PMID- 23143976
TI  - Regulation of tumor cell dormancy by tissue microenvironments and autophagy.
AB  - The development of metastasis is the major cause of death in cancer patients. In
      certain instances, this occurs shortly after primary tumor detection and
      treatment, indicating these lesions were already expanding at the moment of
      diagnosis or initiated exponential growth shortly after. However, in many types
      of cancer, patients succumb to metastatic disease years and sometimes decades
      after being treated for a primary tumor. This has led to the notion that in these
      patients residual disease may remain in a dormant state. Tumor cell dormancy is a
      poorly understood phase of cancer progression and only recently have its
      underlying molecular mechanisms started to be revealed. Important questions that
      remain to be elucidated include not only which mechanisms prevent residual
      disease from proliferating but also which mechanisms critically maintain the long
      term survival of these disseminated residual cells. Herein, we review recent
      evidence in support of genetic and epigenetic mechanisms driving dormancy. We
      also explore how therapy may cause the onset of dormancy in the surviving
      fraction of cells after treatment and how autophagy may be a mechanism that
      maintains the residual cells that are viable for prolonged periods.

PMID- 23143978
TI  - Multifaceted kinetics of immuno-evasion from tumor dormancy.
AB  - Tumor progression is subject to modulation by the immune system. The immune
      system can eliminate tumors or keep them at a dormant equilibrium size, while
      some tumors escape immunomodulation and advance to malignancy. Herein, we discuss
      some aspects of immune evasion of dormant tumors from a theoretical biophysics
      point of view that can be modeled mathematically. We go on to analyze the
      mathematical system on multiple timescales. First, we consider a long timescale
      where tumor evasion is likely due to adaptive (and somewhat deterministic) immuno
      editing. Then, we consider the temporal mesoscale and hypothesize that extrinsic
      noise could be a major factor in induction of immuno-evasion. Implications of
      immuno-evasive mechanisms for the outcome of immunotherapies are also discussed.
      In addition, we discuss the ideas that population level tumor dormancy may not be
      a quiescence phenomenon and that dormant tumors can, at least if modulated by the
      immune system, live a very active and noisy life!

PMID- 23143979
TI  - Tumor dormancy and cancer stem cells: two sides of the same coin?
AB  - Increasing evidence suggests that tumor dormancy represents an important
      mechanism underlying the observed failure of existing therapeutic modalities to
      fully eradicate cancers. In addition to its more established role in maintaining
      minimal residual disease after treatment, dormancy might also critically
      contribute to early stages of tumor development and the formation of clinically
      undetectable micrometastatic foci. There are striking parallels between the
      concept of tumor dormancy and the cancer stem cell (CSC) theory of tumor
      propagation. For instance, the CSC hypothesis similarly predicts that a subset of
      self-renewing cancer cells-that is CSCs-is responsible for tumor initiation,
      bears the preferential ability to survive tumor therapy, and persists long term
      to ultimately cause delayed cancer recurrence and metastatic progression.
      Additionally, many of the biological mechanisms involved in controlling the
      dormant state of a tumor can also govern CSC behavior, including cell cycle
      modifications, alteration of angiogenic processes, and modulation of antitumor
      immune responses. In fact, quiescence and immune escape are emerging hallmark
      features of at least some CSCs, indicating significant overlap between dormant
      cancer populations and CSCs. Herein, we crucially dissect whether CSCs occupy
      specific roles in orchestrating the switch between dormancy and exuberant tumor
      growth. We elucidate how recently uncovered CSC biological features could enable
      these cells to evade immunologic clearance and regulate cancer expansion,
      relapse, and progression. We propose that the study of CSC immunobiological
      pathways holds the promise to critically advance our understanding of the
      processes mediating tumor dormancy. Ultimately, such research endeavors could
      unravel novel therapeutic avenues that efficiently target both proliferating and
      dormant CSCs to minimize the risk of tumor recurrence in cancer patients.

PMID- 23143977
TI  - Tumor dormancy, oncogene addiction, cellular senescence, and self-renewal
      programs.
AB  - Cancers are frequently addicted to initiating oncogenes that elicit aberrant
      cellular proliferation, self-renewal, and apoptosis. Restoration of oncogenes to
      normal physiologic regulation can elicit dramatic reversal of the neoplastic
      phenotype, including reduced proliferation and increased apoptosis of tumor cells
      (Science 297(5578):63-64, 2002). In some cases, oncogene inactivation is
      associated with compete elimination of a tumor. However, in other cases, oncogene
      inactivation induces a conversion of tumor cells to a dormant state that is
      associated with cellular differentiation and/or loss of the ability to self
      replicate. Importantly, this dormant state is reversible, with tumor cells
      regaining the ability to self-renew upon oncogene reactivation. Thus,
      understanding the mechanism of oncogene inactivation-induced dormancy may be
      crucial for predicting therapeutic outcome of targeted therapy. One important
      mechanistic insight into tumor dormancy is that oncogene addiction might involve
      regulation of a decision between self-renewal and cellular senescence. Recent
      evidence suggests that this decision is regulated by multiple mechanisms that
      include tumor cell-intrinsic, cell-autonomous mechanisms and host-dependent,
      tumor cell-non-autonomous programs (Mol Cell 4(2):199-207, 1999; Science
      297(5578):102-104, 2002; Nature 431(7012):1112-1117, 2004; Proc Natl Acad Sci U S
      A 104(32):13028-13033, 2007). In particular, the tumor microenvironment, which is
      known to be critical during tumor initiation (Cancer Cell 7(5):411-423, 2005; J
      Clin Invest 121(6):2436-2446, 2011), prevention (Nature 410(6832):1107-1111,
      2001), and progression (Cytokine Growth Factor Rev 21(1):3-10, 2010), also
      appears to dictate when oncogene inactivation elicits the permanent loss of self
      renewal through induction of cellular senescence (Nat Rev Clin Oncol 8(3):151
      160, 2011; Science 313(5795):1960-1964, 2006; N Engl J Med 351(21):2159-21569,
      2004). Thus, oncogene addiction may be best modeled as a consequence of the
      interplay amongst cell-autonomous and host-dependent programs that define when a
      therapy will result in tumor dormancy.

PMID- 23143980
TI  - Tumor dormancy: long-term survival in a hostile environment.
AB  - Tumor dormancy occurs when cancer cells are present but the tumor does not grow.
      Following treatment, patients may enter complete remission in which persistent
      cells represent the minimal residual disease (MRD). Experimental models and
      clinical data suggest that the absolute quantity of this MRD is extremely low.
      Very few cancer cells can persist for years or decades under these hostile
      conditions that include continuous exposure to maintenance treatment, autologous
      anti-tumor immune response, and a nonpermissive microenvironment. Dormant tumor
      cells may survive despite these destruction factors if they adapt and develop
      strategies to escape from cell death. Escape may result in a state of equilibrium
      between MRD and the patient. Equilibrium between the immune response and tumor
      cells can result in long-term tumor dormancy; however, after variable lengths of
      time, tumor dormancy ends, and the disease progresses. Experimental models have
      shown that dormant tumor cells may over-express B7-H1 and B7.1 and inhibit
      cytotoxic T-cell mediated lysis. This resistance could be therapeutically
      targeted using drugs like MEK inhibitors that modulate pathways involved in B7-H1
      expression. Dormant tumor cells may also develop nonspecific resistance
      mechanisms to cell death, such as deregulation of JAK/STAT and mTORC2/AKT
      pathways or autocrine and paracrine production of cytokines. This deregulation
      leads to cross-resistance between the immune response and cytotoxic drugs,
      indicating that the long-term selection that occurs in vivo during tumor dormancy
      may ultimately result in resistant relapse. Long-term selection of cancer cells
      in vitro using tyrosine kinase inhibitors selects cells that harbor the same
      resistance mechanisms as dormant tumor cells. Elucidating the mechanisms
      underlying the equilibrium that allows for the persistence of dormant tumor cells
      presents a novel strategy for targeted drug treatment in the context of
      maintenance therapy.

PMID- 23143981
TI  - A review of mathematical models of cancer-immune interactions in the context of
      tumor dormancy.
AB  - The role of the immune system in tumor dormancy is now well established. In an
      immune-induced dormant state, potentially lethal cancer cells persist in a state
      where growth is restricted, to little or no increase, by the host's immune
      response. To describe this state in the context of cancer progression and immune
      response, basic temporal (spatially homogeneous) quantitative predator-prey
      constructs are discussed, along with some current and proposed augmentations that
      incorporate potentially significant biological phenomena such as the cancer cell
      transition to a quiescent state or the time delay in T-cell activation. Advances
      in cancer-immune modeling that describe complex interactions underlying the
      ability of the immune system to both promote and inhibit tumor growth are
      emphasized. Finally, the review concludes by discussing future mathematical
      challenges and their biological significance.

PMID- 23143982
TI  - Regulation of tumor dormancy and role of microenvironment: a mathematical model.
AB  - Herein, a mathematical model of a molecular control system for the regulation of
      secondary tumors is formulated and analyzed to explore how secondary tumors can
      be controlled by a primary tumor with/without a surgery and the microenvironment.
      This control system is composed of fibroblast growth factor-2 (FGF2), urokinase
      type plasminogen activator (uPA), plasmin, transforming growth factor-beta
      (TGFbeta), latent TGFbeta (LTGFbeta), and tumor density. The control of secondary
      tumors by primary tumors was first modeled by Boushaba, Nilsen-Hamiton and Levine
      in [46]. The model is based on the idea that the vascularization of a secondary
      tumor can be suppressed by inhibitors from a larger primary tumor. The emergence
      of tumors at secondary sites 5-7 cm from a primary site was observed after
      surgical removal of the primary tumor in silico. The model supports the notion
      that the fate of secondary tumors after surgery depends on the distance from the
      primary tumor and the surrounding microenvironment. As such, the primary tumor
      did not influence the growth of remote secondary tumors, but it could effectively
      suppress the growth of the secondary tumors if they were too close to the primary
      tumor, even after it was removed. Thus, the model predicts the emergence of
      secondary tumors after the excision of the primary tumor when the distance
      between these tumors is in the "distance window." It also predicts that the
      growth behaviors of the secondary tumors depend on the local microenvironment.
      Based on these findings, we propose several treatment options for better clinical
      outcomes.

PMID- 23143983
TI  - Seeing the invisible: how mathematical models uncover tumor dormancy, reconstruct
      the natural history of cancer, and assess the effects of treatment.
AB  - The hypothesis of early metastasis was debated for several decades. Dormant
      cancer cells and surgery-induced acceleration of metastatic growth were first
      observed in clinical studies and animal experiments conducted more than a century
      ago; later, these findings were confirmed in numerous modern studies.In this
      primarily methodological work, we discuss critically important, yet largely
      unobservable, aspects of the natural history of cancer, such as (1) early
      metastatic dissemination; (2) dormancy of secondary tumors; (3) treatment-related
      interruption of metastatic dormancy, induction of angiogenesis, and acceleration
      of the growth of vascular metastases; and (4) the existence of cancer stem cells.
      The hypothesis of early metastasis was debated for several decades. Dormant
      cancer cells and surgery-induced acceleration of metastatic growth were first
      observed in clinical studies and animal experiments conducted more than a century
      ago; later, these findings were confirmed in numerous modern studies.We focus on
      the unique role played by very general mathematical models of the individual
      natural history of cancer that are entirely mechanistic yet, somewhat
      paradoxically, essentially free of assumptions about specific nature of the
      underlying biological processes. These models make it possible to reconstruct in
      considerable detail the individual natural history of cancer and retrospectively
      assess the effects of treatment. Thus, the models can be used as a tool for
      generation and validation of biomedical hypotheses related to carcinogenesis,
      primary tumor growth, its metastatic dissemination, growth of metastases, and the
      effects of various treatment modalities. We discuss in detail one such general
      model and review the conclusions relevant to the aforementioned aspects of cancer
      progression that were drawn from fitting a parametric version of the model to
      data on the volumes of bone metastases in one breast cancer patient and 12
      prostate cancer patients.

PMID- 23143984
TI  - Construction of an all-carbon quaternary stereocenter by the peptide-catalyzed
      asymmetric Michael addition of nitromethane to beta-disubstituted alpha,beta
      unsaturated aldehydes.

PMID- 23143985
TI  - Cumulative exposure to lead and cognition in persons with Parkinson's disease.
AB  - Dementia is an important consequence of Parkinson's disease (PD), with few known
      modifiable risk factors. Cumulative exposure to lead, at levels experienced in
      the community, may exacerbate PD-related neural dysfunction, resulting in
      impaired cognition. Among 101 persons with PD ("cases") and, separately, 50
      persons without PD ("controls"), we evaluated cumulative lead exposure, gauged by
      tibia and patella bone lead concentrations, in relation to cognitive function,
      assessed using a telephone battery developed and validated in a separate sample
      of PD patients. We also assessed the interaction between lead and case-control
      status. After multivariable adjustment, higher tibia bone lead concentration
      among PD cases was associated with worse performance on all of the individual
      telephone tests. In particular, tibia lead levels corresponded to significantly
      worse performance on a telephone analog of the Mini-Mental State Examination and
      tests of working memory and attention. Moreover, higher tibia bone lead
      concentration was associated with significantly worse global composite score
      encompassing all the cognitive tests (P = 0.04). The magnitude of association per
      standard deviation increment in tibia bone lead level was equivalent to the
      difference in global scores among controls in our study, who were approximately 7
      years apart in age. The tibia lead-cognition association was notably stronger
      within cases than within controls (P(difference) = 0.06). Patella bone lead
      concentration was not consistently associated with performance on the tests.
      These data provide evidence suggesting that cumulative exposure to lead may
      result in worsened cognition among persons with PD.

PMID- 23143986
TI  - Prenatal maternal stress affects motor function in 51/2-year-old children:
      project ice storm.
AB  - Evidence suggests that prenatal maternal stress (PNMS) has long-term effects on
      several outcomes, yet effects on neuromotor function are relatively unknown. We
      aimed to determine whether disaster-related PNMS predicts motor functioning in
      young children and whether timing of exposure and sex of the child moderate these
      effects. Objective and subjective PNMS levels were assessed among pregnant women
      exposed to a natural disaster. Their children's bilateral coordination, balance,
      and visual motor integration (VMI) were assessed at 51/2 years. Girls performed
      better than boys. Objective stress exposure and subjective distress interacted
      such that when subjective distress was high, no added effect of objective
      hardship was observed; when subjective distress was low, objective hardship
      showed a negative effect. In girls, late pregnancy exposure was associated with
      poorer outcomes. In conclusion, disaster-related PNMS is associated with
      relatively lower motor functions in exposed offspring. Exposure timing, sex, and
      type of stress influenced the effects.

PMID- 23143988
TI  - Enhancement and modulation of enzymatic activity through higher-order structural
      changes of giant DNA-protein multibranch conjugates.

PMID- 23143987
TI  - MicroRNA-146a-mediated downregulation of IRAK1 protects mouse and human small
      intestine against ischemia/reperfusion injury.
AB  - Intestinal ischemia/reperfusion (I/R) injury causes inflammation and tissue
      damage and is associated with high morbidity and mortality. Uncontrolled
      activation of the innate immune system through toll-like receptors (Tlr) plays a
      key role in I/R-mediated tissue damage but the underlying mechanisms have not
      been fully resolved. Here, we identify post-transcriptional upregulation of the
      essential Tlr signalling molecule interleukin 1 receptor-associated kinase (Irak)
      1 as the causative mechanism for post-ischemic immune hyper-responsiveness of
      intestinal epithelial cells. Increased Irak1 protein levels enhanced epithelial
      ligand responsiveness, chemokine secretion, apoptosis and mucosal barrier
      disruption in an experimental intestinal I/R model using wild-type, Irak1(-/-) 
      and Tlr4(-/-)  mice and ischemic human intestinal tissue. Irak1 accumulation
      under hypoxic conditions was associated with reduced K48 ubiquitination and
      enhanced Senp1-mediated deSUMOylation of Irak1. Importantly, administration of
      microRNA (miR)-146a or induction of miR-146a by the phytochemical
      diindolylmethane controlled Irak1 upregulation and prevented immune hyper
      responsiveness in mouse and human tissue. These findings indicate that Irak1
      accumulation triggers I/R-induced epithelial immune hyper-responsiveness and
      suggest that the induction of miR-146a offers a promising strategy to prevent I/R
      tissue injury.

PMID- 23143989
TI  - Heart rate, heart rate variability and behaviour of horses during air transport.
AB  - Heart rate (HR), HR variability (HRV) and behaviour score (BS) of nine horses
      were evaluated during an eight-hour air transport between The Netherlands and New
      York. HR and HRV parameters were calculated every five minutes during the air
      transport. Compared with transit (40+/-3), mean HRs were higher during loading
      into the jet stall (67+/-21, P<0.001), loading into the aircraft (47+/-6,
      P=0.011), taxiing (50+/-8, P=0.001), and during periods of in-flight turbulence
      (46+/-7, P=0.017). During the flight, individual horses showed differences in
      mean HR (P=0.005) and peak HR (P<0.001). By contrast with HR data, HRV data did
      not differ between stages or horses. BS was highest during turbulence (3.2+/
      0.4). However, behaviour did not always correspond with HR measurements: the
      least responsive horse had the highest HR. Loading into the jet stall caused the
      highest increase in HR and was considered the most stressful event. During
      transit, HR was generally comparable with resting rates. Previous studies have
      shown that loading and transporting by road caused more elevation in HR than
      during loading and transporting by air. HRV data were not found to be useful, and
      caution is needed when interpreting HRV data. Not every horse exhibited stress
      through visible (evasive) behaviour, and HR measurements may provide an
      additional tool to assess stress in horses.

PMID- 23143990
TI  - Advancing our understanding of the pathophysiology of cardiac disease using in
      vivo assessment of heart structure and function in rodent models.

PMID- 23143991
TI  - Effect of acute hypoxia on blood flow in vertebral and internal carotid arteries.
AB  - Hypoxia changes the regional distribution of cerebral blood flow and stimulates
      the ventilatory chemoreflex, thereby reducing CO2 tension. We examined the
      effects of both hypoxia and isocapnic hypoxia on acute changes in internal
      carotid (ICA) and vertebral artery (VA) blood flow. Ten healthy male subjects
      underwent the following two randomly assigned respiratory interventions after a
      resting baseline period with room air: (i) hypoxia; and (ii) isocapnic hypoxia
      with a controlled gas mixture (12% O2; inspiratory mmHg). In the isocapnic
      hypoxia intervention, subjects were instructed to maintain the rate and depth of
      breathing to maintain the level of end-tidal partial pressure of CO2 ( ) during
      the resting baseline period. The ICA and VA blood flow (velocity * cross
      sectional area) were measured using Doppler ultrasonography. The was decreased (
      6.3 +/- 0.9%, P < 0.001) during hypoxia by hyperventilation (minute ventilation
      +12.9 +/- 2.2%, P < 0.001), while was unchanged during isocapnic hypoxia. The ICA
      blood flow was unchanged (P = 0.429), while VA blood flow increased (+10.3 +/-
      3.1%, P = 0.010) during hypoxia. In contrast, isocapnic hypoxia increased both
      ICA (+14.5 +/- 1.4%, P < 0.001) and VA blood flows (+10.9 +/- 2.4%, P < 0.001).
      Thus, hypoxic vasodilatation outweighed hypocapnic vasoconstriction in the VA,
      but not in the ICA. These findings suggest that acute hypoxia elicits an increase
      in posterior cerebral blood flow, possibly to maintain essential homeostatic
      functions of the brainstem.

PMID- 23143992
TI  - Immobilization increases interleukin-6, but not tumour necrosis factor-alpha,
      release from the leg during exercise in humans.
AB  - Data on interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-alpha) release
      during acute exercise are not conclusive, and information is lacking about the
      impact of physical inactivity. Some studies have shown an increase, but others
      report no changes in IL-6 and TNF-alpha release during exercise. We have now
      studied the temporal relationship of leg IL-6 and TNF-alpha release before and
      during isolated two-legged exercise after 14 days of one-leg immobilization (IM)
      while the other leg served as the control (CON) leg. Fifteen healthy male
      subjects (mean +/- SEM age, 23 +/- 1 years; body mass index, 23.6 +/- 0.7 kg m(
      2); and maximal oxygen uptake, 46.8 +/- 1.4 ml kg(-1) min(-1)) performed 45 min
      of two-legged dynamic knee-extensor exercise at 19.6 +/- 0.8 W. Arterial and
      femoral venous blood samples from the CON and the IM leg were collected every 15
      min during exercise, and leg blood flow was measured with Doppler ultrasound. The
      arterial plasma IL-6 concentration increased (P < 0.05) with exercise (rest, 1.3
      +/- 0.1 pg ml(-1); 15 min, 1.9 +/- 0.2 pg ml(-1); 30 min, 2.4 +/- 0.2 pg ml(-1);
      and 45 min, 3.1 +/- 0.3 pg ml(-1)). Interleukin-6 release occurred after 15 min
      of exercise, and the release from the IM leg was significantly greater compared
      with the CON leg after 45 min (1114 +/- 152 versus 606 +/- 14 pg min(-1),
      respectively, P < 0.05). Tumour necrosis factor-alpha release did not differ
      between the CON and the IM leg, and arterial concentrations remained unchanged
      during exercise (P > 0.05). In conclusion, prior immobilization enhances release
      of IL-6 from the leg during exercise at a moderate workload, and the release is
      already present in the early phase of exercise. Neither immobilization nor
      exercise had an effect on TNF-alpha release in the working legs.

PMID- 23143993
TI  - Effects of glutamine supplementation on muscle function and stress responses in a
      mouse model of spinal cord injury.
AB  - Spinal cord injury (SCI) results in loss of muscle function due to rapid
      breakdown of contractile proteins. Glutamine supplementation improves clinical
      outcomes, but its effects on muscle function after SCI are unknown. The benefits
      of glutamine in non-skeletal muscle tissues involve elevated heat shock protein
      (Hsp)70 and Hsp25, but the muscle response may differ because it is the largest
      contributor to plasma glutamine. We tested the hypothesis that glutamine
      preserves muscle function after SCI and that this is associated with increased
      heat shock protein and reduced inflammatory factors, interleukin-6 (IL-6) and
      tumour necrosis factor-alpha (TNFalpha). Changes in plantarflexor force,
      fatigability and total myofibrillar, Hsp70, Hsp25, IL-6 and TNFalpha muscle
      protein levels were measured 7 days after sham or spinal cord transection surgery
      in mice receiving daily placebo or glutamine. Compared with placebo, after SCI
      glutamine significantly attenuated the reductions in maximal isometric force
      (0.22 +/- 0.01 versus 0.31 +/- 0.03 N, respectively) and fatigue resistance (34
      +/- 4 versus 59 +/- 4% of initial force, respectively). Glutamine significantly
      ameliorated the loss of myofibrillar protein with spinal cord transection. Spinal
      cord transection was associated with decreased Hsp70 and Hsp25 with glutamine
      only (45 +/- 3 and 44 +/- 5% of placebo, respectively). Glutamine significantly
      reduced spinal cord transection-associated increases in IL-6 and TNFalpha
      compared with placebo (38 +/- 6 and 37 +/- 8% of placebo, respectively).
      Functionally, early reductions in contractile protein, force and fatigue
      resistance after SCI were reversed with glutamine. Spinal cord transection
      associated reductions in Hsp70, Hsp25, IL-6 and TNFalpha with glutamine versus
      placebo suggest lower stress in the muscle, possibly related to a reduced need to
      produce glutamine. These findings support glutamine as a therapeutic intervention
      to accelerate recovery of muscle function after SCI.

PMID- 23143994
TI  - Deficiency in pulmonary surfactant proteins in mice with fatty acid binding
      protein 4-Cre-mediated knockout of the tuberous sclerosis complex 1 gene.
AB  - Tuberous sclerosis complex 1 (TSC1) forms a heterodimmer with tuberous sclerosis
      complex 2, to inhibit signalling by the mammalian target of rapamycin (mTOR)
      complex 1 (mTORC1). The mTORC1 stimulates cell growth by promoting anabolic
      cellular processes, such as gene transcription and protein translation, in
      response to growth factors and nutrient signals. Originally designed to test the
      role of TSC1 in adipocyte function, mice in which the gene for TSC1 was
      specifically deleted by the fatty acid binding protein 4 (FABP4)-Cre (Fabp4
      Tsc1cKO mice) died prematurely within 48 h after birth. The Fabp4-Tsc1cKO mouse
      revealed a much smaller phenotype relative to the wild-type littermates. Maternal
      administration of rapamycin, a classical mTOR inhibitor, significantly increased
      the survival time of Fabp4-Tsc1cKO mice for up to 23 days. Both macroscopic and
      microscopic haemorrhages were observed in the lungs of Fabp4-Tsc1cKO mice, while
      other tissues showed no significant changes. Levels of surfactant proteins A and
      B demonstrated a significant decrease in the Fabp4-Tsc1cKO mice, which was
      rescued by maternal injection of rapamycin. Co-localization of FABP4 or TSC1 with
      surfactant protein B was also detected in neonatal pulmonary tissues. Our study
      suggests that TSC1-mTORC1 may be critical for the synthesis of surfactant
      proteins A and B.

PMID- 23143996
TI  - Molybdenum boride and carbide catalyze hydrogen evolution in both acidic and
      basic solutions.

PMID- 23143995
TI  - Regulatory T-lymphocytes mediate amyotrophic lateral sclerosis progression and
      survival.
AB  - In amyotrophic lateral sclerosis (ALS) mice, regulatory T-lymphocytes (Tregs) are
      neuroprotective, slowing disease progression. To address whether Tregs and FoxP3,
      a transcription factor required for Treg function, similarly influence
      progression rates of ALS patients, T-lymphocytes from patients were assessed by
      flow cytometry. Both numbers of Tregs and their FoxP3 protein expressions were
      reduced in rapidly progressing ALS patients and inversely correlated with
      progression rates. The mRNA levels of FoxP3, TGF-beta, IL4 and Gata3, a Th2
      transcription factor, were reduced in rapidly progressing patients and inversely
      correlated with progression rates. Both FoxP3 and Gata3 were accurate indicators
      of progression rates. No differences in IL10, Tbx21, a Th1 transcription factor
      or IFN-gamma expression were found between slow and rapidly progressing patients.
      A 3.5-year prospective study with a second larger cohort revealed that early
      reduced FoxP3 levels were indicative of progression rates at collection and
      predictive of future rapid progression and attenuated survival. Collectively,
      these data suggest that Tregs and Th2 lymphocytes influence disease progression
      rates. Importantly, early reduced FoxP3 levels could be used to identify rapidly
      progressing patients.

PMID- 23143997
TI  - What's wrong with enhancements?

PMID- 23143998
TI  - Commentary on Singh: Not robots: children's perspectives on authenticity, moral
      agency and stimulant drug treatments.

PMID- 23143999
TI  - Experimental reappraisal of continuous dopaminergic stimulation against L-dopa
      induced dyskinesia.

PMID- 23144000
TI  - Tribenzotriquinacene: a versatile synthesis and C3-chiral platforms.

PMID- 23144001
TI  - Real-time fluorescence turn-on detection of alkaline phosphatase activity with a
      novel perylene probe.
AB  - A tetracationic perylene probe (probe 1) was designed and synthesized. Probe 1
      was used for the real-time fluorescence turn-on assay of alkaline phosphatase
      (ALP) activity and inhibitor screening. Probe 1 monomer fluorescence could be
      very efficiently quenched by ATP through the formation of an ATP/probe 1 complex.
      ALP triggered the degradation of ATP, the breakdown of the ATP/probe 1 complex,
      and the recovery of the probe 1 monomer fluorescence. In the presence of an ALP
      inhibitor, a decrease in fluorescence recovery was observed.

PMID- 23144002
TI  - Parkinson's disease patients show reduced cortical-subcortical sensorimotor
      connectivity.
AB  - Reduced dopamine input to cortical and subcortical brain structures, particularly
      those in the sensorimotor network, is a hallmark of Parkinson's disease (PD). The
      extent to which dopamine dysfunction affects connectivity within this and other
      brain networks remains to be investigated. The purpose of this study was to
      measure anatomical and functional connectivity in groups of PD patients and
      controls to determine whether connectivity deficits within the cortico-basal
      ganglia thalamocortical system could be attributed to PD, particularly in
      sensorimotor connections. A neuroimaging paradigm involving diffusion-weighted
      magnetic resonance imaging (MRI) and resting-state functional MRI was implemented
      in a large cohort of PD patients and control subjects. Probabilistic tractography
      and functional correlation analyses were performed to map connections between
      brain structures and to derive indices of connectivity that were then used to
      compare groups. Anatomical connectivity deficits were demonstrated in PD
      patients, specifically for sensorimotor connections. Functional deficits were
      also found in some of the same connections. In addition, functional connectivity
      was found to increase in associative and limbic connections in PD patients
      compared with controls. This study lends support to findings regarding the
      dysfunction of the sensorimotor circuit in PD. As deficits in anatomical and
      functional connectivity within this circuit were in some cases concordant in PD
      patients, a possible link between brain structure and function is suggested.
      Increases in functional connectivity in other cortico-basal ganglia
      thalamocortical circuits may be indicative of compensatory effects in response to
      system deficits elsewhere.

PMID- 23144003
TI  - Low pathogenic avian influenza H7N7 in domestic poultry in Germany in 2011.

PMID- 23144004
TI  - Enhancing the photocatalytic activity of anatase TiO2 by improving the specific
      facet-induced spontaneous separation of photogenerated electrons and holes.
AB  - Recently, it has been proven that directional flow of photogenerated charge
      carriers occurs on specific facets of TiO(2)  nanocrystals. Herein, we
      demonstrate that the photocatalytic activity of anatase TiO(2)  nanocrystals in
      both photoreduction and photooxidation processes can be enhanced by selectively
      depositing Pt nanoparticles on the {101} facets, which strengthens spontaneously
      surface-induced separation between photogenerated electrons and holes in the
      photocatalysis process. An optimal ratio of the oxidative {001} facets to the
      reductive {101} facets exists with regard to the photocatalysis of the faceted
      TiO(2)  nanocrystals, and this is crucial for balancing the recombination and
      redox reaction rates of photogenerated electrons and holes. The present work
      might help us gain deeper insight into the relation between the specific surface
      of semiconductor photocatalysts and their photocatalytic activities and provides
      us with a new route to design photocatalysts with high photocatalytic activity.

PMID- 23144005
TI  - Quantifying analytes in paper-based microfluidic devices without using external
      electronic readers.

PMID- 23144006
TI  - 1-Hz repetitive transcranial magnetic stimulation and diphasic dyskinesia in
      Parkinson's disease.

PMID- 23144007
TI  - A novel approach to standardised recording of bleeding in a high risk neonatal
      population.
AB  - BACKGROUND: Bleeding assessment tools have been developed in other specialties to
      standardise the recording of bleeding for clinical haemostatic outcomes in
      transfusion trials, but such tools have not been developed for routine use in
      neonatology. AIM: The objective of this study was to develop, refine and evaluate
      a neonatal bleeding assessment tool (NeoBAT) to standardise the clinical
      recording of bleeding in premature and term neonates in an intensive care
      setting. METHODS: This prospective neonatal international multicentre study
      included all episodes of bleeding in infants admitted to the intensive/high
      dependency care nursery over a 2-4-week period. The NeoBAT was developed to
      record neonatal bleeding episodes. We tested its reliability and reproducibility
      with duplicate assessments. RESULTS: Duplicate assessments revealed 98%
      concordance. Bleeding occurred in 25% (37/146) of infants overall and was most
      common in preterm infants. 11% (16/146) infants had major/severe bleeds, 1%
      (2/146) moderate and 13% (19/146) minor bleeds. CONCLUSIONS: Bleeding is common
      in premature and term neonates admitted to intensive/high dependency care
      nurseries. This novel bleeding assessment tool facilitates prospective recording
      of bleeding events in neonatal intensive care settings and may allow standardised
      bleeding assessments in this high risk population.

PMID- 23144008
TI  - Benchmarking in neonatal intensive care: obstetrical and neonatal practices and
      registration policies may influence outcome data.

PMID- 23144009
TI  - Low-dose aspirin is associated with an increased risk of haemorrhage; but not in
      people with diabetes who have a high baseline rate of bleeding.
AB  - Implications for practice and research: Low-dose aspirin (<= 300 mg/day)
      increases the risk of major bleeding. Individuals with diabetes have a higher
      risk of bleeding independent of aspirin exposure. Future work should include
      comparative effectiveness studies to help inform treatment strategies based on
      individual risks, benefits, patient preferences and values.

PMID- 23144010
TI  - Higher nurse staffing levels associated with reductions in unplanned readmissions
      to intensive care or operating theatre, and in postoperative in-hospital
      mortality in heart surgery patients.
AB  - Implications for practice and research: Higher nurse staffing levels for
      postoperative care of cardiac surgery patients reduces the risk of unplanned re
      admission to the intensive care or operating theatre and in-hospital mortality.
      Larger international studies are needed to assess the effect of nurse staffing
      levels and risk of hospital-wide adverse events.

PMID- 23144011
TI  - A depression screening tool finds that 54% of acute cardiac patients are at risk
      of depression; use of the tool improves documentation and referral.
AB  - Implications for practice and research: This study found that nurses on
      cardiovascular care units were able to administer depression screening tools and
      document referral activities for positive screens. It is not known whether
      depression screening improved depression outcomes. Evidence of benefits in excess
      of harms, established by well-conducted randomised controlled trials (RCTs) of
      depression screening interventions, is needed before depression screening is
      implemented in cardiovascular care settings.

PMID- 23144012
TI  - Asking next-of-kin of recently deceased cancer patients to take part in research:
      11 of 20 surveyed found it a positive experience.
AB  - Implications for practice and research: These results will aid the development of
      protocols for screening bereaved individuals who are eligible for study
      participation. These results provide insight into bereaved participants'
      preferences for data collection methods (e.g., face-to-face, phone and self
      completion postal surveys). The needs of non-cancer-related deaths and paediatric
      populations (e.g., bereaved child participants; childhood deaths) need
      consideration in future studies.

PMID- 23144013
TI  - Mono-PEGylated zinc(II) phthalocyanines: preparation, nanoparticle formation, and
      in vitro photodynamic activity.

PMID- 23144014
TI  - Elective ventilation and the politics of death.
AB  - This essay comments on the British Medical Association's recent suggestion that
      protocols for Elective Ventilation (EV) might be revived in order to increase the
      number of viable organs available for transplant. I suggest that the proposed
      revival results, at least in part, from developments in the contemporary
      political landscape, notably the decreasing likelihood of an opt-out system for
      the UK's Organ Donor Register. I go on to suggest that EV is unavoidably situated
      within complex debates surrounding the epistemology and ontology of death. Such
      questions cannot be settled a priori by medical science, bioethics or
      philosophical reflection. As Radcliffe-Richards suggests, the determination of
      death has become a moral question, and therefore, now extends into the political
      arena. I argue for the conclusion that EV, and wider debates about organ donation
      and the constitution of the organ donation register, are matters of
      'biocitizenship' and must, therefore, be addressed as 'biopolitical' questions.

PMID- 23144015
TI  - Translation and cross-cultural adaptation of a family booklet on comfort care in
      dementia: sensitive topics revised before implementation.
AB  - INTRODUCTION: Families of patients with dementia may need support in difficult
      end-of-life decision making. Such guidance may be culturally sensitive. METHODS:
      To support families in Canada, a booklet was developed to aid decision making on
      palliative care issues. For reasons of cost effectiveness and promising effects,
      we prepared for its implementation in Italy, the Netherlands and Japan. Local
      teams translated and adapted the booklet to local ethical, legal and medical
      standards where needed, retaining guidance on palliative care. Using qualitative
      content analyses, we grouped and compared adaptations to understand culturally
      sensitive aspects. RESULTS: Three themes emerged: (1) relationships among
      patient, physician and other professionals-the authority of the physician was
      more explicit in adapted versions; (2) patient rights and family position-adding
      detail about local regulations; and (3) typology of treatments and decisions.
      Considerations underlying palliative care decisions were detailed (Dutch and
      Italian versions), and the Japanese version frequently referred to professional
      and legal standards, and life-prolongation was a competing goal. Text on
      artificial feeding or fluids and euthanasia was revised extensively. CONCLUSIONS:
      Providing artificial feeding and fluids and discussing euthanasia may be
      particularly sensitive topics, and guidance on these subjects needs careful
      consideration of ethical aspects and possible adaptations to local standards and
      practice. The findings may promote cross-national debate on sensitive, core
      issues regarding end-of-life care in dementia.

PMID- 23144016
TI  - Fastest thermal isomerization of an azobenzene for nanosecond photoswitching
      applications under physiological conditions.

PMID- 23144019
TI  - Chronic abdominal pain in children: help in spotting the organic diagnosis.

PMID- 23144020
TI  - Preferential formation of cyclic trimers by palladium-catalyzed oxidative
      coupling reactions of 2,18-diethynylporphyrins.

PMID- 23144021
TI  - Hypoxia and PGE(2) regulate MiTF-CX during cervical ripening.
AB  - The mechanisms by which the cervix remains closed during the massive uterine
      expansion of pregnancy are unknown. IL-8 is important for recruitment of immune
      cells into the cervical stroma, matrix remodeling, and dilation of the cervix
      during labor. Previously, we have shown that several cytokine genes
      transcriptionally repressed in the cervix during gestation are activated during
      cervical ripening and dilation. IL-8 gene expression is repressed in cervical
      stromal cells during pregnancy by the transcription factor microphthalmia
      associated transcription factor (MiTF-CX). Here, we tested the hypothesis that
      hypoxia and the transcription factor hypoxia inducible factor-1alpha (HIF-1alpha)
      may regulate MiTF-CX and cervical ripening. Using tissues from women during
      pregnancy before and after cervical ripening, we show that, during cervical
      ripening, HIF-1alpha was stabilized and relocalized to the nucleus. Further, we
      found that hypoxia and two hypoxia mimetics that stabilize HIF-1alpha activated
      the transcriptional repressor differentiated embryo chondrocyte-expressed gene 1,
      which bound to sites in the MiTF-CX promoter crucial for its positive
      autoregulation. Ectopic overexpression of MiTF-CX abrogated hypoxia-induced up
      regulation of IL-8 gene expression. We also show that activation of HIF-1alpha
      induced cyclooxygenase-2 and that prostaglandin E(2) repressed MiTF-CX. We
      conclude that hypoxia and stabilization of the transcription factor HIF-1alpha
      result in up-regulation of differentiated embryo chondrocyte-expressed gene 1,
      loss of MiTF, and absence of MiTF binding to the IL-8 promoter, which in turn
      leads to up-regulation of IL-8 gene expression. Hypoxia also up-regulated
      cyclooxygenase-2, leading to prostaglandin E(2)-mediated loss of MiTF in cervical
      stromal cells. The results support a pivotal role for hypoxia and HIF-1alpha in
      the cervical ripening process during pregnancy.

PMID- 23144022
TI  - He's a real man: a qualitative study of the social context of couples' vasectomy
      decisions among a racially diverse population.
AB  - Vasectomy has advantages with respect to safety and cost when compared with
      female sterilization. The reasons underlying the overall low use of vasectomy,
      particularly among Black and Latinos, have not been adequately explored. The
      goals of this study were to (a) explore the social context of vasectomy decisions
      and (b) generate hypotheses about the social factors contributing to differences
      in vasectomy use by race/ethnicity. Fourteen group and nine couples interviews
      were conducted. Participants were 37 heterosexual couples aged 25 to 55 years who
      had reached their desired family size and self-identified as Black, Latino, or
      White. Participants discussed reasons that men and women would or would not
      select male sterilization. Reasons to select vasectomy included a desire to care
      for their current family, sharing contraceptive responsibility, and infidelity.
      Reasons not to select vasectomy included negative associations with the term
      sterilization, loss of manhood, and permanence. Misconceptions about vasectomy
      included misunderstandings about the vasectomy procedure and adverse
      postvasectomy sexual function. In addition, Black and Latino participants cited
      perceived ease of reversibility of female sterilization and lack of support
      around vasectomy as reasons not to choose it. Improving communication and social
      support for vasectomy, particularly among Black and Latino communities, may
      improve vasectomy utilization. Misconceptions regarding female and male
      sterilization should be targeted in counseling sessions to ensure men, women, and
      couples are making informed contraceptive decisions.

PMID- 23144023
TI  - Tissue classification using ultrasound-induced variations in acoustic
      backscattering features.
AB  - Ultrasound (US) radio-frequency (RF) time series is an effective tissue
      classification method that enables accurate cancer diagnosis, but the mechanisms
      underlying this method are not completely understood. This paper presents a model
      to describe the variations in tissue temperature and sound speed that take place
      during the RF time series scanning procedures and relate these variations to US
      backscattering. The model was used to derive four novel characterization
      features. These features were used to classify three animal tissues, and they
      obtained accuracies as high as 88.01%. The performance of the proposed features
      was compared with RF time series features proposed in a previous study. The
      results indicated that the US-induced variations in tissue temperature and sound
      speed, which were used to derive the proposed features, were important
      contributors to the tissue typing capabilities of the RF time series. Simulations
      carried out to estimate the heating induced during the scanning procedure
      employed in this study showed temperature rises lower than 2  degrees C. The
      model and results presented in this paper can be used to improve the RF time
      series.

PMID- 23144024
TI  - Elastic light single-scattering spectroscopy for the detection of cervical
      precancerous ex vivo.
AB  - Potential application of elastic light single-scattering spectroscopy (ELSSS) for
      differentiating high-grade squamous intraepithelial lesions (HSIL) from non-HSIL
      tissues was investigated. An ELSSS system was used to acquire spectra from cervix
      tissues. A single-fiber optical probe with a diameter of 100 MUm was used for
      both delivery and detection of white light to and from the cervix tissue.
      Spectroscopic measurements were acquired from 95 ex vivo biopsy samples of 60 pap
      smear positive patients and normal cervix tissue from 10 patients after
      hysterectomy were used as a negative control group. Spectroscopic results of 95
      cervix biopsy were compared to the histopathology of the biopsy samples.
      Sensitivity and specificity of the ELSSS system in the differentiation of HSIL
      and non-HSIL tissues are 87.5% and 45.6%, respectively, for the pap smear and
      colposcopy positive biopsy samples. The ELSSS system has the potential for use in
      real-time diagnosis of HSIL tissues as an adjunct to Papanicolaou test (pap
      smear) and colposcopy.

PMID- 23144025
TI  - Introducing Willmore flow into level set segmentation of spinal vertebrae.
AB  - Segmentation of spinal vertebrae in 3-D space is a crucial step in the study of
      spinal related disease or disorders. However, the complexity of vertebrae shapes,
      with gaps in the cortical bone and boundaries, as well as noise, inhomogeneity,
      and incomplete information in images, has made spinal vertebrae segmentation a
      difficult task. In this paper, we introduce a new method for an accurate spinal
      vertebrae segmentation that is capable of dealing with noisy images with missing
      information. This is achieved by introducing an edge-mounted Willmore flow, as
      well as a prior shape kernel density estimator, to the level set segmentation
      framework. While the prior shape model provides much needed prior knowledge when
      information is missing from the image, and draws the level set function toward
      prior shapes, the edge-mounted Willmore flow helps to capture the local geometry
      and smoothes the evolving level set surface. Evaluation of the segmentation
      results with ground-truth validation demonstrates the effectiveness of the
      proposed approach: an overall accuracy of  89.32+/-1.70% and  14.03+/-1.40 mm are
      achieved based on the Dice similarity coefficient and Hausdorff distance,
      respectively, while the inter- and intraobserver variation agreements are 
      92.11+/-1.97%, 94.94+/-1.69%, 3.32+/-0.46, and  3.80+/-0.56 mm.

PMID- 23144026
TI  - Robust alignment of prostate histology slices with quantified accuracy.
AB  - No current imaging technique is capable of detecting with precision tumors in the
      prostate. To evaluate each technique, the histology data must be precisely mapped
      to the imaged data. As the histology slices cannot be assumed to be cut along the
      same plane as the imaged data were acquired, the registration must be considered
      as a 3-D problem. This requires the prior alignment of the histology slices. We
      propose a protocol in which three needles are inserted into the fresh prostate,
      creating internal fiducial markers visible in the histology slices. Our algorithm
      then automatically detects and identifies these markers, enabling the automatic
      rigid alignment of each slice. The accuracy of the algorithm was quantified in
      simulated images, a beef liver sample in which a validation marker had been
      created, and ten prostate specimens. The simulated images showed that the
      algorithm has no associated residual error for a situation where there is no
      deformation. In the beef liver images, the average accuracy of the alignment was
      0.12 +/- 0.09 mm at the fiducial markers, and 0.62 +/- 0.46 mm at a validation
      marker positioned approximately 20 mm from the fiducial markers. Concerning the
      ten prostates, there were 19.2 histology slices on average per specimen. On
      average, 93.7% of the fiducial markers created were visible in the slices, of
      which 96.1% were then automatically and correctly detected and identified,
      enabling an alignment of average accuracy 0.18 +/- 0.13 mm at the fiducial
      markers. As a cancer of volume <0.5 cm(3) is classified as clinically
      insignificant, the accuracy achieved justified the choice of a rigid
      registration. An attractive feature of this method is the time required, less
      than 6 min on average per prostate specimen.

PMID- 23144027
TI  - Design and performance evaluation of a minimally invasive telerobotic platform
      for transurethral surveillance and intervention.
AB  - Bladder cancer, a significant cause of morbidity and mortality worldwide,
      presents a unique opportunity for aggressive treatment due to the ease of
      transurethral accessibility. While the location affords advantages, transurethral
      resection of bladder tumors can pose a difficult challenge for surgeons
      encumbered by current instrumentation or difficult anatomic tumor locations. This
      paper presents the design and evaluation of a telerobotic system for
      transurethral surveillance and surgical intervention. The implementation seeks to
      improve current procedures and enable development of new surgical techniques by
      providing a platform for intravesicular dexterity and integration of novel
      imaging and interventional instrumentation. The system includes a dexterous
      continuum robot with access channels for the parallel deployment of multiple
      visualization and surgical instruments. This paper first presents the clinical
      conditions imposed by transurethral access and the limitations of the current
      state-of-the-art instrumentation. Motivated by the clinical requirements, the
      design considerations for this system are discussed and the prototype system is
      presented. Telemanipulation evaluation demonstrates submillimetric RMS
      positioning accuracy and intravesicular dexterity suitable for improving
      transurethral surveillance and intervention.

PMID- 23144028
TI  - Compressed sensing for energy-efficient wireless telemonitoring of noninvasive
      fetal ECG via block sparse Bayesian learning.
AB  - Fetal ECG (FECG) telemonitoring is an important branch in telemedicine. The
      design of a telemonitoring system via a wireless body area network with low
      energy consumption for ambulatory use is highly desirable. As an emerging
      technique, compressed sensing (CS) shows great promise in
      compressing/reconstructing data with low energy consumption. However, due to some
      specific characteristics of raw FECG recordings such as nonsparsity and strong
      noise contamination, current CS algorithms generally fail in this application.
      This paper proposes to use the block sparse Bayesian learning framework to
      compress/reconstruct nonsparse raw FECG recordings. Experimental results show
      that the framework can reconstruct the raw recordings with high quality.
      Especially, the reconstruction does not destroy the interdependence relation
      among the multichannel recordings. This ensures that the independent component
      analysis decomposition of the reconstructed recordings has high fidelity.
      Furthermore, the framework allows the use of a sparse binary sensing matrix with
      much fewer nonzero entries to compress recordings. Particularly, each column of
      the matrix can contain only two nonzero entries. This shows that the framework,
      compared to other algorithms such as current CS algorithms and wavelet
      algorithms, can greatly reduce code execution in CPU in the data compression
      stage.

PMID- 23144029
TI  - The transesophageal echocardiography simulator based on computed tomography
      images.
AB  - Simulators are a new tool in education in many fields, including medicine, where
      they greatly improve familiarity with medical procedures, reduce costs, and,
      importantly, cause no harm to patients. This is so in the case of transesophageal
      echocardiography (TEE), in which the use of a simulator facilitates spatial
      orientation and helps in case studies. The aim of the project described in this
      paper is to simulate an examination by TEE. This research makes use of available
      computed tomography data to simulate the corresponding echocardiographic view.
      This paper describes the essential characteristics that distinguish these two
      modalities and the key principles of the wave phenomena that should be considered
      in the simulation process, taking into account the conditions specific to the
      echocardiography. The construction of the CT2TEE (Web-based TEE simulator) is
      also presented. The considerations include ray-tracing and ray-casting techniques
      in the context of ultrasound beam and artifact simulation. An important aspect of
      the interaction with the user is raised.

PMID- 23144030
TI  - A robust ultrashort TE (UTE) imaging method with corrected k-space trajectory by
      using parametric multiple function model of gradient waveform.
AB  - Ultra-short TE (UTE) sequences with radial sampling make it possible to visualize
      tissues with very short T2 decay times. The UTE sequence acquires an echo signal
      from the central to the outer parts of k-space and is very sensitive to small
      trajectory errors. Therefore, k-space errors caused by imperfections in the
      gradient system performance, such as gradient delay and waveform distortion, must
      be corrected. During normal clinical use, these errors must be corrected to
      account for any gradient strength, or image obliquity. Because of time limitation
      on clinical examination, a simple, robust, and time-efficient correction method
      for use with UTE is needed. We demonstrated image degradation due to k-space
      errors by simulation and found that uncontrolled gradient time delays were the
      dominant cause of image degradation. They could be corrected by using a pre-scan
      calibration that works by comparison of half and full echo signals. Further
      improvements in image quality were achieved by using a one-time calibration of
      gradient waveform approximations that were built from multiple exponential
      functions and were used during image reconstruction. We have developed a robust
      UTE correction method that consists of a gradient waveform approximation that
      follows a short pre-scan for estimating gradient time delay errors.

PMID- 23144031
TI  - Flip-invariant SIFT for copy and object detection.
AB  - Scale-invariant feature transform (SIFT) feature has been widely accepted as an
      effective local keypoint descriptor for its invariance to rotation, scale, and
      lighting changes in images. However, it is also well known that SIFT, which is
      derived from directionally sensitive gradient fields, is not flip invariant. In
      real-world applications, flip or flip-like transformations are commonly observed
      in images due to artificial flipping, opposite capturing viewpoint, or symmetric
      patterns of objects. This paper proposes a new descriptor, named flip-invariant
      SIFT (or F-SIFT), that preserves the original properties of SIFT while being
      tolerant to flips. F-SIFT starts by estimating the dominant curl of a local patch
      and then geometrically normalizes the patch by flipping before the computation of
      SIFT. We demonstrate the power of F-SIFT on three tasks: large-scale video copy
      detection, object recognition, and detection. In copy detection, a framework,
      which smartly indices the flip properties of F-SIFT for rapid filtering and weak
      geometric checking, is proposed. F-SIFT not only significantly improves the
      detection accuracy of SIFT, but also leads to a more than 50% savings in
      computational cost. In object recognition, we demonstrate the superiority of F
      SIFT in dealing with flip transformation by comparing it to seven other
      descriptors. In object detection, we further show the ability of F-SIFT in
      describing symmetric objects. Consistent improvement across different kinds of
      keypoint detectors is observed for F-SIFT over the original SIFT.

PMID- 23144032
TI  - Shape sparse representation for joint object classification and segmentation.
AB  - In this paper, a novel variational model based on prior shapes for simultaneous
      object classification and segmentation is proposed. Given a set of training
      shapes of multiple object classes, a sparse linear combination of training shapes
      in a low-dimensional representation is used to regularize the target shape in
      variational image segmentation. By minimizing the proposed variational
      functional, the model is able to automatically select the reference shapes that
      best represent the object by sparse recovery and accurately segment the image,
      taking into account both the image information and the shape priors. For some
      applications under an appropriate size of training set, the proposed model allows
      artificial enlargement of the training set by including a certain number of
      transformed shapes for transformation invariance, and then the model remains
      jointly convex and can handle the case of overlapping or multiple objects
      presented in an image within a small range. Numerical experiments show promising
      results and the potential of the method for object classification and
      segmentation.

PMID- 23144033
TI  - Multiscale image fusion using the undecimated wavelet transform with spectral
      factorization and nonorthogonal filter banks.
AB  - Multiscale transforms are among the most popular techniques in the field of pixel
      level image fusion. However, the fusion performance of these methods often
      deteriorates for images derived from different sensor modalities. In this paper,
      we demonstrate that for such images, results can be improved using a novel
      undecimated wavelet transform (UWT)-based fusion scheme, which splits the image
      decomposition process into two successive filtering operations using spectral
      factorization of the analysis filters. The actual fusion takes place after
      convolution with the first filter pair. Its significantly smaller support size
      leads to the minimization of the unwanted spreading of coefficient values around
      overlapping image singularities. This usually complicates the feature selection
      process and may lead to the introduction of reconstruction errors in the fused
      image. Moreover, we will show that the nonsubsampled nature of the UWT allows the
      design of nonorthogonal filter banks, which are more robust to artifacts
      introduced during fusion, additionally improving the obtained results. The
      combination of these techniques leads to a fusion framework, which provides clear
      advantages over traditional multiscale fusion approaches, independent of the
      underlying fusion rule, and reduces unwanted side effects such as ringing
      artifacts in the fused reconstruction.

PMID- 23144034
TI  - Context-dependent logo matching and recognition.
AB  - We contribute, through this paper, to the design of a novel variational framework
      able to match and recognize multiple instances of multiple reference logos in
      image archives. Reference logos and test images are seen as constellations of
      local features (interest points, regions, etc.) and matched by minimizing an
      energy function mixing: 1) a fidelity term that measures the quality of feature
      matching, 2) a neighborhood criterion that captures feature co
      occurrence/geometry, and 3) a regularization term that controls the smoothness of
      the matching solution. We also introduce a detection/recognition procedure and
      study its theoretical consistency. Finally, we show the validity of our method
      through extensive experiments on the challenging MICC-Logos dataset. Our method
      overtakes, by 20%, baseline as well as state-of-the-art matching/recognition
      procedures.

PMID- 23144035
TI  - Efficient contrast enhancement using adaptive gamma correction with weighting
      distribution.
AB  - This paper proposes an efficient method to modify histograms and enhance contrast
      in digital images. Enhancement plays a significant role in digital image
      processing, computer vision, and pattern recognition. We present an automatic
      transformation technique that improves the brightness of dimmed images via the
      gamma correction and probability distribution of luminance pixels. To enhance
      video, the proposed image-enhancement method uses temporal information regarding
      the differences between each frame to reduce computational complexity.
      Experimental results demonstrate that the proposed method produces enhanced
      images of comparable or higher quality than those produced using previous state
      of-the-art methods.

PMID- 23144036
TI  - Comments on "A robust fuzzy local information C-means clustering algorithm".
AB  - In a recent paper, Krinidis and Chatzis proposed a variation of fuzzy c-means
      algorithm for image clustering. The local spatial and gray-level information are
      incorporated in a fuzzy way through an energy function. The local minimizers of
      the designed energy function to obtain the fuzzy membership of each pixel and
      cluster centers are proposed. In this paper, it is shown that the local
      minimizers of Krinidis and Chatzis to obtain the fuzzy membership and the cluster
      centers in an iterative manner are not exclusively solutions for true local
      minimizers of their designed energy function. Thus, the local minimizers of
      Krinidis and Chatzis do not converge to the correct local minima of the designed
      energy function not because of tackling to the local minima, but because of the
      design of energy function.

PMID- 23144037
TI  - Exponential local discriminant embedding and its application to face recognition.
AB  - Local discriminant embedding (LDE) has been recently proposed to overcome some
      limitations of the global linear discriminant analysis method. In the case of a
      small training data set, however, LDE cannot directly be applied to high
      dimensional data. This case is the so-called small-sample-size (SSS) problem. The
      classical solution to this problem was applying dimensionality reduction on the
      raw data (e.g., using principal component analysis). In this paper, we introduce
      a novel discriminant technique called "exponential LDE" (ELDE). The proposed ELDE
      can be seen as an extension of LDE framework in two directions. First, the
      proposed framework overcomes the SSS problem without discarding the discriminant
      information that was contained in the null space of the locality preserving
      scatter matrices associated with LDE. Second, the proposed ELDE is equivalent to
      transforming original data into a new space by distance diffusion mapping
      (similar to kernel-based nonlinear mapping), and then, LDE is applied in such a
      new space. As a result of diffusion mapping, the margin between samples belonging
      to different classes is enlarged, which is helpful in improving classification
      accuracy. The experiments are conducted on five public face databases: Yale,
      Extended Yale, PF01, Pose, Illumination, and Expression (PIE), and Facial
      Recognition Technology (FERET). The results show that the performances of the
      proposed ELDE are better than those of LDE and many state-of-the-art discriminant
      analysis techniques. 

PMID- 23144038
TI  - Optimal Selection of Parameters for Nonuniform Embedding of Chaotic Time Series
      Using Ant Colony Optimization.
AB  - The optimal selection of parameters for time-delay embedding is crucial to the
      analysis and the forecasting of chaotic time series. Although various parameter
      selection techniques have been developed for conventional uniform embedding
      methods, the study of parameter selection for nonuniform embedding is progressed
      at a slow pace. In nonuniform embedding, which enables different dimensions to
      have different time delays, the selection of time delays for different dimensions
      presents a difficult optimization problem with combinatorial explosion. To solve
      this problem efficiently, this paper proposes an ant colony optimization (ACO)
      approach. Taking advantage of the characteristic of incremental solution
      construction of the ACO, the proposed ACO for nonuniform embedding (ACO-NE)
      divides the solution construction procedure into two phases, i.e., selection of
      embedding dimension and selection of time delays. In this way, both the embedding
      dimension and the time delays can be optimized, along with the search process of
      the algorithm. To accelerate search speed, we extract useful information from the
      original time series to define heuristics to guide the search direction of ants.
      Three geometry- or model-based criteria are used to test the performance of the
      algorithm. The optimal embeddings found by the algorithm are also applied in time
      series forecasting. Experimental results show that the ACO-NE is able to yield
      good embedding solutions from both the viewpoints of optimization performance and
      prediction accuracy. 

PMID- 23144039
TI  - Efficient shortest-path-tree computation in network routing based on pulse
      coupled neural networks.
AB  - Shortest path tree (SPT) computation is a critical issue for routers using link
      state routing protocols, such as the most commonly used open shortest path first
      and intermediate system to intermediate system. Each router needs to recompute a
      new SPT rooted from itself whenever a change happens in the link state. Most
      commercial routers do this computation by deleting the current SPT and building a
      new one using static algorithms such as the Dijkstra algorithm at the beginning.
      Such recomputation of an entire SPT is inefficient, which may consume a
      considerable amount of CPU time and result in a time delay in the network. Some
      dynamic updating methods using the information in the updated SPT have been
      proposed in recent years. However, there are still many limitations in those
      dynamic algorithms. In this paper, a new modified model of pulse-coupled neural
      networks (M-PCNNs) is proposed for the SPT computation. It is rigorously proved
      that the proposed model is capable of solving some optimization problems, such as
      the SPT. A static algorithm is proposed based on the M-PCNNs to compute the SPT
      efficiently for large-scale problems. In addition, a dynamic algorithm that makes
      use of the structure of the previously computed SPT is proposed, which
      significantly improves the efficiency of the algorithm. Simulation results
      demonstrate the effective and efficient performance of the proposed approach.

PMID- 23144040
TI  - Class of multiple sequence alignment algorithm affects genomic analysis.
AB  - Multiple sequence alignment (MSA) is the heart of comparative sequence analysis.
      Recent studies demonstrate that MSA algorithms can produce different outcomes
      when analyzing genomes, including phylogenetic tree inference and the detection
      of adaptive evolution. These studies also suggest that the difference between MSA
      algorithms is of a similar order to the uncertainty within an algorithm and
      suggest integrating across this uncertainty. In this study, we examine further
      the problem of disagreements between MSA algorithms and how they affect
      downstream analyses. We also investigate whether integrating across alignment
      uncertainty affects downstream analyses. We address these questions by analyzing
      200 chordate gene families, with properties reflecting those used in large-scale
      genomic analyses. We find that newly developed distance metrics reveal two
      significantly different classes of MSA methods (MSAMs). The similarity-based
      class includes progressive aligners and consistency aligners, representing many
      methodological innovations for sequence alignment, whereas the evolution-based
      class includes phylogenetically aware alignment and statistical alignment. We
      proceed to show that the class of an MSAM has a substantial impact on downstream
      analyses. For phylogenetic inference, tree estimates and their branch lengths
      appear highly dependent on the class of aligner used. The number of families, and
      the sites within those families, inferred to have undergone adaptive evolution
      depend on the class of aligner used. Similarity-based aligners tend to identify
      more adaptive evolution. We also develop and test methods for incorporating MSA
      uncertainty when detecting adaptive evolution but find that although accounting
      for MSA uncertainty does affect downstream analyses, it appears less important
      than the class of aligner chosen. Our results demonstrate the critical role that
      MSA methodology has on downstream analysis, highlighting that the class of
      aligner chosen in an analysis has a demonstrable effect on its outcome.

PMID- 23144041
TI  - Iris-based medical analysis by geometric deformation features.
AB  - Iris analysis studies the relationship between human health and changes in the
      anatomy of the iris. Apart from the fact that iris recognition focuses on
      modeling the overall structure of the iris, iris diagnosis emphasizes the
      detecting and analyzing of local variations in the characteristics of irises.
      This paper focuses on studying the geometrical structure changes in irises that
      are caused by gastrointestinal diseases, and on measuring the observable
      deformations in the geometrical structures of irises that are related to
      roundness, diameter and other geometric forms of the pupil and the collarette.
      Pupil and collarette based features are defined and extracted. A series of
      experiments are implemented on our experimental pathological iris database,
      including manual clustering of both normal and pathological iris images, manual
      classification by non-specialists, manual classification by individuals with a
      medical background, classification ability verification for the proposed
      features, and disease recognition by applying the proposed features. The results
      prove the effectiveness and clinical diagnostic significance of the proposed
      features and a reliable recognition performance for automatic disease diagnosis.
      Our research results offer a novel systematic perspective for iridology studies
      and promote the progress of both theoretical and practical work in iris
      diagnosis. 

PMID- 23144042
TI  - Estimation and prediction of drug therapy on the termination of atrial
      fibrillation by autoregressive model with exogenous inputs.
AB  - Atrial fibrillation (AF) is the most frequent cardiac arrhythmia seen in clinical
      practice. Several therapeutical approaches have been developed to terminate the
      AF and the effects are evaluated by the reduction of the wavelet number after the
      treatments. Most of the previous studies focus on modeling and analysis the
      mechanism, and the characteristic of AF. But no one discusses about the
      prediction of the result after the drug treatment. This paper is the first study
      to predict whether the drug treatment for AF is active or not. In this paper, the
      linear autoregressive model with exogenous inputs (ARX) that models the system
      output-input relationship by solving linear regression equations with least
      squares method was developed and applied to estimate the effects of
      pharmacological therapy on AF. Recordings (224-site bipolar recordings) of plaque
      electrode arrays placed on the right and left atria of pigs with sustained AF
      induced by rapid atrial-pacing were used to train and test the ARX models. The
      cardiac mapping data from twelve pigs treated with intravenous administration of
      antiarrhythmia drug, propafenone (PPF) or dl-sotalol (STL), was evaluated. The
      recordings of cardiac activity before the drug treatment were input to the model
      and the model output reported the estimated wavelet number of atria after the
      drug treatment. The results show that the predicting accuracy rate corresponding
      to the PPF and STL treatment was 100% and 92%, respectively. It is expected that
      the developed ARX model can be further extended to assist the clinical staffs to
      choose the effective treatments for the AF patients in the future. 

PMID- 23144044
TI  - Association of all-trans retinoic acid treatment with the renin-angiotensin
      aldosterone system expression in glomerulosclerosis rats.
AB  - BACKGROUND AND OBJECTIVE: All-trans retinoic acid (ATRA), a promising therapeutic
      agent, has been confirmed in animal experiments as playing a protective role
      against renal diseases. The renin-angiotensin aldosterone system (RAAS) plays a
      key role in the pathogenesis of renal diseases, and RAAS inhibitors can prevent
      the progression of kidney diseases. In our previous study, we found that ATRA
      could play a protective role against glomerulosclerosis (GS) lesions in rats, and
      its effect was similar to RAAS inhibitors. However, whether ATRA treatment was
      associated with RAAS expression was not clear. METHODS: Six-week-old male Wistar
      rats were divided into three groups: sham operation group (SHO),
      glomerulosclerosis model group without treatment (GS) and GS model group treated
      with ATRA (GA). At the end of 13 weeks, the relevant samples were collected and
      analyzed. RESULTS: The mRNA and protein expression of angiotensin-converting
      enzyme 1 (ACE1) in the GS group was notably higher when compared with the SHO
      group. However, mRNA and protein expression of ACE1 in the ATRA treatment group
      was markedly down-regulated when compared with the GS group. Angiotensin
      converting enzyme 2 (ACE2) expression (mRNA or protein) in the GS group was
      reduced compared with that in the SHO group, and ATRA markedly increased the mRNA
      and protein expression of ACE2 compared with the GS group. The levels of protein
      expression of angiotensin I and angiotensin II were significantly up-regulated in
      the GS group compared with those in the SHO group, and ATRA reduced their
      expression in the GA group when compared with the GS group. CONCLUSION: ATRA is
      associated with RAAS expression in GS rats, but its detailed mechanism needs to
      be elucidated by further research.

PMID- 23144045
TI  - Variability in cadence during forced cycling predicts motor improvement in
      individuals with Parkinson's disease.
AB  - Variability in severity and progression of Parkinson's disease symptoms makes it
      challenging to design therapy interventions that provide maximal benefit.
      Previous studies showed that forced cycling, at greater pedaling rates, results
      in greater improvements in motor function than voluntary cycling. The precise
      mechanism for differences in function following exercise is unknown. We examined
      the complexity of biomechanical and physiological features of forced and
      voluntary cycling and correlated these features to improvements in motor function
      as measured by the Unified Parkinson's Disease Rating Scale (UPDRS). Heart rate,
      cadence, and power were analyzed using entropy signal processing techniques.
      Pattern variability in heart rate and power were greater in the voluntary group
      when compared to forced group. In contrast, variability in cadence was higher
      during forced cycling. UPDRS Motor III scores predicted from the pattern
      variability data were highly correlated to measured scores in the forced group.
      This study shows how time series analysis methods of biomechanical and
      physiological parameters of exercise can be used to predict improvements in motor
      function. This knowledge will be important in the development of optimal exercise
      based rehabilitation programs for Parkinson's disease.

PMID- 23144046
TI  - The relationship between glycaemic variability and cardiovascular complications
      in patients with acute myocardial infarction and type 2 diabetes: a report from
      the DIGAMI 2 trial.
AB  - AIMS: Hyperglycaemia during hospitalization for acute myocardial infarction (AMI)
      is a risk predictor, but attempts to improve the prognosis by insulin-based
      glucose control have not been consistently successful. Increased glycaemic
      variability, a potential effect of insulin treatment, has been linked to a worse
      prognosis in critically ill patients. The present aim was to study the
      possibility of such a relation in patients with type 2 diabetes (T2DM) and AMI.
      METHOD AND RESULTS: We studied 578 T2DM patients who had glucose levels measured
      hourly while receiving an insulin-glucose infusion during the first 48 h of
      hospitalization for AMI. Three measures of glycaemic variability: root mean
      square error (RMSE), range, and slope were studied in relation to a composite
      endpoint of mortality, stroke, and reinfarction and to mortality. In unadjusted
      analyses, the mean level of glycaemic variability did not differ between patients
      who died during 12 months of follow-up compared with those who survived. In a Cox
      regression model adjusting for age and previous congestive heart failure, there
      was no increased risk for the composite endpoint associated with increased
      glycaemic variability; RMSE: hazard ratio (HR) 1.09 [95% confidence interval (CI)
      0.93-1.27; P = 0.28], range: HR 1.01 (95% CI: 0.98-1.05; P = 0.47), and slope: HR
      1.01 (95% CI: 0.99-1.04; P = 0.40). There was furthermore no increased risk in
      mortality; RMSE HR 1.14 (95% CI: 0.93-1.38; P = 0.21), range HR 1.03 (95% CI:
      0.98-1.08; P = 0.28), and slope HR 1.01 (95% CI: 0.98-1.04; P = 0.55).
      CONCLUSION: The 1-year risk for death, reinfarction, or stroke did not relate to
      glycaemic variability in T2DM patients with AMI treated with insulin infusion.

PMID- 23144047
TI  - Prognostic role of persistent positive blood cultures after initiation of
      antibiotic therapy in left-sided infective endocarditis.
AB  - AIM: Persistent infection is not a scientific evidence-based definition. The
      guidelines of infective endocarditis (IE) establish a cut-off point of 7-10 days,
      which is arbitrary and probably too long. Our hypothesis is that persistent
      positive blood cultures after 48-72 h from the initiation of antibiotic therapy
      are associated with a worse prognosis in patients with left-sided IE. METHODS AND
      RESULTS: We repeated blood cultures after 48-72 h of the initiation of the
      antibiotic treatment in 407 patients with left-sided IE of a total of 692
      episodes consecutively diagnosed from 1996 to 2011. We have compared the profile
      of patients whose blood cultures became negative and those with persistent
      positive blood cultures. We performed a multivariate logistic regression model to
      determine the prognostic implication of persistent positive blood cultures. Of
      256 patients with positive blood cultures at admission, 89 (35%) had persistent
      positive cultures after 48-72 h from the initiation of the antibiotic treatment.
      Persistent positive blood cultures (OR: 2.1; 95% CI: 1.2-3.6), age (OR: 1.026;
      95% CI: 1.007-1.046), Staphylococcus aureus infection (OR: 3.3; 95% CI: 1.6-6.6),
      heart failure (OR: 2.8; 95% CI: 1.6-4.7), and renal failure (OR: 2.9; 95% CI: 1.8
      4.9) were found to be independently associated with higher in-hospital mortality.
      CONCLUSIONS: The presence of persistent positive blood cultures is an independent
      risk factor for in-hospital mortality which doubles the risk of death of patients
      with left-sided IE. It should be taken into account in the risk stratification of
      these patients.

PMID- 23144048
TI  - Resistant hypertension: a frequent and ominous finding among hypertensive
      patients with atherothrombosis.
AB  - AIMS: The effect of resistant hypertension on outcomes in patients with
      atherothrombotic disease is currently unknown. Accordingly, we sought to
      determine the prevalence and outcomes of resistant hypertension in stable
      hypertensive outpatients with subclinical or established atherothombotic disease
      enrolled in the international Reduction of Atherothrombosis for Continued Health
      (REACH) registry. METHODS AND RESULTS: Resistant hypertension was defined as a
      blood pressure >=140/90 mmHg at baseline (>=130/80 mmHg if diabetes/renal
      insufficiency) with the use of >=3 antihypertensive medications, including a
      diuretic. The primary outcome was a composite of cardiovascular death, myocardial
      infarction, or stroke at 4 years. A total of 53 530 hypertensive patients were
      included. The prevalence of resistant hypertension was 12.7%; 6.2% on 3
      antihypertensive agents, 4.6% on 4 agents, and 1.9% on >=5 agents (mean: 4.7 +/-
      0.8). In addition to a diuretic, these patients were being treated mostly with
      ACE-inhibitors/angiotensin receptor blockers (90.1%), beta-blockers (67.0%), and
      calcium channel blockers (50.8%). Patients with resistant hypertension had a
      higher risk of the primary endpoint on multivariable analysis [hazard ratio (HR)
      1.11, 95% confidence interval (CI) 1.02-1.20; P = 0.017], including an increased
      non-fatal stroke risk (HR: 1.26; 95% CI: 1.10-1.45; P = 0.0008). Hospitalizations
      due to congestive heart failure were higher (P < 0.0001). Patients on >=5 agents
      had a higher adjusted risk for the primary endpoint when compared with those on
      <=3 agents (P = 0.03). CONCLUSION: The presence of resistant hypertension
      identifies a subgroup of patients with hypertension and atherothrombosis who are
      at heightened risk for adverse long-term outcomes.

PMID- 23144050
TI  - Virus-induced appearance of the selectin ligand sLeX in herpes simplex virus type
      1-infected T-cells: involvement of host and viral factors.
AB  - Circulating leukocytes that express selectin ligands such as the carbohydrate
      epitope sialyl Lewis X (sLeX) may interact with endothelial selectins, resulting
      in transmigration of the leukocyte across the endothelial wall to adjacent
      tissue. Due to the potential of selectin-ligand interactions as targets in viral
      pathogenesis, we aimed at determining whether herpes simplex virus type 1 (HSV1)
      is able to induce the appearance of sLeX at the surface of infected leukocytes.
      We found that HSV1 infection of a T-cell line resulted in transcriptional
      activation of human fucosyltransferase genes FUT3, FUT6 and FUT7, the two latter
      genes encoding the fucosyltransferases rate limiting for sLeX synthesis. Flow
      cytometry and confocal microscopy demonstrated that HSV1 infection resulted in a
      2-fold rise in the proportion of sLeX-positive cells. Increased levels of FUT3,
      FUT6 and FUT7 RNA were detected already at 3 h post infection, and treatment with
      cycloheximide, a translation inhibitor, blocked a HSV1-induced increase in the
      expression of FUT3, FUT6 and FUT7 RNA, suggesting involvement of viral or
      cellular proteins. Studies with infectious viral mutants indicated that the viral
      immediate early (alpha) protein ICP0 is essential for the initiation of FUT7
      though not for FUT3 or FUT6 transcription. In CD3+ cells, derived from peripheral
      blood mononuclear cells, HSV1 infection induced expression of FUT3, FUT5 and
      FUT6, whereas FUT7 was not altered. The mean sLeX fluorescence intensity of CD3+
      cells was significantly higher in HSV1-infected CD3+ cells. This suggests that
      infected leukocytes during HSV1 viremia may express selectin ligands with
      possible but as yet unproven roles in viral pathogenesis.

PMID- 23144051
TI  - The prenatal care at school program.
AB  - School absenteeism and poor compliance with prenatal appointments are concerns
      for pregnant teens. The Prenatal Care at School (PAS) program is a new model of
      prenatal care involving local health care providers and school personnel to
      reduce the need for students to leave school for prenatal care. The program
      combines prenatal care and education designed specifically for adolescents.
      Twenty-eight girls attended PAS in the fall of 2010. Program evaluation results
      showed a 14.2% increase in school attendance among students enrolled compared to
      peers enrolled the previous year, a 5.7% increase over a local teen clinic's
      attendance to their group prenatal care program, and a 42% increase in pregnancy
      and childbirth knowledge. Satisfaction surveys indicated that participants all
      believed that PAS helped prepare them for labor and delivery and 92% felt
      encouraged to stay in school. This pilot program benefited pregnant teens by
      increasing school educational time, improving preparation for labor and delivery,
      and increasing participation with prenatal care.

PMID- 23144052
TI  - Inconsistent placebo effects in NICE's network analysis.

PMID- 23144053
TI  - High urinary ACE2 concentrations are associated with severity of glucose
      intolerance and microalbuminuria.
AB  - OBJECTIVE: Angiotensin-converting enzyme 2 (ACE2) plays an important role in
      glucose metabolism and renal function. However, the relationship between ACE2 and
      hyperglycemia or microalbuminuria has not been established in humans. We
      investigated whether urinary ACE2 levels are associated with abnormal glucose
      homeostasis and urinary albumin excretion. METHODS: We developed an ELISA for
      quantifying ACE2 in urine. The ELISA was used to measure urinary ACE2 levels in
      621 subjects with: normal glucose tolerance (NGT; n=77); impaired fasting glucose
      (IFG) or impaired glucose tolerance (IGT) (n=132); and type 2 diabetes mellitus
      (T2DM, n=412). Insulin resistance was assessed by homeostasis model assessment
      for insulin resistance (HOMA-IR) index and urinary albumin excretion by urine
      albumin-to-creatinine ratio (ACR). Other biochemical and anthropometric
      parameters were measured. RESULTS: Urinary ACE2 levels were significantly higher
      in insulin-resistant subjects with IFG, IGT, and T2DM than in the NGT group
      (P<0.001). Urinary ACE2 concentrations appeared to correlate with HOMA-IR,
      fasting blood glucose, triglyceride, high-sensitivity C-reactive protein, serum
      creatinine, urinary ACR, and systolic blood pressure (all P<0.05). After
      adjustment for impaired renal function and other metabolic parameters, urinary
      ACE2 concentration was still associated with a higher risk for T2DM (OR 1.80, 95%
      CI 1.05-3.08, P=0.02). In addition, urinary ACE2 levels were highly predictive of
      microalbuminuria after adjusting for clinical risk factors (OR 2.68, 95% CI 1.55
      4.64, P<0.001). CONCLUSION: Our data suggest that the urinary ACE2 level is
      closely associated with T2DM and is an independent risk factor for
      microalbuminuria.

PMID- 23144054
TI  - Bone marrow-mesenchymal stem cells are a major source of interleukin-7 and
      sustain colitis by forming the niche for colitogenic CD4 memory T cells.
AB  - OBJECTIVE: Interleukin (IL)-7 is mainly produced in bone marrow (BM) that forms
      the niche for B cells. We previously demonstrated that BM also retains pathogenic
      memory CD4 T cells in murine models of inflammatory bowel disease (IBD). However,
      it remains unknown whether BM-derived IL-7 is sufficient for the development of
      IBD and which cells form the niche for colitogenic memory CD4 T cells in BM.
      DESIGN: To address these questions, we developed mice in which IL-7 expression
      was specific for BM, and identified colitis-associated IL-7-expressing
      mesenchymal stem cells (MSC) in the BM. RESULTS: IL-7-/-*RAG-1-/- mice injected
      with BM cells from IL-7+/+*RAG-1-/- mice, but not from IL-7-/-*RAG-1-/- mice,
      expressed IL-7 in BM, but not in their colon, and developed colitis when injected
      with CD4+CD45RBhigh T cells. Cultured BM MSC stably expressed a higher level of
      IL-7 than that of primary BM cells. IL-7-sufficient, but not IL-7-deficient, BM
      MSC supported upregulation of Bcl-2 in, and homeostatic proliferation of,
      colitogenic memory CD4 T cells in vitro. Notably, IL-7-/-*RAG-1-/- mice
      transplanted with IL-7-sufficient, but not IL-7-deficient, BM MSC expressed IL-7
      in BM, but not in their colon, and developed colitis when transplanted with
      CD4+CD45RBhigh T cells. CONCLUSIONS: We demonstrate for the first time that BM
      MSC are a major source of IL-7 and play a pathological role in IBD by forming the
      niche for colitogenic CD4 memory T cells in BM.

PMID- 23144055
TI  - Liver disease progression and virological response: entecavir rescue still
      possible in the setting of rtM204I lamivudine-resistant mutation.

PMID- 23144061
TI  - Specific learning disability and its newest definition: which is comprehensive?
      And which is insufficient?
AB  - The American Psychiatric Association's proposed definition of specific learning
      disability ("specific learning disorder") for the DSM-5 reflects current thinking
      and best practice in learning disabilities. It continues the core
      conceptualization of learning disability (LD) as well as proposes identification
      criteria to supplant the discredited aptitude-achievement discrepancy formula.
      Improvements can be found along with long-standing and new controversies about
      the nature of LD. The proposed definition both provides a model of a currently
      acceptable definition and reflects critical issues in the operationalization of
      LD that the field continues to neglect.

PMID- 23144056
TI  - Whither the attenuated psychosis syndrome?

PMID- 23144062
TI  - Rethinking ADHD and LD in DSM-5: proposed changes in diagnostic criteria.
AB  - The Diagnostic and Statistical Manual of Mental Disorders (DSM) is currently
      undergoing revision that will lead to a fifth edition (DSM-5) in 2013. This
      article first provides a brief synopsis of the DSM-5 administrative structure,
      procedures, and guiding principles to enhance understanding of how changes are
      made in the DSM. The next two sections (on attention-deficit/hyperactivity
      disorder and learning disorders, respectively) highlight the major concerns and
      controversies surrounding the DSM-IV diagnostic criteria for these two disorders
      and provide a rationale for the proposed changes to the criteria, along with a
      commentary on the empirical evidence on which the proposed changes were based.

PMID- 23144063
TI  - Comorbidity of LD and ADHD: implications of DSM-5 for assessment and treatment.
AB  - Attention-deficit/hyperactivity disorder (ADHD) and learning disability (LD) can
      co-occur for a significant minority of children with each disorder. A total of 17
      studies (2001-2011) examining ADHD-LD comorbidity were reviewed, revealing a
      higher mean comorbidity rate (45.1%) than has been obtained previously. Higher
      comorbidity may be the result of including students with writing disorders, not
      just reading and/or math disabilities. Proposed DSM-5 criteria for both disorders
      will likely affect comorbidity rates; however, it is unclear whether such rates
      will increase or decrease. Regardless of the specific impact of DSM revisions,
      academic skill and/or performance deficits should be assessed for students with
      ADHD as part of screening, comprehensive evaluation, and treatment monitoring.
      Comprehensive intervention services for students with comorbid ADHD and LD will
      require empirically supported treatment strategies that address both disorders
      and that are implemented across school and home settings.

PMID- 23144064
TI  - Culprit lesion remodelling and long-term prognosis in patients with acute
      coronary syndrome: an intravascular ultrasound study.
AB  - AIMS: Positive arterial remodelling is recognized as one of the morphological
      characteristics of the vulnerable plaque. Limited data are available on a long
      term outcome of acute coronary syndrome (ACS) patients with culprit lesion
      positive arterial remodelling (PR). The aim of this study was to investigate the
      long-term impact of culprit lesion PR in patients with ACS. METHODS AND RESULTS:
      In 134 patients with ACS, intravascular ultrasound (IVUS) was performed to assess
      target lesion remodelling before percutaneous coronary intervention. PR was
      defined as the ratio of the external elastic membrane cross-sectional area at the
      target lesion to that of at the proximal reference of >1.05, and intermediate or
      negative remodelling (IR/NR) was defined as that of <=1.05. Major adverse cardiac
      event (MACE) was defined as a composite of death, ACS, and target lesion
      revascularization. During the follow-up (median 5.8 years), MACE-free survival
      was significantly lower in the PR group than that in the IR/NR group (log-rank, P
      = 0.005). Survival and ACS-free survival were also significantly lower in the PR
      group than that in the IR/NR group (log-rank, both P = 0.04). By multivariable
      Cox regression analysis, PR (hazard ratio = 2.4, P = 0.02) and diabetes (hazard
      ratio = 1.9, P = 0.03) were independent predictors of MACE. CONCLUSION: Culprit
      lesion PR was associated with a poor long-term prognosis in patients with ACS. PR
      may be a marker of vulnerable patients.

PMID- 23144065
TI  - Giant aortic pseudoaneurysm presented with acute coronary syndrome by compressing
      the coronary arterial system.

PMID- 23144066
TI  - The enigma of decreased creatinine generation in acute kidney injury.

PMID- 23144067
TI  - Dialysis Duration: The longer the better, but why? [corrected].

PMID- 23144068
TI  - Nephrolithiasis and urinary tract infections: 'the chicken or the egg' dilemma?

PMID- 23144069
TI  - Parvalbumin: calcium and magnesium buffering in the distal nephron.
AB  - Parvalbumin (PV) is a classical member of the EF-hand protein superfamily that
      has been described as a Ca(2+) buffer and Ca(2+) transporter/shuttle protein and
      may also play an additional role in Mg(2+) handling. PV is exclusively expressed
      in the early part of the distal convoluted tubule in the human and mouse kidneys.
      Recent studies in Pvalb knockout mice revealed a role of PV in the distal
      handling of electrolytes: the lack of PV was associated with a mild salt-losing
      phenotype with secondary aldosteronism, salt craving and stronger bones compared
      with controls. A link between the Ca(2+)-buffering capacity of PV and the
      expression of the thiazide-sensitive Na(+)-Cl(-) cotransporter was established,
      which could be relevant to the regulation of sodium transport in the distal
      nephron. Variants in the PVALB gene that encodes PV have been described, but
      their relevance to kidney function has not been established. PV is also
      considered a reliable marker of chromophobe carcinoma and oncocytoma, two
      neoplasms deriving from the distal nephron. The putative role of PV in tumour
      genesis remains to be investigated.

PMID- 23144070
TI  - Systems biology: building a useful model from multiple markers and profiles.
AB  - The pathophysiology of diabetic nephropathy (DN) is driven by a complex, multi
      facetted interplay of numerous molecular processes (protective as well as
      damaging) and the balance between these, rather than the activity of a single
      pathway, determines clinical presentation and outcome. We present a concept for
      deriving a biomarker panel aimed to represent the relevant processes involved.
      Our approach rests on a hybrid gene/protein interaction network that holds ample
      information on molecular features (nodes) and their relations (edges), as a
      result providing a basic structure to navigate in molecular content and context
      being identified as relevant in DN. Extensive literature search on omics studies
      in DN provided a molecular feature list mapping to a total of 2175 unique protein
      coding genes [13 from single nucleotide polymorphisms (SNPs), 12 as targets from
      relevant miRNAs, 1583 from transcriptomics, 5 from proteomics and 53 from
      metabolomics via linking to enzymes; 509 features were identified from multiple
      sources]. Two hundred and eighty-seven further human protein-coding genes
      associated with DN were derived from searching NCBI Pubmed (utilizing MeSH and
      gene-to-pubmed). Text mining of patents and clinical trial descriptors in the
      context of DN further added about 1,000 features. These data were used to label
      the respective nodes in the interaction network, as a result obtaining a DN
      specific subgraph. Application of a segmentation algorithm on this subgraph
      allowed the identification of DN-specific molecular units, each characterizing a
      cluster of genes/proteins with a high internal functional association. We
      interpret each such unit as a functionally relevant molecular process
      contributing to the presentation of DN, and the total set of such units as a
      molecular model of DN. We propose that selecting appropriate biomarkers from each
      unit might allow the description of a patient's specific 'type' of DN, ultimately
      leading to a better stratification of patients regarding progression risk and
      optimal interventional approach.

PMID- 23144071
TI  - Screening for chronic kidney disease can be of help to prevent atherosclerotic
      end-organ damage.
AB  - Atherosclerotic damage to the kidney is one of the most prevalent causes of
      chronic kidney disease and ultimately kidney failure. It frequently coincides
      with atherosclerotic damage to the heart, the brain and the lower extremities. In
      fact, the severity of the damage in the various end organs runs in parallel. As
      damage to the kidney is easy to measure by monitoring albuminuria and eGFR, and
      as the early phases of kidney damage frequently precede the alarming
      symptomatology in the heart, brain and peripheral vasculature, we argue that the
      nephrologist should consider taking the lead in better organizing early detection
      and management of CKD. The nephrologist can guide the general practitioner and
      general health care workers to offer better preventive care to the subjects at
      risk of progressive atherosclerotic end-organ damage.

PMID- 23144072
TI  - Economic evaluation of different treatment modalities in acute kidney injury.
AB  - BACKGROUND: Major controversy exists regarding the preferred treatment option for
      acute kidney injury (AKI). The purpose of this study was to assess the
      incremental cost-effectiveness of continuous renal replacement therapy (CRRT)
      versus intermittent renal replacement therapy (IRRT) and conservative (CONS) AKI
      treatment in Belgium. METHODS: An area-under-the-curve model based on survival
      analysis was used to estimate costs and health outcomes using a 2-year time
      horizon. Input data were derived from the multi-centre Stuivenberg Hospital Acute
      Renal Failure 4 study. RESULTS: Analyses indicated that in-hospital mortality,
      hospitalization costs and hospital length of stay differed significantly between
      treatment modes. Follow-up mortality rates and follow-up cost per day showed no
      significant difference between the treatment modes. Utility values, which
      improved gradually after admission to the hospital, revealed no significant
      differences between the three treatment strategies. CONS treatment was associated
      with a 2-year cost of 33,802? and 0.54 quality-adjusted life years (QALYs). The
      CRRT was the most expensive therapy with a cost of 51,365? leading to 0.57 QALYs.
      The cost and QALYs associated with IRRT were 43,445? and 0.50, respectively. One
      way sensitivity analyses indicated the 'in-hospital mortality' as the variable
      with the greatest influence on the results. Probabilistic sensitivity analysis
      resulted in a significant difference in treatment costs but no significant
      difference in QALY gain. CONCLUSIONS: This study has indicated that the most
      expensive treatment (CRRT) associated with an incremental cost of approximately
      ?7920 generates only a minor non-significant increase in QALYs of 0.07 compared
      with IRRT. Additionally, the results revealed that the RRTs did not result in a
      significant increase in QALYs despite their higher cost compared with the CONS
      treatment. From a health economic perspective, the latter seems to be the
      preferred treatment strategy.

PMID- 23144073
TI  - Serum level of fibroblast growth factor 23 in maintenance renal transplant
      patients.
AB  - BACKGROUND: The discovery of fibroblast growth factor 23 (FGF23) provides a new
      conceptual framework that improves our understanding of the pathogenesis of post
      transplant bone disease. Excess FGF23 is produced in the early post-transplant
      period; levels return to normal in the months following transplant. However, few
      manuscripts discuss FGF23 levels in stable long-term renal transplant recipients.
      METHODS: We performed a cross-sectional observational study of 279 maintenance
      kidney recipients with chronic kidney disease (CKD) Stages 1-4 and stable
      allograft function who had received their transplant at least 12 months
      previously. We calculated the estimated GFR (eGFR) using the MDRD4 equation.
      RESULTS: FGF23, parathyroid hormone (PTH) and phosphorus values were higher in
      more advanced stages, while the serum calcitriol levels and the phosphate
      reabsorption rate were lower. A significant inverse correlation was found between
      eGFR and FGF23 (r = -0.487; P < 0.001), PTH (r = -0.444; P < 0.001), serum
      phosphate levels (r = -0.315; P < 0.001) and fractional excretion of magnesium (r
      = -0.503; P < 0.001). Multivariable analysis showed that increased time on
      corticosteroids (P < 0.001), PTH (P < 0.001), serum phosphate (P = 0.003),
      decreased serum calcitriol (P = 0.049) and estimated glomerular filtration (P =
      0.003) rate were associated with high FGF23 levels. In contrast with pre
      transplant patients and first year post-transplant patients, higher FGF23 values
      were not correlated with increased phosphate excretion. An elevated phosphate
      reabsorption rate was associated with decreased PTH (P < 0.001) and calciuria (P
      = 0.028) and increased serum calcitriol (P = 0.009), plasma bicarbonate (P =
      0.024) and estimated glomerular filtration (P = 0.003). CONCLUSIONS: Serum FGF23
      concentrations remain increased in long-term kidney graft recipients, even in the
      early stages of CKD. It remains to be seen whether measures aimed at reducing
      serum levels of PTH and phosphate and/or corticosteroid doses might help to lower
      serum FGF23 and whether this will improve kidney recipient outcomes.

PMID- 23144074
TI  - COL4A5-associated X-linked Alport syndrome in a female patient with early inner
      ear deafness due to a mutation in MYH9.
AB  - Alport syndrome (ATS) is a type-IV collagen inherited disorder, caused by
      mutations in COL4A3 and COL4A4 (autosomal recessive) or COL4A5 (X-linked).
      Clinical symptoms include progressive renal disease, eye abnormalities and high
      tone sensorineural deafness. A renal histology very similar to ATS is observed in
      a subset of patients affected by mutations in MYH9, encoding non-muscle-myosin
      Type IIa--a cytoskeletal contractile protein. MYH9-associated disorders (May
      Hegglin anomaly, Epstein and Fechtner syndrome, and others) are inherited in an
      autosomal dominant manner and characterized by defects in different organs
      (including eyes, ears, kidneys and thrombocytes). We describe here a 6-year-old
      girl with haematuria, proteinuria, and early sensorineural hearing loss. The
      father of the patient is affected by ATS, the mother by isolated inner ear
      deafness. Genetic testing revealed a pathogenic mutation in COL4A5 (c.2605G>A) in
      the girl and her father and a heterozygous mutation in MYH9 (c.4952T>G) in the
      girl and her mother. The paternal COL4A5 mutation seems to account for the
      complete phenotype of ATS in the father and the maternal mutation in MYH9 for the
      inner ear deafness in the mother. It has been discussed that the interaction of
      both mutations could be responsible for both the unexpected severity of ATS
      symptoms and the very early onset of inner ear deafness in the girl.

PMID- 23144075
TI  - Editor's snapshot: an unexpected duodenal finding.

PMID- 23144076
TI  - The enteric serotonergic system is altered in patients with diverticular disease.
AB  - OBJECTIVE: Disturbances of the enteric serotonergic system have been implicated
      in several intestinal motility disorders. Patients with diverticular disease (DD)
      have been reported to exhibit abnormal intestinal motility and innervation
      patterns. Gene expression profiles of the serotonergic system and distribution of
      the serotonin type 4 receptor (5HT-4R) were thus studied in patients with DD.
      DESIGN: Colonic specimens from patients with DD and controls were subjected to
      quantitative PCR for serotonin receptors 2B, 3A, 4, serotonin transporter and
      synthesising enzyme tryptophan hydroxylase. Localisation of 5HT-4R was determined
      by dual-label immunocytochemistry using smooth muscle actin (alpha-SMA) and pan
      neuronal markers (PGP 9.5) and quantitative analysis was carried out. Site
      specific gene expression analysis of 5HT-4R was assessed within myenteric ganglia
      and muscle layers. Correlation of 5HT-4R with muscarinic receptors 2 and 3 (M2R,
      M3R) messenger RNA expression was determined. RESULTS: 5HT-4R mRNA expression was
      downregulated in the tunica muscularis and upregulated in the mucosa of patients
      with DD, whereas the other components of the serotonergic system remained
      unchanged. 5HT-4R was detected in ganglia and muscle layers, but was decreased in
      the circular muscle layer and myenteric ganglia of patients with DD. 5HT-4R mRNA
      expression correlated with M2R/M3R mRNA expression in controls, but not in
      patients with DD. CONCLUSIONS: The serotonergic system is compromised in DD.
      Altered expression of 5HT-4R at mRNA and protein levels may contribute to
      intestinal motor disturbances reported in patients with DD. The findings support
      the hypothesis that DD is associated and possibly promoted by an enteric
      neuromuscular pathology.

PMID- 23144077
TI  - Psychosocial care for persons affected by emergencies and major incidents: a
      Delphi study to determine the needs of professional first responders for
      education, training and support.
AB  - BACKGROUND: The role of ambulance clinicians in providing psychosocial care in
      major incidents and emergencies is recognised in recent Department of Health
      guidance. The study described in this paper identified NHS professional first
      responders' needs for education about survivors' psychosocial responses, training
      in psychosocial skills, and continuing support. METHOD: Ambulance staff
      participated in an online Delphi questionnaire, comprising 74 items (Round 1) on
      7-point Likert scales. Second-round and third-round participants each received
      feedback based on the previous round, and responded to modified versions of the
      original items and to new items for clarification. RESULTS: One hundred and two
      participants took part in Round 1; 47 statements (64%) achieved consensus. In
      Round 2, 72 people from Round 1 participated; 15 out of 39 statements (38%)
      achieved consensus. In Round 3, 49 people from Round 2 participated; 15 out of 27
      statements (59%) achieved consensus. Overall, there was consensus in the
      following areas: 'psychosocial needs of patients' (consensus in 34/37 items);
      'possible sources of stress in your work' (8/9); 'impacts of distress in your
      work' (7/10); 'meeting your own emotional needs' (4/5); 'support within your
      organisation' (2/5); 'needs for training in psychosocial skills for patients'
      (15/15); 'my needs for psychosocial training and support' (5/6). CONCLUSIONS:
      Ambulance clinicians recognise their own education needs and the importance of
      their being offered psychosocial training and support. The authors recommend
      that, in order to meet patients' psychosocial needs effectively, ambulance
      clinicians are provided with education and training in a number of skills and
      their own psychosocial support should be enhanced.

PMID- 23144079
TI  - A review of blood component usage in a large UK emergency department after
      implementation of simple measures.
AB  - OBJECTIVES: To review clinical indications and demographics of transfusion and
      the patterns of blood component ordering, transfusion, wastage and traceability,
      before (2007) and after (2011) implementation of simple improvement strategies.
      METHODS: Retrospective case note review of all patients presenting to the Royal
      Infirmary of Edinburgh (RIE) Emergency Department (ED) for whom a blood component
      was requested and historic comparison. Improvement measures implemented between
      2007 and 2011 included (1) formal staff education, (2) use of e-learning Module
      One Safe Transfusion Practice (traceability update, Medicines and Healthcare
      products Regulatory Agency (MHRA) traceability regulations and importance of
      returning completed blood component tags), (3) an ED resuscitation room blood
      fridge, (4) introduction of a dedicated ED transfusion consultant and ED
      transfusion link nurse and (5) the presence of an ED consultant on the Hospital
      Transfusion Group. RESULTS: Between 1st January and 31st December 2011, blood
      components were requested for 255 patient episodes, totalling 1034 individual
      units. 687 units (66.4%) of blood component were transfused, 248 components
      (24.0%) were recycled, 90 components (8.7%) were discarded and nine units (0.9%)
      were unaccounted for. There was a 64% reduction in blood component ordering (3209
      vs 1034 units), a 39% reduction in blood component transfusion (1131 vs 687
      units) and a 96% reduction in unaccounted units (214 vs 9 units) between 2007 and
      2011. There was a rise in the median age of the patient for whom a transfusion
      request was made from 63.9 years in 2007 to 67.0 years in 2011. CONCLUSIONS:
      Blood component ordering, usage and traceability within the ED have improved
      significantly since 2007 following implementation of simple strategies. The age
      of ED transfusion recipients is increasing.

PMID- 23144078
TI  - TRAIL conjugated to nanoparticles exhibits increased anti-tumor activities in
      glioma cells and glioma stem cells in vitro and in vivo.
AB  - Glioblastomas (GBM) are characterized by resistance to chemotherapy and
      radiotherapy, and therefore, alternative therapeutic approaches are needed. TRAIL
      induces apoptosis in cancer but not in normal cells and is considered to be a
      promising anti-tumor agent. However, its short in vivo half-life and lack of
      efficient administration modes are serious impediments to its therapeutic
      efficacy. Nanoparticles (NP) have been used as effective delivery tools for
      various anticancer drugs. TRAIL was conjugated to magnetic ferric oxide NP by
      binding the TRAIL primary amino groups to activated double bonds on the surface
      of the NP. The effect of NP-TRAIL was examined on the apoptosis of glioma cells
      and self-renewal of glioma stem cells (GSCs). In addition, the ability of the NP
      TRAIL to track U251 cell-derived glioma xenografts and to affect cell apoptosis,
      tumor volume, and survival among xenografted rats was also examined. Conjugation
      of TRAIL to NP increased its apoptotic activity against different human glioma
      cells and GSCs, as compared with free recombinant TRAIL. Combined treatment with
      NP-TRAIL and gamma-radiation or bortezomib sensitized TRAIL-resistant GSCs to NP
      TRAIL. Using rhodamine-labeled NP and U251 glioma cell-derived xenografts, we
      demonstrated that the NP-TRAIL were found in the tumor site and induced a
      significant increase in glioma cell apoptosis, a decrease in tumor volume, and
      increased animal survival. In summary, conjugation of TRAIL to NP increased its
      apoptotic activity both in vitro and in vivo. Therefore, NP-TRAIL represents a
      targeted anticancer agent with more efficient action for the treatment of GBM and
      the eradication of GSCs.

PMID- 23144080
TI  - Prehospital non-drug assisted intubation for adult trauma patients with a Glasgow
      Coma Score less than 9.
AB  - OBJECTIVES: Prehospital airway management for adult trauma patients remains
      controversial. We sought to review the frequency that paramedic non-drug assisted
      intubation or attempted intubation is performed for trauma patients in Ontario,
      Canada, and determine its association with mortality. METHODS: We conducted a
      retrospective cohort study using the Ontario Trauma Registry's Comprehensive Data
      Set for 2002-2009. Eligible patients were greater than 16 years of age, had an
      initial Glasgow Coma Score of less than 9 and were cared for by ground-based non
      critical care paramedics. The primary outcome was mortality. Outcomes were
      compared between patients undergoing prehospital intubation versus basic airway
      management. Logistic regression analyses were used to quantify the association
      between prehospital intubation and mortality. RESULTS: Of the 2229 patients
      included in the analysis, 671 (30.1%) underwent prehospital intubation. Annual
      rates of prehospital intubation declined from 33.7% to 14.0% (ptrend<0.0001) over
      the study period. Unadjusted death rates were 66.0% versus 34.8% in the
      intubation and basic airway groups, respectively (p<0.0001). Intubation in the
      prehospital setting was associated with a heightened risk of mortality (adjusted
      OR 2.8, 95% CI 1.1 to 7.6). CONCLUSIONS: Prehospital non-drug assisted intubation
      for trauma is being performed less frequently in Ontario, Canada. Within our
      study population, paramedic non-drug assisted intubation or attempted intubation
      was associated with a heightened risk of mortality.

PMID- 23144081
TI  - A novel clinical and imaging based score for predicting outcome prior to
      endovascular treatment of acute ischemic stroke.
AB  - INTRODUCTION: Outcome after stroke intervention remains disappointing, with only
      30-50% of patients having a good outcome at 90 days. We sought to identify
      important outcome prognosticators. METHODS: All consecutive patients that
      presented with an acute anterior circulation ischemic stroke, with adequate CT
      perfusion imaging, and that underwent emergency endovascular treatment at two
      centers between January 1, 2009 and November 2011, were retrospectively reviewed.
      Investigators estimated the percentage of the total ischemic tissue that had
      decreased cerebral blood volume (CBV) compared with the total area with elevated
      time to peak (the penumbra). Multivariate regression analyses were performed to
      identify variables with prognostic significance and a scoring system was created.
      RESULTS: 163 patients underwent endovascular treatment for acute ischemic stroke.
      Outcome data were available in 147 patients (90.2%). A good outcome (modified
      Rankin Scale score 0-2) occurred in 64 patients (43.5%). Age, National Institutes
      of Health Stroke Scale (NIHSS) score and per cent decreased CBV scores were the
      only variables that predicted prognosis on multivariate analyses. A score was
      created (NAV score-NIHSS, age, volume) that awards points based on these three
      factors: 2 points for an NIHSS score of >= 15, 1 point for age >= 70 years, and 1
      point for decreased CBV of >= 50%. The NAV score was strongly correlated with
      overall outcome (p<0.01): scores of 0, 1, 2, 3, and 4 were associated with 84%,
      50%, 36%, 25%, and 8% chance of a good outcome at 90 days. CONCLUSIONS: We
      introduced a simple three factor scoring system to help predict outcome in
      patients deemed candidates for intra-arterial acute ischemic stroke intervention.

PMID- 23144082
TI  - Caution during use of desmopressin in IPSS.

PMID- 23144093
TI  - Rhinitis associated with allergic nasal granuloma in Jersey cattle.

PMID- 23144083
TI  - Anxiety sensitivity as a predictor of acute subjective effects of smoking.
AB  - INTRODUCTION: Anxiety sensitivity (i.e., AS; the degree to which one believes
      that anxiety and its related sensations are harmful) is a stable trait that is
      associated with habitual smoking. Yet, the mechanisms linking AS and smoking are
      unclear. A promising hypothesis is that high-AS individuals are more sensitive to
      the acute subjective reinforcing effects of smoking and are, therefore, more
      prone to tobacco dependence. This study examined trait AS as a predictor of
      several subjective effects of cigarette smoking. METHODS: Adult non-treatment
      seeking smokers (N = 87; 10+ cigarettes/day) completed a measure of AS during a
      baseline session. Prior to a subsequent experimental session, participants were
      asked to smoke normally before their appointment. At the outset of that visit,
      each participant smoked a single cigarette of their preferred brand in the
      laboratory. Self-report measures of affect and cigarette craving were completed
      before and after smoking, and post-cigarette subjective effect ratings were
      provided. RESULTS: AS predicted greater increases in positive affect from pre- to
      post-cigarette (beta = .30, p = .006) as well as greater smoking satisfaction and
      psychological reward (beta = .23 to .48, ps < .03). Each of these effects
      remained statistically significant after adjusting for anxiety symptom severity.
      AS did not predict the degree of negative affect and craving suppression or post
      cigarette aversive effects. CONCLUSIONS: These findings suggest that positive
      reinforcement mechanisms may be particularly salient etiological processes that
      maintain smoking in high-AS individuals.

PMID- 23144094
TI  - Pulse antibiotic therapy: it's time to cut back.

PMID- 23144095
TI  - Bovine TB and badger culling.

PMID- 23144096
TI  - Reference intervals and working ferrets.

PMID- 23144098
TI  - Inactivated poliovirus vaccine, the fog of uncertainty is lifting.

PMID- 23144099
TI  - PALS update 2010.
AB  - During the past decade, guidelines for cardiopulmonary resuscitation have focused
      on the importance of high quality CPR. The purpose is to temporarily maintain a
      circulation to vital organs until specialized treatment is available. In,
      essence, it has been a revolution in pediatric resuscitation in terms of coming
      full circle to the 1960s when basic CPR was first developed. A fifth component to
      the pediatric chain of survival has been added with emphasis on integrated post
      cardiac arrest care. With mounting scientific evidences, American Heart
      Association published new Pediatric Advanced life support 2010 guidelines in
      accordance with the established five yearly cycle of guideline changes.

PMID- 23144100
TI  - Immune thrombocytopenic purpura: historical perspective, current status, recent
      advances and future directions.
AB  - Immune thrombocytopenic purpura (ITP) has witnessed many changes and updates over
      the past decade. The definitions of disease subtypes, course and response to
      treatment have all been standardized recently. Consequent to the lack of an
      international consensus management guideline, wide variations exist in treatment
      practice. This is now being addressed to an extent by the much awaited ITP
      International Working Group 2010 recommendations. The pathophysiologic mechanisms
      have been unfolded at cellular, molecular and humoral levels. As a result, many
      recent advances have taken place in the management of this disorder. This review
      revisits the history of evolution of ITP, summarizes the current recommendations
      for management and lists the recent advances and future prospects in this field.

PMID- 23144101
TI  - Ruptured sinus of Valsalva masquerading as rheumatic heart disease.
AB  - Ruptured sinus of Valsalva is a rare lesion in pediatric age group. We are
      reporting a twelve year old child with hyperdynamic circulation being diagnosed
      and treated as Rheumatic heart disease.

PMID- 23144102
TI  - Rituximab followed by mycophenolate mofetil in children with IgM nephropathy.
AB  - IgM nephropathy presents with refractory nephrotic syndrome and its treatment is
      a significant challenge for pediatricians. We present two patients with IgM
      nephropathy and frequently relapsing nephrotic syndrome treated with rituximab
      and subsequently mycophenolate mofetil. Both showed complete remission, which 24
      to 30 months later, was still maintained. The role of mycophenolate mofetil
      therapy in maintaining remission after successful treatment of rituximab in IgM
      nephropathy needs to be examined.

PMID- 23144103
TI  - Prevalence of asthma in urban school children in Jaipur, Rajasthan.
AB  - A cross sectional survey of 3321 school going children (5-15 years) using
      modified ISAAC questionnaire in Jaipur city showed 7.59% children to have asthma
      (in last 12 months) and 8.4% wheezing in last 12 months. Only 5.3% children had
      physician diagnosed asthma ever suggesting under diagnoses.

PMID- 23144104
TI  - Changes in biochemical contents of expressed breast milk on refrigerator storage.
AB  - To determine the biochemical integrity of refrigerated breast milk for 96 hours
      at 4C, a longitudinal observational study done with fresh milk samples. It is
      found that there were significant changes in pH, serum albumin and lactose
      concentrations in breast milk though within normal range.

PMID- 23144105
TI  - Profile of EBV associated infectious mononucleosis.
AB  - During a 5 year period, 33 children (22 males) were diagnosed to have infectious
      mononucleosis (M:F::2:1; age 9 mo-15 y).  The common clinical features observed
      were fever (100%), lymphadenopathy (84%) hepatosplenomegaly (81%), tonsillar
      enlargement (45%), neck swelling (30%), upper respiratory symptoms (21%),
      epitrochlear node enlargement (20%), vomiting and diarrhea (1%). Ten children had
      complications; upper airway obstruction and hemophagocytic lymphohistocytosis
      occurred in four each  and septic shock in two.  EBV associated infectious
      mononucleosis in hospitalized children was found to affect mainly preschool
      children and had a favorable prognosis.

PMID- 23144106
TI  - Treating pediatric liver tumors in India  a challenging proposition.

PMID- 23144107
TI  - Good outcome with ATG in aplastic anemia: welcome news, though thought-provoking!

PMID- 23144108
TI  - Eyelid myoclonia with absence seizure precipitated by carbamazepine therapy.

PMID- 23144109
TI  - Camphor poisoning.

PMID- 23144110
TI  - Widening the spectrum of services delivered by the NRC.

PMID- 23144111
TI  - Changing profile of undernutrition and edematous severe acute malnutrition
      (ESAM).

PMID- 23144112
TI  - Steroid sensitive nephrotic syndrome and steroid  toxicity: what to do next.

PMID- 23144114
TI  - Congenital lymphedema: another unique and gender specific stigmata of tuberous
      sclerosis?

PMID- 23144115
TI  - Generalized benign acanthosis nigricans.

PMID- 23144116
TI  - An infant with skin rash.

PMID- 23144117
TI  - Rowell syndrome.

PMID- 23144118
TI  - Pyogenic granuloma.

PMID- 23144119
TI  - Subjective health complaints and psychosocial work environment among university
      personnel.
AB  - BACKGROUND: Questionnaires are often used to study health problems in working
      populations. An association between self-reported symptoms and psychosocial
      strain has been suggested, but results from such studies are difficult to
      interpret, as a gender difference might be present. The knowledge in this area is
      not clear. AIMS: To compare the prevalence of subjective health symptoms and
      their relation to psychosocial work strain among men and women in different age
      groups, all working as university staff. METHODS: A cross-sectional survey was
      carried out among university personnel. The questionnaire included a subjective
      health complaint inventory consisting of 29 items about subjective somatic and
      psychological symptoms experienced during the last 30 days and psychosocial work
      factors. Regression analyses were performed. RESULTS: In total, 172 (86%) of 201
      eligible employees participated. Women had a higher prevalence of musculoskeletal
      symptoms than men. Significant differences were found between the genders for
      headaches, neck pain and arm pain. There was a significant relationship between
      musculoskeletal symptoms and work strain for both genders. This was found for
      both men and women below 40 years and among men above the age of 40. No
      significant difference was found between genders regarding pseudoneurological,
      gastrointestinal, allergic and flu-like symptoms. CONCLUSIONS: More female than
      male university personnel reported musculoskeletal symptoms. The musculoskeletal
      symptoms were associated with high work strain in both genders, but, for women,
      this was limited to employees under the age of 40. The cause of this gender
      difference is unknown.

PMID- 23144120
TI  - Acute histoplasmosis in three Mexican sewer workers.
AB  - We report the detection of high-titre anti-Histoplasma capsulatum IgM in the
      serum of three young adult males occupationally exposed to bat guano. Multidrug
      treatment with trimethoprim- sulfamethoxazole was started, followed by
      ciprofloxacin, clarithromycin, metamizole sodium,
      rifampicin/isoniazid/pyrazinamide, moxifloxacin and lastly amphotericin B and
      ceftriaxone. Despite treatment the condition of one patient deteriorated, and he
      died 23 days after exposure. The other two patients recovered after receiving
      similar therapy with the addition of voriconazole. They are currently being
      treated with itraconazole for a 1-year period.

PMID- 23144121
TI  - Energy expenditure in US automotive technicians and occupation-specific cardiac
      rehabilitation.
AB  - BACKGROUND: The standard exercise protocol for patients in a traditional cardiac
      rehabilitation (rehab) programme may not be adequate for preparing manual workers
      for a safe return to work, as these activities bear little resemblance to the
      physical movements and force exertion required in most industrial jobs. AIMS: To
      measure the energy expenditure as metabolic equivalents (METs) required for
      automotive technicians, to compare this MET level with that normally attained in
      traditional cardiac rehab programmes and to suggest cardiac rehab exercises for
      automotive technicians based on specificity of training. METHODS: Automotive
      technicians who volunteered to participate had their MET levels measured while
      they performed a defined series of work tasks in the service department of an
      automobile dealership. Their daily walking distance was also determined. RESULTS:
      Thirty-six of 95 eligible subjects participated; a response rate of 38%. Mean
      peak MET level was 7.1, less than the 8 METs target training goal often used in
      traditional cardiac rehab programmes. However, patients' outcome MET levels in
      cardiac rehab are usually measured by a treadmill stress test, whereas the
      subjects reached 7.1 METs while performing work tasks. The subjects walked an
      average of 5 km during a normal workday. CONCLUSIONS: Because MET level
      measurements are work specific, automotive technicians in a cardiac rehab
      programme should strive to reach and maintain a level of >7 METs while performing
      specific training exercises that mimic the work tasks they must do throughout the
      day. They can also benefit from traditional endurance training such as treadmill
      walking.

PMID- 23144122
TI  - Transport through graphene quantum dots.
AB  - We review transport experiments on graphene quantum dots and narrow graphene
      constrictions. In a quantum dot, electrons are confined in all lateral
      dimensions, offering the possibility for detailed investigation and controlled
      manipulation of individual quantum systems. The recently isolated two-dimensional
      carbon allotrope graphene is an interesting host to study quantum phenomena, due
      to its novel electronic properties and the expected weak interaction of the
      electron spin with the material. Graphene quantum dots are fabricated by etching
      mono-layer flakes into small islands (diameter 60-350 nm) with narrow connections
      to contacts (width 20-75 nm), serving as tunneling barriers for transport
      spectroscopy. Electron confinement in graphene quantum dots is observed by
      measuring Coulomb blockade and transport through excited states, a manifestation
      of quantum confinement. Measurements in a magnetic field perpendicular to the
      sample plane allowed to identify the regime with only a few charge carriers in
      the dot (electron-hole transition), and the crossover to the formation of the
      graphene specific zero-energy Landau level at high fields. After rotation of the
      sample into parallel magnetic field orientation, Zeeman spin splitting with a g
      factor of g ~ 2 is measured. The filling sequence of subsequent spin states is
      similar to what was found in GaAs and related to the non-negligible influence of
      exchange interactions among the electrons.

PMID- 23144123
TI  - Engineered quantum dot single-photon sources.
AB  - Fast, high efficiency and low error single-photon sources are required for the
      implementation of a number of quantum information processing applications. The
      fastest triggered single-photon sources to date have been demonstrated using
      epitaxially grown semiconductor quantum dots (QDs), which can be conveniently
      integrated with optical microcavities. Recent advances in QD technology,
      including demonstrations of high temperature and telecommunications wavelength
      single-photon emission, have made QD single-photon sources more practical. Here
      we discuss the applications of single-photon sources and their various
      requirements, before reviewing the progress made on a QD platform in meeting
      these requirements.

PMID- 23144124
TI  - Respiratory function and chemical exposures among female hairdressers in
      Palestine.
AB  - BACKGROUND: Hairdressers are exposed to chemicals and work tasks that may cause
      respiratory symptoms. There is little awareness of occupational health among
      hairdressing salons in Palestine. AIMS: To characterize respiratory symptoms,
      lung function, and knowledge of exposure to hazards among female Palestinian
      hairdressers. METHODS: Cross-sectional study of female hairdressers and controls
      of female university students and staff. Working history and respiratory symptoms
      were collected using questionnaire. Lung function was measured. Working
      conditions were characterized in salons. RESULTS: A total of 170 hairdressers
      from 56 salons and 170 controls participated. Nineteen per cent of the
      hairdressers reported wheezing versus 11% in the control group. The mean forced
      vital capacity was 3.31 l compared with 3.42 l for controls. Adjusting for age
      and height, there was a forced expiratory volume in 1 s reduction of 0.093 l (95%
      confidence interval (CI) = 0.06-0.15) comparing hairdressers with controls. A
      small number of hairdressers used respiratory protective equipment, and
      satisfactory ventilation in salons were lacking. CONCLUSIONS: Female hairdressers
      had higher prevalence of reported asthma and respiratory symptoms than the
      controls, but these differences reduced markedly when adjusted for age, height,
      weight and years of education. They had lower lung function measurements than the
      control group. Increasing the awareness of occupational health hazards and
      improving the work conditions for the hairdressers in Palestine is needed.
      Possible bias could be present as hairdressers might have over reported symptoms
      or lung function measurements might be affected by differences in socioeconomic
      status between the two groups.

PMID- 23144127
TI  - Predation response of Vibrio fischeri biofilms to bacterivorus protists.
AB  - Vibrio fischeri proliferates in a sessile, stable community known as a biofilm,
      which is one alternative survival strategy of its life cycle. Although this
      survival strategy provides adequate protection from abiotic factors, marine
      biofilms are still susceptible to grazing by bacteria-consuming protozoa.
      Subsequently, grazing pressure can be controlled by certain defense mechanisms
      that confer higher biofilm antipredator fitness. In the present work, we
      hypothesized that V. fischeri exhibits an antipredator fitness behavior while
      forming biofilms. Different predators representing commonly found species in
      aquatic populations were examined, including the flagellates Rhynchomonas nasuta
      and Neobodo designis (early biofilm feeders) and the ciliate Tetrahymena
      pyriformis (late biofilm grazer). V. fischeri biofilms included isolates from
      both seawater and squid hosts (Euprymna and Sepiola species). Our results
      demonstrate inhibition of predation by biofilms, specifically, isolates from
      seawater. Additionally, antiprotozoan behavior was observed to be higher in late
      biofilms, particularly toward the ciliate T. pyriformis; however, inhibitory
      effects were found to be widespread among all isolates tested. These results
      provide an alternative explanation for the adaptive advantage and persistence of
      V. fischeri biofilms and provide an important contribution to the understanding
      of defensive mechanisms that exist in the out-of-host environment.

PMID- 23144128
TI  - Combinatorial mutagenesis and selection of improved signal sequences and their
      application for high-level production of translocated heterologous proteins in
      Escherichia coli.
AB  - We previously designed the consensus signal peptide (CSP) and demonstrated that
      it can be used to strongly stimulate heterologous protein production in
      Escherichia coli. A comparative study using CSP and two bacterial signal
      sequences, pelB and ompA, showed that the effect of signal sequences on both
      expression level and translocation efficiency can be highly protein specific. We
      report here the generation of CSP mutant libraries by a combinatorial mutagenesis
      approach. Degenerated CSP oligonucleotides were cloned in frame with the 5' end
      of the bla gene, encoding the mature periplasmic beta-lactamase released from its
      native signal sequence. This novel design allows for a direct selection of
      improved signal sequences that positively affect the expression level and/or
      translocation efficiency of beta-lactamase, based on the ampicillin tolerance
      level of the E. coli host cells. By using this strategy, 61 different CSP mutants
      with up to 8-fold-increased ampicillin tolerance level and up to 5.5-fold
      increased beta-lactamase expression level were isolated and characterized
      genetically. A subset of the CSP mutants was then tested with the alternative
      reporter gene phoA, encoding periplasmic alkaline phosphatase (AP), resulting in
      an up to 8-fold-increased production level of active AP protein in E. coli.
      Moreover, it was demonstrated that the CSP mutants can improve the production of
      the medically important human interferon alpha2b under high-cell-density
      cultivations. Our results show that there is a clear potential for improving
      bacterial signal sequences by using combinatorial mutagenesis, and bioinformatics
      analyses indicated that the beneficial mutations could not be rationally
      predicted.

PMID- 23144129
TI  - Characterization of a newly discovered symbiont of the whitefly Bemisia tabaci
      (Hemiptera: Aleyrodidae).
AB  - Bemisia tabaci (Hemiptera: Aleyrodidae) is a species complex containing >28
      cryptic species, some of which are important crop pests worldwide. Like many
      other sap-sucking insects, whiteflies harbor an obligatory symbiont, "Candidatus
      Portiera aleyrodidarum," and a number of secondary symbionts. So far, six genera
      of secondary symbionts have been identified in B. tabaci. In this study, we
      report and describe the finding of an additional bacterium in the indigenous B.
      tabaci cryptic species China 1 (formerly known as B. tabaci biotype ZHJ3).
      Phylogenetic analysis based on the 16S rRNA and gltA genes showed that the
      bacterium belongs to the Alphaproteobacteria subdivision of the Proteobacteria
      and has a close relationship with human pathogens of the genus Orientia.
      Consequently, we temporarily named it Orientia-like organism (OLO). OLO was found
      in six of eight wild populations of B. tabaci China 1, with the infection rate
      ranging from 46.2% to 76.8%. Fluorescence in situ hybridization (FISH) of B.
      tabaci China 1 in nymphs and adults revealed that OLOs are confined to the
      bacteriome and co-occur with "Ca. Portiera aleyrodidarum." The vertical
      transmission of OLO was demonstrated by detection of OLO at the anterior pole end
      of the oocytes through FISH. Quantitative PCR analysis of population dynamics
      suggested a complex interaction between "Ca. Portiera aleyrodidarum" and OLO.
      Based on these results, we propose "Candidatus Hemipteriphilus asiaticus" for the
      classification of this symbiont from B. tabaci.

PMID- 23144130
TI  - Comparative analysis of Leptospira strains isolated from environmental soil and
      water in the Philippines and Japan.
AB  - There have been few reports on the epidemiological analysis of environmental
      Leptospira isolates. This is probably because the isolation of leptospires from
      the environment was usually unsuccessful due to the overgrowth of contaminants
      and the slow growth of Leptospira. In this study, we collected a total of 88
      samples of soil and water from three sites: Metro Manila and Nueva Ecija,
      Philippines (an area where Leptospira is now endemic), and Fukuoka, Japan (an
      area where Leptospira was once endemic). We succeeded in isolating Leptospira
      from 37 samples by using the novel combination of five antimicrobial agents
      reported in 2011. The frequencies of positive isolation of Leptospira in the
      Philippines and Japan were 40 and 46%, respectively. For Leptospira-positive
      samples, five colonies from each sample were isolated and analyzed by pulsed
      field gel electrophoresis (PFGE). The isolates from each area showed their
      respective characteristics in phylogenetic trees based on the PFGE patterns. Some
      isolates were closely related to each other across borders. Based on 16S rRNA
      gene-based phylogenetic analysis, four isolates in Fukuoka were identified as a
      pathogenic species, L. alstonii; however, its virulence had been lost. One
      isolate from Nueva Ecija was identified as the intermediate pathogenic species
      Leptospira licerasiae. Most of the isolates from the environment belonged to
      nonpathogenic Leptospira species. We also investigated the strain variation among
      the isolates in a puddle over 5 months. We demonstrated, using PFGE analysis,
      that Leptospira survived in the wet soil on dry days and appeared in the surface
      water on rainy days. These results showed that the soil could be a reservoir of
      leptospires in the environment.

PMID- 23144131
TI  - Physiological and metabolic effects of carbon monoxide oxidation in the model
      marine bacterioplankton Ruegeria pomeroyi DSS-3.
AB  - Ruegeria pomeroyi expresses carbon monoxide (CO) dehydrogenase and oxidizes CO;
      however, CO has no effect on growth. Nuclear magnetic resonance (NMR) spectra
      showed that CO has no effect on cellular metabolite profiles. These data support
      ecosystem models proposing that, even though bacterioplankton CO oxidation is
      biogeochemically significant, it has an insignificant effect on bacterioplankton
      productivity.

PMID- 23144132
TI  - Identification of gold nanoparticle-resistant mutants of Saccharomyces cerevisiae
      suggests a role for respiratory metabolism in mediating toxicity.
AB  - Positively charged gold nanoparticles (0.8-nm core diameter) reduced yeast
      survival, but not growth, at a concentration of 10 to 100 MUg/ml. Among 17
      resistant deletion mutants isolated in a genome-wide screen, highly significant
      enrichment was observed for respiration-deficient mutants lacking genes encoding
      proteins associated with the mitochondrion.

PMID- 23144133
TI  - Influence of Salmonella enterica serovar enteritidis infection on the development
      of the cecum microbiota in newly hatched chicks.
AB  - Terminal restriction fragment length polymorphism and quantitative PCR showed
      that the cecal microbiota of chicks up to the age of 21 days was dominated by
      representatives of the orders Enterobacteriales, Clostridiales, and
      Lactobacillales. Salmonella enterica serovar Enteritidis infection caused the
      greatest changes in the gut microbiota when 1-day-old chicks were infected,
      compared with the infection of 4- and 16-day-old chicks.

PMID- 23144134
TI  - Induction of nitrate-dependent Fe(II) oxidation by Fe(II) in Dechloromonas sp.
      strain UWNR4 and Acidovorax sp. strain 2AN.
AB  - We evaluated the inducibility of nitrate-dependent Fe(II)-EDTA oxidation (NDFO)
      in non-growth, chloramphenicol-amended, resting-cell suspensions of Dechloromonas
      sp. strain UWNR4 and Acidovorax sp. strain 2AN. Cells previously incubated with
      Fe(II)-EDTA oxidized ca. 6-fold more Fe(II)-EDTA than cells previously incubated
      with Fe(III)-EDTA. This is the first report of induction of NDFO by Fe(II).

PMID- 23144135
TI  - Clostridium carboxidivorans strain P7T recombinant formate dehydrogenase
      catalyzes reduction of CO(2) to formate.
AB  - Recombinant formate dehydrogenase from the acetogen Clostridium carboxidivorans
      strain P7(T), expressed in Escherichia coli, shows particular activity towards
      NADH-dependent carbon dioxide reduction to formate due to the relative binding
      affinities of the substrates and products. The enzyme retains activity over 2
      days at 4 degrees C under oxic conditions.

PMID- 23144136
TI  - Heterologous carotenoid-biosynthetic enzymes: functional complementation and
      effects on carotenoid profiles in Escherichia coli.
AB  - A limited number of carotenoid pathway genes from microbial sources have been
      studied for analyzing the pathway complementation in the heterologous host
      Escherichia coli. In order to systematically investigate the functionality of
      carotenoid pathway enzymes in E. coli, the pathway genes of carotenogenic
      microorganisms (Brevibacterium linens, Corynebacterium glutamicum, Rhodobacter
      sphaeroides, Rhodobacter capsulatus, Rhodopirellula baltica, and Pantoea
      ananatis) were modified to form synthetic expression modules and then were
      complemented with Pantoea agglomerans pathway enzymes (CrtE, CrtB, CrtI, CrtY,
      and CrtZ). The carotenogenic pathway enzymes in the synthetic modules showed
      unusual activities when complemented with E. coli. For example, the expression of
      heterologous CrtEs of B. linens, C. glutamicum, and R. baltica influenced P.
      agglomerans CrtI to convert its substrate phytoene into a rare product-3,4,3',4'
      tetradehydrolycopene-along with lycopene, which was an expected product,
      indicating that CrtE, the first enzyme in the carotenoid biosynthesis pathway,
      can influence carotenoid profiles. In addition, CrtIs of R. sphaeroides and R.
      capsulatus converted phytoene into an unusual lycopene as well as into
      neurosporene. Thus, this study shows that the functional complementation of
      pathway enzymes from different sources is a useful methodology for diversifying
      biosynthesis as nature does.

PMID- 23144137
TI  - Landscape and meteorological factors affecting prevalence of three food-borne
      pathogens in fruit and vegetable farms.
AB  - Produce-related outbreaks have been traced back to the preharvest environment. A
      longitudinal study was conducted on five farms in New York State to characterize
      the prevalence, persistence, and diversity of food-borne pathogens in fresh
      produce fields and to determine landscape and meteorological factors that predict
      their presence. Produce fields were sampled four times per year for 2 years. A
      total of 588 samples were analyzed for Listeria monocytogenes, Salmonella, and
      Shiga toxin-producing Escherichia coli (STEC). The prevalence measures of L.
      monocytogenes, Salmonella, and STEC were 15.0, 4.6, and 2.7%, respectively. L.
      monocytogenes and Salmonella were detected more frequently in water samples,
      while STEC was detected with equal frequency across all sample types (soil,
      water, feces, and drag swabs). L. monocytogenes sigB gene allelic types 57, 58,
      and 61 and Salmonella enterica serovar Cerro were repeatedly isolated from water
      samples. Soil available water storage (AWS), temperature, and proximity to three
      land cover classes (water, roads and urban development, and pasture/hay grass)
      influenced the likelihood of detecting L. monocytogenes. Drainage class, AWS, and
      precipitation were identified as important factors in Salmonella detection. This
      information was used in a geographic information system framework to hypothesize
      locations of environmental reservoirs where the prevalence of food-borne
      pathogens may be elevated. The map indicated that not all croplands are equally
      likely to contain environmental reservoirs of L. monocytogenes. These findings
      advance recommendations to minimize the risk of preharvest contamination by
      enhancing models of the environmental constraints on the survival and persistence
      of food-borne pathogens in fields.

PMID- 23144138
TI  - The mangotoxin biosynthetic operon (mbo) is specifically distributed within
      Pseudomonas syringae genomospecies 1 and was acquired only once during evolution.
AB  - Mangotoxin production was first described in Pseudomonas syringae pv. syringae
      strains. A phenotypic characterization of 94 P. syringae strains was carried out
      to determine the genetic evolution of the mangotoxin biosynthetic operon (mbo).
      We designed a PCR primer pair specific for the mbo operon to examine its
      distribution within the P. syringae complex. These primers amplified a 692-bp DNA
      fragment from 52 mangotoxin-producing strains and from 7 non-mangotoxin-producing
      strains that harbor the mbo operon, whereas 35 non-mangotoxin-producing strains
      did not yield any amplification. This, together with the analysis of draft
      genomes, allowed the identification of the mbo operon in five pathovars
      (pathovars aptata, avellanae, japonica, pisi, and syringae), all of which belong
      to genomospecies 1, suggesting a limited distribution of the mbo genes in the P.
      syringae complex. Phylogenetic analyses using partial sequences from housekeeping
      genes differentiated three groups within genomospecies 1. All of the strains
      containing the mbo operon clustered in groups I and II, whereas those lacking the
      operon clustered in group III; however, the relative branching order of these
      three groups is dependent on the genes used to construct the phylogeny. The mbo
      operon maintains synteny and is inserted in the same genomic location, with high
      sequence conservation around the insertion point, for all the strains in groups I
      and II. These data support the idea that the mbo operon was acquired horizontally
      and only once by the ancestor of groups I and II from genomospecies 1 within the
      P. syringae complex.

PMID- 23144139
TI  - Impact of long-term diesel contamination on soil microbial community structure.
AB  - Microbial community composition and diversity at a diesel-contaminated railway
      site were investigated by pyrosequencing of bacterial and archaeal 16S rRNA gene
      fragments to understand the interrelationships among microbial community
      composition, pollution level, and soil geochemical and physical properties. To
      this end, 26 soil samples from four matrix types with various geochemical
      characteristics and contaminant concentrations were investigated. The presence of
      diesel contamination significantly impacted microbial community composition and
      diversity, regardless of the soil matrix type. Clean samples showed higher
      diversity than contaminated samples (P < 0.001). Bacterial phyla with high
      relative abundances in all samples included Proteobacteria, Firmicutes,
      Actinobacteria, Acidobacteria, and Chloroflexi. High relative abundances of
      Archaea, specifically of the phylum Euryarchaeota, were observed in contaminated
      samples. Redundancy analysis indicated that increased relative abundances of the
      phyla Chloroflexi, Firmicutes, and Euryarchaeota correlated with the presence of
      contamination. Shifts in the chemical composition of diesel constituents across
      the site and the abundance of specific operational taxonomic units (OTUs; defined
      using a 97% sequence identity threshold) in contaminated samples together suggest
      that natural attenuation of contamination has occurred. OTUs with sequence
      similarity to strictly anaerobic Anaerolineae within the Chloroflexi, as well as
      to Methanosaeta of the phylum Euryarchaeota, were detected. Anaerolineae and
      Methanosaeta are known to be associated with anaerobic degradation of oil-related
      compounds; therefore, their presence suggests that natural attenuation has
      occurred under anoxic conditions. This research underscores the usefulness of
      next-generation sequencing techniques both to understand the ecological impact of
      contamination and to identify potential molecular proxies for detection of
      natural attenuation.

PMID- 23144140
TI  - Taking the starch out of oral biofilm formation: molecular basis and functional
      significance of salivary alpha-amylase binding to oral streptococci.
AB  - alpha-Amylase-binding streptococci (ABS) are a heterogeneous group of commensal
      oral bacterial species that comprise a significant proportion of dental plaque
      microfloras. Salivary alpha-amylase, one of the most abundant proteins in human
      saliva, binds to the surface of these bacteria via specific surface-exposed alpha
      amylase-binding proteins. The functional significance of alpha-amylase-binding
      proteins in oral colonization by streptococci is important for understanding how
      salivary components influence oral biofilm formation by these important dental
      plaque species. This review summarizes the results of an extensive series of
      studies that have sought to define the molecular basis for alpha-amylase binding
      to the surface of the bacterium as well as the biological significance of this
      phenomenon in dental plaque biofilm formation.

PMID- 23144142
TI  - Multiplex PCR assay targeting a diguanylate cyclase-encoding gene, cgcA, to
      differentiate species within the genus Cronobacter.
AB  - In a comparison to the widely used Cronobacter rpoB PCR assay, a highly specific
      multiplexed PCR assay based on cgcA, a diguanylate cyclase gene, that identified
      all of the targeted six species among 305 Cronobacter isolates was designed. This
      assay will be a valuable tool for identifying suspected Cronobacter isolates from
      food-borne investigations.

PMID- 23144141
TI  - Osmoprotection of Bacillus subtilis through import and proteolysis of proline
      containing peptides.
AB  - Bacillus subtilis can attain cellular protection against the detrimental effects
      of high osmolarity through osmotically induced de novo synthesis and uptake of
      the compatible solute l-proline. We have now found that B. subtilis can also
      exploit exogenously provided proline-containing peptides of various lengths and
      compositions as osmoprotectants. Osmoprotection by these types of peptides is
      generally dependent on their import via the peptide transport systems (Dpp, Opp,
      App, and DtpT) operating in B. subtilis and relies on their hydrolysis to
      liberate proline. The effectiveness with which proline-containing peptides confer
      osmoprotection varies considerably, and this can be correlated with the amount of
      the liberated and subsequently accumulated free proline by the osmotically
      stressed cell. Through gene disruption experiments, growth studies, and the
      quantification of the intracellular proline pool, we have identified the PapA
      (YqhT) and PapB (YkvY) peptidases as responsible for the hydrolysis of various
      types of Xaa-Pro dipeptides and Xaa-Pro-Xaa tripeptides. The PapA and PapB
      peptidases possess overlapping substrate specificities. In contrast,
      osmoprotection by peptides of various lengths and compositions with a proline
      residue positioned at their N terminus was not affected by defects in the PapA
      and PapB peptidases. Taken together, our data provide new insight into the
      physiology of the osmotic stress response of B. subtilis. They illustrate the
      flexibility of this ubiquitously distributed microorganism to effectively exploit
      environmental resources in its acclimatization to sustained high-osmolarity
      surroundings through the accumulation of compatible solutes.

PMID- 23144145
TI  - Alzheimer's disease--emerging new potential therapeutic modalities.

PMID- 23144143
TI  - A new, sensitive marine microalgal recombinant biosensor using luminescence
      monitoring for toxicity testing of antifouling biocides.
AB  - In this study, we propose the use of the marine green alga Ostreococcus tauri,
      the smallest free-living eukaryotic cell known to date, as a new luminescent
      biosensor for toxicity testing in the environment. Diuron and Irgarol 1051, two
      antifouling biocides commonly encountered in coastal waters, were chosen to test
      this new biosensor along with two degradation products of diuron. The effects of
      various concentrations of the antifoulants on four genetic constructs of O. tauri
      (based on genes involved in photosynthesis, cell cycle, and circadian clock) were
      compared using 96-well culture microplates and a luminometer to automatically
      measure luminescence over 3 days. This was compared to growth inhibition of O.
      tauri wild type under the same conditions. Luminescence appeared to be more
      sensitive than growth inhibition as an indicator of toxicity. Cyclin-dependent
      kinase (CDKA), a protein involved in the cell cycle, fused to luciferase (CDKA
      Luc) was found to be the most sensitive of the biosensors, allowing an accurate
      determination of the 50% effective concentration (EC(50)) after only 2 days
      (diuron, 5.65 +/- 0.44 MUg/liter; Irgarol 1015, 0.76 +/- 0.10 MUg/liter). The
      effects of the antifoulants on the CDKA-Luc biosensor were then compared to
      growth inhibition in natural marine phytoplankton. The effective concentrations
      of diuron and Irgarol 1051 were found to be similar, indicating that this
      biosensor would be suitable as a reliable ecotoxicological test. The advantage of
      this biosensor over cell growth inhibition testing is that the process can be
      easily automated and could provide a high-throughput laboratory approach to
      perform short-term toxicity tests. The ability to genetically transform and
      culture recombinant O. tauri gives it huge potential for screening many other
      toxic compounds.

PMID- 23144146
TI  - Direct thrombin inhibitors' potential efficacy in Alzheimer's disease.
AB  - Alzheimer's disease (AD) is a neurodegenerative disease with no available disease
      modifying drugs. However, it has been postulated that neurovascular damage is a
      primary occurrence in this disease. Neurovascular damage is the result of the
      presence of cardiovascular risk factor generating hypoxia, oxidative stress, and
      metabolic changes that activate the endothelial cells of the brain
      microvasculature in order to respond to the stress by the development of
      angiogenesis. This endothelial activation could lead to a secretion of many
      proinflammatory cytokines and growth factors, such as thrombin. Heparin and
      related oligosaccharides have been shown to be efficient in the improvement of
      symptoms of AD. Their efficacy may be limited by their nonselective inhibitory
      effect of thrombin's activity. Direct thrombin inhibitors, such as dabigatran,
      might be efficient in the treatment of patients with AD because of their high
      selectivity for thrombin's activity inhibition while having a safer side effects
      profile than heparin.

PMID- 23144147
TI  - Predicting attendance at dementia family support groups.
AB  - This longitudinal study examined the predictors of dementia family caregivers'
      self-reported attendance at support group meetings over 6 months. First-time
      attendees were contacted by telephone after their first meeting and assessed for
      (a) perceptions of similarity between themselves and other members, (b)
      depressive symptoms, and (c) perceptions of social support from the facilitator
      and other members. Participants (N = 70) were recontacted 6 months later to
      obtain self-reports of attendance patterns. Self-reported attendance at any
      meeting during this follow-up period was predicted by perceived similarity in
      care recipient's stage of dementia and perceived support from group members as
      assessed at the first interview. Greater perceived support from group members and
      fewer depressive symptoms at time 1 predicted a higher frequency of support group
      attendance over the follow-up period. Results have implications for orienting new
      support group members as well as training and supporting group facilitators.

PMID- 23144149
TI  - Occupational allergic rhinoconjunctivitis and bronchial asthma induced by goat
      cheese.

PMID- 23144150
TI  - The analysis of volatile organic compounds biomarkers for lung cancer in exhaled
      breath, tissues and cell lines.
AB  - BACKGROUND: Volatile organic compounds (VOCs) biomarkers in breath provide a
      novel, noninvasive and quick approach to diagnosis lung cancer. The aim of the
      proposed study was to investigate the VOCs biomarkers in exhaled breath for lung
      cancer. METHOD: The VOCs in exhaled breath of 88 lung cancer patients, 70 lung
      benign disease and 85 healthy people were analyzed by Solid Phase Micro
      Extraction - Gas Chromatography Mass Spectrometry (SPME-GCMS). Three types of
      lung cancer cells and 18 lung cancer patients' tissues were cultured in vitro.
      The VOCs in the headspace of these cultivations were analyzed as an evidence of
      production mechanism of the VOCs in breath. Three lung cancer diagnosis models
      were constructed respectively in exhaled breath samples using Linear Discriminant
      Analysis (LDA). Leave one out cross validation was employed to evaluate these
      models. RESULTS: 23 VOCs, whose areas under curve (AUC) of receiver operating
      characteristic (ROC) > 0.60 and p < 0.01, were confirmed as the VOCs biomarkers
      for lung cancer. Three diagnostic models based on 23 VOCs could easily
      discriminate lung cancer patients from controls with 96.47% sensitivity and
      97.47% specificity. However, the discrimination between early stage and later
      stage lung cancer was not very obvious.

PMID- 23144151
TI  - Suppression of Zinc Finger Homeobox 3 expression in tumor cells decreases the
      survival rate among non-small cell lung cancer patients.
AB  - Zinc Finger Homeobox 3 (ZFHX3) was first identified as a suppressor of alpha
      fetoprotein gene and is a good candidate for the 16q22 tumor suppressor. In this
      study we investigated the relationship between tumoral ZFHX3 mRNA expression and
      the clinicopathological characteristics of patients with non-small cell lung
      cancer (NSCLC). We used semi-quantitative real time reverse transcription
      polymerase chain reaction to assess expression of ZFHX3 mRNA in tumor samples
      from 140 patients with NSCLC. We found that the 5-year overall survival rate
      among patients weakly expressing ZFHX3 was significantly poorer than among those
      expressing higher levels of ZFHX3 (P< 0.0001 by log-rank test). Multivariate
      logistic regression analysis revealed being lower ZFHX3 expression are
      independent predictors of lymph node metastasis. With low-ZFHX3 tumors, there was
      a significantly (P=0.009) greater (7.39-fold higher) risk of lymph node
      metastasis. Multivariate Cox proportional hazard analyses revealed that being
      lower ZFHX3 expression (Hazard ratio, 4.42; 95% CI, 2.09-8.92; p=0.0002) were
      independent factors affecting 5-year overall survival. Ratio of ZFHX3 mRNA in
      tumor against normal lung in low-ZFHX3 tumor was lower than in high-ZFHX3 tumor.
      In conclusion, suppression of ZFHX3 expression in tumor cells decreases the
      survival rate among patients with NSCLC.

PMID- 23144152
TI  - The interaction between RAGE gene polymorphisms and HPV infection in determining
      the susceptibility of cervical cancer in a Chinese population.
AB  - AIM: To explore the possible association between the receptor for advanced
      glycation end products (RAGE) gene polymorphisms and the risk of cervical cancer.
      METHOD: We enrolled 488 patients with cervical squamous cell carcinoma and 715
      age-matched female healthy subjects as controls. Human Papillomavirus (HPV)
      infection and four RAGE gene polymorphisms (-429T>C, -374T>A, 1704G>T, and 82G>S)
      in all subjects were determined. RESULTS: The genotype distributions and allele
      frequencies of -429T>C, 1704 T>G and -374T>A were not significantly different
      between cervical cancer patients and controls (all P> 0.05). For 82G>S
      polymorphisms, the genotype distributions and allele frequencies were
      significantly different between the two groups. The cervical cancer patients had
      markedly higher percentage of 82SS carriage than controls. The logistic
      regression analysis showed that the 82SS genotype was associated with
      significantly elevated risk for cervical cancer, adjusted odds ratio (OR) was
      1.98, (P< 0.001). In addition, the 82SS carriers had significantly lower serum
      soluble RAGE (sRAGE) levels than 82GS and 82GG. The polymorphisms of -429T>C, 
      374T>A and 1704T>G did not affect the cervical cancer risk and the serum sRAGE
      levels. When all the cancer patients were stratified by HPV infection status, the
      82GS and 82SS genotype carriers in the HPV infection subgroup had increased risk
      for cervical cancer versus 82GG (OR=1.68 and 1.74, respectively, both P<0.05).
      This trend was not observed in the subgroup with no detectable HPV DNA.
      CONCLUSION: Our results suggest that the RAGE 82G>S polymorphisms, interacting
      with HPV infection, are implicated in the occurrence of cervical cancer.

PMID- 23144153
TI  - Association between newly identified variant form of DNA polymerase beta (Delta
      208-304) and ovarian cancer.
AB  - BACKGROUND: Base excision repair (BER) is a key pathway for maintaining genomic
      stability. A key enzyme in the BER pathway is DNA polymerase beta (polbeta),
      which removes the deoxyribose phosphate group (dRP) and fills in the gap with a
      nucleotide after the DNA lesion is excised. It has been shown that more than
      thirty percent of breast, bladder, esophageal, colon, and gastric cancer samples
      studied so far have exhibited DNA polymerase beta mutation. AIM: To examine the
      association between polbeta polymorphism and ovarian cancer, case control study
      was performed using one hundred fifty two cancer samples and non-metastatic
      normal samples from the same patients in Indian population. DESIGN: The polbeta
      polymorphism was studied in ovarian carcinoma tissues samples initially by RT-PCR
      followed by sequencing and then by western blot analysis. RESULT: A new type of
      variant was detected along with the WT allele (polbetaDelta<formula> _{208
      304}</formula>). Stage IV samples have shown a significant factor for cancer
      progression in ovarian cancer patients of India [OR=3.58; 95% CI (1.6-7.9); and
      p=0.001]. The association study involving serous type and the variant showed a
      tendency towards ovarian carcinogenesis [OR=1.57; 95% CI (0.8-3.1); p=0.19]. The
      western blot analysis result indicates that the specific deletion appears to be
      associated with disease progression. CONCLUSION: The result reveals that this
      variant form of polbeta is a predisposing factor for stage IV ovarian cancer
      samples in Indian population.

PMID- 23144154
TI  - Interleukin-6 and oncostatin M are elevated in liver disease in conjunction with
      candidate hepatocellular carcinoma biomarker GP73.
AB  - The Golgi phosphoprotein GP73 is elevated in the circulation of individuals with
      a diagnosis of hepatocellular carcinoma. Its usefulness as a biomarker of HCC is
      questioned, since it has also been reported to be elevated in the circulation of
      people with liver cirrhosis. Regulation of GP73 by inflammatory cytokines is
      therefore of interest. The interleukin-6 (IL-6) family cytokines were tested for
      effects on GP73 mRNA and/or protein levels in human hepatoblastoma HepG2 cells.
      Levels of GP73 mRNA and protein were up-regulated in HepG2 cells following
      treatment with either proinflammatory cytokine IL-6 or the related cytokine
      oncostatin M (OSM). Induction required the shared receptor subunit gp130, and
      correlated with increased tyrosine phosphorylation of STAT3. Maximal cytokine
      mediated induction was not observed in the presence of protein synthesis
      inhibitor cycloheximide, suggesting additional regulatory factors play an
      important role. ELISA measurement of GP73 and IL-6 levels in the sera of patients
      with pre-malignant liver disease revealed a significant correlation between
      circulating levels of the two proteins. Similarly, a sensitive ELISA assay was
      developed to measure circulating OSM. OSM levels were elevated 6-7 fold in sera
      from patients with either cirrhosis or HCC relative to controls without liver
      disease. Although there was an association between levels of GP73 and OSM in
      serum from people with liver cirrhosis, there was not a statistically significant
      correlation in HCC, suggesting that the role of the cytokines in determining
      circulating levels may be complex. To our knowledge, this is the first report of
      OSM elevation being associated with liver disease.

PMID- 23144155
TI  - Serum concentrations of human chorionic gonadotropin beta and its association
      with survival in patients with colorectal cancer.
AB  - Increased serum concentrations of the beta subunit of human chorionic
      gonadotropin (hCGbeta) are associated with adverse prognosis in several cancers.
      The aim of the present study was to analyse the association between serum hCGbeta
      recurrence, and survival, in patients with colorectal cancer. The concentrations
      of hCGbeta were determined in serum collected preoperatively from 324 patients
      with colorectal cancer, of whom 270 were curatively treated. The serum
      concentrations of hCGbeta were associated with increasing age and they were
      higher in women than in men. Using the 75th percentile (1.55 pmol/L) as a cut-off
      for serum hCGbeta, overall survival (OS) was shorter in patients with elevated
      concentrations (HR 1.95; 95% CI 1.39-2.74; P=0.004), and this association was
      stronger in women (P=0.022) than in men (P=0.061). In multivariate analyses
      including age, disease stage, tumour differentiation, vascular invasion and CEA,
      high serum hCGbeta concentrations remained an independent prognostic factor for
      adverse OS in women (HR 2.26; 95%CI 1.39-3.67), but not in men (HR 0.78; 95%CI
      0.41-1.51). The same trend was observed for disease free- and cancer specific
      survival. High serum concentration of hCGbeta is an independent prognostic factor
      for adverse outcome in women with colorectal cancer.

PMID- 23144156
TI  - Drug sensitivity and sphingolipid metabolism in CLL.

PMID- 23144157
TI  - CML: the good, the better, and the difficult choices.

PMID- 23144158
TI  - TP53 mutations and rituximab-CHOP.

PMID- 23144159
TI  - Monitoring granule traffic in megakaryocytes.

PMID- 23144160
TI  - Contact with stroke.

PMID- 23144161
TI  - Ultrasonographic measurement of the distal femoral cartilage thickness in
      patients with unilateral transtibial amputation.
AB  - BACKGROUND: Lower limb amputation sometimes predisposes to degenerative secondary
      disorders. OBJECTIVES: To evaluate the distal femoral cartilage thicknesses of
      patients with unilateral transtibial amputations using ultrasound and to
      investigate the relationship between cartilage thickness and disease-related
      parameters. STUDY DESIGN: Cross-sectional study. METHODS: Twenty-four unilateral
      transtibial amputees (mean age: 46.4 +/- 8.5 years, range: 28-60 years) were
      evaluated. Duration of prosthesis use (years) and daily walking time with
      prosthesis (hours) were recorded. Functional status was assessed by gate velocity
      (m/s), and 6-min walking distance (m) with prosthesis. Ultrasound was used to
      measure distal femoral cartilage thicknesses bilaterally at medial/lateral
      condyles and the intercondylar areas. The percentages of cartilage loss (of the
      amputee-side in comparison with the nonamputee-side) were calculated. RESULTS:
      Compared to the nonamputee-sides, distal femoral cartilage was significantly
      thinner at lateral condyles and the intercondylar areas on the amputee-sides (p <
      0.05). Significant positive correlations were detected between the percentage of
      cartilage loss (at all three sites of measurement) and gate velocity, 6-min
      walking distance, and daily walking time with prosthesis (all p < 0.05).
      CONCLUSIONS: Future prospective controlled studies are warranted to determine the
      principles of optimum prosthetic use regarding its possible effects on the
      femoral cartilage of amputee patients. CLINICAL RELEVANCE: The correlations
      between the cartilage loss in the amputee extremity with faster gait and longer
      daily prosthetic use suggest that abnormal gait patterns might increase the
      loading on the amputated extremity.

PMID- 23144162
TI  - Face-protective orthosis in sport-related injuries.
AB  - BACKGROUND AND AIM: Sport is associated with risk of injury and re-injury. A
      rehabilitative sport-related orthosis could protect the injured site and help in
      the earlier return of athlete to the match. This technical note aims to describe
      a potential high-prescribed face orthosis to protect/prevent a sport-related
      injury. TECHNIQUE: Face-protective orthosis should be custom molded from negative
      impression of the injured athlete's face. It is lightweight and structured as a
      one-piece rigid plastic shell that is secured in place with three elastic straps.
      Due to the diverse patterns of craniomaxillofacial injuries, the shape, length,
      trimline, and characteristics of face-protective orthoses could be different.
      DISCUSSION: Face-protective orthoses could have prophylactic or rehabilitative
      roles according to task and prescription reason. Although the main action of the
      facial orthoses should be protection, the design of the face-protective orthosis
      should be improved both functionality and aesthetically to promote its use by
      athletes. CLINICAL RELEVANCE: The craniomaxillofacial injuries have potential to
      be treated by custom-molded face-protective orthoses. These orthoses could have
      prophylactic or rehabilitative roles based on their prescription purpose. These
      orthoses could cause earlier return of athletes to sports matches.

PMID- 23144163
TI  - Erythrocyte aggregation portends worse outcomes in unstable angina patients
      undergoing percutaneous coronary interventions.
AB  - OBJECTIVE: The positive correlation between the time from symptom onset to the
      appearance of an inflammatory response and erythrocyte aggregation (EA) in the
      peripheral blood of acute coronary syndromes (ACS) patients had been previously
      reported by us. We now analyze the added prognostic value of EA in ACS patients
      undergoing percutaneous coronary interventions (PCI). METHODS: We performed an
      analysis on prospectively collected data at a tertiary hospital catheterization
      laboratory between 2006-2011. Cox regression models were fitted for EA cut-offs
      and performed separately for myocardial infarction (MI) and unstable angina
      pectoris (UAP) patients. Major adverse cardiovascular events (MACE) were defined
      as all-cause mortality, MI and stroke. Follow up time was defined as the time
      from PCI to either MACE or November 20, 2011. RESULTS: Included were 1055
      patients (637 with MI and 418 with UAP). The median follow up in the MI and the
      UAP groups was 14 and 15 months, respectively (maximal follow up of 4.1 years).
      In the UAP group there was a significant increase in the MACE for the group with
      high EA (HR = 2.3, p = 0.04) compared to the group of patients with low EA. This
      was not found for patients presenting with MI. CONCLUSIONS: Elevated EA portends
      worse outcomes in UAP patients undergoing PCI.

PMID- 23144164
TI  - Trends in the utilisation of psychotropic medications in Australia from 2000 to
      2011.
AB  - OBJECTIVE: This study examined longitudinal trends in the dispensing of
      psychotropic medications in Australia from January 2000 to December 2011. METHOD:
      Dispensing data for the major classes of psychotropic medications
      (antidepressants, anxiolytics, sedatives, antipsychotics, mood stabilisers and
      attention-deficit hyperactivity disorder (ADHD) medications) were obtained from
      the Drug Utilisation Sub-Committee of the Australian Department of Health and
      Ageing. Results were expressed in terms of defined daily doses/1000
      population/day (DDDs/1000/day). RESULTS: There was a 58.2% increase in the
      dispensing of psychotropic drugs in Australia from 2000 to 2011, driven by major
      increases in antidepressants (95.3% increase in DDDs/1000/day), atypical
      antipsychotics (217.7% increase) and ADHD medications (72.9% increase).
      Dispensing of anxiolytics remained largely unchanged, while sedatives and typical
      antipsychotics decreased by 26.4% and 61.2%, respectively. Lithium dispensing
      remained static while valproate and lamotrigine increased markedly. In 2011,
      antidepressants accounted for 66.9% of total psychotropic DDDs/1000/day totals,
      far greater than anxiolytics (11.4%), antipsychotics (7.3%), mood stabilisers
      (5.8%), sedatives (5.5%), or ADHD medications (3.0%). Sertraline, olanzapine,
      valproate and methylphenidate were the most frequently dispensed antidepressant,
      antipsychotic, mood stabiliser and ADHD medication, respectively, while diazepam
      and temazepam were the most commonly dispensed anxiolytic and sedative.
      CONCLUSIONS: Psychotropic utilisation markedly increased in Australia between
      2000 and 2011. Some potential concerns include: (1) the continuing high use of
      benzodiazepines, particularly alprazolam, despite their problematic effects; (2)
      the rapid increase in serotonin noradrenaline reuptake inhibitor (SNRI) use,
      given their more complex side-effect profile relative to selective serotonin
      reuptake inhibitors (SSRIs); and (3) the dramatic increase in antidepressant
      prescriptions despite questions about the efficacy of these drugs in mild to
      moderate depression. Finally, some limitations are identified regarding use of
      the DDDs/1000/day metric, which can distort estimates of utilisation of specific
      drugs when the defined daily dose is higher or lower than the formulation most
      commonly dispensed by pharmacies.

PMID- 23144165
TI  - Future-proofing our community for natural disaster requires more attention on
      men.

PMID- 23144166
TI  - Peroxisome proliferator-activated receptor alpha expression changes in human
      pregnant myometrium.
AB  - Peroxisome proliferator-activated receptor alpha (PPARalpha) has been
      demonstrated to exhibit anti-inflammatory activities that are hypothesized to
      play a key role in labor suppression and maintenance of uterine quiescence. The
      aim of this study was to identify pregnancy- and labor-associated changes in
      PPARalpha in human myometrium. For this investigation, human myometrium was
      obtained from premenopausal women, and the study participants were categorized
      into the following 4 groups: nonpregnant (NP; n = 10), preterm not in labor (PNL;
      n = 10, gestation range 20-35 weeks), term not in labor (TNL; n = 20, gestation
      range 37-41 weeks), and term in labor (TL; n = 20, gestation range 37-41 weeks).
      Immunohistochemistry was used to locate and confirm the expression of PPARalpha.
      Relative quantitative real-time polymerase chain reaction (PCR) and Western
      blotting were employed to study the expression of anti-inflammatory PPARalpha and
      proinflammatory interleukin 1beta (IL-1beta). Immunohistochemistry indicated that
      PPARalpha was located in the nucleus of uterine smooth muscle cells. Compared to
      other groups, in PNL group, the PPARalpha messenger RNA (mRNA) and protein
      increased significantly. Decreased PPARalpha mRNA and protein expressions in
      myometrium were associated with labor while IL-1beta increased remarkably. There
      were negative correlations between PPARalpha and IL-1beta on mRNA (r = -.765, P <
      .01) and protein (r = -.624, P < .01) levels analyzed using Pearson test. In
      conclusion, human pregnancy is associated with changes in expression of PPARalpha
      and IL-1beta in myometrium. The changes observed suggest that PPARalpha may play
      a role in maintaining pregnancy or initiating labor through inhibiting the
      expression of IL-1beta in human myometrium.

PMID- 23144167
TI  - Bamboo shoots after the rain: development and challenges of autism intervention
      in China.
AB  - The purpose of this study was to gain an in-depth understanding of autism
      intervention in China, including history, progress, and current challenges. This
      qualitative research study included interviews with experienced professionals and
      observation at autism intervention organizations. Analysis of this empirical data
      led to three themes regarding this field. First, the development of the field can
      be described using the Chinese expression, mozhe shitou guohe (feeling stones to
      cross the river). Owing to limited exposure to outside information, methods are
      often created independent of research-based best practices. Second, autism
      intervention in China has had a strong, and until recently, almost exclusive,
      focus on young children. Finally, there are continued challenges to providing
      effective services that relate to the desires of parents and professionals to
      provide 'more'; a focus on quantity may be preventing a focus on quality. The
      article concludes with an analysis of the findings and practical implications
      that may be used by practitioners or scholars planning to do work in China.

PMID- 23144168
TI  - An exploration of crossover sexual offending.
AB  - Studies have produced equivocal findings regarding whether sex offenders are
      stable in their choice of victims. Indeed, it remains unclear whether a sex
      offender's subsequent victims are typically of the same gender, age range, and
      victim-perpetrator relationship as that of the initial victim. Although some
      differences may be attributed to methodological disparities, others are not. This
      study sought to clarify this question by examining the tendency of sex offenders
      to switch from one type of victim to another, both within an index offense and
      across offenses and all victims. Archival records of 789 incarcerated sex
      offenders were examined. Of those offenders who had multiple victims at the index
      offense (n = 279), 13% had victims of both genders, 14% had victims in different
      age categories (child, adolescent, and adult), and 13% had varying relationships
      with the victims (i.e., family member, acquaintance, or stranger). When the
      records of those with past sexual convictions were examined (n = 208), 20% of
      offenders had a prior victim of a different gender; 40% crossed over across age
      categories, and 48% of the repeat offenders had varying relationships with the
      victim across convictions. Offenders who had both male and female victims and
      offenders who had victims of varied relationship status across crimes had higher
      Static-99 risk scores than offenders who were more stable with regard to victim
      selection. These findings are compared to those of previous studies, focusing on
      how these results add clarity to a previous literature whose conclusions were
      challenged by the use of disparate sampling and research methodologies. 

PMID- 23144169
TI  - Macrophage microvesicles induce macrophage differentiation and miR-223 transfer.
AB  - Microvesicles are small membrane-bound particles comprised of exosomes and
      various-sized extracellular vesicles. These are released by several cell types.
      Microvesicles have a variety of cellular functions from communication to
      mediating growth and differentiation. Microvesicles contain proteins and nucleic
      acids. Previously, we showed that plasma microvesicles contain microRNAs
      (miRNAs). Based on our previous report, the majority of peripheral blood
      microvesicles are derived from platelets, while mononuclear phagocytes, including
      macrophages, are the second most abundant population. Here, we characterized
      macrophage-derived microvesicles and explored their role in the differentiation
      of naive monocytes. We also identified the miRNA content of the macrophage
      derived microvesicles. We found that RNA molecules contained in the macrophage
      derived microvesicles were transported to target cells, including mono cytes,
      endothelial cells, epithelial cells, and fibroblasts. Furthermore, we found that
      miR-223 was transported to target cells and was functionally active. Based on our
      observations, we hypothesize that microvesicles bind to and activate target
      cells. Furthermore, we find that microvesicles induce the differentiation of
      macrophages. Thus, defining key components of this response may identify novel
      targets to regulate host defense and inflammation.

PMID- 23144170
TI  - TLR4- and TRIF-dependent stimulation of B lymphocytes by peptide liposomes
      enables T cell-independent isotype switch in mice.
AB  - Immunoglobulin class switching from IgM to IgG in response to peptides is
      generally T cell-dependent and vaccination in T cell-deficient individuals is
      inefficient. We show that a vaccine consisting of a dense array of peptides on
      liposomes induced peptide-specific IgG responses totally independent of T-cell
      help. Independency was confirmed in mice lacking T cells and in mice deficient
      for MHC class II, CD40L, and CD28. The IgG titers were high, long-lived, and
      comparable with titers obtained in wild-type animals, and the antibody response
      was associated with germinal center formation, expression of activation-induced
      cytidine deaminase, and affinity maturation. The T cell-independent (TI) IgG
      response was strictly dependent on ligation of TLR4 receptors on B cells, and
      concomitant TLR4 and cognate B-cell receptor stimulation was required on a single
      cell level. Surprisingly, the IgG class switch was mediated by TIR-domain
      containing adapter inducing interferon-beta (TRIF), but not by MyD88. This study
      demonstrates that peptides can induce TI isotype switching when antigen and TLR
      ligand are assembled and appropriately presented directly to B lymphocytes. A TI
      vaccine could enable efficient prophylactic and therapeutic vaccination of
      patients with T-cell deficiencies and find application in diseases where
      induction of T-cell responses contraindicates vaccination, for example, in
      Alzheimer disease.

PMID- 23144171
TI  - Antibacterial effect of microvesicles released from human neutrophilic
      granulocytes.
AB  - Cell-derived vesicles represent a recently discovered mechanism for intercellular
      communication. We investigated their potential role in interaction of microbes
      with host organisms. We provide evidence that different stimuli induced isolated
      neutrophilic granulocytes to release microvesicles with different biologic
      properties. Only opsonized particles initiated the formation of microvesicles
      that were able to impair bacterial growth. The antibacterial effect of neutrophil
      derived microvesicles was independent of production of toxic oxygen metabolites
      and opsonization or engulfment of the microbes, but depended on beta(2) integrin
      function, continuous actin remodeling, and on the glucose supply. Neutrophil
      derived microvesicles were detected in the serum of healthy donors, and their
      number was significantly increased in the serum of bacteremic patients. We
      propose a new extracellular mechanism to restrict bacterial growth and
      dissemination.

PMID- 23144172
TI  - AngiomiR-126 expression and secretion from circulating CD34(+) and CD14(+) PBMCs:
      role for proangiogenic effects and alterations in type 2 diabetics.
AB  - Several peripheral blood mononuclear cell (PBMC)-derived cell populations can
      promote angiogenesis, and differences in CD34(+) or CD14(+) surface expression
      have been used to separate PBMC subpopulations in this respect. AngiomiRs,
      microRNAs regulating angiogenesis, are key regulators of angiogenic processes.
      The present study examines differential angiomiR expression/secretion from
      CD34(+)/CD14(+), CD34(+)/CD14(-), CD34(-)/CD14(+), and CD34(-)/CD14(-) PBMC
      subsets and their relevance for different proangiogenic properties. Notably, both
      circulating human CD34(+)/14(+) and CD34(+)/14(-) PBMC subsets and their
      supernatants exerted more potent proangiogenic effects compared with CD34(-) PBMC
      subsets. MiR-126 was identified as most differentially expressed angiomiR in
      CD34(+) compared with CD34(-) PBMC subsets, determined by miR-array and RT-PCR
      validation. Modulation of miR-126 by anti-miR-126 or miR-mimic-126 treatment
      resulted in significant loss or increase of proangiogenic effects of CD34(+)
      PBMCs. MiR-126 levels in supernatants of CD34(+) PBMC subsets were substantially
      higher compared with CD34(-) PBMC subsets. MiR-126 was secreted in
      microvesicles/exosomes, and inhibition of their release impaired CD34(+) PBMCs
      proangiogenic effects. Notably, high-glucose treatment or diabetes reduced miR
      126 levels of CD34(+) PBMCs, associated with impaired proangiogenic properties
      that could be rescued by miR-mimic-126 treatment. The present findings provide a
      novel molecular mechanism underlying increased proangiogenic effects of CD34(+)
      PBMCs, that is, angiomiR-126 expression/secretion. Moreover, an alteration of
      angiomiR-126 expression in CD34(+) PBMCs in diabetes provides a novel pathway
      causing impaired proangiogenic effects.

PMID- 23144173
TI  - Immediate and subsequent effects of matched and unmatched stimuli on targeted
      vocal stereotypy and untargeted motor stereotypy.
AB  - The authors evaluated the effects of matched and unmatched stimuli on immediate
      and subsequent engagement in targeted vocal stereotypy (Experiment 1) and
      untargeted motor stereotypy (Experiment 2). Results of Experiment 1 showed that
      (a) matched stimulation decreased immediate engagement in vocal stereotypy for 8
      of 11 participants and increased subsequent engagement in vocal stereotypy for
      only 1 of the 8 participants and (b) unmatched stimulation decreased immediate
      engagement in vocal stereotypy for only 1 of 10 participants and did not increase
      subsequent engagement in vocal stereotypy for this participant. Results of
      Experiment 2 showed that for 8 of 14 participants, untargeted stereotypy
      increased when the matched or unmatched stimulus was present, after it was
      removed, or both. The authors briefly discuss the potential clinical implications
      of using matched stimulation to decrease vocal stereotypy and limitations of the
      findings.

PMID- 23144174
TI  - The effect of varying teacher presentation rates on responding during discrete
      trial training for two children with autism.
AB  - Recent research has emphasized the importance of manipulating antecedent
      variables to reduce interfering behaviors when teaching persons with autism. Few
      studies have focused on the effects of the rate of teacher-presented
      instructional demands as an independent variable. In this study, an alternating
      treatment design was used to evaluate the effects of varied rates of teacher
      presented demands (1 s, 5 s, 10 s) on the occurrence of problem behavior,
      opportunities to respond, responses emitted, accuracy of responding, and
      magnitude and rate of reinforcement for two children with autism. Results
      indicated that fast presentation rate (1 s) resulted in lower rates of problem
      behavior, higher frequencies of instructional demands, higher frequencies of
      participant responding, and greater magnitudes and rates of reinforcement.
      Differential effects on accuracy of responding across conditions were not
      observed. Implications for manipulating the rate of teacher-presented
      instructional demands as an antecedent variable to reduce problem behavior are
      discussed.

PMID- 23144175
TI  - Bipolar disorder in pregnancy: to treat or not to treat?

PMID- 23144176
TI  - Case fatality rate in pulmonary embolism according to age and stability.
AB  - Data from the Nationwide Inpatient Sample, 1999 to 2008, were used to assess the
      effects of advancing age on in-hospital case fatality rate of patients with acute
      pulmonary embolism (PE) stratified according to stability. Among adults, all
      cause case fatality was affected more by advancing age (1.8 deaths/10 years of
      age) than death attributable to PE (0.7 deaths/10 years of age). All-cause case
      fatality rate was affected more by advancing age in unstable adults than in
      stable adults (5.3 deaths/10 years of age vs 1.7 deaths/10 years of age). Case
      fatality rate attributable to PE was also affected more by advancing age in
      unstable adults than in stable adults (4.1 deaths/10 years of age vs 0.6
      deaths/10 years of age). Limited data suggest that the case fatality rate of
      children was comparable to that of the elderly individuals. These results may
      influence the prognostic value of risk assessment tools for patients with PE. 

PMID- 23144177
TI  - Predictive value of neutrophil to lymphocyte ratio in clinical outcomes of non-ST
      elevation myocardial infarction and unstable angina pectoris: a 3-year follow-up.
AB  - We sought to determine the prognostic value of neutrophil to lymphocyte ratio
      (NLR) in non-ST elevation myocardial infarction (NSTEMI) and unstable angina
      pectoris (UAP). A total of 308 (mean age 59.22 +/- 11.93) patients with NSTEMI
      and UAP were prospectively evaluated. The study population was divided into
      tertiles based on admission NLR values. The patients were followed for clinical
      outcomes for up to 3 years after discharge. In the Kaplan-Meier survival
      analysis, 3-year mortality was 21.6% in patients with high NLR versus 3% in the
      low-NLR group (P < .001). In a receiver-operating characteristic curve analysis,
      an NLR value of 3.04 was identified as an effective cut point in NSTEMI and UAP
      of a 3-year cardiovascular mortality (area under curve [AUC] = 0.86, 95%
      confidence interval [CI] 0.8-0.92). An NLR value >3.04 yielded a sensitivity of
      79% and specificity of 71%. Admission NLR is the strong and independent predictor
      of a 3-year cardiovascular mortality in patients with NSTEMI and UAP. 

PMID- 23144178
TI  - Prognostic value of red cell distribution width in patients with pulmonary
      embolism.
AB  - Elevated red blood cell distribution width (RDW) has been associated with adverse
      outcomes of heart failure and pulmonary hypertension. A total of 702 consecutive
      patients with acute pulmonary embolism (PE) were evaluated. There was a graded
      increase in mortality rate with RDW quartiles of 5.8% in quartile I (<=13.6),
      9.7% in quartile II (13.7%-14.5%), 13.1% in quartile III (14.6%-16.3%), and 20%
      in quartile IV (>16.3%; P < .001). Patients who died had higher baseline RDW
      values (16.1% [11.7-28.3] vs 14.5% [10.7-32.5]; P < .001). The optimal cutoff
      value of RDW for predicting in-hospital mortality was >=15%. The area under the
      curve of mortality for RDW was 0.649 (confidence interval [CI]: 0.584-0.715); the
      negative predictive value was 93%. In multivariable regression analysis, RDW
      remained associated with an increased odds of death (odds ratio: 1.2, 95% CI: 1.1
      1.4). High RDW level was an independent predictor of short-term mortality in PE.
      The RDW levels may provide a potential marker to predict outcome in patients with
      PE. 

PMID- 23144179
TI  - Management of patients with spontaneous intracranial hypotension causing altered
      level of consciousness: report of two cases and review of literature.
AB  - BACKGROUND: Decreased level of consciousness is a rare neurological manifestation
      of spontaneous intracranial hypotension (SIH), which typically presents with
      orthostatic headache. The optimal management of this uncommon presentation
      remains uncertain. METHODS: We analyzed the presentation, management and outcome
      of two patients in our institution and reviewed 22 patients reported in the
      literature with SIH and decreased level of consciousness, defined as any decrease
      in the patient's Glasgow Coma Scale score. RESULTS: There were 20 male and four
      female patients (M:F ratio of 5:1) with an average age of 52 years (range 37 to
      68 years). There was a variable time interval of up to many months between the
      initial presentation of SIH and changes in the level of consciousness. An
      epidural autologous blood patch was eventually successful in 79% of the patients,
      although up to three trials were necessary in seven of these patients.
      Intrathecal saline infusion used as a temporizing measure resulted in excellent
      response within hours in five out of six patients who received this treatment.
      Drainage of the subdural collection either did not result in any sustained
      improvement or resulted in clinical deterioration in 12 out of 12 patients who
      received this treatment. CONCLUSIONS: In the absence of a clinical trial because
      of the rarity of this entity, the treatment of SIH complicated by decreased level
      of consciousness remained controversial in the past. However, current collective
      experience supports early treatment of patients with SIH and decreased level of
      consciousness with one or more epidural blood patches. Fibrin glue and surgical
      duroplasty are the next steps in the management of patients in whom epidural
      blood patches fail. Drainage of the subdural collections may be detrimental.

PMID- 23144180
TI  - Medication-overuse headache and opioid-induced hyperalgesia: A review of
      mechanisms, a neuroimmune hypothesis and a novel approach to treatment.
AB  - INTRODUCTION: Patients with chronic headache who consume large amounts of
      analgesics are often encountered in clinical practice. Excessive intake of
      analgesics is now considered to be a cause, rather than simply a consequence, of
      frequent headaches, and as such the diagnosis "medication-overuse headache" (MOH)
      has been formulated. Despite the prevalence and clinical impact of MOH, the
      pathophysiology behind this disorder remains unclear and specific mechanism-based
      treatment options are lacking. DISCUSSION: Although most acute headache
      treatments have been alleged to cause MOH, here we conclude from the literature
      that opioids are a particularly problematic drug class consistently associated
      with worsening headache. MOH may not be a single entity, as each class of drug
      implicated may cause MOH via a different mechanism. Recent evidence indicates
      that chronic opioid administration may exacerbate pain in the long term by
      activating toll-like receptor-4 on glial cells, resulting in a pro-inflammatory
      state that manifests clinically as increased pain. Thus, from the available
      evidence it seems opioid-overuse headache is a phenomenon similar to opioid
      induced hyperalgesia, which derives from a cumulative interaction between central
      sensitisation, due to repeated activation of nociceptive pathways by recurrent
      headaches, and pain facilitation due to glial activation. CONCLUSION: Treatment
      strategies directed at inhibiting glial activation may be of benefit alongside
      medication withdrawal in the management of MOH.

PMID- 23144181
TI  - Reevaluation of the reliability and usefulness of the somatic homologous
      recombination reporter lines.
AB  - A widely used approach for assessing genome instability in plants makes use of
      somatic homologous recombination (SHR) reporter lines. Here, we review the
      published characteristics and uses of SHR lines. We found a lack of detailed
      information on these lines and a lack of sufficient evidence that they report
      only homologous recombination. We postulate that instead of SHR, these lines
      might be reporting a number of alternative stress-induced stochastic events known
      to occur at transcriptional, posttranscriptional, and posttranslational levels.
      We conclude that the reliability and usefulness of the somatic homologous
      recombination reporter lines requires revision. Thus, more detailed information
      about these reporter lines is needed before they can be used with confidence to
      measure genome instability, including the complete sequences of SHR constructs,
      the genomic location of reporter genes and, importantly, molecular evidence that
      reconstituted gene expression in these lines is indeed a result of somatic
      recombination.

PMID- 23144182
TI  - In planta somatic homologous recombination assay revisited: a successful and
      versatile, but delicate tool.
AB  - Marker-transgene-dependent lines of Arabidopsis thaliana measuring somatic
      homologous recombination (SHR) have been available for almost two decades. Here
      we discuss mechanisms of marker-gene restoration, comment on results obtained
      using the reporter lines, and stress how caution must be applied to avoid
      experimental problems or false interpretation in the use of SHR reporter lines.
      Although theoretically possible, we conclude that explanations other than SHR are
      unlikely to account for restoration of marker gene expression in the SHR lines
      when used with appropriate controls. We provide an overview of some of the most
      important achievements obtained with the SHR lines, give our view of the
      limitations of the system, and supply the reader with suggestions on the proper
      handling of the SHR lines. We are convinced that SHR lines are and will remain in
      the near future a valuable tool to explore the mechanism and influence of
      external and internal factors on genome stability and DNA repair in plants.

PMID- 23144185
TI  - The circadian clock-associated small GTPase LIGHT INSENSITIVE PERIOD1 suppresses
      light-controlled endoreplication and affects tolerance to salt stress in
      Arabidopsis.
AB  - Circadian clocks are biochemical timers regulating many physiological and
      molecular processes according to the day/night cycle. The small GTPase LIGHT
      INSENSITIVE PERIOD1 (LIP1) is a circadian clock-associated protein that regulates
      light input to the clock. In the absence of LIP1, the effect of light on free
      running period length is much reduced. Here, we show that in addition to
      suppressing red and blue light-mediated photomorphogenesis, LIP1 is also required
      for light-controlled inhibition of endoreplication and tolerance to salt stress
      in Arabidopsis (Arabidopsis thaliana). We demonstrate that in the processes of
      endoreplication and photomorphogenesis, LIP1 acts downstream of the red and blue
      light photoreceptors phytochrome B and cryptochromes. Manipulation of the
      subcellular distribution of LIP1 revealed that the circadian function of LIP1
      requires nuclear localization of the protein. Our data collectively suggest that
      LIP1 influences several signaling cascades and that its role in the entrainment
      of the circadian clock is independent from the other pleiotropic effects. Since
      these functions of LIP1 are important for the early stages of development or
      under conditions normally experienced by germinating seedlings, we suggest that
      LIP1 is a regulator of seedling establishment.

PMID- 23144183
TI  - Cysteine-generated sulfide in the cytosol negatively regulates autophagy and
      modulates the transcriptional profile in Arabidopsis.
AB  - In Arabidopsis thaliana, DES1 is the only identified L-Cysteine desulfhydrase
      located in the cytosol, and it is involved in the degradation of cysteine and the
      concomitant production of H(2)S in this cell compartment. Detailed
      characterization of the T-DNA insertion mutants des1-1 and des1-2 has provided
      insight into the role of sulfide metabolically generated in the cytosol as a
      signaling molecule. Mutations of L-CYS DESULFHYDRASE 1 (DES1) impede H(2)S
      generation in the Arabidopsis cytosol and strongly affect plant metabolism.
      Senescence-associated vacuoles are detected in mesophyll protoplasts of des1
      mutants. Additionally, DES1 deficiency promotes the accumulation and lipidation
      of the ATG8 protein, which is associated with the process of autophagy. The
      transcriptional profile of the des1-1 mutant corresponds to its premature
      senescence and autophagy-induction phenotypes, and restoring H(2)S generation has
      been shown to eliminate the phenotypic defects of des1 mutants. Moreover, sulfide
      is able to reverse ATG8 accumulation and lipidation, even in wild-type plants
      when autophagy is induced by carbon starvation, suggesting a general effect of
      sulfide on autophagy regulation that is unrelated to sulfur or nitrogen
      limitation stress. Our results suggest that cysteine-generated sulfide in the
      cytosol negatively regulates autophagy and modulates the transcriptional profile
      of Arabidopsis.

PMID- 23144186
TI  - Deficiency in a very-long-chain fatty acid beta-ketoacyl-coenzyme a synthase of
      tomato impairs microgametogenesis and causes floral organ fusion.
AB  - Previously, it was shown that beta-ketoacyl-coenzyme A synthase ECERIFERUM6
      (CER6) is necessary for the biosynthesis of very-long-chain fatty acids with
      chain lengths beyond C28 in tomato (Solanum lycopersicum) fruits and C26 in
      Arabidopsis (Arabidopsis thaliana) leaves and the pollen coat. CER6 loss of
      function in Arabidopsis resulted in conditional male sterility, since pollen coat
      lipids are responsible for contact-mediated pollen hydration. In tomato, on the
      contrary, pollen hydration does not rely on pollen coat lipids. Nevertheless,
      mutation in SlCER6 impairs fertility and floral morphology. Here, the
      contribution of SlCER6 to the sexual reproduction and flower development of
      tomato was addressed. Cytological analysis and cross-pollination experiments
      revealed that the slcer6 mutant has male sterility caused by (1) hampered pollen
      dispersal and (2) abnormal tapetum development. SlCER6 loss of function provokes
      a decrease of n- and iso-alkanes with chain lengths of C27 or greater and of
      anteiso-alkanes with chain lengths of C28 or greater in flower cuticular waxes,
      but it has no impact on flower cuticle ultrastructure and cutin content.
      Expression analysis confirmed high transcription levels of SlCER6 in the anther
      and the petal, preferentially in sites subject to epidermal fusion. Hence, wax
      deficiency was proposed to be the primary reason for the flower fusion phenomenon
      in tomato. The SlCER6 substrate specificity was revisited. It might be involved
      in elongation of not only linear but also branched very-long-chain fatty acids,
      leading to production of the corresponding alkanes. SlCER6 implements a function
      in the sexual reproduction of tomato that is different from the one in
      Arabidopsis: SlCER6 is essential for the regulation of timely tapetum degradation
      and, consequently, microgametogenesis.

PMID- 23144187
TI  - Loss of function of Arabidopsis C-terminal domain phosphatase-like1 activates
      iron deficiency responses at the transcriptional level.
AB  - The expression of genes that control iron (Fe) uptake and distribution (i.e. Fe
      utilization-related genes) is tightly regulated. Fe deficiency strongly induces
      Fe utilization-related gene expression; however, little is known about the
      mechanisms that regulate this response in plants. Transcriptome analysis of an
      Arabidopsis (Arabidopsis thaliana) mutant defective in RNA polymerase II C
      terminal domain-phosphatase-like1 (CPL1) revealed significant up-regulation of Fe
      utilization-related genes (e.g. IRON-REGULATED TRANSPORTER1), suggesting the
      importance of RNA metabolism in Fe signaling. An analysis using multiple cpl1
      alleles established that cpl1 mutations enhanced specific transcriptional
      responses to low Fe availability. Changes in protein level were less prominent
      than those in transcript level, indicating that cpl1-2 mainly affects the Fe
      deficiency response at the transcriptional level. However, Fe content was
      significantly increased in the roots and decreased in the shoots of cpl1-2
      plants, indicating that the cpl1 mutations do indeed affect Fe homeostasis.
      Furthermore, root growth of cpl1-2 showed improved tolerance to Fe deficiency and
      cadmium (Cd) toxicity. cpl1-2 plants accumulated more Cd in the shoots,
      suggesting that Cd toxicity in the roots of this mutant is averted by the
      transport of excess Cd to the shoots. Genetic data indicate that cpl1-2 likely
      activates Fe deficiency responses upstream of both FE-DEFICIENCY-INDUCED
      TRANSCRIPTION FACTOR-dependent and -independent signaling pathways.
      Interestingly, various osmotic stress/abscisic acid (ABA)-inducible genes were up
      regulated in cpl1-2, and the expression of some ABA-inducible genes was
      controlled by Fe availability. We propose that the cpl1 mutations enhance Fe
      deficiency signaling and promote cross talk with a branch of the osmotic
      stress/ABA signaling pathway.

PMID- 23144188
TI  - A conifer ABI3-interacting protein plays important roles during key transitions
      of the plant life cycle.
AB  - ABI3 (for ABSCISIC ACID INSENSITIVE3), a transcription factor of the abscisic
      acid signal transduction pathway, plays a major role during seed development,
      dormancy inception, and dormancy maintenance. This protein appears to also
      function in meristematic and vegetative plant tissues and under certain stress
      conditions. We have isolated the ABI3 gene ortholog (CnABI3) from yellow cedar
      (Callitropsis nootkatensis) and found that it was functionally similar to other
      ABI3 genes of angiosperms. Here, we report that using a yeast (Saccharomyces
      cerevisiae) two-hybrid approach, we have identified another protein of yellow
      cedar (CnAIP2; for CnABI3 INTERACTING PROTEIN2) that physically interacts with
      CnABI3. Functional analyses revealed that CnAIP2 plays important roles during key
      transitions in the plant life cycle: (1) CnAIP2 impaired seed development and
      reduced seed dormancy; (2) CnAIP2 promoted root development, particularly the
      initiation of lateral roots, and the CnAIP2 gene promoter was exquisitely auxin
      sensitive; and (3) CnAIP2 promoted the transition from vegetative growth to
      reproductive initiation (i.e. flowering). The nature of the effects of CnAIP2 on
      these processes and other evidence place CnAIP2 in the category of a "global"
      regulator, whose actions are antagonistic to those of ABI3.

PMID- 23144189
TI  - Identification and origin of N-linked beta-D-N-acetylglucosamine monosaccharide
      modifications on Arabidopsis proteins.
AB  - Many plant proteins are modified with N-linked oligosaccharides at asparagine-X
      serine/threonine sites during transit through the endoplasmic reticulum and the
      Golgi. We have identified a number of Arabidopsis (Arabidopsis thaliana) proteins
      with modifications consisting of an N-linked N-acetyl-D-glucosamine
      monosaccharide (N-GlcNAc). Electron transfer dissociation mass spectrometry
      analysis of peptides bearing this modification mapped the modification to
      asparagine-X-serine/threonine sites on proteins that are predicted to transit
      through the endoplasmic reticulum and Golgi. A mass labeling method was developed
      and used to study N-GlcNAc modification of two thioglucoside glucohydrolases
      (myrosinases), TGG1 and TGG2 (for thioglucoside glucohydrolase). These
      myrosinases are also modified with high-mannose (Man)-type glycans. We found that
      N-GlcNAc and high-Man-type glycans can occur at the same site. It has been
      hypothesized that N-GlcNAc modifications are generated when endo-beta-N
      acetylglucosaminidase (ENGase) cleaves N-linked glycans. We examined the effects
      of mutations affecting the two known Arabidopsis ENGases on N-GlcNAc modification
      of myrosinase and found that modification of TGG2 was greatly reduced in one of
      the single mutants and absent in the double mutant. Surprisingly, N-GlcNAc
      modification of TGG1 was not affected in any of the mutants. These data support
      the hypothesis that ENGases hydrolyze high-Man glycans to produce some of the N
      GlcNAc modifications but also suggest that some N-GlcNAc modifications are
      generated by another mechanism. Since N-GlcNAc modification was detected at only
      one site on each myrosinase, the production of the N-GlcNAc modification may be
      regulated.

PMID- 23144191
TI  - Salivary alpha-amylase and intended harsh caregiving in response to infant
      crying: evidence for physiological hyperreactivity.
AB  - This is the first study on adults' physiological reactivity to infant cry sounds
      and the association with intended harsh parenting using salivary alpha-amylase
      (sAA) as a novel and noninvasive marker of autonomic nervous system activity. The
      sample consisted of 184 adult twin pairs. In an experimental design, cry sounds
      were presented and adults' perception and their intended caregiving responses
      were measured. Saliva samples were collected after each cry sound. For the
      majority of the sample, a decrease in sAA across the cry paradigm was observed.
      However, adults who indicated that they would respond in a harsh way to the
      crying infant were significantly less likely to show a decrease in sAA.
      Consistent with previous studies on physiological hyperreactivity in abusive
      parents, these findings suggest that failure to habituate to repeated infant
      crying may be one of the mediating mechanisms through which excessive,
      inconsolable, and high-pitched infant crying triggers less optimal caregiving.

PMID- 23144192
TI  - Treatment and outcomes for chronic myelomonocytic leukemia compared to
      myelodysplastic syndromes in older adults.
AB  - Prior studies have investigated patients' characteristics, treatments, and
      outcomes for older adults with myelodysplastic syndromes, but most failed to
      distinguish chronic myelomonocytic leukemia. Recognizing potentially important
      differences between the diseases, we undertook a population-based comparison of
      baseline characteristics, treatments, and outcomes between older adults with
      chronic myelomonocytic leukemia and myelodysplastic syndromes. The patients' data
      were obtained from Surveillance Epidemiology and End Results registry data from
      2001-2005, linked to Medicare claims. Baseline characteristics, treatment (red
      blood cell transfusions, hematopoietic growth factors, hypomethylating agents,
      chemotherapy or transplantation), progression to acute myeloid leukemia, and
      overall survival were compared using bivariate techniques. Multivariate logistic
      regression estimated differences in treatments received. Cox proportional hazard
      models estimated the effects of chronic myelomonocytic leukemia relative to
      myelodysplastic syndromes on progression-free survival. A larger proportion of
      patients with chronic myelomonocytic leukemia (n=792), compared to patients with
      myelodysplastic syndromes (n=7,385), failed to receive any treatment (25% versus
      15%; P<0.0001), or only received red blood cell transfusions (19.8% versus 16.7%;
      P=0.037). A larger percentage of patients with chronic myelomonocytic leukemia
      progressed to acute myeloid leukemia (42.6% versus 15.5%, respectively;
      P<0.0001), with shorter time to progression. Chronic myelomonocytic leukemia
      patients had a shorter median survival (13.3 versus 23.3 months; P<0.0001) and
      lower 3-year survival rate (19% versus 36%; P<0.0001). Adjusted estimates,
      controlling for baseline characteristics and selected treatments, indicate that
      chronic myelomonocytic leukemia was associated with an increased risk of
      progression to acute myeloid leukemia or death (HR 2.22; P<0.0001), compared to
      myelodysplastic syndromes. In conclusion, chronic myelomonocytic leukemia is less
      frequently treated in older adults and is associated with worse outcomes, even
      after controlling for the patients' baseline characteristics and selected
      treatments. Our data suggest the need for continued evaluation of the biological
      differences between these diseases and clinical trials targeting chronic
      myelomonocytic leukemia.

PMID- 23144193
TI  - Everolimus in combination with rituximab induces complete responses in heavily
      pretreated diffuse large B-cell lymphoma.
AB  - Diffuse large B-cell lymphoma is an aggressive non-Hodgkin's lymphoma without a
      standard therapy for patients who relapse after or are not eligible for salvage
      autologous stem cell transplantation. In vitro analysis of lymphoma cell lines
      has shown that everolimus can inhibit cell cycle progression in vitro and
      inhibitors of the mammalian target of rapamycin have already demonstrated single
      agent activity in relapsed non-Hodgkin's lymphomas including diffuse large B-cell
      lymphoma, validating mammalian target of rapamycin as a viable therapeutic
      target. We performed an open label phase II study of everolimus, an inhibitor of
      mammalian target of rapamycin, in combination with rituximab to examine efficacy
      and tolerability in patients with relapsed/refractory diffuse large B-cell
      lymphoma. Eligible patients were treated with everolimus 10 mg by mouth once
      daily on days 1-28 of a 28-day cycle with rituximab administered weekly during
      cycle one and then on day one of subsequent cycles. Patients were treated for a
      total of 12 cycles or until disease progression. The primary end-point was
      objective response rate, with secondary end-points being toxicity, progression
      free survival, duration of response, and overall survival. Twenty-six patients
      (24 evaluable) were enrolled and had an overall response rate of 38% [90% CI (21%
      56%)] with three complete responses and six partial responses among these 24
      patients. The median duration of response among responders was 8.1 months. At a
      median follow-up of 12 months, the overall survival rate was 37% [90% CI (20%
      54%)]. The most common grade 3 to 4 toxicities were neutropenia, anemia, and
      thrombocytopenia. In conclusion, everolimus in combination with rituximab is well
      tolerated and demonstrates activity in relapsed diffuse large B-cell lymphoma.
      Further studies of this combination are warranted.

PMID- 23144194
TI  - Association between B-cell receptor responsiveness and disease progression in B
      cell chronic lymphocytic leukemia: results from single cell network profiling
      studies.
AB  - While many prognostic markers in B-cell chronic lymphocytic leukemia provide
      insight into the biology of the disease, few have been demonstrated to be useful
      in the daily management of patients. B-cell receptor signaling is a driving event
      in the progression of B-cell chronic lymphocytic leukemia and markers of B-cell
      receptor responsiveness have been shown to be of prognostic value. Single cell
      network profiling, a multiparametric flow cytometry-based assay, allows
      functional signaling analysis at the level of the single cell. B-cell receptor
      signaling proteins (i.e. p-SYK, p-NF-kappaB p65, p-ERK, p-p38, p-JNK) were
      functionally characterized by single cell network profiling in samples from
      patients with B-cell chronic lymphocytic leukemia in an exploratory study (n=27)
      after stimulation with anti-IgM. Significant associations of single cell network
      profiling data with clinical outcome (i.e. time to first treatment), as assessed
      by Cox regression models, were then confirmed in patients' samples in two other
      sequential independent studies, i.e. test study 1 (n=30), and test study 2
      (n=37). In the exploratory study, higher responsiveness of the B-cell receptor
      signaling proteins to anti-IgM was associated with poor clinical outcomes.
      Patients' clustering based on signaling response was at least as powerful in
      discriminating different disease courses as traditional prognostic markers. In an
      unselected subgroup of patients with Binet stage A disease (n=21), increased anti
      IgM-modulated p-ERK signaling was shown to be a significant, independent
      predictor of shorter time to first treatment. This result was independently
      confirmed in two test cohorts from distinct populations of patients. In
      conclusion, these findings support the utility of the single cell network
      profiling assay in elucidating signaling perturbations with the potential for the
      development of a clinically useful prognostic test in patients with early stage B
      cell chronic lymphocytic leukemia. These data support the clinical relevance of B
      cell receptor signaling in B-cell chronic lymphocytic leukemia, and suggest a key
      role of ERK activation in the physiopathology of this leukemia.

PMID- 23144195
TI  - Splenectomy as a curative treatment for immune thrombocytopenia: a retrospective
      analysis of 233 patients with a minimum follow up of 10 years.
AB  - The treatment of choice in steroid-resistant immune thrombocytopenia is still
      controversial due to the recent advent of new drugs (anti-CD20 antibodies and
      thrombopoietin mimetics) that have encouraged a generalized tendency to delay
      splenectomy. Consequently, it is extremely importance to define the efficacy and
      safety of splenectomy in the long term. We retrospectively analyzed the data of
      233 patients affected by immune thrombocytopenia who underwent splenectomy
      between 1959 and 2001 in 6 European hematologic institutions and who have now a
      minimum follow up of ten years from surgery. Of the 233 patients, 180 (77%)
      achieved a complete response and 26 (11%) a response. Sixty-eight of 206 (33%)
      responsive patients relapsed, mostly (75%) within four years from first response.
      In 92 patients (39.5%), further treatment was required after splenectomy that was
      effective in 76 cases (83%). In 138 patients (59%), response was maintained free
      of any treatment at last contact. No significant association between baseline
      characteristics and likelihood of stable response was found. Overall, 73 (31%)
      and 58 (25%) patients experienced at least one infectious or hemorrhagic
      complication, which was fatal in 2 and 3 patients, respectively. A stable
      response to splenectomy was associated with a lower rate of infections (P=0.004)
      and hemorrhages (P<0.0001). Thrombosis developed in 18 patients (8%) and was
      fatal in 4. Splenectomy achieved a long-term stable response in approximately 60%
      of cases. Complications mainly affected non-responding patients and were fatal in
      a minority.

PMID- 23144196
TI  - Central nervous system recurrence of systemic lymphoma in the era of stem cell
      transplantation--an International Primary Central Nervous System Lymphoma Study
      Group project.
AB  - Autologous stem cell transplantation has greatly improved the prognosis of
      systemic recurrent non-Hodgkin's lymphoma. However, no prospective data are
      available concerning the feasibility and efficacy of this strategy for systemic
      lymphoma relapsing in the central nervous system. We, therefore, we performed an
      international multicenter retrospective study of patients with a central nervous
      system recurrence of systemic lymphoma to assess the outcome of these patients in
      the era of stem cell transplantation. We collected clinical and treatment data on
      patients with a first central nervous system recurrence of systemic lymphoma
      treated between 2000 and 2010 in one of five centers in four countries. Patient-
      and treatment-related factors were analyzed and compared descriptively. Primary
      outcome measures were overall survival and percentage of patients transplanted.
      We identified 92 patients, with a median age of 59 years and a median Eastern
      Cooperative Oncology Group/World Health Organization performance status of 2, of
      whom 76% had diffuse large B-cell histology. The majority (79%) of these patients
      were treated with systemic chemotherapy with or without intravenous rituximab.
      Twenty-seven patients (29%) were transplanted; age and insufficient response to
      induction chemotherapy were the main reasons for not being transplanted in the
      remaining 65 patients. The median overall survival was 7 months (95% confidence
      interval 2.6-11.4), being 8 months (95% confidence interval 3.8-5.2) for patients
      <= 65 years old. The 1-year survival rate was 34.8%; of the 27 transplanted
      patients 62% survived more than 1 year. The Memorial Sloan Kettering Prognostic
      Index for primary central nervous system lymphoma was prognostic for both
      undergoing transplantation and survival. In conclusion, despite the availability
      of autologous stem cell transplantation for patients with central nervous system
      progression or relapse of systemic lymphoma, prognosis is still poor. Long-term
      survival is, however, possible and more likely in patients able to undergo stem
      cell transplantation.

PMID- 23144197
TI  - PML-RARalpha co-operates with Sox4 in acute myeloid leukemia development in mice.
AB  - Acute promyelocytic leukemia is characterized by a chromosomal translocation
      involving the retinoic acid receptor alpha gene. To identify co-operating
      pathways to leukemogenesis, we crossed MRP8-PML/RARA transgenic mice with BXH-2
      mice which harbor an endogenous murine leukemia virus that causes acute myeloid
      leukemia. Approximately half of the leukemias that arose in this cross showed
      features of acute promyelocytic leukemia. We identified 22 proviral insertion
      sites in acute promyelocytic-like leukemias and focused our analysis on insertion
      at Sox4, a HMG box transcription factor. Using a transplant model, co-operation
      between PML-RARalpha and Sox4 was confirmed with increased penetrance and reduced
      latency of disease. Interestingly, karyotypic analysis revealed cytogenetic
      changes suggesting that the factors combined to initiate but not complete
      leukemic transformation. The cooperation between these transcription factors is
      consistent with the paradigm of multiple routes to the disease and reinforces the
      concept that transcription factor networks are important therapeutic targets in
      myeloid leukemias.

PMID- 23144198
TI  - Lenalidomide as salvage treatment for multiple myeloma relapsing after allogeneic
      hematopoietic stem cell transplantation: a report from the French Society of Bone
      Marrow and Cellular Therapy.
AB  - Optimal salvage treatment for multiple myeloma relapsing after allogeneic stem
      cell transplantation remains to be determined. Usually, such patients have been
      heavily pre-treated and present at relapse with a relatively refractory disease.
      Immunomodulatory properties of lenalidomide may be beneficial by facilitating a
      graft-versus-myeloma effect after allogeneic stem cell transplantation. However,
      the safety of such treatment is still under debate. We conducted a multicenter
      retrospective study and included 52 myeloma patients receiving lenalidomide alone
      or in combination with dexamethasone as salvage therapy after allogeneic stem
      cell transplantation. The first aim was to assess the efficacy and tolerance of
      this drug. The second aim was to evaluate its potential immunomodulatory effects
      evaluated on the occurrence of acute graft-versus-host disease under treatment.
      In this cohort, we show that lenalidomide can induce a high response rate of 83%
      (including 29% complete response). On lenalidomide therapy, 16 patients (31%)
      developed or exacerbated an acute graft-versus-host disease, which was the only
      factor significantly associated with an improved anti-myeloma response. Side
      effects were mostly reversible, whereas 2 deaths (4%) could be attributed to
      treatment toxicity and to graft-versus-host disease, respectively. With a median
      follow up of 16.3 months, the median overall and progression free survival were
      30.5 and 18 months, respectively, independently of the occurrence of acute graft
      versus-host disease under lenalidomide. Lenalidomide can induce high response
      rates in myeloma relapsing after allogeneic stem cell transplantation at least in
      part by triggering an allogeneic anti-myeloma response. Induced graft-versus-host
      disease has to be balanced against the potential benefit in terms of disease
      control. Further immunological studies would help us understand lenalidomide
      immunomodulatory activity in vivo.

PMID- 23144199
TI  - H-Net, the European Network for Harmonization of Training in Hematology, and its
      policy.

PMID- 23144200
TI  - Melphalan, lenalidomide and dexamethasone for the treatment of immunoglobulin
      light chain amyloidosis: results of a phase II trial.
AB  - We report results of a phase II trial of combination of melphalan, lenalidomide,
      and dexamethasone for the treatment of immunoglobulin light chain (AL)
      amyloidosis. The primary objectives were tolerability and hematologic response
      rate; secondary objectives were organ responses and survival. Treatment protocol
      consisted of melphalan 5 mg/m(2)/day for four days, lenalidomide 10 mg/day for 21
      days and dexamethasone 20-40 mg once a week every 28 days for a total of 12
      cycles. Sixteen subjects were enrolled of whom 14 completed at least 3 cycles and
      were evaluable for response. Grade 3/4 toxicities were experienced by 88% (n=14),
      the most common being myelosuppression (n=7). Dose reductions occurred in 85%
      (n=12 of 14) of subjects. Hematologic partial and complete responses were
      achieved by 43% (n=6 of 14) and 7% (n=1 of 14), respectively. The median overall
      survival has not been reached and median progression-free survival is 24 months.
      In conclusion, this combination is associated with significant myelosuppression
      leading to dose modifications and producing minor hematologic responses in AL
      amyloidosis. http://clinicaltrials.gov/ct2/show/NCT00679367.

PMID- 23144201
TI  - Myeloablative chemotherapy for chemo-sensitive recurrent follicular lymphoma:
      potential benefit in second relapse.
AB  - Defining the role of high-dose therapy with autologous stem cell rescue in the
      therapeutic algorithm of follicular lymphoma remains a major challenge. In
      contrast to the acknowledged poor outcome associated with cyclophosphamide/total
      body irradiation conditioning in heavily pretreated patients, the prognostic
      impact of the number of previous therapy lines in patients treated with the
      chemotherapy-only containing regimen, BEAM, is unknown. From 1997 to 2008 80
      patients (41 males, 39 females; median age, 51 years; range, 31-67) received high
      dose therapy with autologous stem cell rescue with BEAM for relapsed follicular
      lymphoma at our center. Overall survival and time-to-progression were analyzed
      according to the number of prior treatment lines. The median number of previous
      treatment lines was three, with 61% of the patients having received more than
      three lines (including rituximab in 47%). After a median follow-up of 76 months
      (range, 14-160), three patients developed secondary myelodysplastic syndrome. The
      5-year overall survival rate was 71% and 5-year time-to-progression was 44%.
      There were no differences in time-to-progression or overall survival according to
      the number of previous treatment lines or episodes of disease. In conclusion,
      high-dose therapy with autologous stem cell rescue with BEAM appears to be
      equally effective in second or third remission of follicular lymphoma.

PMID- 23144202
TI  - Adherence to the Mediterranean dietary pattern and heart rate in the SUN project.
AB  - BACKGROUND: A higher heart rate has been related to an increase of total and
      cardiovascular mortality. The aim of this study was to assess the relation
      between adherence to the Mediterranean diet and heart rate. DESIGN: The SUN
      project is an ongoing multipurpose cohort study based on university graduates
      from Spain. METHODS: This cross-sectional study included 15,863 participants of
      the SUN project. Adherence to the Mediterranean dietary pattern was assessed
      through a validated 136-item food frequency questionnaire and calculated
      according to the 9-point score proposed by Trichopoulou. Multiple linear
      regression models were fitted to assess the relationship between adherence to the
      Mediterranean dietary pattern and heart rate and 95% confidence intervals were
      calculated. RESULTS: The multivariable-adjusted models revealed that participants
      with a high adherence (7--9 points) to the Mediterranean dietary pattern had a
      heart rate 2.2 bpm (95% CI 1.4-3.1) lower than participants with a low adherence
      (0--2 points). CONCLUSIONS: Adherence to the Mediterranean dietary pattern seems
      to be related to a lower heart rate.

PMID- 23144203
TI  - Evaluation of the NexScreen and DrugCheck Waive RT urine drug detection cups.
AB  - Urine drug testing is an important tool that is commonly used to assess patient
      compliance with prescription regimens. Point-of-collection immunoassay devices
      allow for timely availability of laboratory test results to guide therapy during
      the same office visit. Two waived immunoassay-based urine drug screen cups were
      evaluated in this study. The NexScreen cup and the DrugCheck Waive RT cup claim
      to detect 10-12 drug classes of commonly used and/or abused drugs. This study
      included a sensitivity and precision challenge with 4-6 replicates at
      concentrations 0-150% of the manufacture's claimed cutoff, using drug-free urine
      spiked with purified reference standards. The stability of test results was
      evaluated by reading the results at intervals between five and 1,440 min.
      Specificity was evaluated by parallel comparison of pooled patients' specimens,
      representing 56 patients and 41 known drug compounds. When comparing results to
      validated liquid chromatography-mass spectrometry results, false positives were
      observed in the NexScreen cups for benzodiazepine, methamphetamine, methadone,
      opiates and tricyclic antidepressant tests, but there were no false negatives.
      The DrugCheck Waive RT cups showed false negative results for barbiturates and
      opiates, but no false positives. Overall, the NexScreen cup demonstrated better
      sensitivity than claimed, whereas the sensitivity of the DrugCheck Waive RT cup
      did not meet claims.

PMID- 23144204
TI  - For-profit sector immunization service provision: does low provision create a
      barrier to take-up?
AB  - Achievement of the health-related Millennium Development Goals is dependent on
      increasing take-up of preventive public health services (PHSs) in developing
      countries. Poor country governments often lack the resources to provide optimal
      access to preventive services and a great deal of attention is being directed
      towards the private sector to fill this void. In many developing countries, the
      private sector already plays a large role in health care. However, the for-profit
      private sector has little incentive to provide PHSs. The lack of provision of
      services by the for-profit sector may create a barrier to take-up of these
      services. In this study, we use data from a census of health facilities combined
      with data from community and provider surveys from Kenya to analyse whether the
      private for-profit sector has lower provision rates of child immunization
      services, and subsequently whether this creates a barrier that results in lower
      immunization take-up. We show that only 34% of for-profit facilities provide
      immunizations and that in areas with a larger share of for-profit providers,
      children are more likely to have no immunization coverage. Our model predicts
      that the odds of a child receiving no immunization coverage are 4.8 times higher
      in areas where all health facilities are for-profit compared to areas with no for
      profit facilities. This indicates that a policy of engagement with the private
      for-profit sector aimed at increasing provision of immunization services may be
      an effective strategy for increasing take-up. 

PMID- 23144205
TI  - Protective effect of K201 on isoproterenol-induced and ischemic-reperfusion
      induced ventricular arrhythmias in the rat: comparison with diltiazem.
AB  - AIM: Ventricular arrhythmia (VA) is a risk for sudden death. Polymorphic
      ventricular tachycardia (VT) degenerating to ventricular fibrillation occurs
      subsequent to the prolongation of the QT interval following administration of
      catecholamines under Ca(2+) loading. Fatal VA also occurs in ischemia and
      ischemic-reperfusion. We compared the suppressive effect of K201 (JTV519), a
      multiple-channel blocker and cardiac ryanodine receptor-calcium release channel
      (RyR2) stabilizer, with that of diltiazem, a Ca(2+ )channel blocker, in 2 studies
      of isoproterenol-induced (n = 30) and ischemic-reperfusion-induced VAs (n = 38)
      in rats. METHODS: Adult male Wistar rats were administered 12 mg/kg/min calcium
      chloride (CaCl(2)) for 20 minutes and then 6 MUg/kg/min isoproterenol was infused
      with CaCl(2) for a further 20 minutes. In other rats, the left coronary artery
      was ligated for 5 minutes followed by reperfusion for 20 minutes. K201 or
      diltiazem (both 1 mg/kg) was administered before infusion of the isoproterenol or
      induction of ischemia. RESULTS: After administration of isoproterenol under
      Ca(2+) loading, fatal VA frequently occurred in the vehicle (9 of 10 animals,
      90%) and diltiazem (8 of 10, 80%) groups, and K201 significantly suppressed the
      incidences of arrhythmia and mortality (2 of 10, 20%). In the reperfusion study,
      the incidence and the time until occurrence of reperfusion-induced VA and
      mortality were significantly suppressed in the K201 (2 of 15 animals, 13%) and
      diltiazem (1 of 9 animals, 11%) groups compared to the vehicle group (8 of 14
      animals, 57%). SIGNIFICANCE: Induction of VA in an experimental model was
      achieved with a low dose of isoproterenol under Ca(2+) loading. K201 markedly
      suppressed both the isoproterenol-induced and the reperfusion-induced VAs,
      whereas diltiazem did not suppress the isoproterenol-induced VA. The results
      suggest that both VAs are related to early after depolarization (EAD) and
      indicate that K201 has the potential to suppress EAD by stabilizing RyR2 to
      mediate Ca(2+) release from the sarcoplasmic reticulum and acting as a multiple
      channel blocker.

PMID- 23144206
TI  - Does mindfulness based cognitive therapy prevent relapse of depression?

PMID- 23144207
TI  - Visual agnosia.

PMID- 23144208
TI  - Thoracic outlet syndrome.

PMID- 23144209
TI  - Call for worldwide withdrawal of tiotropium Respimat mist inhaler.

PMID- 23144211
TI  - Oblique radiograph of the normal lumbar spine.

PMID- 23144213
TI  - Daily multivitamins do not protect against cardiovascular events, finds study.

PMID- 23144215
TI  - Californians vote to keep the death penalty.

PMID- 23144216
TI  - Complaints about removal from GP lists rise by 16% in a year.

PMID- 23144217
TI  - Fragmenting consciousness.

PMID- 23144219
TI  - Activated drying in hydrophobic nanopores and the line tension of water.
AB  - We study the slow dynamics of water evaporation out of hydrophobic cavities by
      using model porous silica materials grafted with octylsilanes. The cylindrical
      pores are monodisperse, with a radius in the range of 1-2 nm. Liquid water
      penetrates in the nanopores at high pressure and empties the pores when the
      pressure is lowered. The drying pressure exhibits a logarithmic growth as a
      function of the driving rate over more than three decades, showing the thermally
      activated nucleation of vapor bubbles. We find that the slow dynamics and the
      critical volume of the vapor nucleus are quantitatively described by the
      classical theory of capillarity without adjustable parameter. However, classical
      capillarity utterly overestimates the critical bubble energy. We discuss the
      possible influence of surface heterogeneities, long-range interactions, and high
      curvature effects, and we show that a classical theory can describe vapor
      nucleation provided that a negative line tension is taken into account. The
      drying pressure then provides a determination of this line tension with much
      higher precision than currently available methods. We find consistent values of
      the order of -30 pN in a variety of hydrophobic materials.

PMID- 23144218
TI  - Arabidopsis ribosomal proteins control developmental programs through
      translational regulation of auxin response factors.
AB  - Upstream ORFs are elements found in the 5'-leader sequences of specific mRNAs
      that modulate the translation of downstream ORFs encoding major gene products. In
      Arabidopsis, the translational control of auxin response factors (ARFs) by
      upstream ORFs has been proposed as a regulatory mechanism required to respond
      properly to complex auxin-signaling inputs. In this study, we identify and
      characterize the aberrant auxin responses in specific ribosomal protein mutants
      in which multiple ARF transcription factors are simultaneously repressed at the
      translational level. This characteristic lends itself to the use of these mutants
      as genetic tools to bypass the genetic redundancy among members of the ARF family
      in Arabidopsis. Using this approach, we were able to assign unique functions for
      ARF2, ARF3, and ARF6 in plant development.

PMID- 23144220
TI  - Opening the gate to working memory.

PMID- 23144221
TI  - Optimality and robustness in quorum sensing (QS)-mediated regulation of a costly
      public good enzyme.
AB  - Bacteria secrete a variety of public good exoproducts into their environment.
      These exoproducts are typically produced under the control of quorum sensing
      (QS), a signaling mechanism by which bacteria sense and respond to changes in
      their density. QS seems to provide an advantageous strategy to regulate these
      costly but beneficial exoproducts: it delays production until sufficiently high
      cell density, when the overall benefit of exoproducts outweighs cost of their
      production. This notion raises several fundamental questions about QS as a
      general control strategy adopted by bacteria. How much delay is advantageous?
      Under what conditions does QS-mediated regulation become advantageous? How does
      this advantage depend on the kinetic properties of QS? How robust is a given QS
      system to the stochastic events that occur over bacterial lifecycles? To
      quantitatively address these questions, we engineered a gene circuit in
      Escherichia coli to control the synthesis and secretion of a costly but
      beneficial exoenzyme. We show that exoenzyme production is overall advantageous
      only if initiated at a sufficiently high density. This property sets the
      potential advantage for QS-mediated regulation when the initial density is low
      and the growth cycle is sufficiently long compared with the exoenzyme response
      time. This advantage of QS-mediated regulation is robust to varying initial cell
      densities and growth durations, and it is particularly striking when bacteria
      face uncertainty, such as from stochastic dispersal during their lifecycle. We
      show, however, that, for QS to be optimal, its kinetic properties must be
      appropriately tuned; this property has implications for antibacterial treatments
      that target QS.

PMID- 23144222
TI  - Quantum teleportation between remote atomic-ensemble quantum memories.
AB  - Quantum teleportation and quantum memory are two crucial elements for large-scale
      quantum networks. With the help of prior distributed entanglement as a "quantum
      channel," quantum teleportation provides an intriguing means to faithfully
      transfer quantum states among distant locations without actual transmission of
      the physical carriers [Bennett CH, et al. (1993) Phys Rev Lett 70(13):1895-1899].
      Quantum memory enables controlled storage and retrieval of fast-flying photonic
      quantum bits with stationary matter systems, which is essential to achieve the
      scalability required for large-scale quantum networks. Combining these two
      capabilities, here we realize quantum teleportation between two remote atomic
      ensemble quantum memory nodes, each composed of ~10(8) rubidium atoms and
      connected by a 150-m optical fiber. The spin wave state of one atomic ensemble is
      mapped to a propagating photon and subjected to Bell state measurements with
      another single photon that is entangled with the spin wave state of the other
      ensemble. Two-photon detection events herald the success of teleportation with an
      average fidelity of 88(7)%. Besides its fundamental interest as a teleportation
      between two remote macroscopic objects, our technique may be useful for quantum
      information transfer between different nodes in quantum networks and distributed
      quantum computing.

PMID- 23144224
TI  - Offering older hospitalised patients the choice to die in their preferred place.
AB  - BACKGROUND: A significant proportion of older people state a preference to die at
      home. However, the vast majority of people in hospital recognised as dying
      subsequently die there. OBJECTIVES: To identify the proportion of older people
      dying in hospital where the possibility of ending life elsewhere was explored. To
      identify factors that could support hospital staff to enable patients' wishes to
      be met. METHODS: Retrospective case-note review of 100 older patients (>75 years)
      who died during 2009 in an English Hospital. RESULTS: Age range 75-97 years. Time
      from admission to death ranged from 0-118 days (median 8.5). 16% died within the
      first 48 h, rising to 30% for those from care homes. In only 8 patients was a
      potential alternative place of death discussed. Although subjective, in 10
      patients it was considered admission could have been avoided through Advance Care
      Planning (ACP) to allow patients with poor prognosis to die in their normal place
      of residence or a hospice. 55% of Do-Not-Attempt-Resuscitation orders were made
      within 48 h of admission. 38% were commenced on the Liverpool Care Pathway (LCP),
      1-504 h before death (median 16). CONCLUSIONS: In few cases are the preferred
      places of death discussed in older people who die in our hospital. Although
      hospital admission was largely appropriate, in a minority judicious ACP could
      have avoided death in hospital. We recommend (1) increased use of ACP, with
      appropriate practicalities planned in advance (2) wide-scale introduction of the
      'Rapid Discharge Home of the Dying Patient pathway' (3) routinely discussing
      preferred place of death in appropriate key situations (eg, discussion of
      resuscitation status or commencing the LCP).

PMID- 23144223
TI  - A network of genetic repression and derepression specifies projection fates in
      the developing neocortex.
AB  - Neurons within each layer in the mammalian cortex have stereotypic projections.
      Four genes-Fezf2, Ctip2, Tbr1, and Satb2-regulate these projection identities.
      These genes also interact with each other, and it is unclear how these
      interactions shape the final projection identity. Here we show, by generating
      double mutants of Fezf2, Ctip2, and Satb2, that cortical neurons deploy a complex
      genetic switch that uses mutual repression to produce subcortical or callosal
      projections. We discovered that Tbr1, EphA4, and Unc5H3 are critical downstream
      targets of Satb2 in callosal fate specification. This represents a unique role
      for Tbr1, implicated previously in specifying corticothalamic projections. We
      further show that Tbr1 expression is dually regulated by Satb2 and Ctip2 in
      layers 2-5. Finally, we show that Satb2 and Fezf2 regulate two disease-related
      genes, Auts2 (Autistic Susceptibility Gene2) and Bhlhb5 (mutated in Hereditary
      Spastic Paraplegia), providing a molecular handle to investigate circuit
      disorders in neurodevelopmental diseases.

PMID- 23144225
TI  - Does a falling level of activity predict disability development in community
      dwelling elderly people?
AB  - OBJECTIVE: To investigate the predictive value of self-reported decline in
      weight, exhaustion, walking difficulty, grip strength and physical activity on
      development of disabilities in community-dwelling elderly people. DESIGN: A one
      year follow-up study. SETTING: Participants were recruited via four Dutch general
      practitioners. PARTICIPANTS: Community-dwelling elderly people aged 70 years or
      older. METHODS: A total of 687 participants received a questionnaire at baseline
      regarding weight loss, exhaustion, walking difficulty, grip strength, physical
      activity and disability. The same questionnaire was sent to them after one year
      follow-up. Disability was operationalized in two ways: as increased dependence
      and as increased difficulty in daily activities. Univariate and multivariate
      logistic regression analyses were used to determine whether self-reported decline
      in five physical indicators at baseline predicted development of dependence or
      increased difficulty in daily activities after one year. The analyses were
      controlled for age, gender and baseline disability. RESULTS: Four hundred and one
      participants with a mean age of 76.9 years (SD 5.2) were included in the
      analyses. Eighty-four of them reported increased dependence (21%) and 76 reported
      increased difficulty (19%) in daily activities at one-year follow-up. All
      physical indicators, except weight loss, were significant univariate predictors
      of disability. Multivariate analyses revealed that self-reported decrease in
      physical activity (e.g. walking, cycling, gardening) was a significant predictor
      of development of dependence (odds ratio (OR) = 1.89, 95% confidence interval
      (CI) = 1.02-3.51) and development of difficulty (OR = 1.98, 95% CI = 1.05-3.71)
      in daily activities. CONCLUSION: Community-dwelling elderly people who report
      decreased physical activity have a higher risk to develop disability at one-year
      follow-up.

PMID- 23144226
TI  - Fall risk six weeks from onset of stroke and the ability of the Prediction of
      Falls in Rehabilitation Settings Tool and motor function to predict falls.
AB  - OBJECTIVE: To investigate whether the Prediction of Falls in Rehabilitation
      Settings Tool (Predict FIRST) and motor function could be used to identify people
      at risk of falling during the first six weeks after stroke, and to compare the
      risk of falling according to Predict FIRST with real falls frequency. DESIGN: A
      longitudinal, prospective study. PATIENTS: Sixty-eight people newly diagnosed
      with stroke admitted to an acute stroke unit. METHODS: The participants underwent
      an assessment of motor ability (Modified Motor Assessment Scale according to
      Uppsala University Hospital version 99 (M-MAS UAS-99)) and falls risk (Predict
      FIRST) on the first to fourth day at the acute stroke unit. Falls occurring in
      the acute stroke unit were recorded and falls occurring after discharge were
      reported by telephone follow-up. The prediction of falls was analysed with binary
      logistic regression. RESULTS: Fourteen of the patients (21%) fell at least once
      during the first six weeks after stroke. The strongest significant predictor for
      falls was a high score on Predict FIRST (odds ratio 5.21, confidence interval
      (CI) 1.10-24.78) followed by M-MAS UAS-99 parts C-E (odds ratio 0.65, CI 0.44
      0.95). Predict FIRST underestimated the risk of falling as the median fall risk
      was 9% according to Predict FIRST. CONCLUSION: Although Predict FIRST has the
      ability to predict falls in people with recent onset of stroke, there is some
      underestimation of fall risk.

PMID- 23144227
TI  - Free formula milk in the prevention of mother-to-child transmission programme:
      voices of a peri-urban community in South Africa on policy change.
AB  - BACKGROUND: In 2001, South Africa began implementing the Prevention of Mother-to
      Child Transmission of HIV (PMTCT) programme. This programme included distribution
      of free formula milk for infants up to 6 months of age at all public health
      facilities. Effective from 1 January 2011, KwaZulu-Natal became the first
      province to phase out free formula milk from its PMTCT programme. On 23 August
      2011, the South African National Department of Health adopted promotion of
      exclusive breastfeeding as the national infant feeding strategy and made a
      decision to withdraw free formula milk from the PMTCT programme. OBJECTIVE: To
      explore the perceptions and understanding of households at community level on the
      policy decision to phase out free formula milk from the PMTCT programme in South
      Africa. METHODS: An exploratory qualitative study was conducted amongst women
      enrolled in a community randomized trial known as Good Start III. Focus group
      discussions were held with grandmothers, fathers and teenage mothers; and in
      depth interviews were performed with HIV-positive and HIV-negative mothers. Data
      were analysed using thematic analysis. RESULTS: Identified themes included: (1)
      variations in awareness and lack of understanding of the basis for the policy
      change, (2) abuse of and dysfunctional policy as perceived reasons for policy
      change and (3) proposed strategies for communicating the policy change.
      CONCLUSION: There is an urgent need to develop a multifaceted communication
      strategy clearly articulating the reasons for the infant feeding policy change
      and promoting the new breastfeeding strategy. The communication strategy should
      take into account inputs from the community. With a supportive environment and
      one national infant feeding strategy, South Africa has an opportunity to reverse
      years of poor infant feeding practices and to improve the health of all children
      in the country.

PMID- 23144228
TI  - Narrowing the treatment gap with equitable access: mid-term outcomes of a
      community case management program in Cameroon.
AB  - Coverage of case management interventions remains low and inadequate to achieve
      millennium development goal (MDG) target reductions in child mortality. Children
      living in the poorest households are particularly disadvantaged. Community case
      management (CCM) uses trained and supervised community health workers to improve
      access to, quality of and demand for effective case management. Evidence that CCM
      programs can achieve equitable improvements in coverage is limited. This cross
      sectional study uses a quasi-experimental design with intervention and comparison
      areas. Outcomes of a CCM program for malaria and diarrhoea operating in two
      districts of Cameroon were measured after 1 year of implementation. A household
      census (N = 16 954) provided measurement of treatment-seeking behaviour for
      recent episodes of fever and diarrhoea. Results were compared between areas using
      chi-square tests. Intervention-area children with fever or diarrhoea were nearly
      nine times more likely to receive treatment with artemisinin combination therapy
      or oral rehydration salts, respectively, vs neighbouring comparison-area
      children. High levels of effective treatment were equitable across socioeconomic
      status in intervention areas, whereas disparities were observed in neighbouring
      comparison areas. CCM can achieve rapid and equitable improvements in coverage of
      case management for malaria and diarrhoea, and is a promising strategy for
      achieving MDG 4. Improved access to treatment, quality of care and caregiver
      demand were achieved in two districts of Cameroon. CCM must be scaled up to
      demonstrate outcomes and impact at scale. 

PMID- 23144229
TI  - Transforming governance or reinforcing hierarchies and competition: examining the
      public and hidden transcripts of the Global Fund and HIV in India.
AB  - Global health initiatives (GHIs) have gained prominence as innovative and
      effective policy mechanisms to tackle global health priorities. More recent
      literature reveals governance-related challenges and their unintended health
      system effects. Much less attention is received by the relationship between these
      mechanisms, the ideas that underpin them and the country-level practices they
      generate. The Global Fund has leveraged significant funding and taken a lead in
      harmonizing disparate efforts to control HIV/AIDS. Its growing influence in
      recipient countries makes it a useful case to examine this relationship and
      evaluate the extent to which the dominant public discourse on Global Fund departs
      from the hidden resistances and conflicts in its operation. Drawing on insights
      from ethnographic fieldwork and 70 interviews with multiple stakeholders, this
      article aims to better understand and reveal the public and the hidden transcript
      of the Global Fund and its activities in India. We argue that while its public
      transcript abdicates its role in country-level operations, a critical
      ethnographic examination of the organization and governance of the Fund in India
      reveals a contrasting scenario. Its organizing principles prompt diverse actors
      with conflicting agendas to come together in response to the availability of
      funds. Multiple and discrete projects emerge, each leveraging control and
      resources and acting as conduits of power. We examine how management of HIV is
      punctuated with conflicts of power and interests in a competitive environment set
      off by the Fund protocol and discuss its system-wide effects. The findings also
      underscore the need for similar ethnographic research on the financing and policy
      making architecture of GHIs. 

PMID- 23144230
TI  - Income elasticity of health expenditures in Iran.
AB  - Because of its policy implications, the income elasticity of health care
      expenditures is a subject of much debate. Governments may have an interest in
      subsidizing the care of those with low income. Using more than two decades of
      data from the Iran Household Expenditure and Income Survey, this article
      investigates the relationship between income and health care expenditure in urban
      and rural areas in Iran, a resource rich, upper-middle-income country. We
      implemented spline and quantile regression techniques to obtain a more robust
      description of the relationship of interest. This study finds non-uniform effects
      of income on health expenditures. Although the results show that health care is a
      necessity for all income brackets, spline regression estimates indicate that the
      income elasticity is lowest for the poorest Iranians in urban and rural areas.
      This suggests that they will show low flexibility in medical expenses as income
      fluctuates. Further, a quantile regression model assessing the effect of income
      at different level of medical expenditure suggests that households with lower
      medical expenses are less elastic. 

PMID- 23144231
TI  - Doctors will be key to raising productivity levels to plug shortages in
      workforce.

PMID- 23144232
TI  - Breast surgeon is investigated by GMC over allegations of unnecessary surgery.

PMID- 23144233
TI  - Patients are failing to get new drugs even when approved by NICE, industry chief
      says.

PMID- 23144234
TI  - Climate change experts need funds to research vital questions, conference hears.

PMID- 23144236
TI  - Vicious cycles: digital technologies and determinants of health in Australia.
AB  - Digital technologies are increasingly important as ways to gain access to most of
      the important social determinants of health including employment, housing,
      education and social networks. However, little is known about the impact of the
      new technologies on opportunities for health and well-being. This paper reports
      on a focus group study of the impact of these technologies on people from low
      socio-economic backgrounds. We use Bourdieu's theories of social inequities and
      the ways in which social, cultural and economic capitals interact to reinforce
      and reproduce inequities to examine the ways in which digital technologies are
      contributing to these processes. Six focus group discussions with 55 people were
      held to examine their access to and views about using digital technologies. These
      data are analysed in light of Bourdieu's theory to determine how people's
      existing capitals shape their access to and use of digital technologies and what
      the implications of exclusion from the technologies are likely to be for the
      social determinants of health. The paper concludes that some people are being
      caught in a vicious cycle whereby lack of digital access or the inability to make
      beneficial use reinforces and amplifies existing disadvantage including low
      levels of reading and writing literacy. The paper concludes with a consideration
      of actions health promoters could take to interrupt this cycle and so contribute
      to reducing health inequities. 

PMID- 23144237
TI  - Antitumor activity of saracatinib (AZD0530), a c-Src/Abl kinase inhibitor, alone
      or in combination with chemotherapeutic agents in gastric cancer.
AB  - Src is a nonreceptor tyrosine kinase involved in the cross-talk and mediation of
      many signaling pathways that promote cell proliferation, adhesion, invasion,
      migration, and tumorigenesis. Increased Src activity has been reported in many
      types of human cancer, including gastric cancer. Therefore, this factor has been
      identified as a promising therapeutic target for cancer treatments, and targeting
      Src in gastric cancer is predicted to have potent effects. We evaluated the
      antitumor effect of a c-Src/Abl kinase inhibitor, saracatinib (AZD0530), alone or
      combined with chemotherapeutic agents in gastric cancer cell lines and a NCI-N87
      xenograft model. Among 10 gastric cancer cell lines, saracatinib specifically
      inhibited the growth and migration/invasion of SNU216 and NCI-N87 cells.
      Saracatinib blocked the Src/FAK, HER family, and oncogenic signaling pathways,
      and it induced G(1) arrest and apoptosis in SNU216 and NCI-N87 cells. Apoptosis
      required induction of the proapoptotic BCL2 family member Bim. Knockdown of Bim
      using siRNA decreased apoptosis induced by treatment with saracatinib, suggesting
      that Bim has an important role in saracatinib-induced apoptosis. Saracatinib
      enhanced the effects of lapatinib, an EGFR/HER2 dual inhibitor, in SNU216 and NCI
      N87 cells. Furthermore, combined treatment with saracatinib and 5-fluorouracil (5
      FU) or cisplatin exerted synergistic effects in both saracatinib-sensitive and
      saracatinib-resistant cells. Consistent with our in vitro findings, cotreatment
      with saracatinib and 5-FU resulted in enhanced antitumor activity in the NCI-N87
      xenografts. These data indicate that the inhibition of Src kinase activity by
      saracatinib alone or in combination with other agents can be a strategy to target
      gastric cancer.

PMID- 23144239
TI  - Evaluation of antioxidant, rheological, physical and sensorial properties of
      wheat flour dough and cake containing turmeric powder.
AB  - The effects of addition of turmeric powder (0%, 2%, 4%, 6% and 8%) were examined
      in order to obtain an antioxidant-enriched cake with good physico-chemical and
      sensorial properties. The rheological properties of doughs were evaluated using
      dynamic rheological measurements. Physical properties, curcumin content, radical
      scavenging activity (RSA-DPPH assay) and sensory analysis (hedonic test) of the
      supplemented cake were determined. Addition of turmeric powder up to 8% caused
      significant changes on dough characteristics and on cake rheological properties.
      The highest curcumin (203 mg/kg) and RSA-DPPH activity (45%) were achieved in the
      cake having the highest percentage of turmeric powder (8%); however, this sample
      showed the worst results regarding the rheological properties. Moreover, by
      sensory evaluation this cake sample was not acceptable. A 6% substitution of
      wheat flour with turmeric powder showed acceptable sensory scores which were
      comparable to those of 0-4% turmeric cakes. This indicated that up to 6% level of
      turmeric powder might be included in cake formulation.

PMID- 23144238
TI  - Noncompetitive, voltage-dependent NMDA receptor antagonism by hydrophobic anions.
AB  - NMDA receptor (NMDAR) antagonists are dissociative anesthetics, drugs of abuse,
      and are of therapeutic interest in neurodegeneration and neuropsychiatric
      disease. Many well-known NMDAR antagonists are positively charged, voltage
      dependent channel blockers. We recently showed that the hydrophobic anion
      dipicrylamine (DPA) negatively regulates GABA(A) receptor function by a mechanism
      indistinguishable from that of sulfated neurosteroids. Because sulfated
      neurosteroids also modulate NMDARs, here we examined the effects of DPA on NMDAR
      function. In rat hippocampal neurons DPA inhibited currents gated by 300 uM NMDA
      with an IC(50) of 2.3 uM. Neither onset nor offset of antagonism exhibited
      dependence on channel activation but exhibited a noncompetitive profile. DPA
      antagonism was independent of NMDAR subunit composition and was similar at
      extrasynaptic and total receptor populations. Surprisingly, similar to cationic
      channel blockers but unlike sulfated neurosteroids, DPA antagonism was voltage
      dependent. Onset and offset of DPA antagonism were nearly 10-fold faster than DPA
      induced increases in membrane capacitance, suggesting that membrane interactions
      do not directly explain antagonism. Furthermore, voltage dependence did not
      derive from association of DPA with a site on NMDARs directly accessible to the
      outer membrane leaflet, assessed by DPA translocation experiments. Consistent
      with the expected lack of channel block, DPA antagonism did not interact with
      permeant ions. Therefore, we speculate that voltage dependence may arise from
      interactions of DPA with the inherent voltage dependence of channel gating.
      Overall, we conclude that DPA noncompetitively inhibits NMDA-induced current by a
      novel voltage-dependent mechanism and represents a new class of anionic NMDAR
      antagonists.

PMID- 23144240
TI  - Development of functional milk desserts enriched with resistant starch based on
      consumers' perception.
AB  - Sensory characteristics play a key role in determining consumers' acceptance of
      functional foods. In this context, the aim of the present work was to apply a
      combination of sensory and consumer methodologies to the development of chocolate
      milk desserts enriched with resistant starch. Chocolate milk desserts containing
      modified waxy maize starch were formulated with six different concentrations of
      two types of resistant starch (which are part of insoluble dietary fiber). The
      desserts were evaluated by trained assessors using Quantitative Descriptive
      Analysis. Moreover, consumers scored their overall liking and willingness to
      purchase and answered an open-ended question. Resistant starch caused significant
      changes in the sensory characteristics of the desserts and a significant decrease
      in consumers' overall liking and willingness to purchase. Consumer data was
      analyzed applying survival analysis on overall liking scores, considering the
      risk on consumers liking and willing to purchase the functional products less
      than their regular counterparts. The proposed methodologies proved to be useful
      to develop functional foods taking into account consumers' perception, which
      could increase their success in the market.

PMID- 23144241
TI  - Optimization of microwave vacuum drying of lotus (Nelumbo nucifera Gaertn.) seeds
      by response surface methodology.
AB  - Drying is the main process used to treat lotus seeds for storage. In this study,
      response surface methodology was used to optimize processing methods for
      microwave vacuum (MWV) drying of lotus seeds and to create a desirable product. A
      central composite design with three important factors: microwave output power
      (2.0-4.0 kW), vacuum degree (-0.070 to -0.090 MPa) and on/off ratio (68/52 s to
      99/21 s) was used to study the response variables of drying time, shrinkage
      ratio, rehydration ratio and whiteness index. The optimum conditions for MWV
      drying of lotus seeds were determined to obtain a minimal drying time, minimal
      shrinkage ratio, maximum rehydration ratio and maximum whiteness index. The
      optimum drying conditions were found to be: microwave output power 3.2 kW, vacuum
      degree -0.083 MPa and on/off ratio 94/26 s. Under these optimal conditions,
      drying time, shrinkage ratio, rehydration ratio and whiteness index were found to
      be 10 min, 37.66%, 157.1% and 68.83, respectively.

PMID- 23144242
TI  - Cassava starch as a stabilizer of soy-based beverages.
AB  - Soy-based beverages are presented as healthy food alternatives for human
      nutrition. Cassava (Manihot esculenta, Crantz) starch is relatively inexpensive,
      widely available in Brazil and is broadly used by the food industry due to its
      desired properties that result from pasting. The objective of this study was to
      develop soy-based beverages with good sensory quality using native cassava starch
      as a stabilizer and maintaining the nutritional value that makes this product a
      functional food. The developed formulations featured a range of cassava starch
      and soybean extract concentrations, which were tested in a 22 experimental design
      with three central points. The results of sensory analysis showed that the
      studied variables (cassava starch and soybean extract concentrations) did not
      have a significant effect with respect to a 5% probability level. When
      considering the apparent viscosity, on the other hand, the variables had a
      significant effect: the increase in soybean extract and cassava starch
      concentrations caused an increase in the viscosity of the final product. The
      profile of isoflavones in the tested formulations was similar to the profiles
      reported in other papers, with a predominance of the conjugated glycosides over
      the aglycone forms.

PMID- 23144243
TI  - Pseudomonas syringae pv. tomato DC3000 CmaL (PSPTO4723), a DUF1330 family member,
      is needed to produce L-allo-isoleucine, a precursor for the phytotoxin
      coronatine.
AB  - Pseudomonas syringae pv. tomato DC3000 produces the phytotoxin coronatine, a
      major determinant of the leaf chlorosis associated with DC3000 pathogenesis. The
      DC3000 PSPTO4723 (cmaL) gene is located in a genomic region encoding type III
      effectors; however, it promotes chlorosis in the model plant Nicotiana
      benthamiana in a manner independent of type III secretion. Coronatine is produced
      by the ligation of two moieties, coronafacic acid (CFA) and coronamic acid (CMA),
      which are produced by biosynthetic pathways encoded in separate operons. Cross
      feeding experiments, performed in N. benthamiana with cfa, cma, and cmaL mutants,
      implicate CmaL in CMA production. Furthermore, analysis of bacterial supernatants
      under coronatine-inducing conditions revealed that mutants lacking either the cma
      operon or cmaL accumulate CFA rather than coronatine, supporting a role for CmaL
      in the regulation or biosynthesis of CMA. CmaL does not appear to regulate CMA
      production, since the expression of proteins with known roles in CMA production
      is unaltered in cmaL mutants. Rather, CmaL is needed for the first step in CMA
      synthesis, as evidenced by the fact that wild-type levels of coronatine
      production are restored to a DeltacmaL mutant when it is supplemented with 50
      MUg/ml l-allo-isoleucine, the starting unit for CMA production. cmaL is found in
      all other sequenced P. syringae strains with coronatine biosynthesis genes. This
      characterization of CmaL identifies a critical missing factor in coronatine
      production and provides a foundation for further investigation of a member of the
      widespread DUF1330 protein family.

PMID- 23144244
TI  - FliW and FliS function independently to control cytoplasmic flagellin levels in
      Bacillus subtilis.
AB  - The cytoplasmic level of flagellin (called Hag) is homeostatically regulated in
      the Gram-positive bacterium Bacillus subtilis by a partner-switching mechanism
      between the protein FliW and either the Hag structural protein or CsrA, an RNA
      binding protein that represses hag translation. Here we show that FliW and the
      putative secretion chaperone FliS bind to Hag simultaneously but control Hag
      translation by different mechanisms. While FliW directly inhibits CsrA activity,
      FliS antagonizes CsrA indirectly by binding to Hag, enhancing Hag secretion, and
      depleting Hag in the cytoplasm to trigger the FliW partner switch. Consistent
      with a role for FliS in potentiating Hag secretion, the mutation of fliS crippled
      both motility and flagellar filament assembly, and both phenotypes could be
      partially rescued by artificially increasing the concentration of the Hag
      substrate through the absence of CsrA. Furthermore, the absence of FliS resulted
      in an approximately 30-fold reduction in extracellular Hag accumulation in cells
      mutated for CsrA (to relieve homeostatic control) and the filament cap protein
      FliD (to secrete flagellin into the supernatant). Thus, we mechanistically
      discriminate between the FliW regulator and the FliS chaperone to show that
      secretion disrupts flagellin homeostasis and promotes high-level flagellin
      synthesis during the period of filament assembly in B. subtilis.

PMID- 23144245
TI  - Characterization of BreR interaction with the bile response promoters breAB and
      breR in Vibrio cholerae.
AB  - The Vibrio cholerae BreR protein is a transcriptional repressor of the breAB
      efflux system operon, which encodes proteins involved in bile resistance. In a
      previous study (F. A. Cerda-Maira, C. S. Ringelberg, and R. K. Taylor, J.
      Bacteriol. 190:7441-7452, 2008), we used gel mobility shift assays to determine
      that BreR binds at two independent binding sites at the breAB promoter and a
      single site at its own promoter. Here it is shown, by DNase I footprinting and
      site-directed mutagenesis, that BreR is able to bind at a distal and a proximal
      site in the breAB promoter. However, only one of these sites, the proximal 29-bp
      site, is necessary for BreR-mediated transcriptional repression of breAB
      expression. In addition, it was determined that BreR represses its own expression
      by recognizing a 28-bp site at the breR promoter. These sites comprise regions of
      dyad symmetry within which residues critical for BreR function could be
      identified. The BreR consensus sequence AANGTANAC-N(6)-GTNTACNTT overlaps the -35
      region at both promoters, implying that the repression of gene expression is
      achieved by interfering with RNA polymerase binding at these promoters.

PMID- 23144246
TI  - Are there acyl-homoserine lactones within mammalian intestines?
AB  - Many Proteobacteria are capable of quorum sensing using N-acyl-homoserine lactone
      (acyl-HSL) signaling molecules that are synthesized by LuxI or LuxM homologs and
      detected by transcription factors of the LuxR family. Most quorum-sensing species
      have at least one LuxR and one LuxI homolog. However, members of the Escherichia,
      Salmonella, Klebsiella, and Enterobacter genera possess only a single LuxR
      homolog, SdiA, and no acyl-HSL synthase. The most obvious hypothesis is that
      these organisms are eavesdropping on acyl-HSL production within the complex
      microbial communities of the mammalian intestinal tract. However, there is
      currently no evidence of acyl-HSLs being produced within normal intestinal
      communities. A few intestinal pathogens, including Yersinia enterocolitica, do
      produce acyl-HSLs, and Salmonella can detect them during infection. Therefore, a
      more refined hypothesis is that SdiA orthologs are used for eavesdropping on
      other quorum-sensing pathogens in the host. However, the lack of acyl-HSL
      signaling among the normal intestinal residents is a surprising finding given the
      complexity of intestinal communities. In this review, we examine the evidence for
      and against the possibility of acyl-HSL signaling molecules in the mammalian
      intestine and discuss the possibility that related signaling molecules might be
      present and awaiting discovery.

PMID- 23144247
TI  - Hypothesis: bacteria control host appetites.
AB  - To help investigate the relationship between inflammatory and other diseases and
      the composition of the gut microbiota, we propose that a positive-feedback loop
      exists between the preferences of the host for a particular dietary regimen, the
      composition of the gut microbiota that depends on this regimen, and the
      preferences of the host as influenced by the gut microbiota. We cite evidence in
      support of this hypothesis and make testable predictions.

PMID- 23144248
TI  - The nitrogenase regulatory enzyme dinitrogenase reductase ADP-ribosyltransferase
      (DraT) is activated by direct interaction with the signal transduction protein
      GlnB.
AB  - Fe protein (dinitrogenase reductase) activity is reversibly inactivated by
      dinitrogenase reductase ADP-ribosyltransferase (DraT) in response to an increase
      in the ammonium concentration or a decrease in cellular energy in Azospirillum
      brasilense, Rhodospirillum rubrum, and Rhodobacter capsulatus. The ADP-ribosyl is
      removed by the dinitrogenase reductase-activating glycohydrolase (DraG),
      promoting Fe protein reactivation. The signaling pathway leading to DraT
      activation by ammonium is still not completely understood, but the available
      evidence shows the involvement of direct interaction between the enzyme and the
      nitrogen-signaling P(II) proteins. In A. brasilense, two P(II) proteins, GlnB and
      GlnZ, were identified. We used Fe protein from Azotobacter vinelandii as the
      substrate to assess the activity of A. brasilense DraT in vitro complexed or not
      with P(II) proteins. Under our conditions, GlnB was necessary for DraT activity
      in the presence of Mg-ADP. The P(II) effector 2-oxoglutarate, in the presence of
      Mg-ATP, inhibited DraT-GlnB activity, possibly by inducing complex dissociation.
      DraT was also activated by GlnZ and by both uridylylated P(II) proteins, but not
      by a GlnB variant carrying a partial deletion of the T loop. Kinetics studies
      revealed that the A. brasilense DraT-GlnB complex was at least 18-fold more
      efficient than DraT purified from R. rubrum, but with a similar K(m) value for
      NAD(+). Our results showed that ADP-ribosylation of the Fe protein does not
      affect the electronic state of its metal cluster and prevents association between
      the Fe and MoFe proteins, thus inhibiting electron transfer.

PMID- 23144249
TI  - Structural comparison of ColH and ColG collagen-binding domains from Clostridium
      histolyticum.
AB  - Clostridium histolyticum secretes collagenases, ColG and ColH, that cause
      extensive tissue destruction in myonecrosis. The C-terminal collagen-binding
      domain (CBD) of collagenase is required for insoluble collagen fibril binding and
      subsequent collagenolysis. The high-resolution crystal structures of ColG-CBD
      (s3b) and ColH-CBD (s3) are reported in this paper. The new X-ray structure of s3
      was solved at 2.0-A resolution (R = 17.4%; R(free) = 23.3%), while the resolution
      of the previously determined s3b was extended to 1.4 A (R = 17.9%; R(free) =
      21.0%). Despite sharing only 30% sequence identity, the molecules resemble one
      another closely (root mean square deviation [RMSD] C(alpha) = 1.5 A). All but one
      residue, whose side chain chelates with Ca(2+), are conserved. The dual Ca(2+)
      binding site in s3 is completed by an unconserved aspartate. Differential
      scanning calorimetric measurements showed that s3 gains thermal stability,
      comparable to s3b, by binding to Ca(2+) (holo T(m) = 94.1 degrees C; apo T(m) =
      70.2 degrees C). holo s3 is also stabilized against chemical denaturants urea and
      guanidine HCl. The three most critical residues for collagen interaction in s3b
      are conserved in s3. The general shape of the binding pocket is retained by
      altered loop structures and side chain positions. Small-angle X-ray scattering
      data revealed that s3 also binds asymmetrically to minicollagen. Besides the
      calcium-binding sites and the collagen-binding pocket, architecturally important
      hydrophobic residues and the hydrogen-bonding network around the cis-peptide bond
      are well conserved within the metallopeptidase subfamily M9B. CBDs were
      previously shown to bind to the extracellular matrix of various tissues.
      Compactness and extreme stability in physiological Ca(2+) concentration possibly
      make both CBDs suitable for targeted growth factor delivery.

PMID- 23144250
TI  - Genetic characterization of a novel rhizobial plasmid conjugation system in
      Rhizobium leguminosarum bv. viciae strain VF39SM.
AB  - Rhizobium leguminosarum strain VF39SM contains two plasmids that have previously
      been shown to be self-transmissible by conjugation. One of these plasmids,
      pRleVF39b, is shown in this study to carry a set of plasmid transfer genes that
      differs significantly from conjugation systems previously studied in the rhizobia
      but is similar to an uncharacterized set of genes found in R. leguminosarum bv.
      trifolii strain WSM2304. The entire sequence of the transfer region on pRleVF39b
      was determined as part of a genome sequencing project, and the roles of the
      various genes were examined by mutagenesis. The transfer region contains a
      complete set of mating pair formation (Mpf) genes, a traG gene, and a relaxase
      gene, traA, all of which appear to be necessary for plasmid transfer.
      Experimental evidence suggested the presence of two putative origins of transfer
      within the gene cluster. A regulatory gene, trbR, was identified in the region
      between traA and traG and was mutated. TrbR was shown to function as a repressor
      of both trb gene expression and plasmid transfer.

PMID- 23144251
TI  - High-mobility-group a-like CarD binds to a DNA site optimized for affinity and
      position and to RNA polymerase to regulate a light-inducible promoter in
      Myxococcus xanthus.
AB  - The CarD-CarG complex controls various cellular processes in the bacterium
      Myxococcus xanthus including fruiting body development and light-induced
      carotenogenesis. The CarD N-terminal domain, which defines the large
      CarD_CdnL_TRCF protein family, binds to CarG, a zinc-associated protein that does
      not bind DNA. The CarD C-terminal domain resembles eukaryotic high-mobility-group
      A (HMGA) proteins, and its DNA binding AT hooks specifically recognize the minor
      groove of appropriately spaced AT-rich tracts. Here, we investigate the
      determinants of the only known CarD binding site, the one crucial in CarD-CarG
      regulation of the promoter of the carQRS operon (P(QRS)), a light-inducible
      promoter dependent on the extracytoplasmic function (ECF) sigma factor CarQ. In
      vitro, mutating either of the 3-bp AT tracts of this CarD recognition site
      (TTTCCAGAGCTTT) impaired DNA binding, shifting the AT tracts relative to P(QRS)
      had no effect or marginally lowered DNA binding, and replacing the native site by
      the HMGA1a binding one at the human beta interferon promoter (with longer AT
      tracts) markedly enhanced DNA binding. In vivo, however, all of these changes
      deterred P(QRS) activation in wild-type M. xanthus, as well as in a strain with
      the CarD-CarG pair replaced by the Anaeromyxobacter dehalogenans CarD-CarG
      (CarD(Ad)-CarG(Ad)). CarD(Ad)-CarG(Ad) is functionally equivalent to CarD-CarG
      despite the lower DNA binding affinity in vitro of CarD(Ad), whose C-terminal
      domain resembles histone H1 rather than HMGA. We show that CarD physically
      associates with RNA polymerase (RNAP) specifically via interactions with the RNAP
      beta subunit. Our findings suggest that CarD regulates a light-inducible, ECF
      sigma-dependent promoter by coupling RNAP recruitment and binding to a specific
      DNA site optimized for affinity and position.

PMID- 23144252
TI  - Detoxification of 7-dehydrocholesterol fatal to Helicobacter pylori is a novel
      role of cholesterol glucosylation.
AB  - The glucosylation of free cholesterol (FC) by Helicobacter pylori cells has
      various biological significances for the survival of this bacterium. H. pylori
      cells with glucosylated FC are capable of evading host immune systems, such as
      phagocytosis by macrophages and activation of antigen-specific T cells, and
      surviving in the gastric mucosal tissues for long periods. An additional role of
      cholesterol glucosylation in the survival of H. pylori which is distinct from the
      role of escaping the host immune system, however, has yet to be identified. This
      study demonstrated that 7-dehydrocholesterol (7dFC), an FC precursor, is a toxic
      compound fatal to H. pylori cells, but the cell membrane of H. pylori is capable
      of absorbing this toxic sterol via glucosylation. In contrast to the case with
      7dFC, no toxicity to H. pylori cells was detected from the glucosylated 7dFC. In
      addition, cgt gene mutant H. pylori cells that cannot glucosylate cholesterols
      had higher susceptibility to the toxic action of 7dFC than wild-type H. pylori
      cells. These results indicate that the cgt gene product of H. pylori serves to
      detoxify the sterol fatal to this bacterium and to permit this toxic sterol as a
      cell membrane lipid component. In summary, this study defined a novel role of
      cholesterol glucosylation in H. pylori.

PMID- 23144253
TI  - Flagellum density regulates Proteus mirabilis swarmer cell motility in viscous
      environments.
AB  - Proteus mirabilis is an opportunistic pathogen that is frequently associated with
      urinary tract infections. In the lab, P. mirabilis cells become long and
      multinucleate and increase their number of flagella as they colonize agar
      surfaces during swarming. Swarming has been implicated in pathogenesis; however,
      it is unclear how energetically costly changes in P. mirabilis cell morphology
      translate into an advantage for adapting to environmental changes. We
      investigated two morphological changes that occur during swarming--increases in
      cell length and flagellum density--and discovered that an increase in the surface
      density of flagella enabled cells to translate rapidly through fluids of
      increasing viscosity; in contrast, cell length had a small effect on motility. We
      found that swarm cells had a surface density of flagella that was ~5 times larger
      than that of vegetative cells and were motile in fluids with a viscosity that
      inhibits vegetative cell motility. To test the relationship between flagellum
      density and velocity, we overexpressed FlhD(4)C(2), the master regulator of the
      flagellar operon, in vegetative cells of P. mirabilis and found that increased
      flagellum density produced an increase in cell velocity. Our results establish a
      relationship between P. mirabilis flagellum density and cell motility in viscous
      environments that may be relevant to its adaptation during the infection of
      mammalian urinary tracts and movement in contact with indwelling catheters.

PMID- 23144254
TI  - The Francisella tularensis FabI enoyl-acyl carrier protein reductase gene is
      essential to bacterial viability and is expressed during infection.
AB  - Francisella tularensis is classified as a category A priority pathogen and causes
      fatal disseminated disease in humans upon inhalation of less than 50 bacteria.
      Although drugs are available for treatment, they are not ideal because of
      toxicity and route of delivery, and in some cases patients relapse upon
      withdrawal. We have an ongoing program to develop novel FAS-II FabI enoyl-ACP
      reductase enzyme inhibitors for Francisella and other select agents. To establish
      F. tularensis FabI (FtFabI) as a clinically relevant drug target, we demonstrated
      that fatty acid biosynthesis and FabI activity are essential for growth even in
      the presence of exogenous long-chain lipids and that FtfabI is not
      transcriptionally altered in the presence of exogenous long-chain lipids.
      Inhibition of FtFabI or fatty acid synthesis results in loss of viability that is
      not rescued by exogenous long-chain lipid supplementation. Importantly, whole
      genome transcriptional profiling of F. tularensis with DNA microarrays from
      infected tissues revealed that FtfabI and de novo fatty acid biosynthetic genes
      are transcriptionally active during infection. This is the first demonstration
      that the FabI enoyl-ACP-reductase enzyme encoded by F. tularensis is essential
      and not bypassed by exogenous fatty acids and that de novo fatty acid
      biosynthetic components encoded in F. tularensis are transcriptionally active
      during infection in the mouse model of tularemia.

PMID- 23144255
TI  - Cloning, expression, and functional characterization of secondary amino acid
      transporters of Lactococcus lactis.
AB  - Fourteen genes encoding putative secondary amino acid transporters were
      identified in the genomes of Lactococcus lactis subsp. cremoris strains MG1363
      and SK11 and L. lactis subsp. lactis strains IL1403 and KF147, 12 of which were
      common to all four strains. Amino acid uptake in L. lactis cells overexpressing
      the genes revealed transporters specific for histidine, lysine, arginine,
      agmatine, putrescine, aromatic amino acids, acidic amino acids, serine, and
      branched-chain amino acids. Substrate specificities were demonstrated by
      inhibition profiles determined in the presence of excesses of the other amino
      acids. Four knockout mutants, lacking the lysine transporter LysP, the histidine
      transporter HisP (formerly LysQ), the acidic amino acid transporter AcaP (YlcA),
      or the aromatic amino acid transporter FywP (YsjA), were constructed. The LysP,
      HisP, and FywP deletion mutants showed drastically decreased rates of uptake of
      the corresponding substrates at low concentrations. The same was observed for the
      AcaP mutant with aspartate but not with glutamate. In rich M17 medium, the
      deletion of none of the transporters affected growth. In contrast, the deletion
      of the HisP, AcaP, and FywP transporters did affect growth in a defined medium
      with free amino acids as the sole amino acid source. HisP was essential at low
      histidine concentrations, and AcaP was essential in the absence of glutamine.
      FywP appeared to play a role in retaining intracellularly synthesized aromatic
      amino acids when these were not added to the medium. Finally, HisP, AcaP, and
      FywP did not play a role in the excretion of accumulated histidine, glutamate, or
      phenylalanine, respectively, indicating the involvement of other transporters.

PMID- 23144256
TI  - A randomised trial comparing the clinical effectiveness of different emergency
      department healthcare professionals in soft tissue injury management.
AB  - OBJECTIVES: To evaluate the clinical effectiveness of soft tissue injury
      management by emergency nurse practitioners (ENPs) and extended scope
      physiotherapists (ESPs) compared to the routine care provided by doctors in a UK
      emergency department (ED). DESIGN: Randomised, pragmatic trial of equivalence.
      SETTING: One adult ED in England. PARTICIPANTS: 372 patients were randomised; 126
      to the ESP group, 123 to the ENP group and 123 to the doctor group. Participants
      were adults (older than 16 years) presenting to the ED with a peripheral soft
      tissue injury eligible for management by any of the three professional groups.
      Patients were excluded if they had any of the following: injury greater than 72
      hours old; systemic disease; dislocated joints; recent surgery; unable to give
      informed consent (eg, dementia), open wounds; major deformities; opiate analgesia
      required; concurrent chest/rib injury; neurovascular deficits and associated
      fracture. INTERVENTIONS: Patients were randomised to treatment by ESPs, ENPs or
      routine care provided by doctors (of all grades). MAIN OUTCOME MEASURES: Upper
      limb and lower-limb functional scores, quality of life, physical well-being,
      preference-based health measures and the number of days off work. RESULTS: The
      clinical outcomes of soft tissue injury treated by ESPs and ENPs in the ED were
      equivalent to routine care provided by doctors. CONCLUSIONS: As all groups were
      clinically equivalent it is other factors such as cost, workforce sustainability,
      service provision and skill mix that become important. This result validates the
      role of the ENP, which is becoming established as an integral part of minor
      injuries care, and demonstrates that the ESP should be considered as part of the
      clinical skill mix without detriment to outcomes.   ISRCTN-ISRCTN TRIALS REGISTER
      NUMBER:  70891354.

PMID- 23144257
TI  - Health expectancy in the occupied Palestinian territory: estimates from the Gaza
      Strip and the West Bank: based on surveys from 2006 to 2010.
AB  - OBJECTIVES: The purpose of the study was to estimate health expectancy for the
      Palestinian population and to evaluate changes that have taken place over the
      past 5 years. DESIGN: Mortality data and population-based health surveys.
      SETTING: The Israeli-occupied Palestinian territory of the Gaza Strip and the
      West Bank. PARTICIPANTS: 17 034 and 38 071 adults aged 20 or over participating
      the Palestinian Family Health Surveys of 2006 and 2010. Death rates for 2007 and
      2010 covered the entire population. OUTCOME MEASURES: Life expectancy and
      expected lifetime with and without chronic disease were estimated using the
      Sullivan method on the basis of mortality data and data on the prevalence of
      chronic disease. RESULTS: Life expectancy at the age of 20 increased from 52.8
      years in 2006 to 53.3 years in 2010 for men and from 55.1 years to 55.7 years for
      women. In 2006, expected lifetime without a chronic disease was 37.7 (95% CI 37.0
      to 38.3) years and 32.5 (95% CI 31.9 to 33.2) years for 20-year-old men and
      women, respectively. By 2010, this had decreased by 1.6 years for men and
      increased by 1.3 years for women. The health status of men has worsened. In
      particular, lifetime with hypertension and diabetes has increased. For women, the
      gain in life expectancy consisted partly of years with and partly of years
      without the most prevalent diseases. CONCLUSIONS: Health expectancy for men and
      women diverged, which could to some extent be due to gender-specific exposures
      related to lifestyle factors and the impact of military occupation.

PMID- 23144258
TI  - Regional and temporal variation in the treatment of rheumatoid arthritis across
      the UK: a descriptive register-based cohort study.
AB  - OBJECTIVES: To describe current disease-modifying antirheumatic drugs (DMARDs)
      prescription in rheumatoid arthritis (RA) with reference to best practice and to
      identify temporal and regional trends in the UK. DESIGN: Descriptive, register
      based cohort study. PARTICIPANTS: Permanently registered patients aged >=18 years
      with a recorded diagnosis of RA between 1 January 1995 and 31 March 2010 and
      matched controls. Participants with RA were identified through screening of all
      patients in the General Practice Research Database (GPRD) with a clinical or
      referral record for RA and at least 1 day of follow-up. SETTING: 639 general
      practices in the UK supplying data to the GPRD. MAIN OUTCOME MEASURES: Medication
      prescribing between 3 and 12 months of RA diagnosis by region and time period
      (1995-1999, 2000-2005 and 2006-April 2010). RESULTS: Of the 35 911 patients in
      the full RA cohort, 15 259 patients (42%) had incident RA. Analysis of
      prescribing in incident RA patients demonstrated that between 1995 (baseline) and
      2010 there was a substantial increase in DMARD, and specifically methotrexate,
      prescribing across all regions with a less marked increase in combination DMARD
      prescribing. Taking 12-month prescribing as a snapshot: DMARD prescribing was 19
      49% at baseline increasing to 45-74% by 2006-April 2010; methotrexate prescribing
      was 4-16% at baseline increasing to 32-60%; combination DMARD prescribing was 0
      8% at baseline increasing to 3-17%. However, there was marked regional variation
      in the proportion of RA patients receiving DMARD regardless of time period.
      CONCLUSIONS: There has been a substantial increase in prescribing of DMARDs for
      RA since 1995; however, regional variation persists across the UK with relative
      undertreatment, according to established best practice. Improved implementation
      of evidence-based best clinical practice to facilitate removal of treatment
      variation is warranted. This may occur as a result of the implementation of
      published national guidance.

PMID- 23144259
TI  - Estimation of cocaine consumption in the community: a critical comparison of the
      results from three complimentary techniques.
AB  - OBJECTIVES: A range of approaches are now available to estimate the level of drug
      use in the community so it is desirable to critically compare results from the
      differing techniques. This paper presents a comparison of the results from three
      methods for estimating the level of cocaine use in the general population.
      DESIGN: The comparison applies to; a set of regional-scale sample survey
      questionnaires, a representative sample survey on drug use among drivers and an
      analysis of the quantity of cocaine-related metabolites in sewage. SETTING: 14
      438 participants provided data for the set of regional-scale sample survey
      questionnaires; 2341 drivers provided oral-fluid samples and untreated sewage
      from 570 000 people was analysed for biomarkers of cocaine use. All data were
      collected in Oslo, Norway. RESULTS: 0.70 (0.36-1.03) % of drivers tested positive
      for cocaine use which suggest a prevalence that is higher than the 0.22 (0.13
      0.30) % (per day) figure derived from regional-scale survey questionnaires, but
      the degree to which cocaine consumption in the driver population follows the
      general population is an unanswered question. Despite the comparatively low
      prevalence figure the survey questionnaires did provide estimates of the volume
      of consumption that are comparable with the amount of cocaine-related metabolites
      in sewage. Per-user consumption estimates are however highlighted as a
      significant source of uncertainty as little or no data on the quantities consumed
      by individuals are available, and much of the existing data are contradictory.
      CONCLUSIONS: The comparison carried out in the present study can provide an
      excellent means of checking the quality and accuracy of the three measurement
      techniques because they each approach the problem from a different viewpoint.
      Together the three complimentary techniques provide a well-balanced assessment of
      the drug-use situation in a given community and identify areas where more
      research is needed.

PMID- 23144260
TI  - Partial sick leave associated with disability pension: propensity score approach
      in a register-based cohort study.
AB  - OBJECTIVES: To support sustainability of the welfare society enhanced work
      retention is needed among those with impaired work ability. Partial health
      related benefits have been introduced for this target. The aim was to estimate
      the effects of partial sick leave on transition to disability pension applying
      propensity score methods. DESIGN: Register-based cohort study. SETTING: Sample
      from the national sickness insurance registers representative of the Finnish
      working population (full-time workers) with long-term sickness absence due to
      musculoskeletal disorders, mental disorders, traumas or tumours. PARTICIPANTS:
      All recipients of partial or full sickness benefit whose sick leave period had
      ended between 1 May and 31 December 2007 were included. The sample was limited to
      four most prevalent diagnostic groups-mental and musculoskeletal disorders,
      traumas and tumours. The total sample consisted of 1047 subjects on partial sick
      leave (treatment group) and 28 380 subjects on full sick leave (control group). A
      subsample (1017 and 25 249 subjects, respectively) was formed to improve the
      comparability of the two groups. OUTCOME MEASURES: A three-category measure and a
      binary measure for the occurrence of disability pension on the last day of 2008
      were computed. RESULTS: Partial sickness benefit reduced the risk (change in
      absolute risk) of full disability pension by 6% and increased the risk of partial
      disability pension by 8% compared with full sick leave. The effects did not
      differ markedly for the two main diagnostic groups of musculoskeletal and mental
      disorders. In men, the use of full disability pension was reduced by 10% with a
      5% increase in the use of partial disability pension, while in women the effects
      were close to those of the total sample. CONCLUSIONS: Our findings suggest that
      combining work with partial sick leave may provide one means to increase work
      retention at population level. The use of partial sick leave could be encouraged
      among men.

PMID- 23144261
TI  - Health effects following the Eyjafjallajokull volcanic eruption: a cohort study.
AB  - OBJECTIVES: The study aimed to determine whether exposure to a volcanic eruption
      was associated with increased prevalence of physical and/or mental symptoms.
      DESIGN: Cohort, with non-exposed control group. SETTING: Natural disasters like
      volcanic eruptions constitute a major public-health threat. The Icelandic volcano
      Eyjafjallajokull exposed residents in southern Iceland to continuous ash fall for
      more than 5 weeks in spring 2010. This study was conducted during November 2010
      March 2011, 6-9 months after the Eyjafjallajokull eruption. PARTICIPANTS: Adult
      (18-80 years of age) eruption-exposed South Icelanders (N=1148) and a control
      population of residents of Skagafjordur, North Iceland (N=510). The participation
      rate was 72%. MAIN OUTCOME MEASURES: Physical symptoms in the previous year
      (chronic), in the previous month (recent), General Health Questionnaire (GHQ-12)
      measured psychological morbidity. RESULTS: The likelihood of having symptoms
      during the last month was higher in the exposed population, such as; tightness in
      the chest (OR 2.5; 95% CI 1.1 to 5.8), cough (OR 2.6; 95% CI 1.7 to 3.9), phlegm
      (OR 2.1; 95% CI 1.3 to 3.2), eye irritation (OR 2.9; 95% CI 2.0 to 4.1) and
      psychological morbidity symptoms (OR 1.3; 95% CI 1.0 to 1.7). Respiratory
      symptoms during the last 12 months were also more common in the exposed
      population; cough (OR 2.2; 95% CI 1.6 to 2.9), dyspnoea (OR 1.6; 95% CI 1.1 to
      2.3), although the prevalence of underlying asthma and heart disease was similar.
      Twice as many in the exposed population had two or more symptoms from nose, eyes
      or upper-respiratory tract (24% vs 13%, p<0.001); these individuals were also
      more likely to experience psychological morbidity (OR 4.7; 95% CI 3.4 to 6.5)
      compared with individuals with no symptoms. Most symptoms exhibited a dose
      response pattern within the exposed population, corresponding to low, medium and
      high exposure to the eruption. CONCLUSIONS: 6-9 months after the Eyjafjallajokull
      eruption, residents living in the exposed area, particularly those closest to the
      volcano, had markedly increased prevalence of various physical symptoms. A
      portion of the exposed population reported multiple symptoms and may be at risk
      for long-term physical and psychological morbidity. Studies of long-term
      consequences are therefore warranted.

PMID- 23144262
TI  - The welfare burden of adolescent anxiety and depression: a prospective study of
      7500 young Norwegians and their families: the HUNT study.
AB  - OBJECTIVES: To examine the association between anxiety and depression symptoms in
      adolescents and their families and later medical benefit receipt in young
      adulthood. DESIGN: Prospective cohort study. Norwegian population study linked to
      national registers. PARTICIPANTS: Data from the Nord-Trondelag Health Study 1995
      1997 (HUNT) gave information on anxiety and depression symptoms as self-reported
      by 7497 school-attending adolescents (Hopkins Symptoms Checklist-SCL-5 score) and
      their parents (Hospital Anxiety and Depression Scale score). There were 2711
      adolescents with one or more siblings in the cohort. OUTCOME MEASURES:
      Adolescents were followed for 10 years in national social security registers,
      identifying long-term receipt of medical benefits (main outcome) and unemployment
      benefits for comparison from ages 20-29. METHODS: We used logistic regression to
      estimate OR of benefit receipt for groups according to adolescent and parental
      anxiety and depression symptom load (high vs low symptom loads) and for a one
      point increase in the continuous SCL-5 score (range 1-4). We adjusted for family
      level confounders by comparing siblings differentially exposed to anxiety and
      depression symptoms. RESULTS: Comparing siblings, a one point increase in the
      mean SCL-5 score was associated with a 65% increase in the odds of medical
      benefit receipt from age 20-29 (adjusted OR, 1.65, 95% CI 1.10 to 2.48). Parental
      anxiety and depression symptom load was an indicator of their adolescent's future
      risk of medical benefit receipt, and adolescents with both parents reporting high
      symptom loads seemed to be at a particularly high risk. The anxiety and
      depression symptom load was only weakly associated with unemployment benefits.
      CONCLUSIONS: Adolescents in families hampered by anxiety and depression symptoms
      are at a substantially higher risk of medical welfare dependence in young
      adulthood. The prevention and treatment of anxiety and depression in adolescence
      should be family-oriented and aimed at ensuring work-life integration.

PMID- 23144263
TI  - Long-term impact of pregnancy-related venous thrombosis on quality-of-life,
      general health and functioning: results of a cross-sectional, case-control study.
AB  - OBJECTIVES: To evaluate the long-term consequences of pregnancy-related venous
      thrombosis (VT) by the assessment of generic quality-of-life (QOL), well-being,
      general health and daily-life functioning. We also wanted to evaluate the impact
      of the frequently occurring complication post-thrombotic syndrome (PTS) after
      that of deep vein thrombosis (DVT). DESIGN: Population-based cross-sectional,
      case-control study. SETTING: 18 Norwegian hospitals during 1990-2003.
      PARTICIPANTS: The study population comprised 559 cases with a validated first
      ever, pregnancy-related VT and 1229 controls naive for VT at the time of index
      pregnancy. Cases were identified using the Norwegian Patient Register and the
      Medical Birth Registry of Norway and the latter was used to select as controls
      women who gave birth at the same time as a case. After exclusion of two cases
      with missing location of VT, the final study population comprised 311 cases and
      353 controls. METHODS: Self-completion of a comprehensive questionnaire in 2006.
      MAIN OUTCOME MEASURES: Generic QOL and well-being assessed by the Ferrans and
      Powers QOL Index (QLI) and the General Health Questionnaire (GHQ-20). RESULTS:
      QOL assessed by QLI did not differ between cases and controls; mean score 23.1
      (95% CI 22.7 to 23.5) vs 23.7 (23.3 to 24.0), neither did well being assessed by
      GHQ-20; 18.7 (18.0 to 19.4) vs 17.9 (17.3 to 18.4). However, cases reported pain
      other than in the lower limbs and muscle-skeletal problems more often and were
      more often physically worn out after work compared with controls. Cases which
      developed PTS reported poorer health, had pain more often, developed skin and
      psychiatric problems, used analgesic drugs more frequently and were more often on
      sick leave as compared to those without PTS. CONCLUSIONS: Long-term generic QOL
      and subjective well-being 3-16 years after a pregnancy-related VT were not
      different from a reference population, but women with PTS after DVT seemed to
      have poorer QOL and an impaired general health.

PMID- 23144264
TI  - Addressing the interface of the political and commercial determinants of health.

PMID- 23144266
TI  - Introduction.

PMID- 23144276
TI  - The formative years of the British Geriatrics Society.

PMID- 23144282
TI  - Age and Ageing at 40: personal perspective Cameron G. Swift.

PMID- 23144265
TI  - Interhemispheric temporal lobe connectivity predicts language impairment in
      adolescents born preterm.
AB  - Although language difficulties are common in children born prematurely, robust
      neuroanatomical correlates of these impairments remain to be established. This
      study investigated whether the greater prevalence of language problems in preterm
      (versus term-born) children might reflect injury to major intra- or
      interhemispheric white matter pathways connecting frontal and temporal language
      regions. To investigate this, we performed a comprehensive assessment of language
      and academic abilities in a group of adolescents born prematurely, some of whom
      had evidence of brain injury at birth (n = 50, mean age: 16 years, mean
      gestational age: 27 weeks) and compared them to a term-born control group (n =
      30). Detailed structural magnetic resonance imaging and diffusion-tractography
      analyses of intrahemispheric and interhemispheric white matter bundles were
      performed. Analysis of intrahemispheric pathways included the arcuate fasciculus
      (dorsal language pathway) and uncinate fasciculus/extreme capsule (ventral
      language pathway). Analysis of interhemispheric pathways (in particular,
      connections between the temporal lobes) included the two major commissural
      bundles: the corpus callosum and anterior commissure. We found language
      impairment in 38% of adolescents born preterm. Language impairment was not
      related to abnormalities of the arcuate fasciculus (or its subsegments), but was
      associated with bilateral volume reductions in the ventral language pathway.
      However, the most significant volume reduction was detected in the posterior
      corpus callosum (splenium), which contains interhemispheric connections between
      the occipital, parietal and temporal lobes. Diffusion tractography showed that of
      the three groups of interhemispheric fibres within the splenium, only those
      connecting the temporal lobes were reduced. Crucially, we found that language
      impairment was only detectable if the anterior commissure (a second temporal lobe
      commissural pathway) was also small. Regression analyses showed that a
      combination of anatomical measures of temporal interhemispheric connectivity
      (through the splenium of the corpus callosum and anterior commissure) explained
      57% of the variance in language abilities. This supports recent theories
      emphasizing the importance of interhemispheric connections for language,
      particularly in the developing brain.

PMID- 23144285
TI  - Where the journal is today.

PMID- 23144286
TI  - Evaluation of a mental test score for assessment of mental impairment in the
      elderly. 1972.

PMID- 23144287
TI  - The clock-drawing test. 1998.

PMID- 23144288
TI  - Biography of Prof. Norman Exton-Smith, Editor 1972-1985.

PMID- 23144292
TI  - Serum gamma-glutamyltransferase and the risk of heart failure in men and women in
      Finland.
AB  - OBJECTIVES: To evaluate the association of serum gamma-glutamyltransferase (GGT)
      levels with heart failure (HF) risk in the Finnish population. DESIGN:
      Prospective population-based cohort study. SETTING: The present study, which is a
      part of FINRISK study, was carried out in Finland. Subject study cohorts included
      18 353 Finnish men and 19 726 women who were 25-74 years of age and free of HF at
      baseline. Main outcome measures HF (636 men and 445 women) during a mean follow
      up of 14.5 years. RESULTS: Baseline measurement of different levels of serum GGT
      was used to predict incident HF. The multivariable-adjusted (age, sex, study
      area, study year, smoking, education, alcohol consumption, physical activity,
      valvular heart disease, body mass index (BMI), systolic blood pressure, total
      cholesterol at baseline, myocardial infarction and diabetes at baseline and
      during follow-up) HRs of HF at five GGT groups (using the 25th, 50th, 75th and
      90th percentiles) were 1.00, 1.16 (95% CI: 0.97 to 1.38), 1.20 (1.00 to 1.45),
      1.29 (1.04 to 1.60) and 1.82 (1.45 to 2.29) (P(trend)<0.001). Stratification by
      smoking status, alcohol consumption and BMI gave similar results, while stronger
      association was observed among subjects aged <60 years (P(trend)=0.001) compared
      with subjects 60+ years of age (P(trend)=0.173). CONCLUSIONS: Moderate to high
      levels of serum GGT (from the 50th to the 90th percentiles) were significantly
      associated with incident HF in men and women in Finland, and the predictive power
      was stronger in subjects aged <60 years.

PMID- 23144293
TI  - The kynurenine pathway in brain tumor pathogenesis.
AB  - Brain tumors are among the most common and most chemoresistant tumors. Despite
      treatment with aggressive treatment strategies, the prognosis for patients
      harboring malignant gliomas remains dismal. The kynurenine pathway (KP) is the
      principal route of L-tryptophan catabolism leading to the formation of the
      essential pyridine nucleotide, nicotinamide adenine dinucleotide (NAD(+)), and
      important neuroactive metabolites, including the neurotoxin, quinolinic acid
      (QUIN), the neuroprotective agent, picolinic acid (PIC), the T(H)17/Treg balance
      modulator, 3-hydroxyanthranilic acid (3-HAA), and the immunosuppressive agent, L
      kynurenine (KYN). This review provides a new perspective on KP dysregulation in
      defeating antitumor immune responses, specifically bringing light to the lower
      segment of the KP, particularly QUIN-induced neurotoxicity and downregulation of
      the enzyme alpha-amino-beta-carboxymuconate-epsilon-semialdehyde decarboxylase
      (ACMSD) as a potential mechanism of tumor progression. Given its
      immunosuppressive effects, 3-HAA produced from the KP may also play a role in
      suppressing antitumor immunity in human tumors. The enzyme indoleamine 2, 3
      dioxygenase (IDO-1) initiates and regulates the first step of the KP in most
      cells. Mounting evidence directly implicates that the induction and
      overexpression of IDO-1 in various tumors is a crucial mechanism facilitating
      tumor immune evasion and persistence. Tryptophan 2, 3-dioxygenase (TDO-2), which
      initiates the same first step of the KP as IDO-1, has likewise recently been
      shown to be a mechanism of tumoral immune resistance. Further, it was also
      recently shown that TDO-2-dependent production of KYN by brain tumors might be a
      novel mechanism for suppressing antitumor immunity and supporting tumor growth
      through the activation of the Aryl hydrocarbon receptor (AhR). This newly
      identified TDO-2-KYN-AhR signaling pathway opens up exciting future research
      opportunities and may represent a novel therapeutic target in cancer therapy. Our
      discussion points to a number of KP components, namely TDO-2, IDO-1, and ACMSD,
      as important therapeutic targets for the treatment of brain cancer. Targeting the
      KP in brain tumors may represent a viable strategy likely to prevent QUIN-induced
      neurotoxicity and KYN and 3-HAA-mediated immune suppression.

PMID- 23144296
TI  - The challenges and principles of teaching clinical neuroscience.

PMID- 23144294
TI  - Polo-like kinase 1: a potential therapeutic option in combination with
      conventional chemotherapy for the management of patients with triple-negative
      breast cancer.
AB  - Breast cancers are composed of molecularly distinct subtypes with different
      clinical outcomes and responses to therapy. To discover potential therapeutic
      targets for the poor prognosis-associated triple-negative breast cancer (TNBC),
      gene expression profiling was carried out on a cohort of 130 breast cancer
      samples. Polo-like kinase 1 (PLK1) was found to be significantly overexpressed in
      TNBC compared with the other breast cancer subtypes. High PLK1 expression was
      confirmed by reverse phase protein and tissue microarrays. In triple-negative
      cell lines, RNAi-mediated PLK1 depletion or inhibition of PLK1 activity with a
      small molecule (BI-2536) induced an increase in phosphorylated H2AX, G(2)-M
      arrest, and apoptosis. A soft-agar colony assay showed that PLK1 silencing
      impaired clonogenic potential of TNBC cell lines. When cells were grown in
      extracellular matrix gels (Matrigel), and exposed to BI-2536, apoptosis was
      observed specifically in TNBC cancerous cells, and not in a normal cell line.
      When administrated as a single agent, the PLK1 inhibitor significantly impaired
      tumor growth in vivo in two xenografts models established from biopsies of
      patients with TNBC. Most importantly, the administration of BI-2536, in
      combination with doxorubicin + cyclophosphamide chemotherapy, led to a faster
      complete response compared with the chemotherapy treatment alone and prevented
      relapse, which is the major risk associated with TNBC. Altogether, our
      observations suggest PLK1 inhibition as an attractive therapeutic approach, in
      association with conventional chemotherapy, for the management of patients with
      TNBC.

PMID- 23144297
TI  - Higher visual function: hats, wives and disconnections.

PMID- 23144298
TI  - Alzheimer's disease: mimics and chameleons.

PMID- 23144299
TI  - Normal anatomy of the spinal cord.

PMID- 23144300
TI  - A case of acute neurogenic weakness mimicking the axonal variant of the Guillain
      Barre syndrome.

PMID- 23144301
TI  - Teaching in a busy clinic.

PMID- 23144302
TI  - Sudden proximal paraparesis secondary to statin myositis.

PMID- 23144303
TI  - Shot in the foot.

PMID- 23144304
TI  - Cerebral vasospasm and anterior circulation stroke secondary to an exacerbation
      of hereditary corproporphyria.
AB  - Acute porphyria, though rare, has well-known neurological sequelae. Vasospasm
      rarely complicates exacerbations of acute intermittent porphyria, but has not
      been previously reported in hereditary coproporphyria. We describe a porphyric
      crisis in a woman with previously undiagnosed hereditary coproporphyria
      (triggered by rifampicin), leading to vasospasm and stroke.

PMID- 23144305
TI  - Transient aqueductal occlusion in intracerebral haemorrhage.

PMID- 23144306
TI  - Aberrant regeneration of the third nerve (oculomotor synkinesis).
AB  - Aberrant regeneration of a third nerve palsy (oculomotor synkinesis) excludes an
      ischaemic cause and in the absence of relevant trauma strongly suggests a
      compressive aetiology. A scan is mandatory in such cases. We describe the case of
      a 52-year-old woman who presented with complete pupil-involving third nerve palsy
      from a posterior communicating artery aneurysm, who later developed widespread
      aberrant regeneration of pupil, eyelid and third nerve territory rectus muscles.

PMID- 23144307
TI  - Letter from Antarctica.

PMID- 23144308
TI  - A massage from Queen Square.

PMID- 23144309
TI  - Motor neurone disease is a clinical diagnosis.

PMID- 23144310
TI  - Why the curious incident of the dog in the night was 'contributory'.

PMID- 23144311
TI  - Fisher's rules: learning from the master himself.

PMID- 23144312
TI  - Macrophage migration inhibitory factor antagonizes pressure overload-induced
      cardiac hypertrophy.
AB  - Macrophage migration inhibitory factor (MIF) functions as a proinflammatory
      cytokine when secreted from the cell, but it also exhibits antioxidant properties
      by virtue of its intrinsic oxidoreductase activity. Since increased production of
      ROS is implicated in the development of left ventricular hypertrophy, we
      hypothesized that the redox activity of MIF protects the myocardium when exposed
      to hemodynamic stress. In a mouse model of myocardial hypertrophy induced by
      transverse aortic coarctation (TAC) for 10 days, we showed that growth of the MIF
      deficient heart was significantly greater by 32% compared with wild-type (WT) TAC
      hearts and that fibrosis was increased by fourfold (2.62 +/- 0.2% vs. 0.6 +/-
      0.1%). Circulating MIF was increased in TAC animals, and expression of MIF
      receptor, CD74, was increased in the hypertrophic myocardium. Gene expression
      analysis showed a 10-fold increase (P < 0.01) in ROS-generating mitochondrial
      NADPH oxidase and 2- to 3-fold reductions (P < 0.01) in mitochondrial SOD2 and
      mitochondrial aconitase activities, indicating enhanced oxidative injury in the
      hypertrophied MIF-deficient ventricle. Hypertrophic signaling pathways showed
      that phosphorylation of cytosolic glycogen synthase kinase-3alpha was greater (P
      < 0.05) at baseline in MIF-deficient hearts than in WT hearts and remained
      elevated after 10-day TAC. In the hemodynamically stressed MIF-deficient heart,
      nuclear p21(CIP1) increased sevenfold (P < 0.01), and the cytosolic increase of
      phospho-p21(CIP1) was significantly greater than in WT TAC hearts. We conclude
      that MIF antagonizes myocardial hypertrophy and fibrosis in response to
      hemodynamic stress by maintaining a redox homeostatic phenotype and attenuating
      stress-induced activation of hypertrophic signaling pathways.

PMID- 23144313
TI  - (-)-Epicatechin administration and exercising skeletal muscle vascular control
      and microvascular oxygenation in healthy rats.
AB  - Consumption of the dietary flavanol (-)-epicatechin (EPI) is associated with
      enhanced endothelial function and augmented skeletal muscle capillarity and
      mitochondrial volume density. The potential for EPI to improve peripheral
      vascular function and muscle oxygenation during exercise is unknown. We tested
      the hypothesis that EPI administration in healthy rats would improve treadmill
      exercise performance secondary to elevated skeletal muscle blood flow and
      vascular conductance [VC, blood flow/mean arterial pressure (MAP)] and improved
      skeletal muscle microvascular oxygenation. Rats received water (control, n = 12)
      or 4 mg/kg EPI (n = 12) via oral gavage daily for 24 days. Exercise endurance
      capacity and peak O(2) uptake (Vo(2) peak) were measured via treadmill runs to
      exhaustion. MAP (arterial catheter) and blood flow (radiolabeled microspheres)
      were measured and VC was calculated during submaximal treadmill exercise (25
      m/min, 5% grade). Spinotrapezius muscle microvascular O(2) pressure (Po(2mv)) was
      measured (phosphorescence quenching) during electrically induced twitch (1 Hz)
      contractions. In conscious rats, EPI administration resulted in lower (?~5%)
      resting (P = 0.03) and exercising (P = 0.04) MAP. There were no differences in
      exercise endurance capacity, Vo(2) peak, total exercising hindlimb blood flow
      (control, 154 +/- 13; and EPI, 159 +/- 8 ml.min(-1).100 g(-1), P = 0.68), or VC
      (control, 1.13 +/- 0.10; and EPI, 1.24 +/- 0.08 ml.min(-1).100 g(-1).mmHg(-1), P
      = 0.21) between groups. Following anesthesia, EPI resulted in lower MAP (?~16%)
      but did not impact resting Po(2mv) or any kinetics parameters (P > 0.05 for all)
      during muscle contractions compared with control. EPI administration (4 mg.kg(
      1).day(-1)) improved modestly cardiovascular function (i.e., ?MAP) with no impact
      on exercise performance, total exercising skeletal muscle blood flow and VC, or
      contracting muscle microvascular oxygenation in healthy rats.

PMID- 23144314
TI  - Deletion of 1-43 amino acids in cardiac myosin essential light chain blunts
      length dependency of Ca(2+) sensitivity and cross-bridge detachment kinetics.
AB  - The role of cardiac myosin essential light chain (ELC) in the sarcomere length
      (SL) dependency of myofilament contractility is unknown. Therefore, mechanical
      and dynamic contractile properties were measured at SL 1.9 and 2.2 MUm in cardiac
      muscle fibers from two groups of transgenic (Tg) mice: 1) Tg-wild-type (WT) mice
      that expressed WT human ventricular ELC and 2) Tg-Delta43 mice that expressed a
      mutant ELC lacking 1-43 amino acids. In agreement with previous studies, Ca(2+)
      activated maximal tension decreased significantly in Tg-Delta43 fibers. pCa(50) (
      log(10) [Ca(2+)](free) required for half maximal activation) values at SL of 1.9
      MUm were 5.64 +/- 0.02 and 5.70 +/- 0.02 in Tg-WT and Tg-Delta43 fibers,
      respectively. pCa(50) values at SL of 2.2 MUm were 5.70 +/- 0.01 and 5.71 +/-
      0.01 in Tg-WT and Tg-Delta43 fibers, respectively. The SL-mediated increase in
      the pCa(50) value was statistically significant only in Tg-WT fibers (P < 0.01),
      indicating that the SL dependency of myofilament Ca(2+) sensitivity was blunted
      in Tg-Delta43 fibers. The SL dependency of cross-bridge (XB) detachment kinetics
      was also blunted in Tg-Delta43 fibers because the decrease in XB detachment
      kinetics was significant (P < 0.001) only at SL 1.9 MUm. Thus the increased XB
      dwell time at the short SL augments Ca(2+) sensitivity at short SL and thus
      blunts SL-mediated increase in myofilament Ca(2+) sensitivity. Our data suggest
      that the NH(2)-terminal extension of cardiac ELC not only augments the amplitude
      of force generation, but it also may play a role in mediating the SL dependency
      of XB detachment kinetics and myofilament Ca(2+) sensitivity.

PMID- 23144315
TI  - Impact of site-specific phosphorylation of protein kinase A sites Ser23 and Ser24
      of cardiac troponin I in human cardiomyocytes.
AB  - PKA-mediated phosphorylation of contractile proteins upon beta-adrenergic
      stimulation plays an important role in the regulation of cardiac performance.
      Phosphorylation of the PKA sites (Ser(23)/Ser(24)) of cardiac troponin (cTn)I
      results in a decrease in myofilament Ca(2+) sensitivity and an increase in the
      rate of relaxation. However, the relation between the level of phosphorylation of
      the sites and the functional effects in the human myocardium is unknown.
      Therefore, site-directed mutagenesis was used to study the effects of
      phosphorylation at Ser(23) and Ser(24) of cTnI on myofilament function in human
      cardiac tissue. Serines were replaced by aspartic acid (D) or alanine (A) to
      mimic phosphorylation and dephosphorylation, respectively. cTnI-DD mimics both
      sites phosphorylated, cTnI-AD mimics Ser(23) unphosphorylated and Ser(24)
      phosphorylated, cTnI-DA mimics Ser(23) phosphorylated and Ser(24)
      unphosphorylated, and cTnI-AA mimics both sites unphosphorylated. Force
      development was measured at various Ca(2+) concentrations in permeabilized
      cardiomyocytes in which the endogenous troponin complex was exchanged with these
      recombinant human troponin complexes. In donor cardiomyocytes, myofilament Ca(2+)
      sensitivity (pCa(50)) was significantly lower in cTnI-DD (pCa(50): 5.39 +/- 0.01)
      compared with cTnI-AA (pCa(50): 5.50 +/- 0.01), cTnI-AD (pCa(50): 5.48 +/- 0.01),
      and cTnI-DA (pCa(50): 5.51 +/- 0.01) at ~70% cTn exchange. No effects were
      observed on the rate of tension redevelopment. In cardiomyocytes from idiopathic
      dilated cardiomyopathic tissue, a linear decline in pCa(50) with cTnI-DD content
      was observed, saturating at ~55% bisphosphorylation. Our data suggest that in the
      human myocardium, phosphorylation of both PKA sites on cTnI is required to reduce
      myofilament Ca(2+) sensitivity, which is maximal at ~55% bisphosphorylated cTnI.
      The implications for in vivo cardiac function in health and disease are detailed
      in the DISCUSSION in this article.

PMID- 23144317
TI  - Fragmented care: a practicing surgeon's response.

PMID- 23144316
TI  - Identification of a region of rat chromosome 1 that impairs the myogenic response
      and autoregulation of cerebral blood flow in fawn-hooded hypertensive rats.
AB  - This study examined the effects of transfer of a 2.4-Mbp region of rat chromosome
      1 (RNO1) from Brown Norway (BN) into fawn-hooded hypertensive (FHH) rats on
      autoregulation (AR) of cerebral blood flow (CBF) and the myogenic response of
      middle cerebral arteries (MCAs). AR of CBF was poor in FHH and FHH.1(BN) AR(-)
      congenic strains that excluded the critical 2.4-Mbp region. In contrast, AR was
      restored in FHH.1(BN) AR(+) congenic strains that included this region. The
      diameter of MCAs of FHH rats increased from 140 +/- 14 to 157 +/- 18 MUm when
      transmural pressure was increased from 40 to 140 mmHg, but it decreased from 137
      +/- 5 to 94 +/- 7 MUm in FHH.1(BN) AR(+) congenic strains. Transient occlusion of
      MCAs reduced CBF by 80% in all strains. However, the hyperemic response following
      ischemia was significantly greater in FHH and AR(-) rats than that seen in AR(+)
      congenic strains (AR(-), 173 +/- 11% vs. AR(+), 124 +/- 5%). Infarct size and
      edema formation were also significantly greater in an AR(-) strain (38.6 +/- 2.6
      and 12.1 +/- 2%) than in AR(+) congenic strains (27.6 +/- 1.8 and 6.5 +/- 0.9%).
      These results indicate that there is a gene in the 2.4-Mbp region of RNO1 that
      alters the development of myogenic tone in cerebral arteries. Transfer of this
      region from BN to FHH rats restores AR of CBF and vascular reactivity and reduces
      cerebral injury after transient occlusion and reperfusion of the MCA.

PMID- 23144319
TI  - Prognostic implications of genetic variants in advanced non-small cell lung
      cancer: a genome-wide association study.
AB  - The prognostic significance of inherited genetic variants in advanced-stage non
      small cell lung cancer (NSCLC) patients remains unknown. In this study, we
      genotyped 271 817 single-nucleotide polymorphisms in 348 advanced NSCLC patients
      who received chemotherapy and analyzed their association with prognosis by using
      Cox proportional hazard regression model adjusted for known prognostic factors.
      Top candidate single-nucleotide polymorphisms (SNPs) were selected using the
      bootstrap re-sampling procedure. Median age of patient population was 56 years.
      Proportions of female, never smokers and adenocarcinoma were 64.9, 67.5 and
      80.4%, respectively. We identified 17 top candidate SNPs related to prognosis
      using cut-off minimum P value of <5.0 * 10(-5) in at least 70% of 1000 bootstrap
      samples. These SNPs were located in the genomic regions of the FAM154A, ANKS1A,
      DLST, THSD7B, NCOA2, CDH8, SLC35D2, NALCN and EGF genes. The most significant
      SNP, rs1571228 (9p22.1:FAM154A), was significantly associated with overall
      survival in dominant model [AG+GG to AA, hazard ratio (HR) of death (95% CI) =
      0.53 (0.42-0.67); P = 2.025 * 10(-7)]. The SNP at 4q25:EGF, rs11098063, for which
      some genetic variations was previously reported to be associated with prognosis,
      also showed significant association with overall survival in additive model [CC
      versus CT versus TT, HR (95% CI) = 1.00 versus 0.61 (0.47-0.78) versus 0.39 (0.19
      0.79); P = 9.582 * 10(-6)]. Survival differences according to the genotype of
      these SNPs were independent of sex, smoking, histology and chemotherapy regimens.
      These results suggested the variants at multiple genetic loci might contribute to
      the risk of death in advanced NSCLC patients receiving chemotherapy.

PMID- 23144320
TI  - Retroperitoneal malignant nerve sheath tumor.

PMID- 23144318
TI  - Suppression of Wnt1-induced mammary tumor growth and lower serum insulin in
      offspring exposed to maternal blueberry diet suggest early dietary influence on
      developmental programming.
AB  - Despite the well-accepted notion that early maternal influences persist beyond
      fetal life and may underlie many adult diseases, the risks imposed by the
      maternal environment on breast cancer development and underlying biological
      mechanisms remain poorly understood. In this study, we investigated whether early
      exposure to blueberry (BB) via maternal diet alters oncogene Wnt1-induced mammary
      tumorigenesis in offspring. Wnt1-transgenic female mice were exposed to maternal
      Casein (CAS, control) or blueberry-supplemented (CAS + 3%BB) diets throughout
      pregnancy and lactation. Offspring were weaned to CAS and mammary tumor
      development was followed until age 8 months. Tumor incidence and latency were
      similar for both groups; however, tumor weight at killing and tumor volume within
      2 weeks of initial detection were lower (by 50 and 60%, respectively) in
      offspring of BB- versus control-fed dams. Dietary BB exposure beginning at
      weaning did not alter mammary tumor parameters. Tumors from maternal BB-exposed
      offspring showed higher tumor suppressor (Pten and Cdh1) and lower
      proproliferative (Ccnd1), anti-apoptotic (Bcl2) and proangiogenic (Figf, Flt1 and
      Ephb4) transcript levels, and displayed attenuated microvessel density.
      Expression of Pten and Cdh1 genes was also higher in mammary tissues of maternal
      BB-exposed offspring. Mammary tissues and tumors of maternal BB-exposed offspring
      showed increased chromatin-modifying enzyme Dnmt1 and Ezh2 transcript levels.
      Body weight, serum insulin and serum leptin/adiponectin ratio were lower for
      maternal BB-exposed than control tumor-bearing offspring. Tumor weights and serum
      insulin were positively correlated. Results suggest that dietary influences on
      the maternal environment contribute to key developmental programs in the mammary
      gland to modify breast cancer outcome in adult progeny.

PMID- 23144321
TI  - Accelerated structural decrements in the aging female rhesus macaque lung
      compared with males.
AB  - Aging is associated with morphometric changes in the lung that lead to decreased
      lung function. The nonhuman primate lung has been shown to have similar
      architectural, morphological, and developmental patterns to that of humans. We
      hypothesized that the lungs of rhesus monkeys age in a pattern similar to human
      lungs. Thirty-four rhesus monkeys from the California National Primate Research
      Center were euthanized, necropsied, and the whole lungs sampled. Stereological
      analysis was performed to assess the morphological changes associated with age.
      The number of alveoli declined significantly from age 9 to 33 yr with a greater
      decline in females compared with males. Lungs of females contained roughly 20%
      more alveoli at age 9 yr than males, but by ~30 yr of age, females had 30% fewer
      alveoli than males. The volume of alveolar air also showed a significant linear
      decrease in females relative to age, while males did not. The number-weighted
      mean volume of alveoli showed a significant positive correlation with age in
      females but not in males. The volume of alveolar duct showed a significant
      positive correlation with age in females, but not in males. Structural decrements
      due to aging in the lung were increased in the female compared with male rhesus
      monkey.

PMID- 23144322
TI  - Wnt5a inhibits hypoxia-induced pulmonary arterial smooth muscle cell
      proliferation by downregulation of beta-catenin.
AB  - Chronic hypoxia-induced pulmonary arterial hypertension (HPH) is closely
      associated with profound vascular remodeling, especially pulmonary arterial
      medial hypertrophy and muscularization due to hyperplasia of pulmonary artery
      smooth muscle cells (PASMCs). Aberrant Wnt signaling has been associated with
      lung diseases, but its role in pulmonary hypertension is unclear. This study
      evaluated the effect of Wnt5a on hypoxia-induced proliferation of human PASMCs
      and its possible mechanism. The results show that hypoxia (3% O(2), 48 h) induced
      proliferation of human PASMCs, accompanied with a significant decrease in Wnt5a
      gene expression, increase in beta-catenin and Cyclin D1 expression, as well as
      beta-catenin nuclear translocation. Treatment with recombinant mouse Wnt5a
      significantly inhibited hypoxia-induced proliferation of human PASMCs,
      upregulation of Cyclin D1 and beta-catenin expression, as well as the nuclear
      translocation of beta-catenin. These effects were inhibited by Wnt5a antibody.
      Knocking down beta-catenin or Cyclin D1 gene expression inhibited hypoxia-induced
      human PASMC proliferation, whereas overexpression of beta-catenin increased
      hypoxia-induced human PASMC proliferation and counteracted the inhibitory effect
      of Wnt5a. These results suggest that Wnt5a has an antiproliferative effect on
      hypoxia-induced human PASMC proliferation by downregulation of beta-catenin and
      its target gene Cyclin D1. Hypoxia-induced downregulation of Wnt5a may be a way
      to facilitate hypoxia-induced human PASMC proliferation. The results of this
      study will help to understand the novel strategies for PH treatment involving Wnt
      signaling.

PMID- 23144323
TI  - Human airway ciliary dynamics.
AB  - Airway cilia depend on precise changes in shape to transport the mucus gel
      overlying mucosal surfaces. The ciliary motion can be recorded in several planes
      using video microscopy. However, cilia are densely packed, and automated
      computerized systems are not available to convert these ciliary shape changes
      into forms that are useful for testing theoretical models of ciliary function. We
      developed a system for converting planar ciliary motions recorded by video
      microscopy into an empirical quantitative model, which is easy to use in
      validating mathematical models, or in examining ciliary function, e.g., in
      primary ciliary dyskinesia (PCD). The system we developed allows the manipulation
      of a model cilium superimposed over a video of beating cilia. Data were analyzed
      to determine shear angles and velocity vectors of points along the cilium.
      Extracted waveforms were used to construct a composite waveform, which could be
      used as a standard. Variability was measured as the mean difference in position
      of points on individual waveforms and the standard. The shapes analyzed were the
      end-recovery, end-effective, and fastest moving effective and recovery with mean
      (+/- SE) differences of 0.31(0.04), 0.25(0.06), 0.50(0.12), 0.50(0.10), MUm,
      respectively. In contrast, the same measures for three different PCD waveforms
      had values far outside this range.

PMID- 23144324
TI  - Adenosine and arteriogenesis: promoter or suppressor?

PMID- 23144325
TI  - P2X7-regulated protection from exacerbations and loss of control is independent
      of asthma maintenance therapy.
AB  - RATIONALE: The function of the P2X(7) nucleotide receptor protects against
      exacerbation in people with mild-intermittent asthma during viral illnesses, but
      the impact of disease severity and maintenance therapy has not been studied.
      OBJECTIVES: To evaluate the association between P2X(7), asthma exacerbations, and
      incomplete symptom control in a more diverse population. METHODS: A matched P2RX7
      genetic case-control was performed with samples from Asthma Clinical Research
      Network trial participants enrolled before July 2006, and P2X(7) pore activity
      was determined in whole blood samples as an ancillary study to two trials
      completed subsequently. MEASUREMENTS AND MAIN RESULTS: A total of 187
      exacerbations were studied in 742 subjects, and the change in asthma symptom
      burden was studied in an additional 110 subjects during a trial of inhaled
      corticosteroids (ICS) dose optimization. African American carriers of the minor G
      allele of the rs2230911 loss-of-function single nucleotide polymorphism were more
      likely to have a history of prednisone use in the previous 12 months, with
      adjustment for ICS and long-acting beta(2)-agonists use (odds ratio, 2.7; 95%
      confidence interval, 1.2-6.2; P = 0.018). Despite medium-dose ICS, attenuated
      pore function predicted earlier exacerbations in incompletely controlled patients
      with moderate asthma (hazard ratio, 3.2; confidence interval, 1.1-9.3; P =
      0.033). After establishing control with low-dose ICS in patients with mild
      asthma, those with attenuated pore function had more asthma symptoms, rescue
      albuterol use, and FEV(1) reversal (P < 0.001, 0.03, and 0.03, respectively)
      during the ICS adjustment phase. CONCLUSIONS: P2X(7) pore function protects
      against exacerbations of asthma and loss of control, independent of baseline
      severity and the maintenance therapy.

PMID- 23144327
TI  - Neurohormonal axis in patients with pulmonary arterial hypertension: friend or
      foe?
AB  - Despite its description some 25 years ago, neurohormonal activation has long been
      neglected as an important factor in the pathophysiology of pulmonary arterial
      hypertension (PAH). Neurohormonal activation was interpreted as a necessary
      compensatory response to maintain cardiac contractility and systemic blood
      pressure. Therefore, inhibitors of neurohormonal activity (like beta-blockers or
      angiotensin-converting enzyme inhibitors) are considered contraindicated in
      current PAH management guidelines. However, recent data revealed that sympathetic
      overstimulation is strongly related to mortality, and blockade of neurohormonal
      activity in experimental PAH improved survival and cardiac function. These novel
      insights shed new light on the role of neurohormonal activity in PAH.

PMID- 23144329
TI  - Chronic obstructive pulmonary disease and lipid core carotid artery plaques in
      the elderly: the Rotterdam Study.
AB  - RATIONALE: Chronic obstructive pulmonary disease (COPD) is an independent risk
      factor for ischemic stroke and the risk increases with severity of airflow
      limitation. Even though vulnerable carotid artery plaque components, such as
      intraplaque hemorrhage and lipid core, place persons at high risk for ischemic
      events, the plaque composition in patients with COPD has never been explored.
      OBJECTIVES: To investigate the prevalence of carotid wall thickening, the
      different carotid artery plaque components, and their relationship with severity
      of airflow limitation in elderly patients with COPD. METHODS: This cross
      sectional analysis was part of the Rotterdam Study, a prospective population
      based cohort study performed in subjects aged 55 years and older. Diagnosis of
      COPD was confirmed by spirometry. Participants with carotid wall intima-media
      thickness greater than or equal to 2.5 mm on ultrasonography underwent high
      resolution magnetic resonance imaging for characterization of carotid plaques.
      Data were analyzed using logistic regression. MEASUREMENTS AND MAIN RESULTS: COPD
      cases (n = 253) had a twofold increased risk (odds ratio, 2.0; 95% confidence
      interval, 1.44-2.85; P < 0.0001) of presentation with carotid wall thickening on
      ultrasonography compared with control subjects with a normal lung function (n =
      920). Moreover, the risk increased significantly with severity of airflow
      limitation. On magnetic resonance imaging, vulnerable lipid core plaques were
      more frequent in COPD cases than in control subjects (odds ratio, 2.1; 95%
      confidence interval, 1.25-3.69; P = 0.0058). CONCLUSIONS: Carotid artery wall
      thickening is more prevalent in patients with COPD than in control subjects. In
      elderly subjects with carotid wall thickening, COPD is an independent predictor
      for the presence of a lipid core, and therefore of vulnerable plaques.

PMID- 23144330
TI  - Picking up the pieces: towards a better future for critical care medicine in
      three South American countries.
AB  - The demand for intensivists is increasing around the world, not only to meet the
      needs of a growing aging population, but also to fill positions in the intensive
      care unit now occupied by other specialists, since there is compelling evidence
      that the presence of critical care practitioners improves patient outcomes.
      Notwithstanding this, the shortage of intensivists is a problem recognized
      throughout the world. In this article, we discuss these issues in Argentina,
      Brazil, and Uruguay, three upper-middle income Latin American countries where
      critical care has been a medical specialty for decades and intensive care unit
      coverage traditionally has followed the 24/7 model. The lack of intensivists is
      multifactorial: the specialty is not taught to medical students; there is a
      general perception of a negative lifestyle compared with the practice of other
      medical specialties, due mainly to the constant 24-hour shift work; and there is
      general dissatisfaction with incomes, which has forced many intensivists into
      multijob schemes. The expected-and feared-consequences are the 40 to 70% vacant
      posts in residencies of critical care. Despite these drawbacks, scientific
      societies and colleges are intensely committed, pointing out these problems to
      the press, calling the health authorities for action, and permanently generating
      educational activities. Surprisingly, 83% of surveyed intensivists would choose
      critical care medicine again, evidencing the strong vocational component in its
      practice, which seems to predominate over negative aspects.

PMID- 23144328
TI  - Patients with nontuberculous mycobacterial lung disease exhibit unique body and
      immune phenotypes.
AB  - RATIONALE: Among patients with nontuberculous mycobacterial lung disease is a
      subset of previously healthy women with a slender body morphotype, often with
      scoliosis and/or pectus excavatum. We hypothesize that unidentified factors
      predispose these individuals to pulmonary nontuberculous mycobacterial disease.
      OBJECTIVES: To compare body morphotype, serum adipokine levels, and whole-blood
      cytokine responses of patients with pulmonary nontuberculous mycobacteria (pNTM)
      with contemporary control subjects who are well matched demographically. METHODS:
      We enrolled 103 patients with pNTM and 101 uninfected control subjects of similar
      demographics. Body mass index and body fat were quantified. All patients with
      pNTM and a subset of control subjects were evaluated for scoliosis and pectus
      excavatum. Serum leptin and adiponectin were measured. Specific cytokines
      important to host-defense against mycobacteria were measured in whole blood
      before and after stimulation. MEASUREMENTS AND MAIN RESULTS: Patients with pNTM
      and control subjects were well matched for age, gender, and race. Patients with
      pNTM had significantly lower body mass index and body fat and were significantly
      taller than control subjects. Scoliosis and pectus excavatum were significantly
      more prevalent in patients with pNTM. The normal relationships between the
      adipokines and body fat were lost in the patients with pNTM, a novel finding. IFN
      gamma and IL-10 levels were significantly suppressed in stimulated whole blood of
      patients with pNTM. CONCLUSIONS: This is the first study to comprehensively
      compare body morphotype, adipokines, and cytokine responses between patients with
      NTM lung disease and demographically matched controls. Our findings suggest a
      novel, predisposing immunophenotype that should be mechanistically defined.

PMID- 23144332
TI  - Skeletal muscle oxidative metabolism in an animal model of pulmonary emphysema:
      formoterol and skeletal muscle dysfunction.
AB  - Skeletal muscle dysfunction is a significant contributor to exercise limitation
      in pulmonary emphysema. This study investigated skeletal muscle oxidative
      metabolism before and after aerosol exposure to a long-acting beta-agonist
      (LABA), such as formoterol, in the pallid mouse (B6.Cg-Pldnpa/J), which has a
      deficiency in serum alpha(1)-antitrypsin (alpha(1)-PI) and develops spontaneous
      pulmonary emphysema. C57 BL/6J and its congener pallid mice of 8-12 and 16 months
      of age were treated with vehicle or formoterol aerosol challenge for 120 seconds.
      Morphological and morphometric studies and evaluations of mitochondrial adenosine
      diphosphate-stimulated respiration and of cytochrome oxidase activity on skeletal
      muscle were performed. Moreover, the mtDNA content in skeletal muscle and the
      mediators linked to muscle mitochondrial function and biogenesis, as well as TNF
      alpha and peroxisome proliferator-activated receptor-gamma coactivator-1alpha
      (PGC-1alpha), were also evaluated. The lungs of pallid mice at 12 and 16 months
      of age showed patchy areas of airspace enlargements, with the destruction of
      alveolar septa. No significant differences were observed in basal values of
      mitochondrial skeletal muscle oxidative processes between C57 BL/6J and pallid
      mice. Exposure to LABA significantly improved mitochondrial skeletal muscle
      oxidative processes in emphysematous mice, where the mtDNA content was
      significantly higher with respect to 8-month-old pallid mice. This effect was
      compared with a significant increase of PGC-1alpha in skeletal muscles of 16
      month-old pallid mice, with no significant changes in TNF-alpha concentrations.
      In conclusion, in emphysematous mice that showed an increased mtDNA content,
      exposure to inhaled LABA can improve mitochondrial skeletal muscle oxidative
      processes. PGC-1alpha may serve as a possible mediator of this effect.

PMID- 23144331
TI  - CXCL10-CXCR3 enhances the development of neutrophil-mediated fulminant lung
      injury of viral and nonviral origin.
AB  - RATIONALE: Patients who developed acute respiratory distress syndrome (ARDS)
      after infection with severe respiratory viruses (e.g., severe acute respiratory
      syndrome-coronavirus, H5N1 avian influenza virus), exhibited unusually high
      levels of CXCL10, which belongs to the non-ELR (glutamic-leucine-arginine) CXC
      chemokine superfamily. CXCL10 may not be a bystander to the severe virus
      infection but may directly contribute to the pathogenesis of neutrophil-mediated,
      excessive pulmonary inflammation. OBJECTIVES: We investigated the contribution of
      CXCL10 and its receptor CXCR3 axis to the pathogenesis of ARDS with nonviral and
      viral origins. METHODS: We induced nonviral ARDS by acid aspiration and viral
      ARDS by intratracheal influenza virus infection in wild-type mice and mice
      deficient in CXCL10, CXCR3, IFNAR1 (IFN-alpha/beta receptor 1), or TIR domain
      containing adaptor inducing IFN-beta (TRIF). MEASUREMENTS AND MAIN RESULTS: We
      found that the mice lacking CXCL10 or CXCR3 demonstrated improved severity and
      survival of nonviral and viral ARDS, whereas mice that lack IFNAR1 did not
      control the severity of ARDS in vivo. The increased levels of CXCL10 in lungs
      with ARDS originate to a large extent from infiltrated pulmonary neutrophils,
      which express a unique CXCR3 receptor via TRIF. CXCL10-CXCR3 acts in an autocrine
      fashion on the oxidative burst and chemotaxis in the inflamed neutrophils,
      leading to fulminant pulmonary inflammation. CONCLUSIONS: CXCL10-CXCR3 signaling
      appears to be a critical factor for the exacerbation of the pathology of ARDS.
      Thus, the CXCL10-CXCR3 axis could represent a prime therapeutic target in the
      treatment of the acute phase of ARDS of nonviral and viral origins.

PMID- 23144333
TI  - Receptor for advanced glycation end products contributes to postnatal pulmonary
      development and adult lung maintenance program in mice.
AB  - The role of the receptor for advanced glycation end products (RAGE) in promoting
      the inflammatory response through activation of NF-kappaB pathway is well
      established. Recent findings indicate that RAGE may also have a regulative
      function in apoptosis, as well as in cellular proliferation, differentiation, and
      adhesion. Unlike other organs, lung tissue in adulthood and during organ
      development shows relatively high levels of RAGE expression. Thus a role for the
      receptor in lung organogenesis and homeostasis may be proposed. To evaluate the
      role of RAGE in lung development and adult lung homeostasis, we generated
      hemizygous and homozygous transgenic mice overexpressing human RAGE, and analyzed
      their lungs from the fourth postnatal day to adulthood. Moderate RAGE
      hyperexpression during lung development influenced secondary septation, resulting
      in an impairment of alveolar morphogenesis and leading to significant changes in
      morphometric parameters such as airspace number and the size of alveolar ducts.
      An increase in alveolar cell apoptosis and a decrease in cell proliferation were
      demonstrated by the terminal deoxy-nucleotidyltransferase-mediated dUTP nick end
      labeling reaction, active caspase-3, and Ki-67 immunohistochemistry. Alterations
      in elastin organization and deposition and in TGF-beta expression were observed.
      In homozygous mice, the hyperexpression of RAGE resulted in histological changes
      resembling those changes characterizing human bronchopulmonary dysplasia (BPD).
      RAGE hyperexpression in the adult lung is associated with an increase of the
      alveolar destructive index and persistent inflammatory status leading to
      "destructive" emphysema. These results suggest an important role for RAGE in both
      alveolar development and lung homeostasis, and open new doors to working
      hypotheses on the pathogenesis of BPD and chronic obstructive pulmonary disease.

PMID- 23144326
TI  - Genome-wide association analysis of blood biomarkers in chronic obstructive
      pulmonary disease.
AB  - RATIONALE: A genome-wide association study (GWAS) for circulating chronic
      obstructive pulmonary disease (COPD) biomarkers could identify genetic
      determinants of biomarker levels and COPD susceptibility. OBJECTIVES: To identify
      genetic variants of circulating protein biomarkers and novel genetic determinants
      of COPD. METHODS: GWAS was performed for two pneumoproteins, Clara cell secretory
      protein (CC16) and surfactant protein D (SP-D), and five systemic inflammatory
      markers (C-reactive protein, fibrinogen, IL-6, IL-8, and tumor necrosis factor
      alpha) in 1,951 subjects with COPD. For genome-wide significant single nucleotide
      polymorphisms (SNPs) (P < 1 * 10(-8)), association with COPD susceptibility was
      tested in 2,939 cases with COPD and 1,380 smoking control subjects. The
      association of candidate SNPs with mRNA expression in induced sputum was also
      elucidated. MEASUREMENTS AND MAIN RESULTS: Genome-wide significant susceptibility
      loci affecting biomarker levels were found only for the two pneumoproteins. Two
      discrete loci affecting CC16, one region near the CC16 coding gene (SCGB1A1) on
      chromosome 11 and another locus approximately 25 Mb away from SCGB1A1, were
      identified, whereas multiple SNPs on chromosomes 6 and 16, in addition to SNPs
      near SFTPD, had genome-wide significant associations with SP-D levels. Several
      SNPs affecting circulating CC16 levels were significantly associated with sputum
      mRNA expression of SCGB1A1 (P = 0.009-0.03). Several SNPs highly associated with
      CC16 or SP-D levels were nominally associated with COPD in a collaborative GWAS
      (P = 0.001-0.049), although these COPD associations were not replicated in two
      additional cohorts. CONCLUSIONS: Distant genetic loci and biomarker-coding genes
      affect circulating levels of COPD-related pneumoproteins. A subset of these
      protein quantitative trait loci may influence their gene expression in the lung
      and/or COPD susceptibility. Clinical trial registered with www.clinicaltrials.gov
      (NCT 00292552).

PMID- 23144334
TI  - Metabolomics reveals altered metabolic pathways in experimental asthma.
AB  - Metabolomics refers to the comprehensive analysis of metabolites in biological
      systems, and has been employed to study patients with asthma based on their
      urinary metabolite profile. We hypothesize that airway allergic asthma would
      affect metabolism in the lungs, and could be detected in bronchoalveolar lavage
      (BAL) fluid (BALF) using a combined liquid chromatography- and gas chromatography
      mass spectrometry (MS) platform. The objective of this study was to investigate
      changes of lung metabolism in allergic asthma by metabolomic analysis of BALF.
      BALB/c mice were sensitized and challenged with ovalbumin to develop experimental
      asthma. Dexamethasone was administered to study the effects of corticosteroids on
      lung metabolism. Metabolites in BALF were measured using liquid chromatography-MS
      and gas chromatography-MS, and multivariate statistical analysis was performed by
      orthogonal projections to latent structures discriminant analysis. Metabolomic
      analysis of BALF from ovalbumin-challenged mice revealed novel changes in
      metabolic pathways in the lungs as compared with control animals. These
      metabolite changes suggest alterations of energy metabolism in asthmatic lungs,
      with increases of lactate, malate, and creatinine and reductions in
      carbohydrates, such as mannose, galactose, and arabinose. Lipid and sterol
      metabolism were affected with significant decreases in phosphatidylcholines,
      diglycerides, triglycerides, cholesterol, cortol, and cholic acid. Dexamethasone
      treatment effectively reversed many key metabolite changes, but was ineffective
      in repressing lactate, malate, and creatinine, and induced additional metabolite
      changes. Metabolomic analysis of BALF offers a promising approach to
      investigating allergic asthma. Our overall findings revealed considerable pathway
      changes in lung metabolism in asthmatic lungs, including energy, amino acids, and
      lipid metabolism.

PMID- 23144335
TI  - Modeling return on investment for an electronic medical record system in
      Lilongwe, Malawi.
AB  - OBJECTIVE: To model the financial effects of implementing a hospital-wide
      electronic medical record (EMR) system in a tertiary facility in Malawi.
      MATERIALS AND METHODS: We evaluated three areas of impact: length of stay,
      transcription time, and laboratory use. We collected data on expenditures in
      these categories under the paper-based (pre-EMR) system, and then estimated
      reductions in each category based on findings from EMR systems in the USA and
      backed by ambulatory data from low-income settings. We compared these potential
      savings accrued over a period of 5 years with the costs of implementing the
      touchscreen point-of-care EMR system at that site. RESULTS: Estimated cost
      savings in length of stay, transcription time, and laboratory use totaled US$284
      395 annually. When compared with the costs of installing and sustaining the EMR
      system, there is a net financial gain by the third year of operation. Over 5
      years the estimated net benefit was US$613 681. DISCUSSION: Despite considering
      only three categories of savings, this analysis demonstrates the potential
      financial benefits of EMR systems in low-income settings. The results are robust
      to higher discount rates, and a net benefit is realized even under more
      conservative assumptions. CONCLUSIONS: This model demonstrates that financial
      benefits could be realized with an EMR system in a low-income setting. Further
      studies will examine these and other categories in greater detail, study the
      financial effects at different levels of organization, and benefit from post
      implementation data. This model will be further improved by substituting its
      assumptions for evidence as we conduct more detailed studies.

PMID- 23144337
TI  - Familial granulomatosis with polyangiitis: three cases of this rare disorder in
      one Indoasian family carrying an identical HLA DPB1 allele.
AB  - The aetiology of granulomatosis with polyangiitis (GPA) remains unclear. There is
      likely a complex interplay between environmental triggers and genetic
      predisposition. Early diagnosis and treatment improve outcome in this condition
      with an untreated reported mortality of 90%. There are a few cases of familial
      GPA in the literature, but we report here the interesting and rare scenario of
      three members of the same Indoasian family with GPA who share an identical human
      leucocyte antigen (HLA) haplotype. In particular, all three members of the family
      share the HLADPB1 allele *04 : 01. This is the first reported Indoasian family
      with GPA. The HLA antigens found on genotyping our family and, in particular,
      HLADPB1 has been linked with GPA in previous studies. Genome-wide association
      studies in Anti Neutrophil Cytoplasm Antibody (ANCA) associated vasculitis (AAV)
      are currently in progress and should improve understanding of the genetic aspects
      of this disease. There may be important implications for patients with GPA and
      for their relatives.

PMID- 23144336
TI  - Longitudinal analysis of pain in patients with metastatic prostate cancer using
      natural language processing of medical record text.
AB  - OBJECTIVES: To test the feasibility of using text mining to depict meaningfully
      the experience of pain in patients with metastatic prostate cancer, to identify
      novel pain phenotypes, and to propose methods for longitudinal visualization of
      pain status. MATERIALS AND METHODS: Text from 4409 clinical encounters for 33 men
      enrolled in a 15-year longitudinal clinical/molecular autopsy study of metastatic
      prostate cancer (Project to ELIminate lethal CANcer) was subjected to natural
      language processing (NLP) using Unified Medical Language System-based terms. A
      four-tiered pain scale was developed, and logistic regression analysis identified
      factors that correlated with experience of severe pain during each month.
      RESULTS: NLP identified 6387 pain and 13 827 drug mentions in the text. Graphical
      displays revealed the pain 'landscape' described in the textual records and
      confirmed dramatically increasing levels of pain in the last years of life in all
      but two patients, all of whom died from metastatic cancer. Severe pain was
      associated with receipt of opioids (OR=6.6, p<0.0001) and palliative radiation
      (OR=3.4, p=0.0002). Surprisingly, no severe or controlled pain was detected in
      two of 33 subjects' clinical records. Additionally, the NLP algorithm proved
      generalizable in an evaluation using a separate data source (889 Informatics for
      Integrating Biology and the Bedside (i2b2) discharge summaries). DISCUSSION:
      Patterns in the pain experience, undetectable without the use of NLP to mine the
      longitudinal clinical record, were consistent with clinical expectations,
      suggesting that meaningful NLP-based pain status monitoring is feasible. Findings
      in this initial cohort suggest that 'outlier' pain phenotypes useful for probing
      the molecular basis of cancer pain may exist. LIMITATIONS: The results are
      limited by a small cohort size and use of proprietary NLP software. CONCLUSIONS:
      We have established the feasibility of tracking longitudinal patterns of pain by
      text mining of free text clinical records. These methods may be useful for
      monitoring pain management and identifying novel cancer phenotypes.

PMID- 23144338
TI  - Bilateral paraganglioma.
AB  - A 41-year-old man presented with bilateral, painless, non-pulsatile left-sided
      neck swelling. This was noticed incidentally on a routine medical check-up. He
      had no significant medical history and did not take any regular medications.
      Urinary catecholamines and routine blood tests were all normal, and when he had
      been examined he was normotensive. The MRI scan revealed an enhancing lesion on
      the left side of the neck as seen in figure 1; it measured
      4&emsp14;cm*3&emsp14;cm and had a 'salt and pepper' appearance causing splaying
      of the internal and external carotid arteries at the level of the bulb. There was
      a similar enhancing lesion on the right side, measuring 2.6&emsp14;cm*2&emsp14;cm
      at the level of the carotid bifurcation and 5&emsp14;cm* 2.6&emsp14;cm at the
      jugular bulb, this is seen in figure 1. A diagnosis of bilateral paraganglioma
      was made.

PMID- 23144339
TI  - Mai infection simulating metastatic breast cancer.
AB  - We represent a case of an asymptomatic female who was found to have a mass in the
      right breast which confirmed an invasive ductal carcinoma by core biopsy. After
      3&emsp14;months of completion of chemo-radiotherapy, the patient remained totally
      asymptomatic. However, positron emission tomography scan showed four
      hypermetabolic lesions in the left lung thought to be consistent with metastatic
      disease. Standard uptake value ranged between 3.86 and 6; the results were
      consistent with metastatic breast cancer, so wedge resection was performed.
      Caseating granulomatous inflammation with necrosis was reported. Ultimately
      culture revealed Mycobacterium avium intracellulare infection. The lesions
      resolved completely after a course of antibiotics.

PMID- 23144340
TI  - Conservative treatment of a recto-urethral fistula due to salvage HIFU for local
      recurrence of prostate cancer, 5 years after radical prostatectomy and external
      beam radiotherapy.
AB  - Recto-urethral fistula is one of the most serious complications caused by high
      intensity-focused ultrasound used as salvage treatment for recurrence of prostate
      cancer after brachytherapy or external beam radiotherapy (EBRT). We report the
      case of a recto-urethral fistula in a 68-year-old patient, who previously had
      undergone radical prostatectomy and EBRT for prostate cancer (pT3 N0 Mx). The
      fistula was treated conservatively by an indwelling Foley catheter, without the
      creation of an intestinal diversion. The fistula was assessed initially by a
      retrograde and a CT scan of the pelvis with contrast medium and reassessed
      periodically by means of retrograde urethrograms. To date, 24 months after this
      episode, no evidence of recurrence of the fistula has been found.

PMID- 23144341
TI  - Diffuse epidermolytic palmoplantar keratoderma (Unna-Thost-).

PMID- 23144342
TI  - A 20-year-old female with Hirayama disease complicated with dysplasia of the
      cervical vertebrae and degeneration of intervertebral discs.
AB  - A 20-year-old female patient was presented with a 1-year history of progressive
      weakness of the left hand. Examination on admission showed atrophy of the muscles
      of the left forearm, cold paralysis and minipolymyoclonus. MR images of the
      cervical cord showed anterior transfer of the cervical cord on anterior flexion
      and cervical cord compression at the site of cervical kyphosis, confirming the
      diagnosis of Hirayama disease. Many features of the present case are unusual: the
      patient is a female (who are rarely afflicted by this disease), with cervical
      kyphosis and a history of exercise involving cervical vertebral loading,
      suggesting a potential involvement of the latter two factors in the disease
      onset. The findings suggest that cervical vertebral dysplasia and intervertebral
      disc degeneration may influence cervical kyphosis, and be involved in the onset
      of Hirayama disease.

PMID- 23144343
TI  - A rare CFTR intronic mutation related to a mild CF disease in a 12-year-old girl.
AB  - We report the case of a 12-year-old girl with an allergic bronchopulmonary
      aspergillosis (ABPA), intermediate sweat chloride tests and one cystic fibrosis
      (CF)-causing mutation, p.Phe508del. After extensive screening of the CF
      transmembrane regulator (CFTR) gene, she finally was found to carry a rare deep
      intronic mutation (c.872-1110_1113delGAAT), which confirmed the atypical mild CF
      disease. Although a classical steroid treatment did not allow the healing of the
      ABPA, an omalizumab therapy led to a long-term recovery. This case emphasises the
      need to search for rare CFTR gene mutations as far as possible when a CF disease
      is evocated. Moreover, it also highlights that although omalizumab is not yet
      recognised as a classical ABPA treatment in CF, it should be considered as an
      alternative therapy in steroid-resistant patients.

PMID- 23144344
TI  - Autologous adipose-tissue derived regenerative cells for the treatment of complex
      cryptoglandular fistula-in-ano: a report of three cases.
AB  - The treatment of complex fistulae-in-ano is challenging and often includes a
      number of operations due to high rates of recurrence. We report the successful
      treatment of three consecutive patients with long-standing cryptoglandular
      fistula-in-ano with a novel combination of mucosal advancement flap and adipose
      tissue derived regenerative cells (ADRCs) from the stromal vascular fraction
      (SVF) obtained from a simple lipoaspiration procedure, using Celution technology.
      There was no operative morbidity; one patient who had a colostomy for faecal
      diversion has since undergone restoration of bowel continuity. All thee fistulae
      remain healed at 2-3-year follow-up. Lipofilling of cryptoglandular fistulae-in
      ano with ADRC-enhanced lipofilling appears feasible and safe, and may add to the
      range of procedures that can be used to treat this difficult problem.

PMID- 23144345
TI  - Stroke and myocardial infarction: a terrible association.
AB  - In the USA coronary heart diseases and cerebral vascular accidents together are
      the major causes of death regardless of race or sex. More specifically, the acute
      myocardial infarction and the encephalic vascular accident, as final events of
      atherosclerosis, correspond to a large part of death cases. Such cases could be
      potentially prevented with a proper follow-up and the identification of the risk
      factors. We present a case of a 65-year-old black man, diabetic and hypertensive,
      with ischaemic stroke diagnosis that progressed to acute ST elevation myocardial
      infarction. Thrombolysis or platelets antiaggregation were not possible due to
      the fact that the patient was in the acute phase of his ischaemic stroke. This
      case shows the association of the two major causes of death in this country,
      stroke and myocardial infarction, and the challenge for their treatment.

PMID- 23144346
TI  - Multiple spontaneous enterocutaneous fistulae on back: a rare presentation of
      colonic malignancy.
AB  - We came across a case presenting with complaint of multiple fistulae present on
      back and lateral part of abdominal wall discharging faecal matter. Investigations
      revealed a fistulous tract arising from posterior wall of ascending colon. The
      patient did not respond to conservative management and therefore was subjected to
      exploratory laparotomy after thorough investigations. Peroperatively, an
      ileocaecal mass was found along with a fistulous tract which was arising from the
      posterior wall of ascending colon and communicating with the skin. A right
      haemicolectomy was performed followed by ileo-transverse anastomosis.
      Postoperative recovery was uneventful. The histopathology report came out to be
      adenocarcinoma of colon.

PMID- 23144347
TI  - Tension pneumothorax accompanied by type A aortic dissection.
AB  - A 51-year-old man was brought to the emergency room because of a sudden onset of
      severe dysponea. On presentation, his blood pressure was 94/55 mm Hg. Oxygen
      saturation was 86% while he was receiving 10 l/min oxygen through a non
      rebreather mask. On physical examination, no jugular venous distention was noted,
      but breath sounds over the left lung were diminished. A bedside chest radiograph
      showed left tension pneumothorax, for which urgent needle decompression followed
      by chest thoracostomy was performed. Ventricular tachycardia developed, but a
      biphasic shock at 120 J immediately restored normal sinus rhythm. His vital
      signs, however, did not improve. A CT scan of the chest showed type A aortic
      dissection with bullae in the upper lobe of the left lung. He had an emergency
      operation for distal aortic arch displacement and was discharged on the 37th day
      of hospitalisation.

PMID- 23144348
TI  - Intraventricular conduction defects.

PMID- 23144349
TI  - Interventional treatment for acute ischaemic stroke in an 86-year-old.
AB  - An 86-year-old lady presented to the accident and emergency department with a 90
      min history of receptive and expressive dysphasia. There were no motor symptoms
      or visual symptoms reported. A partial anterior circulation stroke was diagnosed.
      On examination, she had a National Institutes of Health Stroke Scale of 6. CT
      angiography showed an occlusive thrombus within the left internal carotid artery
      extending into the left M1 segment of the middle cerebral artery and the proximal
      A1 segment of the anterior cerebral artery. Intra-arterial thrombectomy was
      preformed. Full recovery was achieved.

PMID- 23144350
TI  - Efficacy and cost of micronutrient treatment of childhood psychosis.
AB  - Psychosis is difficult to treat effectively with conventional pharmaceuticals,
      many of which have adverse long-term health consequences. In contrast, there are
      promising reports from several research groups of micronutrient treatment
      (vitamins, minerals, amino acids and essential fatty acids) of mood, anxiety and
      psychosis symptoms using a complex formula that appears to be safe and tolerable.
      We review previous studies using this formula to treat mental symptoms, and
      present an 11-year-old boy with a 3-year history of mental illness whose parents
      chose to transition him from medication to micronutrients. Symptom severity was
      monitored in three clusters: anxiety, obsessive compulsive disorder and
      psychosis. Complete remission of psychosis occurred, and severity of anxiety and
      obsessional symptoms decreased significantly (p<0.001); the improvements are
      sustained at 4-year follow-up. A cost comparison revealed that micronutrient
      treatment was <1% of his inpatient mental healthcare. Additional research on
      broad-spectrum micronutrient treatment is warranted.

PMID- 23144352
TI  - Salmonellosis as a differential diagnosis.
AB  - With a low incidence of Salmonella infection, salmonellosis is an uncommon
      problem in Scotland. It occurs in both immune-compromised and immune-competent
      patients. We present two cases of salmonellosis in immune-competent patients who
      had had a history of gastroenteritis. Diagnosis was delayed in one patient;
      however, both patients received appropriate treatment and made good recovery
      following their respective illnesses. Apart from acting as a reminder to consider
      salmonellosis as a differential diagnosis when managing patients with infective
      process, the cases also highlight the importance of concise history taking, and
      the importance of cultures-and-sensitivities in managing infectious cases.

PMID- 23144351
TI  - Hypoglycaemia associated with co-trimoxazole use in a 56-year-old Caucasian woman
      with renal impairment.
AB  - Here we present a case of refractory hypoglycaemia associated with use of the
      antibiotic trimethoprim-sulfamethoxazole (TMP-SMX). This was used to treat
      Pneumocystis jirovecii pneumonia (PCP) infection. The patient had significant pre
      existing renal impairment with a kidney transplant in situ. Refractory
      hypoglycaemia occurred 5 days after starting the antibiotic and persisted for 36
      h after its cessation. SMX contains the same sulphanilamide structural group as
      the oral hypoglycaemic agents called sulphonureas. SMX could therefore act as an
      insulin secretagogue. The inappropriately raised insulin and c-peptide levels
      seen in our patient support this theory. The 5-day asymptomatic period would
      allow sufficient time for the drug to accumulate and the extended period seen
      after its cessation would be seen in a dose-dependent side effect. Following 3
      days of observation and continuous glycaemic support on the High Dependency Unit
      she was discharged back to the ward, with no further occurrence of hypoglycaemia.

PMID- 23144353
TI  - Neurocardiogenic syncope: a rare presentation of pharyngeal lymphoma.
AB  - Syncope is a common symptom of patients attending emergency departments, yet
      presents significant diagnostic and therapeutic challenges. We present a rare
      cause of recurrent vasovagal syncope with predominant cardioinhibitory response
      due to lymphoma surrounding and compressing the carotid artery treated
      successfully with radiotherapy.

PMID- 23144354
TI  - Dyspnoea-fasciculation syndrome: 'the clue is in the title'.

PMID- 23144355
TI  - Incidentally detected nasal foreign body on routine dental radiography.
AB  - A nasal foreign body was discovered on routine radiographic examination of a 7
      year-old girl following traumatic injury to permanent maxillary central incisors.
      The mother and the patient were unaware of the object's presence and the child
      had no nasal symptoms. The child was referred to an ear, nose and throat (ENT)
      surgeon to have the object assessed and removed. This was accomplished
      successfully without sequelae on an outpatient basis. This article highlights the
      role of a dentist in the proper detection and diagnosis, prompt referral for its
      management and reduction in complications related to foreign bodies.

PMID- 23144356
TI  - Vasculitis in a cocaine user.

PMID- 23144357
TI  - Non-contiguous spinal tuberculosis.

PMID- 23144358
TI  - Acute myocardial infarction in a young patient with hyperhomocysteinaemia.
AB  - Homocysteinuria is a rare inborn error of metabolism known to be associated with
      an increased risk of vascular events. A 36-year-old Caucasian man presented with
      a 2 day history of epigastric discomfort associated with nausea and sweating. He
      has a history of homocysteinuria and had been poorly compliant with treatment. An
      ECG showed ST-segment elevation and Q-waves in anterior leads. Blood tests showed
      markedly elevated high-sensitivity troponin and high homocysteine levels. He had
      a failed primary percutaneous coronary intervention due to extensive thrombus in
      the left anterior descending artery, which was aspirated and he received
      integrelin infusion for 48 h. Echocardiogram showed mild-to-moderate impairment
      of left ventricular function with apical akinesis extending to the mid-portion of
      anteroseptal walls consistent with anterior myocardial infarction. He was started
      on homocysteine-lowering treatment with betaine and folic acid. He is now on
      follow-up with clinical chemistry and cardiac rehabilitation.

PMID- 23144359
TI  - Sensitive and selective determination of diflunisal in human plasma by LC-MS.
AB  - A reliable and sensitive liquid chromatography-tandem mass spectrometry assay has
      been proposed for the selective determination of diflunisal in the presence of
      its glucuronide metabolites. The analyte and clofibric acid as internal standard
      (IS) are extracted from 50 uL of human plasma by solid-phase extraction.
      Chromatographic separation is conducted on a Prodigy ODS 3V column (150 * 4.6 mm,
      5 um) under isocratic conditions. The possible interference of acyl glucuronide
      and phenolic glucuronide, the two major inactive metabolites of diflunisal, is
      also checked in plasma samples. Detection of the analyte and IS is achieved by
      tandem mass spectrometry, operating in negative ionization and multiple reaction
      monitoring acquisition mode. The limits of detection and quantitation of the
      method are 0.10 and 1.00 ug/mL, respectively, with a linear dynamic range of 1.00
      160 ug/mL for diflunisal. The intra-batch and inter-batch precision (percent
      coefficient of variation) is <=4.2% and the mean recovery is >92% for diflunisal
      across quality control levels. The method is successfully applied to a
      bioequivalence study of a 500 mg diflunisal tablet formulation in 30 healthy
      Indian male subjects under fasting conditions. The reproducibility in the
      measurement of study data is demonstrated by the reanalysis of 120 incurred
      samples. 

PMID- 23144360
TI  - Phylogeny of palaeotropic Derris-like taxa (Fabaceae) based on chloroplast and
      nuclear DNA sequences shows reorganization of (infra)generic classifications is
      needed.
AB  - PREMISE OF THE STUDY: Palaeotropic Derris-like taxa (family Fabaceae, tribe
      Millettieae) comprise 6-9 genera. They are well known as important sources of
      rotenone toxin, which are used as organic insecticide and fish poison. However,
      their phylogenetic relationships and classification are still problematic due to
      insufficient sampling and high morphological variability. METHODS: Fifty species
      of palaeotropic Derris-like taxa were sampled, which is more than in former
      studies. Three chloroplast genes (trnK-matK, trnL-F IGS, and psbA-trnH IGS) and
      nuclear ribosomal ITS /5.8S were analyzed using parsimony and Bayesian methods.
      KEY RESULTS: Parsimony and Bayesian analyses of individual and combined markers
      show more or less similar tree topologies (only varying in terminal branches).
      The old-world monophyletic genera Aganope, Brachypterum, and Leptoderris are
      distinct from Derris s.s., and their generic status is here confirmed. Aganope
      may be classified into two or three subgeneric taxa. Paraderris has to be
      included in Derris s.s. to form a monophyletic group. The genera Philenoptera,
      Deguelia, and Lonchocarpus are monophyletic and distinct from each other and
      clearly separate from Derris s.s. Morphologically highly similar species of
      Derris s.s. are shown to be unrelated. Our study shows that previous infrageneric
      classifications of Derris are incorrect. Paraderris elliptica may contain several
      cryptic lineages that need further investigation. CONCLUSIONS: The concept of the
      genus Derris s.s. should be reorganized with a new generic circumscription by
      including Paraderris but excluding Brachypterum. Synapomorphic morphological
      features will be examined in future studies, and the status of the newly defined
      Derris and its closely related taxa will be formalized.

PMID- 23144361
TI  - Evaluation of genome-wide association study-identified type 2 diabetes loci in
      African Americans.
AB  - Type 2 diabetes (T2D) is up to twice as prevalent among African Americans as
      Caucasians. Recent genome-wide association studies (GWAS) have identified
      multiple common genetic risk variants for T2D; however, none of these studies
      were conducted exclusively among subjects of African ancestry. Investigating
      these known loci in other populations would be an expedient way to evaluate the
      generalizability of the current findings. The authors evaluated 29 known T2D loci
      in a large southeastern US cohort study including 4,288 African Americans (1,554
      cases and 2,734 controls) enrolled during 2002-2009. Seven of the 29 single
      nucleotide polymorphisms (SNPs) examined were found to be associated with T2D
      risk at P <= 0.05, including rs6769511 (IGF2BP2), 2 SNPs in the WFS1 gene
      (rs4689388 and rs1801214), rs7903146 (TCF7L2), and 3 SNPs in the KCNQ1 gene
      (rs231362, rs2237892, and rs2237897). Notably, the association for rs7903146
      reached the GWAS significance level (P = 3.6 * 10(-8)), with an odds ratio per T
      allele of 1.32 (95% confidence interval: 1.20, 1.46). Regional analyses using
      GWAS data from Vanderbilt University's BioVU DNA biobank showed significant
      associations (P < 0.05) with 9 loci, though no association was observed for the
      index SNPs reported in European- or Asian-ancestry populations. These results
      extend some of the recent GWAS findings to African Americans and may guide future
      efforts to identify causal variants for T2D.

PMID- 23144362
TI  - Comparisons of the strength of associations with future type 2 diabetes risk
      among anthropometric obesity indicators, including waist-to-height ratio: a meta
      analysis.
AB  - The aim of this meta-analysis was to compare the association of waist-to-height
      ratio (WHtR) with risk of incident diabetes with the associations of 3 other
      conventional obesity indicators (body mass index (BMI), waist circumference (WC),
      and waist-to-hip ratio (WHR)) with risk of incident diabetes. Literature searches
      in MEDLINE (January 1950 to April 27, 2011) and EMBASE (January 1974 to April 27,
      2011) were conducted for prospective studies that made it possible to estimate
      the relative risk of diabetes per 1-standard deviation increase in WHtR, in
      addition to the RR of BMI, WC, or WHR. Strength of the estimated pooled relative
      risk for a 1-standard deviation increase of each indicator (expressed as
      RR(WHtR), RR(BMI), RR(WC), and RR(WHR)) was compared with a bivariate random
      effects model. Pooled relative risks of the 15 eligible studies with 6,472
      diabetes cases were 1.62 (95% CI: 1.48, 1.78) for RR(WHtR), 1.55 (95% CI: 1.43,
      1.69) for RR(BMI), 1.63 (95% CI: 1.49, 1.79) for RR(WC), and 1.52 (95% CI: 1.40,
      1.66) for RR(WHR). WHtR had an association stronger than that of BMI (P<0.001) or
      WHR (P<0.001). The present meta-analysis showed that WHtR has a modestly but
      statistically greater importance than BMI and WHR in prediction of diabetes.
      Nevertheless, measuring height in addition to WC appeared to have no additional
      benefit.

PMID- 23144363
TI  - Invited commentary: job strain and health behaviors--developing a bigger picture.
AB  - Investigation of the association between job stressors and health behaviors has a
      long history that has been marked by mixed findings. Fransson et al. (Am J
      Epidemiol. 2012;176(12):1078-1089) find robust prospective and cross-sectional
      associations between job strain and leisure-time physical inactivity in combined
      data from 14 cohort studies. Further research to better understand the observed
      heterogeneity in the contributing cohorts and other studies will be crucial for
      application to intervention design and tailoring. The population health
      significance of these findings requires consideration of other job strain-health
      behavior (particularly the parallel analyses conducted for body mass index and
      smoking in the same data set) and job strain-health outcome associations, as well
      as these same associations for other job stressors. Job strain can be seen as a
      "fundamental cause" of work-related disease, in that intervention to reduce
      exposure to job strain could have beneficial impacts on many outcomes, making a
      compelling case for intervention. The significantly strengthened evidence linking
      job stressors to health behaviors provided by Fransson et al. may help to further
      direct workplace health promotion research, policy, and practice towards an
      approach that better integrates intervention on working conditions and health
      behaviors. The benefits to population health could be substantial.

PMID- 23144365
TI  - Need for more individual-level meta-analyses in social epidemiology: example of
      job strain and coronary heart disease.
AB  - In genetics, major progress was made after pooling of data sets to mega-studies
      became the norm in the field. In the present commentary, the authors ask whether
      such an approach would also be worthy of broader application in the field of
      social epidemiology. Research on job strain and coronary heart disease provides
      an illustrative example. Over 3 decades, debate has continued as to the relative
      importance of high psychological demands versus low control-that is, whether one
      component of job strain is more toxic than the other-and differences by age and
      sex. Recently, these controversies were largely resolved in an individual
      participant meta-analysis of 200,000 participants from 13 cohorts: The
      combination of both high demands and low control was a greater risk factor than
      either of the components alone, there were no differences in the associations of
      job strain with CHD between men and women, between the young and old, or at
      different levels of socioeconomic position, and the impact was more modest when
      unpublished data were included but was still robust to all adjustments. The fact
      that longstanding debates in the job strain literature were resolved by applying
      an individual-participant data meta-analysis approach suggests that lessons
      learned in genetics might also apply to social epidemiology.

PMID- 23144364
TI  - Job strain as a risk factor for leisure-time physical inactivity: an individual
      participant meta-analysis of up to 170,000 men and women: the IPD-Work
      Consortium.
AB  - Unfavorable work characteristics, such as low job control and too high or too low
      job demands, have been suggested to increase the likelihood of physical
      inactivity during leisure time, but this has not been verified in large-scale
      studies. The authors combined individual-level data from 14 European cohort
      studies (baseline years from 1985-1988 to 2006-2008) to examine the association
      between unfavorable work characteristics and leisure-time physical inactivity in
      a total of 170,162 employees (50% women; mean age, 43.5 years). Of these
      employees, 56,735 were reexamined after 2-9 years. In cross-sectional analyses,
      the odds for physical inactivity were 26% higher (odds ratio = 1.26, 95%
      confidence interval: 1.15, 1.38) for employees with high-strain jobs (low
      control/high demands) and 21% higher (odds ratio = 1.21, 95% confidence interval:
      1.11, 1.31) for those with passive jobs (low control/low demands) compared with
      employees in low-strain jobs (high control/low demands). In prospective analyses
      restricted to physically active participants, the odds of becoming physically
      inactive during follow-up were 21% and 20% higher for those with high-strain
      (odds ratio = 1.21, 95% confidence interval: 1.11, 1.32) and passive (odds ratio
      = 1.20, 95% confidence interval: 1.11, 1.30) jobs at baseline. These data suggest
      that unfavorable work characteristics may have a spillover effect on leisure-time
      physical activity.

PMID- 23144366
TI  - Clinically relevant injury patterns after an anterior cruciate ligament injury
      provide insight into injury mechanisms.
AB  - BACKGROUND: The functional disability and high costs of treating anterior
      cruciate ligament (ACL) injuries have generated a great deal of interest in
      understanding the mechanism of noncontact ACL injuries. Secondary bone bruises
      have been reported in over 80% of partial and complete ACL ruptures. PURPOSE: The
      objectives of this study were (1) to quantify ACL strain under a range of
      physiologically relevant loading conditions and (2) to evaluate soft tissue and
      bony injury patterns associated with applied loading conditions thought to be
      responsible for many noncontact ACL injuries. STUDY DESIGN: Controlled laboratory
      study. METHODS: Seventeen cadaveric legs (age, 45 +/- 7 years; 9 female and 8
      male) were tested utilizing a custom-designed drop stand to simulate landing.
      Specimens were randomly assigned between 2 loading groups that evaluated ACL
      strain under either knee abduction or internal tibial rotation moments. In each
      group, combinations of anterior tibial shear force, and knee abduction and
      internal tibial rotation moments under axial impact loading were applied
      sequentially until failure. Specimens were tested at 25 degrees  of flexion under
      simulated 1200-N quadriceps and 800-N hamstring loads. A differential variable
      reluctance transducer was used to calculate ACL strain across the anteromedial
      bundle. A general linear model was used to compare peak ACL strain at failure.
      Correlations between simulated knee injury patterns and loading conditions were
      evaluated by the chi2 test for independence. RESULTS: Anterior cruciate ligament
      failure was generated in 15 of 17 specimens (88%). A clinically relevant
      distribution of failure patterns was observed including medial collateral
      ligament tears and damage to the menisci, cartilage, and subchondral bone. Only
      abduction significantly contributed to calculated peak ACL strain at failure (P =
      .002). While ACL disruption patterns were independent of the loading mechanism,
      tibial plateau injury patterns (locations) were significantly (P = .002)
      dependent on the applied loading conditions. Damage to the articular cartilage
      along with depression of the midlateral tibial plateau was primarily associated
      with knee abduction moments, while cartilage damage with depression of the
      posterolateral tibial plateau was primarily associated with internal tibial
      rotation moments. CONCLUSION: The current findings demonstrate the relationship
      between the location of the tibial plateau injury and ACL injury mechanisms. The
      resultant injury locations were similar to the clinically observed bone bruises
      across the tibial plateau during a noncontact ACL injury. These findings indicate
      that abduction combined with other modes of loading (multiplanar loading) may act
      to produce ACL injuries. CLINICAL RELEVANCE: A better understanding of ACL injury
      mechanisms and associated risk factors may improve current preventive, surgical,
      and rehabilitation strategies and limit the risk of ACL and secondary injuries,
      which may in turn minimize the future development of posttraumatic osteoarthritis
      of the knee.

PMID- 23144367
TI  - Anatomic femoral tunnels in posterior cruciate ligament reconstruction: inside
      out versus outside-in drilling.
AB  - BACKGROUND: During posterior cruciate ligament (PCL) reconstruction, the
      placement and orientation of the femoral tunnel is critical to postoperative PCL
      function. PURPOSE: To compare the ability of outside-in (OI) versus inside-out
      (IO) femoral tunnel drilling in placing the femoral tunnel aperture within the
      anatomic femoral footprint of the PCL, and to evaluate the orientation of the
      tunnels within the medial femoral condyle. STUDY DESIGN: Controlled laboratory
      study. METHODS: Ten matched pairs of cadaver knees were randomized such that
      within each pair, 1 knee underwent arthroscopic OI drilling and the other
      underwent IO drilling. All knees underwent computed tomography (CT) both pre- and
      postoperatively with a technique optimized for ligament evaluation (80 keV with
      maximum mAs). Commercially available third-party software was used to fuse the
      pre- and postoperative CT scans, allowing comparison of the PCL footprint to the
      drilled tunnel. The percentage of tunnel aperture contained within the native
      footprint, as well as the distance from the center of the tunnel aperture to the
      center of the footprint, were measured. In addition, the orientation of the
      tunnels in the coronal and axial planes was evaluated. RESULTS: The OI technique
      placed 70.4% +/- 23.7% of the tunnel within the native femoral footprint compared
      with 79.8% +/- 16.7% for the IO technique (P = .32). The OI technique placed the
      center of the femoral tunnel 4.9 +/- 2.2 mm from the center of the native
      footprint compared to 5.3 +/- 2.0 mm for the IO technique (P = .65). The femoral
      tunnel angle in the coronal plane was 21.0 degrees  +/- 9.9 degrees  for the OI
      technique and 37.0 degrees  +/- 10.3 degrees  for the IO technique (P = .002).
      The tunnel angle in the axial plane was 27.3 degrees  +/- 4.8 degrees  for the OI
      technique and 39.1 degrees  +/- 11.5 degrees  for the IO technique (P = .01).
      CONCLUSION: This study demonstrates no difference in the ability of the OI and IO
      techniques to place the femoral tunnel within the PCL femoral footprint during
      PCL reconstruction. With the technique parameters used in this study, the IO
      technique created femoral tunnels with a more vertical and anterior orientation
      than the OI technique. CLINICAL RELEVANCE: Either technique can be used to place
      the femoral tunnel within the anatomic footprint. Consideration should be given
      to tunnel orientation following each technique, and what effect it has on graft
      bending angles, as these characteristics may affect graft strain and, ultimately,
      graft failure. In this regard, the IO technique likely produces gentler graft
      bending angles.

PMID- 23144368
TI  - Sensitivity and specificity of the online version of ImPACT in high school and
      collegiate athletes.
AB  - BACKGROUND: The utility of postconcussion neurocognitive testing versus symptom
      data has been debated. The sensitivity of the desktop version of the Immediate
      Post-concussion assessment and cognitive testing (ImPACT) tool has been
      documented, but psychometric properties of the recently released online version
      of ImPACT have yet to be fully established. PURPOSE: To document the sensitivity
      of the online ImPACT version in samples of (1) symptomatic concussed (high school
      and collegiate) athletes, and (2) asymptomatic concussed (high school and
      collegiate) athletes suspected of hiding their concussions. STUDY DESIGN: Cohort
      study; level of evidence, 3. METHODS: A total of 81 athletes observed to sustain
      a concussion by a certified athletic trainer or team physician, a finding that
      was confirmed with reported postconcussion symptoms, completed the ImPACT test
      within 3 days of injury. Data were compared with an independent sample of 81
      athletes who completed preseason baseline cognitive assessments using ImPACT and
      who were matched (with concussed athletes) on the basis of sex, age, sport,
      concussion history, and absence of attention deficit hyperactivity disorder and
      learning disability. An independent group of 37 athletes who were also observed
      to sustain a concussion completed ImPACT within 3 days of injury. These athletes
      reported no postconcussion symptoms but were noted for suspected invalid response
      patterns on ImPACT (impulse control index >30 and verbal memory index <69%). The
      subscale data from the assessments (excluding those contributing to the
      aforementioned indices) were compared with a matched sample of 37 athletes who
      completed preseason baseline cognitive assessments in ImPACT (using the same
      criteria described above). RESULTS: Data from the ImPACT online version yielded
      91.4% sensitivity and 69.1% specificity. For asymptomatic athletes suspected of
      hiding their concussion, data from ImPACT yielded 94.6% sensitivity and 97.3%
      specificity. CONCLUSION: The online version of the ImPACT tool is a valid measure
      of neurocognitive performance at the acute stages of concussion, with high levels
      of sensitivity and specificity, even when athletes appear to be denying
      postconcussion symptoms.

PMID- 23144369
TI  - Radiographic landmarks for tunnel positioning in posterior cruciate ligament
      reconstructions.
AB  - BACKGROUND: Consistent radiographic guidelines for tunnel placement in single- or
      double-bundle posterior cruciate ligament (PCL) reconstructions are not well
      defined. Quantitative guidelines reporting the location of the individual PCL
      bundle attachments would aid in intraoperative tunnel placement and postoperative
      assessment of a PCL reconstruction. HYPOTHESIS: Consistent and reproducible
      measurements in relation to radiographic landmarks for the entire PCL and its
      individual bundle attachments are achievable. STUDY DESIGN: Controlled laboratory
      study. METHODS: The femoral and tibial PCL bundle attachment centers of 20
      nonpaired fresh-frozen cadaveric knees were labeled using radio-opaque spheres
      and the attachment areas were labeled using barium sulfate. Anteroposterior (AP)
      and lateral radiographs of the femur and tibia were obtained, and measurements of
      the distances between the PCL bundle centers and landmarks were acquired.
      RESULTS: On the AP femur view, the anterolateral bundle (ALB) and posteromedial
      bundle (PMB) centers were 34.1 +/- 3.0 mm and 29.2 +/- 3.0 mm lateral to the most
      medial border of the medial femoral condyle, respectively. The lateral femur
      images revealed that the ALB center was 17.4 +/- 1.7 mm and the PMB center was
      23.9 +/- 2.7 mm posteroproximal to a line perpendicular to the Blumensaat line
      that intersected the anterior margin of the medial femoral condyle cortex.
      Anteroposterior tibia images revealed that the ALB and PMB centers were located
      0.2 +/- 2.1 mm proximal and 4.9 +/- 2.9 mm distal to the proximal joint line,
      respectively. The PCL attachment center was 1.6 +/- 2.5 mm distal to the proximal
      joint line. On the lateral tibia view, the ALB center was 8.4 +/- 1.8 mm, the PCL
      attachment center was 5.5 +/- 1.7 mm, and the PMB center was 2.5 +/- 1.5 mm
      superior to the champagne glass drop-off of the posterior tibia. CONCLUSION:
      Radiographic measurements from several clinically relevant views of the femur and
      tibia were reproducible with regard to the anatomic locations of the ALB and PMB
      centers. The measurements from the lateral femur and tibia views provided the
      most clinically pertinent radiographic measurements intraoperatively. CLINICAL
      RELEVANCE: This study established a set of clinically relevant radiographic
      guidelines for anatomic reconstruction of the PCL. The parameters set forth in
      this study can be used in both the intraoperative and postoperative settings for
      both single- and double-bundle PCL reconstructions.

PMID- 23144370
TI  - The effect of initial graft tension after anterior cruciate ligament
      reconstruction: a randomized clinical trial with 36-month follow-up.
AB  - BACKGROUND: The initial graft tension applied at the time of anterior cruciate
      ligament (ACL) reconstruction alters joint contact and may influence cartilage
      health. The objective was to compare outcomes between 2 commonly used "laxity
      based" initial graft tension protocols. HYPOTHESES: (1) The high-tension group
      would have less knee laxity, improved clinical and patient-oriented outcomes, and
      less cartilage damage than would the low-tension group after 36 months of
      healing. (2) The outcomes of the high-tension group would be equivalent to those
      of a matched control group. STUDY DESIGN: Randomized controlled trial; Level of
      evidence, 1. METHODS: Ninety patients with isolated unilateral ACL injuries were
      randomized to undergo ACL reconstruction using 1 of 2 initial graft tension
      protocols: (1) autografts tensioned to restore normal anterior-posterior (AP)
      laxity at the time of surgery (ie, low tension; n = 46) and (2) autografts
      tensioned to overconstrain AP laxity by 2 mm (ie, high tension; n = 44). Sixty
      matched healthy patients formed the control group. Outcomes were assessed
      preoperatively, intraoperatively, and at 6, 12, and 36 months after surgery.
      RESULTS: No significant differences were found between the 2 initial graft
      tension protocols for any of the outcome measures at 36 months. However, there
      were differences when comparing the 2 treatment groups to the control group. On
      average, AP laxity was 2 mm greater in the ACL-reconstructed groups than in the
      control group (P < .007). International Knee Documentation Committee (IKDC) knee
      evaluation scores, peak isokinetic knee extension torques, and 4 of 5 Knee
      Osteoarthritis Outcome Scores (KOOS) were significantly worse than the control
      group (P < .001, P < .027, and P < .05, respectively). Short Form-36 Health
      Survey (SF-36) scores and reinjury rates were similar between groups at 36
      months. Although there were significant changes in radiography and magnetic
      resonance imaging present in the ACL-reconstructed knees of both treatment
      groups, the magnitude was relatively small and likely clinically insignificant at
      36 months. CONCLUSION: Both laxity-based initial graft tension protocols produced
      similar outcomes without fully restoring joint function or patient-oriented
      outcomes (KOOS) when compared with the control group. There was minimal evidence
      of cartilage damage 36 months after surgery.

PMID- 23144371
TI  - First genome sequence of a Burkholderia pseudomallei Isolate in China, strain
      BPC006, obtained from a melioidosis patient in Hainan.
AB  - Melioidosis, caused by Burkholderia pseudomallei, is considered to be endemic to
      Northern Australia and Southeast Asia, with high mortality and relapse rates,
      regardless of powerful antibiotic therapy. Here we report the first genome
      sequence of Burkholderia pseudomallei strain BPC006, obtained from a melioidosis
      patient in Hainan, China. The genome sizes of the 2 chromosomes were determined
      to be 4,001,777 bp and 3,153,284 bp.

PMID- 23144372
TI  - Draft genome sequence of Actinobacillus pleuropneumoniae serotype 7 strain S-8.
AB  - The Gram-negative bacterium Actinobacillus pleuropneumoniae is the etiological
      agent of porcine pleuropneumonia, a respiratory disease that leads to severe
      economic losses in the swine industry. For years, scientists working with it have
      lacked a reliable genome sequence for comparison with other Actinobacillus
      species. Here, we report the draft genome sequence of A. pleuropneumoniae
      serotype 7 (strain S-8), isolated from swine lung in China in 1992.

PMID- 23144373
TI  - Genome sequence of Halorubrum sp. strain T3, an extremely halophilic archaeon
      harboring a virus-like element.
AB  - Halorubrum sp. strain T3, harboring a virus-like element, was isolated from a
      sample collected from a solar saltern in Yunnan, China. Several strains of
      Halorubrum pleomorphic viruses were reported in this genus recently; however, the
      virus-host interaction in haloarchaea remains unclear. To explore this issue,
      here we present the genome sequence of Halorubrum sp. strain T3 (3,168,011 bp,
      68.48% G+C content).

PMID- 23144374
TI  - Draft genome sequence of Pantoea sp. strain A4, a Rafflesia-associated bacterium
      that produces N-acylhomoserine lactones as quorum-sensing molecules.
AB  - Pantoea sp. strain A4 is a Gram-negative bacterium isolated from the Rafflesia
      flower. We present here, for the first time, the genome sequence of Rafflesia
      associated Pantoea sp. strain A4, which exhibited quorum-sensing activity.

PMID- 23144375
TI  - Insights from the genome sequence of quorum-quenching Staphylococcus sp. strain
      AL1, isolated from traditional Chinese soy sauce brine fermentation.
AB  - We report the draft genome sequence of Staphylococcus sp. strain AL1, which
      degrades quorum-sensing molecules (namely, N-acyl homoserine lactones). To the
      best of our knowledge, this is the first documentation that reports the whole
      genome sequence and quorum-quenching activity of Staphylococcus sp. strain AL1.

PMID- 23144376
TI  - Draft genome sequences of Actinomyces timonensis strain 7400942T and its
      prophage.
AB  - A draft genome sequence of Actinomyces timonensis, an anaerobic bacterium
      isolated from a human clinical osteoarticular sample, is described here. CRISPR
      associated proteins, insertion sequence, and toxin-antitoxin loci were found on
      the genome. A new virus or provirus, AT-1, was characterized.

PMID- 23144377
TI  - Genome sequence of Staphylococcus arlettae strain CVD059, isolated from the blood
      of a cardiovascular disease patient.
AB  - We have isolated a Staphylococcus arlettae strain, strain CVD059, from the blood
      of a rheumatic mitral stenosis patient. Here, we report the genome sequence and
      potential virulence factors of this clinical isolate. The draft genome of S.
      arlettae CVD059 is 2,565,675 bp long with a G+C content of 33.5%.

PMID- 23144378
TI  - Draft genome sequence for Pseudomonas aeruginosa strain PAO579, a mucoid
      derivative of PAO381.
AB  - Pseudomonas aeruginosa is an opportunistic pathogen that establishes a chronic
      lung infection in individuals afflicted with cystic fibrosis. Here, we announce
      the draft genome of P. aeruginosa strain PAO579, an alginate-overproducing
      derivative of strain PAO381.

PMID- 23144379
TI  - Draft genome sequence of the cyanide-utilizing bacterium Pseudomonas fluorescens
      strain NCIMB 11764.
AB  - We report here the 6.97-Mb draft genome sequence of Pseudomonas fluorescens
      strain NCIMB 11764, which is capable of growth on cyanide as the sole nitrogen
      source. The draft genome sequence allowed the discovery of several genes
      implicated in enzymatic cyanide turnover and provided additional information
      contributing to a better understanding of this organism's unique cyanotrophic
      ability. This is the first sequenced genome of a cyanide-assimilating bacterium.

PMID- 23144380
TI  - Genome sequence of the Corynebacterium pseudotuberculosis Cp316 strain, isolated
      from the abscess of a Californian horse.
AB  - The bacterium Corynebacterium pseudotuberculosis is of major veterinary
      importance because it affects livestock, particularly sheep, goats, and horses,
      in several countries, including Australia, Brazil, the United States, and Canada,
      resulting in significant economic losses. In the present study, we describe the
      complete genome of the Corynebacterium pseudotuberculosis Cp316 strain, biovar
      equi, isolated from the abscess of a North American horse.

PMID- 23144381
TI  - Draft genome sequence of marine-derived Streptomyces sp. strain AA0539, isolated
      from the Yellow Sea, China.
AB  - Here, we report the draft genome sequence of Streptomyces sp. strain AA0539,
      isolated from marine sediment of the Yellow Sea, China. Its small genome (~5.8
      Mb) contains large, unique genes and gene clusters for diverse secondary
      metabolites, suggesting great potential as a source for the discovery of novel
      natural products.

PMID- 23144382
TI  - Draft genome sequence of Bacillus isronensis strain B3W22, isolated from the
      upper atmosphere.
AB  - We report the 4.0-Mb genome sequence of Bacillus isronensis strain B3W22 isolated
      from air collected at an altitude ranging from 27 to 30 km above the city of
      Hyderabad, in India. This genome sequence will contribute to the objective of
      determining the microbial diversity of the upper atmosphere.

PMID- 23144383
TI  - Draft genome sequence of the methane-oxidizing bacterium Methylococcus capsulatus
      (Texas).
AB  - Methanotrophic bacteria perform major roles in global carbon cycles via their
      unique enzymatic activities that enable the oxidation of one-carbon compounds,
      most notably methane. Here we describe the annotated draft genome sequence of the
      aerobic methanotroph Methylococcus capsulatus (Texas), a type strain originally
      isolated from sewer sludge.

PMID- 23144384
TI  - whole-genome sequence of livestock-associated st398 methicillin-resistant
      staphylococcus aureus Isolated from Humans in Canada.
AB  - Despite reports of high colonization rates of ST398 livestock-associated
      methicillin-resistant Staphylococcus aureus (LA-MRSA) among pigs and pig farmers,
      the incidence of LA-MRSA infection in the general population in Canada appears to
      be rare in comparison to that in some European countries. In this study, the
      complete genome sequence of a Canadian representative LA-MRSA isolate (08BA02176)
      from a human postoperative surgical site infection was acquired and compared to
      the sequenced genome of an LA-MRSA isolate (S0385) from Europe to identify
      genetic traits that may explain differences in the success of these particular
      strains in some locales.

PMID- 23144386
TI  - Draft genome sequence of Cecembia lonarensis strain LW9T, isolated from Lonar
      Lake, a haloalkaline lake in India.
AB  - The draft genome sequence (4.84 Mb) of Cecembia lonarensis strain LW9(T),
      isolated from a water sample (4.5-m depth) from Lonar Lake, a meteorite-created
      haloalkaline lake in India, is reported. The enzymes produced by these
      microorganisms need to be stable under alkaline conditions prevailing in its
      habitat. Such enzymes would be of immense importance for enzymatic processes
      operating at high pH.

PMID- 23144385
TI  - Genome sequence of Janibacter hoylei MTCC8307, isolated from the stratospheric
      air.
AB  - Janibacter hoylei MTCC8307 was isolated from stratospheric air at an altitude of
      41.4 km over Hyderabad, India. Here, we present the draft genome of Janibacter
      hoylei MTCC8307, which contains 3,139,099 bp with a G+C content of 72.8 mol%,
      2,972 protein-coding genes, and 57 structural RNAs.

PMID- 23144387
TI  - Draft genome sequence of strain P7-3-5, a new Flavobacteriaceae bacterium
      isolated from intertidal sand.
AB  - The Flavobacteriaceae bacterium strain P7-3-5 was isolated from intertidal sand
      of the Yellow Sea, China. Analysis of the 16S rRNA gene sequences showed that
      strain P7-3-5 formed a distinct phylogenetic lineage within the family
      Flavobacteriaceae. The genome of strain P7-3-5 was sequenced to facilitate the
      physiological, ecological, and evolutionary studies of the bacteria within the
      family Flavobacteriaceae.

PMID- 23144388
TI  - Genome sequence of the aerobic bacterium Bacillus sp. strain FJAT-13831.
AB  - Bacillus sp. strain FJAT-13831 was isolated from the no. 1 pit soil of Emperor
      Qin's Terracotta Warriors in Xi'an City, People's Republic of China. The isolate
      showed a close relationship to the Bacillus cereus group. The draft genome
      sequence of Bacillus sp. FJAT-13831 was 4,425,198 bp in size and consisted of
      5,567 genes (protein-coding sequences [CDS]) with an average length of 782 bp and
      a G+C value of 36.36%.

PMID- 23144389
TI  - Draft genome sequence of Brevibacillus brevis strain X23, a biocontrol agent
      against bacterial wilt.
AB  - Brevibacillus brevis X23 is an appropriate biocontrol agent against bacterial
      wilt caused by Ralstonia solanacearum. We report herein the draft genome sequence
      (6,566,879 bp) and a circular plasmid (6,600 bp) of B. brevis X23, data which may
      be helpful for mining the antagonistic activity against R. solanacearum.

PMID- 23144390
TI  - Draft genome sequence of Paenisporosarcina sp. strain TG-20, a psychrophilic
      bacterium isolated from the basal ice of Taylor Glacier.
AB  - We report the draft genome sequence of Paenisporosarcina sp. strain TG-20, which
      is 4.12 Mb in size and consists of 4,071 protein-coding genes and 76 RNA genes.
      The genome sequence of Paenisporosarcina sp. TG-20 may provide useful information
      about molecular adaptations that enhance survival in icy subsurface environments.

PMID- 23144391
TI  - Genome sequence of Leuconostoc pseudomesenteroides strain 4882, isolated from a
      dairy starter culture.
AB  - The nonstarter lactic acid bacterium Leuconostoc pseudomesenteroides is a species
      widely found in the dairy industry and plays a key role in the formation of
      aromatic compounds. Here, we report the first genome sequence of a dairy strain
      of Leuconostoc pseudomesenteroides, which is 2 Mb.

PMID- 23144392
TI  - Draft genome sequence of Lactobacillus casei W56.
AB  - We announce the draft genome sequence of Lactobacillus casei W56 in one contig.
      This strain shows immunomodulatory and probiotic properties. The strain is also
      an ingredient of commercially available probiotic products.

PMID- 23144393
TI  - Genome sequence of Staphylococcus epidermidis strain AU12-03, isolated from an
      intravascular catheter.
AB  - In recent years, Staphylococcus epidermidis has become a major nosocomial
      pathogen and the most common cause of intravascular catheter-related bacteremia,
      which can increase morbidity and mortality and significantly affect patient
      recovery. We report a draft genome sequence of Staphylococcus epidermidis AU12
      03, isolated from an intravascular catheter tip.

PMID- 23144394
TI  - Draft Genome sequence of Escherichia coli AI27, a porcine isolate belonging to
      phylogenetic group B1.
AB  - Escherichia coli AI27 is a putatively commensal strain isolated from feces of a
      pig. Here we report the draft genome sequence of E. coli AI27. This is the first
      porcine strain in the phylogenetic group B1 whose genome sequence has been
      determined.

PMID- 23144395
TI  - Complete genome sequence of the naphthalene-degrading bacterium Pseudomonas
      stutzeri AN10 (CCUG 29243).
AB  - Pseudomonas stutzeri AN10 (CCUG 29243) can be considered a model strain for
      aerobic naphthalene degradation. We report the complete genome sequence of this
      bacterium. Its 4.71-Mb chromosome provides insights into other biodegradative
      capabilities of strain AN10 (i.e., benzoate catabolism) and suggests a high
      number of horizontal gene transfer events.

PMID- 23144396
TI  - Draft genome sequence of the fish pathogen Vibrio harveyi strain ZJ0603.
AB  - Vibrio harveyi is an important pathogen that causes vibriosis in various aquatic
      organisms. Here, we announce the draft genome sequence of V. harveyi strain
      ZJ0603, which was isolated from diseased Orange-spotted grouper (Epinephelus
      coioides) in Guangdong, China.

PMID- 23144397
TI  - Draft genome sequence of Rahnella aquatilis strain HX2, a plant growth-promoting
      rhizobacterium isolated from vineyard soil in Beijing, China.
AB  - Rahnella aquatilis strain HX2 is a plant growth-promoting, disease-suppressive
      rhizobacterium that was isolated from a vineyard soil in Beijing, China. Here, we
      report the genome sequence of this strain, which provides a valuable resource for
      future research examining the mechanisms of traits associated with plant growth
      promotion and biocontrol.

PMID- 23144398
TI  - Draft genome sequence of the novel enteric bacterium Galloisinimonas intestini
      B14T KCTC 32180, isolated from the gut of a Galloisiana species (Notoptera:
      Grylloblattidae) fossil insect.
AB  - We report the 3.74-Mb genome sequence of Galloisinimonas intestini B14(T),
      isolated from the gut of one of the world's rarest insect species, Galloisiana
      sp., collected at a Mosan cave, Moonkyung, Gyungsangbook-do, South Korea. Strain
      B14(T) is a novel genus candidate of the family Enterobacteriaceae.

PMID- 23144399
TI  - Draft genome sequence of the antifungal-producing plant-benefiting bacterium
      Burkholderia pyrrocinia CH-67.
AB  - Burkholderia pyrrocinia CH-67 was isolated from forest soil as a biocontrol agent
      to be utilized in agriculture. Here, we report the 8.05-Mb draft genome sequence
      of this bacterium. Its genome contains genes involved in biosynthesis of
      secondary metabolites and plant growth promotion, which may contribute to
      probiotic effects on plants.

PMID- 23144400
TI  - Genome sequence of Rhizobium grahamii CCGE502, a broad-host-range symbiont with
      low nodulation competitiveness in Phaseolus vulgaris.
AB  - Here we present the genome sequence of Rhizobium grahamii CCGE502. R. grahamii
      groups with other newly described broad-host-range species, which are not very
      efficient Phaseolus vulgaris symbionts, with a wide geographic distribution and
      which constitutes a novel Rhizobium clade.

PMID- 23144401
TI  - Complete genome sequence of Streptococcus agalactiae GD201008-001, isolated in
      China from tilapia with meningoencephalitis.
AB  - This work describes a whole-genome sequence of Streptococcus agalactiae strain
      GD201008-001, a pathogen causing meningoencephalitis in cultural tilapia in
      China. The genome sequence provides opportunities to understand the piscine GBS
      pathogenicity and its genetic basis associated with host tropism.

PMID- 23144402
TI  - Complete genome sequence of "Candidatus Portiera aleyrodidarum" BT-QVLC, an
      obligate symbiont that supplies amino acids and carotenoids to Bemisia tabaci.
AB  - The genome of "Candidatus Portiera aleyrodidarum," the primary endosymbiont of
      the whitefly Bemisia tabaci (Mediterranean species), is reported. It presents a
      reduced genome (357 kb) encoding the capability to synthetize, or participate in
      the synthesis of, several amino acids and carotenoids, being the first insect
      endosymbiont capable of supplying carotenoids.

PMID- 23144403
TI  - Draft genome sequence of Paenisporosarcina sp. strain TG-14, a psychrophilic
      bacterium isolated from sediment-laden stratified basal ice from Taylor Glacier,
      McMurdo Dry Valleys, Antarctica.
AB  - The psychrophilic bacterium Paenisporosarcina sp. TG-14 was isolated from
      sediment-laden stratified basal ice from Taylor Glacier, McMurdo Dry Valleys,
      Antarctica. Here we report the draft genome sequence of this strain, which may
      provide useful information on the cold adaptation mechanism in extremely variable
      environments.

PMID- 23144404
TI  - Complete genome sequence of Brucella abortus 134, a biovar 1 strain isolated from
      human.
AB  - Brucella abortus is one of the common pathogens causing brucellosis in China.
      Here, we report the genome sequence of B. abortus strain 134, a strain isolated
      from a human patient and belonging to biovar 1, the most highly represented
      biovar among B. abortus strains in China.

PMID- 23144405
TI  - Draft genome sequence of the extremely halophilic archaeon Halogranum salarium B
      1T.
AB  - Halogranum salarium is an extremely halophilic archaeon isolated from evaporitic
      salt crystals and belongs to the family Halobacteriaceae. Here, we present the
      4.5-Mb draft genome sequence of the type strain (B-1(T)) of H. salarium. This is
      the first report of the draft genome sequence of a haloarchaeon in the genus
      Halogranum.

PMID- 23144406
TI  - Genome sequence of Borrelia garinii strain NMJW1, isolated from China.
AB  - We announce the draft genome sequence of Borrelia garinii strain NMJW1, isolated
      from Ixodes persulcatus in northeastern China. The 902,789-bp linear chromosome
      (28.4% GC content) contains 813 open reading frames, 33 tRNAs, and 4 complete
      rRNAs.

PMID- 23144407
TI  - Genome sequence of Mycobacterium abscessus strain M152.
AB  - Mycobacterium abscessus is an environmental bacterium with increasing clinical
      relevance. Here, we report the annotated whole-genome sequence of M. abscessus
      strain M152.

PMID- 23144408
TI  - Complete genome sequence of Corynebacterium pseudotuberculosis Cp31, isolated
      from an Egyptian buffalo.
AB  - Corynebacterium pseudotuberculosis is of major veterinary importance because it
      affects many animal species, causing economically significant livestock diseases
      and losses. Therefore, the genomic sequencing of various lines of this organism,
      isolated from different hosts, will aid in the development of diagnostic methods
      and new prevention and treatment strategies and improve our knowledge of the
      biology of this microorganism. In this study, we present the genome of C.
      pseudotuberculosis Cp31, isolated from a buffalo in Egypt.

PMID- 23144409
TI  - Complete genome sequence of Leuconostoc gelidum strain JB7, isolated from kimchi.
AB  - A strain of Leuconostoc gelidum, designated strain JB7, was isolated from kimchi,
      the representative Korean traditional fermented food. Here we announce the
      complete genome sequence of L. gelidum strain JB7, consisting of a 1,893,499-bp
      circular chromosome with a G+C content of 36.68%, and provide a description of
      its annotation.

PMID- 23144410
TI  - Genome sequence of the biocontrol agent Microbacterium barkeri strain 2011-R4.
AB  - Microbacterium barkeri strain 2011-R4 is a Gram-positive epiphyte which has been
      confirmed as a biocontrol agent against several plant pathogens in our previous
      studies. Here, we present the draft genome sequence of this strain, which was
      isolated from the rice rhizosphere in Tonglu city, Zhejiang province, China.

PMID- 23144411
TI  - Draft genome sequence of Bacillus pumilus BA06, a producer of alkaline serine
      protease with leather-dehairing function.
AB  - Bacillus pumilus BA06 was isolated from the proteinaceous soil and produced an
      extracellular alkaline protease with leather-dehairing function. The genome of
      BA06 was sequenced. The comparative genome analysis indicated that strain BA06 is
      different in genome from the other B. pumilus strains, with limited insertions,
      deletions, and rearrangements.

PMID- 23144412
TI  - Genome sequence of "Candidatus Microthrix parvicella" Bio17-1, a long-chain-fatty
      acid-accumulating filamentous actinobacterium from a biological wastewater
      treatment plant.
AB  - "Candidatus Microthrix" bacteria are deeply branching filamentous actinobacteria
      which occur at the water-air interface of biological wastewater treatment plants,
      where they are often responsible for foaming and bulking. Here, we report the
      first draft genome sequence of a strain from this genus: "Candidatus Microthrix
      parvicella" strain Bio17-1.

PMID- 23144413
TI  - Complete genome sequence of Leuconostoc carnosum strain JB16, isolated from
      kimchi.
AB  - Leuconostoc carnosum strain JB16 was isolated from kimchi, the traditional Korean
      fermented food. Here, we report the complete genome sequence of L. carnosum
      strain JB16, consisting of a 1,645,096-bp circular chromosome with a G+C content
      of 37.24% and four plasmids.

PMID- 23144414
TI  - Complete genome sequence of Alcanivorax dieselolei type strain B5.
AB  - Alcanivorax dieselolei B5(T) was isolated from oil-contaminated surface water of
      the Bohai Sea of China and characterized by the efficient degradation of alkane
      (C(5)-C(36)). Here we report the complete genome of B5(T) and genes associated
      with alkane degradation.

PMID- 23144415
TI  - Complete genome sequence of Burkholderia phenoliruptrix BR3459a (CLA1), a heat
      tolerant, nitrogen-fixing symbiont of Mimosa flocculosa.
AB  - The genus Burkholderia represents a challenge to the fields of taxonomy and
      phylogeny and, especially, to the understanding of the contrasting roles as
      either opportunistic pathogens or bacteria with biotechnological potential. Few
      genomes of nonpathogenic strains, especially of diazotrophic symbiotic bacteria,
      have been sequenced to improve understanding of the genus. Here, we contribute
      with the complete genome sequence of Burkholderia phenoliruptrix strain BR3459a
      (CLA1), an effective diazotrophic symbiont of the leguminous tree Mimosa
      flocculosa Burkart, which is endemic to South America.

PMID- 23144416
TI  - Complete genome sequence of the pyrene-degrading bacterium Cycloclasticus sp.
      strain P1.
AB  - Cycloclasticus sp. strain P1 was isolated from deep-sea sediments of the Pacific
      Ocean and characterized as a unique bacterium in the degradation of pyrene, a
      four-ring polycyclic aromatic hydrocarbon (PAH). Here we report the complete
      genome of P1 and genes associated with PAH degradation.

PMID- 23144418
TI  - Complete genome sequence of Brucella canis strain 118, a strain isolated from
      canine.
AB  - Brucella canis infects several species of animals, and canine is the preferred
      host. Genome sequences of strains from different hosts are valuable for
      comparative analysis of host adaptation and microevolution. Here, we report the
      genome sequence of Brucella canis strain 118, a strain isolated from canine.

PMID- 23144417
TI  - Genome sequences of the primary endosymbiont "Candidatus Portiera aleyrodidarum"
      in the whitefly Bemisia tabaci B and Q biotypes.
AB  - "Candidatus Portiera aleyrodidarum" is the obligate primary endosymbiotic
      bacterium of whiteflies, including the sweet potato whitefly Bemisia tabaci, and
      provides essential nutrients to its host. Here we report two complete genome
      sequences of this bacterium from the B and Q biotypes of B. tabaci.

PMID- 23144419
TI  - Genome sequence of Roseomonas sp. strain B5, a quorum-quenching N-acylhomoserine
      lactone-degrading bacterium isolated from Malaysian tropical soil.
AB  - Roseomonas sp. strain B5 was isolated from Malaysian tropical soil that showed N
      acylhomoserine lactone degradation. This is the first genome announcement of a
      member from the genus of Roseomonas and the first report on the quorum-quenching
      activity of Roseomonas spp.

PMID- 23144420
TI  - Draft genome sequence of Oceaniovalibus guishaninsula JLT2003T.
AB  - Oceaniovalibus guishaninsula, as a representative of a new genus within the
      family Rhodobacteraceae, was isolated from surface seawater that was sulfidic.
      Here, we present the draft genome sequence of the type strain, JLT2003(T).

PMID- 23144421
TI  - Draft genome sequence of the thermophilic bacterium Anoxybacillus kamchatkensis
      G10.
AB  - Anoxybacillus kamchatkensis G10 is a spore-forming thermophilic bacterium
      isolated from a hot spring in Indonesia. Here, we report the draft genome
      sequence of A. kamchatkensis G10 that may reveal insights into aerobic/anaerobic
      metabolisms and carbon utilization in moderate thermophiles.

PMID- 23144422
TI  - Complete genome sequence of Actinobacillus suis H91-0380, a virulent serotype O2
      strain.
AB  - Here, we report the first complete genome sequence of Actinobacillus suis, an
      important opportunistic pathogen of swine. By comparing the genome sequence of A.
      suis with those of other members of the family Pasteurellaceae, we hope to better
      understand the role of these organisms in health and disease in swine.

PMID- 23144423
TI  - Genome sequence of Pedobacter arcticus sp. nov., a sea ice bacterium isolated
      from tundra soil.
AB  - Pedobacter arcticus sp. nov. was originally isolated from tundra soil collected
      from Ny-Alesund, in the Arctic region of Norway. It is a Gram-negative bacterium
      which shows bleb-shaped appendages on the cell surface. Here, we report the draft
      annotated genome sequence of Pedobacter arcticus sp. nov., which belongs to the
      genus Pedobacter.

PMID- 23144424
TI  - Genome sequence of Exiguobacterium antarcticum B7, isolated from a biofilm in
      Ginger Lake, King George Island, Antarctica.
AB  - Exiguobacterium antarcticum is a psychotropic bacterium isolated for the first
      time from microbial mats of Lake Fryxell in Antarctica. Many organisms of the
      genus Exiguobacterium are extremophiles and have properties of biotechnological
      interest, e.g., the capacity to adapt to cold, which make this genus a target for
      discovering new enzymes, such as lipases and proteases, in addition to improving
      our understanding of the mechanisms of adaptation and survival at low
      temperatures. This study presents the genome of E. antarcticum B7, isolated from
      a biofilm sample of Ginger Lake on King George Island, Antarctic peninsula.

PMID- 23144425
TI  - Genome sequence of multidrug-resistant Escherichia coli EC302/04, isolated from a
      human tracheal aspirate.
AB  - Escherichia coli is an important etiologic agent of lower respiratory tract
      infections (LRTI). Multidrug-resistant E. coli EC302/04 was isolated from a
      tracheal aspirate, and its genome sequence is expected to provide insights into
      antimicrobial resistance as well as adaptive and virulence mechanisms of E. coli
      involved in LRTI.

PMID- 23144426
TI  - Draft genome sequence of high-melanin-yielding Aeromonas media strain WS.
AB  - We sequenced the genome of the high-melanin-yielding Aeromonas media strain WS
      and then analyzed genes potentially involved in melanin formation. The 4.2-Mb
      draft genome carries multiple genes responsible for pyomelanin synthesis and
      other candidate genes identified in our separate study, which have no homolog in
      other strains of Aeromonas species.

PMID- 23144427
TI  - Draft genome sequence of Salimicrobium sp. strain MJ3, isolated from Myulchi
      Jeot, Korean fermented seafood.
AB  - Salimicrobium sp. strain MJ3 was isolated from myulchi-jeot, traditional
      fermented seafood made from anchovy in South Korea. Here we announce the draft
      genome sequence of Salimicrobium sp. MJ3 with 2,717,782 bp, which consists of 45
      contigs (>500 bp in size), and provide a description of their annotation.

PMID- 23144428
TI  - Genome sequence of Stenotrophomonas maltophilia S028, an isolate harboring the
      AmpR-L2 resistance module.
AB  - Multidrug-resistant Stenotrophomonas maltophilia has emerged as an important
      cause of nosocomial infections, which is attributable mainly to the production of
      diverse beta-lactamases by S. maltophilia. The L2 beta-lactamase mediated by the
      AmpR-L2 module is the most represented lactamase. Here, we announce the genome
      sequence of S028, an isolate harboring the AmpR-L2 module.

PMID- 23144429
TI  - Complete genome sequence of Brucella canis BCB018, a strain isolated from a human
      patient.
AB  - Brucella canis is considered a rare cause of human brucellosis because of
      difficulties in presumptive diagnosis and underestimation of the incidence. Here,
      we report the draft genome sequence of a Brucella canis isolate, BCB018, isolated
      from a human patient, providing precious resources for comparative genomics
      analysis of Brucella field strains.

PMID- 23144430
TI  - The local peripheral antihyperalgesic effect of levetiracetam and its mechanism
      of action in an inflammatory pain model.
AB  - BACKGROUND: We have recently shown that levetiracetam, administered systemically,
      exerts an antihyperalgesic effect in a rat inflammatory pain model. In this
      study, we examined whether levetiracetam has local peripheral
      antihyperalgesic/anti-edematous effects in the same model of localized
      inflammation and whether opioidergic, adrenergic, purinergic, 5-HTergic, and
      GABAergic receptors are involved in its antihyperalgesic action. METHODS: Rats
      were intraplantarly (IPL) injected with carrageenan. A paw pressure test was used
      to determine the effect/s of (a) levetiracetam when applied IPL, on carrageenan
      induced hyperalgesia, and (b) naloxone (a nonselective opioid receptor
      antagonist), CTAP (a selective MU-opioid receptor antagonist); yohimbine (a
      selective alpha(2)-adrenoceptor antagonist), BRL 44408 (a selective alpha(2A)
      adrenoceptor antagonist), MK-912 (a selective alpha(2C)-adrenoceptor antagonist);
      caffeine (a nonselective adenosine receptor antagonist), DPCPX (a selective
      adenosine A(1) receptor antagonist); methysergide (a nonselective 5-HT receptor
      antagonist), GR 127935 (a selective 5-HT(1B/1D) receptor antagonist); and
      bicuculline (a selective GABA(A) receptor antagonist), all applied IPL, on the
      levetiracetam-induced antihyperalgesia. Moreover, levetiracetam's influence on
      paw inflammatory edema was measured by plethysmometry. RESULTS: Levetiracetam
      (200-1000 nmol/paw) produced a significant dose-dependent reduction of the paw
      inflammatory hyperalgesia and edema induced by carrageenan. Naloxone (75-300
      nmol/paw), CTAP (1-5 nmol/paw); yohimbine (130-520 nmol/paw), BRL 44408 (50-200
      nmol/paw), MK-912 (5-20 nmol/paw); caffeine (500-1500 nmol/paw), DPCPX (3-30
      nmol/paw); methysergide (10-100 nmol/paw) and GR 127935 (50-200 nmol/paw); but
      not bicuculline (400 nmol/paw), significantly depressed the antihyperalgesic
      effects of levetiracetam (1000 nmol/paw). The effects of levetiracetam and
      antagonists were attributed to local peripheral effects because they were not
      observed after administration into the contralateral hind-paw. CONCLUSIONS: Our
      results show that levetiracetam produces local peripheral antihyperalgesic and
      anti-edematous effects in a rat model of localized inflammation. Antihyperalgesia
      is at least in part mediated by peripheral MU-opioid, alpha2A,C-adrenergic, A1
      adenosine, and 5-HT1B/1D receptors, but not by GABAA receptors. These findings
      could contribute toward a better understanding of the analgesic effects of
      levetiracetam, and improved treatments of inflammatory pain with a lower
      incidence of systemic side effects and drug interactions of levetiracetam.

PMID- 23144431
TI  - Bariatric surgery with operating room teams that stayed fixed during the day: a
      multicenter study analyzing the effects on patient outcomes, teamwork and safety
      climate, and procedure duration.
AB  - BACKGROUND: Bariatric surgery durations vary considerably because of differences
      in surgical procedures and patient factors. We studied the effects on patient
      outcomes, teamwork and safety climate, and procedure durations resulting from
      working with operating room (OR) teams that remain fixed for the day instead of
      OR teams that vary during the day. METHODS: Data were collected in 2 general
      teaching hospitals, consisting of patientrelated demographic and intraoperative
      data and of staffrelated survey data on team work and safety climate. The
      procedure durations of fixed and conventional OR teams were analyzed by
      comparison of means tests and by regression methods to control for the effects of
      surgeon, surgical experience, and procedure type. RESULTS: For both hospitals, we
      obtained the following 4 results for working on bariatric procedures with OR
      teams that remained fixed for the day. First, patient outcomes did not worsen.
      Second, teamwork and safety climate (both measured on a 5-point scale) improved
      significantly, for teamwork + 0.86 (95% confidence interval [CI], 0.54 to 1.18)
      and for safety climate + 0.75 (95% CI, 0.40 to 1.11). Third, the procedures were
      performed significantly faster, as both the mean and the SD of procedure
      durations decreased. After correcting for learning effects, the average reduction
      of durations was 10.8% (99% CI, 5.0% to 15.3%, or 4 to 13 minutes). This gain was
      mainly realized for surgical time (12%; 99% CI, 5% to 18%, or 3 to 11 minutes).
      The effect on peripheral time, defined as procedure time minus surgical time, is
      not significant (3%; 99% CI, -6% to 12%, or -1 to 3 minutes). Fourth, additional
      gains were obtained by performing the same type of procedure multiple times
      within the same day (5% per every next procedure of the same type; 99% CI, 3% to
      7%, or 3 to 6 minutes). CONCLUSIONS: Working with fixed teams in bariatric
      surgery reduced procedure durations and improved teamwork and safety climate,
      without adverse effects on patient outcomes.

PMID- 23144432
TI  - Special Article: Ronald D. Miller: tribute to a past editor-in-chief.
AB  - For anesthesiologists around the world who have practiced or trained in the past
      4 decades, the name Ronald Miller, MD, has been synonymous with a commitment to
      excellence that has been evident in all aspects of his remarkable career as a
      distinguished clinician-scientist, editor, writer, and educator. Dr. Miller's
      contributions as Editor-in-Chief of Anesthesia & Analgesia (1991-2006) have
      stimulated this salutation of his career and of his influence on transforming the
      Journal.

PMID- 23144433
TI  - Special article: Laurette McMechan (1878-1970): "mother of anesthetists".
AB  - Laurette van Varseveld McMechan (1878-1970) was married to Francis Hoeffer
      McMechan (1879-1939), who organized the International Anesthesia Research Society
      and was the editor of the first journal for physician and dentist anesthetists.
      Although she was not a physician, she made vital contributions to the development
      of worldwide organized anesthesia and its journals. These were most evident after
      her husband became severely disabled in 1911, when Laurette McMechan worked
      closely with him on his efforts to organize the practice of anesthesiology and
      create a scholarly journal for the specialty. After his death, she continued to
      serve our profession for another 17 years, serving as assistant executive
      secretary-editor of the International Anesthesia Research Society and its
      journal, Current Researches in Anesthesia and Analgesia. Her life was dedicated
      to the profession of anesthesia. A memorial tribute labeled her "the mother of
      anesthetists," a title she deserved.

PMID- 23144434
TI  - Special Article: recovering the long-lost trophy awarded in 1937 to the founders
      McMechan by the International Anesthesia Research Society.

PMID- 23144435
TI  - Review article: cerebral near-infrared spectroscopy in adults: a work in
      progress.
AB  - Near-infrared spectroscopy (NIRS) has potential as a noninvasive brain monitor
      across a spectrum of disorders. In the last decade, there has been a rapid
      expansion of clinical experience using NIRS to monitor cerebral oxygenation, and
      there is some evidence that NIRS-guided brain protection protocols might lead to
      a reduction in perioperative neurologic complications after cardiac surgery.
      However, there are no data to support the wider application of NIRS during
      routine surgery under general anesthesia, and its application in brain injury,
      where it might be expected to have a key monitoring role, is undefined. Although
      increasingly sophisticated apparatuses, including broadband and time-resolved
      spectroscopy systems, provide insights into the potential of NIRS to measure
      regional cerebral oxygenation, hemodynamics, and metabolism in real-time, these
      innovations have yet to translate into effective monitor-guided brain protection
      treatment strategies. NIRS has many potential advantages over other
      neuromonitoring techniques, but further investigation and technological advances
      are necessary before it can be introduced more widely into clinical practice.

PMID- 23144436
TI  - Special Article: Howard Dittrick: curator to the McMechans' legacy journal.
AB  - A noted medical historian and museum curator, Canadian American Howard Dittrick
      was a Cleveland gynecologist who served as Directing Editor of Current Researches
      in Anesthesia and Analgesia (1940-1954). In the aftermath of World War II, even
      after Congresses of Anesthetists had resumed, Dittrick and his editorial board
      allowed their yellow, then tan-covered journal, the so-called "yellow peril," to
      languish into near irrelevance.

PMID- 23144437
TI  - The accuracy of noninvasive hemoglobin monitoring using the radical-7 pulse CO
      Oximeter in children undergoing neurosurgery.
AB  - BACKGROUND: The most common method for determining the hemoglobin concentration
      is to draw blood from a patient. However, the Radical-7 Pulse CO-Oximeter (Masimo
      Corporation, Irvine, CA) can noninvasively provide continuous hemoglobin
      concentration (SpHb). In our study we compared noninvasive measurements of SpHb
      with simultaneous laboratory measurements of total hemoglobin in arterial blood
      samples taken from children (tHb). METHODS: Arterial blood samples were analyzed
      using a laboratory CO-oximeter, and SpHb was simultaneously recorded in pediatric
      patients undergoing neurosurgery. When patients met the criteria for hypovolemia,
      10 mL/kg of colloids or red blood cells were administered over 10 minutes. SpHb
      and tHb data were collected before and after intravascular volume resuscitation.
      The relationship between SpHb and tHb was assessed using a 4-quadrant plot,
      linear regression, mixed-effect model, and modified Bland-Altman analyses.
      RESULTS: One hundred nineteen paired samples were analyzed. The correlation
      coefficient between SpHb and tHb was 0.53 (P < 0.001), whereas that of change in
      SpHb versus change in tHb was 0.75 (P < 0.001). The average difference (bias)
      between tHb and SpHb was 0.90 g/dL (95% confidence interval [CI], 0.48-1.32 g/dL)
      and 1 standard deviation of the difference (sd) was 1.35 g/dL. The concordance
      rate (a measure of the number of data points that are in 1 of the 2 quadrants of
      agreement) determined using a 4-quadrant plot was 93%. The correlation
      coefficient between SpHb and tHb after intravascular volume resuscitation was
      0.58 (P < 0.001), whereas that of changes in SpHb and tHb was 0.87 (P < 0.001).
      The bias immediately after volume resuscitation was 1.18 g/dL (95% CI, 0.81-1.55
      g/dL), and sd was 1.28 g/dL with a concordance rate of 94.4%. The bias was -0.03
      g/dL when tHb was >=11 g/dL, which was significantly lower in comparison with
      biases when tHb <9 g/dL (1.24 g/dL) and tHb was 9-11 g/dL (1.17 g/dL) (P =
      0.004). CONCLUSION: The Radical-7 Pulse CO-Oximeter can be useful as a trend
      monitor in children during surgery even immediately after intravascular volume
      expanders are administered. However, it is advisable to confirm the baseline
      hemoglobin level and to consider the influence of tHb level on the bias. In
      addition, one should be cautious with regard to using SpHb alone when making
      transfusion decisions.

PMID- 23144438
TI  - The postoperative analgesic efficacy of preperitoneal continuous wound infusion
      compared to epidural continuous infusion with local anesthetics after colorectal
      cancer surgery: a randomized controlled multicenter study.
AB  - BACKGROUND: Open colorectal cancer (CRC) surgery induces severe and prolonged
      postoperative pain. The optimal method of postoperative analgesia in CRC surgery
      has not been established. We evaluated the efficacy of preperitoneal continuous
      wound infusion (CWI) of ropivacaine for postoperative analgesia after open CRC
      surgery in a multicenter randomized controlled trial. METHODS: Candidates for
      open CRC surgery randomly received preperitoneal CWI analgesia or continuous
      epidural infusion (CEI) analgesia with ropivacaine 0.2% 10 mL/h for 48 hours
      after surgery. Fifty-three patients were allocated to each group. All patients
      received patient-controlled IV morphine analgesia. RESULTS: Over the 72-hour
      period after the end of surgery, CWI analgesia was not inferior to CEI analgesia.
      The difference of the mean visual analog scale score between CEI and CWI patients
      was 1.89 (97.5% confidence interval = -0.42, 4.19) at rest and 2.76 (97.5%
      confidence interval = -2.28, 7.80) after coughing. Secondary end points, morphine
      consumption and rescue analgesia, did not differ between groups. Time to first
      flatus was 3.06 +/- 0.77 days in the CWI group and 3.61 +/- 1.41 days in the CEI
      group (P = 0.002). Time to first stool was shorter in the CWI than the CEI group
      (4.49 +/- 0.99 vs 5.29 +/- 1.62 days; P = 0.001). Mean time to hospital discharge
      was shorter in the CWI group than in the CEI group (7.4 +/- 0.41 and 8.0 +/- 0.38
      days, respectively). More patients in the CWI group reported excellent quality of
      postoperative pain control (45.3% vs 7.6%). Quality of night sleep was better
      with CWI analgesia, particularly at the postoperative 72-hour evaluation (P =
      0.009). Postoperative nausea and vomiting was significantly less frequent with
      CWI analgesia at 24 hours (P = 0.02), 48 hours (P = 0.01), and 72 hours (P =
      0.007) after surgery evaluations. CONCLUSIONS: Preperitoneal CWI analgesia with
      ropivacaine 0.2% continuous infusion at 10 mL/h during 48 hours after open CRC
      surgery provided effective postoperative pain relief not inferior to CEI
      analgesia.

PMID- 23144439
TI  - Special article: Francis Hoeffer McMechan, MD: creator of modern anesthesiology?
AB  - If one person can be credited with the creation of the infrastructure of modern
      anesthesiology, that individual would be Francis Hoeffer McMechan. He has been
      largely forgotten since his death in 1939 despite his remarkable and enduring
      accomplishments. McMechan edited the first national journal devoted to
      anesthesiology, created and managed almost all of the national and regional
      societies devoted to the specialty between 1912 and his death, and created the
      first international physician certification as a specialist in anesthesiology.
      His accomplishments are even more amazing given the severe arthritis that left
      him wheelchair-bound for almost his entire professional life and denied him the
      ability to practice anesthesia. Our specialty owes an incredible debt to this
      largely unknown and unsung hero.

PMID- 23144440
TI  - Case report: neurological complications associated with epidural analgesia in
      children: a report of 4 cases of ambiguous etiologies.
AB  - The safety and utility of pediatric epidural analgesia is well established, but
      the risk of permanent neurological injury is unknown and largely must be
      extrapolated from adult literature. In this article we present a series of 4
      cases of longterm or permanent neurologic complications associated with epidural
      analgesia. Possible mechanisms of injury and implications for practice are
      discussed.

PMID- 23144441
TI  - Reduction in intraoperative bacterial contamination of peripheral intravenous
      tubing through the use of a passive catheter care system.
AB  - BACKGROUND: Bacterial contamination of intravascular devices has been associated
      with increased morbidity and mortality in various hospital settings, including
      the perioperative environment. Catheter hub disinfection has been shown in an ex
      vivo model to attenuate intraoperative injection of bacterial organisms
      originating from the anesthesia provider's hands, providing the impetus for
      improvement in intraoperative disinfection techniques and compliance. In the
      current study, we investigated the clinical effectiveness of a new, passive
      catheter care station in reducing the incidence of bacterial contamination of
      open lumen patient IV stopcock sets. The secondary aim was to evaluate the impact
      of this novel intervention on the combined incidence of 30-day postoperative
      infections and IV catheter-associated phlebitis. METHODS: Five hundred ninety
      four operating room environments were randomized by a computer-generated list to
      receive either a novel catheter care bundle (HubScrub and DOCit) or standard caps
      in conjunction with a sterile, conventional open lumen 3-way stopcock set (24
      inch with 3-gang 4-way and T-Connector). Patients underwent general anesthesia
      according to usual practice and were followed prospectively for 30 postoperative
      days to identify the development of health care-associated infections (HCAIs)
      and/or phlebitis. The primary outcome was intraoperative bacterial contamination
      of the primary stopcock set used by the anesthesia provider(s). The secondary
      outcome was the combined incidence of 30-day postoperative infections and
      phlebitis. RESULTS: Five hundred seventy-two operating rooms were included in the
      final analysis. Study groups were comparable with no significant differences in
      patient, provider, anesthetic, or procedural characteristics. The catheter care
      station reduced the incidence of primary stopcock lumen contamination compared
      with standard caps (odds ratio [OR] 0.79, 95% confidence interval [CI] 0.63-0.98,
      P = 0.034) and was associated with a reduction in the combined incidence of HCAIs
      and IV catheter-associated phlebitis with and without adjustment for patient and
      procedural covariates (OR(adjusted) 0.589, 95% CI 0.353-0.984, P = 0.040). The
      risk-adjusted number needed to treat to eliminate 1 case of lumen contamination
      was 9 (95% CI 3.4-13.5) patients, whereas the risk-adjusted number needed to
      treat to eliminate 1 case of HCAI/catheter-associated phlebitis was 17 (95% CI
      11.8-17.9) patients. CONCLUSION: Intraoperative use of a passive catheter care
      station significantly reduced open lumen bacterial contamination and the combined
      incidence of 30-day postoperative infections and phlebitis.

PMID- 23144442
TI  - Intraoperative hydroxyethyl starch 70/0.5 is not related to acute kidney injury
      in surgical patients: retrospective cohort study.
AB  - BACKGROUND: Although high-molecular-weight hydroxyethyl starch (HES) has been
      reported to cause acute kidney injury (AKI), it is not clear whether low
      molecular-weight HES (6% HES 70/0.5) can be a risk for AKI or not. We
      hypothesized that intraoperative 6% HES 70/0.5 administration is not related to
      postoperative AKI. METHODS: A retrospective chart review was conducted to
      identify adult surgical patients with intraoperative blood loss of >=1000 mL at a
      university hospital. AKI was defined as >50% increase in serum creatinine from
      the preoperative value within 7 days after the operation according to the RIFLE
      (Risk, Injury, Failure, Loss, or End-stage kidney disease) criteria. We compared
      the incidence of AKI between patients with and without intraoperative HES
      administration. Multivariate logistic regression analysis and propensity score
      matching were also conducted to elucidate the impact of HES on postoperative AKI.
      RESULTS: Among 14,332 surgical cases, 846 patients met the inclusion criteria. In
      patients given HES (a median dose of 1000 mL, n = 635), 12.9% developed AKI,
      compared with 16.6% (-3.7%, -1.7% to 9.1%) in patients without HES (n = 211).
      Multivariate logistic regression analysis showed that HES was not an independent
      risk factor for postoperative AKI (odds ratio: 0.76, 0.48-1.21). Using the
      propensity score, 179 pairs were matched. In patients with HES, 12.3% developed
      AKI, compared with 14.5% in patients without HES (-2.2%, -4.9% to 9.3%).
      CONCLUSION: In this uncontrolled retrospective chart review, intraoperative 6%
      HES 70/0.5 in a low dose was not related to postoperative AKI in patients with
      major intraoperative blood loss. Randomized controlled trials are warranted to
      further evaluate the safety and efficacy of low-molecular-weight HES.

PMID- 23144443
TI  - Disease volumes as a marker for patient response in malignant pleural
      mesothelioma.
AB  - BACKGROUND: The goal of this study was to create a comprehensive model for
      malignant pleural mesothelioma patient survival utilizing continuous, time
      varying estimates of disease volume from computed tomography (CT) imaging in
      conjunction with clinical covariates. PATIENTS AND METHODS: Serial CT scans were
      obtained during the course of clinically standard chemotherapy for 81 patients.
      The pleural disease volume was segmented for each of the 281 CT scans, and
      relative changes in disease volume from the baseline scan were tracked over the
      course of serial follow-up imaging. A prognostic model was built using time
      varying disease volume measurements in conjunction with clinical covariates.
      RESULTS: Over the course of treatment, disease volume decreased by an average of
      19%, and median patient survival was 12.6 months from baseline. In a multivariate
      survival model, changes in disease volume were significantly associated with
      patient survival along with disease histology, Eastern Cooperative Oncology Group
      performance status, and presence of dyspnea. CONCLUSIONS: Analysis of the
      trajectories of disease volumes during chemotherapy for patients with
      mesothelioma indicates that increasing disease volume was significantly and
      independently associated with poor patient prognosis in both univariate and
      multivariate survival models.

PMID- 23144444
TI  - Association of hypomagnesemia with inferior survival in a phase III, randomized
      study of cetuximab plus best supportive care versus best supportive care alone:
      NCIC CTG/AGITG CO.17.
AB  - BACKGROUND: Cetuximab-induced hypomagnesemia has been associated with improved
      clinical outcomes in advanced colorectal cancer (CRC). We explored this
      relationship from a randomized clinical trial of cetuximab plus best supportive
      care (BSC) versus BSC alone in patients with pretreated advanced CRC. PATIENTS
      AND METHODS: Day 28 hypomagnesemia grade (0 versus >=1) and percent reduction
      (<20% versus >=20%) of Mg from baseline was correlated with outcome. RESULTS: The
      median percentage Mg reduction at day 28 was 10% (-42.4% to 63.0%) for cetuximab
      (N = 260) versus 0% (-21.1% to 25%) for BSC (N = 251) [P < 0.0001]. Grade >=1
      hypomagnesemia and >=20% reduction from baseline at day 28 were associated with
      worse overall survival (OS) [hazard ratio, HR 1.61 (95% CI 1.12-2.33), P = 0.01
      and 2.08 (95% CI 1.32-3.29), P = 0.002, respectively] in multivariate analysis
      including grade of rash (0-1 versus 2+). Dyspnea (grade >=3) was more common in
      patients with >=20% versus < 20% Mg reduction (68% versus 45%; P = 0.02) and
      grade 3/4 anorexia were higher in patients with grade >=1 hypomagnesemia (81%
      versus 63%; P = 0.02). CONCLUSIONS: In contrast to prior reports, cetuximab
      induced hypomagnesemia was associated with poor OS, even after adjustment for
      grade of rash.

PMID- 23144445
TI  - A 2-year randomised, double-blind, placebo-controlled, multicentre study of oral
      selective iNOS inhibitor, cindunistat (SD-6010), in patients with symptomatic
      osteoarthritis of the knee.
AB  - OBJECTIVE: To determine if inhibition of inducible nitric oxide synthase (iNOS)
      with cindunistat hydrochloride maleate slows progression of osteoarthritis (OA)  
      METHODS:  This 2-year, multinational, double-blind, placebo-controlled trial
      enrolled patients with symptomatic knee OA (Kellgren and Lawrence Grade (KLG) 2
      or 3). Standard OA therapies were permitted throughout. Patients were randomly
      assigned to cindunistat (50 or 200 mg/day) or placebo. Randomisation was
      stratified by KLG. Radiographs to assess joint space narrowing (JSN) were
      acquired using the modified Lyon-schuss protocol at baseline, week 48 and 96.
      RESULTS: Of 1457 patients (50 mg/day, n=485; 200 mg/day, n=486; placebo, n=486),
      1048 (71.9%) completed the study. Patients were predominantly women; 56% had
      KLG3. The primary analysis did not demonstrate superiority of cindunistat versus
      placebo for rate of change in JSN. In KLG2 patients, JSN after 48 weeks was lower
      with cindunistat 50 mg/day versus placebo (p=0.032). Least-squares mean+/-SE JSN
      with cindunistat 50 mg/day ( -0.048+/-0.028 mm) and 200 mg/day (-0.062+/-0.028
      mm) were 59.9% (95% CI 6.8% to 106.9%) and 48.7% (95% CI -8.4% to 93.9%) of
      placebo, improvement was not maintained at 96 weeks. No improvement was observed
      for KLG3 patients at either time-point. Cindunistat did not improve joint pain or
      function, but was generally well tolerated. CONCLUSIONS: Cindunistat (50 or 200
      mg/day) did not slow the rate of JSN versus placebo. After 48-weeks, KLG2
      patients showed less JSN; however, the improvement was not sustained at 96-weeks.
      iNOS inhibition did not slow OA progression in KLG3 patients.   CLINICAL TRIAL
      LISTING:  NCT00565812.

PMID- 23144447
TI  - Statins do not influence clinical response and B cell depletion after rituximab
      treatment in rheumatoid arthritis.

PMID- 23144446
TI  - Blocking the effects of interleukin-6 in rheumatoid arthritis and other
      inflammatory rheumatic diseases: systematic literature review and meta-analysis
      informing a consensus statement.
AB  - BACKGROUND: Suppression of the immunoinflammatory cascade by targeting
      interleukin 6 (IL-6) mediated effects constitutes a therapeutic option for
      chronic inflammatory diseases. Tocilizumab is the only IL-6 inhibitor (IL-6i)
      licensed for rheumatoid arthritis (RA) and juvenile idiopathic arthritis (JIA),
      but also other agents targeting either IL-6 or its receptor are investigated in
      various indications. OBJECTIVE: To review published evidence on safety and
      efficacy of IL-6i in inflammatory diseases. METHODS: We performed systematic
      literature searches in Medline and Cochrane, screened EULAR and American College
      of Rheumatology meeting-abstracts, and accessed http://www.clinicaltrials.gov.
      RESULTS: Comprehensive evidence supports the efficacy of tocilizumab in RA in
      DMARD-naive patients, and after DMARD- and TNFi-failure. Randomised comparisons
      demonstrate superiority of tocilizumab in JIA, but not ankylosing spondylitis
      (AS). Other indications are currently investigated. Additional IL-6i show similar
      efficacy; safety generally appears acceptable. CONCLUSIONS: IL-6i is effective
      and safe in RA and JIA, but not in AS. Preliminary results in other indications
      need substantiation.

PMID- 23144448
TI  - A pilot study of IL-1 inhibition in acute calcific periarthritis of the shoulder.

PMID- 23144450
TI  - Long-term safety of pegloticase in chronic gout refractory to conventional
      treatment.
AB  - OBJECTIVE: To evaluate the long-term safety (up to 3 years) of treatment with
      pegloticase in patients with refractory chronic gout. METHODS: This open-label
      extension (OLE) study was conducted at 46 sites in the USA, Canada and Mexico.
      Patients completing either of two replicate randomised placebo-controlled 6-month
      trials received pegloticase 8 mg every 2 weeks (biweekly) or every 4 weeks
      (monthly). Safety was evaluated as the primary outcome, with special interest in
      gout flares and infusion-related reactions (IRs). Secondary outcomes included
      urate-lowering and clinical efficacy. RESULTS: Patients (n=149) received a mean+/
      SD of 28+/-18 pegloticase infusions and were followed for a mean of 25+/-11
      months. Gout flares and IRs were the most frequently reported adverse events;
      these were least common in patients with a sustained urate-lowering response to
      treatment and those receiving biweekly treatment. In 10 of the 11 patients with a
      serious IR, the event occurred when uric acid exceeded 6 mg/dl. Plasma and serum
      uric acid levels remained <6 mg/dl in most randomised controlled trial (RCT)
      defined pegloticase responders throughout the OLE study and were accompanied by
      sustained and progressive improvements in tophus resolution and flare incidence.
      CONCLUSIONS: The safety profile of long-term pegloticase treatment was consistent
      with that observed during 6 months of RCT treatment; no new safety signals were
      identified. Improvements in clinical status, in the form of flare and tophus
      reduction initiated during RCT pegloticase treatment in patients maintaining goal
      range urate-lowering responses were sustained or advanced during up to 2.5 years
      of additional treatment.

PMID- 23144449
TI  - Hydroxychloroquine in systemic lupus erythematosus: results of a French
      multicentre controlled trial (PLUS Study).
AB  - INTRODUCTION: Hydroxychloroquine (HCQ) is an important medication for treating
      systemic lupus erythematosus (SLE). Its blood concentration ([HCQ]) varies widely
      between patients and is a marker and predictor of SLE flares. This prospective
      randomised, double-blind, placebo-controlled, multicentre study sought to compare
      standard and adjusted HCQ dosing schedules that target [HCQ] >=1000 ng/ml to
      reduce SLE flares. PATIENTS AND METHODS: [HCQ] was measured in 573 patients with
      SLE (stable disease and SELENA-SLEDAI<=12) treated with HCQ for at least 6
      months. Patients with [HCQ] from 100 to 750 ng/ml were randomised to one of two
      treatment groups: no daily dose change (group 1) or increased HCQ dose to achieve
      the target [HCQ] (group 2). The primary end point was the number of patients with
      flares during 7 months of follow-up. RESULTS: Overall, mean [HCQ] was 918+/-451
      ng/ml. Active SLE was less prevalent in patients with higher [HCQ]. A total of
      171 patients were randomised and followed for 7 months. SLE flare rates were
      similar in the two groups (25% in group 1 vs 27.6% in group 2; p=0.7), but a
      significant spontaneous increase in [HCQ] in both groups between inclusion and
      randomisation strongly suggested improved treatment adherence. Patients at the
      therapeutic target throughout follow-up tended to have fewer flares than those
      with low [HCQ] (20.5% vs 35.1%, p=0.12). CONCLUSIONS: Although low [HCQ] is
      associated with higher SLE activity, adapting the HCQ dose did not reduce SLE
      flares over a 7-month follow-up.

PMID- 23144451
TI  - Rescue of PINK1 protein null-specific mitochondrial complex IV deficits by
      ginsenoside Re activation of nitric oxide signaling.
AB  - PINK1, linked to familial Parkinson's disease, is known to affect mitochondrial
      function. Here we identified a novel regulatory role of PINK1 in the maintenance
      of complex IV activity and characterized a novel mechanism by which NO signaling
      restored complex IV deficiency in PINK1 null dopaminergic neuronal cells. In
      PINK1 null cells, levels of specific chaperones, including Hsp60, leucine-rich
      pentatricopeptide repeat-containing (LRPPRC), and Hsp90, were severely decreased.
      LRPPRC and Hsp90 were found to act upstream of Hsp60 to regulate complex IV
      activity. Specifically, knockdown of Hsp60 resulted in a decrease in complex IV
      activity, whereas antagonistic inhibition of Hsp90 by 17-(allylamino)
      geldanamycin decreased both Hsp60 and complex IV activity. In contrast,
      overexpression of the PINK1-interacting factor LRPPRC augmented complex IV
      activity by up-regulating Hsp60. A similar recovery of complex IV activity was
      also induced by coexpression of Hsp90 and Hsp60. Drug screening identified
      ginsenoside Re as a compound capable of reversing the deficit in complex IV
      activity in PINK1 null cells through specific increases of LRPPRC, Hsp90, and
      Hsp60 levels. The pharmacological effects of ginsenoside Re could be reversed by
      treatment of the pan-NOS inhibitor L-NG-Nitroarginine Methyl Ester (L-NAME) and
      could also be reproduced by low-level NO treatment. These results suggest that
      PINK1 regulates complex IV activity via interactions with upstream regulators of
      Hsp60, such as LRPPRC and Hsp90. Furthermore, they demonstrate that treatment
      with ginsenoside Re enhances functioning of the defective PINK1-Hsp90/LRPPRC
      Hsp60-complex IV signaling axis in PINK1 null neurons by restoring NO levels,
      providing potential for new therapeutics targeting mitochondrial dysfunction in
      Parkinson's disease.

PMID- 23144452
TI  - Conjugated linoleic acid is a preferential substrate for fatty acid nitration.
AB  - The oxidation and nitration of unsaturated fatty acids by oxides of nitrogen
      yield electrophilic derivatives that can modulate protein function via post
      translational protein modifications. The biological mechanisms accounting for
      fatty acid nitration and the specific structural characteristics of products
      remain to be defined. Herein, conjugated linoleic acid (CLA) is identified as the
      primary endogenous substrate for fatty acid nitration in vitro and in vivo,
      yielding up to 10(5) greater extent of nitration products as compared with bis
      allylic linoleic acid. Multiple enzymatic and cellular mechanisms account for CLA
      nitration, including reactions catalyzed by mitochondria, activated macrophages,
      and gastric acidification. Nitroalkene derivatives of CLA and their metabolites
      are detected in the plasma of healthy humans and are increased in tissues
      undergoing episodes of ischemia reperfusion. Dietary CLA and nitrite
      supplementation in rodents elevates NO(2)-CLA levels in plasma, urine, and
      tissues, which in turn induces heme oxygenase-1 (HO-1) expression in the colonic
      epithelium. These results affirm that metabolic and inflammatory reactions yield
      electrophilic products that can modulate adaptive cell signaling mechanisms.

PMID- 23144453
TI  - Role of the wrist domain in the response of the epithelial sodium channel to
      external stimuli.
AB  - The epithelial Na(+) channel (ENaC) is regulated by a variety of external factors
      that alter channel activity by inducing conformational changes within its large
      extracellular region that are transmitted to the gate. The wrist domain consists
      of small linkers connecting the extracellular region to the transmembrane
      domains, where the channel pore and gate reside. We employed site-directed
      mutagenesis combined with two-electrode voltage clamp to investigate the role of
      the wrist domain in channel gating in response to extracellular factors. Channel
      inhibition by external Na(+) was reduced by selected mutations within the wrist
      domain of the alpha subunit, likely reflecting an increase in channel open
      probability. The most robust changes were observed when Cys was introduced at
      alphaPro-138 and alphaSer-568, sites immediately adjacent to the palm domain. In
      addition, one of these Cys mutants exhibited an enhanced response to shear
      stress. In the context of channels that have a low open probability due to
      retention of an inhibitory tract, the response to external Na(+) was reduced by
      Cys substitutions at both alphaPro-138 and alphaSer-568. We observed a
      significant correlation between changes in channel inhibition by external Na(+)
      and the relative response to shear stress for the alpha subunit mutants that were
      examined. Mutants that exhibited reduced inhibition by external Na(+) also showed
      an enhanced response to shear stress. Together, our data suggest that the wrist
      domain has a role in modulating the channel's response to external stimuli.

PMID- 23144454
TI  - Cortactin controls surface expression of the voltage-gated potassium channel
      K(V)10.1.
AB  - K(V)10.1 is a voltage-gated potassium channel aberrantly expressed in many cases
      of cancer, and participates in cancer initiation and tumor progression. Its
      action as an oncoprotein can be inhibited by a functional monoclonal antibody,
      indicating a role for channels located at the plasma membrane, accessible to the
      antibody. Cortactin is an actin-interacting protein implicated in cytoskeletal
      architecture and often amplified in several types of cancer. In this study, we
      describe a physical and functional interaction between cortactin and K(V)10.1.
      Binding of these two proteins occurs between the C terminus of K(V)10.1 and the
      proline-rich domain of cortactin, regions targeted by many post-translational
      modifications. This interaction is specific for K(V)10.1 and does not occur with
      K(V)10.2. Cortactin controls the abundance of K(V)10.1 at the plasma membrane and
      is required for functional expression of K(V)10.1 channels.

PMID- 23144455
TI  - Retinoid binding properties of nucleotide binding domain 1 of the Stargardt
      disease-associated ATP binding cassette (ABC) transporter, ABCA4.
AB  - The retina-specific ATP binding cassette transporter, ABCA4 protein, is
      associated with a broad range of inherited macular degenerations, including
      Stargardt disease, autosomal recessive cone rod dystrophy, and fundus
      flavimaculatus. In order to understand its role in retinal transport in rod out
      segment discs, we have investigated the interactions of the soluble domains of
      ABCA4 with both 11-cis- and all-trans-retinal. Using fluorescence anisotropy
      based binding analysis and recombinant polypeptides derived from the amino acid
      sequences of the four soluble domains of ABCA4, we demonstrated that the
      nucleotide binding domain 1 (NBD1) specifically bound 11-cis-retinal. Its
      affinity for all-trans-retinal was markedly reduced. Stargardt disease-associated
      mutations in this domain resulted in attenuation of 11-cis-retinal binding.
      Significant differences in 11-cis-retinal binding affinities were observed
      between NBD1 and other cytoplasmic and lumenal domains of ABCA4. The results
      suggest a possible role of ABCA4 and, in particular, the NBD1 domain in 11-cis
      retinal binding. These results also correlate well with a recent report on the in
      vivo role of ABCA4 in 11-cis-retinal transport.

PMID- 23144456
TI  - Lipid raft-dependent endocytosis of close homolog of adhesion molecule L1 (CHL1)
      promotes neuritogenesis.
AB  - CHL1 plays a dual role by either promoting or inhibiting neuritogenesis. We
      report here that neuritogenesis-promoting ligand-dependent cell surface
      clustering of CHL1 induces palmitoylation and lipid raft-dependent endocytosis of
      CHL1. We identify betaII spectrin as a binding partner of CHL1, and we show that
      partial disruption of the complex between CHL1 and betaII spectrin accompanies
      CHL1 endocytosis. Inhibition of the association of CHL1 with lipid rafts by
      pharmacological disruption of lipid rafts or by mutation of cysteine 1102 within
      the intracellular domain of CHL1 reduces endocytosis of CHL1. Endocytosis of CHL1
      is also reduced by nifedipine, an inhibitor of the L-type voltage-dependent
      Ca(2+) channels. CHL1-dependent neurite outgrowth is reduced by inhibitors of
      lipid raft assembly, inhibitors of voltage-dependent Ca(2+) channels, and
      overexpression of CHL1 with mutated cysteine Cys-1102. Our results suggest that
      ligand-induced and lipid raft-dependent regulation of CHL1 adhesion via Ca(2+)
      dependent remodeling of the CHL1-betaII spectrin complex and CHL1 endocytosis are
      required for CHL1-dependent neurite outgrowth.

PMID- 23144457
TI  - Differential arabinan capping of lipoarabinomannan modulates innate immune
      responses and impacts T helper cell differentiation.
AB  - Toll-like receptors (TLRs) recognize pathogens by interacting with pathogen
      associated molecular patterns, such as the phosphatidylinositol-based
      lipoglycans, lipomannan (LM) and lipoarabinomannan (LAM). Such structures are
      present in several pathogens, including Mycobacterium tuberculosis, being
      important for the initiation of immune responses. It is well established that the
      interaction of LM and LAM with TLR2 is a process dependent on the structure of
      the ligands. However, the implications of structural variations on TLR2 ligands
      for the development of T helper (Th) cell responses or in the context of in vivo
      responses are less studied. Herein, we used Corynebacterium glutamicum as a
      source of lipoglycan intermediates for host interaction studies. In this study,
      we have deleted a putative glycosyltransferase, NCgl2096, from C. glutamicum and
      found that it encodes for a novel alpha(1->2)arabinofuranosyltransferase, AftE.
      Biochemical analysis of the lipoglycans obtained in the presence (wild type) or
      absence of NCgl2096 showed that AftE is involved in the biosynthesis of singular
      arabinans of LAM. In its absence, the resulting molecule is a hypermannosylated
      (hLM) form of LAM. Both LAM and hLM were recognized by dendritic cells, mainly
      via TLR2, and triggered the production of several cytokines. hLM was a stronger
      stimulus for in vitro cytokine production and, as a result, a more potent inducer
      of Th17 responses. In vivo data confirmed hLM as a stronger inducer of cytokine
      responses and suggested the involvement of pattern recognition receptors other
      than TLR2 as sensors for lipoglycans.

PMID- 23144458
TI  - Canonical transient receptor potential channel 2 (TRPC2) as a major regulator of
      calcium homeostasis in rat thyroid FRTL-5 cells: importance of protein kinase C
      delta (PKCdelta) and stromal interaction molecule 2 (STIM2).
AB  - Mammalian non-selective transient receptor potential cation channels (TRPCs) are
      important in the regulation of cellular calcium homeostasis. In thyroid cells,
      including rat thyroid FRTL-5 cells, calcium regulates a multitude of processes.
      RT-PCR screening of FRTL-5 cells revealed the presence of TRPC2 channels only.
      Knockdown of TRPC2 using shRNA (shTRPC2) resulted in decreased ATP-evoked calcium
      peak amplitude and inward current. In calcium-free buffer, there was no
      difference in the ATP-evoked calcium peak amplitude between control cells and
      shTRPC2 cells. Store-operated calcium entry was indistinguishable between the two
      cell lines. Basal calcium entry was enhanced in shTRPC2 cells, whereas the level
      of PKCbeta1 and PKCdelta, the activity of sarco/endoplasmic reticulum Ca(2+)
      ATPase, and the calcium content in the endoplasmic reticulum were decreased.
      Stromal interaction molecule (STIM) 2, but not STIM1, was arranged in puncta in
      resting shTRPC2 cells but not in control cells. Phosphorylation site Orai1
      S27A/S30A mutant and non-functional Orai1 R91W attenuated basal calcium entry in
      shTRPC2 cells. Knockdown of PKCdelta with siRNA increased STIM2 punctum formation
      and enhanced basal calcium entry but decreased sarco/endoplasmic reticulum Ca(2+)
      ATPase activity in wild-type cells. Transfection of a truncated, non-conducting
      mutant of TRPC2 evoked similar results. Thus, TRPC2 functions as a major
      regulator of calcium homeostasis in rat thyroid cells.

PMID- 23144459
TI  - Characterization of patient mutations in human persulfide dioxygenase (ETHE1)
      involved in H2S catabolism.
AB  - Hydrogen sulfide (H(2)S) is a recently described endogenously produced gaseous
      signaling molecule that influences various cellular processes in the central
      nervous system, cardiovascular system, and gastrointestinal tract. The biogenesis
      of H(2)S involves the cytoplasmic transsulfuration enzymes, cystathionine beta
      synthase and gamma-cystathionase, whereas its catabolism occurs in the
      mitochondrion and couples to the energy-yielding electron transfer chain. Low
      steady-state levels of H(2)S appear to be controlled primarily by efficient
      oxygen-dependent catabolism via sulfide quinone oxidoreductase, persulfide
      dioxygenase (ETHE1), rhodanese, and sulfite oxidase. Mutations in the persulfide
      dioxgenase, i.e. ETHE1, result in ethylmalonic encephalopathy, an inborn error of
      metabolism. In this study, we report the biochemical characterization and kinetic
      properties of human persulfide dioxygenase and describe the biochemical penalties
      associated with two patient mutations, T152I and D196N. Steady-state kinetic
      analysis reveals that the T152I mutation results in a 3-fold lower activity,
      which is correlated with a 3-fold lower iron content compared with the wild-type
      enzyme. The D196N mutation results in a 2-fold higher K(m) for the substrate,
      glutathione persulfide.

PMID- 23144460
TI  - An extremely halophilic proteobacterium combines a highly acidic proteome with a
      low cytoplasmic potassium content.
AB  - Halophilic archaea accumulate molar concentrations of KCl in their cytoplasm as
      an osmoprotectant and have evolved highly acidic proteomes that function only at
      high salinity. We examined osmoprotection in the photosynthetic Proteobacteria
      Halorhodospira halophila and Halorhodospira halochloris. Genome sequencing and
      isoelectric focusing gel electrophoresis showed that the proteome of H. halophila
      is acidic. In line with this finding, H. halophila accumulated molar
      concentrations of KCl when grown in high salt medium as detected by x-ray
      microanalysis and plasma emission spectrometry. This result extends the taxonomic
      range of organisms using KCl as a main osmoprotectant to the Proteobacteria. The
      closely related organism H. halochloris does not exhibit an acidic proteome,
      matching its inability to accumulate K(+). This observation indicates recent
      evolutionary changes in the osmoprotection strategy of these organisms. Upon
      growth of H. halophila in low salt medium, its cytoplasmic K(+) content matches
      that of Escherichia coli, revealing an acidic proteome that can function in the
      absence of high cytoplasmic salt concentrations. These findings necessitate a
      reassessment of two central aspects of theories for understanding extreme
      halophiles. First, we conclude that proteome acidity is not driven by stabilizing
      interactions between K(+) ions and acidic side chains but by the need for
      maintaining sufficient solvation and hydration of the protein surface at high
      salinity through strongly hydrated carboxylates. Second, we propose that obligate
      protein halophilicity is a non-adaptive property resulting from genetic drift in
      which constructive neutral evolution progressively incorporates weakly
      stabilizing K(+)-binding sites on an increasingly acidic protein surface.

PMID- 23144461
TI  - Cyclosporin A impairs the secretion and activity of ADAMTS13 (a disintegrin and
      metalloprotease with thrombospondin type 1 repeat).
AB  - The protease ADAMTS13 (a disintegrin and metalloprotease with thrombospondin type
      1 repeat) cleaves multimers of von Willebrand factor, thus regulating platelet
      aggregation. ADAMTS13 deficiency leads to the fatal disorder thrombotic
      thrombocytopenic purpura (TTP). It has been observed that cyclosporin A (CsA)
      treatment, particularly in transplant patients, may sometimes be linked to the
      development of TTP. Until now, the reason for such a link was unclear. Here we
      provide evidence demonstrating that cyclophilin B (CypB) activity plays an
      important role in the secretion of active ADAMTS13. We found that CsA, an
      inhibitor of CypB, reduces the secretion of ADAMTS13 and leads to conformational
      changes in the protein resulting in diminished ADAMTS13 proteolytic activity. A
      direct, functional interaction between CypB (which possesses peptidyl-prolyl cis
      trans isomerase (PPIase) and chaperone functions) and ADAMTS13 is demonstrated
      using immunoprecipitation and siRNA knockdown of CypB. Finally, CypB knock-out
      mice were found to have reduced ADAMTS13 levels. Taken together, our findings
      indicate that cyclophilin-mediated activity is an important factor affecting
      secretion and activity of ADAMTS13. The large number of proline residues in
      ADAMTS13 is consistent with the important role of cis-trans isomerization in the
      proper folding of this protein. These results altogether provide a novel
      mechanistic explanation for CsA-induced TTP in transplant patients.

PMID- 23144462
TI  - Loss of Timp3 gene leads to abdominal aortic aneurysm formation in response to
      angiotensin II.
AB  - Aortic aneurysm is dilation of the aorta primarily due to degradation of the
      aortic wall extracellular matrix (ECM). Tissue inhibitors of metalloproteinases
      (TIMPs) inhibit matrix metalloproteinases (MMPs), the proteases that degrade the
      ECM. Timp3 is the only ECM-bound Timp, and its levels are altered in the aorta
      from patients with abdominal aortic aneurysm (AAA). We investigated the causal
      role of Timp3 in AAA formation. Infusion of angiotensin II (Ang II) using micro
      osmotic (Alzet) pumps in Timp3(-/-) male mice, but not in wild type control mice,
      led to adverse remodeling of the abdominal aorta, reduced collagen and elastin
      proteins but not mRNA, and elevated proteolytic activities, suggesting excess
      protein degradation within 2 weeks that led to formation of AAA by 4 weeks.
      Intriguingly, despite early up-regulation of MMP2 in Timp3(-/-)Ang II aortas,
      additional deletion of Mmp2 in these mice (Timp3(-/-)/Mmp2(-/-)) resulted in
      exacerbated AAA, compromised survival due to aortic rupture, and inflammation in
      the abdominal aorta. Reconstitution of WT bone marrow in Timp3(-/-)/Mmp2(-/-)
      mice reduced inflammation and prevented AAA in these animals following Ang II
      infusion. Treatment with a broad spectrum MMP inhibitor (PD166793) prevented the
      Ang II-induced AAA in Timp3(-/-) and Timp3(-/-)/Mmp2(-/-) mice. Our study
      demonstrates that the regulatory function of TIMP3 is critical in preventing
      adverse vascular remodeling and AAA. Hence, replenishing TIMP3, a physiological
      inhibitor of a number of metalloproteinases, could serve as a therapeutic
      approach in limiting AAA development or expansion.

PMID- 23144463
TI  - The Wnt coreceptor Ryk regulates Wnt/planar cell polarity by modulating the
      degradation of the core planar cell polarity component Vangl2.
AB  - The Wnt signaling pathways control many critical developmental and adult
      physiological processes. In vertebrates, one fundamentally important function of
      Wnts is to provide directional information by regulating the evolutionarily
      conserved planar cell polarity (PCP) pathway during embryonic morphogenesis.
      However, despite the critical roles of Wnts and PCP in vertebrate development and
      disease, little is known about the molecular mechanisms underlying Wnt regulation
      of PCP. Here, we have found that the receptor-like tyrosine kinase (Ryk), a Wnt5a
      binding protein required in axon guidance, regulates PCP signaling. We show that
      Ryk interacts with Vangl2 genetically and biochemically, and such interaction is
      potentiated by Wnt5a. Loss of Ryk in a Vangl2(+/-) background results in classic
      PCP defects, including open neural tube, misalignment of sensory hair cells in
      the inner ear, and shortened long bones in the limbs. Complete loss of both Ryk
      and Vangl2 results in more severe phenotypes that resemble the Wnt5a(-/-) mutant
      in many aspects such as shortened anterior-posterior body axis, limb, and
      frontonasal process. Our data identify the Wnt5a-binding protein Ryk as a general
      regulator of the mammalian Wnt/PCP signaling pathway. We show that Ryk transduces
      Wnt5a signaling by forming a complex with Vangl2 and that Ryk regulates PCP by at
      least in part promoting Vangl2 stability. As human mutations in WNT5A and VANGL2
      are found to cause Robinow syndrome and neural tube defects, respectively, our
      results further suggest that human mutations in RYK may also be involved in these
      diseases.

PMID- 23144464
TI  - Variability and reproducibility of circulating vitamin D in a nationwide U.S.
      population.
AB  - CONTEXT: Most studies examining associations between circulating vitamin D and
      disease are based on a single measure of vitamin D, which may not reflect levels
      over time, particularly because vitamin D concentrations vary by season. Few
      studies evaluated how well multiple 25-hydroxyvitamin D [25(OH)D] measures track
      within the same individual over time. OBJECTIVE: This study examined variability
      and reproducibility of vitamin D by evaluating repeat measurements of plasma
      25(OH)D concentrations while accounting for determinants of circulating
      concentrations including dietary supplement use and latitude of residence from a
      population of U.S. radiologic technologists. DESIGN AND PARTICIPANTS: We analyzed
      circulating 25(OH)D in blood samples taken from 538 men and women from a
      prospective, nationwide study at two time points within a 1-yr period, most
      measured in different seasons. Inter- and intra-individual variability,
      reliability coefficients, and measurement error were examined. RESULTS: The
      spearman rank correlation between two measurements of 25(OH)D concentrations was
      moderate (r = 0.75, P < 0.001) and did not vary significantly by participant
      characteristics including age, race, or latitude. The intraclass correlation
      coefficient was 0.72 (95% confidence interval = 0.68-0.76). The deattenuation
      factor of plasma 25(OH)D levels was 1.39, suggesting that a single measure of
      vitamin D on a continuous scale in regression analyses may result in attenuated
      relationships of about 40%. CONCLUSION: Our results suggest that a single blood
      sample obtained in spring or fall provides a reasonable average for 25(OH)D over
      a 1-yr period, but additional studies are needed to estimate variability and
      agreement in plasma 25(OH)D measurements over longer intervals and younger
      populations.

PMID- 23144465
TI  - Inverse correlation of miRNA and cell cycle-associated genes suggests influence
      of miRNA on benign thyroid nodule tumorigenesis.
AB  - CONTEXT: The molecular etiology of cold and benign thyroid nodules (CBTNs) is
      largely unknown. Increased thyroid epithelial cell proliferation is a hallmark of
      CBTNs. MicroRNAs (miRNAs) are prominent regulators of cell proliferation.
      OBJECTIVE: Our objective was to assess the influence of miRNAs on the increased
      proliferation and thus the molecular etiology of CBTNs. DESIGN: By using
      microarrays, we defined the molecular pattern of increased proliferation of CBTNs
      as a differential expression of cell-cycle-associated genes and miRNAs. In silico
      integration of differentially expressed miRNAs and mRNAs showed an inverse
      correlation between the expression of 59 miRNAs and 133 mRNAs. Inverse
      correlations between cell-cycle-associated genes such as CDKN1C and miR-221,
      CCND1 and miR-31, GADD45A and miR-130b, or CDKN1A and let-7f suggest a modulation
      of proliferation in CBTNs by miRNAs. Their expression was validated using
      quantitative RT-PCR and functionally characterized in cell line models. RESULTS:
      Comparative quantitative RT-PCR of 20 samples of CBTNs and their surrounding
      tissue revealed an 11-fold down-regulation of miR-31 with a 2.6-fold up
      regulation of CCND1, and a 2.6-fold up-regulation of miR-130b with a 2.3-fold
      down-regulation of its target GADD45A. Using HTori and FTC-133 cell lines, we
      analyzed proliferation, cell cycle, and apoptosis after transfection of miRNA-31
      and miRNA-130b mimic and inhibitors. Overexpression of miR-31 and the resultant
      down-regulation of CCND1 led to an arrest in the cell cycle phase G1.
      Overexpression of miR-130b led to an increase of apoptosis and necrosis within 72
      h. CONCLUSION: miR-31 and miR-130b may have an effect on tumorigenesis of CBTNs
      by regulating proliferation and apoptosis and the cell cycle through cyclin D1.

PMID- 23144466
TI  - A randomized double-blinded placebo-controlled trial on the effect of
      dehydroepiandrosterone for 16 weeks on ovarian response markers in women with
      primary ovarian insufficiency.
AB  - CONTEXT: Preliminary reports have shown encouraging effects of
      dehydroepiandrosterone (DHEA) in women with poor ovarian reserve undergoing
      assisted reproduction and primary ovarian insufficiency (POI), although data from
      randomized controlled trials are limited. The present study assesses the effect
      of DHEA on ovarian response markers in women with POI. OBJECTIVE: The objective
      of the study was to evaluate whether DHEA for 16 wk would improve ovarian
      response markers in women with POI. DESIGN: This was a randomized, double
      blinded, placebo-controlled study. SETTING: The study was conducted at a tertiary
      reproductive unit. PATIENTS: Twenty-two women with unexplained POI participated
      in the study. INTERVENTIONS: Eligible subjects were randomized into the DHEA
      group (n = 10), who received DHEA (LiveWell, 25 mg three times a day), or the
      placebo group (n = 12), who received placebo for 16 wk according to a computer
      generated randomization list. Ovarian response markers included serum anti
      mullerian hormone (AMH), FSH levels, and antral follicle count (AFC) as well as
      follicles of 10 mm or greater in diameter, and hormonal profiles were measured at
      4-wk intervals until 4 wk after completion of treatment. Any returns of menses
      and side effects from treatment were recorded. MAIN OUTCOME MEASURES: The primary
      outcome was serum AMH level. RESULTS: No significant change in serum AMH and FSH
      levels had been detected throughout the study. AFC and ovarian volume were
      significantly higher at wk 12 and 20, respectively, in the DHEA group.
      Significantly more women having at least one follicle of 10 mm or greater at wk
      12, 16, and 20 were found in the DHEA group. Serum testosterone and DHEA sulfate
      levels along with higher estradiol levels were significantly higher in the DHEA
      group. CONCLUSION: This randomized, double-blinded, placebo-controlled trial
      found higher AFC and ovarian volume at wk 12 and 20, respectively, in the DHEA
      group, although there were no significant changes in serum AMH and FSH levels.
      Further trials using a longer duration of DHEA should be considered to evaluate
      the long-term effect of DHEA in women with POI.

PMID- 23144467
TI  - Long-term fenofibrate therapy increases fibroblast growth factor 21 and retinol
      binding protein 4 in subjects with type 2 diabetes.
AB  - CONTEXT: Fenofibrate is a peroxisome proliferator-activated receptor (PPAR)-alpha
      agonist that showed beneficial effects on total cardiovascular risk in patients
      with type 2 diabetes in the Fenofibrate Intervention and Event Lowering in
      Diabetes (FIELD) study. OBJECTIVE: This study aimed to investigate the long-term
      effect of fenofibrate therapy on three novel biomarkers of cardiovascular risk,
      namely adipocyte-fatty acid-binding protein (A-FABP), fibroblast growth factor 21
      (FGF21), and retinol-binding protein 4 (RBP4), which are all downstream targets
      of PPAR-alpha or PPAR-gamma, in patients with type 2 diabetes. DESIGN, SETTING,
      AND PATIENTS: A total of 216 patients (108 in the fenofibrate group and 108 in
      the placebo group) were randomly selected from the FIELD study cohort. A-FABP,
      FGF21, and RBP4 levels were measured in serum samples at both baseline and the
      fifth year of the study. RESULTS: Relative to the placebo group, the changes of
      serum FGF21 and RBP4 levels were 85% (P < 0.001) and 10% (P = 0.032) higher in
      the fenofibrate group, respectively, over 5 yr. Fenofibrate treatment had no
      detectable effect on serum A-FABP level (P > 0.05). The effect of fenofibrate
      treatment on serum FGF21, but not RBP4, remained significant after adjusting for
      fenofibrate-induced changes in glycosylated hemoglobin, total cholesterol,
      triglycerides, apolipoprotein A-II, fibrinogen, plasma creatinine, and
      homocysteine (P = 0.002). CONCLUSIONS: Long-term fenofibrate treatment could
      increase serum FGF21 levels over 5 yr in patients with type 2 diabetes.
      Additional studies are needed to investigate the potential role of FGF21 in the
      fenofibrate-mediated reduction of cardiovascular risk.

PMID- 23144468
TI  - Maternal obesity and vitamin D sufficiency are associated with cord blood vitamin
      D insufficiency.
AB  - CONTEXT: An inverse relationship between total serum 25-hydroxyvitamin D (25-OH
      D) and increased adiposity has been established in children, adolescents, and
      adults. However, the relationship between neonatal adiposity and vitamin D status
      has not been reported. Both maternal obesity and vitamin D deficiency in
      pregnancy are common and are associated with adverse pregnancy outcomes.
      OBJECTIVE: The aim of the study was to determine the relationship between vitamin
      D levels in mothers and newborns, as influenced by maternal obesity, and evaluate
      these associations with neonatal adiposity. DESIGN, SETTING, AND PATIENTS: Sixty
      one maternal-neonatal pairs participated in this cross-sectional study at an
      academic medical center. Mothers had a prepregnancy body mass index that was
      normal or obese. OUTCOME MEASURES: Maternal and cord blood sera were assayed for
      25-OH D, and neonatal body composition was measured by air displacement
      plethysmography. RESULTS: Mothers had similar and sufficient levels of 25-OH D
      when measured at 36-38 wk gestation, irrespective of body mass index category
      (normal weight, 46.05, vs. obese, 49.84 ng/ml; P = not significant). However,
      cord blood 25-OH D was higher in neonates of normal-weight mothers compared to
      neonates of obese mothers (27.45 vs. 20.81 ng/ml; P = 0.02). The variance in cord
      blood 25-OH D was explained by four factors: maternal 25-OH D level, the presence
      of maternal obesity, maternal age, and neonatal adiposity (r(2) = 0.66).
      CONCLUSION: Obese women transfer less 25-OH D to offspring than normal-weight
      women, despite similar serum levels. Cord blood 25-OH D levels directly correlate
      to neonatal percentage body fat. These novel findings underscore the evolving
      relationships between maternal obesity, vitamin D nutritional status, and
      adiposity in the neonatal period that may influence subsequent childhood and
      adulthood vitamin D-dependent processes.

PMID- 23144470
TI  - Pseudohypoparathyroidism type 1b due to paternal uniparental disomy of chromosome
      20q.
AB  - CONTEXT: Pseudohypoparathyroidism type 1b (PHP1b) is the result of end-organ
      resistance to PTH and other hormones such as TSH in the absence of any features
      of Albright's hereditary osteodystrophy. Patients with PHP1b show imprinting
      abnormalities at the complex GNAS locus. The molecular cause of autosomal
      dominant familial PHP1b has been well-defined with identification of
      microdeletions within the GNAS locus or the nearby STX16, but the molecular
      mechanism of the GNAS imprinting defects in sporadic PHP1b cases remains elusive.
      OBJECTIVE: We investigated the underlying molecular mechanism of GNAS imprinting
      defects in two patients with sporadic PHP1b. RESULTS: We identified paternal
      uniparental disomy of the long arm of chromosome 20 (patUPD20) in two unrelated
      patients with sporadic PHP1b. This provides an explanation for the patients' GNAS
      methylation abnormalities and hormone resistance. Our data and a review of the
      six published cases of patUPD20 suggest that high birth weight and/or early-onset
      obesity and macrocephaly may also represent features of patUPD20. CONCLUSION: We
      suggest that patUPD20 should be considered in the evaluation of patients with
      sporadic PHP1b.

PMID- 23144469
TI  - Transient postnatal secretion of androgen hormones is associated with acne and
      sebaceous gland hypertrophy in early infancy.
AB  - CONTEXT: Sebaceous gland hypertrophy (SGH) and acne-like skin eruptions are
      frequent during the first months of life, yet the etiology and prevalence of
      these conditions in infants are not clear. OBJECTIVE: The objective of the study
      was to evaluate the association of postnatal androgens with SGH and acne in
      infants. DESIGN: This was a longitudinal, monthly follow-up from 1 wk (D7) to 6
      months of age (M1-M6). PATIENTS: Patients included 54 full-term (FT; 26 boys) and
      48 preterm (PT; gestational age at birth 27.7-36.6 wk, 22 boys) infants. MAIN
      OUTCOME MEASURES: The occurrence of SGH (present/absent) and acne (5-10, 10-50,
      and >50 papules) was registered and compared with urinary levels of
      dehydroepiandrosterone and its sulphate and testosterone measured by liquid
      chromatography-tandem mass spectrometry. RESULTS: SGH was observed in 89% of FT
      and 96% of PT infants (P = 0.28). Acne (more than five papules) was observed in
      91% of FT infants and in 75% of PT infants (P = 0.06). Both SGH and acne were
      associated with developmental rather than calendar age: SGH was limited to
      postmenstrual age less than 46 wk and acne was not observed less than 37 wk of
      postmenstrual age. Urinary androgen levels showed severalfold differences in
      magnitude between sexes and between the FT and PT groups. After grouping
      according to sex and maturity, the occurrence of SGH and the severity of acne
      were associated with higher urinary dehydroepiandrosterone sulphate and
      testosterone levels in each group. CONCLUSIONS: SGH and acne are common during
      the first months of life and associated with endogenous, physiologically elevated
      levels of androgens originating from the adrenals and gonads. These data suggest
      a novel role for postnatal androgen secretion in infancy.

PMID- 23144472
TI  - Prospective histomorphometric and DXA evaluation of bone remodeling in imatinib
      treated CML patients: evidence for site-specific skeletal effects.
AB  - CONTEXT: Imatinib is a tyrosine kinase inhibitor that has been successfully used
      to treat Philadelphia chromosome-positive chronic myeloid leukemia (CML) and
      Kit(+) gastrointestinal stromal tumors. We have previously shown that imatinib
      therapy is associated with an increase in trabecular bone volume. OBJECTIVE: In
      the present study, we performed a prospective analysis of bone indices in
      imatinib-treated CML patients to determine the mechanism responsible for this
      altered bone remodeling. DESIGN, PATIENTS, AND INTERVENTION: This study assessed
      the effects of high-dose (600 mg/d) imatinib on bone parameters in newly
      diagnosed chronic-phase Philadelphia chromosome-positive CML patients (n = 11)
      enrolled in the TIDEL II study. At baseline and after 6, 12, and 24 months of
      treatment, serum markers of bone remodeling were quantitated, dual-energy x-ray
      absorptiometry analysis of bone mineral density (BMD) was carried out, and a bone
      biopsy was collected for histological and micro-computed tomography analysis.
      RESULTS: Our studies show that the increase in trabecular bone volume and
      trabecular thickness after imatinib treatment was associated with a significant
      decrease in osteoclast numbers, accompanied by a significant decrease in serum
      levels of a marker of osteoclast activity. In contrast, osteoblast numbers were
      not altered by up to 24 months of imatinib treatment. Notably, we also found that
      imatinib caused a site-specific decrease in BMD at the femoral neck. CONCLUSIONS:
      These data suggest that imatinib therapy dysregulates bone remodeling, causing a
      generalized decrease in osteoclast number and activity that is not
      counterbalanced by a decrease in osteoblast activity, leading to increased
      trabecular bone volume. Further long-term investigations are required to
      determine the causes and consequences of the site-specific decrease in BMD at the
      femoral neck.

PMID- 23144471
TI  - Vitamin D status and coronary flow reserve measured by positron emission
      tomography: a co-twin control study.
AB  - CONTEXT: Vitamin D insufficiency is associated with increased cardiovascular
      events in the general population. Additionally, low serum 25-hydroxyvitamin D
      [25(OH)D] is associated with endothelial dysfunction and arterial stiffness.
      However, little is known about the association between serum 25(OH)D level and
      myocardial blood flow. OBJECTIVE: Our objective was to examine the association
      between serum 25(OH)D levels and coronary flow reserve (CFR) measured by (13)N
      positron emission tomography in asymptomatic middle-aged male twins. DESIGN: The
      Emory Twin Study is a cross-sectional study of soldiers from the Vietnam Era
      Registry. SETTING: The study was conducted at the General Clinical Research
      Center, Emory University, Atlanta, GA. PARTICIPANTS: A total of 368 middle-aged
      male twins were enrolled for the study. Serum 25(OH)D levels were measured in all
      subjects and classified as vitamin D insufficiency [25(OH)D <30 ng/ml] or
      sufficiency [25(OH)D >=30 ng/ml]. Positron emission tomography with
      [(13)N]ammonia was used to evaluate myocardial blood flow at rest and after
      adenosine stress. CFR was measured as the ratio of maximum to rest myocardial
      blood flow. MAIN OUTCOME MEASURE: Primary outcome was CFR measurement. RESULTS:
      Mean overall serum 25(OH)D concentration was 37.0 +/- 21.4 ng/ml; 167 twins (45%)
      were vitamin D insufficient. CFR was significantly lower in subjects with vitamin
      D insufficiency compared with subjects with vitamin D sufficiency (2.41 vs. 2.64;
      P = 0.007), even after adjustment for traditional cardiovascular risk factors,
      serum PTH, calcium, and phosphorus levels, and season. An abnormal CFR (CFR <2)
      was more prevalent in subjects with vitamin D insufficiency than with vitamin D
      sufficiency (31 vs. 20%; P = 0.03). In addition, in vitamin D status-discordant
      twin pairs, CFR was significantly lower in the vitamin D-insufficient twin than
      in the vitamin D-sufficient co-twin (2.35 vs. 2.58; P = 0.037). CONCLUSION:
      Vitamin D insufficiency is associated with lower CFR in men. This association may
      help explain some of the increased cardiovascular risk reported in individuals
      with vitamin D insufficiency.

PMID- 23144474
TI  - Call for submissions: advanced dental education.

PMID- 23144473
TI  - Serum antithyroglobulin antibodies interfere with thyroglobulin detection in fine
      needle aspirates of metastatic neck nodes in papillary thyroid carcinoma.
AB  - CONTEXT: It is recommended to measure thyroglobulin (Tg) levels in the needle
      washout fluids from fine-needle aspirations (FNAs) in patients with papillary
      thyroid carcinoma (PTC) who have ultrasonographically suspicious metastatic lymph
      nodes (LNs). However, it is not clear whether serum anti-Tg antibodies (TgAbs)
      interfere with the detection of Tg in needle washout fluids from FNAs (FNA-Tg).
      OBJECTIVE: The objective of the study was to evaluate the influence of serum
      TgAbs on FNA-Tg detection. DESIGN AND SETTINGS: This retrospective observational
      cohort study enrolled 207 patients with conventional PTC in whom FNA-Tg values
      had been measured. All patients initially underwent total thyroidectomy and
      remnant ablation. FNA-Tg levels were measured from ultrasonographically
      suspicious metastatic LNs of 0.5 cm or greater in the longest diameter. RESULTS:
      From 207 patients, 263 LNs were evaluated. Final histopathology was available for
      92 LNs, of which 88 (96%) were malignant. FNA-Tg levels were lower in the LNs
      from serum TgAb-positive patients than in those from TgAb-negative patients (P <
      0.001). In four of 13 metastatic LNs from TgAb-positive patients, the FNA-Tg
      levels were below 10 MUg/liter including one in which both FNA-Tg and serum
      stimulated Tg levels were below 1 MUg/liter and stained positively for Tg in
      pathology. There was also one malignant LN with negative for FNA-Tg, serum
      stimulated Tg, and serum TgAb but that nonetheless stained intensely for Tg.
      However, there were no malignant LNs with both negative cytology and negative FNA
      Tg. A diagnosis based on FNA-Tg had a lower sensitivity and negative predictive
      value in the TgAb-positive group than in the TgAb-negative group. CONCLUSION: FNA
      Tg measurement is highly reliable in the diagnosis of neck metastases in PTC
      patients, even in cases of negative-stimulated Tg or positive TgAb. However, high
      serum TgAb levels could interfere with FNA-Tg measurements and thereby result in
      falsely low FNA-Tg levels.

PMID- 23144475
TI  - The summer institute in clinical dental research methods: still going and growing
      after twenty years.
AB  - The first Summer Institute in Clinical Dental Research Methods, a faculty
      development program at the University of Washington, was offered in the summer of
      1992 for sixteen participants. The primary objective of the program was to give
      clinical faculty members in dentistry an introduction to and an understanding of
      the fundamental principles and methods used in good clinical research. In the
      twentieth offering of the institute in 2011, there were thirty-five participants,
      and over the twenty institutes, there has been a cumulative total of 463
      participants who have come from thirty U.S. states as well as forty-three
      countries outside the United States. The curriculum has expanded from the initial
      offering of biostatistics, clinical epidemiology, behavioral research methods,
      and ethics in clinical research to now include clinical trials, grantsmanship,
      data analysis, an elective in molecular biology, and a team project that provides
      participants with hands-on experience in research proposal development as members
      of an interdisciplinary team. Enrollment has doubled since the first year, yet
      exit evaluations of the program content have remained consistently high (rated as
      very good to excellent). One of the indicators of program quality is that at
      least 50 percent of recent participants indicated that they attended because the
      program was recommended by colleagues who had attended. There seems to be an ever
      increasing pool of dental faculty members who are eager to learn more about
      clinical research methodology through the institute despite the intensive demands
      of full-time participation in a six-week program.

PMID- 23144476
TI  - Factors associated with the satisfaction of millennial generation dental
      residents.
AB  - Data from the 2010 Learners' Perceptions Survey (LPS) administered through the
      Office of Academic Affiliations, Department of Veterans Affairs (VA) were
      analyzed to identify factors associated with dental residents' satisfaction with
      the VA as a clinical training environment. Satisfaction scores were linked to
      clinic workloads, dental procedure complexity levels, staffing patterns, and
      facility infrastructure data to explore conditions that may improve residents'
      satisfaction. Findings supported the construct validity of the LPS survey data
      and underscored the importance of maintaining optimal ratios of attending
      dentists, dental assistants, and administrative staff to residents so that each
      trainee will have opportunities to perform an adequate level of dental workload.
      As programs strive to improve the quality of graduate dental education, findings
      from this study are vital for setting curriculum design guidelines and for
      providing infrastructure support for dental resident education.

PMID- 23144477
TI  - The role of women in dental education: monitoring the pipeline to leadership.
AB  - The purpose of this study was to analyze data collected by the American Dental
      Association and the American Dental Education Association over the past two
      decades relating to changes in the number of women active in dental education and
      dental practice. The concept of a pipeline of women in dentistry was explored by
      analyzing predoctoral, postdoctoral, dental practice, and dental education
      domains for the inclusion of women. Statistical analyses show that there has been
      a consistent and progressive increase in the number of women in all stages of the
      pipeline. Over the past two decades, the number of female students attending and
      graduating from dental school has steadily increased. In 1984-85, 23.7 percent of
      all predoctoral students were women; in 2009-10, 45.1 percent were women.
      Similarly, in 1999, the graduating class was 35.3 percent women; in 2009, it was
      46.1 percent women. In the postdoctoral domain, in 1996, 29.9 percent of all
      residents were women; in 2010, this had increased to 39.0 percent. In dental
      practice, the number of actively licensed women dentists in 1999 was 15.3 percent
      of the workforce; in 2010, this percentage had grown to 24.0 percent. In dental
      education, the number of women clinical faculty members has gradually increased
      from 669 in 1997-98 to 902 in 2007-08. Until 2000, there had been only two women
      deans and very few associate/assistant deans, with only sixteen in 1990. In 2000,
      major changes began with three women deans and seventy-two women
      associate/assistant deans. In 2009-10, there were 111 associate/assistant women
      deans and twelve women deans. These data show a progressive increase in the
      presence of women in all domains of dentistry, especially in leadership positions
      in dental education.

PMID- 23144478
TI  - Cone beam computed tomography in dentistry: what dental educators and learners
      should know.
AB  - Recent advances in cone beam computed tomography (CBCT) in dentistry have
      identified the importance of providing outcomes related to the appropriate use of
      this innovative technology to practitioners, educators, and investigators. To
      assist in determining whether and what types of evidence exist, the authors
      conducted PubMed, Google, and Cochrane Library searches in the spring of 2011
      using the key words "cone beam computed tomography and dentistry." This search
      resulted in over 26,900 entries in more than 700 articles including forty-one
      reviews recently published in national and international journals. This article
      is based on existing publications and studies and will provide readers with an
      overview of the advantages, disadvantages, and indications/contraindications of
      this emerging technology as well as some thoughts on the current educational
      status of CBCT in U.S. dental schools. It is the responsibility of dental
      educators to incorporate the most updated information on this technology into
      their curricula in a timely manner, so that the next generation of oral health
      providers and educators will be competent in utilizing this technology for the
      best interest of patients. To do so, there is a need to conduct studies meeting
      methodological standards to demonstrate the diagnostic efficacy of CBCT in the
      dental field.

PMID- 23144479
TI  - Cone beam computed tomography in dental education: a survey of US, UK, and
      Australian dental schools.
AB  - Cone beam computed tomography (CBCT) is an excellent three-dimensional (3D)
      imaging modality. Traditional dental education has focused on teaching
      conventional (2D) imaging. The aims of this survey-based study were therefore to
      evaluate the incorporation of CBCT teaching in both the predoctoral/undergraduate
      (D.D.S./D.M.D./B.D.S.) and postgraduate/residency specialty training curricula in
      dental schools in the United States, the United Kingdom, and Australia. A nine
      question survey form was electronically mailed to fifty-seven schools in the
      United States, sixteen schools in the United Kingdom, and seven schools in
      Australia. Fifty U.S. dental schools (89 percent), ten U.K. dental schools (62.5
      percent), and one Australian dental school (14 percent) presently have CBCT
      equipment. The majority of responding schools do not include instruction in
      higher level use of this technology for undergraduate/predoctoral students,
      raising questions as to whether these students are adequately trained on
      qualification. Larger numbers of schools reported providing this training to
      residents in specialty programs. A similar trend was noticed in U.S., British,
      and Australian dental education. If general dentists are to be permitted to
      purchase and use CBCT equipment, inclusion of CBCT in dental education is an
      absolute requirement to prepare future dental practitioners to apply 3D imaging
      appropriately for diagnosis and treatment planning.

PMID- 23144480
TI  - Tracking dental patient tobacco use and intervention in the academic clinical
      setting.
AB  - The purpose of this study was to illustrate one method of tracking patients'
      tobacco use and monitoring cessation interventions with electronic dental records
      in an academic dental setting. Records from 465 tobacco users were analyzed to
      assess patients' tobacco use and providers' intervention techniques. The results
      indicate that 75 percent of the patients whose records were analyzed had used
      tobacco for more than ten years and the cold turkey approach was the most common
      cessation method. Ninety-seven percent of the patients whose records were
      analyzed used cigarettes. The most common pharmacotherapy recommended in
      combination with counseling for smoking cessation was the nicotine patch,
      followed by nicotine gum, varenicline (Chantix), the nicotine lozenge, bupropion
      SR (Zyban), and the nicotine oral inhaler. Incorporating tobacco use questions
      into the electronic dental record can ensure that tobacco use and intervention
      techniques are addressed and documented in dental records. Electronic dental
      records provide an opportunity to collect data related to tobacco use and
      intervention techniques for purposes of further evaluation and research.

PMID- 23144481
TI  - Preparing dental students to treat patients with special needs: changes in
      predoctoral education after the revised accreditation standard.
AB  - In its accreditation standards published in 2004, the Commission on Dental
      Accreditation (CODA) adopted a new standard, to be implemented starting in
      January 1, 2006, stating that "Graduates must be competent in assessing the
      treatment needs of patients with special needs." The literature shows that
      academic dental institutions have a history of underpreparing students to deal
      with the increasing population of individuals with special needs. The purpose of
      this study was to survey the then-fifty-four accredited U.S. dental schools to
      determine what if anything had changed since the deadline for implementation of
      the new standard. If dental schools' efforts to meet this standard were found to
      be incomplete or ineffective, the result may be an even greater shortage of
      services for this population and will point to the need for additional efforts in
      this area.

PMID- 23144482
TI  - Periodontal probing calibration in an academic setting.
AB  - The purpose of this study was to locate the common discrepancy sites in a
      periodontal examination by new student dentists in a dental school setting and to
      evaluate student progress after one year of clinical training. Sixty-nine
      patients were enrolled in the initial phase of this study. Periodontal probing
      examinations were performed by both dental students and calibrated faculty
      members. A total of 9,171 sites were probed. Student-faculty agreement was then
      determined for each individual probing site. Frequency of agreement and average
      variance of agreement were calculated for each individual site probed. An
      identical procedure was conducted on thirteen patients by dental students after
      each had received one year of clinical training. A total of 1,991 sites were
      probed. Students new to the clinic had a significantly higher frequency of
      discrepancy in molars of all quadrants, with a trend of highest discrepancy
      shifting from mesial to distal sites when moving posteriorly in the posterior
      region. After one year of experience, there was a significant decline of
      discrepancy in all regions examined. More preclinical emphasis must be placed on
      proper probing technique to ensure accurate probing depths upon entry into the
      clinical setting.

PMID- 23144483
TI  - The role of social media in dental education.
AB  - Social media, also known as Web 2.0, includes a set of web-based technologies in
      which users actively share and create content through open collaboration. The
      current students in dental school are Millennial learners who are comfortable
      using social media, such as Facebook and Twitter, for both socialization and
      learning. This article defines and explores the range of Web 2.0 technologies
      available for use in dental education, addresses their underlying pedagogy, and
      discusses potential problems and barriers to their implementation.

PMID- 23144484
TI  - Using the patient's medication history as a learning tool in clinical
      pharmacology instruction for dental students.
AB  - The purpose of this study was to determine if a pharmacology medical history
      assignment would enable dental students to demonstrate improved knowledge and
      understanding of pharmacology by researching the drugs their patients were taking
      and recording pharmacological information in their patients' health records. The
      study followed a pretest-posttest design and evaluated students' knowledge of ten
      commonly prescribed drugs. Students were given the pretest prior to entry into
      the clinic. Subsequently, for an eight-month period, students completed the
      medication history assignment. Pretest and posttest scores were compared and
      analyzed with one-way ANOVA and Pearson product moment correlation statistics.
      The Pearson product moment correlation showed a positive correlation between the
      drugs per patient and the change in score between the pre- and posttests
      (correlation coefficient=0.254, p=0.016) and between the assignment grade and the
      change in pre- and posttest scores (correlation coefficient=0.198, p<0.001), as
      well as a significant correlation between the number of times a drug was charted
      and the change in score on the pretest-posttest item concerning that drug
      (correlation coefficient=0.798, p=0.006). By documenting patient drug
      information, dental students can improve their pharmacology knowledge base and
      enhance their potential to positively impact patient care and safety.

PMID- 23144485
TI  - Dental students' evaluations of an interactive histology software.
AB  - This study assessed dental students' evaluations of a new Interactive Histology
      Software (IHS) developed by the authors and compared students' assessment of the
      extent to which this new software, as well as other histology teaching methods,
      supported their learning. The IHS is a computer-based tool for histology learning
      that presents high-resolution images of histology basics as well as specific oral
      histologies at different magnifications and with text labels. Survey data were
      collected from 204 first-year dental students at the Universidad Austral de
      Chile. The survey consisted of questions for the respondents to evaluate the
      characteristics of the IHS and the contribution of various teaching methods to
      their histology learning. The response rate was 85 percent. Student evaluations
      were positive for the design, usability, and theoretical-practical integration of
      the IHS, and the students reported they would recommend the method to future
      students. The students continued to value traditional teaching methods for
      histological lab work and did not think this new technology would replace
      traditional methods. With respect to the contribution of each teaching method to
      students' learning, no statistically significant differences (p>0.05) were found
      for an evaluation of IHS, light microscopy, and slide presentations. However,
      these student assessments were significantly more positive than the evaluations
      of other digital or printed materials. Overall, the students evaluated the IHS
      very positively in terms of method quality and contribution to their learning;
      they also evaluated use of light microscopy and teacher slide presentations
      positively.

PMID- 23144486
TI  - The use of independent, interactive media for education in dental morphology.
AB  - Educational researchers have argued for the addition of new technologies to
      enhance or replace traditional dental education modalities to more effectively
      engage and appeal to the new generation of dental students. Two- and three
      dimensional interactive media technology is now available for implementation into
      curricula to teach to a next-generation paradigm. The purpose of this study was
      to analyze the introduction of a unique, online, totally independent learning
      module for dental morphology instruction, completely replacing the traditional
      classroom teaching of the topic, and to determine the relationship between its
      use and parameters depicting success in learning dental morphology. In
      particular, the authors hypothesized that the novice, preclinical dental student
      can learn dental morphology independently and efficiently this way. One-third of
      a 2010-11 first-year class of dental students were given an independent,
      interactive media module for the instruction of dental morphology. The remaining
      members of the class experienced the traditional course with classroom lectures.
      At the end of the module, a written examination and survey were given to both
      groups. The major findings were that the independent, interactive media module
      was just as effective as the traditional classroom method for successful
      dissemination of foundational knowledge in dental morphology; the independent
      study group performed significantly better on the didactic examination; the
      online module positively engaged the students; and students preferred the
      interactive media module but did not regard it as a total replacement for the
      traditional course.

PMID- 23144487
TI  - Croatian dental students' educational experiences and knowledge in regard to
      child abuse and neglect.
AB  - The purpose of this study was to investigate the educational experiences of a
      group of Croatian dental students and to assess their knowledge about child abuse
      and neglect. In the study, 544 respondents (153 male and 391 female) from all six
      years at the University of Zagreb School of Dental Medicine completed
      questionnaires, with a response rate of 74.9 percent. A chi-square test was
      applied to test the differences among students' answers. Values of p<0.05 were
      considered statistically significant. Out of the total number of respondents,
      33.6 percent had encountered the topic of child abuse and neglect during their
      lectures. The results show a lack of knowledge of the signs pointing to physical
      and sexual abuse of children. Students from more senior teaching years showed a
      greater amount of knowledge related to child abuse and neglect in contrast to
      students from more junior teaching years. In conclusion, dental students should
      be better educated and prepared for the important role of helping protect
      children from abuse and neglect.

PMID- 23144488
TI  - Students' perceptions of their education on graduation from a dental school in
      India.
AB  - This study was conducted with the purpose of assessing students' perceived
      learning experience at the time of graduation from a dental school in India. The
      domains appraised were undergraduate curriculum, student motivation and support
      services, institutional infrastructure, administrative services, components of
      teaching-learning programs, confidence level in carrying out specific clinical
      procedures, career choice, and postgraduate specialty preference after
      graduation. The authors surveyed forty-five dental interns at the end of their
      undergraduate course, a 100 percent response rate from the class. The results
      showed that over 95 percent of the graduates were satisfied with the curriculum
      and 60 to 95 percent reported that the various components of the teaching
      learning process were adequate. Only 42 percent of the students were confident
      about setting up a practice; 65 percent wished to take a course on general
      dentistry; and 86 percent wanted to pursue postgraduate study. The principal
      conclusions were that although the program was satisfactory to the majority of
      participants, some areas of concern were identified that need improvement.

PMID- 23144489
TI  - An assessment of the prescribing skills of undergraduate dental students in
      malaysia.
AB  - Most dental schools lack a module on prescription writing in pharmacology. This
      study assessed the prescription writing skills of a group of Malaysian dental
      students at the end of their undergraduate training program. A quantitative study
      of a two-group posttest experiment was designed, and thirty-seven fifth-year
      (final-year) dental students were divided into two groups (A [n=18] and B
      [n=19]). Group A received a didactic lecture on how to write a complete
      prescription, while Group B served as a control group. For prescription writing,
      three standardized dental scenarios with a diagnosis of irreversible pulpitis
      associated with a child and a pregnant woman and periapical pulpitis for an adult
      man were administered. Thus, a total of 111 prescriptions (Group A [n=54] and
      Group B [n=57]) were collected. Twelve elements in each prescription were
      assessed by frequency and a chi-square test. Improvements in eight out of the
      twelve elements were observed in prescriptions written by students in Group A.
      The significantly improved elements were provision of the symbol R(x) (39.8
      percent) (p<0.001), inclusion of the prescriber's signature (75.3 percent)
      (p<0.001), inclusion of the date with the prescriber's signature (54.6 percent)
      (p<0.001), and inclusion of the prescriber's registration (30.5 percent)
      (p<0.001). Overall, Group A gained almost a 50 percent improvement in writing
      complete prescriptions due to the intervening lecture. It appeared a traditional
      lecture led to the more accurate writing of a complete prescription. It was
      suggested that a module on prescription writing be added to the school's
      pharmacology curriculum, so that dental graduates will be competent in
      prescription writing for the sake of their patients' health.

PMID- 23144490
TI  - Dental students' motivations and perceptions of dental professional career in
      India.
AB  - Students' motivations in choosing a career in the health professions are of great
      interest for educators and admission committees, particularly in the field of
      dentistry. This study conducted in four private dental institutions in India was
      designed to investigate dental students' motivations in their choice of dentistry
      as a career and their perceptions regarding dentistry in India. A total of 400
      questionnaires were distributed, and 369 students responded in a combination of
      selected responses to the questions, for a response rate of 92.3 percent. In the
      results, 53.7 percent of the students reported pursuing dentistry because it
      offers stable work (p<0.002); 38.7 percent because the profession is highly paid;
      and 7.6 percent due to the ease in finding a regular job in dental schools or
      hospitals. The survey also found that 44.4 percent of the students pursued
      dentistry because they can determine their own hours of work and 36.6 percent
      said they liked to be their own boss. Among these students, 64.5 percent said
      they were content to be joining dentistry as a professional course, but 35.5
      percent were discontented (p<0.001). Regarding the specialties, 79.1 percent said
      they want to become specialists in the field of dentistry (p<0.001); oral surgery
      was the leading choice followed by orthodontics. Only 11.7 percent reported
      wanting to pursue dentistry for research purposes. Overall, this study found that
      financial and professional factors were the chief criteria for students' pursuing
      dentistry in India; however, the strongest influence in the choice of dentistry
      was the students' parents or family.

PMID- 23144491
TI  - Revising the EU strategy on endocrine disruptors: nearing a decisive moment.

PMID- 23144492
TI  - MSDB: a user-friendly program for reporting distribution and building databases
      of microsatellites from genome sequences.
AB  - Microsatellite Search and Building Database (MSDB) is a new Perl program
      providing a user-friendly interface for identification and building databases of
      microsatellites from complete genome sequences. The general aims of MSDB are to
      use the database to store the information of microsatellites and to facilitate
      the management, classification, and statistics of microsatellites. A user
      friendly interface facilitates the treatment of large datasets. The program is
      powerful in finding various types of pure, compound, and complex microsatellites
      from sequences as well as generating a detailed statistical report in worksheet
      format. MSDB also contains other two subprograms: SWR, which is used to export
      microsatellites from the database to meet user's requirements, and SWP, which is
      used to automatically invoke R to draw a sliding window plot for displaying the
      distribution of density or frequency of identified microsatellites. MSDB is
      freely available under the GNU General Public license for Windows and Linux from
      the following website: http://msdb.biosv.com/.

PMID- 23144493
TI  - The genetic inheritance of the blue-eyed white phenotype in alpacas (Vicugna
      pacos).
AB  - White-spotting patterns in mammals can be caused by mutations in the gene KIT,
      whose protein is necessary for the normal migration and survival of melanocytes
      from the neural crest. The alpaca (Vicugna pacos) blue-eyed white (BEW) phenotype
      is characterized by 2 blue eyes and a solid white coat over the whole body.
      Breeders hypothesize that the BEW phenotype in alpacas is caused by the
      combination of the gene causing gray fleece and a white-spotting gene. We
      performed an association study using KIT flanking and intragenic markers with 40
      unrelated alpacas, of which 17 were BEW. Two microsatellite alleles at KIT
      related markers were significantly associated (P < 0.0001) with the BEW phenotype
      (bew1 and bew2). In a larger cohort of 171 related individuals, we identify an
      abundance of an allele (bew1) in gray animals and the occurrence of bew2
      homozygotes that are solid white with pigmented eyes. Association tests
      accounting for population structure and familial relatedness are consistent with
      a proposed model where these alleles are in linkage disequilibrium with a
      mutation or mutations that contribute to the BEW phenotype and to individual
      differences in fleece color.

PMID- 23144494
TI  - The lupus-prone NZM2410/NZW strain-derived Sle1b sublocus alters the germinal
      center checkpoint in female mice in a B cell-intrinsic manner.
AB  - C57BL/6 (B6) mice carrying the Sle1b sublocus (named B6.Sle1b), which harbors the
      lupus-associated NZM2410/NZW SLAM family genes, produce antinuclear Abs (ANAs).
      However, the role and mechanism(s) involved in the alteration of the germinal
      center (GC) tolerance checkpoint in the development of ANAs in these mice is not
      defined. In this study, we show significantly higher spontaneously formed GCs
      (Spt-GCs) in B6.Sle1b female mice compared with B6 controls. We also found a
      significant increase in CD4(+)CXCR5(hi)PD-1(hi) spontaneously activated
      follicular Th cells in B6.Sle1b female mice. Compared with B6 controls, B6.Sle1b
      female mice had increased numbers of proliferating B cells predominantly located
      in Spt-GCs. The elevated Spt-GCs in B6.Sle1b female mice were strongly associated
      with increased ANA-specific Ab-forming cells and ANA titers. The increased
      numbers of Spt-GCs and spontaneously activated follicular Th cells in B6.Sle1b
      mice were not the result of a generalized defect in B cells expressing Sle1b.
      Consistent with the elevated spontaneous response in B6.Sle1b mice, the
      attenuated GC response characteristic of DNA and p-azophenylarsonate reactive B
      cells from Ig V(H) knock-in mice (termed HKIR) were relieved in adoptively
      transferred recipients in the presence of Sle1b. Finally, by generating mixed
      bone marrow chimeras, we showed that the effect of Sle1b on Spt-GC, follicular Th
      cell, and autoantibody responses in B6.Sle1b mice was B cell autonomous. These
      data indicate that the NZM2410/NZW-derived Sle1b sublocus in conjunction with the
      female sex primarily affects B cells, leading to the alteration of the GC
      tolerance checkpoint and the generation of ANA-specific Ab-forming cells.

PMID- 23144495
TI  - Cutting edge: FAS (CD95) mediates noncanonical IL-1beta and IL-18 maturation via
      caspase-8 in an RIP3-independent manner.
AB  - Fas, a TNF family receptor, is activated by the membrane protein Fas ligand
      expressed on various immune cells. Fas signaling triggers apoptosis and induces
      inflammatory cytokine production. Among the Fas-induced cytokines, the IL-1beta
      family cytokines require proteolysis to gain biological activity. Inflammasomes,
      which respond to pathogens and danger signals, cleave IL-1beta cytokines via
      caspase-1. However, the mechanisms by which Fas regulates IL-1beta activation
      remain unresolved. In this article, we demonstrate that macrophages exposed to
      TLR ligands upregulate Fas, which renders them responsive to receptor engagement
      by Fas ligand. Fas signaling activates caspase-8 in macrophages and dendritic
      cells, leading to the maturation of IL-1beta and IL-18 independently of
      inflammasomes or RIP3. Hence, Fas controls a novel noncanonical IL-1beta
      activation pathway in myeloid cells, which could play an essential role in
      inflammatory processes, tumor surveillance, and control of infectious diseases.

PMID- 23144496
TI  - A combination of local inflammation and central memory T cells potentiates
      immunotherapy in the skin.
AB  - Adoptive T cell therapy uses the specificity of the adaptive immune system to
      target cancer and virally infected cells. Yet the mechanism and means by which to
      enhance T cell function are incompletely described, especially in the skin. In
      this study, we use a murine model of immunotherapy to optimize cell-mediated
      immunity in the skin. We show that in vitro-derived central but not effector
      memory-like T cells bring about rapid regression of skin-expressing cognate Ag as
      a transgene in keratinocytes. Local inflammation induced by the TLR7 receptor
      agonist imiquimod subtly yet reproducibly decreases time to skin graft rejection
      elicited by central but not effector memory T cells in an immunodeficient mouse
      model. Local CCL4, a chemokine liberated by TLR7 agonism, similarly enhances
      central memory T cell function. In this model, IL-2 facilitates the development
      in vivo of effector function from central memory but not effector memory T cells.
      In a model of T cell tolerogenesis, we further show that adoptively transferred
      central but not effector memory T cells can give rise to successful cutaneous
      immunity, which is dependent on a local inflammatory cue in the target tissue at
      the time of adoptive T cell transfer. Thus, adoptive T cell therapy efficacy can
      be enhanced if CD8(+) T cells with a central memory T cell phenotype are
      transferred, and IL-2 is present with contemporaneous local inflammation.

PMID- 23144497
TI  - Leukocyte function antigen-1, kindlin-3, and calcium flux orchestrate neutrophil
      recruitment during inflammation.
AB  - Neutrophil arrest and migration on inflamed endothelium involves a conformational
      shift in CD11a/CD18 (leukocyte function antigen-1; LFA-1) to a high-affinity and
      clustered state that determines the strength and lifetime of bond formation with
      ICAM-1. Cytoskeletal adapter proteins Kindlin-3 and Talin-1 anchor clustered LFA
      1 to the cytoskeleton and facilitate the transition from neutrophil rolling to
      arrest. We recently reported that tensile force acts on LFA-1 bonds inducing
      their colocalization with Orai1, the predominant membrane store operated Ca(2+)
      channel that cooperates with the endoplasmic reticulum to elicit cytosolic flux.
      Because Kindlin-3 was recently reported to initiate LFA-1 clustering in
      lymphocytes, we hypothesized that it cooperates with Orai1 and LFA-1 in signaling
      local Ca(2+) flux necessary for shear-resistant neutrophil arrest. Using
      microfluidic flow channels combined with total internal reflection fluorescence
      microscopy, we applied defined shear stress to low- or high-affinity LFA-1 and
      imaged the spatiotemporal regulation of bond formation with Kindlin-3 recruitment
      and Ca(2+) influx. Orai1 and Kindlin-3 genes were silenced in neutrophil-like HL
      60 cells to assess their respective roles in this process. Kindlin-3 was enriched
      within focal clusters of high-affinity LFA-1, which promoted physical linkage
      with Orai1. This macromolecular complex functioned to amplify inside-out Ca(2+)
      signaling in response to IL-8 stimulation by catalyzing an increased density of
      Talin-1 and consolidating LFA-1 clusters within sites of contact with ICAM-1. In
      this manner, neutrophils use focal adhesions as mechanosensors that convert shear
      stress-mediated tensile force into local bursts of Ca(2+) influx that catalyze
      cytoskeletal engagement and an adhesion-strengthened migratory phenotype.

PMID- 23144498
TI  - Identifying Streetscape Features Significant to Well-Being.
AB  - To determine effective relationships between the built environment and health and
      well-being, a transdisciplinary team of architectural, behavioral and health
      scientists developed a built environment coding system (UMBECS). They examined
      the relationship of resulting streetscape features to health and well-being at
      the block level. The research team conducted studies of the validity of UMBECS
      focusing on children through school conduct and grades, and on elders through a
      longitudinal cognitive functioning study. For children, contrary to popularly
      held views, commercial-residential mix was as effective as a high proportion of
      residential use in predicting children's school outcomes (i.e., better conduct,
      achievement, effort, and grades). For elders, modest but statistically
      significant relationships existed between block-level features, elders'
      neighboring behaviors, and social support, which in turn were significantly
      associated with cognitive and affective functioning. These findings suggest the
      utility of this built environment coding system for examining the relationship of
      built environment features to residents' health and well-being. UMBECS offers a
      useful tool for developing a viable transdisciplinary model of the role of the
      built environment in behavioral and health outcomes.

PMID- 23144499
TI  - The Rich Electrochemistry and Redox Reactions of the Copper Sites in the Cellular
      Prion Protein.
AB  - This paper reviews recent electrochemical studies of the copper complexes of
      prion protein (PrP) and its related peptides, and correlates their redox behavior
      to chemical and biologically relevant reactions. Particular emphasis is placed on
      the difference in redox properties between copper in the octarepeat (OR) and the
      non-OR domains of PrP, as well as differences between the high and low copper
      occupancy states in the OR domain. Several discrepancies in literature concerning
      these differences are discussed and reconciled. The PrP copper complexes, in
      comparison to copper complexes of other amyloidogenic proteins/peptides, display
      a more diverse and richer redox chemistry. The specific protocols and caveats
      that need to be considered in studying the electrochemistry and redox reactions
      of copper complexes of PrP, PrP-derived peptides, and other related amyloidogenic
      proteins are summarized.

PMID- 23144500
TI  - An Implicit Elastic Theory for Lung Parenchyma.
AB  - The airways and parenchyma of lung experience large deformations during normal
      respiration. Spatially accurate predictions of airflow patterns and aerosol
      transport therefore require respiration to be modeled as a fluid-structure
      interaction problem. Such computational models in turn require constitutive
      models for the parencyhma that are both accurate and efficient. Herein, an
      implicit theory of elasticity is derived from thermodynamics to meet this need,
      leading to a generic template for strain-energy that is shown to be an exact
      analogue for the well-known Fung model that is the root of modern constitutive
      theory of tissues. To support this theory, we also propose a novel definition of
      Lagrangian strain rate. Unlike the classic definition of Lagrangian strain rate,
      this new definition is separable into volumetric and deviatoric terms, a
      separation that is both mathematically and physically justified. Within this
      framework, a novel material model capable of describing the elastic contribution
      of the nonlinear response of parenchyma is constructed and characterized against
      published data.

PMID- 23144501
TI  - Smiling and sad wrinkles: Age-related changes in the face and the perception of
      emotions and intentions.
AB  - There is a common belief that wrinkles in the aging face reflect frequently
      experienced emotions and hence resemble these affective displays. This implies
      that the wrinkles and folds in elderly faces interfere with the perception of
      other emotions currently experienced by the elderly as well as with the
      inferences perceivers draw from these expressions. Whereas there is ample
      research on the impact of aging on emotion recognition, almost no research has
      focused on how emotions expressed by the elderly are perceived by others. The
      present research addresses this latter question. Young participants rated the
      emotion expressions and behavioral intentions of old and young faces displaying
      identical expressions. The findings suggest that emotions shown on older faces
      have reduced signal clarity and may consequently have less impact on inferences
      regarding behavioral intentions. Both effects can be expected to have negative
      consequences for rapport achieved in everyday interactions involving the elderly.

PMID- 23144502
TI  - Developmental Patterns in Marital Satisfaction: Another Look at Covenant
      Marriage.
AB  - This study investigated differences in the trajectory of marital satisfaction in
      the first seven years between couples in covenant vs. standard marriages. Data on
      707 Louisiana marriages from the Marriage Matters Panel Survey of Newlywed
      Couples, 1998 - 2004, were analyzed using multivariate longitudinal growth
      modeling. Restricting the sample to couples who remained married over the
      duration of the study, a marginal benefit of covenant status was found for
      husbands. This effect was largely accounted for by covenant husbands' more
      extensive exposure to premarital counseling. The linear decline in marital
      satisfaction over time that obtained for both husbands and wives was not,
      however, any different for covenants vs. standards. Couples characterized by more
      traditional attitudes toward gender roles were significantly less satisfied than
      others. High premarital risk factors, initial uncertainty about marrying the
      spouse, and the presence of preschool children in the household were all
      corrosive of marital satisfaction at any given time.

PMID- 23144503
TI  - All stimuli are equal, but some are more equal than others: measuring relational
      preferences within an equivalence class.
AB  - Two experiments used post-class formation within-class relational assessment test
      performances to evaluate whether participants demonstrated preference for certain
      members of an equivalence class based on the type of relation that existed
      between class members. In Experiment 1, two 5-node 7-member equivalence classes,
      consisting entirely of nonsense syllables, were established using the
      simultaneous protocol. Only 1 of the 6 participants in Experiment 1 formed
      classes. After class formation, the effects of the different relations between
      stimuli were evaluated using within-class relational assessment tests, and the 1
      participant showed an absolute preference for transitive over equivalence
      relations, and for baseline over symmetrical relations. Experiment 2 was
      identical to Experiment 1, except that one of the nonsense syllable stimuli in
      each class was replaced by a pictorial stimulus. Under these conditions, classes
      were formed by 5 of 13 participants. During the relational assessment tests, the
      5 participants who formed classes demonstrated almost exclusive preferences for
      transitive relations over equivalence relations and for trained baseline
      relations over symmetrical relations. Thus, this research demonstrates that the
      members of equivalence classes are differentially related to each other based on
      relational type.

PMID- 23144504
TI  - Assessing the role of effort reduction in the reinforcing efficacy of timeout
      from avoidance.
AB  - Rats responded on concurrent schedules of shock-postponement or deletion
      (avoidance) and timeout from avoidance. In Experiment 1, 3 rats' responses on one
      lever postponed shocks for 20 s and responses on a second lever produced a 1-min
      timeout according to a variable-interval 45-s schedule. Across conditions, a
      warning signal (white noise) was presented 19.5 s, 16 s, 12 s, 8 s, or 4 s before
      an impending shock. Raising the duration of the warning signal increased both
      avoidance and timeout response rates. Timeout responding, although positively
      correlated with avoidance responding, was not correlated with the prevailing
      shock rate. In Experiment 2, 3 rats' responses on one lever deleted scheduled
      shocks according to a variable-cycle 30-s schedule and responses on a second
      lever produced a 2-min timeout as described above. After this baseline condition,
      the avoidance lever was removed and noncontingent shocks were delivered at
      intervals yoked to the receipt of shocks in the baseline sessions. Timeout
      responding decreased when the avoidance lever was removed, even though the shock
      frequency reduction afforded by the timeout remained constant. These results
      suggest that a key factor in the reinforcing efficacy of timeout is suspension of
      the requirement to work to avoid shock, rather than the reduction in shock
      frequency associated with timeout.

PMID- 23144505
TI  - Reinforcer magnitude attenuates: apomorphine's effects on operant pecking.
AB  - When given to pigeons, the direct-acting dopamine agonist apomorphine elicits
      pecking. The response has been likened to foraging pecking because it bears
      remarkable similarity to foraging behavior, and it is enhanced by food
      deprivation. On the other hand, other data suggest the response is not related to
      foraging behavior and may even interfere with food ingestion. Although elicited
      pecking interferes with food capture, it may selectively alter procurement phases
      of feeding, which can be isolated in operant preparations. To explore the
      relation between operant and elicited pecking, we provided pigeons the
      opportunity to earn different reinforcer magnitudes during experimental sessions.
      During signaled components, each of 4 pigeons could earn 2-, 4-, or 8-s access to
      grain for a single peck made at the end of a 5-min interval. In general,
      responding increased as a function of reinforcer magnitude. Apomorphine increased
      pecking for 2 pigeons and decreased pecking for the other 2. In both cases,
      apomorphine was more potent under the component providing the smallest reinforcer
      magnitude. Analysis of the pattern of pecking across the interval indicated that
      behavior lost its temporal organization as dose increased. Because apomorphine
      induced pecking varied inversely with reinforcer magnitude, we conclude that
      elicited pecks are not functionally related to food procurement. The data are
      consistent with the literature on behavioral resistance to change and suggest
      that the effects of apomorphine may be modulated by prevailing stimulus
      reinforcer relationships.

PMID- 23144506
TI  - A replication and extension of the antisymmetry effect in pigeons.
AB  - Pigeons trained on successive AB symbolic matching show emergent BA antisymmetry
      if they are also trained on successive AA oddity and BB identity (Urcuioli, 2008,
      Experiment 4). In other words, when tested on BA probe trials following training,
      they respond more to the comparisons on the reverse of the nonreinforced AB
      baseline trials than on the reverse of the reinforced AB baseline trials (the
      opposite of an associative symmetry pattern). The present experiment replicated
      this finding. In addition, it showed that antisymmetry also emerged after
      baseline training on successive AB symbolic matching, AA identity, and BB oddity,
      consistent with the prediction from Urcuioli's (2008) theory of pigeons' stimulus
      class formation. Together, these results provide further empirical support for
      that theory including the proposition that the functional stimuli in pigeons'
      successive matching consist of the nominal stimuli plus their ordinal positions
      within a trial.

PMID- 23144507
TI  - Effects of a signaled delay to reinforcement in the previous and upcoming ratios
      on between-ratio pausing in fixed-ratio schedules.
AB  - Domestic hens responded under multiple fixed-ratio fixed-ratio schedules with
      equal fixed ratios. One component provided immediate reinforcement and the other
      provided reinforcement after a delay, signaled by the offset of the key light.
      The components were presented quasirandomly so that all four possible transitions
      occurred in each session. The delay was varied over 0, 4, 8, 16, and 32 s with
      fixed-ratio 5 schedules, and over 0, 8 and 32 s with fixed-ratio 1, 15 and 40
      schedules. Main effects of fixed-ratio value and delay duration were detected on
      between-ratio pauses. Pauses were longer when the multiple-schedule stimulus
      correlated with a delayed-reinforcer component was presented, with the longest
      pauses occurring at the transition from a component with an immediate reinforcer
      to one with a delayed reinforcer. Pause durations were shortest during immediate
      components. Overall, both the presence or absence of a delay in the upcoming
      component, and the presence or absence of a delay in the preceding component
      affected pause length, but the upcoming delay had the larger effect. Thus changes
      in delay had similar effects to past reports of the effects of changes in
      response force, response requirement, and reinforcer magnitude in multiple fixed
      ratio fixed-ratio schedules.

PMID- 23144508
TI  - Suppressive and facilitative effects of shock intensity and interresponse times
      followed by shock.
AB  - Although response-dependent shock often suppresses responding, response
      facilitation can occur. In two experiments, we examined the suppressive and
      facilitative effects of shock by manipulating shock intensity and the
      interresponse times that produced shock. Rats' lever presses were reinforced on a
      variable-interval 40-s schedule of food presentation. Shock followed either long
      or short interresponse times. Shock intensity was raised from 0.05 mA to 0.4 mA
      or 0.8 mA. Overall, shock contingent on long interresponse times punished long
      interresponse times and increased response rates. Shock contingent on short
      interresponse times punished short interresponse times and decreased response
      rates. In Experiment 1, raising the range of interresponse times that produced
      shock enhanced these effects. In Experiment 2, the effects of shock intensity
      depended on the interresponse times that produced shock. When long interresponse
      times produced shock, low intensities increased response rates. High intensities
      decreased response rates. When short interresponse times produced shock, high
      shock intensities punished short interresponse times and decreased response rates
      more than low intensities. The results may explain why punishment procedures
      occasionally facilitate responding and establish parameters for future studies of
      punishment.

PMID- 23144509
TI  - Discrimination of variable schedules is controlled by interresponse times
      proximal to reinforcement.
AB  - In Experiment 1, food-deprived rats responded to one of two schedules that were,
      with equal probability, associated with a sample lever. One schedule was always
      variable ratio, while the other schedule, depending on the trial within a
      session, was: (a) a variable-interval schedule; (b) a tandem variable-interval,
      differential-reinforcement-of-low-rate schedule; or (c) a tandem variable
      interval, differential-reinforcement-of-high-rate schedule. Completion of a
      sample-lever schedule, which took approximately the same time regardless of
      schedule, presented two comparison levers, one associated with each sample-lever
      schedule. Pressing the comparison lever associated with the schedule just
      presented produced food, while pressing the other produced a blackout.
      Conditional-discrimination accuracy was related to the size of the difference in
      reinforced interresponse times and those that preceded it (predecessor
      interresponse times) between the variable-ratio and other comparison schedules.
      In Experiment 2, control by predecessor interresponse times was accentuated by
      requiring rats to discriminate between a variable-ratio schedule and a tandem
      schedule that required emission of a sequence of a long, then a short
      interresponse time in the tandem's terminal schedule. These discrimination data
      are compatible with the copyist model from Tanno and Silberberg (2012) in which
      response rates are determined by the succession of interresponse times between
      reinforcers weighted so that each interresponse time's role in rate determination
      diminishes exponentially as a function of its distance from reinforcement.

PMID- 23144510
TI  - Comparing pleasure and pain: the fundamental mathematical equivalence of reward
      gain and shock reduction under variable interval schedules.
AB  - The relationship between positive and negative reinforcement and the symmetry of
      Thorndike's law of effect are unresolved issues in operant psychology. Here we
      show that, for a given pattern of responding on variable interval (VI) schedules
      with the same programmed rate of food rewards (positive reinforcement VI) or
      electric shocks (negative reinforcement VI), there is a fundamental mathematical
      equivalence between reward gain and shock reduction. We also provide the first
      normative account of how animals should respond on a negative VI schedule,
      showing that it is better to space responses evenly than to respond with a
      variable interresponse time (IRT). Published data from rats, however, indicate
      that these animals respond irregularly, often with a burst of activity
      immediately following a shock. While this is irrational in the experimental
      setting, it may represent an appropriate response to the heterogeneity of stimuli
      commonly encountered in natural environments. We discuss the broader implications
      of our analysis for understanding how animals evaluate appetitive and aversive
      stimuli.

PMID- 23144511
TI  - A Third Moment Adjusted Test Statistic for Small Sample Factor Analysis.
AB  - Goodness of fit testing in factor analysis is based on the assumption that the
      test statistic is asymptotically chi-square; but this property may not hold in
      small samples even when the factors and errors are normally distributed in the
      population. Robust methods such as Browne's asymptotically distribution-free
      method and Satorra Bentler's mean scaling statistic were developed under the
      presumption of non-normality in the factors and errors. This paper finds new
      application to the case where factors and errors are normally distributed in the
      population but the skewness of the obtained test statistic is still high due to
      sampling error in the observed indicators. An extension of Satorra Bentler's
      statistic is proposed that not only scales the mean but also adjusts the degrees
      of freedom based on the skewness of the obtained test statistic in order to
      improve its robustness under small samples. A simple simulation study shows that
      this third moment adjusted statistic asymptotically performs on par with
      previously proposed methods, and at a very small sample size offers superior Type
      I error rates under a properly specified model. Data from Mardia, Kent and
      Bibby's study of students tested for their ability in five content areas that
      were either open or closed book were used to illustrate the real-world
      performance of this statistic.

PMID- 23144512
TI  - Reversible alpha-helix formation controlled by a hydrogen bond surrogate.
AB  - Strategically placed covalent linkages have been shown to stabilize helical
      conformations in short peptide sequences. Here we report the synthesis of a
      stabilized alpha-helix that utilizes an internal disulfide linkage. Structural
      analysis indicates that the dynamic nature of the disulfide bridge allows for the
      reversible formation of an alpha-helix through oxidation and reduction reactions.

PMID- 23144513
TI  - Evaluation of poly(amidoamine) dendrimers as potential carriers of iminodiacetic
      derivatives using solubility studies and 2D-NOESY NMR spectroscopy.
AB  - The interactions between dendrimers and different types of drugs are nowadays one
      of the most actively investigated areas of the pharmaceutical sciences. The
      interactions between dendrimers and drugs can be divided into: internal
      encapsulation, external electrostatic interaction, and covalent conjugation. In
      the present study, we investigated the potential of poly(amidoamine) (PAMAM)
      dendrimers for solubility of four iminodiacetic acid derivatives. We reported
      that PAMAM dendrimers contribute to significant solubility enhancement of
      iminodiacetic acid analogues. The nature of the dendrimer-drug complexes was
      investigated by (1)H NMR and 2D-NOESY spectroscopy. The (1)H NMR analysis proved
      that the water-soluble supramolecular structure of the complex was formed on the
      basis of ionic interactions between terminal amine groups of dendrimers and
      carboxyl groups of drug molecules, as well as internal encapsulation. The 2D
      NOESY analysis revealed interactions between the primary amine groups of PAMAM
      dendrimers and the analogues of iminodiacetic acid. The results of solubility
      studies together with (1)H NMR and 2D-NOESY experiments suggest that the
      interactions between PAMAM dendrimers of generation 1-4 and derivatives of
      iminodiacetic acid are based on electrostatic interactions and internal
      encapsulation.Electronic supplementary material The online version of this
      article (doi:10.1007/s10867-012-9277-5) contains supplementary material, which is
      available to authorized users.

PMID- 23144514
TI  - Empathic concern: Distinguishing between tenderness and sympathy.
AB  - The present research proposes that empathic concern, as assessed by six items of
      the ERQ, consists of two separate emotions, i.e., tenderness and sympathy. To
      test this assumption, nine studies were conducted among, in total, 1,273
      participants. In these studies participants were presented with a hypothetical
      scenario of someone in need, after which empathic concern was assessed. Factor
      analyses showed that, indeed, the ERQ items that assess empathic concern can be
      split up in two factors, that is, one reflecting sympathy and one reflecting
      tenderness. In addition, in line with previous studies, our research showed that,
      in response to a need-situation that reflects current needs, individuals scored
      higher on the ERQ factor reflecting sympathy than on the ERQ factor reflecting
      tenderness. Findings are discussed in terms of the practical and theoretical
      implications of distinguishing between sympathy and tenderness.

PMID- 23144515
TI  - General, Specific and Unique Cognitive Factors Involved in Anxiety and Depressive
      Disorders.
AB  - Comorbidity among anxiety and depressive disorders is the rule rather than the
      exception. The Integrative Hierarchical Model proposes that each of these
      disorders contains general (common to all), specific (common to some) and unique
      components. However, research into this model is limited and hampered by small
      (clinical) sample sizes. The aim of the present study is to investigate the
      incremental validity of the cognitive constructs Anxiety Sensitivity,
      Pathological Worry and Cognitive Reactivity to sad mood over and above the
      personality traits neuroticism and extraversion. Symptomatic (N = 1,111) and
      remitted (N = 834) patients were selected from the 2,981 participants of the
      Netherlands Study of Depression and Anxiety (NESDA). Results revealed both
      specific and unique cognitive components of anxiety and depression. Across
      symptomatic and remitted groups, Anxiety Sensitivity was specific to social
      anxiety disorder and panic disorder, Aggression Reactivity was a unique component
      of dysthymia, and Rumination on Sadness was unique to major depressive disorder.
      We conclude that cognitive constructs have additional value in understanding
      anxiety and depressive disorders. Moreover, they prove to be more than mere
      epiphenomena of current disorders.

PMID- 23144516
TI  - How Disorder-Specific are Depressive Attributions? A Comparison of Individuals
      with Depression, Post-Traumatic Stress Disorder and Healthy Controls.
AB  - Depressed individuals tend to assign internal, stable, and global causes to
      negative events. The present study investigated the specificity of this effect to
      depression and compared depressive attributional styles of individuals with major
      depression (MD), post-traumatic stress disorder (PTSD), and healthy controls. We
      indexed attributional style using the depressive attributions questionnaire in
      164 participants. Additionally, we assessed appraisals characteristic of PTSD
      using the post-traumatic cognitions inventory (PTCI), depressive rumination,
      trauma history, and depression and PTSD symptom severity. Individuals with MD
      endorsed a depressive attributional style to a greater extent than both
      individuals with PTSD, who were not depressed, and healthy controls. Depressive
      attributional style was associated with the severity of depressive and PTSD
      symptoms, number and distress of traumatic experiences, frequency of rumination,
      and post-traumatic cognitions. Depressive attributions and PTCI appraisals
      independently predicted MD and PTSD symptom severity. They may thus be useful in
      predicting MD and PTSD, and should be targeted in psychological treatments of
      these conditions.

PMID- 23144517
TI  - Anticipation of Social Interaction Changes Implicit Approach-Avoidance Behavior
      of Socially Anxious Individuals.
AB  - Earlier research has revealed implicit avoidance of social stimuli in social
      anxiety (SA). This study investigated such reactions in anticipation of social
      interaction. High (n = 24) and low (n = 22) SA females were assessed in
      anticipation of a getting-acquainted conversation (anticipation) and in a no
      conversation-expected (neutral) condition. The Face-Turn Approach Avoidance Task
      was used in which participants responded to profiles of human faces or control
      stimuli by either pulling (approach) or pushing (avoidance) a joystick. Upon
      pulling, the stimuli turned toward the participant, while they turned away upon
      pushing. The results demonstrated the expected decreased approach response to
      faces in the neutral condition for the high SAs compared to the low SAs group.
      Unexpectedly, in the anticipation condition the high SAs showed increased
      approach tendencies to faces whereas, the low SAs demonstrated a decreased
      approach response. The implicit social approach response of the high SAs in the
      anticipation condition is discussed.

PMID- 23144518
TI  - Cognitive Distortions and Self-Regulatory Personality Traits Associated with
      Proactive and Reactive Aggression in Early Adolescence.
AB  - This study investigated mechanisms behind proactive and reactive aggression, by
      examining whether four types of self-serving cognitive distortions and the
      personality traits agreeableness and conscientiousness differently predicted
      proactive and reactive aggression. Self-report questionnaires and a peer
      nominations method were administered to 173 sixth grade children (age 10-13) of
      regular elementary schools in the Netherlands. Negative binomial regression
      analyses showed that proactive aggression was predicted by self-centered and
      disagreeable tendencies, whereas reactive aggression was predicted by the
      misattribution of blame to others and the self-regulatory aspects of
      agreeableness and conscientiousness. Findings emphasize the need to differentiate
      proactive and reactive aggression in order to accurately predict, prevent and
      treat aggressive behaviors in childhood.

PMID- 23144519
TI  - Relationship-Relevant and Family-Friendly eHealth: Innovations in Interactive
      Health Communication Systems.
AB  - As the reach of the Internet grows, eHealth is fast becoming a major adjunct to
      traditional delivery of health information and support worldwide. Existing
      Interactive health communication systems, however, typically target individual
      users, focus on individual rather than on relational health, and neglect the
      relational and familial context of individual health issues. Reviewing
      developments primarily in the United States, this article applies a "marriage and
      family lens" to examine web-based technologies for health and well-being and
      suggests innovations to make eHealth both relationship relevant and family
      friendly. Although recent innovations offer great promise for supporting the
      relational "fabric" of family life, specific cautions and the need for research
      on effectiveness are underscored.

PMID- 23144520
TI  - Nonparametric Regression With Missing Outcomes Using Weighted Kernel Estimating
      Equations.
AB  - We consider nonparametric regression of a scalar outcome on a covariate when the
      outcome is missing at random (MAR) given the covariate and other observed
      auxiliary variables. We propose a class of augmented inverse probability weighted
      (AIPW) kernel estimating equations for nonparametric regression under MAR. We
      show that AIPW kernel estimators are consistent when the probability that the
      outcome is observed, that is, the selection probability, is either known by
      design or estimated under a correctly specified model. In addition, we show that
      a specific AIPW kernel estimator in our class that employs the fitted values from
      a model for the conditional mean of the outcome given covariates and auxiliaries
      is double-robust, that is, it remains consistent if this model is correctly
      specified even if the selection probabilities are modeled or specified
      incorrectly. Furthermore, when both models happen to be right, this double-robust
      estimator attains the smallest possible asymptotic variance of all AIPW kernel
      estimators and maximally extracts the information in the auxiliary variables. We
      also describe a simple correction to the AIPW kernel estimating equations that
      while preserving double-robustness it ensures efficiency improvement over
      nonaugmented IPW estimation when the selection model is correctly specified
      regardless of the validity of the second model used in the augmentation term. We
      perform simulations to evaluate the finite sample performance of the proposed
      estimators, and apply the methods to the analysis of the AIDS Costs and Services
      Utilization Survey data. Technical proofs are available online.

PMID- 23144521
TI  - Living Arrangements and the Well-being of Single Mothers in Japan.
AB  - The goal of this paper is to evaluate the extent to which the well-being of
      single mothers in Japan is related to coresidence with other adults. Using data
      from a representative survey of households headed by single mothers, we examine
      two measures of subjective well-being: perceived economic circumstances and self
      rated health. One-fourth of the single mothers surveyed were coresiding with
      another adult(s) and it is clear that these women fare significantly better than
      their non-coresiding counterparts on both measures of well-being. Net of several
      theoretically relevant sociodemographic, family, and employment characteristics,
      single mothers living with others were significantly less likely to report
      somewhat difficult/difficult economic circumstances or fair/poor health. Efforts
      to account for potential endogeneity between well-being and living arrangements
      suggested that self-rated health, but not subjective economic well-being, is
      related to selection into coresidence. Single mothers in fair/poor health appear
      more likely to coreside with others and, accounting for this selection,
      intergenerational coresidence appears to be very beneficial for self-rated
      health. We discuss the implications of these findings for processes of
      stratification in Japan in light of the limited public income support available
      to single mothers.

PMID- 23144522
TI  - Quality Tetrahedral Mesh Smoothing via Boundary-Optimized Delaunay Triangulation.
AB  - Despite its great success in improving the quality of a tetrahedral mesh, the
      original optimal Delaunay triangulation (ODT) is designed to move only inner
      vertices and thus cannot handle input meshes containing "bad" triangles on
      boundaries. In the current work, we present an integrated approach called
      boundary-optimized Delaunay triangulation (B-ODT) to smooth (improve) a
      tetrahedral mesh. In our method, both inner and boundary vertices are
      repositioned by analytically minimizing the  error between a paraboloid function
      and its piecewise linear interpolation over the neighborhood of each vertex. In
      addition to the guaranteed volume-preserving property, the proposed algorithm can
      be readily adapted to preserve sharp features in the original mesh. A number of
      experiments are included to demonstrate the performance of our method.

PMID- 23144523
TI  - Determinants of Pair-Living in Red-Tailed Sportive Lemurs (Lepilemur
      ruficaudatus).
AB  - Pair-living and a monogamous mating strategy are rare and theoretically
      unexpected among mammals. Nevertheless, about 10% of primate species exhibit such
      a social system, which is difficult to explain in the absence of paternal care.
      In this study, we investigated the two major hypotheses proposed to explain the
      evolution of monogamy in mammals, the female defence hypothesis (FDH) and the
      resource defence hypothesis (RDH), in red-tailed sportive lemurs (Lepilemur
      ruficaudatus), a nocturnal primate from Madagascar. We analysed behavioural data
      from eight male-female pairs collected during a 24-mo field study to illuminate
      the determinants of pair-living in this species. Male and female L. ruficaudatus
      were found to live in dispersed pairs, which are characterised by low cohesion
      and low encounter rates within a common home range. Social interactions between
      pair partners were mainly agonistic and characterised by a complete absence of
      affiliative interactions - body contact was only observed during mating. During
      the short annual mating season, males exhibited elevated levels of aggression
      towards mates, as well as extensive mate guarding and increased locomotor
      activity. In addition, males were exclusively responsible for the maintenance of
      proximity between pair partners during this period, and they defended their
      territories against neighbouring males but not against females. Together, these
      results point towards the importance of female defence in explaining pair-living
      in L. ruficaudatus. We discuss the spatial and temporal distribution of receptive
      females in relation to the female defence strategies of males and suggest
      possible costs that prevent male red-tailed sportive lemurs from defending more
      than one female.

PMID- 23144524
TI  - Lifestyle Activities in Sociodemographically at-risk Urban, Older Adults Prior to
      Participation in the Baltimore Experience Corps((r)) Trial.
AB  - Experience Corps((r)) places teams of trained volunteers in elementary school
      classrooms to promote academic achievement in children, and serve as a health
      promotion intervention for older adults. Prior to randomization, individuals
      reported participation in several activities of varying cognitive, physical, and
      social demands. Maintaining an active lifestyle, particularly in intellectually
      demanding activities, was associated with physical, mental, and cognitive health
      in adulthood. Establishing how individuals allocated their time before
      randomization to this program provides insight to prevalent health behaviors for
      at-risk older adults, and can provide the basis for examining intervention
      related changes in lifestyle as a result of volunteer participation.

PMID- 23144525
TI  - Spouse Control and Type 2 Diabetes Management: Moderating Effects of Dyadic
      Expectations for Spouse Involvement.
AB  - For married patients, chronic illness management often includes involvement of
      their spouses. We examined expectations regarding spouse involvement in the
      health of a partner with type 2 diabetes (N = 139 couples) from the perspectives
      of the patient and spouse. Partners' dyadic expectations and spouses' gender were
      posited to moderate spouses' diet-related control and patients' diet adherence.
      Among male patients, when both partners shared an expectation for spouse
      involvement greater diet-related spouse control was associated with better diet
      adherence of patients. In contrast, when expectations for spouse involvement were
      not shared, greater spouse control by wives was associated with poorer diet
      adherence. Dyadic expectations for spouse involvement did not moderate the
      association between spouse control and diet adherence among female patients.
      Findings suggest that shared expectations for spouse involvement can facilitate
      spouses' attempts to improve patients' dietary adherence, especially among male
      patients and their wives.

PMID- 23144526
TI  - Divining Testimony? The Impact of Interviewing Props on Children's Reports of
      Touching.
AB  - There is a long-held assumption that objects help bridge the gap between what
      children know and what they can (or are willing to) explain. In this review, we
      present research on the extent to which two types of objects used as props in
      investigative interviews of children, anatomical dolls and body (human figure)
      diagrams, actually help children report accurate information about
      autobiographical events. We explain why available research does not instill
      confidence that props are the best solution to interviewing challenges, and we
      consider practitioners' and policy-makers responses to this evidence. Finally, we
      discuss the types of developmental research that are necessary to advance the
      field of evidence-based interviewing of children.

PMID- 23144528
TI  - A comparative morphology of the male genitalia of Aphididae (Insecta, Hemiptera):
      part 2.
AB  - The present study provides new data related to the morphology of the male
      genitalia of Aphididae. The structure of the male genitalia of 39 species from 23
      genera of Aphididae was studied using light and scanning electron microscopy. In
      the species studied, the genitalia of males consist of a phallus composed of the
      sclerotized basal part with its articulation and a membranous apical part-an
      aedeagus as well as parameres. This state probably represents the hypothetical
      plesiomorphic condition of the external male genitalia of aphids. According to
      the results of the present study, the male genitalia vary among subfamilies (the
      most varied in Lachninae). Both the phallus and parameres show great variability
      in their form and the number of setae and may provide characters of taxonomic and
      diagnostic importance. The shape, size, and modification of parameres are
      considered in conjunction with the phylogenetic relationships among the studied
      taxa. Compared with Lachninae, Greenideinae, Aiceoninae, the external genitalia
      of Aphidinae are less specialized, having many features in common with those of
      drepanosiphine aphids and differing little from the hypothetical condition. In
      dwarfish males of Anoeciinae, Thelaxinae, Hormaphidinae, and Eriosomatinae, the
      miniaturization of the body size affects on the modification of genitalia, mostly
      parameres. However, the homology of non-modified and modified structures of
      parameres is not clear.

PMID- 23144527
TI  - Clustering of High Throughput Gene Expression Data.
AB  - High throughput biological data need to be processed, analyzed, and interpreted
      to address problems in life sciences. Bioinformatics, computational biology, and
      systems biology deal with biological problems using computational methods.
      Clustering is one of the methods used to gain insight into biological processes,
      particularly at the genomics level. Clearly, clustering can be used in many areas
      of biological data analysis. However, this paper presents a review of the current
      clustering algorithms designed especially for analyzing gene expression data. It
      is also intended to introduce one of the main problems in bioinformatics -
      clustering gene expression data - to the operations research community.

PMID- 23144529
TI  - Associations of Social Support and 8-Year Follow-Up Depressive Symptoms:
      Differences in African American and White Caregivers.
AB  - The present study used data from the Alzheimer's Study of Emotions in Caregivers
      (ASEC) to evaluate perceptions of social support assessed at baseline, as well as
      changes in social support assessed at a follow-up eight-years later, as
      predictors of symptoms of change in depression, with a focus on race as a
      potential moderator of these relationships. Specifically, multiple regression
      analyses adjusted for age, sex, income, education, race, living arrangement of
      care recipient at baseline, death of care recipient, the cultural justification
      for caregiving scale (CJCS), and baseline depressive symptoms were conducted to
      assess baseline social support ratings, as well as the change in social support
      over time as a predictor of depression at follow-up-with a focus on moderation by
      race. Baseline social support (F(1,77) = 7.60, p=.008) was associated with fewer
      depressive symptoms at follow-up for all participants. The change in social
      support over time was also related to depressive symptoms, with effects moderated
      by race (F(1,77) = 7.97, p = .007), such that when support decreased over time
      depressive symptoms at follow-up were higher for Whites, as compared with African
      Americans, whereas, when social support increased over time depressive symptoms
      tended to be similar for both groups. These findings indicate that research
      designed to plan interventions in caregivers must not ignore potential racial
      differences with regard to the effects of caregiving on mental health.

PMID- 23144530
TI  - The Experience of Sexual Risk Communication in African American Families Living
      With HIV.
AB  - Mother-daughter communication plays an influential role in adolescent
      development. The impact of maternal HIV infection on family communication is not
      clear. This study explores how living with HIV impacts sexual risk communication
      between mothers and daughters and whether maternal HIV status influences
      adolescent choices about engagement in HIV risk behaviors. Data were collected
      from 12 African American women and 10 of their adolescent daughters through focus
      groups. Both mothers and daughters shared information about issues that promoted
      and inhibited communication and engagement in risk behaviors. Findings show that
      HIV status served as a mechanism for behavioral change related to communication
      and risk engagement behaviors. Therefore, HIV-infected mothers should be
      supported in communicating values and expectations to their daughters.

PMID- 23144531
TI  - Abused Mothers' Safety Concerns and Court Mediators' Custody Recommendations.
AB  - This study adds to research on family court's response to custody in the context
      of intimate partner abuse (IPA). Mediation is often used to assist family court
      with custody negotiation; however, debate exists in the field regarding its use
      when IPA exists. The following study examines experiences with court mediation
      among a sample of victimized mothers who divorced abusive husbands. Mixed-method
      data were collected from 19 women. Findings demonstrate that abuse is rarely
      considered in custody recommendations, as most court mediators prefer joint
      custody. Implications for the ongoing debate, as well as future directions for
      research, are discussed.

PMID- 23144532
TI  - Investigation of In Vitro Bone Cell Adhesion and Proliferation on Ti Using Direct
      Current Stimulation.
AB  - Our objective was to establish an in vitro cell culture protocol to improve bone
      cell attachment and proliferation on Ti substrate using direct current
      stimulation. For this purpose, a custom made electrical stimulator was developed
      and a varying range of direct currents, from 5 to 25 uA, were used to study the
      current stimulation effect on bone cells cultured on conducting Ti samples in
      vitro. Cell-materials interaction was studied for a maximum of 5 days by
      culturing with human fetal osteoblast cells (hFOB). The direct current was
      applied in every 8 h time interval and the duration of electrical stimulation was
      kept constant at 15 min for all cases. In vitro results showed that direct
      current stimulation significantly favored bone cell attachment and proliferation
      in comparison to nonstimulated Ti surface. Immunochemistry and confocal
      microscopy results confirmed that the cell adhesion was most pronounced on 25 uA
      direct current stimulated Ti surfaces as hFOB cells expressed higher vinculin
      protein with increasing amount of direct current. Furthermore, MTT assay results
      established that cells grew 30% higher in number under 25 uA electrical
      stimulation as compared to nonstimulated Ti surface after 5 days of culture
      period. In this work we have successfully established a simple and cost effective
      in vitro protocol offering easy and rapid analysis of bone cell-materials
      interaction which can be used in promotion of bone cell attachment and growth on
      Ti substrate using direct current electrical stimulation in an in vitro model.

PMID- 23144533
TI  - Effects of Protein-Simulated Body Fluid Mixing Methods on Characteristics of Bone
      Like Mineral.
AB  - This study examined effects of protein mixing methods into modified simulated
      body fluid (mSBF) on the crystalline structure and morphology of bone-like
      mineral (BLM) coated on poly(lactic-co-glycolic acid) PLGA. Using bovine serum
      albumin (BSA) as a model protein, four sample groups were prepared: the N-BLM
      group was coated by soaking substrates in mSBF without BSA; the B-BLM group was
      coated by soaking in mSBF with BSA added immediately before soaking; the Ca-BLM
      group was coated by soaking in Ca-mSBF prepared by premixing BSA with a CaCl(2)
      solution before preparing the mSBF; the P-BLM group was coated by soaking in P
      mSBF made by premixing the BSA with a KH(2)PO(4) solution. The B-BLM and Ca-BLM
      groups exhibited densely coated, thick BLM layers, whereas the P-BLM group
      exhibited loosely connected BLM clusters. The hydroxyapatite (HAp) crystallites
      of the B-BLM and Ca-BLM groups were aligned along the c-axis, but those of the P
      BLM group were disordered and had a lower crystallinity. The alignment to the c
      axis of Ca-BLM and the disordered orientation of P-BLM was caused by calcium ions
      bound to BSA in Ca-mSBF and phosphate ions bound to BSA in P-mSBF, respectively.
      These results show that the crystallinity and morphology of BLM can be controlled
      by the mixing of BSA in mSBF. The crystallinity of BLM is closely connected to
      its solubility. Therefore, the release characteristics of growth factors and cell
      regulation on BLM could be affected by the changes in the crystalinity of BLM.

PMID- 23144534
TI  - Control of Fusarium wilt in banana with Chinese leek.
AB  - The inhibitory effects of Chinese leek(Allium tuberosum) on Fusarium oxysporum f.
      sp. cubense (Foc) and on Fusarium wilt incidence were studied in order to
      identify a potential efficient way to control the disease. Adopting the rotation
      system of Chinese leek-banana reduced the Fusarium wilt incidence and disease
      severity index by 88 %-97 % and 91 %-96 %, respectively, improved the crop value
      by 36 %-86 %, in an area heavily infested by Foc between 2007 and 2009. As a
      result of inoculation in the greenhouse, Chinese leek treatment reduced disease
      incidence and the disease severity index by 58 % and 62 %, respectively in the
      variety Baxi (AAA) and by 79 % and 81 %, respectively in the variety Guangfen
      NO.1 (ABB). Crude extracts of Chinese leek completely inhibited the growth of Foc
      race 4 on Petri dishes, suppressed the proliferation of the spores by 91 % and
      caused 87 % spore mortality. The findings of this study suggest that Chinese leek
      has the potential to inhibit Foc growth and Fusarium wilt incidence. This
      potential may be developed into an environmentally friendly treatment to control
      Fusarium wilt of banana.

PMID- 23144535
TI  - The Instrument Set for Generating Fast Adiabatic Passage.
AB  - The design and construction of a high-performance, low-cost, and easy to assemble
      adiabatic extension set for homebuilt and commercial spectrometers is described.
      Described apparatus set was designed for the fast adiabatic passage generation
      and is based on direct digital synthesizer DDS. This solution gives generator
      high signal to noise ratio, phase stability even during frequency change which is
      only possible in expansive commercial high-end hardware. Critical synchronization
      and timing issues are considered and solutions are discussed. Different
      experimental conditions and techniques for the measurements are briefly
      discussed. The proposed system is very flexible and might be used for the
      measurement of low-frequency nuclear magnetic resonance.

PMID- 23144536
TI  - EPR Studies of DOPA-Melanin Complexes with Netilmicin and Cu(II) at Temperatures
      in the Range of 105-300 K.
AB  - The application of electron paramagnetic resonance (EPR) spectroscopy in pharmacy
      of melanin complexes with netilmicin and Cu(II) was presented. The continuous
      microwave saturation of EPR spectra of DOPA-melanin and the complexes was
      performed. EPR spectra were measured on an X-band (9.3 GHz) spectrometer at
      temperatures in the range of 105-300 K. Paramagnetic copper ions decrease the
      intensity of the EPR lines of melanin's free radicals. It was found that fast
      spin-lattice relaxation characterizes DOPA-melanin-Cu(II) complexes. Slow spin
      lattice relaxation processes exist in melanin's paramagnetic centers of DOPA
      melanin and DOPA-melanin-netilmicin, [DOPA-melanin-netilmicin]-Cu(II), [DOPA
      melanin-Cu(II)]-netilmicin complexes. Spin-lattice relaxation processes are
      faster at higher temperatures. The homogeneous broadening of EPR lines for
      melanin complexes was observed. The practical consequences of differences between
      paramagnetic properties of melanin complexes with netilmicin and the complexes
      with Cu(II) were discussed.

PMID- 23144537
TI  - Cross-validation of theoretically quantified fiber continuum generation and
      absolute pulse measurement by MIIPS for a broadband coherently controlled optical
      source.
AB  - The predicted spectral phase of a fiber continuum pulsed source rigorously
      quantified by the scalar generalized nonlinear Schrodinger equation is found to
      be in excellent agreement with that measured by multiphoton intra-pulse
      interference phase scan (MIIPS) with background subtraction. This cross
      validation confirms the absolute pulse measurement by MIIPS and the transform
      limited compression of the fiber continuum pulses by the pulse shaper performing
      the MIIPS measurement, and permits the subsequent coherent control on the fiber
      continuum pulses by this pulse shaper. The combination of the fiber continuum
      source with the MIIPS-integrated pulse shaper produces compressed transform
      limited 9.6 fs (FWHM) pulses or arbitrarily shaped pulses at a central wavelength
      of 1020 nm, an average power over 100 mW, and a repetition rate of 76 MHz. In
      comparison to the 229-fs pump laser pulses that generate the fiber continuum, the
      compressed pulses reflect a compression ratio of 24.

PMID- 23144538
TI  - NRF2 molecule of the month.

PMID- 23144540
TI  - Building gene co-expression networks using transcriptomics data for systems
      biology investigations: Comparison of methods using microarray data.
AB  - Gene co-expression networks (GCN), built using high-throughput gene expression
      data are fundamental aspects of systems biology. The main aims of this study were
      to compare two popular approaches to building and analysing GCN. We use real
      ovine microarray transcriptomics datasets representing four different treatments
      with Metyrapone, an inhibitor of cortisol biosynthesis. We conducted several
      microarray quality control checks before applying GCN methods to filtered
      datasets. Then we compared the outputs of two methods using connectivity as a
      criterion, as it measures how well a node (gene) is connected within a network.
      The two GCN construction methods used were, Weighted Gene Co-expression Network
      Analysis (WGCNA) and Partial Correlation and Information Theory (PCIT) methods.
      Nodes were ranked based on their connectivity measures in each of the four
      different networks created by WGCNA and PCIT and node ranks in two methods were
      compared to identify those nodes which are highly differentially ranked (HDR). A
      total of 1,017 HDR nodes were identified across one or more of four networks. We
      investigated HDR nodes by gene enrichment analyses in relation to their
      biological relevance to phenotypes. We observed that, in contrast to WGCNA
      method, PCIT algorithm removes many of the edges of the most highly
      interconnected nodes. Removal of edges of most highly connected nodes or hub
      genes will have consequences for downstream analyses and biological
      interpretations. In general, for large GCN construction (with > 20000 genes)
      access to large computer clusters, particularly those with larger amounts of
      shared memory is recommended.

PMID- 23144539
TI  - Homology modeling, simulation and molecular docking studies of catechol-2, 3
      Dioxygenase from Burkholderia cepacia: Involved in degradation of Petroleum
      hydrocarbons.
AB  - Catechol 2, 3-dioxygenase is present in several types of bacteria and undergoes
      degradation of environmental pollutants through an important key biochemical
      pathways. Specifically, this enzyme cleaves aromatic rings of several
      environmental pollutants such as toluene, xylene, naphthalene and biphenyl
      derivatives. Hence, the importance of Catechol 2, 3-dioxygenase and its role in
      the degradation of environmental pollutants made us to predict the three
      dimensional structure of Catechol 2, 3-dioxygenase from Burkholderia cepacia. The
      10ns molecular dynamics simulation was carried out to check the stability of the
      modeled Catechol 2, 3- dioxygenase. The results show that the model was
      energetically stable, and it attains their equilibrium within 2000 ps of
      production MD run. The docking of various petroleum hydrocarbons into the
      Catechol 2,3-dioxygenase reveals that the benzene, O-xylene, Toluene, Fluorene,
      Naphthalene, Carbazol, Pyrene, Dibenzothiophene, Anthracene, Phenanthrene,
      Biphenyl makes strong hydrogen bond and Van der waals interaction with the active
      site residues of H150, L152, W198, H206, H220, H252, I254, T255, Y261, E271, L276
      and F309. Free energy of binding and estimated inhibition constant of these
      compounds demonstrates that they are energetically stable in their binding
      cavity. Chrysene shows positive energy of binding in the active site atom of Fe.
      Except Pyrene all the substrates made close contact with Fe atom by the distance
      ranges from 1.67 to 2.43 A. In addition to that, the above mentioned substrate
      except pyrene all other made pi-pi stacking interaction with H252 by the distance
      ranges from 3.40 to 3.90 A. All these docking results reveal that, except
      Chrysene all other substrate has good free energy of binding to hold enough in
      the active site and makes strong VdW interaction with Catechol-2,3-dioxygenase.
      These results suggest that, the enzyme is capable of catalyzing the above
      mentioned substrate.

PMID- 23144541
TI  - Phylogenetic study of nine species of freshwater monogeneans using secondary
      structure and motif prediction from India.
AB  - The present study was performed to identify and validate monogenean species from
      different piscine hosts using molecular tools. Nine species of freshwater
      monogeneans were collected from gills and skin of freshwater fishes at
      Hastinapur, Meerut, India. After microscopic examination, molecular analysis was
      performed utilizing 28S gene marker. Phylogenetic analysis indicated the
      validation and systematic position of these nine different monogeneans belongs to
      the Dactylogyridae and Gyrodactylidae families. The findings also confirm that
      the 28S rDNA sequence is highly conserved and may prove to be useful in taxonomic
      studies of parasitic platyhelminthes. Besides this, the study is also
      supplemented by molecular morphometrics that is based on 28S secondary structure
      homologies of nine monogenean species. The data indicate that 28S motifs i.e., <=
      50bp in size can also be considered a promising tool for monogenean species
      identification and their validation.

PMID- 23144542
TI  - Prediction of antiviral peptides derived from viral fusion proteins potentially
      active against herpes simplex and influenza A viruses.
AB  - There are very few antiviral drugs available to fight viral infections and the
      appearance of viral strains resistant to these antivirals is not a rare event.
      Hence, the design of new antiviral drugs is important. We describe the prediction
      of peptides with antiviral activity (AVP) derived from the viral glycoproteins
      involved in the entrance of herpes simplex (HSV) and influenza A viruses into
      their host cells. It is known, that during this event viral glycoproteins suffer
      several conformational changes due to protein-protein interactions, which lead to
      membrane fusion between the viral envelope and the cellular membrane. Our
      hypothesis is that AVPs can be derived from these viral glycoproteins,
      specifically from regions highly conserved in amino acid sequences, which at the
      same time have the physicochemical properties of being highly exposed
      (antigenic), hydrophilic, flexible, and charged, since these properties are
      important for protein-protein interactions. For that, we separately analyzed the
      HSV glycoprotein H and B, and influenza A viruses hemagglutinin (HA), using
      several bioinformatics tools. A set of multiple alignments was carried out, to
      find the most conserved regions in the amino acid sequences. Then, the
      physicochemical properties indicated above were analyzed. We predicted several
      peptides 12-20 amino acid length which by docking analysis were able to interact
      with the fusion viral glycoproteins and thus may prevent conformational changes
      in them, blocking the viral infection. Our strategy to design AVPs seems to be
      very promising since the peptides were synthetized and their antiviral activities
      have produced very encouraging results.

PMID- 23144543
TI  - Computational validation of 3-ammonio-3-(4-oxido- 1H-imidazol-1-ium-5-yl) propane
      1, 1-bis (olate) as a potent anti-tubercular drug against mt-MetAP.
AB  - The advent of Multi Drug Resistant (MDR) strain of Mycobacterium tuberculosis
      (TB) necessitated search for new drug targets for the bacterium. It is reported
      that 3.3% of all new tuberculosis cases had multidrug resistance (MDR-TB) in 2009
      and each year, about 0.44 million MDR-TB cases are estimated to emerge and 0.15
      million people with MDR-TB die. Keeping such an alarming situation under
      consideration we wanted to design suitable anti tubercular molecules for new
      target using computational tools. In the work Methionine aminopeptidase (MetAP)
      of Mycobacterium tuberculosis was considered as target and three non-toxic
      phenolic=ketonic compounds were considered as ligands. Docking was done with Flex
      X and AutoDock 4.2 separately. Ten proven inhibitors of MetAP were collected from
      literature with their IC50 and were correlated using EasyQSAR to generate QSAR
      model. Activity of ligands in question was predicted from QSAR. Pharmacophore for
      each docking was generated using Ligandscout 3.0. Toxicity of the ligands in
      question was predicted on Mobyle@rpbs portal and Actelion property explorer.
      Molecular docking with target showed that of all three ligands, 3-ammonio-3-(4
      oxido-1H-imidazol-1-ium-5-yl) propane-1, 1-bis (olate) has highest affinity (-
      37.5096) and lowest IC50 (4.46 uM). We therefore, propose that -3-ammonio-3-(4
      oxido-1H-imidazol-1-ium-5-yl) propane-1,1- bis(olate) as a potent MetAP inhibitor
      may be a new anti-tubercular drug particularly in the context of Multi Drug
      Resistant Tuberculosis (MDR-TB).

PMID- 23144544
TI  - Molecular Dynamics Simulation of Rap1 Myb-type domain in Saccharomyces
      cerevisiae.
AB  - Telomere is a nucleoprotein complex that plays important role in stability and
      their maintenance and consists of random repeats of species specific motifs. In
      budding Saccharomyces cerevisiae, Repressor Activator Protein 1 (Rap1) is a
      sequence specific protein that involved in transcriptional regulation. Rap1
      consist of three active domains like N-terminal BRCT-domain, DNA-binding domain
      and C-terminal RCT-domain. In this study the unknown 3D structure of Myb-type
      domain (having 61 residues) within DNAbinding domain was modeled by Modeller7,
      and verified using different online bioinformatics tools (ProCheck, WhatIf,
      Verify3D). Dynamics of Myb-type domain of Rap1was carried out through simulation
      studies using GROMACS software. Time dependent interactions among the molecules
      were analyzed by Root Mean Square Deviation (RMSD), Radius of Gyration (Rg) and
      Root Mean Square Fluctuation (RMSF) plots. Motional properties in reduced
      dimension were also performed by Principal Component Analysis (PCA). Result
      indicated that Rap1 interacts with DNA major groove through its Helix Turn Helix
      motifs. Helix 3 was rigid, less amount of fluctuation was found as it interacts
      with DNA major groove. Helix2 and N-terminal having considerable fluctuation in
      the time scale.

PMID- 23144545
TI  - Computational predictions of common transcription factor binding sites on the
      genes of proline metabolism in plants.
AB  - Proline, an imino acid, has been well documented to be associated with the stress
      response induced by abiotic factors such as drought, cold and salinity in plants
      and biotic factors such as bacterial and fungal attacks. However, the regulatory
      mechanisms controlling proline metabolism, intercellular and intracellular
      transport and connections of proline to other metabolic pathways are poorly
      understood. F-MATCH analysis combined with composite module analysis (CMA)
      revealed that the binding sites matching matrices for O2 and OCSBF-1 were
      overrepresented in the promoters of differentially expressed proline metabolism
      genes. The presence of MYBAS1 consensus binding sites occurring in combination
      with O2 and OCSBF1 in the promoters of genes of proline biosynthesis pathway and
      SBF1 and GT1 consensus binding sites occurring in combination with O2 and OCSBF1
      in the promoters of proline catabolic pathway genes suggest their involvement in
      modulation of proline metabolism and its accumulation in plants.

PMID- 23144546
TI  - Physicochemical characterization and functional analysis of some snake venom
      toxin proteins and related non-toxin proteins of other chordates.
AB  - Snake venom contains a diverse array of proteins and polypeptides. Cytotoxins and
      short neurotoxins are non-enzymatic polypeptide components of snake venom. The
      three-dimensional structure of cytotoxin and short neurotoxin resembles a three
      finger appearance of three-finger protein super family. Different family members
      of three-finger protein super family are employed in diverse biological
      functions. In this work we analyzed the cytotoxin, short neurotoxin and related
      non-toxin proteins of other chordates in terms of functional analysis, amino acid
      compositional (%) profile, number of amino acids, molecular weight, theoretical
      isoelectric point (pI), number of positively charged and negatively charged amino
      acid residues, instability index and grand average of hydropathy with the help of
      different bioinformatical tools. Among all interesting results, profile of amino
      acid composition (%) depicts that all sequences contain a conserved cysteine
      amount but differential amount of different amino acid residues which have a
      family specific pattern. Involvement in different biological functions is one of
      the driving forces which contribute the vivid amino acid composition profile of
      these proteins. Different biological system dependent adaptation gives the birth
      of enriched bio-molecules. Understanding of physicochemical properties of these
      proteins will help to generate medicinally important therapeutic molecules for
      betterment of human lives.

PMID- 23144547
TI  - Molecular docking analyses of Avicennia marinaderived phytochemicals against
      white spot syndrome virus (WSSV) envelope protein-VP28.
AB  - White spot syndrome (WSS) is one of the most common and most disastrous diseases
      of shrimp worldwide. It causes up to 100% mortality within 3 to 4 days in
      commercial shrimp farms, resulting in large economic losses to the shrimp farming
      industry. VP28 envelope protein of WSSV is reported to play a key role in the
      systemic infection in shrimps. Considering the most sombre issue of viral disease
      in cultivated shrimp, the present study was undertaken to substantiate the
      inhibition potential of Avicennia marinaderived phytochemicals against the WSSV
      envelope protein VP28. Seven A. marina-derived phytochemicals namely
      stigmasterol, triterpenoid, betulin, lupeol, avicenol-A, betulinic acid and
      quercetin were docked against the WSSV protein VP28 by using Argus lab molecular
      docking software. The chemical structures of the phytochemicals were retrieved
      from Pubchem database and generated from SMILES notation. Similarly the protein
      structure of the envelope protein was obtained from protein data bank (PDB-ID:
      2ED6). Binding sites were predicted by using ligand explorer software. Among the
      phytochemicals screened, stigmasterol, lupeol and betulin showed the best binding
      exhibiting the potential to block VP28 envelope protein of WSSV, which could
      possibly inhibit the attachment of WSSV to the host species. Further experimental
      studies will provide a clear understanding on the mode of action of these
      phytochemicals individually or synergistically against WSSV envelope protein and
      can be used as an inhibitory drug to reduce white spot related severe
      complications in crustaceans.

PMID- 23144548
TI  - Structure-based design of eugenol analogs as potential estrogen receptor
      antagonists.
AB  - Eugenol is an essential oil mainly found in the buds and leaves of clove
      (Syzygium aromaticum (L.) Merrill and Perry), which has been reported to have
      activity on inhibition of cell proliferation and apoptosis induction in human MCF
      7 breast cancer cells. This biological activity is correlated to its activity as
      an estrogen receptor antagonist. In this article, we present the construction and
      validation of structure-based virtual screening (SBVS) protocols to identify the
      potent estrogen receptor alpha (ER) antagonists. The selected protocol, which
      gave acceptable enrichment factors as a virtual screening protocol, subsequently
      used to virtually screen eugenol, its analogs and their dimers. Based on the
      virtual screening results, dimer eugenol of 4-[4-hydroxy-3-(prop-2-en-1-
      yl)phenyl]-2-(prop-2-en-1-yl)phenol is recommended to be developed further in
      order to discover novel and potent ER antagonists.

PMID- 23144549
TI  - Virtual screening of ABCC1 transporter nucleotidebinding domains as a therapeutic
      target in multidrug resistant cancer.
AB  - ABCC1 is a member of the ATP-binding Cassette super family of transporters,
      actively effluxes xenobiotics from cells. Clinically, ABCC1 expression is linked
      to cancer multidrug resistance. Substrate efflux is energised by ATP binding and
      hydrolysis at the nucleotide-binding domains (NBDs) and inhibition of these
      events may help combat drug resistance. The aim of this study is to identify
      potential inhibitors of ABCC1 through virtual screening of National Cancer
      Institute (NCI) compounds. A threedimensional model of ABCC1 NBD2 was generated
      using MODELLER whilst the X-ray crystal structure of ABCC1 NBD1 was retrieved
      from the Protein Data Bank. A pharmacophore hypothesis was generated based on
      flavonoids known to bind at the NBDs using PHASE, and used to screen the NCI
      database. GLIDE was employed in molecular docking studies for all hit compounds
      identified by pharmacophore screening. The best potential inhibitors were
      identified as compounds possessing predicted binding affinities greater than ATP.
      Approximately 5% (13/265) of the hit compounds possessed lower docking scores
      than ATP in ABCC1 NBD1 (NSC93033, NSC662377, NSC319661, NSC333748, NSC683893,
      NSC226639, NSC94231, NSC55979, NSC169121, NSC166574, NSC73380, NSC127738,
      NSC115534), whereas approximately 7% (7/104) of docked NCI compounds were
      predicted to possess lower docking scores than ATP in ABCC1 NBD2 (NSC91789,
      NSC529483, NSC211168, NSC318214, NSC116519, NSC372332, NSC526974). Analyses of
      docking orientations revealed P-loop residues of each NBD and the aromatic amino
      acids Trp653 (NBD1) and Tyr1302 (NBD2) were key in interacting with high-affinity
      compounds. On the basis of docked orientation and docking score the compounds
      identified may be potential inhibitors of ABCC1 and require further
      pharmacological analysis. ABBREVIATIONS: ABC - ATP-binding cassette, DHS -
      dehydrosilybin, MDR - multidrug resistance, NBD - nucleotide-binding domain, PDB 
      protein data bank.

PMID- 23144550
TI  - Gene interaction studies in cellular reprogramming of adult stem cells to
      embyronic like stem cells.
AB  - The sophisticated process of reprogramming of adult stem cells to embryonic-like
      stem cells, known as cellular reprogramming, involves the risk of generation of
      tumorigenic cells due to the complexity involved. Oct4 protein is the inevitable
      element for inducing pluripotency along with Sox2 and Nanog proteins. In this
      study, the set of genes interacting with Oct4, Sox2 and Nanog were analyzed and
      categorized based on their molecular function. Later, the domains of translated
      products of 46 transcription factors interacting with Oct4, Sox2 and Nanog were
      identified, clustered them based on the nature of the domain and multiple
      sequence alignment was performed to find any functionally important consensus
      regions in the sequence. The key finding of this study is the 13 member cluster
      of homeo domain transcription factors exhibited some consensus in their sequence.

PMID- 23144551
TI  - Cluster analysis identifies aminoacid compositional features that indicate
      Toxoplasma gondii adhesin proteins.
AB  - Toxoplasma gondii invade host cells using a multi-step process that depends on
      the regulated secretion of adhesions. To identify key primary sequence features
      of adhesins in this parasite, we analyze the relative frequency of individual
      amino acids, their dipeptide frequencies, and the polarity, polarizability and
      Van der Waals volume of the individual amino acids by using cluster analysis.
      This method identified cysteine as a key amino acid in the Toxoplasma adhesin
      group. The best vector algorithm of non-concatenated features was for 2
      attributes: the single amino acid relative frequency and the dipeptide frequency.
      Polarity, polarizability and Van der Waals volume were not good classificatory
      attributes. Single amino acid attributes clustered unambiguously 67 apicomplexan
      hypothetical adhesins. This algorithm was also useful for clustering hypothetical
      Toxoplasma target host receptors. All of the cluster performances had over 70%
      sensitivity and 80% specificity. Compositional aminoacid data can be useful for
      improving machine learning-based prediction software when homology and structural
      data are not sufficient.

PMID- 23144552
TI  - Design of potential siRNA molecules for T antigen gene silencing of Merkel Cell
      Polyomavirus.
AB  - Merkel cell carcinoma (MCC) is the most aggressive skin cancer. Recently, it was
      demonstrated that human Merkel cell polyomavirus (MCV) is clonally integrated in
      80% of MCC tumors. Genetic studies of MCV have shown that T antigen protein is
      responsible for replication of genome and play a foremost role in viral
      infection. Therefore, T antigen protein may be used as suitable target for
      disease diagnosis. Viral activity can be restrained through RNA interference
      (RNAi) technology, an influential method for post transcriptional gene silencing
      in a sequence specific manner. In current study four effective siRNA molecules
      for silencing of MCV were rationally designed and validated using computational
      methods, which may lead to knockdown the activity of virus. Thus, this approach
      may provide an insight for the chemical synthesis of antiviral RNA molecule for
      the treatment of MCC at genome level.

PMID- 23144553
TI  - Computational finding of potential inhibitor for Cytochrome P450 Mono-oxygenases
      Enzyme of Mycobacterium tuberculosis.
AB  - Cytochrome P450 mono-oxygenases (2UUQ) enzyme from Mycobacterium tuberculosis
      catalyzes oxidation of organic compounds such as lipids and steroidal hormones
      therefore remain as potential drug target. Currently available first line anti
      tuberculosis drugs have been caused several side effects in the body as well as
      resistance development by mycobacterium against these drugs, necessitates the
      considerable need for finding new drugs. Therefore, we propose a structure based
      computational method to find a new potential inhibitor for cytochrome P450 mono
      oxygenases enzyme. Compounds from several ligand databases were docked against
      the functional sites of 2UUQ (A) through the standard GEMDOCK v2.0 and
      AUTODOCK4.0 molecular docking tools. Commercially available chemical compound
      ZINC00004165 (5-[3-(2-nitroimidazol-1-yl) propyl] phenanthridine) has produced
      top rank with lowest interaction energy of -113.2 (via GEMDOCK) and lowest
      docking energy of -9.80 kcal/mol (via AUTODOCK) as compared to first line anti TB
      compounds. Z score and normal distribution analysis verified that the
      ZINC00004165 compound has more affinity towards 2UUQ in comparison to large
      number of random population of compounds. ZINC00004165 is also in agreement with
      the drug likeness properties of Lipinski rule of five without any violation.
      Therefore, our finding concludes that the commercial compound ZINC00004165 can
      act as a potential inhibitor against cytochrome P450 mono-oxygenases enzyme of
      Mycobacterium tuberculosis.

PMID- 23144554
TI  - Niche specific amino acid features within the core genes of the genus Shewanella.
AB  - Shewanella species are found to dwell in various ecological niches. The
      widespread habitation where they live requires specific adaptations. Recent
      advances in genomic approaches, such as in sequencing technologies, generate huge
      amount of genomic data that lend support towards understanding the microbial
      evolution and diversity through comparative study. In this manuscript, we discuss
      a comparative analysis of core genes of phylogenetically related twelve members
      from the genus Shewanella. Phylogenetic analysis based on the core genes,
      differentiated two subgroups of the genus, one group comprises of species
      characterized as highpressure cold-adapted while the other group is characterized
      as mesophilic pressure-sensitive species. By analyzing the differences of amino
      acid composition of these two groups, we have identified the specific trend of
      amino acid usage that has been adopted by the psychro-peizo-tolerant Shewanella
      species. The functional categories have also been recognized which are
      responsible for rendering the particular amino acid compositional pattern in
      psychropeizophilic Shewanella species facilitating their niche adaptation.

PMID- 23144555
TI  - Structural characterization of a flavonoid glycosyltransferase from Withania
      somnifera.
AB  - Medicinal plants are extensively utilized in traditional and herbal medicines,
      both in India and around the world due to the presence of diverse low molecular
      weight natural products such as flavonoids, alkaloids, terpenoids and sterols.
      Flavonoids which have health benefits for humans are the large class of
      phenylpropanoid-derived secondary metabolites and are mostly glycosylated by UDP
      glycosyltransferases (UGTs). Although large numbers of different UGTs are known
      from higher plants, very few protein structures have been reported till now. In
      the present study, the three-dimensional model of flavonoid specific
      glycosyltransferases (WsFGT) from Withania somnifera was constructed based on the
      crystal structure of plant UGTs. The resulted model was assessed by various tools
      and the final refined model revealed GT-B type fold. Further, to understand the
      sugar donors and acceptors interactions with the active site of WsFGT, docking
      studies were performed. The amino acids from conserved PSPG box were interacted
      with sugar donor while His18, Asp110, Trp352 and Asn353 were important for
      catalytic function. This structural and docking information will be useful to
      understand the glycosylation mechanism of flavonoid glucosides. ABBREVIATIONS:
      DOPE - Discrete Optimized Potential Energy, PDB - Protein Data Bank, PSPG - Plant
      Secondary Product Glycosyltransferase, RMSD - Root Mean Squared Deviation, UDP -
      Uridine diphosphate, UGT - UDP-glycosyltransferases.

PMID- 23144556
TI  - RKN Lethal DB: A database for the identification of Root Knot Nematode
      (Meloidogyne spp.) candidate lethal genes.
AB  - Root Knot nematode (RKN; Meloidogyne spp.) is one of the most devastating
      parasites that infect the roots of hundreds of plant species. RKN cannot live
      independently from their hosts and are the biggest contributors to the loss of
      the world's primary foods. RNAi gene silencing studies have demonstrated that
      there are fewer galls and galls are smaller when RNAi constructs targeted to
      silence certain RKN genes are expressed in plant roots. We conducted a
      comparative genomics analysis, comparing RKN genes of six species: Meloidogyne
      Arenaria, Meloidogyne Chitwoodi, Meloidogyne Hapla, Meloidogyne Incognita,
      Meloidogyne Javanica, and Meloidogyne Paranaensis to that of the free living
      nematode Caenorhabditis elegans, to identify candidate genes that will be lethal
      to RKN when silenced or mutated. Our analysis yielded a number of such candidate
      lethal genes in RKN, some of which have been tested and proven to be effective in
      soybean roots. A web based database was built to house and allow scientists to
      search the data. This database will be useful to scientists seeking to identify
      candidate genes as targets for gene silencing to confer resistance in plants to
      RKN. AVAILABILITY: The database can be accessed from
      http://bioinformatics.towson.edu/RKN/

PMID- 23144557
TI  - Structure based function prediction of proteins using fragment library frequency
      vectors.
AB  - The function of the protein is primarily dictated by its structure. Therefore it
      is far more logical to find the functional clues of the protein in its overall 3
      dimensional fold or its global structure. In this paper, we have developed a
      novel Support Vector Machines (SVM) based prediction model for functional
      classification and prediction of proteins using features extracted from its
      global structure based on fragment libraries. Fragment libraries have been
      previously used for abintio modelling of proteins and protein structure
      comparisons. The query protein structure is broken down into a collection of
      short contiguous backbone fragments and this collection is discretized using a
      library of fragments. The input feature vector is frequency vector that counts
      the number of each library fragment in the collection of fragments by all-to-all
      fragment comparisons. SVM models were trained and optimised for obtaining the
      best 10-fold Cross validation accuracy for classification. As an example, this
      method was applied for prediction and classification of Cell Adhesion molecules
      (CAMs). Thirty-four different fragment libraries with sizes ranging from 4 to 400
      and fragment lengths ranging from 4 to 12 were used for obtaining the best
      prediction model. The best 10-fold CV accuracy of 95.25% was obtained for library
      of 400 fragments of length 10. An accuracy of 87.5% was obtained on an unseen
      test dataset consisting of 20 CAMs and 20 NonCAMs. This shows that protein
      structure can be accurately and uniquely described using 400 representative
      fragments of length 10.

PMID- 23144558
TI  - Use of bacteria for rapid, pH-neutral, hydrolysis of the model hydrophobic
      carboxylic acid ester p-nitrophenyl picolinate.
AB  - Caulobacter crescentus, Escherichia coli and Bacillus subtilis cultures promote
      the hydrolysis of the model ester p-nitrophenyl picolinate (PNPP) at neutral pH
      with high efficiency. Hydrolysis is related to cell concentration, while the
      interaction of PNPP with both bacterial cells and their extracellular molecules
      is required for a maximum rate of PNPP hydrolysis in C. crescentus cultures.
      Furthermore, C. crescentus cultures hydrolyze PNPP at concentrations useful in
      synthetic chemistry.

PMID- 23144559
TI  - Cognitive-Behavioral Therapy for Depression in an Older Gay Man: A Clinical Case
      Study.
AB  - Although strong evidence supports cognitive-behavioral therapy for late-life
      depression and depression in racial and ethnic minorities, there are no empirical
      studies on the treatment of depression in older sexual minorities. Three distinct
      literatures were tapped to create a depression treatment protocol for an older
      gay male. Interventions were deduced from the late-life depression literature,
      culturally adapted CBT protocols for racial minorities, and the emerging social
      and developmental psychological theories for lesbian, gay, and bisexual
      populations. Specific treatment interventions, processes, and outcomes are
      described to illustrate how these literatures may be used to provide more
      culturally appropriate and effective health care for the growing, older sexual
      minority population.

PMID- 23144560
TI  - Embedding resorcinarene cavitands in lipid vesicles().
AB  - A fluorescently labeled resorcinarene cavitand has been successfully embedded in
      DLPC lipid vesicles and imaged using confocal microscopy. The cavitand resides
      exclusively in the bilayer.

PMID- 23144562
TI  - Nanobarcoding: detecting nanoparticles in biological samples using in situ
      polymerase chain reaction.
AB  - BACKGROUND: Determination of the fate of nanoparticles (NPs) in a biological
      system, or NP biodistribution, is critical in evaluating an NP formulation for
      nanomedicine. Current methods to determine NP biodistribution are greatly
      inadequate, due to their limited detection thresholds. Herein, proof of concept
      of a novel method for improved NP detection based on in situ polymerase chain
      reaction (ISPCR), coined "nanobarcoding," is demonstrated. METHODS: Nanobarcoded
      superparamagnetic iron oxide nanoparticles (NB-SPIONs) were characterized by
      dynamic light scattering, zeta potential, and hyperspectral imaging measurements.
      Cellular uptake of Cy5-labeled NB-SPIONs (Cy5-NB-SPIONs) was imaged by confocal
      microscopy. The feasibility of the nanobarcoding method was first validated by
      solution-phase PCR and "pseudo"-ISPCR before implementation in the model in vitro
      system of HeLa human cervical adenocarcinoma cells, a cell line commonly used for
      ISPCR-mediated detection of human papilloma virus (HPV). RESULTS: Dynamic light
      scattering measurements showed that NB conjugation stabilized SPION size in
      different dispersion media compared to that of its precursor, carboxylated SPIONs
      (COOH-SPIONs), while the zeta potential became more positive after NB
      conjugation. Hyperspectral imaging confirmed NB conjugation and showed that the
      NB completely covered the SPION surface. Solution-phase PCR and pseudo-ISPCR
      showed that the expected amplicons were exclusively generated from the NB-SPIONs
      in a dose-dependent manner. Although confocal microscopy revealed minimal
      cellular uptake of Cy5-NB-SPIONs at 50 nM over 24 hours in individual cells,
      ISPCR detected definitive NB-SPION signals inside HeLa cells over large sample
      areas. CONCLUSION: Proof of concept of the nanobarcoding method has been
      demonstrated in in vitro systems, but the technique needs further development
      before its widespread use as a standardized assay.

PMID- 23144563
TI  - Ceruloplasmin and iron in Alzheimer's disease and Parkinson's disease: a synopsis
      of recent studies.
AB  - Ceruloplasmin (Cp) concentration and oxidative activity in serum are lowered in
      Parkinson's disease (PD). In most PD patients, iron increases in the substantia
      nigra in the midbrain. In PD, the low Cp concentration and activity in serum and
      the high iron amounts in the substantia nigra appears to be correlated. An
      hereditary background is common in PD and variations in the Cp gene that have
      been found in PD are associated with high iron levels in the substantia nigra.
      Variations in Cp synthesis and in the incorporation of copper into the Cp
      molecule are essential features of PD. In Alzheimer's disease (AD), the Cp
      activity in serum is lowered but not the concentration, except in the advanced
      stages of the disease. Generally, iron is not increased in the AD brain. In the
      AD brain, iron accumulates in neuritic plaques and in neurofibrillary tangles.
      There is also increased risk of iron-mediated tissue damage, which may possibly
      be counteracted by Cp. At the same time, the AD brain is short in copper, which
      presumably results in the deficient activity of many copper enzymes in the brain,
      in addition to Cp. Lowered Cp activity in serum most likely stems from lessened
      incorporation of copper in the Cp molecule and similar incorporation defects
      might also apply to other copper enzymes in AD.

PMID- 23144561
TI  - The role of surface charge in cellular uptake and cytotoxicity of medical
      nanoparticles.
AB  - Many types of nanoparticles (NPs) are tested for use in medical products,
      particularly in imaging and gene and drug delivery. For these applications,
      cellular uptake is usually a prerequisite and is governed in addition to size by
      surface characteristics such as hydrophobicity and charge. Although positive
      charge appears to improve the efficacy of imaging, gene transfer, and drug
      delivery, a higher cytotoxicity of such constructs has been reported. This review
      summarizes findings on the role of surface charge on cytotoxicity in general,
      action on specific cellular targets, modes of toxic action, cellular uptake, and
      intracellular localization of NPs. Effects of serum and intercell type
      differences are addressed. Cationic NPs cause more pronounced disruption of
      plasma-membrane integrity, stronger mitochondrial and lysosomal damage, and a
      higher number of autophagosomes than anionic NPs. In general, nonphagocytic cells
      ingest cationic NPs to a higher extent, but charge density and hydrophobicity are
      equally important; phagocytic cells preferentially take up anionic NPs. Cells do
      not use different uptake routes for cationic and anionic NPs, but high uptake
      rates are usually linked to greater biological effects. The different uptake
      preferences of phagocytic and nonphagocytic cells for cationic and anionic NPs
      may influence the efficacy and selectivity of NPs for drug delivery and imaging.

PMID- 23144564
TI  - Targeted treatments for cervical cancer: a review.
AB  - Cervical cancer is the second most common cause of cancer death in women
      worldwide and the development of new diagnosis, prognostic, and treatment
      strategies merits special attention. Although surgery and chemoradiotherapy can
      cure 80%-95% of women with early stage cancer, the recurrent and metastatic
      disease remains a major cause of cancer death. Many efforts have been made to
      design new drugs and develop gene therapies to treat cervical cancer. In recent
      decades, research on treatment strategies has proposed several options, including
      the role of HPV E6 and E7 oncogenes, which are retained and expressed in most
      cervical cancers and whose respective oncoproteins are critical to the induction
      and maintenance of the malignant phenotype. Other efforts have been focused on
      antitumor immunotherapy strategies. It is known that during the development of
      cervical cancer, a cascade of abnormal events is induced, including disruption of
      cellular cycle control, perturbation of antitumor immune response, alteration of
      gene expression, and deregulation of microRNA expression. Thus, in this review
      article we discuss potential targets for the treatment of cervical cancer
      associated with HPV infection, with special attention to immunotherapy
      approaches, clinical trials, siRNA molecules, and their implications as gene
      therapy strategies against cervical cancer development.

PMID- 23144565
TI  - Cost-effectiveness of candesartan versus losartan in the primary preventive
      treatment of hypertension.
AB  - BACKGROUND: Although angiotensin receptor blockers have different receptor
      binding properties, no comparative randomized studies with cardiovascular event
      endpoints have been performed for this class of drugs. The aim of this study was
      to assess the long-term cost-effectiveness of candesartan (Atacand((r))) versus
      generic losartan in the primary preventive treatment of hypertension. METHODS: A
      decision-analytic model was developed to estimate costs and health outcomes over
      a patient's lifetime. Data from a clinical registry study were used to estimate
      event rates for cardiovascular complications, such as myocardial infarction and
      heart failure. Costs and quality of life data were from published sources. Costs
      were in Swedish kronor and the outcome was quality-adjusted life-years (QALYs).
      RESULTS: Due to reduced rates of cardiovascular complications, candesartan was
      associated with a QALY gain and lower health care costs compared with generic
      losartan (0.053 QALYs gained and reduced costs of approximately 4700 Swedish
      kronor for women; and 0.057 QALYs gained and reduced costs of approximately 4250
      Swedish kronor for men). This result was robust in several sensitivity analyses.
      CONCLUSION: When modeling costs and health outcomes based on event rates for
      cardiovascular complications from a real-world registry study, candesartan
      appears to bring a QALY gain and a reduction in costs compared with generic
      losartan in the primary preventive treatment of hypertension in Sweden.

PMID- 23144568
TI  - Size surprise? Tumour size, nodal status, and outcome after breast cancer.

PMID- 23144567
TI  - Epidural analgesia for labor: Current techniques.
AB  - Epidural analgesia is an extremely effective and popular treatment for labor
      pain. In this review, we trace the history of the use of epidural analgesia and
      its refinements. We then outline the goals of treatment and methods used to
      attain those goals. The use of low concentrations of local anesthetics, combined
      with lipid-soluble opioids, does not impede the progress of labor or depress the
      newborn. The incidence of side effects is low. Maintenance of analgesia that
      allows patient control enhances patient satisfaction.

PMID- 23144569
TI  - The african organization for research and training in cancer.

PMID- 23144570
TI  - The african organization for research and training in cancer.

PMID- 23144571
TI  - Are bilateral cancers hereditary? Part II.

PMID- 23144572
TI  - Tumour size predicts long-term survival among women with lymph node-positive
      breast cancer.
AB  - BACKGROUND: The benefit of early detection of breast cancer is assumed to be
      achieved primarily by identifying disease before it has spread beyond the breast.
      In support of early detection, the survival experience of women with breast
      cancer decreases as the mean size of the cancer increases. It is not clear if
      women with regional spread (node-positive breast cancer) benefit from early
      detection to the same extent that women with node-negative breast cancer do.
      METHODS: A review was conducted of the survival experience of 1894 patients with
      invasive breast cancers 5.0 cm or less in size. Cases were divided into node
      positive and node-negative, and tumours were categorized by size (0.1-1.0 cm, 1.1
      2.0 cm, and 2.1-5.0 cm). After a mean follow-up of 9.9 years, 368 cancer-specific
      deaths had occurred in the cohort. The effect of tumour size on 15-year survival
      for subgroups of women with node-positive and node-negative breast cancer was
      estimated. RESULTS: Tumour size was a strong predictor of 15-year survival in
      both the node-positive and node-negative cancer subgroups. A decline of 1.0 cm in
      size was associated with a reduction in 15-year mortality of 10.3% in the node
      positive group and of 2.5% in the node-negative group. A decline of approximately
      1.5 cm was associated with a reduction in mortality of 23.0% in the node-positive
      group and of 10.8% in the node-negative group. CONCLUSIONS: The impact of
      decreasing tumour size on 15-year survival is much greater for women with node
      positive than for women with node-negative breast cancers. Contrary to
      expectation, the benefit of screening is likely to be greater for women with
      relatively advanced breast cancer than for women with earlystage disease.

PMID- 23144566
TI  - Clinical applications of schizophrenia genetics: genetic diagnosis, risk, and
      counseling in the molecular era.
AB  - Schizophrenia is a complex neuropsychiatric disease with documented clinical and
      genetic heterogeneity, and evidence for neurodevelopmental origins. Driven by new
      genetic technologies and advances in molecular medicine, there has recently been
      concrete progress in understanding some of the specific genetic causes of this
      serious psychiatric illness. In particular, several large rare structural
      variants have been convincingly associated with schizophrenia, in targeted
      studies over two decades with respect to 22q11.2 microdeletions, and more
      recently in large-scale, genome-wide case-control studies. These advances promise
      to help many families afflicted with this disease. In this review, we critically
      appraise recent developments in the field of schizophrenia genetics through the
      lens of immediate clinical applicability. Much work remains in translating the
      recent surge of genetic research discoveries into the clinic. The epidemiology
      and basic genetic parameters (such as penetrance and expression) of most genomic
      disorders associated with schizophrenia are not yet well characterized. To date,
      22q11.2 deletion syndrome is the only established genetic subtype of
      schizophrenia of proven clinical relevance. We use this well-established
      association as a model to chart the pathway for translating emerging genetic
      discoveries into clinical practice. We also propose new directions for research
      involving general genetic risk prediction and counseling in schizophrenia.

PMID- 23144573
TI  - Clinical features and course of brain metastases in colorectal cancer: an
      experience from a single institution.
AB  - OBJECTIVES: Brain metastases from colorectal cancer (crc) are quite rare. Here,
      we review the characteristics, presentation, and clinical course of such patients
      at our institution. METHODS: We reviewed the medical records of patients with
      brain metastases from crc treated during 2000-2009. Associations between patient,
      tumour characteristics, treatment modality, and survival were assessed using the
      Kaplan-Meier method. RESULTS: We identified 48 patients (25 men, 23 women) who
      developed brain metastases from crc. The median age at diagnosis of the brain
      metastases was 63 years (range: 37-84 years). In 23 of the patients (48%), the
      primary tumour occurred in the rectum. At diagnosis of brain metastases, 43
      patients (90%) also had other systemic metastases (mainly pulmonary and hepatic).
      The median interval between diagnosis of the primary tumour and of the brain
      metastases was 24 months. Median survival after a diagnosis of brain metastasis
      from crc was 4 months (range: 1-13 months). We observed substantially better
      survival (13 months, p < 0.001) in patients treated with surgery followed by
      whole-brain radiotherapy (wbrt) than in those treated with radiotherapy or
      surgery alone. Sex, age, location and number of brain metastases, and timing of
      diagnosis did not affect survival. CONCLUSIONS: Brain metastases from crc develop
      late in the course of the disease, given that most patients already have other
      secondary lesions. Prognosis in these patients is poor, with those receiving
      treatment with surgery and wbrt having the best overall survival. Early detection
      and treatment of brain metastases with new systemic therapies may improve
      outcomes.

PMID- 23144574
TI  - Bone-targeted agents and skeletal-related events in breast cancer patients with
      bone metastases: the state of the art.
AB  - Most women with advanced breast cancer will develop bone metastases, which are
      associated with the development of skeletal-related events (sres) such as
      pathologic fractures and spinal cord compression. This article reviews the
      evolving definition and incidence of sres, the pathophysiology of bone
      metastases, and the key evidence for the safety and efficacy of the currently
      available systemic treatment options for preventing and delaying sres in the
      setting of breast cancer with bone metastases.The bisphosphonates are structural
      analogues of endogenous pyrophosphate; three of them (clodronate, pamidronate,
      and zoledronate) are currently approved for use in Canada in the setting of
      breast cancer with bone metastases. Denosumab is a fully human immunoglobulin G2
      monoclonal antibody that binds to human rankl (receptor activator of nuclear
      factor kappaB ligand), thereby preventing osteoclast formation, function, and
      survival, and reducing cancer-induced destruction of bone. Denosumab has recently
      been approved in Canada for reducing the risk of sres from the bone metastases
      associated with a variety of malignancies, including breast cancer. How to
      predict the patients that will benefit most from prophylactic treatment, the
      agents to select and the timing of switches between agents, the dosing schedules
      and durations of treatment to choose, the potential utility of the agents in the
      adjuvant setting, and the utility of additional endpoints such as markers of bone
      resorption are among the outstanding questions with respect to the optimal use of
      antiresorptive agents for patients with breast cancer and bone metastases.

PMID- 23144575
TI  - A first look at participation rates in cervical cancer screening programs in
      Canada.

PMID- 23144576
TI  - The African Organization for Research and Training in Cancer: historical
      perspective.
AB  - The African Organization for Research and Training in Cancer (aortic) is a
      bilingual (English and French) nonprofit organization dedicated to the promotion
      of cancer control and palliation in Africa. Its mission in respect to cancer
      control in Africa includes support of research and training;provision of relevant
      and accurate information on the prevention, early diagnosis, treatment, and
      palliation of cancer;promotion of public awareness about cancer and reduction of
      the stigma associated with it.In seeking to achieve its goal of cancer control in
      Africa, aortic strives to unite the continent and to make a positive impact
      throughout the region by collaboration with health ministries and global cancer
      organizations. The organization's key objectives are to further research relating
      to cancers prevalent in Africa, to support training programs in oncology for
      health care workers, to deal with the challenges of creating cancer control and
      prevention programs, and to raise public awareness of cancer in Africa. It also
      plans to organize symposia, workshops, meetings, and conferences that support its
      mission.Founded in September 1982, aortic was active only between 1983 (when its
      inaugural conference was held in the City of Lome, Togo, West Africa) and the
      late 1980s. The organization subsequently became inactive and moribund. In 2000,
      a group of expatriate African physicians and scientists joined in an effort with
      their non-African friends and colleagues to reactivate the dormant organization.
      Since its reactivation, aortic has succeeded in putting cancer on the public
      health agenda in many African countries by highlighting Africa's urgent need for
      cancer control and by holding meetings every two years in various African cities.
      National and international cancer control organizations worldwide have recognized
      the challenges facing Africa and have joined in aortic's mission.

PMID- 23144577
TI  - Time to put an end to the "one size fits all" approach to bisphosphonate use in
      patients with metastatic breast cancer?

PMID- 23144578
TI  - Malnutrition screening programs in adult cancer patients: clinical practice is
      hungry for evidence.

PMID- 23144579
TI  - Chemotherapy uptake and wait times in early-stage non-small-cell lung cancer.
AB  - BACKGROUND: Treatment uptake and elapsed times along the care path have emerged
      as potential quality indicators for cancer care delivery. This retrospective
      study examined changes in adjuvant chemotherapy uptake and elapsed times along
      the care path for patients in 2005 and in 2007 who had early-stage non-small-cell
      lung cancer (nsclc) and who underwent curative-intent surgery in Nova Scotia,
      Canada. METHODS: All patients who underwent curative-intent surgery for stages i
      iii nsclc in the two years of interest were included. Logistic regression and
      general linear models were used to examine factors associated with chemotherapy
      uptake patterns and, at various resolutions (low, intermediate, high), elapsed
      times between all care events in the care path. RESULTS: In the 223 patients who
      underwent curative-intent surgery (108 in 2005, 115 in 2007), several factors
      were associated with uptake patterns and elapsed times. Cohort year (2007 vs.
      2005) was not associated with referral to medical oncology [odds ratio (or):
      1.05; 95% confidence interval (ci): 0.51 to 2.15; p = 0.905], but it was
      associated with less treatment after referral (or: 0.34; 95% ci: 0.11 to 1.00; p
      = 0.057) and less overall uptake (or: 0.35; 95% ci: 0.13 to 0.95; p = 0.040).
      Patients were referred sooner to medical oncology in 2007 than in 2005 (21 days
      vs. 35 days, p = 0.008), but experienced longer waits between consultation and
      chemotherapy delivery (18 days vs. 7 days, p = 0.001). CONCLUSIONS: Significant
      differences were observed in care patterns over time. Frequent monitoring of care
      patterns at high resolution may optimize insights into emerging trends within
      cancer care systems.

PMID- 23144580
TI  - Evaluating the efficacy of current clinical practice of adjuvant chemotherapy in
      postmenopausal women with early-stage, estrogen or progesterone receptor
      positive, one-to-three positive axillary lymph node, breast cancer.
AB  - PURPOSE: We evaluated the benefit of the current clinical practice of adjuvant
      chemotherapy for postmenopausal women with early-stage, estrogen- or progesterone
      receptor-positive (er/pr+), one-to-three positive axillary lymph node (1-3 ln+),
      breast cancer (esbc). METHODS: Using the Manitoba Cancer Registry, we identified
      all postmenopausal women diagnosed with er/pr+ 1-3 ln+ esbc during the periods
      1995-1997, 2000-2002, and 2003-2005 (n = 156, 161, and 171 respectively).
      Treatment data were obtained from the Manitoba Cancer Registry and by linkage
      with Manitoba administrative databases. Seven-year survival data were available
      for the 1995-1997 and 2000-2002 populations. Using Cox regression, we assessed
      the independent effect of the clinical practice of adjuvant chemotherapy on
      disease-free (dfs) and overall survival (os). RESULTS: Clinical breast cancer
      treatments did not differ significantly between the 2000-2002 and 2003-2005
      populations. Adjuvant chemotherapy was administered in 103 patients in the 2000
      2002 population (64%) and in 44 patients in the 1995-1997 population [28.2%; mean
      difference: 36%; 95% confidence interval (ci): 31% to 40%; p < 0.0001]. Compared
      with 1995-1997, 2000-2002 was not significantly associated with an incremental
      dfs benefit for patients over a period of 7 years (2000-2002 vs. 1995-1997;
      adjusted hazard ratio: 0.98; 95% ci: 0.64 to 1.4). CONCLUSIONS: The treatment
      standard of adjuvant chemotherapy in addition to endocrine therapy may not be
      effective for all women with er/pr+ 1-3 ln+ esbc. There could be a subgroup of
      those women who do not benefit from adjuvant chemotherapy as expected and who are
      therefore being overtreated. Further studies with a larger sample size are
      warranted to confirm our results.

PMID- 23144581
TI  - Continuity clinics in oncology training programs in Canada.
AB  - PURPOSE: Continuity clinics (ccs) give trainees an opportunity for longitudinal
      follow-up of a patient cohort. Trainees can function in a semi-autonomous manner
      and prepare for independent practice. Data about such clinics in Canada are
      limited. Our objective was to assess the utility of ccs in Canadian oncology
      training programs. METHODS: Surveys were developed by the authors for medical and
      radiation oncology program directors (pds) and trainees, to assess the utility of
      ccs in Canadian oncology training programs.oncology patients, to assess their
      attitudes toward ccs. The pds were contacted by e-mail, using the Web site of the
      Canadian Resident Matching Service; the trainees were contacted by e-mail through
      the pds and their administrative assistants. Surveys were distributed
      electronically using SurveyMonkey. Patients were approached by staff oncologists
      during follow-up visits at The Ottawa Hospital Cancer Centre. RESULTS: Completed
      surveys were received from 33% of trainees and 63% of pds contacted; patient
      surveys were completed by 95 patients. Participation in a cc was reported by 47%
      of responding pds and 37% of responding trainees. Among respondents, 80% rated
      the ccs as "important" or "very important" to training. The biggest challenge
      identified by trainees and pds was lack of clinic space. Most pds (57%) and
      trainees (59%) felt that the staff oncologist should review the patient only if
      the trainee has concerns, but only 37% of patients shared that view (p = 0.0002).
      However, many patients expressed the desire to participate in trainee education.
      CONCLUSIONS: Continuity clinics are considered beneficial by pds and trainees.
      Patients desire more trainee supervision than the trainees themselves and the pds
      do, a factor that should be considered when implementing a cc.

PMID- 23144582
TI  - Mindfulness-based stress reduction for breast cancer-a systematic review and meta
      analysis.
AB  - OBJECTIVE: The aim of this systematic review and meta-analysis was to assess the
      effectiveness of mindfulness-based stress reduction (mbsr) and mindfulness-based
      cognitive therapy (mbct) in patients with breast cancer. METHODS: The medline,
      Cochrane Library, embase, cambase, and PsycInfo databases were screened through
      November 2011. The search strategy combined keywords for mbsr and mbct with
      keywords for breast cancer. Randomized controlled trials (rcts) comparing mbsr or
      mbct with control conditions in patients with breast cancer were included. Two
      authors independently used the Cochrane risk of bias tool to assess risk of bias
      in the selected studies. Study characteristics and outcomes were extracted by two
      authors independently. Primary outcome measures were health-related quality of
      life and psychological health. If at least two studies assessing an outcome were
      available, standardized mean differences (smds) and 95% confidence intervals
      (cis) were calculated for that outcome. As a measure of heterogeneity, I(2) was
      calculated. RESULTS: Three rcts with a total of 327 subjects were included. One
      rct compared mbsr with usual care, one rct compared mbsr with free-choice stress
      management, and a three-arm rct compared mbsr with usual care and with nutrition
      education. Compared with usual care, mbsr was superior in decreasing depression
      (smd: -0.37; 95% ci: -0.65 to -0.08; p = 0.01; I(2) = 0%) and anxiety (smd: 
      0.51; 95% ci: -0.80 to -0.21; p = 0.0009; I(2) = 0%), but not in increasing
      spirituality (smd: 0.27; 95% ci: -0.37 to 0.91; p = 0.41; I(2) = 79%).
      CONCLUSIONS: There is some evidence for the effectiveness of mbsr in improving
      psychological health in breast cancer patients, but more rcts are needed to
      underpin those results.

PMID- 23144583
TI  - Prognostic effect of early treatment of paraneoplastic limbic encephalitis in a
      patient with small-cell lung cancer.
AB  - Paraneoplastic neurologic syndrome (pns) is an uncommon manifestation of cancer
      and may present before any symptoms of malignant disease. This syndrome occurs in
      fewer than 1 of every 10,000 patients diagnosed with a malignancy. Anti-neural
      antibodies have been associated with pns, suggesting that this condition may
      reflect immune mechanisms. Depending on the region of the nervous system that has
      been affected, pns can have a number of manifestations. Paraneoplastic limbic
      encephalitis (ple) stems from involvement of the limbic system and may present
      with seizures and changes in mood, memory, and personality. The present report
      describes the case of a 55-year-old man presenting with ple in the setting of
      small-cell lung cancer, with subsequent improvement of his neurologic symptoms.
      The value of rapid diagnosis and multidisciplinary management of this syndrome
      are discussed.

PMID- 23144584
TI  - Adenocarcinoma not otherwise specified on dorsum of tongue: case report and
      literature review.
AB  - Primary adenocarcinoma of the oropharynx most often arises from the minor
      salivary glands, and primary squamous cell carcinoma is more commonly seen
      arising from the tongue. Few cases of adenocarcinoma not otherwise specified of
      the tongue have been reported in the literature, and none found on the dorsum of
      the tongue. Successful treatment strategies have therefore not been defined.We
      report a case of adenocarcinoma located on the dorsum of the posterior one third
      of the tongue adjacent to the circumvallate papillae in a woman presenting with
      globus sensation and mild dysphagia. Treatment consisted of transoral laser
      excision and postoperative external-beam radiotherapy, resulting in disease-free
      survival at her 5-year follow-up. The goals of this report are to present a case
      of adenocarcinoma arising from the minor salivary gland located on the dorsum of
      the tongue, to discuss previous reports of similar cases, and to suggest that
      surgery with or without radiotherapy be used as the mainstay of treatment.

PMID- 23144585
TI  - Politics, health, and mesothelioma: when it comes to cancer, none is one too
      many.

PMID- 23144586
TI  - Mobile monitoring of particle number concentration and other traffic-related air
      pollutants in a near-highway neighborhood over the course of a year.
AB  - Accurate quantification of exposures to traffic-related air pollution in near
      highway neighborhoods is challenging due to the high degree of spatial and
      temporal variation of pollutant levels. The objective of this study was to
      measure air pollutant levels in a near-highway urban area over a wide range of
      traffic and meteorological conditions using a mobile monitoring platform. The
      study was performed in a 2.3-km(2) area in Somerville, Massachusetts (USA), near
      Interstate I-93, a highway that carries 150,000 vehicles per day. The mobile
      platform was equipped with rapid-response instruments and was driven repeatedly
      along a 15.4-km route on 55 days between September 2009 and August 2010.
      Monitoring was performed in 4-6-hour shifts in the morning, afternoon and evening
      on both weekdays and weekends in winter, spring, summer and fall. Measurements
      were made of particle number concentration (PNC; 4-3,000 nm), particle size
      distribution, fine particle mass (PM(2.5)), particle-bound polycyclic aromatic
      hydrocarbons (pPAH), black carbon (BC), carbon monoxide (CO), and nitrogen oxides
      (NO and NO(x)). The highest pollutant concentrations were measured within 0-50 m
      of I-93 with distance-decay gradients varying depending on traffic and
      meteorology. The most pronounced variations were observed for PNC. Annual median
      PNC 0-50 m from I-93 was two-fold higher compared to the background area (>1 km
      from I-93). In general, PNC levels were highest in winter and lowest in summer
      and fall, higher on weekdays and Saturdays compared to Sundays, and higher during
      morning rush hour compared to later in the day. Similar spatial and temporal
      trends were observed for NO, CO and BC, but not for PM(2.5). Spatial variations
      in PNC distance-decay gradients were non-uniform largely due to contributions
      from local street traffic. Hour-to-hour, day-to-day and season-to-season
      variations in PNC were of the same magnitude as spatial variations. Datasets
      containing fine-scale temporal and spatial variation of air pollution levels near
      highways may help to inform exposure assessment efforts.

PMID- 23144587
TI  - Spatially varying predictors of teenage birth rates among counties in the United
      States.
AB  - BACKGROUND: Limited information is available about teenage pregnancy and
      childbearing in rural areas, even though approximately 20 percent of the nation's
      youth live in rural areas. Identifying whether there are differences in the
      teenage birth rate (TBR) across metropolitan and nonmetropolitan areas is
      important, because these differences may reflect modifiable ecological-level
      influences such as education, employment, laws, healthcare infrastructure, and
      policies that could potentially reduce the TBR.  OBJECTIVES: The goals of this
      study are to investigate whether there are spatially varying relationships
      between the TBR and the independent variables, and if so, whether these
      associations differ between metropolitan and nonmetropolitan counties.  METHODS:
      We explore the heterogeneity within metropolitan/nonmetropolitan county groups
      separately using geographically weighted regression (GWR), and investigate the
      difference between metropolitan/nonmetropolitan counties using spatial regime
      models with spatial errors. These analyses were applied to county-level data from
      the National Center for Health Statistics and the US Census Bureau.  RESULTS: GWR
      results suggested that non-stationarity exists in the associations between TBR
      and determinants within metropolitan/nonmetropolitan groups. The spatial regime
      analysis indicated that the effect of socioeconomic disadvantage on TBR
      significantly varied by the metropolitan status of counties.  CONCLUSIONS: While
      the spatially varying relationships between the TBR and independent variables
      were found within each metropolitan status of counties, only the magnitude of the
      impact of the socioeconomic disadvantage index is significantly stronger among
      metropolitan counties than nonmetropolitan counties. Our findings suggested that
      place-specific policies for the disadvantaged groups in a county could be
      implemented to reduce TBR in the US.

PMID- 23144588
TI  - Growth of oriented p-aminobenzoic acid crystals by directional freezing.
AB  - Oriented long needle-like p-aminobenzoic acid (PABA) crystals are successfully
      prepared by directional freezing of PABA solution in this work. The width of the
      oriented crystals is controlled by changing the directional cooling rate,
      resulting in varying crystal morphologies and thermodynamic properties while
      maintaining the same chemical structure.

PMID- 23144590
TI  - Delineating West Nile Virus Transmission Cycles at Various Scales: The Nearest
      Neighbor Distance-Time Model.
AB  - Various approaches are used to identify West Nile virus (WNV) exposure areas,
      including unusual sightings of infected dead birds, mosquito pools or human cases
      both prospectively and retrospectively. A significant and largely unmet need in
      WNV research is to incorporate the temporal characterization of virus spread and
      locational information of the three components of transmission cycle-i.e., birds
      (reservoir), mosquitoes (vector), and humans (host)-on a localized scale.
      Exposure areas containing all three components of the WNV cycle in close
      proximity have higher potential to amplify an outbreak as compared to exposure
      areas delineated by a single component. In this paper, we introduce a novel
      approach, termed 'Nearest Neighbor Distance Time' or NNDT, to identify and
      retrospectively monitor WNV transmission cycles on various scales in the Twin
      Cities Metropolitan area of Minnesota. The NNDT model was implemented in a
      geographic information system using data from the period 2002 to 2006. The
      results indicated that 2002 and 2003 had three such WNV cycles, followed by one,
      two, and four respectively in 2004, 2005, and 2006. The NNDT method can be useful
      in locating chronically exposed areas and generating hypotheses about the
      transmission of WNV.

PMID- 23144591
TI  - Effects of Web-Mediated Teacher Professional Development on the Language and
      Literacy Skills of Children Enrolled in Pre-Kindergarten Programs.
AB  - As early education grows in the United States, in-service professional
      development in key instructional and interaction skills is a core component of
      capacity-building in early childhood education. In this paper, we describe
      results from an evaluation of the effects of MyTeachingPartner, a web-based
      system of professional development, on language and literacy development during
      pre-kindergarten for 1338 children in 161 teachers' classrooms. High levels of
      support for teachers' implementation of language/literacy activities showed
      modest but significant effects for improving early language and literacy for
      children in classrooms in which English was the dominant language spoken by the
      students and teachers. The combination of web-based supports, including video
      based consultation and web-based video teaching exemplars, was more effective at
      improving children's literacy and language skills than was only making available
      to teachers a set of instructional materials and detailed lesson guides. These
      results suggest the importance of targeted, practice-focused supports for
      teachers in designing professional development systems for effective teaching in
      early childhood programs.

PMID- 23144589
TI  - A Critical Kinase Cascade in Neurological Disorders: PI 3-K, Akt, and mTOR.
AB  - Neurodegenerative disorders lead to disability and death in a significant
      proportion of the world's population. However, many disorders of the nervous
      system remain with limited effective treatments. Kinase pathways in the nervous
      system that involve phosphoinositide 3-kinase (PI 3-K), protein kinase B (Akt),
      and the mammalian target of rapamycin (mTOR) offer exciting prospects for the
      understanding of neurodegenerative pathways and the development of new avenues of
      treatment. PI 3-K, Akt, and mTOR pathways are vital cellular components that
      determine cell fate during acute and chronic disorders, such as Huntington's
      disease, Alzheimer's disease, Parkinson's disease, epilepsy, stroke, and trauma.
      Yet, the elaborate relationship among these kinases and the variable control of
      apoptosis and autophagy can lead to unanticipated biological and clinical
      outcomes. Crucial for the successful translation of PI 3-K, Akt, and mTOR into
      robust and safe clinical strategies will be the further elucidation of the
      complex roles that these kinase pathways hold in the nervous system.

PMID- 23144592
TI  - Using EEG to Study Cognitive Development: Issues and Practices.
AB  - Developmental research is enhanced by use of multiple methodologies for examining
      psychological processes. The electroencephalogram (EEG) is an efficient and
      relatively inexpensive method for the study of developmental changes in brain
      behavior relations. In this review, we highlight some of the challenges for using
      EEG in cognitive development research. We also list best practices for
      incorporating this methodology into the study of early cognitive processes.
      Consideration of these issues is critical for making an informed decision
      regarding implementation of EEG methodology.

PMID- 23144593
TI  - Metal-Assisted and Microwave-Accelerated Evaporative Crystallization: Application
      to L-Alanine.
AB  - L-Alanine is an important amino acid that plays a key role in the molecular
      structure of many proteins. Crystallized forms of this molecule are currently in
      high demand in chemical, pharmaceutics, and food industries. However, the
      traditional evaporative crystallization method takes up to several hours to
      complete and does not always consistently yield usable crystals. Using the metal
      assisted and microwave-accelerated evaporative crystallization (MA-MAEC)
      technique, larger and better-organized L-alanine crystals were formed in a
      fraction of the time using room temperature crystallization. This technique may
      be applicable to organic molecules other than amino acids and thus will be able
      to produce the large amount of molecular crystals desired by industries today.

PMID- 23144594
TI  - Parenting as Phenotype: A Behavioral Genetic Approach to Understanding Parenting.
AB  - This article discusses the behavioral genetic (BG) approach to parenting.
      Parenting is considered a phenotype that can be influenced by nature and nurture.
      Genetic contributions to parenting are conceptualized as evidence of genotype
      environment correlation (rGE). Early BG studies focused on demonstrating that
      some parenting dimensions were heritable due to passive and evocative rGE
      processes. Current studies are investigating moderators and mediators of genetic
      and environmental contributions to parenting. The paper uses parent and child
      report data on parental warmth from the Twins, Adoptees, Peers, and Siblings
      (TAPS) study to illustrate the BG approach. Results show that heritability is
      significant for parent and child reports, but environmental influences differ by
      information source. Three questions are addressed concerning the BG approach to
      parenting: What is the nature of parenting? How does the approach inform
      parenting practice and interventions? What are the future directions?

PMID- 23144595
TI  - NEW FATHER'S EXPERIENCES WITH THEIR OWN FATHERS AND ATTITUDES TOWARD FATHERING.
AB  - Using the baseline father sample of the Fragile Families and Child Wellbeing
      Survey (n=3,525), I consider how father type and presence and biological father
      involvement is associated with new father's attitudes toward fathering, testing
      the modeling and compensatory hypotheses. Results generally support the modeling
      hypothesis. Relative to new fathers who had a very involved coresidential father,
      men whose father was less involved are less likely to support the notion that
      fathers serve as authority figures. Men who had neither a coresidential father
      nor a father figure and whose biological father was not very involved are less
      agreeable to the idea that fathers are important sources of financial support or
      direct care. Weak support for the compensatory hypothesis is found for more
      global attitudes toward fatherhood and in results suggesting men with a father
      figure have more favorable father attitudes than men who did not have a father
      figure.

PMID- 23144596
TI  - Stereoscopy and the Human Visual System.
AB  - Stereoscopic displays have become important for many applications, including
      operation of remote devices, medical imaging, surgery, scientific visualization,
      and computer-assisted design. But the most significant and exciting development
      is the incorporation of stereo technology into entertainment: specifically,
      cinema, television, and video games. In these applications for stereo, three
      dimensional (3D) imagery should create a faithful impression of the 3D structure
      of the scene being portrayed. In addition, the viewer should be comfortable and
      not leave the experience with eye fatigue or a headache. Finally, the
      presentation of the stereo images should not create temporal artifacts like
      flicker or motion judder. This paper reviews current research on stereo human
      vision and how it informs us about how best to create and present stereo 3D
      imagery. The paper is divided into four parts: (1) getting the geometry right,
      (2) depth cue interactions in stereo 3D media, (3) focusing and fixating on
      stereo images, and (4) how temporal presentation protocols affect flicker, motion
      artifacts, and depth distortion.

PMID- 23144597
TI  - Differential Flap Dynamics in Wild-type and a Drug Resistant Variant of HIV-1
      Protease Revealed by Molecular Dynamics and NMR Relaxation.
AB  - In the rapidly evolving disease of HIV drug resistance readily emerges,
      nullifying the effectiveness of therapy. Drug resistance has been extensively
      studied in HIV-1 protease where resistance occurs when the balance between enzyme
      inhibition and substrate recognition and turn-over is perturbed to favor
      catalytic activity. Mutations which confer drug resistance can impact the
      dynamics and structure of both the bound and unbound forms of the enzyme. Flap+
      is a multi-drug-resistant variant of HIV-1 protease with a combination of
      mutations at the edge of the active site, within the active site, and in the
      flaps (L10I, G48V, I54V, V82A). The impact of these mutations on the dynamics in
      the unliganded form in comparison with the wild-type protease was elucidated with
      Molecular Dynamic simulations and NMR relaxation experiments. The comparative
      analyses from both methods concur in showing that the enzyme's dynamics are
      impacted by the drug resistance mutations in Flap+ protease. These alterations in
      the enzyme dynamics, particularly within the flaps, likely modulate the balance
      between substrate turn-over and drug binding, thereby conferring drug resistance.

PMID- 23144598
TI  - Site-Specific Fragment Identification Guided by Single-Step Free Energy
      Perturbation Calculations.
AB  - The in-silico Site Identification by Ligand Competitive Saturation (SILCS)
      approach identifies the binding sites of representative chemical entities on the
      entire protein surface, information that can be applied for computational
      fragment-based drug design. In this study, we report an efficient computational
      protocol that uses sampling of the protein-fragment conformational space obtained
      from the SILCS simulations and performs single step free energy perturbation
      (SSFEP) calculations to identify site-specific favorable chemical modifications
      of benzene involving substitutions of ring hydrogens with individual non-hydrogen
      atoms. The SSFEP method is able to capture the experimental trends in relative
      hydration free energies of benzene analogues and for two datasets of experimental
      relative binding free energies of congeneric series of ligands of the proteins
      alpha-thrombin and P38 MAP kinase. The approach includes a protocol in which data
      obtained from SILCS simulations of the proteins is first analyzed to identify
      favorable benzene binding sites following which an ensemble of benzene-protein
      conformations for that site is obtained. The SSFEP protocol applied to that
      ensemble results in good reproduction of experimental free energies of the alpha
      thrombin ligands, but not for P38 MAP kinase ligands. Comparison with results
      from a P38 full-ligand simulation and analysis of conformations reveals the
      reason for the poor agreement being the connectivity with the remainder of the
      ligand, a limitation inherent in fragment-based methods. Since the SSFEP approach
      can identify favorable benzene modifications as well as identify the most
      favorable fragment conformations, the obtained information can be of value for
      fragment linking or structure-based optimization.

PMID- 23144599
TI  - Coordinated optimization of visual cortical maps (I) symmetry-based analysis.
AB  - In the primary visual cortex of primates and carnivores, functional architecture
      can be characterized by maps of various stimulus features such as orientation
      preference (OP), ocular dominance (OD), and spatial frequency. It is a long
      standing question in theoretical neuroscience whether the observed maps should be
      interpreted as optima of a specific energy functional that summarizes the design
      principles of cortical functional architecture. A rigorous evaluation of this
      optimization hypothesis is particularly demanded by recent evidence that the
      functional architecture of orientation columns precisely follows species
      invariant quantitative laws. Because it would be desirable to infer the form of
      such an optimization principle from the biological data, the optimization
      approach to explain cortical functional architecture raises the following
      questions: i) What are the genuine ground states of candidate energy functionals
      and how can they be calculated with precision and rigor? ii) How do differences
      in candidate optimization principles impact on the predicted map structure and
      conversely what can be learned about a hypothetical underlying optimization
      principle from observations on map structure? iii) Is there a way to analyze the
      coordinated organization of cortical maps predicted by optimization principles in
      general? To answer these questions we developed a general dynamical systems
      approach to the combined optimization of visual cortical maps of OP and another
      scalar feature such as OD or spatial frequency preference. From basic symmetry
      assumptions we obtain a comprehensive phenomenological classification of possible
      inter-map coupling energies and examine representative examples. We show that
      each individual coupling energy leads to a different class of OP solutions with
      different correlations among the maps such that inferences about the optimization
      principle from map layout appear viable. We systematically assess whether
      quantitative laws resembling experimental observations can result from the
      coordinated optimization of orientation columns with other feature maps.

PMID- 23144600
TI  - A graphical modelling approach to the dissection of highly correlated
      transcription factor binding site profiles.
AB  - Inferring the combinatorial regulatory code of transcription factors (TFs) from
      genome-wide TF binding profiles is challenging. A major reason is that TF binding
      profiles significantly overlap and are therefore highly correlated. Clustered
      occurrence of multiple TFs at genomic sites may arise from chromatin
      accessibility and local cooperation between TFs, or binding sites may simply
      appear clustered if the profiles are generated from diverse cell populations.
      Overlaps in TF binding profiles may also result from measurements taken at
      closely related time intervals. It is thus of great interest to distinguish TFs
      that directly regulate gene expression from those that are indirectly associated
      with gene expression. Graphical models, in particular Bayesian networks, provide
      a powerful mathematical framework to infer different types of dependencies.
      However, existing methods do not perform well when the features (here: TF binding
      profiles) are highly correlated, when their association with the biological
      outcome is weak, and when the sample size is small. Here, we develop a novel
      computational method, the Neighbourhood Consistent PC (NCPC) algorithms, which
      deal with these scenarios much more effectively than existing methods do. We
      further present a novel graphical representation, the Direct Dependence Graph
      (DDGraph), to better display the complex interactions among variables. NCPC and
      DDGraph can also be applied to other problems involving highly correlated
      biological features. Both methods are implemented in the R package ddgraph,
      available as part of Bioconductor
      (http://bioconductor.org/packages/2.11/bioc/html/ddgraph.html). Applied to real
      data, our method identified TFs that specify different classes of cis-regulatory
      modules (CRMs) in Drosophila mesoderm differentiation. Our analysis also found
      depletion of the early transcription factor Twist binding at the CRMs regulating
      expression in visceral and somatic muscle cells at later stages, which suggests a
      CRM-specific repression mechanism that so far has not been characterised for this
      class of mesodermal CRMs.

PMID- 23144601
TI  - Functional inference of complex anatomical tendinous networks at a macroscopic
      scale via sparse experimentation.
AB  - In systems and computational biology, much effort is devoted to functional
      identification of systems and networks at the molecular-or cellular scale.
      However, similarly important networks exist at anatomical scales such as the
      tendon network of human fingers: the complex array of collagen fibers that
      transmits and distributes muscle forces to finger joints. This network is
      critical to the versatility of the human hand, and its function has been debated
      since at least the 16(th) century. Here, we experimentally infer the structure
      (both topology and parameter values) of this network through sparse interrogation
      with force inputs. A population of models representing this structure co-evolves
      in simulation with a population of informative future force inputs via the
      predator-prey estimation-exploration algorithm. Model fitness depends on their
      ability to explain experimental data, while the fitness of future force inputs
      depends on causing maximal functional discrepancy among current models. We
      validate our approach by inferring two known synthetic Latex networks, and one
      anatomical tendon network harvested from a cadaver's middle finger. We find that
      functionally similar but structurally diverse models can exist within a narrow
      range of the training set and cross-validation errors. For the Latex networks,
      models with low training set error [<4%] and resembling the known network have
      the smallest cross-validation errors [~5%]. The low training set [<4%] and cross
      validation [<7.2%] errors for models for the cadaveric specimen demonstrate what,
      to our knowledge, is the first experimental inference of the functional structure
      of complex anatomical networks. This work expands current bioinformatics
      inference approaches by demonstrating that sparse, yet informative interrogation
      of biological specimens holds significant computational advantages in accurate
      and efficient inference over random testing, or assuming model topology and only
      inferring parameters values. These findings also hold clues to both our
      evolutionary history and the development of versatile machines.

PMID- 23144603
TI  - Efficient "communication through coherence" requires oscillations structured to
      minimize interference between signals.
AB  - The 'communication through coherence' (CTC) hypothesis proposes that selective
      communication among neural networks is achieved by coherence between firing rate
      oscillation in a sending region and gain modulation in a receiving region.
      Although this hypothesis has stimulated extensive work, it remains unclear
      whether the mechanism can in principle allow reliable and selective information
      transfer. Here we use a simple mathematical model to investigate how accurately
      coherent gain modulation can filter a population-coded target signal from task
      irrelevant distracting inputs. We show that selective communication can indeed be
      achieved, although the structure of oscillatory activity in the target and
      distracting networks must satisfy certain previously unrecognized constraints.
      Firstly, the target input must be differentiated from distractors by the
      amplitude, phase or frequency of its oscillatory modulation. When distracting
      inputs oscillate incoherently in the same frequency band as the target,
      communication accuracy is severely degraded because of varying overlap between
      the firing rate oscillations of distracting inputs and the gain modulation in the
      receiving region. Secondly, the oscillatory modulation of the target input must
      be strong in order to achieve a high signal-to-noise ratio relative to stochastic
      spiking of individual neurons. Thus, whilst providing a quantitative
      demonstration of the power of coherent oscillatory gain modulation to flexibly
      control information flow, our results identify constraints imposed by the need to
      avoid interference between signals, and reveal a likely organizing principle for
      the structure of neural oscillations in the brain.

PMID- 23144604
TI  - Ten simple rules to protect your intellectual property.

PMID- 23144602
TI  - Coordinated optimization of visual cortical maps (II) numerical studies.
AB  - In the juvenile brain, the synaptic architecture of the visual cortex remains in
      a state of flux for months after the natural onset of vision and the initial
      emergence of feature selectivity in visual cortical neurons. It is an attractive
      hypothesis that visual cortical architecture is shaped during this extended
      period of juvenile plasticity by the coordinated optimization of multiple visual
      cortical maps such as orientation preference (OP), ocular dominance (OD), spatial
      frequency, or direction preference. In part (I) of this study we introduced a
      class of analytically tractable coordinated optimization models and solved
      representative examples, in which a spatially complex organization of the OP map
      is induced by interactions between the maps. We found that these solutions near
      symmetry breaking threshold predict a highly ordered map layout. Here we examine
      the time course of the convergence towards attractor states and optima of these
      models. In particular, we determine the timescales on which map optimization
      takes place and how these timescales can be compared to those of visual cortical
      development and plasticity. We also assess whether our models exhibit
      biologically more realistic, spatially irregular solutions at a finite distance
      from threshold, when the spatial periodicities of the two maps are detuned and
      when considering more than 2 feature dimensions. We show that, although maps
      typically undergo substantial rearrangement, no other solutions than pinwheel
      crystals and stripes dominate in the emerging layouts. Pinwheel crystallization
      takes place on a rather short timescale and can also occur for detuned
      wavelengths of different maps. Our numerical results thus support the view that
      neither minimal energy states nor intermediate transient states of our
      coordinated optimization models successfully explain the architecture of the
      visual cortex. We discuss several alternative scenarios that may improve the
      agreement between model solutions and biological observations.

PMID- 23144605
TI  - Functional analysis of metabolic channeling and regulation in lignin
      biosynthesis: a computational approach.
AB  - Lignin is a polymer in secondary cell walls of plants that is known to have
      negative impacts on forage digestibility, pulping efficiency, and sugar release
      from cellulosic biomass. While targeted modifications of different lignin
      biosynthetic enzymes have permitted the generation of transgenic plants with
      desirable traits, such as improved digestibility or reduced recalcitrance to
      saccharification, some of the engineered plants exhibit monomer compositions that
      are clearly at odds with the expected outcomes when the biosynthetic pathway is
      perturbed. In Medicago, such discrepancies were partly reconciled by the recent
      finding that certain biosynthetic enzymes may be spatially organized into two
      independent channels for the synthesis of guaiacyl (G) and syringyl (S) lignin
      monomers. Nevertheless, the mechanistic details, as well as the biological
      function of these interactions, remain unclear. To decipher the working
      principles of this and similar control mechanisms, we propose and employ here a
      novel computational approach that permits an expedient and exhaustive assessment
      of hundreds of minimal designs that could arise in vivo. Interestingly, this
      comparative analysis not only helps distinguish two most parsimonious mechanisms
      of crosstalk between the two channels by formulating a targeted and readily
      testable hypothesis, but also suggests that the G lignin-specific channel is more
      important for proper functioning than the S lignin-specific channel. While the
      proposed strategy of analysis in this article is tightly focused on lignin
      synthesis, it is likely to be of similar utility in extracting unbiased
      information in a variety of situations, where the spatial organization of
      molecular components is critical for coordinating the flow of cellular
      information, and where initially various control designs seem equally valid.

PMID- 23144606
TI  - Stochastic modeling of expression kinetics identifies messenger half-lives and
      reveals sequential waves of co-ordinated transcription and decay.
AB  - The transcriptome in a cell is finely regulated by a large number of molecular
      mechanisms able to control the balance between mRNA production and degradation.
      Recent experimental findings have evidenced that fine and specific regulation of
      degradation is needed for proper orchestration of a global cell response to
      environmental conditions. We developed a computational technique based on
      stochastic modeling, to infer condition-specific individual mRNA half-lives
      directly from gene expression time-courses. Predictions from our method were
      validated by experimentally measured mRNA decay rates during the
      intraerythrocytic developmental cycle of Plasmodium falciparum. We then applied
      our methodology to publicly available data on the reproductive and metabolic
      cycle of budding yeast. Strikingly, our analysis revealed, in all cases, the
      presence of periodic changes in decay rates of sequentially induced genes and co
      ordination strategies between transcription and degradation, thus suggesting a
      general principle for the proper coordination of transcription and degradation
      machinery in response to internal and/or external stimuli.

PMID- 23144607
TI  - Distinct neurogenomic states in basal ganglia subregions relate differently to
      singing behavior in songbirds.
AB  - Both avian and mammalian basal ganglia are involved in voluntary motor control.
      In birds, such movements include hopping, perching and flying. Two organizational
      features that distinguish the songbird basal ganglia are that striatal and
      pallidal neurons are intermingled, and that neurons dedicated to vocal-motor
      function are clustered together in a dense cell group known as area X that sits
      within the surrounding striato-pallidum. This specification allowed us to perform
      molecular profiling of two striato-pallidal subregions, comparing transcriptional
      patterns in tissue dedicated to vocal-motor function (area X) to those in tissue
      that contains similar cell types but supports non-vocal behaviors: the striato
      pallidum ventral to area X (VSP), our focus here. Since any behavior is likely
      underpinned by the coordinated actions of many molecules, we constructed gene co
      expression networks from microarray data to study large-scale transcriptional
      patterns in both subregions. Our goal was to investigate any relationship between
      VSP network structure and singing and identify gene co-expression groups, or
      modules, found in the VSP but not area X. We observed mild, but surprising,
      relationships between VSP modules and song spectral features, and found a group
      of four VSP modules that were highly specific to the region. These modules were
      unrelated to singing, but were composed of genes involved in many of the same
      biological processes as those we previously observed in area X-specific singing
      related modules. The VSP-specific modules were also enriched for processes
      disrupted in Parkinson's and Huntington's Diseases. Our results suggest that the
      activation/inhibition of a single pathway is not sufficient to functionally
      specify area X versus the VSP and support the notion that molecular processes are
      not in and of themselves specialized for behavior. Instead, unique interactions
      between molecular pathways create functional specificity in particular brain
      regions during distinct behavioral states.

PMID- 23144608
TI  - Phenoloxidase activity acts as a mosquito innate immune response against
      infection with Semliki Forest virus.
AB  - Several components of the mosquito immune system including the RNA interference
      (RNAi), JAK/STAT, Toll and IMD pathways have previously been implicated in
      controlling arbovirus infections. In contrast, the role of the phenoloxidase (PO)
      cascade in mosquito antiviral immunity is unknown. Here we show that conditioned
      medium from the Aedes albopictus-derived U4.4 cell line contains a functional PO
      cascade, which is activated by the bacterium Escherichia coli and the arbovirus
      Semliki Forest virus (SFV) (Togaviridae; Alphavirus). Production of recombinant
      SFV expressing the PO cascade inhibitor Egf1.0 blocked PO activity in U4.4 cell-
      conditioned medium, which resulted in enhanced spread of SFV. Infection of adult
      female Aedes aegypti by feeding mosquitoes a bloodmeal containing Egf1.0
      expressing SFV increased virus replication and mosquito mortality. Collectively,
      these results suggest the PO cascade of mosquitoes plays an important role in
      immune defence against arboviruses.

PMID- 23144609
TI  - Tim-3-expressing CD4+ and CD8+ T cells in human tuberculosis (TB) exhibit
      polarized effector memory phenotypes and stronger anti-TB effector functions.
AB  - T-cell immune responses modulated by T-cell immunoglobulin and mucin domain
      containing molecule 3 (Tim-3) during Mycobacterium tuberculosis (Mtb) infection
      in humans remain poorly understood. Here, we found that active TB patients
      exhibited increases in numbers of Tim-3-expressing CD4(+) and CD8(+) T cells,
      which preferentially displayed polarized effector memory phenotypes. Consistent
      with effector phenotypes, Tim-3(+)CD4(+) and Tim-3(+)CD8(+) T-cell subsets showed
      greater effector functions for producing Th1/Th22 cytokines and CTL effector
      molecules than Tim-3(-) counterparts, and Tim-3-expressing T cells more
      apparently limited intracellular Mtb replication in macrophages. The increased
      effector functions for Tim-3-expressing T cells consisted with cellular
      activation signaling as Tim-3(+)CD4(+) and Tim-3(+)CD8(+) T-cell subsets
      expressed much higher levels of phosphorylated signaling molecules p38, stat3,
      stat5, and Erk1/2 than Tim-3- controls. Mechanistic experiments showed that siRNA
      silencing of Tim-3 or soluble Tim-3 treatment interfering with membrane Tim-3
      ligand interaction reduced de novo production of IFN-gamma and TNF-alpha by Tim-3
      expressing T cells. Furthermore, stimulation of Tim-3 signaling pathways by
      antibody cross-linking of membrane Tim-3 augmented effector function of IFN-gamma
      production by CD4(+) and CD8(+) T cells, suggesting that Tim-3 signaling helped
      to drive stronger effector functions in active TB patients. This study therefore
      uncovered a previously unknown mechanism for T-cell immune responses regulated by
      Tim-3, and findings may have implications for potential immune intervention in
      TB.

PMID- 23144610
TI  - Distinct effects on diversifying selection by two mechanisms of immunity against
      Streptococcus pneumoniae.
AB  - Antigenic variation to evade host immunity has long been assumed to be a driving
      force of diversifying selection in pathogens. Colonization by Streptococcus
      pneumoniae, which is central to the organism's transmission and therefore
      evolution, is limited by two arms of the immune system: antibody- and T cell-
      mediated immunity. In particular, the effector activity of CD4(+) T(H)17 cell
      mediated immunity has been shown to act in trans, clearing co-colonizing
      pneumococci that do not bear the relevant antigen. It is thus unclear whether
      T(H)17 cell immunity allows benefit of antigenic variation and contributes to
      diversifying selection. Here we show that antigen-specific CD4(+) T(H)17 cell
      immunity almost equally reduces colonization by both an antigen-positive strain
      and a co-colonized, antigen-negative strain in a mouse model of pneumococcal
      carriage, thus potentially minimizing the advantage of escape from this type of
      immunity. Using a proteomic screening approach, we identified a list of candidate
      human CD4(+) T(H)17 cell antigens. Using this list and a previously published
      list of pneumococcal Antibody antigens, we bioinformatically assessed the signals
      of diversifying selection among the identified antigens compared to non-antigens.
      We found that Antibody antigen genes were significantly more likely to be under
      diversifying selection than the T(H)17 cell antigen genes, which were
      indistinguishable from non-antigens. Within the Antibody antigens, epitopes
      recognized by human antibodies showed stronger evidence of diversifying
      selection. Taken together, the data suggest that T(H)17 cell-mediated immunity,
      one form of T cell immunity that is important to limit carriage of antigen
      positive pneumococcus, favors little diversifying selection in the targeted
      antigen. The results could provide new insight into pneumococcal vaccine design.

PMID- 23144611
TI  - Enhancing blockade of Plasmodium falciparum erythrocyte invasion: assessing
      combinations of antibodies against PfRH5 and other merozoite antigens.
AB  - No vaccine has yet proven effective against the blood-stages of Plasmodium
      falciparum, which cause the symptoms and severe manifestations of malaria. We
      recently found that PfRH5, a P. falciparum-specific protein expressed in
      merozoites, is efficiently targeted by broadly-neutralizing, vaccine-induced
      antibodies. Here we show that antibodies against PfRH5 efficiently inhibit the in
      vitro growth of short-term-adapted parasite isolates from Cambodia, and that the
      EC(50) values of antigen-specific antibodies against PfRH5 are lower than those
      against PfAMA1. Since antibody responses elicited by multiple antigens are
      speculated to improve the efficacy of blood-stage vaccines, we conducted detailed
      assessments of parasite growth inhibition by antibodies against PfRH5 in
      combination with antibodies against seven other merozoite antigens. We found that
      antibodies against PfRH5 act synergistically with antibodies against certain
      other merozoite antigens, most notably with antibodies against other erythrocyte
      binding antigens such as PfRH4, to inhibit the growth of a homologous P.
      falciparum clone. A combination of antibodies against PfRH4 and basigin, the
      erythrocyte receptor for PfRH5, also potently inhibited parasite growth. This
      methodology provides the first quantitative evidence that polyclonal vaccine
      induced antibodies can act synergistically against P. falciparum antigens and
      should help to guide the rational development of future multi-antigen vaccines.

PMID- 23144612
TI  - The polymorphic pseudokinase ROP5 controls virulence in Toxoplasma gondii by
      regulating the active kinase ROP18.
AB  - Secretory polymorphic serine/threonine kinases control pathogenesis of Toxoplasma
      gondii in the mouse. Genetic studies show that the pseudokinase ROP5 is essential
      for acute virulence, but do not reveal its mechanism of action. Here we
      demonstrate that ROP5 controls virulence by blocking IFN-gamma mediated clearance
      in activated macrophages. ROP5 was required for the catalytic activity of the
      active S/T kinase ROP18, which phosphorylates host immunity related GTPases
      (IRGs) and protects the parasite from clearance. ROP5 directly regulated activity
      of ROP18 in vitro, and both proteins were necessary to avoid IRG recruitment and
      clearance in macrophages. Clearance of both the Deltarop5 and Deltarop18 mutants
      was reversed in macrophages lacking Irgm3, which is required for IRG function,
      and the virulence defect was fully restored in Irgm3(-/-) mice. Our findings
      establish that the pseudokinase ROP5 controls the activity of ROP18, thereby
      blocking IRG mediated clearance in macrophages. Additionally, ROP5 has other
      functions that are also Irgm3 and IFN-gamma dependent, indicting it plays a
      general role in governing virulence factors that block immunity.

PMID- 23144614
TI  - A wolf in sheep's clothing: SV40 co-opts host genome maintenance proteins to
      replicate viral DNA.

PMID- 23144613
TI  - Mapping the phosphoproteome of influenza A and B viruses by mass spectrometry.
AB  - Protein phosphorylation is a common post-translational modification in eukaryotic
      cells and has a wide range of functional effects. Here, we used mass spectrometry
      to search for phosphorylated residues in all the proteins of influenza A and B
      viruses--to the best of our knowledge, the first time such a comprehensive
      approach has been applied to a virus. We identified 36 novel phosphorylation
      sites, as well as confirming 3 previously-identified sites. N-terminal processing
      and ubiquitination of viral proteins was also detected. Phosphorylation was
      detected in the polymerase proteins (PB2, PB1 and PA), glycoproteins (HA and NA),
      nucleoprotein (NP), matrix protein (M1), ion channel (M2), non-structural protein
      (NS1) and nuclear export protein (NEP). Many of the phosphorylation sites
      detected were conserved between influenza virus genera, indicating the
      fundamental importance of phosphorylation for all influenza viruses. Their
      structural context indicates roles for phosphorylation in regulating viral entry
      and exit (HA and NA); nuclear localisation (PB2, M1, NP, NS1 and, through NP and
      NEP, of the viral RNA genome); and protein multimerisation (NS1 dimers, M2
      tetramers and NP oligomers). Using reverse genetics we show that for NP of
      influenza A viruses phosphorylation sites in the N-terminal NLS are important for
      viral growth, whereas mutating sites in the C-terminus has little or no effect.
      Mutating phosphorylation sites in the oligomerisation domains of NP inhibits
      viral growth and in some cases transcription and replication of the viral RNA
      genome. However, constitutive phosphorylation of these sites is not optimal.
      Taken together, the conservation, structural context and functional significance
      of phosphorylation sites implies a key role for phosphorylation in influenza
      biology. By identifying phosphorylation sites throughout the proteomes of
      influenza A and B viruses we provide a framework for further study of
      phosphorylation events in the viral life cycle and suggest a range of potential
      antiviral targets.

PMID- 23144615
TI  - Structural and functional insights into the HIV-1 maturation inhibitor binding
      pocket.
AB  - Processing of the Gag precursor protein by the viral protease during particle
      release triggers virion maturation, an essential step in the virus replication
      cycle. The first-in-class HIV-1 maturation inhibitor dimethylsuccinyl betulinic
      acid [PA-457 or bevirimat (BVM)] blocks HIV-1 maturation by inhibiting the
      cleavage of the capsid-spacer peptide 1 (CA-SP1) intermediate to mature CA. A
      structurally distinct molecule, PF-46396, was recently reported to have a similar
      mode of action to that of BVM. Because of the structural dissimilarity between
      BVM and PF-46396, we hypothesized that the two compounds might interact
      differentially with the putative maturation inhibitor-binding pocket in Gag. To
      test this hypothesis, PF-46396 resistance was selected for in vitro. Resistance
      mutations were identified in three regions of Gag: around the CA-SP1 cleavage
      site where BVM resistance maps, at CA amino acid 201, and in the CA major
      homology region (MHR). The MHR mutants are profoundly PF-46396-dependent in Gag
      assembly and release and virus replication. The severe defect exhibited by the
      inhibitor-dependent MHR mutants in the absence of the compound is also corrected
      by a second-site compensatory change far downstream in SP1, suggesting structural
      and functional cross-talk between the HIV-1 CA MHR and SP1. When PF-46396 and BVM
      were both present in infected cells they exhibited mutually antagonistic
      behavior. Together, these results identify Gag residues that line the maturation
      inhibitor-binding pocket and suggest that BVM and PF-46396 interact
      differentially with this putative pocket. These findings provide novel insights
      into the structure-function relationship between the CA MHR and SP1, two domains
      of Gag that are critical to both assembly and maturation. The highly conserved
      nature of the MHR across all orthoretroviridae suggests that these findings will
      be broadly relevant to retroviral assembly. Finally, the results presented here
      provide a framework for increased structural understanding of HIV-1 maturation
      inhibitor activity.

PMID- 23144616
TI  - Vaccines: from empirical development to rational design.
AB  - Infectious diseases are responsible for an overwhelming number of deaths
      worldwide and their clinical management is often hampered by the emergence of
      multi-drug-resistant strains. Therefore, prevention through vaccination currently
      represents the best course of action to combat them. However, immune escape and
      evasion by pathogens often render vaccine development difficult. Furthermore,
      most currently available vaccines were empirically designed. In this review, we
      discuss why rational design of vaccines is not only desirable but also necessary.
      We introduce recent developments towards specifically tailored antigens,
      adjuvants, and delivery systems, and discuss the methodological gaps and lack of
      knowledge still hampering true rational vaccine design. Finally, we address the
      potential and limitations of different strategies and technologies for advancing
      vaccine development.

PMID- 23144618
TI  - Arabidopsis Actin-Depolymerizing Factor-4 links pathogen perception, defense
      activation and transcription to cytoskeletal dynamics.
AB  - The primary role of Actin-Depolymerizing Factors (ADFs) is to sever filamentous
      actin, generating pointed ends, which in turn are incorporated into newly formed
      filaments, thus supporting stochastic actin dynamics. Arabidopsis ADF4 was
      recently shown to be required for the activation of resistance in Arabidopsis
      following infection with the phytopathogenic bacterium Pseudomonas syringae pv.
      tomato DC3000 (Pst) expressing the effector protein AvrPphB. Herein, we
      demonstrate that the expression of RPS5, the cognate resistance protein of
      AvrPphB, was dramatically reduced in the adf4 mutant, suggesting a link between
      actin cytoskeletal dynamics and the transcriptional regulation of R-protein
      activation. By examining the PTI (PAMP Triggered Immunity) response in the adf4
      mutant when challenged with Pst expressing AvrPphB, we observed a significant
      reduction in the expression of the PTI-specific target gene FRK1 (Flg22-Induced
      Receptor Kinase 1). These data are in agreement with recent observations
      demonstrating a requirement for RPS5 in PTI-signaling in the presence of AvrPphB.
      Furthermore, MAPK (Mitogen-Activated Protein Kinase)-signaling was significantly
      reduced in the adf4 mutant, while no such reduction was observed in the rps5-1
      point mutation under similar conditions. Isoelectric focusing confirmed
      phosphorylation of ADF4 at serine-6, and additional in planta analyses of ADF4's
      role in immune signaling demonstrates that nuclear localization is
      phosphorylation independent, while localization to the actin cytoskeleton is
      linked to ADF4 phosphorylation. Taken together, these data suggest a novel role
      for ADF4 in controlling gene-for-gene resistance activation, as well as MAPK
      signaling, via the coordinated regulation of actin cytoskeletal dynamics and R
      gene transcription.

PMID- 23144617
TI  - Early mechanisms of pathobiology are revealed by transcriptional temporal
      dynamics in hippocampal CA1 neurons of prion infected mice.
AB  - Prion diseases typically have long pre-clinical incubation periods during which
      time the infectious prion particle and infectivity steadily propagate in the
      brain. Abnormal neuritic sprouting and synaptic deficits are apparent during pre
      clinical disease, however, gross neuronal loss is not detected until the onset of
      the clinical phase. The molecular events that accompany early neuronal damage and
      ultimately conclude with neuronal death remain obscure. In this study, we used
      laser capture microdissection to isolate hippocampal CA1 neurons and determined
      their pre-clinical transcriptional response during infection. We found that gene
      expression within these neurons is dynamic and characterized by distinct phases
      of activity. We found that a major cluster of genes is altered during pre
      clinical disease after which expression either returns to basal levels, or
      alternatively undergoes a direct reversal during clinical disease. Strikingly, we
      show that this cluster contains a signature highly reminiscent of synaptic N
      methyl-D-aspartic acid (NMDA) receptor signaling and the activation of
      neuroprotective pathways. Additionally, genes involved in neuronal projection and
      dendrite development were also altered throughout the disease, culminating in a
      general decline of gene expression for synaptic proteins. Similarly, deregulated
      miRNAs such as miR-132-3p, miR-124a-3p, miR-16-5p, miR-26a-5p, miR-29a-3p and miR
      140-5p follow concomitant patterns of expression. This is the first in depth
      genomic study describing the pre-clinical response of hippocampal neurons to
      early prion replication. Our findings suggest that prion replication results in
      the persistent stimulation of a programmed response that is mediated, at least in
      part, by synaptic NMDA receptor activity that initially promotes cell survival
      and neurite remodelling. However, this response is terminated prior to the onset
      of clinical symptoms in the infected hippocampus, seemingly pointing to a
      critical juncture in the disease. Manipulation of these early neuroprotective
      pathways may redress the balance between degeneration and survival, providing a
      potential inroad for treatment.

PMID- 23144619
TI  - Changes in JC virus-specific T cell responses during natalizumab treatment and in
      natalizumab-associated progressive multifocal leukoencephalopathy.
AB  - Progressive multifocal leukoencephalopathy (PML) induced by JC virus (JCV) is a
      risk for natalizumab-treated multiple sclerosis (MS) patients. Here we
      characterize the JCV-specific T cell responses in healthy donors and natalizumab
      treated MS patients to reveal functional differences that may account for the
      development of natalizumab-associated PML. CD4 and CD8 T cell responses specific
      for all JCV proteins were readily identified in MS patients and healthy
      volunteers. The magnitude and quality of responses to JCV and cytomegalovirus
      (CMV) did not change from baseline through several months of natalizumab therapy.
      However, the frequency of T cells producing IL-10 upon mitogenic stimulation
      transiently increased after the first dose. In addition, MS patients with
      natalizumab-associated PML were distinguished from all other subjects in that
      they either had no detectable JCV-specific T cell response or had JCV-specific
      CD4 T cell responses uniquely dominated by IL-10 production. Additionally, IL-10
      levels were higher in the CSF of individuals with recently diagnosed PML. Thus,
      natalizumab-treated MS patients with PML have absent or aberrant JCV-specific T
      cell responses compared with non-PML patients, and changes in T cell-mediated
      control of JCV replication may be a risk factor for developing PML. Our data
      suggest further approaches to improved monitoring, treatment and prevention of
      PML in natalizumab-treated patients.

PMID- 23144620
TI  - Genome structure and reproductive behaviour influence the evolutionary potential
      of a fungal phytopathogen.
AB  - Modern agriculture favours the selection and spread of novel plant diseases.
      Furthermore, crop genetic resistance against pathogens is often rendered
      ineffective within a few years of its commercial deployment. Leptosphaeria
      maculans, the cause of phoma stem canker of oilseed rape, develops gene-for-gene
      interactions with its host plant, and has a high evolutionary potential to render
      ineffective novel sources of resistance in crops. Here, we established a four
      year field experiment to monitor the evolution of populations confronted with the
      newly released Rlm7 resistance and to investigate the nature of the mutations
      responsible for virulence against Rlm7. A total of 2551 fungal isolates were
      collected from experimental crops of a Rlm7 cultivar or a cultivar without Rlm7.
      All isolates were phenotyped for virulence and a subset was genotyped with
      neutral genetic markers. Virulent isolates were investigated for molecular events
      at the AvrLm4-7 locus. Whilst virulent isolates were not found in neighbouring
      crops, their frequency had reached 36% in the experimental field after four
      years. An extreme diversity of independent molecular events leading to virulence
      was identified in populations, with large-scale Repeat Induced Point mutations or
      complete deletion of AvrLm4-7 being the most frequent. Our data suggest that
      increased mutability of fungal genes involved in the interactions with plants is
      directly related to their genomic environment and reproductive system. Thus,
      rapid allelic diversification of avirulence genes can be generated in L. maculans
      populations in a single field provided that large population sizes and sexual
      reproduction are favoured by agricultural practices.

PMID- 23144621
TI  - Bromodomain protein Brd4 plays a key role in Merkel cell polyomavirus DNA
      replication.
AB  - Merkel cell polyomavirus (MCV or MCPyV) is the first human polyomavirus to be
      definitively linked to cancer. The mechanisms of MCV-induced oncogenesis and much
      of MCV biology are largely unexplored. In this study, we demonstrate that
      bromodomain protein 4 (Brd4) interacts with MCV large T antigen (LT) and plays a
      critical role in viral DNA replication. Brd4 knockdown inhibits MCV replication,
      which can be rescued by recombinant Brd4. Brd4 colocalizes with the MCV
      LT/replication origin complex in the nucleus and recruits replication factor C
      (RFC) to the viral replication sites. A dominant negative inhibitor of the Brd4
      MCV LT interaction can dissociate Brd4 and RFC from the viral replication complex
      and abrogate MCV replication. Furthermore, obstructing the physiologic
      interaction between Brd4 and host chromatin with the chemical compound JQ1(+)
      leads to enhanced MCV DNA replication, demonstrating that the role of Brd4 in MCV
      replication is distinct from its role in chromatin-associated transcriptional
      regulation. Our findings demonstrate mechanistic details of the MCV replication
      machinery; providing novel insight to elucidate the life cycle of this newly
      discovered oncogenic DNA virus.

PMID- 23144622
TI  - Identification of the first ATRIP-deficient patient and novel mutations in ATR
      define a clinical spectrum for ATR-ATRIP Seckel Syndrome.
AB  - A homozygous mutational change in the Ataxia-Telangiectasia and RAD3 related
      (ATR) gene was previously reported in two related families displaying Seckel
      Syndrome (SS). Here, we provide the first identification of a Seckel Syndrome
      patient with mutations in ATRIP, the gene encoding ATR-Interacting Protein
      (ATRIP), the partner protein of ATR required for ATR stability and recruitment to
      the site of DNA damage. The patient has compound heterozygous mutations in ATRIP
      resulting in reduced ATRIP and ATR expression. A nonsense mutational change in
      one ATRIP allele results in a C-terminal truncated protein, which impairs ATR
      ATRIP interaction; the other allele is abnormally spliced. We additionally
      describe two further unrelated patients native to the UK with the same novel,
      heterozygous mutations in ATR, which cause dramatically reduced ATR expression.
      All patient-derived cells showed defective DNA damage responses that can be
      attributed to impaired ATR-ATRIP function. Seckel Syndrome is characterised by
      microcephaly and growth delay, features also displayed by several related
      disorders including Majewski (microcephalic) osteodysplastic primordial dwarfism
      (MOPD) type II and Meier-Gorlin Syndrome (MGS). The identification of an ATRIP
      deficient patient provides a novel genetic defect for Seckel Syndrome. Coupled
      with the identification of further ATR-deficient patients, our findings allow a
      spectrum of clinical features that can be ascribed to the ATR-ATRIP deficient sub
      class of Seckel Syndrome. ATR-ATRIP patients are characterised by extremely
      severe microcephaly and growth delay, microtia (small ears), micrognathia (small
      and receding chin), and dental crowding. While aberrant bone development was mild
      in the original ATR-SS patient, some of the patients described here display
      skeletal abnormalities including, in one patient, small patellae, a feature
      characteristically observed in Meier-Gorlin Syndrome. Collectively, our analysis
      exposes an overlapping clinical manifestation between the disorders but allows an
      expanded spectrum of clinical features for ATR-ATRIP Seckel Syndrome to be
      defined.

PMID- 23144623
TI  - Evolutionarily ancient association of the FoxJ1 transcription factor with the
      motile ciliogenic program.
AB  - It is generally believed that the last eukaryotic common ancestor (LECA) was a
      unicellular organism with motile cilia. In the vertebrates, the winged-helix
      transcription factor FoxJ1 functions as the master regulator of motile cilia
      biogenesis. Despite the antiquity of cilia, their highly conserved structure, and
      their mechanism of motility, the evolution of the transcriptional program
      controlling ciliogenesis has remained incompletely understood. In particular, it
      is presently not known how the generation of motile cilia is programmed outside
      of the vertebrates, and whether and to what extent the FoxJ1-dependent regulation
      is conserved. We have performed a survey of numerous eukaryotic genomes and
      discovered that genes homologous to foxJ1 are restricted only to organisms
      belonging to the unikont lineage. Using a mis-expression assay, we then obtained
      evidence of a conserved ability of FoxJ1 proteins from a number of diverse
      phyletic groups to activate the expression of a host of motile ciliary genes in
      zebrafish embryos. Conversely, we found that inactivation of a foxJ1 gene in
      Schmidtea mediterranea, a platyhelminth (flatworm) that utilizes motile cilia for
      locomotion, led to a profound disruption in the differentiation of motile cilia.
      Together, all of these findings provide the first evolutionary perspective into
      the transcriptional control of motile ciliogenesis and allow us to propose a
      conserved FoxJ1-regulated mechanism for motile cilia biogenesis back to the
      origin of the metazoans.

PMID- 23144624
TI  - Loss of prohibitin membrane scaffolds impairs mitochondrial architecture and
      leads to tau hyperphosphorylation and neurodegeneration.
AB  - Fusion and fission of mitochondria maintain the functional integrity of
      mitochondria and protect against neurodegeneration, but how mitochondrial
      dysfunctions trigger neuronal loss remains ill-defined. Prohibitins form large
      ring complexes in the inner membrane that are composed of PHB1 and PHB2 subunits
      and are thought to function as membrane scaffolds. In Caenorhabditis elegans,
      prohibitin genes affect aging by moderating fat metabolism and energy production.
      Knockdown experiments in mammalian cells link the function of prohibitins to
      membrane fusion, as they were found to stabilize the dynamin-like GTPase OPA1
      (optic atrophy 1), which mediates mitochondrial inner membrane fusion and cristae
      morphogenesis. Mutations in OPA1 are associated with dominant optic atrophy
      characterized by the progressive loss of retinal ganglion cells, highlighting the
      importance of OPA1 function in neurons. Here, we show that neuron-specific
      inactivation of Phb2 in the mouse forebrain causes extensive neurodegeneration
      associated with behavioral impairments and cognitive deficiencies. We observe
      early onset tau hyperphosphorylation and filament formation in the hippocampus,
      demonstrating a direct link between mitochondrial defects and tau pathology. Loss
      of PHB2 impairs the stability of OPA1, affects mitochondrial ultrastructure, and
      induces the perinuclear clustering of mitochondria in hippocampal neurons. A
      destabilization of the mitochondrial genome and respiratory deficiencies manifest
      in aged neurons only, while the appearance of mitochondrial morphology defects
      correlates with tau hyperphosphorylation in the absence of PHB2. These results
      establish an essential role of prohibitin complexes for neuronal survival in vivo
      and demonstrate that OPA1 stability, mitochondrial fusion, and the maintenance of
      the mitochondrial genome in neurons depend on these scaffolding proteins.
      Moreover, our findings establish prohibitin-deficient mice as a novel genetic
      model for tau pathologies caused by a dysfunction of mitochondria and raise the
      possibility that tau pathologies are associated with other neurodegenerative
      disorders caused by deficiencies in mitochondrial dynamics.

PMID- 23144625
TI  - Microhomology directs diverse DNA break repair pathways and chromosomal
      translocations.
AB  - Chromosomal structural change triggers carcinogenesis and the formation of other
      genetic diseases. The breakpoint junctions of these rearrangements often contain
      small overlapping sequences called "microhomology," yet the genetic pathway(s)
      responsible have yet to be defined. We report a simple genetic system to detect
      microhomology-mediated repair (MHMR) events after a DNA double-strand break (DSB)
      in budding yeast cells. MHMR using >15 bp operates as a single-strand annealing
      variant, requiring the non-essential DNA polymerase subunit Pol32. MHMR is
      inhibited by sequence mismatches, but independent of extensive DNA synthesis like
      break-induced replication. However, MHMR using less than 14 bp is genetically
      distinct from that using longer microhomology and far less efficient for the
      repair of distant DSBs. MHMR catalyzes chromosomal translocation almost as
      efficiently as intra-chromosomal repair. The results suggest that the intrinsic
      annealing propensity between microhomology sequences efficiently leads to
      chromosomal rearrangements.

PMID- 23144626
TI  - Mechanisms employed by Escherichia coli to prevent ribonucleotide incorporation
      into genomic DNA by Pol V.
AB  - Escherichia coli pol V (UmuD'(2)C), the main translesion DNA polymerase, ensures
      continued nascent strand extension when the cellular replicase is blocked by
      unrepaired DNA lesions. Pol V is characterized by low sugar selectivity, which
      can be further reduced by a Y11A "steric-gate" substitution in UmuC that enables
      pol V to preferentially incorporate rNTPs over dNTPs in vitro. Despite efficient
      error-prone translesion synthesis catalyzed by UmuC_Y11A in vitro, strains
      expressing umuC_Y11A exhibit low UV mutability and UV resistance. Here, we show
      that these phenotypes result from the concomitant dual actions of Ribonuclease
      HII (RNase HII) initiating removal of rNMPs from the nascent DNA strand and
      nucleotide excision repair (NER) removing UV lesions from the parental strand. In
      the absence of either repair pathway, UV resistance and mutagenesis conferred by
      umuC_Y11A is significantly enhanced, suggesting that the combined actions of
      RNase HII and NER lead to double-strand breaks that result in reduced cell
      viability. We present evidence that the Y11A-specific UV phenotype is tempered by
      pol IV in vivo. At physiological ratios of the two polymerases, pol IV inhibits
      pol V-catalyzed translesion synthesis (TLS) past UV lesions and significantly
      reduces the number of Y11A-incorporated rNTPs by limiting the length of the pol V
      dependent TLS tract generated during lesion bypass in vitro. In a recA730
      lexA(Def) DeltaumuDC DeltadinB strain, plasmid-encoded wild-type pol V promotes
      high levels of spontaneous mutagenesis. However, umuC_Y11A-dependent spontaneous
      mutagenesis is only ~7% of that observed with wild-type pol V, but increases to
      ~39% of wild-type levels in an isogenic DeltarnhB strain and ~72% of wild-type
      levels in a DeltarnhA DeltarnhB double mutant. Our observations suggest that
      errant ribonucleotides incorporated by pol V can be tolerated in the E. coli
      genome, but at the cost of higher levels of cellular mutagenesis.

PMID- 23144627
TI  - A targeted glycan-related gene screen reveals heparan sulfate proteoglycan
      sulfation regulates WNT and BMP trans-synaptic signaling.
AB  - A Drosophila transgenic RNAi screen targeting the glycan genome, including all
      N/O/GAG-glycan biosynthesis/modification enzymes and glycan-binding lectins, was
      conducted to discover novel glycan functions in synaptogenesis. As proof-of
      product, we characterized functionally paired heparan sulfate (HS) 6-O
      sulfotransferase (hs6st) and sulfatase (sulf1), which bidirectionally control HS
      proteoglycan (HSPG) sulfation. RNAi knockdown of hs6st and sulf1 causes opposite
      effects on functional synapse development, with decreased (hs6st) and increased
      (sulf1) neurotransmission strength confirmed in null mutants. HSPG co-receptors
      for WNT and BMP intercellular signaling, Dally-like Protein and Syndecan, are
      differentially misregulated in the synaptomatrix of these mutants. Consistently,
      hs6st and sulf1 nulls differentially elevate both WNT (Wingless; Wg) and BMP
      (Glass Bottom Boat; Gbb) ligand abundance in the synaptomatrix. Anterograde Wg
      signaling via Wg receptor dFrizzled2 C-terminus nuclear import and retrograde Gbb
      signaling via synaptic MAD phosphorylation and nuclear import are differentially
      activated in hs6st and sulf1 mutants. Consequently, transcriptional control of
      presynaptic glutamate release machinery and postsynaptic glutamate receptors is
      bidirectionally altered in hs6st and sulf1 mutants, explaining the bidirectional
      change in synaptic functional strength. Genetic correction of the altered WNT/BMP
      signaling restores normal synaptic development in both mutant conditions, proving
      that altered trans-synaptic signaling causes functional differentiation defects.

PMID- 23144628
TI  - Informed conditioning on clinical covariates increases power in case-control
      association studies.
AB  - Genetic case-control association studies often include data on clinical
      covariates, such as body mass index (BMI), smoking status, or age, that may
      modify the underlying genetic risk of case or control samples. For example, in
      type 2 diabetes, odds ratios for established variants estimated from low-BMI
      cases are larger than those estimated from high-BMI cases. An unanswered question
      is how to use this information to maximize statistical power in case-control
      studies that ascertain individuals on the basis of phenotype (case-control
      ascertainment) or phenotype and clinical covariates (case-control-covariate
      ascertainment). While current approaches improve power in studies with random
      ascertainment, they often lose power under case-control ascertainment and fail to
      capture available power increases under case-control-covariate ascertainment. We
      show that an informed conditioning approach, based on the liability threshold
      model with parameters informed by external epidemiological information, fully
      accounts for disease prevalence and non-random ascertainment of phenotype as well
      as covariates and provides a substantial increase in power while maintaining a
      properly controlled false-positive rate. Our method outperforms standard case
      control association tests with or without covariates, tests of gene x covariate
      interaction, and previously proposed tests for dealing with covariates in
      ascertained data, with especially large improvements in the case of case-control
      covariate ascertainment. We investigate empirical case-control studies of type 2
      diabetes, prostate cancer, lung cancer, breast cancer, rheumatoid arthritis, age
      related macular degeneration, and end-stage kidney disease over a total of 89,726
      samples. In these datasets, informed conditioning outperforms logistic regression
      for 115 of the 157 known associated variants investigated (P-value = 1 * 10(-9)).
      The improvement varied across diseases with a 16% median increase in chi(2) test
      statistics and a commensurate increase in power. This suggests that applying our
      method to existing and future association studies of these diseases may identify
      novel disease loci.

PMID- 23144629
TI  - The DNA replication factor RFC1 is required for interference-sensitive meiotic
      crossovers in Arabidopsis thaliana.
AB  - During meiotic recombination, induced double-strand breaks (DSBs) are processed
      into crossovers (COs) and non-COs (NCO); the former are required for proper
      chromosome segregation and fertility. DNA synthesis is essential in current
      models of meiotic recombination pathways and includes only leading strand DNA
      synthesis, but few genes crucial for DNA synthesis have been tested genetically
      for their functions in meiosis. Furthermore, lagging strand synthesis has been
      assumed to be unnecessary. Here we show that the Arabidopsis thaliana DNA
      replication factor C1 (RFC1) important for lagging strand synthesis is necessary
      for fertility, meiotic bivalent formation, and homolog segregation. Loss of
      meiotic RFC1 function caused abnormal meiotic chromosome association and other
      cytological defects; genetic analyses with other meiotic mutations indicate that
      RFC1 acts in the MSH4-dependent interference-sensitive pathway for CO formation.
      In a rfc1 mutant, residual pollen viability is MUS81-dependent and COs exhibit
      essentially no interference, indicating that these COs form via the MUS81
      dependent interference-insensitive pathway. We hypothesize that lagging strand
      DNA synthesis is important for the formation of double Holliday junctions, but
      not alternative recombination intermediates. That RFC1 is found in divergent
      eukaryotes suggests a previously unrecognized and highly conserved role for DNA
      synthesis in discriminating between recombination pathways.

PMID- 23144630
TI  - CNOT3 is a modifier of PRPF31 mutations in retinitis pigmentosa with incomplete
      penetrance.
AB  - Heterozygous mutations in the PRPF31 gene cause autosomal dominant retinitis
      pigmentosa (adRP), a hereditary disorder leading to progressive blindness. In
      some cases, such mutations display incomplete penetrance, implying that certain
      carriers develop retinal degeneration while others have no symptoms at all.
      Asymptomatic carriers are protected from the disease by a higher than average
      expression of the PRPF31 allele that is not mutated, mainly through the action of
      an unknown modifier gene mapping to chromosome 19q13.4. We investigated a large
      family with adRP segregating an 11-bp deletion in PRPF31. The analysis of cell
      lines derived from asymptomatic and affected individuals revealed that the
      expression of only one gene among a number of candidates within the 19q13.4
      interval significantly correlated with that of PRPF31, both at the mRNA and
      protein levels, and according to an inverse relationship. This gene was CNOT3,
      encoding a subunit of the Ccr4-not transcription complex. In cultured cells,
      siRNA-mediated silencing of CNOT3 provoked an increase in PRPF31 expression,
      confirming a repressive nature of CNOT3 on PRPF31. Furthermore, chromatin
      immunoprecipitation revealed that CNOT3 directly binds to a specific PRPF31
      promoter sequence, while next-generation sequencing of the CNOT3 genomic region
      indicated that its variable expression is associated with a common intronic SNP.
      In conclusion, we identify CNOT3 as the main modifier gene determining penetrance
      of PRPF31 mutations, via a mechanism of transcriptional repression. In
      asymptomatic carriers CNOT3 is expressed at low levels, allowing higher amounts
      of wild-type PRPF31 transcripts to be produced and preventing manifestation of
      retinal degeneration.

PMID- 23144631
TI  - Notch-mediated suppression of TSC2 expression regulates cell differentiation in
      the Drosophila intestinal stem cell lineage.
AB  - Epithelial homeostasis in the posterior midgut of Drosophila is maintained by
      multipotent intestinal stem cells (ISCs). ISCs self-renew and produce
      enteroblasts (EBs) that differentiate into either enterocytes (ECs) or
      enteroendocrine cells (EEs) in response to differential Notch (N) activation.
      Various environmental and growth signals dynamically regulate ISC activity, but
      their integration with differentiation cues in the ISC lineage remains unclear.
      Here we identify Notch-mediated repression of Tuberous Sclerosis Complex 2 (TSC2)
      in EBs as a required step in the commitment of EBs into the EC fate. The TSC1/2
      complex inhibits TOR signaling, acting as a tumor suppressor in vertebrates and
      regulating cell growth. We find that TSC2 is expressed highly in ISCs, where it
      maintains stem cell identity, and that N-mediated repression of TSC2 in EBs is
      required and sufficient to promote EC differentiation. Regulation of TSC/TOR
      activity by N signaling thus emerges as critical for maintenance and
      differentiation in somatic stem cell lineages.

PMID- 23144632
TI  - A combination of H2A.Z and H4 acetylation recruits Brd2 to chromatin during
      transcriptional activation.
AB  - H2A.Z is an essential histone variant that has been implicated to have multiple
      chromosomal functions. To understand how H2A.Z participates in such diverse
      activities, we sought to identify downstream effector proteins that are recruited
      to chromatin via H2A.Z. For this purpose, we developed a nucleosome purification
      method to isolate H2A.Z-containing nucleosomes from human cells and used mass
      spectrometry to identify the co-purified nuclear proteins. Through stringent
      filtering, we identified the top 21 candidates, many of which have conserved
      structural motifs that bind post-translationally modified histones. We further
      validated the biological significance of one such candidate, Brd2, which is a
      double-bromodomain-containing protein known to function in transcriptional
      activation. We found that Brd2's preference for H2A.Z nucleosomes is mediated
      through a combination of hyperacetylated H4 on these nucleosomes, as well as
      additional features on H2A.Z itself. In addition, comparison of nucleosomes
      containing either H2A.Z-1 or H2A.Z-2 isoforms showed that significantly more Brd2
      co-purifies with the former, suggesting these two isoforms engage different
      downstream effector proteins. Consistent with these biochemical analyses, we
      found that Brd2 is recruited to AR-regulated genes in an H2A.Z-dependent manner
      and that chemical inhibition of Brd2 recruitment greatly inhibits AR-regulated
      gene expression. Taken together, we propose that Brd2 is a key downstream
      mediator that links H2A.Z and transcriptional activation of AR-regulated genes.
      Moreover, this study validates the approach of using proteomics to identify
      nucleosome-interacting proteins in order to elucidate downstream mechanistic
      functions associated with the histone variant H2A.Z.

PMID- 23144633
TI  - Transcription factor Oct1 is a somatic and cancer stem cell determinant.
AB  - Defining master transcription factors governing somatic and cancer stem cell
      identity is an important goal. Here we show that the Oct4 paralog Oct1, a
      transcription factor implicated in stress responses, metabolic control, and
      poised transcription states, regulates normal and pathologic stem cell function.
      Oct1(HI) cells in the colon and small intestine co-express known stem cell
      markers. In primary malignant tissue, high Oct1 protein but not mRNA levels
      strongly correlate with the frequency of CD24(LO)CD44(HI) cancer-initiating
      cells. Reducing Oct1 expression via RNAi reduces the proportion of ALDH(HI) and
      dye efflux(HI) cells, and increasing Oct1 increases the proportion of ALDH(HI)
      cells. Normal ALDH(HI) cells harbor elevated Oct1 protein but not mRNA levels.
      Functionally, we show that Oct1 promotes tumor engraftment frequency and promotes
      hematopoietic stem cell engraftment potential in competitive and serial
      transplants. In addition to previously described Oct1 transcriptional targets, we
      identify four Oct1 targets associated with the stem cell phenotype. Cumulatively,
      the data indicate that Oct1 regulates normal and cancer stem cell function.

PMID- 23144635
TI  - A germline polymorphism of DNA polymerase beta induces genomic instability and
      cellular transformation.
AB  - Several germline single nucleotide polymorphisms (SNPs) have been identified in
      the POLB gene, but little is known about their cellular and biochemical impact.
      DNA Polymerase beta (Pol beta), encoded by the POLB gene, is the main gap-filling
      polymerase involved in base excision repair (BER), a pathway that protects the
      genome from the consequences of oxidative DNA damage. In this study we tested the
      hypothesis that expression of the POLB germline coding SNP (rs3136797) in
      mammalian cells could induce a cancerous phenotype. Expression of this SNP in
      both human and mouse cells induced double-strand breaks, chromosomal aberrations,
      and cellular transformation. Following treatment with an alkylating agent, cells
      expressing this coding SNP accumulated BER intermediate substrates, including
      single-strand and double-strand breaks. The rs3136797 SNP encodes the P242R
      variant Pol beta protein and biochemical analysis showed that P242R protein had a
      slower catalytic rate than WT, although P242R binds DNA similarly to WT. Our
      results suggest that people who carry the rs3136797 germline SNP may be at an
      increased risk for cancer susceptibility.

PMID- 23144634
TI  - CtIP is required to initiate replication-dependent interstrand crosslink repair.
AB  - DNA interstrand crosslinks (ICLs) are toxic lesions that block the progression of
      replication and transcription. CtIP is a conserved DNA repair protein that
      facilitates DNA end resection in the double-strand break (DSB) repair pathway.
      Here we show that CtIP plays a critical role during initiation of ICL processing
      in replicating human cells that is distinct from its role in DSB repair. CtIP
      depletion sensitizes human cells to ICL inducing agents and significantly impairs
      the accumulation of DNA damage response proteins RPA, ATR, FANCD2, gammaH2AX, and
      phosphorylated ATM at sites of laser generated ICLs. In contrast, the appearance
      of gammaH2AX and phosphorylated ATM at sites of laser generated double strand
      breaks (DSBs) is CtIP-independent. We present a model in which CtIP functions
      early in ICL repair in a BRCA1- and FANCM-dependent manner prior to generation of
      DSB repair intermediates.

PMID- 23144637
TI  - Recurrence of dislocation following total hip arthroplasty revision using dual
      mobility cups was rare in 180 hips followed over 7 years.
AB  - BACKGROUND: Dual mobility (DM) cups of mobile polyethylene were introduced to
      prevent total hip arthroplasty (THA) dislocation, but no large series with this
      design to treat recurrent instability have been reported. PURPOSE: Our
      retrospective investigation ascertained the efficiency of DM cups in correction
      of recurrent dislocation and assessed any adverse effects. METHODS: One hundred
      eighty THAs with recurrent instability were revised to DM cups in 180 patients
      (mean age, 67.4 +/- 11.7 years; range, 19 to 92 years). Thirty-one patients
      (17.2%) underwent at least one earlier THA revision, and 15 (10.3%) incurred non
      union of the greater trochanter. Of the initial group in 2009, 145 patients had
      completed evaluations which included assessment of the Harris Hip Score and a
      radiographic assessment at a mean follow-up of 7.7 +/- 2.2 years (range, 4 to 14
      years). The rate of survival was calculated considering any reason for revision
      as failure. RESULTS: At follow-up, Harris hip score was 83.9 +/- 16.1 (range, 21
      to 100). Dislocation of the large articulation occurred in seven hips (4.8%), and
      only two recurred (1.4%) (one requiring additional revision). In addition, two
      intra-prosthetic dislocations of the small articulation (1.4%) were observed and
      needed revision surgery. The large number of earlier surgeries and non-union of
      the greater trochanter were related to recurrent instability. Two cups (1.4%)
      showed signs of definite loosening; six (4.1%) presented signs of possible
      loosening. Twenty-nine hips manifested femoral or acetabular osteolysis (20%),
      but only three were severe. Eight-year survival rate considering revision for any
      reason was 92.6% (95% CI, 85.5-96.4%). CONCLUSIONS: This series indicates that DM
      cups are a viable option to treat recurrent THA instability. Their design
      provides a low risk of recurrent instability without increasing mechanical
      complications.

PMID- 23144638
TI  - The application of genetics methods to differentiation of three Lactobacillus
      species of human origin.
AB  - In recent decades, the interest in probiotics as diet supplements or drugs has
      increased. In order to determine a specific bacterial isolate to be probiotic, it
      is necessary to describe precisely its probiotic characteristics and taxonomic
      properties, including the strain level. Most of the well-known genotyping methods
      were designed for the commonly-found pathogenic bacteria. The objective of this
      study is to undertake an attempt at standardization of FISH, RAPD and PFGE
      methods to genotype and identify the bacteria belonging to Lactobacillus
      fermentum, L. gasseri and L. plantarum species. The FISH probes have been
      designed and tested for Lactobacillus fermentum, L. gasseri and L. plantarum
      species and an endeavor has been made at standardization of RAPD and PFGE methods
      for these bacterial species. Moreover, the MLST method was applied to
      differentiate Lactobacillus plantarum strains. L. plantarum isolated from humans
      could not be genetically diversified with the use of RAPD, PFGE or MLST methods;
      only the strains originating from plants have displayed diversification among
      themselves and have been different from the strains of human origin.

PMID- 23144636
TI  - Genome instability caused by a germline mutation in the human DNA repair gene
      POLB.

PMID- 23144639
TI  - Prevention of adhesions in gynaecological surgery: the 2012 European field
      guideline.
AB  - Postoperative adhesions have become the most common complication of open or
      laparoscopic abdominal surgery and a source of major concern because of their
      potentially dramatic consequences. The proposed guideline is the beginning of a
      major campaign to enhance the awareness of adhesions and to provide surgeons with
      a reference guide to adhesion prevention adapted to the conditions of their daily
      practice. The risk of postoperative adhesions should be systematically discussed
      with any patient scheduled for open or laparoscopic abdominal surgery prior to
      obtaining her informed consent. Surgeons should adopt a routine adhesion
      reduction strategy with good surgical technique. Anti-adhesion agents are an
      additional option, especially in procedures with a high risk of adhesion
      formation, such as ovarian, endometriosis and tubal surgery and myomectomy. We
      conclude that good surgical practice is paramount to reduce adhesion formation
      and that anti-adhesion agents may contribute to adhesion prevention in certain
      cases.

PMID- 23144640
TI  - Vaginal cuff dehiscence in laparoscopic hysterectomy: influence of various
      suturing methods of the vaginal vault.
AB  - Vaginal cuff dehiscence (VCD) is a severe adverse event and occurs more
      frequently after total laparoscopic hysterectomy (TLH) compared with abdominal
      and vaginal hysterectomy. The aim of this study is to compare the incidence of
      VCD after various suturing methods to close the vaginal vault. We conducted a
      retrospective cohort study. Patients who underwent TLH between January 2004 and
      May 2011 were enrolled. We compared the incidence of VCD after closure with
      transvaginal interrupted sutures versus laparoscopic interrupted sutures versus a
      laparoscopic single-layer running suture. The latter was either bidirectional
      barbed or a running vicryl suture with clips placed at each end commonly used in
      transanal endoscopic microsurgery. Three hundred thirty-one TLHs were included.
      In 75 (22.7 %), the vaginal vault was closed by transvaginal approach; in 90
      (27.2 %), by laparoscopic interrupted sutures; and in 166 (50.2 %), by a
      laparoscopic running suture. Eight VCDs occurred: one (1.3 %) after transvaginal
      interrupted closure, three (3.3 %) after laparoscopic interrupted suturing and
      four (2.4 %) after a laparoscopic running suture was used (p = .707). With regard
      to the incidence of VCD, based on our data, neither a superiority of single-layer
      laparoscopic closure of the vaginal cuff with an unknotted running suture nor of
      the transvaginal and the laparoscopic interrupted suturing techniques could be
      demonstrated. We hypothesise that besides the suturing technique, other causes,
      such as the type and amount of coagulation used for colpotomy, may play a role in
      the increased risk of VCD after TLH.

PMID- 23144641
TI  - Ectopic pregnancy: when is expectant management safe?
AB  - This study was conducted to evaluate expectant management in asymptomatic
      patients with an initial serum beta-hCG titer of <2,500 IU/l and to determine the
      independent ability of initial serum beta-hCG titers and trend of serum beta-hCG
      to predict successful expectant management. A cohort of patients (N = 418) with
      suspected ectopic pregnancy (EP) between January 1991 and July 2008 is described.
      Three groups were defined: group I (n = 182), immediate surgical intervention
      (<24 h); group IIa (n = 130), unsuccessful expectant management (surgical
      intervention during follow-up), and group IIb (n = 99), successful expectant
      management (spontaneous regression of trophoblast). Hospital protocol was not
      complied in 35 cases (Table 1). Beta-hCG levels >3,000 IU/l occur in our
      expectant management group; however, none of these cases were successful.
      Unnecessary surgery was prevented in 14% (n = 7) of asymptomatic patients with
      initial beta-hCG of >2,000 IU/l. The success rate of expectant management was
      49%, without a rise in complication rate or number of acute cases. In conclusion,
      the initial serum beta-hCG cutoff level of 2,000 IU/l is not a rigid upper limit
      for accepting expectant management in suspected EP and best practice is case
      specific. In asymptomatic patients, the serum beta-hCG cutoff level of at least
      2,500 IU/l can be used for expectant management. This cutoff could be higher, but
      interpretation is limited due to censure in follow-up inherent to the predefined
      clinical protocol. There is no gain in including patients for expectant
      management with initial serum beta-hCG level >3,000 IU/l.

PMID- 23144642
TI  - Strength of sliding knots in multifilament resorbable suture materials.
AB  - Experimental laboratory study was made to test the knot integrity of identical,
      non-identical and parallel sliding knots, with three and five throws, made with
      synthetic resorbable multifilament suture materials. The knots were made with
      Novosyn (polyglactin 612), Safil (polyglycolic acid), Vicryl (polyglactin 612)
      and Vicryl plus (polyglactin 910 + triclosan), all with suture size: 3-0 USP. Per
      material 10 knots for every kind of knot were tested in a tensiometer, resulting
      in a total of 240 tests. Sliding knots with three throws were compared with the
      five throw sliding knots, and a comparison of the loop-holding capacities (LHC)
      of the different suture materials was made. Differences in suture material, knot
      type, and number of throws in the knot had a remarkable effect on knot
      performance. Adding two extra throws to a three throw non-identical or parallel
      sliding knot resulted in significantly more reliable knots (P < 0.05). In
      identical sliding knots, this effect was not seen, but these knots showed low
      LHCs, indicating poor knot reliability. Compared to the other suture materials,
      Safil showed significantly lower LHCs. Most of the mean LHCs of the various knots
      with Vicryl, Vicryl Plus or Novosyn were not statistically different from each
      other. Identical sliding knots appeared to be very unreliable, especially when
      made with three throws. Non-identical and parallel slipknots with five throws
      demonstrated superior knot integrity compared with the same knot types with three
      throws. Safil had inferior knot properties as compared to the other materials,
      but Vicryl, Vicryl Plus and Novosyn behaved virtually the same. The type of knot
      and the use of different suture materials have important influence on the
      integrity of the knot. A high knot reliability is nowadays all the more important
      because of the frequent use of resorbable suture materials. The suture gradually
      loses strength during the resorption process, so that an extra margin of safety
      neutralizes the effect of this process.

PMID- 23144643
TI  - A 4-cm G2 cervical submucosal myoma removed with the IBS(r) Integrated Bigatti
      Shaver.

PMID- 23144644
TI  - "Adhesions after abdominal, pelvic and intra-uterine surgery and their
      prevention"
AB  - We here present the full text of a patient leaflet we have designed, and
      routinely use, to provide preoperative education about adhesions to patients
      undergoing open or laparoscopic gynaecological surgery. The leaflet presents
      appropriate, patient-orientated information on the nature of adhesions, their
      causes and the health risks they may involve as well as on adhesiolysis and
      modern methods of adhesion prevention. As adhesion formation is not specific to
      gynaecological surgery, the leaflet can also be adapted for the purposes of
      general abdominal surgery.

PMID- 23144645
TI  - NMDA receptor signaling: death or survival?
AB  - Glutamate-induced neuronal damage is mainly caused by overactivation of N-methyl
      D-aspartate (NMDA) receptors. Conversely, normal physiological brain function and
      neuronal survival require adequate activation of NMDA receptors. Studies have
      revealed that NMDA receptor-induced neuronal death or survival is mediated
      through distinct subset of NMDA receptors triggering different intracellular
      signaling pathways. Here we discuss recent advances in the characterization of
      NMDA receptors in neuronal protection, emphasizing subunit-specific role, which
      contributes to temporal-spatial distribution, subcellular localization and
      diverse channel properties of NMDA receptors.

PMID- 23144646
TI  - GPCRs as potential therapeutic targets in preeclampsia.
AB  - Preeclampsia is an important obstetric complication that arises in 5% of women
      after the 20(th) week of gestation, for which there is no specific therapy and no
      cure. Although much of the recent investigation in this field has focused on
      soluble forms of the angiogenic membrane receptor tyrosine kinase Flt1 and the
      transforming growth factor beta co-receptor Endoglin, there is significant
      clinical potential for several GPCR targets and their agonists or antagonists in
      preeclampsia. In this review, we discuss several of the most promising candidates
      in this category, including calcitonin receptor-like receptor / receptor activity
      modifying protein 1 complexes, the angiotensin AT1, 2 and Mas receptors, and the
      relaxin receptor RXFP1. We also address some of the controversies surrounding the
      roles and therapeutic potential of these GPCRs and their (ant)agonists in
      preeclampsia.

PMID- 23144649
TI  - Ionic strength dependence of polyelectrolyte brush thickness.
AB  - Intramolecular repulsion between charged monomers imposes intrinsic tension in
      polyion, modifies its elasticity, and changes the dependence of polyelectrolyte
      brush thickness on salt concentration. We demonstrate that intrinsic polyion
      tension gives rise to a plateau of the brush thickness in the middle of salt
      dominated regime and to a subsequent steeper brush contraction with increasing
      salt concentration.

PMID- 23144647
TI  - Neurobehavioral risk is associated with gestational exposure to stress hormones.
AB  - The developmental origins of disease or fetal programming model predict that
      early exposures to threat or adverse conditions have lifelong consequences that
      result in harmful outcomes for health. The maternal endocrine 'fight or flight'
      system is a source of programming information for the human fetus to detect
      threats and adjust their developmental trajectory for survival. Fetal exposures
      to intrauterine conditions including elevated stress hormones increase the risk
      for a spectrum of health outcomes depending on the timing of exposure, the
      timetable of organogenesis and the developmental milestones assessed. Recent
      prospective studies, reviewed here, have documented the neurodevelopmental
      consequences of fetal exposures to the trajectory of stress hormones over the
      course of gestation. These studies have shown that fetal exposures to biological
      markers of adversity have significant and largely negative consequences for
      fetal, infant and child emotional and cognitive regulation and reduced volume in
      specific brain structures.

PMID- 23144648
TI  - Calcium regulation of keratinocyte differentiation.
AB  - Calcium is the major regulator of keratinocyte differentiation in vivo and in
      vitro. A calcium gradient within the epidermis promotes the sequential
      differentiation of keratinocytes as they traverse the different layers of the
      epidermis to form the permeability barrier of the stratum corneum. Calcium
      promotes differentiation by both outside-in and inside-out signaling. A number of
      signaling pathways involved with differentiation are regulated by calcium,
      including the formation of desmosomes, adherens junctions and tight junctions,
      which maintain cell-cell adhesion and play an important intracellular signaling
      role through their activation of various kinases and phospholipases that produce
      second messengers that regulate intracellular free calcium and PKC activity,
      critical for the differentiation process. The calcium receptor plays a central
      role by initiating the intracellular signaling events that drive differentiation
      in response to extracellular calcium. This review will discuss these mechanisms.

PMID- 23144650
TI  - Architectural layer-by-layer assembly of drug nanocapsules with PEGylated
      polyelectrolytes.
AB  - 150-200 nm diameter capsules containing 60-70 wt % of poorly soluble drugs,
      paclitaxel and camptothecin, were produced by layer-by-layer (LbL) assembly on
      drug nanocores in a solution containing uncharged stabilizers. Optimization of
      capsule shell architecture and thickness allowed for concentrated (3-5 mg/mL)
      colloids that are stable in isotonic salt buffers. Nanoparticle aggregation
      during the washless LbL-assembly was prevented by using low molecular weight
      block-copolymers of poly(amino acids) (poly-L-lysine and poly-L-glutamic acid)
      with polyethylene glycol (PEG) in combination with heparin and bovine serum
      albumin at every bilayer building step. Minimal amounts of the polyelectrolytes
      were used to recharge the surface of nanoparticles in this non-washing LbL
      process. Such PEGylated shells resulted in drug nanocapsules with high colloidal
      stability in PBS buffer and increased protein adhesion resistance. The washless
      LbL polyelectrolyte nanocapsule assembly process, colloidal stability and
      nanoparticle morphology were monitored by dynamic light scattering and
      electrophoretic mobility measurements, UV-vis spectroscopy, TEM, SEM and laser
      confocal microscopy imaging.

PMID- 23144652
TI  - Molecular imaging true-colour spectroscopic optical coherence tomography.
AB  - Molecular imaging holds a pivotal role in medicine due to its ability to provide
      invaluable insight into disease mechanisms at molecular and cellular levels. To
      this end, various techniques have been developed for molecular imaging, each with
      its own advantages and disadvantages(1-4). For example, fluorescence imaging
      achieves micrometre-scale resolution, but has low penetration depths and is
      mostly limited to exogenous agents. Here, we demonstrate molecular imaging of
      endogenous and exogenous chromophores using a novel form of spectroscopic optical
      coherence tomography. Our approach consists of using a wide spectral bandwidth
      laser source centred in the visible spectrum, thereby allowing facile assessment
      of haemoglobin oxygen levels, providing contrast from readily available
      absorbers, and enabling true-colour representation of samples. This approach
      provides high spectral fidelity while imaging at the micrometre scale in three
      dimensions. Molecular imaging true-colour spectroscopic optical coherence
      tomography (METRiCS OCT) has significant implications for many biomedical
      applications including ophthalmology, early cancer detection, and understanding
      fundamental disease mechanisms such as hypoxia and angiogenesis.

PMID- 23144653
TI  - The response of correlated traits following cessation of fishery-induced
      selection.
AB  - The application of evolutionary principles to the management of fisheries has
      gained considerable attention recently. Harvesting of fish may apply directional
      or disruptive selection to key life-history traits, and evidence for fishery
      induced evolution is growing. The traits that are directly selected upon are
      often correlated (genetically or phenotypically) with a suite of interrelated
      physiological, behavioral, and morphological characters. A question that has
      received comparatively little attention is whether or not, after cessation of
      fishery-induced selection, these correlated traits revert back to previous
      states. Here, we empirically examine this question. In experiments with the
      Atlantic silverside, Menidia menidia, we applied size-selective culling for five
      generations and then maintained the lines a further five generations under random
      harvesting. We found that some traits do return to preharvesting levels (e.g.,
      larval viability), some partially recover (e.g., egg volume, size-at-hatch), and
      others show no sign of change (e.g., food consumption rate, vertebral number).
      Such correlations among characters could, in theory, greatly accelerate or
      decelerate the recovery of fish populations. These results may explain why some
      fish stocks fail to recover after fishing pressure is relaxed.

PMID- 23144651
TI  - "Shift-and-Persist" Strategies: Why Low Socioeconomic Status Isn't Always Bad for
      Health.
AB  - Some individuals, despite facing recurrent, severe adversities in life such as
      low socioeconomic status (SES), are nonetheless able to maintain good physical
      health. This article explores why these individuals deviate from the expected
      association of low SES and poor health and outlines a "shift-and-persist" model
      to explain the psychobiological mechanisms involved. This model proposes that, in
      the midst of adversity, some children find role models who teach them to trust
      others, better regulate their emotions, and focus on their futures. Over a
      lifetime, these low-SES children develop an approach to life that prioritizes
      shifting oneself (accepting stress for what it is and adapting the self through
      reappraisals) in combination with persisting (enduring life with strength by
      holding on to meaning and optimism). This combination of shift-and-persist
      strategies mitigates sympathetic-nervous-system and hypothalamic-pituitary
      adrenocortical responses to the barrage of stressors that low-SES individuals
      confront. This tendency vectors individuals off the trajectory to chronic disease
      by forestalling pathogenic sequelae of stress reactivity, like insulin
      resistance, high blood pressure, and systemic inflammation. We outline evidence
      for the model and argue that efforts to identify resilience-promoting processes
      are important in this economic climate, given limited resources for improving the
      financial circumstances of disadvantaged individuals. 

PMID- 23144654
TI  - Gene flow networks among American Aedes aegypti populations.
AB  - The mosquito Aedes aegypti, the dengue virus vector, has spread throughout the
      tropics in historical times. While this suggests man-mediated dispersal,
      estimating contemporary connectivity among populations has remained elusive.
      Here, we use a large mtDNA dataset and a Bayesian coalescent framework to test a
      set of hypotheses about gene flow among American Ae. aegypti populations. We
      assessed gene flow patterns at the continental and subregional (Amazon basin)
      scales. For the Americas, our data favor a stepping-stone model in which gene
      flow is higher among adjacent populations but in which, at the same time, North
      American and southeastern Brazilian populations are directly connected, likely
      via sea trade. Within Amazonia, the model with highest support suggests extensive
      gene flow among major cities; Manaus, located at the center of the subregional
      transport network, emerges as a potentially important connecting hub. Our results
      suggest substantial connectivity across Ae. aegypti populations in the Americas.
      As long-distance active dispersal has not been observed in this species, our data
      support man-mediated dispersal as a major determinant of the genetic structure of
      American Ae. aegypti populations. The inferred topology of interpopulation
      connectivity can inform network models of Ae. aegypti and dengue spread.

PMID- 23144655
TI  - Life history change in response to fishing and an introduced predator in the East
      African cyprinid Rastrineobola argentea.
AB  - Fishing and introduced species are among the most important stressors affecting
      freshwaters and can also be strong selective agents. We examined the combined
      effects of commercial fishing and an introduced predator (Nile perch, Lates
      niloticus) on life history traits in an African cyprinid fish (Rastrineobola
      argentea) native to the Lake Victoria basin in East Africa. To understand whether
      these two stressors have driven shifts in life history traits of R. argentea, we
      tested for associations between life history phenotypes and the presence/absence
      of stressors both spatially (across 10 Ugandan lakes) and temporally (over four
      decades in Lake Victoria). Overall, introduced Nile perch and fishing tended to
      be associated with a suite of life history responses in R. argentea, including:
      decreased body size, maturation at smaller sizes, and increased reproductive
      effort (larger eggs; and higher relative fecundity, clutch volume, and ovary
      weight). This is one of the first well-documented examples of fisheries-induced
      phenotypic change in a tropical, freshwater stock; the magnitude of which raises
      some concerns for the long-term sustainability of this fishery, now the most
      important (by mass) in Lake Victoria.

PMID- 23144656
TI  - Evolution of pathogenicity traits in the apple scab fungal pathogen in response
      to the domestication of its host.
AB  - Understanding how pathogens emerge is essential to bring disease-causing agents
      under durable human control. Here, we used cross-pathogenicity tests to
      investigate the changes in life-history traits of the fungal pathogen Venturia
      inaequalis associated with host-tracking during the domestication of apple and
      subsequent host-range expansion on the wild European crabapple (Malus
      sylvestris). Pathogenicity of 40 isolates collected in wild and domesticated
      ecosystems was assessed on the domesticated apple, its Central Asian main
      progenitor (M. sieversii) and M. sylvestris. Isolates from wild habitats in the
      centre of origin of the crop were not pathogenic on the domesticated apple and
      less aggressive than other isolates on their host of origin. Isolates from the
      agro-ecosystem in Central Asia infected a higher proportion of plants with higher
      aggressiveness, on both the domesticated host and its progenitor. Isolates from
      the European crabapple were still able to cause disease on other species but were
      less aggressive and less frequently virulent on these hosts than their endemic
      populations. Our results suggest that the domestication of apple was associated
      with the acquisition of virulence in the pathogen following host-tracking. The
      spread of the disease in the agro-ecosystem would also have been accompanied by
      an increase in overall pathogenicity.

PMID- 23144657
TI  - Can interbreeding of wild and artificially propagated animals be prevented by
      using broodstock selected for a divergent life history?
AB  - TWO STRATEGIES HAVE BEEN PROPOSED TO AVOID NEGATIVE GENETIC EFFECTS OF
      ARTIFICIALLY PROPAGATED INDIVIDUALS ON WILD POPULATIONS: (i) integration of wild
      and captive populations to minimize domestication selection and (ii) segregation
      of released individuals from the wild population to minimize interbreeding. We
      tested the efficacy of the strategy of segregation by divergent life history in a
      steelhead trout, Oncorhynchus mykiss, system, where hatchery fish were selected
      to spawn months earlier than the indigenous wild population. The proportion of
      wild ancestry smolts and adults declined by 10-20% over the three generations
      since the hatchery program began. Up to 80% of the naturally produced steelhead
      in any given year were hatchery/wild hybrids. Regression model selection analysis
      showed that the proportion of hatchery ancestry smolts was lower in years when
      stream discharge was high, suggesting a negative effect of flow on reproductive
      success of early-spawning hatchery fish. Furthermore, proportions of hybrid
      smolts and adults were higher in years when the number of naturally spawning
      hatchery-produced adults was higher. Divergent life history failed to prevent
      interbreeding when physical isolation was ineffective, an inadequacy that is
      likely to prevail in many other situations.

PMID- 23144658
TI  - Human-impacted landscapes facilitate hybridization between a native and an
      introduced tree.
AB  - Spatial and temporal dynamics of hybridization, in particular the influence of
      local environmental conditions, are well studied for sympatric species but less
      is known for native-introduced systems, especially for long-lived species. We
      used microsatellite and chloroplast DNA markers to characterize the influence of
      anthropogenic landscapes on the extent, direction, and spatial distribution of
      hybridization between a native North American tree Juglans cinerea (butternut)
      and an introduced tree Juglans ailantifolia (Japanese walnut) for 1363 trees at
      48 locations across the native range of butternut. Remarkably, admixture in
      anthropogenic sites reached nearly 70%, while fragmented and continuous forests
      showed minimal admixture (<8%). Furthermore, more hybrids in anthropogenic sites
      had J. ailantifolia seed parents (95%) than hybrids in fragmented and continuous
      forests (69% and 59%, respectively). Our results show a strong influence of
      landscape type on rate and direction of realized gene flow. While hybrids are
      common in anthropogenic landscapes, our results suggest that even small forested
      landscapes serve as substantial barriers to hybrid establishment, a key
      consideration for butternut conservation planning, a species already exhibiting
      severe decline, and for other North American forest trees that hybridize with
      introduced congeners.

PMID- 23144659
TI  - Untangling the positive genetic correlation between rainbow trout growth and
      survival.
AB  - Explanations for positive and negative genetic correlations between growth and
      fitness traits are essential for life-history theory and selective breeding.
      Here, we test whether growth and survival display genetic trade-off. Furthermore,
      we assess the potential of third-party traits to explain observed genetic
      associations. First, we estimated genetic correlations of growth and survival of
      rainbow trout. We then explored whether these associations are explained by
      genetic correlations with health, body composition and maturity traits. Analysis
      included 14 traits across life stages and environments. Data were recorded from
      249 166 individuals belonging to 10 year classes of a pedigreed population. The
      results revealed that rapid growth during grow-out was genetically associated
      with enhanced survival (mean r(G) = 0.17). This resulted because genotypes with
      less nematode caused cataract grew faster and were more likely to survive.
      Fingerling survival was not genetically related to weight or to grow-out
      survival. Instead, rapid fingerling growth made fish prone to deformations (r(G)
      = 0.18). Evolutionary genetics provides a theoretical framework to study
      variation in genetic correlations. This study demonstrates that genetic
      correlation patterns of growth and survival can be explained by a set of key
      explanatory traits recorded at different life stages and that these traits can be
      simultaneously improved by selective breeding.

PMID- 23144660
TI  - Gentle Africanized bees on an oceanic island.
AB  - Oceanic islands have reduced resources and natural enemies and potentially affect
      life history traits of arriving organisms. Among the most spectacular invasions
      in the Western hemisphere is that of the Africanized honeybee. We hypothesized
      that in the oceanic island Puerto Rico, Africanized bees will exhibit differences
      from the mainland population such as for defensiveness and other linked traits.
      We evaluated the extent of Africanization through three typical Africanized
      traits: wing size, defensive behavior, and resistance to Varroa destructor mites.
      All sampled colonies were Africanized by maternal descent, with over 65% presence
      of European alleles at the S-3 nuclear locus. In two assays evaluating defense,
      Puerto Rican bees showed low defensiveness similar to European bees. In
      morphology and resistance to mites, Africanized bees from Puerto Rico are similar
      to other Africanized bees. In behavioral assays on mechanisms of resistance to
      Varroa, we directly observed that Puerto Rican Africanized bees groomed-off and
      bit the mites as been observed in other studies. In no other location,
      Africanized bees have reduced defensiveness while retaining typical traits such
      as wing size and mite resistance. This mosaic of traits that has resulted during
      the invasion of an oceanic island has implications for behavior, evolution, and
      agriculture.

PMID- 23144661
TI  - Drugs that target pathogen public goods are robust against evolved drug
      resistance.
AB  - Pathogen drug resistance is a central problem in medicine and public health. It
      arises through somatic evolution, by mutation and selection among pathogen cells
      within a host. Here, we examine the hypothesis that evolution of drug resistance
      could be reduced by developing drugs that target the secreted metabolites
      produced by pathogen cells instead of directly targeting the cells themselves.
      Using an agent-based computational model of an evolving population of pathogen
      cells, we test this hypothesis and find support for it. We also use our model to
      explain this effect within the framework of standard evolutionary theory. We find
      that in our model, the drugs most robust against evolved drug resistance are
      those that target the most widely shared external products, or 'public goods', of
      pathogen cells. We also show that these drugs exert a weak selective pressure for
      resistance because they create only a weak correlation between drug resistance
      and cell fitness. The same principles apply to design of vaccines that are robust
      against vaccine escape. Because our theoretical results have crucial practical
      implications, they should be tested by empirical experiments.

PMID- 23144662
TI  - Contrasting patterns of nucleotide diversity for four conifers of Alpine European
      forests.
AB  - A candidate gene approach was used to identify levels of nucleotide diversity and
      to identify genes departing from neutral expectations in coniferous species of
      the Alpine European forest. Twelve samples were collected from four species that
      dominate montane and subalpine forests throughout Europe: Abies alba Mill, Larix
      decidua Mill, Pinus cembra L., and Pinus mugo Turra. A total of 800 genes,
      originally resequenced in Pinus taeda L., were resequenced across 12 independent
      trees for each of the four species. Genes were assigned to two categories,
      candidate and control, defined through homology-based searches to Arabidopsis.
      Estimates of nucleotide diversity per site varied greatly between polymorphic
      candidate genes (range: 0.0004-0.1295) and among species (range: 0.0024-0.0082),
      but were within the previously established ranges for conifers. Tests of
      neutrality using stringent significance thresholds, performed under the standard
      neutral model, revealed one to seven outlier loci for each species. Some of these
      outliers encode proteins that are involved with plant stress responses and form
      the basis for further evolutionary enquiries.

PMID- 23144663
TI  - Intravascular multispectral optoacoustic tomography of atherosclerosis: prospects
      and challenges.
AB  - The progression of atherosclerosis involves complex changes in the structure,
      composition and biology of the artery wall. Currently, only anatomical plaque
      burden is routinely characterized in living patients, whereas compositional and
      biological changes are mostly inaccessible. However, anatomical imaging alone has
      proven to be insufficient for accurate diagnostics of the disease. Multispectral
      optoacoustic tomography offers complementary data to anatomical methods and is
      capable of imaging both tissue composition and, via the use of molecular markers,
      the biological activity therein. In this paper we review recent progress in
      multispectral optoacoustic tomography imaging of atherosclerosis with specific
      emphasis on intravascular applications. The potential capabilities of
      multispectral optoacoustic tomography are compared with those of established
      intravascular imaging techniques and current challenges on the road towards a
      clinically viable imaging modality are discussed.

PMID- 23144665
TI  - Reliability of accelerometric measurement of physical activity in older adults
      the benefit of using the trimmed sum.
AB  - There is general consensus that physical activity is important for preserving
      functional capacities of older adults and positively influencing quality of life.
      While accelerometry is widely accepted and applied to assess physical activity in
      studies, several problems with this method remain (e.g., low retest reliability,
      measurement errors). The aim of this study was to test the intra-instrumental
      retest reliability of a wrist-worn accelerometer in a 3-day measurement of
      physical activity in older adults and to compare different estimators. A sample
      of 123 older adults (76.5 +/- 5.1 years, 59 % female) wore a uniaxial
      accelerometer continuously for 1 week. The data were split into two repeated
      measurement values (week set) of 3 days each. The sum, the 80-99th quantiles and
      the 80-99th trimmed sums were built for each week set. Retest reliability was
      assessed for each estimator and graphically demonstrated by Bland-Altman plots.
      The intraclass correlation of the retest reliability ranged from 0.22 to 0.91.
      Retest reliability increases when a more robust estimator than the overall sum is
      used. Therefore, the trimmed sum can be recommended as a conservative estimate of
      the physical activity level of older adults.

PMID- 23144664
TI  - Repetition Priming and Repetition Suppression: A Case for Enhanced Efficiency
      Through Neural Synchronization.
AB  - Stimulus repetition in identification tasks leads to improved behavioral
      performance ("repetition priming") but attenuated neural responses ("repetition
      suppression") throughout task-engaged cortical regions. While it's clear that
      this pervasive brain-behavior relationship reflects some form of improved
      processing efficiency, the exact form that it takes remains elusive. In this
      Discussion Paper, we review four different theoretical proposals that have the
      potential to link repetition suppression and priming, with a particular focus on
      a proposal that stimulus repetition affects improved efficiency through enhanced
      neural synchronization. We argue that despite exciting recent work on the role of
      neural synchronization in cognitive processes such as attention and perception,
      similar studies in the domain of learning and memory - and priming, in particular
      - have been lacking. We emphasize the need for new studies with adequate
      spatiotemporal resolution, formulate several novel predictions, and discuss our
      ongoing efforts to disentangle the current proposals.

PMID- 23144666
TI  - Psychoemotional features of a doubtful disorder: functional dyspepsia.
AB  - OBJECTIVE: To delineate the psychological profile of individuals prone to FD-like
      symptoms (FDLS). METHOD: A triple questionnaire of 614 items (including
      psychological and medical ones) was given to 10192 respondents, the results were
      analyzed by means of Cronbach alpha, and Chi square test, together with an ad-hoc
      designed method that implied ranking and outliers detecting. RESULTS AND
      CONCLUSIONS: FDLS appears to be an accompanying feature of many (if not most)
      human emotions and are more frequent in anxious, timid, pessimistic, discontent,
      irascible, tense, success-doubting, unexpected-dreading individuals, bothered by
      persistent thoughts and tormented by the professional requirements and the lack
      of time. A higher degree of specificity might have: chiefly fear of failure,
      susceptibility, and tension, secondarily emotivity, fear of unpredictable events,
      sense of insufficient time, preoccupation with authority factors, and tendency to
      endure unacceptable situations, and also faulty patience and lack of punctuality.
      Rumination appears to be the psychological tendency most strongly associated with
      FD. Nocturnal epigastric pain seems to indicate a submissive nature but a rather
      responsibilities-free childhood, while early satiety is associated with
      inclination to work and responsibility and preoccupation with self-image. The
      superposition of FD symptoms with biliary and esophageal symptoms cast a doubt
      over the distinctness and even the materiality of the various functional
      digestive disorders.

PMID- 23144667
TI  - Surgical treatment of colon cancer: Colentina surgical clinic experience.
AB  - Most patients with colon cancer are surgically treated, with postoperative
      association of chemotherapy and possibly immunotherapy in advanced cases.
      Surgical treatment is chosen depending on the evolution stage, tumor topography
      and the existence of complications, colonic surgery being dictated by colonic
      vascularization. The radical character of the surgical intervention can be
      assured only in the early stages of the tumor. Colostomy is rarely necessary in
      patients with colon cancer. In the period of the last 5 years (2007-2011), 307
      patients with colon cancer were operated in "Colentina" Surgical Clinic, radical
      intervention being possible only in 219 cases. 48 cases were emergency
      interventions for occlusion or perforation with peritonitis. Every time the
      mechanical preparation of the bowel was not possible, the intraoperative washout
      technique was used. Postoperative complications were met in 27 cases, being
      represented by bleeding (3 cases), peritoneal abscess (5 cases), anastomotic
      fistula (7 cases), abdominal wound infection (12 cases). In 5 cases the operation
      was done laparoscopically. Preoperative mortality was of 13 cases. Postoperative
      chemotherapy was done in the great majority of cases.

PMID- 23144668
TI  - Embodied artificial evolution: Artificial evolutionary systems in the 21st
      Century.
AB  - Evolution is one of the major omnipresent powers in the universe that has been
      studied for about two centuries. Recent scientific and technical developments
      make it possible to make the transition from passively understanding to actively
      using evolutionary processes. Today this is possible in Evolutionary Computing,
      where human experimenters can design and manipulate all components of
      evolutionary processes in digital spaces. We argue that in the near future it
      will be possible to implement artificial evolutionary processes outside such
      imaginary spaces and make them physically embodied. In other words, we envision
      the "Evolution of Things", rather than just the evolution of digital objects,
      leading to a new field of Embodied Artificial Evolution (EAE). The main objective
      of this paper is to present a unifying vision in order to aid the development of
      this high potential research area. To this end, we introduce the notion of EAE,
      discuss a few examples and applications, and elaborate on the expected benefits
      as well as the grand challenges this developing field will have to address.

PMID- 23144669
TI  - Perceptions of HIV transmission risk in commercial and public sex venues.
AB  - BACKGROUND: Sexual behaviors of men who have sex with men (MSM) that occur in
      sexually charged venues (e.g., bathhouse, sex club, public park) are a target for
      research and intervention due to concerns about the role these venues may have in
      the transmission of HIV and other sexually transmitted infections (STIs).
      However, these efforts often exclude how individuals perceive HIV risk in terms
      of sex venue use. This paper analyzes how venue-specific perceptions of HIV
      transmission risk differ across venues and by onsite sexual behavior.  METHOD:
      Cross-sectional data collected using an Internet survey completed by 139 MSM who
      attended at least one sex venue (e.g., bathhouse, sex club, gym/health club,
      public park) in the past month.  RESULTS: Risk perceptions were highest for
      bathhouses and sex clubs, though no significant differences were detected between
      any of the venues. With few exceptions, men who reported not engaging in sex or
      low-risk behaviors (i.e., masturbation or mutual masturbation) during venue
      attendance perceived higher risks than those who engaged in high-risk behaviors
      (i.e., anal sex). Interestingly, risk perceptions of public bathrooms, parks, and
      video/buddy booths were lower for attendees who reported unprotected oral sex
      with ejaculation than men who reported safer or riskier behaviors.  CONCLUSION:
      These findings provide important insights into how MSM perceive HIV risk in sex
      venues and highlight a need for expanded outreach and education in locations
      where sexual risk taking may be underestimated.

PMID- 23144670
TI  - Food Systems and Public Health: Linkages to Achieve Healthier Diets and Healthier
      Communities.
AB  - The Airlie Conference on "Food Systems and Public Health: Linkages to Achieve
      Healthier Diets and Healthier Communities" was convened to discuss how we as a
      nation can shift toward promoting healthy, sustainably produced foods that are
      aligned with national dietary and health priorities; the most strategic changes
      in policy, governance and practices that can help this shift occur; and identify
      knowledge gaps and policy-relevant research needs. This special theme issue
      presents papers emanating from the conference, and policy-relevant research and
      action recommendations from the small group breakout sessions.

PMID- 23144671
TI  - Aligning Food Systems Policies to Advance Public Health.
AB  - The involvement of public health professionals in food and agricultural policy
      provides tremendous opportunities for advancing the public's health. It is
      particularly challenging, however, for professionals to understand and consider
      the numerous policy drivers that impact the food system, which range from
      agricultural commodity policies to local food safety ordinances. Confronted with
      this complexity in the food system, policy advocates often focus on narrow
      objectives with disregard for the larger system. This commentary contends that,
      in order to be most effective, public health professionals need to consider the
      full range of interdependent policies that affect the system. Food policy
      councils have proven to be an effective tool, particularly at the local and state
      level, for developing comprehensive food systems policies that can improve public
      health.

PMID- 23144672
TI  - Principles for Framing a Healthy Food System.
AB  - Wicked problems are most simply defined as ones that are impossible to solve. In
      other words, the range of complex interacting influences and effects; the
      influence of human values in all their range; and the constantly changing
      conditions in which the problem exists guarantee that what we strive to do is
      improve the situation rather than solve the wicked problem. This does not mean
      that we cannot move a long way toward resolving the problem but simply that there
      is no clean endpoint. This commentary outlines principles that could be used in
      moving us toward a healthy food system within the framework of it presenting as a
      wicked problem.

PMID- 23144673
TI  - Reshaping the Food System for Ecological Public Health.
AB  - Twenty-first-century food policy will have to address a new set of fundamentals.
      Some are relatively new such as climate change and peak oil, and some merely new
      versions of very old ones such as water, population, land pressures, labor, and
      urbanisation. Policy-makers now need radically to alter the policy mix inherited
      from the last major policy reconfiguration in the mid-20th century. Then the
      demon was supply, and poor health was mainly due to underconsumption and poverty.
      The policy solution was to raise output and reduce prices. Today the challenge is
      more complex, a coexistence of over-, under-, and malconsumption alongside
      continuing gross inequalities within and between nations. The article proposes
      that a new paradigm is emerging, termed here ecological public health, which sees
      human and planetary health as linked and food as a key connection point. The
      article outlines aspects of what this entails, stressing the need for food policy
      to address not just supply but governance and consumer cultural challenges too.
      Seven priorities are proposed for policy-makers.

PMID- 23144674
TI  - Identifying Innovative Interventions to Promote Healthy Eating Using Consumption
      Oriented Food Supply Chain Analysis.
AB  - The mapping and analysis of supply chains is a technique increasingly used to
      address problems in the food system. Yet such supply chain management has not yet
      been applied as a means of encouraging healthier diets. Moreover, most policies
      recommended to promote healthy eating focus on the consumer end of the chain.
      This article proposes a consumption-oriented food supply chain analysis to
      identify the changes needed in the food supply chain to create a healthier food
      environment, measured in terms of food availability, prices, and marketing. Along
      with established forms of supply chain analysis, the method is informed by a
      historical overview of how food supply chains have changed over time. The method
      posits that the actors and actions in the chain are affected by organizational,
      financial, technological, and policy incentives and disincentives, which can in
      turn be levered for change. It presents a preliminary example of the supply of
      Coca-Cola beverages into school vending machines and identifies further potential
      applications. These include fruit and vegetable supply chains, local food chains,
      supply chains for health-promoting versions of food products, and identifying
      financial incentives in supply chains for healthier eating.

PMID- 23144675
TI  - US-Based Food and Agricultural Value Chains and Their Relevance to Healthy Diets.
AB  - This article examines the structure and health implications of two industries,
      chicken and tomatoes, that play prominent roles in US food and agricultural
      competitiveness. Both industries have become more concentrated over time, with
      powerful "lead firms" driving geographical, technological, and marketing changes.
      Overall, a processed food revolution has taken place in agricultural products
      that transforms the types of food and dietary options available to consumers. The
      nature of contemporary food and agricultural value chains affects the strategies
      and policies that can be effectively employed to address major health goals such
      as improved nutrition, food safety, and food security.

PMID- 23144676
TI  - Economies of Size in Production Agriculture.
AB  - Economies of size refer to the ability of a farm to lower costs of production by
      increasing production. Agriculture production displays an L-shaped average cost
      curve where costs are lower initially but reach a point where no further gains
      are achieved. Spreading fixed costs, bulk purchases, and marketing power are
      cited as reasons for economies of size. Labor-reducing technologies may be the
      primary reason. Most studies do not include the external costs from prophylactic
      antibiotic use, impact on rural communities, and environmental damage associated
      with large-scale production. These can contribute to the economies of size.

PMID- 23144677
TI  - Agriculture Policy Is Health Policy.
AB  - The Farm Bill is meant to supplement and secure farm incomes, ensure a stable
      food supply, and support the American farm economy. Over time, however, it has
      evolved into a system that creates substantial health impacts, both directly and
      indirectly. By generating more profit for food producers and less for family
      farmers; by effectively subsidizing the production of lower-cost fats, sugars,
      and oils that intensify the health-destroying obesity epidemic; by amplifying
      environmentally destructive agricultural practices that impact air, water, and
      other resources, the Farm Bill influences the health of Americans more than is
      immediately apparent. In this article, we outline three major public health
      issues influenced by American farm policy. These are (1) rising obesity; (2) food
      safety; and (3) environmental health impacts, especially exposure to toxic
      substances and pesticides.

PMID- 23144678
TI  - A New Health Care Prevention Agenda: Sustainable Food Procurement and
      Agricultural Policy.
AB  - Health care leaders are broadening their awareness to include the need to address
      the food system as a means to individual, public, and global health, above and
      beyond basic nutritional factors. Key voices from the health care sector have
      begun to engage in market transformation and are aggregating to articulate the
      urgency for engagement in food and agricultural policy. Systemic transformation
      requires a range of policies that complement one another and address various
      aspects of the food system. Health care involvement in policy and advocacy is
      vital to solve the expanding ecological health crises facing our nation and globe
      and will require an urgency that may be unprecedented.

PMID- 23144679
TI  - Recipe for a Better Tomorrow: A Food Industry Perspective on Sustainability and
      Our Food System.
AB  - The food and agriculture sector is central to efforts to improve public health
      today and protect and restore natural systems necessary to support good health in
      the future. The sector has a greater direct impact on land and water resources,
      employment, and economic activity than any other. And, from a finite resource
      base, it is underpinning not only food and fiber production but is increasingly
      relied upon to provide the raw materials for energy, building materials,
      packaging, and nonfood consumable products. This commentary reviews consumer
      attitudes and the transformational changes required in the food and agriculture
      sector to meet today's needs and ensure a better tomorrow.

PMID- 23144681
TI  - Conference Agenda: Food Systems and Public Health Conference: Linkages to Achieve
      Healthier Diets and Healthier Communities.

PMID- 23144680
TI  - Research and Action Priorities for Linking Public Health, Food Systems, and
      Sustainable Agriculture: Recommendations from the Airlie Conference.
AB  - One hundred leading researchers, practitioners, and advocates in public health,
      health care, nutrition, obesity, economics, sustainable agriculture, and food
      systems met at the Airlie Conference Center in April 2009 to discuss creating
      linkages among food systems, public health, and sustainable agriculture in order
      to achieve healthier diets, healthier communities, and a healthier planet.
      Participants convened in small groups to explore and discuss research that is
      needed to create a health-based and sustainable food system. The discussion and
      key recommendations from the small breakout sessions are presented.

PMID- 23144682
TI  - Food Systems and Public Health Conference: Linkages to Achieve Healthier Diets
      and Healthier Communities: Airlie Conference Center April 1-3, 2009.

PMID- 23144683
TI  - Internet Resources.

PMID- 23144690
TI  - Time-dependent stabilization of hypoxia inducible factor-1alpha by different
      intracellular sources of reactive oxygen species.
AB  - Intratumoral hypoxia is a major obstacle in the development of effective cancer
      chemotherapy, decreasing the efficacy of anti-neoplastic drugs in several solid
      tumours. The hypoxic environment, through its master regulator hypoxia inducible
      factor-1 (HIF-1), is able to maintain an anti-apoptotic potential through
      activation of critical genes associated with drug resistance. Besides affecting
      metabolism and motility of tumour cells, hypoxia also paradoxically increases
      production of reactive oxygen species (ROS), which contribute to stabilize HIF-1
      through a redox-mediated inhibition of its proteolysis. Here we reported that 1%
      O(2) hypoxia increases the resistance of human metastatic melanoma cells to
      conventional chemotherapy with etoposide, and that the increase in
      chemoresistance strongly depends on ROS delivery due to hypoxia. We reported a
      biphasic redox-dependent role of HIF-1, involving mitochondrial complex III and
      NADPH oxidase as oxidants sources, synergising in enhancing survival to
      chemotherapy. The feed-forward loop engaged by hypoxia involves first an HIF-1
      dependent vascular endothelial growth factor-A (VEGF-A) autocrine production and,
      in the later phase, activation of NADPH oxidase from VEGF/VEGFR2 interaction,
      finally leading to a further redox-dependent long lasting stabilization of HIF-1.
      We therefore identified a redox-dependent circuitry linking hypoxia-driven ROS to
      VEGF-A secretion and to enhanced melanoma cell survival to etoposide
      chemotherapy.

PMID- 23144691
TI  - MicroRNA-149 inhibits proliferation and cell cycle progression through the
      targeting of ZBTB2 in human gastric cancer.
AB  - An increasing body of evidence indicates that miR-149 can both suppress and
      promote tumor growth depending on the tumor type. However, the role of miR-149 in
      the progression of gastric cancer (GC) remains unknown. Here we report that miR
      149 is a tumor suppressor in human gastric cancer. miR-149 expression is
      decreased in GC cell lines and clinical specimens in comparison to normal gastric
      epithelial cell and tissues, respectively. The expression levels of miR-149 also
      correlate with the differentiation degree of GC cells and tissues. Moreover,
      ectopic expression of miR-149 in gastric cancer cells inhibits proliferation and
      cell cycle progression by down-regulating ZBTB2, a potent repressor of the ARF
      HDM2-p53-p21 pathway, with a potential binding site for miR-149 in its mRNA's
      3'UTR. It is also found that ZBTB2 expression increases in GC cells and tissues
      compared to normal gastric epithelial cell and tissues, respectively. Silencing
      of ZBTB2 leads to suppression of cell growth and cell cycle arrest in G0/G1
      phase, indicating that ZBTB2 may act as an oncogene in GC. Furthermore,
      transfection of miR-149 mimics into gastric cancer cells induces down-regulation
      of ZBTB2 and HDM2, and up-regulation of ARF, p53, and p21 compared to the
      controls. In summary, our data suggest that miR-149 functions as a tumor
      suppressor in human gastric cancer by, at least partially through, targeting
      ZBTB2.

PMID- 23144692
TI  - Multiple analyses of G-protein coupled receptor (GPCR) expression in the
      development of gefitinib-resistance in transforming non-small-cell lung cancer.
AB  - There is increasing evidence that functional crosstalk between GPCRs and EGFR
      contributes to the progression of colon, lung, breast, ovarian, prostate and head
      and neck tumors. In this study, we performed multiple analyses of GPCR expression
      in a gefitinib-resistant non-small cell lung cancer (NSCLC) cell line, H1975,
      which harbors an L858R/T790M mutation. To determine the expression profile of
      mRNAs encoding 384 GPCRs in normal human lung fibroblast (NHLF) and H1975 cells,
      a GPCR-specific microarray analysis was performed. A heat-map of the microarray
      revealed considerable differences in the expression of GPCRs between NHLF and
      H1975 cells. From the GPCR expression list, we selected some GPCR
      agonists/antagonist to investigate whether the respective ligands could affect
      the growth of H1975 cells. Among them, treatment with either a selective
      antagonist of adenosine A2a receptors, which were highly expressed in H1975 cell
      and another gefitinib-resistant NSCLC cells, HCC827GR cells or "small interfering
      RNA" (siRNA) targeting adenosine A2a receptors produced a significant decrease in
      cell viability of both H1975 and HCC827GR cells. Among up-regulated GPCRs in
      H1975 cells, Gs-, Gi- and Gq-coupled GPCRs were expressed almost equally. Among
      down-regulated GPCRs, Gi-coupled GPCRs were dominantly expressed in H1975 cells.
      The present results suggest that multilayered crosstalk between GPCRs and EGFR
      may play an important role in orchestrating downstream signaling molecules that
      are implicated in the development of gefitinib-resistant NSCLC.

PMID- 23144693
TI  - Sensitivity analysis of an individual-based model for simulation of influenza
      epidemics.
AB  - Individual-based epidemiology models are increasingly used in the study of
      influenza epidemics. Several studies on influenza dynamics and evaluation of
      intervention measures have used the same incubation and infectious period
      distribution parameters based on the natural history of influenza. A sensitivity
      analysis evaluating the influence of slight changes to these parameters (in
      addition to the transmissibility) would be useful for future studies and real
      time modeling during an influenza pandemic.In this study, we examined individual
      and joint effects of parameters and ranked parameters based on their influence on
      the dynamics of simulated epidemics. We also compared the sensitivity of the
      model across synthetic social networks for Montgomery County in Virginia and New
      York City (and surrounding metropolitan regions) with demographic and rural-urban
      differences. In addition, we studied the effects of changing the mean infectious
      period on age-specific epidemics. The research was performed from a public health
      standpoint using three relevant measures: time to peak, peak infected proportion
      and total attack rate. We also used statistical methods in the design and
      analysis of the experiments. The results showed that: (i) minute changes in the
      transmissibility and mean infectious period significantly influenced the attack
      rate; (ii) the mean of the incubation period distribution appeared to be
      sufficient for determining its effects on the dynamics of epidemics; (iii) the
      infectious period distribution had the strongest influence on the structure of
      the epidemic curves; (iv) the sensitivity of the individual-based model was
      consistent across social networks investigated in this study and (v) age-specific
      epidemics were sensitive to changes in the mean infectious period irrespective of
      the susceptibility of the other age groups. These findings suggest that small
      changes in some of the disease model parameters can significantly influence the
      uncertainty observed in real-time forecasting and predicting of the
      characteristics of an epidemic.

PMID- 23144694
TI  - Deformation of the Durom acetabular component and its impact on tribology in a
      cadaveric model--a simulator study.
AB  - BACKGROUND: Recent studies have shown that the acetabular component frequently
      becomes deformed during press-fit insertion. The aim of this study was to explore
      the deformation of the Durom cup after implantation and to clarify the impact of
      deformation on wear and ion release of the Durom large head metal-on-metal (MOM)
      total hips in simulators. METHODS: Six Durom cups impacted into reamed acetabula
      of fresh cadavers were used as the experimental group and another 6 size-paired
      intact Durom cups constituted the control group. All 12 Durom MOM total hips were
      put through a 3 million cycle (MC) wear test in simulators. RESULTS: The 6 cups
      in the experimental group were all deformed, with a mean deformation of 41.78 +/-
      8.86 um. The average volumetric wear rate in the experimental group and in the
      control group in the first million cycle was 6.65 +/- 0.29 mm(3)/MC and 0.89 +/-
      0.04 mm(3)/MC (t = 48.43, p = 0.000). The ion levels of Cr and Co in the
      experimental group were also higher than those in the control group before 2.0
      MC. However there was no difference in the ion levels between 2.0 and 3.0 MC.
      CONCLUSIONS: This finding implies that the non-modular acetabular component of
      Durom total hip prosthesis is likely to become deformed during press-fit
      insertion, and that the deformation will result in increased volumetric wear and
      increased ion release. CLINICAL RELEVANCE: This study was determined to explore
      the deformation of the Durom cup after implantation and to clarify the impact of
      deformation on wear and ion release of the prosthesis. Deformation of the cup
      after implantation increases the wear of MOM bearings and the resulting ion
      levels. The clinical use of the Durom large head prosthesis should be with great
      care.

PMID- 23144695
TI  - Assessing predictors of changes in protein stability upon mutation using self
      consistency.
AB  - The ability to predict the effect of mutations on protein stability is important
      for a wide range of tasks, from protein engineering to assessing the impact of
      SNPs to understanding basic protein biophysics. A number of methods have been
      developed that make these predictions, but assessing the accuracy of these tools
      is difficult given the limitations and inconsistencies of the experimental data.
      We evaluate four different methods based on the ability of these methods to
      generate consistent results for forward and back mutations, and examine how this
      ability varies with the nature and location of the mutation. We find that, while
      one method seems to outperform the others, the ability of these methods to make
      accurate predictions is limited.

PMID- 23144696
TI  - Decreased reactive oxygen species production in cells with mitochondrial
      haplogroups associated with longevity.
AB  - Mitochondrial DNA (mtDNA) is highly polymorphic, and its variations in humans may
      contribute to individual differences in function. Zhang and colleagues found a
      strikingly higher frequency of a C150T transition in the D-loop of mtDNA from
      centenarians and twins of an Italian population, and also demonstrated that this
      base substitution causes a remodeling of the mtDNA 151 replication origin in
      human leukocytes and fibroblasts [1]. The C150T transition is a polymorphism
      associated with several haplogroups. To determine whether haplogroups that carry
      the C150T transition display any phenotype that may be advantageous for
      longevity, we analyzed cybrids carrying or not the C150T transition. These
      cybrids were obtained by fusing cytoplasts derived from human fibroblasts with
      human mtDNA-less cells (rho(0) cells). We chose for cybrid construction and
      analysis haplogroup-matched pairs of fibroblast strains containing or not the
      C150T transition. In particular, we used, as one pair of mtDNA donors, a
      fibroblast strain of the U3a haplogroup, carrying the C150T transition and a
      strain of the U-K2 haplogroup, without the C150T transition, and as another pair,
      fibroblasts of the J2b haplogroup, carrying the C150T transition and of the J1c
      haplogroup, without the C150T transition. We have found no association of
      respiratory capacity, mtDNA level, mitochondrial gene expression level, or growth
      rate with the presence of the C150T transition. However, we have found that the
      cybrids with haplogroups that include the C150T transition have in common a lower
      reactive oxygen species (ROS) production rate than the haplogroup-matched cybrids
      without that transition. Thus, the lower ROS production rate may be a factor in
      the increased longevity associated with the U and the J2 haplogroups. Of further
      interest, we found that cybrids with the U3a haplogroup exhibited a higher
      respiration rate than the other cybrids examined.

PMID- 23144697
TI  - Multiparametric analyses reveal the pH-dependence of silicon biomineralization in
      diatoms.
AB  - Diatoms, the major contributors of the global biogenic silica cycle in modern
      oceans, account for about 40% of global marine primary productivity. They are an
      important component of the biological pump in the ocean, and their assemblage can
      be used as useful climate proxies; it is therefore critical to better understand
      the changes induced by environmental pH on their physiology, silicification
      capability and morphology. Here, we show that external pH influences cell growth
      of the ubiquitous diatom Thalassiosira weissflogii, and modifies intracellular
      silicic acid and biogenic silica contents per cell. Measurements at the single
      cell level reveal that extracellular pH modifications lead to intracellular
      acidosis. To further understand how variations of the acid-base balance affect
      silicon metabolism and theca formation, we developed novel imaging techniques to
      measure the dynamics of valve formation. We demonstrate that the kinetics of
      valve morphogenesis, at least in the early stages, depends on pH. Analytical
      modeling results suggest that acidic conditions alter the dynamics of the
      expansion of the vesicles within which silica polymerization occurs, and probably
      its internal pH. Morphological analysis of valve patterns reveals that
      acidification also reduces the dimension of the nanometric pores present on the
      valves, and concurrently overall valve porosity. Variations in the valve silica
      network seem to be more correlated to the dynamics and the regulation of the
      morphogenesis process than the silicon incorporation rate. These multiparametric
      analyses from single-cell to cell-population levels demonstrate that several
      higher-level processes are sensitive to the acid-base balance in diatoms, and its
      regulation is a key factor for the control of pattern formation and silicon
      metabolism.

PMID- 23144698
TI  - Adipokines in psoriatic arthritis patients: the correlations with osteoclast
      precursors and bone erosions.
AB  - Significant bone remodeling with disordered osteoclastogenesis has been
      implicated in the pathogenesis of psoriatic arthritis (PsA). And there is a high
      prevalence of the metabolic syndrome (MS) in PsA patients. Adipokines, especially
      leptin and adiponectin, have recently been reported to be involved in the
      development and regulation of some autoimmune diseases. In this study, we
      examined the alternation of circulating osteoclastogenesis related cytokines
      [tumor necrosis factor-alpha (TNF-alpha), osteoprotegerin (OPG) and receptor
      activator of nuclear factor-kappaB ligand (RANKL)] and adipokines (leptin,
      adiponectin, resistin, chemerin, omentin) in PsA patients, and analysed the
      correlations between these factors and osteoclast precursors numbers,
      radiographic damage scores, and disease activity index. 41 PsA patients, 20
      psoriasis patients, and 24 healthy controls were recruited. Blood samples were
      obtained for detecting the levels of TNF-alpha, OPG, RANKL and the adipokines.
      The numbers of osteoclast precursors (OCs) in peripheral blood were assessed.
      Radiographs of affected joints in PsA patients were scored for erosion, joint
      space narrowing, osteolysis, and new bone formation. Compared with healthy
      controls, patients with PsA had higher TNF-alpha, RANKL, OCs, leptin and omentin
      but lower adiponectin and chemerin. Increased serum levels of TNF-alpha, RANKL,
      leptin, and omentin were positively correlated with OCs numbers. In contrast,
      serum adiponectin levels were decreased in PsA patients and negatively correlated
      with OCs numbers. TNF-alpha, RANKL and leptin were positively correlated with
      Psoriatic Arthritis Joint Activity Index (PsAJAI). Only TNF-alpha was positively
      correlated with radiographic damage scores. Our data demonstrated that systemic
      expression of soluble mediators of osteoclastogenesis and adipokines were
      disordered in PsA. Certain adipokines were elevated in the circulation of
      patients with PsA and might contribute to pathogenesis of arthritis. Prospective
      studies will be of interest to determine the pluripotent effects of adipokines on
      osteoclastogenesis in chronic inflammatory rheumatic diseases. Future studies may
      lead to novel therapeutic strategies.

PMID- 23144700
TI  - NLK is a novel therapeutic target for PTEN deficient tumour cells.
AB  - PTEN (Phosphatase and tensin homolog) is a tumour suppressor gene commonly
      defective in human cancer, and is thus a potentially important therapeutic
      target. Targeting tumour suppressor loss-of-function is possible by exploiting
      the genetic concept of synthetic lethality (SL). By combining the use of isogenic
      models of PTEN deficiency with high-throughput RNA interference (RNAi) screening,
      we have identified Nemo-Like Kinase (NLK) inhibition as being synthetically
      lethal with PTEN deficiency. This SL is likely mediated by the transcription
      factor FOXO1 (Forkhead box O1), an NLK substrate, as the selectivity of NLK gene
      silencing for PTEN deficient cells can be reversed by FOXO1 knockdown. In
      addition, we provide evidence that PTEN defective cells targeted by NLK gene
      depletion undergo senescence, suggesting that NLK function is critical for the
      continued proliferation of PTEN deficient cells. Taken together, these data
      provide new insight into the potential of targeting of NLK to treat a range of
      tumourigenic conditions characterised by PTEN deficiency.

PMID- 23144699
TI  - The success of acinetobacter species; genetic, metabolic and virulence
      attributes.
AB  - An understanding of why certain Acinetobacter species are more successful in
      causing nosocomial infections, transmission and epidemic spread in healthcare
      institutions compared with other species is lacking. We used genomic, phenotypic
      and virulence studies to identify differences between Acinetobacter species.
      Fourteen strains representing nine species were examined. Genomic analysis of six
      strains showed that the A. baumannii core genome contains many genes important
      for diverse metabolism and survival in the host. Most of the A. baumannii core
      genes were also present in one or more of the less clinically successful species.
      In contrast, when the accessory genome of an individual A. baumannii strain was
      compared to a strain of a less successful species (A. calcoaceticus RUH2202),
      many operons with putative virulence function were found to be present only in
      the A. baumannii strain, including the csu operon, the acinetobactin chromosomal
      cluster, and bacterial defence mechanisms. Phenotype microarray analysis showed
      that compared to A. calcoaceticus (RUH2202), A. baumannii ATCC 19606(T) was able
      to utilise nitrogen sources more effectively and was more tolerant to pH, osmotic
      and antimicrobial stress. Virulence differences were also observed, with A.
      baumannii ATCC 19606(T), A. pittii SH024, and A. nosocomialis RUH2624 persisting
      and forming larger biofilms on human skin than A. calcoaceticus. A. baumannii
      ATCC 19606(T) and A. pittii SH024 were also able to survive in a murine thigh
      infection model, whereas the other two species were eradicated. The current study
      provides important insights into the elucidation of differences in clinical
      relevance among Acinetobacter species.

PMID- 23144701
TI  - Short sleep duration is associated with shorter telomere length in healthy men:
      findings from the Whitehall II cohort study.
AB  - BACKGROUND: Shorter telomere length and poor sleep are more prevalent at older
      ages, but their relationship is uncertain. This study explored associations
      between sleep duration and telomere length in a sample of healthy middle and
      early old age people. METHODS: Participants were 434 men and women aged 63.3
      years on average drawn from the Whitehall II cohort study. Sleep duration was
      measured by self-report. RESULTS: There was a linear association between sleep
      duration and leukocyte telomere length in men but not in women (P = 0.035). Men
      reporting shorter sleep duration had shorter telomeres, independently of age,
      body mass index, smoking, educational attainment, current employment, cynical
      hostility scores and depressive symptoms. Telomeres were on average 6% shorter in
      men sleeping 5 hours or fewer compared with those sleeping more than 7 hours per
      night. CONCLUSION: This study adds to the growing literature relating sleep
      duration with biomarkers of aging, and suggests that shortening of telomeres
      might reflect mechanisms through which short sleep contributes to pathological
      conditions in older men.

PMID- 23144702
TI  - Candidate human genetic polymorphisms and severe malaria in a Tanzanian
      population.
AB  - Human genetic background strongly influences susceptibility to malaria infection
      and progression to severe disease and death. Classical genetic studies identified
      haemoglobinopathies and erythrocyte-associated polymorphisms, as protective
      against severe disease. High throughput genotyping by mass spectrometry allows
      multiple single nucleotide polymorphisms (SNPs) to be examined simultaneously. We
      compared the prevalence of 65 human SNP's, previously associated with altered
      risk of malaria, between Tanzanian children with and without severe malaria. Five
      hundred children, aged 1-10 years, with severe malaria were recruited from those
      admitted to hospital in Muheza, Tanzania and compared with matched controls.
      Genotyping was performed by Sequenom MassArray, and conventional PCR was used to
      detect deletions in the alpha-thalassaemia gene. SNPs in two X-linked genes were
      associated with altered risk of severe malaria in females but not in males:
      heterozygosity for one or other of two SNPs in the G6PD gene was associated with
      protection from all forms of severe disease whilst two SNPs in the gene encoding
      CD40L were associated with respiratory distress. A SNP in the adenyl cyclase 9
      (ADCY9) gene was associated with protection from acidosis whilst a polymorphism
      in the IL-1alpha gene (IL1A) was associated with an increased risk of acidosis.
      SNPs in the genes encoding IL-13 and reticulon-3 (RTN3) were associated with
      increased risk of cerebral malaria. This study confirms previously known genetic
      associations with protection from severe malaria (HbS, G6PD). It identifies two X
      linked genes associated with altered risk of severe malaria in females,
      identifies mutations in ADCY9, IL1A and CD40L as being associated with altered
      risk of severe respiratory distress and acidosis, both of which are characterised
      by high serum lactate levels, and also identifies novel genetic associations with
      severe malaria (TRIM5) and cerebral malaria(IL-13 and RTN3). Further studies are
      required to test the generality of these associations and to understand their
      functional consequences.

PMID- 23144703
TI  - Inhibition of pre-mRNA splicing by a synthetic Blom7alpha-interacting small RNA.
AB  - Originally the novel protein Blom7alpha was identified as novel pre-mRNA splicing
      factor that interacts with SNEV(Prp19/Pso4), an essential protein involved in
      extension of human endothelial cell life span, DNA damage repair, the ubiquitin
      proteasome system, and pre-mRNA splicing. Blom7alpha belongs to the heteronuclear
      ribonucleoprotein K homology (KH) protein family, displaying 2 KH domains, a well
      conserved and widespread RNA-binding motif. In order to identify specific
      sequence binding motifs, we here used Systematic Evolution of Ligands by
      Exponential Enrichment (SELEX) with a synthetic RNA library. Besides sequence
      motifs like (U/A)(1-4) C(2-6) (U/A)(1-5), we identified an AC-rich RNA-aptamer
      that we termed AK48 (Aptamer KH-binding 48), binding to Blom7alpha with high
      affinity. Addition of AK48 to pre-mRNA splicing reactions in vitro inhibited the
      formation of mature spliced mRNA and led to a slight accumulation of the H
      complex of the spliceosome. These results suggest that the RNA binding activity
      of Blom7alpha might be required for pre-mRNA splicing catalysis. The inhibition
      of in-vitro splicing by the small RNA AK48 indicates the potential use of small
      RNA molecules in targeting the spliceosome complex as a novel target for drug
      development.

PMID- 23144704
TI  - A characterization of the oral microbiome in allogeneic stem cell transplant
      patients.
AB  - BACKGROUND: The mouth is a complex biological structure inhabited by diverse
      bacterial communities. The purpose of this study is to describe the effects of
      allogeneic stem cell transplantation on the oral microbiota and to examine
      differences among those patients who acquired respiratory complications after
      transplantation. METHODOLOGY/PRINCIPAL FINDINGS: All patients were consented at
      the National Institutes of Health, Clinical Center. Bacterial DNA was analyzed
      from patients' oral specimens using the Human Oral Microbe Identification
      Microarray. The specimens were collected from four oral sites in 45 allogeneic
      transplantation patients. Specimens were collected at baseline prior to
      transplantation, after transplantation at the nadir of the neutrophil count and
      after myeloid engraftment. If respiratory signs and symptoms developed,
      additional specimens were obtained. Patients were followed for 100 days post
      transplantation. Eleven patients' specimens were subjected to further statistical
      analysis. Many common bacterial genera, such as Streptococcus, Veillonella,
      Gemella, Granulicatella and Camplyobacter were identified as being present before
      and after transplantation. Five of 11 patients developed respiratory
      complications following transplantation and there was preliminary evidence that
      the oral microbiome changed in their oral specimens. Cluster analysis and
      principal component analysis revealed this change in the oral microbiota.
      CONCLUSIONS/SIGNIFICANCE: After allogeneic transplantation, the oral bacterial
      community's response to a new immune system was not apparent and many of the most
      common core oral taxa remained unaffected. However, the oral microbiome was
      affected in patients who developed respiratory signs and symptoms after
      transplantation. The association related to the change in the oral microbiota and
      respiratory complications after transplantation will be validated by future
      studies using high throughput molecular methods.

PMID- 23144705
TI  - Neurocognition, insight and medication nonadherence in schizophrenia: a
      structural equation modeling approach.
AB  - OBJECTIVE: The aim of this study was to examine the complex relationships among
      neurocognition, insight and nonadherence in patients with schizophrenia. METHODS:
      DESIGN: Cross-sectional study. INCLUSION CRITERIA: Diagnosis of schizophrenia
      according to the DSM-IV-TR criteria. DATA COLLECTION: Neurocognition was assessed
      using a global approach that addressed memory, attention, and executive
      functions; insight was analyzed using the multidimensional 'Scale to assess
      Unawareness of Mental Disorder;' and nonadherence was measured using the
      multidimensional 'Medication Adherence Rating Scale.' ANALYSIS: Structural
      equation modeling (SEM) was applied to examine the non-straightforward
      relationships among the following latent variables: neurocognition, 'awareness of
      positive symptoms' and 'negative symptoms', 'awareness of mental disorder' and
      nonadherence. RESULTS: One hundred and sixty-nine patients were enrolled. The
      final testing model showed good fit, with normed chi(2) = 1.67, RMSEA = 0.063,
      CFI = 0.94, and SRMR = 0.092. The SEM revealed significant associations between
      (1) neurocognition and 'awareness of symptoms,' (2) 'awareness of symptoms' and
      'awareness of mental disorder' and (3) 'awareness of mental disorder' and
      nonadherence, mainly in the 'attitude toward taking medication' dimension. In
      contrast, there were no significant links between neurocognition and
      nonadherence, neurocognition and 'awareness of mental disorder,' and 'awareness
      of symptoms' and nonadherence. CONCLUSIONS: Our findings support the hypothesis
      that neurocognition influences 'awareness of symptoms,' which must be integrated
      into a higher level of insight (i.e., the 'awareness of mental disorder') to have
      an impact on nonadherence. These findings have important implications for the
      development of effective strategies to enhance medication adherence.

PMID- 23144707
TI  - Eating or meeting? Cluster analysis reveals intricacies of white shark
      (Carcharodon carcharias) migration and offshore behavior.
AB  - Elucidating how mobile ocean predators utilize the pelagic environment is vital
      to understanding the dynamics of oceanic species and ecosystems. Pop-up archival
      transmitting (PAT) tags have emerged as an important tool to describe animal
      migrations in oceanic environments where direct observation is not feasible.
      Available PAT tag data, however, are for the most part limited to geographic
      position, swimming depth and environmental temperature, making effective
      behavioral observation challenging. However, novel analysis approaches have the
      potential to extend the interpretive power of these limited observations. Here we
      developed an approach based on clustering analysis of PAT daily time-at-depth
      histogram records to distinguish behavioral modes in white sharks (Carcharodon
      carcharias). We found four dominant and distinctive behavioral clusters matching
      previously described behavioral patterns, including two distinctive offshore
      diving modes. Once validated, we mapped behavior mode occurrence in space and
      time. Our results demonstrate spatial, temporal and sex-based structure in the
      diving behavior of white sharks in the northeastern Pacific previously
      unrecognized including behavioral and migratory patterns resembling those of
      species with lek mating systems. We discuss our findings, in combination with
      available life history and environmental data, and propose specific testable
      hypotheses to distinguish between mating and foraging in northeastern Pacific
      white sharks that can provide a framework for future work. Our methodology can be
      applied to similar datasets from other species to further define behaviors during
      unobservable phases.

PMID- 23144706
TI  - Disulfide bond formation and ToxR activity in Vibrio cholerae.
AB  - Virulence factor production in Vibrio cholerae is complex, with ToxRS being an
      important part of the regulatory cascade. Additionally, ToxR is the
      transcriptional regulator for the genes encoding the major outer membrane porins
      OmpU and OmpT. ToxR is a transmembrane protein and contains two cysteine residues
      in the periplasmic domain. This study addresses the influence of the thiol
      disulfide oxidoreductase system DsbAB, ToxR cysteine residues and ToxR/ToxS
      interaction on ToxR activity. The results show that porin production correlates
      with ToxR intrachain disulfide bond formation, which depends on DsbAB. In
      contrast, formation of ToxR intrachain or interchain disulfide bonds is
      dispensable for virulence factor production and in vivo colonization. This study
      further reveals that in the absence of ToxS, ToxR interchain disulfide bond
      formation is facilitated, whereat cysteinyl dependent homo- and oligomerization
      of ToxR is suppressed if ToxS is coexpressed. In summary, new insights into gene
      regulation by ToxR are presented, demonstrating a mechanism by which ToxR
      activity is linked to a DsbAB dependent intrachain disulfide bond formation.

PMID- 23144708
TI  - Over-expression of DSCR1 protects against post-ischemic neuronal injury.
AB  - BACKGROUND AND PURPOSE: The Down syndrome candidate region 1 (DSCR1) gene is
      located on human chromosome 21 and its protein is over-expressed in brains of
      Down syndrome individuals. DSCR1 can modulate the activity of calcineurin, a
      phosphatase abundant in the brain, but its influence on stroke outcome is not
      clear. We compared stroke outcome in wildtype (WT) and transgenic (DSCR1-TG) mice
      which over-express isoform 1 of human DSCR1. METHODS: Transient cerebral ischemia
      was produced by occlusion of the middle cerebral artery for 0.5 h. After 23.5 h
      reperfusion, we assessed neurological impairment, brain infarct and edema volume,
      leukocyte infiltration and markers of inflammation. Intrinsic resistance to
      apoptosis following glucose deprivation was also assessed in primary cultures of
      WT and DSCR1-TG neurons. RESULTS: In contrast to WT, DSCR1-TG mice had an
      improved neurological deficit score, greater grip strength, attenuated infarct
      volume and brain swelling, and lacked hippocampal lesions after stroke.
      Expression of mouse DSCR1-1, but not DSCR1-4, mRNA and protein was increased by
      ischemia in both WT and DSCR1-TG. Brain calcineurin activity was increased to a
      similar degree after ischemia in each genotype. DSCR1-TG mice had fewer
      infiltrating neutrophils and activated microglia compared with WT, in association
      with an attenuated upregulation of several pro-inflammatory genes. Neurons from
      DSCR1-TG mice were more resistant than WT neurons to apoptotic cell death
      following 24 h of glucose deprivation. CONCLUSIONS: Over-expression of DSCR1 in
      mice improves outcome following stroke. Mechanisms underlying this protection may
      involve calcineurin-independent, anti-inflammatory and anti-apoptotic effects
      mediated by DSCR1 in neurons.

PMID- 23144709
TI  - iNuc-PhysChem: a sequence-based predictor for identifying nucleosomes via
      physicochemical properties.
AB  - Nucleosome positioning has important roles in key cellular processes. Although
      intensive efforts have been made in this area, the rules defining nucleosome
      positioning is still elusive and debated. In this study, we carried out a
      systematic comparison among the profiles of twelve DNA physicochemical features
      between the nucleosomal and linker sequences in the Saccharomyces cerevisiae
      genome. We found that nucleosomal sequences have some position-specific
      physicochemical features, which can be used for in-depth studying nucleosomes.
      Meanwhile, a new predictor, called iNuc-PhysChem, was developed for
      identification of nucleosomal sequences by incorporating these physicochemical
      properties into a 1788-D (dimensional) feature vector, which was further reduced
      to a 884-D vector via the IFS (incremental feature selection) procedure to
      optimize the feature set. It was observed by a cross-validation test on a
      benchmark dataset that the overall success rate achieved by iNuc-PhysChem was
      over 96% in identifying nucleosomal or linker sequences. As a web-server, iNuc
      PhysChem is freely accessible to the public at
      http://lin.uestc.edu.cn/server/iNuc-PhysChem. For the convenience of the vast
      majority of experimental scientists, a step-by-step guide is provided on how to
      use the web-server to get the desired results without the need to follow the
      complicated mathematics that were presented just for the integrity in developing
      the predictor. Meanwhile, for those who prefer to run predictions in their own
      computers, the predictor's code can be easily downloaded from the web-server. It
      is anticipated that iNuc-PhysChem may become a useful high throughput tool for
      both basic research and drug design.

PMID- 23144712
TI  - Prey detection and prey capture in copepod nauplii.
AB  - Copepod nauplii are either ambush feeders that feed on motile prey or they
      produce a feeding current that entrains prey cells. It is unclear how ambush and
      feeding-current feeding nauplii perceive and capture prey. Attack jumps in ambush
      feeding nauplii should not be feasible at low Reynolds numbers due to the thick
      viscous boundary layer surrounding the attacking nauplius. We use high-speed
      video to describe the detection and capture of phytoplankton prey by the nauplii
      of two ambush feeding species (Acartia tonsa and Oithona davisae) and by the
      nauplii of one feeding-current feeding species (Temora longicornis). We
      demonstrate that the ambush feeders both detect motile prey remotely. Prey
      detection elicits an attack jump, but the jump is not directly towards the prey,
      such as has been described for adult copepods. Rather, the nauplius jumps past
      the prey and sets up an intermittent feeding current that pulls in the prey from
      behind towards the mouth. The feeding-current feeding nauplius detects prey
      arriving in the feeding current but only when the prey is intercepted by the
      setae on the feeding appendages. This elicits an altered motion pattern of the
      feeding appendages that draws in the prey.

PMID- 23144710
TI  - Quantitative proteomic analysis of Niemann-Pick disease, type C1 cerebellum
      identifies protein biomarkers and provides pathological insight.
AB  - Niemann-Pick disease, type C1 (NPC1) is a fatal, neurodegenerative disorder for
      which there is no definitive therapy. In NPC1, a pathological cascade including
      neuroinflammation, oxidative stress and neuronal apoptosis likely contribute to
      the clinical phenotype. While the genetic cause of NPC1 is known, we sought to
      gain a further understanding into the pathophysiology by identifying
      differentially expressed proteins in Npc1 mutant mouse cerebella. Using two
      dimensional gel electrophoresis and mass spectrometry, 77 differentially
      expressed proteins were identified in Npc1 mutant mice cerebella compared to
      controls. These include proteins involved in glucose metabolism,
      detoxification/oxidative stress and Alzheimer disease-related proteins.
      Furthermore, members of the fatty acid binding protein family, including FABP3,
      FABP5 and FABP7, were found to have altered expression in the Npc1 mutant
      cerebellum relative to control. Translating our findings from the murine model to
      patients, we confirm altered expression of glutathione s-transferase alpha,
      superoxide dismutase, and FABP3 in cerebrospinal fluid of NPC1 patients relative
      to pediatric controls. A subset of NPC1 patients on miglustat, a
      glycosphingolipid synthesis inhibitor, showed significantly decreased levels of
      FABP3 compared to patients not on miglustat therapy. This study provides an
      initial report of dysregulated proteins in NPC1 which will assist with further
      investigation of NPC1 pathology and facilitate implementation of therapeutic
      trials.

PMID- 23144711
TI  - Usp14 deficiency increases tau phosphorylation without altering tau degradation
      or causing tau-dependent deficits.
AB  - Regulated protein degradation by the proteasome plays an essential role in the
      enhancement and suppression of signaling pathways in the nervous system.
      Proteasome-associated factors are pivotal in ensuring appropriate protein
      degradation, and we have previously demonstrated that alterations in one of these
      factors, the proteasomal deubiquitinating enzyme ubiquitin-specific protease 14
      (Usp14), can lead to proteasome dysfunction and neurological disease. Recent
      studies in cell culture have shown that Usp14 can also stabilize the expression
      of over-expressed, disease-associated proteins such as tau and ataxin-3. Using
      Usp14-deficient ax(J) mice, we investigated if loss of Usp14 results in decreased
      levels of endogenous tau and ataxin-3 in the nervous system of mice. Although
      loss of Usp14 did not alter the overall neuronal levels of tau and ataxin-3, we
      found increased levels of phosphorylated tau that correlated with the onset of
      axonal varicosities in the Usp14-deficient mice. These changes in tau
      phosphorylation were accompanied by increased levels of activated phospho-Akt,
      phosphorylated MAPKs, and inactivated phospho-GSK3beta. However, genetic ablation
      of tau did not alter any of the neurological deficits in the Usp14-deficient
      mice, demonstrating that increased levels of phosphorylated tau do not
      necessarily lead to neurological disease. Due to the widespread activation of
      intracellular signaling pathways induced by the loss of Usp14, a better
      understanding of the cellular pathways regulated by the proteasome is required
      before effective proteasomal-based therapies can be used to treat chronic
      neurological diseases.

PMID- 23144713
TI  - Impact of AT2 receptor deficiency on postnatal cardiovascular development.
AB  - BACKGROUND: The angiotensin II receptor subtype 2 (AT2 receptor) is ubiquitously
      and highly expressed in early postnatal life. However, its role in postnatal
      cardiac development remained unclear. METHODOLOGY/PRINCIPAL FINDINGS: Hearts from
      1, 7, 14 and 56 days old wild-type (WT) and AT2 receptor-deficient (KO) mice were
      extracted for histomorphometrical analysis as well as analysis of cardiac
      signaling and gene expression. Furthermore, heart and body weights of examined
      animals were recorded and echocardiographic analysis of cardiac function as well
      as telemetric blood pressure measurements were performed. Moreover, gene
      expression, sarcomere shortening and calcium transients were examined in
      ventricular cardiomyocytes isolated from both genotypes. KO mice exhibited an
      accelerated body weight gain and a reduced heart to body weight ratio as compared
      to WT mice in the postnatal period. However, in adult KO mice the heart to body
      weight ratio was significantly increased most likely due to elevated systemic
      blood pressure. At postnatal day 7 ventricular capillarization index and the
      density of alpha-smooth muscle cell actin-positive blood vessels were higher in
      KO mice as compared to WT mice but normalized during adolescence.
      Echocardiographic assessment of cardiac systolic function at postnatal day 7
      revealed decreased contractility of KO hearts in response to beta-adrenergic
      stimulation. Moreover, cardiomyocytes from KO mice showed a decreased sarcomere
      shortening and an increased peak Ca(2+) transient in response to isoprenaline
      when stimulated concomitantly with angiotensin II. CONCLUSION: The AT2 receptor
      affects postnatal cardiac growth possibly via reducing body weight gain and
      systemic blood pressure. Moreover, it moderately attenuates postnatal
      vascularization of the heart and modulates the beta adrenergic response of the
      neonatal heart. These AT2 receptor-mediated effects may be implicated in the
      physiological maturation process of the heart.

PMID- 23144715
TI  - Development of a quantitative methylation-specific polymerase chain reaction
      method for monitoring beta cell death in type 1 diabetes.
AB  - DNA methylation is a mechanism by which cells control gene expression, and cell
      specific genes often exhibit unique patterns of DNA methylation. We previously
      reported that the mouse insulin-2 gene (Ins2) promoter has three potential
      methylation (CpG) sites, all of which are unmethylated in insulin-producing cells
      but methylated in other tissues. In this study we examined Ins2 exon 2 and found
      a similar tissue-specific methylation pattern. These methylation patterns can
      differentiate between DNA from insulin-producing beta cells and other tissues. We
      hypothesized that damaged beta cells release their DNA into circulation at the
      onset of type 1 diabetes mellitus (T1DM) and sought to develop a quantitative
      methylation-specific polymerase chain reaction (qMSP) assay for circulating beta
      cell DNA to monitor the loss of beta cells. Methylation-specific primers were
      designed to interrogate two or more CpG in the same assay. The cloned mouse Ins2
      gene was methylated in vitro and used for development of the qMSP assay. We found
      the qMSP method to be sensitive and specific to differentiate between insulin
      producing cells and other tissues with a detection limit of 10 copies in the
      presence of non-specific genomic DNA background. We also compared different
      methods for data analysis and found that the Relative Expression Ratio method is
      the most robust method since it incorporates both a reference value to normalize
      day-to-day variability as well as PCR reaction efficiencies to normalize between
      the methylation-specific and bisulfite-specific components of the calculations.
      The assay was applied in the streptozotocin-treated diabetic mouse model and
      detected a significant increase in circulating beta cell DNA before the rise in
      blood glucose level. These results demonstrate that this qMSP assay can be used
      for monitoring circulating DNA from insulin-producing cells, which will provide
      the basis for development of assays to detect beta cell destruction in early
      T1DM.

PMID- 23144714
TI  - UPR-induced resistance to etoposide is downstream of PERK and independent of
      changes in topoisomerase IIalpha levels.
AB  - BACKGROUND: The unfolded protein response (UPR) is regulated by three ER
      localized, transmembrane signal transducers that control distinct aspects of the
      UPR. We previously reported that both increased resistance to etoposide and a
      reduction in Topoisomerase IIalpha protein levels were a direct response of UPR
      activation, and the latter occurred independent of changes in Topo IIalpha mRNA
      levels. We have now examined the contribution of each of the three up-stream
      transducers of the UPR, as well as some of their downstream targets in affecting
      decreased expression of Topo IIalpha protein and increased drug resistance.
      PRINCIPAL FINDINGS: Our data revealed that while Ire1 activation led to Topo
      IIalpha loss at the protein level it did not contribute to changes in sensitivity
      to etoposide. The decreased expression of Topo IIalpha protein was not downstream
      of XBP-1, in keeping with the fact that Topo IIalpha transcription was not
      affected by ER stress. Conversely, PERK activation did not contribute to changes
      in Topo IIalpha protein levels, but it did play a significant role in the UPR
      induced decreased sensitivity to etoposide. Several cellular responses downstream
      of PERK were examined for their potential to contribute to resistance. The ATF6
      arm of the UPR did not significantly contribute to etoposide resistance within
      the time frame of our experiments. CONCLUSIONS AND SIGNIFICANCE: In toto, our
      data demonstrate that UPR-induced changes in Topo IIalpha protein levels are not
      responsible for resistance to etoposide as has been previously hypothesized, and
      instead demonstrate that the PERK branch plays a Topo IIalpha-independent role in
      altered sensitivity to this drug.

PMID- 23144716
TI  - Evidence for abasic site sugar phosphate-mediated cytotoxicity in alkylating
      agent treated Saccharomyces cerevisiae.
AB  - To better understand alkylating agent-induced cytotoxicity and the base lesion
      DNA repair process in Saccharomyces cerevisiae, we replaced the RAD27(FEN1) open
      reading frame (ORF) with the ORF of the bifunctional human repair enzyme DNA
      polymerase (Pol) beta. The aim was to probe the effect of removal of the incised
      abasic site 5'-sugar phosphate group (i.e., 5'-deoxyribose phosphate or 5'-dRP)
      in protection against methyl methanesulfonate (MMS)-induced cytotoxicity. In S.
      cerevisiae, Rad27(Fen1) was suggested to protect against MMS-induced cytotoxicity
      by excising multinucleotide flaps generated during repair. However, we proposed
      that the repair intermediate with a blocked 5'-end, i.e., 5'-dRP group, is the
      actual cytotoxic lesion. In providing a 5'-dRP group removal function mediated by
      dRP lyase activity of Pol beta, the effects of the 5'-dRP group were separated
      from those of the multinucleotide flap itself. Human Pol beta was expressed in S.
      cerevisiae, and this partially rescued the MMS hypersensitivity observed with
      rad27(fen1)-null cells. To explore this rescue effect, altered forms of Pol beta
      with site-directed eliminations of either the 5'-dRP lyase or polymerase activity
      were expressed in rad27(fen1)-null cells. The 5'-dRP lyase, but not the
      polymerase activity, conferred the resistance to MMS. These results suggest that
      after MMS exposure, the 5'-dRP group in the repair intermediate is cytotoxic and
      that Rad27(Fen1) protection against MMS in wild-type cells is due to elimination
      of the 5'-dRP group.

PMID- 23144717
TI  - BeeDoctor, a versatile MLPA-based diagnostic tool for screening bee viruses.
AB  - The long-term decline of managed honeybee hives in the world has drawn
      significant attention to the scientific community and bee-keeping industry. A
      high pathogen load is believed to play a crucial role in this phenomenon, with
      the bee viruses being key players. Most of the currently characterized honeybee
      viruses (around twenty) are positive stranded RNA viruses. Techniques based on
      RNA signatures are widely used to determine the viral load in honeybee colonies.
      High throughput screening for viral loads necessitates the development of a
      multiplex polymerase chain reaction approach in which different viruses can be
      targeted simultaneously. A new multiparameter assay, called "BeeDoctor", was
      developed based on multiplex-ligation probe dependent amplification (MLPA)
      technology. This assay detects 10 honeybee viruses in one reaction. "BeeDoctor"
      is also able to screen selectively for either the positive strand of the targeted
      RNA bee viruses or the negative strand, which is indicative for active viral
      replication. Due to its sensitivity and specificity, the MLPA assay is a useful
      tool for rapid diagnosis, pathogen characterization, and epidemiology of viruses
      in honeybee populations. "BeeDoctor" was used for screening 363 samples from
      apiaries located throughout Flanders; the northern half of Belgium. Using the
      "BeeDoctor", virus infections were detected in almost eighty percent of the
      colonies, with deformed wing virus by far the most frequently detected virus and
      multiple virus infections were found in 26 percent of the colonies.

PMID- 23144718
TI  - Metagenomic profiling of microbial composition and antibiotic resistance
      determinants in Puget Sound.
AB  - Human-health relevant impacts on marine ecosystems are increasing on both spatial
      and temporal scales. Traditional indicators for environmental health monitoring
      and microbial risk assessment have relied primarily on single species analyses
      and have provided only limited spatial and temporal information. More high
      throughput, broad-scale approaches to evaluate these impacts are therefore needed
      to provide a platform for informing public health. This study uses shotgun
      metagenomics to survey the taxonomic composition and antibiotic resistance
      determinant content of surface water bacterial communities in the Puget Sound
      estuary. Metagenomic DNA was collected at six sites in Puget Sound in addition to
      one wastewater treatment plant (WWTP) that discharges into the Sound and
      pyrosequenced. A total of ~550 Mbp (1.4 million reads) were obtained, 22 Mbp of
      which could be assembled into contigs. While the taxonomic and resistance
      determinant profiles across the open Sound samples were similar, unique
      signatures were identified when comparing these profiles across the open Sound, a
      nearshore marina and WWTP effluent. The open Sound was dominated by alpha
      Proteobacteria (in particular Rhodobacterales sp.), gamma-Proteobacteria and
      Bacteroidetes while the marina and effluent had increased abundances of
      Actinobacteria, beta-Proteobacteria and Firmicutes. There was a significant
      increase in the antibiotic resistance gene signal from the open Sound to marina
      to WWTP effluent, suggestive of a potential link to human impacts. Mobile genetic
      elements associated with environmental and pathogenic bacteria were also
      differentially abundant across the samples. This study is the first comparative
      metagenomic survey of Puget Sound and provides baseline data for further
      assessments of community composition and antibiotic resistance determinants in
      the environment using next generation sequencing technologies. In addition, these
      genomic signals of potential human impact can be used to guide initial public
      health monitoring as well as more targeted and functionally-based investigations.

PMID- 23144719
TI  - Parental acceptance of HPV vaccine in Peru: a decision framework.
AB  - OBJECTIVE AND METHOD: Cervical cancer is the third most common cancer affecting
      women worldwide and it is an important cause of death, especially in developing
      countries. Cervical cancer is caused by human papillomavirus (HPV) and can be
      prevented by HPV vaccine. The challenge is to expand vaccine availability to
      countries where it is most needed. In 2008 Peru's Ministry of Health implemented
      a demonstration project involving 5(th) grade girls in primary schools in the
      Piura region. We designed and conducted a qualitative study of the decision
      making process among parents of girls, and developed a conceptual model
      describing the process of HPV vaccine acceptance. RESULTS: We found a nonlinear
      HPV decision-making process that evolved over time. Initially, the vaccine's
      newness, the requirement of written consent, and provision of information were
      important. If information was sufficient and provided by credible sources, many
      parents accepted the vaccine. Later, after obtaining additional information from
      teachers, health personnel, and other trusted sources, more parents accepted
      vaccination. An understanding of the issues surrounding the vaccine developed,
      parents overcome fears and rumors, and engaged in family negotiations-including
      hearing the girl's voice in the decision-making process. The concept of
      prevention (cancer as danger, future health, and trust in vaccines) combined with
      pragmatic factors (no cost, available at school) and the credibility of the offer
      (information in the media, recommendation of respected authority figure) were
      central to motivations that led parents to decide to vaccinate their daughters. A
      lack of confidence in the health system was the primary inhibitor of vaccine
      acceptance. CONCLUSIONS: Health personnel and teachers are credible sources of
      information and can provide important support to HPV vaccination campaigns.

PMID- 23144720
TI  - Identification of She3 as an SCF(Grr1) substrate in budding yeast.
AB  - The highly orchestrated progression of the cell cycle depends on the degradation
      of many regulatory proteins at different cell cycle stages. One of the key cell
      cycle ubiquitin ligases is the Skp1-cullin-F-box (SCF) complex. Acting in concert
      with the substrate-binding F-box protein Grr1, SCF(Grr1) promotes the degradation
      of cell cycle regulators as well as various metabolic enzymes. Using a yeast two
      hybrid assay with a Grr1 derivative as the bait, we identified She3, which is an
      adaptor protein in the asymmetric mRNA transport system, as a novel Grr1
      substrate. We generated stabilized She3 mutants, which no longer bound to Grr1,
      and found that the degradation of She3 is not required for regulating asymmetric
      mRNA transport. However, She3 stabilization leads to slower growth compared to
      wild-type cells in a co-culture assay, demonstrating that the degradation of She3
      by Grr1 is required for optimal cell growth.

PMID- 23144721
TI  - Transforming microbial genotyping: a robotic pipeline for genotyping bacterial
      strains.
AB  - Microbial genotyping increasingly deals with large numbers of samples, and data
      are commonly evaluated by unstructured approaches, such as spread-sheets. The
      efficiency, reliability and throughput of genotyping would benefit from the
      automation of manual manipulations within the context of sophisticated data
      storage. We developed a medium- throughput genotyping pipeline for MultiLocus
      Sequence Typing (MLST) of bacterial pathogens. This pipeline was implemented
      through a combination of four automated liquid handling systems, a Laboratory
      Information Management System (LIMS) consisting of a variety of dedicated
      commercial operating systems and programs, including a Sample Management System,
      plus numerous Python scripts. All tubes and microwell racks were bar-coded and
      their locations and status were recorded in the LIMS. We also created a
      hierarchical set of items that could be used to represent bacterial species,
      their products and experiments. The LIMS allowed reliable, semi-automated,
      traceable bacterial genotyping from initial single colony isolation and sub
      cultivation through DNA extraction and normalization to PCRs, sequencing and MLST
      sequence trace evaluation. We also describe robotic sequencing to facilitate
      cherrypicking of sequence dropouts. This pipeline is user-friendly, with a
      throughput of 96 strains within 10 working days at a total cost of < ?25 per
      strain. Since developing this pipeline, >200,000 items were processed by two to
      three people. Our sophisticated automated pipeline can be implemented by a small
      microbiology group without extensive external support, and provides a general
      framework for semi-automated bacterial genotyping of large numbers of samples at
      low cost.

PMID- 23144722
TI  - In vitro immunomodulation of a whole blood IFN-gamma release assay enhances T
      cell responses in subjects with latent tuberculosis infection.
AB  - BACKGROUND: Activation of innate immunity via pathogen recognition receptors
      (PRR) modulates adaptive immune responses. PRR ligands are being exploited as
      vaccine adjuvants and as therapeutics, but their utility in diagnostics has not
      been explored. Interferon-gamma (IFN-gamma) release assays (IGRAs) are functional
      T cell assays used to diagnose latent tuberculosis infection (LTBI); however,
      novel approaches are needed to improve their sensitivity. METHODS: In vitro
      immunomodulation of a whole blood IGRA (QuantiFERON(r)-TB GOLD In-Tube) with Toll
      like receptor agonists poly(I:C), LPS, and imiquimod was performed on blood from
      subjects with LTBI and negative controls. RESULTS: In vitro immunomodulation
      significantly enhanced the response of T cells stimulated with M. tuberculosis
      antigens from subjects with LTBI but not from uninfected controls.
      Immunomodulation of IGRA revealed T cell responses in subjects with LTBI whose T
      cells otherwise do not respond to in vitro stimulation with antigens alone.
      Similar to their in vivo functions, addition of poly(I:C) and LPS to whole blood
      induced secretion of inflammatory cytokines and IFN-alpha and enhanced the
      surface expression of antigen presenting and costimulatory molecules on antigen
      presenting cells. CONCLUSIONS: In vitro immunomodulation of whole blood IGRA may
      be an effective strategy for enhancing the sensitivity of T cells for diagnosis
      of LTBI.

PMID- 23144723
TI  - Cardiac gene activation analysis in mammalian non-myoblasic cells by Nkx2-5,
      Tbx5, Gata4 and Myocd.
AB  - Cardiac transcription factors are master regulators during heart development.
      Some were shown to transdifferentiate tail tip and cardiac fibroblasts into
      cardiomyocytes. However, recent studies have showed that controversies exist.
      Potential difference in tail tip and cardiac fibroblast isolation may possibly
      confound the observations. Moreover, due to the use of a cardiac reporter (Myh6)
      selection strategy for induced cardiomyocyte enrichment, and the lack of tracking
      signals for each transcription factors, individual roles of each transcription
      factors in activating cardiac gene expression in mammalian non-myoblastic cells
      have never been elucidated. Answers to these questions are an important step
      toward cardiomyocyte regeneration. Because mouse 10T1/2 fibroblasts are non
      myoblastic in nature and can be induced to express genes of all three types of
      muscle cells, they are an ideal model for the analysis of cardiac and non-cardiac
      gene activation after induction. We constructed bi-cistronic lentiviral vectors,
      capable of expressing cardiac transcription factors along with different
      fluorescent tracking signals. By infecting 10T1/2 fibroblasts with Nkx2-5, Tbx5,
      Gata4 or Myocd cardiac transcription factor lentivirus alone or different
      combinations, we found that only Tbx5+Myocd and Tbx5+Gata4+Myocd combinations
      induced Myh6 and Tnnt2 cardiac marker protein expression. Microarray-based gene
      ontology analysis revealed that Tbx5 alone activated genes involved in the Wnt
      receptor signaling pathway and inhibited genes involved in a number of cardiac
      related processes. Myocd alone activated genes involved in a number of cardiac
      related processes and inhibited genes involved in the Wnt receptor signaling
      pathway and non-cardiac processes. Gata4 alone inhibited genes involved in non
      cardiac processes. Tbx5+Gata4+Myocd was the most effective activator of genes
      associated with cardiac-related processes. Unlike Tbx5, Gata4, Myocd alone or
      Tbx5+Myocd, Tbx5+Gata4+Myocd activated the fewest genes associated with non
      cardiac processes. Conclusively, Tbx5, Gata4 and Myocd play different roles in
      cardiac gene activation in mammalian non-myoblastic cells. Tbx5+Gata4+Myocd
      activates the most cardiac and the least non-cardiac gene expression.

PMID- 23144724
TI  - Englerin a selectively induces necrosis in human renal cancer cells.
AB  - The number of renal cancers has increased over the last ten years and patient
      survival in advanced stages remains very poor. Therefore, new therapeutic
      approaches for renal cancer are essential. Englerin A is a natural product with a
      very potent and selective cytotoxicity against renal cancer cells. This makes it
      a promising drug candidate that may improve current treatment standards for
      patients with renal cancers in all stages. However, little is known about
      englerin A's mode of action in targeting specifically renal cancer cells. Our
      study is the first to investigate the biological mechanism of englerin A action
      in detail. We report that englerin A is specific for renal tumor cells and does
      not affect normal kidney cells. We find that englerin A treatment induces
      necrotic cell death in renal cancer cells but not in normal kidney cells. We
      further show that autophagic and pyroptotic proteins are unaffected by the
      compound and that necrotic signaling in these cells coincided with production of
      reactive oxygen species and calcium influx into the cytoplasm. As the first study
      to analyze the biological effects of englerin A, our work provides an important
      basis for the evaluation and validation of the compound's use as an anti-tumor
      drug. It also provides a context in which to identify the specific target or
      targets of englerin A in renal cancer cells.

PMID- 23144725
TI  - Prevalence of acute kidney injury and prognostic significance in patients with
      acute myocarditis.
AB  - OBJECTIVE: Myocarditis is an inflammation of the myocardium. The condition is
      commonly associated with rapid disease progression and often results in profound
      shock. Impaired renal function is the result of impairment in end-organ perfusion
      and is highly prevalent among critically ill patients. The aim of this study was
      to evaluate the incidence of acute kidney injury (AKI) and identify the
      relationship between AKI and the prognosis of patients with acute myocarditis.
      DESIGN, MEASUREMENTS AND MAIN RESULTS: This retrospective study reviewed the
      medical records of 101 patients suffering from acute myocarditis between 1996 and
      2011. Sixty of these patients (59%) developed AKI within 48 hours of being
      hospitalized. AKI defined as AKIN stage 3 (p = 0.007) and SOFA score (p = 0.03)
      were identified as predictors of in-hospital mortality in multivariate analysis.
      The conditional effect plot of the estimated risk against SOFA score upon
      admission categorized according to the AKIN stages showed that the risk of in
      hospital mortality was highest among patients in AKIN stage 3 with a high SOFA
      score. CONCLUSIONS: Among patients with acute myocarditis, AKI defined as AKIN
      stage 3 and elevated SOFA score were associated with unfavorable outcomes. AKIN
      classification is a simple, reproducible, and easily applied evaluation tool
      capable of providing objective information related to the clinical prognosis of
      patients with acute myocarditis.

PMID- 23144727
TI  - Assessing European egg parasitoids as a mean of controlling the invasive South
      American tomato pinworm Tuta absoluta.
AB  - The South American tomato pinworm (Tuta absoluta) has recently invaded Europe and
      is rapidly spreading in the Afro-Eurasian continent where it is becoming a major
      pest on tomato crops. Laboratory tests were undertaken to evaluate the potential
      of 29 European strains of Trichogramma parasitoids to control T. absoluta. In
      addition to the host itself, the host plant (tomato) was used during the
      laboratory tests in order to increase the chance of selecting the best parasitoid
      strains. Trichogramma females were placed with T. absoluta eggs on a tomato
      leaflet in tubes. We compared the parasitism of T. absoluta by the various
      Trichogramma species tested to the Trichogramma species currently commercially
      available for the pest control in Europe, i.e. Trichogramma achaeae. Thereafter,
      the more promising strains were tested on a larger scale, in mesocosm (i.e. cages
      in greenhouses) and in greenhouse compartments to evaluate efficiency of
      laboratory selected strains under cropping conditions. The most efficient strain
      from the laboratory screening trials did not perform as efficiently under the
      greenhouse conditions. We discuss differences in parasitism levels among species
      and strains and among the different scales tested in the experiments, as well as
      implications of these results for further screening for biocontrol agents.

PMID- 23144726
TI  - Promise(s) of mesenchymal stem cells as an in vitro model system to depict pre
      diabetic/diabetic milieu in WNIN/GR-Ob mutant rats.
AB  - BACKGROUND: Development of model systems have helped to a large extent, in
      bridging gap to understand the mechanism(s) of disease including diabetes.
      Interestingly, WNIN/GR-Ob rats (Mutants), established at National Centre for
      Laboratory Animals (NCLAS) of National Institute of Nutrition (NIN), form a
      suitable model system to study obesity with Type 2 diabetes (T2D) demonstrating
      several secondary complications (cataract, cardiovascular complications,
      infertility, nephropathy etc). The present study has been carried out to explore
      the potent application(s) of multipotent stem cells such as bone marrow
      mesenchymal stem cells (BM-MSCs), to portray features of pre-diabetic/T2D vis-a
      vis featuring obesity, with impaired glucose tolerance (IGT), hyperinsulinemia
      (HI) and insulin resistance (IR) seen with Mutant rats akin to human situation.
      METHODOLOGY/PRINCIPAL FINDINGS: Primary cultures of BM-MSCs (third passage) from
      Mutants, its lean littermate (Lean) and parental control (Control) were
      characterized for: proliferation markers, disease memory to mark
      obesity/T2D/HI/IR which included phased gene expression studies for
      adipogenic/pancreatic lineages, inflammatory markers and differentiation ability
      to form mature adipocytes/Insulin-like cellular aggregates (ILCAs). The data
      showed that BM-MSCs from Mutant demonstrated a state of disease memory, depicted
      by an upregulated expression of inflammatory markers (IL-6, TNFalpha); increased
      stem cell recruitment (Oct-4, Sox-2) and proliferation rates (CD90+/CD29+, PDA,
      'S' phase of cell cycle by FACS and BrdU incorporation); accelerated preadipocyte
      induction (Dact-1, PPARgamma2) with a quantitative increase in mature adipocyte
      formation (Leptin); ILCAs, which were non-responsive to high glucose did confer
      the Obese/T2D memory in Mutants. Further, these observations were in compliance
      with the anthropometric data. CONCLUSIONS: Given the ease of accessibility and
      availability of MSCs, the present study form the basis to report for the first
      time, application of BM-MSCs as a feasible in vitro model system to portray the
      disease memory of pre-clinical/T2D with IR - a major metabolic disorder of global
      concern.

PMID- 23144728
TI  - Enantioselective induction of a glutathione-S-transferase, a glutathione
      transporter and an ABC transporter in maize by Metolachlor and its (S)-isomer.
AB  - The metabolism of chiral herbicides in plants remains poorly understood.
      Glutathione conjugation reactions are one of the principal mechanisms that plants
      utilize to detoxify xenobiotics. The induction by rac- and S-metolachlor of the
      expression of three genes, ZmGST27, ZmGT1 and ZmMRP1, encoding respectively a
      glutathione-S-transferase, a glutathione transporter and an ATP-binding cassette
      (ABC) transporter was studied in maize. The results demonstrate that the inducing
      effect of rac- and S-metolachlor on the expression of ZmGST27 and ZmGT1 is
      comparable. However, the inducing effect of rac-metolachlor on ZmMRP1 expression
      is more pronounced than that of S-metolachlor. Furthermore, vanadate, an ABC
      transporter inhibitor, could greatly reduce the difference in herbicidal activity
      between rac- and S-metolachlor. These results suggest that the ABC transporters
      may preferentially transport conjugates of rac-metolachlor, leading to a faster
      metabolism of the latter. Through comparing the expression of ZmGST27, ZmMRP1 and
      ZmGT1 after treatment by rac- and S-metolachlor, we provide novel insights into
      the metabolic processes of chiral herbicides in plants.

PMID- 23144730
TI  - Performance evaluation of the Maxwell 16 System for extraction of influenza virus
      RNA from diverse samples.
AB  - This study evaluated the performance of the Maxwell 16 System (Promega) for
      extraction of influenza virus (flu-v) RNA from diverse samples compared to a
      classical manual method (QIAamp Kit, QIAGEN). Following extraction by the two
      methods, all samples were analyzed by Real-time RT-PCR. Results revealed that the
      use of the standard Maxwell 16 protocol (Maxwell 16-S) resulted in good linearity
      and precision across a wide concentration range and higher sensitivity of
      detection from flu-v stock suspensions than the manual method. Compared with the
      latter method, Maxwell 16-S extracted RNA more efficiently (higher RNA yield
      and/or fewer PCR inhibitors) from throat swabs and bronchoalveolar lavage fluids,
      while both methods performed comparably on fecal samples from human and poultry
      in terms of overall threshold cycle values and detection rates although the
      Maxwell 16-S co-purified more inhibitors from fecal samples. The capacity of this
      system to remove inhibitors from fecal matrix was improved by using a modified
      Maxwell 16 protocol with a reduced sample input, which eliminated all false
      negatives produced by the Maxwell 16-S. These findings suggest that the Maxwell
      16 System is suitable for RNA extraction from multiple-source samples for
      diagnosis of influenza and viral load determination and that a proper reduction
      in starting sample volume may improve the detection of flu-v from complex
      matrices such as feces. Additionally, this system allows flexible sample
      throughput and labor-saving sample processing with little or no risk of cross
      contamination.

PMID- 23144729
TI  - Novel genes and pathways modulated by syndecan-1: implications for the
      proliferation and cell-cycle regulation of malignant mesothelioma cells.
AB  - Malignant pleural mesothelioma is a highly malignant tumor, originating from
      mesothelial cells of the serous cavities. In mesothelioma the expression of
      syndecan-1 correlates to epithelioid morphology and inhibition of growth and
      migration. Our previous data suggest a complex role of syndecan-1 in mesothelioma
      cell proliferation although the exact underlying molecular mechanisms are not
      completely elucidated. The aim of this study is therefore to disclose critical
      genes and pathways affected by syndecan-1 in mesothelioma; in order to better
      understand its importance for tumor cell growth and proliferation. We modulated
      the expression of syndecan-1 in a human mesothelioma cell line via both
      overexpression and silencing, and followed the transcriptomic responses with
      microarray analysis. To project the transcriptome analysis on the full
      dimensional picture of cellular regulation, we applied pathway analysis using
      Ingenuity Pathway Analysis (IPA) and a novel method of network enrichment
      analysis (NEA) which elucidated signaling relations between differentially
      expressed genes and pathways acting via various molecular mechanisms. Syndecan-1
      overexpression had profound effects on genes involved in regulation of cell
      growth, cell cycle progression, adhesion, migration and extracellular matrix
      organization. In particular, expression of several growth factors, interleukins,
      and enzymes of importance for heparan sulfate sulfation pattern, extracellular
      matrix proteins and proteoglycans were significantly altered. Syndecan-1
      silencing had less powerful effect on the transcriptome compared to
      overexpression, which can be explained by the already low initial syndecan-1
      level of these cells. Nevertheless, 14 genes showed response to both up- and
      downregulation of syndecan-1. The "cytokine - cytokine-receptor interaction", the
      TGF-beta, EGF, VEGF and ERK/MAPK pathways were enriched in both experimental
      settings. Most strikingly, nearly all analyzed pathways related to cell cycle
      were enriched after syndecan-1 silencing and depleted after syndecan-1
      overexpression. Syndecan-1 regulates proliferation in a highly complex way,
      although the exact contribution of the altered pathways necessitates further
      functional studies.

PMID- 23144731
TI  - Statins and hip fracture prevention--a population based cohort study in women.
AB  - OBJECTIVE: To study the association of long-term statin use and the risk of low
      energy hip fractures in middle-aged and elderly women. DESIGN: A register-based
      cohort study. SETTING: Finland. PARTICIPANTS: Women aged 45-75 years initiating
      statin therapy between 1996 and 2001 with adherence to statins >= 80% during the
      subsequent five years (n = 40,254), a respective cohort initiating hypertension
      drugs (n = 41 610), and women randomly selected from the population (n = 62 585).
      MAIN OUTCOME MEASURES: Incidence rate of and hazard ratio (HR) for low-energy hip
      fracture during the follow-up extending up to 7 years after the 5-year exposure
      period. RESULTS: Altogether 199 low-energy hip fractures occurred during the 135
      330 person-years (py) of follow-up in the statin cohort, giving an incidence rate
      of 1.5 hip fractures per 1000 py. In the hypertension and the population cohorts,
      the rates were 2.0 per 1000 py (312 fractures per 157,090 py) and 1.0 per 1000 py
      (212 fractures per 216 329 py), respectively. Adjusting for a propensity score
      and individual variables strongly predicting the outcome, good adherence to
      statins for five years was associated with a 29% decreased risk (HR 0.71; 95% CI
      0.58-0.86) of a low-energy hip fracture in comparison with adherent use of
      hypertension drugs. The association was of the same magnitude when comparing the
      statin users with the population cohort, the HR being 0.69 (0.55-0.87). When
      women with poor (<40%), moderate (40 to 80%), and good adherence (>= 80%) to
      statins were compared to those with good adherence to hypertension drugs (>= 80%)
      or to the population cohort, the protective effect associated with statin use
      attenuated with the decreasing level of adherence. CONCLUSIONS: 5-year exposure
      to statins is associated with a reduced risk of low-energy hip fracture in women
      aged 50-80 years without prior hospitalizations for fractures.

PMID- 23144732
TI  - The spectrum of cancers in West Africa: associations with human immunodeficiency
      virus.
AB  - BACKGROUND: Cancer is a growing co-morbidity among HIV-infected patients
      worldwide. With the scale-up of antiretroviral therapy (ART) in developing
      countries, cancer will contribute more and more to the HIV/AIDS disease burden.
      Our objective was to estimate the association between HIV infection and selected
      types of cancers among patients hospitalized for diagnosis or treatment of cancer
      in West Africa. METHODS: A case-referent study was conducted in referral
      hospitals in Cote d'Ivoire and Benin. Each participating clinical ward enrolled
      all adult patients seeking care for a confirmed diagnosis of cancer and
      clinicians systematically proposed an HIV test. HIV prevalence was compared
      between AIDS-defining cancers and a subset of selected non-AIDS defining cancers
      to a referent group of non-AIDS defining cancers not reported in the literature
      to be positively or inversely associated with HIV. An unconditional logistic
      model was used to estimate odds ratios (OR) and their 95% confidence intervals
      (CI) of the risk of being HIV-infected for selected cancers sites compared to a
      referent group of other cancers. RESULTS: The HIV overall prevalence was 12.3%
      (CI 10.3-14.4) among the 1,017 cancer cases included. A total of 442 patients
      constituted the referent group with an HIV prevalence of 4.7% (CI 2.8-6.7). In
      multivariate analysis, Kaposi sarcoma (OR 62.2 [CI 22.1-175.5]), non-Hodgkin
      lymphoma (4.0 [CI 2.0-8.0]), cervical cancer (OR 7.9 [CI 3.8-16.7]), anogenital
      cancer (OR 11.6 [CI 2.9-46.3]) and liver cancer (OR 2.7 [CI 1.1-7.7]) were all
      associated with HIV infection. CONCLUSIONS: In a time of expanding access to ART,
      AIDS-defining cancers remain highly associated with HIV infection. This is to our
      knowledge, the first study reporting a significant association between HIV
      infection and liver cancer in sub-Saharan Africa.

PMID- 23144733
TI  - Identification and structural characterization of a new three-finger toxin
      hemachatoxin from Hemachatus haemachatus venom.
AB  - Snake venoms are rich sources of biologically active proteins and polypeptides.
      Three-finger toxins are non-enzymatic proteins present in elapid (cobras, kraits,
      mambas and sea snakes) and colubrid venoms. These proteins contain four conserved
      disulfide bonds in the core to maintain the three-finger folds. Although all
      three-finger toxins have similar fold, their biological activities are different.
      A new three-finger toxin (hemachatoxin) was isolated from Hemachatus haemachatus
      (Ringhals cobra) venom. Its amino acid sequence was elucidated, and crystal
      structure was determined at 2.43 A resolution. The overall fold is similar to
      other three-finger toxins. The structure and sequence analysis revealed that the
      fold is maintained by four highly conserved disulfide bonds. It exhibited highest
      similarity to particularly P-type cardiotoxins that are known to associate and
      perturb the membrane surface with their lipid binding sites. Also, the increased
      B value of hemachotoxin loop II suggests that loop II is flexible and may remain
      flexible until its interaction with membrane phospholipids. Based on the
      analysis, we predict hemachatoxin to be cardiotoxic/cytotoxic and our future
      experiments will be directed to characterize the activity of hemachatoxin.

PMID- 23144734
TI  - African perceptions of female attractiveness.
AB  - Little is known about mate choice preferences outside Western, educated,
      industrialised, rich and democratic societies, even though these Western
      populations may be particularly unrepresentative of human populations. To our
      knowledge, this is the first study to test which facial cues contribute to
      African perceptions of African female attractiveness and also the first study to
      test the combined role of facial adiposity, skin colour (lightness, yellowness
      and redness), skin homogeneity and youthfulness in the facial attractiveness
      preferences of any population. Results show that youthfulness, skin colour, skin
      homogeneity and facial adiposity significantly and independently predict
      attractiveness in female African faces. Younger, thinner women with a lighter,
      yellower skin colour and a more homogenous skin tone are considered more
      attractive. These findings provide a more global perspective on human mate choice
      and point to a universal role for these four facial cues in female facial
      attractiveness.

PMID- 23144735
TI  - Host-seeking activity of bluetongue virus vectors: endo/exophagy and circadian
      rhythm of Culicoides in Western Europe.
AB  - Feeding success of free-living hematophagous insects depends on their ability to
      be active when hosts are available and to reach places where hosts are
      accessible. When the hematophagous insect is a vector of pathogens, determining
      the components of host-seeking behavior is of primary interest for the assessment
      of transmission risk. Our aim was to describe endo/exophagy and circadian host
      seeking activity of Palaearctic Culicoides species, which are major biting pests
      and arbovirus vectors, using drop traps and suction traps baited with four sheep,
      as bluetongue virus hosts. Collections were carried out in the field, a largely
      open stable and an enclosed stable during six collection periods of 24 hours in
      April/May, in late June and in September/October 2010 in western France. A total
      of 986 Culicoides belonging to 13 species, mainly C. brunnicans and C. obsoletus,
      was collected on animal baits. Culicoides brunnicans was clearly exophagic,
      whereas C. obsoletus was able to enter stables. Culicoides brunnicans exhibited a
      bimodal pattern of host-seeking activity with peaks just after sunrise and
      sunset. Culicoides obsoletus was active before sunset in spring and autumn and
      after sunset in summer, thus illustrating influence of other parameters than
      light, especially temperature. Description of host-seeking behaviors allowed us
      to discuss control strategies for transmission of Culicoides-borne pathogens,
      such as bluetongue virus. However, practical vector-control recommendations are
      difficult to provide because of the variation in the degree of endophagy and time
      of host-seeking activity.

PMID- 23144736
TI  - Rule for scaling shoulder rotation angles while walking through apertures.
AB  - BACKGROUND: When an individual is trying to fit into a narrow aperture, the
      amplitude of shoulder rotations in the yaw dimension is well proportioned to the
      relative aperture width to body width (referred to as the critical ratio value).
      Based on this fact, it is generally considered that the central nervous system
      (CNS) determines the amplitudes of shoulder rotations in response to the ratio
      value. The present study was designed to determine whether the CNS follows
      another rule in which a minimal spatial margin is created at the aperture
      passage; this rule is beneficial particularly when spatial requirements for
      passage (i.e., the minimum passable width) become wider than the body with an
      external object. METHODOLOGY/PRINCIPAL FINDINGS: Eight young participants walked
      through narrow apertures of three widths (ratio value = 0.9, 1.0, and 1.1) while
      holding one of three horizontal bars (short, 1.5 and 2.5 times the body width).
      The results showed that the amplitude of rotation angles became smaller for the
      respective ratio value as the bar increased in length. This was clearly
      inconsistent with the general hypothesis that predicted the same rotation angles
      for the same ratio value. Instead, the results were better explained with a new
      hypothesis which predicted that a smaller rotation angle was sufficient to
      produce a constant spatial margin as the bar-length increased in length.
      CONCLUSION: The results show that, at least under safe circumstances, the CNS is
      likely to determine the amplitudes of shoulder rotations to ensure the minimal
      spatial margin being created at one side of the body at the time of crossing.
      This was new in that the aperture width subtracted from the width of the body
      (plus object) was taken into account for the visuomotor control of locomotion
      through apertures.

PMID- 23144737
TI  - Splenic red pulp macrophages produce type I interferons as early sentinels of
      malaria infection but are dispensable for control.
AB  - Type I interferons (T1IFNs) are among the earliest cytokines produced during
      infections due to their direct regulation by innate immune signaling pathways.
      Reports have suggested that T1IFNs are produced during malaria infection, but
      little is known about the in vivo cellular origins of T1IFNs or their role in
      protection. We have found that in addition to plasmacytoid dendritic cells,
      splenic red pulp macrophages (RPMs) can generate significant quantities of T1IFNs
      in response to P. chabaudi infection in a TLR9-, MYD88-, and IRF7-dependent
      manner. Furthermore, T1IFNs regulate expression of interferon-stimulated genes
      redundantly with Interferon-gamma (IFNG), resulting in redundancy for resistance
      to experimental malaria infection. Despite their role in sensing and promoting
      immune responses to infection, we observe that RPMs are dispensable for control
      of parasitemia. Our results reveal that RPMs are early sentinels of malaria
      infection, but that effector mechanisms previously attributed to RPMs are not
      essential for control.

PMID- 23144739
TI  - Inactivation of Wolbachia reveals its biological roles in whitefly host.
AB  - BACKGROUND: The whitefly Bemisia tabaci is cryptic species complex composed of
      numerous species. Individual species from the complex harbor a diversity of
      bacterial endosymbionts including Wolbachia. However, while Wolbachia is known to
      have a number of different roles, its role in B. tabaci is unclear. Here, the
      antibiotic rifampicin is used to selectively eliminate Wolbachia from B. tabaci
      so as to enable its roles in whitefly development and reproduction to be
      explored. The indirect effects of Wolbachia elimination on the biology of
      Encarsia bimaculata, a dominant parasitoid of B. tabaci in South China, were also
      investigated. METHODOLOGY/PRINCIPAL FINDING: qRT-PCR and FISH were used to show
      that after 48 h exposure to 1.0 mg/ml rifampicin, Wolbachia was completely
      inactivated from B. tabaci Mediterranean (MED) without any significant impact on
      either the primary symbiont, Portiera aleyrodidarum or any of the other secondary
      endosymbionts present. For B. tabaci MED, Wolbachia was shown to be associated
      with decreased juvenile development time, increased likelihood that nymphs
      completed development, increased adult life span and increased percentage of
      female progeny. Inactivation was associated with a significant decrease in the
      body size of the 4(th) instar which leads us to speculate as to whether Wolbachia
      may have a nutrient supplementation role. The reduction in nymph body size has
      consequences for its parasitoid, E. bimaculata. The elimination of Wolbachia lead
      to a marked increase in the proportion of parasitoid eggs that completed their
      development, but the reduced size of the whitefly host was also associated with a
      significant reduction in the size of the emerging parasitoid adult and this was
      in turn associated with a marked reduction in adult parasitoid longevity.
      CONCLUSIONS/SIGNIFICANCE: Wolbachia increases the fitness of the whitefly host
      and provides some protection against parasitization. These observations add to
      our understanding of the roles played by bacterial endosymbionts.

PMID- 23144740
TI  - Comparative performance of electrochemiluminescence immunoassay and EIA for HIV
      screening in a multiethnic region of China.
AB  - BACKGROUND: The recent approval of 4th generation HIV tests has forced many
      laboratories to decide whether to shift from 3rd to these tests. There are
      limited published studies on the comparative evaluation of these two different
      assays. We compare the performance of fourth-generation electrochemiluminescence
      immunoassay (ChIA) and third-generation enzyme linked immunosorbent assay (EIA)
      for human immunodeficiency virus (HIV) screening and gauge whether the shift from
      EIA to ChIA could be better in a multiethnic region of China.
      METHODOLOGY/PRINCIPAL FINDINGS: We identified a large number of routine specimens
      (345,492) using two different assays from Jan 2008 to Aug 2011 in a teaching
      hospital with high sample throughput. Of the 344,596 specimens with interpretable
      HIV test results, 526(0.23%) of 228,761 using EIA and 303(0.26%) of 115,835 using
      ChIA were HIV-1 positive. The false-positive rate of EIA was lower than that of
      ChIA [0.03% vs. 0.08%, odds ratio 0.33 (95% confidence interval 0.24, 0.45)]. The
      positive predictive value (PPV) of EIA (89.6%) was significantly higher than that
      of ChIA (76.1%) (<0.001), reflecting the difference between the two assays. The
      clinical sensitivities of two assays in this study were 99.64% for EIA and 99.88%
      for ChIA. CONCLUSION: Caution is needed before shifting from 3rd to 4th
      generation HIV tests. Since none of these tests are perfect, different geographic
      and ethnic area probably require different considerations with regard to HIV
      testing methods, taking into account the local conditions.

PMID- 23144738
TI  - AP-3 and Rabip4' coordinately regulate spatial distribution of lysosomes.
AB  - The RUN and FYVE domain proteins rabip4 and rabip4' are encoded by RUFY1 and
      differ in a 108 amino acid N-terminal extension in rabip4'. Their identical C
      terminus binds rab5 and rab4, but the function of rabip4s is incompletely
      understood. We here found that silencing RUFY1 gene products promoted outgrowth
      of plasma membrane protrusions, and polarized distribution and clustering of
      lysosomes at their tips. An interactor screen for proteins that function together
      with rabip4' yielded the adaptor protein complex AP-3, of which the hinge region
      in the beta3 subunit bound directly to the FYVE domain of rabip4'. Rabip4'
      colocalized with AP-3 on a tubular subdomain of early endosomes and the extent of
      colocalization was increased by a dominant negative rab4 mutant. Knock-down of AP
      3 had an ever more dramatic effect and caused accumulation of lysosomes in
      protrusions at the plasma membrane. The most peripheral lysosomes were localized
      beyond microtubules, within the cortical actin network. Our results uncover a
      novel function for AP-3 and rabip4' in regulating lysosome positioning through an
      interorganellar pathway.

PMID- 23144741
TI  - Potentiation of thrombin generation in hemophilia A plasma by coagulation factor
      VIII and characterization of antibody-specific inhibition.
AB  - Development of inhibitory antibodies to coagulation factor VIII (fVIII) is the
      primary obstacle to the treatment of hemophilia A in the developed world. This
      adverse reaction occurs in 20-30% of persons with severe hemophilia A treated
      with fVIII-replacement products and is characterized by the development of a
      humoral and neutralizing immune response to fVIII. Patients with inhibitory anti
      fVIII antibodies are treated with bypassing agents including recombinant factor
      VIIa (rfVIIa). However, some patients display poor hemostatic response to bypass
      therapy and improved treatment options are needed. Recently, we demonstrated that
      fVIII inhibitors display widely variable kinetics of inhibition that correlate
      with their respective target epitopes. Thus, it was hypothesized that for
      antibodies that display slow rates of inhibition, supplementation of rfVIIa with
      fVIII would result in improved thrombin generation and be predictive of clinical
      responses to this novel treatment regimen. In order to test this hypothesis, 10
      murine monoclonal antibodies (MAbs) with non-overlapping epitopes spanning fVIII,
      differential inhibition titers, and inhibition kinetics were studied using a
      thrombin generation assay. Of the 3 MAbs with high inhibitory titers, only the
      one with fast and complete (classically defined as "type I") kinetics displayed
      significant inhibition of thrombin generation with no improvement upon
      supplementation of rfVIIa with fVIII. The other two MAbs that displayed
      incomplete (classically defined as "type II") inhibition did not suppress the
      potentiation of thrombin generation by fVIII. All antibodies that did not
      completely inhibit fVIII activity demonstrated potentiation of thrombin
      generation by the addition of fVIII as compared to rfVIIa alone. In conclusion,
      fVIII alone or in combination with rfVIIa corrects the thrombin generation defect
      produced by the majority of anti-fVIII MAbs better than single agent rfVIIa.
      Therefore, combined fVIII/rfVIIa therapy may provide better hemostatic control
      than current therapy in some patients with anti-fVIII inhibitors.

PMID- 23144742
TI  - The effect of ratio and interval training on Pavlovian-instrumental transfer in
      mice.
AB  - Conditional stimuli (CS) that are paired with reward can be used to motivate
      instrumental responses. This process is called Pavlovian-instrumental transfer
      (PIT). A recent study in rats suggested that habitual responses are particularly
      sensitive to the motivational effects of reward cues. The current experiments
      examined this idea using ratio and interval training in mice. Two groups of
      animals were trained to lever press for food pellets that were delivered on
      random ratio or random interval schedules. Devaluation tests revealed that
      interval training led to habitual responding while ratio training produced goal
      directed actions. The presentation of CSs paired with reward led to positive
      transfer in both groups, however, the size of this effect was much larger in mice
      that were trained on interval schedules. This result suggests that habitual
      responses are more sensitive to the motivational influence of reward cues than
      goal-directed actions. The implications for neurobiological models of motivation
      and drug seeking behaviors are discussed.

PMID- 23144743
TI  - SH2D2A modulates T cell mediated protection to a B cell derived tumor in
      transgenic mice.
AB  - BACKGROUND: T cell specific adapter protein (TSAd), encoded by the SH2D2A gene,
      modulates signaling downstream of the T cell receptor (TCR). Young, unchallenged
      SH2D2A-deficient C57BL/6 mice exhibit a relatively normal immune phenotype. To
      address whether SH2D2A regulates physiologic immune responses, SH2D2A-deficient
      TCR-transgenic BALB/c mice were generated. The transgenic TCR recognizes a
      myeloma-derived idiotypic (Id) peptide in the context of the major
      histocompatibility complex (MHC) class II molecule I-E(d), and confers T cell
      mediated resistance to transplanted multiple myeloma development in vivo.
      PRINCIPAL FINDINGS: The immune phenotype of SH2D2A-deficient C57BL/6 and BALB/c
      mice did not reveal major differences compared to the corresponding wild type
      mice. When challenged with myeloma cells, Id-specific TCR-transgenic BALB/c mice
      lacking SH2D2A displayed increased resistance towards tumor development. Tumor
      free TCR-transgenic SH2D2A-deficient mice had higher numbers of Id-specific
      single positive CD4+ thymocytes compared to TCR-transgenic wild-type mice.
      CONCLUSION: Our results suggest a modulatory role for SH2D2A in T cell mediated
      immune surveillance of cancer. However, it remains to be established whether its
      effect is T-cell intrinsic. Further studies are required to determine whether
      targeting SH2D2A function in T cells may be a potential adjuvant in cancer
      immunotherapy.

PMID- 23144744
TI  - Annexin A1 induces skeletal muscle cell migration acting through formyl peptide
      receptors.
AB  - Annexin A1 (ANXA1, lipocortin-1) is a glucocorticoid-regulated 37-kDa protein, so
      called since its main property is to bind (i.e. to annex) to cellular membranes
      in a Ca(2+)-dependent manner. Although ANXA1 has predominantly been studied in
      the context of immune responses and cancer, the protein can affect a larger
      variety of biological phenomena, including cell proliferation and migration. Our
      previous results show that endogenous ANXA1 positively modulates myoblast cell
      differentiation by promoting migration of satellite cells and, consequently,
      skeletal muscle differentiation. In this work, we have evaluated the hypothesis
      that ANXA1 is able to exert effects on myoblast cell migration acting through
      formyl peptide receptors (FPRs) following changes in its subcellular localization
      as in other cell types and tissues. The analysis of the subcellular localization
      of ANXA1 in C2C12 myoblasts during myogenic differentiation showed an interesting
      increase of extracellular ANXA1 starting from the initial phases of skeletal
      muscle cell differentiation. The investigation of intracellular Ca(2+)
      perturbation following exogenous administration of the ANXA1 N-terminal derived
      peptide Ac2-26 established the engagement of the FPRs which expression in C2C12
      cells was assessed by qualitative PCR. Wound healing assay experiments showed
      that Ac2-26 peptide is able to increase migration of C2C12 skeletal muscle cells
      and to induce cell surface translocation and secretion of ANXA1. Our results
      suggest a role for ANXA1 as a highly versatile component in the signaling chains
      triggered by the proper calcium perturbation that takes place during active
      migration and differentiation or membrane repair since the protein is strongly
      redistributed onto the plasma membranes after an rapid increase of intracellular
      levels of Ca(2+). These properties indicate that ANXA1 may be involved in a novel
      repair mechanism for skeletal muscle and may have therapeutic implications with
      respect to the development of ANXA1 mimetics.

PMID- 23144745
TI  - Increased serum hepcidin levels in subjects with the metabolic syndrome: a
      population study.
AB  - The recent discovery of hepcidin, the key iron regulatory hormone, has changed
      our view of iron metabolism, which in turn is long known to be linked with
      insulin resistant states, including type 2 diabetes mellitus and the Metabolic
      Syndrome (MetS). Serum ferritin levels are often elevated in MetS (Dysmetabolic
      hyperferritinemia--DHF), and are sometimes associated with a true mild-to
      moderate hepatic iron overload (dysmetabolic iron overload syndrome--DIOS).
      However, the pathophysiological link between iron and MetS remains unclear. This
      study was aimed to investigate, for the first time, the relationship between MetS
      and hepcidin at population level. We measured serum hepcidin levels by Mass
      Spectrometry in 1,391 subjects from the Val Borbera population, and evaluated
      their relationship with classical MetS features. Hepcidin levels increased
      significantly and linearly with increasing number of MetS features, paralleling
      the trend of serum ferritin. In multivariate models adjusted for relevant
      variables including age, C-Reactive Protein, and the HFE C282Y mutation, ferritin
      was the only significant independent predictor of hepcidin in males, while in
      females MetS was also independently associated with hepcidin. Overall, these data
      indicate that the fundamental iron regulatory feedback is preserved in MetS, i.e.
      that hepcidin tends to progressively increase in response to the increase of iron
      stores. Due to recently discovered pleiotropic effects of hepcidin, this may
      worsen insulin resistance and contribute to the cardiovascular complications of
      MetS.

PMID- 23144746
TI  - Climate change, population immunity, and hyperendemicity in the transmission
      threshold of dengue.
AB  - BACKGROUND: It has been suggested that the probability of dengue epidemics could
      increase because of climate change. The probability of epidemics is most commonly
      evaluated by the basic reproductive number (R(0)), and in mosquito-borne
      diseases, mosquito density (the number of female mosquitoes per person [MPP]) is
      the critical determinant of the R(0) value. In dengue-endemic areas, 4 different
      serotypes of dengue virus coexist-a state known as hyperendemicity-and a certain
      proportion of the population is immune to one or more of these serotypes.
      Nevertheless, these factors are not included in the calculation of R(0). We aimed
      to investigate the effects of temperature change, population immunity, and
      hyperendemicity on the threshold MPP that triggers an epidemic. METHODS AND
      FINDINGS: We designed a mathematical model of dengue transmission dynamics. An
      epidemic was defined as a 10% increase in seroprevalence in a year, and the MPP
      that triggered an epidemic was defined as the threshold MPP. Simulations were
      conducted in Singapore based on the recorded temperatures from 1980 to 2009 The
      threshold MPP was estimated with the effect of (1) temperature only; (2)
      temperature and fluctuation of population immunity; and (3) temperature,
      fluctuation of immunity, and hyperendemicity. When only the effect of temperature
      was considered, the threshold MPP was estimated to be 0.53 in the 1980s and 0.46
      in the 2000s, a decrease of 13.2%. When the fluctuation of population immunity
      and hyperendemicity were considered in the model, the threshold MPP decreased by
      38.7%, from 0.93 to 0.57, from the 1980s to the 2000s. CONCLUSIONS: The threshold
      MPP was underestimated if population immunity was not considered and
      overestimated if hyperendemicity was not included in the simulations. In addition
      to temperature, these factors are particularly important when quantifying the
      threshold MPP for the purpose of setting goals for vector control in dengue
      endemic areas.

PMID- 23144747
TI  - Prediction of C. elegans longevity genes by human and worm longevity networks.
AB  - Intricate and interconnected pathways modulate longevity, but screens to identify
      the components of these pathways have not been saturating. Because biological
      processes are often executed by protein complexes and fine-tuned by regulatory
      factors, the first-order protein-protein interactors of known longevity genes are
      likely to participate in the regulation of longevity. Data-rich maps of protein
      interactions have been established for many cardinal organisms such as yeast,
      worms, and humans. We propose that these interaction maps could be mined for the
      identification of new putative regulators of longevity. For this purpose, we have
      constructed longevity networks in both humans and worms. We reasoned that the
      essential first-order interactors of known longevity-associated genes in these
      networks are more likely to have longevity phenotypes than randomly chosen genes.
      We have used C. elegans to determine whether post-developmental inactivation of
      these essential genes modulates lifespan. Our results suggest that the worm and
      human longevity networks are functionally relevant and possess a high predictive
      power for identifying new longevity regulators.

PMID- 23144748
TI  - Mutational bias and translational selection shaping the codon usage pattern of
      tissue-specific genes in rice.
AB  - The regulatory mechanisms of determining which genes specifically expressed in
      which tissues are still not fully elucidated, especially in plants. Using
      internal correspondence analysis, I first establish that tissue-specific genes
      exhibit significantly different synonymous codon usage in rice, although this
      effect is weak. The variability of synonymous codon usage between tissues
      accounts for 5.62% of the total codon usage variability, which has mainly arisen
      from the neutral evolutionary forces, such as GC content variation among tissues.
      Moreover, tissue-specific genes are under differential selective constraints,
      inferring that natural selection also contributes to the codon usage divergence
      between tissues. These findings may add further evidence in understanding the
      differentiation and regulation of tissue-specific gene products in plants.

PMID- 23144749
TI  - Forkhead transcription factor FOXP3 upregulates CD25 expression through
      cooperation with RelA/NF-kappaB.
AB  - Considerable evidence supports the prediction that CD25 is directly regulated by
      the forkhead transcription factor FOXP3. However, given that CD25 is normally
      upregulated in activated T cells, regardless of whether they express FOXP3, this
      issue has still to be definitively demonstrated. Here we describe that FOXP3,
      induced by CD28 signals in human CD4(+)CD25(-) T lymphocytes, synergizes with
      RelA on a regulatory region of Cd25 promoter to mediate the transcriptional
      activation of Cd25 gene. We found that a striking feature of this regulatory
      region is the presence of a kappaB site and of two tandem copies of a non
      consensus FOXP3 binding site separated at 5' ends by 19 nucleotides that allow
      FOXP3 and RelA binding to DNA and their physical interaction. The occupancy of
      the two FOXP3 binding sites in conjunction with RelA binding site occupancy
      allows FOXP3 to function as a positive activator of Cd25 gene. Indeed mutations
      of both FOXP3 binding sites such as mutation of kappaB site on Cd25 promoter
      abolished FOXP3 activatory functions. Moreover, FOXP3 mutation DeltaE251, that
      compromises FOXP3 homotypic interactions, failed to trans activate Cd25 promoter,
      suggesting that both FOXP3 DNA binding and dimerization are required to trans
      activate Cd25 promoter. These findings identify a novel mechanism by which RelA
      and FOXP3 cooperate to mediate transcriptional regulation of target genes and
      characterize a region on Cd25 promoter where FOXP3 dimer could bridge
      intramolecularly two DNA sites and trans activate Cd25 gene.

PMID- 23144750
TI  - Protective antibody and CD8+ T-cell responses to the Plasmodium falciparum
      circumsporozoite protein induced by a nanoparticle vaccine.
AB  - BACKGROUND: The worldwide burden of malaria remains a major public health problem
      due, in part, to the lack of an effective vaccine against the Plasmodium
      falciparum parasite. An effective vaccine will most likely require the induction
      of antigen specific CD8(+) and CD4(+) T-cells as well as long-lasting antibody
      responses all working in concert to eliminate the infection. We report here the
      effective modification of a self-assembling protein nanoparticle (SAPN) vaccine
      previously proven effective in control of a P. berghei infection in a rodent
      model to now present B- and T-cell epitopes of the human malaria parasite P.
      falciparum in a platform capable of being used in human subjects.
      METHODOLOGY/PRINCIPAL FINDINGS: To establish the basis for a SAPN-based vaccine,
      B- and CD8(+) T-cell epitopes from the P. falciparum circumsporozoite protein
      (PfCSP) and the universal CD4 T-helper epitope PADRE were engineered into a
      versatile small protein (~125 amino acids) that self-assembles into a spherical
      nanoparticle repetitively displaying the selected epitopes. P. falciparum epitope
      specific immune responses were evaluated in mice using a transgenic P. berghei
      malaria parasite of mice expressing the human malaria full-length P. falciparum
      circumsporozoite protein (Tg-Pb/PfCSP). We show that SAPN constructs, delivered
      in saline, can induce high-titer, long-lasting (1 year) protective antibody and
      poly-functional (IFNgamma(+), IL-2(+)) long-lived central memory CD8(+) T-cells.
      Furthermore, we demonstrated that these Ab or CD8(+) T-cells can independently
      provide sterile protection against a lethal challenge of the transgenic
      parasites. CONCLUSION: The SAPN construct induces long-lasting antibody and
      cellular immune responses to epitope specific sequences of the P. falciparum
      circumsporozoite protein (PfCSP) and prevents infection in mice by a transgenic
      P. berghei parasite displaying the full length PfCSP.

PMID- 23144751
TI  - Dose-related estrogen effects on gene expression in fetal mouse prostate
      mesenchymal cells.
AB  - Developmental exposure of mouse fetuses to estrogens results in dose-dependent
      permanent effects on prostate morphology and function. Fetal prostatic mesenchyme
      cells express estrogen receptor alpha (ERalpha) and androgen receptors and
      convert stimuli from circulating estrogens and androgens into paracrine signaling
      to regulate epithelial cell proliferation and differentiation. To obtain
      mechanistic insight into the role of different doses of estradiol (E2) in
      regulating mesenchymal cells, we examined E2-induced transcriptomal changes in
      primary cultures of fetal mouse prostate mesenchymal cells. Urogenital sinus
      mesenchyme cells were obtained from male mouse fetuses at gestation day 17 and
      exposed to 10 pM, 100 pM or 100 nM E2 in the presence of a physiological
      concentration of dihydrotestosterone (0.69 nM) for four days. Gene ontology
      studies suggested that low doses of E2 (10 pM and 100 pM) induce genes involved
      in morphological tissue development and sterol biosynthesis but suppress genes
      involved in growth factor signaling. Genes involved in cell adhesion were
      enriched among both up-regulated and down-regulated genes. Genes showing inverted
      U-shape dose responses (enhanced by E2 at 10 pM E2 but suppressed at 100 pM) were
      enriched in the glycolytic pathway. At the highest dose (100 nM), E2 induced
      genes enriched for cell adhesion, steroid hormone signaling and metabolism,
      cytokines and their receptors, cell-to-cell communication, Wnt signaling, and TGF
      beta signaling. These results suggest that prostate mesenchymal cells may
      regulate epithelial cells through direct cell contacts when estrogen level is low
      whereas secreted growth factors and cytokines might play significant roles when
      estrogen level is high.

PMID- 23144752
TI  - Effects of the oral administration of viable and heat-killed Streptococcus bovis
      HC5 cells to pre-sensitized BALB/c mice.
AB  - Antimicrobial peptides have been suggested as an alternative to classical
      antibiotics in livestock production and bacteriocin-producing bacteria could be
      added to animal feeds to deliver bacteriocins in the gastrointestinal (GI) tract
      of ruminant and monogastric animals. In this study, viable (V) and heat-killed
      (HK) Streptococcus bovis HC5 cells were orally administered to pre-sensitized
      mice in order to assess the effects of a bacteriocin-producing bacteria on
      histological parameters and the immune response of the GI tract of monogastric
      animals. The administration of V and HK S. bovis HC5 cells during 58 days to
      BALB/c mice did not affect weight gain, but an increase in gut permeability was
      detected in animals receiving the HK cells. Viable and heat killed cells caused
      similar morphological alterations in the GI tract of the animals, but the most
      prominent effects were detected in the small intestine. The oral administration
      of S. bovis HC5 also influenced cytokine production in the small intestine, and
      the immune-mediated activity differed between V and HK cells. The relative
      expression of IL-12 and INF-gamma was significantly higher in the small intestine
      of mice treated with V cells, while an increase in IL-5, IL-13 and TNF-alpha
      expression was only detected in mice treated with HK cells. Considering that even
      under a condition of severe challenge (pre-sensitization followed by daily
      exposure to the same bacterial immunogen) the general health of the animals was
      maintained, it appears that oral administration of S. bovis HC5 cells could be a
      useful route to deliver bacteriocin in the GI tract of livestock animals.

PMID- 23144753
TI  - A streamlined method for detecting structural variants in cancer genomes by short
      read paired-end sequencing.
AB  - Defining the architecture of a specific cancer genome, including its structural
      variants, is essential for understanding tumor biology, mechanisms of
      oncogenesis, and for designing effective personalized therapies. Short read
      paired-end sequencing is currently the most sensitive method for detecting
      somatic mutations that arise during tumor development. However, mapping
      structural variants using this method leads to a large number of false positive
      calls, mostly due to the repetitive nature of the genome and the difficulty of
      assigning correct mapping positions to short reads. This study describes a method
      to efficiently identify large tumor-specific deletions, inversions, duplications
      and translocations from low coverage data using SVDetect or BreakDancer software
      and a set of novel filtering procedures designed to reduce false positive calls.
      Applying our method to a spontaneous T cell lymphoma arising in a core RAG2/p53
      deficient mouse, we identified 40 validated tumor-specific structural
      rearrangements supported by as few as 2 independent read pairs.

PMID- 23144754
TI  - Microdistribution of faunal assemblages at deep-sea hydrothermal vents in the
      Southern Ocean.
AB  - Chemosynthetic primary production by microbes supports abundant faunal
      assemblages at deep-sea hydrothermal vents, with zonation of invertebrate species
      typically occurring along physico-chemical gradients. Recently discovered vent
      fields on the East Scotia Ridge (ESR) in the Southern Ocean represent a new
      province of vent biogeography, but the spatial dynamics of their distinct fauna
      have yet to be elucidated. This study determines patterns of faunal zonation,
      species associations, and relationships between faunal microdistribution and
      hydrothermal activity in a vent field at a depth of 2,400 m on the ESR. Remotely
      operated vehicle (ROV) dives obtained high-definition imagery of three chimney
      structures with varying levels of hydrothermal activity, and a mosaic image of
      >250 m(2) of seafloor co-registered with temperature measurements. Analysis of
      faunal microdistribution within the mosaiced seafloor reveals a consistent
      pattern of faunal zonation with increasing distance from vent sources and peak
      temperatures. Assemblages closest to vent sources are visibly dominated by a new
      species of anomuran crab, Kiwa n. sp. (abundance >700 individuals m(-2)),
      followed by a peltospiroid gastropod (>1,500 individuals m(-2)), eolepadid
      barnacle (>1,500 individuals m(-2)), and carnivorous actinostolid anemone (>30
      individuals m(-2)). Peripheral fauna are not dominated by a single taxon, but
      include predatory and scavenger taxa such as stichasterid seastars, pycnogonids
      and octopus. Variation in faunal microdistribution on chimneys with differing
      levels of activity suggests a possible successional sequence for vent fauna in
      this new biogeographic province. An increase in delta(34)S values of primary
      consumers with distance from vent sources, and variation in their delta(13)C
      values also indicate possible zonation of nutritional modes of the vent fauna. By
      using ROV videography to obtain a high-resolution representation of a vent
      environment over a greater extent than previous studies, these results provide a
      baseline for determining temporal change and investigations of processes
      structuring faunal assemblages at Southern Ocean vents.

PMID- 23144755
TI  - Enrichment of HIV-1 subtype AD recombinants in a Ugandan cohort of severely
      septic patients.
AB  - BACKGROUND: Several population-wide HIV-1 subtype distribution studies in Uganda
      have evaluated relatively healthy clinic patients. Given the differences in HIV-1
      disease progression based on subtype, we examined HIV-1 subtype distribution and
      disease outcomes among hospitalized patients with severe sepsis. METHODS:
      Patients with severe sepsis were enrolled at two hospitals in Uganda. Data
      collected included demographics, Karnofsky scores, highly active antiretroviral
      therapy (HAART) use, HIV-1 serostatus, CD4+ T cell concentration, whole blood
      lactate concentration, and blood cultures. HIV-1 subtypes were determined by
      sequencing parts of the gag and env genes, followed by phylogenetic analysis.
      RESULTS: Of the 267 patients evaluated, 228 (85.4%) were HIV infected. The
      predominant HIV-1 subtypes were A (46%), D (17%), and AD recombinants (30%). HIV
      1 subtypes B, C, and other recombinants were uncommon. Patients infected with HIV
      1 subtypes A, D and AD viruses were similar in demographics, CD4(+) T cell
      concentration, HAART use, Karnofsky scores, whole blood lactate concentration,
      and positive blood cultures. There was no difference in 30-day mortality from
      severe sepsis between the 3 groups (p = 0.99). CONCLUSION: A high proportion of
      HIV-1 subtypes A and AD recombinants was observed in this cohort of severely
      septic patients. The proportion of AD recombinants was higher in this cohort than
      in previous cohorts of Ugandan HIV-1 patients. No difference in baseline
      demographics, clinical factors or 30-day mortality was seen across HIV-subtypes.

PMID- 23144756
TI  - Structural insight into the Clostridium difficile ethanolamine utilisation
      microcompartment.
AB  - Bacterial microcompartments form a protective proteinaceous barrier around
      metabolic enzymes that process unstable or toxic chemical intermediates. The
      genome of the virulent, multidrug-resistant Clostridium difficile 630 strain
      contains an operon, eut, encoding a bacterial microcompartment with genes for the
      breakdown of ethanolamine and its utilisation as a source of reduced nitrogen and
      carbon. The C. difficile eut operon displays regulatory genetic elements and
      protein encoding regions in common with homologous loci found in the genomes of
      other bacteria, including the enteric pathogens Salmonella enterica and
      Enterococcus faecalis. The crystal structures of two microcompartment shell
      proteins, CD1908 and CD1918, and an uncharacterised protein with potential
      enzymatic activity, CD1925, were determined by X-ray crystallography. CD1908 and
      CD1918 display the same protein fold, though the order of secondary structure
      elements is permuted in CD1908 and this protein displays an N-terminal beta
      strand extension. These proteins form hexamers with molecules related by
      crystallographic and non-crystallographic symmetry. The structure of CD1925 has a
      cupin beta-barrel fold and a putative active site that is distinct from the metal
      ion dependent catalytic cupins. Thin-section transmission electron microscopy of
      Escherichia coli over-expressing eut proteins indicates that CD1918 is capable of
      self-association into arrays, suggesting an organisational role for CD1918 in the
      formation of this microcompartment. The work presented provides the basis for
      further study of the architecture and function of the C. difficile eut
      microcompartment, its role in metabolism and the wider consequences of intestinal
      colonisation and virulence in this pathogen.

PMID- 23144757
TI  - Major radiations in the evolution of Caviid rodents: reconciling fossils, ghost
      lineages, and relaxed molecular clocks.
AB  - BACKGROUND: Caviidae is a diverse group of caviomorph rodents that is broadly
      distributed in South America and is divided into three highly divergent extant
      lineages: Caviinae (cavies), Dolichotinae (maras), and Hydrochoerinae
      (capybaras). The fossil record of Caviidae is only abundant and diverse since the
      late Miocene. Caviids belongs to Cavioidea sensu stricto (Cavioidea s.s.) that
      also includes a diverse assemblage of extinct taxa recorded from the late
      Oligocene to the middle Miocene of South America ("eocardiids"). RESULTS: A
      phylogenetic analysis combining morphological and molecular data is presented
      here, evaluating the time of diversification of selected nodes based on the
      calibration of phylogenetic trees with fossil taxa and the use of relaxed
      molecular clocks. This analysis reveals three major phases of diversification in
      the evolutionary history of Cavioidea s.s. The first two phases involve two
      successive radiations of extinct lineages that occurred during the late Oligocene
      and the early Miocene. The third phase consists of the diversification of
      Caviidae. The initial split of caviids is dated as middle Miocene by the fossil
      record. This date falls within the 95% higher probability distribution estimated
      by the relaxed Bayesian molecular clock, although the mean age estimate ages are
      3.5 to 7 Myr older. The initial split of caviids is followed by an obscure period
      of poor fossil record (referred here as the Mayoan gap) and then by the
      appearance of highly differentiated modern lineages of caviids, which
      evidentially occurred at the late Miocene as indicated by both the fossil record
      and molecular clock estimates. CONCLUSIONS: The integrated approach used here
      allowed us identifying the agreements and discrepancies of the fossil record and
      molecular clock estimates on the timing of the major events in cavioid evolution,
      revealing evolutionary patterns that would not have been possible to gather using
      only molecular or paleontological data alone.

PMID- 23144758
TI  - NADPH oxidase 4 mediates insulin-stimulated HIF-1alpha and VEGF expression, and
      angiogenesis in vitro.
AB  - Acute intensive insulin therapy causes a transient worsening of diabetic
      retinopathy in type 1 diabetes patients and is related to VEGF expression.
      Reactive oxygen species (ROS) have been shown to be involved in HIF-1alpha and
      VEGF expression induced by insulin, but the role of specific ROS sources has not
      been fully elucidated. In this study we examined the role of NADPH oxidase
      subunit 4 (Nox4) in insulin-stimulated HIF-1alpha and VEGF expression, and
      angiogenic responses in human microvascular endothelial cells (HMVECs). Here we
      demonstrate that knockdown of Nox4 by siRNA reduced insulin-stimulated ROS
      generation, the tyrosine phosphorylation of IR-beta and IRS-1, but did not change
      the serine phosphorylation of IRS-1. Nox4 gene silencing had a much greater
      inhibitory effect on insulin-induced AKT activation than ERK1/2 activation,
      whereas it had little effect on the expression of the phosphatases such as MKP-1
      and SHIP. Inhibition of Nox4 expression inhibited the transcriptional activity of
      VEGF through HIF-1. Overexpression of wild-type Nox4 was sufficient to increase
      VEGF transcriptional activity, and further enhanced insulin-stimulated the
      activation of VEGF. Downregulation of Nox4 expression decreased insulin
      stimulated mRNA and protein expression of HIF-1alpha, but did not change the rate
      of HIF-1alpha degradation. Inhibition of Nox4 impaired insulin-stimulated VEGF
      expression, cell migration, cell proliferation, and tube formation in HMVECs. Our
      data indicate that Nox4-derived ROS are essential for HIF-1alpha-dependent VEGF
      expression, and angiogenesis in vitro induced by insulin. Nox4 may be an
      attractive therapeutic target for diabetic retinopathy caused by intensive
      insulin treatment.

PMID- 23144759
TI  - Early hemoperfusion may improve survival of severely paraquat-poisoned patients.
AB  - BACKGROUND: Thousands of paraquat (PQ)-poisoned patients continue to die,
      particularly in developing countries. Although animal studies indicate that
      hemoperfusion (HP) within 2-4 h after intoxication effectively reduces mortality,
      the effect of early HP in humans remains unknown. METHODS: We analyzed the
      records of all PQ-poisoned patients admitted to 2 hospitals between 2000 and
      2009. Patients were grouped according to early or late HP and high-dose (oral
      cyclophosphamide [CP] and intravenous dexamethasone [DX]) or repeated pulse
      (intravenous methylprednisolone [MP] and CP, followed by DX and repeated MP
      and/or CP) PQ therapy. Early HP was defined as HP <4 h, and late HP, as HP >= 4 h
      after PQ ingestion. We evaluated the associations between HP <4 h, <5 h, <6 h,
      and <7 h after PQ ingestion and the outcomes. Demographic, clinical, laboratory,
      and mortality data were analyzed. RESULTS: The study included 207 severely PQ
      poisoned patients. Forward stepwise multivariate Cox hazard regression analysis
      showed that early HP <4 h (hazard ratio [HR] = 0.38, 95% confidence interval (CI)
      0.16-0.86; P = 0.020) or HP <5 h (HR = 0.60, 95% CI: 0.39-0.92; P = 0.019)
      significantly decreased the mortality risk. Further analysis showed that early HP
      reduced the mortality risk only in patients treated with repeated pulse therapy
      (n = 136), but not high-dose therapy (n = 71). Forward stepwise multivariate Cox
      hazard regression analysis showed that HP <4.0 h (HR = 0.19, 95% CI: 0.05-0.79; P
      = 0.022) or <5.0 h (HR = 0.49, 95% CI: 0.24-0.98; P = 0.043) after PQ ingestion
      significantly decreased the mortality risk in repeated pulse therapy patients,
      after adjustment for relevant variables. CONCLUSION: The results showed that
      early HP after PQ exposure might be effective in reducing mortality in severely
      poisoned patients, particularly in those treated with repeated pulse therapy.

PMID- 23144760
TI  - Characterization of Nrf1b, a novel isoform of the nuclear factor-erythroid-2
      related transcription factor-1 that activates antioxidant response element
      regulated genes.
AB  - Nuclear factor E2-related factor 1 (Nrf1) is a basic leucine zipper transcription
      factor that plays an important role in the activation of cytoprotective genes
      through the antioxidant response elements. The previously characterized long
      isoform of Nrf1 (Nrf1a) is targeted to the endoplasmic reticulum and accumulates
      in the nucleus in response to activating signals. Here we characterized a novel
      Nrf1 protein isoform (Nrf1b) generated through an alternative promoter and first
      exon that lacks the ER targeting domain of Nrf1a. The 5'-flanking region of Nrf1b
      directed high levels of luciferase reporter expression in cells. RT-PCR and
      Western blotting showed Nrf1b is widely expressed in various cell lines and mouse
      tissues. Immunoblot analysis of subcellular fractions and imaging of green
      fluorescence protein (GFP)-tagged Nrf1b demonstrate Nrf1b is constitutively
      localized to the nucleus. Nrf1b can activate GAL4-dependent transcription when
      fused to the heterologous GAL4 DNA-binding domain. Gel-shift and
      coimmunoprecipitation experiments demonstrate that Nrf1b forms a complex with
      MafG, and expression of Nrf1b activates the expression of antioxidant response
      element containing reporters and genes in cells. These results suggest Nrf1b is
      targeted to the nucleus where it activates ARE-driven genes and may play a role
      in modulating antioxidant response elements.

PMID- 23144762
TI  - Effects of non-indigenous oysters on microbial diversity and ecosystem
      functioning.
AB  - Invasive ecosystem engineers can physically and chemically alter the receiving
      environment, thereby affecting biodiversity and ecosystem functioning. The
      Pacific oyster, Crassostrea gigas, invasive throughout much of the world, can
      establish dense populations monopolising shorelines and possibly altering
      ecosystem processes including decomposition and nutrient cycling. The effects of
      increasing cover of invasive C. gigas on ecosystem processes and associated
      microbial assemblages in mud-flats were tested experimentally in the field. Pore
      water nutrients (NH(4)(+) and total oxidised nitrogen), sediment chlorophyll
      content, microbial activity, total carbon and nitrogen, and community respiration
      (CO(2) and CH(4)) were measured to assess changes in ecosystem functioning.
      Assemblages of bacteria and functionally important microbes, including
      methanogens, methylotrophs and ammonia-oxidisers were assessed in the oxic and
      anoxic layers of sediment using terminal restriction length polymorphism of the
      bacterial 16S rRNA, mxaF, amoA and archaeal mcrA genes respectively. At higher
      covers (40 and 80%) of oysters there was significantly greater microbial
      activity, increased chlorophyll content, CO(2) (13 fold greater) and CH(4) (6
      fold greater) emission from the sediment compared to mud-flats without C. gigas.
      At 10% cover, C. gigas increased the concentration of total oxidised nitrogen and
      altered the assemblage structure of ammonia-oxidisers and methanogens.
      Concentrations of pore-water NH(4)(+) were increased by C. gigas regardless of
      cover. Invasive species can alter ecosystem functioning not only directly, but
      also indirectly, by affecting microbial communities vital for the maintenance of
      ecosystem processes, but the nature and magnitude of these effects can be non
      linear, depending on invader abundance.

PMID- 23144761
TI  - Heme binding proteins of Bartonella henselae are required when undergoing
      oxidative stress during cell and flea invasion.
AB  - Bartonella are hemotropic bacteria responsible for emerging zoonoses. These heme
      auxotroph alphaproteobacteria must import heme for their growth, since they
      cannot synthesize it. To import exogenous heme, Bartonella genomes encode for a
      complete heme uptake system enabling transportation of this compound into the
      cytoplasm and degrading it to release iron. In addition, these bacteria encode
      for four or five outer membrane heme binding proteins (Hbps). The structural
      genes of these highly homologous proteins are expressed differently depending on
      oxygen, temperature and heme concentrations. These proteins were hypothesized as
      being involved in various cellular processes according to their ability to bind
      heme and their regulation profile. In this report, we investigated the roles of
      the four Hbps of Bartonella henselae, responsible for cat scratch disease. We
      show that Hbps can bind heme in vitro. They are able to enhance the efficiency of
      heme uptake when co-expressed with a heme transporter in Escherichia coli. Using
      B. henselae Hbp knockdown mutants, we show that these proteins are involved in
      defense against the oxidative stress, colonization of human endothelial cell and
      survival in the flea.

PMID- 23144763
TI  - Diuretics prime plant immunity in Arabidopsis thaliana.
AB  - Plant activators are agrochemicals that activate the plant immune system, thereby
      enhancing disease resistance. Due to their prophylactic and durable effects on a
      wide spectrum of diseases, plant activators can provide synergistic crop
      protection when used in combination with traditional pest controls. Although
      plant activators have achieved great success in wet-rice farming practices in
      Asia, their use is still limited. To isolate novel plant activators applicable to
      other crops, we screened a chemical library using a method that can selectively
      identify immune-priming compounds. Here, we report the isolation and
      characterization of three diuretics, bumetanide, bendroflumethiazide and
      clopamide, as immune-priming compounds. These drugs upregulate the immunity
      related cell death of Arabidopsis suspension-cultured cells induced with an
      avirulent strain of Pseudomonas syringae pv. tomato in a concentration-dependent
      manner. The application of these compounds to Arabidopsis plants confers disease
      resistance to not only the avirulent but also a virulent strain of the pathogen.
      Unlike salicylic acid, an endogenous phytohormone that governs disease resistance
      in response to biotrophic pathogens, the three diuretic compounds analyzed here
      do not induce PR1 or inhibit plant growth, showing potential as lead compounds in
      a practical application.

PMID- 23144764
TI  - Urea amidolyase (DUR1,2) contributes to virulence and kidney pathogenesis of
      Candida albicans.
AB  - The intracellular enzyme urea amidolyase (Dur1,2p) enables C. albicans to utilize
      urea as a sole nitrogen source. Because deletion of the DUR1,2 gene reduces
      survival of C. albicans co-cultured with a murine macrophage cell line, we
      investigated the role of Dur1,2p in pathogenesis using a mouse model of
      disseminated candidiasis. A dur1,2Delta/dur1,2Delta strain was significantly less
      virulent than the wild-type strain, showing significantly higher survival rate,
      better renal function, and decreased and less sustained fungal colonization in
      kidney and brain. Complementation of the mutant restored virulence. DUR1,2
      deletion resulted in a milder host inflammatory reaction. Immunohistochemistry,
      flow cytometry, and magnetic resonance imaging showed decreased phagocytic
      infiltration into infected kidneys. Systemic cytokine levels of wild-type mice
      infected with the dur1,2 mutant showed a more balanced systemic pro-inflammatory
      cytokine response. Host gene expression and protein analysis in infected kidneys
      revealed parallel changes in the local immune response. Significant differences
      were observed in the kidney IL-1 inflammatory pathway, IL-15 signaling, MAP
      kinase signaling, and the alternative complement pathway. We conclude that
      Dur1,2p is important for kidney colonization during disseminated candidiasis and
      contributes to an unbalanced host inflammatory response and subsequent renal
      failure. Therefore, this Candida-specific enzyme may represent a useful drug
      target to protect the host from kidney damage associated with disseminated
      candidiasis.

PMID- 23144765
TI  - Calcitriol modulates the CD46 pathway in T cells.
AB  - The complement regulator CD46 is a costimulatory molecule for human T cells that
      induces a regulatory Tr1 phenotype, characterized by large amounts of IL-10
      secretion. Secretion of IL-10 upon CD46 costimulation is largely impaired in T
      cells from patients with multiple sclerosis (MS). Vitamin D can exert a direct
      effect on T cells, and may be beneficial in several pathologies, including MS. In
      this pilot study, we examined whether active vitamin D (1,25(OH)(2)D(3) or
      calcitriol) could modulate the CD46 pathway and restore IL-10 production by CD46
      costimulated CD4+ T cells from patients with MS. In healthy T cells, calcitriol
      profoundly affects the phenotype of CD46-costimulated CD4+ T cells, by increasing
      the expression of CD28, CD25, CTLA-4 and Foxp3 while it concomitantly decreased
      CD46 expression. Similar trends were observed in MS CD4+ T cells except for CD25
      for which a striking opposite effect was observed: while CD25 was normally
      induced on MS T cells by CD46 costimulation, addition of calcitriol consistently
      inhibited its induction. Despite the aberrant effect on CD25 expression,
      calcitriol increased the IL-10:IFNgamma ratio, characteristic of the CD46-induced
      Tr1 phenotype, in both T cells from healthy donors and patients with MS. Hence,
      we show that calcitriol affects the CD46 pathway, and that it promotes anti
      inflammatory responses mediated by CD46. Moreover, it might be beneficial for T
      cell responses in MS.

PMID- 23144766
TI  - Oral immunotherapy for pollen allergy using T-cell epitope-containing egg white
      derived from genetically manipulated chickens.
AB  - Peptide immunotherapy using T-cell epitopes is expected to be an effective
      treatment for allergic diseases such as Japanese cedar (Cryptomeria japonica; Cj)
      pollinosis. To develop a treatment for pollen allergy by inducing oral tolerance,
      we generated genetically manipulated (GM) chickens by retroviral gene
      transduction, to produce a fusion protein of chicken egg white lysozyme and a
      peptide derived from seven dominant human T-cell epitopes of Japanese cedar
      pollen allergens (cLys-7crp). The transgene sequence was detected in all chickens
      transduced with the retroviral vector. Transduction efficiency in blood cells
      correlated to transgene expression. Western blot analysis revealed that cLys-7crp
      was expressed in the egg white of GM hens. Mice induced to develop allergic
      rhinitis by Cj pollinosis were fed with cLys-7crp-containing egg white produced
      by GM chickens. Total and Cj allergen (Cry j 1)-specific IgE levels were
      significantly decreased in allergic mice fed with cLys-7crp-containing egg white
      compared with allergic mice fed with normal egg white. These results suggest that
      oral administration of T-cell epitope-containing egg white derived from GM
      chickens is effective for the induction of immune tolerance as an allergy
      therapy.

PMID- 23144767
TI  - Dynamic range of vertebrate retina ganglion cells: importance of active dendrites
      and coupling by electrical synapses.
AB  - The vertebrate retina has a very high dynamic range. This is due to the concerted
      action of its diverse cell types. Ganglion cells, which are the output cells of
      the retina, have to preserve this high dynamic range to convey it to higher brain
      areas. Experimental evidence shows that the firing response of ganglion cells is
      strongly correlated with their total dendritic area and only weakly correlated
      with their dendritic branching complexity. On the other hand, theoretical studies
      with simple neuron models claim that active and large dendritic trees enhance the
      dynamic range of single neurons. Theoretical models also claim that electrical
      coupling between ganglion cells via gap junctions enhances their collective
      dynamic range. In this work we use morphologically reconstructed multi
      compartmental ganglion cell models to perform two studies. In the first study we
      investigate the relationship between single ganglion cell dynamic range and
      number of dendritic branches/total dendritic area for both active and passive
      dendrites. Our results support the claim that large and active dendrites enhance
      the dynamic range of a single ganglion cell and show that total dendritic area
      has stronger correlation with dynamic range than with number of dendritic
      branches. In the second study we investigate the dynamic range of a square array
      of ganglion cells with passive or active dendritic trees coupled with each other
      via dendrodendritic gap junctions. Our results suggest that electrical coupling
      between active dendritic trees enhances the dynamic range of the ganglion cell
      array in comparison with both the uncoupled case and the coupled case with cells
      with passive dendrites. The results from our detailed computational modeling
      studies suggest that the key properties of the ganglion cells that endow them
      with a large dynamic range are large and active dendritic trees and electrical
      coupling via gap junctions.

PMID- 23144768
TI  - Performance of frontloading for smear microscopy in the diagnosis of pulmonary
      tuberculosis: a cross-sectional study at a referral hospital in Uganda.
AB  - OBJECTIVE: To compare the performance of frontloading and the standard WHO method
      for diagnosis of pulmonary TB at Mulago Hospital in order to validate the
      technique in this setting. METHODS: This was a cross-sectional study in which 229
      adult (>=18 years) TB suspects were consecutively enrolled. Suspects submitted
      three sputum samples as follows: at initial presentation, one hour after the
      first sample, and the next morning. The first and next morning samples formed the
      standard WHO method, while the first and the one hour later samples formed the
      frontloading method. Sample processing was by the standard N-acetyl L-cystein
      (NALC)-NaOH method, and fluorescent microscopy was done for both methods, while
      cultures of the first sample on Lowenstein-Jensen slants acted as a gold
      standard. The sensitivity, specificity and predictive values for the WHO standard
      and frontloading methods were compared. RESULTS: The sensitivity of both the
      frontloading and standard schemes was 91.1% while their specificities were 86.2%
      and 91.7% respectively. There was excellent agreement between the diagnostic
      capacity of the two methods (kappa statistic = 0.87, P<0.0001). The positive
      predictive value for the frontloading scheme was 87.2% and that for the standard
      approach was 91.9%, while the negative predictive values were 90.4% and 90.9%,
      respectively. Among the HIV positive patients, frontloading identified 59/79
      (74.7%) culture positive samples while the standard approach identified 55/79
      (69.6%). In the HIV sero-negative category, on the other hand, front-loading
      identified 48/110 (43.6%) culture positive samples compared to 45/110 (40.9%) by
      the standard approach. CONCLUSION: Frontloading based on smear examination of two
      same-day sputum samples has a similar performance to the current standard method
      and would not be associated with any significant missed diagnosis. It may
      therefore be advocated for use in our setting so as to reduce time to completion
      of diagnosis and patient loss to follow-up.

PMID- 23144771
TI  - Retraction: Late complications of clinical Clostridium histolyticum collagenase
      use in Dupuytren's disease.

PMID- 23144769
TI  - Quantitative comparison of the efficacy of various compounds in lowering
      intracellular cholesterol levels in Niemann-Pick type C fibroblasts.
AB  - Niemann-Pick Type C disease (NPC) is a lethal, autosomal recessive disorder
      caused by mutations in the NPC1 and NPC2 cholesterol transport proteins. NPC's
      hallmark symptoms include an accumulation of unesterified cholesterol and other
      lipids in the late endosomal and lysosomal cellular compartments, causing
      progressive neurodegeneration and death. Although the age of onset may vary in
      those affected, NPC most often manifests in juveniles, and is usually fatal
      before adolescence. In this study, we investigated the effects of various drugs,
      many of which modify the epigenetic control of NPC1/NPC2 gene expression, in
      lowering the otherwise harmful elevated intracellular cholesterol levels in NPC
      cells. Our studies utilized a previously described image analysis technique,
      which allowed us to make quantitative comparisons of the efficacy of these drugs
      in lowering cholesterol levels in a common NPC1 mutant model. Of the drugs
      analyzed, several that have been previously studied (vorinostat, panobinostat,
      and beta-cyclodextrin) significantly lowered the relative amount of unesterified
      cellular cholesterol, consistent with earlier observations. In addition, a novel
      potential treatment, rapamycin, likewise alleviated the NPC phenotype. We also
      studied combinations of effective compounds with beta-cyclodextrin; the addition
      of beta-cyclodextrin significantly enhanced the cholesterol-lowering activity of
      vorinostat and panobinostat, but had mixed effects with rapamycin. Collectively,
      these results may provide a basis for the eventual development of improved NPC
      therapies.

PMID- 23144770
TI  - Genome-wide association study heterogeneous cohort homogenization via subject
      weight knock-down.
AB  - Population structure can be a source of both false-positive and false-negative
      findings in a genome-wide association study. This article proposes an approach
      that helps to reduce the false-positives. It consists of homogenizing the
      diseased/healthy phenotype ratio across the cohort, by decreasing the statistical
      weight of selected individuals. After homogenization, the cohort is statistically
      handled as if originating from a single well-mixed population. The method was
      applied to homogenize a Parkinson's disease genome-wide association study cohort.

PMID- 23144773
TI  - The soluble guanylyl cyclase activator bay 58-2667 selectively limits
      cardiomyocyte hypertrophy.
AB  - BACKGROUND: Although evidence now suggests cGMP is a negative regulator of
      cardiac hypertrophy, the direct consequences of the soluble guanylyl cyclase
      (sGC) activator BAY 58-2667 on cardiac remodeling, independent of changes in
      hemodynamic load, has not been investigated. In the present study, we tested the
      hypothesis that the NO(*)-independent sGC activator BAY 58-2667 inhibits
      cardiomyocyte hypertrophy in vitro. Concomitant impact of BAY 58-2667 on cardiac
      fibroblast proliferation, and insights into potential mechanisms of action, were
      also sought. Results were compared to the sGC stimulator BAY 41-2272. METHODS:
      Neonatal rat cardiomyocytes were incubated with endothelin-1 (ET(1), 60nmol/L) in
      the presence and absence of BAY 41-2272 and BAY 58-2667 (0.01-0.3 umol/L).
      Hypertrophic responses and its triggers, as well as cGMP signaling, were
      determined. The impact of both sGC ligands on basal and stimulated cardiac
      fibroblast proliferation in vitro was also determined. RESULTS: We now
      demonstrate that BAY 58-2667 (0.01-0.3 umol/L) elicited concentration-dependent
      antihypertrophic actions, inhibiting ET(1)-mediated increases in cardiomyocyte 2D
      area and de novo protein synthesis, as well as suppressing ET(1)-induced
      cardiomyocyte superoxide generation. This was accompanied by potent increases in
      cardiomyocyte cGMP accumulation and activity of its downstream signal,
      vasodilator-stimulated phosphoprotein (VASP), without elevating cardiomyocyte
      cAMP. In contrast, submicromolar concentrations of BAY 58-2667 had no effect on
      basal or stimulated cardiac fibroblast proliferation. Indeed, only at
      concentrations >=10 umol/L was inhibition of cardiac fibrosis seen in vitro. The
      effects of BAY 58-2667 in both cell types were mimicked by BAY 41-2272.
      CONCLUSIONS: Our results demonstrate that BAY 58-2667 elicits protective,
      cardiomyocyte-selective effects in vitro. These actions are associated with sGC
      activation and are evident in the absence of confounding hemodynamic factors, at
      low (submicromolar) concentrations. Thus this distinctive sGC ligand may
      potentially represent an alternative therapeutic approach for limiting myocardial
      hypertrophy.

PMID- 23144772
TI  - Immune responses to ESAT-6 and CFP-10 by FASCIA and multiplex technology for
      diagnosis of M. tuberculosis infection; IP-10 is a promising marker.
AB  - BACKGROUND: There is a need for reliable markers to diagnose active and latent
      tuberculosis (TB). The interferon gamma release assays (IGRAs) are compared to
      the tuberculin skin test (TST) more specific, but cannot discriminate between
      recent or remote TB infection. Here the Flow-cytometric Assay for Specific Cell
      mediated Immune-response in Activated whole blood (FASCIA), which quantifies
      expanded T-lymphoblasts by flow-cytometric analysis after long-term antigen
      stimulation of whole blood, is combined with cytokine/chemokine analysis in the
      supernatant by multiplex technology for diagnosis of Mycobacterium tuberculosis
      (Mtb) infection. METHODS AND FINDINGS: Consecutive patients with suspected TB (n
      = 85), with microbiologically verified active pulmonary TB (n = 33), extra
      pulmonary TB (n = 21), clinical TB (n = 11), presumed latent TB infection (LTBI)
      (n = 23), patients negative for TB (n = 8) and 21 healthy controls were studied.
      Blood samples were analyzed with FASCIA and multiplex technology to determine and
      correlate proliferative responses and the value of 14 cytokines for diagnosis of
      Mtb infection: IFN- gamma, IL-2, TNF-alpha, IP-10, IL-12, IL-6, IL-4, IL-5, IL
      13, IL-17, MIP-1beta, GM-CSF, IFN-alpha2 and IL-10. Cytokine levels for IFN
      gamma, IP-10, MIP-1beta, IL-2, TNF-alpha, IL-6, IL-10, IL-13 and GM-CSF were
      significantly higher after stimulation with the Mtb specific antigens ESAT-6 and
      CFP-10 in patients with active TB compared to healthy controls (p<0.05) and
      correlated with proliferative responses. IP-10 was positive in all patients with
      verified TB, if using a combination of ESAT-6 and CFP-10 and was the only marker
      significantly more sensitive in detecting active TB then IFN-gamma (p = 0.012).
      Cytokine responses in patients with active TB were more frequent and detected at
      higher levels than in patients with LTBI. CONCLUSIONS: IP-10 seems to be an
      important marker for diagnosis of active and latent TB. Patients with active TB
      and LTBI responded with similar cytokine profiles against TB antigens but
      proliferative and cytokine responses were generally higher in patients with
      active TB.

PMID- 23144774
TI  - Fetal mesenchymal stromal cells differentiating towards chondrocytes acquire a
      gene expression profile resembling human growth plate cartilage.
AB  - We used human fetal bone marrow-derived mesenchymal stromal cells (hfMSCs)
      differentiating towards chondrocytes as an alternative model for the human growth
      plate (GP). Our aims were to study gene expression patterns associated with
      chondrogenic differentiation to assess whether chondrocytes derived from hfMSCs
      are a suitable model for studying the development and maturation of the GP.
      hfMSCs efficiently formed hyaline cartilage in a pellet culture in the presence
      of TGFbeta3 and BMP6. Microarray and principal component analysis were applied to
      study gene expression profiles during chondrogenic differentiation. A set of 232
      genes was found to correlate with in vitro cartilage formation. Several
      identified genes are known to be involved in cartilage formation and validate the
      robustness of the differentiating hfMSC model. KEGG pathway analysis using the
      232 genes revealed 9 significant signaling pathways correlated with cartilage
      formation. To determine the progression of growth plate cartilage formation, we
      compared the gene expression profile of differentiating hfMSCs with previously
      established expression profiles of epiphyseal GP cartilage. As differentiation
      towards chondrocytes proceeds, hfMSCs gradually obtain a gene expression profile
      resembling epiphyseal GP cartilage. We visualized the differences in gene
      expression profiles as protein interaction clusters and identified many protein
      clusters that are activated during the early chondrogenic differentiation of
      hfMSCs showing the potential of this system to study GP development.

PMID- 23144776
TI  - Spontaneous structural changes in actin regulate G-F transformation.
AB  - Transformations between G- (monomeric) and F-actin (polymeric) are important in
      cellular behaviors such as migration, cytokinesis, and morphing. In order to
      understand these transitions, we combined single-molecule Forster resonance
      energy transfer with total internal reflection fluorescence microscopy to examine
      conformational changes of individual actin protomers. We found that the protomers
      can take different conformational states and that the transition interval is in
      the range of hundreds of seconds. The distribution of these states was dependent
      on the environment, suggesting that actin undergoes spontaneous structural
      changes that accommodate itself to polymerization.

PMID- 23144775
TI  - Relevance of brain lesion location to cognition in relapsing multiple sclerosis.
AB  - OBJECTIVE: To assess the relationship between cognition and brain white matter
      (WM) lesion distribution and frequency in patients with relapsing-remitting
      multiple sclerosis (RR MS). METHODS: MRI-based T2 lesion probability map (LPM)
      was used to assess the relevance of brain lesion location for cognitive
      impairment in a group of 142 consecutive patients with RRMS. Significance of
      voxelwise analyses was p<0.05, cluster-corrected for multiple comparisons. The
      Rao Brief Repeatable Battery was administered at the time of brain MRI to
      categorize the MS population into cognitively preserved (CP) and cognitively
      impaired (CI). RESULTS: Out of 142 RRMS, 106 were classified as CP and 36 as CI.
      Although the CI group had greater WM lesion volume than the CP group (p = 0.001),
      T2 lesions tended to be less widespread across the WM. The peak of lesion
      frequency was almost twice higher in CI (61% in the forceps major) than in CP
      patients (37% in the posterior corona radiata). The voxelwise analysis confirmed
      that lesion frequency was higher in CI than in CP patients with significant
      bilateral clusters in the forceps major and in the splenium of the corpus
      callosum (p<0.05, corrected). Low scores of the Symbol Digit Modalities Test
      correlated with higher lesion frequency in these WM regions. CONCLUSIONS: Overall
      these results suggest that in MS patients, areas relevant for cognition lie
      mostly in the commissural fiber tracts. This supports the notion of a functional
      (multiple) disconnection between grey matter structures, secondary to damage
      located in specific WM areas, as one of the most important mechanisms leading to
      cognitive impairment in MS.

PMID- 23144777
TI  - Resolving the detailed structure of cortical and thalamic neurons in the adult
      rat brain with refined biotinylated dextran amine labeling.
AB  - Biotinylated dextran amine (BDA) has been used frequently for both anterograde
      and retrograde pathway tracing in the central nervous system. Typically, BDA
      labels axons and cell somas in sufficient detail to identify their topographical
      location accurately. However, BDA labeling often has proved to be inadequate to
      resolve the fine structural details of axon arbors or the dendrites of neurons at
      a distance from the site of BDA injection. To overcome this limitation, we varied
      several experimental parameters associated with the BDA labeling of neurons in
      the adult rat brain in order to improve the sensitivity of the method.
      Specifically, we compared the effect on labeling sensitivity of: (a) using 3,000
      or 10,000 MW BDA; (b) injecting different volumes of BDA; (c) co-injecting BDA
      with NMDA; and (d) employing various post-injection survival times. Following the
      extracellular injection of BDA into the visual cortex, labeled cells and axons
      were observed in both cortical and thalamic areas of all animals studied.
      However, the detailed morphology of axon arbors and distal dendrites was evident
      only under optimal conditions for BDA labeling that take into account the:
      molecular weight of the BDA used, concentration and volume of BDA injected, post
      injection survival time, and toning of the resolved BDA with gold and silver. In
      these instances, anterogradely labeled axons and retrogradely labeled dendrites
      were resolved in fine detail, approximating that which can be achieved with
      intracellularly injected compounds such as biocytin or fluorescent dyes.

PMID- 23144778
TI  - Identifying discrete states of a biological system using a novel step detection
      algorithm.
AB  - Identification of discrete states is a common task when studying biological
      systems on microscopic scales. Here, we present a novel step detection algorithm
      that is ideally suited to locate steplike features separating adjacent plateaus,
      even if they are smooth and hidden by noise. It can be adjusted to detect very
      low or narrow steps that cannot be recognized by conventional methods. We
      demonstrate the applicability of the technique on various experimental data and
      show strong evidence of sub-10-pN steps in atomic force spectroscopy measurements
      performed with living lymphocytes.

PMID- 23144779
TI  - Development of a non-invasive method, multiplex methylation specific PCR (MMSP),
      for early diagnosis of nasopharyngeal carcinoma.
AB  - Increasing evidence demonstrated that inactivation of tumor suppressor genes
      (TSGs) by aberrant promoter methylation is an early event during carcinogenesis.
      Aiming at developing early diagnostic or prognostic tools for various tumors, we
      took an EBV-associated tumor, nasopharyngeal carcinoma (NPC), as a model and
      developed a powerful assay based on "multiplex methylation specific-PCR (MMSP)".
      The MMSP assay was designed to detect tumor-specific methylation status of
      several NPC-related genes and was capable of acquiring multiplex information
      simultaneously through a single PCR reaction with the tiny tumor DNA derived from
      the direct body fluid close to the primary tumor. In this study, we collected
      paired nasopharyngeal (NP) swabs and NPC biopsies from 49 NPC patients and twenty
      noncancerous controls. A panel of markers including two EBV, and two cellular TSG
      markers were applied in this NPC-specific-MMSP assay. We optimized the working
      condition of MMSP so that it provides information equal to that from the
      corresponding separate PCRs. The results showed that MMSP patterns of NPC swab
      were largely consistent with those of corresponding biopsies and significantly
      distinguished themselves from those of 20 noncancerous volunteers. Among the 69
      samples (49 NPCs and 20 normal controls), the sensitivity of detecting NPC from
      NP swabs is 98%. The specificity is as high as 100%. In conclusion, being
      characterized by its noninvasiveness, high reproducibility and informativeness,
      MMSP assay is a reliable and potential diagnostic tool for NPC. It paves the way
      for the development of population screening and early diagnosis approaches for
      various tumor types.

PMID- 23144780
TI  - Deciphering the roles of BamB and its interaction with BamA in outer membrane
      biogenesis, T3SS expression and virulence in Salmonella.
AB  - The folding and insertion of beta-barrel proteins in the outer membrane of Gram
      negative bacteria is mediated by the BAM complex, which is composed of the outer
      membrane protein BamA and four lipoproteins BamB to BamE. In Escherichia coli
      and/or Salmonella, the BamB lipoprotein is involved in (i) beta-barrel protein
      assembly in the outer membrane, (ii) outer membrane permeability to antibiotics,
      (iii) the control of the expression of T3SS which are major virulence factors and
      (iv) the virulence of Salmonella. In E. coli, this protein has been shown to
      interact directly with BamA. In this study, we investigated the structure
      function relationship of BamB in order to assess whether the roles of BamB in
      these phenotypes were inter-related and whether they require the interaction of
      BamB with BamA. For this purpose, recombinant plasmids harbouring point mutations
      in bamB were introduced in a DeltaSalmonella bamB mutant. We demonstrated that
      the residues L173, L175 and R176 are crucial for all the roles of BamB and for
      the interaction of BamB with BamA. Moreover, the results obtained with a D229A
      BamB variant, which is unable to immunoprecipitate BamA, suggest that the
      interaction of BamB with BamA is not absolutely necessary for BamB function in
      outer-membrane protein assembly, T3SS expression and virulence. Finally, we
      showed that the virulence defect of the DeltabamB mutant is not related to its
      increased susceptibility to antimicrobials, as the D227A BamB variant fully
      restored the virulence of the mutant while having a similar antibiotic
      susceptibility to the DeltabamB strain. Overall, this study demonstrates that the
      different roles of BamB are not all inter-related and that L173, L175 and R176
      amino-acids are privileged sites for the design of BamB inhibitors that could be
      used as alternative therapeutics to antibiotics, at least against Salmonella.

PMID- 23144782
TI  - A measure of total research impact independent of time and discipline.
AB  - Authorship and citation practices evolve with time and differ by academic
      discipline. As such, indicators of research productivity based on citation
      records are naturally subject to historical and disciplinary effects. We observe
      these effects on a corpus of astronomer career data constructed from a database
      of refereed publications. We employ a simple mechanism to measure research output
      using author and reference counts available in bibliographic databases to develop
      a citation-based indicator of research productivity. The total research impact
      (tori) quantifies, for an individual, the total amount of scholarly work that
      others have devoted to his/her work, measured in the volume of research papers. A
      derived measure, the research impact quotient (riq), is an age-independent
      measure of an individual's research ability. We demonstrate that these measures
      are substantially less vulnerable to temporal debasement and cross-disciplinary
      bias than the most popular current measures. The proposed measures of research
      impact, tori and riq, have been implemented in the Smithsonian/NASA Astrophysics
      Data System.

PMID- 23144781
TI  - Symptoms and quality of life in late stage Parkinson syndromes: a longitudinal
      community study of predictive factors.
AB  - BACKGROUND: Palliative care is increasingly offered earlier in the cancer
      trajectory but rarely in Idiopathic Parkinson's Disease(IPD), Progressive
      Supranuclear Palsy(PSP) or Multiple System Atrophy(MSA). There is little
      longitudinal data of people with late stage disease to understand levels of need.
      We aimed to determine how symptoms and quality of life of these patients change
      over time; and what demographic and clinical factors predicted changes. METHODS:
      We recruited 82 patients into a longitudinal study, consenting patients with a
      diagnosis of IPD, MSA or PSP, stages 3-5 Hoehn and Yahr(H&Y). At baseline and
      then on up to 3 occasions over one year, we collected self-reported demographic,
      clinical, symptom, palliative and quality of life data, using Parkinson's
      specific and generic validated scales, including the Palliative care Outcome
      Scale (POS). We tested for predictors using multivariable analysis, adjusting for
      confounders. FINDINGS: Over two thirds of patients had severe disability, over
      one third being wheelchair-bound/bedridden. Symptoms were highly prevalent in all
      conditions - mean (SD) of 10.6(4.0) symptoms. More than 50% of the MSA and PSP
      patients died over the year. Over the year, half of the patients showed either an
      upward (worsening, 24/60) or fluctuant (8/60) trajectory for POS and symptoms.
      The strongest predictors of higher levels of symptoms at the end of follow-up
      were initial scores on POS (AOR 1.30; 95%CI:1.05-1.60) and being male (AOR 5.18;
      95% CI 1.17 to 22.92), both were more predictive than initial H&Y scores.
      INTERPRETATION: The findings point to profound and complex mix of non-motor and
      motor symptoms in patients with late stage IPD, MSA and PSP. Symptoms are not
      resolved and half of the patients deteriorate. Palliative problems are predictive
      of future symptoms, suggesting that an early palliative assessment might help
      screen for those in need of earlier intervention.

PMID- 23144783
TI  - Ranking transitive chemical-disease inferences using local network topology in
      the comparative toxicogenomics database.
AB  - Exposure to chemicals in the environment is believed to play a critical role in
      the etiology of many human diseases. To enhance understanding about environmental
      effects on human health, the Comparative Toxicogenomics Database (CTD;
      http://ctdbase.org) provides unique curated data that enable development of novel
      hypotheses about the relationships between chemicals and diseases. CTD
      biocurators read the literature and curate direct relationships between chemicals
      genes, genes-diseases, and chemicals-diseases. These direct relationships are
      then computationally integrated to create additional inferred relationships; for
      example, a direct chemical-gene statement can be combined with a direct gene
      disease statement to generate a chemical-disease inference (inferred via the
      shared gene). In CTD, the number of inferences has increased exponentially as the
      number of direct chemical, gene and disease interactions has grown. To help users
      navigate and prioritize these inferences for hypothesis development, we
      implemented a statistic to score and rank them based on the topology of the local
      network consisting of the chemical, disease and each of the genes used to make an
      inference. In this network, chemicals, diseases and genes are nodes connected by
      edges representing the curated interactions. Like other biological networks, node
      connectivity is an important consideration when evaluating the CTD network, as
      the connectivity of nodes follows the power-law distribution. Topological methods
      reduce the influence of highly connected nodes that are present in biological
      networks. We evaluated published methods that used local network topology to
      determine the reliability of protein-protein interactions derived from high
      throughput assays. We developed a new metric that combines and weights two of
      these methods and uniquely takes into account the number of common neighbors and
      the connectivity of each entity involved. We present several CTD inferences as
      case studies to demonstrate the value of this metric and the biological relevance
      of the inferences.

PMID- 23144784
TI  - Fishy aroma of social status: urinary chemo-signalling of territoriality in male
      fathead minnows (Pimephales promelas).
AB  - Chemical structures of several urinary reproductive pheromones in fish have been
      identified, and their role in the chemical communication of reproductive
      condition is well characterized. On the contrary, the role of chemical
      communication in signalling of social/territorial status in fish is poorly
      understood. Fathead minnows are an example of a fish species whose life history
      traits appear conducive to evolution of chemical communication systems that
      confer information about social/territorial status. Male reproduction in this
      species is dependent upon their ability to acquire and defend a high quality
      nesting territory, and to attract a female to the nest. We hypothesized that
      fathead minnow males use visual and urine-derived chemical cues to signal
      territorial status. To test this hypothesis, effects of territorial acquisition
      on male-specific secondary sex characteristics (SSCs) and urine volumes were
      first assessed. Second, frequencies of male urination in varying social contexts
      were examined. Finally, nuclear magnetic resonance-based metabolomics was used to
      identify urinary metabolites that were differentially excreted in the urine of
      territorial versus non-territorial males. The expression of SSCs, sperm, and
      urine volumes increased with territory acquisition, and either remained unchanged
      or decreased in non-territorial males. Frequency of male urination increased
      significantly in the presence of females (but not males), suggesting that females
      are the main target of the urinary signals. Territorial and non-territorial males
      had distinct urinary metabolomic profiles. An unforeseen finding was that one
      could discern future territorial status of males, based on their initial
      metabolomic profiles. Bile acids and volatile amines were identified as potential
      chemical signals of social status in the fathead minnow. The finding that
      trimethylamine (a fishy smelling volatile amine) may be a social cue is
      particularly interesting, because it is known to bind trace amine-associated
      receptors, indicating that these receptors may play role in chemical signalling
      of social status in fish.

PMID- 23144785
TI  - PICARA, an analytical pipeline providing probabilistic inference about a priori
      candidates genes underlying genome-wide association QTL in plants.
AB  - PICARA is an analytical pipeline designed to systematically summarize observed
      SNP/trait associations identified by genome wide association studies (GWAS) and
      to identify candidate genes involved in the regulation of complex trait
      variation. The pipeline provides probabilistic inference about a priori candidate
      genes using integrated information derived from genome-wide association signals,
      gene homology, and curated gene sets embedded in pathway descriptions. In this
      paper, we demonstrate the performance of PICARA using data for flowering time
      variation in maize - a key trait for geographical and seasonal adaption of
      plants. Among 406 curated flowering time-related genes from Arabidopsis, we
      identify 61 orthologs in maize that are significantly enriched for GWAS SNP
      signals, including key regulators such as FT (Flowering Locus T) and GI
      (GIGANTEA), and genes centered in the Arabidopsis circadian pathway, including
      TOC1 (Timing of CAB Expression 1) and LHY (Late Elongated Hypocotyl). In
      addition, we discover a regulatory feature that is characteristic of these a
      priori flowering time candidates in maize. This new probabilistic analytical
      pipeline helps researchers infer the functional significance of candidate genes
      associated with complex traits and helps guide future experiments by providing
      statistical support for gene candidates based on the integration of heterogeneous
      biological information.

PMID- 23144786
TI  - Spherical lenses and prisms lead to postural instability in both dyslexic and non
      dyslexic adolescents.
AB  - There is controversy as to whether dyslexic children present systematic postural
      deficiency. Clinicians use a combination of ophthalmic prisms and proprioceptive
      soles to improve postural performances. This study examines the effects of
      convergent prisms and spherical lenses on posture. Fourteen dyslexics (13-17
      years-old) and 11 non dyslexics (13-16 years-old) participated in the study.
      Quiet stance posturography was performed with the TechnoConcept device while
      subjects fixated a target at eye-level from a distance of 1_m. Four conditions
      were run: normal viewing; viewing the target with spherical lenses of -1 diopter
      (ACCOM1) over each eye; viewing with -3 diopters over each eye (ACCOM3); viewing
      with a convergent prism of 8 diopters per eye. Relative to normal viewing, the -1
      lenses increased the surface of body sway significantly whereas the -3 diopter
      lenses only resulted in a significant increase of antero-posterior body sway.
      Thus, adolescents would appear to cope more effectively with stronger conflicts
      rather than subtle ones. The prism condition resulted in a significant increase
      in both the surface and the antero-posterior body sway. Importantly, all of these
      effects were similar for the two groups. Wavelet analysis (time frequency domain)
      revealed high spectral power of antero-posterior sway for the prism condition in
      both groups. In the ACCOM3 condition, the spectral power of antero-posterior sway
      decreased for non dyslexics but increased for dyslexics suggesting that dyslexics
      encounter more difficulty with accommodation. The cancelling time for medium
      range frequency (believed to be controlled by the cerebellum), was shorter in
      dyslexics, suggesting fewer instances of optimal control. We conclude that
      dyslexics achieve similar postural performances albeit less efficiently. Prisms
      and lenses destabilize posture for all teenagers. Thus, contrary to adults,
      adolescents do not seem to use efferent, proprioceptive ocular motor signals to
      improve their posture, at least not immediately when confronted to convergence
      accommodation conflict.

PMID- 23144787
TI  - Oxytocin motivates non-cooperation in intergroup conflict to protect vulnerable
      in-group members.
AB  - Intergroup conflict is often driven by an individual's motivation to protect
      oneself and fellow group members against the threat of out-group aggression,
      including the tendency to pre-empt out-group threat through a competitive
      approach. Here we link such defense-motivated competition to oxytocin, a
      hypothalamic neuropeptide involved in reproduction and social bonding. An
      intergroup conflict game was developed to disentangle whether oxytocin motivates
      competitive approach to protect (i) immediate self-interest, (ii) vulnerable in
      group members, or (iii) both. Males self-administered oxytocin or placebo (double
      blind placebo-controlled) and made decisions with financial consequences to
      themselves, their fellow in-group members, and a competing out-group. Game
      payoffs were manipulated between-subjects so that non-cooperation by the out
      group had high vs. low impact on personal payoff (personal vulnerability), and
      high vs. low impact on payoff to fellow in-group members (in-group
      vulnerability). When personal vulnerability was high, non-cooperation was
      unaffected by treatment and in-group vulnerability. When personal vulnerability
      was low, however, in-group vulnerability motivated non-cooperation but only when
      males received oxytocin. Oxytocin fuels a defense-motivated competitive approach
      to protect vulnerable group members, even when personal fate is not at stake.

PMID- 23144788
TI  - The interplay of cis-regulatory elements rules circadian rhythms in mouse liver.
AB  - The mammalian circadian clock is driven by cell-autonomous transcriptional
      feedback loops that involve E-boxes, D-boxes, and ROR-elements. In peripheral
      organs, circadian rhythms are additionally affected by systemic factors. We show
      that intrinsic combinatorial gene regulation governs the liver clock. With a
      temporal resolution of 2 h, we measured the expression of 21 clock genes in mouse
      liver under constant darkness and equinoctial light-dark cycles. Based on these
      data and known transcription factor binding sites, we develop a six-variable gene
      regulatory network. The transcriptional feedback loops are represented by
      equations with time-delayed variables, which substantially simplifies modelling
      of intermediate protein dynamics. Our model accurately reproduces measured
      phases, amplitudes, and waveforms of clock genes. Analysis of the network reveals
      properties of the clock: overcritical delays generate oscillations; synergy of
      inhibition and activation enhances amplitudes; and combinatorial modulation of
      transcription controls the phases. The agreement of measurements and simulations
      suggests that the intrinsic gene regulatory network primarily determines the
      circadian clock in liver, whereas systemic cues such as light-dark cycles serve
      to fine-tune the rhythms.

PMID- 23144789
TI  - Stroke is predicted by low visuospatial in relation to other intellectual
      abilities and coronary heart disease by low general intelligence.
AB  - BACKGROUND: Low intellectual ability is associated with an increased risk of
      coronary heart disease and stroke. Most studies have used a general intelligence
      score. We studied whether three different subscores of intellectual ability
      predict these disorders. METHODS: We studied 2,786 men, born between 1934 and
      1944 in Helsinki, Finland, who as conscripts at age 20 underwent an intellectual
      ability test comprising verbal, visuospatial (analogous to Raven's progressive
      matrices) and arithmetic reasoning subtests. We ascertained the later occurrence
      of coronary heart disease and stroke from validated national hospital discharge
      and death registers. RESULTS: 281 men (10.1%) had experienced a coronary heart
      disease event and 131 (4.7%) a stroke event. Coronary heart disease was predicted
      by low scores in all subtests, hazard ratios for each standard deviation (SD)
      lower score ranging from 1.21 to 1.30 (confidence intervals 1.08 to 1.46). Stroke
      was predicted by a low visuospatial reasoning score, the corresponding hazard
      ratio being 1.23 (95% confidence interval 1.04 to 1.46), adjusted for year and
      age at testing. Adjusted in addition for the two other scores, the hazard ratio
      was 1.40 (1.10 to 1.79). This hazard ratio was little affected by adjustment for
      socioeconomic status in childhood and adult life, whereas the same adjustments
      attenuated the associations between intellectual ability and coronary heart
      disease. The associations with stroke were also unchanged when adjusted for
      systolic blood pressure at 20 years and reimbursement for adult antihypertensive
      medication. CONCLUSIONS: Stroke is predicted by low visuospatial reasoning scores
      in relation to scores in the two other subtests. This association may be mediated
      by common underlying causes such as impaired brain development, rather than by
      mechanisms associated with risk factors shared by stroke and coronary heart
      disease, such as socio-economic status, hypertension and atherosclerosis.

PMID- 23144790
TI  - The protease degrading sperm histones post-fertilization in sea urchin eggs is a
      nuclear cathepsin L that is further required for embryo development.
AB  - Proteolysis of sperm histones in the sea urchin male pronucleus is the
      consequence of the activation at fertilization of a maternal cysteine protease.
      We previously showed that this protein is required for male chromatin remodelling
      and for cell-cycle progression in the newly formed embryos. This enzyme is
      present in the nucleus of unfertilized eggs and is rapidly recruited to the male
      pronucleus after insemination. Interestingly, this cysteine-protease remains co
      localized with chromatin during S phase of the first cell cycle, migrates to the
      mitotic spindle in M-phase and is re-located to the nuclei of daughter cells
      after cytokinesis. Here we identified the protease encoding cDNA and found a high
      sequence identity to cathepsin proteases of various organisms. A phylogenetical
      analysis clearly demonstrates that this sperm histone protease (SpHp) belongs to
      the cathepsin L sub-type. After an initial phase of ubiquitous expression
      throughout cleavage stages, SpHp gene transcripts become restricted to
      endomesodermic territories during the blastula stage. The transcripts are
      localized in the invaginating endoderm during gastrulation and a gut specific
      pattern continues through the prism and early pluteus stages. In addition, a
      concomitant expression of SpHp transcripts is detected in cells of the
      skeletogenic lineage and in accordance a pharmacological disruption of SpHp
      activity prevents growth of skeletal rods. These results further document the
      role of this nuclear cathepsin L during development.

PMID- 23144791
TI  - Atrial tachyarrhythmia in Rgs5-null mice.
AB  - AIMS: The aim of this study was to elucidate the effects of regulator of G
      protein signaling 5 (Rgs5), a negative regulator of G protein-mediated signaling,
      on atrial repolarization and tachyarrhythmia (ATA) in mice. METHODS AND RESULTS:
      In present study, the incidence of ATA were increased in Rgs5(-/-) Langendorff
      perfused mouse hearts during program electrical stimulation (PES) (46.7%, 7 of
      15) and burst pacing (26.7%, 4 of 15) compared with wild-type (WT) mice (PES:
      7.1%,1 of 14; burst:7.1%,1 of 14) (P<0.05). And the duration of ATA also shown
      longer in Rgs5(-/-) heart than that in WT, 2 out of 15 hearts exhibited sustained
      ATA (>30 s) but none of them observed in WT mice. Atrial prolonged repolarization
      was observed in Rgs5(-/-) hearts including widened P wave in surface ECG
      recording, increased action potential duration (APD) and atrial effective
      refractory periods (AERP), all of them showed significant difference with WT mice
      (P<0.05). At the cellular level, whole-cell patch clamp recorded markedly
      decreased densities of repolarizing K(+) currents including I(Kur) (at +60 mV:
      14.0+/-2.2 pF/pA) and I(to) (at +60 mV: 16.7+/-1.3 pA/pF) in Rgs5(-/-) atrial
      cardiomyocytes, compared to those of WT mice (at +60 mV I(to): 20.4+/-2.0 pA/pF;
      I(kur): 17.9+/-2.0 pF/pA) (P<0.05). CONCLUSION: These results suggest that Rgs5
      is an important regulator of arrhythmogenesis in the mouse atrium and that the
      enhanced susceptibility to atrial tachyarrhythmias in Rgs5(-/-) mice may
      contribute to abnormalities of atrial repolarization.

PMID- 23144792
TI  - c-Fms signaling mediates neurofibromatosis Type-1 osteoclast gain-in-functions.
AB  - Skeletal abnormalities including osteoporosis and osteopenia occur frequently in
      both pediatric and adult neurofibromatosis type 1 (NF1) patients. NF1 (Nf1)
      haploinsufficient osteoclasts and osteoclast progenitors derived from both NF1
      patients and Nf1(+/-) mice exhibit increased differentiation, migration, and bone
      resorptive capacity in vitro, mediated by hyperactivation of p21(Ras) in response
      to limiting concentrations of macrophage-colony stimulating factor (M-CSF). Here,
      we show that M-CSF binding to its receptor, c-Fms, results in increased c-Fms
      activation in Nf1(+/) (-) osteoclast progenitors, mediating multiple gain-in
      functions through the downstream effectors Erk1/2 and p90RSK. PLX3397, a potent
      and selective c-Fms inhibitor, attenuated M-CSF mediated Nf1(+/-) osteoclast
      migration by 50%, adhesion by 70%, and pit formation by 60%. In vivo, we
      administered PLX3397 to Nf1(+/-) osteoporotic mice induced by ovariectomy (OVX)
      and evaluated changes in bone mass and skeletal architecture. We found that
      PLX3397 prevented bone loss in Nf1(+/-)-OVX mice by reducing osteoclast
      differentiation and bone resorptive activity in vivo. Collectively, these results
      implicate the M-CSF/c-Fms signaling axis as a critical pathway underlying the
      aberrant functioning of Nf1 haploinsufficient osteoclasts and may provide a
      potential therapeutic target for treating NF1 associated osteoporosis and
      osteopenia.

PMID- 23144794
TI  - Discrimination against rural-to-urban migrants: the role of the hukou system in
      China.
AB  - China's rural-urban dual society system is instituted by its unique hukou system.
      This system causes inequalities in social status between permanent urban and
      rural residents, and discrimination against rural-to-urban migrants is thus
      prevalent. A series of studies, based on system justification theory, sought to
      address the impact of the hukou system on the discrimination against rural-to
      urban migrants. Study 1 showed that the justification of the hukou system could
      predict discrimination operationalized using a social distance measure. Study 2
      found that priming of the proposed abolishment of the current hukou system led to
      reduced social distance. Study 3, using a recruiting scenario, further
      demonstrated that priming of the proposed abolishment of the system led to
      reduced discrimination in salary decision. Consistent with our predictions,
      discrimination against rural-to-urban migrants could be triggered by justifying
      the current hukou system, while priming of the abolishment of the system serves
      to decrease discrimination. The present research thereby sheds light on China's
      reform of its hukou system to achieve social justice and equality from a
      psychological perspective.

PMID- 23144793
TI  - Degeneration of axotomized projection neurons in the rat dLGN: temporal
      progression of events and their mitigation by a single administration of FGF2.
AB  - Removal of visual cortex in the rat axotomizes projection neurons in the dorsal
      lateral geniculate nucleus (dLGN), leading to cytological and structural changes
      and apoptosis. Biotinylated dextran amine was injected into the visual cortex to
      label dLGN projection neurons retrogradely prior to removing the cortex in order
      to quantify the changes in the dendritic morphology of these neurons that precede
      cell death. At 12 hours after axotomy we observed a loss of appendages and the
      formation of varicosities in the dendrites of projection neurons. During the next
      7 days, the total number of dendrites and the cross-sectional areas of the
      dendritic arbors of projection neurons declined to about 40% and 20% of normal,
      respectively. The response of dLGN projection neurons to axotomy was
      asynchronous, but the sequence of structural changes in individual neurons was
      similar; namely, disruption of dendrites began within hours followed by cell soma
      atrophy and nuclear condensation that commenced after the loss of secondary
      dendrites had occurred. However, a single administration of fibroblast growth
      factor-2 (FGF2), which mitigates injury-induced neuronal cell death in the dLGN
      when given at the time of axotomy, markedly reduced the dendritic degeneration of
      projection neurons. At 3 and 7 days after axotomy the number of surviving
      dendrites of dLGN projection neurons in FGF-2 treated rats was approximately 50%
      greater than in untreated rats, and the cross-sectional areas of dendritic arbors
      were approximately 60% and 50% larger. Caspase-3 activity in axotomized dLGN
      projection neurons was determined by immunostaining for fractin (fractin-IR), an
      actin cleavage product produced exclusively by activated caspase-3. Fractin-IR
      was seen in some dLGN projection neurons at 36 hours survival, and it increased
      slightly by 3 days. A marked increase in reactivity was seen by 7 days, with the
      entire dLGN filled with dense fractin-IR in neuronal cell somas and dendrites.

PMID- 23144795
TI  - Characterization of a distinct population of circulating human non-adherent
      endothelial forming cells and their recruitment via intercellular adhesion
      molecule-3.
AB  - Circulating vascular progenitor cells contribute to the pathological
      vasculogenesis of cancer whilst on the other hand offer much promise in
      therapeutic revascularization in post-occlusion intervention in cardiovascular
      disease. However, their characterization has been hampered by the many variables
      to produce them as well as their described phenotypic and functional
      heterogeneity. Herein we have isolated, enriched for and then characterized a
      human umbilical cord blood derived CD133(+) population of non-adherent
      endothelial forming cells (naEFCs) which expressed the hematopoietic progenitor
      cell markers (CD133, CD34, CD117, CD90 and CD38) together with mature endothelial
      cell markers (VEGFR2, CD144 and CD31). These cells also expressed low levels of
      CD45 but did not express the lymphoid markers (CD3, CD4, CD8) or myeloid markers
      (CD11b and CD14) which distinguishes them from 'early' endothelial progenitor
      cells (EPCs). Functional studies demonstrated that these naEFCs (i) bound Ulex
      europaeus lectin, (ii) demonstrated acetylated-low density lipoprotein uptake,
      (iii) increased vascular cell adhesion molecule (VCAM-1) surface expression in
      response to tumor necrosis factor and (iv) in co-culture with mature endothelial
      cells increased the number of tubes, tubule branching and loops in a 3
      dimensional in vitro matrix. More importantly, naEFCs placed in vivo generated
      new lumen containing vasculature lined by CD144 expressing human endothelial
      cells (ECs). Extensive genomic and proteomic analyses of the naEFCs showed that
      intercellular adhesion molecule (ICAM)-3 is expressed on their cell surface but
      not on mature endothelial cells. Furthermore, functional analysis demonstrated
      that ICAM-3 mediated the rolling and adhesive events of the naEFCs under shear
      stress. We suggest that the distinct population of naEFCs identified and
      characterized here represents a new valuable therapeutic target to control
      aberrant vasculogenesis.

PMID- 23144796
TI  - Mortality trends from 2003 to 2009 among adolescents and young adults in rural
      Western Kenya using a health and demographic surveillance system.
AB  - BACKGROUND: Targeted global efforts to improve survival of young adults need
      information on mortality trends; contributions from health and demographic
      surveillance system (HDSS) are required. METHODS AND FINDINGS: This study aimed
      to explore changing trends in deaths among adolescents (15-19 years) and young
      adults (20-24 years), using census and verbal autopsy data in rural western Kenya
      using a HDSS. Mid-year population estimates were used to generate all-cause
      mortality rates per 100,000 population by age and gender, by communicable (CD)
      and non-communicable disease (NCD) causes. Linear trends from 2003 to 2009 were
      examined. In 2003, all-cause mortality rates of adolescents and young adults were
      403 and 1,613 per 100,000 population, respectively, among females; and 217 and
      716 per 100,000, respectively, among males. CD mortality rates among females and
      males 15-24 years were 500 and 191 per 100,000 (relative risk [RR] 2.6; 95%
      confidence intervals [CI] 1.7-4.0; p<0.001). NCD mortality rates in same aged
      females and males were similar (141 and 128 per 100,000, respectively; p = 0.76).
      By 2009, young adult female all-cause mortality rates fell 53% (chi(2) for linear
      trend 30.4; p<0.001) and 61.5% among adolescent females (chi(2) for linear trend
      11.9; p<0.001). No significant CD mortality reductions occurred among males or
      for NCD mortality in either gender. By 2009, all-cause, CD, and NCD mortality
      rates were not significantly different between males and females, and among
      males, injuries equalled HIV as the top cause of death. CONCLUSIONS: This study
      found significant reductions in adolescent and young adult female mortality
      rates, evidencing the effects of targeted public health programmes, however, all
      cause and CD mortality rates among females remain alarmingly high. These data
      underscore the need to strengthen programmes and target strategies to reach both
      males and females, and to promote NCD as well as CD initiatives to reduce the
      mortality burden amongst both gender.

PMID- 23144797
TI  - Multi-purpose utility of circulating plasma DNA testing in patients with advanced
      cancers.
AB  - Tumor genomic instability and selective treatment pressures result in clonal
      disease evolution; molecular stratification for molecularly targeted drug
      administration requires repeated access to tumor DNA. We hypothesized that
      circulating plasma DNA (cpDNA) in advanced cancer patients is largely derived
      from tumor, has prognostic utility, and can be utilized for multiplex tumor
      mutation sequencing when repeat biopsy is not feasible. We utilized the Sequenom
      MassArray System and OncoCarta panel for somatic mutation profiling. Matched
      samples, acquired from the same patient but at different time points were
      evaluated; these comprised formalin-fixed paraffin-embedded (FFPE) archival tumor
      tissue (primary and/or metastatic) and cpDNA. The feasibility, sensitivity, and
      specificity of this high-throughput, multiplex mutation detection approach was
      tested utilizing specimens acquired from 105 patients with solid tumors referred
      for participation in Phase I trials of molecularly targeted drugs. The median
      cpDNA concentration was 17 ng/ml (range: 0.5-1600); this was 3-fold higher than
      in healthy volunteers. Moreover, higher cpDNA concentrations associated with
      worse overall survival; there was an overall survival (OS) hazard ratio of 2.4
      (95% CI 1.4, 4.2) for each 10-fold increase in cpDNA concentration and in
      multivariate analyses, cpDNA concentration, albumin, and performance status
      remained independent predictors of OS. These data suggest that plasma DNA in
      these cancer patients is largely derived from tumor. We also observed high
      detection concordance for critical 'hot-spot' mutations (KRAS, BRAF, PIK3CA) in
      matched cpDNA and archival tumor tissue, and important differences between
      archival tumor and cpDNA. This multiplex sequencing assay can be utilized to
      detect somatic mutations from plasma in advanced cancer patients, when safe
      repeat tumor biopsy is not feasible and genomic analysis of archival tumor is
      deemed insufficient. Overall, circulating nucleic acid biomarker studies have
      clinically important multi-purpose utility in advanced cancer patients and
      further studies to pursue their incorporation into the standard of care are
      warranted.

PMID- 23144798
TI  - O:2-CRM(197) conjugates against Salmonella Paratyphi A.
AB  - Enteric fevers remain a common and serious disease, affecting mainly children and
      adolescents in developing countries. Salmonella enterica serovar Typhi was
      believed to cause most enteric fever episodes, but several recent reports have
      shown an increasing incidence of S. Paratyphi A, encouraging the development of a
      bivalent vaccine to protect against both serovars, especially considering that at
      present there is no vaccine against S. Paratyphi A. The O-specific polysaccharide
      (O:2) of S. Paratyphi A is a protective antigen and clinical data have previously
      demonstrated the potential of using O:2 conjugate vaccines. Here we describe a
      new conjugation chemistry to link O:2 and the carrier protein CRM(197), using the
      terminus 3-deoxy-D-manno-octulosonic acid (KDO), thus leaving the O:2 chain
      unmodified. The new conjugates were tested in mice and compared with other O:2
      antigen conjugates, synthesized adopting previously described methods that use
      CRM(197) as carrier protein. The newly developed conjugation chemistry yielded
      immunogenic conjugates with strong serum bactericidal activity against S.
      Paratyphi A.

PMID- 23144799
TI  - Environmental and animal characteristics as factors associated with American
      cutaneous leishmaniasis in rural locations with presence of dogs, Brazil.
AB  - The aim of the study was to investigate the importance of dogs, other
      domesticated animals and environmental characteristics as risk factors in the
      epidemiology of American cutaneous leishmaniasis (ACL). A retrospective survey of
      cases of human ACL in the last ten years and visits to homes in rural locations
      were carried out in the municipality of Arapongas (southern Brazil) from 2008 to
      2010. ACL in humans was significantly associated with a distance of up to 25
      meters from the residence to a forest area (OR 5.08; 95% CI: 1.35-21.04),
      undergrowth area (OR 6.80; 95% CI: 1.69-45.33) and stream (OR 5.87; 95% CI: 1.15
      24.59); banana plants near the residence (OR 5.98; 95% CI: 1.49-39.84), absence
      of ceiling below the roof in the residence (OR 7.30; 95% CI: 1.26-158.1), the
      dumping of trash in the forest area (OR 26.33; 95% CI: 7.32-93.46) and presence
      of ACL in dogs in the surrounding area (OR 4.39; 95% CI: 1.37-13.45). In dogs,
      ACL was associated with a distance of 25 to 50 meters and 51 to 100 meters,
      respectively, from the residence to a forest area (OR 2.59; 95% CI: 1.08-5.98; OR
      3.29; 95% CI: 1.64-6.62), the presence of a stream up to 25 m from the residence
      (OR 6.23; 95% CI: 2.34-16.54) and banana plants near the residence (OR 0.45; 95%
      CI: 0.25-0.80). In the locations studied in the municipality of Arapongas
      (Brazil), the results reveal that canine infection increases the risk of human
      infection by ACL and the characteristics surrounding the residence increase the
      risk of infection in both humans and dogs. Thus, integrated environmental
      management could be a useful measure to avoid contact between humans and
      phlebotomines.

PMID- 23144801
TI  - The relative influences of phosphometabolites and pH on action potential
      morphology during myocardial reperfusion: a simulation study.
AB  - Myocardial ischemia-reperfusion (IR) injury represents a constellation of
      pathological processes that occur when ischemic myocardium experiences a
      restoration of perfusion. Reentrant arrhythmias, which represent a particularly
      lethal manifestation of IR injury, can result when ischemic tissue exhibits
      decreased excitability and/or changes of action potential duration (APD),
      conditions that precipitate unidirectional conduction block. Many of the cellular
      components that are involved with IR injury are modulated by pH and/or
      phosphometabolites such as ATP and phosphocreatine (PCr), all of which can be
      manipulated in vivo and potentially in the clinical setting. Using a mathematical
      model of the cardiomyocyte that we previously developed to study ischemia and
      reperfusion, we performed a series of simulations with the aim of determining
      whether pH- or phosphometabolite-related processes play a more significant role
      in generating changes in excitability and action potential morphology that are
      associated with the development of reentry. In our simulations, persistent
      shortening of APD, action potential amplitude (APA), and depolarization of the
      resting membrane potential were more severe when ATP and PCr availability were
      suppressed during reperfusion than when extracellular pH recovery was inhibited.
      Reduced phosphometabolite availability and pH recovery affected multiple ion
      channels and exchangers. Some of these effects were the result of direct
      modulation by phosphometabolites and/or acidosis, while others resulted from
      elevated sodium and calcium loads during reperfusion. In addition, increasing ATP
      and PCr availability during reperfusion was more beneficial in terms of
      increasing APD and APA than was increasing the amount of pH recovery. Together,
      these results suggest that therapies directed at increasing ATP and/or PCr
      availability during reperfusion may be more beneficial than perturbing pH
      recovery with regard to mitigating action potential changes that increase the
      likelihood of reentrant arrhythmias.

PMID- 23144800
TI  - Spermine attenuates the action of the DNA intercalator, actinomycin D, on DNA
      binding and the inhibition of transcription and DNA replication.
AB  - The anticancer activity of DNA intercalators is related to their ability to
      intercalate into the DNA duplex with high affinity, thereby interfering with DNA
      replication and transcription. Polyamines (spermine in particular) are almost
      exclusively bound to nucleic acids and are involved in many cellular processes
      that require nucleic acids. Until now, the effects of polyamines on DNA
      intercalator activities have remained unclear because intercalation is the most
      important mechanism employed by DNA-binding drugs. Herein, using actinomycin D
      (ACTD) as a model, we have attempted to elucidate the effects of spermine on the
      action of ACTD, including its DNA-binding ability, RNA and DNA polymerase
      interference, and its role in the transcription and replication inhibition of
      ACTD within cells. We found that spermine interfered with the binding and
      stabilization of ACTD to DNA. The presence of increasing concentrations of
      spermine enhanced the transcriptional and replication activities of RNA and DNA
      polymerases, respectively, in vitro treated with ActD. Moreover, a decrease in
      intracellular polyamine concentrations stimulated by methylglyoxal
      bis(guanylhydrazone) (MGBG) enhanced the ACTD-induced inhibition of c-myc
      transcription and DNA replication in several cancer cell lines. The results
      indicated that spermine attenuates ACTD binding to DNA and its inhibition of
      transcription and DNA replication both in vitro and within cells. Finally, a
      synergistic antiproliferative effect of MGBG and ACTD was observed in a cell
      viability assay. Our findings will be of significant relevance to future
      developments in combination with cancer therapy by enhancing the anticancer
      activity of DNA interactors through polyamine depletion.

PMID- 23144802
TI  - Screening for and verification of novel mutations associated with drug resistance
      in the HIV type 1 subtype B(') in China.
AB  - OBJECTIVE: Mutations associated with HIV drug resistance have been extensively
      characterized at the HIV-1 polymerase domain, but more studies have verified that
      mutations outside of the polymerase domain also results in resistance to
      antiviral drugs. In this study, mutations were identified in 354 patients
      experiencing antiretroviral therapy (ART) failure and in 97 naive-therapy
      patients. Mutations whose impact on antiviral drugs was unknown were verified by
      phenotypic testing. METHODS: Pol sequences of HIV subtype B(') obtained from
      patients experiencing ART failure and from naive-therapy patients were analyzed
      for mutations distinct between two groups. Mutations that occurred at a
      significantly higher frequency in the ART failure than the naive-therapy group
      were submitted to the Stanford HIV Drug Resistance Database (SHDB) to analyze the
      correlation between HIV mutations and drug resistance. For mutations whose impact
      on the antiviral drug response is unknown, the site-directed mutagenesis approach
      was applied to construct plasmids containing the screened mutations. 50%
      inhibitory concentration (IC(50)) to AZT, EFV and NVP was measured to determine
      the response of the genetically constructed viruses to antiviral drugs. RESULTS:
      7 mutations at 6 positions of the RT region, D123E, V292I, K366R, T369A, T369V,
      A371V and I375V, occurred more frequently in the ART failure group than the naive
      therapy group. Phenotypic characterization of these HIV mutants revealed that
      constructed viruses with mutations A371V and T369V exhibited dual resistance to
      AZT and EFV respectively, whereas the other 5 mutations showed weak resistance.
      Although the impact of the other six mutations on response to NVP was minimal,
      mutation T369V could enhance resistance to NVP. CONCLUSIONS: This study
      demonstrated that mutations at the RT C-terminal in subtype B' could result in
      resistance to RT inhibitors if the mutations occurred alone, but that some
      mutations could promote susceptibility to antiviral drugs.

PMID- 23144803
TI  - Identification and cluster analysis of Streptococcus pyogenes by MALDI-TOF mass
      spectrometry.
AB  - BACKGROUND: Whole-cell matrix-assisted laser desorption ionization time-of-flight
      (MALDI-TOF) mass spectrometry (MS) has been successfully applied for bacterial
      identification and typing of many pathogens. The fast and reliable qualities of
      MALDI-TOF MS make it suitable for clinical diagnostics. MALDI-TOF MS for the
      identification and cluster analysis of Streptococcus pyogenes, however, has not
      been reported. The goal of our study was to evaluate this approach for the rapid
      identification and typing of S. pyogenes. METHODS: 65 S. pyogenes isolates were
      obtained from the hospital. The samples were prepared and MALDI-TOF MS
      measurements were conducted as previously reported. Identification of unknown
      spectra was performed via a pattern recognition algorithm with a reference
      spectra and a dendrogram was constructed using the statistical toolbox in Matlab
      7.1 integrated in the MALDI Biotyper 2.0 software. RESULTS: For identification,
      61 of 65 S. pyogenes isolates could be identified correctly by MALDI-TOF MS with
      BioType 2.0 when compared to biochemical identification (API Strep), with an
      accuracy of 93.85%. In clustering analysis, 44 of 65 isolates were in accordance
      with those established by M typing, with a matching rate of 67.69%. When only the
      M type prevalence in China was considered, 41 of 45 isolates were in agreement
      with M typing, with a matching rate of 91.1%. CONCLUSIONS: It was here shown that
      MALDI-TOF MS with Soft Biotype 2.0 and its database could facilitate rapid
      identification of S. pyogenes. It may present an attractive alternative to
      traditional biochemical methods of identification. However, for classification,
      more isolates and advances in the MALDI-TOF MS technology are needed to improve
      accuracy.

PMID- 23144804
TI  - Scribble acts in the Drosophila fat-hippo pathway to regulate warts activity.
AB  - Epithelial cells are the major cell-type for all organs in multicellular
      organisms. In order to achieve correct organ size, epithelial tissues need
      mechanisms that limit their proliferation, and protect tissues from damage caused
      by defective epithelial cells. Recently, the Hippo signaling pathway has emerged
      as a major mechanism that orchestrates epithelial development. Hippo signaling is
      required for cells to stop proliferation as in the absence of Hippo signaling
      tissues continue to proliferate and produce overgrown organs or tumors. Studies
      in Drosophila have led the way in providing a framework for how Hippo alters the
      pattern of gene transcription in target cells, leading to changes in cell
      proliferation, survival, and other behaviors. Scribble (Scrib) belongs to a class
      of neoplastic tumor suppressor genes that are required to establish apical-basal
      cell polarity. The disruption of apical-basal polarity leads to uncontrolled cell
      proliferation of epithelial cells. The interaction of apical basal polarity genes
      with the Hippo pathway has been an area of intense investigation. Loss of scrib
      has been known to affect Hippo pathway targets, however, its functions in the
      Hippo pathway still remain largely unknown. We investigated the interactions of
      Scrib with the Hippo pathway. We present data suggesting that Drosophila scrib
      acts downstream of the Fat (Ft) receptor, and requires Hippo signaling for its
      growth regulatory functions. We show that Ft requires Scrib to interact with
      Expanded (Ex) and Dachs (D), and for regulating Warts (Wts) levels and stability,
      thus placing Scrib in the Hippo pathway network.

PMID- 23144806
TI  - Paradoxical impact of two folate receptors, FRalpha and RFC, in ovarian cancer:
      effect on cell proliferation, invasion and clinical outcome.
AB  - Despite being an essential vitamin, folate has been implicated to enhance tumor
      growth, as evidenced by reports on overexpression of folate receptor alpha
      (FRalpha) in carcinomas. The role of another folate transporter, reduced folate
      carrier (RFC), is largely unknown. This study investigated the roles of folate,
      FRalpha and RFC in ovarian cancers. We demonstrated FRalpha mRNA and protein
      overexpression and reduced RFC expression in association with FRalpha gene
      amplification and RFC promoter hypermethylation, respectively. FRalpha
      overexpression was associated with tumor progression while RFC expression
      incurred a favorable clinical outcome. Such reciprocal expression pattern was
      also observed in ovarian cancer cell lines. Folate was shown to promote cancer
      cell proliferation, migration and invasion in vitro, and down-regulate E-cadherin
      expression. This effect was blocked after either stable knockdown of FRalpha or
      ectopic overexpression of RFC. This hitherto unreported phenomenon suggests that,
      RFC can serve as a balancing partner of FRalpha and confer a protective effect in
      patients with high FRalpha-expressing ovarian carcinomas, as evidenced by their
      prolonged overall and disease-free survivals. In conclusion, we report on the
      paradoxical impact of FRalpha (putative oncogenic) and RFC (putative tumor
      suppressive) in human malignancies. FRalpha and RFC may potentially be explored
      as therapeutic target or prognostic marker respectively. We recommend caution and
      additional research on folate supplements in cancer patients.

PMID- 23144805
TI  - Modification of heterotrimeric G-proteins in Swiss 3T3 cells stimulated with
      Pasteurella multocida toxin.
AB  - Many bacterial toxins covalently modify components of eukaryotic signalling
      pathways in a highly specific manner, and can be used as powerful tools to
      decipher the function of their molecular target(s). The Pasteurella multocida
      toxin (PMT) mediates its cellular effects through the activation of members of
      three of the four heterotrimeric G-protein families, G(q), G(12) and G(i). PMT
      has been shown by others to lead to the deamidation of recombinant Galpha(i) at
      Gln-205 to inhibit its intrinsic GTPase activity. We have investigated
      modification of native Galpha subunits mediated by PMT in Swiss 3T3 cells using 2
      D gel electrophoresis and antibody detection. An acidic change in the isoelectric
      point was observed for the Galpha subunit of the G(q) and G(i) families following
      PMT treatment of Swiss 3T3 cells, which is consistent with the deamidation of
      these Galpha subunits. Surprisingly, PMT also induced a similar modification of
      Galpha(11), a member of the G(q) family of G-proteins that is not activated by
      PMT. Furthermore, an alkaline change in the isoelectric point of Galpha(13) was
      observed following PMT treatment of cells, suggesting differential modification
      of this Galpha subunit by PMT. G(s) was not affected by PMT treatment. Prolonged
      treatment with PMT led to a reduction in membrane-associated Galpha(i), but not
      Galpha(q). We also show that PMT inhibits the GTPase activity of G(q).

PMID- 23144809
TI  - Design principles of a genetic alarm clock.
AB  - Turning genes on and off is a mechanism by which cells and tissues make
      phenotypic decisions. Gene network motifs capable of supporting two or more
      steady states and thereby providing cells with a plurality of possible phenotypes
      are referred to as genetic switches. Modeled on the bases of naturally occurring
      genetic networks, synthetic biologists have successfully constructed artificial
      switches, thus opening a door to new possibilities for improvement of the known,
      but also the design of new synthetic genetic circuits. One of many obstacles to
      overcome in such efforts is to understand and hence control intrinsic noise which
      is inherent in all biological systems. For some motifs the noise is negligible;
      for others, fluctuations in the particle number can be comparable to its average.
      Due to their slowed dynamics, motifs with positive autoregulation tend to be
      highly sensitive to fluctuations of their chemical environment and are in general
      very noisy, especially during transition (switching). In this article we use
      stochastic simulations (Gillespie algorithm) to model such a system, in
      particular a simple bistable motif consisting of a single gene with positive
      autoregulation. Due to cooperativety, the dynamical behavior of this kind of
      motif is reminiscent of an alarm clock - the gene is (nearly) silent for some
      time after it is turned on and becomes active very suddenly. We investigate how
      these sudden transitions are affected by noise and show that under certain
      conditions accurate timing can be achieved. We also examine how promoter
      complexity influences the accuracy of this timing mechanism.

PMID- 23144807
TI  - Monoaminergic modulation of spinal viscero-sympathetic function in the neonatal
      mouse thoracic spinal cord.
AB  - Descending serotonergic, noradrenergic, and dopaminergic systems project
      diffusely to sensory, motor and autonomic spinal cord regions. Using neonatal
      mice, this study examined monoaminergic modulation of visceral sensory input and
      sympathetic preganglionic output. Whole-cell recordings from sympathetic
      preganglionic neurons (SPNs) in spinal cord slice demonstrated that serotonin,
      noradrenaline, and dopamine modulated SPN excitability. Serotonin depolarized
      all, while noradrenaline and dopamine depolarized most SPNs. Serotonin and
      noradrenaline also increased SPN current-evoked firing frequency, while both
      increases and decreases were seen with dopamine. In an in vitro thoracolumbar
      spinal cord/sympathetic chain preparation, stimulation of splanchnic nerve
      visceral afferents evoked reflexes and subthreshold population synaptic
      potentials in thoracic ventral roots that were dose-dependently depressed by the
      monoamines. Visceral afferent stimulation also evoked bicuculline-sensitive
      dorsal root potentials thought to reflect presynaptic inhibition via primary
      afferent depolarization. These dorsal root potentials were likewise dose
      dependently depressed by the monoamines. Concomitant monoaminergic depression of
      population afferent synaptic transmission recorded as dorsal horn field
      potentials was also seen. Collectively, serotonin, norepinephrine and dopamine
      were shown to exert broad and comparable modulatory regulation of viscero
      sympathetic function. The general facilitation of SPN efferent excitability with
      simultaneous depression of visceral afferent-evoked motor output suggests that
      descending monoaminergic systems reconfigure spinal cord autonomic function away
      from visceral sensory influence. Coincident monoaminergic reductions in dorsal
      horn responses support a multifaceted modulatory shift in the encoding of spinal
      visceral afferent activity. Similar monoamine-induced changes have been observed
      for somatic sensorimotor function, suggesting an integrative modulatory response
      on spinal autonomic and somatic function.

PMID- 23144808
TI  - Activation of haem-oxidized soluble guanylyl cyclase with BAY 60-2770 in human
      platelets lead to overstimulation of the cyclic GMP signaling pathway.
AB  - BACKGROUND AND AIMS: Nitric oxide-independent soluble guanylyl cyclase (sGC)
      activators reactivate the haem-oxidized enzyme in vascular diseases. This study
      was undertaken to investigate the anti-platelet mechanisms of the haem
      independent sGC activator BAY 60-2770 in human washed platelets. The hypothesis
      that sGC oxidation potentiates the anti-platelet activities of BAY 60-2770 has
      been tested. METHODS: Human washed platelet aggregation and adhesion assays, as
      well as flow cytometry for alpha(IIb)beta(3) integrin activation and Western blot
      for alpha1 and beta1 sGC subunits were performed. Intracellular calcium levels
      were monitored in platelets loaded with a fluorogenic calcium-binding dye
      (FluoForte). RESULTS: BAY 60-2770 (0.001-10 uM) produced significant inhibition
      of collagen (2 ug/ml)- and thrombin (0.1 U/ml)-induced platelet aggregation that
      was markedly potentiated by the sGC inhibitor ODQ (10 uM). In fibrinogen-coated
      plates, BAY 60-2770 significantly inhibited platelet adhesion, an effect
      potentiated by ODQ. BAY 60-2770 increased the cGMP levels and reduced the
      intracellular Ca(2+) levels, both of which were potentiated by ODQ. The cell
      permeable cGMP analogue 8-Br-cGMP (100 uM) inhibited platelet aggregation and
      Ca(2+) levels in an ODQ-insensitive manner. The cAMP levels remained unchanged by
      BAY 60-2770. Collagen- and thrombin-induced alpha(IIb)beta(3) activation was
      markedly inhibited by BAY 60-2770 that was further inhibited by ODQ. The effects
      of sodium nitroprusside (3 uM) were all prevented by ODQ. Incubation with ODQ (10
      uM) significantly reduced the protein levels of alpha1 and beta1 sGC subunits,
      which were prevented by BAY 60-2770. CONCLUSION: The inhibitory effects of BAY 60
      2770 on aggregation, adhesion, intracellular Ca(2+) levels and alpha(IIb)beta(3)
      activation are all potentiated in haem-oxidizing conditions. BAY 60-2770 prevents
      ODQ-induced decrease in sGC protein levels. BAY 60-2770 could be of therapeutic
      interest in cardiovascular diseases associated with thrombotic complications.

PMID- 23144811
TI  - Intracranial ependymoma: long-term results in a series of 21 patients treated
      with stereotactic (125)iodine brachytherapy.
AB  - BACKGROUND: We evaluated the long-term outcome in patients harboring intracranial
      ependymomas treated with interstitial brachytherapy (IBT). METHODS: Twenty-one
      patients (M/F = 9/12; median age: 29 years; range: 8-70 years), diagnosed with
      intracranial ependymoma (1 WHO I, 11 WHO II, 9 WHO III) were treated with IBT
      using stereotactically implanted (125)Iodine seeds between 1987 and 2010, either
      primarily, as adjuvant therapy following incomplete resection, or as salvage
      treatment upon tumor recurrence. Sixteen of 21 patients underwent microsurgical
      resection prior to IBT; in 5 patients, IBT was performed primarily after
      stereotactic biopsy for histological diagnosis. The cumulative tumor surface dose
      ranged from 50-65 Gy treating a median tumor volume of 3.6 ml (range, 0.3-11.6
      ml). A median follow-up period of 105.3 months (range, 12.7-286.2 months) was
      evaluated. RESULTS: Actuarial 2-, 5- and 10-years overall- and disease-specific
      survival rates after IBT were each 90% and 100% at all times for ependymomas WHO
      I/II, for anaplastic ependymomas WHO III 100%, 100%, 70% and 100%, 100%, 86%,
      respectively. The neurological status of seven patients improved, while there was
      no change in 12 and deterioration in 2 patients, respectively. Follow-up MR
      images disclosed a complete tumor remission in 3, a partial remission in 12 and a
      stable disease in 6 patients. Treatment-associated morbidity only occurred in a
      single patient. CONCLUSIONS: This study shows that stereotactic IBT for
      intracranial ependymomas is safe and can provide a high degree of local tumor
      control. Due to the low rate of side effects, IBT may evolve into an attractive
      alternative to microsurgery in ependymomas located in eloquent areas or as a
      salvage treatment.

PMID- 23144810
TI  - High prevalence of vitamin D insufficiency in China: relationship with the levels
      of parathyroid hormone and markers of bone turnover.
AB  - There is a lack of large-scale studies on vitamin D status and its relationship
      to parathyroid hormone (PTH) and bone turnover markers in adults living in
      Shanghai. The objectives were to determine the prevalence of vitamin D
      insufficiency in Shanghai and to investigate the relationship of 25(OH)D with
      parathyroid function and bone turnover markers. This cross-sectional study
      involved 649 men and 1939 women aged 20-89 years who were randomly sampled in
      Shanghai. Serum concentrations of 25(OH)D, PTH, albumin, and bone turnover
      markers were measured. During the winter season, the prevalence of vitamin D
      insufficiency (<30 ng/mL) was 84% in males and 89% in females. The prevalence of
      vitamin D deficiency (<20 ng/mL) was 30% in males and 46% in females. With
      increasing serum 25(OH)D concentrations categorized as <10, 10-20, 20-30, and
      >=30 ng/mL, the mean PTH and bone turnover markers levels gradually decreasd in
      both sexes (p<0.001). There was an inverse relationship between the serum 25(OH)D
      and PTH concentrations in both genders, but no threshold of 25(OH)D at which PTH
      levels plateaued was observed. There were modest but significantly inverse
      relationships between the levels of 25(OH)D and bone turnover markers, but no
      plateau was observed for serum 25(OH)D levels up to 40 ng/mL.

PMID- 23144812
TI  - LBoost: A boosting algorithm with application for epistasis discovery.
AB  - Many human diseases are attributable to complex interactions among genetic and
      environmental factors. Statistical tools capable of modeling such complex
      interactions are necessary to improve identification of genetic factors that
      increase a patient's risk of disease. Logic Forest (LF), a bagging ensemble
      algorithm based on logic regression (LR), is able to discover interactions among
      binary variables predictive of response such as the biologic interactions that
      predispose individuals to disease. However, LF's ability to recover interactions
      degrades for more infrequently occurring interactions. A rare genetic interaction
      may occur if, for example, the interaction increases disease risk in a patient
      subpopulation that represents only a small proportion of the overall patient
      population. We present an alternative ensemble adaptation of LR based on boosting
      rather than bagging called LBoost. We compare the ability of LBoost and LF to
      identify variable interactions in simulation studies. Results indicate that
      LBoost is superior to LF for identifying genetic interactions associated with
      disease that are infrequent in the population. We apply LBoost to a subset of
      single nucleotide polymorphisms on the PRDX genes from the Cancer Genetic Markers
      of Susceptibility Breast Cancer Scan to investigate genetic risk for breast
      cancer. LBoost is publicly available on CRAN as part of the LogicForest package,
      http://cran.r-project.org/.

PMID- 23144813
TI  - Hematopoietic stem/progenitor cell proliferation and differentiation is
      differentially regulated by high-density and low-density lipoproteins in mice.
AB  - RATIONALE: Hematopoietic stem/progenitor cells (HSPC) are responsible for
      maintaining the blood system as a result of their self-renewal and multilineage
      differentiation capacity. Recently, studies have suggested that HDL cholesterol
      may inhibit and impaired cholesterol efflux may increase HSPC proliferation and
      differentiation. OBJECTIVES: We hypothesized that LDL may enhance HSPC
      proliferation and differentiation while HDL might have the opposing effect which
      might influence the size of the pool of inflammatory cells. METHODS AND RESULTS:
      HSPC number and function were studied in hypercholesterolemic LDL receptor
      knockout (LDLr(-/-)) mice on high fat diet. Hypercholesterolemia was associated
      with increased frequency of HSPC, monocytes and granulocytes in the peripheral
      blood (PB). In addition, an increased proportion of BM HSPC was in G(2)M of the
      cell cycle, and the percentage of HSPC and granulocyte-macrophage progenitors
      (GMP) increased in BM of LDLr(-/-) mice. When BM Lin-Sca-1+cKit+ (i.e. "LSK")
      cells were cultured in the presence of LDL in vitro we also found enhanced
      differentiation towards monocytes and granulocytes. Furthermore, LDL promoted
      lineage negative (Lin-) cells motility. The modulation by LDL on HSPC
      differentiation into granulocytes and motility was inhibited by inhibiting ERK
      phosphorylation. By contrast, when mice were infused with human apoA-I (the major
      apolipoprotein of HDL) or reconstituted HDL (rHDL), the frequency and
      proliferation of HSPC was reduced in BM in vivo. HDL also reversed the LDL
      induced monocyte and granulocyte differentiation in vitro. CONCLUSION: Our data
      suggest that LDL and HDL have opposing effects on HSPC proliferation and
      differentiation. It will be of interest to determine if breakdown of HSPC
      homeostasis by hypercholesterolemia contributes to inflammation and
      atherosclerosis progression.

PMID- 23144814
TI  - Does seeing ice really feel cold? Visual-thermal interaction under an illusory
      body-ownership.
AB  - Although visual information seems to affect thermal perception (e.g. red color is
      associated with heat), previous studies have failed to demonstrate the
      interaction between visual and thermal senses. However, it has been reported that
      humans feel an illusory thermal sensation in conjunction with an apparently
      thermal visual stimulus placed on a prosthetic hand in the rubber hand illusion
      (RHI) wherein an individual feels that a prosthetic (rubber) hand belongs to
      him/her. This study tests the possibility that the ownership of the body surface
      on which a visual stimulus is placed enhances the likelihood of a visual-thermal
      interaction. We orthogonally manipulated three variables: induced hand-ownership,
      visually-presented thermal information, and tactically-presented physical thermal
      information. Results indicated that the sight of an apparently-thermal object on
      a rubber hand that is illusorily perceived as one's own hand affects thermal
      judgments about the object physically touching this hand. This effect was not
      observed without the RHI. The importance of ownership of a body part that is
      touched by the visual object on the visual-thermal interaction is discussed.

PMID- 23144815
TI  - Identification of an abbreviated test battery for detection of HIV-associated
      neurocognitive impairment in an early-managed HIV-infected cohort.
AB  - BACKGROUND: HIV-associated neurocognitive disorders (HAND) remain prevalent
      despite improved antiretroviral treatment (ART), and it is essential to have a
      sensitive and specific HAND screening tool. METHODS: Participants were 200 HIV
      infected US military beneficiaries, managed early in the course of HIV infection,
      had few comorbidities, and had open access to ART. Participants completed a
      comprehensive, seven-domain (16-test), neuropsychological battery (~120 min);
      neurocognitive impairment (NCI) was determined using a standardized score derived
      from demographically adjusted T-scores (global deficit score >=0.5). Restricting
      the estimated administration time of the screening battery to < = 20 minutes, we
      examined the sensitivity and specificity of detecting NCI for all possible
      combinations of 2-, 3-, and 4- tests from the comprehensive battery. RESULTS:
      Participants were relatively healthy (median CD4 count: 546 cells/mm(3)) with 64%
      receiving ART. Prevalence of NCI was low (19%). The best 2-test screener included
      the Stroop Color Test and the Hopkins Verbal Learning Test-Revised (11 min;
      sensitivity = 73%; specificity = 83%); the best 3-test screener included the
      above measures plus the Paced Auditory Serial Addition Test (PASAT; 16 min;
      sensitivity = 86%; specificity = 75%). The addition of Action Fluency to the
      above three tests improved specificity (18 min; sensitivity = 86%; specificity =
      87%). CONCLUSIONS: Combinations of widely accepted neuropsychological tests with
      brief implementation time demonstrated good sensitivity and specificity compared
      to a time intensive neuropsychological test battery. Tests of verbal learning,
      attention/working memory, and processing speed are particularly useful in
      detecting NCI. Utilizing validated, easy to administer, traditional
      neuropsychological tests with established normative data may represent an
      excellent approach to screening for NCI in HIV.

PMID- 23144816
TI  - Conflict of interest disclosures for clinical practice guidelines in the national
      guideline clearinghouse.
AB  - BACKGROUND: Conflict of interest (COI) is an important potential source of bias
      in the development of clinical practice guidelines (CPGs) and high rates of COI
      among guideline authors have been reported in the past. Our objective was to
      report current rates of disclosure and specific author COI across a broad range
      of CPGs and to examine whether CPG characteristics were associated with the
      presence of disclosures and of conflicts. METHODS AND FINDINGS: We selected a
      random sample of 250 CPGs listed in the National Guideline Clearinghouse on
      November 22, 2010, representing approximately a 10% sample of guidelines listed
      in the NGC on that date. We abstracted information on author COI from each CPG
      and examined predictors of the disclosures and COI using a logistic generalized
      estimating equation regression model. 87% of organizations developing guidelines
      had a CPG-specific policy, however, 40% of CPGs did not indicate that they had
      collected disclosures from guideline authors. In addition, 42% of organizations
      that did collect author disclosures did not have those disclosures available in
      the public domain. Of CPGs where we had disclosures for all authors, 60% had one
      or more authors with a conflict. On average, 28% of the authors of CPGs with
      available disclosures had a COI. Guidelines that were published in journals with
      an impact factor greater than 5.0 were more likely to have one or more authors
      with a COI than guidelines not published in journals. CONCLUSIONS: Rates of
      disclosure of author COI and the public availability of that information are
      unacceptably low, however rates of COI among guideline authors may have decreased
      in recent years. Continued efforts are needed to establish and enforce optimal
      COI policies in clinical practice guideline development in order to minimize the
      risk of bias associated with those conflicts.

PMID- 23144817
TI  - Elongation factor 1 alpha1 and genes associated with Usher syndromes are
      downstream targets of GBX2.
AB  - Gbx2 encodes a DNA-binding transcription factor that plays pivotal roles during
      embryogenesis. Gain-and loss-of-function studies in several vertebrate species
      have demonstrated a requirement for Gbx2 in development of the anterior
      hindbrain, spinal cord, inner ear, heart, and neural crest cells. However, the
      target genes through which GBX2 exerts its effects remain obscure. Using
      chromatin immunoprecipitation coupled with direct sequencing (ChIP-Seq) analysis
      in a human prostate cancer cell line, we identified cis-regulatory elements bound
      by GBX2 to provide insight into its direct downstream targets. The analysis
      revealed more than 286 highly significant candidate target genes, falling into
      various functional groups, of which 51% are expressed in the nervous system.
      Several of the top candidate genes include EEF1A1, ROBO1, PLXNA4, SLIT3, NRP1,
      and NOTCH2, as well as genes associated with the Usher syndrome, PCDH15 and
      USH2A, and are plausible candidates contributing to the developmental defects in
      Gbx2(-/-) mice. We show through gel shift analyses that sequences within the
      promoter or introns of EEF1A1, ROBO1, PCDH15, USH2A and NOTCH2, are directly
      bound by GBX2. Consistent with these in vitro results, analyses of Gbx2(-/-)
      embryos indicate that Gbx2 function is required for migration of Robo1-expressing
      neural crest cells out of the hindbrain. Furthermore, we show that GBX2 activates
      transcriptional activity through the promoter of EEF1A1, suggesting that GBX2
      could also regulate gene expression indirectly via EEF1A. Taken together, our
      studies show that GBX2 plays a dynamic role in development and diseases.

PMID- 23144818
TI  - Use of anti-retroviral therapy in tuberculosis patients on second-line anti-TB
      regimens: a systematic review.
AB  - INTRODUCTION: Use of antiretroviral therapy (ART) during treatment of drug
      susceptible tuberculosis (TB) improves survival. However, data from HIV infected
      individuals with drug resistant TB are lacking. Second line TB drugs when
      combined with ART may increase drug interactions and lead to higher rates of
      toxicity and greater noncompliance. This systematic review sought to determine
      the benefit of ART in the setting of second line drug therapy for drug resistant
      TB. METHODS: We included individual patient data from studies that evaluated
      treatment of drug-resistant tuberculosis in HIV-1 infected individuals published
      between January 1980 and December of 2009. We evaluated the effect of ART on
      treatment outcomes, time to smear and culture conversion, and adverse events.
      RESULTS: Ten observational studies, including data from 217 subjects, were
      analyzed. Patients using ART during TB treatment had increased likelihood of cure
      (hazard ratio (HR) 3.4, 95% CI 1.6-7.4) and decreased likelihood of death (HR
      0.4, 95% CI 0.3-0.6) during treatment for drug resistant TB. These associations
      remained significant in patients with a CD4 less than 200 cells/mm(3) and less
      than 50 cells/mm(3), and when correcting for drug resistance pattern.
      LIMITATIONS: We identified only observational studies from which individual
      patient data could be drawn. Limitations in study design, and heterogeneity in a
      number of the outcomes of interest had the potential to introduce bias.
      DISCUSSION: While there are insufficient data to determine if ART use increases
      adverse drug interactions when used with second line TB drugs, ART use during
      treatment of drug resistant TB appears to improve cure rates and decrease risk of
      death. All individuals with HIV appear to benefit from ART use during treatment
      for TB.

PMID- 23144819
TI  - Complement defects in patients with chronic rhinosinusitis.
AB  - The complement system is an important part of our immune system, and complement
      defects lead generally to increased susceptibility to infections and autoimmune
      diseases. We have studied the role of complement activity in relation with
      chronic rhinosinusitis (CRS), and more specifically studied whether complement
      defects collectively predispose individuals for CRS or affect CRS severity. The
      participants comprised 87 CRS patients randomly selected from the general
      population, and a control group of 150 healthy blood donors. The CRS patients
      were diagnosed according to the European Position Paper on Rhinosinusitis and
      nasal Polyps criteria, and severity was evaluated by the Sino-nasal Outcome Test
      22. Serum samples were analysed by ELISA for activity of the respective pathways
      of complement, and subsequently for serum levels of relevant components. We found
      that the frequency of complement defects was significantly higher among CRS
      patients than among healthy control subjects. A majority of Mannan-binding lectin
      deficient CRS patients was observed. The presence of complement defects had no
      influence on the severity of subjective symptoms. Our studies show that defects
      in the complement system collectively may play an immunological role related to
      the development of CRS. However, an association between severity of symptoms and
      presence of complement defects could not be demonstrated.

PMID- 23144820
TI  - Orientation-specificity of adaptation: isotropic adaptation is purely monocular.
AB  - Numerous studies have found that prolonged exposure to grating stimuli reduces
      sensitivity to subsequently presented gratings, most evidently when the
      orientations of the adapting and test patterns are similar. The rate of
      sensitivity loss varies with angular difference indicating both the presence and
      bandwidths of psychophysical 'orientation channels'. Here we study the
      orientation dependency of contrast adaptation measured both monoptically and
      dichoptically. Earlier psychophysical reports show that orientation bandwidths
      are broader at lower spatial frequencies, and we confirm this with a simple von
      Mises model using 0.25 vs. 2 c.p.d. gratings. When a single isotropic
      (orientation invariant) parameter is added to this model, however, we find no
      evidence for any difference in bandwidth with spatial frequency. Consistent with
      cross-orientation masking effects, we find isotropic adaptation to be strongly
      low spatial frequency-biased. Surprisingly, unlike masking, we find that the
      effects of interocular adaptation are purely orientation-tuned, with no evidence
      of isotropic threshold elevation. This dissociation points to isotropic (or
      'cross-orientation') adaptation being an earlier and more magnocellular-like
      process than that which supports orientation-tuned adaptation and suggests that
      isotropic masking and adaptation are likely mediated by separate mechanisms.

PMID- 23144821
TI  - Dioscorea alata attenuates renal interstitial cellular fibrosis by regulating
      Smad- and epithelial-mesenchymal transition signaling pathways.
AB  - Renal interstitial fibrosis is characterized by increased extracellular matrix
      (ECM) synthesis. Epithelial-mesenchymal transition (EMT) in kidneys is driven by
      regulated expression of fibrogenic cytokines such as transforming growth factor
      beta (TGF-beta). Yam, or Dioscorea alata (DA) is an important herb in Chinese
      medicine widely used for the treatment of clinical diabetes mellitus. However,
      the fibrosis regulatory effect of DA is unclear. Thus, we examined TGF-beta
      signaling mechanisms against EMT in rat fibroblast cells (NRK-49F). The
      characterization of DA water-extracts used various methods; after inducing
      cellular fibrosis in NRK-49F cells by treatment with beta-hydroxybutyrate (beta
      HB) (10 mM), we used Western blotting to examine the protein expression in the
      TGF-beta-related signal protein type I and type II TGF-beta receptors, Smads2 and
      Smad3 (Smad2/3), pSmad2 and Smad3 (pSmad2/3), Smads4, Smads7, and EMT markers.
      These markers included E-cadherin, alpha-smooth muscle actin (alpha-SMA), and
      matrix metalloproteinase-2 (MMP-2). Bioactive TGF-beta and fibronectin levels in
      the culture media were determined using ELISA. Expressions of fibronectin and
      Snail transcription factor, an EMT-regulatory transcription factor, were assessed
      by immunofluorescence staining. DA extract dose-dependently (50-200 ug/mL)
      suppressed beta-HB-induced expression of fibronectin in NRK-49F cells
      concomitantly with the inhibition of Smad2/3, pSmad2/3, and Smad4. By contrast,
      Smad7 expression was significantly increased. DA extract caused a decrease in
      alpha-SMA (alpha-smooth muscle actin) and MMP-2 levels, and an increase in E
      cadherin expression. We propose that DA extract might act as a novel fibrosis
      antagonist, which acts partly by down regulating the TGF-beta/smad signaling
      pathway and modulating EMT expression.

PMID- 23144822
TI  - Residential dampness and molds and the risk of developing asthma: a systematic
      review and meta-analysis.
AB  - CONTEXT: Studies from different geographical regions have assessed the relations
      between indoor dampness and mold problems and the risk of asthma, but the
      evidence has been inconclusive. OBJECTIVE: To assess the relations between
      indicators of indoor dampness and mold problems and the risk of developing new
      asthma, and to investigate whether such relations differ according to the type of
      exposure. DATA SOURCES: A systematic literature search of PubMed database from
      1990 through March 2012 and the reference lists of recent reviews and of relevant
      articles identified in our search. STUDY SELECTION: Cohort/longitudinal and
      incident case-control studies assessing the relation between mold/dampness and
      new asthma were included. DATA EXTRACTION: Three authors independently evaluated
      eligible articles and extracted relevant information using a structured form.
      SYNTHESIS: SIXTEEN STUDIES WERE INCLUDED: 11 cohort and 5 incident case-control
      studies. The summary effect estimates (EE) based on the highest and lowest
      estimates for the relation between any exposure and onset of asthma were for the
      highest estimates 1.48 (95% confidence interval [CI] 1.23-1.78, random-effects
      model, Q-statistic 38.75 (16), P = 0.001) ; and for the lowest estimates: 1.27
      (95% CI 1.06-1.53, random-effects model, Q-statistic 38.12 (16), P = 0.000)
      [corrected].The summary effect estimates were significantly elevated for dampness
      (fixed-effects model: EE 1.33, 95% CI 1.12-1.56, Q-statistic 8.22 (9), P =
      0.413), visible mold (random-effects model; EE 1.29, 95% CI 1.04-1.60, 30.30
      (12), P = 0.001), and mold odor (random-effects model; EE 1.73, 95% CI 1.19-2.50,
      Q-statistics 14.85 (8), P = 0.038), but not for water damage (fixed-effects
      model; EE 1.12, 95% CI 0.98-1.27). Heterogeneity was observed in the study
      specific effect estimates. CONCLUSION: The evidence indicates that dampness and
      molds in the home are determinants of developing asthma. The association of the
      presence of visible mold and especially mold odor to the risk of asthma points
      towards mold-related causal agents.

PMID- 23144823
TI  - Identification of an AP2-family protein that is critical for malaria liver stage
      development.
AB  - Liver-stage malaria parasites are a promising target for drugs and vaccines
      against malaria infection. However, little is currently known about gene
      regulation in this stage. In this study, we used the rodent malaria parasite
      Plasmodium berghei and showed that an AP2-family transcription factor, designated
      AP2-L, plays a critical role in the liver-stage development of the parasite. AP2
      L-depleted parasites proliferated normally in blood and in mosquitoes. However,
      the ability of these parasites to infect the liver was approximately 10,000 times
      lower than that of wild-type parasites. In vitro assays showed that the
      sporozoites of these parasites invaded hepatocytes normally but that their
      development stopped in the middle of the liver schizont stage. Expression
      profiling using transgenic P. berghei showed that fluorescent protein-tagged AP2
      L increased rapidly during the liver schizont stage but suddenly disappeared with
      the formation of the mature liver schizont. DNA microarray analysis showed that
      the expression of several genes, including those of parasitophorous vacuole
      membrane proteins, was significantly decreased in the early liver stage of AP2-L
      depleted parasites. Investigation of the targets of this transcription factor
      should greatly promote the exploration of liver-stage antigens and the
      elucidation of the mechanisms of hepatocyte infection by malaria parasites.

PMID- 23144824
TI  - Catching the right wave: evaluating wave energy resources and potential
      compatibility with existing marine and coastal uses.
AB  - Many hope that ocean waves will be a source for clean, safe, reliable and
      affordable energy, yet wave energy conversion facilities may affect marine
      ecosystems through a variety of mechanisms, including competition with other
      human uses. We developed a decision-support tool to assist siting wave energy
      facilities, which allows the user to balance the need for profitability of the
      facilities with the need to minimize conflicts with other ocean uses. Our wave
      energy model quantifies harvestable wave energy and evaluates the net present
      value (NPV) of a wave energy facility based on a capital investment analysis. The
      model has a flexible framework and can be easily applied to wave energy projects
      at local, regional, and global scales. We applied the model and compatibility
      analysis on the west coast of Vancouver Island, British Columbia, Canada to
      provide information for ongoing marine spatial planning, including potential wave
      energy projects. In particular, we conducted a spatial overlap analysis with a
      variety of existing uses and ecological characteristics, and a quantitative
      compatibility analysis with commercial fisheries data. We found that wave power
      and harvestable wave energy gradually increase offshore as wave conditions
      intensify. However, areas with high economic potential for wave energy facilities
      were closer to cable landing points because of the cost of bringing energy ashore
      and thus in nearshore areas that support a number of different human uses. We
      show that the maximum combined economic benefit from wave energy and other uses
      is likely to be realized if wave energy facilities are sited in areas that
      maximize wave energy NPV and minimize conflict with existing ocean uses. Our
      tools will help decision-makers explore alternative locations for wave energy
      facilities by mapping expected wave energy NPV and helping to identify sites that
      provide maximal returns yet avoid spatial competition with existing ocean uses.

PMID- 23144825
TI  - Novel antibacterial activity of beta(2)-microglobulin in human amniotic fluid.
AB  - An antibacterial protein (about 12 kDa) was isolated from human amniotic fluid
      through dialysis, ultrafiltration and C18 reversed-phase HPLC steps. Automated
      Edman degradation showed that the N-terminal sequence of the antibacterial
      protein was NH(2)-Ile-Gln-Arg-Thr-Pro-Lys-Ile-Gln-Val-Tyr-Ser-Arg-His-Pro-Ala-Glu
      Asn-Gly-. The N-terminal sequence of the antibacterial protein was found to be
      identical to that of beta(2)-microglobulin, a component of MHC class I molecules,
      which are present on all nucleated cells. Matrix-assisted laser desorption
      ionization mass spectrometry (MALDI-MS) revealed that the molecular mass of the
      antibacterial protein was 11,631 Da. This antibacterial protein, beta(2)M,
      possessed potent antibacterial activity against pathogenic bacteria. Specially,
      antibacterial activity was observed in potassium buffer, and potassium ion was
      found to be critical for the antibacterial activity. Interestingly, the
      antibacterial action of beta(2)M was associated with dissipation of the
      transmembrane potential, but the protein did not cause damage to the membrane
      that would result in SYTOX green uptake. In addition, stimulation of WISH
      amniotic epithelial cells with the bacterial endotoxin lipopolysaccharide (LPS)
      induced dose-dependent upregulation of beta(2)M mRNA expression. These results
      suggest that beta(2)M contributes to a self-defense response when amniotic cells
      are exposed to pathogens.

PMID- 23144826
TI  - The impact of disulfiram treatment on the reinforcing effects of cocaine: a
      randomized clinical trial.
AB  - BACKGROUND: Clinical trials indicate that disulfiram (250 mg/d) reduces cocaine
      use, though one study found that treatment with lower doses of disulfiram (62.5
      and 125 mg/d) increased cocaine use. We conducted the present study to better
      understand how disulfiram alters the reinforcing effects of cocaine in cocaine
      users. METHODS: Seventeen non-treatment seeking, cocaine-dependent volunteers
      participated in this double-blind, placebo-controlled, laboratory-based study. A
      cross-over design was utilized in which participants received placebo in one
      phase and disulfiram (250 mg/d) in the other. Following three days of study
      medication participants completed two choice sessions. In one they made 10
      choices between receiving an intravenous infusion of saline or money that
      increased in value (US$ 0.05-16) and in the other cocaine (20 mg) or money.
      RESULTS: Participants chose cocaine more than saline under both disulfiram and
      placebo conditions (p<0.05). Unexpectedly, disulfiram increased both the number
      of cocaine and saline infusion choices (p<0.05). We next examined the
      relationship between disulfiram dose and cocaine choices. Disulfiram dose (mg/kg
      bodyweight) was negatively correlated with number of choices for cocaine
      (p<0.05). Disulfiram also enhanced cocaine-induced increases in cardiovascular
      measures (p's<0.05-0.01). CONCLUSIONS: Disulfiram's impact on the reinforcing
      effects of cocaine depends on dose relative to body weight. Our results suggest
      that the use of weight-based medication doses would produce more reliable
      effects, consistent with weight-based dosing used in pediatrics and in
      preclinical research. TRIAL REGISTRATION: Clinicaltrials.gov NCT00729300.

PMID- 23144827
TI  - A jungle in there: bacteria in belly buttons are highly diverse, but predictable.
AB  - The belly button is one of the habitats closest to us, and yet it remains
      relatively unexplored. We analyzed bacteria and arachaea from the belly buttons
      of humans from two different populations sampled within a nation-wide citizen
      science project. We examined bacterial and archaeal phylotypes present and their
      diversity using multiplex pyrosequencing of 16S rDNA libraries. We then tested
      the oligarchy hypothesis borrowed from tropical macroecology, namely that the
      frequency of phylotypes in one sample of humans predicts its frequency in another
      independent sample. We also tested the predictions that frequent phylotypes (the
      oligarchs) tend to be common when present, and tend to be more phylogenetically
      clustered than rare phylotypes. Once rarefied to four hundred reads per sample,
      bacterial communities from belly buttons proved to be at least as diverse as
      communities known from other skin studies (on average 67 bacterial phylotypes per
      belly button). However, the belly button communities were strongly dominated by a
      few taxa: only 6 phylotypes occurred on >80% humans. While these frequent
      bacterial phylotypes (the archaea were all rare) are a tiny part of the total
      diversity of bacteria in human navels (<0.3% of phylotypes), they constitute a
      major portion of individual reads (~1/3), and are predictable among independent
      samples of humans, in terms of both the occurrence and evolutionary relatedness
      (more closely related than randomly drawn equal sets of phylotypes). Thus, the
      hypothesis that "oligarchs" dominate diverse assemblages appears to be supported
      by human-associated bacteria. Although it remains difficult to predict which
      species of bacteria might be found on a particular human, predicting which
      species are most frequent (or rare) seems more straightforward, at least for
      those species living in belly buttons.

PMID- 23144828
TI  - Differential gene expression profile associated with the abnormality of bone
      marrow mesenchymal stem cells in aplastic anemia.
AB  - Aplastic anemia (AA) is generally considered as an immune-mediated bone marrow
      failure syndrome with defective hematopoietic stem cells (HSCs) and marrow
      microenvironment. Previous studies have demonstrated the defective HSCs and
      aberrant T cellular-immunity in AA using a microarray approach. However, little
      is known about the overall specialty of bone marrow mesenchymal stem cells (BM
      MSCs). In the present study, we comprehensively compared the biological features
      and gene expression profile of BM-MSCs between AA patients and healthy
      volunteers. In comparison with healthy controls, BM-MSCs from AA patients showed
      aberrant morphology, decreased proliferation and clonogenic potential and
      increased apoptosis. BM-MSCs from AA patients were susceptible to be induced to
      differentiate into adipocytes but more difficult to differentiate into
      osteoblasts. Consistent with abnormal biological features, a large number of
      genes implicated in cell cycle, cell division, proliferation, chemotaxis and
      hematopoietic cell lineage showed markedly decreased expression in BM-MSCs from
      AA patients. Conversely, more related genes with apoptosis, adipogenesis and
      immune response showed increased expression in BM-MSCs from AA patients. The gene
      expression profile of BM-MSCs further confirmed the abnormal biological
      properties and provided significant evidence for the possible mechanism of the
      destruction of the bone marrow microenvironment in AA.

PMID- 23144829
TI  - An integrated computational approach to rationalize the activity of non-zinc
      binding MMP-2 inhibitors.
AB  - Matrix metalloproteinases are a family of Zn-proteases involved in tissue
      remodeling and in many pathological conditions. Among them MMP-2 is one of the
      most relevant target in anticancer therapy. Commonly, MMP inhibitors contain a
      functional group able to bind the zinc ion and responsible for undesired side
      effects. The discovery of potent and selective MMP inhibitors not bearing a zinc
      binding group is arising for some MMP family members and represents a new
      opportunity to find selective and non toxic inhibitors.In this work we attempted
      to get more insight on the inhibition process of MMP-2 by two non-zinc-binding
      inhibitors, applying a general protocol that combines several computational tools
      (docking, Molecular Dynamics and Quantum Chemical calculations), that all
      together contribute to rationalize experimental inhibition data. Molecular
      Dynamics studies showed both structural and mechanical-dynamical effects produced
      by the ligands not disclosed by docking analysis. Thermodynamic Integration
      provided relative binding free energies consistent with experimentally observed
      activity data. Quantum Chemical calculations of the tautomeric equilibrium
      involving the most active ligand completed the picture of the binding process.
      Our study highlights the crucial role of the specificity loop and suggests that
      enthalpic effect predominates over the entropic one.

PMID- 23144830
TI  - The limits of de novo DNA motif discovery.
AB  - A major challenge in molecular biology is reverse-engineering the cis-regulatory
      logic that plays a major role in the control of gene expression. This program
      includes searching through DNA sequences to identify "motifs" that serve as the
      binding sites for transcription factors or, more generally, are predictive of
      gene expression across cellular conditions. Several approaches have been proposed
      for de novo motif discovery-searching sequences without prior knowledge of
      binding sites or nucleotide patterns. However, unbiased validation is not
      straightforward. We consider two approaches to unbiased validation of discovered
      motifs: testing the statistical significance of a motif using a DNA "background"
      sequence model to represent the null hypothesis and measuring performance in
      predicting membership in gene clusters. We demonstrate that the background models
      typically used are "too null," resulting in overly optimistic assessments of
      significance, and argue that performance in predicting TF binding or expression
      patterns from DNA motifs should be assessed by held-out data, as in predictive
      learning. Applying this criterion to common motif discovery methods resulted in
      universally poor performance, although there is a marked improvement when motifs
      are statistically significant against real background sequences. Moreover, on
      synthetic data where "ground truth" is known, discriminative performance of all
      algorithms is far below the theoretical upper bound, with pronounced "over
      fitting" in training. A key conclusion from this work is that the failure of de
      novo discovery approaches to accurately identify motifs is basically due to
      statistical intractability resulting from the fixed size of co-regulated gene
      clusters, and thus such failures do not necessarily provide evidence that unfound
      motifs are not active biologically. Consequently, the use of prior knowledge to
      enhance motif discovery is not just advantageous but necessary. An implementation
      of the LR and ALR algorithms is available at http://code.google.com/p/likelihood
      ratio-motifs/.

PMID- 23144831
TI  - The head and neck anatomy of sea turtles (Cryptodira: Chelonioidea) and skull
      shape in Testudines.
AB  - BACKGROUND: Sea turtles (Chelonoidea) are a charismatic group of marine reptiles
      that occupy a range of important ecological roles. However, the diversity and
      evolution of their feeding anatomy remain incompletely known.
      METHODOLOGY/PRINCIPAL FINDINGS: Using computed tomography and classical
      comparative anatomy we describe the cranial anatomy in two sea turtles, the
      loggerhead (Caretta caretta) and Kemp's ridley (Lepidochelys kempii), for a
      better understanding of sea turtle functional anatomy and morphological
      variation. In both taxa the temporal region of the skull is enclosed by bone and
      the jaw joint structure and muscle arrangement indicate that palinal jaw movement
      is possible. The tongue is relatively small, and the hyoid apparatus is not as
      conspicuous as in some freshwater aquatic turtles. We find several similarities
      between the muscles of C. caretta and L. kempii, but comparison with other
      turtles suggests only one of these characters may be derived: connection of the
      m. adductor mandibulae internus into the Pars intramandibularis via the
      Zwischensehne. The large fleshy origin of the m. adductor mandibulae externus
      Pars superficialis from the jugal seems to be a characteristic feature of sea
      turtles. CONCLUSIONS/SIGNIFICANCE: In C. caretta and L. kempii the ability to
      suction feed does not seem to be as well developed as that found in some
      freshwater aquatic turtles. Instead both have skulls suited to forceful biting.
      This is consistent with the observation that both taxa tend to feed on relatively
      slow moving but sometimes armoured prey. The broad fleshy origin of the m.
      adductor mandibulae externus Pars superficialis may be linked to thecheek region
      being almost fully enclosed in bone but the relationship is complex.

PMID- 23144832
TI  - A multi-population consensus genetic map reveals inconsistent marker order among
      maps likely attributed to structural variations in the apple genome.
AB  - Genetic maps serve as frameworks for determining the genetic architecture of
      quantitative traits, assessing structure of a genome, as well as aid in pursuing
      association mapping and comparative genetic studies. In this study, a dense
      genetic map was constructed using a high-throughput 1,536 EST-derived SNP
      GoldenGate genotyping platform and a global consensus map established by
      combining the new genetic map with four existing reliable genetic maps of apple.
      The consensus map identified markers with both major and minor conflicts in
      positioning across all five maps. These major inconsistencies among marker
      positions were attributed either to structural variations within the apple
      genome, or among mapping populations, or genotyping technical errors. These also
      highlighted problems in assembly and anchorage of the reference draft apple
      genome sequence in regions with known segmental duplications. Markers common
      across all five apple genetic maps resulted in successful positioning of 2875
      markers, consisting of 2033 SNPs and 843 SSRs as well as other specific markers,
      on the global consensus map. These markers were distributed across all 17 linkage
      groups, with an average of 169+/-33 marker per linkage group and with an average
      distance of 0.70+/-0.14 cM between markers. The total length of the consensus map
      was 1991.38 cM with an average length of 117.14+/-24.43 cM per linkage group. A
      total of 569 SNPs were mapped onto the genetic map, consisting of 140 recombinant
      individuals, from our recently developed apple Oligonucleotide pool assays (OPA).
      The new functional SNPs, along with the dense consensus genetic map, will be
      useful for high resolution QTL mapping of important traits in apple and for
      pursuing comparative genetic studies in Rosaceae.

PMID- 23144834
TI  - Switching dynamics in an interpersonal competition brings about "deadlock"
      synchronization of players.
AB  - In competitive sport game behavior, certain interpersonal patterns of movement
      coordination evolve even though each individual player only intends to exert
      their own strategy to win. To investigate this interpersonal pattern formation
      process, we asked pairs of naive participants to engage in a play-tag game in
      which they had to remove a tag fastened to their partner's hip. Relative phase
      analysis of the players' step towards-away velocities indicated that anti-phase
      synchronization evolved across 10 repetitions of the game. We clarified evolution
      of this synchronization process using a dynamical model with an attractor (at
      relative pi phase) and a repeller (at 0 relative phase) and discuss the self
      organized nature of model and its ability to embody general solution for martial
      art interpersonal coordination.

PMID- 23144833
TI  - Population genetic structure and origins of Native Hawaiians in the multiethnic
      cohort study.
AB  - The population genetic structure of Native Hawaiians has yet to be
      comprehensively studied, and the ancestral origins of Polynesians remain in
      question. In this study, we utilized high-resolution genome-wide SNP data and
      mitochondrial genomes of 148 and 160 Native Hawaiians, respectively, to
      characterize their population structure of the nuclear and mitochondrial genomes,
      ancestral origins, and population expansion. Native Hawaiians, who self-reported
      full Native Hawaiian heritage, demonstrated 78% Native Hawaiian, 11.5% European,
      and 7.8% Asian ancestry with 99% belonging to the B4 mitochondrial haplogroup.
      The estimated proportions of Native Hawaiian ancestry for those who reported
      mixed ancestry (i.e. 75% and 50% Native Hawaiian heritage) were found to be
      consistent with their self-reported heritage. A significant proportion of
      Melanesian ancestry (mean = 32%) was estimated in 100% self-reported Native
      Hawaiians in an ADMIXTURE analysis of Asian, Melanesian, and Native Hawaiian
      populations of K = 2, where K denotes the number of ancestral populations. This
      notable proportion of Melanesian admixture supports the "Slow-Boat" model of
      migration of ancestral Polynesian populations from East Asia to the Pacific
      Islands. In addition, approximately 1,300 years ago a single, strong expansion of
      the Native Hawaiian population was estimated. By providing important insight into
      the underlying population structure of Native Hawaiians, this study lays the
      foundation for future genetic association studies of this U.S. minority
      population.

PMID- 23144835
TI  - A resonance approach to cochlear mechanics.
AB  - BACKGROUND: How does the cochlea analyse sound into its component frequencies? In
      the 1850s Helmholtz thought it occurred by resonance, whereas a century later
      Bekesy's work indicated a travelling wave. The latter answer seemed to settle the
      question, but with the discovery in 1978 that the cochlea emits sound, the
      mechanics of the cochlea was back on the drawing board. Recent studies have
      raised questions about whether the travelling wave, as currently understood, is
      adequate to explain observations. APPROACH: Applying basic resonance principles,
      this paper revisits the question. A graded bank of harmonic oscillators with
      cochlear-like frequencies and quality factors is simultaneously excited, and it
      is found that resonance gives rise to similar frequency responses, group delays,
      and travelling wave velocities as observed by experiment. The overall effect of
      the group delay gradient is to produce a decelerating wave of peak displacement
      moving from base to apex at characteristic travelling wave speeds. The extensive
      literature on chains of coupled oscillators is considered, and the occurrence of
      travelling waves, pseudowaves, phase plateaus, and forced resonance in such
      systems is noted. CONCLUSION AND SIGNIFICANCE: This alternative approach to
      cochlear mechanics shows that a travelling wave can simply arise as an apparently
      moving amplitude peak which passes along a bank of resonators without carrying
      energy. This highlights the possible role of the fast pressure wave and indicates
      how phase delays and group delays of a set of driven harmonic oscillators can
      generate an apparent travelling wave. It is possible to view the cochlea as a
      chain of globally forced coupled oscillators, and this model incorporates
      fundamental aspects of both the resonance and travelling wave theories.

PMID- 23144836
TI  - Cigarette smoke promotes drug resistance and expansion of cancer stem cell-like
      side population.
AB  - It is well known that many patients continue to smoke cigarettes after being
      diagnosed with cancer. Although smoking cessation has typically been presumed to
      possess little therapeutic value for cancer, a growing body of evidence suggests
      that continued smoking is associated with reduced efficacy of treatment and a
      higher incidence of recurrence. We therefore investigated the effect of cigarette
      smoke condensate (CSC) on drug resistance in the lung cancer and head and neck
      cancer cell lines A549 and UMSCC-10B, respectively. Our results showed that CSC
      significantly increased the cellular efflux of doxorubicin and mitoxantrone. This
      was accompanied by membrane localization and increased expression of the multi
      drug transporter ABCG2. The induced efflux of doxorubicin was reversed upon
      addition of the specific ABCG2 inhibitor Fumitremorgin C, confirming the role of
      ABCG2. Treatment with CSC increased the concentration of phosphorylated Akt,
      while addition of the PI3K inhibitor LY294002 blocked doxorubicin extrusion,
      suggesting that Akt activation is required for CSC-induced drug efflux. In
      addition, CSC was found to promote resistance to doxorubicin as determined by MTS
      assays. This CSC-induced doxurbicin-resistance was mitigated by mecamylamine, a
      nicotinic acetylcholine receptor inhibitor, suggesting that nicotine is at least
      partially responsible for the effect of CSC. Lastly, CSC increased the size of
      the side population (SP), which has been linked to a cancer stem cell-like
      phenotype. In summary, CSC promotes chemoresistance via Akt-mediated regulation
      of ABCG2 activity, and may also increase the proportion of cancer stem-like
      cells, contributing to tumor resilience. These findings underscore the importance
      of smoking cessation following a diagnosis of cancer, and elucidate the
      mechanisms of continued smoking that may be detrimental to treatment.

PMID- 23144837
TI  - Genome-wide chromatin remodeling identified at GC-rich long nucleosome-free
      regions.
AB  - To gain deeper insights into principles of cell biology, it is essential to
      understand how cells reorganize their genomes by chromatin remodeling. We
      analyzed chromatin remodeling on next generation sequencing data from resting and
      activated T cells to determine a whole-genome chromatin remodeling landscape. We
      consider chromatin remodeling in terms of nucleosome repositioning which can be
      observed most robustly in long nucleosome-free regions (LNFRs) that are occupied
      by nucleosomes in another cell state. We found that LNFR sequences are either AT
      rich or GC-rich, where nucleosome repositioning was observed much more
      prominently in GC-rich LNFRs - a considerable proportion of them outside promoter
      regions. Using support vector machines with string kernels, we identified a GC
      rich DNA sequence pattern indicating loci of nucleosome repositioning in resting
      T cells. This pattern appears to be also typical for CpG islands. We found out
      that nucleosome repositioning in GC-rich LNFRs is indeed associated with CpG
      islands and with binding sites of the CpG-island-binding ZF-CXXC proteins KDM2A
      and CFP1. That this association occurs prominently inside and also prominently
      outside of promoter regions hints at a mechanism governing nucleosome
      repositioning that acts on a whole-genome scale.

PMID- 23144839
TI  - Word diffusion and climate science.
AB  - As public and political debates often demonstrate, a substantial disjoint can
      exist between the findings of science and the impact it has on the public. Using
      climate-change science as a case example, we reconsider the role of scientists in
      the information-dissemination process, our hypothesis being that important
      keywords used in climate science follow "boom and bust" fashion cycles in public
      usage. Representing this public usage through extraordinary new data on word
      frequencies in books published up to the year 2008, we show that a classic two
      parameter social-diffusion model closely fits the comings and goings of many
      keywords over generational or longer time scales. We suggest that the fashions of
      word usage contributes an empirical, possibly regular, correlate to the impact of
      climate science on society.

PMID- 23144840
TI  - The impact of climate change on indigenous Arabica coffee (Coffea arabica):
      predicting future trends and identifying priorities.
AB  - Precise modelling of the influence of climate change on Arabica coffee is
      limited; there are no data available for indigenous populations of this species.
      In this study we model the present and future predicted distribution of
      indigenous Arabica, and identify priorities in order to facilitate appropriate
      decision making for conservation, monitoring and future research. Using
      distribution data we perform bioclimatic modelling and examine future
      distribution with the HadCM3 climate model for three emission scenarios (A1B,
      A2A, B2A) over three time intervals (2020, 2050, 2080). The models show a
      profoundly negative influence on indigenous Arabica. In a locality analysis the
      most favourable outcome is a c. 65% reduction in the number of pre-existing
      bioclimatically suitable localities, and at worst an almost 100% reduction, by
      2080. In an area analysis the most favourable outcome is a 38% reduction in
      suitable bioclimatic space, and the least favourable a c. 90% reduction, by 2080.
      Based on known occurrences and ecological tolerances of Arabica, bioclimatic
      unsuitability would place populations in peril, leading to severe stress and a
      high risk of extinction. This study establishes a fundamental baseline for
      assessing the consequences of climate change on wild populations of Arabica
      coffee. Specifically, it: (1) identifies and categorizes localities and areas
      that are predicted to be under threat from climate change now and in the short-
      to medium-term (2020-2050), representing assessment priorities for ex situ
      conservation; (2) identifies 'core localities' that could have the potential to
      withstand climate change until at least 2080, and therefore serve as long-term in
      situ storehouses for coffee genetic resources; (3) provides the location and
      characterization of target locations (populations) for on-the-ground monitoring
      of climate change influence. Arabica coffee is confimed as a climate sensitivite
      species, supporting data and inference that existing plantations will be
      neagtively impacted by climate change.

PMID- 23144838
TI  - The prevalence of parasites and pathogens in Asian honeybees Apis cerana in
      China.
AB  - Pathogens and parasites represent significant threats to the health and well
      being of honeybee species that are key pollinators of agricultural crops and
      flowers worldwide. We conducted a nationwide survey to determine the occurrence
      and prevalence of pathogens and parasites in Asian honeybees, Apis cerana, in
      China. Our study provides evidence of infections of A. cerana by pathogenic
      Deformed wing virus (DWV), Black queen cell virus (BQCV), Nosema ceranae, and C.
      bombi species that have been linked to population declines of European honeybees,
      A. mellifera, and bumble bees. However, the prevalence of DWV, a virus that
      causes widespread infection in A. mellifera, was low, arguably a result of the
      greater ability of A. cerana to resist the ectoprasitic mite Varroa destructor,
      an efficient vector of DWV. Analyses of microbial communities from the A. cerana
      digestive tract showed that Nosema infection could have detrimental effects on
      the gut microbiota. Workers infected by N. ceranae tended to have lower bacterial
      quantities, with these differences being significant for the Bifidobacterium and
      Pasteurellaceae bacteria groups. The results of this nationwide screen show that
      parasites and pathogens that have caused serious problems in European honeybees
      can be found in native honeybee species kept in Asia. Environmental changes due
      to new agricultural practices and globalization may facilitate the spread of
      pathogens into new geographic areas. The foraging behavior of pollinators that
      are in close geographic proximity likely have played an important role in
      spreading of parasites and pathogens over to new hosts. Phylogenetic analyses
      provide insights into the movement and population structure of these parasites,
      suggesting a bidirectional flow of parasites among pollinators. The presence of
      these parasites and pathogens may have considerable implications for an observed
      population decline of Asian honeybees.

PMID- 23144841
TI  - In vivo capsular switch in Streptococcus pneumoniae--analysis by whole genome
      sequencing.
AB  - Two multidrug resistant strains of Streptococcus pneumoniae - SV35-T23 (capsular
      type 23F) and SV36-T3 (capsular type 3) were recovered from the nasopharynx of
      two adult patients during an outbreak of pneumococcal disease in a New York
      hospital in 1996. Both strains belonged to the pandemic lineage PMEN1 but they
      differed strikingly in virulence when tested in the mouse model of IP infection:
      as few as 1000 CFU of SV36 killed all mice within 24 hours after inoculation
      while SV35-T23 was avirulent.Whole genome sequencing (WGS) of the two isolates
      was performed (i) to test if these two isolates belonging to the same clonal type
      and recovered from an identical epidemiological scenario only differed in their
      capsular genes? and (ii) to test if the vast difference in virulence between the
      strains was mostly - or exclusively - due to the type III capsule. WGS
      demonstrated extensive differences between the two isolates including over 2500
      single nucleotide polymorphisms in core genes and also differences in 36 genetic
      determinants: 25 of which were unique to SV35-T23 and 11 unique to strain SV36
      T3. Nineteen of these differences were capsular genes and 9 bacteriocin
      genes.Using genetic transformation in the laboratory, the capsular region of SV35
      T23 was replaced by the type 3 capsular genes from SV36-T3 to generate the
      recombinant SV35-T3* which was as virulent as the parental strain SV36-T3* in the
      murine model and the type 3 capsule was the major virulence factor in the
      chinchilla model as well. On the other hand, a careful comparison of strains SV36
      T3 and the laboratory constructed SV35-T3* in the chinchilla model suggested that
      some additional determinants present in SV36 but not in the laboratory
      recombinant may also contribute to the progression of middle ear disease. The
      nature of this determinants remains to be identified.

PMID- 23144842
TI  - Maternal diets trigger sex-specific divergent trajectories of gene expression and
      epigenetic systems in mouse placenta.
AB  - Males and females responses to gestational overnutrition set the stage for
      subsequent sex-specific differences in adult onset non communicable diseases.
      Placenta, as a widely recognized programming agent, contibutes to the underlying
      processes. According to our previous findings, a high-fat diet during gestation
      triggers sex-specific epigenetic alterations within CpG and throughout the
      genome, together with the deregulation of clusters of imprinted genes. We further
      investigated the impact of diet and sex on placental histology, transcriptomic
      and epigenetic signatures in mice. Both basal gene expression and response to
      maternal high-fat diet were sexually dimorphic in whole placentas. Numerous genes
      showed sexually dimorphic expression, but only 11 genes regardless of the diet.
      In line with the key role of genes belonging to the sex chromosomes, 3 of these
      genes were Y-specific and 3 were X-specific. Amongst all the genes that were
      differentially expressed under a high-fat diet, only 16 genes were consistently
      affected in both males and females. The differences were not only quantitative
      but remarkably qualitative. The biological functions and networks of genes
      dysregulated differed markedly between the sexes. Seven genes of the epigenetic
      machinery were dysregulated, due to effects of diet, sex or both, including the Y
      and X-linked histone demethylase paralogues Kdm5c and Kdm5d, which could mark
      differently male and female epigenomes. The DNA methyltransferase cofactor Dnmt3l
      gene expression was affected, reminiscent of our previous observation of changes
      in global DNA methylation. Overall, this striking sexual dimorphism of
      programming trajectories impose a considerable revision of the current dietary
      interventions protocols.

PMID- 23144845
TI  - 25(OH)D(3) affects the maturation and function of mouse bone marrow-derived
      dendritic cells stimulated by Mycobacterium bovis BCG.
AB  - It has been shown that vitamin D deficiency increases an individual's
      susceptibility to tuberculosis (TB). However, very little is known about the
      effect of vitamin D on the immune response to Mycobacterium tuberculosis (M. tb)
      in dendritic cells (DCs). Because DCs play an important role in TB infection, we
      investigated the phenotypic characteristics and functional capabilities of mouse
      bone marrow-derived dendritic cells (BMDCs) after stimulation with Bacillus
      Calmette-Guerin (BCG) in the presence or absence of 25(OH)D(3)(100 nM). Bone
      marrow cells from mice were cultured with GM-CSF (20 ng/ml) and were then treated
      with 25(OH)D(3) for 7 days. On day 6, 5 ug/ml of BCG (>=1.0*10(6) CFU/mg) was
      added to the cells for 24 hours, and on day 7, the non-adherent cells were
      harvested for phenotypic and functional analyses. After incubation with
      25(OH)D(3), the expression levels of MHC-II and CD86 on the surface of the
      dendritic cells (DCs) and the ability of the DCs to stimulate proliferation of
      allogeneic mixed lymphocytes were lower than control cells (p<0.05). Furthermore,
      the level of Interleukin (IL) -4 secreted by the BMDCs in the 25(OH)D(3) culture
      was lower than that in the control culture (p<0.01). However, the BMDCs cultured
      with 25(OH)D(3) produced significantly higher levels of IL-2, IL-6, IL-10 and
      interferon gamma(IFN-gamma) than those in the control culture (p<0.05). These
      findings suggest that 25(OH)D(3) modulates the immune response during
      mycobacterial infection by affecting the maturation and function of DCs.

PMID- 23144843
TI  - Trigeminal ganglion neurons of mice show intracellular chloride accumulation and
      chloride-dependent amplification of capsaicin-induced responses.
AB  - Intracellular Cl(-) concentrations ([Cl(-)](i)) of sensory neurons regulate
      signal transmission and signal amplification. In dorsal root ganglion (DRG) and
      olfactory sensory neurons (OSNs), Cl(-) is accumulated by the Na(+)-K(+)-2Cl(-)
      cotransporter 1 (NKCC1), resulting in a [Cl(-)](i) above electrochemical
      equilibrium and a depolarizing Cl(-) efflux upon Cl(-) channel opening. Here, we
      investigate the [Cl(-)](i) and function of Cl(-) in primary sensory neurons of
      trigeminal ganglia (TG) of wild type (WT) and NKCC1(-/-) mice using
      pharmacological and imaging approaches, patch-clamping, as well as behavioral
      testing. The [Cl(-)](i) of WT TG neurons indicated active NKCC1-dependent Cl(-)
      accumulation. Gamma-aminobutyric acid (GABA)(A) receptor activation induced a
      reduction of [Cl(-)](i) as well as Ca(2+) transients in a corresponding fraction
      of TG neurons. Ca(2+) transients were sensitive to inhibition of NKCC1 and
      voltage-gated Ca(2+) channels (VGCCs). Ca(2+) responses induced by capsaicin, a
      prototypical stimulus of transient receptor potential vanilloid subfamily member
      1 (TRPV1) were diminished in NKCC1(-/-) TG neurons, but elevated under conditions
      of a lowered [Cl(-)](o) suggesting a Cl(-)-dependent amplification of capsaicin
      induced responses. Using next generation sequencing (NGS), we found expression of
      different Ca(2+)-activated Cl(-) channels (CaCCs) in TGs of mice. Pharmacological
      inhibition of CaCCs reduced the amplitude of capsaicin-induced responses of TG
      neurons in Ca(2+) imaging and electrophysiological recordings. In a behavioral
      paradigm, NKCC1(-/-) mice showed less avoidance of the aversive stimulus
      capsaicin. In summary, our results strongly argue for a Ca(2+)-activated Cl(-)
      dependent signal amplification mechanism in TG neurons that requires
      intracellular Cl(-) accumulation by NKCC1 and the activation of CaCCs.

PMID- 23144846
TI  - Identification of intermediate-size non-coding RNAs involved in the UV-induced
      DNA damage response in C. elegans.
AB  - BACKGROUND: A network of DNA damage response (DDR) mechanisms functions
      coordinately to maintain genome integrity and prevent disease. The Nucleotide
      Excision Repair (NER) pathway is known to function in the response to UV-induced
      DNA damage. Although numbers of coding genes and miRNAs have been identified and
      reported to participate in UV-induced DNA damage response (UV-DDR), the precise
      role of non-coding RNAs (ncRNAs) in UV-DDR remains largely unknown.
      METHODOLOGY/PRINCIPAL FINDINGS: We used high-throughput RNA-sequencing (RNA-Seq)
      to discover intermediate-size (70-500 nt) ncRNAs (is-ncRNAs) in C. elegans, using
      the strains of L4 larvae of wild-type (N2), UV-irradiated (N2/UV100) and NER
      deficient mutant (xpa-1), and 450 novel non-coding transcripts were initially
      identified. A customized microarray assay was then applied to examine the
      expression profiles of both novel transcripts and known is-ncRNAs, and 57 UV-DDR
      related is-ncRNA candidates showed expression variations at different levels
      between UV irradiated strains and non- irradiated strains. The top ranked is
      ncRNA candidates with expression differences were further validated by qRT-PCR
      analysis, of them, 8 novel is-ncRNAs were significantly up-regulated after UV
      irradiation. Knockdown of two novel is-ncRNAs, ncRNA317 and ncRNA415, by RNA
      interference, resulted in higher UV sensitivity and significantly decreased
      expression of NER-related genes in C. elegans. CONCLUSIONS/SIGNIFICANCE: The
      discovery of above two novel is-ncRNAs in this study indicated the functional
      roles of is-ncRNAs in the regulation of UV-DDR network, and aided our
      understanding of the significance of ncRNA involvement in the UV-induced DNA
      damage response.

PMID- 23144844
TI  - Phasor fluorescence lifetime microscopy of free and protein-bound NADH reveals
      neural stem cell differentiation potential.
AB  - In the stem cell field there is a lack of non invasive and fast methods to
      identify stem cell's metabolic state, differentiation state and cell-lineage
      commitment. Here we describe a label-free method that uses NADH as an intrinsic
      biomarker and the Phasor approach to Fluorescence Lifetime microscopy to measure
      the metabolic fingerprint of cells. We show that different metabolic states are
      related to different cell differentiation stages and to stem cell bias to
      neuronal and glial fate, prior the expression of lineage markers. Our data
      demonstrate that the NADH FLIM signature distinguishes non-invasively neurons
      from undifferentiated neural progenitor and stem cells (NPSCs) at two different
      developmental stages (E12 and E16). NPSCs follow a metabolic trajectory from a
      glycolytic phenotype to an oxidative phosphorylation phenotype through different
      stages of differentiation. NSPCs are characterized by high free/bound NADH ratio,
      while differentiated neurons are characterized by low free/bound NADH ratio. We
      demonstrate that the metabolic signature of NPSCs correlates with their
      differentiation potential, showing that neuronal progenitors and glial
      progenitors have a different free/bound NADH ratio. Reducing conditions in NPSCs
      correlates with their neurogenic potential, while oxidative conditions correlate
      with glial potential. For the first time we show that FLIM NADH metabolic
      fingerprint provides a novel, and quantitative measure of stem cell potential and
      a label-free and non-invasive means to identify neuron- or glial- biased
      progenitors.

PMID- 23144847
TI  - Persistent symmetry frustration in pollen tubes.
AB  - Pollen tubes are extremely rapidly growing plant cells whose morphogenesis is
      determined by spatial gradients in the biochemical composition of the cell wall.
      We investigate the hypothesis (MP) that the distribution of the local mechanical
      properties of the wall, corresponding to the change of the radial symmetry along
      the axial direction, may lead to growth oscillations in pollen tubes. We claim
      that the experimentally observed oscillations originate from the symmetry change
      at the transition zone, where both intervening symmetries (cylindrical and
      spherical) meet. The characteristic oscillations between resonating symmetries at
      a given (constant) turgor pressure and a gradient of wall material constants may
      be identified with the observed growth-cycles in pollen tubes.

PMID- 23144848
TI  - Measurement and correction of microscopic head motion during magnetic resonance
      imaging of the brain.
AB  - Magnetic resonance imaging (MRI) is a widely used method for non-invasive study
      of the structure and function of the human brain. Increasing magnetic field
      strengths enable higher resolution imaging; however, long scan times and high
      motion sensitivity mean that image quality is often limited by the involuntary
      motion of the subject. Prospective motion correction is a technique that
      addresses this problem by tracking head motion and continuously updating the
      imaging pulse sequence, locking the imaging volume position and orientation
      relative to the moving brain. The accuracy and precision of current MR-compatible
      tracking systems and navigator methods allows the quantification and correction
      of large-scale motion, but not the correction of very small involuntary movements
      in six degrees of freedom. In this work, we present an MR-compatible tracking
      system comprising a single camera and a single 15 mm marker that provides
      tracking precision in the order of 10 m and 0.01 degrees. We show preliminary
      results, which indicate that when used for prospective motion correction, the
      system enables improvement in image quality at both 3 T and 7 T, even in
      experienced and cooperative subjects trained to remain motionless during imaging.
      We also report direct observation and quantification of the mechanical
      ballistocardiogram (BCG) during simultaneous MR imaging. This is particularly
      apparent in the head-feet direction, with a peak-to-peak displacement of 140 m.

PMID- 23144849
TI  - Distinct contributions of the dorsolateral prefrontal and orbitofrontal cortex
      during emotion regulation.
AB  - The lateral prefrontal and orbitofrontal cortices have both been implicated in
      emotion regulation, but their distinct roles in regulation of negative emotion
      remain poorly understood. To address this issue we enrolled 58 participants in an
      fMRI study in which participants were instructed to reappraise both negative and
      neutral stimuli. This design allowed us to separately study activations
      reflecting cognitive processes associated with reappraisal in general and
      activations specifically related to reappraisal of negative emotion. Our results
      confirmed that both the dorsolateral prefrontal cortex (DLPFC) and the lateral
      orbitofrontal cortex (OFC) contribute to emotion regulation through reappraisal.
      However, activity in the DLPFC was related to reappraisal independently of
      whether negative or neutral stimuli were reappraised, whereas the lateral OFC was
      uniquely related to reappraisal of negative stimuli. We suggest that relative to
      the lateral OFC, the DLPFC serves a more general role in emotion regulation,
      perhaps by reflecting the cognitive demand that is inherent to the regulation
      task.

PMID- 23144850
TI  - Medical students' attitudes towards overweight and obesity.
AB  - OBJECTIVE: Studies from the USA have identified medical students as a major
      source of stigmatizing attitudes towards overweight and obese individuals. As
      data from Europe is scarce, medical students' attitudes were investigated at the
      University of Leipzig in Leipzig, Germany. DESIGN: Cross-sectional survey
      containing an experimental manipulation consisting of a pair of vignettes
      depicting an obese and a normal weight 42-year-old woman, respectively. Vignettes
      were followed by the Fat Phobia Scale (FPS), a semantic differential assessing
      weight related attitudes. In case of the overweight vignette a panel of questions
      on causal attribution for the overweight preceded administration of the FPS.
      SUBJECTS: 671 medical students were enrolled at the University of Leipzig from
      May to June 2011. RESULTS: The overweight vignette was rated significantly more
      negative than the normal weight vignette (mean FPS score 3.65+/-0.45 versus
      2.54+/-0.38, p<0.001). A higher proportion of students had negative attitudes
      towards the overweight as compared to the normal weight individual (98.9% versus
      53.7%, p<0.001). A "positive energy balance" was perceived as the most relevant
      cause for the overweight, followed by "negligent personality trait", "societal
      and social environment" and "biomedical causes". Attributing a "positive energy
      balance" or "negligent personality trait" as relevant cause for the overweight
      was positively associated with negative attitudes. CONCLUSION: The results of
      this study confirm and complement findings from other countries, mainly the USA,
      and indicate that weight bias in the health care setting may be a global issue.
      Stigmatizing attitudes towards overweight and obesity are prevalent among a
      sample of medical students at the University of Leipzig. Negative attitudes arise
      on the basis of holding the individual accountable for the excess weight. They
      call for bringing the topic of overweight and obesity more into the focus of the
      medical curriculum and for enhancing medical students' awareness of the complex
      aetiology of this health condition.

PMID- 23144851
TI  - Collective almost synchronisation in complex networks.
AB  - This work introduces the phenomenon of Collective Almost Synchronisation (CAS),
      which describes a universal way of how patterns can appear in complex networks
      for small coupling strengths. The CAS phenomenon appears due to the existence of
      an approximately constant local mean field and is characterised by having nodes
      with trajectories evolving around periodic stable orbits. Common notion based on
      statistical knowledge would lead one to interpret the appearance of a local
      constant mean field as a consequence of the fact that the behaviour of each node
      is not correlated to the behaviours of the others. Contrary to this common
      notion, we show that various well known weaker forms of synchronisation (almost,
      time-lag, phase synchronisation, and generalised synchronisation) appear as a
      result of the onset of an almost constant local mean field. If the memory is
      formed in a brain by minimising the coupling strength among neurons and
      maximising the number of possible patterns, then the CAS phenomenon is a
      plausible explanation for it.

PMID- 23144853
TI  - Evaluating spatial-temporal dynamics of net primary productivity of different
      forest types in northeastern China based on improved FORCCHN.
AB  - An improved individual-based forest ecosystem carbon budget model for China
      (FORCCHN) was applied to investigate the spatial-temporal dynamics of net primary
      productivity of different forest types in northeastern China. In this study, the
      forests of northeastern China were categorized into four ecological types
      according to their habitats and generic characteristics (evergreen broadleaf
      forest, deciduous broadleaf forest, evergreen needleleaf forest and deciduous
      needleleaf forest). The results showed that distribution and change of forest NPP
      in northeastern China were related to the different forest types. From 1981 to
      2002, among the forest types in northeastern China, per unit area NPP and total
      NPP of deciduous broadleaf forest were the highest, with the values of 729.4
      gC/(m(2)*yr) and 106.0 TgC/yr, respectively, followed by mixed broadleaf-
      needleleaf forest, deciduous needleleaf forest and evergreen needleleaf forest.
      From 1981 to 2002, per unit area NPP and total NPP of different forest types in
      northeastern China exhibited significant trends of interannual increase, and
      rapid increase was found between the 1980s and 1990s. The contribution of the
      different forest type's NPP to total NPP in northeastern China was clearly
      different. The greatest was deciduous broadleaf forest, followed by mixed
      broadleaf- needleleaf forest and deciduous needleleaf forest. The smallest was
      evergreen needleleaf forest. Spatial difference in NPP between different forest
      types was remarkable. High NPP values of deciduous needleleaf forest, mixed
      broadleaf- needleleaf forest and deciduous broadleaf forest were found in the
      Daxing'anling region, the southeastern of Xiaoxing'anling and Jilin province, and
      the Changbai Mountain, respectively. However, no regional differences were found
      for evergreen needleleaf NPP. This study provided not only an estimation NPP of
      different forest types in northeastern China but also a useful methodology for
      estimating forest carbon storage at regional and global levels.

PMID- 23144852
TI  - Approaches towards DNA vaccination against a skin ciliate parasite in fish.
AB  - Rainbow trout (Oncorhynchus mykiss) were immunized with plasmid DNA vaccine
      constructs encoding selected antigens from the parasite Ichthyophthirius
      multifiliis. Two immobilization antigens (I-ags) and one cysteine protease were
      tested as genetic vaccine antigen candidates. Antigenicity was evaluated by
      immunostaining of transfected fish cells using I-ag specific mono- and polyclonal
      antibodies. I. multifiliis specific antibody production, regulation of immune
      relevant genes and/or protection in terms of parasite burden or mortality was
      measured to evaluate the induced immune response in vaccinated fish. Apart from
      intramuscular injection, needle free injection and gene gun delivery were tested
      as alternative administration techniques. For the I-ags the complement protein
      fragment C3d and the termini of the viral haemorrhagic septicaemia virus
      glyco(G)protein (VHSV G) were tested as opsonisation and cellular localisation
      mediators, respectively, while the full length viral G protein was tested as
      molecular adjuvant. Expression of I-ags in transfected fish cells was
      demonstrated for several constructs and by immunohistochemistry it was possible
      to detect expression of a secreted form of the Iag52B in the muscle cells of
      injected fish. Up-regulations of mRNA coding for IgM, MHC I, MHC II and TCR beta,
      respectively, were observed in muscle tissue at the injection site in selected
      trials. In the spleen up-regulations were found for IFN-gamma and IL-10. The
      highest up-regulations were seen following co-administration of I-ag and cysteine
      protease plasmid constructs. This correlated with a slight elevation of an I.
      multifiliis specific antibody response. However, in spite of detectable antigen
      expression and immune reactions, none of the tested vaccination strategies
      provided significant protection. This might suggest an insufficiency of DNA
      vaccination alone to trigger protective mechanisms against I. multifiliis or that
      other or additional parasite antigens are required for such a vaccine to be
      successful.

PMID- 23144854
TI  - Association of GSTP1 Ile105Val polymorphism and risk of head and neck cancers: a
      meta-analysis of 28 case-control studies.
AB  - BACKGROUND AND AIMS: The Glutathione S-transferase P1 (GSTP1) polymorphism have
      been considered a risk modifier for developing head and neck cancer (HNC) in many
      studies; however, the results of such studies are inconsistent. The aim of this
      study was to evaluate the possible association between the GSTP1 Ile105Val
      polymorphism and risk of HNC. METHOD: We performed a search in the relevant
      electronic database and a meta-analysis based on 28 published case-control
      studies that included 6,404 cases and 6,523 controls. To take into account the
      possibility of heterogeneity across the studies, a Chi-square based I(2)
      statistic test was performed. Crude pooled odds ratios (ORs) with 95% confidence
      intervals (CIs) were assessed using both fixed-effects and random-effects models.
      RESULTS: The results of this meta-analysis showed that the GSTP1 Ile105Val
      polymorphism was not significantly associated with risk of HNC in the overall
      study population (pooled OR 1.00, 95% CI 0.92-1.09) or in subgroup analyses
      stratified by ethnicity, sample size, tumor site or publication year. Moreover,
      substantial evidence of heterogeneity among the studies was observed. Publication
      year was identified as the main cause of heterogeneity. CONCLUSION: This meta
      analysis does not support a significant association between the GSTP1 Ile105Val
      polymorphism and risk of HNC.

PMID- 23144855
TI  - Social rewards enhance offline improvements in motor skill.
AB  - Motor skill memory is first encoded online in a fragile form during practice and
      then converted into a stable form by offline consolidation, which is the
      behavioral stage critical for successful learning. Praise, a social reward, is
      thought to boost motor skill learning by increasing motivation, which leads to
      increased practice. However, the effect of praise on consolidation is unknown.
      Here, we tested the hypothesis that praise following motor training directly
      facilitates skill consolidation. Forty-eight healthy participants were trained on
      a sequential finger-tapping task. Immediately after training, participants were
      divided into three groups according to whether they received praise for their own
      training performance, praise for another participant's performance, or no praise.
      Participants who received praise for their own performance showed a significantly
      higher rate of offline improvement relative to other participants when performing
      a surprise recall test of the learned sequence. On the other hand, the average
      performance of the novel sequence and randomly-ordered tapping did not differ
      between the three experimental groups. These results are the first to indicate
      that praise-related improvements in motor skill memory are not due to a feedback
      incentive mechanism, but instead involve direct effects on the offline
      consolidation process.

PMID- 23144856
TI  - A personalized BEST: characterization of latent clinical classes of nonischemic
      heart failure that predict outcomes and response to bucindolol.
AB  - BACKGROUND: Heart failure patients with reduced ejection fraction (HFREF) are
      heterogenous, and our ability to identify patients likely to respond to therapy
      is limited. We present a method of identifying disease subtypes using high
      dimensional clinical phenotyping and latent class analysis that may be useful in
      personalizing prognosis and treatment in HFREF. METHODS: A total of 1121 patients
      with nonischemic HFREF from the beta-blocker Evaluation of Survival Trial were
      categorized according to 27 clinical features. Latent class analysis was used to
      generate two latent class models, LCM A and B, to identify HFREF subtypes. LCM A
      consisted of features associated with HF pathogenesis, whereas LCM B consisted of
      markers of HF progression and severity. The Seattle Heart Failure Model (SHFM)
      Score was also calculated for all patients. Mortality, improvement in left
      ventricular ejection fraction (LVEF) defined as an increase in LVEF >=5% and a
      final LVEF of 35% after 12 months, and effect of bucindolol on both outcomes were
      compared across HFREF subtypes. Performance of models that included a combination
      of LCM subtypes and SHFM scores towards predicting mortality and LVEF response
      was estimated and subsequently validated using leave-one-out cross-validation and
      data from the Multicenter Oral Carvedilol Heart Failure Assessment Trial.
      RESULTS: A total of 6 subtypes were identified using LCM A and 5 subtypes using
      LCM B. Several subtypes resembled familiar clinical phenotypes. Prognosis,
      improvement in LVEF, and the effect of bucindolol treatment differed
      significantly between subtypes. Prediction improved with addition of both latent
      class models to SHFM for both 1-year mortality and LVEF response outcomes.
      CONCLUSIONS: The combination of high-dimensional phenotyping and latent class
      analysis identifies subtypes of HFREF with implications for prognosis and
      response to specific therapies that may provide insight into mechanisms of
      disease. These subtypes may facilitate development of personalized treatment
      plans.

PMID- 23144857
TI  - A simple sign for recognizing off-axis OCT measurement beam placement in the
      context of multicentre studies.
AB  - PURPOSE: Optical coherence tomography (OCT) allows quantification of the
      thickness of the retinal nerve fibre layer (RNFL) thickness, a potential
      biomarker for neurodegeneration. The estimated annual RNFL loss in multiple
      sclerosis amounts to 2 MUm using time domain OCT. The recognition of measurement
      artifacts exceeding this limit is relevant for the successful use of OCT as a
      secondary outcome measure in clinical trials. METHODS: Prospective study design.
      An exploratory pilot study (ring and volume scans) followed by a cohort study
      (1,980 OCT ring scans). The OCT measurement beam was placed off-axis to the left,
      right, top and bottom of the subjects pupil and RNFL thickness of these scans
      were compared to the centrally placed reference scans. RESULTS: Off-axis
      placement of the OCT measurement beam resulted in significant artifacts in RNFL
      thickness measurements (95%CI 9MUm, maximal size of error 42MUm). Off-axis
      placement gave characteristic patterns of the OCT live images which are not
      necessarily saved for review. Off-axis placement also causes regional
      inhomogeneity of reflectivity in the outer nuclear (ONL) and outer plexiform
      layers (OPL) which remains visible on scans saved for review. CONCLUSION: Off
      axis beam placement introduces measurement artifacts at a magnitude which may
      mask recognition of RNFL loss due to neurodegeneration in multiple sclerosis. The
      resulting pattern in the OCT live image can only be recognised by the technician
      capturing the scans. Once the averaged scans have been aligned this pattern is
      lost. Retrospective identification of this artifact is however possible by
      presence of regional inhomogeneity of ONL/OPL reflectivity. This simple and
      robust sign may be considered for quality control criteria in the setting of
      multicentre OCT studies. The practical advice of this study is to keep the OCT
      image in the acquisition window horizontally aligned whenever possible.

PMID- 23144858
TI  - Embryonic morphogen nodal promotes breast cancer growth and progression.
AB  - Breast cancers expressing human embryonic stem cell (hESC)-associated genes are
      more likely to progress than well-differentiated cancers and are thus associated
      with poor patient prognosis. Elevated proliferation and evasion of growth control
      are similarly associated with disease progression, and are classical hallmarks of
      cancer. In the current study we demonstrate that the hESC-associated factor Nodal
      promotes breast cancer growth. Specifically, we show that Nodal is elevated in
      aggressive MDA-MB-231, MDA-MB-468 and Hs578t human breast cancer cell lines,
      compared to poorly aggressive MCF-7 and T47D breast cancer cell lines. Nodal
      knockdown in aggressive breast cancer cells via shRNA reduces tumour incidence
      and significantly blunts tumour growth at primary sites. In vitro, using Trypan
      Blue exclusion assays, Western blot analysis of phosphorylated histone H3 and
      cleaved caspase-9, and real time RT-PCR analysis of BAX and BCL2 gene expression,
      we demonstrate that Nodal promotes expansion of breast cancer cells, likely via a
      combinatorial mechanism involving increased proliferation and decreased
      apopotosis. In an experimental model of metastasis using beta-glucuronidase
      (GUSB)-deficient NOD/SCID/mucopolysaccharidosis type VII (MPSVII) mice, we show
      that although Nodal is not required for the formation of small (<100 cells)
      micrometastases at secondary sites, it supports an elevated
      proliferation:apoptosis ratio (Ki67:TUNEL) in micrometastatic lesions. Indeed, at
      longer time points (8 weeks), we determined that Nodal is necessary for the
      subsequent development of macrometastatic lesions. Our findings demonstrate that
      Nodal supports tumour growth at primary and secondary sites by increasing the
      ratio of proliferation:apoptosis in breast cancer cells. As Nodal expression is
      relatively limited to embryonic systems and cancer, this study establishes Nodal
      as a potential tumour-specific target for the treatment of breast cancer.

PMID- 23144859
TI  - Integrative analysis reveals relationships of genetic and epigenetic alterations
      in osteosarcoma.
AB  - BACKGROUND: Osteosarcomas are the most common non-haematological primary
      malignant tumours of bone, and all conventional osteosarcomas are high-grade
      tumours showing complex genomic aberrations. We have integrated genome-wide
      genetic and epigenetic profiles from the EuroBoNeT panel of 19 human osteosarcoma
      cell lines based on microarray technologies. PRINCIPAL FINDINGS: The cell lines
      showed complex patterns of DNA copy number changes, where genomic copy number
      gains were significantly associated with gene-rich regions and losses with gene
      poor regions. By integrating the datasets, 350 genes were identified as having
      two types of aberrations (gain/over-expression, hypo-methylation/over-expression,
      loss/under-expression or hyper-methylation/under-expression) using a recurrence
      threshold of 6/19 (>30%) cell lines. The genes showed in general alterations in
      either DNA copy number or DNA methylation, both within individual samples and
      across the sample panel. These 350 genes are involved in embryonic skeletal
      system development and morphogenesis, as well as remodelling of extracellular
      matrix. The aberrations of three selected genes, CXCL5, DLX5 and RUNX2, were
      validated in five cell lines and five tumour samples using PCR techniques.
      Several genes were hyper-methylated and under-expressed compared to normal
      osteoblasts, and expression could be reactivated by demethylation using 5-Aza-2'
      deoxycytidine treatment for four genes tested; AKAP12, CXCL5, EFEMP1 and IL11RA.
      Globally, there was as expected a significant positive association between gain
      and over-expression, loss and under-expression as well as hyper-methylation and
      under-expression, but gain was also associated with hyper-methylation and under
      expression, suggesting that hyper-methylation may oppose the effects of increased
      copy number for detrimental genes. CONCLUSIONS: Integrative analysis of genome
      wide genetic and epigenetic alterations identified dependencies and relationships
      between DNA copy number, DNA methylation and mRNA expression in osteosarcomas,
      contributing to better understanding of osteosarcoma biology.

PMID- 23144860
TI  - Single cell analysis of yeast replicative aging using a new generation of
      microfluidic device.
AB  - A major limitation to yeast aging study has been the inability to track mother
      cells and observe molecular markers during the aging process. The traditional
      lifespan assay relies on manual micro-manipulation to remove daughter cells from
      the mother, which is laborious, time consuming, and does not allow long term
      tracking with high resolution microscopy. Recently, we have developed a
      microfluidic system capable of retaining mother cells in the microfluidic
      chambers while removing daughter cells automatically, making it possible to
      observe fluorescent reporters in single cells throughout their lifespan. Here we
      report the development of a new generation of microfluidic device that overcomes
      several limitations of the previous system, making it easier to fabricate and
      operate, and allowing functions not possible with the previous design. The basic
      unit of the device consists of microfluidic channels with pensile columns that
      can physically trap the mother cells while allowing the removal of daughter cells
      automatically by the flow of the fresh media. The whole microfluidic device
      contains multiple independent units operating in parallel, allowing simultaneous
      analysis of multiple strains. Using this system, we have reproduced the lifespan
      curves for the known long and short-lived mutants, demonstrating the power of the
      device for automated lifespan measurement. Following fluorescent reporters in
      single mother cells throughout their lifespan, we discovered a surprising change
      of expression of the translation elongation factor TEF2 during aging, suggesting
      altered translational control in aged mother cells. Utilizing the capability of
      the new device to trap mother-daughter pairs, we analyzed mother-daughter
      inheritance and found age dependent asymmetric partitioning of a general stress
      response reporter between mother and daughter cells.

PMID- 23144861
TI  - Next generation sequencing to define prokaryotic and fungal diversity in the
      bovine rumen.
AB  - A combination of Sanger and 454 sequences of small subunit rRNA loci were used to
      interrogate microbial diversity in the bovine rumen of 12 cows consuming a forage
      diet. Observed bacterial species richness, based on the V1-V3 region of the 16S
      rRNA gene, was between 1,903 to 2,432 species-level operational taxonomic units
      (OTUs) when 5,520 reads were sampled per animal. Eighty percent of species-level
      OTUs were dominated by members of the order Clostridiales, Bacteroidales,
      Erysipelotrichales and unclassified TM7. Abundance of Prevotella species varied
      widely among the 12 animals. Archaeal species richness, also based on 16S rRNA,
      was between 8 and 13 OTUs, representing 5 genera. The majority of archaeal OTUs
      (84%) found in this study were previously observed in public databases with only
      two new OTUs discovered. Observed rumen fungal species richness, based on the 18S
      rRNA gene, was between 21 and 40 OTUs with 98.4-99.9% of OTUs represented by more
      than one read, using Good's coverage. Examination of the fungal community
      identified numerous novel groups. Prevotella and Tannerella were overrepresented
      in the liquid fraction of the rumen while Butyrivibrio and Blautia were
      significantly overrepresented in the solid fraction of the rumen. No statistical
      difference was observed between the liquid and solid fractions in biodiversity of
      archaea and fungi. The survey of microbial communities and analysis of cross
      domain correlations suggested there is a far greater extent of microbial
      diversity in the bovine rumen than previously appreciated, and that next
      generation sequencing technologies promise to reveal novel species, interactions
      and pathways that can be studied further in order to better understand how rumen
      microbial community structure and function affects ruminant feed efficiency,
      biofuel production, and environmental impact.

PMID- 23144862
TI  - Bilayer elasticity at the nanoscale: the need for new terms.
AB  - Continuum elastic models that account for membrane thickness variations are
      especially useful in the description of nanoscale deformations due to the
      presence of membrane proteins with hydrophobic mismatch. We show that terms
      involving the gradient and the Laplacian of the area per lipid are significant
      and must be retained in the effective Hamiltonian of the membrane. We reanalyze
      recent numerical data, as well as experimental data on gramicidin channels, in
      light of our model. This analysis yields consistent results for the term stemming
      from the gradient of the area per molecule. The order of magnitude we find for
      the associated amplitude, namely 13-60 mN/m, is in good agreement with the 25
      mN/m contribution of the interfacial tension between water and the hydrophobic
      part of the membrane. The presence of this term explains a systematic variation
      in previously published numerical data.

PMID- 23144864
TI  - Rapid and sensitive microRNA detection with laminar flow-assisted dendritic
      amplification on power-free microfluidic chip.
AB  - Detection of microRNAs, small noncoding single-stranded RNAs, is one of the key
      topics in the new generation of cancer research because cancer in the human body
      can be detected or even classified by microRNA detection. This report shows rapid
      and sensitive microRNA detection using a power-free microfluidic device, which is
      driven by degassed poly(dimethylsiloxane), thus eliminating the need for an
      external power supply. MicroRNA is detected by sandwich hybridization, and the
      signal is amplified by laminar flow-assisted dendritic amplification. This method
      allows us to detect microRNA of specific sequences at a limit of detection of 0.5
      pM from a 0.5 uL sample solution with a detection time of 20 min. Together with
      the advantages of self-reliance of this device, this method might contribute
      substantially to future point-of-care early-stage cancer diagnosis.

PMID- 23144865
TI  - An experimental test of the accumulated copying error model of cultural mutation
      for Acheulean handaxe size.
AB  - Archaeologists interested in explaining changes in artifact morphology over long
      time periods have found it useful to create models in which the only source of
      change is random and unintentional copying error, or 'cultural mutation'. These
      models can be used as null hypotheses against which to detect non-random
      processes such as cultural selection or biased transmission. One proposed
      cultural mutation model is the accumulated copying error model, where individuals
      attempt to copy the size of another individual's artifact exactly but make small
      random errors due to physiological limits on the accuracy of their perception.
      Here, we first derive the model within an explicit mathematical framework,
      generating the predictions that multiple independently-evolving artifact chains
      should diverge over time such that their between-chain variance increases while
      the mean artifact size remains constant. We then present the first experimental
      test of this model in which 200 participants, split into 20 transmission chains,
      were asked to faithfully copy the size of the previous participant's handaxe
      image on an iPad. The experimental findings supported the model's prediction that
      between-chain variance should increase over time and did so in a manner
      quantitatively in line with the model. However, when the initial size of the
      image that the participants resized was larger than the size of the image they
      were copying, subjects tended to increase the size of the image, resulting in the
      mean size increasing rather than staying constant. This suggests that items of
      material culture formed by reductive vs. additive processes may mutate
      differently when individuals attempt to replicate faithfully the size of
      previously-produced artifacts. Finally, we show that a dataset of 2601 Acheulean
      handaxes shows less variation than predicted given our empirically measured
      copying error variance, suggesting that other processes counteracted the
      variation in handaxe size generated by perceptual cultural mutation.

PMID- 23144863
TI  - Is wetter better? An evaluation of over-the-counter personal lubricants for
      safety and anti-HIV-1 activity.
AB  - Because lubricants may decrease trauma during coitus, it is hypothesized that
      they could aid in the prevention of HIV acquisition. Therefore, safety and anti
      HIV-1 activity of over-the-counter (OTC) aqueous- (n = 10), lipid- (n = 2), and
      silicone-based (n = 2) products were tested. The rheological properties of the
      lipid-based lubricants precluded testing with the exception of explant safety
      testing. Six aqueous-based gels were hyperosmolar, two were nearly iso-osmolar,
      and two were hypo-osmolar. Evaluation of the panel of products showed Gynol II (a
      spermicidal gel containing 2% nonoxynol-9), KY Jelly, and Replens were toxic to
      Lactobacillus. Two nearly iso-osmolar aqueous- and both silicone-based gels were
      not toxic toward epithelial cell lines or ectocervical or colorectal explant
      tissues. Hyperosmolar lubricants demonstrated reduction of tissue viability and
      epithelial fracture/sloughing while the nearly iso-osmolar and silicon-based
      lubricants showed no significant changes in tissue viability or epithelial
      modifications. While most of the lubricants had no measurable anti-HIV-1
      activity, three lubricants which retained cell viability did demonstrate modest
      anti-HIV-1 activity in vitro. To determine if this would result in protection of
      mucosal tissue or conversely determine if the epithelial damage associated with
      the hyperosmolar lubricants increased HIV-1 infection ex vivo, ectocervical
      tissue was exposed to selected lubricants and then challenged with HIV-1. None of
      the lubricants that had a moderate to high therapeutic index protected the
      mucosal tissue. These results show hyperosmolar lubricant gels were associated
      with cellular toxicity and epithelial damage while showing no anti-viral
      activity. The two iso-osmolar lubricants, Good Clean Love and PRE, and both
      silicone-based lubricants, Female Condom 2 lubricant and Wet Platinum, were the
      safest in our testing algorithm.

PMID- 23144866
TI  - Targeting COX-2/PGE(2) pathway in HIPK2 knockdown cancer cells: impact on
      dendritic cell maturation.
AB  - BACKGROUND: Homeodomain-interacting protein kinase 2 (HIPK2) is a multifunctional
      protein that exploits its kinase activity to modulate key molecular pathways in
      cancer to restrain tumor growth and induce response to therapies. For instance,
      HIPK2 knockdown induces upregulation of oncogenic hypoxia-inducible factor-1 (HIF
      1) activity leading to a constitutive hypoxic and angiogenic phenotype with
      increased tumor growth in vivo. HIPK2 inhibition, therefore, releases pathways
      leading to production of pro-inflammatory molecules such as vascular endothelial
      growth factor (VEGF) or prostaglandin E2 (PGE(2)). Tumor-produced inflammatory
      mediators other than promote tumour growth and vascular development may permit
      evasion of anti-tumour immune responses. Thus, dendritic cells (DCs) dysfunction
      induced by tumor-produced molecules, may allow tumor cells to escape
      immunosurveillance. Here we evaluated the molecular mechanism of PGE(2)
      production after HIPK2 depletion and how to modulate it. METHODOLOGY/PRINCIPAL
      FINDINGS: We show that HIPK2 knockdown in colon cancer cells resulted in
      cyclooxygenase-2 (COX-2) upregulation and COX-2-derived PGE(2) generation. At
      molecular level, COX-2 upregulation depended on HIF-1 activity. We previously
      reported that zinc treatment inhibits HIF-1 activity. Here, zinc supplementation
      to HIPK2 depleted cells inhibited HIF-1-induced COX-2 expression and PGE(2)/VEGF
      production. At translational level, while conditioned media of both siRNA control
      and HIPK2 depleted cells inhibited DCs maturation, conditioned media of only zinc
      treated HIPK2 depleted cells efficiently restored DCs maturation, seen as the
      expression of co-stimulatory molecules CD80 and CD86, cytokine IL-10 release, and
      STAT3 phosphorylation. CONCLUSION/SIGNIFICANCE: THESE FINDINGS SHOW THAT: 1)
      HIPK2 knockdown induced COX-2 upregulation, mostly depending on HIF-1 activity;
      2) zinc treatment downregulated HIF-1-induced COX-2 and inhibited PGE(2)/VEGF
      production; and 3) zinc treatment of HIPK2 depleted cells restored DCs
      maturation.

PMID- 23144867
TI  - Cooperative anti-invasive effect of Cdc42/Rac1 activation and ROCK inhibition in
      SW620 colorectal cancer cells with elevated blebbing activity.
AB  - Rho GTPases are key regulators of tumour cell invasion and therefore constitute
      attractive targets for the design of anticancer agents. Several strategies have
      been developed to modulate their increased activities during cancer progression.
      Interestingly, none of these approaches took into account the existence of the
      well-known antagonistic relationship between RhoA and Rac1. In this study, we
      first compared the invasiveness of a collection of colorectal cancer cell lines
      with their RhoA, Rac1 and Cdc42 activities. A marked decrease of active Cdc42 and
      Rac1 correlated with the high invasive potential of the cell lines established
      from metastatic sites of colorectal adenocarcinoma (LoVo, SKCo1, SW620 and
      CoLo205). Conversely, no correlation between RhoA activity and invasiveness was
      detected, whereas the activity of its kinase effector ROCK was higher in cancer
      cell lines with a more invasive phenotype. In addition, invasiveness in these
      colon cancer cell lines was correlated with a typical round and blebbing
      morphology. We then tested whether treatment with PDGF to restore Cdc42 and Rac1
      activities and/or with Y27632, a chemical inhibitor of ROCK, could decrease the
      invasiveness of SW620 cells. The association of both treatments substantially
      decreased the invasive potential of SW620 cells and this effect was accompanied
      by loss of membrane blebbing, restoration of a more elongated cell morphology and
      re-establishment of E-cadherin-dependent adherens junctions. This study paves the
      road to the development of therapeutic strategies in which different Rho GTPase
      modulators are combined to modulate the cross-talk between Rho GTPases and their
      specific input in metastatic progression.

PMID- 23144868
TI  - Tubulointerstitial de novo expression of the alpha8 integrin chain in a rodent
      model of renal fibrosis--a potential target for anti-fibrotic therapy?
AB  - In the normal kidney, the alpha8 integrin chain is expressed only on mesangial
      cells and vascular smooth muscle cells. alpha8 integrin ligates several matrix
      molecules including fibronectin, osteopontin and fibrillin-1. Recently, we
      detected de novo expression of alpha8 integrin on epithelial cells in renal
      cysts. We hypothesized that the alpha8 integrin chain is induced in tubular
      epithelia undergoing dedifferentiation and contributes to the fibrotic response
      in the tubulointerstitium (TI) after unilateral ureteral obstruction (UUO). After
      induction of UUO in rats by ligation of the right ureter, increased expression of
      the alpha8 integrin chain and its ligands was observed. In the TI, alpha8
      integrin was localized to cytokeratin-positive epithelial cells and to
      interstitial fibroblasts; and colocalized with its ligands. In mice
      underexpressing alpha8 integrin UUO led to collagen deposition and fibroblast
      activation comparable to wild types. Mice lacking alpha8 integrin showed even
      more TI damage, fibroblast activation and collagen deposition after UUO compared
      to wild type mice. We conclude that the expression of the alpha8 integrin chain
      and its ligands is strongly induced in the TI after UUO, but underexpression of
      alpha8 integrin does not attenuate TI fibrosis. Mice lacking the alpha8 integrin
      chain are even more susceptible to TI damage than wild type mice. Thus,
      interactions of alpha8 integrin with its ligands do not seem to contribute to the
      development or progression of TI fibrosis in UUO. Targeting alpha8 integrin might
      not be a useful approach for anti-fibrotic therapy.

PMID- 23144869
TI  - Next-generation sequencing for rodent barcoding: species identification from
      fresh, degraded and environmental samples.
AB  - Rodentia is the most diverse order among mammals, with more than 2,000 species
      currently described. Most of the time, species assignation is so difficult based
      on morphological data solely that identifying rodents at the specific level
      corresponds to a real challenge. In this study, we compared the applicability of
      100 bp mini-barcodes from cytochrome b and cytochrome c oxidase 1 genes to enable
      rodent species identification. Based on GenBank sequence datasets of 115 rodent
      species, a 136 bp fragment of cytochrome b was selected as the most
      discriminatory mini-barcode, and rodent universal primers surrounding this
      fragment were designed. The efficacy of this new molecular tool was assessed on
      946 samples including rodent tissues, feces, museum samples and feces/pellets
      from predators known to ingest rodents. Utilizing next-generation sequencing
      technologies able to sequence mixes of DNA, 1,140 amplicons were tagged,
      multiplexed and sequenced together in one single 454 GS-FLX run. Our method was
      initially validated on a reference sample set including 265 clearly identified
      rodent tissues, corresponding to 103 different species. Following validation,
      85.6% of 555 rodent samples from Europe, Asia and Africa whose species identity
      was unknown were able to be identified using the BLASTN program and GenBank
      reference sequences. In addition, our method proved effective even on degraded
      rodent DNA samples: 91.8% and 75.9% of samples from feces and museum specimens
      respectively were correctly identified. Finally, we succeeded in determining the
      diet of 66.7% of the investigated carnivores from their feces and 81.8% of owls
      from their pellets. Non-rodent species were also identified, suggesting that our
      method is sensitive enough to investigate complete predator diets. This study
      demonstrates how this molecular identification method combined with high
      throughput sequencing can open new realms of possibilities in achieving fast,
      accurate and inexpensive species identification.

PMID- 23144870
TI  - A microscale model for combined CO(2) diffusion and photosynthesis in leaves.
AB  - Transport of CO(2) in leaves was investigated by combining a 2-D, microscale
      CO(2) transport model with photosynthesis kinetics in wheat (Triticum aestivum
      L.) leaves. The biophysical microscale model for gas exchange featured an
      accurate geometric representation of the actual 2-D leaf tissue microstructure
      and accounted for diffusive mass exchange of CO(2.) The resulting gas transport
      equations were coupled to the biochemical Farquhar-von Caemmerer-Berry model for
      photosynthesis. The combined model was evaluated using gas exchange and
      chlorophyll fluorescence measurements on wheat leaves. In general a good
      agreement between model predictions and measurements was obtained, but a
      discrepancy was observed for the mesophyll conductance at high CO(2) levels and
      low irradiance levels. This may indicate that some physiological processes
      related to photosynthesis are not incorporated in the model. The model provided
      detailed insight into the mechanisms of gas exchange and the effects of changes
      in ambient CO(2) concentration or photon flux density on stomatal and mesophyll
      conductance. It represents an important step forward to study CO(2) diffusion
      coupled to photosynthesis at the leaf tissue level, taking into account the
      leaf's actual microstructure.

PMID- 23144871
TI  - Fluorescence behavioral imaging (FBI) tracks identity in heterogeneous groups of
      Drosophila.
AB  - Distinguishing subpopulations in group behavioral experiments can reveal the
      impact of differences in genetic, pharmacological and life-histories on social
      interactions and decision-making. Here we describe Fluorescence Behavioral
      Imaging (FBI), a toolkit that uses transgenic fluorescence to discriminate
      subpopulations, imaging hardware that simultaneously records behavior and
      fluorescence expression, and open-source software for automated, high-accuracy
      determination of genetic identity. Using FBI, we measure courtship partner choice
      in genetically mixed groups of Drosophila.

PMID- 23144872
TI  - Predicting turns in proteins with a unified model.
AB  - MOTIVATION: Turns are a critical element of the structure of a protein; turns
      play a crucial role in loops, folds, and interactions. Current prediction methods
      are well developed for the prediction of individual turn types, including alpha
      turn, beta-turn, and gamma-turn, etc. However, for further protein structure and
      function prediction it is necessary to develop a uniform model that can
      accurately predict all types of turns simultaneously. RESULTS: In this study, we
      present a novel approach, TurnP, which offers the ability to investigate all the
      turns in a protein based on a unified model. The main characteristics of TurnP
      are: (i) using newly exploited features of structural evolution information
      (secondary structure and shape string of protein) based on structure homologies,
      (ii) considering all types of turns in a unified model, and (iii) practical
      capability of accurate prediction of all turns simultaneously for a query. TurnP
      utilizes predicted secondary structures and predicted shape strings, both of
      which have greater accuracy, based on innovative technologies which were both
      developed by our group. Then, sequence and structural evolution features, which
      are profile of sequence, profile of secondary structures and profile of shape
      strings are generated by sequence and structure alignment. When TurnP was
      validated on a non-redundant dataset (4,107 entries) by five-fold cross
      validation, we achieved an accuracy of 88.8% and a sensitivity of 71.8%, which
      exceeded the most state-of-the-art predictors of certain type of turn. Newly
      determined sequences, the EVA and CASP9 datasets were used as independent tests
      and the results we achieved were outstanding for turn predictions and confirmed
      the good performance of TurnP for practical applications.

PMID- 23144873
TI  - Molecular evidence for the thriving of Campylobacter jejuni ST-4526 in Japan.
AB  - Campylobacter jejuni is a leading cause of human gastroenteritis worldwide. This
      study aimed at a better understanding of the genetic diversity of this pathogen
      disseminated in Japan. We performed multilocus sequence typing (MLST) of
      Campylobacter jejuni isolated from different sources (100 human, 61 poultry, and
      51 cattle isolates) in Japan between 2005 and 2006. This approach identified 62
      sequence types (STs) and 19 clonal complexes (CCs), including 11 novel STs. These
      62 STs were phylogenetically divided into 6 clusters, partially exhibiting host
      association. We identified a novel ST (ST-4526) that has never been reported in
      other countries; a phylogenetic analysis showed that ST-4526 and related STs
      showed distant lineage from the founder ST, ST-21 within CC-21. Comparative
      genome analysis was performed to investigate which properties could be
      responsible for the successful dissemination of ST-4526 in Japan. Results
      revealed that three representative ST-4526 isolates contained a putative island
      comprising the region from Cj0737 to Cj0744, which differed between the ST-4526
      isolates and the reference strain NCTC11168 (ST-43/CC-21). Amino acid sequence
      alignment analyses showed that two of three ST-4526 isolates expressed 693aa-
      filamentous hemagglutination domain protein (FHA), while most of other C. jejuni
      strains whose genome were sequenced exhibited its truncation. Correspondingly,
      host cell binding of FHA-positive C. jejuni was greater than that of FHA
      truncated strains, and exogenous administration of rFHA protein reduced cell
      adhesion of FHA-positive bacteria. Biochemical assays showed that this putative
      protein exhibited a dose-dependent binding affinity to heparan sulfate,
      indicating its adhesin activity. Moreover, ST-4526 showed increased antibiotic
      resistance (nalidixic acid and fluoroquinolones) and a reduced ability for DNA
      uptake. Taken together, our data suggested that these combined features
      contributed to the clonal thriving of ST-4526 in Japan.

PMID- 23144874
TI  - DNA hypomethylation affects cancer-related biological functions and genes
      relevant in neuroblastoma pathogenesis.
AB  - Neuroblastoma (NB) pathogenesis has been reported to be closely associated with
      numerous genetic alterations. However, underlying DNA methylation patterns have
      not been extensively studied in this developmental malignancy. Here, we generated
      microarray-based DNA methylation profiles of primary neuroblastic tumors.
      Stringent supervised differential methylation analyses allowed us to identify
      epigenetic changes characteristic for NB tumors as well as for clinical and
      biological subtypes of NB. We observed that gene-specific loss of DNA methylation
      is more prevalent than promoter hypermethylation. Remarkably, such
      hypomethylation affected cancer-related biological functions and genes relevant
      to NB pathogenesis such as CCND1, SPRR3, BTC, EGF and FGF6. In particular,
      differential methylation in CCND1 affected mostly an evolutionary conserved
      functionally relevant 3' untranslated region, suggesting that hypomethylation
      outside promoter regions may play a role in NB pathogenesis. Hypermethylation
      targeted genes involved in cell development and proliferation such as RASSF1A,
      POU2F2 or HOXD3, among others. The results derived from this study provide new
      candidate epigenetic biomarkers associated with NB as well as insights into the
      molecular pathogenesis of this tumor, which involves a marked gene-specific
      hypomethylation.

PMID- 23144875
TI  - Indocyanine green-assisted internal limiting membrane peeling in macular hole
      surgery: a meta-analysis.
AB  - BACKGROUND: The opinion of application of indocyanine green (ICG) in the macular
      hole surgery was contradictory. Here we conducted a meta-analysis to evaluate the
      effect of in internal limiting membrane (ILM) peeling for macular hole surgery.
      METHODS AND FINDINGS: We searched electronic databases for comparative studies
      published before July 2012 of ILM peeling with and without ICG. Twenty-two
      studies including 1585 eyes were included. Visual acuity (VA) improvement,
      including the postoperative rate of >=20/40 VA gained (OR, 0.65; 95% CI, 0.43 to
      0.97; P = 0.033) and increased LogMAR (WMD, -0.09; 95% CI, -0.16 to -0.02; P =
      0.011), was less in the ICG group. The risk of visual field defects was greater
      in the ICG group than in the non-ICG group. There was no significant difference
      in the rate of anatomical outcomes between ILM peeling procedures performed with
      and without ICG. RPE changes and other postoperative complications were not
      significantly different between the ICG and non-ICG groups. An additional
      analysis showed that the VA improvement of the ICG group was less than the non
      ICG group only within the first year of follow up. A subgroup analysis showed
      that the rate of VA improvement was lower in the ICG group than in other adjuncts
      group. A higher rate of secondary closure and less VA improvement were observed
      in a high proportion (>0.1%) of the ICG group. A sensitivity analysis after the
      randomized-controlled trials were excluded from the meta-analysis demonstrated no
      differences compared with the overall results. CONCLUSIONS: This meta-analysis
      demonstrated that there is no evidence of clinical superiority in outcomes for
      ICG-assisted ILM peeling procedure over the non-ICG one. The toxicity of ICG
      should be considered when choosing the various staining methods.

PMID- 23144876
TI  - Enterovirus RNA in peripheral blood may be associated with the variants of
      rs1990760, a common type 1 diabetes associated polymorphism in IFIH1.
AB  - OBJECTIVE: Polymorphisms in the IFIH1 (common rs1990760 and four rare rs35667974,
      rs35337543, rs35744605, rs35732034) have been convincingly associated with type 1
      diabetes. The encoded protein (interferon-induced helicase C domain-containing
      protein 1) senses double-stranded RNA during replication of Picornavirales,
      including Enterovirus, a genus suspected in the etiology of type 1 diabetes. We
      therefore investigated whether the polymorphisms are associated with differences
      in the frequency of enterovirus RNA in blood. RESEARCH DESIGN AND METHODS: The
      study included 1001 blood samples, each from a child participating in the
      Norwegian 'Environmental Triggers of Type 1 Diabetes: the MIDIA study'. The
      enterovirus RNA was tested using qualitative semi-nested real-time reverse
      transcriptase PCR on RNA extracted from frozen cell packs after removal of
      plasma. Stool samples previously analyzed for enterovirus RNA were available in
      417 children. RESULTS: The genotypes of IFIH1 rs1990760 were associated with
      different frequencies of enterovirus RNA in blood (7.0%, 14.4% and 9.5% bloods
      were enterovirus positive among children carrying the Ala/Ala, Ala/Thr and
      Thr/Thr genotypes, respectively, p = 0.012). This association remained
      essentially unchanged after adjustment for age and calendar year. The presence of
      enterovirus in the concomitantly sampled stool further increased the likelihood
      of enterovirus RNA in blood (odds ratio 2.40, CI 95% 1.13-4.70), but did not
      affect the association with IFIH1 rs1990760. The rare polymorphisms
      (individually, or pooled) were not significantly associated with enterovirus RNA
      in blood. CONCLUSIONS: The common IFIH1 SNP may modify the frequency of
      enterovirus RNA in blood of healthy children. This effect can help explain the
      association of IFIH1 with type 1 diabetes.

PMID- 23144877
TI  - A non-synonymous single nucleotide polymorphism in an OPRM1 splice variant is
      associated with fentanyl-induced emesis in women undergoing minor gynaecological
      surgery.
AB  - BACKGROUND: Fentanyl-induced emesis (FIE) is a distressing adverse effect in the
      postoperative setting. The genetic basis of FIE remains largely unknown,
      therefore, we examined whether it was associated with specific genetic variants
      of OPRM1, the gene encoding the main receptor target of fentanyl. METHODS: In
      this prospective case-control study, 193 women undergoing gynaecological surgery
      under a standardized anaesthetic with a low emetogenic risk were enrolled.
      Inclusion and exclusion criteria were designed to select extreme phenotypes as
      well as to ensure that most major confounders for FIE were either excluded or
      present in all patients. To control for unforeseen intra- and postoperative
      confounders for FIE, only 161 patients were further analysed, out of which 10
      were categorized as having FIE, defined by the presence of at least one of three
      symptoms: nausea, vomiting or retching that was likely to be fentanyl-related. To
      identify SNPs relevant to FIE in our population, DNA from 40 controls and 10
      cases was sequenced at the following OPRM1 regions: 3 kbp of the promoter, main
      and alternative exons as well as 2 kbp of the 3' downstream region. The genotype
      of the significant SNP was further determined in the remaining 111 controls.
      RESULTS: The incidence of FIE was 6.2%. Initial sequencing of 10 cases and 40
      controls identified 25 SNPs. Only rs540825, a non-synonymous SNP in the splice
      variant, MOR1X, showed a significant association with FIE post-Bonferroni
      correction. This SNP was further examined in the remaining 111 controls which
      confirmed its significant association with FIE (p = 0.019 post-Bonferroni, OR:
      5.6, 95% CI: 1.42-21.91). CONCLUSIONS: This is the first report of an association
      between the occurrence of FIE in Chinese women undergoing gynaecological surgery
      and an OPRM1 splice variant SNP, rs540825.

PMID- 23144879
TI  - Potential benefits of second-generation human papillomavirus vaccines.
AB  - BACKGROUND: Current prophylactic vaccines against human papillomavirus (HPV)
      target two oncogenic types (16 and 18) that contribute to 70% of cervical cancer
      cases worldwide. Our objective was to quantify the range of additional benefits
      conferred by second-generation HPV prophylactic vaccines that are expected to
      expand protection to five additional oncogenic types (31, 33, 45, 52 and 58).
      METHODS: A microsimulation model of HPV and cervical cancer calibrated to
      epidemiological data from two countries (Kenya and Uganda) was used to estimate
      reductions in lifetime risk of cervical cancer from the second-generation HPV
      vaccines. We explored the independent and joint impact of uncertain factors
      (i.e., distribution of HPV types, co-infection with multiple HPV types, and
      unidentifiable HPV types in cancer) and vaccine properties (i.e., cross
      protection against non-targeted HPV types), compared against currently-available
      vaccines. RESULTS: Assuming complete uptake of the second-generation vaccine,
      reductions in lifetime cancer risk were 86.3% in Kenya and 91.8% in Uganda,
      representing an absolute increase in cervical cancer reduction of 26.1% in Kenya
      and 17.9% in Uganda, compared with complete uptake of current vaccines. The range
      of added benefits was 19.6% to 29.1% in Kenya and 14.0% to 19.5% in Uganda,
      depending on assumptions of cancers attributable to multiple HPV infections and
      unidentifiable HPV types. These effects were blunted in both countries when
      assuming vaccine cross-protection with both the current and second-generation
      vaccines. CONCLUSION: Second-generation HPV vaccines that protect against
      additional oncogenic HPV types have the potential to improve cervical cancer
      prevention. Co-infection with multiple HPV infections and unidentifiable HPV
      types can influence vaccine effectiveness, but the magnitude of effect may be
      moderated by vaccine cross-protective effects. These benefits must be weighed
      against the cost of the vaccines in future analyses.

PMID- 23144878
TI  - Endobiont viruses sensed by the human host - beyond conventional antiparasitic
      therapy.
AB  - Wide-spread protozoan parasites carry endosymbiotic dsRNA viruses with uncharted
      implications to the human host. Among them, Trichomonas vaginalis, a parasite
      adapted to the human genitourinary tract, infects globally ~250 million each year
      rendering them more susceptible to devastating pregnancy complications
      (especially preterm birth), HIV infection and HPV-related cancer. While first
      line antibiotic treatment (metronidazole) commonly kills the protozoan pathogen,
      it fails to improve reproductive outcome. We show that endosymbiotic
      Trichomonasvirus, highly prevalent in T. vaginalis clinical isolates, is sensed
      by the human epithelial cells via Toll-like receptor 3, triggering Interferon
      Regulating Factor -3, interferon type I and proinflammatory cascades previously
      implicated in preterm birth and HIV-1 susceptibility. Metronidazole treatment
      amplified these proinflammatory responses. Thus, a new paradigm targeting the
      protozoan viruses along with the protozoan host may prevent trichomoniasis
      attributable inflammatory sequelae.

PMID- 23144880
TI  - Re-evaluate the effect of hyperbaric oxygen therapy in cancer - a preclinical
      therapeutic small animal model study.
AB  - Tumor hypoxia is a known driver of angiogenesis that also facilitates tumor
      growth. Moreover, poorly oxygenated central tumor area remains relatively radio
      or chemo resistant. HBO therapy is known to elevate the levels of dissolved
      oxygen and eliminates tumor hypoxia. It has been one of the modalities in cancer
      treatment; therefore its optimization is important. In this experimental study,
      no cancer enhancing effect was seen during the course of HBO therapy; however,
      post therapy there was an accelerated growth and progression of tumor. HBO
      treated mice lived shorter and the response to therapy was dose & tumor volume
      dependent. HBO therapy probably exert its effect on the cancer proliferating
      cells through multiple pathways such as increased DNA damage, apoptosis & geno
      toxicity leading to slow cancer progression while post therapy tumorigenic effect
      could be due to impaired DNA repair mechanism, mutagenic effect & aneuploidy as
      well as altered blood supply & nutrients. Tumor growth reached plateau with time
      and this finding validated theoretical model predicting tumor reaching an
      asymptotic limit. While, marked asymmetry observed in tumor volume progression or
      cancer cell proliferation rate in each of the experimental C3H mouse suggested a
      need for an alternate small animal pre-clinical cancer therapeutic model.

PMID- 23144881
TI  - Is working more costly than waiting in monkeys?
AB  - We studied how value for instrumental action is discounted by predicted effort
      and delay. The monkeys were trained to perform instrumental trials that required
      a bar release when a visual target changed from red-to-green. There were two
      trial conditions. In delay trials, after the monkeys performed one instrumental
      trial correctly a reward was delivered 0-7 seconds later. In work trials, the
      monkeys had to perform 0, 1, or 2 additional instrumental trials to obtain a
      reward. The lengths of trials in delay matched the time it took to complete work
      trials. The length of delay or number of trials was indicated by a visual cue
      presented throughout the trial. Our hypothesis was that the monkeys would all
      show temporal discounting of reward in the delay trials, and that in the work
      trials the monkeys' performance might reflect an additional cost due to working.
      The error rate increased linearly as remaining cost increased for all 8 monkeys.
      For 4 monkeys the error rate was significantly larger in work trials than in
      delay trials (effort sensitive monkeys). For the other 4 monkeys there was no
      significant difference in error rate (effort insensitive monkeys). Since the
      error rate has an inverse relation with value for action, these results suggest
      that value is discounted hyperbolically by effort as well as by delay. Error
      rates generally increased as the testing sessions progressed and the total reward
      accumulated (i.e., effect of reward devaluation). The relative impact of delay
      and effort on error rates was reasonably stable within subjects. Thus, within the
      monkey population there seems to be a significant dichotomy in the sensitivity
      governing whether working is more costly than waiting, possibly arising from a
      constitutional or genetic trait.

PMID- 23144882
TI  - Quorum sensing and density-dependent dispersal in an aquatic model system.
AB  - Many organisms use cues to decide whether to disperse or not, especially those
      related to the composition of their environment. Dispersal hence sometimes
      depends on population density, which can be important for the dynamics and
      evolution of sub-divided populations. But very little is known about the factors
      that organisms use to inform their dispersal decision. We investigated the cues
      underlying density-dependent dispersal in inter-connected microcosms of the
      freshwater protozoan Paramecium caudatum. In two experiments, we manipulated (i)
      the number of cells per microcosm and (ii) the origin of their culture medium
      (supernatant from high- or low-density populations). We found a negative
      relationship between population density and rates of dispersal, suggesting the
      use of physical cues. There was no significant effect of culture medium origin on
      dispersal and thus no support for chemical cues usage. These results suggest that
      the perception of density - and as a result, the decision to disperse - in this
      organism can be based on physical factors. This type of quorum sensing may be an
      adaptation optimizing small scale monitoring of the environment and swarm
      formation in open water.

PMID- 23144883
TI  - Insight into the wild origin, migration and domestication history of the fine
      flavour Nacional Theobroma cacao L. variety from Ecuador.
AB  - Ecuador's economic history has been closely linked to Theobroma cacao L
      cultivation, and specifically to the native fine flavour Nacional cocoa variety.
      The original Nacional cocoa trees are presently in danger of extinction due to
      foreign germplasm introductions. In a previous work, a few non-introgressed
      Nacional types were identified as potential founders of the modern Ecuadorian
      cocoa population, but so far their origin could not be formally identified. In
      order to determine the putative centre of origin of Nacional and trace its
      domestication history, we used 80 simple sequence repeat (SSR) markers to analyse
      the relationships between these potential Nacional founders and 169 wild and
      cultivated cocoa accessions from South and Central America. The highest genetic
      similarity was observed between the Nacional pool and some wild genotypes from
      the southern Amazonian region of Ecuador, sampled along the Yacuambi, Nangaritza
      and Zamora rivers in Zamora Chinchipe province. This result was confirmed by a
      parentage analysis. Based on our results and on data about pre-Columbian
      civilization and Spanish colonization history of Ecuador, we determined, for the
      first time, the possible centre of origin and migration events of the Nacional
      variety from the Amazonian area until its arrival in the coastal provinces. As
      large unexplored forest areas still exist in the southern part of the Ecuadorian
      Amazonian region, our findings could provide clues as to where precious new
      genetic resources could be collected, and subsequently used to improve the
      flavour and disease resistance of modern Ecuadorian cocoa varieties.

PMID- 23144884
TI  - Impact of habitat-specific GPS positional error on detection of movement scales
      by first-passage time analysis.
AB  - Advances in animal tracking technologies have reduced but not eliminated
      positional error. While aware of such inherent error, scientists often proceed
      with analyses that assume exact locations. The results of such analyses then
      represent one realization in a distribution of possible outcomes. Evaluating
      results within the context of that distribution can strengthen or weaken our
      confidence in conclusions drawn from the analysis in question. We evaluated the
      habitat-specific positional error of stationary GPS collars placed under a range
      of vegetation conditions that produced a gradient of canopy cover. We explored
      how variation of positional error in different vegetation cover types affects a
      researcher's ability to discern scales of movement in analyses of first-passage
      time for white-tailed deer (Odocoileus virginianus). We placed 11 GPS collars in
      4 different vegetative canopy cover types classified as the proportion of cover
      above the collar (0-25%, 26-50%, 51-75%, and 76-100%). We simulated the effect of
      positional error on individual movement paths using cover-specific error
      distributions at each location. The different cover classes did not introduce any
      directional bias in positional observations (1 m<=mean<=6.51 m, 0.24<=p<=0.47),
      but the standard deviation of positional error of fixes increased significantly
      with increasing canopy cover class for the 0-25%, 26-50%, 51-75% classes (SD =
      2.18 m, 3.07 m, and 4.61 m, respectively) and then leveled off in the 76-100%
      cover class (SD = 4.43 m). We then added cover-specific positional errors to
      individual deer movement paths and conducted first-passage time analyses on the
      noisy and original paths. First-passage time analyses were robust to habitat
      specific error in a forest-agriculture landscape. For deer in a fragmented forest
      agriculture environment, and species that move across similar geographic extents,
      we suggest that first-passage time analysis is robust with regard to positional
      errors.

PMID- 23144885
TI  - Implicit and explicit anti-fat bias among a large sample of medical doctors by
      BMI, race/ethnicity and gender.
AB  - Overweight patients report weight discrimination in health care settings and
      subsequent avoidance of routine preventive health care. The purpose of this study
      was to examine implicit and explicit attitudes about weight among a large group
      of medical doctors (MDs) to determine the pervasiveness of negative attitudes
      about weight among MDs. Test-takers voluntarily accessed a public Web site, known
      as Project Implicit(r), and opted to complete the Weight Implicit Association
      Test (IAT) (N = 359,261). A sub-sample identified their highest level of
      education as MD (N = 2,284). Among the MDs, 55% were female, 78% reported their
      race as white, and 62% had a normal range BMI. This large sample of test-takers
      showed strong implicit anti-fat bias (Cohen's d = 1.0). MDs, on average, also
      showed strong implicit anti-fat bias (Cohen's d = 0.93). All test-takers and the
      MD sub-sample reported a strong preference for thin people rather than fat people
      or a strong explicit anti-fat bias. We conclude that strong implicit and explicit
      anti-fat bias is as pervasive among MDs as it is among the general public. An
      important area for future research is to investigate the association between
      providers' implicit and explicit attitudes about weight, patient reports of
      weight discrimination in health care, and quality of care delivered to overweight
      patients.

PMID- 23144886
TI  - Time trends in population prevalence of eating disorder behaviors and their
      relationship to quality of life.
AB  - OBJECTIVE: To examine temporal trends in the burden of eating disorder (ED)
      features, as estimated by the composite of their prevalence and impact upon
      quality of life (QoL) over a period of 10 years. METHODOLOGY: Representative
      samples of 3010 participants in 1998 and 3034 participants in 2008 from the South
      Australian adult population were assessed for endorsement of ED features
      (objective binge eating, extreme dieting, and purging were assessed in both
      years; subjective binge eating and extreme weight/shape concerns were also
      assessed in 2008) and QoL using the Medical Outcomes Study Short Form (SF-36).
      PRINCIPAL FINDINGS: From 1998 to 2008 significant increases in the prevalence of
      objective binge eating (2.7% to 4.9%, p<0.01) and extreme dieting (1.5% to 3.3%,
      p<0.01), but not purging, were observed. Lower scores on the SF-36 were
      significantly associated with endorsement of any of these behaviors in both 1998
      and 2008 (all p<0.001). No significant difference was observed in the effect of
      the endorsement of these ED behaviors on QoL between 1998 and 2008 (all p>0.05).
      Multiple linear regressions found that in 1998 only objective binge eating
      significantly predicted scores on the mental health summary scale of the SF-36;
      however, in 2008 extreme weight/shape concerns, extreme dieting, and subjective
      binge eating were also significant predictors. Objective binge eating and extreme
      dieting were significant predictors of scores on the physical health summary
      scale of the SF-36 in both 1998 and 2008. CONCLUSIONS AND SIGNIFICANCE: The
      prevalence of ED behaviors increased between 1998 and 2008, while their impact on
      QoL remained stable. This suggests an overall increase in the burden of
      disordered eating from 1998 to 2008. Given that binge eating and extreme dieting
      predict impairment in QoL, the necessity of interventions to prevent both under-
      and over-eating is reinforced.

PMID- 23144887
TI  - Coarse-grained prediction of RNA loop structures.
AB  - One of the key issues in the theoretical prediction of RNA folding is the
      prediction of loop structure from the sequence. RNA loop free energies are
      dependent on the loop sequence content. However, most current models account only
      for the loop length-dependence. The previously developed "Vfold" model (a coarse
      grained RNA folding model) provides an effective method to generate the complete
      ensemble of coarse-grained RNA loop and junction conformations. However, due to
      the lack of sequence-dependent scoring parameters, the method is unable to
      identify the native and near-native structures from the sequence. In this study,
      using a previously developed iterative method for extracting the knowledge-based
      potential parameters from the known structures, we derive a set of dinucleotide
      based statistical potentials for RNA loops and junctions. A unique advantage of
      the approach is its ability to go beyond the the (known) native structures by
      accounting for the full free energy landscape, including all the nonnative folds.
      The benchmark tests indicate that for given loop/junction sequences, the
      statistical potentials enable successful predictions for the coarse-grained 3D
      structures from the complete conformational ensemble generated by the Vfold
      model. The predicted coarse-grained structures can provide useful initial folds
      for further detailed structural refinement.

PMID- 23144888
TI  - Prime-boost vaccination with SA-4-1BBL costimulatory molecule and survivin
      eradicates lung carcinoma in CD8+ T and NK cell dependent manner.
AB  - Subunit vaccines containing universal tumor associated antigens (TAAs) present an
      attractive treatment modality for cancer primarily due to their safety and
      potential to generate long-term immunological responses that can safeguard
      against recurrences. However, TAA-based subunit vaccines require potent adjuvants
      for therapeutic efficacy. Using a novel form of the 4-1BBL costimulatory
      molecule, SA-4-1BBL, as the adjuvant of choice, we previously demonstrated that a
      single vaccination with survivin (SVN) as a bona fide self TAA was effective in
      eradicating weakly immunogenic 3LL tumors in >70% of C57BL/6 mice. The present
      study was designed to i) assess the therapeutic efficacy of a prime-boost
      vaccination and ii) investigate the mechanistic basis of vaccine efficacy. Our
      data shows that a prime-boost vaccination strategy was effective in eradicating
      3LL lung carcinoma in 100% of mice. The vaccine efficacy was correlated with
      increased percentages of CD8(+) T cells expressing IFN-gamma as well as potent
      killing responses of both CD8(+) T and NK cells in the absence of detectable
      antibodies to ssDNA as a sign of autoimmunity. Antibody depletion of CD8(+) T
      cells one day before vaccination completely abrogated therapeutic efficacy,
      whereas depletion of CD4(+) T cells had no effect. Importantly, NK cell depletion
      had a moderate (~50% reduction), but significant (p<0.05) effect on vaccine
      efficacy. Taken together, these results shed light on the mechanistic basis of
      the SA-4-1BBL/SVN subunit vaccine formulation in a lung carcinoma model and
      demonstrate the robust therapeutic efficacy of the prime-boost immunization
      strategy with important clinical implications.

PMID- 23144889
TI  - Anti-inflammatory activity of a novel family of aryl ureas compounds in an
      endotoxin-induced airway epithelial cell injury model.
AB  - BACKGROUND: Despite our increased understanding of the mechanisms involved in
      acute lung injury (ALI) and the acute respiratory distress syndrome (ARDS), there
      is no specific pharmacological treatment of proven benefit. We used a novel
      screening methodology to examine potential anti-inflammatory effects of a small
      structure-focused library of synthetic carbamate and urea derivatives in a well
      established cell model of lipopolysaccharide (LPS)-induced ALI/ARDS.
      METHODOLOGY/PRINCIPAL FINDINGS: After a pilot study to develop an in vitro LPS
      induced airway epithelial cell injury model, a library of synthetic carbamate and
      urea derivates was screened against representative panels of human solid tumor
      cell lines and bacterial and fungal strains. Molecules that were non-cytotoxic
      and were inactive in terms of antiproliferative and antimicrobial activities were
      selected to study the effects on LPS-induced inflammatory response in an in vitro
      cell culture model using A549 human alveolar and BEAS-2B human bronchial cells.
      These cells were exposed for 18 h to LPS obtained from Escherichia coli, either
      alone or in combination with the test compounds. The LPS antagonists rhein and
      emodin were used as reference compounds. The most active compound (CKT0103) was
      selected as the lead compound and the impact of CKT0103 on pro-inflammatory IL-6
      and IL-8 cytokine levels, expression of toll-like receptor-4 (TLR4) and nuclear
      factor kappa B inhibitor alpha (IkappaBalpha) was measured. CKT0103 significantly
      inhibited the synthesis and release of IL-6 and IL-8 induced by LPS. This
      suppression was associated with inhibition of TLR4 up-regulation and IkappaBalpha
      down-regulation. Immunocytochemical staining for TLR4 and IkappaBalpha supported
      these findings. CONCLUSIONS/SIGNIFICANCE: Using a novel screening methodology, we
      identified a compound - CKT0103 - with potent anti-inflammatory effects. These
      findings suggest that CKT0103 is a potential target for the treatment of the
      acute phase of sepsis and sepsis-induced ALI/ARDS.

PMID- 23144890
TI  - Neurons of the dentate molecular layer in the rabbit hippocampus.
AB  - The molecular layer of the dentate gyrus appears as the main entrance gate for
      information into the hippocampus, i.e., where the perforant path axons from the
      entorhinal cortex synapse onto the spines and dendrites of granule cells. A few
      dispersed neuronal somata appear intermingled in between and probably control the
      flow of information in this area. In rabbits, the number of neurons in the
      molecular layer increases in the first week of postnatal life and then stabilizes
      to appear permanent and heterogeneous over the individuals' life span, including
      old animals. By means of Golgi impregnations, NADPH histochemistry,
      immunocytochemical stainings and intracellular labelings (lucifer yellow and
      biocytin injections), eight neuronal morphological types have been detected in
      the molecular layer of developing adult and old rabbits. Six of them appear as
      interneurons displaying smooth dendrites and GABA immunoreactivity: those here
      called as globoid, vertical, small horizontal, large horizontal, inverted
      pyramidal and polymorphic. Additionally there are two GABA negative types: the
      sarmentous and ectopic granular neurons. The distribution of the somata and
      dendritic trees of these neurons shows preferences for a definite sublayer of the
      molecular layer: small horizontal, sarmentous and inverted pyramidal neurons are
      preferably found in the outer third of the molecular layer; vertical, globoid and
      polymorph neurons locate the intermediate third, while large horizontal and
      ectopic granular neurons occupy the inner third or the juxtagranular molecular
      layer. Our results reveal substantial differences in the morphology and
      electrophysiological behaviour between each neuronal archetype in the dentate
      molecular layer, allowing us to propose a new classification for this neural
      population.

PMID- 23144891
TI  - A systematic screen reveals MicroRNA clusters that significantly regulate four
      major signaling pathways.
AB  - MicroRNAs (miRNAs) are encoded in the genome as individual miRNA genes or as gene
      clusters transcribed as polycistronic units. About 50% of all miRNAs are
      estimated to be co-expressed with neighboring miRNAs. Recent studies have begun
      to illuminate the importance of the clustering of miRNAs from an evolutionary, as
      well as a functional standpoint. Many miRNA clusters coordinately regulate
      multiple members of cellular signaling pathways or protein interaction networks.
      This cooperative method of targeting could produce effects on an overall process
      that are much more dramatic than the smaller effects often associated with
      regulation by an individual miRNA. In this study, we screened 366 human miRNA
      minigenes to determine their effects on the major signaling pathways culminating
      in AP-1, NF-kappaB, c-Myc, or p53 transcriptional activity. By stratifying these
      data into miRNA clusters, this systematic screen provides experimental evidence
      for the combined effects of clustered miRNAs on these signaling pathways. We also
      verify p53 as a direct target of miR-200a. This study is the first to provide a
      panoramic view of miRNA clusters' effects on cellular pathways.

PMID- 23144892
TI  - MHC class I-presented T cell epitopes identified by immunoproteomics analysis are
      targets for a cross reactive influenza-specific T cell response.
AB  - Influenza virus infection and the resulting complications are a significant
      global public health problem. Improving humoral immunity to influenza is the
      target of current conventional influenza vaccines, however, these are generally
      not cross-protective. On the contrary, cell-mediated immunity generated by
      primary influenza infection provides substantial protection against serologically
      distinct viruses due to recognition of cross-reactive T cell epitopes, often from
      internal viral proteins conserved between viral subtypes. Efforts are underway to
      develop a universal flu vaccine that would stimulate both the humoral and
      cellular immune responses leading to long-lived memory. Such a universal vaccine
      should target conserved influenza virus antibody and T cell epitopes that do not
      vary from strain to strain. In the last decade, immunoproteomics, or the direct
      identification of HLA class I presented epitopes, has emerged as an alternative
      to the motif prediction method for the identification of T cell epitopes. In this
      study, we used this method to uncover several cross-specific MHC class I specific
      T cell epitopes naturally presented by influenza A-infected cells. These
      conserved T cell epitopes, when combined with a cross-reactive antibody epitope
      from the ectodomain of influenza M2, generate cross-strain specific cell mediated
      and humoral immunity. Overall, we have demonstrated that conserved epitope
      specific CTLs could recognize multiple influenza strain infected target cells
      and, when combined with a universal antibody epitope, could generate virus
      specific humoral and T cell responses, a step toward a universal vaccine concept.
      These epitopes also have potential as new tools to characterize T cell immunity
      in influenza infection, and may serve as part of a universal vaccine candidate
      complementary to current vaccines.

PMID- 23144893
TI  - Caffeine improves left hemisphere processing of positive words.
AB  - A positivity advantage is known in emotional word recognition in that positive
      words are consistently processed faster and with fewer errors compared to
      emotionally neutral words. A similar advantage is not evident for negative words.
      Results of divided visual field studies, where stimuli are presented in either
      the left or right visual field and are initially processed by the contra-lateral
      brain hemisphere, point to a specificity of the language-dominant left
      hemisphere. The present study examined this effect by showing that the intake of
      caffeine further enhanced the recognition performance of positive, but not
      negative or neutral stimuli compared to a placebo control group. Because this
      effect was only present in the right visual field/left hemisphere condition, and
      based on the close link between caffeine intake and dopaminergic transmission,
      this result points to a dopaminergic explanation of the positivity advantage in
      emotional word recognition.

PMID- 23144894
TI  - Functional and structural properties of dentate granule cells with hilar basal
      dendrites in mouse entorhino-hippocampal slice cultures.
AB  - During postnatal development hippocampal dentate granule cells (GCs) often extend
      dendrites from the basal pole of their cell bodies into the hilar region. These
      so-called hilar basal dendrites (hBD) usually regress with maturation. However,
      hBDs may persist in a subset of mature GCs under certain conditions (both
      physiological and pathological). The functional role of these hBD-GCs remains not
      well understood. Here, we have studied hBD-GCs in mature (>=18 days in vitro)
      mouse entorhino-hippocampal slice cultures under control conditions and have
      compared their basic functional properties (basic intrinsic and synaptic
      properties) and structural properties (dendritic arborisation and spine
      densities) to those of neighboring GCs without hBDs in the same set of cultures.
      Except for the presence of hBDs, we did not detect major differences between the
      two GC populations. Furthermore, paired recordings of neighboring GCs with and
      without hBDs did not reveal evidence for a heavy aberrant GC-to-GC connectivity.
      Taken together, our data suggest that in control cultures the presence of hBDs on
      GCs is neither sufficient to predict alterations in the basic functional and
      structural properties of these GCs nor indicative of a heavy GC-to-GC
      connectivity between neighboring GCs.

PMID- 23144895
TI  - Liquid chromatography-tandem mass spectrometry for analysis of intestinal
      permeability of loperamide in physiological buffer.
AB  - Analysis of in vitro samples with high salt concentrations represents a major
      challenge for fast and specific quantification with liquid chromatography-tandem
      mass spectrometry (LC-MS/MS). To investigate the intestinal permeability of
      opioids in vitro employing the Ussing chamber technique, we developed and
      validated a fast, sensitive and selective method based on LC-MS/MS for the
      determination of loperamide in HEPES-buffered Ringer's solution. Chromatographic
      separation was achieved with an Atlantis dC18 column, 2.1 mm*20 mm, 3 um particle
      size and a gradient consisting of methanol/0.1% formic acid and ammonium acetate.
      The flow rate was 0.7 ml/min, and the total run time was 3 min. For
      quantification, two mass transitions for loperamide and a deuterated internal
      standard (methadone-d(3)) were used. The lower limit of loperamide quantification
      was 0.2 ng/ml. This new LC-MS/MS method can be used for the detection of
      loperamide in any experimental setup using HEPES-buffered Ringer's solution as a
      matrix compound.

PMID- 23144897
TI  - Division of labor regulates precision rescue behavior in sand-dwelling
      Cataglyphis cursor ants: to give is to receive.
AB  - Division of labor, an adaptation in which individuals specialize in performing
      tasks necessary to the colony, such as nest defense and foraging, is believed key
      to eusocial insects' remarkable ecological success. Here we report, for the first
      time, a completely novel specialization in a eusocial insect, namely the ability
      of Cataglyphis cursor ants to rescue a trapped nestmate using precisely targeted
      behavior. Labeled "precision rescue", this behavior involves the ability of
      rescuers not only to detect what, exactly, holds the victim in place, but also to
      direct specific actions to this obstacle. Individual ants, sampled from each of
      C. cursor's three castes, namely foragers, nurses and inactives, were
      experimentally ensnared (the "victim") and exposed to a caste-specific group of
      potential "rescuers." The data reveal that foragers were able to administer, and
      obtain, the most help while members of the youngest, inactive caste not only
      failed to respond to victims, but also received virtually no help from potential
      rescuers, regardless of caste. Nurses performed intermediate levels of aid,
      mirroring their intermediate caste status. Our results demonstrate that division
      of labor, which controls foraging, defense and brood care in C. cursor, also
      regulates a newly discovered behavior in this species, namely a sophisticated
      form of rescue, a highly adaptive specialization that is finely tuned to a caste
      member's probability of becoming, or encountering, a victim in need of rescue.

PMID- 23144896
TI  - Role of PKC and CaV1.2 in detrusor overactivity in a model of obesity associated
      with insulin resistance in mice.
AB  - Obesity/metabolic syndrome are common risk factors for overactive bladder. This
      study aimed to investigate the functional and molecular changes of detrusor
      smooth muscle (DSM) in high-fat insulin resistant obese mice, focusing on the
      role of protein kinase C (PKC) and Ca(v)1.2 in causing bladder dysfunction. Male
      C57BL/6 mice were fed with high-fat diet for 10 weeks. In vitro functional
      responses and cystometry, as well as PKC and Ca(v)1.2 expression in bladder were
      evaluated. Obese mice exhibited higher body weight, epididymal fat mass, fasting
      glucose and insulin resistance. Carbachol (0.001-100 uM), alpha,beta-methylene
      ATP (1-10 uM), KCl (1-300 mM), extracellular Ca(2+) (0.01-100 mM) and phorbol
      12,13-dibutyrate (PDBu; 0.001-3 uM) all produced greater DSM contractions in
      obese mice, which were fully reversed by the Ca(v)1.2 blocker amlodipine.
      Cystometry evidenced augmented frequency, non-void contractions and post-void
      pressure in obese mice that were also prevented by amlodipine. Metformin
      treatment improved the insulin sensitivity, and normalized the in vitro bladder
      hypercontractility and cystometric dysfunction in obese mice. The PKC inhibitor
      GF109203X (1 uM) also reduced the carbachol induced contractions. PKC protein
      expression was markedly higher in bladder tissues from obese mice, which was
      normalized by metformin treatment. The Ca(v)1.2 channel protein expression was
      not modified in any experimental group. Our findings show that Ca(v)1.2 blockade
      and improvement of insulin sensitization restores the enhanced PKC protein
      expression in bladder tissues and normalizes the overactive detrusor. It is
      likely that insulin resistance importantly contributes for the pathophysiology of
      this urological disorder in obese mice.

PMID- 23144898
TI  - An anatomical description of a miniaturized acorn worm (hemichordata,
      enteropneusta) with asexual reproduction by paratomy.
AB  - The interstitial environment of marine sandy bottoms is a nutrient-rich,
      sheltered habitat whilst at the same time also often a turbulent, space-limited,
      and ecologically challenging environment dominated by meiofauna. The interstitial
      fauna is one of the most diverse on earth and accommodates miniaturized
      representatives from many macrofaunal groups as well as several exclusively
      meiofaunal phyla. The colonization process of this environment, with the
      restrictions imposed by limited space and low Reynolds numbers, has selected for
      great morphological and behavioral changes as well as new life history
      strategies.Here we describe a new enteropneust species inhabiting the interstices
      among sand grains in shallow tropical waters of the West Atlantic. With a maximum
      body length of 0.6 mm, it is the first microscopic adult enteropneust known, a
      group otherwise ranging from 2 cm to 250 cm in adult size. Asexual reproduction
      by paratomy has been observed in this new species, a reproductive mode not
      previously reported among enteropneusts. Morphologically, Meioglossus
      psammophilus gen. et sp. nov. shows closest resemblance to an early juvenile
      stage of the acorn worm family Harrimaniidae, a result congruent with its
      phylogenetic placement based on molecular data. Its position, clearly nested
      within the larger macrofaunal hemichordates, suggests that this represents an
      extreme case of miniaturization. The evolutionary pathway to this simple or
      juvenile appearance, as chiefly demonstrated by its small size, dense ciliation,
      and single pair of gill pores, may be explained by progenesis. The finding of M.
      psammophilus gen. et sp. nov. underscores the notion that meiofauna may
      constitute a rich source of undiscovered metazoan diversity, possibly disguised
      as juveniles of other species.

PMID- 23144899
TI  - On ribosome load, codon bias and protein abundance.
AB  - Different codons encoding the same amino acid are not used equally in protein
      coding sequences. In bacteria, there is a bias towards codons with high
      translation rates. This bias is most pronounced in highly expressed proteins, but
      a recent study of synthetic GFP-coding sequences did not find a correlation
      between codon usage and GFP expression, suggesting that such correlation in
      natural sequences is not a simple property of translational mechanisms. Here, we
      investigate the effect of evolutionary forces on codon usage. The relation
      between codon bias and protein abundance is quantitatively analyzed based on the
      hypothesis that codon bias evolved to ensure the efficient usage of ribosomes, a
      precious commodity for fast growing cells. An explicit fitness landscape is
      formulated based on bacterial growth laws to relate protein abundance and
      ribosomal load. The model leads to a quantitative relation between codon bias and
      protein abundance, which accounts for a substantial part of the observed bias for
      E. coli. Moreover, by providing an evolutionary link, the ribosome load model
      resolves the apparent conflict between the observed relation of protein abundance
      and codon bias in natural sequences and the lack of such dependence in a
      synthetic gfp library. Finally, we show that the relation between codon usage and
      protein abundance can be used to predict protein abundance from genomic sequence
      data alone without adjustable parameters.

PMID- 23144900
TI  - Patient-reported experiences with first-time naturopathic care for type 2
      diabetes.
AB  - Differences in the effectiveness of diverse healthcare providers to promote
      health behavior change and successful diabetes self-care have received little
      attention. Because training in naturopathic medicine (NM) emphasizes a patient
      centered approach, health promotion, and routine use of clinical counseling on
      wellness and prevention, naturopathic physicians (NDs) may be particularly well
      prepared for promoting behavior change. However, patients' experiences with NM
      have not been well studied. This study provides the first report of the
      perceptions of persons with type 2 diabetes of their first experiences with
      naturopathic care for their diabetes. Following their participation in a one-year
      prospective cohort study of adjunctive naturopathic care for diabetes, twenty-two
      patients were interviewed about their experiences working with a naturopathic
      physician. Using a content analysis approach, nine dominant themes were
      identified. Three themes characterized the nature of the ND-patient interaction:
      1) patient-centered, 2) holistic health rather than diabetes focused, and 3)
      collaborative. Five themes characterized the content of the clinical encounter:
      1) individualized and detailed health promotion, 2) counseling that promoted self
      efficacy, 3) pragmatic and practical self-care recommendations, 4) novel
      treatment options that fostered hopefulness, and 5) patient education that
      addressed both diabetes self-care and general health. A ninth theme was cross
      cutting: the contrast between ND care and conventional medical care. Results
      indicate that the routine clinical approach used by NDs is consistent with
      behavior change theory and clinical strategies found most effective in promoting
      self-efficacy and improving clinical outcomes.

PMID- 23144901
TI  - The importance of synergy between deep inspirations and fluidization in reversing
      airway closure.
AB  - Deep inspirations (DIs) and airway smooth muscle fluidization are two widely
      studied phenomena in asthma research, particularly for their ability (or
      inability) to counteract severe airway constriction. For example, DIs have been
      shown effectively to reverse airway constriction in normal subjects, but this is
      impaired in asthmatics. Fluidization is a connected phenomenon, wherein the
      ability of airway smooth muscle (ASM, which surrounds and constricts the airways)
      to exert force is decreased by applied strain. A maneuver which sufficiently
      strains the ASM, then, such as a DI, is thought to reduce the force generating
      capacity of the muscle via fluidization and hence reverse or prevent airway
      constriction. Understanding these two phenomena is considered key to
      understanding the pathophysiology of asthma and airway hyper-responsiveness, and
      while both have been extensively studied, the mechanism by which DIs fail in
      asthmatics remains elusive. Here we show for the first time the synergistic
      interaction between DIs and fluidization which allows the combination to provide
      near complete reversal of airway closure where neither is effective alone. This
      relies not just on the traditional model of airway bistability between open and
      closed states, but also the critical addition of previously-unknown oscillatory
      and chaotic dynamics. It also allows us to explore the types of subtle change
      which can cause this interaction to fail, and thus could provide the missing link
      to explain DI failure in asthmatics.

PMID- 23144902
TI  - Expectations modulate the magnitude of attentional capture by auditory events.
AB  - What determines the magnitude of attentional capture by deviant sound events? We
      combined the cross-modal oddball distraction paradigm with sequence learning to
      address this question. Participants responded to visual targets, each preceded by
      tones that formed a repetitive cross-trial standard sequence. In Experiment 1,
      with the standard tone sequence ...-660-440-660-880-... Hz, either the 440 Hz or
      the 880 Hz standard was occasionally replaced by one of two deviant tones (220 Hz
      and 1100 Hz), that either differed slightly (by 220 Hz) or markedly (by 660 Hz)
      from the replaced standard. In Experiment 2, with the standard tone sequence ...
      220-660-440-660-880-660-1100-... Hz, the 440 Hz and the 880 Hz standard was
      occasionally replaced by either a 220 Hz or a 1100 Hz pattern deviant. In both
      experiments, a high-pitch deviant was more captivating when it replaced a low
      pitch standard, and a low-pitch deviant was more captivating when it replaced a
      high-pitch standard. These results indicate that the magnitude of attentional
      capture by deviant sound events depends on the discrepancy between the deviant
      event and the expected event, not on perceived local change.

PMID- 23144903
TI  - Cryptococcus neoformans-derived microvesicles enhance the pathogenesis of fungal
      brain infection.
AB  - Cryptococcal meningoencephalitis is the most common fungal disease in the central
      nervous system. The mechanisms by which Cryptococcus neoformans invades the brain
      are largely unknown. In this study, we found that C. neoformans-derived
      microvesicles (CnMVs) can enhance the traversal of the blood-brain barrier (BBB)
      by C. neoformans invitro. The immunofluorescence imaging demonstrates that CnMVs
      can fuse with human brain microvascular endothelial cells (HBMECs), the
      constituents of the BBB. This activity is presumably due to the ability of the
      CnMVs to activate HBMEC membrane rafts and induce cell fusogenic activity. CnMVs
      also enhanced C. neoformans infection of the brain, found in both infected brains
      and cerebrospinal fluid. In infected mouse brains, CnMVs are distributed inside
      and around C. neoformans-induced cystic lesions. GFAP (glial fibrillary acidic
      protein)-positive astrocytes were found surrounding the cystic lesions,
      overlapping with the 14-3-3-GFP (14-3-3-green fluorescence protein fusion)
      signals. Substantial changes could be observed in areas that have a high density
      of CnMV staining. This is the first demonstration that C. neoformans-derived
      microvesicles can facilitate cryptococcal traversal across the BBB and accumulate
      at lesion sites of C. neoformans-infected brains. Results of this study suggested
      that CnMVs play an important role in the pathogenesis of cryptococcal
      meningoencephalitis.

PMID- 23144904
TI  - Cell surface galectin-9 expressing Th cells regulate Th17 and Foxp3+ Treg
      development by galectin-9 secretion.
AB  - Galectin-9 (Gal-9), a beta-galactoside binding mammalian lectin, regulates immune
      responses by reducing pro-inflammatory IL-17-producing Th cells (Th17) and
      increasing anti-inflammatory Foxp3(+) regulatory T cells (Treg) in vitro and in
      vivo. These functions of Gal-9 are thought to be exerted by binding to receptor
      molecules on the cell surface. However, Gal-9 lacks a signal peptide for
      secretion and is predominantly located in the cytoplasm, which raises questions
      regarding how and which cells secrete Gal-9 in vivo. Since Gal-9 expression does
      not necessarily correlate with its secretion, Gal-9-secreting cells in vivo have
      been elusive. We report here that CD4 T cells expressing Gal-9 on the cell
      surface (Gal-9(+) Th cells) secrete Gal-9 upon T cell receptor (TCR) stimulation,
      but other CD4 T cells do not, although they express an equivalent amount of
      intracellular Gal-9. Gal-9(+) Th cells expressed interleukin (IL)-10 and
      transforming growth factor (TGF)-beta but did not express Foxp3. In a co-culture
      experiment, Gal-9(+) Th cells regulated Th17/Treg development in a manner similar
      to that by exogenous Gal-9, during which the regulation by Gal-9(+) Th cells was
      shown to be sensitive to a Gal-9 antagonist but insensitive to IL-10 and TGF-beta
      blockades. Further elucidation of Gal-9(+) Th cells in humans indicates a
      conserved role of these cells through evolution and implies the possible utility
      of these cells for diagnosis or treatment of immunological diseases.

PMID- 23144905
TI  - Male-specific differences in proliferation, neurogenesis, and sensitivity to
      oxidative stress in neural progenitor cells derived from a rat model of ALS.
AB  - Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disease
      characterized by progressive motor dysfunction and the loss of large motor
      neurons in the spinal cord and brain stem. A clear genetic link to point
      mutations in the superoxide dismutase 1 (SOD1) gene has been shown in a small
      group of familial ALS patients. The exact etiology of ALS is still uncertain, but
      males have consistently been shown to be at a higher risk for the disease than
      females. Here we present male-specific effects of the mutant SOD1 transgene on
      proliferation, neurogenesis, and sensitivity to oxidative stress in rat neural
      progenitor cells (rNPCs). E14 pups were bred using SOD1(G93A) transgenic male
      rats and wild-type female rats. The spinal cord and cortex tissues were
      collected, genotyped by PCR using primers for the SOD1(G93A) transgene or the
      male-specific Sry gene, and cultured as neurospheres. The number of dividing
      cells was higher in male rNPCs compared to female rNPCs. However, SOD1(G93A) over
      expression significantly reduced cell proliferation in male cells but not female
      cells. Similarly, male rNPCs produced more neurons compared to female rNPCs, but
      SOD1(G93A) over-expression significantly reduced the number of neurons produced
      in male cells. Finally we asked whether sex and SOD1(G93A) transgenes affected
      sensitivity to oxidative stress. There was no sex-based difference in cell
      viability after treatment with hydrogen peroxide or 3-morpholinosydnonimine, a
      free radical-generating agent. However, increased cytotoxicity by SOD1(G93A) over
      expression occurred, especially in male rNPCs. These results provide essential
      information on how the mutant SOD1 gene and sexual dimorphism are involved in ALS
      disease progression.

PMID- 23144906
TI  - Suprabasin is hypomethylated and associated with metastasis in salivary adenoid
      cystic carcinoma.
AB  - BACKGROUND: Salivary gland adenoid cystic carcinoma (ACC) is a rare cancer,
      accounting for only 1% of all head and neck malignancies. ACC is well known for
      perineural invasion and distant metastasis, but its underlying molecular
      mechanisms of carcinogenesis are still unclear. PRINCIPAL FINDINGS: Here, we show
      that a novel oncogenic candidate, suprabasin (SBSN), plays important roles in
      maintaining the anchorage-independent and anchorage-dependent cell proliferation
      in ACC by using SBSN shRNA stably transfected ACC cell line clones. SBSN is also
      important in maintaining the invasive/metastatic capability in ACC by Matrigel
      invasion assay. More interestingly, SBSN transcription is significantly
      upregulated by DNA demethylation induced by 5-aza-2'-deoxycytidine plus
      trichostatin A treatment and the DNA methylation levels of the SBSN CpG island
      located in the second intron were validated to be significantly hypomethylated in
      primary ACC samples versus normal salivary gland tissues.
      CONCLUSIONS/SIGNIFICANCE: Taken together, these results support SBSN as novel
      oncogene candidate in ACC, and the methylation changes could be a promising
      biomarker for ACC.

PMID- 23144907
TI  - On the ontology based representation of cell lines.
AB  - Cell lines are frequently used as highly standardized and reproducible in vitro
      models for biomedical analyses and assays. Cell lines are distributed by cell
      banks that operate databases describing their products. However, the description
      of the cell lines' properties are not standardized across different cell banks.
      Existing cell line-related ontologies mostly focus on the description of the cell
      lines' names, but do not cover aspects like the origin or optimal growth
      conditions. The objective of this work is to develop an ontology that allows for
      a more comprehensive description of cell lines and their metadata, which should
      cover the data elements provided by cell banks. This will provide the basis for
      the standardized annotation of cell lines and corresponding assays in biomedical
      research. In addition, the ontology will be the foundation for automated
      evaluation of such assays and their respective protocols in the future. To
      accomplish this, a broad range of cell bank databases as well as existing
      ontologies were analyzed in a comprehensive manner. We identified existing
      ontologies capable of covering different aspects of the cell line domain.
      However, not all data fields derived from the cell banks' databases could be
      mapped to existing ontologies. As a result, we created a new ontology called cell
      culture ontology (CCONT) integrating existing ontologies where possible. CCONT
      provides classes from the areas of cell line identification, origin, cell line
      properties, propagation and tests performed.

PMID- 23144908
TI  - Immunogenicity and acceptance of influenza A (H1N1) vaccine in a cohort of
      chronic hepatitis C patients receiving pegylated-interferon treatment.
AB  - BACKGROUND #ENTITYSTARTX00026; AIMS: Individuals at risk of (H1N1) influenza A
      infection are recommended to receive vaccination. Chronic hepatitis C (CHC)
      patients receiving treatment might be at a higher risk of respiratory bacterial
      infections after influenza infection. However, there are no observational studies
      evaluating the immunogenicity, tolerance and acceptance of 2009 influenza A
      vaccine in CHC patients. METHODS: We evaluated the immunogenicity of influenza A
      vaccine (Pandemrix(r)) by using the hemagglutination inhibition (HI) titers
      method in a well defined cohort of CHC patients receiving or not receiving
      pegylated-interferon and ribavirin, and compared it with healthy subjects
      (controls). A group of patients with inflammatory bowel disease (IBD) under
      immunosuppression, thought to have a lower immune response to seasonal influenza
      vaccine, were also included as a negative control group. In addition, tolerance
      to injection site reactions and acceptance was assessed by a validated
      questionnaire (Vaccinees' perception of injection-VAPI-questionnaire). RESULTS:
      Of 114 subjects invited to participate, 68% accepted and, after exclusions, 72
      were included. Post-vaccination geometric mean titers and
      seroprotection/seroconversion rates were optimal in CHC patients with ongoing
      treatment (n = 15; 232, CI95% 46-1166; 93%; 93%), without treatment (n = 10; 226,
      CI95% 69-743: 100%; 100%) and controls (n = 15;168, CI95% 42-680; 93%; 86%) with
      no differences between groups (P = 0.8). In contrast, IBD patients had a
      significantly lower immunogenic response (n = 27; 60, CI95% 42-680;66%;66%; P =
      0.006). All the groups showed a satisfactory tolerance although CHC patients with
      ongoing treatment showed more local discomfort after vaccine injection.
      CONCLUSION: There appeared to be no differences between CHC patients and healthy
      controls in serological response and acceptance of (H1N1) influenza vaccination.

PMID- 23144909
TI  - Treatment with the proteasome inhibitor MG132 during the end of oocyte maturation
      improves oocyte competence for development after fertilization in cattle.
AB  - Maturation of the oocyte involves nuclear and cytoplasmic changes that include
      post-translational processing of proteins. The objective was to investigate
      whether inhibition of proteasomes during maturation would alter competence of the
      bovine oocyte for fertilization and subsequent development. Cumulus-oocyte
      complexes were cultured in the presence or absence of the proteasomal inhibitor
      MG132 from either 0-6 h or 16-22 h after initiation of maturation. Treatment with
      MG132 early in maturation prevented progression to meiosis II and reduced
      fertilization rate and the proportion of oocytes and cleaved embryos that became
      blastocysts. Conversely, treatment with MG132 late in maturation improved the
      percentage of oocytes and cleaved embryos that became blastocysts without
      affecting nuclear maturation or fertilization rate. Optimal results with MG132
      were achieved at a concentration of 10 uM - effects were generally not observed
      at lower or higher concentrations. Using proteomic analysis, it was found that
      MG132 at the end of maturation increased relative expression of 6 proteins and
      decreased relative expression of 23. Among those increased by MG132 that are
      potentially important for oocyte competence are GAPDH, involved in glycolysis,
      TUBA1C, needed for organellar movement, and two proteins involved in protein
      folding (P4HB and HYOU1). MG132 decreased amounts of several proteins that exert
      anti-apoptotic actions including ASNS, HSP90B1, PDIA3 and VCP. Another protein
      decreased by MG132, CDK5, can lead to apoptosis if aberrantly activated and one
      protein increased by MG132, P4HB, is anti-apoptotic. Finally, the pregnancy rate
      of cows receiving embryos produced from oocytes treated with MG132 from 16-22 h
      of maturation was similar to that for control embryos, suggesting that use of
      MG132 for production of embryos in vitro does not cause a substantial decrease in
      embryo quality.

PMID- 23144910
TI  - A super TLR agonist to improve efficacy of dendritic cell vaccine in induction of
      anti-HCV immunity.
AB  - Persistent infections caused by pathogens such as hepatitis C virus are major
      human diseases with limited or suboptimal prophylactic and therapeutic options.
      Given the critical role of dendritic cell (DC) in inducing immune responses, DC
      vaccination is an attractive means to prevent and control the occurrence and
      persistence of the infections. However, DCs are built-in with inherent negative
      regulation mechanisms which attenuate their immune stimulatory activity and lead
      to their ineffectiveness in clinical application. In this study, we developed a
      super DC stimulant that consists of a modified, secretory Toll-like Receptor
      (TLR)-5 ligand and an inhibitor of the negative regulator, suppressor of cytokine
      sinaling-1 (SOCS1). We found that expressing the super stimulant in DCs is
      drastically more potent and persistent than using the commonly used DC stimuli to
      enhance the level and duration of inflammatory cytokine production by both murine
      and human DCs. Moreover, the DCs expressing the super stimulant are more potent
      to provoke both cellular and humoral immune responses against hepatitis C virus
      (HCV) antigen in vivo. Thus, the strategy capable of triggering and sustaining
      proinflammatory status of DCs may be used to boost efficiency of DC vaccine in
      preventing and combating the persistent infection of HCV or other chronic
      viruses.

PMID- 23144911
TI  - Real-time monitoring of photocytotoxicity in nanoparticles-based photodynamic
      therapy: a model-based approach.
AB  - Nanoparticles are widely suggested as targeted drug-delivery systems. In
      photodynamic therapy (PDT), the use of multifunctional nanoparticles as
      photoactivatable drug carriers is a promising approach for improving treatment
      efficiency and selectivity. However, the conventional cytotoxicity assays are not
      well adapted to characterize nanoparticles cytotoxic effects and to discriminate
      early and late cell responses. In this work, we evaluated a real-time label-free
      cell analysis system as a tool to investigate in vitro cyto- and photocyto
      toxicity of nanoparticles-based photosensitizers compared with classical
      metabolic assays. To do so, we introduced a dynamic approach based on real-time
      cell impedance monitoring and a mathematical model-based analysis to characterize
      the measured dynamic cell response. Analysis of real-time cell responses requires
      indeed new modeling approaches able to describe suited use of dynamic models. In
      a first step, a multivariate analysis of variance associated with a canonical
      analysis of the obtained normalized cell index (NCI) values allowed us to
      identify different relevant time periods following nanoparticles exposure. After
      light irradiation, we evidenced discriminant profiles of cell index (CI) kinetics
      in a concentration- and light dose-dependent manner. In a second step, we
      proposed a full factorial design of experiments associated with a mixed effect
      kinetic model of the CI time responses. The estimated model parameters led to a
      new characterization of the dynamic cell responses such as the magnitude and the
      time constant of the transient phase in response to the photo-induced dynamic
      effects. These parameters allowed us to characterize totally the in vitro
      photodynamic response according to nanoparticle-grafted photosensitizer
      concentration and light dose. They also let us estimate the strength of the
      synergic photodynamic effect. This dynamic approach based on statistical modeling
      furnishes new insights for in vitro characterization of nanoparticles-mediated
      effects on cell proliferation with or without light irradiation.

PMID- 23144912
TI  - DNA repair and cell cycle biomarkers of radiation exposure and inflammation
      stress in human blood.
AB  - DNA damage and repair are hallmarks of cellular responses to ionizing radiation.
      We hypothesized that monitoring the expression of DNA repair-associated genes
      would enhance the detection of individuals exposed to radiation versus other
      forms of physiological stress. We employed the human blood ex vivo radiation
      model to investigate the expression responses of DNA repair genes in repeated
      blood samples from healthy, non-smoking men and women exposed to 2 Gy of X-rays
      in the context of inflammation stress mimicked by the bacterial endotoxin
      lipopolysaccharide (LPS). Radiation exposure significantly modulated the
      transcript expression of 12 genes of 40 tested (2.2E-06<p<0.03), of which 8
      showed no overlap between unirradiated and irradiated samples (CDKN1A, FDXR,
      BBC3, PCNA, GADD45a, XPC, POLH and DDB2). This panel demonstrated excellent dose
      response discrimination (0.5 to 8 Gy) in an independent human blood ex vivo
      dataset, and 100% accuracy for discriminating patients who received total body
      radiation. Three genes of this panel (CDKN1A, FDXR and BBC3) were also highly
      sensitive to LPS treatment in the absence of radiation exposure, and LPS co
      treatment significantly affected their radiation responses. At the protein level,
      BAX and pCHK2-thr68 were elevated after radiation exposure, but the pCHK2-thr68
      response was significantly decreased in the presence of LPS. Our combined panel
      yields an estimated 4-group accuracy of ~90% to discriminate between radiation
      alone, inflammation alone, or combined exposures. Our findings suggest that DNA
      repair gene expression may be helpful to identify biodosimeters of exposure to
      radiation, especially within high-complexity exposure scenarios.

PMID- 23144913
TI  - Load-relaxation properties of the human trunk in response to prolonged flexion:
      measuring and modeling the effect of flexion angle.
AB  - Experimental studies suggest that prolonged trunk flexion reduces passive support
      of the spine. To understand alterations of the synergy between active and passive
      tissues following such loadings, several studies have assessed the time-dependent
      behavior of passive tissues including those within spinal motion segments and
      muscles. Yet, there remain limitations regarding load-relaxation of the lumbar
      spine in response to flexion exposures and the influence of different flexion
      angles. Ten healthy participants were exposed for 16 min to each of five
      magnitudes of lumbar flexion specified relative to individual flexion-relaxation
      angles (i.e., 30, 40, 60, 80, and 100%), during which lumbar flexion angle and
      trunk moment were recorded. Outcome measures were initial trunk moment, moment
      drop, parameters of four viscoelastic models (i.e., Standard Linear Solid model,
      the Prony Series, Schapery's Theory, and the Modified Superposition Method), and
      changes in neutral zone and viscoelastic state following exposure. There were
      significant effects of flexion angle on initial moment, moment drop, changes in
      normalized neutral zone, and some parameters of the Standard Linear Solid model.
      Initial moment, moment drop, and changes in normalized neutral zone increased
      exponentially with flexion angle. Kelvin-solid models produced better predictions
      of temporal behaviors. Observed responses to trunk flexion suggest nonlinearity
      in viscoelastic properties, and which likely reflected viscoelastic behaviors of
      spinal (lumbar) motion segments. Flexion-induced changes in viscous properties
      and neutral zone imply an increase in internal loads and perhaps increased risk
      of low back disorders. Kelvin-solid models, especially the Prony Series model
      appeared to be more effective at modeling load-relaxation of the trunk.

PMID- 23144914
TI  - Endoplasmic reticulum redox state is not perturbed by pharmacological or
      pathological endoplasmic reticulum stress in live pancreatic beta-cells.
AB  - Accumulation of unfolded, misfolded and aggregated proteins in the endoplasmic
      reticulum (ER) causes ER stress. ER stress can result from physiological
      situations such as acute increases in secretory protein biosynthesis or
      pathological conditions that perturb ER homeostasis such as alterations in the ER
      redox state. Here we monitored ER redox together with transcriptional output of
      the Unfolded Protein Response (UPR) in INS-1 insulinoma cells stably expressing
      eroGFP (ER-redox-sensor) and mCherry protein driven by a GRP78 promoter (UPR
      sensor). Live cell imaging, flow cytometry and biochemical characterization were
      used to examine these parameters in response to various conditions known to
      induce ER stress. As expected, treatment of the cells with the reducing agent
      dithiothreitol caused a decrease in the oxidation state of the ER accompanied by
      an increase in XBP-1 splicing. Unexpectedly however, other treatments including
      tunicamycin, thapsigargin, DL-homocysteine, elevated free fatty acids or high
      glucose had essentially no influence on the ER redox state, despite inducing ER
      stress. Comparable results were obtained with dispersed rat islet cells
      expressing eroGFP. Thus, unlike in yeast cells, ER stress in pancreatic beta
      cells is not associated with a more reducing ER environment.

PMID- 23144915
TI  - The neural correlates of identity faking and concealment: an FMRI study.
AB  - The neural basis of self and identity has received extensive research. However,
      most of these existing studies have focused on situations where the internal
      representation of the self is consistent with the external one. The present study
      used fMRI methodology to examine the neural correlates of two different types of
      identity conflict: identity faking and concealment. Participants were presented
      with a sequence of names and asked to either conceal their own identity or fake
      another one. The results revealed that the right insular cortex and bilaterally
      inferior frontal gyrus were more active for identity concealment compared to the
      control condition, whereas identity faking elicited a significantly larger
      percentage signal increase than the control condition in the right superior
      frontal gyrus, left calcarine, and right caudate. These results suggest that
      different neural systems associated with both identity processing and deception
      were involved in identity concealment and faking.

PMID- 23144917
TI  - Histological criteria for encapsulating peritoneal sclerosis - a standardized
      approach.
AB  - BACKGROUND: The two most relevant pathologies of long-term peritoneal dialysis
      (PD) are simple sclerosis and encapsulating peritoneal sclerosis (EPS). The
      histological differentiation of those two entities is difficult. The Aim of the
      study was to establish a method to standardize and facilitate the differentiation
      between simple sclerosis and EPS  METHODS: We investigated 58 peritoneal biopsies
      - 31 EPS patients and 27 PD patients. Two blinded investigators analyzed 20
      histological characteristics in EPS and PD patients. RESULTS: THE FOLLOWING
      FINDINGS WERE SIGNIFICANTLY MORE COMMON IN EPS THAN IN PATIENTS ON PD WITHOUT
      EPS: fibroblast like cells (FLC) (p<0.0001), mesothelial denudation (p<0.0001),
      decreased cellularity (p = 0.008), fibrin deposits (p<0.03), Fe deposits (p =
      0.05), podoplanin vascular (p<0.0001), podoplanin avascular (p<0.0001). Using all
      predictor variables we trained the classification method Random Forest to
      categorize future cases. Podoplanin vascular and avascular were taken together
      (p<0.0001), FLC (p<0.0001), mesothelial denudation (p = 0.0005), calcification (p
      = 0.0026), acellular areas (p = 0.0094), and fibrin deposits (p = 0.0336) showed
      up as significantly important predictor variables. Estimated misclassification
      error rate when classifying new cases turned out to be 14%. CONCLUSION: The
      introduced statistical method allows discriminating between simple sclerosis and
      EPS. The misclassification error will likely improve with every new case added to
      the database.

PMID- 23144918
TI  - Pericyte-like progenitors show high immaturity and engraftment potential as
      compared with mesenchymal stem cells.
AB  - Mesenchymal stem cells (MSCs) and pericyte progenitors (PPs) are both
      perivascular cells with similar multipotential properties regardless of tissue of
      origin. We compared the phenotype and function of the 2 cell types derived from
      the same bone-marrow samples but expanded in their respective media - pericyte
      conditions (endothelial cell growth medium 2 [EGM-2]) for PPs and standard medium
      (mesenchymal stem cell medium [MSM]) for MSCs. After 3 weeks of culture, whatever
      the expansion medium, all cells showed similar characteristics (MSC markers and
      adipo-osteo-chondroblastic differentiation potential), although neuronal
      potential was greater in EGM-2- than MSM-cultured cells. As compared with MSM
      cultured MSCs, EGM-2-cultured PPs showed higher expression of the pericyte
      specific antigen 3G5 than alpha-smooth muscle actin. In addition, EGM-2-cultured
      PPs showed an immature phenotype, with upregulation of stemness OCT4 and SOX2
      proteins and downregulation of markers of osteoblastic, chondroblastic,
      adipocytic and vascular smooth muscle lineages. Despite having less effective in
      vitro immunosuppression capacities than standard MSCs, EGM-2-cultured PPs had
      higher engraftment potentials when combined with biomaterials heterotopically
      transplanted in Nude mice. Furthermore, these engrafted cells generated more
      collagen matrix and were preferentially perivascular or lined trabeculae as
      compared with MSM-cultured MSCs. In conclusion, EGM-2-cultured PPs are highly
      immature cells with increased plasticity and engraftment potential.

PMID- 23144919
TI  - Py2T murine breast cancer cells, a versatile model of TGFbeta-induced EMT in
      vitro and in vivo.
AB  - INTRODUCTION: Increasing evidence supports a role of an epithelial to mesenchymal
      transition (EMT) process in endowing subsets of tumor cells with properties
      driving malignant tumor progression and resistance to cancer therapy. To advance
      our understanding of the underlying mechanisms, we sought to generate a
      transplantable cellular model system that allows defined experimental
      manipulation and analysis of EMT in vitro and at the same time recapitulates
      oncogenic EMT in vivo. METHODOLOGY/RESULTS: We have established a stable murine
      breast cancer cell line (Py2T) from a breast tumor of an MMTV-PyMT transgenic
      mouse. Py2T cells display a metastable epithelial phenotype characterized by
      concomitant expression of luminal and basal cytokeratins and sheet migration.
      Exposure of Py2T cells to transforming growth factor beta (TGFbeta) in vitro
      induces reversible EMT accompanied by downregulation of E-cadherin and
      upregulation of mesenchymal markers, including EMT transcription factors, and a
      gain in single cell motility and invasiveness. Py2T cells give rise to tumors
      after orthotopic injection into syngeneic FVB/N mice. Notably, transplantation of
      epithelial Py2T cells results in the formation of invasive primary tumors with
      low to absent E-cadherin expression, indicating that the cells undergo EMT-like
      changes in vivo. This process appears to at least in part depend on TGFbeta
      signaling, since tumors formed by Py2T cells expressing a dominant-negative
      version of TGFbeta receptor widely maintain their epithelial differentiation
      status. CONCLUSIONS/SIGNIFICANCE: Together, the data demonstrate that the Py2T
      cell line represents a versatile model system to study the EMT process in vitro
      and in vivo. The observation that Py2T cells give rise to tumors and collectively
      undergo EMT-like changes in vivo highlights the suitability of the Py2T model
      system as a tool to study tumor-related EMT. In particular, Py2T cells may serve
      to corroborate recent findings relating EMT to cancer cell stemness, to therapy
      resistance and to tumor recurrence.

PMID- 23144920
TI  - Inter-hemispheric oscillations in human sleep.
AB  - Sleep is generally categorized into discrete stages based on characteristic
      electroencephalogram (EEG) patterns. This traditional approach represents sleep
      architecture in a static way, but it cannot reflect variations in sleep across
      time and across the cortex. To investigate these dynamic aspects of sleep, we
      analyzed sleep recordings in 14 healthy volunteers with a novel, frequency-based
      EEG analysis. This approach enabled comparison of sleep patterns with low inter
      individual variability. We then implemented a new probability dependent,
      automatic classification of sleep states that agreed closely with conventional
      manual scoring during consolidated sleep. Furthermore, this analysis revealed a
      previously unrecognized, interhemispheric oscillation during rapid eye movement
      (REM) sleep. This quantitative approach provides a new way of examining the
      dynamic aspects of sleep, shedding new light on the physiology of human sleep.

PMID- 23144921
TI  - Water stress and aphid feeding differentially influence metabolite composition in
      Arabidopsis thaliana (L.).
AB  - Little is known about how drought stress influences plant secondary metabolite
      accumulation and how this affects plant defense against different aphids. We
      therefore cultivated Arabidopsis thaliana (L.) plants under well-watered,
      drought, and water-logged conditions. Two aphid species were selected for this
      study: the generalist Myzus persicae (Sulzer) and the crucifer specialist
      Brevicoryne brassicae (L.). Metabolite concentrations in the phloem sap, which
      influence aphid growth, changed particularly under drought stress. Levels of
      sucrose and several amino acids, such as glutamic acid, proline, isoleucine, and
      lysine increased, while concentrations of 4-methoxyindol-3-ylmethyl glucosinolate
      decreased. M. persicae population growth was highest on plants under drought
      stress conditions. However, B. brassicae did not profit from improved phloem sap
      quality under drought stress and performed equally in all water treatments. Water
      stress and aphids generally had an opposite effect on the accumulation of
      secondary metabolites in the plant rosettes. Drought stress and water-logging led
      to increased aliphatic glucosinolate and flavonoid levels. Conversely, aphid
      feeding, especially of M. persicae, reduced levels of flavonoids and
      glucosinolates in the plants. Correspondingly, transcript levels of aliphatic
      biosynthetic genes decreased after feeding of both aphid species. Contrary to M.
      persicae, drought stress did not promote population growth of B. brassicae on
      these plants. The specialist aphid induced expression of CYP79B2, CYP79B3, and
      PAD3 with corresponding accumulation of indolyl glucosinolates and camalexin.
      This was distinct from M. persicae, which did not elicit similarly strong
      camalexin accumulation, which led to the hypothesis of a specific defense
      adaptations against the specialist aphid.

PMID- 23144916
TI  - Genetic responses induced in olive roots upon colonization by the biocontrol
      endophytic bacterium Pseudomonas fluorescens PICF7.
AB  - Knowledge on the genetic basis underlying interactions between beneficial
      bacteria and woody plants is still very limited, and totally absent in the case
      of olive. We aimed to elucidate genetic responses taking place during the
      colonization of olive roots by the native endophyte Pseudomonas fluorescens
      PICF7, an effective biocontrol agent against Verticillium wilt of olive. Roots of
      olive plants grown under non-gnotobiotic conditions were collected at different
      time points after PICF7 inoculation. A Suppression Subtractive Hybridization cDNA
      library enriched in induced genes was generated. Quantitative real time PCR (qRT
      PCR) analysis validated the induction of selected olive genes. Computational
      analysis of 445 olive ESTs showed that plant defence and response to different
      stresses represented nearly 45% of genes induced in PICF7-colonized olive roots.
      Moreover, quantitative real-time PCR (qRT-PCR) analysis confirmed induction of
      lipoxygenase, phenylpropanoid, terpenoids and plant hormones biosynthesis
      transcripts. Different classes of transcription factors (i.e., bHLH, WRKYs,
      GRAS1) were also induced. This work highlights for the first time the ability of
      an endophytic Pseudomonas spp. strain to mount a wide array of defence responses
      in an economically-relevant woody crop such as olive, helping to explain its
      biocontrol activity.

PMID- 23144923
TI  - Head lice surveillance on a deregulated OTC-sales market: a study using web query
      data.
AB  - The head louse, Pediculus humanus capitis, is an obligate ectoparasite that
      causes infestations of humans. Studies have demonstrated a correlation between
      sales figures for over-the-counter (OTC) treatment products and the number of
      humans with head lice. The deregulation of the Swedish pharmacy market on July 1,
      2009, decreased the possibility to obtain complete sale figures and thereby the
      possibility to obtain yearly trends of head lice infestations. In the presented
      study we wanted to investigate whether web queries on head lice can be used as
      substitute for OTC sales figures. Via Google Insights for Search and Vardguiden
      medical web site, the number of queries on "huvudloss" (head lice) and "harloss"
      (lice in hair) were obtained. The analysis showed that both the Vardguiden series
      and the Google series were statistically significant (p<0.001) when added
      separately, but if the Google series were already included in the model, the
      Vardguiden series were not statistically significant (p = 0.5689). In conclusion,
      web queries can detect if there is an increase or decrease of head lice infested
      humans in Sweden over a period of years, and be as reliable a proxy as the OTC
      sales figures.

PMID- 23144922
TI  - Low dose nicotine and antagonism of beta2 subunit containing nicotinic
      acetylcholine receptors have similar effects on affective behavior in mice.
AB  - Nicotine leads to both activation and desensitization (inactivation) of nicotinic
      acetylcholine receptors (nAChRs). This study tested the hypothesis that nicotine
      and a selective antagonist of beta2*nAChRs would have similar effects on
      affective behavior. Adult C57BL/6J male mice were tested in a conditioned
      emotional response (CER) assay which evaluates the ability of an aversive
      stimulus to inhibit goal-directed behavior. Mice lever-pressed for a saccharin
      reinforcer according to a variable schedule of reinforcement during sessions in
      which two presentations of a compound light/tone conditioned stimulus (CS) co
      terminated with a 0.1 or 0.3 mA, 0.5 s footshock unconditioned stimulus (US).
      During testing in the absence of the US, mice received doses of i.p. nicotine (0,
      0.0032, 0.01, 0.032, 0.1 mg/kg) or a selective beta2 subunit containing nAChR
      (beta2*nAChR) antagonist dihydro-beta-erythroidine (0, 0.1, 0.3, 1.0, 3.0 mg/kg
      DHbetaE). There was a dose-dependent effect of nicotine revealing that only low
      doses (0.01, 0.032 mg/kg) increased CER suppression ratios (SR) in these mice.
      DHbetaE also dose-dependently increased SR at the 3 mg/kg dose. In ethological
      measures of fear-/anxiety-like behavior, these doses of nicotine and DHbetaE
      significantly reduced digging behavior in a marble burying task and 0.3 mg/kg
      DHbetaE promoted open-arm activity in the elevated plus maze. Doses of nicotine
      and DHbetaE that altered affective behavior had no effect on locomotor activity.
      Similar to previous reports with anxiolytic drugs, low dose nicotine and DHbetaE
      reversed SR in a CER assay, decreased digging in a marble burying assay and
      increased open arm activity in the elevated plus maze. This study provides
      evidence that inactivation of beta2*nAChRs reduces fear-like and anxiety-like
      behavior in rodents and suggests that smokers may be motivated to smoke in part
      to desensitize their beta2*nAChRs. These data further identify beta2*nAChR
      antagonism as a potential therapeutic strategy for relief of negative affect and
      anxiety.

PMID- 23144924
TI  - Inhibition of tankyrases induces Axin stabilization and blocks Wnt signalling in
      breast cancer cells.
AB  - Constitutive Wnt signalling is characterized by excessive levels of beta-catenin
      protein and is a frequent occurrence in cancer. APC and Axin are key components
      of the beta-catenin destruction complex that acts to promote beta-catenin
      degradation. The levels of Axin are in turn controlled by tankyrases, members of
      the PARP-family of poly-ADP-ribosylation enzymes. In colorectal cancer cells,
      which typically harbor APC mutations, inhibition of tankyrase activity promotes
      Axin stabilization and attenuates Wnt signalling. Here, we examined the effect of
      inhibiting tankyrases in breast cancer cells with normal APC. We show that
      application of the small molecule tankyrase inhibitor, XAV939 or siRNA-mediated
      abrogation of tankyrase expression increases Axin1 and Axin2 protein levels and
      attenuates Wnt-induced transcriptional responses in several breast cancer lines.
      In MDA-MB-231 cells, inhibiton of tankyrase activity also attenuate Wnt3a induced
      cell migration. Moreover, in both MDA-MB-231 and colorectal cancer cells, XAV939
      inhibits cell growth under conditions of serum-deprivation. However, the presence
      of serum prevents this growth inhibitory effect, although inhibition of Wnt
      induced transcriptional and migratory responses was maintained. These results
      indicate that stabilization of Axin by inhibition of tankyrases alone, may not be
      an effective means to block tumor cell growth and that combinatorial therapeutic
      approaches should be considered.

PMID- 23144925
TI  - Tetracycline inhibits local inflammation induced by cerebral ischemia via
      modulating autophagy.
AB  - BACKGROUND: Tetracycline exerts neuroprotection via suppressing the local
      inflammation induced by cerebral ischemia. However, the underlying mechanism is
      not completely clear. METHODOLOGY/PRINCIPAL FINDINGS: The mRNA and protein
      expressions of tumor necrosis factor alpha and interleukin 6 and the number of
      activated microglia were measured to detect the inflammatory process in the
      ischemic hemisphere. The key proteins of nuclear factor kappa B pathway and the
      binding activity of nuclear factor kappa B were also measured. Two key components
      of autophagy, Beclin 1 and LC3, were detected by western blotting. Pretreatment
      with tetracycline inhibited the mRNA and protein expressions of tumor necrosis
      factor alpha and interleukin 6 and decreased the numbers of activated and
      phagocytotic microglia. Tetracycline down regulated the total and phosphorylated
      expressions of IKK, IkappaB and p65 (P<0.05). The autophagy inhibitor, 3
      methyladenine, inhibited inflammation and activation of nuclear factor kappa B
      pathway. The levels of Beclin 1 and LC3 were decreased by 3-methyladenine and
      tetracycline. CONCLUSIONS/SIGNIFICANCE: Our data suggested that pretreatment of
      tetracycline may inhibit autophagy in the ischemic stroke brain and then suppress
      the inflammatory process via inhibiting the activation of nuclear factor kappa B
      pathway.

PMID- 23144926
TI  - Histone acetylase inhibitor curcumin impairs mouse spermiogenesis-an in vitro
      study.
AB  - In the previous study, we unraveled the unique "erasure strategy" during the
      mouse spermiogenesis. Chromatin associated proteins sequentially disassociated
      from the spermatid chromosome, which led to the termination of transcription in
      elongating spermatids. By this process, a relatively naive paternal chromatin was
      generated, which might be essential for the zygotic development. We supposed the
      regulation of histone acetylation played an important role throughout this
      "erasure" process. In order to verify this hypothesis, we treated mouse
      spermatids in vitro by histone acetylase (HAT) inhibitor Curcumin. Our results
      showed an inhibiting effect of Curcumin on the growth of germ cell line in a dose
      dependent manner. Accordingly, the apoptosis of primary haploid spermtids was
      increased by Curcumin treatment. As expected, the acetylated histone level was
      downregulated. Furthermore, we found the transcription in spermatids ceased in
      advance, the dynamics of chromatin associated factors was disturbed by Curcumin
      treatment. The regulation of histone acetylation should be one of the core
      reprogramming mechanisms during the spermiogenesis. The reproductive toxicity of
      Curcumin needs to be thoroughly investigated, which is crucial for its further
      clinical application.

PMID- 23144927
TI  - Meta-analysis of gadoxetic acid disodium (Gd-EOB-DTPA)-enhanced magnetic
      resonance imaging for the detection of liver metastases.
AB  - OBJECTIVE: To determine the accuracy of MR imaging with Gd-EOB-DTPA for the
      detection of liver metastases. MATERIALS AND METHODS: PUBMED, EMBASE, the Web of
      Science, and the Cochrane Library were searched for original articles published
      prior to February 2012. The criteria for the inclusion of articles were as
      follows: reported in the English language; MR imaging with Gd-EOB-DTPA was
      performed to detect liver metastases; histopathologic analysis (surgery, biopsy),
      intraoperative observation (manual palpatation, intraoperative ultrasonography),
      and/or follow-up US was the reference standard; and data were sufficient for the
      calculation of true-positive or false-negative values. The methodological quality
      was assessed by using the quality assessment of diagnostic studies instrument.
      The data were extracted to calculate sensitivity, specificity, predictive value,
      diagnostic odds ratio, and areas under hierarchical summary receiver operating
      characteristic (HSROC) curve to perform heterogeneity test and threshold effect
      test, as well as publication bias analysis and subgroup analyses. RESULTS: From
      229 citations, 13 were included in the meta-analysis with a total of 1900
      lesions. We detected heterogeneity between studies and evidence of publication
      bias. The methodological quality was moderate. The pooled weighted sensitivity
      with a corresponding 95% confidence interval (CI) was 0.93 (95% CI: 0.90, 0. 95),
      the specificity was 0.95 (95% CI: 0.91, 0.97), the positive likelihood ratio was
      18.07 (95% CI: 10.52, 31.04), the negative likelihood ratio was 0.07 (95% CI:
      0.05, 0.10), and the diagnostic odds ratio was 249.81 (95% CI: 125.12, 498.74).
      The area under the receiver operator characteristic curve was 0.98 (95% CI: 0.96,
      0.99). CONCLUSION: MR imaging with Gd-EOB-DTPA is a reliable, non-invasive, and
      no-radiation-exposure imaging modality with a high sensitivity and specificity
      for detection of liver metastases. Nonetheless, it should be applied cautiously,
      and large scale, well-designed trials are necessary to assess its clinical value.

PMID- 23144929
TI  - Visual diet versus associative learning as mechanisms of change in body size
      preferences.
AB  - Systematic differences between populations in their preferences for body size may
      arise as a result of an adaptive 'prepared learning' mechanism, whereby cues to
      health or status in the local population are internalized and affect body
      preferences. Alternatively, differences between populations may reflect their
      'visual diet' as a cognitive byproduct of mere exposure. Here we test the
      relative importance of these two explanations for variation in body preferences.
      Two studies were conducted where female observers were exposed to pictures of
      high or low BMI women which were either aspirational (healthy, attractive models
      in high status clothes) or non-aspirational (eating disordered patients in grey
      leotards), or to combinations thereof, in order to manipulate their body-weight
      preferences which were tested at baseline and at post-test. Overall, results
      showed good support for visual diet effects (seeing a string of small or large
      bodies resulted in a change from pre- to post-test whether the bodies were
      aspirational or not) and also some support for the associative learning
      explanation (exposure to aspirational images of overweight women induced a
      towards preferring larger bodies, even when accompanied by equal exposure to
      lower weight bodies in the non-aspirational category). Thus, both influences may
      act in parallel.

PMID- 23144928
TI  - Inhibition of both protease and helicase activities of hepatitis C virus NS3 by
      an ethyl acetate extract of marine sponge Amphimedon sp.
AB  - Combination therapy with ribavirin, interferon, and viral protease inhibitors
      could be expected to elicit a high level of sustained virologic response in
      patients infected with hepatitis C virus (HCV). However, several severe side
      effects of this combination therapy have been encountered in clinical trials. In
      order to develop more effective and safer anti-HCV compounds, we employed the
      replicon systems derived from several strains of HCV to screen 84 extracts from
      54 organisms that were gathered from the sea surrounding Okinawa Prefecture,
      Japan. The ethyl acetate-soluble extract that was prepared from marine sponge
      Amphimedon sp. showed the highest inhibitory effect on viral replication, with
      EC50 values of 1.5 and 24.9 ug/ml in sub-genomic replicon cell lines derived from
      genotypes 1b and 2a, respectively. But the extract had no effect on interferon
      inducing signaling or cytotoxicity. Treatment with the extract inhibited virus
      production by 30% relative to the control in the JFH1-Huh7 cell culture system.
      The in vitro enzymological assays revealed that treatment with the extract
      suppressed both helicase and protease activities of NS3 with IC50 values of 18.9
      and 10.9 ug/ml, respectively. Treatment with the extract of Amphimedon sp.
      inhibited RNA-binding ability but not ATPase activity. These results suggest that
      the novel compound(s) included in Amphimedon sp. can target the protease and
      helicase activities of HCV NS3.

PMID- 23144931
TI  - Diminazene aceturate (Berenil) modulates the host cellular and inflammatory
      responses to Trypanosoma congolense infection.
AB  - BACKGROUND: Trypanosoma congolense are extracellular and intravascular blood
      parasites that cause debilitating acute or chronic disease in cattle and other
      domestic animals. Diminazene aceturate (Berenil) has been widely used as a
      chemotherapeutic agent for trypanosomiasis in livestock since 1955. As in
      livestock, treatment of infected highly susceptible BALB/c mice with Berenil
      leads to rapid control of parasitemia and survival from an otherwise lethal
      infection. The molecular and biochemical mechanisms of action of Berenil are
      still not very well defined and its effect on the host immune system has remained
      relatively unstudied. Here, we investigated whether Berenil has, in addition to
      its trypanolytic effect, a modulatory effect on the host immune response to
      Trypanosoma congolense. METHODOLOGY/PRINCIPAL FINDINGS: BALB/c and C57BL/6 mice
      were infected intraperitoneally with T. congolense, treated with Berenil and the
      expression of CD25 and FoxP3 on splenic cells was assessed directly ex vivo. In
      addition, serum levels and spontaneous and LPS-induced production of pro
      inflammatory cytokines by splenic and hepatic CD11b+ cells were determined by
      ELISA. Berenil treatment significantly reduced the percentages of CD25+ cells, a
      concomitant reduction in the percentage of regulatory (CD4+Foxp3+) T cells and a
      striking reduction in serum levels of disease exacerbating pro-inflammatory
      cytokines including IL-6, IL-12, TNF and IFN-gamma. Furthermore, Berenil
      treatment significantly suppressed spontaneous and LPS-induced production of
      inflammatory cytokines by splenic and liver macrophages and significantly
      ameliorated LPS-induced septic shock and the associated cytokine storm.
      CONCLUSIONS/SIGNIFICANCE: Collectively, these results provide evidence that in
      addition to its direct trypanolytic effect, Berenil also modulates the host
      immune response to the parasite in a manner that dampen excessive immune
      activation and production of pathology-promoting pro-inflammatory cytokines,
      suggesting that this drug may also be beneficial for treatment of disease
      conditions caused by excessive production of inflammatory cytokines.

PMID- 23144932
TI  - Summer resource selection and identification of important habitat prior to
      industrial development for the Teshekpuk Caribou Herd in northern Alaska.
AB  - Many caribou (Rangifer tarandus) populations are declining worldwide in part due
      to disturbance from human development. Prior to human development, important
      areas of habitat should be identified to help managers minimize adverse effects.
      Resource selection functions can help identify these areas by providing a link
      between space use and landscape attributes. We estimated resource selection
      during five summer periods at two spatial scales for the Teshekpuk Caribou Herd
      in northern Alaska prior to industrial development to identify areas of high
      predicted use for the herd. Additionally, given the strong influence parturition
      and insect harassment have on space use, we determined how selection differed
      between parturient and non-parturient females, and between periods with and
      without insect harassment. We used location data acquired between 2004-2010 for
      41 female caribou to estimate resource selection functions. Patterns of selection
      varied through summer but caribou consistently avoided patches of flooded
      vegetation and selected areas with a high density of sedge-grass meadow.
      Predicted use by parturient females during calving was almost entirely restricted
      to the area surrounding Teshekpuk Lake presumably due to high concentration of
      sedge-grass meadows, whereas selection for this area by non-parturient females
      was less strong. When insect harassment was low, caribou primarily selected the
      areas around Teshekpuk Lake but when it was high, caribou used areas having
      climates where insect abundance would be lower (i.e., coastal margins, gravel
      bars). Areas with a high probability of use were predominately restricted to the
      area surrounding Teshekpuk Lake except during late summer when high use areas
      were less aggregated because of more general patterns of resource selection.
      Planning is currently underway for establishing where oil and gas development can
      occur in the herd's range, so our results provide land managers with information
      that can help predict and minimize impacts of development on the herd.

PMID- 23144930
TI  - Validation of expression patterns for nine miRNAs in 204 lymph-node negative
      breast cancers.
AB  - INTRODUCTION: Although lymph node negative (LN-) breast cancer patients have a
      good 10-years survival (~85%), most of them still receive adjuvant therapy, while
      only some benefit from this. More accurate prognostication of LN- breast cancer
      patient may reduce over- and under-treatment. Until now proliferation is the
      strongest prognostic factor for LN- breast cancer patients. The small molecule
      microRNA (miRNA) has opened a new window for prognostic markers, therapeutic
      targets and/or therapeutic components. Previously it has been shown that miR
      18a/b, miR-25, miR-29c and miR-106b correlate to high proliferation. METHODS: The
      current study validates nine miRNAs (miR-18a/b miR-25, miR-29c, miR-106b, miR375,
      miR-424, miR-505 and let-7b) significantly correlated with established prognostic
      breast cancer biomarkers. Total RNA was isolated from 204 formaldehyde-fixed
      paraffin embedded (FFPE) LN- breast cancers and analyzed with quantitative real
      time Polymerase Chain Reaction (qPCR). Independent T-test was used to detect
      significant correlation between miRNA expression level and the different
      clinicopathological features for breast cancer. RESULTS: Strong and significant
      associations were observed for high expression of miR-18a/b, miR-106b, miR-25 and
      miR-505 to high proliferation, oestrogen receptor negativity and cytokeratin 5/6
      positivity. High expression of let-7b, miR-29c and miR-375 was detected in more
      differentiated tumours. Kaplan-Meier survival analysis showed that patients with
      high miR-106b expression had an 81% survival rate vs. 95% (P = 0.004) for
      patients with low expression. CONCLUSION: High expression of miR-18a/b are
      strongly associated with basal-like breast cancer features, while miR-106b can
      identify a group with higher risk for developing distant metastases in the
      subgroup of Her2 negatives. Furthermore miR-106b can identify a group of patients
      with 100% survival within the otherwise considered high risk group of patients
      with high proliferation. Using miR-106b as a biomarker in conjunction to mitotic
      activity index could thereby possibly save 18% of the patients with high
      proliferation from overtreatment.

PMID- 23144933
TI  - Self-renewal and pluripotency acquired through somatic reprogramming to human
      cancer stem cells.
AB  - Human induced pluripotent stem cells (iPSCs) are reprogrammed by transient
      expression of transcription factors in somatic cells. Approximately 1% of somatic
      cells can be reprogrammed into iPSCs, while the remaining somatic cells are
      differentially reprogrammed. Here, we established induced pluripotent cancer stem
      like cells (iCSCs) as self-renewing pluripotent cell clones. Stable iCSC lines
      were established from unstable induced epithelial stem cell (iESC) lines through
      re-plating followed by embryoid body formation and serial transplantation. iCSCs
      shared the expression of pluripotent marker genes with iPSCs, except for REX1 and
      LIN28, while exhibited the expression of somatic marker genes EMP1 and PPARgamma.
      iESCs and iCSCs could generate teratomas with high efficiency by implantation
      into immunodeficient mice. The second iCSCs isolated from dissociated cells of
      teratoma from the first iCSCs were stably maintained, showing a gene expression
      profile similar to the first iCSCs. In the first and second iCSCs, transgene
      derived Oct4, Sox2, Klf4, and c-Myc were expressed. Comparative global gene
      expression analyses demonstrated that the first iCSCs were similar to iESCs, and
      clearly different from human iPSCs and somatic cells. In iCSCs, gene expression
      kinetics of the core pluripotency factor and the Myc-related factor were
      pluripotent type, whereas the polycomb complex factor was somatic type. These
      findings indicate that pluripotent tumorigenicity can be conferred on somatic
      cells through up-regulation of the core pluripotency and Myc-related factors,
      prior to establishment of the iPSC molecular network by full reprogramming
      through down-regulation of the polycomb complex factor.

PMID- 23144934
TI  - Micro-RNA30c negatively regulates REDD1 expression in human hematopoietic and
      osteoblast cells after gamma-irradiation.
AB  - We recently demonstrated that a novel cell stress response gene REDD1 protects
      human fetal osteoblast cell line (hFOB) cells from gamma-radiation-induced
      premature senescence. Here we show that levels of endogenous REDD1 are very low
      in human hematopoietic progenitor CD34+ cells regardless of radiation, but highly
      expressed in differentiated hematopoietic cells (14 day cultured CD34+ cells) in
      response to radiation, which might be associated with radiation tolerance of the
      latter cells. To further understand the mechanisms of radiation-induced damage in
      different cells, microRNA (miRNA)-arrays were performed using purified miRNAs
      from CD34+ and hFOB cells before and post-irradiation and real-time reverse
      transcription (RT)-PCR was used to validate the expression profiles of miRNAs in
      the radiation-damaged cells. The results indicate that gamma-radiation
      downregulated 16 miRNAs in CD34+ cells and 14 in hFOB cells. Radiation-induced
      upregulation was observed for 15 miRNAs in CD34+ cells and 18 miRNAs in hFOB
      cells. The profiles of radiation-induced miRNA expression were completely
      different in CD34+ vs. hFOB cells. Radiation up-regulated miRNA (miR)-30b, miR
      30c and miR-30d in CD34+ cells, whereas it inhibited miR-30c expression in hFOB
      cells. Since miR-30 has potential target sites located in the 3'untranslated
      region (UTR) of the REDD1 gene and radiation regulated miR-30c expression in both
      CD34+ and hFOB cells, we further explored the effects of miR-30c on REDD1
      expression using miR-30c inhibitor and precursor (pre-miR-30c). The results show
      that pre-miR-30c transfection suppressed REDD1 expression in 14 day cultured
      CD34+ cells and hFOB cells and resulted in hFOB cell death. In contrast,
      inhibition of miR-30c expression significantly enhanced clonogenicity in CD34+
      cells. Our data suggest that CD34+ and hFOB cells have different miRNA expression
      patterns after irradiation and miR-30c plays a key role in radiation-induced cell
      damage which might be through regulation of REDD1 expression.

PMID- 23144935
TI  - Rapid antigen detection tests for malaria diagnosis in severely ill Papua New
      Guinean children: a comparative study using Bayesian latent class models.
AB  - BACKGROUND: Although rapid diagnostic tests (RDTs) have practical advantages over
      light microscopy (LM) and good sensitivity in severe falciparum malaria in
      Africa, their utility where severe non-falciparum malaria occurs is unknown. LM,
      RDTs and polymerase chain reaction (PCR)-based methods have limitations, and thus
      conventional comparative malaria diagnostic studies employ imperfect gold
      standards. We assessed whether, using Bayesian latent class models (LCMs) which
      do not require a reference method, RDTs could safely direct initial anti
      infective therapy in severe ill children from an area of hyperendemic
      transmission of both Plasmodium falciparum and P. vivax. METHODS AND FINDINGS: We
      studied 797 Papua New Guinean children hospitalized with well-characterized
      severe illness for whom LM, RDT and nested PCR (nPCR) results were available. For
      any severe malaria, the estimated prevalence was 47.5% with RDTs exhibiting
      similar sensitivity and negative predictive value (NPV) to nPCR (>=96.0%). LM was
      the least sensitive test (87.4%) and had the lowest NPV (89.7%), but had the
      highest specificity (99.1%) and positive predictive value (98.9%). For severe
      falciparum malaria (prevalence 42.9%), the findings were similar. For non
      falciparum severe malaria (prevalence 6.9%), no test had the WHO-recommended
      sensitivity and specificity of >95% and >90%, respectively. RDTs were the least
      sensitive (69.6%) and had the lowest NPV (96.7%). CONCLUSIONS: RDTs appear a
      valuable point-of-care test that is at least equivalent to LM in diagnosing
      severe falciparum malaria in this epidemiologic situation. None of the tests had
      the required sensitivity/specificity for severe non-falciparum malaria but the
      number of false-negative RDTs in this group was small.

PMID- 23144937
TI  - A Bayesian interpretation of the particle swarm optimization and its kernel
      extension.
AB  - Particle swarm optimization is a popular method for solving difficult
      optimization problems. There have been attempts to formulate the method in formal
      probabilistic or stochastic terms (e.g. bare bones particle swarm) with the aim
      to achieve more generality and explain the practical behavior of the method. Here
      we present a Bayesian interpretation of the particle swarm optimization. This
      interpretation provides a formal framework for incorporation of prior knowledge
      about the problem that is being solved. Furthermore, it also allows to extend the
      particle optimization method through the use of kernel functions that represent
      the intermediary transformation of the data into a different space where the
      optimization problem is expected to be easier to be resolved-such transformation
      can be seen as a form of prior knowledge about the nature of the optimization
      problem. We derive from the general Bayesian formulation the commonly used
      particle swarm methods as particular cases.

PMID- 23144936
TI  - Different levels of food restriction reveal genotype-specific differences in
      learning a visual discrimination task.
AB  - In behavioural experiments, motivation to learn can be achieved using food
      rewards as positive reinforcement in food-restricted animals. Previous studies
      reduce animal weights to 80-90% of free-feeding body weight as the criterion for
      food restriction. However, effects of different degrees of food restriction on
      task performance have not been assessed. We compared learning task performance in
      mice food-restricted to 80 or 90% body weight (BW). We used adult wildtype (WT;
      C57Bl/6j) and knockout (ephrin-A2-/-) mice, previously shown to have a reverse
      learning deficit. Mice were trained in a two-choice visual discrimination task
      with food reward as positive reinforcement. When mice reached criterion for one
      visual stimulus (80% correct in three consecutive 10 trial sets) they began the
      reverse learning phase, where the rewarded stimulus was switched to the
      previously incorrect stimulus. For the initial learning and reverse phase of the
      task, mice at 90%BW took almost twice as many trials to reach criterion as mice
      at 80%BW. Furthermore, WT 80 and 90%BW groups significantly differed in
      percentage correct responses and learning strategy in the reverse learning phase,
      whereas no differences between weight restriction groups were observed in ephrin
      A2-/- mice. Most importantly, genotype-specific differences in reverse learning
      strategy were only detected in the 80%BW groups. Our results indicate that
      increased food restriction not only results in better performance and a shorter
      training period, but may also be necessary for revealing behavioural differences
      between experimental groups. This has important ethical and animal welfare
      implications when deciding extent of diet restriction in behavioural studies.

PMID- 23144938
TI  - Postnatal ablation of Foxm1 from cardiomyocytes causes late onset cardiac
      hypertrophy and fibrosis without exacerbating pressure overload-induced cardiac
      remodeling.
AB  - Heart disease remains a leading cause of morbidity and mortality in the
      industrialized world. Hypertrophic cardiomyopathy is the most common genetic
      cardiovascular disorder and the most common cause of sudden cardiac death. Foxm1
      transcription factor (also known as HFH-11B, Trident, Win or MPP2) plays an
      important role in the pathogenesis of various cancers and is a critical mediator
      of post-injury repair in multiple organs. Foxm1 has been previously shown to be
      essential for heart development and proliferation of embryonic cardiomyocytes.
      However, the role of Foxm1 in postnatal heart development and in cardiac injury
      has not been evaluated. To delete Foxm1 in postnatal cardiomyocytes, alphaMHC
      Cre/Foxm1(fl/fl) mice were generated. Surprisingly, alphaMHC-Cre/Foxm1(fl/fl)
      mice exhibited normal cardiomyocyte proliferation at postnatal day seven and had
      no defects in cardiac structure or function but developed cardiac hypertrophy and
      fibrosis late in life. The development of cardiomyocyte hypertrophy and cardiac
      fibrosis in aged Foxm1-deficient mice was associated with reduced expression of
      Hey2, an important regulator of cardiac homeostasis, and increased expression of
      genes critical for cardiac remodeling, including MMP9, alphaSMA, fibronectin and
      vimentin. We also found that following aortic constriction Foxm1 mRNA and protein
      were induced in cardiomyocytes. However, Foxm1 deletion did not exacerbate
      cardiac hypertrophy or fibrosis following chronic pressure overload. Our results
      demonstrate that Foxm1 regulates genes critical for age-induced cardiomyocyte
      hypertrophy and cardiac fibrosis.

PMID- 23144939
TI  - In vivo open-bore MRI reveals region- and sub-arc-specific lengthening of the
      unloaded human posterior cruciate ligament.
AB  - Open-bore MRI scanners allow joint soft tissue to be imaged over a large,
      uninterrupted range of flexion. Using an open-bore scanner, 3D para-sagittal
      images of the posterior cruciate ligament (PCL) were collected from seven healthy
      subjects in unloaded, recumbent knee extension and flexion. PCL length was
      measured from one 2D MRI slice partition per flexion angle, per subject. The
      anterior surface of the PCL lengthened significantly between extension and
      flexion (p<0.001). Conversely, the posterior surface did not. Changes were not
      due to the PCL moving relative to the 2D slice partition; measurements made from
      3D reconstructions, which compensated for PCL movement, did not differ
      significantly from measurements made from 2D slice partitions. In a second
      experiment, videos of knee flexion were made by imaging two subjects at several
      flexion angles. Videos allowed soft tissue tracking; examples are included. In a
      third experiment, unloaded knees of seven healthy, recumbent subjects were imaged
      at extension and at 40 degrees , 70 degrees , 90 degrees , 100 degrees , 110
      degrees  and 120 degrees  flexion. The distance between PCL attachments increased
      between extension and 100 degrees , and then decreased (p<0.001). The anterior
      surface of the PCL lengthened over the flexion angles measured (p<0.01). The
      posterior surface of the PCL lengthened between extension and 40 degrees  and
      then shortened (p<0.001). Both attachment separation and anterior surface length
      increased dramatically between extension and 40 degrees , but varied less
      afterwards. Results indicate that PCL dynamics differ between terminal extension
      and active function sub-arcs. Also, attachment separation cannot predict the
      lengthening of all parts of the PCL, nor can lengthening of one part of the PCL
      predict the lengthening of another part. A potential connection between
      lengthening and loading is discussed. We conclude that low-field MRI can assess
      ligament lengthening during flexion, and that the dynamics of the PCL for any
      given region and sub-arc should be measured directly.

PMID- 23144940
TI  - Effect of aging and dietary salt and potassium intake on endothelial PTEN
      (Phosphatase and tensin homolog on chromosome 10) function.
AB  - Aging promotes endothelial dysfunction, defined as a reduction in bioavailable
      nitric oxide (NO) produced by the endothelial isoform of nitric oxide synthase
      (NOS3). This enzyme is critically regulated by phosphorylation by protein kinase
      B (Akt), which in turn is regulated by the lipid phosphatase, PTEN. The present
      series of studies demonstrated a reduction in bioavailable NO as the age of rats
      increased from 1 to 12 months. At 12 months of age, rats no longer demonstrated
      increases in phosphorylated NOS3 in response to high dietary salt intake.
      Endothelial cell levels of PTEN increased with age and became refractory to
      change with increased salt intake. In contrast to the reduction in NO production,
      endothelial cell production of transforming growth factor-beta (TGF-beta)
      relative to NO increased progressively with age. In macrovascular endothelial
      cells, PTEN was regulated in a dose-dependent fashion by TGF-beta, which was
      further regulated by extracellular [KCl]. When combined with prior studies, the
      present series of experiments suggested an integral role for PTEN in endothelial
      cell pathobiology of aging and an important mitigating function of TGF-beta in
      endothelial PTEN regulation. The findings further supported a role for diet in
      affecting vascular function through the production of TGF-beta and NO.

PMID- 23144941
TI  - Prevalence and characteristics associated with malnutrition at hospitalization
      among patients with acquired immunodeficiency syndrome in Brazil.
AB  - BACKGROUND: Brazil's National STD/AIDS Program is considered a model of success
      worldwide. However, AIDS-associated malnutrition continues in subgroups of
      Brazilian patients despite access to free highly active antiretroviral therapy
      (HAART). We aimed to identify the prevalence of malnutrition and associated
      factors among patients hospitalized with AIDS. METHODS: We conducted a cross
      sectional nutritional assessment among 127 adults hospitalized with AIDS in
      Brazil's third largest city. Using anthropometric measurements, we determined the
      prevalence of malnutrition (body mass index <18.5 kg/m2) at hospitalization.
      Prevalence ratios of malnutrition by demographic, socioeconomic, and clinical
      conditions were estimated using log-binomial regression. RESULTS: One-third of
      participants were first informed of their HIV disease during the current
      hospitalization and recent treatment interruption was common (71%) among those on
      HAART. Forty-three percent were malnourished and 35% had severe weight loss at
      admission. Patient characteristics independently associated with malnutrition
      were older age (2% increased prevalence for each year; 95% confidence interval
      [CI] 0-4%) and very low daily per capita household income. Living on <USD 2.00,
      USD 2.00-4.99 or USD 5.00-9.99 increased the prevalence of malnutrition by 2.01
      (95% CI 1.06-3.81), 1.75 (95% CI 0.92-3.35) and 1.42 (95% CI 0.76-2.65) times,
      respectively, compared to >=USD 10.00 per day. Chronic diarrhea was marginally
      associated with malnutrition (RR 1.42; 95% CI 0.99-2.04). Overall, 16% of the
      patients died during hospitalization. We observed a trend toward higher in
      hospital case fatality among malnourished patients (22% vs. 12% for patients with
      and without malnutrition, respectively; chi square P = 0.14). CONCLUSIONS:
      Unacceptably high rates of malnutrition persist in Brazilians hospitalized with
      AIDS and our results reinforce the importance of nutritional evaluations in these
      patients. Improved early testing and treatment adherence strategies may continue
      to help reduce AIDS-related morbidity and mortality in Brazil, yet novel
      interventions to disrupt the cycle of poverty, HIV, and malnutrition are also
      urgently needed.

PMID- 23144942
TI  - Feeding-based RNA interference of a gap gene is lethal to the pea aphid,
      Acyrthosiphon pisum.
AB  - The gap gene hunchback (hb) is a key regulator in the anteroposterior patterning
      of insects. Loss-of-function of hb resulted in segmentation defects in the next
      generation. In this paper, hb expression level was investigated at different
      developmental stages of the pea aphid, Acyrthosiphon pisum (Ap). Aphb mRNA was
      most early detected at the first instar stage and showed an incontinuous increase
      in the whole life cycle. Ingested RNA interference was performed at the second
      instar stage to knockdown the Aphb expression. Continuous feeding of Aphb double
      stranded RNA mixed in artificial diet led to reduction of Aphb transcripts and
      rise of insect lethality. These results indicated that hunchback was a good RNAi
      target in the management of insect pests.

PMID- 23144943
TI  - The TSC1/2 complex controls Drosophila pigmentation through TORC1-dependent
      regulation of catecholamine biosynthesis.
AB  - In Drosophila, the pattern of adult pigmentation is initiated during late pupal
      stages by the production of catecholamines DOPA and dopamine, which are converted
      to melanin. The pattern and degree of melanin deposition is controlled by the
      expression of genes such as ebony and yellow as well as by the enzymes involved
      in catecholamine biosynthesis. In this study, we show that the conserved
      TSC/TORC1 cell growth pathway controls catecholamine biosynthesis in Drosophila
      during pigmentation. We find that high levels of Rheb, an activator of the TORC1
      complex, promote premature pigmentation in the mechanosensory bristles during
      pupal stages, and alter pigmentation in the cuticle of the adult fly. Disrupting
      either melanin synthesis by RNAi knockdown of melanogenic enzymes such as
      tyrosine hydroxylase (TH), or downregulating TORC1 activity by Raptor knockdown,
      suppresses the Rheb-dependent pigmentation phenotype in vivo. Increased Rheb
      activity drives pigmentation by increasing levels of TH in epidermal cells. Our
      findings indicate that control of pigmentation is linked to the cellular nutrient
      sensing pathway by regulating levels of a critical enzyme in melanogenesis,
      providing further evidence that inappropriate activation of TORC1, a hallmark of
      the human tuberous sclerosis complex tumor syndrome disorder, can alter metabolic
      and differentiation pathways in unexpected ways.

PMID- 23144944
TI  - Dynamic proteomics of human protein level and localization across the cell cycle.
AB  - Regulation of proteins across the cell cycle is a basic process in cell biology.
      It has been difficult to study this globally in human cells due to lack of
      methods to accurately follow protein levels and localizations over time.
      Estimates based on global mRNA measurements suggest that only a few percent of
      human genes have cell-cycle dependent mRNA levels. Here, we used dynamic
      proteomics to study the cell-cycle dependence of proteins. We used 495 clones of
      a human cell line, each with a different protein tagged fluorescently at its
      endogenous locus. Protein level and localization was quantified in individual
      cells over 24h of growth using time-lapse microscopy. Instead of standard
      chemical or mechanical methods for cell synchronization, we employed in-silico
      synchronization to place protein levels and localization on a time axis between
      two cell divisions. This non-perturbative synchronization approach, together with
      the high accuracy of the measurements, allowed a sensitive assay of cell-cycle
      dependence. We further developed a computational approach that uses texture
      features to evaluate changes in protein localizations. We find that 40% of the
      proteins showed cell cycle dependence, of which 11% showed changes in protein
      level and 35% in localization. This suggests that a broader range of cell-cycle
      dependent proteins exists in human cells than was previously appreciated. Most of
      the cell-cycle dependent proteins exhibit changes in cellular localization. Such
      changes can be a useful tool in the regulation of the cell-cycle being fast and
      efficient.

PMID- 23144946
TI  - The determinants of HIV treatment costs in resource limited settings.
AB  - BACKGROUND: Governments and international donors have partnered to provide free
      HIV treatment to over 6 million individuals in low and middle-income countries.
      Understanding the determinants of HIV treatment costs will help improve
      efficiency and provide greater certainty about future resource needs. METHODS AND
      FINDINGS: We collected data on HIV treatment costs from 54 clinical sites in
      Botswana, Ethiopia, Mozambique, Nigeria, Uganda, and Vietnam. Sites provided free
      HIV treatment funded by the U.S. President's Emergency Plan for AIDS Relief
      (PEPFAR), national governments, and other partners. Service delivery costs were
      categorized into successive six-month periods from the date when each site began
      HIV treatment scale-up. A generalized linear mixed model was used to investigate
      relationships between site characteristics and per-patient costs, excluding ARV
      expenses. With predictors at their mean values, average annual per-patient costs
      were $177 (95% CI: 127-235) for pre-ART patients, $353 (255-468) for adult
      patients in the first 6 months of ART, and $222 (161-296) for adult patients on
      ART for >6 months (excludes ARV costs). Patient volume (no. patients receiving
      treatment) and site maturity (months since clinic began providing treatment
      services) were both strong independent predictors of per-patient costs.
      Controlling for other factors, costs declined by 43% (18-63) as patient volume
      increased from 500 to 5,000 patients, and by 28% (6-47) from 5,000 to 10,000
      patients. For site maturity, costs dropped 41% (28-52) between months 0-12 and
      25% (15-35) between months 12-24. Price levels (proxied by per-capita GDP) were
      also influential, with costs increasing by 22% (4-41) for each doubling in per
      capita GDP. Additionally, the frequency of clinical follow-up, frequency of
      laboratory monitoring, and clinician-patient ratio were significant independent
      predictors of per-patient costs. CONCLUSIONS: Substantial reductions in per
      patient service delivery costs occur as sites mature and patient cohorts increase
      in size. Other predictors suggest possible strategies to reduce per-patient
      costs.

PMID- 23144945
TI  - Identification of ATP-binding regions in the RyR1 Ca2+ release channel.
AB  - ATP is an important modulator of gating in type 1 ryanodine receptor (RyR1), also
      known as a Ca2+ release channel in skeletal muscle cells. The activating effect
      of ATP on this channel is achieved by directly binding to one or more sites on
      the RyR1 protein. However, the number and location of these sites have yet to be
      determined. To identify the ATP-binding regions within RyR1 we used 2N3ATP-2',3'
      Biotin-LC-Hydrazone (BioATP-HDZ), a photo-reactive ATP analog to covalently label
      the channel. We found that BioATP-HDZ binds RyR1 specifically with an IC50 =
      0.6+/-0.2 mM, comparable with the reported EC50 for activation of RyR1 with ATP.
      Controlled proteolysis of labeled RyR1 followed by sequence analysis revealed
      three fragments with apparent molecular masses of 95, 45 and 70 kDa that were
      crosslinked by BioATP-HDZ and identified as RyR1 sequences. Our analysis
      identified four glycine-rich consensus motifs that can potentially constitute ATP
      binding sites and are located within the N-terminal 95-kDa fragment. These
      putative nucleotide-binding sequences include amino acids 699-704, 701-706, 1081
      1084 and 1195-1200, which are conserved among the three RyR isoforms. Located
      next to the N-terminal disease hotspot region in RyR1, these sequences may
      communicate the effects of ATP-binding to channel function by tuning
      conformational motions within the neighboring cytoplasmic regulatory domains. Two
      other labeled fragments lack ATP-binding consensus motifs and may form non
      canonical ATP-binding sites. Based on domain topology in the 3D structure of RyR1
      it is also conceivable that the identified ATP-binding regions, despite their
      wide separation in the primary sequence, may actually constitute the same non
      contiguous ATP-binding pocket within the channel tetramer.

PMID- 23144947
TI  - CXCL10 is critical for the generation of protective CD8 T cell response induced
      by antigen pulsed CpG-ODN activated dendritic cells.
AB  - The visceral form of leishmaniasis is the most severe form of the disease and of
      particular concern due to the emerging problem of HIV/visceral leishmaniasis (VL)
      co-infection in the tropics. Till date miltefosine, amphotericin B and
      pentavalent antimony compounds remain the main treatment regimens for
      leishmaniasis. However, because of severe side effects, there is an urgent need
      for alternative improved therapies to combat this dreaded disease. In the present
      study, we have used the murine model of leishmaniasis to evaluate the potential
      role played by soluble leishmanial antigen (SLA) pulsed-CpG-ODN stimulated
      dendritic cells (SLA-CpG-DCs) in restricting the intracellular leishmanial
      growth. We found that mice vaccinated with a single dose of SLA-pulsed DC
      stimulated by CpG-ODN were protected against a subsequent leishmanial challenge
      and had a dramatic reduction in parasite burden along with the generation of
      parasite specific cytotoxic T lymphocytes. Moreover, we demonstrate that the
      induction of protective immunity conferred by SLA-CpG-DCs depends entirely on the
      CXC chemokine IFN-gamma-inducible protein 10 (CXCL10; IP-10). CXCL10 is directly
      involved in the generation of a parasite specific CD8+ T cell-mediated immune
      response. We observed significant reduction of CD8+ T cells in mice depleted of
      CXCL10 suggesting a direct role of CXCL10 in the generation of CD8+ T cells in
      SLA-CpG-DCs vaccinated mice. CXCL10 also contributed towards the generation of
      perforin and granzyme B, two important cytolytic mediators of CD8+ T cells,
      following SLA-CpG-DCs vaccination. Together, these findings strongly demonstrate
      that CXCL10 is critical for rendering a protective cellular immunity during SLA
      CpG-DC vaccination that confers protection against Leishmania donovani infection.

PMID- 23144948
TI  - Avian adeno-associated virus vector efficiently transduces neurons in the
      embryonic and post-embryonic chicken brain.
AB  - The domestic chicken is an attractive model system to explore the development and
      function of brain circuits. Electroporation-mediated and retrovirus (including
      lentivirus) vector-mediated gene transfer techniques have been widely used to
      introduce genetic material into chicken cells. However, it is still challenging
      to efficiently transduce chicken postmitotic neurons without harming the cells.
      To overcome this problem, we searched for a virus vector suitable for gene
      transfer into chicken neurons, and report here a novel recombinant virus vector
      derived from avian adeno-associated virus (A3V). A3V vector efficiently
      transduces neuronal cells, but not non-neuronal cells in the brain. A single A3V
      injection into a postembryonic chick brain allows gene expression selectively in
      neuronal cells within 24 hrs. Such rapid and neuron-specific gene transduction
      raises the possibility that A3V vector can be utilized for studies of memory
      formation in filial imprinting, which occurs during the early postnatal days. A3V
      injection into the neural tube near the ear vesicle at early embryonic stage
      resulted in persistent and robust gene expression until E20.5 in the auditory
      brainstem. We further devised an A3V-mediated tetracycline (Tet) dependent gene
      expression system as a tool for studying the auditory circuit, consisting of the
      nucleus magnocellularis (NM) and nucleus laminaris (NL), that primarily computes
      interaural time differences (ITDs). Using this Tet system, we can transduce NM
      neurons without affecting NL neurons. Thus, the A3V technology complements
      current gene transfer techniques in chicken studies and will contribute to better
      understanding of the functional organization of neural circuits.

PMID- 23144949
TI  - Genome-wide identification of copy number variations in Chinese Holstein.
AB  - Recent studies of mammalian genomes have uncovered the vast extent of copy number
      variations (CNVs) that contribute to phenotypic diversity. Compared to SNP, a CNV
      can cover a wider chromosome region, which may potentially incur substantial
      sequence changes and induce more significant effects on phenotypes. CNV has been
      becoming an alternative promising genetic marker in the field of genetic
      analyses. Here we firstly report an account of CNV regions in the cattle genome
      in Chinese Holstein population. The Illumina Bovine SNP50K Beadchips were used
      for screening 2047 Holstein individuals. Three different programes (PennCNV,
      cnvPartition and GADA) were implemented to detect potential CNVs. After a strict
      CNV calling pipeline, a total of 99 CNV regions were identified in cattle genome.
      These CNV regions cover 23.24 Mb in total with an average size of 151.69 Kb. 52
      out of these CNV regions have frequencies of above 1%. 51 out of these CNV
      regions completely or partially overlap with 138 cattle genes, which are
      significantly enriched for specific biological functions, such as signaling
      pathway, sensory perception response and cellular processes. The results provide
      valuable information for constructing a more comprehensive CNV map in the cattle
      genome and offer an important resource for investigation of genome structure and
      genomic variation underlying traits of interest in cattle.

PMID- 23144951
TI  - Between-group variation in female dispersal, kin composition of groups, and
      proximity patterns in a black-and-white colobus monkey (Colobus vellerosus).
AB  - A growing body of evidence shows within-population variation in natal dispersal,
      but the effects of such variation on social relationships and the kin composition
      of groups remain poorly understood. We investigate the link between dispersal,
      the kin composition of groups, and proximity patterns in a population of black
      and-white colobus (Colobus vellerosus) that shows variation in female dispersal.
      From 2006 to 2011, we collected behavioral data, demographic data, and fecal
      samples of 77 males and 92 females residing in eight groups at Boabeng-Fiema,
      Ghana. A combination of demographic data and a genetic network analysis showed
      that although philopatry was female-biased, only about half of the females
      resided in their natal groups. Only one group contained female-female dyads with
      higher average relatedness than randomly drawn animals of both sexes from the
      same group. Despite between-group variation in female dispersal and kin
      composition, female-female dyads in most of the study groups had higher proximity
      scores than randomly drawn dyads from the same group. We conclude that groups
      fall along a continuum from female dispersed, not kin-based, and not bonded to
      female philopatric, kin-based, and bonded. We found only partial support for the
      predicted link between dispersal, kin composition, and social relationships. In
      contrast to most mammals where the kin composition of groups is a good predictor
      of the quality of female-female relationships, this study provides further
      support for the notion that kinship is not necessary for the development and
      maintenance of social bonds in some gregarious species.

PMID- 23144950
TI  - Tmod1 and CP49 synergize to control the fiber cell geometry, transparency, and
      mechanical stiffness of the mouse lens.
AB  - The basis for mammalian lens fiber cell organization, transparency, and
      biomechanical properties has contributions from two specialized cytoskeletal
      systems: the spectrin-actin membrane skeleton and beaded filament cytoskeleton.
      The spectrin-actin membrane skeleton predominantly consists of alpha2beta2
      spectrin strands interconnecting short, tropomyosin-coated actin filaments, which
      are stabilized by pointed-end capping by tropomodulin 1 (Tmod1) and structurally
      disrupted in the absence of Tmod1. The beaded filament cytoskeleton consists of
      the intermediate filament proteins CP49 and filensin, which require CP49 for
      assembly and contribute to lens transparency and biomechanics. To assess the
      simultaneous physiological contributions of these cytoskeletal networks and
      uncover potential functional synergy between them, we subjected lenses from mice
      lacking Tmod1, CP49, or both to a battery of structural and physiological assays
      to analyze fiber cell disorder, light scattering, and compressive biomechanical
      properties. Findings show that deletion of Tmod1 and/or CP49 increases lens fiber
      cell disorder and light scattering while impairing compressive load-bearing, with
      the double mutant exhibiting a distinct phenotype compared to either single
      mutant. Moreover, Tmod1 is in a protein complex with CP49 and filensin,
      indicating that the spectrin-actin network and beaded filament cytoskeleton are
      biochemically linked. These experiments reveal that the spectrin-actin membrane
      skeleton and beaded filament cytoskeleton establish a novel functional synergy
      critical for regulating lens fiber cell geometry, transparency, and mechanical
      stiffness.

PMID- 23144952
TI  - New insights into the Hendra virus attachment and entry process from structures
      of the virus G glycoprotein and its complex with Ephrin-B2.
AB  - Hendra virus and Nipah virus, comprising the genus Henipavirus, are recently
      emerged, highly pathogenic and often lethal zoonotic agents against which there
      are no approved therapeutics. Two surface glycoproteins, the attachment (G) and
      fusion (F), mediate host cell entry. The crystal structures of the Hendra G
      glycoprotein alone and in complex with the ephrin-B2 receptor reveal that
      henipavirus uses Tryptophan 122 on ephrin-B2/B3 as a "latch" to facilitate the G
      receptor association. Structural-based mutagenesis of residues in the Hendra G
      glycoprotein at the receptor binding interface document their importance for
      viral attachments and entry, and suggest that the stability of the Hendra-G
      ephrin attachment complex does not strongly correlate with the efficiency of
      viral entry. In addition, our data indicates that conformational rearrangements
      of the G glycoprotein head domain upon receptor binding may be the trigger
      leading to the activation of the viral F fusion glycoprotein during virus
      infection.

PMID- 23144953
TI  - Molecular epidemiology of human immunodeficiency virus type 1 in Guangdong
      province of southern China.
AB  - BACKGROUND: Although the outbreak of human immunodeficiency virus type 1 (HIV-1)
      in Guangdong has been documented for more than a decade, the molecular
      characteristics of such a regional HIV-1 epidemic remained unknown.
      METHODOLOGY/PRINCIPAL FINDINGS: By sequencing of HIV-1 pol/env genes and
      phylogenetic analysis, we performed a molecular epidemiologic study in a
      representative subset (n  = 200) of the 508 HIV-1-seropositive individuals
      followed up at the center for HIV/AIDS care and treatment of Guangzhou Hospital
      of Infectious Diseases. Of 157 samples (54.1% heterosexual acquired adults, 20.4%
      needle-sharing drug users, 5.7% receivers of blood transfusion, 1.3% men who have
      sex with men, and 18.5% remained unknown) with successful sequencing for both pol
      and env genes, 105 (66.9%) HIV-1 subtype CRF01_AE and 24 (15.3%) CRF07_BC, 9
      (5.7%) B', 5 (3.2%) CRF08_BC, 5 (3.2%) B, 1 (0.6%) C, 3 (1.9%) CRF02_AG, and 5
      (3.2%) inter-region recombinants were identified within pol/env sequences.
      Thirteen (8.3%) samples (3 naives, 6 and 5 received with antiretroviral treatment
      [ART] 1-21 weeks and >=24 weeks respectively) showed mutations conferring
      resistance to nucleoside/nonnucleoside reverse transcriptase inhibitors or
      protease inhibitors. Among 63 ART-naive patients, 3 (4.8%) showed single or
      multiple drug resistant mutations. Phylogenetic analysis showed 8 small clusters
      (2-3 sequences/cluster) with only 17 (10.8%) sequences involved.
      CONCLUSION/SIGNIFICANCE: This study confirms that sexual transmission with
      dominant CRF01_AE strain is a major risk for current HIV-1 outbreak in the
      Guangdong's general population. The transmission with drug-resistant variants is
      starting to emerge in this region.

PMID- 23144954
TI  - Immunization with a hemagglutinin-derived synthetic peptide formulated with a CpG
      DNA-liposome complex induced protection against lethal influenza virus infection
      in mice.
AB  - Whole-virus vaccines, including inactivated or live-attenuated influenza
      vaccines, have been conventionally developed and supported as a prophylaxis.
      These currently available virus-based influenza vaccines are widely used in the
      clinic, but the vaccine production takes a long time and a huge number of
      embryonated chicken eggs. To overcome the imperfection of egg-based influenza
      vaccines, epitope-based peptide vaccines have been studied as an alternative
      approach. Here, we formulated an efficacious peptide vaccine without carriers
      using phosphodiester CpG-DNA and a special liposome complex. Potential epitope
      peptides predicted from the hemagglutinin (HA) protein of the H5N1 A/Viet
      Nam/1203/2004 strain (NCBI database, AAW80717) were used to immunize mice along
      with phosphodiester CpG-DNA co-encapsulated in a phosphatidyl-beta-oleoyl-gamma
      palmitoyl ethanolamine (DOPE):cholesterol hemisuccinate (CHEMS) complex
      (Lipoplex(O)) without carriers. We identified a B cell epitope peptide (hH5N1
      HA233 epitope, 14 amino acids) that can potently induce epitope-specific
      antibodies. Furthermore, immunization with a complex of the B cell epitope and
      Lipoplex(O) completely protects mice challenged with a lethal dose of recombinant
      H5N1 virus. These results suggest that our improved peptide vaccine technology
      can be promptly applied to vaccine development against pandemic influenza.
      Furthermore our results suggest that potent epitopes, which cannot be easily
      found using proteins or a virus as an antigen, can be screened when we use a
      complex of peptide epitopes and Lipoplex(O).

PMID- 23144956
TI  - Using routinely reported tuberculosis genotyping and surveillance data to predict
      tuberculosis outbreaks.
AB  - We combined routinely reported tuberculosis (TB) patient characteristics with
      genotyping data and measures of geospatial concentration to predict which small
      clusters (i.e., consisting of only 3 TB patients) in the United States were most
      likely to become outbreaks of at least 6 TB cases. Of 146 clusters analyzed, 16
      (11.0%) grew into outbreaks. Clusters most likely to become outbreaks were those
      in which at least 1 of the first 3 patients reported homelessness or excess
      alcohol or illicit drug use or was incarcerated at the time of TB diagnosis and
      in which the cluster grew rapidly (i.e., the third case was diagnosed within 5.3
      months of the first case). Of 17 clusters with these characteristics and
      therefore considered high risk, 9 (53%) became outbreaks. This retrospective
      cohort analysis of clusters in the United States suggests that routinely reported
      data may identify small clusters that are likely to become outbreaks and which
      are therefore candidates for intensified contact investigations.

PMID- 23144955
TI  - Transcriptional alterations related to neuropathology and clinical manifestation
      of Alzheimer's disease.
AB  - Alzheimer's disease (AD) is the most common cause of dementia in the human
      population, characterized by a spectrum of neuropathological abnormalities that
      results in memory impairment and loss of other cognitive processes as well as the
      presence of non-cognitive symptoms. Transcriptomic analyses provide an important
      approach to elucidating the pathogenesis of complex diseases like AD, helping to
      figure out both pre-clinical markers to identify susceptible patients and the
      early pathogenic mechanisms to serve as therapeutic targets. This study provides
      the gene expression profile of postmortem brain tissue from subjects with clinic
      pathological AD (Braak IV, V, or V and CERAD B or C; and CDR >=1), preclinical AD
      (Braak IV, V, or VI and CERAD B or C; and CDR = 0), and healthy older individuals
      (Braak <= II and CERAD 0 or A; and CDR = 0) in order to establish genes related
      to both AD neuropathology and clinical emergence of dementia. Based on
      differential gene expression, hierarchical clustering and network analysis, genes
      involved in energy metabolism, oxidative stress, DNA damage/repair, senescence,
      and transcriptional regulation were implicated with the neuropathology of AD; a
      transcriptional profile related to clinical manifestation of AD could not be
      detected with reliability using differential gene expression analysis, although
      genes involved in synaptic plasticity, and cell cycle seems to have a role
      revealed by gene classifier. In conclusion, the present data suggest gene
      expression profile changes secondary to the development of AD-related pathology
      and some genes that appear to be related to the clinical manifestation of
      dementia in subjects with significant AD pathology, making necessary further
      investigations to better understand these transcriptional findings on the
      pathogenesis and clinical emergence of AD.

PMID- 23144957
TI  - Late maturation of adult-born neurons in the temporal dentate gyrus.
AB  - Hippocampal function varies along its septotemporal axis, with the septal
      (dorsal) pole more frequently involved in spatial learning and memory and the
      temporal (ventral) pole playing a greater role in emotional behaviors. One
      feature that varies across these subregions is adult neurogenesis. New neurons
      are more numerous in the septal hippocampus but are more active in the temporal
      hippocampus during water maze training. However, many other aspects of adult
      neurogenesis remain unexplored in the context of septal versus temporal
      subregions. In addition, the dentate gyrus contains another functionally
      important anatomical division along the transverse axis, with the suprapyramidal
      blade showing greater experience-related activity than the infrapyramidal blade.
      Here we ask whether new neurons differ in their rates of survival and maturation
      along the septotemporal and transverse axes. We found that neurogenesis is
      initially higher in the infrapyramidal than suprapyramidal blade, but these cells
      are less likely to survive, resulting in similar densities of neurons in the two
      blades by four weeks. Across the septotemporal axis, neurogenesis was higher in
      septal than temporal pole, while the survival rate of new neurons did not differ.
      Maturation was assessed by immunostaining for the neuronal marker, NeuN, which
      increases in expression level with maturation, and for the immediate-early gene,
      Arc, which suggests a neuron is capable of undergoing activity-dependent synaptic
      plasticity. Maturation occurred approximately 1-2 weeks earlier in the septal
      pole than in the temporal pole. This suggests that septal neurons may contribute
      to function sooner; however, the prolonged maturation of new temporal neurons may
      endow them with a longer window of plasticity during which their functions could
      be distinct from those of the mature granule cell population. These data point to
      subregional differences in new neuron maturation and suggest that changes in
      neurogenesis could alter different hippocampus-dependent behaviors with different
      time courses.

PMID- 23144958
TI  - Readmissions and death after ICU discharge: development and validation of two
      predictive models.
AB  - INTRODUCTION: Early discharge from the ICU is desirable because it shortens time
      in the ICU and reduces care costs, but can also increase the likelihood of ICU
      readmission and post-discharge unanticipated death if patients are discharged
      before they are stable. We postulated that, using eICU(r) Research Institute
      (eRI) data from >400 ICUs, we could develop robust models predictive of post
      discharge death and readmission that may be incorporated into future clinical
      information systems (CIS) to assist ICU discharge planning. METHODS:
      Retrospective, multi-center, exploratory cohort study of ICU survivors within the
      eRI database between 1/1/2007 and 3/31/2011. EXCLUSION CRITERIA: DNR or care
      limitations at ICU discharge and discharge to location external to hospital.
      Patients were randomized (2?1) to development and validation cohorts.
      Multivariable logistic regression was performed on a broad range of variables
      including: patient demographics, ICU admission diagnosis, admission severity of
      illness, laboratory values and physiologic variables present during the last 24
      hours of the ICU stay. Multiple imputation was used to address missing data. The
      primary outcomes were the area under the receiver operator characteristic curves
      (auROC) in the validation cohorts for the models predicting readmission and death
      within 48 hours of ICU discharge. RESULTS: 469,976 and 234,987 patients
      representing 219 hospitals were in the development and validation cohorts. Early
      ICU readmission and death was experienced by 2.54% and 0.92% of all patients,
      respectively. The relationship between predictors and outcomes (death vs
      readmission) differed, justifying the need for separate models. The models for
      early readmission and death produced auROCs of 0.71 and 0.92, respectively. Both
      models calibrated well across risk groups. CONCLUSIONS: Our models for death and
      readmission after ICU discharge showed good to excellent discrimination and good
      calibration. Although prospective validation is warranted, we speculate that
      these models may have value in assisting clinicians with ICU discharge planning.

PMID- 23144959
TI  - The fixation and saccade P3.
AB  - Although most instances of object recognition during natural viewing occur in the
      presence of saccades, the neural correlates of objection recognition have almost
      exclusively been examined during fixation. Recent studies have indicated that
      there are post-saccadic modulations of neural activity immediately following eye
      movement landing; however, whether post-saccadic modulations affect relatively
      late occurring cognitive components such as the P3 has not been explored. The P3
      as conventionally measured at fixation is commonly used in brain computer
      interfaces, hence characterizing the post-saccadic P3 could aid in the
      development of improved brain computer interfaces that allow for eye movements.
      In this study, the P3 observed after saccadic landing was compared to the P3
      measured at fixation. No significant differences in P3 start time, temporal
      persistence, or amplitude were found between fixation and saccade trials.
      Importantly, sensory neural responses canceled in the target minus distracter
      comparisons used to identify the P3. Our results indicate that relatively late
      occurring cognitive neural components such as the P3 are likely less sensitive to
      post saccadic modulations than sensory neural components and other neural
      activity occurring shortly after eye movement landing. Furthermore, due to the
      similarity of the fixation and saccade P3, we conclude that the P3 following
      saccadic landing could possibly be used as a viable signal in brain computer
      interfaces allowing for eye movements.

PMID- 23144961
TI  - Testing pairwise association between spatially autocorrelated variables: a new
      approach using surrogate lattice data.
AB  - BACKGROUND: Independence between observations is a standard prerequisite of
      traditional statistical tests of association. This condition is, however,
      violated when autocorrelation is present within the data. In the case of
      variables that are regularly sampled in space (i.e. lattice data or images), such
      as those provided by remote-sensing or geographical databases, this problem is
      particularly acute. Because analytic derivation of the null probability
      distribution of the test statistic (e.g. Pearson's r) is not always possible when
      autocorrelation is present, we propose instead the use of a Monte Carlo
      simulation with surrogate data. METHODOLOGY/PRINCIPAL FINDINGS: The null
      hypothesis that two observed mapped variables are the result of independent
      pattern generating processes is tested here by generating sets of random image
      data while preserving the autocorrelation function of the original images.
      Surrogates are generated by matching the dual-tree complex wavelet spectra (and
      hence the autocorrelation functions) of white noise images with the spectra of
      the original images. The generated images can then be used to build the
      probability distribution function of any statistic of association under the null
      hypothesis. We demonstrate the validity of a statistical test of association
      based on these surrogates with both actual and synthetic data and compare it with
      a corrected parametric test and three existing methods that generate surrogates
      (randomization, random rotations and shifts, and iterative amplitude adjusted
      Fourier transform). Type I error control was excellent, even with strong and long
      range autocorrelation, which is not the case for alternative methods.
      CONCLUSIONS/SIGNIFICANCE: The wavelet-based surrogates are particularly
      appropriate in cases where autocorrelation appears at all scales or is direction
      dependent (anisotropy). We explore the potential of the method for association
      tests involving a lattice of binary data and discuss its potential for validation
      of species distribution models. An implementation of the method in Java for the
      generation of wavelet-based surrogates is available online as supporting
      material.

PMID- 23144962
TI  - High precision u/th dating of first Polynesian settlement.
AB  - Previous studies document Nukuleka in the Kingdom of Tonga as a founder colony
      for first settlement of Polynesia by Lapita peoples. A limited number of
      radiocarbon dates are one line of evidence supporting this claim, but they cannot
      precisely establish when this event occurred, nor can they afford a detailed
      chronology for sequent occupation. High precision U/Th dates of Acropora coral
      files (abraders) from Nukuleka give unprecedented resolution, identifying the
      founder event by 2838+/-8 BP and documenting site development over the ensuing
      250 years. The potential for dating error due to post depositional diagenetic
      alteration of ancient corals at Nukuleka also is addressed through sample
      preparation protocols and paired dates on spatially separated samples for
      individual specimens. Acropora coral files are widely distributed in Lapita sites
      across Oceania. U/Th dating of these artifacts provides unparalleled
      opportunities for greater precision and insight into the speed and timing of this
      final chapter in human settlement of the globe.

PMID- 23144960
TI  - Urotensin II in invertebrates: from structure to function in Aplysia californica.
AB  - Neuropeptides are ancient signaling molecules that are involved in many aspects
      of organism homeostasis and function. Urotensin II (UII), a peptide with a range
      of hormonal functions, previously has been reported exclusively in vertebrates.
      Here, we provide the first direct evidence that UII-like peptides are also
      present in an invertebrate, specifically, the marine mollusk Aplysia californica.
      The presence of UII in the central nervous system (CNS) of Aplysia implies a more
      ancient gene lineage than vertebrates. Using representational difference
      analysis, we identified an mRNA of a protein precursor that encodes a predicted
      neuropeptide, we named Aplysia urotensin II (apUII), with a sequence and
      structural similarity to vertebrate UII. With in-situ hybridization and
      immunohistochemistry, we mapped the expression of apUII mRNA and its prohormone
      in the CNS and localized apUII-like immunoreactivity to buccal sensory neurons
      and cerebral A-cluster neurons. Mass spectrometry performed on individual
      isolated neurons, and tandem mass spectrometry on fractionated peptide extracts,
      allowed us to define the posttranslational processing of the apUII neuropeptide
      precursor and confirm the highly conserved cyclic nature of the mature
      neuropeptide apUII. Electrophysiological analysis of the central effects of a
      synthetic apUII suggests it plays a role in satiety and/or aversive signaling in
      feeding behaviors. Finding the homologue of vertebrate UII in the numerically
      small CNS of an invertebrate animal model is important for gaining insights into
      the molecular mechanisms and pathways mediating the bioactivity of UII in the
      higher metazoan.

PMID- 23144963
TI  - Effects of growth and mutation on pattern formation in tissues.
AB  - In many developing tissues, neighboring cells enter different developmental
      pathways, resulting in a fine-grained pattern of different cell states. The most
      common mechanism that generates such patterns is lateral inhibition, for example
      through Delta-Notch coupling. In this work, we simulate growth of tissues
      consisting of a hexagonal arrangement of cells laterally inhibiting their
      neighbors. We find that tissue growth by cell division and cell migration tends
      to produce ordered patterns, whereas lateral growth leads to disordered, patchy
      patterns. Ordered patterns are very robust to mutations (gene silencing or
      activation) in single cells. In contrast, mutation in a cell of a disordered
      tissue can produce a larger and more widespread perturbation of the pattern. In
      tissues where ordered and disordered patches coexist, the perturbations spread
      mostly at boundaries between patches. If cell division occurs on time scales
      faster than the degradation time, disordered patches will appear. Our work
      suggests that careful experimental characterization of the disorder in tissues
      could pinpoint where and how the tissue is susceptible to large-scale damage even
      from single cell mutations.

PMID- 23144965
TI  - Phonological units in spoken word production: insights from Cantonese.
AB  - Evidence from previous psycholinguistic research suggests that phonological units
      such as phonemes have a privileged role during phonological planning in Dutch and
      English (aka the segment-retrieval hypothesis). However, the syllable-retrieval
      hypothesis previously proposed for Mandarin assumes that only the entire syllable
      unit (without the tone) can be prepared in advance in speech planning. Using
      Cantonese Chinese as a test case, the present study was conducted to investigate
      whether the syllable-retrieval hypothesis can be applied to other Chinese spoken
      languages. In four implicit priming (form-preparation) experiments, participants
      were asked to learn various sets of prompt-response di-syllabic word pairs and to
      utter the corresponding response word upon seeing each prompt. The response words
      in a block were either phonologically related (homogeneous) or unrelated
      (heterogeneous). Participants' naming responses were significantly faster in the
      homogeneous than in the heterogeneous conditions when the response words shared
      the same word-initial syllable (without the tone) (Exps.1 and 4) or body (Exps.3
      and 4), but not when they shared merely the same word-initial phoneme (Exp.2).
      Furthermore, the priming effect observed in the syllable-related condition was
      significantly larger than that in the body-related condition (Exp. 4). Although
      the observed syllable priming effects and the null effect of word-initial phoneme
      are consistent with the syllable-retrieval hypothesis, the body-related (sub
      syllabic) priming effects obtained in this Cantonese study are not. These results
      suggest that the syllable-retrieval hypothesis is not generalizable to all
      Chinese spoken languages and that both syllable and sub-syllabic constituents are
      legitimate planning units in Cantonese speech production.

PMID- 23144964
TI  - Endogenous thrombospondin-1 regulates leukocyte recruitment and activation and
      accelerates death from systemic candidiasis.
AB  - Disseminated Candida albicans infection results in high morbidity and mortality
      despite treatment with existing antifungal drugs. Recent studies suggest that
      modulating the host immune response can improve survival, but specific host
      targets for accomplishing this goal remain to be identified. The extracellular
      matrix protein thrombospondin-1 is released at sites of tissue injury and
      modulates several immune functions, but its role in C. albicans pathogenesis has
      not been investigated. Here, we show that mice lacking thrombospondin-1 have an
      advantage in surviving disseminated candidiasis and more efficiently clear the
      initial colonization from kidneys despite exhibiting fewer infiltrating
      leukocytes. By examining local and systemic cytokine responses to C. albicans and
      other standard inflammatory stimuli, we identify a crucial function of phagocytes
      in this enhanced resistance. Subcutaneous air pouch and systemic candidiasis
      models demonstrated that endogenous thrombospondin-1 enhances the early innate
      immune response against C. albicans and promotes activation of inflammatory
      macrophages (inducible nitric oxide synthase+, IL-6(high), TNF-alpha(high), IL
      10(low)), release of the chemokines MIP-2, JE, MIP-1alpha, and RANTES, and CXCR2
      driven polymorphonuclear leukocytes recruitment. However, thrombospondin-1
      inhibited the phagocytic capacity of inflammatory leukocytes in vivo and in
      vitro, resulting in increased fungal burden in the kidney and increased mortality
      in wild type mice. Thus, thrombospondin-1 enhances the pathogenesis of
      disseminated candidiasis by creating an imbalance in the host immune response
      that ultimately leads to reduced phagocytic function, impaired fungal clearance,
      and increased mortality. Conversely, inhibitors of thrombospondin-1 may be useful
      drugs to improve patient recovery from disseminated candidiasis.

PMID- 23144966
TI  - Serum liver fatty acid binding protein levels correlate positively with obesity
      and insulin resistance in Chinese young adults.
AB  - BACKGROUND: Liver fatty acid-binding protein (FABP1) plays an inconclusive role
      in adiposity. We investigated the association of serum FABP1 levels with obesity
      and insulin resistance in Chinese young people under 30 years old. METHODOLOGY
      AND PRINCIPAL FINDINGS: Cross-sectional analysis including 200 obese and 172
      normal-weight subjects matched for age and sex, anthropometric measurements were
      performed and serum FABP1 and biochemical characteristics were measured. Insulin
      resistance was determined by homeostasis model assessment of insulin resistance
      (HOMA-IR) and by the insulin sensitivity index (S(i)) derived from Bergman's
      minimal model. FABP1 levels in obese subjects were significantly higher than
      those in normal-weight subjects (p<0.001) and the significance remained after
      adjustment for age, gender, alanine and aspartate aminotransferases (p<0.001).
      Serum FABP1 levels were significantly correlated with many metabolic-related
      parameters, with BMI and triglycerides as the independent determinants. FABP1
      levels remained an independent risk factor of insulin resistance assessed by
      binary S(i) (OR = 1.868 per SD unit, 95% CI [1.035-3.373], p = 0.038) after
      adjustment for age, sex, BMI, waist circumference, systolic blood pressure, serum
      triacylglycerol, total cholesterol, HDL- and LDL-cholesterol,. FABP1 levels were
      also elevated with an increasing number of components of the metabolic syndrome
      (p for trend <0.001). Multiple regression modeling for the MetS and its
      components demonstrated that hypertriglyceridemia and low HDL-cholesterol were
      significantly correlated to serum FABP1 levels. CONCLUSIONS AND SIGNIFICANCE:
      Serum FABP1 correlates positively with obesity and insulin resistance in Chinese
      young adults. Our data supports the fact that FABP1 might be an important
      mediator participating in fatty acid metabolism and energy balance.

PMID- 23144967
TI  - A molecular phylogeny of Hemiptera inferred from mitochondrial genome sequences.
AB  - Classically, Hemiptera is comprised of two suborders: Homoptera and Heteroptera.
      Homoptera includes Cicadomorpha, Fulgoromorpha and Sternorrhyncha. However,
      according to previous molecular phylogenetic studies based on 18S rDNA,
      Fulgoromorpha has a closer relationship to Heteroptera than to other hemipterans,
      leaving Homoptera as paraphyletic. Therefore, the position of Fulgoromorpha is
      important for studying phylogenetic structure of Hemiptera. We inferred the
      evolutionary affiliations of twenty-five superfamilies of Hemiptera using
      mitochondrial protein-coding genes and rRNAs. We sequenced three mitogenomes,
      from Pyrops candelaria, Lycorma delicatula and Ricania marginalis, representing
      two additional families in Fulgoromorpha. Pyrops and Lycorma are representatives
      of an additional major family Fulgoridae in Fulgoromorpha, whereas Ricania is a
      second representative of the highly derived clade Ricaniidae. The organization
      and size of these mitogenomes are similar to those of the sequenced fulgoroid
      species. Our consensus phylogeny of Hemiptera largely supported the relationships
      (((Fulgoromorpha,Sternorrhyncha),Cicadomorpha),Heteroptera), and thus supported
      the classic phylogeny of Hemiptera. Selection of optimal evolutionary models
      (exclusion and inclusion of two rRNA genes or of third codon positions of protein
      coding genes) demonstrated that rapidly evolving and saturated sites should be
      removed from the analyses.

PMID- 23144968
TI  - In vitro and in vivo activity of an organic tellurium compound on Leishmania
      (Leishmania) chagasi.
AB  - Tellurium compounds have shown several biological properties and recently the
      leishmanicidal effect of one organotellurane was demonstrated. These findings led
      us to test the effect of the organotellurium compound RF07 on Leishmania
      (Leishmania) chagasi, the agent of visceral leishmaniasis in Latin America. In
      vitro assays were performed in L. (L.) chagasi-infected bone marrow derived
      macrophages treated with different concentrations of RF07. In in vivo experiments
      Golden hamsters were infected with L. (L.) chagasi and injected intraperitoneally
      with RF07 whereas control animals received either Glucantime or PBS. The effect
      of RF07 on cathepsin B activity of L. (L.) chagasi amastigotes was assayed
      spectrofluorometrically using fluorogenic substrates. The main findings were: 1)
      RF07 showed significant leishmanicidal activity against intracellular parasites
      at submicromolar concentrations (IC50 of 529.7+/-26.5 nM), and the drug displayed
      10-fold less toxicity to macrophages (CC50 of 5,426+/-272.8 nM); 2) kinetics
      assays showed an increasing leishmanicidal action of RF07 at longer periods of
      treatment; 3) one month after intraperitoneal injection of RF07 L. (L.) chagasi
      infected hamsters showed a reduction of 99.6% of parasite burden when compared to
      controls that received PBS; 4) RF07 inhibited the cathepsin B activity of L. (L.)
      chagasi amastigotes. The present results demonstrated that the tellurium compound
      RF07 is able to destroy L. (L.) chagasi in vitro and in vivo at concentrations
      that are non toxic to the host. We believe these findings support further study
      of the potential of RF07 as a possible alternative for the chemotherapy of
      visceral leishmaniasis.

PMID- 23144970
TI  - Abnormal anatomical connectivity between the amygdala and orbitofrontal cortex in
      conduct disorder.
AB  - OBJECTIVE: Previous research suggested that structural and functional
      abnormalities within the amygdala and orbitofrontal cortex contribute to the
      pathophysiology of Conduct Disorder (CD). Here, we investigated whether the
      integrity of the white-matter pathways connecting these regions is abnormal and
      thus may represent a putative neurobiological marker for CD. METHODS: Diffusion
      Tensor Imaging (DTI) was used to investigate white-matter microstructural
      integrity in male adolescents with childhood-onset CD, compared with healthy
      controls matched in age, sex, intelligence, and socioeconomic status. Two
      approaches were employed to analyze DTI data: voxel-based morphometry of
      fractional anisotropy (FA), an index of white-matter integrity, and virtual
      dissection of white-matter pathways using tractography. RESULTS: Adolescents with
      CD displayed higher FA within the right external capsule relative to controls (T
      = 6.08, P<0.05, Family-Wise Error, whole-brain correction). Tractography analyses
      showed that FA values within the uncinate fascicle (connecting the amygdala and
      orbitofrontal cortex) were abnormally increased in individuals with CD relative
      to controls. This was in contrast with the inferior frontal-occipital fascicle,
      which showed no significant group differences in FA. The finding of increased FA
      in the uncinate fascicle remained significant when factoring out the contribution
      of attention-deficit/hyperactivity disorder symptoms. There were no group
      differences in the number of streamlines in either of these anatomical tracts.
      CONCLUSIONS: These results provide evidence that CD is associated with white
      matter microstructural abnormalities in the anatomical tract that connects the
      amygdala and orbitofrontal cortex, the uncinate fascicle. These results implicate
      abnormal maturation of white-matter pathways which are fundamental in the
      regulation of emotional behavior in CD.

PMID- 23144969
TI  - Differential sialylation of serpin A1 in the early diagnosis of Parkinson's
      disease dementia.
AB  - The prevalence of Parkinson's disease (PD) increases with age. Up to 50% of PD
      show cognitive decline in terms of a mild cognitive impairment already in early
      stages that predict the development of dementia, which can occur in up to 80% of
      PD patients over the long term, called Parkinson's disease dementia (PDD). So
      far, diagnosis of PD/PDD is made according to clinical and neuropsychological
      examinations while laboratory data is only used for exclusion of other diseases.
      The aim of this study was the identification of possible biomarkers in
      cerebrospinal fluid (CSF) of PD, PDD and controls (CON) which predict the
      development of dementia in PD. For this, a proteomic approach optimized for CSF
      was performed using 18 clinically well characterized patients in a first step
      with subsequent validation using 84 patients. Here, we detected differentially
      sialylated isoforms of Serpin A1 as marker for differentiation of PD versus PDD
      in CSF. Performing 2D-immunoblots, all PDD patients could be identified correctly
      (sensitivity 100%). Ten out of 24 PD patients showed Serpin A1 isoforms in a
      similar pattern like PDD, indicating a specificity of 58% for the test-procedure.
      In control samples, no additional isoform was detected. On the basis of these
      results, we conclude that differentially sialylated products of Serpin A1 are an
      interesting biomarker to indicate the development of a dementia during the course
      of PD.

PMID- 23144971
TI  - The influence of shc proteins and aging on whole body energy expenditure and
      substrate utilization in mice.
AB  - While it has been proposed that Shc family of adaptor proteins may influence
      aging by regulating insulin signaling and energy metabolism, the overall impact
      of Shc proteins on whole body energy metabolism has yet to be elucidated. Thus,
      the purpose of this study was to determine the influence of Shc proteins and
      aging on whole body energy metabolism in a mouse model under ambient conditions
      (22 degrees C) and acute cold exposure (12 degrees C for 24 hours). Using
      indirect respiration calorimetry, we investigated the impact of Shc proteins and
      aging on EE and substrate utilization (RQ) in p66 Shc-/- (ShcKO) and wild-type
      (WT) mice. Calorimetry measurements were completed in 3, 15, and 27 mo mice at 22
      degrees C and 12 degrees C. At both temperatures and when analyzed across all age
      groups, ShcKO mice demonstrated lower 24 h total EE values than that of WT mice
      when EE data was expressed as either kJ per mouse, or adjusted by body weight or
      crude organ mass (ORGAN) (P<=0.01 for all). The ShcKO mice also had higher
      (P<0.05) fed state RQ values than WT animals at 22 degrees C, consistent with an
      increase in glucose utilization. However, Shc proteins did not influence age
      related changes in energy expenditure or RQ. Age had a significant impact on EE
      at 22 degrees C, regardless of how EE data was expressed (P<0.05), demonstrating
      a pattern of increase in EE from age 3 to 15 mo, followed by a decrease in EE at
      27 mo. These results indicate a decline in whole body EE with advanced age in
      mice, independent of changes in body weight (BW) or fat free mass (FFM). The
      results of this study indicate that both Shc proteins and aging should be
      considered as factors that influence energy expenditure in mice.

PMID- 23144972
TI  - Valproic acid induces cutaneous wound healing in vivo and enhances keratinocyte
      motility.
AB  - BACKGROUND: Cutaneous wound healing is a complex process involving several
      signaling pathways such as the Wnt and extracellular signal-regulated kinase
      (ERK) signaling pathways. Valproic acid (VPA) is a commonly used antiepileptic
      drug that acts on these signaling pathways; however, the effect of VPA on
      cutaneous wound healing is unknown. METHODS AND FINDINGS: We created full
      thickness wounds on the backs of C3H mice and then applied VPA. After 7 d, we
      observed marked healing and reduced wound size in VPA-treated mice. In the neo
      epidermis of the wounds, beta-catenin and markers for keratinocyte terminal
      differentiation were increased after VPA treatment. In addition, alpha-smooth
      muscle actin (alpha-SMA), collagen I and collagen III in the wounds were
      significantly increased. VPA induced proliferation and suppressed apoptosis of
      cells in the wounds, as determined by Ki67 and terminal deoxynucleotidyl
      transferase dUTP nick end labeling (TUNEL) staining analyses, respectively. In
      vitro, VPA enhanced the motility of HaCaT keratinocytes by activating Wnt/beta
      catenin, ERK and phosphatidylinositol 3-kinase (PI3-kinase)/Akt signaling
      pathways. CONCLUSIONS: VPA enhances cutaneous wound healing in a murine model and
      induces migration of HaCaT keratinocytes.

PMID- 23144973
TI  - Novel SNP Discovery in African Buffalo, Syncerus caffer, using high-throughput
      Sequencing.
AB  - The African buffalo, Syncerus caffer, is one of the most abundant and
      ecologically important species of megafauna in the savannah ecosystem. It is an
      important prey species, as well as a host for a vast array of nematodes,
      pathogens and infectious diseases, such as bovine tuberculosis and corridor
      disease. Large-scale SNP discovery in this species would greatly facilitate
      further research into the area of host genetics and disease susceptibility, as
      well as provide a wealth of sequence information for other conservation and
      genomics studies. We sequenced pools of Cape buffalo DNA from a total of 9
      animals, on an ABI SOLiD4 sequencer. The resulting short reads were mapped to the
      UMD3.1 Bos taurus genome assembly using both BWA and Bowtie software packages. A
      mean depth of 2.7* coverage over the mapped regions was obtained. Btau4 gene
      annotation was added to all SNPs identified within gene regions. Bowtie and BWA
      identified a maximum of 2,222,665 and 276,847 SNPs within the buffalo
      respectively, depending on analysis method. A panel of 173 SNPs was validated by
      fluorescent genotyping in 87 individuals. 27 SNPs failed to amplify, and of the
      remaining 146 SNPs, 43-54% of the Bowtie SNPs and 57-58% of the BWA SNPs were
      confirmed as polymorphic. dN/dS ratios found no evidence of positive selection,
      and although there were genes that appeared to be under negative selection, these
      were more likely to be slowly evolving house-keeping genes.

PMID- 23144974
TI  - Progression of aortic arch calcification over 1 year is an independent predictor
      of mortality in incident peritoneal dialysis patients.
AB  - BACKGROUNDS AND AIMS: The presence and progression of vascular calcification have
      been demonstrated as important risk factors for mortality in dialysis patients.
      However, since the majority of subjects included in most previous studies were
      hemodialysis patients, limited information was available in peritoneal dialysis
      (PD) patients. Therefore, the aim of this study was to investigate the prevalence
      of aortic arch calcification (AoAC) and prognostic value of AoAC progression in
      PD patients. METHODS: We prospectively determined AoAC by chest X-ray at PD start
      and after 12 months, and evaluated the impact of AoAC progression on mortality in
      415 incident PD patients. RESULTS: Of 415 patients, 169 patients (40.7%) had AoAC
      at baseline with a mean of 18.1+/-11.2%. The presence of baseline AoAC was an
      independent predictor of all-cause [Hazard ratio (HR): 2.181, 95% confidence
      interval (CI): 1.336-3.561, P = 0.002] and cardiovascular mortality (HR: 3.582,
      95% CI: 1.577-8.132, P = 0.002). Among 363 patients with follow-up chest X-rays
      at 12 months after PD start, the proportion of patients with AoAC progression was
      significantly higher in patients with baseline AoAC (64.2 vs. 5.3%, P<0.001).
      Moreover, all-cause and cardiovascular death rates were significantly higher in
      the progression groups than in the non-progression group (P<0.001). Multivariate
      Cox analysis revealed that AoAC progression was an independent predictor for all
      cause (HR: 2.625, 95% CI: 1.150-5.991, P = 0.022) and cardiovascular mortality
      (HR: 4.008, 95% CI: 1.079-14.890, P = 0.038) in patients with AoAC at baseline.
      CONCLUSIONS: The presence and progression of AoAC assessed by chest X-ray were
      independently associated with unfavorable outcomes in incident PD patients.
      Regular follow-up by chest X-ray could be a simple and useful method to stratify
      mortality risk in these patients.

PMID- 23144975
TI  - The study of cognitive characteristics in Asperger's disorder by using a modified
      Prisoner's Dilemma game with a variable payoff matrix.
AB  - Individuals with Asperger's Disorder (ASP) have difficulties in social
      reciprocity and in providing appropriate cooperative behavior. The Prisoner's
      Dilemma (PD) is a well-known model in game theory that illustrates the
      paradoxical disposition of interaction between two individuals with opposing
      interests, and may be a useful tool in the diagnosis of ASP in early childhood.
      In this study, we investigated the cognitive characteristics of ASP by using a
      modified PD game. The subjects were 29 individuals with ASP and 28 age- and IQ
      matched controls. In the PD game, each of two players has two cards: card 1
      represents cooperation and card 2 betrayal. The score each player obtains is
      decided according to a 2 x 2 payoff matrix and depends on the combination of
      their selections. The P-score ("P" for punishment) is defined as the score that
      is given when they both select betrayal. Comparing the two groups, the mean P
      score at the end of the game and the mean total score were significantly higher
      in the ASP group, while the rate of selection of cooperative choice in both
      groups did not differ significantly. The classification of the shape of the graph
      according to fluctuation of the P-score revealed that in the ASP group only 2
      cases (6.9%) showed continuous decrease of P-score compared to 8 control cases
      (28.6%) demonstrating similar results. However, the reasons were thought to be
      different: ASP subjects presumably selected card 2 because of a preference for
      the number itself, whereas control subjects preferentially chose this card to
      enhance their chance of winning the competition. It is often difficult to
      diagnose ASP in the young especially when they lack the distinctive clinical
      features of ASD in early childhood. Given the limited number of objective tools
      to evaluate the cognitive characteristics of ASP subjects, the PD game might be a
      useful diagnostic support tool for ASP.

PMID- 23144976
TI  - Protein tyrosine phosphatase receptor type z negatively regulates oligodendrocyte
      differentiation and myelination.
AB  - BACKGROUND: Fyn tyrosine kinase-mediated down-regulation of Rho activity through
      activation of p190RhoGAP is crucial for oligodendrocyte differentiation and
      myelination. Therefore, the loss of function of its counterpart protein tyrosine
      phosphatase (PTP) may enhance myelination during development and remyelination in
      demyelinating diseases. To test this hypothesis, we investigated whether Ptprz, a
      receptor-like PTP (RPTP) expressed abuntantly in oligodendrocyte lineage cells,
      is involved in this process, because we recently revealed that p190RhoGAP is a
      physiological substrate for Ptprz. METHODOLOGY/PRINCIPAL FINDINGS: We found an
      early onset of the expression of myelin basic protein (MBP), a major protein of
      the myelin sheath, and early initiation of myelination in vivo during development
      of the Ptprz-deficient mouse, as compared with the wild-type. In addition,
      oligodendrocytes appeared earlier in primary cultures from Ptprz-deficient mice
      than wild-type mice. Furthermore, adult Ptprz-deficient mice were less
      susceptible to experimental autoimmune encephalomyelitis (EAE) induced by active
      immunization with myelin/oligodendrocyte glycoprotein (MOG) peptide than were
      wild-type mice. After EAE was induced, the tyrosine phosphorylation of p190RhoGAP
      increased significantly, and the EAE-induced loss of MBP was markedly suppressed
      in the white matter of the spinal cord in Ptprz-deficient mice. Here, the number
      of T-cells and macrophages/microglia infiltrating into the spinal cord did not
      differ between the two genotypes after MOG immunization. All these findings
      strongly support the validity of our hypothesis. CONCLUSIONS/SIGNIFICANCE: Ptprz
      plays a negative role in oligodendrocyte differentiation in early central nervous
      system (CNS) development and remyelination in demyelinating CNS diseases, through
      the dephosphorylation of substrates such as p190RhoGAP.

PMID- 23144977
TI  - Five cryptic species in the amazonian catfish Centromochlus existimatus
      identified based on biogeographic predictions and genetic data.
AB  - Accurately quantifying biodiversity is fundamental for both evolutionary theory
      and conservation strategies. DNA-based studies are exposing high cryptic
      diversity irrespective of taxonomic group or environmental setting, and
      increasing the ever-growing estimates of global biodiversity. This has severe
      implications for under-sampled and species-rich tropical regions, such as the
      Amazon Basin. We used biogeographic predictions derived from geomorphological
      history and contemporary hydrochemical and genetic data to examine cryptic
      diversity in the Amazonian driftwood catfish Centromochlus existimatus. Using
      both nuclear and mitochondrial DNA markers, five deeply divergent cryptic
      lineages are reported, for which at least three are sympatric in distribution.
      These lineages appear relatively old, with divergence times dating back to middle
      Miocene. Diversification events appear to be chronologically associated with the
      formation of the modern Amazon River system, and perhaps influenced by
      hydrochemical gradients between tributaries. The cause of apparent morphological
      stasis in the C. existimatus species complex is speculated within the context of
      hydrochemistry and non-visual mating cues and a full taxonomic revision is
      recommended. Our findings suggest that the diversity of Amazonian ichthyofauna is
      vastly underestimated and highlight the relevance of biogeographic predictions to
      guide sampling efforts in ecologically complex and under-studied ecosystems.

PMID- 23144978
TI  - Bio-imaging of colorectal cancer models using near infrared labeled epidermal
      growth factor.
AB  - Novel strategies that target the epidermal growth factor receptor (EGFR) have led
      to the clinical development of monoclonal antibodies, which treat metastatic
      colorectal cancer (mCRC) but only subgroups of patients with increased wild type
      KRAS and EGFR gene copy, respond to these agents. Furthermore, resistance to EGFR
      blockade inevitably occurred, making future therapy difficult. Novel bio-imaging
      (BOI) methods may assist in quantization of EGFR in mCRC tissue thus
      complementing the immunohistochemistry methodology, in guiding the future
      treatment of these patients. The aim of the present study was to explore the
      usefulness of near infrared-labeled EGF (EGF-NIR) for bio-imaging of CRC using in
      vitro and in vivo orthotopic tumor CRC models and ex vivo human CRC tissues. We
      describe the preparation and characterization of EGF-NIR and investigate binding,
      using BOI of a panel of CRC cell culture models resembling heterogeneity of human
      CRC tissues. EGF-NIR was specifically and selectively bound by EGFR expressing
      CRC cells, the intensity of EGF-NIR signal to background ratio (SBR) reflected
      EGFR levels, dose-response and time course imaging experiments provided optimal
      conditions for quantization of EGFR levels by BOI. EGF-NIR imaging of mice with
      HT-29 orthotopic CRC tumor indicated that EGF-NIR is more slowly cleared from the
      tumor and the highest SBR between tumor and normal adjacent tissue was achieved
      two days post-injection. Furthermore, images of dissected tissues demonstrated
      accumulation of EGF-NIR in the tumor and liver. EGF-NIR specifically and strongly
      labeled EGFR positive human CRC tissues while adjacent CRC tissue and EGFR
      negative tissues expressed weak NIR signals. This study emphasizes the use of EGF
      NIR for preclinical studies. Combined with other methods, EGF-NIR could provide
      an additional bio-imaging specific tool in the standardization of measurements of
      EGFR expression in CRC tissues.

PMID- 23144979
TI  - The A736V TMPRSS6 polymorphism influences hepatic iron overload in nonalcoholic
      fatty liver disease.
AB  - BACKGROUND & AIMS: Hepatic iron accumulation due to altered trafficking is
      frequent in patients with nonalcoholic fatty liver disease (NAFLD), and is
      associated with more severe liver damage and hepatocellular carcinoma. The
      p.Ala736Val TMPRSS6 variant influences iron metabolism regulating the
      transcription of the hepatic hormone hepcidin, but its role in the pathogenesis
      of iron overload disorders is controversial. Aim of this study was to evaluate
      the whether the TMPRSS6 p.Ala736Val variant influences hepatic iron accumulation
      in a well-characterized series of Italian patients with histological NAFLD.
      METHODS: 216 patients with histological NAFLD. TMPRSS6 and HFE variants were
      assessed by allele specific PCR, liver histology by the NAFLD activity score and
      Perls' staining for iron. RESULTS: Homozygosity for the p.736Val allele
      previously linked to higher hepcidin did not influence transferrin saturation
      (TS), but was associated with lower hepatic iron stores (p = 0.01), and ferritin
      levels (median 223 IQR 102-449 vs. 308 IQR 141-618 ng/ml; p = 0.01). Homozygosity
      for TMPRSS6 p.736Val was nearly associated with lower ballooning (p = 0.05),
      reflecting hepatocellular damage related to oxidative stress. The influence of
      TMPRSS6 on hepatic iron accumulation was more marked in patients negative for HFE
      genotypes predisposing to iron overload (p.Cys282Tyr + and p.His63Asp +/+; p =
      0.01), and the p.736Val variant was negatively associated with hepatic iron
      accumulation independently of age, gender, HFE genotype, and beta-thalassemia
      trait (OR 0.59, 0.39-0.88). CONCLUSIONS: The p.Ala736Val TMPRSS6 variant
      influences secondary hepatic iron accumulation in patients with NAFLD.

PMID- 23144980
TI  - Re-evaluation of a bacterial antifreeze protein as an adhesin with ice-binding
      activity.
AB  - A novel role for antifreeze proteins (AFPs) may reside in an exceptionally large
      1.5-MDa adhesin isolated from an Antarctic Gram-negative bacterium, Marinomonas
      primoryensis. MpAFP was purified from bacterial lysates by ice adsorption and gel
      electrophoresis. We have previously reported that two highly repetitive
      sequences, region II (RII) and region IV (RIV), divide MpAFP into five distinct
      regions, all of which require mM Ca(2+) levels for correct folding. Also, the
      antifreeze activity is confined to the 322-residue RIV, which forms a Ca(2+)
      bound beta-helix containing thirteen Repeats-In-Toxin (RTX)-like repeats. RII
      accounts for approximately 90% of the mass of MpAFP and is made up of ~120 tandem
      104-residue repeats. Because these repeats are identical in DNA sequence, their
      number was estimated here by pulsed-field gel electrophoresis. Structural
      homology analysis by the Protein Homology/analogY Recognition Engine (Phyre2)
      server indicates that the 104-residue RII repeat adopts an immunoglobulin beta
      sandwich fold that is typical of many secreted adhesion proteins. Additional RTX
      like repeats in RV may serve as a non-cleavable signal sequence for the type I
      secretion pathway. Immunodetection shows both repeated regions are uniformly
      distributed over the cell surface. We suggest that the development of an AFP-like
      domain within this adhesin attached to the bacterial outer surface serves to
      transiently bind the host bacteria to ice. This association would keep the
      bacteria within the upper reaches of the water column where oxygen and nutrients
      are potentially more abundant. This novel envirotactic role would give AFPs a
      third function, after freeze avoidance and freeze tolerance: that of transiently
      binding an organism to ice.

PMID- 23144981
TI  - Distinct effects of guanidine thiocyanate on the structure of superfolder GFP.
AB  - Having a high folding efficiency and a low tendency to aggregate, the superfolder
      GFP (sfGFP) offers a unique opportunity to study the folding of proteins that
      have a beta-barrel topology. Here, we studied the unfolding-refolding of sfGFP
      that was induced by guanidine thiocyanate (GTC), which is a stronger denaturing
      agent than GdnHCl or urea. Structural perturbations of sfGFP were studied by
      spectroscopic methods (absorbance, fluorescence, and circular dichroism), by
      acrylamide quenching of tryptophan and green chromophore fluorescence, and by
      size-exclusion chromatography. Low concentrations of GTC (up to 0.1 M) induce
      subtle changes in the sfGFP structure. The pronounced changes in the visible
      absorption spectrum of sfGFP which are accompanied by a dramatic decrease in
      tryptophan and green chromophore fluorescence was recorded in the range 0-0.7 M
      GNC. These alterations of sfGFP characteristics that erroneously can be mixed up
      with appearance of intermediate state in fact have pure spectroscopic but not
      structural nature. Higher concentrations of GTC (from 0.7 to 1.7 M), induce a
      disruption of the sfGFP structure, that is manifested in simultaneous changes of
      all of the detected parameters. Full recovery of native properties of denaturated
      sfGFP was observed after denaturant removal. The refolding of sfGFP passes
      through the accumulation of the off-pathway intermediate state, in which inner
      alpha-helix and hence green chromophore and Trp57 are still not tuned up to
      (properly integrated into) the already formed beta-barrel scaffold of protein.
      Incorporation of the chromophore in the beta-barrel in the pathway of refolding
      and restoration of its ability to fluoresce occur in a narrow range of GTC
      concentrations from 1.0 to 0.7 M, and a correct insertion of Trp 57 occurs at
      concentrations ranging from 0.7 to 0 M GTC. These two processes determine the
      hysteresis of protein unfolding and refolding.

PMID- 23144982
TI  - Human herpesvirus-6A/B binds to spermatozoa acrosome and is the most prevalent
      herpesvirus in semen from sperm donors.
AB  - An analysis of all known human herpesviruses has not previously been reported on
      sperm from normal donors. Using an array-based detection method, we determined
      the cross-sectional frequency of human herpesviruses in semen from 198 Danish
      sperm donors. Fifty-five of the donors had at least one ejaculate that was
      positive for one or more human herpesvirus. Of these 27.3% (n = 15) had a double
      herpesvirus infection. If corrected for the presence of multiple ejaculates from
      some donors, the adjusted frequency of herpesviruses in semen was 27.2% with HSV
      1 in 0.4%; HSV-2 in 0.1%; EBV in 6.3%; HCMV in 2.7%; HHV-6A/B in 13.5%; HHV-7 in
      4.2%, whereas none of the samples had detectable VZV or HHV-8. Subsequently, we
      examined longitudinally data on ejaculates from 11 herpesvirus-positive donors.
      Serial analyses revealed that a donor who tested positive for herpesvirus at one
      time point did not necessarily remain positive over time. For the most frequently
      found herpesvirus, HHV-6A/B, we examined its association with sperm. For HHV-6A/B
      PCR-positive semen samples, HHV-6A/B could be detected on the sperm by flow
      cytometry. Conversely, PCR-negative semen samples were negative by flow
      cytometry. HHV-6B was shown to associate with sperm within minutes in a
      concentration dependent manner. Confocal microscopy demonstrated that HHV-6B
      associated with the sperm head, but only to sperm with an intact acrosome. Taken
      together, our data suggest that HHV-6A/B could be transported to the uterus via
      binding to the sperm acrosome. Moreover, we find a 10 times higher frequency of
      HHV-7 in semen from healthy individuals than previously detected. Further
      research is required to determine the potential risk of using herpesvirus
      positive donor semen. Longitudinally analyses of ejaculate series indicate that
      implementation of quarantine for a donor shown to shed a herpesvirus is not a
      tenable solution.

PMID- 23144983
TI  - Endosperm tolerance of paternal aneuploidy allows radiation hybrid mapping of the
      wheat D-genome and a measure of gamma ray-induced chromosome breaks.
AB  - Physical mapping and genome sequencing are underway for the ~17 Gb wheat genome.
      Physical mapping methods independent of meiotic recombination, such as radiation
      hybrid (RH) mapping, will aid precise anchoring of BAC contigs in the large
      regions of suppressed recombination in Triticeae genomes. Reports of endosperm
      development following pollination with irradiated pollen at dosages that cause
      embryo abortion prompted us to investigate endosperm as a potential source of RH
      mapping germplasm. Here, we report a novel approach to construct RH based
      physical maps of all seven D-genome chromosomes of the hexaploid wheat 'Chinese
      Spring', simultaneously. An 81-member subset of endosperm samples derived from 20
      Gy irradiated pollen was genotyped for deletions, and 737 markers were mapped on
      seven D-genome chromosomes. Analysis of well-defined regions of six chromosomes
      suggested a map resolution of ~830 kb could be achieved; this estimate was
      validated with assays of markers from a sequenced contig. We estimate that the
      panel contains ~6,000 deletion bins for D-genome chromosomes and will require
      ~18,000 markers for high resolution mapping. Map-based deletion estimates
      revealed a majority of 1-20 Mb interstitial deletions suggesting mutagenic repair
      of double-strand breaks in pollen provides a useful resource for RH mapping and
      map based cloning studies.

PMID- 23144984
TI  - Apricot melanoidins prevent oxidative endothelial cell death by counteracting
      mitochondrial oxidation and membrane depolarization.
AB  - The cardiovascular benefits associated with diets rich in fruit and vegetables
      are thought to be due to phytochemicals contained in fresh plant material.
      However, whether processed plant foods provide the same benefits as unprocessed
      ones is an open question. Melanoidins from heat-processed apricots were isolated
      and their presence confirmed by colorimetric analysis and browning index.
      Oxidative injury of endothelial cells (ECs) is the key step for the onset and
      progression of cardiovascular diseases (CVD), therefore the potential protective
      effect of apricot melanoidins on hydrogen peroxide-induced oxidative
      mitochondrial damage and cell death was explored in human ECs. The redox state of
      cytoplasmic and mitochondrial compartments was detected by using the redox
      sensitive, fluorescent protein (roGFP), while the mitochondrial membrane
      potential (MMP) was assessed with the fluorescent dye, JC-1. ECs exposure to
      hydrogen peroxide, dose-dependently induced mitochondrial and cytoplasmic
      oxidation. Additionally detected hydrogen peroxide-induced phenomena were MMP
      dissipation and ECs death. Pretreatment of ECs with apricot melanoidins,
      significantly counteracted and ultimately abolished hydrogen peroxide-induced
      intracellular oxidation, mitochondrial depolarization and cell death. In this
      regard, our current results clearly indicate that melanoidins derived from heat
      processed apricots, protect human ECs against oxidative stress.

PMID- 23144985
TI  - Mortality associated with diabetes and cardiovascular disease in older women.
AB  - BACKGROUND: Current guidelines for the prevention of cardiovascular disease (CVD)
      recommend diabetes as a CVD risk equivalent. However, reports that have examined
      the risk of diabetes in comparison to pre-existing CVD are lacking among older
      women. We aimed to assess whether diabetes was associated with a similar risk of
      total and cause-specific mortality as a history of CVD in older women.
      METHODOLOGY/PRINCIPAL FINDINGS: We studied 9218 women aged 68 years or older
      enrolled in a prospective cohort study (Study of Osteoporotic Fracture) during a
      mean follow-up period of 11.7 years and compared all-cause, cardiovascular and
      coronary heart disease mortality among 4 groups: non-diabetic women with and
      without existing CVD, diabetic women with and without existing CVD. Mean (SD) age
      of the participants was 75.2 (5.3) years, 3.5% reported diabetes and 6.8%
      reported existing CVD. During follow-up, 5117 women died with 36% from CVD. The
      multivariate adjusted risk of cardiovascular mortality was increased among both
      non-diabetic women with CVD (hazard ratio (HR) 2.32, 95% CI: 1.97-2.74, P<0.001)
      and diabetic women without CVD (HR 2.06, CI: 1.62-2.64, P<0.001) compared to non
      diabetic women without existing CVD. All-cause, cardiovascular and coronary
      mortality of non-diabetic women with CVD were not significantly different from
      diabetic women without CVD. CONCLUSIONS/SIGNIFICANCE: Older diabetic women
      without CVD have a similar risk of cardiovascular mortality compared to non
      diabetic women with pre-existing CVD. The equivalence of diabetes and CVD seems
      to extend to older women, supporting current guidelines for cardiovascular
      prevention.

PMID- 23144986
TI  - What is the optimal threshold at which to recommend breast biopsy?
AB  - BACKGROUND: A 2% threshold, traditionally used as a level above which breast
      biopsy recommended, has been generalized to all patients from several specific
      situations analyzed in the literature. We use a sequential decision analytic
      model considering clinical and mammography features to determine the optimal
      general threshold for image guided breast biopsy and the sensitivity of this
      threshold to variation of these features. METHODOLOGY/PRINCIPAL FINDINGS: We
      built a decision analytical model called a Markov Decision Process (MDP) model,
      which determines the optimal threshold of breast cancer risk to perform breast
      biopsy in order to maximize a patient's total quality-adjusted life years
      (QALYs). The optimal biopsy threshold is determined based on a patient's
      probability of breast cancer estimated by a logistic regression model (LRM) which
      uses demographic risk factors (age, family history, and hormone use) and
      mammographic findings (described using the established lexicon-BI-RADS). We
      estimate the MDP model's parameters using SEER data (prevalence of invasive vs.
      in situ disease, stage at diagnosis, and survival), US life tables (all cause
      mortality), and the medical literature (biopsy disutility and treatment efficacy)
      to determine the optimal "base case" risk threshold for breast biopsy and perform
      sensitivity analysis. The base case MDP model reveals that 2% is the optimal
      threshold for breast biopsy for patients between 42 and 75 however the thresholds
      below age 42 is lower (1%) and above age 75 is higher (range of 3-5%). Our
      sensitivity analysis reveals that the optimal biopsy threshold varies most
      notably with changes in age and disutility of biopsy. CONCLUSIONS/SIGNIFICANCE:
      Our MDP model validates the 2% threshold currently used for biopsy but shows this
      optimal threshold varies substantially with patient age and biopsy disutility.

PMID- 23144987
TI  - Stelis zootrophionoides (Orchidaceae: Pleurothallidinae), a new species from
      Mexico.
AB  - BACKGROUND: Stelis (Orchidaceae) encompasses approximately 1100 species of
      epiphytic orchids distributed throughout the Neotropics, with the highest
      diversity in Andean South America. Sixty-two species were recorded previously in
      Mexico. METHODS: We formally describe here Stelis zootrophionoides as a new
      species from Chiapas, Mexico. To determine its systematic position, we conducted
      a morphological comparison with other members of Pleurothallidinae and a
      phylogenetic analysis of nucleotide sequences from the plastid matK/trnK and
      trnL/trnF regions, as well as the nuclear ribosomal ITS region for 52 species of
      Pleurothallidinae. Sequences of 49 species were downloaded from GenBank and those
      of three species, including the new taxon, were newly generated for this work.
      The new species is described and illustrated; notes on its ecological preferences
      and a comparison with closely related species are presented. CONCLUSIONS: The new
      species, known only from one location and apparently restricted to the cloud
      forest in the central highlands of Chiapas, Mexico, is considered a rare species.
      This small epiphyte is unique among the Mexican species of Stelis by the
      combination of dark purple flowers with the distal third of the dorsal sepal
      adhered to the apices of the lateral sepals, which are partially united into a
      bifid synsepal, leaving two lateral window-like openings, and sagittate labellum.
      Stelis jalapensis, known from southern Mexico and Guatemala, also has the apices
      of the sepals adhered to each other, but it is distinguished by its larger
      flowers with lanceolate, acute dorsal sepal, completely fused lateral sepals
      (i.e. the synsepal is not bifid), and oblong-elliptic labellum. The phylogenetic
      analysis shows that S. zootrophionoides is closely related to other Mexican
      Stelis and corroborates previous suggestions that fused sepal apices have arisen
      independently in different lineages of Pleurothallidinae.

PMID- 23144988
TI  - 3D differentiation of neural stem cells in macroporous photopolymerizable
      hydrogel scaffolds.
AB  - Neural stem/progenitor cells (NSPCs) are the stem cell of the adult central
      nervous system (CNS). These cells are able to differentiate into the major cell
      types found in the CNS (neurons, oligodendrocytes, astrocytes), thus NSPCs are
      the mechanism by which the adult CNS could potentially regenerate after injury or
      disorder. Microenviromental factors are critical for guiding NSPC differentiation
      and are thus important for neural tissue engineering. In this study, D-mannitol
      crystals were mixed with photocrosslinkable methacrylamide chitosan (MAC) as a
      porogen to enhance pore size during hydrogel formation. D-mannitol was admixed to
      MAC at 5, 10 and 20 wt% D-mannitol per total initial hydrogel weight. D-mannitol
      crystals were observed to dissolve and leave the scaffold within 1 hr.
      Quantification of resulting average pore sizes showed that D-mannitol addition
      resulted in larger average pore size (5 wt%, 4060+/-160 um(2), 10 wt%, 6330+/
      1160 um(2), 20 wt%, 7600+/-1550 um(2)) compared with controls (0 wt%, 3150+/-220
      um(2)). Oxygen diffusion studies demonstrated that larger average pore area
      resulted in enhanced oxygen diffusion through scaffolds. Finally, the
      differentiation responses of NSPCs to phenotypic differentiation conditions were
      studied for neurons, astrocytes and oligodendrocytes in hydrogels of varied
      porosity over 14 d. Quantification of total cell numbers at day 7 and 14, showed
      that cell numbers decreased with increased porosity and over the length of the
      culture. At day 14 immunohistochemistry quantification for primary cell types
      demonstrated significant differentiation to the desired cells types, and that
      total percentages of each cell type was greatest when scaffolds were more porous.
      These results suggest that larger pore sizes in MAC hydrogels effectively promote
      NSPC 3D differentiation.

PMID- 23144989
TI  - Previous exercise training has a beneficial effect on renal and cardiovascular
      function in a model of diabetes.
AB  - Exercise training (ET) is an important intervention for chronic diseases such as
      diabetes mellitus (DM). However, it is not known whether previous exercise
      training intervention alters the physiological and medical complications of these
      diseases. We investigated the effects of previous ET on the progression of renal
      disease and cardiovascular autonomic control in rats with streptozotocin (STZ)
      induced DM. Male Wistar rats were divided into five groups. All groups were
      followed for 15 weeks. Trained control and trained diabetic rats underwent 10
      weeks of exercise training, whereas previously trained diabetic rats underwent 14
      weeks of exercise training. Renal function, proteinuria, renal sympathetic nerve
      activity (RSNA) and the echocardiographic parameters autonomic modulation and
      baroreflex sensitivity (BRS) were evaluated. In the previously trained group, the
      urinary albumin/creatinine ratio was reduced compared with the sedentary diabetic
      and trained diabetic groups (p<0.05). Additionally, RSNA was normalized in the
      trained diabetic and previously trained diabetic animals (p<0.05). The ejection
      fraction was increased in the previously trained diabetic animals compared with
      the diabetic and trained diabetic groups (p<0.05), and the myocardial performance
      index was improved in the previously trained diabetic group compared with the
      diabetic and trained diabetic groups (p<0.05). In addition, the previously
      trained rats had improved heart rate variability and BRS in the tachycardic
      response and bradycardic response in relation to the diabetic group (p<0.05).
      This study demonstrates that previous ET improves the functional damage that
      affects DM. Additionally, our findings suggest that the development of renal and
      cardiac dysfunction can be minimized by 4 weeks of ET before the induction of DM
      by STZ.

PMID- 23144990
TI  - Molecular and kinetic properties of two acetylcholinesterases from the western
      honey bee, Apis mellifera.
AB  - We investigated the molecular and kinetic properties of two acetylcholinesterases
      (AmAChE1 and AmAChE2) from the Western honey bee, Apis mellifera. Western blot
      analysis revealed that AmAChE2 has most of catalytic activity rather than
      AmAChE1, further suggesting that AmAChE2 is responsible for synaptic transmission
      in A. mellifera, in contrast to most other insects. AmAChE2 was predominately
      expressed in the ganglia and head containing the central nervous system (CNS),
      while AmAChE1 was abundantly observed not only in the CNS but also in the
      peripheral nervous system/non-neuronal tissues. Both AmAChEs exist as homodimers;
      the monomers are covalently connected via a disulfide bond under native
      conditions. However, AmAChE2 was associated with the cell membrane via the
      glycophosphatidylinositol anchor, while AmAChE1 was present as a soluble form.
      The two AmAChEs were functionally expressed with a baculovirus system. Kinetic
      analysis revealed that AmAChE2 has approximately 2,500-fold greater catalytic
      efficiency toward acetylthiocholine and butyrylthiocholine than AmAChE1,
      supporting the synaptic function of AmAChE2. In addition, AmAChE2 likely serves
      as the main target of the organophosphate (OP) and carbamate (CB) insecticides as
      judged by the lower IC(50) values against AmAChE2 than against AmAChE1. When OP
      and CB insecticides were pre-incubated with a mixture of AmAChE1 and AmAChE2, a
      significant reduction in the inhibition of AmAChE2 was observed, suggesting a
      protective role of AmAChE1 against xenobiotics. Taken together, based on their
      tissue distribution pattern, molecular and kinetic properties, AmAChE2 plays a
      major role in synaptic transmission, while AmAChE1 has non-neuronal functions,
      including chemical defense.

PMID- 23144992
TI  - Preparing offspring for a dangerous world: potential costs of being wrong.
AB  - Adaptive maternal responses to stressful environments before young are born can
      follow two non-exclusive pathways: either the mother reduces current investment
      in favor of future investment, or influences offspring growth and development in
      order to fit offspring phenotype to the stressful environment. Inducing such
      developmental cues, however, may be risky if the environment changes meanwhile,
      resulting in maladapted offspring. Here we test the effects of a predator-induced
      maternal effect in a predator-free postnatal environment. We manipulated
      perceived predation-risk for breeding female great tits by exposing them to
      stuffed models of either a predatory bird or a non-predatory control. Offspring
      were raised either in an environment matching the maternal one by exchanging
      whole broods within a maternal treatment group, or in a mismatching environment
      by exchanging broods among the maternal treatments. Offspring growth depended on
      the matching of the two environments. While for offspring originating from
      control treated mothers environmental mismatch did not significantly change
      growth, offspring of mothers under increased perceived predation risk grew faster
      and larger in matching conditions. Offspring of predator treated mothers fledged
      about one day later when growing under mismatching conditions. This suggests
      costs paid by the offspring if mothers predict environmental conditions wrongly.

PMID- 23144993
TI  - Identification and characterization of a new autoimmune protein in membranous
      nephropathy by immunoscreening of a renal cDNA library.
AB  - Membranous Nephropathy (MN) represents a large amount of Nephrotic Syndromes in
      the adult population and its definitive diagnosis is currently carried out
      through biopsy. An autoimmune condition has been demonstrated in idiopathic MN
      (iMN) in which some kidney structures are targeted by patient autoantibodies.
      Some candidate antigens have been described and other likely involved target
      proteins responsible for the disease are not known yet. In this work our aim is
      to identify these proteins by screening a lambda-phage library with patients'
      sera. We enrolled four groups of patients: two MN groups of 12 full iMN patients;
      one control group of 15 patients suffering from other renal diseases; one control
      group of 15 healthy individuals. A commercial cDNA phagemide library was screened
      using the above described sera, in order to detect positive signals due to
      antigen-antibody bond. We detected one phagemide clone expressing a protein which
      was shown to be targeted by the antibodies of the iMN sera only. Control sera
      were negative. The sequence analysis of cDNA matched the Synaptonemal Complex
      protein 65 (SC65) coding sequence. Further proteomic analyses were carried out to
      validate our results. We provide evidence of an involvement of SC65 protein as an
      autoimmune target in iMN. Considering the invasiveness and the resulting risk
      coming from renal biopsy, our ongoing aim is to set a procedure able to diagnose
      affected patients through a little- or non-invasive method such as blood sampling
      rather than biopsy.

PMID- 23144991
TI  - Long-term survival in HIV positive patients with up to 15 Years of antiretroviral
      therapy.
AB  - BACKGROUND: Life expectancy has increased for newly diagnosed HIV patients since
      the inception of combination antiretroviral treatment (cART), but there remains a
      need to better understand the characteristics of long-term survival in HIV
      positive patients. We examined long-term survival in HIV-positive patients
      receiving cART in the Australian HIV Observational Database (AHOD), to describe
      changes in mortality compared to the general population and to develop longer
      term survival models. METHODS: Data were examined from 2,675 HIV-positive
      participants in AHOD who started cART. Standardised mortality ratios (SMR) were
      calculated by age, sex and calendar year across prognostic characteristics using
      Australian Bureau of Statistics national data as reference. SMRs were examined by
      years of duration of cART by CD4 and similarly by viral load. Survival was
      analysed using Cox-proportional hazards and parametric survival models. RESULTS:
      The overall SMR for all-cause mortality was 3.5 (95% CI: 3.0-4.0). SMRs by CD4
      count were 8.6 (95% CI: 7.2-10.2) for CD4<350 cells/ul; 2.1 (95% CI: 1.5-2.9) for
      CD4 = 350-499 cells/ul; and 1.5 (95% CI: 1.1-2.0) for CD4>=500 cells/ul. SMRs for
      patients with CD4 counts <350 cells/uL were much higher than for patients with
      higher CD4 counts across all durations of cART. SMRs for patients with viral
      loads greater than 400 copies/ml were much higher across all durations of cART.
      Multivariate models demonstrated improved survival associated with increased
      recent CD4, reduced recent viral load, younger patients, absence of HBVsAg
      positive ever, year of HIV diagnosis and incidence of ADI. Parametric models
      showed a fairly constant mortality risk by year of cART up to 15 years of
      treatment. CONCLUSION: Observed mortality remained fairly constant by duration of
      cART and was modelled accurately by accepted prognostic factors. These rates did
      not vary much by duration of treatment. Changes in mortality with age were
      similar to those in the Australian general population.

PMID- 23144994
TI  - Altered topological organization of white matter structural networks in patients
      with neuromyelitis optica.
AB  - OBJECTIVE: To investigate the topological alterations of the whole-brain white
      matter (WM) structural networks in patients with neuromyelitis optica (NMO).
      METHODS: The present study involved 26 NMO patients and 26 age- and sex-matched
      healthy controls. WM structural connectivity in each participant was imaged with
      diffusion-weighted MRI and represented in terms of a connectivity matrix using
      deterministic tractography method. Graph theory-based analyses were then
      performed for the characterization of brain network properties. A multiple linear
      regression analysis was performed on each network metric between the NMO and
      control groups. RESULTS: The NMO patients exhibited abnormal small-world network
      properties, as indicated by increased normalized characteristic path length,
      increased normalized clustering and increased small-worldness. Furthermore,
      largely similar hub distributions of the WM structural networks were observed
      between NMO patients and healthy controls. However, regional efficiency in
      several brain areas of NMO patients was significantly reduced, which were mainly
      distributed in the default-mode, sensorimotor and visual systems. Furthermore, we
      have observed increased regional efficiency in a few brain regions such as the
      orbital parts of the superior and middle frontal and fusiform gyri. CONCLUSION:
      Although the NMO patients in this study had no discernible white matter T2
      lesions in the brain, we hypothesize that the disrupted topological organization
      of WM networks provides additional evidence for subtle, widespread cerebral WM
      pathology in NMO.

PMID- 23144995
TI  - Quantifying agreement between anatomical and functional interhemispheric
      correspondences in the resting brain.
AB  - The human brain is composed of two broadly symmetric cerebral hemispheres, with
      an abundance of reciprocal anatomical connections between homotopic locations.
      However, to date, studies of hemispheric symmetries have not identified
      correspondency precisely due to variable cortical folding patterns. Here we
      present a method to establish accurate correspondency using position on the
      unfolded cortical surface relative to gyral and sulcal landmarks. The landmark
      method is shown to outperform the method of reversing standard volume
      coordinates, and it is used to quantify the functional symmetry in resting fMRI
      data throughout the cortex. Resting brain activity was found to be maximally
      correlated with locations less than 1 cm away on the cortical surface from the
      corresponding anatomical location in nearly half of the cortex. While select
      locations exhibited asymmetric patterns, precise symmetric relationships were
      found to be the norm, with fine-grained symmetric functional maps demonstrated in
      motor, occipital, and inferior frontal cortex.

PMID- 23144996
TI  - Generation and characterization of a defective HIV-1 Virus as an immunogen for a
      therapeutic vaccine.
AB  - BACKGROUND: The generation of new immunogens able to elicit strong specific
      immune responses remains a major challenge in the attempts to obtain a
      prophylactic or therapeutic vaccine against HIV/AIDS. We designed and constructed
      a defective recombinant virus based on the HIV-1 genome generating infective but
      non-replicative virions able to elicit broad and strong cellular immune responses
      in HIV-1 seropositive individuals. RESULTS: Viral particles were generated
      through transient transfection in producer cells (293-T) of a full length HIV-1
      DNA carrying a deletion of 892 base pairs (bp) in the pol gene encompassing the
      sequence that codes for the reverse transcriptase (NL4-3/DeltaRT clone). The
      viral particles generated were able to enter target cells, but due to the absence
      of reverse transcriptase no replication was detected. The immunogenic capacity of
      these particles was assessed by ELISPOT to determine gamma-interferon production
      in a cohort of 69 chronic asymptomatic HIV-1 seropositive individuals.
      Surprisingly, defective particles produced from NL4-3/DeltaRT triggered stronger
      cellular responses than wild-type HIV-1 viruses inactivated with Aldrithiol-2 (AT
      2) and in a larger proportion of individuals (55% versus 23% seropositive
      individuals tested). Electron microscopy showed that NL4-3/DeltaRT virions
      display immature morphology. Interestingly, wild-type viruses treated with
      Amprenavir (APV) to induce defective core maturation also induced stronger
      responses than the same viral particles generated in the absence of protease
      inhibitors. CONCLUSIONS: We propose that immature HIV-1 virions generated from
      NL4-3/DeltaRT viral clones may represent new prototypes of immunogens with a
      safer profile and stronger capacity to induce cellular immune responses than wild
      type inactivated viral particles.

PMID- 23144997
TI  - An Endogenous Electron Spin Resonance (ESR) signal discriminates nevi from
      melanomas in human specimens: a step forward in its diagnostic application.
AB  - Given the specific melanin-associated paramagnetic features, the Electron Spin
      Resonance (ESR, called also Electron Paramagnetic Resonance, EPR) analysis has
      been proposed as a potential tool for non-invasive melanoma diagnosis. However,
      studies comparing human melanoma tissues to the most appropriate physiological
      counterpart (nevi) have not been performed, and ESR direct correlation with
      melanoma clinical features has never been investigated. ESR spectrum was obtained
      from melanoma and non-melanoma cell-cultures as well as mouse melanoma and non
      melanoma tissues and an endogenous ESR signal (g = 2.005) was found in human
      melanoma cells and in primary melanoma tissues explanted from mice, while it was
      always absent in non-melanoma samples. These characteristics of the measured ESR
      signal strongly suggested its connection with melanin. Quantitative analyses were
      then performed on paraffin-embedded human melanoma and nevus sections, and
      validated on an independent larger validation set, for a total of 112 sections
      (52 melanomas, 60 nevi). The ESR signal was significantly higher in melanomas (p
      = 0.0002) and was significantly different between "Low Breslow's and "High
      Breslow's" depth melanomas (p<0.0001). A direct correlation between ESR signal
      and Breslow's depth, expressed in millimetres, was found (R = 0.57; p<0.0001).
      The eu/pheomelanin ratio was found to be significantly different in melanomas
      "Low Breslow's" vs melanomas "High Breslow's" depth and in nevi vs melanomas
      "High Breslow's depth". Finally, ROC analysis using ESR data discriminated
      melanomas sections from nevi sections with up to 90% accuracy and p<0.0002. In
      the present study we report for the first time that ESR signal in human paraffin
      embedded nevi is significantly lower than signal in human melanomas suggesting
      that spectrum variations may be related to qualitative melanin differences
      specifically occurring in melanoma cells. We therefore conclude that this ESR
      signal may represent a reliable marker for melanoma diagnosis in human
      histological sections.

PMID- 23144998
TI  - Type 2 diabetes associated changes in the plasma non-esterified fatty acids,
      oxylipins and endocannabinoids.
AB  - Type 2 diabetes has profound effects on metabolism that can be detected in
      plasma. While increases in circulating non-esterified fatty acids (NEFA) are well
      described in diabetes, effects on signaling lipids have received little
      attention. Oxylipins and endocannabinoids are classes of bioactive fatty acid
      metabolites with many structural members that influence insulin signaling,
      adipose function and inflammation through autocrine, paracrine and endocrine
      mechanisms. To link diabetes-associated changes in plasma NEFA and signaling
      lipids, we quantitatively targeted >150 plasma lipidome components in age- and
      body mass index-matched, overweight to obese, non-diabetic (n = 12) and type 2
      diabetic (n = 43) African-American women. Diabetes related NEFA patterns
      indicated ~60% increase in steroyl-CoA desaturase activity and ~40% decrease in
      very long chain polyunsaturated fatty acid chain shortening, patterns previously
      associated with the development of nonalcoholic fatty liver disease. Further,
      epoxides and ketones of eighteen carbon polyunsaturated fatty acids were elevated
      >80% in diabetes and strongly correlated with changes in NEFA, consistent with
      their liberation during adipose lipolysis. Endocannabinoid behavior differed by
      class with diabetes increasing an array of N-acylethanolamides which were
      positively correlated with pro-inflammatory 5-lipooxygenase-derived metabolites,
      while monoacylglycerols were negatively correlated with body mass. These results
      clearly show that diabetes not only results in an increase in plasma NEFA, but
      shifts the plasma lipidomic profiles in ways that reflect the biochemical and
      physiological changes of this pathological state which are independent of obesity
      associated changes.

PMID- 23145000
TI  - Cleft, crevice, or the inner thigh: 'another place' for the establishment of the
      invasive barnacle Austrominius modestus (Darwin, 1854).
AB  - The proliferation of anthropogenic infrastructure in the marine environment has
      aided the establishment and spread of invasive species. These structures can
      create novel habitats in areas normally characterised as void of suitable
      settlement sites. The habitat requirements of the invasive acorn barnacle
      Austrominius modestus (Darwin, 1854) were assessed using a novel sampling site at
      Crosby Beach, Liverpool. Austrominius modestus has spread rapidly around the UK
      since its initial introduction, becoming locally dominant in many estuarine areas
      including the Antony Gormley art installation, 'Another Place', at Crosby Beach.
      The installation consists of 100 replicate solid cast-iron life-size human
      figures, located at a range of heights on the shore. We recorded the distribution
      and abundance of A. modestus present on all of the statues at various positions
      during the summer of 2006. The positions varied in location, exposure, direction,
      and rugosity. Although parameters such as rugosity and exposure did influence
      patterns of recruitment, they were less important than interactions between shore
      height and direction, and specific location on the beach. The addition of a
      suitable substrate to a sheltered and estuarine region of Liverpool Bay has
      facilitated the establishment of A. modestus. Understanding the habitat
      requirements of invasive species is important if we are to make predictions about
      their spread and the likelihood of invasion success. Austrominius modestus has
      already become locally dominant in some regions of the UK and, with projections
      of favourable warming conditions and the global expansion of artificial
      structures, the continued spread of this species can be expected. The
      implications of this on the balance between native and invasive species dominance
      should be considered.

PMID- 23144999
TI  - Lack of developmental redundancy between Unc45 proteins in zebrafish muscle
      development.
AB  - Since the majority of protein-coding genes in vertebrates have intra-genomic
      homologues, it has been difficult to eliminate the potential of functional
      redundancy from analyses of mutant phenotypes, whether produced by genetic lesion
      or transient knockdown. Further complicating these analyses, not all gene
      products have activities that can be assayed in vitro, where the efficiency of
      the various family members can be compared against constant substrates. Two
      vertebrate UNC-45 homologues, unc45a and unc45b, affect distinct stages of muscle
      differentiation when knocked down in cell culture and are functionally redundant
      in vitro. UNC-45 proteins are members of the UCS (UNC-45/CRO1/She4p) protein
      family that has been shown to regulate myosin-dependent functions from fungi to
      vertebrates through direct interaction with the myosin motor domain. To test
      whether the same functional relationship exists between these unc45 paralogs in
      vivo, we examined the developmental phenotypes of doubly homozygous unc45b(-/-);
      unc45a(-/-) mutant zebrafish embryos. We focused specifically on the combined
      effects on morphology and gene expression resulting from the zygotic lack of both
      paralogs. We found that unc45b(-/-) and unc45b(-/-); unc45a(-/-) embryos were
      phenotypically indistinguishable with both mutants displaying identical cardiac,
      skeletal muscle, and jaw defects. We also found no evidence to support a role for
      zygotic Unc45a function in myoblast differentiation. In contrast to previous in
      vitro work, this rules out a model of functional redundancy between Unc45a and
      Unc45b in vivo. Instead, our phylogenetic and phenotypic analyses provide
      evidence for the role of functional divergence in the evolution of the UCS
      protein family.

PMID- 23145001
TI  - SRC kinase regulation in progressively invasive cancer.
AB  - Metastatic progression is a multistep process that involves tumor growth and
      survival, motility and invasion, and subsequent proliferation in an inappropriate
      environment. The Src protein tyrosine kinase has been implicated in many of the
      biochemical pathways that drive these behaviors. Although Src itself is only
      rarely mutated in human tumors, its aberrant activity has been noted in various
      cancers and suggested to serve as a barometer of metastatic potential. With these
      features in mind, we examined Src kinase regulation at the structural, enzymatic,
      and expression levels as a function of progressively invasive prostate cancer
      cell lines. Surprisingly, both total Src content and kinase activity decrease
      with increasing cell line aggressiveness, an observation that appears to be
      inconsistent with the well-documented role of Src in the signaling pathways that
      drive growth and invasion. However, we do observe a direct correlation between
      Src kinase specific activity (total Src kinase activity/total Src content) and
      metastatic aggressiveness, possibly suggesting that in highly aggressive cell
      lines, key signaling enzymes are globally recruited to drive the cancerous
      phenotype. In addition, although the expected enhanced phosphorylation of Src at
      Tyr-416 (activation site) is present in the most aggressive prostate cancer cell
      lines, unexpectedly high phosphorylation levels at the Tyr-527 inhibitory site
      are observed as well. The latter, rather than representative of inhibited enzyme,
      is more indicative of primed Src responsive to local phosphorylated binding
      partners.

PMID- 23145003
TI  - Alterations in DRBD3 ribonucleoprotein complexes in response to stress in
      Trypanosoma brucei.
AB  - Regulation of RNA polymerase II transcription initiation is apparently absent in
      trypanosomes. Instead, these eukaryotes control gene expression mainly at the
      post-transcriptional level. Regulation is exerted through the action of numerous
      RNA-binding proteins that modulate mRNA processing, turnover, translation and
      localization. In this work we show that the RNA-binding protein DRBD3 resides in
      the cytoplasm, but localizes to the nucleus upon oxidative challenge and to
      stress granules under starvation conditions. DRBD3 associates with other proteins
      to form a complex, the composition of which is altered by cellular stress.
      Interestingly, target mRNAs remain bound to DRBD3 under stress conditions. Our
      results suggest that DRBD3 transports regulated mRNAs within the cell in the form
      of ribonucleoprotein complexes that are remodeled in response to environmental
      cues.

PMID- 23145002
TI  - Apoptosis-related gene expression profiles of mouse ESCs and maGSCs: role of Fgf4
      and Mnda in pluripotent cell responses to genotoxicity.
AB  - Stem cells in the developing embryo proliferate and differentiate while
      maintaining genomic integrity, failure of which may lead to accumulation of
      mutations and subsequent damage to the embryo. Embryonic stem cells (ESCs), the
      in vitro counterpart of embryo stem cells are highly sensitive to genotoxic
      stress. Defective ESCs undergo either efficient DNA damage repair or apoptosis,
      thus maintaining genomic integrity. However, the genotoxicity- and apoptosis
      related processes in germ-line derived pluripotent cells, multipotent adult germ
      line stem cells (maGSCs), are currently unknown. Here, we analyzed the expression
      of apoptosis-related genes using OligoGEArray in undifferentiated maGSCs and ESCs
      and identified a similar set of genes expressed in both cell types. We detected
      the expression of intrinsic, but not extrinsic, apoptotic pathway genes in both
      cell types. Further, we found that apoptosis-related gene expression patterns of
      differentiated ESCs and maGSCs are identical to each other. Comparative analysis
      revealed that several pro- and anti-apoptotic genes are expressed specifically in
      pluripotent cells, but markedly downregulated in the differentiated counterparts
      of these cells. Activation of the intrinsic apoptotic pathway cause approximately
      ~35% of both ESCs and maGSCs to adopt an early-apoptotic phenotype. Moreover, we
      performed transcriptome studies using early-apoptotic cells to identify novel
      pluripotency- and apoptosis-related genes. From these transcriptome studies, we
      selected Fgf4 (Fibroblast growth factor 4) and Mnda (Myeloid cell nuclear
      differentiating antigen), which are highly downregulated in early-apoptotic
      cells, as novel candidates and analyzed their roles in apoptosis and genotoxicity
      responses in ESCs. Collectively, our results show the existence of common
      molecular mechanisms for maintaining the pristine stem cell pool of both ESCs and
      maGSCs.

PMID- 23145005
TI  - Gamma-glutamyltransferase level and risk of hypertension: a systematic review and
      meta-analysis.
AB  - BACKGROUND: Several prospective observational studies suggest that gamma
      glutamyltransferase(GGT) level is positively associated with risk of
      hypertension. However, these studies draw inconsistent conclusions. Therefore, we
      conducted a systematic review and meta-analysis to evaluate the exact association
      between GGT level and subsequent development of hypertension. METHODS: We
      searched Pubmed, Embase, and Science Citation Index (ISI Web of Science) for
      prospective cohort studies examining the association between GGT level and
      hypertension. Then, pooled effect estimates (RRs) for the association between GGT
      level and hypertension were calculated. RESULTS: A total of 13 prospective cohort
      studies including 43314 participants and 5280 cases of hypertension were
      included. The pooled RR of hypertension was 1.94(95%CI: 1.55-2.43; P<0.001) when
      comparing the risk of hypertension between the highest versus lowest category of
      GGT levels. Moreover, the risk of hypertension increased by 23% (summary RR:
      1.23; 95%CI: 1.13-1.32; P<0.001) per 1 SD logGGT increment. Subgroup analyses
      showed significant positive associations in each subgroup except in ?160/95
      subgroup (RR: 2.56, 95%CI: 0.87-7.54; P = 0.088) and nondrinkers subgroup (RR:
      1.76, 95%CI: 0.88-3.53; P = 0.113). Sensitivity analyses showed no single study
      significantly affects the pooled RRs. No publication bias was found in our meta
      analysis. CONCLUSIONS: GGT level is positively associated with the development of
      hypertension. Further studies are needed to confirm our findings and elucidate
      the exact mechanisms between GGT level and the incidence of hypertension.

PMID- 23145004
TI  - Clinical value of prognosis gene expression signatures in colorectal cancer: a
      systematic review.
AB  - INTRODUCTION: The traditional staging system is inadequate to identify those
      patients with stage II colorectal cancer (CRC) at high risk of recurrence or with
      stage III CRC at low risk. A number of gene expression signatures to predict CRC
      prognosis have been proposed, but none is routinely used in the clinic. The aim
      of this work was to assess the prediction ability and potential clinical
      usefulness of these signatures in a series of independent datasets. METHODS: A
      literature review identified 31 gene expression signatures that used gene
      expression data to predict prognosis in CRC tissue. The search was based on the
      PubMed database and was restricted to papers published from January 2004 to
      December 2011. Eleven CRC gene expression datasets with outcome information were
      identified and downloaded from public repositories. Random Forest classifier was
      used to build predictors from the gene lists. Matthews correlation coefficient
      was chosen as a measure of classification accuracy and its associated p-value was
      used to assess association with prognosis. For clinical usefulness evaluation,
      positive and negative post-tests probabilities were computed in stage II and III
      samples. RESULTS: Five gene signatures showed significant association with
      prognosis and provided reasonable prediction accuracy in their own training
      datasets. Nevertheless, all signatures showed low reproducibility in independent
      data. Stratified analyses by stage or microsatellite instability status showed
      significant association but limited discrimination ability, especially in stage
      II tumors. From a clinical perspective, the most predictive signatures showed a
      minor but significant improvement over the classical staging system. CONCLUSIONS:
      The published signatures show low prediction accuracy but moderate clinical
      usefulness. Although gene expression data may inform prognosis, better strategies
      for signature validation are needed to encourage their widespread use in the
      clinic.

PMID- 23145006
TI  - Otx2 is involved in the regional specification of the developing retinal pigment
      epithelium by preventing the expression of sox2 and fgf8, factors that induce
      neural retina differentiation.
AB  - The retinal pigment epithelium (RPE) shares its developmental origin with the
      neural retina (NR). When RPE development is disrupted, cells in the presumptive
      RPE region abnormally differentiate into NR-like cells. Therefore, the prevention
      of NR differentiation in the presumptive RPE area seems to be essential for
      regionalizing the RPE during eye development. However, its molecular mechanisms
      are not fully understood. In this study, we conducted a functional inhibition of
      a transcription factor Otx2, which is required for RPE development, using early
      chick embryos. The functional inhibition of Otx2 in chick eyes, using a
      recombinant gene encoding a dominant negative form of Otx2, caused the outer
      layer of the optic cup (the region forming the RPE, when embryos normally
      develop) to abnormally form an ectopic NR. In that ectopic NR, the
      characteristics of the RPE did not appear and NR markers were ectopically
      expressed. Intriguingly, the repression of Otx2 function also caused the ectopic
      expression of Fgf8 and Sox2 in the outer layer of the optic cup (the presumptive
      RPE region of normally developing eyes). These two factors are known to be
      capable of inducing NR cell differentiation in the presumptive RPE region, and
      are not expressed in the normally developing RPE region. Here, we suggest that
      Otx2 prevents the presumptive RPE region from forming the NR by repressing the
      expression of both Fgf8 and Sox2 which induce the NR cell fate.

PMID- 23145007
TI  - Plasma clot lysis time and its association with cardiovascular risk factors in
      black Africans.
AB  - Studies in populations of European descent show longer plasma clot lysis times
      (CLT) in patients with cardiovascular disease (CVD) than in controls. No data are
      available on the association between CVD risk factors and fibrinolytic potential
      in black Africans, a group undergoing rapid urbanisation with increased CVD
      prevalence. We investigated associations between known CVD risk factors and CLT
      in black Africans and whether CLTs differ between rural and urban participants in
      light of differences in CVD risk.Data from 1000 rural and 1000 urban apparently
      healthy black South Africans (35-60 years) were cross-sectionally
      analysed.Increased PAI-1(act), BMI, HbA1c, triglycerides, the metabolic syndrome,
      fibrinogen concentration, CRP, female sex and positive HIV status were associated
      with increased CLTs, while habitual alcohol consumption associated with decreased
      CLT. No differences in CLT were found between age and smoking categories,
      contraceptive use or hyper- and normotensive participants. Urban women had longer
      CLT than rural women while no differences were observed for men.CLT was
      associated with many known CVD risk factors in black Africans. Differences were
      however observed, compared to data from populations of European descent available
      in the literature, suggesting possible ethnic differences. The effect of
      urbanisation on CLT is influenced by traditional CVD risk factors and their
      prevalence in urban and rural communities.

PMID- 23145008
TI  - Chaos of Wolbachia sequences inside the compact fig syconia of Ficus benjamina
      (Ficus: moraceae).
AB  - Figs and fig wasps form a peculiar closed community in which the Ficus tree
      provides a compact syconium (inflorescence) habitat for the lives of a complex
      assemblage of Chalcidoid insects. These diverse fig wasp species have intimate
      ecological relationships within the closed world of the fig syconia. Previous
      surveys of Wolbachia, maternally inherited endosymbiotic bacteria that infect
      vast numbers of arthropod hosts, showed that fig wasps have some of the highest
      known incidences of Wolbachia amongst all insects. We ask whether the
      evolutionary patterns of Wolbachia sequences in this closed syconium community
      are different from those in the outside world. In the present study, we sampled
      all 17 fig wasp species living on Ficus benjamina, covering 4 families, 6
      subfamilies, and 8 genera of wasps. We made a thorough survey of Wolbachia
      infection patterns and studied evolutionary patterns in wsp (Wolbachia Surface
      Protein) sequences. We find evidence for high infection incidences, frequent
      recombination between Wolbachia strains, and considerable horizontal transfer,
      suggesting rapid evolution of Wolbachia sequences within the syconium community.
      Though the fig wasps have relatively limited contact with outside world,
      Wolbachia may be introduced to the syconium community via horizontal transmission
      by fig wasps species that have winged males and visit the syconia earlier.

PMID- 23145009
TI  - The current waist circumference cut point used for the diagnosis of metabolic
      syndrome in sub-Saharan African women is not appropriate.
AB  - The waist circumference cut point for diagnosing the metabolic syndrome in sub
      Saharan African subjects is based on that obtained from studies in European
      populations. The aim of this study was to measure the prevalence of obesity and
      related metabolic disorders in an urban population of African females, a group at
      high risk for such diseases, and to determine the appropriate waist cut point for
      diagnosing the metabolic syndrome. Anthropometry and fasting lipid, glucose and
      insulin levels were measured in a cohort of 1251 African females participating in
      the Birth to Twenty cohort study in Soweto, Johannesburg. The waist circumference
      cut points for diagnosing metabolic syndrome (as defined using the new harmonised
      guidelines), insulin resistance, dysglycaemia, hypertension and dyslipidaemia
      were obtained using receiver operator characteristic curve analysis. The
      prevalence of obesity, type 2 diabetes and metabolic syndrome were 50.1%, 14.3%
      and 42.1%, respectively. The appropriate waist cut point for diagnosing metabolic
      syndrome was found to be 91.5 cm and was similar to the cuts points obtained for
      detecting increased risk of insulin resistance (89.0 cm), dysglycaemia (88.4 cm),
      hypertension (90.1 cm), hypo-high density lipoproteinaemia (87.6 cm) and hyper
      low density lipoproteinaemia (90.5 cm). The present data demonstrates that urban,
      African females have a high prevalence of obesity and related disorders and the
      waist cut point currently recommended for the diagnosis of the metabolic syndrome
      (80.0 cm) in this population should be increased to 91.5 cm. This latter finding
      demonstrates a clear ethnic difference in the relationship between abdominal
      adiposity and metabolic disease risk. The similar waist cut points identified for
      the detection of the individual components of the metabolic syndrome and related
      cardiovascular risk factors demonstrates that the risk for different metabolic
      diseases increases at the same level of abdominal adiposity suggesting a common
      aetiological pathway.

PMID- 23145010
TI  - The Australian baby bonus maternity payment and birth characteristics in Western
      Australia.
AB  - BACKGROUND: The Australian baby bonus maternity payment introduced in 2004 has
      been reported to have successfully increased fertility rates in Australia. We
      aimed to investigate the influence of the baby bonus on maternal demographics and
      birth characteristics in Western Australia (WA). METHODS AND FINDINGS: This study
      included 200,659 birth admissions from WA during 2001-2008, identified from
      administrative birth and hospital data-systems held by the WA Department of
      Health. We estimated average quarterly birth rates after the baby bonus
      introduction and compared them with expected rates had the policy not occurred.
      Rate and percentage differences (including 95% confidence intervals) were
      estimated separately by maternal demographics and birth characteristics. WA birth
      rates increased by 12.8% following the baby bonus implementation with the
      greatest increase being in mothers aged 20-24 years (26.3%, 95%CI = 22.0,30.6),
      mothers having their third (1.6%, 95%CI = 0.9,2.4) or fourth child (2.2%, 95%CI =
      2.1,2.4), mothers living in outer regional and remote areas (32.4%, 95%CI =
      30.2,34.6), mothers giving birth as public patients (1.5%, 95%CI = 1.3,1.8), and
      mothers giving birth in public hospitals (3.5%, 95%CI = 2.6,4.5). Interestingly,
      births to private patients (-4.3%, 95%CI = -4.8,-3.7) and births in private
      hospitals (-6.3%, 95%CI = -6.8,-5.8) decreased following the policy
      implementation. CONCLUSIONS: The introduction of the baby bonus maternity payment
      may have served as an incentive for women in their early twenties and mothers
      having their third or fourth child and may have contributed to the ongoing
      pressure and staff shortages in Australian public hospitals, particularly those
      in outer regional and remote areas.

PMID- 23145011
TI  - Aberrant resting-state corticostriatal functional connectivity in cirrhotic
      patients with hyperintense globus pallidus on T1-weighted MR imaging.
AB  - Neurobiological and neuroimaging studies have emphasized the structural and
      functional alterations in the striatum of cirrhotic patients, but alterations in
      the functional connections between the striatum and other brain regions have not
      yet been explored. Of note, manganese accumulation in the nervous system,
      frequently reflected by hyperintensity at the bilateral globus pallidus (GP) on
      T1-weighted imaging, has been considered a factor affecting the striatal and
      cortical functions in hepatic decompensation. We employed resting-state
      functional magnetic resonance imaging to analyze the temporal correlation between
      the striatum and the remaining brain regions using seed-based correlation
      analyses. The two-sample t-test was conducted to detect the differences in
      corticostriatal connectivity between 44 cirrhotic patients with hyperintensity at
      the bilateral GP and 20 healthy controls. Decreased connectivity of the caudate
      was detected in the anterior/middle cingulate gyrus, and increased connectivity
      of the caudate was found in the left motor cortex. A reduction in functional
      connectivity was found between the putamen and several regions, including the
      anterior cingulate gyrus, right insular lobe, inferior frontal gyrus, left
      parahippocampal gyrus, and anterior lobe of the right cerebellum; increased
      connectivity was detected between the putamen and right middle temporal gyrus.
      There were significant correlations between the corticostriatal connectivity and
      neuropsychological performances in the patient group, but not between the
      striatal connectivity and GP signal intensity. These alterations in the
      corticostriatal functional connectivity suggested the abnormalities in the
      intrinsic brain functional organiztion among the cirrhotic patients with
      manganese deposition, and may be associated with development of metabolic
      encephalopathy. The manganese deposition in nervous system, however, can not be
      an independent factor predicting the resting-state brain dysfunction in real
      time.

PMID- 23145012
TI  - Colorimetric grading scale can promote the standardization of experiential and
      sensory evaluation in quality control of traditional Chinese medicines.
AB  - Experiential and sensory evaluation is an ancient method that remains important
      in the current quality control system of Traditional Chinese Medicines (TCMs).
      The process is rapid and convenient when evaluating the quality of crude
      materials in TCM markets. However, sensory evaluation has been met with
      skepticism because it is mainly based on experience and lacks a scientific basis.
      In this study, rhubarb was selected to demonstrate how color-based sensory
      evaluation could differentiate the quality of herbal medicines objectively. The
      colors of the rhubarb samples, expressed as RGB values, were obtained from
      different parts and forms of the plant, including the plant's surface, fracture
      surface color, and a powdered form with or without treatment with a color
      developing reagent. We first divided the rhubarb samples into three grades based
      on the total content of five hydroxyanthraquinone derivatives, the major
      pharmacological components in rhubarb. Then, a three-layer back-propagation
      artificial neural network (BP-ANN), calibrated with selected training samples,
      was used to correlate the quality of the rhubarb with its color. The color of the
      rhubarb powder after coloration attained the highest accuracy (92.3%) in
      predicting the quality grade of the test samples with the established artificial
      neural networks. Finally, a standardized colorimetric grading scale was created
      based on the spatial distribution of the rhubarb samples in a two-dimensional
      chromaticity diagram according to the colors of the powdered rhubarb after color
      enhancement. By comparing the color between the scale and the tested samples,
      similar to performing a pH test with indicator paper, subjects without sensory
      evaluation experience could quickly determine the quality grade of rhubarb. This
      work illustrates the technical feasibility of the color-based grading of rhubarb
      quality and offers references for quantifying and standardizing the sensory
      evaluation of TCMs, foods and other products.

PMID- 23145013
TI  - Circadian regulation of food-anticipatory activity in molecular clock-deficient
      mice.
AB  - In the mammalian brain, the suprachiasmatic nucleus (SCN) of the anterior
      hypothalamus is considered to be the principal circadian pacemaker, keeping the
      rhythm of most physiological and behavioral processes on the basis of light/dark
      cycles. Because restriction of food availability to a certain time of day elicits
      anticipatory behavior even after ablation of the SCN, such behavior has been
      assumed to be under the control of another circadian oscillator. According to
      recent studies, however, mutant mice lacking circadian clock function exhibit
      normal food-anticipatory activity (FAA), a daily increase in locomotor activity
      preceding periodic feeding, suggesting that FAA is independent of the known
      circadian oscillator. To investigate the molecular basis of FAA, we examined
      oscillatory properties in mice lacking molecular clock components. Mice with SCN
      lesions or with mutant circadian periods were exposed to restricted feeding
      schedules at periods within and outside circadian range. Periodic feeding led to
      the entrainment of FAA rhythms only within a limited circadian range. Cry1(-/-)
      mice, which are known to be a "short-period mutant," entrained to a shorter
      period of feeding cycles than did Cry2(-/-) mice. This result indicated that the
      intrinsic periods of FAA rhythms are also affected by Cry deficiency. Bmal1(-/-)
      mice, deficient in another essential element of the molecular clock machinery,
      exhibited a pre-feeding increase of activity far from circadian range, indicating
      a deficit in circadian oscillation. We propose that mice possess a food
      entrainable pacemaker outside the SCN in which canonical clock genes such as
      Cry1, Cry2 and Bmal1 play essential roles in regulating FAA in a circadian
      oscillatory manner.

PMID- 23145015
TI  - Harmonization of the practice of independent ethics committees in Italy: project
      E-submission.
AB  - AIM: The high variability of "centre-specific" documentation required by
      Independent Ethics Committee (IEC) plays a role in the time required for
      activation of participating centres of multicentre clinical trials. This study
      (a) provides a picture of the different activities, structural requirements and
      resources dedicated to the operation of the local IEC in Italy; (b) defines a
      detailed list of "centre-specific" documents considered as essential by the IEC
      for issuing its opinion and (c) suggests a "single document" to reduce the
      variability of the "centre-specific" documents required by the IEC. METHODOLOGY:
      Two surveys were conducted through the portal of National Monitoring Centre of
      Clinical Trials (https://oss-sper-clin.agenziafarmaco.it/). The first survey
      focused on the local IEC resources and on the "centre-specific" documentation
      that local IEC required from the Sponsor and local Principal Investigator (PI).
      The second focused on "single document" required in the form of statements from
      the Sponsor and the PI. Answers were discussed and extended during regular
      scheduled teleconferences and plenary meeting. PRINCIPAL FINDINGS: From
      22/07/2009 to 15/12/2009, and from 19/04/2010 to 14/05/2010, 131 and 125 IECs
      responded to the first and the second surveys, respectively. 67% and 51% of IECs
      consider the structural requirements and the staff dedicated to the activity of
      the IECs as sufficient, respectively. Most of the IECs consider the "centre
      specific" documentation as necessary for issuing the opinion, and a high
      percentage of IECs consider the proposed documentation as acceptable in
      substitution to any other "centre-specific" documentation already in use.
      CONCLUSIONS: The harmonization of IECs practice in Italy is the first step to
      facilitate multicentre clinical trials. Similar efforts should be directed to
      reduce the total number of IECs and to standardize clinical trials approval
      procedures, focusing on administrative procedures as well.

PMID- 23145014
TI  - Cellular expression profile for interstitial cells of cajal in bladder - a cell
      often misidentified as myocyte or myofibroblast.
AB  - BACKGROUND: Interstitial cells of Cajal (ICC) have been identified in urinary
      bladder of several species, but their presence in mice remains uncertain.
      Meanwhile, dozens of reports indicate that dysregulation of connexin 43 plays an
      important role in bladder overactivity, but its localization has not been clearly
      defined, with reports of expression in either the smooth muscle or in
      myofibroblasts. We recently identified a population of ectonucleoside
      triphosphate diphosphohydrolase 2 (NTPDase2) positive cells that resemble ICC and
      are distinct from smooth muscle, fibroblasts, myofibroblasts and neurons. Thus we
      sought to define more clearly the molecular signature of ICC and in doing so
      resolve some of these uncertainties. PRINCIPLE FINDINGS: Immunofluorescent
      localization revealed that NTPDase2-positive cells lie closely adjacent to smooth
      muscle but are separate from them. NTPDase2 positive cells exhibited co
      localization with the widely accepted ICC marker - c-kit. They were further shown
      to co-localize with other ICC markers CD34 and Ano1, but not with mast cell
      marker tryptase. Significantly, they show convincing co-localization with
      connexin 43, which was not present in smooth muscle. The identity of these cells
      as ICC was further confirmed by the presence of three mesenchymal markers -
      vimentin, desmin, and PDGFbeta receptor, which indicates their mesenchymal
      origin. Finally, we observed for the first time, the presence of
      merlin/neurofibromin 2 in ICC. Normally considered a neuronal protein, the
      presence of merlin suggests ICC in bladder may have a role in neurotransmission.
      CONCLUSIONS: NTPDase2 positive cells in mice bladder are ICC, which can be
      defined by the presence of c-Kit, CD34, Ano1, NTPDase2, connexin 43, vimentin,
      desmin, PDGFbeta receptor and merlin/NF2. These data establish a definitive
      molecular expression profile, which can be used to assist in explorations of
      their functional roles, and the presence of NTPDase2 suggests that purinergic
      signaling plays a role in regulation of ICC function.

PMID- 23145016
TI  - Biomimetic and live medusae reveal the mechanistic advantages of a flexible bell
      margin.
AB  - Flexible bell margins are characteristic components of rowing medusan
      morphologies and are expected to contribute towards their high propulsive
      efficiency. However, the mechanistic basis of thrust augmentation by flexible
      propulsors remained unresolved, so the impact of bell margin flexibility on
      medusan swimming has also remained unresolved. We used biomimetic robotic
      jellyfish vehicles to elucidate that propulsive thrust enhancement by flexible
      medusan bell margins relies upon fluid dynamic interactions between entrained
      flows at the inflexion point of the exumbrella and flows expelled from under the
      bell. Coalescence of flows from these two regions resulted in enhanced fluid
      circulation and, therefore, thrust augmentation for flexible margins of both
      medusan vehicles and living medusae. Using particle image velocimetry (PIV) data
      we estimated pressure fields to demonstrate a mechanistic basis of enhanced flows
      associated with the flexible bell margin. Performance of vehicles with flexible
      margins was further enhanced by vortex interactions that occur during bell
      expansion. Hydrodynamic and performance similarities between robotic vehicles and
      live animals demonstrated that the propulsive advantages of flexible margins
      found in nature can be emulated by human-engineered propulsors. Although medusae
      are simple animal models for description of this process, these results may
      contribute towards understanding the performance of flexible margins among other
      animal lineages.

PMID- 23145017
TI  - DNA-interactive properties of crotamine, a cell-penetrating polypeptide and a
      potential drug carrier.
AB  - Crotamine, a 42-residue polypeptide derived from the venom of the South American
      rattlesnake Crotalus durissus terrificus, has been shown to be a cell-penetrating
      protein that targets chromosomes, carries plasmid DNA into cells, and shows
      specificity for actively proliferating cells. Given this potential role as a
      nucleic acid-delivery vector, we have studied in detail the binding of crotamine
      to single- and double-stranded DNAs of different lengths and base compositions
      over a range of ionic conditions. Agarose gel electrophoresis and ultraviolet
      spectrophotometry analysis indicate that complexes of crotamine with long-chain
      DNAs readily aggregate and precipitate at low ionic strength. This aggregation,
      which may be important for cellular uptake of DNA, becomes less likely with
      shorter chain length. 25-mer oligonucleotides do not show any evidence of such
      aggregation, permitting the determination of affinities and size via fluorescence
      quenching experiments. The polypeptide binds non-cooperatively to DNA, covering
      about 5 nucleotide residues when it binds to single (ss) or (ds) double stranded
      molecules. The affinities of the protein for ss- vs. ds-DNA are comparable, and
      inversely proportional to salt levels. Analysis of the dependence of affinity on
      [NaCl] indicates that there are a maximum of ~3 ionic interactions between the
      protein and DNA, with some of the binding affinity attributable to non-ionic
      interactions. Inspection of the three-dimensional structure of the protein
      suggests that residues 31 to 35, Arg-Trp-Arg-Trp-Lys, could serve as a potential
      DNA-binding site. A hexapeptide containing this sequence displayed a lower DNA
      binding affinity and salt dependence as compared to the full-length protein,
      likely indicative of a more suitable 3D structure and the presence of accessory
      binding sites in the native crotamine. Taken together, the data presented here
      describing crotamine-DNA interactions may lend support to the design of more
      effective nucleic acid drug delivery vehicles which take advantage of crotamine
      as a carrier with specificity for actively proliferating cells.

PMID- 23145018
TI  - Allorecognition triggers autophagy and subsequent necrosis in the cnidarian
      Hydractinia symbiolongicarpus.
AB  - Transitory fusion is an allorecognition phenotype displayed by the colonial
      hydroid Hydractinia symbiolongicarpus when interacting colonies share some, but
      not all, loci within the allorecognition gene complex (ARC). The phenotype is
      characterized by an initial fusion followed by subsequent cell death resulting in
      separation of the two incompatible colonies. We here characterize this cell death
      process using scanning electron microscopy (SEM), transmission electron
      microscopy (TEM), and continuous in vivo digital microscopy. These techniques
      reveal widespread autophagy and subsequent necrosis in both colony and grafted
      polyp assays. Terminal deoxynucleotidyl transferase dUTP nick end labeling
      (TUNEL) assays and ultrastructural observations revealed no evidence of
      apoptosis. Pharmacological inhibition of autophagy using 3-methyladenine (3-MA)
      completely suppressed transitory fusion in vivo in colony assays. Rapamycin did
      not have a significant effect in the same assays. These results establish the
      hydroid allorecognition system as a novel model for the study of cell death.

PMID- 23145019
TI  - Maternal deprivation exacerbates the response to a high fat diet in a sexually
      dimorphic manner.
AB  - Maternal deprivation (MD) during neonatal life has diverse long-term effects,
      including affectation of metabolism. Indeed, MD for 24 hours during the neonatal
      period reduces body weight throughout life when the animals are maintained on a
      normal diet. However, little information is available regarding how this early
      stress affects the response to increased metabolic challenges during postnatal
      life. We hypothesized that MD modifies the response to a high fat diet (HFD) and
      that this response differs between males and females. To address this question,
      both male and female Wistar rats were maternally deprived for 24 hours starting
      on the morning of postnatal day (PND) 9. Upon weaning on PND22 half of each group
      received a control diet (CD) and the other half HFD. MD rats of both sexes had
      significantly reduced accumulated food intake and weight gain compared to
      controls when raised on the CD. In contrast, when maintained on a HFD energy
      intake and weight gain did not differ between control and MD rats of either sex.
      However, high fat intake induced hyperleptinemia in MD rats as early as PND35,
      but not until PND85 in control males and control females did not become
      hyperleptinemic on the HFD even at PND102. High fat intake stimulated
      hypothalamic inflammatory markers in both male and female rats that had been
      exposed to MD, but not in controls. Reduced insulin sensitivity was observed only
      in MD males on the HFD. These results indicate that MD modifies the metabolic
      response to HFD intake, with this response being different between males and
      females. Thus, the development of obesity and secondary complications in response
      to high fat intake depends on numerous factors.

PMID- 23145020
TI  - RhoC regulates the proliferation of gastric cancer cells through interaction with
      IQGAP1.
AB  - Our previous research results showed that both Ras homolog family member C (RhoC)
      and IQ-domain GTPase-activating protein 1 (IQGAP1) were over-expressed in gastric
      cancer tissues and cells, but their role in tumorigenensis has not been addressed
      clearly. Herein we reported the proliferation stimulating effect of RhoC and
      IQGAP1 on gastric cancer cells and the interaction between two proteins in
      regulating the proliferation of gastric cancer cells. Plasmids and viral
      constructs encoding target siRNA and DNA were used to alter the expression of
      RhoC and IQGAP1. MTT method and BrdU incorporation assay were used for analyzing
      the effect of RhoC and different structures of IQGAP1 on proliferation. Protein
      levels of IQGAP1 and RhoC in cell lines were detected by Western blotting.
      Immunofluorescence and Co-Immunoprecipitation assays were applied to investigate
      the localization and binding between RhoC and IQGAP1. The results showed that
      RhoC, IQGAP1 and the C-terminal fragment of IQGAP1 significantly stimulated the
      proliferation of gastric cancer cells, and enhanced the expression of cyclin E
      and cyclin D1. By contrast, reduction of endogenous IQGAP1 or RhoC by siRNA
      attenuated cell proliferation. The depletion of IQGAP1 expression by siRNA
      significantly blocked the proliferative activity of constitutively active RhoC,
      while RhoC silencing by siRNA had no effect on IQGAP1-induced proliferation in
      gastric cancer cells. Co-immunoprecipitation and Immunofluorescence assays showed
      that RhoC and IQGAP1 bound each other. In conclusion, our results suggest that
      RhoC stimulates the proliferation of gastric cancer cells through recruiting
      IQGAP1 as an effector.

PMID- 23145021
TI  - Urine from treated cattle drives selection for cephalosporin resistant
      Escherichia coli in soil.
AB  - The U.S. Food and Drug Administration recently issued new rules for using
      ceftiofur in food animals in part because of an increasing prevalence of enteric
      bacteria that are resistant to 3(rd)-generation cephalosporins. Parenteral
      ceftiofur treatment, however, has limited effects on enteric bacteria so we
      tested the hypothesis that excreted ceftiofur metabolites exert significant
      selection pressure for ceftiofur-resistant Escherichia coli in soil. Test
      matrices were prepared by mixing soil with bovine feces and adding urine
      containing ceftiofur metabolites (CFM) (0 ppm, ~50 ppm and ~100 ppm). Matrices
      were incubated at 23 degrees C or 4 degrees C for variable periods of time after
      which residual CFM was quantified using a bioassay. Bla(CMY-2) plasmid-bearing
      ceftiofur resistant (cef(R)) E. coli and one-month old calves were used to study
      the selection effects of CFM and transmission of cef(R) bacteria from the
      environment back to animals. Our studies showed that urinary CFM (~13 ppm final
      concentration) is biologically degraded in soil within 2.7 days at 23 degrees C,
      but persists up to 23.3 days at 4 degrees C. Even short-term persistence in soil
      provides a >1 log(10) advantage to resistant E. coli populations, resulting in
      significantly prolonged persistence of these bacteria in the soil (~two months).
      We further show that resistant strains readily colonize calves by contact with
      contaminated bedding and without antibiotic selection pressure. Ceftiofur
      metabolites in urine amplify resistant E. coli populations and, if applicable to
      field conditions, this effect is far more compelling than reported selection in
      vivo after parenteral administration of ceftiofur. Because ceftiofur degradation
      is temperature dependent, these compounds may accumulate during colder months and
      this could further enhance selection as seasonal temperatures increase. If cost
      effective engineered solutions can be developed to limit ex vivo selection, this
      may limit proliferation for ceftiofur resistant enteric bacteria while preserving
      the ability to use this important antibiotic in food animal production.

PMID- 23145022
TI  - Tetrahymena: an alternative model host for evaluating virulence of Aeromonas
      strains.
AB  - An easier assessment model would be helpful for high-throughput screening of
      Aeromonas virulence. The previous study indicated the potential of Tetrahymena as
      a permissive model to examine virulence of Aeromonas hydrophila. Here our aim was
      to assess virulence of Aeromonas spp. using two model hosts, a zebrafish assay
      and Tetrahymena-Aeromonas co-culture, and to examine whether data from the
      Tetrahymena thermophila model reflects infections in the well-established animal
      model. First, virulence of 39 Aeromonas strains was assessed by determining the
      50% lethal dose (LD(50)) in zebrafish. LD(50) values ranging from 1.3*10(2) to
      3.0*10(7) indicated that these strains represent a high to moderate degree of
      virulence and could be useful to assess virulence in the Tetrahymena model. In
      Tetrahymena-Aeromonas co-culture, we evaluated the virulence of Aeromonas by
      detecting relative survival of Aeromonas and Tetrahymena. An Aeromonas isolate
      was considered virulent when its relative survival was greater than 60%, while
      the Aeromonas isolate was considered avirulent if its relative survival was below
      40%. When relative survival of T. thermophila was lower than 40% after co-culture
      with an Aeromonas isolate, the bacterial strain was regarded as virulent. In
      contrast, the strain was classified as avirulent if relative survival of T.
      thermophila was greater than 50%. Encouragingly, data from the 39 Aeromonas
      strains showed good correlation in zebrafish and Tetrahymena-Aeromonas co-culture
      models. The results provide sufficient data to demonstrate that Tetrahymena can
      be a comparable alternative to zebrafish for determining the virulence of
      Aeromonas isolates.

PMID- 23145023
TI  - Appraising hospital performance by using the JCHAO/CMS quality measures in
      Southern Italy.
AB  - OBJECTIVES: The main objective of the present study was to estimate the uptake to
      quality indicators that reflect the current evidence-based recommendations and
      guidelines. METHODS: A retrospective review of medical records of patients
      admitted to two hospitals in the South of Italy was conducted. For the purposes
      of the analysis, a sets of quality indicators has been used from the Joint
      Commission on Accreditation of Hospital Organizations and Centers for Medicare &
      Medicaid Services. Four areas of care were selected: acute myocardial infarction
      (AMI), heart failure (HF), pneumonia (PN), and surgical care improvement project
      (SCIP). Frequency or median was calculated, as appropriate, for each indicator. A
      composite score was calculated to estimate the overall performance for each area
      of care. RESULTS: A total of 1772 medical records were reviewed. The adherence
      rates showed a wide-ranging variability among the selected indicators. The use of
      aspirin and angiotensin-converting enzyme inhibitor (ACEI) or angiotensin
      receptor blocker (ARB) for AMI, the use of ACEI or ARB for HF, the use of
      appropriate thromboembolism prophylaxis and appropriate hair removal for surgical
      patients almost approached optimal adherence. At the other extreme, rates
      regarding adherence to smoking-cessation counseling in AMI and HF patients,
      discharge instructions in HF patients, and influenza and pneumococcal vaccination
      in pneumonia patients were noticeably intangible. Overall, the recommended
      processes of care among eligible patients were provided in 70% for AMI, in 32.4%
      for HF, in 46.4% for PN, and in 46% for SCIP. CONCLUSIONS: The results show that
      there is still substantial work that lies ahead on the way to improve the uptake
      to evidence-based processes of care. Improvement initiatives should be focused
      more on domains of healthcare than on specific conditions, especially on the area
      of preventive care.

PMID- 23145025
TI  - Design of pH sensitive binding proteins from the hyperthermophilic Sso7d
      scaffold.
AB  - We have engineered pH sensitive binding proteins for the Fc portion of human
      immunoglobulin G (hIgG) (hFc) using two different strategies - histidine scanning
      and random mutagenesis. We obtained an hFc-binding protein, Sso7d-hFc, through
      mutagenesis of the Sso7d protein from the hyperthermophilic archaeon Sulfolobus
      solfataricus; Sso7d-hFc was isolated from a combinatorial library of Sso7d
      mutants using yeast surface display. Subsequently, we identified a pH sensitive
      mutant, Sso7d-his-hFc, through systematic evaluation of Sso7d-hFc mutants
      containing single histidine substitutions. In parallel, we also developed a yeast
      display screening strategy to isolate a different pH sensitive hFc binder, Sso7d
      ev-hFc, from a library of mutants obtained by random mutagenesis of a pool of hFc
      binders. In contrast to Sso7d-hFc, both Sso7d-his-hFc and Sso7d-ev-hFc have a
      higher binding affinity for hFc at pH 7.4 than at pH 4.5. The Sso7d-mutant hFc
      binders can be recombinantly expressed at high yield in E. coli and are monomeric
      in solution. They bind an epitope in the CH3 domain of hFc that has high sequence
      homology in all four hIgG isotypes (hIgG(1-4)), and recognize hIgG(1-4) as well
      as deglycosylated hIgG in western blotting assays. pH sensitive hFc binders are
      attractive candidates for use in chromatography, to achieve elution of IgG under
      milder pH conditions. However, the surface density of immobilized hFc binders, as
      well as the avidity effect arising from the multivalent interaction of dimeric
      hFc with the capture surface, influences the pH dependence of dissociation from
      the capture surface. Therefore, further studies are needed to evaluate if the
      Sso7d mutants identified in this study are indeed useful as affinity ligands in
      chromatography.

PMID- 23145024
TI  - Pgc-1alpha overexpression downregulates Pitx3 and increases susceptibility to
      MPTP toxicity associated with decreased Bdnf.
AB  - Multiple mechanisms likely contribute to neuronal death in Parkinson's disease
      (PD), including mitochondrial dysfunction and oxidative stress. Peroxisome
      proliferator-activated receptor gamma co-activator-1 alpha (PGC-1alpha)
      positively regulates the expression of genes required for mitochondrial
      biogenesis and the cell's antioxidant responses. Also, expression of PGC-1alpha
      regulated genes is low in substantia nigra (SN) neurons in early PD. Thus
      upregulation of PGC-1alpha is a candidate neuroprotective strategy in PD. Here,
      an adeno-associated virus (AAV) was used to induce unilateral overexpression of
      Pgc-1alpha, or a control gene, in the SN of wild-type C57BL/6CR mice. Three weeks
      after AAV administration, mice were treated with saline or MPTP. Overexpression
      of Pgc-1alpha in the SN induced expression of target genes, but unexpectedly it
      also greatly reduced the expression of tyrosine hydroxylase (Th) and other
      markers of the dopaminergic phenotype with resultant severe loss of striatal
      dopamine. Reduced Th expression was associated with loss of Pitx3, a
      transcription factor that is critical for the development and maintenance of
      dopaminergic cells. Expression of the neurotrophic factor Bdnf, which also is
      regulated by Pitx3, similarly was reduced. Overexpression of Pgc-1alpha also led
      to increased sensitivity to MPTP-induced death of Th+ neurons. Pgc-1alpha
      overexpression alone, in the absence of MPTP treatment, did not lead to cell loss
      in the SN or to loss of dopaminergic terminals. These data demonstrate that
      overexpression of Pgc-1alpha results in dopamine depletion associated with lower
      levels of Pitx3 and enhances susceptibility to MPTP. These data may have
      ramifications for neuroprotective strategies targeting overexpression of PGC
      1alpha in PD.

PMID- 23145026
TI  - A20 controls macrophage to elicit potent cytotoxic CD4(+) T cell response.
AB  - Emerging evidence indicates that CD4(+) T cells possess cytotoxic potential for
      tumor eradication and perforin/granzyme-mediated cytotoxicity functions as one of
      the important mechanisms for CD4(+) T cell-triggered cell killing. However, the
      critical issue is how the cytotoxic CD4(+) T cells are developed. During the
      course of our work that aims at promoting immunostimulation of APCs by inhibition
      of negative regulators, we found that A20-silenced Mf drastically induced
      granzyme B expression in CD4(+) T cells. As a consequence, the granzyme-highly
      expressing CD4(+) T cells exhibited a strong cytotoxic activity that restricted
      tumor development. We found that A20-silenced Mf activated cytotoxic CD4(+) T
      cells by MHC class-II restricted mechanism and the activation was largely
      dependent on enhanced production of IFN-gamma.

PMID- 23145027
TI  - Salvage liver transplantation for recurrent hepatocellular carcinoma within UCSF
      criteria after liver resection.
AB  - BACKGROUND: Salvage liver transplantation (SLT) is restricted to patients who
      develop hepatocellular carcinoma (HCC) recurrence within Milan criteria (MC).
      Little is known about outcomes for SLT in patients with recurrent HCC within
      University of California San Francisco (UCSF) criteria after liver resection
      (LR). METHODS: Between January 2001 and December 2011, 380 patients with HCC
      meeting UCSF criteria, 200 of which were resected (LR group) from a perspective
      of SLT in case of recurrence, and 180 directly underwent LT (PLT). We compared
      patient characteristics, perioperative and long-term outcomes between SLT and PLT
      groups. We also assessed the outcome of LR and PLT groups. RESULTS: Among the 200
      patients in LR group, 86 (43%) developed HCC recurrence and 15/86 (17%) of these
      patients presented HCC recurrence outside UCSF criteria. Only 39 of the 86
      patients underwent SLT, a transplantation rate of 45% of patients with HCC
      recurrence. Compared with PLT group, LR group showed lower overall survival rate
      (P = 0.005) and higher recurrence rate (P = 0.006). Although intraoperative blood
      loss and required blood transfusion were more frequent in SLT group, the
      perioperative mortality and posttransplant complications were similar in SLT and
      PLT groups. The overall survival and recurrence rates did not significantly
      differ between the two groups. When stratifying by graft type in the SLT group,
      overall survival and recurrence rates did not significantly differ between
      deceased donor LT (DDLT) and living donor LT (LDLT) groups. In the subgroup
      analysis by MC, similar results were observed between patients with recurrent HCC
      meeting MC and patients with recurrent HCC beyond MC but within UCSF criteria.
      CONCLUSION: Our single institution experience demonstrated that prior hepatectomy
      and SLT for recurrent HCC within UCSF criteria was feasible and SLT could achieve
      the same outcome as PLT.

PMID- 23145028
TI  - Constitutive beta-catenin signaling by the viral chemokine receptor US28.
AB  - Chronic activation of Wnt/beta-catenin signaling is found in a variety of human
      malignancies including melanoma, colorectal and hepatocellular carcinomas.
      Interestingly, expression of the HCMV-encoded chemokine receptor US28 in
      intestinal epithelial cells promotes intestinal neoplasia in transgenic mice,
      which is associated with increased nuclear accumulation of beta-catenin. In this
      study we show that this viral receptor constitutively activates beta-catenin and
      enhances beta-catenin-dependent transcription. Our data illustrate that this
      viral receptor does not activate beta-catenin via the classical Wnt/Frizzled
      signaling pathway. Analysis of US28 mediated signaling indicates the involvement
      of the Rho-Rho kinase (ROCK) pathway in the activation of beta-catenin. Moreover,
      cells infected with HCMV show significant increases in beta-catenin stabilization
      and signaling, which is mediated to a large extent by expression of US28. The
      modulation of the beta-catenin signal transduction pathway by a viral chemokine
      receptor provides alternative regulation of this pathway, with potential
      relevance for the development of colon cancer and virus-associated diseases.

PMID- 23145029
TI  - Intronic parent-of-origin dependent differential methylation at the Actn1 gene is
      conserved in rodents but is not associated with imprinted expression.
AB  - Parent-of-origin differential DNA methylation has been associated with regulation
      of the preferential expression of paternal or maternal alleles of imprinted
      genes. Based on this association, recent studies have searched for parent-of
      origin dependent differentially methylated regions in order to identify new
      imprinted genes in their vicinity. In a previous genome-wide analysis of mouse
      brain DNA methylation, we found a novel differentially methylated region in a CpG
      island located in the last intron of the alpha 1 Actinin (Actn1) gene. In this
      region, preferential methylation of the maternal allele was observed; however,
      there were no reports of imprinted expression of Actn1. Therefore, we have tested
      if differential methylation of this region is common to other tissues and species
      and affects the expression of Actn1. We have found that Actn1 differential
      methylation occurs in diverse mouse tissues. Moreover, it is also present in
      other murine rodents (rat), but not in the orthologous human region. In contrast,
      we have found no indication of an imprinted effect on gene expression of Actn1 in
      mice: expression is always biallelic regardless of sex, tissue type,
      developmental stage or isoform. Therefore, we have identified a novel parent-of
      origin dependent differentially methylated region that has no apparent
      association with imprinted expression of the closest genes. Our findings sound a
      cautionary note to genome-wide searches on the use of differentially methylated
      regions for the identification of imprinted genes and suggest that parent-of
      origin dependent differential methylation might be conserved for functions other
      that the control of imprinted expression.

PMID- 23145030
TI  - Elevated expression of KiSS-1 in placenta of Chinese women with early-onset
      preeclampsia.
AB  - Preeclampsia (PE) is a heterogeneous syndrome affecting 2% to 8% of all
      pregnancies and is the world's leading cause of fetal and maternal morbidity and
      mortality. In many cases of PE, shallow trophoblast invasion results in
      inappropriate maternal spiral artery remodeling and impaired placental function.
      Multiple genes have been implicated in trophoblast invasion, among which are KiSS
      1 and GPR54. The gene product of KiSS-1 is metastin, which is a ligand for the
      receptor GPR54. Both metastin and GPR54 are expressed in the placenta of normal
      pregnancy and have been implicated in modulating trophoblast invasion through
      inhibiting migration of trophoblast cells. We have previously reported that the
      expression level of KiSS-1 was higher in trophoblasts from women with
      preeclampsia as compared to normal controls. Here, using quantitative RT-PCR,
      Western blot analysis and immunohistochemistry, we extend our analysis to
      demonstrate that elevated KiSS-1 expression occurs only in early-onset
      preeclampsia (ePE) and not late-onset preeclampsia (lPE). However, no difference
      in the expression levels of GPR54 is observed between ePE, lPE, and normal
      controls. Further, we show that KiSS-1 expression is also increased in placenta
      of intrauterine death and birth asphyxia in comparison to normal newborns of ePE
      and lPE. Our findings suggest that aberrant upregulation of KiSS-1 expression may
      contribute to the underlying mechanism of ePE as well as birth asphyxia.

PMID- 23145031
TI  - The hepatitis B virus x protein inhibits thymine DNA glycosylase initiated base
      excision repair.
AB  - The hepatitis B virus (HBV) genome encodes the X protein (HBx), a ubiquitous
      transactivator that is required for HBV replication. Expression of the HBx
      protein has been associated with the development of HBV infection-related
      hepatocellular carcinoma (HCC). Previously, we generated a 3D structure of HBx by
      combined homology and ab initio in silico modelling. This structure showed a
      striking similarity to the human thymine DNA glycosylase (TDG), a key enzyme in
      the base excision repair (BER) pathway. To further explore this finding, we
      investigated whether both proteins interfere with or complement each other's
      functions. Here we show that TDG does not affect HBV replication, but that HBx
      strongly inhibits TDG-initiated base excision repair (BER), a major DNA repair
      pathway. Inhibition of the BER pathway may contribute substantially to the
      oncogenic effect of HBV infection.

PMID- 23145032
TI  - Identification of novel HIV 1--protease inhibitors: application of ligand and
      structure based pharmacophore mapping and virtual screening.
AB  - A combined ligand and structure-based drug design approach provides a synergistic
      advantage over either methods performed individually. Present work bestows a good
      assembly of ligand and structure-based pharmacophore generation concept. Ligand
      oriented study was accomplished by employing the HypoGen module of Catalyst in
      which we have translated the experimental findings into 3-D pharmacophore models
      by identifying key features (four point pharmacophore) necessary for interaction
      of the inhibitors with the active site of HIV-1 protease enzyme using a training
      set of 33 compounds belonging to the cyclic cyanoguanidines and cyclic urea
      derivatives. The most predictive pharmacophore model (hypothesis 1), consisting
      of four features, namely, two hydrogen bond acceptors and two hydrophobic, showed
      a correlation (r) of 0.90 and a root mean square of 0.71 and cost difference of
      56.59 bits between null cost and fixed cost. The model was validated using
      CatScramble technique, internal and external test set prediction. In the second
      phase of our study, a structure-based five feature pharmacophore hypothesis was
      generated which signifies the importance of hydrogen bond donor, hydrogen bond
      acceptors and hydrophobic interaction between the HIV-1 protease enzyme and its
      inhibitors. This work has taken a significant step towards the full integration
      of ligand and structure-based drug design methodologies as pharmacophoric
      features retrieved from structure-based strategy complemented the features from
      ligand-based study hence proving the accuracy of the developed models. The ligand
      based pharmacophore model was used in virtual screening of Maybridge and NCI
      compound database resulting in the identification of four structurally diverse
      druggable compounds with nM activities.

PMID- 23145033
TI  - Lentiviral transduction of CD34(+) cells induces genome-wide epigenetic
      modifications.
AB  - Epigenetic modifications may occur during in vitro manipulations of stem cells
      but these effects have remained unexplored in the context of cell and gene
      therapy protocols. In an experimental model of ex vivo gene modification for
      hematopoietic gene therapy, human CD34(+) cells were cultured shortly in the
      presence of cytokines then with a gene transfer lentiviral vector (LV) expected
      to transduce cells but to have otherwise limited biological effects on the cells.
      At the end of the culture, the population of cells remained largely similar at
      the phenotypic level but some epigenetic changes were evident. Exposure of
      CD34(+) cells to cytokines increased nuclear expression of epigenetic regulators
      SIRT1 or DNMT1 and caused genome-wide DNA methylation changes. Surprisingly, the
      LV caused additional and distinct effects. Large-scale genomic DNA methylation
      analysis showed that balanced methylation changes occurred in about 200 genes
      following culture of CD34(+) cells in the presence of cytokines but 900 genes
      were modified following addition of the LV, predominantly increasing CpG
      methylation. Epigenetic effects resulting from ex vivo culture and from the use
      of LV may constitute previously unsuspected sources of biological effects in stem
      cells and may provide new biomarkers to rationally optimize gene and cell therapy
      protocols.

PMID- 23145034
TI  - Human alpha(2)beta(1)(HI) CD133(+VE) epithelial prostate stem cells express low
      levels of active androgen receptor.
AB  - Stem cells are thought to be the cell of origin in malignant transformation in
      many tissues, but their role in human prostate carcinogenesis continues to be
      debated. One of the conflicts with this model is that cancer stem cells have been
      described to lack androgen receptor (AR) expression, which is of established
      importance in prostate cancer initiation and progression. We re-examined the
      expression patterns of AR within adult prostate epithelial differentiation using
      an optimised sensitive and specific approach examining transcript, protein and AR
      regulated gene expression. Highly enriched populations were isolated consisting
      of stem (alpha(2)beta(1)(HI) CD133(+VE)), transiently amplifying
      (alpha(2)beta(1)(HI) CD133(-VE)) and terminally differentiated
      (alpha(2)beta(1)(LOW) CD133(-VE)) cells. AR transcript and protein expression was
      confirmed in alpha(2)beta(1)(HI) CD133(+VE) and CD133(-VE) progenitor cells. Flow
      cytometry confirmed that median (+/-SD) fraction of cells expressing AR were 77%
      (+/-6%) in alpha(2)beta(1)(HI) CD133(+VE) stem cells and 68% (+/-12%) in
      alpha(2)beta(1)(HI) CD133(-VE) transiently amplifying cells. However, 3-fold
      lower levels of total AR protein expression (peak and median immunofluorescence)
      were present in alpha(2)beta(1)(HI) CD133(+VE) stem cells compared with
      differentiated cells. This finding was confirmed with dual immunostaining of
      prostate sections for AR and CD133, which again demonstrated low levels of AR
      within basal CD133(+VE) cells. Activity of the AR was confirmed in prostate
      progenitor cells by the expression of low levels of the AR regulated genes PSA,
      KLK2 and TMPRSS2. The confirmation of AR expression in prostate progenitor cells
      allows integration of the cancer stem cell theory with the established models of
      prostate cancer initiation based on a functional AR. Further study of specific AR
      functions in prostate stem and differentiated cells may highlight novel
      mechanisms of prostate homeostasis and insights into tumourigenesis.

PMID- 23145035
TI  - Mycorrhizal response to experimental pH and P manipulation in acidic hardwood
      forests.
AB  - Many temperate forests of the Northeastern United States and Europe have received
      significant anthropogenic acid and nitrogen (N) deposition over the last century.
      Although temperate hardwood forests are generally thought to be N-limited,
      anthropogenic deposition increases the possibility of phosphorus (P) limiting
      productivity in these forest ecosystems. Moreover, inorganic P availability is
      largely controlled by soil pH and biogeochemical theory suggests that forests
      with acidic soils (i.e., <pH 5) are particularly vulnerable to P limitation.
      Results from previous studies in these systems are mixed with evidence both for
      and against P limitation. We hypothesized that shifts in mycorrhizal colonization
      and community structure help temperate forest ecosystems overcome an underlying P
      limitation by accessing mineral and organic P sources that are otherwise
      unavailable for direct plant uptake. We examined arbuscular mycorrhizal (AM) and
      ectomycorrhizal (EcM) communities and soil microbial activity in an ecosystem
      level experiment where soil pH and P availability were manipulated in mixed
      deciduous forests across eastern Ohio, USA. One year after treatment initiation,
      AM root biomass was positively correlated with the most available P pool, resin
      P, while AM colonization was negatively correlated. In total, 15,876 EcM root
      tips were identified and assigned to 26 genera and 219 operational taxonomic
      units (97% similarity). Ectomycorrhizal richness and root tip abundance were
      negatively correlated with the moderately available P pools, while the relative
      percent of tips colonized by Ascomycetes was positively correlated with soil pH.
      Canonical correspondence analysis revealed regional, but not treatment,
      differences in AM communities, while EcM communities had both treatment and
      regional differences. Our findings highlight the complex interactions between
      mycorrhizae and the soil environment and further underscore the fact that
      mycorrhizal communities do not merely reflect the host plant community.

PMID- 23145036
TI  - Hypoxia-inducible factor activation protects the kidney from gentamicin-induced
      acute injury.
AB  - Gentamicin nephrotoxicity is one of the most common causes of acute kidney injury
      (AKI). Hypoxia-inducible factor (HIF) is effective in protecting the kidney from
      ischemic and toxic injury. Increased expression of HIF-1alpha mRNA has been
      reported in rats with gentamicin-induced renal injury. We hypothesizd that we
      could study the role of HIF in gentamicin-induced AKI by modulating HIF activity.
      In this study, we investigated whether HIF activation had protective effects on
      gentamicin-induced renal tubule cell injury. Gentamicin-induced AKI was
      established in male Sprague-Dawley rats. Cobalt was continuously infused into the
      rats to activate HIF. HK-2 cells were pre-treated with cobalt or
      dimethyloxalylglycine (DMOG) to activate HIF and were then exposed to gentamicin.
      Cobalt or DMOG significantly increased HIF-1alpha expression in rat kidneys and
      HK-2 cells. In HK-2 cells, HIF inhibited gentamicin-induced reactive oxygen
      species (ROS) formation. HIF also protected these cells from apoptosis by
      reducing caspase-3 activity and the amount of cleaved caspase-3, and -9 proteins.
      Increased expression of HIF-1alpha reduced the number of gentamicin-induced
      apoptotic cells in rat kidneys and HK-2 cells. HIF activation improved the
      creatinine clearance and proteinuria in gentamicin-induced AKI. HIF activation
      also ameliorated the extent of histologic injury and reduced macrophage
      infiltration into the tubulointerstitium. In gentamicin-induced AKI, the
      activation of HIF by cobalt or DMOG attenuated renal dysfunction, proteinuria,
      and structural damage through a reduction of oxidative stress, inflammation, and
      apoptosis in renal tubular epithelial cells.

PMID- 23145037
TI  - Sex-related effects of reproduction on biomarkers of oxidative damage in free
      living barn swallows (Hirundo rustica).
AB  - According to life-history theory, the allocation of limiting resources to one
      trait has negative consequences for other traits requiring the same resource,
      resulting in trade-offs among life-history traits, such as reproduction and
      survival. In vertebrates, oxidative stress is increasingly being considered among
      the physiological mechanisms forming the currency of life-history trade-offs. In
      this study of the barn swallow (Hirundo rustica), we focus on the oxidative costs
      of reproduction, especially egg laying, by investigating the effects of breeding
      stage (pre- vs. post-laying) and progression of the season on three biomarkers of
      oxidative damage (OD) to plasma proteins, namely the concentration of
      malondialdehyde (MDA)-protein adducts and of protein thiol groups (PSH), and the
      protein carbonyl (PCO) content. Moreover, we investigated whether males and
      females differed in plasma OD levels, because the inherent sex differences in
      reproductive roles and physiology may originate sex-specific patterns of OD
      during breeding. We found that MDA-protein adduct levels were higher in the pre
      laying than in the post-laying phase, that males had lower levels of MDA-modified
      proteins than females, and that the decline of MDA-protein adduct concentration
      between the pre- and the post-laying phase was more marked for females than
      males. In addition, MDA-protein adduct levels declined with sampling date, but
      only during the pre-laying phase. On the other hand, plasma PCO levels increased
      from the pre- to the post-laying phase in both sexes, and females had higher
      levels of PCO than males. PSH concentration was unaffected by breeding stage, sex
      or sampling date. On the whole, our findings indicate that biomarkers of protein
      oxidation closely track the short-term variation in breeding stage of both male
      and female barn swallows. Moreover, the higher protein OD levels observed among
      females compared to males suggest that egg laying entails oxidative costs, which
      might negatively affect female residual reproductive value.

PMID- 23145038
TI  - Titanium dioxide nanoparticles increase sensitivity in the next generation of the
      water flea Daphnia magna.
AB  - The nanoparticle industry is expected to become a trillion dollar business in the
      near future. Therefore, the unintentional introduction of nanoparticles into the
      environment is increasingly likely. However, currently applied risk-assessment
      practices require further adaptation to accommodate the intrinsic nature of
      engineered nanoparticles. Combining a chronic flow-through exposure system with
      subsequent acute toxicity tests for the standard test organism Daphnia magna, we
      found that juvenile offspring of adults that were previously exposed to titanium
      dioxide nanoparticles exhibit a significantly increased sensitivity to titanium
      dioxide nanoparticles compared with the offspring of unexposed adults, as
      displayed by lower 96 h-EC(50) values. This observation is particularly
      remarkable because adults exhibited no differences among treatments in terms of
      typically assessed endpoints, such as sensitivity, number of offspring, or energy
      reserves. Hence, the present study suggests that ecotoxicological research
      requires further development to include the assessment of the environmental risks
      of nanoparticles for the next and hence not directly exposed generation, which is
      currently not included in standard test protocols.

PMID- 23145039
TI  - MicroRNA-550a acts as a pro-metastatic gene and directly targets cytoplasmic
      polyadenylation element-binding protein 4 in hepatocellular carcinoma.
AB  - MicroRNAs (miRNAs) are a class of small, non-coding RNA molecules that are often
      found at chromosomal breakpoints and play a vital role in human cancer. Our
      previous study found that miR-550a, a frequently amplified miRNA on 7p14.3, was
      upregulated in hepatocellular carcinoma (HCC). However, the possible functions
      and molecular mechanisms of miR-550a in HCC remain unknown. In this study, gain
      of-function and loss-of-function assays revealed that miR-550a markedly promoted
      HCC cell migration and invasion. In addition, we discovered that cytoplasmic
      polyadenylation element binding protein 4 (CPEB4) was a potential target of miR
      550a in HCC. Further analyses showed that knockdown of CPEB4 expression
      significantly facilitated HCC cell migration and invasion, which phenocopied the
      effects of miR-550a on HCC cells. Moreover, a decrease in CPEB4 expression
      mediated miR-550a-induced liver cancer cell migration and invasion.
      Interestingly, CPEB4 is frequently downregulated in HCC, and its expression
      levels correlate with the overall survival of HCC patients. Together, these
      results suggested that this newly identified miR-550a-CPEB4 axis may be involved
      in HCC cell metastasis. Moreover, the expression levels of CPEB4 could be used to
      predict outcomes in HCC patients. Our findings provide novel potential targets
      for HCC therapy and prognosis.

PMID- 23145040
TI  - Differences in HCV viral decline between low and standard-dose pegylated
      interferon-alpha-2a with ribavirin in HIV/HCV genotype 3 patients.
AB  - BACKGROUND: The aim of the study was to analyze the different impact of standard
      and low-dose Peg-IFN-alpha2a/RBV therapies on HCV viral decline in HIV/HCV
      genotype 3 co-infected patients during the first weeks of treatment. METHODS:
      Plasma HCV viral decline was analyzed between baseline and weeks 1, 2 and 4 in
      two groups of treatment-naive HCV genotype 3 patients with HIV co-infection. The
      Standard Dose Group (SDG) included patients who received Peg-IFN at 180 ug/per
      week with a weight-adjusted dose of ribavirin; Low-Dose Group (LDG) patients
      received Peg-IFN at 135 ug/per week with 800 mg/day ribavirin. The effect of
      IL28B genotype on HCV viral decline was evaluated in both groups. HCV viral
      decline was analyzed using a multivariate linear regression model. RESULTS: One
      hundred and six patients were included: 48 patients in the SDG and 58 in the LDG.
      HCV viral decline for patients in the LDG was less than for those in the SDG
      (week 1:1.72+/-0.74 log(10) IU/mL versus 1.78+/-0.67 log(10) IU/mL, p = 0.827;
      week 2:2.3+/-0.89 log(10) IU/mL versus 3.01+/-1.02 log(10) IU/mL, p = 0.013; week
      4:3.52+/-1.2 log(10) IU/mL versus 4.09+/-1.1 log(10) IU/mL, p = 0.005). The
      linear regression model identified the Peg-IFN/RBV dose as an independent factor
      for HCV viral decline at week 4. CONCLUSIONS: Our results showed that HCV viral
      decline was less for patients in the low-dose group compared to those receiving
      the standard dose. Until a randomized clinical trial is conducted, clinicians
      should be cautious about using lower doses of Peg-IFN/RBV in HIV/HCV genotype 3
      co-infected patients.

PMID- 23145042
TI  - Systematic determination of replication activity type highlights interconnections
      between replication, chromatin structure and nuclear localization.
AB  - DNA replication is a highly regulated process, with each genomic locus
      replicating at a distinct time of replication (ToR). Advances in ToR measurement
      technology enabled several genome-wide profiling studies that revealed tight
      associations between ToR and general genomic features and a remarkable ToR
      conservation in mammals. Genome wide studies further showed that at the hundreds
      kb-to-megabase scale the genome can be divided into constant ToR regions (CTRs)
      in which the replication process propagates at a faster pace due to the
      activation of multiple origins and temporal transition regions (TTRs) in which
      the replication process propagates at a slower pace. We developed a computational
      tool that assigns a ToR to every measured locus and determines its replication
      activity type (CTR versus TTR). Our algorithm, ARTO (Analysis of Replication
      Timing and Organization), uses signal processing methods to fit a constant piece
      wise linear curve to the measured raw data. We tested our algorithm and provide
      performance and usability results. A Matlab implementation of ARTO is available
      at http://bioinfo.cs.technion.ac.il/people/zohar/ARTO/. Applying our algorithm to
      ToR data measured in multiple mouse and human samples allowed precise genome-wide
      ToR determination and replication activity type characterization. Analysis of the
      results highlighted the plasticity of the replication program. For example, we
      observed significant ToR differences in 10-25% of the genome when comparing
      different tissue types. Our analyses also provide evidence for activity type
      differences in up to 30% of the probes. Integration of the ToR data with multiple
      aspects of chromosome organization characteristics suggests that ToR plays a role
      in shaping the regional chromatin structure. Namely, repressive chromatin marks,
      are associated with late ToR both in TTRs and CTRs. Finally, characterization of
      the differences between TTRs and CTRs, with matching ToR, revealed that TTRs are
      associated with compact chromatin and are located significantly closer to the
      nuclear envelope. Supplementary material is available. Raw and processed data
      were deposited in Geo (GSE17236).

PMID- 23145041
TI  - DlgS97/SAP97, a neuronal isoform of discs large, regulates ethanol tolerance.
AB  - From a genetic screen for Drosophila melanogaster mutants with altered ethanol
      tolerance, we identified intolerant (intol), a novel allele of discs large 1
      (dlg1). Dlg1 encodes Discs Large 1, a MAGUK (Membrane Associated Guanylate
      Kinase) family member that is the highly conserved homolog of mammalian PSD-95
      and SAP97. The intol mutation disrupted specifically the expression of DlgS97, a
      SAP97 homolog, and one of two major protein isoforms encoded by dlg1 via
      alternative splicing. Expression of the major isoform, DlgA, a PSD-95 homolog,
      appeared unaffected. Ethanol tolerance in the intol mutant could be partially
      restored by transgenic expression of DlgS97, but not DlgA, in specific neurons of
      the fly's brain. Based on co-immunoprecipitation, DlgS97 forms a complex with N
      methyl-D-aspartate (NMDA) receptors, a known target of ethanol. Consistent with
      these observations, flies expressing reduced levels of the essential NMDA
      receptor subunit dNR1 also showed reduced ethanol tolerance, as did mutants in
      the gene calcium/calmodulin-dependent protein kinase (caki), encoding the fly
      homolog of mammalian CASK, a known binding partner of DlgS97. Lastly, mice in
      which SAP97, the mammalian homolog of DlgS97, was conditionally deleted in adults
      failed to develop rapid tolerance to ethanol's sedative/hypnotic effects. We
      propose that DlgS97/SAP97 plays an important and conserved role in the
      development of tolerance to ethanol via NMDA receptor-mediated synaptic
      plasticity.

PMID- 23145043
TI  - A phylogenomic approach to vertebrate phylogeny supports a turtle-archosaur
      affinity and a possible paraphyletic lissamphibia.
AB  - In resolving the vertebrate tree of life, two fundamental questions remain: 1)
      what is the phylogenetic position of turtles within amniotes, and 2) what are the
      relationships between the three major lissamphibian (extant amphibian) groups?
      These relationships have historically been difficult to resolve, with five
      different hypotheses proposed for turtle placement, and four proposed branching
      patterns within Lissamphibia. We compiled a large cDNA/EST dataset for
      vertebrates (75 genes for 129 taxa) to address these outstanding questions. Gene
      specific phylogenetic analyses revealed a great deal of variation in preferred
      topology, resulting in topologically ambiguous conclusions from the combined
      dataset. Due to consistent preferences for the same divergent topologies across
      genes, we suspected systematic phylogenetic error as a cause of some variation.
      Accordingly, we developed and tested a novel statistical method that identifies
      sites that have a high probability of containing biased signal for a specific
      phylogenetic relationship. After removing putatively biased sites, support
      emerged for a sister relationship between turtles and either crocodilians or
      archosaurs, as well as for a caecilian-salamander sister relationship within
      Lissamphibia, with Lissamphibia potentially paraphyletic.

PMID- 23145044
TI  - MetaSee: an interactive and extendable visualization toolbox for metagenomic
      sample analysis and comparison.
AB  - The NGS (next generation sequencing)-based metagenomic data analysis is becoming
      the mainstream for the study of microbial communities. Faced with a large amount
      of data in metagenomic research, effective data visualization is important for
      scientists to effectively explore, interpret and manipulate such rich
      information. The visualization of the metagenomic data, especially multi-sample
      data, is one of the most critical challenges. The different data sample sources,
      sequencing approaches and heterogeneous data formats make robust and seamless
      data visualization difficult. Moreover, researchers have different focuses on
      metagenomic studies: taxonomical or functional, sample-centric or genome-centric,
      single sample or multiple samples, etc. However, current efforts in metagenomic
      data visualization cannot fulfill all of these needs, and it is extremely hard to
      organize all of these visualization effects in a systematic manner. An
      extendable, interactive visualization tool would be the method of choice to
      fulfill all of these visualization needs. In this paper, we have present MetaSee,
      an extendable toolbox that facilitates the interactive visualization of
      metagenomic samples of interests. The main components of MetaSee include: (I) a
      core visualization engine that is composed of different views for comparison of
      multiple samples: Global view, Phylogenetic view, Sample view and Taxa view, as
      well as link-out for more in-depth analysis; (II) front-end user interface with
      real metagenomic models that connect to the above core visualization engine and
      (III) open-source portal for the development of plug-ins for MetaSee. This
      integrative visualization tool not only provides the visualization effects, but
      also enables researchers to perform in-depth analysis of the metagenomic samples
      of interests. Moreover, its open-source portal allows for the design of plug-ins
      for MetaSee, which would facilitate the development of any additional
      visualization effects.

PMID- 23145045
TI  - An aptamer-based biosensor for colorimetric detection of Escherichia coli
      O157:H7.
AB  - BACKGROUND: An aptamer based biosensor (aptasensor) was developed and evaluated
      for rapid colorimetric detection of Escherichia coli (E. coli) O157:H7.
      METHODOLOGY/PRINCIPAL FINDINGS: The aptasensor was assembled by modifying the
      truncated lipopolysaccharides (LPS)-binding aptamer on the surface of nanoscale
      polydiacetylene (PDA) vesicle using peptide bonding between the carboxyl group of
      the vesicle and the amine group of the aptamer. Molecular recognition between E.
      coli O157:H7 and aptamer at the interface of the vesicle lead to blue-red
      transition of PDA which was readily visible to the naked eyes and could be
      quantified by colorimetric responses (CR). Confocal laser scanning microscope
      (CLSM) and transmission electron microscopy (TEM) was used to confirm the
      specific interactions between the truncated aptamer and E. coli O157:H7. The
      aptasensor could detect cellular concentrations in a range of 10(4)~ 10(8) colony
      forming units (CFU)/ml within 2 hours and its specificity was 100% for detection
      of E. coli O157:H7. Compared with the standard culture method, the correspondent
      rate was 98.5% for the detection of E. coli O157:H7 on 203 clinical fecal
      specimens with our aptasensor. CONCLUSIONS: The new aptasensor represents a
      significant advancement in detection capabilities based on the combination of
      nucleic acid aptamer with PDA vesicle, and offers a specific and convenient
      screening method for the detection of pathogenic bacteria. This technic could
      also be applied in areas from clinical analysis to biological terrorism defense,
      especially in low-resource settings.

PMID- 23145046
TI  - Birds and viruses at a crossroad--surveillance of influenza A virus in Portuguese
      waterfowl.
AB  - During recent years, extensive amounts of data have become available regarding
      influenza A virus (IAV) in wild birds in northern Europe, while information from
      southern Europe is more limited. Here, we present an IAV surveillance study
      conducted in western Portugal 2008-2009, analyzing 1653 samples from six
      different species of waterfowl, with the majority of samples taken from Mallards
      (Anas platyrhynchos). Overall 4.4% of sampled birds were infected. The sampling
      results revealed a significant temporal variation in the IAV prevalence,
      including a pronounced peak among predominantly young birds in June, indicating
      that IAV circulate within breeding populations in the wetlands of western
      Portugal. The H10N7 and H9N2 subtypes were predominant among isolated viruses.
      Phylogenetic analyses of the hemagglutinin and neuraminidase sequences of H10N7,
      H9N2 and H11N3 virus showed that sequences from Portugal were closely related to
      viral sequences from Central Europe as well as to IAVs isolated in the southern
      parts of Africa, reflecting Portugal's position on the European-African bird
      migratory flyway. This study highlights the importance of Portugal as a migratory
      crossroad for IAV, connecting breeding stationary waterfowl with birds migrating
      between continents which enable transmission and spread of IAV.

PMID- 23145047
TI  - Variation in the mechanical unfolding pathway of p53DBD induced by interaction
      with p53 N-terminal region or DNA.
AB  - The tumor suppressor p53 plays a crucial role in the cell cycle checkpoints, DNA
      repair, and apoptosis. p53 consists of a natively unfolded N-terminal region
      (NTR), central DNA binding domain (DBD), C-terminal tetramerization domain, and
      regulatory region. In this paper, the interactions between the DBD and the NTR,
      and between the DBD and DNA were investigated by measuring changes in the
      mechanical unfolding trajectory of the DBD using atomic force microscopy (AFM)
      based single molecule force spectroscopy. In the absence of DNA, the DBD (94-293,
      200 amino acids (AA)) showed two different mechanical unfolding patterns. One
      indicated the existence of an unfolding intermediate consisting of approximately
      60 AA, and the other showed a 100 AA intermediate. The DBD with the NTR did not
      show such unfolding patterns, but heterogeneous unfolding force peaks were
      observed. Of the heterogeneous patterns, we observed a high frequency of force
      peaks indicating the unfolding of a domain consisting of 220 AA, which is
      apparently larger than that of a sole DBD. This observation implies that a part
      of NTR binds to the DBD, and the mechanical unfolding happens not solely on the
      DBD but also accompanying a part of NTR. When DNA is bound, the mechanical
      unfolding trajectory of p53NTR+DBD showed a different pattern from that without
      DNA. The pattern was similar to that of the DBD alone, but two consecutive
      unfolding force peaks corresponding to 60 and 100 AA sub-domains were observed.
      These results indicate that interactions with the NTR or DNA alter the mechanical
      stability of DBD and result in drastic changes in the mechanical unfolding
      trajectory of the DBD.

PMID- 23145048
TI  - A genetic and pharmacological analysis of isoprenoid pathway by LC-MS/MS in
      fission yeast.
AB  - Currently, statins are the only drugs acting on the mammalian isoprenoid pathway.
      The mammalian genes in this pathway are not easily amenable to genetic
      manipulation. Thus, it is difficult to study the effects of the inhibition of
      various enzymes on the intermediate and final products in the isoprenoid pathway.
      In fission yeast, antifungal compounds such as azoles and terbinafine are
      available as inhibitors of the pathway in addition to statins, and various
      isoprenoid pathway mutants are also available. Here in these mutants, treated
      with statins or antifungals, we quantified the final and intermediate products of
      the fission yeast isoprenoid pathway using liquid chromatography-mass
      spectrometry/mass spectrometry. In hmg1-1, a mutant of the gene encoding 3
      hydroxy-3-methylglutaryl coenzyme A reductase (HMGR), ergosterol (a final sterol
      product), and squalene (an intermediate pathway product), were decreased to
      approximately 80% and 10%, respectively, compared with that of wild-type cells.
      Consistently in wild-type cells, pravastatin, an HMGR inhibitor decreased
      ergosterol and squalene, and the effect was more pronounced on squalene. In hmg1
      1 mutant and in wild-type cells treated with pravastatin, the decrease in the
      levels of farnesyl pyrophosphate and geranylgeranyl pyrophosphate respectively
      was larger than that of ergosterol but was smaller than that of squalene. In
      Deltaerg6 or Deltasts1 cells, mutants of the genes involved in the last step of
      the pathway, ergosterol was not detected, and the changes of intermediate product
      levels were distinct from that of hmg1-1 mutant. Notably, in wild-type cells
      miconazole and terbinafine only slightly decreased ergosterol level. Altogether,
      these studies suggest that the pleiotropic phenotypes caused by the hmg1-1
      mutation and pravastatin might be due to decreased levels of isoprenoid
      pyrophosphates or other isoprenoid pathway intermediate products rather than due
      to a decreased ergosterol level.

PMID- 23145049
TI  - Low mercury concentration produces vasoconstriction, decreases nitric oxide
      bioavailability and increases oxidative stress in rat conductance artery.
AB  - Mercury is an environmental pollutant that reduces nitric oxide (NO)
      bioavailability and increases oxidative stress, having a close link with
      cardiovascular diseases, as carotid atherosclerosis, myocardial infarction,
      coronary heart disease and hypertension. One of the main sites affected by
      oxidative stress, which develops atherosclerosis, is the aorta. Under acute
      exposure to low mercury concentrations reactive oxygen species (ROS) production
      were only reported for resistance vessels but if low concentrations of mercury
      also affect conductance arteries it is still unclear. We investigated the acute
      effects of 6 nM HgCl(2) on endothelial function of aortic rings measuring the
      reactivity to phenylephrine in rings incubated, or not, with HgCl(2) for 45 min,
      the protein expression for cyclooxygenase 2 (COX-2) and the AT1 receptor. HgCl(2)
      increased Rmax and pD2 to phenylephrine without changing the vasorelaxation
      induced by acetylcholine and sodium nitroprusside. Endothelial damage abolished
      the increased reactivity to phenylephrine. The increase of Rmax and pD2 produced
      by L-NAME was smaller in the presence of HgCl(2). Enalapril, losartan,
      indomethacin, furegrelate, the selective COX-2 inhibitor NS 398, superoxide
      dismutase and the NADPH oxidase inhibitor apocynin reverted HgCl(2) effects on
      the reactivity to phenylephrine, COX-2 protein expression was increased, and AT1
      expression reduced. At low concentration, below the reference values, HgCl(2)
      increased vasoconstrictor activity by reducing NO bioavailability due to
      increased ROS production by NADPH oxidase activity. Results suggest that this is
      due to local release of angiotensin II and prostanoid vasoconstrictors. Results
      also suggest that acute low concentration mercury exposure, occurring time to
      time could induce vascular injury due to endothelial oxidative stress and
      contributing to increase peripheral resistance, being a high risk factor for
      public health.

PMID- 23145050
TI  - The Ca(2+) influence on calmodulin unfolding pathway: a steered molecular
      dynamics simulation study.
AB  - The force-induced unfolding of calmodulin (CaM) was investigated at atomistic
      details with steered molecular dynamics. The two isolated CaM domains as well as
      the full-length CaM were simulated in N-C-terminal pulling scheme, and the
      isolated N-lobe of CaM was studied specially in two other pulling schemes to test
      the effect of pulling direction and compare with relevant experiments. Both
      Ca(2+)-loaded CaM and Ca(2+)-free CaM were considered in order to define the
      Ca(2+) influence to the CaM unfolding. The results reveal that the Ca(2+)
      significantly affects the stability and unfolding behaviors of both the isolated
      CaM domains and the full-length CaM. In Ca(2+)-loaded CaM, N-terminal domain
      unfolds in priori to the C-terminal domain. But in Ca(2+)-free CaM, the unfolding
      order changes, and C-terminal domain unfolds first. The force-extension curves of
      CaM unfolding indicate that the major unfolding barrier comes from conquering the
      interaction of two EF-hand motifs in both N- and C- terminal domains. Our results
      provide the atomistic-level insights in the force-induced CaM unfolding and
      explain the observation in recent AFM experiments.

PMID- 23145051
TI  - Identification of proteins sensitive to thermal stress in human neuroblastoma and
      glioma cell lines.
AB  - Heat-shock is an acute insult to the mammalian proteome. The sudden elevation in
      temperature has far-reaching effects on protein metabolism, leads to a rapid
      inhibition of most protein synthesis, and the induction of protein chaperones.
      Using heat-shock in cells of neuronal (SH-SY5Y) and glial (CCF-STTG1) lineage, in
      conjunction with detergent extraction and sedimentation followed by LC-MS/MS
      proteomic approaches, we sought to identify human proteins that lose solubility
      upon heat-shock. The two cell lines showed largely overlapping profiles of
      proteins detected by LC-MS/MS. We identified 58 proteins in detergent insoluble
      fractions as losing solubility in after heat shock; 10 were common between the 2
      cell lines. A subset of the proteins identified by LC-MS/MS was validated by
      immunoblotting of similarly prepared fractions. Ultimately, we were able to
      definitively identify 3 proteins as putatively metastable neural proteins; FEN1,
      CDK1, and TDP-43. We also determined that after heat-shock these cells accumulate
      insoluble polyubiquitin chains largely linked via lysine 48 (K-48) residues.
      Collectively, this study identifies human neural proteins that lose solubility
      upon heat-shock. These proteins may represent components of the human proteome
      that are vulnerable to misfolding in settings of proteostasis stress.

PMID- 23145052
TI  - Corticospinal facilitation during observation of graspable objects: a
      transcranial magnetic stimulation study.
AB  - In 1979, Gibson first advanced the idea that the sight of graspable objects
      automatically activates in the observer the repertoire of actions necessary to
      interact with them, even in the absence of any intention to act ("affordance
      effect"). The neurophysiological substrate of this effect was later identified in
      a class of bimodal neurons, the so-called "canonical" neurons, located within
      monkey premotor cortex. In humans, even if different behavioral studies supported
      the existence of affordance effect, neurophysiological investigations exploring
      its neural substrates showed contradictory results. Here, by means of
      Transcranial Magnetic Stimulation (TMS), we explored the time-course of the
      "affordance effect" elicited by the observation of everyday-life graspable
      objects on motor cortex of resting observers. We recorded motor evoked potentials
      (MEP) from three intrinsic hand muscles (two "synergic" for grasping, OP and FDI
      and one "neutral", ADM). We found that objects' vision determined an increased
      excitability at 120 milliseconds after their presentation. Moreover, this
      modulation was proved to be specific to the cortical representations of synergic
      muscles. From an evolutionary perspective, this timing perfectly fits with a fast
      recruitment of the motor system aimed at rapidly and accurately choosing the
      appropriate motor plans in a competitive environment filled with different
      opportunities.

PMID- 23145053
TI  - The chicken ovalbumin upstream promoter-transcription factor II negatively
      regulates the transactivation of androgen receptor in prostate cancer cells.
AB  - Androgen receptor (AR) is involved in the development and progression of prostate
      cancers. However, the mechanisms by which this occurs remain incompletely
      understood. In previous reports, chicken ovalbumin upstream promoter
      transcription factor II (COUP-TF II) has been suggested to play a role in the
      development of cancers. In the present study, we explored a putative role of COUP
      TF II in prostate cancers by investigating its effect on cell proliferation and a
      cross-talk between COUP-TF II and AR. Overexpression of COUP-TF II results in the
      inhibition of androgen-dependent proliferation of prostate cancer cells. Further
      studies show that COUP-TF II functions as a corepressor of AR. It represses AR
      transactivation on target promoters containing the androgen response element
      (ARE) in a dose-dependent manner. In addition, COUP-TF II interacts physically
      with AR in vitro and in vivo. It binds to both the DNA binding domain (DBD) and
      the ligand-binding domain (LBD) of AR and disrupts the N/C terminal interaction
      of AR. Furthermore, COUP-TF II competes with coactivators such as ARA70, SRC-1,
      and GRIP1 to modulate AR transactivation as well as inhibiting the recruitment of
      AR to its ARE-containing target promoter. Taken together, our findings suggest
      that COUP-TF II is a novel corepressor of AR, and provide an insight into the
      role of COUP-TF II in prostate cancers.

PMID- 23145055
TI  - Testing the paradox of enrichment along a land use gradient in a multitrophic
      aboveground and belowground community.
AB  - In the light of ongoing land use changes, it is important to understand how
      multitrophic communities perform at different land use intensities. The paradox
      of enrichment predicts that fertilization leads to destabilization and extinction
      of predator-prey systems. We tested this prediction for a land use intensity
      gradient from natural to highly fertilized agricultural ecosystems. We included
      multiple aboveground and belowground trophic levels and land use-dependent
      searching efficiencies of insects. To overcome logistic constraints of field
      experiments, we used a successfully validated simulation model to investigate
      plant responses to removal of herbivores and their enemies. Consistent with our
      predictions, instability measured by herbivore-induced plant mortality increased
      with increasing land use intensity. Simultaneously, the balance between
      herbivores and natural enemies turned increasingly towards herbivore dominance
      and natural enemy failure. Under natural conditions, there were more frequently
      significant effects of belowground herbivores and their natural enemies on plant
      performance, whereas there were more aboveground effects in agroecosystems. This
      result was partly due to the "boom-bust" behavior of the shoot herbivore
      population. Plant responses to herbivore or natural enemy removal were much more
      abrupt than the imposed smooth land use intensity gradient. This may be due to
      the presence of multiple trophic levels aboveground and belowground. Our model
      suggests that destabilization and extinction are more likely to occur in
      agroecosystems than in natural communities, but the shape of the relationship is
      nonlinear under the influence of multiple trophic interactions.

PMID- 23145054
TI  - Supplementation of persimmon leaf ameliorates hyperglycemia, dyslipidemia and
      hepatic fat accumulation in type 2 diabetic mice.
AB  - Persimmon Leaf (PL), commonly consumed as herbal tea and traditional medicines,
      contains a variety of compounds that exert antioxidant, alpha-amylase and alpha
      glucosidase inhibitory activity. However, little is known about the in vivo
      effects and underlying mechanisms of PL on hyperglycemia, hyperlipidemia and
      hepatic steatosis in type 2 diabetes. Powered PL (5%, w/w) was supplemented with
      a normal diet to C57BL/KsJ-db/db mice for 5 weeks. PL decreased blood glucose,
      HOMA-IR, plasma triglyceride and total cholesterol levels, as well as liver
      weight, hepatic lipid droplets, triglycerides and cholesterol contents, while
      increasing plasma HDL-cholesterol and adiponectin levels. The anti-hyperglycemic
      effect was linked to decreased activity of gluconeogenic enzymes as well as
      increased glycogen content, glucokinase activity and its mRNA level in the liver.
      PL also led to a decrease in lipogenic transcriptional factor PPARgamma as well
      as gene expression and activity of enzymes involved in lipogenesis, with a
      simultaneous increase in fecal lipids, which are seemingly attributable to the
      improved hyperlipidemia and hepatic steatosis and decreased hepatic fatty acid
      oxidation. Furthermore, PL ameliorated plasma and hepatic oxidative stress.
      Supplementation with PL may be an effective dietary strategy to improve type 2
      diabetes accompanied by dyslipidemia and hepatic steatosis by partly modulating
      the activity or gene expression of enzymes related to antioxidant, glucose and
      lipid homeostasis.

PMID- 23145056
TI  - Structures of SHV-1 beta-lactamase with penem and penam sulfone inhibitors that
      form cyclic intermediates stabilized by carbonyl conjugation.
AB  - Bacterial beta-lactamase enzymes are in large part responsible for the decreased
      ability of beta-lactam antibiotics to combat infections. The inability to
      overcome beta-lactamase mediated resistance spurred the development of inhibitors
      with penems and penam sulfones being amongst the most potent and broad spectrum
      mechanism-based inactivators. These inhibitors form covalent, "suicide-type"
      inhibitory intermediates that are attached to the catalytic S70 residue. To
      further probe the details of the mechanism of beta-lactamase inhibition by these
      novel compounds, we determined the crystal structures of SHV-1 bound with penem
      1, and penam sulfones SA1-204 and SA3-53. Comparison with each other and with
      previously determined crystal structures of members of these classes of
      inhibitors suggests that the final conformation of the covalent adduct can vary
      greatly amongst the complex structures. In contrast, a common theme of carbonyl
      conjugation as a mechanism to avoid deacylation emerges despite that the penem
      and penam sulfone inhibitors form different types of intermediates. The detailed
      insights gained from this study could be used to further improve new mechanism
      based inhibitors of these common class A serine beta-lactamases.

PMID- 23145057
TI  - High yields of hydrogen production induced by meta-substituted dichlorophenols
      biodegradation from the green alga Scenedesmus obliquus.
AB  - Hydrogen is a highly promising energy source with important social and economic
      implications. The ability of green algae to produce photosynthetic hydrogen under
      anaerobic conditions has been known for years. However, until today the yield of
      production has been very low, limiting an industrial scale use. In the present
      paper, 73 years after the first report on H(2)-production from green algae, we
      present a combinational biological system where the biodegradation procedure of
      one meta-substituted dichlorophenol (m-dcp) is the key element for maintaining
      continuous and high rate H(2)-production (>100 times higher than previously
      reported) in chloroplasts and mitochondria of the green alga Scenedesmus
      obliquus. In particular, we report that reduced m-dcps (biodegradation
      intermediates) mimic endogenous electron and proton carriers in chloroplasts and
      mitochondria, inhibit Photosystem II (PSII) activity (and therefore O(2)
      production) and enhance Photosystem I (PSI) and hydrogenase activity. In
      addition, we show that there are some indications for hydrogen production from
      sources other than chloroplasts in Scenedesmus obliquus. The regulation of these
      multistage and highly evolved redox pathways leads to high yields of hydrogen
      production and paves the way for an efficient application to industrial scale
      use, utilizing simple energy sources and one meta-substituted dichlorophenol as
      regulating elements.

PMID- 23145058
TI  - A Sox2 BAC transgenic approach for targeting adult neural stem cells.
AB  - The transcription factor gene Sox2 is expressed in embryonic neural
      stem/progenitor cells and previous evidence suggests that it is also expressed in
      adult neural stem cells. To target Sox2-expressing neural stem/progenitor cells
      in a temporal manner, we generated a bacterial artificial chromosome (BAC)
      transgenic mouse line, in which an inducible form of Cre, CreERTM, is expressed
      under Sox2 regulatory elements. Inducible Cre activity in these mice was
      characterized using floxed reporters. During development, the Sox2-CreER
      transgenic mice show inducible Cre activity specifically in CNS stem/progenitor
      cells, making them a useful tool to regulate the expression of floxed genes
      temporally in embryonic neural stem/progenitor cells. In the adult, we examined
      the cell-specific expression of Sox2 and performed long-term lineage tracing.
      Four months after the transient induction of Cre activity, recombined GFAP+ stem
      like cells and DCX+ neuroblasts were still abundant in the neurogenic regions
      including the subventricular zone (SVZ), rostral migratory stream (RMS), and
      subgranular zone (SGZ) of the dentate gyrus. These results provide definitive in
      vivo evidence that Sox2 is expressed in neural stem cells (NSC) in both the SVZ
      and SGZ that are capable of self-renewal and long-term neurogenesis. Therefore,
      Sox2-CreER mice should be useful in targeting floxed genes in adult neural stem
      cells.

PMID- 23145059
TI  - Cohesion fatigue explains why pharmacological inhibition of the APC/C induces a
      spindle checkpoint-dependent mitotic arrest.
AB  - The Spindle Assembly Checkpoint (SAC) delays the onset of anaphase in response to
      unattached kinetochores by inhibiting the activity of the Anaphase-Promoting
      Complex/Cyclosome (APC/C), an E3 ubiquitin ligase. Once all the chromosomes have
      bioriented, SAC signalling is somehow silenced, which allows progression through
      mitosis. Recent studies suggest that the APC/C itself participates in SAC
      silencing by targeting an unknown factor for proteolytic degradation. Key
      evidence in favour of this model comes from the use of proTAME, a small molecule
      inhibitor of the APC/C. In cells, proTAME causes a mitotic arrest that is SAC
      dependent. Even though this observation comes at odds with the current view that
      the APC/C acts downstream of the SAC, it was nonetheless argued that these
      results revealed a role for APC/C activity in SAC silencing. However, we show
      here that the mitotic arrest induced by proTAME is due to the induction of
      cohesion fatigue, a phenotype that is caused by the loss of sister chromatid
      cohesion following a prolonged metaphase. Under these conditions, the SAC is re
      activated and APC/C inhibition is maintained independently of proTAME. Therefore,
      these results provide a simpler explanation for why the proTAME-induced mitotic
      arrest is also dependent on the SAC. While these observations question the notion
      that the APC/C is required for SAC silencing, we nevertheless show that APC/C
      activity does partially contribute to its own release from inhibitory complexes,
      and importantly, this does not depend on proteasome-mediated degradation.

PMID- 23145060
TI  - Imbalances between matrix metalloproteinases (MMPs) and tissue inhibitor of
      metalloproteinases (TIMPs) in maternal serum during preterm labor.
AB  - BACKGROUND: Matrix metalloproteinases (MMPs) are involved in remodeling of the
      extracellular matrix (ECM) during pregnancy and parturition. Aberrant ECM
      degradation by MMPs or an imbalance between MMPs and their tissue inhibitors
      (TIMPs) have been implicated in the pathogenesis of preterm labor, however few
      studies have investigated MMPs or TIMPs in maternal serum. Therefore, the purpose
      of this study was to determine serum concentrations of MMP-3, MMP-9 and all four
      TIMPs as well as MMP:TIMP ratios during term and preterm labor. METHODS: A case
      control study with 166 singleton pregnancies, divided into four groups: (1) women
      with preterm birth, delivering before 34 weeks (PTB); (2) gestational age (GA)
      matched controls, not in preterm labor; (3) women at term in labor and (4) at
      term not in labor. MMP and TIMP concentrations were measured using Luminex
      technology. RESULTS: MMP-9 and TIMP-4 concentrations were higher in women with
      PTB vs. GA matched controls (resp. p = 0.01 and p<0.001). An increase in MMP
      9:TIMP-1 and MMP-9:TIMP-2 ratio was observed in women with PTB compared to GA
      matched controls (resp. p = 0.02 and p<0.001) as well as compared to women at
      term in labor (resp. p = 0.006 and p<0.001). Multiple regression results with
      groups recoded as three key covariates showed significantly higher MMP-9
      concentrations, higher MMP-9:TIMP-1 and MMP-9:TIMP-2 ratios and lower TIMP-1 and 
      2 concentrations for preterm labor. Significantly higher MMP-9 and TIMP-4
      concentrations and MMP-9:TIMP-2 ratios were observed for labor. CONCLUSIONS:
      Serum MMP-9:TIMP-1 and MMP-9:TIMP-2 balances are tilting in favor of
      gelatinolysis during preterm labor. TIMP-1 and -2 concentrations were lower in
      preterm gestation, irrespective of labor, while TIMP-4 concentrations were raised
      in labor. These observations suggest that aberrant serum expression of MMP:TIMP
      ratios and TIMPs reflect pregnancy and labor status, providing a far less
      invasive method to determine enzymes essential in ECM remodeling during pregnancy
      and parturition.

PMID- 23145061
TI  - Cyanobacteria produce N-(2-aminoethyl)glycine, a backbone for peptide nucleic
      acids which may have been the first genetic molecules for life on Earth.
AB  - Prior to the evolution of DNA-based organisms on earth over 3.5 billion years ago
      it is hypothesized that RNA was the primary genetic molecule. Before RNA-based
      organisms arose, peptide nucleic acids may have been used to transmit genetic
      information by the earliest forms of life on earth. We discovered that
      cyanobacteria produce N-(2-aminoethyl)glycine (AEG), a backbone for peptide
      nucleic acids. We detected AEG in axenic strains of cyanobacteria with an average
      concentration of 1 ug/g. We also detected AEG in environmental samples of
      cyanobacteria as both a free or weakly bound molecule and a tightly bound form
      released by acid hydrolysis, at concentrations ranging from not detected to 34
      ug/g. The production of AEG by diverse taxa of cyanobacteria suggests that AEG
      may be a primitive feature which arose early in the evolution of life on earth.

PMID- 23145062
TI  - Human ALKBH4 interacts with proteins associated with transcription.
AB  - The Fe(II)- and 2-oxoglutarate (2OG)-dependent dioxygenase AlkB from E. coli is a
      demethylase which repairs alkyl lesions in DNA, as well as RNA, through a direct
      reversal mechanism. Humans possess nine AlkB homologs (ALKBH1-8 and FTO). ALKBH2
      and ALKBH3 display demethylase activities corresponding to that of AlkB, and both
      ALKBH8 and FTO are RNA modification enzymes. The biochemical functions of the
      rest of the homologs are still unknown. To increase our knowledge on the
      functions of ALKBH4 and ALKBH7 we have here performed yeast two-hybrid screens to
      identify interaction partners of the two proteins. While no high-confidence hits
      were detected in the case of ALKBH7, several proteins associated with chromatin
      and/or involved in transcription were found to interact with ALKBH4. For all
      interaction partners, the regions mediating binding to ALKBH4 comprised domains
      previously reported to be involved in interaction with DNA or chromatin.
      Furthermore, some of these partners showed nuclear co-localization with ALKBH4.
      However, the global gene expression pattern was only marginally altered upon
      ALKBH4 over-expression, and larger effects were observed in the case of ALKBH7.
      Although the molecular function of both proteins remains to be revealed, our
      findings suggest a role for ALKBH4 in regulation of gene expression or chromatin
      state.

PMID- 23145063
TI  - Relationship between the inflammatory molecular profile of breast carcinomas and
      distant metastasis development.
AB  - Inflammatory conditions may promote tumor progression and aggressiveness. In
      previous reports, we found a group of breast cancer tumors characterized by
      metalloprotease-11 (MMP-11) expression by intratumoral mononuclear inflammatory
      cells (MICs), which was associated with distant metastasis development. Thus, in
      the present study we evaluated the relationship between MMP-11 expression by
      MICs, distant metastasis development, and a wide panel of inflammatory factors in
      breast carcinoma. In an initial approach, we analyzed 65 factors associated with
      tumor progression and inflammation, in a tumor population classified in good or
      bad prognosis, based on MMP-11 expression by intratumoral MICs. The most
      differentially expressed factors were then analyzed in a wider tumor population
      classified according to MMP-11 expression by MICs and also according to
      metastasis development. These analyses were carried out by Real-time PCR. The
      results showed that of the 65 starting factors analyzed, those related with MMP
      11 expression by MICs were: IL-1, -5, -6, -8, -17, -18, MMP-1, TIMP-1, ADAM-8, 
      10, -15, -23, ADAMTS-1, -2, -15, Annexin A2, IFNbeta, Claudin-3, CCL-3, MyD88,
      IRAK-4 and NFkappaB. Of them, factors more differentially expressed between both
      groups of tumors were IL-1, IL-5, IL-6, IL-17, IFNbeta and NFkappaB. Thereafter,
      we confirmed in the wider tumor population, that there is a higher expression of
      those factors in tumors infiltrated by MMP-11 positive MICs. Altogether these
      results indicate that tumors developing worse prognosis and identified by MMP-11
      expression by intratumoral MICs, shows an up-regulation of inflammatory-related
      genes.

PMID- 23145064
TI  - Structural basis for group B streptococcus pilus 1 sortases C regulation and
      specificity.
AB  - Gram-positive bacteria assemble pili through class C sortase enzymes specialized
      in polymerizing pilin subunits into covalently linked, high-molecular-weight,
      elongated structures. Here we report the crystal structures of two class C
      sortases (SrtC1 and SrtC2) from Group B Streptococcus (GBS) Pilus Island 1. The
      structures show that both sortases are comprised of two domains: an 8-stranded
      beta-barrel catalytic core conserved among all sortase family members and a
      flexible N-terminal region made of two alpha-helices followed by a loop, known as
      the lid, which acts as a pseudo-substrate. In vitro experiments performed with
      recombinant SrtC enzymes lacking the N-terminal portion demonstrate that this
      region of the enzyme is dispensable for catalysis but may have key roles in
      substrate specificity and regulation. Moreover, in vitro FRET-based assays show
      that the LPXTG motif common to many sortase substrates is not the sole
      determinant of sortase C specificity during pilin protein recognition.

PMID- 23145065
TI  - Identification of small molecules with type I interferon inducing properties by
      high-throughput screening.
AB  - The continuous emergence of virus that are resistant to current anti-viral drugs,
      combined with the introduction of new viral pathogens for which no therapeutics
      are available, creates an urgent need for the development of novel broad spectrum
      antivirals. Type I interferon (IFN) can, by modulating the cellular expression
      profile, stimulate a non-specific antiviral state. The antiviral and adjuvant
      properties of IFN have been extensively demonstrated; however, its clinical
      application has been so far limited. We have developed a human cell-based assay
      that monitors IFN-beta production for use in a high throughput screen. Using this
      assay we screened 94,398 small molecules and identified 18 compounds with IFN
      inducing properties. Among these, 3 small molecules (C3, E51 and L56) showed
      activity not only in human but also in murine and canine derived cells. We
      further characterized C3 and showed that this molecule is capable of stimulating
      an anti-viral state in human-derived lung epithelial cells. Furthermore, the IFN
      induction by C3 is not diminished by the presence of influenza A virus NS1
      protein or hepatitis C virus NS3/4A protease, which make this molecule an
      interesting candidate for the development of a new type of broad-spectrum
      antiviral. In addition, the IFN-inducing properties of C3 also suggest its
      potential use as vaccine adjuvant.

PMID- 23145066
TI  - Association between smoking and latent tuberculosis in the U.S. population: an
      analysis of the National Health and Nutrition Examination Survey.
AB  - BACKGROUND: Evidence of an association between cigarette smoking and latent
      tuberculosis infection (LTBI) is based on studies in special populations and/or
      from high prevalence settings. We sought to evaluate the association between LTBI
      and smoking in a low prevalence TB setting using population-based data from the
      National Health and Nutrition Examination Survey (NHANES). METHODS: In 1999-2000,
      NHANES assessed LTBI (defined as a tuberculin skin test measurement >=10 mm) in
      participants, and those >=20 years of age were queried regarding their tobacco
      use and serum cotinine was measured. We evaluated the association of LTBI with
      self-reported smoking history and smoking intensity in multivariable logistic
      regression models that adjusted for known confounders (gender, age, birthplace,
      race/ethnicity, poverty, education, history of BCG vaccination, and history of
      household exposure to tuberculosis disease). RESULTS: Estimated LTBI prevalence
      was 5.3% among those >=20 years of age. The LTBI prevalence among never smokers,
      current smokers, and former smokers was 4.1%, 6.6%, and 6.2%, respectively. In a
      multivariable model, current smoking was associated with LTBI (OR 1.8; 95% CI,
      1.1-2.9). The association between smoking and LTBI was strongest for Mexican
      American and black individuals. In multivariate analysis stratified by
      race/ethnicity, cigarette packs per day among Mexican-American smokers and
      cotinine levels among black smokers, were significantly associated with LTBI.
      CONCLUSIONS: In the large, representative, population-based NHANES sample,
      smoking was independently associated with significantly increased risks of LTBI.
      In certain populations, a greater risk of LTBI corresponded with increased
      smoking exposure.

PMID- 23145067
TI  - Oncogenic kit triggers Shp2/Erk1/2 pathway to down-regulate the pro-apoptotic
      protein Bim and to promote apoptosis resistance in leukemic cells.
AB  - Oncogenic mutations leading to persistent kinase activities are implicated in
      various human malignancies. Thereby, signaling pathway-targeted therapies are
      powerful customized treatment to eradicate cancer cells. In murine and human
      leukemia cells harboring mutations in Kit, we previously showed that distinct and
      independent pathways controlled resistance to apoptosis or cell cycle. A
      treatment with PI3Kinase inhibitors to reduce cell proliferation combined with
      inhibitors of Erk1/2 activity to promote apoptosis had synergistic effects
      allowing eradication of leukemia cell growth. We reported here that Bim(EL), a
      pro-apoptotic member of the Bcl2 family proteins, is the target of Erk1/2
      signaling and that its down-regulation is responsible for the apoptosis
      resistance of murine and human leukemic cells. Downstream of Kit mutant, the
      tyrosine phosphatase Shp2 maintains Bim(EL) expression at a low level, through
      Erk/2 activation and proteosomal Bim(EL) degradation. This process is controlled
      by Shp2 independently of other signaling pathways activated downstream of
      oncogenic Kit, demonstrating that Shp2 is a key regulator of Bim expression in
      the context of an oncogenic signaling. The increase in Bim(EL) expression is
      associated to an increased apoptosis. Moreover, the depletion of Bim overcomes
      apoptosis associated with Erk1/2 inactivation in UO126-treated leukemic cells,
      thereby establishing the contribution of Bim to drug-induced apoptosis. These
      data provide a molecular rationale for using BH3 mimetics in combination with
      PI3K inhibitors to treat leukemia, especially in the case of an oncogenic
      signaling refractory to Tyrosine Kinase inhibitors.

PMID- 23145069
TI  - Identification and functional analysis of the erh1(+) gene encoding enhancer of
      rudimentary homolog from the fission yeast Schizosaccharomyces pombe.
AB  - The ERH gene encodes a highly conserved small nuclear protein with a unique amino
      acid sequence and three-dimensional structure but unknown function. The gene is
      present in animals, plants, and protists but to date has only been found in few
      fungi. Here we report that ERH homologs are also present in all four species from
      the genus Schizosaccharomyces, S. pombe, S. octosporus, S. cryophilus, and S.
      japonicus, which, however, are an exception in this respect among Ascomycota and
      Basidiomycota. The ERH protein sequence is moderately conserved within the genus
      (58% identity between S. pombe and S.japonicus), but the intron-rich genes have
      almost identical intron-exon organizations in all four species. In S. pombe,
      erh1(+) is expressed at a roughly constant level during vegetative growth and
      adaptation to unfavorable conditions such as nutrient limitation and hyperosmotic
      stress caused by sorbitol. Erh1p localizes preferentially to the nucleus with the
      exception of the nucleolus, but is also present in the cytoplasm. Cells lacking
      erh1(+) have an aberrant cell morphology and a comma-like shape when cultured to
      the stationary phase, and exhibit a delayed recovery from this phase followed by
      slower growth. Loss of erh1(+) in an auxotrophic background results in enhanced
      arrest in the G1 phase following nutritional stress, and also leads to
      hypersensitivity to agents inducing hyperosmotic stress (sorbitol), inhibiting
      DNA replication (hydroxyurea), and destabilizing the plasma membrane (SDS); this
      hypersensitivity can be abolished by expression of S. pombe erh1(+) and, to a
      lesser extent, S. japonicus erh1(+) or human ERH. Erh1p fails to interact with
      the human Ciz1 and PDIP46/SKAR proteins, known molecular partners of human ERH.
      Our data suggest that in Schizosaccharomyces sp. erh1(+) is non-essential for
      normal growth and Erh1p could play a role in response to adverse environmental
      conditions and in cell cycle regulation.

PMID- 23145068
TI  - The subthalamic microlesion story in Parkinson's disease: electrode insertion
      related motor improvement with relative cortico-subcortical hypoactivation in
      fMRI.
AB  - Electrode implantation into the subthalamic nucleus for deep brain stimulation in
      Parkinson's disease (PD) is associated with a temporary motor improvement
      occurring prior to neurostimulation. We studied this phenomenon by functional
      magnetic resonance imaging (fMRI) when considering the Unified Parkinson's
      Disease Rating Scale (UPDRS-III) and collateral oedema. Twelve patients with PD
      (age 55.9+/- (SD)6.8 years, PD duration 9-15 years) underwent bilateral electrode
      implantation into the subthalamic nucleus. The fMRI was carried out after an
      overnight withdrawal of levodopa (OFF condition): (i) before and (ii) within
      three days after surgery in absence of neurostimulation. The motor task involved
      visually triggered finger tapping. The OFF/UPDRS-III score dropped from 33.8+/
      8.7 before to 23.3+/-4.8 after the surgery (p<0.001), correlating with the
      postoperative oedema score (p<0.05). During the motor task, bilateral activation
      of the thalamus and basal ganglia, motor cortex and insula were preoperatively
      higher than after surgery (p<0.001). The results became more enhanced after
      compensation for the oedema and UPDRS-III scores. In addition, the rigidity and
      axial symptoms score correlated inversely with activation of the putamen and
      globus pallidus (p<0.0001). One month later, the OFF/UPDRS-III score had returned
      to the preoperative level (35.8+/-7.0, p = 0.4).In conclusion, motor improvement
      induced by insertion of an inactive electrode into the subthalamic nucleus caused
      an acute microlesion which was at least partially related to the collateral
      oedema and associated with extensive impact on the motor network. This was
      postoperatively manifested as lowered movement-related activation at the cortical
      and subcortical levels and differed from the known effects of neurostimulation or
      levodopa. The motor system finally adapted to the microlesion within one month as
      suggested by loss of motor improvement and good efficacy of deep brain
      stimulation.

PMID- 23145070
TI  - Thimerosal-induced apoptosis in mouse C2C12 myoblast cells occurs through
      suppression of the PI3K/Akt/survivin pathway.
AB  - BACKGROUND: Thimerosal, a mercury-containing preservative, is one of the most
      widely used preservatives and found in a variety of biological products. Concerns
      over its possible toxicity have reemerged recently due to its use in vaccines.
      Thimerosal has also been reported to be markedly cytotoxic to neural tissue.
      However, little is known regarding thimerosal-induced toxicity in muscle tissue.
      Therefore, we investigated the cytotoxic effect of thimerosal and its possible
      mechanisms on mouse C2C12 myoblast cells. METHODOLOGY/PRINCIPAL FINDINGS: The
      study showed that C2C12 myoblast cells underwent inhibition of proliferation and
      apoptosis after exposure to thimerosal (125-500 nM) for 24, 48 and 72 h.
      Thimerosal caused S phase arrest and induced apoptosis as assessed by flow
      cytometric analysis, Hoechst staining and immunoblotting. The data revealed that
      thimerosal could trigger the leakage of cytochrome c from mitochondria, followed
      by cleavage of caspase-9 and caspase-3, and that an inhibitor of caspase could
      suppress thimerosal-induced apoptosis. Thimerosal inhibited the phosphorylation
      of Akt(ser473) and survivin expression. Wortmannin, a PI3K inhibitor, inhibited
      Akt activity and decreased survivin expression, resulting in increased thimerosal
      induced apoptosis in C2C12 cells, while the activation of PI3K/Akt pathway by
      mIGF-I (50 ng/ml) increased the expression of survivin and attenuated apoptosis.
      Furthermore, the inhibition of survivin expression by siRNA enhanced thimerosal
      induced cell apoptosis, while overexpression of survivin prevented thimerosal
      induced apoptosis. Taken together, the data show that the PI3K/Akt/survivin
      pathway plays an important role in the thimerosal-induced apoptosis in C2C12
      cells. CONCLUSIONS/SIGNIFICANCE: Our results suggest that in C2C12 myoblast
      cells, thimerosal induces S phase arrest and finally causes apoptosis via
      inhibition of PI3K/Akt/survivin signaling followed by activation of the
      mitochondrial apoptotic pathway.

PMID- 23145071
TI  - The plasminogen activation system modulates differently adipogenesis and
      myogenesis of embryonic stem cells.
AB  - Regulation of the extracellular matrix (ECM) plays an important functional role
      either in physiological or pathological conditions. The plasminogen activation
      (PA) system, comprising the uPA and tPA proteases and their inhibitor PAI-1, is
      one of the main suppliers of extracellular proteolytic activity contributing to
      tissue remodeling. Although its function in development is well documented, its
      precise role in mouse embryonic stem cell (ESC) differentiation in vitro is
      unknown. We found that the PA system components are expressed at very low levels
      in undifferentiated ESCs and that upon differentiation uPA activity is detected
      mainly transiently, whereas tPA activity and PAI-1 protein are maximum in well
      differentiated cells. Adipocyte formation by ESCs is inhibited by amiloride
      treatment, a specific uPA inhibitor. Likewise, ESCs expressing ectopic PAI-1
      under the control of an inducible expression system display reduced adipogenic
      capacities after induction of the gene. Furthermore, the adipogenic
      differentiation capacities of PAI-1(-/-) induced pluripotent stem cells (iPSCs)
      are augmented as compared to wt iPSCs. Our results demonstrate that the control
      of ESC adipogenesis by the PA system correspond to different successive steps
      from undifferentiated to well differentiated ESCs. Similarly, skeletal myogenesis
      is decreased by uPA inhibition or PAI-1 overexpression during the terminal step
      of differentiation. However, interfering with uPA during days 0 to 3 of the
      differentiation process augments ESC myotube formation. Neither neurogenesis,
      cardiomyogenesis, endothelial cell nor smooth muscle formation are affected by
      amiloride or PAI-1 induction. Our results show that the PA system is capable to
      specifically modulate adipogenesis and skeletal myogenesis of ESCs by successive
      different molecular mechanisms.

PMID- 23145072
TI  - Protective effects of fluoxetine on decompression sickness in mice.
AB  - Massive bubble formation after diving can lead to decompression sickness (DCS)
      that can result in central nervous system disorders or even death. Bubbles alter
      the vascular endothelium and activate blood cells and inflammatory pathways,
      leading to a systemic pathophysiological process that promotes ischemic damage.
      Fluoxetine, a well-known antidepressant, is recognized as having anti
      inflammatory properties at the systemic level, as well as in the setting of
      cerebral ischemia. We report a beneficial clinical effect associated with
      fluoxetine in experimental DCS. 91 mice were subjected to a simulated dive at 90
      msw for 45 min before rapid decompression. The experimental group received 50
      mg/kg of fluoxetine 18 hours before hyperbaric exposure (n = 46) while controls
      were not treated (n = 45). Clinical assessment took place over a period of 30 min
      after surfacing. At the end, blood samples were collected for blood cells counts
      and cytokine IL-6 detection. There were significantly fewer manifestations of DCS
      in the fluoxetine group than in the controls (43.5% versus 75.5%, respectively; p
      = 0.004). Survivors showed a better and significant neurological recovery with
      fluoxetine. Platelets and red cells were significantly decreased after
      decompression in controls but not in the treated mice. Fluoxetine reduced
      circulating IL-6, a relevant marker of systemic inflammation in DCS. We concluded
      that fluoxetine decreased the incidence of DCS and improved motor recovery, by
      limiting inflammation processes.

PMID- 23145073
TI  - Interaction between soluble and membrane-embedded potassium channel peptides
      monitored by Fourier transform infrared spectroscopy.
AB  - Recent studies have explored the utility of Fourier transform infrared
      spectroscopy (FTIR) in dynamic monitoring of soluble protein-protein
      interactions. Here, we investigated the applicability of FTIR to detect
      interaction between synthetic soluble and phospholipid-embedded peptides
      corresponding to, respectively, a voltage-gated potassium (Kv) channel
      inactivation domain (ID) and S4-S6 of the Shaker Kv channel (KV1; including the
      S4-S5 linker "pre-inactivation" ID binding site). KV1 was predominantly alpha
      helical at 30 degrees C when incorporated into dimyristoyl-l-alpha
      phosphatidylcholine (DMPC) bilayers. Cooling to induce a shift in DMPC from
      liquid crystalline to gel phase reversibly decreased KV1 helicity, and was
      previously shown to partially extrude a synthetic S4 peptide. While no
      interaction was detected in liquid crystalline DMPC, upon cooling to induce the
      DMPC gel phase a reversible amide I peak (1633 cm(-1)) consistent with novel
      hydrogen bond formation was detected. This spectral shift was not observed for
      KV1 in the absence of ID (or vice versa), nor when the non-inactivating mutant
      V7E ID was applied to KV1 under similar conditions. Alteration of salt or redox
      conditions affected KV1-ID hydrogen bonding in a manner suggesting electrostatic
      KV1-ID interaction favored by a hairpin conformation for the ID and requiring
      extrusion of one or more KV1 domains from DMPC, consistent with ID binding to S4
      S5. These findings support the utility of FTIR in detecting reversible
      interactions between soluble and membrane-embedded proteins, with lipid state
      sensitivity of the conformation of the latter facilitating control of the
      interaction.

PMID- 23145074
TI  - Odour-mediated orientation of beetles is influenced by age, sex and morph.
AB  - The behaviour of insects is dictated by a combination of factors and may vary
      considerably between individuals, but small insects are often considered en masse
      and thus these differences can be overlooked. For example, the cowpea bruchid
      Callosobruchus maculatus F. exists naturally in two adult forms: the active
      (flight) form for dispersal, and the inactive (flightless), more fecund but
      shorter-lived form. Given that these morphs show dissimilar biology, it is
      possible that they differ in odour-mediated orientation and yet studies of this
      species frequently neglect to distinguish morph type, or are carried out only on
      the inactive morph. Along with sex and age of individual, adult morph could be an
      important variable determining the biology of this and similar species, informing
      studies on evolution, ecology and pest management. We used an olfactometer with
      motion-tracking to investigate whether the olfactory behaviour and orientation of
      C. maculatus towards infested and uninfested cowpeas and a plant-derived
      repellent compound, methyl salicylate, differed between morphs or sexes. We found
      significant differences between the behaviour of male and female beetles and
      beetles of different ages, as well as interactive effects of sex, morph and age,
      in response to both host and repellent odours. This study demonstrates that
      behavioural experiments on insects should control for sex and age, while also
      considering differences between adult morphs where present in insect species.
      This finding has broad implications for fundamental entomological research,
      particularly when exploring the relationships between physiology, behaviour and
      evolutionary biology, and the application of crop protection strategies.

PMID- 23145075
TI  - Diffusion tensor metrics as biomarkers in Alzheimer's disease.
AB  - BACKGROUND: Although diffusion tensor imaging has been a major research focus for
      Alzheimer's disease in recent years, it remains unclear whether it has sufficient
      stability to have biomarker potential. To date, frequently inconsistent results
      have been reported, though lack of standardisation in acquisition and analysis
      make such discrepancies difficult to interpret. There is also, at present, little
      knowledge of how the biometric properties of diffusion tensor imaging might
      evolve in the course of Alzheimer's disease. METHODS: The biomarker question was
      addressed in this study by adopting a standardised protocol both for the whole
      brain (tract-based spatial statistics), and for a region of interest: the midline
      corpus callosum. In order to study the evolution of tensor changes, cross
      sectional data from very mild (N = 21) and mild (N = 22) Alzheimer's disease
      patients were examined as well as a longitudinal cohort (N = 16) that had been
      rescanned at 12 months. FINDINGS AND SIGNIFICANCE: The results revealed that
      increased axial and mean diffusivity are the first abnormalities to occur and
      that the first region to develop such significant differences was mesial
      parietal/splenial white matter; these metrics, however, remained relatively
      static with advancing disease indicating they are suitable as 'state-specific'
      markers. In contrast, increased radial diffusivity, and therefore decreased
      fractional anisotropy-though less detectable early-became increasingly abnormal
      with disease progression, and, in the splenium of the corpus callosum, correlated
      significantly with dementia severity; these metrics therefore appear 'stage
      specific' and would be ideal for monitoring disease progression. In addition, the
      cross-sectional and longitudinal analyses showed that the progressive
      abnormalities in radial diffusivity and fractional anisotropy always occurred in
      areas that had first shown an increase in axial and mean diffusivity. Given that
      the former two metrics correlate with dementia severity, but the latter two did
      not, it would appear that increased axial diffusivity represents an upstream
      event that precedes neuronal loss.

PMID- 23145076
TI  - Modulation of pluripotency in the porcine embryo and iPS cells.
AB  - The establishment of the pluripotent ICM during early mammalian development is
      characterized by the differential expression of the transcription factors NANOG
      and GATA4/6, indicative of the epiblast and hypoblast, respectively. Differences
      in the mechanisms regulating the segregation of these lineages have been reported
      in many species, however little is known about this process in the porcine
      embryo. The aim of this study was to investigate the signalling pathways
      participating in the formation of the porcine ICM, and to establish whether their
      modulation can be used to increase the developmental potential of pluripotent
      cells. We show that blocking MEK signalling enhances the proportion of NANOG
      expressing cells in the ICM, but does not prevent the segregation of GATA-4
      cells. Interestingly, inhibition of FGF signalling does not alter the segregation
      of NANOG and GATA-4 cells, but affects the number of ICM cells. This indicates
      that FGF signalling participates in the formation of the founders of the ICM.
      Inhibition of MEK signalling combined with GSK3beta inhibition and LIF
      supplementation was used to modulate pluripotency in porcine iPS (piPS) cells. We
      demonstrate that under these stringent culture conditions piPS cells acquire
      features of naive pluripotency, characterized by the expression of STELLA and
      REX1, and increased in vitro germline differentiation capacity. We propose that
      small molecule inhibitors can be used to increase the homogeneity of induced
      pluripotent stem cell cultures. These improved culture conditions will pave the
      way for the generation of germline competent stem cells in this species.

PMID- 23145077
TI  - Global identification of prokaryotic glycoproteins based on an Escherichia coli
      proteome microarray.
AB  - Glycosylation is one of the most abundant protein posttranslational
      modifications. Protein glycosylation plays important roles not only in eukaryotes
      but also in prokaryotes. To further understand the roles of protein glycosylation
      in prokaryotes, we developed a lectin binding assay to screen glycoproteins on an
      Escherichia coli proteome microarray containing 4,256 affinity-purified E.coli
      proteins. Twenty-three E.coli proteins that bound Wheat-Germ Agglutinin (WGA)
      were identified. PANTHER protein classification analysis showed that these
      glycoprotein candidates were highly enriched in metabolic process and catalytic
      activity classes. One sub-network centered on deoxyribonuclease I (sbcB) was
      identified. Bioinformatics analysis suggests that prokaryotic protein
      glycosylation may play roles in nucleotide and nucleic acid metabolism. Fifteen
      of the 23 glycoprotein candidates were validated by lectin (WGA) staining,
      thereby increasing the number of validated E. coli glycoproteins from 3 to 18. By
      cataloguing glycoproteins in E.coli, our study greatly extends our understanding
      of protein glycosylation in prokaryotes.

PMID- 23145078
TI  - Lichen specific thallus mass and secondary compounds change across a
      retrogressive fire-driven chronosequence.
AB  - In the long-term absence of major disturbances ecosystems enter a state of
      retrogression, which involves declining soil fertility and consequently a
      reduction in decomposition rates. Recent studies have looked at how plant traits
      such as specific leaf mass and amounts of secondary compounds respond to
      declining soil fertility during retrogression, but there are no comparable
      studies for lichen traits despite increasing recognition of the role that lichens
      can play in ecosystem processes. We studied a group of 30 forested islands in
      northern Sweden differing greatly in fire history, and collectively representing
      a retrogressive chronosequence, spanning 5000 years. We used this system to
      explore how specific thallus mass (STM) and carbon based secondary compounds
      (CBSCs) change in three common epiphytic lichen species (Hypogymnia phsyodes,
      Melanohalea olivacea and Parmelia sulcata) as soil fertility declines during this
      retrogression. We found that STMs of lichens increased sharply during
      retrogression, and for all species soil N to P ratio (which increased during
      retrogression) was a strong predictor of STM. When expressed per unit area,
      medullary CBSCs in all species and cortical CBSCs in P. sulcata increased during
      retrogression. Meanwhile, when expressed per unit mass, only cortical CBSCs in H.
      physodes responded to retrogression, and in the opposite direction. Given that
      lichen functional traits are likely to be important in driving ecological
      processes that drive nutrient and carbon cycling in the way that plant functional
      traits are, the changes that they undergo during retrogression could potentially
      be significant for the functioning of the ecosystem.

PMID- 23145079
TI  - Timeliness of clinic attendance is a good predictor of virological response and
      resistance to antiretroviral drugs in HIV-infected patients.
AB  - BACKGROUND: Ensuring long-term adherence to therapy is essential for the success
      of HIV treatment. As access to viral load monitoring and genotyping is poor in
      resource-limited settings, a simple tool to monitor adherence is needed. We
      assessed the relationship between an indicator based on timeliness of clinic
      attendance and virological response and HIV drug resistance. METHODS: Data from 7
      virological cross-sectional studies were pooled. An adherence indicator was
      calculated as the number of appointments attended with delay divided by the
      number of months between antiretroviral treatment (ART) initiation and date of
      virological testing and multiplying this by 100. Delays of 1 or more to 5 or more
      days were considered in turn. Multivariate random-intercept logistic regression
      was fitted to examine the effect on outcomes, separately for adults and children.
      RESULTS: A total of 3580 adults and 253 children were included. Adults were
      followed for a median of 26.0 months (IQR 12.8-45.0) and attended a median of 24
      visits (IQR 13-34). The 1-day delay adherence indicator was strongly associated
      with viral load suppression (OR 0.96, 95% CI 0.95-0.97 per unit increase),
      virological failure (OR 1.05, 95% CI 1.03-1.06) and HIV drug resistance (OR 1.03,
      95% CI 1.01-1.05) after adjusting for initial age and CD4 count, previous ART
      experience, type of regimen and Tuberculosis diagnosis at start of therapy.
      Similar results were observed in children. CONCLUSION: An adherence indicator
      based on timeliness of clinic attendance predicts strongly both virological
      response and drug resistance, and could help to timely identify non-adherent
      patients in settings where viral load monitoring is not available.

PMID- 23145080
TI  - Initiation of early osteoblast differentiation events through the direct
      transcriptional regulation of Msx2 by FOXC1.
AB  - Hierarchal transcriptional regulatory networks function to control the correct
      spatiotemporal patterning of the mammalian skeletal system. One such factor, the
      forkhead box transcription factor FOXC1 is necessary for the correct formation of
      the axial and craniofacial skeleton. Previous studies have demonstrated that the
      frontal and parietal bones of the skull fail to develop in mice deficient for
      Foxc1. Furthermore expression of the Msx2 homeobox gene, an essential regulator
      of calvarial bone development is absent in the skull mesenchymal progenitors of
      Foxc1 mutant mice. Thus we sought to determine whether Msx2 was a direct target
      of FOXC1 transcriptional regulation. Here, we demonstrate that elevated
      expression of FOXC1 can increase endogenous Msx2 mRNA levels. Chromatin
      immunoprecipitation experiments reveal that FOXC1 occupies a conserved element in
      the MSX2 promoter. Using a luciferase reporter assay, we demonstrate that FOXC1
      can stimulate the activity of the both human and mouse MSX2 promoters. We also
      report that reducing FOXC1 levels by RNA interference leads to a decrease in MSX2
      expression. Finally, we demonstrate that heterologous expression of Foxc1 in
      C2C12 cells results in elevated alkaline phosphatase activity and increased
      expression of Runx2 and Msx2. These data indicate that Foxc1 expression leads to
      a similar enhanced osteogenic differentiation phenotype as observed with Msx2
      overexpression. Together these findings suggest that a Foxc1->Msx2 regulatory
      network functions in the initial stages of osteoblast differentiation.

PMID- 23145081
TI  - Frequent gain and loss of introns in fungal cytochrome b genes.
AB  - In this study, all available cytochrome b (Cyt b) genes from the GOBASE database
      were compiled and the evolutionary dynamics of the Cyt b gene introns was
      assessed. Cyt b gene introns were frequently present in the fungal kingdom and
      some lower plants, but generally absent or rare in Chromista, Protozoa, and
      Animalia. Fungal Cyt b introns were found at 35 positions in Cyt b genes and the
      number of introns varied at individual positions from a single representative to
      32 different introns at position 131, showing a wide and patchy distribution.
      Many homologous introns were present at the same position in distantly related
      species but absent in closely related species, suggesting that introns of the Cyt
      b genes were frequently lost. On the other hand, highly similar intron sequences
      were observed in some distantly related species rather than in closely related
      species, suggesting that these introns were gained independently, likely through
      lateral transfers. The intron loss-and-gain events could be mediated by
      transpositions that might have occurred between nuclear and mitochondria.
      Southern hybridization analysis confirmed that some introns contained repetitive
      sequences and might be transposable elements. An intron gain in Botryotinia
      fuckeliana prevented the development of QoI fungicide resistance, suggesting that
      intron loss-and-gain events were not necessarily beneficial to their host
      organisms.

PMID- 23145082
TI  - A neuronal network model for simulating the effects of repetitive transcranial
      magnetic stimulation on local field potential power spectra.
AB  - Repetitive transcranial magnetic stimulation (rTMS) holds promise as a non
      invasive therapy for the treatment of neurological disorders such as depression,
      schizophrenia, tinnitus, and epilepsy. Complex interdependencies between stimulus
      duration, frequency and intensity obscure the exact effects of rTMS stimulation
      on neural activity in the cortex, making evaluation of and comparison between
      rTMS studies difficult. To explain the influence of rTMS on neural activity (e.g.
      in the motor cortex), we use a neuronal network model. The results demonstrate
      that the model adequately explains experimentally observed short term effects of
      rTMS on the band power in common frequency bands used in electroencephalography
      (EEG). We show that the equivalent local field potential (eLFP) band power
      depends on stimulation intensity rather than on stimulation frequency.
      Additionally, our model resolves contradictions in experiments.

PMID- 23145083
TI  - Association of arterial stiffness and electrocardiography-determined left
      ventricular hypertrophy with left ventricular diastolic dysfunction.
AB  - OBJECTIVES: Increased arterial stiffness is associated with left ventricular
      diastolic dysfunction (LVDD), but this association may be influenced by left
      ventricular (LV) performance. Left ventricular hypertrophy (LVH) is not only a
      significant determinant of LV performance, but is also correlated with LVDD. This
      study is designed to compare LV diastolic function among patients divided by
      brachial-ankle pulse wave velocity (baPWV) and electrocardiography (ECG)
      determined LVH and to assess whether increased baPWV and ECG-determined LVH are
      independently associated with LVDD. METHODS: This cross-sectional study enrolled
      270 patients and classified them into four groups according to the median value
      of baPWV and with/without ECG-determined LVH. The baPWV was measured using an ABI
      form device. ECG-determined LVH was defined by Sokolow-Lyon criterion. LVDD was
      defined as impaired relaxation, pseudonormal, and restrictive mitral inflow
      patterns. Groups 1, 2, 3, and 4 were patients with lower baPWV and without ECG
      determined LVH, lower baPWV but with ECG-determined LVH, higher baPWV but without
      ECG-determined LVH, and higher baPWV and with ECG-determined LVH respectively.
      RESULTS: Early diastolic mitral velocity (Ea) was gradually decreased from group
      1 to group 4 (p?0.027). Patients in group 4 had the highest prevalence of LVDD
      (all p<0.001). After multivariate analysis, both baPWV and ECG-determined LVH
      were independent determinants of Ea (beta = -0.02, P<0.001; beta = -1.77, P<0.001
      respectively) and LVDD (odds ratio = 1.02, P = 0.011 and odds ratio = 3.53, P =
      0.013 respectively). CONCLUSION: Our study showed the group with higher baPWV and
      ECG-determined LVH had the lowest Ea and highest prevalence of LVDD. In addition,
      both baPWV and ECG-determined LVH were independently associated with Ea and LVDD.
      Hence, assessment of arterial stiffness by baPWV and LVH by ECG may be useful in
      identifying the high risk group of LVDD.

PMID- 23145084
TI  - Effects of PPARgamma and RBP4 gene variants on metabolic syndrome in HIV-infected
      patients with anti-retroviral therapy.
AB  - BACKGROUND: PPARgamma and RBP4 are known to regulate lipid and glucose metabolism
      and insulin resistance. The influences of PPARgamma (C1431T and Pro12Ala) and
      RBP4 (-803GA) polymorphisms on metabolic syndrome in HIV-infected patients
      receiving anti-retroviral therapy were examined in this study. MATERIALS AND
      METHODS: A cross-sectional study of HIV-1 infected adults with antiretroviral
      therapy for more than one year in the National Cheng Kung University Hospital was
      conducted. The gene polymorphisms were determined by quantitative PCR. RESULTS:
      Ninety-one patients were included in the study. Eighty-two (90.1%) patients were
      males with a mean age of 44.4 years. For the C1431T polymorphism in PPARgamma,
      while patients with the T allele (48.4%) had trends toward lower rate of
      hypertriglyceridemia, the borderline significance together with insignificant
      power did not support the protective effect of the T allele against development
      of hypertriglyceridemia. For the Pro12Ala polymorphism in PPARgamma, although
      patients with the Pro/Ala genotype (8.8%) had a higher level of serum LDL (138.0
      vs. 111.5 mg/dl, P = 0.04) and trends toward higher rates of hypercholesterolemia
      and serum LDL>110 mg/dl, these variables were found to be independent of the
      Pro/Ala genotype in the multivariate analysis. For the -803GA polymorphism in
      RBP4, patients with the A allele (23.1%) more often had insulin resistance
      (HOMA>3.8; 33.3 vs. 8.7%, P = 0.01) and more often received anti-hypoglycemic
      drugs (14.3 vs. 1.4%, P = 0.04). The detrimental effect of the A allele in RBP4 
      803GA polymorphism on development of insulin resistance was supported by the
      multivariate analysis adjusting for covariates. CONCLUSION: The impacts of
      PPARgamma C1431T and Pro12Ala polymorphisms on metabolism in HIV-infected
      patients are not significant. RBP4 -803GA polymorphism has increased risk of
      insulin resistance in HIV-infected patients with anti-retroviral therapy.

PMID- 23145085
TI  - A novel multiplex real-time PCR assay for the concurrent detection of hepatitis
      A, B and C viruses in patients with acute hepatitis.
AB  - A novel multiplex real-time PCR assay for concurrent detection of hepatitis
      viruses was evaluated for its clinical performance in screening patients with
      acute hepatitis. A total of 648 serum samples were collected from patients with
      acute symptoms of hepatitis. Concurrent detection of nucleic acids of HAV, HBV
      and HCV was performed using the MagicplexTM HepaTrio Real-time Detection test.
      Serum nucleic acid levels of HBV and HCV were also quantified by the Cobas(r)
      AmpliPrep/Cobas(r) TaqMan(r) (CAP/CTM) HBV and HCV tests. Patients' medical
      records were also reviewed. Concordance rates between the results from the
      HepaTrio and the CAP/CTM tests for the detection of HBV and HCV were 94.9% (k =
      0.88) and 99.2% (k = 0.98), respectively. The cycle threshold values with the
      HepaTrio test were also correlated well with the levels of HBV DNA (r = -0.9230)
      and HCV RNA (r = -0.8458). The sensitivity and specificity of the HepaTrio test
      were 93.8% and 98.2%, respectively, for detecting HBV infection, and 99.1% and
      100.0%, respectively, for HCV infection. For the HepaTrio test, 21 (3.2%) cases
      were positive for both HBV and HCV. Among the positive cases, 6 (0.9%) were true
      coinfections. This test also detected 18 (2.8%) HAV positives. The HepaTrio test
      demonstrated good clinical performance and produced results that agreed well with
      those of the CAP/CTM assays, especially for the detection of HCV. This assay was
      also able to detect HAV RNA from anti-HAV IgM-positive individuals. Therefore,
      this new multiplex PCR assay could be useful for the concurrent detection of the
      three hepatitis viruses.

PMID- 23145086
TI  - Characterization of Arabidopsis FPS isozymes and FPS gene expression analysis
      provide insight into the biosynthesis of isoprenoid precursors in seeds.
AB  - Arabidopsis thaliana contains two genes encoding farnesyl diphosphate (FPP)
      synthase (FPS), the prenyl diphoshate synthase that catalyzes the synthesis of
      FPP from isopentenyl diphosphate (IPP) and dimethylallyl diphosphate (DMAPP). In
      this study, we provide evidence that the two Arabidopsis short FPS isozymes FPS1S
      and FPS2 localize to the cytosol. Both enzymes were expressed in E. coli,
      purified and biochemically characterized. Despite FPS1S and FPS2 share more than
      90% amino acid sequence identity, FPS2 was found to be more efficient as a
      catalyst, more sensitive to the inhibitory effect of NaCl, and more resistant to
      thermal inactivation than FPS1S. Homology modelling for FPS1S and FPS2 and
      analysis of the amino acid differences between the two enzymes revealed an
      increase in surface polarity and a greater capacity to form surface salt bridges
      of FPS2 compared to FPS1S. These factors most likely account for the enhanced
      thermostability of FPS2. Expression analysis of FPS::GUS genes in seeds showed
      that FPS1 and FPS2 display complementary patterns of expression particularly at
      late stages of seed development, which suggests that Arabidopsis seeds have two
      spatially segregated sources of FPP. Functional complementation studies of the
      Arabidopsis fps2 knockout mutant seed phenotypes demonstrated that under normal
      conditions FPS1S and FPS2 are functionally interchangeable. A putative role for
      FPS2 in maintaining seed germination capacity under adverse environmental
      conditions is discussed.

PMID- 23145087
TI  - HIV-prevalence in tuberculosis patients in Germany, 2002-2009: an estimation
      based on HIV and tuberculosis surveillance data.
AB  - Tuberculosis (TB) and HIV comorbidity is a major challenge in TB prevention and
      control but difficult to assess in Germany as in other countries, where data
      confidentiality precludes notifying the HIV status of TB patients. We aimed to
      estimate the HIV-prevalence in TB patients in Germany, 2002-2009, and to
      characterize the HIV/TB patients demographically. Data from the long-term
      observational open multicentre cohort ClinSurv HIV were used to identify incident
      TB in HIV-positive individuals. We assessed the cohort's coverage for the
      nationwide HIV-positive population by contrasting ClinSurv HIV patients under
      antiretroviral therapy (ART) with national HIV patient numbers derived from ART
      prescriptions (data by Insight Health; available for 2006-2009). The HIV
      prevalence in TB patients was calculated as the number of HIV/TB cases projected
      for Germany over all culture-positive TB notifications. From 2002 to 2009, 298 of
      15,531 HIV-positive patients enrolled in the ClinSurv HIV cohort were diagnosed
      with TB. A 21% cohort coverage was determined. The annual estimates of the HIV
      prevalence in TB patients were on average 4.5% and ranged from 3.5% (95%CI 2.3
      5.1%) in 2007 to 6.6% (95%CI 5.0-8.5%) in 2005. The most recent estimate for 2009
      was 4.0% (95%CI 2.6-5.9%). The 298 HIV/TB patients were characterized by a male
      to-female ratio of 2.1, by a median age of 38 years at TB diagnosis, and by 59%
      of the patients having a foreign origin, mainly from Subsahara Africa. We
      provide, to our knowledge, the first estimate of the HIV-prevalence in TB
      patients for Germany by joint evaluation of anonymous HIV and TB surveillance
      data sources. The identified level of HIV in TB patients approximates available
      surveillance data from neighbouring countries and indicates a non-negligible
      HIV/TB burden in Germany. Our estimation approach is valuable for epidemiological
      monitoring of HIV/TB within the current legal frameworks.

PMID- 23145088
TI  - Risk of dementia in patients with insomnia and long-term use of hypnotics: a
      population-based retrospective cohort study.
AB  - BACKGROUND: Hypnotics have been reported to be associated with dementia. However,
      the relationship between insomnia, hypnotics and dementia is still controversial.
      We sought to examine the risk of dementia in patients with long-term insomnia and
      the contribution of hypnotics. METHODS: Data was collected from Taiwan's
      Longitudinal Health Insurance Database. The study cohort comprised all patients
      aged 50 years or older with a first diagnosis of insomnia from 2002 to 2007. The
      comparison cohort consisted of randomly selected patients matched by age and
      gender. Each patient was individually tracked for 3 years from their insomnia
      index date to identify whether the patient had a first diagnosis of dementia. Cox
      regression was used to estimate hazard ratios (HRs) and 95% confidence intervals
      (CIs). RESULTS: We identified 5693 subjects with long-term insomnia and 28,465
      individuals without. After adjusting for hypertension, diabetes mellitus,
      hyperlipidemia, and stroke, those with long-term insomnia had significantly
      higher risks of dementia (HR, 2.34; 95% CI, 1.92-2.85). Patients with long-term
      insomnia and aged 50 to 65 years had a higher increased risk of dementia (HR,
      5.22; 95% CI, 2.62-10.41) than those older than 65 years (HR, 2.33; 95% CI, 1.90
      2.88). The use of hypnotics with a longer half-life and at a higher prescribed
      dose predicted a greater increased risk of dementia. CONCLUSIONS: Patients with
      long-term use of hypnotics have more than a 2-fold increased risk of dementia,
      especially those aged 50 to 65 years. In addition, the dosage and half-lives of
      the hypnotics used should be considered, because greater exposure to these
      medications leads to a higher risk of developing dementia.

PMID- 23145089
TI  - Changes in defense of an alien plant Ambrosia artemisiifolia before and after the
      invasion of a native specialist enemy Ophraella communa.
AB  - The evolution of increased competitive ability hypothesis (EICA) predicts that
      when alien plants are free from their natural enemies they evolve lower
      allocation to defense in order to achieve a higher growth rate. If this
      hypothesis is true, the converse implication would be that the defense against
      herbivory could be restored if a natural enemy also becomes present in the
      introduced range. We tested this scenario in the case of Ambrosia artemisiifolia
      (common ragweed) - a species that invaded Japan from North America. We collected
      seeds from five North American populations, three populations in enemy free areas
      of Japan and four populations in Japan where the specialist herbivore Ophraella
      communa naturalized recently. Using plants grown in a common garden in Japan, we
      compared performance of O. communa with a bioassay experiment. Consistent with
      the EICA hypothesis, invasive Japanese populations of A. artemisiifolia exhibited
      a weakened defense against the specialist herbivores and higher growth rate than
      native populations. Conversely, in locations where the herbivore O. communa
      appeared during the past decade, populations of A. artemisiifolia exhibited
      stronger defensive capabilities. These results strengthen the case for EICA and
      suggest that defense levels of alien populations can be recuperated rapidly after
      the native specialist becomes present in the introduced range. Our study implies
      that the plant defense is evolutionary labile depending on plant-herbivore
      interactions.

PMID- 23145090
TI  - The population decline of Gyps vultures in India and Nepal has slowed since
      veterinary use of diclofenac was banned.
AB  - Populations of oriental white-backed vulture (Gyps bengalensis), long-billed
      vulture (Gyps indicus) and slender-billed vulture (Gyps tenuirostris) crashed
      during the mid-1990s throughout the Indian subcontinent. Surveys in India,
      initially conducted in 1991-1993 and repeated in 2000, 2002, 2003 and 2007,
      revealed that the population of Gyps bengalensis had fallen by 2007 to 0.1% of
      its numbers in the early 1990s, with the population of Gyps indicus and G.
      tenuirostris combined having fallen to 3.2% of its earlier level. A survey of G.
      bengalensis in western Nepal indicated that the size of the population in 2009
      was 25% of that in 2002. In this paper, repeat surveys conducted in 2011 were
      analysed to estimate recent population trends. Populations of all three species
      of vulture remained at a low level, but the decline had slowed and may even have
      reversed for G. bengalensis, both in India and Nepal. However, estimates of the
      most recent population trends are imprecise, so it is possible that declines may
      be continuing, though at a significantly slower rate. The degree to which the
      decline of G. bengalensis in India has slowed is consistent with the expected
      effects on population trend of a measured change in the level of contamination of
      ungulate carcasses with the drug diclofenac, which is toxic to vultures,
      following a ban on its veterinary use in 2006. The most recent available
      information indicates that the elimination of diclofenac from the vultures' food
      supply is incomplete, so further efforts are required to fully implement the ban.

PMID- 23145092
TI  - The Lon protease is essential for full virulence in Pseudomonas aeruginosa.
AB  - Pseudomonas aeruginosa PAO1 lon mutants are supersusceptible to ciprofloxacin,
      and exhibit a defect in cell division and in virulence-related properties, such
      as swarming, twitching and biofilm formation, despite the fact that the Lon
      protease is not a traditional regulator. Here we set out to investigate the
      influence of a lon mutation in a series of infection models. It was demonstrated
      that the lon mutant had a defect in cytotoxicity towards epithelial cells, was
      less virulent in an amoeba model as well as a mouse acute lung infection model,
      and impacted on in vivo survival in a rat model of chronic infection. Using qRT
      PCR it was demonstrated that the lon mutation led to a down-regulation of Type
      III secretion genes. The Lon protease also influenced motility and biofilm
      formation in a mucin-rich environment. Thus alterations in several virulence
      related processes in vitro in a lon mutant were reflected by defective virulence
      in vivo.

PMID- 23145091
TI  - Alcohol reward is increased after Roux-en-Y gastric bypass in dietary obese rats
      with differential effects following ghrelin antagonism.
AB  - Roux-en-Y gastric bypass (RYGB) is one of the most successful treatments for
      severe obesity and associated comorbidities. One potential adverse outcome,
      however, is increased risk for alcohol use. As such, we tested whether RYGB
      alters motivation to self-administer alcohol in outbred dietary obese rats, and
      investigated the involvement of the ghrelin system as a potential underlying
      mechanism. High fat (60%kcal from fat) diet-induced obese, non-diabetic male
      Sprague Dawley rats underwent RYGB (n = 9) or sham operation (Sham, n = 9) and
      were tested 4 months after surgery on a progressive ratio-10 (PR10) schedule of
      reinforcement operant task for 2, 4, and 8% ethanol. In addition, the effects of
      the ghrelin-1a-receptor antagonist D-[Lys3]-GHRP-6 (50, 100 nmol/kg, IP) were
      tested on PR10 responding for 4% ethanol. Compared to Sham, RYGB rats made
      significantly more active spout responses to earn reward, more consummatory licks
      on the ethanol spout, and achieved higher breakpoints. Pretreatment with a single
      peripheral injection of D-[Lys3]-GHRP-6 at either dose was ineffective in
      altering appetitive or consummatory responses to 4% ethanol in the Sham group. In
      contrast, RYGB rats demonstrated reduced operant performance to earn alcohol
      reward on the test day and reduced consummatory responses for two subsequent days
      following the drug. Sensitivity to threshold doses of D-[LYS3]-GHRP-6 suggests
      that an augmented ghrelin system may contribute to increased alcohol reward in
      RYGB. Further research is warranted to confirm applicability of these findings to
      humans and to explore ghrelin-receptor targets for treatment of alcohol-related
      disorders in RYGB patients.

PMID- 23145093
TI  - Ceasing intrathecal therapy in chronic non-cancer pain: an invitation to shift
      from biomedical focus to active management.
AB  - OBJECTIVE: To report long term experience (1997-2009) of intrathecal (IT) therapy
      for chronic non-cancer pain in the context of our team's increasing emphasis on
      active management. DESIGN: Descriptive case series. SETTING: Australian tertiary
      multidisciplinary pain center, Hunter Integrated Pain Service (HIPS).
      INTERVENTION: This case series reports the changing use of IT implanted drug
      delivery systems (IDDSs) for chronic non-cancer pain over 13 years. Initially IT
      therapy was used selectively following multidisciplinary assessment and double
      blind IT trial. Typical therapy combined opioid with clonidine. Multidimensional
      management was offered. Treatment strategy changed in 2003 due to HIPS experience
      of limited therapeutic gains and equivocal support for IT therapy in the
      literature. Subsequently IT therapy was no longer initiated for non-cancer pain
      and those on established regimes were encouraged to shift to oral/transdermal
      opioids with greater emphasis on active management. Patient education and
      consultation were key elements. Where IT cessation was elective gradual dose
      reduction commenced as an outpatient. In elective and urgent cases ketamine
      infusion and oral clonidine were used during hospital admissions to cover the
      switch to oral/transdermal opioids. Over the study period transition occurred to
      a broader management framework in which IT therapy for chronic non-cancer pain
      was no longer supported by HIPS. RESULTS: 25 patients were managed using IDDSs; 8
      implanted by HIPS and 17 by other teams. Dose escalation and adverse effects were
      common. 24 of 25 patients ceased IT therapy; 7 (29%) with urgent IDDS related
      complications, 16 (67%) electively and 1 due to an unrelated death. The remaining
      patient returned to her original team to continue IT therapy. One post
      explantation patient transferred to another team to recommence IT therapy. The
      remainder were successfully maintained on oral/transdermal opioids combined with
      active management.

PMID- 23145094
TI  - Risk factors of pneumothorax after endobronchial ultrasound-guided transbronchial
      biopsy for peripheral lung lesions.
AB  - BACKGROUND: The risk of endobronchial ultrasound-guided transbronchial biopsy
      related pneumothorax is a major concern and warrants further studies. The aim of
      our study was to estimate the risk of pneumothorax after this procedure and
      identify its risk factors. METHODS: From 2007 to 2011, 399 patients who underwent
      endobronchial ultrasound-guided transbronchial biopsy for peripheral lung lesions
      were included in this study. The variables analyzed included patient factors,
      lesion factors and procedure factors. Multivariate logistic regression analysis
      was used to identify independent risk factors for pneumothorax. RESULTS: The
      incidence of pneumothorax was 3.3% (13/399). Chest tube placement was required
      for 31% (4/13) of pneumothoraces. Independent risk factors for pneumothorax
      included pulmonary emphysema (OR, 55.09; 95% CI, 9.37-324.03; p<0.001) and probe
      position adjacent to the lesion (OR, 17.01; 95% CI, 2.85-101.64; p = 0.002). The
      number of biopsy specimens, age, sex, history of prior lung surgery and lesion
      size, location and character did not influence the risk of pneumothorax in our
      analyses. CONCLUSIONS: The risk of pneumothorax after endobronchial ultrasound
      guided transbronchial biopsy is low. To further reduce the risk of pneumothorax,
      every effort should be made to advance the endobronchial ultrasound probe into
      the bronchus where it is imaged within the target lesion before embarking on
      transbronchial biopsy.

PMID- 23145095
TI  - Measuring user similarity using electric circuit analysis: application to
      collaborative filtering.
AB  - We propose a new technique of measuring user similarity in collaborative
      filtering using electric circuit analysis. Electric circuit analysis is used to
      measure the potential differences between nodes on an electric circuit. In this
      paper, by applying this method to transaction networks comprising users and
      items, i.e., user-item matrix, and by using the full information about the
      relationship structure of users in the perspective of item adoption, we overcome
      the limitations of one-to-one similarity calculation approach, such as the
      Pearson correlation, Tanimoto coefficient, and Hamming distance, in collaborative
      filtering. We found that electric circuit analysis can be successfully
      incorporated into recommender systems and has the potential to significantly
      enhance predictability, especially when combined with user-based collaborative
      filtering. We also propose four types of hybrid algorithms that combine the
      Pearson correlation method and electric circuit analysis. One of the algorithms
      exceeds the performance of the traditional collaborative filtering by 37.5% at
      most. This work opens new opportunities for interdisciplinary research between
      physics and computer science and the development of new recommendation systems.

PMID- 23145096
TI  - Immunogenetic variation and differential pathogen exposure in free-ranging
      cheetahs across Namibian farmlands.
AB  - BACKGROUND: Genes under selection provide ecologically important information
      useful for conservation issues. Major histocompatibility complex (MHC) class I
      and II genes are essential for the immune defence against pathogens from
      intracellular (e.g. viruses) and extracellular (e.g. helminths) origins,
      respectively. Serosurvey studies in Namibian cheetahs (Acinonyx juabuts) revealed
      higher exposure to viral pathogens in individuals from north-central than east
      central regions. Here we examined whether the observed differences in exposure to
      viruses influence the patterns of genetic variation and differentiation at MHC
      loci in 88 free-ranging Namibian cheetahs. METHODOLOGY/PRINCIPAL FINDINGS:
      Genetic variation at MHC I and II loci was assessed through single-stranded
      conformation polymorphism (SSCP) analysis and sequencing. While the overall
      allelic diversity did not differ, we observed a high genetic differentiation at
      MHC class I loci between cheetahs from north-central and east-central Namibia. No
      such differentiation in MHC class II and neutral markers were found.
      CONCLUSIONS/SIGNIFICANCE: Our results suggest that MHC class I variation mirrors
      the variation in selection pressure imposed by viruses in free-ranging cheetahs
      across Namibian farmland. This is of high significance for future management and
      conservation programs of this species.

PMID- 23145097
TI  - Electrophysiological differences in the processing of affect misattribution.
AB  - The affect misattribution procedure (AMP) was proposed as a technique to measure
      an implicit attitude to a prime image [1]. In the AMP, neutral symbols (e.g., a
      Chinese pictograph, called the target) are presented, following an emotional
      stimulus (known as the prime). Participants often misattribute the positive or
      negative affect of the priming images to the targets in spite of receiving an
      instruction to ignore the primes. The AMP effect has been investigated using
      behavioral measures; however, it is difficult to identify when the AMP effect
      occurs in emotional processing-whether the effect may occur in the earlier
      attention allocation stage or in the later evaluation stage. In this study, we
      examined the neural correlates of affect misattribution, using event-related
      potential (ERP) dividing the participants into two groups based on their tendency
      toward affect misattribution. The ERP results showed that the amplitude of P2 was
      larger for the prime at the parietal location in participants showing a low
      tendency to misattribution than for those showing a high tendency, while the
      effect of judging neutral targets amiss according to the primes was reflected in
      the late processing of targets (LPP). In addition, the topographic pattern
      analysis revealed that EPN-like component to targets was correlated with the
      difference of AMP tendency as well as P2 to primes and LPP to targets. Taken
      together, the mechanism of the affective misattribution was closely related to
      the attention allocation processing. Our findings provide neural evidence that
      evaluations of neutral targets are misattributed to emotional primes.

PMID- 23145098
TI  - Meta-analysis of cytochrome P-450 2C9 polymorphism and colorectal cancer risk.
AB  - BACKGROUND: CYP2C9 encodes a member of the cytochrome P450 superfamily of enzymes
      which play a central role in activating and detoxifying many carcinogens and
      endogenous compounds thought to be involved in the development of colorectal
      cancer (CRC). In the past decade, the relationship between CYP2C9 common
      polymorphisms (R144C and I359L) and CRC has been reported in various ethnic
      groups; however, these studies have yielded contradictory results. To investigate
      this inconsistency, we performed this meta-analysis. METHODS: Databases including
      Pubmed, EMBASE, Web of Science and China National Knowledge Infrastructure (CNKI)
      were searched to find relevant studies. Odds ratios (ORs) with 95% confidence
      intervals (CIs) were used to assess the strength of association. RESULTS: A total
      of 13 articles involving 9,463 cases and 11,416 controls were included. Overall,
      the summary odds ratio of CRC was 0.98 (95% CI: 0.89-1.06) and 0.99 (95% CI: 0.87
      1.14) for CYP2C9 144C and 359L alleles, respectively. No significant results were
      observed using dominant or recessive genetic model for these polymorphisms. In
      the stratified analyses according to ethnicity and sex, no evidence of any gene
      disease association was obtained. CONCLUSIONS: This meta-analysis suggests that
      the CYP2C9 may not be associated with colorectal cancer development.

PMID- 23145099
TI  - Probing mixed-genotype infections II: high multiplicity in natural infections of
      the trypanosomatid, Crithidia bombi, in its host, Bombus spp.
AB  - Mixed-genotype infections have major consequences for many essential elements of
      host-parasite interactions. With genetic exchange between co-infecting parasite
      genotypes increased diversity among parasite offspring and the emergence of novel
      genotypes from infected hosts is possible. We here investigated mixed- genotype
      infections using the host, Bombus spp. and its trypanosome parasite Crithidia
      bombi as our study case. The natural infections of C. bombi were genotyped with a
      novel method for a representative sample of workers and spring queens in
      Switzerland. We found that around 60% of all infected hosts showed mixed-genotype
      infections with an average of 2.47+/-0.22 (S.E.) and 3.65+/-1.02 genotypes per
      worker or queen, respectively. Queens, however, harboured up to 29 different
      genotypes. Based on the genotypes of co-infecting strains, these could be
      putatively assigned to either 'primary' and 'derived' genotypes - the latter
      resulting from genetic exchange among the primary genotypes. High genetic
      relatedness among co-infecting derived but not primary genotypes supported this
      scenario. Co-infection in queens seems to be a major driver for the diversity of
      genotypes circulating in host populations.

PMID- 23145100
TI  - Understanding the impacts of land-use policies on a threatened species: is there
      a future for the Bornean orang-utan?
AB  - The geographic distribution of Bornean orang-utans and its overlap with existing
      land-use categories (protected areas, logging and plantation concessions) is a
      necessary foundation to prioritize conservation planning. Based on an extensive
      orang-utan survey dataset and a number of environmental variables, we modelled an
      orang-utan distribution map. The modelled orang-utan distribution map covers
      155,106 km(2) (21% of Borneo's landmass) and reveals four distinct distribution
      areas. The most important environmental predictors are annual rainfall and land
      cover. The overlap of the orang-utan distribution with land-use categories
      reveals that only 22% of the distribution lies in protected areas, but that 29%
      lies in natural forest concessions. A further 19% and 6% occurs in largely
      undeveloped oil palm and tree plantation concessions, respectively. The remaining
      24% of the orang-utan distribution range occurs outside of protected areas and
      outside of concessions. An estimated 49% of the orang-utan distribution will be
      lost if all forest outside of protected areas and logging concessions is lost. To
      avoid this potential decline plantation development in orang-utan habitats must
      be halted because it infringes on national laws of species protection. Further
      growth of the plantation sector should be achieved through increasing yields in
      existing plantations and expansion of new plantations into areas that have
      already been deforested. To reach this goal a large scale island-wide land-use
      masterplan is needed that clarifies which possible land uses and managements are
      allowed in the landscape and provides new standardized strategic conservation
      policies. Such a process should make much better use of non-market values of
      ecosystem services of forests such as water provision, flood control, carbon
      sequestration, and sources of livelihood for rural communities. Presently land
      use planning is more driven by vested interests and direct and immediate economic
      gains, rather than by approaches that take into consideration social equity and
      environmental sustainability.

PMID- 23145101
TI  - mRNA-Seq of single prostate cancer circulating tumor cells reveals recapitulation
      of gene expression and pathways found in prostate cancer.
AB  - Circulating tumor cells (CTC) mediate metastatic spread of many solid tumors and
      enumeration of CTCs is currently used as a prognostic indicator of survival in
      metastatic prostate cancer patients. Some evidence suggests that it is possible
      to derive additional information about tumors from expression analysis of CTCs,
      but the technical difficulty of isolating and analyzing individual CTCs has
      limited progress in this area. To assess the ability of a new generation of
      MagSweeper to isolate intact CTCs for downstream analysis, we performed mRNA-Seq
      on single CTCs isolated from the blood of patients with metastatic prostate
      cancer and on single prostate cancer cell line LNCaP cells spiked into the blood
      of healthy donors. We found that the MagSweeper effectively isolated CTCs with a
      capture efficiency that matched the CellSearch platform. However, unlike
      CellSearch, the MagSweeper facilitates isolation of individual live CTCs without
      contaminating leukocytes. Importantly, mRNA-Seq analysis showed that the
      MagSweeper isolation process did not have a discernible impact on the
      transcriptional profile of single LNCaPs isolated from spiked human blood,
      suggesting that any perturbations caused by the MagSweeper process on the
      transcriptional signature of isolated cells are modest. Although the RNA from
      patient CTCs showed signs of significant degradation, consistent with reports of
      short half-lives and apoptosis amongst CTCs, transcriptional signatures of
      prostate tissue and of cancer were readily detectable with single CTC mRNA-Seq.
      These results demonstrate that the MagSweeper provides access to intact CTCs and
      that these CTCs can potentially supply clinically relevant information.

PMID- 23145102
TI  - The stability of complement-mediated bactericidal activity in human serum against
      Salmonella.
AB  - The complement cascade includes heat-labile proteins and care is required when
      handling serum in order to preserve its functional integrity. We have previously
      used a whole human serum bactericidal assay to show that antibody and an intact
      complement system are required in blood for killing of invasive isolates of
      Salmonella. The aim of the present study was to evaluate the conditions under
      which human serum can be stored and manipulated while maintaining complement
      integrity. Serum bactericidal activity against Salmonella was maintained for a
      minimum of 35 days when stored at 4 degrees C, eight days at 22 degrees C and 54
      hours at 37 degrees C. Up to three freeze-thaw cycles had no effect on the
      persistence of bactericidal activity and hemolytic complement assays confirmed no
      effect on complement function. Delay in the separation of serum for up to four
      days from clotted blood stored at 22 degrees C did not affect bactericidal
      activity. Dilution of serum resulted in an increased rate of loss of bactericidal
      activity and so serum should be stored undiluted. These findings indicate that
      the current guidelines concerning manipulation and storage of human serum to
      preserve complement integrity and function leave a large margin for safety with
      regards to bactericidal activity against Salmonella. The study provides a scheme
      for determining the requirements for serum handling in relation to functional
      activity of complement in other systems.

PMID- 23145103
TI  - Induced tauopathy in a novel 3D-culture model mediates neurodegenerative
      processes: a real-time study on biochips.
AB  - Tauopathies including Alzheimer's disease represent one of the major health
      problems of aging population worldwide. Therefore, a better understanding of tau
      dependent pathologies and consequently, tau-related intervention strategies is
      highly demanded. In recent years, several tau-focused therapies have been
      proposed with the aim to stop disease progression. However, to develop efficient
      active pharmaceutical ingredients for the broad treatment of Alzheimer's disease
      patients, further improvements are necessary for understanding the detailed
      neurodegenerative processes as well as the mechanism and side effects of
      potential active pharmaceutical ingredients (API) in the neuronal system. In this
      context, there is a lack of suitable complex in vitro cell culture models
      recapitulating major aspects of taupathological degenerative processes in
      sufficient time and reproducible manner.Herewith, we describe a novel 3D SH-SY5Y
      cell-based, tauopathy model that shows advanced characteristics of matured
      neurons in comparison to monolayer cultures without the need of artificial
      differentiation promoting agents. Moreover, the recombinant expression of a novel
      highly pathologic fourfold mutated human tau variant lead to a fast and
      emphasized degeneration of neuritic processes. The neurodegenerative effects
      could be analyzed in real time and with high sensitivity using our unique
      microcavity array-based impedance spectroscopy measurement system. We were able
      to quantify a time- and concentration-dependent relative impedance decrease when
      Alzheimer's disease-like tau pathology was induced in the neuronal 3D cell
      culture model. In combination with the collected optical information, the
      degenerative processes within each 3D-culture could be monitored and analyzed.
      More strikingly, tau-specific regenerative effects caused by tau-focused active
      pharmaceutical ingredients could be quantitatively monitored by impedance
      spectroscopy.Bringing together our novel complex 3D cell culture taupathology
      model and our microcavity array-based impedimetric measurement system, we provide
      a powerful tool for the label-free investigation of tau-related pathology
      processes as well as the high content analysis of potential active pharmaceutical
      ingredient candidates.

PMID- 23145104
TI  - Tracking taphonomic regimes using chemical and mechanical damage of pollen and
      spores: an example from the Triassic-Jurassic mass extinction.
AB  - The interpretation of biotic changes in the geological past relies on the
      assumption that samples from different time intervals represent an equivalent
      suite of natural sampling conditions. As a result, detailed investigations of
      taphonomic regimes during intervals of major biotic upheaval, such as mass
      extinctions, are crucial. In this paper, we have used variations in the frequency
      of chemical and mechanical sporomorph (pollen and spore) damage as a guide to
      taphonomic regimes across the Triassic-Jurassic mass extinction (Tr-J; ~201.3 Ma)
      at a boundary section at Astartekloft, East Greenland. We find that the frequency
      of sporomorph damage is extremely variable in samples from this locality. This
      likely reflects a combination of taxon-specific susceptibility to damage and the
      mixing of sporomorphs from a mosaic of environments and taphonomic regimes. The
      stratigraphic interval containing evidence of plant extinction and compositional
      change in the source vegetation at Astartekloft is not marked by a consistent
      rise or fall in the frequency of sporomorph damage. This indicates that natural
      taphonomic regimes did not shift radically during this critical interval. We find
      no evidence of a consistent relationship between the taxonomic richness of
      sporomorph assemblages and the frequency of damage among sporomorphs at
      Astartekloft. This indicates that previously reported patterns of sporomorph
      richness across the Tr-J at this locality are likely to be robust. Taken
      together, our results suggest that the patterns of vegetation change at
      Astartekloft represent a real biological response to environmental change at the
      Tr-J.

PMID- 23145105
TI  - Intestine-specific Mttp deletion decreases mortality and prevents sepsis-induced
      intestinal injury in a murine model of Pseudomonas aeruginosa pneumonia.
AB  - BACKGROUND: The small intestine plays a crucial role in the pathophysiology of
      sepsis and has been referred to as the "motor" of the systemic inflammatory
      response. One proposed mechanism is that toxic gut-derived lipid factors,
      transported in mesenteric lymph, induce systemic injury and distant organ
      failure. However, the pathways involved are yet to be defined and the role of
      intestinal chylomicron assembly and secretion in transporting these lipid factors
      is unknown. Here we studied the outcome of sepsis in mice with conditional,
      intestine-specific deletion of microsomal triglyceride transfer protein (Mttp
      IKO), which exhibit a block in chylomicron assembly together with lipid
      malabsorption. METHODOLOGY/PRINCIPAL FINDINGS: Mttp-IKO mice and controls
      underwent intratracheal injection with either Pseudomonas aeruginosa or sterile
      saline. Mttp-IKO mice exhibited decreased seven-day mortality, with 0/20 (0%)
      dying compared to 5/17 (29%) control mice (p<0.05). This survival advantage in
      Mttp-IKO mice, however, was not associated with improvements in pulmonary
      bacterial clearance or neutrophil infiltration. Rather, Mttp-IKO mice exhibited
      protection against sepsis-associated decreases in villus length and intestinal
      proliferation and were also protected against increased intestinal apoptosis,
      both central features in control septic mice. Serum IL-6 levels, a major
      predictor of mortality in human and mouse models of sepsis, were elevated 8-fold
      in septic control mice but remained unaltered in septic Mttp-IKO mice. Serum high
      density lipoprotein (HDL) levels were reduced in septic control mice but were
      increased in septic Mttp-IKO mice. The decreased levels of HDL were associated
      with decreased hepatic expression of apolipoprotein A1 in septic control mice.
      CONCLUSIONS/SIGNIFICANCE: These studies suggest that strategies directed at
      blocking intestinal chylomicron secretion may attenuate the progression and
      improve the outcome of sepsis through effects mediated by metabolic and
      physiological adaptations in both intestinal and hepatic lipid flux.

PMID- 23145107
TI  - What are the proteolytic enzymes of honey and what they do tell us? A fingerprint
      analysis by 2-D zymography of unifloral honeys.
AB  - Honey is a sweet and healthy food produced by honeybees (Apis mellifera L.) from
      flower nectars. Using bidimensional zymography, we have detected the, until now
      unrevealed, proteolytic activities present in row honey samples. The resulting
      zymograms were specific for each type of the four unifloral honey under study,
      and enzymes were identified as serine proteases by the use of specific
      inhibitors. Further, using bidimensional electrophoresis, we have shown that
      honey proteases are able to degrade the major Royal Jelly proteins and in
      particular MRPJ-1, the protein that promotes queen differentiation in honeybees.
      Our findings open new perspectives for the better understanding of honeybee
      development, social behaviour and role in honey production. The now discovered
      honey proteases may influence honey properties and quality, and bidimensional
      zymograms might be useful to distinguish between different honey types, establish
      their age and floral origin, and allow honey certification.

PMID- 23145106
TI  - Cohesin is required for activation of MYC by estradiol.
AB  - Cohesin is best known as a multi-subunit protein complex that holds together
      replicated sister chromatids from S phase until G2. Cohesin also has an important
      role in the regulation of gene expression. We previously demonstrated that the
      cohesin complex positively regulates expression of the oncogene MYC. Cell
      proliferation driven by MYC contributes to many cancers, including breast cancer.
      The MYC oncogene is estrogen-responsive and a transcriptional target of estrogen
      receptor alpha (ERalpha). Estrogen-induced cohesin binding sites coincide with
      ERalpha binding at the MYC locus, raising the possibility that cohesin and
      ERalpha combine actions to regulate MYC transcription. The objective of this
      study was to investigate a putative role for cohesin in estrogen induction of MYC
      expression. We found that siRNA-targeted depletion of a cohesin subunit, RAD21,
      decreased MYC expression in ER-positive (MCF7 and T47D) and ER-negative (MDA-MB
      231) breast cancer cell lines. In addition, RAD21 depletion blocked estradiol
      mediated activation of MYC in ER-positive cell lines, and decreased ERalpha
      binding to estrogen response elements (EREs) upstream of MYC, without affecting
      total ERalpha levels. Treatment of MCF7 cells with estradiol caused enrichment of
      RAD21 binding at upstream enhancers and at the P2 promoter of MYC. Enriched
      binding at all sites, except the P2 promoter, was dependent on ERalpha. Since
      RAD21 depletion did not affect transcription driven by an exogenous reporter
      construct containing a naked ERE, chromatin-based mechanisms are likely to be
      involved in cohesin-dependent MYC transcription. This study demonstrates that
      ERalpha activation of MYC can be modulated by cohesin. Together, these results
      demonstrate a novel role for cohesin in estrogen-mediated regulation of MYC and
      the first evidence that cohesin plays a role in ERalpha binding.

PMID- 23145108
TI  - Metabolic engineering plant seeds with fish oil-like levels of DHA.
AB  - BACKGROUND: Omega-3 long-chain (>=C(20)) polyunsaturated fatty acids (omega3 LC
      PUFA) have critical roles in human health and development with studies indicating
      that deficiencies in these fatty acids can increase the risk or severity of
      cardiovascular and inflammatory diseases in particular. These fatty acids are
      predominantly sourced from fish and algal oils, but it is widely recognised that
      there is an urgent need for an alternative and sustainable source of EPA and DHA.
      Since the earliest demonstrations of omega3 LC-PUFA engineering there has been
      good progress in engineering the C(20) EPA with seed fatty acid levels similar to
      that observed in bulk fish oil (~18%), although undesirable omega6 PUFA levels
      have also remained high. METHODOLOGY/PRINCIPAL FINDINGS: The transgenic seed
      production of the particularly important C(22) DHA has been problematic with many
      attempts resulting in the accumulation of EPA/DPA, but only a few percent of DHA.
      This study describes the production of up to 15% of the C(22) fatty acid DHA in
      Arabidopsis thaliana seed oil with a high omega3/omega6 ratio. This was achieved
      using a transgenic pathway to increase the C(18) ALA which was then converted to
      DHA by a microalgal Delta6-desaturase pathway. CONCLUSIONS/SIGNIFICANCE: The
      amount of DHA described in this study exceeds the 12% level at which DHA is
      generally found in bulk fish oil. This is a breakthrough in the development of
      sustainable alternative sources of DHA as this technology should be applicable in
      oilseed crops. One hectare of a Brassica napus crop containing 12% DHA in seed
      oil would produce as much DHA as approximately 10,000 fish.

PMID- 23145109
TI  - Molecular dissection of the basal clades in the human Y chromosome phylogenetic
      tree.
AB  - One hundred and forty-six previously detected mutations were more precisely
      positioned in the human Y chromosome phylogeny by the analysis of 51
      representative Y chromosome haplogroups and the use of 59 mutations from
      literature. Twenty-two new mutations were also described and incorporated in the
      revised phylogeny. This analysis made it possible to identify new haplogroups and
      to resolve a deep trifurcation within haplogroup B2. Our data provide a highly
      resolved branching in the African-specific portion of the Y tree and support the
      hypothesis of an origin in the north-western quadrant of the African continent
      for the human MSY diversity.

PMID- 23145111
TI  - How are academic age, productivity and collaboration related to citing behavior
      of researchers?
AB  - References are an essential component of research articles and therefore of
      scientific communication. In this study we investigate referencing (citing)
      behavior in five diverse fields (astronomy, mathematics, robotics, ecology and
      economics) based on 213,756 core journal articles. At the macro level we find:
      (a) a steady increase in the number of references per article over the period
      studied (50 years), which in some fields is due to a higher rate of usage, while
      in others reflects longer articles and (b) an increase in all fields in the
      fraction of older, foundational references since the 1980s, with no obvious
      change in citing patterns associated with the introduction of the Internet. At
      the meso level we explore current (2006-2010) referencing behavior of different
      categories of authors (21,562 total) within each field, based on their academic
      age, productivity and collaborative practices. Contrary to some previous findings
      and expectations we find that senior researchers use references at the same rate
      as their junior colleagues, with similar rates of re-citation (use of same
      references in multiple papers). High Modified Price Index (MPI, which measures
      the speed of the research front more accurately than the traditional Price Index)
      of senior authors indicates that their research has the similar cutting-edge
      aspect as that of their younger colleagues. In all fields both the productive
      researchers and especially those who collaborate more use a significantly lower
      fraction of foundational references and have much higher MPI and lower re
      citation rates, i.e., they are the ones pushing the research front regardless of
      researcher age. This paper introduces improved bibliometric methods to measure
      the speed of the research front, disambiguate lead authors in co-authored papers
      and decouple measures of productivity and collaboration.

PMID- 23145110
TI  - Subcellular localization of p44/WDR77 determines proliferation and
      differentiation of prostate epithelial cells.
AB  - The molecular mechanism that controls the proliferation and differentiation of
      prostate epithelial cells is currently unknown. We previously identified a 44-kDa
      protein (p44/wdr77) as an androgen receptor-interacting protein that regulates a
      set of androgen receptor target genes in prostate epithelial cells and prostate
      cancer. In this study, we found that p44 localizes in the cytoplasm of prostate
      epithelial cells at the early stage of prostate development when cells are
      proliferating, and its nuclear translocation is associated with cellular and
      functional differentiation in adult prostate tissue. We further demonstrated that
      cytoplasmic p44 protein is essential for proliferation of prostate epithelial
      cells, whereas nuclear p44 is required for cell differentiation and prostate-
      specific protein secretion. These studies suggest a novel mechanism by which
      proliferation and differentiation of prostate epithelial cells are controlled by
      p44's location in the cell.

PMID- 23145112
TI  - Mechanism of selective VEGF-A binding by neuropilin-1 reveals a basis for
      specific ligand inhibition.
AB  - Neuropilin (Nrp) receptors function as essential cell surface receptors for the
      Vascular Endothelial Growth Factor (VEGF) family of proangiogenic cytokines and
      the semaphorin 3 (Sema3) family of axon guidance molecules. There are two Nrp
      homologues, Nrp1 and Nrp2, which bind to both overlapping and distinct members of
      the VEGF and Sema3 family of molecules. Nrp1 specifically binds the VEGF-A(164/5)
      isoform, which is essential for developmental angiogenesis. We demonstrate that
      VEGF-A specific binding is governed by Nrp1 residues in the b1 coagulation factor
      domain surrounding the invariant Nrp C-terminal arginine binding pocket. Further,
      we show that Sema3F does not display the Nrp-specific binding to the b1 domain
      seen with VEGF-A. Engineered soluble Nrp receptor fragments that selectively
      sequester ligands from the active signaling complex are an attractive modality
      for selectively blocking the angiogenic and chemorepulsive functions of Nrp
      ligands. Utilizing the information on Nrp ligand binding specificity, we
      demonstrate Nrp constructs that specifically sequester Sema3 in the presence of
      VEGF-A. This establishes that unique mechanisms are used by Nrp receptors to
      mediate specific ligand binding and that these differences can be exploited to
      engineer soluble Nrp receptors with specificity for Sema3.

PMID- 23145113
TI  - A questionnaire elicitation of surgeons' belief about learning within a surgical
      trial.
AB  - INTRODUCTION: Surgeons gain expertise as they repeatedly conduct a procedure.
      Such learning is widely acknowledged to pose a challenge to evaluating new
      surgical procedures. Most surgical trials report little if any information on
      learning. We elicited surgeons' belief regarding learning within the context of a
      randomised trial which assessed two surgical procedures. MATERIALS AND METHODS:
      Surgeons participating in the UKUFF trial were sent a postal questionnaire
      requesting details on current practice, prior experience and their belief
      regarding acquiring proficiency and the learning curve of operation time for two
      surgical procedures (open and arthroscopic rotator cuff repair). RESULTS: In
      total 52 (58%) participating surgeons returned a completed questionnaire. The
      median (IQR) number of procedures required to acquire proficiency were 17 (10,23)
      and 35 (23,50) for the open and arthroscopic repairs respectively. The
      distribution of surgeons' belief regarding the initial point had median (IQR) of
      109 (69,128) and 145 (97,171) minutes for open and arthroscopic repair
      respectively. Corresponding values for the plateau point were 60 (46, 82) and 79
      (58, 110). CONCLUSIONS: We have shown that information on the current practice,
      prior experience and beliefs on the learning process of a surgical procedure can
      be elicited using a short questionnaire. The approach could aid the
      interpretation of trial results in terms of generalisability and be used a priori
      in the design of a trial.

PMID- 23145114
TI  - Overview on the diversity of sounds produced by clownfishes (Pomacentridae):
      importance of acoustic signals in their peculiar way of life.
AB  - BACKGROUND: Clownfishes (Pomacentridae) are brightly colored coral reef fishes
      well known for their mutualistic symbiosis with tropical sea anemones. These
      fishes live in social groups in which there is a size-based dominance hierarchy.
      In this structure where sex is socially controlled, agonistic interactions are
      numerous and serve to maintain size differences between individuals adjacent in
      rank. Clownfishes are also prolific callers whose sounds seem to play an
      important role in the social hierarchy. Here, we aim to review and to synthesize
      the diversity of sounds produced by clownfishes in order to emphasize the
      importance of acoustic signals in their way of life. METHODOLOGY/PRINCIPAL
      FINDINGS: Recording the different acoustic behaviors indicated that sounds are
      divided into two main categories: aggressive sounds produced in conjunction with
      threat postures (charge and chase), and submissive sounds always emitted when
      fish exhibited head shaking movements (i.e. a submissive posture). Both types of
      sounds showed size-related intraspecific variation in dominant frequency and
      pulse duration: smaller individuals produce higher frequency and shorter duration
      pulses than larger ones, and inversely. Consequently, these sonic features might
      be useful cues for individual recognition within the group. This observation is
      of significant importance due to the size-based hierarchy in clownfish group. On
      the other hand, no acoustic signal was associated with the different reproductive
      activities. CONCLUSIONS/SIGNIFICANCE: Unlike other pomacentrids, sounds are not
      produced for mate attraction in clownfishes but to reach and to defend the
      competition for breeding status, which explains why constraints are not important
      enough for promoting call diversification in this group.

PMID- 23145115
TI  - Effectiveness of ultra-low volume nighttime applications of an adulticide against
      diurnal Aedes albopictus, a critical vector of dengue and chikungunya viruses.
AB  - Aedes albopictus, the Asian tiger mosquito, continues expanding its geographic
      range and involvement in mosquito-borne diseases such as chikungunya and dengue.
      Vector control programs rarely attempt to suppress this diurnal species with an
      ultra-low volume (ULV) adulticide because for maximum efficacy applications are
      conducted at night. During 2009-2011 we performed experimental nighttime
      applications of a novel adulticide (DUET(r)) against field populations of Ae.
      albopictus within an urban site composed of approximately 1,000 parcels (home and
      yard) in northeastern USA. Dual applications at mid label rate of the adulticide
      spaced one or two days apart accomplished significantly higher control (85.0 +/-
      5.4% average reduction) than single full rate applications (73.0 +/- 5.4%). Our
      results demonstrate that nighttime ULV adulticiding is effective in reducing Ae.
      albopictus abundance and highlight its potential for use as part of integrated
      pest management programs and during disease epidemics when reducing human illness
      is of paramount importance.

PMID- 23145116
TI  - Soft x-ray irradiation effects of Li2O2, Li2CO3 and Li2O revealed by absorption
      spectroscopy.
AB  - Li(2)O(2), Li(2)CO(3), and Li(2)O are three critical compounds in lithium-air and
      lithium-ion energy storage systems. Extensive measurements have been carried out
      to study the chemical species and their evolutions at difference stages of the
      device operation. While x-ray spectroscopy has been demonstrated to be one of the
      most powerful tools for such purpose, no systematic study on the irradiation
      effects have been reported. Here we carry out extensive time, position, and
      irradiation dependent Li K-edge soft x-ray absorption spectroscopy on these
      compounds with so far the best energy resolution. The ultra-high resolution in
      the current study allows the features in the absorption spectra to be well
      resolved. The spectral lineshape thus serves as the fingerprints of these
      compounds, enabling the tracking of their evolution under x-ray irradiation. We
      found that both Li(2)O(2) and Li(2)CO(3) evidently evolve towards Li(2)O under
      the soft x-ray irradiation with Li(2)CO(3) exhibiting a surprisingly higher
      sensitivity to x-rays than Li(2)O(2). On the other hand, Li(2)O remains the most
      stable compound despite experiencing substantial irradiation dose. We thus
      conclude that high resolution soft x-ray spectroscopy could unambiguously
      fingerprint different chemical species, but special cautions on irradiation
      effects would be needed in performing the experiments and interpreting the data
      properly.

PMID- 23145117
TI  - BLT2 up-regulates interleukin-8 production and promotes the invasiveness of
      breast cancer cells.
AB  - BACKGROUND: The elevated production of interleukin (IL)-8 is critically
      associated with invasiveness and metastatic potential in breast cancer cells.
      However, the intracellular signaling pathway responsible for up-regulation of IL
      8 production in breast cancer cells has remained unclear. METHODOLOGY/PRINCIPAL
      FINDINGS: In this study, we report that the expression of BLT2 is markedly up
      regulated in the highly aggressive human breast cancer cell lines MDA-MB-231 and
      MDA-MB-435 compared with MCF-10A immortalized human mammary epithelial cells, as
      determined by RT-PCR, real-time PCR and FACS analysis. Blockade of BLT2 with BLT2
      siRNA knockdown or BLT2 inhibitor treatment downregulated IL-8 production and
      thereby diminished the invasiveness of aggressive breast cancer cells, analyzed
      by Matrigel invasion chamber assays. We further characterized the downstream
      signaling mechanism by which BLT2 stimulates IL-8 production and identified
      critical mediatory roles for the generation of reactive oxygen species (ROS) and
      the consequent activation of the transcription factor NF-kappaB. Moreover,
      blockade of BLT2 suppressed the formation of metastatic lung nodules by MDA-MB
      231 cells in both experimental and orthotopic metastasis models.
      CONCLUSIONS/SIGNIFICANCE: Taken together, our study demonstrates that a BLT2-ROS
      NF-kappaB pathway up-regulates IL-8 production in MDA-MB-231 and MDA-MB-435
      cells, thereby contributing to the invasiveness of these aggressive breast cancer
      cells. Our findings provide insight into the molecular mechanism of invasiveness
      in breast cancer.

PMID- 23145118
TI  - Processing of Chlamydia abortus polymorphic membrane protein 18D during the
      chlamydial developmental cycle.
AB  - BACKGROUND: Chlamydia possess a unique family of autotransporter proteins known
      as the Polymorphic membrane proteins (Pmps). While the total number of pmp genes
      varies between Chlamydia species, all encode a single pmpD gene. In both
      Chlamydia trachomatis (C. trachomatis) and C. pneumoniae, the PmpD protein is
      proteolytically cleaved on the cell surface. The current study was carried out to
      determine the cleavage patterns of the PmpD protein in the animal pathogen C.
      abortus (termed Pmp18D). METHODOLOGY/PRINCIPAL FINDINGS: Using antibodies
      directed against different regions of Pmp18D, proteomic techniques revealed that
      the mature protein was cleaved on the cell surface, resulting in a100 kDa N
      terminal product and a 60 kDa carboxy-terminal protein. The N-terminal protein
      was further processed into 84, 76 and 73 kDa products. Clustering analysis
      resolved PmpD proteins into three distinct clades with C. abortus Pmp18D, being
      most similar to those originating from C. psittaci, C. felis and C. caviae.
      CONCLUSIONS/SIGNIFICANCE: This study indicates that C. abortus Pmp18D is
      proteolytically processed at the cell surface similar to the proteins of C.
      trachomatis and C. pneumoniae. However, patterns of cleavage are species
      specific, with low sequence conservation of PmpD across the genus. The absence of
      conserved domains indicates that the function of the PmpD molecule in chlamydia
      remains to be elucidated.

PMID- 23145119
TI  - Caprylic triglyceride as a novel therapeutic approach to effectively improve the
      performance and attenuate the symptoms due to the motor neuron loss in ALS
      disease.
AB  - Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder of motor
      neurons causing progressive muscle weakness, paralysis, and finally death. ALS
      patients suffer from asthenia and their progressive weakness negatively impacts
      quality of life, limiting their daily activities. They have impaired energy
      balance linked to lower activity of mitochondrial electron transport chain
      enzymes in ALS spinal cord, suggesting that improving mitochondrial function may
      present a therapeutic approach for ALS. When fed a ketogenic diet, the G93A ALS
      mouse shows a significant increase in serum ketones as well as a significantly
      slower progression of weakness and lower mortality rate. In this study, we
      treated SOD1-G93A mice with caprylic triglyceride, a medium chain triglyceride
      that is metabolized into ketone bodies and can serve as an alternate energy
      substrate for neuronal metabolism. Treatment with caprylic triglyceride
      attenuated progression of weakness and protected spinal cord motor neuron loss in
      SOD1-G93A transgenic animals, significantly improving their performance even
      though there was no significant benefit regarding the survival of the ALS
      transgenic animals. We found that caprylic triglyceride significantly promoted
      the mitochondrial oxygen consumption rate in vivo. Our results demonstrated that
      caprylic triglyceride alleviates ALS-type motor impairment through restoration of
      energy metabolism in SOD1-G93A ALS mice, especially during the overt stage of the
      disease. These data indicate the feasibility of using caprylic acid as an easily
      administered treatment with a high impact on the quality of life of ALS patients.

PMID- 23145120
TI  - Effects of the CK2 inhibitors CX-4945 and CX-5011 on drug-resistant cells.
AB  - CK2 is a pleiotropic protein kinase, which regulates many survival pathways and
      plays a global anti-apoptotic function. It is highly expressed in tumor cells,
      and is presently considered a promising therapeutic target. Among the many
      inhibitors available for this kinase, the recently developed CX-4945 and CX-5011
      have proved to be very potent, selective and effective in inducing cell death in
      tumor cells; CX-4945 has recently entered clinical trials. However, no data are
      available on the efficacy of these compounds to overcome drug resistance, a major
      reasons of cancer therapy failure. Here we address this point, by studying their
      effects in several tumor cell lines, each available as variant R resistant to
      drug-induced apoptosis, and normal-sensitive variant S. We found that the
      inhibition of endogenous CK2 was very similar in S and R treated cells, with more
      than 50% CK2 activity reduction at sub-micromolar concentrations of CX-4945 and
      CX-5011. A consequent apoptotic response was induced both in S and R variants of
      each pairs. Moreover, the combined treatment of CX-4945 plus vinblastine was able
      to sensitize to vinblastine R cells that are otherwise almost insensitive to this
      conventional antitumor drug. Consistently, doxorubicin accumulation in multidrug
      resistant (MDR) cells was greatly increased by CX-4945.In summary, we
      demonstrated that all the R variants are sensitive to CX-4945 and CX-5011; since
      some of the treated R lines express the extrusion pump Pgp, often responsible of
      the MDR phenotype, we can also conclude that the two inhibitors can successfully
      overcome the MDR phenomenon.

PMID- 23145121
TI  - Luteolin induces carcinoma cell apoptosis through binding Hsp90 to suppress
      constitutive activation of STAT3.
AB  - BACKGROUND: Abnormal activity of STAT3 is associated with a number of human
      malignancies. Hsp90 plays a central role in stabilizing newly synthesized
      proteins and participates in maintaining the functional competency of a number of
      signaling transducers involved in cell growth, survival and oncogenesis, such as
      STAT3. Hsp90 interacts with STAT3 and stabilizes Tyr-phosphorylated STAT3. It has
      been reported that luteolin possesses anticancer activity through degradation of
      Tyr(705)-phosphorylated STAT3. METHODOLOGY/PRINCIPAL FINDINGS: We found that
      overexpression of Hsp90 inhibited luteolin-induced degradation of Tyr(705)
      phosphorylated STAT3 and luteolin also reduced the levels of some other Hsp90
      interacting proteins. Results from co-immunoprecipitation and immunoblot analysis
      demonstrated that luteolin prevented the association between Hsp90 and STAT3 and
      induced both Tyr(705)- and Ser(727)-phosphorylated STAT3 degradation through
      proteasome-dependent pathway. The molecular modeling analysis with CHARMm
      Discovery Studio 2.1(DS 2.1) indicated that luteolin could bind to the ATP
      binding pocket of Hsp90. SPR technology-based binding assay confirmed the
      association between luteolin and Hsp90. ATP-sepharose binding assay displayed
      that luteolin inhibited Hsp90-ATP binding. CONCLUSIONS/SIGNIFICANCE: Luteolin
      promoted the degradation of Tyr(705)- and Ser(727)-phosphorylated STAT3 through
      interacting with Hsp90 and induced apoptosis of cancer cells. This study
      indicated that luteolin may act as a potent HSP90 inhibitor in antitumor
      strategies.

PMID- 23145122
TI  - Ancient divergence in the trans-oceanic deep-sea shark Centroscymnus crepidater.
AB  - Unravelling the genetic structure and phylogeographic patterns of deep-sea sharks
      is particularly challenging given the inherent difficulty in obtaining samples.
      The deep-sea shark Centroscymnus crepidater is a medium-sized benthopelagic
      species that exhibits a circumglobal distribution occurring both in the Atlantic
      and Indo-Pacific Oceans. Contrary to the wealth of phylogeographic studies
      focused on coastal sharks, the genetic structure of bathyal species remains
      largely unexplored. We used a fragment of the mitochondrial DNA control region,
      and microsatellite data, to examine genetic structure in C. crepidater collected
      from the Atlantic Ocean, Tasman Sea, and southern Pacific Ocean (Chatham Rise).
      Two deeply divergent (3.1%) mtDNA clades were recovered, with one clade including
      both Atlantic and Pacific specimens, and the other composed of Atlantic samples
      with a single specimen from the Pacific (Chatham Rise). Bayesian analyses
      estimated this splitting in the Miocene at about 15 million years ago. The
      ancestral C. crepidater lineage was probably widely distributed in the Atlantic
      and Indo-Pacific Oceans. The oceanic cooling observed during the Miocene due to
      an Antarctic glaciation and the Tethys closure caused changes in environmental
      conditions that presumably restricted gene flow between basins. Fluctuations in
      food resources in the Southern Ocean might have promoted the dispersal of C.
      crepidater throughout the northern Atlantic where habitat conditions were more
      suitable during the Miocene. The significant genetic structure revealed by
      microsatellite data suggests the existence of present-day barriers to gene flow
      between the Atlantic and Pacific populations most likely due to the influence of
      the Agulhas Current retroflection on prey movements.

PMID- 23145123
TI  - Next-generation cDNA screening for oncogene and resistance phenotypes.
AB  - There is a pressing need for methods to define the functional relevance of
      genetic alterations identified by next-generation sequencing of cancer specimens.
      We developed new approaches to efficiently construct full-length cDNA libraries
      from small amounts of total RNA, screen for transforming and resistance
      phenotypes, and deconvolute by next-generation sequencing. Using this platform,
      we screened a panel of cDNA libraries from primary specimens and cell lines in
      cytokine-dependent murine Ba/F3 cells. We demonstrate that cDNA library-based
      screening can efficiently identify DNA and RNA alterations that confer either
      cytokine-independent proliferation or resistance to targeted inhibitors,
      including RNA alterations and intergenic fusions. Using barcoded next-generation
      sequencing, we simultaneously deconvoluted cytokine-independent clones recovered
      after transduction of 21 cDNA libraries. This approach identified multiple gain
      of-function alleles, including KRAS G12D, NRAS Q61K and an activating splice
      variant of ERBB2. This approach has broad applicability for identifying
      transcripts that confer proliferation, resistance and other phenotypes in vitro
      and potentially in vivo.

PMID- 23145124
TI  - AHCYL1 is mediated by estrogen-induced ERK1/2 MAPK cell signaling and microRNA
      regulation to effect functional aspects of the avian oviduct.
AB  - S-adenosylhomocysteine hydrolase-like protein 1 (AHCYL1), also known as IP(3)
      receptor-binding protein released with IP(3) (IRBIT), regulates IP(3)-induced
      Ca(2+) release into the cytoplasm of cells. AHCYL1 is a critical regulator of
      early developmental stages in zebrafish, but little is known about the function
      of AHCYL1 or hormonal regulation of expression of the AHCYL1 gene in avian
      species. Therefore, we investigated differential expression profiles of the
      AHCYL1 gene in various adult organs and in oviducts from estrogen-treated
      chickens. Chicken AHCYL1 encodes for a protein of 540 amino acids that is highly
      conserved and has considerable homology to mammalian AHCYL1 proteins (>94%
      identity). AHCYL1 mRNA was expressed abundantly in various organs of chickens.
      Further, the synthetic estrogen agonist induced AHCYL1 mRNA and protein
      predominantly in luminal and glandular epithelial cells of the chick oviduct. In
      addition, estrogen activated AHCYL1 through the ERK1/2 signal transduction
      cascade and that activated expression of AHCYL1 regulated genes affecting oviduct
      development in chicks as well as calcium release in epithelial cells of the
      oviduct. Also, microRNAs, miR-124a, miR-1669, miR-1710 and miR-1782 influenced
      AHCYL1 expression in vitro via its 3'-UTR which suggests that post
      transcriptional events are involved in the regulation of AHCYL1 expression in the
      chick oviduct. In conclusion, these results indicate that AHCYL1 is a novel
      estrogen-stimulated gene expressed in epithelial cells of the chicken oviduct
      that likely affects growth, development and calcium metabolism of the mature
      oviduct of hens via an estrogen-mediated ERK1/2 MAPK cell signaling pathway.

PMID- 23145125
TI  - Telomere length variation in juvenile acute myocardial infarction.
AB  - Leukocyte telomere length (LTL) provides a potential marker of biological age,
      closely related to the endothelial dysfunction and consequently to the
      atherosclerotic process. To investigate the relationship between the LTL and the
      risk of premature acute myocardial infarction and to evaluate the predictive
      value of LTL on the onset of major cardiovascular events, 199 patients from 18 to
      48 years old with first diagnosis of acute myocardial infarction were enrolled
      and were matched with 190 controls for sex and age (+/- 1 year). Clinical data
      and coronary artery disease were evaluated at enrollment and at follow up. LTL
      was measured at enrollment using a quantitative PCR-based method. No significant
      differences were observed in LTL between cases and controls (p = 0.20) and with
      the presence of coronary artery disease in patients (p = 0.47).
      Hypercholesterolemic cases presented LTL significantly longer than cases without
      hypercholesterolemia (t/s: 0.82 +/- 0.16 p = 0.79 and t/s norm: 0.79 +/- 0.19 p =
      0.01), as confirmed in multivariate regression analysis (p = 0.005, beta = 0.09).
      Furthermore, multivariate regression analysis showed LTL significantly shorter in
      hypertensive cases than in normotensive cases (p = 0.04, beta = -0.07). One
      hundred seventy-one cases (86%) ended the average follow up of 9 +/- 5 years, 92
      (54%) presented a major cardiovascular event. At multivariate regression analysis
      the LTL detected at enrollment did not represent a predictive factor of major
      cardiovascular events nor it significantly impacted with cumulative events. Based
      on present cohort of young Italian patients, the LTL did not represent a marker
      of acute myocardial infarction nor had a predictive role at medium term follow
      up.

PMID- 23145126
TI  - Prospectively versus retrospectively ECG-gated 256-slice CT angiography to assess
      coronary artery bypass grafts--comparison of image quality and radiation dose.
AB  - OBJECTIVE: In this retrospective non-randomized cohort study, the image quality
      and radiation dose were compared between prospectively electrocardiogram (ECG)
      gated axial (PGA) and retrospectively ECG-gated helical (RGH) techniques for the
      assessment of coronary artery bypass grafts using 256-slice CT. METHODS: We
      studied 124 grafts with 577 segments in 64 patients with a heart rate (HR) <85
      bpm who underwent CT coronary angiography (CTCA); 34 patients with RGH-CTCA and
      30 patients with PGA-CTCA. The image quality of the bypass grafts was assessed by
      a 5-point scale (1 = excellent to 5 = non-diagnostic) for each segment (proximal
      anastomosis, proximal, middle, distal course of graft body, and distal
      anastomosis). Other objective image quality indices such as noise, signal-to
      noise ratio (SNR) and contrast-to-noise ratios (CNR) were assessed. Radiation
      doses were also compared. RESULTS: Patient characteristics of the two groups were
      well matched except HR. The HR of the PGA group was lower than that of the RGH
      group (62.0 +/- 5.0 vs. 65.7 +/- 7.4). For both groups, over 90% of segments
      received excellent or good image quality scores and none was non-evaluative. The
      image quality generally degraded as graft segment approached to distal
      anastomosis regardless of techniques and graft types. Image quality scores of the
      PGA group were better than those of the RGH group (1.51 +/- 0.53 vs. 1.73 +/-
      0.62; p<0.001). There was no significantly difference of objective image quality
      between two techniques, and the effective radiation dose was significantly lower
      in the PGA group (7.0 +/- 1.2 mSv) than that of the RGH group (20.0 +/- 4.6 mSv)
      (p<0.001), with a 65.0% dose reduction. CONCLUSIONS: Following bypass surgery,
      256-slice PGA-CTCA is superior to RGH-CTCA in limiting the radiation dose and
      obtaining better image quality for bypass grafts.

PMID- 23145127
TI  - Evaluating the effect of therapeutic stem cells on TRAIL resistant and sensitive
      medulloblastomas.
AB  - Mesenchymal stem cells (MSC) are emerging as novel cell-based delivery agents;
      however, a thorough investigation addressing their therapeutic potential in
      medulloblastomas (MB) has not been explored to date. In this study, we engineered
      human MSC to express a potent and secretable variant of a tumor specific agent,
      tumor necrosis factor-apoptosis-inducing ligand (S-TRAIL) and assessed the
      ability of MSC-S-TRAIL mediated MB killing alone or in combination with a small
      molecule inhibitor of histone-deacetylase, MS-275, in TRAIL-sensitive and 
      resistant MB in vitro and in vivo. We show that TRAIL sensitivity/resistance
      correlates with the expression of its cognate death receptor (DR)5 and MSC-S
      TRAIL induces caspase-3 mediated apoptosis in TRAIL-sensitive MB lines. In TRAIL
      resistant MB, we show upregulation of DR4/5 levels when pre-treated with MS-275
      and a subsequent sensitization to MSC-S-TRAIL mediated apoptosis. Using
      intracranially implanted MB and MSC lines engineered with different combinations
      of fluorescent and bioluminescent proteins, we show that MSC-S-TRAIL has
      significant anti-tumor effects in mice bearing TRAIL-sensitive and MS-275 pre
      treated TRAIL-resistant MBs. To our knowledge, this is the first study that
      explores the use of human MSC as MB-targeting therapeutic-vehicles in vivo in
      TRAIL-sensitive and resistant tumors, and has implications for developing
      effective therapies for patients with medulloblastomas.

PMID- 23145128
TI  - Tissue turnover rates and isotopic trophic discrimination factors in the
      endothermic teleost, pacific bluefin tuna (Thunnus orientalis).
AB  - Stable isotope analysis (SIA) of highly migratory marine pelagic animals can
      improve understanding of their migratory patterns and trophic ecology. However,
      accurate interpretation of isotopic analyses relies on knowledge of isotope
      turnover rates and tissue-diet isotope discrimination factors. Laboratory-derived
      turnover rates and discrimination factors have been difficult to obtain due to
      the challenges of maintaining these species in captivity. We conducted a study to
      determine tissue- (white muscle and liver) and isotope- (nitrogen and carbon)
      specific turnover rates and trophic discrimination factors (TDFs) using archived
      tissues from captive Pacific bluefin tuna (PBFT), Thunnus orientalis, 1-2914 days
      after a diet shift in captivity. Half-life values for (15)N turnover in white
      muscle and liver were 167 and 86 days, and for (13)C were 255 and 162 days,
      respectively. TDFs for white muscle and liver were 1.9 and 1.10/00 for delta(15)N
      and 1.8 and 1.20/00 for delta(13)C, respectively. Our results demonstrate that
      turnover of (15)N and (13)C in bluefin tuna tissues is well described by a single
      compartment first-order kinetics model. We report variability in turnover rates
      between tissue types and their isotope dynamics, and hypothesize that metabolic
      processes play a large role in turnover of nitrogen and carbon in PBFT white
      muscle and liver tissues. (15)N in white muscle tissue showed the most
      predictable change with diet over time, suggesting that white muscle delta(15)N
      data may provide the most reliable inferences for diet and migration studies
      using stable isotopes in wild fish. These results allow more accurate
      interpretation of field data and dramatically improve our ability to use stable
      isotope data from wild tunas to better understand their migration patterns and
      trophic ecology.

PMID- 23145129
TI  - Loss of NF1 expression in human endothelial cells promotes autonomous
      proliferation and altered vascular morphogenesis.
AB  - Neurofibromatosis is a well known familial tumor syndrome, however these patients
      also suffer from a number of vascular anomalies. The loss of NFl from the
      endothelium is embryonically lethal in mouse developmental models, however little
      is known regarding the molecular regulation by NF1 in endothelium. We
      investigated the consequences of losing NF1 expression on the function of
      endothelial cells using shRNA. The loss of NF1 was sufficient to elevate levels
      of active Ras under non-stimulated conditions. These elevations in Ras activity
      were associated with activation of downstream signaling including activation of
      ERK, AKT and mTOR. Cells knocked down in NF1 expression exhibited no cellular
      senescence. Rather, they demonstrated augmented proliferation and autonomous
      entry into the cell cycle. These proliferative changes were accompanied by
      enhanced expression of cyclin D, phosphorylation of p27(KIP), and decreases in
      total p27(KIP) levels, even under growth factor free conditions. In addition, NF1
      deficient cells failed to undergo normal branching morphogenesis in a co-culture
      assay, instead forming planar islands with few tubules and branches. We find the
      changes induced by the loss of NF1 could be mitigated by co-expression of the GAP
      related domain of NF1 implicating Ras regulation in these effects. Using
      doxycycline-inducible shRNA, targeting NF1, we find that the morphogenic changes
      are reversible. Similarly, in fully differentiated and stable vascular-like
      structures, the silencing of NF1 results in the appearance of abnormal vascular
      structures. Finally, the proliferative changes and the abnormal vascular
      morphogenesis are normalized by low-dose rapamycin treatment. These data provide
      a detailed analysis of the molecular and functional consequences of NF1 loss in
      human endothelial cells. These insights may provide new approaches to
      therapeutically addressing vascular abnormalities in these patients while
      underscoring a critical role for normal Ras regulation in maintaining the health
      and function of the vasculature.

PMID- 23145130
TI  - The nutritional content of prey affects the foraging of a generalist arthropod
      predator.
AB  - While foraging theory predicts that predatory responses should be determined by
      the energy content and size of prey, it is becoming increasingly clear that
      carnivores regulate their intake of specific nutrients. We tested the hypothesis
      that prey nutrient composition and predator nutritional history affects foraging
      intensity, consumption, and prey selection by the wolf spider, Pardosa milvina.
      By altering the rearing environment for fruit flies, Drosophila melanogaster, we
      produced high quality flies containing more nitrogen and protein and less lipid
      than low quality fruit flies. In one experiment, we quantified the proportion of
      flies taken and consumption across a range of densities of either high or low
      quality flies and, in a second experiment, we determined the prey capture and
      consumption of spiders that had been maintained on contrasting diets prior to
      testing. In both cases, the proportion of prey captured declined with increasing
      prey density, which characterizes the Type II functional response that is typical
      of wolf spiders. Spiders with similar nutritional histories killed similar
      numbers of each prey type but consumed more of the low quality prey. Spiders
      provided high quality prey in the weeks prior to testing killed more prey than
      those on the low quality diet but there was no effect of prior diet on
      consumption. In the third experiment, spiders were maintained on contrasting
      diets for three weeks and then allowed to select from a mixture of high and low
      quality prey. Interestingly, feeding history affected prey preferences: spiders
      that had been on a low quality diet showed no preference but those on the high
      quality diet selected high quality flies from the mixture. Our results suggest
      that, even when prey size and species identity are controlled, the nutritional
      experience of the predator as well as the specific content of the prey shapes
      predator-prey interactions.

PMID- 23145132
TI  - Genetic PEGylation.
AB  - Polyethylene glycol (PEG) was genetically incorporated into a polypeptide. Stop
      anticodon-containing tRNAs were acylated with PEG-containing amino acids and were
      then translated into polypeptides corresponding to DNA sequences containing the
      stop codons. The molecular weights of the PEG used were 170, 500, 700, 1000, and
      2000 Da, and the translation was confirmed by mass spectrometry. The PEG
      incorporation ratio decreased as the molecular weight of PEG increased, and PEG
      with a molecular weight of 1000 Da was only slightly incorporated. Although
      improvement is required to increase the efficiency of the process, this study
      demonstrates the possibility of genetic PEGylation.

PMID- 23145131
TI  - The PDZ protein GIPC regulates trafficking of the LPA1 receptor from APPL
      signaling endosomes and attenuates the cell's response to LPA.
AB  - Lysophosphatidic acid (LPA) mediates diverse cellular responses through the
      activation of at least six LPA receptors--LPA(1-6,) but the interacting proteins
      and signaling pathways that mediate the specificity of these receptors are
      largely unknown. We noticed that LPA(1) contains a PDZ binding motif (SVV)
      identical to that present in two other proteins that interact with the PDZ
      protein GIPC. GIPC is involved in endocytic trafficking of several receptors
      including TrkA, VEGFR2, lutropin and dopamine D2 receptors. Here we show that
      GIPC binds directly to the PDZ binding motif of LPA(1) but not that of other LPA
      receptors. LPA(1) colocalizes and coimmunoprecipitates with GIPC and its binding
      partner APPL, an activator of Akt signaling found on APPL signaling endosomes.
      GIPC depletion by siRNA disturbed trafficking of LPA(1) to EEA1 early endosomes
      and promoted LPA(1) mediated Akt signaling, cell proliferation, and cell
      motility. We propose that GIPC binds LPA(1) and promotes its trafficking from
      APPL-containing signaling endosomes to EEA1 early endosomes and thus attenuates
      LPA-mediated Akt signaling from APPL endosomes.

PMID- 23145133
TI  - Nucleolin participates in DNA double-strand break-induced damage response through
      MDC1-dependent pathway.
AB  - H2AX is an important factor for chromatin remodeling to facilitate accumulation
      of DNA damage-related proteins at DNA double-strand break (DSB) sites. In order
      to further understand the role of H2AX in the DNA damage response (DDR), we
      attempted to identify H2AX-interacting proteins by proteomics analysis. As a
      result, we identified nucleolin as one of candidates. Here, we show a novel role
      of a major nucleolar protein, nucleolin, in DDR. Nucleolin interacted with gamma
      H2AX and accumulated to laser micro-irradiated DSB damage sites. Chromatin
      Immunoprecipitation assay also displayed the accumulation of nucleolin around DSB
      sites. Nucleolin-depleted cells exhibited repression of both ATM-dependent
      phosphorylation following exposure to gamma-ray and subsequent cell cycle
      checkpoint activation. Furthermore, nucleolin-knockdown reduced HR and NHEJ
      activity and showed decrease in IR-induced chromatin accumulation of HR/NHEJ
      factors, agreeing with the delayed kinetics of gamma-H2AX focus. Moreover,
      nucleolin-knockdown decreased MDC1-related events such as focus formation of 53
      BP1, RNF168, phosphorylated ATM, and H2A ubiquitination. Nucleolin also showed
      FACT-like activity for DSB damage-induced histone eviction from chromatin. Taken
      together, nucleolin could promote both ATM-dependent cell cycle checkpoint and
      DSB repair by functioning in an MDC1-related pathway through its FACT-like
      function.

PMID- 23145134
TI  - Mid-gestational gene expression profile in placenta and link to pregnancy
      complications.
AB  - Despite the importance of placenta in mediating rapid physiological changes in
      pregnancy, data on temporal dynamics of placental gene expression are limited. We
      completed the first transcriptome profiling of human placental gene expression
      dynamics (GeneChips, Affymetrix(r); ~47,000 transcripts) from early to mid
      gestation (n = 10; gestational weeks 5-18) and report 154 genes with significant
      transcriptional changes (ANOVA, FDR P<0.1). TaqMan RT-qPCR analysis (n = 43;
      gestational weeks 5-41) confirmed a significant (ANOVA and t-test, FDR P<0.05)
      mid-gestational peak of placental gene expression for BMP5, CCNG2, CDH11, FST,
      GATM, GPR183, ITGBL1, PLAGL1, SLC16A10 and STC1, followed by sharp decrease in
      mRNA levels at term (t-test, FDR P<0.05). We hypothesized that normal course of
      late pregnancy may be affected when genes characteristic to mid-gestation
      placenta remain highly expressed until term, and analyzed their expression in
      term placentas from normal and complicated pregnancies [preeclampsia (PE), n =
      12; gestational diabetes mellitus (GDM), n = 12; small- and large-for-gestational
      age newborns (SGA, LGA), n = 12+12]. STC1 (stanniocalcin 1) exhibited increased
      mRNA levels in all studied complications, with the most significant effect in PE-
      and SGA-groups (t-test, FDR P<0.05). In post-partum maternal plasma, the highest
      STC1 hormone levels (ELISA, n = 129) were found in women who had developed PE and
      delivered a SGA newborn (median 731 vs 418 pg/ml in controls; ANCOVA, P =
      0.00048). Significantly higher expression (t-test, FDR P<0.05) of CCNG2 and LYPD6
      accompanied with enhanced immunostaining of the protein was detected in placental
      sections of PE and GDM cases (n = 15). Our study demonstrates the importance of
      temporal dynamics of placental transcriptional regulation across three trimesters
      of gestation. Interestingly, many genes with high expression in mid-gestation
      placenta have also been implicated in adult complex disease, promoting the
      discussion on the role of placenta in developmental programming. The discovery of
      elevated maternal plasma STC1 in pregnancy complications warrants further
      investigations of its potential as a biomarker.

PMID- 23145135
TI  - Cell penetrable humanized-VH/V(H)H that inhibit RNA dependent RNA polymerase
      (NS5B) of HCV.
AB  - NS5B is pivotal RNA dependent RNA polymerase (RdRp) of HCV and NS5B function
      interfering halts the virus infective cycle. This work aimed to produce cell
      penetrable humanized single domain antibodies (SdAb; VH/V(H)H) that interfere
      with the RdRp activity. Recombinant NS5BDelta55 of genotype 3a HCV with de novo
      RNA synthetic activity was produced and used in phage biopanning for selecting
      phage clones that displayed NS5BDelta55 bound VH/V(H)H from a humanized-camel
      VH/V(H)H display library. VH/V(H)H from E. coli transfected with four selected
      phage clones inhibited RdRp activity when tested by ELISA inhibition using 3'di
      cytidylate 25 nucleotide directed in vitro RNA synthesis. Deduced amino acid
      sequences of two clones showed V(H)H hallmark and were designated V(H)H6 and
      V(H)H24; other clones were conventional VH, designated VH9 and VH13. All VH/V(H)H
      were linked molecularly to a cell penetrating peptide, penetratin. The cell
      penetrable VH9, VH13, V(H)H6 and V(H)H24 added to culture of Huh7 cells
      transfected with JHF-1 RNA of genotype 2a HCV reduced the amounts of RNA
      intracellularly and in culture medium implying that they inhibited the virus
      replication. VH/V(H)H mimotopes matched with residues scattered on the polymerase
      fingers, palm and thumb which were likely juxtaposed to form conformational
      epitopes. Molecular docking revealed that the antibodies covered the RdRp
      catalytic groove. The transbodies await further studies for in vivo role in
      inhibiting HCV replication.

PMID- 23145136
TI  - Natural variation in seed very long chain fatty acid content is controlled by a
      new isoform of KCS18 in Arabidopsis thaliana.
AB  - Oil from oleaginous seeds is mainly composed of triacylglycerols. Very long chain
      fatty acids (VLCFAs) are major constituents of triacylglycerols in many seed oils
      and represent valuable feedstock for industrial purposes. To identify genetic
      factors governing natural variability in VLCFA biosynthesis, a quantitative trait
      loci (QTL) analysis using a recombinant inbred line population derived from a
      cross between accessions Bay-0 and Shahdara was performed in Arabidopsis
      thaliana. Two fatty acid chain length ratio (CLR) QTL were identified, with one
      major locus, CLR.2, accounting for 77% of the observed phenotypic variation. A
      fine mapping and candidate gene approach showed that a key enzyme of the fatty
      acid elongation pathway, the beta-ketoacyl-CoA synthase 18 (KCS18), was
      responsible for the CLR.2 QTL detected between Bay-0 and Shahdara. Association
      genetics and heterologous expression in yeast cells identified a single point
      mutation associated with an alteration of KCS18 activity, uncovering the
      molecular bases for the modulation of VLCFA content in these two natural
      populations of Arabidopsis. Identification of this kcs18 mutant with altered
      activity opens new perspectives for the modulation of oil composition in crop
      plants.

PMID- 23145137
TI  - Nocturnal homing: learning walks in a wandering spider?
AB  - Homing by the nocturnal Namib Desert spider Leucorchestris arenicola (Araneae:
      Sparassidae) is comparable to homing in diurnal bees, wasps and ants in terms of
      path length and layout. The spiders' homing is based on vision but their basic
      navigational strategy is unclear. Diurnal homing insects use memorised views of
      their home in snapshot matching strategies. The insects learn the visual scenery
      identifying their nest location during learning flights (e.g. bees and wasps) or
      walks (ants). These learning flights and walks are stereotyped movement patterns
      clearly different from other movement behaviours. If the visual homing of L.
      arenicola is also based on an image matching strategy they are likely to exhibit
      learning walks similar to diurnal insects. To explore this possibility we
      recorded departures of spiders from a new burrow in an unfamiliar area with
      infrared cameras and analysed their paths using computer tracking techniques. We
      found that L. arenicola performs distinct stereotyped movement patterns during
      the first part of their departures in an unfamiliar area and that they seem to
      learn the appearance of their home during these movement patterns. We conclude
      that the spiders perform learning walks and this strongly suggests that L.
      arenicola uses a visual memory of the burrow location when homing.

PMID- 23145138
TI  - fNIRS exhibits weak tuning to hand movement direction.
AB  - Functional near-infrared spectroscopy (fNIRS) has become an established tool to
      investigate brain function and is, due to its portability and resistance to
      electromagnetic noise, an interesting modality for brain-machine interfaces
      (BMIs). BMIs have been successfully realized using the decoding of movement
      kinematics from intra-cortical recordings in monkey and human. Recently, it has
      been shown that hemodynamic brain responses as measured by fMRI are modulated by
      the direction of hand movements. However, quantitative data on the decoding of
      movement direction from hemodynamic responses is still lacking and it remains
      unclear whether this can be achieved with fNIRS, which records signals at a lower
      spatial resolution but with the advantage of being portable. Here, we recorded
      brain activity with fNIRS above different cortical areas while subjects performed
      hand movements in two different directions. We found that hemodynamic signals in
      contralateral sensorimotor areas vary with the direction of movements, though
      only weakly. Using these signals, movement direction could be inferred on a
      single-trial basis with an accuracy of ~65% on average across subjects. The
      temporal evolution of decoding accuracy resembled that of typical hemodynamic
      responses observed in motor experiments. Simultaneous recordings with a head
      tracking system showed that head movements, at least up to some extent, do not
      influence the decoding of fNIRS signals. Due to the low accuracy, fNIRS is not a
      viable alternative for BMIs utilizing decoding of movement direction. However,
      due to its relative resistance to head movements, it is promising for studies
      investigating brain activity during motor experiments.

PMID- 23145139
TI  - Reduced germination of Orobanche cumana seeds in the presence of Arbuscular
      Mycorrhizal fungi or their exudates.
AB  - Broomrapes (Orobanche and Phelipanche spp) are parasitic plants responsible for
      important crop losses, and efficient procedures to control these pests are
      scarce. Biological control is one of the possible strategies to tackle these
      pests. Arbuscular Mycorrhizal (AM) fungi are widespread soil microorganisms that
      live symbiotically with the roots of most plant species, and they have already
      been tested on sorghum for their ability to reduce infestation by witchweeds,
      another kind of parasitic plants. In this work AM fungi were evaluated as
      potential biocontrol agents against Orobanche cumana, a broomrape species that
      specifically attacks sunflower. When inoculated simultaneously with O. cumana
      seeds, AM fungi could offer a moderate level of protection against the broomrape.
      Interestingly, this protection did not only rely on a reduced production of
      parasitic seed germination stimulants, as was proposed in previous studies.
      Rather, mycorrhizal root exudates had a negative impact on the germination of O.
      cumana induced by germination stimulants. A similar effect could be obtained with
      AM spore exudates, establishing the fungal origin of at least part of the active
      compounds. Together, our results demonstrate that AM fungi themselves can lead to
      a reduced rate of parasitic seed germination, in addition to possible effects
      mediated by the mycorrhizal plant. Combined with the other benefits of AM
      symbiosis, these effects make AM fungi an attractive option for biological
      control of O. cumana.

PMID- 23145140
TI  - Enhanced antitumor efficacy and reduced systemic toxicity of sulfatide-containing
      nanoliposomal doxorubicin in a xenograft model of colorectal cancer.
AB  - Sulfatide is a glycosphingolipid known to interact with several extracellular
      matrix proteins, such as tenascin-C which is overexpressed in many types of
      cancer including that of the colon. In view of the limited success of
      chemotherapy in colorectal cancer and high toxicity of doxorubicin (DOX), a
      sulfatide-containing liposome (SCL) encapsulation approach was taken to overcome
      these barriers. This study assessed the in vitro cytotoxicity, biodistribution,
      therapeutic efficacy and systemic toxicity in vivo of sulfatide-containing
      liposomal doxorubicin (SCL-DOX) using human colonic adenocarcinoma HT-29
      xenograft as the experimental model. In vitro, SCL-DOX was shown to be delivered
      into the nuclei and displayed prolonged retention compared with the free DOX. The
      use of this nanodrug delivery system to deliver DOX for treatment of tumor
      bearing mice produced a much improved therapeutic efficacy in terms of tumor
      growth suppression and extended survival in contrast to the free drug.
      Furthermore, treatment of tumor-bearing mice with SCL-DOX resulted in a lower DOX
      uptake in the principal sites of toxicity of the free drug, namely the heart and
      skin, as well as reduced myelosuppression and diminished cardiotoxicity. Such
      natural lipid-guided nanodrug delivery systems may represent a new strategy for
      the development of effective anticancer chemotherapeutics targeting the tumor
      microenvironment for both primary tumor and micrometastases.

PMID- 23145141
TI  - Role of alpha-actinin-3 in contractile properties of human single muscle fibers:
      a case series study in paraplegics.
AB  - A common nonsense polymorphism in the ACTN3 gene results in the absence of alpha
      actinin-3 in XX individuals. The wild type allele has been associated with power
      athlete status and an increased force output in numeral studies, though the
      mechanisms by which these effects occur are unclear. Recent findings in the
      Actn3(-/-) (KO) mouse suggest a shift towards 'slow' metabolic and contractile
      characteristics of fast muscle fibers lacking alpha-actinin-3. Skinned single
      fibers from the quadriceps muscle of three men with spinal cord injury (SCI) were
      tested regarding peak force, unloaded shortening velocity, force-velocity
      relationship, passive tension and calcium sensitivity. The SCI condition induces
      an 'equal environment condition' what makes these subjects ideal to study the
      role of alpha-actinin-3 on fiber type expression and single muscle fiber
      contractile properties. Genotyping for ACTN3 revealed that the three subjects
      were XX, RX and RR carriers, respectively. The XX carrier's biopsy was the only
      one that presented type I fibers with a complete lack of type II(x) fibers.
      Properties of hybrid type II(a)/II(x) fibers were compared between the three
      subjects. Absence of alpha-actinin-3 resulted in less stiff type II(a)/II(x)
      fibers. The heterozygote (RX) exhibited the highest fiber diameter (0.121+/-0.005
      mm) and CSA (0.012+/-0.001 mm(2)) and, as a consequence, the highest peak force
      (2.11+/-0.14 mN). Normalized peak force was similar in all three subjects (P =
      0.75). Unloaded shortening velocity was highest in R-allele carriers (P<0.001).
      No difference was found in calcium sensitivity. The preservation of type I fibers
      and the absence of type II(x) fibers in the XX individual indicate a restricted
      transformation of the muscle fiber composition to type II fibers in response to
      long-term muscle disuse. Lack of alpha-actinin-3 may decrease unloaded shortening
      velocity and increase fiber elasticity.

PMID- 23145142
TI  - SUMOylation of GTF2IRD1 regulates protein partner interactions and ubiquitin
      mediated degradation.
AB  - GTF2IRD1 is one of the genes implicated in Williams-Beuren syndrome, a disease
      caused by haploinsufficiency of certain dosage-sensitive genes within a
      hemizygous microdeletion of chromosome 7. GTF2IRD1 is a prime candidate for some
      of the major features of the disease, presumably caused by abnormally reduced
      abundance of this putative transcriptional repressor protein. GTF2IRD1 has been
      shown to interact with the E3 SUMO ligase PIASxbeta, but the significance of this
      relationship is largely unexplored. Here, we demonstrate that GTF2IRD1 can be
      SUMOylated by the SUMO E2 ligase UBC9 and the level of SUMOylation is enhanced by
      PIASxbeta. A major SUMOylation site was mapped to lysine 495 within a conserved
      SUMO consensus motif. SUMOylation of GTF2IRD1 alters the affinity of the protein
      for binding partners that contain SUMO-interacting motifs, including a novel
      family member of the HDAC repressor complex, ZMYM5, and PIASxbeta itself. In
      addition, we show that GTF2IRD1 is targeted for ubiquitination and proteasomal
      degradation. Cross regulation by SUMOylation modulates this process, thus
      potentially regulating the level of GTF2IRD1 protein in the cell. These findings,
      concerning post-translational control over the activity and stability of
      GTF2IRD1, together with previous work showing how GTF2IRD1 directly regulates its
      own transcription levels suggest an evolutionary requirement for fine control
      over GTF2IRD1 activity in the cell.

PMID- 23145143
TI  - No counterpart of visual perceptual echoes in the auditory system.
AB  - It has been previously demonstrated by our group that a visual stimulus made of
      dynamically changing luminance evokes an echo or reverberation at ~10 Hz, lasting
      up to a second. In this study we aimed to reveal whether similar echoes also
      exist in the auditory modality. A dynamically changing auditory stimulus
      equivalent to the visual stimulus was designed and employed in two separate
      series of experiments, and the presence of reverberations was analyzed based on
      reverse correlations between stimulus sequences and EEG epochs. The first
      experiment directly compared visual and auditory stimuli: while previous findings
      of ~10 Hz visual echoes were verified, no similar echo was found in the auditory
      modality regardless of frequency. In the second experiment, we tested if auditory
      sequences would influence the visual echoes when they were congruent or
      incongruent with the visual sequences. However, the results in that case
      similarly did not reveal any auditory echoes, nor any change in the
      characteristics of visual echoes as a function of audio-visual congruence. The
      negative findings from these experiments suggest that brain oscillations do not
      equivalently affect early sensory processes in the visual and auditory
      modalities, and that alpha (8-13 Hz) oscillations play a special role in vision.

PMID- 23145144
TI  - Role of PheE15 gate in ligand entry and nitric oxide detoxification function of
      mycobacterium tuberculosis truncated hemoglobin N.
AB  - The truncated hemoglobin N, HbN, of Mycobacterium tuberculosis is endowed with a
      potent nitric oxide dioxygenase (NOD) activity that allows it to relieve
      nitrosative stress and enhance in vivo survival of its host. Despite its small
      size, the protein matrix of HbN hosts a two-branched tunnel, consisting of
      orthogonal short and long channels, that connects the heme active site to the
      protein surface. A novel dual-path mechanism has been suggested to drive
      migration of O(2) and NO to the distal heme cavity. While oxygen migrates mainly
      by the short path, a ligand-induced conformational change regulates opening of
      the long tunnel branch for NO, via a phenylalanine (PheE15) residue that acts as
      a gate. Site-directed mutagenesis and molecular simulations have been used to
      examine the gating role played by PheE15 in modulating the NOD function of HbN.
      Mutants carrying replacement of PheE15 with alanine, isoleucine, tyrosine and
      tryptophan have similar O(2)/CO association kinetics, but display significant
      reduction in their NOD function. Molecular simulations substantiated that
      mutation at the PheE15 gate confers significant changes in the long tunnel, and
      therefore may affect the migration of ligands. These results support the pivotal
      role of PheE15 gate in modulating the diffusion of NO via the long tunnel branch
      in the oxygenated protein, and hence the NOD function of HbN.

PMID- 23145145
TI  - On the mechanism of synaptic depression induced by CaMKIIN, an endogenous
      inhibitor of CaMKII.
AB  - Activity-dependent synaptic plasticity underlies, at least in part, learning and
      memory processes. NMDA receptor (NMDAR)-dependent long-term potentiation (LTP) is
      a major synaptic plasticity model. During LTP induction, Ca(2+)/calmodulin
      dependent protein kinase II (CaMKII) is activated, autophosphorylated and
      persistently translocated to the postsynaptic density, where it binds to the
      NMDAR. If any of these steps is inhibited, LTP is disrupted. The endogenous
      CaMKII inhibitor proteins CaMKIINalpha,beta are rapidly upregulated in specific
      brain regions after learning. We recently showed that transient application of
      peptides derived from CaMKIINalpha (CN peptides) persistently depresses synaptic
      strength and reverses LTP saturation, as it allows further LTP induction in
      previously saturated pathways. The treatment disrupts basal CaMKII-NMDAR
      interaction and decreases bound CaMKII fraction in spines. To unravel CaMKIIN
      function and to further understand CaMKII role in synaptic strength maintenance,
      here we more deeply investigated the mechanism of synaptic depression induced by
      CN peptides (CN-depression) in rat hippocampal slices. We showed that CN
      depression does not require glutamatergic synaptic activity or Ca(2+) signaling,
      thus discarding unspecific triggering of activity-dependent long-term depression
      (LTD) in slices. Moreover, occlusion experiments revealed that CN-depression and
      NMDAR-LTD have different expression mechanisms. We showed that CN-depression does
      not involve complex metabolic pathways including protein synthesis or proteasome
      mediated degradation. Remarkably, CN-depression cannot be resolved in neonate
      rats, for which CaMKII is mostly cytosolic and virtually absent at the
      postsynaptic densities. Overall, our results support a direct effect of CN
      peptides on synaptic CaMKII-NMDAR binding and suggest that CaMKIINalpha,beta
      could be critical plasticity-related proteins that may operate as cell-wide
      homeostatic regulators preventing saturation of LTP mechanisms or may selectively
      erase LTP-induced traces in specific groups of synapses.

PMID- 23145146
TI  - Identification of sumoylation sites in CCDC6, the first identified RET partner
      gene in papillary thyroid carcinoma, uncovers a mode of regulating CCDC6 function
      on CREB1 transcriptional activity.
AB  - CCDC6 was originally identified in chimeric genes as caused by chromosomal
      translocation involving the RET protooncogene in some thyroid tumors. Recognised
      as a 65 kDa pro-apoptotic phosphoprotein, CCDC6 has been enrolled as an ATM
      substrate that contribute to protect genome integrity by modulating PP4c activity
      in response to genotoxic stress. Recently, CCDC6 has been identified as a
      repressor of CREB1-dependent transcription. Sumoylation has emerged as an
      important mechanism in transcriptional control. Here, we report the
      identification and characterization of three sites of sumoylation in CCDC6 (K74,
      K266 and K424) which are highly conserved in vertebrates. We demonstrate that the
      post-translational modifications by SUMO2 constrain most of the CCDC6 protein in
      the cytosol and affect its functional interaction with CREB1 with a decrease of
      CCDC6 repressive function on CREB1 transcriptional activity. Indeed, the
      impairment of functional outcome of sumoylated CCDC6 is obtained knocking down
      all three the sumoylation sites. Interestingly, in thyroid cells the SUMO2
      mediated CCDC6 post-translational modifications are induced by Forskolin, a cAMP
      analog. Signal transduction via the cAMP pathway is known to be ubiquitous and
      represents a major line of communication between many organisms and their
      environment. We believe that CCDC6 could be an important player in the dynamics
      of cAMP signaling by fine regulating CREB1 transcriptional activity in normal and
      transformed thyroid cells.

PMID- 23145147
TI  - A "spike-based" grammar underlies directional modification in network
      connectivity: effect on bursting activity and implications for bio-hybrids
      systems.
AB  - Developed biological systems are endowed with the ability of interacting with the
      environment; they sense the external state and react to it by changing their own
      internal state. Many attempts have been made to build 'hybrids' with the ability
      of perceiving, modifying and reacting to external modifications. Investigation of
      the rules that govern network changes in a hybrid system may lead to finding
      effective methods for 'programming' the neural tissue toward a desired task. Here
      we show a new perspective in the use of cortical neuronal cultures from embryonic
      mouse as a working platform to study targeted synaptic modifications. Differently
      from the common timing-based methods applied in bio-hybrids robotics, here we
      evaluated the importance of endogenous spike timing in the information
      processing. We characterized the influence of a spike-patterned stimulus in
      determining changes in neuronal synchronization (connectivity strength and
      precision) of the evoked spiking and bursting activity in the network. We show
      that tailoring the stimulation pattern upon a neuronal spike timing induces the
      network to respond stronger and more precisely to the stimulation. Interestingly,
      the induced modifications are conveyed more consistently in the burst timing.
      This increase in strength and precision may be a key in the interaction of the
      network with the external world and may be used to induce directional changes in
      bio-hybrid systems.

PMID- 23145148
TI  - Hyperactivation of PARP triggers nonhomologous end-joining in repair-deficient
      mouse fibroblasts.
AB  - Regulation of poly(ADP-ribose) (PAR) synthesis and turnover is critical to
      determining cell fate after genotoxic stress. Hyperactivation of PAR synthesis by
      poly(ADP-ribose) polymerase-1 (PARP-1) occurs when cells deficient in DNA repair
      are exposed to genotoxic agents; however, the function of this hyperactivation
      has not been adequately explained. Here, we examine PAR synthesis in mouse
      fibroblasts deficient in the base excision repair enzyme DNA polymerase beta (pol
      beta). The extent and duration of PARP-1 activation was measured after exposure
      to either the DNA alkylating agent, methyl methanesulfonate (MMS), or to low
      energy laser-induced DNA damage. There was strong DNA damage-induced
      hyperactivation of PARP-1 in pol beta nullcells, but not in wild-type cells. In
      the case of MMS treatment, PAR synthesis did not lead to cell death in the pol
      beta null cells, but instead resulted in increased PARylation of the
      nonhomologous end-joining (NHEJ) protein Ku70 and increased association of Ku70
      with PARP-1. Inhibition of the NHEJ factor DNA-PK, under conditions of MMS
      induced PARP-1 hyperactivation, enhanced necrotic cell death. These data suggest
      that PARP-1 hyperactivation is a protective mechanism triggering the classical
      NHEJ DNA repair pathway when the primary alkylated base damage repair pathway is
      compromised.

PMID- 23145149
TI  - siRNA has greatly elevated mismatch tolerance at 3'-UTR sites.
AB  - It has been noted that target sites located in the coding region or the 3'
      untranslated region (3'-UTR) can be silenced to significantly different levels by
      the same siRNA, but little is known about at what specificity the silencing was
      achieved. In an exploration of positional effects on siRNA specificity by
      luciferase reporter system, we surprisingly discovered that siRNA had greatly
      elevated tolerance towards mismatches in target sites in the 3'-UTR of the mRNA
      compared with the same target sites cloned in the coding region. Assessment of
      changes in protein and mRNA levels suggested that the differential mismatch
      tolerance might have resulted from location-specific translational repression in
      the 3'-UTR. Ablation of argonaute proteins by AGO-specific siRNAs revealed that
      the AGO2 had major impact on siRNA silencing activity against sites in both
      coding region and 3'-UTR, while the silencing of nonnucleolytic AGO proteins
      (AGO1, AGO3 and AGO4) did not significantly affect silencing of sites in either
      region. This paper revealed the discovery that the specificity of an siRNA can be
      affected by the location of its target site.

PMID- 23145150
TI  - Hepatitis B virus infection in HIV-positive individuals in the UK collaborative
      HIV cohort (UK CHIC) study.
AB  - BACKGROUND: Hepatitis B virus (HBV) infection is an increasingly important cause
      of morbidity and mortality in HIV-infected adults. This study aimed to determine
      the prevalence and incidence of HBV in the UK CHIC Study, a multicentre
      observational cohort. METHODS AND FINDINGS: 12 HIV treatment centres were
      included. Of 37,331 patients, 27,450 had at least one test (HBsAg, anti-HBs or
      anti-HBc) result post-1996 available. 16,043 were white, 8,130 black and 3,277
      other ethnicity. Route of exposure was homosexual sex 15,223 males, heterosexual
      sex 3,258 males and 5,384 females, injecting drug use 862 and other 2,723. The
      main outcome measures used were the cumulative prevalence and the incidence of
      HBV coinfection. HBV susceptible patients were followed up until HBsAg and/or
      anti-HBc seroconversion incident infection, evidence of vaccination or last
      visit. Poisson regression was used to determine associated factors. 25,973 had at
      least one HBsAg test result. Participants with HBsAg results were typically MSM
      (57%) and white (59%) (similar to the cohort as a whole). The cumulative
      prevalence of detectable HBsAg was 6.9% (6.6 to 7.2%). Among the 3,379 initially
      HBV-susceptible patients, the incidence of HBV infection was 1.7 (1.5 to 1.9)/100
      person-years. Factors associated with incident infection were older age and IDU.
      The main limitation of the study was that 30% of participants did not have any
      HBsAg results available. However baseline characteristics of those with results
      did not differ from those of the whole cohort. Efforts are on-going to improve
      data collection. CONCLUSIONS: The prevalence of HBV in UK CHIC is in line with
      estimates from other studies and low by international standards. Incident
      infection continued to occur even after entry to the cohort, emphasising the need
      to ensure early vaccination.

PMID- 23145151
TI  - Left-handedness in professional and amateur tennis.
AB  - Negative frequency-dependent effects rather than innate predispositions may
      provide left-handers with an advantage in one-on-one fighting situations. Support
      mainly comes from cross-sectional studies which found significantly enhanced left
      hander frequencies among elite athletes exclusively in interactive sports such as
      baseball, cricket, fencing and tennis. Since professional athletes' training
      regimes continuously improve, however, an important unsolved question is whether
      the left-handers' advantage in individual sports like tennis persists over time.
      To this end, we longitudinally tracked left-hander frequencies in year-end world
      rankings (men: 1973-2011, ladies: 1975-2011) and at Grand Slam tournaments (1968
      2011) in male and female tennis professionals. Here we show that the positive
      impact of left-handed performance on high achievement in elite tennis was
      moderate and decreased in male professionals over time and was almost absent in
      female professionals. For both sexes, left-hander frequencies among year-end top
      10 players linearly decreased over the period considered. Moreover, left
      handedness was, however, no longer seems associated with higher probability of
      attaining high year-end world ranking position in male professionals. In
      contrast, cross-sectional data on left-hander frequencies in male and female
      amateur players suggest that a left-handers' advantage may still occur on lower
      performance levels. Collectively, our data is in accordance with the frequency
      dependent hypothesis since reduced experience with left-handers in tennis is
      likely to be compensated by players' professionalism.

PMID- 23145152
TI  - Bioinformatic analysis of epigenetic and microRNA mediated regulation of drought
      responsive genes in rice.
AB  - Drought stress response is a complex trait regulated at multiple levels. Changes
      in the epigenetic and miRNA regulatory landscape can dramatically alter the
      outcome of a stress response. However, little is known about the scope and extent
      of these regulatory factors on drought related cellular processes and functions.
      To this end, we selected a list of 5468 drought responsive genes (DRGs) of rice
      identified in multiple microarray studies and mapped the DNA methylation regions
      found in a genome wide methylcytosine immunoprecipitation and sequencing (mCIP
      Seq) study to their genic and promoter regions, identified the chromatin
      remodeling genes and the genes that are targets of miRNAs. We found statistically
      significant enrichment of DNA methylation reads and miRNA target sequences in
      DRGs compared to a random set of genes. About 75% of the DRGs annotated to be
      involved in chromatin remodeling were downregulated. We found one-third of the
      DRGs are targeted by two-thirds of all known/predicted miRNAs in rice which
      include many transcription factors targeted by more than five miRNAs. Clustering
      analysis of the DRGs with epigenetic and miRNA features revealed, upregulated
      cluster was enriched in drought tolerance mechanisms while the downregulated
      cluster was enriched in drought resistance mechanisms evident by their unique
      gene ontologies (GOs), protein-protein interactions (PPIs), specific
      transcription factors, protein domains and metabolic pathways. Further, we
      analyzed the proteome of two weeks old young rice plants treated with a global
      demethylating agent, 5-azacytidine (5-azaC), subjected to drought stress and
      identified 56 protein spots that are differentially expressed. Out of the 56
      spots, 35 were differently expressed in the sample with both demethylation and
      drought stress treatments and 28 (50%) were part of DRGs considered in the
      bioinformatic analysis.

PMID- 23145153
TI  - CREST--classification resources for environmental sequence tags.
AB  - Sequencing of taxonomic or phylogenetic markers is becoming a fast and efficient
      method for studying environmental microbial communities. This has resulted in a
      steadily growing collection of marker sequences, most notably of the small
      subunit (SSU) ribosomal RNA gene, and an increased understanding of microbial
      phylogeny, diversity and community composition patterns. However, to utilize
      these large datasets together with new sequencing technologies, a reliable and
      flexible system for taxonomic classification is critical. We developed CREST
      (Classification Resources for Environmental Sequence Tags), a set of resources
      and tools for generating and utilizing custom taxonomies and reference datasets
      for classification of environmental sequences. CREST uses an alignment-based
      classification method with the lowest common ancestor algorithm. It also uses
      explicit rank similarity criteria to reduce false positives and identify novel
      taxa. We implemented this method in a web server, a command line tool and the
      graphical user interfaced program MEGAN. Further, we provide the SSU rRNA
      reference database and taxonomy SilvaMod, derived from the publicly available
      SILVA SSURef, for classification of sequences from bacteria, archaea and
      eukaryotes. Using cross-validation and environmental datasets, we compared the
      performance of CREST and SilvaMod to the RDP Classifier. We also utilized
      Greengenes as a reference database, both with CREST and the RDP Classifier. These
      analyses indicate that CREST performs better than alignment-free methods with
      higher recall rate (sensitivity) as well as precision, and with the ability to
      accurately identify most sequences from novel taxa. Classification using SilvaMod
      performed better than with Greengenes, particularly when applied to environmental
      sequences. CREST is freely available under a GNU General Public License (v3) from
      http://apps.cbu.uib.no/crest and http://lcaclassifier.googlecode.com.

PMID- 23145154
TI  - Structure and mechanics of supporting cells in the guinea pig organ of Corti.
AB  - The mechanical properties of the mammalian organ of Corti determine its
      sensitivity to sound frequency and intensity, and the structure of supporting
      cells changes progressively with frequency along the cochlea. From the apex (low
      frequency) to the base (high frequency) of the guinea pig cochlea inner pillar
      cells decrease in length incrementally from 75-55 um whilst the number of axial
      microtubules increases from 1,300-2,100. The respective values for outer pillar
      cells are 120-65 um and 1,500-3,000. This correlates with a progressive decrease
      in the length of the outer hair cells from >100 um to 20 um. Deiters'cell bodies
      vary from 60-50 um long with relatively little change in microtubule number.
      Their phalangeal processes reflect the lengths of outer hair cells but their
      microtubule numbers do not change systematically. Correlations between cell
      length, microtubule number and cochlear location are poor below 1 kHz. Cell
      stiffness was estimated from direct mechanical measurements made previously from
      isolated inner and outer pillar cells. We estimate that between 200 Hz and 20 kHz
      axial stiffness, bending stiffness and buckling limits increase, respectively,~3,
      6 and 4 fold for outer pillar cells, ~2, 3 and 2.5 fold for inner pillar cells
      and ~7, 20 and 24 fold for the phalangeal processes of Deiters'cells. There was
      little change in the Deiters'cell bodies for any parameter. Compensating for
      effective cell length the pillar cells are likely to be considerably stiffer than
      Deiters'cells with buckling limits 10-40 times greater. These data show a clear
      relationship between cell mechanics and frequency. However, measurements from
      single cells alone are insufficient and they must be combined with more accurate
      details of how the multicellular architecture influences the mechanical
      properties of the whole organ.

PMID- 23145156
TI  - A novel method for measuring the diffusion, partition and convective mass
      transfer coefficients of formaldehyde and VOC in building materials.
AB  - The diffusion coefficient (D(m)) and material/air partition coefficient (K) are
      two key parameters characterizing the formaldehyde and volatile organic compounds
      (VOC) sorption behavior in building materials. By virtue of the sorption process
      in airtight chamber, this paper proposes a novel method to measure the two key
      parameters, as well as the convective mass transfer coefficient (h(m)). Compared
      to traditional methods, it has the following merits: (1) the K, D(m) and h(m) can
      be simultaneously obtained, thus is convenient to use; (2) it is time-saving,
      just one sorption process in airtight chamber is required; (3) the determination
      of h(m) is based on the formaldehyde and VOC concentration data in the test
      chamber rather than the generally used empirical correlations obtained from the
      heat and mass transfer analogy, thus is more accurate and can be regarded as a
      significant improvement. The present method is applied to measure the three
      parameters by treating the experimental data in the literature, and good results
      are obtained, which validates the effectiveness of the method. Our new method
      also provides a potential pathway for measuring h(m) of semi-volatile organic
      compounds (SVOC) by using that of VOC.

PMID- 23145155
TI  - HERV-E-mediated modulation of PLA2G4A transcription in urothelial carcinoma.
AB  - Human endogenous retroviruses (HERV) and related elements account for more than
      8% of the human genome and significantly contribute to the human transcriptome by
      long terminal repeat (LTR) promoter activity. In this context, HERVs are thought
      to intervene in the expression of adjacent genes by providing regulatory
      sequences (cis-effect) or via noncoding RNA including natural antisense
      transcripts. To address the potential impact of HERV activity in urothelial
      carcinoma, we comparatively analyzed the HERV transcription profiles in paired
      samples of non-malignant urothelium and urothelial carcinoma derived from 13
      patients with bladder cancer by means of a retrovirus-specific microarray
      (RetroArray). We established a characteristic HERV signature consisting of six
      ubiquitously active HERV subgroups (E4-1, HERV-Rb, ERV9, HERV-K-T47D, NMWV3, HERV
      KC4). The transcription pattern is largely identical in human urothelial
      carcinoma, non-malignant urothelial tissue, four tumor-derived cell lines and in
      a non-malignant urothelial cell line (UROtsa). Quantitative reverse transcriptase
      PCR (qRT-PCR) of HERV-E4-1, HERV-K(HML-6) and HERV-T(S71-TK1) revealed a bias to
      lower HERV activity in carcinoma samples compared to non-malignant tissue.
      Determination of active HERV-E4-1 loci by cloning and sequencing revealed six
      HERV-E4-1 proviral loci that are differentially regulated in urothelial carcinoma
      cells and normal tissue. Two full-length HERV-E4-1 proviruses, HERV-Ec1 and HERV
      Ec6, are located in antisense orientation in introns of the genes PLA2G4A and
      RNGTT, respectively. PLA2G4A encodes a cytosolic phospholipase A2 (cPLA2) that is
      dysregulated in many human tumors. PLA2G4A and HERV-Ec1 displayed reciprocal
      transcript levels in 7 of 11 urothelial carcinoma patients. Moreover, reciprocal
      shifts were observed after treatment of UROtsa cells with HERV-Ec1 and PLA2G4A
      directed siRNAs or 5-aza-2'-deoxycytidine (aza-dC) pointing to an antagonistic
      regulation of PLA2G4A and HERV-Ec1 transcription in human urothelial cells. We
      suggest that transcription of HERV-Ec1 contributes to fine tuning of cPLA2
      expression, thereby facilitating tumorigenesis.

PMID- 23145157
TI  - Relationship between resting pulse rate and lipid metabolic dysfunctions in
      Chinese adults living in rural areas.
AB  - BACKGROUND: Resting pulse rate has been observed to be associated with
      cardiovascular diseases. However, its association with lipid metabolic
      dysfunctions remains unclear, especially resting pulse rate as an indicator for
      identifying the risk of lipid metabolic dysfunctions. The purpose of this study
      was to examine the association between resting pulse rate and lipid metabolic
      dysfunctions, and then evaluate the feasibility of resting pulse rate as an
      indicator for screening the risk of lipid metabolic dysfunctions. METHODS: A
      cross-sectional survey was performed, and 16,926 subjects were included in this
      study from rural community residents aged 35-78 years. Resting pulse rate and
      relevant covariates were collected from a standard questionnaire. The fasting
      blood samples were collected and measured for lipid profile. Predictive
      performance was analyzed by receiver operating characteristic (ROC) curve.
      RESULTS: A significant correlation was observed between resting pulse rate and TC
      (r = 0.102, P = 0.001), TG (r = 0.182, P = 0.001), and dyslipidemia (r = 0.037, P
      = 0.008). In the multivariate models, the adjusted odds ratios for
      hypercholesterolemia (from 1.07 to 1.15), hypertriglyceridemia (1.11 to 1.16),
      low HDL hypercholesterolemia (1.03 to 1.06), high LDL hypercholesterolemia (0.92
      to 1.14), and dyslipidemia (1.04 to 1.07) were positively increased across
      quartiles of resting pulse rate (P for trend <0.05). The ROC curve indicated that
      resting pulse rate had low sensitivity (78.95%, 74.18%, 51.54%, 44.39%, and
      54.22%), specificity (55.88%, 59.46%, 57.27%, 65.02%, and 60.56%), and the area
      under ROC curve (0.70, 0.69, 0.54, 0.56, and 0.58) for identifying the risk of
      hypercholesterolemia, hypertriglyceridemia, low HDL hypercholesterolemia, high
      LDL hypercholesterolemia, and dyslipidemia, respectively. CONCLUSION: Fast
      resting pulse rate was associated with a moderate increased risk of lipid
      metabolic dysfunctions in rural adults. However, resting pulse rate as an
      indicator has limited potential for screening the risk of lipid metabolic
      dysfunctions.

PMID- 23145158
TI  - Cane toads on cowpats: commercial livestock production facilitates toad invasion
      in tropical australia.
AB  - Habitat disturbance and the spread of invasive organisms are major threats to
      biodiversity, but the interactions between these two factors remain poorly
      understood in many systems. Grazing activities may facilitate the spread of
      invasive cane toads (Rhinella marina) through tropical Australia by providing
      year-round access to otherwise-seasonal resources. We quantified the cane toad's
      use of cowpats (feces piles) in the field, and conducted experimental trials to
      assess the potential role of cowpats as sources of prey, water, and warmth for
      toads. Our field surveys show that cane toads are found on or near cowpats more
      often than expected by chance. Field-enclosure experiments show that cowpats
      facilitate toad feeding by providing access to dung beetles. Cowpats also offer
      moist surfaces that can reduce dehydration rates of toads and are warmer than
      other nearby substrates. Livestock grazing is the primary form of land use over
      vast areas of Australia, and pastoral activities may have contributed
      substantially to the cane toad's successful invasion of that continent.

PMID- 23145159
TI  - Interaction of sleep and emotional content on the production of false memories.
AB  - Sleep benefits veridical memories, resulting in superior recall relative to off
      line intervals spent awake. Sleep also increases false memory recall in the Deese
      Roediger-McDermott (DRM) paradigm. Given the suggestion that emotional veridical
      memories are prioritized for consolidation over sleep, here we examined whether
      emotion modulates sleep's effect on false memory formation. Participants listened
      to semantically related word lists lacking a critical lure representing each
      list's "gist." Free recall was tested after 12 hours containing sleep or wake.
      The Sleep group recalled more studied words than the Wake group but only for
      emotionally neutral lists. False memories of both negative and neutral critical
      lures were greater following sleep relative to wake. Morning and Evening control
      groups (20-minute delay) did not differ ruling out circadian accounts for these
      differences. These results support the adaptive function of sleep in both
      promoting the consolidation of veridical declarative memories and in extracting
      unifying aspects from memory details.

PMID- 23145160
TI  - Conquered from the deep sea? A new deep-sea isopod species from the Antarctic
      shelf shows pattern of recent colonization.
AB  - The Amundsen Sea, Antarctica, is amongst the most rapidly changing environments
      of the world. Its benthic inhabitants are barely known and the BIOPEARL 2 project
      was one of the first to biologically explore this region. Collected during this
      expedition, Macrostylis roaldi sp. nov. is described as the first isopod
      discovered on the Amundsen-Sea shelf. Amongst many characteristic features, the
      most obvious characters unique for M. roaldi are the rather short pleotelson and
      short operculum as well as the trapezoid shape of the pleotelson in adult males.
      We used DNA barcodes (COI) and additional mitochondrial markers (12S, 16S) to
      reciprocally illuminate morphological results and nucleotide variability. In
      contrast to many other deep-sea isopods, this species is common and shows a wide
      distribution. Its range spreads from Pine Island Bay at inner shelf right to the
      shelf break and across 1,000 m bathymetrically. Its gene pool is homogenized
      across space and depth. This is indicative for a genetic bottleneck or a recent
      colonization history. Our results suggest further that migratory or dispersal
      capabilities of some species of brooding macrobenthos have been underestimated.
      This might be relevant for the species' potential to cope with effects of climate
      change. To determine where this species could have survived the last glacial
      period, alternative refuge possibilities are discussed.

PMID- 23145161
TI  - Prevalence of anti-tuberculosis drug resistance in foreign-born tuberculosis
      cases in the U.S. and in their countries of origin.
AB  - BACKGROUND: Foreign-born individuals comprise >50% of tuberculosis (TB) cases in
      the U.S. Since anti-TB drug resistance is more common in most other countries,
      when evaluating a foreign-born individual for TB, one must consider the risk of
      drug resistance. Naturally, clinicians query The Global Project on Anti
      tuberculosis Drug Resistance Surveillance (Global DRS) which provides population
      based data on the prevalence of anti-TB drug resistance in 127 countries starting
      in 1994. However, foreign-born persons in the U.S. are a biased sample of the
      population of their countries of origin, and Global DRS data may not accurately
      predict their risk of drug resistance. Since implementing drug resistance
      surveillance in 1993, the U.S. National TB Surveillance System (NTSS) has
      accumulated systematic data on over 130,000 foreign-born TB cases from more than
      200 countries and territories. Our objective was to determine whether the
      prevalence of drug resistance among foreign-born TB cases correlates better with
      data from the Global DRS or with data on foreign-born TB cases in the NTSS.
      METHODS AND FINDINGS: We compared the prevalence of resistance to isoniazid and
      rifampin among foreign-born TB cases in the U.S., 2007-2009, with US NTSS data
      from 1993 to 2006 and with Global DRS data from 1994-2007 visually with
      scatterplots and statistically with correlation and linear regression analyses.
      Among foreign-born TB cases in the U.S., 2007-2009, the prevalence of isoniazid
      resistance and multidrug resistance (MDR, i.e. resistance to isoniazid and
      rifampin), correlated much better with 1993-2006 US surveillance data (isoniazid:
      r = 0.95, P<.001, MDR: r = 0.75, P<.001) than with Global DRS data, 1994-2007
      (isoniazid: r = 0.55, P = .001; MDR: r = 0.50, P<.001). CONCLUSION: Since 1993,
      the US NTSS has accumulated sufficient data on foreign-born TB cases to estimate
      the risk of drug resistance among such individuals better than data from the
      Global DRS.

PMID- 23145162
TI  - Genetic variation in MDM2 and p14ARF and susceptibility to salivary gland
      carcinoma.
AB  - BACKGROUND: The p14(ARF)/MDM2/p53 pathway plays an important role in modulation
      of DNA damage and oxidative stress responses. The aim of this study was to
      determine whether genetic variants in MDM2 and p14(ARF) are associated with risk
      of salivary gland carcinoma (SGC). METHODS: Four single nucleotide polymorphisms
      (SNPs) in MDM2 and p14(ARF) (MDM2-rs2279744, MDM2-rs937283, p14(ARF)-rs3731217,
      and p14(ARF)-rs3088440) were genotyped in 156 patients with SGC and 511 cancer
      free controls. Multivariate logistic regression analysis was performed to
      calculate odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: MDM2
      rs2279744 was significantly associated with a moderately increased risk of SGC
      (OR, 1.5, 95% CI, 1.1-2.2). There was a trend toward significantly increased SGC
      risk with increasing number of risk genotypes of the four polymorphisms (P(trend)
      = 0.004). Individuals carrying 3-4 risk genotypes in MDM2 and p14(ARF) were at
      increased SGC risk (OR, 2.0, 95% CI, 1.1-2.7) compared with individuals carrying
      0-2 risk genotypes. Moreover, the combined effect of risk genotypes of MDM2 and
      p14(ARF) was more pronounced among young subjects (<= 45 years), female subjects,
      subjects with race/ethnicity other than non-Hispanic white, ever-smokers, and
      ever-drinkers. CONCLUSION: Our results support the involvement of SNPs of MDM2
      and p14(ARF), either alone or more likely in combination, in susceptibility to
      SGC. Larger studies are needed to validate our findings.

PMID- 23145163
TI  - Use of the comet-FISH assay to compare DNA damage and repair in p53 and hTERT
      genes following ionizing radiation.
AB  - The alkaline single cell gel electrophoresis (comet) assay can be combined with
      fluorescent in situ hybridisation (FISH) methodology in order to investigate the
      localisation of specific gene domains within an individual cell. The number and
      position of the fluorescent signal(s) provides information about the relative
      damage and subsequent repair that is occurring in the targeted gene domain(s). In
      this study, we have optimised the comet-FISH assay to detect and compare DNA
      damage and repair in the p53 and hTERT gene regions of bladder cancer cell-lines
      RT4 and RT112, normal fibroblasts and Cockayne Syndrome (CS) fibroblasts
      following gamma-radiation. Cells were exposed to 5Gy gamma-radiation and repair
      followed for up to 60 minutes. At each repair time-point, the number and location
      of p53 and hTERT hybridisation spots was recorded in addition to standard comet
      measurements. In bladder cancer cell-lines and normal fibroblasts, the p53 gene
      region was found to be rapidly repaired relative to the hTERT gene region and the
      overall genome, a phenomenon that appeared to be independent of hTERT
      transcriptional activity. However, in the CS fibroblasts, which are defective in
      transcription coupled repair (TCR), this rapid repair of the p53 gene region was
      not observed when compared to both the hTERT gene region and the overall genome,
      proving the assay can detect variations in DNA repair in the same gene. In
      conclusion, we propose that the comet-FISH assay is a sensitive and rapid method
      for detecting differences in DNA damage and repair between different gene regions
      in individual cells in response to radiation. We suggest this increases its
      potential for measuring radiosensitivity in cells and may therefore have value in
      a clinical setting.

PMID- 23145164
TI  - Lysosomotropic properties of weakly basic anticancer agents promote cancer cell
      selectivity in vitro.
AB  - Drug distribution in cells is a fundamentally important, yet often overlooked,
      variable in drug efficacy. Many weakly basic anticancer agents accumulate
      extensively in the acidic lysosomes of normal cells through ion trapping.
      Lysosomal trapping reduces the activity of anticancer drugs, since anticancer
      drug targets are often localized in the cell cytosol or nucleus. Some cancer
      cells have defective acidification of lysosomes, which causes a redistribution of
      trapped drugs from the lysosomes to the cytosol. We have previously established
      that such differences in drug localization between normal and cancer cells can
      contribute to the apparent selectivity of weakly basic drugs to cancer cells in
      vitro. In this work, we tested whether this intracellular distribution-based drug
      selectivity could be optimized based on the acid dissociation constant (pKa) of
      the drug, which is one of the determinants of lysosomal sequestration capacity.
      We synthesized seven weakly basic structural analogs of the Hsp90 inhibitor
      geldanamycin (GDA) with pKa values ranging from 5 to 12. The selectivity of each
      analog was expressed by taking ratios of anti-proliferative IC(50) values of the
      inhibitors in normal fibroblasts to the IC(50) values in human leukemic HL-60
      cells. Similar selectivity assessments were performed in a pair of cancer cell
      lines that differed in lysosomal pH as a result of siRNA-mediated alteration of
      vacuolar proton ATPase subunit expression. Optimal selectivity was observed for
      analogs with pKa values near 8. Similar trends were observed with commercial
      anticancer agents with varying weakly basic pKa values. These evaluations advance
      our understanding of how weakly basic properties can be optimized to achieve
      maximum anticancer drug selectivity towards cancer cells with defective lysosomal
      acidification in vitro. Additional in vivo studies are needed to examine the
      utility of this approach for enhancing selectivity.

PMID- 23145165
TI  - Paradoxical relationship between Mn superoxide dismutase deficiency and radiation
      induced cognitive defects.
AB  - Radiation therapy of the CNS, even at low doses, can lead to deficits in
      neurocognitive functions. Reduction in hippocampal neurogenesis is usually, but
      not always, associated with cognitive deficits resulting from radiation therapy.
      Generation of reactive oxygen species is considered the main cause of radiation
      induced tissue injuries, and elevated levels of oxidative stress persist long
      after the initial cranial irradiation. Consequently, mutant mice with reduced
      levels of the mitochondrial antioxidant enzyme, Mn superoxide dismutase (MnSOD or
      Sod2), are expected to be more sensitive to radiation-induced changes in
      hippocampal neurogenesis and the related functions. In this study, we showed that
      MnSOD deficiency led to reduced generation of immature neurons in Sod2-/+ mice
      even though progenitor cell proliferation was not affected. Compared to
      irradiated Sod2+/+ mice, which showed cognitive defects and reduced
      differentiation of newborn cells towards the neuronal lineage, irradiated Sod2-/+
      mice showed normal hippocampal-dependent cognitive functions and normal
      differentiation pattern for newborn neurons and astroglia. However, we also
      observed a disproportional decrease in newborn neurons in irradiated Sod2-/+
      following behavioral studies, suggesting that MnSOD deficiency may render newborn
      neurons more sensitive to stress from behavioral trainings following cranial
      irradiation. A positive correlation between normal cognitive functions and normal
      dendritic spine densities in dentate granule cells was observed. The data suggest
      that maintenance of synaptic connections, via maintenance of dendritic spines,
      may be important for normal cognitive functions following cranial irradiation.

PMID- 23145166
TI  - Sensory attenuation of self-produced feedback: the Lombard effect revisited.
AB  - The Lombard effect describes the automatic and involuntary increase in vocal
      intensity that speakers exhibit in a noisy environment. Previous studies of the
      Lombard effect have typically focused on the relationship between speaking and
      hearing. Automatic and involuntary increases in motor output have also been noted
      in studies of finger force production, an effect attributed to mechanisms of
      sensory attenuation. The present study tested the hypothesis that sensory
      attenuation mechanisms also underlie expression of the Lombard effect.
      Participants vocalized phonemes in time with a metronome, while auditory and
      visual feedback of their performance were manipulated or removed during the
      course of the trial. We demonstrate that providing a visual reference to
      calibrate somatosensory-based judgments of current vocal intensity resulted in
      reduced expression of the Lombard effect. Our results suggest that sensory
      attenuation effects typically seen in fingertip force production play an
      important role in the control of speech volume.

PMID- 23145167
TI  - Modeling amyloid-beta as homogeneous dodecamers and in complex with cellular
      prion protein.
AB  - Soluble amyloid beta (Abeta) peptide has been linked to the pathology of
      Alzheimer's disease. A variety of soluble oligomers have been observed to be
      toxic, ranging from dimers to protofibrils. No tertiary structure has been
      identified as a single biologically relevant form, though many models are
      comprised of highly ordered beta-sheets. Evidence exists for much less ordered
      toxic oligomers. The mechanism of toxicity remains highly debated and probably
      involves multiple pathways. Interaction of Abeta oligomers with the N-terminus of
      the cellular form of the prion protein (PrP(c)) has recently been proposed. The
      intrinsically disordered nature of this protein and the highly polymorphic nature
      of Abeta oligomers make structural resolution of the complex exceptionally
      challenging. In this study, molecular dynamics simulations are performed for
      dodecameric assemblies of Abeta comprised of monomers having a single, short
      antiparallel beta-hairpin at the C-terminus. The resulting models, devoid of any
      intermolecular hydrogen bonds, are shown to correlate well with experimental data
      and are found to be quite stable within the hydrophobic core, whereas the alpha
      helical N-termini transform to a random coil state. This indicates that highly
      ordered assemblies are not required for stability and less ordered oligomers are
      a viable component in the population of soluble oligomers. In addition, a
      tentative model is proposed for the association of Abeta dimers with a double
      deletion mutant of the intrinsically disordered N-terminus of PrP(c). This may be
      useful as a conceptual working model for the binding of higher order oligomers
      and in the design of further experiments.

PMID- 23145168
TI  - Do seabirds differ from other migrants in their travel arrangements? On route
      strategies of Cory's shearwater during its trans-equatorial journey.
AB  - Long-distance migrants have developed diverse strategies to deal with the
      challenges imposed by their annual journeys. These are relatively well studied in
      some avian groups, such as passerines, shorebirds and raptors. In contrast, few
      studies have addressed the migratory behaviour of pelagic birds in the light of
      current theories of optimal migration. Using a dataset of 100 complete migratory
      tracks gathered along four years, we performed a detailed study on the migratory
      strategy of a pelagic trans-equatorial migrant, the Cory's shearwater Calonectris
      diomedea. We analysed daily routines, stopover ecology and travel speed, as well
      as the influence of the moon on several behavioural patterns. Cory's shearwaters
      adopted a "fly-and-forage" strategy when migrating, similarly to what has been
      observed in some raptors. However, by flying by dynamic soaring, shearwaters
      attained high overall migration speeds, and were able to travel thousands of
      kilometres without making major stopovers and, apparently, without a noticeable
      pre-migratory fattening period. Other major findings of this study include the
      ability to adapt daily schedules when crossing major ecological barriers, and the
      constant adjustment of migration speed implying higher rates of travel in the pre
      breeding movement, with a final sprint to the nesting colony. The present study
      also highlights a preference of Cory's shearwaters for starting travel at
      twilight and documents a strong relationship between their migratory activity and
      the moon phase.

PMID- 23145169
TI  - Negative regulation of hepatitis C virus specific immunity is highly
      heterogeneous and modulated by pegylated interferon-alpha/ribavirin therapy.
AB  - Specific inhibitory mechanisms suppress the T-cell response against the hepatitis
      C virus (HCV) in chronically infected patients. However, the relative importance
      of suppression by IL-10, TGF-beta and regulatory T-cells and the impact of
      pegylated interferon-alpha and ribavirin (PegIFN-alpha/ribavirin) therapy on
      these inhibitory mechanisms are still unclear. We revealed that coregulation of
      the HCV-specific T-cell responses in blood of 43 chronic HCV patients showed a
      highly heterogeneous pattern before, during and after PegIFN-alpha/ribavirin.
      Prior to treatment, IL-10 mediated suppression of HCV-specific IFN-gamma
      production in therapy-naive chronic HCV patients was associated with higher HCV
      RNA loads, which suggests that protective antiviral immunity is controlled by IL
      10. In addition, as a consequence of PegIFN-alpha/ribavirin therapy, negative
      regulation of especially HCV-specific IFN-gamma production by TGF-beta and IL-10
      changed dramatically. Our findings emphasize the importance of negative
      regulation for the dysfunctional HCV-specific immunity, which should be
      considered in the design of future immunomodulatory therapies.

PMID- 23145170
TI  - Induction of brain microvascular endothelial cell urokinase expression by
      Cryptococcus neoformans facilitates blood-brain barrier invasion.
AB  - The invasive ability of the blood-borne fungal pathogen Cryptococcus neoformans
      can be enhanced through interactions with host plasma components, such as
      plasminogen. Previously we showed by in vitro studies that plasminogen coats the
      surface of C. neoformans and is converted to the active serine protease, plasmin,
      by host plasminogen activators. Viable, but not formaldehyde- or sodium azide
      killed, cryptococcal strains undergo brain microvascular endothelial cell
      dependent plasminogen-to-plasmin activation, which results in enhanced, plasmin
      dependent cryptococcal invasion of primary bovine brain microvascular endothelial
      cells and fungal ability to degrade plasmin substrates. In the present work,
      brain microvascular endothelial cells cultured with viable, but not killed,
      cryptococcal strains led to significant increases in both urokinase mRNA
      transcription and cell-associated urokinase protein expression. Soluble urokinase
      was also detected in conditioned medium from brain microvascular endothelial
      cells cultured with viable, but not killed, C. neoformans. Exposure of
      plasminogen pre-coated viable C. neoformans to conditioned medium from strain
      matched brain microvascular endothelial cell-fungal co-cultures resulted in
      plasminogen-to-plasmin activation and plasmin-dependent cryptococcal invasion.
      siRNA-mediated silencing of urokinase gene expression or the use of specific
      inhibitors of urokinase activity abrogated both plasminogen-to-plasmin activation
      on C. neoformans and cryptococcal-brain microvascular endothelial cell invasion.
      Our results suggest that pathogen exploitation of the host urokinase
      plasmin(ogen) system may contribute to C. neoformans virulence during invasive
      cryptococcosis.

PMID- 23145171
TI  - Lymphoma-like T cell infiltration in liver is associated with increased copy
      number of dominant negative form of TGFbeta receptor II.
AB  - Hepatosplenic T cell lymphoma (HSTCL) is a distinct and lethal subtype of
      peripheral T cell lymphoma with an aggressive course and poor outcome despite
      multiagent chemotherapy. Contradictory literature, an unknown etiology, and poor
      response to treatment highlight the need to define the malignant process and
      identify molecular targets with potential for successful therapeutic
      interventions. Herein, we report that mice homozygously expressing a dominant
      negative TGFbetaRII (dnTGFbetaRII) under the control of the CD4 promoter
      spontaneously develop lymphoma-like T cell infiltration involving both spleen and
      liver. Splenomegaly, hepatomegaly and liver dysfunction were observed in
      homozygous dnTGFbetaRII mice between 10 weeks and 10 months of age associated
      with a predominant infiltration of CD4(-)CD8(-)TCRbeta(+)NK1.1(+) or
      CD8(+)TCRbeta(+)NK1.1(-) T cell subsets. Notch 1 and c-Myc expression at the mRNA
      levels were significantly increased and positively correlated with the cell
      number of lymphoid infiltrates in the liver of dnTGFbetaRII homozygous compared
      to hemizygous mice. Further, 2*10(4) isolated lymphoma-like cells transplant
      disease by adoptive cell transfers. Collectively, our data demonstrate that
      increased copy number of dnTGFbetaRII is critical for development of lymphoma
      like T cell infiltration.

PMID- 23145172
TI  - Sphingosine 1-phosphate modulates antigen capture by murine Langerhans cells via
      the S1P2 receptor subtype.
AB  - Dendritic cells (DCs) play a pivotal role in the development of cutaneous contact
      hypersensitivity (CHS) and atopic dermatitis as they capture and process antigen
      and present it to T lymphocytes in the lymphoid organs. Recently, it has been
      indicated that a topical application of the sphingolipid sphingosine 1-phosphate
      (S1P) prevents the inflammatory response in CHS, but the molecular mechanism is
      not fully elucidated. Here we indicate that treatment of mice with S1P is
      connected with an impaired antigen uptake by Langerhans cells (LCs), the initial
      step of CHS. Most of the known actions of S1P are mediated by a family of five
      specific G protein-coupled receptors. Our results indicate that S1P inhibits
      macropinocytosis of the murine LC line XS52 via S1P(2) receptor stimulation
      followed by a reduced phosphatidylinositol 3-kinase (PI3K) activity. As down
      regulation of S1P(2) not only diminished S1P-mediated action but also enhanced
      the basal activity of LCs on antigen capture, an autocrine action of S1P has been
      assumed. Actually, S1P is continuously produced by LCs and secreted via the ATP
      binding cassette transporter ABCC1 to the extracellular environment.
      Consequently, inhibition of ABCC1, which decreased extracellular S1P levels,
      markedly increased the antigen uptake by LCs. Moreover, stimulation of
      sphingosine kinase activity, the crucial enzyme for S1P formation, is connected
      not only with enhanced S1P levels but also with diminished antigen capture. These
      results indicate that S1P is essential in LC homeostasis and influences skin
      immunity. This is of importance as previous reports suggested an alteration of
      S1P levels in atopic skin lesions.

PMID- 23145173
TI  - Cbl-c ubiquitin ligase activity is increased via the interaction of its RING
      finger domain with a LIM domain of the paxillin homolog, Hic 5.
AB  - Cbl proteins (Cbl, Cbl-b and Cbl-c) are ubiquitin ligases that are critical
      regulators of tyrosine kinase signaling. In this study we identify a new Cbl-c
      interacting protein, Hydrogen peroxide Induced Construct 5 (Hic-5). The two
      proteins interact through a novel interaction mediated by the RING finger of Cbl
      c and the LIM2 domain of Hic-5. Further, this interaction is mediated and
      dependent on specific zinc coordinating complexes within the RING finger and LIM
      domain. Binding of Hic-5 to Cbl-c leads to an increase in the ubiquitin ligase
      activity of Cbl-c once Cbl-c has been activated by Src phosphorylation or through
      an activating phosphomimetic mutation. In addition, co-transfection of Hic-5 with
      Cbl-c leads to an increase in Cbl-c mediated ubiquitination of the EGFR. These
      data suggest that Hic-5 enhances Cbl-c ubiquitin ligase activity once Cbl-c has
      been phosphorylated and activated. Interactions between heterologous RING fingers
      have been shown to activate E3s. This is the first demonstration of enhancement
      of ubiquitin ligase activity of a RING finger ubiquitin ligase by the direct
      interaction of a LIM zinc coordinating domain.

PMID- 23145174
TI  - Evaluation of dermal substitute in a novel co-transplantation model with
      autologous epidermal sheet.
AB  - The development of more and more new dermal substitutes requires a reliable and
      effective animal model to evaluate their safety and efficacy. In this study we
      constructed a novel animal model using co-transplantation of autologous epidermal
      sheets with dermal substitutes to repair full-thickness skin defects. Autologous
      epidermal sheets were obtained by digesting the basement membrane (BM) and dermal
      components from rat split-thickness skins in Dispase II solution (1.2 u/ml) at 4 
      degrees C for 8, 10 and 12 h. H&E, immunohistochemical and live/dead staining
      showed that the epidermal sheet preserved an intact epidermis without any BM or
      dermal components, and a high percentage of viable cells (92.10 +/- 4.19%) and
      P63 positive cells (67.43 +/- 4.21%) under an optimized condition. Porcine
      acellular dermal matrixes were co-transplanted with the autologous epidermal
      sheets to repair full-thickness skin defects in Sprague-Dawley rats. The
      epidermal sheets survived and completely re-covered the wounds within 3 weeks.
      Histological staining showed that the newly formed stratified epidermis attached
      directly onto the dermal matrix. Inflammatory cell infiltration and
      vascularization of the dermal matrix were not significantly different from those
      in the subcutaneous implantation model. Collagen IV and laminin distributed
      continuously at the epidermis and dermal matrix junction 4 weeks after
      transplantation. Transmission electron microscopy further confirmed the presence
      of continuous lamina densa and hemidesmosome structures. This novel animal model
      can be used not only to observe the biocompatibility of dermal substitutes, but
      also to evaluate their effects on new epidermis and BM formation. Therefore, it
      is a simple and reliable model for evaluating the safety and efficacy of dermal
      substitutes.

PMID- 23145175
TI  - Molecular and pharmacological characterization of serotonin 5-HT2alpha and 5-HT7
      receptors in the salivary glands of the blowfly Calliphora vicina.
AB  - Secretion in blowfly (Calliphora vicina) salivary glands is stimulated by the
      biogenic amine serotonin (5-hydroxytryptamine, 5-HT), which activates both
      inositol 1,4,5-trisphosphate (InsP(3))/Ca(2+) and cyclic adenosine 3',5'
      monophosphate (cAMP) signalling pathways in the secretory cells. In order to
      characterize the signal-inducing 5-HT receptors, we cloned two cDNAs (Cv5
      ht2alpha, Cv5-ht7) that share high similarity with mammalian 5-HT(2) and 5-HT(7)
      receptor genes, respectively. RT-PCR demonstrated that both receptors are
      expressed in the salivary glands and brain. Stimulation of Cv5-ht2alpha
      transfected mammalian cells with 5-HT elevates cytosolic [Ca(2+)] in a dose
      dependent manner (EC(50) = 24 nM). In Cv5-ht7-transfected cells, 5-HT produces a
      dose-dependent increase in [cAMP](i) (EC(50) = 4 nM). We studied the
      pharmacological profile for both receptors. Substances that appear to act as
      specific ligands of either Cv5-HT(2alpha) or Cv5-HT(7) in the heterologous
      expression system were also tested in intact blowfly salivary gland preparations.
      We observed that 5-methoxytryptamine (100 nM) activates only the Cv5-HT(2alpha)
      receptor, 5-carboxamidotryptamine (300 nM) activates only the Cv5-HT(7) receptor,
      and clozapine (1 uM) antagonizes the effects of 5-HT via Cv5-HT(7) in blowfly
      salivary glands, providing means for the selective activation of each of the two
      5-HT receptor subtypes. This study represents the first comprehensive molecular
      and pharmacological characterization of two 5-HT receptors in the blowfly and
      permits the analysis of the physiological role of these receptors, even when co
      expressed in cells, and of the modes of interaction between the Ca(2+)- and cAMP
      signalling cascades.

PMID- 23145176
TI  - The mitochondrial genomes of Nuttalliella namaqua (Ixodoidea: Nuttalliellidae)
      and Argas africolumbae (Ixodoidae: Argasidae): estimation of divergence dates for
      the major tick lineages and reconstruction of ancestral blood-feeding characters.
AB  - Ixodida are composed of hard (Ixodidae), soft (Argasidae) and the monotypic
      Nuttalliellidae (Nuttalliella namaqua) tick families. Nuclear 18S rRNA analysis
      suggested that N. namaqua was the closest extant relative to the last common
      ancestral tick lineage. The mitochondrial genomes of N. namaqua and Argas
      africolumbae were determined using next generation sequencing and de novo
      assembly to investigate this further. The latter was included since previous
      estimates on the divergence times of argasids lacked data for this major genus.
      Mitochondrial gene order for both was identical to that of the Argasidae and
      Prostriata. Bayesian analysis of the COI, Cytb, ND1, ND2 and ND4 genes confirmed
      the monophyly of ticks, the basal position of N. namaqua to the other tick
      families and the accepted systematic relationships of the other tick genera.
      Molecular clock estimates were derived for the divergence of the major tick
      lineages and supported previous estimates on the origins of ticks in the
      Carboniferous. N. namaqua larvae fed successfully on lizards and mice in a
      prolonged manner similar to many argasids and all ixodids. Excess blood meal
      derived water was secreted via the salivary glands, similar to ixodids. We
      propose that this prolonged larval feeding style eventually gave rise to the long
      feeding periods that typify the single larval, nymphal and adult stages of ixodid
      ticks and the associated secretion of water via the salivary glands. Ancestral
      reconstruction of characters involved in blood-feeding indicates that most of the
      characteristics unique to either hard or soft tick families were present in the
      ancestral tick lineage.

PMID- 23145177
TI  - Loss of imprinting and allelic switching at the DLK1-MEG3 locus in human
      hepatocellular carcinoma.
AB  - Deregulation of imprinted genes is an important molecular mechanism contributing
      to the development of cancer in humans. However, knowledge about imprinting
      defects in human hepatocellular carcinoma (HCC), the third leading cause of
      cancer mortality worldwide, is still limited. Therefore, a systematic meta
      analysis of the expression of 223 imprinted loci in human HCC was initiated. This
      screen revealed that the DLK1-MEG3 locus is frequently deregulated in HCC.
      Deregulation of DLK1 and MEG3 expression accompanied by extensive aberrations in
      DNA methylation could be confirmed experimentally in an independent series of
      human HCC (n = 40) in more than 80% of cases. Loss of methylation at the DLK1
      MEG3 locus correlates linearly with global loss of DNA methylation in HCC (r(2) =
      0.63, p<0.0001). Inhibition of DNMT1 in HCC cells using siRNA led to a reduction
      in MEG3-DMR methylation and concomitant increase in MEG3 RNA expression. Allele
      specific expression analysis identified loss of imprinting in 10 out of 31
      informative samples (32%), rendering it one of the most frequent molecular
      defects in human HCC. In 2 cases unequivocal gain of bi-allelic expression
      accompanied by substantial loss of methylation at the IG-DMR could be
      demonstrated. In 8 cases the tumour cells displayed allelic switching by mono
      allelic expression of the normally imprinted allele. Allelic switching was
      accompanied by gains or losses of DNA methylation primarily at IG-DMR1. Analysis
      of 10 hepatocellular adenomas (HCA) and 5 cases of focal nodular hyperplasia
      (FNH) confirmed that this epigenetic instability is specifically associated with
      the process of malignant transformation and not linked to increased proliferation
      per se. This widespread imprint instability in human HCC has to be considered in
      order to minimize unwanted side-effects of therapeutic approaches targeting the
      DNA methylation machinery. It might also serve in the future as predictive
      biomarker and for monitoring response to epigenetic therapy.

PMID- 23145179
TI  - Diversification and population structure in common beans (Phaseolus vulgaris L.).
AB  - Wild accessions of crops and landraces are valuable genetic resources for plant
      breeding and for conserving alleles and gene combinations in planta. The primary
      genepool of cultivated common beans includes wild accessions of Phaseolus
      vulgaris. These are of the same species as the domesticates and therefore are
      easily crossable with cultivated accessions. Molecular marker assessment of wild
      beans and landraces is important for the proper utilization and conservation of
      these important genetic resources. The goal of this research was to evaluate a
      collection of wild beans with fluorescent microsatellite or simple sequence
      repeat markers and to determine the population structure in combination with
      cultivated beans of all known races. Marker diversity in terms of average number
      of alleles per marker was high (13) for the combination of 36 markers and 104
      wild genotypes that was similar to the average of 14 alleles per marker found for
      the 606 cultivated genotypes. Diversity in wild beans appears to be somewhat
      higher than in cultivated beans on a per genotype basis. Five populations or
      genepools were identified in structure analysis of the wild beans corresponding
      to segments of the geographical range, including Mesoamerican (Mexican),
      Guatemalan, Colombian, Ecuadorian-northern Peruvian and Andean (Argentina,
      Bolivia and Southern Peru). The combined analysis of wild and cultivated
      accessions showed that the first and last of these genepools were related to the
      cultivated genepools of the same names and the penultimate was found to be
      distinct but not ancestral to the others. The Guatemalan genepool was very novel
      and perhaps related to cultivars of race Guatemala, while the Colombian
      population was also distinct. Results suggest geographic isolation, founder
      effects or natural selection could have created the different semi-discrete
      populations of wild beans and that multiple domestications and introgression were
      involved in creating the diversity of cultivated beans.

PMID- 23145178
TI  - Phylogeography of bivalve Cyclina sinensis: testing the historical glaciations
      and Changjiang River outflow hypotheses in northwestern Pacific.
AB  - BACKGROUND: The marginal seas of northwestern Pacific are characterized by unique
      topography and intricate hydrology. Two hypotheses have been proposed to explain
      genetic patterns of marine species inhabiting the region: the historical
      glaciations hypothesis suggests population genetic divergence between sea basins,
      whereas the Changjiang River outflow hypothesis suggests genetic break in line
      with the Changjiang Estuary. Here the phylogeography of bivalve Cyclina sinensis
      was investigated to test the validity of these two hypotheses for intertidal
      species in three marginal seas-the East China Sea (ECS), the South China Sea
      (SCS), and the Japan Sea (JPS). METHODOLOGY/PRINCIPAL FINDINGS: Fragments of two
      markers (mitochondrial COI and nuclear ITS-1) were sequenced for 335 individuals
      collected from 21 populations. Significant pairwise Phi(ST) were observed between
      different marginal sea populations. Network analyses illustrated restricted
      distribution of haplogroups/sub-haplogroups to sea basins, with a narrow
      secondary contact zone between the ECS and SCS. Demographic expansion was
      inferred for ECS and SCS lineages using mismatch distributions, neutral tests,
      and extended Bayesian Skyline Plots. Based on a molecular clock method, the
      divergence times among COI lineages were estimated dating from the Pleistocene.
      CONCLUSIONS: The phylogeographical break revealed for C. sinensis populations is
      congruent with the historical isolation of sea basins rather than the putative
      Changjiang River outflow barrier. The large land bridges extending between seas
      during glaciation allowed accumulation of mutations and subsequently gave rise to
      deep divergent lineages. The low-dispersal capacity of the clam and coastal
      oceanography may facilitate the maintenance of the historical patterns as
      barriers shift. Our study supports the historical glaciations hypothesis for
      interpreting present-day phylogeographical patterns of C. sinensis, and
      highlights the importance of historical glaciations for generating genetic
      structure of marine coastal species especially those with low-dispersal abilities
      in northwestern Pacific.

PMID- 23145180
TI  - Development of self-compatible B. rapa by RNAi-mediated S locus gene silencing.
AB  - The self-incompatibility (SI) system is genetically controlled by a single
      polymorphic locus known as the S-locus in the Brassicaceae. Pollen rejection
      occurs when the stigma and pollen share the same S-haplotype. Recognition of S
      haplotype specificity has recently been shown to involve at least two S-locus
      genes, S-receptor kinase (SRK) and S-locus protein 11 or S locus Cysteine-rich
      (SP11/SCR) protein. Here, we examined the function of S(60), one SP11/SCR allele
      of B. rapa cv. Osome, using a RNAi-mediated gene silencing approach. The
      transgenic RNAi lines were highly self-compatible, and this trait was stable in
      subsequent generations, even after crossing with other commercial lines. These
      findings also suggested that the resultant self-compatibility could be
      transferred to commercial cultivars with the desired performances in B. rapa.

PMID- 23145181
TI  - Feeding healthy beagles medium-chain triglycerides, fish oil, and carnitine
      offsets age-related changes in serum fatty acids and carnitine metabolites.
AB  - The purpose of this study was to determine if feeding dogs medium-chain
      triglycerides (MCT), fish oil, and L-carnitine enriched foods offsets age
      associated changes in serum fatty acids (FA) and carnitine metabolites. Forty-one
      healthy Beagles, mean age 9.9 years (range 3.1 to 14.8), were fed control or one
      of two treatment foods for 6 months. All foods were complete and balanced and met
      the nutrient requirements for adult dogs, and had similar concentrations of
      moisture, protein, and fat (approx. 7.4%, 14.0%, and 18.1%, respectively). The
      treatment diets both contained added L-carnitine (300 mg/kg) and 0.6% (treatment
      food 1) or 1.5% (treatment food 2) added fish oil. Treatment food 2 also had
      increased MCT from coconut oil, added corn oil, and reduced animal fat.
      Composition of serum FA was determined by gas chromatography of FA methyl esters.
      Metabolomic profiles of serum samples were determined from extracted supernatants
      that were split and run on GC/MS and LC/MS/MS platforms, for identification and
      relative quantification of small metabolites. Body composition was determined by
      dual energy x-ray absorptiometry. Among dog groups, there was no change in total
      lean-body weight, or in serum total protein and serum albumin concentrations,
      based on time or dietary treatment. Serum concentrations of carnitine metabolites
      were decreased in geriatric (>7 years) vs. mature adult (<= 7 years) dogs, and
      supplementation with L-carnitine attenuated the effects of aging. The ratio of
      PUFA to SFA was significantly greater in mature dogs at baseline (P <= 0.05).
      Serum concentrations of eicosapentaenoic and docosahexaenoic FA increased in a
      dose-dependent manner. Dogs consuming treatment food 2 also had increased serum
      concentrations of lauric and myristic FA, and decreased concentrations of SFA,
      MUFA, and arachidonate (all P <= 0.05) and their PUFA to SFA ratio increased. In
      summary, dietary MCT, fish oil, and L-carnitine counterbalanced the effects of
      aging on circulating concentrations of these compounds.

PMID- 23145183
TI  - Expression of concern: The PHA-skin test reflects acquired T-cell mediated
      immunocompetence in birds.

PMID- 23145182
TI  - Carboxylesterase1/Esterase-x regulates chylomicron production in mice.
AB  - Elevated postprandial plasma triacylglycerol (TG) concentrations are commonly
      associated with obesity and the risk of cardiovascular disease. Dietary fat
      contributes to this condition through the production of chylomicrons.
      Carboxylesterases have been mainly studied for their role in drug metabolism, but
      recently they have been shown to participate in lipid metabolism; however, their
      role in intestinal lipid metabolism is unknown. Carboxylesterase1/esterase-x
      (Ces1/Es-x) deficient mice become obese, hyperlipidemic and develop hepatic
      steatosis even on standard chow diet. Here, we aimed to explore the role of
      Ces1/Es-x in intestinal lipid metabolism. Six-month old wild-type and Ces1/Es-x
      deficient mice were maintained on chow diet and intestinal lipid metabolism and
      plasma chylomicron clearance were analyzed. Along the intestine Ces1/Es-x protein
      is expressed only in proximal jejunum. Ablation of Ces1/Es-x expression results
      in postprandial hyperlipidemia due to increased secretion of chylomicrons. The
      secreted chylomicrons have aberrant protein composition, which results in their
      reduced clearance. In conclusion, Ces1/Es-x participates in the regulation of
      chylomicron assembly and secretion. Ces1/Es-x might act as a lipid sensor in
      enterocytes regulating chylomicron secretion rate. Ces1/Es-x might represent an
      attractive pharmacological target for the treatment of lipid abnormalities
      associated with obesity, insulin resistance and fatty liver disease.

PMID- 23145184
TI  - Expression of concern: Novel allelic variants in the canine cyclooxgenase-2 (Cox
      2) promoter are associated with renal dysplasia in dogs.

PMID- 23145185
TI  - Acute lung, heart, liver, and pancreatic involvements with hyponatremia and
      retinochoroiditis in a 33-year-old French Guianan patient.

PMID- 23145186
TI  - Analysis of neglected tropical disease drug and vaccine development pipelines to
      predict issuance of FDA priority review vouchers over the next decade.

PMID- 23145187
TI  - Agrochemicals against malaria, sleeping sickness, leishmaniasis and Chagas
      disease.
AB  - In tropical regions, protozoan parasites can cause severe diseases with malaria,
      leishmaniasis, sleeping sickness, and Chagas disease standing in the forefront.
      Many of the drugs currently being used to treat these diseases have been
      developed more than 50 years ago and can cause severe adverse effects. Above all,
      resistance to existing drugs is widespread and has become a serious problem
      threatening the success of control measures. In order to identify new
      antiprotozoal agents, more than 600 commercial agrochemicals have been tested on
      the pathogens causing the above mentioned diseases. For all of the pathogens,
      compounds were identified with similar or even higher activities than the
      currently used drugs in applied in vitro assays. Furthermore, in vivo activity
      was observed for the fungicide/oomyceticide azoxystrobin, and the insecticide
      hydramethylnon in the Plasmodium berghei mouse model, and for the oomyceticide
      zoxamide in the Trypanosoma brucei rhodesiense STIB900 mouse model, respectively.

PMID- 23145188
TI  - Bartonella bacilliformis: a systematic review of the literature to guide the
      research agenda for elimination.
AB  - BACKGROUND: Carrion's disease affects small Andean communities in Peru, Colombia
      and Ecuador and is characterized by two distinct disease manifestations: an
      abrupt acute bacteraemic illness (Oroya fever) and an indolent cutaneous eruptive
      condition (verruga Peruana). Case fatality rates of untreated acute disease can
      exceed 80% during outbreaks. Despite being an ancient disease that has affected
      populations since pre-Inca times, research in this area has been limited and
      diagnostic and treatment guidelines are based on very low evidence reports. The
      apparently limited geographical distribution and ecology of Bartonella
      bacilliformis may present an opportunity for disease elimination if a clear
      understanding of the epidemiology and optimal case and outbreak management can be
      gained. METHODS: All available databases were searched for English and Spanish
      language articles on Carrion's disease. In addition, experts in the field were
      consulted for recent un-published work and conference papers. The highest level
      evidence studies in the fields of diagnostics, treatment, vector control and
      epidemiology were critically reviewed and allocated a level of evidence, using
      the Oxford Centre for Evidence-Based Medicine (CEBM) guidelines. RESULTS: A total
      of 44 studies were considered to be of sufficient quality to be included in the
      analysis. The majority of these were level 4 or 5 (low quality) evidence and
      based on small sample sizes. Few studies had been carried out in endemic areas.
      CONCLUSIONS: Current approaches to the diagnosis and management of Carrion's
      disease are based on small retrospective or observational studies and expert
      opinion. Few studies take a public health perspective or examine vector control
      and prevention. High quality studies performed in endemic areas are required to
      define optimal diagnostic and treatment strategies.

PMID- 23145189
TI  - Whole genome analysis of Leptospira licerasiae provides insight into leptospiral
      evolution and pathogenicity.
AB  - The whole genome analysis of two strains of the first intermediately pathogenic
      leptospiral species to be sequenced (Leptospira licerasiae strains VAR010 and
      MMD0835) provides insight into their pathogenic potential and deepens our
      understanding of leptospiral evolution. Comparative analysis of eight leptospiral
      genomes shows the existence of a core leptospiral genome comprising 1547 genes
      and 452 conserved genes restricted to infectious species (including L.
      licerasiae) that are likely to be pathogenicity-related. Comparisons of the
      functional content of the genomes suggests that L. licerasiae retains several
      proteins related to nitrogen, amino acid and carbohydrate metabolism which might
      help to explain why these Leptospira grow well in artificial media compared with
      pathogenic species. L. licerasiae strains VAR010(T) and MMD0835 possess two
      prophage elements. While one element is circular and shares homology with LE1 of
      L. biflexa, the second is cryptic and homologous to a previously identified but
      unnamed region in L. interrogans serovars Copenhageni and Lai. We also report a
      unique O-antigen locus in L. licerasiae comprised of a 6-gene cluster that is
      unexpectedly short compared with L. interrogans in which analogous regions may
      include >90 such genes. Sequence homology searches suggest that these genes were
      acquired by lateral gene transfer (LGT). Furthermore, seven putative genomic
      islands ranging in size from 5 to 36 kb are present also suggestive of antecedent
      LGT. How Leptospira become naturally competent remains to be determined, but
      considering the phylogenetic origins of the genes comprising the O-antigen
      cluster and other putative laterally transferred genes, L. licerasiae must be
      able to exchange genetic material with non-invasive environmental bacteria. The
      data presented here demonstrate that L. licerasiae is genetically more closely
      related to pathogenic than to saprophytic Leptospira and provide insight into the
      genomic bases for its infectiousness and its unique antigenic characteristics.

PMID- 23145191
TI  - Stage progression and neurological symptoms in Trypanosoma brucei rhodesiense
      sleeping sickness: role of the CNS inflammatory response.
AB  - BACKGROUND: Human African trypanosomiasis progresses from an early
      (hemolymphatic) stage, through CNS invasion to the late (meningoencephalitic)
      stage. In experimental infections disease progression is associated with
      neuroinflammatory responses and neurological symptoms, but this concept requires
      evaluation in African trypanosomiasis patients, where correct diagnosis of the
      disease stage is of critical therapeutic importance. METHODOLOGY/PRINCIPAL
      FINDINGS: This was a retrospective study on a cohort of 115 T.b.rhodesiense HAT
      patients recruited in Eastern Uganda. Paired plasma and CSF samples allowed the
      measurement of peripheral and CNS immunoglobulin and of CSF cytokine synthesis.
      Cytokine and immunoglobulin expression were evaluated in relation to disease
      duration, stage progression and neurological symptoms. Neurological symptoms were
      not related to stage progression (with the exception of moderate coma). Increases
      in CNS immunoglobulin, IL-10 and TNF-alpha synthesis were associated with stage
      progression and were mirrored by a reduction in TGF-beta levels in the CSF. There
      were no significant associations between CNS immunoglobulin and cytokine
      production and neurological signs of disease with the exception of moderate coma
      cases. Within the study group we identified diagnostically early stage cases with
      no CSF pleocytosis but intrathecal immunoglobulin synthesis and diagnostically
      late stage cases with marginal CSF pleocytosis and no detectable trypanosomes in
      the CSF. CONCLUSIONS: Our results demonstrate that there is not a direct linkage
      between stage progression, neurological signs of infection and neuroinflammatory
      responses in rhodesiense HAT. Neurological signs are observed in both early and
      late stages, and while intrathecal immunoglobulin synthesis is associated with
      neurological signs, these are also observed in cases lacking a CNS inflammatory
      response. While there is an increase in inflammatory cytokine production with
      stage progression, this is paralleled by increases in CSF IL-10. As stage
      diagnostics, the CSF immunoglobulins and cytokines studied do not have sufficient
      sensitivity to be of clinical value.

PMID- 23145190
TI  - RNAseq analysis of the parasitic nematode Strongyloides stercoralis reveals
      divergent regulation of canonical dauer pathways.
AB  - The infectious form of many parasitic nematodes, which afflict over one billion
      people globally, is a developmentally arrested third-stage larva (L3i). The
      parasitic nematode Strongyloides stercoralis differs from other nematode species
      that infect humans, in that its life cycle includes both parasitic and free
      living forms, which can be leveraged to investigate the mechanisms of L3i arrest
      and activation. The free-living nematode Caenorhabditis elegans has a similar
      developmentally arrested larval form, the dauer, whose formation is controlled by
      four pathways: cyclic GMP (cGMP) signaling, insulin/IGF-1-like signaling (IIS),
      transforming growth factor beta (TGFbeta) signaling, and biosynthesis of
      dafachronic acid (DA) ligands that regulate a nuclear hormone receptor. We
      hypothesized that homologous pathways are present in S. stercoralis, have similar
      developmental regulation, and are involved in L3i arrest and activation. To test
      this, we undertook a deep-sequencing study of the polyadenylated transcriptome,
      generating over 2.3 billion paired-end reads from seven developmental stages. We
      constructed developmental expression profiles for S. stercoralis homologs of C.
      elegans dauer genes identified by BLAST searches of the S. stercoralis genome as
      well as de novo assembled transcripts. Intriguingly, genes encoding cGMP pathway
      components were coordinately up-regulated in L3i. In comparison to C. elegans, S.
      stercoralis has a paucity of genes encoding IIS ligands, several of which have
      abundance profiles suggesting involvement in L3i development. We also identified
      seven S. stercoralis genes encoding homologs of the single C. elegans dauer
      regulatory TGFbeta ligand, three of which are only expressed in L3i. Putative DA
      biosynthetic genes did not appear to be coordinately regulated in L3i
      development. Our data suggest that while dauer pathway genes are present in S.
      stercoralis and may play a role in L3i development, there are significant
      differences between the two species. Understanding the mechanisms governing L3i
      development may lead to novel treatment and control strategies.

PMID- 23145192
TI  - Estimating and mapping the population at risk of sleeping sickness.
AB  - BACKGROUND: Human African trypanosomiasis (HAT), also known as sleeping sickness,
      persists as a public health problem in several sub-Saharan countries. Evidence
      based, spatially explicit estimates of population at risk are needed to inform
      planning and implementation of field interventions, monitor disease trends, raise
      awareness and support advocacy. Comprehensive, geo-referenced epidemiological
      records from HAT-affected countries were combined with human population layers to
      map five categories of risk, ranging from "very high" to "very low," and to
      estimate the corresponding at-risk population. RESULTS: Approximately 70 million
      people distributed over a surface of 1.55 million km(2) are estimated to be at
      different levels of risk of contracting HAT. Trypanosoma brucei gambiense
      accounts for 82.2% of the population at risk, the remaining 17.8% being at risk
      of infection from T. b. rhodesiense. Twenty-one million people live in areas
      classified as moderate to very high risk, where more than 1 HAT case per 10,000
      inhabitants per annum is reported. DISCUSSION: Updated estimates of the
      population at risk of sleeping sickness were made, based on quantitative
      information on the reported cases and the geographic distribution of human
      population. Due to substantial methodological differences, it is not possible to
      make direct comparisons with previous figures for at-risk population. By
      contrast, it will be possible to explore trends in the future. The presented maps
      of different HAT risk levels will help to develop site-specific strategies for
      control and surveillance, and to monitor progress achieved by ongoing efforts
      aimed at the elimination of sleeping sickness.

PMID- 23145193
TI  - Is Chagas disease really the "new HIV/AIDS of the Americas"?

PMID- 23145194
TI  - Now we are six.

PMID- 23145195
TI  - Global burden of human brucellosis: a systematic review of disease frequency.
AB  - BACKGROUND: This report presents a systematic review of scientific literature
      published between 1990-2010 relating to the frequency of human brucellosis,
      commissioned by WHO. The objectives were to identify high quality disease
      incidence data to complement existing knowledge of the global disease burden and,
      ultimately, to contribute towards the calculation of a Disability-Adjusted Life
      Years (DALY) estimate for brucellosis. METHODS/PRINCIPAL FINDINGS: Thirty three
      databases were searched, identifying 2,385 articles relating to human
      brucellosis. Based on strict screening criteria, 60 studies were selected for
      quality assessment, of which only 29 were of sufficient quality for data
      analysis. Data were only available from 15 countries in the regions of Northern
      Africa and Middle East, Western Europe, Central and South America, Sub-Saharan
      Africa, and Central Asia. Half of the studies presented incidence data, six of
      which were longitudinal prospective studies, and half presented seroprevalence
      data which were converted to incidence rates. Brucellosis incidence varied widely
      between, and within, countries. Although study biases cannot be ruled out,
      demographic, occupational, and socioeconomic factors likely play a role.
      Aggregated data at national or regional levels do not capture these complexities
      of disease dynamics and, consequently, at-risk populations or areas may be
      overlooked. In many brucellosis-endemic countries, health systems are weak and
      passively-acquired official data underestimate the true disease burden.
      CONCLUSIONS: High quality research is essential for an accurate assessment of
      disease burden, particularly in Eastern Europe, the Asia-Pacific, Central and
      South America and Africa where data are lacking. Providing formal epidemiological
      and statistical training to researchers is essential for improving study quality.
      An integrated approach to disease surveillance involving both human health and
      veterinary services would allow a better understanding of disease dynamics at the
      animal-human interface, as well as a more cost-effective utilisation of
      resources.

PMID- 23145197
TI  - Controlling dengue with vaccines in Thailand.
AB  - BACKGROUND: Dengue is a mosquito-borne infectious disease that constitutes a
      growing global threat with the habitat expansion of its vectors Aedes aegyti and
      A. albopictus and increasing urbanization. With no effective treatment and
      limited success of vector control, dengue vaccines constitute the best control
      measure for the foreseeable future. With four interacting dengue serotypes, the
      development of an effective vaccine has been a challenge. Several dengue vaccine
      candidates are currently being tested in clinical trials. Before the widespread
      introduction of a new dengue vaccine, one needs to consider how best to use
      limited supplies of vaccine given the complex dengue transmission dynamics and
      the immunological interaction among the four dengue serotypes.
      METHODOLOGY/PRINCIPAL FINDINGS: We developed an individual-level (including both
      humans and mosquitoes), stochastic simulation model for dengue transmission and
      control in a semi-rural area in Thailand. We calibrated the model to dengue
      serotype-specific infection, illness and hospitalization data from Thailand. Our
      simulations show that a realistic roll-out plan, starting with young children
      then covering progressively older individuals in following seasons, could reduce
      local transmission of dengue to low levels. Simulations indicate that this
      strategy could avert about 7,700 uncomplicated dengue fever cases and 220 dengue
      hospitalizations per 100,000 people at risk over a ten-year period.
      CONCLUSIONS/SIGNIFICANCE: Vaccination will have an important role in controlling
      dengue. According to our modeling results, children should be prioritized to
      receive vaccine, but adults will also need to be vaccinated if one wants to
      reduce community-wide dengue transmission to low levels.

PMID- 23145196
TI  - Human macrophage response to L. (Viannia) panamensis: microarray evidence for an
      early inflammatory response.
AB  - BACKGROUND: Previous findings indicate that susceptibility to Leishmania
      (Viannia) panamensis infection of monocyte-derived macrophages from patients and
      asymptomatically infected individuals were associated with the adaptive immune
      response and clinical outcome. METHODOLOGY/PRINCIPAL FINDINGS: To understand the
      basis for this difference we examined differential gene expression of human
      monocyte-derived macrophages following exposure to L. (V.) panamensis. Gene
      activation profiles were determined using macrophages from healthy volunteers
      cultured with or without stationary phase promastigotes of L. (V.) panamensis.
      Significant changes in expression (>1.5-fold change; p<0.05; up- or down
      regulated) were identified at 0.5, 4 and 24 hours. mRNA abundance profiles varied
      over time, with the highest level of activation occurring at earlier time points
      (0.5 and 4 hrs). In contrast to observations for other Leishmania species, most
      significantly changed mRNAs were up- rather than down-regulated, especially at
      early time points. Up-regulated transcripts over the first 24 hours belonged to
      pathways involving eicosanoid metabolism, oxidative stress, activation of PKC
      through G protein coupled receptors, or mechanism of gene regulation by
      peroxisome proliferators via PPARalpha. Additionally, a marked activation of Toll
      receptor mediated pathways was observed. Comparison with published microarray
      data from macrophages infected with L. (Leishmania) chagasi indicate differences
      in the regulation of genes involved in signaling, motility and the immune
      response. CONCLUSIONS: Results show that the early (0.5 to 24 hours) human
      monocyte-derived macrophage response to L. (Viannia) panamensis is not quiescent,
      in contrast to published reports examining later response times (48-96 hours).
      Early macrophage responses are important for the developing cellular response at
      the site of infection. The kinetics and the mRNA abundance profiles induced by L.
      (Viannia) panamensis illustrate the dynamics of these interactions and the
      distinct biologic responses to different Leishmania species from the outset of
      infection within their primary host cell.

PMID- 23145198
TI  - Sensitive and specific immunohistochemical diagnosis of human alveolar
      echinococcosis with the monoclonal antibody Em2G11.
AB  - BACKGROUND: Alveolar echinococcosis (AE) is caused by the metacestode stage of
      Echinococcus multilocularis. Differential diagnosis with cystic echinococcosis
      (CE) caused by E. granulosus and AE is challenging. We aimed at improving
      diagnosis of AE on paraffin sections of infected human tissue by
      immunohistochemical testing of a specific antibody. METHODOLOGY/PRINCIPAL
      FINDINGS: We have analysed 96 paraffin archived specimens, including 6 cutting
      needle biopsies and 3 fine needle aspirates, from patients with suspected AE or
      CE with the monoclonal antibody (mAb) Em2G11 specific for the Em2 antigen of E.
      multilocularis metacestodes. In human tissue, staining with mAb Em2G11 is highly
      specific for E. multilocularis metacestodes while no staining is detected in CE
      lesions. In addition, the antibody detects small particles of E. multilocularis
      (spems) of less than 1 um outside the main lesion in necrotic tissue, liver
      sinusoids and lymphatic tissue most probably caused by shedding of parasitic
      material. The conventional histological diagnosis based on haematoxylin and eosin
      and PAS stainings were in accordance with the immunohistological diagnosis using
      mAb Em2G11 in 90 of 96 samples. In 6 samples conventional subtype diagnosis of
      echinococcosis had to be adjusted when revised by immunohistology with mAb
      Em2G11. CONCLUSIONS/SIGNIFICANCE: Immunohistochemistry with the mAb Em2G11 is a
      new, highly specific and sensitive diagnostic tool for AE. The staining of small
      particles of E. multilocularis (spems) outside the main lesion including
      immunocompetent tissue, such as lymph nodes, suggests a systemic effect on the
      host.

PMID- 23145199
TI  - Diagnosing and staging of cystic echinococcosis: how do CT and MRI perform in
      comparison to ultrasound?
AB  - BACKGROUND: Imaging plays the key role in diagnosing and staging of CE. The
      description of CE-specific imaging features and the WHO CE cyst classification is
      based on ultrasound. The reproducibility of the ultrasound-defined features of CE
      cysts is variable in MR- and CT-imaging. This is of particular importance for
      cysts that are not accessible by US and because of the increasing availability
      and overuse of CT and MR imaging. METHODOLOGY/PRINCIPAL FINDINGS: Retrospective
      analysis of patients with abdominal CE cysts of an interdisciplinary CE clinic
      who had CT and/or MRI scans performed additionally to US imaging. All images were
      read and interpreted by the same senior radiologist experienced in the diagnosis
      of CE. US, CT and MR images were staged according to the WHO classification
      criteria. The agreement beyond chance was quantified by kappa coefficients
      (kappa). 107 patients with 187 CE cysts met the inclusion criteria. All cysts
      were assessed by US, 138 by CT, and 125 by MRI. The level of agreement beyond
      chance of the individual CE stages 1-4 was clearly lower for CT, with kappa
      ranging from 0.62 to 0.72, compared to MRI with values of kappa between 0.83 and
      1.0. For CE5 cysts CT (kappa = 0.95) performed better than MRI (kappa = 0.65).
      CONCLUSIONS: Ultrasound remains the corner stone of diagnosis, staging and follow
      up of CE cysts. MRI reproduces the ultrasound-defined features of CE better than
      CT. If US cannot be performed due to cyst location or patient-specific reasons
      MRI with heavily T2-weighted series is preferable to CT.

PMID- 23145201
TI  - A systematic review of high quality diagnostic tests for Chagas disease.
AB  - BACKGROUND: There is significant heterogeneity in reported sensitivities and
      specificities of diagnostic serological assays for Chagas disease, as might be
      expected from studies that vary widely according to setting, research design,
      antigens employed, and reference standard. The purpose of this study is to
      summarize the reported accuracy of serological assays and to identify sources of
      heterogeneity including quality of research design. To avoid associated spectrum
      bias, our analysis was limited to cohort studies. METHODS: We completed a search
      of PubMed, a bibliographic review of potentially relevant articles, and a review
      of articles identified by a study author involved in this area of research.
      Studies were limited to prospective cohort studies of adults published since
      1985. Measures of diagnostic accuracy were pooled using a Der Simonian Laird
      Random Effects Model. A subgroup analysis and meta regression were employed to
      identify sources of heterogeneity. The QUADAS tool was used to assess quality of
      included studies and Begg's funnel plot was used to assess publication bias.
      RESULTS: Eighteen studies and 61 assays were included in the final analysis.
      Significant heterogeneity was found in all pre-determined subgroups. Overall
      sensitivity was 90% (95% CI: 89%-91%) and overall specificity was 98% (95% CI:
      98%-98%). CONCLUSION: Sensitivity and specificity of serological assays for the
      diagnosis of Chagas disease appear less accurate than previously thought.
      Suggestions to improve the accuracy of reporting include the enrollment of
      patients in a prospective manner, double blinding, and providing an explicit
      method of addressing subjects that have an indeterminate diagnosis by either the
      reference standard or index test.

PMID- 23145200
TI  - Genetic diversity within Schistosoma haematobium: DNA barcoding reveals two
      distinct groups.
AB  - BACKGROUND: Schistosomiasis in one of the most prevalent parasitic diseases,
      affecting millions of people and animals in developing countries. Amongst the
      human-infective species S. haematobium is one of the most widespread causing
      urogenital schistosomiasis, a major human health problem across Africa, however
      in terms of research this human pathogen has been severely neglected.
      METHODOLOGY/PRINCIPAL FINDINGS: To elucidate the genetic diversity of Schistosoma
      haematobium, a DNA 'barcoding' study was performed on parasite material collected
      from 41 localities representing 18 countries across Africa and the Indian Ocean
      Islands. Surprisingly low sequence variation was found within the mitochondrial
      cytochrome oxidase subunit I (cox1) and the NADH-dehydrogenase subunit 1 snad1).
      The 61 haplotypes found within 1978 individual samples split into two distinct
      groups; one (Group 1) that is predominately made up of parasites from the African
      mainland and the other (Group 2) that is made up of samples exclusively from the
      Indian Ocean Islands and the neighbouring African coastal regions. Within Group 1
      there was a dominance of one particular haplotype (H1) representing 1574 (80%) of
      the samples analyzed. Population genetic diversity increased in samples collected
      from the East African coastal regions and the data suggest that there has been
      movement of parasites between these areas and the Indian Ocean Islands.
      CONCLUSIONS/SIGNIFICANCE: The high occurrence of the haplotype (H1) suggests that
      at some point in the recent evolutionary history of S. haematobium in Africa the
      population may have passed through a genetic 'bottleneck' followed by a
      population expansion. This study provides novel and extremely interesting
      insights into the population genetics of S. haematobium on a large geographic
      scale, which may have consequence for control and monitoring of urogenital
      schistosomiasis.

PMID- 23145202
TI  - Chitinase 3-like 1 protein levels are elevated in Schistosoma haematobium
      infected children.
AB  - BACKGROUND: Currently there are few studies characterising the nature and
      aetiology of human schistosome-related inflammatory processes. The aim of this
      study was to determine the relationship between Chitinase 3-like 1 (CHI3L1), also
      known as YKL-40, a molecule associated with inflammatory processes, and
      schistosome infection, morbidity and systemic cytokine levels. METHODS:
      Serological levels of CHI3L1 and a panel of cytokines (IFN-y, IL-4/5/6/9/10/13
      and 17) were measured in two Zimbabwean populations resident in a high and low
      schistosome infection area. CHI3L1 levels were related to schistosome infection,
      haematuria status and cytokine levels after allowing for confounding variables.
      The effect of antihelminthic treatment with praziquantel on CHI3L1 levels was
      determined in 246 participants 6 weeks post-treatment. RESULTS: CHI3L1 levels
      increased with age in both areas but were significantly higher in the high
      infection areas compared to the low infection area. CHI3L1 levels were also
      higher in infected compared to uninfected individuals with this difference being
      significant in the youngest age group. Curative antihelminthic treatment resulted
      in a significant decrease in CHI3L1 levels. Of the cytokines, only IL-10 and IL
      17 had a significant association with CHI3L1 levels, and this association was
      negative. CONCLUSIONS: Serum CHI3L1 levels differ between infected and uninfected
      people before and after antihelminthic treatment. The greatest difference occurs
      in the youngest age group, in keeping with the period when schistosome-related
      pathological processes are initiated. Following from previous studies in non
      infectious diseases showing that CHI3L1 is a biomarker for the inflammatory
      process, this study suggests that the potential for CHI3L1 as a biomarker for
      schistosome-related pathology should be explored further.

PMID- 23145203
TI  - Mechanistic and single-dose in vivo therapeutic studies of Cry5B anthelmintic
      action against hookworms.
AB  - BACKGROUND: Hookworm infections are one of the most important parasitic
      infections of humans worldwide, considered by some second only to malaria in
      associated disease burden. Single-dose mass drug administration for soil
      transmitted helminths, including hookworms, relies primarily on albendazole,
      which has variable efficacy. New and better hookworm therapies are urgently
      needed. Bacillus thuringiensis crystal protein Cry5B has potential as a novel
      anthelmintic and has been extensively studied in the roundworm Caenorhabditis
      elegans. Here, we ask whether single-dose Cry5B can provide therapy against a
      hookworm infection and whether C. elegans mechanism-of-action studies are
      relevant to hookworms. METHODOLOGY/PRINCIPAL FINDINGS: To test whether the C.
      elegans invertebrate-specific glycolipid receptor for Cry5B is relevant in
      hookworms, we fed Ancylostoma ceylanicum hookworm adults Cry5B with and without
      galactose, an inhibitor of Cry5B-C. elegans glycolipid interactions. As with C.
      elegans, galactose inhibits Cry5B toxicity in A. ceylanicum. Furthermore, p38
      mitogen-activated protein kinase (MAPK), which controls one of the most important
      Cry5B signal transduction responses in C. elegans, is functionally operational in
      hookworms. A. ceylanicum hookworms treated with Cry5B up-regulate p38 MAPK and
      knock down of p38 MAPK activity in hookworms results in hypersensitivity of A.
      ceylanicum adults to Cry5B attack. Single-dose Cry5B is able to reduce by >90% A.
      ceylanicum hookworm burdens from infected hamsters, in the process eliminating
      hookworm egg shedding in feces and protecting infected hamsters from blood loss.
      Anthelmintic activity is increased about 3-fold, eliminating >97% of the
      parasites with a single 3 mg dose (~30 mg/kg), by incorporating a simple
      formulation to help prevent digestion in the acidic stomach of the host mammal.
      CONCLUSIONS/SIGNIFICANCE: These studies advance the development of Cry5B protein
      as a potent, safe single-dose anthelmintic for hookworm therapy and make
      available the information of how Cry5B functions in C. elegans in order to study
      and improve Cry5B function against hookworms.

PMID- 23145204
TI  - Urban cholera transmission hotspots and their implications for reactive
      vaccination: evidence from Bissau city, Guinea bissau.
AB  - BACKGROUND: Use of cholera vaccines in response to epidemics (reactive
      vaccination) may provide an effective supplement to traditional control measures.
      In Haiti, reactive vaccination was considered but, until recently, rejected in
      part due to limited global supply of vaccine. Using Bissau City, Guinea-Bissau as
      a case study, we explore neighborhood-level transmission dynamics to understand
      if, with limited vaccine and likely delays, reactive vaccination can
      significantly change the course of a cholera epidemic. METHODS AND FINDINGS: We
      fit a spatially explicit meta-population model of cholera transmission within
      Bissau City to data from 7,551 suspected cholera cases from a 2008 epidemic. We
      estimated the effect reactive vaccination campaigns would have had on the
      epidemic under different levels of vaccine coverage and campaign start dates. We
      compared highly focused and diffuse strategies for distributing vaccine
      throughout the city. We found wide variation in the efficiency of cholera
      transmission both within and between areas of the city. "Hotspots", where
      transmission was most efficient, appear to drive the epidemic. In particular one
      area, Bandim, was a necessary driver of the 2008 epidemic in Bissau City. If
      vaccine supply were limited but could have been distributed within the first 80
      days of the epidemic, targeting vaccination at Bandim would have averted the most
      cases both within this area and throughout the city. Regardless of the
      distribution strategy used, timely distribution of vaccine in response to an
      ongoing cholera epidemic can prevent cases and save lives. CONCLUSIONS: Reactive
      vaccination can be a useful tool for controlling cholera epidemics, especially in
      urban areas like Bissau City. Particular neighborhoods may be responsible for
      driving a city's cholera epidemic; timely and targeted reactive vaccination at
      such neighborhoods may be the most effective way to prevent cholera cases both
      within that neighborhood and throughout the city.

PMID- 23145205
TI  - EZH2: a pivotal regulator in controlling cell differentiation.
AB  - Epigenetic regulation plays an important role in stem cell self-renewal,
      maintenance and lineage differentiation. The epigenetic profiles of stem cells
      are related to their transcriptional signature. Enhancer of Zeste homlog 2
      (EZH2), a catalytic subunit of epigenetic regulator Polycomb repressive complex 2
      (PRC2), has been shown to be a key regulator in controlling cellular
      differentiation. EZH2 is a histone methyltransferase that not only methylates
      histone H3 on Lys 27 (H3K27me3) but also interacts with and recruits DNA
      methyltransferases to methylate CpG at certain EZH2 target genes to establish
      firm repressive chromatin structures, contributing to tumor progression and the
      regulation of development and lineage commitment both in embryonic stem cells
      (ESCs) and adult stem cells. In addition to its well-recognized epigenetic gene
      silencing function, EZH2 also directly methylates nonhistone targets such as the
      cardiac transcription factor, GATA4, resulting in attenuated GATA4
      transcriptional activity and gene repression. This review addresses recent
      progress toward the understanding of the biological functions and regulatory
      mechanisms of EZH2 and its targets as well as their roles in stem cell
      maintenance and cell differentiation.

PMID- 23145206
TI  - Tumor-associated macrophages: function, phenotype, and link to prognosis in human
      lung cancer.
AB  - Macrophages are the dominant leukocyte population found in the tumor
      microenvironment. Accumulating evidence suggests that these tumor-associated
      macrophages (TAMs) actively promote all aspects of tumor initiation, growth, and
      development. However, TAMs are not a single uniform population; instead, they are
      composed of multiple distinct pro- and anti-tumoral subpopulations with
      overlapping features depending on a variety of external factors. Defining and
      differentiating these subsets remains a challenging work-in-progress. These
      difficulties are apparent in prognostic studies in lung cancer that initially
      demonstrated conflicting evidence regarding the significance of TAMs but which
      have more recently clarified and confirmed the clinical importance of these
      subsets through improved phenotypic capabilities. Thus, these cells represent
      potential targets for cancer therapeutic initiatives through translational
      approaches. In this review, we summarize the current understanding of how the
      tumor microenvironment takes advantage of macrophage plasticity to mold an
      immunosuppressive population, the phenotypic heterogeneity of TAMs, and their
      link to prognosis in human lung cancer.

PMID- 23145207
TI  - The putative G-protein coupled estrogen receptor agonist G-1 suppresses
      proliferation of ovarian and breast cancer cells in a GPER-independent manner.
AB  - G-protein coupled estrogen receptor 1 (GPER) plays an important role in mediating
      estrogen action in many different tissues under both physiological and
      pathological conditions. G-1 (1-[4-(6-bromobenzo[1,3]dioxol-5yl)-3a,4,5,9b
      tetrahydro-3H-cyclopenta [c]quinolin-8-yl]-ethanone) has been developed as a
      selective GPER agonist to distinguish estrogen actions mediated by GPER from
      those mediated by classic estrogen receptors. In the present study, we
      surprisingly found that G-1 suppressed proliferation and induced apoptosis of KGN
      cells (a human ovarian granulosa cell tumor cell line), actions that were not
      blocked by a selective GPER antagonist G15 or siRNA knockdown of GPER. G-1 also
      suppressed proliferation and induced cell apoptosis in GPER-negative HEK-293
      cells and MDA-MB 231 breast cancer cells. Our results demonstrate that G-1
      suppresses proliferation of ovarian and breast cancer cells in a GPER-independent
      manner. G-1 may be a candidate for the development of drugs against ovarian and
      breast cancer.

PMID- 23145208
TI  - Circulating levels of citrullinated and MMP-degraded vimentin (VICM) in liver
      fibrosis related pathology.
AB  - AIM: To investigate whether increased levels of vimentin citrullinated peptides
      identified by MS in articular cartilage can be measured in pathologies other than
      rheumatoid arthritis and be utilised for diagnostic purposes. METHODS: A
      monoclonal antibody against the sequence RLRSSVPGV-citrulline (VICM) was
      developed and evaluated in a carbon tetrachloride (CCl(4)) (n=52 + 28 controls)
      rat model of liver fibrosis and two clinical cohorts of adult patients with
      hepatitis C (HCV) (n=92) and non-alcoholic fatty liver disease (NAFLD) (n=62),
      and compared to healthy controls. RESULTS: In CCl(4)-treated rats, mean systemic
      VICM levels increased 31% at week 12 (176 ng/mL, P<0.001), 41.7% at weeks 16 (190
      ng/mL, P<0.001), 49.2% at weeks 20 (200 ng/ml, P<0.001), compared to controls
      (134 ng/mL). VICM levels correlated with total hepatic collagen determined by
      Sirius red staining of rat livers (r=0.75, P<0.05). In the HCV cohort, when
      stratified according to the METAVIR F score, VICM levels were 63% higher in F0
      (632 ng/mL +/-75, p<0.05), 54% in F1 (597 ng/mL +/-41.3, p<0.05) and 62% in F2
      (628 ng/mL +/-59, p<0.05) all compared to controls. In the NAFLD cohort, VICM
      levels were 20.6% higher in F0 (339 +/-12 ng/mL, P<0.05), 23.8% in F1 (348 +/-12
      ng/mL, P<0.05) and 28.8% in F2 (362 +/-25 P<0.05). CONCLUSION: We demonstrated
      increased serological levels of citrullinated and MMP degraded vimentin in an
      animal model of liver fibrosis and in early fibrosis associated with HCV and
      NAFLD patients. These data suggest that citrullinated and MMP degraded proteins
      are also present in liver fibrosis.

PMID- 23145209
TI  - Soluble heparin-binding EGF-like growth factor (HB-EGF) detected by newly
      developed immuno-PCR method is a clear-cut serological biomarker for ovarian
      cancer.
AB  - Heparin-binding EGF-like growth factor (HB-EGF) is a member of the EGF family of
      growth factors that bind to and activate the EGF receptor. HB-EGF is synthesized
      as a membrane-anchored protein (proHB-EGF), and then proteolytically cleaved,
      resulting in the mitogenically active soluble form. HB-EGF plays pivotal roles in
      pathophysiological processes such as development and cell proliferation. In this
      study, we developed an immuno-PCR system for the determination of soluble HB-EGF
      concentrations in human serum. Utilizing a monoclonal antibody with neutralizing
      activity against HB-EGF as a capture antibody resulted in increasing selectivity
      for an active form of HB-EGF in serum, and immuno-PCR system improved its
      sensitivity compared to the currently available methods. As a result of
      measurement of HB-EGF in 20 ovarian cancer patients and 20 healthy volunteers,
      ovarian cancer patients showed significantly higher concentrations than healthy
      volunteers (P< 0.05), which indicates that soluble HB-EGF detected by newly
      developed immuno-PCR system can be useful serological biomarkers such as a
      diagnostic biomarker for ovarian cancer, and a predictive and pharmacodynamic
      biomarker for anti-HB-EGF targeted therapies under development.

PMID- 23145210
TI  - Extinction bursts in rats trained to self-administer nicotine or food in 1-h
      daily sessions.
AB  - Extinction bursts are characterized by a temporary increase in responding when
      drug access is withheld from rats trained to self-administer drugs of abuse. Thus
      far, one study has examined extinction bursts for nicotine self-administration
      using a 23-h access paradigm [1]. Here we examined extinction bursts using
      previously published and unpublished data in which rats were trained to self
      administer nicotine (0.03mg/kg/infusion) or food pellets (as a comparator) in 1-h
      sessions under an FR5 schedule of reinforcement followed by 1-h extinction
      sessions. Analysis of response rates during nicotine self-administration (NSA)
      was indicative of a loading phase, as response rates were significantly higher at
      the beginning of the session, which was not observed for food self
      administration. At the start of extinction for both food and nicotine, although
      sessional response rates did not increase, there was an increase in response rate
      during the first 5-min of the first extinction session relative to self
      administration. This transient extinction burst following nicotine was observed
      in a minority of subjects and correlated with the number of nicotine infusions
      obtained during self-administration. This transient extinction burst following
      food was observed in all subjects. Nicotine and food produce more transient
      extinction bursts compared to other drugs of abuse and only for a minority of
      animals in the case of nicotine. This study supports the presence of a loading
      phase in rats trained to self-administer nicotine in 1-r daily sessions and the
      presence of a transient extinction burst.

PMID- 23145211
TI  - Inactivation of AR and Notch-1 signaling by miR-34a attenuates prostate cancer
      aggressiveness.
AB  - Prostate cancer (PCa) is the second leading cause of cancer related death in men
      in the United States, suggesting that novel molecular targets as well as the
      development of agents that could deregulate such targets would become newer
      therapeutic approach for the treatment of castrate resistant prostate cancer
      (CRPC) especially the metastatic CRPC (mCRPC). In search for novel targets,
      microRNAs (miRNAs) are becoming an emerging area because miRNAs function as
      regulators of gene expression in human cancers including PCa. Previous studies
      from our laboratory have shown that the expression of miR-34a is significantly
      down-regulated in human PCa specimens consistent with PCa cell lines with
      aggressive characteristics, and that the silencing of miR-34a expression was in
      part due to hypermethylation of its promoter. There are several genes that are
      direct targets of miR-34a, and in the current study we investigated the cellular
      consequence of miR-34a over-expression and under-expression in the regulation of
      androgen receptor (AR) and Notch-1 in PCa cells. We found that over-expression of
      miR-34a led to reduced expression of AR, PSA and Notch-1. We also found that over
      expression of miR-34a significantly inhibited the growth of PCa cells. Moreover,
      over-expression of miR-34a resulted in decreased self-renewal capacity of PCa
      cells, and conversely inactivation of miR-34a led to increased self-renewal
      capacity, which is an indication of tumor cell aggressiveness. These findings
      suggest that the loss of miR-34a is directly linked with up-regulation of AR and
      Notch-1 both of which are highly expressed in PCa, and thus finding innovative
      approaches by which miR-34a expression could be up-regulated will have a huge
      impact on the treatment of PCa especially for the treatment of mCRPC.

PMID- 23145212
TI  - No serological evidence for a role of HHV-6 infection in chronic fatigue
      syndrome.
AB  - Human herpesvirus 6A (HHV-6A) and human herpesvirus 6B (HHV-6B) are associated
      with a variety of conditions including rash, fever, and encephalitis and may play
      a role in several neurological diseases. Here luciferase immunoprecipitation
      systems (LIPS) was used to develop HHV-6 serologic diagnostic tests using
      antigens encoded by the U11 gene from HHV-6A (p100) and HHV-6B (p101). Analysis
      of the antibody responses against Renilla luciferase fusions with different HHV
      6B p101 fragments identified an antigenic fragment (amino acids 389 to 858) that
      demonstrated ~86% seropositivity in serum samples from healthy US blood donors.
      Additional experiments detected a HHV-6A antigenic fragment (amino acids 751-870)
      that showed ~48% antibody seropositivity in samples from Mali, Africa, a known
      HHV-6A endemic region. In contrast to the high levels of HHV-6A immunoreactivity
      seen in the African samples, testing of US blood donors with the HHV-6A p100
      antigenic fragment revealed little immunoreactivity. To potentially explore the
      role of HHV-6 infection in human disease, a blinded cohort of controls (n=59) and
      chronic fatigue syndrome (CFS) patients (n=72) from the US was examined for serum
      antibodies. While only a few of the controls and CFS patients showed high level
      immunoreactivity with HHV-6A, a majority of both the controls and CFS patients
      showed significant immunoreactivity with HHV-6B. However, no statistically
      significant differences in antibody levels or frequency of HHV-6A or HHV-6B
      infection were detected between the controls and CFS patients. These findings
      highlight the utility of LIPS for exploring the seroepidemiology of HHV-6A and
      HHV-6B infection, but suggest that these viruses are unlikely to play a role in
      the pathogenesis of CFS.

PMID- 23145213
TI  - High risk HPV DNA subtypes and E6/E7 mRNA expression in a cohort of colposcopy
      patients from Northern Italy with high-grade histologically verified cervical
      lesions.
AB  - To evaluate the prevalence of HPV DNA genotypes in women diagnosed with cervical
      intraepithelial neoplasia grade 2 or greater (CIN 2+), together with the
      detection of mRNA transcripts from HPV 16/18/31/33/45. In 1113 women referred to
      our colposcopy unit for abnormal cytology, colposcopic assessment was followed by
      histologic examination for final diagnosis and by presence of HPV DNA and E6/E7
      mRNA transcripts. A total of 134 CIN 2+ cases were identified. Out of the 134
      women with CIN 2+ cervical lesions, 115 cases (85.8%) tested positive by PCR to
      HR HPV DNA types, and 19 (14.2%) were HR HPV DNA negative. 68 cases (50.7%) were
      positive for HPV DNA 16/18/31/33/45 and of them 50 cases were E6/E7 positive, and
      18 were E6/E7 negative. 47 cases (35.1%) were positive for high risk types other
      than 16/18/31/33/45. HPV 16 is the most frequent genotype found in histologically
      confirmed high grade cervical lesions in our series; HPV 31 is the second most
      frequent type, contributing significantly to the proportion of women with CIN 2+
      lesions in our population and shows a higher prevalence than HPV 18. Out of the
      979 women with lesions less than CIN 2, 588 cases tested positive by PCR to high
      risk HPV DNA types (60.1%), and 98 cases were E6/E7 positive from HPV
      16/18/31/33/45 (10.1%). Although HPV DNA and mRNA negative results should be
      evaluated with caution, since they could represent "false negatives", high risk
      HPV DNA positivity should be assessed carefully with colposcopy before performing
      excisional treatments, particularly in adolescents but also in patients who want
      child, since they may reflect transient situations.

PMID- 23145214
TI  - The Measurement to Understand Reclassification of Disease of Cabarrus/Kannapolis
      (MURDOCK) Study Community Registry and Biorepository.
AB  - Current understanding of chronic diseases is based on crude clinical
      characterization, imaging studies, and laboratory testing that has evolved over
      decades. The Measurement to Understand Reclassification of Disease of
      Cabarrus/Kannapolis (MURDOCK) Study is a multi-tiered, longitudinal study
      designed to enable classification of chronic diseases using clinically annotated
      biospecimen collections, -omic technologies, electronic health records, and
      standard epidemiological methods. We expect that detailed molecular
      classification will improve mechanistic understanding of chronic diseases,
      augmenting discovery and testing of new treatments, and allowing refined
      selection of prevention and treatment strategies. The MURDOCK Study Community
      Registry and Biorepository will serve as a bridge for validation of initial
      exploratory studies, a platform for future prospective studies in targeted
      populations, and a resource of both data (analytical and clinical) and samples
      for cross-registry meta-analyses and comparative population studies.
      Participation of local health care providers and the Cabarrus County/Kannapolis,
      NC, community will facilitate future medical research and provide the opportunity
      to educate and inform the public about genomic research, actively engaging them
      in shaping the future of medical discovery and treatment of chronic diseases. We
      present the rationale and study design for the MURDOCK Community Registry and
      Biorepository and baseline characteristics of the first 6000 participants.

PMID- 23145215
TI  - Truncated Nucleosides as A(3) Adenosine Receptor Ligands: Combined 2-Arylethynyl
      and Bicyclohexane Substitutions.
AB  - C2-Arylethynyladenosine-5'-N-methyluronamides containing a bicyclo[3.1.0]hexane
      ((N)-methanocarba) ring are selective A(3) adenosine receptor (AR) agonists.
      Similar 4'-truncated C2-arylethynyl-(N)-methanocarba nucleosides containing alkyl
      or alkylaryl groups at the N(6) position were low-efficacy agonists or
      antagonists of the human A(3)AR with high selectivity. Higher hA(3)AR affinity
      was associated with N(6)-methyl and ethyl (K(i) 3-6 nM), than with N(6)-arylalkyl
      groups. However, combined C2-phenylethynyl and N(6)-2-phenylethyl substitutions
      in selective antagonist 15 provided a K(i) of 20 nM. Differences between 4'
      truncated and nontruncated analogues of extended C2-p-biphenylethynyl
      substitution suggested a ligand reorientation in AR binding, dominated by bulky
      N(6) groups in analogues lacking a stabilizing 5'-uronamide moiety. Thus, 4'
      truncation of C2-arylethynyl-(N)-methanocarba adenosine derivatives is compatible
      with general preservation of A(3)AR selectivity, especially with small N(6)
      groups, but reduced efficacy in A(3)AR-induced inhibition of adenylate cyclase.

PMID- 23145216
TI  - Weakly Antiferromagentic Coupling Via Superexchange Interaction Between Mn(II)
      Mn(II) Atoms: A QM/MM Study of the Active Site of Human Cytosolic X-Propyl
      Aminopeptidase P.
AB  - We investigate the dinuclear manganese, Mn(II)-Mn(II), active site of human
      cytosolic X-propyl aminopeptidase (XPNPEP1) employing the QM/MM method. The
      optimized structure supports two manganese atoms at the active site and excludes
      the possibility of a single Mn(II) atom or other combination of divalent metal
      ions: Ca(II), Fe(II), Mg(II). A broken symmetry solution verifies an
      antiferromagnetically coupled state between the Mn(II)-Mn(II) pair, which is the
      ground state. From the energy difference between the high spin state (HS) and the
      broken symmetry state (BS), we estimate the exchange coupling constant, J, to be
      5.15 cm(-1). Also, we observe multiple bridges (p orbitals) from solvent and two
      carboxylate linking to the Mn(II)-Mn(II), which leads to the weakly
      antiferromagnetic interaction of d(5)-d(5) electrons through superexchange
      coupling.

PMID- 23145217
TI  - Increasing the perceptual salience of relationships in parallel coordinate plots.
AB  - We present three extensions to parallel coordinates that increase the perceptual
      salience of relationships between axes in multivariate data sets: (1) luminance
      modulation maintains the ability to preattentively detect patterns in the
      presence of overplotting, (2) adding a one-vs.-all variable display highlights
      relationships between one variable and all others, and (3) adding a scatter plot
      within the parallel-coordinates display preattentively highlights clusters and
      spatial layouts without strongly interfering with the parallel-coordinates
      display. These techniques can be combined with one another and with existing
      extensions to parallel coordinates, and two of them generalize beyond cases with
      known-important axes. We applied these techniques to two real-world data sets
      (relativistic heavy-ion collision hydrodynamics and weather observations with
      statistical principal component analysis) as well as the popular car data set. We
      present relationships discovered in the data sets using these methods.

PMID- 23145219
TI  - The viewing-from-above bias and the silhouette illusion.
AB  - The silhouette illusion published online a number of years ago by the Japanese
      Flash designer Nobuyuki Kayahara has received substantial attention from the
      online community. One feature that seems to make it interesting is an apparent
      rotational bias: Observers see it spinning more often clockwise than counter
      clockwise. Here, we show that this rotational bias is in fact due to the visual
      system's preference for viewpoints from above rather than from below.

PMID- 23145218
TI  - Identification of everyday objects on the basis of Gaborized outline versions.
AB  - Using outlines derived from a widely used set of line drawings, we created
      stimuli geared towards the investigation of contour integration and texture
      segmentation using shapes of everyday objects. Each stimulus consisted of Gabor
      elements positioned and oriented curvilinearly along the outline of an object,
      embedded within a larger Gabor array of homogeneous density. We created six
      versions of the resulting Gaborized outline stimuli by varying the orientations
      of elements inside and outside the outline. Data from two experiments, in which
      participants attempted to identify the objects in the stimuli, provide norms for
      identifiability and name agreement, and show differences in identifiability
      between stimulus versions. While there was substantial variability between the
      individual objects in our stimulus set, further analyses suggest a number of
      stimulus properties which are generally predictive of identification performance.
      The stimuli and the accompanying normative data, both available on our website
      (http://www.gestaltrevision.be/sources/gaboroutlines), provide a useful tool to
      further investigate contour integration and texture segmentation in both normal
      and clinical populations, especially when top-down influences on these processes,
      such as the role of prior knowledge of familiar objects, are of main interest.

PMID- 23145220
TI  - Infants and toddlers show enlarged visual sensitivity to nonaccidental compared
      with metric shape changes.
AB  - Some shape changes are more important for object perception than others. We used
      a habituation paradigm to measure visual sensitivity to a nonaccidental shape
      change-that is, the transformation of a trapezium into a triangle and vice versa
      and a metric shape change-that is, changing the aspect ratio of the shapes. Our
      data show that an enhanced perceptual sensitivity to nonaccidental changes is
      already present in infancy and remains stable into toddlerhood. We have thus
      established an example of how early visual perception deviates from the null
      hypothesis of representing similarity as a function of physical overlap between
      shapes, and does so in agreement with more cognitive, categorical demands.

PMID- 23145221
TI  - The shading cue in context.
AB  - The shading cue is supposed to be a major factor in monocular stereopsis.
      However, the hypothesis is hardly corroborated by available data. For instance,
      the conventional stimulus used in perception research, which involves a circular
      disk with monotonic luminance gradient on a uniform surround, is theoretically
      'explained' by any quadric surface, including spherical caps or cups (the
      conventional response categories), cylindrical ruts or ridges, and saddle
      surfaces. Whereas cylindrical ruts or ridges are reported when the outline is
      changed from circular to square, saddle surfaces are never reported. We introduce
      a method that allows us to differentiate between such possible responses. We
      report observations on a number of variations of the conventional stimulus,
      including variations of shape and quality of the boundary, and contexts that
      allow the observer to infer illumination direction. We find strong and expected
      influences of outline shape, but, perhaps surprisingly, we fail to find any
      influence of context, and only partial influence of outline quality. Moreover, we
      report appreciable differences within the generic population. We trace some of
      the idiosyncrasies (as compared to shape from shading algorithms) of the human
      observer to generic properties of the environment, in particular the fact that
      many objects are limited in size and elliptically convex over most of their
      boundaries.

PMID- 23145222
TI  - Altered spatial frequency content in paintings by artists with schizophrenia.
AB  - While it is difficult to imagine the way someone with mental illness perceives
      the world, paintings produced by mental illness sufferers with artistic talents
      offer a hint of this experience. Here we analyze these images in terms of
      statistics related to low-level visual processing. It is known that art in
      general possesses regular spatial frequency amplitude spectra, probably due to
      factors including luminance compression, approximation of natural scene spatial
      statistics, media, and aesthetics. Whatever the contributions of those factors
      may be, would the same ones apply for artists with schizophrenia? We find that
      spatial frequency content in paintings by five artists with schizophrenia or
      schizoaffective disorder is significantly different from that found in a large
      sample of art by painters without schizophrenia, while other basic spatial and
      intensity statistics are not different for the two groups. In particular,
      amplitude spectrum slopes are significantly steeper for paintings by artists with
      schizophrenia. A separate study of the works of one artist diagnosed with
      schizoaffective disorder confirmed these findings and showed no effect of
      medication type on amplitude spectrum slope. We suggest that these results
      support the notion that people with schizophrenia show decreased contrast
      sensitivity at low spatial frequencies. If people with schizophrenia cannot
      perceive low frequencies at the same level of contrast as that at which healthy
      individuals can, it follows that on average they will portray such components
      with higher contrast, resulting in steeper spectra.

PMID- 23145223
TI  - A mismatch in the human realism of face and voice produces an uncanny valley.
AB  - The uncanny valley has become synonymous with the uneasy feeling of viewing an
      animated character or robot that looks imperfectly human. Although previous
      uncanny valley experiments have focused on relations among a character's visual
      elements, the current experiment examines whether a mismatch in the human realism
      of a character's face and voice causes it to be evaluated as eerie. The results
      support this hypothesis.

PMID- 23145224
TI  - Object knowledge modulates colour appearance.
AB  - We investigated the memory colour effect for colour diagnostic artificial
      objects. Since knowledge about these objects and their colours has been learned
      in everyday life, these stimuli allow the investigation of the influence of
      acquired object knowledge on colour appearance. These investigations are relevant
      for questions about how object and colour information in high-level vision
      interact as well as for research about the influence of learning and experience
      on perception in general. In order to identify suitable artificial objects, we
      developed a reaction time paradigm that measures (subjective) colour
      diagnosticity. In the main experiment, participants adjusted sixteen such objects
      to their typical colour as well as to grey. If the achromatic object appears in
      its typical colour, then participants should adjust it to the opponent colour in
      order to subjectively perceive it as grey. We found that knowledge about the
      typical colour influences the colour appearance of artificial objects. This
      effect was particularly strong along the daylight axis.

PMID- 23145225
TI  - Alternation frequency thresholds for stereopsis as a technique for exploring
      stereoscopic difficulties.
AB  - When stereoscopic images are presented alternately to the two eyes, stereopsis
      occurs at F >= 1 Hz full-cycle frequencies for very simple stimuli, and F >= 3 Hz
      full-cycle frequencies for random-dot stereograms (eg Ludwig I, Pieper W, Lachnit
      H, 2007 "Temporal integration of monocular images separated in time: stereopsis,
      stereoacuity, and binocular luster" Perception & Psychophysics69 92-102). Using
      twenty different stereograms presented through liquid crystal shutters, we
      studied the transition to stereopsis with fifteen subjects. The onset of
      stereopsis was observed during a stepwise increase of the alternation frequency,
      and its disappearance was observed during a stepwise decrease in frequency. The
      lowest F values (around 2.5 Hz) were observed with stimuli involving two to four
      simple disjoint elements (circles, arcs, rectangles). Higher F values were needed
      for stimuli containing slanted elements or curved surfaces (about 1 Hz
      increment), overlapping elements at two different depths (about 2.5 Hz
      increment), or camouflaged overlapping surfaces (> 7 Hz increment). A textured
      cylindrical surface with a horizontal axis appeared easier to interpret (5.7 Hz)
      than a pair of slanted segments separated in depth but forming a cross in
      projection (8 Hz). Training effects were minimal, and F usually increased as
      disparities were reduced. The hierarchy of difficulties revealed in the study may
      shed light on various problems that the brain needs to solve during stereoscopic
      interpretation. During the construction of the three-dimensional percept, the
      loss of information due to natural decay of the stimuli traces must be
      compensated by refreshes of visual input. In the discussion an attempt is made to
      link our results with recent advances in the comprehension of visual scene
      memory.

PMID- 23145226
TI  - Applying the Helmholtz illusion to fashion: horizontal stripes won't make you
      look fatter.
AB  - A square composed of horizontal lines appears taller and narrower than an
      identical square made up of vertical lines. Reporting this illusion, Hermann von
      Helmholtz noted that such illusions, in which filled space seems to be larger
      than unfilled space, were common in everyday life, adding the observation that
      ladies' frocks with horizontal stripes make the figure look taller. As this
      assertion runs counter to modern popular belief, we have investigated whether
      vertical or horizontal stripes on clothing should make the wearer appear taller
      or fatter. We find that a rectangle of vertical stripes needs to be extended by
      7.1% vertically to match the height of a square of horizontal stripes and that a
      rectangle of horizontal stripes must be made 4.5% wider than a square of vertical
      stripes to match its perceived width. This illusion holds when the horizontal or
      vertical lines are on the dress of a line drawing of a woman. We have examined
      the claim that these effects apply only for 2-dimensional figures in an
      experiment with 3-D cylinders and find no support for the notion that horizontal
      lines would be 'fattening' on clothes. Significantly, the illusion persists when
      the horizontal or vertical lines are on pictures of a real half-body mannequin
      viewed stereoscopically. All the evidence supports Helmholtz's original
      assertion.

PMID- 23145227
TI  - Measuring 3D point configurations in pictorial space.
AB  - We propose a novel method to probe the depth structure of the pictorial space
      evoked by paintings. The method involves an exocentric pointing paradigm that
      allows one to find the slope of the geodesic connection between any pair of
      points in pictorial space. Since the locations of the points in the picture plane
      are known, this immediately yields the depth difference between the points. A set
      of depth differences between all pairs of points from an N-point (N > 2)
      configuration then yields the configuration in depth up to an arbitrary depth
      offset. Since an N-point configuration implies N(N-1) (ordered) pairs, the number
      of observations typically far exceeds the number of inferred depths. This yields
      a powerful check on the geometrical consistency of the results. We report that
      the remaining inconsistencies are fully accounted for by the spread encountered
      in repeated observations. This implies that the concept of 'pictorial space'
      indeed has an empirical significance. The method is analyzed and empirically
      verified in considerable detail. We report large quantitative interobserver
      differences, though the results of all observers agree modulo a certain affine
      transformation that describes the basic cue ambiguities. This is expected on the
      basis of a formal analysis of monocular optical structure. The method will prove
      useful in a variety of potential applications.

PMID- 23145228
TI  - Surprise leads to noisier perceptual decisions.
AB  - Surprising events in the environment can impair task performance. This might be
      due to complete distraction, leading to lapses during which performance is
      reduced to guessing. Alternatively, unpredictability might cause a graded
      withdrawal of perceptual resources from the task at hand and thereby reduce
      sensitivity. Here we attempt to distinguish between these two mechanisms.
      Listeners performed a novel auditory pitch-duration discrimination, where
      stimulus loudness changed occasionally and incidentally to the task. Responses
      were slower and less accurate in the surprising condition, where loudness changed
      unpredictably, than in the predictable condition, where the loudness was held
      constant. By explicitly modelling both lapses and changes in sensitivity, we
      found that unpredictable changes diminished sensitivity but did not increase the
      rate of lapses. These findings suggest that background environmental uncertainty
      can disrupt goal-directed behaviour. This graded processing strategy might be
      adaptive in potentially threatening contexts, and reflect a flexible system for
      automatic allocation of perceptual resources.

PMID- 23145230
TI  - Paradoxical perception of surfaces in the Shepard tabletop illusion.
AB  - The Shepard tabletop illusion, consisting of different perspective embeddings of
      two identical parallelograms as tabletops, affords a profound difference in their
      perceived surface shapes. My analysis reveals three further paradoxical aspects
      of this illusion, in addition to its susceptibility to the 'inverse perspective
      illusion' of the implied orthographic perspective of the table images. These
      novel aspects of the illusion are: a paradoxical slant of the tabletops, a
      paradoxical lack of perceived depth, and a paradoxical distortion of the length
      of the rear legs. The construction of the illusion resembles scenes found in
      ancient Chinese scroll paintings, and an analysis of the source of the third
      effect shows that the interpretation in terms of surfaces can account for the
      difference in treatment of the filled-in versus open forms in the Chinese
      painting from more than 1000 years ago.

PMID- 23145229
TI  - Development of differential sensitivity for shape changes resulting from linear
      and nonlinear planar transformations.
AB  - A shape bias for extending names to objects that look visually similar has been
      commonly accepted but it is hard to define which kind of shape dissimilarities
      are diagnostic for the identity of an object. Here, we present a transformational
      approach to describe shape differences that can incorporate many significant
      shape features. We introduce two kinds of transformations: one kind concerns
      linear transformations of the image plane (affine transformations), generally
      limiting shape variations within the borders of basic-level categories; the other
      kind concerns nonlinear continuous transformations of the image plane
      (topological transformations), allowing all kinds of shape variation crossing and
      not crossing the borders of basic-level categories. We administered stimulus
      pairs differing in these shape transformations to children of 3 years to 7 years
      old in a delayed match-to-sample task. With increasing age, especially between 5
      years and 6 years, children became more sensitive to the topological deformations
      that are relevant for between-category distinctions, indicating that acquired
      categorical knowledge in early years induces perceptual learning of the relevant
      generic shape differences between categories.

PMID- 23145231
TI  - Does cognitive perception have access to brief temporal events?
AB  - To determine whether conscious perception has access to brief temporal event, we
      asked subjects in an odd-man out paradigm to determine which of the four Gaussian
      blobs was flickering asynchronously in time. We measure synchrony thresholds as a
      function of the base temporal frequency for spatially scaled stimuli in foveal
      and peripheral vision. The results are consistent with a time delay of around 67
      milliseconds (ms) for foveal vision and 91 ms for peripheral vision. We conclude
      that conscious perception has access to only relatively long (~67 ms) time
      events.

PMID- 23145232
TI  - You do not talk about Fight Club if you do not notice Fight Club: Inattentional
      blindness for a simulated real-world assault.
AB  - Inattentional blindness-the failure to see visible and otherwise salient events
      when one is paying attention to something else-has been proposed as an
      explanation for various real-world events. In one such event, a Boston police
      officer chasing a suspect ran past a brutal assault and was prosecuted for
      perjury when he claimed not to have seen it. However, there have been no
      experimental studies of inattentional blindness in real-world conditions. We
      simulated the Boston incident by having subjects run after a confederate along a
      route near which three other confederates staged a fight. At night only 35% of
      subjects noticed the fight; during the day 56% noticed. We manipulated the
      attentional load on the subjects and found that increasing the load significantly
      decreased noticing. These results provide evidence that inattentional blindness
      can occur during real-world situations, including the Boston case.

PMID- 23145233
TI  - Nonrigid illusory motion in depth induced by translational motion of static
      images.
AB  - A new nonrigid motion illusion is presented based on patterns of aligned
      nonparallel line segments undergoing apparent motion. The illusory effect can be
      explained by the mismatch in local orientation segments that signals local
      rotational motion contradictory to the global translational motion.

PMID- 23145235
TI  - The hollow-face illusion in infancy: do infants see a screen based rotating
      hollow mask as hollow?
AB  - We investigated whether infants experience the hollow-face illusion using a
      screen-based presentation of a rotating hollow mask. In experiment 1 we examined
      preferential looking between rotating convex and concave faces. Adults looked
      more at the concave-illusory convex-face which appears to counter rotate. Infants
      of 7- to 8-month-old infants preferred the convex face, and 5- to 6-month-olds
      showed no preference. While older infants discriminate, their preference differed
      from that of adults possibly because they don't experience the illusion or
      counter rotation. In experiment 2 we tested preference in 7- to 8-month-olds for
      angled convex and concave static faces both before and after habituation to the
      stimuli shown in experiment 1. The infants showed a novelty preference for the
      static shape opposite to the habituation stimulus, together with a general
      preference for the static convex face. This shows that they discriminate between
      convex and concave faces and that habituation to either transfers across a change
      in view. Seven- to eight-month-olds have been shown to discriminate direction of
      rigid rotation on the basis of perspective changes. Our results suggest that
      this, perhaps together with a weaker bias to perceive faces as convex, allows
      these infants to see the screen-based hollow face as hollow even though adults
      perceive it as convex.

PMID- 23145234
TI  - A reevaluation of achromatic spatio-temporal vision: Nonoriented filters are
      monocular, they adapt, and can be used for decision making at high flicker
      speeds.
AB  - Masking, adaptation, and summation paradigms have been used to investigate the
      characteristics of early spatio-temporal vision. Each has been taken to provide
      evidence for (i) oriented and (ii) nonoriented spatial-filtering mechanisms.
      However, subsequent findings suggest that the evidence for nonoriented mechanisms
      has been misinterpreted: those experiments might have revealed the
      characteristics of suppression (eg, gain control), not excitation, or merely the
      isotropic subunits of the oriented detecting mechanisms. To shed light on this,
      we used all three paradigms to focus on the 'high-speed' corner of spatio
      temporal vision (low spatial frequency, high temporal frequency), where cross
      oriented achromatic effects are greatest. We used flickering Gabor patches as
      targets and a 2IFC procedure for monocular, binocular, and dichoptic stimulus
      presentations. To account for our results, we devised a simple model involving an
      isotropic monocular filter-stage feeding orientation-tuned binocular filters.
      Both filter stages are adaptable, and their outputs are available to the decision
      stage following nonlinear contrast transduction. However, the monocular isotropic
      filters (i) adapt only to high-speed stimuli-consistent with a magnocellular
      subcortical substrate-and (ii) benefit decision making only for high-speed
      stimuli (ie, isotropic monocular outputs are available only for high-speed
      stimuli). According to this model, the visual processes revealed by masking,
      adaptation, and summation are related but not identical.

PMID- 23145236
TI  - Stream/bounce event perception reveals a temporal limit of motion correspondence
      based on surface feature over space and time.
AB  - We examined how stream/bounce event perception is affected by motion
      correspondence based on the surface features of moving objects passing behind an
      occlusion. In the stream/bounce display two identical objects moving across each
      other in a two-dimensional display can be perceived as either streaming through
      or bouncing off each other at coincidence. Here, surface features such as colour
      (Experiments 1 and 2) or luminance (Experiment 3) were switched between the two
      objects at coincidence. The moment of coincidence was invisible to observers due
      to an occluder. Additionally, the presentation of the moving objects was
      manipulated in duration after the feature switch at coincidence. The results
      revealed that a postcoincidence duration of approximately 200 ms was required for
      the visual system to stabilize judgments of stream/bounce events by determining
      motion correspondence between the objects across the occlusion on the basis of
      the surface feature. The critical duration was similar across motion speeds of
      objects and types of surface features. Moreover, controls (Experiments 4a-4c)
      showed that cognitive bias based on feature (colour/luminance) congruency across
      the occlusion could not fully account for the effects of surface features on the
      stream/bounce judgments. We discuss the roles of motion correspondence, visual
      feature processing, and attentive tracking in the stream/bounce judgments.

PMID- 23145237
TI  - Sensitivity to first- and second-order drifting gratings in 3-month-old infants.
AB  - In two experiments, we investigated 3-month-old infants' sensitivity to first-
      and second-order drifting gratings. In Experiment 1 we used forced-choice
      preferential looking with drifting versus stationary gratings to estimate depth
      modulation thresholds for 3-month-old infants and a similar task for a comparison
      group of adults. Thresholds for infants were more adult-like for second-order
      than first-order gratings. In Experiment 2, 3-month-olds dishabituated to a
      change in first-order orientation, but not to a change in direction of first- or
      second-order motion. Hence, results from Experiment 1 were likely driven by the
      perception of flicker rather than motion. Thus, infants' sensitivity to uniform
      motion is slow to develop and appears to be driven initially by flicker-sensitive
      mechanisms. The underlying mechanisms have more mature tuning for second-order
      than for first-order information.

PMID- 23145239
TI  - Disambiguation of mental rotation by spatial frames of reference.
AB  - Previous research has shown that our ability to imagine object rotations is
      limited and associated with spatial reference frames; performance is poor unless
      the axis of rotation is aligned with the object-intrinsic frame or with the
      environmental frame. Here, we report an active effect of these reference frames
      on the process of mental rotation: they can disambiguate object rotations when
      the axis of rotation is ambiguous. Using novel mental rotation stimuli, in which
      the rotational axes between pairs of objects can be defined with respect to
      multiple frames of reference, we demonstrate that the vertical axis is
      preferentially used for imagined object rotations over the object-intrinsic axis
      for an efficient minimum rotation. In contrast, the object-intrinsic axis can
      play a decisive role when the vertical axis is absent as a way of resolving the
      ambiguity of rotational motion. When interpreted in conjunction with recent
      advances in the Bayesian framework for motion perception, our results suggest
      that these spatial frames of reference are incorporated into an internal model of
      object rotations, thereby shaping our ability to imagine the transformation of an
      object's spatial structure.

PMID- 23145238
TI  - Faces in the mist: illusory face and letter detection.
AB  - We report three behavioral experiments on the spatial characteristics evoking
      illusory face and letter detection. False detections made to pure noise images
      were analyzed using a modified reverse correlation method in which hundreds of
      observers rated a modest number of noise images (480) during a single session.
      This method was originally developed for brain imaging research, and has been
      used in a number of fMRI publications, but this is the first report of the
      behavioral classification images. In Experiment 1 illusory face detection
      occurred in response to scattered dark patches throughout the images, with a bias
      to the left visual field. This occurred despite the use of a fixation cross and
      expectations that faces would be centered. In contrast, illusory letter detection
      (Experiment 2) occurred in response to centrally positioned dark patches.
      Experiment 3 included an oval in all displays to spatially constrain illusory
      face detection. With the addition of this oval the classification image revealed
      an eyes/nose/mouth pattern. These results suggest that face detection is
      triggered by a minimal face-like pattern even when these features are not
      centered in visual focus.

PMID- 23145240
TI  - Eye contricks.
AB  - Pictorial images are icons as well as eye-cons: they provide distillations of
      objects or ideas into simpler shapes. They create the impression of representing
      that which cannot be presented. Even at the level of the photograph, the links
      between icon and object are tenuous. The dimensions of depth and motion are
      missing from icons, and these alone introduce all manner of potential
      ambiguities. The history of art can be considered as exploring the missing link
      between icon and object. Eye-cons can also be illusions-tricks of vision so that
      what is seen does not necessarily correspond to what is physically presented.
      Pictorial images can be spatialised or stylised; spatialised images generally
      share some of the projective characteristics of the object represented. Written
      words are also icons, but they do not resemble the objects they represent-they
      are stylised or conventional. Icons as stylised words and spatialised images were
      set in delightful opposition by Rene Magritte in a series of pipe paintings, and
      this theme is here alluded to. Most of visual science is now concerned with icons
      two-dimensional displays on computer monitors. Is vision now the science of eye
      cons?

PMID- 23145241
TI  - San Lorenzo and the Poggendorff illusion in Ravenna.
AB  - In the Mausoleum of Galla Placidia (Ravenna, Italy), the San Lorenzo lunette
      shows two peculiar visual effects: a transparency effect of gold seen through
      gold and perceptual collinearity between two parts of a cross which are
      physically misaligned. Both effects are found within the area of the halo
      surrounding the saint's head. In this work we addressed the problem posed by the
      physical misalignment of the cross. Our hypothesis is that the physical
      misalignment went unnoticed throughout history because the artist produced a
      perceptual alignment to correct for the Poggendorff illusion. Hence, we asked
      observers to align two ends of a cross in a reproduction showing the silhouette
      of San Lorenzo's torso holding the cross. Results support our hypothesis: both
      direction and magnitude of adjustments comply with the alignment in the original
      mosaic.

PMID- 23145242
TI  - Measuring pictorial balance perception at first glance using Japanese
      calligraphy.
AB  - According to art theory, pictorial balance acts to unify picture elements into a
      cohesive composition. For asymmetrical compositions, balancing elements is
      thought to be similar to balancing mechanical weights in a framework of symmetry
      axes. Assessment of preference for balance (APB), based on the symmetry-axes
      framework suggested in Arnheim R, 1974 Art and Visual Perception: A Psychology of
      the Creative Eye (Berkeley, CA: University of California Press), successfully
      matched subject balance ratings of images of geometrical shapes over unlimited
      viewing time. We now examine pictorial balance perception of Japanese calligraphy
      during first fixation, isolated from later cognitive processes, comparing APB
      measures with results from balance-rating and comparison tasks. Results show high
      between-task correlation, but low correlation with APB. We repeated the rating
      task, expanding the image set to include five rotations of each image, comparing
      balance perception of artist and novice participant groups. Rotation has no
      effect on APB balance computation but dramatically affects balance rating,
      especially for art experts. We analyze the variety of rotation effects and
      suggest that, rather than depending on element size and position relative to
      symmetry axes, first fixation balance processing derives from global processes
      such as grouping of lines and shapes, object recognition, preference for
      horizontal and vertical elements, closure, and completion, enhanced by vertical
      symmetry.

PMID- 23145243
TI  - The effect of left-right reversal on film: Watching Kurosawa reversed.
AB  - The mirror reversal of an image is subtly different from the original. Often such
      change goes unnoticed in pictures, although it can affect preference. For the
      first time we studied the effect of mirror reversal of feature films. People
      watched Yojimbo or Sanjuro in a cinema, both classic films by Akira Kurosawa.
      They knew that this was a study and filled out a questionnaire. On one day
      Yojimbo was shown in its original orientation, and on another day the film was
      mirror reversed. Sanjuro was shown reversed on one day and non-reversed on
      another day. Viewers did not notice the reversal, even when they had seen the
      film before and considered themselves fans of Kurosawa. We compared this with
      estimates from a survey. In addition, the question about the use of space
      (scenography) revealed that although people who had seen the film before gave
      higher ratings compared with those who had not, this was only true when the film
      was not reversed.

PMID- 23145244
TI  - Depth.
AB  - Depth is the feeling of remoteness, or separateness, that accompanies awareness
      in human modalities like vision and audition. In specific cases depths can be
      graded on an ordinal scale, or even measured quantitatively on an interval scale.
      In the case of pictorial vision this is complicated by the fact that human
      observers often appear to apply mental transformations that involve depths in
      distinct visual directions. This implies that a comparison of empirically
      determined depths between observers involves pictorial space as an integral
      entity, whereas comparing pictorial depths as such is meaningless. We describe
      the formal structure of pictorial space purely in the phenomenological domain,
      without taking recourse to the theories of optics which properly apply to
      physical space-a distinct ontological domain. We introduce a number of general
      ways to design and implement methods of geodesy in pictorial space, and discuss
      some basic problems associated with such measurements. We deal mainly with
      conceptual issues.

PMID- 23145245
TI  - Coronal streamers revealed during solar eclipses: Seeing is not believing, and
      pictures can lie.
AB  - For those fortunate enough to have personally witnessed and photographed the
      visible corona surrounding the Sun during a solar eclipse, pictures are usually a
      let down for not living up to the visual view. After 150 years of investigating
      the corona, we understand it more fully and now know this difference to be real.
      The difference stems from our inability to either see or image the true
      distribution of simultaneous brightness because of its large dynamic range (eg,
      Rodriguez, Woods, 2008 Digital Image Processing, Upper Saddle River: Pearson
      Prentice Hall). Brightness in the corona is unprecedented, as it falls by three
      orders of magnitude over a distance of only one solar radius from the Sun.

PMID- 23145246
TI  - Quicker, faster, darker: Changes in Hollywood film over 75 years.
AB  - We measured 160 English-language films released from 1935 to 2010 and found four
      changes. First, shot lengths have gotten shorter, a trend also reported by
      others. Second, contemporary films have more motion and movement than earlier
      films. Third, in contemporary films shorter shots also have proportionately more
      motion than longer shots, whereas there is no such relation in older films. And
      finally films have gotten darker. That is, the mean luminance value of frames
      across the length of a film has decreased over time. We discuss psychological
      effects associated with these four changes and suggest that all four linear
      trends have a single cause: Filmmakers have incrementally tried to exercise more
      control over the attention of filmgoers. We suggest these changes are signatures
      of the evolution of popular film; they do not reflect changes in film style.

PMID- 23145247
TI  - Layers of looking.
AB  - The films that I make are part documentary, part film essay, part visual poem.
      They are created out of a series of up to 30 drawings that are animated. The
      process from research to completion takes about 2 years, and at the end of it
      there is a film and a number of drawings that can be exhibited. This paper
      emerges out of the realisation that in the different stages of making a drawing
      and a film-from planning a drawing and seeking an image as a starting point
      through to the finished film being projected onto a screen in a gallery-I am
      looking at the image in different ways. There is a close-up kind of looking when
      I am drawing and a reflective kind of looking when I step back to take stock.
      There is a way of looking at darks and lights as they are built up that is
      different from the way of looking at the lines crossing the edges of the grid
      being used to transfer an image to the drawing paper. Seeing the drawings on the
      wall of my studio is different from seeing the same drawings in a museum setting.

PMID- 23145248
TI  - New insights into ambient and focal visual fixations using an automatic
      classification algorithm.
AB  - Overt visual attention is the act of directing the eyes toward a given area.
      These eye movements are characterised by saccades and fixations. A debate
      currently surrounds the role of visual fixations. Do they all have the same role
      in the free viewing of natural scenes? Recent studies suggest that at least two
      types of visual fixations exist: focal and ambient. The former is believed to be
      used to inspect local areas accurately, whereas the latter is used to obtain the
      context of the scene. We investigated the use of an automated system to cluster
      visual fixations in two groups using four types of natural scene images. We found
      new evidence to support a focal-ambient dichotomy. Our data indicate that the
      determining factor is the saccade amplitude. The dependence on the low-level
      visual features and the time course of these two kinds of visual fixations were
      examined. Our results demonstrate that there is an interplay between both
      fixation populations and that focal fixations are more dependent on low-level
      visual features than are ambient fixations.

PMID- 23145249
TI  - Dichoptic completion, rather than binocular rivalry or binocular summation.
AB  - When one monocular image contains a red square partly occluding a green square,
      and the other monocular image is the same except that the green square is partly
      occluding the red one, the two images resemble each other's amodal completion.
      Observers typically perceive two complete squares as if the red and green
      surfaces are transparent or penetrating each other at their overlapping image
      location, which never appears yellow. With this example, we introduce dichoptic
      completion as a perception with the following characteristics. (1) Similar to
      binocular rivalry, it is evoked by dichoptic stimuli with monocular images so
      disparate that they cannot arise from physical scenes; however, (2) it occurs
      when objects inferred from one monocular image are identified with, or do not
      conflict with, objects inferred from the other; and, consequently, (3) it is a
      form of perceptual superposition, distinct from the result of binocular summation
      or rivalry.

PMID- 23145250
TI  - Arnheim's Gestalt theory of visual balance: Examining the compositional structure
      of art photographs and abstract images.
AB  - In Art and Visual Perception, Rudolf Arnheim, following on from Denman Ross's A
      Theory of Pure Design, proposed a Gestalt theory of visual composition. The
      current paper assesses a physicalist interpretation of Arnheim's theory,
      calculating an image's centre of mass (CoM). Three types of data are used: a
      large, representative collection of art photographs of recognised quality;
      croppings by experts and non-experts of photographs; and Ross and Arnheim's
      procedure of placing a frame around objects such as Arnheim's two black disks.
      Compared with control images, the CoM of art photographs was closer to an axis
      (horizontal, vertical, or diagonal), as was the case for photographic croppings.
      However, stronger, within-image, paired comparison studies, comparing art
      photographs with the CoM moved on or off an axis (the 'gamma-ramp study'), or
      comparing adjacent croppings on or off an axis (the 'spider-web study'), showed
      no support for the Arnheim-Ross theory. Finally, studies moving a frame around
      two disks, of different size, greyness, or background, did not support Arnheim's
      Gestalt theory. Although the detailed results did not support the Arnheim-Ross
      theory, several significant results were found which clearly require explanation
      by any adequate theory of the aesthetics of visual composition.

PMID- 23145251
TI  - Towards a new kind of experimental psycho-aesthetics? Reflections on the
      Parallellepipeda project.
AB  - Experimental psycho-aesthetics-the science aimed at understanding the factors
      that determine aesthetic experience-is reviewed briefly as background to describe
      the Parallellepipeda project, a cross-over project between artists and scientists
      in Leuven. In particular, I sketch how it started and developed further, with
      close interactions between the participating artists and scientists. A few
      examples of specific research projects are mentioned to illustrate the kind of
      research questions we address and the methodological approach we have taken. We
      often found an effect of providing participants with additional information, a
      difference between novice and expert participants, and a shift with increasing
      experience with an artwork, in the direction of tolerating more complexity and
      acquiring more order from it. By establishing more connections between parts of
      an artwork and more associations to the artwork, it becomes a stronger Gestalt,
      which is more easily mastered by the viewer and leads to increased appreciation.
      In the final part of the paper, I extract some general lessons from the project
      regarding a possible new way of doing psycho-aesthetics research, which is able
      to solve some of the problems of traditional experimental psycho-aesthetics (eg,
      trade-off between experimental control and ecological validity).

PMID- 23145252
TI  - The art of transparency.
AB  - Artists throughout the ages have discovered a number of techniques to depict
      transparency. With only a few exceptions, these techniques follow closely the
      properties of physical transparency. The two best known properties are X
      junctions and the luminance relations described by Metelli. X-junctions are seen
      where the contours of a transparent material cross contours of the surface
      behind; Metelli's constraints on the luminance relations between the direct and
      filtered portions of the surface specify a range of luminance values that are
      consistent with transparency. These principles have been used by artists since
      the time of ancient Egypt. However, artists also discovered that stimuli can be
      seen as transparent even when these physical constraints are not met. Ancient
      Greek artists, for example, were able to depict transparent materials in simple
      black-and-white line drawings. Artists also learned how to represent transparency
      in cases where neither X-junctions nor Metelli's constraints could apply: for
      example, where no portions of the objects behind the transparent material extend
      beyond it. Many painters convincingly portrayed transparency in these cases by
      depicting the effects the transparent medium would have on material or object
      properties. Here, we show how artists employed these and other techniques
      revealing their anticipation of current formalizations of perceived transparency,
      and we suggest new, as-yet-untested principles.

PMID- 23145253
TI  - Contemporary experimental aesthetics: State of the art technology.
AB  - The purpose of this essay is to provide the reader with a brief overview of
      several recent person-artifact-context relational models that explain the complex
      interaction of the processes that underlie an ongoing aesthetic experience with
      visual art forms. Recent progress towards a comprehensive understanding of these
      processes has been made possible in large part by experimental approaches that
      take advantage of recent advances in computer technology and electronic
      sophistication. To illustrate this point, three experimental techniques at the
      forefront of the field of experimental aesthetics are highlighted here. They
      include the investigation of viewers- body postural adjustments to depicted
      pictorial depth and movement in paintings; the use of hand-held computers known
      as personal data assistants to record audience members- on-going emotional
      reactions to live performances of dance; and the contribution of audio tour
      information to museum visitors- interaction with and aesthetic evaluation of
      sculptures and paintings. Finally, the eMotion: Mapping Museum Experience
      project, which has the potential to make a tremendous contribution to the
      understanding of the complex interaction of factors that contribute to a museum
      visitor's experience, is described.

PMID- 23145254
TI  - Cognitive mechanisms for explaining dynamics of aesthetic appreciation.
AB  - For many domains aesthetic appreciation has proven to be highly reliable.
      Evaluations of facial attractiveness, for instance, show high internal
      consistencies and impressively high inter-rater reliabilities, even across
      cultures. This indicates general mechanisms underlying such evaluations. It is,
      however, also obvious that our taste for specific objects is not always stable-in
      some realms such stability is hardly conceivable at all since aesthetic domains
      such as fashion, design, or art are inherently very dynamic. Gaining insights
      into the cognitive mechanisms that trigger and enable corresponding changes of
      aesthetic appreciation is of particular interest for psychologists as this will
      probably reveal essential mechanisms of aesthetic evaluations per se. The present
      paper develops a two-step model, dynamically adapting itself, which accounts for
      typical dynamics of aesthetic appreciation found in different research areas such
      as art history, philosophy, and psychology. The first step assumes singular
      creative sources creating and establishing innovative material towards which, in
      a second step, people adapt by integrating it into their visual habits. This
      inherently leads to dynamic changes of the beholders- aesthetic appreciation.

PMID- 23145256
TI  - Rank order scaling of pictorial depth.
AB  - We address the topic of "pictorial depth" in cases of pictures that are unlike
      photographic renderings. The most basic measure of "depth" is no doubt that of
      depth order. We establish depth order through the pairwise depth-comparison
      method, involving all pairs from a set of 49 fiducial points. The pictorial space
      for this study was evoked by a capriccio (imaginary landscape) by Francesco
      Guardi (1712-1793). In such a drawing pictorial space is suggested by the artist
      through a small set of conventional depth cues. As a result typical Western
      observers tend to agree largely in their visual awareness when looking at such
      art. We rank depths for locations that are not on a single surface and far apart
      in pictorial space. We find that observers resolve about 40 distinct depth layers
      and agree largely in this. From a previous experiment we have metrical data for
      the same observers. The rank correlations between the results are high. Perhaps
      surprisingly, we find no correlation between the number of distinct depth layers
      and the total metrical depth range. Thus, the relation between subjective
      magnitude and discrimination threshold fails to hold for pictorial depth.

PMID- 23145255
TI  - Illusory rotation of a spoked wheel.
AB  - A disk was divided into 16 stationary sectors of different grey levels that
      stepped around clockwise. When thin stationary spokes of constant mid-grey
      separated the sectors, the spokes showed robust and striking counterclockwise
      apparent motion, and when stopped, they gave a brisk clockwise motion
      aftereffect. The spokes had to match the grey of some of the sectors. We
      attribute these effects to small displacements across the thickness of the spokes
      that stimulated hard-wired motion detectors.

PMID- 23145257
TI  - Emotional effects of dynamic textures.
AB  - This study explores the effects of various spatiotemporal dynamic texture
      characteristics on human emotions. The emotional experience of auditory (eg,
      music) and haptic repetitive patterns has been studied extensively. In contrast,
      the emotional experience of visual dynamic textures is still largely unknown,
      despite their natural ubiquity and increasing use in digital media. Participants
      watched a set of dynamic textures, representing either water or various different
      media, and self-reported their emotional experience. Motion complexity was found
      to have mildly relaxing and nondominant effects. In contrast, motion change
      complexity was found to be arousing and dominant. The speed of dynamics had
      arousing, dominant, and unpleasant effects. The amplitude of dynamics was also
      regarded as unpleasant. The regularity of the dynamics over the textures' area
      was found to be uninteresting, nondominant, mildly relaxing, and mildly pleasant.
      The spatial scale of the dynamics had an unpleasant, arousing, and dominant
      effect, which was larger for textures with diverse content than for water
      textures. For water textures, the effects of spatial contrast were arousing,
      dominant, interesting, and mildly unpleasant. None of these effects were observed
      for textures of diverse content. The current findings are relevant for the design
      and synthesis of affective multimedia content and for affective scene indexing
      and retrieval.

PMID- 23145258
TI  - Pictorial depth probed through relative sizes.
AB  - In the physical environment familiar size is an effective depth cue because the
      distance from the eye to an object equals the ratio of its physical size to its
      angular extent in the visual field. Such simple geometrical relations do not
      apply to pictorial space, since the eye itself is not in pictorial space, and
      consequently the notion "distance from the eye" is meaningless. Nevertheless,
      relative size in the picture plane is often used by visual artists to suggest
      depth differences. The depth domain has no natural origin, nor a natural unit;
      thus only ratios of depth differences could have an invariant significance. We
      investigate whether the pictorial relative size cue yields coherent depth
      structures in pictorial spaces. Specifically, we measure the depth differences
      for all pairs of points in a 20-point configuration in pictorial space, and we
      account for these observations through 19 independent parameters (the depths of
      the points modulo an arbitrary offset), with no meaningful residuals. We discuss
      a simple formal framework that allows one to handle individual differences. We
      also compare the depth scale obtained by way of this method with depth scales
      obtained in totally different ways, finding generally good agreement.

PMID- 23145259
TI  - Joint effects of illumination geometry and object shape in the perception of
      surface reflectance.
AB  - Surface properties provide useful information for identifying objects and
      interacting with them. Effective utilization of this information, however,
      requires that the perception of object surface properties be relatively constant
      across changes in illumination and changes in object shape. Such constancy has
      been studied separately for changes in these factors. Here we ask whether the
      separate study of the illumination and shape effects is sufficient, by testing
      whether joint effects of illumination and shape changes can be predicted from the
      individual effects in a straightforward manner. We found large interactions
      between illumination and object shape in their effects on perceived glossiness.
      In addition, analysis of luminance histogram statistics could not account for the
      interactions.

PMID- 23145260
TI  - Putting reward in art: A tentative prediction error account of visual art.
AB  - The predictive coding model is increasingly and fruitfully used to explain a wide
      range of findings in perception. Here we discuss the potential of this model in
      explaining the mechanisms underlying aesthetic experiences. Traditionally art
      appreciation has been associated with concepts such as harmony, perceptual
      fluency, and the so-called good Gestalt. We observe that more often than not
      great artworks blatantly violate these characteristics. Using the concept of
      prediction error from the predictive coding approach, we attempt to resolve this
      contradiction. We argue that artists often destroy predictions that they have
      first carefully built up in their viewers, and thus highlight the importance of
      negative affect in aesthetic experience. However, the viewer often succeeds in
      recovering the predictable pattern, sometimes on a different level. The ensuing
      rewarding effect is derived from this transition from a state of uncertainty to a
      state of increased predictability. We illustrate our account with several example
      paintings and with a discussion of art movements and individual differences in
      preference. On a more fundamental level, our theorizing leads us to consider the
      affective implications of prediction confirmation and violation. We compare our
      proposal to other influential theories on aesthetics and explore its advantages
      and limitations.

PMID- 23145261
TI  - Effect of speed overestimation on flash-lag effect at low luminance.
AB  - When a brief flash is presented at the same location as a moving object, the
      flash is perceived to lag behind the moving object to an extent that increases
      with the speed of the object. Previous studies showed that moving objects appear
      faster at low luminance as a result of their longer motion trace. Here we examine
      whether this faster perceived motion also affects the amount of the flash lag at
      low luminance. We first verified that speed was overestimated at low luminance
      with our stimulus. We then asked subjects to align a briefly flashed dot with the
      moving target. Results showed that the flash-lag effect increased with physical
      speed at both high and low luminance, but there was no additional increase due to
      the perceived increase of speed at low luminance. We suggest that although motion
      blur contributes to perceived speed, it does not contribute to the speed
      information that influences its perceived position.

PMID- 23145262
TI  - Occlusion issues in early Renaissance art.
AB  - Early Renaissance painters innovatively attempted to depict realistic three
      dimensional scenes. A major problem was to produce the impression of overlap for
      surfaces that occlude one another in the scene but are adjoined in the picture
      plane. Much has been written about perspective in art but little about occlusion.
      Here I examine some of the strategies for depicting occlusion used by early
      Renaissance painters in relation to ecological considerations and perceptual
      research. Perceived surface overlap is often achieved by implementing the
      principle that an occluding surface occludes anything behind it, so that
      occlusion perception is enhanced by a lack of relationship of occluding contour
      to occluded contours. Some well-known figure-ground principles are also commonly
      used to stratify adjoined figures. Global factors that assist this stratification
      include the placement of figures on a ground plane, a high viewpoint, and figure
      grouping. Artists of this period seem to have differed on whether to occlude
      faces and heads, often carefully avoiding doing so. Halos were either eliminated
      selectively or placed oddly to avoid such occlusions. Finally, I argue that the
      marked intransitivity in occlusion by architecture in the paintings of Duccio can
      be related to the issue of perceptual versus cognitive influences on the visual
      impact of paintings.

PMID- 23145263
TI  - Components of aesthetic experience: aesthetic fascination, aesthetic appraisal,
      and aesthetic emotion.
AB  - In this paper aesthetic experience is defined as an experience qualitatively
      different from everyday experience and similar to other exceptional states of
      mind. Three crucial characteristics of aesthetic experience are discussed:
      fascination with an aesthetic object (high arousal and attention), appraisal of
      the symbolic reality of an object (high cognitive engagement), and a strong
      feeling of unity with the object of aesthetic fascination and aesthetic
      appraisal. In a proposed model, two parallel levels of aesthetic information
      processing are proposed. On the first level two sub-levels of narrative are
      processed, story (theme) and symbolism (deeper meanings). The second level
      includes two sub-levels, perceptual associations (implicit meanings of object's
      physical features) and detection of compositional regularities. Two sub-levels
      are defined as crucial for aesthetic experience, appraisal of symbolism and
      compositional regularities. These sub-levels require some specific cognitive and
      personality dispositions, such as expertise, creative thinking, and openness to
      experience. Finally, feedback of emotional processing is included in our model:
      appraisals of everyday emotions are specified as a matter of narrative content
      (eg, empathy with characters), whereas the aesthetic emotion is defined as an
      affective evaluation in the process of symbolism appraisal or the detection of
      compositional regularities.

PMID- 23145264
TI  - Aesthetic judgement of orientation in modern art.
AB  - When creating an artwork, the artist makes a decision regarding the orientation
      at which the work is to be hung based on their aesthetic judgement and the
      message conveyed by the piece. Is the impact or aesthetic appeal of a work
      diminished when it is hung at an incorrect orientation? To investigate this
      question, Experiment 1 asked whether naive observers can appreciate the correct
      orientation (as defined by the artist) of 40 modern artworks, some of which are
      entirely abstract. Eighteen participants were shown 40 paintings in a series of
      trials. Each trial presented all four cardinal orientations on a computer screen,
      and the participant was asked to select the orientation that was most attractive
      or meaningful. Results showed that the correct orientation was selected in 48% of
      trials on average, significantly above the 25% chance level, but well below
      perfect performance. A second experiment investigated the extent to which the 40
      paintings contained recognisable content, which may have mediated orientation
      judgements. Recognition rates varied from 0% for seven of the paintings to 100%
      for five paintings. Orientation judgements in Experiment 1 correlated
      significantly with "meaningful" content judgements in Experiment 2: 42% of the
      variance in orientation judgements in Experiment 1 was shared with recognition of
      meaningful content in Experiment 2. For the seven paintings in which no
      meaningful content at all was detected, 41% of the variance in orientation
      judgements was shared with variance in a physical measure of image content,
      Fourier amplitude spectrum slope. For some paintings, orientation judgements were
      quite consistent, despite a lack of meaningful content. The origin of these
      orientation judgements remains to be identified.

PMID- 23145265
TI  - Aesthetic preference for spatial composition in multiobject pictures.
AB  - Five experiments examined preferences for horizontal positions in multiobject
      pictures. In Experiment 1, each picture contained a fixed object and an object
      whose position could be adjusted to create the most (or least) aesthetically
      pleasing image. Observers placed the movable object closer to the fixed object
      when the objects were related than when they were unrelated (a relatedness bias)
      but almost never overlapped them (a separation bias). Experiment 2 showed that
      these results were not due to demand characteristics by replicating them almost
      exactly in a between-participants design. In Experiment 3, preference rankings
      revealed a strong relatedness bias together with an inward bias toward the
      spatial envelope of objects to point into the frame. A weak balance effect was
      evident in a multiple regression analysis. Experiment 4 replicated the inward
      bias for the spatial envelope using multiobject groups. Experiment 5 generalized
      the above findings for different objects when observers had to choose between
      image pairs that differed only in interobject distance or degree of balance.
      Strong relatedness effects were again present, but there was no evidence of any
      preference for balance.

PMID- 23145266
TI  - Reading paths, eye drawings, and word islands: Movement in Un coup de des.
AB  - In the framework of an artistic-scientific project on eye-movements during
      reading, my collaborators from the psychology department at the KU Leuven and I
      had a close look at the poem "Un coup de des jamais n'abolira le hasard" ("A
      throw of the dice will never abolish chance") by Stephane Mallarme. The poem is
      an intriguing example of nonlinear writing, of a typographic game with white and
      space, and of an interweaving of different reading lines. These specific features
      evoke multiple reading methods. The animation, Movement in Un coup de des,
      created during the still-ongoing collaboration interweaves a horizontal and a
      vertical reading method, two spontaneous ways of reading that point at the poem's
      intriguing ambiguity. Not only are we interested in different methods of reading;
      the scientific representations of eye movements themselves are a rich source of
      images with much artistic potential. We explore eye movements as "eye drawings"
      in new images characterized both by a scientific and by an artistic perspective.

PMID- 23145268
TI  - Temporal patterns of saccadic eye movements predict individual variation in
      alternation rate during binocular rivalry.
AB  - Interindividual variation has been shown in the rates at which subjects alternate
      in perception during viewing of binocular rivalry and other ambiguous figures. A
      similar pattern of interindividual variation is evident in the rate of eye
      movements. The aim of this study was to determine whether individual differences
      in the rate of binocular rivalry predict individual differences in the rate of
      eye movements. First, participants reported changes in perception during contour
      rivalry. We found that the alternation rate during rivalry varied from 0.15 to
      0.59/s between individuals. Next, participants viewed different visual displays
      while their eye movements were tracked. We found that the rate of saccadic eye
      movements varied by 1.9-4.4/s between individuals. Although the temporal
      characteristics of eye movements and binocular rivalry differed in their absolute
      rate, we found a significant positive correlation between these measures; that
      is, the frequency of saccadic eye movements can predict an individual's rate of
      perceptual alternation during rivalry. These findings suggest a potential link
      between the mechanisms involved in binocular rivalry and those processes involved
      in controlling eye movements.

PMID- 23145267
TI  - Illusory object motion in the centre of a radial pattern: The Pursuit-Pursuing
      illusion.
AB  - A circular object placed in the centre of a radial pattern consisting of thin
      sectors was found to cause a robust motion illusion. During eye-movement pursuit
      of a moving target, the presently described stimulus produced illusory background
      object motion in the same direction as that of the eye movement. In addition, the
      display induced illusory stationary perception of a moving object against the
      whole display motion. In seven experiments, the characteristics of the illusion
      were examined in terms of luminance relationships and figural characteristics of
      the radial pattern. Some potential explanations for these findings are discussed.

PMID- 23145269
TI  - Haptic face aftereffect.
AB  - Face aftereffects (FAEs) are generally thought of as being a visual phenomenon.
      However, recent studies have shown that people can haptically recognize a face.
      Here, I report a haptic, rather than visual, FAE. By using three-dimensional
      facemasks, I found that haptic exploration of the facial expression of the
      facemask causes a subsequently touched neutral facemask to be perceived as having
      the opposite facial expression. The results thus suggest that FAEs can also occur
      in haptic perception of faces.

PMID- 23145270
TI  - Scintillating lustre induced by radial fins.
AB  - Radial lines of Ehrenstein patterns induce illusory scintillating lustre in gray
      disks inserted into the central gaps (scintillating-lustre effect). We report a
      novel variant of this illusion by replacing the radial lines with white and black
      radial fins. Both white and gray disks inserted into the central gaps were
      perceived as scintillating, if the ratio of the black/white fin width were
      balanced (ie, close to 1.0). Thus, the grayness of the central disk is not a
      prerequisite for the scintillation. However, the scintillation was drastically
      reduced when the ratio was imbalanced. Furthermore, the optimal ratio depended on
      the color of the center disks.

PMID- 23145271
TI  - Healthy older observers cannot use biological-motion point-light information
      efficiently within 4 m of themselves.
AB  - Healthy aging is associated with a number of perceptual changes, but measures of
      biological-motion perception have yielded conflicting results. Biological motion
      provides information about a walker, from gender and identity to speed,
      direction, and distance. In our natural environment, as someone approaches us
      (closer distances), the walker spans larger areas of our field of view, the
      extent of which can be underutilized with age. Yet, the effect of age on
      biological-motion perception in such real-world scenarios remains unknown. We
      assessed the effect of age on discriminating walking direction in upright and
      inverted biological-motion patterns, positioned at various distances in virtual
      space. Findings indicate that discrimination is worse at closer distances, an
      effect exacerbated by age. Older adults' performance decreases at distances as
      far away as 4 m, whereas younger adults maintain their performance as close as 1
      m (worse at 0.5 m). This suggests that older observers are limited in their
      capacity to integrate information over larger areas of the visual field and
      supports the notion that age-related effects are more apparent when larger neural
      networks are required to process simultaneous information. This has further
      implications for social contexts where information from biological motion is
      critical.

PMID- 23145273
TI  - Blow-up: a free lunch?
AB  - We consider operations that change the size of images, either shrinks or blow
      ups. Image processing offers numerous possibilities, put at everyone's disposal
      with such computer programs as Adobe Photoshop. We consider a different class of
      operations, aimed at immediate visual awareness, rather than pixel arrays. We
      demonstrate cases of blow-ups that do not sacrifice apparent resolution. This
      apparent information gain is due to "amodal occlusion."

PMID- 23145274
TI  - The emotional effects of violations of causality, or How to make a square
      amusing.
AB  - In Michotte's launching paradigm a square moves up to and makes contact with
      another square, which then moves off more slowly. In the triggering effect, the
      second square moves much faster than the first, eliciting an amusing impression.
      We generated 13 experimental displays in which there was always incongruity
      between cause and effect. We hypothesized that the comic impression would be
      stronger when objects are perceived as living agents and weaker when objects are
      perceived as mechanically non-animated. General findings support our hypothesis.

PMID- 23145272
TI  - Aesthetic valence of visual illusions.
AB  - Visual illusions constitute an interesting perceptual phenomenon, but they also
      have an aesthetic and affective dimension. We hypothesized that the illusive
      nature itself causes the increased aesthetic and affective valence of illusions
      compared with their non-illusory counterparts. We created pairs of stimuli. One
      qualified as a standard visual illusion whereas the other one did not, although
      they were matched in as many perceptual dimensions as possible. The phenomenal
      quality of being an illusion had significant effects on "Aesthetic Experience"
      (fascinating, irresistible, exceptional, etc), "Evaluation" (pleasant, cheerful,
      clear, bright, etc), "Arousal" (interesting, imaginative, complex, diverse, etc),
      and "Regularity" (balanced, coherent, clear, realistic, etc). A subsequent
      multiple regression analysis suggested that Arousal was a better predictor of
      Aesthetic Experience than Evaluation. The findings of this study demonstrate that
      illusion is a phenomenal quality of the percept which has measurable aesthetic
      and affective valence.

PMID- 23145275
TI  - Shadows remain segmented as selectable regions in object-based attention
      paradigms.
AB  - It is unclear how shadows are processed in the visual system. Whilst shadows are
      clearly used as an important cue to localise the objects that cast them, there is
      mixed evidence regarding the extent to which shadows influence the recognition of
      those objects. Furthermore experiments exploring the perception of shadows per se
      have provided evidence that the visual system has less efficient access to the
      detailed form of a region if it is interpreted as a shadow. The current study
      sought to clarify our understanding of the manner in which shadows are
      represented by the visual system by exploring how they influence attention in two
      different object-based attention paradigms. The results provide evidence that
      cues to interpret a region as a shadow do not reduce the extent to which that
      region will result in a within-'object' processing advantage. Thus, whilst there
      is evidence that shadows are processed differently at higher stages of object
      perception, the present result shows that they are still represented as
      distinctly segmented regions as far as the allocation of attention is concerned.
      This result is consistent with the idea that object-based attention phenomena
      result from region-based scene segmentation rather than from the representations
      of objects per se.

PMID- 23145276
TI  - Space-time disarray and visual awareness.
AB  - Local space-time scrambling of optical data leads to violent jerks and
      dislocations. On masking these, visual awareness of the scene becomes cohesive,
      with dislocations discounted as amodally occluding foreground. Such cohesive
      space-time of awareness is technically illusory because ground truth is jumbled
      whereas awareness is coherent. Apparently the visual field is a construction
      rather than a (veridical) perception.

PMID- 23145277
TI  - Aesthetic judgment of triangular shape: compactness and not the golden ratio
      determines perceived attractiveness.
AB  - Many studies over a period of more than a century have investigated the influence
      of the golden ratio on perceived geometric beauty. Surprisingly, very few of
      these studies used triangular shapes. In Experiment 1, we presented right
      triangles that differed in regard to their elongation determined by increasing
      the length of one side relative to another. Attractiveness ratings did not peak
      at the golden ratio, but there was a very strong influence of axis ratio overall.
      Participant ratings were a negative decreasing function of ratio. Triangles that
      pointed upward were judged as significantly more attractive than those that
      pointed down. We interpret these results according to a compactness hypothesis:
      triangles that are more compact are less likely to move or break and are thus
      considered more pleasing. Orientation also affects aesthetics. Upward-pointing
      triangles with a base parallel to the ground, regardless of their compactness,
      are also considered more perceptually stable and attractive. These findings were
      replicated across stimulus type in a second experiment with isosceles triangles
      and across testing procedure in a third experiment using a paired comparison
      technique.

PMID- 23145278
TI  - The same old New Look: Publication bias in a study of wishful seeing.
AB  - A recent study reported evidence of "wishful seeing," where observers reported
      seeing a desired object as being closer than other objects. A statistical
      analysis of the experimental findings reveals evidence of publication bias in the
      study, so the existence of wishful seeing remains unproven.

PMID- 23145279
TI  - The role of head movements and signal spectrum in an auditory front/back
      illusion.
AB  - We used a dynamic auditory spatial illusion to investigate the role of self
      motion and acoustics in shaping our spatial percept of the environment. Using
      motion capture, we smoothly moved a sound source around listeners as a function
      of their own head movements. A lowpass filtered sound behind a listener that
      moved in the direction it would have moved if it had been located in the front
      was perceived as statically located in front. The contrariwise effect occurred if
      the sound was in front but moved as if it were behind. The illusion was strongest
      for sounds lowpass filtered at 500 Hz and weakened as a function of increasing
      lowpass cut-off frequency. The signals with the most high frequency energy were
      often associated with an unstable location percept that flickered from front to
      back as self-motion cues and spectral cues for location came into conflict with
      one another.

PMID- 23145280
TI  - The ingenious Mr Hughes: Combining forced, flat, and reverse perspective all in
      one art piece to pit objects against surfaces.
AB  - The artist Patrick Hughes has ingeniously painted rows of stacked Brillo boxes in
      Forced into Reverse Perspective. The geometry is in reverse perspective,
      predicting only one type of illusory motion for each planar surface for moving
      viewers. He "broke" these surfaces into objects by painting the boxes in three
      types of perspective (planar, forced, and reverse). Our experiments confirmed
      that he succeeded in eliciting different types of illusory motion, including
      "differential motion" between boxes for most viewers. In some sense, this
      illustrates the superiority of secondary (painted) over primary (physical) cues.

PMID- 23145281
TI  - On the matching of seen and felt shape by newly sighted subjects.
AB  - How do we recognize identities between seen shapes and felt ones? Is this due to
      associative learning, or intrinsic connections these sensory modalities? We can
      address this question by testing the capacities of newly sighted subjects to
      match seen and felt shapes, but only if the subjects can see the objects well
      enough to form adequate visual representations of their shapes. In light of this,
      a recent study by R. Held and colleagues fails to demonstrate that their newly
      sighted subjects' inability to match seen and felt shape was due to a lack of
      intermodal connections rather than a purely visual deficit, as the subjects may
      not have been able visually to represent 3D shape in the perspective-invariant
      manner required for intermodal matching. However, the study could be modified in
      any of several ways to help avoid this problem.

PMID- 23145282
TI  - Effects of memory colour on colour constancy for unknown coloured objects.
AB  - The perception of an object's colour remains constant despite large variations in
      the chromaticity of the illumination-colour constancy. Hering suggested that
      memory colours, the typical colours of objects, could help in estimating the
      illuminant's colour and therefore be an important factor in establishing colour
      constancy. Here we test whether the presence of objects with diagnostical colours
      (fruits, vegetables, etc) within a scene influence colour constancy for unknown
      coloured objects in the scene. Subjects matched one of four Munsell papers placed
      in a scene illuminated under either a reddish or a greenish lamp with the Munsell
      book of colour illuminated by a neutral lamp. The Munsell papers were embedded in
      four different scenes-one scene containing diagnostically coloured objects, one
      scene containing incongruent coloured objects, a third scene with geometrical
      objects of the same colour as the diagnostically coloured objects, and one scene
      containing non-diagnostically coloured objects (eg, a yellow coffee mug). All
      objects were placed against a black background. Colour constancy was on average
      significantly higher for the scene containing the diagnostically coloured objects
      compared with the other scenes tested. We conclude that the colours of familiar
      objects help in obtaining colour constancy for unknown objects.

PMID- 23145283
TI  - Perceptual organization of shape, color, shade, and lighting in visual and
      pictorial objects.
AB  - THE MAIN QUESTIONS WE ASKED IN THIS WORK ARE THE FOLLOWING: Where are
      representations of shape, color, depth, and lighting mostly located? Does their
      formation take time to develop? How do they contribute to determining and
      defining a visual object, and how do they differ? How do visual artists use them
      to create objects and scenes? Is the way artists use them related to the way we
      perceive them? To answer these questions, we studied the microgenetic development
      of the object perception and formation. Our hypothesis is that the main object
      properties are extracted in sequential order and in the same order that these
      roles are also used by artists and children of different age to paint objects.
      The results supported the microgenesis of object formation according to the
      following sequence: contours, color, shading, and lighting.

PMID- 23145284
TI  - Looking at Op Art: Gaze stability and motion illusions.
AB  - Various Op artists have used simple geometrical patterns to create the illusion
      of motion in their artwork. One explanation for the observed illusion involves
      retinal shifts caused by small involuntary eye movements that observers make
      while they try to maintain fixation. Earlier studies have suggested a prominent
      role of the most conspicuous of these eye movements, small rapid position shifts
      called microsaccades. Here, we present data that could expand this view with a
      different interpretation. In three experiments, we recorded participants' eye
      movements while they tried to maintain visual fixation when being presented with
      variants of Bridget Riley's Fall, which were manipulated such as to vary the
      strength of induced motion. In the first two experiments, we investigated the
      properties of microsaccades for a set of stimuli with known motion strengths. In
      agreement with earlier observations, microsaccade rates were unaffected by the
      stimulus pattern and, consequently, the strength of induced motion illusion. In
      the third experiment, we varied the stimulus pattern across a larger range of
      parameters and asked participants to rate the perceived motion illusion. The
      results revealed that motion illusions in patterns resembling Riley's Fall are
      perceived even in the absence of microsaccades, and that the reported strength of
      the illusion decreased with the number of microsaccades in the trial. Together,
      the three experiments suggest that other sources of retinal image instability
      than microsaccades, such as slow oculomotor drift, should be considered as
      possible factors contributing to the illusion.

PMID- 23145285
TI  - How simultaneous is the perception of binocular depth and rivalry in plaid
      stimuli?
AB  - Psychophysical experiments have demonstrated that it is possible to perceive both
      binocular depth and rivalry in plaids (Buckthought and Wilson 2007, Vision
      Research47 2543-2556). In a recent study, we investigated the neural substrates
      for depth and rivalry processing with these plaid patterns, when either a depth
      or rivalry task was performed (Buckthought and Mendola 2011, Journal of Vision11
      1-15). However, the extent to which perception of the two stimulus aspects was
      truly simultaneous remained somewhat unclear. In the present study, we introduced
      a new task in which subjects were instructed to perform both depth and rivalry
      tasks concurrently. Subjects were clearly able to perform both tasks at the same
      time, but with a modest, symmetric drop in performance when compared to either
      task carried out alone. Subjects were also able to raise performance levels for
      either task by performing it with a higher priority, with a decline in
      performance for the other task. The symmetric declines in performance are
      consistent with the interpretation that the two tasks are equally demanding of
      attention (Braun and Julesz 1998, Perception & Psychophysics60 1-23). The results
      demonstrate the impressive combination of binocular features that supports
      coincident depth and rivalry in surface perception, within the constraints of
      presumed orientation and spatial frequency channels.

PMID- 23145286
TI  - Crossmodal correspondences: Innate or learned?
AB  - "Are Chimpanzees synaesthetic?" An affirmative answer to this question appeared
      recently in a Nature commentary on a study by Ludwig, Adachi, and Matzuzawa
      (2011) that demonstrated crossmodal correspondences in both chimpanzees and
      humans. Here we question the claim that chimpanzees are synaesthetic. We also
      question the claim that certain crossmodal correspondences are innate. We suggest
      an alternative account for the crossmodal correspondence between auditory pitch
      and visual lightness in terms of the internalization of correlations present in
      the environment. We highlight the limitations of such natural correlation
      approaches to the study of crossmodal correspondences as well as how such claims
      could potentially be tested in future research.

PMID- 23145287
TI  - Artful terms: A study on aesthetic word usage for visual art versus film and
      music.
AB  - Despite the importance of the arts in human life, psychologists still know
      relatively little about what characterises their experience for the recipient.
      The current research approaches this problem by studying people's word usage in
      aesthetics, with a focus on three important art forms: visual art, film, and
      music. The starting point was a list of 77 words known to be useful to describe
      aesthetic impressions of visual art (Augustin et al 2012, Acta Psychologica139
      187-201). Focusing on ratings of likelihood of use, we examined to what extent
      word usage in aesthetic descriptions of visual art can be generalised to film and
      music. The results support the claim of an interplay of generality and
      specificity in aesthetic word usage. Terms with equal likelihood of use for all
      art forms included beautiful, wonderful, and terms denoting originality.
      Importantly, emotion-related words received higher ratings for film and music
      than for visual art. To our knowledge this is direct evidence that aesthetic
      experiences of visual art may be less affectively loaded than, for example,
      experiences of music. The results render important information about aesthetic
      word usage in the realm of the arts and may serve as a starting point to develop
      tailored measurement instruments for different art forms.

PMID- 23145289
TI  - Faces of neuroscience.

PMID- 23145288
TI  - Luminance distribution modifies the perceived freshness of strawberries.
AB  - Material perception studies focus on the analysis of visual cues that may
      underlie the ability to distinguish between the different properties of an
      object. Herein, we investigated the effects of luminance distribution on the
      perceived freshness of a strawberry independent from its colour information. We
      took photographs of the degradation of a strawberry over 169 hours in a
      controlled environment, then presented cropped square patches of the original
      images to subjects who then rated the perceived freshness using a visual analogue
      scale. Freshness ratings were significantly highly correlated with statistical
      measures of the luminance and colour channels. To clarify which of these visual
      cues affects freshness perception, we created artificial images by modifying only
      the luminance distribution and keeping the colour information unchanged. The
      modification of luminance resulted in a highly correlated change in freshness
      perception, suggesting that luminance visual cues are essential to the freshness
      perception of strawberries. Finally, by eliminating the colour information from
      the images, we examined the contribution of luminance distribution independent of
      colour information and found that luminance information suffices for accurate
      estimation of strawberry freshness.

PMID- 23145290
TI  - Eye of the beholder: Symmetry perception in social judgments based on whole body
      displays.
AB  - External bilateral symmetry is a biological marker of normal development and is
      considered a signal of health and attractiveness across species. Because most
      human interactions are dynamic, it was hypothesized that observers would be able
      to perceive spatiotemporal symmetry-symmetry in motion-in human point-light
      walkers. It was also hypothesized that observers would rate symmetrical walkers
      as healthy and attractive. Symmetrical and asymmetrical figures were presented to
      adult participants (n = 22) in motion and as static images with motion implied.
      Static symmetry was readily perceived, and symmetrical figures were judged
      significantly healthier and more attractive than asymmetrical figures. However,
      observers were unable to discriminate symmetry in dynamic presentations. These
      data provide preliminary evidence of a temporal summation window for a dynamic
      symmetry perception.

PMID- 23145292
TI  - Navigating the vision science Internet.

PMID- 23145291
TI  - The cognitive neuroscience of crossmodal correspondences.
AB  - In a recent article, N. Bien, S. ten Oever, R. Goebel, and A. T. Sack (2012) used
      event-related potentials to investigate the consequences of crossmodal
      correspondences (the "natural" mapping of features, or dimensions, of experience
      across sensory modalities) on the time course of neural information processing.
      Then, by selectively lesioning the right intraparietal cortex using transcranial
      magnetic stimulation, these researchers went on to demonstrate (for the first
      time) that it is possible to temporarily eliminate the effect of crossmodal
      congruency on multisensory integration (specifically on the spatial ventriloquism
      effect). These results are especially exciting given the possibility that the
      cognitive neuroscience methodology utilized by Bien et al. (2012) holds for
      dissociating between putatively different kinds of crossmodal correspondence in
      future research.

PMID- 23145293
TI  - Perception while watching movies: Effects of physical screen size and scene type.
AB  - Over the last decade, television screens and display monitors have increased in
      size considerably, but has this improved our televisual experience? Our working
      hypothesis was that the audiences adopt a general strategy that "bigger is
      better." However, as our visual perceptions do not tap directly into basic
      retinal image properties such as retinal image size (C. A. Burbeck, 1987), we
      wondered whether object size itself might be an important factor. To test this,
      we needed a task that would tap into the subjective experiences of participants
      watching a movie on different-sized displays with the same retinal subtense. Our
      participants used a line bisection task to self-report their level of "presence"
      (i.e., their involvement with the movie) at several target locations that were
      probed in a 45-min section of the movie "The Good, The Bad, and The Ugly."
      Measures of pupil dilation and reaction time to the probes were also obtained. In
      Experiment 1, we found that subjective ratings of presence increased with
      physical screen size, supporting our hypothesis. Face scenes also produced higher
      presence scores than landscape scenes for both screen sizes. In Experiment 2,
      reaction time and pupil dilation results showed the same trends as the presence
      ratings and pupil dilation correlated with presence ratings, providing some
      validation of the method. Overall, the results suggest that real-time measures of
      subjective presence might be a valuable tool for measuring audience experience
      for different types of (i) display and (ii) audiovisual material.

PMID- 23145294
TI  - Using an oculomotor signature as an indicator of aesthetic preference.
AB  - Eye movements are strongly influenced by the task given to an observer. The
      immediacy of such eye movements, which are difficult to control consciously,
      offers the potential to explore highly variable subjective evaluations, such as
      aesthetic preference, with reliable objective measures. We presented a variety of
      images in sets of 2, 4, or 8 items for different durations and analyzed
      oculomotor statistics such as cumulative fixation duration, refixations, and the
      sequence of fixations while participants searched for their preferred image,
      after which participants indicated their preference using a button press. The
      total amount of time spent looking at any image correlates with selection
      preference and does so increasingly well with longer presentation duration. For
      short presentations, the first and last fixations correlate better with image
      preference. All response measures become increasingly variable as the number and
      complexity of presented images are increased. A weighted combination of these
      measures can significantly improve the correlation with preference, suggesting a
      "signature" which could be used as a reliable indicator for task-free subjective
      evaluation of stimuli in visual psychophysics. Its role as an improved fitness
      function in visually driven evolutionary algorithms is discussed.

PMID- 23145295
TI  - On the rules of integration of crowded orientation signals.
AB  - Crowding is related to an integration of feature signals over an inappropriately
      large area in the visual periphery. The rules of this integration are still not
      well understood. This study attempts to understand how the orientation signals
      from the target and flankers are combined. A target Gabor, together with 2, 4, or
      6 flanking Gabors, was briefly presented in a peripheral location (4 degrees 
      eccentricity). The observer's task was to identify the orientation of the target
      (eight-alternative forced-choice). Performance was found to be nonmonotonically
      dependent on the target-flanker orientation difference (a drop at intermediate
      differences). For small target-flanker differences, a strong assimilation bias
      was observed. An effect of the number of flankers was found for heterogeneous
      flankers only. It appears that different rules of integration are used, dependent
      on some salient aspects (target pop-out, homogeneity-heterogeneity) of the
      stimulus pattern. The strategy of combining simple rules may be explained by the
      goal of the visual system to encode potentially important aspects of a stimulus
      with limited processing resources and using statistical regularities of the
      natural visual environment.

PMID- 23145296
TI  - Empirical aesthetics, the beautiful challenge: An introduction to the special
      issue on Art & Perception.
AB  - The i-Perception special issue Art & Perception is based on the Art & Perception
      Conference 2010 in Brussels. Our vision with this conference was to bring
      together artists and vision scientists from different backgrounds to exchange
      views and state-of-the-art knowledge on art perception and aesthetics. The
      complexity of the experience of art and of aesthetic phenomena, in general, calls
      for specific research approaches, for which interdisciplinarity seems to be key.
      Following this logic, the special issue Art & Perception contains contributions
      by artists and vision scientists with different methodological approaches. The
      contributions span a wide range of topics, but are all centred around two
      questions: How can one understand art perception and aesthetics from a
      psychological point of view, and how is this reflected in art itself?

PMID- 23145297
TI  - Children's and adults' size estimates at near and far distances: A test of the
      perceptual learning theory of size constancy development.
AB  - This study tested the perceptual learning theory of size constancy development,
      which proposes that children younger than 9 years are relatively insensitive to
      monocular cues for distance and size, and that developmental changes in far
      distance size estimation result from increasing sensitivity to these cues. This
      theory predicts that before 10 years, children will make less accurate size
      judgments at far distances under monocular than under binocular viewing
      conditions. Five age groups were tested: 5-6, 7-8, 9-10, 19-28, and 50+ years.
      Participants judged the size of a standard disc, from viewing distances of 6.1
      and 61 m, by pointing at 1 of 9 nearby comparison discs. Testing was conducted
      under both monocular and binocular viewing conditions. Five- to 6-year-olds
      underestimated object size at the far distance, 7- to 8-, 9- to 10-year-olds, and
      older adults made size estimates that were close to accurate, and the young
      adults significantly overestimated size. At the near distance, all age groups
      underestimated size and no age differences were found. Contrary to predictions
      from the perceptual learning theory, viewing condition had no significant effect
      on size estimates.

PMID- 23145298
TI  - Awareness of the light field: the case of deformation.
AB  - Human observers group local shading patterns into global super-patterns that
      appear to be illuminated in some unitary fashion. Many years ago, this was
      noticed for the case of uniform, unidirectional illumination. Recently, we found
      that it also applies to convergent and divergent illumination flows, but that
      human observers are blind to rotational light flow patterns (in the sense of
      being unable to group the local shading patterns). We now report that human
      observers are also blind to deformation patterns. This is perhaps interesting
      because convergent, divergent, rotational, and deformation patterns all occur in
      natural light fields. This is an idiosyncrasy of the human visual system, on par
      with the fact that visual awareness fails to present the observer with saddle
      shapes.

PMID- 23145299
TI  - A developmental difference in shape processing and word-shape associations
      between 4 and 6.5 year olds.
AB  - In distinguishing individual shapes (defined by their contours), older children
      (6.5 years of age on average) performed better than younger children (4 years of
      age on average), and, although the task did not involve any categorization or
      generalization, the error pattern was qualitatively affected by shape differences
      that are generally common distinctions between objects belonging to different
      categories. The influence of these shape differences was also observed for
      unfamiliar shapes, demonstrating that the influence of categorization experience
      was not modulated by the retrieval of shape features from known categories but
      rather related to a different perception of shape by age. The results suggest a
      direct influence of categorization experience on more abstract shape processing.
      When children were distinguishing shapes, new words were paired with the target
      shapes, and in 2 additional tasks, the acquired name-shape associations were
      tested. The younger age group was able to remember more words correctly.

PMID- 23145300
TI  - Prevalence effect in haptic search.
AB  - In visual search tasks, the ratio of target-present to target-absent trials has
      important effects on miss rates. In this study, we examined whether the target
      prevalence effect occurs in a haptic search task by using artificial tactile
      maps. The results indicated that target prevalence has effects on miss rates,
      sensitivity, and criterion. Moreover, an increase in miss rates in the low
      prevalence condition (10%) was strongly correlated with a decrease in search
      termination times (target-absent reaction times). These results suggest that the
      prevalence effect on haptic search is caused by a decrease in the search
      termination time and a shift in decision criterion and a decrease in sensitivity.

PMID- 23145301
TI  - Afterimages from unseen stimuli.
AB  - Observers adapted to a field of randomly coloured twinkling tiles, in which was
      embedded a faint, subthreshold green letter. Observers failed to discern this
      letter, but they readily reported its pink afterimage afterwards. This
      demonstrates a storage of changing colours over time; adaptation occurs for the
      average of each retinal point.

PMID- 23145302
TI  - Binocular rivalry for beginners.

PMID- 23145303
TI  - Local computation of lightness on articulated surrounds.
AB  - Lightness of a grey target on a uniform light (or dark) surround changes by
      articulating the surround (articulation effect). To elucidate the processing of
      lightness underlying the articulation effect, the present study introduced
      transparency over a dark surround and investigated its effects on lightness of
      the target. The transparency was produced by adding a contiguous external field
      to the dark surround while keeping local stimulus configuration constant. Results
      showed that the target lightness did not change on the articulated surround when
      a dark transparent filter was perceived over the target, although it did on the
      uniform surround. These results suggest that image decomposition into a
      transparent filter and an underlying surface does not necessarily change
      lightness of the surface if the surface is articulated. Moreover, the present
      study revealed that articulating the surround does not always enhance lightness
      contrast; it can reduce the contrast effect when the target luminance is not the
      highest within the surround. These findings are consistent with the theoretical
      view that lightness perception on articulated surfaces is determined locally
      within a spatially limited region, and they also place a constraint on how the
      luminance distribution within the limited region is scaled.

PMID- 23145304
TI  - Looking at two paintings at once: Luminance edges can gate colors.
AB  - Two paintings, O1 and O2, were split into their luminance (grayscale) components
      L1, L2 and their color components C1, C2. The two color components, C1, C2, were
      transparently superimposed. Adding the grayscale of the first painting (= C1 + C2
      + L1) looked like the original O1, while adding the grayscale of the second
      painting (= C1 + C2 + L2) looked like the original O2. CONCLUSION: the luminance
      contours selected or gated the congruent color contours and ignored non-congruent
      colors from the other painting.

PMID- 23145305
TI  - Grouping by closure influences subjective regularity and implicit preference.
AB  - A reflection between a pair of contours is more rapidly detected than a
      translation, but this effect is stronger when the contours are closed to form a
      single object compared to when they are closed to form 2 objects with a gap
      between them. That is, grouping changes the relative salience of different
      regularities. We tested whether this manipulation would also change preference
      for reflection or translation. We measured preference for these patterns using
      the Implicit Association Test (IAT). On some trials, participants saw words that
      were either positive or negative and had to classify them as quickly as possible.
      On interleaved trials, they saw reflection or translation patterns and again had
      to classify them. Participants were faster when 1 button was used for reflection
      and positive words and another button was used for translation and negative
      words, compared to when the reverse response mapping was used (translation and
      positive vs. reflection and negative). This reaction time difference indicates an
      implicit preference for reflection over translation. However, the size of the
      implicit preference was significantly reduced in the Two-objects condition. We
      concluded that factors that affect perceptual sensitivity also systematically
      affect implicit preference formation.

PMID- 23145306
TI  - Interaction of depth probes and style of depiction.
AB  - We study the effect of stylistic differences on the nature of pictorial spaces as
      they appear to an observer when looking into a picture. Four pictures chosen from
      diverse styles of depiction were studied by 2 different methods. Each method
      addresses pictorial depth but draws on a different bouquet of depth cues. We find
      that the depth structures are very similar for 8 observers, apart from an
      idiosyncratic depth scaling (up to a factor of 3). The differences between
      observers generalize over (very different) pictures and (very different) methods.
      They are apparently characteristic of the person. The differences between depths
      as sampled by the 2 methods depend upon the style of the picture. This is the
      case for all observers except one.

PMID- 23145307
TI  - The utility of defocus blur in binocular depth perception.
AB  - The question of whether defocus blur is a quantitative cue for depth perception
      is a topic of renewed interest. A recent study suggests that relative defocus
      blur can be used in computing depth throughout the visual field, particularly in
      regions where disparity loses precision. However, elements of the study's
      experimental design and theoretical analysis appear to undermine this claim.
      First, the study did not provide evidence that blur can be used as a quantitative
      depth cue. It only measured blur discrimination thresholds, not perceived depth
      from for blur. Second, the study's conceptualization of the complementary use of
      blur and disparity, and related conjectures, are based on the specific viewing
      geometry and fixation distance tested. They do not appear to generalize to
      natural viewing situations and tasks. I suggest a different way in which defocus
      blur might affect depth perception. Because depth-of-focus blur is a cue to
      egocentric distance, it could contribute to quantitative depth perception by
      scaling depth relations specified by other relative depth cues.

PMID- 23145308
TI  - View-based matching can be more than image matching: The importance of
      considering an animal's perspective.
AB  - Using vision for navigation is important for many animals and a common debate is
      the extent to which spatial performance can be explained by "simple" view-based
      matching strategies. We discuss, in the context of recent work, how confusion
      between image-matching algorithms and the broader class of view-based navigation
      strategies, is hindering the debate around the use of vision in spatial
      cognition. A proper consideration of view-based matching strategies requires an
      understanding of the visual information available to a given animal within a
      particular experiment.

PMID- 23145309
TI  - Hearing mouth shapes: Sound symbolism and the reverse McGurk effect.
AB  - In their recent article, Sweeny, Guzman-Martinez, Ortega, Grabowecky, and Suzuki
      (2012) demonstrate that heard speech sounds modulate the perceived shape of
      briefly presented visual stimuli. Ovals, whose aspect ratio (relating width to
      height) varied on a trial-by-trial basis, were rated as looking wider when a
      /woo/ sound was presented, and as taller when a /wee/ sound was presented
      instead. On the one hand, these findings add to a growing body of evidence
      demonstrating that audiovisual correspondences can have perceptual (as well as
      decisional) effects. On the other hand, they prompt a question concerning their
      origin. Although the currently popular view is that crossmodal correspondences
      are based on the internalization of the natural multisensory statistics of the
      environment (see Spence, 2011), these new results suggest instead that certain
      correspondences may actually be based on the sensorimotor responses associated
      with human vocalizations. As such, the findings of Sweeny et al. help to breathe
      new life into Sapir's (1929) once-popular "embodied" explanation of sound
      symbolism. Furthermore, they pose a challenge for those psychologists wanting to
      determine which among a number of plausible accounts best explains the available
      data on crossmodal correspondences.

PMID- 23145310
TI  - The power of liking: Highly sensitive aesthetic processing for guiding us through
      the world.
AB  - Assessing liking is one of the most intriguing and influencing types of
      processing we experience day by day. We can decide almost instantaneously what we
      like and are highly consistent in our assessments, even across cultures. Still,
      the underlying mechanism is not well understood and often neglected by vision
      scientists. Several potential predictors for liking are discussed in the
      literature, among them very prominently typicality. Here, we analysed the impact
      of subtle changes of two perceptual dimensions (shape and colour saturation) of
      three-dimensional models of chairs on typicality and liking. To increase the
      validity of testing, we utilized a test-adaptation-retest design for extracting
      sensitivity data of both variables from a static (test only) as well as from a
      dynamic perspective (test-retest). We showed that typicality was only influenced
      by shape properties, whereas liking combined processing of shape plus saturation
      properties, indicating more complex and integrative processing. Processing the
      aesthetic value of objects, persons, or scenes is an essential and sophisticated
      mechanism, which seems to be highly sensitive to the slightest variations of
      perceptual input.

PMID- 23145311
TI  - Characterization of coagulation factor synthesis in nine human primary cell
      types.
AB  - The coagulation/fibrinolysis system is essential for wound healing after vascular
      injury. According to the standard paradigm, the synthesis of most coagulation
      factors is restricted to liver, platelets and endothelium. We challenged this
      interpretation by measuring coagulation factors in nine human primary cell types.
      FX mRNA was expressed by fibroblasts, visceral preadipocytes/adipocytes and
      hepatocytes, but not in macrophages or other cells. All cells expressed FVIII
      except endothelial cells. Fibroblasts, endothelial cells and macrophages produced
      thrombomodulin but not FV. Interestingly, vascular-related cells
      (platelets/monocytes) that expressed FV did not express FX and vice versa.
      Monocytes expressed FV, FVIII and FXIIIA, which are positive regulators of clot
      formation, but these cells also contained thrombomodulin, a negative regulator of
      coagulation. Our data show that the expression of coagulation factors is much
      more complex than previously thought, and we speculate that this intricate
      regulation of coagulation factor expression is necessary for correct fine-tuning
      of fibrinogenesis versus fibrinolysis.

PMID- 23145313
TI  - Floating nematic phase in colloidal platelet-sphere mixtures.
AB  - The phase behaviour of colloidal dispersions is interesting for fundamental
      reasons and for technological applications such as photonic crystals and
      electronic paper. Sedimentation, which in everyday life is relevant from blood
      analysis to the shelf life of paint, is a means to determine phase boundaries by
      observing distinct layers in samples that are in sedimentation-diffusion
      equilibrium. However, disentangling the effects due to interparticle
      interactions, which generate the bulk phase diagram, from those due to gravity is
      a complex task. Here we show that a line in the space of chemical potentials
      u(i), where i labels the species, represents a sedimented sample and that each
      crossing of this sedimentation path with a binodal generates an interface under
      gravity. Complex phase stacks can result, such as the sandwich of a floating
      nematic layer between top and bottom isotropic phases that we observed in a
      mixture of silica spheres and gibbsite platelets.

PMID- 23145312
TI  - Autocrine stimulation of clear-cell renal carcinoma cell migration in hypoxia via
      HIF-independent suppression of thrombospondin-1.
AB  - Thrombospondin-1 is a matricellular protein with potent antitumour activities,
      the levels of which determine the fate of many different tumours, including renal
      carcinomas. However, the factors that regulate this protein remain unclear. In
      renal carcinomas, hypoxic conditions enhance the expression of angiogenic factors
      that help adapt tumour cells to their hostile environment. Therefore, we
      hypothesized that anti-angiogenic factors should correspondingly be dampened.
      Indeed, we found that hypoxia decreased the thrombospondin-1 protein in several
      clear cell renal carcinoma cell lines (ccRCC), although no transcriptional
      regulation was observed. Furthermore, we proved that hypoxia stimulates multiple
      signals that independently contribute to diminish thrombospondin-1 in ccRCC,
      which include a decrease in the activity of oxygen-dependent prolylhydroxylases
      (PHDs) and activation of the PI3K/Akt signalling pathway. In addition,
      thrombospondin-1 regulation in hypoxia proved to be important for ccRCC cell
      migration and invasion.

PMID- 23145314
TI  - Nano-visualization of oriented-immobilized IgGs on immunosensors by high-speed
      atomic force microscopy.
AB  - Oriented immobilization of sensing molecules on solid phases is an important
      issue in biosensing. In case of immunosensors, it is essential to scrutinize not
      only the direction and shape of immunoglobulin G (IgG) in solution but also the
      real-time movement of IgGs, which cannot be achieved by conventional techniques.
      Recently, we developed bio-nanocapsules (BNCs) displaying a tandem form of the
      IgG Fc-binding Z domain derived from Staphylococcus aureus protein A (ZZ-BNC) to
      enhance the sensitivity and antigen-binding capacity of IgG via oriented
      immobilization. Here, we used high-speed atomic force microscopy (HS-AFM) to
      reveal the fine surface structure of ZZ-BNC and observe the movement of mouse
      IgG3 molecules tethered onto ZZ-BNC in solution. ZZ-BNC was shown to act as a
      scaffold for oriented immobilization of IgG, enabling its Fv regions to undergo
      rotational Brownian motion. Thus, HS-AFM could decipher real-time movement of
      sensing molecules on biosensors at the single molecule level.

PMID- 23145315
TI  - Modulating DNA translocation by a controlled deformation of a PDMS nanochannel
      device.
AB  - Several strategies have been developed for the control of DNA translocation in
      nanopores and nanochannels. However, the possibility to reduce the molecule speed
      is still challenging for applications in the field of single molecule analysis,
      such as ultra-rapid sequencing. This paper demonstrates the possibility to alter
      the DNA translocation process through an elastomeric nanochannel device by
      dynamically changing its cross section. More in detail, nanochannel deformation
      is induced by a macroscopic mechanical compression of the polymeric device. This
      nanochannel squeezing allows slowing down the DNA molecule passage inside it.
      This simple and low cost method is based on the exploitation of the elastomeric
      nature of the device, can be coupled with different sensing techniques, is
      applicable in many research fields, such as DNA detection and manipulation, and
      is promising for further development in sequencing technology.

PMID- 23145316
TI  - The origin of fluorescence from graphene oxide.
AB  - Time-resolved fluorescence measurements of graphene oxide in water show
      multiexponential decay kinetics ranging from 1 ps to 2 ns. Electron-hole
      recombination from the bottom of the conduction band and nearby localized states
      to wide-range valance band is suggested as origin of the fluorescence. Excitation
      wavelength dependence of the fluorescence was caused by relative intensity
      changes of few emission species. By introducing the molecular orbital concept,
      the dominant fluorescence was found to originate from the electronic transitions
      among/between the non-oxidized carbon regions and the boundary of oxidized carbon
      atom regions, where all three kinds of functionalized groups C-O, C = O and O = C
      OH were participating. In the visible spectral range, the ultrafast fluorescence
      of graphene oxide was observed for the first time.

PMID- 23145317
TI  - Sequential detection of temporal communities by estrangement confinement.
AB  - Temporal communities are the result of a consistent partitioning of nodes across
      multiple snapshots of an evolving network, and they provide insights into how
      dense clusters in a network emerge, combine, split and decay over time. To
      reliably detect temporal communities we need to not only find a good community
      partition in a given snapshot but also ensure that it bears some similarity to
      the partition(s) found in the previous snapshot(s), a particularly difficult task
      given the extreme sensitivity of community structure yielded by current methods
      to changes in the network structure. Here, motivated by the inertia of inter-node
      relationships, we present a new measure of partition distance called
      estrangement, and show that constraining estrangement enables one to find
      meaningful temporal communities at various degrees of temporal smoothness in
      diverse real-world datasets. Estrangement confinement thus provides a principled
      approach to uncovering temporal communities in evolving networks.

PMID- 23145318
TI  - Size effects in atomic-level epitaxial redistribution process of RuO2 over TiO2.
AB  - Controls over the atomic dispersity and particle shape of noble metal catalysts
      are the major qualities determining their usability in industrial runs, but they
      are usually difficult to be simultaneously realized. Inspired from the Deacon
      catalyst in which RuO(2) can form epitaxial layers on the surfaces of Rutile
      TiO(2), here we have investigated the shape evolution process of RuO(2)
      nanoparticles on the surface of P25 TiO(2). It is found that size effects exist
      in this process and RuO(2) nanoparticles with sizes ~sub-2 nm can be transformed
      into epitaxial layers while nanoparticles with bigger sizes are not apt to change
      their shapes. Based on a thermodynamic model, we infer such transformation
      process is jointly driven by the surface tension and interfacial lattice match
      between the nanoparticles and substrates, which may be suggestive for the design
      of noble metal catalysts integrating both active crystal planes and high atomic
      exposure ratios.

PMID- 23145319
TI  - Multimodal imaging of human cerebellum - merging X-ray phase microtomography,
      magnetic resonance microscopy and histology.
AB  - Imaging modalities including magnetic resonance imaging and X-ray computed
      tomography are established methods in daily clinical diagnosis of human brain.
      Clinical equipment does not provide sufficient spatial resolution to obtain
      morphological information on the cellular level, essential for applying minimally
      or non-invasive surgical interventions. Therefore, generic data with lateral sub
      micrometer resolution have been generated from histological slices post mortem.
      Sub-cellular spatial resolution, lost in the third dimension as a result of
      sectioning, is obtained using magnetic resonance microscopy and micro computed
      tomography. We demonstrate that for human cerebellum grating-based X-ray phase
      tomography shows complementary contrast to magnetic resonance microscopy and
      histology. In this study, the contrast-to-noise values of magnetic resonance
      microscopy and phase tomography were comparable whereas the spatial resolution in
      phase tomography is an order of magnitude better. The registered data with their
      complementary information permit the distinct segmentation of tissues within the
      human cerebellum.

PMID- 23145320
TI  - Loss of maternal annexin A5 increases the likelihood of placental platelet
      thrombosis and foetal loss.
AB  - Antiphospholipid syndrome is associated with an increased risk of thrombosis and
      pregnancy loss. Annexin A5 (Anxa5) is a candidate autoantigen. It is not known,
      however, whether endogenous Anxa5 prevents foetal loss during normal pregnancy.
      We found significant reductions in litter size and foetal weight in Anxa5-null
      mice (Anxa5-KO). These changes occurred even when only the mother was Anxa5-KO. A
      small amount of placental fibrin deposition was observed in the decidual tissues,
      but did not noticeably differ between wild-type and Anxa5-KO mice. However,
      immunoreactivity for integrin beta 3/CD61, a platelet marker, was demonstrated
      within thrombi in the arterial canals only in Anxa5-KO mothers. Subcutaneous
      administration of the anticoagulant heparin to pregnant Anxa5-KO mice
      significantly reduced pregnancy loss, suggesting that maternal Anxa5 is crucial
      for maintaining intact placental circulation. Hence, the presence of maternal
      Anxa5 minimises the risk of thrombosis in the placental circulation and reduces
      the risk of foetal loss.

PMID- 23145322
TI  - High temperatures-related elderly mortality varied greatly from year to year:
      important information for heat-warning systems.
AB  - We examined the variation in association between high temperatures and elderly
      mortality (age >= 75 years) from year to year in 83 US cities between 1987 and
      2000. We used a Poisson regression model and decomposed the mortality risk for
      high temperatures into: a "main effect" due to high temperatures using lagged non
      linear function, and an "added effect" due to consecutive high temperature days.
      We pooled yearly effects across both regional and national levels. The high
      temperature effects (both main and added effects) on elderly mortality varied
      greatly from year to year. In every city there was at least one year where higher
      temperatures were associated with lower mortality. Years with relatively high
      heat-related mortality were often followed by years with relatively low
      mortality. These year to year changes have important consequences for heat
      warning systems and for predictions of heat-related mortality due to climate
      change.

PMID- 23145323
TI  - Exchange coupling driven omnidirectional rotatable anisotropy in ferrite doped
      CoFe thin film.
AB  - Isotropic magnetic materials with high resonant frequencies are useful for
      applications in microwave devices. Undoped CoFe thin films, as common soft
      magnetic materials with high saturation magnetization, show isotropic
      characteristics but no high frequency response. Here, we use ferrite doped CoFe
      thin film to realize a resonant frequency higher than 4.5 GHz at all
      orientations. The exchange coupling between ferrimagnet and ferromagnet is
      assumed to play a key role on the omnidirectional rotatable anisotropy.

PMID- 23145321
TI  - A novel tumor suppressor network in squamous malignancies.
AB  - The specific ablation of Rb1 gene in stratified epithelia (Rb(F/F);K14cre)
      promotes proliferation and altered differentiation but is insufficient to produce
      spontaneous tumors. The pRb relative, p107, compensates some of the functions of
      pRb in these tissues; however, Rb(F/F);K14cre;p107(-/-) mice die postnatally.
      Here we show, using an inducible mouse model (Rb(F/F);K14creER(TM)), that p107
      exerts specific tumor suppressor functions in the absence of pRb in stratified
      epithelia. The simultaneous absence of pRb and p107 produces impaired p53
      transcriptional functions and reduction of Pten expression, allowing spontaneous
      squamous carcinoma development. These tumors display significant overlap with
      human squamous carcinomas, supporting that Rb(F/F);K14creER(TM);p107(-/-) mice
      might constitute a new model for these malignancies. Remarkably tumor development
      in vivo is partially alleviated by mTOR inhibition. These data demonstrate the
      existence of a previously unreported functional connection between pRb, Pten and
      p53 tumor suppressors, through p107, of a particular relevance in squamous tumor
      development.

PMID- 23145324
TI  - Phylogenetics links monster larva to deep-sea shrimp.
AB  - Mid-water plankton collections commonly include bizarre and mysterious
      developmental stages that differ conspicuously from their adult counterparts in
      morphology and habitat. Unaware of the existence of planktonic larval stages,
      early zoologists often misidentified these unique morphologies as independent
      adult lineages. Many such mistakes have since been corrected by collecting
      larvae, raising them in the lab, and identifying the adult forms. However,
      challenges arise when the larva is remarkably rare in nature and relatively
      inaccessible due to its changing habitats over the course of ontogeny. The mid
      water marine species Cerataspis monstrosa (Gray 1828) is an armored crustacean
      larva whose adult identity has remained a mystery for over 180 years. Our
      phylogenetic analyses, based in part on recent collections from the Gulf of
      Mexico, provide definitive evidence that the rare, yet broadly distributed larva,
      C. monstrosa, is an early developmental stage of the globally distributed
      deepwater aristeid shrimp, Plesiopenaeus armatus. Divergence estimates and
      phylogenetic relationships across five genes confirm the larva and adult are the
      same species. Our work demonstrates the diagnostic power of molecular systematics
      in instances where larval rearing seldom succeeds and morphology and habitat are
      not indicative of identity. Larval-adult linkages not only aid in our
      understanding of biodiversity, they provide insights into the life history,
      distribution, and ecology of an organism.

PMID- 23145325
TI  - Interannual variations of soil organic carbon fractions in unmanaged volcanic
      soils (Canary Islands, Spain).
AB  - The stability over time of the organic C stocked in soils under undisturbed
      ecosystems is poorly studied, despite being suitable for detecting changes
      related to climate fluctuations and global warming. Volcanic soils often show
      high organic C contents due to the stabilization of organic matter by short-range
      ordered minerals or Al-humus complexes. We investigated the dynamics of different
      organic C fractions in volcanic soils of protected natural ecosystems of the
      Canary Islands (Spain) to evaluate the stability of their C pools. The study was
      carried out in 10 plots, including both undisturbed and formerly disturbed
      ecosystems, over two annual periods. C inputs to (litterfall) and outputs from
      (respiration) the soil, root C stocks (0-30 cm), soil organic C (SOC) fractions
      belonging to C pools with different degrees of biogeochemical stability -total
      oxidisable C (TOC), microbial biomass C (MBC), water soluble C (WSC), hot-water
      extractable C (HWC), humic C (HSC), - and total soil N (TN) (at 0-15 and 15-30
      cm) were measured seasonally.A statistically significant interannual increase in
      CO(2) emissions and a decrease in the SOC, mainly at the expense of the most
      labile organic forms, were observed, while the root C stocks and litterfall
      inputs remained relatively constant over the study period. The observed changes
      may reflect an initial increase in SOC resulting from low soil respiration rates
      due to drought during the first year of study. The soils of nearly mature
      ecosystems were more apparently affected by C losses, while those undergoing the
      process of active natural regeneration exhibited disguised C loss because of the
      C sequestration trend that is characteristic of progressive ecological
      succession.

PMID- 23145326
TI  - Detecting immigrants in a highly genetically homogeneous spiny lobster population
      (Palinurus elephas) in the northwest Mediterranean Sea.
AB  - We investigated the genetic structure of early benthic juveniles of the spiny
      lobster Palinurus elephas in the northwest Mediterranean Sea by means of ten
      polymorphic microsatellite markers. Non-metric Multidimensional Scaling coupled
      with assignment tests were used as a new approach to further delimit a reference
      population inside a genetically homogeneous pool of individuals and test for the
      presence of long distance immigrants. From this approach, we found that most
      early benthic juveniles collected while settling in the northwest Mediterranean
      Sea originated from a common larval pool. However, 4.2% of the individuals were
      classified as immigrants from other genetically differentiated populations, with
      more immigrants in the south than in the north of the sampled basin. Given
      currents in the northwest Mediterranean Sea and the long pelagic larval phase of
      P. elephas that lasts several months, this result suggest a restricted
      homogenized zone in the studied basin with some individuals probably coming from
      more differentiated populations through the Almeria-Oran Front or the Strait of
      Sicily.

PMID- 23145327
TI  - Rainfall can explain adaptive phenotypic variation with high gene flow in the New
      Holland Honeyeater (Phylidonyris novaehollandiae).
AB  - Identifying environmentally driven changes in traits that serve an ecological
      function is essential for predicting evolutionary outcomes of climate change. We
      examined population genetic structure, sex-specific dispersal patterns, and
      morphology in relation to rainfall patterns across an island and three peninsulas
      in South Australia. The study system was the New Holland Honeyeater (Phylidonyris
      novaehollandiae), a nectarivorous passerine that is a key pollinator species. We
      predicted that rainfall-related mechanisms would be driving local adaptation of
      morphological traits, such that in areas of lower rainfall, where nectar is less
      available, more insectivorous traits - shorter, deeper bills, longer tarsi, and
      longer wings - would be favored. The study populations differed in phenotype
      across the Eyre, Yorke, and Fleurieu Peninsulas and Kangaroo Island despite high
      gene flow (single continuous population) and sex-biased dispersal (males were
      philopatric and females dispersed). We tested the role of rainfall in shaping the
      observed phenotypic differences, and found strong support for our predicted
      relationships: birds in areas of higher rainfall had higher condition indices, as
      well as longer bill-head length, deeper bills, and shorter tarsi. Bill depth in
      males in high-rainfall sites showed signals of stabilizing selection, suggesting
      local adaptation. In addition to these local indications of selection, a global
      pattern of directional selection toward larger size for bill-head length, bill
      nostril length, and wing length was also observed. We suggest this pattern may
      reflect an adaptive response to the relatively dry conditions that South
      Australia has experienced over the last decade. We conclude that rainfall has
      shaped aspects of phenology in P. novaehollandiae, both locally, with different
      patterns of stabilizing and directional selection, and globally, with evidence of
      adaptive divergence at a landscape scale.

PMID- 23145328
TI  - Extensive introgressive hybridization within the northern oriole group (Genus
      Icterus) revealed by three-species isolation with migration analysis.
AB  - Until recently, studies of divergence and gene flow among closely-related taxa
      were generally limited to pairs of sister taxa. However, organisms frequently
      exchange genes with other non-sister taxa. The "northern oriole" group within
      genus Icterus exemplifies this problem. This group involves the extensively
      studied hybrid zone between Baltimore oriole (Icterus galbula) and Bullock's
      oriole (I. bullockii), an alleged hybrid zone between I. bullockii and black
      backed oriole (I. abeillei), and likely mtDNA introgression between I. galbula
      and I. abeillei. Here, we examine the divergence population genetics of the
      entire northern oriole group using a multipopulation Isolation-with-Migration
      (IM) model. In accordance with Haldane's rule, nuclear loci introgress
      extensively beyond the I. galbula-I. bullockii hybrid zone, while mtDNA does not.
      We found no evidence of introgression between I. bullockii and I. abeillei or
      between I. galbula and I. abeillei when all three species were analyzed together
      in a three-population model. However, traditional pairwise analysis suggested
      some nuclear introgression from I. abeillei into I. galbula, probably reflecting
      genetic contributions from I. bullockii unaccounted for in a two-population
      model. Thus, only by including all members of this group in the analysis was it
      possible to rigorously estimate the level of gene flow among these three closely
      related species.

PMID- 23145330
TI  - Evolutionary and biogeographic history of the subfamily Neoplecostominae
      (Siluriformes: Loricariidae).
AB  - Freshwater fish evolution has been shaped by changes in the earth's surface
      involving changes in the courses of rivers and fluctuations in sea level. The
      main objective of this study is to improve our knowledge of the evolution of
      loricariids, a numerous and adaptive group of freshwater catfish species, and the
      role of geological changes in their evolution. We use a number of different
      phylogenetic methods to test the relationships among 52 representative taxa
      within the Neoplecostominae using 4676 bps of mitochondrial and nuclear DNA. Our
      analysis revealed that the subfamily Neoplecostominae is monophyletic, including
      Pseudotocinclus, with three lineages recognized. The first lineage is composed of
      part of Pareiorhina rudolphi, P. cf. rudolphi, and Pseudotocinclus; the second is
      composed of Isbrueckerichthys, Pareiorhaphis, Kronichthys, and the species
      Neoplecostomus ribeirensis; and the third is composed of Pareiorhina carrancas,
      P. cf. carrancas, Pareiorhina sp. 1, a new genus, and all the species of the
      genus Neoplecostomus, except N. ribeirensis. The relaxed molecular clock
      calibration provides a temporal framework for the evolution of the group, which
      we use for a likelihood-based historical biogeographic analysis to test relevant
      hypotheses on the formation of southeast Brazil. We hypothesize that headwater
      capture events and marine regressions have shaped the patterns of distribution
      within the subfamily Neoplecostominae throughout the distinct basins of southeast
      Brazil.

PMID- 23145329
TI  - Phenotypic plasticity alone cannot explain climate-induced change in avian
      migration timing.
AB  - Recent climate change has been linked to shifts in the timing of life-cycle
      events in many organisms, but there is debate over the degree to which
      phenological changes are caused by evolved genetic responses of populations or by
      phenotypic plasticity of individuals. We estimated plasticity of spring arrival
      date in 27 species of bird that breed in the vicinity of an observatory in
      eastern North America. For 2441 individuals detected in multiple years, arrival
      occurred earlier during warm years, especially in species that migrate short
      distances. Phenotypic plasticity averaged -0.93 days  degrees C(-1) +/- 0.70 (95%
      CI). However, plasticity accounted for only 13-25% of the climate-induced trend
      in phenology observed over 46 years. Although our approach probably
      underestimates the full scope of plasticity, the data suggest that part of the
      response to environmental change has been caused by microevolution. The estimated
      evolutionary rates are plausible (0.016 haldanes).

PMID- 23145331
TI  - Higher temperature variability increases the impact of Batrachochytrium
      dendrobatidis and shifts interspecific interactions in tadpole mesocosms.
AB  - The emergence of amphibian chytridiomycosis, caused by the fungus
      Batrachochytrium dendrobatidis (Bd) has led to the decline and extinction of
      numerous amphibian species. Multiple studies have observed links between climatic
      factors and amphibian declines apparently caused by Bd. Using outdoor
      experimental mesocosms, we tested the response of red-legged frog (Rana aurora)
      tadpoles to increased variation in temperature, a component of climate linked to
      amphibian declines, and Bd exposure. We included tadpoles of a sympatric
      competitor species, Pacific chorus frog (Pseudacris regilla), in a fully
      factorial design to test the effects of Bd and temperature on interspecific
      interactions. We found that higher variation in temperature had numerous effects
      in mesocosms, including interacting with Bd presence to decrease the condition of
      R. aurora, shifting the relative performance of competing P. regilla and R.
      aurora, and accelerating the development of P. regilla relative to R. aurora. Our
      results demonstrate that increased variation in temperature can affect amphibians
      in multiple ways that will be contingent on ecological context, including the
      presence of Bd and competing species.

PMID- 23145332
TI  - Diversity protects plant communities against generalist molluscan herbivores.
AB  - Wildflower strips are used to increase natural enemies of crop pests and to
      conserve insect diversity on farmland. Mollusks, especially slugs, can affect the
      vegetation development in these strips considerably. Although recent theoretical
      work suggests that more diverse plant communities will exhibit greater resistance
      against herbivore pressure, empirical studies are scarce. We conducted a semi
      natural experiment in wildflower strips, manipulating trophic structure
      (reduction in herbivorous mollusks and reduction in major predators) and plant
      diversity (2, 6, 12, 20 and 24 sown species). This design allowed us to assess
      the effect of plant diversity, biomass and composition on mollusks, and vice
      versa, the effect of mollusc abundance on vegetation. Seven species of mollusks
      were found in the strips, with the slugs Arion lusitanicus, Deroceras reticulatum
      and Deroceras panormitanum being most frequent. We found a negative relationship
      between plant diversity and mollusk abundance, which was due predominantly to a
      decrease in the agricultural pest species A. lusitanicus. These results are
      consistent with the hypothesis that plant diversity can reduce the impact of
      herbivores. However, plant identity also had an effect on mollusks, and accounted
      for a much larger fraction of the variation in mollusk communities than
      biodiversity effects. While overall plant diversity decreased during the 3 years
      of the study, in the final year the highest plant diversity was found in the
      plots where mollusk populations were experimentally reduced. We conclude that
      selective feeding by generalist herbivores leads to changes in plant community
      composition and hence reduced plant diversity. Our results highlight the
      importance of plant biodiversity as protection against generalist herbivores,
      which if abundant can in the long term negatively impact plant diversity, driving
      the system along a "low plant diversity - high mollusk abundance" trajectory.

PMID- 23145333
TI  - Climate-change refugia in the sheltered bays of Palau: analogs of future reefs.
AB  - Coral bleaching and mortality are predicted to increase as climate change-induced
      thermal-stress events become more frequent. Although many studies document coral
      bleaching and mortality patterns, few studies have examined deviations from the
      expected positive relationships among thermal stress, coral bleaching, and coral
      mortality. This study examined the response of >30,000 coral colonies at 80 sites
      in Palau, during a regional thermal-stress event in 2010. We sought to determine
      the spatial and taxonomic nature of bleaching and examine whether any habitats
      were comparatively resistant to thermal stress. Bleaching was most severe in the
      northwestern lagoon, in accordance with satellite-derived maximum temperatures
      and anomalous temperatures above the long-term averages. Pocillopora populations
      suffered the most extensive bleaching and the highest mortality. However, in the
      bays where temperatures were higher than elsewhere, bleaching and mortality were
      low. The coral-community composition, constant exposure to high temperatures, and
      high vertical attenuation of light caused by naturally high suspended particulate
      matter buffered the corals in bays from the 2010 regional thermal-stress event.
      Yet, nearshore reefs are also most vulnerable to land-use change. Therefore,
      nearshore reefs should be given high conservation status because they provide
      refugia for coral populations as the oceans continue to warm.

PMID- 23145334
TI  - Gene expression divergence and nucleotide differentiation between males of
      different color morphs and mating strategies in the ruff.
AB  - By next generation transcriptome sequencing, it is possible to obtain data on
      both nucleotide sequence variation and gene expression. We have used this
      approach (RNA-Seq) to investigate the genetic basis for differences in plumage
      coloration and mating strategies in a non-model bird species, the ruff
      (Philomachus pugnax). Ruff males show enormous variation in the coloration of
      ornamental feathers, used for individual recognition. This polymorphism is linked
      to reproductive strategies, with dark males (Independents) defending territories
      on leks against other Independents, whereas white morphs (Satellites) co-occupy
      Independent's courts without agonistic interactions. Previous work found a strong
      genetic component for mating strategy, but the genes involved were not
      identified. We present feather transcriptome data of more than 6,000 de-novo
      sequenced ruff genes (although with limited coverage for many of them). None of
      the identified genes showed significant expression divergence between males, but
      many genetic markers showed nucleotide differentiation between different color
      morphs and mating strategies. These include several feather keratin genes,
      splicing factors, and the Xg blood-group gene. Many of the genes with significant
      genetic structure between mating strategies have not yet been annotated and their
      functions remain to be elucidated. We also conducted in-depth investigations of
      28 pre-identified coloration candidate genes. Two of these (EDNRB and TYR) were
      specifically expressed in black- and rust-colored males, respectively. We have
      demonstrated the utility of next generation transcriptome sequencing for
      identifying and genotyping large number of genetic markers in a non-model species
      without previous genomic resources, and highlight the potential of this approach
      for addressing the genetic basis of ecologically important variation.

PMID- 23145335
TI  - Genetic consequences of fragmentation in "arbor vitae," eastern white cedar
      (Thuja occidentalis L.), toward the northern limit of its distribution range.
AB  - We tested the hypothesis that marginal fragmented populations of eastern white
      cedar (EWC) are genetically isolated due to reduced pollen and gene flow. In
      accordance with the central-marginal model, we predicted a decrease in population
      genetic diversity and an increase in differentiation along the latitudinal
      gradient from the boreal mixed-wood to northern coniferous forest. A total of 24
      eastern white cedar populations were sampled along the north-south latitudinal
      gradient for microsatellite genotyping analysis. Positive F(is) values and
      heterozygote deficiency were observed in populations from the marginal (F(is) =
      0.244; P(HW) = 0.0042) and discontinuous zones (F(is) = 0.166; P(HW) = 0.0042).
      However, populations from the continuous zone were in HW equilibrium (F(is) = 
      0.007; P(HW) = 0.3625). There were no significant latitudinal effects on gene
      diversity (H(s)), allelic richness (AR), or population differentiation (F(st)).
      Bayesian and NJT (neighbor-joining tree) analyses demonstrated the presence of a
      population structure that was partly consistent with the geographic origins of
      the populations. The impact of population fragmentation on the genetic structure
      of EWC is to create a positive inbreeding coefficient, which was two to three
      times higher on average than that of a population from the continuous zone. This
      result indicated a higher occurrence of selfing within fragmented EWC populations
      coupled with a higher degree of gene exchange among near-neighbor relatives,
      thereby leading to significant inbreeding. Increased population isolation was
      apparently not correlated with a detectable effect on genetic diversity. Overall,
      the fragmented populations of EWC appear well-buffered against effects of
      inbreeding on genetic erosion.

PMID- 23145336
TI  - Bacteriocin-mediated interactions within and between coexisting species.
AB  - Bacteriocins are bacteriocidal toxins released by almost all bacteria. They are
      thought to have a narrow range of killing, but as bacteriocin-mediated
      interactions have been rarely studied at biologically relevant scales, whether
      this narrow range of action falls mostly within or mostly between coexisting
      species in natural communities is an open question with important ecological and
      evolutionary implications. In a previous study, we systematically sampled
      Xenorhabdus bacteria along a hillside and found evidence for genotypic
      variability and bacteriocin-mediated interactions within Xenorhabdus bovienii and
      X. koppenhoeferi colonies that were collected only a few meters apart. In
      contrast, colonies that were isolated from the same soil sample were always
      genetically similar and showed no inhibitions. Here, we conducted pairwise growth
      inhibition assays within and between seven X. bovienii and five X. koppenhoeferi
      colonies that were isolated from different soil samples; all seven X. bovienii
      colonies and at least three of the X. koppenhoeferi have been distinguished as
      distinct genotypes based on coarse-grain genomic markers. We found signatures for
      both conspecific and heterospecific bacteriocin inhibitions in this natural
      community of Xenorhabdus bacteria, but intraspecific inhibitions were
      significantly more common than interspecific inhibitions. These results suggest
      that bacteriocins have a major role in intraspecific competition in nature, but
      also suggest that bacterocins are important in mediating interspecific
      interactions among coexisting species in natural communities.

PMID- 23145337
TI  - Male pheromone polymorphism and reproductive isolation in populations of
      Drosophila simulans.
AB  - The dominant cuticular hydrocarbons (HC) in Drosophila simulans are 7-tricosene
      (7-T) and 7-pentacosene (7-P). The 7-T is the major HC in East Africa and in
      other continents. In West Africa, D. simulans is very rare and displays 7-P as
      the major compound. We studied three D. simulans strains from Egypt (Eg), Sao
      Tome (ST), and Cameroon (Cam), with 7-T, intermediary or 7-P phenotypes. HC
      profiles of ST and Cam female differed slightly from corresponding male profiles;
      females had more 7-T and less 7-P. Varying temperature affected all HCs (even
      those with 27 and 29 carbons)-not just 7-T and 7-P; there was no clear
      relationship between HC phenotype and resistance to desiccation. We report
      reproductive isolation between Eg and ST and Eg and Cam (but not between ST and
      Cam), which is due to Eg and Cam female preferences for their own males. In
      conclusion, our findings do support divergence of D. simulans populations from
      West Africa for both pheromonal profile and mating preference.

PMID- 23145338
TI  - The origins of Atlantic salmon (Salmo salar L.) recolonizing the River Mersey in
      northwest England.
AB  - By the 1950s, pollution had extirpated Atlantic salmon in the river Mersey in
      northwest England. During the 1970s, an extensive restoration program began and
      in 2001, an adult salmon was caught ascending the river. Subsequently, a fish
      trap was installed and additional adults are now routinely sampled. In this
      study, we have genotyped 138 adults and one juvenile salmon at 14 microsatellite
      loci from across this time period (2001-2011). We have used assignment analysis
      with a recently compiled pan-European microsatellite baseline to identify their
      most probable region of origin. Fish entering the Mersey appear to originate from
      multiple sources, with the greatest proportion (45-60%, dependent on methodology)
      assigning to rivers in the geographical region just north of the Mersey, which
      includes Northwest England and the Solway Firth. Substantial numbers also appear
      to originate from rivers in western Scotland, and from rivers in Wales and
      Southwest England; nonetheless, the number of fish originating from proximal
      rivers to the west of the Mersey was lower than expected. Our results suggest
      that the majority of salmon sampled in the Mersey are straying in a southerly
      direction, in accordance with the predominantly clockwise gyre present in the
      eastern Irish Sea. Our findings highlight the complementary roles of improving
      water quality and in-river navigability in restoring salmon to a river and
      underlines further the potential benefits of restoration over stocking as a long
      term solution to declining fish stocks.

PMID- 23145339
TI  - Global remote sensing of water-chlorophyll ratio in terrestrial plant leaves.
AB  - I evaluated the use of global remote sensing techniques for estimating plant leaf
      chlorophyll a + b (C(ab); MUg cm(-2)) and water (C(w); mg cm(-2)) concentrations
      as well as the ratio of C(w)/C(ab) with the PROSAIL model under possible
      distributions for leaf and soil spectra, leaf area index (LAI), canopy geometric
      structure, and leaf size. First, I estimated LAI from the normalized difference
      vegetation index. I found that, at LAI values <2, C(ab), C(w), and C(w)/C(ab)
      could not be reliably estimated. At LAI values >2, C(ab) and C(w) could be
      estimated for only restricted ranges of the canopy structure; however, the ratio
      of C(w)/C(ab) could be reliably estimated for a variety of possible canopy
      structures with coefficients of determination (R(2)) ranging from 0.56 to 0.90.
      The remote estimation of the C(w)/C(ab) ratio from satellites offers information
      on plant condition at a global scale.

PMID- 23145340
TI  - Intracoastal shipping drives patterns of regional population expansion by an
      invasive marine invertebrate.
AB  - Understanding the factors contributing to expansion of nonnative populations is a
      critical step toward accurate risk assessment and effective management of
      biological invasions. Nevertheless, few studies have attempted explicitly to test
      hypotheses regarding factors driving invasive spread by seeking correlations
      between patterns of vector movement and patterns of genetic connectivity. Herein,
      we describe such an attempt for the invasive tunicate Styela clava in the
      northeastern Pacific. We utilized microsatellite data to estimate gene flow
      between samples collected throughout the known range of S. clava in the region,
      and assessed correlation of these estimates with patterns of intracoastal
      commercial vessel traffic. Our results suggest that recent shipping patterns have
      contributed to the contemporary distribution of genetic variation. However, the
      analysis also indicates that other factors-including a complex invasion history
      and the influence of other vectors-have partially obscured genetic patterns
      associated with intracoastal population expansion.

PMID- 23145341
TI  - Stressful environments induce novel phenotypic variation: hierarchical reaction
      norms for sperm performance of a pervasive invader.
AB  - Genetic variation for phenotypic plasticity is ubiquitous and important. However,
      the scale of such variation including the relative variability present in
      reaction norms among different hierarchies of biological organization (e.g.,
      individuals, populations, and closely related species) is unknown. Complicating
      interpretation is a trade-off in environmental scale. As plasticity can only be
      inferred over the range of environments tested, experiments focusing on fine
      tuned responses to normal or benign conditions may miss cryptic phenotypic
      variation expressed under novel or stressful environments. Here, we sought to
      discern the presence and shape of plasticity in the performance of brown trout
      sperm as a function of optimal to extremely stressful river pH, and demarcate if
      the reaction norm varies among genotypes. Our overarching goal was to determine
      if deteriorating environmental quality increases expressed variation among
      individuals. A more applied aim was to ascertain whether maintaining sperm
      performance over a wide pH range could help explain how brown trout are able to
      invade diverse river systems when transplanted outside of their native range.
      Individuals differed in their reaction norms of phenotypic expression of an
      important trait in response to environmental change. Cryptic variation was
      revealed under stressful conditions, evidenced through increasing among
      individual variability. Importantly, data on population averages masked this
      variability in plasticity. In addition, canalized reaction norms in sperm
      swimming velocities of many individuals over a very large range in water
      chemistry may help explain why brown trout are able to colonize a wide variety of
      habitats.

PMID- 23145342
TI  - A mate to die for? A model of conditional monogyny in cannibalistic spiders.
AB  - Monogynous males in various species actively limit themselves to mating with a
      single female in their lifetime. Whereas previous models have considered monogyny
      as an obligate mating strategy, here we explore the potential of monogyny to
      evolve as a context-specific (conditional) behavior. Using a state-dependent
      dynamic game model based on the biology of the cannibalistic spider Argiope
      bruennichi, we confirm that conditional monogyny can evolve under broad
      conditions, including an even sex ratio. We predict that males should make a
      terminal investment when mating with large, virgin females, especially if
      population density is low and the encounter occurs late in the season. We
      encourage empirical tests for the existence of conditional monogyny in all
      species where monogyny occurs in the absence of strict morphological constraints
      that would make it obligatory.

PMID- 23145343
TI  - Extensive genetic diversity and rapid population differentiation during blooms of
      Alexandrium fundyense (Dinophyceae) in an isolated salt pond on Cape Cod, MA,
      USA.
AB  - In Massachusetts, paralytic shellfish poisoning (PSP) is annually recurrent along
      the coastline, including within several small embayments on Cape Cod. One such
      system, the Nauset Marsh System (NMS), supports extensive marshes and a thriving
      shellfishing industry. Over the last decade, PSP in the NMS has grown
      significantly worse; however, the origins and dynamics of the toxic Alexandrium
      fundyense (Balech) populations that bloom within the NMS are not well known. This
      study examined a collection of 412 strains isolated from the NMS and the Gulf of
      Maine (GOM) in 2006-2007 to investigate the genetic characteristics of localized
      blooms and assess connectivity with coastal populations. Comparisons of genetic
      differentiation showed that A. fundyense blooms in the NMS exhibited extensive
      clonal diversity and were genetically distinct from populations in the GOM. In
      both project years, genetic differentiation was observed among temporal samples
      collected from the NMS, sometimes occurring on the order of approximately 7 days.
      The underlying reasons for temporal differentiation are unknown, but may be due,
      in part, to life-cycle characteristics unique to the populations in shallow
      embayments, or possibly driven by selection from parasitism and zooplankton
      grazing; these results highlight the need to investigate the role of selective
      forces in the genetic dynamics of bloom populations. The small geographic scale
      and limited connectivity of NMS salt ponds provide a novel system for
      investigating regulators of blooms, as well as the influence of selective forces
      on population structure, all of which are otherwise difficult or impossible to
      study in the adjacent open-coastal waters or within larger estuaries.

PMID- 23145344
TI  - Large-scale longitudinal gradients of genetic diversity: a meta-analysis across
      six phyla in the Mediterranean basin.
AB  - Biodiversity is the diversity of life at all scales, from genes to ecosystems.
      Predicting its patterns of variation across the globe is a fundamental issue in
      ecology and evolution. Diversity within species, that is, genetic diversity, is
      of prime importance for understanding past and present evolutionary patterns, and
      highlighting areas where conservation might be a priority. Using published data
      on the genetic diversity of species whose populations occur in the Mediterranean
      basin, we calculated a coefficient of correlation between within-population
      genetic diversity indices and longitude. Using a meta-analysis framework, we
      estimated the role of biological, ecological, biogeographic, and marker type
      factors on the strength and magnitude of this correlation in six phylla. Overall,
      genetic diversity increases from west to east in the Mediterranean basin. This
      correlation is significant for both animals and plants, but is not uniformly
      expressed for all groups. It is stronger in the southern than in the northern
      Mediterranean, in true Mediterranean plants than in plants found at higher
      elevations, in trees than in other plants, and in bi-parentally and paternally
      than in maternally inherited DNA makers. Overall, this correlation between
      genetic diversity and longitude, and its patterns across biological and
      ecological traits, suggests the role of two non-mutually exclusive major
      processes that shaped the genetic diversity in the Mediterranean during and after
      the cold periods of the Pleistocene: east-west recolonization during the Holocene
      and population size contraction under local Last Glacial Maximum climate in
      resident western and low elevation Mediterranean populations.

PMID- 23145345
TI  - Little effect of seasonal constraints on population genetic structure in eusocial
      paper wasps.
AB  - Climate has long been suggested to affect population genetic structures of
      eusocial insect societies. For instance, Hamilton [Journal of Theoretical
      Biology7 (1964) 17] discusses whether temperate and tropical eusocial insects may
      show differences in population-level genetic structure and viscosity, and how
      this might relate to differences in the degree of synchrony in their life cycles
      or modes of nest founding. Despite the importance of Hamilton's 1964 papers, this
      specific idea has not been tested in actual populations of wasps, probably due to
      the paucity of studies on tropical species. Here, we compare colony and
      population genetic structures in two species of primitively eusocial paper wasps
      with contrasting ecologies: the tropical species Polistes canadensis and the
      temperate species P. dominulus. Our results provide important clarifications of
      Hamilton's discussion. Specifically, we show that the genetic structures of the
      temperate and tropical species were very similar, indicating that seasonality
      does not greatly affect population viscosity or inbreeding. For both species, the
      high genetic differentiation between nests suggests strong selection at the nest
      level to live with relatives, whereas low population viscosity and low genetic
      differentiation between nest aggregations might reflect balancing selection to
      disperse, avoiding competition with relatives. Overall, our study suggests no
      prevalence of seasonal constraints of the life cycle in affecting the population
      genetic structure of eusocial paper wasps. These conclusions are likely to apply
      also to other primitively eusocial insects, such as halictine bees. They also
      highlight how selection for a kin structure that promotes altruism can override
      potential effects of ecology in eusocial insects.

PMID- 23145346
TI  - Effects of CO(2) enrichment on photosynthesis, growth, and nitrogen metabolism of
      the seagrass Zostera noltii.
AB  - Seagrass ecosystems are expected to benefit from the global increase in CO(2) in
      the ocean because the photosynthetic rate of these plants may be C(i)-limited at
      the current CO(2) level. As well, it is expected that lower external pH will
      facilitate the nitrate uptake of seagrasses if nitrate is cotransported with H(+)
      across the membrane as in terrestrial plants. Here, we investigate the effects of
      CO(2) enrichment on both carbon and nitrogen metabolism of the seagrass Zostera
      noltii in a mesocosm experiment where plants were exposed for 5 months to two
      experimental CO(2) concentrations (360 and 700 ppm). Both the maximum
      photosynthetic rate (P(m)) and photosynthetic efficiency (alpha) were higher (1.3
      and 4.1-fold, respectively) in plants exposed to CO(2)-enriched conditions. On
      the other hand, no significant effects of CO(2) enrichment on leaf growth rates
      were observed, probably due to nitrogen limitation as revealed by the low
      nitrogen content of leaves. The leaf ammonium uptake rate and glutamine
      synthetase activity were not significantly affected by increased CO(2)
      concentrations. On the other hand, the leaf nitrate uptake rate of plants exposed
      to CO(2)-enriched conditions was fourfold lower than the uptake of plants exposed
      to current CO(2) level, suggesting that in the seagrass Z. noltii nitrate is not
      cotransported with H(+) as in terrestrial plants. In contrast, the activity of
      nitrate reductase was threefold higher in plant leaves grown at high-CO(2)
      concentrations. Our results suggest that the global effects of CO(2) on seagrass
      production may be spatially heterogeneous and depend on the specific nitrogen
      availability of each system. Under a CO(2) increase scenario, the natural levels
      of nutrients will probably become limiting for Z. noltii. This potential
      limitation becomes more relevant because the expected positive effect of CO(2)
      increase on nitrate uptake rate was not confirmed.

PMID- 23145349
TI  - Live imaging of individual cell divisions in mouse neuroepithelium shows
      asymmetry in cilium formation and Sonic hedgehog response.
AB  - BACKGROUND: Primary cilia are microtubule-based sensory organelles that play
      important roles in developmental signaling pathways. Recent work demonstrated
      that, in cell culture, the daughter cell that inherits the older mother centriole
      generates a primary cilium and responds to external stimuli prior to its sister
      cell. This asynchrony in timing of cilia formation could be especially critical
      during development as cell divisions are required for both differentiation and
      maintenance of progenitor cell niches. METHODS: Here we integrate several
      fluorescent markers and use ex vivo live imaging of a single cell division within
      the mouse E8.5 neuroepithelium to reveal both the formation of a primary cilium
      and the transcriptional response to Sonic hedgehog in the daughter cells.
      RESULTS: We show that, upon cell division, cilia formation and the Sonic hedgehog
      response are asynchronous between the daughter cells. CONCLUSIONS: Our results
      demonstrate that we can directly observe single cell divisions within the
      developing neuroepithelium and concomitantly monitor cilium formation or Sonic
      hedgehog response. We expect this method to be especially powerful in examining
      whether cellular behavior can lead to both differentiation and maintenance of
      cells in a progenitor niche.

PMID- 23145350
TI  - Secondary stressors and extreme events and disasters: a systematic review of
      primary research from 2010-2011.
AB  - Introduction Extreme events and disasters, such as earthquakes and floods, cause
      distress and are associated with some people developing mental disorders. Primary
      stressors inherent in many disasters can include injuries sustained or watching
      someone die. The literature recognises the distress which primary stressors cause
      and their association with mental disorders. Secondary stressors such as a lack
      of financial assistance, the gruelling process of submitting an insurance claim,
      parents' worries about their children, and continued lack of infrastructure can
      manifest their effects shortly after a disaster and persist for extended periods
      of time. Secondary stressors, and their roles in affecting people's longer-term
      mental health, should not be overlooked. We draw attention in this review to the
      nature of secondary stressors that are commonly identified in the literature,
      assess how they are measured, and develop a typology of these stressors that
      often affect people after extreme events. Methods We searched for relevant papers
      from 2010 and 2011 using MEDLINE(r), Embase and PsycINFO(r). We selected primary
      research papers that evaluated the associations between secondary stressors and
      distress or mental disorders following extreme events, and were published in
      English. We extracted information on which secondary stressors were assessed, and
      used thematic analysis to group the secondary stressors into a typology. Results
      Thirty-two relevant articles published in 2010 and 2011 were identified. Many
      secondary stressors were poorly defined and difficult to differentiate from
      primary stressors or other life events. We identified 11 categories of secondary
      stressors, though some extend over more than one category. The categories
      include: economic stressors such as problems with compensation, recovery of and
      rebuilding homes; loss of physical possessions and resources; health-related
      stressors; stress relating to education and schooling; stress arising from media
      reporting; family and social stressors; stress arising from loss of leisure and
      recreation; and stress related to changes in people's views of the world or
      themselves. Limitations in this review include its focus on studies published in
      2010 and 2011, which may have led to some secondary stressors being excluded.
      Assumptions have been made about whether certain items are secondary stressors,
      if unclear definitions made it difficult to differentiate them from primary
      stressors. Conclusions This is the first review, to our knowledge, that has
      developed a typology of secondary stressors that occur following extreme events.
      We discuss the differing natures of these stressors and the criteria that should
      be used to differentiate primary and secondary stressors. Some secondary
      stressors, for example, are entities in themselves, while others are persisting
      primary stressors that exert their effects through failure of societal responses
      to disasters to mitigate their immediate impacts. Future research should aim to
      define secondary stressors and investigate the interactions between stressors.
      This is essential if we are to identify which secondary stressors are amenable to
      interventions which might reduce their impacts on the psychosocial resilience and
      mental health of people who are affected by disasters. Corresponding Author: Dr
      Sarah Lock, Extreme Events and Health Protection, London, 151 Buckingham Palace
      Road, London, SW1W 9SZ. E-mail: sarah.lock@hpa.org.uk.

PMID- 23145351
TI  - Health impacts of wildfires.
AB  - Introduction Wildfires are common globally. Although there has been considerable
      work done on the health effects of wildfires in countries such as the USA where
      they occur frequently there has been relatively little work to investigate health
      effects in the United Kingdom. Climate change may increase the risk of increasing
      wildfire frequency, therefore there is an urgent need to further understand the
      health effects and public awareness of wildfires. This study was designed to
      review current evidence about the health effects of wildfires from the UK
      standpoint. Methods A comprehensive literature review of international evidence
      regarding wildfire related health effects was conducted in January 2012. Further
      information was gathered from authors' focus groups. Results A review of the
      published evidence shows that human health can be severely affected by wildfires.
      Certain populations are particularly vulnerable. Wood smoke has high levels of
      particulate matter and toxins. Respiratory morbidity predominates, but
      cardiovascular, ophthalmic and psychiatric problems can also result. In addition
      severe burns resulting from direct contact with the fire require care in special
      units and carry a risk of multi - organ complications. The wider health
      implications from spreading air, water and land pollution are of concern. Access
      to affected areas and communication with populations living within them is
      crucial in mitigating risk. Conclusion This study has identified factors that may
      reduce public health risk from wildfires. However more research is needed to
      evaluate longer term health effects from wildfires. An understanding of such
      factors is vital to ensure preparedness within health care services for such
      events.

PMID- 23145348
TI  - Chemistry with spatial control using particles and streams().
AB  - Spatial control of chemical reactions, with micro- and nanometer scale
      resolution, has important consequences for one pot synthesis, engineering complex
      reactions, developmental biology, cellular biochemistry and emergent behavior. We
      review synthetic methods to engineer this spatial control using chemical
      diffusion from spherical particles, shells and polyhedra. We discuss systems that
      enable both isotropic and anisotropic chemical release from isolated and arrayed
      particles to create inhomogeneous and spatially patterned chemical fields. In
      addition to such finite chemical sources, we also discuss spatial control enabled
      with laminar flow in 2D and 3D microfluidic networks. Throughout the paper, we
      highlight applications of spatially controlled chemistry in chemical kinetics,
      reaction-diffusion systems, chemotaxis and morphogenesis.

PMID- 23145352
TI  - Repeat triage in disaster relief: questions from haiti.
AB  - During a mass casualty disaster, the acute imbalance between need for treatment
      and capacity to supply care poses difficult rationing problems. It is common to
      assume that such disasters call for "utilitarian" procedures that deliberately
      prioritize saving the most lives over other considerations. A group of medical
      responders to the 2010 Haitian earthquake faced particular challenges in
      determining how to allocate limited treatment, time and other resources between
      existing patients and potential patients not yet under care. We identified that
      rationing dilemmas points occurred at three points: when care had to be limited,
      when care had to be completed prematurely, and when care had to be withdrawn.
      "Repeat triage" refers to rationing challenges occurring at all these points,
      where the allocation of care is between existing and potential patients. By
      contrast, "initial triage" designates the allocation of access to treatment among
      new arrivals, all of whom are potential patients. Repeat and initial triage
      differ significantly. Several considerations make repeat triage special by
      supporting limited priority to existing patients, in transgression of pure
      "utilitarian" procedures: (1) Pragmatically, often it is more efficient to
      complete treatment on existing patients, for whom prognosis can be established
      with greater certainty and without added time, than to attempt to save new
      patients; (2) A fiduciary trust relationship has been formed between care-giver
      and existing patients, which may make the moral obligation towards them somewhat
      stronger than the one to potential patients; (3) Existing patients will have
      often arrived earlier, so when needs are equal, the "first come, first served"
      principle prioritizes them for care; (4) Withdrawal of care during repeat triage
      may constitute active rather than passive harm, and more often a serious
      transgression of patient autonomy; (5) Health providers should normally not be
      asked to behave in ways that profoundly violate their personal and professional
      integrity, and abandoning existing patients may do so. For these reasons,
      responders can permissibly give a degree of priority to existing patients over
      newcomers in disaster.

PMID- 23145353
TI  - The effects of glucocorticoid and voluntary exercise treatment on the development
      of thoracolumbar kyphosis in dystrophin-deficient mice.
AB  - The development of spinal curvature deformities is a hallmark of muscular
      dystrophy. While glucocorticoid treatment has been shown to prolong muscle
      function in dystrophic mice, its effects on the development of dystrophinopathic
      spinal deformation are poorly understood. In this study, we test the effects of
      glucocorticoid treatment on the onset of thoracolumbar kyphosis in the dystrophin
      deficient mdx mouse using voluntary running exercise to exacerbate muscle
      fibrosis. We measure the kyphotic index, erector spinae muscle fibrosis, and
      vertebral bone histomorphometry in 4-month-old mdx mice in four groups: sedentary
      control, exercise-treated (continuous voluntary access to an activity wheel),
      glucocorticoid-treated, and glucocorticoid + exercise-treated. Exercise treated
      mice were found to have significantly lower kyphotic index (i.e., greater
      kyphosis) and greater muscle fibrosis relative to controls (p < 0.05). However,
      the deleterious effect of exercise on KI and muscle fibrosis was prevented by
      glucocorticoid treatment. Some differences in bone histological parameters were
      observed between treatment groups, suggesting there is a complex relationship
      between dystrophic muscular changes and vertebral bone mass. Our findings
      indicate glucocorticoid treatment delays the onset of thoracodorsal spinal
      deformation in mdx mice.

PMID- 23145354
TI  - The C2A domain in dysferlin is important for association with MG53 (TRIM72).
AB  - In skeletal muscle, Mitsugumin 53 (MG53), also known as muscle-specific
      tripartite motif 72, reportedly interacts with dysferlin to regulate membrane
      repair. To better understand the interactions between dysferlin and MG53, we
      conducted immunoprecipitation (IP) and pull-down assays. Based on IP assays, the
      C2A domain in dysferlin associated with MG53. MG53 reportedly exists as a
      monomer, a homodimer, or an oligomer, depending on the redox state. Based on pull
      down assays, wild-type dysferlin associated with MG53 dimers in a Ca2+-dependent
      manner, but MG53 oligomers associated with both wild-type and C2A-mutant
      dysferlin in a Ca2+-independent manner. In pull-down assays, a pathogenic
      missense mutation in the C2A domain (W52R-C2A) inhibited the association between
      dysferlin and MG53 dimers, but another missense mutation (V67D-C2A) altered the
      calcium sensitivity of the association between the C2A domain and MG53 dimers. In
      contrast to the multimers, the MG53 monomers did not interact with wild-type or
      C2A mutant dysferlin in pull-down assays. These results indicated that the C2A
      domain in dysferlin is important for the Ca2+-dependent association with MG53
      dimers and that dysferlin may associate with MG53 dimers in response to the
      influx of Ca2+ that occurs during membrane injury. To examine the biological role
      of the association between dysferlin and MG53, we co-expressed EGFP-dysferlin
      with RFP-tagged wild-type MG53 or RFP-tagged mutant MG53 (RFP-C242A-MG53) in
      mouse skeletal muscle, and observed molecular behavior during sarcolemmal repair;
      it has been reported that the C242A-MG53 mutant forms dimers, but not oligomers.
      In response to membrane wounding, dysferlin accumulated at the injury site within
      1 second; this dysferlin accumulation was followed by the accumulation of wild
      type MG53. However, accumulation of RFP-C242A MG53 at the wounded site was
      impaired relative to that of RFP-wild-type MG53. Co-transfection of RFP-C242A
      MG53 inhibited the recruitment of dysferlin to the sarcolemmal injury site. We
      also examined the molecular behavior of GFP-wild-type MG53 during sarcolemmal
      repair in dysferlin-deficient mice which show progressive muscular dystrophy, and
      found that GFP-MG53 accumulated at the wound similar to wild-type mice. Our data
      indicate that the coordination between dysferlin and MG53 plays an important role
      in efficient sarcolemmal repair.

PMID- 23145355
TI  - Pitfalls in the detection of cholesterol in Huntington's disease models.
AB  - Background Abnormalities in brain cholesterol homeostasis have been reported in
      Huntington's disease (HD), an adult-onset neurodegenerative disorder caused by an
      expansion in the number of CAG repeats in the huntingtin (HTT) gene. However, the
      results have been contradictory with respect to whether cholesterol levels
      increase or decrease in HD models. Biochemical and mass spectrometry methods show
      reduced levels of cholesterol precursors and cholesterol in HD cells and in the
      brains of several HD animal models. Abnormal brain cholesterol homeostasis was
      also inferred from studies in HD patients. In contrast, colorimetric and
      enzymatic methods indicate cholesterol accumulation in HD cells and tissues. Here
      we used several methods to investigate cholesterol levels in cultured cells in
      the presence or absence of mutant HTT protein. Results Colorimetric and enzymatic
      methods with low sensitivity gave variable results, whereas results from a
      sensitive analytical method, gas chromatography-mass spectrometry, were more
      reliable. Sample preparation, high cell density and cell clonality also
      influenced the detection of intracellular cholesterol. Conclusions Detection of
      cholesterol in HD samples by colorimetric and enzymatic assays should be
      supplemented by detection using more sensitive analytical methods. Care must be
      taken to prepare the sample appropriately. By evaluating lathosterol levels using
      isotopic dilution mass spectrometry, we confirmed reduced cholesterol
      biosynthesis in knock-in cells expressing the polyQ mutation in a constitutive or
      inducible manner. *Correspondence should be addressed to Elena Cattaneo:
      elena.cattaneo@unimi.it.

PMID- 23145356
TI  - "Now I see a brighter day": expectations and perceived benefits of an Iyengar
      yoga intervention for young patients with rheumatoid arthritis.
AB  - Rheumatoid arthritis (RA) is a chronic disease characterized by inflammation of
      joints and associated fatigue, deteriorated range of motion, and impaired
      psychosocial functioning. Young adults with RA are at a particular risk for
      compromised health-related quality of life, and there is a need for safe,
      effective complementary treatment in addition to traditional medical approaches.
      The aim of the present study was to use face-to-face participant interviews,
      conducted before and after an Iyengar yoga (IY) program, to examine mechanisms
      through which yoga may be beneficial to young adults with RA.This pilot study
      utilized a single-arm design where all participants received the intervention.
      Classes were taught twice per week (1.5 hours each) for 6 weeks by an IY teacher
      qualified in therapeutics. Interview themes included participants' baseline
      expectations about yoga and viewpoints as to how their functioning had been
      impacted by the IY intervention were examined. Five young adults with RA aged 24
      31 years (mean = 28; 80% female) completed the yoga intervention. Participants
      consistently reported that yoga helped with energy, relaxation and mood and they
      discussed perceived mechanisms for how yoga impacted well-being. Mechanisms
      included physical changes such as range of motion and physiological awareness,
      and psychospiritual developments such as acceptance, coping, self-efficacy and
      mindfulness. Though the study is limited, participants' responses provide
      compelling evidence that IY for RA patients is an intervention worthy of further
      exploration. The mechanisms and outcomes reported by participants support a
      biopsychosocial model, which proposes that yoga benefits patients through both
      physiological and psychospiritual changes.

PMID- 23145357
TI  - Dual tracer imaging of SPECT and PET probes in living mice using a sequential
      protocol.
AB  - Over the past 20 years, multimodal imaging strategies have motivated the fusion
      of Positron Emission Tomography (PET) or Single Photon Emission Computed
      Tomography (SPECT) scans with an X-ray computed tomography (CT) image to provide
      anatomical information, as well as a framework with which molecular and
      functional images may be co-registered. Recently, pre-clinical nuclear imaging
      technology has evolved to capture multiple SPECT or multiple PET tracers to
      further enhance the information content gathered within an imaging experiment.
      However, the use of SPECT and PET probes together, in the same animal, has
      remained a challenge. Here we describe a straightforward method using an
      integrated trimodal imaging system and a sequential dosing/acquisition protocol
      to achieve dual tracer imaging with (99m)Tc and (18)F isotopes, along with
      anatomical CT, on an individual specimen. Dosing and imaging is completed so that
      minimal animal manipulations are required, full trimodal fusion is conserved, and
      tracer crosstalk including down-scatter of the PET tracer in SPECT mode is
      avoided. This technique will enhance the ability of preclinical researchers to
      detect multiple disease targets and perform functional, molecular, and anatomical
      imaging on individual specimens to increase the information content gathered
      within longitudinal in vivo studies.

PMID- 23145358
TI  - Ready for prime time? Dual tracer PET and SPECT imaging.
AB  - Dual isotope single photon emission computed tomography (SPECT) and dual tracer
      positron emission tomography (PET) imaging have great potential in clinical and
      molecular applications in the pediatric as well as the adult populations in many
      areas of brain, cardiac, and oncologic imaging as it allows the exploration of
      different physiological and molecular functions (e.g., perfusion,
      neurotransmission, metabolism, apoptosis, angiogenesis) under the same
      physiological and physical conditions. This is crucial when the physiological
      functions studied depend on each other (e.g., perfusion and metabolism) hence
      requiring simultaneous assessment under identical conditions, and can reduce
      greatly the quantitation errors associated with physical factors that can change
      between acquisitions (e.g., human subject or animal motion, change in the
      attenuation map as a function of time) as is detailed in this editorial. The
      clinical potential of simultaneous dual isotope SPECT, dual tracer PET and dual
      SPECT/PET imaging are explored and summarized. In this issue of AJNMMI
      (http://www.ajnmmi.us), Chapman et al. explore the feasibility of simultaneous
      and sequential SPECT/PET imaging and conclude that down-scatter and crosstalk
      from 511 keV photons preclude obtaining useful SPECT information in the presence
      of PET radiotracers. They report on an alternative strategy that consists of
      performing sequential SPECT and PET studies in hybrid microPET/SPECT/CT scanners,
      now widely available for molecular imaging. They validate their approach in a
      phantom consisting of a 96-well plate with variable (99m)Tc and (18)F
      concentrations and illustrate the utility of such approaches in two sequential
      SPECT-PET/CT studies that include (99m)Tc-MAA/(18)F-NaF and (99m)Tc
      Pentetate/(18)F-NaF. These approaches will need to be proven reproducible,
      accurate and robust to variations in the experimental conditions before they can
      be accepted by the molecular imaging community and be implemented in routine
      molecular microPET and microSPECT explorations. Although currently not accepted
      as standard procedures in the molecular imaging community, such approaches have
      the potential to open the way to new SPECT/PET explorations that allow studying
      molecular mechanisms and pathways in the living animal under similar
      physiological conditions. Although still premature for the clinical setting,
      these approaches can be extended to clinical research once proven accurate and
      precise in vivo in small and large animal models.

PMID- 23145359
TI  - Non-invasive imaging of PI3K/Akt/mTOR signalling in cancer.
AB  - Platinum based drugs are widely used to treat various types of cancers by
      inducing DNA damage mediated cytotoxicity. However, acquirement of
      chemoresistance towards platinum based drugs is a common phenomenon and a major
      hurdle in combating the relapse of the disease. Oncogenesis and chemoresistance
      are multifactorial maladies which often involve deregulation of one of the prime
      cell survival pathways, the PI3K/Akt/mTOR signalling cascade. The genetic
      alterations related to this pathway are often responsible for initiation and/or
      maintenance of carcinogenesis. Molecular components of this pathway are long
      being recognized as major targets for therapeutic intervention and are now also
      have emerged as potential tools for diagnosis of cancer. To develop novel
      therapeutics against the key molecules of PI3K pathway, stringent validation is
      required using both in-vitro and in-vivo models. Repetitive and non-invasive
      molecular imaging techniques, a relatively recent field in biomedical imaging
      hold great promises for monitoring such diagnosis and therapy. In this review, we
      first introduced the PI3K/Akt/mTOR pathway and its role in acquirement of
      chemoresistance in various cancers. Further we described how non-invasive
      molecular imaging approaches are sought to use this PI3K signalling axis for the
      therapeutics and diagnosis. A theranostic approach using various imaging
      modalities should be the future of PI3K signalling based drug development
      venture.

PMID- 23145361
TI  - (18)F-Deoxyglucose (FDG) kinetics evaluated by a non-compartment model based on a
      linear regression function using a computer based simulation: correlation with
      the parameters of the two-tissue compartment model.
AB  - Parametric imaging with a linear regression function of the tracer activity curve
      fit is a non-compartmental method, which can be used for the evaluation of
      dynamic PET (dPET) studies. However, the dependency of the slope of the
      regression function fit on the (18)F-Deoxyglucose (FDG) 2-tissue compartment
      parameters (vb, k1-k4) is not known yet. This study is focused on the impact of
      the 2-tissue compartment parameters on the slope of the curve. A data base of
      1760 dynamic PET FDG studies with the corresponding 2-tissue compartment model
      parameter solutions were available and used to calculate synthetic time-activity
      data based on the 2-tissue compartment model. The input curve was calculated from
      the median values of the input curves of the 1760 dynamic data sets. Then,
      sequentially each of the five parameters (vb, k1-k4) of the 2-tissue compartment
      model was varied from 0.1 to 0.9 and tracer activity curves were calculated
      (60000 curves/parameter). A linear regression function was fitted to these
      curves. The comparison of the slope values of the regression function with the
      corresponding compartment data revealed a primary dependency on k3, which is
      associated with the intracellular phosphorylation of FDG. The squared correlation
      coefficient was high with r(2)=0.9716, which refers to 97 % explained variance of
      the data. k2 and vb had only a minor impact, while k1 and k4 had no impact on the
      slope values. The results demonstrate, that k3 has a major impact on the slope
      values calculated by the linear regression function.

PMID- 23145360
TI  - Radiolabelled probes for imaging of atherosclerotic plaques.
AB  - Cardiovascular disease is the leading cause of death worldwide. Unstable
      atherosclerotic plaques are prone to rupture followed by thrombus formation,
      vessel stenosis, and occlusion and frequently lead to acute myocardial infarction
      and brain infarction. As such, unstable plaques represent an important diagnostic
      target in clinical settings and the specific diagnosis of unstable plaques would
      enable preventive treatments for cardiovascular disease. To date, various imaging
      methods such as computed tomography (CT), magnetic resonance imaging (MRI),
      ultrasound (US), and intravascular ultrasound (IVUS) have been widely used
      clinically. Although these methods have advantages in terms of spatial resolution
      and the ability to make detailed identification of morphological alterations such
      as calcifications and vessel stenosis, these techniques require skill or
      expertise to discriminate plaque instability, which is essential for early
      diagnosis and treatment and can present difficulties for quantitative estimation.
      On the other hand, nuclear imaging techniques such as positron emission
      tomography (PET) and single photon emission computed tomography (SPECT) can
      noninvasively collect quantitative information on the expression levels of
      functional molecules and metabolic activities in vivo and thus provide functional
      diagnoses of unstable plaques with high sensitivity. Specifically, unstable
      plaques are characterized by an abundance of invasive inflammatory cells
      (macrophages), increased oxidative stress that increases oxidized LDL and its
      receptor expressed on cells in the lesions, increased occurrence of apoptosis of
      macrophages and other cells involved in disease progression, increased protease
      expression and activity, and finally thrombus formation triggered by plaque
      rupture, which is the most important mechanism leading to the onset of
      infarctions and ischemic sudden death. Therefore, these characteristics can all
      be targets for molecular imaging by PET and SPECT. In this paper, we review the
      present state and future of radiolabelled probes that have been developed for
      detecting atherosclerotic unstable plaques with nuclear imaging techniques.

PMID- 23145362
TI  - PET/MR in oncology: an introduction with focus on MR and future perspectives for
      hybrid imaging.
AB  - After more than 20 years of research, a fully integrated PET/MR scanner was
      launched in 2010 enabling simultaneous acquisition of PET and MR imaging.
      Currently, no clinical indication for combined PET/MR has been established,
      however the expectations are high. In this paper we will discuss some of the
      challenges inherent in this new technology, but focus on potential applications
      for simultaneous PET/MR in the field of oncology. Methods and tracers for use
      with the PET technology will be familiar to most readers of this journal; thus
      this paper aims to provide a short and basic introduction to a number of
      different MRI techniques, such as DWI-MR (diffusion weighted imaging MR), DCE-MR
      (dynamic contrast enhanced MR), MRS (MR spectroscopy) and MR for attenuation
      correction of PET. All MR techniques presented in this paper have shown promising
      results in the treatment of patients with solid tumors and could be applied
      together with PET increasing the amount of information about the tissues of
      interest. The potential clinical benefit of applying PET/MR in staging,
      radiotherapy planning and treatment evaluation in oncology, as well as the
      research perspectives for the use of PET/MR in the development of new tracers and
      drugs will be discussed.

PMID- 23145363
TI  - (18)F-DOPA PET with and without MRI fusion, a receiver operator characteristics
      comparison.
AB  - This study is a retrospective analysis of the diagnostic accuracy of FDOPA PET
      with MRI fusion to FDOPA PET without MRI fusion. Clinical FDOPA PET scans
      obtained between 2000 and 2008 at the University of Wisconsin Hospital and
      Clinics were assessed using measures derived from regions of interest (ROI)
      generated with fused MRI (fused group) and again with ROIs derived solely from
      PET data (non-fused groups). The ROIs were used to calculate ratios
      (Striatum/Occipital cortex, Striatum/Cerebellum) pertinent to Parkinson's disease
      (PD) pathology. The clinical records were assessed for demographic data, follow
      up length, and diagnosis. Receiver Operator Characteristics with area under the
      curve (AUC) measures were calculated and compared using confidence intervals and
      hypothesis testing. 27 patients had FDOPA PET with median clinical follow-up of 4
      years. Of these, 17 patients had FDOPA PET with a fusible MR image. Seven of the
      27 had a non-PD movement disorder. AUCs for the ratio measures ranged from 0.97
      1.0 (fused), 0.73-0.83 (non-fused), and 0.63-0.82 (matched non-fused). The fused
      images had improved accuracy compared to the matched non-fused and all non-fused
      groups for the striatum to occipital group (p=0.04, p=0.03), while the striatum
      to cerebellum ratio had improvement over the non-fused all group (p=0.041). MR
      fusion to FDOPA PET improves the accuracy of at least some measures
      (Striatum/Occiput, Striatum/Cerebellum) in the diagnosis of PD.

PMID- 23145364
TI  - Efficient multicistronic co-expression of hNIS and hTPO in prostate cancer cells
      for nonthyroidal tumor radioiodine therapy.
AB  - Radioiodine therapy has proven to be a safe and effective approach in the
      treatment of differentiated thyroid cancer. Similar treatment strategies have
      been exploited in nonthyroidal malignancies by transfecting hNIS gene into tumor
      cells or xenografts. However, rapid radioiodine efflux is often observed after
      radioiodine uptake, limiting the overall antitumor effects. In this study, we
      aimed at constructing multicistronic co-expression of hNIS and hTPO genes in
      tumor cells to enhance the radioiodine uptake and prolong the radioiodine
      retention. Driven by the cytomegalovirus promoter, hNIS and hTPO were
      simultaneously inserted into the expression cassette of adenoviral vector. An Ad5
      viral vector (Ad-CMV-hTPO-T2A-hNIS) was assembled as a gene therapy vehicle by
      Gateway technology and 2A method. The co-expression of hNIS and hTPO genes was
      confirmed by a double-label immunofluorescence assay. The radioiodine ((125)I)
      uptake and efflux effects induced by co-expression of hNIS and hTPO genes were
      determined in transfected and non-transfected PC-3 cells. Significantly higher
      uptake (6.58 +/- 0.56 fold, at 1 h post-incubation) and prolonged retention (5.47
      +/- 0.36 fold, at 1 h of cell efflux) of radioiodine ((125)I) were observed in
      hNIS and hTPO co-expressed PC-3 cells as compared to non-transfected PC-3 cells.
      We concluded that the new virus vector displayed favorable radioiodine uptake and
      retention properties in hNIS-hTPO transfected PC-3 cells. Our study will provide
      valuable information on improving the efficacy of hNIS-hTPO co-mediated
      radioiodine gene therapy.

PMID- 23145365
TI  - Synthesis and evaluation of (68)Ga-labeled DOTA-2-deoxy-D-glucosamine as a
      potential radiotracer in MUPET imaging.
AB  - The purposes of this study were to develop an efficient method of labeling D
      glucosamine hydrochloride with gallium 68 ((68)Ga) and investigate the imaging
      properties of the resulting radiotracer in a human tumor xenograft model using
      micro-positron emission tomography (MUPET). The precursor compound 1,4,7,10
      tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA)-2-deoxy-D-glucosamine
      (DOTA-DG) was synthesized from D-glucosamine hydrochloride and 2-(4
      isothiocyanatobenzyl)-DOTA. Radiolabeling of DOTA-DG with (68)Ga was achieved in
      10 minutes using microwave heating. The labeling efficiency a nd radiochemical
      purity after purification of (68)Ga-DOTA-DG were ~85% and greater than 98%,
      respectively. In A431 cells, the percentages of (68)Ga-DOTA-DG and (18)F-FDG
      uptakes after 60 min incubation were 15.7% and 16.2%, respectively. In vivo, the
      mean +/- standard deviation of (68)Ga-DOTADG uptake values in A431 tumors were
      2.38+/-0.30, 0.75+/-0.13, and 0.39+/-0.04 percent of the injected dose per gram
      of tissue at 10, 30, and 60 minutes after intravenous injection, respectively.
      MUPET imaging of A431-bearing mice clearly delineated tumors at 60 minutes after
      injection of (68)Ga-DOTA-DG at a dose of 3.7 MBq. (68)Ga-DOTA-DG displayed
      significantly higher tumor-to-heart, tumor-to-brain, and tumor-to-muscle ratios
      than (18)F-FDG did. Further studies are needed to identify the mechanism of tumor
      uptake of this new glucosamine-based PET imaging tracer.

PMID- 23145366
TI  - American Journal of Nuclear Medicine and Molecular Imaging: Editorial Board
      (2012) e-Century Publishing Corporation.

PMID- 23145367
TI  - Distinct roles for alpha-beta hydrolase domain 5 (ABHD5/CGI-58) and adipose
      triglyceride lipase (ATGL/PNPLA2) in lipid metabolism and signaling.
AB  - Catabolism of stored triacylglycerol (TAG) from cytoplasmic lipid droplets is
      critical for providing energy substrates, membrane building blocks, and signaling
      lipids in most cells of the body. However, the lipolytic machinery dictating TAG
      hydrolysis varies greatly among different cell types. Within the adipocyte, TAG
      hydrolysis is dynamically regulated by hormones to ensure appropriate metabolic
      adaptation to nutritional and physiologic cues. In other cell types such as
      hepatocytes, myocytes, and macrophages, mobilization of stored TAG is regulated
      quite differently. Within the last decade, mutations in two key genes involved in
      TAG hydrolysis, alpha-beta hydrolase domain 5 (ABHD5/CGI-58) and adipose
      triglyceride lipase (ATGL/PNPLA2), were found to cause two distinct neutral lipid
      storage diseases (NLSD) in humans. These genetic links, along with supporting
      evidence in mouse models, have prompted a number of studies surrounding the
      biochemical function(s) of these proteins. Although both CGI-58 and ATGL have
      been clearly implicated in TAG hydrolysis in multiple tissues and have even been
      shown to physically interact with each other, recent evidence suggests that they
      may also have distinct roles. The purpose of this review is to summarize the most
      recent insights into how CGI-58 and ATGL regulate lipid metabolism and signaling.

PMID- 23145368
TI  - The Role of EMT in Pancreatic Cancer Progression.

PMID- 23145370
TI  - [Usefulness of the Addenbrooke's Cognitive Examination (Spanish version) in
      Peruvian patients with Alzheimer's disease and Frontotemporal Dementia].
AB  - INTRODUCTION: The development of screening tools for the assessment of cognitive
      status in patients with dementia must be brief yet both highly sensitive and
      specific in order to ensure its clinical utility. In this sense, it is important
      to adapt tools widely used around the world to particular populations, allowing
      for a more proper validity of its use in everyday clinical practice. One of the
      most popular general cognitive screening tools is the Addenbrooke's Cognitive
      Examination (ACE), which has been adapted and validated in multiple languages and
      populations. OBJECTIVE: To assess the usefulness of the Peruvian version of the
      ACE in patients with dementia. MATERIALS AND METHODS: Healthy controls, patients
      with Alzheimer disease (AD) and patients with Frontotemporal Dementia (FTD) were
      assessed with the Peruvian version of the ACE, the ADAScog to determine dementia
      severity, and a complete neuropsychological battery. RESULTS: The Peruvian
      version of the ACE showed very good internal consistency, strong concurrent
      validity as revealed by significant correlations between the ACE total score and
      both the MMSE and ADAScog. The ACE was able to differentiate healthy controls
      from patients with dementia with high discriminatory accuracy. Using a cut-off
      score of 86 (out of 100), the ACE was exhibited a sensitivity of 100% and a
      specificity of 100%.

PMID- 23145371
TI  - [Epileptic mania].
AB  - Psychiatric manifestations in epilepsy allow us to explore the relationship
      between brain and behaviour, brain and the mind and brain and personality. This
      article reviews the available literature taking mania in the context of epilepsy
      to better understand the mechanisms that underlie this sindromatic expression and
      to serve as a starting point to improve our comprehension of our patients'
      clinical presentations. Additionally, mood as a cardinal symptom of mania is
      questioned as its epidemiology, clinical presentation, neurobiology and
      anatomoclinic findings are reviewed.

PMID- 23145369
TI  - P2Y receptors and kidney function.
AB  - Cellular release of nucleotides is of physiological importance to regulate and
      maintain cell function and integrity. Also in the tubular and collecting duct
      system of the kidney, nucleotides are released in response to changes in cell
      volume or luminal flow rate and act in a paracrine and autocrine way on
      basolateral and luminal P2Y receptors. Recent studies using gene knockout mice
      assigned a prominent role to G protein-coupled P2Y(2) receptors, which are
      activated by both ATP and UTP. The antidiuretic hormone, arginine-vasopressin
      (AVP), and possibly an increase in collecting duct cell volume induce ATP
      release. The subsequent activation of P2Y(2) receptors inhibits AVP-induced cAMP
      formation and water reabsorption, which stabilizes cell volume and facilitates
      water excretion. An increase in NaCl intake enhances luminal release of ATP and
      UTP in the aldosterone-sensitive distal nephron which by activating apical P2Y(2)
      receptors and phospholipase C lowers the open probability of the epithelial
      sodium channel ENaC, thereby facilitating sodium excretion. Thus, the renal
      ATP/UTP/P2Y(2) receptor system not only serves to preserve cell volume and
      integrity but is also regulated by stimuli that derive from body NaCl
      homeostasis. The system also inhibits ENaC activity during aldosterone escape,
      i.e. when sodium reabsorption via ENaC is inappropriately high. The P2Y(2)
      receptor tone inhibits the expression and activity of the Na-K-2Cl cotransporter
      NKCC2 in the thick ascending limb and mediates vasodilation. While the role of
      other P2Y receptors in the kidney is less clear, the ATP/UTP/P2Y(2) receptor
      system regulates NaCl and water homeostasis and blood pressure.

PMID- 23145372
TI  - [Evaluation of psychometric characteristics of the Argentinean version of the
      Hare Psychopathy Checklist: Youth Version].
AB  - In spite of the relevance on diagnosis, therapeutic strategies and prevention of
      psychopathy of the accurate assessment of psychopathic traits in youngsters, in
      Argentina the internationally widespread specific instruments have not been
      validated. This research is aimed to the assessment of the reliability and
      aspects of the validity of the Argentinean version of the Hare Psychopathy
      Checklist: Youth Version. Thus, thirty institutionalized juvenile offenders were
      simultaneously assessed by two raters who produced independent and a consensus
      scores. The raters used information from the same multiple sources of
      information. The results support that the Argentinian version of the scale is a
      reliable, homogeneous instrument with high internal consistence. The Intraclass
      Correlation Coefficient for the total score was .98 and the Cronbach's Alpha
      Coefficient was 0.96. Findings also support concurrent and convergent validity of
      the scale using correlation measures with other criteria and measures relevant to
      the construct, such as the score of non-violent offenses (r = 0.55; p= 0.002),
      the score of violent-offenses (r = 0.48; p = 0.008); Impulsivity scale score (r =
      0.44; p = 0.02) and the count of types of conduct problems (r = .65; p < 0,001).

PMID- 23145373
TI  - [Junguian therapeutic focus].
AB  - This article is intended to try give light to one of the questions that often
      reveals to the student of Psychology and Psychiatry on the application of Jungian
      psychotherapy. How is its praxis? Is it done face to face or does it use a couch?
      Which are the methods employed? On the basis of Jung's own claims that it defends
      no doctrine and only describes facts and leaves to everyone the freedom to deal
      with them, we will find from a fundamentally empirical analytic space. It does
      not work from a scheme systematized on the basis of a prior theoretical
      orthodoxy. On the contrary, each patient will be presented as a new challenge to
      the understanding of the therapist.

PMID- 23145374
TI  - [The importance of transference in Junguian psychotherapy].
AB  - Transference is an absolutely natural and spontaneous process which cannot be
      developed in an artificial and voluntary manner by the therapist. Transference is
      carried out in a subjective interpersonal relation consisting of a patient and an
      analyst. Jung will say he feels happy when transference takes place calmly or
      runs virtually unnoticed and the therapist can then focus on other therapeutic
      factors that play an important role. One could argue that Jungian psychotherapy
      consists of two people who get together to try to understand what is happening in
      the subconscious of one of them. The Jungian therapist is an active therapist who
      encourages and helps the patient to develop its individuation.

PMID- 23145375
TI  - [Depression. A symbolic archetypal psychopathology].
AB  - Jung understood that our psyche had an archetypal structure and that its best
      representant was mythology. This is a different theoretical framework, with an
      underlying anthropology that allows us to think pathology under other
      epistemologic concepts. Pathology can be thought as with positive and negative
      aspects to consider. This approach lets us consider different types of depression
      based on an archetypal mythologem, which allows us to think different forms of
      treatment.

PMID- 23145376
TI  - [Carl Gustav Jung, the myth of a man].
AB  - The aim of this article is to get closer to the myth of Jung, this is part of the
      inner experiences that took place in his first childhood, and in which we can
      already see the foundation of his work and the development of key concepts as:
      the unconscious, Self, archetype and individuation process. His life is the
      display of his unconscious and this is what his work is about. We cannot
      understand Jung without taking into account the fundamental importance that he
      gives to the inner world: the dreams and fantasies; and the direct contact that
      he has had with these aspects since he was a little boy.

PMID- 23145377
TI  - [Essay on the myth of oedipus].
AB  - Jung conceptualized the collective unconscious as the locus of the myths, the
      absolutely genuine and primary patterns of thinking and feeling of humanity. The
      legend of Oedipus or myth of incest is a irrefutable proof of its eternal
      validity. The present essay is an attempt to take an alternative look to a
      history that belong to all of us. Situations that are developed in this drama,
      like the characters involved in it may charge significance as an archetypal and
      essentially symbolic interpretation.

PMID- 23145378
TI  - [The spirit of art lives on the Essence of Poetry -from C. G. Jung to M.
      Heidegger].
AB  - Two major contemporary thinkers such as Carl Gustav Jung, Swiss physician who was
      born in 1875 and died in 1961 and Martin Heidegger, German philosopher born in
      1889 and died in 1976, venture in their extensive research on art and poetry on
      two aspects which are the subjects of the spirit and the human essence and that
      for years, while pursuing in our work, under the name of the transmission
      unconscious poetry. Then we shall point out in this article the articulations we
      find, first deploying the key points of the magnificent work of Jung on The
      phenomenon of spirit in art and science and that developed by Heidegger in his
      lecture on Holderlin and the Essence of Poetry.

PMID- 23145379
TI  - [Apropos the psychology of dementia praecox].

PMID- 23145380
TI  - [The psychology of dementia praecox (1907)].

PMID- 23145381
TI  - Efficacy of extended-release divalproex combined with "condensed" dialectical
      behavior therapy for individuals with borderline personality disorder.
AB  - BACKGROUND: Borderline personality disorder (BPD) is a significant psychiatric
      illness for which medication treatments are still being explored. The goal of
      this study was to assess divalproex extended release (ER) vs placebo for patients
      receiving dialectal behavior therapy (DBT). METHODS: Patients with BPD received 4
      weeks of "condensed DBT." Those with Symptom Checklist-90 (SCL-90) scores >150
      after this treatment were then randomly and blindly assigned to placebo or
      divalproex ER for 12 weeks. Repeated measures analysis of variance utilizing last
      observation carried forward was used to assess the results. RESULTS: Seventeen
      participants completed the full assessment. Two patients had a significant
      decrease in SCL-90 in the first 4 weeks, leaving 15 patients for the medication
      phase of the trial. There were no significant differences between the
      participants assigned to divalproex ER compared with placebo. However, there was
      a significant improvement in both groups from baseline to endpoint (P = .001).
      CONCLUSIONS: The response of 2 of 17 participants in the first 4 weeks prior to
      medication may point to a practice strategy in approaching outpatients with BPD.
      Although the patients had a decrease in symptoms during the study, there was no
      advantage observed for divalproex ER and DBT over placebo and DBT.

PMID- 23145382
TI  - Characteristics of children with juvenile bipolar disorder or disruptive behavior
      disorders and negative mood: can they be distinguished in the clinical setting?
AB  - BACKGROUND: Because of continuing controversy over distinguishing juvenile
      bipolar disorder (JBD) from disruptive behavior disorders (DBDs) in the clinical
      setting, we investigated whether referred children with a DBD and a negative mood
      component could be differentiated from those diagnosed with JBD. The distinction
      is important because treatments differ. METHODS: In this single-site sample, 96
      children with non-attention-deficit/hyperactivity DBD and depression were
      compared with 27 JBD children and 187 psychiatric comparison children on measures
      assessing behavior, functional impairment, symptom severity, psychopathology, and
      comorbid psychiatric diagnosis. RESULTS: Few differences were found between
      children with DBD and depression and those with JBD on measures of conduct
      problems, oppositionality, aggression, hostility, and psychopathology. More
      functional impairment was found in the JBD group who also had higher rates of
      comorbid posttraumatic stress disorder (PTSD), substance use disorders, and
      suicidality than the other groups. CONCLUSIONS: These results do not support the
      specificity of aggression as a defining criterion for JBD and clinicians
      assessing such patients also should consider complex DBDs with an associated
      depressive component in the differential diagnosis. Children with JBD must be
      specifically assessed for comorbid developmental trauma, substance abuse, and
      suicidality. The association between JBD and PTSD needs further investigation in
      clinical research.

PMID- 23145383
TI  - Determining the efficacy and tolerance of quetiapine extended release for the
      management of psychosis and accompanying acute behavioral disturbance in adult
      acute psychiatry.
AB  - BACKGROUND: This study was conducted to explore the efficacy and tolerability of
      quetiapine extended release (XR) to treat psychosis and accompanying acute
      behavioral disturbance in hospitalized psychiatric patients. METHODS: Patients
      with psychosis who displayed aggression were administered quetiapine XR (day 1
      mean dose: 293.3 mg). Symptoms and side effects were assessed prospectively over
      an 8-day period. Symptoms were measured by the Overt Aggression Scale and Brief
      Psychiatric Rating Scale (BPRS), and side effects were measured using the Simpson
      Angus Scale and Barnes Akathisia Rating Scale. RESULTS: Fifteen of 16 consenting
      patients completed the study. Aggression was significantly reduced by day 3.
      Psychopathology also was significantly reduced, with the greatest improvement in
      BPRS Thinking Disturbance subscale scores. No significant increase in movement
      side effects was seen by day 8. Seven participants were administered a
      concomitant sedating antipsychotic on an as-needed basis, particularly in the
      first 4 days of treatment; these participants displayed much greater aggression-
      but not psychopathology--at day 1, and it took longer for their aggression and
      psychopathology to improve compared with patients treated with quetiapine XR as
      the sole antipsychotic. CONCLUSIONS: Further research is needed before definitive
      recommendations can be made. However, current findings provide tentative support
      for quetiapine XR as a safe and effective medication for treating concurrent
      psychosis and behavioral disturbance, particularly in less severely aggressive
      patients.

PMID- 23145384
TI  - Prevalence of problem gambling in Iowa: revisiting Shaffer's adaptation
      hypothesis.
AB  - BACKGROUND: Pathological gambling (PG) is an important public health problem. We
      assessed the prevalence of PG and problem (at-risk) gambling in a random sample
      of Iowa adults and compared the results to survey data collected in 1989 and
      1995. The goal of this study was to examine whether continued expansion of
      gambling venues is associated with increased rates of problematic gambling
      behavior. METHODS: A random digit dialing telephone screening was conducted in
      eastern Iowa of men and women age >=18. Respondents were administered the South
      Oaks Gambling Screen (SOGS) to assess lifetime gambling behavior. Demographic and
      clinical variables were collected. RESULTS: A total of 356 respondents (147 men,
      209 women) completed the SOGS, and all reported lifetime gambling participation.
      PG (SOGS >=5) was found in 5 (1.4%) and problem gambling (SOGS = 3, 4) in 8
      (2.2%) respondents. Disordered gambling (SOGS >=3) was found in 13 (3.6%)
      respondents. Risk factors for disordered gambling included age (odds ratio [OR] =
      0.64 per 10-year age increase), income (OR = 0.82 per $10,000 increase), minority
      group status (OR = 5.75), number of lifetime gambling activities (OR = 1.27), and
      having ever gambled >=$100 (OR = 13.3). Overall gambling participation was
      significantly less in the current sample, compared with data collected in 1995.
      CONCLUSIONS: Recent gambling participation was less than in 1995, despite the
      continued expansion of gaming opportunities. Disordered gambling was associated
      with younger age, lower income, and minority group status. The results are
      consistent with Shaffer's "adaptation" hypothesis, which posits that following an
      initial increase in gambling participation, problematic gambling stabilizes at a
      lower level.

PMID- 23145385
TI  - Varenicline plus healthy lifestyle intervention for smoking cessation in
      psychotic disorders.
AB  - BACKGROUND: We were interested in exploring the efficacy and safety of
      varenicline as an adjunct to a healthy lifestyle intervention for smoking
      cessation among individuals with a severe mental illness. METHODS: We used
      varenicline as an adjunct to a healthy lifestyle intervention in 14 smokers with
      a psychotic illness. RESULTS: Overall, smoking cessation rates were 36% at 3
      months and 42% at 6 months. The most commonly reported side effects were sleep
      disturbance and nausea. These tended to occur early in treatment, and patients
      responded to general measures of support and reassurance. Of the 14 participants,
      1 dropped out because of psychiatric problems and 2 because of other side
      effects. CONCLUSIONS: Varenicline appears to be an effective adjunct to a healthy
      lifestyle intervention for smokers with a psychotic illness. Although the results
      of this open study are encouraging, replication in an adequately powered,
      randomized controlled trial is required before definitive conclusions can be
      drawn.

PMID- 23145386
TI  - Skin picking disorder is associated with other body-focused repetitive behaviors:
      findings from an internet study.
AB  - BACKGROUND: There is a lack of consensus on how to conceptualize skin picking
      disorder (SPD). It has been proposed that SPD is related to other problematic
      body-focused repetitive behaviors (BFRBs), such as hair pulling disorder (HPD)
      and problematic nail biting and cheek biting. METHODS: We compared rates of BFRBs
      in online samples of SPD sufferers and college students. We also examined family
      history of HPD and skin picking problems and correlates of BFRB comorbidity in
      the SPD sample. RESULTS: Prevalence of BFRBs was significantly higher in the SPD
      sample compared with the college student sample. One-half (50.8%) of the SPD
      sample had a first-degree relative with problematic skin picking, and 7.9% had a
      first-degree relative with diagnosed HPD. Finally, correlates of BFRB comorbidity
      indicated that when multiple habits co-occur in an individual, they tend to
      involve the same body area. CONCLUSIONS: These findings are the first to show
      that SPD and BFRBs other than HPD frequently co-occur. Furthermore, they extend
      previous work showing that SPD has a family component and suggest that SPD and
      HPD may run in the same families. Given the recruitment method and the self
      report nature of the comorbidity data, replication in clinical samples is needed.

PMID- 23145387
TI  - DSM-5 field survey: skin picking disorder.
AB  - BACKGROUND: Pathologic skin picking (skin picking disorder [SPD]) is a prevalent
      and disabling condition, which has received increasing study. It is timely to
      consider including SPD in DSM-5. The aim of this field survey was to investigate
      possible diagnostic criteria for SPD. METHODS: Patients age >10 with skin-picking
      symptoms were recruited. Patients were assessed with 2 modules based on the
      Structured Clinical Interview for DSM, which addressed proposed DSM-5 diagnostic
      criteria for SPD. Additional questions were included to test other possible
      diagnostic criteria. RESULTS: Thirty-eight patients had SPD. All had recurrent
      skin picking that resulted in skin lesions. Skin picking persisted despite
      repeated attempts to decrease or stop. "Urges" or "needs" to pull were not
      endorsed by all patients, but did correlate with severity of skin picking.
      "Resistance" to picking also was not universally endorsed. CONCLUSIONS: These
      data support the proposed DSM-5 diagnostic criteria for SPD. Although most
      patients have urges to pick or a sense of relief when picking, such phenomena are
      not universal and should not be included in the diagnostic criteria set. An
      additional criterion of repeated attempts to decrease or stop skin picking seems
      warranted.

PMID- 23145388
TI  - Smoking is associated with greater symptom load in bipolar disorder patients.
AB  - BACKGROUND: Individuals with mental illness have a higher prevalence of smoking
      than those without a mental illness. Nicotine has several effects on mood and
      cognition. After many studies, the nature of the effect of smoking on mental
      illness is not clear. METHODS: We performed a cross-sectional study of smoking
      status and symptom load in an outpatient bipolar disorder population. Data were
      collected and analyzed from 134 outpatients regarding smoking status and symptom
      profile and severity using the Rapid Psychiatric Interview Data scale. RESULTS:
      Smokers had more severe anxiety symptoms (5.2 +/- 7.6 vs 2.2 +/- 3.3, z = 3.8, P
      = .0001), depressive symptoms (9.0 +/- 9.6 vs 6.5 +/- 8.1, z = 3.2, P = .0015),
      and manic symptoms (3.0 +/- 4.2 vs 1.5 +/- 2.9, z = 2.1, P = .04) than
      nonsmokers. CONCLUSION: Smokers with bipolar disorder carry a greater symptom
      burden than nonsmokers. However, this is an associational study, and the true
      nature of the relationship is not clear.

PMID- 23145389
TI  - Overview of serotonin syndrome.
AB  - BACKGROUND: Serotonin syndrome (SS) is a rare and potentially life-threatening
      toxic state caused by an adverse drug reaction that leads to excessive central
      and peripheral serotonergic activity. This excessive serotonin hyperstimulation
      may be secondary to 1 standard therapeutic dose of a single agent, inadvertent
      interactions between various drugs, intentionally or unintentionally excessive
      use of particular drugs, deliberate self-harm, or recreational use of certain
      drugs. This review article serves as an overview of the epidemiology,
      pathophysiology, clinical features, diagnosis, differential diagnosis,
      management, and prevention of SS. METHODS: The authors conducted a MEDLINE search
      for the period covering 1955 to 2011. RESULTS: SS commonly occurs after the use
      of serotonergic agents alone or in combination with monoamine oxidase inhibitors.
      SS classically consists of a triad of signs and symptoms broadly characterized as
      alteration of mental status, abnormalities of neuromuscular tone, and autonomic
      hyperactivity. However, all 3 triads of SS may not occur simultaneously. Clinical
      manifestations are diverse and nonspecific, which may lead to misdiagnosis. SS
      can range in severity from mild to life-threatening. Most cases of SS are mild
      and resolve with prompt recognition and supportive care. Management of SS
      involves withdrawal of the offending agent(s), aggressive supportive care to
      treat hyperthermia and autonomic dysfunction, and occasionally the administration
      of serotonin antagonists--cyproheptadine or chlorpromazine. Patients with
      moderate and severe cases of SS require inpatient hospitalization. CONCLUSIONS:
      Psychiatrists, clinicians, and general practitioners must develop increased
      awareness of SS due to the current increase in the use of serotonergic agents in
      clinical practice. As SS is a manifestation of adverse pharmacology, it is not
      considered an idiosyncratic drug reaction, making it predictable and highly
      preventable. Most cases of SS are mild and easily managed. With prompt
      recognition and supportive care, more severe cases of SS have a favorable
      prognosis.

PMID- 23145390
TI  - No evidence for depression screening in cardiovascular care settings: a comment
      on CANMAT task force recommendations.

PMID- 23145391
TI  - Anticonvulsant treatment of compulsive sexual behavior.

PMID- 23145393
TI  - Orders for thyroid function tests - changes over 10 years.
AB  - In the BEACH (Bettering the Evaluation and Care of Health) program, between 2001
      02 and 2010-11, general practice orders for thyroid function tests increased by
      51%.

PMID- 23145394
TI  - Hypothyroidism.
AB  - BACKGROUND: Hypothyroidism is a common endocrine disorder that mainly affects
      women and the elderly. OBJECTIVE: This article outlines the aetiology, clinical
      features, investigation and management of hypothyroidism. DISCUSSION: In the
      Western world, hypothyroidism is most commonly caused by autoimmune chronic
      lymphocytic thyroiditis. The initial screening for suspected hypothyroidism is
      thyroid stimulating hormone (TSH). A thyroid peroxidase antibody assay is the
      only test required to confirm the diagnosis of autoimmune thyroiditis. Thyroid
      ultrasonography is only indicated if there is a concern regarding structural
      thyroid abnormalities. Thyroid radionucleotide scanning has no role in the work
      up for hypothyroidism. Treatment is with thyroxine replacement (1.6 MUg/kg lean
      body weight daily). Poor response to treatment may indicate poor compliance, drug
      interactions or impaired absorption. The significance of elevated TSH associated
      with thyroid hormones within normal range is controversial; thyroxine replacement
      may be beneficial in some cases. Unless contraindicated, iodine supplementation
      should be prescribed routinely in women planning a pregnancy. Where raised TSH
      levels are detected periconceptually or during pregnancy, specialist involvement
      should be sought.

PMID- 23145395
TI  - Evaluating and managing patients with thyrotoxicosis.
AB  - BACKGROUND: Thyrotoxicosis is common in the Australian community and is
      frequently encountered in general practice. Graves disease, toxic multinodular
      goitre, toxic adenoma and thyroiditis account for most presentations of
      thyrotoxicosis. OBJECTIVE: This article outlines the clinical presentation and
      evaluation of a patient with thyrotoxicosis. Management of Graves disease, the
      most frequent cause of thyrotoxicosis, is discussed in further detail.
      DISCUSSION: The classic clinical manifestations of thyrotoxicosis are often
      easily recognised by general practitioners. However, the presenting symptoms of
      thyrotoxicosis are varied, with atypical presentations common in the elderly.
      Following biochemical confirmation of thyrotoxicosis, a radionuclide thyroid scan
      is the most useful investigation in diagnosing the underlying cause. The
      selection of treatment differs according to the cause of thyrotoxicosis and the
      wishes of the individual patient. The preferred treatment for Graves disease is
      usually antithyroid drug therapy, almost always carbimazole. The primary
      treatment of a toxic multinodular goitre or toxic adenoma is usually radioactive
      iodine therapy. Specific therapy is usually not warranted in cases of
      thyroiditis, however, treatment directed at symptoms may be required. Referral to
      an endocrinologist is recommended if thyroiditis is unlikely or has been
      excluded.

PMID- 23145396
TI  - Goitre - causes, investigation and management.
AB  - BACKGROUND: Goitre refers to an enlarged thyroid. Common causes of goitre include
      autoimmune disease, thyroid nodules and iodine deficiency. OBJECTIVE: This
      article outlines the causes, investigation and management of goitre in the
      Australian general practice setting. DISCUSSION: Patients with goitre may be
      asymptomatic, or may present with compressive symptoms such as cough or
      dysphagia. Goitre may also present with symptoms due to associated hypothyroidism
      or hyperthyroidism. Thyroid stimulating hormone is the appropriate first test for
      all patients with goitre; if this hormone is low a radionuclide scan is helpful.
      Thyroid ultrasound has become an extension of physical examination and should be
      performed in all patients with goitre. Ultrasound can determine what nodules
      should be biopsied. Treatment options for goitre depend on the cause and the
      clinical picture and may include observation, iodine supplementation, thyroxine
      suppression, thionamide medication (carbimazole or propylthiouracil), radioactive
      iodine ablation and surgery.

PMID- 23145397
TI  - Thyroid disease in the perinatal period.
AB  - BACKGROUND: Thyroid hormone plays a critical role in fetal development. In
      pregnancy, increased thyroid hormone synthesis is required to meet fetal needs,
      resulting in increased iodine requirements. OBJECTIVE: This article outlines
      changes to thyroid physiology and iodine requirements in pregnancy, pregnancy
      specific reference ranges for thyroid function tests and detection and management
      of thyroid conditions in pregnancy. DISCUSSION: Thyroid dysfunction affects 2-3%
      of pregnant women. Pregnancy specific reference ranges are required to define
      thyroid conditions in pregnancy and to guide treatment. Overt maternal
      hypothyroidism is associated with adverse pregnancy outcomes; thyroxine treatment
      should be commenced immediately in this condition. Thyroxine treatment has also
      been shown to be effective for pregnant women with subclinical hypothyroidism who
      are thyroid peroxidase antibody positive. Gestational thyrotoxicosis needs to be
      differentiated from Graves disease and rarely requires thionamide treatment.
      Postpartum thyroiditis most commonly presents with isolated hypothyroidism but a
      biphasic presentation and isolated hyperthyroidism can occur: a high index of
      suspicion is warranted for diagnosis.

PMID- 23145398
TI  - Thyroid scans.
AB  - This article forms part of our 'Tests and results' series for 2012, which aims to
      provide information about common tests that general practitioners order
      regularly. It considers areas such as indications, what to tell the patient, what
      the test can and cannot tell you and interpretation of results.

PMID- 23145399
TI  - Thyroid therapy - tips and traps.
AB  - CASE STUDY: Thea, aged 63 years, presents for review after a small inferior
      myocardial infarction (MI) 3 months previously.

PMID- 23145400
TI  - The recovery paradigm - a model of hope and change for alcohol and drug
      addiction.
AB  - BACKGROUND: Alcohol and drug disorders remain major health and social problems in
      Australia, contributing enormously to the global burden of disease and the
      everyday practice of primary care. A recent growth in recovery research and
      recovery focused policies are starting to have an impact in Australia, with
      implications for how we attempt to resolve these problems. OBJECTIVE: In this
      article we discuss recent international findings in recovery research, and
      explore their implications for primary care. DISCUSSION: Research indicates that
      over half of dependent substance users will eventually achieve stable recovery.
      Key predictors of recovery are active engagement in the community and immersion
      in peer support groups and activities. Recovery requires a twin track approach:
      enabling and supporting individual recovery journeys, while creating
      environmental conditions that enable and support a 'social contagion' of
      recovery, in which recovery is transmitted through supportive social networks and
      dedicated recovery groups, such as mutual aid.

PMID- 23145401
TI  - Gastric distension.
AB  - CASE STUDY: A woman, 82 years of age, presented to the emergency department with
      an 8 day history of worsening generalised abdominal pain, nonfaecal emesis and
      abdominal distension associated with a background history of 20 kg weight loss
      over the past few months.

PMID- 23145402
TI  - Retroauricular cutaneous advancement flap.
AB  - BACKGROUND: Excisional surgery of the ear, such as that following a skin cancer
      excision, often produces a smaller ear postoperatively. OBJECTIVE: This article
      describes the various uses of a retroauricular cutaneous advancement flap to
      repair surgical defects of the ear following a skin cancer excision, without
      miniaturising the ear. DISCUSSION: A retroauricular cutaneous advancement flap is
      an option for patients who require cosmetically satisfying reconstruction of the
      ear post skin cancer excision. The technique can avoid the miniaturisation of the
      ear that may occur with other techniques.

PMID- 23145403
TI  - Progressive rash - a case study.
AB  - CASE STUDY: A man, 69 years of age, who previously had worked in the petroleum
      industry, presented with a 20 year history of an episodic rash on his arms, legs
      and trunk.

PMID- 23145404
TI  - Case conferences in palliative care - a substudy of a cluster randomised
      controlled trial.
AB  - BACKGROUND: In palliative care, case conferences have demonstrated improved
      maintenance of function and a significant reduction in hospitalisations. This
      study aimed to define the content and themes of palliative care case conferences.
      METHODS: This was a substudy of a cluster randomised controlled trial. Case
      conferences meeting the requirements for Medicare Benefits Schedule reimbursement
      were organised by the research officer in conjunction with the general
      practitioner and the participating palliative care service. All were audiotaped,
      coded and analysed for content and themes, using qualitative methods and
      interaction analysis. RESULTS: Seventeen case conferences were transcribed and
      coded. Physical issues were the dominant topic. Management of psychosocial
      concerns were rarely discussed. Lack of information was a common theme and time
      was spent during each conference ensuring all people were familiar with the
      issues and patient history. Healthcare professionals tended to respond to the
      content of patient concerns, but not the emotion. DISCUSSION: The discussions
      were complex and health professional participants rarely summarised information
      or checked that patients and carers had understood the information provided.

PMID- 23145405
TI  - When death is imminent - documenting end-of-life decisions.
AB  - BACKGROUND: There has been widespread promotion of advance care planning in
      recent years, which is consistent with an ageing population and a greater
      awareness of patient self determination. METHODS: A review of medical records
      relating to hospital patient deaths and a separate review of emergency department
      admissions of patients aged 75 years or more in the same hospital. RESULTS: In
      the patient deaths sample, 77% of patients (median age 79 years), had their first
      documented end-of-life discussion 3 days before death. In the sample of emergency
      department admissions, 82% of patients (median age 83 years), had no documented
      end-of-life discussion or review by the time of discharge. Only two patients,
      both in the emergency department admissions group, had written advance care plans
      before admission. DISCUSSION: This study suggests that documented advance care
      plans are either not being prepared in the community or are not being
      communicated to acute care facilities. As a result, end-of-life care preferences
      are documented when death is imminent.

PMID- 23145406
TI  - Potential roles for practice nurses in preventive care for young people - a
      qualitative study.
AB  - BACKGROUND: Increasing numbers of practice nurses and their expanding roles in
      Australian general practice suggest they can contribute to quality primary
      healthcare for young people. METHODS: Seventeen health and community
      professionals and a purposefully selected group of 12 practice nurses were
      interviewed about the role of the practice nurse in young people's healthcare. A
      directed content approach to analysis was applied. RESULTS: Participants
      recognised the psychosocial health burdens young people experience and the
      barriers they perceive in accessing healthcare. With good communication skills
      and appropriate training, practice nurses were perceived to be able to have an
      important role in the preventive care of young people. DISCUSSION: Practice
      nurses can contribute to breaking down barriers to healthcare for young people.
      This study is being reported on at an opportune time, considering the
      implications for young people of the 'Practice Nurse Incentive Program'.

PMID- 23145407
TI  - A is for aphorism - if 'a physician who treats himself has a fool for a patient' 
      are we all fools?
AB  - Sir William Osler was a great physician and medical educator and many of his wise
      teachings have survived the passage of time, including the counsel about self
      treatment - the title of this article.

PMID- 23145408
TI  - Cape York Paediatric Outreach Clinic - improving access to primary care in the
      Cape York peninsula region.
AB  - This article forms part of our 'Access' series for 2012, profiling organisations
      that provide primary healthcare to groups who are disadvantaged or have
      difficulty accessing mainstream services. The aim of this series is to describe
      the area of need, highlight the innovative strategies that have been developed by
      specific organisations to address this need, and make recommendations to help GPs
      improve access to disadvantaged populations in their own communities.

PMID- 23145409
TI  - Avoiding 'consultation interruptus' - a model for the daily supervision and
      teaching of general practice registrars.
AB  - BACKGROUND: In general practice placements, much of the teaching occurs when the
      supervisor is called into the consulting room by the registrar while the patient
      is still present. How should this unique learning environment affect on teaching
      strategies? OBJECTIVE: This article analyses the nature of general practice
      teaching and proposes a different model of teaching in a 'patient-present'
      environment. DISCUSSION: General practice registrars are advanced learners who
      benefit from exploration of clinical reasoning in patient encounters. However,
      teaching interactions that undermine the patient-registrar relationship will
      affect the registrar's exposure to continuity of care. In this article, a model
      for the supervisor to follow when entering the registrar's consulting room while
      the patient is still present is described. This model emphasises leaving the
      registrar in control of the consultation and the use of 'thinking aloud' to
      explore clinical reasoning while at the same time preserving the relationship
      between registrar and patient.

PMID- 23145410
TI  - Urban community based medical education - general practice at the core of a new
      approach to teaching medical students.
AB  - BACKGROUND: The benefits of community based medical education for both students
      and teachers are becoming increasingly clear. Rural programs offering year-long
      general practice based clinical training for medical students are well
      established and highly successful. Urban general practice teaching is currently
      more likely to be based on short term placements. OBJECTIVE: To describe a new
      model for urban community based medical education - the Onkaparinga Clinical
      Education Program - and to discuss its impact on general practitioners, community
      based specialists and other stakeholders. DISCUSSION: New approaches have been
      used to successfully translate rural community based medical education models to
      the urban setting. There is significant potential for urban community based
      medical education to be extended if adequate support and funding is available.
      Programs that allow students to access the rich patient care environment of
      community practice in urban areas can be rewarding for all involved.

PMID- 23145411
TI  - Addressing antibiotic resistance - focusing on acute respiratory infections in
      primary care.
AB  - We have been aware for decades - perhaps as a somewhat far-off theoretical
      problem - that antibiotic resistance is a threat to healthcare worldwide.
      However, the crisis is now here and very real. Each year in Europe alone, 25 000
      deaths are directly attributed to antibiotic resistance. New antibiotics are not
      being produced fast enough, and resistance means we are running out of
      antibiotics of last resort.

PMID- 23145412
TI  - Management of COPD in general practice.
AB  - Chronic obstructive pulmonary disease (COPD) management was investigated in two
      sub-studies of the BEACH (Bettering the Evaluation and Care of Health) program at
      5711 general practitioner-patient encounters in February to March 2010 and April
      to May 2011.

PMID- 23145413
TI  - Bronchiectasis - a guide for primary care.
AB  - BACKGROUND: While bronchiectasis not related to cystic fibrosis remains a
      significant cause of chronic respiratory disease in low to middle income
      countries, it has a lower profile in Australia. Nonetheless, there is increasing
      recognition that people living in Australia can present for the first time with
      noncystic fibrosis bronchiectasis at all stages of life. In addition, clinicians
      are often faced with the conundrum of minor changes consistent with
      bronchiectasis incidentally reported on computed tomography scan. OBJECTIVE: This
      article aims to provide advice regarding when to suspect bronchiectasis, how to
      proceed with confirming or refuting a diagnosis, and the principles of management
      to minimise disease progression and manage the acute exacerbations, symptoms and
      associated disability and impaired quality of life. DISCUSSION: Delay in the
      diagnosis, investigation and management of bronchiectasis in both children and
      adults is common, and this delay has been shown to be associated with more rapid
      progression of disease. General practitioners have a key role in suspecting and
      accurately diagnosing and assessing bronchiectasis, discussing potential cases
      with specialist respiratory colleagues early and leading a multidisciplinary team
      to help patients with bronchiectasis manage their disease and minimise disability
      and premature death.

PMID- 23145414
TI  - 'Is it okay for me to ... ?' Assessment of recreational activity risk in patients
      with chronic lung conditions.
AB  - BACKGROUND: Recreational activities, including travel, can be associated with
      risks to health. Assessing and advising on these risks can be an important part
      of travel planning for a person with a chronic lung condition when they ask, 'Is
      it okay for me to ...?' OBJECTIVE: This article discusses the respiratory
      considerations important in the assessment of, and advice for, a proposed
      activity in a person with a chronic lung condition. DISCUSSION: Patients with
      chronic lung disease can safely engage in a range of recreational, sporting and
      other activities. However, there are a number of general factors that should be
      taken into account, including access to, and the standard of, medical care
      available and the travel destination and medication availability. Guidelines
      based on limited evidence and expert opinion are available for some activities,
      but not all. Simple precautions and a common sense approach guided by knowledge
      of the particular risks in each setting should ensure a satisfactory outcome for
      the patient who asks, 'Is it okay for me to ... ?'

PMID- 23145415
TI  - Respiratory problems - occupational and environmental exposures.
AB  - BACKGROUND: The respiratory tract comes into contact with approximately 14 000
      litres of air during a standard working week. The quality of the air we breathe
      has major implications for our respiratory health. Any part of the respiratory
      tract, from the nose to the alveoli, may be adversely affected by exposure to
      airborne contaminants. OBJECTIVE: This article outlines some common occupational
      and environmental exposures that can lead to respiratory problems. DISCUSSION:
      Some of the effects of exposures may be immediate, whereas others such as
      asbestos-related lung disease may not present for many decades. Airborne
      contaminants may be the primary cause of respiratory disease or can exacerbate
      pre-existing respiratory conditions such as asthma and chronic obstructive
      pulmonary disease. Clinicians should have a high index of suspicion and question
      their patients with breathing problems about occupational and environmental
      exposures, especially in the setting of new onset symptoms.

PMID- 23145416
TI  - Towards an endgame for tobacco.
AB  - BACKGROUND: The reduction in smoking in Australia in the past 30 years has
      established the conditions in which elimination of smoking should now be
      considered. This is sometimes referred to as the 'tobacco endgame'. A range of
      approaches can be considered and any that are implemented would build on current
      actions such as plain packaging. OBJECTIVE: This article outlines possible public
      health and policy approaches with the goal of leading to the elimination of
      smoking, and discusses a potential target date for the elimination of smoking in
      Australia. DISCUSSION: The most effective strategy for eliminating smoking in
      Australia is likely to be one that reverses the tolerable, addictive nature of
      modern tobacco by the elimination of all additives and by specifying a very low
      level of true nicotine delivery. Use of an unsatisfying, costly and toxic product
      would naturally, and rapidly, decline.

PMID- 23145417
TI  - MRI of the knee.
AB  - Magnetic resonance imaging (MRI) is the gold standard in noninvasive
      investigation of knee pain. It has a very high negative predictive value and may
      assist in avoiding unnecessary knee arthroscopy; its accuracy in the diagnosis of
      meniscal and anterior cruciate ligament (ACL) tears is greater than 89%; it has a
      greater than 90% sensitivity for the detection of medial meniscal tears; and it
      is probably better at assessing the posterior horn than arthroscopy.

PMID- 23145418
TI  - Newly diagnosed early breast cancer - an update on pre-operative assessment and
      staging.
AB  - BACKGROUND: Most breast cancer seen in developed nations is diagnosed at an early
      stage and surgery is the recommended first line treatment in most cases.
      OBJECTIVE: This article reviews the current approach and related evidence on pre
      operative assessment of women with newly diagnosed breast cancer. It discusses
      the use of conventional assessment tools (mammography, ultrasound and needle
      biopsy) for staging the breast and axilla, the evidence relating to breast
      magnetic resonance imaging and the indications for staging investigations for
      distant metastatic disease. It highlights recent changes in practice, including
      areas of nonconsensus, and informs general practitioners on evolving issues in
      the pre-operative care of the newly diagnosed breast cancer patient. DISCUSSION:
      Once a breast cancer diagnosis has been established, appropriate pre-operative
      evaluation to assess the extent of disease (locally and sometimes systemically)
      helps guide surgical management and decisions on adjuvant therapy.

PMID- 23145419
TI  - Laparoscopic adjustable gastric banding - under-diagnosed late respiratory
      complications.
AB  - With the current epidemic of obesity in Australia, bariatric surgery has become
      increasingly accessible for patients with a body mass index above 35 kg/mA2.
      Laparoscopic adjustable gastric banding (LAGB) is currently the weight loss
      surgery of choice for its perceived simplicity and its low peri-operative
      complication and mortality rates. The short term complications and long term
      benefits of sustained weight loss with LAGB are well described but the medium
      term respiratory complications are less clearly appreciated. We report three
      cases with LAGB who presented with significant respiratory tract symptoms to the
      Nepean Hospital in New South Wales, a teaching hospital with a busy LAGB service,
      during the period from January to March 2012.

PMID- 23145420
TI  - Overactive bladder syndrome - management and treatment options.
AB  - BACKGROUND: Overactive bladder syndrome is a symptom-based clinical diagnosis. It
      is characterised by urinary urgency, frequency and nocturia, with or without urge
      urinary incontinence. These symptoms can often be managed in the primary care
      setting. OBJECTIVE: This article provides a review on overactive bladder syndrome
      and provides advice on management for the general practitioner. DISCUSSION:
      Overactive bladder syndrome can have a significant effect on quality of life, and
      affects 12-17% of the population. Prevalence increases with age. The management
      of overactive bladder syndrome involves exclusion of underlying pathology. First
      line treatment includes lifestyle interventions, pelvic floor exercises, bladder
      training and antimuscarinic agents. Failure of conservative management
      necessitates urology referral. Second line therapies are more invasive, and
      include botulinum toxin, neuromodulation or surgical interventions such as
      augmentation cystoplasty or urinary diversion.

PMID- 23145421
TI  - Multiple finger nodules and an erythematous rash - a case study.
AB  - CASE STUDY: A previously well male, 18 years ofA age, from a rural community,
      presentedA with three painful, itchy nodules onA the fingers of his left hand,
      which hadA been present for 1 week. He had beenA prescribed amoxicillin
      clavulanate butA presented again when there was noA improvement after 4 days of
      takingA antibiotics. Examination revealed threeA erythematous and umbilicated
      nodulesA without any halo, but with a centralA depression with exudate (Figure
      1a). NoA specific treatment was instituted at thisA visit. One week later the
      patient re-presentedA with new erythematous lesions on the palms and dorsum of
      his hands. The original three lesions had improved andA were drier than
      previously (Figure 1b,A c). The new lesions disappeared afterA 2 weeks and the
      original lesions after 4A weeks, without any other treatment.

PMID- 23145422
TI  - Making sense of MRI of the lumbar spine.
AB  - BACKGROUND: With improved accessibility and increasing use of magnetic resonance
      imaging (MRI) to evaluate low back pain, general practitioners are exposed to a
      set of recommended terminology used among the various specialties involved in
      lumbar spinal conditions. OBJECTIVE: This article aims to illustrate these
      descriptive terms, the various lumbar spinal pathology and its clinical
      implications regarding management. DISCUSSION: MRI may be useful in specific
      clinical situations in lumbar back pain, however, the importance of a thorough
      clinical assessment cannot be overstated. An understanding of the benefits and
      limitations of MRI in evaluating lumbar back pain and improved communiction
      between healthcare providers, should allow for optimal management of the
      patient's radiologically matched clinical issues.

PMID- 23145423
TI  - Rash in the returned traveller.
AB  - CASE STUDY: An otherwise healthy male patient, 45 years of age, presented to a
      general practice clinic in regional Western Australia 1 week after developing a
      pruritic, spreading rash that started after returning from a holiday in Thailand
      with his family. He denied infective symptoms such as fever, rigors or chills. He
      had not been bitten by either mosquitoes or marine life during his stay.
      Examination revealed rash in several distinct areas over the left flank (Figure
      1). The rash was erythematous and serpiginous (Figure 2). Some excoriations were
      present. He was afebrile and did not have any palpable lymphadenopathy. The
      general practitioner was in doubt as to the diagnosis and sought assistance
      through Tele-Derm National, a service provided by the Australian College of Rural
      and Remote Medicine (ACCRM). The GP submitted brief case notes and several
      photographs of the rash via the online portal. Within the hour, a diagnostic and
      management plan was prepared by a dermatologist and an SMS notification of the
      findings sent to the referring GP.

PMID- 23145424
TI  - Managing chronic hepatitis B - the role of the GP.
AB  - BACKGROUND: General practitioners are critical to reducing the impact of chronic
      hepatitis B in the community. This study explored how GPs understand their role
      in chronic hepatitis B management. METHODS: Semi-structured interviews were held
      with 26 GPs from five Australian jurisdictions. RESULTS: The principal roles
      identified by GPs in chronic hepatitis B management were diagnosis, monitoring
      and mediating between patient and specialist. General practitioners saw
      themselves as essential in managing chronic hepatitis B with their frequent
      interaction with patients, physical access and established trusting therapeutic
      relationships. They supported an active role in the delivery of chronic hepatitis
      B pharmaceutical treatment through shared care arrangements. DISCUSSION: An
      optimal public health response to chronic hepatitis B requires a clear definition
      of the role of the GP. Most GPs believed their role could be more substantive and
      include management and treatment beyond that of diagnosis and monitoring.

PMID- 23145425
TI  - Patients with colorectal cancer - a qualitative study of referral pathways and
      continuing care.
AB  - BACKGROUND: This article explores the views of general practitioners on their
      referral of colorectal cancer patients following diagnosis to specialist
      surgeons. METHODS: Sampling was purposive. Nineteen GPs representing urban and
      rural areas participated in four focus groups. RESULTS: General practitioners
      viewed their relationship with surgeons to be of prime importance in the decision
      about whom to refer. This relationship allowed faster referrals and improved
      feedback from the specialist to the GP. General practitioners preferred referral
      to the private health services because they perceived delays in the public system
      and that referral and communication was easier with private specialists. Neither
      the volume of colorectal cancer work nor the availability of a multidisciplinary
      team influenced their decision making. DISCUSSION: The relationship and
      communication between GP and surgeon are important in facilitating the referral
      pathway and the continuing role that many GPs would like to have in the care of
      their patients.

PMID- 23145426
TI  - Women survivors of child abuse - don't ask, don't tell.
AB  - BACKGROUND: Rates of disclosure of child abuse by women survivors are low, and
      general practitioners seldom ask women about such history. This study explored
      the experiences of women survivors: child abuse disclosure, GP service use and
      thoughts on being asked about their abuse experiences. METHODS: A cross-sectional
      study containing quantitative and qualitative questions was conducted with 108
      women child abuse survivors. RESULTS: Only 5% of the women disclosed their child
      abuse to their GP and 19% were asked about their child abuse history. More than
      half of the women (58%) asked reported feeling hopeful or relieved and none
      reported feeling offended. DISCUSSION: Rates of child abuse inquiry by GPs and
      disclosures by women survivors remain low. With the majority of women survivors
      reporting feeling relieved and none offended when asked about their child abuse
      experiences, GPs should consider asking women who present to their practice about
      such experiences: This may facilitate early intervention.

PMID- 23145427
TI  - Wudinna Health Centre - improving access to primary care in a remote community.
AB  - Workforce issues present a major barrier to equitable access to health services
      for patients living in regional and remote areas. This article describes the
      development of a health centre to consolidate the major primary healthcare
      providers of a very remote community. The new health centre has resulted in
      measurable improvements in access to primary healthcare services in the region.

PMID- 23145428
TI  - A is for aphorism - the power of silence.
AB  - 'All you have to do is listen' is the title of Rob Kapilow's delightful book on
      classical music; but he could equally have been talking about general practice
      consultations. Listening requires several skills including attention, echoing and
      body language, but begins with silence. Well timed silences, used judiciously,
      can allow the patient adequate space to express symptoms and concerns, while
      allowing the general practitioner more time for attention, comprehension and
      synthesis.

PMID- 23145429
TI  - A laboratory system for element specific hyperspectral X-ray imaging.
AB  - X-ray tomography is a ubiquitous tool used, for example, in medical diagnosis,
      explosives detection or to check structural integrity of complex engineered
      components. Conventional tomographic images are formed by measuring many
      transmitted X-rays and later mathematically reconstructing the object, however
      the structural and chemical information carried by scattered X-rays of different
      wavelengths is not utilised in any way. We show how a very simple; laboratory
      based; high energy X-ray system can capture these scattered X-rays to deliver 3D
      images with structural or chemical information in each voxel. This type of
      imaging can be used to separate and identify chemical species in bulk objects
      with no special sample preparation. We demonstrate the capability of
      hyperspectral imaging by examining an electronic device where we can clearly
      distinguish the atomic composition of the circuit board components in both
      fluorescence and transmission geometries. We are not only able to obtain
      attenuation contrast but also to image chemical variations in the object,
      potentially opening up a very wide range of applications from security to medical
      diagnostics.

PMID- 23145430
TI  - Double nucleophilic attack on isocyanide carbon: a synthetic strategy for 7-aza
      tetrahydroindoles.
AB  - A novel and efficient route for the synthesis of 7-aza-tetrahydroindoles from N
      aryl/alkyl-alkenoylacetamides and ethyl isocyanoacetate is described. A
      mechanism, involving a stepwise [3+2] cycloaddition-intramolecular aza-Michael
      addition cascade, is proposed that explains the origin of the double nucleophilic
      attack on the isocyanide carbon atom.

PMID- 23145432
TI  - Janus nanoparticle magic: selective asymmetric modification of Au-Ni
      nanoparticles for its controllable assembly onto attapulgite nanorods.
AB  - Janus Au-Ni particles are modified asymmetrically with polymer brushes. The
      asymmetric chemistry affect their binding onto catecholic attapulgite nanorods
      either through the Au domains or through the Ni domains.

PMID- 23145431
TI  - gamma-Selective directed catalytic asymmetric hydroboration of 1,1-disubstituted
      alkenes.
AB  - Directed catalytic asymmetric hydroborations of 1,1-disubstituted alkenes afford
      gamma-dioxaborato amides and esters in high enantiomeric purity (90-95% ee).

PMID- 23145433
TI  - Simple and sensitive fluorescence detection of the RNA endonuclease activity of
      mammalian argonaute2 protein based on an RNA molecular beacon.
AB  - A new strategy for determining the RNA endonuclease activity of mammalian
      argonaute2 (Ago2) protein has been developed, which combines the unique cleavage
      function of Ago2 protein with an RNA molecular beacon (RMB). Through the
      fluorescence restoration of the RMB, simple and sensitive detection of Ago2 is
      achieved.

PMID- 23145434
TI  - Palladium-catalyzed highly efficient synthesis of tetracenes and pentacenes.
AB  - Pd(0)-catalyzed cascade reactions of 1,7-diyn-3,6-bis(propargyl carbonate) with
      organoboronic acids have been developed, which provide one-pot access to
      functionalized tetracenes or pentacenes.

PMID- 23145436
TI  - Assembly of an unbalanced charged polyampholyte onto Nafion(r) to produce high
      performance composite membranes.
AB  - A novel SPES-NH(2)-GA-Nafion(r) composite membrane with higher proton
      conductivity and lower methanol permeability was fabricated by covalent
      crosslinking layer-by-layer self-assembly of an unbalanced charged polyampholyte
      (SPES-NH(2)) and glutaraldehyde (GA) with controllable free sulfonic acid
      content.

PMID- 23145435
TI  - Electrochemical direct detection of DNA deamination catalyzed by APOBEC3G.
AB  - APOBEC3G catalyzes deamination of cytosines in HIV-1 genome, and restricts the
      HIV-1 infection. Here, we propose a picomole-scale assay for the detection of DNA
      deamination catalyzed by APOBEC3G. Our results show the suitability of the
      developed method for a time course analysis of enzyme-catalyzed DNA
      modifications.

PMID- 23145438
TI  - The relationship of mammographic density and age.

PMID- 23145437
TI  - Long genomic DNA amplicons adsorption onto unmodified gold nanoparticles for
      colorimetric detection of Bacillus anthracis.
AB  - Unmodified gold nanoparticles (GNPs) can be wrapped with long genomic single- and
      double-stranded DNA (ssDNA and dsDNA) molecules produced by asymmetric polymerase
      chain reaction (As-PCR). More importantly, the DNA-Au interaction can be utilized
      for colorimetric detection of a specific nucleic acid sequence in clinical
      samples.

PMID- 23145439
TI  - Hematocolpos resulting from an imperforated hymen diagnosed by ultrasound in a
      patient with recurrent urinary tract infections.

PMID- 23145440
TI  - Henoch Schonlein purpura: a cause of abdominal pain in a 12-year-old female.

PMID- 23145441
TI  - Progesterone to treat vasomotor symptoms.

PMID- 23145442
TI  - Testosterone concentrations in ovarian insufficiency: a review.

PMID- 23145443
TI  - Profile: Montreal Cardiology Institute, Canada.

PMID- 23145444
TI  - UPDATE programmes of the European Society of Cardiology.

PMID- 23145445
TI  - Long-term effects of the Women's Health Initiative in the United States.

PMID- 23145446
TI  - Cigarette smoking and age of menopause.

PMID- 23145447
TI  - Postmenopausal endometriosis--a new dimension.

PMID- 23145448
TI  - Memory symptoms during the menopausal transition.

PMID- 23145449
TI  - Exercise, diet, weight loss and glucose metabolism.

PMID- 23145450
TI  - New drug development for cognitive enhancement in mental health: challenges and
      opportunities.

PMID- 23145451
TI  - Pharmacological cognitive enhancement in healthy people: potential and concerns.

PMID- 23145452
TI  - Special issue on advances in bioinformatics, biomedicine, and health informatics.

PMID- 23145453
TI  - Presidential address. Transposable elements, epigenetics, and genome evolution.

PMID- 23145454
TI  - "To predict or not to predict -- that is the question". An exploration of risk
      assessment in the context of South African forensic psychiatry.

PMID- 23145455
TI  - Power struggle: the Supreme Court's recent term focused on whether the
      Constitution limits federal authority and power.

PMID- 23145456
TI  - Agoraphobia -- the risk of untreated panic disorder. Panic Awareness Day, 10 July
      2012.

PMID- 23145457
TI  - Patients as Partners. Diabetes: what's depression got to do with it?

PMID- 23145458
TI  - Patients as Partners. 11% of non-natural deaths in SA due to suicide. Suicide
      Prevention Day, 10 September 2011.

PMID- 23145459
TI  - Patients as Partners. Sleep your way to better mental health.

PMID- 23145460
TI  - Acute pain management in the postanesthesia care unit.
AB  - Pain management in the postanesthesia care unit (PACU) is continually evolving,
      with several new nonopioids expanding the list of available agents. Pain in the
      PACU is not an inevitable outcome of surgery. With careful planning, multimodal
      analgesic techniques instituted preoperatively will reduce pain in the PACU.
      Accurate assessment of the characteristics of pain will direct rational drug
      choices while minimizing side effects. Better management of pain in the PACU
      setting will likely improve patient satisfaction and facilitate shorter PACU
      stays.

PMID- 23145461
TI  - Dissection of hydrogen bond interaction network around an iron-sulfur cluster by
      site-specific isotope labeling of hyperthermophilic archaeal Rieske-type
      ferredoxin.
AB  - The electronic structure and geometry of redox-active metal cofactors in proteins
      are tuned by the pattern of hydrogen bonding with the backbone peptide matrix. In
      this study we developed a method for selective amino acid labeling of a
      hyperthermophilic archaeal metalloprotein with engineered Escherichia coli
      auxotroph strains, and we applied this to resolve the hydrogen bond interactions
      with the reduced Rieske-type [2Fe-2S] cluster by two-dimensional pulsed electron
      spin resonance technique. Because deep electron spin-echo envelope modulation of
      two histidine (14)N(delta) ligands of the cluster decreased non-coordinating
      (15)N signal intensities via the cross-suppression effect, an inverse labeling
      strategy was employed in which (14)N amino acid-labeled archaeal Rieske-type
      ferredoxin samples were examined in an (15)N-protein background. This has
      directly identified Lys45 N(alpha) as providing the major pathway for the
      transfer of unpaired electron spin density from the reduced cluster by a "through
      bond" mechanism. All other backbone peptide nitrogens interact more weakly with
      the reduced cluster. The extension of this approach will allow visualizing the
      three-dimensional landscape of preferred pathways for the transfer of unpaired
      spin density from a paramagnetic metal center onto the protein frame, and will
      discriminate specific interactions by a "through-bond" mechanism from
      interactions which are "through-space" in various metalloproteins.

PMID- 23145463
TI  - Long bone fracture as a complication following external skeletal fixation: 11
      cases.
AB  - OBJECTIVES: To report on a series of dogs and cats with long bone fractures that
      occurred as a direct consequence of linear external skeletal fixation (ESF)
      application. METHODS: Retrospective study. Data from the medical records and
      radiographs of canine (n = 4) and feline (n = 7) cases were collected from three
      referral and three first opinion practices in the UK (1999 to 2011). RESULTS:
      Long bone fractures occurred following the application of linear ESF either while
      the ESF was in situ or after removal. All fractures occurred through either a pin
      tract or an empty drill hole. Pins associated with ESF-related fracture tended to
      be in the higher end of the recommended size range. The majority of cases had
      additional complicating factors such as multiple injuries, revision surgery, poor
      owner compliance with postoperative exercise restriction and the presence of
      empty drill holes. CLINICAL SIGNIFICANCE: In cases with features that could
      complicate outcome, careful attention should be paid to recommendations for ESF
      application. Leaving empty drill holes is suboptimal. The retrospective nature of
      the study, low numbers of, and diversity amongst, cases should be taken into
      consideration when interpreting the results from this study.

PMID- 23145462
TI  - Single-molecule imaging and functional analysis of Als adhesins and mannans
      during Candida albicans morphogenesis.
AB  - Cellular morphogenesis in the fungal pathogen Candida albicans is associated with
      changes in cell wall composition that play important roles in biofilm formation
      and immune responses. Yet, how fungal morphogenesis modulates the biophysical
      properties and interactions of the cell surface molecules is poorly understood,
      mainly owing to the paucity of high-resolution imaging techniques. Here, we use
      single-molecule atomic force microscopy to localize and analyze the key
      components of the surface of living C. albicans cells during morphogenesis. We
      show that the yeast-to-hypha transition leads to a major increase in the
      distribution, adhesion, unfolding, and extension of Als adhesins and their
      associated mannans on the cell surface. We also find that morphogenesis
      dramatically increases cell surface hydrophobicity. These molecular changes are
      critical for microbe-host interactions, including adhesion, colonization, and
      biofilm formation. The single-molecule experiments presented here offer promising
      prospects for understanding how microbial pathogens use cell surface molecules to
      modulate biofilm and immune interactions.

PMID- 23145464
TI  - Protective effects of melatonin against oxidative injury in rat testis induced by
      wireless (2.45 GHz) devices.
AB  - Wireless devices have become part of everyday life and mostly located near
      reproductive organs while they are in use. The present study was designed to
      determine the possible protective effects of melatonin on oxidative stress
      dependent testis injury induced by 2.45-GHz electromagnetic radiation (EMR).
      Thirty-two rats were equally divided into four different groups, namely cage
      control (A1), sham control (A2), 2.45-GHz EMR (B) and 2.45-GHz EMR+melatonin (C).
      Group B and C were exposed to 2.45-GHz EMR during 60 min day(-1) for 30 days.
      Lipid peroxidation levels were higher in Group B than in Group A1 and A2.
      Melatonin treatment prevented the increase in the lipid peroxidation induced by
      EMR. Also reduced glutathione (GSH) and glutathione peroxidase (GSH-Px) levels in
      Group D were higher than that of exposure group. Vitamin A and E concentrations
      decreased in exposure group, and melatonin prevented the decrease in vitamin E
      levels. In conclusion, wireless (2.45 GHz) EMR caused oxidative damage in testis
      by increasing the levels of lipid peroxidation and decreasing in vitamin A and E
      levels. Melatonin supplementation prevented oxidative damage induced by EMR and
      also supported the antioxidant redox system in the testis. 

PMID- 23145465
TI  - S(N)2' reaction of allylic difluorides with lithium amides and thiolates.
AB  - The synthesis of monofluoroalkenes using an S(N)2' reaction of lithium amides
      derived from aromatic amines or lithium thiolates with 3,3-difluoropropenes is
      reported. This transformation features the use of fluoride as a leaving group.

PMID- 23145466
TI  - Composite graft for nostril margin reconstruction.

PMID- 23145467
TI  - Synthesis of diarylmethanes via metal-free reductive cross-coupling of
      diarylborinic acids with tosyl hydrazones.
AB  - This paper describes a practical and efficient procedure that takes advantage of
      diarylborinic acids as a cost-effective alternative to arylboronic acids for
      synthesis of diarylmethanes through metal-free reductive cross-coupling with N
      tosylhydrazones of aromatic aldehydes and ketones. The procedure tolerates
      hydroxyl, halide, amine, and allyl functionality, complementary to the transition
      metal catalyzed cross-coupling techniques.

PMID- 23145468
TI  - Quality of root fillings performed with two root filling techniques. An in vitro
      study using micro-CT.
AB  - OBJECTIVE: The aim of this study was to compare the presence of voids in root
      fillings performed in oval and ribbon-shaped canals with two root filling
      techniques, lateral compaction technique (LCT) or hybrid technique (HT), a
      combination of a gutta-percha masterpoint and thermoplastic gutta-percha.
      Furthermore, the obturation time for the two techniques was evaluated. MATERIALS
      AND METHODS: Sixty-seven roots with oval and ribbon-shaped canals were prepared
      using Profile Ni-Ti rotary files. After preparation, the roots were randomly
      allocated to two groups according to root filling technique. All roots were
      filled with AH plus and gutta-percha. Group 1 was filled using LCT (n = 34) and
      group 2 was filled using HT (n = 33). The obturation time was measured in 30
      cases evenly distributed between the two techniques. Voids in relation to the
      root canal fillings were assessed using cross-section images from Micro-computed
      Tomography scans. RESULTS: All root canal fillings had voids. Permutation test
      showed no statistically significant difference between the two root filling
      techniques in relation to presence of voids (p = 0.092). A statistically
      significant difference in obturation time between the two techniques was found (p
      < 0.001). CONCLUSION: The present study found no statistically significant
      difference in percentage of voids between two root filling techniques. A 40%
      reduction in obturation time was found for the HT compared to the LCT.

PMID- 23145469
TI  - Efficacy of ivermectin versus dual infections of Haemonchus contortus and
      Heligmosomoides polygyrus in the mouse.
AB  - This report describes a novel assay for the detection of gastrointestinal
      anthelmintics using mice infected with Haemonchus contortus and adapted to the 1
      animal/test group protocol. Mice infected with both H. contortus and
      Heligmosomoides polygyrus were fed ivermectin-medicated diets for 6 days. A
      dietary level of 0.09375 ppm was 98.1% effective against the 0- to 6-day-old
      abomasal stomach worm of sheep, whereas a level of 0.75 ppm reduced the 3- to 9
      day-old H. polygyrus worm burden by 94.0%. H. contortus was approximately 8-fold
      more sensitive to ivermectin than was H. polygyrus in this model. The sensitivity
      of this assay rivals that of the gerbil-Trichostrongylus colubriformis model
      while utilizing a more economical host.

PMID- 23145471
TI  - Long-term (12-month) improvement in meibomian gland function and reduced dry eye
      symptoms with a single thermal pulsation treatment.
AB  - PURPOSE: To determine the 1-year post-treatment dry eye status of subjects with
      meibomian gland dysfunction and dry eye symptoms after receiving a single
      LipiFlow Thermal Pulsation System treatment. DESIGN: Single-centre, prospective,
      observational, open-label, 1-month-registered clinical trial with a 1-year follow
      up examination. PARTICIPANTS: Patients with evaporative dry eye disease with
      meibomian gland dysfunction and dry eye symptoms who had participated in the
      registered 1-month clinical trial. METHODS: Eighteen of 30 subjects initially
      enrolled were able to return for a 1-year follow-up. Both eyes of all patients
      were treated with a single 12-min treatment using the LipiFlow Thermal Pulsation
      System. Meibomian gland function, tear break-up time and dry eye symptoms were
      measured. Data are presented for pretreatment (baseline), and 1-month and 1-year
      post-treatment. MAIN OUTCOME MEASURES: Meibomian gland secretion scores, and tear
      break-up time and dry eye symptoms. RESULTS: Significant improvement in meibomian
      gland secretion scores from baseline measurements (4.0 +/- 3.4) to 1-month post
      treatment (11.3 +/- 4.7; P < 0.0005) was maintained at 1-year (7.3 +/- 4.6; P <
      0.05). Baseline tear break-up time (4.9 +/- 3.0) was significantly increased at 1
      month (9.5 +/- 6.9; P < 0.05); however, this improvement was no longer evident at
      1-year post-treatment (6.0 +/- 4.4). The significant improvement in symptom
      scores on Ocular Surface Disease Index and Standard Patient Evaluation of Eye
      Dryness questionnaires observed at 1-month (P < 0.0005) was maintained at 1-year
      (Ocular Surface Disease Index [P < 0.05]; Standard Patient Evaluation of Eye
      Dryness [P < 0.0005]). CONCLUSION: A single 12-min treatment with the Lipi Flow
      Thermal Pulsation System offers an effective treatment for evaporative dry eye
      and meibomian gland dysfunction resulting in significant and sustained
      improvement in signs and symptoms for up to 1 year.

PMID- 23145470
TI  - Evolutionary study of duplications of the miRNA machinery in aphids associated
      with striking rate acceleration and changes in expression profiles.
AB  - BACKGROUND: The sequencing of the genome of the pea aphid Acyrthosiphon pisum
      revealed an unusual expansion of the miRNA machinery, with two argonaute-1, two
      dicer-1 and four pasha gene copies. In this report, we have undertaken a deeper
      evolutionary analysis of the phylogenetic timing of these gene duplications and
      of the associated selective pressures by sequencing the two copies of ago-1 and
      dcr-1 in different aphid species of the subfamily Aphidinae. We have also carried
      out an analysis of the expression of both copies of ago-1 and dcr-1 by semi
      quantitative PCR in different morphs of the pea aphid life cycle. RESULTS: The
      analysis has shown that the duplication of ago-1 occurred in an ancestor of the
      subfamily Aphidinae while the duplication of dcr-1 appears to be more recent.
      Besides, it has confirmed a pattern of one conserved copy and one accelerated
      copy for both genes, and has revealed the action of positive selection on several
      regions of the fast-evolving ago-1b. On the other hand, the semi-quantitative PCR
      experiments have revealed a differential expression of these genes between the
      morphs of the parthenogenetic and the sexual phases of Acyrthosiphon pisum.
      CONCLUSIONS: The discovery of these gene duplications in the miRNA machinery of
      aphids opens new perspectives of research about the regulation of gene expression
      in these insects. Accelerated evolution, positive selection and differential
      expression affecting some of the copies of these genes suggests the possibility
      of a neofunctionalization of these duplicates, which might play a role in the
      display of the striking phenotypic plasticity of aphids.

PMID- 23145472
TI  - Involvement of auxin pathways in modulating root architecture during beneficial
      plant-microorganism interactions.
AB  - A wide variety of microorganisms known to produce auxin and auxin precursors form
      beneficial relationships with plants and alter host root development. Moreover,
      other signals produced by microorganisms affect auxin pathways in host plants.
      However, the precise role of auxin and auxin-signalling pathways in modulating
      plant-microbe interactions is unknown. Dissecting out the auxin synthesis,
      transport and signalling pathways resulting in the characteristic molecular,
      physiological and developmental response in plants will further illuminate upon
      how these intriguing inter-species interactions of environmental, ecological and
      economic significance occur. The present review seeks to survey and summarize the
      scattered evidence in support of known host root modifications brought about by
      beneficial microorganisms and implicate the role of auxin synthesis, transport
      and signal transduction in modulating beneficial effects in plants. Finally,
      through a synthesis of the current body of work, we present outstanding
      challenges and potential future research directions on studies related to auxin
      signalling in plant-microbe interactions.

PMID- 23145473
TI  - Automation of the CHARMM General Force Field (CGenFF) II: assignment of bonded
      parameters and partial atomic charges.
AB  - Molecular mechanics force fields are widely used in computer-aided drug design
      for the study of drug candidates interacting with biological systems. In these
      simulations, the biological part is typically represented by a specialized
      biomolecular force field, while the drug is represented by a matching general
      (organic) force field. In order to apply these general force fields to an
      arbitrary drug-like molecule, functionality for assignment of atom types,
      parameters, and partial atomic charges is required. In the present article,
      algorithms for the assignment of parameters and charges for the CHARMM General
      Force Field (CGenFF) are presented. These algorithms rely on the existing
      parameters and charges that were determined as part of the parametrization of the
      force field. Bonded parameters are assigned based on the similarity between the
      atom types that define said parameters, while charges are determined using an
      extended bond-charge increment scheme. Charge increments were optimized to
      reproduce the charges on model compounds that were part of the parametrization of
      the force field. A "penalty score" is returned for every bonded parameter and
      charge, allowing the user to quickly and conveniently assess the quality of the
      force field representation of different parts of the compound of interest. Case
      studies are presented to clarify the functioning of the algorithms and the
      significance of their output data.

PMID- 23145474
TI  - Photoselective vaporization with the green light laser vs transurethral resection
      of the prostate for treating benign prostate hyperplasia: a systematic review and
      meta-analysis.
AB  - OBJECTIVE: To assess the overall efficacy and safety of photoselective
      vaporization of the prostate (PVP) vs transurethral resection of the prostate
      (TURP) for treating patients with lower urinary tract symptoms (LUTS) secondary
      to benign prostate hyperplasia (BPH). PATIENTS AND METHODS: A systematic search
      of the electronic databases, including MEDLINE, Embase, Web of Science and The
      Cochrane Library, as well as manual bibliography searches were performed. The
      pooled estimates of maximum flow rate (Q(max)), postvoid residual (PVR), quality
      of life (QoL), International Prostate Symptom Score (IPSS), operation duration,
      blood loss, catheterization time, hospital stay, capsule perforation,
      transfusion, transurethral resection (TUR) syndrome, urethral stricture and
      reintervention were calculated. RESULTS: At the 3-month follow-up, there was no
      significant difference in Q(max), PVR, QoL and IPSS between the TURP and PVP
      groups. At the 6-month follow-up, the pooled QoL favoured TURP, but there was no
      significant difference in the other variables between the two groups. PVP was
      associated with less blood loss, transfusion, capsular perforation, TUR syndrome,
      shorter catheterization time and hospital stay, but longer operation duration and
      higher reintervention rate. CONCLUSIONS: The efficacy of PVP was similar to that
      of TURP in relation to Q(max), PVR, QoL and IPSS, and it offered several
      advantages over TURP. As a promising minimal invasive technique, PVP could be
      used as an alternative surgical procedure for treating BPH.

PMID- 23145475
TI  - Redox-stimulated motion and bistability in metal complexes and organometallic
      compounds.
AB  - SIGNIFICANCE: Control over reversible changes to molecular structure forms the
      basis for artificial molecular machines that could eventually lead to the
      development of molecule-based nanotechnology. RECENT ADVANCES: Particular
      applications in information storage and processing could emerge where the
      structural rearrangements give rise to bistability and molecular hysteresis
      effects. CRITICAL ISSUES: Oxidation-state-dependent coordination and bonding
      preferences in transition metal complexes and organometallic compounds provide a
      versatile approach to the control of molecular motions by redox input, but so
      far, few structural motifs have been applied in redox-actuated molecular
      machines. FUTURE DIRECTIONS: Further progress toward molecule-based nanoscale
      devices might be accomplished with molecular components derived from a wider
      range of structural themes and forms of molecular motion. Examples of redox
      stimulated rearrangements in metal complexes and organometallic compounds are
      described that have been employed in molecular machines or could be considered
      for the design of new functional molecules.

PMID- 23145476
TI  - Real-time observation of nanosecond liquid-phase assembly of nickel nanoparticles
      via pulsed-laser heating.
AB  - Using pump-probe electron microscopy techniques, the dewetting of thin nickel
      films exposed to a pulsed nanosecond laser was monitored at tens of nanometers
      spatial and nanosecond time scales to provide insight into the liquid-phase
      assembly dynamics. Thickness-dependent and correlated time and length scales
      indicate that a spinodal instability drives the assembly process. Measured
      lifetimes of the liquid metal are consistent with finite-difference simulations
      of the laser-irradiated film and are consistent with estimated and observed
      spinodal time scales. These results can be used to design improved synthesis and
      assembly routes toward achieving advanced functional nanomaterials and devices.

PMID- 23145477
TI  - Is gender policy related to the gender gap in external cause and circulatory
      disease mortality? A mixed effects model of 22 OECD countries 1973-2008.
AB  - BACKGROUND: Gender differences in mortality vary widely between countries and
      over time, but few studies have examined predictors of these variations, apart
      from smoking. The aim of this study is to investigate the link between gender
      policy and the gender gap in cause-specific mortality, adjusted for economic
      factors and health behaviours. METHODS: 22 OECD countries were followed 1973-2008
      and the outcomes were gender gaps in external cause and circulatory disease
      mortality. A previously found country cluster solution was used, which includes
      indicators on taxes, parental leave, pensions, social insurances and social
      services in kind. Male breadwinner countries were made reference group and
      compared to earner-carer, compensatory breadwinner, and universal citizen
      countries. Specific policies were also analysed. Mixed effect models were used,
      where years were the level 1-units, and countries were the level 2-units.
      RESULTS: Both the earner-carer cluster (ns after adjustment for GDP) and policies
      characteristic of that cluster are associated with smaller gender differences in
      external causes, particularly due to an association with increased female
      mortality. Cluster differences in the gender gap in circulatory disease mortality
      are the result of a larger relative decrease of male mortality in the
      compensatory breadwinner cluster and the earner-carer cluster. Policies
      characteristic of those clusters were however generally related to increased
      mortality. CONCLUSION: Results for external cause mortality are in concordance
      with the hypothesis that women become more exposed to risks of accident and
      violence when they are economically more active. For circulatory disease
      mortality, results differ depending on approach--cluster or indicator. Whether
      cluster differences not explained by specific policies reflect other welfare
      policies or unrelated societal trends is an open question. Recommendations for
      further studies are made.

PMID- 23145478
TI  - SIMPLE LEAF3 encodes a ribosome-associated protein required for leaflet
      development in Cardamine hirsuta.
AB  - Leaves show considerable variation in shape, and may be described as simple, when
      the leaf is entire, or dissected, when the leaf is divided into individual
      leaflets. Here, we report that the SIMPLE LEAF3 (SIL3) gene is a novel
      determinant of leaf shape in Cardamine hirsuta - a dissected-leaved relative of
      the simple-leaved model species Arabidopsis thaliana. We show that SIL3 is
      required for leaf growth and leaflet formation but leaf initiation is less
      sensitive to perturbation of SIL3 activity. SIL3 is further required for KNOX
      (knotted1-like homeobox) gene expression and localized auxin activity maxima,
      both of which are known to promote leaflet formation. We cloned SIL3 and showed
      that it encodes RLI2 (RNase L inhibitor 2), an ATP binding cassette-type ATPase
      with important roles in ribosome recycling and translation termination that are
      conserved in eukaryotes and archaea. RLI mutants have not been described in
      plants to date, and this paper highlights the potential of genetic studies in C.
      hirsuta to uncover novel gene functions. Our data indicate that leaflet
      development is sensitive to perturbation of RLI2-dependent aspects of cellular
      growth, and link ribosome function with dissected-leaf development.

PMID- 23145479
TI  - Sports officials' hearing status: whistle use as a factor contributing to hearing
      trouble.
AB  - The objectives of this study were to examine the prevalence of hearing loss in a
      sample of sports officials and estimate the duration of whistle use required to
      reach a permissible 8-hr 100% noise dose. We conducted an online survey of 321
      sports officials regarding their exposure to whistle noise and symptoms of
      hearing loss and tinnitus, and we assessed the acoustic characteristics of
      commercially available whistles. Male sports officials registered in Michigan had
      a greater prevalence of self-reported hearing trouble and tinnitus than observed
      in the general population of the midwestern United States. Sound levels produced
      by whistles range between 104 and 116 dBA, which corresponds to maximum
      unprotected exposure times of 90 to 5 sec, respectively. These findings suggest
      that whistle use may contribute to hearing loss among sports officials.

PMID- 23145481
TI  - Spectroscopic study on the structural differences of thermally induced cross
      linking segments in emeraldine salt and base forms of polyaniline.
AB  - This paper reports the spectroscopic study on the structural differences of
      thermally induced cross-linking segments in polyaniline in its emeraldine salt
      (PANI-ES) and base (PANI-EB) forms. Casting films of PANI-ES (ES-film) and PANI
      EB (EB-film) were prepared and heated at 150  degrees C under atmospheric air for
      30 min. Raman spectra excited at 632.8 nm of heated ES-film presented the
      characteristic bands of phenazine-like structures at 1638, 1392, and 575 cm(-1),
      whereas EB-film showed lower relative intensities for these bands. The lower
      content of phenazine-like segments in heated EB-film is related to residual
      polaronic segments from preparation procedures, as revealed by Raman. This
      statement was confirmed by a sequence of thermal and doping experiments in both
      films. Quantum-chemical calculations by density functional theory (DFT) and time
      dependent density functional theory (TD-DFT) showed that the phenazine-like
      structure presents the intense Raman band at 1350 cm(-1) due to heterocycle
      breathing mode, and the non-phenazine-like structure (substituted hydrophenazine
      type) presents higher energy for HOMO-LUMO transition, indicating the lack of
      conjugation in the heterocycle compared with the phenazine-like structure.
      According to experimental and theoretical data reported here, it is proposed that
      only thermally treated PANI-ES presents phenazine-like rings, whereas PANI-EB
      presents heterocyclic non-aromatic structures.

PMID- 23145482
TI  - Nocebo as a potential confounding factor in clinical trials for Parkinson's
      disease treatment: a meta-analysis.
AB  - BACKGROUND AND PURPOSE: Nocebo refers to adverse events (AEs) generated by
      patient's negative expectations that medical treatment will likely harm instead
      of heal and can be assessed in placebo-controlled randomized controlled trials
      (RCTs). We examined AEs following placebo administration in RCTs for Parkinson's
      disease (PD). METHODS: After a systematic Medline search for RCTs for PD
      pharmacologic treatments published between 2000 and 2010, we assessed percentages
      of placebo-treated patients reporting at least one AE or discontinuing due to
      placebo intolerance and searched for factors influencing nocebo's extent.
      RESULTS: Data were extracted from 41 RCTs fulfilling search criteria. Of 3544
      placebo-treated patients, 64.7% (95% CI: 53.6-74.4) reported at least one AE and
      8.8% (95% CI: 6.8-11.5) discontinued placebo treatment due to intolerance. The
      number of AEs per 100 person-months was 25.9 (95% CI: 16.8-39.8). Nocebo dropout
      rate was positively related to study population size and year of publication.
      Increased number of AEs per 100 person-months was negatively correlated with the
      duration of treatment. AE rates, dropout rates, and AEs per 100 person-months in
      placebo- and active drug-treated patients were strongly correlated (r = 0.941,
      0.695, and 0.824, respectively). CONCLUSIONS: Our analysis indicates a
      significant dropout rate related to nocebo in trials for PD treatment. Adherence
      and efficacy may be adversely affected with additional implications for clinical
      practice.

PMID- 23145483
TI  - Structural determination of glucosylceramides in the distillation remnants of
      shochu, the Japanese traditional liquor, and its production by Aspergillus
      kawachii.
AB  - Shochu is traditional Japanese liquor produced from various crops and fungi
      Aspergillus kawachi or A. awamorii . The amount of unutilized shochu distillation
      remnants is increasing because of the recent prohibition of ocean dumping of
      these remnants. In this Article, we first describe the structures of
      glucosylceramides contained in shochu distillation remnants by fragment ion
      analysis using ESI-tandem mass spectrometry. Shochu distillation remnant produced
      from barley contained glucosylceramides d18:2/C16:0h, d18:2/C20:0h, d19:2/C18:1h,
      and d18:2/C18:0h. Koji (barley fermented with A. kawachii) contained the same
      glucosylceramides. Shochu distillation remnants produced from rice contained
      glucosylceramides d18:2/C18:0h and d19:2/C18:1h. The culture broth of A. kawachii
      contained glucosylceramides d19:2/C18:1h and d19:2/C18:0h. These results indicate
      that the glucosylceramides contained in crops and those produced by A. kawachii
      transfer through the processes of fermentation with yeast and distillation to the
      shochu distillation remnant. This information will enable utilization of shochu
      distillation remnants and koji as novel sources of sphingolipids.

PMID- 23145484
TI  - Toxoplasma gondii in ruminant species (cattle, sheep, and goats) from southern
      Spain.
AB  - Seroprevalences of Toxoplasma gondii antibodies were assessed with the use of a
      commercial indirect ELISA in 1,501 domestic ruminants in southern Spain.
      Antibodies against T. gondii were detected in 420 (83.3%) of 504 cattle, 248
      (49.3%) of 503 sheep, and 124 (25.1%) of 494 goats. The herd seroprevalence was
      100% (72/72), 84.7% (61/72), and 72.2% (52/72) for cattle, sheep, and goats,
      respectively. Seropositivity was significantly higher in herds with a low density
      of animals (P < 0.001). Significant differences (P < 0.05) among municipalities
      were also found. The seroprevalence observed in the present study indicates a
      widespread exposure to T. gondii in livestock in southern Spain.

PMID- 23145480
TI  - TRPV1 and SP: key elements for sepsis outcome?
AB  - Sensory neurons play important roles in many disorders, including inflammatory
      diseases, such as sepsis. Sepsis is a potentially lethal systemic inflammatory
      reaction to a local bacterial infection, affecting thousands of patients
      annually. Although associated with a high mortality rate, sepsis outcome depends
      on the severity of systemic inflammation, which can be directly influenced by
      several factors, including the immune response of the patient. Currently, there
      is a lack of effective drugs to treat sepsis, and thus there is a need to develop
      new drugs to improve sepsis outcome. Several mediators involved in the formation
      of sepsis have now been identified, but the mechanisms underlying the pathology
      remain poorly understood. The transient receptor potential vanilloid 1 (TRPV1)
      receptor and the neuropeptide substance P (SP) have recently been demonstrated as
      important targets for sepsis and are located on sensory neurones and non-neuronal
      cells. Herein, we highlight and review the importance of sensory neurones for the
      modulation of sepsis, with specific focus on recent findings relating to TRPV1
      and SP, with their distinct abilities to alter the transition from local to
      systemic inflammation and also modify the overall sepsis outcome. We also
      emphasize the protective role of TRPV1 in this context. LINKED ARTICLES: This
      article is part of a themed section on Neuropeptides. To view the other articles
      in this section visit http://dx.doi.org/10.1111/bph.2013.170.issue-7.

PMID- 23145486
TI  - Using molecular simulation to understand the structure of [C2C1im]+-alkylsulfate
      ionic liquids: bulk and liquid-vapor interfaces.
AB  - Using molecular dynamics simulations we have studied the structure of
      alkylsulfate-based ionic liquids: 1-ethyl-3-methylimidazolium n-alkylsulfate
      [C(2)C(1)im][C(n)SO(4)] (n = 2, 4, 6 and 8). The structure of the different ionic
      liquids have been interpreted taking into account radial and spatial distribution
      functions, and structure factors, that allowed us to characterize the morphology
      of the polar and nonpolar domains present in this family of liquids. The size of
      the nonpolar regions depends linearly on the anion alkyl chain length.
      Furthermore, properties of the surface of ionic liquids, such as surface tension,
      ordering, and charge and density profiles, were studied using molecular
      simulation. We were able to reproduce the experimental values of the surface
      tension with a maximum deviation of 10%, and it was possible to relate the values
      of the surface tension with the structure of the liquid-vacuum interfaces.
      Microscopic structural analysis of orientational ordering at the interface and
      density profiles along the direction normal to the interface suggest that the
      alkyl chains of the anions tend to protrude toward the vacuum, and the presence
      of the interface leads to a strong organization of the liquid phase in the region
      close to the interface, stronger when the side-chain length of the anions
      increases.

PMID- 23145485
TI  - Influence of attachment and bone loss on the mobility of incisors and canine
      teeth.
AB  - OBJECTIVE: The purpose of this clinical study was to evaluate the correlation
      between tooth mobility (TM), crown-to-root ratio (CRR) and clinical attachment
      loss (CAL) in periodontally-compromised participants. MATERIALS AND METHODS:
      While slowly biting on a load cell, the mobility of the upper incisors and canine
      teeth of 20 volunteers was measured using a photogrammetric measurement
      technique. An automated software program recorded the force-related three
      dimensional TM at 3-N intervals. CAL was assessed clinically and CRR values were
      assessed radiographically. For each contralateral pair of teeth (central, lateral
      incisor, canine) and for each main level of force, the Pearson product-moment
      correlation coefficient between TM and CRR and between TM and CAL was computed.
      Correlations were considered statistically significant at p < 0.05. RESULTS:
      Statistically significant positive correlations were found between TM and CRR for
      incisors and canines for each main level of force, whereas canines had the lowest
      correlation. Statistically significant positive correlations were also found
      between TM and CAL for the central and lateral incisors at each main level of
      force. Canines showed no significant correlation between CAL and TM, regardless
      of force level. CONCLUSION: The loss of attachment and bone seem to have more
      influence on the mobility of incisors than canines.

PMID- 23145487
TI  - A descriptive study of reportable gastrointestinal illnesses in Ontario, Canada,
      from 2007 to 2009.
AB  - BACKGROUND: Gastrointestinal illnesses (GI) continue to pose a substantial burden
      in terms of morbidity and economic impact in Canada. We describe the epidemiology
      of reportable GI in Ontario by characterizing the incidence of each reportable
      GI, as well as associated demographics, clinical outcomes, seasonality, risk
      settings, and likely sources of infection. METHODS: Reports on laboratory
      confirmed cases of amebiasis, botulism, campylobacteriosis, cryptosporidiosis,
      cyclosporiasis, giardiasis, hepatitis A, listeriosis, paratyphoid fever,
      salmonellosis, shigellosis, typhoid fever, illness due to verotoxin-producing
      Escherichia coli (VTEC-illness), and yersiniosis, from January 1, 2007 to
      December 31, 2009 were obtained from Ontario's passive reportable disease
      surveillance system. Cases were classified by history of relevant travel,
      association with outbreaks, and likely source of infection, obtained through
      follow-up of reported cases by local health authorities. RESULTS: There were
      29,897 GI reported by health authorities in Ontario from 2007 to 2009. The most
      frequently reported diseases were campylobacteriosis (10,916 cases or 36.5% of
      all GI illnesses) and salmonellosis (7,514 cases, 25.1%). Overall, 26.9% of GI
      cases reported travel outside of Ontario during the relevant incubation period.
      Children four years of age and younger had the highest incidence rate for most
      GI, and significantly more (54.8%, p<0.001) cases occurred among males than
      females. The most commonly reported sources of infections were food (54.2%),
      animals (19.8%), and contact with ill persons (16.9%). Private homes (45.5%) and
      food premises (29.7%) were the most commonly reported exposure settings. Domestic
      cases of campylobacteriosis, cryptosporidiosis, giardiasis, salmonellosis, and
      VTEC-illness showed seasonal patterns with incidence peaking in the summer
      months. CONCLUSIONS: Reportable GI continues to be a burden in Ontario. Since
      more than one in four GI cases experienced in Ontario were acquired outside of
      the province, international travel is an important risk factor for most GI.
      Because private homes are the most commonly reported risk settings and the main
      suspect sources of infection are food, animal contact and ill persons, these
      findings support the continued need for public health food safety programs,
      public education on safe handling of food and animals, and proper hand hygiene
      practices.

PMID- 23145488
TI  - Evolutionary analyses of non-family genes in plants.
AB  - There are a large number of 'non-family' (NF) genes that do not cluster into
      families with three or more members per genome. While gene families have been
      extensively studied, a systematic analysis of NF genes has not been reported. We
      performed comparative studies on NF genes in 14 plant species. Based on the
      clustering of protein sequences, we identified ~94,000 NF genes across these
      species that were divided into five evolutionary groups: Viridiplantae wide,
      angiosperm specific, monocot specific, dicot specific, and those that were
      species specific. Our analysis revealed that the NF genes resulted largely from
      less frequent gene duplications and/or a higher rate of gene loss after segmental
      duplication relative to genes in both low-copy-number families (LF; 3-10 copies
      per genome) and high-copy-number families (HF; >10 copies). Furthermore, we
      identified functions enriched in the NF gene set as compared with the HF genes.
      We found that NF genes were involved in essential biological processes shared by
      all plant lineages (e.g. photosynthesis and translation), as well as gene
      regulation and stress responses associated with phylogenetic diversification. In
      particular, our analysis of an Arabidopsis protein-protein interaction network
      revealed that hub proteins with the top 10% most connections were over
      represented in the NF set relative to the HF set. This research highlights the
      roles that NF genes may play in evolutionary and functional genomics research.

PMID- 23145489
TI  - Protein evolution in two co-occurring types of Symbiodinium: an exploration into
      the genetic basis of thermal tolerance in Symbiodinium clade D.
AB  - BACKGROUND: The symbiosis between reef-building corals and photosynthetic
      dinoflagellates (Symbiodinium) is an integral part of the coral reef ecosystem,
      as corals are dependent on Symbiodinium for the majority of their energy needs.
      However, this partnership is increasingly at risk due to changing climatic
      conditions. It is thought that functional diversity within Symbiodinium may allow
      some corals to rapidly adapt to different environments by changing the type of
      Symbiodinium with which they partner; however, very little is known about the
      molecular basis of the functional differences among symbiont groups. One group of
      Symbiodinium that is hypothesized to be important for the future of reefs is
      clade D, which, in general, seems to provide the coral holobiont (i.e., coral
      host and associated symbiont community) with elevated thermal tolerance. Using
      high-throughput sequencing data from field-collected corals we assembled, de
      novo, draft transcriptomes for Symbiodinium clades C and D. We then explore the
      functional basis of thermal tolerance in clade D by comparing rates of coding
      sequence evolution among the four clades of Symbiodinium most commonly found in
      reef-building corals (A-D). RESULTS: We are able to highlight a number of genes
      and functional categories as candidates for involvement in the increased thermal
      tolerance of clade D. These include a fatty acid desaturase, molecular chaperones
      and proteins involved in photosynthesis and the thylakoid membrane. We also
      demonstrate that clades C and D co-occur within most of the sampled colonies of
      Acropora hyacinthus, suggesting widespread potential for this coral species to
      acclimatize to changing thermal conditions via 'shuffling' the proportions of
      these two clades from within their current symbiont communities. CONCLUSIONS:
      Transcriptome-wide analysis confirms that the four main Symbiodinium clades found
      within corals exhibit extensive evolutionary divergence (18.5-27.3% avg. pairwise
      nucleotide difference). Despite these evolutionary distinctions, many corals
      appear to host multiple clades simultaneously, which may allow for rapid
      acclimatization to changing environmental conditions. This study provides a first
      step toward understanding the molecular basis of functional differences between
      Symbiodinium clades by highlighting a number of genes with signatures consistent
      with positive selection along the thermally tolerant clade D lineage.

PMID- 23145491
TI  - Bias-enhanced optical pH response of group III-nitride nanowires.
AB  - We show that the photoluminescence intensity of GaN and InGaN nanowires in
      electrolytes sensitively responds to variations of the pH value and the applied
      bias. The realization of an electrochemical working point allows pH detection
      with a resolution better than 0.05 pH. The observed effects are attributed to
      bias-dependent nonradiative recombination processes competing with interband
      transitions. The results show that group III-nitride nanowires are excellently
      suited as nanophotonic pH sensor elements.

PMID- 23145490
TI  - Endometrial adenocarcinoma in two young queens.
AB  - Endometrial adenocarcinoma is described in two young intact female Persian cats
      presented with haemorrhagic vaginal discharge. The discharge had been present for
      3 and 15 days in each case, respectively. On the basis of signalment, history,
      clinical, laboratory and diagnostic imaging findings a tentative diagnosis of
      pyometra was made in each cat and ovariohysterectomy was subsequently performed.
      Histological examination revealed endometrial adenocarcinoma in both cats
      together with ovarian luteal cysts and pyometra in one case. Immunohistochemistry
      revealed a diffuse and strongly positive reaction for oestrogen receptors in the
      nuclei of glandular epithelium in well-differentiated areas of the neoplastic
      tissue. Poorly differentiated areas of solid growth pattern had weak and focal
      expression of oestrogen receptors. Furthermore, the neoplastic cells within these
      areas displayed moderate to strong diffuse nuclear staining with Ki-67 antibody
      suggestive of a high proliferative capacity. The owners reported that the cats
      were clinically healthy 23 and 21 months after the surgery. These cases highlight
      the importance of histological examination of surgically resected tissue even
      when clinical signs and laboratory findings suggest pyometra.

PMID- 23145492
TI  - Rhenium-catalyzed regio- and stereoselective synthesis of gamma-thio-alpha,beta
      unsaturated ketones via insertion of terminal alkynes into the C-S bond.
AB  - The reaction of alpha-thioketones and alkynes in the presence of a rhenium
      catalyst, [HRe(CO)(4)](n), gave gamma-thio-alpha,beta-unsaturated ketones in
      excellent yields. The alkynes were inserted into the carbon-sulfur bond of the
      alpha-thioketones, and isomerization of a double bond provided the products with
      high regio- and stereoselectivities. This reaction also proceeded in an
      intramolecular fashion.

PMID- 23145494
TI  - Solar UV exposure at eye is different from environmental UV: diurnal monitoring
      at different rotation angles using a manikin.
AB  - Solar ultraviolet radiation (UVR) promotes pterygium and cataract development in
      the human eye. When outdoors, people are subject to varying ocular UVR exposure
      intensity depending on time of day and orientation to the sun. To assess this
      variability, a manikin eye was exposed to solar UVR at 12 rotation angles
      relative to the sun with a solar elevation angle (SEA) ranging from 24.6 degrees 
      to 88.2 degrees . At rotation angles of 0 degrees , 30 degrees , and 330 degrees
      , the diurnal variation of ocular UVR exposure intensity showed a bimodal
      distribution that peaked at a SEA of about 40 degrees , which was 3 to 4 hr both
      before and after noon. This timing differed from peak environmental UVR exposure
      intensity. At the other rotation angles, diurnal variations in ocular UV exposure
      exhibited unimodal curves, with maximum intensity around noon, the same as for
      environmental UVR. Thus, the idea that UVR exposure is most intense at midday is
      true for skin surfaces positioned somewhat horizontally but not for the eyes in a
      60 degrees  arc with a centerline toward the sun (i.e., ranging 30 degrees 
      clockwise or counter-clockwise from the centerline). Maintaining certain
      orientations relative to the sun's position (for example, being clockwise or
      counter-clockwise by 30 degrees  from the sun) should effectively reduce ocular
      UVR exposure, especially at times when the SEA is 40 degrees .

PMID- 23145493
TI  - The gasotransmitter hydrogen sulfide induces nrf2-target genes by inactivating
      the keap1 ubiquitin ligase substrate adaptor through formation of a disulfide
      bond between cys-226 and cys-613.
AB  - AIMS: The signaling molecule hydrogen sulfide (H2S) protects cells against
      oxidative stress and activates NF-E2 p45-related factor 2 (Nrf2), a transcription
      factor that regulates antioxidant genes. We sought to establish whether H2S
      requires Nrf2 to protect against oxidative stress, and whether activation of Nrf2
      by H2S involves antagonism of Kelch-like ECH-associated protein-1 (Keap1), a
      redox-sensitive ubiquitin ligase substrate adaptor that represses Nrf2 under
      normal homeostatic conditions. RESULTS: H2S stabilizes Nrf2 protein and induces
      Nrf2-target genes via an antioxidant-/electrophile-response element. In mouse
      embryonic fibroblasts, the ability of H2S to protect against cell death caused by
      the redox-cycling agent menadione is dependent on Nrf2. Moreover, Nrf2 regulates
      murine genes involved in the production of H2S (Cystathionine-beta-synthase [Cbs]
      and Cystathionine-gamma-lyase [Cse]) and the degradation of H2S (Sulfide:quinone
      reductase-like [yeast] [Sqrdl]). We found that H2S stabilizes Nrf2 through
      inhibition of Keap1, an event that requires covalent modification of amino acids
      C226 and C613 in the substrate adaptor. Upregulation of Nrf2 by H2S partially
      involves the production of H2O2, which inhibits Keap1 by stimulating the
      formation of an intramolecular disulfide bond between C226 and C613. The Keap1
      C226 and C613 residues are also S-sulfhydrated by H2S, and this may entail
      reduction of the C226-C613 disulfide bridge formed by H2O2. INNOVATION:
      Upregulation of Nrf2 by H2S and H2O2 involves inactivation of Keap1 through
      modification of C226 and C613. CONCLUSION: Inhibition of Keap1 by H2S leads to
      Nrf2-mediated induction of cytoprotective genes. Nrf2 controls Cbs, Cse, and
      Sqrdl, suggesting that a feedback loop exists between Nrf2 and H2S.

PMID- 23145495
TI  - Diminished error-related brain activity as a promising endophenotype for
      substance-use disorders: evidence from high-risk offspring.
AB  - One of the core features of individuals with a substance-use disorder (SUD) is
      the reduced ability to successfully process errors and monitor performance, as
      reflected by diminished error-related negativities (ERN). However, whether these
      error-related brain abnormalities are caused by chronic substance use or rather
      predates it remains unclear. The present study elucidated whether hypoactive
      performance monitoring represents an endophenotypic vulnerability marker for SUD
      by using a high-risk paradigm. We assessed the behavioral components of error
      processing, as well as the amplitude of the ERN in the event-related brain
      potential (ERP) during performance of the Eriksen Flanker Task among high-risk
      adolescents of parents with a SUD (HR; n = 28) and normal-risk controls (NR; n =
      40). Results revealed that HR offspring were characterized by a higher prevalence
      of internalizing symptoms and more frequent cannabis use, the latter having a
      significant influence on the ERN. Interestingly, risk group uniquely predicted
      the negativity amplitude in response to error trials above and beyond confounding
      variables. Moreover, we found evidence of smaller ERN amplitudes in (cannabis use
      naive) HR offspring, reflecting impaired early processing of error information
      and suboptimal performance monitoring, whereas no robust group differences were
      found for overall behavioral performance. This effect was independent of an
      overall reduction in brain activity. Taken together, although we cannot rule out
      alternative explanations, the results of our study may provide evidence for the
      idea that diminished error-processing represents a promising endophenotype for
      SUD that may indicate a vulnerability to the disorder. 

PMID- 23145496
TI  - Aetiology and outcome of open and closed globe eye injuries in children.
AB  - BACKGROUND: This paper reports on the aetiology and outcome of childhood open and
      closed globe eye injuries presenting to the Children's Hospital at Westmead,
      Sydney, Australia from January 2000 to December 2008. DESIGN: Hospital-based
      retrospective study. PARTICIPANTS: Two hundred three cases of childhood eye
      injuries identified in a nine-year period, comprising 81 open globe and 122
      closed globe injuries. METHODS: Hospital records were examined for demographic
      data and injuries were classified into open globe and closed globe, based on the
      Ocular Trauma Classification. MAIN OUTCOME MEASURES: Parameters affecting the
      final visual outcome such as type of injury, zone of injury, initial visual
      acuity, wound length (only in open globe injuries) and lens injury were assessed.
      RESULTS: Most of the eye injuries resulted from the child poking itself or being
      poked accidentally (26%), with the home being the most common place of injury. A
      favourable visual outcome was noted with closed globe injuries as compared with
      open globe injuries (P < 0.01). Parameters that indicated a poor visual outcome
      included globe ruptures, zone 3 injuries, poor initial visual acuity, wound
      length >10 mm and lens trauma. Final visual acuity of 6/12 or better was observed
      in 68% of injured eyes. CONCLUSIONS: This study demonstrated improved visual
      outcomes when compared with previous studies. However, many unsalvageable
      childhood eye injuries with little useful vision were evident, and most
      disconcerting is that the majority of childhood eye injuries in this study were
      preventable.

PMID- 23145498
TI  - Melanoma ex blue nevus: two cases resembling large plaque-type blue nevus with
      subcutaneous cellular nodules.
AB  - Large plaque-type blue nevi with subcutaneous cellular nodules are rare tumors
      occurring on the trunk with deep extension into underlying soft tissues. The
      histopathologic appearance consists of deep nodules resembling cellular blue nevi
      with interspersed foci of common blue nevus. Conservative management has been
      recommended, and metastases have not been observed. This report discusses two
      cases with microscopic features of large plaque-type blue nevi with subcutaneous
      cellular nodules in which comparative genomic hybridization showed chromosomal
      aberrations typical of melanoma. In both cases, the nodules showed gains
      involving chromosome 6p and losses involving chromosome 6q, which are among the
      most commonly found aberrations in melanoma. These copy number changes were not
      present in the less cellular surrounding areas that appeared characteristic of
      blue nevus. These cases illustrate that large blue nevi with a deep, multi
      nodular configuration should be interpreted with caution, and that superficial
      biopsies of such lesions can be misleading. Molecular techniques can provide
      valuable insights in these types of difficult melanocytic neoplasms.

PMID- 23145497
TI  - Comparison of hematologic, biochemical, and coagulation parameters in alpha1,3
      galactosyltransferase gene-knockout pigs, wild-type pigs, and four primate
      species.
AB  - BACKGROUND: The increasing availability of genetically engineered pigs is
      steadily improving the results of pig organ and cell transplantation in non-human
      primates (NHPs). Current techniques offer knockout of pig genes and/or knockin of
      human genes. Knowledge of normal values of hematologic, biochemical, coagulation,
      and other parameters in healthy genetically engineered pigs and NHPs is
      important, particularly following pig organ transplantation in NHPs. Furthermore,
      information on parameters in various NHP species may prove important in selecting
      the optimal NHP model for specific studies. METHODS: We have collected
      hematologic, biochemical, and coagulation data on 71 alpha1,3
      galactosyltransferase gene-knockout (GTKO) pigs, 18 GTKO pigs additionally
      transgenic for human CD46 (GTKO.hCD46), four GTKO.hCD46 pigs additionally
      transgenic for human CD55 (GTKO.hCD46.hCD55), and two GTKO.hCD46 pigs
      additionally transgenic for human thrombomodulin (GTKO.hCD46.hTBM). RESULTS: We
      report these data and compare them with similar data from wild-type pigs and the
      three major NHP species commonly used in biomedical research (baboons,
      cynomolgus, and rhesus monkeys) and humans, largely from previously published
      reports. CONCLUSIONS: Genetic modification of the pig (e.g., deletion of the Gal
      antigen and/or the addition of a human transgene) (i) does not result in
      abnormalities in hematologic, biochemical, or coagulation parameters that might
      impact animal welfare, (ii) seems not to alter metabolic function of vital
      organs, although this needs to be confirmed after their xenotransplantation, and
      (iii) possibly (though, by no means certainly) modifies the hematologic,
      biochemical, and coagulation parameters closer to human values. This study may
      provide a good reference for those working with genetically engineered pigs in
      xenotransplantation research and eventually in clinical xenotransplantation.

PMID- 23145500
TI  - Percutaneous cryoablation of renal masses: Washington University experience of
      treating 129 tumours.
AB  - WHAT'S KNOWN ON THE SUBJECT? AND WHAT DOES THE STUDY ADD?: For patients who are
      unfit for extirpative surgery, percutaneous cryoablation (PCA) presents a
      minimally-invasive alternative for the treatment of renal masses. PCA has been
      demonstrated to be safe, with complication rates <10% being reported
      consistently. Studies have suggested that a minimal and insignificant decline in
      renal function can occur after PCA. Finally, among studies with a follow-up >20
      months, treatment success rates range from 75% to 96%. However, longer-term
      oncological and functional results for patients treated with PCA are relatively
      limited. The present study profiles one of the largest reported experiences with
      PCA for renal masses: 129 tumours in 124 patients. Our complication rate was
      comparable to that observed in other reported studies. At a mean follow-up of 30
      months, treatment success was achieved in 87% of tumours, which is in line with
      published PCA success rates. On multivariable analysis, tumour size >3.0 cm was
      found to be significantly associated with treatment failure. A minimal but
      statistically significant renal functional decline was observed, with 20% of
      patients experiencing a progression in National Kidney Foundation-Chronic Kidney
      Disease stage. On multivariable analysis, age >70 years, hilar tumour location
      and postoperative day 1 estimated glomerular filtration rate <60 mL/min/1.73 m(2)
      were found to be significantly associated with renal functional decline. The
      present study confirms that PCA of renal masses represents a safe alternative to
      surgery in patients with substantial medical comorbidities. In the present
      cohort, baseline patient and tumour characteristics probably impact the risk of
      tumour recurrence, as well as renal disease progression, after PCA. OBJECTIVE: To
      evaluate perioperative, oncological and functional outcomes after percutaneous
      cryoablation (PCA) for renal masses based on our single-centre experience.
      PATIENTS AND METHODS: We retrospectively identified 124 patients who underwent
      PCA for 129 renal tumours between March 2005 and June 2011. Patient demographics
      and baseline clinical characteristics, tumour features, perioperative
      information, and postoperative outcomes were recorded. Oncological outcomes were
      defined by radiographic evidence of recurrence on follow-up computed tomography
      or magnetic resonance imaging. Renal disease progression was defined by a change
      in National Kidney Foundation-Chronic Kidney Disease stage. RESULTS: Patients had
      mean (sd) age of 72.6 (10.2) years; mean (sd) tumour size and nephrometry score
      were 2.7 (1.1) cm and 6.5 (1.7), respectively. Our overall complication rate was
      9% (11/124), whereas the major (greater than Clavien II) complication rate was 2%
      (2/124). Significant predictors of renal disease progression following PCA
      included age >= 70 years (odds ratio [OR], 4.31, P = 0.03), hilar tumour location
      (OR, 4.67, P = 0.04), and post operative day 1 estimated glomerular filteration
      rate <=60 mL/min/1.73 m(2) (OR, 7.09, P = 0.02). Our treatment success rate was
      87% (112/129) at a mean (sd) follow-up of 30.2 (18.8) months. Tumour size >=3.0
      cm was significantly associated with PCA failure (hazard ratio, 3.21, P = 0.03).
      CONCLUSION: PCA provides a safe and oncologically effective alternative to
      extirpative surgery for renal masses in patients with significant medical
      comorbidities.

PMID- 23145499
TI  - An active metabolite of oltipraz (M2) increases mitochondrial fuel oxidation and
      inhibits lipogenesis in the liver by dually activating AMPK.
AB  - BACKGROUND AND PURPOSE: Oltipraz, a cancer chemopreventive agent, has an anti
      steatotic effect via liver X receptor-alpha (LXRalpha) inhibition. Here we have
      assessed the biological activity of a major metabolite of oltipraz (M2) against
      liver steatosis and steatohepatitis and the underlying mechanism(s). EXPERIMENTAL
      APPROACH: Blood biochemistry and histopathology were assessed in high-fat diet
      (HFD)-fed mice treated with M2. An in vitroHepG2 cell model was used to study the
      mechanism of action. Immunoblotting, real-time PCR and luciferase reporter assays
      were performed to measure target protein or gene expression levels. KEY RESULTS:
      M2 treatment inhibited HFD-induced steatohepatitis and diminished oxidative
      stress in liver. It increased expression of genes encoding proteins involved in
      mitochondrial fuel oxidation. Mitochondrial DNA content and oxygen consumption
      rate were enhanced. Moreover, M2 treatment repressed activity of LXRalpha and
      induction of its target genes, indicating anti-lipogenic effects. M2 activated
      AMP-activated protein kinase (AMPK). Inhibition of AMPK by over-expression of
      dominant negative AMPK (DN-AMPK) or by Compound C prevented M2 from inducing
      genes for fatty acid oxidation and repressed sterol regulatory element binding
      protein-1c (SREBP-1c) expression. M2 activated liver kinase B1 (LKB1) and
      increased the AMP/ATP ratio. LKB1 knockdown failed to reverse target protein
      modulations or AMPK activation by M2, supporting the proposal that both LKB1 and
      increased AMP/ATP ratio contribute to its anti-steatotic effect. CONCLUSION AND
      IMPLICATIONS: M2 inhibited liver steatosis and steatohepatitis by enhancing
      mitochondrial fuel oxidation and inhibiting lipogenesis. These effects reflected
      activation of AMPK elicited by increases in LKB1 activity and AMP/ATP ratio.

PMID- 23145501
TI  - Large scale synthesis of 2'-amino-LNA thymine and 5-methylcytosine nucleosides.
AB  - Thymine intermediate 17 has been synthesized on a multigram scale (50 g, 70 mmol)
      from starting sugar 1 in 15 steps in an overall yield of 73%, with only 5
      purification steps. The key thymine intermediate 18 was obtained from 17 in a
      single step in 96% yield, whereas the key 5-methylcytosine intermediate 20 was
      obtained from 17 in 2 steps in 58% yield. This highly efficient large scale route
      necessitates only 2 and 3 novel steps to obtain N2'-functionalized thymine and 5
      methylcytosine amino-LNA phosphoramidites from these key intermediates,
      respectively.

PMID- 23145502
TI  - Reactive-layer-assisted deposition mechanism and characterization of titanium
      oxide films.
AB  - The growth mechanism of TiO(2) films and their morphology are reported using the
      reactive-layer-assisted deposition (RLAD) method under ultrahigh vacuum
      conditions. The oxide film formation involves Ti atom deposition on top of
      amorphous solid water (ASW) condensed on a SiO(2)/Si(100) support at 90 K.
      Subsequent annealing leads to the desorption of all nonreacted buffer molecules,
      resulting in the deposition of the titanium oxide film. Employing mass
      spectrometry and using D(2)O as a buffer, we detected the evolution of deuterium
      molecules during titanium atom deposition. A solid state sol-gel-like formation
      mechanism of titanium oxide is proposed on the basis these observations. The
      morphology of the oxide films is characterized by AFM as a rather uniform
      amorphous thin film at room temperature. Upon further annealing above 750 K,
      crystallization of the titanium oxide film has set in, coinciding with a
      dewetting process of the oxide layer, and information obtained from similar
      growth procedure on an amorphous carbon-covered TEM grid. It was shown that these
      films are rather insensitive to the underlying substrate at temperatures below
      500 K.

PMID- 23145503
TI  - Root-soil friction: quantification provides evidence for measurable benefits for
      manipulation of root-tip traits.
AB  - To penetrate soil, a root requires pressure both to expand the cavity it is to
      occupy, sigman , and to overcome root-soil friction, sigmaf . Difficulties in
      estimating these two pressures independently have limited our ability to estimate
      the coefficient of soil-root friction, MUsr . We used a rotated penetrometer
      probe, of similar dimensions to a root, and for the first time entering the soil
      at a similar rate to a root tip, to estimate sigman . Separately we measured root
      penetration resistance (PR) Qr . Root PR was between two to four times sigman .
      We estimated that the coefficient of root-soil friction (MUsr ) was 0.21-0.26,
      based on the geometry of the root tip. This is slightly larger than the 0.05-0.15
      characteristic of boundary lubricants. Scanning electron microscopy showed that
      turgid border cells lined the root channel, supporting our hypothesis that the
      lubricant consisted of mucilage sandwiched between border cells and the surface
      of the root cap and epidermis. This cell-cell lubrication greatly decreased the
      friction that would otherwise be experienced had the surface of the root proper
      slid directly past unlubricated soil particles. Because root-soil friction can be
      a substantial component of root PR, successful manipulation of friction
      represents a promising opportunity for improving plant performance.

PMID- 23145505
TI  - Recessively inherited forms of osteogenesis imperfecta.
AB  - More than 90% of people who have osteogenesis imperfecta (OI) have heterozygous
      mutations in one of the two type I collagen genes, COL1A1 and COL1A2. The effects
      of these changes range from death in the perinatal period to barely increased
      fracture frequency and reflect different types of mutations. Introduction of
      bisphosphonates during the past 20 years has targeted bone fragility by decreased
      resorption. The recent recognition of biallelic mutations in genes that affect
      either collagen assembly and processing or the regulation of osteoblast
      development has raised hopes for therapies that would be specific for single-gene
      disorders and identify cellular targets in individuals with the dominant forms of
      OI. These hopes are yet to be met, but the study of the recessively inherited
      forms of OI has illuminated the details of the collagen processing pathways.

PMID- 23145504
TI  - Singing classes for chronic obstructive pulmonary disease: a randomized
      controlled trial.
AB  - BACKGROUND: There is some evidence that singing lessons may be of benefit to
      patients with chronic obstructive pulmonary disease (COPD). It is not clear how
      much of this benefit is specific to singing and how much relates to the classes
      being a group activity that addresses social isolation. METHODS: Patients were
      randomised to either singing classes or a film club for eight weeks. Response was
      assessed quantitatively through health status questionnaires, measures of
      breathing control, exercise capacity and physical activity and qualitatively,
      through structured interviews with a clinical psychologist. RESULTS: The singing
      group (n=13 mean(SD) FEV1 44.4(14.4)% predicted) and film group (n=11 FEV1
      63.5(25.5)%predicted) did not differ significantly at baseline. There was a
      significant difference between the response of the physical component score of
      the SF-36, favouring the singing group +12.9(19.0) vs -0.25(11.9) (p=0.02), but
      no difference in response of the mental component score of the SF-36, breathing
      control measures, exercise capacity or daily physical activity. In the
      qualitative element, positive effects on physical well-being were reported in the
      singing group but not the film group. CONCLUSION: Singing classes have an impact
      on health status distinct from that achieved simply by taking part in a group
      activity. TRIALS REGISTRATION: Registration Current Controlled Trials -
      ISRCTN17544114.

PMID- 23145506
TI  - Inhibitory effect of opiates on LPS mediated release of TNF and IL-8.
AB  - Most patients with advanced cancer experience severe pain and are often treated
      with opiates. Cancer patients are especially susceptible to opportunistic
      infections due to treatment with immunosuppressive and cytostatic drugs. Since
      opiates have been demonstrated to have immunomodulatory effects, it is of
      clinical importance to evaluate potential differences between commonly used
      opiates with regard to their effect on the immune system. The aim of this study
      was to evaluate the effect of morphine, tramadol, fentanyl and ketobemidone on
      the functioning of the immune system with special reference to TNF and IL-8
      release. Method. U-937 cells were preincubated with different concentrations of
      opioids followed by stimulation with LPS 100 MUg/ml for three hours. The effect
      of opioids on the levels of cytokine mRNA was studied using RT-PCR. Erk and Akt
      phosphorylation was also measured by Western blot. Results. All opioids with the
      exception of fentanyl were capable of inhibiting TNF release from U-937 cells.
      Morphine had no effect on IL-8 release but the effect of other opiates was almost
      the same as the effect on TNF. All opioids with the exception of fentanyl were
      capable of inhibiting production of mRNA for TNF and IL-8. The observed effects
      of opiates were not always reversible by naloxone, suggesting that the effects
      might be mediated by other receptors or through a non-receptor mediated direct
      effect. Although preliminary evidence suggests the involvement of Erk and Akt
      pathways, further studies are needed to unravel the intracellular pathways
      involved in mediating the effects of opiates. Our data suggests that the order of
      potency with regard to inhibition of cytokine release is as follows: tramadol >
      ketobemidone > morphine > fentanyl. Conclusion. Further studies are needed to
      understand the clinical implications of the observed immunosuppressive effects of
      tramadol and ketobemidone and to improve opioid treatment strategies in patients
      with cancer.

PMID- 23145507
TI  - Time trends in chemotherapy (administration and costs) and relative survival in
      stage III colon cancer patients - a large population-based study from 1990 to
      2008.
AB  - BACKGROUND: Use of adjuvant chemotherapy for stage III colon cancer has increased
      since several trials have shown the beneficial effect on survival. In this
      population-based study we show time trends in the administration and costs of
      chemotherapy and relative survival of patients with stage III colon cancer.
      METHODS: All patients surgically treated for adenocarcinoma of the colon stage
      III between 1990 and 2008 in The Netherlands were included. Relative survival
      (using period analyses) and Relative Excess Risks of death (RER) were calculated.
      The costs of chemotherapy were estimated. RESULTS: A total of 24 111 colon cancer
      patients with stage III were included in the cohort. The administration (from
      9.5% in 1990 to 61.8% in 2008; p < 0.001) and costs of chemotherapy (from ?38 467
      in 1990 to ?3 876 150 in 2008) increased during the study period. Multivariable
      relative survival improved for patients receiving adjuvant chemotherapy (RER
      0.93; 95% CI 0.92-0.94; p < 0.001). In contrast, relative survival remained
      stable for patients, younger than 80 years, who did not receive chemotherapy (RER
      1.00; 95% CI 1.00-1.01; p = 0.3). Patients aged 80 years and older without
      chemotherapy, relative survival increased during the study period (RER 0.98; 95%
      CI 0.97-0.99; p < 0.001). CONCLUSIONS: The administration, the costs of
      chemotherapy and the survival of patients with stage III colon cancer increased
      over time. Whereas the costs and administration of chemotherapy increased
      extensively, relative survival increased to a lesser extent. For patients treated
      with adjuvant chemotherapy relative survival increased equally in all age groups.

PMID- 23145508
TI  - ACE and AGTR1 polymorphisms in elite rhythmic gymnastics.
AB  - In the angiotensin-converting enzyme (ACE) gene, Alu deletion, in intron 16, is
      associated with higher concentrations of ACE serum activity and this may be
      associated with elite sprint and power performance. The Alu insertion is
      associated with lower ACE levels and this could lead to endurance performance.
      Moreover, recent studies have identified a single-nucleotide polymorphism of the
      angiotensin type 1 receptor gene AGTR1, which seems to be related to ACE
      activity. The aim of this study was to examine the involvement of the ACE and the
      AGTR1 gene polymorphisms in 28 Italian elite rhythmic gymnasts (age range 21 +/-
      7.6 years), and compare them to 23 middle level rhythmic gymnasts (age range 17
      +/- 10.9 years). The ACE D allele was significantly more frequent in elite
      athletes than in the control population (chi(2)=4.07, p=0.04). Comparisons
      between the middle level and elite athletes revealed significant differences
      (p<0.0001) for the ACE DD genotype (OR=6.48, 95% confidence interval=1.48-28.34),
      which was more frequent in elite athletes. There were no significant differences
      in the AGTR1 A/C genotype or allele distributions between the middle level and
      elite athletes. In conclusion, the ACE D allele genotype could be a contributing
      factor to high-performance rhythmic gymnastics that should be considered in
      athlete development and could help to identify which skills should be trained for
      talent promotion.

PMID- 23145509
TI  - Photophysical properties and singlet oxygen generation of three sets of
      halogenated corroles.
AB  - The luminescence, excited-state absorption, and singlet oxygen generation
      measurements were performed on three kinds of halogenated corroles: monohydroxyl
      halogenated corroles (Corrole-F, Corrole-Cl, Corrole-I), peripherally fluorine
      substituted corroles (F0, F5, F10, F15), and gallium complexes (F10-Ga, F15-Ga).
      The fluorescence intensities progressively decrease whereas the triplet quantum
      yields, oxygen quenching rates, and singlet oxygen quantum yields increase with
      the increasing of the monohydroxyl halogen atomic weight. Replacing hydrogen
      atoms of meso-phenyl groups with fluorine atoms induces the blue-shifts of the
      emission spectra, higher triplet quantum yield, and smaller oxygen quenching
      rates. Of all peripherally fluorine-substituted corroles, F10 exhibited the
      highest singlet oxygen quantum yield. In comparison with the free base corroles,
      both gallium corrole complexes display much stronger fluorescence with the large
      blue-shifts of emission peaks and slightly higher triplet quantum yields but
      smaller oxygen quenching rates and singlet oxygen quantum yields. The reasons for
      the different photophysical behaviors of these corroles are discussed.

PMID- 23145510
TI  - Toxoplasma gondii in waterfowl: the first detection of this parasite in Anas
      crecca and Anas clypeata from Italy.
AB  - Understanding the spread of Toxoplasma gondii in waterfowl is of interest for
      elucidating the potential involvement of these birds in maintaining the parasitic
      life cycle because birds are exposed to these parasites. Sera from 103 adult,
      free-range game birds, representing 13 different species living in the Italian
      wetlands, were examined using modified agglutination tests for antibodies
      specific to T. gondii . In seropositive birds, the brain and heart were
      homogenized and DNA was extracted to perform nested polymerase chain reaction
      (nPCR) and genotyping. Out of the 103 serum samples, 9 (8.7%) were scored as
      positive with titers ranging from 1/20 to 1/160. The seropositive animals
      corresponded to 4 of the species: Anas platyrhynchos (mallard; 2/17), Anas
      clypeata (northern shoveller; 2/11), Anas crecca (common teal; 3/41), and
      Gallinago gallinago (common snipe; 2/8). Parasite DNA was detected in 3 out of 9
      brain samples, while the PCR results from the heart specimens were negative in
      all of the birds. The occurrence of non-clonal types of T. gondii was suggested
      in all cases. In conclusion, we describe the first documented detection of DNA of
      T. gondii in tissues from the northern shoveller and common teal, thereby
      extending the range of intermediate hosts for this parasite.

PMID- 23145511
TI  - Editorial: Your leadership style--how are you working to achieve a preferred
      future?

PMID- 23145512
TI  - The role of patient safety culture in the causation of unintended events in
      hospitals.
AB  - AIMS AND OBJECTIVES: To examine whether the relationship between specialty and
      patient safety is mediated by safety culture. BACKGROUND: Research has shown that
      patient safety in hospitals varies by specialty. The safety culture among
      healthcare professionals in hospital units is believed to influence safety
      performance. If there is a mediation effect of safety culture in the relationship
      between specialty and safety, then safety culture could explain why units vary in
      performance. DESIGN: Cross-sectional observational study in 28 units of 20
      hospitals in the Netherlands. Units were of three specialties: emergency
      medicine, surgery and internal medicine. METHODS: Safety culture was measured
      with the Dutch version of the Hospital Survey on Patient Safety Culture with 11
      culture dimensions (n = 542; response 56%). Safety outcomes were types of
      unintended events (six types). Unintended events were collected through staff
      reporting (n = 1885 events). Data were examined using multilevel regression
      analysis. RESULTS: The overall safety culture in the units did not mediate the
      relationship between specialty and the safety outcomes (event types), but three
      of the 11 dimensions showed significant mediation on one or more event types: non
      punitive response to error, hospital management support and willingness to
      report. CONCLUSIONS: Only a few safety culture dimensions mediated the
      relationship between specialty and some of the outcomes, with 'willingness to
      report' as the most important mediating factor. Our study did not give strong
      evidence that specialties differ in performance because of their safety cultures.
      More research into the causes of variation in patient safety between hospital
      units is needed. RELEVANCE TO CLINICAL PRACTICE: Our study could not give support
      for the claim that safety culture is a key factor affecting patient safety.

PMID- 23145513
TI  - Evaluation of an individual sleep intervention programme in people undergoing
      peritoneal dialysis treatment.
AB  - AIMS AND OBJECTIVES: This study aimed to evaluate effects of a non
      pharmacological intervention on sleep, activity and fatigue in patients receiving
      peritoneal dialysis by the use of both actigraphy registration and self-assessed
      questionnaires. BACKGROUND: Insomnia is estimated to affect up to 60% of haemo-
      and peritoneal dialysis patients. It is associated with two common uremic
      symptoms, pruritus and restless legs syndrome. To our knowledge, no interventions
      have been evaluated by actigraphy. DESIGN: A prospective multiple baseline single
      case experimental design. METHODS: Two women and seven men with sleep problems,
      48-77 years, treated with PD participated in a 17-week study from January 2009 to
      February 2011. Two interventions were separately implemented. First, a pressure
      relieving mattress and second, a four week individual sleep hygiene and sleep
      scheduling intervention. The two interventions were evaluated both objectively by
      actigraphy and subjectively by questionnaires. RESULTS: A total of 315 sleep-wake
      cycles from nine individuals were evaluated. Three patients improved clinically
      significantly in five or more of the nine outcomes, i.e. sleep onset latency,
      nocturnal sleep duration, numbers and duration of napping, movement and
      fragmentation index, number of steps, metabolic equivalent unit, sleep efficiency
      and fatigue. The other six patients also showed improvements but to a lesser
      degree. Physical activity advice was the intervention that yielded most sleep
      improvements. CONCLUSIONS: This study illuminates the need for regular assessment
      of sleep and tiredness. It also demonstrates how a non-pharmacological treatment
      and self-management can be applied with renal supportive care to improve sleep
      quality. RELEVANCE TO CLINICAL PRACTICE: This study is a clinical example of a
      non-pharmacological intervention with supportive care and self-management. This
      model can improve health and reduce the pharmacological burden because hypnotics
      can be replaced by sleep hygiene self-care activities.

PMID- 23145514
TI  - What is missed in self-immolated patients' care? A grounded theory study.
AB  - AIMS AND OBJECTIVES: To explore rehabilitation care process in patients who
      commit self-immolation. BACKGROUND: Self-immolation is not only a type of burn
      injury, but it is also a suicidal method. It is placed in burn injury category
      that requires long-term rehabilitation and treatment measures. As a suicidal
      method, among all forms of suicidal attempts, it is the most dramatic, violent
      and often difficult one to understand. Unfortunately, there are few reported
      studies investigating experiences and perceptions of nurses about burn care and
      with qualitative study about the patients' experiences and perceptions. DESIGN:
      On the basis of the research question, the grounded theory method was used.
      METHODS: Considering ethical codes of Belmont and Helsinki statements, purposive
      sampling was used to select the participants. The patients were deliberately
      selected, based on the research needs. They were self-immolated patients being
      referred to Talaghani hospital of Ilam (western Iran) or discharged previously
      (time of interview and observation ranged from immediately later the burn till 5
      years after), in Ilam, where self-immolation rate is very high. The main methods
      for data collection were deep, open ended, semi-structured interviews, dairies
      and observations. The interviews were audio taped in Persian, and verbatim
      transcriptions were made. By doing so, semantic meaning is preserved, and
      misinterpretation of data due to translation into English is minimised. Data
      analysis was conducted using the Strauss and Corbin method. RESULTS: Five main
      categories were emerged: situation of crisis unprofessional care, prolongation
      and formidability of the journey, self-immolation as paralyse, and attempt for
      self-management. Finally, by constant, comparison of collected data and emerged
      categories, central variable entitled unintegrated care emerged as the main
      problem of self-immolated patients' care. CONCLUSION: The study comes to the
      conclusion that we need to focus on specific considerations to provide integrated
      care for the burned patients as it is a decisive component of care that is
      missed. RELEVANCE TO CLINICAL PRACTICE: Although self-immolation requires long
      term treatment and social, emotional rehabilitation, such a rehabilitation care
      process is not clear.

PMID- 23145515
TI  - Self-transcendence and nurse-patient interaction in cognitively intact nursing
      home patients.
AB  - AIMS AND OBJECTIVES: The aim of this study was to test whether nurse-patient
      interaction affects cognitively intact nursing home patients' interpersonal and
      intrapersonal self-transcendence, as well as testing the psychometric properties
      of the Nurse-Patient Interaction Scale (NPIS). BACKGROUND: Self-transcendence is
      considered a spiritual developmental process of maturity in adulthood, and a
      vital resource of well-being at the end of life. The concept of self
      transcendence has previously been explored in various populations, yet the nurse
      patient interactions' potential influence on self-transcendence in nursing home
      patients has not been published previously. DESIGN AND METHODS: A cross-sectional
      design employing the Self-Transcendence Scale and the NPIS was adopted. A sample
      of 202 cognitively well-functioning nursing home patients in Norway was selected.
      The statistical analyses were carried out using lisrel 8.8 and structural
      equation modelling. RESULTS: Structural equation modelling-analysis indicates
      statistical significant effect of nurse-patient interaction on the patients' self
      transcendence. Direct influence on the intrapersonal and indirect influence on
      the interpersonal self-transcendence aspects was disclosed. CONCLUSION: Nurse
      patient interaction significantly affected both interpersonal and intrapersonal
      self-transcendence among cognitively intact nursing home patients. Hence,
      facilitating caring interventions can be significantly beneficial to older
      patients' self-transcendence and thereby well-being, both emotional and physical.
      RELEVANCE TO CLINICAL PRACTICE: Caring behaviour signifies the vital and ultimate
      qualitative nursing behaviour, which promotes self-transcendence and thereby well
      being. These findings are important for clinical nursing that intends to increase
      patients' well-being.

PMID- 23145516
TI  - A literature review: Graduate nurses' preparedness for recognising and responding
      to the deteriorating patient.
AB  - AIMS AND OBJECTIVES: To explore the research literature that provided data on
      factors that influence new graduate nurse's preparedness for recognition and
      response to patient deterioration in the acute care setting. BACKGROUND: Nurses
      have a significant role in recognising subtle signs of patient deterioration and
      responding appropriately to prevent adverse events and improve patient outcomes.
      This pivotal position has often fallen to the new graduate who must be prepared
      to make high-consequence decisions in relation to a suspected decline in their
      patient's condition. DESIGN AND METHODS: An integrative review was undertaken. A
      comprehensive literature search was conducted using online databases, reference
      lists of key articles and expert advice. Multiple keyword combinations were used.
      All relevant studies were subsequently appraised for rigour and quality.
      Seventeen primary research studies drawn from novice and experienced registered
      nurse experiences emerged as relevant to the review. RESULTS: Thematic analysis
      of the studies provided six major themes related to the aim of the review.
      Emergent themes were as follows: clinical staff support, lack of nurse
      experience, overwhelming workload, holistic patient assessment, past experiences
      and lack of available resources. CONCLUSIONS: This review highlighted the
      importance of positive staff support and subsequent confidence building.
      Graduates then felt able to present effective assessments and less fearful of
      reprimand when escalating an intervention call. The need for further research to
      investigate graduate nurses' experiences of recognising and responding to the
      deteriorating patient emerged. RELEVANCE TO CLINICAL PRACTICE: Realistic
      workloads and access to supportive experienced staff would allow graduates time
      to focus on grouping clinical information to understand the 'total picture' of
      the patient. Results indicated undergraduate and hospital in-service education
      programmes needed to offer the opportunity to practice reasoning. Complex
      clinical situations involving patient deterioration through simulation and
      clinical placement opportunities appeared most useful.

PMID- 23145517
TI  - The effectiveness of simulation activities on the cognitive abilities of
      undergraduate third-year nursing students: a randomised control trial.
AB  - AIMS AND OBJECTIVES: To provide evidence on the effectiveness of simulation
      activities on the clinical decision-making abilities of undergraduate nursing
      students. Based on previous research, it was hypothesised that the higher the
      cognitive score, the greater the ability a nursing student would have to make
      informed valid decisions in their clinical practice. BACKGROUND: Globally,
      simulation is being espoused as an education method that increases the competence
      of health professionals. At present, there is very little evidence to support
      current investment in time and resources. METHODS: Following ethical approval,
      fifty-eight third-year undergraduate nursing students were randomised in a
      pretest-post-test group-parallel controlled trial. The learning environment
      preferences (LEP) inventory was used to test cognitive abilities in order to
      refute the null hypothesis that activities in computer-based simulated learning
      environments have a negative effect on cognitive abilities when compared with
      activities in skills laboratory simulated learning environments. RESULTS: There
      was no significant difference in cognitive development following two cycles of
      simulation activities. Therefore, it is reasonable to assume that two simulation
      tasks, either computer-based or laboratory-based, have no effect on an
      undergraduate student's ability to make clinical decisions in practice. However,
      there was a significant finding for non-English first-language students, which
      requires further investigation. CONCLUSIONS: More longitudinal studies that
      quantify the education effects of simulation on the cognitive, affective and
      psychomotor attributes of health science students and professionals from both
      English-speaking and non-English-speaking backgrounds are urgently required. It
      is also recommended that to achieve increased participant numbers and prevent non
      participation owing to absenteeism, further studies need to be imbedded directly
      into curricula. RELEVANCE TO CLINICAL PRACTICE: This investigation confirms the
      effect of simulation activities on real-life clinical practice, and the
      comparative learning benefits with traditional clinical practice and university
      education remain unknown.

PMID- 23145518
TI  - Emotional intelligence as a predictor of academic performance in first-year
      accelerated graduate entry nursing students.
AB  - AIMS AND OBJECTIVES: To examine the association between trait emotional
      intelligence and learning strategies and their influence on academic performance
      among first-year accelerated nursing students. DESIGN: The study used a
      prospective survey design. METHODS: A sample size of 81 students (100% response
      rate) who undertook the accelerated nursing course at a large university in
      Sydney participated in the study. Emotional intelligence was measured using the
      adapted version of the 144-item Trait Emotional Intelligence Questionnaire. Four
      subscales of the Motivated Strategies for Learning Questionnaire were used to
      measure extrinsic goal motivation, peer learning, help seeking and critical
      thinking among the students. The grade point average score obtained at the end of
      six months was used to measure academic achievement. RESULTS: The results
      demonstrated a statistically significant correlation between emotional
      intelligence scores and critical thinking (r = 0.41; p < 0.001), help seeking (r
      = 0.33; p < 0.003) and peer learning (r = 0.32; p < 0.004) but not with extrinsic
      goal orientation (r = -0.05; p < 0.677). Emotional intelligence emerged as a
      significant predictor of academic achievement (beta = 0.25; p = 0.023).
      CONCLUSION: In addition to their learning styles, higher levels of awareness and
      understanding of their own emotions have a positive impact on students' academic
      achievement. Higher emotional intelligence may lead students to pursue their
      interests more vigorously and think more expansively about subjects of interest,
      which could be an explanatory factor for higher academic performance in this
      group of nursing students. RELEVANCE TO CLINICAL PRACTICE: The concepts of
      emotional intelligence are central to clinical practice as nurses need to know
      how to deal with their own emotions as well as provide emotional support to
      patients and their families. It is therefore essential that these skills are
      developed among student nurses to enhance the quality of their clinical practice.

PMID- 23145519
TI  - Clinical comparison of patients with refractory angina with and without the
      nursing diagnosis of activity intolerance.

PMID- 23145520
TI  - Introduction of Paediatric Yorkhill Malnutrition Score--challenges and impact on
      nursing practice.

PMID- 23145521
TI  - Health-promoting lifestyle of a group of Iranian medical, nursing and allied
      health students.

PMID- 23145522
TI  - Patient participation in quality improvement: managers' opinions of patients as
      resources.

PMID- 23145523
TI  - Commentary on Van der Doef M, Mbazzi FM and Verhoeven C (2011) Job conditions,
      satisfaction, somatic complaints and burnout. Journal of Clinical Nursing 21,
      1763-1775.

PMID- 23145524
TI  - Can a new ultra-long-acting insulin analogue improve patient care? Investigating
      the potential role of insulin degludec.
AB  - The basal-bolus concept of delivering insulin to diabetic patients makes
      physiological sense, as it mimics normal insulin release in people without
      diabetes. In line with this concept, a major effort put forth by insulin
      manufacturers has been to develop the ideal exogenous basal insulin product. The
      perfect basal insulin product would be injected into subcutaneous tissue without
      causing irritation, release insulin continuously at a constant rate for at least
      24 hours, be stable, not contribute to weight gain, have a low risk of allergic
      reactions and, very importantly, minimize the risk of hypoglycaemia. While the
      perfect insulin has not yet been discovered, advancements are still being made.
      Insulin degludec is an ultra-long-acting basal insulin analogue that possesses a
      flat, stable glucose-lowering effect in patients with type 1 or type 2 diabetes
      mellitus. Insulin degludec achieves these pharmacokinetic properties by forming
      soluble multihexamers upon subcutaneous injection, resulting in the formation of
      a depot in the subcutaneous tissue that is slowly released and absorbed into
      circulation. Insulin degludec has been associated with slightly less weight gain
      and fewer nocturnal hypoglycaemic episodes when compared with insulin glargine in
      some, but not all, clinical studies. This article briefly reviews current
      evidence for the use of insulin degludec in patients with type 1 or type 2
      diabetes mellitus and discusses the potential impact of this new basal insulin on
      clinical practice.

PMID- 23145525
TI  - The chloroplast ATP synthase features the characteristic redox regulation
      machinery.
AB  - SIGNIFICANCE: Regulation of the activity of the chloroplast ATP synthase is
      largely accomplished by the chloroplast thioredoxin system, the main redox
      regulation system in chloroplasts, which is directly coupled to the
      photosynthetic reaction. We review the current understanding of the redox
      regulation system of the chloroplast ATP synthase. RECENT ADVANCES: The
      thioredoxin-targeted portion of the ATP synthase consists of two cysteines
      located on the central axis subunit gamma. The redox state of these two cysteines
      is under the influence of chloroplast thioredoxin, which directly controls
      rotation during catalysis by inducing a conformational change in this subunit.
      The molecular mechanism of redox regulation of the chloroplast ATP synthase has
      recently been determined. CRITICAL ISSUES: Regulation of the activity of the
      chloroplast ATP synthase is critical in driving efficiency into the ATP synthesis
      reaction in chloroplasts. FUTURE DIRECTIONS: The molecular architecture of the
      chloroplast ATP synthase, which confers redox regulatory properties requires
      further investigation, in light of the molecular structure of the enzyme complex
      as well as the physiological significance of the regulation system.

PMID- 23145526
TI  - Eosinophilic pulmonary granulomatosis in a young dog with prolonged remission
      after treatment.
AB  - A two-year-old Jack Russell terrier was presented for evaluation of chronic cough
      and exercise intolerance. Previous treatment with antibiotics and glucocorticoids
      had only partially ameliorated the clinical signs. During investigation,
      hypoxaemia, peripheral eosinophilia and an eosinophilic bronchoalveolar lavage
      fluid were noted. Thoracic radiographs revealed two ovoid clearly delineated soft
      tissue opacities, one in the caudal segment of the left cranial lung lobe
      (diameter 26 mm) and the other in the right cranial lung lobe (diameter 20 mm).
      These findings were verified by computed tomography, which identified an
      additional smaller lesion (diameter 16 mm) dorsally in the right caudal lobe.
      Ultrasound-guided fine-needle aspiration samples confirmed the diagnosis of
      eosinophilic pulmonary granulomatosis and treatment with prednisolone and
      azathioprine was initiated. Within 1 month, granulomas were no longer detectable
      radiographically. All medication was discontinued after 7 months and currently,
      after 2.5 years, the dog remains free of clinical signs. To the authors'
      knowledge this is the first case report to describe prolonged remission from
      idiopathic canine eosinophilic pulmonary granulomatosis.

PMID- 23145528
TI  - Prospective longitudinal study of corneal collagen cross-linking in progressive
      keratoconus.
AB  - BACKGROUND: Collagen cross-linking has been reported to be effective in treating
      progressive keratoconus, and this study aims to evaluate the long-term efficacy
      of this procedure. DESIGN: Prospective longitudinal interventional study of
      patients with progressive keratoconus who underwent cross-linking in a tertiary
      referral hospital. PARTICIPANTS: Thirty-five patients (51 eyes) who underwent
      cross-linking with a mean follow-up of 14.38 +/- 9.36 months (range 6-48) were
      compared with a control group of 25 fellow eyes that did not undergo the
      procedure. METHODS: Cross-linking was performed using 0.1% riboflavin (in 20%
      dextran T500) and ultraviolet A irradiation (370 nm, 3 mW/cm(2) , 30 min). MAIN
      OUTCOME MEASURES: Maximum keratometry in dioptres, logMAR best spectacle
      corrected visual acuity, cylindrical power, manifest refraction spherical
      equivalent and central corneal thickness. RESULTS: Analysis of the treated group
      demonstrated a significant flattening of maximum keratometry by 0.96 +/- 2.33
      dioptres (P = 0.005) and a significant improvement in visual acuity by 0.05 +/-
      0.13 logMAR (P = 0.04). In the control group, maximum keratometry increased
      significantly by 0.43 +/- 0.85 dioptres (P = 0.05), and visual acuity decreased
      by mean 0.05 +/- 0.14 (P = 0.2). No statistical differences were noted regarding
      cylindrical power, spherical equivalent or corneal thickness in both groups.
      CONCLUSIONS: Results indicate that corneal collagen cross-linking using
      riboflavin and ultraviolet A is effective as a therapeutic option in cases of
      progressive keratoconus by reducing the corneal curvature and by improving the
      visual acuity in these patients.

PMID- 23145527
TI  - Opioid sensitivity in mice selectively bred to consume or not consume
      methamphetamine.
AB  - There has been little investigation of genetic factors and associated mechanisms
      that influence risk for development of methamphetamine (MA) dependence.
      Selectively bred mouse lines that exhibit high (MAHDR) or low (MALDR) levels of
      MA intake in a two-bottle choice MA drinking (MADR) procedure provide a genetic
      tool for this purpose. These lines were used to determine whether opioid
      sensitivity and MA intake are genetically associated, because opioid-mediated
      pathways influence some effects of MA. Sensitivity to the analgesic effects of
      the MU-opioid receptor (MOP-r) agonist fentanyl (0.05, 0.1, 0.2, 0.4 mg/kg) was
      examined using two acute thermal tests (hot plate and tail flick) and one chronic
      pain test (magnesium sulfate abdominal constriction). Locomotor stimulant
      responses to fentanyl (0.05, 0.1, 0.2, 0.4 mg/kg) and morphine (10, 20, 30 mg/kg)
      were also examined. In addition, MADR was measured in the progenitor strains
      [(C57BL/6J (B6), DBA/2J (D2)] of the F2 population from which the selected lines
      were generated. The MADR lines did not differ in sensitivity to the analgesic
      effects of fentanyl; however, MALDR mice exhibited greater locomotor activation
      than MAHDR mice to both fentanyl and morphine. D2 mice consumed more MA than B6
      mice. The line differences for MA consumption and morphine activation
      recapitulated B6 and D2 strain differences for these two traits, but not strain
      differences previously found for opioid analgesic responses. These results
      support a negative genetic correlation between MA consumption and sensitivity to
      the stimulant effects of opioids and suggest the involvement of MOP-r regulated
      systems in MA intake. 

PMID- 23145529
TI  - Occupational and recreational noise exposure from indoor arena hockey games.
AB  - Occupational and recreational noise exposures were evaluated at two sporting
      arenas hosting collegiate hockey games (Venue 1) and semi-professional hockey
      (Venue 2). A total of 54 personal noise dosimetry samples were taken over the
      course of seven home hockey games: 15 workers and 9 fans at Venue 1, and 19
      workers and 11 fans at Venue 2. None of the sampled workers were overexposed to
      noise based on Occupational Safety and Health Administration criteria. However,
      40% and 57% of workers at Venue 1 and 33% and 91% of fans at Venue 2 were
      overexposed based on ACGIH noise exposure criteria. Noise exposures for fans were
      significantly different between venues, but worker noise exposures between venues
      were not significantly different. In addition, extensive area noise monitoring
      was conducted at each venue to further characterize the stadium noise on a
      location-by-location basis. Mean equivalent sound pressure levels ranged from 81
      to 96 dBA at Venue 1 and from 85 to 97 dBA at Venue 2. Mean noise peak levels
      ranged from 105 to 124 dBA at Venue 1, and from 110 to 117 dBA at Venue 2. These
      data reflect the potential for overexposure at indoor hockey events and are
      useful in characterizing occupational noise exposure of indoor arena support
      staff and may also provide a foundation for future noise control research in
      indoor sports arenas.

PMID- 23145530
TI  - Cell population-specific expression analysis of human cerebellum.
AB  - BACKGROUND: Interpreting gene expression profiles obtained from heterogeneous
      samples can be difficult because bulk gene expression measures are not resolved
      to individual cell populations. We have recently devised Population-Specific
      Expression Analysis (PSEA), a statistical method that identifies individual cell
      types expressing genes of interest and achieves quantitative estimates of cell
      type-specific expression levels. This procedure makes use of marker gene
      expression and circumvents the need for additional experimental information like
      tissue composition. RESULTS: To systematically assess the performance of
      statistical deconvolution, we applied PSEA to gene expression profiles from
      cerebellum tissue samples and compared with parallel, experimental separation
      methods. Owing to the particular histological organization of the cerebellum, we
      could obtain cellular expression data from in situ hybridization and laser
      capture microdissection experiments and successfully validated computational
      predictions made with PSEA. Upon statistical deconvolution of whole tissue
      samples, we identified a set of transcripts showing age-related expression
      changes in the astrocyte population. CONCLUSIONS: PSEA can predict cell-type
      specific expression levels from tissues homogenates on a genome-wide scale. It
      thus represents a computational alternative to experimental separation methods
      and allowed us to identify age-related expression changes in the astrocytes of
      the cerebellum. These molecular changes might underlie important physiological
      modifications previously observed in the aging brain.

PMID- 23145531
TI  - CD99 expression in Merkel cell carcinoma: a case series with an unusual
      paranuclear dot-like staining pattern.
AB  - BACKGROUND: Merkel cell carcinoma (MCC) is a rare neuroendocrine cancer of the
      skin. The utility of CD99 (MIC-2) in the diagnosis of MCC has been previously
      studied, with reported rates of expression ranging from 13 to 55%. When
      specified, a membranous or cytoplasmic staining pattern was considered
      significant. Recent studies of CD99 have identified a paranuclear dot-like
      expression pattern in certain non-neuroendocrine pancreatic and colonic lesions.
      We recently noted paranuclear dot-like staining in several cases of MCC,
      including cases lacking cytokeratin 20 (CK20) expression. METHODS: Fourteen cases
      of MCC were stained with CK20 and CD99 antibody, and the pattern and intensity of
      staining were recorded. Seven cases of pulmonary small cell carcinoma (PSCC) and
      one case of primitive neuroectodermal tumor (PNET) were used for comparison.
      RESULTS: All 14 cases of MCC showed at least focal CD99 staining, with both
      membranous and paranuclear dot-like staining patterns identified. CK20 staining
      was present in 12/14 cases, with the characteristic dot-like pattern identified.
      Four of seven cases of PSCC showed CD99 staining, with two showing a finely
      granular dot-like staining pattern. CONCLUSIONS: We report an unusual pattern of
      paranuclear dot-like expression of CD99 in 14 cases of MCC, two of which did not
      express CK20. This previously unrecognized expression pattern may be of use in
      differentiating MCC from other cutaneous malignancies, especially when CK20
      expression is limited or absent.

PMID- 23145532
TI  - Impact of the introduction of a robotic training programme on prostate cancer
      stage migration at a single tertiary referral centre.
AB  - OBJECTIVE: To evaluate the trend in robot-assisted radical prostatectomy (RARP)
      and open retropubic radical prostatectomy (RRP) use over time and to compare
      preoperative and pathological characteristics of patients treated with RARP or
      RRP at a single centre. PATIENTS AND METHODS: Between 2006 and 2010, 2511
      consecutive patients treated with RP, with or without pelvic lymph node
      dissection (PLND), for prostate cancer (PCa) at a single tertiary care centre
      were analysed. Baseline patient characteristics and PCa risk distribution were
      compared according to treatment type (RRP vs RARP) in the overall population, as
      well as in three surgeons' initial 50 RARP and three surgeons' initial 50 RRP
      cases (n = 300). We used a chi-squared trend test to evaluate the differences in
      treatment type administration over time according to PCa characteristics.
      Logistic regression analyses focused on the prediction of PLND and adjuvant
      radiotherapy (RT) use. RESULTS: Overall, 1873 (74.6%) and 638 (25.4%) patients
      underwent RRP and RARP, respectively. Men treated with RARP were younger (mean
      age: 62 vs 65 years), less obese (mean BMI: 24.8 vs 26.4 kg/m(2) ), healthier
      (Charlson comorbidity index = 0: 68.7 vs 53.3%) and more likely to harbour
      clinical low-risk PCa (51 vs 30%) than their RRP counterparts (all P < 0.001).
      Similar findings were observed in sub-analyses focusing on six surgeons' 50
      initial patients (all P <= 0.02). A significant increase in the rate of patients
      with low-risk PCa treated with RARP vs RRP was reported over time (5 vs 95% and
      66 vs 34% in 2006 and 2010, respectively). Conversely, 76% of patients with high
      risk PCa were still treated with RRP in 2010. Patients treated with RARP were
      less likely to receive PLND at RP and adjuvant RT (all P <= 0.01), even after
      adjusting for clinical and PCa characteristics. CONCLUSIONS: The introduction of
      a robotic training programme at a high volume centre led to significant patient
      selection in terms of clinical and PCa characteristics. When both RRP and RARP
      facilities are available within the same centre, patients with the most
      favourable clinical and cancer profile are selected to undergo RARP. Use of RARP
      negatively influenced the rates and the extent of PLND as well as the use of
      adjuvant RT after surgery. Thus, baseline patient selection, surgical and
      treatment biases make any comparisons of RARP with RRP problematic.

PMID- 23145533
TI  - Gas-phase reactions of microsolvated fluoride ions: an investigation of different
      solvents.
AB  - The gas-phase reactions of F(-)(DMSO), F(-)(CH(3)CN), and F(-)(C(6)H(6)) with t
      butyl halides were investigated. Reaction rate constants, kinetic isotope
      effects, and product ion branching ratios were measured using the flowing
      afterglow selected ion flow tube technique (FA-SIFT). Additionally, the structure
      of F(-)(DMSO) was investigated both computationally and experimentally, and two
      stable isomers were identified. The reactions generally proceed by elimination
      mechanisms; however, the reaction of F(-)(C(6)H(6)) with t-butyl chloride occurs
      by a switching mechanism. These reactions are compared to previous studies of
      microsolvated reactions of t-butyl halides where the solvent molecules were
      polar, protic molecules.

PMID- 23145534
TI  - UV photoactivated room temperature CVD of aluminum on functionalized self
      assembled monolayers adsorbed on Au.
AB  - We have investigated the selective photoactivated room temperature chemical vapor
      deposition (CVD) of aluminum (Al) on functionalized self-assembled monolayers
      adsorbed on Au. The CVD precursor employed is trimethyl aluminum (TMA). Using a
      deuterium arc lamp we demonstrate that the rate of the Al film growth is
      approximately twice that observed for nonphotoactivated Al chemical vapor
      deposition (CVD) using TMA. At the wavelengths employed, the photolysis of TMA
      leads to the dissociation of the TMA dimer to its monomer followed by successive
      release of methyl groups to form (CH(3))(3-x)Al. The photogenerated (CH(3))(3
      x)Al species react with -OH- and -COOH-terminated SAMs but not -CH(3)-terminated
      SAMs. Using these reactions we demonstrate that aluminum can be selectively
      deposited on -CH(3)/-COOH-patterned SAMs. The possible reaction mechanisms
      involved in the Al film growth are discussed. These results indicate that
      photoactivated CVD (laser CVD) processes are suitable for the deposition of
      stable films of metals and other materials on organic films.

PMID- 23145535
TI  - Is it useful to ask why plants emit isoprene?

PMID- 23145536
TI  - Mine or yours? Development of sharing in toddlers in relation to ownership
      understanding.
AB  - To examine early developments in other-oriented resource sharing, fifty-one 18-
      and 24-month-old children were administered 6 tasks with toys or food that could
      be shared with an adult playmate who had none. On each task the playmate
      communicated her desire for the items in a series of progressively more explicit
      cues. Twenty-four-month-olds shared frequently and spontaneously. Eighteen-month
      olds shared when given multiple opportunities and when the partner provided
      enough communicative support. Younger children engaged in self-focused and
      hypothesis-testing behavior in lieu of sharing more often than did older
      children. Ownership understanding, separately assessed, was positively associated
      with sharing and negatively associated with non-sharing behavior, independent of
      age and language ability.

PMID- 23145538
TI  - Biased processing of sleep-related stimuli in children of parents with insomnia.
AB  - Disorder-specific cognitive biases have been observed in children whose parents
      suffer from psychological disorders. Despite those same biases being observed in
      individuals with insomnia, they have yet to be explored as an index of
      vulnerability in children of parents with insomnia. It was hypothesized that
      potentially vulnerable children would demonstrate cognitive biases to sleep
      related cues, relative to controls. Following a "tired-state induction," a sleep
      related Emotional Stroop was completed by 2 groups: 38 children of parents with
      insomnia and 51 controls. Children also reported their observations about the
      content of the Stroop words. Results showed an attention bias in children whose
      parents have insomnia, but no interpretive bias. The results are discussed in
      terms of a predispositional vulnerability to insomnia.

PMID- 23145539
TI  - Effect of indium segregation on the surface versus bulk chemistry for indium
      doped TiO2.
AB  - This work reports the effect of indium segregation on the surface versus bulk
      composition of indium (In)-doped TiO(2). The studies are performed using proton
      induced X-ray emission (PIXE), secondary-ion mass spectrometry (SIMS), X-ray
      photoelectron spectroscopy (XPS), and Rutherford backscattering spectroscopy
      (RBS). The results of XPS analysis indicate that annealing of In-doped TiO(2)
      containing 0.3 atom % In at 1273 K in the gas phase of controlled oxygen activity
      [p(O(2)) = 75 kPa and 10 Pa] results in a surface enrichment of 2.95 and 2.61
      atom % In, respectively. The obtained segregation data are considered in terms of
      the transport of indium ions from its titanium sites in the bulk phase to the
      surface where these ions are incorporated into interstitial sites. The effect of
      oxygen activity on the segregation-induced surface enrichment is considered in
      terms of the formation of a low-dimensional surface structure and a sublayer,
      which are charged negatively. The latter is formed as a result of strong
      interactions between titanium vacancies and interstitial indium ions, leading to
      the formation of defect complexes. The data obtained in this work may be used for
      engineering of TiO(2)-based semiconductors with enhanced performance in solar
      energy conversion.

PMID- 23145537
TI  - Oral zinc supplementation restores high molecular weight seminal zinc binding
      protein to normal value in Iraqi infertile men.
AB  - BACKGROUND: Zinc in human seminal plasma is divided into three types of ligands
      which are high (HMW), intermediate (IMW), and low molecular weight ligands (LMW).
      The present study was aimed to study the effect of Zn supplementation on the
      quantitative and qualitative characteristics of semen along with Zinc Binding
      Protein levels in the seminal plasma in asthenozoospermic patients. METHODS:
      Semen samples were obtained from 37 fertile and 37 asthenozoospermic infertile
      men with matched age. The subfertile group was treated with zinc sulfate, every
      participant took two capsules per day for three months (each one 220 mg). Semen
      samples were obtained (before and after zinc sulfate supplementation). After
      liquefaction seminal fluid at room temperature, routine semen analyses were
      performed. For determination of the amount of zinc binding proteins, the gel
      filtration of seminal plasma on Sephadex G-75 was performed. All the fractions
      were investigated for protein and for zinc concentration by atomic absorption
      spectrophotometry. Evaluation of chromatograms was made directly from the zinc
      concentration in each fraction. RESULTS: A significant high molecular weight zinc
      binding ligands percentage (HMW-Zn %) was observed in seminal plasma of fertile
      males compared with subfertile males. However, seminal low molecular weight
      ligands (LMW-Zn) have opposite behavior. The mean value of semen volume,
      progressive sperm motility percentage and total normal sperm count were increased
      after zinc sulfate supplementation. CONCLUSIONS: Zinc supplementation restores
      HMW-Zn% in seminal plasma of asthenozoospermic subjects to normal value. Zinc
      supplementation elevates LMW-Zn% in seminal plasma of asthenozoospermic subjects
      to more than normal value. TRIAL REGISTRATION: ClinicalTrials.gov identifier
      NCT01612403.

PMID- 23145540
TI  - Intramolecular electronic couplings in class II/III organic mixed-valence systems
      of bis(1,4-dimethoxybenzene).
AB  - The intramolecular electronic couplings in organic mixed-valence systems [D
      (ph)(n)-D](*+) (D = 2,5-dimethoxy-4-methylphenyl, n = 0, 1, and 2) are calculated
      by dominantly using density functional theory to investigate their dependence of
      functionals. Since these systems have the property that the charge is from
      localization to delocalization, the optimized structures are sensitive to the
      functionals. The geometric optimizations show that CAM-B3LYP and omegaB97X-D
      functionals are good choices for delocalized systems and LC-omegaPBE and M06HF
      are suitable for the systems from charge almost localization to localization. The
      calculations of electronic couplings demonstrate that the pure functional
      generally underestimates the electronic couplings whereas the pure HF
      overestimates them. Furthermore, the electronic couplings from the conventional
      generalized Mulliken-Hush method are very sensitive to the HF component in
      functionals, which makes it a challenge to accurately estimate the values. A new
      reduced two-state method is thus proposed to overcome the deficiency, and the
      obtained electronic couplings are less sensitive to the omega value in LC-omega
      PBE functional and they are also consistent with the experimental data.

PMID- 23145541
TI  - Absence of an association between lumican promoter variants and high myopia in
      the Korean population.
AB  - PURPOSE: To determine the association of single nucleotide polymorphisms (SNPs)
      in the promoter region of the lumican (LUM) gene with high myopic Korean
      patients. METHODS: Genomic DNA samples were obtained from 128 unrelated Korean
      patients with high myopia who had refractive errors <= -9.25 and axial lengths >=
      26.5 mm in both eyes, and 235 control subjects. We investigated two promoter SNPs
      of the LUM gene. RESULTS: For the rs3759222, the C/C genotype was less prevalent
      in the high myopia group compared to the control group (46.1% vs. 53.2%);
      however, there was no statistical significance (p = 0.068, OR = 0.754, 95% CI:
      0.491-1.159). The "C" allele frequency in the high myopia group (68.0%) was
      slightly lower than the control group (72.6%), but this difference was not
      statistically significant (p = 0.061, OR = 0.810, 95% CI:0.582-1.126). For the
      rs3759223, the genotype frequencies of T/T, T/C, and C/C were 67.2%, 26.6%, and
      6.2%, respectively, in the high myopia group and 64.7%, 30.6%, and 4.7 %,
      respectively, in the control group. The allele frequency of T was 80.5% in the
      high myopia group and 80.0% in the control group (p = 0.077, OR = 1.03, 95% CI:
      0.703-1.508). There were no significant differences in the distribution of
      genotype and allele frequencies for the two promoter SNPs tested. CONCLUSIONS:
      The current study did not support an association between the promoter SNPs of the
      LUM gene with high myopia in the Korean population.

PMID- 23145543
TI  - Graphene-passivated nickel as an oxidation-resistant electrode for spintronics.
AB  - We report on graphene-passivated ferromagnetic electrodes (GPFE) for spin
      devices. GPFE are shown to act as spin-polarized oxidation-resistant electrodes.
      The direct coating of nickel with few layer graphene through a readily scalable
      chemical vapor deposition (CVD) process allows the preservation of an unoxidized
      nickel surface upon air exposure. Fabrication and measurement of complete
      reference tunneling spin valve structures demonstrate that the GPFE is maintained
      as a spin polarizer and also that the presence of the graphene coating leads to a
      specific sign reversal of the magneto-resistance. Hence, this work highlights a
      novel oxidation-resistant spin source which further unlocks low cost wet
      chemistry processes for spintronics devices.

PMID- 23145542
TI  - Loss of genetic variability in social spiders: genetic and phylogenetic
      consequences of population subdivision and inbreeding.
AB  - The consequences of population subdivision and inbreeding have been studied in
      many organisms, particularly in plants. However, most studies focus on the short
      term consequences, such as inbreeding depression. To investigate the consequences
      of both population fragmentation and inbreeding for genetic variability in the
      longer term, we here make use of a natural inbreeding experiment in spiders,
      where sociality and accompanying population subdivision and inbreeding have
      evolved repeatedly. We use mitochondrial and nuclear data to infer phylogenetic
      relationships among 170 individuals of Anelosimus spiders representing 23
      species. We then compare relative mitochondrial and nuclear genetic variability
      of the inbred social species and their outbred relatives. We focus on four
      independently derived social species and four subsocial species, including two
      outbred-inbred sister species pairs. We find that social species have 50% reduced
      mitochondrial sequence divergence. As inbreeding is not expected to reduce
      genetic variability in the maternally inherited mitochondrial genome, this
      suggests the loss of variation due to strong population subdivision, founder
      effects, small effective population sizes (colonies as individuals) and lineage
      turnover. Social species have < 10% of the nuclear genetic variability of the
      outbred species, also suggesting the loss of genetic variability through founder
      effects and/or inbreeding. Inbred sociality hence may result in reduction in
      variability through various processes. Sociality in most Anelosimus species
      probably arose relatively recently (0.1-2 mya), with even the oldest social
      lineages having failed to diversify. This is consistent with the hypothesis that
      inbred spider sociality represents an evolutionary dead end. Heterosis underlies
      a species potential to respond to environmental change and/or disease. Inbreeding
      and loss of genetic variability may thus limit diversification in social
      Anelosimus lineages and similarly pose a threat to many wild populations subject
      to habitat fragmentation or reduced population sizes.

PMID- 23145544
TI  - Speech assessment of Chinese-English bilingual children: accent versus
      developmental level.
AB  - The study aimed to evaluate the phonological profiles of Chinese-English
      bilingual children in primary grades relative to those of English monolinguals,
      and to compare these profiles with speech-language pathologists' (SLPs') ratings
      of children's speech in terms of accent or developmental level. Participants were
      29 Chinese-English bilinguals and 25 English-monolingual children. Speech samples
      were collected using the Goldman-Fristoe Test of Articulation-2, either a
      Cantonese or Mandarin phonology test, and three sentences in a delayed repetition
      task. In addition, 10 SLPs rated each of the randomized sentences on either an
      accent or developmental level scale. Bilingual children with identified accents
      had significantly lower standard scores than monolingual children on the GFTA-2,
      but on the Chinese phonological assessments the same children showed age-expected
      speech. The differences in the bilingual children's scores on phonology tests in
      English vs Chinese highlight the need for phonological assessment in both
      languages. The SLP listener results further suggest that perceptual judgement may
      be a useful complement in phonological assessment of bilingual children but not a
      replacement for more formal testing.

PMID- 23145546
TI  - Experimental measure of retinal impact force resulting from intraocular foreign
      body dropped onto retina through media of differing viscosity.
AB  - BACKGROUND: To evaluate and compare the perfluorocarbon liquid, silicone oil, and
      viscoelastic against standard saline, in their ability to dampen the impact force
      of a foreign body, dropped within the eye. In an experimental surgical model in
      where cohesive and adhesive forces of the substances are not enough to float
      heavy-than-water foreign bodies. METHODS: A model of ophthalmic surgery was
      constructed. A BB pellet was dropped from 24 mm onto a force transducer through
      four different fluids: balanced salt solution, perfluoro-n-octane, viscoelastic,
      and silicone oil. The impact energy (force) for each case was measured and
      recorded by the force transducer. The mean force of impact for each fluid was
      compared using the Student t-test. RESULTS: Silicone oil resulted in the lowest
      force of impact. Both silicone oil and viscoelastic dampened the impact an order
      of magnitude more than perfluoro-n-octane and balanced salt solution.
      CONCLUSIONS: Silicone oil and viscoelastic cushioned the force from a dropped BB.
      They may be useful adjuncts to prevent iatrogenic retinal injury during
      vitrectomy for intraocular foreign body removal.

PMID- 23145549
TI  - Chronic disease prevention and the politics of scale: lessons from Canadian
      health reform.
AB  - The authors examine the politics of health-promotion dissemination in health
      policy using provincial cases from the Canadian Heart Health Initiative (CHHI)
      Dissemination Phase, a nationwide chronic disease prevention initiative that took
      place between 1994 and 2005. Drawing on an analysis of health policy documents
      and key informant interviews from three provincial CHHI projects, the authors
      highlight the challenges to incorporate health-promotion strategies oriented
      toward collective approaches to health within variably "individual" oriented
      policy climates during a time of health reform. In doing this, the authors
      uncover a "politics of scale" where researchers developed very different
      strategies to advance chronic disease prevention within a contested political
      terrain. What emerged were strategies unique to provincial context. Understanding
      the politics of scale within health policy development provides insight into how
      health-promotion strategies should be shaped to achieve maximum effect.

PMID- 23145548
TI  - A comparison of two experimental design approaches in applying conjoint analysis
      in patient-centered outcomes research: a randomized trial.
AB  - BACKGROUND: While the application of conjoint analysis and discrete-choice
      experiments in health are now widely accepted, a healthy debate exists around
      competing approaches to experimental design. There remains, however, a paucity of
      experimental evidence comparing competing design approaches and their impact on
      the application of these methods in patient-centered outcomes research.
      OBJECTIVES: Our objectives were to directly compare the choice-model parameters
      and predictions of an orthogonal and a D-efficient experimental design using a
      randomized trial (i.e., an experiment on experiments) within an application of
      conjoint analysis studying patient-centered outcomes among outpatients diagnosed
      with schizophrenia in Germany. METHODS: Outpatients diagnosed with schizophrenia
      were surveyed and randomized to receive choice tasks developed using either an
      orthogonal or a D-efficient experimental design. The choice tasks elicited
      judgments from the respondents as to which of two patient profiles (varying
      across seven outcomes and process attributes) was preferable from their own
      perspective. The results from the two survey designs were analyzed using the
      multinomial logit model, and the resulting parameter estimates and their robust
      standard errors were compared across the two arms of the study (i.e., the
      orthogonal and D-efficient designs). The predictive performances of the two
      resulting models were also compared by computing their percentage of survey
      responses classified correctly, and the potential for variation in scale between
      the two designs of the experiments was tested statistically and explored
      graphically. RESULTS: The results of the two models were statistically identical.
      No difference was found using an overall chi-squared test of equality for the
      seven parameters (p = 0.69) or via uncorrected pairwise comparisons of the
      parameter estimates (p-values ranged from 0.30 to 0.98). The D-efficient design
      resulted in directionally smaller standard errors for six of the seven
      parameters, of which only two were statistically significant, and no differences
      were found in the observed D-efficiencies of their standard errors (p = 0.62).
      The D-efficient design resulted in poorer predictive performance, but this was
      not significant (p = 0.73); there was some evidence that the parameters of the D
      efficient design were biased marginally towards the null. While no statistical
      difference in scale was detected between the two designs (p = 0.74), the D
      efficient design had a higher relative scale (1.06). This could be observed when
      the parameters were explored graphically, as the D-efficient parameters were
      lower. CONCLUSIONS: Our results indicate that orthogonal and D-efficient
      experimental designs have produced results that are statistically equivalent.
      This said, we have identified several qualitative findings that speak to the
      potential differences in these results that may have been statistically
      identified in a larger sample. While more comparative studies focused on the
      statistical efficiency of competing design strategies are needed, a more pressing
      research problem is to document the impact the experimental design has on
      respondent efficiency.

PMID- 23145550
TI  - Quality of life and life skill baseline measures of urban adolescents with
      disabilities.
AB  - Many gaps exist in the understanding of how adolescents with disabilities
      successfully transition to adulthood and the services contributing to this
      success. This study attempts to fill one gap by establishing quality of life
      baseline measures for low-income urban adolescents. We compared baseline data for
      a representative sample of adolescents with disabilities in the District of
      Columbia to national norms using three instruments-the Pediatric Quality of Life
      Inventory 4.0, the Ansell-Casey Life Skills Assessment, and the Career Maturity
      Inventory-Attitude Scale. The sample for this study was primarily African
      American and had a higher level of disability as measured by receipt of
      Supplemental Security Income (SSI). The baseline scores of the adolescents in DC
      may be lower than the normed scores of their peers with disabilities in the U.S.
      because of socioeconomic and racial inequities and because the population has to
      contend with greater levels of disabilities.

PMID- 23145551
TI  - Effects of a cost-sharing policy on disenrollment from a state health insurance
      program.
AB  - Subsidized public health insurance programs face financial difficulties and are
      increasingly implementing policies to pass on greater costs to low-income
      enrollees. Results of a stratified, random sample of 1,153 enrollees and
      disenrollees of a state program after introduction of increased cost sharing
      revealed three main reasons for disenrollment, which varied by enrollee income:
      finding other coverage, becoming financially ineligible, or dropping coverage as
      too expensive. Seventeen percent of disenrollees cited cost sharing as a reason
      for disenrollment. Persons who disenrolled were more likely to be younger adults,
      male, and have fewer children. Persons who disenrolled reported greater
      subsequent out-of-pocket costs, more difficulty providing coverage for children,
      and less access to care than persons who stayed enrolled. Most enrollees stayed
      enrolled despite the cost sharing increases, and persons who did disenroll left
      for a variety of reasons, only one of which was cost. Implications for state
      health insurance policies are discussed.

PMID- 23145552
TI  - Integrated services plus drug treatment as a system alternative to crime control
      and parole.
AB  - Integrated services have the potential to facilitate recovery in drug offenders
      as well as reduce criminal recidivism. This is significant given that prison
      overcrowding has led many drug offenders to be released from custody into society
      via the "reentry movement." Offenders incarcerated for many years often return to
      society with medical, mental health, behavioral, and drug abuse issues. These
      issues have been found in similar populations, including those with severe mental
      illness and the homeless, for which integrated services has shown to have a
      significant impact on improving functioning. Thus the argument of this article is
      that because integrated services have shown to be effective with somewhat similar
      populations, integrated services can be effective in treating paroled drug
      offenders. These benefits are expected to be to a greater degree than that
      achieved by current system policy regarding paroled drug offenders being
      supervised by parole officers rather than case managers facilitating integrated
      services.

PMID- 23145553
TI  - The moderating effect of school type on the relationship between school-based
      health centers and the learning environment.
AB  - School-Based Health Centers (SBHCs) have improved access to primary and
      preventive health care for underserved children and youth by bringing
      comprehensive health services into the schools while addressing critical health
      problems that make it difficult for students to learn. Despite the findings on
      the positive effects of SBHCs on health outcomes, the literature investigating
      the relationship between SBHCs and the learning environment is scant. This study
      utilizes a quasi experimental study to investigate the moderating effects of
      school type on the relationship between school based health centers and the
      learning environment. Findings indicate that SBHCs in middle and elementary
      schools are associated with greater levels of school engagement and satisfaction
      with the learning environment than those in high schools.

PMID- 23145555
TI  - Effective reduction of nonspecific binding by surface engineering of quantum dots
      with bovine serum albumin for cell-targeted imaging.
AB  - Quantum dots (QDs) have been widely used as fluorescent probes in cell-targeted
      imaging. However, nonspecific binding to cellular membranes has been a major
      challenge. In this study, a new approach is developed for effective reduction of
      nonspecific binding by bovine serum albumin (BSA)-coated QDs in cell targeting.
      The experimental results show efficient transfer of hydrophobic QDs from organic
      to aqueous phase in the presence of BSA aqueous solution under ultrasonication.
      This ultrasonication-based approach is facile, rapid, and efficient.
      Stabilization of QDs is mainly achieved by multiple mercapto groups in BSA
      macromolecules as multidentate ligands and partially by hydrophobic interaction
      between BSA and pending fatty ligands on QDs. The water solubility of QDs is
      enhanced by the surface amino and carboxyl groups, which also provide reaction
      sites for conjugation of targeting ligands. The BSA-coated QDs, with an
      overwhelming majority of hydrodynamic diameter size of ca. 18 nm, are colloidally
      stable under both acidic and basic conditions and found to exhibit strong
      fluorescent intensities. The nonspecific cellular binding is effectively reduced
      by BSA-coated QDs, compared with the mercaptopropionic acid (MPA)-coated CdTe
      QDs. BSA-coated QDs are further functionalized with cyclic Arg-Gly-Asp (cRGD)
      peptide. The cell assays indicate their high target-selectivity in integrin
      alpha(v)beta(3)-expressed cell imaging.

PMID- 23145556
TI  - Volatile isoprenoid emissions from plastid to planet.
AB  - Approximately 1-2% of net primary production by land plants is re-emitted to the
      atmosphere as isoprene and monoterpenes. These emissions play major roles in
      atmospheric chemistry and air pollution-climate interactions. Phenomenological
      models have been developed to predict their emission rates, but limited
      understanding of the function and regulation of these emissions has led to large
      uncertainties in model projections of air quality and greenhouse gas
      concentrations. We synthesize recent advances in diverse fields, from cell
      physiology to atmospheric remote sensing, and use this information to propose a
      simple conceptual model of volatile isoprenoid emission based on regulation of
      metabolism in the chloroplast. This may provide a robust foundation for scaling
      up emissions from the cellular to the global scale.

PMID- 23145557
TI  - Breaking the cycle: how light, CO2 and O2 affect plant respiration.

PMID- 23145558
TI  - Electrospun azido-PCL nanofibers for enhanced surface functionalization by click
      chemistry.
AB  - This paper reports highly surface functionalized and "clickable" alpha,omega
      azido-poly(epsilon-caprolactone) fibers (f-PCL-N(3)), obtained by classical
      electrospinning setup. Azide-functionalized PCL was obtained from a commercially
      available alpha,omega-poly(epsilon-caprolactone)-diol, PCL(2), and electrospun
      with a nonderivative high-molecular-weight PCL. Successful chemical modifications
      of PCL(2) were confirmed by NMR, FTIR and MALDI-TOF mass spectroscopy. The high
      content of surface azides, as a response to the high electric field applied, was
      characterized using a colorimetric assay. In addition, azide reduction to amines
      revealed a nondestructive route for highly amine-functionalized fibers.
      Fluorescence labeling of f-PCL-N(3) fibers with FITC-alkyne fluorophore proved
      that the azide groups are mainly surface-localized as well as highly available
      for click-chemistry coupling.

PMID- 23145559
TI  - Reliability and validity of self-assessment of mouth opening: a validation study.
AB  - BACKGROUND: The objective of this study was to evaluate the reproducibility and
      validity of patients' mouth opening measurements in a research setting. METHODS:
      Firstly, 68 patients made repeated self-measurements of mouth opening using a
      cardboard scale (Therabite Range of Motion Scale - TRMS). Secondly, 80 patients
      enrolled in a clinical trial on morbidity after lower third molar surgery, made
      daily assessments during the postoperative week. Patients' measurements were then
      compared to gold-standard clinicians' measurements. RESULTS: Reliability of
      patients' measurements was excellent with an intraclass correlation coefficient
      of 0.92. The patient's measurements correlated well with the gold-standard
      clinician's measurements, both for the first 68 patients (Pearson's rho ranging
      from 0.86 to 0.90, p < 0.0001) as well as for the 80 patients enrolled in the
      clinical trial (rho = 0.82, p < 0.0001 at day 2, rho = 0.83, p < 0.0001 at final
      visit). CONCLUSIONS: TRMS can be used by patients to produce reproducible and
      valid mouth opening measurements.

PMID- 23145560
TI  - Chronic ketamine exposure induces permanent impairment of brain functions in
      adolescent cynomolgus monkeys.
AB  - Ketamine, a non-competitive N-methyl-D-aspartic acid receptor antagonist, has
      emerged as an increasingly popular drug among young drug abusers worldwide.
      Available evidence suggests that ketamine produces acute impairments of working,
      episodic and semantic memory along with psychotogenic and dissociative effects
      when a single dose is given to healthy volunteers. However, understanding of the
      possible chronic effects of ketamine on behavior, cognitive anomalies and
      neurochemical homeostasis is still incomplete. Although previous human studies
      demonstrate that ketamine could impair a range of cognitive skills, investigation
      using non-human models would permit more precise exploration of the neurochemical
      mechanisms which may underlie the detrimental effects. The current study examined
      the abnormalities in behavior (move, walk, jump and climb) and apoptosis of the
      prefrontal cortex using terminal deoxynucleotidyl transferase-mediated
      biotinylated dUTP nick end labeling (TUNEL) and apoptotic markers, including Bax,
      Bcl-2 and caspase-3 in adolescent male cynomolgus monkeys (Macaca fascicularis)
      after 1 or 6 months of sub-anesthetic ketamine administration (1 mg/kg, i.v.).
      Results showed that ketamine decreased locomotor activity and increased cell
      death in the prefrontal cortex of monkeys with 6 months of ketamine treatment
      when compared with the control monkeys. Such decreases were not found in the 1
      month ketamine-treated group. Our study suggested that ketamine administration of
      recreational dose in monkeys might produce permanent and irreversible deficits in
      brain functions due to neurotoxic effects, involving the activation of apoptotic
      pathways in the prefrontal cortex. 

PMID- 23145561
TI  - Industrialized research in the BJCP: a neo-Luddite view.

PMID- 23145564
TI  - The effect of age on the haptic horizontal-vertical curvature illusion with
      raised-line shapes.
AB  - In the present study, we investigated the effect of age in the haptic horizontal
      vertical curvature illusion from adolescence to old age. Blindfolded participants
      explored raised-line convex curves with one finger and two fingers (Experiment
      1). They judged the size of the curves (horizontal/vertical), using two sliding
      rulers. The results suggest that young and older haptic explorers overestimated
      the vertical. Adolescents did not show the haptic illusion. In Experiment 2,
      adolescents performed the task visually showing a stronger horizontal-vertical
      illusion. The findings suggest that the illusion develops later in touch than in
      vision. The theoretical implications of the results are discussed.

PMID- 23145563
TI  - Genomic consequences of transitions from cross- to self-fertilization on the
      efficacy of selection in three independently derived selfing plants.
AB  - BACKGROUND: Transitions from cross- to self-fertilization are associated with
      increased genetic drift rendering weakly selected mutations effectively neutral.
      The effect of drift is predicted to reduce selective constraints on amino acid
      sequences of proteins and relax biased codon usage. We investigated patterns of
      nucleotide variation to assess the effect of inbreeding on the accumulation of
      deleterious mutations in three independently evolved selfing plants. Using high
      throughput sequencing, we assembled the floral transcriptomes of four individuals
      of Eichhornia (Pontederiaceae); these included one outcrosser and two
      independently derived selfers of E. paniculata, and E. paradoxa, a selfing
      outgroup. The dataset included ~8000 loci totalling ~3.5 Mb of coding DNA.
      RESULTS: Tests of selection were consistent with purifying selection constraining
      evolution of the transcriptome. However, we found an elevation in the proportion
      of non-synonymous sites that were potentially deleterious in the E. paniculata
      selfers relative to the outcrosser. Measurements of codon usage in high versus
      low expression genes demonstrated reduced bias in both E. paniculata selfers.
      CONCLUSIONS: Our findings are consistent with a small reduction in the efficacy
      of selection on protein sequences associated with transitions to selfing, and
      reduced selection in selfers on synonymous changes that influence codon usage.

PMID- 23145565
TI  - Emotional modulation of the ability to inhibit a prepotent response during
      childhood.
AB  - The present study examined the bottom-up influence of emotional context on
      response inhibition, an issue that remains largely unstudied in children. Thus,
      62 participants, aged from 6 to 13 years old, were assessed with three stop
      signal tasks: one with circles, one with neutral faces, and one with emotional
      faces (happy and sad). Results showed that emotional context altered response
      inhibition ability in childhood. However, no interaction between age and
      emotional influence on response inhibition was found. Positive emotions were
      recognized faster than negative emotions, but the valence did not have a
      significant influence on response inhibition abilities.

PMID- 23145566
TI  - Cognitive and behavioral outcomes in individuals with a history of acute
      disseminated encephalomyelitis (ADEM).
AB  - We describe cognitive and behavioral outcomes in 12 males and 7 females diagnosed
      with acute disseminated encephalomyelitis (ADEM) in childhood. Age at assessment
      ranged from 6 to 23 years and all participants were at least 2 years post-ADEM
      presentation (mean 5.4 years). Performance was compared with 18 control subjects.
      Three of 19 ADEM patients met criteria for cognitive impairment, defined as
      performance falling <=1.5 SD on at least three tests. Age at ADEM-onset was not
      associated with outcome. Despite the transient nature of the illness and absence
      of persistent physical disability, cognitive sequelae occur in some individuals
      following childhood ADEM.

PMID- 23145567
TI  - Basic multisensory functions can be acquired after congenital visual pattern
      deprivation in humans.
AB  - People treated for bilateral congenital cataracts offer a model to study the
      influence of visual deprivation in early infancy on visual and multisensory
      development. We investigated cross-modal integration capabilities in cataract
      patients using a simple detection task that provided redundant information to two
      different senses. In both patients and controls, redundancy gains were consistent
      with coactivation models, indicating an integrated processing of modality
      specific information. This finding is in contrast with recent studies showing
      impaired higher-level multisensory interactions in cataract patients. The present
      results suggest that basic cross-modal integrative processes for simple short
      stimuli do not depend on visual and/or crossmodal input since birth.

PMID- 23145568
TI  - A critical look at the relationship between impulsivity and decision-making in
      adolescents: are they related or separate factors?
AB  - This study examined the relations between impulsivity and decision-making as
      assessed by the Iowa Gambling Task (IGT). A total of 73 nonclinical adolescents
      were administered self-report measures for trait impulsivity and the Wisconsin
      Card Sorting Test (WCST) to assess cognitive impulsivity. We found significant
      correlations between trait impulsivity and WCST performance among adolescents
      exhibiting poor performance on the IGT, and no such correlations for those
      adolescents performing well on the IGT. We recommend that researchers should
      assess performance on the IGT at the individual level in terms of learning.

PMID- 23145570
TI  - Efficacy of using harmless Bacillus endospores to estimate the inactivation of
      Cryptosporidium parvum oocysts in water.
AB  - The need to use complex in vitro cell culture, expensive equipment, and highly
      trained technicians that are available only to specialist laboratories has
      significantly limited studies assessing the potential of pulsed UV light (PUV) to
      inactivate the waterborne parasite Cryptosporidium parvum in drinking water. This
      constitutes the first study to report on the use of different non-pathogenic
      Bacillus endospores as potential surrogate organisms to indicate the PUV
      inactivation performance of a C. parvum oocyst suspended in water. Findings
      showed that PUV effectively inactivated approximately 5 log10 CFU/ml Bacillus
      megaterium and Bacillus pumilus endospores suspended in water at a UV dose of
      9.72 MUJ/cm(2) that also inactivated statistically similar levels of C. parvum
      oocysts (P < 0.05), as determined by combined in vitro HCT-8 cell culture and
      quantitative PCR. Specifically, this study demonstrated that B. megaterium
      exhibited greater or similar PUV-inactivation kinetic data compared to that of
      similarly treated C. parvum over the UV dose range 6.4 to 12.9 MUJ/cm(2).
      Therefore, the former may be used as an indicator organism for safely
      investigating the PUV-inactivation performance of this chlorine-resistant,
      waterborne parasite at the waste-water treatment plant level. Findings presented
      will impact positively on future water quality studies and on public health.

PMID- 23145571
TI  - Effect of water on the carbon dioxide absorption by 1-alkyl-3-methylimidazolium
      acetate ionic liquids.
AB  - The absorption of carbon dioxide by the pure ionic liquids 1-ethyl-3
      methylimidazolium acetate ([C(1)C(2)Im][OAc]) and 1-butyl-3-methylimidazolium
      acetate ([C(1)C(4)Im][OAc]) was studied experimentally from 303 to 343 K. As
      expected, the mole fraction of absorbed carbon dioxide is high (0.16 at 303 K and
      5.5 kPa and 0.19 at 303 and 9.6 KPa for [C(1)C(2)Im][OAc] and [C(1)C(4)Im][OAc],
      respectively), does not obey Henry's law, and is compatible with the
      chemisorption of the gas by the liquid. Evidence of a chemical reaction between
      the gas and the liquid was found both by NMR and by molecular simulation. In the
      presence of water, the properties of the liquid absorber significantly change,
      especially the viscosity that decreases by as much as 25% (to 78 mPa s) and 30%
      (to 262 mPa s) in the presence of 0.2 mol fraction of water for [C(1)C(2)Im][OAc]
      and [C(1)C(2)Im][OAc] at 303 K, respectively. The absorption of carbon dioxide
      decreases when the water concentration increases: a decrease of 83% in CO(2)
      absorption is found for [C(1)C(4)Im][OAc] with 0.6 mol fraction of water at 303
      K. It is proved in this work, by combining experimental data with molecular
      simulation, that the presence of water not only renders the chemical reaction
      between the gas and the ionic liquid less favorable but also lowers the
      (physical) solubility of the gas as it competes by the same solvation sites of
      the ionic liquid. The lowering of the viscosity of the liquid absorbent largely
      compensates these apparent drawbacks and the mixtures of [C(1)C(2)Im][OAc] and
      [C(1)C(2)Im][OAc] with water seem promising to be used for carbon dioxide
      capture.

PMID- 23145572
TI  - CLINICAL STUDY OF FLAP DESIGN TO INCREASE THE KERATINIZED GINGIVA AROUND
      IMPLANTS. 4-YEAR FOLLOW-UP.
AB  - Abstract   Purpose: Since the presence of keratinized gingiva is so important for
      peri-implant outcome, the aim of this study is to describe a partial thickness
      flap design to increase the amount of keratinized peri-implant tissue as well as
      its thickness.Materials and Methods: A total of 131 implants were placed: 103
      implants (78.63%) in the mandible and 28 implants (21.37%) in the maxilla, in 85
      patients. Before implant placement in edentulous ridge the residual keratinized
      mucosa usually was measured with a periodontal probe in a buccal-palatal
      direction. A palatal or lingual incision was made in order to raise a partial
      thickness flap with the residual keratinized tissue. After implant placement the
      flap was apically repositioned and secured with loose periosteal sutures.
      Keratinized tissue levels were calculated at baseline, at 6-month, and every year
      follow-up. Measurements were reported for each implant diameter.Results: At 4
      year follow-up, implant survival rate of 87.79% was reported. Peri-implant
      keratinized mucosa confirmed clinical gain in all cases; mean levels at 1-year
      and 4-year follow-up were respectively 7.26 +/- 2.01 mm and 7.37 +/- 2.12 mm. The
      levels remained stable over time.Conclusions: This flap design allows to
      immediately correct the adaptation of the keratinized tissue around the implant,
      increasing the thickness and amount of the keratinized tissue.

PMID- 23145569
TI  - Gene expression in the human brain: the current state of the study of specificity
      and spatiotemporal dynamics.
AB  - Gene expression is one of the main molecular processes regulating the
      differentiation, development, and functioning of cells and tissues. In this
      review a handful of relevant terms and concepts are introduced and the most
      common techniques used in studies of gene expression/expression profiling (also
      referred to as studies of the transcriptome or transcriptomics) are described.
      The main foci of this review are the advancements in studies of the transcriptome
      in the human brain, the transcriptome's variability across different brain
      structures, and the systematic changes that occur through different developmental
      stages across the life span in general and childhood in particular. Finally, the
      question of how the accumulating data on the spatial and temporal dynamics of the
      transcriptome may shed light on the molecular mechanisms of the typical and
      atypical development of the central nervous system is addressed.

PMID- 23145573
TI  - Hexagonal platelet-like magnetite as a biosignature of thermophilic iron-reducing
      bacteria and its applications to the exploration of the modern deep, hot
      biosphere and the emergence of iron-reducing bacteria in early precambrian
      oceans.
AB  - Dissimilatory iron-reducing bacteria are able to enzymatically reduce ferric iron
      and couple to the oxidation of organic carbon. This mechanism induces the
      mineralization of fine magnetite crystals characterized by a wide distribution in
      size and irregular morphologies that are indistinguishable from authigenic
      magnetite. Thermoanaerobacter are thermophilic iron-reducing bacteria that
      predominantly inhabit terrestrial hot springs or deep crusts and have the
      capacity to transform amorphous ferric iron into magnetite with a size up to 120
      nm. In this study, I first characterize the formation of hexagonal platelet-like
      magnetite of a few hundred nanometers in cultures of Thermoanaerobacter spp.
      strain TOR39. Biogenic magnetite with such large crystal sizes and unique
      morphology has never been observed in abiotic or biotic processes and thus can be
      considered as a potential biosignature for thermophilic iron-reducing bacteria.
      The unique crystallographic features and strong ferrimagnetic properties of these
      crystals allow easy and rapid screening for the previous presence of iron
      reducing bacteria in deep terrestrial crustal samples that are unsuitable for
      biological detection methods and, also, the search for biogenic magnetite in
      banded iron formations that deposited only in the first 2 billion years of Earth
      with evidence of life.

PMID- 23145574
TI  - Atomistic structure of cobalt-phosphate nanoparticles for catalytic water
      oxidation.
AB  - Solar-driven water splitting is a key photochemical reaction that underpins the
      feasible and sustainable production of solar fuels. An amorphous cobalt-phosphate
      catalyst (Co-Pi) based on earth-abundant elements has been recently reported to
      efficiently promote water oxidation to protons and dioxygen, a main bottleneck
      for the overall process. The structure of this material remains largely unknown.
      We here exploit ab initio and classical atomistic simulations combined with
      metadynamics to build a realistic and statistically meaningful model of Co-Pi
      nanoparticles. We demonstrate the emergence and stability of molecular-size
      ordered crystallites in nanoparticles initially formed by a disordered Co-O
      network and phosphate groups. The stable crystallites consist of bis-oxo-bridged
      Co centers that assemble into layered structures (edge-sharing CoO(6) octahedra)
      as well as in corner- and face-sharing cubane units. These layered and cubane
      motifs coexist in the crystallites, which always incorporate disordered phosphate
      groups at the edges. Our computational nanoparticles, although limited in size to
      ~1 nm, can contain more than one crystallite and incorporate up to 18 Co centers
      in the cubane/layered structures. The crystallites are structurally stable up to
      high temperatures. We simulate the extended X-ray absorption fine structure
      (EXAFS) of our nanoparticles. Those containing several complete and incomplete
      cubane motifs-which are believed to be essential for the catalytic activity
      display a very good agreement with the experimental EXAFS spectra of Co-Pi
      grains. We propose that the crystallites in our nanoparticles are reliable
      structural models of the Co-Pi catalyst surface. They will be useful to reveal
      the origin of the catalytic efficiency of these novel water-oxidation catalysts.

PMID- 23145575
TI  - Sex at the margins: parthenogenesis vs. facultative and obligate sex in a
      Neotropical ant.
AB  - Geographic parthenogenesis is a distribution pattern, in which parthenogenetic
      populations tend to live in marginal habitats, at higher latitudes and altitudes
      and island-like habitats compared with the sexual forms. The facultatively
      parthenogenetic ant Platythyrea punctata is thought to exhibit this general
      pattern throughout its wide range in Central America and the Caribbean Islands.
      Workers of P. punctata from the Caribbean produce diploid female offspring from
      unfertilized eggs by thelytokous parthenogenesis, and mated females and males are
      rare. In contrast, workers in one colony from Costa Rica were incapable of
      thelytoky; instead mated workers produced all female offspring. Because sample
      sizes were very low in former studies, we here use microsatellite markers and
      explicit tests of thelytoky to examine the population genetic structure of
      ancestral and derived populations of P. punctata throughout the Caribbean and
      Central America. Populations from the Caribbean islands were fully capable of
      parthenogenesis, and population genetic signatures indicate that this is the
      predominant mode of reproduction, although males are occasionally produced. In
      contrast, the northernmost population on the mainland (Texas) showed signatures
      of sexual reproduction, and individuals were incapable of reproduction by
      thelytoky. Contrary to expectations from a geographic parthenogenesis
      distribution pattern, most parts of the mainland populations were found to be
      facultatively thelytokous, with population genetic signatures of both sexual and
      parthenogenetic reproduction.

PMID- 23145576
TI  - Mechanistic understanding of polycyclic aromatic hydrocarbons (PAHs) from the
      thermal degradation of tires under various oxygen concentration atmospheres.
AB  - The thermal degradation of tires under various oxygen concentrations (7-30%/Bal.
      N(2)) was investigated thermo-gravimetrically at 10  degrees C min(-1) heating
      rate over a temperature range from ambient to 1000  degrees C. Significant mass
      loss (~55%) was observed at the temperature of 300-500  degrees C, where the
      thermal degradation rate was almost identical and independent of oxygen
      concentrations due to simultaneous volatilization and oxidation. A series of gas
      chromatography/mass spectroscopy (GC/MS) measurements taken from the effluent of
      a thermo-gravimetric analysis (TGA) unit at temperature of 300-5000  degrees C
      leads to the overall thermal degradation mechanisms of waste tires and some
      insights for understanding evolution steps of air pollutants including volatile
      organic carbons (VOCs) and polycyclic aromatic hydrocarbons (PAHs). In order to
      describe the fundamental mechanistic behavior on tire combustion, the main
      constituents of tires, styrene butadiene rubber (SBR) and polyisoprene (IR), has
      been investigated in the same experimental conditions. The thermal degradation of
      SBR and IR suggests the reaction mechanisms including bond scissions followed by
      hydrogenation, gas phase addition reaction, and/or partial oxidation.

PMID- 23145577
TI  - Chandelier anterior chamber endoillumination-assisted phacoemulsification in eyes
      with corneal opacities.

PMID- 23145578
TI  - Fast-track rehabilitation after robot-assisted laparoscopic cystectomy
      accelerates postoperative recovery.
AB  - WHAT'S KNOWN ON THE SUBJECT? AND WHAT DOES THE STUDY ADD?: There is evidence from
      large abdominal surgeries and some open cystectomy series that multifactorial
      fast-track regimens shorten postoperative convalescence without any effect on
      morbidity and mortality. Such a regimen is of particular interest in combination
      with minimally invasive techniques, as early patient recovery demands for more
      rapid nutrition and mobilisation schemes. The present study, in a single
      institution, reports on the design, application and results of a fast-track
      protocol in patients undergoing robot-assisted laparoscopic cystectomy. There was
      no evidence of a higher incidence of complications with the fast-track regimen
      and postoperative recovery was faster. OBJECTIVES: To evaluate the feasibility
      and effectiveness of a multifactorial fast-track (FT) regimen on perioperative
      outcomes in patients undergoing robot-assisted laparoscopic cystectomy (RALC)
      with extracorporeal urinary diversion. To point out that morbidity and mortality
      of radical cystectomy have improved markedly over the last decades and RALC is an
      emerging technique showing further advances in postoperative recovery, thus
      demanding for more rapid nutrition and mobilisation schemes. PATIENTS AND
      METHODS: A non-randomised cohort study of 63 patients who underwent RALC at one
      institution between January 2007 and March 2010. In all, 31 patients underwent
      RALC without FT and 31 RALC with FT. One patient required conversion to open
      surgery and was therefore excluded from the study. The FT regimen included early
      nutrition and the quickest possible mobilisation, while mechanical bowel
      preparation before surgery, as well as preoperative fasting and nasogastric or
      abdominal drains after surgery, were omitted. Demographics, perioperative and
      complication data (according to modified Clavien system), as well as required
      opioid pain medication were documented prospectively and compared between RALC
      patients with and without FT. RESULTS: Groups were comparable for demographics,
      risk factors and clinical stage as well as operative parameters, e.g. mean
      operating room time, estimated blood loss, lymph nodes removed and postoperative
      haemoglobin level. In the FT group, abdominal drains were mostly omitted and
      nasogastric tubes were removed immediately after surgery. There were significant
      differences in the mobilisation within the room (17.5 vs 31.2 h), the time to a
      regular diet (4.0 vs 6.6 days) and a remarkably lower use of postoperative
      morphine equivalents (57.3 vs 92.4 mg) for patients receiving FT. There were no
      significant differences in the overall complication rates or major complications
      based on Clavien classification. The informative value of the study is limited by
      its single-centre, non-randomised design, a relatively small sample size and a
      possible learning curve bias. CONCLUSIONS: Combining RALC with FT is feasible in
      the perioperative treatment of these patients. Multifactorial postoperative
      regimens seem to quicken postoperative recovery of RALC patients without
      increasing their risk of postoperative complications.

PMID- 23145579
TI  - Understanding the structure of humpback whale songs (L).
AB  - Structured sound sequences produced by humpback whales are described in the
      literature as hierarchically organized songs. Despite the prevalence of such
      descriptions, there is no direct evidence that humpback songs are hierarchically
      structured. It is suggested here that songs may instead be heterarchically
      structured, in which case traditional approaches to analyzing songs may obscure
      their organizational and acoustical features. An alternative framework for
      characterizing patterns within songs is presented, derived from models of
      humpback whale sound production, that characterizes rhythmic and sequential
      regularities in the sound sequences produced by singing whales in terms of
      interacting cycles of breathing and internal air recirculation.

PMID- 23145580
TI  - On the sound absorption by openings in rooms (L).
AB  - Sound absorption by openings has been rarely considered in room acoustics. In
      fact, information about small openings (such as ventilation grids) may sometimes
      be found, but nothing is said about larger openings, possibly as a consequence of
      the less likely occurrence in a design. In order to fill this gap, measurements
      were carried out in scale models, measuring the equivalent absorption due to
      different openings and comparing it with theoretical results. A "practical"
      model, showing a simple dependence on the opening dimension, was finally obtained
      and subsequently validated by measurements in a real room.

PMID- 23145581
TI  - Humpback whale (Megaptera novaeangliae) singers in Hawaii are attracted to
      playback of similar song (L).
AB  - The use of playback experiments to study humpback whale song was assessed.
      Singers clearly detected playback song while singing and with other singers in
      the distance. Singers approached or joined song similar to their own from as far
      as 800 m but did not do so for a different (foreign) song. In one compound trial,
      on the playback of different song, the singer moved away and continued singing;
      when the playback was changed to similar song, it stopped singing and joined the
      playback speaker. Song playback experiments on the breeding grounds are viable
      and may provide insight into song function.

PMID- 23145582
TI  - Effects of diotic fringes on interaural disparity detection (L).
AB  - Detection thresholds were measured for interaural time differences (ITDs) and
      interaural level differences (ILDs) that were carried by probe segments embedded
      in otherwise diotic broadband noise (fringe). The duration of the probe was
      varied between 5 and 200 ms, and the duration of the fringe was between 5 and 100
      ms. Consistent with results of Akeroyd and Bernstein [(2001). J. Acoust. Soc. Am.
      110, 2516-2526], it was found that a 5-ms fringe placed before a 5-ms probe
      (forward fringe) led to a larger threshold elevation than a 5-ms fringe placed
      after the probe (backward fringe). As suggested by Akeroyd and Bernstein, this
      effect was accounted for by a model providing an onset emphasis of a factor of 2.
      In contrast, for longer probe and fringe durations, which have not been tested
      before, a backward fringe had a stronger effect than a forward fringe. This
      surprising effect was accounted for by an extended model that provided an offset
      emphasis of a factor of 11 for a 50-ms probe and a 100-ms fringe.

PMID- 23145583
TI  - Thermal and viscous effects on sound waves: revised classical theory.
AB  - In this paper the recently developed, bi-velocity model of fluid mechanics based
      on the principles of linear irreversible thermodynamics (LIT) is applied to sound
      propagation in gases taking account of first-order thermal and viscous
      dissipation effects. The results are compared and contrasted with the classical
      Navier-Stokes-Fourier results of Pierce for this same situation cited in his
      textbook. Comparisons are also made with the recent analyses of Dadzie and Reese,
      whose molecularly based sound propagation calculations furnish results virtually
      identical with the purely macroscopic LIT-based bi-velocity results below, as
      well as being well-supported by experimental data. Illustrative dissipative sound
      propagation examples involving application of the bi-velocity model to several
      elementary situations are also provided, showing the disjoint entropy mode and
      the additional, evanescent viscous mode.

PMID- 23145584
TI  - Acoustic wave propagation in equivalent fluid macroscopically inhomogeneous
      materials.
AB  - A one-dimensional problem of propagation of plane harmonic wave in
      macroscopically inhomogeneous materials is analyzed. A general description is
      proposed for the material of the equivalent fluid type characterized locally by
      two acoustical parameters: the wavenumber and the acoustical impedance. The
      coupled system of ordinary differential equations for amplitudes of forward and
      backward waves is derived. As an example the problem of wave interaction with a
      layer of inhomogeneous material placed between two homogeneous halfspaces is
      considered. The analytical solution and explicit expressions for reflection and
      transmission coefficients are obtained. It is shown that the presence of the
      inhomogeneous transition layer causes strong frequency dependence on both
      coefficients.

PMID- 23145585
TI  - Non-contact acoustic trapping in circular cross-section glass capillaries: a
      numerical study.
AB  - Ultrasonic particle manipulation has many applications in microfluidic systems.
      Such manipulation is achievable by establishing an ultrasonic standing wave in
      fluid filled micromachined chambers. In this work, the focus is on analyzing the
      trapping potential of water filled capillary tubes actuated ultrasonically. The
      curved walls necessitate the use of a finite element modeling approach. Multiple
      arrangements of the piezoelectric transducers were studied along with the effects
      of changing the capillary and piezoelectric transducer thicknesses. Additionally,
      different modes of driving the piezoelectric transducers were investigated. It
      was found that positioning four piezoelectric transducers equally spaced around
      the capillary tube provided the best force potential field for trapping
      polystyrene spheres in the center of the capillary.

PMID- 23145586
TI  - Discrete vortex model of a Helmholtz resonator subjected to high-intensity sound
      and grazing flow.
AB  - In this paper, a theoretical model is developed to study the acoustical response
      of a Helmholtz resonator as a duct-branched acoustic absorber subjected to both
      high-intensity sound and grazing flow. The present model is comprised of a
      discrete vortex model in combination with a one-dimensional duct sound
      propagation model. The present work is to study the overall effect of incident
      sound interacting with grazing flow but putting emphasis on the nonlinear or
      intermediate regime where the sound intensity has a marked or non-negligible
      influence on the acoustic behavior of the Helmholtz resonator. The numerical
      results reveal that the flow field around the orifice is dominated by the
      evolution of the vortex sheet and the flow pattern is influenced by the ratio of
      the orifice flow velocity to the grazing flow velocity. When the incident sound
      pressure is high or the resonance occurs, the resonator shows nonlinearity, i.e.,
      the acoustic impedance and absorption coefficient vary not only with duct flow
      Mach number buy also with incident frequency and incident sound pressure level.

PMID- 23145587
TI  - Localization of small arms fire using acoustic measurements of muzzle blast
      and/or ballistic shock wave arrivals.
AB  - The accurate localization of small arms fire using fixed acoustic sensors is
      considered. First, the conventional wavefront-curvature passive ranging method,
      which requires only differential time-of-arrival (DTOA) measurements of the
      muzzle blast wave to estimate the source position, is modified to account for
      sensor positions that are not strictly collinear (bowed array). Second, an
      existing single-sensor-node ballistic model-based localization method, which
      requires both DTOA and differential angle-of-arrival (DAOA) measurements of the
      muzzle blast wave and ballistic shock wave, is improved by replacing the basic
      external ballistics model (which describes the bullet's deceleration along its
      trajectory) with a more rigorous model and replacing the look-up table ranging
      procedure with a nonlinear (or polynomial) equation-based ranging procedure.
      Third, a new multiple-sensor-node ballistic model-based localization method,
      which requires only DTOA measurements of the ballistic shock wave to localize the
      point of fire, is formulated. The first method is applicable to situations when
      only the muzzle blast wave is received, whereas the third method applies when
      only the ballistic shock wave is received. The effectiveness of each of these
      methods is verified using an extensive set of real data recorded during a 7 day
      field experiment.

PMID- 23145588
TI  - Broadband sparse-array blind deconvolution using frequency-difference
      beamforming.
AB  - Synthetic time reversal (STR) is a technique for blind deconvolution of receiving
      array recordings of sound from an unknown source in an unknown multipath
      environment. It relies on generic features of multipath sound propagation. In
      prior studies, the pivotal ingredient for STR, an estimate of the source-signal's
      phase (as a function of frequency omega), was generated from conventional
      beamforming of the received-signal Fourier transforms, P(j)(omega), 1 <= j <= N,
      where N is the number of array elements. This paper describes how STR is
      implemented even when the receiving-array elements are many wavelengths apart and
      conventional beamforming is inadequate. Here, the source-signal's phase is
      estimated by beamforming P(j)(*)(omega(1))P(j)(omega(2)) at the difference
      frequency omega(2) - omega(1). This extension of STR is tested with broadband
      signal pulses (11-19 kHz) and a vertical 16-element receiving array having a 3.75
      m-spacing between elements using simple propagation simulations and measured
      results from the FAF06 experiment involving 2.2 km of down slope propagation from
      46 to 92 m water depth. The cross-correlation coefficient between the source
      broadcast and STR-reconstructed-signal waveforms for the simulations and
      experiments are 98% and 91%-92%, respectively. In addition, frequency-difference
      beamforming can be used to determine signal-path-arrival angles that conventional
      beamforming cannot.

PMID- 23145589
TI  - Parallel tempering for strongly nonlinear geoacoustic inversion.
AB  - This paper applies parallel tempering within a Bayesian formulation for strongly
      nonlinear geoacoustic inverse problems. Bayesian geoacoustic inversion consists
      of sampling the posterior probability density (PPD) of seabed parameters to
      estimate integral properties, such as marginal probability distributions, based
      on ocean acoustic data and prior information. This sampling is usually carried
      out using the Markov-chain Monte Carlo method of Metropolis-Hastings sampling.
      However, standard sampling methods can be very inefficient for strongly nonlinear
      problems involving multi-modal PPDs with the potential to miss important regions
      of the parameter space and to significantly underestimate parameter
      uncertainties. Parallel tempering achieves efficient/effective sampling of
      challenging parameter spaces with the ability to transition freely between
      multiple PPD modes by running parallel Markov chains at a series of increasing
      sampling temperatures with probabilistic interchanges between chains. The
      approach is illustrated for inversion of (simulated) acoustic reverberation data
      for which the PPD is highly multi-modal. While Metropolis-Hastings sampling gives
      poor results even with very large sample sizes, parallel tempering provides
      efficient, convergent sampling of the PPD. Methods to enhance the efficiency of
      parallel tempering are also considered.

PMID- 23145590
TI  - Particle filtering for arrival time tracking in space and source localization.
AB  - Locating and tracking a source in an ocean environment and estimating
      environmental parameters of a sound propagation medium are critical tasks in
      ocean acoustics. Many approaches for both are based on full field calculations
      which are computationally intensive and sensitive to assumptions on the structure
      of the environment. Alternative methods that use only select features of the
      acoustic field for localization and environmental parameter estimation have been
      proposed. The focus of this paper is the development of a method that extracts
      arrival times and amplitudes of distinct paths from measured acoustic time-series
      using sequential Bayesian filtering, namely, particle filtering. These
      quantities, along with complete posterior probability density functions, also
      extracted by filtering, are employed in source localization and bathymetry
      estimation. Aspects of the filtering methodology are presented and studied in
      terms of their impact on the uncertainty in the arrival time estimates. Using the
      posterior probability densities of arrival times, source localization and water
      depth estimation are performed for the Haro Strait Primer experiment; the results
      are compared to those of conventional methods. The comparison demonstrates a
      significant advantage in the proposed approach.

PMID- 23145591
TI  - Clutter reduction using Doppler sonar in a harbor environment.
AB  - A high frequency experiment was conducted in the Woods Hole Harbor in
      Massachusetts to evaluate the effectiveness of Doppler sonar for discriminating
      targets from reverberation. Using a pulsed linear frequency modulated signal, one
      finds that the matched filtered outputs are filled with high-level discrete
      backscattered returns, referred to as clutter, which are often confused with the
      target echo. The high level non-target returns have an amplitude distribution
      that is heavy-tailed. Using a Doppler-sensitive binary-phase-shift-keying signal
      coded with an m-sequence, the target echo and clutter can be separated by Doppler
      and delay, and tracked using the Doppler spectrogram (Dopplergram). The Doppler
      filtered time series show a background reverberation with a Rayleigh-like
      amplitude distribution, with an improved signal-to-(peak) reverberation ratio
      compared with that without Doppler filtering. The reduced reverberation level
      with Doppler processing decreases the probability of false alarm (Pfa) for a
      given threshold level. Conversely, for a given Pfa, the higher signal-to-(peak)
      reverberation ratio implies a higher probability of detection. Transmission loss
      measurement was conducted to estimate some of the system parameters, e.g., the
      source level and target strength relative to the noise level.

PMID- 23145592
TI  - Improved calculations of the electromechanical properties of tangentially poled
      stripe-electroded piezoelectric bars and cylinders with nonuniform electric
      fields.
AB  - Tangentially polarized stripe-electroded piezoelectric elements are often used to
      achieve the longitudinal piezoelectric effect without using segmented parts
      bonded together, however the electromechanical properties are not fully realized
      due to the nonuniform electric field and polarization in the element. The
      effective electromechanical coupling coefficient k(3'3eff), piezoelectric modulus
      d(3'3eff), elastic constant s(3'3eff)(E), and relative dielectric constant
      epsilon(3'3eff)(T) (where the prime denotes the nonuniform polarization) for
      tangentially polarized stripe-electroded bars and hollow cylinders are calculated
      using the energy method for the nonuniform electric field. A finite difference
      method is used to analyze the electric field under the assumption that the
      piezoelement is fully polarized. Results are compared with a piecewise linear
      field model and experimental results on representative piezoelements.

PMID- 23145593
TI  - Bistatic, above-critical angle scattering measurements of fully buried unexploded
      ordnance (UXO) and clutter.
AB  - Laboratory grade bistatic scattering measurements are conducted in order to
      examine the acoustic response of realistic fully buried unexploded ordnance (UXO)
      from above-critical angle insonification, between 2 and 40 kHz. A 127 mm diameter
      rocket UXO, a 155 mm diameter artillery shell, a natural rock of approximately
      the same size, and a cinder block are fully buried in water-saturated medium
      grained sand (mean grain diameter, 240 MUm) at depths of 10 cm below the water
      sediment interface. A two-dimensional array of bistatic scattering measurements
      is generated synthetically by scanning a single hydrophone in steps of 3 cm over
      a 1 m * 1 m patch directly above the targets at a height of 20 cm above the water
      sediment interface. Three-dimensional volumetric acoustic images generated from
      the return waveforms reveal scattering components attributed to geometric and
      elastic scattering, as well as multiple-scattering interactions of returns
      between the sediment-water interface and the buried objects. The far-field target
      strength of the objects is estimated through extrapolation of the angular
      spectrum. Agreement is found between experimental data and simulated data
      generated from a finite-element-based, three-dimensional time-harmonic model (2
      25 kHz). Separation of the measured UXO from the clutter objects is demonstrated
      through exploitation of structural-acoustics-based features.

PMID- 23145594
TI  - Narrow sidebranch arrays for low frequency duct noise control.
AB  - The present study investigates the sound transmission loss across a section of an
      infinitely long duct where one or more narrow sidebranch tubes are installed
      flushed with the duct wall. The finite-element method is used to compute the wave
      propagation characteristics, and a simplified theoretical analysis is carried out
      at the same time to explain the wave mechanism at frequencies of high sound
      reduction. Results show that the high sound transmission loss at a particular
      frequency is due to the concerted actions of three consecutive sidebranch tubes
      with the most upstream one in the resonant state. The expansion chamber effect of
      the setup also plays a role in enhancing sound attenuation at non-resonance
      frequencies. Broadband performance of the device can be greatly enhanced by
      appropriate arrangements of tube lengths and/or by coupling arrays on the two
      sides of the duct.

PMID- 23145595
TI  - Sample-based engine noise synthesis using an enhanced pitch-synchronous overlap
      and-add method.
AB  - An algorithm for the real time synthesis of internal combustion engine noise is
      presented. Through the analysis of a recorded engine noise signal of continuously
      varying engine speed, a dataset of sound samples is extracted allowing the real
      time synthesis of the noise induced by arbitrary evolutions of engine speed. The
      sound samples are extracted from a recording spanning the entire engine speed
      range. Each sample is delimitated such as to contain the sound emitted during one
      cycle of the engine plus the necessary overlap to ensure smooth transitions
      during the synthesis. The proposed approach, an extension of the PSOLA method
      introduced for speech processing, takes advantage of the specific periodicity of
      engine noise signals to locate the extraction instants of the sound samples.
      During the synthesis stage, the sound samples corresponding to the target engine
      speed evolution are concatenated with an overlap and add algorithm. It is shown
      that this method produces high quality audio restitution with a low computational
      load. It is therefore well suited for real time applications.

PMID- 23145596
TI  - Annoyance and self-reported sleep disturbance due to night-time railway noise
      examined in the field.
AB  - Railway noise interferes with daytime activities and disturbs sleep leading to
      annoyance of exposed residents. The main objective of this paper was to establish
      exposure-response relationships between nocturnal railway noise exposure and
      annoyance and to examine self-reported sleep disturbances as short-term reactions
      to noise. In a field study 33 residents living close to railway tracks in the
      Cologne/Bonn area (Germany) were investigated. Railway noise was measured indoors
      during nine consecutive nights at each site. Questionnaires referring to
      annoyance and non-acoustical factors were performed. Annoyance ratings increased
      significantly with the total number of trains and freight trains per night, and
      non-significantly with rising number of passenger trains and energy equivalent
      sound pressure level (L(Aeq)), when adjusting the model for non-acoustical
      variables. The total number of trains and the number of freight trains also
      significantly affected self-reported awakening frequency, but no other aspects of
      subjective sleep disturbances. The responses of this subject sample referring to
      railway noise in the previous night point to rather low impairments of exposed
      residents.

PMID- 23145597
TI  - Brown meagre vocalization rate increases during repetitive boat noise exposures:
      a possible case of vocal compensation.
AB  - This study investigated whether or not boat noise causes variations in brown
      meagre (Sciaena umbra) vocalizations recorded in a nearshore Mediterranean marine
      reserve. Six nocturnal experimental sessions were carried out from June to
      September 2009. In each of them, a recreational boat passed over vocalizing fish
      6 times with 1 boat passage every 10 min. For this purpose three different boats
      were used in random order: an 8.5-m cabin-cruiser (CC), a 5-m fiberglass boat
      (FB), and a 7-m inflatable boat (INF). In situ continuous acoustic recordings
      were collected using a self-standing sonobuoy. Because boat noise levels largely
      exceeded both background noise and S. umbra vocalizations in the species' hearing
      frequency range, masking of acoustic communication was assumed. Although no
      immediate effect was observed during a single boat passage, the S. umbra mean
      pulse rate increased over multiple boat passages in the experimental condition
      but not in the control condition, excluding that the observed effect was due to a
      natural rise in fish vocalizations. The observed vocal enhancement may result
      either from an increased density of callers or from an increased number of
      pulses/sounds produced by already acoustically active individuals, as a form of
      vocal compensation. These two explanations are discussed.

PMID- 23145598
TI  - Implementation of diffraction in a ray-tracing model for the prediction of noise
      in open-plan offices.
AB  - Sound prediction in open-plan offices is a real challenge because of the
      complexity of the layout of such offices, and therefore because of the multitude
      of acoustic phenomena involved. One such phenomenon, of primary importance, and
      not the least challenging of them, is the diffraction by screens and low dividers
      that usually partition the workspace. This paper describes implementing the
      equations of the Uniform Theory of Diffraction [McNamara et al. (1990).
      Introduction to the Uniform Theory of Diffraction (Artech House, Boston)] in an
      existing ray-tracing model initially dedicated to sound prediction in industrial
      premises. For the purposes of validation, a series of measurements was conducted
      in a semi-anechoic chamber in the same manner as Wang and Bradley [(2002). Appl.
      Acoust. 63, 849-866] but including real desktops instead of single screens. A
      first phase was dedicated to controlling the quality of the installation by
      making comparisons with McNamara's solution for a single screen on a rigid floor.
      Then, the validation itself was conducted with measurements on real desktops,
      first without a ceiling, and then with a rigid ceiling suspended above the double
      desk. The results of the comparisons between calculations and measurements in
      this configuration have demonstrated that the model is an effective tool for
      predicting sound levels in an open-plan office.

PMID- 23145599
TI  - Acoustic properties of plates with unevenly distributed macroperforations backed
      by woven meshes.
AB  - A hybrid model describing the acoustic properties of plates with
      macroperforations that can be unevenly distributed on the plate surface and
      backed by woven or precision woven meshes with microscopic perforations is
      proposed. The plate perforations may be of circular or rectangular shapes. Since
      the perforated plate may not necessarily be considered as an equivalent fluid,
      its impedance is calculated by the Maa model [Noise Control Eng. J. 29, 77-84
      (1987)], whereas the Johnson-Champoux-Allard model [J. Appl. Phys. 70, 1975-1979
      (1991)] is used for the mesh, considered as an equivalent fluid. A simple model
      for the elementary cell of the mesh structure is proposed in order to calculate
      parameters that can be considered as the thermal characteristic length Lambda'
      and the viscous characteristic length Lambda. An effective airflow resistivity is
      introduced to account for the increase of particle velocity through the mesh
      placed behind the carrying macroperforated plate and is used in the transfer
      matrix approach to obtain the impedance of the whole multilayer system. The
      hybrid model seems to represent a good approach of this multilayer system. The
      theoretical predictions are compared with experimental measurements.

PMID- 23145600
TI  - Disentangling preference ratings of concert hall acoustics using subjective
      sensory profiles.
AB  - Subjective evaluation of acoustics was studied by recording nine concert halls
      with a simulated symphony orchestra on a seat 12 m from the orchestra. The
      recorded music was spatially reproduced for subjective listening tests and
      individual vocabulary profiling. In addition, the preferences of the assessors
      and objective parameters were gathered. The results show that concert halls were
      discriminated using perceptual characteristics, such as Envelopment/Loudness,
      Reverberance, Bassiness, Proximity, Definition, and Clarity. With these
      perceptual dimensions the preference ratings can be explained. Seventeen
      assessors were divided into two groups based on their preferences. The first
      group preferred concert halls with relatively intimate sound, in which it is
      quite easy to hear individual instruments and melody lines. In contrast, the
      second group preferred a louder and more reverberant sound with good envelopment
      and strong bass. Even though all halls were recorded exactly at the same
      distance, the preference is best explained with subjective Proximity and with
      Bassiness, Envelopment, and Loudness to some extent. Neither the preferences nor
      the subjective ratings could be fully explained by objective parameters (ISO3382
      1:2009), although some correlations were found.

PMID- 23145601
TI  - A modal-based reduction method for sound absorbing porous materials in poro
      acoustic finite element models.
AB  - Structural-acoustic finite element models including three-dimensional (3D)
      modeling of porous media are generally computationally costly. While being the
      most commonly used predictive tool in the context of noise reduction
      applications, efficient solution strategies are required. In this work, an
      original modal reduction technique, involving real-valued modes computed from a
      classical eigenvalue solver is proposed to reduce the size of the problem
      associated with the porous media. In the form presented in this contribution, the
      method is suited for homogeneous porous layers. It is validated on a 1D poro
      acoustic academic problem and tested for its performance on a 3D application,
      using a subdomain decomposition strategy. The performance of the proposed method
      is estimated in terms of degrees of freedom downsizing, computational time
      enhancement, as well as matrix sparsity of the reduced system.

PMID- 23145602
TI  - A numerical investigation of the Fick's law of diffusion in room acoustics.
AB  - In this paper the validity of the Fick's law of diffusion in room acoustics is
      investigated in the stationary state. The Fick's law, underlying the room
      acoustics diffusion model, assumes a proportionality relationship between the
      local sound intensity and the energy density gradient, the proportionality
      constant being the so-called diffusion coefficient. This relationship, based on
      an analogy with the behavior of real particles in a scattering medium, is
      assessed by using a numerical tool simulating the actual dynamics of sound
      particles in a room. Two types of room geometries are considered: rooms with
      proportionate dimensions and long rooms. Concerning proportionate rooms the
      numerical analysis highlights the presence of weak variations of the reverberant
      energy density, generating an intensity vector pattern which is shown to be
      correctly described by the theoretical Fick's law and homogeneous diffusion.
      Conversely, inside long rooms, an estimate of the local value of the diffusion
      coefficient is carried out, showing that the reverberant sound field is well
      described by a spatially varying diffusion coefficient (non-homogeneous
      diffusion). The rate of increase of the estimated diffusion coefficient depends
      on the cross-sectional area of the room and on the boundaries absorption
      coefficient.

PMID- 23145603
TI  - An immersed boundary computational model for acoustic scattering problems with
      complex geometries.
AB  - An immersed boundary computational model is presented in order to deal with the
      acoustic scattering problem by complex geometries, in which the wall boundary
      condition is treated as a direct body force determined by satisfying the non
      penetrating boundary condition. Two distinct discretized grids are used to
      discrete the fluid domain and immersed boundary, respectively. The immersed
      boundaries are represented by Lagrangian points and the direct body force
      determined on these points is applied on the neighboring Eulerian points. The
      coupling between the Lagrangian points and Euler points is linked by a discrete
      delta function. The linearized Euler equations are spatially discretized with a
      fourth-order dispersion-relation-preserving scheme and temporal integrated with a
      low-dissipation and low-dispersion Runge-Kutta scheme. A perfectly matched layer
      technique is applied to absorb out-going waves and in-going waves in the immersed
      bodies. Several benchmark problems for computational aeroacoustic solvers are
      performed to validate the present method.

PMID- 23145604
TI  - Time reversal communication over doubly spread channels.
AB  - Conventional time reversal can mitigate multipath delay dispersion by temporal
      focusing. But it is not applicable to time-varying channels with a Doppler
      spread. Although recently time reversal communication has been adapted to time
      variant channels, the modified technique requires frequent channel updates to
      track channel variations and cannot handle large Doppler spread, which means that
      it cannot achieve frequency focusing. In this paper, two time reversal receivers
      for underwater acoustic communications over doubly spread channels are proposed.
      The proposed approach, which can be interpreted as time-frequency channel
      matching, is based on the channel spreading function rather than impulse response
      adopted by the existing techniques; this leads to much less frequent channel
      updates. Unlike existing methods that only correct a single Doppler shift, the
      proposed approach uses a rake-like structure to compensate for multiple Doppler
      shifts and hence can eliminate severe Doppler spread induced by temporal channel
      variations. Simulation results verify the effectiveness of the proposed approach,
      indicating that it can simultaneously counteract delay and Doppler spreads,
      achieving both temporal and frequency focusing.

PMID- 23145605
TI  - Cross-correlations of diffuse noise in an ocean environment using eigenvalue
      based statistical inference.
AB  - Cross-correlations of diffuse noise fields can be used to extract environmental
      information. The influence of directional sources (usually ships) often results
      in a bias of the travel time estimates obtained from the cross-correlations.
      Using an array of sensors, insights from random matrix theory on the behavior of
      the eigenvalues of the sample covariance matrix (SCM) in an isotropic noise field
      are used to isolate the diffuse noise component from the directional sources. A
      sequential hypothesis testing of the eigenvalues of the SCM reveals eigenvalues
      dominated by loud sources that are statistical outliers for the assumed diffuse
      noise model. Travel times obtained from cross-correlations using only the diffuse
      noise component (i.e., by discarding or attenuating the outliers) converge to the
      predicted travel times based on the known array sensor spacing and measured sound
      speed at the site and are stable temporally (i.e., unbiased estimates). Data from
      the Shallow Water 2006 experiment demonstrates the effectiveness of this approach
      and that the signal-to-noise ratio builds up as the square root of time, as
      predicted by theory.

PMID- 23145606
TI  - Bayesian three-dimensional reconstruction of toothed whale trajectories: passive
      acoustics assisted with visual and tagging measurements.
AB  - The author describes and evaluates a Bayesian method to reconstruct three
      dimensional toothed whale trajectories from a series of echolocation signals.
      Localization by using passive acoustic data (time of arrival of source signals at
      receptors) is assisted by using visual data (coordinates of the whale when diving
      and resurfacing) and tag information (movement statistics). The efficiency of the
      Bayesian method is compared to the standard minimum mean squared error
      statistical approach by comparing the reconstruction results of 48 simulated
      sperm whale (Physeter macrocephalus) trajectories. The use of the advanced
      Bayesian method reduces bias (standard deviation) with respect to the standard
      method up to a factor of 8.9 (13.6). The author provides open-source software
      which is functional with acoustic data which would be collected in the field from
      any three-dimensional receptor array design. This approach renews passive
      acoustics as a valuable tool to study the underwater behavior of toothed whales.

PMID- 23145607
TI  - Short-term acoustic forecasting via artificial neural networks for neonatal
      intensive care units.
AB  - Noise levels in hospitals, especially neonatal intensive care units (NICUs), have
      become of great concern for hospital designers. This paper details an artificial
      neural network (ANN) approach to forecasting the sound loads in NICUs. The ANN is
      used to learn the relationship between past, present, and future noise levels. By
      training the ANN with data specific to the location and device used to measure
      the sound, the ANN is able to produce reasonable predictions of noise levels in
      the NICU. Best case results show average absolute errors of 5.06 +/- 4.04% when
      used to predict the noise levels one hour ahead, which correspond to 2.53 dBA +/-
      2.02 dBA. The ANN has the tendency to overpredict during periods of stability and
      underpredict during large transients. This forecasting algorithm could be of use
      in any application where prediction and prevention of harmful noise levels are of
      the utmost concern.

PMID- 23145608
TI  - Bayesian space-frequency separation of wide-band sound sources by a hierarchical
      approach.
AB  - This paper proposes an efficient solution to the separation of uncorrelated wide
      band sound sources which overlap each other in both space and frequency domains.
      The space-frequency separation is solved in a hierarchical way by (1) expanding
      the sound sources onto a set of spatial basis functions whose coefficients become
      the unknowns of the problem (backpropagation step) and (2) blindly demixing the
      coefficients of the spatial basis into uncorrelated components relating to
      sources of distinct physical origins (separation step). The backpropagation and
      separation steps are both investigated from a Bayesian perspective. In
      particular, Markov Chain Monte Carlo sampling is advocated to obtain Bayesian
      estimates of the separated sources. Separation is guaranteed for sound sources
      having different power spectra and sufficiently smooth spatial modes with respect
      to frequency. The validity and efficiency of the proposed separation procedure
      are demonstrated on laboratory experiments.

PMID- 23145609
TI  - Nested sampling applied in Bayesian room-acoustics decay analysis.
AB  - Room-acoustic energy decays often exhibit single-rate or multiple-rate
      characteristics in a wide variety of rooms/halls. Both the energy decay order and
      decay parameter estimation are of practical significance in architectural
      acoustics applications, representing two different levels of Bayesian
      probabilistic inference. This paper discusses a model-based sound energy decay
      analysis within a Bayesian framework utilizing the nested sampling algorithm. The
      nested sampling algorithm is specifically developed to evaluate the Bayesian
      evidence required for determining the energy decay order with decay parameter
      estimates as a secondary result. Taking the energy decay analysis in
      architectural acoustics as an example, this paper demonstrates that two different
      levels of inference, decay model-selection and decay parameter estimation, can be
      cohesively accomplished by the nested sampling algorithm.

PMID- 23145611
TI  - A model for the relation between stimulus frequency and spontaneous otoacoustic
      emissions in lizard papillae.
AB  - Spontaneous otoacoustic emissions (SOAEs) and stimulus frequency otoacoustic
      emissions (SFOAEs) have been described from lizard ears. Although there are
      several models for these systems, none has modeled the characteristics of both of
      these types of otoacoustic emissions based upon their being derived from hair
      cells as active oscillators. Data from the ears of two lizard species, one
      lacking a tectorial membrane and one with a chain of tectorial sallets, as
      described by Bergevin et al. ["Coupled, active oscillators and lizard otoacoustic
      emissions," AIP Conf. Proc. 1403, 453 (2008)], are modeled as an array of coupled
      self-sustained oscillators. The model, originally developed by Vilfan and Duke
      ["Frequency clustering in spontaneous otoacoustic emissions from a lizard's ear,"
      Biophys. J. 95, 4622-4630 (2008)], well describes both the amplitude and phase
      characteristics of SFOAEs and the relation between SFOAEs and SOAEs.

PMID- 23145610
TI  - A prediction of the minke whale (Balaenoptera acutorostrata) middle-ear transfer
      function.
AB  - The lack of baleen whale (Cetacea Mysticeti) audiograms impedes the assessment of
      the impacts of anthropogenic noise on these animals. Estimates of audiograms,
      which are difficult to obtain behaviorally or electrophysiologically for baleen
      whales, can be made by simulating the audiogram as a series of components
      representing the outer, middle, and inner ear (Rosowski, 1991; Ruggero and
      Temchin, 2002). The middle-ear portion of the system can be represented by the
      middle-ear transfer function (METF), a measure of the transmission of acoustic
      energy from the external ear to the cochlea. An anatomically accurate finite
      element model of the minke whale (Balaenoptera acutorostrata) middle ear was
      developed to predict the METF for a mysticete species. The elastic moduli of the
      auditory ossicles were measured by using nanoindentation. Other mechanical
      properties were estimated from experimental stiffness measurements or from
      published values. The METF predicted a best frequency range between approximately
      30 Hz and 7.5 kHz or between 100 Hz and 25 kHz depending on stimulation location.
      Parametric analysis found that the most sensitive parameters are the elastic
      moduli of the glove finger and joints and the Rayleigh damping stiffness
      coefficient beta. The predicted hearing range matches well with the vocalization
      range.

PMID- 23145612
TI  - In-plane motions of the stapes in human ears.
AB  - The piston-like (translation normal to the footplate) and rocking-like (rotation
      along the long and short axes of the footplate) are generally accepted as motion
      components of the human stapes. It has been of issue whether in-plane motions,
      i.e., transversal movements of the footplate in the oval window, are comparable
      to these motion components. In order to quantify the in-plane motions the motion
      at nine points on the medial footplate was measured in five temporal bones with
      the cochlea drained using a three-dimensional (3D) laser Doppler vibrometer. It
      was found that the stapes shows in-plane movements up to 19.1 +/- 8.7% of the
      piston-like motion. By considering possible methodological errors, i.e., the
      effects of the applied reflective glass beads and of alignment of the 3D laser
      Doppler system, such value was reduced to be about 7.4 +/- 3.1%. Further, the in
      plane motions became minimal (~ 4.2 +/- 1.4% of the piston-like motion) in
      another plane, which was anatomically within the footplate. That plane was
      shifted to the lateral direction by 118 MUm, which was near the middle of the
      footplate, and rotated by 4.7 degrees  with respect to the medial footplate
      plane.

PMID- 23145613
TI  - Distortion-product otoacoustic emission suppression tuning curves in hearing
      impaired humans.
AB  - Distortion-product otoacoustic emission (DPOAE) suppression tuning curves (STCs)
      were measured in 65 hearing-impaired (HI) subjects at f(2) frequencies of 2.0,
      2.8, 4.0, and 5.6 kHz and L(2) levels relative to sensation level (SL) from 10 dB
      to as much as 50 dB. Best frequency, cochlear-amplifier gain (tip-to-tail
      difference, T-T), and tuning (Q(ERB)) were estimated from STCs. As with normal
      hearing (NH) subjects, T-T differences and Q(ERB) decreased as L(2) increased. T
      T differences and Q(ERB) were reduced in HI ears (compared to normal) for
      conditions in which L(2) was fixed relative to behavioral threshold (dB SL). When
      STCs were compared with L(2) at constant sound pressure levels (dB SPL),
      differences between NH and HI subjects were reduced. The large effect of level
      and small effect of hearing loss were both confirmed by statistical analyses.
      Therefore, the magnitude of the differences in DPOAE STCs between NH and HI
      subjects is mainly dependent on the manner in which level (L(2)) is specified.
      Although this conclusion may appear to be at odds with previous, invasive
      measures of cochlear-response gain and tuning, the apparent inconsistency may be
      resolved when the manner of specifying stimulus level is taken into account.

PMID- 23145614
TI  - Growth of suppression using distortion-product otoacoustic emission measurements
      in hearing-impaired humans.
AB  - Growth of distortion-product otoacoustic emission suppression was measured in 65
      subjects with mild-to-moderate sensorineural hearing loss (HI). Measurements were
      made at four probe frequencies (f(2)) and up to five L(2) levels. Eleven
      suppressor frequencies (f(3)) were used for each f(2), L(2) combination. These
      data were compared to data from normal-hearing (NH) subjects (Gorga et al.,
      2011a). In both NH and HI subjects, growth of suppression depended on the
      relation between f(2) and f(3), such that the slope was close to one when f(3) ~
      f(2), steeper than one when f(3) < f(2), and shallower than one when f(3) > f(2).
      Differences in growth of suppression between NH and HI subjects were not observed
      for fixed f(2), L(2) combinations, however large differences were observed in
      suppressor "threshold" when compared at the same probe sensation level (dB SL).
      Smaller group differences were observed when compared at the same probe sound
      pressure level (dB SPL). Therefore, the extent of these differences depended on
      how probe level (L(2)) was specified. When the results from NH and HI subjects
      are compared with each other and with psychophysical studies of masking,
      differences are observed that have implications for the remediation of mild-to
      moderate hearing loss.

PMID- 23145615
TI  - Moments of click-evoked otoacoustic emissions in human ears: group delay and
      spread, instantaneous frequency and bandwidth.
AB  - A click-evoked otoacoustic emission (CEOAE) has group delay and spread as first-
      and second-order temporal moments varying over frequency, and instantaneous
      frequency and bandwidth as first- and second-order spectral moments varying over
      time. Energy-smoothed moments were calculated from a CEOAE database over 0.5-15
      kHz bandwidth and 0.25-20 ms duration. Group delay and instantaneous frequency
      were calculated without phase unwrapping using a coherence synchrony measure that
      accurately classified ears with hearing loss. CEOAE moment measurements were
      repeatable in individual ears. Group delays were similar for CEOAEs and stimulus
      frequency OAEs. Group spread is a frequency-specific measure of temporal spread
      in an emission, related to spatial spread across tonotopic generation sites along
      the cochlea. In normal ears, group delay and spread increased with frequency and
      decreased with level. A direct measure of cochlear tuning above 4 kHz was
      analyzed using instantaneous frequency and bandwidth. Synchronized spontaneous
      OAEs were present in most ears below 4 kHz, and confounded interpretation of
      moments. In ears with sensorineural hearing loss, group delay and spread varied
      with audiometric classification and amount of hearing loss; group delay differed
      between older males and females. CEOAE moments reveal clinically relevant
      information on cochlear tuning in ears with normal and impaired hearing.

PMID- 23145616
TI  - Analysis of the cochlear microphonic to a low-frequency tone embedded in filtered
      noise.
AB  - The cochlear microphonic was recorded in response to a 733 Hz tone embedded in
      noise that was high-pass filtered at 25 different frequencies. The amplitude of
      the cochlear microphonic increased as the high-pass cutoff frequency of the noise
      increased. The amplitude growth for a 60 dB SPL tone was steeper and saturated
      sooner than that of an 80 dB SPL tone. The growth for both signal levels,
      however, was not entirely cumulative with plateaus occurring at about 4 and 7 mm
      from the apex. A phenomenological model of the electrical potential in the
      cochlea that included a hair cell probability function and spiral geometry of the
      cochlea could account for both the slope of the growth functions and the plateau
      regions. This suggests that with high-pass-filtered noise, the cochlear
      microphonic recorded at the round window comes from the electric field generated
      at the source directed towards the electrode and not down the longitudinal axis
      of the cochlea.

PMID- 23145617
TI  - Investigating the auditory enhancement phenomenon using behavioral temporal
      masking patterns.
AB  - A narrowband signal is subjected to less masking from a simultaneously presented
      notched masker if it is preceded by a precursor that occupies the same spectral
      region as the masker, a phenomenon referred to as enhancement. The present study
      investigated (i) the amount of enhancement for the detection of a narrowband
      noise added to a notched masker, and (ii) masking patterns associated with the
      detection of tone pips added to the narrowband signal. The resulting
      psychophysical data were compared to predictions generated using a model similar
      to the neural adaptation-of-inhibition model proposed by Nelson and Young
      [(2010b). J. Neurosci. 30, 6577-6587]. The amount of enhancement was measured as
      a function of the temporal separation between the precursor and masker in
      Experiment I, and as a function of precursor level in Experiment II. The model
      captured the temporal dynamics of psychophysical enhancement reasonably well for
      both the long-duration noise signals and the masking patterns. However, in
      contrast to psychophysical data which indicated reliable enhancement only when
      the precursor and masker shared the same levels, the model predicated enhancement
      at all precursor levels.

PMID- 23145618
TI  - Forward masking of frequency modulation.
AB  - Forward masking of sinusoidal frequency modulation (FM) was measured with three
      types of maskers: FM, amplitude modulation (AM), and a masker created by
      combining the magnitude spectrum of an FM tone with random component phases. For
      the signal FM rates used (5, 20, and 40 Hz), an FM masker raised detection
      thresholds in terms of frequency deviation by a factor of about 5 relative to
      without a masker. The AM masker produced a much smaller effect, suggesting that
      FM-to-AM conversion did not contribute substantially to the FM forward masking.
      The modulation depth of an FM masker had a nonmonotonic effect, with maximal
      masking observed at an intermediate value within the range of possible depths,
      while the random-phase FM masker produced less masking, arguing against a
      spectrally-based explanation for FM forward masking. Broad FM-rate selectivity
      for forward masking was observed for both 4-kHz and 500-Hz carriers. Thresholds
      measured as a function of the masker-signal delay showed slow recovery from FM
      forward masking, with residual masking for delays up to 500 ms. The FM forward
      masking effect resembles that observed for AM [Wojtczak and Viemeister (2005). J.
      Acoust. Soc. Am. 188, 3198-3210] and may reflect modulation-rate selective neural
      adaptation to FM.

PMID- 23145619
TI  - Improved perception of speech in noise and Mandarin tones with acoustic
      simulations of harmonic coding for cochlear implants.
AB  - Harmonic and temporal fine structure (TFS) information are important cues for
      speech perception in noise and music perception. However, due to the inherently
      coarse spectral and temporal resolution in electric hearing, the question of how
      to deliver harmonic and TFS information to cochlear implant (CI) users remains
      unresolved. A harmonic-single-sideband-encoder [(HSSE); Nie et al. (2008).
      Proceedings of IEEE International Conference on Acoustics, Speech, and Signal
      Processing; Lie et al., (2010). Proceedings of IEEE International Conference on
      Acoustics, Speech, and Signal Processing] strategy has been proposed that
      explicitly tracks the harmonics in speech and transforms them into modulators
      conveying both amplitude modulation and fundamental frequency information. For
      unvoiced speech, HSSE transforms the TFS into a slowly varying yet still noise
      like signal. To investigate its potential, four- and eight-channel vocoder
      simulations of HSSE and the continuous-interleaved-sampling (CIS) strategy were
      implemented, respectively. Using these vocoders, five normal-hearing subjects'
      speech recognition performance was evaluated under different masking conditions;
      another five normal-hearing subjects' Mandarin tone identification performance
      was also evaluated. Additionally, the neural discharge patterns evoked by HSSE-
      and CIS-encoded Mandarin tone stimuli were simulated using an auditory nerve
      model. All subjects scored significantly higher with HSSE than with CIS vocoders.
      The modeling analysis demonstrated that HSSE can convey temporal pitch cues
      better than CIS. Overall, the results suggest that HSSE is a promising strategy
      to enhance speech perception with CIs.

PMID- 23145620
TI  - Predicting the speech reception threshold of cochlear implant listeners using an
      envelope-correlation based measure.
AB  - A modulation-based index is proposed for predicting speech intelligibility by
      cochlear implant (CI) listeners. The input to the proposed index are speech
      envelopes extracted using the individual CI user's daily strategy, and as such,
      this approach incorporates information about the number of active electrodes,
      shape of the compression function and electrical dynamic range. High correlation
      (r = 0.96) was achieved with the proposed index when evaluated with speech
      reception thresholds (SRTs) obtained by CI users in steady and speech-masker
      conditions. This outcome suggests that the information contained in
      electrodograms seems to be sufficient for reliably predicting CI user's
      performance in noise. The proposed index can be used by clinicians to optimize
      the selection of fitting parameters of individual CI users for better performance
      in noise.

PMID- 23145621
TI  - Consonant recognition as a function of the number of stimulation channels in the
      Hybrid short-electrode cochlear implant.
AB  - Consonant recognition was measured as a function of the number of stimulation
      channels for Hybrid short-electrode cochlear implant (CI) users, long-electrode
      CI users, and normal-hearing (NH) listeners in quiet and background noise. Short
      electrode CI subjects were tested with 1-6 channels allocated to a frequency
      range of 1063-7938 Hz. Long-electrode CI subjects were tested with 1-6, 8, or 22
      channels allocated to 188-7938 Hz, or 1-6 or 15 channels from the basal 15
      electrodes allocated to 1063-7938 Hz. NH listeners were tested with simulations
      of each CI group/condition. Despite differences in intracochlear electrode
      spacing for equivalent channel conditions, all CI subject groups performed
      similarly at each channel condition and improved up to at least four channels in
      quiet and noise. All CI subject groups underperformed relative to NH subjects.
      These preliminary findings suggest that the limited channel benefit seen for CI
      users may not be due solely to increases in channel interactions as a function of
      electrode density. Other factors such as pre-operative patient history, location
      of stimulation in the base versus apex, or a limit on the number of electric
      channels that can be processed cognitively, may also interact with the effects of
      electrode contact spacing along the cochlea.

PMID- 23145622
TI  - Measuring decision weights in recognition experiments with multiple response
      alternatives: comparing the correlation and multinomial-logistic-regression
      methods.
AB  - Psychophysical "reverse-correlation" methods allow researchers to gain insight
      into the perceptual representations and decision weighting strategies of
      individual subjects in perceptual tasks. Although these methods have gained
      momentum, until recently their development was limited to experiments involving
      only two response categories. Recently, two approaches for estimating decision
      weights in m-alternative experiments have been put forward. One approach extends
      the two-category correlation method to m > 2 alternatives; the second uses
      multinomial logistic regression (MLR). In this article, the relative merits of
      the two methods are discussed, and the issues of convergence and statistical
      efficiency of the methods are evaluated quantitatively using Monte Carlo
      simulations. The results indicate that, for a range of values of the number of
      trials, the estimated weighting patterns are closer to their asymptotic values
      for the correlation method than for the MLR method. Moreover, for the MLR method,
      weight estimates for different stimulus components can exhibit strong
      correlations, making the analysis and interpretation of measured weighting
      patterns less straightforward than for the correlation method. These and other
      advantages of the correlation method, which include computational simplicity and
      a close relationship to other well-established psychophysical reverse-correlation
      methods, make it an attractive tool to uncover decision strategies in m
      alternative experiments.

PMID- 23145623
TI  - Vibratory responses of synthetic, self-oscillating vocal fold models.
AB  - The flow-induced responses of four self-oscillating synthetic vocal fold models
      are compared. All models were life-sized and fabricated using flexible silicone
      compounds with material properties comparable to those of human vocal fold
      tissue. Three of the models had two layers of different stiffness to represent
      the body-cover grouping of vocal fold tissue. Two of the two-layer models were
      based on the "M5" geometry [Scherer et al., J. Acoust. Soc. Am. 109, 1616-1630
      (2001)], while the third was based on magnetic resonance imaging data. The fourth
      model included several layers, including a thin epithelial layer, an exceedingly
      flexible superficial lamina propria layer, a ligament layer that included an
      anteriorly-posteriorly oriented fiber to restrict vertical motion, and a body
      layer. Measurements were performed with these models in full larynx and
      hemilarynx configurations. Data included onset pressure, vibration frequency,
      glottal flow rate, maximum glottal width, and medial surface motion, the latter
      two of which were acquired using high-speed imaging techniques. The fourth, multi
      layer model exhibited onset pressure, frequency, and medial surface motion traits
      that are comparable to published human vocal fold data. Importantly, the model
      featured an alternating convergent-divergent glottal profile and mucosal wave
      like motion, characteristics which are important markers of human vocal fold
      vibration.

PMID- 23145625
TI  - Vowel normalization and the perception of speaker changes: an exploration of the
      contextual tuning hypothesis.
AB  - Many experiments have reported a perceptual advantage for vowels presented in
      blocked-versus mixed-voice conditions. Nusbaum and colleagues [Nusbaum and Morin
      (1992). in Speech Perception, Speech Production, and Linguistic Structure, edited
      by Y. Tohkura, Y. Sagisaka, and E. Vatikiotis-Bateson (OHM, Tokyo), pp. 113-134;
      Magnuson and Nusbaum (2007). J. Exp. Psychol. Hum. Percept. Perform. 33(2), 391
      409] present results which suggest that the size of this advantage may be related
      to the facility with which listeners can detect speaker changes, so that
      combinations of less similar voices can result in better performance than
      combinations of more similar voices. To test this, a series of synthetic voices
      (differing in their source characteristics and/or formant-spaces) was used in a
      speeded-monitoring task. Vowels were presented in blocks made up of tokens from
      one or two synthetic voices. Results indicate that formant-space differences, in
      the absence of source differences between voices in a block, were unlikely to
      result in the perception of multiple voices, leading to lower accuracy and
      relatively faster reaction times. Source differences between voices in a block
      resulted in the perception of multiple voices, increased reaction times, and a
      decreased negative effect of formant-space differences between voices on
      identification accuracy. These results are consistent with a process in which the
      detection of speaker changes guides the appropriate or inappropriate use of
      extrinsic information in normalization.

PMID- 23145624
TI  - Voiced stop prenasalization in two dialects of Greek.
AB  - This study examined the phonetic realization of voiced stops in the Cretan and
      Thessalonikan dialects of Modern Greek. Six males and six females of each dialect
      were recorded in a sentence-reading task. Duration and amplitude were measured to
      compare the degree of nasality of voiced stops to that of nasals in different
      phonetic contexts. Results showed that amplitude changes during the voicing bar
      of the voiced stops varied both within and across speakers. In some instances,
      there was consistently low amplitude throughout the voicing bar (characteristic
      of voiced stops), whereas in other instances, there was high amplitude at the
      closure onset followed by decreasing amplitude toward the burst (characteristic
      of prenasalization). By contrast, nasals had consistently high amplitude
      throughout the murmur. The mixed-effects models suggest that there were complex
      and interactive influences of dialect, gender, prosodic position, and stress in
      realizing prenasality in the voiced stops. In particular, Cretan male speakers
      showed the least clear tendency of prenasalization consistent with earlier
      impressionistic studies. Furthermore, productions of Cretan males showed less
      prenasalization than those of females in both prosodic positions. The procedures
      in this study can be used to describe prenasalization in other dialects or
      languages where prenasalization has been observed.

PMID- 23145627
TI  - A classification based approach to speech segregation.
AB  - A key problem in computational auditory scene analysis (CASA) is monaural speech
      segregation, which has proven to be very challenging. For monaural mixtures, one
      can only utilize the intrinsic properties of speech or interference to segregate
      target speech from background noise. Ideal binary mask (IBM) has been proposed as
      a main goal of sound segregation in CASA and has led to substantial improvements
      of human speech intelligibility in noise. This study proposes a classification
      approach to estimate the IBM and employs support vector machines to classify time
      frequency units as either target- or interference-dominant. A re-thresholding
      method is incorporated to improve classification results and maximize hit minus
      false alarm rates. An auditory segmentation stage is utilized to further improve
      estimated masks. Systematic evaluations show that the proposed approach produces
      high quality estimated IBMs and outperforms a recent system in terms of
      classification accuracy.

PMID- 23145626
TI  - Comparing behavioral discrimination and learning abilities in monolinguals,
      bilinguals and multilinguals.
AB  - The aim of the experiment was to determine whether language learning experience
      contributes to the development of enhanced speech perception abilities.
      Monolinguals, bilinguals and multilinguals were compared in their ability to
      discriminate a non-native contrast behaviorally using an AX task. The experiment
      was based on a "pre-test-training-post-test" design and performance was tested
      before and after receiving training on the voiceless aspirated dental/retroflex
      stop contrast. At post-test, participants were also tested on their ability to
      transfer training to a similar contrast (i.e., voiceless unaspirated
      dental/retroflex stop contrast). While no group differences were found at pre
      test, analyses of the trained-on contrast at post-test revealed that
      multilinguals were more accurate than monolinguals and that both the multilingual
      and bilingual groups were more accurate than a control group that received no
      training. The results of the experiment not only suggest that multilinguals and
      bilinguals have enhanced speech perception abilities compared to monolinguals,
      but they also indicate that bi-/multilingualism helps develop superior learning
      abilities. This provides support for the idea that learning more than one
      language has positive effects on the cognitive development of an individual
      (e.g., Bialystok et al., 2004).

PMID- 23145628
TI  - Prevalence of absolute pitch: a comparison between Japanese and Polish music
      students.
AB  - Comparable large-scale surveys including an on-site pitch-naming test were
      conducted with music students in Japan and Poland to obtain more convincing
      estimates of the prevalence of absolute pitch (AP) and examine how musical
      experience relates to AP. Participants with accurate AP (95% correct
      identification) accounted for 30% of the Japanese music students, but only 7% of
      the Polish music students. This difference in the performance of pitch naming was
      related to the difference in musical experience. Participants with AP had begun
      music training at an earlier age (6 years or earlier), and the average year of
      commencement of musical training was more than 2 years earlier for the Japanese
      music students than for the Polish students. The percentage of participants who
      had received early piano lessons was 94% for the Japanese musically trained
      students but was 72% for the Polish music students. Approximately one-third of
      the Japanese musically trained students had attended the Yamaha Music School,
      where lessons on piano or electric organ were given to preschool children in
      parallel with fixed-do solfege singing training. Such early music instruction was
      not as common in Poland. The relationship of AP with early music training is
      discussed.

PMID- 23145629
TI  - Conformal scanning laser Doppler vibrometer measurement of tenor steelpan
      response to impulse excitation.
AB  - A conformal scanning laser Doppler vibrometer system is used in conjunction with
      a mechanical pannist to measure the surface normal vibration of the entire
      playing surface of a C-lead tenor steelpan. The mechanical pannist is a device
      designed to deliver controlled, repeatable strikes that mimic a mallet during
      authentic use. A description of the measurement system is followed by select
      examples of behavior common to the results from three different excitation notes.
      A summary of observed response shapes and associated frequencies demonstrates the
      concerted placement of note overtones by the craftsmen who manufacture and tune
      the instruments. The measurements provide a rich mechanical snapshot of the
      complex motion that generates the distinctive sound of a steelpan.

PMID- 23145630
TI  - The influence of pipe organ reed curvature on tone quality.
AB  - Although organ flue pipes have been widely studied, the same claim cannot be made
      for pipe organ reed stops. Given certain design constraints, such as the type of
      reed stop being voiced and the desired tone quality, the reed voicer must use
      consummate skill to curve the reed tongue so as to produce the best and most
      stable tone as well as to guarantee that each pipe blends with its neighbors. The
      amount and type of curve given to a reed tongue influences not only the harmonic
      structure of the steady-state sound but also the attack. There are two
      fundamentally different types of curvature that can be given to a reed tongue,
      the trompette (chorus reed) curve (which gives a bright sound) and the smooth
      toned curve employed for clarinet pipes. This study investigated the effect of
      reed curvature on the vibration and tone (as assessed by professionals) on reed
      tongues of both types. Two F2 (8'F, 87.3 Hz) pipes (a trompette and a clarinet)
      were constructed and voiced with differently curved tongues to produce a variety
      of tones. The vibration of the reed tongue was measured under typical conditions
      by laser vibrometer; the pressure waves in the boot and in the shallot were
      measured by means of one-quarter inch microphones, and the pipe's sound was
      recorded at the egress. By performing various measurements simultaneously, phase
      differences were also determined, the extreme sensitivity of tone to reed
      curvature was demonstrated, and a recently proposed theory of reed vibration was
      shown to be more accurate than the standard model.

PMID- 23145631
TI  - Acoustics of fish shelters: frequency response and gain properties.
AB  - Many teleosts emit sounds from cavities beneath stones and other types of
      submerged objects, yet the acoustical properties of fish shelters are virtually
      unexplored. This study examines the gain properties of shelters commonly used by
      Mediterranean gobies as hiding places and/or nest sites in the field (flat
      stones, shells belonging to five bivalve species), or within aquarium tanks
      (tunnel-shaped plastic covers, concrete blocks, concrete cylinder pipe, halves of
      terracotta flower pots). All shelters were acoustically stimulated using a small
      underwater buzzer, placed inside or around the shelter to mimic a fish calling
      from the nest site, and different types of driving stimuli (white noise, pure
      tones, and artificial pulse trains). Results showed the presence of significant
      amplitude gain (3-18 dB) at frequencies in the range 100-150 Hz in all types of
      natural shelters but one (Mytilus), terracotta flower pots, and concrete blocks.
      Gain was higher for stones and artificial shelters than for shells. Gain peak
      amplitude increased with the weight of stones and shells. Conclusions were
      verified by performing analogous acoustical tests on flat stones in the stream.
      Results draw attention to the use of suitable shelters for proper recording of
      sounds produced by fishes kept within laboratory aquaria.

PMID- 23145632
TI  - Temporary threshold shifts and recovery in a harbor porpoise (Phocoena phocoena)
      after octave-band noise at 4 kHz.
AB  - Safety criteria for underwater sound produced during offshore pile driving are
      needed to protect marine mammals. A harbor porpoise was exposed to fatiguing
      noise at 18 sound pressure level (SPL) and duration combinations. Its temporary
      hearing threshold shift (TTS) and hearing recovery were quantified with a
      psychoacoustic technique. Octave-band white noise centered at 4 kHz was the
      fatiguing stimulus at three mean received SPLs (124, 136, and 148 dB re 1 MUPa)
      and at six durations (7.5, 15, 30, 60, 120, and 240 min). Approximate received
      sound exposure levels (SELs) varied between 151 and 190 dB re 1 MUPa(2) s.
      Hearing thresholds were determined for a narrow-band frequency-swept sine wave
      (3.9-4.1 kHz; 1 s) before exposure to the fatiguing noise, and at 1-4, 4-8, 8-12,
      48, and 96 min after exposure. The lowest SEL (151 dB re 1 MUPa(2) s) which
      caused a significant TTS(1-4) was due to exposure to an SPL of 124 dB re 1 MUPa
      for 7.5 min. The maximum TTS(1-4), induced after a 240 min exposure to 148 dB re
      1 MUPa, was around 15 dB at a SEL of 190 dB re 1 MUPa(2) s. Recovery time
      following TTS varied between 4 min and under 96 min, depending on the exposure
      level, duration, and the TTS induced.

PMID- 23145633
TI  - Spatiotemporal evolution of cavitation dynamics exhibited by flowing microbubbles
      during ultrasound exposure.
AB  - Ultrasound and microbubble-based therapies utilize cavitation to generate
      bioeffects, yet cavitation dynamics during individual pulses and across
      consecutive pulses remain poorly understood under physiologically relevant flow
      conditions. SonoVue((r)) microbubbles were made to flow (fluid velocity: 10-40
      mm/s) through a vessel in a tissue-mimicking material and were exposed to
      ultrasound [frequency: 0.5 MHz, peak-rarefactional pressure (PRP): 150-1200 kPa,
      pulse length: 1-100,000 cycles, pulse repetition frequency (PRF): 1-50 Hz, number
      of pulses: 10-250]. Radiated emissions were captured on a linear array, and
      passive acoustic mapping was used to spatiotemporally resolve cavitation events.
      At low PRPs, stable cavitation was maintained throughout several pulses, thus
      generating a steady rise in energy with low upstream spatial bias within the
      focal volume. At high PRPs, inertial cavitation was concentrated in the first 6.3
      +/- 1.3 ms of a pulse, followed by an energy reduction and high upstream bias.
      Multiple pulses at PRFs below a flow-dependent critical rate (PRF(crit)) produced
      predictable and consistent cavitation dynamics. Above the PRF(crit), energy
      generated was unpredictable and spatially biased. In conclusion, key parameters
      in microbubble-seeded flow conditions were matched with specific types,
      magnitudes, distributions, and durations of cavitation; this may help in
      understanding empirically observed in vivo phenomena and guide future pulse
      sequence designs.

PMID- 23145634
TI  - The vocal repertoire of the Key Largo woodrat (Neotoma floridana smalli).
AB  - The Key Largo woodrat (Neotoma floridana smalli) is an endangered rodent endemic
      to the island of Key Largo, FL. There is little information on vocal
      communication in this species and descriptions of the acoustic structure of calls
      are lacking. A captive breeding program was established as part of the recovery
      plan for the species, providing the opportunity to investigate the vocal
      repertoire and acoustic structure of calls in both wild and captive contexts.
      Audio and video recordings were conducted at the Crocodile Lake National Wildlife
      Refuge in Key Largo and at Disney's Animal Kingdom((r)). Analysis of the acoustic
      structure of calls resulted in four provisional call types: "Tonal calls"
      consisted of "ultrasonic vocalizations" (40 kHz fundamental frequency, F(0)),
      "high squeaks" (10 kHz F(0)), and "squeaks" (1.8 kHz F(0)). "Noisy," broadband
      calls known as "raspy" vocalizations did not exhibit fundamental frequencies, but
      contained several prominent spectral peaks (from 9 to 40 kHz). The social
      contexts of vocal production showed that all four call types were associated with
      pup need or interactions between pups and dams, and that raspy vocalizations were
      associated with courtship and copulation. Adults without pups exhibited little or
      no vocal activity, which may result from solitary lifestyles and predator
      avoidance.

PMID- 23145635
TI  - In situ source levels of mulloway (Argyrosomus japonicus) calls.
AB  - Mulloway (Argyrosomus japonicus) in Mosman Bay, Western Australia produce three
      call categories associated with spawning behavior. The determination of call
      source levels and their contribution to overall recorded sound pressure levels is
      a significant step towards estimating numbers of calling fish within the
      detection range of a hydrophone. The source levels and ambient noise also provide
      significant information on the impacts anthropogenic activity may have on the
      detection of A. japonicus calls. An array of four hydrophones was deployed to
      record and locate individual fish from call arrival-time differences. Successive
      A. japonicus calls produced samples at various ranges between 1 and 100 m from
      one of the array hydrophones. The three-dimensional localization of calls,
      together with removal of ambient noise, allowed the determination of source
      levels for each call category using observed trends in propagation losses and
      interference. Mean source levels (at 1 m from the hydrophone) of the three call
      categories were calculated as 163 +/- 16 dB re 1 MUPa for Category 1 calls (short
      call of 2-5 pulses); 172 +/- 4 dB re 1 MUPa for Category 2 calls (long calls of
      11-32 pulses); and 157 +/- 5 dB re 1 MUPa for Category 3 calls (series of
      successive calls of 1-4 pulses, increasing in call rate).

PMID- 23145636
TI  - Temporal summation of airborne tones in a California sea lion (Zalophus
      californianus).
AB  - The trade-off between sound level and duration on hearing sensitivity (temporal
      summation) was investigated in a California sea lion (Zalophus californianus)
      using airborne pure-tone stimuli. Thresholds were behaviorally measured using the
      method of constant stimuli at 2.5, 5, and 10 kHz for nine signal durations
      ranging from 25 to 500 ms. In general, thresholds decreased as duration increased
      up to 300 ms, beyond which thresholds did not significantly improve. When these
      data were fitted separately to two versions of an exponential model, the
      estimated time constants (92-167 ms) were generally consistent between the two
      fits. However, the model with more free parameters generated fits with
      consistently higher R(2) values, while avoiding potential arbitrary decisions
      about which data to include. The time constants derived for the California sea
      lion were generally consistent with those reported for other mammals, including
      other pinnipeds. The current study did not show a clear correlation between time
      constant and test frequency. The results should be considered when conducting
      audiometric work, assessing communications ranges, and evaluating potential noise
      impacts of airborne tonal signals on California sea lions.

PMID- 23145694
TI  - Aspect-dependent radiated noise analysis of an underway autonomous underwater
      vehicle.
AB  - This paper presents an analysis of the acoustic emissions emitted by an underway
      REMUS-100 autonomous underwater vehicle (AUV) that were obtained near Honolulu
      Harbor, HI using a fixed, bottom-mounted horizontal line array (HLA). Spectral
      analysis, beamforming, and cross-correlation facilitate identification of
      independent sources of noise originating from the AUV. Fusion of navigational
      records from the AUV with acoustic data from the HLA allows for an aspect
      dependent presentation of calculated source levels of the strongest propulsion
      tone.

PMID- 23145637
TI  - Effects of encapsulation damping on the excitation threshold for subharmonic
      generation from contrast microbubbles.
AB  - A recent study [Katiyar and Sarkar (2011). J. Acoust. Soc. Am. 130, 3137-3147]
      showed that in contrast to the analytical result for free bubbles, the minimum
      threshold for subharmonic generation for contrast microbubbles does not
      necessarily occur at twice the resonance frequency. Here increased damping-either
      due to the small radius or the encapsulation-is shown to shift the minimum
      threshold away from twice the resonance frequency. Free bubbles as well as four
      models of the contrast agent encapsulation are investigated varying the surface
      dilatational viscosity. Encapsulation properties are determined using measured
      attenuation data for a commercial contrast agent. For sufficiently small damping,
      models predict two minima for the threshold curve-one at twice the resonance
      frequency being lower than the other at resonance frequency-in accord with the
      classical analytical result. However, increased damping damps the bubble response
      more at twice the resonance than at resonance, leading to a flattening of the
      threshold curve and a gradual shift of the absolute minimum from twice the
      resonance frequency toward the resonance frequency. The deviation from the
      classical result stems from the fact that the perturbation analysis employed to
      obtain it assumes small damping, not always applicable for contrast microbubbles.

PMID- 23145695
TI  - Effects of shapes and symmetries of scatterers on acoustic dual-negative
      refraction.
AB  - The potential operating conditions of acoustic dual-negative refraction (ADNR)
      are investigated by band structure theory for scatterers with different shapes
      and symmetries. Specifically, two types of lattices (triangular and honeycomb)
      and four different shapes of scatterers (circle, hexagon, square and triangle)
      are considered. Based on the generation mechanism of the ADNR effect, which is
      dependent on the frequency of the incident wave at the overlapping second and
      third Bloch bands, the optimum operating frequencies of ADNR with different
      crystal structures are given. The calculations demonstrate that the ADNR effect
      can be generated at the normalized frequency from 0.8 to 1.05.

PMID- 23145696
TI  - A three-dimensional parabolic equation model of sound propagation using higher
      order operator splitting and Pade approximants.
AB  - An alternating direction implicit (ADI) three-dimensional fluid parabolic
      equation solution method with enhanced accuracy is presented. The method uses a
      square-root Helmholtz operator splitting algorithm that retains cross-multiplied
      operator terms that have been previously neglected. With these higher-order cross
      terms, the valid angular range of the parabolic equation solution is improved.
      The method is tested for accuracy against an image solution in an idealized wedge
      problem. Computational efficiency improvements resulting from the ADI
      discretization are also discussed.

PMID- 23145697
TI  - Is clear speech tailored to counter the effect of specific adverse listening
      conditions?
AB  - The study investigated the perception of speech produced to counter the effects
      of adverse listening conditions. Participants completed a problem-solving task
      with an interlocutor in good listening conditions (NB) or with the interlocutor
      hearing them via a vocoder (VOC) or babble (BAB). Keywords extracted from
      recordings were presented in babble for initial consonant identification. BAB
      tokens were identified faster than VOC or NB tokens even though VOC and BAB
      tokens were rated as similarly clear. Acoustic measures showed clarifications to
      be global rather than specifically enhancing phonological contrasts. These
      results suggest that clear speaking styles are tailored to listeners' needs.

PMID- 23145698
TI  - Effects of low harmonics on tone identification in natural and vocoded speech.
AB  - This study investigated the contribution of low-frequency harmonics to
      identifying Mandarin tones in natural and vocoded speech in quiet and noisy
      conditions. Results showed that low-frequency harmonics of natural speech led to
      highly accurate tone identification; however, for vocoded speech, low-frequency
      harmonics yielded lower tone identification than stimuli with full harmonics,
      except for tone 4. Analysis of the correlation between tone accuracy and the
      amplitude-F0 correlation index suggested that "more" speech contents (i.e., more
      harmonics) did not necessarily yield better tone recognition for vocoded speech,
      especially when the amplitude contour of the signals did not co-vary with the F0
      contour.

PMID- 23145699
TI  - Selective attention in an overcrowded auditory scene: implications for auditory
      based brain-computer interface design.
AB  - Listeners are good at attending to one auditory stream in a crowded environment.
      However, is there an upper limit of streams present in an auditory scene at which
      this selective attention breaks down? Here, participants were asked to attend one
      stream of spoken letters amidst other letter streams. In half of the trials, an
      initial primer was played, cueing subjects to the sound configuration. Results
      indicate that performance increases with token repetitions. Priming provided a
      performance benefit, suggesting that stream selection, not formation, is the
      bottleneck associated with attention in an overcrowded scene. Results'
      implications for brain-computer interfaces are discussed.

PMID- 23145700
TI  - English sentence recognition in speech-shaped noise and multi-talker babble for
      English-, Chinese-, and Korean-native listeners.
AB  - This study aimed to investigate English sentence recognition in quiet and two
      types of maskers, multi-talker babble (MTB) and long-term speech-shaped noise
      (LTSSN), with varied signal-to-noise ratios, for English-, Chinese-, and Korean
      native listeners. Results showed that first, sentence recognition for non-native
      listeners was affected more by background noise than that for native listeners;
      second, the masking effects of LTSSN were similar between Chinese and Korean
      listeners, but the masking effects of MTB were greater for Chinese than for
      Korean listeners, suggesting possible interaction effects between the non-native
      listener's native language and speech-like competing noise in sentence
      recognition.

PMID- 23145701
TI  - Pitch strength of noise-vocoded harmonic tone complexes in normal-hearing
      listeners.
AB  - To study the role of harmonic structure in pitch perception, normal-hearing
      listeners were tested using noise-vocoded harmonic tone complexes. When tested in
      a magnitude judgment procedure using vocoded versions generated with 2-128
      channels, judgments of pitch strength increased systematically as the number of
      channels increased and reflected acoustic cues based on harmonic peak-to-valley
      ratio, but not cues based on periodicity strength. When tested in a fundamental
      frequency discrimination task, listeners correctly recognized the direction of
      pitch change with as few as eight noise-vocoded channels. The results suggest
      that spectral processing contributes substantially to pitch perception in normal
      hearing listeners.

PMID- 23145702
TI  - Real time automatic detection of bearing fault in induction machine using
      kurtogram analysis.
AB  - A proposed signal processing technique for incipient real time bearing fault
      detection based on kurtogram analysis is presented in this paper. The kurtogram
      is a fourth-order spectral analysis tool introduced for detecting and
      characterizing non-stationarities in a signal. This technique starts from
      investigating the resonance signatures over selected frequency bands to extract
      the representative features. The traditional spectral analysis is not appropriate
      for non-stationary vibration signal and for real time diagnosis. The performance
      of the proposed technique is examined by a series of experimental tests
      corresponding to different bearing conditions. Test results show that this signal
      processing technique is an effective bearing fault automatic detection method and
      gives a good basis for an integrated induction machine condition monitor.

PMID- 23145703
TI  - Hybrid phononic crystals for broad-band frequency noise control by sound blocking
      and localization.
AB  - A bandgap cannot be enlarged sufficiently enough to suppress a broad-band noise
      only with a single type of finite-length phononic crystals. Here, a hybrid
      phononic crystal consisting of a bi-prism and an inverted bi-prism is proposed
      for noise control in a broad band; a stop band is formed in a central frequency
      range while positive-positive and positive-negative refractions occur in lower
      and higher frequency ranges to concentrate acoustic energy in a central localized
      zone. Thereby, the remaining zone becomes little affected by the noise. Analysis
      and numerical simulations are given for the justification of the proposed
      configuration.

PMID- 23145704
TI  - Vocalization of echolocation-like pulses for interindividual interaction in
      horseshoe bats (Rhinolophus ferrumequinum).
AB  - Although much is known about the echolocation of horseshoe bats (Rhinolophus
      spp.), little is known about the characteristics and function of their
      communication calls. This study focused on a stereotyped behavior of a bat
      approaching a companion animal in the colony, and examined their interaction and
      vocalization during this behavior. The bats emit echolocation-like vocalizations
      when approaching each other and these vocalizations contain a "buildup" pulse
      sequence, in which the frequency of the pulse increases gradually to normal
      echolocation pulse frequencies. The results suggest that the echolocation-like
      pulses serve an important role in communication within the colony.

PMID- 23145705
TI  - Mapping cumulative noise from shipping to inform marine spatial planning.
AB  - Including ocean noise in marine spatial planning requires predictions of noise
      levels on large spatiotemporal scales. Based on a simple sound transmission model
      and ship track data (Automatic Identification System, AIS), cumulative underwater
      acoustic energy from shipping was mapped throughout 2008 in the west Canadian
      Exclusive Economic Zone, showing high noise levels in critical habitats for
      endangered resident killer whales, exceeding limits of "good conservation status"
      under the EU Marine Strategy Framework Directive. Error analysis proved that
      rough calculations of noise occurrence and propagation can form a basis for
      management processes, because spending resources on unnecessary detail is
      wasteful and delays remedial action.

PMID- 23145706
TI  - Channel interaction limits melodic pitch perception in simulated cochlear
      implants.
AB  - In cochlear implants (CIs), melodic pitch perception is limited by the spectral
      resolution, which in turn is limited by the number of spectral channels as well
      as interactions between adjacent channels. This study investigated the effect of
      channel interaction on melodic contour identification (MCI) in normal-hearing
      subjects listening to novel 16-channel sinewave vocoders that simulated channel
      interaction in CI signal processing. MCI performance worsened as the degree of
      channel interaction increased. Although greater numbers of spectral channels may
      be beneficial to melodic pitch perception, the present data suggest that it is
      also important to improve independence among spectral channels.

PMID- 23145707
TI  - Temporal resolution analysis in frequency domain linear prediction.
AB  - Frequency domain linear prediction (FDLP) is a technique for auto-regressive
      modeling of Hilbert envelopes. In this letter, the resolution properties of the
      FDLP model are investigated using synthetic signals with impulses immersed in
      noise. The effect of various factors are studied which affect the temporal
      resolution and this analysis suggests ways to improve the resolution of the FDLP
      envelopes in noisy speech. The high resolution FDLP envelopes are used to derive
      robust features for phoneme recognition in noisy and reverberant speech. In these
      experiments, the FDLP features derived from high resolution envelopes provide
      significant improvements.

PMID- 23145708
TI  - Communication: Application of state-specific multireference coupled cluster
      methods to core-level excitations.
AB  - The concept of the model space underlying multireference coupled-cluster (MRCC)
      formulations is a powerful tool to deal with complex correlation effects for
      various electronic states. Here, we demonstrate that iterative state-specific
      MRCC methods (SS-MRCC) based on properly defined model spaces can be used to
      describe core-level excited states even when Hartree-Fock orbitals are utilized.
      We show that the SS-MRCC models with single and double excitations are comparable
      in accuracy to high-level single reference equation-of-motion coupled cluster
      (EOMCC) formalism.

PMID- 23145709
TI  - Communication: An exact bound on the bridge function in integral equation
      theories.
AB  - We show that the formal solution of the general closure relation occurring in
      Ornstein-Zernike-type integral equation theories in terms of the Lambert W
      function leads to an exact relation between the bridge function and correlation
      functions, most notably to an inequality that bounds possible bridge values. The
      analytical results are illustrated on the example of the Lennard-Jones fluid for
      which the exact bridge function is known from computer simulations under various
      conditions. The inequality has consequences for the development of bridge
      function models and rationalizes numerical convergence issues.

PMID- 23145710
TI  - Communication: An unusual halogen-bonding motif: the LiBr...BrF dimer as a model
      system.
AB  - A stable complex, LiBr...BrF, is predicted in which the negative Br atom of LiBr
      is anchored to the Br atom of BrF by a halogen bond, while the positively charged
      Li atom interacts with the lone pair electron density on the Br atom of BrF in a
      direction roughly perpendicular to the halogen bond. As far as we are aware, this
      is the first reported instance of an atom of one diatomic molecule (Br of BrF)
      being bonded to two different, oppositely charged atoms (Li and Br) of another
      diatomic molecule (LiBr). Other less stable dimers of LiBr and BrF were predicted
      and compared with this novel complex.

PMID- 23145711
TI  - Rectified brownian transport in corrugated channels: Fractional brownian motion
      and Levy flights.
AB  - We study fractional brownian motion and Levy flights in periodic corrugated
      channels without any external driving forces. From numerical simulations, we find
      that both fractional gaussian noise and Levy-stable noise in asymmetric
      corrugated channels can break thermodynamical equilibrium and induce directed
      transport. The rectified mechanisms for fractional brownian motion and Levy
      flights are different. The former is caused by non-uniform spectral distribution
      (low or high frequencies) of fractional gaussian noise, while the latter is due
      to the nonthermal character (occasional long jumps) of the Levy-stable noise. For
      fractional brownian motion, average velocity increases with the Hurst exponent
      for the persistent case, while for the antipersistent case there exists an
      optimal value of Hurst exponent at which average velocity takes its maximal
      value. For Levy flights, the group velocity decreases monotonically as the Levy
      index increases. In addition, for both cases, the optimized periodicity and
      radius at the bottleneck can facilitate the directed transport. Our results could
      be implemented in constrained structures with narrow channels and pores where the
      particles undergo anomalous diffusion.

PMID- 23145712
TI  - The equation-of-motion coupled cluster method for triple electron attached
      states.
AB  - The initial implementation of the triple electron attachment (TEA) equation-of
      motion (EOM) coupled cluster (CC) method is presented, aiming at the description
      of electronic states with three open shell electrons outside a suitably chosen
      closed shell vacuum. In particular, such an approach can be used for describing
      dissociation of chemical bonds predominantly formed by three valence electrons,
      for example, in LiC and NaC molecules. Both ground and excited states are
      considered while rigorously maintaining the correct spin value. The preliminary
      results show a correct asymptotic behavior of the dissociation curves. At the
      same time, we emphasize that a chemically accurate description will require an
      extension of the minimal TEA-EOM-CC model introduced here, analogous to those
      already used in the double ionization potential and double electron attachment
      methods.

PMID- 23145713
TI  - Diffusion in two-dimensional conical varying width channels: comparison of
      analytical and numerical results.
AB  - This study is devoted to the unbiased motion of a point-like brownian particle in
      two-dimensional tilted asymmetric channels of varying width formed by straight
      walls. An effective one-dimensional description in terms of the generalized Fick
      Jacobs equation is used to derive formulas that yield the particle's effective
      diffusion coefficient as a function of the geometric parameters of the channel.
      To such end, we use the formulas obtained by Bradley [Phys. Rev. E 80, 061142
      (2009)] and by Dagdug and Pineda [J. Chem. Phys. 137, 024107 (2012)] to study two
      dimensional diffusion in narrow and smoothly asymmetric channels of varying
      width. Comparison with brownian dynamics simulation results allows us to
      establish the domain of applicability of both the one-dimensional description and
      the effective diffusion coefficient formulas.

PMID- 23145714
TI  - Embedded fragmentation of vibrational energies.
AB  - Can the zero-point vibrational energies (ZPVE) of molecular clusters and crystals
      be evaluated as sums of ZPVE of constituent molecular fragments embedded in the
      cluster or crystal electrostatic environment? What is the appropriate unit of
      fragmentation: monomers or overlapping dimers? Can the contributions of acoustic
      phonons, which are fundamentally delocalized, be recuperated at satisfactory
      accuracy? These questions are answered by this study applying embedded monomer-
      and dimer-fragmentation methods to the harmonic ZPVE of hydrogen fluoride
      clusters, hydrogen fluoride crystal, and water clusters. Our findings are as
      follows: (1) ZPVE are reproduced accurately by both fragmentation schemes within
      a few percents of exact values or a few tenths of 1 kcal mol(-1) per molecule
      even for crystalline hydrogen fluoride, which has acoustic phonons. (2) Both the
      monomer- and dimer-based fragmentation are nearly equally accurate and useful for
      the absolute values of ZPVE, but the latter is more reliable than the former in
      reproducing the relative ZPVE of cluster isomers of the same size. (3) The
      embedding field is essential as it renders nonzero frequencies to the
      translational and rotational motions of monomers and dimers, accounting for the
      pseudo-translational and librational motions of the entire clusters or crystals.
      (4) Some of these low-frequency modes of fragments are calculated to have
      imaginary frequencies because the fragments are not at their equilibrium
      geometries, causing ZPVE to be complex. The imaginary part of ZPVE, which is
      nonphysical and is guaranteed to vanish in the exact limit of the many-body
      expansion, is nonetheless a useful estimate of errors in the real part.

PMID- 23145715
TI  - Exact two-component relativistic theory for NMR parameters: general formulation
      and pilot application.
AB  - The previously proposed exact two-component (X2C) relativistic theory of nuclear
      magnetic resonance (NMR) parameters [Q. Sun, W. Liu, Y. Xiao, and L. Cheng, J.
      Chem. Phys. 131, 081101 (2009)] is reformulated to accommodate two schemes for
      kinetic balance, five schemes for magnetic balance, and three schemes for
      decoupling in a unified manner, at both matrix and operator levels. In addition,
      three definitions of spin magnetization are considered in the coupled-perturbed
      Kohn-Sham equation. Apart from its simplicity, the most salient feature of X2C
      NMR lies in that its diamagnetic and paramagnetic terms agree individually with
      the corresponding four-component counterparts for any finite basis. For practical
      applications, five approximate schemes for the first order coupling matrix X(10)
      and four approximate schemes for the treatment of two-electron integrals are
      introduced, which render the computations of X2C-NMR very much the same as those
      of approximate two-component approaches.

PMID- 23145716
TI  - Prediction of organic molecular crystal geometries from MP2-level fragment
      quantum mechanical/molecular mechanical calculations.
AB  - The fragment-based hybrid many-body interaction (HMBI) model provides a
      computationally affordable means of applying electronic structure wavefunction
      methods to molecular crystals. It combines a quantum mechanical treatment of
      individual molecules in the unit cell and their short-range pairwise interactions
      with a polarizable molecular mechanics force-field treatment of long-range and
      many-body interactions. Here, we report the implementation of analytic nuclear
      gradients for the periodic model to enable full relaxation of both the atomic
      positions and crystal lattice parameters. Using a set of five, chemically diverse
      molecular crystals, we compare the quality of the HMBI MP2/aug-cc-pVDZ-level
      structures with those obtained from dispersion-corrected periodic density
      functional theory, B3LYP-D*, and from the Amoeba polarizable force field. The MP2
      level structures largely agree with the experimental lattice parameters to within
      2%, and the root-mean-square deviations in the atomic coordinates are less than
      0.2 A. These MP2 structures are almost as good as those predicted from periodic
      B3LYP-D*/TZP and are significantly better than those obtained with B3LYP-D*/6
      31G(d,p) or with the Amoeba force field.

PMID- 23145717
TI  - Development and application of a particle-particle particle-mesh Ewald method for
      dispersion interactions.
AB  - For inhomogeneous systems with interfaces, the inclusion of long-range dispersion
      interactions is necessary to achieve consistency between molecular simulation
      calculations and experimental results. For accurate and efficient incorporation
      of these contributions, we have implemented a particle-particle particle-mesh
      Ewald solver for dispersion (r(-6)) interactions into the LAMMPS molecular
      dynamics package. We demonstrate that the solver's O(N log N) scaling behavior
      allows its application to large-scale simulations. We carefully determine a set
      of parameters for the solver that provides accurate results and efficient
      computation. We perform a series of simulations with Lennard-Jones particles,
      SPC/E water, and hexane to show that with our choice of parameters the dependence
      of physical results on the chosen cutoff radius is removed. Physical results and
      computation time of these simulations are compared to results obtained using
      either a plain cutoff or a traditional Ewald sum for dispersion.

PMID- 23145718
TI  - Solving the vibrational Schrodinger equation using bases pruned to include
      strongly coupled functions and compatible quadratures.
AB  - In this paper, we present new basis pruning schemes and compatible quadrature
      grids for solving the vibrational Schrodinger equation. The new basis is designed
      to include the product basis functions coupled by the largest terms in the
      potential and important for computing low-lying vibrational levels. To solve the
      vibrational Schrodinger equation without approximating the potential, one must
      use quadrature to compute potential matrix elements. For a molecule with more
      than five atoms, the use of iterative methods is imperative, due to the size of
      the basis and the quadrature grid. When using iterative methods in conjunction
      with quadrature, it is important to evaluate matrix-vector products by doing sums
      sequentially. This is only possible if both the basis and the grid have
      structure. Although it is designed to include only functions coupled by the
      largest terms in the potential, the new basis and also the quadrature for doing
      integrals with the basis have enough structure to make efficient matrix-vector
      products possible. When results obtained with a multimode approximation to the
      potential are accurate enough, full-dimensional quadrature is not necessary.
      Using the quadrature methods of this paper, we evaluate the accuracy of
      calculations made by making multimode approximations.

PMID- 23145719
TI  - The fundamental role of quantized vibrations in coherent light harvesting by
      cryptophyte algae.
AB  - The influence of fast vibrations on energy transfer and conversion in natural
      molecular aggregates is an issue of central interest. This article shows the
      important role of high-energy quantized vibrations and their non-equilibrium
      dynamics for energy transfer in photosynthetic systems with highly localized
      excitonic states. We consider the cryptophyte antennae protein phycoerythrin 545
      and show that coupling to quantized vibrations, which are quasi-resonant with
      excitonic transitions is fundamental for biological function as it generates non
      cascaded transport with rapid and wider spatial distribution of excitation
      energy. Our work also indicates that the non-equilibrium dynamics of such
      vibrations can manifest itself in ultrafast beating of both excitonic populations
      and coherences at room temperature, with time scales in agreement with those
      reported in experiments. Moreover, we show that mechanisms supporting coherent
      excitonic dynamics assist coupling to selected modes that channel energy to
      preferential sites in the complex. We therefore argue that, in the presence of
      strong coupling between electronic excitations and quantized vibrations, a
      concrete and important advantage of quantum coherent dynamics is precisely to
      tune resonances that promote fast and effective energy distribution.

PMID- 23145720
TI  - Analytical estimates of free brownian diffusion times in corrugated narrow
      channels.
AB  - The diffusion of a suspended brownian particle along a sinusoidally corrugated
      narrow channel is investigated to assess the validity of two competing analytical
      schemes, both based on effective one-dimensional kinetic equations, one
      continuous (entropic channel scheme) and the other discrete (random walker
      scheme). For narrow pores, the characteristic diffusion time scale is represented
      by the mean first exit time out of a channel compartment. Such a diffusion time
      has been analytically calculated in both approximate schemes; the two analytical
      results coincide in leading order and are in excellent agreement with the
      simulation data.

PMID- 23145721
TI  - Efficient energy transfer in light-harvesting systems: quantum-classical
      comparison, flux network, and robustness analysis.
AB  - Following the calculation of optimal energy transfer in thermal environment in
      our first paper [J. L. Wu, F. Liu, Y. Shen, J. S. Cao, and R. J. Silbey, New J.
      Phys. 12, 105012 (2010)], full quantum dynamics and leading-order "classical"
      hopping kinetics are compared in the seven-site Fenna-Matthews-Olson (FMO)
      protein complex. The difference between these two dynamic descriptions is due to
      higher-order quantum corrections. Two thermal bath models, classical white noise
      (the Haken-Strobl-Reineker (HSR) model) and quantum Debye model, are considered.
      In the seven-site FMO model, we observe that higher-order corrections lead to
      negligible changes in the trapping time or in energy transfer efficiency around
      the optimal and physiological conditions (2% in the HSR model and 0.1% in the
      quantum Debye model for the initial site at BChl 1). However, using the concept
      of integrated flux, we can identify significant differences in branching
      probabilities of the energy transfer network between hopping kinetics and quantum
      dynamics (26% in the HSR model and 32% in the quantum Debye model for the initial
      site at BChl 1). This observation indicates that the quantum coherence can
      significantly change the distribution of energy transfer pathways in the flux
      network with the efficiency nearly the same. The quantum-classical comparison of
      the average trapping time with the removal of the bottleneck site, BChl 4,
      demonstrates the robustness of the efficient energy transfer by the mechanism of
      multi-site quantum coherence. To reconcile with the latest eight-site FMO model
      which is also investigated in the third paper [J. Moix, J. L. Wu, P. F. Huo, D.
      F. Coker, and J. S. Cao, J. Phys. Chem. Lett. 2, 3045 (2011)], the quantum
      classical comparison with the flux network analysis is summarized in Appendix C.
      The eight-site FMO model yields similar trapping time and network structure as
      the seven-site FMO model but leads to a more disperse distribution of energy
      transfer pathways.

PMID- 23145722
TI  - Extension of the source-sink potential (SSP) approach to multichannel quantum
      transport.
AB  - We present an extension of the single channel source-sink potential approach [F.
      Goyer, M. Ernzerhof, and M. Zhuang, J. Chem. Phys. 126, 144104 (2007)] for
      molecular electronic devices (MEDs) to multiple channels. The proposed
      multichannel source-sink potential method relies on an eigenchannel description
      of conducting states of the MED which are obtained by a self-consistent
      algorithm. We use the newly developed model to examine the transport of the 1
      phenyl-1,3-butadiene molecule connected to two coupled rows of atoms that act as
      contacts on the left and right sides. With an eigenchannel description of the
      wave function in the contacts, we determined that one of the eigenchannels is
      effectively closed by the interference effects of the side chain. Furthermore, we
      provide an example where we observe a complete inversion (from bonding to
      antibonding and vice versa) of the transverse character of the wave function upon
      passage through the molecule.

PMID- 23145723
TI  - An eight-dimensional quantum mechanical Hamiltonian for X + YCZ3 system and its
      applications to H + CH4 reaction.
AB  - An eight-dimensional quantum mechanical Hamiltonian has been proposed based on
      Palma and Clary's model in which the non-reacting CZ(3) group keeps a C(3v)
      symmetry in the X + YCZ(3) <-> XY + CZ(3) reaction J. Palma and D. C. Clary [J.
      Chem. Phys. 112, 1859 (2000)]. By transforming the original cartesian coordinate
      system (x, s) into a scaled polar coordinate system (q, gamma), the vibrational
      Hamiltonian of CZ(3) group is expressed in a simple form with a clear physical
      picture. This Hamiltonian is used to investigate the H + CH(4) -> H(2) + CH(3)
      reaction on the Jordan-Gilbert potential energy surface. The total reaction
      probabilities are calculated for the initial ground state, and umbrella, bending,
      symmetric, and asymmetric stretching excited states of CH(4) with total angular
      momentum J = 0. The integral cross sections for the reaction are also studied for
      these initial vibrational states with a centrifugal-sudden approximation. The
      total integral cross sections for the asymmetric stretching vibrational excited
      state are in good agreement with the experimental observations. The results also
      showed the difference of dynamical behavior between reactions from symmetric and
      asymmetric stretching excited states. The thermal rate constants are calculated
      for the temperature range T = 250-2000 K and compared with the experimental and
      other theoretical results.

PMID- 23145724
TI  - Interferometric background reduction for femtosecond stimulated Raman scattering
      loss spectroscopy.
AB  - We present a purely optical method for background suppression in nonlinear
      spectroscopy based on linear interferometry. Employing an unbalanced Sagnac
      interferometer, an unprecedented background reduction of 17  dB over a broad
      bandwidth of 60  THz (2000  cm(-1)) is achieved and its application to
      femtosecond stimulated Raman scattering loss spectroscopy is demonstrated. Apart
      from raising the signal-to-background ratio in the measurement of the Raman
      intensity spectrum, this interferometric method grants access to the spectral
      phase of the resonant chi(3) contribution. The spectral phase becomes apparent as
      a dispersive lineshape and is reproduced numerically with a simple oscillator
      model.

PMID- 23145725
TI  - Control of resonance enhanced multi-photon ionization photoelectron spectroscopy
      by phase-shaped femtosecond laser pulse.
AB  - In this paper, we theoretically demonstrate that the (2+1+1) resonance enhanced
      multi-photon ionization photoelectron spectroscopy in sodium atom can be
      effectively controlled by shaping femtosecond laser pulse with a pi phase step
      modulation in weak laser field, involving its total photoelectron energy, maximal
      photoelectron intensity, and spectroscopic bandwidth. Our results show that the
      total photoelectron energy can be suppressed but not enhanced, the maximal
      photoelectron intensity can be enhanced and also suppressed, and the
      photoelectron spectroscopy can be tremendously narrowed. These theoretical
      results can provide a feasible scheme to achieve the high-resolution
      photoelectron spectroscopy and study the excited state structure in atomic and
      molecular systems.

PMID- 23145726
TI  - Distortion of ethyne on formation of a pi complex with silver chloride: C2H2?Ag
      Cl characterised by rotational spectroscopy and ab initio calculations.
AB  - C(2)H(2)?Ag-Cl was formed from ethyne and AgCl in the gas phase and its
      rotational spectrum observed by both the chirped-pulse and Fabry-Perot cavity
      versions of Fourier-transform microwave spectroscopy. Reaction of laser-ablated
      silver metal with CCl(4) gave AgCl which then reacted with ethyne to give the
      complex. Ground-state rotational spectra of the six isotopologues
      (12)C(2)H(2)?(107)Ag(35)Cl, (12)C(2)H(2)?(109)Ag(35)Cl,
      (12)C(2)H(2)?(107)Ag(37)Cl, (12)C(2)H(2)?(109)Ag(37)Cl,
      (13)C(2)H(2)?(107)Ag(35)Cl, and (13)C(2)H(2)?(109)Ag(35)Cl were analysed to yield
      rotational constants A(0), B(0), and C(0), centrifugal distortion constants
      Delta(J), Delta(JK), and delta(J), and Cl nuclear quadrupole coupling constants
      chi(aa)(Cl) and chi(bb)(Cl)-chi(cc)(Cl). A less complete analysis was possible
      for (12)C(2)D(2)?(107)Ag(35)Cl and (12)C(2)D(2)?(109)Ag(35)Cl. Observed principal
      moments of inertia were interpreted in terms of a planar, T-shaped geometry of
      C(2v) symmetry in which the AgCl molecule lies along a C(2) axis of ethyne and
      the Ag atom forms a bond to the midpoint (*) of the ethyne pi bond. r(0) and
      r(m)(1) geometries and an almost complete r(s)-geometry were established. The
      ethyne molecule distorts on complex formation by lengthening of the C=C bond and
      movement of the two H atoms away from the C=C internuclear line and the Ag atom.
      The r(m)(1) bond lengths and angles are as follows: r(*?Ag) = 2.1800(3) A, r(C-C)
      = 1.2220(20) A, r(Ag-Cl) = 2.2658(3) A and the angle H-C=* has the value
      187.79(1) degrees . Ab initio calculations at the coupled-cluster singles and
      doubles level of theory with a perturbative treatment of triples (F12*)/cc-pVTZ
      yield a r(e) geometry in excellent agreement with the experimental r(m)(1)
      version, including the ethyne angular distortion.

PMID- 23145727
TI  - Rotational spectroscopic study of hydrogen cyanide embedded in small 4He
      clusters.
AB  - High resolution microwave spectra of the a-type, J = 1-0, transitions of He(N = 1
      6)-H(12)C(14)N, He(N = 1-6)-H(13)C(14)N, He(N = 1-6)-H(12)C(15)N, He(N = 1-7)
      D(12)C(14)N, and He(N = 1-6)-D(13)C(14)N clusters produced in a supersonic jet
      expansion were measured and analyzed. The resulting effective rotational
      constants, B(eff), initially decrease with the number of the attached helium
      atoms before reaching a minimum at N = 3 helium atoms for all isotopologues. The
      subsequent increase in B(eff) for N >= 4 is indicative of the onset of
      microscopic superfluidity. Comparison of our experimental B(eff) constants with
      those from quantum Monte Carlo simulations [A. A. Mikosz, J. A. Ramilowski, and
      D. Farrelly, J. Chem. Phys. 125, 014312 (2006)] reveals a nearly congruent trend
      in B(eff) for N up to 6. Analysis of the hyperfine structure of the (14)N
      containing isotopologues yielded a gradual incremental increase in the magnitude
      of chi(aa) and <P(2)(cos theta)> for N = 1-6, which suggests the internal
      rotation of the HCN molecule is becoming increasingly hindered.

PMID- 23145728
TI  - 1,1-Diamino-2,2-dinitroethylene under high pressure-temperature.
AB  - The structural phase stability of 1,1-diamino-2,2-dinitroethylene (FOX-7) has
      been studied up to 10 GPa through isothermal compression at 100  degrees C and
      200  degrees C using synchrotron mid- and far-infrared spectroscopy. During
      isothermal compression at 100  degrees C changes are observed in vibrational
      spectra with increase in pressure that are indicative of significant distortion
      to monoclinic alpha phase or a possible structural transformation to a high
      pressure alpha(') phase at 2.2 GPa and alpha(") phase at 6.1 GPa. At 200  degrees
      C, for the far- and mid-IR regimes, the similar changes were observed at 2.1
      (2.0) GPa and 5.3 (5.5) GPa, respectively. The observed change is nearly
      isobaric, consistent with previously reported high pressure and room temperature
      values, up to the highest temperature of 200  degrees C reached in our
      experiments. Over the total P-T range investigated, up to ~10 GPa and 200 
      degrees C, we observed no evidence of sample decomposition. The observed changes
      are partially reversible with only slight evidence of the high pressure
      distortion remaining upon complete decompression. Additional isobaric heating at
      1.07 GPa was performed in the mid-IR regime, which clearly revealed an onset of
      decomposition at 360  degrees C. Further x-ray or neutron diffraction, which are
      needed to fully resolve the cause of observed changes above 2 and 5 GPa, are
      ongoing.

PMID- 23145729
TI  - The Jahn-Teller effect in the electron momentum spectroscopy of ammonia.
AB  - The 1e and 3a(1) bands of the ammonia molecule have been studied using the high
      resolution electron momentum spectroscopy at impact energies of 1200 and 600 eV.
      Several slices of 1e and 3a(1) bands in the different binding energy ranges were
      selected, and their electron-momentum distributions were carefully compared. The
      discernable difference among the distributions of the selected slices of the 1e
      band shows that the Jahn-Teller effect indeed influences the electron momentum
      distribution of the 1e orbital of ammonia.

PMID- 23145730
TI  - The isotope dependence of dissociative recombination via the indirect mechanism.
AB  - A recently derived analytic formula for the low-energy dissociative recombination
      of molecular ions and electrons involving capture into vibrationally excited
      Rydberg states provides a simple expression for the isotope dependence of the
      process. This expression depends only on the ratio of the relevant vibrational
      frequencies of the two isotopomers of interest and can therefore be evaluated
      even without knowledge of the dynamical parameters required to determine the
      recombination cross sections. The expression is used to predict the isotope
      dependence for a number of molecular ions and the results are compared with
      experiment. While the agreement with the experiment is generally quite
      reasonable, discrepancies may indicate a breakdown of the assumptions used to
      derive the cross section formula or potential inaccuracies in the experiments.

PMID- 23145731
TI  - Towards understanding the nature of the intensities of overtone vibrational
      transitions.
AB  - The overtone vibrational transitions, i.e., transitions between states separated
      by more than one vibrational quantum play important role in many fields of
      physics and chemistry. The overtone transition is a purely quantum process
      associated with the so-called dynamical tunneling [Heller, E. J., "The many faces
      of tunneling," J. Phys. Chem. A 103(49), 10433-10444 (1999)] whose probability is
      small as compared to the fundamental transition. The transition probability is
      proportional to the Landau-Lifshitz tunneling factor similar to the Gamov factor
      in nuclear physics. However, as opposed to the Gamov tunneling, the Landau
      Lifshitz tunneling lacks any barrier to tunnel through: Its probability looks as
      if the system were forced to "dive" under the barrier up to a point where the
      transition can be performed without any change in momentum, hence with a high
      probability, and then to "emerge back" in a new state. It follows that the
      transition probability is associated with the shape of the potential in the
      classically forbidden region in the same sense as the transition energy is
      associated with the shape of the potential in the classically allowed region, as
      implied by the Bohr-Sommerfeld quantization rule, and in the same sense as the
      probability of the Gamov tunneling is associated with the shape of the potential
      within the barrier region. As soon as the tunneling character of the transition
      is recognized, the well-known extreme sensitivity of the overtone intensities to
      small variations of the fitting function representing the molecular potential
      [Lehmann, K. K. and Smith, A. M., "Where does overtone intensity come from?" J.
      Chem. Phys. 93(9), 6140-6147 (1990)] becomes fully understood: Small variations
      of the potential in the classical region, which do not affect the energy levels
      significantly, cause large variations in the forbidden region and hence do affect
      the tunneling factor. This dictates a clear strategy of constructing the
      potential energy and dipole moment functions (PEF and DMF) capable of explaining
      the data of vibrational spectroscopy and possessing a predictive power. In this
      paper, we will show that, for stretching vibrations, knowledge of the inner wall
      of the PEF is necessary to perform this task. Incorrect behavior of the PEF at
      extremely small interatomic separations corresponding to energies well above the
      dissociation limit results in an incorrect rate of the intensity falloff, hence a
      rapid increase of discrepancies between the calculated and observed intensities
      with overtone number. Analysis of experimental data on some di- and polyatomic
      molecules and their interpretations is presented, which shows that neglecting the
      tunneling nature of overtone transitions does not permit making predictions of
      the intensities with a known uncertainty. A new approach has to be developed.
      First of all, an ab initio PEF giving correct energy levels and having correct
      behavior of the repulsive wall must be constructed; thereafter, an ab initio DMF
      is invoked to explain the experimental data for lower (observed) transitions and
      to predict the intensities of higher (not yet observed) transitions with
      approximately the same accuracy as that for lower overtones. These ideas also
      apply to radiationless deactivation of rare-earth and transition-metal ions in
      laser media, which proceeds via overtone absorption of electronic energy by
      medium local vibrations.

PMID- 23145732
TI  - Sign preference in ion-induced nucleation: contributions to the free energy
      barrier.
AB  - We have performed a series of computer simulations using the AVUS-HR approach to
      better understand the origin of the sign preference in ion-induced nucleation. In
      particular, we emphasize the importance of distinguishing between the total
      formation free energy of a cluster, and the nucleation free energy, which
      involves only those steps contributing to the free energy barrier. We have
      separately considered how the ion-water potential energy, the water-water
      potential energy, and the entropy contribute to both the cluster formation free
      energy, and the nucleation free energy. These simulations have shown that while
      the ion-water potential energies make the largest contribution to the formation
      free energy difference between positive and negative ions, the entropy is the
      contribution leading to lower nucleation free energy barriers for negative ions.
      The primary reason for this is the larger stable (but precritical) clusters
      formed around negative ions. We have further shown that the distinction between
      formation and nucleation free energies is of particular importance when comparing
      small cations with larger anions where the formation free energies can be much
      lower for the cationic clusters, even though the nucleation barriers are lower
      for the anionic clusters.

PMID- 23145733
TI  - Pairing of 1-hexyl-3-methylimidazolium and tetrafluoroborate ions in n-pentanol.
AB  - Molecular dynamics simulations are obtained and analyzed to study pairing of 1
      hexyl-3-methylimidazolium and tetrafluoroborate ions in n-pentanol, in particular
      by evaluating the potential-of-mean-force between counter ions. The present
      molecular model and simulation accurately predicts the dissociation constant K(d)
      in comparison to experiment, and thus the behavior and magnitudes for the ion
      pair potential-of-mean-force at molecular distances, even though the dielectric
      constant of the simulated solvent differs from the experimental value by about
      30%. A naive dielectric model does not capture molecule structural effects such
      as multiple conformations and binding geometries of the Hmim(+) and BF(4)(-) ion
      pairs. Mobilities identify multiple time-scale effects in the autocorrelation of
      the random forces on the ions, and specifically a slow, exponential time-decay of
      those long-ranged forces associated here with dielectric friction effects.

PMID- 23145734
TI  - Phase diagram of the modified Lennard-Jones system.
AB  - An investigation of the precise determination of melting temperature in the
      modified Lennard-Jones system under pressure-free conditions [Y. Asano and K.
      Fuchizaki, J. Phys. Soc. Jpn. 78, 055002 (2009)] was extended under finite
      pressure conditions to obtain the phase diagram. The temperature and pressure of
      the triple point were estimated to be 0.61 epsilon/k(B) and 0.0018(5)
      epsilon/sigma(3), and those of the critical point were 1.0709(19) epsilon/k(B)
      and 0.1228(20) epsilon/sigma(3), where epsilon and sigma are the Lennard-Jones
      parameters for energy and length scales, respectively, and k(B) is the Boltzmann
      constant. The potential used here has a finite attractive tail and does not
      suffer from cutoff problems. The potential can thus be a useful standard in
      examining statistical-mechanical problems in which different treatments for the
      tail would lead to different conclusions. The present phase diagram will then be
      a useful guide not only for equilibrium calculations but also for nonequilibrium
      problems such as discussions of the limits of phase (in)stability.

PMID- 23145735
TI  - Semiquantal molecular dynamics simulations of hydrogen-bond dynamics in liquid
      water using multi-dimensional Gaussian wave packets.
AB  - A semiquantal (SQ) molecular dynamics (MD) simulation method based on an extended
      Hamiltonian formulation has been developed using multi-dimensional thawed
      gaussian wave packets (WPs), and applied to an analysis of hydrogen-bond (H-bond)
      dynamics in liquid water. A set of Hamilton's equations of motion in an extended
      phase space, which includes variance-covariance matrix elements as auxiliary
      coordinates representing anisotropic delocalization of the WPs, is derived from
      the time-dependent variational principle. The present theory allows us to perform
      real-time and real-space SQMD simulations and analyze nuclear quantum effects on
      dynamics in large molecular systems in terms of anisotropic fluctuations of the
      WPs. Introducing the Liouville operator formalism in the extended phase space, we
      have also developed an explicit symplectic algorithm for the numerical
      integration, which can provide greater stability in the long-time SQMD
      simulations. The application of the present theory to H-bond dynamics in liquid
      water is carried out under a single-particle approximation in which the variance
      covariance matrix and the corresponding canonically conjugate matrix are reduced
      to block-diagonal structures by neglecting the interparticle correlations. As a
      result, it is found that the anisotropy of the WPs is indispensable for
      reproducing the disordered H-bond network compared to the classical counterpart
      with the use of the potential model providing competing quantum effects between
      intra- and intermolecular zero-point fluctuations. In addition, the significant
      WP delocalization along the out-of-plane direction of the jumping hydrogen atom
      associated with the concerted breaking and forming of H-bonds has been detected
      in the H-bond exchange mechanism. The relevance of the dynamical WP broadening to
      the relaxation of H-bond number fluctuations has also been discussed. The present
      SQ method provides the novel framework for investigating nuclear quantum dynamics
      in the many-body molecular systems in which the local anisotropic fluctuations of
      nuclear WPs play an essential role.

PMID- 23145736
TI  - Molecular dynamics simulation of the spherical electrical double layer of a soft
      nanoparticle: effect of the surface charge and counterion valence.
AB  - Molecular dynamics simulations were performed to study the ion and water
      distribution around a spherical charged nanoparticle. A soft nanoparticle model
      was designed using a set of hydrophobic interaction sites distributed in six
      concentric spherical layers. In order to simulate the effect of charged
      functionalyzed groups on the nanoparticle surface, a set of charged sites were
      distributed in the outer layer. Four charged nanoparticle models, from a surface
      charge value of -0.035 C m(-2) to -0.28 C m(-2), were studied in NaCl and CaCl(2)
      salt solutions at 1 M and 0.1 M concentrations to evaluate the effect of the
      surface charge, counterion valence, and concentration of added salt. We obtain
      that Na(+) and Ca(2+) ions enter inside the soft nanoparticle. Monovalent ions
      are more accumulated inside the nanoparticle surface, whereas divalent ions are
      more accumulated just in the plane of the nanoparticle surface sites. The
      increasing of the the salt concentration has little effect on the internalization
      of counterions, but significantly reduces the number of water molecules that
      enter inside the nanoparticle. The manner of distributing the surface charge in
      the nanoparticle (uniformly over all surface sites or discretely over a limited
      set of randomly selected sites) considerably affects the distribution of
      counterions in the proximities of the nanoparticle surface.

PMID- 23145737
TI  - A van der Waals density functional study of chloroform and other trihalomethanes
      on graphene.
AB  - A computational study of chloroform (CHCl(3)) and other trihalomethanes (THMs)
      adsorbed on graphene is presented. The study uses the van der Waals density
      functional method to obtain adsorption energies and adsorption structures for
      these molecules of environmental concern. In this study, chloroform is found to
      adsorb with the H atom pointing away from graphene, with adsorption energy 357
      meV (34.4 kJ/mol). For the other THMs studied the calculated adsorption energy
      values vary from 206 meV (19.9 kJ/mol) for fluoroform (CHF(3)) to 404 meV (39.0
      kJ/mol) for bromoform (CHBr(3)). The corrugation of graphene as seen by the THMs
      is small, the difference in adsorption energy along the graphene plane is less
      than 6 meV for chloroform.

PMID- 23145738
TI  - Potassium spin polarization lifetime for a 30-carbon chain siloxane film.
AB  - The siloxane film derived from the 30-carbon chain triacontyltrichlorosilane
      (TCTS) is studied as an anti-relaxation coating for atomic vapor cells. The
      longitudinal spin relaxation lifetime of optically pumped potassium atoms in the
      presence of TCTS is measured and the average number of non-relaxing atom-wall
      collisions, or bounces, enabled by the coated surface is determined. X-ray
      photoelectron spectroscopy (XPS) and atomic force microscopy (AFM) of TCTS were
      performed to investigate changes in chemical states and surface morphology of
      TCTS arising from K atom deposition on the film surface. TCTS was found to give
      approximately 530 bounces. Following lifetime measurements, K2p signals were
      clearly observed in XPS spectra. AFM images display non-preferential K deposition
      on the TCTS surface, however additional AFM studies with a TCTS surface exposed
      to Rb atoms show deposition occurs along surface defects. In agreement, Rb is
      found to preferentially deposit along the step edges of an 18-carbon chain
      monolayer film derived from 1-Octadecene. Finally, AFM indicates a much smoother
      surface for a tetracontane coating relative to TCTS. The importance of siloxane
      surface morphology versus film thickness with respect to coating performance is
      discussed.

PMID- 23145739
TI  - Attraction between neutral dielectrics mediated by multivalent ions in an
      asymmetric ionic fluid.
AB  - We study the interaction between two neutral plane-parallel dielectric bodies in
      the presence of a highly asymmetric ionic fluid, containing multivalent as well
      as monovalent (salt) ions. Image charge interactions, due to dielectric
      discontinuities at the boundaries, as well as effects from ion confinement in the
      slit region between the surfaces are taken fully into account, leading to image
      generated depletion attraction, ion correlation attraction, and steric-like
      repulsive interactions. We investigate these effects by employing a combination
      of Monte Carlo simulation methods, including explicit-ion simulations (where all
      electrostatic interactions are simulated explicitly) and implicit-ion simulations
      (where monovalent ions are replaced by an effective screened electrostatic
      potential between multivalent ions), as well as an approximate analytical theory.
      The latter incorporates strong ion-image charge correlations, which develop in
      the presence of high valency ions in the mixture. We show that the implicit-ion
      simulations and the proposed analytical theory can describe the explicit
      simulation results on a qualitative level, while excellent quantitative agreement
      can be obtained for sufficiently large monovalent salt concentrations. The
      resultant attractive interaction between the neutral surfaces is shown to be
      significant, as compared with the usual van der Waals interactions between semi
      infinite dielectrics, and can thus play an important role at the nano scale.

PMID- 23145740
TI  - The structure of N2 adsorbed on the rumpled NaCl(100) surface--a combined LEED
      and DFT-D study.
AB  - The structure of N(2) physisorbed on the NaCl(100) single crystal surface is
      investigated by means of quantitative low-energy electron diffraction (LEED) in
      combination with dispersion corrected density functional theory (DFT-D). In the
      temperature range between 20 K and 45 K, a p(1 * 1) structure is observed in the
      LEED experiment. According to the structure analysis based on the measured
      diffraction spot intensity profiles, the N(2) molecules are adsorbed over the
      topmost Na(+) ions. The experimental distance of the lower nitrogen to the Na(+)
      ion underneath is (2.55 +/- 0.07) A; the corresponding DFT-D value is 2.65 A. The
      axes of the molecules are tilted (26 +/- 3) degrees  with respect to the surface
      normal, while in the zero Kelvin optimum structure from DFT-D, the molecules have
      a perpendicular orientation. The experimental monolayer heat of adsorption,
      deduced from a Fowler-Guggenheim kinetic model of adsorption is -(13.6 +/- 1.6)
      kJ mol(-1), including a lateral molecule-molecule interaction energy of -(2.0 +/-
      0.4) kJ mol(-1). The zero Kelvin adsorption energy from DFT-D, including zero
      point energy correction, is -15.6 kJ mol(-1); the molecule-molecule interaction
      is -2.4 kJ mol(-1). While the rumpling of the NaCl(100) surface is unchanged upon
      adsorption of nitrogen, the best-fit root mean square thermal displacements of
      the ions in the topmost substrate layer are significantly reduced.

PMID- 23145741
TI  - Frictional properties of two alkanethiol self assembled monolayers in sliding
      contact: odd-even effects.
AB  - Using molecular dynamics simulation, we have investigated the structural effects
      on the frictional properties of self assembled monolayers (SAM) of n-alkanethiols
      [CH(3)(CH(2))(n-1)SH, n = 12-15] in SAM-SAM contacts attached on Au (111)
      substrates. We have observed an odd-even effect where friction coefficient for
      SAM-SAM contacts with n = odd showed consistently higher values than those with n
      = even. This odd-even effect is independent of the sliding velocity and the
      relative tilt directions of the SAMs, and persists over a much higher pressure
      range than that reported before for SAM-Au contacts [L. Ramin and A. Jabbarzadeh,
      Langmuir 28, 4102-4112 (2012)]. For odd systems higher gauche defects were shown
      to be the possible source of high friction coefficient. Under the same load and
      shear rates (comparable sliding velocities), SAM-SAM contacts show mostly higher
      friction compared to SAM-Au contacts. For SAM-SAM contacts, a more significant
      increase of friction occurs at higher shear rates due to a shift in the tilt
      orientation angle. We show SAM-SAM contacts with misaligned relative tilt
      orientation angle (~45 degrees -90 degrees ) have considerably lower friction
      compared with those whose tilt orientation angles are almost aligned in the
      opposite directions and parallel to the shear.

PMID- 23145742
TI  - Looking deeper into the structure of mixed electric double layers near the point
      of zero charge.
AB  - Molecular simulations have been carried out using the Metropolis Monte Carlo
      approach to investigate the structure of planar electric double layers containing
      counterion mixture within the framework of the unrestricted primitive model. The
      results reveal that near the point of zero charge, the rise of monovalent salt
      drastically elevates the collapse of ions regardless of their polarity. In
      particular, we fail to observe the formation of a strongly correlated liquid in
      the first counterion layer due to favorable entropic effects, in contrast to the
      early data from molecular dynamics simulations [corrected] for a spherical
      electric double layer [R. Messina, E. Gonzalez-Tovar, M. Lozada-Cassou, and C.
      Holm, Europhys. Lett. 60, 383 (2002)]. Moreover, the large size of coions is
      found to be a pivotal factor in determining the reversal of electrophoretic
      mobility. On the other hand, the repulsive image charge forces thoroughly
      annihilate this peculiar reversal of mobility within the investigated scope of
      concentrations, but exert no effect on the emergence of charge reversal. These
      findings highlight potential applications of coion's characteristics to control
      gene delivery and colloidal stability as well as to design viral packing and
      polyelectrolyte self-assembly.

PMID- 23145743
TI  - Methodological aspects of the quantum-chemical description of interface dipoles
      at tetrathiafulvalene/tetracyanoquinodimethane interfaces.
AB  - The formation of dipoles at interfaces between organic semiconductors is expected
      to play a significant role in the operation of organic-based devices, though the
      electronic processes at their origin have still to be clearly elucidated. Quantum
      chemical calculations can prove very useful to shed light on such electronic
      interfacial phenomena provided that a suitable theoretical approach is used. In
      this context, we have performed calculations on small vertical stacks of TTF-TCNQ
      molecules, first at the CAS-MRCI level to validate the use of single
      determinantal approaches, then at the MP2 level set as a benchmark. Various
      density functional theory (DFT) functionals have then been applied to larger
      stacks, showing that long-range corrected functionals are required to reproduce
      MP2 results taken as benchmark. Finally, the use of periodic boundary conditions
      at the DFT level points to the huge impact of depolarization effects between
      adjacent stacks.

PMID- 23145744
TI  - Surface roughening in polymer blend thin films by lateral phase separation: a
      thermodynamic mechanism.
AB  - We use a phase portrait approach to study the phase equilibria of a symmetric
      binary polymer blend confined between an attracting wall and a neutral wall. We
      find multiple solutions for this wall regime where only one solution exists for
      antisymmetric walls. We also argue that, when one wall is a free surface,
      roughening of the free surface upon lateral phase separation is expected, since
      thermodynamics alone implies that the coexisting phases should exist at different
      heights to minimise energy. We focus on the graphical insight provided by this
      phase portrait approach.

PMID- 23145745
TI  - Scattering function of semiflexible polymer chains under good solvent conditions.
AB  - Using the pruned-enriched Rosenbluth Monte Carlo algorithm, the scattering
      functions of semiflexible macromolecules in dilute solution under good solvent
      conditions are estimated both in d = 2 and d = 3 dimensions, considering also the
      effect of stretching forces. Using self-avoiding walks of up to N = 25,600 steps
      on the square and simple cubic lattices, variable chain stiffness is modeled by
      introducing an energy penalty epsilon(b) for chain bending; varying q(b) = exp (
      epsilon(b)/k(B)T) from q(b) = 1 (completely flexible chains) to q(b) = 0.005, the
      persistence length can be varied over two orders of magnitude. For unstretched
      semiflexible chains, we test the applicability of the Kratky-Porod worm-like
      chain model to describe the scattering function and discuss methods for
      extracting persistence length estimates from scattering. While in d = 2 the
      direct crossover from rod-like chains to self-avoiding walks invalidates the
      Kratky-Porod description, it holds in d = 3 for stiff chains if the number of
      Kuhn segments n(K) does not exceed a limiting value n(K)(*) (which depends on the
      persistence length). For stretched chains, the Pincus blob size enters as a
      further characteristic length scale. The anisotropy of the scattering is well
      described by the modified Debye function, if the actual observed chain extension
      <X> (end-to-end distance in the direction of the force) as well as the
      corresponding longitudinal and transverse linear dimensions <X(2)> - <X>(2),
      <R(g,?)(2)> are used.

PMID- 23145746
TI  - Electrostatic interactions mediated by polarizable counterions: weak and strong
      coupling limits.
AB  - We investigate the statistical mechanics of an inhomogeneous Coulomb fluid
      composed of charged particles with static polarizability. We derive the weak- and
      the strong-coupling approximations and evaluate the partition function in a
      planar dielectric slab geometry with charged boundaries. We investigate the
      density profiles and the disjoining pressure for both approximations. Comparison
      to the case of non-polarizable counterions shows that polarizability brings
      important differences in the counterion density distribution as well as the
      counterion mediated electrostatic interactions between charged dielectric
      interfaces.

PMID- 23145747
TI  - Dielectric relaxation change of water upon phase transition of a lipid bilayer
      probed by terahertz time domain spectroscopy.
AB  - We investigate the influence of the 1, 2-ditetradecanoyl-sn-glycero-3
      phosphocholine lipid bilayer phases on the water reorientation dynamics with
      terahertz time domain spectroscopy. The phase of the lipids was controlled by the
      temperature in the range of 14-35  degrees C. During the gel-to-fluid phase
      transition, the hydration water ratio drastically changed from 0.3 to 0.6. The
      absorption coefficient of the hydration water increased with the temperature in
      the gel phase and then decreased in the fluid phase. The dielectric relaxation
      time of the lipid solution decreased initially but then increased after the phase
      transition. This indicates that the hydration water reorientation dynamics are
      restricted by lipids and that this phenomenon is pronounced in a biologically
      relevant fluid phase.

PMID- 23145748
TI  - Subdiffusion of proteins and oligomers on membranes.
AB  - Diffusion of proteins on lipid membranes plays a central role in cell signaling
      processes. From a mathematical perspective, most membrane diffusion processes are
      explained by the Saffman-Delbruck theory. However, recent studies have suggested
      a major limitation in the theoretical framework, the lack of complexity in the
      modeled lipid membrane. Lipid domains (sometimes termed membrane rafts) are known
      to slow protein diffusion, but there have been no quantitative theoretical
      examinations of how much diffusion is slowed in a general case. We provide an
      overall theoretical framework for confined-domain ("corralled") diffusion.
      Further, there have been multiple apparent contradictions of the basic
      conclusions of Saffman and Delbruck, each involving cases in which a single
      protein or an oligomer has multiple transmembrane regions passing through a lipid
      phase barrier. We present a set of corrections to the Saffman-Delbruck theory to
      account for these experimental observations. Our corrections are able to provide
      a quantitative explanation of numerous cellular signaling processes that have
      been considered beyond the scope of the Saffman-Delbruck theory, and may be
      extendable to other forms of subdiffusion.

PMID- 23145751
TI  - Photoinduced monolayer patterning for the creation of complex protein patterns.
AB  - This work investigates self-assembled monolayers that were formed from a glycol
      terminated thiol monomer and were patterned using photoinduced monolayer
      desorption. Utilizing direct-write photolithography provided a facile means to
      generate complex protein patterns containing gradients and punctate regions. The
      ablated glycol monolayers were characterized using scanning probe microscopy,
      which allowed us to observe differences in the nanomechanical properties between
      the patterned and nonpatterned regions of the substrate. The patterned regions on
      the surface adsorbed proteins, and this process was monitored quantitatively
      using surface plasmon resonance imaging (SPRi). Moreover, the concentration of
      the protein could be controlled accurately by simply setting the gray level in
      the 8-bit image. Adsorbed protein was probed using a commercially available
      antibody binding assay, which showed significant enhancement over the background.
      The ability to produce complex protein patterns will contribute greatly to
      creating in vitro models that more accurately mimic an in vivo environment.

PMID- 23145752
TI  - What is the best choice for displaced femoral neck fractures in the elderly?
      Internal fixation or total/hemiarthroplasty.

PMID- 23145753
TI  - [Functional outcomes and quality of life in patients with proximal row
      carpectomy].
AB  - OBJECTIVES: This study aims to assess pain, functional status, patient
      satisfaction, and quality of life in patients with proximal row carpectomy.
      PATIENTS AND METHODS: Between December 2007 and November 2011, demographic,
      clinical, and operational data, and physical therapy program of 16 patients (11
      males, 5 females; mean age 41.4+/-16.6 years; range 19 to 77 years) with proximal
      row carpectomy were recorded. Pain (0-no pain, 10-severe pain), and patient
      satisfaction (0-not satisfied, 10-very satisfied) were assessed with visual
      analog scale (VAS). Wrist range of motion, and hand grip strength were evaluated.
      The quick-disabilities of the arm, shoulder and hand (Q-DASH), and Mayo wrist
      score were used for functional evaluation of the upper limb. Short form-36 (SF
      36) was used for the evaluation of quality of life. RESULTS: Postsurgical
      duration was 20.6+/-16.4 (range; 6-56) months. Complex regional pain syndrome
      (CRPS) was detected in two patients (%12.5). The mean session numbers of physical
      therapy were 16.7+/-9.4 (range; 0-30), satisfaction VAS was 8.4+/-2.1, rest VAS
      0.8+/-0.9, activity VAS was 2.3+/-2.2, grip strength of operated side 82% of
      nonoperated side, Q-DASH score was 13.4+/-16.5 (substantially good), and Mayo
      wrist score was 80.0+/-19.4 (good). Significant improvement was detected in
      postoperative flexion-extension arc compared to preoperative status (p=0.001). A
      correlation was detected between hand grip strength percentage and session
      numbers of physical therapy (p=0.025, r=0.558). Relationships between quality of
      life-pain subscore and activity pain (p=0.001, r= -0.819), Q-DASH (p=0.003, r= 
      0.698), and Mayo wrist score (p=0.037, r=0.525) were detected. The presence of
      complication was the only independent variable for prediction of functional
      status in multivariate linear regression analysis. CONCLUSION: Increased number
      of physical therapy session results in improved hand grip strength following the
      proximal row carpectomy, while CRPS complication which can be seen after surgery
      affects the functional status adversely.

PMID- 23145754
TI  - Is proximal tibia the major problem in varus gonarthrosis? Evaluation of femur
      and ankle.
AB  - OBJECTIVES: In this study, we aimed to evaluate the components of knee varus in
      the adjacent joints and to investigate the possible correlations between them.
      PATIENTS AND METHODS: Between January 2005 and December 2010, 315 lower limbs of
      164 patients who underwent high tibial osteotomy (HTO) due to varus gonarthrosis
      were analyzed. Alignment and orientation angles of these limbs using preoperative
      orthoroentgenography were measured. The results were compared with normal values
      and evaluated statistically for possible correlations. RESULTS: Statistical
      analysis of the data showed that the mean value of mechanical lateral distal
      femoral angle (mLDFA) increases in varus knees and thus distal femoral joint
      orientation showed less valgus. The effect of mLDFA on mechanical tibiofemoral
      angle (mTFA) was almost the same as medial proximal tibial angle (MPTA). Both
      together; they explain 52.2% of variance in mTFA. mLDFA has a negative and MPTA
      has a positive and significant influence on mTFA (b= -0.765, p<0.001) and (b=
      0.798, p<0.001) respectively. A moderate correlation was found between the mTFA
      and lateral distal tibial angle (LDTA) in the lower limbs grounding at the same
      angle (r=0.634, R=0.40, p<0.001). A slight, but significant correlation between
      mTFA and medial neck shaft angle (MNSA) was found (r=0.15, R=0.02, p<0.01).
      CONCLUSION: Distal femoral joint showing less valgus significantly contributes to
      the deformity in varus gonarthrosis, also a very important contributor to the
      deformity. Abnormal forces applied to ankle may cause collapse in distal lateral
      tibial metaphysis and decrease LDTA in varus knees. Medial neck shaft angle may
      decrease due to possible abnormal loading angles to the femoral neck in some
      individuals with varus gonarthrosis.

PMID- 23145755
TI  - [A comparison of the efficacy of bupivacaine and levobupivacaine in patient
      controlled epidural analgesia for postoperative pain in patients undergoing knee
      arthroplasty].
AB  - OBJECTIVES: In this study, we aimed to compare the efficacy of bupivacaine and
      levobupivacaine in the patient-controlled epidural analgesia (PCEA) in patients
      who underwent total knee arthroplasty (TKA), particularly with cardiac diseases.
      PATIENTS AND METHODS: Forty-four patients (16 males, 28 females; mean age 70.2+/
      6.3 years; range 18 to 80 years) who were scheduled for TKA surgery under
      combined spinal and epidural anesthesia were included. Patients were randomly
      divided into two groups. Bupivacaine 15 mg 0.5% for group 1 (n=23) and
      levobupivacaine 15 mg 0.5% for group (n=23) were administered via spinal route.
      The amount of local anesthetics, PCEA starting times and bolus/demand ratio of
      local anesthetics were recorded. The level of pain, need for additional
      analgesic, total amount of analgesic, degree of motor block, complications were
      asked for patient satisfaction at postoperative 6, 12, 24 and 48 hours. RESULTS:
      No statistical differences were determined between group 1 and group 2 in terms
      of the operation times, PCEA starting times, bolus number/demand ratios, visual
      analog scale (VAS) scores and numerical rating scores (NRS) at the postoperative
      6, 12, 24 and 48 hours, need for additional analgesic, total amount of analgesic,
      degree of motor block and patient satisfaction. Although the incidence of side
      effects was lower in the group 1 compared to group 2, it was not statistically
      significant. CONCLUSION: We concluded that it would be proper using
      levobupivacaine rather than bupivakaine for patients with cardiac diseases, as
      the cardiotoxic and neurotoxic effects of levobupivacaine is lower then
      bupivacaine with a similar analgesic efficacy.

PMID- 23145756
TI  - A comparison of clinical outcome of augmentation and standard reconstruction
      techniques for partial anterior cruciate ligament tears.
AB  - OBJECTIVES: This study aims to compare the clinical outcome and possible
      complications of augmentation technique and standard reconstruction for the
      treatment of partial anterior cruciate ligament (ACL) tears. PATIENTS AND
      METHODS: Forty patients (36 males, 4 females; mean age 30 years; range 19 to 40
      years) who underwent surgery due to ACL tear were included in this prospective
      randomized study. The patients were randomly divided into two groups, including
      20 patients in each group. The patients in the group 1 underwent standard single
      bundle ACL reconstruction with hamstring tendon autografts, while those in the
      group 2 underwent augmentation where the remaining remnant ACL was not
      sacrificed, but instead augmented with hamstring tendon autograft as in the
      standard reconstruction technique. The mean follow-up was 24.3 months (range; 21
      28 months). Clinical outcomes were evaluated using International Knee
      Documentation Committee (IKDC), Lysholm scores, physical instability tests and
      patient satisfaction questionnaires. The complication rates of both groups were
      compared. Tibial and femoral tunnel widening were assessed using lateral and
      anteroposterior radiographs. RESULTS: No significant differences were found
      between the groups in terms of IKDC, Lysholm scores, physical instability tests,
      patient satisfaction questionnaires and incidences of Cyclops lesions and
      arthrofibrosis. Tibial and femoral tunnel widening was less in the augmentation
      group. This difference was more significant on the tibial side. CONCLUSION: In
      the repair of partial ACL tears, augmentation technique is as effective as the
      standard technique, leading to, less tunnel widening evidently in the tibial
      tunnel, particularly.

PMID- 23145757
TI  - [The effectivity of magnetic resonance imaging findings in the diagnosis of
      bucket handle meniscal tears].
AB  - OBJECTIVES: This study aims to test the efficacy of magnetic resonance imaging
      (MRI) evaluation by a group who were blinded to the arthroscopic diagnosis in
      patients with known bucket handle meniscal tears. PATIENTS AND METHODS: In this
      study, MRI scans of 28 patients who were operated due to bucket handle meniscal
      tear with sufficient documentation were evaluated. Radiographic evaluation was
      performed by two different groups, including an orthopedist and radiologist. In
      the first group, evaluation of MRI scans was performed by the specialists who
      were aware of the arthroscopic diagnosis and marked the defined MRI signs of
      bucket handle meniscal tear. In the second group, evaluation was done, remaining
      blinded to the diagnosis, with only initial complaints at admission. The second
      group also evaluated the MRI scans and marked the pathologic signs. The
      sensitivity of radiological signs marked by both groups was compared. Invariables
      were found using blinded evaluation. RESULTS: Double posterior cruciate ligament
      and free fragment in the intercondylar notch were invariable sensitivities found
      in the MRI scans by blinded evaluation. The sensitivity of coronal truncation,
      anterior flip and any free fragment signs were significantly decreased in the
      setting of blinded evaluation. CONCLUSION: Preoperative differentiation of
      reparable bucket-handle tears from irreparable is of utmost importance. As
      meniscal repair improves knee stability and functional results, surgical repair
      of meniscal injuries particularly in younger individuals who are scheduled for
      anterior cruciate ligament reconstruction have a positive effect on clinical
      outcomes.

PMID- 23145758
TI  - [Humeral shaft nonunions: plates and nails].
AB  - OBJECTIVES: This study aims to compare the functional results of dynamic
      compression plates (DCP) and interlocked retrograde intramedullary nails (IRIN)
      used for the treatment of humeral shaft nonunions. PATIENTS AND METHODS: Twenty
      six patients (12 males, 14 females; mean age, 42.8 years; range 21 to 61 years)
      who underwent surgical treatment of humeral shaft nonunion either with DCP (n=13)
      or IRIN (n=13) between October 1999 and January 2008, were retrospectively
      analyzed. Treatment consisted of removing previous implants and DCP or IRIN
      fixation with additional autogenous bone grafts for atrophic nonunions. Union
      time, range of motion, radiographic length difference, Constant-Murley Scale
      (CMS), Disabilities of the Arm, Shoulder and Hand (DASH-T) and Mayo Elbow
      Performance Score (MEPS) were evaluated at a mean follow-up time of 59.5 months
      (range; 17 to 125 months). RESULTS: There was a statistically significant
      correlation among the functional scores of DASH-T, MEPS and CMS. No statistically
      significant difference was observed in the functional outcome between the groups
      (DCP and IRIN). Range of motion of the elbow joint was significantly impaired in
      three patients who were plated for distal shaft nonunions. CONCLUSION: Both DCP
      and IRIN provide satisfactory functional outcomes in the treatment of humeral
      shaft nonunions. Distal shaft nonunions may demonstrate a decrement in elbow
      motion associated with distal placement of plates.

PMID- 23145759
TI  - [A clinical analysis of patients undergoing fasciotomy who experienced the 2011
      Van earthquake].
AB  - OBJECTIVES: This study aims to investigate the clinical profile and prognosis of
      the patients with fasciotomy who were admitted to Van Training and Research
      Hospital following the 2011 Van earthquake. PATIENTS AND METHODS: Twenty-one
      patients (11 males, 10 females; mean age 38.3 years; range 18 to 60 years) who
      had urgent fasciotomy in our clinic following the earthquake were included.
      Medical records including demographic data, clinical characteristics and
      prognostic data of the patients were retrospectively analyzed. RESULTS: Seven of
      21 patients with fasciotomies underwent amputation. Fasciotomy incisions were
      closed with skingrafting in nine patients and with primary closure in three
      patients. Eight patients had full range of motion of the joint, while four
      patients had restricted range of motion of the joint and needed rehabilitation.
      Two patients had sensory loss. CONCLUSION: Compartment syndrome is one of the
      serious problems after the Van earthquake. The infection ratio was low, while the
      amputation ratio was high. The use of anticoagulants following compartment
      syndrome worsens the clinical presentation, increasing the intracompartmental
      pressure.

PMID- 23145760
TI  - Dorsal cutaneous innervation of the hand with respect to anatomical landmarks: is
      there a safe zone?
AB  - OBJECTIVES: In this study, we aimed to define the borders of the triangular area
      between the radial and dorsal nerves on the dorsum of the hand and to determine
      its dimensions using measurements between anatomic landmarks. MATERIALS AND
      METHODS: We statistically analyzed the relation between the distance from
      Lister's tubercle to the blending point of the central branches of radial and
      ulnar nerves and the distance between styloids on 14 hands of seven adult human
      cadavers (5 males, 2 females). The distances of nerve branches to vertical lines
      drown distally from both styloid processes were also compared with interstyloid
      distances to help in presuming the course of these nerves. RESULTS: No
      statistical constant correlation was determined between the measurements. Neither
      the height of the triangular area nor the courses of both nerves seemed to be
      quantitatively related to any measurements between the anatomical landmarks.
      CONCLUSION: Variability in these measurements in our study indicates that there
      is no surgical safe zone on the dorsum of the hand.

PMID- 23145761
TI  - Does tranexamic acid reduce blood loss and blood transfusion requirement in knee
      arthroplasty?
AB  - Strong evidences which indicate that tranexamic acid reduces blood loss and blood
      transfusion requirement in patients who are scheduled for total knee arthroplasty
      are available. However, dose and method of administration, safety and side
      effects are still controversial issues. The effect of tranexamic acid on
      thromboembolic events and mortality is still unknown.

PMID- 23145762
TI  - [Long-term use of fondaparinux in major orthopedic surgery].
AB  - OBJECTIVES: This study aims to investigate whether the usage of fondaparinux
      sodium may result in major hemorrhages following major orthopedic surgery.
      PATIENTS AND METHODS: Forty-three patients (30 females and 13 males; mean age 66
      years; range 34 to 94 years) at the age of >18 years who were scheduled for major
      orthopedic surgery were included. Total hip arthroplasty, total knee arthroplasty
      and proximal femur fracture surgeries were defined as the major orthopedic
      surgeries. Prophylaxis was administered with 2.5 mg fondaparinux sodium once
      daily subcutaneously. Prophylaxis was initiated at 6-8 hours after the closure of
      incision. During the prophylaxis period (31+/-3 days), the patients were
      monitored for symptomatic deep venous thrombosis. Serum creatinine, platelet and
      hemoglobin levels were measured at the baseline and in the first week and at one
      month postoperatively. Wound healing time, healing complications, and major/minor
      hemorrhages seen during the prophylaxis period were recorded. RESULTS: During the
      follow-up, none of the patients had symptomatic deep vein thrombosis or
      symptomatic pulmonary embolism. Two patients (4.6%) had delayed wound healing,
      while four (9.3%) had minor ecchymosis. No major hemorrhages were observed in any
      patients. CONCLUSION: With the long-term use of fondaparinux, we did not observe
      any major hemorrhagic complications. However, further large-scale studies
      including control groups are required to establish the effects of long-term use
      of fondaparinux.

PMID- 23145763
TI  - [Hydatid cyst involvement of shoulder and deltoid muscle: a case report].
AB  - Hydatid cyst is seen an endemic disease in many countries in the world. Cysts
      arising from Echinococcus granulosis occur most commonly in the liver and
      secondly in the lungs. Primary cystic involvement in the musculoskeletal system
      without lung or liver involvement is very rare. Treatment consists of surgical
      resection. Anthelmintic medication before and after surgery can be used. In this
      article, we present a very rare case of 29-year-old female with hydatid cyst
      involving shoulder, starting from subcutaneous tissue and extending up to the
      deltoid muscle. The patient was managed with surgical resection and anthelmintic
      drugs.

PMID- 23145764
TI  - Multiple osteochondromatosis complicated with a popliteal artery pseudoaneurysm.
AB  - In this article, we present a 21-year-old male patient who presented with
      swelling and pain located to right lower thigh and knee. Physical examination and
      subsequent diagnostic work-up revealed a pseudoaneurysm associated with an
      osteochondroma at lower thigh. This complication should be considered in young
      patients with a mass at knee and lower thigh region.

PMID- 23145765
TI  - The effect of acupuncture on stroke recovery: study protocol for a randomized
      controlled trial.
AB  - BACKGROUND: Stroke is one of the leading causes of death and disability in China.
      Current treatments for stroke are limited and achieve no optimal effect.
      Acupuncture is widely used in the treatment of stroke and in improving the
      quality of life for patients in China. In most previous clinical studies, the
      effects of acupuncture have been diverse, and few well-designed randomized
      controlled trials have been conducted to investigate the long-term effect of
      acupuncture on acute stroke recovery. METHOD: Three hundred and twenty eight
      subjects with acute cerebral apoplexy will be recruited. The patients will be
      randomized into two different groups: the intervention group will receive
      acupuncture treatment together with Western standard treatment for 2 weeks plus
      the secondary prevention treatment for 22 weeks; the control group will receive
      only the Western standard treatment for 2 weeks and the secondary prevention
      treatment for 22 weeks. The primary outcome measures are Barthel Index and the
      Stroke-Specific Quality Of Life. The secondary outcome measures are the National
      Institutes of Health Stroke Scale and Modified Rankin Scale. All assessments will
      be conducted at the baseline and at weeks 4, 12 and 24 of follow-up. DISCUSSION:
      This study will evaluate the effects of acupuncture on the long-term recovery of
      acute stroke and on improving the quality of life of the patients. The results of
      this study will help establish optimal integrated therapeutic strategies for
      patients with stroke. TRIAL REGISTRATION: Current Controlled Trials
      ISRCTN29932220.

PMID- 23145766
TI  - Photodynamic tumor eradication with a novel targetable photosensitizer: strong
      vascular effects and dependence on treatment repetition versus potentiation.
AB  - A novel pyropheophorbide-a (PPa) derivative, Ac-sPPp, was developed in our lab
      for targeted photodynamic therapy (PDT) and combination therapies. Its versatile
      peptide moiety, high water-solubility, amphiphilicity, and micellar aggregation
      allow efficient coupling to targeting moieties and convenient mixing with other
      therapeutics. Photosensitizer immunoconjugate (PIC) targeted PDT, using Ac-sPPp
      conjugated to therapeutic anti-epidermal growth factor receptor (EGFR) antibody
      cetuximab, and PDT + chemotherapy combination treatment, using Ac-sPPp mixed with
      stealth liposomal doxorubicin (Doxil), were investigated as promising strategies
      for potentiating PDT and improving target specificity. Passively targeted PDT
      with Ac-sPPp only or surfactant-solubilized PPa was also investigated for
      comparison. The A-431 human vulvar squamous cell carcinoma, xenografted in nude
      mice, was chosen as a tumor model because of its high EGFR expression and
      sensitivity to liposomal doxorubicin in vitro. Fluorescence imaging and PDT
      experiments showed that Ac-sPPp formulations circulated far longer and provided
      superior tumor contrast and superior tumor control compared to PPa. Strong PDT
      vascular effects were observed by laser Doppler imaging regardless of whether Ac
      sPPp was passively or actively targeted. Passively targeted Ac-sPPp PDT gave
      equivalent or better tumor control than PIC-targeted PDT or PDT + Doxil
      combination therapy, and when treatments were repeated, it also yielded the
      highest cure rate.

PMID- 23145767
TI  - Comparative genomics of bacteria in the genus Providencia isolated from wild
      Drosophila melanogaster.
AB  - BACKGROUND: Comparative genomics can be an initial step in finding the genetic
      basis for phenotypic differences among bacterial strains and species. Bacteria
      belonging to the genus Providencia have been isolated from numerous and varied
      environments. We sequenced, annotated and compared draft genomes of P. rettgeri,
      P. sneebia, P. alcalifaciens, and P. burhodogranariea. These bacterial species
      that were all originally isolated as infections of wild Drosophila melanogaster
      and have been previously shown to vary in virulence to experimentally infected
      flies. RESULTS: We found that these Providencia species share a large core
      genome, but also possess distinct sets of genes that are unique to each isolate.
      We compared the genomes of these isolates to draft genomes of four Providencia
      isolated from the human gut and found that the core genome size does not
      substantially change upon inclusion of the human isolates. We found many adhesion
      related genes among those genes that were unique to each genome. We also found
      that each isolate has at least one type 3 secretion system (T3SS), a known
      virulence factor, though not all identified T3SS belong to the same family nor
      are they in syntenic genomic locations. CONCLUSIONS: The Providencia species
      examined here are characterized by high degree of genomic similarity which will
      likely extend to other species and isolates within this genus. The presence of
      T3SS islands in all of the genomes reveal that their presence is not sufficient
      to indicate virulence towards D. melanogaster, since some of the T3SS-bearing
      isolates are known to cause little mortality. The variation in adhesion genes and
      the presence of T3SSs indicates that host cell adhesion is likely an important
      aspect of Providencia virulence.

PMID- 23145769
TI  - Stitching chemically converted graphene on solid surfaces by solvent evaporation.
AB  - The suspension of chemically converted graphene (CCG) provides a cost-effective
      and facile approach to construct graphene-based materials. However, wrinkles and
      aggregates usually occur when transferring graphene from suspension to solid
      state, which significantly alter the optical, electrical, and electrochemical
      properties of deposited graphene. Our effort is devoted to the control of the
      morphology of individual graphene sheet deposited on solid surfaces by the
      solvent evaporation. Here we have studied the effects of additional components
      (e.g., organic solvent and electrolyte) in the CCG suspension on the CCG
      morphology. It was found that the CCG sheets could be stitched together and the
      graphene monolayer could be flattened by the addition of appropriate additives to
      the CCG suspension.

PMID- 23145768
TI  - Long term outcomes of pharmacological treatments for opioid dependence: does
      methadone still lead the pack?
AB  - The aim of this review was to update and summarize the scientific knowledge on
      the long term outcomes of the different pharmacological treatment options for
      opioid dependence currently available and to provide a critical discussion on the
      different treatment options based on these results. We performed a literature
      search using the PubMed databases and the reference lists of the identified
      articles. Data from research show that the three pharmacological options reviewed
      are effective treatments for opioid dependence with positive long term outcomes.
      However, each one has its specific target population and setting. While methadone
      and buprenorphine are first line options, heroin-assisted treatment is a second
      line option for those patients refractory to treatment with methadone with
      concomitant severe physical, mental, social and/or functional problems.
      Buprenorphine seems to be the best option for use in primary care offices. The
      field of opioid dependence treatment is poised to undergo a process of
      reinforcement and transformation. Further efforts from researchers, clinicians
      and authorities should be made to turn new pharmacological options into clinical
      reality and to overcome the structural and functional obstacles that maintenance
      programmes face in combatting opioid dependence. 

PMID- 23145770
TI  - Macro-level gender equality and depression in men and women in Europe.
AB  - A recurrent finding in international literature is a greater prevalence of
      depression in women than in men. While explanations for this gender gap have been
      studied extensively at the individual level, few researchers have studied macro
      level determinants of depression in men and women. In the current study we aim to
      examine the micro-macro linkage of the relationship between gender equality and
      depression by gender in Europe, using data from the European Social Survey, 2006
      2007 (N=39,891). Using a multilevel framework we find that a high degree of macro
      level gender equality is related to lower levels of depression in both women and
      men. It is also related to a smaller gender difference in depression, but only
      for certain social subgroups and only for specific dimensions of gender equality.

PMID- 23145771
TI  - Detection of Cryptosporidium species in the sea and tap water samples of Black
      Sea, Turkey.
AB  - The aim of this study was to evaluate Cryptosporidium spp. contamination of sea
      and tap water samples from Sinop and Ordu Provinces, Black Sea, Turkey. The
      samples (10 L) were collected in spring, summer, autumn, and winter in 2011. A
      total of 128 water samples was analyzed using an immunofluorescence test (IFT),
      as well as loop-mediated isothermal amplification (LAMP) and nested polymerase
      chain reaction (PCR). Cryptosporidium spp. oocysts were detected by IFT in 43 of
      the 70 samples (61.4%; 1-40 oocysts per 0.5 L) and 35 of the 58 samples (60.3%; 1
      23 oocysts per 0.5 L) in the sea water samples from Ordu and Sinop, respectively.
      The highest number of oocysts by IFT were detected in spring and winter in Ordu
      and Sinop, respectively. The results of the S-adenosylmethionine synthetase (SAM)
      gene LAMP assays were 65.5% positive for Cryptosporidium parvum , Cryptosporidium
      hominis , and Cryptosporidium meleagridis in all examined samples, while the
      SSUrRNA gene nested PCR assay was 31.0% positive. Six C. parvum nested PCR
      products from all positive samples were successfully sequenced.

PMID- 23145772
TI  - Prefrontal correlates of approach preferences for alcohol stimuli in alcohol
      dependence.
AB  - An approach bias for alcohol stimuli (i.e. faster approach than avoidance
      reactions) might facilitate relapses in alcohol dependence. Neurobiological
      models suggest hypersensitivity in the reward system [inter alia nucleus
      accumbens and orbitofrontal cortex (OFC)] to cause pathologically enhanced
      approach impulses towards alcohol stimuli. At the same time, in alcohol
      dependence, these structures are only insufficiently controlled by a hypoactive
      dorsolateral prefrontal cortex (DLPFC). The present study investigated the
      cortical aspects of this model with functional near-infrared spectroscopy in 21
      alcohol-dependent in-patients and 21 healthy controls (HC; comparable in age,
      gender and education) during performance of the Approach-Avoidance Task (AAT) for
      the first time. Complementing previous findings, in reaction times (RTs),
      patients showed stronger approach preferences for alcohol than non-alcohol
      stimuli. For non-alcohol stimuli, patients even displayed avoidance preferences.
      The reversed pattern was found in HC. Group differences in activity of the OFC
      were identical to those in RTs, revealing patients to assign higher subjective
      value to approaching alcohol stimuli. In both groups, regulatory activity in the
      right DLPFC was stronger during avoiding than approaching alcohol pictures.
      Probable awareness of the behavioural hypotheses due to explicit task
      instructions and patients' deficient prefrontal function might account for this
      equally aligned pattern. Results are discussed with regard to recent findings
      revealing a reduced behavioural approach bias and risk for relapse by applying a
      retraining version of the AAT. Functional measurements might serve as a method
      for monitoring the corresponding neurobiological changes and-possibly-predicting
      the success of such a training. 

PMID- 23145773
TI  - Structural optimization of 2,5-thiophene amides as highly potent and selective
      17beta-hydroxysteroid dehydrogenase type 2 inhibitors for the treatment of
      osteoporosis.
AB  - Inhibition of 17beta-HSD2 is an attractive mechanism for the treatment of
      osteoporosis. We report here the optimization of human 17beta-HSD2 inhibitors in
      the 2,5-thiophene amide class by varying the size of the linker (n equals 0 and
      2) between the amide moiety and the phenyl group. While none of the
      phenethylamides (n = 2) were active, most of the anilides (n = 0) turned out to
      moderately or strongly inhibit 17beta-HSD2. The four most active compounds showed
      an IC50 of around 60 nM and a very good selectivity toward 17beta-HSD1, 17beta
      HSD4, 17beta-HSD5, 11beta-HSD1, 11beta-HSD2 and the estrogen receptors alpha and
      beta. The investigated compounds inhibited monkey 17beta-HSD2 moderately, and one
      of them showed good inhibitory activity on mouse 17beta-HSD2. SAR studies allowed
      a first characterization of the human 17beta-HSD2 active site, which is predicted
      to be considerably larger than that of 17beta-HSD1.

PMID- 23145774
TI  - Doping-based stabilization of the M2 phase in free-standing VO2 nanostructures at
      room temperature.
AB  - A new high-yield method of doping VO(2) nanostructures with aluminum is proposed,
      which renders possible stabilization of the monoclinic M2 phase in free-standing
      nanoplatelets in ambient conditions and opens an opportunity for realization of a
      purely electronic Mott transition field-effect transistor without an accompanying
      structural transition. The synthesized free-standing M2-phase nanostructures are
      shown to have very high crystallinity and an extremely sharp temperature-driven
      metal-insulator transition. A combination of X-ray microdiffraction, micro-Raman
      spectroscopy, energy-dispersive X-ray spectroscopy, and four-probe electrical
      measurements allowed thorough characterization of the doped nanostructures. Light
      is shed onto some aspects of the nanostructure growth, and the temperature-doping
      level phase diagram is established.

PMID- 23145775
TI  - Reactivation of RASSF1A in breast cancer cells by curcumin.
AB  - Reactivation of tumor suppressor genes (TSGs) involved in carcinogenesis by
      nontoxic bioactive food component represents a promising strategy for cancer
      chemoprevention. Recently, curcumin has been demonstrated to inhibit a bacterial
      DNA methyltransferase (M. Sss I) activity, induce global DNA hypomethylation in
      leukemia cells, and reactivate several hypermethylation silenced genes in lung
      and prostate cancer cells. Herein, we demonstrated that curcumin can enhance the
      mRNA and protein levels of ras-association domain family protein 1A (RASSF1A), 1
      hypermethylation-silenced TSG, and decrease its promoter methylation in breast
      cancer cells. Mechanistic study demonstrated that curcumin can decrease DNA
      methylation activity of nuclear extract and downregulate the mRNA and protein
      levels of DNMT1 in MCF-7 cells, which may be associated with curcumin-induced
      disruption of NF-kappaB/Sp1 complex bound to the promoter region of DNMT1.
      Altogether, this study reveals a novel molecular mechanism of curcumin as a chemo
      preventive agent for breast cancer through hypomethylation reactivation of
      RASSF1A.

PMID- 23145777
TI  - Adherent endotoxin on dental implant surfaces: a reappraisal.
AB  - Abstract   Osteoimmunology, i.e. the cross-talk between cells from the immuno and
      skeletal systems, suggests a role of pro-inflammatory cytokines in the
      stimulation of osteoclasts activity. Endotoxin or bacterial challenges to
      inflammatory cells are directly relevant to dental implants pathologies involving
      bone resorption, such as osteointegration failure and periimplantitis. While the
      endotoxin amount on implant devices is regulated by standards, it is not known
      whether commercially available dental implants elicit different levels of
      adherent-endotoxin stimulated cytokines. The objective of this work is to develop
      a model system and to evaluate endotoxin-induced  expression of pro-inflammatory
      cytokines genes relevant to osteoclasts activation on commercially available
      dental implants. Murine J774-A1 macrophages were cultured on Ti disks with
      different level of Lipopolysaccharide (LPS) contamination,  to define the time
      course of the inflammatory response to endotoxin, as evaluated by RT-PCR
      analysis. The developed protocol was then used to measure adherent endotoxin on
      commercially available dental implants, packaged, sterile, that is in the "as
      implanted" condition. Results show that tested dental implants induce variable
      expression of endotoxin-stimulated genes, sometime over the level expected to
      promote bone resorption in vivo. Results are not affected by the specific surface
      treatment, rather they likely reflect cares in cleaning and packaging protocols.
      In conclusion, expression of genes that enhance osteoclasts activity through
      endotoxins stimulation of inflammatory cells is widely different on commercially
      available dental implants. A reappraisal of the clinical impact of adherent
      endotoxins on dental (and bone) implant devices is required on the light of
      increasing knowledge on crosstalk between cells from the immuno and skeletal
      systems.

PMID- 23145776
TI  - Rapamycin has paradoxical effects on S6 phosphorylation in rats with and without
      seizures.
AB  - PURPOSE:   Accumulating data have demonstrated that seizures induced by kainate
      (KA) or pilocarpine activate the mammalian target of rapamycin (mTOR) pathway and
      that mTOR inhibitor rapamycin can inhibit mTOR activation, which subsequently has
      potential antiepileptic effects. However, a preliminary study showed a
      paradoxical exacerbation of increased mTOR pathway activity reflected by S6
      phosphorylation when rapamycin was administrated within a short period before KA
      injection. In the present study, we examined this paradoxical effect of rapamycin
      in more detail, both in normal rats and KA-injected animals. METHODS:   Normal
      rats or KA-treated rats pretreated with rapamycin at different time intervals
      were sacrificed at various time points (1, 3, 6, 10, 15, and 24 h) after
      rapamycin administration or seizure onset for western blotting analysis.
      Phosphorylation of mTOR signaling target of Akt, mTOR, Rictor, Raptor, S6K, and
      S6 were analyzed. Seizure activity was monitored behaviorally and graded
      according to a modified Racine scale (n = 6 for each time point). Neuronal cell
      death was detected by Fluoro-Jade B staining. KEY FINDINGS:   In normal rats, we
      found that rapamycin showed the expected dose-dependent inhibition of S6
      phosphorylation 3-24 h after injection, whereas a paradoxical elevation of S6
      phosphorylation was observed 1 h after rapamycin. Similarly, pretreatment with
      rapamycin over 10 h before KA inhibited the KA seizure-induced mTOR activation.
      In contrast, rapamycin administered 1-6 h before KA caused a paradoxical increase
      in the KA seizure-induced mTOR activation. Rats pretreated with rapamycin 1 h
      prior to KA exhibited an increase in severity and duration of seizures and more
      neuronal cell death as compared to vehicle-treated groups. In contrast, rapamycin
      pretreated 10 h prior to KA had no effect on the seizures and decreased neuronal
      cell death. The paradoxical effect of rapamycin on S6 phosphorylation was
      correlated with upstream mTOR signaling and was reversed by pretreatment of
      perifosine, an Akt inhibitor. SIGNIFICANCE:   These data indicate the complexity
      of S6 regulation and its effect on epilepsy. Paradoxical effects of rapamycin
      need to be considered in clinical applications, such as for potential treatment
      for epilepsy and other neurologic disorders.

PMID- 23145778
TI  - Endoscopic biopsy of cystic intracerebral tumours.
AB  - This technical note describes the application of neuroendoscopy for decompressing
      and obtaining tissue samples from cystic intracerebral tumours. The method
      provides for visualisation of the solid tumour component prior to biopsy and
      retains the advantages of being a burr hole procedure.

PMID- 23145779
TI  - Molecular dynamics simulation study on the molecular structures of the amylin
      fibril models.
AB  - The structural characterization of amyloid fibers is one of the most investigated
      areas in structural biology. Recently, protofibril models for amylin, i.e., the
      37-residue human islet amyloid polypeptide or hIAPP were suggested by two groups
      based on NMR (Biochemistry 2007, 46, 13505-13522) and X-ray (Protein Sci. 2008,
      17, 1467-1474) techniques. However, there are significant differences in the two
      models which maybe originate from the polymorphic nature of amylin fibrils. To
      obtain further insights into the packing and stability features of the different
      models, we performed a series of molecular dynamics simulations on them. Our
      analysis showed that even pairs of beta-sheets composed of a limited number of
      beta-strands are stable in the 100-ns simulations, which suggests that steric
      zipper interactions at a beta-sheet-beta-sheet interface strongly contribute to
      the stability of these amyloid aggregates. For both models, outer strands are
      more flexible, which might coincide with the dynamical requirement that outer
      strands act as growing sites facilitating conformational changes of new incoming
      chains. Moreover, simulation results showed that the X-ray models are
      structurally more compact than the NMR models and have more intimate patterns,
      which lead to more rigid amyloid models. As a result, the X-ray models are
      energetically more stable than the NMR models. Further modeling analyses verify
      the most likely amylin fibril model among both NMR and X-ray models. Upon further
      study of the force-induced dissociation of a single chain from the protofibrils,
      the binding energy and the mechanical stability of the fibril models are
      revealed. On these bases, it is possible to reconcile the crystallographic and
      the NMR data on the basic amylin fiber unit.

PMID- 23145780
TI  - The effect of inbreeding on natural selection in a seed-feeding beetle.
AB  - Little is known about how inbreeding alters selection on ecologically relevant
      traits. Inbreeding could affect selection by changing the distribution of traits
      and/or fitness, or by changing the causal effect of traits on fitness. Here, I
      test whether selection on egg size varies with the degree of inbreeding in the
      seed-feeding beetle, Stator limbatus. There was strong directional selection
      favoring large eggs for both inbred and outbred beetles; offspring from smaller
      eggs had lower survivorship on a resistant host. Inbreeding treatment had no
      effect on the magnitude of selection on egg size; all selection coefficients were
      between ~0.078 and 0.096, regardless of treatment. However, inbreeding depression
      declined with egg size; this is because the difference in fitness between inbreds
      and outbreds did not change, but average fitness increased, with egg size. A
      consequence of this is that populations that differ in mean egg size should
      experience different magnitudes of inbreeding depression (all else being equal)
      and thus should differ in the magnitude of selection on traits that affect
      mating, simply as a consequence of variation in egg size. Also, maternal traits
      (such as egg size) that mediate stressfulness of the environment for offspring
      can mediate the severity of inbreeding depression.

PMID- 23145781
TI  - Mycotoxins in the environment: I. Production and emission from an agricultural
      test field.
AB  - Mycotoxins are secondary metabolites that are naturally produced by fungi which
      infest and contaminate agricultural crops and commodities (e.g., small grain
      cereals, fruits, vegetables, and organic soil material). Although these compounds
      have extensively been studied in food and feed, only little is known about their
      environmental fate. Therefore, we investigated over nearly two years the
      occurrence of various mycotoxins in a field cropped with winter wheat of the
      variety Levis, which was artificially inoculated with Fusarium spp., as well as
      their emission via drainage water. Mycotoxins were regularly quantified in whole
      wheat plants (0.1-133 mg/kg(dry weight), for deoxynivalenol), and drainage water
      samples (0.8 ng/L to 1.14 MUg/L, for deoxynivalenol). From the mycotoxins
      quantified in wheat (3-acetyl-deoxynivalenol, deoxynivalenol, fusarenone-X,
      nivalenol, HT-2 toxin, T-2 toxin, beauvericin, and zearalenone), only the more
      hydrophilic ones or those prevailing at high concentrations were detected in
      drainage water. Of the total amounts produced in wheat plants (min: 2.3; max: 292
      g/ha/y), 0.5-354 mg/ha/y, i.e. 0.002-0.12%, were emitted via drainage water.
      Hence, these compounds add to the complex mixture of natural and anthropogenic
      micropollutants particularly in small rural water bodies, receiving mainly runoff
      from agricultural areas.

PMID- 23145782
TI  - Trachoma in Far North Queensland: an example of poor population health practice.

PMID- 23145783
TI  - Virulence factor regulator (Vfr) controls virulence-associated phenotypes in
      Pseudomonas syringae pv. tabaci 6605 by a quorum sensing-independent mechanism.
AB  - Virulence factor regulator (Vfr) is a member of the cyclic 3',5'-adenosine
      monophosphate (cAMP) receptor proteins that regulate the expression of many
      important virulence genes in Pseudomonas aeruginosa. The role of Vfr in
      pathogenicity has not been elucidated fully in phytopathogenic bacteria. To
      investigate the function of Vfr in Pseudomonas syringae pv. tabaci 6605, the vfr
      gene was disrupted. The virulence of the vfr mutant towards host tobacco plants
      was attenuated significantly, and the intracellular cAMP level was decreased. The
      vfr mutant reduced the expression of flagella-, pili- and type III secretion
      system-related genes and the defence response in nonhost Arabidopsis leaves.
      Furthermore, the expression levels of achromobactin-related genes and the iron
      uptake ability were decreased, suggesting that Vfr regulates positively these
      virulence-related genes. In contrast, the vfr mutant showed higher tolerance to
      antimicrobial compounds as a result of the enhanced expression of the resistance
      nodulation-division family members, the mexA, mexB and oprM genes. We further
      demonstrated that the mutant strains of vfr and cyaA, an adenylate cyclase gene
      responsible for cAMP synthesis, showed a similar phenotype, suggesting that Vfr
      regulates virulence factors in a cAMP-dependent manner. Because there was no
      significant difference in the production of acylhomoserine lactone (AHL) quorum
      sensing molecules in the wild-type, vfr and cyaA mutant strains, Vfr might
      control important virulence factors by an AHL-independent mechanism in an early
      stage of infection by this bacterium.

PMID- 23145784
TI  - Rural older adults' mental health: status and challenges in care delivery.
AB  - INTRODUCTION: Health disparities remain a challenge in rural populations, with
      mental health care especially challenging as the proportion of older adults
      continues to increase worldwide. This study examined the mental health service
      needs of, and use by, independently living rural older adults, with a focus on
      depression. METHODS: Older adults (&&num;8805; 50 years) were asked to complete a
      survey. RESULTS: There were 150 respondents: 29% were between the ages of 50 and
      64 years and 71% were 65 years and older. On a composite variable, 23.3% were at
      risk for depression. One-half to two-thirds reported awareness of local mental
      health services, but nearly three-quarters never used these. Barriers to
      effective treatment of depression included stress, healthcare costs, and
      denial/fear of depression. There was an 'avoidance' factor in depression
      diagnosis and management. CONCLUSION: Older adults in rural communities
      experiencing depression pose a problem. Strategies are needed to overcome
      multiple barriers to effective diagnosis and treatment. There is a need to better
      understand the role of stress in older adults' lives. It is especially important
      for primary care providers and the local community to organize resources to allow
      for more time to be spent with older adults with mental health problems.

PMID- 23145785
TI  - The influence of surface structure on H4SiO4 oligomerization on rutile and
      amorphous TiO2 surfaces: an ATR-IR and synchrotron XPS study.
AB  - Silicic acid (H(4)SiO(4)) is ubiquitous in natural aquatic systems. Applications
      of TiO(2) in these systems will be influenced by H(4)SiO(4) sorption and
      oligomerization reactions on the TiO(2) surface, and this can affect many aspects
      of TiO(2) reactivity. The spatial arrangement of sorption sites on a metal oxide
      surface can promote specific lateral interactions, such as oligomerization,
      between sorbed species. In this work we explore the relationship between surface
      structure and interfacial H(4)SiO(4) oligomerization by quantifying the extent of
      H(4)SiO(4) sorption and oligomerization on three TiO(2) phases; a rutile phase
      having well-developed (110) faces (R180), a rutile phase with poorly developed
      (110) faces (R60), and an amorphous TiO(2) (TiO(2(am))). The in situ ATR-IR
      spectra measured over time as 0.2 mM H(4)SiO(4) reacted with TiO(2) were quite
      different on the three TiO(2) phases. The percentage of the surface H(4)SiO(4)
      that was present as oligomers increased over time on all phases, but after 20 h
      almost all H(4)SiO(4) on the R180 surface was oligomeric, while the H(4)SiO(4) on
      TiO(2(am)) was predominantly monomeric. The extent of H(4)SiO(4) oligomerization
      on R60 was intermediate. When the TiO(2) phases reacted with 1.5 mM H(4)SiO(4)
      the ATR-IR spectra showed oligomeric silicates dominating the surface of all
      three TiO(2) phases; however, after 20 h the percentage of the surface H(4)SiO(4)
      present as three-dimensional polymers was ~30, 10, and 0% on R180, R60, and
      TiO(2(am)) respectively. The Si 2s photoelectron peak binding energy (BE) and the
      H(4)SiO(4) surface coverage (Gamma(Si)) were measured by XPS over a range of
      Gamma(Si). For any given Gamma(Si) the Si 2s BE's were in the order R180 > R60 >
      TiO(2(am)). A higher Si 2s BE indicates a greater degree of silicate
      polymerization. The ATR-IR and XPS results support the existing model for
      interfacial H(4)SiO(4) oligomerization where linear trimeric silicates are formed
      by insertion of a solution H(4)SiO(4) between suitably orientated adjacent
      bidentate sorbed monomers. The TiO(2(am)) has previously been shown to consist of
      ~2 nm diameter particles with a highly disordered surface. When compared to the
      TiO(2(am)) surface, the regular arrangement of TiO(6) octahedra on the rutile
      (110) face means that sorbed H(4)SiO(4) monomers on adjacent rows of singly
      coordinated oxygen atoms are oriented so as to favor linear trimer formation.
      Higher silicate polymers can form between adjacent trimers, and this is favored
      on the rutile (110) surfaces compared to the TiO(2(am)). This is also expected on
      the basis of the arrangement of surface sites on the rutile (110) surface and
      because the high surface curvature inherent in a ~2 nm spherical TiO(2(am))
      particle would increase the spatial separation of adjacent trimers.

PMID- 23145786
TI  - Studies of the in vitro cytotoxic, antioxidant, lipase inhibitory and
      antimicrobial activities of selected Thai medicinal plants.
AB  - BACKGROUND: Traditional folk medicinal plants have recently become popular and
      are widely used for primary health care. Since Thailand has a great diversity of
      indigenous (medicinal) plant species, this research investigated 52 traditionally
      used species of Thai medicinal plants for their in vitro cytotoxic, antioxidant,
      lipase inhibitory and antimicrobial activities. METHODS: The 55 dried samples,
      derived from the medicinally used parts of the 52 plant species were sequentially
      extracted by hexane, dichloromethane, ethanol and water. These 220 extracts were
      then screened for in vitro (i) cytotoxicity against four cell lines, derived from
      human lung (A549), breast (MDA-MB-231), cervical (KB3-1) and colon (SW480)
      cancers, using the MTT cytotoxicity assay; (ii) antioxidant activity, analyzed by
      measuring the scavenging activity of DPPH radicals; (iii) lipase inhibitory
      activity, determined from the hydrolytic reaction of p-nitrophenyllaurate with
      pancreatic lipase; and (iv) antimicrobial activity against three Gram-positive
      and two Gram-negative bacteria species plus one strain of yeast using the disc
      diffusion method and determination of the minimum inhibitory concentration by the
      broth micro-dilution assay. RESULTS: The crude dichloromethane and/or ethanol
      extracts from four plant species showed an effective in vitro cytotoxic activity
      against the human cancer cell lines that was broadly similar to that of the
      specific chemotherapy drugs (etoposide, doxorubicin, vinblastine and
      oxaliplatin). In particular, this is the first report of the strong in vitro
      cytotoxic activity of Bauhinia strychnifolia vines. The tested tissue parts of
      only six plant species (Allium sativum, Cocoloba uvifera, Dolichandrone
      spathacea, Lumnitzera littorea, Sonneratia alba and Sonneratia caseolaris) showed
      promising potential antioxidant activity, whereas lipase inhibitory activity was
      only found in the ethanol extract from Coscinum fenestratum and this was weak at
      17-fold lower than Orlistat, a known lipase inhibitor. The highest antimicrobial
      activity was observed in the extracts from S. alba and S. caseolaris against
      Pseudomonas aeruginosa and Candida albicans, respectively. CONCLUSION: The Thai
      medicinal plant B. strychnifolia is first reported to exert strong in vitro
      cytotoxic activities against human cancer cell lines and warrants further
      enrichment and characterization. The broad spectrum of the biological activities
      from the studied plant extracts can be applied as the guideline for the selection
      of Thai medicinal plant species for further pharmacological and phytochemical
      investigations.

PMID- 23145787
TI  - Ras-guanine-nucleotide-releasing factors 1 and 2 interact with PLCgamma at focal
      adhesions to enable IL-1-induced Ca(2+) signalling, ERK activation and MMP-3
      expression.
AB  - IL (interleukin)-1 signalling in anchorage-dependent cells involves focal
      adhesion-restricted and Ca2+-dependent Ras and ERK (extracellular-signal
      regulated kinase) activation that leads to MMP (matrix metalloproteinase) release
      and extracellular matrix remodelling. Ras activity is regulated, in part, by the
      Ca2+-responsive Ras GRFs (guanine-nucleotide-releasing factors) 1 and 2, but the
      mechanisms that link and localize IL-1-induced Ca2+ signalling to focal adhesions
      are not defined. In the present study we characterized the role of Ras-GRF1/2 in
      Ca2+ and Ras->ERK signalling after IL-1 stimulation. By immunoprecipitation we
      found that Ras-GRF1/2 associates with PLCgamma1 (phospholipase Cgamma1). This
      association enables PLCgamma1 recruitment to focal adhesions and is required for
      Ras signalling, ERK activation and MMP-3 release downstream of IL-1 stimulation.
      Depletion of PLCgamma1 by siRNA (small interfering RNA) abolished IL-1-induced
      Ras activation and MMP-3 expression. Buffering of cytosolic Ca2+ reduced Ras
      interactions with Ras-GRF1/2 and blocked MMP-3 release. The results of the
      present study show that, in addition to their functions as Ras-exchange factors,
      Ras-GRF1 and -GRF2 may act as adaptors that bind PLCgamma1 and restrict Ca2+
      signalling to the vicinity of focal adhesions, indicating a new role for these
      GRFs that is required for IL-1 induction of the Ras->ERK pathway and MMP-3
      expression.

PMID- 23145788
TI  - Preparation and characterization of Ag-loaded SmVO4 for photocatalysis
      application.
AB  - Ag/SmVO4 composite photocatalysts were synthesized and characterized by BET, XRD,
      Raman, SEM, TEM, XPS and DRS techniques. Their photocatalytic activities were
      determined by oxidative decomposition of RhB in aqueous solution under visible
      light irradiation. The charge separation efficiency was evaluated by the
      photocurrent-time and ?OH-trapping experiments. The results revealed that the
      loaded Ag species greatly improved the efficiency in charge separation, and thus
      led to enhanced photocatalytic activities compared with that of the pure SmVO4.
      The sample contained 0.5 wt% Ag and heated at 500 degrees C presents the highest
      photoactivity.

PMID- 23145789
TI  - A systematic review of the effect of paracetamol on blood pressure in
      hypertensive and non-hypertensive subjects.
AB  - AIM: To review current evidence on the effect of paracetamol on blood pressure
      (BP), the quality of the previous studies and the validity of the results, and to
      summarize these findings. METHODS: A systematic literature review was performed
      by searching PubMed, the Cochrane library and EMBASE for publications between the
      years 1963 and 2012. RESULTS: We identified three case reports, seven prospective
      observational trials, six randomized controlled trials, one commentary and two
      reviews. Some, but not all, of the observational studies, which included over 147
      000 patients, showed an increased risk of hypertension with paracetamol use. The
      randomized studies were generally small and the results were inconsistent. Three
      studies, which included 104 patients, showed an increase of systolic BP by ~4
      mmHg, two studies, which included 27 patients, reported no change in BP and one
      study, which included 21 patients, reported a fall in BP although no placebo arm
      was included for comparison. CONCLUSIONS: The overall effect of paracetamol on BP
      is unclear. Given that paracetamol is often suggested as a safer alternative to
      non-steroidal anti-inflammatory drugs (NSAIDs), it would seem that further
      prospective evidence is now needed to address the effect of paracetamol on BP.
      This would be best done with larger studies in relevant cohorts using BP measured
      by ambulatory BP monitoring as the primary endpoint.

PMID- 23145791
TI  - A novel molecular beacon bearing a graphite nanoparticle as a nanoquencher for in
      situ mRNA detection in cancer cells.
AB  - Molecular beacons (MBs) have shown fascinating applications in many biological
      fields. However, exploration of cost-effective, sensitive, stable and efficient
      MB for in situ live cell- based assay has still room for improvement. In this
      regards, we have developed a novel MB which bears a spherical graphite
      nanoparticle (GN) as a fluorescent quencher. The GN resulted in the high
      quenching efficiency, and the presence of GN enhanced the biological stability
      and transfection of the MB into the cells, thereby enabling the real-time
      survivin mRNA detection and quantification in the MCF-7 breast cancer cells.
      These results demonstrated that the advancement of the proposed MB containing a
      GN nanoquencher can be used as a robust molecular probe for genetic analysis in
      the cells.

PMID- 23145790
TI  - Distribution and diversity of mycoplasma plasmids: lessons from cryptic genetic
      elements.
AB  - BACKGROUND: The evolution of mycoplasmas from a common ancestor with Firmicutes
      has been characterized not only by genome down-sizing but also by horizontal gene
      transfer between mycoplasma species sharing a common host. The mechanisms of
      these gene transfers remain unclear because our knowledge of the mycoplasma
      mobile genetic elements is limited. In particular, only a few plasmids have been
      described within the Mycoplasma genus. RESULTS: We have shown that several
      species of ruminant mycoplasmas carry plasmids that are members of a large family
      of elements and replicate via a rolling-circle mechanism. All plasmids were
      isolated from species that either belonged or were closely related to the
      Mycoplasma mycoides cluster; none was from the Mycoplasma bovis-Mycoplasma
      agalactiae group. Twenty one plasmids were completely sequenced, named and
      compared with each other and with the five mycoplasma plasmids previously
      reported. All plasmids share similar size and genetic organization, and present a
      mosaic structure. A peculiar case is that of the plasmid pMyBK1 from M. yeatsii;
      it is larger in size and is predicted to be mobilizable. Its origin of
      replication and replication protein were identified. In addition, pMyBK1
      derivatives were shown to replicate in various species of the M. mycoides
      cluster, and therefore hold considerable promise for developing gene vectors. The
      phylogenetic analysis of these plasmids confirms the uniqueness of pMyBK1 and
      indicates that the other mycoplasma plasmids cluster together, apart from the
      related replicons found in phytoplasmas and in species of the clade Firmicutes.
      CONCLUSIONS: Our results unraveled a totally new picture of mycoplasma plasmids.
      Although they probably play a limited role in the gene exchanges that participate
      in mycoplasma evolution, they are abundant in some species. Evidence for the
      occurrence of frequent genetic recombination strongly suggests they are
      transmitted between species sharing a common host or niche.

PMID- 23145792
TI  - Rapid protein-ligand costructures from sparse NOE data.
AB  - An efficient way to rapidly generate protein-ligand costructures based on
      solution-NMR using sparse NOE data combined with selective isotope labeling is
      presented. A docked model of the 27 kDa N-terminal ATPase domain of Hsp90 bound
      to a small molecule ligand was generated using only 21 intermolecular NOEs, which
      uniquely defined both the binding site and the orientation of the ligand. The
      approach can prove valuable for the early stages of fragment-based drug
      discovery.

PMID- 23145793
TI  - Young smokers' narratives: public health, disadvantage and structural violence.
AB  - This research article on youth smoking in disadvantaged communities is the
      product of a qualitative study to understand the issues faced by young smokers-
      and those trying not to be smokers--in such communities. Environmental factors
      and peer influence are widely recognised influences on adolescents' take-up and
      continuation of smoking but less is known about whether, what, how and why
      circumstances in disadvantaged communities affect young people's pathways towards
      and away from smoking. Focusing on a youth club in a disadvantaged neighbourhood
      in the North East of England, narratives about young people's relationships with
      tobacco provide an ethnographically rich, thick description of the experiences of
      a group that is too often easily ignored. We argue that young people are caught
      between competing domains that together exert a form of structural violence.
      These are, first, the economic and political structures that have overseen de
      industrialisation; second, the media structures that create desire for what they
      cannot afford; third the structures of international organised crime that
      conspire to provide them with the means to consume from which 'legitimate'
      structures effectively exclude them. Rather than expecting young people to comply
      with the health imperative, interventions need to bridge issues of agency and
      critical consciousness, which structural violence otherwise insidiously erodes.

PMID- 23145794
TI  - How specific are negative symptoms and cognitive impairment in schizophrenia? An
      analysis of PANSS and SCoRS.
AB  - INTRODUCTION: Interview-based scales can be used as coprimary measures to
      complement the assessment of cognitive impairment in schizophrenia. One major
      question that arises from the use of such tools is how specific they are in
      relation to other psychopathological domains. We analyse the specificity of the
      Positive and Negative Syndrome Scale (PANSS) negative subscale and the
      Schizophrenia Cognition Rating Scale (SCoRS). METHODS: We performed a principal
      component analysis (PCA) of PANSS negative subscale, rated by the interviewer,
      and SCoRS ratings from three different sources (patient, informant, and
      interviewer) in 101 patients with schizophrenia. Additionally, we correlated mean
      SCoRS ratings to PANSS negative subscale items to determine whether any PANSS
      item is particularly related to cognition. RESULTS: The PCA showed that the two
      first components, which explained approximately 40% of the total variance of the
      scales, represent the SCoRS ratings and the PANSS negative subscale ratings,
      respectively. The mean interviewer SCoRS was significantly correlated with the
      PANSS negative Item 5 (difficulty in abstract thinking) and with the mean PANSS
      negative subscale. The latter correlation was no longer significant when
      "difficulty in abstract thinking" was eliminated from PANSS negative subscale.
      CONCLUSIONS: In general, SCoRS and PANSS negative subscale scores address
      different constructs; however, the PANSS negative item "difficulty in abstract
      thinking" seems to address a cognitive dimension.

PMID- 23145795
TI  - 5-HTTLPR genotype and daily negative mood moderate the effects of sertraline on
      drinking intensity.
AB  - We previously reported moderating effects of age of onset of alcohol dependence
      (AD) and a functional polymorphism (5-HTTLPR) in the gene encoding the serotonin
      transporter protein in a sample of 134 individuals participating in a 12-week,
      placebo-controlled trial of sertraline. To understand more fully the effects seen
      in that study, we examined moderation by negative moods reported each evening,
      with nighttime drinking intensity (i.e. the number of standard drinks consumed at
      night) as the dependent variable. We found a daily anxiety * age of onset * 5
      HTTLPR polymorphism * medication interaction, which reflected a daily anxiety *
      medication group effect for early-onset individuals homozygous for the high
      expression (L') allele, but not others. Specifically, on days characterized by
      relatively high levels of anxiety, early-onset L' homozygotes receiving placebo
      reduced their drinking intensity significantly. In contrast, early-onset L'
      homozygotes treated with sertraline non-significantly increased their drinking
      intensity. These findings implicate anxiety as a key moderator of the observed
      pharmacogenetic effects. These findings have important implications because of
      the high prevalence of AD and the frequency with which SSRIs are prescribed to
      treat the disorders. 

PMID- 23145796
TI  - Nonendocytic delivery of functional engineered nanoparticles into the cytoplasm
      of live cells using a novel, high-throughput microfluidic device.
AB  - The ability to straightforwardly deliver engineered nanoparticles into the cell
      cytosol with high viability will vastly expand the range of biological
      applications. Nanoparticles could potentially be used as delivery vehicles or as
      fluorescent sensors to probe the cell. In particular, quantum dots (QDs) may be
      used to illuminate cytosolic proteins for long-term microscopy studies. Whereas
      recent advances have been successful in specifically labeling proteins with QDs
      on the cell membrane, cytosolic delivery of QDs into live cells has remained
      challenging. In this report, we demonstrate high throughput delivery of QDs into
      live cell cytoplasm using an uncomplicated microfluidic device while maintaining
      cell viabilities of 80-90%. We verify that the nanoparticle surface interacts
      with the cytosolic environment and that the QDs remain nonaggregated so that
      single QDs can be observed.

PMID- 23145797
TI  - Ether a go-go 1 silencing in combination with TRAIL overexpression has
      synergistic antitumor effects on osteosarcoma.
AB  - Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has been utilized
      for cancer therapy, but the resistance of cancer cells to TRAIL remains an
      obstacle. Ether a go-go 1 (Eag1) channel is overexpressed in a variety of cancers
      and implicated in tumor progression. However, the therapeutic potential of Eag1
      in osteosarcoma remains elusive. In this study, we generated CRAd5.TRAIL/siEag1
      adenoviral vector that permitted simultaneous knockdown of Eag1 and
      overexpression of TRAIL and investigated its antitumor effects on human
      osteosarcoma MG-63 cells. Our results showed that CRAd5.TRAIL/siEag1 induced
      growth arrest and apoptosis of MG-63 cells in a more efficient manner than
      CRAd5.TRAIL or CRAd5.siEag1, and had no effect on human osteoblastic hFOB 1.19
      cells. Furthermore, treatment of an osteosarcoma xenograft model with
      CRAd5.TRAIL/siEag1 resulted in significant tumor regression and cancer cell
      apoptosis, compared with treatment with CRAd5.TRAIL or CRAd5.siEag1. Taken
      together, our results demonstrate that CRAd5.TRAIL/siEag1 may represent an
      effective strategy for osteosarcoma gene therapy due to the synergistic antitumor
      effects of Eag1 knockdown and TRAIL overexpression.

PMID- 23145798
TI  - Delayed flow-mediated vasodilation and carotid atherosclerosis.
AB  - BACKGROUND: In a previous study, we identified temporally distinct postischaemic
      flow-mediated dilation (FMD) patterns comparing the standard clinical measurement
      time of 50s postcuff release with measurement at 2 min. The comparison revealed a
      cohort with the highest FMD at 50s (Early FMD), another cohort with the highest
      FMD at 2 min (Late FMD) and a third cohort with no FMD (Absent FMD). The aim of
      this study was to examine whether these temporally distinct FMD patterns
      associated with different degrees of carotid atherosclerosis. MATERIALS AND
      METHODS: One hundred and twenty-four free-living white subjects, participating in
      a cardio-vascular disease prevention campaign, were enrolled. FMD was measured at
      50s, 2 min and 3 min after forearm ischaemia. The intima-media thickness (IMT) of
      the common carotid artery was measured, and the artery was evaluated for the
      presence and number of carotid plaques. RESULTS: Fifty-seven subjects had Early
      FMD, 34 had Late FMD and 33 had Absent FMD. The three groups were comparable for
      age, sex and cardiovascular risk factors. The number of plaques in the carotid
      arteries, and IMT, increased progressively from Early, to Late, and to Absent FMD
      (P < 0.03), indicating that the FMD pattern is an independent predictive variable
      for IMT and carotid atherosclerosis. CONCLUSIONS: The present study demonstrates
      that temporal patterns associated with the degree of atherosclerosis of the
      carotid arteries. Patients with delayed vasodilation (Late FMD) had a higher
      degree of atherosclerosis than those with early vasodilation (Early FMD), and
      subjects with no postischaemic vasodilation (Absent FMD) had the most
      atherosclerosis.

PMID- 23145799
TI  - Transient optic nerve swelling after acute primary angle closure.

PMID- 23145801
TI  - Variable-temperature rate coefficients of proton-transfer equilibrium reaction
      C2H4 + H3O+ ? C2H5+ + H2O measured with a coaxial molecular beam radio frequency
      ring electrode ion trap.
AB  - The rate coefficients for the forward and reverse proton-transfer reactions
      C(2)H(4) + H(3)O(+) ? C(2)H(5)(+) + H(2)O are studied with respect to independent
      varied neutral molecule and ion temperatures. The measurements are performed
      using a coaxial molecular beam radio frequency ring electrode ion trap at trap
      temperatures down to 23 K and beam temperatures up to 450 K. The temperature
      dependent rate coefficients suggest that in this temperature window, the reaction
      proceeds through a statistically equilibrated complex. In order to explain the
      observed rate coefficients, a new type of reaction temperature was defined in
      these studies that considered collisional and internal (rotational and
      vibrational) degrees of freedom of both H(3)O(+) and C(2)H(4). The enthalpy and
      entropy of the equilibrium reaction deduced from a Van't Hoff plot are DeltaH =
      (5.1 +/- 0.5) kJ.mol(-1) and DeltaS = (-15.0 +/- 0.9) J.mol(-1).K(-1),
      respectively.

PMID- 23145802
TI  - Deja-vu all over again: using simulation to evaluate the impact of shorter shelf
      life for red blood cells at Hema-Quebec.
AB  - BACKGROUND: Since the 1970s red blood cells (RBCs) have had a rated shelf life of
      42 days. Recently, studies have suggested poorer patient outcomes when older
      blood is transfused. However, shortening the shelf life of RBCs may increase
      costs and lead to greater instances of outdates and shortages. STUDY DESIGN AND
      METHODS: A simulation method to evaluate the impact of a shorter shelf life for
      RBCs on a regional blood network was developed. A network model of the production
      and distribution system in the province of Quebec was built and validated.
      RESULTS: The model suggests that a shelf life of 21 or 28 days will have modest
      impact on outdate and shortage rates. A shelf life of 14 days will create
      significant challenges for both blood suppliers and hospitals and will result in
      systemwide outdate rates of 6.64% and shortage rates of 2.75%. The impact of a
      shorter shelf life for RBCs will disproportionately affect smaller and midsize
      hospitals. CONCLUSION: A shelf life of 28 or 21 days is feasible without
      excessive increases to systemwide outdate, shortage, or emergency ordering rates.
      Large hospitals will see minimal impact; smaller hospitals will see larger
      increases and may be unable to find inventory policies that maintain both low
      outdate and shortage rates. Reducing the shelf life to 14 days, or lower, results
      in significant challenges for suppliers and hospitals of all sizes. All hospitals
      will see an impact on outdate and shortage rates; overall systemwide outdate
      rates (6% or more) will reach levels that would currently be considered
      unacceptably high.

PMID- 23145803
TI  - Flapless alveolar ridge preservation utilizing the ''socket-plug'' technique:
      clinical technique and review of the literature.
AB  - Abstract   It has been documented that after every extraction of one or more
      teeth, the alveolar bone of the respective region undergoes resorption and
      atrophy. Therefore, ridge preservation techniques are often employed after tooth
      extraction to limit this phenomenon. The benefits of a flapless procedure include
      maintenance of the buccal keratinized gingiva, and prevention of alterations to
      the gingival contours and migration of the mucogingival junction that are often
      experienced after raising a flap. The purpose of this article is to review the
      literature concerning flapless ridge preservation techniques with the aid of
      collagen plugs for occlusion of the socket. The term ''socket plug technique'' is
      introduced to describe these techniques. The basic steps of the ''socket-plug
      technique'' consist of atraumatic tooth extraction, placement of the appropriate
      biomaterials in the extraction site, preservation of soft tissue architecture
      employing a flapless technique and placement and stabilization of the collagen
      plug. A case example is presented that illustrates the steps used in this
      technique.

PMID- 23145804
TI  - Change to FIT increased CRC screening rates: evaluation of a US screening
      outreach program.
AB  - OBJECTIVES: To compare completion rates of colorectal cancer screening tests
      within a health maintenance organization before and after widespread adoption of
      the fecal immunochemical test (FIT). STUDY DESIGN: Retrospective cohort study.
      METHODS: Using electronic medical records of 113,901 patients eligible for
      colorectal cancer screening, we examined test completion during 2 successive time
      periods among those who received an automated screening outreach call. The time
      periods were: 1) the "guaiac fecal occult blood test (gFOBT) era," a 15-month
      period during which only gFOBT was routinely offered, and 2) a 9-month "FIT era,"
      when only a new FIT was routinely offered. In addition to analyzing completion
      rates, we analyzed the impact of practice-level variables and patient-level
      variables on overall screening completion during the 2 different observation
      periods. RESULTS: The change from gFOBT to FIT in an integrated care delivery
      system increased the likelihood of screening completion by 7.7% overall, and the
      likelihood of screening with a fecal test by 8.9%. The greatest gains in
      screening completion using FIT were among women and elderly patients. Completion
      of FIT was not as strongly associated with medical office visits or with having a
      primary care provider as was screening with gFOBT. CONCLUSIONS: Adoption of FIT
      within an integrated care system increased completion of colon cancer screening
      tests within a 9-month assessment period, compared with a previous 15-month gFOBT
      era. Higher completion rates of the FIT may allow for more effective
      dissemination of programs to increase colorectal cancer screening through
      centralized outreach programs.

PMID- 23145805
TI  - Implementation of EHR-based strategies to improve outpatient CAD care.
AB  - OBJECTIVES: To evaluate the effects of a multifaceted quality improvement
      intervention during 2 time periods on 4 coronary artery disease [CAD] measures in
      4 primary care practices. During the first phase, electronic reminders prompted
      physicians to order indicated medications or record contraindications and
      refusals (exceptions). In the second phase, physicians also received reports
      about their performance (including lists of patients not satisfying these
      measures), and financial incentives were announced. STUDY DESIGN: Time series
      analysis. METHODS: Adult CAD patients seen within the preceding 18 months were
      included. The primary outcome was the performance on each measure (proportion of
      eligible patients satisfying each measure after removing those with exceptions).
      Secondary outcomes were the proportion with the medication on their medication
      list, and the proportion with exceptions. RESULTS: Median performance at baseline
      was 78.8% for antiplatelet treatment, 85.1% for statin treatment, 77.0% for beta
      blocker after myocardial infarction (MI), and 67.1% for angiotensinconverting
      enzyme inhibitor or angiotensin receptor blocker after MI. Performance improved
      slightly for 3 measures during the first phase and improved more substantially
      for all 4 measures during the second phase. For 3 of 4 measures, however,
      documentation of exceptions increased but not medication prescribing. Most
      exceptions were judged to be appropriate by peer review. CONCLUSIONS: Physicians
      responded more to the combination of feedback and financial incentives than they
      had to electronic reminders alone. High performance was only achieved for 1 of 4
      measures and recording of exceptions rather than increases in medication
      prescribing accounted for most of the observed improvements.

PMID- 23145806
TI  - Toward tailored disease management for type 2 diabetes.
AB  - OBJECTIVES: To assess the differentiated effects of population-based disease
      management programs (DMPs) for type 2 diabetes on intermediary clinical outcomes
      in The Netherlands. METHODS: Data covering a period from 20 to 24 months between
      January 2008 and December 2010 were collected from 18 Dutch care groups (primary
      care provider networks that have bundled payment contracts for delivery of
      diabetes DMPs). Meta-analysis and meta-regression methods were used to conduct
      differentiated analyses of these programs' effects over time on 4 clinical
      indicators: glycated hemoglobin, lowdensity lipoprotein, systolic blood pressure,
      and body mass index. Heterogeneous average results were stratified according to
      various patient and process characteristics to investigate whether differences in
      these features could explain variation in outcomes. RESULTS: Between 56% and 71%
      of patients (N = 105,056) had valid first- and second-year measurements of the
      study outcomes. Although average changes in these measures over time were small,
      stratified analyses demonstrated that clinically relevant improvements were
      achieved in patients with poor first-year health values. Interactions with age,
      disease duration, comorbidity, and smoking status were not consistent across
      outcomes; nonetheless, heterogeneity in results decreased considerably when
      simultaneously correcting for known patient characteristics. Positive effects
      tended to diminish with longer length of follow-up, while greater measurement
      frequency was associated with improved results, especially in patients with poor
      health. CONCLUSIONS: Our data suggest that tailored disease management, in which
      not only evidencebased guidelines but also patient characteristics directly
      determine care processes, including self-management support, has great potential
      to improve the cost-effectiveness of current chronic care delivery.

PMID- 23145807
TI  - Pediatric integrated delivery system's experience with pandemic influenza A
      (H1N1).
AB  - OBJECTIVE: To describe 1 pediatric integrated delivery system's experience with
      the influenza A (H1N1) pandemic in 2009 to illustrate the benefits of
      coordination, scale, scope, and flexibility in handling large volumes of patients
      in many locations. METHODS: Through multidisciplinary planning across a large,
      multisite pediatric delivery system, an effective 3-tier plan was developed to
      handle anticipated increased volumes associated with the fall 2009 influenza
      pandemic in the Philadelphia region. RESULTS: Patient demand for services
      increased to record-setting levels, particularly for emergency department visits
      and phone calls. The 3-tier plan of response allowed for graded and appropriate
      response to volumes that more than doubled in many locations. Measured by wait
      times and leftwithout- being-seen rates, the system appeared to match capacity to
      demand effectively. Lessons learned in terms of successes and challenges are
      useful for future planning. CONCLUSIONS: The experience of 1 pediatric delivery
      system in handling increased volume due to pandemic influenza may hold lessons
      for other organizations and for policy makers seeking to improve the
      preparedness, quality, and value of healthcare. These experiences do not imply
      the need for vertical integration with ownership, but do support tight
      coordination, communication, integration, and alignment in any management
      structure.

PMID- 23145808
TI  - Medicare Part D claims rejections for nursing home residents, 2006 to 2010.
AB  - OBJECTIVES: Much has been written about trends in Medicare Part D formulary
      design and consumers' choice of plans, but little is known about the magnitude of
      claims rejections or their clinical and administrative implications. Our
      objective was to study the overall rate at which Part D claims are rejected,
      whether these rates differ across plans, drugs, and medication classes, and how
      these rejection rates and reasons have evolved over time. STUDY DESIGN AND
      METHODS: We performed descriptive analyses of data on paid and rejected Part D
      claims submitted by 1 large national longterm care pharmacy from 2006 to 2010. In
      each of the 5 study years, data included approximately 450,000 Medicare
      beneficiaries living in long-term care settings with approximately 4 million Part
      D drug claims. Claims rejection rates and reasons for rejection are tabulated for
      each study year at the plan, drug, and class levels. RESULTS: Nearly 1 in 6 drug
      claims was rejected during the first 5 years of the Medicare Part D program, and
      this rate has increased over time. Rejection rates and reasons for rejection
      varied substantially across drug products and Part D plans. Moreover, the reasons
      for denials evolved over our study period. Coverage has become less of a factor
      in claims rejections than it was initially and other formulary tools such as drug
      utilization review, quantity-related coverage limits, and prior authorization are
      increasingly used to deny claims. CONCLUSIONS: Examining claims rejection rates
      can provide important supplemental information to assess plans' generosity of
      coverage and to identify potential areas of concern.

PMID- 23145810
TI  - The conserved oligomeric Golgi complex is involved in penetration resistance of
      barley to the barley powdery mildew fungus.
AB  - Membrane trafficking is vital to plant development and adaptation to the
      environment. It is suggested that post-Golgi vesicles and multivesicular bodies
      are essential for plant defence against directly penetrating fungal parasites at
      the cell wall. However, the actual plant proteins involved in membrane transport
      for defence are largely unidentified. We applied a candidate gene approach and
      single cell transient-induced gene silencing for the identification of membrane
      trafficking proteins of barley involved in the response to the fungal pathogen
      Blumeria graminis f.sp. hordei. This revealed potential components of vesicle
      tethering complexes [putative exocyst subunit HvEXO70F-like and subunits of the
      conserved oligomeric Golgi (COG) complex] and Golgi membrane trafficking
      (COPIgamma coatomer and HvYPT1-like RAB GTPase) as essential for resistance to
      fungal penetration into the host cell.

PMID- 23145809
TI  - Effect of laparoscopic splenectomy in patients with Hepatitis C and cirrhosis
      carrying IL28B minor genotype.
AB  - BACKGROUND: IL28B and ITPA genetic variants are associated with the outcome of
      pegylated-interferon and ribavirin (PEG-IFN/RBV) therapy. However, the
      significance of these genetic variants in cirrhotic patients following
      splenectomy has not been determined. METHODS: Thirty-seven patients with HCV
      induced cirrhosis who underwent laparoscopic splenectomy (Spx group) and 90 who
      did not (non-Spx group) were genotyped for IL28B and ITPA. The outcome or adverse
      effects were compared in each group. Interferon-stimulated gene 15 (ISG15) and
      protein kinase R expression in the spleen was measured using total RNA extracted
      from exenterate spleen. RESULTS: Sustained virological response (SVR) rate was
      higher in patients carrying IL28B major genotype following splenectomy (50% vs
      27.3%) and in patients carrying minor genotype in the Spx group compared to non
      Spx group (27.3% vs 3.6%, P < 0.05). Pretreatment splenic ISG expression was
      higher in patients carrying IL28B major. There was no difference in progression
      of anemia or thrombocytopenia between patients carrying each ITPA genotype in the
      Spx group. Although splenectomy did not increase hemoglobin (Hb) level, Hb
      decline tended to be greater in the non-Spx group. In contrast, splenectomy
      significantly increased platelet count (61.1 * 103/MUl vs 168.7 * 103/MUl, P <
      0.01), which was maintained during the course of PEG-IFN/RBV therapy.
      CONCLUSIONS: IL28B genetic variants correlated with response to PEG-IFN/RBV
      following splenectomy. Splenectomy improved SVR rate among patients carrying
      IL28B minor genotype and protected against anemia and thrombocytopenia during the
      course of PEG-IFN/RBV therapy regardless of ITPA genotype.

PMID- 23145811
TI  - Widespread occurrence and distribution of bisphenol A diglycidyl ether (BADGE)
      and its derivatives in human urine from the United States and China.
AB  - Despite reports of the occurrence of bisphenol A diglycidyl ether (BADGE) and its
      derivatives in canned foods and consumer products, biomonitoring studies of human
      exposure to these compounds are lacking. In this study, 127 urine samples
      collected from the U.S. and China were analyzed for free and total (free plus
      conjugated) concentrations of BADGE and its three derivatives, bisphenol A (2,3
      dihydroxypropyl) glycidyl ether [BADGE.H(2)O], bisphenol A (3-chloro-2
      hydroxypropyl) (2,3-dihydroxypropyl) ether [BADGE.HCl.H(2)O], and bisphenol A bis
      (2,3-dihydroxypropyl) ether [BADGE.2H(2)O], using high-performance liquid
      chromatography-tandem mass spectrometry (HPLC-MS/MS). BADGE and its three
      derivatives (collectively referred to as BADGEs) were found in 100% of the urine
      samples analyzed. Total urinary concentrations of BADGEs in the U.S. ranged from
      1.24 to 9.03 ng/mL, with a GM concentration of 3 ng/mL. Concentrations of BADGEs
      in urine from adults (GM: 1.36 ng/mL) and children (1.02 ng/mL) in China were 3
      fold lower than the concentrations found in the U.S. Both free and conjugated
      forms of BADGEs were present in urine, and the proportion of free form was
      inversely related to the total concentration of BADGEs. Among the four BADGEs
      measured in urine, BADGE.2H(2)O was the predominant compound, accounting for 45
      60% of the total BADGEs concentration, followed by BADGE (17-24%). The
      distribution of the four BADGEs varied, depending on age, gender, and ethnicity
      of the adults and children. Daily intake (DI) and effective daily intake (DI(E))
      of BADGEs were estimated based on urinary concentrations, and their respective
      values were 69.4 and 9.16 ng/kg-bw/day for the U.S. population and 28.4 and 5.69
      ng/kg-bw/day for the Chinese population. The concentrations of BADGEs in U.S.
      urine were 3- to 4-fold higher than the corresponding concentrations of bisphenol
      A.

PMID- 23145812
TI  - Development of a new method for identification and quantification in
      cerebrospinal fluid of malignant cells from breast carcinoma leptomeningeal
      metastasis.
AB  - BACKGROUND: The diagnosis of leptomeningeal metastasis (LM) in patients with
      solid tumors remains difficult. The usual diagnostic methods of cytomorphological
      assessment of cerebro-spinal fluid (CSF) and gadolinium enhanced MRI of the
      entire neuraxis lack both specificity and sensitivity. The Veridex CellSearch(r)
      technology has been designed for the detection of circulating tumor cells (CTC)
      in blood from cancer patients and validated for the follow-up and prognosis of
      breast, prostate, colorectal, and lung cancer. Our aim was to adapt this
      technology for the detection and the enumeration of tumor cells in the CSF of
      breast cancer patients presenting with LM. METHODS: On the occasion of a
      randomized phase III study evaluating the role of the intrathecal treatment in LM
      from breast cancer (DEPOSEIN, EudraCT N degrees : 2010-023134-23), the
      CellSearch(r) technology was adapted to direct enrichment, enumeration and
      visualization of tumor cells in 5 mL CSF samples, collected on CellSave(r)
      Preservative Tubes and analyzed within 3 days after CSF sampling. RESULTS:
      Sixteen CSF of 8 patients with primary breast cancer presenting with LM were
      studied. EpCAM+/cytokeratin + cells with typical morphology could be observed and
      enumerated sequentially with reproducible results in low or elevated numbers in 8
      patients. CONCLUSION: This methodology, established on a limited volume of sample
      and allowing delayed processing, could prove of great interest in the diagnosis
      and follow-up of cancer patients with LM, especially to appreciate the efficacy
      of chemotherapy.

PMID- 23145813
TI  - Platinum electrodeposition on unsupported carbon nano-onions.
AB  - An effort to develop smaller, well-dispersed catalytic materials
      electrochemically on high-surface-area carbon supports is required for improved
      fuel cell performance. A high-surface-area carbon material of interest is carbon
      nano-onions (CNOs), also known as multilayer fullerenes. The most convenient
      synthesis method for CNOs is annealing nanodiamond particles, thus retaining the
      size of the precursors and providing the possibility to prepare very small
      nanocatalysts using electrochemical techniques. In terms of pure metal catalysts,
      platinum is the most common catalyst used in fuel cells. The combination of Pt
      nanoparticles with CNOs could lead to new catalytic nanomaterials. In this work,
      this was accomplished by using a rotating disk-slurry electrode (RoDSE)
      technique. The Pt/CNO catalysts were prepared from slurries that contained
      functionalized CNOs and K(2)PtCl(6) as the platinum precursor in aqueous 0.1 M
      H(2)SO(4) solution. X-ray photoelectron spectroscopy results showed that 37% of
      the Pt on the CNOs is metallic Pt whereas 63% had higher binding energies, which
      is evidence of higher oxidation states or the presence of Pt atoms and clusters
      on CNOs. However, aberration-corrected scanning transmission electron microscopy
      of the Pt/CNOs confirmed the presence of Pt atoms and clusters on CNOs. Thermal
      gravimetric analysis showed the excellent thermal stability of the Pt/CNOs and a
      lower onset potential for the electrochemical oxidation of methanol compared to
      that of commercial Pt/Vulcan catalyst material. The computational method
      confirmed the Pt atoms' location at CNOs surface sites. Geometric parameters for
      distances between Pt atoms in the 3Pt/CNOs molecular system from our theoretical
      calculations are in agreement with the respective parameters obtained
      experimentally. The combination of CNO with RoDSE presents a new highly dispersed
      catalyst nanomaterial.

PMID- 23145815
TI  - The self-directed violence classification system and the columbia classification
      algorithm for suicide assessment: a crosswalk.
AB  - The lack of a standardized nomenclature for suicide-related thoughts and
      behaviors prompted the Centers for Disease Control and Prevention, with the
      Veterans Integrated Service Network 19 Mental Illness Research Education and
      Clinical Center, to create the Self-Directed Violence Classification System
      (SDVCS). SDVCS has been adopted by the Department of Veterans Affairs and the
      Department of Defense. Another classification system, the Columbia Classification
      Algorithm for Suicide Assessment, has been recommended by the Food and Drug
      Administration. To facilitate the use of both systems, this article provides a
      "crosswalk" between the two classification systems.

PMID- 23145814
TI  - Cry1Aa binding to the cadherin receptor does not require conserved amino acid
      sequences in the domain II loops.
AB  - Characterizing the binding mechanism of Bt (Bacillus thuringiensis) Cry toxin to
      the cadherin receptor is indispensable to understanding the specific insecticidal
      activity of this toxin. To this end, we constructed 30 loop mutants by randomly
      inserting four serial amino acids covering all four receptor binding loops (loops
      alpha8, 1, 2 and 3) and analysed their binding affinities for Bombyx mori
      cadherin receptors via Biacore. High binding affinities were confirmed for all 30
      mutants containing loop sequences that differed from those of wild-type.
      Insecticidal activities were confirmed in at least one mutant from loops 1, 2 and
      3, suggesting that there is no critical amino acid sequence for the binding of
      the four loops to BtR175. When two mutations at different loops were integrated
      into one molecule, no reduction in binding affinity was observed compared with
      wild-type sequences. Based on these results, we discussed the binding mechanism
      of Cry toxin to cadherin protein.

PMID- 23145816
TI  - Mimicking the intramolecular hydrogen bond: synthesis, biological evaluation, and
      molecular modeling of benzoxazines and quinazolines as potential antimalarial
      agents.
AB  - The intramolecular hydrogen bond formed between a protonated amine and a
      neighboring H-bond acceptor group in the side chain of amodiaquine and isoquine
      is thought to play an important role in their antimalarial activities. Here we
      describe isoquine-based compounds in which the intramolecular H-bond is mimicked
      by a methylene linker. The antimalarial activities of the resulting benzoxazines,
      their isosteric tetrahydroquinazoline derivatives, and febrifugine-based 1,3
      quinazolin-4-ones were examined in vitro (against  Plasmodium falciparum ) and in
      vivo (against  Plasmodium berghei ). Compounds 6b,c caused modest inhibition of
      chloroquine transport via the parasite's "chloroquine resistance transporter"
      (PfCRT) in a  Xenopus laevis  oocyte expression system. In silico predictions and
      experimental evaluation of selected drug-like properties were also performed on
      compounds 6b,c. Compound 6c emerged from this work as the most promising analogue
      of the series; it possessed low toxicity and good antimalarial activity when
      administered orally to  P. berghei -infected mice.

PMID- 23145817
TI  - Angular orientation of nanorods using nanophotonic tweezers.
AB  - Near-field optical techniques have enabled the trapping, transport, and handling
      of nanoscopic materials much smaller than what can be manipulated with
      traditional optical tweezers. Here we extend the scope of what is possible by
      demonstrating angular orientation and rotational control of both biological and
      nonbiological nanoscale rods using photonic crystal nanotweezers. In our
      experiments, single microtubules (diameter 25 nm, length 8 MUm) and multiwalled
      carbon nanotubes (outer diameter 110-170 nm, length 5 MUm) are rotated by the
      optical torque resulting from their interaction with the evanescent field
      emanating from these devices. An angular trap stiffness of kappa = 92.8
      pN.nm/rad(2).mW is demonstrated for the microtubules, and a torsional spring
      constant of 22.8 pN.nm/rad(2).mW is measured for the nanotubes. We expect that
      this new capability will facilitate the development of high precision
      nanoassembly schemes and biophysical studies of bending strains of biomolecules.

PMID- 23145818
TI  - Cooperativeness and competitiveness as two distinct constructs: validating the
      Cooperative and Competitive Personality Scale in a social dilemma context.
AB  - The present research validated the construct and criterion validities of the
      Cooperative and Competitive Personality Scale (CCPS) in a social dilemma context.
      The results from three studies supported the notion that cooperativeness and
      competitiveness are two independent dimensions, challenging the traditional view
      that they are two ends of a single continuum. First, confirmatory factor analyses
      revealed that a two-factor structure fit the data significantly better than a one
      factor structure. Moreover, cooperativeness and competitiveness were either not
      significantly correlated (Studies 1 and 3) or only moderately positively
      correlated (Study 2). Second, cooperativeness and competitiveness were
      differentially associated with Schwartz's Personal Values. These results further
      supported the idea that cooperativeness and competitiveness are two distinct
      constructs. Specifically, the individuals who were highly cooperative emphasized
      self-transcendent values (i.e., universalism and benevolence) more, whereas the
      individuals who were highly competitive emphasized self-enhancement values (i.e.,
      power and achievement) more. Finally, the CCPS, which adheres to the trait
      perspective of personality, was found to be a useful supplement to more prevalent
      social motive measures (i.e., social value orientation) in predicting cooperative
      behaviors. Specifically, in Study 2, when social value orientation was controlled
      for, the CCPS significantly predicted cooperative behaviors in a public goods
      dilemma (individuals who score higher on cooperativeness scale contributed more
      to the public goods). In Study 3, when social value orientation was controlled
      for, the CCPS significantly predicted cooperative behaviors in commons dilemmas
      (individuals who score higher on cooperativeness scale requested fewer resources
      from the common resource pool). The practical implications of the CCPS in
      conflict resolution, as well as in recruitment and selection settings, are
      discussed. 

PMID- 23145820
TI  - A simple method for quantification of peptides and proteins by matrix-assisted
      laser desorption ionization mass spectrometry.
AB  - Even though matrix-assisted laser desorption ionization (MALDI) is a powerful
      technique for mass spectrometry of peptides and proteins, it is not quite useful
      for their quantification that is one of the outstanding problems in quantitative
      proteomics. The main difficulty lies in the poor reproducibility of MALDI
      spectra. In this work, a simple method to circumvent this problem has been
      developed. The method is based on a previous observation that the reaction
      quotient for the matrix-to-peptide proton transfer evaluated in temperature
      selected MALDI was nearly constant regardless of the peptide concentration in the
      solid sample. This implied a direct proportionality between the relative
      abundance of an analyte ion in a temperature-selected MALDI spectrum and the
      concentration of the corresponding neutral in the solid sample. This relation has
      been confirmed by calibration curves obtained for some peptides. Another
      characteristic of the relation is that it holds even when other analytes are
      present. This has been demonstrated for mixtures containing peptides and
      proteins. This and the fact that the method does not require the addition of
      internal standards allow rapid and inexpensive quantification of any analyte
      amenable to MALDI.

PMID- 23145819
TI  - New aspects of the phosphatase VHZ revealed by a high-resolution structure with
      vanadate and substrate screening.
AB  - The recently discovered 150-residue human VHZ (VH1-related protein, Z member) is
      one of the smallest protein tyrosine phosphatases (PTPs) known and contains only
      the minimal structural elements common to all PTPs. We report a substrate
      screening analysis and a crystal structure of the VHZ complex with vanadate at
      1.1 A resolution, with a detailed structural comparison with other members of the
      protein tyrosine phosphatase family, including classical tyrosine-specific
      protein tyrosine phosphatases (PTPs) and dual-specificity phosphatases (DSPs). A
      screen with 360 phosphorylated peptides shows VHZ efficiently catalyzes the
      hydrolysis of phosphotyrosine (pY)-containing peptides but exhibits no activity
      toward phosphoserine (pS) or phosphothreonine (pT) peptides. The new structure
      reveals a deep and narrow active site more typical of the classical tyrosine
      specific PTPs. Despite the high degrees of structural and sequence similarity
      between VHZ and classical PTPs, its general acid IPD-loop is most likely
      conformationally rigid, in contrast to the flexible WPD counterpart of classical
      PTPs. VHZ also lacks substrate recognition domains and other domains typically
      found on classical PTPs. It is therefore proposed that VHZ is more properly
      classified as an atypical PTP rather than an atypical DSP, as has been suggested.

PMID- 23145821
TI  - Interventions guided by analysis of quality indicators decrease the frequency of
      laryngospasm during pediatric anesthesia.
AB  - INTRODUCTION: Clinical outcomes in pediatric anesthesia have improved
      significantly over the last 20-30 years but unexpected laryngospasm that is
      difficult to treat can still result in patient morbidity, increased postoperative
      medical management and unnecessary hospital admission. The incidence of
      laryngospasm in pediatric anesthesia is difficult to determine with incidences
      from 0.9% to as high as 14% quoted in the literature. Clinical experience in our
      institution suggests that laryngospasm is one of the more frequent unanticipated
      complications that occur under general anesthesia. Therefore, we applied quality
      improvement (QI) methodology to: (i) identify the etiology and contributing
      factors that lead to unanticipated incidents during pediatric anesthesia care;
      and (ii) decrease the incidence of laryngospasm during pediatric anesthesia care
      by focusing on awareness, preparedness, education and knowledge translation.
      MATERIALS & METHODS: We conducted a 30-month improvement project. Twelve months
      of baseline data describing unanticipated events during pediatric anesthesia care
      were collected prospectively in a single institution. Data were analyzed to
      identify leading causes of these unanticipated events and to identify key drivers
      to improve overall quality of care. Interventions focused on raising awareness of
      the impact of laryngospasm on quality of patient care, knowledge dissemination
      and the creation of a knowledge translation tool to encourage future early
      learning. The primary objective was to decrease the incidence of unanticipated
      calls for help due to laryngospasm by 50% over a 12-month period. RESULTS: During
      the 12-month baseline data period, laryngospasm was responsible for 33 instances
      (50%) of the 65 'calls for help' identified. The incidence of laryngospasm for
      which help was sought was 0.25% of all anesthetics performed during the baseline
      data period. After the introduction of our interventions, 16 (24%) of the 68
      'calls for help' over the subsequent 16 months were attributed to laryngospasm.
      The incidence of laryngospasm for which help was sought during the second time
      period was 0.09% of all anesthetics performed. CONCLUSIONS: We applied QI
      methodology to identify potential improvements in the quality of anesthesia care
      we deliver to our patients. By designing a number of key drivers and
      interventions specifically focused on laryngospasm, we decreased the incidence of
      unanticipated calls for help due to laryngospasm by 50% and maintained this
      improvement to clinical care across a 12-month period.

PMID- 23145822
TI  - The study of protein-protein interactions in bacteria.
AB  - Many of the functions fulfilled by proteins in the cell require specific protein
      protein interactions (PPI). During the last decade, the use of high-throughput
      experimental technologies, primarily based on the yeast 2-hybrid system,
      generated extensive data currently located in public databases. This information
      has been used to build interaction networks for different species. Unfortunately,
      due to the nature of the yeast 2-hybrid system, these databases contain many
      false positives and negatives, thus they require purging. A method for confirming
      these PPI is to test them using a technique that operates in vivo and detects
      binary PPI. This article comprises an overview of the study of PPI and describes
      the main techniques that have been used to identify bacterial PPI, prioritizing
      those that can be used for their verification, and it also mentions a number of
      PPI that have been identified or confirmed using these methods.

PMID- 23145823
TI  - Construction of recombinant lactobacilli expressing the core neutralizing epitope
      (COE) of porcine epidemic diarrhea virus and a fusion protein consisting of COE
      and  Escherichia coli  heat-labile enterotoxin B, and comparison of the immune
      responses by orogastric immunization.
AB  - The core neutralizing epitope (COE) region of porcine epidemic diarrhea virus
      (PEDV) plays an important role in the development of the subunit vaccine against
      PEDV infection. To enhance the vaccine's immunogenicity,  Escherichia coli  heat
      labile enterotoxin B (LTB) has usually been adopted as a molecular adjuvant. In
      this study, the COE and LTB-COE genes were engineered into the  Lactobacillus 
      Escherichia coli shuttle vectors pSAPG1 (surface-displaying) and pSAPG2
      (secreting) followed by electrotransformation into  Lactobacillus casei  (Lc) to
      yield the following recombinant strains: Lc:PG1-LTB-COE, Lc:PG2-LTB-COE, Lc:PG1
      COE, and Lc:PG2-COE. Our results showed that mice immunized orogastrically with
      L. casei expressing COE or LTB-COE produced secretory immunoglobulin A and
      immunoglobulin G with the ability to neutralize PEDV in sera and mucus. Moreover,
      higher levels of interleukin-4 and gamma interferon were also exhibited compared
      with negative control. These data displayed the tendency of Lc:PG2-LTB-COE >
      Lc:PG1-LTB-COE > Lc:PG2-COE > Lc:PG1-COE at the same time point. Taken together,
      LTB-COE is more suitable for Lactobacillus expressing system to engineer mucosal
      vaccine against PEDV infection.

PMID- 23145824
TI  - Caenorhabditis elegans avoids staphylococcal superantigenic toxins via 5
      hydroxytryptamine-dependent pathway.
AB  - Avoidance behavior of Caenorhabditis elegans, a nematode, towards Staphylococcus
      aureus, a pathogenic bacterium, was studied. Caenorhabditis elegans avoided S.
      aureus cultures and also their culture supernatants, suggesting that secretory
      molecules are involved in the repellent activity. We demonstrated that toxic
      shock syndrome toxin 1 (TSST-1) and staphylococcal enterotoxin C (SEC), the
      superantigenic toxins produced by S. aureus, are responsible for the nematode
      avoidance. By using TSST-1 and SEC mutants, the results indicated that the
      repellent activity of these toxins is independent of their superantigenic
      activity. The TSST-1 and SEC were found to locate at chemosensory neurons that
      are responsible for the recognition of repellents and avoidance of pathogenic
      bacteria. When mutants of C. elegans deficient in Toll/interleukin-1 receptor
      (TIR-1) and 5-hydroxytryptamine (5-HT) biosynthesis were used, avoidance behavior
      was attenuated. In the 5-HT biosynthesis deficient mutant nematodes, the
      avoidance activity was recovered when exogenous 5-HT was added. tph-1 expression
      and 5-HT production were upregulated when the nematodes were treated with TSST-1
      or SEC. These results suggest that C. elegans avoids S. aureus by recognizing
      secretory molecules including TSST-1 and SEC and this avoidance is dependent on
      TIR and production of 5-HT.

PMID- 23145825
TI  - Pulsed-field gel electrophoresis typing, antibiotic resistance, and plasmid
      profiles of Escherichia coli strains isolated from foods.
AB  - Bacterial contamination in foods and antimicrobial resistance levels of common
      pathogenic strains causing food-borne disease are important in human health.
      Thus, typing technologies are important tools to determine primary sources of
      bacterial contamination. In this study, 40 Escherichia coli strains isolated from
      85 food samples were evaluated in terms of genetic diversity, susceptibility to
      certain antibiotics, and plasmid profiles. Pulsed-field gel electrophoresis was
      used to identify the genetic relations of E. coli isolates. It was determined
      that the 40 E. coli strains revealed 32 different pulsotypes represented by 6
      subtypes. Antibiotic susceptibility tests conducted by using a disc diffusion
      method against 15 antibiotics showed that although the isolates revealed 14
      different types of resistance profiles, the strains showed the greatest
      resistance to ampicillin (77.5%), followed by ticarcillin-clavulanic acid (30%),
      tetracycline (22.5%), and cephalothin (14.5%). Plasmid isolations studies of the
      strains conducted by the method of alkaline lysis revealed that 18 (45%) of 40 E.
      coli strains contain 31 different plasmid bands ranging between 64.4 and 1 kb.
      The results showed that PFGE was a powerful method in tracking sources of food
      contamination and that the antibiotic resistance levels of food isolates were
      high and should be monitored.

PMID- 23145826
TI  - Molecular mechanisms of antimicrobial resistance in fecal Escherichia coli of
      healthy dogs after enrofloxacin or amoxicillin administration.
AB  - Escherichia coli respond to selective pressure of antimicrobial therapy by
      developing resistance through a variety of mechanisms. The purpose of this study
      was to characterize the genetic mechanisms of antimicrobial resistance in fecal
      E. coli after the routine use of 2 popular antimicrobials. Fourteen resistant E.
      coli isolates, representing predominant clones that emerged in healthy dogs'
      feces after treatment with either amoxicillin (11 E. coli isolates) or
      enrofloxacin (3 E. coli isolates), were tested for mutations in DNA gyrase (gyrA
      and gyrB) and in topoisomerase IV (parC) and for the presence of beta-lactamases
      (bla(TEM), bla(SHV), bla(PSE-1) and bla(CTX-M)) and plasmid-mediated quinolone
      resistance (qnrA, qnrB, qnrS, aac(6')-Ib, and qepA), by polymerase chain
      reaction. Escherichia coli isolates cultured following amoxicillin therapy only
      expressed single-drug resistance to beta-lactams, while the isolates cultured
      from dogs receiving enrofloxacin therapy expressed multidrug resistance (MDR).
      The use of RND efflux pump inhibitors increased the susceptibility of the 3 MDR
      E. coli isolates to doxycycline, chloramphenicol, enrofloxacin, and
      ciprofloxacin, which indicates a role of the efflux pump in the acquisition of
      the MDR phenotype. Amplification and sequencing of AcrAB efflux pump regulators
      (soxR, soxS, marR, and acrR) revealed only the presence of a single mutation in
      soxS in the 3 MDR isolates.

PMID- 23145827
TI  - phoR sequences as a phylogenetic marker to differentiate the species in the
      Bacillus subtilis group.
AB  - Bacillus subtilis and its closely related species are indistinguishable from one
      another by morphological characteristics and 16S rDNA sequences. In this study,
      the partial phoR sequence was tested to determine the phylogenetic relationship
      of species in the B. subtilis group. Degenerate primers were developed according
      to the relatively conserved nucleotide sequences of phoR and the linked gene phoP
      in the B. subtilis group. The primers amplified a 1100 bp phoR fragment from
      strains representative of 6 species in the B. subtilis group. Based on the
      sequenced fragments, 26 type strains comprising these 6 species were clearly
      distinguished. At the intraspecies level, the phoR sequence similarities were 90%
      100%, but at the interspecies level, the phoR sequence similarities were 32.8%
      75%. Compared with the gyrB sequence, the phoR sequences showed a larger
      divergence especially at the interspecies levels. Therefore, the phoR sequence
      may be an efficient alternative marker for phylogenetic and taxonomic analysis of
      species in the B. subtilis group. Twenty-three Bacillus undomesticated isolates
      were tested for identification and phylogenetic analysis based on the phoR and
      gyrB sequences. The 23 isolates could be clearly delineated into 4 distinct
      groups, 10 as B. subtilis, 3 as B. mojavensis, 2 as B. atrophaeus, and 8 as B.
      amyloliquefaciens.

PMID- 23145828
TI  - Characterization of the type III secretion associated low calcium response genes
      of Vibrio parahaemolyticus RIMD2210633.
AB  - Vibrio parahaemolyticus is a significant human pathogen associated with
      gastroenteritis. Two V. parahaemolyticus type 3 secretion systems, T3SS-1 and
      T3SS-2, secrete effector proteins and have been implicated in host-cell
      cytotoxicity and enterotoxicity, respectively. Vibrio parahaemolyticus T3SS-1
      substrates have been identified, although many predicted substrates (based on
      homologies) remain undetected in secreted fractions and therefore
      uncharacterized. We have experimentally developed and optimized a secretion assay
      protocol allowing for reliable and reproducible detection of V. parahaemolyticus
      T3SS-1 secreted proteins within culture supernatants. The presence of magnesium
      and absence of calcium were critical factors in promoting type III secretion of
      protein substrates. Proteomic approaches identified known V. parahaemolyticus
      secreted effectors in addition to previously unidentified proteins. Isogenic
      mutants in putative low calcium response genes were generated, and experiments
      further implicated the genes in secretion and V. parahaemolyticus-mediated host
      cell cytotoxicity during infection. These approaches should be valuable towards
      future detailed genetic and biochemical analyses of T3SS-1 in V.
      parahaemolyticus.

PMID- 23145829
TI  - Effects of remediation on the bacterial community of an acid mine drainage
      impacted stream.
AB  - Acid mine drainage (AMD) represents a global threat to water resources, and as
      such, remediation of AMD-impacted streams is a common practice. During this
      study, we examined bacterial community structure and environmental conditions in
      a low-order AMD-impacted stream before, during, and after remediation. Bacterial
      community structure was examined via polymerase chain reaction amplification of
      16S rRNA genes followed by denaturing gradient gel electrophoresis. Also,
      bacterial abundance and physicochemical data (including metal concentrations)
      were collected and relationships to bacterial community structure were determined
      using BIO-ENV analysis. Remediation of the study stream altered environmental
      conditions, including pH and concentrations of some metals, and consequently, the
      bacterial community changed. However, remediation did not necessarily restore the
      stream to conditions found in the unimpacted reference stream; for example,
      bacterial abundances and concentrations of some elements, such as sulfur,
      magnesium, and manganese, were different in the remediated stream than in the
      reference stream. BIO-ENV analysis revealed that changes in pH and iron
      concentration, associated with remediation, primarily explained temporal
      alterations in bacterial community structure. Although the sites sampled in the
      remediated stream were in relatively close proximity to each other, spatial
      variation in community composition suggests that differences in local
      environmental conditions may have large impacts on the microbial assemblage.

PMID- 23145830
TI  - On not airing our dirty laundry: Intergroup contexts suppress ingroup criticism
      among strongly identified group members.
AB  - Not every situation affords the appropriate setting to articulate group problems,
      and I predicted that strongly identified members would be particularly sensitive
      to the intergroup context in which ingroup criticism is expressed. In Study 1,
      strongly but not weakly identified members reduced criticism of their ingroup
      when communicating with an outgroup (vs. ingroup) audience, and this effect was
      mediated by concerns for the reputation of the group. In Study 2, heightening the
      salience of intergroup competition suppressed criticism among group members high
      (but not low) in the solidarity component of identification, even though they
      were communicating with an ingroup audience. These findings show that even when
      criticizing their group, strongly identified members are attuned to the
      collective interest: they are more willing to articulate problems to an insider
      than when asked to do so by an outgroup member or when reminded of a competitive
      intergroup dynamic. 

PMID- 23145831
TI  - Characterization of the cellular immunity in patients presenting extensive
      dermatophytoses due to Trichophyton rubrum.
AB  - Dermatophytes invade the stratum corneum of the skin and other keratinized
      tissues such as hair and nails, and Trichophyton rubrum causes approximately 80%
      of cutaneous mycoses in humans. To evaluate the cellular immune response of
      patients with extensive dermatophytosis caused by T. rubrum, we evaluated
      lymphocyte populations, the lymphoproliferative response to: phytohaemagglutinin
      (PHA); anti-CD3 (OKT3); and pokeweed mitogen (PWM), Candida sp. (CMA), an extract
      of T. rubrum, and the main fungal epitope TriR2 (T). We also evaluated
      interleukin (IL)-4, IL-10, IL-12 and IFN-gamma after stimulation by PHA, CMA and
      TriR2. The immunophenotyping showed no differences between patients and controls.
      The lymphoproliferation test showed significant differences between the groups
      stimulated by PWM and CMA, as well as against TriR2, being significantly higher
      for the control group. Conversely, there were similar results for the groups
      after stimulation by the extract. The cytokines' quantification showed a
      significant difference between the groups only for IFN-gamma stimulated by PHA
      and TriR2. We can conclude that the fungal extract can stimulate
      lymphoproliferation by both groups' lymphocytes. However, the response to Tri r2
      was more specific. We showed that some patients with extensive dermatophytosis
      have normal cellular response, recognising both the extract and TriR2.

PMID- 23145832
TI  - Effect of sea-level rise on salt water intrusion near a coastal well field in
      southeastern Florida.
AB  - A variable-density groundwater flow and dispersive solute transport model was
      developed for the shallow coastal aquifer system near a municipal supply well
      field in southeastern Florida. The model was calibrated for a 105-year period
      (1900 to 2005). An analysis with the model suggests that well-field withdrawals
      were the dominant cause of salt water intrusion near the well field, and that
      historical sea-level rise, which is similar to lower-bound projections of future
      sea-level rise, exacerbated the extent of salt water intrusion. Average 2005
      hydrologic conditions were used for 100-year sensitivity simulations aimed at
      quantifying the effect of projected rises in sea level on fresh coastal
      groundwater resources near the well field. Use of average 2005 hydrologic
      conditions and a constant sea level result in total dissolved solids (TDS)
      concentration of the well field exceeding drinking water standards after 70
      years. When sea-level rise is included in the simulations, drinking water
      standards are exceeded 10 to 21 years earlier, depending on the specified rate of
      sea-level rise. 

PMID- 23145833
TI  - A universal measure of chaotropicity and kosmotropicity.
AB  - Diverse parameters, including chaotropicity, can limit the function of cellular
      systems and thereby determine the extent of Earth's biosphere. Whereas parameters
      such as temperature, hydrophobicity, pressure, pH, Hofmeister effects, and water
      activity can be quantified via standard scales of measurement, the chao
      /kosmotropic activities of environmentally ubiquitous substances have no widely
      accepted, universal scale. We developed an assay to determine and quantify chao
      /kosmotropicity for 97 chemically diverse substances that can be universally
      applied to all solutes. This scale is numerically continuous for the solutes
      assayed (from +361 kJ kg(-1)  mol(-1) for chaotropes to -659 kJ kg(-1)  mol(-1)
      for kosmotropes) but there are key points that delineate (i) chaotropic from
      kosmotropic substances (i.e. chaotropes >= +4; kosmotropes <= -4 kJ kg(-1)  mol(
      1) ); and (ii) chaotropic solutes that are readily water-soluble (log P < 1.9)
      from hydrophobic substances that exert their chaotropic activity, by proxy, from
      within the hydrophobic domains of macromolecular systems (log P > 1.9). Examples
      of chao-/kosmotropicity values are, for chaotropes: phenol +143, CaCl(2) +92.2,
      MgCl(2) +54.0, butanol +37.4, guanidine hydrochloride +31.9, urea +16.6, glycerol
      [> 6.5 M] +6.34, ethanol +5.93, fructose +4.56; for kosmotropes: proline -5.76,
      sucrose -6.92, dimethylsulphoxide (DMSO) -9.72, mannitol -6.69, trehalose -10.6,
      NaCl -11.0, glycine -14.2, ammonium sulfate -66.9, polyethylene glycol- (PEG
      )1000 -126; and for relatively neutral solutes: methanol, +3.12, ethylene glycol
      +1.66, glucose +1.19, glycerol [< 5 M] +1.06, maltose -1.43 (kJ kg(-1)  mol(-1)).
      The data obtained correlate with solute interactions with, and structure-function
      changes in, enzymes and membranes. We discuss the implications for diverse fields
      including microbial ecology, biotechnology and astrobiology.

PMID- 23145834
TI  - Heliox non-invasive ventilation for preventing extubation failure in preterm
      infants.
AB  - OBJECTIVES: Our aim was to assess whether non-invasive ventilation with heliox
      may decrease the incidence of extubation failure in preterm infants with RDS.
      METHODS: Infants <29 weeks of gestation were treated immediately after extubation
      with heliox combined with nasal continuous airway pressure (Hx-NCPAP) or bilevel
      NCPAP (Hx-BiPAP) for 24 h, while infants in the control groups were treated with
      conventional NCPAP or BiPAP. The primary endpoint was the comparison of the
      extubation failure rate in the two groups, where failure was defined as the need
      for MV during the 24 h following extubation. RESULTS: Eighteen infants were
      assigned to the heliox group and 18 to the control group. The extubation failure
      rate was similar (p = 0.249) in the heliox (n = 6; 33%) and in the control group
      (n = 9; 50%), but required mean airway pressure (MAP: 4.0+1.0 vs. 4.8+1.2 cm H2O;
      p = 0.037) and PaCO2 (39+8 mmHg vs. 52+7 mmHg; p < 0.001) at 24 h of treatment
      were lower in the heliox group. CONCLUSIONS: Non-invasive ventilation with heliox
      was not effective in decreasing extubation failure in preterm infants with RDS,
      but did improve their respiratory function. Our findings might support the
      planning of large randomized controlled studies to evaluate the effectiveness of
      heliox non-invasive ventilation for decreasing extubation failure in premature
      infants.

PMID- 23145835
TI  - Multi-edge X-ray absorption spectroscopy. 1. X-ray absorption near-edge structure
      analysis of a biomimetic model of FeFe-hydrogenase.
AB  - In this work, we demonstrate the potential of multi-edge X-ray absorption near
      edge structure (XANES) analysis in completely defining the ground state
      electronic structure of a prototypical biomimetic complex of the [2Fe]-subcluster
      of the catalytic H-cluster of FeFe-hydrogenase. The spectral features at the
      ionization thresholds for Fe, S, C, and O 1s (K-edge) and Fe 2p (L-edge) core
      electrons were considered simultaneously to obtain the atomic compositions of the
      unoccupied frontier molecular orbitals. A systematic error analysis was carried
      out at the most informative S K-edge for spectra collected by multiple detection
      methods, at various data collection temperatures, and different sample
      preparation protocols. As expected for the difference in bonding between bridging
      and terminal Fe-S(thiolate) coordination, the Fe-S bond is more covalent in the
      [2Fe]-biomimetic complex with formally iron(I) centers (36 +/- 2% S character per
      Fe-S bond) than in the previously described [2Fe-2S] clusters (25 +/- 3% S
      character per Fe-S bond) with formally iron(III) centers. An electron hole-based
      analysis of the pre-edge features at Fe K-, Fe L-, and S K-edges experimentally
      defines the composition of the first three frontier unoccupied molecular orbitals
      to contain 4% Fe 4p, 44% Fe 3d, and 24% S 3p contributions per electron hole,
      respectively. The complementary CO ligand contribution thus can be defined as 28%
      per electron hole. These experimental orbital covalency values are important in
      rationalizing redox properties, electrophilicity of the metals, or
      nucleophilicity of the ligands, and critically evaluating the absolute accuracy
      of electronic structure calculations.

PMID- 23145837
TI  - Modification Of Maxillary Sinus Floor With Orthodontic Treatment and  Implant
      Therapy: A Case Letter.
AB  - Abstract   Abstract: Modification of sinus floor and providing adequate space for
      implant surgery by orthodontic tooth movement might be a predictable treatment
      procedure. In this case, implant therapy was performed by providing adequate
      space with orthodontic tooth movement in a patient has inadequate alveol height
      at posterior maxilla.Method: A 54 years old male chronic periodontitis patient
      was diagnosed with controlled type 2 diabetes. He has inadequate alveol height
      for implant surgery in posterior maxilla. After phase I periodontal therapy,
      orthodontic treatment was designed. Dental implants were placed 6 months after
      orthodontic treatment by providing adequate space. Prosthetic restorations were
      made after dental implants were osseointegrated. Shortened occlusion was planned
      in this patient. The patient was followed for 2 years postoperatively. There
      wasn't any complication after dental implants were placed. No remarkable clinical
      or radiographic changes were observed around implants during 2 years
      postoperatively.Modification of sinus floor by orthodontic treatment may be an
      alternative treatment modality in patients needing sinus lifting procedure
      resulting from pneumatization of maxillary sinus.

PMID- 23145836
TI  - Are gastric cancer resection margin proteomic profiles more similar to those from
      controls or tumors?
AB  - A strategy for treating cancer is to surgically remove the tumor together with a
      portion of apparently healthy tissue surrounding it, the so-called "resection
      margin", to minimize recurrence. Here, we investigate whether the proteomic
      profiles from biopsies of gastric cancer resection margins are indeed more
      similar to those from healthy tissue than from cancer biopsies. To this end, we
      analyzed biopsies using an offline MudPIT shotgun proteomic approach and
      performed label-free quantitation through a distributed normalized spectral
      abundance factor approach adapted for extracted ion chromatograms (XICs). A
      multidimensional scaling analysis revealed that each of those tissue-types is
      very distinct from each other. The resection margin presented several proteins
      previously correlated with cancer, but also other overexpressed proteins that may
      be related to tumor nourishment and metastasis, such as collagen alpha-1,
      ceruloplasmin, calpastatin, and E-cadherin. We argue that the resection margin
      plays a key role in Paget's "soil to seed" hypothesis, that is, that cancer cells
      require a special microenvironment to nourish and that understanding it could
      ultimately lead to more effective treatments.

PMID- 23145838
TI  - Babesia microti seroprevalence in Minnesota blood donors.
AB  - BACKGROUND: The increasing frequency of transfusion-transmitted babesiosis
      represents a concern for the safety of the US blood supply. The agent responsible
      for the disease, the intraerythrocytic parasite Babesia microti, is naturally
      transmitted to humans by a tick bite and is endemic in areas of the Northeast and
      Upper Midwest United States. In this study, we explored B. microti seroprevalence
      in blood donors from different areas of Minnesota (MN). STUDY DESIGN AND METHODS:
      We tested 2150 blood donors in MN for the presence of antibodies against B.
      microti using an immunofluorescent assay (IFA). Donors identified as positive
      (>=64) were also tested by real-time polymerase chain reaction (PCR) for the
      presence of parasite DNA. Seropositive donors were contacted by phone and asked
      questions regarding tick exposure. Donors positive by IFA were indefinitely
      deferred from donating blood. RESULTS: A total of 2150 donations were tested
      between October 2010 and November 2011. Forty-two donors (2.0%) were positive by
      IFA and one was also PCR positive. All positive donors reported extended outdoor
      activities, 12 recalled finding ticks on their body, and six had flu-like
      symptoms since their last blood draw. CONCLUSIONS: This study provides new data
      about B. microti seroprevalence in MN blood donors. Possibly because the targeted
      collection areas were mostly expected to be endemic for the parasite, the
      observed seroprevalence levels were higher than expected, although the geographic
      distribution of positive donors did not completely overlap with the distribution
      of reported clinical cases in MN.

PMID- 23145839
TI  - Systematic classification of vertebrate chemokines based on conserved synteny and
      evolutionary history.
AB  - The genes involved in host defences are known to undergo rapid evolution.
      Therefore, it is often difficult to assign orthologs in multigene families among
      various vertebrate species. Chemokines are a large family of small cytokines that
      orchestrate cell migration in health and disease. Herein, we have surveyed the
      genomes of 18 representative vertebrate species for chemokine genes and
      identified a total of 553 genes. We have determined their orthologous
      relationships and classified them in accordance with the current systematic
      chemokine nomenclature system. Our study reveals an interesting evolutionary
      history that gave origin and diversification to the vertebrate chemokine
      superfamily.

PMID- 23145840
TI  - Characteristics of student preparedness for clinical learning: clinical educator
      perspectives using the Delphi approach.
AB  - BACKGROUND: During clinical placements, clinical educators facilitate student
      learning. Previous research has defined the skills, attitudes and practices that
      pertain to an ideal clinical educator. However, less attention has been paid to
      the role of student readiness in terms of foundational knowledge and attitudes at
      the commencement of practice education. Therefore, the aim of this study was to
      ascertain clinical educators' views on the characteristics that they perceive
      demonstrate that a student is well prepared for clinical learning. METHODS: A two
      round on-line Delphi study was conducted. The first questionnaire was emailed to
      a total of 636 expert clinical educators from the disciplines of occupational
      therapy, physiotherapy and speech pathology. Expert clinical educators were asked
      to describe the key characteristics that indicate a student is prepared for a
      clinical placement and ready to learn. Open-ended responses received from the
      first round were subject to a thematic analysis and resulted in six themes with
      62 characteristics. In the second round, participants were asked to rate each
      characteristic on a 7 point Likert Scale. RESULTS: A total of 258 (40.56%)
      responded to the first round of the Delphi survey while 161 clinical educators
      completed the second (62.40% retention rate). Consensus was reached on 57
      characteristics (six themes) using a cut off of greater than 70% positive
      respondents and an interquartile deviation IQD of equal or less than 1.
      CONCLUSIONS: This study identified 57 characteristics (six themes) perceived by
      clinical educators as indicators of a student who is prepared and ready for
      clinical learning. A list of characteristics relating to behaviours has been
      compiled and could be provided to students to aid their preparation for clinical
      learning and to universities to incorporate within curricula. In addition, the
      list provides a platform for discussions by professional bodies about the role of
      placement education.

PMID- 23145842
TI  - Reply: To PMID 23171234.

PMID- 23145841
TI  - Serum parameters in the spectrum of coeliac disease: beyond standard antibody
      testing--a cohort study.
AB  - BACKGROUND: Invasive techniques are still required to distinguish between
      uncomplicated and complicated forms of CD. METHODS: We set out to investigate the
      potential use of novel serum parameters, including IL-6, IL-8, IL-17, IL-22,
      sCD25, sCD27, granzyme-B, sMICA and sCTLA-4 in patients diagnosed with active CD,
      CD on a GFD, Refractory coeliac disease (RCD) type I and II, and enteropathy
      associated T-cell lymphoma (EATL). RESULTS: In both active CD and RCDI-II
      elevated levels of the proinflammatory IL-8, IL-17 and sCD25 were observed. In
      addition, RCDII patients displayed higher serum levels of soluble granzyme-B and
      IL-6 in comparison to active CD patients. In contrast, no differences between
      RCDI and active CD or RCDII were observed. Furthermore, EATL patients displayed
      higher levels of IL-6 as compared to all other groups. CONCLUSIONS: A series of
      novel serum parameters reveal distinctive immunological characteristics of RCDII
      and EATL in comparison to uncomplicated CD and RCDI.

PMID- 23145843
TI  - Implication of the stereoisomers of ginsenoside derivatives in the
      antiproliferative effect of HSC-T6 cells.
AB  - Two ginsenoside derivatives (9, 10) along with 10 known ginsenosides (1-8, 11,
      and 12) were isolated from BST204, which is a crude ginseng extract fermented by
      enzyme and acid hydrolysis. The two ginsenosides were determined as
      12beta,20(S),25-trihydroxydammara-3-O-beta-D-glucopyranoside (9) and
      12beta,20(R),25-trihydroxydammara-3-O-beta-D-glucopyranoside (10). Compounds 1-12
      were categorized into stereoisomeric pairs differentiated by R- or S
      configuration at C-20, the number or position of sugar residues at C-3 or C-6,
      and the type of derivative at C-21. Their structure-activity relationship was
      evaluated by the cell viability assay using HSC-T6 cells. Results showed that
      20(S) (3 > 4, 7 > 8, and 9 > 10), a 2-hydroxy-2-methylbutyl moiety at C-21 (3, 7
      > 9), and the number of sugar residues at C-3 (3 > 7) significantly affected the
      antiproliferative activity on HSC-T6 cells. The inhibition of the cell
      proliferation of compound 3 was assessed by annexin-V/PI staining analysis using
      flow cytometry.

PMID- 23145844
TI  - Identification of and intervention to address therapeutic gaps in care.
AB  - OBJECTIVES: To determine if therapeutic gap identification, notification of
      community pharmacists, and intervention results in increased gap closure, reduced
      gap closure time, and fewer adherence gaps reopening. STUDY DESIGN: Prospective,
      controlled, clusterrandomized study. METHODS: State of Illinois employees and
      beneficiaries of State health plans filling prescriptions at independently owned
      community pharmacies were included. For selected chronic conditions and
      medications, gaps in medication adherence and omitted essential therapies were
      identified from prescription claims and sent as alerts for resolution with the
      patient and/or physician. Adherence and omission gap closure at 90 days were
      analyzed with Kaplan-Meier (KM) survival curve approach and Cox proportional
      hazards models including covariates. RESULTS: A total of 1433 intervention and
      1181 control adherence gaps were identified, while 677 intervention and 534
      control omission gaps were generated. Pharmacists intervened on 639 (44.6%)
      adherence and 506 (74.7%) omission gaps. Gaps were closed more often in
      intervention than control at 30 days (55.5% in intervention vs 50.6% in control),
      45 days (61.1% vs 58.4%, respectively), 60 days (66.1% vs 65.2%, respectively),
      and 90 days (73.0% vs 72.9%, respectively; adjusted hazard ratio [HR] = 1.242; P
      = .022; 95% confidence interval [CI] 1.115-1.385). Adherence gaps reopened less
      frequently in the intervention group (HR = 0.863; P = .012; 95% CI 0.769-0.968).
      A total of 89 (13.1%) intervention and 29 (5.4%) control omission gaps closed
      within 90 days (adjusted HR = 1.770; P = .005; 95% CI 1.182-2.653). CONCLUSIONS:
      Independent community pharmacists reduced gaps in care and had fewer reopened
      adherence gaps, suggesting improvement in adherence. A continuation study will
      examine the impact of the program on long-term adherence.

PMID- 23145845
TI  - EMR-based medication adherence metric markedly enhances identification of
      nonadherent patients.
AB  - OBJECTIVES: To determine whether addition of written-prescription data to
      existing adherence measures improves identification of nonadherent patients and
      prediction of changes in low-density lipoprotein (LDL) cholesterol. STUDY DESIGN:
      Retrospective database analysis of all health plan members prescribed a statin in
      2008 and followed through 2010. METHODS: We examined statin use in a 4
      millionmember health plan with 100% electronic medical record coverage. A novel
      type of medication possession ratio (MPR), integrating prescribed with dispensed
      medication data, was developed. This measure, MPRp, was compared with a standard
      dispensed-only adherence measure, MPRd. Adherence below 20% was considered
      nonadherence. The 2 adherence measures were compared regarding (1) the number of
      patients identified as nonadherent, (2) percent changes in LDL from study
      enrollment to study termination, and (3) receiver-operator curves assessing the
      association between adherence and a 24% decrease in LDL. RESULTS: A total of
      67,517 patients received 1,386,270 written prescriptions over the 3-year period.
      MPRp identified 93% more patients as nonadherent than did MPRd (P <.001). These
      newly identified patients exhibited minimal LDL decreases over the course of the
      study. Adherence by MPRp was more strongly associated with decreases in LDL than
      was adherence by MPRd (area under the curve 0.815 vs 0.770; P <.001). During the
      study period, 18.2% of patients did not fill any prescriptions and were thus
      unidentifiable by dispensed-only measures. CONCLUSIONS: Addition of written
      prescription data to adherence measures identified nearly twice the number of
      nonadherent patients and markedly improved prediction of changes in LDL.

PMID- 23145846
TI  - Financial incentives and physician commitment to guideline-recommended
      hypertension management.
AB  - OBJECTIVES: To examine the impact of financial incentives on physician goal
      commitment to guideline-recommended hypertension care. STUDY DESIGN: Clinic-level
      cluster-randomized trial with 4 arms: individual, group, or combined incentives,
      and control. METHODS: A total of 83 full-time primary care physicians at 12
      Veterans Affairs medical centers completed web-based surveys measuring their goal
      commitment to guideline-recommended hypertension care every 4 months and
      telephone interviews at months 8 and 16. Intervention arm participants received
      performance-based incentives every 4 months for 5 periods. All participants
      received guideline education at baseline and audit and feedback every 4 months.
      RESULTS: Physician goal commitment did not vary over time or across arms.
      Participants reported patient nonadherence was a perceived barrier and consistent
      follow-up was a perceived facilitator to successful hypertension care, suggesting
      that providers may perceive hypertension management as more of a patient
      responsibility (external locus of control). CONCLUSIONS: Financial incentives may
      constitute an insufficiently strong intervention to influence goal commitment
      when providers attribute performance to external forces beyond their control.

PMID- 23145847
TI  - Identifying frail older people using predictive modeling.
AB  - OBJECTIVES: To determine whether a designation of frailty using the Adjusted
      Clinical Groups-diagnoses based computerized predictive model (ACG Dx-PM) can
      identify an elderly population who (1) have the clinical characteristics of
      frailty and (2) are frail as determined by the validated Vulnerable Elders Survey
      (VES), and to determine the ability of these tools to predict adverse outcomes.
      STUDY DESIGN: Secondary analysis of administrative and survey data. METHODS:
      Participants over age 65 years (n = 195) in an outpatient comprehensive geriatric
      assessment study at an Israeli health maintenance organization (HMO) were
      screened for frailty using the ACG Dx-PM and VES. Administrative and demographic
      data were also gathered. RESULTS: Compared with ACG nonfrail patients, ACG frail
      patients were older and less likely to be married; had a higher rate of falls,
      incontinence, and need for personal care; and had a poorer quality of life
      consistent with a clinical picture of frailty. The ACG frailty tag identified a
      frail population using the VES frailty determination as the accepted standard
      with moderate success (area under the curve 0.62). Adjusting for sex and
      functional status in backward logistic regression, the ACG frailty tag predicted
      hospitalizations (P <.032) and the VES frailty tool predicted emergency
      department visits (P <.016). CONCLUSIONS: The ACG frailty tag identified an
      elderly population with clinical characteristics of frailty and performed with
      moderate success compared with the VES. Both tools predicted adverse outcomes in
      older HMO members. A combined screening approach for frailty using predictive
      modeling with a function-based survey deserves further study.

PMID- 23145848
TI  - Application of new method for evaluating performance of fracture risk tool.

PMID- 23145849
TI  - Gender difference of childhood overweight and obesity in predicting the risk of
      incident asthma: a systematic review and meta-analysis.
AB  - The aims of our meta-analysis were (i) to quantify the predictability of
      childhood overweight and obesity on the risk of incident asthma; and (ii) to
      evaluate the gender difference on this relationship. The selection criteria
      included prospective cohort paediatric studies which use age- and sex-specific
      body mass index (BMI) as a measure of childhood overweight and the primary
      outcome of incident asthma. A total of 1,027 studies were initially identified
      through online database searches, and finally 6 studies met the inclusion
      criteria. The combined result of reported relative risk from the 6 included
      studies revealed that overweight children conferred increased risks of incident
      asthma as compared with non-overweight children (relative risk, 1.19; 95%
      confidence interval [CI], 1.03-1.37). The relationship was further elevated for
      obesity vs. non-obesity (relative risk, 2.02; 95% CI, 1.16-3.50). A dose
      responsiveness of elevated BMI on asthma incidence was observed (P for trend,
      0.004). Obese boys had a significantly larger effect than obese girls (relative
      risk, boys: 2.47; 95% CI, 1.57-3.87; girls: 1.25; 95% CI, 0.51-3.03), with
      significant dose-dependent effect. Proposed mechanisms of gender difference could
      be through pulmonary mechanics, sleep disordered breathing and leptin. Further
      research might be needed to better understand the exact mechanism of gender
      difference on the obesity-asthma relationship.

PMID- 23145850
TI  - Effects of macromolecular crowding on burst phase kinetics of cytochrome c
      folding.
AB  - Excluded volume and viscosity effects of crowding agents that mimic crowded
      conditions in vivo on "classical" burst phase folding kinetics of cytochrome c
      are assessed in vitro. Upon electron transfer-triggered folding of reduced
      cytochrome c, far-UV time-resolved circular dichroism (TRCD) is used to monitor
      folding under different conditions. Earlier work has shown that folding of
      reduced cytochrome c from the guanidinium hydrochloride-induced unfolded ensemble
      in dilute phosphate buffer involves kinetic partitioning: one fraction of
      molecules folds rapidly, on a time scale identical to that of reduction, while
      the remaining population folds more slowly. In the presence of 220 mg/mL dextran
      70, a synthetic macromolecular crowding agent that occupies space but does not
      interact with proteins, the population of the fast folding step for cytochrome c
      is greatly reduced. Increasing the viscosity with sucrose to the same
      microviscosity exhibited by the dextran solution showed no significant decrease
      in the amplitude of the fast-folding phase of cytochrome c. Experiments show that
      the unfolded-state heme ligation remains bis-His in the presence of dextran 70,
      but coarse-grained simulations suggest that the unfolded-state ensemble becomes
      more compact in the presence of crowders. We conclude that excluded volume
      effects alter unfolded cytochrome c such that access to fast-folding
      conformations is reduced.

PMID- 23145851
TI  - A truncated manganese spinel cathode for excellent power and lifetime in lithium
      ion batteries.
AB  - Spinel-structured lithium manganese oxide (LiMn(2)O(4)) cathodes have been
      successfully commercialized for various lithium battery applications and are
      among the strongest candidates for emerging large-scale applications. Despite its
      various advantages including high power capability, however, LiMn(2)O(4)
      chronically suffers from limited cycle life, originating from well-known Mn
      dissolution. An ironical feature with the Mn dissolution is that the surface
      orientations supporting Li diffusion and thus the power performance are
      especially vulnerable to the Mn dissolution, making both high power and long
      lifetime very difficult to achieve simultaneously. In this investigation, we
      address this contradictory issue of LiMn(2)O(4) by developing a truncated
      octahedral structure in which most surfaces are aligned to the crystalline
      orientations with minimal Mn dissolution, while a small portion of the structure
      is truncated along the orientations to support Li diffusion and thus facilitate
      high discharge rate capabilities. When compared to control structures with much
      smaller dimensions, the truncated octahedral structure as large as 500 nm
      exhibits better performance in both discharge rate performance and cycle life,
      thus resolving the previously conflicting aspects of LiMn(2)O(4).

PMID- 23145852
TI  - Influence of surface oxygen on the interactions of carbon nanotubes with natural
      organic matter.
AB  - The sorption properties of natural organic matter (NOM) with oxidized multiwalled
      carbon nanotubes (O-MWCNTs) in simple electrolytes has been studied, as well as
      the effect that NOM concentration, pH, and O-MWCNT surface chemistry have on CNT
      stability under environmentally relevant conditions. As O-MWCNT oxygen content
      increased, NOM sorption decreased in simple electrolytes for a common set of
      solution conditions. For each O-MWCNT, NOM sorption increased with increasing
      ionic strength and decreasing pH, although the sensitivity of NOM sorption to
      these water quality parameters increased as the O-MWCNT oxygen content increased.
      Collectively, these observations indicate that NOM sorption by O-MWCNTs is
      determined by favorable hydrophobic pi-pi interactions that are moderated by
      repulsive electrostatic forces between negatively charged carboxylic acid
      functional groups on the O-MWCNTs and NOM. Stability studies conducted in
      artificial groundwater revealed that CNT stability is influenced by both the NOM
      concentration and pH, but stability was largely independent of the O-MWCNT oxygen
      concentration. These findings contrast with the marked effect that surface oxygen
      has on CNT stability in simple electrolytes. Electrophoretic mobility
      measurements revealed that the stabilizing effects of adsorbed NOM are due to the
      introduction of steric repulsion between NOM-coated CNTs, rather than from
      changes to surface charge.

PMID- 23145853
TI  - A novel flow cytometric assay for rapid detection of extended-spectrum beta
      lactamases.
AB  - The rapid detection of extended-spectrum beta-lactamases (ESBLs) is a challenge
      for most clinical microbiology laboratories because inaccurate identification of
      ESBL producers has important clinical implications for both antibiotic treatment
      and infection control. The aim of our study was to develop a rapid detection
      assay of ESBL producers based upon flow cytometric analysis. Antimicrobial
      susceptibility testing followed by molecular characterization of bla(TEM) ,
      bla(SHV) or bla(CTX-M) genes was performed on clinical isolates (41 ESBL positive
      and 20 ESBL negative) and isolates expressing well-characterized beta-lactamases,
      including ESBLs (n = 13), plasmid AmpCs (n = 3), oxacillinases (n = 5) and
      carbapenemases (n = 3). Additionally, two ATCC strains recommended by CLSI for
      susceptibility testing were used as controls. The flow cytometry analysis
      protocol involved an incubation of bacterial cells with different concentrations
      of ceftazidime (1, 2 and 4 mg/L) and cefotaxime (4, 8 and 16 mg/L) for 1 and 2
      hours, in the presence and absence of clavulanic acid; subsequently, cells were
      stained with the fluorescent dye Bis-(1,3-dibutylbarbituric acid) trimethine
      oxonol [DiBAC(4) (3)], a lipophilic anion able to diffuse across depolarized
      membranes. Additionally, CFU counts were performed. Susceptible isolates
      displayed increased fluorescence after 1 hour of incubation; conversely, the
      increase of the depolarized population was only observed after incubation with
      clavulanic acid associated with ceftazidime or cefotaxime in ESBL producers. An
      excellent correlation was obtained between the number of non-depolarized bacteria
      quantified by flow cytometry and by conventional CFU assays. A novel, accurate
      and fast flow cytometric assay is available to detect the presence of ESBLs.

PMID- 23145854
TI  - Principles and applications of halogen bonding in medicinal chemistry and
      chemical biology.
AB  - Halogen bonding has been known in material science for decades, but until
      recently, halogen bonds in protein-ligand interactions were largely the result of
      serendipitous discovery rather than rational design. In this Perspective, we
      provide insights into the phenomenon of halogen bonding, with special focus on
      its role in drug discovery. We summarize the theoretical background defining its
      strength and directionality, provide a systematic analysis of its occurrence and
      interaction geometries in protein-ligand complexes, and give recent examples
      where halogen bonding has been successfully harnessed for lead identification and
      optimization. In light of these data, we discuss the potential and limitations of
      exploiting halogen bonds for molecular recognition and rational drug design. 

PMID- 23145855
TI  - Size does matter: how to control organization of organic dyes in aqueous
      environment using specific ion effects.
AB  - Understanding the role played by external factors on the organization of
      molecules has the potential to contribute greatly to fundamental research and
      applications in fields as diverse as nanotechnology, medicine, material
      chemistry, etc. Countless studies involve the organization of small organic
      molecules in environments rich in ionic species, yet their participation in
      molecular organization is often overlooked. Herein, we critically assess the
      organization in aqueous solution of the cationic cyanine dye, thiazole orange, in
      the presence of different monovalent sodium salts. Our findings clearly indicate
      that not all ions are identical with regards to the organization of thiazole
      orange molecules and specific ions effects are at play. The conventional Debye
      and Huckel model is not sufficient to explain our results, and the participation
      of ionic species in molecular organization is explained in terms of the recent
      theory of water matching affinity. Herein, by choosing the right counterion with
      the appropriate size, we have shown that it is possible to either induce a simple
      shift in the monomer-dimer equilibrium of thiazole orange or to turn on the
      formation of larger organized structures.

PMID- 23145856
TI  - Orbitofrontal dysfunction and medication overuse in patients with migraine.
AB  - OBJECTIVE: Orbitofrontal cortex (OFC) dysfunction and poor decision making have
      been described in patients with chronic migraine and medication overuse. These
      neurobiological underpinnings might explain dependency-like behaviors often
      described in this condition, such as loss of control over painkillers, high rates
      of relapse after detoxification, and compromised social functioning. We
      investigate whether the OFC impairment was a persistent trait in migraine,
      independent of clinical and affective features, a dynamic result of the need to
      cope with the increased pain and disability, or a temporary consequence of
      medication overuse. METHODS: For this purpose, we compared 40 chronic migraineurs
      with medication overuse, 40 episodic migraineurs, and 40 matched healthy
      controls. The examination consisted of a clinical interview, Anxiety and
      Depression Hamilton Scales, Severity of Dependence Scale, and Migraine Disability
      Assessment questionnaire. A neuropsychological assessment of orbitofrontal
      function was made through the Iowa Gambling Task (IGT). Chronic migraineurs with
      medication overuse were followed for a year after detoxification. RESULTS: We
      found an impaired decision-making performance among chronic and episodic
      migraineurs that seems independent of the patients' clinical and affective
      status. Contrary to the psychiatric and clinical improvement shown 1 year after
      the detox, CM patients exhibited a persistent IGT deficit. No significant
      differences in OFC functioning were found between the CM patients who relapsed
      into medication overuse after detox and those who did not. CONCLUSIONS: The
      present findings suggest the presence of a persistent OFC dysfunction in migraine
      as a psychobiologic trait that is not influenced by the presence of medication
      overuse, the clinical severity of the disease, or the patient's affective status.
      Further studies are needed to elucidate the etiopathological role of OFC in
      migraine and medication overuse.

PMID- 23145857
TI  - Efficacy and toxicity of capecitabine-based chemotherapy in patients with
      metastatic or advanced breast cancer: results from ten randomized trials.
AB  - OBJECTIVE: The efficacy and adverse effects of capecitabine-based chemotherapy
      versus other regimens reported in previous trials were discordant. The aim of the
      present study was to determine the efficacy and toxicity profiles of capecitabine
      based chemotherapy versus capecitabine-free regimens in patients with metastatic
      and/or advanced breast cancer. METHODS: Randomized trials in which capecitabine
      based chemotherapy was compared with capecitabine-free chemotherapy were included
      by searching the PubMed database. Differences in efficacy and grade 3-4
      toxicities between capecitabine-based chemotherapy and other chemotherapy were
      compared. RESULTS: Ten randomized controlled trials were included in our meta
      analysis. Compared to patients treated with capecitabine-free chemotherapy,
      patients treated with capecitabine-based chemotherapy did not have a
      significantly different complete response (odds ratio (OR): 1.25, 95% confidence
      interval (CI): 0.87-1.79, p = 0.231), partial response (OR: 1.16, 95% CI: 0.95
      1.41, p = 0.147), and overall response (OR: 1.21, 95% CI: 1.00-1.47, p = 0.053).
      Compared to the capecitabine-free group, less hematological toxicity and more
      gastrointestinal toxicity occurred in patients treated with capecitabine-based
      chemotherapy, including neutropenia (OR: 0.34, 95% CI: 0.19-0.59, p <0.001),
      anemia (OR: 0.41, 95% CI: 0.20-0.85, p = 0.016), leukocytopenia (OR: 0.50, 95%
      CI: 0.32-0.78, p = 0.002), and diarrhea (OR: 2.35, 95% CI: 1.62-3.42, p < 0.001).
      Furthermore, patients in the capecitabine group exhibited a significantly higher
      rate of grade 3 hand-foot syndrome than the capecitabine-free group (OR: 25.16,
      95% CI: 12.27-51.58, p < 0.001). CONCLUSIONS: The present study suggests that
      capecitabine-based chemotherapy is as effective as capecitabine-free chemotherapy
      in patients with metastatic and/or advanced breast cancer with different toxicity
      profiles. Capecitabine-based chemotherapy may be better tolerated than
      capecitabine-free chemotherapy. Due to several limitations in our study, future
      large randomized trials are needed.

PMID- 23145858
TI  - Major depressive disorder severity and the frequency of painful physical
      symptoms: a pooled analysis of observational studies.
AB  - OBJECTIVE: This retrospective post-hoc analysis of observational studies assesses
      the frequency of painful physical symptoms (PPS) in patients with major
      depressive disorder (MDD) of varied severity as may be seen in clinical practice.
      METHODS: Observational studies of MDD that collected a clinician-reported measure
      of depression severity and included assessment of PPS were screened for this
      individual patient-level analysis. Six observational studies were included that
      enrolled outpatients with a diagnosis of MDD (assessed using the 17-item Hamilton
      depression scale, Hospital Anxiety and Depression Scale-Depression, or Inventory
      of Depressive Symptomatology). Measures of PPS were based on the original study
      assessment (modified Somatic Symptom Inventory [SSI] and Visual Analogue Scale
      [VAS]). Patients were divided into analysis cohorts based on the presence or
      absence of PPS. To model PPS status, odds ratios were calculated from logistic
      regression for cross-sectional analysis (main analysis) and generalized linear
      mixed models for longitudinal models (exploratory longitudinal analysis).
      RESULTS: For the main analysis, four studies (N = 2943, 71.6% female, mean age
      45.3 years) were identified. Of 2901 eligible patients, 61.7% were classified as
      having painful physical symptoms (PPS+). At study entry, 73.1% (957/1309) of
      patients in the severe category of depression, 56.8% (537/945) of those with
      moderate depression, and 45.6% (295/647) of those with mild depression were PPS+.
      The exploratory longitudinal analysis was performed using a subset (N = 2430)
      from the studies used in the main analysis plus two others (an additional 7984
      patients, 6742 of which were modeled). The likelihood of patients that were PPS-
      at baseline later developing PPS was 5% to 13% greater for patients with
      increased depression severity (P < 0.001) and the likelihood of PPS+ patients
      later not having PPS was 9% to 17% less for patients with increased depression
      severity (P < 0.0001). CONCLUSIONS: Since this is a retrospective aggregate
      analysis of several observational studies, and due to missing data, care should
      be taken in the interpretation of these results. Despite the use of adjustment
      techniques, selection bias and unmeasured confounding may still be an issue for
      comparative analysis as not all variables were collected for all studies. For
      patients treated in typical care settings, PPS were associated with depression
      severity. However, patients with mild and moderate depression also exhibited PPS.
      Clinicians should be aware that PPS are present, and may warrant treatment,
      across depression severities.

PMID- 23145859
TI  - Efficacy and safety of ceftazidime-avibactam versus imipenem-cilastatin in the
      treatment of complicated urinary tract infections, including acute
      pyelonephritis, in hospitalized adults: results of a prospective, investigator
      blinded, randomized study.
AB  - OBJECTIVES: The aim of this prospective phase II, randomized, investigator
      blinded study (NCT00690378) was to compare the efficacy and safety of ceftazidime
      avibactam and imipenem-cilastatin in hospitalized adults with serious complicated
      urinary tract infection (cUTI) due to Gram-negative pathogens. PATIENTS AND
      METHODS: Patients aged between 18 and 90 years with cUTI were enrolled and
      stratified by infection type (acute pyelonephritis or other cUTI) and randomized
      1:1 to receive intravenous ceftazidime 500 mg plus avibactam 125 mg every 8 hours
      or imipenem-cilastatin 500 mg every 6 hours. Patients meeting pre-specified
      improvement criteria after 4 days could be switched to oral ciprofloxacin.
      Patients were treated for a total of 7-14 days. The primary efficacy objective
      was a favorable microbiological response at the test-of-cure (TOC) visit 5-9 days
      post-therapy in microbiologically evaluable (ME) patients. RESULTS: Overall, 135
      patients received study therapy (safety population); 62 were included in the ME
      population (ceftazidime-avibactam, n = 27; imipenem-cilastatin, n = 35). The
      predominant uropathogen was Escherichia coli. Favorable microbiological response
      was achieved in 70.4% of ME patients receiving ceftazidime-avibactam and 71.4%
      receiving imipenem-cilastatin at the TOC visit (observed difference -1.1% [95%
      CI: -27.2%, 25.0%]). Among ME patients with ceftazidime-resistant uropathogens,
      response was observed in 6/7 (85.7%) receiving ceftazidime-avibactam. Adverse
      events were observed in 67.6% and 76.1% of patients receiving ceftazidime
      avibactam and imipenem-cilastatin, respectively. Limitations of the study include
      the small number of patients in the ME population. CONCLUSION: The results
      suggest that the efficacy and safety of ceftazidime-avibactam may be similar to
      that of imipenem-cilastatin.

PMID- 23145860
TI  - Novel acid resistance genes from the metagenome of the Tinto River, an extremely
      acidic environment.
AB  - Microorganisms that thrive in acidic environments are endowed with specialized
      molecular mechanisms to survive under this extremely harsh condition. In this
      work, we performed functional screening of six metagenomic libraries from
      planktonic and rhizosphere microbial communities of the Tinto River, an extremely
      acidic environment, to identify genes involved in acid resistance. This approach
      has revealed 15 different genes conferring acid resistance to Escherichia coli,
      most of which encoding putative proteins of unknown function or previously
      described proteins not known to be related to acid resistance. Moreover, we were
      able to assign function to one unknown and three hypothetical proteins. Among the
      recovered genes were the ClpXP protease, the transcriptional repressor LexA and
      nucleic acid-binding proteins such as an RNA-binding protein, HU and Dps.
      Furthermore, nine of the retrieved genes were cloned and expressed in Pseudomonas
      putida and Bacillus subtilis and, remarkably, most of them were able to expand
      the capability of these bacteria to survive under severe acid stress. From this
      set of genes, four presented a broad-host range as they enhance the acid
      resistance of the three different organisms tested. These results expand our
      knowledge about the different strategies used by microorganisms to survive under
      extremely acid conditions.

PMID- 23145861
TI  - Solid phase detection of C4d-fixing HLA antibodies to predict rejection in high
      immunological risk kidney transplant recipients.
AB  - Protocols for recipient desensitization may allow for successful kidney
      transplantation across major immunological barriers. Desensitized recipients,
      however, still face a considerable risk of antibody-mediated rejection (AMR),
      which underscores the need for risk stratification tools to individually tailor
      treatment. Here, we investigated whether solid phase detection of complement
      fixing donor-specific antibodies (DSA) has the potential to improve AMR
      prediction in high-risk transplants. The study included 68 sensitized recipients
      of deceased donor kidney allografts who underwent peritransplant immunoadsorption
      for alloantibody depletion (median cytotoxic panel reactivity: 73%; crossmatch
      conversion: n = 21). Pre and post-transplant sera were subjected to detection of
      DSA-triggered C4d deposition ([C4d]DSA) applying single-antigen bead (SAB)
      technology. While standard crossmatch and [IgG]SAB testing failed to predict
      outcomes in our desensitized patients, detection of preformed [C4d]DSA (n = 44)
      was tightly associated with C4d-positive AMR [36% vs. 8%, P = 0.01; binary
      logistic regression: odds ratio: 10.1 (95% confidence interval: 1.6-64.2), P =
      0.01]. Moreover, long-term death-censored graft survival tended to be worse among
      [C4d]DSA-positive recipients (P = 0.07). There were no associations with C4d
      negative AMR or cellular rejection. [C4d]DSA detected 6 months post
      transplantation were not related to clinical outcomes. Our data suggest that
      pretransplant SAB-based detection of complement-fixing DSA may be a valuable tool
      for risk stratification.

PMID- 23145862
TI  - Metabolic response to oral microcystin-LR exposure in the rat by NMR-based
      metabonomic study.
AB  - Microcystin-LR (MCLR), a potent hepatotoxin, is causing increased risks to public
      health. Although the liver is the main target organ of MCLR, the metabolic
      profiling of liver in response to MCLR in vivo remains unknown. Here, we
      comprehensively analyzed the metabolic change of liver and ileal flushes in rat
      orally gavaged with MCLR by 1H nuclear magnetic resonance (NMR). Quantification
      of hepatic MCLR and its glutathione and cysteine conjugates by liquid
      chromatography-electrospray ionization-mass spectrometry (LC-ESI-MS) was
      conducted. Metabonomics results revealed significant associations of MCLR-induced
      disruption of hepatic metabolisms with inhibition of nutrient absorption, as
      evidenced by a severe decrease of 12 amino acids in the liver and their
      corresponding elevation in ileal flushes. The hepatic metabolism signature of
      MCLR was characterized by significant inhibition of tyrosine anabolism and
      catabolism, three disrupted pathways of choline metabolism, glutathione
      exhaustion, and disturbed nucleotide synthesis. Notably, substantial alterations
      of hepatic metabolism were observable even at the low MCLR-treated group (0.04
      mg/kg MCLR), although no apparent histological changes in liver were observed in
      the low- and medium-dosed groups. These observations offered novel insights into
      the microcystin hepatotoxic mechanism at a functional level, thereby facilitating
      further assessment and clarification of human health risk from MCs exposure.

PMID- 23145863
TI  - Clinical implications of serous retinal detachment in branch retinal vein
      occlusion and response after primary intravitreal bevacizumab injection.
AB  - PURPOSE: To evaluate the impact of macular serous retinal detachment (SRD) and
      its relationship to treatment outcome after primary intravitreal bevacizumab
      (IVB) injection in patients with branch retinal vein occlusion (BRVO) and macular
      edema (ME). METHODS: Seventy-three patients with ME secondary to BRVO who
      received primary IVB (2.5 mg/0.1 mL) were included in this study. The specific ME
      patterns were investigated using optical coherence tomography (OCT) examination.
      Visual acuity (VA), central macular thickness (CMT), and macular volume at
      baseline; at 1, 3, and 6 months; and at final visit after primary IVB were
      retrospectively analyzed and compared between patients with and without SRD.
      RESULTS: SRD was found in 25 patients (34.2%). The baseline CMT was significantly
      thicker in patients with SRD than in those without it (648.4+/-200.5 MUm vs.
      440.3+/-119.6 MUm, P<0.001). Six months after primary IVB injection, a greater
      reduction in CMT change from baseline was observed in the SRD group (412.5+/
      227.2 MUm) than in the group without SRD (118.5+/-175.2 MUm) (P<0.001). The
      improvement of logarithm of the minimum angle of resolution VA was also greater
      in the SRD group than in the group without SRD (-0.64+/-0.52 and -0.28+/-0.62
      respectively, P=0.015). Logistic regression analysis showed that the presence of
      SRD was an independent factor for visual improvement in BRVO (P=0.027).
      CONCLUSION: Patients with SRD had greater functional and morphological
      improvements at 6 months after primary IVB therapy. The results of this study
      suggest that the presence of SRD observed on OCT may be an indicator of favorable
      clinical response after IVB injections and that in BRVO patients with SRD,
      bevacizumab may be a good alternative for treatment.

PMID- 23145864
TI  - Efficacy of probing with mitomycin-C in adults with primary acquired nasolacrimal
      duct obstruction.
AB  - PURPOSE: To evaluate the efficacy and safety of adjunctive mitomycin-c (MMC)
      during probing in adults with primary nasolacrimal duct (NLD) obstruction.
      METHODS: This is a prospective, comparative, randomized interventional study. A
      total of 40 adult patients with unilateral epiphora caused by primary NLD
      obstruction were treated and evaluated. Lacrimal probing and irrigation with
      adjunctive MMC (1 mL of 0.2 mg/mL, once) in cases and only probing in controls
      were done. At the end of 3 months, subjective improvement in epiphora and patency
      on syringing were evaluated. RESULTS: Complete subjective improvement in epiphora
      was found in 15% of cases as opposed to 0% in controls, at 3 months of follow-up.
      Moderate improvement was seen in 25% of cases as opposed to 5% of controls. Mild
      improvement was seen in 25% of cases as opposed to 35% in controls. The overall
      subjective improvement was seen in 65% of cases as opposed to 40% in controls. On
      syringing, NLD was patent in 30% of cases as opposed to 10% in controls at 3
      months of follow-up, which was not significant. CONCLUSIONS: Use of
      intraoperative MMC improves the success of probing to some extent. Being a
      minimally invasive procedure, it can be tried in patients who refuse or are not
      systemically fit for undergoing dacryocystorhinostomy.

PMID- 23145865
TI  - Nanoparticles in the treatment of angiogenesis-related blindness.
AB  - Nanoparticles can be used for the treatment of various retinal diseases. Due to
      small sizes, they can improve bioavailability of therapeutic agents and pass
      through biological barriers of the eye, such as the cornea, conjunctiva, sclera,
      and even more, blood-retinal barriers. Another important characteristic of
      nanoparticles is the ability to be fabricated based on the researchers' design
      through chemical processes. In this regard, they can act as a novel drug delivery
      system, enabling targeted therapies for angiogenesis-related blindness (ARB).
      With these possibilities, many researchers have utilized nanoparticles as novel
      therapeutic options for the treatment of exudative age-related macular
      degeneration and diabetic retinopathy, both of which are characterized by
      pathologic neovascularization. In this review, we summarize various attempts and
      rationales in using nanoparticles to treat ARB. After that, we discuss the
      toxicity of nanoparticles on the retina. We expect this review to be a stepping
      stone for novel therapeutics for ARB, resulting in improvement in visual
      outcomes.

PMID- 23145866
TI  - Impact of chemiluminescent enzyme immunoassay screening for human parvovirus B19
      antigen in Japanese blood donors.
AB  - BACKGROUND: To reduce the risk of human parvovirus B19 (B19V) transmission
      through contaminated blood for transfusion and plasma-derived products, the
      Japanese Red Cross (JRC) Blood Centers introduced B19V antigen screening by
      chemiluminescent enzyme immunoassay (CLEIA-B19V) in 2008. STUDY DESIGN AND
      METHODS: Donor samples that were positive by CLEIA-B19V screening were tested for
      B19V DNA. The sensitivity of CLEIA-B19V was tested using samples of all three
      genotypes and B19V DNA-positive donations. B19V DNA-positive donations and pooled
      plasma were quantitatively assayed for B19V DNA. B19V DNA-positive donations were
      phylogenetically analyzed by polymerase chain reaction direct sequencing.
      RESULTS: The sensitivity of CLEIA-B19V was inferred to be approximately 6.3 log
      IU/mL with the genotype samples and 6.4 log IU/mL with B19V DNA-positive donor
      samples. Of 417 CLEIA-B19V-positive samples from 1,035,560 donations in Hokkaido,
      Japan, 101 were positive for B19V DNA. The 198 strains of B19V DNA-positive
      donations in Hokkaido over the past 15 years clustered exclusively with Genotype
      1. After introduction of CLEIA-B19V, the viral load for B19V DNA in all 772
      pooled plasma for fractionation from donors in nationwide Japan did not exceed 4
      log IU/mL. CONCLUSION: CLEIA-B19V can detect all three genotypes of B19V (viral
      load >6.3 log IU/mL) and limit the viral load (<4 log IU/mL) in pooled plasma,
      and thus such screening has further reduced the risk of transfusion-transmitted
      B19V infection. These results show that CLEIA-B19V screening at the JRC Blood
      Centers can be an alternative approach to comply with recommendations regarding
      B19V in the United States and Europe.

PMID- 23145867
TI  - Theoretical study on the ring-opening of 1,3-disilacyclobutane and H2
      elimination.
AB  - The kinetics and thermochemistry of the decomposition pathways for 1,3
      disilacyclobutane (1,3-DSCB) in the gas phase were studied using the second-order
      Moller-Plesset (MP2) perturbation theory and coupled cluster methods with single,
      double, and perturbative triple excitations (CCSD(T)). The reactions examined
      include 2 + 2 cycloreversion to form two silenes by either a concerted or a
      stepwise mechanism, 1,1-, 1,2-, and 1,3-H(2) elimination, and the ring-opening
      initiated by 1,2-H shift to form an open-chain 1,3-disilabut-1-ylidene, which
      undergoes further decomposition to produce two pairs of silene/silylene species.
      The structures of the transition states for the concerted and the stepwise 2 + 2
      cycloreversion pathways are found to resemble closely those reported for the head
      to-tail and head-to-head dimerization, respectively. Comparison of the activation
      barriers demonstrates unambiguously that the stepwise cycloreversion
      (DeltaH(0)(?) = 66.1 kcal/mol) is favored over the concerted one (DeltaH(0)(?) =
      77.3 kcal/mol). A new pathway was established from the 1,4-diradical intermediate
      in the stepwise cycloreversion to form 1-silylmethylsilene via 1,3-H shift. The
      concerted 1,1-H(2) elimination is shown to have the lowest activation barrier of
      all H2 elimination reactions. Overall, the 1,2-H shift in 1,3-DSCB with concerted
      ring-opening to form 1,3-disilabut-1-ylidene is the most kinetically and
      thermodynamically favorable decomposition pathway, both at 0 and 298 K.

PMID- 23145868
TI  - Donkey pericardium as an alternative bioprosthetic heart valve material.
AB  - This study comparatively evaluates the characteristics of glutaraldehyde-treated
      acellular bovine and donkey pericardium using histological and electronic
      microscopic observation techniques, shrinkage temperature, and mechanical
      properties, as well as determining calcium and phosphorus content at 4 and 8
      weeks after the subcutaneous implantation of donkey and bovine pericardium in
      Wistar rats. Donkey pericardium was significantly thinner compared with bovine
      pericardium (1.622 +/-  0.161 mm vs. 4.027 +/- 0.401 mm, P < 0.0001) and was
      associated with significantly greater tensile strength (14.21 +/-  3.81 MPa vs.
      3.78 +/- 1.20 MPa, P = 0.001) and elastic modulus (81.67 +/- 20.41 MPa vs. 21.67
      +/- 11.69 MPa, P <  0.0001) over bovine pericardium. Shrinkage temperature of
      donkey pericardium was similar to that of bovine pericardium (87.43 +/- 0.55
      degrees C vs. 87.50 +/- 0.36 degrees C, P =  0.810). No differences between
      groups were observed for maximum load (donkey: 21.64 +/- 7.02 KN/m vs. bovine:
      15.05 +/- 4.50 KN/m, P = 0.082) and tear strength (donkey: 11.54 +/- 5.33 MPa vs.
      bovine: 10.69 +/-  3.77 MPa, P = 0.757). Calcium content was significantly lower
      in donkey pericardium compared with bovine pericardium at 4 weeks (690.15 +/-
      191.27 ug/g vs. 1381.73 +/- 62.52 ug/g, P = 0.001) and 8 weeks (205.24 +/- 62.40
      ug/g vs. 910.48 +/- 398.29 ug/g, P = 0.037). This preliminary study has confirmed
      that glutaraldehyde-tanned donkey pericardium, demonstrating reduced
      calcification and increased tensile strength, may provide a suitable
      bioprosthetic valve substitute.

PMID- 23145869
TI  - Clinical usefulness of (18) F-fluorodeoxyglucose positron emission
      tomography/computed tomography for patients with primary liver cancer with
      special reference to rare histological types, hepatocellular carcinoma with
      sarcomatous change and combined hepatocellular and cholangiocarcinoma.
AB  - AIM: The role of (18) F-fluorodeoxyglucose positron emission tomography (FDG-PET)
      in the diagnosis and staging of primary liver cancer has been demonstrated in
      several reports. However, no preoperative evaluations of sarcomatous
      hepatocellular carcinoma (HCC) and combined hepatocellular and cholangiocarcinoma
      (cHCC-CC) with FDG-PET have been reported so far. METHODS: Fifty-three HCC
      patients and three cHCC-CC patients who received liver resection or living-donor
      liver transplantation were enrolled in this study. All 56 patients had undergone
      preoperative FDG-PET, and a total of 67 HCC and three cHCC-CC were analyzed
      histologically. The relationship between clinicopathological features and the
      maximum standardized uptake value (SUVmax) of tumors were evaluated. RESULTS: The
      detection rate of HCC by FDG-PET was 43.3 %, and the sensitivity of FDG-PET for
      the detection of HCC was significantly associated with tumor differentiation,
      tumor size and microvascular invasion. All three cHCC-CC were detected by FDG
      PET. The SUVmax values of the three sarcomatous HCC (SUVmax 14.1, 18.6 and 25.0)
      and the three cHCC-CC (SUVmax 9.9, 12.0 and 13.0) were higher than that of the
      poorly differentiated HCC (mean SUVmax 5.7 +/- 2.3). CONCLUSION: SUVmax may be a
      useful diagnostic tool for the preoperative evaluation of the aggressiveness of
      primary liver cancers such as sarcomatous HCC and cHCC-CC.

PMID- 23145870
TI  - Sensing proteins through nanopores: fundamental to applications.
AB  - Proteins subjected to an electric field and forced to pass through a nanopore
      induce blockades of ionic current that depend on the protein and nanopore
      characteristics and interactions between them. Recent advances in the analysis of
      these blockades have highlighted a variety of phenomena that can be used to study
      protein translocation and protein folding, to probe single-molecule catalytic
      reactions in order to obtain kinetic and thermodynamic information, and to detect
      protein-antibody complexes, proteins with DNA and RNA aptamers, and protein-pore
      interactions. Nanopore design is now well controlled, allowing the development of
      future biotechnologies and medicine applications.

PMID- 23145872
TI  - A retrospective 3-to-5 year study of the reconstruction of oral function using
      implant-supported prostheses in patients with hypohidrotic ectodermal dysplasia.
AB  - Abstract   ABSTRACTThe aim of this study was to evaluate oral function
      rehabilitation in patients with hypohidrotic ectodermal dysplasia (HED) using
      implant-supported prostheses base on bone augmentation. From September 2005 and
      March 2009, twenty-five HED patients were chose to analyze clinical data in this
      study. The criteria for patient selection was including the patient displayed
      clinical features of HED, the number of congenitally missing teeth (>5), the age
      of patient (>16 years), the will of patient, and the tolerance of patient for
      bone graft surgery and implant placement. Follow-up evaluations was initiated
      from the time of prosthetic placement of implants and scheduled annually for 3-5
      years. The effects of oral function reconstruction were assessed based on the
      cumulative survival and success rates of implants, the health of the peri-implant
      area, and the degree of patient satisfaction. Twenty-five HED patients received
      169 conventional implants and 10 zygomatic implants (179 total implants). During
      3-5 years of post-loading evaluations, five of the 179 implants failed and three
      implants were removed. The 3-year success and cumulative survival rates were
      97.2% and 98.3%, respectively. Furthermore, periodontal probing and radiographic
      assessments showed that the 3-year incidence of peri-implantitis was 4.5%.
      Finally, HED patients expressed high degrees of satisfaction with their facial
      contours, comfort with the implant-supported prostheses, masticatory function,
      and pronunciation ability. The results of this 3-5 year retrospective study
      indicate that the oral function of HED patients can be effectively reconstructed
      using bone augmentation and implant-supported prostheses. However, longer-term
      results are warranted in the future.

PMID- 23145871
TI  - Exposure to a galactooligosaccharides/inulin prebiotic mix at different
      developmental time points differentially modulates immune responses in mice.
AB  - Prebiotics constitute emerging tools to alleviate immune pathologies. This study
      aimed to evaluate the effect of prebiotic exposure during perinatal and
      postweaning periods on immune and gut regulations. Mice were fed either a
      galactooligosaccharides/inulin prebiotic mix-enriched diet or a control diet
      during the perinatal and/or postweaning periods. Biomarkers related to gut
      barrier function (SCFA, heat shock proteins, zonula occludens protein-1, and
      mucin-2) and immune mechanisms (IgA, IgE, IgG1, IgG2a, IL-10, TGF-beta, IL-4, IL
      17A, and IFN-gamma) were analyzed. The milk of dams fed the prebiotic diet was
      more concentrated in both IgA and TGF-beta when prebiotics were introduced during
      both the perinatal and postweaning periods; IL-10, IgA, and IgG2a were increased
      in pups; and expression of intestinal markers was more pronounced. Postweaning
      exposure to prebiotics alone induced higher INF-gamma and TGF-beta levels,
      whereas IgA levels fell. Combined exposure periods (perinatal/postweaning) to
      prebiotics increased tolerance-related immunoglobulins in pups and reinforced gut
      barrier functions.

PMID- 23145873
TI  - Case control study to identify risk factors for acute hepatitis C virus infection
      in Egypt.
AB  - BACKGROUND: Identification of risk factors of acute hepatitis C virus (HCV)
      infection in Egypt is crucial to develop appropriate prevention strategies.
      METHODS: We conducted a case-control study, June 2007-September 2008, to
      investigate risk factors for acute HCV infection in Egypt among 86 patients and
      287 age and gender matched controls identified in two infectious disease
      hospitals in Cairo and Alexandria. Case-patients were defined as: any patient
      with symptoms of acute hepatitis; lab tested positive for HCV antibodies and
      negative for HBsAg, HBc IgM, HAV IgM; and 7-fold increase in the upper limit of
      transaminase levels. Controls were selected from patients' visitors with negative
      viral hepatitis markers. Subjects were interviewed about previous exposures
      within six months, including community-acquired and health-care associated
      practices. RESULTS: Case-patients were more likely than controls to have received
      injection with a reused syringe (OR=23.1, CI 4.7-153), to have been in prison
      (OR=21.5, CI 2.5-479.6), to have received IV fluids in a hospital (OR=13.8, CI
      5.3-37.2), to have been an IV drug user (OR=12.1, CI 4.6-33.1), to have had
      minimal surgical procedures (OR=9.7, CI 4.2-22.4), to have received IV fluid as
      an outpatient (OR=8, CI 4-16.2), or to have been admitted to hospital (OR=7.9, CI
      4.2-15) within the last 6 months. Multivariate analysis indicated that unsafe
      health facility practices are the main risk factors associated with transmission
      of HCV infection in Egypt. CONCLUSION: In Egypt, focusing acute HCV prevention
      measures on health-care settings would have a beneficial impact.

PMID- 23145874
TI  - A study of diverse clinical decision support rule authoring environments and
      requirements for integration.
AB  - BACKGROUND: Efficient rule authoring tools are critical to allow clinical
      Knowledge Engineers (KEs), Software Engineers (SEs), and Subject Matter Experts
      (SMEs) to convert medical knowledge into machine executable clinical decision
      support rules. The goal of this analysis was to identify the critical success
      factors and challenges of a fully functioning Rule Authoring Environment (RAE) in
      order to define requirements for a scalable, comprehensive tool to manage
      enterprise level rules. METHODS: The authors evaluated RAEs in active use across
      Partners Healthcare, including enterprise wide, ambulatory only, and system
      specific tools, with a focus on rule editors for reminder and medication rules.
      We conducted meetings with users of these RAEs to discuss their general
      experience and perceived advantages and limitations of these tools. RESULTS:
      While the overall rule authoring process is similar across the 10 separate RAEs,
      the system capabilities and architecture vary widely. Most current RAEs limit the
      ability of the clinical decision support (CDS) interventions to be standardized,
      sharable, interoperable, and extensible. No existing system meets all
      requirements defined by knowledge management users. CONCLUSIONS: A successful,
      scalable, integrated rule authoring environment will need to support a number of
      key requirements and functions in the areas of knowledge representation,
      metadata, terminology, authoring collaboration, user interface, integration with
      electronic health record (EHR) systems, testing, and reporting.

PMID- 23145875
TI  - Voltage-driven Ca(2+) binding at the L-type Ca(2+) channel triggers cardiac
      excitation-contraction coupling prior to Ca(2+) influx.
AB  - The activation of the ryanodine Ca(2+) release channels (RyR2) by the entry of
      Ca(2+) through the L-type Ca(2+) channels (Cav1.2) is believed to be the primary
      mechanism of excitation-contraction (EC) coupling in cardiac cells. This proposed
      mechanism of Ca(2+)-induced Ca(2+) release (CICR) cannot fully account for the
      lack of a termination signal for this positive feedback process. Using Cav1.2
      channel mutants, we demonstrate that the Ca(2+)-impermeable
      alpha(1)1.2/L775P/T1066Y mutant introduced through lentiviral infection into
      neonate cardiomyocytes triggers Ca(2+) transients in a manner independent of
      Ca(2+) influx. In contrast, the alpha(1)1.2/L775P/T1066Y/4A mutant, in which the
      Ca(2+)-binding site of the channel was destroyed, supports neither the
      spontaneous nor the electrically evoked contractions. Ca(2+) bound at the channel
      selectivity filter appears to initiate a signal that is conveyed directly from
      the channel pore to RyR2, triggering contraction of cardiomyocytes prior to
      Ca(2+) influx. Thus, RyR2 is activated in response to a conformational change in
      the L-type channel during membrane depolarization and not through interaction
      with Ca(2+) ions diffusing in the junctional gap space. Accordingly, termination
      of the RyR2 activity is achieved when the signal stops upon the return of the L
      channel to the resting state. We propose a new model in which the physical link
      between Cav1.2 and RyR2 allows propagation of a conformational change induced at
      the open pore of the channel to directly activate RyR2. These results highlight
      Cav1.2 as a signaling protein and provide a mechanism for terminating the release
      of Ca(2+) from RyR2 through protein-protein interactions. In this model, the L
      type channel is a master regulator of both initiation and termination of EC
      coupling in neonate cardiomyocytes.

PMID- 23145876
TI  - Systematic assessment of the representativeness of published collections of the
      traditional literature on Chinese medicine.
AB  - BACKGROUND: The traditional Chinese medical literature provides a substantial
      resource for natural products research. When undertaking systematic searches,
      investigators need to assess the scope, content, and relevance of collections
      both singly and in comparison. OBJECTIVES: This study examines eight collections
      of pre-modern literature, develops an approach to quantitatively assess their
      content, and compares their relative inclusivity. METHODS: All publications
      listed in each collection were collated and a uniform scoring system was
      developed to account for variant editions, incorporation of multiple books under
      a single title, addition of commentaries, and other factors affecting content.
      Comparisons were undertaken between collections to determine the degree of
      overlap, genres of literature represented, and relevance to natural products
      research. RESULTS: Following adjustments for differences in how books were
      listed, duplications, and variant editions, Zhong Hua Yi Dian (Encyclopaedia of
      Traditional Chinese Medicine) (4th edition CD) is the largest collection of
      complete books containing 1009 different books. Zhong Guo Ben Cao Quan Shu (The
      Complete Collection of Traditional Texts on Chinese Materia Medica) contains 2026
      titles including multiple editions and extracts, so after adjustments the number
      of different complete books is approximately 740. No collection was fully
      inclusive of the others, but Zhong Hua Yi Dian includes between 52.1% and 91.5%
      of the books in the six smaller collections. CONCLUSIONS: Comparing traditional
      collections is complex due to variant editions and multiple titles. This
      necessitates examination of the text rather than title alone. Prior to
      undertaking systematic searches, the characteristics of collections need to be
      investigated, duplicated books identified, and differences between editions
      should be assessed. Its size, electronic format, and broad spread of genres makes
      Zhong Hua Yi Dian suitable for systematic searches, but due to the lack of
      bibliographical detail on included books, cross-referencing to other collections
      is recommended.

PMID- 23145878
TI  - A switchable ferrocene-based [1]rotaxane with an electrochemical signal output.
AB  - A [1]rotaxane, in which a linear rod is attached to one cyclopentadienyl (Cp)
      ring of a ferrocene unit and threaded into a dibenzo-24-crown-8 connected to the
      other Cp ring, was prepared. The mechanical motion of the rod-like part relative
      to the macrocycle has been demonstrated using (1)H NMR spectroscopy. Cyclic
      voltammetry (CV) showed that the system can be chemically switched between
      electrochemically reversible and irreversible states, depending on the inclusion
      and exclusion of the ammonium/amine group from the macrocycle.

PMID- 23145877
TI  - The shell-forming proteome of Lottia gigantea reveals both deep conservations and
      lineage-specific novelties.
AB  - Proteins that are occluded within the molluscan shell, the so-called shell matrix
      proteins (SMPs), are an assemblage of biomolecules attractive to study for
      several reasons. They increase the fracture resistance of the shell by several
      orders of magnitude, determine the polymorph of CaCO(3) deposited, and regulate
      crystal nucleation, growth initiation and termination. In addition, they are
      thought to control the shell microstructures. Understanding how these proteins
      have evolved is also likely to provide deep insight into events that supported
      the diversification and expansion of metazoan life during the Cambrian radiation
      543 million years ago. Here, we present an analysis of SMPs isolated form the
      CaCO(3) shell of the limpet Lottia gigantea, a gastropod that constructs an
      aragonitic cross-lamellar shell. We identified 39 SMPs by combining proteomic
      analysis with genomic and transcriptomic database interrogations. Among these
      proteins are various low-complexity domain-containing proteins, enzymes such as
      peroxidases, carbonic anhydrases and chitinases, acidic calcium-binding proteins
      and protease inhibitors. This list is likely to contain the most abundant SMPs of
      the shell matrix. It reveals the presence of both highly conserved and lineage
      specific biomineralizing proteins. This mosaic evolutionary pattern suggests that
      there may be an ancestral molluscan SMP set upon which different conchiferan
      lineages have elaborated to produce the diversity of shell microstructures we
      observe nowadays.

PMID- 23145879
TI  - Equine myeloperoxidase: a novel biomarker in synovial fluid for the diagnosis of
      infection.
AB  - REASONS FOR PERFORMING STUDY: Equine joint infection is a life-threatening
      disorder, and confirmation of the diagnosis can be difficult. Synovial fluid
      biomarkers may assist the discrimination between infectious and noninfectious
      joint disease. OBJECTIVES: This study investigates whether the immunological
      detection of total and enzymatically active myeloperoxidase (MPO) assists the
      diagnosis of joint infection in horses. METHODS: The following 4 sample groups
      were included: healthy; osteochondritis dissecans (OCD); traumatic synovitis; and
      culture-confirmed infected joints. Synovial fluid was analysed for total MPO by a
      horse-specific sandwich enzyme-linked immunosorbent assay (ELISA) and for active
      MPO using the specific immunological extraction followed by enzymatic detection
      (SIEFED) technique. Western blot analysis was performed to confirm the antibody
      specificity. RESULTS: Synovial fluid from infected joints contained significantly
      more total and active MPO than samples from healthy joints, joints affected by
      OCD and joints with traumatic synovitis. Cut-off values were set at 5000 and 350
      ng/ml for total and active MPO, respectively, with fair sensitivity, specificity,
      positive and negative predictive values and likelihood ratios for infection.
      Correlation coefficients were reported between the total as well as the active
      MPO levels and the routine synovial fluid parameters, i.e. the white blood cell
      count, the neutrophil count and the total protein level. No correlation was
      observed between MPO and either the age of the horse or the joint affected.
      Western blotting confirmed the antibody specificity for equine MPO. CONCLUSIONS
      AND POTENTIAL RELEVANCE: Synovial fluid MPO was identified as a very promising
      biomarker to augment the discrimination of infectious vs. noninfectious joint
      disease in horses. Both ELISA and SIEFED techniques can be used for its specific
      and rapid detection. The analysis of synovial fluid MPO can be used as a
      complementary test to aid in the discrimination between infectious and
      noninfectious joint disease, especially when the white blood cell counts and the
      total protein level are inconclusive.

PMID- 23145880
TI  - Review: efficacy of alginate supplementation in relation to appetite regulation
      and metabolic risk factors: evidence from animal and human studies.
AB  - This review provides a critical update on human and animal studies investigating
      the effect of alginate supplementation on appetite regulation, glycaemic and
      insulinemic responses, and lipid metabolism with discussion of the evidence on
      potential mechanisms, efficacy and tolerability. Dependent on vehicle applied for
      alginate supplementation, the majority of animal and human studies suggest that
      alginate consumption does suppress satiety and to some extent energy intake. Only
      one long-term intervention trial found effects on weight loss. In addition,
      alginates seem to exhibit beneficial influence on postprandial glucose absorption
      and insulin response in animals and humans. However, alginate supplementation was
      only found to have cholesterol-lowering properties in animals. Several mechanisms
      have been suggested for the positive effect observed, which involve delayed
      gastric emptying, increased viscosity of digesta and slowed nutrient absorption
      in the small intestine upon alginate gel formation. Despite reasonable efficacy
      and tolerability from the acute or short-term studies, we still realize there is
      a critical need for development of optimal alginate types and vehicles as well as
      studies on further long-term investigation on alginate supplementation in humans
      before inferring that it could be useful in the management of obesity and the
      metabolic syndrome.

PMID- 23145881
TI  - Improvements in sleep quality and gait speed after cataract surgery.
AB  - BACKGROUND: Gait speed and sleep quality are health indices related to longevity
      and mortality. In the present study, we measured sleep quality, quality of life,
      gait speed, and visual acuity before and after cataract surgery to evaluate the
      efficacy of the procedure on systemic health. METHODS: The study was conducted on
      155 patients (93 women; average age 74.8 years) undergoing cataract surgery with
      the implantation of a yellow soft acrylic lens. Patients were evaluated using the
      Pittsburgh Sleep Quality Index (PSQI) and the National Eye Institute Visual
      Function Questionnaire 25 (VFQ-25; vision-related quality of life) before and
      then 2 and 7 months after surgery. Four-meter gait speed was also determined.
      RESULTS: Of the 155 patients, 68 (43.9%) were classified as poor sleepers
      (PSQI>5.5) prior to surgery. Significant improvements were noted in sleep 2
      months after surgery (p<0.05, paired t-test), but thereafter the improvements
      were not significant. Prior to surgery, 117 patients (77.0%) were classified as
      slow walkers (speed<1.0 meter/s). Gait speed increased significantly in these
      patients 2 months after surgery (p<0.001, paired t-test). Multiple regression
      analysis revealed significant correlations between the preoperative VFQ-25 score
      and both PSQI (p<0.05) and gait speed (p<0.001). Postoperative increases in the
      VFQ-25 score were positively correlated with decreases in the PSQI (p<0.05).
      Improvements in visual acuity were correlated with improvements in the VFQ-25
      score, but not with either PSQI or gait speed. CONCLUSION: Cataract surgery
      effectively improves sleep quality and slow gait speed.

PMID- 23145882
TI  - Zinc leaching from tire crumb rubber.
AB  - Because tires contain approximately 1-2% zinc by weight, zinc leaching is an
      environmental concern associated with civil engineering applications of tire
      crumb rubber. An assessment of zinc leaching data from 14 studies in the
      published literature indicates that increasing zinc leaching is associated with
      lower pH and longer leaching times, but the data display a wide range of zinc
      concentrations, and do not address the effect of crumb rubber size or the
      dynamics of zinc leaching during flow through porous crumb rubber. The present
      study was undertaken to investigate the effect of crumb rubber size using the
      synthetic precipitation leaching procedure (SPLP), the effect of exposure time
      using quiescent batch leaching tests, and the dynamics of zinc leaching using
      column tests. Results indicate that zinc leaching from tire crumb rubber
      increases with smaller crumb rubber and longer exposure time. Results from SPLP
      and quiescent batch leaching tests are interpreted with a single-parameter
      leaching model that predicts a constant rate of zinc leaching up to 96 h.
      Breakthrough curves from column tests displayed an initial pulse of elevated zinc
      concentration (~3 mg/L) before settling down to a steady-state value (~0.2 mg/L),
      and were modeled with the software package HYDRUS-1D. Washing crumb rubber
      reduces this initial pulse but does not change the steady-state value. No
      leaching experiment significantly reduced the reservoir of zinc in the crumb
      rubber.

PMID- 23145884
TI  - Antibacterial butenolides from the Korean tunicate Pseudodistoma antinboja.
AB  - Six new (1, 2, and 5-8) and three known (3, 4, and 9) butenolide metabolites were
      isolated from the tunicate Pseudodistoma antinboja by activity-guided
      fractionations. The structures were elucidated by combined NMR and MS
      spectroscopic methods. These compounds were evaluated for their antibacterial
      activity, and most of them exhibited moderate to significant activity that
      selectively targeted Gram-positive strains and did not exhibit cytotoxicity in
      the MTT assay at 100 MUM. Cadiolides 5-9 in particular exhibited significant
      antibacterial activity that was comparable to or even better than those of
      marketed drugs such as vancomycin and linezolid against all of the drug-resistant
      strains tested.

PMID- 23145885
TI  - Comparison of manual versus automatic continuous positive airway pressure
      titration and the development of a predictive equation for therapeutic continuous
      positive airway pressure in Chinese patients with obstructive sleep apnoea.
AB  - BACKGROUND AND OBJECTIVE: Whether the therapeutic nasal continuous positive
      airway pressure (CPAP) derived from manual titration is the same as derived from
      automatic titration is controversial. The purpose of this study was to compare
      the therapeutic pressure derived from manual titration with automatic titration.
      METHODS: Fifty-one patients with obstructive sleep apnoea (OSA) (mean
      apnoea/hypopnoea index (AHI) = 50.6 +/- 18.6 events/h) who were newly diagnosed
      after an overnight full polysomnography and who were willing to accept CPAP as a
      long-term treatment were recruited for the study. Manual titration during full
      polysomnography monitoring and unattended automatic titration with an automatic
      CPAP device (REMstar Auto) were performed. A separate cohort study of one hundred
      patients with OSA (AHI = 54.3 +/- 18.9 events/h) was also performed by observing
      the efficacy of CPAP derived from manual titration. RESULTS: The treatment
      pressure derived from automatic titration (9.8 +/- 2.2 cmH(2)O) was significantly
      higher than that derived from manual titration (7.3 +/- 1.5 cmH(2)O; P < 0.001)
      in 51 patients. The cohort study of 100 patients showed that AHI was
      satisfactorily decreased after CPAP treatment using a pressure derived from
      manual titration (54.3 +/- 18.9 events/h before treatment and 3.3 +/- 1.7
      events/h after treatment; P < 0.001). CONCLUSIONS: The results suggest that
      automatic titration pressure derived from REMstar Auto is usually higher than the
      pressure derived from manual titration.

PMID- 23145886
TI  - Anomalous diffusion kinetics of the precursor film that spreads from polymer
      droplets.
AB  - The radii R of the area wetted by precursor films spreading from small droplets
      of polymer liquids are found to vary as R ~ t(nu) with nu = 0.31-0.42, in
      contradiction to the 0.5 exponent indicated in previous studies. The experiments
      reported here are for three of the same polymer liquids used in the previous
      studies-methyl-terminated polydimethylsiloxane (PDMS), tetrakis(2
      ethylhexoxy)silane, and squalane-and a linear chain perfluoropolyether polymer.
      When the droplets dissipate into pancake-shaped films, the spreading kinetics
      slows down to a variety of different diffusion processes for the different
      molecules, as they are no longer forced to move en masse across the surface by
      molecules being fed into the center of the film by the droplet.

PMID- 23145887
TI  - Ion permeation by a folded multiblock amphiphilic oligomer achieved by
      hierarchical construction of self-assembled nanopores.
AB  - A multiblock amphiphilic molecule 1, with a tetrameric alternating sequence of
      hydrophilic and hydrophobic units, adopts a folded structure in a liposomal
      membrane like a multipass transmembrane protein, and is able to transport alkali
      metal cations through the membrane. Hill's analysis and conductance measurements,
      analyzed by the Hille equation, revealed that the tetrameric assembly of 1 forms
      a 0.53 nm channel allowing for permeation of cations. Since neither 3, bearing
      flexible hydrophobic units and forming no stacked structures in the membrane, nor
      2, a monomeric version of 1, is able to transport cations, the folded
      conformation of 1 in the membrane is likely essential for realizing its function.
      Thus, function and hierarchically formed higher-order structures of 1, is
      strongly correlated with each other like proteins and other biological
      macromolecules.

PMID- 23145888
TI  - Diet and phylogeny shape the gut microbiota of Antarctic seals: a comparison of
      wild and captive animals.
AB  - The gut microbiota of mammals underpins the metabolic capacity and health of the
      host. Our understanding of what influences the composition of this community has
      been limited primarily to evidence from captive and terrestrial mammals.
      Therefore, the gut microbiota of southern elephant seals, Mirounga leonina, and
      leopard seals, Hydrurga leptonyx, inhabiting Antarctica were compared with
      captive leopard seals. Each seal exhibited a gut microbiota dominated by four
      phyla: Firmicutes (41.5 +/- 4.0%), Fusobacteria (25.6 +/- 3.9%), Proteobacteria
      (17.0 +/- 3.2%) and Bacteroidetes (14.1 +/- 1.7%). Species, age, sex and
      captivity were strong drivers of the composition of the gut microbiota, which can
      be attributed to differences in diet, gut length and physiology and social
      interactions. Differences in particular prey items consumed by seal species could
      contribute to the observed differences in the gut microbiota. The longer gut of
      the southern elephant seal provides a habitat reduced in available oxygen and
      more suitable to members of the phyla Bacteroidetes compared with other hosts.
      Among wild seals, 16 'core' bacterial community members were present in the gut
      of at least 50% of individuals. As identified between southern elephant seal
      mother-pup pairs, 'core' members are passed on via vertical transmission from a
      young age and persist through to adulthood. Our study suggests that these hosts
      have co-evolved with their gut microbiota and core members may provide some
      benefit to the host, such as developing the immune system. Further evidence of
      their strong evolutionary history is provided with the presence of 18 shared
      'core' members in the gut microbiota of related seals living in the Arctic. The
      influence of diet and other factors, particularly in captivity, influences the
      composition of the community considerably. This study suggests that the gut
      microbiota has co-evolved with wild mammals as is evident in the shared presence
      of 'core' members.

PMID- 23145889
TI  - Inconsistencies between medical records and patient-reported recommendations for
      follow-up after abnormal Pap tests.
AB  - PURPOSE: Adherence with recommended follow-up after an abnormal Pap test is a
      critical step in the prevention of cervical cancer. Here, we focused on
      identifying inconsistencies between self-reported and health department record
      recommendations for follow-up. METHODS: Self-reported recommendations for follow
      up were collected by questionnaire from 519 women with abnormal Pap tests in
      rural Appalachia as part of a trial of the efficacy of patient navigation. Health
      department medical records were reviewed to collect healthcare provider
      recommendations. Measures of inconsistency (discordance) were calculated for
      overall recommendations and each of three particular follow-up recommendations:
      repeat Pap test, referral for further tests, and other gynecologist referral.
      RESULTS: The inconsistencies between the recommendation from the health
      department records and self-reports ranged from 15.0% (repeat Pap test) to 35.3%
      (gynecologist referral). Inconsistencies were most common among women with a
      history of abnormal Pap tests and those with more severe initial results.
      Recommendations for repeat Pap tests were correctly reported most often when the
      women recalled receiving a letter stating the results. Of greatest concern were
      the inconsistencies regarding recommendations for referral to a gynecologist. The
      more severe the Pap test result, the greater the odds of inaccurate self-reports
      of receiving a referral to a gynecologist for follow-up, p<0.001. CONCLUSIONS:
      Clinicians should be aware that patients with a history of abnormal results and
      severe Pap test abnormalities are at risk of misreporting recommendations for
      follow up.

PMID- 23145890
TI  - The "Welcome to Medicare" visit: a missed opportunity for cancer screening among
      women?
AB  - BACKGROUND: On January 1, 2005, Medicare began covering a "Welcome to Medicare"
      visit (WMV) for new enrollees with fee-for-service (FFS) Medicare (Parts A and
      B). The new benefit was expected to increase demand for mammography and Pap tests
      among women transitioning onto Medicare. This study examined whether Medicare's
      coverage of a WMV influenced the use of mammography and Pap tests among women
      aged 65 and 66 years with FFS Medicare. METHODS: Medicare Current Beneficiary
      Survey (MCBS) data from 2001 to 2007 were linked with Medicare claims.
      Utilization rates for preventive visits, mammography, and Pap tests were measured
      among women entering Medicare. Multivariate logistic regressions were estimated
      to quantify the effects of the new Medicare benefit on the use of these screening
      tests, controlling for patient characteristics. RESULTS: Regression-adjusted
      mammography and Pap test rates did not increase after WMV coverage was
      introduced. The 2005 reform had nonsignificant trivial effects on the use of both
      tests, most likely because few of the women who were eligible for a WMV took
      advantage of it. CONCLUSIONS: Medicare coverage of a WMV had no impact on
      mammography screenings or Pap tests among women who were eligible for the
      benefit.

PMID- 23145891
TI  - MTHFR C677T polymorphism modifies the effect of HRT on metabolic parameters in
      postmenopausal women.
AB  - OBJECTIVE: To assess the interaction of the MTHFR C677T polymorphism with changes
      in lipid and glucose metabolism effected by oral hormone replacement therapy
      (HRT) in postmenopausal women. METHODS: In this open-label, prospective,
      interventional study, parameters of lipid and glucose metabolism, as well as
      homocysteine, were assessed in 97 postmenopausal women at baseline and 1 year
      after the initiation of HRT. Participants were stratified into three subgroups,
      according to the MTHFR C677T polymorphism (wild-type: CC genotype; heterozygous:
      CT genotype; homozygous for the mutant variable: TT genotype). RESULTS: The TT
      genotype was associated with an elevation of total and low density lipoprotein
      (LDL) cholesterol, while CT and CC genotypes were associated with a reduction of
      total cholesterol and LDL cholesterol after 1 year of HRT (p = 0.032 for total
      cholesterol and p = 0.002 for LDL cholesterol). Women with the TT genotype had
      higher glucose levels in contrast to women with the CC genotype who had lower
      glucose levels after 1 year of HRT (p = 0.011). Additionally, CC carriers under
      HRT had a significant elevation of apolipoprotein A1 levels (p = 0.018),
      contrarily to CT and TT genotypes. CONCLUSION: While HRT was associated with
      favorable changes in lipid and metabolic parameters in carriers of the CC
      genotype, this effect was not evident in carriers of the T allele. The MTHFR
      C677T polymorphism may modify the effect of HRT on lipid and metabolic parameters
      in postmenopausal women.

PMID- 23145892
TI  - Ab initio study of the lowest-lying electronic states of LuCl molecules.
AB  - By using the CASSCF/MRCI methods, the theoretical electronic structure of the
      LuCl molecule has been investigated. These methods have been performed for 20
      singlet and triplet electronic states in the representation (2s+1)Lambda((+/-)).
      Calculated potential energy curves (PECs) are also displayed. Spectroscopic
      constants including the harmonic vibrational wavenumber omega(e) (cm(-1)), the
      relative electronic energy T(e) (cm(-1)) referred to the ground state, and the
      equilibrium internuclear distance R(e) (A) have been predicted for all of the
      singlet and triplet electronic states situated below 43,000 cm(-1). Spin-orbit
      effects have also been taken into consideration and calculated for the lowest
      lying electronic states in the representation Omega((+/-)).

PMID- 23145893
TI  - Reply to: asystole to cross-clamp period predicts development of biliary
      complications in liver transplantation using donation after cardiac death donors.

PMID- 23145894
TI  - Impact of pulsatile perfusion on clinical outcomes of neonates and infants with
      complex pathologies undergoing cardiopulmonary bypass procedures.
AB  - The aim of this clinical trial was to evaluate the pulsatile perfusion mode in
      pediatric patients who had complex cardiac pathologies according to Jenkins
      stratifications (category 4) undergoing cardiopulmonary bypass procedures (CPB).
      Patients with transposition of great arteries (TGA) and ventricular septal defect
      (VSD) were included in this clinical study. Eighty-nine consecutive pediatric
      patients undergoing open heart surgery for repair of TGA-VSD were prospectively
      entered into the study and were randomly assigned to either the pulsatile
      perfusion group (Group P, n = 58) or the nonpulsatile perfusion group (Group NP,
      n = 31). There were no differences between groups in terms of demographical and
      intraoperative parameters. The pulsatile group needed significantly less
      inotropic support (P < 0.05) and had lower lactate levels (P < 0.001), higher
      urine output (P < 0.01), and higher albumin levels (P < 0.05). In addition, the
      pulsatile group had less ICU (P < 0.01) and hospital stays (P < 0.001). We
      conclude that the use of pulsatile flow is a better option and should be
      considered for repair of the complex congenital heart defects.

PMID- 23145897
TI  - MAXILLARY SINUS AUGMENTATION AND IMPLANT PLACEMENT USING VENOUS BLOOD WITHOUT
      GRAFT MATERIAL: A CASE LETTER.
AB  - Abstract   AbstractObjective: Restoration of lost dentition in the severely
      atrophic posterior maxilla has been successfully treated with various sinus
      augmentation techniques such as using bone grafts and bone substitutes are
      frequently used to enable placement of dental implants. The aim of this study was
      to evaluate whether sinus membrane elevation and the simultaneous insertion of
      titanium implants without additional grafting material constitute a valid
      technique for bone augmentation of the maxillary sinus floor.Material and
      methods: A 35-year-old female patient evaluated with lost dentition in the left
      posterior maxilla. Preoperative cone beam computerized tomography (CBCT) were
      taken to guide the surgery. The sinus lift was performed and two implants were
      placed simultaneously in the residual subantral bone. The collected peripheral
      venous blood was applied to support the sinus membrane over the implant apex.
      Computed tomography (CT) was performed after 6 months healing period.Results:
      Comparisons of pre- and postoperative CT radiography clearly demonstrated new
      bone formation and new sinus floors were found within the compartment created by
      the sinus membrane elevation procedure. All implants remained stable during the
      healing period in clinical evaluations therefore definitive fixed prosthesis
      inserted. Conclusion: The case report showed that sinus membrane elevation
      without the use of bone graft material was found to be a predictable technique
      for bone augmentation of the maxillary sinus floor.

PMID- 23145895
TI  - Selective testing for Trypanosoma cruzi: the first year after implementation at
      Canadian Blood Services.
AB  - BACKGROUND: Various testing strategies may reduce the risk of Chagas disease
      transmission in nonendemic, low-prevalence countries. Results of the first year
      of selective testing of at-risk donors at Canadian Blood Services are reported.
      STUDY DESIGN AND METHODS: Since February 2009, platelets were not produced from
      at-risk donors. Since May 2010, at-risk donors were tested for Trypanosoma cruzi
      antibodies. Donors testing positive were interviewed about risk factors, and
      lookback studies were initiated. RESULTS: There were 7255 at-risk donors of
      421,979 donors screened (1.72%). Risk factors were born in Latin America (50.6%),
      mother or maternal grandmother born in Latin America (28%), and 6 months or more
      travel history or residence in Latin America (19%). Sixteen (16) at-risk donors
      had T. cruzi repeat-reactive test results of whom 13 confirmed positive. Eleven
      of 13 were born in Latin America (nine in Paraguay and two in Argentina), and the
      other two were born in Canada but had short-term travel history and mothers who
      had been born in Latin America. Ten of the donors spoke German as their first
      language (all of those born in Paraguay and one born in Canada). There were 148
      previous donations (176 components transfused) evaluated by lookback, of which
      28% of recipients could be tested. None were positive. CONCLUSION: Selective
      testing has mitigated a small risk to the blood supply with very few false
      positive results. Most positive donors were born in a risk country, with a
      concentration of German-speaking immigrants from Paraguay. Residency or travel
      alone were not clear risk factors.

PMID- 23145898
TI  - Bixin activates PPARalpha and improves obesity-induced abnormalities of
      carbohydrate and lipid metabolism in mice.
AB  - Peroxisome proliferator-activated receptor alpha (PPARalpha) is a ligand
      activated transcription factor that regulates the expression of the genes
      involved in fatty acid oxidation. PPARalpha activators induce fatty acid
      oxidation in the liver, thereby improving lipid and carbohydrate metabolism in
      obese mice. In this study, the dietary cis-carotenoids bixin and norbixin, which
      are commonly used in the food coloring industry, were found to activate PPARalpha
      by luciferase reporter assays using GAL4/PPARalpha chimeric and full-length
      PPARalpha systems. Treatment with bixin and norbixin induced the mRNA expression
      of PPARalpha target genes involved in fatty acid oxidation in PPARalpha
      expressing HepG2 hepatocytes. In obese KK-Ay mice, bixin treatment suppressed the
      development of hyperlipidemia and hepatic lipid accumulation. In the livers of
      bixin-treated mice, the mRNA levels of PPARalpha target genes related to fatty
      acid oxidation were up-regulated. Moreover, bixin treatment also improved obesity
      induced dysfunctions of carbohydrate metabolism, such as hyperglycemia,
      hyperinsulinemia, and hypoadiponectinemia. Glucose tolerance test and insulin
      tolerance test revealed that glucose intolerance and insulin resistance in KK-Ay
      obese mice were attenuated by the treatment with bixin. These results indicate
      that bixin acts as a food-derived agonist of PPARalpha, and bixin treatment is
      useful for the management of obesity-induced metabolic dysfunctions in mice.

PMID- 23145900
TI  - No prognostic impact of P2RY8-CRLF2 fusion in intermediate cytogenetic risk
      childhood B-cell acute lymphoblastic leukaemia.

PMID- 23145899
TI  - Repeated Aspergillus isolation in respiratory samples from non-immunocompromised
      patients not selected based on clinical diagnoses: colonisation or infection?
AB  - BACKGROUND: Isolation of Aspergillus from lower respiratory samples is associated
      with colonisation in high percentage of cases, making it of unclear significance.
      This study explored factors associated with diagnosis (infection vs.
      colonisation), treatment (administration or not of antifungals) and prognosis
      (mortality) in non-transplant/non-neutropenic patients showing repeated isolation
      of Aspergillus from lower respiratory samples. METHODS: Records of adult patients
      (29 Spanish hospitals) presenting >= 2 respiratory cultures yielding Aspergillus
      were retrospectively reviewed and categorised as proven (histopathological
      confirmation) or probable aspergillosis (new respiratory signs/symptoms with
      suggestive chest imaging) or colonisation (symptoms not attributable to
      Aspergillus without dyspnoea exacerbation, bronchospasm or new infiltrates).
      Logistic regression models (step-wise) were performed using Aspergillosis
      (probable + proven), antifungal treatment and mortality as dependent variables.
      Significant (p < 0.001) models showing the highest R2 were considered. RESULTS: A
      total of 245 patients were identified, 139 (56.7%) with Aspergillosis.
      Aspergillosis was associated (R2 = 0.291) with ICU admission (OR = 2.82),
      congestive heart failure (OR = 2.39) and steroids pre-admission (OR = 2.19) as
      well as with cavitations in X-ray/CT scan (OR = 10.68), radiological worsening
      (OR = 5.22) and COPD exacerbations/need for O2 interaction (OR = 3.52).
      Antifungals were administered to 79.1% patients with Aspergillosis (100% proven,
      76.8% probable) and 29.2% colonised, with 69.5% patients receiving voriconazole
      alone or in combination. In colonised patients, administration of antifungals was
      associated with ICU admission at hospitalisation (OR = 12.38). In Aspergillosis
      patients its administration was positively associated (R(2) = 0.312) with
      bronchospasm (OR = 9.21) and days in ICU (OR = 1.82) and negatively with Gold III
      + IV (OR = 0.26), stroke (OR = 0.024) and quinolone treatment (OR = 0.29).
      Mortality was 78.6% in proven, 41.6% in probable and 12.3% in colonised patients,
      and was positively associated in Aspergillosis patients (R2 = 0.290) with
      radiological worsening (OR = 3.04), APACHE-II (OR = 1.09) and number of
      antibiotics for treatment (OR = 1.51) and negatively with species other than A.
      fumigatus (OR = 0.14) and aspergillar tracheobronchitis (OR = 0.27). CONCLUSIONS:
      Administration of antifungals was not always closely linked to the diagnostic
      categorisation (colonisation vs. Aspergillosis), being negatively associated with
      severe COPD (GOLD III + IV) and concomitant treatment with quinolones in patients
      with Aspergillosis, probably due to the similarity of signs/symptoms between this
      entity and pulmonary bacterial infections.

PMID- 23145901
TI  - Australian nurses in general practice, enabling the provision of cervical
      screening and well women's health care services: a qualitative study.
AB  - BACKGROUND: The role of Australian general practice nurses (PNs) has developed
      exponentially since the introduction of service based funding in 2005. In
      particular, their role has expanded to include cervical screening and well
      women's health care services provided under the supervision of a general
      practitioner (GP). While previous research identifies barriers to the provision
      of these services, this study sought to investigate enablers for nurse led care
      in this area. METHODS: A number of grounded theory methods including constantly
      comparing data, concurrent data collection and analysis and theoretical sampling
      are utilised in this qualitative, exploratory study. A purposive sample of PNs
      who completed the required program of education in order to provide cervical
      screening and well women's health care services was recruited to the study. Data
      is presented in categories, however a limitation of the study is that a fully
      integrated grounded theory was unable to be produced due to sampling constraints.
      RESULTS: Four enablers for the implementation of a change in the PN role to
      include cervical screening and well women's health checks are identified in this
      study. These enablers are: GPs being willing to relinquish the role of cervical
      screener and well women's health service provider; PNs being willing to expand
      their role to include cervical screening and well women's health services;
      clients preferring a female practice nurse to meet their cervical screening and
      well women's health needs; and the presence of a culture that fosters
      interprofessional teamwork. Seven strategies for successfully implementing change
      from the perspective of PNs are also constructed from the data. This study
      additionally highlights the lack of feedback on smear quality provided to PNs
      cervical screeners and well women's health service providers. CONCLUSIONS: The
      influence of consumers on the landscape of primary care service delivery in
      Australia is of particular note in this study. Developing interprofessional teams
      that maximise each health care provider's role will be fundamental to
      comprehensive service delivery in the future.

PMID- 23145902
TI  - Significance of hepatic resection for hepatocellular carcinoma with sustained
      virological response to interferon therapy for chronic hepatitis C.
AB  - AIM: A sustained virological response (SVR) to interferon (IFN) therapy for
      chronic hepatitis C decreases but does not eliminate the risk of hepatocellular
      carcinoma (HCC). The significance of hepatectomy for HCC in patients with SVR has
      not been clarified. The short- and long-term outcomes of hepatectomy for HCC in
      patients with SVR were studied. METHODS: From 2006-2011, 69 patients with chronic
      hepatitis C underwent hepatic resection for primary HCC in our hospital. Of
      these, 12 patients (17.4%) had SVR to IFN therapy at the time of hepatectomy. The
      clinicopathological factors and long-term outcomes of these patients were
      retrospectively reviewed and were compared with those of patients without SVR.
      RESULTS: The mean time from achievement of SVR to diagnosis of HCC was 62 months
      (range, 7-174). The histological inflammation of liver parenchyma had improved
      after IFN therapy in SVR cases. The preoperative serum alanine transaminase,
      albumin and prothrombin time were significantly preserved in patients with SVR.
      Intraoperative blood loss and blood transfusion rate were lower, and recurrence
      free survival rate was significantly higher, in patients with SVR. CONCLUSION: In
      patients undergoing hepatectomy for HCC, those with SVR had better perioperative
      safety and a more favorable long-term prognosis than those without SVR.

PMID- 23145903
TI  - Risk of developmental dysplasia of the hip in breech presentation: the effect of
      successful external cephalic version.
AB  - OBJECTIVE: To evaluate the effect of successful external cephalic version on the
      incidence of developmental dysplasia of the hip (DDH) requiring treatment in
      singleton breech presentation at term. DESIGN: Observational cohort study.
      SETTING: Three large teaching hospitals in the Netherlands. POPULATION: Women
      with a singleton breech presentation of 34 weeks of gestation or more, who
      underwent an external cephalic version attempt. METHODS: We made a comparison of
      the incidence of DDH between children born in breech presentation and children
      born in cephalic presentation after a successful external cephalic version. MAIN
      OUTCOME MEASURE: The incidence of DDH requiring either conservative treatment,
      with a harness, or surgical treatment. RESULTS: A total of 498 newborns were
      included in the study, of which 40 (8%) were diagnosed with DDH and 35 required
      treatment. Multivariate analysis showed that female gender (OR 2.79, 95% CI 1.23
      6.35) and successful external cephalic version (OR 0.29, 95% CI 0.09-0.95) were
      independently associated with DDH. CONCLUSIONS: A successful external cephalic
      version is associated with a lower incidence of DDH, although a high percentage
      of children born after a successful external cephalic version still appear to
      have DDH. A larger cohort study is needed to establish the definite nature of
      this relationship. Until then, we recommend the same screening policy for infants
      born in cephalic position after a successful external cephalic version as for
      infants born in breech position.

PMID- 23145904
TI  - Compositional and mechanical properties of peanuts roasted to equivalent colors
      using different time/temperature combinations.
AB  - Peanuts in North America and Europe are primarily consumed after dry roasting.
      Standard industry practice is to roast peanuts to a specific surface color
      (Hunter L-value) for a given application; however, equivalent surface colors can
      be attained using different roast temperature/time combinations, which could
      affect product quality. To investigate this potential, runner peanuts from a
      single lot were systematically roasted using 5 roast temperatures (147, 157, 167,
      177, and 187  degrees C) and to Hunter L-values of 53 +/- 1, 48.5 +/- 1, and 43
      +/- 1, corresponding to light, medium, and dark roasts, respectively. Moisture
      contents (MC) ranged from 0.41% to 1.70% after roasting. At equivalent roast
      temperatures, MC decreased as peanuts became darker; however, for a given color,
      MC decreased with decreasing roast temperature due to longer roast times required
      for specified color formation. Initial total tocopherol contents of expressed
      oils ranged from 164 to 559 MUg/g oil. Peanuts roasted at lower temperatures and
      darker colors had higher tocopherol contents. Glucose content was roast color and
      temperature dependent, while fructose was only temperature dependent. Soluble
      protein was lower at darker roast colors, and when averaged across temperatures,
      was highest when samples were roasted at 187  degrees C. Lysine content decreased
      with increasing roast color but was not dependent on temperature. MC strongly
      correlated with several components including tocopherols (R(2) = 0.67), soluble
      protein (R(2) = 0.80), and peak force upon compression (R(2) = 0.64). The
      variation in characteristics related to roast conditions is sufficient to suggest
      influences on final product shelf life and consumer acceptability.

PMID- 23145905
TI  - Extending the TIME concept: what have we learned in the past 10 years?(*).
AB  - The TIME acronym (tissue, infection/inflammation, moisture balance and edge of
      wound) was first developed more than 10 years ago, by an international group of
      wound healing experts, to provide a framework for a structured approach to wound
      bed preparation; a basis for optimising the management of open chronic wounds
      healing by secondary intention. However, it should be recognised that the TIME
      principles are only a part of the systematic and holistic evaluation of each
      patient at every wound assessment. This review, prepared by the International
      Wound Infection Institute, examines how new data and evidence generated in the
      intervening decade affects the original concepts of TIME, and how it is
      translated into current best practice. Four developments stand out: recognition
      of the importance of biofilms (and the need for a simple diagnostic), use of
      negative pressure wound therapy (NPWT), evolution of topical antiseptic therapy
      as dressings and for wound lavage (notably, silver and polyhexamethylene
      biguanide) and expanded insight of the role of molecular biological processes in
      chronic wounds (with emerging diagnostics and theranostics). Tissue: a major
      advance has been the recognition of the value of repetitive and maintenance
      debridement and wound cleansing, both in time-honoured and novel methods (notably
      using NPWT and hydrosurgery). Infection/inflammation: clinical recognition of
      infection (and non infective causes of persisting inflammation) is critical. The
      concept of a bacterial continuum through contamination, colonisation and
      infection is now widely accepted, together with the understanding of biofilm
      presence. There has been a return to topical antiseptics to control bioburden in
      wounds, emphasised by the awareness of increasing antibiotic resistance.
      Moisture: the relevance of excessive or insufficient wound exudate and its
      molecular components has led to the development and use of a wide range of
      dressings to regulate moisture balance, and to protect peri-wound skin, and
      optimise healing. Edge of wound: several treatment modalities are being
      investigated and introduced to improve epithelial advancement, which can be
      regarded as the clearest sign of wound healing. The TIME principle remains
      relevant 10 years on, with continuing important developments that incorporate new
      evidence for wound care.

PMID- 23145906
TI  - Hind foot lameness: results of magnetic resonance imaging in 38 horses (2001
      2011).
AB  - REASONS FOR PERFORMING STUDY: The distribution of lesions detected using magnetic
      resonance imaging (MRI) of hind feet has not been reported. OBJECTIVE: To
      evaluate type and distribution of lesions detected using MRI in hind feet of lame
      horses and to compare the findings with those reported in front feet; to document
      follow-up information. METHODS: Horses were selected if hindlimb lameness was
      abolished by plantar nerve blocks performed at the base of the proximal sesamoid
      bones. Magnetic resonance images were acquired using either a low-field or a high
      field magnet, and all images were evaluated retrospectively by both authors. A
      primary diagnosis was defined as the most likely cause of lameness, based also on
      clinical findings and results of other imaging techniques. If >=3 structures were
      equally affected, the horse was classified as having multiple injuries. Follow-up
      information was collected by telephone questionnaire; outcome was classified as
      return to former level of athletic function, working at a lower level or retired.
      RESULTS: Thirty-eight horses were included. Primary collateral sesamoidean
      ligament (CSL) injury was identified in 9 horses. Nine horses had multiple
      injuries, 8 had primary bone pathology, 5 had collateral desmopathy of the distal
      interphalangeal joint, one had primary deep digital flexor tendonitis, 2 had
      navicular bone pathology and 4 had lesions involving other structures within the
      foot. Seven horses were subjected to euthanasia shortly after diagnosis; 6 as a
      result of poor prognosis and one as a result of post anaesthetic complications, 4
      of which had primary bone lesions, 2 multiple lesions and one distal
      interphalangeal joint pathology. Follow-up information was available for 24
      horses. Eleven horses returned to previous performance and 2 to a lower level of
      performance; 9 horses were retired because of recurrent lameness. Five of 8
      horses with CSL injury returned to previous performance and 2 to a lower level.
      CONCLUSIONS AND POTENTIAL RELEVANCE: Collateral sesamoidean ligament injury and
      primary bone pathology are commonly observed on MRI examination of hind feet, and
      the prognosis is reasonable.

PMID- 23145907
TI  - Ex vivo transcriptional profiling reveals a common set of genes important for the
      adaptation of Pseudomonas aeruginosa to chronically infected host sites.
AB  - The opportunistic bacterium Pseudomonas aeruginosa is a major nosocomial pathogen
      causing both devastating acute and chronic persistent infections. During the
      course of an infection, P.  aeruginosa rapidly adapts to the specific conditions
      within the host. In the present study, we aimed at the identification of genes
      that are highly expressed during biofilm infections such as in chronically
      infected lungs of patients with cystic fibrosis (CF), burn wounds and
      subcutaneous mouse tumours. We found a common subset of differentially regulated
      genes in all three in vivo habitats and evaluated whether their inactivation
      impacts on the bacterial capability to form biofilms in vitro and to establish
      biofilm-associated infections in a murine model. Additive effects on biofilm
      formation and host colonization were discovered by the combined inactivation of
      several highly expressed genes. However, even combined inactivation was not
      sufficient to abolish the establishment of an infection completely. These
      findings can be interpreted as evidence that either redundant traits encode
      functions that are essential for in vivo survival and chronic biofilm infections
      and/or bacterial adaptation is considerably achieved independently of
      transcription levels. Supplemental screens, will have to be applied in order to
      identify the minimal set of key genes essential for the establishment of chronic
      infectious diseases.

PMID- 23145908
TI  - Investigation of the association between dietary intake, disease severity and
      airway inflammation in asthma.
AB  - BACKGROUND AND OBJECTIVE: Dietary intake is an important modifiable risk factor
      for asthma and may be related to disease severity and inflammation, through the
      effects of intake of anti-oxidant-rich foods and pro-inflammatory nutrients. This
      study aimed to examine dietary intake in asthma in relation to asthma severity,
      lung function, inhaled corticosteroid use, leptin levels and inflammation.
      METHODS: Food frequency questionnaires, spirometry and hypertonic saline
      challenge were completed by 137 stable asthmatics and 65 healthy controls. Plasma
      leptin was analysed by immunoassay. Induced sputum differential cell counts were
      determined. RESULTS: Subjects with severe persistent asthma consumed more fat and
      less fibre as compared with healthy controls (odds ratio 1.04 (95% confidence
      interval: 1.01-1.07), P = 0.014) (odds ratio 0.94 (95% confidence interval: 0.90
      0.99), P = 0.018). Among asthmatics, higher fat and lower fibre intakes were
      associated with lower forced expiratory volume in 1 s and airway eosinophilia.
      Leptin levels were increased in both male and female asthmatics as compared with
      healthy controls. No association existed among asthmatics between corticosteroid
      use and dietary intake. CONCLUSIONS: It was found that asthmatics within the
      subgroup of severe persistent asthma have a different pattern of dietary intake
      as compared with healthy controls, which was associated with lower lung function
      and increased airway inflammation.

PMID- 23145909
TI  - Brominated aromatic furanones and related esters from the ascidian Synoicum sp.
AB  - Nine new compounds, tris-aromatic furanones (1, 2, 3a, 3b, and 4) and related bis
      aromatic diesters (5a, 5b, 6a, and 6b), are described from the ascidian Synoicum
      sp. collected off the coast of Chuja-do, Korea. The structures of these
      compounds, designated as cadiolides E and G-I (1-4) and synoilides A and B (5 and
      6), were determined by extensive spectroscopic analyses. The absolute
      configuration at the asymmetric center of cadiolide G (2) was assigned by ECD
      analysis. Of these new compounds, cadiolide I and the synoilides possess
      unprecedented carbon skeletons. Several of these compounds exhibited significant
      inhibition against diverse bacterial strains as well as moderate inhibition
      against the enzymes sortase A, isocitrate lyase, and Na(+)/K(+)-ATPase.

PMID- 23145910
TI  - Bis-silylation of Lu3N@I(h)-C80: considerable variation in the electronic
      structures.
AB  - Photochemical reactions of Lu(3)N@I(h)-C(80) with disiliranes 1 and 2 produce
      several isomeric adducts. Spectroscopic analyses characterize the most stable
      isomers as 1,4(AA) adducts, which consist of paired twist conformers at rt. The
      electrochemical and theoretical studies reveal that the HOMO-LUMO energy gaps of
      the 1,4(AA) adducts are smaller than that of Lu(3)N@I(h)-C(80) because the
      electron-donating groups effectively raise the HOMO levels.

PMID- 23145911
TI  - Design and synthesis of a luminescent cyclometalated iridium(III) complex having
      N,N-diethylamino group that stains acidic intracellular organelles and induces
      cell death by photoirradiation.
AB  - Cyclometalated iridium(III) complexes have received considerable attention and
      are important candidates for use as luminescent probes for cellular imaging
      because of their potential photophysical properties. We previously reported that
      fac-Ir(atpy)(3)4 (atpy = 2-(5'-amino-4'-tolyl)pyridine) containing three amino
      groups at the 5'-position of the atpy ligand shows a maximum red emission (at
      around 600 nm) under neutral and basic conditions and a green emission (at 531
      nm) at acidic pH (pH 3-4). In this Article, we report on the design and synthesis
      of a new pH-sensitive cyclometalated Ir(III) complex containing a 2-(5'-N,N
      diethylamino-4'-tolyl)pyridine (deatpy) ligand, fac-Ir(deatpy)(3)5. The complex
      exhibits a considerable change in emission intensity between neutral and slightly
      acidic pH (pH 6.5-7.4). Luminescence microscopic studies using HeLa-S3 cells
      indicate that 5 can be used to selectively stain lysosome, an acidic organelle in
      cells. Moreover, complex 5 is capable of generating singlet oxygen in a pH
      dependent manner and inducing the death of HeLa-S3 cells upon photoirradiation at
      377 or 470 nm.

PMID- 23145913
TI  - Highly regio-, diastereo-, and enantioselective 1,6- and 1,8-additions of
      azlactones to di- and trienyl N-acylpyrroles.
AB  - A vinylog of Michael addition (1,6-addition) of azlactones to delta-substituted
      dienyl N-acylpyrroles has been developed with virtually complete 1,6-, diastereo
      , and enantioselectivities by means of chiral P-spiro triaminoiminophosphorane as
      a catalyst. This system has been successfully extended to an unprecedented bis
      vinylog of Michael addition (1,8-addition) of azlactones to zeta-substituted
      trienyl N-acylpyrroles with high levels of regio- and stereocontrol.

PMID- 23145914
TI  - ChIP-Chip Identifies SEC23A, CFDP1, and NSD1 as TFII-I Target Genes in Human
      Neural Crest Progenitor Cells.
AB  - Objectives :  GTF2I and GTF2IRD1 genes located in Williams-Beuren syndrome (WBS)
      critical region encode TFII-I family transcription factors. The aim of this study
      was to map genomic sites bound by these proteins across promoter regions of
      developmental regulators associated with craniofacial development. Design : 
      Chromatin was isolated from human neural crest progenitor cells and the DNA
      binding profile was generated using the human RefSeq tiling promoter ChIP-chip
      arrays. Results :  TFII-I transcription factors are recruited to the promoters of
      SEC23A, CFDP1, and NSD1 previously defined as TFII-I target genes. Moreover, our
      analysis revealed additional binding elements that contain E-boxes and initiator
      like motifs. Conclusions :  Genome-wide promoter binding studies revealed SEC23A,
      CFDP1, and NSD1 linked to craniofacial or dental development as direct TFII-I
      targets. Developmental regulation of these genes by TFII-I factors could
      contribute to the WBS-specific facial dysmorphism.

PMID- 23145915
TI  - Fragmented adipose tissue transplanted to craniofacial deformities induces bone
      repair associated with immunoexpression of adiponectin and parathyroid hormone 1
      receptor.
AB  - Objective : This study analyzed the influence of autogenous white adipose tissue
      on bone matrix development in critical-size defects created in rabbit calvaria.
      Materials and methods : A 15-mm-diameter defect was created in the calvaria of 42
      rabbits. Twenty-one rabbits were treated with 86 mm(3) of immediate transplant of
      fragmented white subcutaneous adipose tissue (WSAT); the others constituted the
      control group (sham). The animals were euthanized at 7, 15, and 40 days
      postsurgery (n = 7), and the histological data were analyzed by histomorphometry
      and immunohistochemistry using the anti-adiponectin and parathyroid hormone 1
      receptor (PTH1R) antibodies. Results : The calvariae treated with fragmented WSAT
      demonstrated significant bone formation. These results coincided with the
      significant presence of immunopositivity to adiponectin and PTH1R in loci, which
      in turn coincided with the increase in bonelike matrix deposited both in fat
      tissue stroma and adipocytes' cytoplasm. In contrast, the control group revealed
      a small amount of bone-matrix deposition and presented scarce PTH1R expression
      and a lack of immunostain for adiponectin. Conclusion : These results indicate
      that transplant of fragmented white subcutaneous adipose tissue may be an
      alternative to treatment of craniofacial bone deformities because adipose tissue
      suffers from osseous metaplasia and exhibits immunoexpression of the adiponectin
      and PTH1R, which are proteins associated with bone metabolism. 

PMID- 23145912
TI  - Active transposition in genomes.
AB  - Transposons are DNA sequences capable of moving in genomes. Early evidence showed
      their accumulation in many species and suggested their continued activity in at
      least isolated organisms. In the past decade, with the development of various
      genomic technologies, it has become abundantly clear that ongoing activity is the
      rule rather than the exception. Active transposons of various classes are
      observed throughout plants and animals, including humans. They continue to create
      new insertions, have an enormous variety of structural and functional impact on
      genes and genomes, and play important roles in genome evolution. Transposon
      activities have been identified and measured by employing various strategies.
      Here, we summarize evidence of current transposon activity in various plant and
      animal genomes.

PMID- 23145916
TI  - Short communication: proangiogenic hematopoietic cells in acute HIV infection.
AB  - Chronic HIV infection induces significant changes in the trafficking of
      circulating endothelial progenitor cells (EPCs). Specifically, it causes marked
      depletion of proangiogenic hematopoietic cells, the so-called colony-forming unit
      endothelial cells (CFU-ECs). In this study we evaluated CFU-ECs in two subjects
      with acute HIV infection. We found that both patients already had a low CFU-EC
      level at the time of diagnosis. Nevertheless, after 6 months of antiretroviral
      therapy, the CFU-EC concentration reverted to normal values in both cases. HIV
      significantly depletes the CFU-EC compartment even in the early phase of
      infection, while 6-month therapy appears to be able to restore it.

PMID- 23145917
TI  - Liver transplantation in a patient acutely infected with pandemic influenza A
      H1N1.

PMID- 23145918
TI  - Glottal configuration in unilaterally paralyzed larynx and vocal function.
AB  - CONCLUSIONS: Three different types of glottal configuration in unilaterally
      paralyzed larynx were proposed by utilizing three-dimensional computed
      tomographic (3DCT) images. This new classification might facilitate understanding
      of the behavior of the affected vocal fold in terms of vocal function.
      OBJECTIVES: To develop a classification of glottal configuration in unilateral
      vocal fold paralysis (UVFP) based on the thickness and location of the vocal
      folds utilizing 3DCT and to compare each type of configuration with vocal
      function. METHODS: Thirty-seven consecutive patients with UVFP underwent CT
      during phonation and inhalation. 3D endoscopic and coronal images on two
      occasions were produced. Maximum phonation time and mean airflow rate were also
      measured. RESULTS: Three types of glottal configuration were proposed. The
      thickness of the affected vocal fold during phonation was equal to or slightly
      thinner than the healthy fold in 10 patients (type A). The affected fold of the
      remaining 27 was thin during phonation; they were further classified into types B
      and C. In type B, the affected fold remained thin during phonation and inhalation
      (n = 12). Type C was allocated to those showing one or two paradoxical movements
      of the affected fold (n = 15). Those with type A showed significantly better
      vocal function.

PMID- 23145919
TI  - In vitro effect of clinical propofol concentrations on platelet aggregation.
AB  - The inhibitory effect of propofol on platelet aggregation remains unclear, and
      studies on the subject disagree. Furthermore, although propofol infusions are
      widely used for general anesthesia and as sedatives for patients in intensive
      care units, little information is available on its concentration- and time
      related effects on platelet aggregation. Here, the authors investigated the in
      vitro effect of propofol, at concentrations required for sedation and general
      anesthesia, on platelet aggregation after 1, 2, or 3 h. Blood from healthy
      volunteers (n = 9) was incubated at propofol plasma concentrations of 0, 2, 4,
      and 10 MUg/mL in a water bath at 37 degrees C. Platelet aggregation was measured
      using a platelet function analyzer (PFA-100) after 1, 2, or 3 h of incubation.
      Times to occlude collagen/epinephrine (CEPI) or collagen/adenosine 5'-diphosphate
      (CADP)-coated membranes (closure times, CTs) were measured. The CEPI and CADP CTs
      of non-incubated blood were 125.6 +/- 19.5 s and 93.0 +/- 12.2 s, respectively,
      and no significant difference in CEPI CTs was observed at propofol plasma
      concentrations of 0, 2, 4, and 10 MUg/mL after incubation for 1, 2, or 3 h. CADP
      CTs were comparable at propofol concentrations of 0, 2, 4, and 10 MUg/mL at each
      incubation time. These findings suggest that propofol at concentrations required
      for sedation and general anesthesia has no inhibitory effect on platelet
      aggregation after 3 h of incubation.

PMID- 23145920
TI  - Polymer micelle with pH-triggered hydrophobic-hydrophilic transition and de-cross
      linking process in the core and its application for targeted anticancer drug
      delivery.
AB  - In this study, an novel amphiphilic block copolymer P[PEGMA-b-(DEMA-co-APMA)]-FA
      and its cross-linker uracil-(CH2)6-uracil (U-(CH2)6-U) were synthesized and used
      as the targeted and pH-responsive nanocarriers for anticancer drug delivery. The
      hydrophobic block of the copolymer contains adenine (A) and tertiary amine
      moieties and the hydrophilic block is terminated with a targeting ligand folic
      acid (FA). Under neutral pH, the hydrophobic chain segments of the copolymer are
      cross-linked by U-(CH2)6-U through the A-U nucleobase pairing based on
      complementary multiple hydrogen bonding, and the copolymer forms stable micelles
      with their mean diameter of around 170 nm in water. While under acidic pH, the
      micelles dissociate as a result of protonation of tertiary amines and disruption
      of the A-U nucleobase pairing. Flow cytometry and fluorescent microscope
      observation show that, when loaded with an anticancer drug DOX, the micelles can
      preferably enter folate receptor (FR)-positive cancer cells and kill the cells
      via intracellular release of the anticancer drug. Cytotoxicity tests (MTT tests)
      indicate that the micelles with FA on their surfaces exhibit higher cytotoxicity
      toward FR-positive cells than those without FA. This study provides useful
      insights on designing and improving the applicability of copolymer micelles for
      other targeted drug delivery systems.

PMID- 23145921
TI  - Photophysical properties of MM quadruply bonded complexes supported by
      carboxylate ligands, MM = Mo2, MoW, or W2.
AB  - While chemists have extensively studied the photophysical properties of d(6),
      d(8), and d(10) transition metal complexes, their early transition metal
      counterparts have received less attention. Quadruply bonded complexes of
      molybdenum and tungsten supported by carboxylate ligands have intense metal-to
      ligand charge transfer (MLCT) absorptions that arise from the electronic coupling
      of the metal-metal (MM) delta orbital with the CO(2) pi-system. This coupling may
      in turn be linked to an extended pi-conjugated organic functional group. The
      major interaction is akin to the so-called back-bonding in metal carbonyl
      complexes. By the appropriate selection of MM, its attendant ligands, and the
      organic group, this absorption can be tuned to span the visible and near IR
      range, from 400 to 1000 nm. Consequently, these complexes offer potential as
      photon harvesters for photovoltaic devices and photocatalysis.  In this Account,
      we describe recent studies of dinuclear M(II) containing complexes, where M = Mo
      or W, and show that there are both parallels and disparities to the monomeric
      transition metal complexes. These early transition metal complexes have
      relatively long lived excited state singlets when compared to other transition
      metal complexes. They also often show unusual dual emission (fluorescence and
      phosphorescence), with singlet (S(1)) lifetimes that range from 1 to 20 ps, and
      triplet (T(1)) lifetimes from 3 ns to 200 MUs. The fluorescent S(1) states are
      typically (1)MLCT for both M = Mo and W. These extended singlet lifetimes are
      uncommon for mononuclear transition metal complexes, which typically have very
      short lived (1)MLCT states due to rapid femto-second intersystem crossing rates.
      However, the T(1) states differ. This phosphorescence is MLCT in nature when M =
      W, while this emission comes from the deltadelta* state for M = Mo. Through time
      resolved femtosecond infrared spectroscopy, we can detect the asymmetric stretch
      of the CO(2) ligand in both the singlet and triplet deltadelta* states. Through
      these analytical methods, we can study how the charge distribution in the singlet
      and triplet excited states changes over time. In addition, we can detect
      delocalized or localized examples of MLCT states, which represent class III and I
      excited state mixed valence in the Robin and Day scheme.

PMID- 23145922
TI  - Pharmaceutical care issues identified by pharmacists in patients with diabetes,
      hypertension or hyperlipidaemia in primary care settings.
AB  - BACKGROUND: The roles of pharmacists have evolved from product oriented,
      dispensing of medications to more patient-focused services such as the provision
      of pharmaceutical care. Such pharmacy service is also becoming more widely
      practised in Malaysia but is not well documented. Therefore, this study is
      warranted to fill this information gap by identifying the types of pharmaceutical
      care issues (PCIs) encountered by primary care patients with diabetes mellitus,
      hypertension or hyperlipidaemia in Malaysia. METHODS: This study was part of a
      large controlled trial that evaluated the outcomes of multiprofessional
      collaboration which involved medical general practitioners, pharmacists,
      dietitians and nurses in managing diabetes mellitus, hypertension and
      hyperlipidaemia in primary care settings. A total of 477 patients were recruited
      by 44 general practitioners in the Klang Valley. These patients were counselled
      by the various healthcare professionals and followed-up for 6 months. RESULTS: Of
      the 477 participants, 53.7% had at least one PCI, with a total of 706 PCIs. These
      included drug-use problems (33.3%), insufficient awareness and knowledge about
      disease condition and medication (20.4%), adverse drug reactions (15.6%),
      therapeutic failure (13.9%), drug-choice problems (9.5%) and dosing problems
      (3.4%). Non-adherence to medications topped the list of drug-use problems,
      followed by incorrect administration of medications. More than half of the PCIs
      (52%) were classified as probably clinically insignificant, 38.9% with minimal
      clinical significance, 8.9% as definitely clinically significant and could cause
      patient harm while one issue (0.2%) was classified as life threatening. The main
      causes of PCIs were deterioration of disease state which led to failure of
      therapy, and also presentation of new symptoms or indications. Of the 338 PCIs
      where changes were recommended by the pharmacist, 87.3% were carried out as
      recommended. CONCLUSIONS: This study demonstrates the importance of pharmacists
      working in collaboration with other healthcare providers especially the medical
      doctors in identifying and resolving pharmaceutical care issues to provide
      optimal care for patients with chronic diseases.

PMID- 23145924
TI  - Phenolics and their antifungal role in grapevine wood decay: focus on the
      Botryosphaeriaceae family.
AB  - The interaction between  Vitis vinifera  and trunk disease fungi requires better
      understanding. We studied the role of phenolics as possible plant defense
      compounds in this context. The impact of 24 grapevine phenolic compounds was
      determined on 6 major wood decay fungi by an in vitro agar plate assay.
      Hydroxystilbenoids, especially oligomers such as miyabenol C, isohopeaphenol, and
      vitisin A and B, greatly reduced the growth of the fungi, except that of 
      Phaeoacremonium aleophilum . A detailed investigation in 10 Botryosphaeriaceae
      strains revealed that all of the studied members of this family display a common
      susceptibility to phenolics that is more or less significant. Then we undertook a
      quantitative analysis of stilbenoid content in grapevine plantlets inoculated
      with Botryosphaeriaceae to investigate whether in planta these fungi have to
      counteract the most active phenolics. On the basis of our results, the possible
      role of phenolics in grapevine defense against trunk disease agents is discussed.

PMID- 23145923
TI  - Sphingosine and FTY720 are potent inhibitors of the transient receptor potential
      melastatin 7 (TRPM7) channels.
AB  - BACKGROUND AND PURPOSE: Transient receptor potential melastatin 7 (TRPM7) is a
      unique channel kinase which is crucial for various physiological functions.
      However, the mechanism by which TRPM7 is gated and modulated is not fully
      understood. To better understand how modulation of TRPM7 may impact biological
      processes, we investigated if TRPM7 can be regulated by the phospholipids
      sphingosine (SPH) and sphingosine-1-phosphate (S1P), two potent bioactive
      sphingolipids that mediate a variety of physiological functions. Moreover, we
      also tested the effects of the structural analogues of SPH, N,N-dimethyl-D
      erythro-sphingosine (DMS), ceramides and FTY720 on TRPM7. EXPERIMENTAL APPROACH:
      HEK293 cells stably expressing TRPM7 were used for whole-cell, single-channel and
      macropatch current recordings. Cardiac fibroblasts were used for native TRPM7
      current recording. KEY RESULTS: SPH potently inhibited TRPM7 in a concentration
      dependent manner, whereas S1P and other ceramides did not produce noticeable
      effects. DMS also markedly inhibited TRPM7. Moreover, FTY720, an
      immunosuppressant and the first oral drug for treatment of multiple sclerosis,
      inhibited TRPM7 with a similar potency to that of SPH. In contrast, FTY720-P has
      no effect on TRPM7. It appears that SPH and FTY720 inhibit TRPM7 by reducing
      channel open probability. Furthermore, endogenous TRPM7 in cardiac fibroblasts
      was markedly inhibited by SPH, DMS and FTY720. CONCLUSIONS AND IMPLICATIONS: This
      is the first study demonstrating that SPH and FTY720 are potent inhibitors of
      TRPM7. Our results not only provide a new modulation mechanism of TRPM7, but also
      suggest that TRPM7 may serve as a direct target of SPH and FTY720, thereby
      mediating S1P-independent physiological/pathological functions of SPH and FTY720.

PMID- 23145925
TI  - Predictors of first-line antiretroviral therapy discontinuation due to drug
      related adverse events in HIV-infected patients: a retrospective cohort study.
AB  - BACKGROUND: Drug-related toxicity has been one of the main causes of
      antiretroviral treatment discontinuation. However, its determinants are not fully
      understood. Aim of this study was to investigate predictors of first-line
      antiretroviral therapy discontinuation due to adverse events and their evolution
      in recent years. METHODS: Patients starting first-line antiretroviral therapy
      were retrospectively selected. Primary end-point was the time to discontinuation
      of therapy due to adverse events, estimating incidence, fitting Kaplan-Meier and
      multivariable Cox regression models upon clinical/demographic/chemical baseline
      patients' markers. RESULTS: 1,096 patients were included: 302 discontinuations
      for adverse events were observed over 1,861 person years of follow-up between
      1988 and 2010, corresponding to an incidence (95% CI) of 0.16 (0.14-0.18). By
      Kaplan-Meier estimation, the probabilities (95% CI) of being free from an adverse
      event at 90 days, 180 days, one year, two years, and five years were 0.88 (0.86
      0.90), 0.85 (0.83-0.87), 0.79 (0.76-0.81), 0.70 (0.67-0.74), 0.55 (0.50-0.61),
      respectively. The most represented adverse events were gastrointestinal symptoms
      (28.5%), hematological (13.2%) or metabolic (lipid and glucose metabolism,
      lipodystrophy) (11.3%) toxicities and hypersensitivity reactions (9.3%). Factors
      associated with an increased hazard of adverse events were: older age, CDC stage
      C, female gender, homo/bisexual risk group (vs. heterosexual), HBsAg-positivity.
      Among drugs, zidovudine, stavudine, zalcitabine, didanosine, full-dose ritonavir,
      indinavir but also efavirenz (actually recommended for first-line regimens) were
      associated to an increased hazard of toxicity. Moreover, patients infected by HIV
      genotype F1 showed a trend for a higher risk of adverse events. CONCLUSIONS:
      After starting antiretroviral therapy, the probability of remaining free from
      adverse events seems to decrease over time. Among drugs associated with increased
      toxicity, only one is currently recommended for first-line regimens but with
      improved drug formulation. Older age, CDC stage, MSM risk factor and gender are
      also associated with an increased hazard of toxicity and should be considered
      when designing a first-line regimen.

PMID- 23145926
TI  - Role of sorafenib in the treatment of advanced hepatocellular carcinoma: An
      update.
AB  - Sorafenib is the first and only p.o. administrated drug currently approved to
      treat advanced hepatocellular carcinoma (HCC). However, concerns have been raised
      about sorafenib therapy, including acquired drug resistance. This review provides
      an overview of sorafenib in the treatment of HCC on the basis of data obtained in
      the laboratory and in clinical studies. Three underlying mechanisms have been
      found to support sorafenib therapy. First, sorafenib blocks HCC cell
      proliferation by inhibiting BRaf and Raf1/c-Raf serine/threonine kinase
      phosphorylation in the mitogen-activated protein kinase pathway. Second,
      sorafenib induces apoptosis by reducing elF4E phosphorylation and downregulating
      Mcl-1 levels in tumor cells. Third, sorafenib prevents tumor-associated
      angiogenesis by inactivating vascular endothelial growth factor receptors (VEGFR
      2 and -3) and the platelet-derived growth factor receptor-beta. Clinical trials
      have demonstrated the effectiveness and relative safety of sorafenib, and thus
      the drug is used in unresectable HCC. However, many patients may develop acquired
      resistance to sorafenib, so their response to sorafenib is eventually lost.
      Sorafenib may induce autophagy, which leads to apoptosis. However, autophagy can
      also cause drug resistance. Many studies have combined sorafenib with other
      treatments in an effort to increase its effects, reduce the necessary dose or
      overcome resistance. It is urgent to study the mechanisms underlying how
      sorafenib interacts with cellular molecules and other drugs to increase its
      efficacy and reduce resistance in HCC patients.

PMID- 23145927
TI  - Clinical trials evaluating pathogen-reduced platelet products: methodologic
      issues and recommendations.
AB  - BACKGROUND: Several randomized trials of platelet (PLT) products have been
      conducted with different study designs, endpoints, and analyses. The purpose of
      this article is to discuss methodologic issues in the design and analysis of PLT
      transfusion trials evaluating pathogen reduction technology and make
      recommendations for the conduct of future trials. STUDY DESIGN AND METHODS: Six
      randomized clinical trials of pathogen-inactivated PLT products are reviewed and
      associated methodologic issues are discussed. RESULTS: The variation in the trial
      designs, outcomes, and methods of analysis suggest the need to harmonize the way
      trials of pathogen-reduced PLT products are conducted to facilitate comparisons
      between studies and the synthesis of results. Recommendations are made with this
      goal in mind and to increase the rigor and relevance of findings from future
      trials. CONCLUSIONS: Future randomized trials of pathogen-reduced PLT products
      should be based on a clearly stated hypothesis driven by an important research
      question, a design that is optimal for the research question, outcomes that
      relate to the research question, clearly defined observation periods, and
      statistical analyses that lead to valid tests of these hypotheses and associated
      estimates of treatment effect.

PMID- 23145928
TI  - Tea polyphenols modulate antioxidant redox system on cisplatin-induced reactive
      oxygen species generation in a human breast cancer cell.
AB  - Tea polyphenols (TPP) have potent antioxidant and anticancer properties,
      particularly in patients undergoing radiation or chemotherapy. However, few
      studies have been conducted on treatments using a combination of TPP and the
      conventional chemical anticancer drug cisplatin (CP). This study was designed to
      investigate the mechanism of the cytotoxicity of total TPP and CP, which may
      synergistically induce cell death in cancer cells. Here, breast cancer cells (MCF
      7) were treated with various concentrations of TPP alone or in combination with
      the chemotherapeutic drug CP. The effect of TPP on cell growth, intracellular
      reactive oxygen species (ROS) level, apoptosis and gene expression of caspase-3,
      caspase-8 and caspase-9 and p53 was investigated. The MTT (3-(4,5-Dimethylthiazol
      2-yl)-2,5-diphenyltetrazolium bromide) assay revealed that the MCF-7 cells were
      less sensitive to growth inhibition by TPP treatment than either CP or the
      combination therapy. Propidium iodide nuclear staining indicated that exposure to
      this combination increased the proportion of apoptotic nuclei compared with a
      single-agent treatment. Flow cytometry analysis was used to quantify changes in
      intracellular ROS. Detection of activated caspases by fluorescently labelled
      inhibitors of caspases (FLICA) combined with the plasma membrane permeability
      assay demonstrated that the percentage of early and late apoptotic/secondary
      necrotic cells was higher in the cells treated with the combination than in those
      treated with either TPP or CP alone. The combined TPP and CP treatment
      synergistically induced apoptosis through both caspase-8 and caspase-9 activation
      and p53 over-expression. This suggests that TPP plus CP may be used as an
      efficient antioxidant-based combination therapy for estrogen receptor (ER)
      positive and p53-positive breast cancer.

PMID- 23145929
TI  - The outcome of pregnancies in women with cystic fibrosis--single centre
      experience 1998-2011.
AB  - OBJECTIVE: To describe the maternal and fetal outcomes of pregnancies in women
      with cystic fibrosis. DESIGN: Retrospective study. SETTING: Single obstetric
      hospital and adult cystic fibrosis centre. METHODS: Retrospective case-note
      review of pregnant women with cystic fibrosis referred for antenatal care and
      delivery. MAIN OUTCOME MEASURES: Maternal and fetal outcomes, mode of delivery,
      lung function and pregnancy complications. RESULTS: Forty-eight pregnancies were
      studied in 41 women. There were two miscarriages, 44 singleton pregnancies and
      two sets of twins. All babies were liveborn and survived. The mean gestational
      age at delivery was 35.9 +/- 3.3 weeks. There were no fetal abnormalities or
      terminations of pregnancy. The median birthweight centile was 31.9 (interquartile
      range 14.9-55.6). Twenty-five (52.1%) of the women had pancreatic insufficiency
      and 17 (35.4%) required insulin. There was a positive correlation between booking
      predicted forced expiratory volume in 1 second (FEV(1) ) and gestational age at
      delivery (P < 0.01). Women with FEV(1) <=60% were more likely to deliver earlier
      and by caesarean section compared with women with FEV(1) >60% (35.0 +/- 3.2 weeks
      versus 37.1 +/- 3.0 weeks; P = 0.02 and 75.0% versus 25.0%; P = 0.01). Three of
      the seven women with an FEV(1) <40% died within 18 months of delivery. Four of
      the eight women with FEV(1) 40-50% died between 2 and 8 years after delivery.
      CONCLUSION: Pregnancy for women with cystic fibrosis is possible and results in
      favourable maternal and fetal outcomes, but the incidence of preterm delivery and
      caesarean section is increased. Women with pre-existing poor lung function should
      be counselled antenatally to ensure that they understand the implications of
      their shortened life-expectancy and parenthood.

PMID- 23145930
TI  - Immunoglobulin G4-related lung disease: clinicoradiological and pathological
      features.
AB  - BACKGROUND AND OBJECTIVE: Immunoglobulin G4 (IgG4)-related disease is a multi
      organ disorder that can include the lungs. IgG4-related lung disease can present
      in various forms; the clinical, radiological and pathological features of
      patients with this disease have been assessed. METHODS: Forty-eight patients
      suspected of having IgG4-related lung disease, with a high serum concentration of
      IgG4 and abundant IgG4-positive plasma cell infiltration into the intrathoracic
      organs, were retrospectively evaluated. Their clinical features, chest imaging
      findings and pathological findings were examined, with final diagnoses made by an
      open panel conference. RESULTS: Of the 48 patients, 18 with extrathoracic
      manifestations were diagnosed as having IgG4-related lung disease. Most of these
      patients were middle-aged to elderly men. IgG4-related lung disease was
      characterized by high serum concentrations of IgG and IgG4, normal white blood
      cell count and serum C-reactive protein concentration and a good response to
      corticosteroids. Common radiological findings included mediastinal
      lymphadenopathy and thickening of the perilymphatic interstitium, with or without
      subpleural and/or peribronchovascular consolidation. Pathological examination
      showed massive lymphoplasmacytic infiltration with fibrosis in and around the
      lymphatic routes, with distribution well correlated with radiological
      manifestations. CONCLUSIONS: The findings suggest that the intrathoracic
      manifestations of IgG4-related lung disease develop through lymphatic routes of
      the lungs and show various clinical characteristics. Because some
      lymphoproliferative disorders show similar findings, the correlation of
      clinicoradiological and pathological characteristics is crucial for the diagnosis
      of IgG4-related lung disease.

PMID- 23145931
TI  - Synovial folds in equine articular process joints.
AB  - REASONS FOR PERFORMING STUDY: Cervical synovial folds have been suggested as a
      potential cause of neck pain in humans. Little is known about the extent and
      characteristics of cervical synovial folds in horses. OBJECTIVES: The objective
      of this explorative study was to determine the frequency of synovial folds in
      equine cervical articular process joints and to provide a characterisation of the
      size and morphology of the synovial folds. METHODS: Equine cervical articular
      process joints from 6 horses were included in the study, ranging from cervical
      vertebra 2 (C2) to cervical vertebra 7 (C7) bilaterally. The articular process
      joints were dissected, and the cranial and caudal synovial folds of each joint
      were measured and embedded in paraffin. Synovial folds were analysed
      histologically and classified according to type, as adipose, fibrous and mixed
      type. Factors potentially influencing fold size were investigated, including
      joint number (from C2/C3 to C6/C7), fold type, position of fold within the joint
      (cranial or caudal) and side of neck (right or left). RESULTS: Synovial folds
      were identified in 98% of cervical articular process joints examined. The width
      of the synovial folds varied from 4 to 41 mm, and the height from 1 to 17.8 mm.
      Thirty-eight per cent of the synovial folds were of adipose type, 41% of fibrous
      type and 21% of mixed type. Synovial fold size was significantly influenced by
      the side of the neck and fold type. CONCLUSIONS AND POTENTIAL RELEVANCE: This
      study provides a characterisation of the frequency, size and morphology of equine
      cervical synovial folds in 6 horses. Synovial folds were present in 98% of the
      cervical articular process joints examined, and the size of the synovial folds
      indicates that they could be damaged by acute injury or chronic disease in the
      cervical articular process joints.

PMID- 23145932
TI  - Curcuminoids block TGF-beta signaling in human breast cancer cells and limit
      osteolysis in a murine model of breast cancer bone metastasis.
AB  - Effects of curcuminoids on breast cancer cell secretion of the bone-resorptive
      peptide parathyroid hormone-related protein (PTHrP) and on lytic breast cancer
      bone metastasis were evaluated. In vitro, transforming growth factor (TGF)-beta
      stimulated PTHrP secretion was inhibited by curcuminoids (IC50 = 24 MUM) in MDA
      MB-231 human breast cancer cells independent of effects on cell growth
      inhibition. Effects on TGF-beta signaling revealed decreases in phospho-Smad2/3
      and Ets-1 protein levels with no effect on p-38 MAPK-mediated TGF-beta signaling.
      In vivo, mice were inoculated with MDA-MB-231 cells into the left cardiac
      ventricle and treated ip every other day with curcuminoids (25 or 50 mg/kg) for
      21 days. Osteolytic bone lesion area was reduced up to 51% (p < 0.01). Consistent
      with specific effects on bone osteolysis, osteoclast number at the bone-tumor
      interface was reduced up to 53% (p < 0.05), while tumor area within bone was
      unaltered. In a separate study, tumor mass in orthotopic mammary xenografts was
      also unaltered by treatment. These data suggest that curcuminoids prevent TGF
      beta induction of PTHrP and reduce osteolytic bone destruction by blockade of
      Smad signaling in breast cancer cells.

PMID- 23145933
TI  - The impact of cell source, culture methodology, culture location, and individual
      donors on gene expression profiles of bone marrow-derived and adipose-derived
      stromal cells.
AB  - Bone marrow (BM) stromal cells (MSCs), also known as mesenchymal stem cells,
      display a high degree of heterogeneity. To shed light on the causes of this
      heterogeneity, MSCs were collected from either human BM (n=5) or adipose tissue
      (AT) (n=5), and expanded using 2 different culture methods: one based on fetal
      calf serum, and one based on human platelet lysate. After initial expansion, MSCs
      were frozen, and the vials were transported to 3 different laboratories and grown
      for 1 passage using the same brand of culture plastic, medium, and supplements.
      Subsequently, the cells were harvested and assayed for their gene expression
      profile using the Affymetrix exon microarray platform. Based on gene expression
      profiles, the most discriminative feature was the anatomical harvesting site,
      followed by culture methodology. Remarkably, genes in the WNT pathway were
      expressed at higher levels in BM-derived MSCs than in AT-derived MSCs. Although
      differences were found between laboratories, cell culture location only slightly
      affects heterogeneity. Furthermore, individual donors contributed marginally to
      the observed differences in transcriptomes. Finally, BM-derived MSCs displayed
      the highest level of similarity, irrespective their culture conditions, when
      compared to AT-derived cells.

PMID- 23145934
TI  - Transcriptional analysis of rat photoreceptor cells reveals daily regulation of
      genes important for visual signaling and light damage susceptibility.
AB  - Photoreceptor cells face the challenge of adjusting their function and, possibly,
      their susceptibility to light damage to the marked daily changes in ambient light
      intensity. To achieve a better understanding of photoreceptor adaptation at the
      transcriptional level, this study aimed to identify genes which are under daily
      regulation in photoreceptor cells using microarray analysis and quantitative PCR.
      Included in the gene set obtained were a number of genes which up until now have
      not been shown to be expressed in photoreceptor cells, such as Atf3 (activating
      transcription factor 3) and Pde8a (phosphodiesterase 8A), and others with a known
      impact on phototransduction and/or photoreceptor survival, such as Grk1 (G
      protein-coupled receptor kinase 1) and Pgc-1alpha (peroxisome proliferator
      activated receptor gamma, coactivator 1alpha). According to their daily dynamics,
      the genes identified could be clustered in two groups: those with peak expression
      during the second part of the day which are uniformly promoted to cycle by
      light/dark transitions and those with peak expression during the second part of
      the night which are predominantly driven by a clock. Since Grk1 and Pgc-1alpha
      belong in the first group, the present results support a concept in which
      transcriptional regulation of genes by ambient light contributes to the
      functional adjustment of photoreceptor cells over the 24-h period.

PMID- 23145935
TI  - Rules of engagement: molecular insights from host-virus arms races.
AB  - Mammalian genes and genomes have been shaped by ancient and ongoing challenges
      from viruses. These genetic imprints can be identified via evolutionary analyses
      to reveal fundamental details about when (how old), where (which protein
      domains), and how (what are the functional consequences of adaptive changes) host
      virus arms races alter the proteins involved. Just as extreme amino acid
      conservation can serve to identify key immutable residues in enzymes, positively
      selected residues point to molecular recognition interfaces between host and
      viral proteins that have adapted and counter-adapted in a long series of
      classical Red Queen conflicts. Common rules for the strategies employed by both
      hosts and viruses have emerged from case studies of innate immunity genes in
      primates. We are now poised to use these rules to transition from a retrospective
      view of host-virus arms races to specific predictions about which host genes face
      pathogen antagonism and how those genetic conflicts transform host and virus
      evolution.

PMID- 23145936
TI  - A new view of electrochemistry at highly oriented pyrolytic graphite.
AB  - Major new insights on electrochemical processes at graphite electrodes are
      reported, following extensive investigations of two of the most studied redox
      couples, Fe(CN)(6)(4-/3-) and Ru(NH(3))(6)(3+/2+). Experiments have been carried
      out on five different grades of highly oriented pyrolytic graphite (HOPG) that
      vary in step-edge height and surface coverage. Significantly, the same
      electrochemical characteristic is observed on all surfaces, independent of
      surface quality: initial cyclic voltammetry (CV) is close to reversible on
      freshly cleaved surfaces (>400 measurements for Fe(CN)(6)(4-/3-) and >100 for
      Ru(NH(3))(6)(3+/2+)), in marked contrast to previous studies that have found very
      slow electron transfer (ET) kinetics, with an interpretation that ET only occurs
      at step edges. Significantly, high spatial resolution electrochemical imaging
      with scanning electrochemical cell microscopy, on the highest quality
      mechanically cleaved HOPG, demonstrates definitively that the pristine basal
      surface supports fast ET, and that ET is not confined to step edges. However, the
      history of the HOPG surface strongly influences the electrochemical behavior.
      Thus, Fe(CN)(6)(4-/3-) shows markedly diminished ET kinetics with either extended
      exposure of the HOPG surface to the ambient environment or repeated CV
      measurements. In situ atomic force microscopy (AFM) reveals that the
      deterioration in apparent ET kinetics is coupled with the deposition of material
      on the HOPG electrode, while conducting-AFM highlights that, after cleaving, the
      local surface conductivity of HOPG deteriorates significantly with time. These
      observations and new insights are not only important for graphite, but have
      significant implications for electrochemistry at related carbon materials such as
      graphene and carbon nanotubes.

PMID- 23145937
TI  - Palladacycle-catalyzed reaction of bicyclic alkenes with terminal ynones:
      regiospecific synthesis of polysubstituted furans.
AB  - A new synthetic strategy to access polysubstituted furans regiospecifically has
      been developed using simple bicyclic alkenes and terminal ynones as starting
      materials with palladacycles as unique active catalysts. A rational mechanism has
      also been proposed. This reaction features mild reaction conditions, easily
      available starting materials and palladacycle catalysts, a wide substrate scope,
      and high regiospecificity.

PMID- 23145938
TI  - Structure and redox behavior of iron oxophlorin and role of electron transfer in
      the heme degradation process.
AB  - Iron-oxophlorin is an intermediate in heme degradation, and the metal oxidation
      number can alter spin, electron distribution, and the reactivity of the metal and
      the oxophlorin ring. The role of electron transfer in the structure and
      reactivity of [(Py)(2)Fe(III)(PO)] (PO is the oxophlorin trianion) in different
      redox states has been investigated using the B3LYP and OPBE methods with the 6
      31+G* and 6-311+G** basis sets. A computation study has shown that [(py)(2)
      Fe(III)(PO)] loses one electron from its a(2u) orbital. Thus the oxidized
      species, [(Py)(2)Fe(III)(PO(*))](+) (where PO(*) is the oxophlorin dianion
      radical), has an open-shell-singlet ground state with a d(xy)(2) d(xz)(2)
      a(2u)(1) d(yz)(1) electronic configuration with closely lying triplet and quintet
      states which are populated at ambient temperature. The aforementioned complex is
      highly reactive toward O(2). The reduced species [(Py)(2)Fe(II)(POH)] (where POH
      is the hydroxyheme) has the closed-shell-singlet ground state (pi(xz) pi(yz))(4)
      a(2u)(2) d(xy)(2) electronic configuration in which pyridines have a more pi
      accepting character and, thus, are tightly bound to iron. This reduced form is
      considerably less reactive toward O(2). The axial ligands effects (Im, t-BuNC)
      have also been studied in redox reactions of iron oxophlorin complexes. Complex
      [(Im)(2)Fe(III)(PO)] shows facile oxidation to form a cation radical and a
      reduction to form hydroxy while the [(t-BuNC)(2)Fe(II)(PO(*))] has high positive
      oxidation potential.

PMID- 23145939
TI  - Prevalence of level V metastasis in head and neck squamous cell carcinoma.
AB  - CONCLUSION: The results of this study accord with those of past reports about the
      prevalence of level V metastasis in head and neck squamous cell carcinoma (HNSCC)
      cases. Because of the low rate of level V metastasis, and from the viewpoint of
      standard postoperative radiotherapy, selective neck dissection without level V
      dissection may be possible in cases without clinical evidence of level V
      metastasis on both the ipsilateral and contralateral sides. In addition, degree
      of pathological differentiation and pN stage >N2b are suggested risk factors for
      level V metastasis. OBJECTIVES: The most frequent complication of any type of
      neck dissection in HNSCC cases with level V metastasis is shoulder dysfunction
      secondary to traction or ischemic injury to the spinal accessory nerve (SAN). The
      purpose of this study was to examine procedures to preserve the SAN and avoid
      level V dissection and shoulder dysfunction due to SAN injury. This study
      investigated the prevalence of level V metastasis and its associated risk factors
      at various primary sites in patients with HNSCC. METHODS: Clinical and
      pathological data were retrospectively reviewed for 162 patients with HNSCC,
      including those with clinically negative neck (cN0) and clinically positive neck
      (cN+) in whom level V neck dissection was performed. The prevalence of
      pathological metastasis to level V lymph nodes on both the ipsilateral and
      contralateral sides was investigated. Several potentially predictive risk factors
      for level V metastasis, such as age, sex, primary site, T stage, N stage, degree
      of pathological differentiation, and lymph node status of levels I-IV, were also
      evaluated. Statistical analysis was performed using Fisher's exact test. RESULTS:
      In total, 301 neck dissections (ipsilateral side, n = 162; contralateral side, n
      = 139) were performed in this study. The most common primary site was the oral
      cavity (n = 51), followed by the larynx (n = 48), hypopharynx (n = 39), and
      oropharynx (n = 24). On the ipsilateral side, the overall incidence of
      pathologically positive neck (pN+) was 63.6% (103/162). The overall prevalence of
      level V metastasis was 7.4% (12/162), 6.8% (11/162) on the ipsilateral side, and
      1.4% (2/139) on the contralateral side. Isolated level V metastasis and bilateral
      level V metastasis was observed in three patients and one patient, respectively.
      Metastasis to level V and other levels was observed in eight patients (8/96,
      8.3%), and level V involvement on the ipsilateral side alone was observed only in
      three patients (3/66, 4.5%). There were two cases in which level V was involved
      when the other levels were also involved (2/22, 9.1%), and there was no case in
      which the other levels were not involved on the contralateral side. A
      statistically significant association was found between level V metastasis and pN
      stage >N2b (p = 0.0035), degree of pathological differentiation (p = 0.0305) on
      the ipsilateral side, status of neck levels I-IV (p = 0.001), and the number of
      positive neck levels (p < 0.0001) on the contralateral side.

PMID- 23145940
TI  - Antithymocyte globulin induction therapy improves survival in lung
      transplantation for cystic fibrosis.
AB  - Cystic fibrosis (CF) is an inherited condition that leads to respiratory failure
      and is the third most common indication for adult bilateral lung transplantation
      (LuTX). In contrast to other lung diseases, the immune system of CF patients is
      up-regulated and we therefore hypothesized that these patients would benefit from
      induction therapy. In the current study, we investigated the impact of
      antithymocyte globulin (ATG) induction therapy in CF patients after LuTX. One
      hundred and forty six patients who underwent LuTX for CF at our centre between
      January 1999 and December 2010 were included in the study and retrospectively
      analysed. They were divided into two groups according to the immunosuppressive
      protocol: group-A (n = 103) with and group-B (n = 43) without induction therapy
      on top of the basic calcineurin inhibitor based triple immunosuppression with
      mycophenolate mofetil and steroids. Perioperative survival was significantly
      better in the ATG group, a benefit sustained for the entire follow-up. ATG
      induction resulted in a significantly lower incidence of acute rejections without
      an increase in infectious complications. Taken together, our results indicate
      that ATG induction therapy confers a significant survival benefit in CF patients
      undergoing LuTX and reduces rejection. We advocate the use of induction therapy
      in this patient cohort.

PMID- 23145941
TI  - Short communication: neutralizing antibodies in HIV-1-infected Brazilian
      individuals.
AB  - Tests for the detection of the humoral immune response to HIV-1 have to be
      standardized and established, demanding regional efforts. For this purpose the
      neutralizing antibody (NAb) assay for HIV-1 in TZM-bl cells was introduced in
      Brazil. Twenty plasma samples from HIV-1-infected individuals were assayed: 10
      progressors and 10 long-term nonprogressors. These were tested against eight env
      pseudotyped viruses (psVs) in the TZM-bl NAb assay and against HIV-1 strain
      HTLV/IIIB (HIV-1 IIIB) in primary lymphocytes. Forty-four percent of the samples
      showed neutralizing titers for psVs and 55% for HIV-1 IIIB. Plasma from
      progressors showed a broader neutralization and a higher potency. The
      introduction of these reference reagents encourages the participation of Brazil
      in future comparative assessments of anti-HIV-1 antibodies.

PMID- 23145942
TI  - Commentary on "biomineralization--an active or passive process?".

PMID- 23145943
TI  - Cerebral perfusion during cardiopulmonary bypass in children: correlations
      between near-infrared spectroscopy, temperature, lactate, pump flow, and blood
      pressure.
AB  - Near-infrared spectroscopy (NIRS) is a noninvasive modality to monitor regional
      brain oxygenation (rSO(2) ). In this study, we aimed to investigate the
      correlation between cerebral rSO(2)  and lactate, pump flow, hematocrit, pCO(2) ,
      and mean blood pressure (MBP) during cardiopulmonary bypass (CPB). Between March
      and September 2011, 50 pediatric patients who underwent congenital heart surgery
      were enrolled into the study. Ages ranged from 6 days to 168 months (median 14
      months). A NIRS sensor (Somanetics 5100B, Troy, MI, USA) was placed on the right
      forehead of patients. CPB period was divided into five stages: 1-at the beginning
      of CBP, 2-cooling at 32 degrees C, 3-at final hypothermic temperature, 4
      rewarming at 32 degrees C, 5-before weaning from CPB. Data collection included
      measurements of each parameter at five stages of CPB. Data were analyzed using
      multivariate analysis within groups and Spearman's correlation to test
      association between parameters. Lactate levels increased significantly from stage
      1 to stage 5 during CPB (P < 0.05). There was no significant correlation between
      cerebral rSO(2)  and MBPs, pump flows, hematocrit, or pCO(2)  during CPB.
      Cerebral rSO(2)  levels showed changes between the stages; there was a
      significant increase during cooling period, compared to stage 1 (P < 0.05).
      Significant changes during cooling stage did not happen for other parameters. At
      stage 3, there was a negative correlation between lactate level and MBP. At stage
      4, there was no significant change in cerebral rSO(2)  levels despite decreased
      MBP. At the warming stage, low MBPs, but normal rSO(2)  values, are observed
      despite increased pump flows. Increased rSO(2)  levels despite insignificant
      changes at other parameters during the cooling stage of CPB may show that optimal
      pump flow with adequate intravascular volume may provide effective cerebral
      perfusion even without changes in MBP. Considering normal rSO(2)  values during
      CPB in this study, it may be speculated that brain protection can be assessed by
      using NIRS and applying a standard bypass protocol.

PMID- 23145944
TI  - Dendrimeric bowties featuring hemispheric-selective decoration of ligands for
      microRNA-based therapy.
AB  - Dendrimers feature a defined number of terminal groups that may bind RNA or be
      functionalized with bioactive molecules. These competing uses of terminal groups
      may create an impasse if the requisite density of ligands depletes the number of
      terminal groups for binding sufficient RNA, or vice versa. A novel dendrimeric
      platform is needed that maintains high ligand density while retaining sufficient
      microRNA-binding terminal groups. Here we present a dendrimeric "bowtie"
      consisting of one-half devoted to microRNA binding and the other half to ligand
      presentation. We demonstrate its suitability as a transfection agent by
      delivering miR-126 to human vascular endothial cells (HUVECs) via polyarginine-
      and RGD-modified bowties and evaluating the downstream effects on proliferation
      and tube formation. Our findings indicate that the bowtie elicits desired
      responses and may possess superior delivery properties compared to nondecorated
      dendrimeric materials. The bowtie system thereby provides a new design model for
      developing dendrimeric delivery vehicles for RNAi therapeutics.

PMID- 23145945
TI  - Health status and socio-economic factors associated with health facility
      utilization in rural and urban areas in Zambia.
AB  - BACKGROUND: With regards to equity, the objective for health care systems is
      "equal access for equal needs". We examined associations of predisposing,
      enabling and need factors with health facility utilization in areas with high HIV
      prevalence and few people being aware of their HIV status. METHODS: The data is
      from a population-based survey among adults aged 15years or older conducted in
      2003. The current study is based on a subset of this data of adults 15-49 years
      with a valid HIV test result. A modified Health behaviour model guided our
      analytical approach. We report unadjusted and adjusted odds ratios and their 95%
      confidence intervals from logistic regression analyses. RESULTS: Totals of 1042
      males and 1547 females in urban areas, and 822 males and 1055 females in rural
      areas were included in the study. Overall, 53.1% of urban and 56.8% of rural
      respondents utilized health facilities past 12 months. In urban areas,
      significantly more females than males utilized health facilities (OR=1.4 (95% CI
      [1.1, 1.6]). Higher educational attainment (10+ years of schooling) was
      associated with utilization of health facilities in both urban (OR=1.7, 95% CI
      [1.3, 2.1]) and rural (OR=1.4, 95% CI [1.0, 2.0]) areas compared to respondents
      who attained up to 7 years of schooling. Respondents who self-rated their health
      status as very poor/ poor/fair were twice more likely to utilize health
      facilities compared to those who rated their health as good/excellent.
      Respondents who reported illnesses were about three times more likely to utilize
      health facilities compared to those who did not report the illnesses. In urban
      areas, respondents who had mental distress were 1.7 times more likely to utilize
      health facilities compare to those who had no mental distress. Compared to
      respondents who were HIV negative, respondents who were HIV positive were 1.3
      times more likely to utilize health facilities. CONCLUSION: The health care needs
      were the factors most strongly associated with health care seeking. After
      accounting for need differentials, health care seeking differed modestly by urban
      and rural residence, was somewhat skewed towards women, and increased
      substantially with socioeconomic position.

PMID- 23145947
TI  - Relationship between ABO genotype and A antigen expression on platelets.
AB  - BACKGROUND: Although platelets (PLTs) are known to express ABH antigens, the
      extent of expression is different on PLTs compared with red blood cells and the
      relationship between PLT ABH expression and genotype has not been thoroughly
      investigated. STUDY DESIGN AND METHODS: We measured blood group H and A antigens
      on PLTs from 100 normal volunteers using fluorescent-conjugated reagents and flow
      cytometry. Individuals were also genotyped at the ABO locus using a commercially
      available genotyping system. RESULTS: Expression of A and H antigen varied widely
      on PLTs from different individuals. Among group A and AB persons, H antigen
      expression was significantly greater than A antigen (p < 0.0001). The ratio of H
      to-A antigen expression varied more than 100-fold in a predictable fashion
      according to genotype with values lowest in A1/A1  < A1/O < A2/A2  < A2/O. H and
      A antigen expression was unaffected by secretor status. The proportion of PLTs
      with high A expression also varied directly according to genotype. CONCLUSIONS:
      Blood group A and H antigen expression on PLTs varies in a predictable fashion
      according to genotype. Flow cytometry and genotyping identify individuals who
      strongly express A antigens, a finding that may be relevant to clinical PLT
      transfusion across ABO barriers.

PMID- 23145948
TI  - Improved protocol for the synthesis of flexibly protected morpholino monomers
      from unprotected ribonucleosides.
AB  - An inexpensive and much improved protocol has been developed for the synthesis of
      protected morpholino monomers from unprotected ribonucleosides in high overall
      yield, using oxidative glycol cleavage and reductive amination strategy. Unlike
      the previous methods, the present strategy allows installing the exocyclic amine
      protections at a later stage, and thus avoids the use of expensive, or
      commercially unavailable, exocyclic amine-protected ribonucleosides as starting
      materials. To demonstrate the flexibility of the present method in choosing
      protecting groups, the monomers have been protected with several such groups of
      different deblocking properties at the exocyclic amine position.

PMID- 23145946
TI  - NS309 decreases rat detrusor smooth muscle membrane potential and phasic
      contractions by activating SK3 channels.
AB  - BACKGROUND AND PURPOSE: Overactive bladder (OAB) is often associated with
      abnormally increased detrusor smooth muscle (DSM) contractions. We used NS309, a
      selective and potent opener of the small or intermediate conductance Ca(2+) 
      activated K(+) (SK or IK, respectively) channels, to evaluate how SK/IK channel
      activation modulates DSM function. EXPERIMENTAL APPROACH: We employed single-cell
      RT-PCR, immunocytochemistry, whole cell patch-clamp in freshly isolated rat DSM
      cells and isometric tension recordings of isolated DSM strips to explore how the
      pharmacological activation of SK/IK channels with NS309 modulates DSM function.
      KEY RESULTS: We detected SK3 but not SK1, SK2 or IK channels expression at both
      mRNA and protein levels by RT-PCR and immunocytochemistry in DSM single cells.
      NS309 (10 MUM) significantly increased the whole cell SK currents and
      hyperpolarized DSM cell resting membrane potential. The NS309 hyperpolarizing
      effect was blocked by apamin, a selective SK channel inhibitor. NS309 inhibited
      the spontaneous phasic contraction amplitude, force, frequency, duration and tone
      of isolated DSM strips in a concentration-dependent manner. The inhibitory effect
      of NS309 on spontaneous phasic contractions was blocked by apamin but not by TRAM
      34, indicating no functional role of the IK channels in rat DSM. NS309 also
      significantly inhibited the pharmacologically and electrical field stimulation
      induced DSM contractions. CONCLUSIONS AND IMPLICATIONS: Our data reveal that SK3
      channel is the main SK/IK subtype in rat DSM. Pharmacological activation of SK3
      channels with NS309 decreases rat DSM cell excitability and contractility,
      suggesting that SK3 channels might be potential therapeutic targets to control
      OAB associated with detrusor overactivity.

PMID- 23145949
TI  - Synthesis and antimicrobial evaluation of novel pyrazolones and pyrazolone
      nucleosides.
AB  - The synthesis of a novel series of 4-arylhydrazono-5-methyl-1,2-dihydropyrazol-3
      ones 4a-h, and their N (2)-alkyl and acyclo, glucopyranosyl, and ribofuranosyl
      derivatives is described. K(2)CO(3) catalyzed alkylation of 4a-h with allyl
      bromide, propargyl bromide, 4-bromobutyl acetate, 2-acetoxyethoxymethyl bromide,
      and 2,3,4,6-tetra-O-acetyl-alpha-D-glucopyranosyl bromide proceeded selectively
      at the N (2)-position of the pyrazolinone ring. Glycosylation of 4a with 1,2,3,5
      tetra-O-acetyl-beta-D-ribofuranose under Vorbruggen glycosylation conditions gave
      the corresponding N (2)-4-arylhydrazonopyrazolone ribofuranoside 9a in good
      yield. Conventional deprotection of the acetyl protected nucleosides furnished
      the corresponding 4-arylhydrazonopyrazolone nucleosides in good yields. Selected
      numbers of the newly synthesized compounds were screened for antimicrobial
      activity. Compounds 4b, 12a, and 14 d showed moderate activities against
      Aspergillus flavus, Penicillium sp., and Escherichia coli.

PMID- 23145950
TI  - Is there any interaction between telomeric DNA structures, G-quadruplex and I
      motif, with saffron active metabolites?
AB  - Telomeric DNA contains some unique secondary structures, such as G-quadruplex and
      I-motif. These structures may be stabilized or changed by binding to specific
      proteins or small molecules. Herein, we report the in vitro effect of crocin,
      crocetin, picrocrocin, and safranal on these structures. Circular dichroism (CD)
      data indicate that crocetin has higher affinity for these structures. Safranal
      and crocin induce little change in the I-motif and G-quadruplex, respectively.
      The molecular docking confirms the experimental data and indicates the minor
      groove binding of ligands with G-quadruplex. The possibility for application of
      these ligands as sequence-specific drugs should be further investigated.

PMID- 23145951
TI  - Synthesis, DNA binding, and photonuclease activity of new tetraaza macrocyclic
      constrained isoxazole rings as subunit in metal complexes.
AB  - The DNA-binding and photonuclease activity of newly synthesized tetra
      azamacrocyclic ligand L (C(32)H(32)N(8)O(4)) and its complexes of type [MLCl(2)]
      and [ML]Cl(2) (where M = Co(II), Fe(II) and Cu(II); L = N,N'-[3-(4-{5-[(2-amino
      ethylamino)-methyl]-isoxazol-3yl}-phenyl)-isoxazol-5-yl methyl-ethane-1,2
      diamine] are specified. An octahedral geometry has been proposed for Fe(II) and
      Co(II) complexes, while the Cu(II) complex has a square planar environment. The
      absorption spectral results indicate that the complexes bind with the base pairs
      of DNA, with an intrinsic binding constant K(b) of Fe(II), Co(II), and Cu(II)
      complexes found to be 3.2 * 10(4) M(-1), 5.3 * 10(4) M(-1), and 4.2 * 10(4) M(
      1), respectively, in 5 mM Tris-HCl/50 mM NaCl buffer at pH 7.2. The large
      enhancement in the relative viscosity of DNA on binding to the complexes supports
      the proposed DNA binding modes. The viscosity and thermal denaturation studies
      sustain the effective intercalation with DNA. The DNA photocleavage studies
      demonstrated that compounds exhibit significant photonuclease activity by a
      concentration dependent on singlet oxygen mediated mechanism.

PMID- 23145953
TI  - Prisons: the psychiatric institution of last resort?
AB  - The World Health Organization declared in 1948 that the enjoyment of the highest
      individual attainment of health for any person is a fundamental human right.
      Australia, the U.K. and the United States all legally ratified this declaration
      as becoming signatories to their founding treatise with the United Nations.
      Despite this, there are many conspicuous examples of inequities of public health
      as found within these nations. One of the more disparate and outrageous examples
      of inequities in public health has been an insidious trend towards criminalizing
      mental illness, and the largely unjust treatment of many mentally ill persons.
      This change has resulted in untold numbers of mentally ill persons being over
      represented within the criminal justice system, experiencing higher morbidity, co
      morbidity and mortality rates, and having difficulty in surviving in a society
      frequently dealing with their illness in a persecutory manner. Questions must be
      raised: that although over the passage of time medical science and technology has
      changed, but has western societies' attitudes to health equity kept pace?

PMID- 23145954
TI  - Morphology and morphometry of fetal liver at 16-26 weeks of gestation by magnetic
      resonance imaging: Comparison with embryonic liver at Carnegie stage 23.
AB  - AIM: Normal liver growth was described morphologically and morphometrically using
      magnetic resonance imaging (MRI) data of human fetuses, and compared with
      embryonic liver to establish a normal reference chart for clinical use. METHODS:
      MRI images from 21 fetuses at 16-26 weeks of gestation and eight embryos at
      Carnegie stage (CS)23 were investigated in the present study. Using the image
      data, the morphology of the liver as well as its adjacent organs was extracted
      and reconstructed three-dimensionally. Morphometry of fetal liver growth was
      performed using simple regression analysis. RESULTS: The fundamental morphology
      was similar in all cases of the fetal livers examined. The liver tended to grow
      along the transversal axis. The four lobes were clearly recognizable in the fetal
      liver but not in the embryonic liver. The length of the liver along the three
      axes, liver volume and four lobes correlated with the bodyweight (BW). The
      morphogenesis of the fetal liver on the dorsal and caudal sides was affected by
      the growth of the abdominal organs, such as the stomach, duodenum and spleen, and
      retroperitoneal organs, such as the right adrenal gland and right kidney. The
      main blood vessels such as inferior vena cava, portal vein and umbilical vein
      made a groove on the surface of the liver. Morphology of the fetal liver was
      different from that of the embryonic liver at CS23. CONCLUSION: The present data
      will be useful for evaluating the development of the fetal liver and the adjacent
      organs that affect its morphology.

PMID- 23145952
TI  - A randomized trial of tigecycline versus ampicillin-sulbactam or amoxicillin
      clavulanate for the treatment of complicated skin and skin structure infections.
AB  - BACKGROUND: Complicated skin and skin structure infections (cSSSIs) frequently
      result in hospitalization with significant morbidity and mortality. METHODS: In
      this phase 3b/4 parallel, randomized, open-label, comparative study, 531 subjects
      with cSSSI received tigecycline (100 mg initial dose, then 50 mg intravenously
      every 12 hrs) or ampicillin-sulbactam 1.5-3 g IV every 6 hrs or amoxicillin
      clavulanate 1.2 g IV every 6-8 hrs. Vancomycin could be added at the discretion
      of the investigator to the comparator arm if methicillin-resistant Staphylococcus
      aureus (MRSA) was confirmed or suspected within 72 hrs of enrollment. The primary
      endpoint was clinical response in the clinically evaluable (CE) population at the
      test-of-cure (TOC) visit. Microbiologic response and safety were also assessed.
      The modified intent-to-treat (mITT) population comprised 531 subjects
      (tigecycline, n = 268; comparator, n = 263) and 405 were clinically evaluable
      (tigecycline, n = 209; comparator, n = 196). RESULTS: In the CE population,
      162/209 (77.5%) tigecycline-treated subjects and 152/196 (77.6%) comparator
      treated subjects were clinically cured (difference 0.0; 95% confidence interval
      [CI]: -8.7, 8.6). The eradication rates at the subject level for the
      microbiologically evaluable (ME) population were 79.2% in the tigecycline
      treatment group and 76.8% in the comparator treatment group (difference 2.4; 95%
      CI: -9.6, 14.4) at the TOC assessment. Nausea, vomiting, and diarrhea rates were
      higher in the tigecycline group. CONCLUSIONS: Tigecycline was generally safe and
      effective in the treatment of cSSSIs. TRIAL REGISTRATION: ClinicalTrials.gov
      NCT00368537.

PMID- 23145955
TI  - Poultry rearing and slaughtering practices in rural Egypt: an exploration of risk
      factors for H5N1 virus human transmission.
AB  - BACKGROUND: Highly pathogenic avian influenza (H5N1) virus continues to cause
      infections in Egypt. This study describes the practices associated with raising
      and slaughtering household poultry to identify risk factors for H5N1 infection
      and reasons for non-compliance with preventive measures. METHODS: An
      investigation was conducted of 56 households with household flocks (19 households
      with human H5N1 cases, 19 with poultry H5N1 cases, and 18 with no reported
      poultry or human H5N1 cases). Data were collected via structured observations and
      in-depth interviews. RESULTS: Half of the households kept at least some free
      range poultry and mixed at least some different species of poultry as it was
      considered beneficial for the poultry. Feeding and cleaning practices exposed
      children to contact with poultry; slaughtering contaminated homes; use of
      personal protective barriers was not a norm; waste management exposed the
      communities to slaughtering waste and dead chickens; and reporting of sick and
      dead poultry was not a practice. Only minor changes in poultry-handling took
      place following H5N1 virus outbreaks. DISCUSSION: H5N1 virus prevention in Egypt
      represents both an epidemiological and socio-cultural challenge. Traditional
      poultry-rearing practices that likely increase exposures to H5N1-infected poultry
      are common throughout Egypt. Despite education campaigns following sporadic H5N1
      outbreaks, no differences in these practices could be detected between households
      with previous H5N1 human or poultry cases and those households with any previous
      experience with H5N1. Development of H5N1 infection-related education campaign
      strategies should focus on perceptions underlying traditional practices in order
      to tailor public awareness messages that are meaningful for communities.

PMID- 23145956
TI  - Comment on "Development of a measurement technique for ion distribution in an
      extended nanochannel by super-resolution-laser-induced fluorescence".

PMID- 23145957
TI  - Coitus to expedite the onset of labour: a randomised trial.
AB  - OBJECTIVE: To evaluate the effect of suggesting coitus as a safe and effective
      means to expedite labour on pregnancy duration and requirement for labour
      induction. DESIGN: A randomised trial. SETTING: Antenatal clinic in a university
      hospital in Malaysia. POPULATION: Women from 35 weeks of gestation with an
      uncomplicated singleton pregnancy. METHODS: The advise-coitus arm was counselled
      that coitus at term is a safe, natural and effective means to initiate labour and
      to avoid labour induction. The control arm was told coitus was safe. Both arms
      were asked to record coital activity. MAIN OUTCOME MEASURES: Pregnancy duration
      and labour induction. RESULTS: The intervention to delivery interval (mean +/-
      SD) was 3.2 +/- 1.4 versus 3.3 +/- 1.3 weeks (P = 0.417), with a gestational age
      at delivery of 39.4 +/- 1.2 versus 39.5 +/- 1.2 weeks (P = 0.112), and with
      labour induction rates of 126/574 (22.0%) versus 120/576 (20.8%) (P = 0.666) for
      the advise-coitus and control arms, respectively, with no statistical difference
      between the groups. Coitus prior to delivery was more often reported in the
      advise-coitus arm compared with the control arm: 481/574 (85.3%) versus 458/576
      (79.9%) (RR 1.5, 95% CI 1.1-2.0, P = 0.019). Also, the median (interquartile
      range) reported number of coital acts of 3 (2-5) versus 2 (1-4) (P = 0.006) was
      higher for the advise-coitus arm. Other pregnancy and neonatal outcomes did not
      differ between the groups. CONCLUSIONS: Labour onset and labour induction did not
      differ in the advise-coitus arm.

PMID- 23145958
TI  - An investigation into the altered binding mode of green tea polyphenols with
      human serum albumin on complexation with copper.
AB  - Green tea is rich in several polyphenols, such as (-)-epicatechin-3-gallate
      (ECG), (-)-epigallocatechin (EGC), and (-)-epigallocatechin-3-gallate (EGCG). The
      biological importance of these polyphenols led us to study the major polyphenol
      EGCG with human serum albumin (HSA) in an earlier study. In this report, we have
      compared the binding of ECG, EGC, and EGCG and the Cu(II) complexes of EGCG and
      ECG with HSA. We observe that the gallate moiety of the polyphenols plays a
      crucial role in determining the mode of interaction with HSA. The binding
      constants obtained for the different systems are 5.86 +/- 0.72 * 104 M-1 (K ECG
      HSA), 4.22 +/- 0.15 * 104 M-1 (K ECG-Cu(II)-HSA), and 9.51 +/- 0.31 * 104 M-1 (K
      EGCG-Cu(II)-HSA) at 293 K. Thermodynamic parameters thus obtained suggest that
      apart from an initial hydrophobic association, van der Waals interactions and
      hydrogen bonding are the major interactions which held together the polyphenols
      and HSA. However, thermodynamic parameters obtained from the interactions of the
      copper complexes with HSA are indicative of the involvement of the hydrophobic
      forces. Circular dichroism and the Fourier transform infrared spectroscopic
      measurements reveal changes in alpha-helical content of HSA after binding with
      the ligands. Data obtained by fluorescence spectroscopy, displacement experiments
      along with the docking studies suggested that the ligands bind to the residues
      located in site 1 (subdomains IIA), whereas EGC, that lacks the gallate moiety,
      binds to the other hydrophobic site 2 (subdomain IIIA) of the protein.

PMID- 23145960
TI  - Enantioselective synthesis of spiroacetals via silver(I)-promoted alkylation of
      hemiacetals: total synthesis of cephalosporolides E and F.
AB  - A silver(I)-promoted intramolecular hemiacetal alkylation has been developed that
      converts readily available keto-chlorodiols into functionalized spiroacetals
      containing 5,5-, 5,6-, and 5,7-membered ring systems. The efficiency of this
      process is demonstrated in a concise total synthesis of the fungal metabolites
      cephalosporolides E and F.

PMID- 23145959
TI  - Tuning nanostructure dimensions with supramolecular twisting.
AB  - Peptide amphiphiles are molecules containing a peptide segment covalently bonded
      to a hydrophobic tail and are known to self-assemble in water into supramolecular
      nanostructures with shape diversity ranging from spheres to cylinders, twisted
      ribbons, belts, and tubes. Understanding the self-assembly mechanisms to control
      dimensions and shapes of the nanostructures remains a grand challenge. We report
      here on a systematic study of peptide amphiphiles containing valine-glutamic acid
      dimeric repeats known to promote self-assembly into belt-like flat assemblies. We
      find that the lateral growth of the assemblies can be controlled in the range of
      100 nm down to 10 nm as the number of dimeric repeats is increased from two to
      six. Using circular dichroism, the degree of beta-sheet twisting within the
      supramolecular assemblies was found to be directly proportional to the number of
      dimeric repeats in the PA molecule. Interestingly, as twisting increased, a
      threshold is reached where cylinders rather than flat assemblies become the
      dominant morphology. We also show that in the belt regime, the width of the
      nanostructures can be decreased by raising the pH to increase charge density and
      therefore electrostatic repulsion among glutamic acid residues. The control of
      size and shape of these nanostructures should affect their functions in
      biological signaling and drug delivery.

PMID- 23145961
TI  - Dysregulation of REST-regulated coding and non-coding RNAs in a cellular model of
      Huntington's disease.
AB  - Huntingtin (Htt) protein interacts with many transcriptional regulators, with
      widespread disruption to the transcriptome in Huntington's disease (HD) brought
      about by altered interactions with the mutant Htt (muHtt) protein. Repressor
      Element-1 Silencing Transcription Factor (REST) is a repressor whose association
      with Htt in the cytoplasm is disrupted in HD, leading to increased nuclear REST
      and concomitant repression of several neuronal-specific genes, including brain
      derived neurotrophic factor (Bdnf). Here, we explored a wide set of HD
      dysregulated genes to identify direct REST targets whose expression is altered in
      a cellular model of HD but that can be rescued by knock-down of REST activity. We
      found many direct REST target genes encoding proteins important for nervous
      system development, including a cohort involved in synaptic transmission, at
      least two of which can be rescued at the protein level by REST knock-down. We
      also identified several microRNAs (miRNAs) whose aberrant repression is directly
      mediated by REST, including miR-137, which has not previously been shown to be a
      direct REST target in mouse. These data provide evidence of the contribution of
      inappropriate REST-mediated transcriptional repression to the widespread changes
      in coding and non-coding gene expression in a cellular model of HD that may
      affect normal neuronal function and survival.

PMID- 23145962
TI  - Pharmacokinetics and selected pharmacodynamic effects of tramadol following
      intravenous administration to the horse.
AB  - REASONS FOR PERFORMING STUDY: Both the potential analgesic effect and the
      conflicting reports describing tramadol disposition in the horse warrant further
      study of the pharmacokinetics of tramadol in this species. OBJECTIVES: To
      describe the pharmacokinetics of tramadol and its metabolites, O
      desmethyltramadol and N-desmethyltramadol, following i.v. administration of 3
      doses to the horse. METHODS: Nine adult horses received a single i.v. dose of
      0.5, 1.5 and 3 mg/kg bwt tramadol. Blood samples were collected prior to and at
      various times up to 72 h post administration. Plasma samples were analysed using
      liquid chromatography-mass spectrometry and data analysed using noncompartmental
      analysis. Chin-to-ground distance, heart rate and rhythm, step count and
      gastrointestinal activity were also assessed. RESULTS: Maximal measured plasma
      tramadol concentrations were 454 +/- 101.6, 1086.7 +/- 330.7 and 1697.9 +/- 406.1
      ng/ml for 0.5, 1.5 and 3 mg/kg bwt, respectively. Depending on the dose
      administered, the tramadol clearance, volume of distribution and half-life ranged
      from 24.6 to 25.0 ml/min/kg, 2.66 to 3.33 l/kg and 2.17 to 3.05 h, respectively.
      Following administration of 0.5, 1.5 and 3 mg/kg bwt tramadol, the maximal
      measured plasma concentrations of the active metabolite, O-desmethyltramadol,
      were 3.9 +/- 1.9, 9.6 +/- 4.8 and 12.9 +/- 5.2 ng/ml, respectively. Muscle
      fasiculations and tremors were seen following administration of the 2 high doses.
      No significant changes in chin-to-ground distance, heart rate and rhythm, step
      count and gastrointestinal activity were observed. CONCLUSIONS AND POTENTIAL
      RELEVANCE: This study confirms and extends previous studies describing the
      pharmacokinetics of tramadol following i.v. administration to the horse. Plasma
      tramadol concentrations exceeded those necessary for analgesia in human patients;
      however, further studies are necessary to determine plasma concentrations of
      tramadol necessary for analgesic efficacy in the horse. These results support
      further investigation of the analgesic efficacy of tramadol in the horse.

PMID- 23145963
TI  - Probing high-pressure phase transitions in Ti-based perovskite-type
      ferroelectrics using visible resonance Raman spectroscopy.
AB  - We report unprecedented dramatic changes in the 647.1 nm Raman signal of
      PbZr(0.6)Ti(0.4)O(3) occurring in the same pressure ranges as the critical
      pressures of the antiferrodistortive and ferroelectric-paraelectric phase
      transitions. This huge decrease in intensity of both the Raman modes and the
      background, observed for both pressure transmitting media used (glycerol or 4:1
      methanol ethanol mixture), is shown to originate from the two-step loss of a
      resonance Raman effect and the concomitant fluorescence. Changes in the local
      titanium environment (first with the onset of octahedral tilting and then with
      the removal of polar cation displacements) alter the electronic band structure
      and modify the resonance conditions. Furthermore, the optimal resonance
      conditions are found to be particularly narrow, as shown by the fluorescence
      spectrum of PbZr(0.6)Ti(0.4)O(3) at atmospheric pressure characterized by the
      presence of a very well-defined sharp peak (fwhm = 8 nm) centered around 647.1
      nm. These results thus demonstrate that visible resonance Raman spectroscopy can
      be used as a quick and efficient technique for probing phase transitions in
      PbZr(1-x)Ti(x)O(3) (PZT) and other technologically important perovskite-type
      materials such as PMN-xPT, PZN-xPT relaxors, lead free piezoelectrics, and
      ferroelectric nanopowders. This technique appears also a good alternative to UV
      Raman spectroscopy for probing the polar order at the nanoscale in ultrathinfilms
      and superlattices.

PMID- 23145965
TI  - Solid-phase synthesis of trisubstituted benzo[1,4]-diazepin-5-one derivatives.
AB  - Solid-phase synthesis of 3,4-dihydro-benzo[e][1,4]diazepin-5-ones with three
      diversity positions is described. Various primary amines were used as the
      starting material and immobilized on the polystyrene resin equipped with
      different acid-labile linkers. Polymer-supported amines were converted to alpha
      aminoketones with the use of their sulfonylation with the 4
      nitrobenzensulfonylchoride (4-Nos-Cl) and subsequent alkylation with alpha
      bromoketones. After the cleavage of the 4-Nos group, the corresponding alpha
      aminoketones were acylated with various o-nitrobenzoic acids. Reduction of the
      nitro group followed by spontaneous on-resin ring closure gave the target
      immobilized benzodiazepines. After acid-mediated cleavage the products were
      obtained in very good crude purity and satisfactory yields, which makes the
      developed method applicable for simple library synthesis of the corresponding
      derivatives in a combinatorial fashion.

PMID- 23145964
TI  - DNA damage induces nucleoid compaction via the Mre11-Rad50 complex in the
      archaeon Haloferax volcanii.
AB  - In prokaryotes the genome is organized in a dynamic structure called the
      nucleoid, which is embedded in the cytoplasm. We show here that in the archaeon
      Haloferax volcanii, compaction and reorganization of the nucleoid is induced by
      stresses that damage the genome or interfere with its replication. The fraction
      of cells exhibiting nucleoid compaction was proportional to the dose of the DNA
      damaging agent, and results obtained in cells defective for nucleotide excision
      repair suggest that breakage of DNA strands triggers reorganization of the
      nucleoid. We observed that compaction depends on the Mre11-Rad50 complex,
      suggesting a link to DNA double-strand break repair. However, compaction was
      observed in a radA mutant, indicating that the role of Mre11-Rad50 in nucleoid
      reorganisation is independent of homologous recombination. We therefore propose
      that nucleoid compaction is part of a DNA damage response that accelerates cell
      recovery by helping DNA repair proteins to locate their targets, and facilitating
      the search for intact DNA sequences during homologous recombination.

PMID- 23145966
TI  - Continuous glucose monitoring: a valuable monitoring tool for management of
      hypoglycemia during chemotherapy for acute lymphoblastic leukemia.
AB  - BACKGROUND: Acute lymphoblastic leukemia (ALL) maintenance therapy (MT) has been
      occasionally associated with symptomatic hypoglycemia (SH), attributed to purine
      analog (mercaptopurine [6-MP]). This hypoglycemia has been hypothesized to affect
      substrate utilization of gluconeogenic precursor alanine in the liver. CASE
      REPORT: An overweight 5-year-old boy with ALL was evaluated for SH (lethargy and
      vomiting) that occurred 8-10 h after fasting while receiving daily 6-MP.
      Hypoglycemic episodes (>20 episodes per month) occurred predominantly around
      midmorning but not during the 5-day dexamethasone pulse. The adrenocorticotropic
      hormone test yielded a normal cortisol response, which ruled out pituitary
      adrenal suppression. A 12-h overnight fasting glucose was 49 mg/dL, with
      suppressed insulin response <2 IU/mL, low C-peptide of 0.5 ng/mL, high insulin
      like growth factor-binding protein >160 ng/mL, high free fatty acid of 2.64
      mmol/L, and negative glucagon stimulation test (change in blood glucose [BG] <5
      mg/dL). These results ruled out hyperinsulinism. The patient was placed on
      cornstarch therapy 5 h prior to dosing with 6-MP. This treatment reduced the SH
      events to fewer than two episodes per month. To study the efficacy of cornstarch,
      the patient was fitted with the iProTM professional continuous glucose monitoring
      system (CGMS) (Medtronic MiniMed, Northridge, CA) with a preset low alarm at 70
      mg/dL, which was worn for a period of 5 days while the patient was on cornstarch.
      With 1,000 sensor reading the BG range was 65-158 mg/dL, and the percentage mean
      absolute difference between sensor and finger-stick BG readings (the parent
      monitored his BG four times a day) was 9.4%. There were no hypoglycemic episodes
      detected by the CGMS while the patient was on cornstarch. After the cessation of
      chemotherapy, a 15-h fasting study was performed, and the CGMS was placed.
      Results showed resolution of hypoglycemia. CONCLUSIONS: The CGMS helped us devise
      an effective management plan for our patient. CGMS proved useful as an adjunct to
      characterize the pattern of hypoglycemia and to validate the benefit of
      cornstarch in hypoglycemia associated with 6-MP treatment of ALL.

PMID- 23145967
TI  - Jacques Lacan's theory of the subject as real, symbolic and imaginary: how can
      Lacanian theory be of help to mental health nursing practice?
AB  - This paper presents an outline of Lacan's theory of the human subject, in
      particular focusing on Lacan's concepts of the real, symbolic and imaginary
      registers, and how an understanding of these can inform change and practice in
      mental health nursing. Mental health nursing is under pressure to define itself
      as a practice distinct from other professions in the field, and to respond in new
      ways to promoting mental health to the individual and a wider public. Lacan's
      theory of the subject is of particular relevance to mental health nurses working
      with mental distress but has received little attention in mental health nursing
      literature. Six implications for practice are outlined in terms of: against
      normalization, the importance of the function of the symptom, what cannot be
      known, meaning as ever-changing, against empathy and against holistic ideas of
      the self.

PMID- 23145968
TI  - Cation-pi interaction: its role and relevance in chemistry, biology, and material
      science.

PMID- 23145969
TI  - Vestibular abnormality in patients with Meniere's disease and migrainous vertigo.
AB  - CONCLUSION: Vestibular abnormality was found in 84% of patients with Meniere's
      disease (MD) and 66% of those with migrainous vertigo (MV), even in the
      interictal period. Although MV does not have proven pathology like endolymphatic
      hydrops of MD, MV had high vestibular abnormality, suggesting that comorbid
      vestibular abnormality can be a cause of vertigo and needs to be pursued.
      OBJECTIVES: MD and MV are common disorders causing recurrent vertigo. We
      determined the vestibular abnormality rates using vestibular tests with objective
      measurements. METHODS: Results of caloric, head-shaking nystagmus (HSN), and
      vibration-induced nystagmus (VIN) tests were analyzed in 45 patients with MD and
      76 with MV. RESULTS: The abnormal rates in MD were significantly higher than
      those in MV. Of 45 MD patients, 21 (47%), 32 (71%), and 24 (53%) exhibited
      abnormal caloric, HSN, and VIN results, respectively. Fourteen (31%) MD patients
      had migraine associated with vertigo, but the association was not accompanied by
      high rates of abnormal results in the tests. Of 76 MV patients, 19 (25%), 38
      (50%), and 24 (32%) exhibited abnormal caloric, HSN, and VIN results,
      respectively. Overall, 84% of patients with MD and 66% with MV exhibited abnormal
      results on at least one test. Abnormal rates were highest in HSN, followed by VIN
      and the caloric test.

PMID- 23145970
TI  - Participant experiences of mindfulness-based childbirth education: a qualitative
      study.
AB  - BACKGROUND: Childbirth is an important transitional life event, but one in which
      many women are dissatisfied stemming in part from a sense that labour is
      something that happens to them rather than with them. Promoting maternal
      satisfaction with childbirth means equipping women with communication and
      decision making skills that will enhance their ability to feel involved in their
      labour. Additionally, traditional antenatal education does not necessarily
      prepare expectant mothers and their birth support partner adequately for birth.
      Mindfulness-based interventions appear to hold promise in addressing these
      issues. Mindfulness-based Child Birth Education (MBCE) was a pilot intervention
      combining skills-based antenatal education and Mindfulness Based Stress
      Reduction. Participant experiences of MBCE, both of expectant mothers and their
      birth support partners are the focus of this article. METHODS: A generic
      qualitative approach was utilised for this study. Pregnant women between 18 and
      28 weeks gestation, over 18 years of age, nulliparous with singleton pregnancies
      and not taking medication for a diagnosed mental illness or taking illicit drugs
      were eligible to undertake the MBCE program which was run in a metropolitan city
      in Australia. Focus groups with 12 mothers and seven birth support partners were
      undertaken approximately four months after the completion of MBCE. Audio
      recordings of the groups were transcribed verbatim and analysed thematically
      using the method of constant comparison by all four authors independently and
      consensus on analysis and interpretation arrived at through team meetings.
      RESULTS: A sense of both 'empowerment' and 'community' were the essences of the
      experiences of MBCE both for mothers and their birth support partner and
      permeated the themes of 'awakening my existing potential' and 'being in a
      community of like-minded parents'. Participants suggested that mindfulness
      techniques learned during MBCE facilitated their sense of control during birth,
      and the content and pedagogical approach of MBCE enabled them to be involved in
      decision making during the birth. The pedagogical approach also fostered a sense
      of community among participants which extended into the postnatal period.
      CONCLUSIONS: MBCE has the potential to empower women to become active
      participants in the birthing process, thus addressing common concerns regarding
      lack of control and satisfaction with labour and facilitate peer support into the
      postnatal period. Further education of health professionals may be needed to
      ensure that they respond positively to those women and birth support partners who
      remain active in decision making during birth.

PMID- 23145971
TI  - The effect of blood transfusion on cerebral hemodynamics in preterm infants.
AB  - BACKGROUND: Anemia of prematurity commonly occurs in infants with very low birth
      weight; blood transfusion is an important treatment. However, there is no clear
      evidence to support the criteria currently widely used, based on blood hemoglobin
      (bHb) and hematocrit indices. Previous studies showed that overtransfusion or a
      low threshold for transfusion could induce complications or neurologic sequelae,
      respectively. We hypothesized that a cerebral hemodynamic index may provide an
      appropriate criterion for determining the need for transfusion in anemic preterm
      infants. STUDY DESIGN AND METHODS: We used near-infrared time-resolved
      spectroscopy to measure cerebral hemoglobin oxygen saturation (ScO2 ) and
      cerebral blood volume (CBV) before and after transfusion in 19 infants (24
      measurements) with anemia of prematurity. The median gestational age was 27 weeks
      0 days, median birth weight was 751 g, and median postconceptual age at
      transfusion was 30 weeks 4 days. RESULTS: bHb levels before and after transfusion
      (mean +/- SD) were 9.3 +/- 1.4 and 13.7 +/- 1.3 g/dL, respectively. After
      transfusion, CBV significantly decreased from 2.63 +/- 0.60 to 2.13 +/- 0.26
      mL/100 g of brain, and ScO2 significantly increased from 72.8 +/- 4.3% to 74.7 +/
      4.2%. CONCLUSION: After transfusion, CBV changes were significantly greater with
      low compared to high pretransfusion Hb levels. This reflected the physiologic
      response to severe anemia in premature infants, which is to increase CBV and
      decrease ScO2 . Therefore, CBV and ScO2 may be useful markers for determining the
      need for transfusion in very-low-birth-weight infants.

PMID- 23145972
TI  - The impact of primary healthcare in reducing inequalities in child health
      outcomes, Bogota-Colombia: an ecological analysis.
AB  - BACKGROUND: Colombia is one of the countries with the widest levels of
      socioeconomic and health inequalities. Bogota, its capital, faces serious
      problems of poverty, social disparities and access to health services. A Primary
      Health Care (PHC) strategy was implemented in 2004 to improve health care and to
      address the social determinants of such inequalities. This study aimed to
      evaluate the contribution of the PHC strategy to reducing inequalities in child
      health outcomes in Bogota. METHODS: An ecological analysis with localities as the
      unit of analysis was carried out. The variable used to capture the socioeconomic
      status and living standards was the Quality of Life Index (QLI). Concentration
      curves and concentration indices for four child health outcomes (infant mortality
      rate (IMR), under-5 mortality rate, prevalence of acute malnutrition in children
      under-5, and vaccination coverage for diphtheria, pertussis and tetanus) were
      calculated to measure socioeconomic inequality. Two periods were used to describe
      possible changes in the magnitude of the inequalities related with the PHC
      implementation (2003 year before - 2007 year after implementation). The
      contribution of the PHC intervention was computed by a decomposition analysis
      carried out on data from 2007. RESULTS: In both 2003 and 2007, concentration
      curves and indexes of IMR, under-5 mortality rate and acute malnutrition showed
      inequalities to the disadvantage of localities with lower QLI. Diphtheria,
      pertussis and tetanus (DPT) vaccinations were more prevalent among localities
      with higher QLI in 2003 but were higher in localities with lower QLI in 2007. The
      variation of the concentration index between 2003 and 2007 indicated reductions
      in inequality for all of the indicators in the period after the PHC
      implementation. In 2007, PHC was associated with a reduction in the effect of the
      inequality that affected disadvantaged localities in under-5 mortality (24%), IMR
      (19%) and acute malnutrition (7%). PHC also contributed approximately 20% to
      inequality in DPT coverage, favoring the poorer localities. CONCLUSION: The PHC
      strategy developed in Bogota appears to be contributing to reductions of the
      inequality associated with socioeconomic and living conditions in child health
      outcomes.

PMID- 23145973
TI  - Effect of fluoride on root resorption following heavy and light orthodontic force
      application for 4 weeks and 12 weeks of retention.
AB  - OBJECTIVE: To evaluate the null hypothesis that fluoride intake via drinking
      water has no effect on orthodontic root resorption in humans after orthodontic
      force application for 4 weeks and 12 weeks of retention. MATERIALS AND METHODS:
      Forty-eight patients who required maxillary premolar extractions as part of their
      orthodontic treatment were selected from two cities in Turkey. These cities had a
      high and low fluoride concentration in public water of >=2 pm and <=0.05 pm,
      respectively. The patients were randomly separated into four groups of 12 each:
      group 1HH, high fluoride (>=2 ppm) and heavy force (225 g); group 2LH, low
      fluoride (<=0.05 ppm) and heavy force; group 3HL, high fluoride and light force
      (25 g); and group 4LL, low fluoride and light force. Light or heavy buccal
      tipping force was applied on the upper first premolars for 28 days. At day 28,
      the left premolars were extracted (positive control side); the right premolars
      (experimental side) were extracted after 12 weeks of retention. The samples were
      analyzed with microcomputed tomography. RESULTS: On the positive control side,
      under heavy force application, the high fluoride groups exhibited less root
      resorption (P  =  .015). On the experimental side, it was found that fluoride
      reduced the total volume of root resorption craters; however, this effect was not
      statistically significant (P  =  .237). Moreover, the results revealed that under
      heavy force application experimental teeth exhibited more root resorption than
      positive control groups. CONCLUSION: The null hypothesis could not be rejected.
      High fluoride intake from public water did not have a beneficial effect on the
      severity of root resorption after a 4-week orthodontic force application and 12
      weeks of passive retention.

PMID- 23145975
TI  - Total synthesis of (+)-trans-dihydronarciclasine utilizing asymmetric conjugate
      addition.
AB  - A highly efficient short-step construction of the common phenanthridine skeleton
      of pancratistatin-class alkaloids was accomplished in enantiomerically pure form
      using chiral ligand-controlled asymmetric conjugate addition. The utility of the
      intermediate was demonstrated by the total synthesis of (+)-trans
      dihydronarciclasine with mild oxidation from an amine to an amide as a key step.

PMID- 23145977
TI  - Astrocytes and absence epilepsy.
AB  - This commentary discusses the importance of a new study entitled 'ONO-2506
      inhibits spike-wave discharges in a genetic animal model without affecting
      traditional convulsive tests via gliotransmission regulation' by Yamamura et al.
      () from Dr Okada's laboratory. The results from this study suggest that specific
      astrocyte modulating approaches should be developed for managing non-convulsive
      forms of epilepsy. In addition, the authors have advanced our understanding of
      astrocytic signalling and glial transmission. Their findings point to kynurenic
      acid as one of the key transmitters in the bi-directional communication between
      astrocytes and neurons. LINKED ARTICLE: This article is a commentary on the
      research paper by Yamamura et al., pp. 1088-1100 of this issue. To view this
      paper visit http://dx.doi.org/10.1111/j.1476-5381.2012.02132.x.

PMID- 23145974
TI  - OmpA-mediated rickettsial adherence to and invasion of human endothelial cells is
      dependent upon interaction with alpha2beta1 integrin.
AB  - Rickettsia conorii, a member of the spotted fever group (SFG) of the genus
      Rickettsia and causative agent of Mediterranean spotted fever, is an obligate
      intracellular pathogen capable of infecting various mammalian cell types. SFG
      rickettsiae express two major immunodominant surface cell antigen (Sca) proteins,
      OmpB (Sca5) and OmpA (Sca0). While OmpB-mediated entry has been characterized,
      the contribution of OmpA has not been well defined. Here we show OmpA expression
      in Escherichia coli is sufficient to mediate adherence to and invasion of non
      phagocytic human endothelial cells. A recombinant soluble C-terminal OmpA protein
      domain (954-1735) with predicted structural homology to the Bordetella pertussis
      pertactin protein binds mammalian cells and perturbs R. conorii invasion by
      interacting with several mammalian proteins including beta1 integrin. Using
      functional blocking antibodies, small interfering RNA transfection, and mouse
      embryonic fibroblast cell lines, we illustrate the contribution of alpha2beta1
      integrin as a mammalian ligand involved in R. conorii invasion of primary
      endothelial cells. We further demonstrate that OmpA-mediated attachment to
      mammalian cells is in part dependent on a conserved non-continuous RGD motif
      present in a predicted C-terminal 'pertactin' domain in OmpA.Our results
      demonstrate that multiple adhesin-receptor pairs are sufficient in mediating
      efficient bacterial invasion of R. conorii.

PMID- 23145978
TI  - Are we prepared to help low-resource communities cope with a severe influenza
      pandemic?
AB  - Recent research involving lab-modified H5N1 influenza viruses with increased
      transmissibility and the ongoing evolution of the virus in nature should remind
      us of the continuing importance of preparedness for a severe influenza pandemic.
      Current vaccine technology and antiviral supply remain inadequate, and in a
      severe pandemic, most low-resource communities will fail to receive adequate
      medical supplies. However, with suitable guidance, these communities can take
      appropriate actions without substantial outside resources to reduce influenza
      transmission and care for the ill. Such guidance should be completed, and support
      provided to developing countries to adapt it for their settings and prepare for
      implementation.

PMID- 23145979
TI  - The active site of melanopsin: the biological clock photoreceptor.
AB  - The nonvisual ocular photoreceptor melanopsin, found in the neurons of vertebrate
      inner retina, absorbs blue light and triggers the "biological clock" of mammals
      by activating the suprachiasmatic nuclei (a small region of the brain that
      regulates the circadian rhythms of neuronal and hormonal activities over 24 h
      cycles). The structure of melanopsin, however, has yet to be established. Here,
      we propose for the first time a structural model of the active site of mouse
      melanopsin. The homology model is based on the crystal structure of squid
      rhodopsin (lambda(max) = 490 nm) and shows a maximal absorbance (lambda(max) =
      447 nm) consistent with the observed absorption of the photoreceptor. The 43 nm
      spectral shift is due to an increased bond-length alternation of the protonated
      Schiff base of 11-cis-retinal chromophore, induced by N87Q mutation and water
      mediated H-bonding interactions with the Schiff base linkage. These findings,
      analogous to spectral changes observed in the G89Q bovine rhodopsin mutant,
      suggest that single site mutations can convert photopigments into visual light
      sensors or nonvisual sensory photoreceptors.

PMID- 23145981
TI  - Mixed-valence heptanuclear iron complexes with ferromagnetic interaction.
AB  - Three new Prussian blue analogues, heptanuclear mixed-valence iron complexes of
      the type [Fe(II)(CN)(6){Fe(III)(1(-2H))}(6)]Cl(2).nH(2)O, were synthesized and
      structurally and spectrally characterized, and their magnetic properties were
      investigated (1(-2H)  corresponds to doubly deprotoned Schiff-base pentadentate
      ligands 1a, N,N'-bis(2-hydroxybenzylidene)-1,5-diamino-3-azapentane, 1b, N,N'
      bis(3-ethoxy-2-hydroxybenzylidene)-1,7-diamino-4-azaheptane, or 1c, N,N'-bis(3
      methoxy-2-hydroxybenzylidene)-1,6-diamino-3-azahexane). These compounds were
      formed by assembling the [Fe(CN)(6)](4-) building block with mononuclear
      complexes of the [Fe(1(-2H))Cl] type.  X-ray structure analysis revealed that the
      complexes adopt a star-like architecture: the Fe(II) ion lies at the very center,
      and on its octahedral nodes the Fe(III) sites are coordinated in the Fe(II)-C=N
      Fe(III) manner. The Schiff-base pentadentate ligand moiety 1(-2H) coordinates a
      single Fe(III) center in two complexes 3b and 3c. Ligands 1a(-2H) in the complex
      cation of 3a adopt an unusual coordination mode: three donor atoms of the same
      ligand (one O and two N) coordinate one Fe(III), whereas the remaining N' and O'
      donor atoms coordinate the neighboring Fe(III) center creating  the
      {Fe(ON(2))(N'O')N"} chromophore involving two 1a(-2H) ligand moieties. Moreover,
      three Fe(III) centers are interconnected with three 1a(-2H) ligands in such a
      manner that two {Fe(III)(3)(1a(-2H))(3)} units form two intramolecular rings.
      Magnetic investigation of the heptanuclear complexes revealed the high-spin state
      of all six Fe(III) coordination sites (s = 5/2), while the very central Fe(II)
      site is in the low-spin state (s = 0). At low temperature, the ferromagnetic
      exchange interactions stay evident for all three complexes.  Mossbauer spectra of
      compounds 3a and 3b revealed a presence of two different doublets for both
      compounds: the major doublet is related to six Fe(III) high-spin coordination
      sites and the minor doublet refers to the low-spin very central Fe(II).

PMID- 23145980
TI  - Passive pressure-diameter relationship and structural composition of rat
      mesenteric lymphangions.
AB  - BACKGROUND: Lymph flow depends on both the rate of lymph production by tissues
      and the extent of passive and active pumping. Here we aim to characterize the
      passive mechanical properties of a lymphangion in both mid-lymphangion and valve
      segments to assess regional differences along a lymphangion, as well as
      evaluating its structural composition. METHODS AND RESULTS: Mesenteric lymphatic
      vessels were isolated and cannulated in a microchamber for pressure-diameter (P
      D) testing. Vessels were inflated from 0 to 20 cmH(2)O at a rate of 4
      cmH(2)O/min, and vessel diameter was continuously tracked, using an inverted
      microscope, video camera, and custom LabVIEW program, at both mid-lymphangion and
      valve segments. Isolated lymphatic vessels were also pressure-fixed at 2 and 7
      cmH(2)O and imaged using a nonlinear optical microscope (NLOM) to obtain collagen
      and elastin structural information. We observed a highly nonlinear P-D response
      at low pressures (3-5 cmH(2)O), which was modeled using a three-parameter
      constitutive equation. No significant difference in the passive P-D response was
      observed between mid-lymphangion and valve regions. NLOM imaging revealed an
      inner elastin layer and outer collagen layer at all locations. Lymphatic valve
      leaflets were predominantly elastin with thick axially oriented collagen bands at
      the insertion points. CONCLUSIONS: We observed a highly nonlinear P-D response at
      low pressures (3-5 cmH(2)O) and developed the first constitutive equation to
      describe the passive P-D response for a lymphangion. The passive P-D response did
      not vary among regions, in agreement with the composition of elastin and collagen
      in the lymphatic wall.

PMID- 23145982
TI  - Presurgical evaluation of Fontan connection options for patients with apicocaval
      juxtaposition using computational fluid dynamics.
AB  - Apicocaval juxtaposition (ACJ) is a rare congenital heart defect associated with
      single ventricle physiology where optimal positioning of the Fontan conduit for
      completion of total cavopulmonary connection (TCPC) is still controversial. In
      ACJ, the cardiac apex is ipsilateral with the inferior vena cava (IVC), risking
      kinking and collapse of the Fontan conduit at the apex of the heart. The purpose
      of this study is to evaluate two viable routes for Fontan conduit connection in
      patients with ACJ, using computational fluid dynamics. Internal energy loss
      evaluations were used to determine contribution of conduit curvature to the
      energy efficiency of each cavopulmonary anastomosis configuration. This
      percentage of energy loss contribution was found to be greater in the case of a
      curved extracardiac conduit connection (44%, 4.1 mW) traveling behind the
      ventricular apex, connecting the IVC to the left pulmonary artery, than the
      straighter lateral tunnel conduit (6%, 1.4 mW) installed through the ventricular
      apex. In contrast, net energy loss across the anastomosis was significantly lower
      with extracardiac TCPC (9.3 mW) in comparison with lateral tunnel TCPC (23.2 mW),
      highlighting that a curved Fontan conduit is favorable provided that it is traded
      off for a superior cavopulmonary connection efficiency. Therefore, a relatively
      longer and curved Fontan conduit has been demonstrated to be a suitable
      connection option independent of anatomical situations.

PMID- 23145983
TI  - The CRISPRs, they are a-changin': how prokaryotes generate adaptive immunity.
AB  - All organisms need to continuously adapt to changes in their environment. Through
      horizontal gene transfer, bacteria and archaea can rapidly acquire new traits
      that may contribute to their survival. However, because new DNA may also cause
      damage, removal of imported DNA and protection against selfish invading DNA
      elements are also important. Hence, there should be a delicate balance between
      DNA uptake and DNA degradation. Here, we describe prokaryotic antiviral defense
      systems, such as receptor masking or mutagenesis, blocking of phage DNA
      injection, restriction/modification, and abortive infection. The main focus of
      this review is on CRISPR (clustered regularly interspaced short palindromic
      repeats)/Cas (CRISPR-associated), a prokaryotic adaptive immune system. Since its
      recent discovery, our biochemical understanding of this defense system has made a
      major leap forward. Three highly diverse CRISPR/Cas types exist that display
      major structural and functional differences in their mode of generating
      resistance against invading nucleic acids. Because several excellent recent
      reviews cover all CRISPR subtypes, we mainly focus on a detailed description of
      the type I-E CRISPR/Cas system of the model bacterium Escherichia coli K12.

PMID- 23145984
TI  - Vocal fold insufficiency: medialization laryngoplasty vs calcium hydroxylapatite
      microspheres (Radiesse Voice(r)).
AB  - CONCLUSION: The choice of technique will depend on the glottic gap observed by
      stroboscopy, the alteration of the Voice Handicap Index (VHI) and the recorded
      values of harmonics-to-noise ratio (HNR), jitter and shimmer, and the general
      health, age and underlying pathology. There are statistically significant
      differences between the values of VHI, shimmer and jitter in favour of those
      cases operated on within 6 months of diagnosis. Alternatives are discussed.
      OBJECTIVES: This study analysed and compared the functional, morphological and
      acoustic results, after surgery, through the techniques of medialization
      thyroplasty and infiltration of biomaterials to correct incomplete closure of the
      glottis. METHODS: A total of 21 patients with dysphonia due to vocal fold
      insufficiency (13 women and 8 men) and ages ranging between 30 and 65 years (mean
      age 40.84, SD 12.5) were evaluated. The material used for augmentation surgery
      consisted of calcium hydroxylapatite microspheres. Measurements (VHI, jitter,
      shimmer and HNR) were performed before surgery and at 6 and 24 months post
      intervention. RESULTS: Overall, statistically significant differences were
      observed relating to measurements (p < 0.01) and surgical techniques (p < 0.05)
      analyzed. In particular, these differences were located in pairs pre-surgery - 6
      months post-surgery and pre-surgery - post 24 months, in the four variables, and
      between the two techniques used in jitter (p = 0.008), HNR (p = 0.045) and VHI (p
      = 0.035).

PMID- 23145985
TI  - PomZ, a ParA-like protein, regulates Z-ring formation and cell division in
      Myxococcus xanthus.
AB  - Accurate positioning of the division site is essential to generate appropriately
      sized daughter cells with the correct chromosome number. In bacteria, division
      generally depends on assembly of the tubulin homologue FtsZ into the Z-ring at
      the division site. Here, we show that lack of the ParA-like protein PomZ in
      Myxococcus xanthus resulted in division defects with the formation of chromosome
      free minicells and filamentous cells. Lack of PomZ also caused reduced formation
      of Z-rings and incorrect positioning of the few Z-rings formed. PomZ localization
      is cell cycle regulated, and PomZ accumulates at the division site at midcell
      after chromosome segregation but prior to FtsZ as well as in the absence of FtsZ.
      FtsZ displayed cooperative GTP hydrolysis in vitro but did not form detectable
      filaments in vitro. PomZ interacted with FtsZ in M. xanthus cell extracts. These
      data show that PomZ is important for Z-ring formation and is a spatial regulator
      of Z-ring formation and cell division. The cell cycle-dependent localization of
      PomZ at midcell provides a mechanism for coupling cell cycle progression and Z
      ring formation. Moreover, the data suggest that PomZ is part of a system that
      recruits FtsZ to midcell, thereby, restricting Z-ring formation to this position.

PMID- 23145986
TI  - Ultrafast folding and molecular dynamics of a linear hydrophobic beta-hairpin.
AB  - The first computational study of the folding and dynamics of a hydrophobic beta
      hairpin containing a central heterochiral diproline segment is reported. Linear
      hydrophobic sequences containing centrally positioned diproline motifs,
      heterochiral (DL/LD) and homochiral (LL/DD)), are investigated for their ability
      to form beta-hairpins. Heterochiral diproline motifs (LD/DL) reveal the formation
      of stable beta-hairpins with the backbone adopting beta-turn conformation and the
      formation of backbone hydrogen bonds with antiparallel cross-strand registry,
      whereas the homochiral diproline (LL/DD) containing sequences tend to adopt PPII
      helix conformation. The competition between the beta-turn formation and the
      backbone H-bond ladder of the antiparallel beta-strands in heterochiral diproline
      containing sequences is employed to validate the hypothesis that beta-turn
      formation precedes inter-strand registry in the folding of a beta-hairpin
      ("zipper" mechanism). The observation of noncanonical hydrogen bonds leads to a
      folded beta-hairpin-like conformation and points to the existence of relatively
      stable transition state intermediates, between the unfolded (extended) and folded
      (beta-hairpin) states. The MD simulations are in excellent agreement with the
      experimental studies on the model system and constitute the very first
      computational investigation of the folding and dynamics of a completely
      hydrophobic synthetic beta-hairpin containing heterogeneous residues of mixed
      chirality. 

PMID- 23145987
TI  - Early extensive viremia, but not rs8099917 genotype, is the only predictor for
      cholestatic hepatitis C after living-donor liver transplantation.
AB  - AIM: Cholestatic hepatitis C is one of the most serious but still unaddressed
      disorders after liver transplantation. METHODS: In this study, we analyzed 49
      patients who underwent living-donor liver transplantation (LDLT) to treat
      hepatitis C virus (HCV) infection. RESULTS: Five patients developed cholestatic
      hepatitis C, with total bilirubin of 15.2 +/- 3.1 mg/dL at diagnosis 6.2 +/- 1.0
      weeks after LDLT. Univariate analysis showed that larger graft to standard liver
      volume ratio, higher HCV RNA titer at 2 weeks, earlier peak HCV RNA titer and
      cytomegalovirus infection were the significant risk factors. The development of
      cholestatic hepatitis C was not significantly associated with interleukin-28B
      genotype (rs8099917); four out of five affected patients had the T/T genotype.
      Multivariate analysis showed that higher HCV RNA titer at 2 weeks was the only
      significant factor (P = 0.026) for the development of cholestatic hepatitis C.
      Receiver-operator curve analysis showed that that HCV RNA titer of more than 7.2
      log10 IU/mL was the optimal cut-off for characterizing cholestatic hepatitis C.
      All of the patients were serum HCV RNA negative after treatment with pegylated
      interferon and ribavirin and all the patients are alive. CONCLUSION: Early
      extensive viremia, but not the rs8099917 genotype, was the only predictor for
      cholestatic hepatitis C after LDLT.

PMID- 23145988
TI  - Laminin-gamma1 chain and stress inducible protein 1 synergistically mediate PrPC
      dependent axonal growth via Ca2+ mobilization in dorsal root ganglia neurons.
AB  - Prion protein (PrP(C)) is a cell surface glycoprotein that is abundantly
      expressed in nervous system. The elucidation of the PrP(C) interactome network
      and its significance on neural physiology is crucial to understanding
      neurodegenerative events associated with prion and Alzheimer's diseases. PrP(C)
      co-opts stress inducible protein 1/alpha7 nicotinic acetylcholine receptor
      (STI1/alpha7nAChR) or laminin/Type I metabotropic glutamate receptors (mGluR1/5)
      to modulate hippocampal neuronal survival and differentiation. However, potential
      cross-talk between these protein complexes and their role in peripheral neurons
      has never been addressed. To explore this issue, we investigated PrP(C)-mediated
      axonogenesis in peripheral neurons in response to STI1 and laminin-gamma1 chain
      derived peptide (Ln-gamma1). STI1 and Ln-gamma1 promoted robust axonogenesis in
      wild-type neurons, whereas no effect was observed in neurons from PrP(C) -null
      mice. PrP(C) binding to Ln-gamma1 or STI1 led to an increase in intracellular
      Ca(2+) levels via distinct mechanisms: STI1 promoted extracellular Ca(2+) influx,
      and Ln-gamma1 released calcium from intracellular stores. Both effects depend on
      phospholipase C activation, which is modulated by mGluR1/5 for Ln-gamma1, but
      depends on, C-type transient receptor potential (TRPC) channels rather than
      alpha7nAChR for STI1. Treatment of neurons with suboptimal concentrations of both
      ligands led to synergistic actions on PrP(C)-mediated calcium response and
      axonogenesis. This effect was likely mediated by simultaneous binding of the two
      ligands to PrP(C). These results suggest a role for PrP(C) as an organizer of
      diverse multiprotein complexes, triggering specific signaling pathways and
      promoting axonogenesis in the peripheral nervous system.

PMID- 23145989
TI  - Granulomatosis with polyangiitis (Wegener's granulomatosis) in children: report
      of three cases with cutaneous manifestations and literature review.
AB  - Granulomatosis with polyangiitis (GPA), also known as Wegener's granulomatosis,
      is a rare disease in childhood. Of 39 GPA patients that we diagnosed during a 20
      year period, only 3 (7.7%) were younger than 18 years. We report the course of
      GPA in three girls whose disease started at the ages of 16, 11, and 6 years. All
      had cutaneous manifestations: the first had necrotizing vasculitis, the second
      had palpable purpura, and the third had right upper-eyelid edema and infiltration
      and proptosis caused by extraocular pseudotumor, initially histologically
      misdiagnosed as orbital immunoglobulin G4 (IgG4)-related disease. Unlike with
      skin vasculitis and glomerulonephritis, upper-airway and orbital inflammation
      were resistant to immunosuppressive therapy. Our report emphasizes that children
      presenting with cutaneous vasculitis, chronic eyelid swelling, sinusitis, or
      hoarseness should be tested for antineutrophil cytoplasmic antibodies. We
      emphasize that the upper-eyelid edema and infiltration, with histologic
      characteristics of orbital IgG4-related disease, may be the initial presentation
      of localized GPA in children, a feature that, until now, has been described only
      in adults.

PMID- 23145990
TI  - Ultrasound-responsive block copolymer micelles based on a new amplification
      mechanism.
AB  - A new approach for amplifying the effect of high-intensity focused ultrasound
      (HIFU) in disassembling amphiphilic block copolymer (BCP) micelles in aqueous
      solution was investigated. The diblock copolymer is comprised of a water-soluble
      poly(ethylene oxide) (PEO) block and a block of poly(2-(2-methoxyethoxy)ethyl
      methacrylate) (PMEO(2)MA) that is hydrophobic at temperatures above its lower
      critical solution temperature (LCST). We show that by introducing a small amount
      of HIFU-labile 2-tetrahydropyranyl methacrylate (THPMA) comonomer units into the
      PMEO(2)MA that forms the micelle core at T > LCST, an ultrasound irradiation of a
      micellar solution could induce the hydrolysis of THPMA groups. As a result, the
      LCST of the thermosensitive polymer increases due to the conversion of
      hydrophobic THPMA comonomer units onto hydrophilic methacrylic acid.
      Consequently, the BCP micelles disassemble without actually changing the solution
      temperature. In addition to the characterization results of transmittance
      measurements, variable-temperature (1)H NMR, SEM, and DLS, a (13)C NMR spectral
      analysis provided critical evidence for the hydrolysis reaction of THPMA groups
      under HIFU irradiation.

PMID- 23145991
TI  - Decision aids to improve informed decision-making in pregnancy care: a systematic
      review.
AB  - BACKGROUND: Rapid development in health care has resulted in an increasing number
      of screening and treatment options. Consequently, there is an urgency to provide
      people with relevant information about benefits and risks of healthcare options
      in an unbiased way. Decision aids help people to make decisions by providing
      unbiased non-directive research evidence about all treatment options. OBJECTIVE:
      To determine the effectiveness of decision aids to improve informed decision
      making in pregnancy care. SEARCH STRATEGY: We searched MEDLINE (1953-2011),
      EMBASE (1980-2011), CENTRAL (CENTRAL, the Cochrane Library; 2011, Issue 4),
      Psycinfo (1806-2011) and Research Registers of ongoing trials
      (www.clinicaltrials.gov, www.controlled-trials.com). SELECTION CRITERIA: We
      included randomised controlled trials comparing decision aids in addition to
      standard care. The study population needed to be pregnant women making actual
      decisions concerning their pregnancy. DATA COLLECTION AND ANALYSIS: Two
      independent researchers extracted data on quality of the randomised controlled
      trial (GRADE criteria), quality of the decision aid (IPDAS criteria), and outcome
      measures. Data analysis was undertaken by assessing group differences at first
      follow up after the interventions. MAIN RESULTS: Ten randomised controlled trials
      could be included. Pooled analyses showed that decision aids significantly
      increased knowledge, (weighted mean difference 11.06, 95% confidence interval
      4.85-17.27), decreased decisional conflict scores (weighted mean difference 
      3.66, 95% confidence interval -6.65 to -0.68) and decreased anxiety (weighted
      mean difference -1.56, 95% confidence interval -2.75 to -0.43). CONCLUSIONS: Our
      systematic review showed the positive effect of decision aids on informed
      decision making in pregnancy care. Future studies should focus on increasing the
      uptake of decision aids in clinical practice by identifying barriers and
      facilitators to implementation.

PMID- 23145992
TI  - Skin tissue water assessed via tissue dielectric constant measurements in persons
      with and without diabetes mellitus.
AB  - BACKGROUND: Skin changes in diabetes mellitus (DM) include possible increases in
      foot skin water content as interpreted from altered echogenicity in high
      frequency ultrasound images. The present goal was to investigate the possibility
      of undetected increased local skin water in persons with DM using a handheld
      portable rapid measuring device that measures the tissue dielectric constant
      (TDC) as an indicator of skin tissue water. SUBJECTS AND METHODS: TDC
      measurements were done bilaterally on 18 persons with DM and 18 persons without
      DM (NODM) at foot dorsum and anterior forearm to tissue depths of 0.5, 1.5, and
      2.5 mm. DM duration was 11.1 +/- 10.9 years. Age, body mass index, and blood
      pressures were not significantly different between groups. RESULTS: NODM and DM
      TDC values decreased with increasing depth at forearm but were depth independent
      at foot dorsum. All DM foot TDC values were significantly (P<0.05) greater than
      for NODM, with foot TDC values at 2.5 mm depth being 14.8% greater than in NODM.
      DM forearm TDC values were not significantly greater than NODM. CONCLUSIONS: A
      technology that characterizes local skin water in a rapid and noninvasive way has
      been used for the first time in persons with DM. The greater TDC value at the
      foot dorsum of the DM group is consistent with the presence of previously
      unrecognized increased fluid content. This suggests that there may be benefit
      utilizing this measurement method as a way to screen for early changes in foot
      skin features that may tend to cause DM-related edema.

PMID- 23145993
TI  - 'Straight from the horse's mouth': rethinking and reconfiguring services in
      Northern Ireland in response to suicidal young men.

PMID- 23145995
TI  - Facile synthesis of fully substituted dihydro-beta-carbolines via Bronsted acid
      promoted cascade reactions of alpha-indolyl propargylic alcohols with nitrones.
AB  - A straightforward synthesis of fully substituted beta-carbolines via Bronsted
      acid promoted cyclizations of alpha-indolyl propargylic alcohols with nitrones is
      described. The use of nitrones bearing alkenyl or electron-rich aryl groups as
      the R(4) substituent dramatically switches the reaction pathway to afford
      tetrasubstituted alkenes and amines, which is assumed to proceed through a
      rearrangement reaction involving N-O bond cleavage and 1,2-migration of the R(4)
      group to an adjacent nitrogen atom.

PMID- 23145994
TI  - Junction region of EWS-FLI1 fusion protein has a dominant negative effect in
      Ewing's sarcoma in vitro.
AB  - BACKGROUND: Ewing's sarcoma is a malignancy characterized by a specific 11:22
      chromosomal translocation which generates a novel EWS-FLI1 fusion protein
      functioning as an aberrant transcription factor. In the present study, we have
      further characterized the junction region of the EWS-FLI1 fusion protein.
      METHODS: In-silico model of EWS-FLI1 fusion protein was analysed for ligand
      binding sites, and a putative region (amino acid (aa) 251-343 of the type 1
      fusion protein) in the vicinity of the fusion junction was cloned and expressed
      using bacterial expression. The recombinant protein was characterized by Circular
      Dichroism (CD). We then expressed aa 251-280 ectopically in Ewing's sarcoma cell
      line and its effect on cell proliferation, tumorigenicity and expression of EWS
      FLI1 target genes were analysed. RESULTS: Our modelling analysis indicated that
      Junction region (aa 251-343) encompasses potential ligand biding sites in the EWS
      FLI1 protein and when expressed in bacteria was present as soluble form.
      Ectopically expressing this region in Ewing's sarcoma cells inhibited
      tumorigenicity, and EWS-FLI1 target genes indicating a dominant negative
      biological effect. CONCLUSIONS: Junction region can be exploited further as
      target for drug development in future to specifically target EWS-FLI1 in Ewing's
      Sarcoma.

PMID- 23145996
TI  - Rapid cytotoxicity screening platform for amyloid inhibitors using a membrane
      potential sensitive fluorescent probe.
AB  - The growing interest in membrane interactions of amyloidogenic proteins indicates
      that lipid binding and the regulation of membrane potential are critical to the
      onset and progression of neurodegenerative diseases such as Parkinson's (PD),
      Alzheimer's (AD), and prion diseases. Advancing the understanding of this field
      requires the application of varied biophysical and biological techniques designed
      to probe the characteristics and underlying mechanisms of membrane-peptide
      interactions. Therefore, the development of a rapid cytotoxicity evaluation
      system using a membrane potential-sensitive bis-oxonol fluorescent dye, DiBAC4(3)
      is reported here. The exposure of C-terminal truncated alpha-synuclein 119 (alpha
      Syn119) and amyloid-beta(1-42) (Abeta(1-42)) to U2-OS cell cultures resulted in
      an immediate, significant, and concentration-dependent increase in fluorescence
      response of DiBAC4(3). This response was strongly correlated with the
      cytotoxicity of alpha-Syn119 and Abeta(1-42) as determined by conventional CC8
      and ATP assays. Furthermore, the capacity of well-defined polyphenolic
      antioxidants (i.e., pyrroloquinoline quinone (PQQ), baicalein, (-)
      epigallocatechin-3-gallate (EGCG), and myricetin) to mitigate amyloid-induced
      cytotoxicity was evaluated using the developed biosensing system. We envisage
      that this work would accelerate the development of a rapid and cost-effective
      high-throughput screening platform in drug discovery for AD and PD.

PMID- 23145997
TI  - Outbreaks of influenza-like illness in long-term care facilities in Winnipeg,
      Canada.
AB  - BACKGROUND: Outbreaks of influenza-like illness (ILI) are common in long-term
      care facilities (LTCFs) and result in significant morbidity and mortality among
      residents. OBJECTIVES: We describe patterns of reported ILI outbreaks in LTCFs in
      Winnipeg, Canada, and examine LTCF and outbreak characteristics that influence
      the clinical outcomes of these outbreaks. METHODS: We analyzed the electronic
      records of all ILI outbreaks reported by LTCFs in Winnipeg from 2003 to 2011.
      Outbreak duration, ILI attack rates among staff and residents, and residents'
      death rates were calculated by presumed viral etiology, staff vaccination rates,
      type of influenza chemoprophylaxis used, and time to notification to public
      health. RESULTS: Of a total of 154 reported outbreaks, most (N=80) were
      attributed to influenza, and these outbreaks tended to have higher attack and
      death rates among LTCF residents compared with outbreaks caused by other
      respiratory viruses (12) or those of unknown etiology (62). About 92% of
      residents and 38% of staff of the average LTCFs were vaccinated. Chemoprophylaxis
      was used in 57.5% of influenza outbreaks. Regardless of presumed viral etiology,
      outbreaks reported within 3 days of onset ended sooner and had lower attack and
      mortality rates among residents. CONCLUSIONS: Influenza-like illness outbreaks
      still occur among highly immunized LTCF residents, so in addition to vaccination
      of staff and residents, it is important to maintain competent infection control
      practices. Early identification and notification to public health authorities and
      possibly early initiation of control measures could improve clinical outcomes of
      ILI outbreaks.

PMID- 23145998
TI  - Cinchona alkaloid amides/dialkylzinc catalyzed enantioselective desymmetrization
      of aziridines with phosphites.
AB  - The first highly enantioselective desymmetrization of aziridines with phosphites
      has been developed. Excellent yields and enantioselectivities were observed for
      the reaction with various aziridines using a new class of readily accessible
      chiral catalysts derived from 9-amino-9-deoxy-epi-cinchona alkaloids. In studies
      probing the reaction mechanism, we observed some complexes for the cinchona
      alkaloid amide-Zn(II) by ESI-MS analysis.

PMID- 23145999
TI  - Bisphenol A in chronic kidney disease.
AB  - The estrogenic endocrine-disrupting substance bisphenol A (BPA) is extensively
      used as a starting material for a variety of consumer plastic products including
      dialyzer materials. The present study was performed to explore plasma BPA levels
      in patients with impaired renal function and to investigate if dialyzers
      differing in elutable BPA influence plasma levels in patients on maintenance
      hemodialysis. In vitro BPA was eluted from high-flux polyethersulfone (PUREMA H,
      referred as PUR-H), high-flux polysulfone (referred as HF-PSu), and low-flux
      polysulfone (referred as LF-PSu) dialyzers by recirculation with water for 180
      min. In a cross-sectional clinical study, plasma BPA levels of outpatients with
      different stages of chronic kidney disease (CKD) from four different centers were
      determined. Furthermore, in a prospective, randomized, and crossover setting, 18
      maintenance dialysis patients were subjected successively to 4 weeks of thrice
      weekly hemodialysis with each LF-PSu, HF-PSu, and PUR-H. In addition, the
      fractions of protein-bound and free BPA were determined in a subset of dialysis
      patients. The mass of BPA eluted from the blood compartments in vitro under
      aqueous conditions varied for the three dialyzers being very low for PUR-H (6.2
      +/- 2.5 ng; P < 0.001), intermediate for HF-PSu (48.1 +/- 7.7 ng), and highest
      for LF-PSu (140.8 +/- 38.7 ng; P < 0.01). In 152 prevalent patients with CKD
      enrolled in the cross-sectional trial, plasma BPA started to rise after stage 3.
      Maintenance hemodialysis patients had more than six times higher BPA
      concentrations than patients with CKD stage 5 not yet on dialysis (10.0 +/- 6.6
      vs. 1.6 +/- 1.8 ng/mL; P < 0.001). The BPA concentrations highly and inversely
      correlated with renal function. In the randomized controlled study, the plasma
      BPA concentrations were highly elevated compared with healthy controls (range 9.1
      +/- 4.5-12.0 +/- 6.0 ng/mL vs. <=0.2 +/- 0.1 ng/mL; P < 0.001), but no change of
      the plasma levels was observed during hemodialysis with any of the three
      dialyzers in the course of a single treatment and over a period of 4 weeks. The
      protein-bound fraction of plasma BPA in the dialysis patients was 74 +/- 5%.
      Renal function and, most likely, the total quantity of ingested BPA are essential
      parameters affecting plasma BPA concentrations. Dialyzers are one additional
      source of BPA, but differences in the elutable BPA content are not associated
      with a significant effect on BPA plasma levels in Western European maintenance
      dialysis patients. Due to high protein binding, the removal of BPA by
      hemodialysis is limited.

PMID- 23146000
TI  - Safe fetal platelet genotyping: new developments.
AB  - BACKGROUND: Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is due to
      maternal alloimmunization against fetal platelet (PLT) antigens. Antenatal
      management strategies have been developed to avoid complications such as
      intracranial hemorrhage. The aim of this study was to set up two reliable,
      noninvasive fetal genotyping assays to determine the fetal risk in pregnancies in
      which the father is heterozygous for the offending antigen. This study focused on
      human PLT antigen (HPA)-1, the most frequently implicated antigen in FNAIT in
      Caucasians. STUDY DESIGN AND METHODS: Two assays based on cell-free fetal DNA
      extracted from maternal blood samples and on real-time polymerase chain reaction
      (QPCR) were developed: an allele-specific QPCR specifically targeting the
      polymorphic sequence in HPA-1 and the study of the variation in the high
      resolution melting curve of amplicons containing the polymorphic region. RESULTS:
      All results from the 49 samples obtained from 29 pregnant women were consistent
      with expectations. Six women were compatible with their fetuses (three HPA-1aa
      women and three HPA-1bb women), 41 HPA-1bb women were incompatible with their
      fetuses, as were two HPA-1aa women. CONCLUSION: Two fetal PLT genotyping assays
      on maternal blood samples proved to be reliable as of 15 weeks of gestation,
      thereby avoiding invasive techniques such as amniocentesis.

PMID- 23146001
TI  - Prediction of DNA-binding proteins from relational features.
AB  - BACKGROUND: The process of protein-DNA binding has an essential role in the
      biological processing of genetic information. We use relational machine learning
      to predict DNA-binding propensity of proteins from their structures.
      Automatically discovered structural features are able to capture some
      characteristic spatial configurations of amino acids in proteins. RESULTS:
      Prediction based only on structural relational features already achieves
      competitive results to existing methods based on physicochemical properties on
      several protein datasets. Predictive performance is further improved when
      structural features are combined with physicochemical features. Moreover, the
      structural features provide some insights not revealed by physicochemical
      features. Our method is able to detect common spatial substructures. We
      demonstrate this in experiments with zinc finger proteins. CONCLUSIONS: We
      introduced a novel approach for DNA-binding propensity prediction using
      relational machine learning which could potentially be used also for protein
      function prediction in general.

PMID- 23146002
TI  - Historical overview of the rationale for the pharmacological use of prolonged
      release fampridine in multiple sclerosis.
AB  - Multiple sclerosis is a progressive demyelinating neurological disease resulting
      in long-term disability, commonly manifesting in walking impairment and reduced
      quality of life. The use of the potassium channel blocker fampridine, chemically
      4-aminopyridine, as an immediate-release formulation to improve action potential
      conduction in demyelinated axons was hampered by adverse events, including
      seizures. The prolonged-release formulation of fampridine (known as modified- or
      sustained-release fampridine in some countries and dalfampridine extended release
      in the USA) has a longer apparent half-life and a lower peak plasma concentration
      versus immediate-release fampridine formulations, sustaining its duration of
      action and reducing the incidence of adverse events. Prolonged-release fampridine
      is the first drug specifically licensed to improve walking in patients with
      multiple sclerosis, and has been shown to consistently improve walking ability in
      a third of patients. Prolonged-release fampridine Timed-Walk Responders showed
      both clinically significant improvements in walking speed and in patient-reported
      walking ability.

PMID- 23146003
TI  - Roles of acetone and diacetone alcohol in coordination and dissociation reactions
      of uranyl complexes.
AB  - Combined collision-induced dissociation mass spectrometry experiments with DFT
      and MP2 calculations were employed to elucidate the molecular structures and
      energetics of dissociation reactions of uranyl species containing acetone and
      diacetone alcohol ligands. It is shown that solutions containing diacetone
      alcohol ligands can produce species with more than five oxygen atoms available
      for coordination. Calculations confirm that complexes with up to four diacetone
      alcohol ligands can be energetically stable but that the effective number of
      atoms coordinating with uranium in the equatorial plane does not exceed five.
      Water elimination reactions of diacetone alcohol ligands are shown to have two
      coordination-dependent reaction channels, through formation of mesityl oxide
      ligands or formation of alkoxide and protonated mesityl oxide species. The
      present results provide an explanation for the implausible observation of
      "[UO(2)(ACO)(6,7,8)](2+)" in and observed water-elimination reactions from
      purportedly uranyl-acetone complexes (Rios, D.; Rutkowski, P. X.; Van Stipdonk,
      M. J.; Gibson, J. K. Inorg. Chem. 2011, 50, 4781).

PMID- 23146004
TI  - In praise of introversion.

PMID- 23146005
TI  - Communication and patient safety in simulation for mental health nursing
      education.
AB  - The Joint Commission on Accreditation of Healthcare Organizations (JCAHO) found
      that 65% of medical sentinel events or medical errors are associated with
      communication breakdowns. In addition to the JCAHO, The Institute of Medicine, in
      their Core Competencies for health care professional education, recommend
      improvement in professional communication, collaboration, and a patient-centered
      approach to provide safety. Consistency of opportunities for students to practice
      their communication and collaboration skills is limited based on the variety of
      clinical experiences that are available. Simulation would provide consistency in
      students' experiences. Students can practice giving a structured report,
      providing and receiving peer feedback, and obtaining patient feedback in a safe
      setting through a simulation experience. A structured hand-off shift report using
      a technique such as SBAR communication has been found to improve patient safety
      in health care environments. This paper examines the implementation of a
      simulation experience for students taking a Mental Health course in a Bachelor of
      Science in Nursing (BSN) Program to support their practice of patient and
      professional communication, as well as, collaboration skills with a patient
      centered approach using a standardized patient simulation.

PMID- 23146006
TI  - Drawing the line: a case study of ambivalence in sibling support for adults with
      complex needs.
AB  - The purpose of this article is to illuminate the dynamics of sibling group
      support when one sibling has complex needs accompanied by difficult behaviors. A
      case study of sibling support for a twenty-year-old woman with a disability, a
      mental health issue, and addictions, drawn from the perspectives of her full
      brother, her half-brother, and their mother, is presented. The brothers express
      ambivalence between devotion to supporting their sister and limits to the support
      they feel able to provide. The limits the brothers place on their support allow
      them to adhere to their values, preserve their energy and, ultimately, sustain
      their ability to provide support.

PMID- 23146007
TI  - Using critical ethnography to explore issues among immigrant and refugee women
      seeking help for postpartum depression.
AB  - Critical ethnography was used as a pragmatic research methodology to explore the
      postpartum depression (PPD) experiences of immigrant and refugee women. We
      examined the social, political, economic, and historical factors that affected
      the help-seeking behavior of these women during PPD episodes. The critical
      ethnography method allowed participants to share their experiences with each
      other and afforded opportunities to the researchers to acknowledge and validate,
      rather than simply observe and record, their testimony. This study of PPD thus
      increased our awareness and understanding of the health issues of immigrant and
      refugee women.

PMID- 23146008
TI  - To be strategically struggling against resignation: the lived experience of being
      cared for in forensic psychiatric care.
AB  - To be referred to care in forensic psychiatric services can be seen as one of the
      most comprehensive encroachments society can impose upon a person's life, as it
      entails a limitation of the individual's freedom with no time limit. This study
      focuses upon patients' experiences of their life situation in forensic
      psychiatric wards. Using a Reflective Lifeworld Research approach founded in
      phenomenology, we analysed 11 qualitative interviews with patients cared for on a
      maximum security unit in a Swedish forensic psychiatric service. Results show how
      forensic psychiatric care can be non-caring with only moments of good care, from
      the patient's perspective. By using different strategies, the patients attempt to
      adapt to the demands of the caregivers in order to gain privileges. At the same
      time the patients are lacking meaningful and close relationships and long to get
      away from the system of forensic care. Being cared for entails struggling against
      an approaching overwhelming sense of resignation.

PMID- 23146009
TI  - Perceptions of barriers to physical health care for people with serious mental
      illness: a review of the international literature.
AB  - Premature death and poorer access to quality care for physical health concerns is
      common for people diagnosed with serious mental illness (SMI). However, there is
      lack of clarity regarding the nature of barriers encountered at different points
      in the physical health care process, and the level of consistency of these
      barriers both among countries, and between consumers with SMI and health care
      staff. The current narrative review integrates views of consumers and health care
      staff on barriers to physical health care. It involved a search of CINAHL,
      Proquest, and Web of Science, for peer-reviewed papers published between 2005 and
      June 2012, for studies of perceptions of barriers to physical health care,
      published in English. Despite variations in health care systems among countries,
      there is agreement between consumers and health care staff that division between
      physical and mental health care and stigma of mental illness act as barriers to
      all phases of the physical health care process. This uniformity is grounds for
      international policy development (in general public health and within mental
      health nursing) for reforms that improve the physical health care, quality of
      life, and longevity of people with serious mental illness.

PMID- 23146010
TI  - Workplace bullying influences women's engagement in the workforce.
AB  - Workplace bullying creates hostile work environments, affects mental and physical
      health, and has social, economic, and career implications. Over 70% of targets of
      workplace bullying become unemployed either by losing their jobs or by leaving
      voluntarily. In a grounded theory study, we explored how experiencing workplace
      bullying and its health consequences affected 40 Canadian women. Further, I
      examined whether women stayed at or left workplaces after being bullied, how they
      left, and the influences on whether they stayed or left. Implications of this
      study are that bullied women and the organizations for which they work need to be
      assisted to manage this experience more effectively.

PMID- 23146011
TI  - Undergraduate college students' perceptions of psychiatric nurses.
AB  - We surveyed undergraduate students' perceptions of psychiatric nurses'
      effectiveness and analyzed other sources of data. Students reported that
      psychiatric nurses' strengths include helping in situations that involve
      psychiatric symptoms, mental health evaluation, and drug abuse. Psychiatric
      nurses also were said to be effective when helping an individual with psychiatric
      symptoms, such as delusions and hallucinations. Friends or associates, common
      knowledge, school and education, and movies are some sources by which students
      learn about psychiatric nurses. Sources that provided less influential
      information include insurance carriers, newspapers, and personal experience.

PMID- 23146012
TI  - The relationship among neuroticism, extraversion, and depression in the HUNT
      Study: in relation to age and gender.
AB  - The purpose of this study was to examine the relationship between personality and
      depression in a general population in relation to gender and age. The Nord
      Trondelag Health Study (2006-2008), a large cross-sectional survey, was used. The
      sample consists of 35,832 men (16,104) and women (19,728) aged 20-89 years,
      living in the Nord-Trondelag County of Norway, with valid ratings on the
      depression subscale of the Hospital Anxiety and Depression Scale (HADS) and
      Eysenck Personality Questionnaire (EPQ). This study demonstrates a relationship
      between depression and both neuroticism and extraversion in a general population.
      Older people score low more often on Extraversion (E) than younger people.
      Interactions were observed between neuroticism and age, gender, and extraversion
      with depression. The interaction term indicates a high score on Neuroticism (N)
      enhanced by introversion, older age, and being a male with depression. The
      findings suggest that health professionals may need to put extra effort into the
      care of patients with low extraversion and high neuroticism, in order to help
      those patients avoid depression.

PMID- 23146013
TI  - Mental health and relational self-management experiences of patients with type 2
      diabetes and stage 3 chronic kidney disease.
AB  - Self-management (SM) behaviors reduce disease burden from advancing diabetic
      kidney disease. From a parent study about patients' transition experience to SM,
      this study report presents coping resources that support SM and barriers from two
      focus group interviews (n = 6). Ethnographic analysis identified two patterns:
      (a) mental health self-management characterized by coping, and (b) relational
      self-management characterized by social support. Practice implications include
      focused assessment of perceived social support and social network, dating
      advisement, and workplace management. Future study considerations include inquiry
      about diabetes and dating relationships and workplace resources for SM support.

PMID- 23146014
TI  - Full circle-old drugs prove more beneficial than newer agents for schizophrenia:
      a case report.
AB  - A 55-year-old female with a diagnosis of schizophrenia currently resides in an
      assisted living facility in a large metropolitan suburb. For approximately 25
      years, the patient was relegated to a life of poor symptom control and social
      adjustment, largely due to nonadherence, relapse, and rehospitalization. The
      patient experienced a trial-and-error approach to drug therapy, which resulted in
      reliance on the older or first generation agents for symptom improvement. This
      case supports the assertion that the second-generation or atypical antipsychotics
      used to treat schizophrenia are no better than older drugs in terms of efficacy
      or tolerability.

PMID- 23146015
TI  - Discrimination and health outcomes.

PMID- 23146016
TI  - The concept of "the will to thrive" in mental health.
AB  - Mental health nursing is focused on patients moving along the continuum between
      failing and thriving in terms of emotional functioning. This differs dramatically
      from a medical model of disease/cure. A variety of nursing theorists have both
      directly and indirectly identified the importance of patient's "will to thrive"
      although this term has never been used. Peplau spoke of self-efficacy and self
      esteem. Barrett's model focuses on the patient's participation in their own
      recovery as a key component. This article explores the concept, akin to failure
      to thrive in infants, of the will to thrive in the chronically ill and its role
      in assessment and nursing intervention. A particular emphasis on the importance
      of patient responsibility is identified as vital to the process of true change.

PMID- 23146019
TI  - FadD3 is an acyl-CoA synthetase that initiates catabolism of cholesterol rings C
      and D in actinobacteria.
AB  - The cholesterol catabolic pathway occurs in most mycolic acid-containing
      actinobacteria, such as Rhodococcus jostii RHA1, and is critical for
      Mycobacterium tuberculosis (Mtb) during infection. FadD3 is one of four predicted
      acyl-CoA synthetases potentially involved in cholesterol catabolism. A DeltafadD3
      mutant of RHA1 grew on cholesterol to half the yield of wild-type and accumulated
      3aalpha-H-4alpha(3'-propanoate)-7abeta-methylhexahydro-1,5-indanedione (HIP),
      consistent with the catabolism of half the steroid molecule. This phenotype was
      rescued by fadD3 of Mtb. Moreover, RHA1 but not DeltafadD3 grew on HIP. Purified
      FadD3(Mtb) catalysed the ATP-dependent CoA thioesterification of HIP and its
      hydroxylated analogues, 5alpha-OH HIP and 1beta-OH HIP. The apparent specificity
      constant (k(cat) /K(m) ) of FadD3(Mtb) for HIP was 7.3 +/- 0.3 * 10(5)  M(-1)  s(
      1) , 165 times higher than for 5alpha-OH HIP, while the apparent K(m) for CoASH
      was 110 +/- 10 MUM. In contrast to enzymes involved in the catabolism of rings A
      and B, FadD3(Mtb) did not detectably transform a metabolite with a partially
      degraded C17 side-chain. Overall, these results indicate that FadD3 is a HIP-CoA
      synthetase that initiates catabolism of steroid rings C and D after side-chain
      degradation is complete. These findings are consistent with the actinobacterial
      kstR2 regulon encoding ring C/D degradation enzymes.

PMID- 23146021
TI  - Han ethnicity-specific type 2 diabetic treatment from traditional Chinese
      medicine?
AB  - Insulin-degrading enzyme (IDE) gene is one of the type 2 diabetes mellitus
      susceptibility genes specific to the Han Chinese population. IDE, a zinc
      metalloendopeptidase, is a potential target for controlling insulin degradation.
      Potential lead compounds for IDE inhibition were identified from traditional
      Chinese medicine (TCM) through virtual screening and evaluation of their
      pharmacokinetic properties of absorption, distribution, metabolism, excretion,
      and toxicity. Molecular dynamics (MD) simulation was performed to validate the
      stability of complexes from docking simulation. The top three TCM compounds,
      dihydrocaffeic acid, isopraeroside IV, and scopolin, formed stable H-bond
      interactions with key residue Asn139, and were linked to active pocket residues
      His108, His112, and Glu189 through zinc. Torsion angle trajectories also
      indicated some stable interactions for each ligand with IDE. Molecular level
      analysis revealed that the TCM candidates might affect IDE through competitive
      binding to the active site and steric hindrance. Structural feature analysis
      reveals that high amounts of hydroxyl groups and carboxylic moieties contribute
      to anchor the ligand within the complex. Hence, we suggest the top three TCM
      compounds as potential inhibitor leads against IDE protein to control insulin
      degradation for type 2 diabetes mellitus. An animated interactive 3D complement
      (I3DC) is available in Proteopedia at http://proteopedia.org/w/Journal:JBSD:29. 

PMID- 23146020
TI  - Co-expression of Na(V)beta subunits alters the kinetics of inhibition of voltage
      gated sodium channels by pore-blocking MU-conotoxins.
AB  - BACKGROUND AND PURPOSE: Voltage-gated sodium channels (VGSCs) are assembled from
      two classes of subunits, a pore-bearing alpha-subunit (NaV 1) and one or two
      accessory beta-subunits (NaV betas). Neurons in mammals can express one or more
      of seven isoforms of NaV 1 and one or more of four isoforms of NaV beta. The
      peptide MU-conotoxins, like the guanidinium alkaloids tetrodotoxin (TTX) and
      saxitoxin (STX), inhibit VGSCs by blocking the pore in NaV 1. Hitherto, the
      effects of NaV beta-subunit co-expression on the activity of these toxins have
      not been comprehensively assessed. EXPERIMENTAL APPROACH: Four MU-conotoxins (MU
      TIIIA, MU-PIIIA, MU-SmIIIA and MU-KIIIA), TTX and STX were tested against NaV
      1.1, 1.2, 1.6 or 1.7, each co-expressed in Xenopus laevis oocytes with one of NaV
      beta1, beta2, beta3 or beta4 and, for NaV 1.7, binary combinations of thereof.
      KEY RESULTS: Co-expression of NaV beta-subunits modifies the block by MU
      conotoxins: in general, NaV beta1 or beta3 co-expression tended to increase kon
      (in the most extreme instance by ninefold), whereas NaV beta2 or beta4 co
      expression decreased kon (in the most extreme instance by 240-fold). In contrast,
      the block by TTX and STX was only minimally, if at all, affected by NaV beta
      subunit co-expression. Tests of NaV beta1 : beta2 chimeras co-expressed with NaV
      1.7 suggest that the extracellular portion of the NaV beta subunit is largely
      responsible for altering MU-conotoxin kinetics. CONCLUSIONS AND IMPLICATIONS:
      These results are the first indication that NaV beta subunit co-expression can
      markedly influence MU-conotoxin binding and, by extension, the outer vestibule of
      the pore of VGSCs. MU-Conotoxins could, in principle, be used to
      pharmacologically probe the NaV beta subunit composition of endogenously
      expressed VGSCs.

PMID- 23146022
TI  - Avidin-biotin interaction mediated peptide assemblies as efficient gene delivery
      vectors for cancer therapy.
AB  - Gene therapy offers a bright future for the treatment of cancers. One of the
      research highlights focuses on smart gene delivery vectors with good
      biocompatibility and tumor-targeting ability. Here, a novel gene vector self
      assembled through avidin-biotin interaction with optimized targeting
      functionality, biotinylated tumor-targeting peptide/avidin/biotinylated cell
      penetrating peptide (TAC), was designed and prepared to mediate the in vitro and
      in vivo delivery of p53 gene. TAC exhibited efficient DNA-binding ability and low
      cytotoxicity. In in vitro transfection assay, TAC/p53 complexes showed higher
      transfection efficiency and expression amount of p53 protein in MCF-7 cells as
      compared with 293T and HeLa cells, primarily due to the specific recognition
      between tumor-targeting peptides and receptors on MCF-7 cells. Additionally, by
      in situ administration of TAC/p53 complexes into tumor-bearing mice, the
      expression of p53 gene was obviously upregulated in tumor cells, and the tumor
      growth was significantly suppressed. This study provides an alternative and
      unique strategy to assemble functionalized peptides, and the novel self-assembled
      vector TAC developed is a promising gene vector for cancer therapy.

PMID- 23146023
TI  - Pregestational body mass index is related to neonatal abdominal circumference at
      birth--a Danish population-based study.
AB  - OBJECTIVES: To examine the impact of maternal pregestational body mass index
      (BMI) and smoking on neonatal abdominal circumference (AC) and weight at birth.
      To define reference curves for birth AC and weight in offspring of healthy,
      nonsmoking, normal weight women. DESIGN: Population-based study. SETTING: Data
      from the Danish Medical Birth Registry. POPULATION: All live singletons without
      congenital malformations in Denmark 2004-10. METHODS: Data on 366,886 singletons
      at 35(+0) to 41(+6) weeks(+days) of gestation were extracted and analysed using
      multivariate linear regressions. MAIN OUTCOME MEASURES: Birth AC and weight in
      relation to pregestational maternal BMI, maternal smoking and medical conditions
      (any). RESULTS: Birth AC and weight increased with increasing pregestational BMI,
      and decreased with smoking (P < 0.0001). Reference curves were created for
      offspring of healthy, nonsmoking mothers with normal pregestational BMI. Mean AC
      ranged from 30.1 cm and 30.2 cm at 35 weeks of gestation to 33.9 cm and 34.1 cm
      at 41 weeks of gestation, for girls and boys, respectively. Mean birthweight
      ranged from 2581 and 2666 g at 35 weeks to 3705 and 3852 g at 41 weeks of
      gestation for girls and boys, respectively. Pregestational BMI correlated more to
      the Z score of birthweight than to the Z score of AC (P < 0.0001). CONCLUSION:
      Birth AC and weight are affected by maternal smoking status and pregestational
      BMI. Pregestational BMI correlated more to birthweight than to AC. Using data
      from healthy, nonsmoking mothers with normal pregestational BMI we have provided
      new reference curves for birth AC and birthweight.

PMID- 23146024
TI  - The experience of weight gain as a result of taking second-generation
      antipsychotic medications: the mental health consumer perspective.
AB  - This interpretive qualitative study aimed to describe and construct the meaning
      of the experience of living with the weight gain associated with second
      generation antipsychotics. A qualitative study that incorporated the tenets of
      phenomenology and utilized in-depth interviews was conducted with eight mental
      health consumers. Thematic analysis resulted in three themes: Grappling with the
      weight; Living with the consequences of being overweight; and Experiencing
      negative emotions about the weight gain. The findings indicate that consumers
      struggle to manage the insatiable appetite and the related weight gain associated
      with second-generation antipsychotic medication, as well as the numerous
      associated physical and emotional issues. Adherence with prescribed second
      generation antipsychotic medication was also affected and a number of the
      participants indicated they had ceased or considered ceasing their medication
      because of the weight gain associated with the drugs.

PMID- 23146025
TI  - Linear congenital molluscum contagiosum on the coccygeal region.
AB  - Congenital molluscum contagiosum is rare but has been reported previously. We
      present a unique case of linear congenital molluscum on the coccygeal region. To
      make a correct diagnosis, avoid unnecessary examination, and start appropriate
      treatment as soon as possible, it is beneficial for dermatologists to be aware
      that molluscum contagiosum can present at birth and can be linear. 

PMID- 23146026
TI  - Semitransparent nanostructured films for imaging mass spectrometry and optical
      microscopy.
AB  - Semitransparent porous silicon substrates have been developed for pairing
      nanostructure-initiator mass spectrometry (NIMS) imaging with traditional optical
      based microscopy techniques. Substrates were optimized to generate the largest
      NIMS signal while maintaining sufficient transparency to allow visible light to
      pass through for optical microscopy. Using these substrates, both phase-contrast
      and NIMS images of phospholipids from a scratch-wounded cell monolayer were
      obtained. NIMS images were generated using a spatial resolution of 14 MUm.
      Coupled with further improvements in spatial resolution, this approach may allow
      for the localization of intact biological molecules within cells without the need
      for labeling.

PMID- 23146027
TI  - Predictive markers for neoadjuvant chemotherapy in advanced squamous cell
      carcinoma of maxillary sinus: Preliminary report.
AB  - CONCLUSION: ERCC 1 seems to be promising as a predictive marker for response to
      neoadjuvant chemotherapy (NAC) and early decision for surgery in advanced
      squamous cell carcinoma (SCC) of the maxillary sinus. OBJECTIVES: This study
      aimed to find a possible relation of ERCC1 or XRCC1 expression with response to
      NAC and prognosis in advanced SCC of the maxillary sinus. METHODS: From 1998 to
      2006, 17 patients with advanced SCC of the maxillary sinus received NAC at the
      Seoul National University Hospital. The expression of ERCC1 and XRCC1 was
      assessed by immunohistochemistry. Complete and partial remissions were
      categorized as the chemo-sensitive group. On the other hand, stable and
      progressive diseases were categorized as the chemo-resistant group. RESULTS: Of
      these 17 patients, 1 had complete remission, 6 had partial remission, 4 had
      stable disease, and 6 had progression of disease. The 5-year survival rate was
      40% for all 17 patients. The expression of ERCC1 and XRCC1 was not correlated
      with nodal or distant metastasis. With a cut-off value of 65%, patients with
      higher ERCC1 scores showed chemo-resistance and survival disadvantage over those
      with lower ERCC1 scores. However, XRCC1 did not show a significant effect on the
      response to NAC.

PMID- 23146028
TI  - PDGFRalpha/beta and VEGFR2 polymorphisms in colorectal cancer: incidence and
      implications in clinical outcome.
AB  - BACKGROUND: Angiogenesis plays an essential role in tumor growth and metastasis,
      and is a major target in cancer therapy. VEGFR and PDGFR are key players involved
      in this process. The purpose of this study was to assess the incidence of genetic
      variants in these receptors and its potential clinical implications in colorectal
      cancer (CRC). METHODS: VEGFR2, PDGFRalpha and PDGFRbeta mutations were evaluated
      by sequencing their tyrosine kinase domains in 8 CRC cell lines and in 92 samples
      of patients with CRC. Correlations with clinicopathological features and survival
      were analyzed. RESULTS: Four SNPs were identified, three in PDGFRalpha [exon 12
      (A12): c.1701A>G; exon 13 (A13): c.1809G>A; and exon 17 (A17): c.2439+58C>A] and
      one in PDGFRbeta [exon 19 (B19): c.2601A>G]. SNP B19, identified in 58% of tumor
      samples and in 4 cell lines (LS174T, LS180, SW48, COLO205), was associated with
      higher PDGFR and pPDGFR protein levels. Consistent with this observation, 5-year
      survival was greater for patients with PDGFR B19 wild type tumors (AA) than for
      those harboring the G-allele genotype (GA or GG) (51% vs 17%; p=0.073).
      Multivariate analysis confirmed SNP B19 (p=0.029) was a significant prognostic
      factor for survival, independent of age (p=0.060) or TNM stage (p<0.001).
      CONCLUSIONS: PDGFRbeta exon 19 c.2601A>G SNP is commonly encountered in CRC
      patients and is associated with increased pathway activation and poorer survival.
      Implications regarding its potential influence in response to PDGFR-targeted
      agents remain to be elucidated.

PMID- 23146029
TI  - Can telomere shortening in human peripheral blood leukocytes serve as a disease
      biomarker of Friedreich's ataxia?
AB  - Enhanced oxidative stress and inflammation contribute to telomere erosion.
      Friedreich's ataxia is a neurodegenerative disorder caused by a reduction in
      frataxin expression that results in mitochondrial dysfunction and oxidative
      damage. Furthermore, frataxin deficiency induces a strong activation of
      inflammatory genes and neuronal death. We investigated telomere length (TL) in
      peripheral blood leukocytes of 37 patients with Friedreich's ataxia and 36
      controls. We noted a significant telomere shortening in patients with
      Friedreich's ataxia compared to healthy controls (p=0.03). We also found a
      correlation between TL and disease duration (p=0.001). Our observations lead to
      the hypothesis that the TL of human peripheral blood leukocytes may serve as a
      biomarker of Friedreich's ataxia that could be used as an outcome measure in
      clinical trials.

PMID- 23146030
TI  - Copper-catalyzed enantioselective synthesis of axially chiral allenes.
AB  - A simple copper-catalyzed enantioselective synthesis of axially chiral
      chloroallenes from the propargylic dichlorides is reported, employing a catalytic
      amount of easily prepared SimplePhos ligand. Exclusive formation of the desired
      allenes was observed with good enantioselectivities (ee's 62-96%). Further
      transformations to trisubstituted allenes or terminal alkynes with a propargylic
      quaternary carbon center keep a high level of enantiopurity.

PMID- 23146031
TI  - Role of Bcl-2 in tumour cell survival and implications for pharmacotherapy.
AB  - OBJECTIVES: Bcl-2 is a protein that inhibits apoptosis, leading to cell survival.
      The Bcl-2 family has six different anti-apoptotic proteins, three pro-apoptotic
      proteins that are similar in structure, and other integrating proteins that
      function as promotors or inhibitors in the progression of apoptosis. In this
      discussion paper, we provide an overview of apoptosis, the role of Bcl-2 in
      normal cellular and molecular processes, and the role of Bcl-2 in tumour cell
      survival. It focuses primarily on anti-apoptotic Bcl-2, its activation in cancer,
      the manner in which it regulates the intrinsic and extrinsic mechanisms of
      apoptosis, and its broad molecular interactions with other critical proteins in
      the cell. Certain cancer treatments are reviewed and related directions for the
      future are presented. KEY FINDINGS: Apoptosis is common to all organisms - for
      eukaryotes it is a normal process of development and regeneration. The rate at
      which apoptosis occurs is critical to the survival of the organism, as too much
      can lead to the onset of degenerative diseases such as dementia, and too little
      may lead to cancer. FKBP-38 is a binding protein that has been discovered to be
      upregulated in highly aggressive cancers and binds to Bcl-2 rather than the pro
      apoptotics to induce a state of hyper-mitosis. A short binding protein (Nur-77)
      provides new insights into Bcl-2 'masking'. Nurr-77 binds to Bcl-2 and exposes
      the BH3 domain, transforming it from a cancer promoter to an unorthodox cancer
      inhibitor. This presents in itself an interesting and exciting opportunity -
      increasing the rate of apoptosis in neoplastic cells that are usually protected
      by Bcl-2 activity at the mitochondria. SUMMARY: Development of drugs in the form
      of BH3-only and BH123 mimetic drugs provide a interesting avenue for cancer
      therapy for the future. Drugs that can either promote, or mimic anti-IAP activity
      such as Smac/Diablo would certainly be productive, thereby inducing apoptosis.
      Medicinal usage which can effectively suppress FKBP38 in Bcl-2-dependent cancers
      would provide further arsenal to combat apoptotic irregularities, particularly a
      treatment that is more dominant than kinetin riboside. WAVE-1 inhibitors may
      effectively suppress the phosphorylation of Bcl-2, thereby potentially reducing
      hyper-mitosis and increasing apoptosis. Recent findings shed molecular light on
      PDT, namely ER stress, and potential for anti-cancer therapy via either apoptosis
      or autophagy. A drug that can effectively upregulate Nurr-77, thereby masking the
      anti-apoptotic properties of Bcl-2, would indeed be life-saving for cancer
      patients.

PMID- 23146032
TI  - Role of fetuin-A in atherosclerosis associated with diabetic patients.
AB  - OBJECTIVES: Fetuin-A is a circulating glycoprotein, formed in the liver. It
      regulates bone remodelling and calcium metabolism. Fetuin-A has adipogenic
      properties, so fat accumulation in the liver may be associated with higher levels
      of fetuin-A. Fetuin-A is an inhibitor of the phosphorylation of the insulin
      receptor tyrosine kinase. KEY FINDINGS: High concentrations of fetuin-A in humans
      causes insulin resistance. Insulin sensitivity is also found to be increased in
      fetuin-A knockout mice. Fetuin-A has been shown to cause insulin resistivity in
      type-2 diabetes mellitus and worsens the pro-atherogenic milieu. SUMMARY: Fetuin
      A should be considered as a hepatic bio-marker. Vascular diseases like
      atherosclerosis are major causes of disability in patients with diabetes
      mellitus.

PMID- 23146033
TI  - Intranasal delivery of insulin via the olfactory nerve pathway.
AB  - OBJECTIVES: Intranasal delivery has been shown to target peptide therapeutics to
      the central nervous system (CNS) of animal models and induce specific
      neurological responses. In an investigation into the pathways by which intranasal
      administration delivers insulin to the CNS, this study has focused on the direct
      delivery of insulin from the olfactory mucosa to the olfactory bulbs via the
      olfactory nerve pathway. METHODS: Nasal and olfactory tissues of mice were imaged
      with fluorescent and electron microscopy 30 min following intranasal
      administration. KEY FINDINGS: Macroscopic analysis confirmed delivery to the
      anterior regions of the olfactory bulbs. Confocal microscopy captured delivery
      along the olfactory nerve bundles exiting the nasal mucosa, traversing the
      cribriform plate and entering the bulbs. With electron microscopy, insulin was
      found within cells of the olfactory nerve layer and glomerular layer of the
      olfactory bulbs. CONCLUSIONS: These results demonstrated that intranasal
      administration of labelled insulin targeted the CNS through the olfactory nerve
      pathway in mice.

PMID- 23146034
TI  - Inhibition of CYP3A4 by 6',7'-dihydroxybergamottin in human CYP3A4 over-expressed
      hepG2 cells.
AB  - OBJECTIVES: We previously established HepG2-GS-3A4, a cell line from
      hepatoblastoma with overexpression of human CYP3A4 and glutamine synthetase (GS).
      We further reported that these cells can be applied for screening inhibitors of
      CYP3A4 in vitro. The purpose of this study was to determine whether our CYP3A4
      overexpresed cell could be applied to evaluate mechanisms of CYP3A4 inhibition by
      6',7'-dihydroxybergamottin (DHB), which is one of the major furanocoumarins in
      grapefruit juice, by using these cells. METHODS: Nifedipine oxidation, activity
      and protein expression of NADPH-cytochrome reductase (POR) of HepG2-GS-3A4 cell
      were measured. CO-binding spectrumassay in microsomal fraction of the cells was
      also evaluated. KEY FINDINGS: DHB and ketoconazole, a well-known inhibitor of
      CYP3A4, inhibited nifedipine oxidation in a concentration-dependent manner. DHB
      at a concentration of 3.0 um, sufficient to inhibit the nifedipine oxidation,
      decreased POR activity; however, ketoconazole at a concentration of 0.9 um,
      sufficient to inhibit the oxidation, did not affect the activity. The expression
      of POR protein in HepG2-GS-3A4 cells was not changed by either DHB or
      ketoconazole. The expression of CYP3A4 mRNA and protein was not changed by the
      addition of DHB or ketoconazole. DHB also reduced the absorption rate at 450 nm
      in a CO-binding spectrum assay without alteration of the wavelength of maximum
      absorption. The mean absorption value at 450 nm slightly decreased with
      ketoconazole; however, the difference was not significant. CONCLUSIONS: We
      concluded that inhibition of CYP3A4 activity by DHB includes the inhibition of
      POR activity. HepG2-GS-3A4 might be a good tool to evaluate the mechanisms.

PMID- 23146035
TI  - Antinociceptive activity of carvacrol (5-isopropyl-2-methylphenol) in mice.
AB  - OBJECTIVES: Carvacrol (5-isopropyl-2-methylphenol) is a monoterpenic phenol which
      is present in the essential oil of oregano and thyme. We have investigated the
      behavioural effects of carvacrol in animal models of pain, such as acetic acid
      induced abdominal constriction, formalin and hot-plate tests in mice. The
      spontaneous motor activity of animals treated with carvacrol was investigated
      using open-field and rotarod tests. METHODS: Carvacrol was administered orally,
      at single doses of 50 and 100 mg/kg while indometacin (5 mg/kg), morphine (7.5
      mg/kg) and diazepam (2 mg/kg) were used as standard drugs. Naloxone (1 mg/kg) and
      l-arginine (150 mg/kg) were used to elucidate the possible antinociceptive
      mechanism of carvacrol on acetic acid-induced abdominal constriction and formalin
      tests. KEY FINDINGS: The results showed that carvacrol produced significant
      inhibitions on nociception in the acetic acid-induced abdominal constriction,
      formalin and hot-plate tests. In the open-field and rotarod tests carvacrol did
      not significantly impair the motor performance. The effect of the highest dose of
      carvacrol in mice in the acetic acid-induced abdominal constriction and formalin
      tests were not reversed by naloxone or l-arginine. CONCLUSIONS: Based on these
      results, it has been suggested that carvacrol presents antinociceptive activity
      that may not act through the opioid system nor through inhibition of the nitric
      oxide pathway.

PMID- 23146036
TI  - 7-O-galloyl-D-sedoheptulose ameliorates renal damage triggered by reactive oxygen
      species-sensitive pathway of inflammation and apoptosis.
AB  - OBJECTIVES: This study was carried out to verify the preventive effects of 7-O
      galloyl-d-sedoheptulose (GS), a phenolic compound isolated from Corni Fructus,
      underlying diabetic renal damage in type 2 diabetes. METHODS: GS was orally
      administered to db/db mice at doses of 20 and 100 mg/kg body weight per day for
      six weeks, and its effects were compared with those of the vehicle in db/db and
      m/m mice. KEY FINDINGS: In the serum and kidney, biochemical factors and
      expression of protein related to nicotinamide adenine dinucleotide phosphate
      (NADPH) oxidase, apoptosis and inflammation were examined. GS treatment
      attenuated serum and renal oxidative stress through reduction of reactive oxygen
      species and lipid peroxidation and increase in the ratio of glutathione and its
      oxidised form. Importantly, GS reduced renal protein expression of Nox-4 and
      p22(phox) (one of the subunits of NADPH oxidase), pro-apoptotic factors (such as
      Bax and cytochrome c) and nuclear factor-kappa B-targeting pro-inflammatory
      inducible nitric oxide synthase and cyclooxygenase-2. CONCLUSIONS: These
      renoprotective effects of GS were achieved through attenuation of diabetes
      induced oxidative stress and its sensitive protein expression associated with
      inflammation and apoptosis in db/db mice.

PMID- 23146037
TI  - Reversal of P-glycoprotein-mediated multidrug resistance of human hepatic cancer
      cells by Astragaloside II.
AB  - OBJECTIVES: Chemoresistance is the main obstacle encountered in cancer treatment
      and is frequently associated with multidrug resistance (MDR). Astragaloside is a
      saponin which is widely used in traditional Chinese medicine. It has been
      reported that Astragaloside has antitumour effects on hepatocellular carcinoma
      Bel-7402 cells in vitro and in vivo. The purpose of this study was to examine the
      effects of Astragaloside II on the reversal of MDR and its molecular mechanism in
      vitro. METHODS: In this study, Bel-7402 and Bel-7402/FU cell lines were used as
      the experimental model. Drug sensitivity was determined using the 3-(4,5
      Dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay, accumulation and
      efflux of Rh123 were analyzed by flow cytometer, the mRNA level of mdr1 was
      determined by RT-PCR and the protein levels of P-glycoprotein (P-gp) and mitogen
      activated protein kinase were determined by Western blot. KEY FINDINGS:
      Astragaloside II (0.08 mg/ml) showed strong potency to increase 5-fluorouracil
      cytotoxicity toward 5-fluorouracil-resistant human hepatic cancer cells Bel
      7402/FU. The mechanism of Astragaloside II on P-gp-mediated MDR demonstrated that
      Astragaloside II significantly increased the intracellular accumulation of
      rhodamine 123 via inhibition of P-gp transport function. Based on the analysis of
      P-gp and mdr1 gene expression using Western blot and RT-PCR, the results revealed
      that Astragaloside II could downregulate the expression of the P-gp and mdr1
      gene. In addition, Astragaloside II suppressed phosphorylation of extracellular
      signal regulated kinase 1/2, p38 and c-Jun N-terminal kinase. CONCLUSIONS: The
      results suggested that Astragaloside II is a potent MDR reversal agent and may be
      a potential adjunctive agent for hepatic cancer chemotherapy.

PMID- 23146038
TI  - Antifibrosis effects of triterpene acids of Eriobotrya japonica (Thunb.) Lindl.
      leaf in a rat model of bleomycin-induced pulmonary fibrosis.
AB  - OBJECTIVE: The aim of this study was to investigate the prophylactic effect and
      some mechanisms of action of triterpene acids of loquat (TAL) on bleomycin A5
      induced pulmonary fibrosis rats. METHODS: A model of pulmonary fibrosis was
      induced by injecting rats with a single dose of bleomycin A5 (5 mg/kg) into the
      trachea. From the second day, rats in the preventive groups were treated with TAL
      (50, 150 or 450 mg/kg) or dexamethasone (1.2 mg/kg). On the 28th day after
      medication, the rats were killed and haematoxylin-eosin or masson staining was
      used to evaluate the degree of pulmonary fibrosis. Tumour necrosis factor-alpha
      (TNF-alpha) and transforming growth factor-beta1 (TGF-beta1) levels in alveolar
      macrophage culture supernatant were detected by ELISA. The mRNA expression of TNF
      alpha and TGF-beta1 in alveolar macrophage was observed by RT-PCR. KEY FINDINGS:
      Lung histopathological examination showed TAL could ameliorate the structure of
      the lung and alleviate fibrogenesis. At the same time, TAL (150 or 450 mg/kg dose
      group) could reduce the expression of TNF-alpha and TGF-beta1 in alveolar
      macrophage of rats with pulmonary fibrosis at either the protein or mRNA level.
      CONCLUSIONS: TAL had a positive prophylactic effect on lung fibrosis, which might
      have been related to its reduction on TNF-alpha or TGF-beta1 expression in the
      alveolar macrophage of pulmonary fibrosis rats.

PMID- 23146039
TI  - In-vitro inhibitory effect of Tualang honey on cytochrome P450 2C8 activity.
AB  - OBJECTIVES: To investigate the effect of Tualang honey on cytochrome P450 2C8
      (CYP2C8) activity in vitro using an amodiaquine N-desethylase assay. METHODS:
      CYP2C8 and NADPH cytochrome P450 reductase was cotransformed, expressed and
      harvested. The incubation assay contained expressed proteins, MgCl(2), NADP,
      glucose 6-phosphate, glucose-6-phosphate dehydrogenase, potassium phosphate
      buffer, and amodiaquine. The rate of conversion of amodiaquine to
      desethylamodiaquine, the metabolite, was determined using a high performance
      liquid chromatography (HPLC) method. The inhibition parameters, IC50
      (concentration of inhibitor causing 50% inhibition of original enzyme activity)
      and apparent inhibition constant (K(i) ) values were determined. KEY FINDINGS:
      The recombinant proteins were successfully expressed and used to investigate the
      effect of Tualang honey on CYP2C8 activity. The activity was measured by the rate
      of metabolism of amodiaquine to desethylamodiaquine determined using a
      successfully developed HPLC method. Kinetic parameters as determined by nonlinear
      least-squares regression and evaluated with Aikeike's goodness of fit criteria
      revealed that Tualang honey competitively inhibited CYP2C8 activity in a dose
      dependent manner. Maximum inhibition of 80% occurred at 0.01% honey. The IC50 and
      K(i) values were (10.0 +/- 3.0) * 10(-3) % and (5.1 +/- 0.5) * 10(-3) % w/v,
      respectively. CONCLUSIONS: This study has provided evidence for the in vitro
      inhibition of CYP2C8-mediated amodiaquine N-desethylase activity by Tualang
      honey. It revealed that honey, through this inhibition, may have the potential to
      cause in-vivo drug-food interaction with drugs metabolized by CYP2C8.

PMID- 23146040
TI  - Effects of St John's wort and its active constituents, hypericin and hyperforin,
      on isolated rat urinary bladder.
AB  - OBJECTIVES: To investigate the effect of St John's wort (SJW) and its active
      constituents hypericin and hyperforin on detrusor smooth muscle contractility and
      their possible neuroprotective role against ischaemic-like conditions, which
      could arise during overactive bladder disease. METHODS: In whole bladders,
      intrinsic nerves underwent electrical field stimulation (EFS). The effect of
      drugs on the contractile response and its recovery in reperfusion phase (R) was
      monitored at different concentrations during 1 or 2 h of anoxia-glucopenia (A-G)
      and the first 30 min of R. The effects of the drugs were also investigated on rat
      detrusor muscle strips contracted with carbachol, KCl and electrically. KEY
      FINDINGS: SJW has spasmolytic activity, which increases with increasing
      concentration and it worsens the damage induced by A-G/R on rat urinary bladder.
      Hypericin and hyperforin had no effect during ischemic-like conditions but they
      both exert a dual modulation of rat detrusor strips contraction. At high
      micromolar concentrations they showed a relaxing effect, but at submicromolar
      range hypericin increased the plasma membrane depolarisation and hyperforin
      showed a stimulatory effect on the cholinergic system. CONCLUSIONS: The results
      of our study showed that SJW and its constituents could modulate urinary bladder
      contractility and even worsen A-G/R injury.

PMID- 23146041
TI  - Relaxant effects of the essential oil of Mentha pulegium L. in rat isolated
      trachea and urinary bladder.
AB  - OBJECTIVES: We evaluated the relaxant activity of the essential oil of Mentha
      pulegium L. (EOMP) and pulegone in rat isolated tracheal and bladder smooth
      muscles. METHODS: ISOMETRIC contractions of isolated tracheal and bladder strips
      from male Wistar rats were induced by KCl (K60; 60 mm) or acetylcholine (ACh; 10
      um). EOMP and its majory compound pulegone were incubated, after contracting
      agent, with the tissues in cumulating concentrations. KEY FINDINGS: EOMP (3-300
      ug/ml) inhibited the contractions induced by ACh and K60 in both tissues, but was
      more effective against the contractions induced by K60 in trachea (IC50 = 40.47
      +/- 3.27 ug/ml) compared with ACh. Its relaxant action rules out ganglia and NO
      participation. Pulegone (10(-7) to 10(-3 ) m) inhibited the contractions induced
      by ACh and K60 in both tissues. EOMP concentration-dependently inhibited the
      contractions evoked by addition of CaCl(2) in depolarised trachea, suggesting
      inhibition of extracellular calcium entry. CONCLUSIONS: These findings suggests
      that EOMP induced relaxant responses in pre-contracted smooth muscles of rat
      trachea and bladder, which are likely to be mediated via inhibition of calcium
      entry, mainly by its major compound, pulegone. These effects are coherent with
      the popular use of EOMP as an antispasmodic agent.

PMID- 23146042
TI  - Isolation, modification and cytotoxic evaluation of flavonoids from Rhododendron
      hainanense.
AB  - OBJECTIVES: The aim of this study was to search for antitumour activity of
      flavonoid compounds. The cytotoxic activity of these compounds in vitro was
      evaluated against the human leukaemia (HL-60) and human hepatoma (SMMC-7721) cell
      lines. METHODS: Eight natural flavonoids (1-8) were isolated from the aerial
      parts of Rhododendron hainanense and a series of modified flavonoid derivatives
      (9-18) were obtained from the natural product matteucinol (1), using simple
      synthetic methods. Antitumour inhibitory activity of these flavonoids was
      assessed using the sulforhodamine B method. KEY FINDINGS: Most of the compounds
      exhibited good pharmacological activity and the preliminary structure-activity
      relationships were described. Within the series of flavonoid derivatives in this
      study, compounds 3 (2,3-dihydro-5-hydroxy-7-methoxy-2-(4-methoxyphenyl)-6,8
      dimethyl-4H-1-benzopyran-4-one) and 16 (5-hydroxy-7, 4'-dimethoxy-6, 8
      dimethylflavan) exhibited strong inhibitory activity against the HL-60 cell line
      with IC50 values (the drug concentration that resulted in a 50% reduction in cell
      viability or inhibition of the biological activity) of 15.2 and 13.2 um,
      respectively. CONCLUSIONS: Renewed attention to flavonoid derivatives revealed
      the possibility that compounds 3 and 16 could be considered as lead compounds for
      the development of new antitumour agents. Our results have not only enriched the
      family of active flavonoids from natural sources, but have encouraged the
      synthesis of flavonoid analogues for improving cytotoxic activity.

PMID- 23146043
TI  - Hepatic cytochrome P450 mediates interaction between warfarin and Coleus
      forskohlii extract in vivo and in vitro.
AB  - OBJECTIVES: This study aimed to determine whether Coleus forskohlii extract (CFE)
      influences the anticoagulant action of warfarin in mice in vivo and its
      relationship with hepatic cytochrome P450 (CYP). METHODS: Mice were fed various
      doses of CFE standardised with 10% forskolin in a normal diet for one week, or in
      protein diets containing 7% and 20% casein (low and normal) for four weeks. They
      were then administered with warfarin by gavage on the last two days of the
      treatment regimen, and blood coagulation parameters, as well as hepatic CYP, were
      analysed at 18 h after the last dose. Direct interaction between CFE and
      forskolin with CYP2C was evaluated in vitro. KEY FINDINGS: CFE dose dependently
      increased hepatic total CYP content and S-warfarin 7-hydroxylase activity at a
      dietary level of >=0.05%. Warfarin-induced anticoagulation was attenuated by CFE
      in parallel with CYP induction. The findings were similar in mice fed diets
      containing CFE and different ratios of protein. CFE directly inhibited CYP2C
      activity in mouse and human liver microsomes in vitro, whereas forskolin was only
      slightly inhibitory. CONCLUSIONS: CFE attenuates the anticoagulant action of
      warfarin by inducing hepatic CYP2C; thus, caution is required with the
      combination of warfarin and dietary supplements containing CFE.

PMID- 23146044
TI  - S100A12: a noninvasive marker of inflammation in inflammatory bowel disease.
AB  - Inflammatory bowel diseases are incurable conditions that feature gut
      inflammation. Standard markers have inadequate sensitivity and specificity.
      S100A12 is a new fecal marker that has promise as a non-invasive indicator of gut
      inflammation. This article reviews recent studies focusing on S100A12 and
      highlights the current and potential roles of this biomarker.

PMID- 23146046
TI  - Spontaneous redox synthesis of the charge transfer material TTF4[SVMo11O40].
AB  - The charge-transfer material TTF-SV(IV)Mo(11)O(40) (TTF = tetrathiafulvalene) was
      prepared by a spontaneous redox reaction between TTF and the vanadium-substituted
      polyoxometalate (n-Bu(4)N)(3)[SV(V)Mo(11)O(40)] in both solution  and solid state
      phases. Single crystal X-ray diffraction gave the stoichiometry
      TTF(4)[SVMo(11)O(40)].2H(2)O.2CH(2)Cl(2), with the single V atom positionally
      disordered with eight Mo atoms over the whole alpha-Keggin polyanion
      [SVMo(11)O(40)](4-). Raman spectra support the 1+ charge assigned to the oxidized
      TTF deduced from bond lengths, and elemental and voltammetric analysis also are
      consistent with this formulation. Scanning electron microscopy images showed a
      rod-type morphology for the new charge-transfer material. The conductivity of the
      solid at room temperature is in the semiconducting range. The TTF and (n
      Bu(4)N)(3)[SV(V)Mo(11)O(40)] solids also undergo a rapid interfacial reaction, as
      is the case with TTF and TCNQ (TCNQ = tetracyanoquinodimethane) solids. EPR
      spectra at temperatures down to 2.6 K confirm the presence of two paramagnetic
      species, V(IV) and the oxidized TTF radical. Spectral evidence shows that the TTF
      SV(IV)Mo(11)O(40) materials prepared from either solution or solid state
      reactions are equivalent. The newly isolated TTF-SV(IV)Mo(11)O(40) material
      represents a new class of TTF-polyoxometalate compound having dual electrical and
      magnetic functionality derived from both the cationic and anionic components.

PMID- 23146047
TI  - A detrimental reaction at the molybdenum back contact in Cu2ZnSn(S,Se)4 thin-film
      solar cells.
AB  - Experimental proof is presented for a hitherto undetected solid-state reaction
      between the solar cell material Cu(2)ZnSn(S,Se)(4) (CZTS(e)) and the standard
      metallic back contact, molybdenum. Annealing experiments combined with Raman and
      transmission electron microscopy studies show that this aggressive reaction
      causes formation of MoS(2) and secondary phases at the CZTS|Mo interface during
      thermal processing. A reaction scheme is presented and discussed in the context
      of current state-of-the-art synthesis methods for CZTS(e). It is concluded that
      alternative back contacts will be important for future improvements in CZTS(e)
      quality.

PMID- 23146045
TI  - Laparoscopic spleen-preserving No. 10 lymph node dissection for advanced proximal
      gastric cancer in left approach: a new operation procedure.
AB  - BACKGROUND: To explore the feasibility of laparoscopic spleen-preserving No. 10
      lymph node dissection in a left-sided approach for advanced proximal gastric
      cancer. METHODS: The clinical data of 32 patients with advanced proximal gastric
      cancer who underwent laparoscopic spleen-preserving No. 10 lymph node dissection
      from June 2010 to December 2011 were analyzed. RESULTS: Laparoscopic spleen
      preserving No. 10 lymph node dissection using a left-sided approach was
      successfully performed for all patients without open conversion. The mean
      operation time was 206.4+/-54.3 minutes, mean intraoperative blood loss was
      68.2+/-34.1 ml, mean number of No. 10 lymph nodes dissected was 2.8+/-2.1, mean
      number of positive No. 10 lymph nodes was 0.6+/-1.2, and the incidence of No. 10
      lymph node metastasis was 11.6%. The mean postoperative hospital stay was 11.3+/
      1.5 days. The postoperative morbidity rate was 9.4%, and there was no
      postoperative death. Splenic lobar vessels of all 32 patients were anatomically
      classified and divided into three types: 4 patients had a single lobar vessel, 22
      had two lobar vessels and 6 had three lobar vessels. CONCLUSIONS: Laparoscopic
      spleen-preserving No. 10 lymph node dissection for advanced proximal gastric
      cancer using a left-sided approach is technically feasible. It simplifies the
      complicated surgical procedure of No. 10 lymph node dissection and leads to the
      popularization and promotion of this technique.

PMID- 23146049
TI  - T-cell therapy: a powerful tool for the management of viral infections and
      relapse post hematopoietic stem cell transplantation.

PMID- 23146048
TI  - Triclosan exposure and allergic sensitization in Norwegian children.
AB  - BACKGROUND: Exposure to the synthetic antimicrobial chemical, triclosan, used in
      personal care products, has been hypothesized to lead to allergic disease. We
      investigated whether triclosan exposure was associated with allergic
      sensitization and symptoms in 10-year-old Norwegian children. METHODS: Urinary
      concentrations of triclosan were measured in one first morning void from 623
      children, collected during 2001-2004. Logistic regression models, controlling for
      urine specific gravity, parental allergic disease, maternal education, and
      household income, were fitted for allergic sensitization (either skin prick test
      positivity or serum-specific IgE >= 0.35 kU/l to at least one of 15 evaluated
      inhalant and food allergens), current rhinitis, and current asthma (questionnaire
      and exercise challenge test). RESULTS: The adjusted odds ratio (aOR) for allergic
      sensitization among those in the fourth quartile of triclosan concentration was
      2.0 [95% confidence interval (CI): 1.1, 3.4] compared with the reference group
      (<the limit of detection), and the aOR per log(10)  unit increase in triclosan
      was 1.2 (95% CI: 1.0, 1.4). The aOR for current rhinitis was 1.9 (95% CI: 1.1,
      3.4) for the fourth quartile and 1.2 (95% CI: 0.97, 1.4) per log(10)  unit
      increase in triclosan. CONCLUSION: Triclosan concentrations were associated with
      allergic sensitization, especially inhalant and seasonal allergens, rather than
      food allergens. Current rhinitis was associated with the highest levels of
      triclosan, whereas no association was seen for current asthma. These results are
      consistent with recent findings in other studies and provide additional evidence
      for an association between triclosan and allergy.

PMID- 23146052
TI  - The emerging role of PET in Hodgkin lymphoma patients receiving autologous stem
      cell transplant.
AB  - High-dose chemotherapy followed by autologous stem cell transplant (ASCT) is the
      standard therapy for patients with relapsed or refractory Hodgkin lymphoma.
      Several analyses have reported risk factors for a poor outcome after ASCT to
      allow for an individualized treatment, but there is no consensus on how the
      outcome in high-risk patients might be improved. A recent study by Cocorocchio et
      al. analyzes risk factors in 97 patients who received ASCT. Besides the
      established risk factor remission status after induction, result of positron
      emission tomography before and after transplant was the most important prognostic
      factor for progression-free survival and overall survival. This result is in line
      with other retrospective analyses and might allow for the selection of high-risk
      patients who should receive alternative treatment approaches, such as second-line
      salvage therapy, tandem ASCT, new drugs or maintenance therapy. Randomized trials
      characterizing the best therapeutic option for high-risk patients are highly
      warranted.

PMID- 23146050
TI  - Complementary combinations: what treatments will become key to the battle against
      acute myelogenous leukemia?

PMID- 23146053
TI  - Understanding the genetic basis of Glanzmann thrombasthenia: implications for
      treatment.
AB  - Glanzmann thrombasthenia (GT) is characterized by mucocutaneous bleeding due to
      platelets that fail to aggregate in response to physiologic stimuli. GT, a rare
      inherited disease, is caused by quantitative or qualitative deficiencies of
      alphaIIbbeta3, an integrin receptor for adhesive proteins. Coded by the ITGA2B
      and ITGB3 genes, alphaIIbbeta3 mediates platelet-to-platelet attachment,
      aggregation and clot retraction. Despite widespread mutation analysis, the reason
      for the extensive variation in both the severity and intensity of bleeding among
      affected individuals remains poorly understood. Although genetic defects of ITGB3
      affect other tissues where beta3 is present as alphavbeta3 (the vitronectin
      receptor), the bleeding phenotype continues to dominate. The authors now examine
      the relationship between genotype and phenotype in classic and variant forms of
      GT, and reassess if the nature of the gene mutation influences bleeding and
      treatment aimed at restoring hemostasis.

PMID- 23146054
TI  - Hypercoagulability in beta-thalassemia: a status quo.
AB  - Life expectancy of thalassemia patients has markedly improved over the last few
      decades, but patients still suffer from many complications of their congenital
      chronic disease, and several new complications are now being acknowledged,
      including thrombosis. The high prevalence of thromboembolic events, especially in
      thalassemia intermedia, has led to the identification of a hypercoagulable state
      in these patients. This review summarizes current knowledge of the clinical and
      pathophysiological characteristics of hypercoagulability in thalassemia patients.
      Strategies to prevent thrombotic events are also discussed.

PMID- 23146055
TI  - Current clinical management of Fanconi anemia.
AB  - Fanconi anemia (FA) is a heterogeneous disease characterized by spontaneous
      chromosomal breaks and abnormal DNA repair. Major clinical problems in FA include
      congenital abnormalities, endocrinopathies, early onset bone marrow failure and
      increased risk of myelodysplastic syndrome, acute leukemia and solid tumors. To
      date, 15 different genes have been shown to cause FA, all of which have some role
      in DNA double-strand break repair. Very few strict genotype-phenotype
      associations have been identified and clinical manifestations vary widely from
      patient to patient, most likely due to modifier genes, environment and chance
      effects. Hematopoietic stem cell transplantation is the only proven cure for the
      hematopoietic manifestations of FA and aggressive lifelong surveillance for solid
      tumors is essential.

PMID- 23146056
TI  - Erythrocyte morphology in metabolic syndrome.
AB  - The study of erythrocyte morphology is of great importance in the field of
      hemorheology as the deformability of the circulating cells has a fundamental
      influence on the rheological properties of the blood. Diabetes mellitus,
      hypertension, dyslipidemia and obesity (mostly central obesity) are the major
      components of metabolic syndrome. In this review, we focus on the changes in
      erythrocyte morphology in different components of metabolic syndrome and also
      discuss the erythrocyte morphology in regards to oxidative stress - a common
      state of chronic diseases. This article also addresses the problem of
      inconsistency in the use of nomenclature and technique to identify the abnormal
      morphology and we recommend the use of standard terminology by all authors.

PMID- 23146057
TI  - Sequential or combination therapy for multiple myeloma.
AB  - In myeloma management, whether to offer sequential or combination therapies has
      largely remained elusive, partly for the reason that there are no conclusive
      studies evaluating this question and partly owing to the paradigm shift in
      myeloma outcomes over the last decade raising the same question again, but now in
      a different context with active agents such as immunomodulatory drugs and
      proteasome inhibitors being available. Historically, in myeloma, combination
      cytotoxic chemotherapy compared with the standard-of-care melphalan and
      prednisone regimen resulted in similar response rates, raising the question of
      efficacy of the cytotoxic combination therapies with high toxicities and the
      preference for sequential therapies in order to lower the toxicity of the chosen
      treatment. However, with the use of more active novel agents with favorable
      toxicity profiles such as bortezomib, thalidomide and lenalidomide, re-evaluation
      of this question is necessary.

PMID- 23146059
TI  - Intrauterine growth and childhood leukemia and lymphoma risk.
AB  - Leukemias and lymphomas account for nearly half of all childhood cancers.
      Although there have been major advances in the treatment of these diseases, what
      causes them remains largely unknown. There is strong evidence to suggest that
      leukemia originates in utero, and early life factors may play a role in its
      etiology. A series of reports illustrate a convincing link between the rate of
      intrauterine growth and the risk of childhood leukemia. Some studies suggest that
      this risk relationship also extends to non-Hodgkin lymphoma in children,
      although, overall, the association with childhood lymphoma is less clear. This
      review discusses the intricacies of these risk relationships and explores
      potential explanations of how the rate of fetal growth may influence cancer risk.

PMID- 23146058
TI  - Molecular prognostic factors in cytogenetically normal acute myeloid leukemia.
AB  - Chromosomal abnormalities are detected in 50-60% of patients with acute myeloid
      leukemia (AML) and are important predictors of prognosis and risk of relapse. The
      remaining patients, those with cytogenetically normal AML, are a seemingly
      homogeneous group that in fact consists of subsets of patients with distinct
      clinical outcomes. This heterogeneity is likely related to acquired gene
      mutations, as well as altered miRNA and gene-expression profiles, which occur
      within the group. The identification of recurrent molecular abnormalities has
      improved prognostication and provided insight into mechanisms of leukemogenesis
      for patients with cytogenetically normal AML, as well as led to the discovery of
      novel therapeutic targets. As the number of mutations continues to expand,
      bioinformatic algorithms that allow for integration of multiple markers will be
      necessary to provide optimal care for patients with this disease.

PMID- 23146062
TI  - Should nicorandil infusion be adapted in dialysis-dependent patients undergoing
      continuous renal replacement therapy after cardiac surgery?
AB  - In this report, we studied whether plasma concentration of nicorandil is
      maintained effectively and safely in dialysis-dependent patients with stage 5
      chronic kidney disease (CKD5D) undergoing continuous renal replacement therapy
      (CRRT). Participants consisted of 10 patients undergoing CRRT after cardiac
      surgery. CRRT was performed with an effluent flow rate of either 600 mL/h (low
      flow group; n = 5) or 1800 mL/h (high-flow group; n = 5). Nicorandil was infused
      intravenously at 0.1 mg/kg/h for more than 15 h starting 8 h before and 7 h after
      the start of CRRT. Plasma nicorandil concentrations were measured from arterial
      blood lines 1 h before and 7 h after CRRT initiation. Nicorandil clearance by
      CRRT was also calculated 1 h after CRRT initiation. Nicorandil plasma
      concentrations before and 7 h after CRRT initiation were 68.0 ng/mL and 74.6
      ng/mL, respectively. Nicorandil clearance 1 h after CRRT initiation was 20.2
      mL/min. Increasing the effluent flow rate from 600 mL/h to 1800 mL/h tended to
      increase nicorandil clearance. When nicorandil was infused intravenously during
      CRRT at 0.1 mg/kg/h in patients with CKD5D, plasma nicorandil concentrations were
      maintained within an effective concentration range.

PMID- 23146061
TI  - A yeast tRNA mutant that causes pseudohyphal growth exhibits reduced rates of CAG
      codon translation.
AB  - In Saccharomyces cerevisiae, the SUP70 gene encodes the CAG-decoding
      tRNA(Gln)(CUG). A mutant allele, sup70-65, induces pseudohyphal growth on rich
      medium, an inappropriate nitrogen starvation response. This mutant tRNA is also a
      UAG nonsense suppressor via first base wobble. To investigate the basis of the
      pseudohyphal phenotype, 10 novel sup70 UAG suppressor alleles were identified,
      defining positions in the tRNA(Gln)(CUG) anticodon stem that restrict first base
      wobble. However, none conferred pseudohyphal growth, showing altered CUG
      anticodon presentation cannot itself induce pseudohyphal growth. Northern blot
      analysis revealed the sup70-65 tRNA(Gln)(CUG) is unstable, inefficiently charged,
      and 80% reduced in its effective concentration. A stochastic model simulation of
      translation predicted compromised expression of CAG-rich ORFs in the
      tRNA(Gln)(CUG)-depleted sup70-65 mutant. This prediction was validated by
      demonstrating that luciferase expression in the mutant was 60% reduced by
      introducing multiple tandem CAG (but not CAA) codons into this ORF. In addition,
      the sup70-65 pseudohyphal phenotype was partly complemented by overexpressing CAA
      decoding tRNA(Gln)(UUG), an inefficient wobble-decoder of CAG. We thus show that
      introducing codons decoded by a rare tRNA near the 5' end of an ORF can reduce
      eukaryote translational expression, and that the mutant tRNA(CUG)(Gln)
      constitutive pseudohyphal differentiation phenotype correlates strongly with
      reduced CAG decoding efficiency.

PMID- 23146063
TI  - European guidelines for diagnosis and treatment of adenovirus infection in
      leukemia and stem cell transplantation: summary of ECIL-4 (2011).
AB  - Human adenovirus (HAdV) infections are increasingly recognized as important
      pathogens in immunocompromised hosts, especially in patients with severely
      suppressed T-cell function. The 4th European Conference of Infections in Leukemia
      (ECIL-4) has developed evidence-based guidelines for diagnosis and management of
      HAdV infections. The risk for HAdV-associated disease is increased in children,
      and risk factors for HAdV disease are T-cell depletion, unrelated and cord blood
      hematopoietic stem cell transplantation, graft-versus-host disease grades III-IV,
      and lymphopenia. The recommended technique for monitoring of high-risk patients
      is quantitative polymerase chain reaction. Cidofovir is the most used antiviral
      therapy, although no controlled study has been performed. HAdV-specific T-cell
      therapy is in development.

PMID- 23146064
TI  - Governance of innovation and appropriateness of hospitalization for high-risk
      pregnancy: the TOCOMAT system.
AB  - BACKGROUND: Over the last 30 years, a great increase in the application of
      technologies in public health, with an undisputed impact on both the
      effectiveness of performance and the investment and management costs, has
      occurred. This evidence has induced the development of assessment tools to
      clarify the relationships among resources, outputs, and outcomes of technological
      innovations. This analysis was developed in order to examine the use of a
      telematic system for reporting remotely transmitted cardiotocographic traces,
      specifically (1) its impact on the health organization and on the appropriateness
      of the care setting used and (2) the efficiency of its adoption in a regional
      network. MATERIALS AND METHODS: We adopted a case-control study on patients'
      medical records during the first 4 months of 2009, 2010, and 2011 and a cost
      analysis of resources used for the creation of a computerized
      telecardiotocography network connecting eight peripheral areas to the operations
      center. RESULTS: The case-control study showed a reduction in the average
      hospital stay days for high-risk patients (1.32) and for low-risk patient (1.7)
      with a total of cost savings of ?89,628 for high-risk patients and ?170,170 for
      low-risk patients. The cost savings of the regional network was ?20,769.04.
      CONCLUSIONS: The adoption of a remote transmission system of cardiotocography
      provided a managerial and economic advantage in the reduction of inappropriate
      admissions for prepartum symptoms and an improvement in the admission indicators
      (hospital stay days).

PMID- 23146065
TI  - Pilot study of topical acetyl hexapeptide-8 in the treatment for blepharospasm in
      patients receiving botulinum toxin therapy.
AB  - BACKGROUND AND PURPOSE: Injectable botulinum neurotoxin (BoNT) is the principal
      effective treatment for blepharospasm (BSP). This trial explores the safety and
      efficacy of topical acetyl hexapeptide-8 (AH8), a competitive SNAP25 inhibitor,
      as a potential new therapy in BSP. METHODS: Double-blind, placebo-controlled,
      randomized trial of daily topical application of AH8 in 24 patients with BSP. The
      primary outcome was time to return to baseline Jankovic Blepharospasm Rating
      Scale (JBRS) after a BoNT injection simultaneously with the initiation of AH8.
      Patients displaying a strictly regular pattern of response to 3-monthly
      injections of BoNT were included. RESULTS: There were no significant adverse
      events. There was a trend for longer time until return to baseline JBRS after
      injection in the active group compared to placebo (3.7 months vs. 3.0 months),
      and for better scores in the active group. One-third (4/12) of the patients in
      the active group had a considerable extension of symptom control after BoNT
      (range: 3.3-7.1 months). CONCLUSIONS: Topical AH8 is safe and promising for
      extending the duration of action of BoNT therapy for BSP.

PMID- 23146066
TI  - Effects of 5',8-cyclodeoxyadenosine triphosphates on DNA synthesis.
AB  - Hydroxyl radicals generate a broad range of DNA lesions in living cells.
      Cyclopurine deoxynucleosides (CPUs) are a biologically significant class of
      oxidative DNA lesions due to their helical distortion and chemically stability.
      The CPUs on DNA are substrates for the nucleotide excision repair (NER) but not
      for base excision repair or direct damage reversal. Moreover, these lesions block
      DNA and RNA polymerases, resulting in cell death. Here, we describe the chemical
      synthesis of 5'S and 5'R isomers of 5',8-cyclodeoxyadenosine triphosphate (cdATP)
      and demonstrate their ability to be incorporated into DNA by replicative DNA
      polymerases. DNA synthesis assays revealed that the incorporation of the
      stereoisomeric cdATPs strongly inhibits DNA polymerase reactions. Surprisingly,
      the two stereoisomers had different mutagenic profiles, since the S isomer of
      cdATP could be inserted opposite to the dTMP, but the R isomer of cdATP could be
      inserted opposite to the dCMP. Kinetic analysis revealed that the S isomer of
      cdATP could be incorporated more efficiently (25.6 MUM(-1) min(-1)) than the R
      isomer (1.13 MUM(-1) min(-1)) during DNA synthesis. Previous data showed that the
      S isomer in DNA blocked DNA synthesis and the exonuclease activity of DNA
      polymerase and is less efficiently repaired by NER. This indicates that the S
      isomer has a tendency to accumulate on the genome DNA, and as such, the S isomer
      of cdATP may be a candidate cytotoxic drug.

PMID- 23146068
TI  - Mechanisms and functional consequences of liver failure substantially differ
      between endotoxaemia and faecal peritonitis in rats.
AB  - BACKGROUND: Many of the concepts describing molecular mechanisms of sepsis
      induced liver failure are derived from endotoxin models. However, the biological
      significance of such models is questionable as the complexity of clinical sepsis
      and associated organ failure is only partially replicated. AIMS: Comparison of
      cytokine response, leucocyte recruitment, oxidative stress and markers of hepatic
      organ dysfunction in rat models of endotoxaemia or peritoneal contamination and
      infection (PCI). METHODS: Endotoxemia and polymicrobial sepsis were induced in
      rats by intraperitoneal injection of lipopolysaccharide (LPS) or stool
      suspension, respectively. RESULTS: Both insults produced clinical and laboratory
      signs of multiple organ dysfunction, including hepatic excretory dysfunction.
      However, TNF alpha, oxidative stress responses and the degree of cell death were
      significantly higher in endotoxaemia compared to PCI (e.g. serum TNF levels
      (pg/ml) at 1.5 h post-insult: sham 5 +/- 1.4, LPS 1 mg/kg bw 2176.92 +/- 373.78,
      sepsis below detection limit; P P < 0.05). Cholestasis was significantly more
      pronounced in polymicrobial sepsis whereas serum bilirubin in endotoxaemic
      animals did not differ from sham-operated controls (plasma levels of bilirubin
      (MUmol/L) at 15 h after the insult: sham 7.1 +/- 0.6, LPS 30 mg/kg 9.1 +/- 0.6,
      sepsis 15.2 +/- 1.3). CONCLUSIONS: Polymicrobial sepsis produces profound
      hepatocellular dysfunction in the absence of traditional cytokine-mediated
      mechanisms of cellular injury. This questions the central role of cytokines and
      the ensuing oxidative stress as key molecular events in mediating liver
      dysfunction.

PMID- 23146069
TI  - The important but underappreciated transgastric right ventricular inflow view for
      transesophageal echocardiographic evaluation of cardiac implantable device
      infections.
AB  - Device infection is a potential complication of cardiovascular implantable
      electronic devices. We report a case of a 40-year-old man with nonischemic
      cardiomyopathy, status post biventricular implantable cardiac defilbrillator
      placement on continuous home dobutamine, who presented with methicillin-resistant
      Staphylococcus aureus bacteremia. Transesophageal echocardiography showed a 2.4
      cm vegetation near the right ventricular (RV) apex that was only seen in the
      transgastric RV inflow view. This case demonstrates an atypical distal location
      for a vegetation and illustrates the importance of obtaining multiple views,
      including the transgastric RV inflow view, when evaluating for device wire
      vegetations.

PMID- 23146070
TI  - 1,2-Dibromotetrachloroethane: an ozone-friendly reagent for the in situ Ramberg
      Backlund rearrangement and its use in the formal synthesis of E-resveratrol.
AB  - Dibromotetrachloroethane (C(2)Br(2)Cl(4)) is demonstrated as a halogenating
      reagent for the one-pot conversion of sulfones to alkenes by way of the Ramberg
      Backlund rearrangement. Dibromotetrachloroethane successfully replaces known
      ozone depleting agents CCl(4), CBr(2)F(2) and C(2)Br(2)F(4). A formal synthesis
      of E-resveratrol is demonstrated using C(2)Br(2)Cl(4).

PMID- 23146071
TI  - Home-based HIV counseling and testing: client experiences and perceptions in
      Eastern Uganda.
AB  - BACKGROUND: Though prevention and treatment depend on individuals knowing their
      HIV status, the uptake of testing remains low in Sub-Saharan Africa. One
      initiative to encourage HIV testing involves delivering services at home.
      However, doubts have been cast about the ability of Home-Based HIV Counseling and
      Testing (HBHCT) to adhere to ethical practices including consent,
      confidentiality, and access to HIV care post-test. This study explored client
      experiences in relation these ethical issues. METHODS: We conducted 395
      individual interviews in Kumi district, Uganda, where teams providing HBHCT had
      visited 6-12 months prior to the interviews. Semi-structured questionnaires
      elicited information on clients' experiences, from initial community mobilization
      up to receipt of results and access to HIV services post-test. RESULTS: We found
      that 95% of our respondents had ever tested (average for Uganda was 38%). Among
      those who were approached by HBHCT providers, 98% were informed of their right to
      decline HIV testing. Most respondents were counseled individually, but 69% of the
      married/cohabiting were counseled as couples. The majority of respondents (94%)
      were satisfied with the information given to them and the interaction with the
      HBHCT providers. Most respondents considered their own homes as more private than
      health facilities. Twelve respondents reported that they tested positive, 11 were
      referred for follow-up care, seven actually went for care, and only 5 knew their
      CD4 counts. All HIV infected individuals who were married or cohabiting had
      disclosed their status to their partners. CONCLUSION: These findings show a very
      high uptake of HIV testing and satisfaction with HBHCT, a large proportion of
      married respondents tested as couples, and high disclosure rates. HBHCT can play
      a major role in expanding access to testing and overcoming disclosure challenges.
      However, access to HIV services post-test may require attention.

PMID- 23146072
TI  - Tuning the electro-optical properties of germanium nanowires by tensile strain.
AB  - In this Letter we present the electrical and electro-optical characterization of
      single crystalline germanium nanowires (NWs) under tensile strain conditions. The
      measurements were performed on vapor-liquid-solid (VLS) grown germanium (Ge) NWs,
      monolithically integrated into a micromechanical 3-point strain module. Uniaxial
      stress is applied along the ?111? growth direction of individual, 100 nm thick Ge
      NWs while at the same time performing electrical and optical characterization at
      room temperature. Compared to bulk germanium, an anomalously high and negative
      signed piezoresistive coefficient has been found. Spectrally resolved
      photocurrent characterization on strained NWs gives experimental evidence on the
      strain-induced modifications of the band structure. Particularly we are revealing
      a rapid decrease in resistivity and a red-shift in photocurrent spectra under
      high strain conditions. For a tensile strain of 1.8%, resistivity decreased by a
      factor of 30, and the photocurrent spectra shifted by 88 meV. Individual stressed
      NWs are recognized as an ideal platform for the exploration of strain-related
      electronic and optical effects and may contribute significantly to the
      realization of novel optoelectronic devices, strain-enhanced field-effect
      transistors (FETs), or highly sensitive strain gauges.

PMID- 23146073
TI  - Regulation of mercaptopyruvate sulfurtransferase activity via intrasubunit and
      intersubunit redox-sensing switches.
AB  - SIGNIFICANCE: Redox regulates 3-mercaptopyruvate sulfurtransferase (MST, EC
      2.8.1.2) activity via both intermolecular and intramolecular redox-sensing
      switches. The intermolecular switch comprises an intermolecular disulfide bond
      that forms a homodimer. On the other hand, the intramolecular switch is a
      catalytic site cysteine that forms a low redox potential sulfenate. Both switches
      are reduced by thioredoxin with the reducing system, including thioredoxin
      reductase and NADPH, and to a much lesser extent by reduced glutathione. It
      becomes clear that MST serves as not only an enzyme in cysteine catabolism, but
      also as an antioxidant protein. RECENT ADVANCES: New findings have been
      accumulated that, in the catalytic process of MST, hydrogen peroxide is possibly
      produced by persulfide of the sulfur-accepted substrate and sulfur oxides are
      possibly produced in the redox cycle of persulfide formed at the catalytic site
      cysteine of the reaction intermediate. Further, we recently succeeded to produce
      MST knockout (KO) mice. CRITICAL ISSUES: A congenital metabolic disorder,
      mercaptolactate-cysteine disulfiduria (MCDU) is caused by MST defect with or
      without mental retardation. The MST KO mouse is just a MCDU model. Recent
      findings suggest that hydrogen sulfide and/or sulfur oxides are involved in the
      neurobehavioral changes in MCDU. FUTURE DIRECTIONS: We investigate the
      pathogenesis of MCDU by performing a comprehensive analysis of the MST KO mice to
      clarify the functional diversity of MST and biological importance of hydrogen
      sulfide and sulfur oxides in the brain.

PMID- 23146074
TI  - The carpal pad as an alternative sampling site for blood glucose testing in dogs.
AB  - OBJECTIVE: To investigate the feasibility and validity of sampling blood from the
      carpal pad in hospitalised healthy and diabetic dogs. METHODS: The carpal pad was
      compared to the ear as a sampling site in 60 dogs (30 healthy and 30 diabetic
      dogs). RESULTS: Lancing the pads was very well tolerated. The average glucose
      concentrations in blood samples obtained from the ears and carpal pads exhibited
      a strong positive correlation (r = 0.938) and there were no significant
      differences between them (P = 0.914). In addition, 98.3% of the values obtained
      were clinically acceptable when assessed by the error grid analysis. CLINICAL
      SIGNIFICANCE: The carpal pad is a good alternative sampling site for home
      monitoring, especially in animals with a soft and/or light-coloured pad.

PMID- 23146075
TI  - Palladium-catalyzed intermolecular C3 alkenylation of indoles using oxygen as the
      oxidant.
AB  - A general and efficient palladium-catalyzed intermolecular direct C3 alkenylation
      of indoles using oxygen as the oxidant has been developed. The reaction is of
      complete regio- and stereoselectivity. All products are E-isomers at the C3
      position, and no Z-isomers or 2-substituted product can be detected.

PMID- 23146076
TI  - A new species of monorchiid (Digenea) from the South China Sea.
AB  - A new species of monorchiid trematode, Leiomonorchis zhanjiangensis n. sp.
      (Trematoda: Monorchiidae), is described from the intestine of marine fish Secutor
      ruconius (Hamilton-Buchanan) (Leiognathidae) from Zhanjiang (21 degrees 2'N, 110
      degrees 3'E), Guangdong Province, China. The new species is distinguished from
      all known species of the genus, mainly by the configuration of vitelline
      follicles and the shape of excretory bladder (saccular in the new species vs.
      tubular in the others). According to Madhavi's opinion, Caballerotrematoides
      secundus Ahmad, 1981 was transferred from Caballerotrematoides Madhavi, 1977 into
      Leiomonorchis Mamaev, 1970 as L. secundus (Ahmad, 1981) n. comb.

PMID- 23146077
TI  - Role of distance-learning modules and contact sessions in developing knowledge
      and skills of junior doctors for practicing effectively in rural hospitals in
      India.

PMID- 23146067
TI  - Antidepressant therapy in epilepsy: can treating the comorbidities affect the
      underlying disorder?
AB  - There is a high incidence of psychiatric comorbidity in people with epilepsy
      (PWE), particularly depression. The manifold adverse consequences of comorbid
      depression have been more clearly mapped in recent years. Accordingly,
      considerable efforts have been made to improve detection and diagnosis, with the
      result that many PWE are treated with antidepressant drugs, medications with the
      potential to influence both epilepsy and depression. Exposure to older
      generations of antidepressants (notably tricyclic antidepressants and bupropion)
      can increase seizure frequency. However, a growing body of evidence suggests that
      newer ('second generation') antidepressants, such as selective serotonin reuptake
      inhibitors or serotonin-noradrenaline reuptake inhibitors, have markedly less
      effect on excitability and may lead to improvements in epilepsy severity.
      Although a great deal is known about how antidepressants affect excitability on
      short time scales in experimental models, little is known about the effects of
      chronic antidepressant exposure on the underlying processes subsumed under the
      term 'epileptogenesis': the progressive neurobiological processes by which the
      non-epileptic brain changes so that it generates spontaneous, recurrent seizures.
      This paper reviews the literature concerning the influences of antidepressants in
      PWE and in animal models. The second section describes neurobiological mechanisms
      implicated in both antidepressant actions and in epileptogenesis, highlighting
      potential substrates that may mediate any effects of antidepressants on the
      development and progression of epilepsy. Although much indirect evidence suggests
      the overall clinical effects of antidepressants on epilepsy itself are
      beneficial, there are reasons for caution and the need for further research,
      discussed in the concluding section.

PMID- 23146078
TI  - Academic dishonesty and ethical reasoning: pharmacy and medical school students
      in New Zealand.
AB  - BACKGROUND: There is ample evidence to suggest that academic dishonesty remains
      an area of concern and interest for academic and professional bodies. There is
      also burgeoning research in the area of moral reasoning and its relevance to the
      teaching of pharmacy and medicine. AIMS: To explore the associations between self
      reported incidence of academic dishonesty and ethical reasoning in a professional
      student body. METHODS: Responses were elicited from 433 pharmacy and medicine
      students. A questionnaire eliciting responses about academic dishonesty (copying,
      cheating, and collusion) and their decisions regarding an ethical dilemma was
      distributed. Multivariate analysis procedures were conducted. RESULTS: The
      findings suggested that copying and collusion may be linked to the way students
      make ethical decisions. Students more likely to suggest unlawful solutions to the
      ethical dilemma were more likely to disclose engagement in copying information
      and colluding with other students. CONCLUSIONS: These findings imply that
      students engaging in academic dishonesty may be using different ethical
      frameworks. Therefore, employing ethical dilemmas would likely create a useful
      learning framework for identifying students employing dishonest strategies when
      coping with their studies. Increasing understanding through dialog about
      engagement in academic honesty will likely construct positive learning outcomes
      in the university with implications for future practice.

PMID- 23146079
TI  - Diastolic timed Vibro-Percussion at 50 Hz delivered across a chest wall sized
      meat barrier enhances clot dissolution and remotely administered Streptokinase
      effectiveness in an in-vitro model of acute coronary thrombosis.
AB  - BACKGROUND: Low Frequency Vibro-Percussion (LFVP) assists clearance of thrombi
      in catheter systems and when applied to the heart and timed to diastole is known
      to enhance coronary flow. However LFVP on a clotted coronary like vessel given
      engagement over a chest wall sized barrier (to resemble non-invasive heart attack
      therapy) requires study. METHODS: One hour old clots (n=16) were dispensed within
      a flexible segment of Soft-Flo catheter (4 mm lumen), weighted, interfaced with
      Heparinized Saline (HS), secured atop a curved dampening base, and photographed.
      A ~4 cm meat slab was placed over the segment and randomized to receive
      intermittent LFVP (engaged, - disengaged at 1 second intervals), or no LFVP for
      20 minutes. HS was pulsed (~120/80 mmHg), with the diastolic phase coordinated to
      match LFVP delivery. The segment was then re-photographed and aspirated of fluid
      to determine post clot weight. The trial was then repeated with 0.5 mls of
      Streptokinase (15,000 IU/100 microlitre) delivered ~ 2 cm upstream from the clot.
      RESULTS: LFVP - HS only samples (vs. controls) showed; a) development of clot
      length fluid channels absent in the control group (p < 0.0002); b) enhanced
      dissolved clot mixing scores ( 5.0 vs. 0.8, p < 2.8 E - 6); and c) increased
      percent clot dissolution (23.0% vs. 1.8% respectively, p < 8.5 E-6). LFVP - SK
      samples had a similar comparative clot disruptive profile, however fluid channels
      developed faster and percent clot dissolution more than doubled (51.0% vs. 3.0%,
      p< 9.8 E- 6). CONCLUSION: Diastolic timed LFVP (50 Hz) engaged across a chest
      wall sized barrier enhances clot disruptive effects to an underlying coronary
      like system.

PMID- 23146080
TI  - Selective suture ligation of the dorsal vein complex during robot-assisted
      laparoscopic radical prostatectomy.
AB  - Technique for apical dissection and control of the dorsal vein complex (DVC)
      during robot-assisted laparoscopic radical prostatectomy (RALP) affects blood
      loss, apical positive margins, and recovery of urinary control. Over the past 7
      years, our technique for apical dissection has been spurred by the overarching
      goal of minimizing injury to the rhabdosphincter to improve urinary continence,
      evolving from stapling to suture ligation of the DVC before bladder neck
      dissection to an athermal DVC division followed by selective suture ligation (DVC
      SSL) before RALP anastomosis. Assessment of patient-reported quality of life
      outcomes demonstrates earlier recovery of continence with DVC-SSL.

PMID- 23146081
TI  - Molecularly resolved images of peptide-functionalized gold surfaces by scanning
      tunneling microscopy.
AB  - Peptide-terminated monolayers were formed through a Huisgen cycloaddition
      reaction between an alpha-helical peptide containing two propargylglycine
      unnatural functional groups 20 A apart and an alkanethiol self-assembled
      monolayer (SAM) on a gold surface containing 25% surface density of reactive
      azide terminal groups. The azide- and peptide-terminated surfaces were imaged by
      scanning tunneling microscopy (STM) using a low tunneling current of 10 pA. On
      the peptide-terminated surface, oblong features ~30 A long and ~20 A wide were
      observed and attributed to individual surface-bound alpha-helical peptides
      oriented parallel to the gold surface. These features covered an area of the
      surface corresponding to a density of 0.11 +/- 0.01 peptides nm(-2), compared
      with a theoretical density of ~0.14 peptides nm(-2) for a fully reacted surface.
      Finally, no evidence of peptide aggregation was observed on either short (<10 nm)
      or long (~100 nm) length scales.

PMID- 23146083
TI  - Occurrence of CCSVI in patients with MS and its relationship with iron metabolism
      and varicose veins.
AB  - BACKGROUND AND PURPOSE: A new treatable venous disorder, chronic cerebrospinal
      venous insufficiency (CCSVI), has been proposed in patients with multiple
      sclerosis (MS). Its relationship with iron metabolism is suggested, but has not
      been examined prospectively. METHODS: We performed extra- and transcranial echo
      colour Doppler (ECD) in 90 patients with MS and 41 healthy controls (HC). Indices
      of iron metabolism and the presence of peripheral signs of impaired venous flow
      were also examined. RESULTS: The ECD examination showed CCSVI in 8 (9%) of the 90
      patients with MS and 0 HC (P = 0.11). The 8 CCSVI-positive MS patients were older
      (P = 0.02), had less often relapsing-remitting-MS (P = 0.02) and had more
      neurological disability assessed by expanded disability status scale (EDSS, P =
      0.001) and longer duration of disease (P = 0.02) in comparison with the 82 CCSVI
      negative MS patients. Multivariate analysis revealed that EDSS remained an
      independent factor associated with CCSVI (odds ratio 1.89, 95%CI 1.17-3.05, P
      value = 0.009). CCSVI MS patients more often had bilateral telangiectasia at the
      legs (P = 0.008), reticular veins (P = 0.006) and venous stasis dermatitis (P =
      0.004). No relationship was found between CCSVI and impaired iron metabolism in
      patients with MS. CONCLUSIONS: CCSVI is uncommon and is a secondary epiphenomenon
      in MS and related to more neurological disability and the presence of varicose
      veins at the legs.

PMID- 23146082
TI  - Role of immediate radical cystectomy in the treatment of patients with residual
      T1 bladder cancer on restaging transurethral resection.
AB  - WHAT'S KNOWN ON THE SUBJECT? AND WHAT DOES THE STUDY ADD?: Bladder cancer
      patients with lamina propria invasion (T1 disease) and residual T1 disease on
      restaging transurethral resection of bladder tumour (re-TURBT) are at a very high
      risk for recurrence and progression. Despite this risk, most patients are treated
      with a bladder preserving approach and not immediate radical cystectomy (RC). In
      this study we have shown that a quarter of patients with T1 bladder cancer and
      residual T1 on re-TURBT who are treated with immediate RC are found to have
      carcinoma invading bladder muscle at RC and 5% have lymph node metastases. We
      have also found that >30% of patients treated with deferred RC after initial
      bladder-preserving therapy harbour carcinoma invading bladder muscle and almost
      20% of these patients have lymph node metastases. Thus, immediate RC should be
      considered in all patients with T1 bladder cancer and residual T1 on re-TURBT.
      OBJECTIVE: To report the overall survival (OS) and cancer-specific survival (CSS)
      of patients with residual T1 bladder cancer on restaging transurethral resection
      of the bladder tumour (re-TURBT). MATERIALS AND METHODS: We performed a
      retrospective review of 150 evaluable patients treated for T1 bladder cancer with
      residual T1 disease found on re-TURBT between 1990 and 2007. Patients were
      treated with immediate radical cystectomy (RC) or a bladder-preserving approach
      (deferred or no RC). A univariate Cox proportional hazards regression model was
      used to test the association between treatment approach and survival. RESULTS:
      Residual T1 bladder cancer was found in 150 evaluable patients, of whom 57
      received immediate RC and 93 were treated with a bladder-preserving approach.
      Fourteen out of 57 patients receiving immediate RC and 8/26 patients receiving
      deferred RC had carcinoma invading bladder muscle in the RC specimen. Three out
      of 57 and 5/26 patients had lymph node metastases in the RC specimen. Median
      follow-up was 3.74 years. Thirty-nine patients died during follow-up, 16 from
      bladder cancer. There was no significant association between immediate RC and CSS
      (hazard ratio [HR] 1.15, 95% confidence interval [CI] 0.43-3.09, P = 0.8) or OS
      (HR 0.79, 95% CI 0.4-1.53, P = 0.5). CONCLUSIONS: Because of the low number of
      events we cannot conclude whether RC offers a survival advantage in patients with
      residual T1 bladder cancer on re-TURBT. Since a quarter of patients had carcinoma
      invading bladder muscle, RC should be considered in these patients. A larger,
      preferably randomized, study with longer follow-up is needed.

PMID- 23146086
TI  - Pharmacokinetics of tolfenamic acid following two oral dose levels in buffalo
      calves.

PMID- 23146087
TI  - Multimodality imaging of mitral perivalvular abscess with annular fistula and
      preserved leaflet function.
AB  - A devastating complication of both native and prosthetic valvular infective
      endocarditis can involve periannular extension, which is associated with
      increased perioperative mortality and long-term adverse outcomes. Cardiac
      imaging, both noninvasive and invasive, is essential to accurately identify the
      extent and complexity of these infections to perform effective surgical
      interventional strategies. We present the case of a 62-year-old woman who was
      found to have a perivalvular mitral valve abscess with an annular fistula without
      evidence of mitral valve leaflet involvement on histopathology, diagnosed by 3
      dimensional transesophageal echocardiography, computed tomography, and left
      ventriculography.

PMID- 23146088
TI  - Automation of the CHARMM General Force Field (CGenFF) I: bond perception and atom
      typing.
AB  - Molecular mechanics force fields are widely used in computer-aided drug design
      for the study of drug-like molecules alone or interacting with biological
      systems. In simulations involving biological macromolecules, the biological part
      is typically represented by a specialized biomolecular force field, while the
      drug is represented by a matching general (organic) force field. In order to
      apply these general force fields to an arbitrary drug-like molecule,
      functionality for assignment of atom types, parameters, and charges is required.
      In the present article, which is part I of a series of two, we present the
      algorithms for bond perception and atom typing for the CHARMM General Force Field
      (CGenFF). The CGenFF atom typer first associates attributes to the atoms and
      bonds in a molecule, such as valence, bond order, and ring membership among
      others. Of note are a number of features that are specifically required for
      CGenFF. This information is then used by the atom typing routine to assign CGenFF
      atom types based on a programmable decision tree. This allows for straightforward
      implementation of CGenFF's complicated atom typing rules and for equally
      straightforward updating of the atom typing scheme as the force field grows. The
      presented atom typer was validated by assigning correct atom types on 477 model
      compounds including in the training set as well as 126 test-set molecules that
      were constructed to specifically verify its different components. The program may
      be utilized via an online implementation at  https://www.paramchem.org/ .

PMID- 23146089
TI  - Epidemiology of general obesity, abdominal obesity and related risk factors in
      urban adults from 33 communities of Northeast China: the CHPSNE study.
AB  - BACKGROUND: Obesity increases the risk of many diseases. However, there has been
      little literature about the epidemiology of obesity classified by body mass index
      (BMI) or waist (abdominal obesity) among urban Chinese adults. This study is to
      fill the gap by assessing the prevalence of obesity and associated risk factors
      among urban Chinese adults. METHODS: A representative sample of 25,196 urban
      adults aged 18 to 74 years in Northeast China was selected and measurements of
      height, weight and waist circumference (WC) were taken from 2009-2010.
      Definitions of overweight and obesity by the World Health Organization (WHO) were
      used. RESULTS: The overall prevalence rates of general obesity and overweight
      classified by BMI were 15.0% (15.7% for men and 14.3% for women, p<0.01) and
      19.2% (20.8% for men and 17.7% for women, p<0.01), respectively, and the overall
      prevalence rate of abdominal obesity was 37.6% (31.1% for men and women 43.9% for
      women, p<0.01). Multivariable logistic regression showed that the elderly and
      those who had a history of parental obesity, alcohol drinking, or former
      cigarette smoking were at high risk of obesity classified by BMI or WC, whereas
      those with a higher level of education, higher family income, or a healthy and
      balanced diet were at low risk of obesity. Analysis stratified by gender showed
      that men with a higher level education level, a white-collar job, a cadre job, or
      higher family income were the high risk group, and women with a higher level of
      education or higher family income were the low risk group. CONCLUSIONS: Obesity
      and overweight have become epidemic in urban populations in China; associations
      of risk factors with obesity differ between men and women.

PMID- 23146090
TI  - Rheology of nanocrystalline cellulose aqueous suspensions.
AB  - The rheological properties and microstructure of nanocrystalline cellulose (NCC)
      aqueous suspensions have been investigated at different concentrations. The
      suspension is isotropic up to 3 wt %, and phase separates to liquid crystalline
      and isotropic domains at higher concentrations where the samples exhibit a
      fingerprint texture and the viscosity profile shows a three-region behavior,
      typical of liquid crystals. The suspension behaves as a rheological gel at even
      higher concentrations where the viscosity profile shows a single shear thinning
      behavior over the whole range of shear rates investigated. The effects of
      ultrasound energy and temperature on the rheological properties and structure of
      these suspensions were studied using polarized optical microscopy and rheometry.
      Our results indicate that the amount of applied ultrasound energy affects the
      microstructure of the suspensions and the pitch of the chiral nematic domains.
      The viscosity profile is changed significantly at low shear rates, whereas the
      viscosity of biphasic suspensions at intermediate and high shear rates decreased
      with increasing temperature. This suggests that, between 30 and 40  degrees C,
      structural rearrangement takes place. At higher concentrations of about 10 wt %,
      the temperature has no significant effect on viscosity; however, a marked
      increase in viscosity has been observed at around 50  degrees C. Finally, the Cox
      Merz rule was found to fail after a critical concentration, thereby implying
      significant structural formation. This critical concentration is much higher for
      sonicated compared to unsonicated suspensions.

PMID- 23146092
TI  - Albedo impact on the suitability of biochar systems to mitigate global warming.
AB  - Biochar application to agricultural soils can change the surface albedo which
      could counteract the climate mitigation benefit of biochar systems. However, the
      size of this impact has not yet been quantified. Based on empirical albedo
      measurements and literature data of arable soils mixed with biochar, a model for
      annual vegetation cover development based on satellite data and an assessment of
      the annual development of surface humidity, an average mean annual albedo
      reduction of 0.05 has been calculated for applying 30-32 Mg ha(-1) biochar on a
      test field near Bayreuth, Germany. The impact of biochar production and
      application on the carbon cycle and on the soil albedo was integrated into the
      greenhouse gas (GHG) balance of a modeled pyrolysis based biochar system via the
      computation of global warming potential (GWP) characterization factors. The
      analysis resulted in a reduction of the overall climate mitigation benefit of
      biochar systems by 13-22% due to the albedo change as compared to an analysis
      which disregards the albedo effect. Comparing the use of the same quantity of
      biomass in a biochar system to a bioenergy district heating system which replaces
      natural gas combustion, bioenergy heating systems achieve 99-119% of the climate
      benefit of biochar systems according to the model calculation.

PMID- 23146091
TI  - Biochemical and pharmacological characterization of AZD1981, an orally available
      selective DP2 antagonist in clinical development for asthma.
AB  - BACKGROUND AND PURPOSE: The discovery of DP2 as a second receptor for PGD2 has
      prompted the search for antagonists as potential novel therapies based on the
      associations between PGD2 and disease. Here we describe the biochemical and
      pharmacological properties of 4-(acetylamino)-3-[(4-chlorophenyl)thio]-2-methyl
      1H-indole-1-acetic acid (AZD1981), a novel DP2 receptor antagonist. EXPERIMENTAL
      APPROACH: Binding to DP2 , functional receptor pharmacology and selectivity were
      studied in both human and animal systems. KEY RESULTS: AZD1981 displaced radio
      labelled PGD2 from human recombinant DP2 with high potency (pIC50 = 8.4). Binding
      was reversible, non-competitive and highly selective against a panel of more than
      340 other enzymes and receptors, including DP1 (>1000-fold selective). AZD1981
      inhibited DP2 -mediated shape change and CD11b up-regulation in human
      eosinophils, shape change in basophils and chemotaxis of human eosinophils and
      Th2 cells with similar potency. AZD1981 exhibited good cross-species binding
      activity against mouse, rat, guinea pig, rabbit and dog DP2 . Evaluation in
      mouse, rat or rabbit cell systems was not possible as they did not respond to DP2
      agonists. Agonist responses were seen in guinea pig and dog, and AZD1981 blocked
      DP2 -mediated eosinophil shape change. Such responses were more robust in the
      guinea pig, where AZD1981 also blocked DP2 -dependent eosinophil emigration from
      bone marrow. CONCLUSIONS AND IMPLICATIONS: AZD1981 is a DP2 antagonist that
      blocks functional responses in eosinophils, Th2 cells and basophils. It exhibited
      similar potency irrespective of the cell type, DP2 agonist or species used. This
      selective orally active agent is currently under clinical evaluation as a
      potential therapeutic agent in respiratory diseases including asthma.

PMID- 23146093
TI  - Circulating natriuretic peptide concentrations in hyperthyroid cats.
AB  - OBJECTIVES: To assess the influence of thyroid function on natriuretic peptide
      concentration in hyperthyroid cats before and after treatment. METHODS: Serum
      natriuretic peptide concentration was measured in 61 hyperthyroid cats recruited
      from first-opinion clinics before and after treatment. RESULTS: Following
      successful treatment, total thyroxine, heart rate, systolic blood pressure and
      packed cell volume all decreased and bodyweight and creatinine concentrations
      increased. Furthermore, a significant (P < 0.001) decline in NT-proBNP
      concentration but not NT-proANP was identified. CLINICAL SIGNIFICANCE: Thyroid
      function has a modest but significant effect on NT-proBNP concentration. Thyroid
      status should be taken into account when interpreting NT-proBNP concentrations in
      cats.

PMID- 23146094
TI  - Harriscolex nathaliae N. Sp. (Cestoda: Proteocephalidea) from Pseudoplatystoma
      corruscans (Siluriformes: Pimelodidae) in the Parana River Basin, Argentina.
AB  - The proteocephalidean cestode Harriscolex nathaliae n. sp. (Proteocephalidae:
      Zygobothriinae) is described from the intestine of the spotted sorubim
      Pseudoplatystoma corruscans (Spix and Agassiz) (Siluriformes: Pimelodidae) from
      the Parana River basin in Argentina. This new species differs from the only
      species of the genus, Harriscolex kaparari (Woodland, 1935), which is a parasite
      of Pseudoplatystoma tigrinum (Linnaeus) from the Amazon River in Brazil, by its
      larger scolex (width of 450-750 MUm vs. 305-340 MUm), the position of the vagina
      in relation to the cirrus sac (anterior and posterior vs. only anterior), an
      asymmetrical vaginal sphincter, the arrangement of vitelline follicles (1 narrow
      longitudinal band on each side of the proglottid vs. 2 pairs of wide longitudinal
      bands on dorsal and ventral sides), and a higher number of uterine diverticula
      (22-45 vs. 16-20). Harriscolex nathaliae is covered with 2 types of microtriches,
      acicular filitriches and gladiate spinitriches.

PMID- 23146095
TI  - Combined paediatric NAFLD fibrosis index and transient elastography to predict
      clinically significant fibrosis in children with fatty liver disease.
AB  - BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) encompasses a spectrum of
      disease from simple steatosis to steatohepatitis, to fibrosis and cirrhosis. The
      paediatric NAFLD fibrosis index (PNFI) and transient elastography (TE) are
      potential noninvasive markers for fibrosis. To prospectively evaluate the
      performance of PNFI and TE in assessing clinically significant fibrosis in
      children with biopsy-proven NAFLD. METHODS: Our cohort consisted of 67
      consecutive children with biopsy-proven NAFLD. The stage of fibrosis was scored
      according to the Nonalcoholic Steatohepatitis Clinical Research Network. Fibrosis
      >= 2 was considered clinically significant. PNFI was calculated using age, waist
      circumference and triglycerides. TE was performed using the Fibroscan apparatus.
      RESULTS: Ten patients had fibrosis stage 2-3 and 57 patients had stage 0-1. Both
      PNFI and TE values were significantly higher in patients with significant
      fibrosis (P < 0.05). The area under the receiver operating characteristic (ROC)
      curve for predicting significant fibrosis of PNFI and TE were 0.747 and 1.00
      respectively (P = 0.005). The combined use of PNFI and TE could predict the
      presence or absence of clinically significant fibrosis in 98% of children with
      NAFLD. CONCLUSIONS: In children with NAFLD, the combination of PNFI and TE can be
      used to accurately assess the presence of clinically significant liver fibrosis.
      This will help to identify patients who should undergo liver biopsy because the
      confirmation of advanced fibrosis would lead to closer follow-up and screening
      for cirrhosis-related complications.

PMID- 23146096
TI  - A macrocyclic approach to tetracycline natural products. Investigation of
      transannular alkylations and Michael additions.
AB  - A new approach to the tetracycline core structure is presented. The pivotal
      intermediate is identified as macrocycle III. The two interior bonds (C4a-C12a
      and C5a-C11a) are to be constructed through sequential transannular Michael
      additions (III-II) and compression-promoted transannular isoxazole alkylations
      from intermediate II.

PMID- 23146097
TI  - Artificial redox-driven directionally controlled switches as a basis for redox
      driven molecular motors.
AB  - SIGNIFICANCE: This review relates to artificial redox-driven molecular devices.
      The advantages of using very simple chemical building blocks for the bottom-up
      design of nanoleveled functional motors and the importance of the
      unidirectionality of a switching process for the development of redox-driven
      molecular motors are discussed. Furthermore, the crucial difference between
      artificial molecular switches and motors is explained. RECENT ADVANCES: This
      review discusses few selected examples of redox-driven devices exhibiting
      partially complex-coupled movement sequences, which, however, due to the lack of
      an overall directionally controlled movement are not able to perform mechanical
      work on a molecular scale. Recent examples for redox-driven devices with at least
      one directionally controlled switching process as well as the proof for the
      unidirectionality of the switching process are presented. CRITICAL ISSUES: The
      challenge in designing directionally controlled switches is the fact that during
      the switching process, a configuration (or conformation) must be changed
      reversibly. This crucial process can be a flip caused by the change of the
      coordination sphere of a metal ion, a rotation around a C-C single bond, or
      around a C-C double bond. FUTURE DIRECTIONS: For future developments, we suggest
      designing artificial redox-based molecular motors in which the motion process of
      the presented directionally controlled switches are coupled with another
      switchable unit. The latter could also be switchable in a nondirected way.

PMID- 23146098
TI  - Quantitative analysis of human herpesvirus-6 genome in blood and bone marrow
      samples from Tunisian patients with acute leukemia: a follow-up study.
AB  - BACKGROUND: Infectious etiology in lymphoproliferative diseases has always been
      suspected. The pathogenic roles of human herpesvirus-6 (HHV-6) in acute leukemia
      have been of great interest. Discordant results to establish a link between HHV-6
      activation and the genesis of acute leukemia have been observed. The objective of
      this study was to evaluate a possible association between HHV-6 infection and
      acute leukemia in children and adults, with a longitudinal follow-up at
      diagnosis, aplasia, remission and relapse. METHODS: HHV-6 load was quantified by
      a quantitative real-time PCR in the blood and bone marrow samples from 37
      children and 36 adults with acute leukemia: 33 B acute lymphoblastic leukemia (B
      ALL), 6 T acute lymphoblastic leukemia (T-ALL), 34 acute myeloid leukemia (AML).
      RESULTS: HHV-6 was detected in 15%, 8%, 30% and 28% of the blood samples at
      diagnosis, aplasia, remission and relapse, respectively. The median viral loads
      were 138, 244, 112 and 78 copies/million cells at diagnosis, aplasia, remission
      and relapse, respectively. In the bone marrow samples, HHV-6 was detected in 5%,
      20% and 23% of the samples at diagnosis, remission and relapse, respectively. The
      median viral loads were 34, 109 and 32 copies/million cells at diagnosis,
      remission and relapse, respectively. According to the type of leukemia at
      diagnosis, HHV-6 was detected in 19% of the blood samples and in 7% of the bone
      marrow samples (with median viral loads at 206 and 79 copies/million cells,
      respectively) from patients with B-ALL. For patients with AML, HHV-6 was present
      in 8% of the blood samples and in 4% of the bone marrow samples (with median
      viral loads at 68 and 12 copies/million cells, respectively). HHV-6 was more
      prevalent in the blood samples from children than from adults (25% and 9%,
      respectively) and for the bone marrow (11% and 0%, respectively). All typable HHV
      6 were HHV-6B species. No link was shown between neither the clinical symptoms
      nor the abnormal karyotype and HHV-6 activation. A case of HHV-6 chromosomal
      integration was shown in one patient with AML. CONCLUSION: This study confirms
      the absence of role of HHV-6 in the genesis of acute leukemia but the virus was
      reactivated after chemotherapy treatment.

PMID- 23146099
TI  - Mutations arising during repair of chromosome breaks.
AB  - Mutations stimulate evolutionary change and lead to birth defects and cancer in
      humans as well as to antibiotic resistance in bacteria. According to the classic
      view, most mutations arise in dividing cells and result from uncorrected errors
      of S-phase DNA replication, which is highly accurate because of the involvement
      of selective DNA polymerases and efficient error-correcting mechanisms. In
      contrast, studies in bacteria and yeast reveal that DNA synthesis associated with
      repair of double-strand chromosomal breaks (DSBs) by homologous recombination is
      highly inaccurate, thus making DSBs and their repair an important source of
      mutations. Different error-prone mechanisms appear to operate in different repair
      scenarios. In the filling in of single-stranded DNA regions, error-prone
      translesion DNA polymerases appear to produce most errors. In contrast, in gene
      conversion gap repair and in break-induced replication, errors are independent of
      translesion polymerases, and many mutations have the signatures of template
      switching during DNA repair synthesis. DNA repair also appears to create complex
      copy-number variants. Overall, homologous recombination, which is traditionally
      considered a safe pathway of DSB repair, is an important source of mutagenesis
      that may contribute to human disease and evolution.

PMID- 23146100
TI  - Review article: liver transplantation for the pulmonary disorders of portal
      hypertension.
AB  - BACKGROUND: Liver transplantation is potentially a life-saving therapeutic
      intervention for patients with portopulmonary hypertension and hepatopulmonary
      syndrome. However, due to limited data, listing criteria for patients with these
      conditions have not been clearly established. Indeed, this has led some to
      speculate that transplantation may not be appropriate in cases of moderate-to
      severe portopulmonary hypertension and severe hepatopulmonary syndrome. AIM: To
      critically discuss the utility of LT for the treatment of hepatopulmonary
      syndrome and portopulmonary hypertension. METHODS: A literature search was
      conducted in 2012 on PubMed, Ovid Embase, Ovid Medline and Scopus using the
      following search terms: hepatopulmonary syndrome, portopulmonary hypertension,
      pulmonary arterial hypertension, liver transplantation. Relevant manuscripts were
      included in the review. RESULTS: Liver transplantation has established itself as
      an effective treatment for selected patients with hepatopulmonary syndrome and
      portopulmonary hypertension. A multidisciplinary team approach incorporating
      focused strategies (both pre- and post-operatively) aimed at improving
      oxygenation in patients with hepatopulmonary syndrome has led to a dramatic
      improvement in patient outcomes. Additionally, careful patient selection and the
      use of targeted pulmonary vascular therapies are successfully being used to treat
      portopulmonary hypertension and 'bridge' patients to successful liver
      transplantation. CONCLUSIONS: Liver transplantation is an effective therapy for
      patients with hepatopulmonary syndrome and portopulmonary hypertension. However,
      rigorous screening and early identification of these conditions allied with
      aggressive pre-operative optimisation of physiology and diligent post-operative
      care are imperative to ensuring a good outcome.

PMID- 23146101
TI  - Recognition of imipenem and meropenem by the RND-transporter MexB studied by
      computer simulations.
AB  - Basic understanding of the means by which multidrug efflux systems can
      efficiently recognize and transport drugs constitutes a fundamental step toward
      development of compounds able to tackle the continuous outbreak of new bacterial
      strains resistant to traditional antibiotics. We applied a series of
      computational techniques, from molecular docking to molecular dynamics
      simulations and free energy estimate methods, to determine the differences in the
      binding properties of imipenem and meropenem, two potent antibiotics of the
      carbapenem family, to MexB, the RND transporter of the major efflux system of
      Pseudomonas aeruginosa. We identified and characterized two affinity sites in the
      periplasmic domain of the transporter, sharing strong similarities with the
      distal and proximal binding pockets identified in AcrB, the homologue of MexB in
      Escherichia coli. According to our results, meropenem has a higher affinity to
      the distal binding pocket than imipenem while both compounds are weakly bound to
      the proximal pocket. This different behavior is mainly due to the hydration
      properties of the nonpharmacophore part of the two compounds, being that of
      imipenem less bulky and hydrophobic. Our data provide for the first time a
      rationale at molecular level for the experimental evidence indicating meropenem
      as a compound strongly affected by MexB contrary to imipenem, which is apparently
      poorly transported by the same pump.

PMID- 23146102
TI  - Rhizospheric NO affects N uptake and metabolism in Scots pine (Pinus sylvestris
      L.) seedlings depending on soil N availability and N source.
AB  - We investigated the interaction of rhizospheric nitric oxide (NO) concentration
      (i.e. low, ambient or high) and soil nitrogen (N) availability (i.e. low or high)
      with organic and inorganic N uptake by fine roots of Pinus sylvestris L.
      seedlings by (15) N feeding experiments under controlled conditions. N
      metabolites in fine roots were analysed to link N uptake to N nutrition. NO
      affected N uptake depending on N source and soil N availability. The suppression
      of nitrate uptake in the presence of ammonium and glutamine was overruled by high
      NO. The effects of NO on N uptake with increasing N availability showed different
      patterns: (1) increasing N uptake regardless of NO concentration (i.e. ammonium);
      (2) increasing N uptake only with high NO concentration (i.e. nitrate and
      arginine); and (3) decreasing N uptake (i.e. glutamine). At low N availability
      and high NO nitrate accumulated in the roots indicating insufficient substrates
      for nitrate reduction or its storage in root vacuoles. Individual amino acid
      concentrations were negatively affected with increasing NO (i.e. asparagine and
      glutamine with low N availability, serine and proline with high N availability).
      In conclusion, this study provides first evidence that NO affects N uptake and
      metabolism in a conifer.

PMID- 23146103
TI  - Care of children with diabetes as inpatients: frequency of admissions, clinical
      care and patient experience.
AB  - AIM: Hospital inpatient care for children with diabetes is frequently mentioned
      by parents as unsatisfactory. The aim of this study was to examine the reasons
      for inpatient admission of children with diabetes and to understand patient and
      carer experience in order to improve services. METHODS: Questionnaires were given
      to medical teams, parents and children during admissions of children with
      diabetes under 16 years of age in three regions of England. RESULTS: There were
      401 admissions over 6 months from 3247 patients: 334 (83%) emergency admissions
      and 59 (15%) elective; the reason is unknown in eight (2%). One hundred and forty
      three (36%) were emergency admissions with diabetic ketoacidosis/hyperglycaemia.
      Clinical teams reported adverse events around insulin administration in 25,
      hypoglycaemia (sometimes recurrent) in 120 and food provision in 14 admissions.
      Others included seven incidents around elective surgery. Diabetes clinical teams
      were not always informed about admissions and only 33% were informed within 2 h.
      Parents and children reported fewer problems: 62% were involved in care most of
      the time and 87% were able to give insulin. Most negative comments were about
      poor staff management of out-of-range blood glucose levels, knowledge of insulin
      pumps and care of children waiting in the emergency department. CONCLUSIONS:
      There were a large number of admissions and the majority were emergencies.
      Parents generally felt that they receive good care, although with some lack of
      knowledge amongst the ward staff. There were an unacceptable number of adverse
      incidents reported. We recommend that education of ward staff in diabetes is
      carried out regularly with reference to the standards of care.

PMID- 23146104
TI  - C(sp3)-C(sp3) and C(sp3)-H bond activation of 1,1-disubstituted cyclopentane.
AB  - The unprecedented C(sp(3))-C(sp(3)) bond cleavage of unactivated cyclopentane has
      been achieved. Rh(I)-catalyzed cycloaddition of allenylcyclopentane-alkynes
      produced in situ the 9-cyclopentyl-8-rhodabicyclo[4.3.0]nona-1,6-diene
      intermediates, which subsequently underwent [7+2] cycloaddition via beta-C
      elimination, affording bicyclo[7.4.0]tridecatriene derivatives in good yields.
      Changing the Rh(I) catalyst effected the Cgamma-H bond activation of the common 9
      cyclopentyl-8-rhodabicyclo[4.3.0]nona-1,6-diene intermediate to produce the novel
      spiro[2.4]heptane skeleton in a site-selective manner.

PMID- 23146105
TI  - Radial n-i-p structure SiNW-based microcrystalline silicon thin-film solar cells
      on flexible stainless steel.
AB  - Radial n-i-p structure silicon nanowire (SiNW)-based microcrystalline silicon
      thin-film solar cells on stainless steel foil was fabricated by plasma-enhanced
      chemical vapor deposition. The SiNW solar cell displays very low optical
      reflectance (approximately 15% on average) over a broad range of wavelengths (400
      to 1,100 nm). The initial SiNW-based microcrystalline (MUc-Si:H) thin-film solar
      cell has an open-circuit voltage of 0.37 V, short-circuit current density of
      13.36 mA/cm2, fill factor of 0.3, and conversion efficiency of 1.48%. After acid
      treatment, the performance of the modified SiNW-based MUc-Si:H thin-film solar
      cell has been improved remarkably with an open-circuit voltage of 0.48 V, short
      circuit current density of 13.42 mA/cm2, fill factor of 0.35, and conversion
      efficiency of 2.25%. The external quantum efficiency measurements show that the
      external quantum efficiency response of SiNW solar cells is improved greatly in
      the wavelength range of 630 to 900 nm compared to the corresponding planar film
      solar cells.

PMID- 23146106
TI  - Prognostic and predictive value of circulating tumor cell analysis in colorectal
      cancer patients.
AB  - OBJECTIVE: The aim of this study was to assess the prognostic and predictive
      values of circulating tumor cell (CTC) analysis in colorectal cancer patients.
      PATIENTS AND METHODS: Presence of CTCs was evaluated in 60 colorectal cancer
      patients before systemic therapy--from which 33 patients were also evaluable for
      CTC analysis during the first 3 months of treatment--through immunomagnetic
      enrichment, using the antibodies BM7 and VU1D9 (targeting mucin 1 and EpCAM,
      respectively), followed by real-time RT-PCR analysis of the tumor-associated
      genes KRT19, MUC1, EPCAM, CEACAM5 and BIRC5. RESULTS: Patients were stratified
      into groups according to CTC detection (CTC negative, when all marker genes were
      negative; and CTC positive when at least one of the marker genes was positive).
      Patients with CTC positivity at baseline had a significant shorter median
      progression-free survival (median PFS 181.0 days; 95% CI 146.9-215.1) compared
      with patients with no CTCs (median PFS 329.0 days; 95% CI 299.6-358.4; Log-rank P
      < .0001). Moreover, a statistically significant correlation was also founded
      between CTC detection during treatment and radiographic findings at the 6 month
      staging. This correlation applied to CTC results before therapy (odds ratio (OR),
      6.22), 1 to 4 weeks after beginning of treatment (OR, 5.50), 5 to 8 weeks after
      beginning of treatment (OR, 7.94) 9 to 12 weeks after beginning of treatment (OR,
      14.00) and overall CTC fluctuation during the course of treatment (OR, 20.57).
      CONCLUSION: The present study provides evidence of a strong correlation between
      CTC detection and radiographic disease progression in patients receiving
      chemotherapy for colorectal cancer. Our results suggest that in addition to the
      current prognostic factors, CTC analysis represent a potential complementary tool
      for prediction of colorectal cancer patients' outcome. Moreover, the present test
      allows for molecular characterization of CTCs, which may be of relevance to the
      creation of personalized therapies.

PMID- 23146108
TI  - Influence of meso-substituted tetraphenylporphyrin derivatives structure on their
      supramolecular organization in floating layers and Langmuir-Blodgett films.
AB  - To study the influence of structure peculiarities of porphyrin derivatives on
      their supramolecular organization in thin films, 15 new meso-substituted
      tetraphenylporphyrin derivatives and their metal complexes with substituents (
      OC(4)H(9) or -OC(16)H(33)) in para or ortho positions were studied. The films of
      the studied compounds were obtained by the Langmuir-Schaefer method. The behavior
      of porphyrin derivatives at the water-air interface was analyzed, and the
      conformity of the influence of molecular structure on supramolecular organization
      in floating layers and Langmuir-Blodgett films was defined. The absorption of
      these films over a wide spectral range was analyzed. The supramolecular
      organization of meso-substituted tetraphenylporphyrin derivatives was modeled and
      specified with the help of X-ray diffraction analysis. It was determined that the
      formation of monomolecular layers is typical for the compounds with short lateral
      substituents or without substituents. Tetraphenylporphyrins with extensive
      substituents can form a monolayer only when zinc is included in the molecular
      structure.

PMID- 23146107
TI  - Burden of paediatric influenza in Western Europe: a systematic review.
AB  - BACKGROUND: Influenza illness in children causes significant clinical and
      economic burden. Although some European countries have adopted influenza
      immunisation policies for healthy children, the debate about paediatric influenza
      vaccination in most countries of the European Union is ongoing. Our aim was to
      summarise influenza burden (in terms of health outcomes and economic burden) in
      children in Western Europe via a systematic literature review. METHODS: We
      conducted a systematic literature search of PubMed, EMBASE, and the Cochrane
      Library (1970-April 2011) and extracted data on influenza burden in children
      (defined as aged <= 18 years) from 50 publications (13 reporting laboratory
      confirmed influenza; 37 reporting influenza-like illness). RESULTS: Children with
      laboratory-confirmed influenza experienced hospitalisations (0.3%-20%), medical
      visits (1.7-2.8 visits per case), antibiotic prescriptions (7%-55%), and
      antipyretic or other medications for symptomatic relief (76%-99%); young children
      and those with severe illness had the highest rates of health care use. Influenza
      in children also led to absenteeism from day care, school, or work for the
      children, their siblings, and their parents. Average (mean or median) length of
      absence from school or day care associated with confirmed influenza ranged from
      2.8 to 12.0 days for the children, from 1.3 to 6.0 days for their siblings, and
      from 1.3 to 6.3 days for their parents. Influenza negatively affected health
      related quality of life in children with asthma, including symptoms and
      activities; this negative effect was smaller in vaccinated children than in non
      vaccinated children. CONCLUSIONS: Influenza burden in children is substantial and
      has a significant direct impact on the ill children and an indirect impact on
      their siblings and parents. The identified evidence regarding the burden of
      influenza may help inform both influenza antiviral use in children and paediatric
      immunisation policies in European countries.

PMID- 23146109
TI  - Oral health-related quality-of-life in homebound elderly dependent on moderate
      and substantial supportive care for daily living.
AB  - OBJECTIVES: To describe the oral health-related quality-of-life in homebound
      elderly dependent on moderate and substantial supportive care for daily living.
      MATERIALS AND METHODS: A total of 302 selected persons in three counties in
      Sweden over 65 years of age and in need of daily support from society
      participated in the study. Half of the participants had moderate needs of
      support, defined as supportive care of 15-50 h per month and half had substantial
      needs of supportive care, i.e. 3-times a day with a night overview. An oral
      examination was performed and structured questions were asked about general
      health and living conditions, medication, oral care routines and quality-of-life,
      using the instrument GOHAI (Geriatric Oral Health Assessment Instrument).
      RESULTS: Cardiovascular disease was common and an average of seven prescription
      drugs was used. More than half of the participants had dentures. The strongest
      correlation with GOHAI was the total number of teeth. There was a significant
      difference between individuals with moderate and substantial needs according to
      GOHAI, irrespective of gender. More elderly people with substantial needs of
      support had low GOHAI values. Decayed teeth, DT/T, root remnants and dry mouth
      were negatively correlated to GOHAI among individuals with substantial needs.
      CONCLUSIONS: This study found that elderly homebound individuals with substantial
      needs of supportive care had a lower quality-of-life than elderly homebound
      individuals with moderate needs of supportive care, although both medical and
      odontological variables were similar in the groups.

PMID- 23146111
TI  - Predicted redistribution of Ceratomyxa shasta genotypes with salmonid passage in
      the Deschutes River, Oregon.
AB  - A series of dams on the Deschutes River, Oregon, act as migration barriers that
      segregate the river system into upper and lower basins. Proposed fish passage
      between basins would reunite populations of native potamodromous fish and allow
      anadromous fish of Deschutes River origin access to the upper basin. We assessed
      the potential redistribution of host-species-specific genotypes (O, I, II, III)
      of the myxozoan parasite Ceratomyxa shasta that could occur with fish passage and
      examined the influence of nonnative fish on genotype composition. To determine
      the present distribution of the parasite genotypes, we exposed eight salmonid
      species-three native and five stocked for sport fishing-in present and predicted
      anadromous salmonid habitats. We monitored fish for infection by C. shasta and
      sequenced a section of the parasite ribosomal DNA gene from fish and water
      samples to determine parasite genotype. Genotype O was present in both upper and
      lower basins and detected only in steelhead Oncorhynchus mykiss. Genotype I was
      spatially limited to the lower basin, isolated predominantly from Chinook salmon
      O. tshawytscha, and lethal for this species only. Genotype II was detected in
      both basins and in multiple species, but only as a minor component of the
      infection. Genotype III was also present in both basins, had a wide host range,
      and caused mortality in native steelhead and multiple nonnative species. Atlantic
      salmon Salmo salar and kokanee O. nerka were the least susceptible to infection
      by any genotype of C. shasta. Our findings confirmed the host-specific patterns
      of C. shasta infections and indicated that passage of Chinook salmon would
      probably spread genotype I into the upper Deschutes River basin, but with little
      risk to native salmonid populations.

PMID- 23146112
TI  - Numerical errors in minimization based binding energy calculations.
AB  - This work examines the effect of small input perturbations on binding energies
      computed from differences between energy minimized structures, such as the Prime
      MM-GBSA and MOE MM-GB/VI methods. The applied perturbations include translations
      of the cognate ligand in the binding site by a maximum of 0.1 A along each
      coordinate or the permutation of the order of atoms of the cognate ligand without
      any changes to the atom coordinates. These seemingly inconsequential input
      changes can lead to as much as 17 kcal/mol differences in the computed binding
      energy. The calculated binding energies cluster around discrete values, which
      correspond to specific ligand poses. It appears that the largest variations are
      observed for target-ligand systems in which there is a possibility for multiple
      poses with strong hydrogen bonds. The barriers between different poses can appear
      fractal-like, making it difficult to predict which solution will be produced from
      a given input. Including protein flexibility in MM-GBSA calculations further
      increases numerical instability, and the protein strain terms seem to be the
      major factor contributing to this sensitivity. In such calculations it appears
      unwise to extend the flexible region beyond 6 A.

PMID- 23146110
TI  - Andrographolide protects against cigarette smoke-induced oxidative lung injury
      via augmentation of Nrf2 activity.
AB  - BACKGROUND AND PURPOSE: Cigarette smoke is a major cause for chronic obstructive
      pulmonary disease (COPD). Andrographolide is an active biomolecule isolated from
      the plant Andrographis paniculata. Andrographolide has been shown to activate
      nuclear factor erythroid-2-related factor 2 (Nrf2), a redox-sensitive antioxidant
      transcription factor. As Nrf2 activity is reduced in COPD, we hypothesize that
      andrographolide may have therapeutic value for COPD. EXPERIMENTAL APPROACH:
      Andrographolide was given i.p. to BALB/c mice daily 2h before 4% cigarette smoke
      exposure for 1h over five consecutive days. Bronchoalveolar lavage fluid and
      lungs were collected for analyses of cytokines, oxidative damage markers and
      antioxidant activities. BEAS-2B bronchial epithelial cells were exposed to
      cigarette smoke extract (CSE) and used to study the antioxidant mechanism of
      action of andrographolide. KEY RESULTS: Andrographolide suppressed cigarette
      smoke-induced increases in lavage fluid cell counts; levels of IL-1beta, MCP-1,
      IP-10 and KC; and levels of oxidative biomarkers 8-isoprostane, 8-OHdG and 3
      nitrotyrosine in a dose-dependent manner. Andrographolide promoted inductions of
      glutathione peroxidase (GPx) and glutathione reductase (GR) activities in lungs
      from cigarette smoke-exposed mice. In BEAS-2B cells, andrographolide markedly
      increased nuclear Nrf2 accumulation, promoted binding to antioxidant response
      element (ARE) and total cellular glutathione level in response to CSE.
      Andrographolide up-regulated ARE-regulated gene targets including glutamate
      cysteine ligase catalytic (GCLC) subunit, GCL modifier (GCLM) subunit, GPx, GR
      and heme oxygenase-1 in BEAS-2B cells in response to CSE. CONCLUSIONS:
      Andrographolide possesses antioxidative properties against cigarette smoke
      induced lung injury probably via augmentation of Nrf2 activity and may have
      therapeutic potential for treating COPD.

PMID- 23146113
TI  - Intracranial migration of Eucoleus (Capillaria) boehmi in a dog.
AB  - A 4-year-old, spayed-female great Dane was referred for surgical treatment of a
      suspected meningioma, diagnosed on magnetic resonance imaging 10 days prior to
      presentation. The suspected meningioma was removed via image-guided stereotactic
      craniotomy. Histopathological diagnosis was severe, locally extensive, chronic
      meningoencephalitis with an intralesional nematode egg. The egg was
      morphologically consistent with Eucoleus boehmi, and aberrant migration into the
      cranial cavity was the presumed cause of this lesion. Three faecal samples were
      collected and revealed 4+ E. boehmi eggs. Treatment involved 110 mg/kg
      fenbendazole (Panacur, Intervet) orally twice daily for 14 days. Nematodes
      including E. boehmi are a previously un-recognised source of intracranial disease
      in dogs, and should be considered as a differential for mass-like lesions
      visualised by magnetic resonance imaging.

PMID- 23146114
TI  - The effect of patients' preference on outcome in the EVerT cryotherapy versus
      salicylic acid for the treatment of plantar warts (verruca) trial.
AB  - BACKGROUND: Randomised controlled trials are widely accepted as the gold
      standard method to evaluate medical interventions, but they are still open to
      bias. One such bias is the effect of patient's preference on outcome measures.
      The aims of this study were to examine whether patients' treatment preference
      affected clearance of plantar warts and explore whether there were any
      associations between patients' treatment preference and baseline variables in the
      EverT trial. METHODS: Two hundred and forty patients were recruited from
      University podiatry schools, NHS podiatry clinics and primary care. Patients were
      aged 12 years and over and had at least one plantar wart which was suitable for
      treatment with salicylic acid and cryotherapy. Patients were asked their
      treatment preference prior to randomisation. The Kruskal-Wallis test was
      performed to test the association between preference group and continuous
      baseline variables. The Fisher's exact test was performed to test the association
      between preference group and categorical baseline variables. A logistic
      regression analysis was undertaken with verruca clearance (yes or no) as the
      dependent variable and treatment, age, type of verruca, previous treatment,
      treatment preference as independent variables. Two analyses were undertaken, one
      using the health professional reported outcome and one using the patient's self
      reported outcomes. Data on whether the patient found it necessary to stop the
      treatment to which they had been allocated and whether they started another
      treatment were summarised by treatment group. RESULTS: Pre-randomisation
      preferences were: 10% for salicylic acid; 42% for cryotherapy and 48% no
      treatment preference. There was no evidence of an association between treatment
      preference group and either patient (p=0.95) or healthcare professional (p=0.46)
      reported verruca clearance rates. There was no evidence of an association between
      preference group and any of the baseline variables except gender, with more
      females expressing a preference for salicylic acid (p=0.004). There was no
      evidence that the number of times salicylic acid was applied was different
      between the preference groups at one week (p=0.89) or at three weeks (p=0.24).
      Similarly, for the number of clinic visits for cryotherapy (p=0.71) CONCLUSIONS:
      This secondary analysis showed no evidence to suggest that patients' baseline
      preferences affected verruca clearance rates or adherence with the treatment.
      TRIAL REGISTRATION: Current Controlled Trials ISRCTN18994246 and National
      Research Register N0484189151.

PMID- 23146115
TI  - Differentiation of the microfilariae of Dirofilaria immitis and Dirofilaria
      repens in stained blood films.
AB  - An examination was made of Giemsa-stained microfilariae in thin blood films from
      (n = 9) dogs naturally or experimentally infected with Dirofilaria immitis or
      Dirofilaria repens. Morphological measurements (total length, length of cephalic
      space, anterior end to nerve ring and last body nucleus, and nucleus-free tail
      tip) were made on 2-6 microfilariae from each dog with the use of digitally
      captured images and imaging software. The microfilariae of D. repens were
      significantly greater (P < 0.001) in all measured dimensions except for the
      length of the cephalic space, which was significantly shorter (P < 0.001) than
      that of D. immitis. The cephalic space of D. repens was characterized by being
      short and routinely being terminated by a distinct pair of nuclei that were
      separate from the remaining somatic nuclei of the microfilaria. The cephalic
      space of the smaller microfilaria of D. immitis was longer and did not have the
      distinct nuclei separated from the somatic column nuclei near the anterior end.
      The character of the cephalic space seems to be a criterion that could be
      routinely used for the easy differentiation of these 2 microfilariae in stained
      blood films.

PMID- 23146116
TI  - A proof for loop-law constraints in stoichiometric metabolic networks.
AB  - BACKGROUND: Constraint-based modeling is increasingly employed for metabolic
      network analysis. Its underlying assumption is that natural metabolic phenotypes
      can be predicted by adding physicochemical constraints to remove unrealistic
      metabolic flux solutions. The loopless-COBRA approach provides an additional
      constraint that eliminates thermodynamically infeasible internal cycles (or
      loops) from the space of solutions. This allows the prediction of flux solutions
      that are more consistent with experimental data. However, it is not clear if this
      approach over-constrains the models by removing non-loop solutions as well.
      RESULTS: Here we apply Gordan's theorem from linear algebra to prove for the
      first time that the constraints added in loopless-COBRA do not over-constrain the
      problem beyond the elimination of the loops themselves. CONCLUSIONS: The loopless
      COBRA constraints can be reliably applied. Furthermore, this proof may be adapted
      to evaluate the theoretical soundness for other methods in constraint-based
      modeling.

PMID- 23146118
TI  - Abstracts of the Australian Association of Gerontology, 45th National Conference.
      November 20-23, 2012. Brisbane, Australia.

PMID- 23146117
TI  - Liver transplantation for overlap syndromes of autoimmune liver diseases.
AB  - BACKGROUND/AIMS: The term overlap syndrome describes variant forms of autoimmune
      hepatitis (AIH) that present in combination with either characteristics of
      primary biliary cirrhosis (PBC), or primary sclerosing cholangitis (PSC). This
      study analysed the outcomes and evidence of recurrent liver disease after liver
      transplantation in patients with overlap syndromes compared with patients
      transplanted for single autoimmune liver disease. METHODS: We evaluated 231 adult
      patients who received a liver transplant as a result of autoimmune liver
      diseases; including 103 with PBC, 84 with PSC, 32 with AIH and 12 with overlap
      syndrome (7 AIH-PBC and 5 AIH-PSC). RESULTS: Patients with overlap syndromes had
      a higher probability of recurrence than patients with a single autoimmune liver
      disease (5 years: 53% vs. 17%; 10 years 69% vs. 29%, P = 0.001). Furthermore,
      median time for recurrence in overlap syndrome was shorter when compared with
      patients with single autoimmune liver disease (67 +/- 20 vs. 172 +/- 9 months, P
      = 0.001). The diagnosis of overlap syndrome was independently associated with a
      higher risk to develop recurrent disease than patients transplanted with a single
      disease (HR 3.39, P = 0.007). Median graft survival for overlap syndrome was 123
      +/- 16 months and 180 +/- 8 months in patients with single autoimmune liver
      diseases (P = 0.9), and median patient survival for overlap syndrome was 135 +/-
      13 months and 193 +/- 8 months in patients with single autoimmune liver disease
      (P = 0.6). CONCLUSIONS: Patients that received an allograft for end-stage liver
      disease secondary to overlap syndrome had a higher rate of disease recurrence
      when compared with transplant recipients with single autoimmune liver disorders,
      but the overall survival was comparable.

PMID- 23146119
TI  - Redox molecular machines involved in tumor progression.
AB  - SIGNIFICANCE: We herein review recent advances on the role exerted by protein
      redox machines engaged in tumor progression, focusing on cell adhesion and
      migration, regulation of transcriptional response, and tumor metabolic
      reprogramming, all features belonging to the new hallmarks of cancer. RECENT
      ADVANCES: Several recent insights have reported that oxidative stress, either due
      to intracellular sources of oxidants, which are frequently deregulated in cancers
      or to microenvironment factors as hypoxia or stromal cell contact, plays a key
      role in tumor malignancy, as well as in metabolic pathways control. Indeed, many
      proteins behave as sensors of intracellular oxidative stress, including protein
      tyrosine kinases and phosphatases, transcription factors as p53, forkhead box
      class-Os, nuclear respiratory factor-2, nuclear factor-kB, hypoxia inducible
      factor, enzymes involved in glycolysis or penthose phosphate pathway as pyruvate
      kinase-M2 and adenylate monophosphate kinase, or DNA repair enzymes as Ataxia
      Teleangectasia Mutated. All these proteins have been reported to play essential
      roles during cancer progression and their sensitivity to oxidative stress has
      added new levels of complexity to the cancer field. CRITICAL ISSUES: Main
      significant issues that need to be addressed in redox cancer biology are (i)
      sensitivity to a different level of oxidative stress of sensors, that is, they
      can respond to different oxidative insults/signals, and (ii) the real
      susceptibility of cancer cells to redox-based therapies due to the acknowledged
      plasticity of cancer cells to develop adoptive strategies. FUTURE DIRECTIONS:
      Definitely, redox machines have the potentiality to develop into novel biomarkers
      and related target therapies should attain the goal of personalized medicine in
      the fight against cancer.

PMID- 23146120
TI  - Body fat predicts an increase and limb muscle strength predicts a decrease in
      leptin in older adults over 2.6 years.
AB  - OBJECTIVE: Obesity is characterized by hyperleptinaemia, which is associated with
      diabetes, hypertension and coronary heart disease. The aim of this study was to
      determine if body fat and muscle measures predict the natural increase in leptin
      over 2.6 years in older adults. METHODS: A total of 190 subjects (50% females)
      aged between 50 and 79 years were selected to perform the serum measurements for
      leptin. Height and weight were measured and body mass index (BMI) was calculated.
      Fat and lean mass of the whole body and the trunk were acquired through dual
      energy X-ray absorptiometry (DXA). Leg muscle strength and handgrip strength were
      measured using dynamometry. RESULTS: In multivariable analyses, leg muscle
      strength was negatively associated with both baseline leptin (beta: -0.05 MUg/l
      per kg, 95% CI: -0.08, -0.02) and follow-up leptin (beta: -0.04 MUg/l per kg, 95%
      CI: -0.07, -0.01). BMI, and percentage total fat and trunk fat and their
      respective change per annum (cpa) were significantly and positively associated
      with leptin. Lean mass was negatively associated with baseline leptin. Gender
      specific analyses produced similar associations between leg muscle strength, fat
      measures and follow-up leptin in males and females. CONCLUSION: Besides positive
      associations between body fat, trunk fat and leptin, we found that leg muscle
      strength was negatively associated with leptin after 2.6 years in a sample of
      older population. This suggests that interventions to maintain or increase muscle
      strength may have a protective effect on hyperleptinaemia.

PMID- 23146121
TI  - Aqueous pathways dominate permeation of solutes across Pisum sativum seed coats
      and mediate solute transport via diffusion and bulk flow of water.
AB  - The permeability of seed coats to solutes either of biological or anthropogenic
      origin plays a major role in germination, seedling growth and seed treatment by
      pesticides. An experimental set-up was designed for investigating the mechanisms
      of seed coat permeation, which allows steady-state experiments with isolated seed
      coats of Pisum sativum. Permeances were measured for a set of organic model
      compounds with different physicochemical properties and sizes. The results show
      that narrow aqueous pathways dominate the diffusion of solutes across pea seed
      coats, as indicated by a correlation of permeances with the molecular sizes of
      the compounds instead of their lipophilicity. Further indicators for an aqueous
      pathway are small size selectivity and a small effect of temperature on
      permeation. The application of an osmotic water potential gradient across
      isolated seed coats leads to an increase in solute transfer, indicating that the
      aqueous pathways form a water-filled continuum across the seed coat allowing the
      bulk flow of water. Thus, the uptake of organic solutes across pea testae has two
      components: (1) by diffusion and (2) by bulk water inflow, which, however, is
      relevant only during imbibition.

PMID- 23146122
TI  - Mild Rh(III)-catalyzed C-H activation and annulation with alkyne MIDA boronates:
      short, efficient synthesis of heterocyclic boronic acid derivatives.
AB  - Taking advantage of Rh(III)-catalyzed C-H activation reactions, we have developed
      a mild, short, and efficient method for the synthesis of bench-stable 3
      isoquinolone MIDA boronates. The reaction is practical and scalable. The product
      formed has been applied in the Suzuki-Miyaura reaction with high efficiency. This
      strategy has also been successfully expanded to the synthesis of MIDA boronate
      functionalized heterocycles such as isoquinoline, pyrrole, and indole.

PMID- 23146123
TI  - The politics of probiotics: probiotics, necrotizing enterocolitis and the ethics
      of neonatal research.

PMID- 23146124
TI  - Regulation of leukotriene and 5oxoETE synthesis and the effect of 5-lipoxygenase
      inhibitors:  a mathematical modeling approach.
AB  - BACKGROUND: 5-lipoxygenase (5-LO) is a key enzyme in the synthesis of
      leukotrienes and 5-Oxo-6E,8Z,11Z,14Z-eicosatetraenoic acid (oxoETE). These
      inflammatory signaling molecules play a role in the pathology of asthma and so 5
      LO inhibition is a promising target for asthma therapy. The 5-LO redox inhibitor
      zileuton (Zyflo IR/CR((r))) is currently marketed for the treatment of asthma in
      adults and children, but widespread use of zileuton is limited by its
      efficacy/safety profile, potentially related to its redox characteristics. Thus,
      a quantitative, mechanistic description of its functioning may be useful for
      development of improved anti-inflammatory targeting this mechanism. RESULTS: A
      mathematical model describing the operation of 5-LO, phospholipase A2,
      glutathione peroxidase and 5-hydroxyeicosanoid dehydrogenase was developed. The
      catalytic cycles of the enzymes were reconstructed and kinetic parameters
      estimated on the basis of available experimental data. The final model describes
      each stage of cys-leukotriene biosynthesis and the reactions involved in oxoETE
      production. Regulation of these processes by substrates (phospholipid
      concentration) and intracellular redox state (concentrations of reduced
      glutathione, glutathione (GSH), and lipid peroxide) were taken into account. The
      model enabled us to reveal differences between redox and non-redox 5-LO
      inhibitors under conditions of oxidative stress. Despite both redox and non-redox
      inhibitors suppressing leukotriene A4 (LTA4) synthesis, redox inhibitors are
      predicted to increase oxoETE production, thus compromising efficacy. This
      phenomena can be explained in terms of the pseudo-peroxidase activity of 5-LO and
      the ability of lipid peroxides to transform 5-LO into its active form even in the
      presence of redox inhibitors. CONCLUSIONS: The mathematical model developed
      described quantitatively different mechanisms of 5-LO inhibition and simulations
      revealed differences between the potential therapeutic outcomes for these
      mechanisms.

PMID- 23146126
TI  - A study of photomodulated reflectance on staircase-like, n-doped GaAs/AlxGa1-xAs
      quantum well structures.
AB  - In this study, photomodulated reflectance (PR) technique was employed on two
      different quantum well infrared photodetector (QWIP) structures, which consist of
      n-doped GaAs quantum wells (QWs) between undoped AlxGa1-xAs barriers with three
      different x compositions. Therefore, the barrier profile is in the form of a
      staircase-like barrier. The main difference between the two structures is the
      doping profile and the doping concentration of the QWs. PR spectra were taken at
      room temperature using a He-Ne laser as a modulation source and a broadband
      tungsten halogen lamp as a probe light. The PR spectra were analyzed using
      Aspnes' third derivative functional form.Since the barriers are staircase-like,
      the structure has different ground state energies; therefore, several optical
      transitions take place in the spectrum which cannot be resolved in a conventional
      photoluminescence technique at room temperature. To analyze the experimental
      results, all energy levels in the conduction and in the valance band were
      calculated using transfer matrix technique, taking into account the effective
      mass and the parabolic band approximations. A comparison of the PR results with
      the calculated optical transition energies showed an excellent agreement. Several
      optical transition energies of the QWIP structures were resolved from PR
      measurements. It is concluded that PR spectroscopy is a very useful experimental
      tool to characterize complicated structures with a high accuracy at room
      temperature.

PMID- 23146125
TI  - Targeted delivery of doxorubicin through conjugation with EGF receptor-binding
      peptide overcomes drug resistance in human colon cancer cells.
AB  - BACKGROUND AND PURPOSE: Induction of multidrug resistance by doxorubicin (DOX),
      together with non-specific toxicities, has restricted DOX-based chemotherapy.
      Recently, we demonstrated that DOX conjugated with an EGF receptor-binding
      peptide (DOX-EBP) had enhanced anticancer efficacy and reduced systemic toxicity
      when targeting EGF receptor-overexpressing tumours. Here we investigated whether
      DOX-EBP is able to overcome drug resistance and the underlying molecular
      mechanisms. EXPERIMENTAL APPROACH: DOX-resistant SW480/DOX cells were derived
      from non-resistant SW480 cells by stepwise exposure to increasing concentrations
      of DOX, and P-glycoprotein overexpression induced by DOX was confirmed by Western
      blotting. Cytotoxicity and intracellular distribution of drugs were evaluated by
      MTT assay and fluorescence microscopy respectively. EGF receptor-mediated
      endocytosis was determined in EGF receptor and endocytosis inhibition assays.
      Drug accumulation in tumour cells and murine xenografts was determined by HPLC.
      KEY RESULTS: The cytotoxicity and accumulation of DOX-EBP in SW480/DOX cells were
      almost the same as in SW480 cells, but those of free DOX were reduced. DOX-EBP
      accumulation was prevented by inhibitors of both EGF receptors and endocytosis,
      suggesting EGF receptors mediate endocytotic uptake. Tumour accumulation of DOX
      EBP was significantly higher than free DOX in mice, and the levels of DOX-EBP
      were similar in DOX-resistant and non-resistant tumour tissues. Importantly, DOX
      EBP, but not free DOX, was effective at inhibiting solid tumour growth and
      increased survival rate in both sensitive and resistant models. CONCLUSION AND
      IMPLICATIONS: DOX-EBP can overcome DOX resistance of tumour cells and increase in
      vivo antitumour efficacy. Therefore, it has the potential to be a potent
      therapeutic agent for treating drug-resistant cancers.

PMID- 23146128
TI  - Identification of stable normalization genes for quantitative real-time PCR in
      porcine articular cartilage.
AB  - BACKGROUND: Expression levels for genes of interest must be normalized with an
      appropriate reference, or housekeeping gene, to make accurate comparisons of
      quantitative real-time PCR results. The purpose of this study was to identify the
      most stable housekeeping genes in porcine articular cartilage subjected to a
      mechanical injury from a panel of 10 candidate genes. RESULTS: Ten candidate
      housekeeping genes were evaluated in three different treatment groups of
      mechanically impacted porcine articular cartilage. The genes evaluated were: beta
      actin, beta-2-microglobulin, glyceraldehyde-3-phosphate dehydrogenase,
      hydroxymethylbilane synthase, hypoxanthine phosphoribosyl transferase,
      peptidylprolyl isomerase A (cyclophilin A), ribosomal protein L4, succinate
      dehydrogenase flavoprotein subunit A, TATA box binding protein, and tyrosine 3
      monooxygenase/tryptophan 5-monooxygenase activation protein-zeta polypeptide. The
      stability of the genes was measured using geNorm, BestKeeper, and NormFinder
      software. The four most stable genes measured via geNorm were (most to least
      stable) succinate dehydrogenase flavoprotein, subunit A, peptidylprolyl isomerase
      A, glyceraldehyde-3-phosphate dehydrogenase, beta actin; the four most stable
      genes measured via BestKeeper were glyceraldehyde-3-phosphate dehydrogenase,
      peptidylprolyl isomerase A, beta actin, succinate dehydrogenase flavoprotein,
      subunit A; and the four most stable genes measured via NormFinder were
      peptidylprolyl isomerase A, succinate dehydrogenase flavoprotein, subunit A,
      glyceraldehyde-3-phosphate dehydrogenase, beta actin. CONCLUSIONS: BestKeeper,
      geNorm, and NormFinder all generated similar results for the most stable genes in
      porcine articular cartilage. The use of these appropriate reference genes will
      facilitate accurate gene expression studies of porcine articular cartilage and
      suggest appropriate housekeeping genes for articular cartilage studies in other
      species.

PMID- 23146127
TI  - Statistical distributions of test statistics used for quantitative trait
      association mapping in structured populations.
AB  - BACKGROUND: Spurious associations between single nucleotide polymorphisms and
      phenotypes are a major issue in genome-wide association studies and have led to
      underestimation of type 1 error rate and overestimation of the number of
      quantitative trait loci found. Many authors have investigated the influence of
      population structure on the robustness of methods by simulation. This paper is
      aimed at developing further the algebraic formalization of power and type 1 error
      rate for some of the classical statistical methods used: simple regression, two
      approximate methods of mixed models involving the effect of a single nucleotide
      polymorphism (SNP) and a random polygenic effect (GRAMMAR and FASTA) and the
      transmission/disequilibrium test for quantitative traits and nuclear families.
      Analytical formulae were derived using matrix algebra for the first and second
      moments of the statistical tests, assuming a true mixed model with a polygenic
      effect and SNP effects. RESULTS: The expectation and variance of the test
      statistics and their marginal expectations and variances according to the
      distribution of genotypes and estimators of variance components are given as a
      function of the relationship matrix and of the heritability of the polygenic
      effect. These formulae were used to compute type 1 error rate and power for any
      kind of relationship matrix between phenotyped and genotyped individuals for any
      level of heritability. For the regression method, type 1 error rate increased
      with the variability of relationships and with heritability, but decreased with
      the GRAMMAR method and was not affected with the FASTA and quantitative
      transmission/disequilibrium test methods. CONCLUSIONS: The formulae can be easily
      used to provide the correct threshold of type 1 error rate and to calculate the
      power when designing experiments or data collection protocols. The results
      concerning the efficacy of each method agree with simulation results in the
      literature but were generalized in this work. The power of the GRAMMAR method was
      equal to the power of the FASTA method at the same type 1 error rate. The power
      of the quantitative transmission/disequilibrium test was low. In conclusion, the
      FASTA method, which is very close to the full mixed model, is recommended in
      association mapping studies.

PMID- 23146129
TI  - Three-dimensional electron energy deposition modeling of cathodoluminescence
      emission near threading dislocations in GaN and electron-beam lithography
      exposure parameters for a PMMA resist.
AB  - The Monte Carlo software CASINO has been expanded with new modules for the
      simulation of complex beam scanning patterns, for the simulation of
      cathodoluminescence (CL), and for the calculation of electron energy deposition
      in subregions of a three-dimensional (3D) volume. Two examples are presented of
      the application of these new capabilities of CASINO. First, the CL emission near
      threading dislocations in gallium nitride (GaN) was modeled. The CL emission
      simulation of threading dislocations in GaN demonstrated that a better signal-to
      noise ratio was obtained with lower incident electron energy than with higher
      energy. Second, the capability to simulate the distribution of the deposited
      energy in 3D was used to determine exposure parameters for polymethylmethacrylate
      resist using electron-beam lithography (EBL). The energy deposition dose in the
      resist was compared for two different multibeam EBL schemes by changing the
      incident electron energy.

PMID- 23146130
TI  - Determination of VITA Classical shades with the 3D-Master shade guide.
AB  - OBJECTIVES: Because of its good matching performance the VITA 3D-Master shade
      guide (3D) is frequently used for determination of tooth color. Numerous
      composites/ceramics are, however, available in VITA Classical (VC) shades only.
      The objective of this study was to investigate the possibility of performing a
      shade match with 3D Master and converting this result via a table in a VC shade
      (indirect method) without this resulting in an apparent inferior shade matching
      in comparison with direct shade matching with the VC. METHODS: Experiments were
      performed with an artificial, computer-generated tooth color space. Conversion
      tables were generated by calculating the color difference (DeltaE) between a 3D
      shade and the closest VC shade (simple conversion table) and with the aid of
      optimization procedures. Statistical differences between the direct and indirect
      methods and between the indirect methods were assessed by use of a U-test.
      RESULTS: Median DeltaE was 2.38 for direct matching with the VC and 2.86 for
      indirect matching by use of a simple conversion table (p < 0.01). Optimized
      tables performed slightly better (median DeltaE = 2.81). CONCLUSIONS: Within the
      limitations of the study, it is usually possible to determine tooth color with
      the 3D and convert it, via a table, into a VC shade without adding a clinically
      apparent error to the direct shade match with the VC.

PMID- 23146131
TI  - Long-term outcome in dogs undergoing mitral valve repair with suture annuloplasty
      and chordae tendinae replacement.
AB  - Mitral valve repair under cardiopulmonary bypass was performed in three dogs with
      clinical signs associated with mitral regurgitation that were not controlled by
      medication. Mitral valve repair comprised circumferential annuloplasty and
      chordal replacement with expanded polytetrafluoroethylene. One dog died 2 years
      after surgery because of severe mitral regurgitation resulting from partial
      circumferential suture detachment. The others survived for over 5 years, but mild
      mitral valve stenosis persisted in one. The replaced chordae did not rupture in
      any dog. Mitral valve repair appears to be an effective treatment for mitral
      regurgitation in dogs. Chordal replacement with expanded polytetrafluoroethylene
      is a feasible technique, demonstrating long-term durability in dogs. However,
      mitral annuloplasty techniques need improvement.

PMID- 23146132
TI  - Ethnic differences in intraocular pressure reduction and changes in anterior
      segment biometric parameters following cataract surgery by phacoemulsification.
AB  - BACKGROUND: To determine the association between ethnicity and changes in
      intraocular pressure and anterior segment biometric parameters following cataract
      surgery by phacoemulsification in nonglaucomatous subjects. DESIGN: Prospective
      clinical cohort study. PARTICIPANTS: Caucasian and Asian subjects. METHODS:
      Customized software was used to calculate parameters from anterior segment
      optical coherence tomography images obtained preoperatively and at 3 months
      following cataract surgery by phacoemulsification. The percentage changes in
      intraocular pressure and anterior segment biometric parameters following cataract
      surgery by phacoemulsification were modelled as a function of ethnicity using
      linear mixed-effects regression, a likelihood ratio test function that adjusted
      for age, sex and the use of both eyes in the same subject, to determine the
      association between ethnicity and postoperative outcomes. MAIN OUTCOME MEASURES:
      Intraocular pressure, angle opening distance, anterior chamber depth, anterior
      chamber volume, and angle recess area. RESULTS: Fifty Asian and 23 Caucasian
      nonglaucomatous eyes were analysed. Postoperative decrease in intraocular
      pressure and increases in angle opening distance, anterior chamber depth,
      anterior chamber volume and angle recess area were observed within each ethnic
      group (P < 0.005). The percent changes in intraocular pressure, angle opening
      distance, anterior chamber depth, anterior chamber volume and angle recess area
      did not differ between ethnic groups (P > 0.05). CONCLUSIONS: In this study,
      regardless of ethnic classification, subjects who received cataract surgery by
      phacoemulsification experienced a significant postoperative decrease in
      intraocular pressure and increases in angle opening distance, anterior chamber
      depth, anterior chamber volume and angle recess area. The percent changes in
      postoperative outcomes did not differ significantly by ethnicity.

PMID- 23146133
TI  - Association between white matter hyperintensity severity and cognitive impairment
      according to the presence of the apolipoprotein E (APOE) epsilon4 allele in the
      elderly: retrospective analysis of data from the CREDOS study.
AB  - OBJECTIVE: To investigate the effect of white matter hyperintensity (WMH)
      severity on cognitive function according to presence of the apolipoprotein E
      (APOE) epsilon4 allele. METHOD: From participants in a nationwide, multicenter,
      hospital-based cohort study of dementia by the Clinical Research Center for
      Dementia of South Korea (November 2005 to December 2011), data for 5,077 elderly
      subjects (mean [SD] age = 71.37 [8.40] years) who had available data for APOE
      genotype and WMH severity were studied retrospectively. We used the diagnostic
      criteria for mild cognitive impairment proposed by Petersen et al; the diagnostic
      criteria for vascular dementia included in DSM-IV; and, for probable Alzheimer's
      disease, the criteria issued by the National Institute of Neurological and
      Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders
      Association. WMH severity was evaluated using modified criteria of Fazekas et al
      and Scheltens et al using T2 axial or fluid-attenuated inversion recovery
      magnetic resonance images, yielding 3 groups for WMH severity level. APOE
      genotype was determined by analysis of venous blood, and all participants were
      classified into 2 groups depending on presence or absence of the APOE epsilon4
      allele. The Seoul Neuropsychological Screening Battery-Dementia Version was used
      for all subjects. Cognitive impairment, classified by 6 cognitive test scores,
      was the primary outcome measure. Using multiple logistic regression, we
      investigated which cognitive domains were associated with WMH severity and the
      APOE epsilon4 allele, and, using analysis of covariance, we examined the
      interaction effects of these 2 factors on cognitive test scores. RESULTS: After
      multivariable adjustments, logistic regression analyses showed that WMH severity
      was associated with higher odds of cognitive impairment on frontal/executive
      function tests in both APOE epsilon4 carriers (odds ratio [OR] = 2.49; 95% CI,
      1.65-3.76) and noncarriers (OR = 2.36; 95% CI, 1.83-3.03). WMH severity was not
      significantly associated with memory function in APOE epsilon4 carriers: for
      verbal memory, epsilon4 noncarriers had an OR of 1.44 (95% CI, 1.13-1.84), and
      epsilon4 carriers had an OR of 1.36 (95% CI, 0.87-2.04); for visuospatial memory,
      epsilon4 noncarriers had an OR of 1.86 (95% CI, 1.45-2.37), and epsilon4 carriers
      had an OR of 1.35 (95% CI, 0.89-2.04). Moreover, a significant interaction effect
      between APOE epsilon4 and WMH severity was confirmed on memory tests by analysis
      of covariance (verbal memory: F = 3.40, P = .033; visuospatial memory: F = 8.49,
      P < .001). CONCLUSIONS: Severe WMHs appear to be predominantly associated with
      frontal/executive dysfunction, irrespective of APOE epsilon4 allele presence. WMH
      severity and APOE epsilon4 had an interactive effect on memory function, with WMH
      severity affecting memory impairment only in APOE epsilon4 noncarriers.

PMID- 23146134
TI  - Novel wine yeast with mutations in YAP1 that produce less acetic acid during
      fermentation.
AB  - Acetic acid, a byproduct formed during yeast alcoholic fermentation, is the main
      component of volatile acidity (VA). When present in high concentrations in wine,
      acetic acid imparts an undesirable 'vinegary' character that results in a
      significant reduction in quality and sales. Previously, it has been shown that
      sake yeast strains resistant to the antifungal cerulenin produce significantly
      lower levels of VA. In this study, we used a classical mutagenesis method to
      isolate a series of cerulenin-resistant strains, derived from a commercial
      diploid wine yeast. Four of the selected strains showed a consistent low-VA
      production phenotype after small-scale fermentation of different white and red
      grape musts. Specific mutations in YAP1, a gene encoding a transcription factor
      required for oxidative stress tolerance, were found in three of the four low-VA
      strains. When integrated into the genome of a haploid wine strain, the mutated
      YAP1 alleles partially reproduced the low-VA production phenotype of the diploid
      cerulenin-resistant strains, suggesting that YAP1 might play a role in
      (regulating) acetic acid production during fermentation. This study offers
      prospects for the development of low-VA wine yeast starter strains that could
      assist winemakers in their effort to consistently produce wine to definable
      quality specifications.

PMID- 23146137
TI  - Immunological basis of melanoma-associated vitiligo-like depigmentation.
AB  - Vitiligo is a skin condition characterized by white, hypopigmented macules.
      Melanocyte loss is a feature of the disease, and it has been hypothesized that an
      autoimmune mechanism could be responsible for the depigmentation. Melanoma is a
      malignancy that develops in melanocytes; if not detected and treated early, it is
      often deadly. Leukoderma, a condition characterized by depigmentation of the
      skin, is sometimes associated with malignant melanoma. An immune response against
      melanocyte antigens leading to destruction of either melanoma cells or
      melanocytes has been observed in both vitiligo and melanoma. Studies in animal
      models and humans have shown that humoral and cell-mediated immune responses are
      involved in modulating cytotoxic activity against tumor cells and normal
      melanocytes. The study of factors associated with anti-tumor immunopathogenic
      mechanisms -autoimmunity for example- may provide us with tools for the diagnosis
      and treatment of diseases such as vitiligo and malignant melanoma. 

PMID- 23146135
TI  - Effects of growth hormone withdrawal in obese premenopausal women.
AB  - OBJECTIVE: We previously reported improved body composition and cardiovascular
      risk markers plus a small decrease in glucose tolerance with GH administration vs
      placebo for 6 months to abdominally obese premenopausal women. The objective of
      this study was to determine whether the effects of GH treatment on cardiovascular
      risk markers, body composition and glucose tolerance in obese women persist 6
      months after GH withdrawal. DESIGN AND PATIENTS: Fifty abdominally obese
      premenopausal women completed a trial of rhGH vs placebo for 6 months; thirty
      nine women completed a subsequent 6-month withdrawal observation period.
      MEASUREMENTS: IGF-I, body composition by CT, (1) H-MRS and DXA, serum
      cardiovascular risk markers, oral glucose tolerance test (OGTT). RESULTS: IGF-I
      standard deviation scores (SDS) within the GH group were -1.7 +/- 0.1
      (pretreatment),-0.1 +/- 0.3 (after 6 months of GH) and -1.7 +/- 0.1 (6 months
      post-GH withdrawal). Six months after GH withdrawal, total abdominal and
      subcutaneous adipose tissue, total fat, trunk fat, trunk/extremity fat, hsCRP,
      apoB, LDL, and tPA were higher than at the 6-month (GH discontinuation) timepoint
      (P <= 0.05). All body composition and cardiovascular risk markers that had
      improved with GH returned to baseline levels by 6 months after GH
      discontinuation, as did fasting and 2-h OGTT glucose levels. CONCLUSION: The
      effects of GH administration to abdominally obese premenopausal women have a
      short time-course. The beneficial effects on body composition and cardiovascular
      risk markers, and the side effect of altered glucose tolerance returned to
      pretreatment levels after GH withdrawal. There was no suppression of endogenous
      IGF-I levels, which returned to baseline after GH withdrawal.

PMID- 23146138
TI  - Optimising the location of antenatal classes.
AB  - OBJECTIVES: To combine microsimulation and location-allocation techniques to
      determine antenatal class locations which minimise the distance travelled from
      home by potential users. DESIGN: Microsimulation modeling and location-allocation
      modeling. SETTING: City of Leeds, UK. PARTICIPANTS: Potential users of antenatal
      classes. METHODS: An individual-level microsimulation model was built to estimate
      the number of births for small areas by combining data from the UK Census 2001
      and the Health Survey for England 2006. Using this model as a proxy for service
      demand, we then used a location-allocation model to optimize locations. FINDINGS:
      Different scenarios show the advantage of combining these methods to optimize
      (re)locating antenatal classes and therefore reduce inequalities in accessing
      services for pregnant women. KEY CONCLUSIONS: Use of these techniques should lead
      to better use of resources by allowing planners to identify optimal locations of
      antenatal classes which minimise women's travel. IMPLICATIONS FOR PRACTICE: These
      results are especially important for health-care planners tasked with the
      difficult issue of targeting scarce resources in a cost-efficient, but also
      effective or accessible, manner. (169 words).

PMID- 23146139
TI  - The relationship between the use of the partograph and birth outcomes at Korle-Bu
      teaching hospital.
AB  - OBJECTIVE: maternal mortality represents the single greatest health disparity
      between high and low income countries. This inequity is especially felt in low
      income countries in sub Saharan Africa and Southeast Asia where 99% of the global
      burden of maternal death is borne. A goal of MDG 5 is to reduce maternal
      mortality and have a skilled attendant at every birth by 2015. A critical skill
      is ongoing intrapartum monitoring of labour progress and maternal/fetal well
      being. The WHO partograph was designed to assess these parameters. DESIGN AND
      SETTING: a retrospective review of charts (n=1,845) retrieved consecutively over
      a 2 month period in a tertiary teaching hospital in Ghana was conducted to assess
      the adequacy of partograph use by skilled birth attendants and the timeliness of
      action taken if the action line was crossed. WHO guidelines were implemented to
      assess the adequacy of partograph use and how this affected maternal neonatal
      outcomes. Further, the timeliness and type of action taken if action line was
      crossed was assessed. FINDINGS: partographs were adequately completed in
      accordance with WHO guidelines only 25.6% (472) of the time and some data
      appeared to be entered retrospectively. Partograph use was associated with less
      maternal blood loss and neonatal injuries. When the action line was crossed
      (464), timely action was taken only 48.7% of the time and was associated with
      less assisted delivery and a fewer low Apgar scores and NICU admissions.
      CONCLUSION: when adequately used and timely interventions taken, the partograph
      was an effective tool. Feasibility of partograph use requires more scrutiny;
      particularly identification of minimum frequency for safe monitoring and key
      variables as well as a better understanding of why skilled attendants have not
      consistently 'bought in' to partograph use. Frontline workers need access to
      ongoing and current education and strategically placed algorhythims.

PMID- 23146140
TI  - Keeping baby SAFE in pregnancy: evaluating the brochure.
AB  - OBJECTIVE: to gain a better understanding of women's baseline level of knowledge
      of stillbirth and determine whether giving written information during pregnancy
      results in improvement in knowledge about stillbirth. DESIGN: a pre-post
      intervention study. SETTING: women undergoing antenatal care at a small maternity
      hospital were asked, via questionnaire, about their knowledge of stillbirth both
      before and after reading an information brochure on the subject. PARTICIPANTS: 22
      pregnant women who were in the last trimester of pregnancy. RESULTS: a
      statistically significant increase in knowledge was evident in awareness of the
      incidence in stillbirth (p<0.001). Women also were more aware of some of the
      proactive things they could do to prevent this tragedy from occurring to them.
      This improvement in understanding may be attributed to reading the brochure.
      DISCUSSION: prior to reading the brochure all women understood the term
      'stillbirth' but most lacked knowledge pertinent to understanding how often it
      occurs. The most significant difference noted between the pre- and post
      intervention analysis was the improvement in women's knowledge of the incidence
      of stillbirth. Further to this, prior to reading the brochure most women were
      unaware of action they themselves could take to reduce risk such as awareness of
      fetal movements, whereas after reading the brochure this was more likely to be
      cited. CONCLUSIONS: the results from this pilot study may indicate that a
      specifically designed information brochure explaining the incidence of stillbirth
      in plain language could enhance pregnant women's knowledge. This area of study
      warrants further investigation, especially as to whether such knowledge is of an
      enduring nature or whether awareness results in reduced incidence.

PMID- 23146141
TI  - Applying a social disparities lens to obesity in pregnancy to inform efforts to
      intervene.
AB  - OBJECTIVE: to examine the social correlates of pre-pregnancy overweight and
      obesity in an Australian population-based sample and consider implications for
      intervention effectiveness during pregnancy. DESIGN: population-based survey
      distributed by hospitals to women 6 months after birth. SETTING: two states of
      Australia. PARTICIPANTS: women who gave birth in Victoria and South Australia in
      September/October 2007. MEASUREMENTS AND FINDINGS: surveys were completed by
      4,366 women. Pre-pregnancy body mass index (BMI) was calculated from women's self
      reported weight in kilograms/(height in metres)(2). Results showed high rates of
      overweight (22%) and obesity (14%) among Australian women entering pregnancy.
      After adjusting for other factors in the model, pre-pregnancy obesity was
      significantly associated with lower household income levels, less education, the
      experience of financial stress in pregnancy and increasing parity. KEY
      CONCLUSIONS: to date, there is little evidence to support the efficacy of
      interventions to manage problematic weight in pregnancy. Applying a social
      disparities lens to obesity in pregnancy challenges us to consider social factors
      that may seem distal to obesity but are highly relevant to efficacious
      intervention. IMPLICATIONS FOR PRACTICE: pregnancy care offers an opportunity to
      address social issues on the pathway to obesity. Current clinical care guidelines
      on maternal overweight and obesity in pregnancy rarely consider social contexts
      that place some women at risk and are a likely impediment to efficacious
      intervention.

PMID- 23146142
TI  - Aberrant gene expression patterns in extraembryonic tissue from cloned porcine
      embryos.
AB  - The abnormal development of embryos reconstructed by somatic cell nuclear
      transfer (SCNT) is considered to be associated with consequent changes in gene
      expression following errors in epigenetic reprogramming. In this study, we
      carried out SCNT using donor fibroblast cells derived from 3-way hybrids
      (Landrace*Duroc*Yorkshire). A total of 655 SCNT embryos were transferred, and
      6.97+/-2.3 cloned fetuses were successfully recovered from three surrogates at
      gestational day 30. An analysis of the 6.97+/-2.3 cloned embryos revealed that
      most had severe extraembryonic defects. The extraembryonic tissue from the SCNT
      embryos was abnormally small compared with that of the control. To investigate
      the differentially expressed genes between the SCNT and control extraembryonic
      tissues, we compared the gene expression profiles of the extraembryonic tissues
      from gestational day 30 cloned pig embryos with those from the control using an
      annealing control primer-based GeneFishing polymerase chain reaction. As a
      result, we found that a total of 50 genes were differentially expressed by
      utilizing 120 ACPs, 38 genes of which were known. Among them, 26 genes were up
      regulated, whereas 12 genes were down-regulated. Real-time RT-PCR showed that
      apoptosis-related genes were expressed significantly higher in SCNT
      extraembryonic tissue than in the control, whereas metabolism-related genes were
      expressed at significantly lower levels in the SCNT extraembryonic tissue. These
      observations strongly indicate that early gestational death of SCNT embryo is
      caused, at least in part, by the disruption of developing extraembryonic tissues
      as a result of aberrant gene expression, which results in abnormal apoptosis and
      metabolism.

PMID- 23146143
TI  - Use of response surface methodology for development of new microwell-based
      spectrophotometric method for determination of atrovastatin calcium in tablets.
AB  - BACKGROUND: Response surface methodology by Box-Behnken design employing the
      multivariate approach enables substantial improvement in the method development
      using fewer experiments, without wastage of large volumes of organic solvents,
      which leads to high analysis cost. This methodology has not been employed for
      development of a method for analysis of atorvastatin calcium (ATR-Ca). RESULTS:
      The present research study describes the use of in optimization and validation of
      a new microwell-based UV-Visible spectrophotometric method of for determination
      of ATR-Ca in its tablets. By the use of quadratic regression analysis, equations
      were developed to describe the behavior of the response as simultaneous functions
      of the selected independent variables. Accordingly, the optimum conditions were
      determined which included concentration of 2,3-dichloro-5,6-dicyano-1,4
      benzoquinone (DDQ), time of reaction and temperature. The absorbance of the
      colored-CT complex was measured at 460 nm by microwell-plate absorbance reader.
      The method was validated, in accordance with ICH guidelines for accuracy,
      precision, selectivity and linearity (r2 = 0.9993) over the concentration range
      of 20-200 MUg/ml. The assay was successfully applied to the analysis of ATR-Ca in
      its pharmaceutical dosage forms with good accuracy and precision. CONCLUSION: The
      assay described herein has great practical value in the routine analysis of ATR
      Ca in quality control laboratories, as it has high throughput property, consumes
      minimum volume of organic solvent thus it offers the reduction in the exposures
      of the analysts to the toxic effects of organic solvents, environmentally
      friendly "Green" approach) and reduction in the analysis cost by 50-fold.

PMID- 23146144
TI  - Accuracy of pedigree and genomic predictions of carcass and novel meat quality
      traits in multi-breed sheep data assessed by cross-validation.
AB  - BACKGROUND: Genomic predictions can be applied early in life without impacting
      selection candidates. This is especially useful for meat quality traits in sheep.
      Carcass and novel meat quality traits were predicted in a multi-breed sheep
      population that included Merino, Border Leicester, Polled Dorset and White
      Suffolk sheep and their crosses. METHODS: Prediction of breeding values by best
      linear unbiased prediction (BLUP) based on pedigree information was compared to
      prediction based on genomic BLUP (GBLUP) and a Bayesian prediction method
      (BayesR). Cross-validation of predictions across sire families was used to
      evaluate the accuracy of predictions based on the correlation of predicted and
      observed values and the regression of observed on predicted values was used to
      evaluate bias of methods. Accuracies and regression coefficients were calculated
      using either phenotypes or adjusted phenotypes as observed variables. RESULTS AND
      CONCLUSIONS: Genomic methods increased the accuracy of predicted breeding values
      to on average 0.2 across traits (range 0.07 to 0.31), compared to an average
      accuracy of 0.09 for pedigree-based BLUP. However, for some traits with smaller
      reference population size, there was no increase in accuracy or it was small. No
      clear differences in accuracy were observed between GBLUP and BayesR. The
      regression of phenotypes on breeding values was close to 1 for all methods,
      indicating little bias, except for GBLUP and adjusted phenotypes (regression =
      0.78). Accuracies calculated with adjusted (for fixed effects) phenotypes were
      less variable than accuracies based on unadjusted phenotypes, indicating that
      fixed effects influence the latter. Increasing the reference population size
      increased accuracy, indicating that adding more records will be beneficial. For
      the Merino, Polled Dorset and White Suffolk breeds, accuracies were greater than
      for the Border Leicester breed due to the smaller sample size and limited across
      breed prediction. BayesR detected only a few large marker effects but one region
      on chromosome 6 was associated with large effects for several traits. Cross
      validation produced very similar variability of accuracy and regression
      coefficients for BLUP, GBLUP and BayesR, showing that this variability is not a
      property of genomic methods alone. Our results show that genomic selection for
      novel difficult-to-measure traits is a feasible strategy to achieve increased
      genetic gain.

PMID- 23146145
TI  - Size-dependent antimicrobial properties of sugar-encapsulated gold nanoparticles
      synthesized by a green method.
AB  - The antimicrobial properties of dextrose-encapsulated gold nanoparticles (dGNPs)
      with average diameters of 25, 60, and 120 nm (+/- 5) and synthesized by green
      chemistry principles were investigated against both Gram-negative and Gram
      positive bacteria. Studies were performed involving the effect of dGNPs on the
      growth, morphology, and ultrastructural properties of bacteria. dGNPs were found
      to have significant dose-dependent antibacterial activity which was also
      proportional to their size. Experiments revealed the dGNPs to be bacteriostatic
      as well as bactericidal. The dGNPs exhibited their bactericidal action by
      disrupting the bacterial cell membrane which leads to the leakage of cytoplasmic
      content. The overall outcome of this study suggests that green-synthesized dGNPs
      hold promise as a potent antibacterial agent against a wide range of disease
      causing bacteria by preventing and controlling possible infections or diseases.

PMID- 23146146
TI  - On the HORYZON: moderated online social therapy for long-term recovery in first
      episode psychosis.
AB  - BACKGROUND: Early intervention services have demonstrated improved outcomes in
      first episode psychosis (FEP); however, recent evidence shows that treatment
      benefits may not be sustainable over time. These findings have resulted in
      repeated recommendations for the implementation of longer term treatment
      programs. An Internet-based intervention specifically designed for young people
      with psychosis may provide a cost-effective alternative to prevent loss of
      treatment benefits from early intervention. METHODS: Our multi-disciplinary team
      has developed a highly novel online intervention (HORYZONS) in regular
      consultation with stakeholders within a specialist early psychosis program.
      HORYZONS integrates: i) peer-to-peer social networking, ii) individually tailored
      interactive psychosocial interventions, and iii) expert interdisciplinary and
      peer-moderation in a coherent platform designed to improve long-term outcomes in
      FEP. The acceptability, safety and initial clinical benefits of HORYZONS were
      examined through a 1-month pilot study with 20 participants with FEP. RESULTS:
      There were no dropouts during the pilot study. Seventy per cent of participants
      utilised the system for at least 3weeks, 95% used the social networking features,
      and 60% completed at least 3 therapy modules. System usage was high during the
      study. There were no incidents and the majority of participants reported feeling
      safe, empowered and more socially connected using HORYZONS. Analysis revealed a
      significant reduction in depressive symptoms at follow-up. CONCLUSIONS: Our
      results indicate that HORYZONS is feasible, engaging and safe and may augment
      social connectedness and empowerment in FEP. These findings have significant
      implications for the enhancement of specialist FEP services. The potential of
      HORYZONS to improve long-term recovery is worthy of further investigation.

PMID- 23146147
TI  - A method for directly correlating site-specific cross-sectional and plan-view
      transmission electron microscopy of individual nanostructures.
AB  - A sample preparation method is described for enabling direct correlation of site
      specific plan-view and cross-sectional transmission electron microscopy (TEM)
      analysis of individual nanostructures by employing a dual-beam focused-ion beam
      (FIB) microscope. This technique is demonstrated using Si nanowires dispersed on
      a TEM sample support (lacey carbon or Si-nitride). Individual nanowires are first
      imaged in the plan-view orientation to identify a region of interest; in this
      case, impurity atoms distributed at crystalline defects that require further
      investigation in the cross-sectional orientation. Subsequently, the region of
      interest is capped with a series of ex situ and in situ deposited layers to
      protect the nanowire and facilitate site-specific lift-out and cross-sectioning
      using a dual-beam FIB microscope. The lift-out specimen is thinned to electron
      transparency with site-specific positioning to within ~ 200 nm of a target
      position along the length of the nanowire. Using the described technique, it is
      possible to produce correlated plan-view and cross-sectional view lattice
      resolved TEM images that enable a quasi-3D analysis of crystalline defect
      structures in a specific nanowire. While the current study is focused on
      nanowires, the procedure described herein is general for any electron-transparent
      sample and is broadly applicable for many nanostructures, such as nanowires,
      nanoparticles, patterned thin films, and devices.

PMID- 23146148
TI  - Electrophysiological and motor function scale association in a pre-symptomatic
      infant with spinal muscular atrophy type I.
AB  - A term infant, at familial risk for spinal muscular atrophy (SMA), had the
      diagnosis genetically confirmed on day 3 of life. Clinical evaluation, the CHOP
      INTEND motor scale and the CMAP amplitude were obtained on days 5 (pre
      symptomatic), 20 (mildly weak), 34 (moderately weak) and 63 (severely weak).
      Palliative care was provided and he expired of an acute pulmonary infection on
      day 81. The CMAP amplitude and INTEND scores were initially in the normal range,
      then followed a corresponding decline to a nadir at day 34 and remained so at the
      4th assessment. A log-transformed plot of CMAP amplitude from days 5-34 was
      linear. These data suggest that early motor neuron loss in SMA type I may be
      logarithmic and demonstrates that the INTEND motor scale closely follows the CMAP
      electrophysiological biomarker. This single case report supports the
      consideration that early intervention with a potential therapy is necessary,
      before the pool of functional motor neurons has plummeted. Further study of these
      parameters in pre-symptomatic infants with SMA type I will help guide the design
      of future intervention studies.

PMID- 23146149
TI  - Nanoscale imaging of the Candida-macrophage interaction using correlated
      fluorescence-atomic force microscopy.
AB  - Knowledge of the molecular bases underlying the interaction of fungal pathogens
      with immune cells is critical to our understanding of fungal infections and
      offers exciting perspectives for controlling immune responses for therapy.
      Although fluorescence microscopy is a valuable tool to visualize pathogen-host
      interactions, the spatial resolution is low, meaning the fine structural details
      of the interacting cells cannot be observed. Here, we demonstrate the ability of
      correlated fluorescence-atomic force microscopy (AFM) to image the various steps
      of the interaction between fungal pathogens and macrophages with nanoscale
      resolution. We focus on Candida albicans, known to grow as two morphological
      forms (yeast cells, filamentous hyphae) that play important roles in modulating
      the interaction with macrophages. We observe the main steps of macrophage
      infection, including initial intercellular contact, phagocytosis by
      internalization of yeast cells, intracellular hyphal growth leading to mechanical
      stretching, and piercing of the macrophage membrane resulting in pathogen escape.
      While fluorescence imaging clearly distinguishes fungal cells from macrophages
      during the various steps of the process, AFM captures nanoscale structural
      features of the macrophage surface that are of high biological relevance,
      including ruffles, lamellipodia, filopodia, membrane remnants, and phagocytic
      cups. As fungal pathogenesis is mainly controlled by the ability of fungi to
      escape from immune cells, the nanoimaging platform established here has great
      potential in nanomedicine for understanding and controlling fungal infections.

PMID- 23146150
TI  - Oral scopolamine augmentation in moderate to severe major depressive disorder: a
      randomized, double-blind, placebo-controlled study.
AB  - OBJECTIVE: To evaluate the antidepressant effect of oral scopolamine as an
      adjunct to citalopram. METHOD: In this randomized double-blind placebo-controlled
      study, patients were assessed in the outpatient clinics of 2 large hospitals from
      November 2011 to January 2012. Forty patients (18-55 years) with major depressive
      disorder (DSM-IV-TR criteria) and 17-Item Hamilton Depression Rating Scale (HDRS)
      score >= 22 were randomly assigned to scopolamine hydrobromide (1 mg/d) (n = 20)
      or placebo (n = 20) in addition to citalopram for 6 weeks. HDRS score was
      measured at baseline and days 4, 7, 14, 28, and 42. The primary outcome measure
      was HDRS score change from baseline to week 6 in the scopolamine group versus the
      placebo group. Response was defined as >= 50% decrease in HDRS score; remission,
      as HDRS score <= 7. RESULTS: Augmentation with scopolamine was significantly more
      effective than placebo (F(1,38) = 5.831, P = .021). Patients receiving
      scopolamine showed higher rates of response (65%, 13/20 at week 4) and remission
      (65%, 13/20 at week 6) than the placebo group (30%, 6/20 and 20%, 4/20,
      respectively; P = .027, P = .004, respectively). Patients in the scopolamine
      group showed higher rates of dry mouth, blurred vision, and dizziness than the
      placebo group. CONCLUSIONS: Oral scopolamine is a safe and effective adjunct for
      treatment of patients with moderate to severe major depressive disorder. TRIAL
      REGISTRATION: Iranian Registry of Clinical Trials identifier:
      IRCT201201181556N31.

PMID- 23146151
TI  - Nintedanib (BIBF 1120) for IPF: a tomorrow therapy?
AB  - Idiopathic pulmonary fibrosis is a rare, life threatening disease characterized
      by an anarchic fibrogenesis, limited survival and few therapeutic options. Its
      pathogenesis is complex and involves the interaction among various pathways
      driven by proinflammatory/profibrogenetic mediators such as platelet -derived
      growth factor, vascular endothelial growth factor or basic fibroblast growth
      factor. Given their prominent pathogenic roles in this disease such growth factor
      might be suitable therapeutic targets.In fact, the existing preclinical and
      clinical data demonstrated that their therapeutic inhibition results in a delayed
      progression of the pulmonary fibrosis and in the improvement of the disease
      outcome. BIBF 1120 is a potent triple blocker of the receptors of these growth
      factors which is currently evaluated as a potential therapy in the idiopathic
      pulmonary fibrosis. This review discusses the existing data supporting its
      potential use in this disease.

PMID- 23146152
TI  - Functional specialization of duplicated AP3-like genes in Medicago truncatula.
AB  - The B-class of MADS box genes has been studied in a wide range of plant species,
      but has remained largely uncharacterized in legumes. Here we investigate the
      evolutionary fate of the duplicated AP3-like genes of a legume species. To obtain
      insight into the extent to which B-class MADS box gene functions are conserved or
      have diversified in legumes, we isolated and characterized the two members of the
      AP3 lineage in Medicago truncatula: MtNMH7 and MtTM6 (euAP3 and paleoAP3 genes,
      respectively). A non-overlapping and complementary expression pattern of both
      genes was observed in petals and stamens. MtTM6 was expressed predominantly in
      the outer cell layers of both floral organs, and MtNMH7 in the inner cell layers
      of petals and stamens. Functional analyses by reverse genetics approaches (RNAi
      and Tnt1 mutagenesis) showed that the contribution of MtNMH7 to petal identity is
      more important than that of MtTM6, whereas MtTM6 plays a more important role in
      stamen identity than its paralog MtNMH7. Our results suggest that the M.
      truncatula AP3-like genes have undergone a functional specialization process
      associated with complete partitioning of gene expression patterns of the
      ancestral gene lineage. We provide information regarding the similarities and
      differences in petal and stamen development among core eudicots.

PMID- 23146153
TI  - Infective endocarditis on a percutaneous prosthetic aortic valve with associated
      glomerulopathy due to Granulicatella adjacens.

PMID- 23146154
TI  - Hyponatremia, acute kidney injury, and mortality in HIV-related toxoplasmic
      encephalitis.
AB  - BACKGROUND: There are no reports on hyponatremia and acute kidney injury (AKI)
      involved in the course of HIV-related toxoplasmic encephalitis (TE). The main
      objective of this study was to describe the occurrence of hyponatremia and its
      relationship with AKI and mortality in HIV-related toxoplasmic encephalitis (TE).
      METHODS: This was a retrospective cohort study on patients with HIV-related TE.
      AKI was considered only when the RIFLE (risk, injury, failure, loss, end-stage)
      criterion was met, after the patient was admitted. RESULTS: A total of 92
      patients were included, with a mean age of 36+/-9 years. Hyponatremia at
      admission was observed in 43 patients (46.7%), with AKI developing in 25 (27.1%)
      patients during their hospitalization. Sulfadiazine was the treatment of choice
      in 81% of the cases. Death occurred in 13 cases (14.1%). Low serum sodium level
      correlated directly with AKI and mortality. Male gender (OR 7.89, 95% CI 1.22
      50.90, p = 0.03) and hyponatremia at admission (OR 4.73, 95% CI 1.22-18.30, p =
      0.02) were predictors for AKI. Independent risk factors for death were AKI (OR
      8.3, 95% CI 1.4-48.2, p < 0.0001) and hyponatremia (OR 9.9, 95% CI 1.2-96.3, p <
      0.0001). CONCLUSION: AKI and hyponatremia are frequent in TE. Hyponatremia on
      admission is highly associated with AKI and mortality.

PMID- 23146155
TI  - Desmodus rotundus and Artibeus spp. bats might present distinct rabies virus
      lineages.
AB  - In Brazil, bats have been assigned an increasing importance in public health as
      they are important rabies reservoirs. Phylogenetic studies have shown that rabies
      virus (RABV) strains from frugivorous bats Artibeus spp. are closely associated
      to those from the vampire bat Desmodus rotundus, but little is known about the
      molecular diversity of RABV in Artibeus spp. The N and G genes of RABV isolated
      from Artibeus spp. and cattle infected by D. rotundus were sequenced, and
      phylogenetic trees were constructed. The N gene nucleotides tree showed three
      clusters: one for D. rotundus and two for Artibeus spp. Regarding putative N
      amino acid-trees, two clusters were formed, one for D. rotundus and another for
      Artibeus spp. RABV G gene phylogeny supported the distinction between D. rotundus
      and Artibeus spp. strains. These results show the intricate host relationship of
      RABV's evolutionary history, and are invaluable for the determination of RABV
      infection sources.

PMID- 23146156
TI  - Brain gene expression differences are associated with abnormal tail biting
      behavior in pigs.
AB  - Knowledge about gene expression in animals involved in abnormal behaviors can
      contribute to the understanding of underlying biological mechanisms. This study
      aimed to explore the motivational background to tail biting, an abnormal
      injurious behavior and severe welfare problem in pig production. Affymetrix
      microarrays were used to investigate gene expression differences in the
      hypothalamus and prefrontal cortex of pigs performing tail biting, pigs receiving
      bites to the tail and neutral pigs who were not involved in the behavior. In the
      hypothalamus, 32 transcripts were differentially expressed (P < 0.05) when tail
      biters were compared with neutral pigs, 130 when comparing receiver pigs with
      neutrals, and two when tail biters were compared with receivers. In the
      prefrontal cortex, seven transcripts were differently expressed in tail biters
      when compared with neutrals, seven in receivers vs. neutrals and none in the tail
      biters vs. receivers. In total, 19 genes showed a different expression pattern in
      neutral pigs when compared with both performers and receivers. This implies that
      the functions of these may provide knowledge about why the neutral pigs are not
      involved in tail biting behavior as performers or receivers. Among these 19
      transcripts were genes associated with production traits in pigs (PDK4),
      sociality in humans and mice (GTF2I) and novelty seeking in humans (EGF). These
      are in line with hypotheses linking tail biting with reduced back fat thickness
      and explorative behavior.

PMID- 23146157
TI  - Valence atom with bohmian quantum potential: the golden ratio approach.
AB  - BACKGROUND: The alternative quantum mechanical description of total energy given
      by Bohmian theory was merged with the concept of the golden ratio and its
      appearance as the Heisenberg imbalance to provide a new density-based description
      of the valence atomic state and reactivity charge with the aim of clarifying
      their features with respect to the so-called DFT ground state and critical
      charge, respectively. RESULTS: The results, based on the so-called double
      variational algorithm for chemical spaces of reactivity, are fundamental and,
      among other issues regarding chemical bonding, solve the existing paradox of
      using a cubic parabola to describe a quadratic charge dependency. CONCLUSIONS:
      Overall, the paper provides a qualitative-quantitative explanation of chemical
      reactivity based on more than half of an electronic pair in bonding, and provide
      new, more realistic values for the so-called "universal" electronegativity and
      chemical hardness of atomic systems engaged in reactivity (analogous to the atoms
      in-molecules framework).

PMID- 23146159
TI  - How does a xylem-feeder maximize its fitness?
AB  - The current case study concerns evaluation of the life history of an insect
      species living in a demanding habitat, namely a xylem-feeder Aredolpona rubra
      (Linnaeus) (Coleoptera: Cerambycidae) representing the wood-feeding guild. Growth
      rate, development time and body size at maturity were studied at different
      temperature regimes with discreteness of insect growth pattern, associated with
      moultings, taken into account. Moreover, the temperature effect on reproductive
      strategy of females was tested, and the general life history was compared with
      available data within the wood-feeding guild. The results show that: (i) the
      growth of A. rubra is slow but compensated by prolonged development; (ii) size
      dimorphism is probably caused by the longer development time of females; (iii)
      fecundity is at least partly determined by the temperature experienced during the
      egg-laying period; and (iv) interspecific comparisons reveal that the life
      strategy of a wood-feeder depends on the niche occupied within the tree, whilst
      its breeding strategy (whether capital or income) is controlled at a taxonomic
      level. Control of all the main life history traits at one time provided a unique
      opportunity to understand the selection pressures on A. rubra species. Moreover,
      comparison within a feeding guild broadens this context and identifies the
      sources of heterogeneity in the 'inside-wood' habitat. The knowledge so gathered
      may be applied to pest control in forestry science, as well as to the
      conservation of rare and endangered insect species living within trees.

PMID- 23146158
TI  - Repairing chronic myocardial infarction with autologous mesenchymal stem cells
      engineered tissue in rat promotes angiogenesis and limits ventricular remodeling.
AB  - BACKGROUND: Tissue engineering scaffold constitutes a new strategy of myocardial
      repair. Here, we studied the contribution of a patch using autologous mesenchymal
      stem cells (MSCs) seeded on collagen-1 scaffold on the cardiac reconstruction in
      rat model of chronic myocardial infarction (MI). METHODS: Patches were cultured
      with controlled MSCs (growth, phenotype and potentiality). Twenty coronary
      ligated rats with tomoscingraphy (SPECT)-authenticated transmural chronic MI were
      referred into a control group (n = 10) and a treated group (n = 10) which
      beneficiated an epicardial MSC-patch engraftment. Contribution of MSC-patch was
      tested 1-mo after using non-invasive SPECT cardiac imaging, invasive hemodynamic
      assessment and immunohistochemistry. RESULTS: 3D-collagen environment affected
      the cell growth but not the cell phenotype and potentiality. MSC-patch integrates
      well the epicardial side of chronic MI scar. In treated rats, one-month SPECT
      data have documented an improvement of perfusion in MI segments compared to
      control (64 +/- 4% vs 49 +/- 3% p = 0.02) and a reduced infarction. Contractile
      parameter dp/dtmax and dp/dtmin were improved (p & 0.01). Histology showed an
      increase of ventricular wall thickness (1.75 +/- 0.24 vs 1.35 +/- 0.32 mm, p
      &0.05) and immunochemistry of the repaired tissue displayed enhanced angiogenesis
      and myofibroblast-like tissue. CONCLUSION: 3D-MSC-collagen epicardial patch
      engraftment contributes to reverse remodeling of chronic MI.

PMID- 23146160
TI  - Age-dependent changes in the ratio of (R)- and (S)-2-butanol released by virgin
      females of Dasylepida ishigakiensis (Coleoptera: Scarabaeidae).
AB  - The females of the white grub beetle, Dasylepida ishigakiensis, release two
      enantiomers of 2-butanol, (R)-2-butanol and (S)-2-butanol. The ratio describing
      the relative proportions of these two enantiomers (R/S ratio) has not yet been
      investigated. (R)-2-Butanol has been shown to attract males in laboratory and
      field experiments, whereas (S)-2-butanol tends to inhibit them. To determine the
      R/S ratio of the 2-butanol emitted by virgin females, we collected 2-butanol from
      young (53 days old), mature (63 days old) and old females (73 days old) using
      water, extracted with an SPME fibre and subsequently injected into GC-MS. The
      major component of the 2-butanol emitted by the young females was (R)-2-butanol,
      but as the females aged, the component ratio favoured (S)-2-butanol. Young
      females released an 80:20 mixture of (R)- and (S)-2-butanol, whereas old females
      released a 45:55 mixture. The EAG response of male antennae to a 50:50 ratio
      (racemic mixture) showed a similar dose-response curve to that of (R)-2-butanol.
      The male orientation responses to (R)-2-butanol decreased when the relative
      proportion of (S)-2-butanol increased. An inhibitory and/or masking effect of (S)
      2-butanol on male orientation behaviour was also observed in the flight tunnel
      assay. These results suggest that males are more strongly attracted to young
      females than to old females. We also discuss the possibility of using 2-butanol
      isomers as a control or monitoring agent for this insect.

PMID- 23146161
TI  - Abnormal patient, normal test: the otologist's dilemma.

PMID- 23146162
TI  - A one-pot procedure for the preparation of N-9-fluorenylmethyloxycarbonyl-alpha
      amino diazoketones from alpha-amino acids.
AB  - The study describes a new "one-pot" route to the synthesis of N-9
      fluorenylmethyloxycarbonyl (Fmoc) alpha-amino diazoketones. The procedure was
      tested on a series of commercially available free or side-chain protected alpha
      amino acids employed as precursors. The conversion into the title compounds was
      achieved by masking and activating the alpha-amino acids with a single reagent,
      namely, 9-fluorenylmethyl chloroformate (Fmoc-Cl). The resulting N-protected
      mixed anhydrides were reacted with diazomethane to lead to the alpha-amino
      diazoketones, which were isolated by flash column chromatography in very good to
      excellent overall yields. The versatility of the procedure was verified on
      lipophilic alpha-amino acids and further demonstrated by the preparation of N
      Fmoc-alpha-amino diazoketones also from alpha-amino acids containing side-chain
      masking groups, which are orthogonal to the Fmoc one. The results confirmed that
      tert-butyloxycarbonyl (Boc), tert-butyl ((t)Bu), and 2,2,4,6,7
      pentamethyldihydrobenzofuran-5-sulfonyl (Pbf), three acid-labile protecting
      groups mostly adopted in the solution and solid-phase peptide synthesis, are
      compatible to the adopted reaction conditions. In all cases, the formation of the
      corresponding C-methyl ester of the starting amino acid was not observed.
      Moreover, the proposed method respects the chirality of the starting alpha-amino
      acids. No racemization occurred when the procedure was applied to the synthesis
      of the respective N-Fmoc-protected alpha-amino diazoketones from L-isoleucine and
      L-threonine and to the preparation of a diastereomeric pair of N-Fmoc-protected
      dipeptidyl diazoketones.

PMID- 23146163
TI  - Dental trauma, prevention and knowledge concerning dental first-aid among Polish
      amateur boxers.
AB  - OBJECTIVES: A significant increase in individuals participating in contact sports
      has been noticed. Boxing is one of the most traumatic of such sports. In spite of
      this, the level of awareness among young boxers as to prevention and dental first
      aid is very poor. The aim of this study was to evaluate the frequency of dental
      injuries during trainings and competitions, the habit of wearing mouthguards, and
      the general level of awareness regarding prevention and first aid after tooth
      avulsion. DESIGN: Cross-sectional survey. METHODS: Our research was based on
      questionnaires given to 338 amateur boxers in Poland (divided into age groups:
      schoolboys, juniors, youth and seniors). Chi-square tests were used for the
      comparison of groups of respondents and relevant variables. RESULTS: The survey
      showed that 35.9% of the participants had suffered some kind of dental trauma. A
      similar number of 36.5% had witnessed some kind of dental injury during training
      and 26.1% during tournaments. The survey showed that only 15.8% of all
      participants knew that immediate replantation was the best way of treating an
      avulsed tooth. Also, 93.7% of all those interviewed reported that they had worn
      mouth-formed mouthguards and only 5.7% custom-made mouthguards. Of all the
      survey's participants, 41.1% were definitely satisfied with their mouthguards.
      CONCLUSIONS: To improve knowledge regarding dental trauma in the boxing
      environment it is essential to emphasize the need for an extensive educational
      campaign. Preventive measures, especially in the form of good custom-made
      mouthguards, should be mandatory for all active individuals participating in
      contact sports.

PMID- 23146165
TI  - The current state of imaging pediatric genitourinary anomalies and abnormalities.
AB  - Genitourinary imaging has evolved along with the ever improving technology, in
      addition, our pattern of referrals has changed, with most neonates being
      presently asymptomatic and their examinations being prompted by prenatally
      detected abnormalities. Ultrasonography dominates in this domain because of the
      combination of the excellent demonstration of anatomy, lack of ionizing
      radiation, widespread availability, possibility for a dynamic examination,
      decreased need for sedation, and low cost. With faster sequences, magnetic
      resonance imaging plays an increasingly significant role predominantly with
      complex congenital anomalies because of its excellent delineation of anatomy as
      well as the absence of ionizing radiation. Fluoroscopic studies are also helpful
      to delineate the anatomy in certain cases and to identify connections between
      structures that may be present in congenital anomalies. This article reviews
      normal anatomy and congenital malformations of the genitourinary system.

PMID- 23146164
TI  - Hip and knee joint loading during vertical jumping and push jerking.
AB  - BACKGROUND: The internal joint contact forces experienced at the lower limb have
      been frequently studied in activities of daily living and rehabilitation
      activities. In contrast, the forces experienced during more dynamic activities
      are not well understood, and those studies that do exist suggest very high
      degrees of joint loading. METHODS: In this study a biomechanical model of the
      right lower limb was used to calculate the internal joint forces experienced by
      the lower limb during vertical jumping, landing and push jerking (an explosive
      exercise derived from the sport of Olympic weightlifting), with a particular
      emphasis on the forces experienced by the knee. FINDINGS: The knee experienced
      mean peak loadings of 2.4-4.6*body weight at the patellofemoral joint, 6.9
      9.0*body weight at the tibiofemoral joint, 0.3-1.4*body weight anterior tibial
      shear and 1.0-3.1*body weight posterior tibial shear. The hip experienced a mean
      peak loading of 5.5-8.4*body weight and the ankle 8.9-10.0*body weight.
      INTERPRETATION: The magnitudes of the total (resultant) joint contact forces at
      the patellofemoral joint, tibiofemoral joint and hip are greater than those
      reported in activities of daily living and less dynamic rehabilitation exercises.
      The information in this study is of importance for medical professionals, coaches
      and biomedical researchers in improving the understanding of acute and chronic
      injuries, understanding the performance of prosthetic implants and materials,
      evaluating the appropriateness of jumping and weightlifting for patient
      populations and informing the training programmes of healthy populations.

PMID- 23146166
TI  - Current role of multidetector computed tomography in imaging of wrist injuries.
AB  - Imaging of the wrist is challenging to both radiologists and orthopedic surgeons.
      This is primarily because of the complex anatomy/functionality of the wrist and
      also the fact that many frequent injuries are sustained to the hands. On going
      developments in multidetector computed tomography (MDCT) technology with its
      "state of the art" postprocessing capabilities have revolutionized this field.
      Apart from routine imaging of wrist trauma, it is now possible to assess
      intrinsic ligaments with MDCT arthrography, thereby avoiding invasive diagnostic
      arthroscopies. Postoperative wrist imaging can be a diagnostic challenge, and
      MDCT can be helpful in assessment of these cases because volume acquisition and
      excellent postprocessing abilities help to evaluate these wrists in any desired
      plane and thinner slices. This article pictorially reviews the current clinical
      role of MDCT imaging of wrist in our practice. It also describes arthrography
      technique and scanning parameters used at our center.

PMID- 23146167
TI  - Imaging of pediatric desmoplastic small-round-cell tumor with pathologic
      correlation.
AB  - Desmoplastic small-round-cell tumors are rare aggressive malignancies that belong
      to the "small round blue cell" tumor family. They predominantly affect the
      abdomen in adolescent and young adult males. Computed tomography is currently the
      modality of choice both for diagnosis and follow-up assessment. In this review,
      the authors provide a concise yet comprehensive discussion of this condition with
      emphasis on the imaging findings. Pathologic correlation, differential diagnostic
      considerations, and treatment will also be presented.

PMID- 23146168
TI  - Whole inactivated equine influenza vaccine: Efficacy against a representative
      clade 2 equine influenza virus, IFNgamma synthesis and duration of humoral
      immunity.
AB  - Equine influenza (EI) is a serious respiratory disease of horses induced by the
      equine influenza virus (EIV). Surveillance, quarantine procedures and vaccination
      are widely used to prevent or to contain the disease. This study aimed to further
      characterise the immune response induced by a non-updated inactivated EI and
      tetanus vaccine, including protection against a representative EIV isolate of the
      Florida clade 2 sublineage. Seven ponies were vaccinated twice with Duvaxyn IE-T
      Plus at an interval of four weeks. Five ponies remained unvaccinated. All ponies
      were experimentally infected with the EIV strain A/eq/Richmond/1/07 two weeks
      after the second vaccination. Clinical signs of disease were recorded and virus
      shedding was measured after experimental infection. Antibody response and EIV
      specific IFNgamma synthesis, a marker of cell-mediated immunity, were measured at
      different time points of the study. Vaccination resulted in significant
      protection against clinical signs of disease induced by A/eq/Richmond/1/07 and
      reduced virus shedding when challenged at the peak of immunity. Antigenic drift
      has been shown to reduce protection against EIV infection. Inclusion of a more
      recent and representative EIV vaccine strain, as recommended by the OIE expert
      surveillance panel on equine influenza vaccine, may maximise field protection. In
      addition, significant levels of EIV-specific IFNgamma synthesis by peripheral
      blood lymphocytes were detected in immunised ponies, which provided a first
      evidence of CMI stimulation after vaccination with a whole inactivated EIV.
      Duration of humoral response was also retrospectively investigated in 14 horses
      vaccinated under field condition and following the appropriate immunisation
      schedule, up to 599 days after first immunisation. This study revealed that most
      immunised horses maintained significant levels of cross-reactive SRH antibody for
      a prolonged period of time, but individual monitoring may be beneficial to
      identify poor vaccine responders.

PMID- 23146169
TI  - Emergence of fatal European genotype CyHV-3/KHV in mainland China.
AB  - Cyprinid herpesvirus 3 (CyHV-3), also known as koi herpesvirus (KHV), is a highly
      infectious causative agent to common carp and koi worldwide. The virus is mainly
      consisted of European and Asian genotype isolates. To date, no European genotype
      CyHV-3 has been found emerging in the East and Southeast Asian regions. In late
      March 2011, an outbreak of CyHV-3 disease occurred in Guangzhou City, Guangdong
      Province, China, resulting in the deaths of approximately 200 large-sized adult
      koi within four weeks. One moribund koi was sampled for CyHV-3 isolation. Thus, a
      CyHV-3 was isolated in KCF-1 cells and designated as KHV-GZ11. Abundant mature or
      immature virions in infected KCF-1 cells were observed under a transmission
      electron micrograph. In addition, intra-nuclear inclusion body-like structures
      with masses of virions were also observed. Based on the TK and ORF136H genes, the
      sequence analyses revealed that KHV-GZ11 is a distinct European genotype of CyHV
      3. Moreover, the infectivity experiment showed that KHV-GZ11 was highly virulent
      to koi. In summary, we are the first to confirm the emergence of fatal European
      genotype CyHV-3/KHV in East and Southeast Asia. Our study will provide new
      insight to explore the virus origin and epidemiology, as well as its
      pathogenicity.

PMID- 23146170
TI  - Isolation of canine Anaplasma phagocytophilum strains from clinical blood samples
      using the Ixodes ricinus cell line IRE/CTVM20.
AB  - Anaplasma phagocytophilum is an intracellular tick-borne rickettsial pathogen,
      which causes granulocytic anaplasmosis in various species of livestock and
      companion animals and also in humans. Previously A. phagocytophilum has been
      isolated and propagated in cell lines derived from the tick Ixodes scapularis and
      in the human promyelocytic cell line HL60. In this study we used the Ixodes
      ricinus-derived cell line IRE/CTVM20 to isolate and propagate two new canine
      strains of A. phagocytophilum. Blood samples were collected by veterinarians from
      two dogs, one from Germany and the other from Austria. Suspicion of clinical
      canine granulocytic anaplasmosis was raised by the treating veterinarians and
      after confirmation of A. phagocytophilum infection by real-time PCR, buffy coat
      cells were isolated and co-cultivated with IRE/CTVM20 cells maintained at 28 
      degrees C in L15/L15B medium. In the tick cells, rickettsial inclusions were
      first recognised after 86 days of incubation. Electron microscopic examination of
      tick cells infected with one of the isolates revealed cytoplasmic vacuoles
      containing pleomorphic organisms with individual bacteria enveloped by a bilayer
      membrane. Sequencing of 16S rRNA genes confirmed the isolation of A.
      phagocytophilum and showed the highest identity to the A. phagocytophilum human
      HZ strain. The two A. phagocytophilum isolates were passaged several times in
      IRE/CTVM20 cells and transferred to the I. scapularis cell line ISE6. This
      confirms for the first time the successful establishment and continuous
      cultivation of this pathogen in I. ricinus cells as well as infectivity of these
      canine strains for I. scapularis cells.

PMID- 23146171
TI  - Effects of protein interaction data integration, representation and reliability
      on the use of network properties for drug target prediction.
AB  - BACKGROUND: Previous studies have noted that drug targets appear to be associated
      with higher-degree or higher-centrality proteins in interaction networks. These
      studies explicitly or tacitly make choices of different source databases, data
      integration strategies, representation of proteins and complexes, and data
      reliability assumptions. Here we examined how the use of different data
      integration and representation techniques, or different notions of reliability,
      may affect the efficacy of degree and centrality as features in drug target
      prediction. RESULTS: Fifty percent of drug targets have a degree of less than
      nine, and ninety-five percent have a degree of less than ninety. We found that
      drug targets are over-represented in higher degree bins - this relationship is
      only seen for the consolidated interactome and it is not dependent on n-ary
      interaction data or its representation. Degree acts as a weak predictive feature
      for drug-target status and using more reliable subsets of the data does not
      increase this performance. However, performance does increase if only cancer
      related drug targets are considered. We also note that a protein's membership in
      pathway records can act as a predictive feature that is better than degree and
      that high-centrality may be an indicator of a drug that is more likely to be
      withdrawn. CONCLUSIONS: These results show that protein interaction data
      integration and cleaning is an important consideration when incorporating network
      properties as predictive features for drug-target status. The provided scripts
      and data sets offer a starting point for further studies and cross-comparison of
      methods.

PMID- 23146172
TI  - Idiopathic pulmonary fibrosis: diagnostic pitfalls and therapeutic challenges.
AB  - Idiopathic pulmonary fibrosis (IPF), the most common of the idiopathic
      interstitial pneumonias, is a devastating condition that carries a prognosis
      worse than that of many cancers. As such, it represents one of the most
      challenging diseases for chest physicians. The diagnostic process is complex and
      relies on the clinician integrating clinical, laboratory, radiologic, and/or
      pathologic data. Therefore, a close collaboration between chest physicians,
      radiologists, and pathologists experienced in the diagnosis of interstitial lung
      diseases (ILDs) is necessary in order to minimize diagnostic uncertainty.
      Similarly, the management of IPF continues to pose major difficulties. However,
      while there are no proven effective therapies for IPF beyond lung
      transplantation, recent trials of novel agents suggest that pharmacological
      treatment may retard the progression of the disease. In this regard, enrolment of
      patients into clinical trials is considered the "best current practice"by the
      most recent guidelines as it offers IPF patients the chance to receive new agents
      that may be more effective than current therapies. A more recent trend focusing
      on improving quality of life in IPF patients has also been gaining ground.The
      diagnosis and management of IPF remains a constant challenge for even the most
      experienced of clinicians. However, a multidisciplinary approach to this complex
      disease is steadily improving diagnostic accuracy, while recent advances in the
      pharmacological therapy offer the genuine promise of future treatments for this
      devastating disease.

PMID- 23146174
TI  - Capture myopathy in live-stranded cetaceans.
AB  - A group of 51 cetaceans that had been stranded alive on the coasts of the Canary
      Islands, experienced human capture/rescue interactions and then died, were
      necropsied over a 12-year period. Of these cetaceans, 25 had haemodynamic lesions
      indicative of multiorganic vascular shock, degenerative muscle lesions affecting
      both skeletal and cardiac muscles and myoglobinuric nephrosis typical of capture
      myopathy (CM). Because macroscopic lesions in muscles and kidneys were not always
      obvious, a standard protocol was developed where the longissimus dorsi muscle was
      examined histologically for segmental hypercontraction, contraction band necrosis
      and segmental muscular degeneration and cardiomyocytes studied for
      hypereosinophilic wavy fibres, sarcolemmal and perinuclear vacuolation and
      contraction band necrosis. Light microscopic skeletal and cardiac muscle lesions
      in all CM animals were confirmed as ante mortem by immunohistochemical assay for
      myoglobin loss from and fibrinogen entry into affected myofibres. All animals had
      tubular nephrosis with casts and tubular myoglobin. The oxidative stress-related
      marker HSP70 was demonstrated immunohistochemically in tubular epithelium.
      Although the syndrome related to death of live-stranded cetaceans is
      multifactorial, this study documents that a clinicopathological syndrome
      comparable to CM of terrestrial wildlife has a role in stranding outcomes.

PMID- 23146173
TI  - Prevalence of attenuated psychotic symptoms and their relationship with DSM-IV
      diagnoses in a general psychiatric outpatient clinic.
AB  - OBJECTIVE: Attenuated psychosis syndrome (APS) is being proposed for inclusion in
      Section III of DSM-5 for those impaired by subthreshold psychotic symptoms that
      are not better accounted for by another diagnosis and not meeting criteria for a
      psychotic disorder. The rationale is to identify patients who are at high risk
      for transition to a psychotic disorder in the near future. However, the potential
      impact of using this new diagnosis in routine clinical practice settings has not
      been carefully examined. METHOD: As part of the Rhode Island Methods to Improve
      Diagnostic Assessment and Services (MIDAS) project, a treatment-seeking
      psychiatric outpatient sample (n = 1,257) recruited from June 1997 to June 2002
      completed a self-report measure of psychiatric symptoms and afterward were
      administered structured clinical interviews. For the current post hoc study, we
      investigated the prevalence rate of endorsing attenuated psychotic experiences to
      identify patients who could potentially meet criteria for APS. RESULTS: After the
      exclusion of those with lifetime DSM-IV psychotic disorders, psychotic
      experiences remained highly prevalent in the sample (28% reported at least 1
      psychotic experience during the past 2 weeks), and rates were similar across all
      major DSM-IV diagnostic categories. Only 1 patient (0.08%) reported psychotic
      experiences but did not meet criteria for another current DSM disorder; however,
      this individual endorsed other nonpsychotic symptoms of greater severity.
      Psychotic experience endorsement was positively correlated with nearly all other
      nonpsychotic symptom domains, and multivariate analysis showed that general
      clinical severity predicted endorsement of psychotic experiences (P values <
      .001). CONCLUSIONS: We could not identify any patients who clearly met criteria
      for APS alone in our sample. Psychotic experiences appear to be common in
      outpatients and represent nonspecific indicators of psychopathology. Diagnosing
      APS in the community could result in high rates of false-positives or high rates
      of APS "comorbidity" with other nonpsychotic disorders, leading to the increased
      use of antipsychotic medications without clear need. Therefore, the clinical
      utility of adding APS to the diagnostic system remains highly questionable.

PMID- 23146175
TI  - Flexibility within the middle ears of vertebrates.
AB  - INTRODUCTION AND AIMS: Tympanic middle ears have evolved multiple times
      independently among vertebrates, and share common features. We review flexibility
      within tympanic middle ears and consider its physiological and clinical
      implications. COMPARATIVE ANATOMY: The chain of conducting elements is flexible:
      even the 'single ossicle' ears of most non-mammalian tetrapods are functionally
      'double ossicle' ears due to mobile articulations between the stapes and
      extrastapes; there may also be bending within individual elements. SIMPLE MODELS:
      Simple models suggest that flexibility will generally reduce the transmission of
      sound energy through the middle ear, although in certain theoretical situations
      flexibility within or between conducting elements might improve transmission. The
      most obvious role of middle-ear flexibility is to protect the inner ear from high
      amplitude displacements. CLINICAL IMPLICATIONS: Inter-ossicular joint dysfunction
      is associated with a number of pathologies in humans. We examine attempts to
      improve prosthesis design by incorporating flexible components.

PMID- 23146176
TI  - Acoustic propagation in viscous fluid with uniform flow and a novel design
      methodology for ultrasonic flow meter.
AB  - Ultrasonic flow meter with non-invasive no-moving-parts construction has good
      prospective application for space on-orbit fluid gauging. In traditional pulse
      transit time flow meter, inconsistency of ultrasonic transducers leads to
      measurement error and plane wave theory, bases of transit time flow meter, is
      valuable only for low-frequency wave propagation in inviscid fluid and will lose
      feasibility when fluid viscosity is considered. In this paper, based on the
      hydrodynamics of viscous fluid, wave propagation with uniform flow profile is
      mathematically formulated and a novel solution for viscous fluid using potential
      theory is firstly presented. Then a novel design methodology of continuous
      ultrasonic flow meter is proposed, where high measurement rangeability and
      accuracy are guaranteed individually by solving the integral ambiguity using
      multi-tone wide laning strategy and the fractional phase shift using phase lock
      loop tracking method. A comparison with transit time ultrasonic flow meter shows
      the advantage of proposed methodology. In the end, parametric analysis of
      viscosity on wave propagation and ultrasonic flow meter is compressively
      investigated.

PMID- 23146177
TI  - Ultrasonic measurement of bulk and shear moduli variations in porous alumina
      media.
AB  - In this paper we studied some acoustical parameters of a porous medium based on
      the Biot's theory. The basic idea was to find, using an inversion method,
      variations in the bulk modulus K(b) and the shear modulus G(b) in the frequency
      domain. This was achieved by comparing the theoretical and experimental results
      obtained on a selection of porous alumina samples with different physical
      characteristics. Then, using the transmission coefficient, a numerical process
      was applied to a virtual porous alumina medium in order to find K(b) and G(b)
      values at low frequency under static conditions. Using a frequency range of 50kHz
      to 600kHz, fast and slow waves were considered and both were included in the
      transmission coefficient.

PMID- 23146179
TI  - Atypical presentation of myoepithelial hamartoma in the antrum of the stomach,
      mimicking a gastrointestinal stromal tumor: a case report.
AB  - INTRODUCTION: A myoepithelial hamartoma is a very uncommon submucosal tumor of
      the stomach. In an atypical presentation in our case, it mimicked the clinical
      presentation of a gastrointestinal stromal tumor. To the best of our knowledge,
      it is the first case of a hamartoma of the stomach reported from Bangladesh and
      one of few cases described in the literature. CASE PRESENTATION: We describe the
      case of a 35-year-old Bengali man with recurrent epigastric pain and occasional
      vomiting with radiographic findings of a gut mass. An upper gastrointestinal
      endoscopy revealed a healed duodenal ulcer, deformed 'D' bulb and a submucosal
      swelling in his antrum. Ultrasonography and a contrast-enhanced computed
      tomography scan confirmed the presence of a well-defined, oval gut mass in his
      upper abdomen, compressing his duodenum. The mass had a mixed density and was
      considered to probably be a gastrointestinal stromal tumor. Ultrasonography
      guided fine needle aspiration cytology was inconclusive. After resection at
      laparotomy, a histopathological examination revealed a myoepithelial hamartoma.
      These tumors are characterized by hypertrophic smooth muscle bands surrounding
      varied epithelial elements, which may be arranged in diverse patterns such as
      simple glandular structure, Brunner's gland, pancreatic ducts and sometimes
      pancreatic acini. This case report is complemented by a literature review
      relating to the atypical presentation. CONCLUSION: Gut masses need to be
      investigated thoroughly and the possibility of rare tumors should not be
      excluded. Although the recommended treatment for such lesions is limited
      resection, radical procedures such as a pancreaticoduodenectomy are often
      performed when the lesion occurs in the periampullary area because of
      preoperative misdiagnosis as a carcinoma. Therefore, it is essential for
      clinicians to maintain current knowledge of the lesion to avoid inaccurate
      diagnosis and prevent unnecessary surgery.

PMID- 23146178
TI  - The Polycomb group protein MEDEA and the DNA methyltransferase MET1 interact to
      repress autonomous endosperm development in Arabidopsis.
AB  - In flowering plants, double fertilization of the female gametes, the egg and the
      central cell, initiates seed development to give rise to a diploid embryo and the
      triploid endosperm. In the absence of fertilization, the FERTILIZATION
      INDEPENDENT SEED Polycomb Repressive Complex 2 (FIS-PRC2) represses this
      developmental process by histone methylation of certain target genes. The
      FERTILIZATION-INDEPENDENT SEED (FIS) class genes MEDEA (MEA) and FERTILIZATION
      INDEPENDENT ENDOSPERM (FIE) encode two of the core components of this complex. In
      addition, DNA methylation establishes and maintains the repression of gene
      activity, for instance via DNA METHYLTRANSFERASE1 (MET1), which maintains
      methylation of symmetric CpG residues. Here, we demonstrate that Arabidopsis MET1
      interacts with MEA in vitro and in a yeast two-hybrid assay, similar to the
      previously identified interaction of the mammalian homologues DNMT1 and EZH2.
      MET1 and MEA share overlapping expression patterns in reproductive tissues before
      and after fertilization, a prerequisite for an interaction in vivo. Importantly,
      a much higher percentage of central cells initiate endosperm development in the
      absence of fertilization in mea-1/MEA; met1-3/MET1 as compared to mea-1/MEA
      mutant plants. In addition, DNA methylation at the PHERES1 and MEA loci,
      imprinted target genes of the FIS-PRC2, was affected in the mea-1 mutant compared
      with wild-type embryos. In conclusion, our data suggest a mechanistic link
      between two major epigenetic pathways involved in histone and DNA methylation in
      plants by physical interaction of MET1 with the FIS-PRC2 core component MEA. This
      concerted action is relevant for the repression of seed development in the
      absence of fertilization.

PMID- 23146180
TI  - Nucleic acid fluorescent probes for biological sensing.
AB  - Nucleic acid fluorescent probes are playing increasingly important roles in
      biological sensing in recent years. In addition to the conventional functions of
      single-stranded DNA/RNA to hybridize with their complementary strands, affinity
      nucleic acids (aptamers) with specific target  binding properties have also been
      developed, which has greatly broadened the application of nucleic acid
      fluorescent probes to the detection of a large variety of analytes, including
      small molecules, proteins, ions, and even whole cells. Another chemical property
      of nucleic acids is to act  as substrates for various nucleic acid enzymes. This
      property can be utilized not only to detect those enzymes and screen their
      inhibitors, but also employed to develop effective signal amplification systems,
      which implies extensive applications. This review mainly covers the biosensing
      methods  based on the above three types of nucleic acid fluorescent probes. The
      most widely used intensity-based biosensing assays are covered first, including
      nucleic acid probe-based signal amplification methods. Then fluorescence
      lifetime, fluorescence anisotropy, and fluorescence correlation spectroscopy 
      assays are introduced, respectively. As a rapidly developing field, fluorescence
      imaging approaches are also briefly summarized.

PMID- 23146181
TI  - Deep-ultraviolet (UV) resonance raman spectroscopy as a tool for quality control
      of formulated therapeutic proteins.
AB  - A deep-ultraviolet (UV) Raman spectrometer with excitation source tunable from
      193 to 210 nm has been built and characterized. The dispersion of the
      spectrometer over the entire range was measured and described theoretically. The
      relative sensitivity of the spectrometer was estimated using the integrated
      intensity ratio of two Raman bands of cyclohexane. Resonance Raman spectra of
      three formulated insulin products were measured and compared. A band-targeted
      entropy minimization algorithm was applied to the collected spectra for mixture
      analysis of insulin products. We conclude that it is feasible to develop robust
      qualitative methods for quality control of protein-based formulated drug using
      DUVRR spectroscopy.

PMID- 23146182
TI  - Multivariate analysis of micro-Raman spectra of thermoplastic polyurethane blends
      using principal component analysis and principal component regression.
AB  - Probing the specific hydrogen-bonding behavior of thermoplastic polyurethane
      (TPU) blends using vibrational spectroscopies remains the sin qua non for
      understanding the link between hydrogen-bonding and phase-segregation behavior.
      However, current literature holds to more traditional  univariate approaches when
      studying the morphologically interesting normal molecular vibrations of TPUs. In
      the present study, multivariate analysis, including principal component analysis
      (PCA) and principal component regression (PCR), is used to scrutinize the
      relevant Raman bands acquired  from a binary mixture of analogous TPU copolymer
      blends. Considering the near identical behavior of selected spectral regions, PCA
      was capable of isolating linear and nonlinear composition-dependent trends on PC
      scores plots. From here, the PC scores, extracted from wavelengths comprising 
      the carbonyl stretching region (1681-1764 cm(-1)), CH(2) deformations (1380-1500
      cm(-1)), aromatic stretch from the hard segment (1617 cm(-1)), and amide II mixed
      band (1540 cm(-1)), were used to explicitly  predict the mole fraction of hard
      segment present in each blend using PCR. Spectral preprocessing, wavelength
      selection, and variable scaling were major factors in PCR accurately predicting
      the weight fraction of each copolymer in spite of the clearly evident, blend
      specific spectroscopic  behavior.

PMID- 23146183
TI  - Single-pulse standoff Raman detection of chemicals from 120 m distance during
      daytime.
AB  - The capability to analyze and detect the composition of distant samples
      (minerals, organics, and chemicals) in real time is of interest for various
      fields including detecting explosives, geological surveying, and pollution
      mapping. For the past 10 years, the University of Hawaii has been developing
      standoff Raman systems suitable for measuring Raman spectra of various chemicals
      in daytime or nighttime. In this article we present standoff Raman spectra of
      various minerals and chemicals obtained from a distance of 120 m using single
      laser pulse excitation during daytime. The standoff Raman system utilizes an 8
      inch Meade telescope as collection optics and a frequency-doubled 532 nm Nd : YAG
      laser with pulse energy of 100 mJ/pulse and pulse width of 10 ns. A gated
      intensified charge-coupled device (ICCD) detector is used to measure time
      resolved Raman spectra in daytime with detection time of 100 ns. A gate delay of
      800 ns (equivalent to target placed at 120 m distance) was used to minimize
      interference from the atmospheric gases along the laser beam path and near-field
      scattering. Reproducible, good quality single-shot Raman spectra of various
      inorganic and organic chemicals and minerals such as ammonium nitrate, potassium
      perchlorate, sulfur, gypsum, calcite, benzene, nitrobenzene, etc., were obtained
      through sealed glass vials during daytime. The data indicate that various
      chemicals could easily be identified from their Raman fingerprint spectra from a
      far standoff distance in real time using single-shot laser excitation.

PMID- 23146184
TI  - Evaluation of laser-induced breakdown spectroscopy (LIBS) for measurement of
      silica on filter samples of coal dust.
AB  - Airborne silica dust (quartz) is common in coal mines and represents a
      respiratory hazard that can lead to silicosis, a potentially fatal lung disease.
      With an eye toward developing a portable monitoring device for rapid analysis of
      silica dust, laser-induced breakdown spectroscopy (LIBS) was used to quantify
      quartz in coal dust samples collected on filter media. Pure silica (Min-U-SilTM
      5), Georgia kaolin, and Pittsburgh-4 and Illinois-6 coal dusts were deposited
      separately and at multiple mass loadings onto 37-mm polyvinylchloride (PVC)
      filters. LIBS-generated silicon emission was monitored at 288.16 nm, and non
      silica contributions to that signal from kaolinite were removed by simultaneously
      detecting aluminum. Measurements of the four samples were used to calculate
      limits of detection (LOD) for silicon and aluminum of approximately 0.08
      MUg/cm(2) and 0.05 MUg/cm(2), respectively (corresponding to 0.16 MUg/cm(2) and
      0.20 MUg/cm(2) for silica and kaolinite, respectively). Relative errors of
      prediction are around 10%. Results demonstrate that LIBS can dependably quantify
      silica on filter samples of coal dust and confirm that accurate quantification
      can be achieved for very lightly loaded samples, which supports the potential
      application of LIBS for rapid, in-field monitoring.

PMID- 23146185
TI  - Fast and environmentally friendly quantitative analysis of active agents in anti
      diabetic tablets by an alternative laser-induced breakdown spectroscopy (LIBS)
      method and comparison to a validated reversed-phase high-performance liquid
      chromatography (RP-HPLC) method.
AB  - Laser-induced breakdown spectroscopy (LIBS) is evaluated as a potential analytic
      technique for rapid screening and quality control of anti-diabetic tablets. This
      paper proposes a simple LIBS-based method for the quantitative analysis of two
      active pharmaceutical ingredients (APIs): metformin (Met) and glybenclamide
      (Gly). In order to quantify both APIs, chlorine (Cl) concentration was estimated
      by employing the Cl/Br optical emission ratio, where Br was introduced as
      internal standard. Calibration curves were prepared, achieving linearity higher
      than 99%. On the other hand, for comparison to the proposed method, an isocratic
      reversed-phase high-performance liquid chromatography (RP-HPLC) method was also
      developed for quantitative determination of the same analytes by ultraviolet (UV)
      detection. The chromatographic separation was achieved on a Phenomenex Hypersil
      C18, 250 mm * 4.6 mm, 5 MUm column. The mobile phase was K(2)HPO(4)/H(3)PO(4)
      CH(3)OH and flow rate was 1.0 mL min(-1). The method is linear over a range of 10
      60 MUg mL(-1) for Gly and 5-30 MUg mL(-1) for Met and the correlation
      coefficients were >=0.99. Recoveries were found to be in the range of 95-101%.
      Furthermore, four different commercial brands of each active agent were evaluated
      by both proposed LIBS and chromatographic methods and results were compared with
      each other. The comparison was satisfactorily validated by analysis of variance
      (ANOVA).

PMID- 23146186
TI  - Chemometric method of spectra analysis leading to isolation of lysozyme and CtDNA
      spectra affected by osmolytes.
AB  - In this paper we present a chemometric method of analysis leading to isolation of
      Fourier transform infrared (FT-IR) spectra of biomacromolecules (HEW lysozyme,
      ctDNA) affected by osmolytes (trimethylamine-N-oxide and N,N,N-trimethylglycine,
      respectively) in aqueous solutions. The method is based on the difference spectra
      method primarily used to characterize the structure of solvent affected by
      solute. The cyclical usage of factor analysis allows precise information to be
      obtained on the shape of "affected spectra" of analyzed biomacromolecules.
      "Affected spectra" of selected biomacromolecules give valuable information on
      their structure in the presence of the osmolytes in solution, as well as on the
      level of perturbation in dependence of osmolyte concentration. The method also
      gives a possibility of insight into the mechanism of interaction in presented
      types of systems. It can be easily adapted to various chemical and biochemical
      problems where vibrational or ultraviolet-visible (UV-Vis) spectroscopy is used.

PMID- 23146187
TI  - Rapid, nondestructive estimation of surface polymer layer thickness using
      attenuated total reflection fourier transform infrared (ATR FT-IR) spectroscopy
      and synthetic spectra derived from optical principles.
AB  - We have developed a rapid, nondestructive analytical method that estimates the
      thickness of a surface polymer layer with high precision but unknown accuracy
      using a single attenuated total reflection Fourier transform infrared (ATR FT-IR)
      measurement. Because the method is rapid, nondestructive, and requires no sample
      preparation, it is ideal as a process analytical technique. Prior to
      implementation, the ATR FT-IR spectrum of the substrate layer pure component and
      the ATR FT-IR and real refractive index spectra of the surface layer pure
      component must be known. From these three input spectra a synthetic mid-infrared
      spectral matrix of surface layers 0 nm to 10,000 nm thick on substrate is created
      de novo. A minimum statistical distance match between a process sample's ATR FT
      IR spectrum and the synthetic spectral matrix provides the thickness of that
      sample. We show that this method can be used to successfully estimate the
      thickness of polysulfobetaine surface modification, a hydrated polymeric surface
      layer covalently bonded onto a polyetherurethane substrate. A database of 1850
      sample spectra was examined. Spectrochemical matrix-effect unknowns, such as the
      nonuniform and molecularly novel polysulfobetaine-polyetherurethane interface,
      were found to be minimal. A partial least squares regression analysis of the
      database spectra versus their thicknesses as calculated by the method described
      yielded an estimate of precision of +/-52 nm.

PMID- 23146188
TI  - Structure of alkyne monolayers on hydrogen-terminated Si(100) surfaces
      investigated by external reflection infrared spectroscopy.
AB  - Monolayers of terminal alkynes with long hydrocarbon chains C(n)H(2n+1)C=CH (n =
      10, 13, 16) were prepared on Si(100) substrates via thermally induced
      hydrosilylation and the surface orientation of the hydrocarbon chains was
      investigated by external reflection infrared spectroscopy. It was found that
      under rigorous exclusion of oxygen in the monolayer preparation process, all
      three compounds yield highly characteristic IR reflection spectra, consisting of
      upward-pointing nu(CH(2)) absorptions and downward-pointing nu(CH(3))
      absorptions, indicative of a highly ordered anisotropic film structure. Via
      spectral simulations it was found that the methylene backbones (CH(2))(n) in
      these films adopt a uniform, all-trans conformation with a tilt angle of about 30
      degrees  toward the surface normal, whereas the chain termini are disordered and
      give an isotropic film surface composed of randomly oriented CH(3) groups. Lower
      quality films, which are hardly distinguishable from highly ordered films by
      other methods, but have been shown to exhibit inferior electrical properties, are
      clearly identified in their infrared (IR) spectra as partly disordered
      structures. External reflection IR therefore proves to be an exceptionally
      sensitive tool to detect structural defects in these monolayers.

PMID- 23146189
TI  - Automated cosmic spike filter optimized for process Raman spectroscopy.
AB  - Despite the existence of various methods to remove cosmic spikes from Raman data,
      only a few of them are suitable for process Raman spectroscopy. The disadvantages
      of these algorithms include increased analysis time, low accuracy of spike
      detection, or reliance on variable parameters  that must be chosen by trial and
      error in each case. We demonstrate a novel approach to detecting cosmic spikes in
      process Raman data and validate it using a wide range of experimental data. This
      new method features a multistage spike recognition algorithm that is based on
      tracking sharp changes  of intensity in the time domain. The algorithm
      effectively distinguishes cosmic spikes from random spectral noise and abrupt
      variations of Raman peaks, allowing accurate detection of both high and low
      intensity cosmic spikes. The procedure is free from variable user-defined
      parameters and  operates reliably in a fully automated manner with a wide range
      of time-series process Raman data sets containing more than 40 to 50 spectra.

PMID- 23146190
TI  - Semi-blind spectral deconvolution with adaptive Tikhonov regularization.
AB  - Deconvolution has become one of the most used methods for improving spectral
      resolution. Deconvolution is an ill-posed problem, especially when the point
      spread function (PSF) is unknown. Non-blind deconvolution methods use a
      predefined PSF, but in practice the PSF is not known exactly. Blind deconvolution
      methods estimate the PSF and spectrum simultaneously from the observed spectra,
      which become even more difficult in the presence of strong noise. In this paper,
      we present a semi-blind deconvolution method to improve the spectral resolution
      that does not assume a known PSF but models it as a parametric function in
      combination with the a priori knowledge about the characteristics of the
      instrumental response. First, we construct the energy functional, including
      Tikhonov regularization terms for both the spectrum and the parametric PSF.
      Moreover, an adaptive weighting term is devised in terms of the magnitude of the
      first derivative of spectral data to adjust the Tikhonov regularization for the
      spectrum. Then we minimize the energy functional to obtain the spectrum and the
      parameters of the PSF. We also discuss how to select the regularization
      parameters. Comparative results with other deconvolution methods on simulated
      degraded spectra, as well as on experimental infrared spectra, are presented.

PMID- 23146191
TI  - Composition analysis of scattering liquids based on spatially offset visible-near
      infrared spectroscopy.
AB  - Spatially offset visible-near-infrared (VIS-NIR) spectroscopy was used to analyze
      of chemical compositions of the scattering liquids in the visible and near
      infrared region from 530 to 930 nm. An experimental setup was designed based on a
      supercontinuum white-light laser source, an electrically controlled translation
      stage, and a high-performance spectrometer. The spatially offset spectra of the
      scattering liquids (composed of diluted Intralipid((r)) 20% in distilled water)
      were measured at 24 sequential positions in the radial distribution from the
      incident light. A partial least squares regression method was applied to obtain
      the Intralipid((r)) concentration from the spatially offset spectra. The results
      showed that the prediction accuracy of the Intralipid((r)) concentration obtained
      from the spectra collected at multiple sample points was better than that
      obtained from the spectra collected at a single sample point. The coefficient of
      determination in the prediction set is 0.9835 at the optimized number of sample
      points.

PMID- 23146192
TI  - Analysis and classification of heterogeneous kidney stones using laser-induced
      breakdown spectroscopy (LIBS).
AB  - Kidney stones were analyzed using laser-induced breakdown spectroscopy (LIBS),
      utilizing a high resolution multi-channel charge-coupled device (CCD)
      spectrometer and a nanosecond-pulse Nd : YAG laser. The kidney stones were also
      characterized using X-ray diffraction (XRD)  and X-ray fluorescence (XRF)
      techniques for comparative analysis. It was found that the ratio of hydrogen (H)
      to carbon (C) was an important indicator of organic compounds such as uric acid.
      Advantages of LIBS, especially with regards to amount of sample required and
      sample preparation as  well as the ability to carry out elemental analysis and
      classification of kidney stones simultaneously, over other analytical techniques
      such as XRD and XRF are discussed. The common minor elements detected in the
      kidney stones include P, S, Si, Ti, and Zn. Principal component analysis (PCA) 
      and partial least squares discriminant analysis (PLS-DA) of broadband LIBS
      spectra were employed for classifying different types of kidney stones. The
      results are beneficial in understanding kidney stone formation processes, which
      can lead to preventive therapeutic strategies and treatment  methods for
      urological patients.

PMID- 23146193
TI  - Wavelength anomalies in ultraviolet-visible spectrophotometry.
AB  - Spectral scans of atomic line emission sources with a Shimadzu UV2101PC
      spectrophotometer show that the nominal wavelength depends upon the instrumental
      slit width, the wavelength sampling interval, and for some slit widths, also on
      the specified spectral range. The range dependence is manifested as a smoothing
      that occurs when the range includes >65 sampled wavelengths, and it affects both
      the wavelength and the line shape. For spectra not subject to this smoothing, the
      wavelength error looks like a one-sample misassociation of the wavelength and
      photometric readings. However, the instrument does reliably move to a specified
      wavelength, independent of the scan parameter settings. These behaviors do not
      seem to be documented anywhere but have been present in the software for
      operating this instrument for about two decades.

PMID- 23146194
TI  - Morphological characteristics of the young scoliotic dancer.
AB  - BACKGROUND: The literature lacks important data about the relationship between
      scoliosis and growth process, scoliosis and intensive exercise, scoliosis and
      morphological characteristics, and scoliosis and injuries, among young dancers.
      OBJECTIVE: The aims of the present study were to determine the extent to which
      dance experience, body structure, anatomical anomalies and injuries are
      associated with scoliosis, and to identify variables able to discriminate between
      scoliotic and non-scoliotic female dancers at time of screening. DESIGN: Cross
      sectional cohort study. METHODS: One thousand two hundred and eighty-eight non
      professional female dancers, aged 8-16 years, were screened for the current
      study. We determined their morphometrical profile (height, weight, BMI), dance
      discipline (as hours of practice per week), manifestation of anatomical
      anomalies, and existing injuries. All dancers were clinically examined for
      presence of scoliosis. RESULTS: Three hundred and seven of the 1288 dancers
      (23.8%) were diagnosed as having scoliosis. Dance experience and body structure
      were similar for dancers with or without scoliosis. Scoliotic dancers presented a
      significantly higher prevalence of anatomical anomalies (such as genu varum, and
      hallux valgus). Back injuries were more common among scoliotic dancers compared
      to non-scoliotic dancers. CONCLUSION: Screening and identifying the young
      scoliotic dancers prior to their advancing to higher levels of exercise is
      recommended. The scoliotic dancers should realize that there might be a
      connection between the presence of scoliosis and increased incidence of
      anatomical anomalies and back pain, hence, it should be suggested they seek help
      with an adequate assessment and exercise rehabilitation program.

PMID- 23146196
TI  - The test-retest reliability of gait-related dual task performance in community
      dwelling fallers and non-fallers.
AB  - Gait-related dual task tests have been used to assess differences between fallers
      and non-fallers, without a thorough assessment of reliability. This study
      investigated the test-retest reliability of eight gait-related dual and one
      triple task tests in forty-four community-dwelling older adults (twenty with and
      twenty-four without a history of falls). The reliability of single, dual and
      change in performance (percentage change) from single to dual task conditions was
      assessed. The results showed that single and dual task walking time had fair to
      excellent reliability (ICC=0.53-0.92) across tasks. The percentage change in
      walking time (dual-task decrement) showed only poor to good reliability (ICC=
      0.11 to 0.75). Cognitive task performance speed and accuracy showed poor to good
      reliability in single and dual task conditions (ICC=-0.16 to 0.83). The
      difference between the two conditions in speed and accuracy showed poor to fair
      reliability (ICC=-0.40 to 0.51). A secondary motor task (carrying a cup of water)
      ranged from slightly to moderately reliable in dual task conditions and when
      change in performance was measured (kappa=0.18-0.57). This study showed that
      simple dual task tests are reliable in the single and dual conditions but
      measures of change in performance, which are recommended for dual task
      assessment, are less reliable and is something which needs to be considered in
      future research. Of the nine examined, only one test, the walking while talking
      test, showed good reliability on primary and secondary tasks.

PMID- 23146197
TI  - Continuation transcranial direct current stimulation for the prevention of
      relapse in major depression.
AB  - BACKGROUND: Transcranial direct current stimulation (tDCS) is gaining attention
      as an effective new treatment for major depression. Little is known, however, of
      the duration of antidepressant effects following acute treatment. In this study,
      we describe the use of continuation tDCS treatment for up to 6 months following
      clinical response to an acute treatment course. METHODS: Twenty-six participants
      pooled from two different studies involving different tDCS protocols received
      continuation tDCS treatment on a weekly basis for 3 months and then once per
      fortnight for the final 3 months. Mood ratings were completed at 3 and 6 months.
      Analyses examined clinical predictors of relapse during continuation tDCS
      treatment. RESULTS: The cumulative probability of surviving without relapse was
      83.7% at 3 months and 51.1% at 6 months. Medication resistance was found to be a
      predictor of relapse during continuation tDCS. LIMITATIONS: This was an open
      label prospective study with no control group. Two different forms of tDCS were
      used. CONCLUSION: Similar to other antidepressant treatments, continuation tDCS
      appears to be a useful strategy to prevent relapse following clinical response.
      These preliminary data suggest that the majority of patients maintained
      antidepressant benefit with a continuation schedule of at least weekly treatment.
      Future controlled studies are required to confirm these findings.

PMID- 23146195
TI  - The immunoreceptor tyrosine-based activation motif (ITAM) -related factors are
      increased in synovial tissue and vasculature of rheumatoid arthritic joints.
AB  - INTRODUCTION: The immunoreceptor tyrosine-based activation motif (ITAM) pathway
      provides osteoclast co-stimulatory signals and regulates proliferation, survival
      and differentiation of effector immune cells. In the osteoclast, the receptors
      Triggering Receptor Expressed on Myeloid cells 2 (TREM2) and Osteoclast
      Associated Receptor (OSCAR) and their respective adaptor proteins, DAP12 and
      FcRgamma mediate ITAM signals and induce calcium signaling and the crucial
      transcription factor, NFATc1. In rheumatoid arthritis (RA), OSCAR expression by
      monocytes is inversely correlated with disease activity. Additionally, serum
      levels of OSCAR are reduced in RA patients versus healthy controls suggesting
      that expression and secretion or cleavage of soluble (s) OSCAR is immune
      modulated. Recent data suggest that endothelial cells may also be a source of
      OSCAR. METHODS: ITAM receptors, their adaptor proteins, and NFATc1 and cathepsin
      K were detected in human synovial tissues by immunohistochemistry. Synovial
      tissues from patients with active RA were compared with tissue from patients in
      remission, osteoarthritis (OA) patients and healthy individuals. OSCAR was
      measured by immunoassay in synovial fluids recovered from active RA and OA
      patients. Endothelial cells were cultured with or without 5 ng/mL TNF-alpha or IL
      1beta over 72 hours. Temporal expression of OSCAR mRNA was assessed by qRT PCR
      and OSCAR protein in the supernatant was measured by ELISA. RESULTS:
      Significantly higher (P < 0.05) NFATc1-positive inflammatory cell aggregates were
      found in active RA tissues than in healthy synovial tissue. Similarly, the
      percentage of OSCAR, FcRgamma, DAP12 and TREM2 positive cells was significantly
      higher in active RA tissues compared to the healthy synovial tissue. Notably,
      OSCAR was strongly expressed in the microvasculature of the active RA tissues
      (9/9), inactive RA (8/9) weakly in OA (4/9) but only in the lumen of healthy
      synovial tissue (0/8). OSCAR levels were detected in synovial fluids from both RA
      (47 to 152 ng/mL) and OA (112 to 145 ng/mL) patients. Moreover, OSCAR mRNA
      expression and soluble OSCAR release was stimulated by TNF-alpha and IL1-beta in
      cultured endothelial cells. CONCLUSIONS: Increased levels of ITAM related factors
      were present in synovial tissue from active RA joints compared to OA and healthy
      joints. OSCAR was strongly expressed by the vasculature of active RA patients and
      membrane bound and soluble OSCAR was stimulated by inflammatory mediators in
      endothelial cells in vitro.

PMID- 23146198
TI  - NOS1AP is associated with increased severity of PTSD and depression in untreated
      combat veterans.
AB  - BACKGROUND: Posttraumatic stress disorder (PTSD) and depressive disorder are over
      represented in combat veterans. Veterans with both disorders have an increased
      risk of suicide. The nitric oxide synthase 1 adaptor protein (NOS1AP) gene, which
      modulates stress-evoked N-methyl-d-aspartate (NMDA) activity, was investigated in
      combat veterans. METHODS: A comprehensive genetic analysis of NOS1AP and its
      association with PTSD was investigated in Vietnam combat veterans with PTSD
      (n=121) and a group of healthy control individuals (n=237). PTSD patients were
      assessed for symptom severity and level of depression using the Mississippi Scale
      for Combat-Related PTSD and the Beck Depression Inventory-II (BDI). RESULTS: The
      G allele of NOS1AP SNP rs386231 was significantly associated with PTSD (p=0.002).
      Analysis of variance revealed significant differences in BDI-II and Mississippi
      scores between genotypes for rs386231 with the GG genotype associated with
      increased severity of depression (p=0.002 F=6.839) and higher Mississippi Scale
      for Combat-Related PTSD scores (p=0.033). Haplotype analysis revealed that the
      C/G haplotype (rs451275/rs386231) was significantly associated with PTSD
      (p=0.001). LIMITATIONS: The sample sizes in our study were not sufficient to
      detect SNP associations with very small effects. In addition the study was
      limited by its cross sectional design. CONCLUSIONS: This is the first study
      reporting that a variant of the NOS1AP gene is associated with PTSD. Our data
      also suggest that a genetic variant in NOS1AP may increase the susceptibility to
      severe depression in patients with PTSD and increased risk for suicide.

PMID- 23146201
TI  - Embryo transfer in domestic South American camelids.
AB  - Intraspecific and interspecific embryo transfer in domestic South American
      camelids is developing into a well-established technique. Reports reveal many
      benefits of using reproductive biotechnologies to allow rapid propagation of
      alpacas and llamas of high genetic merit (e.g., high fiber quality, preserve
      color variation). The objective of this review is to provide up-to-date
      information about embryo transfer in domestic South American camelids. Specific
      information is provided on criteria for male selection, donor and recipient
      synchronization, the practice of single- vs. super-ovulation protocols, embryo
      recovery and transfer techniques, advances in cryopreservation of embryos,
      results of intra- and inter-specific transfer, and the future of the embryo
      transfer in domestic South American camelids.

PMID- 23146200
TI  - Use of assisted reproduction for the improvement of milk production in dairy
      camels (Camelus dromedarius).
AB  - Despite their production potential and ability to survive on marginal resources
      in extreme conditions, dromedaries have not been exploited as an important food
      source. Camels have not been specifically selected for milk production, and
      genetic improvement has been negligible. High individual variation in milk
      production both within the population and within breeds provides a good base for
      selection and genetic progress. In this paper, we discuss the possibilities and
      constraints of selective breeding for milk production in camels, and include a
      summary of the use of embryo transfer at the world's first camel dairy farm.
      Embryo transfer is an integral part of the breeding strategy at the camel dairy
      farm because it increases selection intensity and decreases the generation
      interval. Using high milk-producing camels as donors and low producing camels as
      recipients, 146 embryos were recovered (6.1+/-1.0embryos/donor; range: 0-18).
      Embryos were transferred non-surgically into 111 recipients (83 single and 28
      twin embryo transfers). Pregnancy rate at 21 days and 5 months was 55% (61/111)
      and 45% (50/111), respectively. Finally, a total of 46 recipients delivered a
      live calf. These results document the utility of embryo transfer using high milk
      producing dromedaries as donors.

PMID- 23146199
TI  - Intended and unintended consequences of the gabapentin off-label marketing
      lawsuit among patients with bipolar disorder.
AB  - OBJECTIVE: The number of lawsuits accusing pharmaceutical companies of off-label
      marketing has risen in recent years. The impact of such lawsuits on drug
      prescribing and spending has not been examined. We evaluated a nationwide sample
      to determine whether the $430 million gabapentin off-label marketing lawsuit and
      accompanying media coverage affected gabapentin market share, substitution of
      other scientifically substantiated and unsubstantiated anticonvulsants, and
      anticonvulsant spending of Medicare/Medicaid patients diagnosed with bipolar
      disorder. METHOD: Using a national 5% sample of Medicare recipients linked to
      Medicaid claims, we used an interrupted times series design to evaluate the
      impact of the lawsuit on monthly market share, utilization, and spending from
      January 1, 2001, to December 31, 2005. RESULTS: The start of the lawsuit was
      associated with a 28% relative reduction in gabapentin market share (from ~ 21%
      to ~ 15%) and a reduction in the rate of prescribing from 108 prescriptions per
      1,000 patients per month before the start of the lawsuit to 90 by the end of
      follow-up (P < .001). We also observed increases in market share for 3 other
      anticonvulsants. Total anticonvulsant use and spending per 1,000 patients
      increased by 13% and 74%, respectively, after the intervention. The increase in
      anticonvulsant spending was equivalent to $7,554 per 1,000 patients per year
      higher than expected compared with the baseline trend (P = .01). CONCLUSIONS: We
      conclude that the lawsuit resulted in a reduction in gabapentin market share,
      increased market share for other anticonvulsants, and substantially increased
      total anticonvulsant spending to approximately half of the settlement amount, not
      counting substitutions of newer drugs for other illnesses affected by the
      lawsuit. These findings support the need for further study of the effects of
      current lawsuits regarding off-label drug marketing.

PMID- 23146202
TI  - Induction of superovulation in South American camelids.
AB  - The development of assisted reproductive technologies such as embryo transfer
      (ET), artificial insemination (AI) and in vitro fertilization (IVF) in South
      American camelids is considerably behind that of other livestock species. Poor
      success of the embryo transfer technique has been related to a lack of an
      effective superstimulatory treatment, low embryo recovery rate, and the recovery
      of hatched blastocysts that are not conducive to the cryopreservation process.
      Superstimulation has been attempted using equine chorionic gonadotropin (eCG) and
      follicle stimulating hormone (FSH) during the luteal, or the sexually receptive
      phase, sometimes given at follicular wave emergence. The rationale for inducing a
      luteal phase prior to or during superstimulation in camelids is not clearly
      understood, but it may simply reflect an empirical bias to conventional methods
      used in other ruminants. The number of ovulations or CL varies widely among
      studies, ranging from 2 to more than 15 per animal, with the number of
      transferable embryos ranging from 0 to 4 per animal. The control of follicular
      growth combined with superstimulatory protocols has resulted in a more consistent
      ovarian response and a greater number of follicles available for aspiration and
      oocyte collection. Recent studies in llamas have demonstrated that the use of
      ovulation inducing treatments or follicle ablation can synchronize follicular
      wave emergence allowing the initiation of gonadotropin treatment in the absence
      of a dominant follicle resulting in a more consistent ovulatory response. Few
      studies in alpacas have been reported, but it appears from recent field studies
      that the ovarian response is more variable and that there is a greater number of
      poor responders than in llamas. A review of superstimulation protocols that have
      been used in llamas and alpacas in the last 15 years is provided, including a
      discussion of the potential of protocols designed to initiate treatment at
      specific stages of follicular growth.

PMID- 23146203
TI  - Difficult-to-treat Gram-negative bone and joint infections: efficacy and safety
      of prolonged intravenous colistin.

PMID- 23146204
TI  - iMS2Flux--a high-throughput processing tool for stable isotope labeled mass
      spectrometric data used for metabolic flux analysis.
AB  - BACKGROUND: Metabolic flux analysis has become an established method in systems
      biology and functional genomics. The most common approach for determining
      intracellular metabolic fluxes is to utilize mass spectrometry in combination
      with stable isotope labeling experiments. However, before the mass spectrometric
      data can be used it has to be corrected for biases caused by naturally occurring
      stable isotopes, by the analytical technique(s) employed, or by the biological
      sample itself. Finally the MS data and the labeling information it contains have
      to be assembled into a data format usable by flux analysis software (of which
      several dedicated packages exist). Currently the processing of mass spectrometric
      data is time-consuming and error-prone requiring peak by peak cut-and-paste
      analysis and manual curation. In order to facilitate high-throughput metabolic
      flux analysis, the automation of multiple steps in the analytical workflow is
      necessary. RESULTS: Here we describe iMS2Flux, software developed to automate,
      standardize and connect the data flow between mass spectrometric measurements and
      flux analysis programs. This tool streamlines the transfer of data from
      extraction via correction tools to 13C-Flux software by processing MS data from
      stable isotope labeling experiments. It allows the correction of large and
      heterogeneous MS datasets for the presence of naturally occurring stable
      isotopes, initial biomass and several mass spectrometry effects. Before and after
      data correction, several checks can be performed to ensure accurate data. The
      corrected data may be returned in a variety of formats including those used by
      metabolic flux analysis software such as 13CFLUX, OpenFLUX and 13CFLUX2.
      CONCLUSION: iMS2Flux is a versatile, easy to use tool for the automated
      processing of mass spectrometric data containing isotope labeling information. It
      represents the core framework for a standardized workflow and data processing.
      Due to its flexibility it facilitates the inclusion of different experimental
      datasets and thus can contribute to the expansion of flux analysis applications.

PMID- 23146206
TI  - Ageing and the gut.
AB  - The goal of this brief review is to address the role of the ageing gut in the
      genesis of malnutrition in the elderly. We assess the burden of malnutrition in
      the elderly, exploring the role of comorbid conditions and neurohumoral changes
      that take place to contribute towards the process of anorexia associated with
      ageing. Following this, the review assesses physiological changes that occur in
      each part of the gastrointestinal (GI) tract and what implication they may have
      in clinical practice. In the oropharynx and the oesophagus, changes in swallowing
      and oesophageal motility associated with ageing can be demonstrated using
      physiological testing. However, in the absence of comorbid disease, they often
      have little, if any, clinical significance. In the stomach, reduced fundal
      compliance may contribute to early satiety; however, the primary change is
      hypochlorhydria, which may predispose to malabsorption or bacterial overgrowth
      further along the GI tract. Almost uniquely, the small bowel, particularly its
      absorptive function, is unaffected by age and we review the literature
      demonstrating this. In the colon, there is evidence of a prolonged transit time
      related to a reduction in both neurotransmitters and receptors. Although this may
      cause symptoms, this aspect is unlikely to contribute to malnutrition. In
      addition, we assess the potential changes in the gut microbiome and how this may
      interact with the immune system in the process of 'inflamm-ageing'. We conclude
      by summarising the main changes and their impact for the clinician along with
      recommendations for future areas of research.

PMID- 23146205
TI  - A novel control framework for nonlinear time-delayed dual-master/single-slave
      teleoperation.
AB  - A novel trilateral control architecture for the Dual-master/Single-slave
      teleoperation is proposed in this paper. This framework has been used in surgical
      training and rehabilitation applications. In this structure, the slave motion has
      been controlled by weighted summation of signals transmitted by the operator
      referring to task control authority through the dominance factors. The nonlinear
      dynamics for telemanipulators are considered which were considered as disregarded
      issues in previous studies of this field. Bounded variable time-delay has been
      considered which affects the transmitted signals in the communication channels.
      Two types of controllers have been offered and an appropriate stability analysis
      for each controller has been demonstrated. The first controller includes
      Proportional with dissipative gains (P+d). The second one contains Proportional
      and Derivative with dissipative gains (PD+d). In both cases, the stability of the
      trilateral control framework is preserved by choosing appropriate controller's
      gains. It is shown that these controllers attempt to coordinate the positions of
      telemanipulators in the free motion condition. The stability of the Dual
      master/Single-slave teleoperation has been proved by an appropriate Lyapunov like
      function and the stability conditions have been studied. In addition the proposed
      PD+d control architecture is modified for trilateral teleoperation with internet
      communication between telemanipulators that caused such communication
      complications as packet loss, data duplication and swapping. A number of
      experiments have been conducted with various levels of dominance factor to
      validate the effectiveness of the new control architecture.

PMID- 23146207
TI  - Benign familial neonatal convulsions caused by mutation in KCNQ3, exon 6: a
      European case.
AB  - Benign familial neonatal convulsions (BFNC) is a rare, clinically and genetically
      heterogenous epileptic disorder. Two voltage gated potassium genes, KCNQ2 and
      KCNQ3, have been identified as genes responsible for BFNC1 and BFNC2
      respectively. While as many as 73 mutations of KCNQ2 have been described up to
      date, only 4 mutations in KCNQ3, 3 of them appearing in exon 5, have been
      identified. Mutation in exon 6 was found for the first time in a Chinese family,
      and here we report the same missense mutation of KCNQ3 within exon 6 in a
      Caucasian family, whose history and clinical picture were in accordance with
      BFNC.

PMID- 23146208
TI  - Functional significance of a hepta nucleotide motif present at the junction of
      Cucumber mosaic virus satellite RNA multimers in helper-virus dependent
      replication.
AB  - Satellite RNAs (satRNA) associated with Cucumber mosaic virus (CMV) have been
      shown to generate multimers during replication. We have discovered that multimers
      of a CMV satRNA generated in the absence of its helper virus (HV) are
      characterized by the addition of a hepta nucleotide motif (HNM) at the monomer
      junctions. Here, we evaluated the functional significance of HNM in HV-dependent
      replication by ectopically expressing wild type and mutant forms of satRNA
      multimers in planta either in (+) or (-)-strand polarity. Comparative replication
      profiles revealed that (-)-strand multimers with complementary HNM (cHNM) are the
      preferred initial templates for HV-dependent replication than (-)-strand monomers
      and multimers lacking the cHNM. Further mutational analyses of the HNM accentuate
      that preservation of the sequence and native length of HNM is obligatory for
      efficient replication of satRNA. A model implicating the significance of HNM in
      HV-dependent production of monomeric and multimeric forms of satRNA is presented.

PMID- 23146209
TI  - A new virus from the plant pathogenic oomycete Phytophthora infestans with an 8
      kb dsRNA genome: the sixth member of a proposed new virus genus.
AB  - A virus designated Phytophthora infestans RNA virus 3 (PiRV-3) was characterized
      from an isolate of P. infestans that was co-infected with a second previously
      described virus, PiRV-4, a member of the virus family Narnaviridae (Cai et al.,
      2012). The genome of PiRV-3 is 8112 nt and one strand, designated the positive
      strand, has two deduced overlapping open reading frames linked by a potential
      frameshift sequence. The first open reading frame (ORF1) is predicted to encode a
      protein of unknown function, and ORF2 is predicted to encode an RNA-dependent RNA
      polymerase (RdRp) most closely related to six unclassified dsRNA viruses of
      filamentous fungi. The genome organizations of five of the related viruses are
      similar to PiRV-3, indicating taxonomic linkage among those viruses. We suggest
      that PiRV-3 and related viruses should be collected into a new virus taxon.

PMID- 23146210
TI  - Pituitary function and glucose tolerance in a family with a PAX6 mutation.
AB  - BACKGROUND: PAX6 is a transcription factor involved in the regulation of eye and
      islet cell development in humans and has also been shown to be an early marker of
      the pituitary gland in mice. While some subjects with PAX6 mutations were found
      to have impaired glucose tolerance or diabetes in two previous studies, there has
      been no report of systematic pituitary function assessment in these patients.
      AIM: The objective of this report was to assess pituitary function and glucose
      tolerance in five related patients with a heterozygous PAX6 mutation and an
      unusual ocular and neurological phenotype. SUBJECTS AND METHODS: Pituitary
      function (static and dynamic exploration of the five ante-pituitary axes) and
      glucose tolerance (oral glucose tolerance test) were explored in all patients.
      RESULTS: Glucose tolerance was normal in all patients. We found no obvious
      pituitary deficiency in four of the five patients. However, borderline cortisol
      levels were observed in three out of these patients, with subnormal values, at
      baseline and/or after stimulation test. Basal and stimulated cortisol levels were
      both more clearly diminished in one subject. CONCLUSIONS: We report here the
      first complete pituitary function assessment, together with glucose tolerance
      evaluations, in five related patients with a PAX6 mutation. We cannot rule out
      subtle corticotrope deficiency induced by PAX6 mutation. The conflicting results
      with the literature about glucose tolerance could be explained by
      genotype/phenotype correlations.

PMID- 23146211
TI  - The natural history of moyamoya in a North American adult cohort.
AB  - Moyamoya disease and moyamoya syndrome (MMD/S) are a considerable source of
      neurologic morbidity in adults as a result of both ischemic and hemorrhagic
      events. Unfortunately, there is a paucity of literature detailing the natural
      course of MMD/S in the USA. To elucidate epidemiological information, stroke
      rates, hemorrhage rates, and risk factors for these events in patients with
      MMD/S, we reviewed our own institutional cohort of 42 North American adults with
      MMD/S. The mean patient age was 38.8 (standard deviation [SD] 12.7) with a 5:1
      female-to-male predominance. About 74% of patients had an ischemic presentation
      while only 17% presented with hemorrhage. The mean Suzuki grade was higher in
      patients presenting with hemorrhage (3.7 compared to 2.9, p=0.03) but similar in
      those who presented with a stroke as compared to those who did not (3.00 compared
      to 3.05, p=0.88). The overall annual stroke and hemorrhage rates were 13.3% and
      1.7%, respectively. Statistically significant risk factors for stroke or
      hemorrhage were female sex (p=0.031) and stroke presentation within 3 years
      (hazard ratio [HR]=4.08, p=0.035). Smoking was another risk factor, but it did
      not meet statistical significance (HR=1.56, p=0.38). We conclude that these
      results favor intervention for MMD/S to mitigate the high annual stroke risk.
      This particularly applies to females and/or those presenting with a recent
      stroke/hemorrhage. Our results also serve as a baseline for comparison of
      hemorrhage rates after intervention.

PMID- 23146212
TI  - The advantages of balloon assistance in endovascular embolization of spinal dural
      arteriovenous fistulas.
AB  - Endovascular embolization is accepted as an alternative to surgical management of
      spinal dural arteriovenous fistulas (DAVF) in most patients; however, when the
      feeder vessel arises from the trunk vessel with an acutely angled origin,
      microcatheter navigation may be difficult, hazardous, and sometimes impossible.
      We propose a technique that eases microguidewire engagement and
      microcatheterization of arteries that arise at very acute angles with the
      assistance of a parallel compliant balloon that acts as supporter, guider, and
      protector. This technique was successfully applied in three consecutive patients
      with spinal DAVF with unfavorable vascular anatomy that limited selective
      microcatheterization. The balloon supports and guides the microguidewire along
      the feeder (supportive role). The balloon can then be placed at the origin of the
      feeder vessel and inflated during embolization to prevent liquid agent reflux
      (protective role). Use of this technique as a first option reduces procedure time
      and radiation exposure. A limiting factor is the need for a relatively large
      working channel to allow the combined use of a balloon and a microcatheter.

PMID- 23146213
TI  - Cobalamin as a regulator of serum and cerebrospinal fluid levels of normal
      prions.
AB  - We have previously demonstrated that the concentration of normal prion proteins
      (PrP(C)) is increased in the serum and cerebrospinal fluid (CSF) of rats
      deficient in vitamin B(12) (cobalamin, Cbl). In this study, we investigated
      whether similar increases also occur in the serum and CSF of patients deficient
      in Cbl (Cbl-D), and whether the increase in serum levels can be corrected by Cbl
      therapy. The study involved two sample populations. The first consisted of 45
      patients (13 patients with pernicious anemia [PA], 19 with other forms of anemia,
      and 13 healthy controls); and the second, 68 patients (five with subacute
      combined degeneration [SCD], 18 with amyotrophic lateral sclerosis, 22 with
      multiple sclerosis [MS], and 23 neurological controls). Serum PrP(C) levels were
      measured using an enzyme-linked-immunosorbent-assay before as well as after Cbl
      therapy. The mean serum PrP(C) levels in patients with PA were significantly
      higher than those of the controls (p=0.0017) but normalized after Cbl therapy;
      there was no significant change in the patients with other forms of anemia. Mean
      CSF PrP(C) levels in the patients with SCD were significantly higher than in the
      neurological controls (p<0.03). The serum and CSF PrP(C) levels of patients with
      PA and those with SCD were correlated significantly with serum (p=0.004) and CSF
      (p=0.0018) Cbl levels. In patients with MS, CSF PrP(C) concentrations were
      significantly lower than those of the controls regardless of their CSF Cbl
      levels. We found a correlation between Cbl and PrP(C) levels in the serum and CSF
      of Cbl-D patients, which suggests that Cbl may regulate the PrP(C) levels in the
      serum and CSF in humans.

PMID- 23146214
TI  - Auxin signal transcription factor regulates expression of the brassinosteroid
      receptor gene in rice.
AB  - The phytohormones auxins and brassinosteroids are both essential regulators of
      physiological and developmental processes, and it has been suggested that they
      act inter-dependently and synergistically. In rice (Oryza sativa), auxin co
      application improves the brassinosteroid response in the rice lamina inclination
      bioassay. Here, we showed that auxins stimulate brassinosteroid perception by
      regulating the level of brassinosteroid receptor. Auxin treatment increased
      expression of the rice brassinosteroid receptor gene OsBRI1. The promoter of
      OsBRI1 contains an auxin-response element (AuxRE) that is targeted by auxin
      response factor (ARF) transcription factors. An AuxRE mutation abolished the
      induction of OsBRI1 expression by auxins, and OsBRI1 expression was down
      regulated in an arf mutant. The AuxRE motif in the OsBRI1 promoter, and thus the
      transient up-regulation of OsBRI1 expression caused by treatment with indole-3
      acetic acid, is essential for the indole-3-acetic acid-induced increase in
      sensitivity to brassinosteroids. These findings demonstrate that some ARFs
      control the degree of brassinosteroid perception required for normal growth and
      development in rice. Although multi-level interactions between auxins and
      brassinosteroids have previously been reported, our findings suggest a mechanism
      by which auxins control cellular sensitivity to brassinosteroids, and further
      support the notion that interactions between auxins and brassinosteroids are
      extensive and complex.

PMID- 23146215
TI  - Use of miglustat in a child with late-infantile-onset Niemann-Pick disease type C
      and frequent seizures: a case report.
AB  - INTRODUCTION: Niemann-Pick disease type C is a rare genetic lysosomal storage
      disease associated with impaired intracellular lipid trafficking and a range of
      progressive neurological manifestations. The influence of seizure activity on
      disease course and response to miglustat therapy is not currently clear. CASE
      PRESENTATION: Niemann-Pick disease type C homozygous for NPC1 mutation p.S940L
      [c. 2819 C>T] was diagnosed in a four-and-a-half-year-old Norwegian Caucasian
      girl. The patient, who died at eight years and seven months of age, had a history
      of prolonged neonatal jaundice and subsequently displayed progressive
      neurological manifestations that started with delayed speech, ataxia, and
      gelastic cataplexy. A regimen of 100mg of miglustat three times a day was
      initiated when she was four years and 11 months old. She showed decreased
      neurological deterioration during about three and a half years of treatment.
      However, she displayed periods of distinct worsening that coincided with frequent
      epileptic seizures. Anti-epileptic therapy reduced seizure frequency and severity
      and allowed re-stabilization of her neurological function. Prior to her death,
      which was possibly due to acute cardiac arrest, seizure activity was well
      controlled. CONCLUSIONS: Miglustat delayed the expected deterioration of
      neurological function in this patient with p.S940L-homozygous late-infantile
      onset Niemann-Pick disease type C and provided important quality-of-life
      benefits. This case demonstrates the importance of effective seizure control
      therapy in achieving and maintaining neurological stabilization in Niemann-Pick
      disease type C.

PMID- 23146217
TI  - Foodborne cryptosporidiosis: is there really more in Nordic countries?
AB  - Most waterborne outbreaks of cryptosporidiosis are reported from the USA, and in
      Europe from the UK. However, since 2000 reports of foodborne cryptosporidiosis
      seem to be skewed towards Nordic countries, although consumers in these countries
      are apparently less concerned about microbiological contamination of food than
      consumers elsewhere. Possible reasons for this unexpected geographical
      distribution might include prolonged survival of oocysts in the Nordic climate,
      greater exposure due to elevated consumption of higher-risk products (possibly
      including imported foods), and better outbreak investigation and reporting.
      Although the risk of foodborne cryptosporidiosis is probably underestimated
      globally, we suggest that the next outbreak is no more likely to be in a Nordic
      country than anywhere else.

PMID- 23146216
TI  - Platinum chemotherapy for BRCA1-related breast cancer: do we need more evidence?
AB  - A recent prospective clinical trial provides further evidence that breast cancers
      arising in germline BRCA1 mutation carriers are highly sensitive to cisplatin
      chemotherapy. The potential significance of these data for the management of
      patients with BRCA1-related and BRCA2-related breast cancer is discussed. 

PMID- 23146220
TI  - Rapid at-line pharmaceutical cleaning verification using a novel light induced
      fluorescence (LIF) sensor.
AB  - A novel light emitting diode (LED) array-based light induced fluorescence (LIF)
      sensor is presented as an analytical methodology for at-line cleaning
      verification within the pharmaceutical industry. This sensor differs from
      conventional LIF sensors through the ability to dynamically control both the LED
      excitation array and detection parameters, enabling the exploitation of the
      optical power and detection sensitivity to rapidly detect trace concentrations of
      residual drug. This feature makes this sensor an ideal alternative to
      conventional cleaning verification analytical methodologies. In this study, the
      LIF sensor was validated as an analytical technique through the analysis of
      specificity, precision, linearity, limit of quantitation, and accuracy, with
      respect to solutions and swab extracts of a single pharmaceutical compound
      (Compound A). The validated system was then utilized for cleaning process
      optimization and subsequent routine cleaning process verification following three
      manufacturing campaigns. The LIF sensor enabled a significant improvement in the
      analysis time for quantitative detection of Compound A; individual swab and
      rinsate extracts were analyzed in less than 1 min. The results presented herein
      effectively demonstrate the ability of the novel LIF sensor to efficiently
      function as a valid at-line analytical methodology for cleaning verification.

PMID- 23146221
TI  - Simple LC-MS/MS methods for simultaneous determination of pitavastatin and its
      lactone metabolite in human plasma and urine involving a procedure for inhibiting
      the conversion of pitavastatin lactone to pitavastatin in plasma and its
      application to a pharmacokinetic study.
AB  - Sometimes, drugs and their metabolites in plasma may convert to each other. This
      phenomenon is called interconversion, which may result in the instability problem
      of the plasma samples. The instability problem caused by interconversion of the
      co-existing metabolites may often be ignored, since there is no drug metabolite
      in the quality control samples prepared for method validation. Pitavastatin
      lactone (Pi-LAC), a main metabolite of pitavastatin (Pi), is very unstable and
      easily converted to Pi in plasma. In this paper, simple and rapid LC-ESI-MS/MS
      methods were developed for the simultaneous determination of Pi and Pi-LAC in
      human plasma and urine. The sample stability was examined under different
      conditions. The interconversion of Pi and Pi-LAC was prevented by adding a pH 4.2
      buffer solution to the freshly collected plasma samples. Detection was performed
      using an electrospray ionization (ESI) operating in positive ion multiple
      reaction monitoring mode by monitoring the ion transitions from m/z 422.2->290.3
      (Pi), 404.2->290.3 (Pi-LAC) and m/z 611.3->423.2 (candesartan cilextetil, the
      internal standard), respectively. The calibration curve of Pi and Pi-LAC in both
      human plasma and urine showed good linearity over the concentration range of 0.1
      200 ng/mL. The established methods were successfully applied to a pharmacokinetic
      study of pitavastatin calcium tablets in healthy Chinese volunteers after oral
      administration of 1, 2 and 4 mg single and multiple doses of pitavastatin
      calcium. The pharmacokinetic parameters of Pi and Pi-LAC in Chinese volunteers
      were given respectively. The urinary excretion profiles of Pi and Pi-LAC in
      Chinese volunteers were also presented. After receiving a single 4 mg oral dose
      of pitavastatin calcium, the average cumulative urinary excretion percentages of
      Pi and Pi-LAC in Chinese volunteers were (0.41 +/- 0.16)% and (6.1 +/- 5.0)%,
      respectively.

PMID- 23146222
TI  - The development and validation of an immunoassay for the measurement of anti
      thymidine phosphorylase antibodies in mouse and dog sera.
AB  - Erythrocyte encapsulated thymidine phosphorylase (EE-TP) is under development as
      an enzyme replacement therapy for mitochondrial neurogastrointestinal
      encephalomyopathy (MNGIE), a fatal metabolic disorder resulting from an inherited
      deficiency of the enzyme thymidine phosphorylase. We report here the development
      and validation of a sensitive electrochemiluminescent (ECL) bridging immunoassay
      to support Good Laboratory Practice (GLP)-compliant preclinical safety studies of
      EE-TP in the mouse and dog. Affinity-purified rabbit anti-E. coli thymidine
      phosphorylase (TP) antibody was used as a calibrator standard with an effective
      working range of 2.5-7500 ng/mL. The minimum required dilution (MRD) for both
      mouse and dog sera was 1:10. The mean analytical recoveries for anti-TP
      antibodies spiked into serum at 70 ng/mL and 7000 ng/mL were 117.9% and 93.2%,
      respectively for mouse, and 112.0% and 104.3%, respectively for dog. The intra
      assay precision (coefficient of variation, CV) ranged between 1.1% and 8.0% in
      mouse serum, and 1.9% and 2.5% in dog serum. Inter-assay precision ranged between
      -1.6% and 6.7% in mouse serum, and -13.0% and -2.5% in dog serum. Assay cut
      point/screening cut-point correction factors were 201.37 and 44.4, respectively
      for mouse and dog sera. For future analysis of positive test samples, less than
      37.12% (mouse) and 31.41% (dog) inhibition of the assay signal in the
      confirmation assay will confer anti-TP antibody specificity. Assay drift and hook
      effects (prozone) were not observed. The intra-assay and inter-assay accuracy for
      robustness were within +/-20%.

PMID- 23146223
TI  - Evaluation of core-shell particle columns for ion-pair reversed-phase liquid
      chromatography analysis of oligonucleotides.
AB  - An investigation into the use of core-shell particle columns for separation of
      short (~21 base pairs) RNA oligonucleotides by ion-pair reversed-phase liquid
      chromatography (IP-RPLC) showed improved resolution for a number of test analytes
      relative to conventional (fully-porous) reversed-phase columns. The best
      resolutions were obtained using columns packed with smaller sub-2MUm core-shell
      particles.

PMID- 23146224
TI  - Quality control of Lonicerae Japonicae Flos using near infrared spectroscopy and
      chemometrics.
AB  - A set of qualitative and quantitative methods based on near infrared (NIR)
      spectroscopy was established for the geographical origin identification,
      quantitative determination of active compounds, and fingerprint analysis of
      Lonicerae Japonicae Flos. The spectra of 140 samples from different origins were
      collected with two NIR instruments from different manufacturers (Thermo
      Scientific and Buchi). A Soft Independent Modeling of Class Analogy model was
      established for the identification of Lonicerae Japonicae Flos from the genuine
      producing area. Using the established discriminant analysis model, 22 samples
      from Henan province were predicted with 100% rate of accuracy, while the 68
      samples from other producing areas were predicted with 9 samples incorrectly
      judged. Futhermore, partial least square regression method was used for
      developing the quantitative calibration models with the reference values
      determined with a validated HPLC-UV method. The RMSEP values of external
      validation are 0.169%, 0.048%, 0.172%, 0.007%, 0.203%, and 0.066% for NCA, CA,
      CfA, 3,4-DCA, 3,5-DCA, and 4,5-DCA, respectively, which indicated that the
      established models possess satisfactory predictive abilities. In addition, the
      models established on the primary instrument can also be transferred to the
      secondary instrument using direct standardization algorithm, which enlarged the
      application scope of the established models. Since the NIR spectra can reflect
      the comprehensive quality information of Lonicerae Japonicae Flos, a fingerprint
      analysis method was finally proposed for the quality consistency check of raw
      materials. The proposed methods are rapid and effective, and possess good
      portability, which is helpful to the quality control of Lonicerae Japonicae Flos.

PMID- 23146225
TI  - Development and validation of RP-UPLC method for the determination of darifenacin
      hydrobromide, its related compounds and its degradation products using design of
      experiments.
AB  - A selective stability-indicating ultra-performance liquid chromatographic (UPLC)
      method was developed for the quantitative determination of darifenacin
      hydrobromide (DFN) and its related compounds in API and pharmaceutical dosages.
      The chromatographic separation was achieved on an Acquity UPLC BEH C18 column
      (100, 2.1 mm and 1.7 MUm) at a flow rate of 0.3 mL/min, and detection was
      performed at 210 nm. The typical retention behaviors of impurities at various pH
      values were depicted graphically. The LC conditions were optimized by design of
      experiments (DOE) to obtain optimal separation in the shortest possible run time.
      A central composite design (CCD) was employed to study the main effects and
      interactions of the independent variables. The drug and its thirteen impurities
      were eluted within 13 min. The method exhibited consistent, high-quality
      recoveries (93.8 +/- 2.1 to 99.8 +/- 1.5 (mean +/- RSD)) with a high precision
      for the drug and impurities. Linear regression analysis revealed an excellent
      correlation between peak responses and concentrations (R(2) values of 0.9991
      0.9999) for the drug and impurities. The stability-indicating capability of the
      method was verified by forced degradation experiments and mass balance study. LC
      MS revealed protonated molecular ion peaks [M+H](+) at m/z 428.20, m/z 425.20 and
      m/z 281.30 for the acid (Imp-4), oxidized (Imp-6) and N-dealkylated (Imp-1) forms
      of DFN, respectively. Possible degradation pathways were established based on the
      known reactivity of the drug through hydrolysis, oxidation, N-dealkylation,
      phenyl hydroxylation, dihydrobenzofuran ring hydroxylation and ring opening. The
      m/z values of unknown degradation products were matched with the proposed
      structures and reported DFN metabolites.

PMID- 23146226
TI  - Simultaneous acquisition of the dissolution curves of two active ingredients in a
      binary pharmaceutical association, employing an on-line circulation system and
      chemometrics-assistance.
AB  - The association of an on-line circulation system with a chemometrics-assisted UV
      detection strategy is described as a useful system to continuously monitor the
      dissolution of a pharmaceutical preparation containing two active ingredients,
      and as a tool for the simultaneous determination of the dissolution curves and
      dissolution profiles of the latter. Multivariate curve resolution with
      alternating least squares (MCR-ALS) was used as the chemometric tool to
      quantitate the analytes, while the hydrochlorothiazide-bisoprolol fumarate (HCT
      BIS) association was employed as a model for method development. The experiments
      were carried out with a dissolution tester configured as apparatus II (paddles),
      under USP 32 official conditions. The suitability of the calibration procedure
      for quantitating the dissolved drugs was assessed according to ICH guidelines,
      with regards to linearity in the working range, specificity, accuracy and
      precision. Figures of merit, including limits of detection and quantitation were
      also determined, as well as the method's robustness with regards to detection
      wavelength range. The system was able to consistently provide very reproducible
      dissolution curves of commercial tablets, which were statistically similar to
      those furnished by a manual sampling technique, followed by HPLC analysis. To
      demonstrate the usefulness of the proposed system, the dissolution profiles of
      different lots of HCT-BIS tablets were acquired and three of them were
      conveniently compared at a 31 data point level, employing the f(1) and f(2)
      ("difference" and "similarity") indexes. Use of multiple data points for
      comparison ensured reliability of the results.

PMID- 23146227
TI  - Analysis and characterization of aggregation of a therapeutic Fc-fusion protein.
AB  - Protein aggregation was observed in a purification intermediate of a therapeutic
      Fc-fusion protein stored at -30  degrees C, even though the protein was stable at
      4 and -80  degrees C. The protein was expressed in Escherichia coli as an
      inclusion body, refolded, and purified using chromatography columns. To study the
      nature of this aggregation, a series of experiments were conducted to investigate
      factors that contributed to the protein instability during freezing. We found
      that the presence of free thiols in the protein is the intrinsic cause. The free
      thiol cross-linking sites were determined to be at the peptide moiety of the Fc
      fusion protein using LC-MS. Partially frozen accompanied by the elevated pH and
      increased salt and protein concentrations were identified as extrinsic factors
      that facilitated the aggregation. These results provided important insights into
      purification process improvement and solution storage of this Fc-fusion protein.

PMID- 23146228
TI  - Chromatographic retention parameters in correlation analysis with in silico
      biological descriptors of a novel series of N-phenyl-3-methyl succinimide
      derivatives.
AB  - Reversed-phase thin-layer chromatographic (RP TLC) retention coefficients for a
      newly designed series of N-phenyl-3-methyl succinimide derivatives, of a
      rationally expected anticonvusant activity, were determined as parameters of
      their lipophilicity. Basic pharmacokinetic descriptors of the agents were
      calculated in silico with the use of the established medicinal chemistry/drug
      design software. Highly significant, predictive relationships were found between
      the chromatographic retention constants and the bioactivity descriptors, which
      are assumed to account for drug absorption, distribution, elimination and
      toxicity (ADMETox) in humans. Among the agents investigated, the compounds with
      halogen substituent (Compounds nos. 9-13 in Fig. 1), were identified as the best
      drug candidates, because of their predicted proper pharmacokinetics, and have
      been selected for further research and development studies on new antiepileptic
      drugs. At the same time, among the congeners studied these can be indicated,
      which should not be rationally subjected to bioactivity tests.

PMID- 23146229
TI  - In vivo study on the monoamine neurotransmitters and their metabolites change in
      the striatum of Parkinsonian rats by liquid chromatography with an acetylene
      black nanoparticles modified electrode.
AB  - The variation in the concentration of monoamine neurotransmitters and their
      metabolites in an experimental Parkinsonian animal model established by
      unilateral 6-hydroxydopamine administration was studied. For the purpose of
      detecting monoamine neurotransmitters and their metabolites more sensitively, an
      acetylene black nanoparticles modified electrode was fabricated and used as the
      working electrode for an electrochemical detector in HPLC. The results indicated
      that the modified electrode exhibited efficiently electrocatalytic oxidation for
      monoamine neurotransmitters and their metabolites with relatively high
      sensitivity, long life, and stability. The linear ranges spanned four orders of
      magnitude (r>0.998) and the detectability was on the level of 0.1 nmolL(-1). The
      percent relative standard deviation (%RSD) for each compound at all concentration
      levels was lower than 2.57% and 1.94% for intra-day and inter-day precision,
      respectively. The mean recovery values were between 98.75% and 105.25%, and the
      %RSD was found to be less than 1.02%. Coupled with in vivo microdialysis
      sampling, the validated method was successfully applied to measure monoamine
      neurotransmitters and their metabolites in both sides of the striatum of
      conscious and freely moving Parkinsonian rats, and the extracellular monoamine
      neurotransmitters and their metabolites in the lesioned-side striatum of
      unilateral 6-hydroxydopamine-lesioned rats were lower than that in the intact
      side striatum or in the striatum of control rats.

PMID- 23146230
TI  - Development and validation of liquid chromatography-tandem mass spectrometry
      method for simultaneous determination of four tertiary alkaloids in rat plasma
      and its application to a pharmacokinetic study.
AB  - A specific and reliable liquid chromatography-electrospray ionization-tandem mass
      spectrometry method was developed for the simultaneous determination of
      tetrahydropalmatine (THP), tetrahydroberineper (THB), tetrahydrocoptisine (THC)
      and corydaline (CDL) in rat plasma using jatrorrhizine as internal standard.
      Plasma samples were pretreated by protein precipitation with acetonitrile.
      Chromatographic separation was performed on a Zorbax Eclipse Plus C18 column (3.0
      mm * 100 mm, 1.8 MUm) with gradient elution using acetonitrile-0.1% formic acid
      water as mobile phase at a flow rate of 0.3 mL/min. The detection was carried out
      by a triple-quadrupole tandem mass spectrometer in multiple-reaction monitoring
      mode. The mass transition ion-pair was followed as m/z 356.2->192.1, m/z 324.1
      >176.0, m/z 340.1->176.0, and m/z 370.3->192.1 for THP, THC, THB and CDL. Linear
      calibration curves were obtained over the range of 0.2-2000 ng/mL, and the method
      limits were 2.0 ng/mL for THC, 0.2 ng/mL for THB, 1.0 ng/mL for THP, and 0.4
      ng/mL for CDL, respectively. The mean recovery of the analytes ranged from 85.51%
      to 93.99%. The intra- and inter-day precisions were in the range of 1.21-4.73%
      and the accuracies were between 92.23% and 98.23%. The validated method was
      successfully applied to a pharmacokinetic study of THP, THB, THC and CDL in rat
      plasma following oral administration of Jitai tablet.

PMID- 23146231
TI  - LC-ESI-MS quali-quantitative determination of phenolic constituents in different
      parts of wild and cultivated Astragalus gombiformis.
AB  - High-performance liquid chromatography electrospray ionization mass spectrometry
      (LC-ESI-MS) profiling of the MeOH extract of Astragalus gombiformis Pomel
      (Fabaceae) aerial parts guided the isolation of seven phenolic compounds among
      which 7-methylquercetin 3-O-alpha-l-rhamnopyranosyl-(1->2)-beta-D
      galactopyranoside (2) and 7-methylquercetin 3-O-alpha-L-rhamnopyranosyl-(1->2)-[6
      O-(3-hydroxy-3-methylglutaryl)-beta-D-galactopyranoside] (7) whose structures
      were elucidated by NMR and ESI-MS experiments. The radical scavenging activities
      of isolated compounds were investigated, by using the TEAC assay. Furthermore
      quantitative analyses were performed by LC-ESI-MS and applied to the comparative
      profiling of different parts (aerial parts, leaves and stems) of cultivated and
      wild A. gombiformis samples, confirming the interest of these compounds as
      markers of the species. Finally, a Principal Component Analysis was carried out
      in order to highlight the differences between different parts of cultivated and
      wild plants.

PMID- 23146232
TI  - Rapid characterization of chemical constituents and rats metabolites of the
      traditional Chinese patent medicine Gegen-Qinlian-Wan by UHPLC/DAD/qTOF-MS.
AB  - Gegen-Qinlian-Wan (GQW) is a popular traditional Chinese patent medicine for the
      treatment of diarrhea. It is composed of four herbal medicines, Puerariae Radix,
      Scutellariae Radix, Coptidis Rhizoma, and Glycyrrhizae Radix. In this study, a
      rapid and sensitive method based on ultra high-performance liquid chromatography
      coupled with diode-array detection and quadrupole time-of-flight mass
      spectrometry (UHPLC-DAD-qTOF-MS) was established to characterize the chemical
      constituents and rats metabolites of GQW. Samples were separated on an Agilent
      Zorbax Eclipse Plus-C(18) column (100 mm * 2.1 mm, 1.8 MUm) by gradient elution
      using acetonitrile and water containing 0.1% formic acid as the mobile phase. On
      the basis of UV and qTOF high-accuracy mass spectral analysis, a total of 62
      compounds were identified or tentatively characterized from GQW, including 42
      flavonoids, 8 alkaloids, 6 triterpenoids, 3 phenylethanoid glycosides, and 3
      other types. Among them, 27 compounds were confirmed by comparing with reference
      standards. Furthermore, metabolites in rats plasma and urine after oral
      administration of GQW were also analyzed. A total of 42 compounds were
      identified, including 29 prototypes and 13 metabolites through metabolic pathways
      of demethylation, methylation, hydrolysis, sulfate conjugation, and glucuronide
      conjugation. Glucuronidated flavonoids were the main constituents in the plasma,
      and were then transformed into aglycones and excreted from urine. This is the
      first systematic study on the chemical constituents and metabolic profiling of
      GQW.

PMID- 23146233
TI  - Serum metabonomics coupled with Ingenuity Pathway Analysis characterizes
      metabolic perturbations in response to hypothyroidism induced by propylthiouracil
      in rats.
AB  - A serum metabonomic profiling method based on ultra-performance liquid
      chromatography/time-of-flight mass spectrometry (UHPLC/TOF-MS) was applied to
      investigate the metabolic changes in hypothyroid rats induced by propylthiouracil
      (PTU). With Significance Analysis of Microarray (SAM) for classification and
      selection of biomarkers, 13 potential biomarkers in rat serum were screened out.
      Furthermore, Ingenuity Pathway Analysis (IPA) was introduced to deeply analyze
      unique pathways of hypothyroidism that were primarily involved in sphingolipid
      metabolism, fatty acid transportation, phospholipid metabolism and phenylalanine
      metabolism. Our results demonstrated that the metabonomic approach integrating
      with IPA was a promising tool for providing a novel methodological clue to
      systemically dissect the underlying molecular mechanism of hypothyroidism.

PMID- 23146234
TI  - Quantification of trans-2,6-difluoro-4'-N,N-dimethylaminostilbene in rat plasma:
      application to a pharmacokinetic study.
AB  - trans-2,6-Difluoro-4'-N,N-dimethylaminostilbene (DFS), a synthetic stilbene,
      displayed potent pre-clinical anti-cancer activities exceeding that observed for
      naturally occurring resveratrol. In this study, a simple and sensitive HPLC
      method was developed and validated to quantify DFS in rat plasma. The lower limit
      of quantification (LLOQ) was 5 ng/ml. The intra- and inter-day variation in terms
      of relative standard deviation (RSD) was all less than 10%. The bias rate ranged
      from -11.5% to 6.2% while the absolute recovery ranged from 94.1 +/- 2.3 to 97.3
      +/- 4.4%. The pharmacokinetic profiles of DFS were examined in Sprague-Dawley
      rats after intravenous administration (2 mg/kg). DFS displayed moderate clearance
      (Cl=61.5 +/- 17.7 ml/min/kg) and a relatively prolonged terminal elimination half
      life (t(1/2 lambdaz)) of 351 +/- 180 min. Aqueous solubility played a crucial
      role in the oral absorption of DFS. When DFS was given as a suspension (6 mg/kg),
      the absolute oral bioavailability (F) was almost negligible. However, when DFS
      was given in a solution prepared with hydroxypropyl-beta-cyclodextrin (6 mg/kg),
      the F was 12.4 +/- 10.7%. Dose-escalation to 15 mg/kg resulted in much higher
      systemic exposure (F=40.2 +/- 10.0%). As DFS is orally available after
      formulation with hydroxypropyl-beta-cyclodextrin and pharmacologically active
      systemic concentrations could be achieved after a single oral dose, the use of
      DFS as a cancer chemopreventive/chemotherapeutic agent is possible.

PMID- 23146235
TI  - A metabolite-profiling approach to assess the uptake and metabolism of phenolic
      compounds from olive leaves in SKBR3 cells by HPLC-ESI-QTOF-MS.
AB  - Olive leaves, an easily available natural low-cost material, constitute a source
      of extracts with significant antitumor activity that inhibits cell proliferation
      in several breast-cancer-cell models. In this work, a metabolite-profiling
      approach has been used to assess the uptake and metabolism of phenolic compounds
      from an olive-leaf extract in the breast-cancer-cell line SKBR3 to evaluate the
      compound or compounds responsible for the cytotoxic activity. For this, the
      extract was firstly characterized quantitatively by high-performance liquid
      chromatography coupled to electrospray ionization-quadrupole time-of-flight mass
      spectrometry (HPLC-ESI-QTOF-MS). Then, SKBR3 cells were incubated with 200 MUg/mL
      of the olive-leaf extract at different times (15 min, 1, 2, 24, and 48 h). A
      metabolite-profiling approach based on HPLC-ESI-QTOF-MS was used to determine the
      intracellular phenolic compounds, enabling the identification of 16 intact
      phenolic compounds from the extract and four metabolites derived from these
      compounds in the cell cytoplasm. The major compounds found within the cells were
      oleuropein, luteolin-7-O-glucoside and its metabolites luteolin aglycone and
      methyl-luteolin glucoside, as well as apigenin, and verbascoside. Neither
      hydroxytyrosol nor any of its metabolites were found within the cells at any
      incubation time. It is proposed that the major compounds responsible for the
      cytotoxic activity of the olive-leaf extract in SKBR3 cells are oleuropein and
      the flavones luteolin and apigenin, since these compounds showed high uptake and
      their antitumor activity has been previously reported.

PMID- 23146236
TI  - UFLC-MS/MS method for simultaneous determination of luteolin-7-O-gentiobioside,
      luteolin-7-O-beta-D-glucoside and luteolin-7-O-beta-D-glucuronide in beagle dog
      plasma and its application to a pharmacokinetic study after administration of
      traditional Chinese medicinal preparation: Kudiezi injection.
AB  - A rapid, sensitive and selective ultra-fast liquid chromatography-tandem mass
      spectrometry (UFLC-MS/MS) method for the simultaneous determination of three
      active flavonoid glycosides: luteolin-7-O-gentiobioside, luteolin-7-O-beta-D
      glucoside and luteolin-7-O-beta-D-glucuronide in beagle dog plasma was developed
      and validated. Puerarin was used as internal standard (IS). After protein
      precipitation with acidified acetonitrile, the analytes were separated on a
      Venusil MP C18 column with a gradient elution system composed of 0.05% formic
      acid and acetonitrile at a flow rate of 0.4ml/min. Detection was performed using
      multiple reaction monitoring (MRM) mode with a turbo ion spray source under a
      negative ionization condition. The calibration curves of the three analytes
      showed good linearity (r>0.995) within the tested concentration ranges. The lower
      limits of quantification for luteolin-7-O-gentiobioside, luteolin-7-O-beta-D
      glucoside and luteolin-7-O-beta-D-glucuronide were 1.0 ng/ml, 1.0 ng/ml and 4.0
      ng/ml, respectively. The intra-day and inter-day precision and accuracy
      deviations were less than 15%, and the extraction recoveries of the three
      analytes from beagle dog plasma were more than 75%. The validated method was
      successfully applied to a pharmacokinetic study of the three flavonoid glycosides
      in beagle dog plasma after intravenous administration of the traditional Chinese
      medicinal preparation: Kudiezi injection.

PMID- 23146237
TI  - The artifactual nature of stavudine binding to human serum albumin. A
      fluorescence quenching and isothermal titration calorimetry study.
AB  - The interaction between stavudine, a nucleoside reverse transcriptase inhibitor
      and human serum albumin (HSA), was investigated by fluorescence quenching
      technique and isothermal titration calorimetry (ITC). A good linearity of albumin
      fluorescence quenching in the presence of stavudine was determined. Analyzing
      these data we obtained for the dissociation constant the value K(d)=(18.18 +/-
      0.46) * 10(-5)M. However, due to contradictory results obtained in ITC
      experiments, we checked the fluorescence quenching data for the inner-filter
      effect, the main confounding factor in the observed quenching. Based on the UV
      vis absorption data we have corrected the observed fluorescence intensities and
      concluded, in accordance with ITC results, that stavudine binding to HSA is
      negligible and the observed quenching effect is entirely caused by a failure to
      correct for the inner-filter effect.

PMID- 23146238
TI  - LC-Q/TOF mass spectrometry data driven identification and spectroscopic
      characterisation of a new 3,4-methylenedioxy-N-benzyl cathinone (BMDP).
AB  - The recent increase in the sell and abuse of substituted cathinones has developed
      the requirement for fast and reliable screening methods for these compounds in
      legal high products. This paper shows an example of the successful application of
      liquid chromatography-high resolution quadrupole time-of-flight mass spectrometry
      to detection and identification of a new synthetic cathinone 3,4-methylenedioxy-N
      benzylcathinone (BMDP) in legal high samples. It discusses the mass
      spectrometric, the nuclear resonance spectroscopic and infrared spectroscopic
      data of BMDP. BMDP was first seized in United Kingdom in 2010, it was also seized
      in Poland in winter of 2010. The structure elucidation of the drug was carried
      out by high resolution product ion spectrometry after collision induced
      dissociation, and the product ion spectrometry after electron ionisation and one
      and two-dimensional (1)H NMR and (13)C NMR spectroscopy supported the findings.

PMID- 23146239
TI  - Direct high-performance liquid chromatography method with refractometric
      detection designed for stability studies of treosulfan and its biologically
      active epoxy-transformers.
AB  - Treosulfan (TREO) is an alkylating agent registered for treatment of advanced
      platin-resistant ovarian carcinoma. Nowadays, TREO is increasingly applied iv in
      high doses as a promising myeloablative agent with low organ toxicity in
      children. Under physiological conditions it undergoes pH-dependent transformation
      into epoxy-transformers (S,S-EBDM and S,S-DEB). The mechanism of this reaction is
      generally known, but not its kinetic details. In order to investigate kinetics of
      TREO transformation, HPLC method with refractometric detection for simultaneous
      determination of the three analytes in one analytical run has been developed for
      the first time. The samples containing TREO, S,S-EBDM, S,S-DEB and acetaminophen
      (internal standard) were directly injected onto the reversed phase column. To
      assure stability of the analytes and obtain their complete resolution, mobile
      phase composed of acetate buffer pH 4.5 and acetonitrile was applied. The linear
      range of the calibration curves of TREO, S,S-EBDM and S,S-DEB spanned
      concentrations of 20-6000, 34-8600 and 50-6000 MUM, respectively. Intra- and
      interday precision and accuracy of the developed method fulfilled analytical
      criteria. The stability of the analytes in experimental samples was also
      established. The validated HPLC method was successfully applied to the
      investigation of the kinetics of TREO activation to S,S-EBDM and S,S-DEB. At pH
      7.4 and 37  degrees C the transformation of TREO followed first-order kinetics
      with a half-life 1.5h.

PMID- 23146240
TI  - Application of Bio-Layer Interferometry for the analysis of protein/liposome
      interactions.
AB  - The development of biosensor technologies for the investigation of biomolecular
      interactions has markedly advanced over the last years. One promising biosensor
      platform, the Bio-Layer Interferometry (BLI), was developed by ForteBio with the
      main focus to qualify and quantify protein/protein interactions in research and
      routine applications. Here, a method to characterize protein/liposome binding
      interactions based on the biophysical principles of this platform is described.
      Three different liposome formulations and the protein hormone, recombinant human
      erythropoietin (rh-Epo) were used as models in the test system. Rh-Epo was
      immobilized on disposable optical fiber streptavidin (SA) biosensor tips and
      binding of different liposome formulations under certain conditions was measured.
      The assay performance was evaluated, followed by calculating the kinetic rate and
      affinity constants. The results showed that all liposome formulations formed
      extremely stable complexes with the immobilized protein. Nevertheless, liposome
      specific differences in binding affinities were determined. Furthermore, a
      liposome concentration dependent binding pattern was demonstrated. The
      combination of simple sample preparation, the opportunity of automation with high
      throughput in an acceptable time range and excellent reproducibility, makes this
      assay suitable for basic research as well as for drug discovery and drug
      screening to estimate drug/membrane interactions.

PMID- 23146241
TI  - Isolation and identification of a new sildenafil analogue adulterated in energy
      drink: propoxyphenyl sildenafil.
AB  - A new sildenafil analogue was found to be added illegally to a energy drink
      marketed for the enhancement of sexual function. The structure was determined as
      1-[4-propoxy-3-(6,7-dihydro-1-methyl-7-oxo-3-propyl-1H-pyrazolo[4,3-d]pyrimidin-5
      yl)phenylsulfonyl]-4-methylpiperazine. Owing to the inclusion of one more methyl
      group to sildenafil (on C-21), the detected compound was called "propoxyphenyl
      sildenafil". The sample was purified with column chromatography. The UV, IR,
      LC/MS (ESI) and completely assigned NMR data of propoxyphenyl sildenafil is
      reported. Having compared the structure with sildenafil, the results showed that
      the 2-ethoxy group (at the position on C-19) has been replaced by propoxy group.

PMID- 23146242
TI  - The synthesis and characterization of a nuclear membrane affinity chromatography
      column for the study of human breast cancer resistant protein (BCRP) using
      nuclear membranes obtained from the LN-229 cells.
AB  - BCRP expression has been reported in glioblastoma cell lines and clinical
      specimens and has been shown to be expressed both in purified nuclei and in the
      soluble cytoplasmic fraction. To date, the nuclear BCRP has not been
      characterized. Our laboratory has previously developed an online chromatographic
      approach for the study of binding interactions between ligands and protein,
      cellular membrane affinity chromatography. To this end, we have immobilized the
      nuclear membrane fragments onto an immobilized artificial membrane stationary
      phase (IAM), resulting in the nuclear membrane affinity chromatography (NMAC)
      column. Initial characterization was carried out on the radio flow detector, as
      well as the LC-MSD, using frontal displacement chromatography techniques.
      Etoposide, a substrate for BCRP, was initially tested, to determine the
      functional immobilization of BCRP. Frontal displacement experiments with multiple
      concentrations of etoposide were run and the binding affinity was determined to
      be 4.54 MUM, which is in close agreement with literature. The BCRP was fully
      characterized on the NMAC column and this demonstrates that for the first time
      the nuclear membranes have been successfully immobilized.

PMID- 23146243
TI  - Quantitative polymorph contaminant analysis in tablets using Raman and near infra
      red spectroscopies.
AB  - The detection and quantification of alternate polymorphs of active pharmaceutical
      ingredients (APIs), particularly at low concentrations is a key issue for the
      manufacture and analysis of solid-state formulations. Each polymorph can possess
      unique physical and chemical properties which in turn can directly affect factors
      such as solubility and bioavailability. Near infra-red (NIR) and Raman
      spectroscopies can be used for the rapid characterisation and quantification of
      polymorphs in solid samples. In this study we have generated a model tablet
      system with two excipients and a 10% API concentration, where the API is a
      mixture of the FII and FIII polymorphs of piracetam. Using transmission Raman
      spectroscopy (TRS) and NIR spectroscopy it was possible to detect FII polymorph
      contamination in these model tablets with limits of detection (LODs) of 0.6 and
      0.7%, respectively, with respect to the total tablet weight (or ~6-7% of the API
      content). The TRS method is the superior method because of the speed of analysis
      (~6s per sample), better sampling statistics, and because the sharper, more
      resolved bands in the Raman spectra allowed for easier interpretation of the
      spectral data. In addition the TRS used here provides facile access to the low
      frequency wavenumber region for analysis of solid-state lattice modes.

PMID- 23146244
TI  - Climate change and sustainable food production.
AB  - One of the greatest challenges we face in the twenty-first century is to
      sustainably feed nine to ten billion people by 2050 while at the same time
      reducing environmental impact (e.g. greenhouse gas (GHG) emissions, biodiversity
      loss, land use change and loss of ecosystem services). To this end, food security
      must be delivered. According to the United Nations definition, 'food security
      exists when all people, at all times, have physical and economic access to
      sufficient, safe and nutritious food to meet their dietary needs and food
      preferences for an active and healthy life'. At the same time as delivering food
      security, we must also reduce the environmental impact of food production. Future
      climate change will make an impact upon food production. On the other hand,
      agriculture contributes up to about 30% of the anthropogenic GHG emissions that
      drive climate change. The aim of this review is to outline some of the likely
      impacts of climate change on agriculture, the mitigation measures available
      within agriculture to reduce GHG emissions and outlines the very significant
      challenge of feeding nine to ten billion people sustainably under a future
      climate, with reduced emissions of GHG. Each challenge is in itself enormous,
      requiring solutions that co-deliver on all aspects. We conclude that the status
      quo is not an option, and tinkering with the current production systems is
      unlikely to deliver the food and ecosystems services we need in the future;
      radical changes in production and consumption are likely to be required over the
      coming decades.

PMID- 23146245
TI  - "Bouncing back": how Australia's leading women's magazines portray the postpartum
      'body'.

PMID- 23146246
TI  - The vasopressin V(1b) receptor antagonist SSR149415 in the treatment of major
      depressive and generalized anxiety disorders: results from 4 randomized, double
      blind, placebo-controlled studies.
AB  - OBJECTIVE: These studies were designed to evaluate the efficacy and tolerability
      of the first nonpeptide vasopressin V(1b) receptor antagonist, SSR149415, in the
      treatment of major depressive disorder (MDD) and generalized anxiety disorder
      (GAD). METHOD: Studies were randomized 8-week, double-blind, placebo-controlled
      trials evaluating 100- and 250-mg twice daily doses of SSR149415, placebo, and
      escitalopram 10 mg/day or paroxetine 20 mg/day, conducted from August 2006
      through February 2008. Participants met the Diagnostic and Statistical Manual of
      Mental Disorders, Fourth Edition, Text Revision criteria for MDD or GAD. Baseline
      Montgomery-Asberg Depression Rating Scale (MADRS) and Hamilton Depression Rating
      Scale (HDRS) total scores were >= 24 and 18, respectively, and in the GAD trial
      baseline Hamilton Anxiety Rating Scale (HARS) score was >= 22. Primary efficacy
      variables included changes from baseline in total score on HDRS or HARS and
      MADRS, and the secondary variable included changes in the Clinical Global
      Impressions-Severity of Illness score (CGI-S). A 4-week, double-blind, placebo
      controlled study evaluating the effect of 100- and 250-mg twice daily doses of
      SSR149415 on the hypothalamic-pituitary-adrenal (HPA) axis in MDD patients was
      also conducted. RESULTS: In the GAD trial, SSR149415 did not separate from
      placebo on the primary (HARS-100 mg: P = .29; 250 mg: P = .21) and secondary (CGI
      S-100 mg: P = .18; 250 mg: P = .24) outcome measures, while paroxetine
      demonstrated efficacy (HARS: P = .003; CGI-S: P = .01). In 2 MDD trials,
      SSR149415-treated patients did not show significant improvement from baseline on
      any outcome measure compared with placebo-treated patients (HDRS-100 mg: P = .21
      and .48, respectively; 250 mg: P = .22 and P = .46, respectively; CGI-S-100 mg: P
      = .64 and P = .82, respectively; 250 mg: P = .33 and P = .08, respectively). In
      the third MDD study, SSR149415 250 mg (P = .04), but not escitalopram (P = .15),
      demonstrated significant improvement compared to placebo on the HDRS total score
      at week 8. SSR149415 had no deleterious effects on the HPA axis. CONCLUSIONS:
      These studies demonstrate that SSR149415 may not be useful for the treatment of
      GAD and that its antidepressant potential needs to be further evaluated. TRIAL
      REGISTRATION: ClinicalTrials.gov identifiers: NCT00374166 (Sanofi ID number:
      DFI5880), NCT00361491 (Sanofi ID number: DFI5879), NCT00358631 (Sanofi ID number:
      DFI5878), NCT01606384 (Sanofi ID number: PDY5467).

PMID- 23146247
TI  - General emotion processing in social anxiety disorder: neural issues of cognitive
      control.
AB  - Anxiety disorders are characterized by deficient emotion regulation prior to and
      in anxiety-evoking situations. Patients with social anxiety disorder (SAD) have
      increased brain activation also during the anticipation and perception of non
      specific emotional stimuli pointing to biased general emotion processing. In the
      current study we addressed the neural correlates of emotion regulation by
      cognitive control during the anticipation and perception of non-specific
      emotional stimuli in patients with SAD. Thirty-two patients with SAD underwent
      functional magnetic resonance imaging during the announced anticipation and
      perception of emotional stimuli. Half of them were trained and instructed to
      apply reality-checking as a control strategy, the others anticipated and
      perceived the stimuli. Reality checking significantly (p<0.01) reduced activity
      in insular, amygdalar and medial thalamic areas during the anticipation and
      perception of negative emotional stimuli. The medial prefrontal cortex was
      comparably active in both groups (p>0.50). The results suggest that cognitive
      control in patients with SAD influences emotion processing structures, supporting
      the usefulness of emotion regulation training in the psychotherapy of SAD. In
      contrast to studies in healthy subjects, cognitive control was not associated
      with increased activation of prefrontal regions in SAD. This points to possibly
      disturbed general emotion regulating circuits in SAD.

PMID- 23146248
TI  - White matter microstructural abnormalities in patients with late-onset
      schizophrenia identified by a voxel-based diffusion tensor imaging.
AB  - Reduced fractional anisotropy (FA) has been previously found in diffusion tensor
      imaging (DTI) studies of white matter in schizophrenic patients. However, there
      are no reports in the literature that address FA alterations in late-onset
      schizophrenia (LOS). The current study measured FA in whole white matter and
      subsequently analyzed its association with psychotic symptoms in LOS. DTI was
      carried out in 20 patients with LOS and 17 age-, gender- and education-matched
      healthy subjects. Fractional anisotropy in different areas of white matter was
      compared between groups using a voxelwise analysis after inter-subject
      registration to standard Montreal Neurological Institute (MNI) space. Psychotic
      symptoms were assessed using the Positive and Negative Syndrome Scale (PANSS).
      Cognitive functions were measured using the Wisconsin Card Sorting Test (WCST),
      the Digit Span Test, and the Trail-making Test. Significant reduction in FA was
      found in the left parietal lobe and right posterior cingulum in LOS patients
      compared with healthy subjects. Significant deficits in cognitive functions were
      observed in LOS. No significant correlation was found between FA value and PANSS
      scores, cognitive test scores, age, or antipsychotic medication dosages in LOS
      patients. Our study suggests that abnormalities in white matter integrity may
      contribute to the pathophysiology of LOS. However, these microstructural
      abnormalities provided no evidence for the emergence of psychotic symptoms in
      LOS.

PMID- 23146249
TI  - Salience network-midbrain dysconnectivity and blunted reward signals in
      schizophrenia.
AB  - Theories of schizophrenia propose that abnormal functioning of the neural reward
      system is linked to negative and psychotic symptoms, by disruption of reward
      processing and promotion of context-independent false associations. Recently, it
      has been argued that an insula-anterior cingulate cortex (ACC) salience network
      system enables switching of brain states from the default mode to a task-related
      activity mode. Abnormal interaction between the insula-ACC system and reward
      processing regions may help explain abnormal reinforcer processing and symptoms.
      Here we use functional magnetic resonance imaging to assess the neural correlates
      of reward processing in schizophrenia. Furthermore, we investigated functional
      connectivity between the dopaminergic midbrain, a key region for the processing
      of reinforcers, and other brain regions. In response to rewards, controls
      activated task related regions (striatum, amygdala/hippocampus and midbrain) and
      the insula-ACC salience network. Patients similarly activated the insula-ACC
      salience network system but failed to activate task related regions. Reduced
      functional connectivity between the midbrain and the insula was found in
      schizophrenia, with the extent of this abnormality correlating with increased
      psychotic symptoms. The findings support the notion that reward processing is
      abnormal in schizophrenia and highlight the potential role of abnormal
      interactions between the insula-ACC salience network and reward regions.

PMID- 23146251
TI  - Structural brain features of borderline personality and bipolar disorders.
AB  - A potential overlap between bipolar disorder (BD) and borderline personality
      disorder (BPD) has been recently proposed. We aimed to assess similarities and
      differences of brain structural features in BD and BPD. Structural magnetic
      resonance imaging (MRI) was performed in 26 inpatients with BPD, 14 with BD, and
      40 age-and sex-matched healthycontrols (HC). Voxel-based morphometry analysis
      with Statistical Parametric Mapping (SPM) was used to localize and quantify gray
      (GM) and white matter (WM) abnormalities in BD and BPD compared to HC and to
      identify those specifically affected in each patient group. Region of interest
      (ROI)-based analyses were also performed for confirmation. GM density changes in
      BD are significantly more diffuse and severe than in BPD, as demonstrated in both
      SPM- and ROI-based analyses. The topography of GM alterations showed some regions
      of overlap, but each disorder had specific regions of abnormality (involving both
      cortical and subcortical structures in BD, confined mainly to fronto-limbic
      regions in BPD). WM density changes were less pronounced in both conditions and
      involved completely different regions. Although BPD and BD show a considerable
      overlap of GM changes, the topography of alterations is more consistent with the
      separate conditions hypothesis and with the vulnerability of separate neural
      systems. 

PMID- 23146250
TI  - Differences in subcortical structures in young adolescents at familial risk for
      schizophrenia: a preliminary study.
AB  - Schizophrenia has been associated with reduced volumes of subcortical structures
      on magnetic resonance imaging (MRI), but the relation of these reductions to
      familial risk for the disorder is unclear. We investigated the effect of familial
      risk for schizophrenia on regional subcortical volumes during adolescence, a
      period marked by steep maturational changes in brain structure and the emergence
      of psychotic symptoms. A group of 26 non-help-seeking, first-degree relatives of
      patients with schizophrenia and 43 matched healthy comparisons, between 9 and 18
      years of age, underwent MRI scanning and were rated for the presence of prodromal
      symptoms. Five subcortical regions-of-interest were tested for group differences
      and group by age interactions, as well as correlations with low-level prodromal
      symptoms in the familial risk group. Relative to comparisons, familial risk
      subjects demonstrated greater positive volume-age relationships in hippocampus,
      putamen, and globus pallidus. These results suggest that relatives of individuals
      with schizophrenia exhibit structural abnormalities in the subcortex as early as
      pre-adolescence, which may reflect altered neurodevelopment of these regions.

PMID- 23146252
TI  - Smoker-nonsmoker differences in neural response to smoking-related and affective
      cues: an fMRI investigation.
AB  - Smoking may sensitize brain systems to smoking cues while desensitizing systems
      to naturalistic rewards. This study examined smoker-nonsmoker differences in
      functional magnetic resonance imaging (fMRI) blood oxygen level dependent (BOLD)
      response to smoking-related and emotional images. Smokers, relative to
      nonsmokers, exhibited greater reactivity to smoking and decreased reactivity to
      emotional cues in the left middle frontal gyrus.

PMID- 23146253
TI  - Gray matter volume in major depressive disorder: a meta-analysis of voxel-based
      morphometry studies.
AB  - We designed this study to perform a meta-analysis of gray matter (GM) findings in
      major depressive disorder (MDD) by using the signed differential mapping (SDM)
      toolbox. The Pubmed, ScienceDirect and Scopus databases were searched, and only
      studies published or published online before November 2010 have been included.
      Twenty voxel-based morphometry (VBM) studies of adult MDD patients were entered
      in the meta-analysis by SDM toolbox with threshold criteria set as error
      probability less than 0.00005 and cluster more than 50 voxels. Onset age, numbers
      of patients and controls, gender ratio of both groups, ratio of medicated
      patients, depression rating scores, illness duration, co-morbidity and existence
      of corrected p value were also meta-regressed as covariates to exclude
      confounding biases. Voxel-wise meta-analytic results of these 20 VBM studies in
      MDD patients revealed that GM deficits were observed in the right anterior
      cingulate cortex and left anterior cingulate cortex when patients were compared
      with controls. The findings remained mostly unchanged in jackknife sensitivity
      analyses. The potential confounding factors had little impact on the results.
      This meta-analysis suggested GM deficits of the anterior cingulate cortex might
      be important in the etiology of MDD.

PMID- 23146255
TI  - Distal forearm fractures and inheritance of bone mass.

PMID- 23146256
TI  - Research in magnetic resonance.

PMID- 23146254
TI  - Atomoxetine increases fronto-parietal functional MRI activation in attention
      deficit/hyperactivity disorder: a pilot study.
AB  - We hypothesized that atomoxetine (ATMX) would produce similar brain effects in
      attention-deficit/hyperactivity disorder (ADHD) as those of methylphenidate
      (MPH). Eleven ADHD adults performed the Multi-Source Interference Task (MSIT)
      during functional magnetic resonance imaging (fMRI) at baseline and after 6 weeks
      of ATMX treatment. ATMX was associated with increased fMRI activation of
      dorsolateral prefrontal cortex, parietal cortex and cerebellum but not dorsal
      anterior midcingulate cortex (daMCC). These results suggest that ATMX and MPH
      have similar but not identical brain effects.

PMID- 23146257
TI  - Dynamic Nuclear Polarization and other magnetic ideas at EPFL.
AB  - Although nuclear magnetic resonance (NMR) can provide a wealth of information, it
      often suffers from a lack of sensitivity. Dynamic Nuclear Polarization (DNP)
      provides a way to increase the polarization and hence the signal intensities in
      NMR spectra by transferring the favourable electron  spin polarization of
      paramagnetic centres to the surrounding nuclear spins through appropriate
      microwave irradiation. In our group at EPFL, two complementary DNP techniques are
      under investigation: the combination of DNP with magic angle spinning at
      temperatures near 100 K ('MAS-DNP'), and  the combination of DNP at 1.2 K with
      rapid heating followed by the transfer of the sample to a high-resolution magnet
      ('dissolution DNP'). Recent applications of MAS-DNP to surfaces, as well as new
      developments of magnetization transfer of (1)H to (13)C at 1.2 K prior to 
      dissolution will illustrate the work performed in our group. A second part of the
      paper will give an overview of some 'non-enhanced' activities of our laboratory
      in liquid- and solid-state NMR.

PMID- 23146258
TI  - NMR spectroscopy: an excellent tool to understand RNA and carbohydrate
      recognition by proteins.
AB  - Structural biology plays a key role in understanding how networks of protein
      interactions with their partners are organized at the atomic level. In this
      review, we show that NMR is a very efficient method to solve 3D structures of
      protein - RNA and protein-carbohydrate complexes  of high quality. We explain the
      importance of studying such interactions and describe the main steps that are
      required to determine structures of these types of complexes by NMR. Finally, we
      show that X-ray crystallography and NMR are complementary methods and briefly
      report on advantages  and disadvantages of each approach.

PMID- 23146259
TI  - Exploring high-resolution magic angle spinning (HR-MAS) NMR spectroscopy for
      metabonomic analysis of apples.
AB  - Classical liquid-state high-resolution (HR) NMR spectroscopy has proved a
      powerful tool in the metabonomic analysis of liquid food samples like fruit
      juices. In this paper the application of (1)H high-resolution magic angle
      spinning (HR-MAS) NMR spectroscopy to apple tissue  is presented probing its
      potential for metabonomic studies. The (1)H HR-MAS NMR spectra are discussed in
      terms of the chemical composition of apple tissue and compared to liquid-state
      NMR spectra of apple juice. Differences indicate that specific metabolic changes
      are induced by juice  preparation. The feasibility of HR-MAS NMR-based
      multivariate analysis is demonstrated by a study distinguishing three different
      apple cultivars by principal component analysis (PCA). Preliminary results are
      shown from subsequent studies comparing three different cultivation methods by
      means  of PCA and partial least squares discriminant analysis (PLS-DA) of the HR
      MAS NMR data. The compounds responsible for discriminating organically grown
      apples are discussed. Finally, an outlook of our ongoing work is given including
      a longitudinal study on apples.

PMID- 23146260
TI  - Solid-state NMR: an eye opener in surface chemistry.
AB  - Solid-state NMR plays a critical role in establishing the atomic structure of
      surface species, obtained by the controlled grafting of organometallic complexes
      onto amorphous oxide supports, a promising strategy towards molecularly defined
      heterogeneous catalysts. Using one-dimensional  or multi-dimensional NMR analysis
      allows us to map the structure of organometallic residues on surfaces, in a
      similar fashion that the structure of homogeneous catalysts can be determined
      using solution NMR techniques. In addition, chemical shift anisotropy analysis
      can be used as a tool to  obtain detail structures and to determine the dynamics
      of surface species. In combination with DFT calculations we have also shown that
      the structure of aluminum species can be determined using high-field and
      ultrafast (27)Al NMR. Finally, we discussed the latest development in Dynamic 
      Nuclear Polarization, which allows the selective enhancements of the NMR signals
      of surface species, thus reducing the NMR acquisition time by factors up to
      10,000. This makes solid-state NMR an indispensible tool in determining structure
      property relationship and in the development of advanced  materials including
      catalysts through more rational approach.

PMID- 23146261
TI  - Solution NMR studies of membrane-protein-chaperone complexes.
AB  - The biosynthesis of the bacterial outer membrane depends on molecular chaperones
      that protect hydrophobic membrane proteins against aggregation while transporting
      them across the periplasm. In our ongoing research, we use high-resolution NMR
      spectroscopy in aqueous solution as the main  technique to characterize the
      structures and biological functions of these membrane-protein-chaperone
      complexes. Here, we describe NMR studies addressing three functional aspects of
      periplasmic membrane-protein-chaperone complexes. Firstly, the Escherichia coli
      outer membrane  protein OmpX binds to each of the two chaperones, Skp and SurA,
      in structurally at least partially similar states despite fundamental differences
      between the three-dimensional structures of the chaperones. Secondly, we show
      that the Skp-bound state of OmpX is equivalent to a chemically denatured  state
      in terms of its refolding competence into detergent micelles in vitro. Thirdly,
      we use amino acid mutation analysis to show that the interaction of OmpX to Skp
      is not dominated by the two most hydrophobic segments of OmpX.

PMID- 23146262
TI  - Combination of homonuclear decoupling and spectral aliasing to increase the
      resolution in the (1)H dimension of 2D NMR experiments.
AB  - Broadband homonuclear decoupling (BBHD) in the indirect (1)H dimension of 2D
      experiments can be obtained using a modified Zangger and Sterk combination of a
      selective pulse with a pulsed-field gradient. The coupling structure of signals
      is reduced to a singlet along the F1  dimension at the cost of a sensitivity
      loss. With the classical sampling in F1, the full resolving power of BBHD
      experiments requires very long acquisition times. Spectral aliasing can reduce
      the number of time increments accessing the top resolution of homodecoupled
      spectra of small molecules  by two orders of magnitude. The TOCSY spectra of
      androst-4-ene-3,17-dione are shown as an example.

PMID- 23146263
TI  - Automated projection spectroscopy (APSY) for the assignment of NMR resonances of
      biological macromolecules.
AB  - High resolution nuclear magnetic resonance (NMR) spectroscopy in solution is an
      established technique in structural biology. Detailed functional and structural
      studies of biological macromolecules by NMR require the assignment of the
      chemical shifts to specific nuclei. In biological  applications, the necessary
      data is usually obtained from a number of two- and three-dimensional (2D and 3D)
      NMR experiments. Often, these data cannot be fully analyzed by automated computer
      programs due to insufficient separation and resolution of the signals in the
      available spectra. Then,  complete resonance assignment requires manual
      interaction and can become a long and labor-intensive task. Automated projection
      spectroscopy (APSY) allows the substantial improvement of the resolution by
      providing spectral information from four and higher dimensional experiments
      without measuring  the full spectrum, which would by far exceed any acceptable
      measuring time. APSY only measures a series of projections of the high
      dimensional spectrum which can be obtained in a much shorter time. Peak picking
      of the projection spectra provides the basis for the calculation of the high
      dimensional  chemical shift correlation space by the algorithm GAPRO. The
      resulting high-dimensional peak lists are commonly artifact-free and of
      exceptional precision. Along with their high number of correlated nuclei they
      provide an ideal basis for reliable automated assignment. We will introduce the 
      basic concepts of APSY, illustrate them with an application of a 6D APSY-seq
      HNCOCANH experiment, and discuss some practical aspects.

PMID- 23146264
TI  - Insights into the mechanism of action and cellular targets of ruthenium complexes
      from NMR spectroscopy.
AB  - NMR spectroscopy has proved extremely beneficial in the investigation of
      inorganic drugs from the time that cisplatin was first introduced into the clinic
      more than 30 years ago. Both (195)Pt and (15)N NMR were used in early studies and
      made a major contribution in  the understanding of the molecular mechanism of
      action from model studies involving reactions with amino acids and nucleotides.
      Over the past decade, ruthenium drugs have proved to be a valuable alternative to
      platinum drugs, and NMR has also provided unique insights into their molecular
      mechanism  of action including investigations of simple aquation reactions,
      protein binding and the kinetics and sequence selectivity of DNA binding
      interactions. In this article, emphasis is given to define the cellular targets
      and elucidate some of the mechanistic profiles of recent ruthenium-based 
      organometallic compounds offering efficacy toward cancer cells, by various NMR
      techniques.

PMID- 23146265
TI  - Approaches towards structures of Y receptors, examples of human G-protein coupled
      receptors, by solution NMR.
AB  - Despite recent advances no solution structure for a true G-protein coupled
      receptor (GPCR) is available today due to biochemical and spectroscopic problems.
      Herein we review our attempts to obtain assignments of GPCRs based on fragments
      comprising 2-3 transmembrane helices. The fragments  are expressed in a
      heterologous system, and studied in detergent micelles using solution NMR
      spectroscopy. We report on the status of assignments of fragments from the Y4
      receptor, a human GPCR. Assignments for the majority of the backbone resonances
      are available as well as sidechain assignments  for the first two TM helices.
      Residues of TM4 are largely invisible. We review technical issues in preparing
      these samples and in the data analysis. In addition we developed an approach in
      which we have grafted the extracellular loops of the Y1 receptor onto a beta
      barrel scaffold derived  from the E. coli outer membrane protein OmpA. We could
      demonstrate that all loops can be successfully transferred, and that the
      resulting protein can be successfully refolded. The system is capable of
      recognizing the ligands from the neuropeptide Y family.

PMID- 23146266
TI  - Discrete three-dimensional representation of macromolecular motion from eNOE
      based ensemble calculation.
AB  - Three-dimensional structural data and description of dynamics are fundamental to
      infer and understand protein function. Structure determination by NMR follows
      well-established protocols while NMR relaxation phenomena provide insights into
      local molecular dynamics. However, methods to  detect concerted motion were not
      pursued until very recently. Here, we present an ensemble-based structure
      determination protocol using ensemble-averaged distance restraints obtained from
      exact NOE (eNOE) rate constants. An application of our protocol to the model
      protein GB3 established an  ensemble of structures that reveals correlated motion
      across the beta-sheet and concerted motion between the backbone and side chains
      localized in the core. Furthermore, the data repudiate concerted conformational
      exchange between the beta-sheet and the alpha-helix.

PMID- 23146267
TI  - NMR spectroscopy in bioinorganic chemistry.
AB  - Multinuclear and multidimensional nuclear magnetic resonance (NMR) spectroscopy
      is applied in our groups to gain insights into the role of metal ions for the
      function and structure of large biomolecules. Specifically, NMR is used i) to
      investigate how metal ions bind to nucleic acids  and thereby control the folding
      and structure of RNAs, ii) to characterize how metal ions are able to stabilize
      modified nucleic acids to be used as potential nanowires, and iii) to
      characterize the formation, structure, and role of the diverse metal clusters
      within plant metallothioneins.  In this review we summarize the various NMR
      experiments applied and the information obtained, demonstrating the important and
      fascinating part NMR spectroscopy plays in the field of bioinorganic chemistry.

PMID- 23146268
TI  - Biological solid-state NMR at ETH Zurich.
AB  - Solid-state Magnetic Resonance has been greatly developed over the past decade.
      Higher field spectrometers and other technical developments are expected to lead
      to further significant improvements.

PMID- 23146271
TI  - Construction of a peptide microarray for auto-anti- body detection.
AB  - Peptide and protein microarrays provide a multiplex approach to identification
      and quantification of protein-protein interactions (PPI), useful to study for
      instance antigen-antibody properties. Multivariate serology assays detecting
      multiple tumor auto-antibodies (TAA)  is an emerging class of blood tests for
      cancer detection. Here we describe the efficient coupling of peptide baits
      derived from the BRCA1-associated RING domain protein 1 (BARD1) to a solid
      surface and detection of a commercially available anti-BARD1 antibody with this
      newly designed peptide  microarray. Analytical sensitivity and specificity were
      shown to be comparable to a microtiter plate based enzyme-linked immunosorbent
      assay (ELISA).

PMID- 23146273
TI  - Nucleolin mediates the antiangiogenesis effect of the pseudopeptide N6L.
AB  - BACKGROUND: Nucleolin is a protein over-expressed on the surface of activated
      cells. Recent studies have underlined the involvement of cell surface nucleolin
      in angiogenesis processes. This cell surface molecule serves as a receptor for
      various ligands implicated in pathophysiological processes such as growth
      factors, cell adhesion molecules like integrins, selectins or laminin-1,
      lipoproteins and viruses. N6L is a synthetic multimeric pseudopeptide that binds
      cell surface expressed nucleolin and inhibits cell proliferation. RESULTS: In the
      present work, we further investigated the mechanisms of action of pseudopeptide
      N6L on angiogenesis using HUVECs. We provide evidence that N6L inhibits the in
      vitro adhesion, proliferation and migration of HUVECs without inducing their
      apoptosis. In addition, we found that N6L downregulates MMP-2 in HUVECs. The
      above biological actions are regulated by SRC, ERK1/2, AKT and FAK kinases as we
      found that N6L inhibits their activation in HUVECs. Finally, down regulation of
      nucleolin using siRNA demonstrated the implication of nucleolin in the biological
      actions of these peptides. CONCLUSIONS: Taken together, these results indicate
      that N6L could constitute an interesting therapeutic tool for treating diseases
      associated with excessive angiogenesis.

PMID- 23146274
TI  - Mobilization of arsenic in aquifers from the Datong Basin, China: evidence from
      geochemical and iron isotopic data.
AB  - Iron isotope compositions of various Fe pools in aquifer sediments were measured
      at a known As-contaminated site in the Datong Basin, China. The delta(56)Fe
      values of HCl-extracted poor-crystalline Fe(III) range widely from -0.410/00 to
      0.360/00. We interpret the low Fe(II)/Fe(Extractable) ratios (<50%) and the
      negative correlation between Fe(II)/Fe(Extractable) and delta(56)Fe values in HCl
      extracted poor-crystalline Fe to be best explained by redox cycling of Fe induced
      by microbial Fe(III) reduction. However, the high Fe(II)/Fe(Extractable) ratios
      (~/>70%) and positive correlation between Fe(II)/Fe(Extractable) and delta(56)Fe
      values for HCl-extracted poor-crystalline Fe indicates production of sulfides
      (FeSs). The delta(56)Fe values of crystalline Fe(III) extracted by reductant
      appears to be comparatively small varying from -0.010/00 to 0.240/00, which is
      consistent with the delta(56)Fe values for ferric oxides/hydroxides having
      undergone microbial Fe(III) reduction. The Fe isotope composition of various Fe
      pools shows the transformation between crystalline Fe(III) and poor-crystalline
      crystalline Fe(III) and the secondary Fe(II) phases has already occurred or is
      occurring in aquifer sediments. More importantly, there is a significant
      difference in the As concentrations in crystalline Fe(III) oxides/hydroxides and
      HCl-extracted Fe phases. The concentrations of As range from 1.6 to 29.9 mg kg(
      1) and from 0.6 to 3.0 mg kg(-1), for crystalline Fe(III) and HCl-extracted Fe
      phases respectively. Accordingly, the transformation of Fe minerals induced by
      microbial Fe(III) reduction can contribute to the mobilization of As. This study
      is the first to examine the Fe isotope compositions in high As aquifer sediments;
      the results show that the Fe isotope would be an important tool in demonstrating
      the enrichment of As in groundwater.

PMID- 23146275
TI  - Preliminary data suggest that venlafaxine environmental concentrations could be
      toxic to plants.
AB  - Venlafaxine hydrochloride is a structurally novel antidepressant. Its occurrence
      in surface waters and drinking water has only been reported in recent works. The
      aim of this work is to assess the acute and chronic sublethal toxicity of
      venlafaxine in relevant taxa of riparian ecosystems. We used the fern Polystichum
      setiferum during the critical life stage of development. Reliable biomarkers of
      cell viability (mitochondrial activity), plant physiology (chlorophyll), and
      growth (DNA content) were assessed as sensitive endpoints of toxicity. About DNA
      quantification, our results show that venlafaxine induces acute lethal
      phytotoxicity at 24 and 48 h (LOECs 1 MUg L(-1) and 0.1 MUg L(-1), respectively).
      At 24 h, hormetic effects in spores of P. setiferum mitochondrial activity mask
      lethality and adverse effects are observed (LOEC 1 MUg L(-1)). At 48 h a
      reduction in the mitochondrial activity happens (LOEC 10 MUg L(-1)). In chronic
      exposure of 1 week, LOEC for DNA is 0.1 MUg L(-1). Mitochondrial activity showed
      a strong hormetic stimulation of a surviving spore population (LOEC 10 MUg L(
      1)). Changes were not observed in chlorophyll autofluorescence. Environmental
      concentrations of venlafaxine can be deleterious for the development of
      significant populations of sensitive individuals in riparian ecosystems.

PMID- 23146276
TI  - In vitro biotransformation of PBDEs by root crude enzyme extracts: potential role
      of nitrate reductase (NaR) and glutathione S-transferase (GST) in their
      debromination.
AB  - In order to investigate the enzyme transformation of PBDEs and to track the key
      enzymes involved in PBDE degradation in plants, in vivo exposure of plants of
      ryegrass, pumpkin and maize and in vitro exposure of their root crude enzyme
      extracts to PBDEs were conducted. Degradation of PBDEs in the root crude enzyme
      solutions fit well with the first order kinetics (R(2)=0.52-0.97, P<0.05), and
      higher PBDEs degraded faster than the lower ones. PBDEs could be transformed to
      lower brominated PBDEs and hydroxylated-PBDEs by the root crude enzyme extracts
      with debromination as the main pathway which contributed over 90% of PBDE
      depletion. In vitro and in vivo exposure to PBDEs produced similar responses in
      root enzyme activities of which the nitroreductase (NaR) and glutathione
      transferase (GST) activities decreased significantly, while the peroxidase,
      catalase and cytochrome P-450 activities had no significant changes. Furthermore,
      higher enzyme concentrations of NaR and GST led to higher PBDE debromination
      rates, and the time-dependent activities of NaR and GST in the root crude enzyme
      extracts were similar to the trends of PBDE depletion. All these results suggest
      that NaR and GST were the key enzymes responsible for PBDE degradation. This
      conclusion was further confirmed by the in vitro debromination of PBDEs with the
      commercial pure NaR and GST.

PMID- 23146277
TI  - What are the benefits of a short therapeutic conversation intervention with acute
      psychiatric patients and their families? A controlled before and after study.
AB  - BACKGROUND: Psychiatric illness of a family member can have a serious impact on
      the entire family. In addition, these families are faced with psychological
      burdens and stigmas. Little is known about the effectiveness of family nursing
      interventions on patients and their families when a family member is admitted for
      psychiatric treatment. Few studies have been published where family nursing
      interventions are integrated into routine inpatient services. PURPOSE: To
      evaluate the effectiveness of implementing a therapeutic conversation
      intervention in acute inpatient psychiatry with families, by evaluating family
      perceived support, expressive family function and general well-being. DESIGN AND
      METHODS: A controlled before and after study design was used. Patients and family
      members at four acute psychiatric units at a university hospital were selected
      for the implementation of family systems nursing (FSN). The nurses on one acute
      psychiatric unit were educated, trained, and supervised in a therapeutic
      conversation intervention built on the Calgary Family Assessment and
      Interventions models (Wright and Leahey, 2009). In the intervention group, 68
      patients and 68 family members (N=136), received two-to-five therapeutic
      conversations with a nurse. The control groups were from three other acute units
      at the hospital, where 74 patients and 74 family members (N=148) received family
      nursing care as usual. RESULTS: The main findings indicated that family members
      who received the short therapeutic conversation intervention were found to
      perceive significant higher cognitive and emotional support from the nurses than
      family members who received standard care. CONCLUSION: The benefits of a specific
      short-term therapeutic conversation intervention are evident and valuable for
      nurses working in acute psychiatry. These positive results for families of
      psychiatric patients should not only encourage and propel clinical educators,
      clinical nurses and nurse researchers and other health professionals to develop
      and implement the therapeutic conversation intervention in acute psychiatric
      services but also be part of ritualized protocols of practice.

PMID- 23146278
TI  - Heavy smoking before coronary surgical procedures affects the native matrix
      metalloproteinase-2 and matrix metalloproteinase-9 gene expression in saphenous
      vein conduits.
AB  - BACKGROUND: Smoking has numerous effects that may promote atherosclerosis, but
      the pathogenesis of smoking-related vein graft disease after coronary artery
      bypass grafting (CABG) remains incompletely understood. Matrix metalloproteinase
      (MMP) subtypes MMP-2 and MMP-9 have been identified as the key components in
      vascular remodeling processes. However little is known about the native MMP2 and
      MMP9 gene expression in saphenous vein (SV) conduits of heavy smokers undergoing
      CABG. METHODS: Two hundred eight patients were divided into 6 groups: nonsmokers,
      heavy smokers, 3-month quitters, 6-month quitters, 12-month quitters, and long
      term quitters. mRNA and protein levels of MMP-2, MMP-9, and tissue inhibitors of
      metalloproteinases (TIMPs) 1 and TIMP-2 were analyzed. In a clinical study, SV
      graft patency after surgical procedures was followed up. RESULTS: Compared with
      the nonsmoker group, MMP2 and MMP9 gene expression was significantly increased in
      the other 5 groups (p < 0.05). In contrast to MMP response, TIMP1 and TIMP2 gene
      expression was significantly decreased (p < 0.05). An association of increased
      MMP2 and MMP9 gene expression with poor SV graft patency could be found in the
      clinical data from follow-up. CONCLUSIONS: Heavy smoking noticeably increases
      native MMP2 and MMP9 gene expression in the SV before CABG. Even after long-term
      cessation of smoking, the dysregulated MMP2 and MMP9 gene expression cannot
      recover to normal levels. With the elevated native MMP2 and MMP9 gene expression
      in the SV induced by heavy smoking, more vein graft disease can be found on long
      term follow-up.

PMID- 23146279
TI  - Optimized local infarct restraint improves left ventricular function and limits
      remodeling.
AB  - BACKGROUND: Preventing expansion and dyskinetic movement of a myocardial
      infarction (MI) can limit left ventricular (LV) remodeling. Using a device
      designed to produce variable alteration of infarct stiffness and geometry, we
      sought to understand how these parameters affect LV function and remodeling early
      after MI. METHODS: Ten pigs had posterolateral infarctions. An unexpanded device
      was placed in 5 animals at the time of infarction and 5 animals served as
      untreated controls. One week after MI animals underwent magnetic resonance
      imaging to assess LV size and regional function. In the treatment group, after
      initial imaging, the device was expanded with 2, 4, 6, 8, and 10 mL of saline.
      The optimal degree of inflation was defined as that which maximized stroke volume
      (SV). The device was left optimally inflated in the treatment animals for 3
      additional weeks. RESULTS: One week after MI, device inflation to 6 mL or greater
      significantly (p < 0.05) decreased end-systolic volume (0 mL, 59.9 mL +/- 3.8; 6
      mL, 54.0 mL +/- 3.1; 8 mL, 50.5 mL +/- 4.8; and 10 mL, 46.1 mL +/- 2.2) and
      increased ejection fraction (EF) (0 mL, 0.346 +/- 0.016; 6 mL, 0.0397 +/- 0.009;
      8 mL, 0.431 +/- 0.027; and 10 mL, 0.441 +/- 0.009). Systolic volume significantly
      (p < 0.05) improved for the 6 mL and 8 mL volumes (0 mL, 31.2 mL +/- 2.6; 6 mL,
      35.7 mL +/- 2.0; and 8 mL, 37.5 mL +/- 1.9) but trended downward for 10 mL (36.6
      mL +/- 2.8). At 4 weeks after MI, end-diastolic volume and end-systolic volume
      were unchanged from 1-week values in the treatment group while the control group
      continued to dilate. Systolic volume (38.2 +/- 4.4 mL vs 34.0.1 +/- 4.8 mL, p =
      0.08) and EF (0.360 +/- 0.026 vs 0.276 +/- 0.014, p = 0.04) were also better in
      the treatment animals. CONCLUSIONS: Optimized isolated infarct restraint can
      limit adverse LV remodeling after MI. The tested device affords the potential for
      a patient-specific therapy to preserve cardiac function after MI.

PMID- 23146281
TI  - Characterization of extensively drug-resistant Mycobacterium tuberculosis in
      Nepal.
AB  - The emergence of extensively drug-resistant tuberculosis (XDR-TB) has raised
      public health concern for global control of TB. Although molecular
      characterization of drug resistance-associated mutations in multidrug-resistant
      isolates in Nepal has been made, mutations in XDR isolates and their genotypes
      have not been reported previously. In this study, we identified and characterized
      13 XDR Mycobacterium tuberculosis isolates from clinical isolates in Nepal. The
      most prevalent mutations involved in rifampicin, isoniazid, ofloxacin, and
      kanamycin/capreomycin resistance were Ser531Leu in rpoB gene (92.3%), Ser315Thr
      in katG gene (92.3%), Asp94Gly in gyrA gene (53.9%) and A1400G in rrs gene
      (61.5%), respectively. Spoligotyping and multilocus sequence typing revealed that
      69% belonged to Beijing family, especially modern types. Further typing with 26
      loci variable number of tandem repeats suggested the current spread of XDR M.
      tuberculosis. Our result highlights the need to reinforce the TB policy in Nepal
      with regard to control and detection strategies.

PMID- 23146282
TI  - Analogue-based design, synthesis and docking of non-steroidal anti-inflammatory
      agents. Part 2: methyl sulfanyl/methyl sulfonyl substituted 2,3-diaryl-2,3
      dihydro-1H-quinazolin-4-ones.
AB  - A series of methyl sulfanyl/methyl sufonyl substituted 2,3-diaryl-2,3-dihydro-1H
      quinazolin-4-one were designed using analogue-based design, scaffold hopping and
      shape similarity matching. The designed compounds were synthesized in 2-3 steps
      with simple chemistry and screened by ovine cyclooxygenases (COXs) inhibitory
      assay and carrageenan-induced rat paw edema assay. Among the screened compounds,
      two compounds exhibited 100% cyclooxygenase-2 (COX-2) inhibitory potency without
      showing cycloxygenase-1 (COX-1) inhibition at 20 MUM. The compounds also showed
      promising in vivo anti-inflammatory potential. A structure-activity relationship
      within the dataset was established by correlating the effect of aromatic ring
      substituent constants, structural variables and physico-chemical descriptors with
      in vivo anti-inflammatory activity. Molecular docking studies were also performed
      on the title compounds to study the binding interactions to COX-2 active site
      residues. The experimentally determined COX-2 inhibitory activity was found
      moderately correlating with binding modes predicted for compounds by Glide XP
      dock scoring function. The 2,3-diaryl-2,3-dihydro-1H-quinazolin-4-one
      pharmacophore reported herein should be a new lead for further development of
      novel non-steroidal anti-inflammatory agents.

PMID- 23146280
TI  - The prognostic and predictive value of mRNA expression of vascular endothelial
      growth factor family members in breast cancer: a study in primary tumors of high
      risk early breast cancer patients participating in a randomized Hellenic
      Cooperative Oncology Group trial.
AB  - INTRODUCTION: The main prognostic variables in early breast cancer are tumor
      size, histological grade, estrogen receptor/progesterone receptor (ER/PgR)
      status, number of positive nodes and human epidermal growth factor receptor 2
      (HER2) status. The present study evaluated the prognostic and/or predictive value
      of vascular endothelial growth factor (VEGF) family members in high-risk early
      breast cancer patients treated with adjuvant chemo-hormonotherapy. METHODS: RNA
      was isolated from 308 formalin-fixed paraffin-embedded primary tumor samples from
      breast cancer patients enrolled in the HE10/97 trial, evaluating adjuvant dose
      dense sequential chemotherapy with epirubicin followed by cyclophosphamide,
      methotrexate, fluorouracil (CMF) with or without paclitaxel (E-T-CMF versus E
      CMF). A fully automated method based on magnetic beads was applied for RNA
      extraction, followed by one-step quantitative RT-PCR for mRNA analysis of VEGF-A,
      -B, -C and vascular endothelial growth factor receptor (VEGFR) 1, 2, 3. RESULTS:
      With a median follow-up of 8 years, 109 patients (35%) developed a relapse and 80
      patients (26%) died. In high VEGF-C and VEGFR1 mRNA expressing tumors, ER/PgR
      negative tumors (Fisher's exact test, P = 0.001 and P = 0.021, respectively) and
      HER2-positive tumors (P <0.001 and P = 0.028, respectively) were more frequent
      than in low VEGF-C and VEGFR1 expressing tumors, respectively. From the VEGF
      family members evaluated, high VEGFR1 mRNA expression (above the 75th percentile)
      emerged as a significant negative prognostic factor for overall survival (OS;
      hazard ratio (HR) = 1.60, 95% confidence interval (CI): 1.01 to 2.55, Wald's P =
      0.047) and disease-free survival (DFS; HR = 1.67, 95% CI: 1.13 to 2.48, P =
      0.010), when adjusting for treatment group. High VEGF-C mRNA expression was
      predictive for benefit from adjuvant treatment with paclitaxel (E-T-CMF arm) for
      OS (test for interaction, Wald's P = 0.038), while in multivariate analysis the
      interaction of VEGF-C with taxane treatment was significant for both OS (Wald's P
      = 0.019) and DFS (P = 0.041) and continuous VEGF-B mRNA expression values for OS
      (P = 0.019). CONCLUSIONS: The present study reports, for the first time, that
      VEGF-C mRNA overexpression, as assessed by qRT-PCR, has a strong predictive value
      in high-risk early breast cancer patients undergoing adjuvant paclitaxel
      containing treatment. Further studies are warranted to validate the prognostic
      and/or predictive value of VEGF-B, VEGF-C and VEGFR1 in patients treated with
      adjuvant therapies and to reveal which members of the VEGF family could possibly
      be useful markers in identifying patients who will benefit most from anti-VEGF
      strategies. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry
      (ANZCTR) ACTRN12611000506998.

PMID- 23146283
TI  - Geographical distribution and epidemiological features of Old World Leishmania
      infantum and Leishmania donovani foci, based on the isoenzyme analysis of 2277
      strains.
AB  - A series of 2277 Leishmania strains from Old World visceral leishmaniasis foci,
      isolated between 1973 and 2008, were studied by isoenzyme analysis. The strains
      were obtained from humans, domestic and wild carnivores, rodents and phlebotomine
      sandflies, and came from 36 countries. In all, 60 different zymodemes were
      identified and clustered by a phenetic analysis into 3 different groups
      corresponding to the typically visceralizing species L. donovani (20 zymodemes,
      169 strains), L. archibaldi (3 zymodemes, 46 strains) and L. infantum (37
      zymodemes, 2,062 strains). The taxonomic position of these isoenzymatic groups is
      discussed in view of contradictory results obtained from recent molecular
      studies.

PMID- 23146285
TI  - Bilateral total knee arthroplasty in a one-stage surgical procedure.
AB  - INTRODUCTION: Bilateral total knee arthroplasty (TKA) in a one-stage surgical
      procedure has the advantage of a single hospital stay, shorter rehabilitation,
      and reduced patient management costs. However, until now the use of this strategy
      has been limited by the fear of a higher rate of perioperative complications. The
      hypothesis of this study was that in selected patients, this management strategy
      would not result in any serious complications. MATERIALS AND METHODS: This
      prospective 24-month pilot study was performed in a continuous series of patients
      without a control group. Inclusion criteria were bilateral non-infectious
      gonarthropathy, in patients classified as American Society of Anesthesiology
      (ASA) 1 or 2 and presenting with a preoperative hemoglobin level of at least
      13g/dL. All patients underwent a pre- and postoperative evaluation using the
      International Knee Society (IKS) and Knee Injury and Osteoarthritis Score (KOOS)
      scores. RESULTS: Thirty patients were included in the study (25 women, mean age
      70.3years old [32 to 88years]; five ASA 1 and 25 ASA 2). All patients were
      followed-up and evaluated for a mean 18months (6 to 30months). Three deep vein
      thromboses, one cardiopulmonary accident and three confusional states were
      reported, but there were no perioperative deaths, pulmonary embolisms, nosocomial
      infections or revision procedures. At 18months follow-up the IKS score had
      improved from 98 (33-139) preoperatively to 169 (62-200) postoperatively. The
      five items of the KOOS score improved significantly. DISCUSSION: This preliminary
      series confirms that bilateral total knee replacement in a one-stage surgical
      procedure is a reliable alternative to a two-stage procedure in ASA 1 and 2
      patients. Because of the savings in health costs with this strategy, public
      healthcare authorities should provide support by creating and sponsoring a
      specific group for further study. LEVEL OF EVIDENCE: 4, prospective, no control
      group.

PMID- 23146284
TI  - Autism spectrum symptoms in children with neurological disorders.
AB  - BACKGROUND: The aims of the present study were to assess symptoms associated
      with an autism spectrum disorder (ASD) in children with neurological disorders as
      reported by parents and teachers on the Autism Spectrum Screening Questionnaire
      (ASSQ), as well as the level of agreement between informants for each child.
      METHODS: The ASSQ was completed by parents and teachers of the 5781 children (11
      13 years) who participated in the second wave of the Bergen Child Study (BCS), an
      on-going longitudinal population-based study. Out of these children, 496 were
      reported to have a chronic illness, including 99 whom had a neurological
      disorder. The neurological disorder group included children both with and without
      intellectual disabilities. RESULTS: Children with neurological disorders obtained
      significantly higher parent and teacher reported ASSQ scores than did non
      chronically ill children and those with other chronic illnesses (p<.01; ES = .50
      1.01), and 14.1% were screened above the positive cutoff score for ASD according
      to their combined parent and teacher ASSQ scores. Parent/teacher agreement over
      ASSQ scores for children with neurological disorders was moderate to high for the
      total score and for three sub scores generated from a factor analysis, and low to
      moderate for single items. CONCLUSIONS: The ASSQ identifies a high rate of ASD
      symptoms in children with neurological disorders, and a large number of children
      screened in the positive range for ASD. Although a firm conclusion awaits further
      clinical studies, the present results suggest that health care professionals
      should be aware of potential ASD related problems in children with neurological
      disorders, and should consider inclusion of the ASSQ or similar screening
      instruments as part of their routine assessment of this group of children.

PMID- 23146286
TI  - Influence of screw type on initial coronal and sagittal radiological correction
      with hybrid constructs in adolescent idiopathic scoliosis. Correction priorities.
AB  - BACKGROUND: Pedicle screw constructs for spinal instrumentation in patients with
      adolescent idiopathic scoliosis (AIS) are effective in providing coronal plane
      correction but can result in loss of kyphosis, which in turn can lead to loss of
      lordosis. Hybrid constructs have been found superior over pedicle screw
      constructs in terms of thoracic kyphosis restoration. In this study, our
      objective was to compare outcomes with monoaxial versus polyaxial screws in an
      AIS population treated with hybrid constructs. HYPOTHESIS: Monoaxial screws
      provide better correction in the coronal plane but result in loss of thoracic
      kyphosis, whereas thoracic kyphosis is preserved when polyaxial screws are used.
      MATERIAL AND METHODS: We retrospectively analysed data from 60 patients (mean
      age, 15years) with Lenke 1, 2, or 3 AIS treated using a hybrid construct with
      self-retaining bilaminar hook claws cranially, pedicle screws between the last
      instrumented vertebra and T11 caudally, and sublaminar universal clamps between
      the two extremities of the construct. Monoaxial screws were used in the first 30
      patients (MS group) and polyaxial screws in the next 30 patients (PS group).
      Student's t test was performed to compare the two groups in terms of thoracic
      Cobb angle correction and T4-T12 kyphosis 3 months after surgery. RESULTS: No
      significant preoperative differences were found between the two groups. At last
      follow-up, the residual Cobb angle was significantly greater in the PS group than
      in the MS group (20.3 degrees  versus 15 degrees ) with a percentage of
      correction of 72.1% in the MS group versus 64.8% in the PS group. In the sagittal
      plane, the thoracic kyphosis was significantly greater in the PS group than in
      the MS group (26.6 degrees  versus 23 degrees ). DISCUSSION: This preliminary
      study shows that, even within a population managed using hybrid constructs, which
      are associated with less iatrogenic hypokyphosis, differences exist according to
      the technique used. The importance of sagittal spinal balance has been abundantly
      documented in the literature, and sagittal malalignment, particularly due to
      iatrogenic factors, is associated with poorer clinical outcomes in adults with
      spinal deformities. Therefore, there is a critical need to determine whether the
      treatment priority is optimal correction in the coronal plane or in the sagittal
      plane. We believe that the main focus should be sagittal plane correction, even
      at the expense of a slight decrease in coronal plane correction. Long-term
      studies are needed to confirm our preliminary findings.

PMID- 23146287
TI  - Clinical outcome and quality of life in octogenarians following transcatheter
      aortic valve implantation (TAVI) for symptomatic aortic stenosis.
AB  - OBJECTIVE: TAVI is the alternative option in pts with AS deemed ineligible for
      surgery. Although mortality and morbidity are measures to assess the
      effectiveness of treatments, quality of life (QOL) should be an additional
      target. We assessed clinical outcome and QOL in octogenarians following TAVI.
      DESIGN: All octogenarians with a risk profile considered by the Heart Team to be
      unacceptable for surgery entered in this registry. QOL was assessed by
      questionnaires concerning physical and psychic performance. PATIENTS: A hundred
      forty-five octogenarians (age: 84.7 +/- 3.4 years; male: 48.3%) underwent TAVI
      for AS (97.2%) or isolated AR (2.8%). NYHA class: 2.8 +/- 0.6; Logistic
      EuroScore: 26.1 +/- 16.7; STS score: 9.2 +/- 7.7.Echocardiographic assessments
      included AVA (0.77 +/- 0.21 cm2), mean/peak gradients (54.5 +/- 12.2/88 +/- 19.5
      mm Hg), LVEF (21%=EF <= 40%), sPAP (43.1 +/- 11.6 mmHg). INTERVENTIONS: All pts
      underwent successful TAVI using Edward-SAPIEN valve (71.2%) or Medtronic
      CoreValve (28.8%). MAIN OUTCOME MEASURES: Rates of mortality at 30 days, 6 months
      and 1 year were 2.8%, 11.2% and 17.5%. RESULTS: At 16-month follow up, 85.5%
      survived showing improved NYHA class (2.8 +/- 0.6 vs 1.5 +/- 0.7; p<0.001),
      decreased sPAP (43.1 +/- 11.6 mm Hg vs 37.1 +/- 7.7 mm Hg; p<0.001) and increased
      LVEF in those with EF <= 40% (34.9 +/- 6% vs 43.5 +/- 14.4%; p=0.006). Concerning
      QOL, 49% walked unassisted, 79% (39.5% among pts >= 85 years) reported self
      awareness improvement; QOL was reported as "good" in 58% (31.4% among pts >= 85
      years), "acceptable according to age" in 34% (16% among pts >= 85 years) and
      "bad" in 8%. CONCLUSION: TAVI procedures improve clinical outcome and subjective
      health-related QOL in very elderly patients with symptomatic AS.

PMID- 23146288
TI  - Association between the SPRY1 gene polymorphism and obesity-related traits and
      osteoporosis in Korean women.
AB  - BACKGROUND: Emerging evidence has revealed a close relationship between obesity
      and osteoporosis. It was reported recently that conditional knockout of the Spry1
      gene in mice adipocytes causes an increase in body fat and a decrease in bone
      mass, and that these phenotypes are rescued by Spry1 overexpression in adipose
      tissue. In this study, we investigated whether genetic variation in the human
      SPRY1 gene is associated with obesity-related phenotypes and/or osteoporosis in
      humans. METHODS: We performed a candidate gene association analysis between the
      four single nucleotide polymorphisms (SNPs) and 14 imputed SNPs in the SPRY1 gene
      and obesity-related traits and osteoporosis in a Korean women cohort (3013
      subjects). RESULTS: All four SPRY1 gene SNPs were significantly associated with
      either obesity-related traits or osteoporosis. The TGCC haplotype in the SRPY1
      gene showed simultaneous association with an increased risk for obesity-related
      traits, percentage body fat (p=0.0087) and percentage abdominal fat (p=0.047),
      and osteoporosis (odds ratio=1.50; p=0.025) in the recessive genetic model.
      CONCLUSIONS: Our results support a previous finding in conditional Spry1 gene
      knockout mice and suggest that the SPRY1 gene is an important genetic factor for
      determining the risk of both obesity and osteoporosis in humans.

PMID- 23146289
TI  - No accumulation of globotriaosylceramide in the heart of a patient with the E66Q
      mutation in the alpha-galactosidase A gene.
AB  - BACKGROUND: Fabry disease is an X-linked lysosomal disorder resulting from
      mutations in the alpha-galactosidase A (GLA) gene. Recent reports described that
      the E66Q mutation of GLA is not a disease-causing mutation. However, no
      pathological study was reported. We carried out pathological studies using a
      cardiac biopsy specimen from a patient with the E66Q mutation. MATERIALS AND
      METHODS: The case was a 34 year old male patient with end-stage renal failure and
      cardiomegaly. He was diagnosed with gout at 15 years of age and hemodialysis was
      started for gouty nephropathy from 31 years of age. He was suspected of having
      Fabry disease as the result of a screening study for Fabry disease in patients
      with end-stage renal failure and was referred to our hospital for mutation
      analysis of the GLA gene. We carried out enzymatic and genetic analysis for GLA
      and pathological studies of a cardiac biopsy specimen. RESULTS: The patient had
      the E66Q mutation in the GLA gene. GLA activity in leukocytes was 36.2% of the
      average of normal controls. The pathological study of the cardiac biopsy sample
      showed no characteristic findings of Fabry disease. The immunohistochemistry for
      GL3 of the cardiac biopsy sample showed no positive cells. CONCLUSION: Although
      the E66Q mutation reduced enzyme activity, the characteristic pathological
      findings of Fabry disease and the abnormal accumulation of GL3 were not detected
      in cardiac tissues. The E66Q mutation of the GLA gene is thought to be a
      functional polymorphism based on enzymatic and pathological studies.

PMID- 23146290
TI  - Severe phenotypic spectrum of mevalonate kinase deficiency with minimal mevalonic
      aciduria.
AB  - Mevalonate kinase deficiency is a rare autosomal recessively inherited organic
      aciduria with a complex multi-systemic phenotype. We describe two deceased
      patients with clinically severe mevalonate kinase (MK) deficiency confirmed by MK
      mutation analysis. The phenotype in our patients ranged from neonatal hydrops in
      the first patient to severe failure to thrive, hepatosplenomegaly, recurrent
      febrile episodes and lymphadenopathy in the second. Both infants excreted
      relatively low amounts of mevalonic acid intermittently.

PMID- 23146291
TI  - Effects of exercise training during infusion on late-onset Pompe disease patients
      receiving enzyme replacement therapy.
AB  - Pompe disease is an autosomal recessive disorder caused by the deficiency of acid
      alpha-glucosidase resulting in lysosomal accumulation of glycogen and abnormal
      autophagic function. The late-onset form of the disease is characterized by
      progressive skeletal and respiratory muscle dysfunction. Enzyme replacement
      therapy (ERT, Genzyme Corporation, Cambridge, MA, USA) was recently introduced
      and resulted in significant prolongation of the life expectancy of the patients
      with the infantile form while the results were less significant for the late
      onset form. It has been postulated that the weak influence of ERT in late-onset
      patients might be due to a non-effective delivery of the recombinant enzyme to
      the skeletal muscles perhaps due to the relatively low blood flow to the resting
      skeletal muscles during infusion. Exercise training acutely increases the blood
      flow to the exercising muscles. Thus, it was hypothesized that exercise training
      during enzyme infusion might increase the effectiveness of the ERT therapy. Five
      late-onset Pompe disease patients receiving ERT and following regular exercise
      training for approximately 10 months, followed a 6-month period of exercise
      training during infusion of the recombinant enzyme. Before and after this period,
      body composition, isometric strength and 6 minute walking distance were
      determined. Analysis of the results revealed that none of these parameters
      changed significantly after the 6-month intervention period (e.g. 6 minute
      walking distance before: 532+/-31 m, vs. after: 527+/-29 m, P=0.246). These
      results suggest that exercise training during infusion may not add significant
      functional changes in late-onset Pompe patients receiving ERT and undergoing
      regular exercise training.

PMID- 23146292
TI  - Sensitivity and specificity of the Mood Disorder Questionnaire as a screening
      tool for bipolar disorder during pregnancy and the postpartum period.
AB  - BACKGROUND: Previous studies have shown that one-quarter of women with bipolar
      disorder relapse during pregnancy, and nearly half of bipolar women relapse
      during the postpartum period. The perinatal period is also associated with an
      elevated risk for new-onset mood disorder. Bipolar disorder is often
      unrecognized, and there is often a significant delay between illness onset and
      proper diagnosis and treatment. The objective of this cross-sectional
      psychometric study was to investigate the use of the Mood Disorder Questionnaire
      (MDQ) as a screening tool for bipolar disorder in a community-based population of
      pregnant and postpartum women. METHOD: 150 women with a mean age of 30.1 years
      (standard deviation = 5.5 years; range, 17-43 years) who had been referred to a
      women's mental health program for psychiatric assessment during pregnancy (n =
      95) or the postpartum period (n = 55) were enrolled between June 2010 and
      December 2011. All women completed the MDQ on the day of their first assessment,
      and the sensitivity and specificity of the MDQ were calculated against DSM-IV
      based clinical diagnoses provided by experienced psychiatrists. RESULTS: A total
      of 18 women (12% of the sample) were diagnosed with bipolar disorder (6 with
      bipolar I disorder, 10 with bipolar II disorder, and 2 with bipolar disorder not
      otherwise specified). The traditional scoring of the MDQ yielded poor sensitivity
      (39%) and excellent specificity (91%). The best-fitting model was a modified
      scoring algorithm using cutoff scores of 7 or more symptoms on the MDQ without
      the supplementary questions, yielding excellent sensitivity (89%) and specificity
      (84%). CONCLUSIONS: The MDQ is a useful instrument for screening for bipolar
      disorder during both pregnancy and the postpartum period. Considering that
      perinatal women have an elevated risk of both first-onset and relapse of bipolar
      disorder, particularly during the postpartum period, routine use of screening
      tools in perinatal programs is encouraged.

PMID- 23146293
TI  - Effect of ranolazine on arterial endothelial function in patients with type 2
      diabetes mellitus.
AB  - OBJECTIVE: To assess the effect of ranolazine on systemic vascular function in
      patients with type II diabetes mellitus (T2DM). METHODS: We randomized 30
      consecutive T2DM patients with no evidence of cardiovascular disease and no
      insulin therapy to receive one of the following 3 forms of treatment in a blinded
      fashion: ranolazine, 375 mg bid for 3 weeks (group 1); ranolazine, 375 mg bid for
      2 weeks, followed by placebo bid for 1 week (group 2); placebo bid for 3 weeks
      (group 3). Flow-mediated dilation (FMD) and nitrate-mediated dilation (NMD) of
      the right brachial artery were assessed at baseline and after 48 h, and 2 and 3
      weeks. RESULTS: FMD and NMD were similar among groups at baseline. Compared to
      the basal value, FMD significantly improved after 2 weeks in group 1 and in group
      2 (p < 0.01 for both), but not in group 3. At 3 weeks, FMD remained improved,
      compared to baseline, in group 1 (p < 0.05), whereas returned to basal values in
      group 2 (p = 0.89 vs. baseline). No changes in NMD were observed in any group.
      CONCLUSIONS: In this controlled study, ranolazine was able to improve endothelial
      function in T2DM patients.

PMID- 23146294
TI  - Cough--another important factor in extubation readiness in critically ill
      patients.

PMID- 23146295
TI  - Prenatal diagnosis of a paraurethral cyst.
AB  - Paraurethral cysts arising from Skene's gland are a rare cause of urogenital
      masses in the neonate. We report the case of a pelvic mass noted at the vaginal
      introitus on prenatal ultrasound that following delivery was found to be a
      paraurethral cyst. On prenatal ultrasound, there was no evidence of involvement
      of the urinary, gastrointestinal, or upper genital tract. Serial ultrasounds
      demonstrated slight enlargement of the cyst without other changes. The patient
      delivered at 33 weeks and postnatal evaluation demonstrated a paraurethral cyst.
      The cyst was managed expectantly and drained spontaneously on the second day of
      life with complete resolution.

PMID- 23146296
TI  - Timing and nature of reconstructive surgery for disorders of sex development -
      introduction.
AB  - The ideal timing and nature of surgical reconstruction in individuals with
      Disorders of Sex Development (DSD) is highly controversial. Despite the
      increasing number of publications on this topic, evidence-based recommendations
      still cannot be made. However it is generally accepted that optimal care for DSD
      requires an experienced multidisciplinary team. This means that surgical
      decisions are now made within the context of a multidisciplinary team and all
      members of the team - and not just specialist surgeons - may be called upon to
      discuss choices for surgery with patients and parents. To do this well, every
      clinician in the team should have an understanding of the range of techniques
      available for genital surgery, the risks and benefits of procedures and the
      controversies surrounding timing of surgery. The aim of this paper is to give an
      overview of the variety of surgical procedures in current use and in what
      situation a particular technique would be indicated. The short-term risks and
      benefits are described and where available long-term outcome data is discussed.
      To date, discussions surrounding genital surgery have been led primarily by
      surgeons. Some non-surgical clinicians have expressed unease about decision
      making in genital surgery but have felt ill equipped to comment on an area with
      which they are unfamiliar. This review gives a detailed explanation of current
      surgical practice offered in a specialized center for DSD and such information
      should facilitate a more balanced discussion.

PMID- 23146297
TI  - Neuroproteomics: an insight into ALS.
AB  - Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease of
      unknown aetiology. Diagnosis is made through physical examination,
      electrophysiological findings, and by excluding other conditions. There is not a
      single biomarker that concludes the diagnosis. The aim of this  study was to
      investigate differentially expressed proteins in cerebrospinal fluid (CSF) of ALS
      patients compared to control subjects, with the purpose to identify a panel of
      possible biomarkers for the disease. The differentially expressed spots/proteins
      were submitted to two-dimensional (2D)  electrophoresis and recognized with
      matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF) mass
      spectrometry. Parkin-like and many iron and zinc binding were some of the
      proteins found in ALS CSF. Parkin is a ligase involved in ubiquitin-proteasome
      pathway and  mutations in the parkin gene are the most common cause of recessive
      familial Parkinson's disease. Iron and zinc are involved with many important
      metabolic processes and are related to neurodegenerative disease. Common features
      of ALS comprise failure of the ubiquitin-proteasome  system and increased levels
      of metal ions in the brain. Therefore, the identification of these proteins can
      be a significant step in ALS research. These and other identified proteins are
      discussed in this study.

PMID- 23146298
TI  - A community-based epidemiological study of peripheral neuropathies in Assiut,
      Egypt.
AB  - BACKGROUND: There is very little published information about the prevalence,
      patterns, and predictors of peripheral neuropathies. The current study is a
      community-based survey was conducted in the Assiut Governorate to estimate their
      prevalence and clinical profile. MATERIAL AND METHODS: A door-to-door study was
      carried out on 42,223 persons from rural and urban communities in the Assiut
      Governorate, Egypt. There were 13,288 (31.5%) subjects from the urban and 28,935
      (68.5%) from the rural area. All subjects filled in a questionnaire designed
      specifically for diagnosis of peripheral neuropathy. Positive cases were then
      given a complete medical and neurological examination, routine laboratory tests,
      neurophysiology, and neuroimaging (magnetic resonance). RESULTS: The crude
      prevalence rate (CPR) of peripheral neuropathy was 3181/100,000 inhabitants.
      There was a significantly higher prevalence in the rural compared with the urban
      population (3795 versus 1844/100,000) and in females than males (4473 versus
      1943/100,000; P<0.001 for both). The most common type reported was entrapment
      neuropathy (736 cases with CPR of 1743/100,000), particularly carpal tunnel
      syndrome (1686/100,000). Diabetic neuropathy was the most common non-compressive
      neuropathy with a CPR of 649/100,000. Type II diabetes was recorded in 241
      patients with a CPR of 571/100,000. Compressive radiculopathy had a crude
      prevalence of 358/100,000; traumatic and iatrogenic radiculopathy had a
      prevalence rate of 149/100,000. Less common conditions were: uremic neuropathy
      (21/100,000) hepatic neuropathy (14/100,000), Bell's palsy (28/100,000), Guillian
      Barre' syndrome (12/100,000), chronic inflammatory demyelinating polyneuropathy
      (12/100,000), hereditary sensory motor neuropathy (12/100,000), and idiopathic
      neuropathy (92/100,000). CONCLUSION: The overall prevalence of peripheral
      neuropathies was high in comparison to other studies. Entrapment neuropathy,
      diabetic neuropathy, and spondylotic radiculopathy were the most common. Overall,
      the prevalence of peripheral neuropathy was higher in the rural than in the urban
      population.

PMID- 23146299
TI  - Regional variations in brain oxygenation during temporary clipping in aneurysm
      surgery.
AB  - OBJECTIVES: Brain tissue oxygen concentration (PbtO(2)) monitoring has been used
      in aneurysm surgery to detect decreased brain oxygenation during temporary
      clipping. The effects of circulatory interruption according to different aneurysm
      locations have not been established. In this work, variations in PbtO(2) during
      temporary clipping were studied in anterior communicating (AcomA), posterior
      communicating (PcomA) origin, and middle cerebral artery (MCA) aneurysm surgery.
      METHODS: PbtO(2) was monitored during surgery of 41 patients; aneurysms were
      located in the AcomA (10 cases), origin of PcomA (8 cases), and MCA bifurcation
      (23 cases). Temporary clips were used in all cases. Variations in PbtO(2) values
      obtained during application of temporary clips were evaluated and studied
      according to the duration and type of circulatory interruption for each aneurysm
      location. RESULTS: In AcomA aneurysm surgery, a significant decrease in PbtO(2)
      values was found in 31% of the periods of temporary clipping, whereas in PcomA
      and MCA aneurysm surgery, significant decreases were found in all temporary clip
      applications (100%). In MCA aneurysms, the amplitude of decrease in PbtO(2) was
      higher when the circulatory interruption lasted for 2 or more minutes, compared
      with shorter periods of temporary clipping. DISCUSSION: During temporary
      clipping, different variations in PbtO(2) values were obtained when comparing
      frontal and temporal regions of monitoring: in MCA and PcomA origin aneurysms,
      significant variations were registered in all periods of temporary regional
      circulatory interruption, but the same results were not found in frontal
      monitoring for AcomA aneurysm surgery.

PMID- 23146300
TI  - Protective effect of BAG5 on MPP+-induced apoptosis in PC12 cells.
AB  - OBJECTIVES: Parkinson's disease (PD) is the most common neurodegenerative disease
      in humans, and an abundance of evidence has implicated apoptosis signaling
      pathways in the neurodegeneration of PD. The purpose of this study was to assess
      the role of B-cell lymphoma 2 (Bcl-2)-associated  athanogene 5 (BAG5) protein,
      which was previously confirmed to play an important role in the pathogenesis of
      PD, in the regulation of apoptosis induced by 1-methyl-4-phenyl-pyridinium
      (MPP(+)) in PC12 cells. METHODS: PC12 cells were treated with MPP(+) for 48 hours
      to induce apoptosis, and activation of Bcl-2, Bcl-xl, and caspase 3 was measured
      by western blot. RESULTS: The upregulation of BAG5 in PC12 cells inhibited
      apoptosis and increased the expression of anti-apoptotic proteins, including Bcl
      2 and Bcl-xl, after MPP(+) treatment.  In addition, downregulation of BAG5 in
      PC12 cells enhanced apoptosis and decreased the expression of these proteins
      after MPP(+) treatment. DISCUSSION: The data suggest that BAG5 inhibits MPP(+)
      induced apoptosis through both endogenous and mitochondria-mediated  pathways of
      apoptosis. Through this mechanism, the upregulation of BAG5 levels may occur
      through its anti-apoptotic activity in PD.

PMID- 23146301
TI  - Differentiation of primary central nervous system lymphomas from high grade
      astrocytomas by qualitative analysis of the signal intensity curves derived from
      dynamic susceptibility-contrast magnetic resonance imaging.
AB  - OBJECTIVE: Preoperative differentiation between primary central nervous system
      lymphoma (PCNSL) and high grade astrocytoma (HGA) on conventional magnetic
      resonance imaging (MRI) can be difficult and even impossible. However,
      differentiation is important to guide therapeutic strategy. Several authors have
      reported the leakage pattern in dynamic susceptibility-contrast (DSC)-MRI in
      PCNSL. It describes the shape of the signal intensity curve which does not return
      to the baseline after the first pass of the bolus of contrast agent but crosses
      above it and sometimes even slopes up. In this retrospective study, our goal was
      to define the sensitivity and specificity of this sign. MATERIAL AND METHODS:
      Patients with first ever diagnosed PCNSL and HGA who were treatment naive and
      received DSC-MRI were included. In all patients, a histological specimen was
      available. Patients did not receive corticosteroids prior to imaging and were HIV
      negative. The presence of a leakage pattern was assessed by two neuroradiologists
      working in consensus and correlated with the histological diagnosis. RESULTS:
      Nine patients with PCNSL (2 women, 7 men, age 59 +/- 10 years) and 14 patients
      with HGA (3 women, 11 men, age 58 +/- 17 years) were included. Six of the
      patients with PCNSL exhibited a leakage pattern, while only two patients with HGA
      did (P = 0.0227, Fischer's exact test). Sensitivity was 0.67, and specificity was
      0.86. DISCUSSION: Although the leakage pattern does not prove PCNSL, it is an
      important diagnostic clue and can be easily assessed.

PMID- 23146302
TI  - Neurochemical correlates of cognitive dysfunction in patients with leukoaraiosis:
      a proton magnetic resonance spectroscopy study.
AB  - OBJECTIVES: Leukoaraiosis (LA) is a common radiological finding in the elderly
      and may reflect cerebral small vessel disease (SVD). Although SVD has been
      identified as a major cause of vascular cognitive impairment or vascular
      dementia, the mechanisms for this association remain unclear. We therefore aimed
      to measure brain metabolites in LA using proton magnetic resonance spectroscopy
      ((1)H-MRS) as to determine the relationship between cognitive function and
      neurochemical white matter profile. METHODS: We recruited 23 patients with LA and
      23 age- and sex-matched healthy controls consecutively. Multi-voxel (1)H-MRS was
      performed with a volume of interest located in centrum semiovale that contained
      mainly white matter voxels. Three main ratios of N-acetyl aspartate (NAA)/Cr,
      choline (Cho)/Cr and NAA/Cho were obtained. Spearman rank correlation
      coefficients were calculated between the cognitive function and the measured
      metabolite ratios. RESULTS: We found significantly lower levels of NAA/Cho and
      NAA/Cr ratios in lesioned white matter in patients with LA than healthy controls
      (P<0.05). The ratios of NAA/Cho and NAA/Cr in normal appearing white matter
      (NAWM) were higher than lesioned white matter and lower than controls, but this
      difference was not significant (P>0.05). There was a positive relationship
      between Mini-Mental State Examination (MMSE) and NAA/Cho in NAWM (r = 0.417, P =
      0.048), and also a positive relationship between MMSE and NAA/Cr in lesioned
      white matter (r = 0.551, P = 0.006) in patients with LA. A positive relationship
      between the Z scores of the executive function and NAA/Cho in lesioned white
      matter (r = 0.557, P = 0.006) was also found. CONCLUSION: The main finding of
      this study was a significant reduction in the ratios of NAA/Cr and NAA/Cho in
      lesioned white matter, which indicates a marker of neuronal loss or dysfunction
      in patients with LA, which was correlated with cognitive function. This
      relationship between cognitive function and metabolic changes suggests that (1)H
      MRS can be explored as a marker for cognitive dysfunction in patients with LA.

PMID- 23146303
TI  - Preventive effects of AdR-siPTEN through the regulation of NMDA receptor NR2B
      subunit in trigeminal ganglia of migraine rats.
AB  - OBJECTIVE: Migraine is a refractory disease that is due to neuronal
      hyperexcitability, and has high incidence, mortality, and disability rates. The N
      methyl-D-aspartate receptor 2B (NR2B) subunit has been found to play an important
      role in the pathogenesis of migraine. There is evidence suggesting that a tumor
      suppressor phosphatase and tensin homolog (PTEN) can confer a neuroprotective
      effect on cerebral ischemic injury by regulating NR2B levels. However, the role
      of PTEN in migraines is still unclear. This study aimed to define whether PTEN is
      involved in the pathogenesis of migraine through modulating NR2B, nitric oxide
      synthase (NOS), and nitric oxide (NO) in the trigeminal ganglia of rats with
      glyceryl trinitrate-induced migraine. METHODS: Adenovirus-expressing siPTEN or
      RFP was independently injected into the Sp5 (spinal trigeminal nucleus) of rats
      suffering from migraines. Seven days later, tactile sensory testing was performed
      to detect the tactile threshold. Immunofluorescence assay, western blot assay, RT
      PCR, and biochemical examination were done to measure PTEN, NR2B, NOS, and NO
      levels in the trigeminal ganglia of migraine rats. RESULTS: NR2B, NOS, and NO
      levels significantly (P<0.05) decreased in the trigeminal ganglia of migraine
      affected rats pretreated with adenovirus-expressing siPTEN. CONCLUSION: These
      results suggest that PTEN in trigeminal ganglia is implicated in the pathogenesis
      of migraine, and PTEN may be a novel and promising candidate for future treatment
      and/or prevention of migraine via regulating NR2B and decreasing NO production in
      trigeminal ganglia.

PMID- 23146304
TI  - Hydrogen rich saline reduces immune-mediated brain injury in rats with acute
      carbon monoxide poisoning.
AB  - OBJECTIVES: This experiment was designed to determine whether hydrogen (H(2))
      rich saline can ameliorate brain abnormalities in a rat model with acute carbon
      monoxide (CO) poisoning. METHODS: Sprague-Dawley male rats were used for CO
      poisoning and H(2) rich saline treatment. Changes in neurons, microglias, and
      myelin sheath were observed by electron microscope. Neuron loss was assessed by
      Nissl staining. Antioxidant capacities were evaluated by studying superoxide
      dismutase activities and malondialdehyde concentration in the brain and serum.
      Infiltration of macrophages, expression of immune-associated cytokines (MIP-1
      alpha and ICAM-1), and changes in myelin basic protein (MBP) were monitored by
      immunohistochemical staining and western blotting. RESULTS: CO-exposed rats
      showed the increase in neuron loss and the decrease in antioxidant capacities.
      And H(2) rich saline given after CO poisoning can prevent the alterations
      mentioned above. CO-mediated oxidative stress caused alterations in MBP, which
      initiated an adaptive immunological response that led to brain injury. MBP from
      H(2) rich saline-treated, CO-exposed rats was recognized normally by
      immunohistochemical staining and western blotting. Electron microscope
      observation from CO-exposed rats showed an apparent aggregation of microglias.
      Macrophages from CO-exposed rats were significantly more than those from H(2)
      rich saline-treated and control rats, and the immunofluorescence observation
      showed that macrophages were similar to microglias in type. Expression levels of
      MIP-1-alpha and ICAM-1 increased in the brains of CO-poisoned rats and H(2) rich
      saline treatment decreased the levels. DISCUSSION: The results indicate that H(2)
      rich saline prevents immune-mediated brain injury after CO poisoning.

PMID- 23146305
TI  - Evaluation of the bioconversion of genetically modified switchgrass using
      simultaneous saccharification and fermentation and a consolidated bioprocessing
      approach.
AB  - BACKGROUND: The inherent recalcitrance of lignocellulosic biomass is one of the
      major economic hurdles for the production of fuels and chemicals from biomass.
      Additionally, lignin is recognized as having a negative impact on enzymatic
      hydrolysis of biomass, and as a result much interest has been placed on modifying
      the lignin pathway to improve bioconversion of lignocellulosic feedstocks.
      RESULTS: Down-regulation of the caffeic acid 3-O-methyltransferase (COMT) gene in
      the lignin pathway yielded switchgrass (Panicum virgatum) that was more
      susceptible to bioconversion after dilute acid pretreatment. Here we examined the
      response of these plant lines to milder pretreatment conditions with yeast-based
      simultaneous saccharification and fermentation and a consolidated bioprocessing
      approach using Clostridium thermocellum, Caldicellulosiruptor bescii and
      Caldicellulosiruptor obsidiansis. Unlike the S. cerevisiae SSF conversions,
      fermentations of pretreated transgenic switchgrass with C. thermocellum showed an
      apparent inhibition of fermentation not observed in the wild-type switchgrass.
      This inhibition can be eliminated by hot water extraction of the pretreated
      biomass, which resulted in superior conversion yield with transgenic versus wild
      type switchgrass for C. thermocellum, exceeding the yeast-based SSF yield.
      Further fermentation evaluation of the transgenic switchgrass indicated
      differential inhibition for the Caldicellulosiruptor sp. strains, which could not
      be rectified by additional processing conditions. Gas chromatography-mass
      spectrometry (GC-MS) metabolite profiling was used to examine the fermentation
      broth to elucidate the relative abundance of lignin derived aromatic compounds.
      The types and abundance of fermentation-derived-lignin constituents varied
      between C. thermocellum and each of the Caldicellulosiruptor sp. strains.
      CONCLUSIONS: The down-regulation of the COMT gene improves the bioconversion of
      switchgrass relative to the wild-type regardless of the pretreatment condition or
      fermentation microorganism. However, bacterial fermentations demonstrated strain
      dependent sensitivity to the COMT transgenic biomass, likely due to additional
      soluble lignin pathway-derived constituents resulting from the COMT gene
      disruption. Removal of these inhibitory constituents permitted completion of
      fermentation by C. thermocellum, but not by the Caldicellulosiruptor sp. strains.
      The reason for this difference in performance is currently unknown.

PMID- 23146306
TI  - Melanoma stem cells in experimental melanoma are killed by radioimmunotherapy.
AB  - INTRODUCTION: In spite of recently approved B-RAF inhibitors and immunomodulating
      antibodies, metastatic melanoma has poor prognosis and novel treatments are
      needed. Melanoma stem cells (MSC) have been implicated in the resistance of this
      tumor to chemotherapy. Recently we demonstrated in a Phase I clinical trial in
      patients with metastatic melanoma that radioimmunotherapy (RIT) with 188
      Rhenium((188)Re)-6D2 antibody to melanin was a safe and effective modality. Here
      we investigated the interaction of MSC with RIT as a possible mechanism for RIT
      efficacy. METHODS: Mice bearing A2058 melanoma xenografts were treated with
      either 1.5 mCi (188)Re-6D2 antibody, saline, unlabeled 6D2 antibody or (188)Re
      labeled non-specific IgM. RESULTS: On Day 28 post-treatment the tumor size in the
      RIT group was 4-times less than in controls (P<0.001). The tumors were analyzed
      by immunohistochemistry and FACS for two MSC markers--chemoresistance mediator
      ABCB5 and H3K4 demethylase JARID1B. There were no significant differences between
      RIT and control groups in percentage of ABCB5 or JARID1B-positive cells in the
      tumor population. Our results demonstrate that unlike chemotherapy, which kills
      tumor cells but leaves behind MSC leading to recurrence, RIT kills MSC at the
      same rate as the rest of tumor cells. CONCLUSIONS: These results have two main
      implications for melanoma treatment and possibly other cancers. First, the
      susceptibility of ABCB5+ and JARID1B+cells to RIT in melanoma might be indicative
      of their susceptibility to antibody-targeted radiation in other cancers where
      they are present as well. Second, specifically targeting cancer stem cells with
      radiolabeled antibodies to ABCB5 or JARID1B might help to completely eradicate
      cancer stem cells in various cancers.

PMID- 23146307
TI  - (99m)Tc-daunorubicin a potential brain imaging and theranostic agent: synthesis,
      quality control, characterization, biodistribution and scintigraphy.
AB  - Daunorubicin is a chemotherapeutic antibiotic of the anthracycline family used
      for the treatment of many type of cancers when doxorubicin or other less
      effective drugs cannot be used. The aim of the present study was labeling of
      Daunorubicin with (99m)Tc, quality control, characterization, and biodistribution
      of radiolabeled Daunorubicin. Labeling efficiency was determined by ascending
      paper chromatography. All the experiments were performed at room temperature (25
      degrees C+/-2 degrees C). More than 96% labeling efficiency with (99m)Tc was
      achieved at pH 5-6, 2-4 MUg stannous chloride and 300 MUg of ligand in few
      minutes. The characterization of the compound was performed by using HPLC,
      electrophoresis and shake flask assay. Electrophoresis indicates that Tc-99m
      Daunorubicin is neutral, HPLC confirms the single specie of the labeled compound,
      while shake flask assay confirms high lipophilicity. The biodistribution studies
      of (99m)Tc-Daunorubicin were performed in rats. Significantly higher accumulation
      of (99m)Tc-Daunorubicin was seen in brain of normal rats. Scintigraphy was also
      indicating higher accumulation of (99m)Tc-Daunorubicin in brain of normal
      rabbits.

PMID- 23146308
TI  - Criteria of validity in experimental psychopathology: application to models of
      anxiety and depression.
AB  - The modeling of abnormal behavior in 'normal' subjects (often animals) has a long
      history in pharmacological research for the screening of novel drug compounds.
      Systematic criteria have been outlined in that literature to estimate the
      external validity of a model, that is to estimate how closely the model is linked
      to the disorder of interest. Experimental psychopathology (EPP) also uses
      behavioral models to study the psychological processes that underlie abnormal
      behavior. Although EPP researchers may occasionally feel uneasy about the
      validity of the model that they use, the issue has not received direct attention
      in this literature. Here, we review the criteria of validity as set out in
      pharmacology research (face, predictive and construct validity) and discuss their
      relevance for EPP research. Furthermore, we propose diagnostic validity as an
      additional criterion of external validity that is relevant to EPP research. We
      evaluate two models for the study of anxiety and depression, and show that they
      have good face, diagnostic and construct validity. However, EPP research
      generally lacks direct tests of predictive validity. We conclude that combined
      evaluations of predictive, diagnostic and construct validity provide a sound
      basis to infer the external validity of behavioral models in EPP research. 

PMID- 23146309
TI  - Host factors and measles virus replication.
AB  - This review takes a general approach to describing host cell factors that
      facilitate measles virus (MeV) infection and replication. It relates our current
      understanding of MeV entry receptors, with emphasis on how these host cell
      surface proteins contribute to pathogenesis within its host. The roles of
      SLAM/CD150 lymphocyte receptor and the newly discovered epithelial receptor
      PVRL4/nectin-4 are highlighted. Host cell factors such as HSP72, Prdx1, tubulin,
      casein kinase, and actin, which are known to impact viral RNA synthesis and
      virion assembly, are also discussed. Finally the review describes strategies used
      by measles virus to circumvent innate immunity and confound the effects of
      interferon within the host cell. Proteomic studies and genome wide RNAi screens
      will undoubtedly advance our knowledge in the future.

PMID- 23146311
TI  - Japanese quail acute exposure to methamidophos: experimental design, lethal, sub
      lethal effects and cholinesterase biochemical and histochemical expression.
AB  - We exposed the Japanese quail (Coturnix coturnix japonica) to the organophosphate
      methamidophos using acute oral test. Mortality and sub-lethal effects were
      recorded in accordance to internationally accepted protocols. In addition
      cholinesterases were biochemically estimated in tissues of the quail: brain,
      liver and plasma. Furthermore, brain, liver and duodenum cryostat sections were
      processed for cholinesterase histochemistry using various substrates and
      inhibitors. Mortalities occurred mainly in the first 1-2h following application.
      Sub-lethal effects, such as ataxia, ruffled feathers, tremor, salivation and
      reduced or no reaction to external stimuli were observed. Biochemical analysis in
      the brain, liver and plasma indicates a strong cholinesterase dependent
      inhibition with respect to mortality and sub-lethal effects of the quail. The
      histochemical staining also indicated a strong cholinesterase inhibition in the
      organs examined and the analysis of the stained sections allowed for an
      estimation and interpretation of the intoxication effects of methamidophos, in
      combination with tissue morphology visible by Haematoxylin and Eosin staining. We
      conclude that the use of biochemistry and histochemistry for the biomarker
      cholinesterase, may constitute a significantly novel approach for understanding
      the results obtained by the acute oral test employed in order to assess the
      effects of methamidophos and other chemicals known to inhibit this very important
      nervous system enzyme.

PMID- 23146312
TI  - Carbonaceous soil amendments to biofortify crop plants with zinc.
AB  - Carbonaceous soil amendments, comprising mixtures of biosolids and biochar, have
      been demonstrated to improve fertility while reducing nitrate leaching. We aimed
      to determine the efficacy of a biosolids/biochar soil amendment in
      biofortification of vegetables with Zn, an element that is deficient in one third
      of humanity. We grew beetroot (Beta vulgaris), spinach (Spinacia oleracea),
      radish (Raphanus sativus), broccoli (Brassica oleracea), carrot (Daucus carota),
      leek (Allium ampeloprsum), onion (Allium cepa), lettuce (Lactuca sativa), corn
      (Zea mays), tomato (Solanum lycopersicum), and courgette (also called zucchini -
      Cucurbita pepo) in an unamended soil (silt loam, pH 5.6), and soil amended (by
      volume) with 10% biosolids, 20% biochar, and 10% biosolids+20% biochar. The
      biosolids and biosolids+biochar treatments significantly increased the biomass
      and Zn concentration of most species, with a large interspecific variation.
      Beetroot showed the greatest increase, with dry weight Zn concentrations of up to
      178 and 1200 mg kg(-1) in the bulbs and leaves respectively. Cadmium, Cu and Pb
      were below guideline levels in all samples, except the leaves of spinach and
      beetroot, which slightly exceeded the World Health Organisation's maximum
      permitted concentration of 0.1 mg Cd kg(-1) fresh weight. A mixture of biosolids
      and biochar is an effective means to biofortify crops with edible leaves as well
      as beetroot with Zn. Future research should investigate the efficacy of the
      system in other soil types and the role of biochar in the
      immobilisation/inactivation of organic contaminants and pathogens contained
      within the biosolids.

PMID- 23146313
TI  - Hand and wrist arthralgia in systemic lupus erythematosus is associated to
      ultrasonographic abnormalities.
AB  - OBJECTIVE: Systemic lupus erythematosus (SLE) is an autoimmune disease which may
      has joint impairment. Often, SLE patients complain of hand and wrist arthralgia
      (HA). Usually, these patients do not show any swelling in the physical exam. Our
      aim was to demonstrate Power Doppler Ultrasound (PDUS) abnormalities in SLE
      patients with HA. METHODS: We recruited 58 consecutive SLE patients and divided
      them into two groups: case group (n = 28) were patients with HA, and control
      group (n = 30) were patients without HA. We also collected socio-demographic and
      disease activity data, biological markers and SLEDAI index. We evaluated
      disability and quality of life by mHAQ and SF-12, respectively. We performed a
      bilateral hand and wrist PDUS on all patients. PDUS findings were based in
      OMERACT-7 group criteria. RESULTS: We found PDUS abnormalities in most of SLE
      patients who suffered HA, when compared to SLE controls (P < 0.001). The main
      findings in Case Group were: tenosynovitis (39.2%), synovial effusion or
      hypertrophy (25%) and active synovitis (14.2%). SLEDAI score and dsDNA antibodies
      were related to the presence of PDUS abnormalities (P < 0.05 and P < 0.001,
      respectively). We also found worse physical SF-12 (P < 0.05) and mHAQ (NS) scores
      in case group. CONCLUSIONS: SLE patients who present HA have more PDUS
      abnormalities. These findings are associated with a higher SLEDAI score and dsDNA
      antibodies. This articular affection may contribute to a worsened functional
      ability and a lower quality of life. PDUS seems to be a reliable tool in the
      assessment of SLE patients with HA.

PMID- 23146314
TI  - The Chinese version of the Addiction Severity Index (ASI-C): reliability,
      validity, and responsiveness in Chinese patients with alcohol dependence.
AB  - We evaluated the reliability, validity, and responsiveness of the Chinese version
      of the 5th edition Addiction Severity Index (ASI-C-5) in Chinese male alcohol
      dependent inpatients. Three hundred and fifty-four inpatients with alcohol
      dependence from five regions of China were interviewed in person by five trained
      interviewers using the ASI-C-5. Responses were then analyzed for internal
      consistency reliability, discriminant validity, criterion validity, and
      responsiveness. Forty subjects were re-interviewed 7 days later to assess test
      retest reliability. The ASI-C-5 had good internal consistency, with an overall
      standardized Cronbach's alpha of 0.79. The Cronbach's alpha values for internal
      consistency of domain CSs ranged from 0.48 to 0.95, and were above 0.60 for six
      domains. The 7 day test-retest reliability was acceptable as evidenced by high
      Pearson correlation coefficients (0.75-0.92, p < 0.01) for 6 of 7 domain CSs.
      Correlation coefficients between the seven domain CSs ranged from 0.007 to 0.390
      (p < 0.05 or 0.01 two-sided), indicating strong discriminant validity. The
      correlation coefficient between the alcohol dependence composite score of ASI-C-5
      and the Alcohol Use Disorders Identification Test (AUDIT) was 0.69 (p < 0.01),
      indicating good criterion validity. The frequency of extreme scores was low,
      except for significant floor effects in the "Drugs" and "Legal Status" domains.
      Collectively, these findings suggest that the ASI-C-5 exhibited strong
      reliability, validity, and responsiveness in Chinese male alcohol-dependent
      inpatients.

PMID- 23146315
TI  - Pregnancy loss and anxiety and depression during subsequent pregnancies: data
      from the C-ABC study.
AB  - OBJECTIVE: Previous studies have shown that pregnancy loss may affect the mental
      health of women in subsequent pregnancies. The China Anhui Birth Defects and
      Child Development cohort study therefore aimed to investigate the influence of
      pregnancy loss on anxiety and depression in subsequent pregnancies. STUDY DESIGN:
      In total, 20,308 pregnant women provided written informed consent and completed
      the study questionnaire. The Self-rating Anxiety Scale and Center for
      Epidemiologic Studies-Depression Scale were used to evaluate anxiety and
      depression in pregnant women. Pearson's chi(2) test and binary logistic
      regression were used for statistical analyses. RESULTS: Of 20,308 pregnant women,
      1495 (7.36%) had a history of miscarriage and 7686 (37.85%) had a history of
      induced abortion. The binary logistic regression model found that pregnant women
      with a history of miscarriage had a significantly higher risk of anxiety and
      depression in the first trimester than primigravidae after stratified analysis
      according to the timing of the first prenatal visit (p<0.05). Compared with
      pregnant women with no history of miscarriage, women who had a history of
      miscarriage and an interpregnancy interval of less than 6 months had increased
      risk of anxiety symptoms (p<0.05) and depression symptoms (p<0.05) during the
      first trimester. Women with an interpregnancy interval of 7-12 months had a 2.511
      fold higher risk of depression (p<0.05) than women with no history of
      miscarriage. These findings were not changed after adjustment for maternal age,
      maternal education, family income, place of residence and pre-pregnancy body mass
      index. CONCLUSIONS: Women with a history of miscarriage experienced significant
      anxiety and depression during their next pregnancy. A short interpregnancy
      interval and the first trimester are risk factors for adverse mental health.

PMID- 23146316
TI  - Ak(1) genetic polymorphism and season of conception.
AB  - OBJECTIVE: The season of conception affects human reproduction, intrauterine
      growth, neonatal parameters, sex ratio, cognitive development and, in adult life,
      performance in many fields. Associations between polymorphic enzymes and season
      of conception have been also reported. In this study we searched for a possible
      association between season of conception and adenylate kinase locus 1 (Ak(1)).
      STUDY DESIGN: Two samples of 381 and 248 consecutively newborn infants from two
      Italian cities with different geographical positions and climatic conditions were
      considered. Three way contingency table analysis and Student t-test analysis were
      performed. RESULTS: Ak(1)2-1 phenotype is more frequent in males conceived in the
      summer-autumn period than in those conceived in winter-spring and this
      association depends on maternal Ak(1) phenotype (p=0.001). There is also an
      interaction between season of conception and Ak(1) phenotype concerning their
      effects on sex ratio and birth weight. CONCLUSION: The present data suggest a
      complex interaction involving seasonal cycles, maternal and foetal Ak(1) genotype
      and sex of foetus concerning their effects on intrauterine selection and neonatal
      parameters.

PMID- 23146317
TI  - Adaptive margin radiotherapy for patients with prostate carcinoma: what's the
      benefit?
AB  - With daily portal images and repeated CT scans from 20 patients with gold markers
      (GM) an adaptive margin radiotherapy strategy (AMRT) was simulated and compared
      to traditional bony anatomy (BA) and standard GM verification protocols. AMRT is
      comparable with BA. GM protocols are superior.

PMID- 23146318
TI  - Bone marrow transplantation rescues intestinal mucosa after whole body radiation
      via paracrine mechanisms.
AB  - PURPOSE: Our previous study reveals bone marrow transplantation (BMT) recruits
      host marrow-derived myelomonocytic cells to radiation-injured intestine,
      enhancing stromal proliferation, leading secondarily to epithelial regeneration.
      In this study, we propose BMT ameliorates intestinal damage via paracrine
      mechanisms. MATERIALS AND METHODS: Angiogenic cytokines within the intestinal
      mucosa of mice after whole body irradiation (WBI) with or without BMT were
      measured by cytokine array and ELISA. BM conditioned medium (BMCM) with or
      without treatment with neutralizing antibodies to angiogenic cytokines were
      continuously infused into mice for three days after radiation. Carrageenan was
      used to deplete myelomonocytic cells of mice. RESULTS: BMT increased VEGF, bFGF
      and other angiogenic and chemotactic cytokines in the intestinal mucosa within
      24h after WBI. Infusion of BMCM ameliorated radiation-induced intestinal damage
      with improved stromal activity and prolonged survival of mice. Neutralization of
      bFGF, PDGF and other angiogenic cytokines within BMCM abolished the mitigating
      effect to the intestine. Pretreatment of carrageenan to recipient mice reversed
      some of the cytokine levels, including VEGF, bFGF and IGF within the intestinal
      mucosa after BMT. CONCLUSIONS: Our result suggests BMT recruits host
      myelomonocytic cells and enhances intestinal stroma proliferation after radiation
      by secreting cytokines enhancing angiogenesis and chemotaxis. Host myelomonocytic
      cells further uplift the paracrine effect to enhance intestinal mucosal recovery.

PMID- 23146319
TI  - A case study using the United Republic of Tanzania: costing nationwide HPV
      vaccine delivery using the WHO Cervical Cancer Prevention and Control Costing
      Tool.
AB  - BACKGROUND: The purpose, methods, data sources and assumptions behind the World
      Health Organization (WHO) Cervical Cancer Prevention and Control Costing (C4P)
      tool that was developed to assist low- and middle-income countries (LMICs) with
      planning and costing their nationwide human papillomavirus (HPV) vaccination
      program are presented. Tanzania is presented as a case study where the WHO C4P
      tool was used to cost and plan the roll-out of HPV vaccines nationwide as part of
      the national comprehensive cervical cancer prevention and control strategy.
      METHODS: The WHO C4P tool focuses on estimating the incremental costs to the
      health system of vaccinating adolescent girls through school-, health facility-
      and/or outreach-based strategies. No costs to the user (school girls, parents or
      caregivers) are included. Both financial (or costs to the Ministry of Health) and
      economic costs are estimated. The cost components for service delivery include
      training, vaccination (health personnel time and transport, stationery for tally
      sheets and vaccination cards, and so on), social mobilization/IEC (information,
      education and communication), supervision, and monitoring and evaluation (M&E).
      The costs of all the resources used for HPV vaccination are totaled and shown
      with and without the estimated cost of the vaccine. The total cost is also
      divided by the number of doses administered and number of fully immunized girls
      (FIGs) to estimate the cost per dose and cost per FIG. RESULTS: Over five years
      (2011 to 2015), the cost of establishing an HPV vaccine program that delivers
      three doses of vaccine to girls at schools via phased national introduction
      (three regions in year 1, ten regions in year 2 and all 26 regions in years 3 to
      5) in Tanzania is estimated to be US$9.2 million (excluding vaccine costs) and
      US$31.5 million (with vaccine) assuming a vaccine price of US$5 (GAVI 2011,
      formerly the Global Alliance for Vaccines and Immunizations). This is equivalent
      to a financial cost of US$5.77 per FIG, excluding the vaccine cost. The most
      important costs of service delivery are social mobilization/IEC and service
      delivery operational costs. CONCLUSIONS: When countries expand their immunization
      schedules with new vaccines such as the HPV vaccine, they face initial costs to
      fund critical pre-introduction activities, as well as incremental system costs to
      deliver the vaccines on an ongoing basis. In anticipation, governments need to
      plan ahead for non-vaccine costs so they will be financed adequately. Existing
      human resources need to be re-allocated or new staff need to be recruited for the
      program to be implemented successfully in a sustainable and long-term
      manner.Reaching a target group not routinely served by national immunization
      programs previously with three doses of vaccine requires new delivery strategies,
      more transport of vaccines and health workers and more intensive IEC activities
      leading to new delivery costs for the immunization program that are greater than
      the costs incurred when a new infant vaccine is added to the existing infant
      immunization schedule. The WHO C4P tool is intended to help LMICs to plan ahead
      and estimate the programmatic and operational costs of HPV vaccination.

PMID- 23146320
TI  - Endothelin antagonists in subarachnoid hemorrhage: what next?
AB  - In the previous issue of Critical Care, Ma and colleagues perform a meta-analysis
      of five randomized, clinical trials of endothelin antagonists in patients with
      aneurysmal subarachnoid hemorrhage. There are four trials using clazosentan and
      one trial with TAK-044. These studies show that endothelin plays an important
      role in the genesis of angiographic vasospasm. The benefit of these drugs is less
      on delayed cerebral ischemia and nonexistent on overall clinical outcome. Why the
      drugs reduce vasospasm but do not improve outcome could be because of side
      effects such as hypotension and pulmonary complications that are more common in
      patients treated with endothelin antagonists or because rescue therapy, which is
      used more in the placebo groups, improves outcome in these patients to the same
      extent as the endothelin antagonists. As the authors conclude, future studies of
      these drugs will need to consider these and other factors in their design. 

PMID- 23146321
TI  - Effects of aging-related losses in strength on the ability to recover from a
      backward balance loss.
AB  - Although muscle weakness is a risk factor for falls, its direct influence on the
      ability to prevent a fall is largely unknown. This study therefore investigated
      the effect of aging-related losses in strength on the ability to restore static
      balance following a recovery step from a backward balance loss. A six-link,
      sagittal-plane musculoskeletal model with 10 Hill-type musculotendon actuators
      was developed to simulate the strength characteristics and balance recovery
      motions of young and older adults. Using this model, feasible regions for balance
      recovery were mapped for each age group for "slow" and "fast" initial conditions
      of backward and downward velocity. For both conditions, there was considerable
      overlap between the feasible regions of young and older adults, with both age
      groups able to restore static balance from similar initial hip heights. However,
      the ranges of initial center of mass positions, relative to the rear heel, for
      which balance could be restored did not extend as far anteriorly or posteriorly
      for older adults. The feasible region did not extend as far upward, downward, or
      posteriorly for the "fast" condition, with these differences between conditions
      being similar in each age group. The results suggest that aging-related losses in
      strength impair the ability to recover from a backward balance loss only if older
      adults take a very short or very long recovery step behind the center of mass,
      even for high velocities at step touchdown. Training of the stepping response
      might therefore be more effective than strength training in preventing backward
      falls.

PMID- 23146322
TI  - Toe-in gait reduces the first peak knee adduction moment in patients with medial
      compartment knee osteoarthritis.
AB  - The first peak of the knee adduction moment has been linked to the presence,
      severity, and progression of medial compartment knee osteoarthritis. The
      objective of this study was to evaluate toe-in gait (decreased foot progression
      angle from baseline through internal foot rotation) as a means to reduce the
      first peak of the knee adduction moment in subjects with medial compartment knee
      osteoarthritis. Additionally, we examined whether the first peak in the knee
      adduction moment would cause a concomitant increase in the peak external knee
      flexion moment, which can eliminate reductions in the medial compartment force
      that result from lowering the knee adduction moment. We tested the following
      hypotheses: (a) toe-in gait reduces the first peak of the knee adduction moment,
      and (b) toe-in gait does not increase the peak external knee flexion moment.
      Twelve patients with medial compartment knee osteoarthritis first performed
      baseline walking trials and then toe-in gait trials at their self-selected speed
      on an instrumented treadmill in a motion capture laboratory. Subjects altered
      their foot progression angle from baseline to toe-in gait by an average of 5
      degrees  (p<0.01), which reduced the first peak of the knee adduction moment by
      an average of 13% (p<0.01). Toe-in gait did not increase the peak external knee
      flexion moment (p=0.85). The reduced knee adduction moment was accompanied by a
      medially-shifted knee joint center and a laterally-shifted center of pressure
      during early stance. These results suggest that toe-in gait may be a promising
      non-surgical treatment for patients with medial compartment knee osteoarthritis.

PMID- 23146323
TI  - The modelling of blood coagulation using the quartz crystal microbalance.
AB  - Blood is a clinically-important analytical matrix that is routinely selected for
      disease monitoring. Having a clear understanding of the mechanisms involved in
      blood coagulation is a key consideration in haemostasis, with modern clinical
      practices requiring rapid, miniaturised and informative diagnostic platforms to
      reliably study changes in viscoelasticity (VE). Oscillatory transducers such as
      the Quartz Crystal Microbalance (QCM) have considerable potential in this area,
      provided that they present simple, linear rheometric readings which can be
      adequately analysed and interpreted. Hence, integrating QCM data obtained in the
      laboratory with mathematical modelling of acoustic interactions between quartz
      crystal surfaces and coagulating blood is an important consideration for
      modelling thrombus formation. Here, we provide a comprehensive overview of
      experimental and theoretical applications currently being employed to monitor and
      model the VE properties of coagulating blood when applied to a QCM resonator,
      with key emphasis on data modelling and interpretation.

PMID- 23146324
TI  - [Prophylactic prescription of vitamin D in France: national multicenter
      epidemiological study of 3240 children under 6 years of age].
AB  - AIMS: The aim of the study was to assess compliance with the current
      recommendations of prophylactic prescription of vitamin D via a multicentric
      cross-sectional epidemiological survey of 3240 children under 6 years of age.
      METHOD: Parent questionnaires and data from the health records of children
      presenting to the emergency departments of 25 teaching hospitals and hospital
      centers provided information on the children's characteristics, their
      prescriptions, and other vitamin D intake. Based on the currently applicable
      recommendations, intakes of 600-1,200 IU/day - 900-1500 IU/day for children with
      pigmented skin and/or premature and/or hypotrophic children - are considered
      adequate. RESULTS: In 1606 infants, 9.8% of the prescriptions were below and
      23.7% were above the recommendations; in 1256 children between 18 months and 5
      years of age, 53.4% of the prescriptions were below and 5.1% were above the
      recommendations. Children at risk, those from the southern half of France, and
      those between 18 months and 5 years of age were more likely to receive a
      prescription below the recommendations; their risk of receiving a prescription
      above the recommended guidelines was smaller. Of the children aged between 61 and
      71 months, 85% had not received any prescription at all during the previous 12
      months. These results were compared with the laboratory data collected from a
      subsample of children. There was a significant correlation between the adequacy
      of the prescription and the biological vitamin D status both for 25
      hydroxyvitamin D (25-OH-D) serological concentrations and for calciuria.
      CONCLUSIONS: Only 66.6% of the prescriptions in children between 0 and 18 months
      of age and 41.5% in children between 19 months and 5 years of age comply with the
      recommendations; 53.4% of the prescriptions in the latter age group are below the
      current recommendations.

PMID- 23146325
TI  - A case report and literature review of "Chiclero's ulcer".
AB  - An 86-year-old man with history of travel to Guatemala presented with a 4-month
      history of an enlarging ulcerative lesion on his right ear. After several weeks
      of empiric treatment for otitis externa, histopathology, culture, and PCR
      analysis of a biopsy specimen confirmed the diagnosis of localized cutaneous
      leishmaniasis secondary to Leishmania mexicana. Known as "Chiclero's ulcer" in
      southeast Mexico and Latin America, this unique presentation of cutaneous
      leishmaniasis is caused mainly by the L. mexicana complex. Infection results in a
      single ulcerative lesion, most commonly involving the ear pinna, without a
      tendency for cutaneous metastasis, lymphatic or mucosal involvement. The majority
      of cases of "Chiclero's ulcer" spontaneously re-epithelialize without treatment
      within 3-9 months. This patient's lesion completely resolved without therapy
      after 11 months. "Chiclero's ulcer" should be considered in the differential
      diagnosis of a patient presenting with a chronic ulcerative lesion and history of
      travel to an endemic area.

PMID- 23146326
TI  - Can psychotherapists function as their own controls? Meta-analysis of the crossed
      therapist design in comparative psychotherapy trials.
AB  - OBJECTIVE: Clinical trials sometimes have the same therapists deliver more than 1
      psychotherapy, ostensibly to control for therapist effects. This "crossed
      therapist" design makes controlling for therapist allegiance imperative, as
      therapists may prefer one treatment they deliver to the other(s). Research has
      established a strong relationship between principal investigators' allegiances
      and treatment outcome. Study therapists' allegiances probably also influence
      outcome, yet this moderating factor on outcome has never been studied. DATA
      SOURCES: English language abstracts in PsycINFO and MEDLINE from January 1985 to
      December 2011 were searched for keywords psychotherapy and randomized trial.
      STUDY SELECTION: The search yielded 990 abstracts that were searched manually.
      Trials using the same therapists in more than 1 condition were included. DATA
      EXTRACTION: Thirty-nine studies fulfilled inclusion criteria. Meta-regression
      analyses assessed the influence of researchers' allegiance on treatment outcome,
      testing the hypothesis that studies poorly controlling for therapist allegiance
      would show stronger influence of researcher allegiance on outcome. A single-item
      measure assessed researchers' reported attempts to control for therapist
      allegiance. RESULTS: Only 1 of 39 studies (3%) measured therapist treatment
      allegiance. Another 5 (13%) mentioned controlling for, without formally
      assessing, therapist allegiance. Most publications (67%) did not even mention
      therapist allegiance. In studies not controlling for therapist allegiance,
      researcher allegiance strongly influenced outcome, whereas studies reporting
      control for therapist allegiance showed no differential researcher allegiance.
      Researchers with cognitive-behavioral therapy allegiance described controlling
      for therapist allegiance less frequently than other researchers. CONCLUSIONS: The
      crossed therapist design is subject to bias due to differential psychotherapist
      allegiance. Worrisome results suggest that researchers strongly allied to a
      treatment may ignore therapist allegiance, potentially skewing outcomes. All
      clinical trials, and especially crossed therapist designs, should measure
      psychotherapist allegiance to evaluate this possible bias.

PMID- 23146327
TI  - Recent incidence of type 1 diabetes mellitus in children 0-14 years in
      Newfoundland and Labrador, Canada climbs to over 45/100,000: a retrospective time
      trend study.
AB  - BACKGROUND: To study and update the provincial incidence of type 1 diabetes
      mellitus (T1DM) in Newfoundland and Labrador (NL), a province of Canada with a
      very high incidence previously reported in 2006, and one of the highest
      incidences reported worldwide. This is a retrospective time trend study of the
      incidence of T1DM, in children aged 0-14 years from 1987-2010 inclusive.
      FINDINGS: Over the study period 931 children aged 0-14 years were diagnosed with
      T1DM. The incidence of T1DM in this population over the period 1987 - 2010
      inclusive was 37.7 per 100,000 per year (95% CI 35. 3, 40.2)The incidence from
      2007-2010 was 49.9 per 100,000 per year (95% CI 42.2, 57.6). The incidence over
      this 24 year period increased by a factor of 1.03 per 100,000 per year.
      CONCLUSION: NL has one of the highest incidences of T1DM reported worldwide.
      Potential reasons for the very high incidence could be related to the unique
      genetic background of the population, northern latitude and vitamin D
      insufficiency, low breastfeeding rates, and high rates of cesarean section.

PMID- 23146328
TI  - Intranasal oxytocin increases covert attention to positive social cues.
AB  - BACKGROUND: The neuropeptide oxytocin (OT) has positive effects on the processing
      of emotional stimuli such as facial expressions. To date, research has focused
      primarily on conditions of overt visual attention. METHOD: We investigated
      whether a single intranasal dose of OT (24 IU) would modulate the allocation of
      attentional resources towards positive and negative facial expressions using a
      dot-probe paradigm in a sample of 69 healthy men. Attentional capacity for these
      facial cues was limited by presentation time (100 or 500 ms). In addition, we
      controlled for overt visual attention by recording eye movements using a remote
      eye tracker. RESULTS: Reaction times (RTs) in the dot-probe paradigm revealed a
      pronounced shift of attention towards happy facial expressions presented for 100
      ms after OT administration, whereas there were no OT-induced effects for longer
      presentation times (500 ms). The results could not be attributed to modulations
      of overt visual attention as no substance effects on gazes towards the facial
      target were observed. CONCLUSIONS: The results suggest that OT increased covert
      attention to happy faces, thereby supporting the hypothesis that OT modulates
      early attentional processes that might promote prosocial behavior.

PMID- 23146329
TI  - Preliminary evidence of different selection pressures on cancer cells as compared
      to normal tissues.
AB  - BACKGROUND: Cancer is characterized by both a high mutation rate as well as high
      rates of cell division and cell death. We postulate that these conditions will
      result in the eventual mutational inactivation of genes not essential to the
      survival of the cancer cell, while mutations in essential genes will be
      eliminated by natural selection leaving molecular signatures of selection in
      genes required for survival and reproduction. By looking for signatures of
      natural selection in the genomes of cancer cells, it should therefore be possible
      to determine which genes have been essential for the development of a particular
      cancer. METHODS: We provide a proof of principle test of this idea by applying a
      test of neutrality (Nei-Gojobori Z-test of selection) to 139 cancer-related
      nucleotide sequences obtained from GenBank representing 46 cancer-derived genes.
      RESULTS: Among cancer associated sequences, 10 genes showed molecular evidence of
      selection. Of these 10 genes, four showed molecular evidence of selection in non
      cancer transcripts. Among non-cancer associated sequences, eight genes showed
      molecular evidence of selection, with four of these also showing selection in the
      cancer associated sequences. CONCLUSIONS: These results provide preliminary
      evidence that the same genes may experience different selection pressures within
      normal and cancer tissues. Application of this technique could identify genes
      under unique selection pressure in cancer tissues and thereby indicate possible
      targets for therapeutic intervention.

PMID- 23146330
TI  - Image cytometry: protocols for 2D and 3D quantification in microscopic images.
AB  - Microscopy-based imaging is booming and the need for tools to retrieve
      quantitative data from images is urgent. This book provides simple but reliable
      tools to generate valid quantitative gene expression data, at the mRNA, protein
      and activity level, from microscopic images in relation to structures in cells,
      tissues and organs in 2D and 3D. Volumes, areas, lengths and numbers of cells and
      tissues can be calculated and related to these gene expression data while
      preserving the 2D and 3D morphology. Image cytometry thus provides a
      comprehensive toolkit to study molecular processes and structural changes at the
      level of cells and tissues.

PMID- 23146331
TI  - Oral health-related quality of life and satisfaction before and after treatment
      with complete dentures in a Dental School in Brazil.
AB  - PURPOSE: The aim of this study was to evaluate the impact of treatment with new
      complete dentures on oral health-related quality of life and satisfaction of
      edentulous patients attending the Prosthodontic Department in a Dental School in
      Brazil. METHODS: A total of 70 edentulous subjects (37-86 years) treated by
      undergradute students at the Aracatuba Dental School, University of State of Sao
      Paulo, were accessed. A specific questionnaire for edentulous patients (EDENT)
      based on the Oral Health Impact Profile (OHIP-EDENT) was applied to collect
      information on patient oral health-related quality of life. Questions related to
      the personal satisfaction of the edentulous patients with their complete dentures
      were also included. The patients were accessed before the treatment, and 3 months
      after receiving the new dentures. RESULTS: After rehabilitation with new complete
      dentures, all domains of OHIP-EDENT showed significant improvements. There was
      also a significant improvement in patient satisfaction after placement of new
      complete dentures. Furthermore, it was possible to observe association between
      upper denture satisfaction and age. CONCLUSION: Conventional complete dentures
      may have a positive impact on oral health-related quality of life and
      satisfaction of edentulous patients.

PMID- 23146333
TI  - Parenteral omega-3 fatty acids: pouring oil on troubled waters?
AB  - A meta-analysis of parenteral fish oil in 23 studies in intensive care unit (ICU)
      and non-ICU patients reported a reduced infection rate (significant in ICU
      patients) and shorter lengths of ICU and hospital stays (both non-ICU and ICU
      patients). Parenteral fish oil reduced inflammation and improved oxygenation
      index and liver function. The findings of the meta-analysis are discussed in this
      report. 

PMID- 23146334
TI  - Evaluating the impact of demand-side management on water resources under changing
      climatic conditions and increasing population.
AB  - This study investigated the effect of increasing population and changing climatic
      conditions on the water resources of a semi-arid region, the Las Vegas Valley
      (LVV) in southern Nevada. A system dynamics model was developed for the LVV from
      1989 to 2035. The impact of climate change on water demand and the water supply
      from the Colorado River was modeled, using projections from 16 global climate
      models for 3 emission scenarios. Variability in water demand and supply under
      different scenarios of population growth and demand management, including water
      conservation and water pricing, was evaluated. With the population growth that
      was projected, if no further demand management policies were implemented, the LVV
      would not be able to meet the water demand in the near future. However, by
      combining water conservation and pricing policies, the available supply could
      last well into the future. The reduction in water demand in 2035 was predicted to
      be 327 million cubic meters (MCM) for 'status quo' population growth, or 30.6%;
      408 MCM for 50% of the projected growth, or 38%; and 511 MCM for no population
      growth, or 47.8%. Water supply reliability decreased significantly with changing
      climatic conditions. Therefore, major challenges to water sustainability in the
      LVV would be due to rapid population growth as well as to climate variability.
      However, with the combination of reduced population growth rate and water
      conservation policies, the Colorado River supply could meet the future demand of
      the LVV most of the time.

PMID- 23146332
TI  - Parenting-related stress and psychological distress in mothers of toddlers with
      autism spectrum disorders.
AB  - BACKGROUND: Parents of children with autism spectrum disorders (ASDs) are at risk
      for higher stress levels than parents of children with other developmental
      disabilities and typical development. Recent advances in early diagnosis have
      resulted in younger children being diagnosed with ASDs but factors associated
      with parent stress in this age group are not well understood. AIMS: The present
      study examined parenting-related stress and psychological distress in mothers of
      toddlers with ASD, developmental delay without ASD (DD), and typical development.
      The impact of child problem behavior and daily living skills on parenting-stress
      and psychological distress were further investigated. METHODS: Participants were
      part of a larger research study on early ASD intervention. RESULTS: Parent self
      report of parenting-related stress and psychological distress was utilized.
      Parents of toddlers with ASD demonstrated increased parenting-related stress
      compared with parents of toddlers with DD and typical development. However,
      psychological distress did not differ significantly between the groups. Child
      behavior problems, but not daily living skills emerged as a significant predictor
      of parenting-related stress and psychological distress. This was true for both
      mothers of children with ASD and DD. CONCLUSIONS: These finding suggest that
      parents' abilities to manage and reduce behavior problems is a critical target
      for interventions for young children with ASD and DD in order to improve child
      functioning and decrease parenting-related stress.

PMID- 23146335
TI  - Arsenic removal by modified activated carbons with iron hydro(oxide)
      nanoparticles.
AB  - Different activated carbons modified with iron hydro(oxide) nanoparticles were
      tested for their ability to adsorb arsenic from water. Adsorption isotherms were
      determined at As (V) concentrations < 1 ppm, with varying pH (6, 7, 8) and
      temperature (25 and 35  degrees C). Also, competition effect of anions on the As
      (V) adsorption capacity was evaluated using groundwater. The surface areas of the
      modified activated carbons ranged from 632 m(2) g(-1) to 1101 m(2) g(-1), and
      their maximum arsenic adsorption capacity varied from 370 MUg g(-1) to 1250 MUg
      g(-1). Temperature had no significant effect on arsenic adsorption; however,
      arsenic adsorption decreased 32% when the solution pH increased from 6 to 8. In
      addition, when groundwater was used in the experiments, the arsenic adsorption
      considerably decreased due to the presence of competing anions (mainly SO(4)(2-),
      Cl(-) and F(-)) for active sites. The data from kinetic studies fitted well to
      the pseudo-second-order model (r(2) = 0.98-0.99). The results indicated that
      sample CAZ-M had faster kinetics than the other two materials in the first 10
      min. However, sample F400-M was only 5.5% slower than CAZ-M. The results of this
      study show that iron modified activated carbons are efficient adsorbents for
      arsenic at concentrations lower than 300 MUg L(-1).

PMID- 23146336
TI  - Angiogenesis following cell injection is induced by an excess inflammatory
      response coordinated by bone marrow cells.
AB  - The aim of this study was to identify novel angiogenic mechanisms underlying the
      regenerative process. To that end, interactions between adipose tissue-derived
      stromal cells (ASCs) and bone marrow cells (BMCs) were initially investigated
      using real-time fluorescence optical imaging. To monitor cell behavior in mice,
      we injected green fluorescent protein-positive (GFP(+)) BMCs into the tail vein
      and injected PKH26-labeled ASCs behind the ears. Angiogenesis and inflammation
      were observed at these sites via an optical imaging probe. Injected GFP(+) BMCs
      migrated from the blood vessels into the tissues surrounding the ASC injection
      sites. Many of the migrating GFP(+) BMCs discovered at the ASC injection sites
      were inflammatory cells, including Gr-1(+), CD11b(+), and F4/80(+) cells. ASCs
      cocultured with inflammatory cells secreted increased levels of chemokines such
      as macrophage inflammatory protein (MIP)-1alpha, MIP-1beta, keratinocyte-derived
      chemokines, and monocyte chemotactic protein 1. Similarly, these ASCs secreted
      increased levels of angiogenic growth factors such as hepatocyte growth factor
      and vascular endothelial growth factor. However, when anti-CXC chemokine receptor
      type 4 antibody was injected at regular intervals, the migration of GFP(+) BMCs
      (especially Gr-1(+) and CD11b(+) cells) to ASC injection sites was inhibited, as
      was angiogenesis. The collective influence of the injected ASCs and BMC-derived
      inflammatory cells promoted acute inflammation and angiogenesis. Together, the
      results suggest that the outcome of cell-based angiogenic therapy is influenced
      not only by the injected cells but also by the effect of intrinsic inflammatory
      cells. 

PMID- 23146337
TI  - Inflammation and biomarkers in vascular disease: emerging insights and
      opportunities.

PMID- 23146338
TI  - Isoform separation and binding site determination of mono-PEGylated lysozyme with
      pH gradient chromatography.
AB  - Covalent attachment of PEG to proteins, known as PEGylation, is currently one of
      the main approaches for improving the pharmacokinetics of biopharmaceuticals.
      However, the separation and characterization especially of positional isoforms of
      PEGylated proteins are still challenging tasks. A common purification strategy
      uses ion exchange chromatography with increasing ionic strength by shallow salt
      gradients. This paper presents a method which applies a linear pH gradient
      chromatography to separate five of six possible isoforms of mono-PEGylated
      lysozyme, modified with 5 kDa and 10 kDa mPEG-aldehyde. To identify the
      corresponding PEGylation sites a comparison of elution pH values and calculated
      isoelectric points of each isoform, was used. The resulting correlation showed an
      R(2)>0.99. Fractionation, tryptic digestion and subsequent MALDI-MS analysis of
      each peak, verified the predicted elution order. Based on UV areas the N-terminal
      amine at lysine 1 exhibited the highest reactivity, followed by the lysine 33
      residue.

PMID- 23146339
TI  - The effect of age on first-line chemotherapy for epithelial ovarian cancer and
      primary peritoneal carcinoma.

PMID- 23146341
TI  - Optimal number of samples to test for institutional respiratory infection
      outbreaks in Ontario.
AB  - The objective of this study was to determine the optimal number of respiratory
      samples per outbreak to be tested for institutional respiratory outbreaks in
      Ontario. We reviewed respiratory samples tested for respiratory viruses by
      multiplex PCR as part of outbreak investigations. We documented outbreaks that
      were positive for any respiratory viruses and for influenza alone. At least one
      virus was detected in 1454 (85?2%) outbreaks. The ability to detect influenza or
      any respiratory virus increased as the number of samples tested increased. When
      analysed by chronological order of when samples were received at the laboratory,
      percent positivity of outbreaks testing positive for any respiratory virus
      including influenza increased with the number of samples tested up to the ninth
      sample, with minimal benefit beyond the fourth sample tested. Testing up to four
      respiratory samples per outbreak was sufficient to detect viral organisms and
      resulted in significant savings for outbreak investigations.

PMID- 23146340
TI  - Evidence for genetic differentiation at the microgeographic scale in Phlebotomus
      papatasi populations from Sudan.
AB  - BACKGROUND: Cutaneous Leishmaniasis (CL) is endemic in Sudan. It is caused by
      Leishmania major parasites and transmitted by Phlebotomus papatasi sandflies.
      Recently, uncommon clinical manifestations of CL have been reported. Moreover, L.
      donovani parasites that cause Visceral Leishmaniasis (VL) have been isolated from
      CL lesions of some patients who contracted the disease in Khartoum State, Central
      Sudan with no history of travelling to VL endemic sites on south-eastern Sudan.
      Because different clinical manifestations and the parasite behaviour could be
      related to genetic differentiation, or even sub-structuring within sandfly vector
      populations, a population genetic study was conducted on P. papatasi populations
      collected from different localities in Khartoum State known for their uncommon CL
      cases and characterized by contrasting environmental conditions. METHODS: A set
      of seven microsatellite loci was used to investigate the population structure of
      P. papatasi samples collected from different localities in Khartoum State,
      Central Sudan. Populations from Kassala State, Eastern Sudan and Egypt were also
      included in the analyses as outgroups. The level of genetic diversity and genetic
      differentiation among natural populations of P. papatasi was determined using FST
      statistics and Bayesian assignments. RESULTS: Genetic analyses revealed
      significant genetic differentiation (FST) between the Sudanese and the Egyptian
      populations. Within the Sudanese P. papatasi populations, one population from
      Gerif West, Khartoum State, exhibited significant genetic differentiation from
      all other populations including those collected as near as 22 km. CONCLUSION: The
      significant genetic differentiation of Gerif West P. papatasi population from
      other Sudanese populations may have important implication for the epidemiology of
      leishmaniasis in Khartoum State and needs to be further investigated. Primarily,
      it could be linked to the unique location of Gerif West which is confined by the
      River Nile and its tributaries that may act as a natural barrier for gene flow
      between this site and the other rural sites. The observed high migration rates
      and lack of genetic differentiation among the other P. papatasi populations could
      be attributed to the continuous human and cattle movement between these
      localities.

PMID- 23146342
TI  - Injuries in prepubertal and pubertal girls.
AB  - In this chapter, examination techniques are first recommended, and then
      terminology for genital injuries that may occur after child sexual abuse or rape
      (e.g. lacerations, notch, transaction) are described. Current evidence for these
      injuries is provided. Areas of controversy (e.g. hymenal diameter, hymenal width)
      are described and completed with cautionary notes on inflammation, bruising,
      abrasions, bumps and mounds, tags, labial fusion, lichen sclerosis). The chapter
      concludes with a debate on normal findings that are reported to occur in up to
      99% of children referred for examination.

PMID- 23146344
TI  - [Detection of micro-embolic signals: a review of the literature].
AB  - BACKGROUND: The detection of micro-embolic signals (MES), by transcranial Doppler
      sonography might be useful for risk stratification in patients with symptomatic
      and asymptomatic carotid or cerebral artery stenosis, dissections, aortic
      atheroma, interventional procedures, and right to left cardiac shunts. AIM:
      Review of the technique and clinical situations of MES detection. METHODS: PubMed
      search from 1990 to 2012. RESULTS: MES were found in 0,19, 48% versus 0,3, and
      12% of patients with symptomatic and asymptomatic inferior than 30, 30 to 69, and
      70 to 99% carotid stenosis, respectively. MES were related to the risk of
      recurrent stroke or transient ischemic attack (TIA). In the ACES study, the
      absolute annual risk of stroke or TIA after 2 years was 7% with vs 3% without
      MES. In patients with intracranial stenosis, the risk of stroke recurrence was
      48% with vs 7% without MES at 13.6 months follow-up. MES were reported in 25% of
      the symptomatic versus none of the asymptomatic patients with intracranial
      stenosis. CONCLUSION: Detection of MES is feasible and reproducible for
      multicenter studies, using rigourous methodology and long lasting recordings. It
      may contribute to risk stratification, especially in patients with extra- or
      intracranial stenosis.

PMID- 23146345
TI  - Pudendal artery pseudoaneurysm after robot-assisted laparoscopic radical
      prostatectomy.
AB  - Pseudoaneurysms in urology, especially for pelvic surgeries, are rare. We report
      a patient who presented with late recurrent hematuria due to formation of an
      accessory pudendal artery pseudoaneurysm (Clavien grade III) after robot-assisted
      laparoscopic radical prostatectomy.

PMID- 23146346
TI  - An unusual case of S-shaped malformation of the ipsilateral kidney with normal
      contralateral kidney.
AB  - Crossed ectopia is a rare congenital anomaly. S-shaped (sigmoid) kidney is one of
      the varieties of crossed ectopia that is associated with absence of any renal
      tissue in the contralateral renal fossa. S-shaped malformation of an ipsilateral
      kidney with presence of the contralateral kidney is an extremely rare condition
      and, to our knowledge, has been described only once before in the literature. We
      present the case and discuss the hypothesis for this rare malformation.

PMID- 23146347
TI  - Assessment of the morphological features of degenerative mitral valve disease
      using 64-slice multi detector computed tomography.
AB  - BACKGROUND: Patients with severe mitral regurgitation may be screened for
      coronary artery disease with the use of cardiac computed tomography before valve
      surgery. OBJECTIVE: We hypothesized that dual-source multidetector computed
      tomography (DSCT) could effectively predict the culprit mitral valve scallop
      identified during surgery among patients with degenerative mitral valve disease
      undergoing surgical mitral valve repair. METHODS: Twenty-six patients (7 women)
      with known severe mitral regurgitation underwent elective mitral valve repair
      from September 2006 through December 2009 at our institution. An additional 10
      patients underwent aortic valve replacement and had no documented history of
      mitral valve disease. All patients underwent transthoracic echocardiography and
      had retrospectively gated DSCT performed to evaluate the coronary arteries before
      surgery. Each mitral scallop was identified as either normal, prolapsed, or
      flail. CT findings were compared with operative findings, which were guided by
      intraoperative transesophageal echocardiography (TEE). RESULTS: In the 26
      patients examined, DSCT identified flail in 23 scallops and prolapse in 48. DSCT
      agreed with operative findings on identification of the culprit scallop in 25 of
      26 patients. On a per-patient and per-scallop basis, the observed kappa statistic
      for agreement between DSCT and operative findings was 0.82. Of the 60 scallops in
      the aortic valve group, all were judged to be normal by both DSCT and TEE.
      CONCLUSIONS: In patients with degenerative mitral valve disease undergoing
      cardiac surgery, DSCT demonstrates excellent agreement with intraoperative
      findings. DSCT can be used to identify the affected mitral valve scallop and its
      structure in patients who are candidates for mitral valve repair.

PMID- 23146348
TI  - Is chronic levodopa therapy associated with distal symmetric polyneuropathy in
      Parkinson's disease?

PMID- 23146349
TI  - Protective effects of probiotic Lactobacillus casei Zhang against endotoxin- and
      d-galactosamine-induced liver injury in rats via anti-oxidative and anti
      inflammatory capacities.
AB  - Lactobacillus casei Zhang (LcZ) has been recently isolated from the traditional
      Mongolian beverage koumiss and has a set of favorable probiotic properties,
      including aciduricity, bile resistance and ability to colonize the
      gastrointestinal tract. We have previously reported the anti-oxidative properties
      of LcZ in the hyperlipidemic rats. In this study, the hepatoprotective effects of
      LcZ against lipopolysaccharide (LPS) and d-galactosamine (D-GalN)-induced liver
      injury were investigated. We found that pretreatment with LcZ significantly
      improved survival of rats challenged with LPS/D-GalN. In addition, pretreatment
      with LcZ significantly decreased alanine transaminase (ALT) and aspartate
      aminotransferase (AST) levels in LPS/D-GalN-challenged rats, which were
      accompanied by diminished liver injuries, reduced malondialdehyde (MDA) content
      and increased superoxide dismutase (SOD) activity in liver homogenates.
      Pretreatment with LcZ also markedly reduced LPS/D-GalN-induced production of
      hepatic nitric oxide (NO), activation of inducible nitric oxide synthase (iNOS)
      and expression of tumor necrosis factor-alpha (TNF-alpha). Furthermore, hepatic
      toll-like receptor 4 (TLR4) mRNA and protein levels, the phosphorylation of I
      kappaB and translocation of nuclear factor kappaB (NF-kappaB) were significantly
      down-regulated by pretreatment with LcZ. These results suggest that pretreatment
      with LcZ protects against LPS/D-GalN-induced liver injury in rats via its anti
      oxidative and anti-inflammatory capacities. The hepatoprotective effects of LcZ
      are associated with an inhibition of TLR4 expression and TLR4 signaling.

PMID- 23146350
TI  - Exploiting the noise: improving biomarkers with ensembles of data analysis
      methodologies.
AB  - BACKGROUND: The advent of personalized medicine requires robust, reproducible
      biomarkers that indicate which treatment will maximize therapeutic benefit while
      minimizing side effects and costs. Numerous molecular signatures have been
      developed over the past decade to fill this need, but their validation and up
      take into clinical settings has been poor. Here, we investigate the technical
      reasons underlying reported failures in biomarker validation for non-small cell
      lung cancer (NSCLC). METHODS: We evaluated two published prognostic multi-gene
      biomarkers for NSCLC in an independent 442-patient dataset. We then
      systematically assessed how technical factors influenced validation success.
      RESULTS: Both biomarkers validated successfully (biomarker #1: hazard ratio (HR)
      1.63, 95% confidence interval (CI) 1.21 to 2.19, P = 0.001; biomarker #2: HR
      1.42, 95% CI 1.03 to 1.96, P = 0.030). Further, despite being underpowered for
      stage-specific analyses, both biomarkers successfully stratified stage II
      patients and biomarker #1 also stratified stage IB patients. We then
      systematically evaluated reasons for reported validation failures and find they
      can be directly attributed to technical challenges in data analysis. By examining
      24 separate pre-processing techniques we show that minor alterations in pre
      processing can change a successful prognostic biomarker (HR 1.85, 95% CI 1.37 to
      2.50, P < 0.001) into one indistinguishable from random chance (HR 1.15, 95% CI
      0.86 to 1.54, P = 0.348). Finally, we develop a new method, based on ensembles of
      analysis methodologies, to exploit this technical variability to improve
      biomarker robustness and to provide an independent confidence metric.
      CONCLUSIONS: Biomarkers comprise a fundamental component of personalized
      medicine. We first validated two NSCLC prognostic biomarkers in an independent
      patient cohort. Power analyses demonstrate that even this large, 442-patient
      cohort is under-powered for stage-specific analyses. We then use these results to
      discover an unexpected sensitivity of validation to subtle data analysis
      decisions. Finally, we develop a novel algorithmic approach to exploit this
      sensitivity to improve biomarker robustness.

PMID- 23146352
TI  - Molecular confirmation of the occurrence in Germany of Anopheles daciae (Diptera,
      Culicidae).
AB  - BACKGROUND: Anopheles daciae, a newly described member of the Maculipennis group,
      was recently reported from western, southern and eastern Europe. Before its
      recognition, it had commonly been listed under the name of An. messeae, due to
      its extreme morphological and genetic similarities. As the sibling species of the
      Maculipennis group are known to differ in their vector competences for malaria
      parasites and other pathogens, the occurrence of An. daciae in a given region
      might have an impact on the epidemiology of mosquito-borne diseases. Mosquito
      collections from different localities in Germany were therefore screened for An.
      daciae. METHODS: Adult and immature Maculipennis group mosquitoes were collected
      between May 2011 and June 2012 at 23 different sites in eight federal states of
      Germany. A standard PCR assay was used to differentiate the previously known
      sibling species while the ITS2 rDNA of specimens preliminarily identified as An.
      messeae/daciae was sequenced and analysed for species-specific nucleotide
      differences. RESULTS: Four hundred and seventy-seven Anopheles specimens were
      successively identified to Maculipennis group level by morphology and to species
      level by DNA-based methods. Four species of the Maculipennis group were
      registered: An. messeae (n = 384), An. maculipennis (n = 82), An. daciae (n = 10)
      and An. atroparvus (n = 1). Anopheles daciae occurred at four sites in three
      federal states of Germany, three of the sites being located in north-eastern
      Germany (federal states of Brandenburg and Saxony) while one collection site was
      situated in the northern Upper Rhine Valley in the federal state of Hesse, south
      western Germany. CONCLUSIONS: The detection of An. daciae represents the first
      recognition of this species in Germany where it was found to occur in sympatry
      with An. messeae and An. maculipennis. As the collection sites were in both north
      eastern and south-western parts of Germany, the species is probably even more
      widely distributed in Germany than demonstrated, albeit apparently with low
      population densities. Research is needed that confirms the species status of An.
      daciae and elucidates its vector competence as compared to An. messeae and the
      other species of the Maculipennis group, in order to optimize management of
      possible future outbreaks of diseases caused by pathogen transmission through
      Maculipennis group mosquitoes.

PMID- 23146351
TI  - Combining neurotrophin-transduced schwann cells and rolipram to promote
      functional recovery from subacute spinal cord injury.
AB  - Following spinal cord injury (SCI), both an inhibitory environment and lack of
      intrinsic growth capacity impede axonal regeneration. In a previous study,
      prevention of cyclic adenosine monophosphate (AMP) hydrolysis by the
      phosphodiesterase-4 inhibitor rolipram, in combination with Schwann cell (SC)
      grafts, promoted significant supraspinal and proprioceptive fiber growth and/or
      sparing and improved locomotion. In another study, transplanted SCs transduced to
      generate a bifunctional neurotrophin (D15A) led to significant increases in graft
      SCs and axons, including supraspinal and myelinated axons. Here we studied the
      growth and myelination of local and supraspinal axons and functional outcome
      following the combination of rolipram administration and neurotrophin-transduced
      SC implantation after SCI. Rolipram was administered subcutaneously for 4 weeks
      immediately after contusion at vertebral T8 (25.0-mm weight drop, MASCIS
      impactor). GFP or GFP-D15A-transduced SCs were injected into the injury epicenter
      1 week after SCI. GFP-D15A SC grafts and GFP SC grafts with rolipram contained
      significantly more serotonergic fibers compared to GFP SCs. SC myelinated axons
      were increased significantly in GFP SC with rolipram-treated animals compared to
      animals receiving SCI alone. Rolipram administered with either GFP or GFP-D15A
      SCs significantly increased numbers of brain stem-derived axons below the
      lesion/implant area and improved hindlimb function. Compared to the single
      treatments, the combination led to the largest SC grafts, the highest numbers of
      serotonergic fibers in the grafts, and increased numbers of axons from the
      reticular formation below the lesion/implant area and provided the greatest
      improvement in hindlimb function. These findings demonstrate the therapeutic
      potential for a combination therapy involving the maintenance of cyclic AMP
      levels and neurotrophin-transduced SCs to repair the subacutely injured spinal
      cord. 

PMID- 23146353
TI  - Low-level processing deficits underlying poor contrast sensitivity for moving
      plaids in anisometropic amblyopia.
AB  - Many studies using random dot kinematograms have indicated a global motion
      processing deficit originated from extrastriate cortex, specifically middle
      temporal area (MT) and media superior temporal area (MST), in patients with
      amblyopia. However, the nature of this deficit remains unclear. To explore
      whether the ability of motion integration is impaired in amblyopia, contrast
      sensitivity for moving plaids and their corresponding component gratings were
      measured over a range of stimulus durations and spatial and temporal frequencies
      in 10 control subjects and 13 anisometropic amblyopes by using a motion direction
      discrimination task. The results indicated a significant loss of contrast
      sensitivity for moving plaids as well as for moving gratings at intermediate and
      high spatial frequencies in amblyopic eyes (AEs). Additionally, we found that the
      loss of contrast sensitivity for moving plaids was statistically equivalent to
      that for moving component gratings in AEs, that is, the former could be almost
      completely accounted for by the latter. These results suggest that the
      integration of motion information conveyed by component gratings of moving plaids
      may be intact in anisometropic amblyopia, and that the apparent deficits in
      contrast sensitivity for moving plaids in anisometropic amblyopia can be almost
      completely attributed to those for gratings, that is, low-level processing
      deficits.

PMID- 23146354
TI  - Phytotoxicity of multi-walled carbon nanotubes on red spinach (Amaranthus
      tricolor L) and the role of ascorbic acid as an antioxidant.
AB  - Carbon nanotubes (CNTs) are a novel nanomaterial with wide potential
      applications; however the adverse effects of CNTs following environmental
      exposure have recently received significant attention. Herein, we explore the
      systemic toxicity and potential influence of 0-1000 mg L(-1) the multi-walled
      CNTs on red spinach. The multi-walled CNTs exposed plants exhibited growth
      inhibition and cell death after 15 days of hydroponic culture. The multi-walled
      CNTs had adverse effects on root and leaf morphology, as observed by scanning
      electron microscopy (SEM) and transmission electron microscopy (TEM). Raman
      spectroscopy detected the multi-walled CNTs in leaves. Biomarkers of nanoparticle
      toxicity, reactive oxygen species (ROS), and cell damage in the red spinach were
      greatly increased 15 days post-exposure to the multi-walled CNTs. These effects
      were reversed when the multi-walled CNTs were supplemented with ascorbic acid
      (AsA), suggesting a role of ROS in the multi-walled CNT-induced toxicity and that
      the primary mechanism of the multi-walled CNTs' toxicity is oxidative stress.

PMID- 23146355
TI  - Nephelometric and functional parameters response of coagulation for the
      purification of industrial wastewater using Detarium microcarpum.
AB  - Turbidimetry was used to study the coagulation performance of Detarium
      microcarpum (DM) in a fibre cement effluent (FCE) at room temperature. Analysis
      of variance (ANOVA) and Duncan new multiple range test (DNMRT) statistics were
      used to determine statistical difference of the coagulation performance of DM at
      various dosages and varying FCE pH. Increasing the coagulant dosage from 100 mg/L
      to 500 mg/L had no significant difference on the coagulation performance of DM at
      the same pH, however, varying FCE pH between 4 and 12 using the same coagulant
      dosage, had significant difference on the coagulation performance of DM.

PMID- 23146356
TI  - The functional neural architecture of self-reports of affective experience.
AB  - BACKGROUND: The ability to self-report on affective experience is essential to
      both our everyday communication about emotion and our scientific understanding of
      it. However, the underlying cognitive and neural mechanisms for how people
      construct statements even as simple as "I feel bad!" remain unclear. We examined
      whether the neural architecture underlying the ability to make statements about
      affective experience is composed of distinct functional systems. METHODS: In a
      novel functional magnetic neuroimaging paradigm, 20 participants were shown
      images varying in affective intensity; they were required either to attend to and
      judge the affective response versus to nonaffective aspects of the stimulus and
      either to categorize their response into a verbal label or report on a scale that
      did not require verbal labeling. RESULTS: We found that the ability to report on
      affective states involves (at least) three separable systems, one for directing
      attention to the affective response and making attributions about it that
      involves the dorsomedial prefrontal cortex, one for categorizing the response
      into a verbal label or word that involves the ventrolateral prefrontal cortex,
      and one sensitive to the intensity of the affective response including the
      ventral anterior insula and amygdala. CONCLUSIONS: These results suggest that
      unified statements about affective experience rely on integrating information
      from several distinct neural systems. Results are discussed in the context of how
      disruptions to one or another of these systems may produce unique deficits in the
      ability to describe affective states and the implications this may hold for
      clinical populations.

PMID- 23146358
TI  - Intake of oxidised fish oil does not affect circulating levels of oxidised LDL or
      inflammatory markers in healthy subjects.

PMID- 23146357
TI  - Coverage of blood vessels by astrocytic endfeet is reduced in major depressive
      disorder.
AB  - BACKGROUND: Depression and cerebrovascular disease influence each other,
      according to clinical studies. Despite this evidence, no studies have
      investigated the relationship between major depressive disorder (MDD) and
      cerebrovascular disease at the cellular level. Astrocytic processes are a crucial
      interface between blood vessels and neurons, and astrocyte density is reduced in
      MDD. This study investigated the coverage of vessels by astrocyte endfeet in the
      prefrontal cortex in MDD. METHODS: Thirteen pairs of MDD and nonpsychiatric
      control subjects were used for double immunofluorescent staining and confocal
      image analysis. Frozen sections of gray matter from orbitofrontal area 47 and
      white matter from the ventromedial prefrontal cortex were examined. Astrocytic
      processes (labeled with antibodies for aquaporin-4 (AQP4) or glial fibrillary
      acidic protein were co-localized with blood vessels (labeled with an antibody to
      collagen IV) to measure the coverage of vessel walls by astrocyte processes.
      RESULTS: The coverage of blood vessels by endfeet of AQP4-immunoreactive (IR)
      astrocytes was significantly reduced by 50% in subjects with MDD as compared with
      control subjects [analysis of covariance: F(1,23) = 5.161, p = .033]. This
      difference was detected in orbitofrontal gray matter but not in white matter.
      Conversely, the coverage of vessels by glial fibrillary acidic protein-IR
      processes did not significantly differ between the groups. CONCLUSIONS: A
      significant reduction in the coverage of gray matter vessels by AQP4-IR astrocyte
      processes in MDD suggests alterations in AQP4 functions such as regulation of
      water homeostasis, blood flow, glucose transport and metabolism, the blood-brain
      barrier, glutamate turnover, and synaptic plasticity.

PMID- 23146359
TI  - Reading nutrition labels is associated with a lower risk of metabolic syndrome in
      Korean adults: the 2007-2008 Korean NHANES.
AB  - BACKGROUND AND AIMS: Several studies demonstrated that reading nutrition labels
      was associated with healthier food choices, despite some controversy. This study
      investigated the association between the use of nutrition labels and metabolic
      syndrome (MetS) in Korean adults. METHODS AND RESULTS: This cross-sectional study
      included 7756 individuals who participated in the 2007-2009 Korean National
      Health and Nutrition Examination Survey (KNHANES). A self-reported questionnaire
      was used to determine participant's awareness of nutrition labels. Modified Asian
      criteria based on a harmonizing definition of MetS were adopted. Individuals in
      the group that read nutrition labels (the Reading Group) were youngest and
      leanest, but their daily caloric intake fell between that of the group that did
      not read nutrition labels (the Non-Reading Group) and the group that did not know
      about them (the Not-Knowing Group). The prevalence of MetS was 16.8% in the
      Reading Group, 27.2% in the Non-Reading Group, and 47.3% in the Not-Knowing
      Group. In comparison to participants in the Reading Group, the odds ratios (95%
      confidence interval) for MetS in the participants in the Non-Reading Group and
      Not-Knowing Group were 1.85 (1.60-2.14) and 4.44 (3.79-5.20), respectively, when
      not adjusted. The relationship between the use of nutrition labels and MetS
      remained statistically significant even after adjusting for covariates such as
      age, sex and socioeconomic status including household income and education level
      [1.27 (1.05-1.53) in the Non-Reading Group and 1.34 (1.05-1.70) in the Not
      Knowing Group]. CONCLUSION: Reading nutrition labels appeared to be associated
      with a lower prevalence of MetS in a nationally representative sample of Korean
      adults.

PMID- 23146360
TI  - Dietary patterns as compared with physical activity in relation to metabolic
      syndrome among Chinese adults.
AB  - AIMS: To examine the nationally-representative dietary patterns and their joint
      effects with physical activity on the likelihood of metabolic syndrome (MS) among
      20,827 Chinese adults. METHODS AND RESULTS: CNNHS was a nationally representative
      cross-sectional observational study. Metabolic syndrome was defined according to
      the Joint Interim Statement definition. The "Green Water" dietary pattern,
      characterized by high intakes of rice and vegetables and moderate intakes in
      animal foods was related to the lowest prevalence of MS (15.9%). Compared to the
      "Green Water" dietary pattern, the "Yellow Earth" dietary pattern, characterized
      by high intakes of refined cereal products, tubers, cooking salt and salted
      vegetable was associated with a significantly elevated odds of MS (odds ratio
      1.66, 95%CI: 1.40-1.96), after adjustment of age, sex, socioeconomic status and
      lifestyle factors. The "Western/new affluence" dietary pattern characterized by
      higher consumption of beef/lamb, fruit, eggs, poultry and seafood also
      significantly associated with MS (odds ratio: 1.37, 95%CI: 1.13-1.67). Physical
      activity showed significant interactions with the dietary patterns in relation to
      MS risk (P for interaction = 0.008). In the joint analysis, participants with the
      combination of sedentary activity with the "Yellow Earth" dietary pattern or the
      "Western/new affluence" dietary pattern both had more than three times (95%CI:
      2.8-6.1) higher odds of MS than those with active activity and the "Green Water"
      dietary pattern. CONCLUSIONS: Our findings from the large Chinese national
      representative data indicate that dietary patterns affect the likelihood of MS.
      Combining healthy dietary pattern with active lifestyle may benefit more in
      prevention of MS.

PMID- 23146361
TI  - Response to the letter to editor regarding high-sugar drinks and impaired fasting
      glucose among Cree.

PMID- 23146362
TI  - Analytical lessons learned from selected therapeutic protein drug comparability
      studies.
AB  - The successful implementation of process and product changes for a therapeutic
      protein drug, both during clinical development and after commercialization,
      requires a detailed evaluation of their impact on the protein's structure and
      biological functionality. This analysis is called a comparability exercise and
      includes a data driven assessment of biochemical equivalence and biological
      characterization using a cadre of analytical methodologies. This review focuses
      on describing analytical results and lessons learned from selected published
      therapeutic protein comparability case studies both for bulk drug substance and
      final drug product. An overview of the currently available analytical
      methodologies typically used is presented as well as a discussion of new emerging
      analytical techniques. The potential utility of several novel analytical
      approaches to comparability studies is discussed including distribution and
      stability of protein drugs in vivo, and enhanced evaluation of higher-order
      protein structure in actual formulations using hydrogen/deuterium exchange mass
      spectrometry, two-dimensional nuclear magnetic resonance fingerprinting or
      empirical phase diagrams. In addition, new methods for detecting and
      characterizing protein aggregates and particles are presented as these degradants
      are of current industry-wide concern. The critical role that analytical
      methodologies play in elucidating the structure-function relationships for
      therapeutic protein products during the overall assessment of comparability is
      discussed.

PMID- 23146363
TI  - Novel forms of forgetting in temporal lobe epilepsy.
AB  - Transient Epileptic Amnesia (TEA) is a recently defined subtype of temporal lobe
      epilepsy, principally affecting people in middle age with a male predominance.
      Its key manifestation is the occurrence of recurring episodes of transient
      amnesia, usually lasting less than an hour and often occurring on waking. One
      third of patients have exclusively amnestic attacks, while in two-thirds, at
      least some attacks are accompanied by other manifestations of epilepsy,
      especially olfactory hallucinations. Several lines of evidence point to a seizure
      focus in the medial temporal lobes. Transient Epileptic Amnesia is accompanied by
      a striking loss of autobiographical memories in two-thirds of sufferers,
      accelerated loss of memories which had been acquired successfully in around one
      half, and topographical amnesia in around one-third. This paper reviews the
      findings of the TIME project (The Impairment of Memory in Epilepsy -
      http://sites.pcmd.ac.uk/time/tea.php) in relation to TEA, accelerated long-term
      forgetting, and remote memory impairment.

PMID- 23146364
TI  - The epilepsies: complex challenges needing complex solutions.
AB  - It is widely accepted that epilepsies are complex syndromes due to their multi
      factorial origins and manifestations. Different mathematical and computational
      descriptions use appropriate methods to address nonlinear relationships, chaotic
      behaviors and emergent properties. These theoretical approaches can be divided
      into two major categories: descriptive, such as flowcharts, graphs and other
      statistical analyses, and explicative, which include both realistic and abstract
      models. Although these modeling tools have brought great advances, a common
      framework to guide their design, implementation and evaluation, with the goal of
      future integration, is still needed. In the current review, we discuss two
      examples of complexity analysis that can be performed with epilepsy data:
      behavioral sequences of temporal lobe seizures and alterations in an experimental
      cellular model. We also highlight the importance of the creation of model
      repositories for the epileptology field and encourage the development of
      mathematical descriptions of complex systems, together with more accurate
      simulation techniques.

PMID- 23146365
TI  - Prevalence of unrecognized lower extremity peripheral arterial disease and the
      associated factors in chinese hypertensive adults.
AB  - We aimed to examine the prevalence of lower-extremity peripheral artery disease
      (LE-PAD) and its associated factors in 3,128 Chinese hypertensive adults 45 to 75
      years old without known cardiovascular disease, PAD, chronic kidney disease,
      diabetes, and dyslipidemia. A cross-sectional investigation was carried out in a
      rural area of Lianyungang, China. An ankle-brachial index <=0.90 in either leg
      was used to define LE-PAD. Prevalence of LE-PAD was 9.0% (10.0% in women and 7.4%
      in men). In the multivariable logistic regression model, odds ratios (95%
      confidence interval) of having LE-PAD, were 1.82 (1.27 to 2.61) for participants
      65 to 75 versus 45 to 55 years old, 1.48 (1.00 to 1.20) for participants with a
      waist circumference >=90 versus <90 cm, 1.47 (1.05 to 2.04) and 1.62 (1.15 to
      2.27) for participants with grade 2 and 3 hypertension versus controlled blood
      pressure or grade 1 hypertension, 1.35 (1.00 to 1.83) and 1.61 (1.16 to 2.23) for
      participants with heart rate at rest 70 to 80 and >=80 versus <70 beats/min, and
      1.41 (1.00 to 1.97) for participants with poor versus good sleeping quality. For
      other risk factors, gender-related differences were observed. Adjusted odds
      ratios of having LE-PAD for men and women were 1.07 (0.66 to 1.74) and 0.65 (0.47
      to 0.90) for inland versus coastal residents and 1.03 (0.57 to 1.86) and 1.62
      (1.09 to 2.41) for participants with body mass index >=25 versus <25 kg/m(2). In
      conclusion, there was a high prevalence of LE-PAD in Chinese hypertensive adults
      without known cardiovascular disease, PAD, chronic kidney disease, diabetes, and
      dyslipidemia, particularly in women in coastal areas and in participants with
      higher heart rate and poor sleeping quality. Therefore, ankle-brachial index
      determinations should be encouraged in clinical practice in Chinese hypertensive
      adults.

PMID- 23146366
TI  - Use of knotless suture for closure of total hip and knee arthroplasties: a
      prospective, randomized clinical trial.
AB  - We performed a prospective, randomized clinical trial to evaluate the efficacy of
      using a bidirectional barbed suture compared with traditional sutures in the deep
      closure of primary total hip (25) and knee (35) arthroplasties. Complications,
      time to closure, and length of surgery were evaluated. Closure was noted to be
      significantly faster (9.3 vs 13.6 minutes, P < .005) in the barbed suture group.
      Wound-related complications were similar (3 cases) in both groups at 3-month
      follow-up. Although this study supports the use of barbed technology as a
      functionally comparable and more efficient modality of wound closure with the
      potential for costs savings based on reduced operative time, the cost
      effectiveness of its adoption is institution dependent and will rely on the
      optimization of all other perioperative factors.

PMID- 23146367
TI  - Removed antibiotic-impregnated cement spacers in two-stage revision joint
      arthroplasty do not show biofilm formation in vivo.
AB  - Use of antibiotic-impregnated spacers is common in the two-stage approach to
      treatment of periprosthetic joint infection despite the lack of information
      regarding in vivo performance of these implants. Antibiotic elution levels likely
      often fall below the minimal inhibitory concentration need to inhibit bacterial
      growth, raising concern that the spacers themselves may provide a potential
      attachment site for biofilm formation. Advanced microscopy was used in this study
      to evaluate the surface characteristics of antibiotic-eluting spacers collected
      at the time of prosthesis reimplantation from 6 patients undergoing two-stage
      treatment for an infected total joint arthroplasty. Scanning electron microscopy
      and confocal scanning microscopy of the removed spacers revealed modest fibrous
      matrix formation and inflammatory cells with no biofilm or bacteria detected.
      This study supports the continued use of antibiotic spacers in the treatment of
      periprosthetic joint infection.

PMID- 23146368
TI  - Ten- to 15-year clinical and radiographic results for a compression molded
      monoblock elliptical acetabular component.
AB  - The aim of this study was to report the long-term results from a previously
      published midterm follow-up of a titanium monoblock, elliptical acetabular
      component. A total of 258 primary total hip arthroplasties (212 patients) with a
      monoblock, acetabular component were followed up for a mean period of 11.1 years
      (10-15). Average yearly wear rate was 0.08 mm/y (0.0009-0.32). Acetabular
      radiolucencies were present in 6 hips (2.4%); all were nonprogressive and present
      in acetabular zone I. Acetabular osteolysis was present in 5 patients (5 hips,
      1.9%); all cups were stable. Four acetabular components were revised, 3 because
      of recurrent instability. No acetabular components were revised for polyethylene
      wear or dissociation, acetabular osteolysis, loosening, or deep infection. This
      monoblock design demonstrates excellent long-term survival and low rate of
      osteolysis.

PMID- 23146369
TI  - Characteristics of women using organized or opportunistic breast cancer screening
      in France. Analysis of the 2006 French Health, Health Care and Insurance Survey.
AB  - BACKGROUND: This study aimed at (i) estimating the 2-year self-reported breast
      cancer screening coverage rate; and (ii) analyzing the relationships between
      sociodemographic characteristics and healthcare access of women and breast cancer
      screening (opportunistic or organized) practices. METHODS: From a 2006 French
      health survey, 2056 women aged 50 to 74 years were selected and divided into
      three groups according to their breast cancer screening practices during the
      previous 2 years: organized screening, opportunistic screening, or no screening.
      The three groups were compared according to self-reported sociodemographic
      status, healthcare access, screening behaviors, and perceived health, using
      polytomic regression. RESULTS: The 2-year self-reported coverage rate was 75.8%.
      It was high among women aged 50 to 69 years and lower among older women.
      Questions relating to medical access (i.e. having consulted a GP in the last 12
      months, having consulted a gynecologist in the last 12 months, and having had a
      Pap smear in the last 3 years) were the variables most commonly associated with a
      recent mammogram. Women having a regular follow-up by a gynecologist or having
      had cervical cancer screening within the last three years used organized breast
      cancer screening more often and used opportunistic breast cancer screening even
      more often than other women. CONCLUSION: The study confirmed the key role of
      gynecologists and general practitioners in encouraging women to have a mammogram.
      Awareness among healthcare professionals and women of the benefits of organized
      breast cancer screening compared to opportunistic screening should be sustained
      and strengthened.

PMID- 23146370
TI  - High levels of very long-chain saturated fatty acid in erythrocytes correlates
      with atherogenic lipoprotein profiles in subjects with metabolic syndrome.
AB  - AIM: Very long chain saturated fatty acid (VLCFA) levels in erythrocytes are
      associated with metabolic syndrome (MS). However, the relationship between levels
      of the VLCFA ligonoceric acid (C24:0) in erythrocytes and the atherogenic
      lipoprotein profiles and inflammatory state in MS remain unclear. METHODS: Based
      on the International Diabetes Federation (IDF) definition of MS, 195 apparently
      healthy males were assigned to either an MS group (n=38) or a non-MS group
      (n=157). Fatty acid composition of erythrocytes was determined by gas liquid
      chromatography. RESULTS: Erythrocytes from the MS group had a significantly
      higher level of C24:0 than cells from the non-MS group (4.06+/-0.48% versus
      3.88+/-0.34%; p=0.03). C24:0 levels were significantly correlated with several
      components of MS. The C24:0 levels showed a significant negative correlation with
      LDL and HDL particle size. Multivariate linear regression analysis showed that
      C24:0 levels were independently correlated with LDL particle size after adjusting
      for age and each MS criterion. C24:0 levels were also positively correlated with
      log-transformed high-sensitivity CRP levels (p=0.04). CONCLUSION: C24:0 levels in
      erythrocytes are associated with specific atherogenic lipoprotein profiles and
      inflammation status in subjects with MS.

PMID- 23146371
TI  - Carbohydrate counting accuracy and blood glucose variability in adults with type
      1 diabetes.
AB  - AIMS: Carbohydrate counting is an established approach used by patients with type
      1 diabetes to improve their glycemic control. The aims of this study were to
      evaluate, in real life conditions, the accuracy of meal carbohydrate estimate and
      its impact on glycemic variability. METHODS: In this cross-sectional study, we
      observed the ability of 50 adults (48% women) with type 1 diabetes (age: 42.7+/
      11.1 years); diabetes duration: 21.4+/-12.7 years; HbA1c: 7.2+/-1.2% (60+/-10
      mmol/mol) to accurately estimate carbohydrates by analyzing 72-h food records and
      their corresponding 72-h blood glucose excursions using a continuous glucose
      monitor. RESULTS: The mean meal carbohydrate difference, between the patients'
      estimates and those assessed by a dietitian using a computerized analysis
      program, was 15.4+/-7.8 g or 20.9+/-9.7% of the total CHO content per meal
      (72.4+/-34.7 g per meal). Sixty-three percent of the 448 meals analyzed were
      underestimated. Greater differences in CHO's estimates predicted higher glycemic
      variability, as measured by the MAGE index and glucose standard deviation, and
      decreased time with glucose values between 4 and 10 mmol/L (R2=0.110, 0.114 and
      0.110, respectively; P<0.05). CONCLUSION: Inaccurate carbohydrate counting is
      frequent and associated with higher daily blood glucose variability in adults
      with type 1 diabetes.

PMID- 23146372
TI  - Seven-day subcutaneous continuous glucose monitoring demonstrates that treatment
      with acarbose attenuates late dumping syndrome in a woman with gastrectomy for
      gastric cancer.

PMID- 23146373
TI  - Lanthanide mesoporous SBA-15 hybrids through functionalized 6
      hydroxybenz[de]anthracen-7-one linkage: UV-visible light sensitisation and
      visible-NIR luminescence.
AB  - A series of new visible and near-infrared (NIR) luminescent lanthanide
      hydroxybenz[de]anthracen derivatives (Ln(HBAN)(3)(H(2)O)(2)(NO(3))(3),
      Ln(HBAN)(3)phen(NO(3))(3)) were synthesized (HBAN-6-hydroxybenz[de]anthracen-7
      one, Ln=Eu, Yb, Nd). Further, chemically bonded lanthanide hybrids of
      functionalized mesoporous silica (SBA-15) are prepared using HBAN-functionalized
      alkoxysilane (HBAN-Si) as linker, which is named as Ln(HBAN-SBA-15)(3)(NO(3))(3),
      Ln(HBAN-SBA-15)(3)phen(NO(3))(3) (Ln=Eu, Yb, Nd), respectively. The physical
      characterization and especially the photoluminescence properties for these
      hybrids are performed. SAXRD and BET of them revealed that all of these hybrid
      materials have uniformity in the mesostructure. Worth noting here is that the
      excitation spectra of these hybrid materials are extended to visible light region
      (439-535 nm). Upon ligand-mediated excitation with the ultraviolet and visible
      light, the visible luminescence for europium hybrids and NIR luminescence for
      Yb(3+) and Nd(3+) hybrids are obtained.

PMID- 23146374
TI  - Parent cough-specific quality of life: development and validation of a short
      form.
AB  - BACKGROUND: Cough is a distressing symptom and has a significant effect on many
      children and their families. Quality-of-life (QOL) measures provide important
      outcome indicators for clinicians and aid in evaluating the efficacy of
      interventions. OBJECTIVE: The aim of this study was to develop and validate a
      short cough-specific QOL questionnaire for pediatric use. METHOD: Two sources
      provided data to establish a shortened version of the Parent Cough-specific
      Quality of Life (PC-QOL) questionnaire. The first (n=240, 137 boys; median age,
      29 months [interquartile range, 14-64 months]) was used for development and cross
      validation. Stepwise regression was used to select the reduced set of items, and
      analyses of reliability, validity, and minimally important differences determined
      psychometric strength and sensitivity to change. The second independent dataset
      (n=320, 190 boys; median age, 39.5 months [interquartile range, 16-77 months])
      was used as a confirmatory sample. RESULTS: Forward-step regression identified 8
      items that accounted for 95% of the variance in the full-scale PC-QOL
      questionnaire. This shortened version (PC-QOL-8) was internally consistent
      (Cronbach alpha=0.84), had good test-retest reliability (intraclass correlation
      coefficient=0.66), and demonstrated strong validity (significant correlations
      with a cough verbal category descriptor score, cough visual analog scale, and
      subscales of the Short Form-12 General Health scale, the Pediatric Quality of
      Life Inventory, and the Depression, Anxiety, and Stress Scale). The reduced scale
      was responsive to change, and a minimally important difference of 0.9 was
      suggested. These findings were confirmed with the second dataset. CONCLUSION: The
      PC-QOL-8 questionnaire is a short, reliable, and valid instrument for assessing
      the effect of a child's chronic cough. It demonstrated sensitivity to change, and
      its length and psychometric properties should enhance its potential uptake and
      routine use in clinical practice and research.

PMID- 23146375
TI  - Induced bronchospasm after handling of orange flavedo (zest).

PMID- 23146376
TI  - Peripheral airway impairment measured by oscillometry predicts loss of asthma
      control in children.
AB  - BACKGROUND: We previously showed that impulse oscillometry (IOS) indices of
      peripheral airway function are associated with asthma control in children.
      However, little data exist on whether dysfunction in the peripheral airways can
      predict loss of asthma control. OBJECTIVE: We sought to determine the utility of
      peripheral airway impairment, as measured by IOS, in predicting loss of asthma
      control in children. METHODS: Fifty-four children (age, 7-17 years) with
      controlled asthma were enrolled in the study. Spirometric and IOS indices of
      airway function were obtained at baseline and at a follow-up visit 8 to 12 weeks
      later. Physicians who were blinded to the IOS measurements assessed asthma
      control (National Asthma Education and Prevention Program guidelines) on both
      visits and prescribed no medication change between visits. RESULTS: Thirty-eight
      (70%) patients maintained asthma control between 2 visits (group C-C), and 16
      patients had asthma that became uncontrolled on the follow-up visit (group C-UC).
      There was no difference in baseline spirometric results between the C-C and C-UC
      groups, except for FEV1/forced vital capacity ratio (86% vs 82%, respectively; P
      < .01). Baseline IOS results, including resistance of the respiratory system at 5
      Hz (R5; 6.4 vs 4.3 cm H2O . L(-1) . s), frequency dependence of resistance
      (difference of R5 and resistance of the respiratory system at 20 Hz [R5-20]; 2.0
      vs 0.7 cm H2O . L(-1) . s), and reactance area (13.1 vs 4.1 cm H2O . L(-1)), of
      group C-UC were significantly higher than those of group C-C (P < .01). Receiver
      operating characteristic analysis showed baseline R5-20 and reactance area
      effectively predicted asthma control status at the follow-up visit (area under
      the curve, 0.91 and 0.90). CONCLUSION: Children with controlled asthma who have
      increased peripheral airway IOS indices are at risk of losing asthma control.

PMID- 23146377
TI  - Pancreatitis as a complication of aspirin desensitization for aspirin-exacerbated
      respiratory disease.

PMID- 23146378
TI  - Reply: To PMID 22236727.

PMID- 23146379
TI  - Gender differences in the bronchoalveolar lavage cell proteome of patients with
      chronic obstructive pulmonary disease.
AB  - BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a leading cause of
      morbidity and mortality worldwide and is increasing, primarily among women.
      Underdiagnosis is common, and because of the heterogeneous disease
      characteristics, molecular markers of specific disease phenotypes and more
      efficacious treatment regimens are urgently needed. OBJECTIVE: In this study the
      soluble proteome of bronchoalveolar lavage cells, primarily consisting of
      macrophages, was investigated with the aim of identifying phenotypic differences
      in early disease development. METHODS: Two-dimensional difference gel
      electrophoresis was used for relative quantification of protein levels, and
      multivariate modeling was applied to identify proteins of interest that were
      subsequently identified by means of liquid chromatography-mass spectrometry.
      RESULTS: Significant gender differences were unveiled, with numerous alterations
      in the bronchoalveolar lavage cell proteome occurring in female but not male
      patients with COPD. Specifically, a subset of 19 proteins provided classification
      of female healthy smokers from female patients with COPD with 78% predictive
      power. Subsequent pathway analyses linked the observed alterations to
      downregulation of the lysosomal pathway and upregulation of the oxidative
      phosphorylation pathway, possibly linking dysregulation of macroautophagy to a
      female-dominated COPD disease phenotype. CONCLUSION: This investigation makes an
      important contribution to the elucidation of putative molecular mechanisms
      underlying gender-based differences in the pathophysiology of COPD, linking
      alterations of specific molecular pathways to previously observed gender
      differences in clinical COPD phenotypes. Furthermore, these results stress the
      importance of the gender-specific search for biomarkers, diagnosis, and treatment
      in COPD.

PMID- 23146380
TI  - Sputum hydrogen sulfide as a novel biomarker of obstructive neutrophilic asthma.

PMID- 23146383
TI  - Genotypic and phenotypic analysis of familial male breast cancer shows under
      representation of the HER2 and basal subtypes in BRCA-associated carcinomas.
AB  - BACKGROUND: Male breast cancer (MBC) is an uncommon and relatively
      uncharacterised disease accounting for <1% of all breast cancers. A significant
      proportion occurs in families with a history of breast cancer and in particular
      those carrying BRCA2 mutations. Here we describe clinicopathological features and
      genomic BRCA1 and BRCA2 mutation status in a large cohort of familial MBCs.
      METHODS: Cases (n=60) included 3 BRCA1 and 25 BRCA2 mutation carries, and 32 non
      BRCA1/2 (BRCAX) carriers with strong family histories of breast cancer. The
      cohort was examined with respect to mutation status, clinicopathological
      parameters including TNM staging, grade, histological subtype and intrinsic
      phenotype. RESULTS: Compared to the general population, MBC incidence was higher
      in all subgroups. In contrast to female breast cancer (FBC) there was greater
      representation of BRCA2 tumours (41.7% vs 8.3%, p=0.0008) and underrepresentation
      of BRCA1 tumours (5.0% vs 14.4%, p=0.0001). There was no correlation between
      mutation status and age of onset, disease specific survival (DSS) or other
      clincopathological factors. Comparison with sporadic MBC studies showed similar
      clinicopathological features. Prognostic variables affecting DSS included primary
      tumour size (p=0.003, HR:4.26 95%CI 1.63-11.11), age (p=0.002, HR:4.09 95%CI 1.65
      10.12), lymphovascular (p=0.019, HR:3.25 95%CI 1.21-8.74) and perineural invasion
      (p=0.027, HR:2.82 95%CI 1.13-7.06). Unlike familial FBC, the histological
      subtypes seen in familial MBC were more similar to those seen in sporadic MBC
      with 46 (76.7%) pure invasive ductal carcinoma of no special type (IDC-NST), 2
      (3.3%) invasive lobular carcinomas and 4 (6.7%) invasive papillary carcinoma. A
      further 8 (13.3%) IDC-NST had foci of micropapillary differentiation, with a
      strong trend for co-occurrence in BRCA2 carriers (p=0.058). Most tumours were of
      the luminal phenotype (89.7%), with infrequent HER2 (8.6%) and basal (1.7%)
      phenotype tumours seen. CONCLUSION: MBC in BRCA1/2 carriers and BRCAX families is
      different to females. Unlike FBC, a clear BRCA1 phenotype is not seen but a
      possible BRCA2 phenotype of micropapillary histological subtype is suggested.
      Comparison with sporadic MBCs shows this to be a high-risk population making
      further recruitment and investigation of this cohort of value in further
      understanding these uncommon tumours.

PMID- 23146382
TI  - Human rhinovirus C: Age, season, and lower respiratory illness over the past 3
      decades.
AB  - BACKGROUND: Human rhinoviruses (HRVs) cause common colds, and the recently
      discovered HRV-C is increasingly associated with lower respiratory illness among
      populations such as children and asthmatic patients. OBJECTIVE: To determine how
      HRV-C is associated with respiratory illness and to evaluate changes in
      prevalence and species over 2 decades. METHODS: A prospective study of children
      younger than 5 years was performed at the Vanderbilt Vaccine Clinic over a 21
      year period. Nasal-wash specimens from children presenting with upper or lower
      respiratory illness at acute care visits were tested for HRV and HRV-positives
      genotyped. Demographic and clinical features were compared between children with
      or without HRV, and with different HRV species. RESULTS: HRV was detected in 190
      of 527 (36%) specimens from a population of 2009 children from 1982 through 2003.
      Of these, 36% were HRV-C. Age (P = .039) and month of illness (P < .001) were
      associated with HRV infection and HRV species. HRV-C was significantly associated
      with lower respiratory illness, compared with HRV-A (P = .014). HRV-A and HRV-C
      prevalence fluctuated throughout the 21-year period; HRV-C was more prevalent
      during winter (P = .058). CONCLUSIONS: HRV-C is not a new virus but has been
      significantly associated with childhood lower respiratory illness in this
      population for several decades. Temporal changes in virus prevalence occur, and
      season may predict virus species. Our findings have implications for diagnostic,
      preventive, and treatment strategies due to the variation in disease season and
      severity based on species of HRV infection.

PMID- 23146385
TI  - Is alcohol intake associated with low back pain? A systematic review of
      observational studies.
AB  - BACKGROUND: Alcohol intake has been widely reported as a risk factor for low back
      pain (LBP), however, the literature is inconclusive about this association.
      OBJECTIVES: To determine, in a systematic review, the relationship between
      alcohol intake and LBP. METHODS: A search was conducted in CINAHL, LILACS,
      Medline, National Research Register and Web of Science to identify studies that
      investigated the association between alcohol intake and LBP. Quantitative results
      and its estimators were extracted. When possible, meta-analyses were performed
      using a random effects model. RESULTS: Twenty-six studies were included in this
      review. Twenty-three studies were retrospective cohorts, two were case-controls,
      and one employed a longitudinal design. Pooled results from nine studies (two
      case-controls and seven retrospective cohorts) showed that alcohol consumption is
      slightly associated with LBP (OR: 1.3; 95% CI: 1.1-1.5). This association appears
      to be present in studies investigating alcohol as an abuse dependence substance
      in chronic LBP. Remaining individual studies tended to report no statistical
      significant association. No dose-response relationship was identified. Only one
      longitudinal study was identified and even though alcohol consumption was found
      to be negatively associated with a future episode of LBP (OR: 0.7; 95% CI: 0.5
      0.9) this association lost significance for future incidence of LBP in people
      with no LBP at baseline. CONCLUSIONS: Alcohol consumption appears to be
      associated with complex and chronic LBP only and in people with alcohol
      consumption dependence. Clinicians in the musculoskeletal field could use this
      information to design educational strategies for this population.

PMID- 23146381
TI  - A meta-analysis of genome-wide association studies for serum total IgE in diverse
      study populations.
AB  - BACKGROUND: IgE is both a marker and mediator of allergic inflammation. Despite
      reported differences in serum total IgE levels by race-ethnicity, African
      American and Latino subjects have not been well represented in genetic studies of
      total IgE. OBJECTIVE: We sought to identify the genetic predictors of serum total
      IgE levels. METHODS: We used genome-wide association data from 4292 subjects
      (2469 African Americans, 1564 European Americans, and 259 Latinos) in the EVE
      Asthma Genetics Consortium. Tests for association were performed within each
      cohort by race-ethnic group (ie, African American, Latino, and European American)
      and asthma status. The resulting P values were meta-analyzed, accounting for
      sample size and direction of effect. Top single nucleotide polymorphism
      associations from the meta-analysis were reassessed in 6 additional cohorts
      comprising 5767 subjects. RESULTS: We identified 10 unique regions in which the
      combined association statistic was associated with total serum IgE levels
      (P<5.0*10(-6)) and the minor allele frequency was 5% or greater in 2 or more
      population groups. Variant rs9469220, corresponding to HLA-DQB1, was the single
      nucleotide polymorphism most significantly associated with serum total IgE levels
      when assessed in both the replication cohorts and the discovery and replication
      sets combined (P=.007 and 2.45*10(-7), respectively). In addition, findings from
      earlier genome-wide association studies were also validated in the current meta
      analysis. CONCLUSION: This meta-analysis independently identified a variant near
      HLA-DQB1 as a predictor of total serum IgE levels in multiple race-ethnic groups.
      This study also extends and confirms the findings of earlier genome-wide
      association analyses in African American and Latino subjects.

PMID- 23146384
TI  - A risk-adapted protocol for delayed administration of filgrastim after high-dose
      chemotherapy and autologous stem cell transplantation.
AB  - INTRODUCTION: The routine use of recombinant human granulocyte-colony stimulating
      factor (rhG-CSF) after high-dose chemotherapy and autologous stem cell
      transplantation (auto-SCT) is associated with increased costs. We prospectively
      explored a strategy that used prophylactic delayed filgrastim only in patients
      with risk factors. PATIENTS AND METHODS: This sequential cohort analysis compared
      the outcomes of consecutive patients, treated on the risk-adapted protocol (RAP)
      (risk factors: prior febrile neutropenia; age >60 years; and CD34+ cell infused
      dose of <2 * 10(6/)/kg), who received filgrastim from day +6 after auto-SCT with
      a historical cohort (historical day-1 cohort [HD1]), who received filgrastim from
      day +1. RESULTS: Eighty-two patients were treated in the RAP cohort and compared
      with 115 patients in the HD1 cohort. There were no differences in median age (55
      years) or median CD34+ cell dose (5.21 * 10(6)/kg [range, 2-62.2 * 10(6)/kg] vs.
      5.24 * 10(6)/kg [range, 2.4-29.8 * 10(6)/kg]). Filgrastim was used for 6 fewer
      days in the RAP cohort (median 5 days [range, 0-11 days] vs. 11 days [range, 9-47
      days]). There was a small absolute but significant difference in median time to
      neutrophil recovery in the HD1 cohort for the whole group, 10 days (range, 8-46
      days) vs. 11 days (range, 9-22 days) (P = .03) and in patients with myeloma; 10
      days (range, 9-14 days) vs. 11 days (range, 9-18 days) (P < .0001) as compared to
      the RAP cohort. There was no difference in median inpatient duration, 13 days
      (range, 10-26 days) vs. 12 days (range, 1-38 days) (P = .22) and 3-year survival
      (79% vs. 83% [P = .43]) between HD1 and RAP cohorts respectively. CONCLUSIONS:
      The use of a RAP to identify patients likely to benefit from prophylactic
      filgrastim is safe and results in cost savings. Patients with myeloma benefit
      from earlier introduction of filgrastim in terms of neutrophil recovery; this
      disease-specific observation is an important consideration for future studies.

PMID- 23146388
TI  - Introduction.

PMID- 23146386
TI  - A critical role for the TLR4/TRIF pathway in allogeneic hematopoietic cell
      rejection by innate immune cells.
AB  - We show for the first time that signaling through the TLR4/TRIF pathway plays a
      critical role in allogeneic bone marrow cell (BMC) rejection. This appears to be
      unique to BMCs as organ allografts are rejected mainly via MyD88 signaling. Using
      T- or T-/B-cell-deficient mice, we found that BMC allorejection occurred early
      before T-cell activation and was T- and B-cell independent, suggesting an
      effector role for innate immune cells in BMC rejection. We further demonstrated
      the innate immune signaling in BMC allorejection by showing superior engraftment
      in mice deficient in TRIF or TLR4 but not in MyD88 or TLR3. The restored
      cytotoxicity in TRIF-deficient recipients transferred with wild-type F4/80(+) or
      NK1.1(+) cells suggests TRIF signaling dependence on macrophages or NK cells in
      early BMC rejection. Production of the proinflammatory cytokine IL-6 and TRIF
      relevant chemokine MCP-1 was significantly increased early after bone marrow
      transplantation. In vivo specific depletion of macrophages or NK innate immune
      cells in combination with anti-CD154/rapamycin resulted in additive-enhanced
      allogeneic engraftment. The requirement for irradiation was completely eliminated
      when both macrophages and NK cells were depleted in combination with anti
      CD154/rapamycin to target T- and B-cells, supporting the hypothesis that two
      barriers involving innate and adaptive immunity exist in mediating the rejection
      of allogeneic BMCs. In summary, our results clearly demonstrate a previously
      unappreciated role for innate immunity in BMC allorejection via signaling through
      a unique MyD88-independent TLR4/TRIF mechanism. These findings may have direct
      clinical impact on strategies for conditioning recipients for stem cell
      transplantation. 

PMID- 23146389
TI  - Applications of synchrotron MU-XRF to study the distribution of biologically
      important elements in different environmental matrices: a review.
AB  - Environmental matrices including soils, sediments, and living organisms are
      reservoirs of several essential as well as non-essential elements. Accurate
      qualitative and quantitative information on the distribution and interaction of
      biologically significant elements is vital to understand the role of these
      elements in environmental and biological samples. Synchrotron micro-X-ray
      fluorescence (MU-SXRF) allows in situ mapping of biologically important elements
      at nanometer to sub-micrometer scale with high sensitivity, negligible sample
      damage and enable tuning of the incident energy as desired. Beamlines in the
      synchrotron facilities are rapidly increasing their analytical versatility in
      terms of focusing optics, detector technologies, incident energy, and sample
      environment. Although extremely competitive, it is now feasible to find stations
      offering complimentary techniques like micro-X-ray diffraction (MU-XRD) and micro
      X-ray absorption spectroscopy (MU-XAS) that will allow a more complete
      characterization of complex matrices. This review includes the most recent
      literature on the emerging applications and challenges of MU-SXRF in studying the
      distribution of biologically important elements and manufactured nanoparticles in
      soils, sediments, plants, and microbes. The advantages of using MU-SXRF and
      complimentary techniques in contrast to conventional techniques used for the
      respective studies are discussed.

PMID- 23146387
TI  - Factors affecting deer ked (Lipoptena cervi) prevalence and infestation intensity
      in moose (Alces alces) in Norway.
AB  - BACKGROUND: The deer ked (Lipoptena cervi), a hematophagous ectoparasite of
      Cervids, is currently spreading in Scandinavia. In Norway, keds are now invading
      the south-eastern part of the country and the abundant and widely distributed
      moose (Alces alces) is the definitive host. However, key factors for ked
      abundance are poorly elucidated. The objectives of our study were to (i)
      determine deer ked infestation prevalence and intensity on moose and (ii)
      evaluate if habitat characteristics and moose population density are determinants
      of deer ked abundance on moose. METHODS: In order to identify key factors for
      deer ked abundance, a total of 350 skin samples from the neck of hunted moose
      were examined and deer keds counted. Infestation intensity was analyzed in
      relation to moose age and sex, moose population density and landscape
      characteristics surrounding the killing site. RESULTS: Deer ked infestation
      prevalence was 100%, but infestation intensity varied from 0.001 to 1.405
      keds/cm2. Ked intensity was highest in male yearlings (~1.5 years) and positively
      associated with longitude and Scots pine (Pinus sylvestris) dominated habitat and
      negatively associated with bogs and latitude. Moose population density during
      autumn showed a tendency to be positively associated, while altitude tended to be
      negatively associated with ked intensity. CONCLUSIONS: Deer keds exploit the
      whole moose population within our study area, but are most prevalent in areas
      dominated by Scots pine. This is probably a reflection of Scots pine being the
      preferred winter browse for moose in areas with highest moose densities in
      winter. Ked intensity decreases towards the northwest and partly with increasing
      altitude, probably explained by the direction of dispersal and reduced
      temperature, respectively. Abundant deer ked harm humans and domestic animals.
      Moose management authorities should therefore be aware of the close relationship
      between moose, deer ked and habitat, using the knowledge as a management tool for
      locally regulating the ked burden.

PMID- 23146390
TI  - Photon level chemical classification using digital compressive detection.
AB  - A key bottleneck to high-speed chemical analysis, including hyperspectral imaging
      and monitoring of dynamic chemical processes, is the time required to collect and
      analyze hyperspectral data. Here we describe, both theoretically and
      experimentally, a means of greatly speeding up the collection of such data using
      a new digital compressive detection strategy. Our results demonstrate that
      detecting as few as ~10 Raman scattered photons (in as little time as ~30 MUs)
      can be sufficient to positively distinguish chemical species. This is achieved by
      measuring the Raman scattered light intensity transmitted through programmable
      binary optical filters designed to minimize the error in the chemical
      classification (or concentration) variables of interest. The theoretical results
      are implemented and validated using a digital compressive detection instrument
      that incorporates a 785 nm diode excitation laser, digital micromirror spatial
      light modulator, and photon counting photodiode detector. Samples consisting of
      pairs of liquids with different degrees of spectral overlap (including
      benzene/acetone and n-heptane/n-octane) are used to illustrate how the accuracy
      of the present digital compressive detection method depends on the correlation
      coefficients of the corresponding spectra. Comparisons of measured and predicted
      chemical classification score plots, as well as linear and non-linear
      discriminant analyses, demonstrate that this digital compressive detection
      strategy is Poisson photon noise limited and outperforms total least squares
      based compressive detection with analog filters.

PMID- 23146391
TI  - Mass spectrometry fingerprinting coupled to National Institute of Standards and
      Technology Mass Spectral search algorithm for pattern recognition.
AB  - A new analytical strategy based on mass spectrometry fingerprinting combined with
      the NIST-MS search program for pattern recognition is evaluated and validated. A
      case study dealing with the tracing of the geographical origin of virgin olive
      oils (VOOs) proves the capabilities of mass spectrometry fingerprinting coupled
      with NIST-MS search program for classification. The volatile profiles of 220 VOOs
      from Liguria and other Mediterranean regions were analysed by secondary
      electrospray ionization-mass spectrometry (SESI-MS). MS spectra of VOOs were
      classified according to their origin by the freeware NIST-MS search v 2.0. The
      NIST classification results were compared to well-known pattern recognition
      techniques, such as linear discriminant analysis (LDA), partial least-squares
      discriminant analysis (PLS-DA), k-nearest neighbours (kNN), and counter
      propagation artificial neural networks (CP-ANN). The NIST-MS search program
      predicted correctly 96% of the Ligurian VOOs and 92% of the non-Ligurian ones of
      an external independent data set; outperforming the traditional chemometric
      techniques (prediction abilities in the external validation achieved by kNN were
      88% and 84% for the Ligurian and non-Ligurian categories respectively). This
      proves that the NIST-MS search software is a useful classification tool.

PMID- 23146392
TI  - Application of parallel factor analysis to total synchronous fluorescence
      spectrum of dilute multifluorophoric solutions: addressing the issue of lack of
      trilinearity in total synchronous fluorescence data set.
AB  - In recent years, total synchronous fluorescence (TSF) spectroscopy has become
      popular for the analysis of multifluorophoric systems. Application of PARAFAC, a
      popular deconvolution tool, requires trilinear structure in the three-way data
      array. The present work shows that TSF based three-way array data set of
      dimension sample * wavelength * Deltalambda does not have trilinear structure and
      hence it should not be subjected to PARAFAC analysis. This work also proposes
      that a TSF data set can be converted to an excitation-emission matrix
      fluorescence (EEMF) like data set which has trilinear structure, so that PARAFAC
      analysis can be performed on it. This also enables the retrieval of PARAFAC
      separated component TSF spectra.

PMID- 23146393
TI  - A dual-amplification aptasensor for highly sensitive detection of thrombin based
      on the functionalized graphene-Pd nanoparticles composites and the hemin/G
      quadruplex.
AB  - In this work, an advanced sandwich-type electrochemical aptasensor for thrombin
      was proposed by integrating hemin/G-quadruplex with functionalized graphene-Pd
      nanoparticles composites (PdNPs-RGs). The hemin/G-quadruplex formed by
      intercalating hemin into thrombin binding aptamer (TBA), firstly acted as a NADH
      oxidase, assisting the oxidation of NADH to NAD(+) accompanying with the
      generation of H(2)O(2) in the presence of dissolved O(2). Subsequently, the
      hemin/G-quadruplex acted as HRP-mimicking DNAzyme that rapidly bioelectrocatalyze
      the reduction of the produced H(2)O(2). At the same time, the Pd nanoparticles
      supported on p-iodoaniline functionalized graphene were also adopted to catalyze
      the reduction of H(2)O(2). Thus, with the dual catalysis, a dramatically
      amplified electrochemical signal could be obtained. Besides, the avidin-biotin
      system for binding aptamer sequences on electrodes not only improved the
      sensitivity of thrombin analysis but also obtained an acceptable repeatability of
      the aptasensor. With several factors mentioned above, a wide linear ranged from
      0.1 pM to 50 nM was acquired with a relatively low detection limit of 0.03 pM
      (defined as S/N=3). These excellent performances provided our approach a
      promising way for ultrasensitive assay in electrochemical aptasensors.

PMID- 23146394
TI  - A cation trap for anodic stripping voltammetry: NH3-plasma treated carbon
      nanotubes for adsorption and detection of metal ions.
AB  - NH(3)-plasma treated multi-walled carbon nanotubes (pn-MWCNTs) with cation traps
      for the detection of ultratrace quantities of Zn(II), Cd(II), Cu(II), and Hg(II)
      using square wave anodic stripping voltammetry (SWASV) is described. The pn
      MWCNTs use their adsorption performance to enhance the sensitivity. It is found
      that under optimized conditions Zn(II), Cd(II), Cu(II) and Hg(II) were
      individually detected at potentials of -1.16, -0.78, -0.268 and 0.108 V,
      respectively. The detection limit (3sigma method) of 0.314, 0.0272, 0.2263, and
      0.1439 nM toward Zn(II), Cd(II), Cu(II), and Hg(II) is achievable, respectively.
      No interference could be seen during the simultaneous detection of Zn(II),
      Cd(II), Cu(II), and Hg(II). The pn-MWCNTs exhibit excellent selectivity owing to
      the different ability of adsorption. A study of the ability of pn-MWCNTs in
      practical application is carried out using a sample of water collected from
      Dongpu Reservoir in Hefei City, Anhui, China. It is found that the results were
      favorable when compared against inductively coupled plasma atomic emission
      spectrometry (ICP-AES) analysis.

PMID- 23146395
TI  - Enzyme-catalyzed silver deposition on irregular-shaped gold nanoparticles for
      electrochemical immunoassay of alpha-fetoprotein.
AB  - A new and disposable electrochemical immunosensor was designed for detection of
      alpha-fetoprotein (AFP), as a model analyte, with sensitivity enhancement based
      on enzyme-catalyzed silver deposition onto irregular-shaped gold nanoparticles
      (ISGNPs). The assay was carried out with a sandwich-type immunoassay protocol by
      using ISGNP-labeled anti-AFP antibodies conjugated with alkaline phosphatase (ALP
      Ab(2)) as detection antibodies. The enzymatically catalytic deposition of silver
      on the electrode could be measured by stripping analysis in KCl solution due to
      the Ag/AgCl solid-state voltammetric process. Several labeling protocols
      including spherical gold nanoparticle-labeled ALP-Ab(2) and ISGNP-labeled ALP
      Ab(2) were investigated for determination of AFP, and improved analytical
      properties were achieved with the ISGNP labeling. With the ISGNP labeling method,
      the effects of incubation time and incubation temperature for antigen-antibody
      reaction, and deposition time of silver on the current responses of the
      electrochemical immunosensors were also monitored. Under optimal conditions, the
      electrochemical immunosensor exhibited a wide dynamic range from 0.01 ng mL(-1)
      to 200 ng mL(-1) with a detection limit of 5.0 pg mL(-1) AFP. The immunosensor
      displayed a good stability and acceptable reproducibility and accuracy. No
      significant differences at the 95% confidence level were encountered in the
      analysis of 10 clinical serum samples between the developed immunoassay and the
      commercially available electrochemiluminescent method for determination of AFP.

PMID- 23146396
TI  - Development of an analytical methodology for the determination of the
      antiparasitic drug toltrazuril and its two metabolites in surface water, soil and
      animal manure.
AB  - This paper presents the development, optimization and validation of a LC-MS/MS
      methodology to determine the antiparasitic veterinary drug toltrazuril and its
      two main metabolites, toltrazuril sulfoxide and toltrazuril sulfone, in
      environmental surface water, soil and animal manure. Using solid phase extraction
      and selective pressurized liquid extraction with integrated clean-up, the
      analytical method allows for the determination of these compounds down to 0.06
      0.13 ng L(-1) in water, 0.01-0.03 ng g(-1)dw in soil and 0.22-0.51 ng g(-1) dw in
      manure. The deuterated analog of toltrazuril was used as internal standard, and
      ensured method accuracy in the range 96-123% for water and 77-110% for soil
      samples. The developed method can also be applied to simultaneously determine
      steroid hormones in the solid samples. The antiparasitic drug and its metabolites
      were found in manure and soil up to 114 and 335 pg g(-1) dw, respectively. Little
      is known regarding the environmental fate and effects of these compounds;
      consequently more research is urgently needed.

PMID- 23146397
TI  - Revisiting extraction of bioactive apocarotenoids from Crocus sativus L. dry
      stigmas (saffron).
AB  - An ultrasound assisted extraction method is proposed for the recovery of
      bioactive glycosides (i.e. crocins and picrocrocin) from Crocus sativus L. dry
      stigmas using aqueous methanol. Response surface methodology (RSM) was employed
      to optimize the extraction parameters, namely, the percentage of methanol (%),
      the duration (min) and the duty cycles (s) of sonication. Optical microscopy,
      spectrophotometry and RP-HPLC-DAD were employed to follow pros and cons of the
      process. Additional experiments were conducted to compare recoveries with those
      under other agitation conditions (e.g. magnetic stirring according to ISO 3632-2
      standard). The percentage of methanol, the sonication duration and duty cycles
      combination that can be recommended as optimum for the recovery of crocins and
      picrocrocin were 50%, 30 min, 0.2s and 0.44%, 30 min, 0.6s, respectively.
      Picrocrocin levels were not influenced dramatically under the optimum conditions
      for crocins extraction (11+/-2 instead of 12+/-1 mg kg(-1) dry stigmas,
      respectively) so that these can be considered optimum for both categories of
      tested compounds. Ultrasound assisted extraction speeded up further recovery of
      these precious apocarotenoids. Our findings for extraction conditions are useful
      for both industrial and analytical applications and should be considered in a
      forthcoming revision of the ISO 3632-2 technical standard.

PMID- 23146398
TI  - Measuring the molecular second hyperpolarizability in absorptive solutions by the
      third harmonic generation ratio technique.
AB  - Measurement of the second hyperpolarizability (gamma) values of compounds can
      provide insight into the molecular structural requirements for enhancement of
      third harmonic generation (THG) signal. A convenient method for measuring the
      gamma of compounds in solutions was developed by implementing the THG ratio
      method which is based on measuring the THG intensity from two interfaces using a
      nonlinear optical microscope while accounting for the refractive index of
      solutions at the fundamental and third harmonic wavelengths. We demonstrated that
      the difference in refractive index at both wavelengths strongly influenced the
      calculation of gamma values when compounds have absorption near the third
      harmonic or fundamental wavelength. To this end, a refractometer with the
      wavelength tuning range from UV to near IR was constructed, and the measured
      refractive indices were used to extract the gamma values. The gamma values of
      carotenoids and chlorophylls found in photosynthetic pigment-protein complexes
      were explored. Large differences in the refractive index at third harmonic and
      fundamental wavelengths for chlorophylls result in gamma values that are more
      than two orders of magnitude larger than gamma values for carotenoids as well as
      the sign of chlorophylls'gamma values is negative while carotenoids have positive
      gamma values.

PMID- 23146399
TI  - Liquid chromatographic determination of microcystins in water samples following
      pre-column excimer fluorescence derivatization with 4-(1-pyrene)butanoic acid
      hydrazide.
AB  - A method to measure the concentrations of microcystins (MCs) in water samples has
      been developed by incorporating pre-column fluorescence derivatization and liquid
      chromatography (LC). A solid-phase extraction for pretreatment was used to
      extract the MCs in water samples. The MCs were derivatized with excimer-forming 4
      (1-pyrene)butanoic acid hydrazide (PBH). The MCs could then be detected by
      fluorescence after separation with a pentafluorophenyl (PFP)-modified
      superficially porous (core shell) particle LC column. The derivatization
      reactions of MCs with PBH proceeded easily in the presence of 4,6-dimethoxy-1,3,5
      triazin-2-yl-4-methylmorpholinium (DMT-MM) as a condensation reagent, and the
      resulting derivatives could be easily separated on the PFP column. The
      derivatives were selectively detected at excimer fluorescence wavelengths (440
      540 nm). The instrument detection limit and the instrument quantification limit
      of the MCs standards were 0.4-1.2 MUg L(-1) and 1.4-3.9 MUg L(-1), respectively.
      The method was validated at 0.1 and 1.0 MUg L(-1) levels in tap and pond water
      samples, and the recovery of MCs was between 67 and 101% with a relative standard
      deviation of 11%. The proposed method can be used to quantify trace amounts of
      MCs in water samples.

PMID- 23146400
TI  - Modification of polypyrrole nanowires array with platinum nanoparticles and
      glucose oxidase for fabrication of a novel glucose biosensor.
AB  - A novel glucose biosensor, based on the modification of well-aligned polypyrrole
      nanowires array (PPyNWA) with Pt nanoparticles (PtNPs) and subsequent surface
      adsorption of glucose oxidase (GOx), is described. The distinct differences in
      the electrochemical properties of PPyNWA-GOx, PPyNWA-PtNPs, and PPyNWA-PtNPs-GOx
      electrodes were revealed by cyclic voltammetry. In particular, the results
      obtained for PPyNWA-PtNPs-GOx biosensor showed evidence of direct electron
      transfer due mainly to modification with PtNPs. Optimum fabrication of the PPyNWA
      PtNPs-GOx biosensor for both potentiometric and amperometric detection of glucose
      were achieved with 0.2 M pyrrole, applied current density of 0.1 mA cm(-2),
      polymerization time of 600 s, cyclic deposition of PtNPs from -200 mV to 200 mV,
      scan rate of 50 mV s(-1), and 20 cycles. A sensitivity of 40.5 mV/decade and a
      linear range of 10 MUM to 1000 MUM (R(2)=0.9936) were achieved for potentiometric
      detection, while for amperometric detection a sensitivity of 34.7 MUA cm(-2) mM(
      1) at an applied potential of 700 mV and a linear range of 0.1-9 mM (R(2)=0.9977)
      were achieved. In terms of achievable detection limit, potentiometric detection
      achieved 5.6 MUM of glucose, while amperometric detection achieved 27.7 MUM.

PMID- 23146401
TI  - Sensitive and simultaneous detection of different disease markers using
      multiplexed gold nanorods.
AB  - A multiplexed bioanalytical assay is produced by incorporating two types of gold
      nanorods (GNRs). Besides retaining the desirable features of common GNRs LSPR
      sensors, this sensor is easy to fabricate and requires only a visible-NIR
      spectrometer for detection. This assay can simultaneously detect different
      acceptor-ligand pairs by choosing the proper GNRs possessing various LPWs in a
      wide detection wavelength range and can be developed into a high-throughput
      detection method. This bioanalytical assay allows easy detection of human serum
      specimens infected by S. japonicum and tuberculosis (TB) from human serum
      specimens (human serum/Tris-HCl buffer ratio=1:10(4)) without the need for sample
      pretreatment. The technique is very sensitive compared to other standard methods
      such as indirect hemagglutination assays (IHA) that require a serum concentration
      ratio of larger than 1:20 and enzyme-linked immunosorbent assays (ELISA)
      requiring a ratio larger than 1:100. This methodology can be readily extended to
      other immunoassays to realize wider diagnostic applications.

PMID- 23146402
TI  - Separation of carboxylic acids in human serum by isotachophoresis using a
      commercial field-deployable analytical platform combined with in-house glass
      microfluidic chips.
AB  - Portable and field deployable analytical instruments are attractive in many
      fields including medical diagnostics, where point of care and on-site diagnostics
      systems capable of providing rapid quantitative results have the potential to
      vastly improve the productivity and the quality of medical care. Isotachophoresis
      (ITP) is a well known electrophoretic separation technique previously
      demonstrated as suitable for miniaturization in microfluidic chip format (chip
      ITP). In this work, a purpose-designed ITP chip compatible with a commercial end
      used targeted microfluidic system was used to study different injection protocols
      and to evaluate the effect of the length of the separation channel on the
      analytical performance. The in-house ITP chips were made from Corning glass and
      compared to the commercial DNA chip for the ITP separation of anions from the
      hydrodynamic injection of human serum. Using the in-house ITP chip the
      isotachophoretic step of lactate from human serum was approximately two times
      longer. The results of this research suggested that microfluidic ITP with
      indirect fluorescence detection is a viable technique for separation of organic
      acids in human serum samples, especially when a chip with suitable design is
      used.

PMID- 23146403
TI  - Proteomic identification of abnormally expressed proteins in early-stage placenta
      derived from cloned cat embryos.
AB  - It is unknown whether gene expression in cloned placenta during pre- and
      postimplantation is associated with early pregnancy failure in the cat. In this
      study, protein expression patterns were examined in early-stage (21-day-old)
      domestic cat placentas of fetuses derived from AI (CP; N = 4) and cloned embryo
      transfer (CEP; N = 2). Differentially expressed proteins were analyzed by two
      dimensional gel electrophoresis and matrix-assisted laser desorption/ionization
      time-of-flight (TOF) mass spectrometry (MS). A total of 21 proteins were
      aberrantly expressed (P < 0.05) by >1.5-fold in CEP compared with CP. Compared
      with CP, 12 proteins were upregulated in CEP (peptidyl-prolyl cis-trans isomerase
      A, annexin A2, protein DJ-1, adenylate kinase isoenzyme 1, protein disulfide
      isomerase A3, actin cytoplasmic 1, serum albumin, protein disulfide-isomerase A6,
      and triosephosphate isomerase), and nine proteins were downregulated
      (triosephosphate isomerase; heterogeneous nuclear ribonucleoprotein H;
      tropomyosin alpha-4; triosephosphate isomerase 1; 60 kDa heat shock protein,
      mitochondrial; serum albumin; calumenin; keratin type 1; and prohibitin). The
      identities of the differentially expressed proteins were validated by peptide
      mass fingerprinting using matrix-assisted laser desorption/ionization-TOF/TOF
      MS/MS. The abnormally expressed proteins identified in this study might be
      associated with impaired development and dysfunction of CEP during early
      pregnancy. Abnormal protein expression might also induce fetal loss and
      contribute to failure to maintain pregnancy to term.

PMID- 23146404
TI  - Spectrum and potency of ceftaroline tested against leading pathogens causing
      community-acquired respiratory tract infections in Europe (2010).
AB  - Ceftaroline, the active metabolite of the prodrug ceftaroline fosamil, is a novel
      cephalosporin exhibiting in vitro bactericidal activity against Gram-positive
      organisms, including Streptococcus pneumoniae and methicillin-susceptible and 
      resistant Staphylococcus aureus, as well as common Gram-negative organisms. The
      objective of this study was to determine the spectrum and potency of ceftaroline
      against recent leading pathogens causing community-acquired respiratory tract
      infections (CARTI) isolated in Europe. A total of 1563 isolates from the 2010
      Assessing Worldwide Antimicrobial Resistance Evaluation (AWARE) Program were
      identified as CARTI pathogens by the infection type and/or specimen type recorded
      by the participating laboratory. Isolates were collected from patients in 52
      medical centers located in 19 European countries (including Israel and Turkey).
      Susceptibility testing for ceftaroline and commonly used antimicrobials was
      performed by Clinical and Laboratory Standards Institute (CLSI) broth
      microdilution methodology. Susceptibility interpretations for comparators were as
      published in CLSI and the European Committee on Antimicrobial Susceptibility
      Testing guidelines, and for ceftaroline US-FDA breakpoints were also applied.
      Ceftaroline was very active overall against 799 S. pneumoniae (MIC(50/90,) <=
      0.008/0.12 MUg/mL) and inhibited 100.0% of all isolates at a MIC <= 0.5 MUg/mL.
      Ceftaroline was very potent against penicillin-resistant (CLSI oral penicillin V
      breakpoints) and -intermediate S. pneumoniae (MIC(50/90), 0.12/0.25 and 0.03/0.12
      MUg/mL, respectively), but potency was lower than observed against penicillin
      susceptible isolates (MIC(50/90), <= 0.008/<= 0.008 MUg/mL). Ceftaroline was also
      very active (MIC(50/90), <= 0.008/0.015 MUg/mL) against 515 Haemophilus
      influenzae, including beta-lactamase-producing strains (MIC(50/90), 0.015/0.06
      MUg/mL). Ceftaroline also demonstrated good activity against 205 Moraxella
      catarrhalis isolates (MIC(50/90), 0.06/0.12 MUg/mL). This study demonstrated the
      potent in vitro activity of ceftaroline against contemporary pathogens isolated
      from patients with documented CARTI from Europe. These data suggest that
      ceftaroline fosamil has an acceptable in vitro spectrum and potency against CARTI
      pathogens.

PMID- 23146405
TI  - Analysis of lymphocyte subsets in HIV-negative neurosyphilis patients.
AB  - It is unclear how Treponema pallidum affects the immune response among various
      lymphocyte subsets in neurosyphilis patients with different clinical stages. In
      order to determine the immune response by T. pallidum infection, we detected the
      peripheral blood lymphocyte subsets among 14 asymptomatic neurosyphilis patients,
      19 early neurosyphilis patients, 9 late neurosyphilis patients, and 50 healthy
      persons. The result indicated that the number of CD3+CD8+ lymphocytes was
      significantly higher in neurosyphilis patients than in the control group (chi(2)
      = 4.427, P = 0.035). The number of CD3+CD8+ lymphocytes was significantly higher
      in the asymptomatic neurosyphilis group than in the early neurosyphilis group,
      late neurosyphilis group, and control group (F = 4.644, P = 0.005). The number of
      NK cells was significantly lower in neurosyphilis patients than in the control
      group (chi(2) = 13.226, P = 0.000). The number of NK cells in neurosyphilis
      patients with different clinical stages was also lower than in the control group
      (F = 4.402, P = 0.006). The number of CD3+ lymphocytes, CD3+CD4+ lymphocytes, and
      B lymphocytes had no difference among the 4 groups. The results indicated that
      the progression of neurosyphilis may be related to the continued reduction in the
      number of NK cells and to the continued increase in CD3+CD8+ lymphocytes.

PMID- 23146407
TI  - Homozygous deletions of cadherin genes in chondrosarcoma-an array comparative
      genomic hybridization study.
AB  - Chondrosarcoma is a malignant bone tumor that is often resistant to chemotherapy
      and radiotherapy. We applied high resolution oligonucleotide array comparative
      genomic hybridization to 46 tumor specimens from 44 patients with chondrosarcoma
      and identified several genes with potential importance for the development of
      chondrosarcoma. Several homozygous deletions were detected. The tumor suppressor
      genes CDKN2A and MTAP were each homozygously deleted in four of the cases, and
      the RB1 gene was homozygously deleted in one. Two homozygous deletions of MTAP
      did not affect CDKN2A. Deletions were also found to affect genes of the cadherin
      family, including CDH4 and CDH7, each of which had a targeted homozygous loss in
      one case, and CDH19, which had a targeted homozygous loss in two cases. Loss of
      the EXT1 and EXT2 genes was uncommon; EXT1 was homozygously deleted in none and
      EXT2 in two of the cases, and large heterozygous losses including EXT1 and/or
      EXT2 were seen in three cases. Targeted gains and amplifications affected the
      MYC, E2F3, CDK6, PDGFRA, KIT, and PDGFD genes in one case each. The data indicate
      that chondrosarcomas develop through a combination of genomic imbalances that
      often affect the RB1 signaling pathway. The inactivation of cadherin genes may
      also be critical in the pathogenesis of the tumor.

PMID- 23146406
TI  - In vivo and in vitro comparison of female and male nociceptors.
AB  - While it is generally accepted that women have lower pain thresholds for diverse
      forms of noxious stimuli, the mechanistic basis for this sexual dimorphism in
      nociceptive pain remains to be elucidated. We confirmed, in the rat, that females
      have lower cutaneous mechanical nociceptive thresholds and established a similar
      sexual dimorphism in muscle. To determine if a peripheral mechanism underlies
      this sexual dimorphism in pain threshold, we compared biophysical properties of
      cultured dorsal root ganglion (DRG) neurons that innervated the gastrocnemius
      muscle in female and male rats. DRG neurons from female rats, which innervated
      the gastrocnemius muscle, had a more hyperpolarized resting membrane potential.
      To determine if this was associated with a higher mechanical nociceptive
      threshold, in contradiction to our working hypothesis, we compared the function,
      in vivo, of nociceptive afferents innervating the gastrocnemius muscle in male
      and female rats. C-fiber nociceptors innervating muscle in female rats had higher
      mechanical thresholds than those in males. Other response characteristics of
      these nociceptors were not significantly different. Thus, both in vitro and in
      vivo electrophysiology experiments support the idea that lower mechanical
      nociceptive threshold in females may be due to sexual dimorphism in central
      nervous system mechanisms, a difference large enough to overcome an opposing
      difference in peripheral pain mechanisms. PERSPECTIVE: This article unifies in
      vivo and in vitro electrophysiology with behavioral data examining the
      differences in mechanical nociceptive threshold between male and female rats. The
      data provide a novel perspective on the peripheral and behavioral outcomes of
      noxious mechanical stimulation.

PMID- 23146408
TI  - Cognitive stimulation therapy (CST): neuropsychological mechanisms of change.
AB  - BACKGROUND: Cognitive stimulation therapy (CST) is an evidence-based psychosocial
      intervention for people with dementia consisting of 14 group sessions aiming to
      stimulate various areas of cognition. This study examined the effects of CST on
      specific cognitive domains and explored the neuropsychological processes
      underpinning any effects. METHODS: A total of 34 participants with mild to
      moderate dementia were included. A one-group pretest-posttest design was used.
      Participants completed a battery of neuropsychological tests in the week before
      and after the manualised seven-week CST programme. RESULTS: There were
      significant improvement pre- to post-CST group on measures of delayed verbal
      recall (WMS III logical memory subtest - delayed), visual memory (WMS III visual
      reproduction subtest - delayed), orientation (WMS III information and orientation
      subscale), and auditory comprehension (Token Test). There were no significant
      changes on measures of naming (Boston Naming Test-2), attention (Trail Making
      Test A/Digit Span), executive function (DKEFS verbal fluency/Trail Making Test
      B), praxis (WMS III visual reproduction - immediate) or on a general cognitive
      screen (MMSE). CONCLUSIONS: Memory, comprehension of syntax, and orientation
      appear to be the cognitive domains most impacted by CST. One hypothesis is that
      the language-based nature of CST enhances neural pathways responsible for
      processing of syntax, possibly also aiding verbal recall. Another is that the
      reduction in negative self-stereotypes due to the de-stigmatising effect of CST
      may impact on language and memory, domains that are the primary focus of CST.
      Further research is required to substantiate these hypotheses.

PMID- 23146409
TI  - MC4-R signaling within the nucleus accumbens shell, but not the lateral
      hypothalamus, modulates ethanol palatability in rats.
AB  - The Melanocortin (MC) system is one of the crucial neuropeptidergic systems that
      modulate energy balance. The roles of endogenous MC and MC-4 receptor (MC4-R)
      signaling within the hypothalamus in the control of homeostatic aspects of
      feeding are well established. Additional evidence points to a key role for the
      central MC system in ethanol consumption. Recently, we have shown that nucleus
      accumbens (NAc), but not lateral hypothalamic (LH), infusion of a selective MC4-R
      agonist decreases ethanol consumption. Given that MC signaling might contribute
      to non-homeostatic aspects of feeding within limbic circuits, we assessed here
      whether MC4-R signaling within the NAc and the lateral hypothalamus (LH) alters
      normal ingestive hedonic and/or aversive responses to ethanol in rats as measured
      by a taste reactivity test. Adult male Sprague-Dawley rats were given NAc- or LH-
      bilateral infusion of the selective MC4-R agonist cyclo (NH-CH(2)-CH(2)-CO-His-D
      Phe-Arg-Trp-Glu)-NH(2) (0, 0.75 or 1.5MUg/0.5MUl/site) and following 30 min, the
      animals received 1 ml of ethanol solution (6% w/v) intraoral for 1 minute and
      aversive and hedonic behaviors were recorded. We found that NAc-, but not LH
      administration, of a selective MC4-R agonist decreased total duration of hedonic
      reactions and significantly increased aversive reactions relative to saline
      infused animals which support the hypothesis that MC signaling within the NAc may
      contribute to ethanol consumption by modulating non-homeostatic aspects
      (palatability) of intake.

PMID- 23146410
TI  - Safety of long-term isoniazid preventive therapy in children with HIV: a
      comparison of two dosing schedules.
AB  - SETTING: Two paediatric hospitals in Cape Town, South Africa. OBJECTIVE: To
      investigate the incidence of and risk factors for severe liver injury in human
      immunodeficiency virus (HIV) infected children receiving long-term isoniazid
      preventive therapy (IPT). DESIGN: Randomised  trial of IPT or placebo given daily
      or thrice weekly to HIV-infected children aged >=8 weeks; placebo was
      discontinued early. Alanine transaminase (ALT) was measured at baseline, 6
      monthly and during illness: an increase of >=10 times the upper limit of normal
      defined severe liver injury. RESULTS: Of 324 children enrolled, 297 (91.6%)
      received IPT (559.1 person-years [py]). Baseline median age was 23 months
      (interquartile range [IQR] 9.5-48.6) and median CD4%, 20% (IQR 13.6-26.9). A
      total of 207 (63.9%) children received combination antiretroviral therapy: 19
      developed severe  liver injury, 16 while receiving IPT. Among these there were 8
      cases of viral hepatitis (5 with hepatitis A), 2 antiretroviral-induced liver
      injuries and 1 case of abdominal tuberculosis. IPT-related severe liver injury
      occurred in 1.7% (5/297, 0.78/100 py). No child developed hepatic failure;  one
      died of an unrelated cause. All surviving children subsequently tolerated IPT.
      CONCLUSIONS: This study suggests that long-term IPT has a low toxicity risk in
      HIV-infected children. In the absence of chronic viral hepatitis, IPT can be
      safely re-introduced following recovery from liver  injury.

PMID- 23146411
TI  - Mitochondrial peroxidase TPx-2 is not essential in the blood and insect stages of
      Plasmodium berghei.
AB  - BACKGROUND: Malaria parasites actively proliferate in the body of their
      vertebrate and insect hosts, and are subjected to the toxic effects of reactive
      oxygen species. The antioxidant defenses of malaria parasites are considered to
      play essential roles in their survival and are thus considered promising targets
      for intervention. We sought to identify the cellular function of thioredoxin
      peroxidase-2 (TPx-2), which is expressed in the mitochondria, by disrupting the
      TPx-2 gene (pbtpx-2) of the rodent malaria parasite Plasmodium berghei. FINDINGS:
      In three independent experiments, two disruptant populations (TPx-2 KO) and three
      wild-type parasite populations with pyrimethamine resistance (dhfr-ts/mt at the
      DHFR-TS locus) and intact pbtpx-2 (TPx-2 WT) were obtained and cloned. Null
      expression of TPx-2 in the KO population was confirmed by RT-PCR and Western blot
      analyses. The TPx-2 KO parasite developed normally in mouse erythrocytes and
      multiplied at a rate similar to that of the TPx-2 WT parasite during the
      experimental period. The peak period of gametocytemia was delayed by 1 day in the
      TPx-2 KO compared with that of the TPx-2 WT and the parent parasite, however, the
      highest gametocyte number was comparable. The number of midgut oocysts in the TPx
      2 KO at 14 days post feeding was comparable to that of the TPx-2 WT. CONCLUSIONS:
      The present finding suggests that mitochondrial Prx TPx-2 is not essential for
      asexual and the insect stage development of the malaria parasite.

PMID- 23146412
TI  - RNA-based regulation of pluripotency.
AB  - Pluripotent cells have the unique ability to differentiate into diverse cell
      types. Over the past decade our understanding of the mechanisms underlying
      pluripotency, and particularly the role of transcriptional regulation, has
      increased dramatically. However, there is growing evidence for 'RNA-based'
      regulation of pluripotency. We use this term to describe control of gene
      expression by RNA-binding proteins (RBPs) and regulatory non-coding RNAs
      (ncRNAs). These molecules bind to specific elements within mRNAs and, by
      recruiting various effectors, affect many aspects of mRNA regulation. Here, we
      discuss the role of RBPs and ncRNAs in both the induction and maintenance of
      pluripotency. We highlight and contrast examples from pluripotent cell lines and
      in vivo systems while discussing the connection to transcriptional regulators.

PMID- 23146414
TI  - Development of reverse transcription loop-mediated isothermal amplification (RT
      LAMP) as a diagnostic tool of Toxoplasma gondii in pork.
AB  - A fast, sensitive and specific reverse transcription loop-mediated isothermal
      amplification (RT-LAMP) method for the detection of Toxoplasma gondii (T. gondii)
      in pork was developed. In this study, we used a conserved sequence of 18s rRNA of
      Toxoplasma gondii to design primers for RT-LAMP test. The amplication was able to
      finish in 60 min under isothermal condition at 63 degrees C by employing a set of
      six primers. The assay showed higher sensitivity than RT-PCR using T. gondii RNA
      as template. The RT-LAMP assay was also assessed for specificity and was found to
      precisely discriminate between positive and negative test samples. Furthermore,
      the assay correctly detected T. gondii from contaminated pork, and had the detect
      limit of 1 tachyzoite in 1g pork. This is the first report of a study which
      applied the RT-LAMP method to detect T. gondii from pork. As RT-LAMP requires
      very basic instruments and the results can be obtained by visual observation,
      this technique provides a simple and reliable tool for inspecting food which are
      T. gondii-contaminated.

PMID- 23146413
TI  - The association between early life and adult body mass index and physical
      activity with risk of non-Hodgkin lymphoma: impact of gender.
AB  - PURPOSE: To evaluate the association of body mass index (BMI) and physical
      activity (PA) during adulthood and at the age of 18 years with risk of non
      Hodgkin lymphoma (NHL). METHODS: We enrolled 950 newly diagnosed NHL patients and
      1146 frequency-matched clinic-based controls. Height, weight, and PA (recent
      adult and at the age of 18 years) were self-reported. Odds ratios (ORs), 95%
      confidence intervals, and tests for trend were estimated using unconditional
      logistic regression adjusted for age, gender, and residence. RESULTS: BMI at the
      age of 18 years was associated with an increased NHL risk (OR, 1.38 for highest
      vs. lowest quartile; p-trend = .0012), which on stratified analysis was specific
      to females (OR, 1.90; p-trend = .00025). There was no association of adult BMI
      with NHL risk. Higher PA in adulthood (OR, 1.03; p-trend = .85) or at the age of
      18 years (OR, 0.88; 95% confidence interval, 0.72-1.07) was not associated with
      risk, but there was an inverse association for adult PA that was specific to
      females (OR, 0.71; p-trend = .039). Only BMI at the age of 18 years remained
      significantly associated with NHL risk when modeled together with PA in adulthood
      or at the age of 18 years. There was little evidence for heterogeneity in these
      results for the common NHL subtypes. CONCLUSIONS: Early adult BMI may be of
      greatest relevance to NHL risk, particularly in females.

PMID- 23146415
TI  - In vitro ovicidal and larvicidal activity of Agave sisalana Perr. (sisal) on
      gastrointestinal nematodes of goats.
AB  - This study describes the in vitro anthelmintic activity of aqueous extracts (AE),
      ethyl acetate extracts (EE), flavonoid fractions (FF) and saponin fractions (SF)
      obtained from sisal waste (Agave sisalana) against gastrointestinal nematodes of
      goats. The activity of these extracts was evaluated by performing inhibition of
      egg hatch (EHA) and larval migration (LMI) assays. The EC(50) results of the EHA
      corresponded to 4.7, 0.1 and 0.05 mg/mL for EE, EA and FF, respectively. The SF
      fraction showed no ovicidal activity. The percent efficacies that were observed
      for the LMI were 50.3, 33.2 and 64.1% for the AE, EE and SF, respectively. The FF
      fraction did not show activity against the larvae. The analysis of the FF
      fraction indicates the presence of a homoisoflavonoid. This report suggests that
      the A. sisalana has activity in vitro against gastrointestinal nematodes of
      goats. This effect is likely related to the presence of homoisoflavonoid and
      saponin compounds, which have different actions for specific stages of nematode
      development.

PMID- 23146416
TI  - Effects of prospective-user factors and sign design features on guessability of
      pharmaceutical pictograms.
AB  - OBJECTIVE: To examine the associations between the guessing performance of 25
      pharmaceutical pictograms and five sign features for naive participants. The
      effect of prospective-user factors on guessing performance was also investigated.
      METHODS: A total of 160 Hong Kong Chinese people, drawn largely from a young
      student population, guessed the meanings of 25 pharmaceutical pictograms that
      were generally not familiar to them. Participants then completed a questionnaire
      about their drug buying and drug label reading habits, and their demographics and
      medication history. Finally they rated five features (familiarity, concreteness,
      complexity, meaningfulness, and semantic distance) of the pharmaceutical
      pictograms using 0-100 scales. RESULTS: For all pharmaceutical pictograms, mean
      and standard deviation of guessability score were 64.8 and 17.1, respectively.
      Prospective-user factors of 'occupation', 'age' and 'education level'
      significantly affected guessing performance. For sign features, semantic
      closeness was the best predictor of guessability score, followed by simplicity,
      concreteness, meaningfulness and familiarity. CONCLUSION: User characteristics
      and sign features are critical for pharmaceutical pictograms. To be effective,
      pharmaceutical pictograms should have obvious and direct connections with
      familiar things and it is recommended that pharmaceutical pictograms should be
      designed with consideration of the five sign features investigated here. PRACTICE
      IMPLICATIONS: This study provides useful information and recommendations to
      assist interface designers to create and evaluate icons for pharmaceutical
      products and to design more user-friendly pharmaceutical pictograms. However,
      further work is needed to see how older people respond to such pharmaceutical
      pictograms.

PMID- 23146417
TI  - Result and cost of hepatic chemoembolisation with drug eluting beads in 21
      patients.
AB  - PURPOSE: The aim of our study was to assess the results and cost of a treatment
      strategy involving transarterial chemoembolisation with drug eluting beads (DEB
      TACE) in patients with unresectable non-metastatic hepatocellular carcinoma
      (HCC). PATIENTS AND METHODS: This study included all patients treated with DEB
      TACE in our hospital between January 2009 and December 2010. All patients
      received DEB-TACE on demand and were evaluated after each session. RESULTS:
      Twenty-one patients received an average of 1.3 sessions. The median time to
      treatment discontinuation and median progression-free survival was 181 days and
      295 days, respectively. Toxicity caused treatment discontinuation in three
      patients (14%). For the hospital, the average direct cost of treatment was ?6,033
      according to the analytical accounting system vs. ?4,558 according to the
      official tariffs from the new French Diagnosis-Related Group prospective payment
      system (P=0.002). CONCLUSION: In the treatment of HCC, on-demand DEB-TACE
      stabilises the disease in some patients but has not yet been thoroughly
      evaluated.

PMID- 23146418
TI  - Ocular aberrations and visual function with multifocal versus single vision soft
      contact lenses.
AB  - PURPOSE: To investigate differences in ocular aberrations induced by centre-near
      multifocal soft contact lenses (SCL) relative to single vision SCLs and their
      effect on contrast sensitivity function (CSF). METHODS: Ocular aberrometry was
      measured in 18 cyclopleged subjects (19-24 years) while wearing Ciba Air Optix
      low (AOlow) and high (AOhigh) add, Bausch & Lomb PureVision low (PVlow) and high
      (PVhigh) add multifocals, and a Bausch & Lomb PureVision single vision (PVsv)
      control with the same -3.00 D distance back vertex power. Zernike polynomials
      were scaled to 4, 5 and 6 mm pupils. CSF was measured at equivalent distances of
      6 m, 1 m and 40 cm while fully corrected with spherical trial lenses at 6m.
      RESULTS: AOlow, AOhigh and PVhigh induced a negative shift in primary spherical
      aberration (Z12) from PVsv and all multifocal SCLs induced a positive shift in
      secondary spherical aberration (Z24) (all p<0.01), without significantly
      increasing coma. Area under the CSF (AUCSF) reduced at 40 cm for all multifocals
      relative to PVsv (p<0.05), but was not significantly different at 6 m or 1 m. A
      moderate correlation (r = -0.80, p<0.005) was found between changes in Z12 and
      AUCSF at 40 cm for AOhigh, with an increase in negative Z12 reducing multifocal
      induced loss of CSF. CONCLUSIONS: Centre-near multifocal SCLs induced a negative
      shift in Z12 and a positive shift in Z24. Although CSF was unaffected at 6 m and
      1m it was reduced at 40 cm, possibly because changes in Z12 and Z24 were not
      great enough to induce a significant shift in centre of focus and increase in
      depth of field.

PMID- 23146419
TI  - Complex visual hallucinations in a Parkinson patient: don't blame James if it's
      Charles's fault.
AB  - A patient with a history of Parkinson's disease and severe bilateral peripheral
      vision loss due to vitreous hemorrhages had complex visual hallucinations that
      persisted for three days and appeared every morning on awakening. The persistent
      nature of these hallucinations, the patient's preserved insight, and the presence
      of severe visual impairment was suggestive for Charles Bonnet syndrome rather
      than Parkinson-related hallucinations. A treatment with carbamazepine was started
      and proved to be successful. Physicians treating Parkinson patients should be
      familiar with Charles Bonnet syndrome and consider it as a potential alternative
      etiology for visual hallucinations, especially when the patient has severely
      impaired vision and when the hallucinations are sustained during wakefulness.

PMID- 23146420
TI  - Lung tumor segmentation in PET images using graph cuts.
AB  - The aim of segmentation of tumor regions in positron emission tomography (PET) is
      to provide more accurate measurements of tumor size and extension into adjacent
      structures, than is possible with visual assessment alone and hence improve
      patient management decisions. We propose a segmentation energy function for the
      graph cuts technique to improve lung tumor segmentation with PET. Our
      segmentation energy is based on an analysis of the tumor voxels in PET images
      combined with a standardized uptake value (SUV) cost function and a monotonic
      downhill SUV feature. The monotonic downhill feature avoids segmentation leakage
      into surrounding tissues with similar or higher PET tracer uptake than the tumor
      and the SUV cost function improves the boundary definition and also addresses
      situations where the lung tumor is heterogeneous. We evaluated the method in 42
      clinical PET volumes from patients with non-small cell lung cancer (NSCLC). Our
      method improves segmentation and performs better than region growing approaches,
      the watershed technique, fuzzy-c-means, region-based active contour and tumor
      customized downhill.

PMID- 23146421
TI  - Antiviral activity of punicalagin toward human enterovirus 71 in vitro and in
      vivo.
AB  - Human enterovirus 71 is one of the major causative agents of hand, foot and mouth
      disease in children and has caused mortalities in large-scale outbreaks in the
      Asia-Pacific region in recent years. No vaccine or antiviral therapy is available
      currently in the clinic. In this work, we investigated the antiviral effect of
      punicalagin on enterovirus 71 both in vitro and in vivo. The results showed that
      punicalagin reduced the viral cytopathic effect on rhabdomyosarcoma cells with an
      IC50) value of 15 MUg/ml. Moreover, punicalagin treatment of mice challenged with
      a lethal dose of enterovirus 71 resulted in a reduction of mortality and relieved
      clinical symptoms by inhibiting viral replication. Our work suggested that
      punicalagin have the potential for further development as antiviral agents
      against enterovirus 71.

PMID- 23146422
TI  - Synergism of three-drug combinations of sanguinarine and other plant secondary
      metabolites with digitonin and doxorubicin in multi-drug resistant cancer cells.
AB  - We determined the ability of some phytochemicals, including alkaloids (glaucine,
      harmine, and sanguinarine), phenolics (EGCG and thymol), and terpenoids (menthol,
      aromadendrene, beta-sitosterol-O-glucoside, and beta-carotene), alone or in
      combination with the saponin digitonin to reverse the relative multi-drug
      resistance of Caco-2 and CEM/ADR5000 cells to the chemotherapeutical agent
      doxorubicin. The IC(50) of doxorubicin in Caco-2 and CEM/ADR5000 was 4.22 and
      44.08MUM, respectively. Combination of non-toxic concentrations of individual
      secondary metabolite with doxorubicin synergistically sensitized Caco-2 and
      CEM/ADR5000 cells, and significantly enhanced the cytotoxicity of doxorubicin.
      Furthermore, three-drug combinations (secondary metabolite+digitonin+doxorubicin)
      were even more powerful. The best synergist was the benzophenanthridine alkaloid
      sanguinarine. It reduced the IC(50) value of doxorubicin 17.58-fold in two-drug
      combinations (sanguinarine+doxorubicin) and even 35.17-fold in three-drug
      combinations (sanguinarine+digitonin+doxorubicin) in Caco-2 cells. Thus
      synergistic drug combinations offer the possibility to enhance doxorubicin
      efficacy in chemotherapy.

PMID- 23146423
TI  - Malaria transmission after five years of vector control on Bioko Island,
      Equatorial Guinea.
AB  - BACKGROUND: Malaria is endemic with year-round transmission on Bioko Island. The
      Bioko Island Malaria Control Project (BIMCP) started in 2004 with the aim to
      reduce malaria transmission and to ultimately eliminate malaria. While the
      project has been successful in reducing overall malaria morbidity and mortality,
      foci of high malaria transmission still persist on the island. Results from the
      2009 entomological collections are reported here. METHODS: Human landing
      collections (HLC) and light trap collections (LTC) were carried out on Bioko
      Island, Equatorial Guinea in 2009. The HLCs were performed in three locations
      every second month and LTCs were carried out in 10 locations every second week.
      Molecular analyses were performed to identify species, detect sporozoites, and
      identify potential insecticide resistance alleles. RESULTS: The entomological
      inoculation rates (EIR) on Bioko Island ranged from 163 to 840, with the outdoor
      EIRs reaching > 900 infective mosquito bites per year. All three human landing
      collection sites on Bioko Island had an annual EIR exceeding the calculated
      African average of 121 infective bites per year. The highest recorded EIRs were
      in Punta Europa in northwestern Bioko Island with human biting rates of 92 and 66
      mosquito landings per person per night, outdoors and indoors, respectively.
      Overall, the propensity for mosquito biting on the island was significantly
      higher outdoors than indoors (p < 0.001). Both Anopheles gambiae s.s. and An.
      melas were responsible for malaria transmission on the island, but with different
      geographical distribution patterns. Sporozoite rates were the highest in An.
      gambiae s.s. populations ranging from 3.1% in Punta Europa and 5.7% in Riaba in
      the southeast. Only the L1014F (kdr-west) insecticide resistance mutation was
      detected on the island with frequencies ranging from 22-88% in An. gambiae s.s.
      No insecticide resistance alleles were detected in the An. melas populations.
      CONCLUSIONS: In spite of five years of extensive malaria control and a
      generalized reduction in the force of transmission, parasite prevalence and child
      mortality, foci of very high transmission persist on Bioko Island, particularly
      in the northwestern Punta Europa area. This area is favorable for anopheline
      mosquito breeding; human biting rates are high, and the EIRs are among the
      highest ever recorded. Both vector species collected in the study have a
      propensity to bite outdoors more frequently than indoors. Despite current vector
      control efforts mosquito densities remain high in such foci of high malaria
      transmission. To further reduce transmission, indoor residual spraying (IRS)
      needs to be supplemented with additional vector control interventions.

PMID- 23146425
TI  - Mortality in patients with premature lower extremity atherosclerosis.
AB  - OBJECTIVE: Lower extremity peripheral artery disease occurs mostly in the elderly
      and is associated with high mortality. Limited data are available regarding long
      term mortality in patients with premature lower extremity atherosclerosis (PLEA).
      Our objective was to determine the all-cause mortality and its predictors in
      younger PLEA patients. METHODS: We studied patients with severe PLEA who were <55
      years of age at diagnosis and treated at a single academic vascular center
      between 1998 and 2010. Data were collected prospectively at the initial
      evaluation for vascular care. National Death Index and hospital records were used
      to determine all-cause mortality. Demographic and clinical characteristics were
      summarized using count (%), mean (standard deviation), or median (interquartile
      range), and associations with aspirin use were tested using chi2 test, t-test, or
      Wilcoxon test. Survival times were estimated using Kaplan-Meier estimates, and
      associations with covariates were tested using simple and multivariable Cox
      proportional hazards models. RESULTS: A total of 564 patients were analyzed (46%
      female; 20% nonwhite; mean age 49.4 [6.4] years). Ninety-five percent of patients
      had >=2 cardiovascular risk factors, 31% had coronary artery disease (CAD), and
      10% had a history of cancer. During median follow-up of 5.6 years (interquartile
      range, 2.3-8.3 years), 108 deaths (19%) were recorded. Two-year estimated
      mortality (standard error) was 6% (0.01), and 5-year estimated mortality was 16%
      (0.02). In univariate regression analysis, patient age (P=.04), prior amputation
      (P<.01), history of cancer (P=.03), and established CAD (P=.04) were associated
      with increased risk of mortality. Aspirin use and lipid-lowering therapy at the
      time of first evaluation were associated with improved survival (P<.01 and P=.02,
      respectively). A multivariable Cox proportional hazards model identified age
      (hazard ratio [HR] for 5-year increase, 1.17; 95% CI, 1.01-1.36; P=.04), prior
      amputation (HR, 1.99; 95% CI, 1.18-3.34; P=.01), history of cancer (HR, 2.35; 95%
      CI, 1.36-4.07; P<.01), and CAD (HR, 1.76; 95% CI, 1.16-2.67; P<.01) as
      independent predictors of mortality in patients with PLEA. Importantly, history
      of aspirin use had a significant protective effect (HR, 0.45; 95% CI, 0.30-0.69;
      P<.01). The impact of lipid-lowering therapy was no longer significant in
      multivariable modeling. CONCLUSIONS: Patients with PLEA demonstrate high all
      cause mortality. No traditional cardiovascular risk factors predicted mortality.
      Aspirin therapy at the time of first evaluation was a significant and independent
      predictor of improved survival in patients with PLEA.

PMID- 23146426
TI  - Late neurological recovery of paraplegia after endovascular repair of an infected
      thoracic aortic aneurysm.
AB  - Spinal cord ischemia is a potentially devastating complication after thoracic
      endovascular aorta repair (TEVAR). Patients with spinal cord ischemia after TEVAR
      often develop paraplegia, which is considered irreversible, and have significant
      increased postoperative morbidity and mortality. We report the case of a patient
      with unusual late complete neurologic recovery of acute-onset paraplegia after
      TEVAR for an infected thoracic aortic aneurysm.

PMID- 23146427
TI  - Epidemiology and clinical significance of non-tuberculous mycobacteria isolated
      from pulmonary specimens.
AB  - SETTING: A tertiary university medical centre in northern Israel. OBJECTIVE: To
      evaluate the clinical significance of non-tuberculous mycobacteria (NTM) isolated
      from pulmonary specimens. DESIGN: Clinical and microbiological data were
      collected from patient files. Cases were classified  as definite, probable and
      possible NTM. RESULTS: Between 2004 and 2010, 215 cases with respiratory isolates
      of NTM were identified. Mycobacterium xenopi was the most common species (n = 84,
      39.1%), followed by M. simiae (n = 52, 24.2%). A total of 170 (79.1%)  cases were
      classified as possible and 24 (11.2%) as probable NTM. Only 21 (9.8%) cases were
      considered definite NTM, the majority of which were M. kansasii and M. avium
      complex. CONCLUSIONS: M. xenopi and M. simiae are the most prevalent species of
      NTM isolated  from respiratory samples in northern Israel. However, most of these
      isolates represent colonisation. Of the relatively small number of clinically
      significant isolates, M. kansasii and M. avium complex were the most common.

PMID- 23146428
TI  - Prognostic values of multichannel intraluminal impedance and pH monitoring in
      newborns with symptoms of gastroesophageal reflux disease.
AB  - OBJECTIVE: To evaluate the relationship between multichannel intraluminal
      impedance and pH monitoring (MII/pH) values in newborns with symptoms of
      gastroesophageal reflux disease (GERD) and clinical history in their first 3
      years of life. STUDY DESIGN: Sixty-four newborns with GERD symptoms who underwent
      MII/pH in the first weeks of life were enrolled into a clinical follow-up
      program. Follow-up visits were programmed at 1, 3, 6, 9, 12, 18, 24, and 36
      months. Patients were divided into 3 groups according to duration of symptoms:
      short (1-3 months), medium (4-9 months), and long (>9 months), and MII/pH values
      in these groups were compared. RESULTS: Fifty-three patients completed the 3-year
      follow-up. The number of patients with GERD symptoms decreased each month. A
      comparison of MII/pH values of the 3 lifetime symptom groups revealed differences
      in the impedance bolus exposure index (F = 83; P = .012) and proximal reflux
      frequency (F = 410; P = .022). These 2 MII variables showed an increasing trend
      from the short lifetime symptom group to the long lifetime symptom group. Weakly
      acidic reflux events, but not acidic events, were responsible for these
      differences. CONCLUSION: MII/pH in newborns has prognostic value regarding the
      duration of GERD symptoms and provides useful information that clinicians may
      give parents about the prognosis of symptomatic infants. Impedance bolus exposure
      index and proximal reflux frequency seem to be the variables with the highest
      predictive value. Weakly acidic reflux events play an important role in
      determining the duration of GERD symptoms in newborns.

PMID- 23146429
TI  - Short imidazolium chains effectively clear fungal biofilm in keratitis treatment.
AB  - Fungal keratitis is a leading cause of ocular morbidity throughout the world.
      However, current therapies against fungal keratitis are often ineffective.
      Herein, we have developed the amphiphilic main-chain imidazolium polymer (PIM-45)
      and oligomer (IBN-1) materials that can efficiently inhibit the growth of fungi
      with low minimal inhibition concentration (MIC) values and clear the fungal
      biofilm, while displaying minimal hemolysis. In vivo keratitis treatment
      indicates that topical solutions of these polyimidazolium salts (PIMSs) are safe
      and as effective as that of amphotericin B, the most commonly used agent for the
      treatment of Candida albicans (C. albicans) keratitis. Compared to the costly and
      unstable amphotericin B and fluconazole, PIM-45 and IBN-1 are easy to prepare,
      inexpensive and stable. They can be stored in phosphate-buffered saline (PBS)
      solutions with long shelf life for routine topical use.

PMID- 23146431
TI  - The use of fluorescent indoline dyes for side population analysis.
AB  - Dye efflux assay evaluated by flow cytometry is useful for stem cell studies. The
      side population (SP) cells, characterized by the capacity to efflux Hoechst 33342
      dye, have been shown to be enriched for hematopoietic stem cells (HSCs) in bone
      marrow. In addition, SP cells are isolated from various tissues and cell lines,
      and are also potential candidates for cancer stem cells. However, ultra violet
      (UV) light, which is not common for every flow cytometer, is required to excite
      Hoechst 33342. Here we showed that a fluorescent indoline dye ZMB793 can be
      excited by 488-nm laser, equipped in almost all the modern flow cytometers, and
      ZMB793-excluding cells showed SP phenotype. HSCs were exclusively enriched in the
      ZMB793-excluding cells, while ZMB793 was localized in cytosol of bone marrow
      lineage cells. The efflux of ZMB793 dye was mediated by ATP binding cassette
      (ABC) transporter Abcg2. Moreover, staining properties were affected by the side
      chain structure of the dyes. These data indicate that the fluorescent dye ZMB793
      could be used for the SP cell analysis.

PMID- 23146430
TI  - Formulations for trans-tympanic antibiotic delivery.
AB  - We have developed a drug delivery system for prolonged trans-tympanic antibiotic
      delivery from a single dose administration. Increased permeability to
      ciprofloxacin of the intact tympanic membrane (TM) was achieved by chemical
      permeation enhancers (CPEs--bupivacaine, limonene, sodium dodecyl sulfate); this
      was also seen by CPEs contained within a hydrogel (poloxamer 407) to maintain the
      formulation at the TM. The CPE-hydrogel formulation had minimal effects on
      auditory thresholds and tissue response in vivo. CPE-hydrogel formulations have
      potential for ototopical delivery of ciprofloxacin for the treatment of acute
      otitis media (AOM) and other middle ear diseases.

PMID- 23146432
TI  - The effect of artificial lipid envelopment of Adenovirus 5 (Ad5) on liver de
      targeting and hepatotoxicity.
AB  - Human Adenovirus type 5 (Ad5) has been extensively explored in clinical gene
      therapy, but its immunogenicity dramatically affects the kinetics and toxicity
      profile of the vector. We previously designed a variety of artificial lipid
      bilayer envelopes around the viral capsid to develop safer hybrid vectors. Here,
      we studied the interaction of enveloped Ad in cationic (DOTAP:Chol) or anionic
      (DOPE:CHEMS) lipid bilayers with different blood components. When Ad was
      enveloped by cationic lipids, significantly high levels of viral uptake in HepG2
      cultured cells were achieved, independent of blood coagulation factors present.
      In vitro experiments also showed that artificial envelopment of Ad completely
      altered the affinity towards both human and murine red blood cells. After
      intravenous administration in BALB/c mice, real-time PCR and transgene expression
      studies indicated that cationic lipid envelopes significantly reduced hepatocyte
      transduction significantly increasing virus lung accumulation compared to
      DOPE:CHEMS enveloped or naked Ad. ALT/AST serum levels and liver histology showed
      that envelopment also improved hepatotoxicity profiles compared to naked Ad. This
      study suggests that artificial envelopes for Ad significantly alter the
      interactions with blood components and can divert viral particles from their
      natural liver tropism resulting in reduced hepatotoxicity.

PMID- 23146433
TI  - Electrospun fibro-porous polyurethane coatings for implantable glucose
      biosensors.
AB  - This study reports methods for coating miniature implantable glucose biosensors
      with electrospun polyurethane (PU) membranes, their effects on sensor function
      and efficacy as mass-transport limiting membranes. For electrospinning fibres
      directly on sensor surface, both static and dynamic collector systems, were
      designed and tested. Optimum collector configurations were first ascertained by
      FEA modelling. Both static and dynamic collectors allowed complete covering of
      sensors, but it was the dynamic collector that produced uniform fibro-porous PU
      coatings around miniature ellipsoid biosensors. The coatings had random fibre
      orientation and their uniform thickness increased linearly with increasing
      electrospinning time. The effects of coatings having an even spread of submicron
      fibre diameters and sub-100 MUm thicknesses on glucose biosensor function were
      investigated. Increasing thickness and fibre diameters caused a statistically
      insignificant decrease in sensor sensitivity for the tested electrospun coatings.
      The sensors' linearity for the glucose detection range of 2-30 mM remained
      unaffected. The electrospun coatings also functioned as mass-transport limiting
      membranes by significantly increasing the linearity, replacing traditional epoxy
      PU outer coating. To conclude, electrospun coatings, having controllable fibro
      porous structure and thicknesses, on miniature ellipsoid glucose biosensors were
      demonstrated to have minimal effect on pre-implantation sensitivity and also to
      have mass-transport limiting ability.

PMID- 23146434
TI  - F3 peptide-functionalized PEG-PLA nanoparticles co-administrated with tLyp-1
      peptide for anti-glioma drug delivery.
AB  - The development of a drug delivery strategy which can mediate efficient tumor
      targeting together with high cellular internalization and extensive vascular
      extravasation is essential and important for glioma treatment. To achieve this
      goal, F3 peptide that specifically bind to nucleolin, which is highly expressed
      on the surface of both glioma cells and endothelial cells of glioma angiogenic
      blood vessels, is utilized to decorate a nanoparticulate drug delivery system to
      realize glioma cell and neovasculature dual-targeting and efficient cellular
      internalization. Tumor homing and penetrating peptide, tLyp-1 peptide, which
      contains the motif of (R/K)XX(R/K) and specially binds to neuropilin is co
      administrated to improve the penetration of the nanoparticles across angiogenic
      vasculature into glioma parenchyma. The F3 conjugation via a maleimide-thiol
      coupling reaction was confirmed by XPS analysis with 1.03% nitrogen detected on
      the surface of the functionalized nanoparticles. Enhanced cellular interaction
      with C6 cells, improved penetration in 3D multicell tumor spheroids, and
      increased cytotoxicity of the loaded paclitaxel were achieved by the F3
      functionalized nanoparticles (F3-NP). Following co-administration with tLyp-1
      peptide, F3-NP displayed enhanced accumulation at the tumor site and deep
      penetration into the glioma parenchyma and achieved the longest survival in mice
      bearing intracranial C6 glioma. The findings here clearly indicated that the
      strategy by co-administrating a tumor homing and penetrating peptide with
      functionalized nanoparticles dual-targeting both glioma cells and neovasculature
      could significantly improve the anti-glioma drug delivery, which also hold a
      great promise for chemotherapy of other hard-to-cure cancers.

PMID- 23146435
TI  - Bone grafts engineered from human adipose-derived stem cells in dynamic 3D
      environments.
AB  - Modular tissue engineering (TE) is a promising alternative to overcome the limits
      in traditional TE. In the present study, adipose tissue derived stem cells (ADSC)
      laden microcarriers are used as building blocks (microtissues) that self-assemble
      into macrotissues in a bottom-up approach. These bone grafts were compared with a
      classical top-down approach (scaffolds). This concept was compared with bone
      marrow derived stem cells (BMSC) as cell source. Cells were immunophenotypically
      analyzed, followed by 2D/3D osteogenic differentiation in static/dynamic
      conditions. The bone graft quality was evaluated by (immuno)histochemistry and
      gene expression. After 6 weeks of dynamic culturing, scaffolds were highly
      colonized although not in the center and the osteogenic gene expression was
      higher in contrast to static cultures. A cell-to-microcarrier ratio of 5 * 10(6)
      cells-0.09 g microcarriers leaded to aggregate formation resulting in
      microtissues with subsequent macrotissue formation. ADSC/BMSC on scaffolds showed
      a downregulation of Runx2 and collagen I, demonstrating the end-stage, in
      contrary to microcarriers, where an upregulation of Runx2, collagen I together
      with BSP and osteocalcin was observed. This paper showed that high quality bone
      grafts (2 cm3) can be engineered in a bottom-up approach with cell-laden
      microcarriers.

PMID- 23146436
TI  - Rapamycin encapsulated in dual-responsive micelles for cancer therapy.
AB  - Rapamycin has been developed as a potential anticancer drug for treatment in
      rapamycin-sensitive cancer models, but its poor water solubility greatly hampers
      the application to cancer therapy. This study investigated the preparation,
      release profiles, uptake and in vitro/in vivo study of a dual-responsive micellar
      formulation of rapamycin. Rapamycin-loaded micelles (rapa-micelles) measured
      approximately ca. 150 nm with narrow size distribution and high stability in
      bovine serum albumin solution. It was shown that rapamycin could be loaded
      efficiently in mixed micelles up to a concentration of 1.8 mg/mL by a hot shock
      protocol. Rapamycin release kinetic studies demonstrated that this type of
      micellar system could be applied in physiological conditions under varied pH
      environments. Confocal and pH-topography imaging revealed a clear distribution of
      rapa-micelles, and visible intracellular pH changes which induced encapsulated
      rapamycin to be released and then induced autophagolysosome formation. In vivo
      tumor growth inhibition showed that rapa-micelles exhibited excellent antitumor
      activity and a high rate of apoptosis in HCT116 cancer cells. These results
      indicated that dual-responsive mixed micelles provided a suitable delivery system
      for the parenteral administration of drugs with poor water solubility, such as
      rapamycin, in cancer therapy.

PMID- 23146437
TI  - Simultaneous inhibition of metastasis and growth of breast cancer by co-delivery
      of twist shRNA and paclitaxel using pluronic P85-PEI/TPGS complex nanoparticles.
AB  - The metastasis of breast cancer is the leading cause of cancer death in women,
      and the lung is a common location of a secondary tumor that has metastasized from
      the primary source tumor. In this work, an attempt to simultaneously inhibit the
      metastasis and growth of tumor by co-delivering Twist shRNA (shTwi) and
      paclitaxel (PTX) using the conjugate of pluronic P85 (P85) and low molecular
      weight polyethyleneimine (PEI) (P85-PEI)/D-alpha-tocopheryl polyethylene glycol
      1000 succinate (TPGS) complex nanoparticles (PTPNs) was performed on metastatic
      4T1 breast cancer cell line and its pulmonary metastasis mice model. The
      experimental results demonstrated that PTPNs could effectively achieve cellular
      uptake and RNA interference. The down-regulation of Twist protein resulted in
      significant inhibitory effect of cell migration and invasion with the inhibition
      rate of 88.7% and 91.06%, respectively. The IC50 of PTPNs against 4T1 cells was
      63-fold lower than that of free PTX. The prolonged circulation and increased
      accumulation of PTX and shTwi in lung and tumor were observed in in vivo
      biodistribution. The in vivo antitumor efficacy showed that PTPNs could not only
      inhibit the in situ tumor growth effectively, but also completely restrict the
      pulmonary metastasis in 4T1 pulmonary metastatic mice model. Therefore, co
      delivering chemotherapy drugs with metastasis regulator by PTPNs to
      simultaneously inhibit metastasis and growth of tumor could achieve synergistic
      effect for the effective therapy of metastatic breast cancer.

PMID- 23146438
TI  - O-GlcNAc processing enzymes: catalytic mechanisms, substrate specificity, and
      enzyme regulation.
AB  - The addition of N-acetylglucosamine (GlcNAc) O-linked to serine and threonine
      residues of proteins is known as O-GlcNAc. This post-translational modification
      is found within multicellular eukaryotes on hundreds of nuclear and cytoplasmic
      proteins. O-GlcNAc transferase (OGT) installs O-GlcNAc onto target proteins and O
      GlcNAcase (OGA) removes O-GlcNAc. Their combined action makes O-GlcNAc reversible
      and serves to regulate cellular O-GlcNAc levels. Here I review select recent
      literature on the catalytic mechanism of these enzymes and studies on the
      molecular basis by which these enzymes identify and process their substrates.
      Molecular level understanding of how these enzymes work, and the basis for their
      specificity, should aid understanding how O-GlcNAc contributes to diverse
      cellular processes ranging from cellular signaling through to transcriptional
      regulation.

PMID- 23146439
TI  - Kinetic isotope effects for studying post-translational modifying enzymes.
AB  - The ongoing development of new experimental approaches for the measurement of
      isotope effects is improving our understanding of the physical and chemical
      changes that occur during biological catalysis. Biological catalysis involves
      numerous steps that include binding, conformational changes, chemical catalysis
      and product release. The critical points on the free energy surface for
      biologically catalyzed reactions include all bound intermediates and the
      intervening transition states. Isotope effects can be used to investigate both
      intermediate (equilibrium isotope effects) and transition state (kinetic isotope
      effects) structures along the reaction coordinate. This review details new
      techniques for measuring isotope effects and provides several examples of their
      use in solving transition state structures for post-translational modifying
      enzymes.

PMID- 23146441
TI  - A new program of kidney transplantation from donors after cardiac death in Spain.
AB  - Despite the high rate of kidney transplantation in Spain, a disparity still
      exists between the numbers of donors and waiting-list patients. Donors after
      circulatory death (DCD) have been propagated as a promising approach to reduce
      the donor kidney shortage. In Europe most of the countries use controlled DCD,
      but in Spain, mainly uncontrolled DCD are harvested and until 2010 at only four
      institutions. In January 2010, we began a program of donation after uncontrolled
      DCD (Maastricht type II; unsuccessful resuscitation). The aim of this
      observational study was to describe our preliminary results. The numbers of
      recovered and transplanted organs per DCD were 27. There were no cases of primary
      nonfunction, but delayed graft function was present in 85% of recipients. Despite
      this impairment, about 75% of patients reached a serum creatinine below 2 mg/dL
      in the second month, with 1-year graft and patient survivals of 85% and 100%.
      Although, our preliminary results with a not very long follow-up and small number
      of patients suggested that utilization of DCD should be expanded because this
      type of donor increases the number of cases and opportunities of end-stage renal
      disease patients to reduce the waiting times for transplantation.

PMID- 23146442
TI  - Economic impact of the introduction of machine perfusion preservation in a kidney
      transplantation program in the expanded donor era: cost-effectiveness assessment.
AB  - BACKGROUND: Kidney transplantations (KT) from expanded criteria donors (ECD) show
      a higher rate of delayed graft function (DGF) that increases postoperative costs
      because of the prolonged hospital stay as well as the needs for dialysis and
      additional diagnostic procedures. Hypothermic machine perfusion (MP) might be
      superior to cold storage (CS) to reduce the relative risks of DGF and primary
      nonfunction (PNF) as well as to increase 1-year graft survival. OBJECTIVE: The
      aim of the study was to determine the relative cost-effectiveness of two
      different storage methods: MP versus CS. METHODS: A probabilistic decision tree
      was developed to compare MP and CS as graft preservation methods. The structure
      of the model was populated by review of the literature and outcomes of KT from
      ECD in our center. The model estimated budget impact and incremental cost
      effectiveness ratio in terms of DGF and PNF cases. The cost comparison of methods
      for KT preservation included: hospitalization and intermediate care unit stay;
      post-KT dialysis; graft removal; immunosuppressive regimen; treatment of acute
      rejection episodes; as well as costs of preservation solutions and pulsatile
      preservation device or storage containers. RESULTS: Resource consumption for CS
      stratified by graft function varied from $8,159 for immediate graft function
      (IGF) recipients to $10,865 for DGF recipients to $25,933 for PNF recipients.
      Meanwhile, resource consumption for MP varied from $9,522 for IGF to $12,228 for
      DGF to $27,297 for PNF recipients. The main components of resource consumption
      were hospitalization stay (41.5%-53.9%); graft explantation (20.2%), and the need
      for dialysis (16.0%). The budget impact per patient for the introduction of MP
      was $505. However, the incremental cost-effectiveness ratio was $3,369 for each
      DGF- or PNF- saved case. CONCLUSIONS: The introduction of the MP preservation
      technology in a KT program form ECD is cost-effective in terms of savings for DGF
      and PNF cases.

PMID- 23146443
TI  - Perception of transplant coordinator regarding relatives' attitude toward tissue
      donation request.
AB  - INTRODUCTION: Family denials for tissue donation are higher than denials obtained
      after organ donation. OBJECTIVES: To find out families' perception toward tissue
      request as well as its relation with the degree of acceptance or denial.
      MATERIALS AND METHODS: Following the request for tissue donation (corneas or
      different tissues), a five closed-question survey was designed and immediately
      answered by the Transplant Coordinator. The main aim was to find out whether the
      request determined surprise, disapproval, understanding, knowledge, and immediacy
      in the decision-making process, as well as its relation with the decision to
      donate. RESULTS: Of 1751 surveys, 991 were answered and collected from 2009 to
      2011, which represents a 56% from the total. Data collected relate to families
      510 who donated and 481 who did not (P = NS). The fact of requesting corneas only
      or different tissues did not influence the answers. Surprise and disapproval
      variables significantly predicted refusal to donation (P = .000). CONCLUSIONS:
      Regardless the request type (corneas or multitissue) variables influencing the
      decision making when approaching families are expression of surprise and
      disapproval. Neither understanding the application nor existence of a prior
      approach to donation has any influence whatsoever in the decision-making process.

PMID- 23146444
TI  - Pretransplant donor-specific HLA antibodies detected by single antigen bead flow
      cytometry: risk factors and outcomes after kidney transplantation.
AB  - BACKGROUND: The clinical significance of pretransplant donor-specific antibodies
      (pre-Tx DSAs) detected by single antigen bead flow cytometry (SAB-FC) remains
      unclear. Our aim was to investigate the impact that pre-Tx DSAs detected by SAB
      FC have on the early and late clinical outcomes. PATIENTS AND METHODS: We
      retrospectively tested stored frozen pre-Tx sera from 222 deceased-donor kidney
      transplants performed between November 1997 and November 2006. All patients had a
      negative complement-dependent cytotoxicity (CDC) cross-match with the donor.
      Median follow up was 5.1 years. RESULTS: Twenty-two (10%) patients had pre-Tx HLA
      antibodies detected by CDC. Pre-Tx HLA antibodies were detected using SAB-FC in
      the sera of 46 (20.7%) patients; 36 (16.2%) of them presented pre-Tx DSAs, 18 had
      class I antibodies, 9 class II, and 9 patients presented both classes. Mean pre
      Tx DSA class I/II was 2360/1972 (MFI) mean fluorescence index in non CDC
      sensitized patients. Pre-Tx DSAs were associated with female sex, retransplants,
      and pretransplant transfusions. Patients with Pre-Tx DSAs more than 1000 MFI and
      negative CDC screening presented a higher percentage of delayed graft function
      (61.1% versus 38.9%), more episodes of acute vascular rejection (33.3% versus
      13.7%), and chronic rejection as the cause of allograft failure (22.2% versus
      9.7%) compared with non-pre-Tx DSAs patients. Five-year allograft survival was
      significantly worse in patients with pre-Tx DSA (68.5% versus 82%, P = .006) and
      in patients with pre-Tx DSA class II more than 1000 MFI (43% versus 82%, P =
      .009). We didn't find differences in patient survival. DISCUSSION: Pre-Tx DSAs
      detected by SAB-FC were more frequent in female recipients, and they were
      associated with acute vascular and chronic rejection and a poorer graft outcome.

PMID- 23146445
TI  - Efficacy of a hepatitis B vaccination schedule with two cycles of four double
      doses of conventional vaccine and four doses of adjuvanted vaccine in chronic
      kidney disease patients evaluated for renal transplantation.
AB  - INTRODUCTION: The response to hepatitis B (HB) vaccine remains suboptimal among
      chronic kidney disease patients. The aim of this study was to analyze the
      efficacy of a hepatitis B vaccination schedule with two 4-double doses of
      conventional vaccine and four doses of adjuvant vaccine in chronic kidney disease
      patients evaluated for renal transplantation. METHODS: In this prospective study,
      we recruited chronic kidney disease patients evaluated for renal transplantation
      to receive four 40-MUg doses of hepatitis B virus vaccine (0, 1, 2 and 6 months)
      and another four 40 MUg doses of hepatitis B virus vaccine and four 20 MUg doses
      of adjuvant vaccine if they were nonresponders. AntiHBs titers were analyzed
      before every vaccine dose and 1 month after the fourth dose. RESULTS: One hundred
      fifty-five patients were enrolled in the study. The response to the vaccination
      increased until the seventh dose: first dose, 5.4%; second, 29.5%; third, 66.7%;
      fourth, 75.9%; fifth, 83.3%; sixth, 87.3%; seventh, 92.5%; and eighth, 93.8%.
      AntiHBs titers after the first and second vaccination with Engerix were 10 to 99
      mIU/mL in the 12% and 7.7%, 100 to 999 mIU/mL in the 30.1%, and 46.2%, and 1000
      mIU/mL in the 34.9% and 15.4%, respectively. Fendrix was administrated in 6.2% of
      the patients and 75% of them obtained a response. AntiHBc-positive patients
      obtained a response with one vaccination cycle in the 71.4%. The response was
      influenced by age and was greater in women. Adverse events were found in 11.5% of
      the patients (inflammation and/or local pain), which were less frequent in men
      (8.9% versus 16.1%) and similar for both vaccines. CONCLUSION: The response to
      the hepatitis B vaccination with four double doses of conventional vaccine and
      revaccination with the same schedule and adjuvanted vaccine shows a high response
      rate in chronic kidney disease evaluated for renal transplantation.

PMID- 23146446
TI  - C1q-fixing human leukocyte antigen assay in immunized renal patients: correlation
      between Luminex SAB-C1q and SAB-IgG.
AB  - BACKGROUND: There is no consensus about the impact of thresholds of complement
      fixing antibody assays. Recently, a C1q-SAB assay has been developed to identify
      complement-fixing HLA antibodies with high sensitivity and specificity. Our aim
      was to determine the correlation between IgG single antigens beads (SAB) and C1q
      SAB assay results among patients on the renal waiting list. PATIENTS AND METHODS:
      Serum samples from immunized renal waiting list patients as well as negative and
      positive controls were valided by Luminex (LMX). These sera, which were positive
      for 166 antibody specificities, were tested for HLA class I in parallel by LMX
      IgG and LMX-C1q. RESULTS: Comparison of antibody detection revealed no
      correlation based on median fluorescent intensity (MFI), levels between the IgG
      SAB and the C1qSAB assay (P > .05). IgG-positive sera with MFIs as low as 700
      were able to fix C1q, whereas other sera with MFIs as high 14,500 did not.
      Furthermore, there appeared to be disparities in the profiles of class I antigens
      able to fix C1q-SAB. In our series, only 34% class I IgG SAB antibodies were also
      C1qSAB+. In several patients, we detected C1qSAB+ against IgGSAB- that was surely
      due to IgM antibodies. So, the C1qSAB assay detected IgM antibodies that fix
      complement. CONCLUSION: These data suggested that the C1q-SAB assay could be an
      important method to evaluate pretransplant virtual crossmatch and to define
      nonpermitted specificities (C1q-fixing) in kidney transplantation.

PMID- 23146447
TI  - High regulatory T-cell levels at 1 year posttransplantation predict long-term
      graft survival among kidney transplant recipients.
AB  - INTRODUCTION: Regulatory T cells (Tregs) have gained an important role in
      mechanisms of tolerance and protection against the transplant rejection. However,
      only limited retrospective data have shown a relationship between peripheral
      blood Tregs and better long-term graft survival. The purpose of the present study
      was to investigate prospectively circulating Treg levels and their association
      with long-term graft survival. METHODS: Ninety kidney transplant recipients
      underwent measurement of Treg levels in peripheral blood before as well as at 6
      months and 1 year posttransplantation. Receiver operating characteristic curves
      were applied to test the sensitivity and specificity of Treg levels to predict
      prognosis. RESULTS: Treg levels before transplantation correlated with those at 6
      months and 12 months posttransplantation (P < .001 and P = .002, respectively).
      Patients who maintained high Treg levels (above 70th percentile) at both 6 and 12
      months displayed better long-term graft survival at 4 and 5 years follow-up (P =
      .04 and P = .043 respectively). There was no effect on patient survival.
      CONCLUSION: Detection of high levels of peripheral blood Tregs was associated
      with better graft survival possibly using as a potential marker of prognosis.

PMID- 23146448
TI  - Liver transplantation without abdominal drainage.
AB  - This observational cohort compared 70 consecutive liver transplantations (OLT)
      with no intra-abdominal drain and 70 control subjects C with an intra-abdominal
      drain who were operated immediately prior to them. We sought to assess the impact
      of abdominal drainage on the diagnosis and prevention of early postoperative
      complications of hemoperitoneum, reinterventions, biliary leaks or percutaneous
      drainage. We assessed variables related to the recipient (age, indication,
      pretransplant ascites, body mass index, Model for End-stage Liver Disease score,
      and rejection episodes, to the donor (age, steatosis and, ischemia time) as well
      as intra- and postoperative factors (surgery time, blood product use, and
      coagulopathy). The endpoint was defined as the need for a reintervention,
      postoperative paracentesis, appearance/drainage of collections, as well as
      lengths of hospital and intensive care unit (ICU) stays. Postoperative ICU and in
      hospital stay were similar between the groups (3.6 versus 3.7 days and 12 versus
      14 days respectively). Six patients in the drainage group were reoperated due to
      hemoperitoneum, whereas it was one in the cohort without drainage. Three patients
      presented a biliary fistula, two in the group without drainage, and one in the
      drainage group. One patient in the drainage group required percutaneous drainage
      of an intra-abdominal collection. The need for postoperative paracentesis was
      greater among the group without drainage (30% versus 6%; P < .008) and among
      those with a preoperative ascites > 1000 mL (38%). Patients with drainage
      displayed a greater incidence of perihepatic hematomas upon ultrasound (50%
      versus 22%, P < .008) and required more postoperative blood products, especially
      plasma (P < .01). In conclusion, OLT without intra- abdominal drainage is safe
      and does not increase morbidity. It seems likely that drainage may be responsible
      for intra-abdominal hematomas and greater consumption of blood products.

PMID- 23146449
TI  - High-sensitivity troponin T levels in kidney transplant recipients.
AB  - Cardiovascular disease (CVD) is still the leading cause of death among kidney
      transplant recipients. Validated biomarkers are important to identify patients at
      high risk for cardiovascular events and mortality. Cardiac troponins are one of
      the best available prognostic markers in this clinical situation, especially in
      chronic kidney disease and kidney transplant (KT) patients. The recently appeared
      high-sensitivity immunoassay to measure troponin T (hsTnT) has not yet been
      widely studied in the transplant population. We designed a cross-sectional study
      to evaluate hsTnT levels among 177 stable, asymptomatic patients, including 44.1%
      (78) males of overall mean age of 56.14 +/- 14.25 years. Mean glomerular
      filtration rate estimated with the MDRD-4 (eGFR MDRD) formula was 48.93 +/- 26.46
      mL/min/1.73 m(2). Median hsTnT was 11 (interquartile range = 11-26) ng/L.
      Patients were classified according to their hsTnT levels: normal, below 14 ng/L
      (57.6%, n = 102 patients), and those with basally elevated levels. Upon
      univariate analysis, a significant association was found between higher hsTnT
      levels and several variables, including clinical features, such as age, sex or
      prior CVD; renal function indicators: creatinine, eGFR MDRD, and proteinuria;
      nutritional and inflammation markers: albumin, ferritin, and C-reactive protein;
      and several cardiac enzymes: creatine kinase myocardial band (CKMB), B-type
      natriuretic peptide, and its N-terminal fragment. A logistic regression model
      adjusted for age, sex, and variables significantly associated with higher hsTnT
      levels, showed that male gender, age, CKMB, and lower glomerular filtration rate
      to show independent relation to basally elevated levels of hsTnT among
      asymptomatic kidney transplant recipients.

PMID- 23146450
TI  - Monitoring of circulating antibodies in a renal transplantation population:
      preliminary results.
AB  - BACKGROUND: The presence of circulating antibodies (CA) against human leukocyte
      antigen (HLA) and major-histocompatibility-complex class I-related chain A (MICA)
      antigens has been associated with worse renal function and reduced kidney
      allograft survival. We sought to describe the presence of donor-specific anti-HLA
      antibodies, non-donor specific antibodies, and antibodies against MICA antigens
      among a cohort of renal transplant recipients with respect to their evolution
      effects on renal function and occurrence of an acute rejection episode (AR) after
      transplantation. METHODS: This prospective study of 22 renal transplant
      recipients of deceased donor kidneys underwent studies of antibodies before and 3
      months after grafting using Luminex technology. RESULTS: Ten patients (five men
      and five women) showed preexistent CA. Comparing patients with versus without
      preformed CA, we did not observe a significant difference in donor and recipient
      age or gender. Eight patients (80%) with CA had undergone induction treatment
      with anti-human-activated T-lymphocyte rabbit immunoglobulin and 2 (20%) with
      basiliximab. There were no differences between groups regarding the incidence of
      acute rejection episodes (ARE n = 3 each). There was one case of Banff grade IIB
      ARE in a patient without preexisting CA; the other episodes were low-grade
      cellular responses. There were no differences in other variables including cold
      ischemia time, HLA mismatches, panel-reactive antibody levels, number of
      transfusions, cytomegalovirus infection or renal function at discharge and 3
      months later. Retransplantation was the only factor associated with preformed CA.
      Retransplantation and preformed CA were associated with CA at 3 months after
      transplantation. CONCLUSIONS: CA monitoring is important for highly sensitized
      renal transplants, although our experience failed to show a difference in graft
      survival or renal function in the first 3 months' follow-up.

PMID- 23146451
TI  - Role of fibroblast growth factor 23 (FGF23) in the metabolism of phosphorus and
      calcium immediately after kidney transplantation.
AB  - INTRODUCTION: Persistence of inappropriately high serum levels of fibroblast
      growth factor-23 (FGF23), a recently discovered phosphaturic hormone, has been
      reported to play an important role in the pathogenesis of posttransplant
      hypophosphatemia. The aim of the present study was to evaluate FGF23 in the early
      posttransplant period and study the complex associations between FGF23,
      parathyroid hormone (PTH), 1,25(OH)(2) vitamin D, and phosphate in transplant
      patients. MATERIALS AND METHODS: We performed a cross-sectional observational
      study of 42 adult kidney recipients in the early posttransplant period (<6
      months). Fasting serum samples and 24-hour urine samples were collected during a
      routine follow-up outpatient visit. Serum creatinine, calcium, phosphate,
      magnesium and urinary creatinine, calcium, magnesium, and phosphate were measured
      using standard assays. We also studied concentrations of 25 hydroxyvitamin D,
      1,25(OH)(2) vitamin D, intact PTH, and circulating FGF23. RESULTS: Median values
      for the different parameters studied were as follows: 9.9 +/- 0.6 mg/dL,
      phosphatemia 3.3 +/- 0.7 mg/dL, estimated glomerular filtration rate (eGFR; 41.1
      +/- 14.0 mL/min, phosphate reabsorption rate 68.4% +/- 10.7%, PTH 94.5 ng/L (53.8
      199.5), calcitriol 33.0 pg/mL (24.0-44.1), calcidiol 27.3 ng/mL (17.0-38.0),
      FGF23 139 pg/mL (88-221), and calciuria 62.5 mg/d (40.3-101.3). The variables
      significantly associated with serum FGF23 levels were phosphate reabsorption rate
      (r = .493; P = .001), calcitriol (r = .399; P = .009), eGFR (r = .557; P < .001),
      PTH (0.349; P = .024). CONCLUSIONS: Elevated serum levels of FGF23 could explain
      the deficiency of calcitriol and elevated renal phosphorus wasting in the early
      posttransplant period. All treatments that can lead to increased serum phosphate
      levels (eg, oral medication or calcitriol) should be carefully evaluated, since
      increased phosphatemia could further stimulate secretion of FGF23 and prolong
      high phosphorus loss.

PMID- 23146452
TI  - Prediction of kidney transplant outcome by donor quality scoring systems:
      expanded criteria donor and deceased donor score.
AB  - Due to disparity between organ supply and demand, use of kidneys from suboptimal
      donors has become increasingly common. Several donor quality systems have been
      developed to identify kidneys with an increased risk for graft dysfunction and
      loss. The purpose of our study was to compare the utility of deceased donor score
      (DDS) and expanded criteria donor (ECD) status to predict kidney transplant
      outcomes in a single center. We analysed 280 deceased donor renal transplantation
      procedures, collecting data from the prospectively maintained institutional
      database. Kidney transplant outcome variable included delayed graft function, 1
      year glomerular filtration rate (GFR1y), and death-censored graft loss (DCGL).
      Kidneys were obtained from marginal donors in 45.7% of transplant recipients by
      DDS and in 24.9% by ECD. DDS-defined marginal donors suffered delayed graft
      function (DGF) more frequently than nonmarginal donors (40.8% vs 25.0%; P =
      .006), whereas ECD did not develop DGF at a greater rate. GFR1Y was significantly
      worse among patients receiving kidneys from marginal donors: DDS 40.3 +/- 12.9 vs
      57.7 +/- 19.4 mL/min/1.73 m(2) (P < .001) and ECD 39.4 +/- 14.1 vs 53.8 +/- 19.1
      mL/min/1.73 m(2) (P < .0001). The most severe donor category defined by DDS
      (grade D) showed an independently worse death-censored graft survival hazard rate
      [HR] 2.661, 95% confidence interval [CI], 1.076-6.582; P = .034). DDS and ECD
      scoring systems are based on donor information available at the time of
      transplantation that predict 1-year graft function. Moreover in our center, DDS
      was better to predict DGF and death-censored graft survival than ECD.

PMID- 23146453
TI  - Rate of long-term graft loss has fallen among kidney transplants from cadaveric
      donors.
AB  - First-year renal allograft survival has increased, but whether this is associated
      with improvement in the long term is controversial. We analyzed 1045 consecutive
      adult deceased donor kidney transplant recipients from 1986 to 2001, with a
      follow-up to 2011. The aim of this study was to compare the graft half-life and
      attrition rates stratified by year of transplant in patients who received the
      graft in the periods 1986 to 1995 versus 1996 to 2001. The graft half-life
      increased significantly in the second period (P = .000) and the rate of graft
      loss stratified per year of evolution fell in all the study periods (P = .0000).
      In addition, the study period 1996 to 2001 was significantly associated with a
      reduction in graft failure risk compared with 1986 to 1995 in the multivariate
      analysis (P = .005). In conclusion, both short- and long-term graft survival
      increased significantly at our center.

PMID- 23146454
TI  - Concordance of estimated glomerular filtration rates using Cockcroft-Gault
      modification of diet in renal disease, and chronic kidney disease epidemiology in
      renal transplant recipients.
AB  - INTRODUCTION: Various equations have been used to estimate the glomerular
      filtration rate (GFR) in renal patients, including kidney transplant recipients.
      Controversy exists concerning which equation is more precise to determine kidney
      failure. AIM: The aim of this study was to analyze the concordance (bias,
      variability, and exactness) of GFR estimated by the Modification of Diet in Renal
      Disease (MDRD4) and the Chronic Kidney Disease Epidemiology (CKD-EPI) equations
      using the Cockcroft-Gault (CG) method as the reference. MATERIAL AND METHODS:
      This observational, cross-sectional study included 153 clinically stable patients
      who underwent kidney transplantation between 2007 and 2009. The GFR was estimated
      at 12 months after the transplantation using the MDRD and CKP-EPI formula, using
      CG as the reference. RESULTS: The mean GFR for the various methods was as
      follows: CG = 65.6 +/- 23.3 mL/min/1.73 m(2), MDRD4 = 54.9 +/- 19.3 mL/min/1.73
      m(2), and CKD-EPI = 55.8 +/- 19.6 mL/min/1.73 m(2). Good correlations were found
      between CG-MDRD4 (r = 0.84; P < .001), CG-CKD-EPI (r = 0.87; P < .001), and MDRD4
      CKD-EPI (r = 0.98; P < .001). The analysis of concordance detected a bias (normal
      difference) of -10.6 +/- 12.7 versus -9.8 +/- 11.3 mL/min/1.73 m(2) (P = .006), a
      variability (percent difference) of 14.5 +/- 15.4% versus 13.6 +/- 14.5% (P =
      .031), and an exactness (P30) of 81.7% versus 86.9% (P < .001) of CG-MDRD4 versus
      CG-CKD-EPI, respectively. For a GFR >60 mL/min/1.73 m(2) the exactness was 75.3%
      versus 83.5% (P < .001) for CG-MDRD4 versus CG-CKD-EPI, and for a GFR <= 60
      mL/min/1.73 m(2) it was 89.7% versus 91.2% (P < .001). CONCLUSIONS: In our
      population the CKD-EPI method most approached the CG values, particularly when
      the GFR was >60 mL/min/1.73 m(2).

PMID- 23146455
TI  - Renal function improvement after conversion to proliferation signal inhibitors
      during long-term follow-up in heart transplant recipients.
AB  - INTRODUCTION: The use of proliferation signal inhibitors (PSIs) for calcineurin
      inhibitor (CNI) minimization or conversion protocols has been promoted for heart
      transplantation (HT) in the contexts of renal insufficiency, cardiac allograft
      vasculopathy (CAV), or malignancy. We evaluated our experience with conversion of
      patients from a CNI-based to a PSI-based immunosuppressive regimen. We focused on
      improvement in renal function. METHODS: This prospective follow-up included 96 HT
      patients converted to a PSI-based regimen from 2001 to 2010. We evaluated changes
      in creatinine clearance (CrCl) prior to at 1 year and at the end of follow-up
      after conversion. RESULTS: Ninety-six patients including 86% men showed a mean
      age of 62 +/- 8 years. They were converted to a PSI-based regimen at 6.3 +/- 4
      years post-HT due to the following causes: CNI toxicity (45%), CAV (16%), cancer
      (16%), CNI toxicity + CAV (17%), or CNI toxicity + cancer (6%). CNI withdrawal
      was achieved in 77 cases (80%) and minimization in 19 (20%). Everolimus was used
      in 54 (56%) and sirolimus in 42 (44%) cases. Median follow-up time was 3.8 years.
      PSI discontinuation due to side effects was common (38%). There were 43 deaths
      mainly due to cancer and CAV. CrCl improved albeit not significantly in the
      withdrawal group from a median of 51 mL/min preconversion to 59 mL/min at the
      last follow-up (P = .12). In the minimization group, median CrCl worsened from a
      median of 61 mL/min preconversion to 51 mL/min at the last follow-up (P = .001).
      In the 58 cases (61%) of CNI nephrotoxicity, median CrCl improved from a median
      of 41 mL/min preconversion to 49 mL/min at the last follow-up (P = .04).
      CONCLUSION: Despite high rates of discontinuation of PSIs during long-term follow
      up, the conversion regimen seemed to be useful to diminish CNI-related renal
      insufficiency especially with CNI withdrawal.

PMID- 23146456
TI  - The effects of mineral metabolism markers on renal transplant outcomes.
AB  - BACKGROUND: Hyperparathyroidism is a common complication of chronic renal
      failure. A functioning kidney graft improves hyperparathyroidism but it can
      persist to some degree for years. Persistent hyperparathyroidism associated with
      hypercalcemia and hyperphosphatemia have been associated with poor graft and
      patient survivals. The purpose of the present work was to assess the association
      between calcium/phosphate mineral metabolism markers and graft outcomes. PATIENTS
      AND METHODS: Among 389 renal transplantations performed in our center between
      January 2000 and June 2008, 331 patients had functioning grafts at 12 months, the
      subjects of this study. Measurements of intact parathyroid hormone (iPTH), serum
      calcium and phosphate, tubular phosphate reabsorption, and urinary calcium
      excretion were performed at 1, 3, 6, and 12 months. The mean follow-up was 84.0
      +/- 31.8 months. RESULTS: During the follow-up period, 63 grafts (19.0%) were
      lost, 30 patients (9.0%) died, and 80 recipients (24.2%) presented at least one
      cardiovascular event. Univariate Cox proportional analysis showed high iPTH
      levels at 1 and 12 months after transplantation to not be associated with worse
      patient or graft survival or an higher risk of cardiovascular events. Serum
      phosphate and calcium concentrations as well as calcium-phosphate products during
      the first year after transplantation were not associated with graft and patient
      outcomes or cardiovascular events. However, serum calcium at 12 months showed an
      inverse association with graft survival after adjusting for other variables
      (hazard ratio 0.61; 95% confidence interval 0.40-0.94; P = .026). CONCLUSIONS:
      iPTH levels and serum phosphate concentrations and calcium-phosphate products
      during the first year after transplantation were not associated with graft
      outcomes. The inverse association between adjusted calcium and graft survival
      should be studied further.

PMID- 23146457
TI  - Initial immunosuppression with or without basiliximab: a comparative study.
AB  - BACKGROUND: Following liver transplantation, acute kidney injury (AKI) and
      chronic kidney disease occur in 20%-50% and 30%-90% of patients, respectively.
      Basiliximab, a chimeric monoclonal antibody, is highly effective to prevent
      rejection in organ transplant recipients, particularly among patients with renal
      dysfunction who benefit from delayed introduction of calcineurin inhibitors.
      OBJECTIVE: The objective of this study was to measure the immunosuppressive
      effect of basiliximab and its impact on renal failure, lengths of hospital and
      intensive care unit (ICU) stays and prevalence of infection. METHODS: From
      January 2010 through December 2011, we performed a controlled, nonrandomized
      study comparing two different immunosuppressive regimens: Group I, 36
      transplantation on 34 patients, tacrolimus and corticosteroids de novo with
      mycophenolate mofetil in cases of renal failure; and Group II, 33 transplantation
      in 33 patients, corticosteriods and mycophenolate mofetil de novo with
      basiliximab on day 0 and day 4, and inception of tacrolimus on day 3. RESULTS:
      Basiliximab patients (Group II) showed a significantly lower incidence of renal
      failure requiring replacement therapy (3.03% vs 25%; P = .014). The incidence of
      acute cellular rejection episodes treated with corticosteriod boluses was also
      significantly lower (3.03% vs 25%; P = .014). Bacterial, fungal, and
      cytomegalovirus infection rates were lower in Group II, although the differences
      were not significant. Similarly, Group II patients had an insignificantly shorter
      average stay in the hospital (25.9 vs 40.06 days) and the ICU (5.9 vs 8.17 days).
      CONCLUSIONS: Basiliximab administration with delayed introduction of calcineurin
      inhibitors may be an effective strategy to reduce post-liver transplantation AKI
      requiring renal replacement therapy.

PMID- 23146458
TI  - Relation of urinary gene expression of epithelial-mesenchymal transition markers
      with initial events and 1-year kidney graft function.
AB  - INTRODUCTION: Renal dysfunction due to acute rejection (AR), acute tubular
      necrosis, or calcineurin inhibitors toxicity is related to development of
      interstitial fibrosis/tubular atrophy (IF/TA) and graft survival. Determination
      of serum creatinine (sCr) displays poor sensitivity as a marker for early
      detection of graft dysfunction. Kidney biopsy is an accurate but invasive
      procedure for the diagnosis. The levels of urinary mRNA of genes that regulate
      epithelial-mesenchymal transition (EMT) can reflect early damage and detect the
      development of IF/TA. Repeated studies of these genes can provide noninvasive
      information about the evolution of the graft, facilitating early diagnosis and
      treatment. OBJECTIVE: To analyze the relationships between early and 1-year graft
      evolution in relation to gene expression of EMT biomarkers. METHODS: Seventy-one
      kidney transplant recipients were monitored during 1 year recording analytical,
      clinical, and histological (if available) data. We determined RNA gene expression
      of EMT, angiotensinogen, E-cadherin, N-cadherin, transforming growth factor (TGF)
      beta and bone morphogenetic patients 7 (BMP7). RESULTS: At 3 months,
      angiotensinogen (mean [standard deviation]), (2.42 [.66] versus 8.58 [3.24]; P =
      .017) and N-cadherin (0.59 [0.26] versus 3.15 [1.35]; P = .016) discriminate a
      good evolution from AR episodes BMP-7 discriminated a good evolution versus AR
      (0.72 [0.29] versus 4.53 [2.23]; P = .006) and delayed graft function versus AR
      (1.14 [0.79] versus 4.53 [2.23]; P = .049). After 1 year, the ratio TGF-beta/BMP7
      discriminated patients with an sCr > 1.5 mg/dL (6614.6 [1063.6] versus 3378.7
      [1019]; P = .034). There was a positive correlation between urinary and tissue
      TGF-beta [r = 59; P = .003]. CONCLUSION: The expression of studied genes
      reverting EMT at 3 months postransplantation showed differences in initial graft
      evolution. At 1 year, the TGF-beta/BMP7 ratio suggested activation of EMT,
      possible early marker of renal dysfunction.

PMID- 23146459
TI  - Mycophenolate mofetil and tacrolimus reduce mortality after deceased donor kidney
      transplantation.
AB  - A study of mortality in renal transplantation recipients showed that the
      combination of mycophenolate mofetil (MMF) and tacrolimus (TaC) reduced the
      mortality rate. We studied 1045 consecutive adult deceased donor kidney
      transplant recipients from 1986-2001, where follow-up to 2011 was a minimum of 10
      years, to analyze the impact of these immunosuppressive drugs on patient
      survival. Cox multivariate analysis showed that treatment with MMF and the use of
      TaC instead of cyclosporine reduced the risk of death by 43%. In conclusion, both
      immunosuppressive drugs reduced the risk of death of patients receiving from
      renal transplants deceased donors.

PMID- 23146460
TI  - Cardiovascular risk in recipients with kidney transplants from expanded criteria
      donors.
AB  - INTRODUCTION: Posttransplant cardiovascular disease (CVD) is the leading cause of
      death in renal transplant (RT) recipients and is more evident in recipients with
      transplants from expanded criteria donors (ECD). OBJECTIVES: We analyzed the
      evolution of cardiovascular risk factors and their association with patient
      mortality. MATERIALS AND METHODS: We undertook a single-center, prospective study
      of RT patients (n = 360) between 1999 and 2006. These were 180 recipients with
      transplants from ECD and 180 controls. We analyzed the baseline characteristics
      and the cardiovascular risk factors: hypertension, diabetes, dyslipidemia, CVD,
      and anemia. Posttransplant analyses included the evolution of cardiovascular risk
      factors and causes of death. RESULTS: The mean age of the ECD was 63.5 +/- 5.4
      versus 32.0 +/- 13.2 years in the non-ECD (P < .001) and the recipient ages were
      58.4 +/- 8.7 versus 40.8 +/- 13.3 years, respectively (P < .001). The median
      interquartile range [IQR] dialysis time was 25 months (15-39) versus 20 months
      (12-44; P = .017). The pretransplant body mass index was 26.89 +/- 3.91 versus
      25.43 +/- 4.72 kg/m(2) (P = .002); the median (IQR) number of antihypertensive
      drugs was two (1-2) versus two (1-2.75; P = .015); dyslipidemia was present in
      32.5% versus 21.6% (P = .024), diabetes in 10.6% versus 5.6% (P = .087), and CVD
      in 13.3% versus 7.8% (P = .086). Treatment with erythropoiesis-stimulating agents
      (ESA) was received by 84.9% versus 83.9% (P = .857). Concerning transplantation,
      the mean follow-up was 64.3 +/- 33.7 months. Hypertension was present at 3 and 5
      years in 85.6% versus 69.5% (P = .001) and 87.9% versus 72.8% (P = .009),
      respiratory. Treatment with angiotensin-converting enzyme inhibitors/angiotensin
      II receptor blockers at 3 and 5 years was 79.8% versus 64.5% and 85.6% versus
      65%. Dyslipidemia was present at 5 years in 63.1% versus 58.0% (P = .482). De
      novo diabetes occurred in 16.7% versus 11.1% (P = .128), and CVD in 13.5% versus
      4.5% (P = .003). Univariate and multivariate Cox regression proportional hazards
      models were constructed to analyze the factors associated with patient death.
      CONCLUSIONS: CVD is the most common cause of death in recipients of ECD, RT, 40%
      in the ECD group versus 28.6% in the control group. Tight control of
      cardiovascular risk factors and a good pretransplant patient selection
      contributed to the good results obtained.

PMID- 23146461
TI  - Long-term follow-up after conversion from tacrolimus to cyclosporin in renal
      transplant patients with new-onset diabetes mellitus after transplantation.
AB  - INTRODUCTION: The relationship between anticalcineurin (CNI) drugs and the
      development new-onset diabetes mellitus after kidney transplantation (NODAT) is
      well established. Among these agents cyclosporine shows lesser diabetogenicity
      than tacrolimus. It has been described that conversion from tacrolimus to
      cyclosporine improves glycemic control; however, there are no studies showing
      whether this reduced risk is maintained upon long-term follow-up. OBJECTIVE: To
      evaluate whether CNI drugs conversion from tacrolimus to cyclosporine helps to
      maintain better glycemic control. MATERIALS AND METHODS: We retrospectively
      evaluated the evolution of glucose metabolism at 5 years after conversion from
      tacrolimus to cyclosporine in eight patients (six men) with NODAT. Mean age was
      42.8 +/- 15 years, and time after transplantation to conversion 128 +/- 40
      months. We analyzed fasting serum glucose, lipid metabolism, renal function, and
      cyclosporine levels at 0, 6, 12, 24, 36, 48, and 60 months after conversion.
      RESULTS: At 6 months after conversion, improved glucose metabolism was observed
      (268 +/- 161 versus 121 +/- 31 mg/dL; P < .01) although it was minimal in one
      case with persistent high blood glycemic levels. Only two patients maintained a
      normal glucose at the end of follow-up. Five subjects showed increased glycemia
      at 12 to 24 months after conversion requiring antidiabetic therapy: three
      patients, insulin and two oral antidiabetic agents. Two patients lost their
      allografts due to chronic rejection at 32 and 50 months respectively. Among the
      other six patients, renal function remained stable (1.9 +/- 0.6 versus 2.11 +/-
      0.97 mg/dL; P = NS). There was no significant differences among the other
      variables. Cyclosporine levels remained stable during the follow-up. CONCLUSION:
      Conversion of renal transplant patients with NODAT from tacrolimus to
      cyclosporine improves glucose metabolism in the short term but glycemia increases
      thereafter.

PMID- 23146462
TI  - New-onset diabetes after transplantation: drug-related risk factors.
AB  - INTRODUCTION: New-onset diabetes after transplantation (NODAT), an important
      complication of renal transplantation leads to reduced graft function and
      increased patient morbidity and mortality. Because of its high incidence and
      immense impact on clinical outcomes, prevention of NODAT is highly desirable.
      Several modifiable and nonmodifiable risk factors for NODAT have been described.
      The aim of this study was to analyze the influence of various drugs on the
      development of NODAT during the first year. METHODS: A retrospective analysis was
      performed on 303 adult kidney transplant recipients free of previously known
      diabetes. NODAT was defined as a fasting plasma glucose level >= 126 mg/dL
      confirmed by repeat testing on a different day. We excluded patients with
      transiently elevated fasting plasma glucose during the first 3 months. RESULTS:
      NODAT was diagnosed in 37 recipients (12.2%). Univariate analysis identified
      several variables related to NODAT: recipient age (P < .001), body mass index (P
      < .001), donor age (P = .005), family history of diabetes (P < .001), statin use
      (P = .005), diuretic use (P = .040) and tacrolimus therapy (P = .029). After
      multivariate analysis, recipient age (relative risk [RR] = 1.060, 95% confidence
      interval [CI] 1.019- 1.102, P = .004), family history of diabetes (RR = 3.562,
      95% CI 1.574-8.058, P = .002), smoking habit (RR 2.514, 95% CI 1.118-5.655, P =
      .026) and diuretic use (RR = 2.496, 95% CI 1.087-5.733, P = .031) were
      independently associated with NODAT development. CONCLUSIONS: In our population
      of kidney transplant recipients, the main nonmodifiable risk factors for NODAT
      were recipient age and a family history of diabetes. Diuretic use was a
      modifiable risk factor associated with the development of NODAT. To reduce NODAT
      incidence, it is necessary to consider not only immunosuppressive therapy, but
      also concomitant drugs such as diuretics.

PMID- 23146463
TI  - Cinacalcet treatment for stable kidney transplantation patients with
      hypercalcemia due to persistent secondary hyperparathyroidism: a long-term follow
      up.
AB  - BACKGROUND: Cinacalcet is an effective treatment for hypercalcemia due to
      persistent hyperparathyroidism (HPT) in patients who have undergone kidney
      transplantation (KT). Few data are available about their long-term follow-up.
      OBJECTIVE: We aimed to evaluate the long-term efficacy of cinacalcet in
      functioning stable KT subjects with hypercalcemia secondary to persistent HPT.
      MATERIAL AND METHODS: Twenty-three patients (6 men) with a stable KT showed
      persistent hypercalcemia (>12 months) secondary to HPT (parathyroid hormone by
      radioimmunoassay [iPTH] > 150 pg/mL). The mean age was 54 +/- 13 years. Time
      after KT to beginning cinacalcet treatment was 36.5 +/- 37.9 (range 12 to 172)
      months. Initial cinacalcet doses were 30 mg/d. Median follow-up was 53 +/- 7.4
      months (range 42 to 60 months). We determined serum calcium, phosphorus, alkaline
      phosphatase, iPTH, creatinine, and immunosuppressant concentrations at baseline
      as well as 3, 6, and 12 months and after every 6 months thereafter. RESULTS:
      Initial serum calcium was 11 +/- 0.65 mg/dL and mean calcium during treatment,
      10.25 +/- 0.81 mg/dL (P < .001). Initial serum phosphorus was 2.8 +/- 0.58 mg/dL
      and mean value serum phosphorus during the treatment period, 3.13 +/- 0.6 mg/dL
      (P = 0.015). Initial iPTH was 260 +/- 132 pg/mL and during the treatment period;
      237 +/- 131 pg/mL (P = ns). There was no change in renal function nor in
      immunosuppressant blood levels. Doses of cinacalcet at the end of the follow-up
      were 40.4 +/- 18.9 mg/d. CONCLUSION: Cinacalcet was effective for long-term
      control of hypercalcemia related to persistent HPT for patients with stable KT.

PMID- 23146464
TI  - Anemia in kidney transplants without erythropoietic agents: levels of
      erythropoietin and iron parameters.
AB  - AIM: To study the association between hemoglobin, endogenous erythropoietin (EPO)
      levels and ferric parameters in kidney recipients not treated with EPO
      stimulating agents. MATERIALS AND METHODS: Transverse study of 219 kidney
      transplant outpatients. The median time after transplantation was 54 months (P(25
      75), 23-107). We assessed blood counts, ferric parameters, EPO levels, renal
      function (MDRD-4), and adjuvant treatment. We performed a linear regression
      analysis to predict hemoglobin. RESULTS: Median EPO values were 14.05 mUI/mL
      (P(25-75) = 10.2-19.7). Applying the formulas described by Beguin, kidney
      transplant recipients showed a low observed/expected ratio of erythropoietin and
      of transferrin. Considering anemia to be an hemoglobin of < 12 g/dL in women and
      < 13 g/dL in men, 24.2% of subjects were anemic (n = 53), including 2.3% with
      hemoglobin < 11 g/dL. Anemic patients displayed worse renal function (49.2 +/-
      18.5 versus 55.46 +/- 16.58 mL/min/1.73 m(2) in nonanemic; P = .021). There were
      no differences in C-reactive protein. The patients receiving a combination of
      angiotensin-converting enzyme inhibitors (ACEI) and angiotensin II receptor
      blockers (ARB) showed the highest prevalence of anemia compared with other groups
      (42.9%, P = .027). EPO levels were significantly lower among patients treated
      with these drugs (P = .041), without differences in transferrin and ferritin. The
      percentage of anemic patients treated with mammalian target of rapamycin
      inhibitors (mTORi) was 31% versus 22.2% among those not receiving these
      immunosuppressants (P = .23). Although there were no differences in hemoglobin
      levels, patients treated with mTORi, showed higher EPO levels (P = .005) and
      lower mean corpuscular volume (P < .001). Regarding the etiology of chronic
      kidney disease, less frequently anemic patients were those with polycystic kidney
      disease (8.6% versus 26.7% in the rest, P = .021). The formula obtained by
      multiple linear regression to calculate hemoglobin was: hemoglobin = 11829-0909
      log (EPG level) - 0455 (if female) + 0.010 0.013 transferrin + 0.013 creatinine
      clearance (r = .424, P < .001). CONCLUSIONS: Treatment with ACEI and/or ARBs
      seemed to produce a defect in the synthesis of EPO, while those treated with
      mTORi, a hyporesponsive state.

PMID- 23146465
TI  - Anemia at 1 year after kidney transplantation has a negative long-term impact on
      graft and patient outcomes.
AB  - BACKGROUND: Anemia, a common complication after kidney transplantation, has a
      controversial impact on graft or patient survivals or the appearance of
      cardiovascular disease. The present study investigated the incidence and risk
      factors for anemia in the first year after transplantation and its effects on
      graft and patient outcomes. PATIENTS AND METHODS: Among 389 patients transplanted
      between January 2000 and June 2008, the 331 with functioning grafts at 1 year
      were included in the study. The mean follow-up was 84 +/- 31.8 months. Anemia was
      defined according to the World Health Organization as a hemoglobin < 13 g/dL in
      men and < 12 g/dL in women. RESULTS: The 88 patients (26.6%) with anemia included
      21 (6.3%) who were receiving erythropoiesis stimulant agents. The predictive
      factors for anemia were: initial immunosuppression with cyclosporine (odds ratio
      [OR] 2.08, 95% confidence interval [CI] 1.25-3.47; P = .005), serum creatinine
      (mg/dL) at discharge (OR 1.7; CI 95% 1.26-2.15 P = .000), and 1-year serum
      albumin (g/dL; OR 0.21; CI 95% 0.10-0.71 P = .001). Donor age in years (OR 1.02;
      CI 95% 1.00-1.03, P = .054) was close to significance. Cox multivariate analysis
      showed 1-year hemoglobin (g/dL) to be associated with graft (hazard ratio [HR]
      0.81, 95% CI 0.69-0.96, P = .003) and patient survivals after adjusting for other
      variables (HR 0.74; 95% CI 0-59-0.96, P = .023). But it was only a cardiovascular
      risk factor when serum creatinine was not included in the model. CONCLUSIONS:
      Approximately one quarter of patients with functioning grafts show anemia at 1
      year. Graft function, initial immunosuppression, serum albumin, and perhaps donor
      age were risk factors for anemia, which had a negative impact on graft and
      patient survival, and could be a risk factor for cardiovascular disease.

PMID- 23146466
TI  - Effect of CYP3A51/3 polymorphism on blood pressure in renal transplant
      recipients.
AB  - BACKGROUND: The cytochrome P450 3A5 (CYP3A5) enzyme has been implicated to
      determine blood pressure (BP) in humans. Different results have been reported
      concerning CYP3A5 gene polymorphisms and posttransplantation hypertension in
      kidney recipients. Our objective was to investigate whether CYP3A5 1/3
      polymorphism was associated with ambulatory BP among a population of renal
      transplant recipients receiving the calcineurin inhibitor tacrolimus for
      immunosuppression. METHODS: Sixty primary kidney transplant recipients undergoing
      treatment with tacrolimus were genotyped for the CYP3A5 1/3 polymorphism. We
      analysed the association of the CYP3A5 alleles with ambulatory systolic and
      diastolic BP measured at 6 and 24 months posttransplantation. RESULTS: We
      observed that 23.3% of the patients were CYP3A5 1 carriers and 76.7% were
      homozygous for CYP3A5 3. CYP3A5 1 carriers showed higher adjusted systolic BP and
      diastolic BP at 6 and 24 months posttransplantation, and they were prescribed
      more antihypertensive drugs compared with non CYP3A5 1 carrier patients, albeit
      not significant. No significant differences were found comparing the distribution
      of the hypertension classes. CONCLUSION: We did not observe a significant
      association of CYP3A5 1/3 polymorphism with posttransplantation hypertension,
      although there were some differences in BP associated with the presence of the
      CYP3A5 1 allele.

PMID- 23146467
TI  - Transplant glomerulopathy: clinical course and factors relating to graft
      survival.
AB  - INTRODUCTION: Transplant glomerulopathy (TG) is usually associated with a poor
      prognosis for kidney graft survival. AIM AND METHODS: We analyzed 30 cases of TG
      diagnosed by kidney biopsy among a retrospective review of 579 biopsies performed
      between January 2006 and October 2011. RESULTS: At the time of biopsy, the mean
      glomerular filtration rate (GFR), estimated by the abbreviated Modification of
      Diet in Renal Disease was 31 +/- 10 mL/min and the proteinuria, 1.9 +/- 2 gr/24
      hours. Anti-human leukocyte antigen (HLA) antibodies were present in 40% of
      patients. The histological findings showed severe duplication of the glomerular
      basement membrane in 80% of patients; and interstitial fibrosis and tubular
      atrophy (IFTA) and moderate to severe arteriolar hyalinosis in 53% and 56%
      respectively. Fourteen patients lost their grafts. Graft survival was
      significantly associated with IFTA (P = .03) and renal function at the time of
      diagnosis (P = .03). CONCLUSIONS: TG was associated with a worse prognosis for
      the graft among kidney transplant patients. It is often associated with the
      presence of anti-HLA antibodies. Renal function at the time of diagnosis and IFTA
      were predictive factors for graft survival in these patients.

PMID- 23146468
TI  - Ambulatory blood pressure monitoring in kidney transplant patients: RETENAL
      study.
AB  - Hypertension is common following renal transplantation, affecting up to 80% of
      transplant recipients. It is generally accepted that hypertension is associated
      with poor graft survival and reduced life expectancy, contributing to increased
      cardiovascular risk factors and mortality rates. The aim of the study was to
      compare the blood pressure (BP) control in kidney transplant patients through the
      use of ambulatory BP monitoring (ABMP) versus office BP measurements (oBP). A
      multicenter, cross-sectional, observational study was conducted in 30
      nephrology/kidney transplant units. Eligible patients included hypertensive
      cadaveric kidney transplant recipients aged <70 years, with a functioning kidney
      for at least 1 year and with an estimated glomerular filtration >=30 mL/min/1.73
      m(2) and a serum creatinine < 2.5 mg/dL. Recorded data included demographic
      characteristics, oBP, and ABPM and labroatory investigations. The 868 patients
      showed a mean recipient age of was 53.2 +/- 11.6 years and mean follow-up after
      transplantation, 5.5 +/- 2.8 years. Mean systolic and diastolic oBP were 140.2 +/
      18 and 80.4 +/- 10 mm Hg, respectively. Seventy-six percent of patients had oBP
      higher than or equal to 130/80 mm Hg. Mean 24 hour ABPM were 131.5 +/- 14 and
      77.4 +/- 8.7 mm Hg for systolic and diastolic BP, respectively. Using the ABPM,
      we observed that 36.5% of subjects were controlled (mean 24-hour BP < 130/85 mm
      Hg). The two methods (oBP and ABPM) showed significant agreement. After ABPM, 65%
      of patients diagnosed as true controlled hypertension were considered to have
      white-coat RH. In clinical practice ABPM may help for better adjustment of drugs
      for adequate BP control.

PMID- 23146469
TI  - Efficacy of transjugular intrahepatic portosystemic shunt to prevent total portal
      vein thrombosis in cirrhotic patients awaiting for liver transplantation.
AB  - INTRODUCTION: Complete portal vein thrombosis (PVT) may complicate orthotopic
      liver transplantation (OLT), increasing its technical difficulty and the
      transfusion requirements and as well as affecting survival in some cases.
      Transjugular intrahepatic portosystemic shunt (TIPS) prevents total portal vein
      occlusion in patients with partial PVT. OBJECTIVE: We aimed to assess the
      efficacy and safety of TIPS to prevent total portal vein occlusion among patients
      listed for OLT. PATIENTS AND METHODS: We analyzed the clinical records of 15
      consecutive patients with partial PVT who underwent TIPS before OLT. The control
      group consisted of 8 transplanted patients without TIPS but partial PVT diagnosed
      before OLT. Portal vein patency at surgery, ischemia time, and transfusion
      requirements during OLT, and survival thereafter were compared between both
      groups. The main complications were also compared: mortality after TIPS (from
      TIPS placement to OLT), intraoperative technical complications, and technical
      complications during the 6 months after OLT. RESULTS: Clinical characteristics at
      the time of OLT were similar between the groups. No relevant complications were
      observed after TIPS; all patients underwent transplantation. One- and 5-year
      actuarial survival rates were similar in both groups (92% and 85% in TIPS-group
      versus 100 and 75% in the control group, respectively). No differences in
      transfusion requirement, duration of ischemia, and frequency of technical
      complications during and after OLT were observed between the groups. The portal
      vein was patent at surgery in all TIPS patients and 4 of 8 (50%) in the control
      group (P = .008). CONCLUSION: TIPS may prevent PVT in liver transplantation
      candidates with partial PVT.

PMID- 23146470
TI  - Incidence of hepatic artery variations in liver transplantation: does it really
      influence short- and long-term results?
AB  - BACKGROUND: Some variations of hepatic artery, which show 30% incidence, must be
      taken into account to avoid damage to the liver transplant during harvesting, we
      analyzed the incidence of variations and their influence on postoperative
      results. PATIENTS AND METHODS: We performed a retrospective study of 325 liver
      transplantation between 2001 and December 2011. RESULTS: Variations in the
      hepatic artery were detected in 91 transplantations (32%) including 29 donors
      (8.9%), 57 recipients (17.5%), and 5 both (1.5%). The main variation among donors
      was a right hepatic artery originating from the mesenteric artery (38.2%), and a
      left hepatic artery from the left gastric artery (35.3%). Recipients showed the
      same distribution: RHA-UMA (right hepatic artery from upper mesenteric artery)
      (38.7%) and LHA-LGA (left hepatic artery from left gastric artery) (12.9%). 48.5%
      of donor hepatic variations did not need bench reconstruction, but all RHA-UMA
      required it mainly due to the donor gastroduodenal artery (7; 58%) We did not
      observe significant difference in cold or warm ischemia time, surgical time, red
      blood cell requirement, postoperative mortality, or overall survival when there
      was or was not an arterial anomaly. But arterial complications were more frequent
      in cases where there were recipient anomalies or both versus without anomalies or
      with donor anomalies (20%, 7,8%, 0%, 5,6%; P = .06). Donor RHA-UMA was associated
      with worse overall survival (69, 2%; P = .07) and longer cold ischemia time and
      red blood requirement. Bench reconstruction held to longer cold ischemia time and
      blood cell requirements (P = .01) and shorter overall survival (82.4%). RHA-UMA
      was associated (P = .08) with worse actuarial survival and a needed for bench
      reconstruction (P = .01). CONCLUSION: One must be careful during liver harvest to
      detect hepatic artery variations to avoid damage. Hepatic artery anomalies do not
      influence liver transplant results except for the presence of an RHA from the UMA
      with a need for bench reconstruction.

PMID- 23146471
TI  - Comparison of quality of life between two clinical conditions with
      immunosuppressive therapy: liver transplantation and multiple sclerosis.
AB  - OBJECTIVE: We aimed to compare quality of life in two clinical conditions treated
      with immunosuppressants: cadaveric liver transplant recipients and multiple
      sclerosis patients. We also assessed the clinical significance of these results
      regarding a representative age-adjusted sample of the general Spanish population.
      METHODS: Using a cross-sectional design, the SF-36 Health Survey was used to
      evaluate 62 patients with these chronic conditions (31 in each group) who were
      matched for gender. An analysis of covariance was performed to control for the
      influence of time from multiple sclerosis diagnosis and liver transplantation
      surgery until assessment. Student t test of covariate-adjusted mean values was
      used as the statistical test and Cohen's d effect size index, to assess the
      magnitude of intergroup differences and assess clinical significance. RESULTS:
      Significantly worse scores were observed among the neurological patients compared
      with transplant recipients regarding role-physical (P = .038), general health (P
      = .003), vitality (P = .034), and physical functioning (P = .049), with medium
      effect sizes (Cohen's ds from -0.511 to -0.785). Against normative values, liver
      transplant recipients displayed relevant differences in all SF-36 subscales
      (Cohen's ds from -0.569 to -0.974) except for mental health (small effect size).
      Likewise, multiple sclerosis patients showed much greater differences versus the
      general population (Cohen's ds from -0.846 to -1.760). CONCLUSIONS: Liver
      transplant recipients showed better quality of life than multiple sclerosis
      patients (medium effect sizes) in physical quality-of-life dimensions.
      Interestingly, despite having controlled for time from diagnosis/transplantation,
      both medical conditions showed clinically significant impairments (large and
      medium effect sizes) in physical and psychosocial quality-of-life domains. We
      concluded that transplant recipients belong to a population that still requires
      special health care because, even after having undergone their treatment of
      choice, they do not achieve normal levels of biopsychosocial functioning.

PMID- 23146472
TI  - Biopsychosocial functioning in liver patients of alcoholic etiology as a function
      of self-perceived pain level.
AB  - OBJECTIVE: To compare the biopsychosocial functioning among liver transplantation
      and cirrhotic patients as a function of self-perceived pain level. METHODS: We
      selected two groups of liver patients of the same gender (men) and disease
      etiology (alcoholic): there were 39 liver transplant recipients and 34 severe
      cirrhotic patients. The Hospital Anxiety and Depression Scale and the SF-36
      Health Questionnaire were used. We applied analysis of covariance, with age and
      model end-stage liver disease (MELD) scores as covariates to assess the influence
      of two independent factors: (1) group (liver transplant recipients and cirrhotic
      patients), and (2) self-perception of pain (mild and high). We also calculated
      Cohen's d as an effect size index. RESULTS: No interactive effects were found
      between factors group and self-perceived pain in any of the variables studied.
      With regard to the main effects, we found statistically significant differences
      in the following variables between: a) liver transplant recipients and cirrhotic
      patients: anxiety (P = .000), depression (P = .003), role-physical (P = .001),
      mental health (P = .016), general health (P = .000), vitality (P = .000), and
      physical functioning (P = .000); and b) liver patients with mild and high self
      perceived pain: anxiety (P = .008), depression (P = .000), role-physical (P =
      .002), mental health (P = .000), vitality (P = .000), and physical functioning (P
      = .001). In all the indicated variables, with medium and large effect sizes
      (Cohen's ds from 0.58 to 1.64), the cirrhotic patients and patients with a high
      level of self-perceived pain had much poorer mental health and quality of life.
      CONCLUSION: Alcoholic cirrhotic male patients with a high level of self-perceived
      pain had the greatest biopsychosocial impairment, even exceeding the clinical
      threshold in the anxiety and depression scales; and the highest biopsychosocial
      well-being was associated with liver transplant recipients with a mild level of
      self-perceived pain.

PMID- 23146473
TI  - Coping strategies in liver patients as a function of relatives' anxiety level.
AB  - OBJECTIVE: To determine whether differences in the coping strategies used by
      liver patients during the pretransplantation phase were a function of their
      relatives' level of anxiety. MATERIALS AND METHODS: We assessed 75 pre-liver
      transplantation patients and 75 relatives (one per patient). To assess relatives'
      anxiety status, we used the Hospital Anxiety and Depression Scale (HADS), and the
      Questionnaire of Coping with Stress in Cancer Patients (CAEPO) to study patients'
      coping strategies. Three subgroups of relatives were established as a function of
      their scores on the HADS anxiety subscale: normal anxiety (G(1)), dubious anxiety
      (G2), and clinical anxiety (G(3)). To verify intergroup differences in the coping
      strategies used by the patients, we used the nonparametric Kruskal-Wallis H test.
      We also performed pairwise comparisons with nonparametric Mann-Whitney U test
      (with Bonferroni's correction) and Cohen's d as an effect size index. RESULTS:
      Focusing on the most relevant effect sizes, the pairwise contrasts indicated the
      following differences: a) normal anxiety (G(1)) and dubious anxiety (G(2)):
      seeking social support (d = 0.502); b) normal anxiety (G(1)) and clinical anxiety
      (G(3)): coping and active fighting (d = 0.607), self-control and emotional
      control (d = 0.658), and seeking social support (d = 0.944); and c) dubious
      anxiety (G(2)) and clinical anxiety (G(3)): coping and active fighting (d =
      0.743), self-control and emotional control (d = 0.722), and seeking social
      support (d = 0.515). CONCLUSION: In general, during the pre-liver transplantation
      study, the liver patients whose relatives showed clinical levels of anxiety used
      these three healthy coping strategies to a lesser extent: coping and active
      fighting, self-control and emotional control, and seeking social support.

PMID- 23146474
TI  - Affective status in liver transplant recipients as a function of self-perception
      of general health.
AB  - OBJECTIVE: We aimed to determine whether there were differences with regard to
      anxiety and depressive symptomatology between liver transplant recipients with
      better (G(1)) versus worse (G(2)) self-perceptions of general health compared
      with pre-liver transplantation cirrhotic patients (G(3)). METHODS: The groups of
      patients included 168 recipients including 85 and 83 with better or worse self
      perceptions of general health, respectively, and 75 cirrhotic pre-liver
      transplantation patients. For the psychological assessment we used the Hospital
      Anxiety and Depression Scale and the general health dimension of the SF-36 Health
      Questionnaire. The following analyses were used: Analysis of variance (ANOVA)
      with post hoc pairwise comparisons by means of Tukey's test and Cohen's d, an
      effect size index. RESULTS: Significant differences were observed among the three
      groups for the variables of anxiety (P = .000) and depression (P = .000).
      Specifically, liver transplant recipients with better self-perceptions of general
      health displayed lower scores (better mental health) compared with those showing
      worse self-perceptions or cirrhotic patients. There were no differences between
      the latter two groups. The differences in these variables were relevant (large
      effect sizes) for anxiety (Cohen's d(1-2) = -1.075, Cohen's d(1-3) = -1.155) and
      for depression (Cohen's d(1-2) = -1.145, Cohen's d(1-3) = -1.158). CONCLUSION:
      The anxious-depressive status was not necessarily better among liver transplant
      recipients. There was great variability among them as a function of self
      perceived general health. Transplant recipients with worse self-perception of
      general health presented the same anxiety-depressive levels as patients with
      severe liver disease in the pretransplantation phase; the latter groups reach the
      clinical threshold on the depression scale.

PMID- 23146475
TI  - Clinical value of a single determination of intracellular ATP levels in
      stimulated CD4+ T lymphocytes in pediatric patients with stable liver
      transplantation.
AB  - In the follow-up of transplanted patients under immunosupression, the functional
      assessment of CD4+ T cells activation by measuring intracellular ATP levels in
      vitro, using the Immuknow test give information on how immune system is
      functioning. Therefore, it has been reported that low levels of ATP correlate
      with the risk of opportunistic infection. Although limited, comprehensive results
      in adult recipients as well as in pediatric transplanted patients have been
      reported. Forty stable liver pediatric transplanted patients (mean age: 11.0
      years [SD 5.65]), within at least 1 year of transplant were selected for a
      scheduled review, and an unique determination of Immuknow was performed. Average
      ATP levels were 317 ng/mL (200-400 ng/mL) which were similar to the values
      observed in adult population. ATP values among patients with monotherapy
      Cyclosporin A (CSA) or tacrolimus (TAC) were significantly higher (P = .005) than
      in patients with double immunosupressive therapy using either CSA/TAC +
      Mycophenolate Mofetil (MMF). In CSA treatment, there are significant differences
      (P = .0003) between monotherapy and double therapy, but in the case of TAC we did
      not find differences (P > .1). A single determination of levels of ATP on CD4+
      lymphocytes, can provide additional information that could be used as a
      complementary test to guide immunosuppressive therapy in paediatric liver
      transplant recipients.

PMID- 23146476
TI  - Transplantation for acute liver failure: report of results in the region of
      Castilla y Leon (Spain) after 10 years of activity.
AB  - Acute liver failure is an uncommon disease but its overall mortality rate is
      still high without liver transplantation, which is the treatment of choice for
      patients achieving certain criteria. We have reported herein the experience and
      retrospectively analyzed results of liver transplantation for acute liver failure
      since the beginning of activity of our group, which is the only one in the region
      of "Castilla y Leon" (Spain). In 10 years, 14 patients underwent emergency
      transplantation among an overall series of 325 subjects. The patients were
      generally young men and women; the average wait list time was 2.14 days. The most
      common etiology was toxic exposure (no cases were related to acetaminophen
      overdose), followed by viral infection (all because of acute hepatitis B). Our
      posttransplant outcomes were: perioperative mortality, 0%; posttransplant in
      hospital mortality, 14%; and 1-y, 3-y, and 5-year survival rates of 77.1%, 64.3%,
      and 64.3% respectively. Retransplantation rate was 7%. A major morbidity occurred
      in four patients: one primary dysfunction, one hyperacute rejection due to ABO
      blood group-incompatibility requiring retransplantation, two arterial
      complications, and two biliary leakages. Our outcomes of emergency
      transplantation were similar to those reported by both the European and Spanish
      Liver Transplantation Registries, despite the small number of patients.

PMID- 23146477
TI  - Impact of blood amylase peak over vascular graft thrombosis in pancreas
      transplantation.
AB  - BACKGROUND: Vascular graft thrombosis (VGT) is still the achuilles heel in
      pancreas transplantation (PT); it is the main cause of nonimmunologic graft loss.
      Early diagnosis is essential to avoid transplantectomy. The aim of our study was
      to analyze the peak amylase during the first 3 days after PT as risk factor for
      VGT. METHODS: This retrospective study included 58 pancreas transplants in 55
      patients from January 2007 to November 2011. They underwent an anticoagulation
      protocol based on unfractionated heparin and low-molecular-weight heparin. The
      technique consisted of enteric drainage and systemic venous drainage. The primary
      endpoint was VGT with consideration of multiple relevant variables. The maximum
      amylase level was determined during the first 3 days after transplantation. A
      receiver operating characteristic analysis was performed to establish a cutoff
      point as (mean plus one standard deviation; 745 mg/dL), calculating the
      sensitivity, specificity, and predictive values. RESULTS: Recipient
      characteristics were 71% males with an overall mean age of 39 years (range, 23
      55) and body mass index 24 (range, 19-36). The donor sex was similar. Mean donor
      age was 32 years with occurrences of hypotension in 9%, cerebrovascular brain
      death in 46%. Mean ischemia time was 10 hours and 45 minutes. Mean blood amylase
      peak was 395 mg/dL. Seven VGT cases were diagnosed during the postoperative
      period including six with complete thrombosis requring transplantectomy.
      Bivariate analysis showed the group of subjects with amylase levels above 745
      mg/dL to display on eight-fold greater risk for VGT (odds ratio = 8.6; P = .032).
      The area under the curve of blood amylase peak during the first 3 days to detect
      VGT was 0.630 (95% confidence interval 0.41-0.84). CONCLUSIONS: A blood amylase
      peak above 745 mg/dL in the first 3 days after transplantation was associated
      with risk for VGT.

PMID- 23146478
TI  - Steroid withdrawal during 5 years following heart transplantation, and the
      relationship between steroid dosage at 1-year follow-up and complications during
      the next 2 years: results from the RESTCO study.
AB  - BACKGROUND: Little information is available regarding the controversial issue of
      steroid withdrawal following heart transplantation (HT), or instead in the
      incidence of adverse steroid effects at dosages typically employed in Spain.
      METHODS: We analyzed the 5-year follow-up records of 1209 patients (82.5% men,
      aged >= 18 years) who underwent HT between 2000 and 2005 and survived at least 1
      month in 13 Spanish centers. The incidences of first steroid withdrawal before 1,
      3, and 5 years post-HT were expressed as Kaplan-Meier probability estimates.
      Three patient groups defined in accordance with steroid dosage at 1-year follow
      up (0, <= 5, and >5 mg/d; groups A, B, and C, respectively) were compared with
      regard to the incidence of de novo hypertension, diabetes, and bone fractures
      over the following 2 years. RESULTS: The 5-year incidence of withdrawal was 28%,
      21% of whom required reintroduction of steroids. Kaplan-Meier probabilities of
      withdrawal before 1, 3, and 5 years post-HT were 8.8% (95% confidence interval
      ([CI] 7.3%-10.7%), 27.8% (CI 25.2%-30.6%), and 30.2% (CI 27.5%-33.2%),
      respectively. At 1-year follow-up, 9.9% of patients were steroid-free, 28.9% were
      taking <= 5 mg/d, and 61.3% >5 mg/d. The 2-year incidence of de novo hypertension
      increased significantly (P = .012) from 13.5% to 29.6% to 35.3% in groups A, B,
      and C respectively. These groups did not differ significantly in regard to the 2
      year incidence of diabetes or bone fractures. CONCLUSIONS: Reintroduction of
      steroids was required by 21% of the 28% of Spanish HT patients who has been
      weaned from steroids within 5 years of HT. The incidence of de novo hypertension
      between 1 and 3 years post-HT increased with steroid dosage at 1-year follow-up.
      De novo diabetes and bone fractures showed no similar significant association.

PMID- 23146479
TI  - Effect of CYP3A5, CYP3A4, and ABCB1 genotypes as determinants of tacrolimus dose
      and clinical outcomes after heart transplantation.
AB  - BACKGROUND: Tacrolimus (Tac) is mainly metabolized by cytochrome P450 3A
      isoenzymes. In a cohort of heart transplant recipients, we investigated the
      effect of CYP3A5, CYP3A4, and ABCB1/MDR1 polymorphisms on Tac dose requirements
      and the risk of developing new-onset diabetes after transplantation (NODAT).
      METHODS: A total of 65 heart transplant recipients were genotyped for 3 single
      nucleotide polymorphisms (SNPs) in the CYP3A5 (SNP rs776746), CYP3A4 (SNP
      rs2740574), and ABCB1 (SNP rs104564). The mean Tac dose values were compared
      between the genotypes. RESULTS: CYP3A5 3 homozygotes (nonexpressers; n = 55, 85%)
      received significantly higher Tac dose compared with CYP3A5 1 carriers
      (expressers). No different NODAT frequencies were found between the genotypes.
      CONCLUSIONS: The CYP3A5 polymorphism was the main determinant of Tac dose
      requirements among heart transplant recipients. This common functional
      polymorphism had no influence on the risk of developing NODAT.

PMID- 23146480
TI  - Accuracy of noninvasive estimation of pulmonary wedge pressure by
      echocardiographic indices in heart transplant recipients.
AB  - BACKGROUND: Pulmonary capillary wedge pressure (PCWP) can be estimated from
      transmitral or color M-mode Doppler flow propagation velocities. However, it has
      been recommended to not use these indices in heart transplant recipients. Our aim
      was to compare the accuracy of color M-mode, Doppler, and Doppler tissue imaging
      (DTI)-derived indices to predict PCWP in heart transplant recipients. METHODS: We
      studied 50 consecutive heart transplant recipients scheduled for routine right
      sided heart catheterization and endomyocardial biopsy. Their mean age was 49 +/-
      17 years and the mean time after heart transplantation was 29 +/- 41 months. An
      echocardiogram was performed immediately after the invasive procedure. We
      analysed PCWP, transmitral flow velocity variables (peak velocity during early
      filling (E) and deceleration time [DT]), color M-mode Doppler flow propagation
      velocity (Vp), and mitral annulus peak early diastolic velocity (E') from DTI.
      Doppler estimated-PCWP (ePCWP) was calculated as follows: (5.27 * E/Vp) + 4.6.
      RESULTS: Mean ejection fraction was 66 +/- 11%. The mean invasive measured PCWP
      was 11.14 +/- 5.4 mm Hg and the mean noninvasive ePCWP was 11.13 +/- 1.8 mm Hg (r
      = 0.66; P < .0001). A good correlation was present between invasive PCWP and
      mitral PW-Doppler and DTI parameters: peak E 91 +/- 22 cm/s (r = 0.34; P = .02)
      and DT 143 +/- 26 s (r = -0.436; P = .002), E/E' ratio medial mitral annulus 10
      +/- 4 cm/s (r = 0.353; P = .026) and E/E' ratio lateral mitral annulus 6 +/- 2
      cm/s (r = 0.462; P = .002). E/Vp was the most accurate index for predicting PCWP
      (r = 0.615; P < .0001). CONCLUSIONS: Compared with other indirect Doppler
      indices, E/Vp showed the best correlation to predict PCWP in heart transplant
      recipients. Despite previous recommendations, PCWP can be accurately estimated
      from color M-mode indices, giving useful information and avoiding the risks of
      invasive measurements.

PMID- 23146481
TI  - Long-term outcome of high-urgency heart transplant patients with and without
      temporary ventricular assist device support.
AB  - BACKGROUND: The use of short-term ventricular assist devices (VAD) in patients
      awaiting high-urgency (HU) heart transplantation (HTx) in Spain has steadily
      increased due to longer waiting times and the new heart allocation system. It is
      unknown whether the use of short-term VAD support in patients with cardiogenic
      shock affects HTx outcome. We sought to investigate long-term outcomes of HU
      transplanted patients with VAD compared with HU transplanted patients without
      device support. METHODS: We retrospectively evaluated all HTx patients
      transplanted between 1999 and 2011 in our institution. Patients were categorized
      by urgency: elective HTx, HU-HTx with VAD (status 0), and HU-HTx without VAD
      (status 1). Actuarial survival rates were compared. RESULTS: Of 237 transplanted
      patients, 55 (23%) were HU-HTx, including 16 on VAD support and 39 without VAD.
      Mean time in the HU waiting list was 6.5 +/- 6 days and mean VAD support was 8.4
      +/- 8 days (range, 1 to 31 days). Assist devices used were Levitronix Centrimag
      (6), Abiomed (9), and extracorporeal membrane oxygenation (ECMO) (1). After a
      mean follow-up of 4.6 +/- 4.1 years (range 0 to 13 years), 22 patients had died:
      5 VAD and 17 non-VAD. The 1- and 5-year survival rates were 73% and 61% for the
      VAD and 74% and 62% for the non-VAD group, respectively (P = ns). Kaplan-Meier
      and Cox regression analyses did not show survival differences, HR 1.11 (95% CI
      0.41-3.02), P = 0.84. The presence of renal failure was associated with increased
      mortality risk, HR 1.9 (95% CI 1.1-3.2), P = 0.02. The presence of renal failure
      was associated with increased mortality risk [HR 1.9 (95% CI 1.1-3.2), P = .02.).
      CONCLUSIONS: In our experience, the long-term outcome of patients receiving HU
      HTx under short-term VAD support is comparable to that of patients undergoing HU
      HTx without VAD support. Patients with renal failure had an increased risk for
      overall mortality in this set of patients.

PMID- 23146482
TI  - Indoleamine, 2-3 dioxygenase activity could be an early marker of graft rejection
      in heart transplantation.
AB  - BACKGROUND: The indoleamine, 2-3 dioxygenase (IDO) is an inducible intracellular
      enzyme with immunosuppressive effects mainly on lymphocyte populations. It has
      been postulated that indirect determination of IDO serum activity may be a marker
      of renal graft rejection, but its potential usefulness in heart transplantation
      (HT) is unknown. METHODS: This longitudinal study included 98 HT patients (83%
      males) who survived >=1 year. Mean age was 54.14 +/- 11.57 years. Serum IDO
      activity was analyzed one month after HT by means of high performance liquid
      chromatography and correlated with the cumulative incidence of acute rejection
      (AR) during one-year follow-up. AR was defined as biopsy-proven >= ISHLT grade 2R
      rejection or empirically treated non-biopsy-proven rejection. The study sample
      was divided into two groups: AR group (n = 51), including patients who
      experienced at least one AR episode during the first year after HT; No-AR group
      (N = 47), including the remaining patients. RESULTS: Mean serum IDO activity one
      month after HT was significantly higher (P = .021) in the AR group (3.32 +/-
      1.56) than in the no-AR group (2.62 +/- 1.35). No significant association between
      serum IDO activity and gender (male: 3.1 +/- 1.56, women: 2.43 +/- 0.99, P =
      .092), recipient age (r = -.07, P = .943) or donor age (r = 0.108, P = 0.293) was
      observed. By means of binary logistic regression, an odds ratio of 1.4 [CI 95%:
      1.033-1.876, P = .03] per unit increase of act-IDO was estimated, with no
      significant modification upon forced adjustment for age and sex. Mean glomerular
      filtration rate 1 month after HT was 67.01 +/- 28.51 mL/min/m(2). No significant
      correlation between this parameter and serum IDO activity was observed (r = .160,
      P = .117). CONCLUSIONS: Our study suggests that serum IDO activity one month
      after HT might be associated with a higher risk of AR during one-year follow-up.
      This association seems to be independent of recipient gender, age or renal
      function.

PMID- 23146483
TI  - Evaluation of lymphoproliferative responses by carboxy fluorescein succinimidyl
      ester assay in heart recipients with infections.
AB  - The analysis of proliferative responses using 5,6-carboxyfluorescein diacetate
      succinimidyl ester (CFSE) in flow cytometry is widely used to assess lymphocyte
      function. The aim of this study was to evaluate nonspecific and specific
      lymphoproliferative responses using CFSE in heart recipients before and after
      transplantation and their association with the development of infection. We used
      four-color flow cytometry to measure the response of peripheral CD3+, CD4+, and
      CD8+ T cells to phytohemagglutinin mitogen (PHA), tetanus toxoid, hepatitis B,
      and influenza vaccines using a CFSE proliferation assay in 12 heart recipients
      and 8 healthy control subjects. Recipients were prospectively evaluated.
      Immunological studies were performed before and at 3 months after
      transplantation. A 12-month clinical follow-up examination sought to detect the
      prevalence of severe infectious complications. Heart recipients (infected [n = 7]
      and uninfected [n = 5]) disclosed significantly lower percentages of
      proliferative responses than healthy controls against PHA at both study points.
      Baseline CD3+, CD4+, and CD8+, antitetanus proliferative responses were
      significantly lower in infected heart recipients than controls. Patients who
      developed infections displayed significantly lower percentages of CD3+CFSE and
      CD8+CFSE cells to PHA mitogen at 3 months after transplantation versus those
      without infections. In conclusion, nonspecific T-cell reactivity to PHA was lower
      in heart recipients with posttransplantation infections.

PMID- 23146484
TI  - Correlation of immunological markers with graft vasculopathy development in heart
      transplantation.
AB  - This study examined the imbalance between T effector cells (Th1 defined as CD3+
      interferongamma+) and T regulatory cells (Treg defined as CD4+CD25(high)FoxP3+)
      as a valuable albeit limited marker of cardiac allograft vasculopathy (CAV) after
      heart transplantation (HTx). CAV remains, with neoplasms, the most important
      cause of death in patients surviving the first year after HTx. It is an immune
      mediated pathology, although nonimmune factors may also play a role. The process
      included concentric fibrous intima hyperplasia that narrows the entire length of
      the affected arteries. Coronary angiography is the usual method of diagnosis.
      Because a transplanted heart is a denervated organ, CAV is not diagnosed until
      the disease reaches an advanced stage, in which case transplantation is the only
      option for treatment. Although the host's immune response against an allogeneic
      graft is the major cause of endothelial dysfunction, the objective of this study
      was to detect anti-allogeneic responses on peripheral blood, seeking to identify
      signs of CAV before classical methods to predict outcomes in HTx recipients. CD3,
      CD4, CD8, CD19, CD56, Th1, and the Treg mononuclear cell populations were studied
      in 37 de novo and 20 long-term (more than 3 years) HTx patients as well as 20
      healthy volunteers using flow cytometry. A progressive increase in CD8 and Th1
      percentages and decrease in the CD4 population were detected during follow-up.
      Although Th1 changes also reflect processes not related to CAV receiver operating
      characteristics analysis of Th1/Treg ratio showed an area under the curve of
      0.976, with an estimated sensitivity of 100% and specificity of 90%. The positive
      prediction value was 58.8% and the negative prediction value, 100%. These results
      prove that the Th1/Treg ratio was an important marker to following host immune
      response after HTx. The results confirm the need to test other T lymphocyte
      subsets.

PMID- 23146485
TI  - Percutaneous coronary interventions and bypass surgery in patients with cardiac
      allograft vasculopathy: a single-center experience.
AB  - INTRODUCTION: Cardiac allograft vasculopathy (CAV) remains a major impediment to
      long-term survival after heart transplantation (HT). Limited data exist regarding
      the impact of coronary revascularization in these patients. OBJECTIVE: To
      evaluate the outcomes of revascularization procedures in patients with CAV
      compared with patients who did not undergo revascularization. METHODS:
      Retrospective analysis of 249 patients who underwent HT at our center between
      June 1998 and December 2009 and who were examined by coronary angiography after
      HT. We included patients with moderate or severe CAV according to the
      International Society for Heart and Lung Transplantation (ISHLT) nomenclature to
      evaluated outcomes after revascularization or diagnostic angiography. Major
      adverse cardiovascular events (MACE) comprised death, acute coronary syndrome,
      coronary revascularization, admission because of heart failure not due to an
      acute rejection episode, and cardiac retransplantation. RESULTS: Moderate or
      severe CAV was detected in 43 patients. Twelve (27.9%) underwent coronary
      revascularization: eight percutaneous interventions and four bypass surgeries.
      Indications for revascularization were symptomatic ischemia or noninvasive
      evidence of ischemia (n = 6, 14.0%) or high-risk asymptomatic CAV (n = 6; 14.0%),
      namely, lesions located in the left main or proximal anterior descending arteries
      or multivessel disease with left ventricular dysfunction. The remaining 31
      (72.1%), who did not undergo revascularization showed an absence of ischemia
      during exercise echocardiography (n = 11; 25.6%) or diffuse disease not amenable
      to revascularization (n = 20; 46.5%). During a mean follow-up of 3.0 +/- 2.4
      years, MACE occurred in three revascularized patients (25.0%), in one with
      absence of stress-induced ischemia (9.1%) and in 13 with nonrevascularizable
      disease (65%; P = .012). CONCLUSIONS: Revascularization procedures were effective
      in HT patients with evidence of ischemia or high-risk CAV. Patients with absence
      of stress-induced ischemia have a good prognosis without revascularization. On
      the other hand, diffuse nonrevascularizable CAV is associated with a poor
      prognosis.

PMID- 23146486
TI  - Cumulative incidence of cytomegalovirus infection and disease after heart
      transplantation in the last decade: effect of preemptive therapy.
AB  - INTRODUCTION: Infection by cytomegalovirus (CMV) is a major concern in solid
      organ transplant (SOT). It increases morbidity and mortality. The prevalence of
      CMV asymptomatic infection and disease is variable among centers, partially
      related to immunosuppressive protocols and therapeutic strategies to treat CMV.
      Induction therapy with basiliximab is associated with fewer CMV infections than
      therapy with OKT3. In our center, universal prophylaxis is used in the first
      month post-heart transplant (HT) and preemptive therapy (PET) is used later,
      according to viral load monitoring. OBJECTIVE: To analyze the short- and long
      term incidence of CMV infection and disease post-HT according to CMV status of
      recipient (R)/donor (D) in a cohort of patients who received induction therapy
      with basiliximab. MATERIALS AND METHODS: Retrospective analysis of 201
      consecutive patients over 18 years of age who underwent HT between February 2001
      (when induction therapy with basiliximab was initiated) and June 2011. Patients
      were divided in two risk subgroups of developing CMV disease: high-risk (D+/R- or
      D-/R- who received blood transfusions or R-, or donor with unknown serostatus)
      and low-risk (any other combination). RESULTS: Of 201 patients (mean age 53.81 +/
      11.61 years, 81.1% men). 165 patients were classified in the low-risk and 36 in
      the high-risk group. The cumulative incidence of asymptomatic CMV infection
      during the first year post-HT was 47%: 46% in the low-risk and 50% in the high
      risk group (P = .668). The incidence of CMV disease during the first year post-HT
      was 7.5%: 3.6% in the low-risk versus 25% in the high-risk group (P < .001).
      CONCLUSIONS: In our series, asymptomatic CMV infection after HT is frequent,
      affecting almost 50% of patients. However, the incidence of CMV disease is very
      low (7.5%), which confirms the effectiveness of PET. The higher incidence of
      disease in the high-risk group recommends closer monitoring of viral load in
      these patients or performing more prolonged universal prophylaxis.

PMID- 23146487
TI  - Postoperative complications in the intensive care unit following lung
      transplantation in adults: results in University Hospital Reina Sofia.
AB  - The postoperative period following lung transplantation remains critical because
      of several complications. Infection, primary graft failure, acute rejection, and
      surgical complications are risk factors for mortality and morbidity. The
      recognition and early treatment of these complications is important to optimize
      outcomes. This article provides an overview of postoperative complications
      observed in our center during the last year. We were particularly interested in
      the influence of variables, such as inotrope usage and Acute Physiology and
      Chronic Health Evaluation (APACHE II) score, a well-known, and validated
      mortality prediction model for general intensive care unit (ICU) patients only
      infrequently reported in the transplantation literature. High APACHE II scores
      were significantly associated with prolonged mechanical ventilation (P = 0.041)
      and a tracheostomy requirement (P = .035). The factors significantly associated
      with an early postoperative death were older donor age (P = .005), prolonged
      donor ICU period (P = .004), need for cardiopulmonary bypass (CB; P = .005), and
      high inotrope requirements in the ICU (P = .034). CB data were biased because we
      selected the worst case patients. Donor age and high inotrope requirements in the
      ICU have been reported previously to be prognostic factors for poor graft
      function. We believe that control of these variables may improve outcomes.

PMID- 23146488
TI  - Prospective study of biomarkers of immune response in lung transplant recipients.
AB  - INTRODUCTION: Studies on biomarkers of tolerance in organ transplantation have
      been widely performed during the last decade. AIM: To assess biomarkers in
      relation to evolution of the immune response among lung transplant recipients.
      METHODS: This multicenter study included 27 lung transplant recipients followed
      before as well as at 7, 14, 30, 60, 90, and 180 days posttransplantation.
      Biomarkers of the immune response based on flow cytometry technology were
      validated in each center. They included intracellular cytokine expression,
      regulatory T-cell level, as well as lymphocyte surface antigen and CD28
      expressions. RESULTS: The 13 patients who developed acute rejection episodes
      showed increased numbers of regulatory T cells at 12 months posttransplant.
      Sixteen patients experiencing infections displayed decreased expression of CD69
      on CD8 T cells within the first year of follow-up. CONCLUSION: High Treg levels
      in the peripheral blood of lung transplant recipients were associated with an
      increased risk of rejection but not infection. Inversely, we observed low levels
      of activated CD8 T cells in infected patients.

PMID- 23146489
TI  - Analytical validation of a homogeneous immunoassay for determination of
      mycophenolic acid in human plasma.
AB  - Mycophenolic acid (MPA) is an immunosuppression agent for the prophylaxis of
      organ rejection in patients receiving allogeneic transplants. The drug is
      administered based in 2 formulations, mycophenolate mofetil (MMF) and enteric
      coated mycophenolate sodium (EC-MPS). MPA acts by specific, reversible,
      uncompetitive inhibition of inosine monophosphate dehydrogenase (IMPDH) and thus
      blocks the proliferation of both T- and B-activated lymphocytes. Therapeutic drug
      monitoring (TDM) constitutes an important part of immunosuppressive treatment
      because of the demonstrated significant intraindividual and interindividual
      variability of its pharmacokinetic behavior. TDM is required to optimize
      immunosuppressive efficacy. We present the analytical validation of a homogeneous
      particle-enhanced turbidimetric inhibition immunoassay (PETINIA) technique for
      determination of MPA in human plasma, and compare with a homogeneous enzyme
      immunoassay technique (EMIT; reference method), both methods adapted on a
      Dimension analyzer (Siemens). We examined 50 human plasma samples from kidney
      transplant recipients treated with MMF or EC-MPA, which were analyzed
      simultaneously by both methods. The interassay precision was 5.95% at a
      concentration of 1.0 MUg/mL, 3.47% at 7.5 MUg/mL, and 3.75% at 12.0 MUg/mL. The
      bias of PETINIA-MPA for each of the 3 quality control sample was <3.0%. Least
      squares linear regression yielded an r-value of 0.994 with the following linear
      regression equation: PETINIA = 0.939 * EMIT - 0.063. Bland-Altman comparison
      presented a mean negative difference of -0.312 MUg/mL (standard deviation [SD],
      0.441), namely, -7.6% for PETINIA-MPA. The PETINIA assay for monitoring MPA
      concentrations is an acceptable method for routine clinical use, with interassay
      imprecision (% coefficient of variation) ranging from 5.9% to 3.7% below and
      above the therapeutic concentration range, respectively. In conclusion, MPA-EMIT
      and PETINIA-MPA methods on Dimension analyzer have a good correlation (r =
      0.994), but PETINIA-MPA method demonstrates a negative average difference of 
      7.6% in comparison with EMIT-MPA method.

PMID- 23146490
TI  - Opportunistic pulmonary infections in solid organ transplant recipients.
AB  - BACKGROUND: Opportunistic pulmonary infections (OPI) represent common life
      threatening complications after solid organ transplantation. Our objective was to
      describe pulmonary infections caused by opportunistic pathogens in solid-organ
      transplant patients. METHODS: We analyzed all adult solid organ recipients
      (liver, heart, kidney, and pancreas) between July 2003 and June 2010, reporting
      all episodes of pulmonary opportunistic infection. RESULTS: During the study
      period, 1656 solid organ transplants were performed and 188 opportunistic
      infections were diagnosed in 163 patients (incidence 10%). In 40 cases, the site
      of infection was the lung (21%) with 57.5% occurring between the first and sixth
      month posttransplantation. The most frequently isolated microorganism was
      Aspergillus spp (n = 25, 63%), followed by Pneumocystis jirovecii (n = 6 cs,
      15%). Twenty-five patients with an opportunistic pulmonary infections died during
      the follow-up including, 16 related to the infection (40%). The causative
      organism responsible for the highest mortality was Aspergillus spp (n = 12; 48%).
      Twenty-one patients with an opportunistic nonrespiratory infection died, five of
      them related to it (4%). Opportunistic pulmonary infection was associated with an
      increased mortality rate (P < .001). There was a trend toward a higher mortality
      among patients who developed OPI during the first 6 months after transplantation.
      CONCLUSIONS: Opportunistic pulmonary infections after solid organ transplantation
      are not infrequent. The period of risk for developing this infectious
      complications goes beyond the first 6 months posttransplantation. Mortality due
      to these infections was high in comparison to that of opportunistic
      nonrespiratory infections. It is important to keep a high index of suspicion for
      infectious complications during all posttransplant periods, as this is the first
      step toward a rapid diagnosis and adequate treatment.

PMID- 23146491
TI  - Study of B-cell subpopulations in lung transplant recipients with posttransplant
      infection.
AB  - BACKGROUND: Posttransplant infection after lung transplantation is a common
      feature due to the immunodeficiency induced by the immunosuppressive load. AIM:
      To assess B-cell subsets in lung transplant recipients suffering at least one
      episode of infection within the first year posttransplantation. METHODS: Twenty
      eight lung transplant recipients were enrolled in the study. Their overall mean
      age was 56.6 +/- 10.7 years and 10 were women (35.7%). All recipients were
      treated with steroids, tacrolimus, and mycophenolate mofetil. B-cell subset
      levels were measured in peripheral blood before as well as 7, 14, 30, 60, 90, and
      180 days posttransplantation. RESULTS: No difference in the absolute number of B
      cell subsets was observed within the first year of follow-up. However, pre
      germinal center-activated naive B cells (Bm2'), defined as IgD(+)CD38(++), were
      increased among patients displaying infections within the first year. The
      increased Bm2' subset was accompanied by a decrease in the double negative (CD27(
      )IgD(-)) B-cell population. CONCLUSION: Infections in lung transplant recipients
      were associated with an increase in the Bm2' subset even before transplantation.
      It is possible that Bm2' cells have a role in response to infection in lung
      transplantation.

PMID- 23146492
TI  - Influence of steroid dosage, withdrawal, and reinstatement on survival after
      heart transplantation: results from the RESTCO study.
AB  - BACKGROUND: Little information is available regarding the consequences of steroid
      withdrawal following heart transplantation (HT) in Spain. METHODS: We analyzed
      the records of 1068 patients (81.6% men) who underwent HT between 2000 and 2005
      in 13 Spanish centers who were aged >= 18 years and who survived at least 1 year.
      Death rates and Kaplan-Meier survival curves for 1 to 5 years post-HT were
      compared among four groups: groups A and B, patients on steroids throughout the
      first 5 years post-HT at dosages of <= 5 mg/d between 1-year and 5-year follow-up
      (group A; n = 148), or >5 mg/d for some part of this period (group B; n = 578).
      Groups C and D were patients from whom steroids were at some point withdrawn
      including group D (n = 73) with and group C (n = 269) without subsequent
      reintroduction into the maintenance regimen. RESULTS: Steroids were withdrawn at
      1.6 +/- 0.9 years post-HT in group C, and 1.7 +/- 1.2 years post-HT in group D.
      The death rate between 1- and 5-year follow-up (deaths per 1000 person-years) was
      44.3% (95% confidence interval 26.2-62.5) in group A, 42.6% (33.7-51.4) in group
      B, 30.5% (19.6-41.4) in group C, and 47.8% (21.8-73.7) in group D. There was no
      significant difference among them or among Kaplan-Meier survival curves of the
      four groups (P = .34 in both cases). Comparison of combined groups C + D with
      groups A + B showed no evidence of a greater mortality among combined groups C +
      D. CONCLUSIONS: The late withdrawal of steroids following HT was not associated
      with increased mortality.

PMID- 23146493
TI  - Risk factors, clinical characteristics, and outcomes of invasive fungal
      infections in solid organ transplant recipients.
AB  - BACKGROUND: Invasive fungal infection (IFI) is an important cause of morbidity
      and mortality among solid organ transplant (SOT) recipients. We sought to assess
      risk factors, clinical characteristics, and current outcomes of IFI in SOT
      recipients. METHODS: We reviewed all episodes of IFI occurring among SOT
      recipients in a university hospital from 2008 to 2011. To determine risk factors
      for IFI we carried out a matched case-control study (1:2 ratio). Control subjects
      were matched for transplant type and timing. RESULTS: We documented 20 episodes
      of IFI among 744 SOT recipients (2.7%). Sixty-five percent of cases were proven
      IFI and 35% were probable IFI. The types of IFI documented were aspergillosis in
      8 cases, candidiasis in 7, pneumocystosis in 3, Emmonsia species in infection 1,
      and disseminated cryptococcosis in 1. Ninety-nine percent of the patients had
      received a prior antibiotic therapy (3 months), 40% presented allograft rejection
      (3 months), and 40% had prior kidney injury. Complications of IFI included septic
      shock (50%), respiratory failure (55%), multiple-organ dysfunction (55%), and
      intensive care unit (ICU) admission (50%). Median days from transplantation to
      diagnosis was 103 for candidiasis (range, 27-4644) and 1195 for aspergillosis
      (range, 0-4319). In a comparison of case patients with 40 matched control
      subjects, case patients more frequently presented prior ICU stay (3 months; P =
      .05), hemodialysis requirement (P = .02), receipt of high-dose prednisone (6
      months; P = .006), and prior antibiotic therapy (P < .001). Prior use of
      antibiotic treatment was the only risk factor for IFI (odds ratio [OR] 93; 95%
      confidence interval [CI], 8.3-1042). Case-fatality rate was 60%. CONCLUSIONS: In
      our recent experience, 2.7% of SOT recipients developed IFI, mainly aspergillosis
      followed by candidiasis. Prior ICU admission, hemodialysis, receipt of high-dose
      prednisone, and prior antibiotic use were more frequent in cases when compared
      with control subjects, with the latter factor being the only independent risk
      factor for developing IFI. Case-fatality rate was high (60%).

PMID- 23146494
TI  - Clinical features and outcomes of tuberculosis in solid organ transplant
      recipients.
AB  - BACKGROUND: Tuberculosis (TB) remains a significant opportunistic infection in
      solid organ transplant (SOT) recipients. Moreover, its optimal treatment in SOT
      recipients is challenging due to the toxicity and potential drug-drug
      interactions of antituberculus drugs. We sought to assess the frequency, clinical
      characteristics, treatments, and outcomes of TB among SOT recipients. METHODS: We
      reviewed retrospectively the medical charts of all TB cases occurring among SOT
      recipients from January 2000 to December 2011, retrieving data regarding baseline
      and clinical features, as well as treatment and outcomes. RESULTS: Eighteen of
      2005 SOT recipients developed TB (0.9%). The frequency according to the type of
      allograft was 0.9% (10 of 1120) for kidney, 1% (7 of 701) for liver, and 0.5% (1
      of 184) for heart recipients. Six patients (33%) had prior exposure to TB: a
      positive tuberculin test (n = 3), a positive quantiferon-TB (n = 1) for a prior
      history of TB (n = 3). None of them received antituberculus prophylaxis. The mean
      time after transplantation to TB diagnosis was 64 months (range 2-169). Five
      patients (28%) developed TB within the first year posttransplantation. The mean
      duration of symptoms before diagnosis was 30 days (range 1-180). Nine patients
      (50%) displayed pulmonary TB; 7 (39%) had disseminated infections, and 2 (11%)
      had lymph node involvement. None of the Mycobacterium tuberculosis isolates were
      resistant to first-line antituberculus drugs. All patients were given isoniazide.
      Most of them received a 3-drug regimen. Rifampin was prescribed in 11 cases.
      Seven patients (5 liver and 2 kidney recipients) developed hepatotoxicity. One
      patient developed rejection without allograft loss. Mortality during
      antituberculus treatment was 17% (3/18). CONCLUSIONS: In this study, 0.9% of SOT
      recipients developed TB, which frequently presented with extrapulmonary
      involvement, causing considerable mortality. Hepatotoxicity mainly among liver
      transplant recipients was a significant therapeutic drawback.

PMID- 23146495
TI  - Eculizumab treatment of acute antibody-mediated rejection in renal
      transplantation: case reports.
AB  - The occurrence of acute antibody-mediated rejection (AMR), especially in more
      severe cases, continues to be associated with a poor prognosis for implant
      survival. Here, we have reported the results of treatment of two patients who
      developed AMR associated with thrombotic microangiopathy immediately after
      transplantation. We used a single dose of eculizumab at an early stage jointly
      with conventional modalities of steroid boluses, plasmapheresis, intravenous
      immunoglobulin, and rituximab. In both cases, the clinical course was favorable.
      Eculizumab, a monoclonal antibody with a high affinity for complement protein C5,
      prevents generation of the final membrane attack complex, blocking this cascade.
      To date, there are a few reports of the usefulness of eculizumab in AMR.
      Eculizumab can help to stop endothelial damage, especially in severe cases that
      show a risk of progression to cortical necrosis, by providing a therapeutic
      window until the other modalities begin to control the immune response. In our
      experience, the use of eculizumab can be beneficial in the treatment of AMR.

PMID- 23146497
TI  - Attitudes and behavior toward organ donation in Greece.
AB  - INTRODUCTION: During the two last decades remarkable progress has been made among
      transplantations in Greece. However, organ donation remains a controversial
      issue. PURPOSE: To explore and determine factors associated with differences in
      willingness to donate organs among Greeks. METHODS: We administered a survey to
      2263 adults living in the region of Thessaloniki. We studied the incidence of
      registered donors, their awareness on the subject of brain death and organ
      donation, their willingness to donate and factors that influence donation of
      their own and their relatives organs, as well as their feelings about such a
      decision. RESULTS: The respondents knew the significance of brain death and organ
      donation; 3.8% were already registered to be donors. Nearly half of them (48.3%)
      wanted to become a donor and 49.1% would donate organs of their relatives; 55.7%
      were afraid of the procedure of organ removal to and 58.3% would feel guilt about
      gifting the organs of a relative. Women were more prone to become donors (odds
      ratio 1.95) and parents were more likely to be registered as donors (odds ratio
      1.84). About 63.7% of Orthodox Christians wished to become donors. Professional
      and educational levels were not observed to influence attitudes. CONCLUSIONS:
      Despite knowledge and willingness regarding organ donation, only a small
      percentage of Greeks are actually registered to be donors.

PMID- 23146498
TI  - Bispectral Index Scale variations in patients diagnosed with brain death.
AB  - INTRODUCTION: Brain death (BD) is defined as the total irreversible loss of brain
      stem function. According to the Greek legislation, BD diagnosis is based on
      clinical criteria that test brain stem function. Bispectral Index Scale (BIS), a
      parameter derived from a mathematical analysis of the electroengephalogram
      depicts brain activity. The aim of our study was to record BIS alterations in
      brain-dead patients. METHODS: Thirty-five brain dead patients according to the
      clinical criteria were included in this study. All patients were hemodynamically
      stable, normothermic, and normocapnic, free of oxygenation disturbances and
      electrolyte abnormalities. Continuous BIS monitoring (BIS XP, A-2000, Aspect
      Medical Systems, Newton, Mass, USA) was performed in all patients for periods
      ranging from 24 to 36 hours. RESULTS: BIS values were 0 for the majority of the
      study period in all patients. However, in 23 patients the BIS value exceeded 30
      for more than 30 minutes. This increase could not be attributed to any external
      stimulation. CONCLUSION: BIS is a noninvasive, easily interpreted method to
      monitor cerebral activity. According to our results, BIS could be helpful in BD
      confirmation but cannot replace the valid clinical tests, which are consistent
      with Greek legislation for this diagnosis.

PMID- 23146499
TI  - Laparoscopic living donor nephrectomy: is there a difference between using a left
      or a right kidney?
AB  - BACKGROUND: The goal of this study was to review the results of 279 laparoscopic
      living donor nephrectomies (LLDN) regarding outcomes of using the left or the
      right kidney. METHODS: Among 279 patients who underwent LLDN between August 1998
      and April 2009, 260 underwent a left (group L) and 19, a right (group R)
      nephrectomy. The two groups were compared regarding intra- and postoperative
      parameters, including pre- and postoperative renal function, length of surgery,
      conversion to an open approach, delayed graft function, and complications.
      RESULTS: There were no significant differences between the two groups regarding
      preoperative glomerular filtration rate (L = 129.5 +/- 32 mL/min versus group R =
      127.3 +/- 26 mL/min), length of surgery (group L = 228 +/- 58 minutes versus
      group R = 226 +/- 62 minutes group), postoperative donor creatinine (group L =
      1.36 +/- 0.9 mg/dL versus group R = 1.48 +/- 0.8 mg/dL), conversion to open
      (group L = 6.6% versus group R = 5.3%), delayed graft function (group L = 7.2%
      versus group R = 6.3%) and recipient postoperative creatinine at 1 month (group L
      = 1.54 +/- 1.4 mg/dL versus group R = 1.32 +/- 1.1 mg/dL). There were three
      intraoperative donor complications in group L (bleeding in one donor required
      transfusion), and none in group R. Similarly, there was a great albeit not a
      significant difference in the number of major postoperative donor complications
      among group L (n = 16) versus group R (n = 2). The right kidney was chosen
      because of the number of vessels (n = 5), presence of cysts (n = 5), size and
      renal function (n = 6), presence of renal stones (n = 2), and tortuous ureter (n
      = 1). The reasons for conversion to open included bleeding, anatomic issues, and
      presence of adhesions. It should be noted that during the last 3 years there were
      no conversions to open, whereas the only conversion among group R was the first
      case. CONCLUSIONS: Intra- and postoperative parameters were comparable between
      the groups. Considering the limitations of the small sample size of right LLDNs
      in this study, it appears that it is as safe and effective as a left procedure.
      The learning curve is extremely important, as can be seen by the lack of
      conversion in the last 3 years.

PMID- 23146500
TI  - Assessment of nonimmunologic factors in kidney transplant recipients according to
      Kidney Disease Improving Global Outcomes.
AB  - INTRODUCTION: Cardiovascular disease is the primary cause of death among kidney
      transplant recipients (KTRs), whereas chronic allograft nephropathy (CAN) is the
      main reason leading to end-stage chronic kidney disease. The etiologies of both
      entities include immunologic and nonimmunologic factors. The management of
      modifiable nonimmunologic parameters has recently been identified by the Kidney
      Disease Improving Global Outcomes (KDIGO) guidelines. The aim of our study was to
      assess the implementation of these guidelines in the outpatient kidney
      transplantation clinic of our hospital. PATIENT AND METHODS: We retrospectively
      monitored the records of 48 transplanted KTRs including 32 males of overall mean
      age 45.1 +/- 10.7 years regarding control of anemia, dyslipidemia, mineral bone
      disorder (MBD), and blood pressure (BP) levels. Data were recorded every 6 months
      for 2 years, starting 1 year after renal transplantation. RESULTS: The estimated
      glomerular filtration rate of patients at baseline was 60.3 +/- 18.8 mL/min/1.73
      m(2) with no significant change during 2 years of follow-up. The control of
      anemia was satisfactory in 42 patients (88%) with hemoglobin values >= 11 g/dL
      during the follow-up. Regarding dyslipidemia management, the aggregate of
      patients showed fasting triglycerides <=500 mg/dL in all measurements. The
      percentage of KTRs with LDL <=100 mg/dL tended to improve from baseline versus
      the end of the study period (20.8% vs 41.7%). Serum calcium was satisfactorily
      controlled in 77% of patients, serum phosphorus in all patients, whereas
      parathyroid hormone (PTH) was abnormal in 60% of KTRs with chronic kidney disease
      stages 3-5. Finally, the BP goal of <130/80 mm Hg was achieved in approximately
      half of the patients. CONCLUSION: Control of nonimmunologic factors was
      satisfactory in terms of renal anemia and MBD, whereas dyslipidemia and BP levels
      were inadequately controlled. There is a clear need for better integration into
      clinical practice of KDIGO guidelines with regard to modifiable nonimmunologic
      factors.

PMID- 23146501
TI  - Simultaneous pancreas-kidney transplantation: initial results from a center in
      Greece.
AB  - AIM: The outcome of simultaneous pancreas-kidney transplantation (SPK) in type 1
      diabetes has dramatically improved in recent years. We report the initial results
      of our SPK program. PATIENTS AND METHODS: From 2008 to 2010, we performed and
      prospectively obtained data on 4 SPKs in 4 type 1 diabetic patients with chronic
      renal failure. The recipients were 3 men and 1 woman, of overall mean age of
      40.75 +/- 4.78 years, mean time from diabetes diagnosis of 27 +/- 15 years, and
      time on dialysis of 3.5 +/- 0.57 years. All grafts were procured from multiorgan
      brain-dead donors of mean age 26 +/- 8.16 years and mean body weight of 74 +/-
      4.34 kg. The pancreatic grafts were transplanted first into the right iliac fossa
      with mean cold ischemia times of 10.62 +/- 3.09 hours for the pancreatic and
      14.00 +/- 2.97 hours for the renal grafts. Pancreas arterial inflow was re
      established by an end-to-side anastomosis of an extension Y-graft to the
      recipient right iliac artery. The portal vein was sutured to the iliac vein
      directly. The exocrine secretions of the pancreas were managed by
      duodenojejunostomy extraperitoneally (n = 3) or intraperitoneally (n = 1). The
      ureteral anastomosis was performed using the Taguchi technique. RESULTS: After
      SPK, endocrine pancreatic function was immediately restored in all patients.
      Insulin administration was stopped within the first 24 hours after surgery. Two
      patients displayed delayed renal graft function necessitating dialysis for 9 and
      23 days, respectively. The postoperative course was prolonged with a mean
      hospital stay of 82 +/- 1 day. At a 31.75 +/- 9.03 months follow up all patients
      are alive with functioning grafts. CONCLUSION: Our experience with SPK, although
      limited, has shown encouraging results over a short follow-up period.

PMID- 23146502
TI  - Prevalence and clinical impact of cytomegalovirus infection and disease in renal
      transplantation: ten years of experience in a single center.
AB  - INTRODUCTION: Renal transplantation is regarded as the optimal treatment for
      patients with end-stage renal disease. Despite significant improvements in
      surgical techniques and immunosuppressive therapy, long-term graft survival has
      not markedly increased over the years, due in part to the occurrence of
      cytomegalovirus (CMV) infection. PATIENTS AND METHODS: Between January 2001 and
      September 2011, we performed 592 kidney transplantations (214 living and 378
      cadaveric donors). All patients received induction therapy with interleukin (IL)
      2 monoclonal antibodies or antithymoglobulin (ATG) combined with calcineurin
      inhibitors, mycophenolate mofetil, or mTOR antagonists and steroids. All CMV
      seronegative patients and all subjects receiving ATG induction were prescribed
      prophylactic therapy with ganciclovir-intravenous (IV) for 15 days 2.5 mg/kg BW
      bid and thereafter oral valgancyclovir once a day. CMV infection was diagnosed
      using a CMV-PVR of >= 600 copies. We analyzed the time to manifestations of CMV
      infection, or positive CMV-PCR, patient and graft survival, serum creatinine
      (Cr), and blood urea nitrogen (BUN) values before and after CMV infection, as
      well as type of immunosuppression therapy. RESULTS: The overall incidences of CMV
      infection and CMV disease were 76/592 (12.8%) and 23/592 (3.9%), respectively.
      The mean +/- standard deviation (SD) times to positive CMV-PCR and CMV disease
      were 16.66 +/- 23.38 months and 106 +/- 61.2 (range, 28-215) days, respectively.
      Mortality was 1% (6/592) among our whole population, 7.9% (6/76) for CMV
      infected, and 26% (6/23) in the CMV disease cohort. Cr and BUN showed no
      significant differences among the groups. CONCLUSIONS: CMV infection and CMV
      disease comprise significant clinical problems, increasing morbidity and
      mortality. The use of prophylactic anti-CMV treatment is of paramount importance.

PMID- 23146503
TI  - Course and outcome of renal transplant recipients admitted to the intensive care
      unit: a 20-year study.
AB  - BACKGROUND: Renal transplantation represents the main treatment for end-stage
      renal disease. The goal of this study was to evaluate the course and outcome of
      renal transplant recipients admitted to the intensive care unit (ICU) and to
      analyze factors determining prognosis and mortality. METHODS: The demographic
      features, data admission characteristics, and ICU courses of all renal transplant
      recipients admitted to our ICU from 1992 to 2012 were evaluated to analyze
      factors for mortality. RESULTS: Eleven women and 50 men of mean age 45.5 +/- 12.5
      years were included in the study. Acute Physiology And Chronic Health Evaluation
      (APACHE II) and Sequential Organ Failure Assessment (SOFA) scores on ICU
      admission were 20 +/- 5.7 and 8.5 +/- 3.5, respectively. The main reasons for
      admission were as follows: sepsis (n = 27) or immediate postoperative
      complications (n = 16). Thirty-five patients during their ICU stay required
      hemodialysis and 34 needed catecholamines. The mortality rate was 42.6%. APACHE
      II Score, dialysis requirement, and sepsis as a reason for ICU admission were
      independently related to the mortality. CONCLUSIONS: The mortality rate was
      higher than that of the general ICU population (42.6% vs 30%). The main reason
      for ICU admission of renal transplant recipients was sepsis.

PMID- 23146504
TI  - Infections related to renal transplantation requiring intensive care admission: a
      20-year study.
AB  - INTRODUCTION: The aim of this study was to evaluate infection complications as
      the reason for intensive care unit (ICU) admission among transplant recipients.
      METHODS: We studied all renal transplant recipients with infectious complications
      admitted to our ICU from 1992 to 2012:44.3% of all renal transplant recipients
      admitted to ICU. The epidemiology and prognosis of infectious complications
      requiring ICU admission were evaluated with analysis of mortality factors.
      RESULTS: The 22 men and 5 women included in this study showed a mean age of 42.7
      +/- 12.3 years. The Acute Physiologic and Chronic Health Evaluation II and
      Seguential Organ Failure Assessment scores on ICU admission were 20 +/- 4.6 and
      8.6 +/- 3.9, respectively. The main infections complications requiring ICU
      admission were cytomegalovirus pneumonia (n = 15) and aspergillus pneumonia (n =
      4). Sixteen patients required hemodialysis and 14, catecholamine support upon ICU
      admission owing to septic shock. The mortality rate among study patients was
      62.9%, versus 26.5% for noninfectious renal transplant recipients requiring ICU
      admissions. Catecholamine support at ICU admission was independently related to
      mortality. CONCLUSION: The mortality rate of renal transplant recipients admitted
      to ICU owing infection complications was higher than that of noninfected renal
      transplant patients. These data suggest that infections and septic shock in renal
      transplant recipients requiring ICU admission worsen their outcome significantly.

PMID- 23146505
TI  - The effect of hyponatremia on the outcome of patients after orthotopic liver
      transplantation.
AB  - Predicting the prognosis of cirrhotic patients is considered to achieve a fair
      allocation among patients awaiting orthotopic liver transplantation (OLT). Serum
      sodium (Na) concentrations are associated with reduced survival among patients
      with cirrhosis. The mortality risk of cirrhotic patients, as defined by the Model
      for End-Stage Liver Disease (MELD) score, is considered to be higher in
      hyponatremic patients. The aim of this study was to record complications and
      outcomes of severely hyponatremic patients after OLT. We retrospectively studied
      75 recipients of OLT over the last 3 years. Hyponatremic patients showed lower 30
      day and intensive care unit (ICU) survivals (P = .022 and .028, respectively),
      higher rates of neurological complications (P = .038), renal failure (P = .001),
      and prolonged duration of mechanical ventilation (P = .000) and ICU stay (P =
      .000). Severe hyponatremia was related to a greater risk for neurological and
      renal complications after OLT.

PMID- 23146506
TI  - Acute kidney injury after orthotopic liver transplantation.
AB  - Acute kidney injury (AKI), one of the most frequent complications in the early
      period after liver transplantation, causes serious obstacles in the management of
      these patients affecting their outcomes. We studied retrospectively 79 subjects
      who underwent orthotopic liver transplantation (OLT). AKI was defined as an
      elevation of serum creatinine 1.5 times above baseline or an absolute serum
      creatinine level > 2 mg/dL. Our aim was to analyze the incidence, correlation
      with prior renal impairment, outcomes of AKI after OLT. Twenty-two patients
      (29.3%) developed AKI after OLT with 31.81% of the requiring renal replacement
      therapy. Among patients with AKI the duration of mechanical ventilation was
      prolonged (P = .001), length of stay in the intensive care unit was greater (P =
      .001), infections were more common (P = .016), and 30-day and 1-year mortality
      rates higher (P = .018). Logistic regression analysis showed post-OLT AKI to be
      an independent risk factor for 1-year mortality after OLT.

PMID- 23146507
TI  - Liver transplantation for hepatocellular carcinoma using extended criteria donor
      grafts.
AB  - BACKGROUND: Liver transplantation (OLT) represents the treatment of choice for
      small hepatocellular carcinomas (HCC) in patients with end-stage liver disease.
      However, because of organ scarcity, alternative options must be explored, such as
      the use of extended criteria donor (ECD) grafts. PATIENTS AND METHODS: We
      reviewed data of transplanted HCC patients using ECD grafts. Statistical analysis
      included uni- and multivariate Cox proportional hazards regression and survival
      analysis using the Kaplan-Meier method with the log-rank test. RESULTS: Over a 6
      year period, we transplanted 53 HCC patients with ECD grafts. The 38 men and 15
      women showed a mean age of 56.3 +/- 8.26 years. Thirty-four patients underwent a
      bridging treatment before OLT. Thirty-eight patients (72%) were outside the Milan
      criteria. The median value for alpha fetoprotein (AFP) level was 30.7 ng/dL.
      Pathologic tumor grade was G1 (n = 4), G2 (n = 32), G3 (n = 6), or Gx (n = 11).
      Median follow-up time was 23 months (range, 9-75). Overall 3- and 5- year patient
      survivals were 79% and 74%, respectively. The 5-year survivals for patients
      within or outside the Milan criteria were 87% versus 69%, respectively (P =
      .3728). Donor transaminases and post-OLT hemodialysis were prognostic factors for
      patient survival upon mutivariate regression analysis (P = .0043 and P = .0003,
      respectively). CONCLUSION: OLT with ECD grafts constitutes an additional option
      for patients with HCC and cirrhosis, particularly subjects outside the Milan
      criteria. The risk- benefit ratio in these instances should be evaluated on a
      case-by-case basis.

PMID- 23146508
TI  - Orthotopic liver transplantation in patients with portal vein thrombosis in the
      absence of hepatocellular carcinoma.
AB  - BACKGROUND: Liver transplantation (OLT) in the setting of portal vein thrombosis
      (PVT) has been a matter of controversy in the past. We herein report our
      experience with OLT for PVT in the absence of hepatocellular carcinoma. PATIENTS
      AND METHODS: Data from patients undergoing OLT for end-stage liver disease,
      having a documented PVT before OLT, were reviewed. RESULTS: Twenty-five patients
      were included for the period July, 2003 to December, 2009. There were 20 men and
      5 women of median age 57 years. Median values for waiting time and Model for End
      Stage Liver Disease score were 150 days and 18, respectively. PVT was classified
      as grade II (n = 6), IIIa (n = 7), IIIb (n = 9), or IVa (n = 3). Partial portal
      vein resection/reconstruction, operative thrombectomy, and eversion
      thromboendovenectomy were performed in 2, 16, and 7 instances, respectively.
      After a median follow-up of 18 months, 14 patients are alive. Survival rates at
      3, 6, 9, and 12, months and 3 years post-OLT were 68%, 64%, 61%, 61%, and 61%,
      respectively. PVT grade was a negative predictor of survival by Cox proportional
      hazard analysis (P = .0253). CONCLUSION: Despite the technical innovations in
      recent years, PVT grade correlated with poor patient survival irrespective of the
      surgical technique.

PMID- 23146509
TI  - Claudin-7 expression in hepatocellular carcinoma.
AB  - BACKGROUND: The importance of adhesion molecules for local invasion by neoplastic
      cells and development of metastasis has been confirmed by numerous studies over
      the past decade. Claudins are integral parts of tight junctions. The aim of the
      present study was to examine the significance of the expression of claudin-7
      messenger RNA (mRNA) as a prognostic factor for hepatocellular carcinoma (HCC).
      PATIENTS AND METHODS: We examined liver tumor and nontumor tissues from 20 HCC
      patients who underwent resection or liver transplantation. RESULTS: A significant
      increase in the expression of claudin-7 was observed in tumor versus nontumor
      tissues. There was no significant correlation between the expression profile of
      claudin-7 mRNA and patient demographic data, the presence of cirrhosis, or the
      histological stage of tumor differentiation or vascular invasion. Survival
      analysis showed a trend toward a better prognosis among patients with
      overexpression of claudin-7 in tumor tissues.

PMID- 23146510
TI  - Hepatic artery thrombosis after orthotopic liver transplantation: 3 patients with
      collateral formation and conservative treatment.
AB  - Hepatic artery thrombosis (HAT), a serious complication after orthotopic liver
      transplantation (OLT), can lead to patient death in the absence of
      revascularization or retransplantation. Herein we have presented clinical
      characteristics, imaging findings, and long-term outcomes of 3 OLT patients with
      HAT who were treated conservatively and developed hepatic arterial collaterals.
      These patients underwent transplantation due to hepatitis B cirrhosis,
      cryptogenic cirrhosis, or hepatitis C infection and alcoholic disease. They
      presented with bile duct stenosis and/or a bile leak at 1, 3, and 36 months after
      transplantation, respectively, and were treated with percutaneous drainage and
      stent placement, endoscopic retrograde cholangio-pancreatography (ERCP), or
      reanastomosis of the bile duct over a T tube. HAT was confirmed using
      multidetector computed tomography (MDCT) 3-dimensional (3D) angiography and
      Doppler sonography. They survive in good condition with normal liver function at
      30, 50, and 42 months after OLT, respectively. Development of collateral arterial
      circulation to the liver graft was detected with MDCT 3D angiography and Doppler
      sonography. From our experience with 3 patients and a literature review, we
      believe that there are a number of patients who experience long-term survival
      after the diagnosis of irreversible HAT and the development of collaterals.
      Although this group is at high risk for sepsis and biliary complications, these
      are usually self-limiting complications due to improved treatment regimens. The
      development of collateral arterial flow may also be beneficial.

PMID- 23146511
TI  - How can we treat a patient with liver cirrhosis (hepatitis C virus),
      hepatocellular carcinoma, and synchronous colon cancer?
AB  - INTRODUCTION: The coexistence of liver cirrhosis with hepatocellular carcinoma
      (HCC) and colon cancer (Ca), which is a rare clinical condition, was treated in a
      liver transplant recipient. PATIENTS AND METHODS: A 46-year-old man, diagnosed
      incidentally during an ultrasound (US) examination with a 3.5-cm HCC in segment
      VII related to chronic hepatitis C virus (HCV), was referred for liver resection.
      He underwent a laparoscopic protocol evaluation for liver cirrhosis. Liver
      appearance and biopsy of the left lobe showed Child B/C liver cirrhosis. Because
      he fulfilled the Milan criteria, we suggested an orthotopic liver transplantation
      (OLT). During protocol colonoscopy, we discovered an ulcerative sigmoid colon Ca.
      Three weeks after completing the pre-OLT assessment he underwent an OLT and was
      discharged home on day 9 on an immunosuppressive regimen of Everolimus, Myfortic,
      and Prezolone. Two months after transplantation, the patient underwent a
      sigmoidectomy and for nearly 1 month thereafter received chemotherapy for colon
      Ca (6 cycles of FOLFOX:Folinic Acid+Fluorouracil+Oxaliplatin). One and a half
      years after OLT, patient was in good condition but presented with an increased
      alpha fetoprotein (a-FP) without other findings. A couple of months later we
      discovered a colon Ca recurrence and 3 small liver metastases. Patient underwent
      a bowel resection with Hartmann's procedure. Almost immediately after the last
      operation, he was found to suffer multiple myeloma. He underwent chemotherapy for
      both malignancies with good responses, but a few months later died of severe
      sepsis. DISCUSSION: The relevant literature regarding treatment of liver
      cirrhosis complicated with HCC and synchronous colon Ca reveals poor and
      controversial outcomes. Our patient underwent chemotherapy immediately after
      colon resection in the presence of with a good functioning liver. Although his
      condition was satisfactory after OLT, the optimal treatment of such complicated
      patients is as yet uncertain.

PMID- 23146512
TI  - Infections after orthotopic liver transplantation in the intensive care unit.
AB  - PURPOSE: The purpose of the study was to assess the characteristics and risk
      factors of infections in the early period after orthopic liver transplantation
      (OLT) among adult patients. MATERIAL AND METHODS: We studied 75 patients who
      underwent OLT over 3 years from 2008 to 2010. We recorded all infections that
      developed during hospitalization in the intensive care unit (ICU) their outcomes,
      and the possible risk factors. RESULTS: During the study period in 80 OLT we
      recorded 19 bloodstream infections (47.5%), 7 ventilator-associated pneumonias
      (VAP; 17.5%), and 14 intra-abdominal infections (35%). Among the 40 isolated
      microbes, 72.5% were Gram negative, 25% were Gram positive, and 2.5% were fungi.
      The median time to developing the infection was 4.95 days (range 2-10). Patients
      with infections showed longer durations of mechanical ventilation, longer lengths
      of ICU stay, and lower 1-year survivals.

PMID- 23146513
TI  - Imaging of complications of liver transplantation: multidetector computed
      tomography findings.
AB  - BACKGROUND: Liver transplantation is the treatment of choice for patients with
      end-stage liver disease; however, it is associated with a multitude of
      postoperative complications. Herein we have presented our experience with the
      application of multidetector computed tomography (MDCT) in the follow-up of liver
      transplant recipients. PATIENTS AND METHODS: Twenty-four liver transplantation
      patients were examined with triphasic hepatic computed tomography. Both
      symptomatic and asymptomatic patients were included in the study. Examinations
      were performed using a multidetector scanner. RESULTS: We documented seven cases
      of thrombosis, three stenosis, and two hepatic artery (HA) aneurysms. Portal vein
      (PV) stenosis and PV thrombosis were observed in two cases each. We observed one
      case of synchronous HA and PV stenosis; one inferior vena cava (IVC) and left
      renal vein thrombosis, and one IVC thrombosis. In three cases of HA obstruction
      we observed transplant neovascularization. One HA obstruction and one HA stenosis
      were accompanied by bilomas. Finally, we discovered three cases of hepatocellular
      carcinoma. CONCLUSION: In our experience MDCT as a single noninvasive
      examination, was a sensitive means to detect and evaluate vascular complications
      after liver transplantation, offering adequate information concerning the liver
      parenchyma, the rest of the abdomen, and to a lesser extent the biliary tract.

PMID- 23146514
TI  - Sorafenib treatment for recurrent hepatocellular carcinoma after liver
      transplantation.
AB  - BACKGROUND: With an increasing number of patients with hepatocellular carcinoma
      (HCC) undergoing liver transplantation (OLT), HCC recurrence remains the main
      limiting factor for long-term survival. We herein report our experience with
      sorafenib treatment for HCC recurrence post-OLT. PATIENTS AND METHODS: We
      reviewed data on transplanted HCC patients receiving sorafenib for HCC
      recurrence. RESULTS: Fourteen patients were included for the period November 2006
      to February 2011. There were 9 men and 5 women of median age of 57 years. Twelve
      patients (86%) received rescue grafts through Eurotransplant allocation. Median
      values for alpha fetoprotein levels, Model for End-Stage Liver Disease score,
      sorafenib daily dose, and length of treatment were 97 ng/mL, 10, 400 mg, and 6.5
      months, respectively. Sorafenib side effects led to discontinuation (n = 4) or
      reduction (n = 2) of the daily dose. Four patients experienced tumor progression
      during treatment. Seven patients are currently alive, 3 patients died of tumor
      progression, and 4 patients of non-tumor-related causes of death. Median survival
      was 25 months. CONCLUSION: Sorafenib treatment for HCC recurrence in transplant
      recipients represents a challenging oncologic approach that requires further
      validation in prospective, multicenter studies.

PMID- 23146515
TI  - Cholecystectomy due to symptomatic gallbladder disease after orthotopic liver
      transplantation: report of three cases.
AB  - Although biliary stones and sludge are relatively common after liver
      transplantation (OLT), symptomatic cholecystolithiasis or acute cholecystitis
      have rarely been reported. Until the early 1990s few transplant centers preserved
      the donor's gallbladder for transplantation with the liver graft. This technique
      allows one to perform procedures, such as cholecystojejunostomy or a donor
      gallbladder conduit for biliary tract reconstruction, to treat posttransplant
      biliary complications. Herein we have reported three cases of successful either
      laparoscopic or open cholecystectomy for symptomatic cholecystolithiasis or acute
      cholecystitis between 14 and 19 years after OLT, as well as a systematic
      literature review.

PMID- 23146516
TI  - Descemet's stripping endothelial automated keratoplasty using Tan EndoGlide
      endothelium insertion system.
AB  - PURPOSE: The purpose of this study was to evaluate early visual and refractive
      outcomes of Descemet's stripping endothelial keratoplasty (DSAEK). METHOD: Nine
      eyes of 7 male and 2 female patients, mean age 73 years, were treated with DSAEK.
      Eight had pseudophakic bullous keratopathy and 1 had advanced Fuch's syndrome.
      Patients were followed up for a mean of 11.4 months (range, 4-26). The DSAEK
      technique consisted of stripping Descemet's membrane and endothelium from a
      recipient cornea and transplanting the posterior stroma and endothelium of a
      donor cornea using the Tan EndoGlide. The mean operating time was 61.89 minutes
      (standard deviation [SD], 9.3). RESULTS: The median donor diameter was 8.375 mm
      (range, 8.25-8.75) and the mean donor thickness was 114.4 MUm (range, 98-129).
      Mean preoperative sphere was -2.41 that changed postoperatively in -1.21. Mean
      endothelial cell loss was 25% (range, 23%-45%) at 6 months after surgery. Corneal
      pachymetry was reduced from 796.6 MUm preoperatively to 535.5 MUm
      postoperatively. Best corrected vicual acuity (BCVA) was 20/40 or better
      postoperatively and exceeded the preoperative BCVA in all eyes. No graft failure
      was present. Two partial graft dislocations (1st and 5th postoperative day) were
      observed. One graft was successfully attached after reinjecting an air bubble
      (rebubbling) in the anterior chamber and the other graft was reattached with 4
      10/0 nylon sutures after failed rebubbling. CONCLUSIONS: The key to successful
      endothelial transplantation is the protection and preservation of as many donor
      endothelial cells as possible. The TAN EndoGlide is a device that consistently
      delivers a donor lenticule through a small incision with minimal endothelial
      loss, while making the insertion procedure relatively reliable and consistent,
      with the surgeon in full control of the donor at all stages of insertion. The
      endothelial cell loss during this technique is comparable (if not better) with
      other endothelial graft insertions systems.

PMID- 23146517
TI  - Preterm delivery in a parturient candidate for emergency liver transplantation
      after hepatitis B virus infection related fulminant liver failure.
AB  - This case shows the development of fulminant hepatic failure due to acute
      hepatitis B virus infection in a multipara (32(nd) week of gestation) candidate
      for an emergency liver transplantation. Preterm labor began and she delivered a
      preterm healthy male baby. Postpartum, there were complications including a
      massive hemorrhage that was managed adequately. We also reviewed the literature
      regarding causes, complications, and management of acute liver failure during
      pregnancy and labor.

PMID- 23146518
TI  - Successful salvage delivery and liver transplantation for fulminant hepatic
      failure in a 34-week pregnant woman: a case report.
AB  - We report the case of a 40-year-old multiparous woman with fulminant hepatic
      failure due to acute hepatitis B virus infection who underwent a successful
      cesarean delivery of a healthy male fetus at 34 weeks, gestation and a few hours
      thereafter successful salvage orthotopic liver transplantation (OLT). There were
      no obstetric complications; the neonatal outcome was excellent. At 27 months,
      follow-up, the patient is doing well, and the newborn exhibits normal
      development. OLT for acute liver failure during pregnancy is an uncommon
      occurrence with variable outcomes. This case illustrates the challenge of
      treating this rare condition and demonstrates that a salvage double surgical
      approach-emergency delivery and OLT-is a feasible therapeutic option for
      treatment of these patients.

PMID- 23146519
TI  - Incarcerated diaphragmatic hernia after right hepatectomy for living donor liver
      transplantation: case report of an extremely rare late donor complication.
AB  - Living donor liver transplantation has evolved to an indispensable surgical
      strategy to minimize the mortality of adult and pediatric patients awaiting
      transplantation. The crucial prerequisite to performing this procedure is a
      minimal risk of donor morbidity and mortality. A 46-year-old woman underwent
      right hepatectomy for living donor liver transplantation. Two and a half years
      after liver donation, she presented with upper abdominal pain and fullness.
      Radiographic evaluation revealed an incarcerated diaphragmatic hernia of the
      right hemithorax. After emergency laparotomy and evaluation of the right
      hemithorax, a partial jejunal resection was performed due to ischemic findings.
      The diaphragmatic hernia was repaired. Diaphragmatic hernia is a rarely reported
      complication of right donor hepatectomy for transplantation and should be
      considered to be a potential late complication.

PMID- 23146521
TI  - Treatment of severe psoriasis with etanercept in a pancreas-kidney transplant
      recipient.
AB  - Severe psoriasis is a rare condition under immunosuppressive therapy. We describe
      a 42-years-old man with psoriasis since the age of 22 years. The patient
      underwent a combined pancreas-kidney transplantation at the age of 32 because of
      Goodpasture syndrome with renal and pulmonary involvments and type 1 diabetes
      mellitus. Seven years later a pancreas retransplantation was performed due to
      nonfunction of the original pancreas allograft. Despite intensive systemic
      immunosuppression, consisting of prednisone, tacrolimus, and mycofenolate
      mofetil, and topical treatment with dithranol and steroids, there was significant
      worsening of psoriasis. In October 2009 we initiated therapy with etanercept (25
      mg s.c.) twice weekly under close clinical and laboratory monitoring. Improvement
      was rapid with a decrease in Psoriasis Area and Severity Index (PASI) from 25.2
      to <5 during the first months of treatment without a severe infection or other
      adverse reaction. Graft functions were not affected by the treatment. The patient
      remains till now on the same regimen and is almost free of skin manifestations.
      To our knowledge so far only 2 cases of etanercept therapy in psoriasis have been
      reported in liver transplant recipients. In both cases the treatment was well
      tolerated and effective. Psoriasis therapy in organ transplant recipients
      represents a major challenge. Biological agents such as etanercept may provide an
      effective option for refractory cases.

PMID- 23146520
TI  - Hepatitis B reactivation in a renal transplant patient due to a surface antigen
      mutant strain: a case report.
AB  - INTRODUCTION: Reactivation of hepatitis B virus (HBV) is a complication of
      immunosuppressive treatment in patients with a history of HBV exposure. CASE
      PRESENTATION: Herein we have reported a case of reactivation after renal
      transplantation in a 52-year-old male chronic HBV carrier who was treated with
      hepatitis B immunoglobulin (HBIg) prophylaxis immediately after transplantation
      in addition to cyclosporine, mycophenolate mofetil and prednisolone for
      maintenance immunosuppression. After application of rituximab, the patient
      developed clinical hepatitis with a high load of HBV DNA. Sequence analysis of
      the surface (S) antigen corresponding to the amino acid residues 101-186
      (including the a-determinant region) revealed a genotype D mutant strain, subtype
      ayw3 with a single amino acid substitution D144E within the S gene. CONCLUSION:
      This case suggested that immunosuppressive treatment enhanced with rituximab
      promoted the emergence of an HBV mutant within the determinant region of the S
      antigen, which escaped HBIg immunoprophylaxis causing HBV reactivation in a
      kidney transplant recipient.

PMID- 23146522
TI  - Ochroconis gallopavum infection in a lung transplant recipient: report of a case.
AB  - Disseminated phaeohyphomycoses are rare infections caused by dematiaceous fungi.
      Ochroconis gallopavum is a neurotropic dematiaceous mold responsible for life
      threatening respiratory and central nervous system infections in domestic poultry
      and in immunologically compromised humans. The world literature describes only 13
      previous O gallopavum infections in solid organ transplant recipients. We report
      herein an O gallopavum phaeohyphomycosis with involvement of skin in a transplant
      recipient. A 69-year-old white man with a history of bilateral lung
      transplantation 6 years ago presented with acute onset of severe respiratory
      distress. Chest X-ray showed no evidence of pneumonia. Lung function showed
      bronchiolitis obliterans syndrome. Excision biopsy was performed because of a
      suspected pigmented basal cell carcinoma. Histopathology revealed dermal
      granulomatous dermatitis, focally suppurative, dominated by epitheloid cells with
      brownish round fungi. Further microbiological work-up of the biopsy specimen
      subsequently revealed O gallopavum as the causative organism. No brain
      involvement was observed. Antimycotic therapy with voriconazole 200 mg twice a
      day was immediately initiated and the patient was treated for 3 months.
      Additional intravenous therapy with tobramycin and imipenem was started upon
      detection of Enterobacter clocae and Enterococci in the sputum. The patient
      recovered during the next few weeks and was discharged on day 26.

PMID- 23146524
TI  - What's new in renal and pancreatic transplantation in 2011?
AB  - At the 11th meeting of the SFT Congress in Montpellier, several presentations
      were devoted to humoral rejection of kidney transplants, new immunosuppressive
      drugs, cancer after transplantation, and second pancreas transplantations. The
      main information drawn from these papers is summarized in this brief review.

PMID- 23146525
TI  - Outcomes of renal transplantation in obese recipients.
AB  - PURPOSE: Although obesity has been shown to paradoxically increase dialysis
      patient survival, its impact has not been clearly defined on renal
      transplantation. We assessed outcomes of obesity renal transplant patients by
      evaluating graft and patient survivals. PATIENTS AND METHODS: A single
      institution, retrospective study was performed on 202 renal transplant recipients
      from January 2004 to December 2008 excluding two combined kidney and liver
      transplantations. Recipients were classified based on body mass index (BMI) at
      the time of transplantation: obese (BMI >= 30 kg/m(2)) and nonobese recipients
      (BMI < 30 kg/m(2)). The comparative analysis included surgical complications,
      hospital stay, onset of delayed graft function (DGF), acute rejection episodes
      and graft patient survivals. RESULTS: Twenty-one renal transplants were performed
      in obese recipients versus 179 in the control group. Obese patients were older
      (53.3 +/- 11.2 versus 46.4 +/- 14.4 years old; P = .035) and more often diabetic
      (29% +/- 0.46 versus 60% +/- 0.24, P = .001), but there were no differences among
      other combidities of high blood pressure, arteriopathy, thrombophilia, and
      smoking. Obesity did not appear to be a risk factor for urinary or vascular as
      well as parietal complications, but did tend to augment lymphatic complications
      (14.3% +/- 0.36 versus 4.5% +/- 0.21; P = .065). DGF occurred more frequently in
      obese patients (38% +/- 0.50 versus 14% +/- 0.34; P = .004) and hospital stays
      were therefore longer in this group (24.9 +/- 23.53 days versus 15.6 +/- 13.67
      days; P = .008). Graft (hazard ratio [HR] 1.22; 95% confidence interval [CI]
      [0.25-6.0], P = .63) and patient survivals (HR:0,81; 95% CI [0.12- 5.3], P = .83)
      were comparable between the groups. CONCLUSION: Obese patients seeking renal
      transplantation are usually older and more often diabetic compared with nonobese
      recipients. The higher rate of lymphatic complications and DGF lead to longer
      hospital stays among the group with BMI >= 30 kg/m(2). However, long-term results
      showed similar graft and patient survivals as nonobese patients. Consequently,
      there seemed to be no reason to avoid renal transplantation in obese recipients.

PMID- 23146526
TI  - Renal function of renal transplantation patients after hospitalization in an
      intensive care unit.
AB  - Kidney transplantation is the favored method to treat end-stage renal disease.
      Some recipients develop severe diseases requiring admission to an intensive care
      unit (ICU). Acute kidney injury (AKI) is a common complication among critically
      ill patients but few data are available among renal transplant recipients. The
      aim of this monocenter retrospective study was to describe renal function in
      kidney transplant recipients admitted to an ICU and to evaluate their renal
      functional recovery after this stay. We identified all renal transplant
      recipients admitted to our medical ICU from January 1, 2001, to December 31,
      2010: namely, 79 stays by 62 patients. We used the glomerular filtration rate
      criteria of the RIFLE classification to evaluate AKI during the ICU stay. During
      the ICU stay, 56 patients (70.9%) were classified as "no AKI" according to the
      RIFLE classification; 11 (13.9%) belonged to class R, 10 (12.7%) to class I, and
      2 (2.5%) to class F. Overall, 24% of the patients needed dialysis during the ICU
      stay. Mortality rate at 3 months after the ICU stay was 25.3%. Among the patients
      who survived, 40 (68%) recovered to their baseline renal function at 3 months,
      most of them being classified as no AKI during the ICU stay. We have herein
      reported the evolution of renal function among kidney graft recipients after an
      ICU stay.

PMID- 23146527
TI  - Delayed graft function does not harm the future of donation-after-cardiac death
      in kidney transplantation.
AB  - INTRODUCTION: Delayed graft function (DGF) occurs more frequently in kidney
      transplants from donation after cardiac death (DCD) than from donation after
      brain death (DBD). We investigated the effect of DGF on posttransplantation
      outcomes among grafts from controlled DCD kidneys. PATIENTS AND METHODS: This
      single-center retrospective study recruited 80 controlled DCD kidneys
      transplanted from January 2005 to December 2011. Mean patient follow-up was 28.5
      months. RESULTS: There were no primary nonfunction grafts; the DGF rate was
      35.5%. Overall graft survival rates between groups with versus without DGF were
      92.4% and 95.2% at 1 year, 92.4% and 87.1% at 3 years, and 84.7% and 87.1% at 5
      years, respectively (P = not significant (NS)). Patients with versus without DGF
      showed the same survival rates at the corresponding time 92.4% vs 97.2%, 92.4% vs
      93.9%, and 84.7% vs 93.9% (P = NS). Estimated glomerular filtration rate was
      significantly lower in the DGF compared with the non-DGF group at hospital
      discharge (29 vs 42 mL/min; P = .00) and at 6 months posttransplantation (46 vs
      52 mL/min; P = .04), but the difference disappeared thereafter: 47 vs 52 mL/min
      at 1 year, 50 vs 48 mL/min at 3 years, and 54 vs 53 mL/min at 5 years (P = NS).
      DGF did not increase the risk of an acute rejection episode (29.6% vs 30.6%; P =
      NS) or rate of surgical complications (33.3% vs 26.5%; P = NS). However, DGF
      prolonged significantly the length of hospitalization in the DGF versus the non-
      DGF group (18.9 vs 13 days; P = .00). Donor body mass index (BMI) >= 30 kg/m(2),
      recipient BMI >=30 kg/m(2), and pretransplantation dialysis duration increased
      the risk of DGF upon multivariate logistic regression analysis. CONCLUSIONS:
      Apart from the longer hospital stay, DGF had no deleterious impact on the future
      of kidney allografts from controlled DCD, which showed comparable graft and
      patient survivals, renal function, rejection rates, and surgical complications as
      a group without DGF. Therefore, DGF should no longer be considered to be a
      medical barrier to the use of kidney grafts from controlled DCD.

PMID- 23146528
TI  - Risk factors for surgical complications after renal transplantation and impact on
      patient and graft survival.
AB  - PURPOSE: We report herein the incidence of and factors predisposive to surgical
      complications (SC) after renal transplantation. METHODS: Between 2004 and 2008,
      we performed 200 renal transplantation. We retrospectively studied recipient and
      donor characteristics, cold ischemia time, surgical revision in the month after
      transplantation, delayed graft function, surgical complications (vascular,
      urologic, wound, or bleeding), as well as graft and patient 5-year survival
      rates. RESULTS: Sixty-six surgical complications were reported among 49 patients
      with a preponderance of urologic complications. We noted 6.1% Clavien I, 1.5%
      Clavien II, 30.3% Clavien IIIa, 53% Clavien IIIb, and 9.1% Clavien IVa SCs.
      Vascular complications showed a worse prognosis. Among recipients, dialysis
      duration before transplantation (40.3 +/- 50.8 months in SCs versus 28 +/- 26.5
      months in the control unaffected group, P = .032) and anti-HLA immunization (34.7
      +/- 48% versus 21.2 +/- 41%, P = .05) appeared to be risk factor. No significant
      factor was identified among donors, although patients with surgical complications
      received older transplants than the control popuation (49.7 +/- 14.5 years versus
      45.5 +/- 15.1 years, P = .08). A greater percentage of delayed graft function
      (30.6 +/- 46.6% versus 11.4 +/- 31.9%; P = .001) and graft rejection episodes
      (34.7 +/- 48.1% versus 17.9 +/- 38.4%, P .013) were observed among the SC
      compared with the control group. No significant difference in patient (89.5%
      versus 95.6% confidence interval, CI 95% [0.7-10.0]; P = .14) or graft survival
      (88.7% versus 91.8%, CI 95% [0.4-3.9] P = .63) was observed between the groups.
      CONCLUSION: Surgical complications, especially urologic complications appear
      frequently after renal transplantation. Dialysis duration and pre-transplant
      immunization were linked to the occurrence of a surgical complication, which did
      not affect graft or patient survival.

PMID- 23146529
TI  - Preemptive therapy versus valgancyclovir prophylaxis in cytomegalovirus-positive
      kidney transplant recipients receiving antithymocyte globulin induction.
AB  - International consensus guidelines on the management of cytomegalovirus (CMV)
      infections in kidney transplantation recommend the use of universal prophylaxis
      over preemptive therapy for the highest risk kidney transplant recipients (KTR),
      namely donor+/recipient - CMV serostatus. However, no universal recommendations
      have been made for R+ KTR undergoing antithymocyte globulin (ATG) induction. In
      this retrospective study, we compared 1-year outcomes among 24 R+ KTR who
      received 3 months of valgancyclovir prophylaxis with 72 R+ KTR who were subjected
      to a preemptive strategy. All subjects received ATG induction. The incidence of
      CMV infection was significantly higher among the preemptive subjects versus the
      prophylaxis group (78% versus 38%, respectively; P = .0003), whereas the
      incidence of CMV disease was low and did not differ significantly between the
      cohorts (8% versus 7% respectively, P = .8). Late-onset CMV infections were only
      observed in the prophylaxis group (25% versus 0%, P = .0001). Finally, the rate
      of opportunistic infections, acute rejection episodes, and graft/patient
      survivals at 1 year were also similar between the two groups. In light of this
      study, preemptive therapy and universal prophylaxis were almost equally effective
      to prevent CMV infection among R+ KTR receiving ATG induction.

PMID- 23146530
TI  - Disseminated varicella zoster virus infection in adult renal transplant
      recipients: outcome and risk factors.
AB  - BACKGROUND: Disseminated varicella zoster virus (VZV) infection, whether due to
      primary infection or reactivation, may be life threatening in renal transplant
      recipients. The aims of this study were to assess the outcome of disseminated VZV
      infection in renal transplant recipients and to determine potential risk factors
      for mortality. METHODS: A search of the English literature from 1985 to 2011
      using PUBMED was performed. Reports involving renal transplant recipients younger
      than 16 years of age were excluded. RESULTS: A total of 56 adult patients
      presenting with a disseminated cutaneous or visceral VZV infection was included.
      Seventy percent of cases occurred within 5 years after transplantation, and 89%
      within 10 years. Visceral complications including disseminated intravascular
      coagulation occurred in two thirds of patients. Mortality decreased significantly
      from 47% in the era before 1995 to 17% after 1995 (P = .04). Risk factors for
      mortality included visceral involvement, use of azathioprine as
      immunosuppressant, and longer time between transplantation and VZV infection. VZV
      seropositivity did not influence fatal outcome. CONCLUSION: Disseminated VZV
      infection can be life threatening in renal transplant recipients with a global
      mortality rate of 30%. This rate seems to have decreased since 1995. Seropositive
      VZV patients with disseminated infection are not protected from fatal outcome.

PMID- 23146531
TI  - An epidemic of Pneumocystis jiroveci pneumonia in a renal transplantation center:
      role of T-cell lymphopenia.
AB  - Although only 2 cases of Pneumocystis jiroveci pneumonia were observed in our
      center between 2004 and 2009, we diagnosed 9 cases in 2010. Each patient had been
      in contact in the hospital with at least 1 other patient suffering P jiroveci
      pneumonia. Genotyping of P jiroveci pneumonia strains demonstrates a total
      homogeneity of the DNA sequences in the 7 patients already analyzed. CD4+
      lymphocyte count was significantly lower at M3 in P jiroveci pneumonia patients
      than in controls. Our clinical and molecular data confirm that interhuman
      transmission of P jiroveci is possible, particularly to lymphopenic transplant
      recipients.

PMID- 23146532
TI  - Is renal allograft dysfunction a risk factor for severe infection in kidney
      transplant recipients?
AB  - The ANTICIPE study is a cross-sectional, multicenter, French study. The aim of
      this study was to describe clinical and biological parameters observed in a
      cohort of 1446 stable renal transplant recipients, according to the stage of
      chronic kidney disease. Severe infection was defined as an infection
      necessitating >= 7 days of hospital stay. We observed a negative correlation
      between declining glomerular filtration rate and occurrence of severe infection
      (P < .0001). In multivariate analysis, severe infection was associated with age,
      female gender, chronic kidney disease stage (Kidney Disease Outcomes Quality
      Initiative classification), and number of acute rejection episodes. Our study
      suggested that renal allograft function is a predictor not only of cardiac death
      and cardiovascular complications, but also of severe infections.

PMID- 23146533
TI  - Sirolimus for the treatment of Kaposi sarcoma after renal transplantation: a
      series of 10 cases.
AB  - The incidence of Kaposi sarcoma (KS) has substantially increased among
      immunocompromised patients, suggesting a role for immunosuppressive drugs. The
      aim of this study was to evaluate the incidence, features, and outcome of KS
      among 307 kidney transplantation patients at our center between January 1994 and
      June 2010. During the study period, the 10 patients who developed KS (3.25%)
      showed a mean age at transplantation of 35.8 +/- 8.7 years (range, 22 to 49
      years). The mean interval between transplantation and occurrence of KS was 24.7
      +/- 21.36 months (range, 6 to 64 months). The mean time of antithymocyte globulin
      induction was 9.5 days (range, 6 to 13 days). KS was restricted to the skin in 7
      cases, among which, one presented with associated Hodgkin lymphoma. Visceral
      involvement (one lung and one colon) was observed in two cases. One patient
      presented with a gastric KS without skin lesions. Immunosuppressive treatment was
      reduced, then withdrawn in three cases, resulting in regression of KS a few weeks
      later, but with graft loss requiring hemodialysis at 1, 3 and 4 months. Among the
      remaining 7 cases, we stopped mycophenalate mofetil (MMF) and switched from
      calcineurin inhibitors to sirolimus. Allograft function remained stable after the
      switch. Only one patient who already had allograft dysfunction due to biopsy
      proven chronic allograft nephropathy. Deteriorated progressively, undergoing
      hemodialysis at 2 years after KS diagnosis. In conclusion, we observed a
      relatively high incidence of KS among our cases. The introduction of sirolimus
      resulted in complete regression of KS lesions with preserved graft function.

PMID- 23146534
TI  - Circulating and intragraft TH17 cells are not increased at the early stage of
      chronic allograft nephropathy.
AB  - Since TH17 cells could play a role in the pathogenesis of allograft nephropathy,
      we investigated them in peripheral blood and kidney allograft infiltrates. We
      compared percentages of TH17 cells and IL17A in peripheral blood of 14 kidney
      allograft recipients and 8 healthy volunteers. Allograft recipients experiencing
      graft dysfunction and kidney biopsy specimens showing chronic allograft
      nephropathy (CAN) were distinguished from a "control group," both of which were
      tested for TH17 and CD15+ staining. Allograft recipients displayed a
      significantly lower percentage of TH17 cells and IL17A blood levels than healthy
      volunteers, suggesting effects of the immunosuppressive regimen. No difference in
      these values was observed between the CAN group and the control group. On kidney
      allograft biopsies, CD15+ infiltrate was significantly higher in the CAN group
      than in the control group. In CAN, IL17 secretion might play a chemoattractant
      role for neutrophils. However, these preliminary data have to be confirmed in
      larger studies.

PMID- 23146535
TI  - Evolution of native kidney function after pancreas transplantation alone.
AB  - INTRODUCTION: This study investigated changes in kidney function over time among
      a cohort of patients undergoing pancreas transplantation alone (PTA) from January
      2002 to December 2011. PATIENTS AND METHODS: Ten of eighteen PTA patients bearing
      functioning grafts for at least 1 year were recruited for the analysis. Primary
      endpoints were changes in mean serum creatinine (SCr, mg/L) and mean estimated
      glomerular filtration rate (eGFR) using the 4-variable Levey-MDRD equation
      (mL/min/1.73 m(2)) comparing baseline (pretransplantation) to 6-month, 1-year, 3
      year, and 5-year posttransplantation values. Mean follow-up time was 75.7 +/-
      20.5 months (range, 46-106.5). RESULTS: Baseline eGFR was 89.3 +/- 27.9 (range,
      58-145). eGFR decreased to 75.7 +/- 26.2, 71 +/- 20.6, 66.5 +/- 14.8, and 62.1 +/
      11.2 at 6 months, 1, 3, and 5 years representing -15.2%, -20.5%, -15.8%, and 
      22.6% percentage decreases respectively (P < .05 for all pairwise comparisons).
      The Baseline SCr was 8.6 +/- 2.3 mg/L (range, 5-13). SCr progressively increased
      to 10.1 +/- 3, 10.5 +/- 3.1, 10.9 +/- 3.1, and 11.3 +/- 1.7 at 6 months, 1, 3,
      and 5 years a 17.1%, 22%, 16.6%, and 19.9% increase respectively (P < .05 for all
      pairwise comparisons). One of ten, 2/8, and 3/7 patients displayed an eGFR <60 at
      transplantation versus 3 and 5 years thereafter, respectively. No patient
      developed a SCr > 25 mg/L or eGFR <30 or needed dialysis or kidney
      transplantation. Five of ten patients had micro-albuminuria or proteinuria before
      transplantation. Tacrolimus levels were within recommended therapeutic ranges
      over time. CONCLUSION: Kidney function deteriorated significantly after PTA.
      Understanding of risk factors for the development of renal impairment is
      important to preserve kidney function and to select appropriate candidates for
      PTA.

PMID- 23146536
TI  - Corticosteroids do not reverse the inhibitory effect of cyclosporine on
      regulatory T-cell activity in contrast to mycophenolate mofetil.
AB  - BACKGROUND: Inevitable hepatitis C virus recurrence after liver transplantation,
      a major barrier to survival of the transplanted liver may be promoted by
      immunosuppression and by CD4(+)CD25(+) regulatory T cells (Treg). Treg cells are
      essential for the induction and maintenance of immunologic self-tolerance as well
      as transplant tolerance. Moreover, we have previously described low doses of
      cyclosporine (CsA) to inhibit Treg activity by inducing interleukin-2 and
      interfron-gamma. We investigated here in, the effect of mycophenolate mofetil
      (MMF) and corticosteroids, usually used in combination with a calcineurin
      inhibitor on human CD4(+)CD25(+) Treg cells. METHODS: Human CD4(+)CD25(+) cells
      isolated from healthy donors were cultured in the presence of CsA +/- corticoids
      or MMF. Suppressive activity of regulatory T cells was assessed in mixed
      leukocyte reactions including CD25(+) solvents with autologous activated
      peripheral blood mononuclear cells (PBMC). RESULTS: MMF and dexamethasone
      inhibited PBMC and Treg proliferation in dose-dependent fashing, maintaining the
      suppressive activity of Treg cells. However, the association of corticoids with
      CsA could not reverse the inhibitory effects of CsA on Treg activity, unlike the
      MMF and CsA combination. CONCLUSION: We have previously shown CsA to
      significantly impair the function of CD4(+)CD25(+) Treg cells. Herein we reports
      that corticoids were not able to reverse this effect, whereas MMF couterbalanced
      it, suggesting that the combination of MMF with CsA maintains regulatory T cells
      activity promoting tolerance.

PMID- 23146537
TI  - Impact of interleukin-2-expanded regulatory T cells in various allogeneic
      combinations on mouse skin graft survival.
AB  - The impact of in vivo regulatory T cells (Treg) expansion using short-term
      injections of interleukin-2 (IL-2) coupled to a specific anti-IL-2 antibody was
      examined in various allogeneic combinations of murine skin transplantations. In a
      model of a single major histocompatibility complex (MHC) class II disparity, the
      IL-2-expanded Tregs infiltrated the transplanted skin, inhibited Th1
      alloreactivity, and prevented acute graft rejection. However, in the presence of
      increased load of CD4-recognized alloantigens, exogenous IL-2 only moderately
      prolonged graft survival as attested by CD8 T cell-depletion in full minor plus
      major mismatched recipients treated with IL-2. If direct CD8 alloreactivity
      remained intact, the IL-2/anti-IL-2-mediated Tregs expansion failed to delay
      allograft rejection. This observation was confirmed by the inability of expanded
      Tregs to delay rejection of multiple minor disparate (MHC matched) skin
      allografts. Altogether, these results warn that cross-reactive CD8(+) T cells
      represent an important hurdle to Treg-based tolerance induction.

PMID- 23146538
TI  - PARVG gene polymorphism and operational renal allograft tolerance.
AB  - A unique blood transcriptional profile of 49 genes has been previously
      highlighted that may be used to distinguish drug-free operationally tolerant
      kidney recipients (TOL) from other kidney recipients with contrasted clinical
      situations and healthy volunteers. The aim of this study was to investigate
      whether the pattern of these 49 genes could be influenced by genetic
      polymorphisms located in the corresponding genomic sequences and whether some of
      these single nucleotide polymorphisms (SNPs) could be associated with clinical
      status of kidney transplant recipients. In this study, 1152 candidate tag SNPs
      spanning these genes were genotyped using a Golden Gate Illlumina assay in a
      sample of 164 kidney transplant recipients, including 11 operationally tolerant
      patients, 134 patients with stable graft function, 19 with proven signs of
      chronic rejection, and 27 healthy volunteers. The gene expression and clinical
      status were studied according to the different SNPs. Among the genes
      demonstrating expression difference between TOL compared with CR&STA patients,
      PARVG, which is a member of a family of actin-binding proteins associated with
      focal contacts, stands out with 2 SNPs, (rs139144 and rs5764592) explaining about
      20% of the gene expression variability. Linkage disequilibrium analysis of these
      2 SNPs showed the rs139144GG genotype was associated with decreased PARVG
      expression and was numerically more frequent in TOL (60%) than in CR&STA (28%)
      patients (P = .068). These preliminary results, which should be confirmed in a
      larger population, open new perspective of regulation pathways and hypothesis in
      operational tolerance mechanism.

PMID- 23146539
TI  - Atypical presentation of a brown tumor in a kidney transplant recipient: a case
      report.
AB  - Brown tumor is a rare complication of secondary hyperparathyroidism. It is
      exceptionally encountered after kidney transplantation. We here report on a 54
      year-old male recipient who developed a brown tumor localized in the right
      forearm, and whose initial presentation was atypical, mimicking a bone tumor.
      Hence, diagnosis of brown tumors should be suggested by clinicians in a context
      of hyperparathyroidism.

PMID- 23146540
TI  - Severe colchicine intoxication in a renal transplant recipient on cyclosporine.
AB  - Using colchicine to treat an acute gout crisis in an organ transplant recipient
      (TR) on cyclosporine (CsA) may result in life-threatening intoxication. We report
      the case of a 59-year-old kidney transplant recipient on CsA who was treated with
      colchicine for acute gout crisis. Seven days later, he developed rhabdomyolysis
      with progressive quadriparesis, hematologic toxicity and acute renal failure. CsA
      inhibits P-glycoprotein resulting in decreased hepatic metabolism and renal
      excretion of colchicine. Colchicine and CsA withdrawal as well as appropriate
      supportive treatments were effective to manage all of these complications.

PMID- 23146541
TI  - Organ donation in Belgium 2011: the highest donation rate ever.

PMID- 23146542
TI  - Risk factors for bleeding and clinical implications in patients undergoing liver
      transplantation.
AB  - INTRODUCTION: Advanced liver disease is characterized by prolonged global
      coagulation tests such as prothrombin time (PT). Using Model of End-stage Liver
      Disease (MELD) score-based allocation, many current transplant recipients show
      advanced end-stage liver disease with an elevated international normalized ratio
      (INR). The relationship between abnormalities in coagulation tests and the risk
      of bleeding has been recently challenged among liver disease patients. In this
      study we reassessed risk factors for bleeding and the clinical implications for
      patients who underwent orthotopic liver transplantation (OLT). METHODS: We
      studied OLT patients between 2005 and 2011 excluding combined transplantations,
      retransplantations, or cases due to acute liver failure. We collected
      prospectively pre-OLT, during OLT, and post-OLT clinical and biochemical data to
      assess the risk for bleeding using linear regression models. RESULTS: The
      strongest predictor of overall survival among 286 patients with a mean follow-up
      of 32 months was the number of blood transfusions (P = .005). The risk factor for
      bleeding during surgery investigated by multivariate analysis only showed the INR
      (P < .001) and the presence of ascites (P = .003) to independently correlate with
      the amount of blood transfusion. Receiver operation characteristics (ROC)
      analysis performed to determine the risk for massive blood transfusion (more than
      6 units) revealed a cut-off value for INR >= 1.6. Appreciation of the operative
      field by the surgeon during the intervention as "wet" versus "dry", amounts of
      blood transfusion and fresh frozen plasma, and stay in the intensive care unit
      (ICU) and in the hospital were all significantly different (P < .001) for
      patients with INR <1.6 versus INR >= 1.6. CONCLUSIONS: Bleeding during OLT
      affects the outcome. The risk is independently influenced by the presence of
      ascites (probably reflecting the degree portal hypertension) and an INR >= 1.6.
      To improve survival after OLT therapeutic interventions should be further
      explored to reduce the need for blood transfusions.

PMID- 23146543
TI  - Septuagenarian and octogenarian donors provide excellent liver grafts for
      transplantation.
AB  - BACKGROUND: Wider utilization of liver grafts from donors >= 70 years old could
      substantially expand the organ pool, but their use remains limited by fear of
      poorer outcomes. We examined the results at our center of liver transplantation
      (OLT) using livers from donors >= 70 years old. METHODS: From February 2003 to
      August 2010, we performed 450 OLT including 58 (13%) using donors >= 70 whose
      outcomes were compared with those using donors <70 years old. RESULTS:
      Cerebrovascular causes of death predominated among donors >= 70 (85% vs 47% in
      donors <70; P < .001). In contrast, traumatic causes of death predominated among
      donors <70 (36% vs 14% in donors >= 70; P = .002). Unlike grafts from donors <70
      years old, grafts from older individuals had no additional risk factors
      (steatosis, high sodium, or hemodynamic instability). Both groups were comparable
      for cold and warm ischemia times. No difference was noted in posttransplant peak
      transaminases, incidence of primary nonfunction, hepatic artery thrombosis,
      biliary strictures, or retransplantation rates between groups. The 1- and 5-year
      patient survivals were 88% and 82% in recipients of livers <70 versus 90% and 84%
      in those from >= 70 years old (P = .705). Recipients of older grafts, who were 6
      years older than recipients of younger grafts (P < .001), tended to have a lower
      laboratory Model for End-Stage Liver Disease score (P = .074). CONCLUSIONS: Short
      and mid-term survival following OLT using donors >= 70 yo can be excellent
      provided that there is adequate donor and recipient selection. Septuagenarians
      and octogenarians with cerebrovascular ischemic and bleeding accidents represent
      a large pool of potential donors whose wider use could substantially reduce
      mortality on the OLT waiting list.

PMID- 23146544
TI  - Outcomes of liver transplantations using donations after circulatory death: a
      single-center experience.
AB  - INTRODUCTION: Orthotopic liver transplantation (OLT) (LTx) using donation after
      circulatory death (DCD) donors is increasingly performed, but still considered to
      risk of poorer outcomes compared with standard donations after brain death (DBD)
      OLT. Therefore we reviewed our results of DCD-OLT. PATIENTS AND METHODS: Between
      2003 and 2010, we performed 30 DCD-OLT (6% of all OLT). We retrospectively
      reviewed medical records of donors and recipients after DCD versus DBD-OLT to
      analyze biliary complications, retransplantation rates, and patient/graft
      survivals. RESULTS: Median donor age was similar for DCD and DBD-OLT: 51 versus
      53 years (P = .244). Median donor warm ischemia time (stop ventilation to cold
      perfusion in DCD donors) was 24 minutes. Median cold ischemia time was shorter
      for DCD (6 hours 54 minutes) compared with DBD-OLT (8 hours 36 minutes; P <
      .0001). Median laboratory model of end-stage liver disease score was 15 for DCD,
      and 16 for DBD-OLT (P = .59). Median post-OLT Aspartate Aminotransferase (AST)
      peak was higher after DCD: 1178 versus DBD-OLT 651 IU/L (P = .005). The incidence
      of nonanastomotic strictures was different: 33.3% for DCD versus 12.5% for DBD
      OLT (P = .001). The overall retransplantation rate was 3% after both DCD and DBD
      OLT. After DCD-LTx actuarial 1, 3- and 5-year patient survivals were 93, 85 and
      85%, and corresponding graft survivals, 90%, 82%, and 82% respectively, and not
      different compared with DBD-OLT: 88%, 78%, and 72% (P = .348) and 85%, 74%, and
      68% (P = .524) respectively. CONCLUSION: Despite substantial ischemic injury
      (high peak AST and biliary strictures) short- and long-term survival after DCD
      OLT was comparable to DBD-OLT. Rapid donor surgery, careful donor and recipient
      selection, as well as short warm and cold ischemia times are key factors to
      optimize outcomes after DCD-OLT. However, strategies to reduce biliary
      complications remain warranted.

PMID- 23146545
TI  - Potentiation of adverse effects of cold by warm ischemia in circulatory death
      donors for porcine liver transplantation.
AB  - BACKGROUND: Wider use of donors after circulatory death (DCD) could reduce
      mortality on the liver transplantation waiting list. We previously reported that
      pig livers exposed to >= 30 minutes of warm ischemia followed by 4 hours of cold
      ischemia are at high risk of primary graft nonfunction. We sought to determine
      how prolonged cold ischemia, after a short, normally well-tolerated period of
      warm ischemia affects graft function and recipient survival using a porcine model
      of liver transplantation. MATERIALS AND METHODS: Livers were transplanted after
      exposure to no warm plus 4 hours cold ischemia (group 1); 15 minutes of warm and
      4 hours of cold ischemia (group 2); no warm and 8 hours of cold ischemia (group
      3); or 15 minutes of warm and 8 hours of cold ischemia (group 4). Recipient
      survival, graft dysfunction incidence, liver function (prothrombin time),
      hepatocellular damage (aspartate aminotransferase), sinusoidal cell function
      (hyaluronic acid), and inflammation (tumor necrosis factor-alpha) were recorded
      after transplantation. Biopsies were scored for ischemia-reperfusion injury.
      RESULTS: Day 4 survival in group 4 was 0% versus 100%, 83%, and 100% in groups 1,
      2, and 3, respectively. Recipients in group 4 exposed to short warm but prolonged
      cold ischemia displayed severe graft dysfunction, the highest peak transaminase,
      the greatest inflammatory response, more sinusoidal endothelial cell dysfunction
      and, the worst histologic score for ischemia-reperfusion injury. CONCLUSIONS:
      Liver grafts from DCD donors, even when exposed to short periods of warm
      ischemia, did not tolerate prolonged cold ischemia well and should be
      transplanted without delay.

PMID- 23146546
TI  - Correlations between cyclosporine concentrations at 2 hours post-dose and trough
      levels with functional outcomes in de novo lung transplant recipients.
AB  - BACKGROUND: Although the reliability of cyclosporine (CyA) concentration at 2
      (C2) hours postdosing has been established for kidney, liver, and heart
      transplant recipients, its use in lung cases remains to be validated. We
      investigated the relationship between CyA dual time point monitoring and long
      term functional outcomes after lung transplantation. METHODS: We included data
      from 38 lung transplant recipients receiving CyA, azathioprins, and steroids in
      the study. CyA dosages were based on the trough concentrations. CyA
      concentrations at 0 (C0) and 2 (C2) hours postdosing were obtained at 1, 2, 3, 6,
      9, 12, 15, 18, and 24 months postoperative. We retrospectively compared average
      CyA level (C0 and C2) during the first 3 posttransplantation months with forced
      expiratory volume in 1 second (FEV1), forced vital capacity (FVC), forced
      expiratory flow 25%-75 % (FEF 25-75), creatinine, systolic blood pressure (SBP),
      and diastolic blood pressure (DBP) using regression analysis via generalized
      estimating equations (GEE). RESULTS: Only improvement in FVC (P = .033) and
      deterioration of SBP (P < .001) were related to C0 monitoring. No correlation was
      observed between C0 and FEV1 (P = .13), FEF 25-75 (P = .48), creatinine (P =
      .07), and DBP (P = .97). Nor was any relationship observed between C2
      concentrations and FEV1 (P = .64), FVC (P = .38), FEF 25-75 (P = .09), creatinine
      (P = .95), SBP (P = .73), or DBP (P = .51). CONCLUSION: There was a lack of a
      relationship between CyA concentrations (C0 and C2) and functional outcomes among
      de novo lung transplantations except for a positive correlation of 0 value with
      long-term improved FVC and increased SBP. This study suggested that C2
      determinations may not improving lung recipient management.

PMID- 23146547
TI  - Liver transplantation in a patient with an intraabdominally located left
      ventricular assist device: surgical aspects--case report.
AB  - The presence of a cardiac assist device in a liver transplantation candidate
      should not be considered to be an absolute contraindication to transplantation.
      In this first case report of liver transplantation in a patient with an
      intraabdominally located left ventricular assist device, we have described the
      surgical aspects and discussed the timing of the liver transplantation and the
      removal of the left ventricular assist device.

PMID- 23146548
TI  - Gastric outlet obstruction by a donor aortic tube after en bloc liver pancreas
      transplantation: a case report.
AB  - We present the case of a 30-year-old female suffering from a type five maturity
      onset diabetes of the young deficiency, resulting in type 1 diabetes and terminal
      renal insufficiency. She also had chronic and refractory pruritis due to primary
      sclerosing cholangitis-like fibrosis. She underwent combined en bloc liver and
      pancreas transplantation and kidney transplantation. The postoperative course was
      complicated by a gastric outlet obstruction due to compression of the native
      gastroduodenal junction by the donor aortic tube. This was treated by
      construction of a roux-en-Y gastrojejunostomy at posttransplant day 24. To our
      knowledge, compression of the gastroduodenal junction by a donor aortic tube
      after combined liver and pancreas (or multivisceral) transplantation has not been
      reported previously.

PMID- 23146550
TI  - Multi-channel electromyography during maximal isometric and dynamic contractions.
AB  - Motor unit behavior differs between contraction types at submaximal contraction
      levels, however is challenging to study during maximal voluntary contractions
      (MVCs). With multi-channel surface electromyography (sEMG), mean physiological
      characteristics of the active motor units can be extracted. Two 8-electrode sEMG
      arrays were attached on biceps brachii muscle (one on each head) to examine
      behavior of sEMG variables during isometric, eccentric and concentric MVCs of
      elbow flexors in 36 volunteers. On average, isometric (364 +/- 88N) and eccentric
      (353 +/- 74N) MVCs were higher than concentric (290 +/- 73N) MVC (p < 0.001).
      Mean muscle fiber conduction velocity (CV) was highest during eccentric MVC (4.42
      +/- 0.49 m/s) than concentric (4.25 +/- 0.49 m/s, p < 0.01) and isometric (4.14
      +/- 0.45 m/s, p < 0.001) MVCs. Furthermore, eccentric MVC showed lower sEMG
      amplitude at the largest elbow joint angles (120-170 degrees ) and higher CV at
      the smallest (70-150 degrees ) elbow joint angles ( p < 0.05-0.001) than
      concentric MVC. The differences in CV and sEMG amplitude between the MVCs suggest
      that the control strategy of motor units differs between the contraction types
      during MVCs, and is dependent on the muscle length between the dynamic MVCs.

PMID- 23146549
TI  - Diet quality and weight change among overweight and obese postpartum women
      enrolled in a behavioral intervention program.
AB  - BACKGROUND: Postpartum weight retention is a risk factor for long-term weight
      gain. Encouraging new mothers to consume a healthy diet may result in weight
      loss. OBJECTIVE: To assess predictors of diet quality during the early postpartum
      period; to determine whether diet quality, energy intake, and lactation status
      predicted weight change from 5 to 15 months postpartum; and to determine whether
      an intervention improved diet quality, reduced energy intake, and achieved
      greater weight loss compared with usual care. DESIGN: Randomized clinical trial
      (KAN-DO: Kids and Adults Now-Defeat Obesity), a family- and home-based, 10-month,
      behavioral intervention to prevent childhood obesity, with secondary aims to
      improve diet and physical activity habits of mothers to promote postpartum weight
      loss. PARTICIPANTS: Overweight/obese, postpartum women (n=400), recruited from 14
      counties in the Piedmont region of North Carolina. INTERVENTION: Eight education
      kits, each mailed monthly; motivational counseling; and one group class. METHODS:
      Anthropometric measurements and 24-hour dietary recalls collected at baseline
      (approximately 5 months postpartum) and follow-up (approximately 10 months
      later). Diet quality was determined using the Healthy Eating Index-2005 (HEI
      2005). STATISTICAL ANALYSES: Descriptive statistics, chi(2), analysis of
      variance, bi- and multivariate analyses were used. RESULTS: At baseline, mothers
      consumed a low-quality diet (HEI-2005 score=64.4 +/- 11.4). Breastfeeding and
      income were positive, significant predictors of diet quality, whereas body mass
      index was a negative predictor. Diet quality did not predict weight change.
      However, total energy intake, not working outside of the home, and breastfeeding
      duration/intensity were negative predictors of weight loss. There were no
      significant differences in changes in diet quality, decreases in energy intake,
      or weight loss between the intervention (2.3 +/- 5.4 kg) and control (1.5 +/- 4.7
      kg) arms. CONCLUSIONS: The family-based intervention did not promote postpartum
      weight loss. Reducing energy intake, rather than improving diet quality, should
      be the focus of weight-loss interventions for overweight/obese postpartum women.

PMID- 23146551
TI  - Measurement of synergy and spasticity during functional movement of the post
      stoke hemiplegic upper limb.
AB  - The aim of the present study was to measure the muscle-contraction patterns of
      the hemiplegic upper limb using electromyography (EMG) and to investigate the
      relationship between muscle co-contraction and functional recovery in stroke
      patients presenting with synergy and spasticity. The muscle-contraction patterns
      of the upper limb of 12 chronic stroke patients and 10 normal volunteers were
      measured, and the co-contraction in the distal and proximal muscles was
      simultaneously quantified, while the participants performed hand-grasp and
      shoulder flexion tasks. The spasticity and hemiplegic arm function were
      evaluated, respectively, on a modified Ashworth scale (MAS) and by means of Fugl
      Meyer motor assessment (FMA). The correlation between the MAS and FMA values was
      analyzed. Increased co-contraction (66-555%) was observed in both the proximal
      and distal upper limbs, and was positively correlated with spasticity of the
      elbow flexor (r = 0.944 on shoulder flexion, r = 0.741 on hand grasping, p <
      0.01) and negatively correlated with functional recovery of the upper limb (r = 
      0.670 ~ -0.884, p < 0.05). Specific movement patterns influenced by synergy and
      spasticity were confirmed by EMG. These results might prove useful to the
      formulation of appropriate management plans such as those involving botulinum
      toxin injection or nerve block.

PMID- 23146552
TI  - Exertional muscle pain in familial Mediterranean fever patients evaluated by MRI
      and 31P magnetic resonance spectroscopy.
AB  - AIM: To evaluate the effect of physical activity on the structural,
      morphological, and metabolic characteristics of the gastrocnemius muscle in
      familial Mediterranean fever (FMF) patients, utilizing quantitative (31)P
      magnetic resonance spectroscopy (MRS), in order to elucidate the mechanism of
      their exertional leg pain. MATERIALS AND METHODS: Eleven FMF patients suffering
      from exertional leg pain (eight male, three female; mean age 33 years) and six
      healthy individuals (three male, three female; mean age 39 years) constituted the
      control group. All of the participants underwent magnetic resonance imaging (MRI)
      and non-selective (31)P MRS (3 T) of the leg muscles before and after graded
      exercise on a treadmill. Phosphocreatine (PCr):inorganic phosphate (Pi),
      PCr:adenosine triphosphate (ATP) ratios and the intracellular pH of the leg
      muscles were measured using (31)P MRS. RESULTS: For both groups, normal muscle
      mass with no signal alterations was observed on the MRI images after exercise.
      The normal range of pre- and post- exercise MRS muscle parameters was observed in
      both groups. However, the intracellular pH post-exercise, was significantly
      higher (less acidic) in the FMF group compared to the control group [pH (FMF) =
      7.03 +/- 0.02; pH (control) 7.00 +/- 0.02; p < 0.0006]. CONCLUSIONS: The finding
      of a less prominent, post-exercise acidification of the gastrocnemius muscle in
      this FMF patient group suggests a forme fruste of glycogenosis. This preliminary
      observation should be further investigated in a future, larger-scale study.

PMID- 23146553
TI  - Radiographic and pathological analysis of small lung adenocarcinoma using the new
      IASLC classification.
AB  - AIM: To analyse the correlation between computed tomography (CT) findings of
      small lung adenocarcinomas and the International Association for the Study of
      Lung Cancer/American Thoracic Society/European Respiratory Society Classification
      of Lung Adenocarcinoma. MATERIALS AND METHODS: A retrospective review of 300 lung
      adenocarcinoma lesions (size <=20 mm) after surgical resection in 295 consecutive
      patients was performed. Tumours were defined as air-containing type if the ratio
      of the maximum dimension of the tumour on mediastinal windows to the maximum
      dimension of the tumour on lung windows was <=50%, and as solid-density type if
      the ratio was >50%. The incidence between CT findings (air bronchogram, vascular
      involvement, pleural tags, notches, and spiculation) and pathological findings
      were investigated. RESULTS: Of the 142 air-containing lesions, 114 were
      adenocarcinoma in situ (AIS), 28 were minimally invasive adenocarcinoma (MIA),
      and none of the lesions were invasive adenocarcinoma. Of the 158 solid-density
      lesions, 30 were AIS, 24 were MIA, and 104 were invasive adenocarcinoma. Notches
      and pleural tags were commonly observed in cases of invasive adenocarcinoma (p <
      0.05). CONCLUSIONS: In the air-containing type of small lung adenocarcinomas, AIS
      and MIA were observed but no cases of invasive adenocarcinoma were found. The
      presence of notches and pleural tags were a significant factor in invasive
      adenocarcinoma.

PMID- 23146554
TI  - Bipolar radiofrequency ablation for symptomatic giant (>10 cm) hepatic cavernous
      haemangiomas: initial clinical experience.
AB  - AIM: To describe initial clinical experience with bipolar radiofrequency ablation
      (RFA) for symptomatic giant hepatic haemangiomas. MATERIALS AND METHODS: Four
      consecutive patients with a large-volume, symptomatic hepatic cavernous
      haemangioma of >10 cm were treated with bipolar RFA during laparotomy with
      ultrasound guidance. Complications were carefully noted. Clinical and
      radiological effectiveness were evaluated comparing baseline with 3 and 6 months
      follow-up of symptom assessments and upper abdominal magnetic resonance imaging
      (MRI) or computed tomography (CT). RESULTS: RFA was successfully performed for
      all four giant haemangiomas. No major complications were observed. Peri
      procedural shrinking was remarkable and intermediate-term volume reduction ranged
      from 58-92% after 6 months. Symptom relief after 6 months was complete in two
      patients and considerable in the other two. CONCLUSION: Preliminary results
      suggest intra-operative bipolar RFA to be a safe, feasible, and effective
      technique for treatment of giant symptomatic hepatic cavernous haemangiomas.

PMID- 23146555
TI  - Identifying poor compliance with CPAP in obstructive sleep apnoea: a simple
      prediction equation using data after a two week trial.
AB  - INTRODUCTION: It is important to identify those patients with OSA who are likely
      to benefit from long term CPAP, not only for symptomatic relief, but also
      potentially to reduce vascular morbidity and mortality, but are unlikely to
      adhere to treatment. We have validated a model which we developed previously for
      predicting long term compliance with CPAP using data after a 2 week trial.
      METHODS: The model was applied retrospectively to patients undergoing a trial of
      CPAP. Predicted outcomes were compared with the actual outcomes. RESULTS:
      Prediction equation was applied to 448 patients [77% males, Age 53 +/- 11 years,
      ESS 14 +/- 4, AHI 37 +/- 24]. Of 407 patients included in the study 333 were
      issued a CPAP and 74 declined long term CPAP. At one year, 81% patients were
      using CPAP at least 2 h and 70% > 4 h. A score >50% from the equation was
      associated with a high probability of CPAP usage at one year. 295 patients had a
      probability score of >50% and of them 84% were using CPAP satisfactorily at 1
      year. The sensitivity in identifying compliers was 91%. Of the 112 patients with
      a score <=50%, 38 opted to accept CPAP and 60% of them were still using it at 1
      year. CONCLUSIONS: This simple equation has now been validated to be highly
      sensitive in identifying long term compliers and it also identifies those with
      worse compliance. This group could be targeted for a more intensive follow up
      regime with the aim of improving their compliance.

PMID- 23146556
TI  - The complex link between severity of asthma and rhinitis in mite allergic
      patients.
AB  - AIM: The aim of the study was to evaluate the link between the severity of upper
      and lower airways diseases in mite allergic patients with respiratory allergy.
      PATIENTS AND METHOD: A multicentre, observational, cross-sectional study was
      carried out in 556 consecutively enrolled mite allergic patients with rhinitis
      and asthma comorbidity attending a specialist unit. Severity assessment of
      rhinitis and asthma was evaluated in accordance with ARIA and GINA guidelines.
      RESULTS: Reliable data were available for 518 patients. The distribution of
      rhinitis severity was: 15.6% mild intermittent rhinitis, 4.4% moderate-severe
      intermittent rhinitis, 30.3% mild persistent rhinitis and 49.6% moderate
      persistent rhinitis. The distribution of asthma severity was: 41.3% mild
      intermittent asthma, 14.3% mild persistent asthma, 19.1% moderate persistent
      asthma and 25.3% severe persistent asthma. In patients with moderate-severe
      persistent rhinitis (49.5%) a significant trend (p = 0.005) was found pointing to
      an increased link with asthma severity. CONCLUSION: A link between respective
      severities of rhinitis and asthma was found in only half of mite allergic
      patients with rhinitis and asthma.

PMID- 23146557
TI  - HLA-G5 in the blood of leukemia patients and healthy individuals.
AB  - In this work we focused on analysis of HLA-G5 molecules in the blood of patients
      with B-CLL leukemia and healthy individuals. Using sandwich ELISA, we found total
      soluble HLA-G, represented by sHLA-G1 and HLA-G5 in most of B-CLL patients while
      HLA-G5 alone was present only in few cases in both groups. These results lead us
      to assume that the majority of soluble HLA-G in blood is generated by proteolytic
      cleavage and shedding of membrane-bound HLA-G1. There is no correlation between
      the presence of HLA-G5 in blood of B-CLL patients and the stage of disease, age,
      and gender.

PMID- 23146558
TI  - CD11b expression and MK+ AML: a sign of impending doom?

PMID- 23146559
TI  - Conquest Pro 12 coronary guidewire for perforation of functionally interrupted
      aorta.

PMID- 23146560
TI  - Cannabis withdrawal in chronic cannabis users with schizophrenia.
AB  - BACKGROUND: Chronic users of cannabis often report withdrawal symptoms after
      abstinence from use, but little is known about cannabis withdrawal in people with
      schizophrenia. METHODS: Cannabis use patterns and withdrawal symptoms in adults
      with schizophrenia who had at least weekly cannabis use before attempting to quit
      without formal treatment were assessed with the Marijuana Quit Questionnaire
      (MJQQ), a 176-item, semi-structured questionnaire. RESULTS: 120 participants,
      predominantly African-American (62.5%) and male (76.7%), met inclusion criteria.
      20.1% reported that their first regular cannabis use (median age 15 years [range
      8-48]) preceded their age at first psychotic symptoms (20 [4-50] years). Twenty
      (16.7%) participants met lifetime criteria for cannabis abuse; 98 (81.7%) met
      surrogate criteria for lifetime cannabis dependence. Withdrawal symptoms were
      reported by 113 (94.2%) participants, with 74.2% reporting >=4 symptoms. The most
      frequently reported withdrawal symptoms were craving for cannabis (59.2%),
      feeling anxious (52.57%), feeling bored (47.5%), feeling sad or depressed
      (45.8%), feeling irritable or jumpy (45.0%), feeling restless (43.3%), and
      trouble failing asleep (33.3%). One hundred-and-four (92.0%) participants took
      some action to relieve at least one of their withdrawal symptoms during their
      index-quit attempt, including 26 (23.0%) participants who reported resuming
      cannabis use. CONCLUSION: Cannabis withdrawal is a clinically significant feature
      of cannabis use among people with schizophrenia, may serve as a negative
      reinforcer for relapse, and deserves greater attention in treatment and research.
      Clinical Trials registration NCT00679016.

PMID- 23146562
TI  - Cardiac lipofibromatosis.
AB  - We present a case of cardiac lipofibromatosis associated with atrial fibrillation
      and complete heart block requiring permanent pacemaker implantation.
      Multimodality cardiac imaging including transthoracic echocardiography and
      cardiac magnetic resonance were useful for tissue characterization of this rare
      cardiac diagnosis.

PMID- 23146561
TI  - A phenyl-thiadiazolylidene-amine derivative ejects zinc from retroviral
      nucleocapsid zinc fingers and inactivates HIV virions.
AB  - BACKGROUND: Sexual acquisition of the human immunodeficiency virus (HIV) through
      mucosal transmission may be prevented by using topically applied agents that
      block HIV transmission from one individual to another. Therefore, virucidal
      agents that inactivate HIV virions may be used as a component in topical
      microbicides. RESULTS: Here, we have identified 2-methyl-3-phenyl-2H
      [1,2,4]thiadiazol-5-ylideneamine (WDO-217) as a low-molecular-weight molecule
      that inactivates HIV particles. Both HIV-1 and HIV-2 virions pretreated with this
      compound were unable to infect permissive cells. Moreover, WDO-217 was able to
      inhibit infections of a wide spectrum of wild-type and drug-resistant HIV-1,
      including clinical isolates, HIV-2 and SIV strains. Whereas the capture of virus
      by DC-SIGN was unaffected by the compound, it efficiently prevented the
      transmission of DC-SIGN-captured virus to CD4+ T-lymphocytes. Interestingly,
      exposure of virions to WDO-217 reduced the amount of virion-associated genomic
      RNA as measured by real-time RT-qPCR. Further mechanism-of-action studies
      demonstrated that WDO-217 efficiently ejects zinc from the zinc fingers of the
      retroviral nucleocapsid protein NCp7 and inhibits the cTAR destabilization
      properties of this protein. Importantly, WDO-217 was able to eject zinc from both
      zinc fingers, even when NCp7 was bound to oligonucleotides, while no covalent
      interaction between NCp7 and WDO-217 could be observed. CONCLUSION: This compound
      is a new lead structure that can be used for the development of a new series of
      NCp7 zinc ejectors as candidate topical microbicide agents.

PMID- 23146563
TI  - The fluoroscopic swinging heart: a rare sight for the modern interventionalist.
AB  - Herein, we present the case of a 49-year-old woman who presented to a peripheral
      hospital with a 4-day history of progressive shortness of breath. Following a
      clinical diagnosis of heart failure and slightly elevated cardiac troponins on
      initial blood work, the patient was referred for same-day diagnostic coronary
      angiography, which revealed normal coronary arteries but the surprising finding
      of a fluoroscopic swinging heart due to a massive pericardial effusion. The
      patient promptly improved after emergent pericardiocentesis. Fluoroscopic clues
      to the diagnosis of pericardial effusion are reviewed, with accompanying
      illustrative video and hemodynamic tracings.

PMID- 23146564
TI  - Wolbachia strain wPip yields a pattern of cytoplasmic incompatibility enhancing a
      Wolbachia-based suppression strategy against the disease vector Aedes albopictus.
AB  - BACKGROUND: Cytoplasmic incompatibility (CI) is induced in nature by Wolbachia
      bacteria, resulting in conditional male sterility. Previous research demonstrated
      that the two Wolbachia strains (wAlbA and wAlbB) that naturally co-infect the
      disease vector mosquito Aedes albopictus (Asian tiger mosquito) can be replaced
      with the wPip Wolbachia strain from Culex pipiens. Since Wolbachia-based vector
      control strategies depend upon the strength and consistency of CI, a greater
      understanding is needed on the CI relationships between wPip, wAlbA and wAlbB
      Wolbachia in Ae. albopictus. METHODS: This work consisted of a collaborative
      series of crosses carried out in Italy and in US to study the CI relationships
      between the "wPip" infected Ae. albopictus strain (ARwP) and the superinfected SR
      strain. The Ae. albopictus strains used in Italian tests are the wPip infected
      ARwP strain (ARwPIT), the superinfected SR strain and the aposymbiotic AR strain.
      To understand the observed pattern of CI, crossing experiments carried out in USA
      focused on the study of the CI relationships between ARwP (ARwPUS) and
      artificially-generated single infected lines, in specific HTA and HTB, harbouring
      only wAlbA and wAlbB Wolbachia respectively. RESULTS: The paper reports an
      unusual pattern of CI observed in crossing experiments between ARwP and SR lines.
      Specifically, ARwP males are able to induce full sterility in wild type females
      throughout most of their lifetime, while crosses between SR males and ARwP
      females become partially fertile with male aging. We demonstrated that the
      observed decrease in CI penetrance with SR male age, is related to the previously
      described decrease in Wolbachia density, in particular of the wAlbA strain,
      occurring in aged superinfected males. CONCLUSIONS: The results here reported
      support the use of the ARwP Ae. albopictus line as source of "ready-made sterile
      males", as an alternative to gamma radiation sterilized males, for autocidal
      suppression strategies against the Asian tiger mosquito. In addition, the age
      dependent CI weakening observed in the crosses between SR males and ARwP females
      simplifies the downstream efforts to preserve the genetic variability within the
      laboratory ARwP colonies, to date based on the antibiotic treatment of wild
      captured superinfected mosquitoes, also reducing the costs.

PMID- 23146565
TI  - Changes in body weight and tuberculosis treatment outcome in Viet Nam.
AB  - SETTING: National Tuberculosis Programme, Viet Nam, 2008. OBJECTIVE: To assess
      the relationship between changes in body weight and tuberculosis (TB) treatment
      outcome. METHODS: All treatment cards of patients from a sample of 30 randomly
      selected treatment units in the country  were analysed. RESULTS: Of 2609
      patients, 2506 (96.1%) had a successful treatment outcome. The median body weight
      of all patients at diagnosis was 46.0 kg (25th and 75th percentiles 41-51). New
      sputum smear-positive TB patients with a successful treatment outcome gained an
      average  of 2.6 kg during treatment. Patients with weight loss during the first 2
      months of treatment were more likely to have an unsuccessful outcome than
      patients without (OR 4.9, 95%CI 3.0-7.9). Patients weighing <40 kg at treatment
      start who gained more than 5% of their body weight after  2 months of treatment
      had a significantly smaller risk of an unsuccessful treatment outcome than
      patients who did not (OR 0.2, 95%CI 0.05-0.96). CONCLUSIONS: Patients failing to
      gain weight or losing weight, particularly during the first 2 months of
      treatment, require particular attention,  as they appear to be at an increased
      risk of unsuccessful treatment outcome.

PMID- 23146566
TI  - Polarity and cell fate asymmetry in Caulobacter crescentus.
AB  - The production of asymmetric daughter cells is a hallmark of metazoan development
      and critical to the life cycle of many microbes, including the alpha
      proteobacterium Caulobacter crescentus. For Caulobacter, every cell division is
      asymmetric, yielding daughter cells with different morphologies and replicative
      potentials. This asymmetry in daughter cell fate is governed by the response
      regulator CtrA, a transcription factor that can also bind and silence the origin
      of replication. CtrA activity is controlled by a complex regulatory circuit that
      includes several polarly localized histidine kinases. This circuit ensures
      differential activation of CtrA in daughter cells, leading to their asymmetric
      replicative potentials. Here, we review progress in elucidating the molecular
      mechanisms regulating CtrA and the role of cellular polarity in this process.

PMID- 23146567
TI  - Clinical management of small-cell carcinoma of the urinary tract: a 10-year
      single-center's experience.
AB  - BACKGROUND: Small-cell carcinoma (SCC) comprises 1% of primary bladder tumors and
      approximately 2% of prostate neoplasms. Metastatic disease at diagnosis is
      common, and survival outcomes are extremely poor. There is controversy about the
      ideal clinical management of these patients. The neuron-specific enolase (NSE)
      serum levels have never been studied in patients with small-cell carcinoma of the
      urinary tract (SCCUT). PATIENTS AND METHODS: We report the clinical outcome of 12
      consecutive SCCUT patients treated during the past 10 years. We also study the
      NSE levels at diagnosis and during treatment. RESULTS: Patients with limited
      disease (LD) experienced a non-significant longer progression-free survival (PFS)
      and overall survival (OS) compared with extensive disease (ED) subjects. Patients
      with bladder SCC showed a significantly higher median PFS compared with prostate
      SCCUT patients (22 vs. 6 months; P = .034), although that difference did not
      impact on a significant longer OS. NSE levels decreased during chemotherapy
      administration in all patients with ED and baseline high levels. CONCLUSIONS: Our
      patients showed a poor prognosis as described in previous studies. A better
      outcome for patients with bladder SCC compared with prostate SCC could be
      suggested. Serum NSE levels should be further evaluated to prove its potential
      use in early diagnosis and treatment monitoring during chemotherapy.

PMID- 23146568
TI  - Short chain fatty acids and their receptors: new metabolic targets.
AB  - Fatty acids are carboxylic acids with aliphatic tails of different lengths, where
      short chain fatty acids (SCFAs) typically refer to carboxylic acids with
      aliphatic tails less than 6 carbons. In humans, SCFAs are derived in large part
      from fermentation of carbohydrates and proteins in the colon. By this process,
      the host is able to salvage energy from foods that cannot be processed normally
      in the upper parts of the gastrointestinal tract. In humans, SCFAs are a minor
      nutrient source, especially for people on Western diets. Intriguingly, recent
      studies, as highlighted here, have described multiple beneficial roles of SCFAs
      in the regulation of metabolism. Further interest in SCFAs has emerged due to the
      association of gut flora composition with obesity and other metabolic states. The
      recent identification of receptors specifically activated by SCFAs has further
      increased interest in this area. These receptors, free fatty acid receptor-2 and 
      3 (FFAR2 and FFAR3), are expressed not only in the gut epithelium where SCFAs are
      produced, but also at multiple other sites considered to be metabolically
      important, such as adipose tissue and pancreatic islets. Because of these
      relatively recent findings, studies examining the role of these receptors, FFAR2
      and FFAR3, and their ligands, SCFAs, in metabolism are emerging. This review
      provides a critical analysis of SCFAs, their recently identified receptors, and
      their connection to metabolism.

PMID- 23146569
TI  - Resveratrol administration or SIRT1 overexpression does not increase LXR
      signaling and macrophage-to-feces reverse cholesterol transport in vivo.
AB  - The natural polyphenol resveratrol has cardiometabolic protective properties.
      Resveratrol has been reported to be an activator of NAD+-dependent deacetylase
      sirtuin 1 (SIRT1), which may regulate liver X receptor (LXR) activity, thereby
      upregulating the expression of genes crucial in reverse cholesterol transport
      (RCT). In the present study, the effects of resveratrol and SIRT1 overexpression
      on RCT from macrophages-to-feces in vivo in C57BL/6 mice were determined.
      [3H]cholesterol-labeled mouse macrophages were injected intraperitoneally into
      mice treated with intragastric doses of the well-known LXR agonist T0901317,
      resveratrol, or a vehicle solution, and radioactivity was determined in plasma,
      liver, and feces. T0901317-treated mice presented increased [3H]cholesterol in
      plasma and HDL 48 h after the label injection. Treatment with T0901317 also
      increased liver ABCA1, G1, and G5 gene expression and reduced intestinal
      cholesterol absorption which were changes that were associated with a 2.8-fold
      increase in macrophage-derived [3H]cholesterol in feces. In contrast, resveratrol
      treatment had no effect on liver LXR signaling or fecal [3H]cholesterol
      excretion. A separate experiment was conducted in SIRT1 transgenic mice. Liver
      LXR-target gene expression and magnitude of macrophage-derived [3H]cholesterol in
      plasma, liver, and feces of SIRT1 transgenic mice did not differ from those of
      wild-type mice. We conclude that neither resveratrol administration nor SIRT1
      overexpression upregulate liver LXR-target genes and macrophage-to-feces RCT in
      vivo.

PMID- 23146570
TI  - Rare diagnosis of IgG4-related systemic disease by lip biopsy in an international
      Sjogren syndrome registry.
AB  - IgG4-related disease has been recently defined as a distinct clinic-pathologic
      entity, characterized by dense IgG-4 plasmacytic infiltration of diverse organs,
      fibrosis, and tumefactive lesions. Salivary and lacrimal glands are a target of
      this disease and, when affected, may clinically resemble Kuttner tumor, Mikulicz
      disease, or orbital inflammatory pseudotumor. In some patients, the disease is
      systemic, with metachronous involvement of multiple organs, including the
      pancreas, aorta, kidneys, and biliary tract. We report a 66-year-old man who
      presented with salivary gland enlargement and severe salivary hypofunction and
      was diagnosed with IgG4-related disease on the basis of a labial salivary gland
      biopsy. Additional features of his illness included a marked peripheral
      eosinophilia, obstructive pulmonary disease, and lymphoplasmacytic aortitis. He
      was evaluated in the context of a research registry for Sjogren syndrome and was
      the only 1 of 2594 registrants with minor salivary gland histopathologic findings
      supportive of this diagnosis.

PMID- 23146571
TI  - A comparative study of closed versus open reduction and internal fixation (using
      retromandibular approach) in the management of subcondylar fracture.
AB  - OBJECTIVE: The aim of this study was to evaluate the clinical and radiologic
      outcomes of open reduction and internal fixation compared with closed reduction
      approach for fractures occurring at the subcondylar level. STUDY DESIGN: Twenty
      two patients with subcondylar fractures were included in the study; 12 patients
      were treated by closed reduction and 10 patients underent open reduction and
      rigid internal fixation, with follow-up at 3 and 6 months. Selection of patients
      for open and closed procedures was done on a random basis. RESULTS AND
      CONCLUSIONS: The results showed that open reduction and internal fixation of
      displaced subcondylar fractures showed better results clinically as well as
      radiographically compared with similar fractures treated by closed reduction.

PMID- 23146572
TI  - In vitro evaluation of cytotoxicity of hyaluronic acid as an extracellular matrix
      on OFCOL II cells by the MTT assay.
AB  - OBJECTIVE: To evaluate the cytotoxicity of hyaluronic acid (HA) on a tissue
      engineered compound for bone grafting containing osteoblastic cells (OFCOL II),
      platelet-rich plasma (PRP) with or without thrombin (Thr), and hydroxyapatite
      (HP) by the MTT assay. STUDY DESIGN: Studied groups were formed as follows: (A)
      Cells + HA + PRP with Thr + hydroxyapatite (HP); (B) Cells + HA + PRP + HP; (C)
      Cells + HA + HP; (D) Cells + HP; (E) Cells + HA; (F) Cells + PRP with Thr; (G)
      Cells + PRP; and (H) Pure Dulbecco's modified Eagle's medium (DMEM) with 15%
      fetal bovine serum. A 2-way ANOVA and Tukey's test were applied for statistical
      analysis (P < .05). RESULTS: Results of cell viability for each group were as
      follows: A: 79%, B: 67%, C: 68%, D: 99%, E: 74%, G: 89%, F: 90%, and Group H:
      100%. CONCLUSIONS: Results suggested a decrease in cell viability in the presence
      of HA.

PMID- 23146573
TI  - Skeletal muscle satellite cell activation following cutaneous burn in rats.
AB  - BACKGROUND: Cutaneous burn distant from skeletal muscles induces atrophy;
      however, its effect on muscle stem cells resident in skeletal muscle (satellite
      cells) distal to burn is not known. METHODS: Satellite cell activation was
      measured in predominantly fast-twitch [tibialis anterior, extensor digitorum
      longus (EDL), plantaris, and gastrocnemius] and slow-twitch (soleus) muscles of
      rats that received either 40% total body surface area full-thickness scald burn
      or sham burn to the trunk area by determining bromodeoxyuridine incorporation,
      MyoD, and Pax7 immunohistochemistry in vivo <=48 h after burn. To determine the
      effects of circulating factors on satellite cell activation, satellite cell
      cultures were treated with serum from sham or burn rats. RESULTS: In vivo
      activation of satellite cells was increased in fast muscles isolated from burn as
      compared to sham animals, whereas a significant response was not seen in slow
      muscles. Serum taken from animals in the burn group increased the activation of
      satellite cells isolated from both sham and burn animals in vitro, suggesting
      that circulating factors have the potential to increase satellite cell activation
      following burn. CONCLUSIONS: Increases in satellite cell activation in muscles
      distal to burn are fiber-type-dependent, and circulating factors may play a role
      in the activation of satellite cells following burn. A better understanding of
      the impact of burn on satellite cell functionality will allow us to identify the
      cellular mechanisms of long-term muscle atrophy.

PMID- 23146574
TI  - Assessment of mortality prediction models in a Ghanaian burn population.
AB  - PURPOSE: Over 40 new or modified outcome prediction models have been developed
      for severe burns; with age, total burned surface area (TBSA) and inhalation area
      as major determinants of mortality. The objective of this study was to assess
      their applicability in a developing country. PROCEDURES: Data were collected
      retrospectively of a consecutive series of 261 patients (2009-2011) admitted to a
      Burns Intensive Care. Five outcome prediction models based on admission criteria
      were evaluated: Bull grid, Abbreviated Burn Severity Index--ABSI, Ryan-model,
      Belgian Outcome in Burn Injury--BOBI and revised Baux. Discriminative power and
      goodness-of-fit were assessed by receiver operating characteristic analyses (area
      under the curve--AUC) and Hosmer-Lemeshow tests. FINDINGS: Median age was 10.5
      years (IQR: 2.5-27 years), median TBSA 21% (IQR: 11-34%); 55.2% were male, 28
      patients died (10.7%). Only 2 patients were intubated (0.8%). The AUC were
      between 77 and 86%. The ABSI model showed the best calibration (28.7 expected
      deaths). Ryan, BOBI and rBaux significantly underestimated mortality, whereas
      Bull showed an overestimation. CONCLUSION: This study on a young group of burn
      patients showed moderate to good discriminative power using all five prediction
      models. The expected number of deaths tended to be underestimated in the three
      most recent prediction models.

PMID- 23146575
TI  - Early single-shot intravenous steroids do not affect pulmonary complications and
      mortality in burned or scalded patients.
AB  - BACKGROUND AND OBJECTIVES: Inhalation injury, especially in combination with
      cutaneous burns, is the major cause of morbidity and mortality in patients
      admitted to burn care centers. Either with or without the presence of a cutaneous
      burn, inhalation injury contributes to high risk for developing severe pulmonary
      complications. Steroids may reduce a prolonged and destructive inflammatory
      response to toxic or allergic substances. The objective of this study was to
      evaluate the effect of early single-shot intravenous steroids on pulmonary
      complications and mortality in burned or scalded patients with or without
      inhalation injury. METHODS: Retrospective analysis of a prospective single center
      database of patients registered between 1989 and 2011 who were admitted to the
      intensive care unit of our burn care center after burn or scald injury. Uni
      variate statistical analysis was performed comparing two groups (steroid treated
      vs. non steroid treated patients) with regard to clinical outcome. Main
      parameters were sepsis, mortality and pulmonary complications such as pneumonia,
      ALI and ARDS. Multi-variate analysis was used by logistic regression with
      mortality and pulmonary complications as the dependent variables to identify
      independent risk factors after burn or scald injuries. RESULTS: A total of 1637
      patients with complete data were included in the present analysis. 199 (12.2%)
      received single-shot intravenous steroids during the prehospital phase of care.
      In 133 (66.8%) of these patients, inhalation injury was diagnosed via
      bronchoscopy. Steroid treated patients had sustained a significantly higher
      severity of burn than non-steroid treated patients (Abbreviated Burn Severity
      Index 7.1+/-3 vs. 6.0+/-2.9; p<0.001). In a multivariate analysis using a
      logistic regression model early intravenous steroid treatment had no significant
      effect on pulmonary complications and mortality. CONCLUSIONS: In our single
      center cohort of burned and scalded patients single-shot intravenous steroids
      during the pre-hospital phase of care was not associated with pulmonary
      complications or mortality.

PMID- 23146576
TI  - Assessment of atrial electromechanical delay in children with acute rheumatic
      fever.
AB  - PURPOSE: There may be an increase in the risk of atrial arrhythmia due to left
      atrial enlargement and the influence on conduction system in acute rheumatic
      fever. The aim of this study is to investigate atrial electromechanical delay and
      P-wave dispersion in patients with acute rheumatic fever. PATIENTS: A total of 48
      patients diagnosed with acute rheumatic fever and 40 volunteers of similar age,
      sex, and body mass index were included in the study. The study groups were
      compared for M-mode echocardiographic parameters, interatrial electromechanical
      delay, intra-atrial electromechanical delay, and P-wave dispersion. RESULTS:
      Maximum P-wave duration, P-wave dispersion, and interatrial electromechanical
      delay were significantly higher in patients with acute rheumatic fever compared
      with the control group (p < 0.001). However, there was no difference in terms of
      intra-atrial electromechanical delay (p > 0.05). For patients with acute
      rheumatic fever, a positive correlation was identified between the left atrium
      diameter and the P-wave dispersion and interatrial electromechanical delay (r =
      0.524 and p < 0.001, and r = 0.351 and p = 0.014, respectively). Furthermore, an
      important correlation was also identified between the P-wave dispersion and the
      interatrial electromechanical delay (r = 0.494 and p < 0.001). CONCLUSION: This
      study shows the prolongation of P-wave dispersion and interatrial
      electromechanical delay in acute rheumatic fever. Left atrial enlargement can be
      one of the underlying reasons for the increase in P-wave dispersion and
      interatrial electromechanical delay.

PMID- 23146577
TI  - Population genetic analysis and sub-structuring of Theileria parva in the
      northern and eastern parts of Zambia.
AB  - BACKGROUND: Theileriosis, caused by Theileria parva, is an economically important
      disease in Africa. It is a major constraint to the development of the livestock
      industry in some parts of eastern, central and southern Africa. In Zambia,
      theileriosis causes losses of up to 10,000 cattle annually. METHODS: Cattle blood
      samples were collected for genetic analysis of Theileria parva from Isoka and
      Petauke districts in Zambia. Microsatellite analysis was then performed on all
      Theileria parva positive samples for PCR using a panel of 9 microsatellite
      markers. Microsatellite data was analyzed using microsatellite toolkit, GenAlEx
      ver. 6, Fstat ver. 2.9.3.2, and LIAN computer softwares. RESULTS: The combined
      percentage of positive samples in both districts determined by PCR using the p104
      gene primers was 54.9% (95% CI: 46.7 - 63.1%, 78/142), while in each district, it
      was 44.8% (95% CI: 34.8 - 54.8%) and 76.1% (95% CI = 63.9 - 88.4%) for Isoka and
      Petauke districts, respectively. We analyzed the population genetic structure of
      Theileria parva from a total of 61 samples (33 from Isoka and 28 from Petauke)
      using a panel of 9 microsatellite markers encompassing the 4 chromosomes of
      Theileria parva. Wright's F index (FST = 0.178) showed significant
      differentiation between the Isoka and Petauke populations. Linkage disequilibrium
      was observed when populations from both districts were treated as a single
      population. When analyzed separately, linkage disequilibrium was observed in
      Kanyelele and Kalembe areas in Isoka district, Isoka district overall and in
      Petauke district. Petauke district had a higher multiplicity of infection than
      Isoka district. CONCLUSION: Population genetic analyses of Theileria parva from
      Isoka and Petauke districts showed a low level of genotype exchange between the
      districts, but a high level of genetic diversity within each district population,
      implying genetic and geographic sub-structuring between the districts. The sub
      structuring observed, along with the lack of panmixia in the populations, could
      have been due to low transmission levels at the time of sampling. However, the
      Isoka population was less diverse than the Petauke population.

PMID- 23146578
TI  - Accommodating climate change contingencies in conservation strategy.
AB  - Species ranges are seldom at equilibrium with climate, because several
      interacting factors determine distribution, including demographic processes,
      dispersal, land use, disturbance (e.g., fire), and biotic interactions.
      Conservation strategies in a changing climate therefore cannot be based only on
      predicted climate-driven range shifts. Here, we explore conservation and
      management options in a framework for prioritizing landscapes based on two 'axes
      of concern': landscape conservation capacity attributes (percentage of protected
      area, connectivity, and condition of the matrix) and vulnerability to climate
      change (climate change velocity and topographic variation). Nine other
      conservation actions are also presented, from understanding and predicting to
      planning and managing for climate change. We emphasize the need for adaptation
      and resilience in populations, ecosystems, and the conservation environment
      itself.

PMID- 23146579
TI  - Is publication rate an equal opportunity metric?
AB  - Publication quantity is frequently used as a ranking metric for employment,
      promotion, and grant success, and is considered an unbiased metric for comparing
      applicants. However, research suggests that women publish fewer papers, such that
      the measure may not be equitable. We suggest reasons for the disparity, and
      potential future remedies. Publication quality and impact provide more equitable
      metrics of research performance and should be stressed above publication
      quantity.

PMID- 23146581
TI  - The urgent need for ethical guidelines to protect children in the dissemination
      of research findings.

PMID- 23146580
TI  - Childhood maltreatment and conduct disorder: independent predictors of criminal
      outcomes in ADHD youth.
AB  - OBJECTIVE: Children with attention-deficit/hyperactivity disorder (ADHD) are at
      heightened risk for maltreatment in childhood and criminality as they enter into
      adolescence and early adulthood. Here, we investigated the effect of moderate to
      severe childhood maltreatment on later criminality among adolescents/young adults
      diagnosed with ADHD in childhood while accounting for the contributions of other
      known risk factors such as early conduct disorder (CD). METHODS: Eighty-eight
      participants from a longitudinal study of children diagnosed with ADHD and
      screened for comorbid disorders at age 7-11 years were assessed for maltreatment
      histories at the time of the 10-year adolescent follow-up. Detailed juvenile and
      adult criminal records were obtained from the New York State Division of Criminal
      Justice Services approximately 3-years after commencement of the follow-up study.
      We used regression analyses to determine predictors of adolescent/young adult
      criminal behavior. RESULTS: Moderate to severe childhood maltreatment increased
      the risk of adolescent/young adult arrest over and above the risk associated with
      childhood CD, while both childhood maltreatment and childhood CD significantly
      increased the risk of recidivism. ADHD youth classified as maltreated were three
      and a half times more likely to be arrested when compared to ADHD youth without a
      maltreatment classification. CONCLUSION: We established maltreatment as a risk
      factor for criminality in ADHD youth and demonstrated that this relationship was
      independent of the contributions of CD, and established risk factor for
      antisocial behavior in this population. The findings highlight the need for
      maltreatment screening in children with ADHD in order to identify those at
      heightened risk for criminal activity, and target treatment to improve outcome in
      this high-risk group of children.

PMID- 23146582
TI  - Revision total knee arthroplasty using a constrained condylar knee prosthesis in
      conjunction with a posterior stabilized articular polyethylene.
AB  - Legacy constrained condylar knee (LCCK) components are designed in the way that
      they can also be used in conjunction with a posterior-stabilized (PS)
      polyethylene insert, when adequate collateral stability is present. This study
      comprised 27 revision total knee arthroplasties (TKA) treated using an LCCK
      prosthesis and a PS polyethylene insert. Substantial range of motion and Knee
      Society score improvements were achieved in all subjects. Radiolucent lines
      between the block-cement were noted in 6 of 27 knees, but not significant. During
      TKA requiring the use of a femoral augment or stem extension, the design offering
      least constraint can be chosen, and an LCCK prosthesis with a PS polyethylene
      insert could be a satisfactory option.

PMID- 23146583
TI  - Highly cross-linked polyethylene in total hip arthroplasty for osteonecrosis of
      the femoral head: a minimum 5-year follow-up study.
AB  - We evaluated 162 hips with osteonecrosis of the femoral head that had undergone
      THA using highly cross-linked polyethylene liner after a minimum follow-up of 5
      years. Neither femoral nor acetabular components displayed radiographic evidence
      of mechanical loosening or osteolysis, and no components had been revised at the
      latest follow-up. The mean rate of linear liner wear was 0.038 mm/year.
      Univariate regression analysis did not demonstrate that age, gender, weight,
      activity level or cup inclination had any influence on penetration. While the
      long term effects of altered mechanical properties of highly cross-linked PE
      remain unknown, the clinical and radiographic results at a minimum of 5 years are
      promising for this high-risk population.

PMID- 23146584
TI  - Failure of the rotating-hinge knee megaprosthesis.
AB  - Recently, rotating hinge knee prostheses were applied more frequently due to
      improving modern implant designs. They are predominantly used in specific
      conditions with major bone defect or insufficiency of the collateral ligaments
      around the knee, often as salvage procedures. A case of rotating hinge knee
      megaprosthesis failure due to isolated tibial polyethylene stopper broken, which
      was never reported before, was investigated and treated in our institution. We
      suggested that rotating hinge knee prosthesis with incompetent medial collateral
      ligament is apt to failure due to the high valgus moment during gait. Sacrificing
      lateral collateral ligament or cutting the femur in slightly less than the normal
      5 degrees  to 7 degrees  valgus may eliminate the risk of complication.

PMID- 23146585
TI  - Cement-in-cement revision for selected Vancouver Type B1 femoral periprosthetic
      fractures: a biomechanical analysis.
AB  - The aim of this study was to perform a biomechanical analysis of the cement-in
      cement (c-in-c) technique for fixation of selected Vancouver Type B1 femoral
      periprosthetic fractures and to assess the degree of cement interposition at the
      fracture site. Six embalmed cadaveric femora were implanted with a cemented
      femoral stem. Vancouver Type B1 fractures were created by applying a combined
      axial and rotational load to failure. The femora were repaired using the c-in-c
      technique and reloaded to failure. The mean primary fracture torque was 117 Nm
      (SD 16.6, range 89-133). The mean revision fracture torque was 50 Nm (SD 16.6,
      range 29-74), which is above the torque previously observed for activities of
      daily living. Cement interposition at the fracture site was found to be minimal.

PMID- 23146586
TI  - Accuracy and clinical utility of a peri-operative risk calculator for total knee
      arthroplasty.
AB  - Utilizing the Medicare Provider Analysis and Review dataset, a, peri-operative
      total knee arthroplasty (TKA) risk calculator was created based on select
      preoperative comorbidities. We retrospectively identified and reviewed 2284
      primary TKAs at a single institution from 2000-2008. A numerical, predicted
      complication risk was established for each patient. Actual complications
      occurring within the first 14 post-operative days were recorded. Statistical
      analysis was performed using the C-statistic and ANOVA test. Patients with higher
      predicted probability of a complication did show higher complication rates. The
      corresponding C-statistic was 0.609. (95% Confidence Interval: 0.542-0.677). When
      the patients were divided into 4 groups based on their calculated complication
      risk (0-5%, 5-10%, 10-25%, >25%) the statistical significance of the associated
      ANOVA was P < .001, showing that patients with higher predicted risk experienced
      more complications, and those with lower predicted risk experienced fewer
      complications. Based on our results, the calculator has predictive value and is
      clinically relevant.

PMID- 23146587
TI  - Experimental determination of organelle targeting-peptide cleavage sites using
      transient expression of green fluorescent protein translational fusions.
AB  - The majority of nuclear-encoded organellar proteins contain a cleavable
      presequence, which is necessary for protein targeting and import into the correct
      cellular compartment. Knowledge about targeting-peptide cleavage sites is
      essential for the structural and functional characterization of the mature
      organellar proteins as well as for a deeper understanding of the import process.
      Because of the low consensus and high variability of presequences, bioinformatics
      of targeting-peptide cleavage fails to predict the length of the targeting
      peptide with high confidence. Therefore, we have developed a rapid and robust
      method to experimentally determine the cleavage site of the transit peptide for
      proteins imported into mitochondria or plastids. The protein precursor with green
      fluorescent protein (GFP) fused to its C-terminus is transiently expressed in
      cells (for animal proteins) or protoplasts (for plant proteins), allowing
      translocation into organelles and removal of the transit peptide. After lysis,
      the matured protein is immunopurified using an anti-GFP antibody coupled to
      magnetic beads. The N-terminal amino sequence is then determined by Edman
      microsequencing or mass spectrometry. The method has been validated using
      proteins with known targeting-peptide sequences and is suitable for animal and
      plant organelle-targeted proteins.

PMID- 23146588
TI  - Single-step cloning of a hybridoma producing a monoclonal antibody against a
      target protein.
AB  - We have developed a simple and time-saving method to identify hybridoma clones
      producing an antibody against a target protein among a large number of hybridomas
      in a single step. This method is very useful as the primary screening tool for
      hybridomas producing monoclonal antibodies if several micrograms of the target
      protein is available.

PMID- 23146589
TI  - A fluorogenic phospholipid for the detection of lysosomal phospholipase A2
      activity.
AB  - Lysosomal phospholipase A2 (group XV PLA2, LPLA2) is a lysosomal enzyme linked to
      drug-induced phospholipidosis. We developed phospholipid "smart probes" based on
      the conversion of a quenched fluorogenic substrate to a fluorescent product. Due
      to the preference of LPLA2 for phosphatidylglycerol, three fluorogenic
      phosphatidylglycerols were synthesized. Two fluorogenic phosphatidylglycerols
      were conjugated with one FAM (fluorescein amidite) group and one DABCYL [4-(4
      dimethylaminophenylazo)-benzoyl] group; the third substrate consisted of two FAM
      groups conjugated at the sn-1 and sn-2 positions. The sn-1 ester linkage was
      replaced with an amide linkage. 1-FAM-2-DABCYL-PG was degraded by recombinant
      LPLA2 and mouse serum but not by the serum obtained from LPLA2-deficient mice
      when 1,2-dioleoyl-PG/1-FAM-2-DABCYL-PG liposomes were used. The formation of 1
      FAM-lyso-PG generated from 1-FAM-2-DABCYL-PG in the presence of LPLA2 was
      quantitatively determined by fluorescent measurements. The 1-FAM-2-DABCYL-PG
      incorporated into 1,2-dioleoyl-phosphatidylcholine/sulfatide liposomes was used
      to evaluate the effect of the cationic amphiphilic drugs amiodarone and
      fluoxetine on LPLA2 activity. The IC(50) values of amiodarone and fluoxetine
      estimated by fluorescent measurement were 10 and 19MUM, respectively. These
      results indicate that 1-FAM-2-DABCYL-PG is a specific substrate for LPLA2 and a
      useful reagent for the detection of LPLA2 activity from multiple sources.

PMID- 23146590
TI  - Flow cytometry-based ultra-high-throughput screening assay for cellulase
      activity.
AB  - We have developed a novel, ultra-high-throughput screening assay for the
      detection of cellulase activity based on fluorescence-activated cell sorting
      (FACS) and double emulsion technology. Cellulase activity is detected using a
      series of coupled enzymes, including hexose oxidase (HOx), which generates
      hydrogen peroxide from the reducing sugars released by cellulases in the presence
      of any natural or artificial substrate. The assay can be adapted to suit a
      microtiter plate format, but the highest throughput is achieved by using FACS to
      screen high-complexity cellulase clone libraries. Using this approach, we
      achieved a 12-fold enrichment of positive (cellulase-expressing) cells in
      cellulase reference libraries after just one sorting round.

PMID- 23146591
TI  - Quinalphos induced oxidative stress and histoarcheitectural alterations in adult
      male albino rats.
AB  - Quinalphos is a synthetic organophosphate used as a broad spectrum insecticide
      and acaricide. The present study investigates the effect of three sub-lethal
      doses (0.52, 1.04, 2.6 mg/kg b.wt) of quinalphos for variable durations (15, 30
      and 90 days) on oxidative stress and histopathological changes in adult male
      rats. Quinalphos treatment for 15 and 30 days resulted in a dose dependent
      significant increase in malondialdehyde (MDA) levels and glutathione-S
      transferase (GST) activity together with a concurrent decrease in ferric reducing
      ability of plasma (FRAP) and glutathione (GSH) content. Quinalphos treatment for
      90 days also induced a significant increase in MDA levels and GST activity but
      the effect was not dose-dependent. Histopathological examination of liver
      revealed architectural disarray and dilatation of sinusoids, focal fatty changes,
      accumulation of eosinophils and single cell necrosis with increasing doses.
      However, spleen and kidney did not show any histological changes. Administration
      of quinalphos resulted in oxidative stress and free radical induced injury as
      evidenced by increased lipid peroxidation, decreased FRAP and histopathological
      changes in liver.

PMID- 23146592
TI  - Nitric oxide mediated effects on reproductive toxicity caused by carbon disulfide
      in male rats.
AB  - This study investigated nitric oxide (NO) mediation of carbon disulfide (CS(2))
      toxicity that compromised male rat spermatogenesis and endocrine function. Rats
      were exposed to multiple levels of CS(2) concentration (0, 50, 250, 1250
      mg/m(3)). A 1250 mg/m(3) CS(2)+sodium nitroprusside (SNP) group and a 1250
      mg/m(3) CS(2)+NG-monomethyl-L-arginine (L-NMMA) group were established to explore
      the role of NO in mediating CS(2) toxicity. NO concentrations, NO synthase (NOS)
      activity, and sex hormone levels were measured, and sperm characteristics were
      observed and analyzed. Our data show that CS(2) exposure decreased: NOS activity;
      tissue NO concentrations; serum levels of gonadotropin-releasing hormones,
      luteinizing hormones, and testosterone; and sperm count and activity. In
      contrast, increased serum follicle-stimulating hormone concentrations and
      teratospermia were observed with CS(2) exposure. SNP reduced some of the toxic
      effects of CS(2), while L-NMMA treatment showed no effect. The results suggests
      that NO mediates compromised reproductive system function caused by CS(2)
      exposure.

PMID- 23146594
TI  - The influence of habitus in the relationship between cultural capital and
      academic achievement.
AB  - Scholars routinely use cultural capital theory in an effort to explain class
      differences in academic success but often overlook the key concept of habitus.
      Rich, longstanding debates within the literature suggest the need for a closer
      examination of the individual effects of cultural capital and habitus. Drawing
      upon the writings of Pierre Bourdieu, I use a longitudinal dataset to examine the
      effects of multiple operationalizations of cultural capital on academic
      achievement and the mediating effects of habitus. Using first difference models
      to control for time-invariant unobserved characteristics, I find that typical
      operationalizations of cultural capital (i.e. high-arts participation and reading
      habits) have positive effects on GPA that are completely mediated through
      habitus. These results stress the importance of habitus in the relationship
      between cultural capital and academic achievement for disadvantaged youth.

PMID- 23146593
TI  - Hydroxypropyl methylcellulose, a viscous soluble fiber, reduces insulin
      resistance and decreases fatty liver in Zucker Diabetic Fatty rats.
AB  - BACKGROUND: Diets producing a high glycemic response result in exaggerated
      insulin secretion which induces hepatic lipogenesis, contributing to development
      of insulin resistance and fatty liver. Viscous dietary fibers blunt the
      postprandial rise in blood glucose, however their effect on type 2 diabetes and
      obesity are not entirely known. This study examined the effect of chronic
      consumption of the viscous, non-fermentable dietary fiber, hydroxypropyl
      methylcellulose (HPMC), on glucose control, insulin resistance and liver lipids
      in an obese diabetic rat model. METHODS: Three groups of Zucker Diabetic Fatty
      (ZDF) rats were fed diets containing either 5% non-viscous cellulose (control),
      low viscosity HPMC (LV-HPMC) or high viscosity HPMC (HV- HPMC) for six weeks.
      Zucker lean littermates consuming cellulose served as a negative control. Markers
      of glucose control, including oral glucose tolerance test, glycated hemoglobin
      and urinary glucose, were measured as well as adiposity and the accumulation of
      liver lipids. RESULTS: The HPMC diets increased the viscosity of the small
      intestinal contents and reduced the postprandial rise in blood glucose. The food
      efficiency ratio was greater with HPMC feeding compared to the obese control and
      urinary excretion of glucose and ketone bodies was reduced. The two HPMC groups
      had lower glycated hemoglobin and kidney weights and a reduced area under the
      curve during a glucose tolerance test, indicating improved glucose control.
      Epididymal fat pad weight as percent of body weight was reduced in the HV-HPMC
      group compared to the obese control group. The HV-HPMC group also had lower
      concentrations of liver lipid and cholesterol and reduced liver weight. However,
      HV-HPMC feeding did not affect hepatic gene expression of SREBP-1c or FAS. Muscle
      concentration of acylcarnitines, a lipid intermediate in fatty acid beta
      oxidation, was not different between the HPMC groups and obese control,
      suggesting no change in muscle fatty acid oxidation by HPMC. CONCLUSIONS:
      Consumption of the viscous non-fermentable fiber HPMC decreased diabetic wasting,
      improved glucose control and reduced insulin resistance and fatty liver in a
      model of obesity with diabetes.

PMID- 23146595
TI  - Does misery love company? Civic engagement in economic hard times.
AB  - We examine how economic hardship affects civic engagement. Using the Roper
      Political and Social Trends data, we show that the unemployed were less civically
      engaged throughout the period covered in the data (1973-1994). The gap in civic
      engagement between the employed and the unemployed is stable throughout the
      period. We find little evidence that national economic recession affects the
      overall level of civic engagement. We do find that higher state unemployment is
      positively related to political participation for both employed and unemployed
      residents, especially for political partisans. Finally, we find a strong and
      negative relationship between state-level income inequality and civic engagement.
      Our findings suggest that in terms of civic engagement: (1) the state-level
      economic context matters more than the national context; (2) economic recession
      may affect political and non-political civic participation differently; (3)
      economic inequality, rather than economic hardship, appears more negatively to
      impact civic engagement.

PMID- 23146596
TI  - Bonding alone: Familism, religion, and secular civic participation.
AB  - This study examines the influence of familism, religion, and their interaction on
      participation in secular voluntary associations. We develop an insularity theory
      to explain how familism and religion encourage Americans to avoid secular civic
      participation. Using data from the first wave of the National Survey of Families
      and Households, this study finds that familism reduces participation in secular
      organizations. Moreover, religion moderates the effect of familism: specifically,
      religious involvement tends to increase the negative effect of familism on
      secular civic participation. Although religious involvement in and of itself
      fosters secular civic participation, strong familism tends to dampen positive
      impacts of religious involvement. For familistic individuals, religious
      congregations appear to reinforce their insularity within their immediate social
      circle and family.

PMID- 23146597
TI  - Diversity in action: Interpersonal networks and the distribution of advice.
AB  - Does diversity beget the active dissemination of social support in the form of
      advice to others? Previous research by Robert Putnam suggests that individuals in
      compositionally diverse geographical areas become closed off from their social
      ties and less trusting of others, which are both antithetical to social support
      exchange. We argue, however, that studies of compositional diversity are ill
      suited to reflect diversity as it is actually lived and experienced in social
      life. Drawing from the first nationally representative study with comprehensive
      indicators of interactional diversity in social life, we analyze self-reports of
      advice-giving across a variety of social roles. Results of regression analysis
      are consistent: greater interactional diversity is positively associated with
      advice-giving, whether the target is stranger, neighbor, close friend, or family
      member. These findings hold independent of important covariates such as
      reciprocity, sociability, and homophily. This research contributes to a growing
      literature set on identifying the unanticipated benefits of diversity in modern
      society. In sum, we call future research to consider not only diversity in
      structure, but also diversity in action.

PMID- 23146598
TI  - Determinants of marital quality in an arranged marriage society.
AB  - Drawing on a uniquely large number of items on marital quality, this study
      explores the determinants of marital quality in Chitwan Valley, Nepal. Marital
      quality is measured with five dimensions identified through exploratory factor
      analysis, comprising satisfaction, communication, togetherness, problems, and
      disagreements. Gender, education, spouse choice, and marital duration emerge as
      the most important determinants of these dimensions of marital quality.
      Specifically, men, those with more schooling, those who participated in the
      choice of their spouse, and those who have been married longer have higher levels
      of marital quality. By contrast, caste, occupation, age at marriage, and number
      of children have little to no association with marital quality. However, while we
      identify key determinants of marital quality in this context, the majority of
      variation in marital quality remains unexplained.

PMID- 23146599
TI  - Social origins, hukou conversion, and the wellbeing of urban residents in
      contemporary China.
AB  - This paper examines the determinants and consequences of rural to urban
      registration (hukou) mobility in contemporary China, focusing on the link between
      social origins, hukou conversion, and the consequences of conversion. In contrast
      to massive rural-urban migration, hukou conversion is difficult and rare, but
      childhood urban residence increases the likelihood of achieving an urban hukou.
      Compared to people with urban origins, hukou converters are more likely to enter
      tertiary institutions, but are significantly less likely to do so subsequent to
      hukou conversion. Individual converters from rural origins are more likely to
      work in non-manual occupations. Collective converters earn significantly less
      than people with urban origins. Individual converters with rural childhoods, who
      used to be at the bottom of the society, are significantly happier than other
      urban residents, although they are less healthy. These results show that the
      effect of hukou conversion varies across hukou converters from different social
      origins.

PMID- 23146600
TI  - Why are religious people happy? The effect of the social norm of religiosity
      across countries.
AB  - Drawing on social norms theories, we suggest that religiosity substantially
      increases subjective well-being if it is considered normative in a certain
      national context. In Study 1, we test this hypothesis using an indicator of a
      country's social norm of religiosity that includes both the national level of
      religiosity and the social desirability of religion. The results of a multilevel
      regression analysis suggest that religious individuals are on average happier and
      more satisfied with life than non-religious individuals. This effect is stronger
      in religious countries with dominant negative attitudes towards non-believers. In
      Study 2, we further examine whether the differences in social recognition of
      religious and non-religious individuals in countries where religiosity is
      normative account for this finding. The results of a moderated mediation analysis
      indicate that in religious countries, religious people report being treated with
      more respect, which partially explains their higher levels of happiness and life
      satisfaction.

PMID- 23146601
TI  - Measures of "Race" and the analysis of racial inequality in Brazil.
AB  - Quantitative analyses of racial disparities typically rely on a single
      categorical measure to operationalize race. We demonstrate the value of an
      approach that compares results obtained using various measures of race. Using a
      national probability sample of the Brazilian population that captured race in six
      formats, we first show how the racial composition of Brazil can shift from
      majority white to majority black depending on the classification scheme. In
      addition, using quantile regression, we find that racial disparities are most
      severe at the upper end of the income distribution; that racial disparities in
      earnings are larger when race is defined by interviewers rather than self
      identified; and that those classified as "black" suffer a greater wage penalty
      than those classified as "brown." Our findings extend prior conclusions about
      racial inequality in Brazil. More generally, our analysis demonstrates that
      comparison of results across measures represents a neglected source of analytic
      leverage for advancing empirical knowledge and theoretical understanding of how
      race, as a multidimensional social construct, contributes to the production of
      social inequality.

PMID- 23146602
TI  - Social Assistance dynamics in Sweden: Duration dependence and heterogeneity.
AB  - This article uses data on all persons who ever received Social Assistance (SA) in
      Sweden 1991-2007 (N=2,638,681 observations; 882,416 individuals) to study whether
      there is duration dependence in SA, i.e., whether the probability to remain in SA
      increases over the individual duration of SA recipiency. The risk of remaining in
      SA is higher at longer durations, but around half of this risk difference is
      caused by selection (those with favourable characteristics exit first, while
      those with higher likelihood of SA remain). This is captured by control variables
      and by conditioning on SA sequences as a method to control for unobserved
      heterogeneity. The probability to remain in SA increases with 2-5 percentage
      points per year during the first five calendar years, implying that duration
      dependence is substantively but not dramatically important: Nearly 8% stay in SA
      the fifth year after entry, but only 4% would do so in the absence of duration
      dependence.

PMID- 23146603
TI  - Linguistic isolation in the home and community: Protection or risk for young
      children?
AB  - Studies of immigrant adaptation in the United States emphasize the importance of
      duration of residence, language use, location of schooling and other factors
      related to the migration process in determining outcomes for immigrants. Research
      also points to the variability of socioeconomic mobility among immigrants and
      their descendants across receiving contexts encountered in the United States.
      This paper extends this model to young children and examines how the linguistic
      environment of the family and the community interact to produce differential
      developmental outcomes. The analyses rely on data from the Early Childhood
      Longitudinal Study-Birth Cohort (ECLS-B) and 2000 US Census. Children's cognitive
      scores vary considerably by mothers' nativity and household linguistic isolation;
      a result that is largely influenced by the greater likelihood of living in
      poverty for children in linguistically isolated homes. The level of linguistic
      isolation in the community is also associated with cognitive scores but the
      greatest variation in scores across communities occurs among children of US born
      mothers.

PMID- 23146604
TI  - Beyond good grades: School composition and immigrant youth participation in
      extracurricular activities.
AB  - Past research has typically focused on educational attainment and achievement to
      understand the assimilation process for immigrant youth. However, academic
      achievement constitutes only part of the schooling experience. In this paper, we
      move beyond traditional measures such as test scores and dropout, and examine
      patterns of school-sponsored extracurricular activity participation. Analyzing
      data from Add Health and drawing upon the frog-pond and segmented assimilation
      frameworks, we find that immigrant minority youth are disadvantaged in regards to
      activity participation relative to the average student in high- compared to low
      SES schools. In high-SES schools, immigrant youth are less similar to their peers
      in terms of socioeconomic, race, and immigrant status, and as suggested by the
      frog-pond hypothesis, social comparison and ranking processes contribute to lower
      levels of social integration of immigrant youth into the school setting. We also
      find that as percent minority rises in high-SES schools, participation increases
      as well. The opposite pattern appears in low-SES schools: when percent minority
      increases, activity participation among immigrant minority students declines.
      These results are commensurate with both theoretical frameworks, and suggest that
      different mechanisms are at work in high- and low-SES schools. However, the
      effects of minority peers do not seem to hold for sports participation, and we
      also find that percent immigrant operates differently from percent minority,
      depressing the probability of activity participation across both high- and low
      SES schools. The main implication of our results is that racially diverse, higher
      SES schools are the most favorable contexts for the social integration of
      immigrant minority youth as well as third- and later-generation blacks and
      Hispanics.

PMID- 23146605
TI  - Youth employment and substance use.
AB  - A significant portion of teens work while in school and the consequences of that
      work are of potential concern to society. While there is widespread support for
      combining work and school, and some evidence that employment has positive effects
      on youth development, previous research has revealed some potentially harmful
      consequences of employment among teens. In this paper, we investigate the
      relationship between teen employment and substance use. We extended this
      literature by studying two different cohorts of youth, and by exploiting arguably
      exogenous variation in youth employment and earnings caused by changes in minimum
      wages and the business cycle (unemployment). Estimates suggest that hours of work
      are positively associated with alcohol and cigarette use. However, if selection
      on unobserved variables were equal to selection on observed variables, these
      associations would be close to zero. With respect to the association between
      earnings and substance use, the evidence is less clear.

PMID- 23146606
TI  - Family structure instability and mobility: The consequences for adolescents'
      problem behavior.
AB  - Adolescents who experience changes in parents' union status are more likely than
      adolescents in stable family structures to engage in problem behavior. We ask
      whether the link between family structure transitions and problem behavior in
      adolescence may be explained in part by the residential and school mobility that
      co-occur with family structure change. Our analysis uses nationally
      representative data from a two-generation study to assess the relative effects of
      family instability and mobility on the self-reported problem behavior of
      adolescents who were 12-17years old in 2006. Residential and school mobility only
      minimally attenuate the association of family structure changes with behavior
      problems for younger girls and older adolescents. Exposure to peer pressure has a
      larger attenuating effect. We conclude that although mobility often co-occurs
      with family structure change, it has independent effects on problem behavior.

PMID- 23146607
TI  - Latino immigration and White, Black, and Latino violent crime: A comparison of
      traditional and non-traditional immigrant destinations.
AB  - Despite a resurgent interest in the macro-level relationship between Latino
      immigration and violent crime, research has overlooked an important shift in
      immigrant settlement whereby Latino migrants are increasingly bypassing
      traditional receiving communities in favor of non-traditional ones. Additionally,
      how the impact of this new settlement pattern on violence is conditioned by race
      and ethnicity has yet to be explored. Using year 2000 race/ethnic-specific arrest
      data for 326 California, New York, and Texas census places, the current study
      explores the relationship between recent Latino immigration and White, Black, and
      Latino violent crime across both traditional and non-traditional immigrant
      destinations. Results suggest that (1) recent Latino immigration is generally
      unassociated with violence across all communities, (2) recent Latino immigration
      is associated with decreased violence in traditional destinations but slightly
      increased violence in non-traditional destinations, and (3) there are important
      race/ethnic differences in these relationships. Implications and directions for
      future research are discussed.

PMID- 23146608
TI  - Do magnitudes of difference on status characteristics matter for small group
      inequalities?
AB  - The theory of status characteristics and expectation states (SCT) explains how
      macro-level dimensions of stratification and specific abilities come to organize
      small group processes. The theory argues that people generate expectation states
      for each other based on relative standings on dimensions of stratification such
      that people with the more culturally valued states of the characteristics have
      higher expectations. Subsequently social influence, participation rates and
      evaluations of participation are purported to be directly related to expectation
      states. The result of this process is that large-scale inequalities are
      perpetuated in small group interactions, and individuals higher on abilities
      receive systematic advantages in small groups. SCT has received substantial
      experimental support for over 40years. However, the theory assumes that only
      states of relatively high and relatively low matter. That is, the theory and its
      applications assume that the magnitude of difference separating individuals on a
      dimension of stratification or ability is irrelevant. Recently, though,
      extensions to both the theory and its mathematics have been introduced that allow
      the magnitude of difference to be incorporated into the theory's predictions,
      supposedly yielding more precise predictions. This paper offers an experimental
      test of these procedures, showing that including the magnitude of difference into
      the theoretical predictions yields more precise estimates that explain more
      status-based inequalities.

PMID- 23146609
TI  - Reputation systems, aggression, and deterrence in social interaction.
AB  - Why do individuals sometimes pursue apparently senseless aggression, whether on
      the street, in court, at work, or in politics? Past work converges on the idea
      that individuals do so to establish social rank and deter prospective
      challengers. However, the fundamental claims of this argument - that concerns for
      one's reputation cause individuals to behave aggressively, and that a reputation
      for aggression deters threats from others - remain controversial. This paper
      offers a theoretical argument linking concern for reputation to aggressive
      behavior and deterrence. The theory argues that in competitive interactions,
      determining one's likelihood of prevailing in conflict ("competitive ability") is
      crucial for deciding whether to pursue conflict, but also rife with uncertainty.
      This motivates individuals to engage in aggressive behavior to signal to others
      (perhaps falsely) that they are strong competitors. Two behavioral experiments
      test this argument, and find that reputation systems motivate aggressive
      behavior, competitive ability moderates this effect, and reputations for
      aggressive behavior deter aggression from others. The results contribute to
      understanding the role reputation systems play in the social organization of
      aggressive behavior.

PMID- 23146610
TI  - Convenient yet not a convenience sample: Jury pools as experimental subject
      pools.
AB  - Scholars greatly benefit from access to convenient, inexpensive data sources.
      Many researchers rely on student subject pools, a practice that raises concern
      about the "college sophomore problem," or the possibility that findings from
      student subjects do not generalize beyond the campus. As an accessible, low cost,
      and heterogeneous data source, some researchers have used subjects recruited from
      jury pools, which are drawn from randomly-selected citizens required by law to
      appear for jury duty. In this paper, we discuss the strengths and weaknesses of
      this approach. First, we review pragmatic considerations involving access to jury
      pools, substantive content, the administration of survey-experiments, and the
      financial costs and benefits of this approach. Next, we present evidence
      regarding the quality of jury pool samples in terms of response rates, diversity,
      and representativeness. We conclude that jury pools, given proper attention to
      their limitations, offer an attractive addition to the viable sources of
      experimental data.

PMID- 23146611
TI  - Midlife vascular risk factors and their association with dementia deaths: results
      from a Norwegian prospective study followed up for 35 years.
AB  - There is growing evidence that midlife risk factors for vascular disease also are
      risk factors for dementia, but there is still need for long-term observational
      studies to address this. Our objective was to investigate the association of
      midlife vascular disease risk factors with dementia death. Participants were
      included in The Norwegian Counties Study (NCS) in the period 1974-78, aged 35-50
      years at baseline. Information from NCS was linked with the Cause of Death
      Registry through the year 2009 using the unique personal identification number.
      The study included 48,793 participants, 1.5 million person years and 486 dementia
      deaths (187 Alzheimer's; 299 non-Alzheimer's dementia). Cox regression for cause
      specific hazards was used. Dementia death was associated with increased total
      cholesterol levels (>7.80 vs. <5.20 mmol/l: HR=2.01, 95% confidence interval 1.37
      2.93); diabetes (HR=2.43, 95% CI 1.40-4.32) and low body mass index (<20 kg/m(2)
      vs. 20-25 kg/m(2): HR=1.76, 95% CI 1.15-2.68) in midlife. The associations
      remained after adjustment for other vascular risk factors and educational level.
      Smoking status or blood pressure in midlife was not significantly associated with
      risk of dementia death, although the results indicate a possible increased risk
      in heavy smokers. People suffering from high cholesterol levels, diabetes or
      underweight in midlife are at increased risk of dying from or with dementia later
      in life. Our findings add to previous results suggesting that intervention in
      midlife may be important. To better understand the mechanisms involved in the
      associations between midlife underweight, diabetes, and elevated cholesterol
      level and late-life dementia death, these links need to be further investigated.

PMID- 23146612
TI  - Acute but transient neurological deterioration revealing adult polyglucosan body
      disease.
AB  - Adult polyglucosan body disease (APBD) is a metabolic disorder usually caused by
      glycogen branching enzyme (GBE) deficiency. APBD associates progressive walking
      difficulties, bladder dysfunction and, in about 50% of the cases, cognitive
      decline. APBD is characterized by a recognizable leukodystrophy on brain MRI. We
      report here a novel presentation of this disease in a 35-year old woman who
      presented with an acute deterioration followed by an unexpected recovery.
      Enzymatic analysis displayed decreased GBE activity in leukocytes. Molecular
      analyses revealed that only one mutated allele was expressed, bearing a
      p.Arg515His mutation. This is the first observation reporting acute and
      reversible neurological symptoms in APBD. These findings emphasize the importance
      of searching GBE deficiency in patients presenting with a leukodystrophy and
      acute neurological symptoms mimicking a stroke, in the absence of cardiovascular
      risk factors.

PMID- 23146613
TI  - Chronic inflammatory demyelinating polyneuropathy.
AB  - Chronic inflammatory demyelinating polyneuropathy (CIDP) is the commonest
      treatable neuropathy in the western world. Untreated it may result in severe
      disability but if diagnosed and treated early there is effective treatment for
      the majority of patients. Typical CIDP is readily recognised but the diagnosis of
      other subgroups can be more challenging. The pathology of
      polyradiculoneuropathies such as CIDP characteristically affects the most
      proximal regions of the peripheral nervous system, nerve roots and major
      plexuses. It is important to test these regions with electrodiagnostic studies
      since routine neurophysiology may not encounter regions of pathology. Although
      accepted as an autoimmune disorder with an underlying immunopathology involving T
      cell and B cell responses, there is no agreement on major target antigens;
      however recent studies have highlighted a role for molecules in non compact
      myelin which play an essential role in the formation and maintenance of the nodal
      structures and hence in the function of ion channels central to saltatory
      conduction. Controlled trials have proven the efficacy of corticosteroid,
      intravenous immunoglobulin and plasma exchange in the short term and intravenous
      immunoglobulin also in the long term. Immunosuppressive agents are widely used
      but their efficacy has not been proven in controlled trials. Recent trials have
      shown the importance of attempting treatment withdrawal in patients apparently in
      remission to conserve treatments that are very expensive and in short supply,
      since a significant proportion of patients may enter long lasting remission
      following short term therapy. For the relatively small group of patients who do
      not respond to these first line therapies new agents including monoclonal
      antibodies may have a role. 

PMID- 23146614
TI  - Relevance of bleeding pattern on clinical appearance and outcome in patients with
      hemorrhagic brain arteriovenous malformations.
AB  - Although several descriptions of the angioarchitectural features of brain
      arteriovenous malformations (AVMs) associated with higher hemorrhagic risk have
      been reported, the prognostic value of the different bleeding patterns still
      needs to be elucidated. This study evaluated the influence on clinical appearance
      and outcome of the parenchymal and non-parenchymal (subarachnoid hemorrhage-SAH
      and intraventricular hemorrhage-IVH) bleedings associated with ruptured AVMs.
      Clinical records and neuroradiological examinations of 30 patients with
      hemorrhagic AVMs were reviewed in order to identify their angioarchitectural
      features and the associated bleeding pattern. These data along with demographic
      characteristics and treatment modality were dichotomized and their relationship
      with clinical status at admission and follow-up was tested. IVH as well as
      parenchymal hematomas larger than 20 cm(3) appeared associated with a severe
      clinical status at admission, whereas SAH involving basal cisterns was
      significantly associated with unfavorable outcome. Age, sex and
      angioarchitectural features did not show significant association with the
      severity of the prognosis. However, none of these bleeding patterns appeared as
      an independent risk factor of poor outcome at multivariate analysis. In
      conclusion, our data emphasized the possibility that non-parenchymal bleeding may
      worsen the outcome of patients with hemorrhagic AVMs.

PMID- 23146615
TI  - Assessment of swallowing in motor neuron disease and Asidan/SCA36 patients with
      new methods.
AB  - BACKGROUND: We report on a unique complication of cerebellar ataxia and motor
      neuron disease named Asidan/SCA36 with a high frequency of tongue atrophy. We
      aimed to elucidate dysphagia in amyotrophic lateral sclerosis (ALS) and spinal,
      bulbar muscular atrophy (SBMA), and Asidan/SCA36 patients with new methods.
      METHODS: Patients diagnosed with ALS (n=20), SBMA (n=6), and Asidan (n=12) were
      included. A videofluoroscopic swallow study (VFS), an assessment of maximal
      tongue pressure (MTP), and impedance pharyngography (IPG) were applied. RESULTS:
      The frequencies of VFS abnormalities were 70%, 50%, and 33% in ALS, SBMA, and
      Asidan/SCA36, respectively. Compared with control subjects (31.6 +/- 6.3 kPa,
      mean +/- SD), MTP was significantly decreased in ALS patients and SBMA patients,
      but was relatively preserved in Asidan patients. ALS patients performed more
      swallowing actions (Ns) detected by IPG than did control subjects, but SBMA and
      Asidan/SCA36 patients performed similar Ns to control subjects. CONCLUSIONS: VFS
      showed a higher frequency of swallowing abnormalities in ALS patients. MTP and
      IPG measurements showed the most severe involvement in ALS patients and a
      relatively preserved swallowing function in SBMA and Asidan/SCA36 patients.

PMID- 23146616
TI  - Electrophysiological features of lower motor neuron involvement in progressive
      supranuclear palsy.
AB  - BACKGROUND: Abnormalities of the spinal cord were considered uncommon in
      progressive supranuclear palsy (PSP), and therefore spinal symptoms were not
      included among PSP characteristic features. However there have been some
      neuropathological reports of spinal cord lesions in patients with PSP. The aim of
      our study was to find out if the possible lower motor neuron involvement in PSP
      is reflected by electromyographic (EMG) and/or electroneurographic (ENG)
      abnormalities. MATERIAL: 24 patients with clinically probable PSP (mean age 67.5
      yrs; 66% males) were included in the study. The control group for ENG studies
      consisted 25 age matched healthy volunteers. METHODS: Nerve conduction studies in
      the ulnar, peroneal and sural nerves and EMG of the first interosseus dorsal and
      tibial anterior muscles were performed. RESULTS: The only ENG abnormality
      observed was decreased compound muscle action potential (CMAP) and sensory nerve
      action potential (SNAP) amplitudes in the ulnar nerve. Such decrease was
      registered in 8.3% and 20% of PSP patients respectively. There was no significant
      difference between the values of ENG parameters between PSP patients and the
      control group. In EMG abnormalities suggesting chronic reinnervation were
      recorded in the first interosseous dorsal (FID) muscle in 45.8%, and in the
      tibialis anterior (TA) muscle in 37.5% of PSP patients. A significant correlation
      was found between the age of PSP patients and their mean motor unit potential
      (MUP) amplitude in TA muscle (p=0.04) and also between the age of onset and MUP
      amplitude in both, the TA and FID muscles (p=0.026 and p=0.03 respectively).
      CONCLUSIONS: In PSP, neurogenic EMG abnormalities in skeletal muscles are present
      in nearly half the patients suggesting a loss of motor neurons in the anterior
      horns of the spinal cord which is in line with our histopathological findings. In
      contrast, electrophysiological signs of neuropathy in peripheral nerves in PSP
      are very rare. Concluding, although PSP is characterized by the pathological
      process in specific basal ganglia and brainstem areas, our electromyographic
      study suggests the need for broadening the spectrum of PSP for lower motor
      neurons degeneration.

PMID- 23146617
TI  - Paradigm shifts in cardiovascular research from Caenorhabditis elegans muscle.
AB  - Research on Caenorhabditis elegans has led to the discovery of the consequences
      of mutation in myosin, its associated proteins, and the extracellular matrix
      membrane cytoskeleton complex. Key results include understanding thick filament
      structure and assembly, the regulation of sarcomeric protein turnover, and the
      organization of thick and thin filaments into ordered sarcomeres. These results
      are critical to studies of cardiovascular diseases such as the cardiomyopathies,
      congenital septal defects, aneurysms of the thoracic aorta, and cardiac
      remodeling in heart failure.

PMID- 23146618
TI  - Elevated serum S-100B levels in children with temporal lobe epilepsy.
AB  - PURPOSE: An elevated level of S-100B in serum is generally considered to be a
      biochemical marker of nervous tissue damage. According to our knowledge, no
      studies have evaluated the serum S-100B protein concentration in children with
      temporal lobe epilepsy. The objective of this study was to measure the serum
      levels of S-100B protein in pediatric cases with temporal epilepsy. METHODS: This
      case-controlled cross-sectional study was performed at the Department of
      Pediatric Neurology, Harran University School of Medicine, Sanliurfa, in Turkey.
      Serum S-100B protein levels were studied in 19 (12 females, 7 males) children
      with temporal lobe epilepsy and in 25 (15 females, 10 males) healthy control
      subjects. Serum samples were collected within 30min after a complex partial
      seizure, and serum S-100B protein levels were measured with an
      electrochemiluminescence immunoassay for the quantification of protein (ECLIA
      kit, Roche((r)) Diagnostics, Germany). RESULTS: The mean serum concentration of S
      100B protein was 0.12+/-0.02MUg/L in the temporal lobe epilepsy group and 0.07+/
      0.01MUg/L in the control group. The patients showed significantly elevated S-100B
      protein levels compared with healthy controls (P<0.001). CONCLUSION: Our data
      suggest that increased S-100B protein levels in the serum might reflect neuronal
      damage in the brains of children with temporal lobe epilepsy. These results do
      confirm the previous findings of elevated S-100B protein levels in adult patients
      with temporal lobe epilepsy.

PMID- 23146619
TI  - Antipsychotics and seizures: higher risk with atypicals?
AB  - PURPOSE: Almost all antipsychotics have been associated with a risk of epileptic
      seizure provocation. Among the first-generation antipsychotics (FGA)
      chlorpromazine appears to be associated with the greatest risk of seizures among
      the second-generation antipsychotics (SGA) clozapine is thought to be most likely
      to cause convulsions. This information is largely based on studies that are not
      sufficiently controlled. Besides, information about the seizure risk associated
      with newer antipsychotics is scarce. METHOD: The Pharmacovigilance Unit of the
      Basque Country (network of centers of the Spanish Pharmacovigilance System, SEFV)
      provided reporting data for adverse reactions (AR) from the whole SEFV to
      estimate the reporting odds ratio (ROR) for antipsychotics and seizures
      ("convulsions" as Single MedDra Query). Data was obtained from SEFV database from
      1984 to the June 2011. RESULTS: The total number of convulsions reported for SGA
      was 169 (total reported AR 3.204). The number of convulsions reported for FGA was
      35 (total reported AR 2.051). 94 convulsions were reported in association with
      clozapine (total AR 1.052). The ROR for SGA versus FGA was 3.2 (CI 95%: 2.21
      4.63). The ROR for SGA excluding clozapine versus FGA was 2.08 (CI 95%: 1.39
      3.12). CONCLUSION: Our results show that SGA may pose a higher risk of seizures
      than FGA, mainly, but not only due to clozapine. This is line with recent studies
      suggesting that some SGA carried a higher average risk of electroencephalographic
      abnormalities than many FGA. Nonetheless, It is well known that spontaneous
      reports do not allow strong inferences about adverse drug effects, because
      differences in reporting fractions by time, drug or type of event are difficult
      or even impossible to distinguish from differences in the occurrence rates of
      adverse events. Still, we consider that the possibility of SGA carrying a higher
      risk of seizure induction than FGA warrants further research.

PMID- 23146620
TI  - Can inhA mutation predict ethionamide resistance?
AB  - SETTING: A tertiary care centre in Mumbai, India. OBJECTIVE: To estimate the
      extent of association between inhA mutant isoniazid (INH) resistant strains and
      ethionamide (ETH) resistance. DESIGN: A total of 140 clinical isolates processed
      for INH and ETH phenotypic drug  susceptibility testing, and molecularly
      processed with the line-probe assay (LPA) Genotype(r) MTBDRplus, were considered.
      RESULTS: Among the 112 phenotypically determined INH-resistant strains, 69
      (61.6%) strains were ETH-resistant. An inhA promoter mutation was identified  in
      24 (21.4%) INH-resistant isolates, 21 (87.5%) of which were ETH-resistant (P <
      0.0001). CONCLUSION: An inhA promoter mutation could be considered as a marker
      for the determination of ETH resistance in India, where the use of LPA is being
      expanded.

PMID- 23146621
TI  - Changes in GABAergic inputs in the paraventricular nucleus maintain sympathetic
      vasomotor tone in chronic heart failure.
AB  - The paraventricular nucleus (PVN) of the hypothalamus is an important region of
      the brain involved in the regulation of sympathetic vasomotor tone. Accumulating
      evidence supports the idea that a change in hypothalamic gamma-aminobutyric acid
      (GABA)-ergic inhibitory and glutamatergic excitatory inputs contribute to the
      exacerbated sympathetic drive in chronic heart failure (HF). The purpose of this
      study was to determine whether a possible imbalance between glutamatergic and
      GABAergic inputs to the PVN contributes to increased sympathetic outflow in HF in
      two different sympathetic territories. Renal (RSNA) and splanchnic sympathetic
      nerve activity (SSNA), mean arterial blood pressure (MAP) and heart rate were
      recorded from urethane-anesthetized HF or sham rats. The NMDA-glutamate and GABA
      A receptor densities within the PVN were quantified in HF and sham rats by
      autoradiography. Bilateral microinjection of kynurenic acid (4nmol) into the PVN
      decreased MAP and RSNA and SSNA in HF but not in sham rats. Furthermore, in
      response to GABA-A blockade in the PVN by bicuculline (400 pmol), hypertension
      and SSNA were reduced in HF compared to sham. The quantification of ionotropic
      NMDA receptors and GABA-A receptors in the PVN showed a significant reduction of
      GABA-A in HF rats; however, the NMDA density in the PVN did not differ between
      groups. Thus, this study provides evidence that the sympathoexcitation is
      maintained by an imbalance between GABAergic and glutamatergic inputs in the PVN
      in HF. The reduced GABAergic input results in relatively augmented glutamatergic
      actions in the PVN of HF rats.

PMID- 23146622
TI  - Differential distribution of voltage-gated channels in myelinated and
      unmyelinated baroreceptor afferents.
AB  - Voltage gated ion channels (VGC) make possible the frequency coding of arterial
      pressure and the neurotransmission of this information along myelinated and
      unmyelinated fiber pathways. Although many of the same VGC isoforms are expressed
      in both fiber types, it is the relative expression of each that defines the
      unique discharge properties of myelinated A-type and unmyelinated C-type
      baroreceptors. For example, the fast inward Na+ current is a major determinant of
      the action potential threshold and the regenerative transmembrane current needed
      to sustain repetitive discharge. In A-type baroreceptors the TTX-sensitive
      Na(v)1.7 VGC contributes to the whole cell Na+ current. Na(v)1.7 is expressed at
      a lower density in C-type neurons and in conjunction with TTX-insensitive
      Na(v)1.8 and Na(v)1.9 VGC. As a result, action potentials of A-type neurons have
      firing thresholds that are 15-20 mV more negative and upstroke velocities that
      are 5-10 times faster than unmyelinated C-type neurons. A more depolarized
      threshold in conjunction with a broader complement of non-inactivating K(V) VGC
      subtypes produces C-type action potentials that are 3-4 times longer in duration
      than A-type neurons and at markedly lower levels of cell excitability.
      Unmyelinated baroreceptors also express KCa1.1 which provides approximately 25%
      of the total outward K+ current. KCa1.1 plays a critically important role in
      shaping the action potential profile of C-type neurons and strongly impacts
      neuronal excitability. A-type neurons do not functionally express the KCa1.1
      channel despite having a whole cell Ca(V) current quite similar to that of C-type
      neurons. As a result, A-type neurons do not have the frequency-dependent braking
      forces of KCa1.1. Lack of a KCa current and only a limited complement of non
      inactivating K(V) VGC in addition to a hyperpolarization activated HCN1 current
      that is nearly 10 times larger than in C-type neurons leads to elevated levels of
      discharge in A-type neurons, a hallmark of myelinated baroreceptors.
      Interestingly, HCN2 and HCN4 expression levels are comparable in both fiber
      types. Collectively, such apportion of VGC constrains the neural coding of
      myelinated A-type baroreceptors to low threshold, high frequency, high fidelity
      discharge but with a limited capacity for neuromodulation of afferent bandwidth.
      Unmyelinated C-type baroreceptors require greater depolarizing forces for spike
      initiation and have a low frequency discharge profile that is often poorly
      correlated with the physiological stimulus. But the complement of VGC in C-type
      neurons provides far greater capacity for neuromodulation of cell excitability
      than can be obtained from A-type baroreceptors.

PMID- 23146623
TI  - Electrical carotid sinus stimulation in treatment resistant arterial
      hypertension.
AB  - Treatment resistant arterial hypertension is commonly defined as blood pressure
      that remains above goal in spite of the concurrent use of three antihypertensive
      agents of different classes. The sympathetic nervous system promotes arterial
      hypertension and cardiovascular as well as renal damage, thus, providing a
      logical treatment target in these patients. Recent physiological studies suggest
      that baroreflex mechanisms contribute to long-term control of sympathetic
      activity and blood pressure providing an impetus for the development of
      electrical carotid sinus stimulators. The concept behind electrical stimulation
      of baroreceptors or baroreflex afferent nerves is that the stimulus is sensed by
      the brain as blood pressure increase. Then, baroreflex efferent structures are
      adjusted to counteract the perceived blood pressure increase. Electrical
      stimulators directly activating afferent baroreflex nerves were developed years
      earlier but failed for technical reasons. Recently, a novel implantable device
      was developed that produces an electrical field stimulation of the carotid sinus
      wall. Carefully conducted experiments in dogs provided important insight in
      mechanisms mediating the depressor response to electrical carotid sinus
      stimulation. Moreover, these studies showed that the treatment success may depend
      on the underlying pathophysiology of the hypertension. Clinical studies suggest
      that electrical carotid sinus stimulation attenuates sympathetic activation of
      vasculature, heart, and kidney while augmenting cardiac vagal regulation, thus
      lowering blood pressure. Yet, not all patients respond to treatment. Additional
      clinical trials are required. Patients equipped with an electrical carotid sinus
      stimulator provide a unique opportunity gaining insight in human baroreflex
      physiology.

PMID- 23146624
TI  - Successful treatment of thyrotoxicosis is accompanied by a decrease in serum
      sclerostin levels.
AB  - Sclerostin, a product of a SOST gene, is a protein expressed by osteocytes that
      inhibits osteoblastic bone formation. Several hormones, including PTH and
      glucocorticosteroids, have been suggested to be possible regulators of sclerostin
      production. The influence of thyroid hormones on sclerostin synthesis has not
      been investigated, so far. The aim of the study was to evaluate sclerostin
      concentrations in patients before and after treatment of thyrotoxicosis. PATIENTS
      AND METHODS: The study involved 15 patients (4 men), mean age 51.8+/-15.3 years,
      mean BMI value - 24.7+/-3.5, with thyrotoxicosis due to Graves' disease or toxic
      multinodular goitre. Serum sclerostin was measured by immunoassay at diagnosis of
      thyrotoxicosis and after 6-10 weeks of treatment with thiamazole. The data were
      analysed by means of simple descriptive statistics of location and dispersion and
      Mann-Whitney U test for pairs of results, before and after thiamazole therapy.
      Association between variables was evaluated with use of Spearman's correlation
      coefficient. RESULTS: There was a significant decrease in free T3 (FT3) and free
      T4 (FT4) concentrations (from 8.74+/-4.79 pg/ml to 3.54+/-2.40 pg/ml, and from
      4.48+/-2.21 ng/ml to 1.02+/-1.07 ng/ml, respectively, p<0.001). This was
      accompanied by a marked decrease of serum sclerostin levels from 55.46+/-20.90
      pmol/l to 35.73+/-15.70 pmol/l, p<0.0015). Interestingly, enough, sclerostin
      levels did not correlate with serum FT3 or FT4 concentrations. CONCLUSIONS:
      Restoration of a euthyroid state in patients with thyrotoxicosis results in a
      significant decrease in serum sclerostin concentrations. The above mentioned
      phenomenon may reflect lowering of bone metabolism, but a possible direct
      influence of thyroid hormones on SOST gene needs to be investigated.

PMID- 23146625
TI  - Postconcussive complaints, cognition, symptom attribution and effort among
      veterans.
AB  - The etiology of postconcussive symptoms is not clearly understood. Development of
      etiological models of those symptoms will be helpful for accurate diagnosis and
      for planning effective treatment. Such a model should characterize the role of
      subject characteristics (education, premorbid intelligence), social psychological
      factors and symptom validity. Toward that end, the present study examined the
      association of postconcussive complaints and cognitive performance with symptom
      attribution and level of effort on testing. In a sample of 155 veterans,
      attribution to concussion was associated with endorsement of more severe
      postconcussive complaints, after controlling for the effects of other factors
      such as subject characteristics. Similarly, effort was associated with cognitive
      performance after controlling for the effects of these other factors. The present
      findings are consistent with previous reports that illness perception and effort
      on testing are associated with postconcussive complaints. This supports previous
      recommendations to routinely educate all concussion patients immediately after
      injury to reduce distorted perceptions and related persistent complaints.
      Finally, these findings highlight a need for routine assessment of patients'
      perception of their injury to identify cases that may require psychotherapy to
      address any misattributions that develop.

PMID- 23146626
TI  - Organizational issues in the implementation and adoption of health information
      technology innovations: an interpretative review.
AB  - PURPOSE: Implementations of health information technologies are notoriously
      difficult, which is due to a range of inter-related technical, social and
      organizational factors that need to be considered. In the light of an apparent
      lack of empirically based integrated accounts surrounding these issues, this
      interpretative review aims to provide an overview and extract potentially
      generalizable findings across settings. METHODS: We conducted a systematic search
      and critique of the empirical literature published between 1997 and 2010. In
      doing so, we searched a range of medical databases to identify review papers that
      related to the implementation and adoption of eHealth applications in
      organizational settings. We qualitatively synthesized this literature extracting
      data relating to technologies, contexts, stakeholders, and their inter
      relationships. RESULTS: From a total body of 121 systematic reviews, we
      identified 13 systematic reviews encompassing organizational issues surrounding
      health information technology implementations. By and large, the evidence
      indicates that there are a range of technical, social and organizational
      considerations that need to be deliberated when attempting to ensure that
      technological innovations are useful for both individuals and organizational
      processes. However, these dimensions are inter-related, requiring a careful
      balancing act of strategic implementation decisions in order to ensure that
      unintended consequences resulting from technology introduction do not pose a
      threat to patients. CONCLUSIONS: Organizational issues surrounding technology
      implementations in healthcare settings are crucially important, but have as yet
      not received adequate research attention. This may in part be due to the
      subjective nature of factors, but also due to a lack of coordinated efforts
      toward more theoretically-informed work. Our findings may be used as the basis
      for the development of best practice guidelines in this area.

PMID- 23146628
TI  - Commenting on the effects of surface treated- and non-surface treated TiO(2) in
      the Caco-2 cell model.
AB  - In a recent work published in Particle and Fibre Toxicology by Fisichella and
      coworkers investigating surface-modified TiO2 nanoparticle exposure in a model
      human intestinal epithelium (Caco-2), albeit degraded to mimic conditions in the
      gut and exposure to natural sunlight, purportedly resulted in no toxic effects.
      The authors (Fisichella et al.) claim to have confirmed the results of a 2010
      report by Koeneman et al. However, the study by Koeneman and colleagues revealed
      significant effects of unmodified TiO2 nanoparticles. These contradicting data
      warrant further investigation into the possible effects of aluminum hydroxide, as
      these nanoparticles appear to have resulted in an abnormal apical surface in Caco
      2 cells.

PMID- 23146627
TI  - Hospital collaboration with emergency medical services in the care of patients
      with acute myocardial infarction: perspectives from key hospital staff.
AB  - STUDY OBJECTIVE: Evidence suggests that active collaboration between hospitals
      and emergency medical services (EMS) is significantly associated with lower acute
      myocardial infarction mortality rates; however, the nature of such collaborations
      is not well understood. We seek to characterize views of key hospital staff about
      collaboration with EMS in the care of patients hospitalized with acute myocardial
      infarction. METHODS: We performed an exploratory analysis of qualitative data
      previously collected from site visits and detailed interviews with 11 US
      hospitals that ranked in the top or bottom 5% of performance on 30-day risk
      standardized acute myocardial infarction mortality rates, using Centers for
      Medicare & Medicaid Services data from 2005 to 2007. We selected all codes from
      the previous analysis in which EMS was most likely to have been discussed. A
      multidisciplinary team analyzed the data with the constant comparative method to
      generate recurrent themes. RESULTS: Both higher- and lower-performing hospitals
      reported that EMS is critical to the provision of timely care for patients with
      acute myocardial infarction. However, close collaborative relationships with EMS
      were more apparent in the higher-performing hospitals, which demonstrated
      specific investment in and attention to EMS through respect for EMS as valued
      professionals and colleagues, strong communication and coordination with EMS and
      active engagement of EMS in hospital acute myocardial infarction quality
      improvement efforts. CONCLUSION: Hospital staff from higher-performing hospitals
      described broad, multifaceted strategies to support collaboration with EMS in
      providing acute myocardial infarction care. The association of these strategies
      with hospital performance should be tested quantitatively in a larger
      representative study.

PMID- 23146629
TI  - Subclinical myopathy in a child with neutral lipid storage disease and mutations
      in the PNPLA2 gene.
AB  - We report a 14-year-old-boy with markedly elevated serum creatine kinase (CK)
      levels, in whom massive triglyceride storage was found in peripheral blood
      leukocytes and in muscle biopsy. Sequencing PNPLA2, the gene encoding the adipose
      triglyceride lipase (ATGL) and responsible for the neutral lipid storage disease
      with myopathy (NLSDM), we identified two heterozygous mutations, including a
      previously reported nonsense and a novel missense mutation in the patatin domain
      of the gene. Lipid storage myopathy can be clinically silent in childhood and
      presenting only with hyperCKemia.

PMID- 23146630
TI  - CYLD, a deubiquitinase specific for lysine63-linked polyubiquitins, accumulates
      at the postsynaptic density in an activity-dependent manner.
AB  - Polyubiquitin chains on proteins flag them for distinct fates depending on the
      type of polyubiquitin linkage. While lysine48-linked polyubiquitination directs
      proteins to proteasomal degradation, lysine63-linked polyubiquitination promotes
      different protein trafficking and is involved in autophagy. Here we show that
      postsynaptic density (PSD) fractions from adult rat brain contain deubiquitinase
      activity that targets both lysine48 and lysine63-linked polyubiquitins.
      Comparison of PSD fractions with parent subcellular fractions by Western
      immunoblotting reveals that CYLD, a deubiquitinase specific for lysine63-linked
      polyubiquitins, is highly enriched in the PSD fraction. Electron microscopic
      examination of hippocampal neurons in culture under basal conditions shows
      immunogold label for CYLD at the PSD complex in approximately one in four
      synapses. Following depolarization by exposure to high K+, the proportion of CYLD
      labeled PSDs as well as the labeling intensity of CYLD at the PSD increased by
      more than eighty percent, indicating that neuronal activity promotes accumulation
      of CYLD at the PSD. An increase in postsynaptic CYLD following activity would
      promote removal of lysine63-polyubiquitins from PSD proteins and thus could
      regulate their trafficking and prevent their autophagic degradation.

PMID- 23146631
TI  - Molecular docking and NMR binding studies to identify novel inhibitors of human
      phosphomevalonate kinase.
AB  - Phosphomevalonate kinase (PMK) phosphorylates mevalonate-5-phosphate (M5P) in the
      mevalonate pathway, which is the sole source of isoprenoids and steroids in
      humans. We have identified new PMK inhibitors with virtual screening, using
      autodock. Promising hits were verified and their affinity measured using NMR
      based (1)H-(15)N heteronuclear single quantum coherence (HSQC) chemical shift
      perturbation and fluorescence titrations. Chemical shift changes were monitored,
      plotted, and fitted to obtain dissociation constants (K(d)). Tight binding
      compounds with K(d)'s ranging from 6-60 MUM were identified. These compounds
      tended to have significant polarity and negative charge, similar to the natural
      substrates (M5P and ATP). HSQC cross peak changes suggest that binding induces a
      global conformational change, such as domain closure. Compounds identified in
      this study serve as chemical genetic probes of human PMK, to explore pharmacology
      of the mevalonate pathway, as well as starting points for further drug
      development.

PMID- 23146632
TI  - Visualization of cyclooxygenase-2 using a 2,3-diarylsubstituted indole-based
      inhibitor and confocal laser induced cryofluorescence microscopy at 20K in
      melanoma cells in vitro.
AB  - This study aimed at visualization of cyclooxygenase-2 (COX-2) protein expression
      in melanoma cells by confocal laser induced cryofluorescence microscopy using 4
      (3-(4-methoxyphenyl)-1H-indol-2-yl)benzene-sulfonamide (C1) representative for a
      novel class of autofluorescent 2,3-diarylsubstituted indole-based selective COX-2
      inhibitors. COX-2 expression was measured in human melanoma cell lines A2058 and
      MelJuso by immunocytochemistry and immunoblotting. Cellular uptake experiments
      using varying C1 concentrations down to 0.1 nM (with/without molar excess of
      celecoxib as control) were performed at 37  degrees C. Cryofluorescence
      microscopy was conducted at 20 K. COX-2 protein expression was successfully
      visualized by C1 in A2058 cells. COX-2-negative MelJuso cells showed no specific
      accumulation of C1. Control experiments using celecoxib and, additionally,
      implemented fluorescence spectroscopy confirmed specificity of both cellular
      uptake and intracellular association of C1. Cryofluorescence microscopy in
      combination with spectroscopy allowed for visualization of COX-2 protein
      expression in melanoma cells in vitro using a selective COX-2 inhibitor at very
      low concentrations.

PMID- 23146633
TI  - Good manufacturing practice-compliant animal-free expansion of human bone marrow
      derived mesenchymal stroma cells in a closed hollow-fiber-based bioreactor.
AB  - Mesenchymal stroma cells (MSC) are increasingly recognized for various
      applications of cell-based therapies such as regenerative medicine or
      immunomodulatory treatment strategies. Standardized large-scale expansions of MSC
      under good manufacturing practice (GMP)-compliant conditions avoiding animal
      derived components are mandatory for further evaluation of these novel
      therapeutic approaches in clinical trials. We applied a novel automated hollow
      fiber cell expansion system (CES) for in vitro expansion of human bone marrow
      derived MSC employing a GMP-compliant culture medium with human platelet lysate
      (HPL). Between 8 and 32 ml primary bone marrow aspirate were loaded into the
      hollow fiber CES and cultured for 15-27 days. 2-58 million MSC were harvested
      after primary culture. Further GMP-compliant cultivation of second passage MSC
      for 13 days led to further 10-20-fold enrichment. Viability, surface antigen
      expression, differentiation capacity and immunosuppressive function of MSC
      cultured in the hollow fiber CES were in line with standard criteria for MSC
      definition. We conclude that MSC can be enriched from primary bone marrow
      aspirate in a GMP-conform manner within a closed hollow fiber bioreactor and
      maintain their T lymphocyte inhibitory capacity. Standardized and reliable
      conditions for large scale MSC expansion pave the way for safe applications in
      humans in different therapeutic approaches.

PMID- 23146634
TI  - Soluble oligomers and fibrillar species of amyloid beta-peptide differentially
      affect cognitive functions and hippocampal inflammatory response.
AB  - Two major active species of beta-amyloid protein (Abeta), fibrillar Abeta1-42
      (FAbeta) and soluble Abeta1-42 oligomers (AbetaO), are known to play important
      roles in the pathogenesis of Alzheimer's disease. However, the differences
      between them are largely unknown. In this study, we explored the effects of
      FAbeta and AbetaO on cognitive functions and hippocampal inflammatory response
      through a 30-days infusion of FAbeta or AbetaO (144pmol/d) into the left lateral
      ventricles of the rat brain. Morris water maze showed that the impairment of
      learning and memory functions was much more significant in the AbetaO-infused
      rats, compared to the FAbeta-infused rats. AbetaO-induced neurodegeneration and
      ultrastructure damage in CA1 neurons were more remarkable than those induced by
      FAbeta. Compared to FAbeta, AbetaO exerted more potent effects on the expressions
      of inflammatory factors toll-like receptor 4 and TNF-alpha and activation of NF
      kappaB signaling. Taken together, our results from in vivo model demonstrate that
      AbetaO is more neurotoxic than FAbeta, and this neurotoxicity may be related to
      NF-kappaB-medicated inflammatory response.

PMID- 23146635
TI  - The inhibitory effect of curcumin on voltage-dependent K+ channels in rabbit
      coronary arterial smooth muscle cells.
AB  - We investigated the effects of curcumin, the principal active compound of
      turmeric, on voltage-dependent K(+) (Kv) channels in freshly isolated rabbit
      coronary arterial smooth muscle cells using the voltage-clamp technique. Curcumin
      reduced the Kv current in a dose-dependent manner with an apparent K(d) value of
      1.07 +/- 0.03 MUM. Although curcumin did not alter the kinetics of Kv current
      activation, it predominantly accelerated the decay rate of channel inactivation.
      The association and dissociation rate constants of curcumin were 1.35 +/- 0.05
      MUM(-1)s(-1) and 1.47 +/- 0.17s(-1), respectively. Curcumin did not alter the
      steady-state activation or inactivation curves. Application of train pulses (1 or
      2 Hz) increased curcumin-induced blockade of the Kv current, and the recovery
      time constant also increased in the presence of curcumin suggesting, that the
      inhibitory action of Kv currents by curcumin was use-dependent. From these
      results, we concluded that curcumin inhibited vascular Kv current in a state-,
      time-, and use-dependent manner.

PMID- 23146636
TI  - Effect of topical anesthesia on pain during infiltration injection and success of
      anesthesia for maxillary central incisors.
AB  - INTRODUCTION: This study was performed to investigate the effect of topical
      anesthesia on pain during needle penetration and infiltration injection as well
      as the effect of pain during injection on success rate of anesthesia in maxillary
      central incisors. METHODS: In a crossover double-blind study, 25 volunteers
      randomly received either topical anesthesia or placebo before infiltration
      injection with prilocaine for their maxillary central incisors in 2 separate
      appointments. The pain after needle penetration and during injection was
      separately recorded. An electric pulp tester was used to evaluate the success of
      the anesthetic injection. Data were analyzed by McNemar, Wilcoxon, and chi(2)
      tests. RESULTS: Overall for 50 injections, 72% of the teeth had successful
      anesthesia. No significant difference was found between placebo and topical
      anesthetic groups for the pain of needle penetration as well as pain during
      injection (P > .05). The volunteers who reported moderate-to-severe pain during
      injection showed no significant difference in the success rate of anesthesia
      compared with those with no or mild pain during injections (P > .05).
      CONCLUSIONS: Use of topical anesthesia had no significant effect on pain during
      either needle penetration or injection. Pain during injection had no significant
      effect on the success of anesthesia.

PMID- 23146637
TI  - Rigid versus flexible dentine-like endodontic posts--clinical testing of a
      biomechanical concept: seven-year results of a randomized controlled clinical
      pilot trial on endodontically treated abutment teeth with severe hard tissue
      loss.
AB  - INTRODUCTION: This is the first clinical long-term pilot study that tested the
      biomimetic concept of using more flexible, dentine-like (low Young modulus) glass
      fiber-reinforced epoxy resin posts (GFREPs) compared with rather rigid, stiff
      (higher Young modulus) titanium posts (TPs) in order to improve the survival rate
      of severely damaged endodontically treated teeth. METHODS: Ninety-one subjects in
      need of postendodontic restorations in teeth with 2 or less remaining cavity
      walls were randomly assigned to receive either a tapered TP (n = 46) or a tapered
      GFREP (n = 45). The posts were adhesively luted using self-adhesive resin cement.
      The composite core build-ups were prepared ensuring a circumferential 2-mm
      ferrule. The primary endpoint was a loss of restoration for any reason. To study
      group differences, the log-rank test was calculated (P < .05). Hazard plots were
      constructed. RESULTS: After 84 months of observation (mean = 71.2 months), 7
      restorations failed (ie, 4 GFREPs and 3 TPs). The failure modes were as follows:
      GFREP:root fracture (n = 3), core fracture (n = 1) and TP:endodontic failure (n =
      3). No statistical difference was found between the survival rates (GFREPs =
      90.2%, TPs = 93.5%, P = .642). The probability of no failure was comparable for
      both post materials (risk ratio; 95% confidence interval, 0.965-0.851/1.095).
      CONCLUSIONS: When using self-adhesive luted prefabricated posts in severely
      destroyed abutment teeth with 2 or less cavity walls and a 2-mm ferrule,
      postendodontic restorations achieved high long-term survival rates irrespective
      of the post material used (ie, glass fiber vs titanium).

PMID- 23146638
TI  - Anesthetic efficacy of the inferior alveolar nerve block in red-haired women.
AB  - INTRODUCTION: The exact reasons for failure of the inferior alveolar nerve (IAN)
      block are not completely known, but red hair could play a role. The genetic basis
      for red hair involves specific mutations, red hair color (RHC) alleles, in the
      melanocortin-1 receptor (MC1R) gene. The purpose of this prospective randomized
      study was to investigate a possible link between certain variant alleles of the
      MC1R gene or its phenotypic expression of red hair and the anesthetic efficacy of
      the IAN block in women. MATERIALS: One-hundred twenty-four adult female subjects
      (62 red haired and 62 dark haired) participated in this study. Dental anxiety was
      determined in each subject using the Corah Dental Anxiety Questionnaire. The
      subjects were given 2 cartridges of 2% lidocaine with 1:100,000 epinephrine via
      the IAN block. Pulpal anesthesia was measured in the posterior and anterior teeth
      in 4-minute cycles for 60 minutes using an electric pulp tester. The MC1R alleles
      were genotyped for each subject from cheek cells containing DNA collected using
      buccal swabs. RESULTS: Women with red hair and women with 2 RHC alleles reported
      significantly higher levels of dental anxiety compared with women with dark hair
      or women with 0 RHC alleles. No significant differences in anesthetic success
      were found between any of the groups for any of the teeth. CONCLUSIONS: Red hair
      and the MC1R gene were significantly linked to higher levels of dental anxiety
      but were unrelated to success rates of the IAN block in women with healthy pulps.

PMID- 23146639
TI  - Association among oral health, apical periodontitis, CD14 polymorphisms, and
      coronary heart disease in middle-aged adults.
AB  - INTRODUCTION: There is evidence to suggest that an association exists between
      oral infections and coronary heart disease (CHD). Subjects presenting lesions of
      endodontic origin (LEOs) or pulpal inflammation had an increased risk of
      developing CHD. However, findings concerning systemic manifestations of apical
      periodontitis (AP) remain controversial. An association between CD14 gene
      polymorphisms and atherosclerosis-associated diseases has been shown, but there
      are no data regarding an association between CD14 polymorphism and AP. This study
      evaluated associations between clinical oral health status, CD14 polymorphisms,
      and CHD. METHODS: A case-controlled clinical trial was designed to compare middle
      aged adults with acute myocardial infarction or unstable angina (n = 51) within
      12 months of the acute event defined as first manifestation with healthy controls
      (n = 49). Participants were matched for age, sex, and socioeconomic status.
      Indicators of oral disease and compliance were evaluated. CD14 polymorphisms were
      analyzed by restriction fragment length polymorphism-polymerase chain reaction.
      RESULTS: CHD subjects had a higher prevalence of oral diseases and lower
      compliance to oral preventive strategies than healthy controls. Multivariate
      analysis showed a positive association between missing teeth (odds ratio [OR] =
      1.37; 95% confidence interval [CI], 1.02-1.85), the number of LEOs (OR = 4.37;
      95% CI, 1.69-11.28), chronic periodontitis (OR = 5.87; 95% CI, 1.17-29.4), and
      CHD. No statistically significant association emerged between the CD14 C(-260)T
      and the CD14 C(-159)T polymorphism, endodontic or periodontal disease, and CHD.
      CONCLUSIONS: Chronic oral diseases may increase the risk of CHD and may be an
      unconventional risk factor for CHD.

PMID- 23146640
TI  - A prospective, randomized single-blind evaluation of effect of injection speed on
      anesthetic efficacy of inferior alveolar nerve block in patients with symptomatic
      irreversible pulpitis.
AB  - INTRODUCTION: Speed of injection may affect the solution spread in the
      pterygomandibular space. It was hypothesized that speed of injection will affect
      the anesthetic efficacy of inferior alveolar nerve block (IANB) in patients with
      symptomatic irreversible pulpitis. METHODS: Fifty-nine adult volunteers who were
      actively experiencing pain participated in this prospective, randomized, single
      blind study. The patients were divided into 2 groups on a random basis and
      received either slow or rapid IANB with 3.6 mL of 2% lidocaine with 1:200,000
      epinephrine. Endodontic access preparation was initiated after 15 minutes of the
      initial IANB. Pain during treatment was recorded by using the Heft-Parker visual
      analogue scale. The primary outcome measure, and the definition of success, was
      the ability to undertake pulp access and canal instrumentation with no or mild
      pain (Heft-Parker visual analog scale score < 55 mm). Secondary outcome measure
      was the solution deposition pain. Statistical analysis was performed by using
      Mann-Whitney U test and chi(2) test. RESULTS: Slow and rapid injections gave 43%
      and 51% success rates, respectively. The difference was statistically
      insignificant. Slow injections produced less solution deposition pain than rapid
      injections. CONCLUSIONS: Rate of injection has no effect on anesthetic success of
      IANB, but slow injections were more comfortable than rapid injections.

PMID- 23146641
TI  - Revascularization with and without platelet-rich plasma in nonvital, immature,
      anterior teeth: a pilot clinical study.
AB  - INTRODUCTION: This study was conducted to evaluate and compare maturogenesis
      induced by revascularization with and without platelet-rich plasma (PRP).
      METHODS: Twenty patients with nonvital, immature anterior teeth were randomly
      categorized into 2 groups. Subsequent to chemomechanical preparation,
      revascularization with and without PRP carried on a collagen sponge was induced
      in groups 1 and 2, respectively. The cases were followed up clinically and
      radiographically at 6- and 12-month intervals. RESULTS: Clinically, all cases
      were asymptomatic with complete resolution of signs and symptoms.
      Radiographically, there was a marked difference in periapical healing, apical
      closure, and dentinal wall thickening in group 2 in comparison with group 1.
      However, root lengthening was comparable for both of the procedures. CONCLUSIONS:
      Revascularization is a conservative and an effective method for inducing
      maturogenesis in nonvital, immature teeth. Supplementations with PRP can
      potentially improve the desired biological outcome of this regenerative
      technique.

PMID- 23146642
TI  - Evaluating the periapical status of teeth with irreversible pulpitis by using
      cone-beam computed tomography scanning and periapical radiographs.
AB  - INTRODUCTION: The purpose of this study was to compare the prevalence of apical
      periodontitis (AP) on individual roots of teeth with irreversible pulpitis viewed
      with periapical (PA) radiographs and cone-beam computed tomography (CBCT) scans.
      METHODS: PA radiographs and CBCT scans were taken of 138 teeth in 130 patients
      diagnosed with irreversible pulpitis (symptomatic and asymptomatic). Two
      calibrated examiners assessed the presence or absence of AP lesions by analyzing
      the PA and CBCT images. A consensus was reached in the event of any disagreement.
      The data were analyzed using the hypothesis test, and significance was set at P
      <= .05. RESULTS: Three hundred seven paired roots were assessed with both PA and
      CBCT images. A comparison of the 307 paired roots revealed that AP lesions were
      present in 10 (3.3%) and absent in 297 (96.7%) pairs of roots when assessed with
      PA radiography. When the same 307 sets of roots were assessed with CBCT scans, AP
      lesions were present in 42 (13.7%) and absent in 265 (86.3%) paired roots. The
      prevalence of AP lesions detected with CBCT was significantly higher in the
      symptomatic group compared with the asymptomatic group (P < .05). An additional
      22 roots were identified with CBCT alone. CONCLUSIONS: The present study
      highlights the advantages of using CBCT for detecting AP lesions, especially in
      teeth with symptomatic irreversible pulpitis.

PMID- 23146643
TI  - NLRP3 is expressed in human dental pulp cells and tissues.
AB  - INTRODUCTION: One of the best-characterized Nod-like receptor (NLR) family
      members is pyrin domain containing 3 (NLRP3). Intracellular NLRP3 is the most
      versatile innate immune receptor. On activation, NLRP3 assembles into a
      multiprotein complex, termed an inflammasome, which regulates the secretion and
      bioactivity of interleukin-1 family cytokines. NLRP3 has broad specificity for
      mediating an immune response to a wide range of microbial stimuli or danger
      signals. Therefore, we hypothesize that NLRP3 plays an essential role in the
      detection of bacterial pathogens and the initiation of inflammation within the
      dental pulp. Thus, the aim of this study was to evaluate the expression of NLRP3
      in normal human dental pulp cells (HDPCs) and pulp tissues. METHODS: Pulp tissues
      were collected from freshly extracted human third molars, and HDPCs were prepared
      from the explants of normal dental pulp tissues. Reverse transcription-polymerase
      chain reaction and Western blotting were performed to detect the levels of NLRP3
      mRNA and protein, respectively. In addition, immunohistochemical staining was
      used to determine the distribution of NLRP3 in pulp tissues. RESULTS: Normal
      human dental pulp tissues displayed high levels of NLRP3 mRNA and protein. NLRP3
      proteins were principally expressed in odontoblasts and some pulp vascular
      endothelial cells. Moreover, HDPCs also expressed NLRP3 but at a relatively low
      level in comparison with that of dental pulp tissues. CONCLUSIONS: The expression
      of NLRP3 in HDPCs and pulp tissues suggests that NLRP3-mediated signaling
      pathways may play an important role in dental immune defense.

PMID- 23146644
TI  - Lipopolysaccharide induces the migration of human dental pulp cells by up
      regulating miR-146a.
AB  - INTRODUCTION: MicroRNAs are small noncoding RNAs that play crucial roles in
      regulating normal and pathologic functions. Bacterial lipopolysaccharide (LPS) is
      one of the key regulators of pulpal pathogenesis. This study investigated how LPS
      regulates microRNA expression and affects the phenotype of human dental pulp
      cells (DPCs). METHODS: Primary DPCs were established and immortalized to achieve
      immortalized DPCs (I-DPCs). DPCs and I-DPCs were treated with LPS and examined to
      identify changes in microRNA expression, cell proliferation, and cell migration.
      Quantitative reverse-transcriptase polymerase chain reaction was used to detect
      changes in gene expression. Exogenous miR-146a expression was performed
      transfection with pre-mir-146a mimic. Knockdown of interleukin receptor
      associated kinase (IRAK1) and tumor necrosis factor receptor-associated factor 6
      (TRAF6) expression was performed by small interference oligonucleotide
      transfection. Western blot analysis was used to detect changes in the expression
      of the IRAK1 and TRAF6 proteins. RESULTS: The differentiation of DPCs was induced
      by osteogenic medium. I-DPCs had a higher level of human telomerase reverse
      transcriptase gene than the parental DPCs. Up-regulation of miR-146a expression
      and an increase in migration was induced by LPS treatment of DPCs and I-DPCs.
      Exogenous miR-146a expression increased the migration of DPCs and I-DPCs and down
      regulated the expression of IRAK1 and TRAF6. Knockdown of IRAK1 and/or TRAF6
      increased the migration of DPCs. CONCLUSIONS: The results suggested that LPS is
      able to increase the migration of DPCs by modulating the miR-146a-TRAF6/IRAK1
      regulatory cascade.

PMID- 23146645
TI  - Transplantation of dental pulp stem cells and platelet-rich plasma for pulp
      regeneration.
AB  - INTRODUCTION: The loss of dental pulp may weaken teeth, rendering them
      susceptible to reinfection, fracture, and subsequent tooth loss. Therefore,
      regeneration of pulp is considered an ideal treatment to preserve teeth. The aim
      of this study was to explore the capacity of dental pulp stem cells (DPSCs) and
      platelet-rich plasma (PRP) to regenerate dental pulp in canine mature permanent
      teeth. METHODS: Pulpectomy with apical foramen enlarged to a #80 file was
      performed in 16 upper premolars of 4 beagle dogs. Four experimental groups were
      randomly established: (1) the blood clot group, (2) the autologous DPSCs group,
      (3) the PRP group, and (4) the DP + PRP group (a mixture of DPSCs and PRP). Four
      lower premolars without any further treatment after pulpectomy were used as the
      control group. All teeth were sealed with mineral trioxide aggregate and
      composite. Twelve weeks after transplantation, the teeth were subjected to
      radiographic and histologic examination. RESULTS: Twenty-four of 32 experimental
      root canals gained newly formed tissues. All canals with an introduction of a
      blood clot showed histologic evidence of vital tissue formation. Cementum-like
      and periodontal ligament-like tissues along the internal root canal walls were
      typical structures in most cases. There is no significant difference between
      groups with or without autologous DPSC transplantation (exact chi-square test, P
      < .05). CONCLUSIONS: New vital tissues can be regenerated in permanent canine
      teeth after pulpectomy and enlargement of the apical foramen. Histologically,
      transplantation of DPSCs and/or PRP into root canals showed no enhancement in new
      tissue formation compared with inducement of a blood clot into the root canals
      alone.

PMID- 23146646
TI  - Occurrence of hypercementosis in a German population.
AB  - INTRODUCTION: The purpose of this study was to assess the occurrence of
      hypercementosis in a selected German dental school patient population. METHODS: A
      total of 800 full-mouth periapical radiographic series were screened. The
      radiographs were evaluated under optimal conditions by using double magnifying
      glasses. A total of 18,589 teeth including third molars were evaluated. The
      relative incidence of hypercementosis and the correlation regarding the location
      (left-side versus right-side occurrence, maxillary versus mandibular, and
      anterior versus posterior teeth) and between men and women were recorded and
      analyzed by using the chi(2) test. RESULTS: Eleven patients were found to have
      hypercementosis, 10 women and 1 man (P < .05). Of these, 5 of 11 (45.46%) had
      only 1 tooth with hypercementosis, and 6 had more than 1 (54.54%). In total, 22
      teeth associated with hypercementosis were found. Seven maxillary teeth were
      associated with hypercementosis (31.82%) and 15 mandibular teeth (68.18%) (P =
      .198). No significant differences were found regarding left-side and right-side
      occurrence of the affected teeth (P > .05). Hypercementosis was significantly
      more often associated with premolars and molars than with incisors (P < .01).
      Hypercementosis was found in 11 of 800 patients (1.33%). It was identified in 22
      of the 18,589 teeth examined (0.12%). CONCLUSIONS: The occurrence of
      hypercementosis among this selected German population was rare. Female patients
      were approximately 10 times more often affected than male patients. Mandibular
      teeth were approximately twice as often associated with hypercementosis as
      maxillary teeth.

PMID- 23146647
TI  - ProFile Vortex instruments after clinical use: a metallurgical properties study.
AB  - INTRODUCTION: The aim of the study was to analyze the incidence and mode of
      ProFile Vortex instrument (Dentsply Tulsa Dental Specialties, Tulsa, OK) defects
      during a predefined schedule of clinical use by the undergraduate students in a
      dental school setting and to examine the metallurgical characteristics of unused
      and clinically used Vortex instruments. METHODS: A total of 2,203 ProFile Vortex
      instruments discarded after single use from the undergraduate students program
      over 24 months were collected and examined for defects using a stereomicrosocpe
      at 10* magnification. The incidence and type of instrument defects or separation
      were analyzed. The lateral surfaces of part of the defected instruments and
      fracture surfaces of fractured files were examined using scanning electron
      microscopy. Unused and clinically used files were examined by differential
      scanning calorimetry and X-ray diffraction. Vickers hardness of the files was
      measured with a 200-g load. RESULTS: Only 1 of the 2,203 files fractured during
      clinical use. The cause of fracture was shear stress, and the file also showed
      unwinding of the helix structure. None of the remaining 2,202 files exhibited
      unwinding after clinical use. Blunt apicals were detected in 86 used files
      (3.9%). Austenite-finish temperatures were very similar for as-received, used
      files with defects and used files without defects, all exceeding 50 degrees C. No
      difference in microhardness was detected among these 3 instrument groups. X-ray
      diffraction results showed that NiTi files had austenite structure at room
      temperature. CONCLUSIONS: The risk of ProFile Vortex fracture is very low when
      files are used 1 time by undergraduate students. Unwinding of the files was not
      detected except for the fractured file. Clinical single use had no detectable
      effect on austenite-martensite phase transformation of the files. Unused and
      clinical single-use files contain a similar phase structure at body temperature.

PMID- 23146648
TI  - Shaping ability of three nickel-titanium endodontic file systems in simulated S
      shaped root canals.
AB  - INTRODUCTION: The purpose of this study was to determine the shaping ability of 3
      nickel-titanium (NiTi) endodontic file systems by measuring canal transportation.
      METHODS: Seventy-two S-shaped canals in resin blocks were randomly allocated into
      3 groups (n = 24): the Self-Adjusting File (SAF; ReDent Nova, Ra'anana, Israel)
      group, the Typhoon group (Typhoon rotary files with Controlled Memory Wire; DS
      Dental, Johnson City, TN), and the Vortex group (ProFile Vortex rotary files with
      M-Wire NiTi; Dentsply Tulsa Dental Specialties, Tulsa, OK). Blocks were secured
      in a jig for imaging standardization and instrumentation stabilization. Gates
      Glidden and PathFile drills (25 mm/.02 taper) were used to prepare the glide
      paths. For the Typhoon and Vortex groups (25 mm/.04 taper), canals were flooded
      with sterile water and instrumented using a crown-down technique from sizes 40 to
      20/.04 and then apically enlarged to size 30/.04. The SAF group (25 mm) was
      instrumented with constant sterile water irrigation in a light-pecking, transline
      motion. Pre- and postinstrumentation images were taken at 40* magnification and
      layered, and canal transportation was measured. RESULTS: After adjusting for the
      level and canal wall side, the mean transportation was significantly higher for
      the Typhoon (P < .001) and Vortex (P = .005) groups compared with the SAF group.
      Additionally, the mean transportation was significantly higher for the Typhoon
      group versus the Vortex group (P < .001). CONCLUSIONS: Under the conditions of
      this study, SAFs showed less canal transportation than ProFile Vortex and Typhoon
      files in simulated S-shaped root canals.

PMID- 23146649
TI  - Efficacy and safety of various active irrigation devices when used with either
      positive or negative pressure: an in vitro study.
AB  - INTRODUCTION: The purpose of this in vitro study was to evaluate and compare the
      efficacy and safety of different devices available for canal cleansing. METHODS:
      The following systems were tested: passive ultrasonic irrigation, EndoVac (Discus
      Dental, Culver City, CA), and the irrigation ultrasonic needle (ProUltra
      PiezoFlow Irrigation Ultrasonic Needle; Dentsply Tulsa Dental Specialties, Tulsa,
      OK) used in both the injection mode (IUNI) and the aspiration mode (IUNA). In the
      control group, traditional irrigation with a syringe and side-vented needle was
      used. A resin model was used with 4 lateral canals (respectively at 2, 5, 8, and
      11 mm from the apical foramen) filled with bovine pulp stained with fuchsin. The
      model also included a 2-mm chamber in communication with the apex, again filled
      with bovine pulp, which enabled the measurement of the extrusion of NaOCl beyond
      the apex. RESULTS: With regard to efficacy, the most effective systems were found
      to be those using the ultrasonic needle, either in aspiration or injection modes;
      EndoVac was the least effective. Conversely, IUNI was found to bring the highest
      risk with regard to the extrusion of sodium hypochlorite beyond the apex. EndoVac
      was the safest but only by a slight margin compared with IUNA and passive
      ultrasonic irrigation. CONCLUSIONS: Based on this study, the system that best
      reconciles efficacy and safety appears to be IUNA.

PMID- 23146650
TI  - Cytotoxicity of newly developed ortho MTA root-end filling materials.
AB  - INTRODUCTION: Various materials have been advocated for use as root-end filling
      materials. The purpose of the present in vitro study was to compare the
      cytotoxicity of 4 root-end filling materials: glass ionomer cement (GIC; Fuji II,
      GC Corp, Tokyo, Japan), reinforced zinc oxide-eugenol cement (IRM; Dentsply Tulsa
      Dental, Tulsa, OK), and 2 types of mineral trioxide aggregate. METHODS: This
      study used MG-63 cells derived from a human osteosarcoma. To quantitatively
      evaluate the cytotoxicity of test materials, the 2,3-bis-(2-methoxy-4-nitro-5
      sulfophenyl)-2H-tetrazolium-5-carboxanilide (XTT) assay was used. The cells were
      exposed to the extracts and incubated. Cell viability was recorded by measuring
      the optical density of each test well in reference to controls. Each specimen was
      examined by scanning electron microscopy for the observation of cell morphology.
      RESULTS: The XTT assay showed that the cell viability of ProRoot MTA (Dentsply
      Tulsa Dental) was higher than that of GIC and Ortho MTA (BioMTA, Seoul, Republic
      of Korea) at all time points. IRM showed significantly lower cell viability than
      the other groups. The scanning electron microscopic analysis revealed that
      elongated, dense, and almost confluent cells were observed in the cultures of
      GIC, Ortho MTA, and ProRoot MTA specimens. In contrast, cells on the surface of
      IRM were rounded in shape, and the numbers and the density of the cells were
      smaller than that in the other groups. CONCLUSIONS: ProRoot MTA and GIC showed
      good biocompatibility in this study. However, Ortho MTA showed lower
      biocompatibility compared with ProRoot MTA and GIC.

PMID- 23146651
TI  - Canal and isthmus debridement efficacy of the VPro EndoSafe negative-pressure
      irrigation technique.
AB  - INTRODUCTION: This study compared canal and isthmus debridement efficacies
      between side-vented needle irrigation (SNI) and the VPro EndoSafe (VPro) negative
      pressure device (Vista Dental, Racine, WI) in mesial roots of mandibular first
      molars with narrow isthmuses in a closed-canal design. METHODS: Twenty teeth with
      narrow isthmuses were selected using micro-computed tomography scanning. Collagen
      solution was reconstituted with 1% NH(4)OH to simulate debris and injected into
      canals via vacuum. Canals were instrumented to size 40/.04. Final irrigation was
      performed with 17% EDTA and 6% NaOCl using SNI with a 30-G needle or the VPro
      system. Roots were demineralized, and Masson trichrome-stained sections were
      prepared at 1.2 to 3.2 mm from the anatomic apex for a total of 6 canal levels.
      Debris-filled areas within the canals and isthmuses were measured using ImageJ
      software (National Institutes of Health, Bethesda, MD) and statistically analyzed
      using repeated-measures analysis. RESULTS: There was no significant difference
      between techniques and debridement efficacy among the 6 levels within the canal
      (P = .108). The debridement efficacy at 1.6 mm differed significantly from that
      at 3.2 mm. VPro had significantly more debris at isthmus levels 2.0 and 2.4 mm
      than SNI (P = .009). A significant difference was observed between the canal and
      the isthmus (P < .001). Neither VPro nor SNI removed debris completely from the
      apical third or isthmus. CONCLUSIONS: VPro EndoSafe did not differ significantly
      from SNI in the overall debridement efficacy in the apical third of mesial roots
      of mandibular first molars.

PMID- 23146652
TI  - Does the geometric location of odontoblast differentiation and dentinal tubules
      depend on a reaction-diffusion system between BMP2 and Noggin? A mathematical
      model.
AB  - INTRODUCTION: The mesenchymal differentiation to odontoblasts is a complex
      process that determines the formation of dentinal tubules. This process involves
      a carefully regulated sequence of changes in the behavior of mesenchymal cells
      coordinated by the expression of different molecular factors that includes mainly
      the Noggin and bone morphogenetic protein type 2 (BMP2). METHODS: We investigated
      a bioregulatory mathematic model based on a set of equations of reaction
      diffusion to predict the geometry of the formation of the dentinal tubules.
      RESULTS: We found that odontoblast location and the dentinal tubules formation
      are determined by the spatial distribution of a set of molecular signals that
      compete among themselves to maintain places of the greatest concentration of
      BMP2, which determines the step from mesenchymal cells to odontoblasts and the
      formation of the dentinal tubules. CONCLUSIONS: This mathematic model suggests a
      regulatory loop between BMP2 and Noggin, which is highly stable and repeatable
      and determines the right location patterns of the odontoblasts and the formation
      of dentinal tubules. This mathematic approach allows us to understand biological
      phenomena and biochemical activity during the period of pulp differentiation.

PMID- 23146653
TI  - Multiple radiopaque mandibular lesions in a patient with Apert syndrome.
AB  - INTRODUCTION: Apert syndrome (acrocephalosyndactyly) is a rare congenital
      malformation characterized by craniosynostosis, craniofacial anomalies, and
      symmetric syndactyly of the hands and feet. Oral manifestations usually include
      bifid uvula, a Byzantine arch palate associated with lateral swellings of the
      palatine processes, severe maxillary dental crowding associated with teeth
      malposition, severe open bite, dental caries, and gingival and periodontal
      disorders. Florid osseous dysplasia is an asymptomatic lesion mostly encountered
      during casual dental radiographic examinations as multiple sclerotic masses in 2
      or more quadrants, usually in tooth-bearing regions. METHODS: A 32-year-old woman
      diagnosed with Apert syndrome was seen in our department for a routine dental
      examination. Radiographic evaluation showed multiple radiopaque lesions in the
      mandible. All teeth with radiopaque lesions gave positive responses to vitality
      tests, and the patient did not report any symptoms. Based on the clinical and
      radiographic findings, the diagnosis of florid osseous dysplasia in a patient
      with Apert syndrome was made. Because there were no signs of an intraoral
      infectious process or endodontic needs, the patient was followed during revisions
      for Apert syndrome, and the only treatment provided was conservative management
      of the many carious lesions observed during the clinical examination.
      CONCLUSIONS: To our knowledge, this is the first study reporting the occurrence
      of florid osseous dysplasia in a patient with Apert syndrome. Conservative
      management should be performed in asymptomatic cases. Although rare, our case
      report highlights the importance of florid osseous dysplasia as a condition that
      may mimic lesions with an endodontic origin in patients with Apert syndrome.

PMID- 23146654
TI  - Sepsis-induced morbidity in mice: effects on body temperature, body weight, cage
      activity, social behavior and cytokines in brain.
AB  - Infection negatively impacts mental health, as evidenced by the lethargy,
      malaise, and cognitive deficits experienced during illness. These changes in
      central nervous system processes, collectively termed sickness behavior, have
      been shown in animal models to be mediated primarily by the actions of cytokines
      in brain. Most studies of sickness behavior to date have used bolus injection of
      bacterial lipopolysaccharide (LPS) or selective administration of the
      proinflammatory cytokines interleukin-1beta (IL-1beta) or IL-6 as the immune
      challenge. Such models, although useful for determining mechanisms responsible
      for acute changes in physiology and behavior, do not adequately represent the
      more complex effects on central nervous system (CNS) processes of a true
      infection with replicating pathogens. In the present study, we used the cecal
      ligation and puncture (CLP) model to quantify sepsis-induced alterations in
      several facets of physiology and behavior of mice. We determined the impact of
      sepsis on cage activity, body temperature, food and water consumption and body
      weights of mice. Because cytokines are critical mediators of changes in behavior
      and temperature regulation during immune challenge, we also quantified sepsis
      induced alterations in cytokine mRNA and protein in brain during the acute period
      of sepsis onset. We now report that cage activity and temperature regulation in
      mice that survive are altered for up to 23 days after sepsis induction. Food and
      water consumption are transiently reduced, and body weight is lost during sepsis.
      Furthermore, sepsis decreases social interactions for 24-48 h. Finally, mRNA and
      protein for IL-1beta, IL-6, and tumor necrosis factor-alpha (TNFalpha) are
      upregulated in the hypothalamus, hippocampus, and brain stem during sepsis onset,
      from 6h to 72 h post sepsis induction. Collectively, these data indicate that
      sepsis not only acutely alters physiology, behavior and cytokine profiles in
      brain, but that some brain functions are impaired for long periods in animals
      that survive.

PMID- 23146656
TI  - Glucocorticoid treatment increases density of serotonin 5-HT2A receptors in
      humans.
AB  - BACKGROUND: Interactions between the serotonergic system and the hypothalamic
      pituitary-adrenal axis have been suggested, albeit the details for such
      interactions have yet to be established. Animal studies have shown that the
      density of serotonin 5-HT2A receptors is increased after administration of
      exogenous glucocorticoids. OBJECTIVE: The objective of this study was to explore
      possible changes in the pattern of density and affinity of 5-HT2A receptors in
      humans after treatment with glucocorticoids. METHODS: Using a radioactive binding
      assay, the density and affinity (measured as Bmax and Kd) of 5-HT2A serotonin
      receptors were measured in blood samples drawn from 27 individuals diagnosed with
      polymyalgia rheumatica and/or giant cell arteritis before and after start of an
      oral treatment with prednisolone. For each patient Bmax and Kd at baseline before
      prednisolone treatment were compared with Bmax and Kd in samples drawn at a first
      and second follow-up clinic visit at an average of 8.8 (+/-2.5) days and 33.6 (+/
      6.8) days, respectively. RESULTS: The density of 5-HT2A receptors increased after
      treatment in 23 individuals. The mean Bmax value at baseline for all patients was
      45.2 fmol/mg protein compared with 64.9 fmol/mg protein in the corresponding
      samples drawn at the second follow-up visit (p=0.001). There also was an
      association between individuals accumulated prednisolone dose and the magnitude
      of change in Bmax between baseline and the first follow-up visit. Erythrocyte
      sedimentation rate, platelet count or gender had no influence on the results.
      There were no significant differences in Kd during the treatment period. However,
      a low Kd value at baseline was a predictor for an increase in Bmax following
      treatment. CONCLUSIONS: The results of this study showed that the density of 5
      HT2A serotonin receptors in man is increased after a subchronic treatment with
      glucocorticoids. The magnitude of the increase appears to be associated with the
      affinity of 5-HT2A receptors before treatment and the accumulated dose of
      glucocorticoid early in the treatment period.

PMID- 23146655
TI  - Examining the association between salivary cortisol levels and subclinical
      measures of atherosclerosis: the Multi-Ethnic Study of Atherosclerosis.
AB  - OBJECTIVE: To investigate the association between salivary cortisol and two
      markers of subclinical cardiovascular disease (CVD), coronary calcification
      (CAC), and ankle-brachial index (ABI). METHODS: Data from an ancillary study to
      the Multi-Ethnic Study of Atherosclerosis (MESA), the MESA Stress Study, were
      used to analyze associations of salivary cortisol data collected six times per
      day over three days with CAC and ABI. The authors used mixed models with repeat
      cortisol measures nested within persons to determine if specific features of the
      cortisol profile were associated with CAC and ABI. RESULTS: A total of 464
      participants were included in the CAC analysis and 610 in the ABI analysis. The
      mean age of participants was 65.6 years. A 1-unit increase in log coronary
      calcium was associated with a 1.77% flatter early decline in cortisol (95% CI:
      0.23, 3.34) among men and women combined. Among women low ABI was associated with
      a steeper early decline (-13.95% CI: -25.58, -3.39) and a marginally
      statistically significant flatter late decline (1.39% CI: -0.009, 2.81). The
      cortisol area under the curve and wake to bedtime slope were not associated with
      subclinical CVD. CONCLUSIONS: This study provides weak support for the link
      between cortisol and measures of subclinical atherosclerosis. We found an
      association between some features of the diurnal cortisol profile and coronary
      calcification and ABI but associations were not consistent across subclinical
      measures. There are methodological challenges in detecting associations of
      cortisol measures at a point in time with health outcomes that develop over a
      lifetime. Studies of short-term mechanisms linking stress to physiological
      processes related to the development of early atherosclerosis may be more
      informative.

PMID- 23146658
TI  - Single atom microscopy.
AB  - We show that aberration-corrected scanning transmission electron microscopy
      operating at low accelerating voltages is able to analyze, simultaneously and
      with single atom resolution and sensitivity, the local atomic configuration,
      chemical identities, and optical response at point defect sites in monolayer
      graphene. Sequential fast-scan annular dark-field (ADF) imaging provides direct
      visualization of point defect diffusion within the graphene lattice, with all
      atoms clearly resolved and identified via quantitative image analysis. Summing
      multiple ADF frames of stationary defects produce images with minimized
      statistical noise and reduced distortions of atomic positions. Electron energy
      loss spectrum imaging of single atoms allows the delocalization of inelastic
      scattering to be quantified, and full quantum mechanical calculations are able to
      describe the delocalization effect with good accuracy. These capabilities open
      new opportunities to probe the defect structure, defect dynamics, and local
      optical properties in 2D materials with single atom sensitivity.

PMID- 23146657
TI  - Comparison of mastoscopic and conventional axillary lymph node dissection in
      breast cancer: long-term results from a randomized, multicenter trial.
AB  - OBJECTIVE: To compare the long-term results of mastoscopic axillary lymph node
      dissection (MALND) and conventional axillary lymph node dissection (CALND).
      PATIENTS AND METHODS: From January 1, 2003, through December 31, 2005, a group of
      1027 consecutive patients with operable breast cancer were randomly assigned to 1
      of 2 study groups: MALND and CALND. The median follow-up was 63 months. The
      primary end points of the study were operative outcomes, complication reduction,
      function conservation, and cosmetics. The secondary end points were disease-free
      and overall survival. RESULTS: The mean operative blood loss in the MALND group
      was less than in the CALND group (P<.001). The patients who underwent MALND had
      less axillary pain, numbness or paresthesias, and arm swelling (P<.001). The
      aesthetic appearance of the axilla in the MALND group was much better than that
      in the CALND group (P=.001 at 6 months and P=.002 at 24 months). A significant
      difference was found between the 2 groups in distant metastasis (P=.04). The
      disease-free survival rate was 64.5% in the MALND group and 60.8% in the CALND
      group (P=.88). The overall survival rate was 81.7% in the MALND group and 78.6%
      in the CALND group (P=.95). CONCLUSION: Compared with CALND, MALND has advantages
      in operative outcomes, complication reduction, function conservation, and
      cosmetics.

PMID- 23146659
TI  - Subclinical deterioration of systolic right ventricular function parameters in
      adolescents with mild cystic fibrosis.

PMID- 23146660
TI  - Infliximab reduces CD147, MMP-3, and MMP-9 expression in peripheral blood
      monocytes in patients with active rheumatoid arthritis.
AB  - Recent studies have reported elevated expression levels in active rheumatoid
      arthritis patients of the cluster of differentiation (CD) 147 on CD14(+)
      peripheral blood monocytes and as a result, CD147 may be a target for the
      development of a novel rheumatoid arthritis therapy. This report describes the
      inhibitory effects of infliximab on CD147 and metalloproteinases (MMP)-3 and MMP
      9 overexpression in peripheral blood monocytes obtained from patients with active
      rheumatoid arthritis. Thirty patients with active rheumatoid arthritis that were
      refractory to methotrexate therapy were randomized at a 4:1 ratio into groups A
      and B, respectively. Group A received three to four infusions of infliximab
      (3mg/kg) and group B participants received four infusions of placebo. Both groups
      were also treated with a stable background dose of methotrexate. The CD147
      expression levels on CD14(+) peripheral blood monocytes of rheumatoid arthritis
      patients was detected by flow cytometry. The expression of CD147, MMP-3, and, MMP
      9 mRNA in peripheral blood mononuclear cells was assayed by real-time
      quantitative PCR, and the expression of MMP-3 and MMP-9 in serum was measured by
      a multiplexed microsphere-based flow assay. Results showed that the expression of
      CD147 and MMP-9 mRNA in group A decreased compared to group B. Expression of
      CD147 on CD14(+) monocytes was reduced (P<0.05), and serum MMP-3 and -9 levels in
      group A were decreased by week 18. These data suggested that infliximab could
      inhibit CD147 expression on CD14(+) monocytes as well as reduce the levels of MMP
      3 and MMP-9 in peripheral blood monocytes.

PMID- 23146661
TI  - Vitamin K deficiency bleeding: overview and considerations.

PMID- 23146662
TI  - Comparison of transcriptional response to phorbol ester, bryostatin 1, and
      bryostatin analogs in LNCaP and U937 cancer cell lines provides insight into
      their differential mechanism of action.
AB  - Bryostatin 1, like the phorbol esters, binds to and activates protein kinase C
      (PKC) but paradoxically antagonizes many but not all phorbol ester responses.
      Previously, we have compared patterns of biological response to bryostatin 1,
      phorbol ester, and the bryostatin 1 derivative Merle 23 in two human cancer cell
      lines, LNCaP and U937. Bryostatin 1 fails to induce a typical phorbol ester
      biological response in either cell line, whereas Merle 23 resembles phorbol ester
      in the U937 cells and bryostatin 1 in the LNCaP cells. Here, we have compared the
      pattern of their transcriptional response in both cell lines. We examined by qPCR
      the transcriptional response as a function of dose and time for a series of genes
      regulated by PKCs. In both cell lines bryostatin 1 differed primarily from
      phorbol ester in having a shorter duration of transcriptional modulation. This
      was not due to bryostatin 1 instability, since bryostatin 1 suppressed the
      phorbol ester response. In both cell lines Merle 23 induced a pattern of
      transcription largely like that of phorbol ester although with a modest reduction
      at later times in the LNCaP cells, suggesting that the difference in biological
      response of the two cell lines to Merle 23 lies downstream of this
      transcriptional regulation. For a series of bryostatins and analogs which ranged
      from bryostatin 1-like to phorbol ester-like in activity on the U937 cells, the
      duration of transcriptional response correlated with the pattern of biological
      activity, suggesting that this may provide a robust platform for structure
      activity analysis.

PMID- 23146663
TI  - P2Y purinergic receptors: new targets for analgesic and antimigraine drugs.
AB  - Millions of individuals worldwide suffer from acute and, more severely, chronic
      pain conditions (e.g., neuropathic pain, and migraine). The latter bear
      tremendous personal, familial, and social costs, since sufferers and their
      relatives undergo a complete turnaround of their lives with the search of relief
      from pain becoming their pivotal thought. Sadly, to date no effective
      pharmacological approaches are available which can alleviate chronic pain
      significantly or in the long run in all patients. The current central strategy
      for the development of new and effective painkillers lies in the hypothesis that
      cellular and/or molecular players in nociception must exists that are not
      targeted by "classical" analgesics, and therefore researchers have put tremendous
      efforts into the in-depth analysis of the pathways leading to pain development
      and maintenance over time. In this complex scenario, two outsiders are now taking
      the center stage: glial cells in sensory ganglia and in the central nervous
      system, thanks to their ability to communicate with neurons and to modulate their
      firing, and the purinergic system. Extracellular purine and pyrimidine
      nucleotides are involved in the physiology of virtually every body district, and
      their extracellular concentrations massively increase under pathological
      situations, suggesting that they might represent potential targets for the
      modulation of disease-associated symptoms, like pain. Here, we provide an
      overview of the present knowledge of the role of nucleotides in nociception, with
      a particular emphasis on G protein-coupled P2Y receptors and their involvement in
      the communication between first- and second-order neurons in sensory nerve
      pathways and surrounding glial cells.

PMID- 23146664
TI  - Mesalamine modulates intercellular adhesion through inhibition of p-21 activated
      kinase-1.
AB  - Mesalamine (5-ASA) is widely used for the treatment of ulcerative colitis, a
      remitting condition characterized by chronic inflammation of the colon. Knowledge
      about the molecular and cellular targets of 5-ASA is limited and a clear
      understanding of its activity in intestinal homeostasis and interference with
      neoplastic progression is lacking. We sought to identify molecular pathways
      interfered by 5-ASA, using CRC cell lines with different genetic background.
      Microarray was performed for gene expression profile of 5-ASA-treated and
      untreated cells (HCT116 and HT29). Filtering and analysis of data identified
      three oncogenic pathways interfered by 5-ASA: MAPK/ERK pathway, cell adhesion and
      beta-catenin/Wnt signaling. PAK1 emerged as a consensus target of 5-ASA,
      orchestrating these pathways. We further investigated the effect of 5-ASA on cell
      adhesion. 5-ASA increased cell adhesion which was measured by cell adhesion assay
      and transcellular-resistance measurement. Moreover, 5-ASA treatment restored
      membranous expression of adhesion molecules E-cadherin and beta-catenin. Role of
      PAK1 as a mediator of mesalamine activity was validated in vitro and in vivo.
      Inhibition of PAK1 by RNA interference also increased cell adhesion. PAK1
      expression was elevated in APC(min) polyps and 5-ASA treatment reduced its
      expression. Our data demonstrates novel pharmacological mechanism of mesalamine
      in modulation of cell adhesion and role of PAK1 in APC(min) polyposis. We propose
      that inhibition of PAK1 expression by 5-ASA can impede with neoplastic
      progression in colorectal carcinogenesis. The mechanism of PAK1 inhibition and
      induction of membranous translocation of adhesion proteins by 5-ASA might be
      independent of its known anti-inflammatory action.

PMID- 23146665
TI  - CMV antigenemia and quantitative viral load assessments in hematopoietic stem
      cell transplant recipients.
AB  - BACKGROUND: Sensitive and reliable diagnostic tests are essential for the
      prevention of cytomegalovirus (CMV) disease after hematopoietic stem cell
      transplantation (HSCT). pp65 antigenemia and polymerase chain reaction (PCR)
      assays are commonly used to monitor CMV in HSCT recipients. However, there is
      considerable intra- and inter-laboratory variability in the results, which impact
      comparability and clinical practice. OBJECTIVES/STUDY DESIGN: Using 380 samples
      from 135 HSCT recipients, we compared the new FDA approved quantitative PCR
      assay, COBAS((r)) AmpliPrep/COBAS((r)) TaqMan((r)) CMV test (CAP/CTM CMV test)
      developed and standardized using the 1st WHO International Standard for CMV with
      pp65 antigenemia and COBAS((r)) AMPLICOR MONITOR CMV tests. RESULTS: The median
      time between transplantation and testing samples was 57 days (range, 0-207 days).
      The median CMV load (log(10)) was 3.17 IU/mL (3.21 copies/mL). Among samples with
      detectable CMV load, 52% were negative by pp65 antigenemia. CMV loads were higher
      in pp65 antigenemia-positive than in negative samples. One pp65-antigenemia
      positive cell per 100,000 leukocytes corresponded to a median CMV load of 1200
      IU/mL. CMV loads determined by the CAP/CTM CMV test were slightly lower than the
      ones by the AMPLICOR MONITOR CMV test (-0.15 [95% CI, -0.18 to -0.13] copies/mL),
      but slope differences indicated only limited co-linearity. CONCLUSIONS: The
      CAP/CTM CMV test is more sensitive than pp65 antigenemia and the AMPLICOR MONITOR
      CMV test in HSCT recipients. The lower limit of quantification and co-linearity
      with the international WHO standard renders the CAP/CTM CMV test suitable for
      future clinical trials defining viral load thresholds of CMV therapy.

PMID- 23146667
TI  - Organochlorine pesticides in the lower reaches of Yangtze River: occurrence,
      ecological risk and temporal trends.
AB  - Residues of 24 organochlorine pesticides (OCPs) including DDT metabolites were
      investigated in the water and surface sediments from the lower reaches of the
      Yangtze River to evaluate their pollution and potential risks. Concentrations of
      OCP residues (SigmaOCP24 ranged from 3.07 to 23.70 ng/L in water and 0.67 to
      58.80 ng/g dw in sediments) were generally within safe levels, while adverse
      biological effects are likely from DDT pollution in the lower reaches. HCH and
      DDT residues dominated the OCPs. High detection rates but low concentrations of
      some other OCPs, such as chlordane and endosulfan, were detected in both water
      and sediments. The HCH and DDT residues in the lower reaches primarily originated
      from historical use of technical HCH and DDT, although additional sources of
      lindane and dicofol existed in the region. Temporal trends of pesticide
      contamination levels indicated that HCH concentrations have decreased over the
      past decades. However, there was no obvious trend of declining DDT concentrations
      in the sediments from the Yangtze River. The DDT metabolites, DDMU (bis
      (chlorophenyl)-1-chloroethylene), DBP (dichlorobenzophenone) and DDM (bis
      (chlorophenyl) methane), were also investigated for the first time in water and
      sediments from the Yangtze River.

PMID- 23146666
TI  - JAK-STAT1/3-induced expression of signal sequence-encoding proopiomelanocortin
      mRNA in lymphocytes reduces inflammatory pain in rats.
AB  - BACKGROUND: Proopiomelanocortin (POMC)-derived beta-endorphin1-31 from immune
      cells can inhibit inflammatory pain. Here we investigated cytokine signaling
      pathways regulating POMC gene expression and beta-endorphin production in
      lymphocytes to augment such analgesic effects. RESULTS: Interleukin-4 dose
      dependently elevated POMC mRNA expression in naive lymph node-derived cells in
      vitro, as determined by real-time PCR. This effect was neutralized by janus
      kinase (JAK) inhibitors. Transfection of Signal Transducer and Activator of
      Transcription (STAT) 1/3 but not of STAT6 decoy oligonucleotides abolished
      interleukin-4 induced POMC gene expression. STAT3 was phosphorylated in in vitro
      interleukin-4 stimulated lymphocytes and in lymph nodes draining inflamed paws in
      vivo. Cellular beta-endorphin increased after combined stimulation with
      interleukin-4 and concanavalin A. Consistently, in vivo reduction of inflammatory
      pain by passively transferred T cells improved significantly when donor cells
      were pretreated with interleukin-4 plus concanavalin A. This effect was blocked
      by naloxone-methiodide. CONCLUSION: Interleukin-4 can amplify endogenous opioid
      peptide expression mediated by JAK-STAT1/3 activation in mitogen-activated
      lymphocytes. Transfer of these cells leads to inhibition of inflammatory pain via
      activation of peripheral opioid receptors.

PMID- 23146668
TI  - Differential gene expression in Iberian green frogs (Pelophylax perezi)
      inhabiting a deactivated uranium mine.
AB  - Iberian green frogs (Pelophylax perezi) were found inhabiting a deactivated
      uranium mine, especially an effluent pond, seriously contaminated with metals and
      radionuclides. These animals were previously assessed for oxidative stress
      parameters and did not revealed significant alterations. In order to better
      understand which mechanisms may be involved in the ability to withstand permanent
      contamination gene expression analysis was performed in the liver, through
      suppression subtractive hybridization (SSH). The SSH outcome in the liver
      revealed the up-regulation of genes coding for the ribosomal protein L7a and for
      several proteins typical from blood plasma: fibrinogen, hemoglobin and albumin.
      Besides their normal function, some of these proteins can play an important role
      as protective agents against oxidative stress. This work provides new insights on
      possible basal protection mechanisms that may act in organisms exposed
      chronically to contamination.

PMID- 23146669
TI  - Exposure to silver nanoparticles does not affect cognitive outcome or hippocampal
      neurogenesis in adult mice.
AB  - Due to the unique antimicrobial and many other broad spectrum biotechnological
      advantages, silver nanoparticles (Ag-NPs) are widely used in biomedical and
      general applications. However, the current knowledge about the impact of Ag-NPs
      on the central nervous system is extremely limited. To assess whether Ag-NPs
      influence spatial cognition and adult hippocampal neurogenesis, male ICR mice
      received intraperitoneal administration of Ag-NPs (10, 25, and 50 mg/kg body
      weight) or vehicle every day for 7 days. At the end of this time period, Morris
      water maze test was performed for the spatial learning and memory. Subsequently,
      mice were injected with bromodeoxyuridine and sacrificed 1 day or 28 days after
      the last injection in order to evaluate cell proliferation, survival and
      differentiation in the hippocampus. Results showed that compared with the control
      group, both reference memory and working memory were not impaired in Ag-NPs
      exposed groups. In addition, no differences were observed in hippocampal
      progenitor proliferation, new born cell survival or differentiation. These data
      reveal that exposure to Ag-NPs does not affect spatial cognition or hippocampal
      neurogenesis in mice.

PMID- 23146670
TI  - Decrease of p400 ATPase complex and loss of H2A.Z within the p21 promoter occur
      in senescent IMR-90 human fibroblasts.
AB  - Replicative senescence in human diploid fibroblasts is characterised by an
      exhaustion of proliferative potential and permanent cell cycle arrest. During
      senescence, telomere shortening-generated DNA damage activates p53 pathway that
      upregulates cell cycle inhibitors, such as p21. Human p400 ATPase is a chromatin
      remodeller that plays a key role in the deposition of the histone variant, H2A.Z
      within the p21 promoter, repressing p21 gene expression. Decline of p400 ATPase
      in senescent IMR-90 cells prompted us to investigate structural changes in the
      chromatin of the p21 promoter during in vitro aging. Whereas doxorubicin
      treatment in early-passaged cells results in nucleosome density changes near the
      p53 binding sites of the p21 promoter, our studies show that senescent cells with
      a high p21 transcription activity had a comparable nucleosome distribution as
      unstressed young cells. However, H2A.Z that is highly enriched within the p21
      promoter of young cells is depleted in senescent cells, suggesting that
      downregulation of p400 and loss of H2A.Z localisation play roles in relieving p21
      gene repression in senescent IMR-90 cells. Taken together, our results indicate
      that age-dependent p400 downregulation and loss of H2A.Z localisation may
      contribute to the onset of replicative senescence through a sustained high rate
      of p21 transcription.

PMID- 23146671
TI  - Blue-green algae or cyanobacteria in the intestinal micro-flora may produce
      neurotoxins such as Beta-N-Methylamino-L-Alanine (BMAA) which may be related to
      development of amyotrophic lateral sclerosis, Alzheimer's disease and Parkinson
      Dementia-Complex in humans and Equine Motor Neuron Disease in horses.

PMID- 23146672
TI  - The important role of microRNAs in lipid metabolism.

PMID- 23146673
TI  - A full-length recombinant Plasmodium falciparum PfRH5 protein induces inhibitory
      antibodies that are effective across common PfRH5 genetic variants.
AB  - The lack of an effective licensed vaccine remains one of the most significant
      gaps in the portfolio of tools being developed to eliminate Plasmodium falciparum
      malaria. Vaccines targeting erythrocyte invasion - an essential step for both
      parasite development and malaria pathogenesis - have faced the particular
      challenge of genetic diversity. Immunity-driven balancing selection pressure on
      parasite invasion proteins often results in the presence of multiple,
      antigenically distinct, variants within a population, leading to variant-specific
      immune responses. Such variation makes it difficult to design a vaccine that
      covers the full range of diversity, and could potentially facilitate the
      evolution of vaccine-resistant parasite strains. In this study, we investigate
      the effect of genetic diversity on invasion inhibition by antibodies to a high
      priority P. falciparum invasion candidate antigen, P. falciparum Reticulocyte
      Binding Protein Homologue 5 (PfRH5). Previous work has shown that virally
      delivered PfRH5 can induce antibodies that protect against a wide range of
      genetic variants. Here, we show that a full-length recombinant PfRH5 protein
      expressed in mammalian cells is biochemically active, as judged by saturable
      binding to its receptor, basigin, and is able to induce antibodies that strongly
      inhibit P. falciparum growth and invasion. Whole genome sequencing of 290
      clinical P. falciparum isolates from across the world identifies only five non
      synonymous PfRH5 SNPs that are present at frequencies of 10% or more in at least
      one geographical region. Antibodies raised against the 3D7 variant of PfRH5 were
      able to inhibit nine different P. falciparum strains, which between them included
      all of the five most common PfRH5 SNPs in this dataset, with no evidence for
      strain-specific immunity. We conclude that protein-based PfRH5 vaccines are an
      urgent priority for human efficacy trials.

PMID- 23146674
TI  - Sustained high influenza vaccination rates and decreased safety concerns among
      pregnant women during the 2010-2011 influenza season.
AB  - OBJECTIVE: Intense efforts to vaccinate pregnant women against 2009 H1N1
      influenza resulted in much higher vaccine uptake than previously reported. We
      surveyed postpartum women to determine whether high vaccination rates were
      sustained during the 2010-11 influenza season. METHODS: We performed cross
      sectional surveys of postpartum women delivering at our institution during
      February-April 2010 and February-March 2011. The surveys ascertained maternal
      characteristics, history of influenza vaccination, and reasons for lack of
      vaccination. RESULTS: During the 2010-11 season, 165 (55%) of 300 women surveyed
      reported receiving influenza vaccination, compared to 191 of 307 (62%) during
      2009-10 (p=0.08). Vaccination by an obstetrical provider was common, but
      decreased compared to 2009-10 (60% vs. 71%, p=0.04). While most women (76%) in
      2010-11 reported that their provider recommended influenza vaccination,
      significantly more reported lack of discussion about vaccination (24% vs. 11%,
      p<0.01) compared to 2009-10. Vaccine safety concerns were cited by most (66%)
      women declining vaccination during 2009-10 but only 27% of women who declined in
      2010-11. CONCLUSION: The vaccination rate among pregnant women at our institution
      was relatively sustained, although fewer providers appear to be discussing
      influenza vaccination in pregnancy. Concern about vaccine safety, the primary
      barrier during 2009-10, was much less prominent.

PMID- 23146675
TI  - Prevalence, incidence and persistence of genital HPV infections in a large cohort
      of sexually active young women in the Netherlands.
AB  - BACKGROUND: We assessed age- and type-specific HPV prevalence, incidence and
      persistence and their associated risk factors in young women prior to
      vaccination, to enable monitoring of the impact of introduction of HPV
      vaccination in the years before participation in the cervical screening program.
      METHODS: The HPV status was assessed in 3282 women aged 16-29 who participated in
      a Chlamydia trachomatis screening implementation program, of which 2014 women
      (61%) participated in two rounds (one year apart). Self-collected vaginal swab
      were analyzed by SPF(10) LiPA on the presence of HPV DNA. Risk factors for
      prevalent, incident and persistent HPV infections were calculated using
      generalized estimating equation. RESULTS: The prevalence of any HPV in the first
      round amounted to 54%, while 34% of the women who participated in the second
      round had a persistent infection and 45% an incident infection. The five most
      common HPV types found in this study were HPV16, -51, -52, -31 and -53. HPV16
      and/or HPV18 prevalence, incidence and persistence in the second round were 15%,
      8% and 9%, respectively and for HPV6 and/or HPV11 6%, 4% and 2%, respectively.
      Relatively to other HPV genotypes, hrHPV types were found more often as a
      persistent infection than as an incident infection. Furthermore, there is an age
      dependent increase within this age range for persistent infections but not for
      incident infections. CONCLUSION: The HPV prevalence (54%), incidence (45%) and
      persistence (34%) is high among sexually active young women in the Netherlands.
      The different HPV type distribution and risk factors for prevalent, incident and
      persistent infections, as well as the observed age-trends should be taken into
      account in interpreting data obtained after vaccine introduction. Repeating
      measurements post-immunization are particularly relevant until the age when
      screening starts (i.e. 30 years in the Netherlands).

PMID- 23146676
TI  - Comparative cost models of a liquid nitrogen vapor phase (LNVP) cold chain
      distributed cryopreserved malaria vaccine vs. a conventional vaccine.
AB  - Typically, vaccines distributed through the Expanded Program on Immunization
      (EPI) use a 2-8 degrees C cold chain with 4-5 stops. The PfSPZ Vaccine comprises
      whole live-attenuated cryopreserved sporozoites stored in liquid nitrogen (LN(2))
      vapor phase (LNVP) below -140 degrees C and would be distributed through a LNVP
      cold chain. The purpose of this study was to model LNVP cold chain distribution
      for the cryopreserved PfSPZ Vaccine in Tanzania, estimate the costs and compare
      these costs to those that would be incurred in distributing a 'conventional'
      malaria vaccine through the EPI. Capital and recurrent costs for storage,
      transportation, labor, energy usage and facilities were determined for the birth
      cohort in Tanzania over five years. Costs were calculated using WHO/UNESCO
      calculators. These were applied to a 2-8 degrees C distribution model with
      national, regional, district, and health facility levels, and for the
      cryopreserved vaccine using a 'modified hub-and-spoke' (MH-S) LNVP distribution
      system comprising a central national store, peripheral health facilities and an
      intermediate district-level transhipment stop. Estimated costs per fully
      immunized child (FIC) were $ 6.11 for the LNVP-distributed cryopreserved vaccine
      where the LN(2) is generated, and $ 6.04 with purchased LN(2) (assuming US $
      1.00/L). The FIC costs for distributing a conventional vaccine using the four
      level 2-8 degrees C cold chain were $ 6.10, and with a tariff distribution system
      as occurs in Tanzania the FIC cost was $ 5.53. The models, therefore, predicted
      little difference in 5-year distribution costs between the PfSPZ Vaccine
      distributed through a MH-S LNVP cold chain and a conventional vaccine distributed
      through the more traditional EPI system. A LNVP cold chain provides additional
      benefits through the use of durable dry shippers because no refrigerators,
      freezers or refrigerated trucks are required. Thus strain at the cold chain
      periphery, vaccine wastage from cold chain failures and the environmental impact
      of distribution would all be reduced.

PMID- 23146677
TI  - Anti-melanoma vaccinal capacity of CD11c-positive and -negative cell populations
      present in GM-CSF cultures derived from murine bone marrow precursors.
AB  - We have initially shown that DC/ApoNec vaccine can induce protection against the
      poorly immunogenic B16F1 melanoma in mice. The population of DC obtained for
      vaccination after 7days culture with murine GM-CSF is heterogeneous and presents
      about 60% of CD11c+ DC. Therefore, our purpose was to identify the phenotype of
      the cells obtained after differentiation and its immunogenicity once injected. DC
      were separated with anti-CD11c microbeads and the two populations identified in
      terms of CD11c positivity (DC+ and DC-) were also studied. Approximately 26.6% of
      the cells in DC+ fraction co-expressed CD11c+ and F4/80 markers and 75.4% were
      double positive for CD11c and CD11b markers. DC+ fraction also expressed Ly6G. DC
      fraction was richer in CD11c-/F4/80+ macrophages (44.7%), some of which co
      expressed Ly6G (41.8%), and F4/80-/Ly6-G+ neutrophils (34.6%). Both DC+ and DC-
      fractions displayed similar capacity to phagocyte and endocyte antigens and even
      expressed levels of MHC Class II and CD80, CD83 and CD86 costimulatory molecules
      similar to those in the DC fraction. However, only DC/ApoNec vaccine was capable
      to induce protection in mice (p<0.01). After 24h co-culture, no detectable level
      of IL-12 was recorded in DC/ApoNec vaccine, either in supernatant or
      intracellularly. Therefore, the protection obtained with DC/ApoNec vaccine seemed
      to be independent of the vaccine's ability to secrete this inflammatory cytokine
      at the time of injection. In conclusion, we demonstrated that all cell types
      derived from the culture of mouse bone marrow with GM-CSF are necessary to induce
      antitumor protection in vivo.

PMID- 23146678
TI  - Correlates of seasonal flu vaccination among U.S. home health aides.
AB  - INTRODUCTION: Home health aides (HAs) receive limited training and reach many
      older patient populations highly susceptible to influenza virus. We sought to
      examine socio-demographic correlates of seasonal flu vaccination receipt among
      HAs. METHODS: We analyzed data from the 2007 U.S. National Home Health Aide
      Survey, a nationally representative sample of HAs reporting on occupational
      status, job and demographic characteristics and receipt of seasonal flu vaccine
      (n=3377). RESULTS: Seasonal flu vaccine receipt was low among all types of HAs
      (43.9%). After adjustment for socio-demographic indicators (i.e. age, gender,
      race and health insurance), home health, home care, hospice and personal care
      attendants were significantly less likely to report receiving seasonal flu
      vaccine as compared to licensed nursing assistants (adjusted odds ratio,
      AOR=0.42, 95% CI [0.20-0.85]; 0.41, [0.17-0.99]; 0.50, [0.26-0.97], and 0.53,
      [0.26-0.99], respectively). CONCLUSION: Targeted effective vaccination campaigns
      are needed to improve vaccination rates among home health aides.

PMID- 23146679
TI  - DNA vaccine encoding the major virulence factors of Shiga toxin type 2e (Stx2e)
      expressing Escherichia coli induces protection in mice.
AB  - Piglet edema disease is found worldwide and has historically been treated with
      antibiotics. However, no commercial vaccines are available for its prevention. In
      this study, the two major virulence factors of Shiga-toxigenic Escherichia coli
      (Stx2eB and FedF) were cloned to a pcDNA6.0 plasmid to develop a novel DNA
      vaccine against piglet edema disease. In animal trial in mouse model, the
      antibody titer, mortality, serum cytokine levels (interleukin-1 beta, interleukin
      6, tumor necrosis factor alpha and C-reactive protein), serum malondialdehyde
      level and serum total superoxide dismutase activity were measured to validate the
      effectiveness of the DNA vaccine. The results show that Stx2eB and FedF at least
      partially protect against edema disease and FedF is more effective than Stx2eB.
      Co-immunization with both Stx2eB and FedF is most effective for protecting mice
      from a subsequent challenge with E. coli O139 (which is known to cause edema
      disease in pigs).

PMID- 23146680
TI  - What do you eat? Dietary omega 3 can help to slow the aging process.

PMID- 23146681
TI  - Neural correlates of altered response inhibition and dysfunctional connectivity
      at rest in obsessive-compulsive disorder.
AB  - OBJECTIVE: Functional imaging studies of obsessive-compulsive disorder (OCD) have
      reported altered fronto-striatal activity during executive tasks. Additionally,
      altered connectivity of these regions during resting state was found. However,
      the relationship between brain activity during tasks and resting state remains
      poorly understood. The present study investigated neural correlates associated
      with abnormal response inhibition in OCD and to examine how resting state
      functional connectivity relates to task-related activity. METHOD: Eighteen
      unmedicated adult OCD patients and 18 age- and sex-matched control subjects
      underwent functional magnetic resonance imaging scans during both resting state
      and a response inhibition task. Brain activation during response inhibition was
      compared between groups. Fronto-striatal regions showing altered task-related
      activity were used as seeds for connectivity analyses during resting state.
      RESULTS: During the response inhibition task, OCD patients had lower activation
      in areas including the cingulate cortex and basal ganglia regions. Compared with
      control subjects, patients with OCD showed increased functional connectivity of
      the caudate nucleus with the middle cingulate cortex and precentral gyrus during
      rest, suggesting hyperactive striatal-cortical connections. CONCLUSION: This
      study found altered function in fronto-striatal regions during response
      inhibition and its relation to resting state functional connectivity in OCD. Our
      results suggest that dysfunctional striatal-cortical connections even during rest
      may result in the failure of response inhibition and error monitoring observed in
      OCD patients.

PMID- 23146682
TI  - Retinal vessel tortuosity measures and their applications.
AB  - Structural retinal vascular characteristics, such as vessel calibers, tortuosity
      and bifurcation angles are increasingly quantified in an objective manner, slowly
      replacing subjective qualitative disease classification schemes. This paper
      provides an overview of the current methodologies and calculations used to
      compute retinal vessel tortuosity. We set out the different parameter
      calculations and provide an insight into the clinical applications, while
      critically reviewing its pitfalls and shortcomings.

PMID- 23146683
TI  - MicroRNA in aqueous humor from patients with cataract.
AB  - MicroRNAs (miRNAs) are small non-coding RNA molecules with regulatory function
      and marked tissue specificity that can modulate multiple gene targets. They have
      been detected in body fluids and are associated with various physiologic and
      pathologic processes. We analyzed aqueous humor (AH) from human subjects
      undergoing cataract surgery to establish the presence and relative quantities of
      known miRNAs. AH was collected from patients without known ocular diseases other
      than cataract and a normal systemic history. Quantitative real-time PCR in an
      array platform was used to detect known miRNAs present in the AH. Among the 264
      miRNAs tested, 110 were present in the AH. The top 5 abundant miRNAs identified
      were miR-202, miR-193b, miR-135a, miR-365, and miR-376a. The presence of miRNAs
      in AH suggests that they may have functional roles in regulating target genes in
      tissues lining the anterior chamber. Further analysis of the AH miRNA population
      may identify potential gene targets and provide insights regarding their roles in
      AH regulation, glaucoma and anterior segment disease processes.

PMID- 23146684
TI  - Infectivity of Cryptosporidium andersoni Kawatabi type relative to the small
      number of oocysts in immunodeficient and immunocompetent neonatal and adult mice.
AB  - Cryptosporidium andersoni is a protozoan parasite found in many countries that
      invades the stomachs of primarily adult cattle. Unlike the isolates of C.
      andersoni in cattle from other countries, C. andersoni isolates from Japanese
      cattle can infect mice and were identified as a novel type and later defined as
      C. andersoni Kawatabi type. The biological characteristics of C. andersoni
      Kawatabi type have not yet been well documented. In the present study, we assess
      the infectivity of this type isolate in mice with different immune competence
      status and age. We found that inoculation of more than 1*10(4) oocysts is needed
      to establish infection in mature mice irrespective of immune status. All of the
      infected immunocompetent mice recovered after a patent period of approximately
      20days. In immunodeficient mice, the pre-patent period was prolonged compared
      with that of 1*10(6) oocysts, but the pattern and the maximum shedding measured
      by the number of oocysts per day were almost identical. In neonatal
      immunocompetent and immunodeficient mice, inoculation with 1*10(4) to 10(5)
      oocysts was also needed to establish infection. Our results indicate that there
      is a threshold of oocysts needed to establish patent infection in the acidic
      conditions of the stomach.

PMID- 23146685
TI  - Enhanced expression of LAG-3 on lymphocyte subpopulations from persistently
      lymphocytotic cattle infected with bovine leukemia virus.
AB  - An immunoinhibitory receptor, lymphocyte activation gene-3 (LAG-3), which is
      mainly expressed in T-cells, is involved in the immune evasion of several
      pathogens causing chronic infections and tumors. However, unlike human or mouse
      LAG-3, no functional analysis of LAG-3 has been reported in domestic animals.
      Thus, in this study, bovine LAG-3 expression was analyzed in bovine leukemia
      virus (BLV)-infected cattle. In persistent lymphocytotic (PL) cattle, the numbers
      of LAG-3(+)CD4(+) cells and LAG-3(+)CD8(+) cells were conserved whilst the number
      of MHC class II(+) cells was remarkably higher than in the control animals. In
      contrast, the mean fluorescence intensity (MFI) for LAG-3 on PBMCs from PL cattle
      was significantly increased compared to control and asymptomatic (AL) cattle.
      Specifically, the LAG-3 expression level was significantly increased in both
      CD4(+) and CD8(+) T cells from PL cattle. LAG-3 expression correlated positively
      with increased numbers of lymphocytes and MHC class II(+) cells in infected
      animals. Preliminary results from PD-L1 and LAG-3 blockade assay revealed that
      IFN-gamma and IL-2 expressions were significantly up-regulated by addition of
      anti- PD-L1 and LAG-3 antibodies in PBMCs from PL cattle. These findings suggest
      that LAG-3 might be involved in the inhibition of T-cell function through its
      binding and signaling on MHC class II molecule during BLV infection.

PMID- 23146686
TI  - Prognostic value of responsiveness of neoadjuvant chemotherapy before surgery for
      patients with stage IB(2)/IIA(2) cervical cancer.
AB  - OBJECTIVE: To evaluate the factors that might affect the putative survival
      benefit from pre-operative neoadjuvant chemotherapy (NAC) in patients with early
      stage bulky cervical cancer. METHODS: A retrospective review for 304 patients
      with stage IB(2)/IIA(2) cervical cancer was performed. Two groups were made
      according to pre-operative NAC or not: NAC group (n=154) and primary surgery
      group (PST, n=150). Recurrence risks and survival were analyzed. RESULTS: The
      total response rate was 72.1%. For those NAC-responders, NAC decreased the ratio
      of lymphovascular space invasion (0 vs. 4.7%, p=0.022; 0 vs. 3.3%, p=0.052), deep
      stromal invasion (19.8% vs. 53.5%, p=0.000; 19.8% vs. 29.3%, p=0.08), lymph node
      metastasis (8.1% vs. 25.6%, p=0.004; 8.1% vs. 17.3%, p=0.031), and the need of
      adjuvant radiotherapy (5.5% vs. 30.2%, p=0.000; 5.4% vs. 15.3%, p=0.012), whereas
      improve 5-year PFS rate (94% vs. 86%, p=0.041; 94% vs. 80%, p=0.089) and 5-year
      OS rate (96% vs. 86%, p=0.015; 96% vs. 82%, p=0.05), as compared with non
      responders and PST. Multivariate analysis suggested that the response to NAC is
      an independent prognostic factor of PFS (HR 0.221, 95% CI 0.048-1.022, p=0.053)
      and OS (HR 0.126, 95% CI 0.016-1.000, p=0.05); as compared, stage IIA disease
      demonstrates negative impact upon PFS (HR 4.778, 95% CI 1.490-15.317, p=0.009)
      and OS (HR 4.142, 95% CI 1.258-13.639, p=0.019). CONCLUSION: Responsiveness of
      NAC before surgery might be an independent prognostic factor for the patients
      with early stage bulky cervical cancer.

PMID- 23146689
TI  - [Cardiac magnetic resonance and cardiovascular risk].

PMID- 23146688
TI  - The role of co-factors in the progression from human papillomavirus infection to
      cervical cancer.
AB  - OBJECTIVE: Co-factors for cervical cancer, including oral contraceptive (OC) use,
      smoking and multiparity have been identified; however, the stage at which they
      act in cervical carcinogenesis is not clear. We compared established risk factors
      among women with CIN2 and CIN3 to evaluate the heterogeneity of these factors in
      precancer and also assessed their role during cervical carcinogenesis. METHODS:
      The current analysis included 2783 women with various stages of cervical disease
      who were enrolled in the Study to Understand Cervical Cancer Early Endpoints and
      Determinants (SUCCEED) and the Biopsy Study. Associations of co-factors within
      cervical precancer and at different stages of cervical carcinogenesis were
      estimated using logistic regression. RESULTS: Long-term OC use (10+years vs.
      never: OR=2.42, 95% CI: [1.13-5.15]), multiparity (3+ births vs. nulliparous:
      OR=1.54 [1.04-2.28]), smoking (ever vs. never: OR=1.95 [1.48-2.58]), and no Pap
      test in the previous five years (2.05 [1.32-3.17]) were positively associated
      with CIN3 compared to CIN2. We observed that long-term OC use, parity and smoking
      were associated with an increased risk of CIN3 compared to <CIN2 (1.97 [1.12
      3.46]; 2.23 [1.59-3.11]; 2.60 [2.04-3.30], respectively), whereas associations
      were not significantly different (OC use, parity) or showed decreased risk
      (smoking) when comparing cancer to CIN3. CONCLUSIONS: Differences in established
      risk factors suggest that CIN3 is a more specific definition of precancer than
      CIN2. Hormonally-related factors and smoking play a role in the transition from
      human papillomavirus infection to precancer.

PMID- 23146687
TI  - Induction of mitotic cell death by overriding G2/M checkpoint in endometrial
      cancer cells with non-functional p53.
AB  - OBJECTIVE: Endometrial tumors with non-functional p53, such as serous uterine
      endometrial carcinomas, are aggressive malignancies with a poor outcome, yet they
      have an Achilles' heel: due to loss of p53 function, these tumors may be
      sensitive to treatments which abrogate the G2/M checkpoint. Our objective was to
      exploit this weakness to induce mitotic cell death using two strategies: (1) EGFR
      inhibitor gefitinib combined with paclitaxel to arrest cells at mitosis, or (2)
      BI2536, an inhibitor of polo-like kinase 1 (PLK1), to block PLK1 activity.
      METHODS: We examined the impact of combining gefitinib and paclitaxel or PLK1
      inhibitor on expression of G2/M checkpoint controllers, cell viability, and cell
      cycle progression in endometrial cancer cells with mutant p53. RESULTS: In cells
      lacking normal p53 activity, each treatment activated CDC25C and inactivated
      Wee1, which in turn activated cdc2 and sent cells rapidly through the G2/M
      checkpoint and into mitosis. Live cell imaging demonstrated irreversible mitotic
      arrest and eventual cell death. Combinatorial therapy with paclitaxel and
      gefitinib was highly synergistic and resulted in a 10-fold reduction in the IC50
      for paclitaxel, from 14nM as a single agent to 1.3nM in the presence of
      gefitinib. However, BI2536 alone at low concentrations (5nM) was the most
      effective treatment and resulted in massive mitotic cell death. In a xenograft
      mouse model with p53-deficient cells, low dose BI2536 significantly inhibited
      tumor growth. CONCLUSIONS: These findings reveal induction of mitotic cell death
      as a therapeutic strategy for endometrial tumors lacking functional p53.

PMID- 23146690
TI  - Synergistic anti-cancer effects of resveratrol and chemotherapeutic agent
      clofarabine against human malignant mesothelioma MSTO-211H cells.
AB  - Dietary phytochemicals as adjuvants have been suggested to play important roles
      in enhancing chemotherapeutic potential owing to multitargeted chemopreventive
      properties and lack of substantial toxicity. Here, we investigated the efficacy
      of the combined treatment of various phytochemicals with the anticancer drug
      clofarabine in malignant mesothelioma MSTO-211H cells and normal mesothelial MeT
      5A cells. The combined treatment of resveratrol and clofarabine produced a
      synergistic antiproliferative effect in MSTO-211H cells, but not in MeT-5A cells.
      In MSTO-211H cells, the nuclear accumulation of Sp1 and the levels of p-Akt, Sp1,
      c-Met, cyclin D1, and p21 were effectively decreased by the combined treatment of
      them. In combination with clofarabine, the ability of resveratrol to reduce the
      contents of Sp1 and its target gene products was also evident in a time- and dose
      dependent experiment. The inhibition of phosphoinositide 3-kinase using Ly294002
      augmented a decrease in the p21 level induced by their combination, but it showed
      no significant effects on expression of Sp1 and cyclin D1. Taken together, the
      data provide evidence that the synergistic antiproliferative effect of
      resveratrol and clofarabine is linked to the inhibition of Akt and Sp1
      activities, and suggest that this combination may have therapeutic value in
      treatment of malignant mesothelioma.

PMID- 23146691
TI  - Emodin-6-O-beta-D-glucoside inhibits HMGB1-induced inflammatory responses in
      vitro and in vivo.
AB  - High mobility group box 1 (HMGB1) protein acts as a potent proinflammatory
      cytokine and is involved in the pathogenesis of several vascular diseases, such
      as, systemic vasculitis and sepsis. Emodin-6-O-beta-D-glucoside (EG) is a new
      active compound from Reynoutria japonica, and its biologic activities have not
      been previously investigated. In this study, we first investigated the
      antiinflammatory activities of EG on HMGB1-mediated proinflammatory responses in
      human umbilical vein endothelial cells (HUVECs) and in a murine cecal ligation
      and puncture (CLP)-model of sepsis in mice. EG was found to suppress the release
      of HMGB1, the production of tumor necrosis factor (TNF)-alpha, and the activation
      of nuclear factor-kappaB (NF-kappaB) by HMGB1 in HUVECs, and to inhibit HMGB1
      mediated hyperpermeability and leukocyte migration in mice. In the CLP model,
      HMGB1 was highly released, but this release was prevented by EG. Furthermore, EG
      also increased the survival times of CLP administered mice. Collectively, this
      study shows EG can protect barrier integrity and inhibit HMGB1-mediated
      inflammatory responses, which suggests a potential use as a therapy for sepsis or
      septic shock.

PMID- 23146692
TI  - Purification and determination of two novel antioxidant peptides from flounder
      fish (Paralichthys olivaceus) using digestive proteases.
AB  - We investigated the effects of bioactive-peptides from hydrolysates of flounder
      fish muscle (FFM) on antioxidant activity. The hydrolysates were prepared by
      enzymatic reactions of FFM using eight commercial proteases such as papain,
      pepsin, trypsin, neutrase, alcalase, kojizyme, protamex, and alpha-chymotrypsin.
      The alpha-chymotrypsin hydrolysate showed the strongest antioxidant activity
      among the eight enzymatic hydrolysates. Further separation of the alpha
      chymotrypsin hydrolysate was performed by ultrafiltration, gel filtration, and
      reverse-phase high performance liquid chromatography. Consequently, two novel
      peptides with high antioxidant activity were purified, and their amino acid
      sequences were determined (Val-Cys-Ser-Val [VCSV] and Cys-Ala-Ala-Pro [CAAP],
      respectively). The two peptides showed good scavenging activity against the 1,1
      diphenyl-2-picrylhydrazyl (DPPH) free radical (IC(50) values, 111.32 and 26.89
      MUM, respectively) and high cytoprotective activities against 2,2-azobis-(2
      amidino-propane) dihydrochloride (AAPH) without cytotoxicity and scavenged total
      reactive oxygen species in Vero cells. In particular, apoptotic bodies produced
      by AAPH dose-dependently decreased following treatment with the CAAP peptide.
      These results revealed firstly the two peptides with strong antioxidative effects
      from FFM.

PMID- 23146693
TI  - The relation between dietary habits and urinary levels of 3-phenoxybenzoic acid,
      a pyrethroid metabolite.
AB  - Concerns about pesticide exposure through food consumption have increased during
      the past several years. Pyrethroids are applied as insecticides throughout the
      world. Human metabolism of pyrethroids results in urinary metabolites that are
      suitable for biological monitoring. The objective of our study was to investigate
      the relation between food consumption and urinary levels of 3-phenoxybenzoic acid
      (3-PBA), a general metabolite of pyrethroids, in a non-occupational exposed adult
      population from the IDI-IRCCS, Rome, Italy. Information on socio-demographic
      characteristics, smoking, diet and self-reported household pesticide exposure was
      collected. Urinary 3-PBA level of each subject was measured and adjusted by
      urinary creatinine. We found that people consuming both raw and cooked vegetables
      five times weekly or more had higher mean levels of 3-PBA in urine (1.03 MUg/g
      creatinine versus 0.52 MUg/g creatinine; p=0.009 and 0.99 MUg/g creatinine versus
      0.58 MUg/g creatinine; p=0.01, respectively) than subjects consuming less than
      five times weekly. In a multivariate model, after adjusting for age, sex, BMI,
      smoking and household insecticide exposure, high intake of raw vegetables (OR:
      5.31; 95%CI: 1.32-21.3) and high intake of cooked vegetables, in particular
      cruciferous (OR: 4.67; 95%CI: 1.07-20.5) and leafy vegetables (OR: 6.88; 95%CI:
      1.50-31.7), were associated with high urine 3-PBA levels (>=0.70 MUg/g
      creatinine). The results of this study suggest that part of the variation in
      pyrethrois intake is explained by vegetable intake.

PMID- 23146694
TI  - Bisphenol A inhibits proliferation and induces apoptosis in micromass cultures of
      rat embryonic midbrain cells through the JNK, CREB and p53 signaling pathways.
AB  - Bisphenol A (BPA) has been widely used in the manufacture of polycarbonate
      plastic, water bottles and food containers. Previous studies have established
      that BPA could cause developmental toxicity by inhibiting the proliferation and
      differentiation of rat embryonic midbrain (MB) cells in vitro. However, the
      underlying mechanisms have not been well studied yet. In the current study, we
      examined the proliferation and differentiation of MB cells treated with 10(-12)
      10(-4)M BPA and found that only 10(-4)M BPA inhibited proliferation and
      differentiation. Then, we investigated the cell cycle progression and apoptosis
      of MB cells; 10(-4)M BPA caused an explicit S phase and G2/M phase arrest in the
      cell cycle and increased the percentage of apoptotic cells. Moreover, the
      phosphorylation of mitogen-activated protein kinase (MAPK) and cyclic-AMP
      response binding protein (CREB) and the expression of some apoptotic regulatory
      genes were investigated. BPA (10(-4)M) reduced the phosphorylation of C-Jun N
      terminal kinase (JNK) and CREB, and increased the mRNA expression level of Bax
      and p53. Our findings demonstrated that BPA could cause developmental toxicity
      through anti-proliferation and pro-apoptosis in MB cells. Multiple signaling
      pathways, such as the JNK, CREB and p53-mitochondrial apoptosis pathways,
      participate in these effects.

PMID- 23146695
TI  - Puerarin mediates hepatoprotection against CCl4-induced hepatic fibrosis rats
      through attenuation of inflammation response and amelioration of metabolic
      function.
AB  - This study was designed to evaluate the potential effects of puerarin (PR), an
      effective isoflavonoid compound purified from Pueraria lobata, in treating
      hepatic fibrosis (HF) rats induced by carbon tetrachloride (CCl(4), 2 mL kg(-1)
      d(-1)). Compared to model control, PR treatment effectively lowered the serum
      levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST),
      albumin (Alb), total protein (TP) in HF rats. Masson stained analysis showed that
      the condition of HF rats was mitigated. Meanwhile, the tumor necrosis factor
      alpha (TNF-alpha), nuclear factor-kappa B (NF-kappaB) expressions were
      significantly down-regulated at protein level by PR intervention. Additionally,
      the activity of superoxide dismutase (SOD) was elevated, while the content of
      malondialdehyde (MDA) was lessened in liver tissue. As revealed by
      immunohistochemistry assay, PR therapy resulted in reduced production of
      transforming growth factor-betal (TGF-betal). Moreover, it also was attributed to
      decreased mRNA level of inducible nitric oxide synthase (iNOS) using RT-PCR
      analysis. These findings demonstrate that puerarin successfully reverses
      hepatotoxicity in CCl(4)-induced HF rats via the underlying mechanisms of
      regulating serum enzymes and attenuating TNF-alpha/NF-kappaB pathway for anti
      inflammation response, as well as improving metabolic function in liver tissue.

PMID- 23146696
TI  - WITHDRAWN: Effects of oral administration of Bacillus thuringiensis as spore
      crystal strains Cry1Aa, Cry1Ab, Cry1Ac or Cry2Aa on hematologic and genotoxic
      endpoints of Swiss albino mice.
AB  - This article has been withdrawn at the request of the author(s) and/or editor.
      The Publisher apologizes for any inconvenience this may cause. The full Elsevier
      Policy on Article Withdrawal can be found at
      http://www.elsevier.com/locate/withdrawalpolicy.

PMID- 23146697
TI  - Answers to critics: Why there is a long term toxicity due to a Roundup-tolerant
      genetically modified maize and to a Roundup herbicide.
AB  - Our recent work (Seralini et al., 2012) remains to date the most detailed study
      involving the life-long consumption of an agricultural genetically modified
      organism (GMO). This is true especially for NK603 maize for which only a 90-day
      test for commercial release was previously conducted using the same rat strain
      (Hammond et al., 2004). It is also the first long term detailed research on
      mammals exposed to a highly diluted pesticide in its total formulation with
      adjuvants. This may explain why 75% of our first criticisms arising within a
      week, among publishing authors, come from plant biologists, some developing
      patents on GMOs, even if it was a toxicological paper on mammals, and from
      Monsanto Company who owns both the NK603 GM maize and Roundup herbicide (R). Our
      study has limits like any one, and here we carefully answer to all criticisms
      from agencies, consultants and scientists, that were sent to the Editor or to
      ourselves. At this level, a full debate is biased if the toxicity tests on
      mammals of NK603 and R obtained by Monsanto Company remain confidential and thus
      unavailable in an electronic format for the whole scientific community to conduct
      independent scrutiny of the raw data. In our article, the conclusions of long
      term NK603 and Roundup toxicities came from the statistically highly discriminant
      findings at the biochemical level in treated groups in comparison to controls,
      because these findings do correspond in an blinded analysis to the pathologies
      observed in organs, that were in turn linked to the deaths by
      anatomopathologists. GM NK603 and R cannot be regarded as safe to date.

PMID- 23146698
TI  - Hepatoprotective effects of Gentiana asclepiadea L. extracts against carbon
      tetrachloride induced liver injury in rats.
AB  - This study is an attempt to evaluate the hepatoprotective activity of Gentiana
      asclepiadea L. against carbon tetrachloride-induced liver injury in rats.
      Methanol extracts of aerial parts (GAA) and roots (GAR) of G. asclepiadea at
      doses of 100, 200, and 400mg/ kg b.w. were orally administered to Wistar rats
      once daily for 7 days before they were treated with CCl(4). The hepatoprotective
      activity of the extracts in this study was compared with the reference drug
      silymarin. In CCl(4) treated animals, GAA and GAR significantly decreased levels
      of serum transaminases, alkaline phosphatase and total bilirubin, and increased
      the level of total protein. Treatment with the extracts resulted in a significant
      increase in the levels of catalase, superoxide dismutase and reduced glutathione,
      accompanied with a marked reduction in the levels of malondialdehyde, as compared
      to CCl(4) treated group. The histopathological studies confirmed protective
      effects of extracts against CCl(4)-induced liver injuries. No genotoxicity was
      observed in liver cells after GAA treatment, while GAR showed only slight
      genotoxic effects by comet assay. Phytochemical analysis revealed the presence of
      sweroside, swertiamarin and gentiopicrin in high concentrations in both extracts.
      It could be concluded that the use of G. asclepiadea extracts in the treatment of
      chemical-induced hepatotoxicity.

PMID- 23146699
TI  - [Law on sanitary measures against smoking. Two years of implementation].

PMID- 23146700
TI  - [How we treat subclinical hypothyroidism in our daily clinical practice].
AB  - OBJECTIVE: To study the therapeutic approach to subclinical hypothyroidism (HTS),
      the frequency of introducing replacement therapy, reasons for starting, doses,
      and duration, in the population over 14 years-old in a Primary Care Centre.
      MATERIAL AND METHODS: Longitudinal, retrospective observational study of 1156
      patients with a hypothyroidism/myxedema episode (T86 in the International
      Classification of Primary Care (ICPC)) entered in the OMI program were studied.
      Excluded: 10 duplicates, 180 no inclusion criteria or inability to collect data,
      25 diagnosed in another laboratory, 359 with clinical hypothyroidism (HTC).
      MEASUREMENTS: Sex, age, TSH value to diagnosis and initiate treatment, or latest
      TSH recorded in the clinical history (HC) if not treated, TSH diagnostic
      confirmation, antiTPO antibodies (ATAs), presence of fatigue, goitre,
      neuropsychiatric symptoms, raised cholesterol, if HTS secondary, progression to
      HTC, diagnostic-start treatment interval, initial and final dose, duration,
      reasons for discontinuation. RESULTS: 582 patients: 508 women. Mean age: 43.03
      (sd 15.97). HTS treated: 330 (56.7%); TSH at diagnosis < 10: 81.6%; Mean TSH
      treated: 11.22 (sd 10.49); Made ATAs performed: 315 (54%),+166 (52.7%); Fatigue
      not recorded in HC: 64%; Goitre: 65%. 67% untreated: returned to normal
      spontaneously. Starting dose: 86% <= 50MUg. Final <= 50: 43%. Treatment duration:
      1-5 years 41%; > 5 years 40%. Immediate treatment after diagnosis 38%. Remain
      treated 93%. Variables that increase the likelihood of onset of treatment
      (Logistic Regression): TSH value (OR 32.5, CI 12.8- 82.6), ATAs+(OR 4.7, CI 2.8
      7.7); Fatigue (OR 2.5, CI 1.5-4), Goitre (OR 3, CI 1.3-6.6). CONCLUSIONS: The
      decision to treat is generally adequate, but often becomes a chronic analytical
      disorder, because of unduly prolonged treatment without attempts to withdraw it.
      Clinical history and physical examination tend to be ignored.

PMID- 23146701
TI  - [Nodal affectation in laryngeal cancer and therapeutic procedures].
AB  - AIMS: Try to establish a relationship between the presence or absence of
      lymphadenopathy in tumors of the larynx and the location of the tumor and discuss
      the treatment required in each case. METHODS: Data collection sheets were
      designed for the 224 laryngeal cancer cases diagnosed in the province of
      Guadalajara between 1975 and 1998, among those data we included the presence or
      absence of lymph nodes at the time of diagnosis, as well as its location and
      treatment applied in each patient. RESULTS: About in a half the cases studied had
      lymphadenopathy, being about in a half of the cases unilateral and about in a
      half of the cases bilaterals. The lymph nodes appeared more frequently in the
      supraglottic and hypopharyngeal tumors and less frequently in the glottic tumors.
      More extensive surgical interventions corresponded to supraglottic tumors and
      those affecting multiple levels of the larynx. Lymph node dissection was required
      in the 87% of supraglottic tumors and in 38.6% of the glottic tumors.
      CONCLUSIONS: The bigger size of the tumor correlated with more cases with
      lymphadenopathies and a more extensive treatment had to be applied.

PMID- 23146702
TI  - [Reported prevalence of family history of colorectal cancer in the city of Gijon
      (Spain)].
AB  - INTRODUCTION: The objective of this study was to determine the prevalence of
      family history of colorectal cancer (CRC) in a population between 40 and 75 years
      old, as well as acceptability and early diagnosis tests made. MATERIAL AND
      METHODS: Cross-sectional study. LOCATION: El Coto and El Llano (Gijon) primary
      care health centres. A total of 800 individuals aged between 40 and 75 years
      participated, selected by simple random sampling. Key measurements: questionnaire
      conducted by telephone with previous notice by newsletter. The variables studied
      were: family history (FH) of CRC, age at diagnosis, performance of faecal occult
      blood test (FOBT)/colonoscopy, reason for doing it or refusing it, and
      sociodemographic data. RESULTS: A total of 664 questionnaires were valid. The
      prevalence of FH was 15.8% (confidence interval 12.9 to 18.6), with 8.8% with at
      least one first degree relative. An FOBT screening had been performed on 7.1%,
      and 17.9% had undergone colonoscopies, mostly on clinical grounds. Acceptability
      was 90.7% for FOBT and 65.2% for colonoscopy. Main reason for the refusal of an
      FOBT was the belief that early diagnosis would not alter prognosis. Main reason
      for rejection of colonoscopy was discomfort or fear of the test. CONCLUSIONS:
      There was a low rate of testing for FH, and a high acceptability for FOBT and a
      low acceptability for colonoscopy. Aspects affecting the general population
      (causes for rejection, need for clear information), as well as a correct
      coordination between Primary Care, specialized care, and public health, need to
      be reviewed.

PMID- 23146703
TI  - [Advantages and drawbacks of current pharmacological treatments for smoking
      cessation].
AB  - There are currently three families of drugs that are commonly used in the clinic
      to help smokers to stop; nicotine replacement therapy, bupropion and varenicline.
      Summary knowledge of the specific efficacy and contraindications of each of them
      can be useful before prescribing them to our patients.

PMID- 23146704
TI  - [Consensus on integrated care of acute exacerbations of chronic obstructive
      pulmonary disease (ATINA-EPOC). Part IV].

PMID- 23146705
TI  - [Elephantiasis nostras verrucosa in a patient with major depressive disorder].
AB  - Elephantiasis nostras verrucosa is a rare condition characterised by papules,
      verrucous lesions, fibrosis and deformity of the affected area. It is caused by
      chronic lymphedema that could be congenital or produced by a non-associated
      infection (such as tuberculosis, mycotic infection, syphilis), surgery,
      radiotherapy, trauma, neoplastic obstruction, obesity, portal hypertension, or
      congestive heart failure. There is no standard treatment for this rare skin
      disorder. Depending on the cause and the severity, the treatment can be medical
      or surgical. We report the case of a man seen in our hospital with a major
      depression and elephantiasis nostras verrucosa skin lesions on both legs, who was
      successfully treated with surgical debridement and conservative measures.

PMID- 23146706
TI  - [A woman with painful subcutaneous nodules and dyspnea].
AB  - Sarcoidosis is a multisystem chronic disease characterised by the accumulation of
      inflammatory cells into the affected tissue, secondary to excessive cellular
      immune response. It can occur in any organ, although the most common is the lung.
      The skin lesions of sarcoidosis are only present in 25-30% of patients, and have
      a highly variable clinical expression. We report the case of a 57 year-old woman
      who consulted a dermatologist for painful subcutaneous nodules, and describe her
      history of fatigue and severe dyspnea. Due to the presence of dyspnea a chest x
      ray was requested, which showed changes in the parenchyma and hilum. A skin and
      transbronchial biopsy was subsequently performed, which confirmed the diagnosis
      of sarcoidosis. The skin and lung lesions subsided after prolonged treatment with
      oral adrenal cortex hormones.

PMID- 23146707
TI  - [Retroperitoneal schwannoma].
AB  - Schwannomas, also called neurilemmomas, are a rare type of tumour in the body and
      even more rare in the retroperitoneal cavity. They arise from Schwann cells of
      the peripheral nerves. Retroperitoneal Schwannomas are rare and they account for
      0.7 to 2.7% of all Schwannomas. They are slow growing tumours, and their location
      in the retroperitoneum is associated with poor clinical symptoms, and is often an
      incidental radiographic finding. Although it is a histologically benign tumour,
      we must not under-estimate the damage caused by compression of adjacent
      structures, as well as the rare but possible malignant transformation. We present
      this case as a casual finding after a systematic examination of the patient
      performed for assessment of his hypertension, with an abdominal mass being the
      principal finding.

PMID- 23146708
TI  - [An uncommon case of proximal Crohn's disease].
AB  - Crohn's disease (CD) is a chronic, inflammatory disorder that can involve any
      part of the gastrointestinal tract, from the mouth to the anus. Although CD
      mainly affects the terminal ileum and colon, the involvement of the upper
      gastrointestinal tract rarely occurs. Diagnosis is based on clinical, endoscopic
      and histological features. Treatment for CD of the upper gastrointestinal tract
      is similar to distal CD therapy. Corticosteroids added to proton pump inhibitors
      are usually used. The case of a 42-year-old female patient with CD located in the
      oesophagus, stomach and duodenum is presented. Among the complementary tests, an
      endoscopic evaluation of the upper gastrointestinal tract with biopsies was
      essential to support CD diagnosis.

PMID- 23146709
TI  - [Pellegrini-Stieda syndrome as a cause of knee pain].
AB  - Calcification in the soft tissue next to the medial femoral condyle after a
      history of trauma around the knee is a recognized radiographic finding-PS
      (Pellegrini-Stieda) sign. When this is associated with pain and a restricted
      range of motion it is known as the PS syndrome. We describe two cases of PS
      syndrome, treated conservatively with rest and physiotherapy, as well as the
      radiographic and ultrasound findings, and the many theories proposed in attempts
      to explain the pathogenesis of PS disease.

PMID- 23146710
TI  - [Tuberculosis: is it still a public health problem?].

PMID- 23146711
TI  - [Antibiotics, but with discretion].

PMID- 23146713
TI  - Stretch reflex spatial threshold measure discriminates between spasticity and
      rigidity.
AB  - OBJECTIVE: Muscle spasticity following stroke has been shown to result from
      limitations in the range of regulation of the tonic reflex spatial threshold
      (ST), i.e., the joint angle at which the stretch reflex begins to act due to
      descending and segmental influences on motoneurons. The purpose of this study was
      to determine whether spasticity due to stroke and rigidity due to parkinsonism
      can be discriminated based on the ST measure. METHODS: Elbow muscles were
      stretched at different velocities in healthy, stroke (spasticity) and
      parkinsonism (rigidity) subjects. The elbow angle at which muscle activation
      began for each stretch velocity (dynamic ST) and the velocity sensitivity of the
      ST were measured. Dynamic ST values extrapolated to zero velocity defined the
      tonic ST. RESULTS: Compared to healthy subjects, spasticity and rigidity were
      associated with a decrease in the range of central regulation of tonic STs. STs
      were hypersensitive in spastic muscles and either hypo- or inversely sensitive to
      stretch velocity in rigid muscles. CONCLUSIONS: ST characteristics discriminate
      between neurological deficits of muscle tone. SIGNIFICANCE: Results suggest that
      spasticity and rigidity result from deficits in descending facilitatory control
      combined with deficits in dynamic fusimotor or/and presynaptic control of Ia
      inputs to motoneurons.

PMID- 23146714
TI  - Cervical response among ascending ventrolateral funiculus pathways of the
      neonatal rat.
AB  - Propriospinal pathways, consisting of axons from interneurons that project to
      other spinal segments, have been implicated as likely candidates to mediate
      interlimb coordination in developing and adult mammals during quadrupedal
      locomotion. The superficial thoracic ventrolateral funiculus (VLF) contains both
      ascending and descending axons, and when stimulated can induce alternating
      rhythmic locomotor-like activity in the lumbar ventral roots of the isolated
      neonatal rat spinal cord. The goal of this work was to characterize the synaptic
      inputs onto cervical neurons from ascending axons in the VLF. Sprague-Dawley rats
      (P4-P7) were deeply anesthesized with halothane and their spinal cords were
      isolated, removed, and maintained in vitro. Intracellular recordings were made
      from 68 cervical (C5-C7) neurons having 71 latency classifications in response to
      thoracic VLF stimulation. Antidromic (n=35), monosynaptic (n=2), di-or tri
      synaptic (n=18) and long-latency polysynaptic (n=16) responses were recorded.
      Recordings from reduced preparations (mid-sagittal section at C5-C7) suggest that
      much of the delay in the long-latency polysynaptic responses require a
      bilaterally intact cervical spinal cord. Fifty-three percent (17/32) of the VLF
      responsive cervical interneurons tested also exhibited long latency excitatory
      responses to lumbar dorsal root stimulation suggesting that many of the cervical
      VLF responsive interneurons receive indirect input from lumbar primary afferents.
      We hypothesize that the VLF contains a population of ascending axons originating
      from lumbar propriospinal interneurons that can influence cervical inter- and
      motoneurons. These ascending VLF axons may participate in interlimb coordination
      by providing moment-by-moment feedback to the cervical enlargement of lumbar
      central pattern generator and/or hindlimb proprioceptive activity.

PMID- 23146715
TI  - Differential effects of intravesical resiniferatoxin on excitability of bladder
      spinal neurons upon colon-bladder cross-sensitization.
AB  - Cross-sensitization in the pelvis may contribute to etiology of functional pelvic
      pain disorders such as interstitial cystitis/bladder pain syndrome (IC/BPS).
      Increasing evidence suggests the involvement of transient receptor potential
      vanilloid 1 (TRPV1) receptors in the development of neurogenic inflammation in
      the pelvis and pelvic organ cross-sensitization. The objective of this study was
      to test the hypothesis that desensitization of TRPV1 receptors in the urinary
      bladder can minimize the effects of cross-sensitization induced by experimental
      colitis on excitability of bladder spinal neurons. Extracellular activity of
      bladder neurons was recorded in response to graded urinary bladder distension
      (UBD) in rats pretreated with intravesical resiniferatoxin (RTX, 10(-7)M).
      Colonic inflammation was induced by intracolonic instillation of 2,4,6
      trinitrobenzene sulfonic acid (TNBS). The duration of excitatory responses to
      noxious UBD during acute colonic inflammation (3 days post-TNBS) was
      significantly shortened in the group with RTX pretreatment (25.3+/-1.5s, n=49)
      when compared to the control group (35.1+/-4.2s, n=43, p<0.05). The duration of
      long-lasting excitatory responses, but not short-lasting responses of bladder
      spinal neurons during acute colitis was significantly reduced by RTX from 52.9+/
      6.6s (n=21, vehicle group) to 34.4+/-2.1s (RTX group, n=21, p<0.05). However,
      activation of TRPV1 receptors in the urinary bladder prior to acute colitis
      increased the number of bladder neurons receiving input from large somatic fields
      from 22.7% to 58.2% (p<0.01). The results of our study provide evidence that
      intravesical RTX reduces the effects of viscerovisceral cross-talk induced by
      colonic inflammation on bladder spinal neurons. However, RTX enhances the
      responses of bladder neurons to somatic stimulation, thereby limiting its
      therapeutic potential.

PMID- 23146716
TI  - Ligand-independent androgen receptor antagonism caused by the newly developed
      pesticide pyrifluquinazon (PFQ).
AB  - Androgen receptor (AR) is an essential component to activate AR dependent gene
      transcriptions. Despite wide acceptance of pharmacological controls on
      transcriptional pathway depending on competitive inhibitions of ligand binding,
      only a few examples, AR antagonism via ligand-independent mechanisms, have been
      recognized. Pyrifluquinazon(PFQ), a newly developed pesticide, induced
      representative AR antagonism against rats in in vivo and in vitro. Intriguingly,
      this AR antagonism was not based on inhibition of ligand binding. Instead, the
      evidence suggested that the AR antagonism was induced as a consequence of decline
      of cellular AR protein level. This study demonstrated that AR N-terminal region
      could be an essential element for a ligand-independent mechanism underling the AR
      antagonism by PFQ. Our findings should provide a novel insight into the
      regulation of AR-mediated transcription.

PMID- 23146717
TI  - A national survey examining the professional work life of today's nursing
      faculty.
AB  - OBJECTIVE: To examine factors that influence faculty member's work life in order
      to provide a supportive environment for recruiting and retaining nursing faculty.
      DESIGN: A cross-sectional non-experimental design incorporating correlation-based
      analyses gathered from a 45-item online survey. SETTING: The survey gauged
      several aspects of the nurse faculty work life, including teaching competence,
      productivity, and organizational support. PARTICIPANTS: US nurse faculty employed
      at either a CCNE or NLNAC accredited nursing program. METHODS: A stepwise linear
      regression analysis was conducted to ascertain which aspects of work life
      significantly predicted nurse faculty members' intent to stay or leave the
      faculty role. A one-way ANOVA examined whether faculty members' intent to stay or
      leave the faculty role varied as a function of generation. RESULTS: Data from 808
      useable surveys demonstrated that perceptions of administration's support for
      faculty improvement, perceptions of productivity, choice of pursuing a
      professional career in nursing, and the application of perceived teaching
      expertise significantly predicted faculty members' intent to stay or leave the
      faculty role. Moreover, generational membership influenced faculty members'
      intent to stay or leave the faculty role. CONCLUSIONS: Academic nurse
      administrators can positively affect the work life of their faculty and their
      intent to stay in the organization through support for the development of
      teaching and research roles with time and resources, recognition of faculty
      efforts, consideration of faculty needs from individual and generational
      perspectives, and targeted mentoring for career development.

PMID- 23146718
TI  - Evaluating the contribution of shape attributes to recognition using the minimal
      transient discrete cue protocol.
AB  - Subjects were tested for their ability to identify objects that were represented
      by an array of dots that marked the major contours, usually only the outer
      boundary. Each dot was briefly flashed to make its position known, and a major
      variable was the time interval that was required to flash all the dots for a
      given shape. Recognition declined as the total time for display of the dot
      inventory was increased. Each shape was shown to a given subject only once and it
      was either recognized -- named - or not. Although the recorded response was
      binary, a large number of subjects was tested, which made it possible to derive
      regression functions and thus specify an intercept and slope for each shape.
      Shapes differed substantially in their slopes, which is likely due to the amount
      of redundant information provided by neighboring dots. Indices of shape
      attributes were also derived, specifically Attneave's indices of complexity, mean
      curvature, inflection count, and symmetry. Three of the four shape attributes
      were significantly related to intercept and slope levels, but none made a
      substantial contribution. This suggests that these attributes are not essential
      properties that define shapes and allow for recognition.

PMID- 23146719
TI  - Analysis of the genetic variants of glucose-6-phosphate dehydrogenase in
      inhabitants of the 4th Nile cataract region in Sudan.
AB  - Malaria is one of the most common diseases in the African population. Genetic
      variance in glucose dehydrogenase 6-phosphate (G6PD) in humans determines the
      response to malaria exposure. In this study, we aimed to analyze the frequency of
      two single-nucleotide polymorphisms (G202A and A376G) present in two local tribes
      of Sudanese Arabs from the region of the 4th Nile cataract in Sudan, the Shagia
      and Manasir. The polymorphisms in G6PD were analyzed in 217 individuals (126
      representatives of the Shagia tribe and 91 of the Manasir tribe). Real-time PCR
      and RFLP-PCR were utilized to analyze significant differences in the prevalence
      of alleles and genotypes. The 202A G6P allele frequency was 0.7%, whereas the
      G202 variant was found in 93.3% of cases. The AA, GA, and GG genotype frequencies
      for the A376G G6PD codon among the Shagia were 88, 11.1, and 0.9%, respectively;
      this is similar to the distribution among Manasir tribe representatives (94.5,
      3.3, and 2.2%, respectively; OR 3.44 [0.85-16.17], p=0.6). Notably, in north
      eastern Sudan the G6PD B (202G/376A) compound genotype frequency was 90.3%,
      whereas the G6PD A variant (202G/376G) was found in 1.4% of that population.
      Identification of the G6PD A- variant (202A/376G) in the isolated Shagia tribe
      provides important information regarding the tribal ancestry. Taken together, the
      data presented in this study suggest that the Shagia tribe was still nomadic
      between 4000 and 12,000 years ago. Moreover, the lack of G6PD A- genotype among
      ethnically diverse Monasir tribesmen indicates a separation of the Shagia from
      the other tribes in the region of the 4th Nile cataract in Sudan.

PMID- 23146720
TI  - Characterization of dysphonic voices by means of a filterbank-based spectral
      analysis: sustained vowels and running speech.
AB  - OBJECTIVES: This article presents a comparative study of the spectral power
      distribution for normal and dysphonic voices, both for sustained vowels and
      running speech. The objective of this study was to find robust cues of dysphonia
      in spectral domain. For this purpose, recordings from two databases are
      processed, one of them including both sustained vowels and running speech.
      Additionally, a new measure of stability is introduced (decorrelation time). The
      application of this measure to the power spectrum is also tested as a cue of
      dysphonia. MATERIALS AND METHODS: The spectral analysis is done having both an
      auditory model and the filterbank approach as references to the computation of
      discrete spectrograms. Results are obtained from three sets of recordings
      belonging to two different databases. RESULTS: The reported results indicate that
      only minor differences exist in the shape of the power spectrum of normal and
      dysphonic voices when performing sustained vowel phonation tasks. However, the
      calculated band power decorrelation times indicate that power in bands between
      2000 and 6400Hz is significantly less stable in dysphonic voices. As for running
      speech, the stability of spectral power is not such a good indicator of
      dysphonia, but there is a significant difference between normal and dysphonic
      voices in the power level of high-frequency bands (above 5300Hz). In addition,
      this means that sampling rates above 10.6ksps are needed for assessing running
      speech in spectral domain. Also, the results involving decorrelation times
      indicate that for short-time spectral analysis, frame rates above 100 frames/s
      should be preferred.

PMID- 23146721
TI  - Effects of endoplasmic reticulum stressors on maturation and signaling of
      hemizygous and heterozygous wild-type and mutant forms of KIT.
AB  - Gain of function mutations of KIT are frequent in some human tumors, and are
      sensible to tyrosine kinase inhibitors. In most tumors, oncogenic mutations are
      heterozygous, however most in vitro data of KIT activation have been obtained
      with hemizygous mutation. This study aimed to investigate the maturation and
      activation of wild-type (WT) and mutant (M) forms of KIT in hemizygous and
      heterozygous conditions. WT and two types of exon 11 deletions M forms of human
      KIT were expressed in NIH3T3 cell lines. Membrane expression of KIT was
      quantified by flow cytometry. Quantification of glycosylated forms of KIT and
      phosphorylated forms of AKT and ERK were performed by western blot. Simultaneous
      activation of WT KIT and treatment with endoplasmic reticulum (ER) inhibitors,
      tunicamycin or brefeldin A induced a complete inhibition of membrane expression
      of the 145 kDa form of KIT. By contrast activation or ER inhibitors alone, only
      partly inhibited this form. ER inhibitors also inhibited KIT activation-dependent
      phosphorylation of AKT and ERK1/2. Brefeldin A induced a complete down regulation
      of the 145 kDa form in hemizygous M, and induced an intra-cellular accumulation
      of the 125 kDa form in WT but not in hemizygous M. Heterozygous cells had
      glycosylation and response to ER inhibitors patterns more similar to WT than to
      hemizygous M. Phosphorylated AKT was reduced in hemizygous cells in comparison to
      WT KIT cells and heterozygous cells, and in the presence of brefeldin A in all
      cell lines. Effects of ER inhibitors are significantly different in hemizygous
      and heterozygous mutants. Differences in intra-cellular trafficking of KIT forms
      result in differences in downstream signaling pathways, and activation of
      PI3K/AKT pathway appears to be tied to the presence of the mature 145 kDa form of
      KIT at the membrane surface.

PMID- 23146722
TI  - Use of cestodes as indicator of heavy-metal pollution.
AB  - Thirty snakehead fish, Channa micropeltes (Cuvier, 1831) were collected at Lake
      Kenyir, Malaysia. Muscle, liver, intestine and kidney tissues were removed from
      each fish and the intestine was opened to reveal cestodes. In order to assess the
      concentration of heavy metal in the environment, samples of water in the surface
      layer and sediment were also collected. Tissues were digested and the
      concentrations of manganese (Mn), zinc (Zn), copper (Cu), cadmium (Cd) and lead
      (Pb) were analysed by using inductively-coupled plasma mass-spectrometry (ICP-MS)
      equipment. The results demonstrated that the cestode Senga parva (Fernando and
      Furtado, 1964) from fish hosts accumulated some heavy metals to a greater extent
      than the water and some fish tissues, but less than the sediment. In three (Pb,
      Zn and Mn) of the five elements measured, cestodes accumulated the highest metal
      concentrations, and in remaining two (Cu and Cd), the second highest metal
      accumulation was recorded in the cestodes when compared to host tissues.
      Therefore, the present study indicated that Senga parva accumulated metals and
      might have potential as a bioindicator of heavy-metal pollution.

PMID- 23146723
TI  - Thrombotic thrombocytopenic purpura in pediatric patients.
AB  - Although thrombotic thrombocytopenic purpura (TTP) is rarely seen in pediatric
      patients, failure to recognize this condition often leads to severe consequences
      and poor outcomes. Classic features of TTP include thrombocytopenia,
      microangiopathic hemolytic anemia, acute kidney injury, fever, and central
      nervous system involvement. However, patients suffering from this condition may
      not present with all of the symptoms simultaneously. Therefore, it is of utmost
      importance for healthcare providers to have a high index of suspicion. Laboratory
      investigations may reveal the presence of schistocytes on peripheral blood smear,
      negative Coombs test, high lactate dehydrogenase levels and severely low platelet
      counts. The etiology of TTP is mainly due to insufficient cleavage of the large
      multimers of von Willebrand factor (vWF) secondary to decreased activity of
      ADAMTS13 (a disintegrin and metalloprotease with Thrombospondin type 1 repeats,
      member 13). TTP can be broadly classified into familial TTP (Upshaw Schulman
      syndrome) and non-familial TTP. Familial TTP is due to a congenital deficiency of
      ADAMTS13. Its mainstay of therapy is initiation of plasmapheresis during the
      acute phase, followed by regular fresh frozen plasma (FFP) infusions.
      Alternatively, non-familial TTP is due to a decrease in ADAMTS13 activity
      secondary to the presence of anti-ADAMTS13 antibodies. Once again, the primary
      treatment is plasmapheresis; however, recent anecdotal data also supports the use
      of rituximab in select cases.

PMID- 23146724
TI  - [Study of genetic susceptibility in 198 children with asthma].
AB  - OBJECTIVE: To analyze the frequency distribution of single nucleotide
      polymorphisms (SNPs) of four asthma-related gene loci (ACE I/D; ADRB2 Arg16Gly;
      TNF-alpha G-308A; MS4A2 Glu237Gly) in 198 asthmatic children, and to investigate
      its association with genetic susceptibility to childhood asthma and some clinical
      phenotypes of asthma. METHODS: Polymerase chain reaction product electrophoresis
      identification and real-time quantitative PCR detecting system were used to
      determine the frequency distributions of the SNPs of the four asthma-related gene
      loci in 198 asthmatic children and 110 healthy controls. The serum total IgE
      (TIgE) levels and blood eosinophil proportion (%EOS) of the asthmatic children
      were measured. Different genotypes at the four asthma-related gene loci were
      compared in terms of TIgE and %EOS. RESULTS: The genotype DD of angiotensin
      converting enzyme (ACE) had a significantly higher frequency in the asthmatic
      children than in the healthy controls (chi2= 30.667, P<0.01), and the frequency
      of D allele was also significantly higher in the asthmatic children than in the
      healthy controls (chi2=7.151, P<0.01). No correlation was found between the
      polymorphism of each gene locus and serum TIgE level and %EOS (P>0.05).
      CONCLUSIONS: Genotype DD of ACE is related to genetic susceptibility to childhood
      asthma and may be the risk factor for childhood asthma.

PMID- 23146725
TI  - [Clinical value of continuous monitoring of fraction of exhaled nitric oxide in
      childhood asthma].
AB  - OBJECTIVE: To investigate changes in the fraction of exhaled nitric oxide (FeNO)
      in childhood asthma, and to evaluate the clinical value of continuous monitoring
      of FeNO. METHODS: Twenty children with mild to moderate asthma were enrolled from
      the special outpatient clinic for asthma. Follow-up was performed at 8, 16, 24,
      32 and 40 weeks after treatment. At each follow-up, asthmatic symptoms were
      recorded, pulmonary function was evaluated and FeNO was measured. RESULTS: The
      mean FeNO decreased rapidly 8 weeks after treatment and slowly afterwards. It
      decreased significantly 8,16,24 and 40 weeks after treatment (P<0.01). It
      increased significantly during acute attacks of asthma and decreased rapidly
      during periods of remission. There was significant negative correlation between
      FeNO and forced expiratory volume in one second (r =-0.193 P<0.05). The receiver
      operating characteristic curve of FeNO showed that FeNO had a sensitivity of
      87.9% and a specificity of 80% for uncontrolled asthma when FeNO was 35.5 ppb,
      and that it had a sensitivity of 97% and a specificity of 27.1% when FeNO was
      20.5 ppb. CONCLUSIONS: monitoring of FeNO can be used to evaluate the control
      level of airway inflammation in childhood asthma. When FeNO is less than 20.5
      ppb, airway inflammation may be well controlled. When FeNO is more than 35.5 ppb,
      airway inflammation may be out of control. A sharp increase in FeNO suggests the
      possibility of acute asthma attack in children.

PMID- 23146726
TI  - [Value of neutrophil CD64 in the diagnosis of community acquired pneumonia in
      children].
AB  - OBJECTIVE: To study the clinical value of the expression of neutrophil surface
      CD64 in the diagnosis of community acquired pneumonia in children. METHODS:
      Ninety-eight children with community acquired pneumonia were recruited into the
      study and were classified into three groups according to pathogene: bacterial
      pneumonia (n=48), viral pneumonia (n=29) and Mycoplasmal pneumonia (n=21). Twenty
      healthy children were enrolled as controls. The bacterial infection group was
      subdivided into mild infection (n=36) and severe infection groups (n=12). The
      levels of peripheral blood neutrophil CD64 were measured using flow cytometry.
      Dynamic changes of C-reactive protein were also detected for each patient.
      RESULTS: The CD64 index and CRP levels in the bacterial pneumonia group were
      significantly higher than in the other three groups (P<0.05). The CD64 index in
      the severe bacterial infection group was significantly higher than in the mild
      group (P<0.05). After antibiotic treatment, expression of CD64 in the severe
      bacterial infection group decreased significantly (P<0.05). The CD64 index was
      positively correlated with CRP value (r=0.545, P<0.01). ROC curve analysis showed
      that the threshold of CD64 and CRP was 2.8 and 8 mg/L respectively. Specificity
      of CD64 index (90%) was much higher than CRP (74%). CONCLUSIONS: The
      determination of peripheral blood neutrophil CD64 contributes to the early
      diagnosis of pulmonary bacterial infection and the evaluation of anti-infection
      effect.

PMID- 23146727
TI  - [Clinical characteristics of Mycoplasma pneumoniae-associated ischemic stroke in
      children, and a literature review].
AB  - OBJECTIVE: To study the clinical characteristics of Mycoplasma pneumoniae (MP)
      associated ischemic stroke in children. METHODS: The case of a girl with MP
      associated ischemic stroke was reported, including clinical manifestations and
      laboratory and imaging examinations, and related literature was reviewed.
      RESULTS: The girl, who was suffering from a respiratory tract infection was found
      to have hemiplegia and aphasia which were expressed in ischemic stroke. IgM
      antibody to MP in serum (1?320) and lavage fluid was positive. Pulmonary imaging
      showed unilateral consolidation and pleural exudate. Cerebral neuroimaging
      examination showed occlusion of the bilateral middle cerebral artery, mainly on
      the left side. The neurological symptoms and signs were recovered after
      comprehensive therapy with medication (azithromycin, hormone and heparin) and
      rehabilitation training. CONCLUSIONS: Ischemic stroke is rare but severe
      manifestation of central nervous system damage in children suffering from MP
      infection. Cerebral imaging and etiological examinations contribute to the
      diagnosis. Early use of macrolide antibiotics, anticoagulant and hormone may
      improve the prognosis.

PMID- 23146728
TI  - [Clinical features and antimicrobial resistance of community-acquired pneumonia
      caused by Klebsiella pneumoniae in infants].
AB  - OBJECTIVE: To study the clinical features and antimicrobial resistance of
      community-acquired pneumonia caused by Klebsiella pneumoniae in infants. METHODS:
      The clinical data of 65 infants with community-acquired pneumonia caused by
      Klebsiella pneumoniae between 2007 and 2011 were retrospectively studied.
      RESULTS: Of the 65 infants, 37 cases (57%) were aged <=3 months, 17 cases (26%)
      over 4 months, 7 cases (11%) over 7 months and 4 cases (6%) between 13 and 24
      months. There were no significant differences in clinical manifestations and
      chest X-ray features between the infants with community-acquired pneumonia caused
      by Klebsiella pneumoniae and those with other bacterial pneumonia. Forty strains
      (62%) of ESBLs-producing Klebsiella pneumoniae were detected. Klebsiella
      pneumoniae was 100% sensitive to imipenem, meropenem and amikacin but resistant
      to penicillins and cephalosporins. The resistance rates of ESBLs-producing
      strains to penicillins, cephalosporins, amoxicillin/clavulanic acid,
      ampicillin/sulbactam, compound sulfamethoxazole, gentamycin, ciprofloxacin and
      aztreonam were significantly higher than for non-ESBLs-producing strains. ESBLs
      producing strains also showed multiple-drug resistance. CONCLUSIONS: Community
      acquired pneumonia caused by Klebsiella pneumoniae is common in infants aged <=3
      months. ESBLs-producing strains are prevalent in community-acquired pneumonia
      caused by Klebsiella pneumoniae and demonstrate both high rates of drug
      resistance and multiple-drug resistance.

PMID- 23146729
TI  - [Monitoring of influenza virus B and clinical features of pediatric pneumonia
      caused by influenza virus B only].
AB  - OBJECTIVE: To investigate the epidemiological features of influenza virus B (IVB)
      in the winter and the clinical features of pediatric pneumonia caused by IVB
      only. METHODS: A retrospective study was performed on the clinical data of
      children with respiratory infection who received pathogen testing and therapy at
      Soochow University Affiliated Children's Hospital during the winters of 2008,
      2009, 2010 and 2011. RESULTS: The positive rates of influenza viruses A and B in
      the winters of 2008, 2009, and 2010 were 0.89%, 5.49%, and 6.24% respectively;
      the positive rate of influenza viruses A and B in the winter of 2011 was 8.72%,
      significantly higher than those in 2008-2010. The positive rates of IVB in the
      winters of 2008, 2009, and 2010 were 0%, 0%, and 0.21% respectively; the positive
      rate of IVB in the winter of 2011 was 5.36%, which was significantly higher than
      in the years 2008 to 2010. Pneumonia caused by IVB was confirmed in 94 children
      during the winter of 2011, including 27 cases of pneumonia caused by IVB only.
      Most of children with pneumonia caused by IVB only were aged over 6 months. The
      common symptoms in the 27 children caused by IVB only were fever (85%), runny
      nose (89%), and cough (100%). Wheezing (26%) and dyspnea (7%) were also seen in
      some cases. Among the 27 children, 19% showed abnormal white blood cell count,
      30% showed increased C-reactive protein, 70% showed decreased prealbumin, and
      none showed visible organ dysfunction. No specific imaging findings were seen in
      the children with pneumonia caused by IVB only. However, many abnormal humoral
      and cellular immunological parameters were found in the majority of these
      children. The average length of hospital stay was approximately one week, there
      were no critical patients and the prognosis was good. CONCLUSIONS: Influenza
      viruses were at a peak level in inpatient children in the winter of 2011. IVB
      infection rate was gradually increasing. In children with pneumonia caused by IVB
      only, there are few critical patients, the symptoms are nonspecific and the
      prognosis is good.

PMID- 23146730
TI  - [Analysis of non-bacterial respiratory pathogen infection in children with
      asthmatic diseases].
AB  - OBJECTIVE: To investigate the association of non-bacterial respiratory pathogens
      with asthmatic diseases in children, and the clinical significance of total serum
      IgE levels and peripheral eosinophil count in infection with non-bacterial
      respiratory pathogens. METHODS: Indirect immunofluorescence assay was used to
      detect IgM antibodies against nine types of non-bacterial respiratory pathogens
      in the sera of 490 children with asthmatic diseases between September 2010 and
      September 2011. Pathogens were analyzed and total serum IgE levels and peripheral
      eosinophil count were measured in IgM-positive cases. RESULTS: Of the 490
      children with asthmatic diseases, 47.6% (233 cases) were positive with IgM
      antibodies against non-bacterial respiratory pathogens, the most common being
      Mycoplasma pneumoniae (MP) (25.3%), followed by adenovirus (ADV) (8.9%) and
      influenza B virus (Flu B) (8.8%). Thirty-six cases suffered from co-infection of
      two or more non-bacterial pathogens, mainly comprising MP and other pathogens
      (94%). There were significant differences in the total detection rate of IgM
      antibodies among all age groups (0-30 days: 50.0%; 1-6 months: 67.3%; 0.5-1 year:
      33.1%; 1-3 years: 57.3%; 3-8.9 years: 61.7%). The positive rate of IgM antibodies
      against respiratory pathogens was highest in children with bronchial asthma,
      followed by children with asthmatic bronchitis, and it was lowest in children
      with bronchiolitis. IgM-positive children had significantly decreased blood
      eosinophils and significantly increased total serum IgE levels. CONCLUSIONS: The
      main non-bacterial respiratory pathogens include MP, ADV and Flu B in children
      with asthmatic diseases, and co-infection of MP and other non-bacterial pathogens
      is common. Infants aged 1 to 6 months have a higher infection rate than other age
      groups. Monitoring the changes in total serum IgE levels and peripheral
      eosinophil count has great significance for the clinical diagnosis and treatment
      of asthmatic diseases in children.

PMID- 23146731
TI  - [Risk factors for periventricular-intraventricular hemorrhage in premature
      infants treated with mechanical ventilation].
AB  - OBJECTIVE: To study risk factors for periventricular-intraventricular hemorrhage
      (PVH-IVH) in premature infants treated with mechanical ventilation. METHODS: A
      total of 205 premature infants who were admitted to the neonatal intensive care
      unit (NICU) and treated with mechanical ventilation between January 2009 and
      December 2011 were enrolled. They were classified into PVH-IVH and non-PVH-IVH
      groups according to the results of head ultrasonography performed at 3 to 7 days
      after birth. Single factor and multivariate logistic regression analysis were
      used to identify risk factors for PVH-IVH. RESULTS: Single factor analysis
      indicated 9 factors associated with the development of PVH-IVH, including a
      gestational age of <32 weeks, a birth weight of <1500 g, intrauterine distress,
      severe asphyxia, vaginal delivery, maternal perinatal infection, premature
      rupture of membranes (PROM) at >=8 hours, mechanical ventilation duration of >=7
      days and ventilator-associated pneumonia (VAP) (P<0.05). Multivariate logistic
      regression analysis showed that a birth weight of <1500 g (OR=2.665),
      intrauterine distress (OR=2.177), severe asphyxia (OR=5.653), maternal perinatal
      infection (OR=4.365) and VAP (OR=2.299) were independent risk factors for the
      development of PVH-IVH (P<0.05). CONCLUSIONS: Very low birth weight, intrauterine
      distress, severe asphyxia, maternal perinatal infection and VAP are closely
      associated with an increased risk of PVH-IVH in premature infants treated with
      mechanical ventilation. These clinical risk factors should be given more
      attention in the prevention of PVH-IVH.

PMID- 23146732
TI  - [Observation of catch-up growth in height within two years of birth in 294
      infants with intrauterine growth retardation].
AB  - OBJECTIVE: To observe catch-up growth in height within two years of birth in
      infants of different sexes, gestational ages, and birth weights with intrauterine
      growth retardation (IUGR). METHODS: Follow-up was performed on 294 IUGR infants
      and 300 healthy full-term infants at 4, 6, 9, 12, 15, 18, 21 and 24 months after
      birth to measure the height, calculate the height increase and compare the two
      groups with respect to height increase. RESULTS: The success rates of catch-up
      growth in height were 72.2% in male infants and 71.5% in female infants (P=0.90),
      and were 77.4% in preterm small-for-gestational age (SGA) infants and 68.6% in
      full-term SGA infants (P=0.11). Success rates of catch-up growth in height in
      infants with birth weights between 1500-2499 g was higher than in those with
      birth weights of <1500 g and >=2500 g (P<0.01). The male infants showed
      significant catch-up growth at 4, 6, 18, 21 and 24 months after birth, while
      significant catch-up growth was found in female infants at 4, 6, 9, 12 and 21
      months after birth. Of the male infants, preterm SGA infants showed significantly
      greater height increase than the full-term SGA infants at 6 and 9 months after
      birth. Of the female infants, preterm SGA infants showed significantly greater
      height increase than the full-term SGA infants at 4 and 18 months after birth.
      For both male and female infants, height increase at 4 months after birth was
      significantly greater in those with birth weights of <1500 g than in those with
      birth weights of >=2500 g. For male infants, height increases at 4, 6, 18, 21 and
      24 months after birth were significantly greater in those with birth weights of
      1500-2499 g than in those with birth weights of >=2500 g. For female infants,
      height increases at 4, 6, 9, 12 and 21 months after birth were significantly
      greater in those with birth weights of 1500-2499 g than in those with birth
      weights of >=2500 g. CONCLUSIONS: The catch-up growth in height within two years
      of birth in infants with IUGR occurs mainly in the first year after birth in
      female infants, but can be seen in the first six months and the second year after
      birth in male infants. Preterm SGA infants better catch-up growth than full-term
      SGA infants, and infants with birth weights of below 1500 g and between 1500-2499
      g show better catch-up growth than those with birth weights of >=2500 g.

PMID- 23146733
TI  - [Clinical features of 39 children with head and neck rhabdomysarcoma in a single
      medical center, and treatment outcomes].
AB  - OBJECTIVE: To study the clinical features and treatment outcomes of head and neck
      rhabdomysarcoma (RMS) in children. METHODS: The clinical data and results of
      follow-up visits for 39 children with head and neck RMS were retrospectively
      reviewed. The children (23 males and 16 females) with a median age of 6 years old
      (ranged 3 months to 14 years) were admitted to the Beijing Tongren Hospital
      between November, 2004 and November, 2010. RESULTS: The 39 children mainly
      presented with exophthalmos and eyelid swelling (56%, 22/39), rhinostegnosis and
      nasal bleeding (28%, 11/39) and check mass (15%, 6/39). Common primary sites were
      the eyelid and orbit (56%, 22/39), followed by the nasopharynx and ethmoid antrum
      (28%, 11/39). Thirty-seven of the 39 patients showed a definite pathologic type
      and the embryo type was the most common (89%, 33/37). Follow-up visits were
      carried out for 35 children, with a median follow-up time of 38 months (10-80
      months). Of the 35 children, 4 cases received surgery alone, 1 case received
      chemotherapy alone, 12 cases received surgery plus chemotherapy, 2 cases received
      surgery plus radiochemotherapy, 13 cases received surgery, chemotherapy and
      radiochemotherapy (8 cases received 125I particles implants), 2 cases received
      surgery, chemotherapy, radiochemotherapy and autologous peripheral blood stem
      cells transplantation (APBSCT), and 1 case received chemotherapy and APBSCT.
      Seven cases relapsed and 5 cases died of brain metastasis. The total survival
      rate was 86% (30/35), the complete remission rate was 66% (23/35), and the
      partial remission rate was 20%. In the 8 cases receiving 125I particles implants,
      6 survived without tumor. CONCLUSIONS: Exophthalmos and eyelid swelling are the
      main presentations in children with head and neck RMS. Common primary sites of
      this disease are the eye and nasopharynx. The most common pathologic type is
      embryo type. Comprehensive treatment, including chemotherapy, surgery, 125I
      particles implants and APBSCT therapy, can improve outcome.

PMID- 23146734
TI  - [Adverse effects of methotrexate in the treatment of acute lymphoblastic leukemia
      in Uyghur and Han children].
AB  - OBJECTIVE: To study blood concentrations of methotrexate (MTX) in Uyghur and Han
      children with acute lymphoblastic leukemia (ALL), and to provide criteria for
      judging the incidence of adverse effects of MTX. METHODS: Twenty-eight children
      with ALL (15 Han children and 13 Uyghur children), who received high-dose MTX
      chemotherapy, were divided into >10 MUmol/L and <=10 MUmol/L groups according to
      24-hour blood concentration of MTX, and divided into >1.0 MUmol/L and <=1.0
      MUmol/L groups according to 48-hour blood concentration of MTX. Enzyme multiplied
      immunoassay was used to measure blood concentrations of MTX in the MTX-treated
      children at 24 and 48 hours after MTX administration, and the adverse effects
      were observed. RESULTS: There was no significant difference in the incidence of
      adverse effects between the >10 MUmol/L and <=10 MUmol/L groups (P>0.05). The
      >1.0 MUmol/L group showed higher incidences of gastrointestinal reactions and
      mucosal injuries than the <=1.0 MUmol/L group (P<0.05), but no significant
      difference was found between the two groups with respect to the incidence of
      abnormal liver function and bone marrow suppression (P>0.05). Compared with
      Uyghur children, Han children showed higher 24- and 48-hour blood concentrations
      of MTX (P<0.05) and higher incidence of abnormal liver function, mucosal
      injuries, and bone marrow suppression (P<0.05). CONCLUSIONS: The 24-hour blood
      concentration of MTX cannot be used to predict the incidence of adverse effects
      in MTX chemotherapy, but 48-hour blood concentration of MTX is helpful in this
      regard. There are significant differences in 24- and 48-hour blood concentrations
      of MTX and the incidence of adverse effects between Uyghur and the Han children
      with ALL who receive MTX chemotherapy. Monitoring of blood MTX concentration
      maybe significant for timely adjustment of MTX dosage and individualized MTX
      chemotherapy.

PMID- 23146735
TI  - [Clinical and molecular genetic analysis for a patient with glycogen storage
      disease Ia].
AB  - OBJECTIVE: To investigate the mutation of glucose-6-phosphatase gene (G6PC gene)
      in a patient with glycogen storage disease Ia. METHODS: PCR was used to amplify
      all five exons of G6PC gene. The PCR products were directly sequenced to detect
      the mutations. RESULTS: A heterozygous 743G>A mutation was found in the patient
      and his mother, resulting in the substitution of glycine (G) by arginine (R) in
      codon 222(G222R) in the putative membrane-spanning domain in human G6Pase, but
      not in his father and his sister. CONCLUSIONS: G222R mutation in G6PC gene was
      first identified in a patient with glycogen storage disease Ia in mainland China.

PMID- 23146736
TI  - [Clinical application of flexible bronchoscopy and balloon dilatation in
      pediatric respiratory diseases under local anesthesia].
AB  - OBJECTIVE: To study the significance and safety of flexible bronchoscopy and
      balloon dilatation in the diagnosis and treatment of respiratory diseases in
      children. METHODS: A total of 438 children (236 males and 202 females) with
      respiratory diseases who were aged from 17 days to 15 years, were examined and/or
      treated by bronchoscopy (including bronchoscopic intervention) under local
      anesthesia. RESULTS: Of the 438 children, 311 were diagnosed with pulmonary
      infection, 68 with atelectasis, 36 with recurrent cough and asthma, 6 with
      hemoptysis of unknown origin, 6 with bronchial foreign body, 5 with congenital
      bronchopulmonary dysplasia, 2 with bronchiectasis, 1 with ciliary dyskinesia
      syndrome, 1 with lung tumor, and 2 with congenital immunodeficiency disease.
      After bronchoscopic examination, local flushing or bronchoalveolar lavage, and
      foreign body extraction, marked response was seen in 379 cases and response was
      seen in 46 cases. High-pressure balloon dilatation under bronchoscopy was
      performed in 5 cases with inflammatory stricture and achieved satisfying clinical
      effect. No severe complications were found in bronchoscopy. CONCLUSIONS:
      Bronchoscopy and balloon dilatation under local anesthesia is safe and effective
      for the diagnosis and treatment of respiratory diseases in children.

PMID- 23146737
TI  - [Expression of RANTES in the lung tissue of asthmatic rats, and the intervention
      effect of vitamin D on RANTES expression].
AB  - OBJECTIVE: To investigate the effect of vitamin D on the expression of chemokine
      regulated on activation, normal T cells expressed and secreted (RANTES) in the
      lung tissue of asthmatic rats, and the role of vitamin D in the control of
      asthmatic airway inflammation and the synergistic action of hormones. METHODS:
      Forty female Wistar rats were randomly and equally divided into normal control,
      asthma, vitamin D intervention, budesonide intervention, and budesonide+vitamin D
      intervention groups. Hematoxylin and eosin staining was used to observe
      pathological changes in the lung tissue. Immunohistochemistry was used to measure
      the protein expression of RANTES in lung tissue. Enzyme-linked immunosorbent
      assay was used to measure the level of RANTES in bronchoalveolar lavage fluid
      (BALF). Real-time quantitative PCR was used to measure the mRNA expression of
      RANTES. RESULTS: The asthma group showed the most significant pathological
      changes in the lung tissue, including inflammatory cell infiltration, bronchial
      stenosis and distortion and smooth muscle rupture, while the intervention groups
      showed fewer pathological changes. Of the intervention groups, the budesonide
      intervention group showed fewer pathological changes than the vitamin D
      intervention group, and the budesonide+vitamin D intervention group showed the
      mildest pathological changes, which were similar to those observed in the normal
      control group. Protein expression of RANTES in the lung tissue and BALF was
      significantly higher in the asthma group than in the normal control group
      (P<0.05), while it was lower in the intervention groups than in the asthma group,
      exhibiting significant differences between each intervention group and the asthma
      group (P<0.05) (except the difference in protein expression of RANTES in BALF
      between the vitamin D intervention and asthma groups). The budesonide+vitamin D
      intervention group showed less protein expression of RANTES in the lung tissue
      and BALF than both the budesonide intervention and vitamin D intervention groups
      (P<0.05). The mRNA expression of RANTES was significantly higher in the asthma
      group than in the normal control group (P<0.05), while it was significantly lower
      in three intervention groups than in the asthma group (P<0.05), however no
      significant difference was found between the intervention groups in this regard.
      The budesonide+vitamin D intervention group showed the lowest level of RANTES
      mRNA, with no significant difference from the normal control group. CONCLUSIONS:
      The mRNA and protein expression of RANTES in BALF and lung tissue increases
      significantly in asthmatic rats. Vitamin D intervention can decrease the
      expression of RANTES, suggesting that vitamin D can reduce airway inflammation by
      regulating the expression of RANTES. Vitamin D can be used together with
      budesonide to further decrease the mRNA and protein expression of RANTES.

PMID- 23146738
TI  - [Changes in expression levels of PV, GAD67 and KCC2 in the brain tissue of rats
      with schizophrenia induced by MK-801].
AB  - OBJECTIVE: To study changes in the expression levels of parvalbumin (PV),
      glutamate decarboxylase 67 (GAD67) and K+-Cl- cotransporter 2 (KCC2) in the brain
      tissue of rats with schizophrenia (SZ) induced by dizocilpine (MK-801), and to
      investigate the mechanism involving gamma-aminobutyric acid (GABA) by which NMDA
      receptor blocker induces SZ in the perinatal period. METHODS: Thirty-six neonatal
      male Sprague-Dawley rats were randomly assigned to two batches on postnatal day
      6. Each batch was divided into normal control (treated by 0.9% normal saline), SZ
      development model (treated by subcutaneous injection of 0.1 mg/kg MK-801 on
      postnatal days 7-10; bid), and SZ-chronic medication model groups (treated by
      intraperitoneal injection of 0.2 mg/kg MK-801 on postnatal days 47-60; qd). On
      postnatal day 63, the brain tissue of the first batch of rats was obtained and
      then fixed with paraform for histological sections; expression levels of PV and
      GAD67 in the medial prefrontal cortex (mPFC) and hippocampus CA1 were measured by
      immunohistochemistry. Simultaneously, the second batch of rats was sacrificed and
      the mPFC and hippocampus were obtained and homogenized; expression levels of KCC2
      in the mPFC and hippocampus were measured by Western blot. RESULTS: Expression
      levels of PV and GAD67 in the mPFC and hippocampus CA1 were significantly lower
      in the SZ-development and chronic medication model groups than in the normal
      control group (P<0.05). Expression levels of KCC2 in the mPFC and hippocampus
      were significantly lower in the SZ-development model group than in the SZ-chronic
      medication model and normal control groups (P<0.05). CONCLUSIONS: The expression
      changes of PV and GAD67 in SZ can be simulated using the SZ development model
      induced by MK-801, which might affect the development of the GABA system in the
      PFC and hippocampus by downregulating KCC2 expression.

PMID- 23146739
TI  - [Clinical features and prognosis of pediatric multiple sclerosis].

PMID- 23146740
TI  - [A case of malonyl-CoA decarboxylase deficiency: clinical and genetic study].

PMID- 23146741
TI  - [Alice-in-Wonderland syndrome as first presentation of migraine in a child].

PMID- 23146742
TI  - In vitro brown and "brite"/"beige" adipogenesis: human cellular models and
      molecular aspects.
AB  - Brown adipose tissue (BAT) has long been thought to be absent or very scarce in
      human adults so that its contribution to energy expenditure was not considered as
      relevant. The recent discovery of thermogenic BAT in human adults opened the
      field for innovative strategies to combat overweight/obesity and associated
      diseases. This energy-dissipating function of BAT is responsible for adaptive
      thermogenesis in response to cold stimulation. In this context, adipocytes can be
      converted, within white adipose tissue (WAT), into multilocular adipocytes
      expressing UCP1, a mitochondrial protein that plays a key role in heat production
      by uncoupling the activity of the respiratory chain from ATP synthesis. These
      adipocytes have been named "brite" or "beige" adipocytes. Whereas BAT has been
      studied for a long time in murine models both in vivo and in vitro, there is now
      a strong demand for human cellular models to validate and/or identify critical
      factors involved in the induction of a thermogenic program within adipocytes. In
      this review we will discuss the different human cellular models described in the
      literature and what is known regarding the regulation of their differentiation
      and/or activation process. In addition, the role of microRNAs as novel regulators
      of brown/"brite" adipocyte differentiation and conversion will be depicted.
      Finally, investigation of both the conversion and the metabolism of white-to
      brown converted adipocytes is required for the development of therapeutic
      strategies targeting overweight/obesity and associated diseases. This article is
      part of a Special Issue entitled Brown and White Fat: From Signaling to Disease.

PMID- 23146743
TI  - The trans effect of nitroxyl (HNO) in ferrous heme systems: implications for
      soluble guanylate cyclase activation by HNO.
AB  - Soluble guanylate cyclase (sGC) is the primary mammalian nitric oxide (NO)
      sensor. Through the strong thermodynamic sigma-trans effect of NO, binding of NO
      at the distal side of the ferrous heme induces cleavage of the proximal FeN(His)
      bond, activating the catalytic domain of the enzyme. It has been proposed that
      nitroxyl (HNO) is also capable of activating sGC, but the key question remains as
      to whether HNO can induce cleavage of the FeN(His) bond. Here we report
      calculated binding constants for 1-methylimidazole (MI) to [Fe(P)(X)]
      (P=porphine(2-)) where X=NO, HNO, CO, and MI to evaluate the trans interaction of
      these groups, X, with the proximal imidazole (histidine) in sGC. Systematic
      assessment of DFT methods suggests that the prediction of accurate MI binding
      constants is critically dependent on the inclusion of van der Waals interactions
      (-D functionals). Calculated (B3LYP-D/TZVP) MI binding constants for X=NO and MI
      are 110 and 5.6 * 10(5)M(-1), respectively, predicted only one order of magnitude
      higher than the corresponding experimentally determined values. MI binding
      constants where X=HNO and CO are consistently predicted to be essentially equal
      and ~six orders of magnitude larger than those of NO, indicating that CO and HNO
      mediate a weak thermodynamic trans effect in this system. Orbital analysis of the
      key sigma-bonding orbital, pi*(h)_d(z2), and comparison of FeN(MI) bond lengths
      support this prediction. This suggests that HNO does not induce a sigma-trans
      effect strong enough to promote cleavage of the FeN(His) bond-a key step in the
      activation of sGC.

PMID- 23146744
TI  - A randomized controlled trial to evaluate the effectiveness of CouPLES: a spouse
      assisted lifestyle change intervention to improve low-density lipoprotein
      cholesterol.
AB  - OBJECTIVE: This randomized controlled trial evaluated the effectiveness of a
      telephone-delivered, spouse-assisted lifestyle intervention to reduce patient LDL
      C. METHOD: From 2007 to 2010, 255 outpatients with LDL-C>76 mg/dL and their
      spouses from the Durham Veterans Affairs Medical Center were randomized to
      intervention or usual care. The intervention comprised nine monthly goal-setting
      telephone calls to patients and support planning calls to spouses. Outcomes were
      assessed at 11 months. RESULTS: Patients were 95% male and 65% White. LDL-C did
      not differ between groups (mean difference = 2.3 mg/dL, 95% CI = -3.6, 8.3, p =
      0.44), nor did the odds of meeting goal LDL-C (OR = 0.95, 95% CI = 0.6, 1.7; p =
      0.87). Intakes of calories (p = 0.03), total fat (p = 0.02), and saturated fat (p
      = 0.02) were lower for the intervention group. Cholesterol and fiber intake did
      not differ between groups (p = 0.11 and 0.26, respectively). The estimated rate
      of moderate intensity physical activity per week was 20% higher in the
      intervention group (IRR = 1.2, 95% CI = 1.0, 1.5, p = 0.06). Most participants
      did not experience a change in cholesterol medication usage during the study
      period in the intervention (71.7%) and usual care (78.9%) groups. CONCLUSION:
      This intervention might be an adjunct to usual primary care to improve adherence
      to lifestyle behaviors.

PMID- 23146745
TI  - [Treatment of the tubo-ovarian abscesses].
AB  - The antibiotic treatment is indispensable for the treatment of the tubo-ovarian
      abscesses (TOA). It has to have a wide spectre and would be secondarily adapted
      in case of a sexually transmitted infection. The surgery remains indicated in
      first intention in case of vital threat (generalized peritonitis, toxic shock).
      In the not complicated TOA, the evacuation of abscesses (by draining under
      imaging or laparoscopy) with the antibiotic treatment gives better rates of cure
      than the antibiotic treatment alone. For the surgery, several entrys are
      possible. The laparoscopy allows a shorter hospitalization with fewer
      complications and a faster resolution of the fever than the laparotomy. The
      conservative surgery, realized by laparoscopy, has hight rates of successes with
      few complications. The radical surgery, by coelioscopy or by laparotomy, has high
      rates of complications. Transvaginal ultrasound guided aspiration is an
      alternative in the drainage by laparscopy with identical succes. It has been well
      evaluated. It has low morbidity and can be proposed in first intention in not
      complicated TOA.

PMID- 23146746
TI  - Is thyroid screening of sleep clinic patients essential?

PMID- 23146747
TI  - Development of scales for assessment of rapid eye movement sleep behavior
      disorder (RBD).
AB  - Rapid eye movement (REM) sleep behavior disorder (RBD) is characterized by an
      absence of normal skeletal muscle atonia during REM sleep and clinical features
      of disturbing dreams and dream enacting behaviors. Hence, the common sequelae are
      sleep-related injury and violence to both patients and bed-partners. Although
      polysomnographic evidence of REM sleep without atonia, is regarded as a gold
      standard for the confirmation of RBD diagnosis, polysomnography is both time and
      resource consuming. In order to facilitate early detection and clinical
      management, developing a convenient and suitable screening tool to identify
      individuals at risk of RBD would enable physicians to prioritize those who may
      require timely assessment and clinical intervention. In addition, the
      longitudinal course of RBD and its prognostic implication in predicting
      neurodegenerative disorders may suggest a potential therapeutic window for early
      preventive management of underlying progress of neurodegeneration. The
      availability of suitable RBD scales may facilitate timely assessment, accurate
      diagnosis and monitoring of disease progress of RBD. The present paper summarized
      recent research on the development of screening tools of RBD, their psychometric
      properties, and the applications of these questionnaires. 

PMID- 23146748
TI  - Decreased levels of AKR1B1 and AKR1B10 in cancerous endometrium compared to
      adjacent non-cancerous tissue.
AB  - Endometrial cancer is associated with enhanced cell proliferation due to high
      concentrations of estrogens, and decreased cell differentiation due to low levels
      of progesterone and retinoic acid. It is also associated with aberrant
      inflammatory responses and concomitant increased production of prostaglandins.
      The human members of the aldo-keto reductase 1B (AKR1B) subfamily, AKR1B1 and
      AKR1B10, have roles in these processes and can thus be implicated in endometrial
      cancer. To date, there have been no reports on the expression of AKR1B1 in
      endometrial cancer, while AKR1B10 has only been studied at the cellular level. To
      evaluate the roles of these AKR1B enzymes, we investigated expression of AKR1B1
      and AKR1B10 in 47 paired samples of cancerous and adjacent control endometrium at
      the mRNA and protein levels, by quantitative PCR, Western blotting and
      immunohistochemistry staining. There were significantly lower mRNA and protein
      levels of AKR1B1 in cancerous tissues compared to adjacent endometrium. The gene
      expression of AKR1B10 at the mRNA level was significantly increased, while there
      were significantly decreased protein levels. Immunohistochemistry revealed that
      both of these enzymes were present in all of the samples, and are located in
      epithelial cells of cancerous and control endometrial glands. Elevated levels in
      adjacent non-cancerous tissues imply that these enzymes are more important in the
      initiation of endometrial cancer than in its progression. To the best of our
      knowledge, this is the first report on the expression of AKR1B1 and AKR1B10 in
      endometrial cancer. Further studies are needed to define the precise roles of
      these enzymes in the pathogenesis of endometrial cancer.

PMID- 23146750
TI  - Cultured human peripheral blood mononuclear cells alter their gene expression
      when challenged with endocrine-disrupting chemicals.
AB  - Endocrine disrupting chemicals (EDCs) have the potential to interfere with the
      hormonal system and may negatively influence human health. Microarray analysis
      was used in this study to investigate differential gene expression in human
      peripheral blood cells (PBMCs) after in vitro exposure to EDCs. PBMCs, isolated
      from blood samples of four male and four female healthy individuals, were exposed
      in vitro for 18h to either a dioxin-like polychlorinated biphenyl (PCB126, 1MUM),
      a non-dioxin-like polychlorinated biphenyl (PCB153, 10MUM), a brominated flame
      retardant (BDE47, 10MUM), a perfluorinated alkyl acid (PFOA, 10MUM) or bisphenol
      (BPA, 10MUM). ANOVA analysis revealed a significant change in the expression of
      862 genes as a result of EDC exposure. The gender of the donors did not affect
      gene expression. Hierarchical cluster analysis created three groups and
      clustered: (1) PCB126-exposed samples, (2) PCB153 and BDE47, (3) PFOA and BPA.
      The number of differentially expressed genes varied per compound and ranged from
      60 to 192 when using fold change and multiplicity corrected p-value as filtering
      criteria. Exposure to PCB126 induced the AhR signaling pathway. BDE47 and PCB153
      are known to disrupt thyroid metabolism and exposure influenced the expression of
      the nuclear receptors PPARgamma and ESR2, respectively. BPA and PFOA did not
      induce significant changes in the expression of known nuclear receptors. Overall,
      each compound produced a unique gene expression signature affecting pathways and
      GO processes linked to metabolism and inflammation. Twenty-nine genes were
      significantly altered in expression under all experimental conditions. Six of
      these genes (HSD11B2, MMP11, ADIPOQ, CEL, DUSP9 and TUB) could be associated with
      obesity and metabolic syndrome. In conclusion, microarray analysis identified
      that PBMCs altered their gene expression response in vitro when challenged with
      EDCs. Our screening approach has identified a number of gene candidates that
      warrant further study.

PMID- 23146749
TI  - ALOG domains: provenance of plant homeotic and developmental regulators from the
      DNA-binding domain of a novel class of DIRS1-type retroposons.
AB  - Members of the Arabidopsis LSH1 and Oryza G1 (ALOG) family of proteins have been
      shown to function as key developmental regulators in land plants. However, their
      precise mode of action remains unclear. Using sensitive sequence and structure
      analysis, we show that the ALOG domains are a distinct version of the N-terminal
      DNA-binding domain shared by the XerC/D-like, protelomerase, topoisomerase-IA,
      and Flp tyrosine recombinases. ALOG domains are distinguished by the insertion of
      an additional zinc ribbon into this DNA-binding domain. In particular, we show
      that the ALOG domain is derived from the XerC/D-like recombinases of a novel
      class of DIRS-1-like retroposons. Copies of this element, which have been
      recently inactivated, are present in several marine metazoan lineages, whereas
      the stramenopile Ectocarpus, retains an active copy of the same. Thus, we predict
      that ALOG domains help establish organ identity and differentiation by binding
      specific DNA sequences and acting as transcription factors or recruiters of
      repressive chromatin. They are also found in certain plant defense proteins,
      where they are predicted to function as DNA sensors. The evolutionary history of
      the ALOG domain represents a unique instance of a domain, otherwise exclusively
      found in retroelements, being recruited as a specific transcription factor in the
      streptophyte lineage of plants. Hence, they add to the growing evidence for
      derivation of DNA-binding domains of eukaryotic specific TFs from mobile and
      selfish elements.

PMID- 23146751
TI  - Perinatal exposure to lead induces morphological, ultrastructural and molecular
      alterations in the hippocampus.
AB  - The aim of this paper is to examine if pre- and neonatal exposure to lead (Pb)
      may intensify or inhibit apoptosis or necroptosis in the developing rat brain.
      Pregnant experimental females received 0.1% lead acetate (PbAc) in drinking water
      from the first day of gestation until weaning of the offspring; the control group
      received distilled water. During the feeding of pups, mothers from the
      experimental group were still receiving PbAc. Pups were weaned at postnatal day
      21 and the young rats of both groups then received only distilled water until
      postnatal day 28. This treatment protocol resulted in a concentration of Pb in
      rat offspring whole blood (Pb-B) below the threshold of 10 MUg/dL, considered
      safe for humans.We studied Casp-3 activity and expression, AIF nuclear
      translocation, DNA fragmentation, as well as Bax, Bcl-2 mRNA and protein
      expression as well as BDNF concentration in selected structures of the rat brain:
      forebrain cortex (FC), cerebellum (C) and hippocampus (H). The microscopic
      examinations showed alterations in hippocampal neurons.Our data shows that pre-
      and neonatal exposure of rats to Pb, leading to Pb-B below 10 MUg/dL, can
      decrease the number of hippocampus neurons, occurring concomitantly with
      ultrastructural alterations in this region. We observed no morphological or
      molecular features of severe apoptosis or necrosis (no active Casp-3 and AIF
      translocation to nucleus) in young brains, despite the reduced levels of BDNF.
      The potential protective factor against apoptosis was probably the decreased
      Bax/Bcl-2 ratio, which requires further investigation. Our findings contribute to
      further understanding of the mechanisms underlying Pb neurotoxicity and cognition
      impairment in a Pb-exposed developing brain.

PMID- 23146752
TI  - Chlorogenic acid reduces liver inflammation and fibrosis through inhibition of
      toll-like receptor 4 signaling pathway.
AB  - Chlorogenic acid (CGA) is a type of polyphenol with anti-inflammatory,
      antioxidant activities. Our previous studies showed CGA could efficiently inhibit
      carbon tetrachloride (CCl(4))-induced liver fibrosis in rats. However, the
      specific underlying mechanism remains unclear. The aim of this study is to
      investigate the effects of CGA on liver inflammation and fibrosis induced by
      CCl(4) and whether they are related to inhibition of toll-like receptor 4 (TLR4)
      signaling pathway. Male Sprague-Dawley (SD) rats were administrated CCl(4)
      together with or without CGA for 8 weeks. Histopathological and biochemical
      analyses were carried out. The mRNA and protein expression levels of
      proinflammatory and profibrotic mediators were detected by RT-PCR and Western
      blot, respectively. The levels of serum proinflammatory cytokines were detected
      by ELISA. CGA significantly attenuated CCl(4)-induced liver damage and symptoms
      of liver fibrosis, accompanied by reduced serum transaminase levels, collagen I
      and alpha-smooth muscle actin (alpha-SMA) expression. As compared with the CCl(4)
      treated group, the expression levels of TLR4, myeloid differentiation factor 88
      (MyD88), inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) were
      reduced in the treatment group of CCl(4) and CGA, whereas bone morphogenetic
      protein and activin membrane-bound inhibitor (Bambi) expression was increased.
      CGA also suppressed CCl(4) induced nuclear factor-kappaB (NF-kappaB) activation.
      Moreover, the hepatic mRNA expression and serum levels of tumor necrosis factor
      alpha (TNF-alpha), interleukin-6 (IL-6) and interleukin-1beta (IL-1beta) were
      significantly increased in CCl(4)-treated rats and attenuated by co-treatment
      with CGA. Our data indicate that CGA can efficiently inhibit CCl(4)-induced liver
      fibrosis in rats and the protective effect may be due to the inhibition of
      TLR4/MyD88/NF-kappaB signaling pathway.

PMID- 23146753
TI  - International experience in addressing combined exposures: increasing the
      efficiency of assessment.
AB  - More efficient methodology for assessing the impact of combined exposures to
      multiple chemicals has been considered in a project of the World Health
      Organization (WHO) International Programme on Chemical Safety (IPCS).
      Recommendations regarding terminology and the status of development of the
      framework, its content, review and application are described. Evolving experience
      in its application is illustrated by example (polybrominated diphenyls) with
      special emphasis on the critical content of problem formulation, the role of
      predictive tools in grouping of chemicals for consideration and the importance of
      explicit delineation of relative uncertainty and sensitivity for tiered
      assessment. Priorities in increasing the efficiency of risk assessment not only
      for combined exposures, but more generally based on experience acquired in
      developing the framework and its application in case studies are identified and
      recommendations included. 

PMID- 23146754
TI  - Effects of arsenite in astrocytes on neuronal signaling transduction.
AB  - The main purpose of this study was to test the hypothesis that arsenite induces
      neurotoxicity via effects on astrocytes. Astrocytes were exposed to 0, 5 or 10
      MUM arsenite in medium for 24 h, and then astrocyte-conditioned medium (ACM) was
      collected after incubation with fresh medium for 6 h. Primary neuron cultures
      were divided into four groups due to ACM, which were neurons without ACM exposure
      (group I) and neurons exposed to ACM from 0, 5 or 10 MUM arsenite treated
      astrocytes (group II-IV). Protein expression of N-methyl-d-aspartate receptors
      (NR1, NR2A, NR2B), calmodulin-dependent protein kinase II (CaMKII) and adenylate
      cyclase (AC) in neurons were measured after incubation with ACM for 4, 8 or 12 h.
      Morphological changes and synaptic formation were observed after a 72 h
      incubation with ACM. Compared to group II, synaptic formation and protein
      expression of NR2A, NR2B, CaMKII and AC in group III and IV were significantly
      suppressed. Moreover, synaptic formation and protein expression of CaMKII and AC
      in group II were significantly enhanced when compared with group I. Taken
      together, findings from this study suggested that arsenic in astrocytes might
      impair synaptic formation through disturbing astrocytic effects on neuronal
      signal transduction.

PMID- 23146755
TI  - The mechanism of carvacrol-evoked [Ca2+]i rises and non-Ca2+-triggered cell death
      in OC2 human oral cancer cells.
AB  - Carvacrol is one of the main substances of essential oil which triggers
      intracellular Ca(2+) mobilization and causes cytotoxicity in diverse cell models.
      However, the mechanism of carvacrol-induced Ca(2+) movement and cytotoxicity is
      not fully understood. This study examined the effect of carvacrol on cytosolic
      free Ca(2+) concentrations ([Ca(2+)](i)), cell viability and apoptosis in OC2
      human oral cancer cells. Carvacrol induced a [Ca(2+)](i) rise and the signal was
      reduced by removal of extracellular Ca(2+). Carvacrol-induced Ca(2+) entry was
      not altered by store-operated Ca(2+) channel inhibitors and protein kinase C
      (PKC) activator, but was inhibited by a PKC inhibitor. In Ca(2+) -free medium,
      treatment with the endoplasmic reticulum Ca(2+) pump inhibitor thapsigargin (TG)
      or 2,5-di-tert-butylhydroquinone (BHQ) inhibited carvacrol-induced [Ca(2+)](i)
      rise. Conversely, incubation with carvacrol inhibited TG or BHQ-induced
      [Ca(2+)](i) rise. Inhibition of phospholipase C (PLC) with U73122 abolished
      carvacrol-induced [Ca(2+)](i) rise. Carvacrol decreased cell viability, which was
      not reversed when cytosolic Ca(2+) was chelated with BAPTA-AM (1,2-bis(2
      aminophenoxy)ethane-N,N,N',N'-tetraacetic acid-acetoxymethyl ester). Carvacrol
      induced apoptosis and activation of reactive oxygen species (ROS) and caspase-3.
      Together, carvacrol induced a [Ca(2+)](i) rise by inducing PLC-dependent Ca(2+)
      release from the endoplasmic reticulum and Ca(2+) entry via PKC-sensitive, non
      store-operated Ca(2+) channels. Carvacrol-induced ROS- and caspase-3-associated
      apoptosis.

PMID- 23146756
TI  - Toxicity of the synthetic polymeric 3-alkylpyridinium salt (APS3) is due to
      specific block of nicotinic acetylcholine receptors.
AB  - The in vivo and in vitro toxic effects of the synthetic polymeric 3
      alkylpyridinium salt (APS3), from the Mediterranean marine sponge Reniera sarai,
      were evaluated on mammals, with emphasis to determine its mode of action. The
      median lethal doses of APS3 were 7.25 and higher that 20mg/kg in mouse and rat,
      respectively. Intravenous administration of 7.25 and 20mg/kg APS3 to rat caused a
      significant fall followed by an increase in mean arterial blood pressure
      accompanied by tachycardia. In addition, cumulative doses of APS3 (up to 60
      mg/kg) inhibited rat nerve-evoked skeletal muscle contraction in vivo, with a
      median inhibitory dose (ID(50)) of 37.25mg/kg. When administrated locally by
      intramuscular injection to mouse, APS3 decreased the compound muscle action
      potential recorded in response to in vivo nerve stimulation, with an ID(50) of
      0.5mg/kg. In vitro experiments confirmed the inhibitory effect of APS3 on mouse
      hemidiaphragm nerve-evoked muscle contraction with a median inhibitory
      concentration (IC(50)) of 20.3 MUM, without affecting directly elicited muscle
      contraction. The compound inhibited also miniature endplate potentials and nerve
      evoked endplate potentials with an IC(50) of 7.28 MUM in mouse hemidiaphragm.
      Finally, APS3 efficiently blocked acetylcholine-activated membrane inward
      currents flowing through Torpedo nicotinic acetylcholine receptors (nAChRs)
      incorporated to Xenopus oocytes, with an IC(50) of 0.19 MUM. In conclusion, our
      results strongly suggest that APS3 blocks muscle-type nAChRs, and show for the
      first time that in vivo toxicity of APS3 is likely to occur through an antagonist
      action of the compound on these receptors.

PMID- 23146757
TI  - Mixtures research at NIEHS: an evolving program.
AB  - The National Institute of Environmental Health Sciences (NIEHS) has a rich
      history in evaluating the toxicity of mixtures. The types of mixtures assessed by
      the Division of the National Toxicology Program (DNTP) and the extramural
      community (through the Division of Extramural Research and Training, DERT) have
      included a broad range of chemicals and toxicants, with each study having a
      unique set of questions and design considerations. Some examples of the types of
      mixtures studied include: groundwater contaminants, pesticides/fertilizers,
      dioxin-like chemicals (assessing the toxic equivalency approach), drug
      combinations, air pollution, metals, polycyclic aromatic hydrocarbons, technical
      mixtures (e.g., pentachlorophenol, flame retardants), and mixed entities (e.g.,
      herbals, asbestos). These endeavors have provided excellent data on the toxicity
      of specific mixtures and have been informative to the human health risk
      assessment process in general (e.g., providing data on low dose exposures to
      environmental chemicals). However, the mixtures research effort at NIEHS, to
      date, has been driven by test article nominations to the DNTP or by investigator
      initiated research through DERT. Recently, the NIEHS has embarked upon an effort
      to coordinate mixtures research across both intramural and extramural divisions
      in order to maximize mixtures research results. A path forward for NIEHS mixtures
      research will be based on feedback from a Request for Information (RFI) designed
      to gather up-to-date views on the knowledge gaps and roadblocks to evaluating
      mixtures and performing cumulative risk assessment, and a workshop organized to
      bring together mixtures experts from risk assessment, exposure science, biology,
      epidemiology, and statistics. The future of mixtures research at NIEHS will
      include projects from nominations to DNTP, studies by extramural investigators,
      and collaborations across government agencies that address high-priority
      questions in the field of mixtures research. 

PMID- 23146758
TI  - The 2,2',4,4'-tetrabromodiphenyl ether hydroxylated metabolites 5-OH-BDE-47 and 6
      OH-BDE-47 stimulate estradiol secretion in the ovary by activating aromatase
      expression.
AB  - The aim of the present study was to assess the effect of two hydroxylated BDE-47
      metabolites, 5-OH-BDE-47 and 6-OH-BDE-47, on steroidogenesis in the ovary. Both
      metabolites failed to affect the production of androstenedione and testosterone
      but increased the secretion of estradiol at all concentrations tested. The
      increased secretion of estradiol was due to the stimulation of aromatase gene and
      protein expression. Direct assessment of aromatase activity by
      dibenzylfluorescein assay and indirect assessment of aromatase activity by
      measurement of the conversion of testosterone to estradiol confirmed that 5-OH
      BDE-47 and 6-OH-BDE-47 stimulate aromatase activity. The aromatase inhibitor CGS
      16949A abolished this stimulatory activity and reduced estradiol levels in the
      control and treatment groups.

PMID- 23146759
TI  - Inhalation of chlorine causes long-standing lung inflammation and airway
      hyperresponsiveness in a murine model of chemical-induced lung injury.
AB  - Chlorine is highly irritating when inhaled, and is a common toxic industrial gas
      causing tissue damage in the airways followed by an acute inflammatory response.
      In this study, we investigated mechanisms by which chlorine exposure may cause
      reactive airways dysfunction syndrome (RADS) and we examined the dose-dependency
      of the development of symptoms. Mice were exposed to 50 or 200 ppm Cl(2) during a
      single 15 min exposure in a nose-only container. The experiment terminated 2, 6,
      12, 24, 48, 72 h and 7, 14, 28 and 90 days post exposure. Inflammatory cell
      counts in bronchoalveolar lavage (BAL), secretion of inflammatory mediators in
      BAL, occurrence of lung edema and histopathological changes in lung tissue was
      analyzed at each time-point. Airway hyperresponsiveness (AHR) was studied after
      24 and 48 h and 7, 14, 28 and 90 days. The results showed a marked acute response
      at 6h (50 ppm) and 12h (200 ppm) post exposure as indicated by induced lung
      edema, increased airway reactivity in both central and peripheral airways, and an
      airway inflammation dominated by macrophages and neutrophils. The inflammatory
      response declined rapidly in airways, being normalized after 48 h, but
      inflammatory cells were sustained in lung tissue for at least seven days. In
      addition, a sustained AHR was observed for at least 28 days. In summary, this
      mouse model of chlorine exposure shows delayed symptoms of hyperreactive airways
      similar to human RADS. We conclude that the model can be used for studies aimed
      at improved understanding of adverse long-term responses following inhalation of
      chlorine.

PMID- 23146760
TI  - Resveratrol inhibits TGF-beta1-induced epithelial-to-mesenchymal transition and
      suppresses lung cancer invasion and metastasis.
AB  - Epithelial-to-mesenchymal transition (EMT) is a cellular process during which
      epithelial polarized cells become motile mesenchymal-appearing cells, which in
      turn promotes carcinoma invasion and metastasis. Resveratrol (trans-3,4',5
      trihydroxystilbene) is a natural polyphenolic compound found in grapes, red wine
      and several other plants. Numerous reports in the literature indicate that
      resveratrol can suppress cancer invasion and metastasis. However, the underlying
      mechanisms of inhibiting metastasis by resveratrol are complex, not fully
      elucidated and the subject of intense scientific debate. Despite evidence
      indicating that EMT can be a target for resveratrol, little is known about the
      effect of resveratrol on lung cancer cells. Our previous studies demonstrated
      that TGF-beta1 induces EMT to promote lung adenocarcinoma invasion and
      metastasis. To understand the repressive role of resveratrol in lung cancer
      invasion and metastasis, we sought to investigate the potential use of
      resveratrol as an inhibitor of TGF-beta1-induced EMT development in A549 lung
      cancer cells in vitro. Here we show that when A549 cells are treated with TGF
      beta1 and resveratrol, the latter inhibits the initiation of TGF-beta1-induced
      EMT. Our results show that 20 MUM resveratrol increases expression of the
      epithelial phenotype marker E-cadherin and represses the expression of the
      mesenchymal phenotype markers, Fibronectin and Vimentin during the initiation of
      TGF-beta1-induced EMT. Resveratrol also inhibits expression of EMT-inducing
      transcription factors Snail1 and Slug, although the expression of the Twist1
      transcription factor remained unchanged. Resveratrol inhibits the TGF-beta1
      induced increase in cell adhesion, migration and invasion of A549 lung cancer
      cells. Taken together, our findings provide new evidence that resveratrol
      suppresses lung cancer invasion and metastasis in vitro through inhibiting TGF
      beta1-induced EMT.

PMID- 23146761
TI  - Cholestatic effect of epigallocatechin gallate in rats is mediated via decreased
      expression of Mrp2.
AB  - Epigallocatechin gallate (EGCG) has been shown to be protective in various
      experimental models of liver injury, although opposite effects have also been
      reported. Since its effect on biliary physiology has not been thoroughly
      investigated, the present study evaluated effect of EGCG on bile flow and bile
      acid homeostasis in rats. Compared to controls, EGCG treatment decreased bile
      flow by 23%. Hepatic paracellular permeability and biliary bile acid excretion
      were not altered by EGCG administration, but biliary glutathione excretion was
      reduced by 70%. Accordingly, the main glutathione transporter on the hepatocyte
      canalicular membrane, multidrug resistance-associated protein 2 (Mrp2), was
      significantly decreased at the protein level. EGCG administration also doubled
      plasma bile acid levels compared to controls. While protein levels of the main
      hepatic bile acid transporters were unchanged, the rate-limiting enzyme in the
      bile acid synthesis, Cyp7a1, was significantly increased by EGCG. Enhanced bile
      acid synthesis in these animals was also confirmed by a 2-fold increase in plasma
      marker 7alpha-hydroxy-4-cholesten-3-one. In contrast, EGCG markedly downregulated
      major bile acid transporters (Asbt and Ostalpha) and regulatory molecules (Shp
      and Fgf15) in the ileum. When EGCG was coadministered with ethinylestradiol, a
      potent cholestatic agent, it did not show any additional effect on the induced
      cholestasis. This study shows ability of EGCG to raise plasma bile acid
      concentrations, mainly through Cyp7a1 upregulation, and to decrease bile
      production through reduction in Mrp2-mediated bile acid-independent bile flow. In
      conclusion, our data demonstrate that under certain conditions EGCG may induce
      cholestasis.

PMID- 23146762
TI  - Gene expression profiling to identify potentially relevant disease outcomes and
      support human health risk assessment for carbon black nanoparticle exposure.
AB  - New approaches are urgently needed to evaluate potential hazards posed by
      exposure to nanomaterials. Gene expression profiling provides information on
      potential modes of action and human relevance, and tools have recently become
      available for pathway-based quantitative risk assessment. The objective of this
      study was to use toxicogenomics in the context of human health risk assessment.
      We explore the utility of toxicogenomics in risk assessment, using published gene
      expression data from C57BL/6 mice exposed to 18, 54 and 162 MUg Printex 90 carbon
      black nanoparticles (CBNP). Analysis of CBNP-perturbed pathways, networks and
      transcription factors revealed concomitant changes in predicted phenotypes (e.g.,
      pulmonary inflammation and genotoxicity), that correlated with dose and time.
      Benchmark doses (BMDs) for apical endpoints were comparable to minimum BMDs for
      relevant pathway-specific expression changes. Comparison to inflammatory lung
      disease models (i.e., allergic airway inflammation, bacterial infection and
      tissue injury and fibrosis) and human disease profiles revealed that induced gene
      expression changes in Printex 90 exposed mice were similar to those typical for
      pulmonary injury and fibrosis. Very similar fibrotic pathways were perturbed in
      CBNP-exposed mice and human fibrosis disease models. Our synthesis demonstrates
      how toxicogenomic profiles may be used in human health risk assessment of
      nanoparticles and constitutes an important step forward in the ultimate
      recognition of toxicogenomic endpoints in human health risk. As our knowledge of
      molecular pathways, dose-response characteristics and relevance to human disease
      continues to grow, we anticipate that toxicogenomics will become increasingly
      useful in assessing chemical toxicities and in human health risk assessment.

PMID- 23146763
TI  - A four-step approach to evaluate mixtures for consistency with dose addition.
AB  - Mixture risk assessment is often hampered by the lack of dose-response
      information on the mixture being assessed, forcing reliance on component formulas
      such as dose addition. We present a four-step approach for evaluating chemical
      mixture data for consistency with dose addition for use in supporting a component
      based mixture risk assessment. Following the concepts in the U.S. EPA mixture
      risk guidance (U.S. EPA, 2000a,b), toxicological interaction for a defined
      mixture (all components known) is departure from a clearly articulated definition
      of component additivity. For the common approach of dose additivity, the EPA
      guidance identifies three desirable characteristics, foremost of which is that
      the component chemicals are toxicologically similar. The other two
      characteristics are empirical: the mixture components have toxic potencies that
      are fixed proportions of each other (throughout the dose range of interest), and
      the mixture dose term in the dose additive prediction formula, which we call the
      combined prediction model (CPM), can be represented by a linear combination of
      the component doses. A consequent property of the proportional toxic potencies is
      that the component chemicals must share a common dose-response model, where only
      the dose coefficients depend on the chemical components. A further consequence is
      that the mixture data must be described by the same mathematical function
      ("mixture model") as the components, but with a distinct coefficient for the
      total mixture dose. The mixture response is predicted from the component dose
      response curves by using the dose additive CPM and the prediction is then
      compared with the observed mixture results. The four steps are to evaluate: (1)
      toxic proportionality by determining how well the CPM matches the single chemical
      models regarding mean and variance; (2) fit of the mixture model to the mixture
      data; (3) agreement between the mixture data and the CPM prediction; and (4)
      consistency between the CPM and the mixture model. Because there are four
      evaluations instead of one, some involving many parameters or dose groups, there
      are more opportunities to reject statistical hypotheses about dose addition, thus
      statistical adjustment for multiple comparisons is necessary. These four steps
      contribute different pieces of information about the consistency of the component
      and mixture data with the two empirical characteristics of dose additivity. We
      examine this four-step approach in how it can show empirical support for dose
      addition as a predictor for an untested mixture in a screening level risk
      assessment. The decision whether to apply dose addition should be based on all
      four of those evidentiary pieces as well as toxicological understanding of these
      chemicals and should include interpretations of the numerical and toxicological
      issues that arise during the evaluation. This approach is demonstrated with
      neurotoxicity data on carbamate mixtures. 

PMID- 23146764
TI  - In vitro approach to predict post-translational phosphorylation response to
      mixtures.
AB  - While exposure to chemical mixtures is an everyday reality, an understanding of
      their combined effects, and any potential prediction thereof, is extremely
      limited. Realistic exposures potentially consist of hundreds to thousands of
      chemicals per day, but even relatively simple binary mixture interactions can be
      inherently difficult to predict based upon the lack of temporal and spatial
      mechanisms for the individual constituents. To this end, we explore the concept
      of capitalizing on downstream convergence of intracellular signal transduction to
      experimentally simplify the means of determining xenobiotics that, when combined,
      could result in increased or unexpected toxicity. In a proof of principle study,
      we exposed HepG2 cells to deguelin, a natural isoflavonoid, alone and in
      combination with KCN, and determined the relative post-translational
      phosphorylation responses to several key proteins related to mitochondrial outer
      membrane permeabilization. Dose-dependent phosphorylation activity provides a
      clear identification of threshold response to low-level exposures, and crosstalk
      amongst selected proteins correctly forecasts mixtures interactions that may lead
      to increased toxicity. We then used Bliss Independence to determine if the
      experimentally measured mixture phosphorylation responses could be predicted with
      individual responses. Independence accurately predicted mixture interactions for
      deguelin and KCN (87.5%). To more fully exhaust independence as a model for
      determining potential pharmacodynamic interactions, we exposed HepG2 cells to
      deguelin and staurosporine, a broad kinase inhibitor; independence accurately
      predicted these mixture responses (77.5%). In this study, we demonstrate the
      potential of a new in vitro approach for the prediction of toxic mixtures
      interactions that is fundamentally driven by the interdependence of signal
      transduction and apoptosis. 

PMID- 23146765
TI  - 1H NMR-based metabonomics approach in a rat model of acute liver injury and
      regeneration induced by CCl4 administration.
AB  - The administration of carbon tetrachloride (CCl(4)) has been established as a
      model of toxin-induced acute and chronic liver injury. In the present study, we
      investigate the progression of the biochemical response to acute CCl(4)-induced
      liver injury, capturing metabolic variations during both toxic insult and
      regeneration using NMR-based metabonomic analysis of liver tissue and plasma. A
      single dose of CCl(4) (1 mL/kg BW) was intraperitoneally administered to male
      Wister rats sacrificed every 12h up to 72 h post treatment, while healthy animals
      served as controls. Acquired (1)H NMR spectra of liver tissue extracts and plasma
      samples were explored with multivariate analysis and the resulted models were
      correlated with conventional biochemical and histopathological indices of
      toxicity for monitoring the progression of experimental injury. The metabonomic
      analysis resulted in discrimination between the subjects under toxic insult (up
      to 36 h) and those at the regenerative phase (peaked at 48 h). At 72 h
      normalization of liver's pathology similar to the controls group was apparent.
      Principal component analysis (PCA) trajectories highlighted the time points of
      the greater degree of toxic insult and the regenerative state. A number of
      metabolites such as glucose, lactate, choline, formate exhibited variations
      suggesting CCl(4) induced impairment in essential biochemical pathways as energy
      metabolism, lipid biosynthesis and transmethylation reactions. The latter
      provides new evidence of B12 and folate pathways deficiency, indicative of new
      mechanistic implications possibly by direct inhibition of B12 dependent enzymes
      by the chlorinated radicals of CCl(4) metabolism.

PMID- 23146766
TI  - Physiologically based toxicokinetics of serum aflatoxin B1-lysine adduct in F344
      rats.
AB  - Aflatoxin B(1)-lysine adduct (AFB-Lys) is a reliable biomarker for aflatoxin
      exposure; however, a systematic toxicokinetic evaluation has not been reported.
      In this study, male F344 rats were orally exposed to single, or repeated, doses
      of AFB(1) and the toxicokinetics of serum AFB-Lys that followed treatments were
      investigated. A single-dose of AFB(1) increased serum AFB-Lys levels rapidly
      peaking at 4h, followed by first-order elimination, through which the half-life
      was estimated to be 2.31 days. A physiologically based pharmacokinetic model
      showed that approximately 3.00-3.90% and 1.12-1.98% of the administered AFB(1)
      doses were converted to serum AFB-Lys adducts at 2h and 24h post treatment,
      respectively. Repeated AFB(1) exposure at 5-25 MUg/kg body weight linearly
      increased serum AFB-Lys levels for 5 weeks in animals, resulting in a 1-1.5 times
      higher AFB-Lys level overall. This indicates the potential of this adduct as a
      reliable biomarker for repeated low dose exposure. Higher dose exposure at 75
      MUg/kg increased the level of AFB-Lys to a maximum at 2 weeks, followed by a
      gradual decrease to near plateau level up to 5 weeks. In conclusion, this study
      systematically evaluated the toxicokinetics of serum AFB-Lys adduct in F344 rats
      using a physiologically based pharmacokinetic model and robust statistical
      modeling analysis and provided a firm and clear understanding of the
      toxicokinetics of this biomarker.

PMID- 23146767
TI  - Immune modulatory and antioxidant effects of melatonin in experimental
      periodontitis in rats.
AB  - Melatonin is an important antioxidant, and through its anti-inflammatory effects
      it can control immune responses, oxidative stress, and defense cell infiltration.
      Periodontitis is a disease of the oral cavity and the generation of free radicals
      is an important consideration in this disease. Therefore, we examined the immune
      modulatory and antioxidant roles of melatonin in the treatment of periodontitis.
      In all, 30 male Wistar rats were randomly divided into three groups: the control
      group, the periodontitis-induced (PED) group, and the periodontitis+melatonin
      treatment (MEL+PED) group. The control group received no treatment, whereas
      periodontitis was induced in both the PED and the MEL+PED groups, with the
      MEL+PED group being treated with systemic melatonin. For the periodontitis
      induced groups, the rats' mandibular first molar teeth were ligatured (3-0
      cotton) in a submarginal position for 4 weeks, and then the ligature was removed.
      After removal of the ligature, melatonin was administered only to the MEL+PED
      group (an ip dose of 10mg/kg body wt for 15 days at 11:00 PM each day). In the
      histological examination, the MEL+PED group, which received the melatonin, showed
      reduced inflammatory cytokines (IL-1beta, from 97.47 to 84.24pg/ml; TNF-alpha,
      from 0.22530 to 0.22519pg/ml), regulated oxidative stress parameters (MDA, from
      41,458 to 30,708nmol/g; GSH, from 18,166 to 25,858nmol/mg), and less periodontal
      tissue destruction (CEJ-PL, lingual, from 244.54 to 140.57MUm; buccal, from 235.6
      to 158.93MUm; and CEJ-BC, lingual, from 383.65 to 287.76MUm; buccal, from 391.92
      to 296.12MUm). From these findings we conclude that, even when periodontitis was
      induced, melatonin reduced the oxidative damage in the rats' periodontal tissue
      by inhibiting the inflammatory effects and by restoring the antioxidants.

PMID- 23146769
TI  - Postprandial hyperglycemia on vascular endothelial function: mechanisms and
      consequences.
AB  - Vascular endothelial dysfunction precedes atherosclerosis and contributes to
      cardiovascular disease (CVD), which accounts for one-third of all deaths in the
      United States. Chronic hyperglycemia, such as that associated with diabetes, is
      well known to impair vascular function. However, recent evidence demonstrates
      that acute or postprandial hyperglycemia (PPH) not only exacerbates vascular
      endothelial dysfunction in individuals with chronic hyperglycemia but also
      transiently impairs vascular function in healthy individuals. Postprandial
      hyperglycemia has been shown to better predict future CVD mortality compared with
      fasting glucose in both diabetic and normoglycemic individuals. Compelling
      evidence exists suggesting that PPH-mediated insults to the vascular endothelium
      contribute to CVD, especially in pathophysiologic conditions whereby vascular
      recovery is compromised. Although the mechanisms by which PPH induces vascular
      dysfunction is not fully understood, oxidative stress-mediated disruptions in
      nitric oxide homeostasis are implicated as key events leading to vascular
      dysfunction associated with PPH. This review aims to highlight the findings of
      clinical studies using functional indices of vascular function to demonstrate
      that PPH impairs vascular function. We will also discuss the evidence showing the
      central involvement of oxidative stress in dysregulating nitric oxide homeostasis
      and contributing to PPH-mediated vascular endothelial dysfunction. Lastly, this
      review will identify areas of knowledge that remain limited and will provide
      recommendations for future investigation to more fully define PPH as an important
      risk factor for CVD.

PMID- 23146770
TI  - The degree of misreporting of the energy-adjusted intake of protein, potassium,
      and sodium does not differ among under-, acceptable, and over-reporters of energy
      intake.
AB  - It is unclear whether misreporting of nutrient intakes differs according to
      energy reporting status. We examined misreporting of dietary protein, potassium,
      and sodium in under-, acceptable, and over-reporters of energy intake. Our
      hypothesis was that degree of misreporting of these three nutrients differs among
      under-, acceptable, and over-reporters. Participants were 1043 Japanese women
      aged 18 to 22 years. Self-reported dietary intake was obtained using a diet
      history questionnaire. Under-, acceptable, and over-reporters of energy intake
      were identified based on the ratio of self-reported energy intake to estimated
      energy requirement (<0.70 [17.2%], 0.70-1.30 [78.1%], and >1.30 [4.7%],
      respectively). Misreporting of dietary protein, potassium, and sodium was
      assessed against the corresponding biomarker-based estimate derived from 24-hour
      urinary excretion. On average, the degree of misreporting of intake of energy and
      the three nutrients varied considerably. Absolute intake (amount per day) of the
      three nutrients was under-reported in under-reporters of energy intake and over
      reported in over-reporters compared with acceptable reporters. However, mainly
      because of high correlations between the ratio of self-reported energy intake to
      estimated energy requirement and the ratio of self-reported to biomarker-based
      estimates of absolute intake of three nutrients (Pearson correlation coefficient:
      0.64 for protein, 0.51 for potassium, and 0.37 for sodium), the degree of
      misreporting of the energy-adjusted intake of these nutrients based on the
      density method did not differ across categories of energy reporting status. In
      conclusion, these findings may lend support to the usefulness of adjustment for
      energy misreporting and the futility of merely excluding energy misreporters from
      analysis.

PMID- 23146768
TI  - Aging and reprogramming: a two-way street.
AB  - Aging is accompanied by the functional decline of cells, tissues, and organs, as
      well as a striking increase in a wide range of diseases. The reprogramming of
      somatic cells to induced pluripotent stem cells (iPSCs) opens new avenues for the
      aging field and has important applications for therapeutic treatments of age
      related diseases. Here we review emerging studies on how aging and age-related
      pathways influence iPSC generation and property. We discuss the exciting
      possibility that reverting to a pluripotent stem cell stage erases several
      deficits associated with aging and offers new strategies for rejuvenation.
      Finally, we argue that reprogramming provides a unique opportunity to model aging
      and perhaps exceptional longevity.

PMID- 23146771
TI  - A significant correlation between the plasma levels of coenzyme Q10 and vitamin B
      6 and a reduced risk of coronary artery disease.
AB  - Coronary artery disease (CAD) is the leading cause of death worldwide. The
      purpose of this study was to investigate the relationship between plasma levels
      of coenzyme Q10 and vitamin B-6 and the risk of CAD. Patients with at least 50%
      stenosis of one major coronary artery identified by cardiac catheterization were
      assigned to the case group (n = 45). The control group (n = 89) comprised healthy
      individuals with normal blood biochemistry. The plasma concentrations of coenzyme
      Q10 and vitamin B-6 (pyridoxal 5'-phosphate) and the lipid profiles of the
      participants were measured. Subjects with CAD had significantly lower plasma
      levels of coenzyme Q10 and vitamin B-6 compared to the control group. The plasma
      coenzyme Q10 concentration (beta = 1.06, P = .02) and the ratio of coenzyme Q10
      to total cholesterol (beta = .28, P = .01) were positively correlated with
      vitamin B-6 status. Subjects with higher coenzyme Q10 concentration (>=516.0
      nmol/L) had a significantly lower risk of CAD, even after adjusting for the risk
      factors for CAD. Subjects with higher pyridoxal 5'-phosphate concentration
      (>=59.7 nmol/L) also had a significantly lower risk of CAD, but the relationship
      lost its statistical significance after adjusting for the risk factors of CAD.
      There was a significant correlation between the plasma levels of coenzyme Q10 and
      vitamin B-6 and a reduced risk of CAD. Further study is needed to examine the
      benefits of administering coenzyme Q10 in combination with vitamin B-6 to CAD
      patients, especially those with low coenzyme Q10 level.

PMID- 23146772
TI  - Factors across home, work, and school domains influence nutrition and physical
      activity behaviors of nontraditional college students.
AB  - Nontraditional college students (older, part-time, and/or working) have less
      healthful nutrition and physical activity behaviors compared to traditional
      students, yet few health promotion efforts focus on nontraditional students. The
      purpose of this study was to use qualitative methods to explore factors affecting
      nutrition and physical activity behaviors of nontraditional students. Fourteen
      semi-structured individual interviews were conducted with nontraditional
      undergraduate students attending a large university. The sample had a median age
      of 25 (range, 21-64), 57% were men, 43% were racial/ethnic minorities, and 57%
      were employed (mean 22 hours/week). Data were coded using a systematic team-based
      approach. Consistent themes (mentioned by 4+ students) were identified and
      categorized into three domains: home, work, and school. Home (themes:
      neighborhood characteristics, family, partners), work (theme: work environment),
      and school (themes: cafeteria, vending machines) factors consistently influenced
      positive nutrition behaviors. Similarly, home (themes: neighborhood including
      safety, friends from home, partner,), work (theme: work environment), and school
      (themes: not having a car, campus structure, campus gym, friends at school)
      factors consistently influenced positive physical activity. Financial resources
      and perceptions of autonomy had influence across domains. Results indicate
      consistent influences on nutrition and physical activity behaviors across home,
      work, and school domains for nontraditional college students. Study findings
      suggest possible, and sometimes unconventional, intervention strategies to
      promote healthful eating and physical activity. For example, when cafeteria meal
      plans are not offered and financial constraints limit eating at the cafeteria,
      encouraging healthful choices from vending machines could be preferable to not
      eating at all.

PMID- 23146773
TI  - Serum levels of zinc, calcium, and iron are associated with the risk of
      preeclampsia in pregnant women.
AB  - Evidence indicates that various elements, including antioxidant minerals, might
      play an important role in preeclampsia (PE). This study was carried out to
      investigate the relationship between serum mineral levelsof zinc, calcium, iron,
      and selenium and the risk of preeclampsia in Korean women. Twenty-nine normal
      controls and 30 women with preeclampsia were recruited for the study.
      Preeclampsia was defined as having high blood pressure (>= 140/90 mm Hg after 20
      weeks gestation) and proteinuria (>=300 mg/24 hours). Serum mineral content was
      determined by instrumental neutron activation analysis. Serum zinc (P < .0001)
      and calcium (P = .0188) levels were lower in women with preeclampsia than those
      of normal women, while serum iron was significantly higher in women with
      preeclampsia (P = .0045). The odds ratio for preeclampsia was lower in women with
      higher serum zinc levels than those with lower levels after adjustment for age,
      height, and weight before delivery (P < .0001). The adjusted odds ratio for
      preeclampsia also decreased across tertiles of serum calcium concentration (P =
      .0452). However, there was an increased adjusted odds ratio for preeclampsia
      across tertiles of serum iron level (P = .0104). These results suggest that
      levels of serum minerals such as zinc, calcium, and iron may be associated with
      the risk of preeclampsia in Korean pregnant women.

PMID- 23146774
TI  - Black soybean anthocyanins inhibit adipocyte differentiation in 3T3-L1 cells.
AB  - Anthocyanins are naturally occurring polyphenolic pigments in plants that have
      been shown to decrease weight gain and insulin resistance in mice-fed high-fat
      diets. We investigated the effects of anthocyanins on cell growth,
      differentiation, and lipolysis in 3T3-L1 cells to test our hypothesis that
      anthocyanins could reduce adipose tissue mass by acting directly on adipocytes.
      Anthocyanin extracts from black soybeans were used and composed of 3 of the
      following major anthocyanins: cyanidine-3-O-glucoside (68.3%), delphinidin-3-O
      glucoside (25.2%), and petunidin-3-O-glucoside (6.5%). Treatment with 12.5 and 50
      MUg/mL of black soybean anthocyanins exhibited inhibitory effects on the
      proliferation of both preconfluent preadipocytes (P < .01) and maturing
      postconfluent adipocytes (P < .01). In fully differentiated adipocytes, the
      number of viable cells was reduced by black soybean anthocyanins (P < .01).
      Treatment with 50 MUg/mL of black soybean anthocyanins slightly increased
      epinephrine-induced lipolysis but decreased the basal lipolysis of fully
      differentiated adipocytes (P < .05). Black soybean anthocyanins also reduced
      lipid accumulation and suppressed the expression of the peroxisome proliferator
      activated receptor gamma, a major transcription factor for the adipogenic gene (P
      < .01). These results suggest that black soybean anthocyanins inhibit adipocyte
      differentiation and basal lipolysis, which may contribute to their antiobesity
      and antidiabetic properties.

PMID- 23146775
TI  - Oleuropein reduces free fatty acid-induced lipogenesis via lowered extracellular
      signal-regulated kinase activation in hepatocytes.
AB  - Oleuropein, a bitter glucoside found in green olive leaves, and its metabolite
      hydroxytyrosol display powerful antioxidant activity both in vivo and in vitro.
      In this study, we hypothesized that the antioxidant activity of oleuropein could
      attenuate hepatic steatosis. To test this hypothesis, we established steatotic
      hepatocytes using HepG2 and FL83B cells treated with free fatty acids (FFAs)
      (oleate:palmitate, 2:1). To confirm hepatic steatosis, the intracellular lipid
      levels were quantitatively measured by Nile Red staining, and the sizes and
      distributions of lipid droplets were visualized by transmission electron
      microscopy. The expression of PAT family proteins as well as of adipose
      differentiation-related protein and tail interacting protein (TIP47) was
      evaluated by reverse transcriptase polymerase chain reaction and immunoblotting.
      To examine the cellular and molecular events associated with oleuropein, annexin
      V/propidium iodide staining and immunoblotting were performed. Oleuropein
      decreased the number and size of lipid droplets in FFA-treated cells and reduced
      intracellular triglyceride accumulation. However, it did not affect the
      expression of lipid droplets-associated PAT family proteins, including adipose
      differentiation-related protein and TIP47. In addition, oleuropein reduced FFA
      induced extracellular signal-regulated kinase activation but had no effect on c
      Jun N-terminal kinase or AKT activation. Given its protective effects against FFA
      induced hepatocellular steatosis, oleuropein may be a lipid-lowering agent.

PMID- 23146776
TI  - Chronic administration of dietary grape seed extract increases colonic expression
      of gut tight junction protein occludin and reduces fecal calprotectin: a
      secondary analysis of healthy Wistar Furth rats.
AB  - Animal studies have demonstrated the potential of grape seed extract (GSE) to
      prevent metabolic syndrome, obesity, and type 2 diabetes. Recently, metabolic
      endotoxemia induced by bacterial endotoxins produced in the colon has emerged as
      a possible factor in the etiology of metabolic syndrome. Improving colonic
      barrier function may control endotoxemia by reducing endotoxin uptake. However,
      the impact of GSE on colonic barrier integrity and endotoxin uptake has not been
      evaluated. We performed a secondary analysis of samples collected from a chronic
      GSE feeding study with pharmacokinetic end points to examine potential modulation
      of biomarkers of colonic integrity and endotoxin uptake. We hypothesized that a
      secondary analysis would indicate that chronic GSE administration increases
      colonic expression of intestinal tight junction proteins and reduces circulating
      endotoxin levels, even in the absence of an obesity-promoting stimulus. Wistar
      Furth rats were administered drinking water containing 0.1% GSE for 21 days.
      Grape seed extract significantly increased the expression of gut junction protein
      occludin in the proximal colon and reduced fecal levels of the neutrophil protein
      calprotectin, compared with control. Grape seed extract did not significantly
      reduce serum or fecal endotoxin levels compared with control, although the
      variability in serum levels was widely increased by GSE. These data suggest that
      the improvement of gut barrier integrity and potential modulation of endotoxemia
      warrant investigation as a possible mechanism by which GSE prevents metabolic
      syndrome and associated diseases. Further investigation of this mechanism in high
      fat feeding metabolic syndrome and obesity models is therefore justified.

PMID- 23146777
TI  - Curcumin ingestion and exercise training improve vascular endothelial function in
      postmenopausal women.
AB  - Vascular endothelial function is declines with aging and is associated with an
      increased risk of cardiovascular disease. Lifestyle modification, particularly
      aerobic exercise and dietary adjustment, has a favorable effect on vascular
      aging. Curcumin is a major component of turmeric with known anti-inflammatory and
      anti-oxidative effects. We investigated the effects of curcumin ingestion and
      aerobic exercise training on flow-mediated dilation as an indicator endothelial
      function in postmenopausal women. A total of 32 postmenopausal women were
      assigned to 3 groups: control, exercise, and curcumin groups. The curcumin group
      ingested curcumin orally for 8 weeks. The exercise group underwent moderate
      aerobic exercise training for 8 weeks. Before and after each intervention, flow
      mediated dilation was measured. No difference in baseline flow-mediated dilation
      or other key dependent variables were detected among the groups. Flow-mediated
      dilation increased significantly and equally in the curcumin and exercise groups,
      whereas no changes were observed in the control group. Our results indicated that
      curcumin ingestion and aerobic exercise training can increase flow-mediated
      dilation in postmenopausal women, suggesting that both can potentially improve
      the age-related decline in endothelial function.

PMID- 23146778
TI  - Occult hepatitis B virus and the risk for chronic liver disease: a meta-analysis.
AB  - BACKGROUND: The role of occult hepatitis B virus infection as a cause of liver
      disease is still debated although many studies found a higher prevalence of this
      condition in subjects than those without liver disease compared. A recent meta
      analysis showed an increased risk of hepatocellular carcinoma for occult
      hepatitis B virus infection. AIMS: We carried out a meta-analysis of
      observational studies to summarize the existing evidence and assess
      quantitatively the association between occult hepatitis B virus infection and
      chronic liver disease. METHODS: We searched the available literature on this
      issue published up to May 2012 using PubMed and EMBASE. All articles that
      provided enough information to estimate the chronic liver disease risk associated
      with occult hepatitis B virus infection were selected. Fourteen studies were
      retrieved. RESULTS: A total of 1503 subjects with (cases) and 2052 without
      chronic liver disease (controls) were included. The summary odds ratio for
      chronic liver disease from all studies was 8.9 (95% confidence interval: 4.1
      19.5). The meta-analysis restricted to 7 studies with more precise effect
      estimate (wt%>8%) provided a lower odds ratio estimate (odds ratio=3.9; 95%
      confidence interval: 1.7-9.0). CONCLUSIONS: These findings suggest a relevant
      association between occult hepatitis B virus infection and chronic liver disease,
      confirming the hypothesis that hepatitis B virus may play a pathogenic role even
      in the "occult" status.

PMID- 23146779
TI  - Lateralized implicit sequence learning in uni- and bi-manual conditions.
AB  - It has been proposed that the right hemisphere (RH) is better suited to acquire
      novel material whereas the left hemisphere (LH) is more able to process well
      routinized information. Here, we ask whether this potential dissociation also
      manifests itself in an implicit learning task. Using a lateralized version of the
      serial reaction time task (SRT), we tested whether participants trained in a
      divided visual field condition primarily stimulating the RH would learn the
      implicit regularities embedded in sequential material faster than participants in
      a condition favoring LH processing. In the first study, half of participants were
      presented sequences in the left (vs. right) visual field, and had to respond
      using their ipsilateral hand (unimanual condition), hence making visuo-motor
      processing possible within the same hemisphere. Results showed successful
      implicit sequence learning, as indicated by increased reaction time for a
      transfer sequence in both hemispheric conditions and lack of conscious knowledge
      in a generation task. There was, however, no evidence of interhemispheric
      differences. In the second study, we hypothesized that a bimanual response
      version of the lateralized SRT, which requires interhemispheric communication and
      increases computational and cognitive processing loads, would favor RH-dependent
      visuospatial/attentional processes. In this bimanual condition, our results
      revealed a much higher transfer effect in the RH than in the LH condition,
      suggesting higher RH sensitivity to the processing of novel sequential material.
      This LH/RH difference was interpreted within the framework of the Novelty
      Routinization model [Goldberg, E., & Costa, L. D. (1981). Hemisphere differences
      in the acquisition and use of descriptive systems. Brain and Language, 14(1), 144
      173] and interhemispheric interactions in attentional processing [Banich, M. T.
      (1998). The missing link: the role of interhemispheric interaction in attentional
      processing. Brain and Cognition, 36(2), 128-157].

PMID- 23146780
TI  - Decline in executive control during acute bouts of exercise as a function of
      exercise intensity and fitness level.
AB  - Studies on the effects of acute bouts of cardiovascular exercise on cognitive
      performances show contradictory findings due to methodological differences (e.g.,
      exercise intensity, cognitive function assessed, participants' aerobic fitness
      level, etc.). The present study assessed the acute effect of exercise intensity
      on cognition while controlling for key methodological confounds. Thirty-seven
      participants (M(age)=23. 8 years; SD=2.6) completed a computerized modified
      Stroop task (involving denomination, inhibition and switching conditions) while
      pedalling at 40%, 60% and 80% of their peak power output (PPO). Results showed
      that in the switching condition of the task, error rates increased as a function
      of exercise intensity (from 60% to 80% of PPO) in all participants and that lower
      fit individuals showed increased reaction time variability. This suggests that
      acute bouts of cardiovascular exercise can momentarily alter executive control
      and increase performance instability in lower fit individuals.

PMID- 23146781
TI  - [The role of adult bone marrow derived mesenchymal stem cells in the repair of
      tissue injuries].
AB  - Mesenchymal stem cells, which reside in adult bone marrow are multipotent, have
      an excellent regeneration potential for tissue repair. These cells are able to
      differentiate in cell culture not only into mesodermal lineages but also into
      other lineages of ectodermal and endodermal cells. This regenerative process is
      assisted by application of bioactive molecules, specific growth factors and
      biomaterials (scaffolds). The cell therapy is successfully used in the treatment
      of bone defects, nonunions, osteoblasts formed from the mesenchymal stem cells.
      At present, there are encouraging data in the clinical practice. The mesenchymal
      stem cell seems to be successful in the regeneration of articular cartilage.
      There are further promising data for the application of mesenchymal stem cells in
      the treatment of myocardial infarction, neurologic diseases, liver and kidney
      diseases and injuries and diabetes mellitus. The aim of this review is to survey
      the molecular characteristics of mesenchymal stem cells and specific growth
      factors using the data of preclinical investigations and to call attention to
      their possible clinical application.

PMID- 23146782
TI  - [Autologous fat transplantation in the modern reconstructive surgery of breast
      cancer].
AB  - Autologous fat transplantation is often used in aesthetic plastic surgery, and is
      recently becoming increasingly popular in the reconstruction of soft tissue
      defects following oncological surgery. A still not standardized technique of fat
      transplantation for breast cancer reconstruction is rapidly getting popular. The
      procedure is not a passive volume replacement, but transplantation of
      biologically active tissue bearing endocrine, paracrine, exocrine functions and
      containing fat-derived stem cells, which in the tumorous environment raises many
      questions in relation to the oncological safety and diagnostic follow-up.
      Although long-term results based on prospective, randomized studies are not yet
      available, published clinical experience is promising and reveals an effective
      and surgically safe procedure if used with appropriate indications and
      techniques. The authors conducted a broad review of the literature, presenting
      indications, technique, molecular interactions, and potential risks of the
      clinical results of autologous fat transplantation in the breast cancer
      reconstructive surgery. The authors initiated that breast and plastic surgeons
      should promote adequate long term follow-up of breast cancer patients who
      underwent breast reconstruction with autologous fat transplantation by the
      establishment of national registries.

PMID- 23146784
TI  - [The case of the Raving Reporter with the Blazek twins].

PMID- 23146783
TI  - [Obstetrical and gynecological relevance of inflammatory bowel disease].
AB  - INTRODUCTION: Inflammatory bowel disease may show a life long persistence, while
      female fertility is time-limited. AIM: The aim of the authors was to obtain more
      knowledge about the obstetrical-gynecological aspects of this disorder. METHODS:
      The authors evaluated 100 patients with inflammatory bowel disease and 100
      healthy women with a self-composed questionnaire. RESULTS: Menarche occurred
      significantly earlier in patients than in controls (p = 0,03). Either the
      activity of the disease, or the therapy itself may initiate irregularities in the
      menstrual cycle. Patients used contraceptives less frequently than controls (p =
      0,002), and the time from family-planning to conception was longer in patients.
      Symptoms of bowel disease during pregnancy were not as severe as before and after
      pregnancy (p<0,001). Excess weight had a beneficial effect on symptoms during
      pregnancy (p = 0,042) and on the frequency of complications. Preterm birth and
      low birth weight were more frequent in newborns of patients (p = 0,019).
      CONCLUSION: Pregnancy has positive effect on the symptoms of inflammatory bowel
      disease in case gestation occurs in a stable period of the inflammatory bowel
      disease.

PMID- 23146786
TI  - [Evaluation of CD4+CD161+CD196+ and CD4+IL-17+ Th17 cells in the peripheral blood
      of young patients with Hashimoto's thyroiditis and Graves' disease].
AB  - INTRODUCTION: Up till now, altered balance of Th1 and Th2 immune cells has been
      postulated to play an important role in the pathogenesis of autoimmune thyroid
      diseases (AITD). However, recent studies on thyroid diseases suggest a new role
      for Th17 (T helper 17) cells that have been classified as a new lineage, distinct
      from Th1, Th2 and Treg cells. Despite wide interest, the role of Th17 cells in
      the pathogenesis of inflammatory and autoimmune diseases is still being debated.
      Th17 cells are involved in immune responses against extracellular pathogens and
      have the ability to secrete cytokines: IL-17, IL-17F, IL-22 and IL-21. Th17 cells
      can be characterized by several surface markers, i.e. CCR6 (CD196), IL-23R, IL
      12Rbeta2 and CD161. AIM OF THE STUDY: Was to estimate the frequencies of
      circulating CD4+CD161+CD196+ and CD4+IL-17+ Th17 cells in patients with Graves'
      disease (GD, n=20, mean age +/- SEM 14.9 +/- 6 years), Hashimoto's thyroiditis
      (HT, n=20, mean age +/- SEM 15.2+/-3 yrs) and in healthy controls (C, n=20, mean
      age +/- SEM 15.4 +/- 2 yrs). MATERIAL AND METHODS: Polychromatic flow cytometry
      and several fluorochrome-conjugated monoclonal antibodies were applied to
      delineate Th17 cells with either CD4+CD161+CD196+ or CD4+IL-17+ phenotype using
      apparatus FACSCalibur (BD Biosciences). Thyroid anti-TSH receptor immunoglobulins
      (TRAK), anti-thyroperoxidase (anti-TPO) and anti-thyroglobulin (anti-TG)
      antibodies were measured in all the samples using electrochemiluminescence
      "ECLIA" with Modular Analytics E170 analyzer (Roche Diagnostics, Poland).
      RESULTS: In untreated HT children we observed an increased percentage of
      CD4+CD161+CD196+ (7.1 +/- 3.5 vs. 3.7 +/- 1.8; p <0.04) and CD4+IL-17+ (3.7 +/-
      2.7 vs. 1.4+/-0.4; p <0.01) Th17 lymphocytes in comparison to the healthy
      controls. In untreated and treated GD children we did not reveal such
      abnormalities in the population of these cells compared to the controls. In cases
      with HT, a positive correlation between the percentage of CD4+IL-17+ and
      CD4+CD161+CD196+ T cells and serum level of anti-TPO antibodies (r=0.48; p
      <0.025; r=0.65; p <0.01; respectively) was detected. CONCLUSIONS: We conclude
      that the increased percentage of Th17 cells in children with untreated
      Hashimoto's thyroiditis can suggest their role in initiation and development of
      immune and inflammatory processes in this endocrinopathy.

PMID- 23146787
TI  - Behavioral and intellectual functioning in patients with tyrosinemia type I.
AB  - INTRODUCTION: In tyrosinemia type I (TT1) increased level of tyrosine and
      phenylalanine (both precursors of neurotransmitters), may potentially influence
      patients' cognitive development. AIM OF THE STUDY: Was to evaluate if the
      children during the treatment with phenylalanine- and tyrosine-restricted diet
      and nitisinone present with cognitive, emotional or behavioral problems and to
      find out whether plasma tyrosine and phenylalanine levels may have impact on
      this. MATERIAL AND METHODS: Cognitive development and behavior, together with
      plasma tyrosine and phenylalanine levels, were analyzed in eight patients during
      their first five years of nitisinone treatment. Psychological examination has
      been done using standard diagnostic methods: the Wechsler Intelligence Scale for
      Children (WISC-R) and Child Behavior Checklist CBCL/4-18 (parents version).
      RESULTS: The results showed that in the patients with TT1, attention deficit is
      not rare, and may be connected with the variation of the plasma tyrosine level.
      Moreover the reverse correlation between attention deficit and results from
      verbal scale may suggest decreased ability to verbal reasoning, comprehension,
      verbal expression and school difficulties. CONCLUSIONS: What is significant for
      the presence of attention disorders and the related difficulties in using the
      intellectual potential is not the level of tyrosine (high vs. low), but its
      changes (stability vs. instability). Therapeutic trials to stabilize the tyrosine
      level could alleviate the difficulties in focusing attention. Following a diet is
      necessary for keeping the normal level of tyrosine.

PMID- 23146788
TI  - [Metabolic acidosis in children with newly diagnosed type 1 diabetes and risk
      factors of urolithiasis].
AB  - INTRODUCTION: Urolithiasis is increasingly being diagnosed in children. Some of
      the major risk factors for kidney stones are hipercalciuria, hiperoxaluria,
      hipocitraturia and hydrogen ion content measured by pH. Recently, more and more
      attention is being paid to the impact of diabetes type 1 and 2 on the development
      of nephrolithiasis especially in periods of poor metabolic control. AIM OF THE
      STUDY: was to evaluate the BRI (bonn risk index - rate of spontaneous
      crystallization of calcium oxalate), the concentration of oxalate, citrate and
      urine pH in children with acid-base balance disturbances occurring in patients
      with newly diagnosed type 1 diabetes (DMT1). MATERIAL AND METHODS: The study
      group included 40 patients aged 6 to 17 years (average age +/- SD: 12,58 +/-
      3,33) with newly diagnosed DMT1. The study was performed twice: at the beginning
      of the disease, immediately after the treatment of diabetic ketoacidosis (study
      I) and after obtaining satisfactory metabolic control (study II), that is after
      about two weeks. The control group consisted of 100 children (6-17 years, average
      age 12,34 +/- 3,96) without symptoms suggestive of urolithiasis. In every child,
      a 24-hour urine sample was collected. BRI was implemented in the urine by his own
      semi-micro method. RESULTS: Ionized calcium level was significantly higher
      immediately after the diagnosis of type 1 diabetes compared to the control group
      (0,68+/-0,67 vs. 0,40 +/- 0,18 mmol/l; p<0,001) and to study II (0,68 +/- 0,67
      vs. 0,28 +/- 0,23 mmol/l; p=0,008). BRI value was significantly higher in early
      onset compared to the control group and the study II (3,18 +/- 5,54 vs. 0,66 +/-
      0,52, p<0,001; 3,18 +/- 5,54 vs. 0,64 +/- 1,56; p=0,034). BRI correlated
      inversely with pH at admission to the hospital (r=-0,53, p=0,0023). CONCLUSIONS:
      Metabolic alterations occurring during diabetic ketoacidosis at diagnosis of new
      type 1 diabetes may predispose to the development of the urinary stones, and
      thereby to the kidney damage.

PMID- 23146789
TI  - Analysis of selected anthropometric parameters of 6-year-old children in Warsaw
      compared to the peer population in the years 1996-1999.
AB  - INTRODUCTION: Beside the positive tendencies in somatic development seen in the
      population of children and adolescents in Poland (e.g. the trend of increasing
      body height that has continued over many years), certain unfavorable phenomena
      are also observed. In recent decades, disorders connected with a deficiency or
      excess of body mass - excessive adiposity in particular - have become important
      health and social problems. This poses a considerable threat for being
      overweight, for obesity, and for other diseases of civilization. AIM OF THE
      STUDY: The research targeted the evaluation of selected anthropometric
      parameters: height-weight indices, circumferences, and skinfold thicknesses in
      the population of 6-year-old children in Warsaw in comparison with their peer
      population in 1996-1999, as well as estimation of the frequency of abnormal
      percentile values of the aforementioned anthropometric parameters: values below
      the 10th percentile and above the 90th percentile. MATERIALS AND METHODS: The
      research included a sample of 160 randomly chosen children (81 boys and 79 girls)
      born in 2005 who attended public and private kindergartens in Warsaw. The average
      age of this group was 5.71 +/- 0.28 years. The study was carried out in the first
      quarter of 2011. The following somatic parameters were measured: body height,
      body mass, chest and arm circumference, triceps, and subscapular and abdominal
      skinfold thickness. The height-weight indices including Rohrer's Index and Body
      Mass Index (BMI) were calculated. Using a method of normalization of numerical
      data, the obtained measurements were compared to the measurements of the peer
      population (n=233) from 1996 to 1999, and the significance of differences between
      mean values in both groups was assessed with Student's t-tests. The percentage
      tables with the ranges of the below normative (<10th percentile) and above
      normative (>90th percentile) percentile values of the studied parameters and
      indices were prepared on the basis of the percentile charts that presented the
      anthropometric parameters of children in Warsaw 12-15 years prior to this
      research. RESULTS: Results especially worth underscoring are higher skinfold
      thickness values for children who took part in the research compared to the peer
      population examined in 1996-1999. This tendency was more typical of girls than
      boys and was observed mostly in subscapular skinfold thickness. Some of the
      differences between the studied population and the control group were
      statistically significant (girls: triceps skinfold thickness p <0.05, subscapular
      skinfold thickness p <0.01, sum of 3 skinfolds p <0.05; boys: subscapular
      skinfold thickness p <0.01). CONCLUSIONS: During the last 12-15 years, a certain
      tendency for greater body fatness in 6-year-old children in Warsaw has been
      noticed. In the present research, the alarming symptoms that indicate the threat
      for being overweight and for obesity were observed on the basis of measurement of
      skinfold thickness. However, these symptoms were not found in the case of the
      analysis of selected height-weight indices. The relatively high percentages of
      extreme values (values below the 10th percentile and above the 90th percentile)
      of the analyzed parameters suggest that there are many children with a non
      normative somatic build in the examined group.

PMID- 23146790
TI  - Chronic complications of diabetes mellitus related to the respiratory system.
AB  - The quality of life in patients with diabetes mellitus is mainly determined by
      chronic diabetic complications which may affect all organ tissues including
      respiratory system. Microangiopathy of pulmonary capillaries, autonomic
      neuropathy, myopathy of respiratory muscles or changes in collagen belong to
      supposed pathophysiological pathways. This paper brings brief review about
      reported functional consequences in subjects with diabetes - decreased vital lung
      capacity and pulmonary volumes, decreased diffuse lung capacity for carbon
      monoxide, lower basal bronchial tone, lower cough reflex sensitivity, increased
      incidence of sleep obstructive apnea, increase in respiratory infections,
      disorders in respiratory muscles or phrenical nerve. Examination of pulmonary
      functions may serve for early detection of chronic complications in patients with
      diabetes.

PMID- 23146791
TI  - Thyroid axis alterations in childhood obesity.
AB  - In recent years researchers have become increasingly interested in the particular
      relation between the function of the thyroid gland and the body mass in the
      population of obese children. Numerous studies have been conducted and the
      literature on the related issues has been abounding. Several thereof have strived
      at pinpointing a significant link between the function of the thyroid axis and
      the body mass. Yet, it still remains to be clarified whether these subtle changes
      in the level of thyroid hormones and TSH observed in childhood obesity are
      responsible for the increased body mass or rather they represent a secondary
      phenomenon. The mechanism most often put forward by the researchers that links
      obesity to thyroid function is the increased level of leptin, which affects
      neurones in the hypothalamus and the thyroid axis causing TRH and TSH secretion.
      The body mass is positively correlated with serum leptin and elevated level of
      leptin is connected with an increase in TSH level. However, there is still
      controversy whether these inconspicuous differences observed in thyroid axis
      merit the treatment with thyroxine since these changes seem to constitute a
      consequence rather than a cause of obesity. Therefore, as most authors postulate,
      primary importance should be placed on lifestyle changes and body weight
      reduction leaving substitutive treatment as a supplementary option. The purpose
      of this review is to present the most current issues on child obesity and the
      related malfunction of the thyroid axis through an overview of international
      publications from the years 1996-2011.

PMID- 23146792
TI  - Effect of cadmium chloride on secretion of 17beta-estradiol by the ovarian
      follicles of common carp, Cyprinus carpio.
AB  - Cadmium (Cd(2+)) is a common environmental pollutant present in wastes associated
      with mining, smelting and electroplating. It is a major constituent of the
      tobacco smoke. Exposure of this heavy metal has been linked to wide range of
      detrimental effects on mammalian reproduction particularly on ovarian
      steroidogenesis. Low doses of Cd(2+) are reported to stimulate ovarian luteal
      progesterone synthesis whereas high doses inhibited it. Cd(2+) exposure is also
      reported to inhibit gonadal function in fish. In the present study the effects of
      cadmium chloride (CdCl(2)) on the secretion of gonadotropin-induced 17beta
      estradiol was examined in female common carp Cyprinus carpio. Vitellogenic stage
      fish were exposed to physiological safe dose of CdCl(2) for 0, 24, 48 and 96 h
      and serum and ovarian 17beta-estradiol levels were estimated. In the in vitro
      experiments, vitellogenic follicles were incubated with CdCl(2) and a dose- and
      time-dependent effects on steroid production were estimated induced by LH.
      Exposure of fish with CdCl(2) gradually attenuated serum and ovarian 17beta
      estradiol levels with increasing time and maximum inhibition was noticed after 96
      h. Administration of CdCl(2) to the incubations significantly inhibited LH
      induced release of 17beta-estradiol in vitro. To clarify the mechanism of
      attenuated production of 17beta-estradiol, in vitro effects of CdCl(2) on LH
      induced P450 aromatase activity (conversion of testosterone to 17beta-estradiol)
      and cytochrome P450arom gene expression in carp ovarian follicles were evaluated.
      Results show that LH-stimulated P450 aromatase activity and P450arom gene
      expression in ovarian follicles were significantly inhibited by CdCl(2). The
      present study further demonstrated that LH-induced stimulation of ovarian
      steroidogenic factor-1 (SF-1) which activates aromatase enzyme, is strongly
      inhibited by cadmium chloride treatment.

PMID- 23146793
TI  - Seventh Congress of the Asia and Oceania Society for Comparative Endocrinology.

PMID- 23146794
TI  - Parental knowledge of guidelines for treatment of paediatric acute
      gastroenteritis.

PMID- 23146795
TI  - Antioxidant activity in HIV and malaria co-infected subjects in Anambra State,
      southeastern Nigeria.
AB  - OBJECTIVE: To determine the antioxidant status of HIV and malaria co-infected
      participants. METHODS: Blood samples collected from the 193 randomly recruited
      participants were used for HIV screening, Plasmodium falciparum antigen
      screening, malaria parasite density count, CD4(+) T cell count, glutathione
      reductase, glutathione peroxidase and total antioxidant status measurement.
      Standard laboratory methods were used for the analysis. RESULTS: The results
      showed that glutathione reductase, glutathione peroxidase, total antioxidant
      status and CD4(+) T cell count were significantly lowered in symptomatic HIV
      participants with and without malaria co-infection (P<0.01) in each case compared
      with control participants. Also, glutathione reductase, glutathione peroxidise,
      total antioxidant status and CD4(+) T cell count were significantly lowered in
      asymptomatic HIV participants with and without malaria co-infection (P<0.05) in
      each case, compared with control participants without malaria. Similarly, these
      antioxidants were significantly lowered in control participants with malaria
      infection (P<0.05) compared with control participants without malaria. The
      malaria parasite density in symptomatic HIV infected participants was negatively
      associated with glutathione reductase (r = -0.906, P<0.01), glutathione
      peroxidase (r = -0.719, P<0.01) and total antioxidant status (r = -0.824,
      P<0.01). CONCLUSIONS: The antioxidant activity was affected in HIV infected
      participants with malaria co-infection. Malaria co-infection in HIV seems to
      exert additional burden on antioxidants. This calls for concern in malaria
      endemic areas with increasing prevalence of HIV infection.

PMID- 23146796
TI  - Epidemiology and antibiotic resistance of bacterial meningitis in Dapaong,
      northern Togo.
AB  - OBJECTIVE: To assess the seasonality of the bacterial meningitis and the
      antibiotic resistance of incriminated bacteria over the last three years in the
      northern Togo. METHODS: From January 2007 to January 2010, 533 cerebrospinal
      fluids (CSF) samples were collected from patients suspected of meningitis in the
      Regional Hospital of Dapaong (northern Togo). After microscopic examination,
      samples were cultured for bacterial identification and antibiotic susceptibility.
      RESULTS: The study included 533 patients (306 male and 227 female) aged from 1
      day to 55 years [average age (13.00+/-2.07) years]. Bacterial isolation and
      identification were attempted for 254/533 (47.65%) samples. The bacterial species
      identified were: Neisseria meningitidis A (N. meningitidis A) (58.27%), Neisseria
      meningitidis W135 (N. meningitidis W135) (7.09%), Streptococcus pneumoniae (S.
      pneumoniae) (26.77%), Haemophilus influenza B (H. influenza B) (6.30%) and
      Enterobacteriaceae (1.57%). The results indicated that bacterial meningitis occur
      from November to May with a peak in February for H. influenzae and S. pneumoniae
      and March for Neisseriaceae. The distribution of positive CSF with regards to the
      age showed that subjects between 6 and 12 years followed by subjects of 0 to 5
      years were most affected with respective frequencies of 67.82% and 56.52%
      (P<0.001). Susceptibility tests revealed that bacteria have developed resistance
      to several antibiotics including aminosides (resistance rate >20% for both
      bacterial strains), macrolides (resistance rate > 30% for H. influenzae)
      quinolones (resistance rate >15% for H. influenzae and N. meningitidis W135).
      Over three years, the prevalence of S. pneumoniae significantly increased from
      8.48% to 73.33% (P<0.001), while the changes in the prevalence of H. influenzae B
      were not statistically significant: 4.24%, vs. 8.89%, (P = 0.233). CONCLUSIONS:
      Our results indicate that data in African countries differ depending on
      geographical location in relation to the African meningitis belt. This underlines
      the importance of epidemiological surveillance of bacterial meningitis.

PMID- 23146797
TI  - Study on small ruminant lungworms and associated risk factors in northeastern
      Iran.
AB  - OBJECTIVE: To determine the prevalence, identify the species involved and assess
      possible risk factors of lungworm infection in small ruminant slaughtered in
      abattoir of Mashhad in the northeast of Iran from October 2010-August 2011.
      METHODS: Faecal and post mortem examination were conducted on 350 and 2 500
      animals, respectively. RESULTS: The overall prevalence of lungworm infection was
      10.85% and 3.80% in coproscopic and post mortem examination respectively, and
      this difference was found to be significant. Higher prevalence of lungworm
      infection was recorded in post mortem examination in sheep (4.1%) than in goats
      (0.5%) (P< 0.05). The proportion of infection with Dictyocaulus filaria,
      Protostrongylus rufescens and mixed infection were 3.7%, 0.1% and 0.2% in sheep
      while in goats, the infection was reported with Dictyocaulus filaria (0.5%) only.
      The seasonal dynamics of lungworm infection showed that prevalence was highest in
      winter (7.8%) with a remarkable decline during the dry time (summer) (0.8%) which
      the difference was significant (P<0.001). The animals of less than one year old
      showed greater infection in post mortem examination than older animals
      significantly (P<0.001). Also, the infection rate between male and female animals
      showed significant difference (P<0.05) with prevalence rate of 4.6% and 2.0%,
      respectively. CONCLUSIONS: Due to its impact on production, emphasis should be
      given for the control and prevention of lungworm infection in this area.

PMID- 23146798
TI  - Antitrypanosomal potentials of the extract and fractions of Abrus precatorius
      seeds.
AB  - OBJECTIVE: To evaluate the in vivo trypanocidal activity of the methanol extract
      and fractions of Abrus precatorius seeds in mice. METHODS: Parasiteamia was
      induced unto mice by intraperitoneal injection of 1.25*10(5)Trypanosoma in normal
      saline. Five days when a high level of parasiteamia was established treatment
      commenced until ten days. The mice were treated with 10, 20 and 40 mg/kg bt. of
      the extract and 5 and 10 mg/kg bt. of the fraction (F(2)), respectively for 5
      days. Diminazene aceturate at the dose of 3.5 mg/kg bt. for two days was used as
      the reference drug. The level of parasitaemia and packed cell volume (PCV) of the
      animals estimated. RESULTS: At doses of 10, 20 and 40 mg/kg the crude extract
      showed a sharp reduction in the level of parasitaemia in mice compared with the
      untreated group. The mice treated with F(2) at doses of 5 and 10 mg/kg showed a
      sharp reduction in the level of parasitamia to zero in day 9, and a gradual
      recovery from the 12th day of treatment. This effect is comparable to that of the
      mice treated with 7 mg/kg of standard drug diminazene aceturate. The PCV of the
      treated showed a gradual decrease with time, but not as much as the untreated
      group. Phytochemical screening revealed the presence of glycosides, alkaloids,
      carbohydrates, tannins and proteins in the Abrus precatorius powder while F(2)
      was rich in alkaloids. CONCLUSIONS: This study shows that both the extract and
      the fractions of Abrus precatorius seeds exhibited a promising trypanocidal
      property. Alkaloids may be responsible for the observed activity.

PMID- 23146799
TI  - Protective effect of Mollugo nudicaulis Lam. on acute liver injury induced by
      perchloroethylene in experimental rats.
AB  - OBJECTIVE: To evaluate the protective effect of ethanol extract of Mollugo
      nudicaulis (M. nudicaulis) against perchloroethylene-induced hepatotoxicity.
      METHODS: The hepatoprotective activity of the ethanol extract of M. nudicaulis
      (200 mg/kg body wt) was studied in percholoroethylene (1 000 mg/kg body wt)
      induced hepatotoxicity in Wistar albino rats. The serum levels of AST, ALT, ALP,
      bilirubin and the liver content of SOD, CAT, GPx, GST, GSH, vitamin C were
      assessed to evaluate the hepatoprotective and antioxidant activities of the
      extract. The activity of the extract was compared with silymarin, a standard
      reference drug. In addition, serum urea, uric acid and creatinine levels were
      measured to evaluate the kidney function. The histopathological examination of
      the liver tissues was observed to support the biochemical parameters. RESULTS:
      The results revealed that the extract significantly (P<0.05) restored the serum
      levels of AST, ALT, ALP, bilirubin and significantly (P<0.05) increased the
      antioxidant enzymes SOD, CAT, GPx, GST, GSH, vitamin C in perchloroethylene
      induced rats to its normalcy. The biochemical observations were supported by the
      histopathological studies of the liver tissues. CONCLUSIONS: The results led to
      the conclusion that M. nudicaulis possess hepatoprotective and antioxidant
      activities against perchloroethylene-induced hepatotoxicity in rats.

PMID- 23146800
TI  - Hepatoprotective and cytoprotective properties of Hyptis suaveolens against
      oxidative stress-induced damage by CCl(4) and H(2)O(2).
AB  - OBJECTIVE: To investigate capacity of Hyptis suaveolens (H. suaveolens) methanol
      extract as an antioxidant to protect against carbon tetrachloride (CCl(4))
      induced oxidative stress, hepatotoxicity in Albino Wistar rats and cytoprotective
      effect of hydrogen peroxide (H(2)O(2)) induced cell death in HepG(2) cell line.
      METHODS: Two different doses of methanol extract of H. suaveolens were evaluated
      for the hepatoprotective activity against carbon tetrachloride (CCl(4)) induced
      hepatotoxicity in rats. Animals in Group I: served as control, group II: H.
      suaveolens (100 mL/kg b.w), group III: H. suaveolens (50 mL/kg b.w) + CCl(4) (1
      mg/kg), group IV: H. suaveolens (100 mL/kg b.w) + CCl(4) (1 mL/kg) and group V:
      CCl(4) (1 mL/kg). Histopathologic changes of liver were also evaluated.
      Cytotoxicity was also determined by 3, (4,5-dimethylthiazol-2-yl)2,5-diphenyl
      tetrazolium bromide (MTT) assay. RESULTS: Oral sigle dose treatment of CCl(4)
      produced a marked elevation in the serum levels of aspartate transaminase (AST),
      alanine transaminase (ALT), alkaline phosphatase (ALP) and Lactate dehydrogenase
      (LDH). Histopathological analysis of the liver of CCl(4)-induced rats revealed
      marked liver cell necrosis with inflammatory collections that were conformed to
      increase in the levels of SOD, GSH, GST, GR and LPO. Treatment with H(2)O(2)
      significantly induced death of HepG(2) cell. Pretreatment with H. suaveolens
      methanol extract inhibited or attenuated H(2)O(2) induced cytotoxicity.
      CONCLUSIONS: This study shows that H. suaveolens methanol extract can be proposed
      to protect the liver against CCl(4)-induced oxidative damage in rats and protect
      the cells against H(2)O(2)-induced oxidative damage in HepG(2) cells. The
      hepatoprotective and cytoprotective effects might be correlated with its
      antioxidant and free radical scavenger effects.

PMID- 23146801
TI  - Hypoglycemic effect of Octomeles sumatrana aqueous extract in streptozotocin
      induced diabetic rats and its molecular mechanisms.
AB  - OBJECTIVE: To investigate the hypoglycemic effect of the aqueous extract of
      Octomeles sumatrana (O. sumatrana) (OS) in streptozotocin-induced diabetic rats
      (STZ) and its molecular mechanisms. METHODS: Diabetes was induced by
      intraperitoneal (i.p.) injection of streptozotocin (55 mg/kg) in to male Sprague
      Dawley rats. Rats were divided into six different groups; normal control rats
      were not induced with STZ and served as reference, STZ diabetic control rats were
      given normal saline. Three groups were treated with OS aqueous extract at 0.2,
      0.3 and 0.5 g/kg, orally twice daily continuously for 21 d. The fifth group was
      treated with glibenclamide (6 mg/kg) in aqueous solution orally continuously for
      21 d. After completion of the treatment period, biochemical parameters and
      expression levels of glucose transporter 2 (Slc2a2), glucose-6-phosphatase
      (G6Pase) and phosphoenolpyruvate carboxykinase (PCK1) were determined in liver by
      quantitative real time PCR. RESULTS: Administration of OS at different doses to
      STZ induced diabetic rats, resulted in significant decrease (P<0.05) in blood
      glucose level in a dose dependent manner by 36%, 48%, and 64% at doses of 0.2,
      0.3 and 0.5 g/kg, respectively, in comparison to the STZ control values.
      Treatment with OS elicited an increase in the expression level of Slc2a2 gene but
      reduced the expression of G6Pase and PCK1 genes. Morefore, OS treated rats,
      showed significantly lower levels of serum alanine transaminase (ALT), aspartate
      aminotransferase (AST) and urea levels compared to STZ untreated rats. The
      extract at different doses elicited signs of recovery in body weight gain when
      compared to STZ diabetic controls although food and water consumption were
      significantly lower in treated groups compared to STZ diabetic control group.
      CONCLUSIONS: O. sumatrana aqueous extract is beneficial for improvement of
      hyperglycemia by increasing gene expression of liver Slc2a2 and reducing
      expression of G6Pase and PCK1 genes in streptozotocin-induced diabetic rats.

PMID- 23146802
TI  - Galactagogue effects of Musa x paradisiaca flower extract on lactating rats.
AB  - OBJECTIVE: To investigate the potential of Musa x paradisiaca (M. x paradisiaca)
      flower extracts in promoting milk production of lactating rats and its effects on
      growth of the suckling pups. METHODS: Galactagogue activity was evaluated in
      terms of quantity of milk produced from the rats treated with petroleum ether,
      ethanol or water extracts of the flower. Lactating rats (n = 5) of Spraque Dawley
      with six pups each were administered with the extracts in the amount of 500 mg/kg
      body weight, while the control rats were given an equivalent amount of distilled
      water. The rats were daily administered via oral feeding starting from Day 5
      until Day 14 and the performance of milk production was measured along the
      experimental period by weight-suckle-weight method. Results were statistically
      analyzed using SPSS by means of ANOVA at 0.05 and was expressed as their
      mean?standard deviation. The rates of pups' growth were measured as the weight
      gain along the experimental period. RESULTS: The rats treated with aqueous
      extract produced higher milk than control and ethanol groups. Aqueous extract was
      identified to increase milk production by 25%, while petroleum ether extract by
      18%. The mean of yields produced by the rats during suckling period for aqueous,
      petroleum ether, ethanol and control were 4.62+/-2.45, 4.37+/-1.93, 3.65+/-1.89
      and 3.69+/-1.79, respectively. Growth rates of pups for the rats treated with
      control, aqueous, ethanol extract and petroleum ether were (1.85+/-0.49), (1.78+/
      0.56), (1.65+/-0.46) and (1.56+/-0.42) g/pup, respectively. CONCLUSIONS: The
      present study reveals the potential of M. x paradisiaca flower to enhance milk
      production of nursing mothers which could be exploited for commercialization of
      the isolated extract.

PMID- 23146803
TI  - Antagonistic properties of seagrass associated Streptomyces sp. RAUACT-1: a
      source for anthraquinone rich compound.
AB  - OBJECTIVE: To identify the antibacterial potential of seagrass (Syringodium
      isoetifolium) associate microbes against bacterial pathogens. METHODS: Eumeration
      of microbial associates were analyzed with leaf and root samples of Syringodium
      isoetifolium. MIC and MBC were calculated for bacterial pathogens with microbial
      associates. Phylogenetic and GC-MS analysis were calculated for Actinomycetes sp.
      (Act01) which was the most potent. RESULTS: Of the isolated microbial associates
      phosphatase producing bacterial isolates were identified as maximum [(261.78+/
      35.09) CFU*10(4)/g] counts in root sample. Of the selected microbial isolates
      Actinomycete sp (Act01) showed broad spectrum of antibacterial activity against
      antibiotic resistant and fish bacterial pathogens. Phylogenetic analysis of Act01
      showed maximum identities (99%) with the Streptomyces sp. (GU5500072). The 16s
      rDNA secondary structure of Act01 showed the free energy values as -366.3
      kkal/mol. The GC-MS analysis Act01 showed maximum retention value with 23.742 RT
      and the corresponding chemical class was identified as 1, 4-dihydroxy-2-(3
      hydroxybutyl)-9, 10-anthraquinone 9, 10-anthrac. CONCLUSIONS: In conclusion,
      Streptomyces sp. (GU045544.1) from Syringodium isoetifolium could be used as
      potential antibacterial agent.

PMID- 23146804
TI  - Puerarin enhances superoxide dismutase activity and inhibits RAGE and VEGF
      expression in retinas of STZ-induced early diabetic rats.
AB  - OBJECTIVE: To investigate the effects of puerarin on the activity of superoxide
      dismutase (SOD), and expressions of advanced glycation end-product (AGE) receptor
      (RAGE) and vascular endothelial growth factor (VEGF) in retinas of streptozotocin
      (STZ)-induced early diabetic rats. METHODS: Diabetic rat models were established
      by inducing diabetes via intra-peritoneal injection of STZ. Rats were randomly
      divided into normal (control), diabetic (DM), and DM+ puerarin groups. After
      intra-gastric administration of puerarin (500 mg/kg/day for 4 weeks), levels of
      SOD and malondialdehyde (MDA) were determined in serum and retina. mRNA and
      protein expression levels of RAGE and VEGF in retinas were determined by real
      time polymerase chain reaction (RT-PCR) (mRNA) and Western blot analysis (protein
      levels). RESULTS: There was significantly lower SOD activity and significantly
      higher MDA in serum and retinas of the DM group compared with the two other
      groups (P<0.05). After treatment with puerarin, SOD activity increased and MDA
      content decreased in this group (P<0.05). mRNA and protein expression levels of
      RAGE and VEGF in the DM group were significantly higher than those of the other
      groups (P<0.05), and decreased after puerarin treatment (P<0.05). CONCLUSIONS:
      Puerarin is able to enhance SOD activity, and inhibit RAGE and VEGF expressions
      in retinas of STZ-induced early diabetic rats.

PMID- 23146805
TI  - Influence of Ginkgo biloba extract on the proliferation, apoptosis of ACC-2 cell
      and Survivin gene expression in adenoid cystic carcinoma of lacrimal gland.
AB  - OBJECTIVE: To explore the influence of extract of Ginkgo biloba (EGB) on the
      proliferation, apoptosis of ACC-2 cell and Survivin gene expression in adenoid
      cystic carcinoma (ACC) of lacrimal gland. METHODS: ACC-2 cell in human with ACC
      of lacrimal gland was in vitro cultured. MTT method was used for cell
      proliferation detection. Annexin V/PI double-staining flow cytometer was used to
      detect cell apoptosis and cell cycle. Survivin gene expression was analyzed by RT
      PCR and Western blotting. RESULTS: EGB had inhibitory effect on the proliferation
      of ACC-2 cell with significant dose-effect relationship, and there was
      statistical difference when compared with the control group (P<0.01). The
      inhibitory concentration 50 % (IC(50)) is 88 mg/L. The flow cytometer test
      indicated that EGB can gradually increase ACC-2 cell in G(0)-G(1) stage and
      decrease it in G(2)-M and S stage. With the increase of dose, the apoptosis rate
      of ACC-2 cell was obviously increased (P<0.05 or P<0.01). EGB had certain
      inhibitory effect on Survivin gene expression of ACC-2 cell, and Survivin gene
      expression was decreased with the increasing of the EGB concentration (P<0.01).
      CONCLUSIONS: EGB can effectively inhibit Survivin gene expression of ACC-2 cell
      in human with ACC of lacrimal gland, induce the apoptosis of ACC-2 cell and
      inhibit tumor cell proliferation.

PMID- 23146806
TI  - Effect of Chaiqinchengqi decoction on serum amyloid A in severe acute
      pancreatitis patients.
AB  - OBJECTIVE: To investigate the effect of Chaiqinchengqi decoction (CQCQD) on serum
      amyloid A (SAA) in severe acute pancreatitis (SAP) patients. METHODS: Thirty-five
      participants enrolled and were randomly assigned into either a treatment
      condition (n = 17, treated with CQCQD) or a control condition (n = 18, treated
      with placebo) 24 hours following the onset of the disease. No statistical
      difference was observed in either group at baseline. Upon admission, the Acute
      Physiology and Chronic Health Evaluation score II (APACHE II), SAA, serum C
      reactive protein (CRP) and interleukin-6 (IL-6) were measured, as well as on the
      first, 3rd and 7th day and were compared between the two groups. Organ
      complications, infection, operation rate, mortality and hospital stay were also
      compared. RESULTS: The duration of acute respiratory distress syndrome, acute
      hepatitis, acute renal failure, gastrointestinal failure and blood coagulation
      dysfunction were shorter in the treatment group than in those in the control
      group (P < 0.05). The secondary infection rates and the hospital fees in the
      treatment group were lower than those in the control group (P < 0.05) as well as
      length of hospital stay (P < 0.01). After 3 days of hospitalization, the
      APACHEII, score SAA levels, serum CRP and IL-6 in the treatment group was lower
      than those in the control group (P < 0.05). SAA was positively correlated with
      serum CRP (R = 0.346, P = 0.042), Ranson score (R = 0.442, P = 0.008) and serum
      IL-6 (R = 0.359, P = 0.034). The area under the receiver operating characteristic
      curve of admission SAA predict pancreatic necrosis (PN) was 0.815 (95% CI: 0.625
      0.954; P = 0.006). The best cut-off value of admission SAA was 7.85 mg/L with the
      sensitivity 84.6% and specificity 68.2%. CONCLUSIONS: The CQCQD can reduce the
      duration of organ damage through lowering the SAA in SAP patients and the SAA can
      early predict the PN and severity of SAP patients.

PMID- 23146807
TI  - Relationship between brain-derived neurotrophic factor and cognitive function of
      obstructive sleep apnea/hypopnea syndrome patients.
AB  - OBJECTIVE: To determine the relationship between the blood serum brain-derived
      neurotrophic factor (BDNF) level and cognitive function deterioration in patients
      with obstructive sleep apnea/hypopnea syndrome (OSAHS), and to explore the
      possible mechanism of cognitive impairment. METHODS: Twenty-eight male OSAHS
      patients and 14 normal males (as controls) were enrolled in the study.
      Polysomnography and the Montreal cognitive assessment (MoCA) were conducted. The
      blood serum BDNF levels were measured using ELISA. RESULTS: The OSAHS group had
      significantly decreased blood serum BDNF levels compared with the control group
      (t = -10.912, P = 0.000). The blood serum BDNF level of the subjects was
      significantly positively associated with the MoCA score (r = 0.544, P = 0.000),
      significantly negatively associated with the apnea-hypopnea index (AHI) and
      shallow sleep (S1+S2) (AHI: r = -0.607, P = 0.000; S1+S2: r = -0.768, P = 0.000),
      and significantly positively associated with the lowest SaO(2) (LSO), slow wave
      sleep (S3+S4), and rapid eye movement sleep (REM) (LSO: r = 0.566, P = 0.000;
      S3+S4: r = 0.778, P = 0.000; REM: r = 0.575, P = 0.000). CONCLUSIONS: OSAHS
      patients have significantly decreased blood serum BDNF levels compared with the
      control. Nocturnal hypoxia as well as the deprivation of slow wave sleep and REM
      may lead to the decreased serum BDNF level of OSAHS patients. This decreased
      blood serum BDNF level may contribute to the cognitive impairment in OSAHS.

PMID- 23146808
TI  - Comparison between magnitude reconstruction and phase-sensitive mR imaging in the
      detection of myocardial infarction.
AB  - OBJECTIVE: To determine the deference between phase sensitive magnetic resonance
      (MR) imaging and magnitude reconstruction to detect infracted myocardium.
      METHODS: Twenty patients (16 men; 4 women; mean age, 56 years). experienced Q
      wave myocardial infarction 2 weeks earlier were examined with a 3.0-T MR system
      10 minutes after administration of 0.1 mmol/kg body weight gadobenate
      dimeglumine. To determine the optimal TI, a TI scout sequence was used. A
      segmented 2D IR true fast imaging with steady-state precession (trueFISP)
      sequence that produces both phase-sensitive and magnitude-reconstructed images
      were used at TI values of 200-600 msec (TI values were varied in 100-msec steps)
      and at optimal TI (mean value, 330 msec). Contrast-noise ratios (CNRs) of normal
      and infarcted myocardium and the area of infarcted myocardium were determined.
      Two-tailed unpaired sample Student t test was used to compare CNRs, and area of
      infarction. RESULTS: MMean CNR phase-sensitive and magnitude-reconstructed images
      at optimal TI (mean value, 330 msec) were 6.2, and 6.1, respectively. For a TI of
      200 msec, CNR values were 5.5, and 4.2, respectively; for TI of 600 msec, CNR
      values were 5.8 and 4.3, respectively. Area of infarcted myocardium was
      underestimated on magnitude-reconstruction images (P = 0.002-0.03) for short TI
      values (ie., 200 msec) but not on phase sensitive reconstructed when compared
      with IR tureFISP images obtained at optimal TI. CONCLUSIONS: LPhase-sensitive
      image reconstruction results in reduced need for precise choice of TI and more
      consistent image quality.

PMID- 23146809
TI  - Clinical effects of comprehensive therapy of early psychological intervention and
      rehabilitation training on neurological rehabilitation of patients with acute
      stroke.
AB  - OBJECTIVE: To evaluate the clinical effects of comprehensive therapy of
      psychological intervention and rehabilitation training on the mental health of
      the patients with acute stroke. METHODS: A total of 120 patients with acute
      stroke were randomly divided into trial group and control group. Both groups were
      given the corresponding drug therapy, medical basic nursing and convention
      nursing. Besides, psychological intervention and comprehensive rehabilitation
      training were added to the trial group. SCL-90, Europ stroke scales (ESS) score
      were assessed with each patient on day 3 for the first time and on day 21 for the
      second time; Barthel index was assessed on the day 90. RESULTS: After
      psychological intervention, SCL-90 declined significantly in the trial group
      comparing with the control group, there were significant differences in the
      somatization, obsession, depression, anxiety, fear, ESS score, Barthel index and
      other psychological factors between the trial group and control group (P < 0.05).
      CONCLUSIONS: Comprehensive therapy of early psychological intervention and
      rehabilitation training can significantly improve the mental health, limb
      movement function, stress ability and activity of daily living on the patients
      with acute stroke.

PMID- 23146810
TI  - Pulmonary sequestration infected with nontuberculous mycobacteria: a report of
      two cases and literature review.
AB  - We report two cases of pulmonary sequestration infected with nontuberculous
      mycobacteria (NTM): Mycobacterium avium and Mycobacterium abscessus. Chest
      computed tomography showed pneumonic consolidation in the right lower lobe, which
      received a systemic blood supply from the descending aorta in both patients.
      Video-assisted thoracoscopic surgeries were successfully performed and
      pathological examinations revealed multiple caseating granulomas. A review of the
      literature revealed only seven previous case reports of pulmonary sequestration
      infected with NTM, and no case with Mycobacterium abscessus has been reported.

PMID- 23146811
TI  - Severe cytomegalovirus infections in immunocompetent patients at admission as
      dengue mimic: successful treatment with intravenous ganciclovir.
AB  - Cytomegalovirus (CMV) infection is associated with adverse clinical outcomes in
      immunosuppressed persons. The incidence and association of CMV reactivation with
      adverse clinical outcomes in critically ill persons lacking evidence of
      immunosuppression at ICU admission has received great attention in the practice
      of critical care medicine. Critically ill patients in ICU who had associated risk
      factors such as mechanical ventilation, severe sepsis, or blood transfusion are
      more prone to CMV activation, which in turn led to increased mortality and
      morbidity in terms of increased ICU stay, longer duration of mechanical
      ventilation, and higher rates of nosocomial infections. However, severe CMV as
      initial presentation mimicking dengue infection is rare. We recently came across
      seven cases with positive CMV serology at ICU admission, which we discuss in the
      light of current literature.

PMID- 23146812
TI  - Treatment of nutcracker syndrome with spermatic vein ligation and iliac vein
      anastomosis: case report of three cases.
AB  - Three patients with nutcracker syndrome (NCS) were enrolled in the study. Their
      clinical symptoms mainly included proteinuria and serious varicocele. Color
      Doppler ultrasound and computed tomography showed that the patients had
      constricted abdominal aortas, reduced superior mesenteric artery angles, and
      thinned left renal veins. Patients then underwent left spermatic vein ligation
      and iliac vein anastomosis. They were checked three months after their operation,
      and results showed that their sperms were improved and their proteinuria
      disappeared. The color Doppler ultrasound showed new cycle pathways. NCS clinical
      manifestations are complicated, and need combination diagnosis of symptoms and
      auxiliary examination to determine surgical indications. Ligation of spermatic
      vein and vein anastomosis can be used to treat NCS.

PMID- 23146813
TI  - Anatomy and ultrastructure of dermal glands in an adult water mite, Teutonia
      cometes (Koch, 1837) (Acariformes: Hydrachnidia: Teutoniidae).
AB  - Organization of dermal glands in adult water mites Teutonia cometes (Koch, 1837)
      was studied using light-optical, SEM and TEM methods for the first time. These
      glands are large and occur in a total number of ten pairs at the dorsal, ventral
      and lateral sides of the body. The slit-like external openings of the glands
      (glandularia) are provided with a cone-shaped sclerite, and are combined with a
      single small trichoid seta (hair sensillum), which is always situated slightly
      apart from the anterior aspect of the gland opening. Each gland is formed by an
      epithelium encompassing a very large lumen (central cavity) normally filled with
      secretion that stains in varying intensity on toluidine blue stained sections.
      The epithelium is composed of irregularly shaped secretory cells with an electron
      dense cytoplasm and infolded basal portions. The cells possess a large
      irregularly shaped nucleus and are filled with tightly packed slightly dilated
      cisterns and vesicles of rough endoplasmic reticulum (RER) with electron lucent
      contents. Dense vesicles are also present in the apical cell zone. Some cells
      undergo dissolution, occupy an upper position within the epithelium and have a
      lighter cytoplasm with disorganized RER. Muscle fibers are regularly present in
      the deep folds of the basal cell portions and may serve to squeeze the gland and
      eject the secretion into the external milieu. The structure of these dermal
      glands is compared with the previously described idiosomal glands of the same
      species and a tentative correlation with the glandularia system of water mites is
      given. Possible functions of the dermal glands of T. cometes are discussed.

PMID- 23146814
TI  - Assessment of the unattached fraction of indoor radon progeny and its
      contribution to dose: a pilot study in China.
AB  - The unattached fraction of radon progeny (f(p)) is one of the  most important
      factors for accurate evaluation of the effective dose from a unit of radon
      exposure, and it may vary greatly in different environments. For precise
      evaluation of the indoor radon exposure dose and the influence of unattached
      radon progeny, a pilot survey of f(p) in different environments was carried out
      in China with a portable and integrating monitor. The dose conversion factors for
      radon progeny are calculated with LUDEP((r)) code, and the dose contributions
      from the unattached and the attached radon progenies were simultaneously
      evaluated based on the results of field measurements. The results show that even
      though the concentrations of radon progeny vary significantly among different
      indoor environments, the variations of f(p) seem relatively small (9.3-16.9%).
      The dose contribution from unattached radon progeny is generally larger (30.2
      46.2%) in an indoor environment.

PMID- 23146815
TI  - Determination of organic compounds in landfill leachates treated by Fenton
      Adsorption.
AB  - The objective of this study was to identify the organic compounds removed from
      the leachate when treated with Fenton-Adsorption by gas chromatography coupled to
      mass spectrometry (GC-MS) in order to identify toxic compounds that could be
      harmful for the environment or human health. The physicochemical characterization
      of the raw leachate was carried out before and after the Fenton-Adsorption
      process. The effluent from each stage of this process was characterized: pH,
      Biological Oxygen Demand (BOD(5)), Chemical Oxygen Demand (COD), Total Organic
      Carbon (TOC), Total Carbon (TC), Inorganic Carbon (IC), Total Solids (TS), Total
      Suspended Solids (TSS) and Color. The organic compounds were determined by GC-MS.
      The removal of COD and color reached over 99% in compliance with the Mexican
      Standard NOM-001-SEMARNAT-1996, which establishes the maximum permissible limits
      for contaminants present in wastewater discharges to water and national goods.
      The chromatographic analysis from the Fenton-Adsorption effluent proved that this
      treatment removed more than 98% of the organic compounds present in the initial
      sample. The mono (2-ethylhexyl) ester 1,2-benzenedicarboxylic acid persisted,
      although it is not considered as toxic compound by the NOM-052-SEMARNAT-2005.
      Therefore, the treated effluent can be safely disposed of into the environment.

PMID- 23146816
TI  - Pharmacokinetics of single ascending doses of the P-glycoprotein inhibitor
      tariquidar in healthy subjects.
AB  - We assessed the pharmacokinetics (PK), tolerability and safety of tariquidar
      (TQD), a P-glycoprotein (Pgp) inhibitor, after intravenous administration of
      single ascending doses. Employed doses were up to 4-fold higher than in previous
      clinical trials in cancer patients and are capable of inhibiting Pgp at the blood
      brain barrier. Fifteen male healthy volunteers were randomized to receive single
      intravenous doses of TQD at 4, 6 or 8 mg/kg body weight and underwent blood
      sampling for over 24 h. TQD concentrations were determined in plasma samples with
      high-performance liquid chromatography mass spectrometry. No dose-limiting
      toxicities of TQD were observed. The area under the plasma concentration-time
      curve from start until 24 h after the end of infusion was positively correlated
      with an administered TQD dose (r = 0.8981, p < 0.0001). Moreover, we found a
      positive correlation for volume of distribution at steady state (r = 0.7129, p =
      0.0004) with TQD dose. Dose dependency of volume of distribution at steady state
      points to non-linear PK of TQD, which was in all likelihood caused by transporter
      saturation at high TQD doses. Acceptable safety and tolerability as well as dose
      linear increases in plasma exposure support the future use of TQD at doses up to
      8 mg/kg to inhibit Pgp at the human blood-brain barrier.

PMID- 23146817
TI  - In vitro performance of different methods in detecting occlusal caries lesions.
AB  - Early caries detection is essential for the implementation of preventive,
      therapeutic and intervention strategies within general dental practice.
      OBJECTIVE: The aim of this study was to compare the in vitro performance of the
      International Caries Detection and Assessment System (ICDAS), digital photographs
      scored with ICDAS (ICDAS photographs), fibre-optic transillumination (FOTI),
      optical coherence tomography (OCT), SoproLife((r)) camera and two implementations
      of quantitative light-induced fluorescence a commercial (QLF-Inspektor Research
      systems) and a custom (QLF-Custom) system, to detect early and intermediate
      occlusal lesions. METHODS: One hundred and twelve permanent extracted teeth were
      selected and assessed with each detection method. Histological validation was
      used as a gold standard. The detection methods were compared by means of
      sensitivity, specificity, areas under receiver operating characteristic (AUROC)
      curves for enamel and dentine levels and with the Spearman's rank correlation
      coefficient against histology. RESULTS: For any enamel or dentine caries
      detection, the AUROC curves ranged from 0.86 (OCT) to 0.98 (ICDAS and ICDAS
      photographs, SoproLife((r)) camera) and at the dentine level from 0.83 (OCT) to
      0.96 for FOTI. The correlations with histology ranged between 0.65 (OCT) and 0.88
      (ICDAS and FOTI). Under in vitro conditions, the assessed detection methods
      showed excellent intra-examiner reproducibility. All the methods were strongly
      correlated with histology (p<0.01) except OCT which showed a moderate correlation
      (0.65). CONCLUSION: Even though all methods present similar performance in
      detecting occlusal caries lesions, visual inspection seems to be sufficient to be
      used in clinical practice for detection and assessment of lesion depth. Other
      methods may be useful in monitoring caries lesion behaviour.

PMID- 23146818
TI  - Hormone replacement therapy after endometrial cancer.
AB  - Endometrial cancer is the fourth most common female cancer in the UK and the most
      common gynaecological cancer. Quality of life and symptom control needs to be
      considered in women who enter a surgically induced menopause. Hormone replacement
      in this population has been controversial to date. The current evidence regarding
      the safety of estrogen only and combined hormone replacement therapy is discussed
      in this review. The use of topical vaginal therapies, alternate therapies and the
      current data regarding testosterone use for symptom control is also outlined.

PMID- 23146819
TI  - Identification and functional characterization of a large deletion of the CYP11B1
      gene causing an 11beta-Hydroxylase deficiency in a Chinese pedigree.
AB  - BACKGROUND: Steroid 11beta-hydroxylase deficiency (11OHD) is the second most
      common cause of congenital adrenal hyperplasia. Inherited in an autosomal
      recessive manner, 11OHD is caused by mutations in the CYP11B1 gene. OBJECTIVE: To
      identify the mutation causing 11OHD in a Chinese pedigree and analyze the
      functional consequences and phenotype associated with this mutation. METHODS: A
      Chinese family with 11OHD was screened for mutations in the CYP11B1 gene. Mini
      gene experiment was performed to mimic the natural splicing and outcome of the
      genetic variation. RESULTS: Complete DNA sequencing of the CYP11B1 gene revealed
      a novel 449-bp homozygous deletion (g.2697del449) in the patient and a
      heterozygous deletion in both of the patient's parents and sister. This mutation
      was predicted to lead to the skipping of part of exon 3 and all of exon 4 and
      inserting of part of intron 4 in the CYP11B1 mRNA. It generated a truncated
      protein and resulted in the complete destruction of the heme-binding domain of
      the enzyme. CONCLUSIONS: The novel deletion drastically affects normal protein
      structure and abolishes normal enzyme activity, leading to a severe phenotype of
      congenital adrenal hyperplasia due to 11OHD.

PMID- 23146821
TI  - The relatively good outcome of cerebellum-brainstem ischemic strokes.
AB  - BACKGROUND: Our clinical experience suggests that the outcome of cerebellum
      brainstem ischemic strokes is better than that of hemispheric ischemic strokes.
      METHODS: Within the setting of 2 national Israeli prospective stroke surveys, we
      analyzed risk factors, etiology, severity at presentation, and prognosis of first
      ischemic cerebellum-brainstem stroke (259 patients), comparing with strokes
      within the anterior circulation (1,029 patients). RESULTS: Patients with
      cerebellum-brainstem strokes were younger and had less frequently atrial
      fibrillation and congestive heart failure. Cardioembolic etiology was
      significantly less prevalent (p < 0.001). Severity at presentation was milder (p
      < 0.001). At discharge, worsening of the modified Rankin Scale was present in a
      smaller number of patients (p < 0.001); more returned to their home (p < 0.001).
      Six-month and 1-year mortality were lower (p < 0.001 for both). Adjusted logistic
      regression models showed that patients with cerebellum-brainstem strokes had 50%
      smaller chances of dying (OR 0.55; 95% CI 0.31-0.98) and a smaller chance of
      worsening of the modified Rankin Scale at discharge (OR 0.61; 95% CI 0.46-0.82).
      CONCLUSIONS: Cerebellum-brainstem strokes are less frequently cardioembolic, have
      a less severe presentation, and carry a better immediate and long-term prognosis.

PMID- 23146820
TI  - Can oral fluid cannabinoid testing monitor medication compliance and/or cannabis
      smoking during oral THC and oromucosal Sativex administration?
AB  - OBJECTIVES: We characterize cannabinoid disposition in oral fluid (OF) after
      dronabinol, synthetic oral Delta(9)-tetrahydrocannabinol (THC), and Sativex, a
      cannabis-extract oromucosal spray, and evaluate whether smoked cannabis relapse
      or Sativex compliance can be identified with OF cannabinoid monitoring. METHODS:
      5 and 15 mg synthetic oral THC, low (5.4 mg THC, 5.0 mg cannabidiol (CBD)) and
      high (16.2 mg THC, 15.0 mg CBD) dose Sativex, and placebo were administered in
      random order (n=14). Oral fluid specimens were collected for 10.5 h after dosing
      and analyzed for THC, CBD, cannabinol (CBN), and 11-nor-9-carboxy-THC (THCCOOH).
      RESULTS: After oral THC, OF THC concentrations decreased over time from baseline,
      reflecting residual THC excretion from previously self-administered smoked
      cannabis. CBD and CBN also were rarely detected. After Sativex, THC, CBD and CBN
      increased greatly, peaking at 0.25-1 h. Median CBD/THC and CBN/THC ratios were
      0.82-1.34 and 0.04-0.06, respectively, reflecting cannabinoids' composition in
      Sativex. THCCOOH/THC ratios within 4.5 h post Sativex were <= 1.6 pg/ng, always
      lower than after oral THC and placebo. THCCOOH/THC ratios increased throughout
      each dosing session. CONCLUSIONS: Lack of measurable THC, CBD and CBN in OF
      following oral THC, and high OF CBD/THC ratios after Sativex distinguish oral and
      sublingual drug delivery routes from cannabis smoking. Low THCCOOH/THC ratios
      suggest recent Sativex and smoked cannabis exposure. These data indicate that OF
      cannabinoid monitoring can document compliance with Sativex pharmacotherapy, and
      identify relapse to smoked cannabis during oral THC medication but not Sativex
      treatment, unless samples were collected shortly after smoking.

PMID- 23146822
TI  - Sonographic monitoring of midline shift predicts outcome after intracerebral
      hemorrhage.
AB  - BACKGROUND: Spontaneous intracerebral hemorrhage (ICH) and the evolution of
      subsequent perihemorrhagic edema lead to midline shift (MLS), which can be
      assessed by transcranial duplex sonography (TDS). In this observational study, we
      monitored MLS with TDS in patients with supratentorial ICH up to day 14 after the
      ictus, and then correlated MLS with the outcome 6 months after hospital
      discharge. METHODS: Sixty-eight patients with spontaneous ICH (volume >20 cm(3))
      were admitted during a 1-year period between April 2009 and April 2010. Sixty-one
      patients fulfilled the inclusion criteria and were eligible for analysis. TDS to
      measure MLS was performed upon admission and then subsequently, using serial
      examinations in 24-hour intervals up to day 14. Statistical tests were used to
      determine cut-off values for functional outcome and mortality after 6 months.
      RESULTS: The median National Institutes of Health Stroke Scale (NIHSS) score upon
      admission was 21 and the mean hematoma volume was 52 cm(3). NIHSS score,
      functional outcome, hematoma volume and MLS were correlated in the examined
      patient cohort. ICH score upon admission, hematoma volume and the extent of MLS
      on days 1-14 were predictive of functional outcome and death. Values of MLS
      showed two peaks, the first between day 2 and day 5 and the second between day 12
      and day 14, indicating that edema progresses not only during the acute but also
      during the subacute phase. Depending on the time point, an MLS of 4.5-7.5 mm or
      greater indicated an impending failure of conservative therapy. An MLS of 12 mm
      or greater at any time indicated mortality with a sensitivity of 69%, a
      specificity of 100% and positive and negative predictive values of 100 and 74%,
      respectively. CONCLUSIONS: MLS seems to be a crucial factor for outcome after
      ICH. Apart from the hematoma volume itself, edema adds to the intracranial
      pressure. To monitor MLS in early patient management after ICH, TDS is a useful
      noninvasive bedside alternative, avoiding increased radiation exposure and
      repeated transportation of critically ill patients. Cut-off values may help to
      reliably predict functional outcome and treatment failure in patients undergoing
      maximal neurointensive therapy.

PMID- 23146823
TI  - On the operational quantity H(p)(3) for eye lens dosimetry.
AB  - In the past the operational quantity H(p)(3) has been defined for calibration
      purposes in a slab phantom. Recently, an additional phantom in the form of a
      cylinder was suggested for eye lens dosimetry as a cylinder much better
      approximates the shape of a head than a slab. Therefore, this work investigates
      whether the quantity H(p)(3), when defined in the respective calibration phantom,
      adequately estimates the eye lens dose (or is at least conservative) depending on
      the phantom: it turns out that in most cases both calibration phantoms are
      similarly well suited. Finally, the definition of the eye lens dose is discussed
      together with possible consequences on the definition of H(p)(3): the
      consideration of only the radiation sensitive volume of the lens causes H(p)(3)
      not to be conservative in beta radiation fields.

PMID- 23146825
TI  - Effect of gum tragacanth exuded by three Iranian Astragalus on mixed milk protein
      system during acid gelation.
AB  - The effects of various concentrations of three species of gum tragacanth on the
      gelation process, microstructure and viscoelastic properties of milk protein
      mixed gels acidified at 37 degrees C by glucono-delta-lactone (GDL) were
      investigated using dynamic rheometry and microscopy. According to rheological
      measurements, the addition of gum tragacanth in the range of 0.05-0.2% (w/w) into
      milk protein dispersions led to a weaker structure for the milk protein network,
      compared to the control sample. This weakening effect could be eliminated by
      adding 0.3% (w/w) gum tragacanth exudates from A. gossypinus; the compositional
      features of gum tragacanth may have been responsible for the improved protein
      protein interactions, greater structural strength and reduced gelation time
      onset. It was determined by scanning electron microscopy that the addition of gum
      tragacanth at a low concentration caused the density of the matrix to increase,
      while an open structure was observed in the presence of a higher gum
      concentration.

PMID- 23146824
TI  - Review: Effect of drugs on human cough reflex sensitivity to inhaled capsaicin.
AB  - Capsaicin, the pungent extract of red peppers, has been used in clinical
      research for almost three decades. Capsaicin has gained favor as the provocative
      agent of choice to measure cough reflex sensitivity, as it induces cough in a
      safe, reproducible, and dose-dependent manner. One of the major uses of capsaicin
      cough challenge testing has been to evaluate the effect of a pharmacological
      intervention on the human cough reflex. The current review summarizes the
      published experience with capsaicin inhalation challenge in the evaluation of
      drug effects on cough reflex sensitivity. A notable contrast evident between
      studies demonstrating a drug effect (inhibition of cough reflex sensitivity) and
      those that do not, is the predominance of healthy volunteers as subjects in the
      latter. This observation suggests that subjects with pathological cough, rather
      than normal volunteers, comprise the optimal group in which to evaluate the
      effect of potential antitussive agents on human cough reflex sensitivity.

PMID- 23146826
TI  - Coronary CT angiography and possible acute coronary syndromes: a new opportunity
      for on call radiologists to wake up at night?

PMID- 23146827
TI  - Cervical chordoma with moderate bone impairment in a child. Answer to October E
      quid.

PMID- 23146828
TI  - Understanding TB latency using computational and dynamic modelling procedures.
AB  - The Mycobacterium tuberculosis bacilli's potency to cause persistent latent
      infection that is unresponsive to the current cocktail of TB drugs is strongly
      associated with its ability to adapt to changing intracellular environments, and
      tolerating, evading and subverting host defence mechanisms. We applied a
      combination of bioinformatics and mathematical modelling methods to enhance the
      understanding of TB latency dynamics. Analysis of time course microarray gene
      expression data was carried out and gene profiles for bacilli adaptation and
      survival in latency, simulated by hypoxia were determined. Reverse network
      engineering techniques were used to predict gene dependencies and regulatory
      interactions. Biochemical systems theory was applied to mathematically model the
      inferred gene regulatory networks. Significant regulatory genes involved in
      latency were determined by a combination of systems biology procedures and
      mathematical modelling of the inferred regulatory networks. Analysis of gene
      clusters of the inferred networks in the stationary and non-replicating phases of
      the bacilli predicted probable functions of some of the latency genes to be
      associated with latency genes of known functions. The systems biology approach
      and mathematical computational deletion experiments predicted key genes in the TB
      latency/dormancy program that may be possible TB drug targets. However, these
      gene candidates require experimental testing and validation.

PMID- 23146829
TI  - Amino acid substitutions in the Hepatitis C virus core region of genotype 1b in
      Moroccan patients.
AB  - The aim of the present study was to identify basic amino acid in the core region
      in subtype 1b-infected, treatment-naive patients from Morocco and to search for
      their eventual association with liver cancer. The survey included 151 patients
      (86 patients with chronic hepatitis and 65 patients with hepatocellular
      carcinoma, HCC). We performed direct sequencing, and compared the data obtained
      with the consensus sequence of core protein. Several recurrent amino acid
      substitutions were observed. The Arg70 was changed for a Gln in 22 of 112
      patients (19.6%) and Leu91 was changed to Met in 23 of 112 patients (20.5%).
      Besides, the threonine at position 75 (Thr75) was mutated for alanine or serine
      in 43 (38.4%) and 40 (35.7%) of the patients, respectively. Overall, there was no
      significant difference between patients with chronic hepatitis and those with HCC
      regarding amino acids substitution number (24% vs. 33%, respectively, P = 0.457).
      Our study provides the first inventory of predominant amino acid substitutions in
      the HCV core region genotype 1b. The impact of single or combined mutations on
      the resistance to treatment or on disease progression is still unknown and
      deserves more attention in the future.

PMID- 23146830
TI  - Population cytogenetic and molecular evidence for existence of a new species in
      Anopheles fluviatilis complex (Diptera: Culicidae).
AB  - Anopheles fluviatilis James, an important malaria vector in the Oriental region
      has been established as a complex of at least three cryptic species which vary in
      their biological characteristics and malaria transmission potential. The sibling
      species S, T and U of Fluviatilis Complex can be identified by examination of
      species-specific fixed inversions in the polytene chromosomes and can also be
      differentiated by an allele-specific PCR assay based on differences in the D3
      region of 28S ribosomal DNA (rDNA) of these species. Here we report a new An.
      fluviatilis population from villages under Laksar Community Health Centre,
      District Haridwar (Uttarakhand state), India which differs from the three sibling
      species of Fluviatilis Complex by two fixed paracentric inversions, s(1) and S in
      polytene chromosome arms 2 and 3 respectively. Longitudinal study carried out in
      study villages showed that the new cytotype was sympatric with species T and U in
      all the collections and no inversion heterozygotes were observed between them.
      Thus presence of two fixed paracentric inversions in polytene chromosomes with
      total absence of inversion heterozygotes demonstrates reproductive isolation
      which unequivocally establishes this cytological variant as a new species,
      provisionally designated as species V in the Fluviatilis Complex. Analysis of DNA
      sequences of D3 domain of 28S rDNA and ITS 2 region has also shown that species V
      is distinctly different from species S, T and U. With the discovery of new
      species in the Fluviatilis Complex, in-depth studies are required to know its
      distribution pattern and biological characteristics and to ascertain its role in
      malaria transmission.

PMID- 23146831
TI  - Co-circulation of pandemic 2009 H1N1, classical swine H1N1 and avian-like swine
      H1N1 influenza viruses in pigs in China.
AB  - The pandemic A/H1N1 influenza viruses emerged in both Mexico and the United
      States in March 2009, and were transmitted efficiently in the human population.
      They were transmitted occasionally from humans to other mammals including pigs,
      dogs and cats. In this study, we report the isolation and genetic analysis of
      novel viruses in pigs in China. These viruses were related phylogenetically to
      the pandemic 2009 H1N1 influenza viruses isolated from humans and pigs, which
      indicates that the pandemic virus is currently circulating in swine populations,
      and this hypothesis was further supported by serological surveillance of pig sera
      collected within the same period. Furthermore, we isolated another two H1N1
      viruses belonging to the lineages of classical swine H1N1 virus and avian-like
      swine H1N1 virus, respectively. Multiple genetic lineages of H1N1 viruses are co
      circulating in the swine population, which highlights the importance of intensive
      surveillance for swine influenza in China.

PMID- 23146832
TI  - Evolution of complementary nucleotides in 5' and 3' untranslated regions of
      influenza A virus genomic segments.
AB  - The genome of influenza A virus comprises 8 segments (segments 1-8) of single
      stranded RNA (virion RNA: vRNA) with negative-polarity. All vRNAs share 13 and 12
      terminal nucleotides in the 5' and 3' untranslated regions (UTRs), respectively,
      which are partially complementary and constitute panhandle and corkscrew
      structures. Here, it is shown, from the analysis of genomic sequences for 506
      strains of influenza A virus, that the number of contiguous complementary
      nucleotides in the 5' and 3' UTRs varies from 4 to 7 among segments.
      Complementary nucleotides were segment specific and highly conserved in all
      segments except for segment 6, where in the phylogenetic analysis co-evolution
      was observed to have occurred between and within subtypes of neuraminidase (NA).
      Mutations in the terminal sequences sometimes appeared to have caused convergence
      between subtypes, involving changes in multiple nucleotide positions. These
      observations suggest that intra-segmental (homologous) recombinations may have
      taken place for transferring terminal sequences in segment 6.

PMID- 23146833
TI  - Enhanced lysophosphatidylcholine and sphingomyelin contents are characteristic of
      spermatozoa from obese men-A MALDI mass spectrometric study.
AB  - The lipids of human spermatozoa are characterized by unique fatty acyl
      compositions, i.e. considerable amounts of highly unsaturated, in particular
      docosahexaenoyl (22:6) fatty acyl residues. This makes spermatozoa very sensitive
      to oxidation. It has already been shown that the most abundant lipid of sperm,
      phosphatidylcholine (PC), is converted into lysophosphatidylcholine (LPC) under
      conditions of oxidative stress, and, thus, the PC/LPC ratio may be used as a
      measure of sperm quality. However, direct correlations between the PC/LPC ratios
      and certain pathologies are so far missing. We will show here for the first time
      (by using matrix-assisted laser desorption and ionization time-of-flight (MALDI
      TOF) mass spectrometry (MS)) that sperm from obese donors (BMI>35kg/m(2)) are
      characterized by (a) a significantly increased LPC as well as (b) an increased
      sphingomyelin content. This does exclusively hold true for the lipid extracts of
      the spermatozoa but is not valid for the related seminal fluids.

PMID- 23146834
TI  - High-dose calcitriol, docetaxel and zoledronic acid in patients with castration
      resistant prostate cancer: a phase II study.
AB  - INTRODUCTION: Docetaxel has become the standard chemotherapy for patients with
      castration-resistant prostate cancer (CRPC). We wanted to assess the efficacy and
      safety of a weekly high-dose calcitriol, docetaxel and zoledronic acid
      combination in CRPC. PATIENTS AND METHODS: Thirty patients were enrolled to
      receive calcitriol 0.5 ug/kg orally in 4 divided doses over 4 h on day 1 of each
      treatment week, docetaxel 36 mg/m(2) i.v. infusion on day 2 of each treatment
      week and zoledronic acid 4 mg i.v. on day 2 of the first and fifth week of each
      cycle. Treatment was administered weekly for 6 consecutive weeks on an 8-week
      cycle. RESULTS: Out of 23 evaluable patients, there was a response of prostate
      specific antigen (PSA) in 11 patients (47.8%); 6 (26.1%) had a stable PSA level
      for a median of 4.2 months. The median survival time was 15 months (95%
      confidence interval 13.9-16.1 months). The regimen was generally tolerated;
      anemia was the only grade 3/4 hematological toxicity in 2 patients. CONCLUSIONS:
      This regimen was tolerated, and half of the patients had a PSA response. Although
      our response rates are inferior to some studies using docetaxel, we believe our
      response rates are acceptable knowing that we are treating CRPC, which still has
      variable outcomes.

PMID- 23146836
TI  - Diversity, assembly and regulation of archaeal type IV pili-like and non-type-IV
      pili-like surface structures.
AB  - Archaea have evolved fascinating surface structures allowing rapid adaptation to
      changing environments. The archaeal surface appendages display such diverse
      biological roles as motility, adhesion, biofilm formation, exchange of genetic
      material and species-specific interactions and, in turn, increase fitness of the
      cells. Intriguingly, despite sharing the same functions with their bacterial
      counterparts, the assembly mechanism of many archaeal surface structures is
      rather related to assembly of bacterial type IV pili. This review summarizes our
      state-of-the-art knowledge about unique structural and biochemical properties of
      archaeal surface appendages with a particular focus on archaeal type IV pili-like
      structures. The latter comprise not only widely distributed archaella (formerly
      known as archaeal flagella), but also different highly specialized archaeal pili,
      which are often restricted to certain species. Recent findings regarding assembly
      mechanisms, structural aspects and physiological roles of these type IV pili-like
      structures will be discussed in detail. Recently, first regulatory proteins
      involved in transition from both planktonic to sessile lifestyle and in assembly
      of archaella were identified. To conclude, we provide novel insights into
      regulatory mechanisms underlying the assembly of archaeal surface structures.

PMID- 23146835
TI  - Alteration of the serum N-glycome of mice locally exposed to high doses of
      ionizing radiation.
AB  - Exposure of the skin to ionizing radiation leads to characteristic reactions that
      will often turn into a pathophysiological process called the cutaneous radiation
      syndrome. The study of this disorder is crucial to finding diagnostic and
      prognostic bioindicators of local radiation exposure or radiation effects. It is
      known that irradiation alters the serum proteome content and potentially post
      translationally modifies serum proteins. In this study, we investigated whether
      localized irradiation of the skin alters the serum glycome. Two-dimensional
      differential in-gel electrophoresis of serum proteins from a man and from mice
      exposed to ionizing radiation showed that potential post-translational
      modification changes occurred following irradiation. Using a large-scale
      quantitative mass-spectrometry-based glycomic approach, we performed a global
      analysis of glycan structures of serum proteins from non-irradiated and locally
      irradiated mice exposed to high doses of gamma-rays (20, 40, and 80 Gy). Non
      supervised descriptive statistical analyses (principal component analysis) using
      quantitative glycan structure data allowed us to discriminate between
      uninjured/slightly injured animals and animals that developed severe lesions.
      Decisional statistics showed that several glycan families were down-regulated
      whereas others increased, and that particular structures were statistically
      significantly changed in the serum of locally irradiated mice. The observed
      increases in multiantennary N-glycans and in outer branch fucosylation and
      sialylation were associated with the up-regulation of genes involved in
      glycosylation in the liver, which is the main producer of serum proteins, and
      with an increase in the key proinflammatory serum cytokines IL-1beta, IL-6, and
      TNFalpha, which can regulate the expression of glycosylation genes. Our results
      suggest for the first time a role of serum protein glycosylation in response to
      irradiation. These protein-associated glycan structure changes might signal
      radiation exposure or effects.

PMID- 23146837
TI  - Metagenomics of microbial life in extreme temperature environments.
AB  - Microbial life in extreme environments is attracting broad scientific interest.
      Knowledge about it helps in defining the boundaries for life to exist, and
      organisms living under extreme conditions are also interesting sources for
      enzymes with unusual and desirable properties. The tremendous progress in DNA
      sequencing technologies now makes it relatively easy to gain a representative
      overview of the composition of such communities, and many community studies have
      in the last decade applied metagenomics to characterize habitats extreme in, for
      example, temperature, salt and acidity. The future challenges in the field are
      likely to become more and more related to the conversion of the expected massive
      amounts of sequence information into an understanding of the corresponding
      biological community functions.

PMID- 23146839
TI  - Male mating behaviour in relation to female sexual swellings, socio-sexual
      behaviour and hormonal changes in wild Barbary macaques.
AB  - In many cercopithecine primates females display probabilistic cues of fertility
      to indicate the periovulatory period to males. These cues may include female
      behaviour, acoustic signals, and morphological signs such as the anogenital
      swelling. However, the extent to which males can utilise this information varies
      between species. We describe male sexual behaviour in relation to changes in
      anogenital swelling size, timing of ovulation and female socio-sexual behaviour
      in wild Barbary macaques (Macaca sylvanus). We further compare male sexual
      behaviour during conception and post-conception cycles to evaluate if males
      differentiate between these qualitatively different cycle types. Our results show
      that during conception cycles male mating behaviour was concentrated around the
      fertile phase implying that males inferred information from more than swelling
      size alone. Male mating frequency increased in line with female socio-sexual
      behaviour, namely female presenting and the frequency of copulations with
      copulation calls. Most strikingly our results show that males invested equally in
      mating during fertile and non-fertile, i.e. post-conception, maximum swelling
      phases. Whether post-conception swellings were merely a result of changes in
      hormone concentrations during pregnancy or part of a female reproductive strategy
      remains elusive. In sum, this study adds to the body of research on the evolution
      of female sexual signals and how males may infer information from these cues.

PMID- 23146840
TI  - Prospective analysis of falls in dominant ataxias.
AB  - In a previous retrospective study, we demonstrated that falls are common and
      often injurious in dominant spinocerebellar ataxias (SCAs) and that nonataxia
      features play an important role in these falls. Retrospective surveys are plagued
      by recall bias for the presence and details of prior falls. We therefore sought
      to corroborate and extend these retrospective findings by means of a prospective
      extension of this fall study. 113 patients with SCA1, SCA2, SCA3 or SCA6,
      recruited from the EuroSCA natural history study, were asked to keep a fall diary
      in between their annual visits to the participating centres. Additionally,
      patients completed a detailed questionnaire about the first three falls, to
      identify specific fall circumstances. Relevant disease characteristics were
      retrieved from the EuroSCA registry. 84.1% of patients reported at least one fall
      during a time period of 12 months. Fall-related injuries were common and their
      frequency increased with that of falls. The presence of nonataxia symptoms was
      associated with a higher fall frequency. This study confirms that falls are a
      frequent and serious complication of SCA, and that the presence of nonataxia
      symptoms is an important etiological factor in its occurrence.

PMID- 23146838
TI  - Influence of ovarian and non-ovarian estrogens on weight gain in response to
      disruption of sweet taste--calorie relations in female rats.
AB  - Regulation of energy balance in female rats is known to differ along a number of
      dimensions compared to male rats. Previous work from our lab has demonstrated
      that in female rats fed dietary supplements containing high-intensity sweeteners
      that may disrupt a predictive relation between sweet tastes and calories, excess
      weight gain is demonstrated only when females are also fed a diet high in fat and
      sugar, and is evidenced primarily in animals already prone to gain excess weight.
      In contrast, male rats show excess weight gain when fed saccharin-sweetened
      yogurt supplements when fed both standard chow diets and diets high in fat and
      sugar, and regardless of their proneness to excess weight gain. The goal of the
      present experiments was to determine whether ovarian, or other sources of
      estrogens, contributes to the resistance to excess weight gain in female rats fed
      standard chow diets along with dietary supplements sweetened with yogurt. Results
      of the first experiment indicated that when the ovaries were removed surgically
      in adult female rats, patterns of weight gain were similar in animals fed
      saccharin-sweetened compared to glucose-sweetened yogurt supplements. In the
      second experiment, when the ovaries were surgically removed in adult female rats,
      and local production of estrogens was suppressed with the aromatase inhibitor
      anastrozole, females fed the saccharin-sweetened yogurt consumed more energy and
      gained more weight than females fed the glucose-sweetened yogurt. However, when
      the ovaries were surgically removed prior to the onset of puberty (at 24-25 days
      of age), females given saccharin-sweetened yogurt along with vehicle gained
      excess weight. In contrast, weight gain was similar in those given saccharin
      sweetened and glucose-sweetened yogurt along with anastrozole. The results
      suggest that behavioral differences between males and females in response to
      disruption of sweet->calorie relations may result from differences in patterns of
      local estrogen production. These differences may be established developmentally
      during the pubertal period in females.

PMID- 23146841
TI  - Effect of mycophenolic acid on cyclosporin A-induced fibronectin expression in
      rat mesangial cells.
AB  - This study was undertaken to determine if mycophenolic acid (MPA) inhibits the
      profibrotic action of cyclosporin A (CsA) and, if so, to determine the molecular
      mechanisms involved. The effect of MPA treatment on CsA-induced signaling through
      the transforming growth factor-beta (TGF-beta)/Smad pathway was evaluated by
      immunoblot analysis in cultured primary rat mesangial cells. Treatment of cells
      with 1 umol/l MPA did not significantly decrease the CsA-induced expression of
      TGF-beta(1), but partially reversed the increases in Smad3 phosphorylation and
      fibronectin (FBN) production, and increased Smad7 expression. These results
      suggest that MPA may ameliorate CsA-induced FBN production by modulating the Smad
      signaling pathway. This study provides evidence that MPA can attenuate CsA
      induced renal injury after kidney transplantation.

PMID- 23146842
TI  - Structural bioinformatics of the general transcription factor TFIID.
AB  - The Transcription Factor IID is a large macromolecular complex composed of the
      TATA-box binding protein (TBP) and a group of 13-14 conserved TBP-associated
      factors (TAFs). TAFs are known to regulate transcription at various levels -
      mediating transcription via interaction with activators, histone modifications;
      recognition and binding to promoters; acting as a platform for other
      Transcription Factors and RNA polymerase II. Despite numerous previous studies of
      the TFIID complex, the knowledge concerning the structure of its components, and
      thus the exact mechanism of its function, remains undetermined. To carry out an
      in-depth analysis of TFIID we performed the structural bioinformatic analysis of
      the TFIID complex. The sequence identity and similarity of 13.74% and 37.56%,
      respectively (calculated with PAM250 matrix) between M1 aminopeptidase protein
      and TAF2 and the high similarity of their putative secondary structures allowed
      us to model a large part of the TAF2 structure. The sequence analysis enabled the
      mapping of previously not fully characterized structural domains in well-studied
      TAF proteins (including the full histone domains of TAF4 and 12 or TAF3 and 8).
      In this study we provided detailed structural models for all the elements of
      human analyzed in the context of TFIID activity, along with indications of
      structural alterations within TFIID in various animal model species.

PMID- 23146843
TI  - [Humanities in radiologia].

PMID- 23146844
TI  - Biological prosthetics for hernia repair.

PMID- 23146845
TI  - Laparoscopic repair of ventral hernia.
AB  - OBJECTIVE: To determine the outcome of patients in terms of wound complications
      and follow-up, after laparoscopic ventral hernia repair. STUDY DESIGN: A case
      series study. PLACE AND DURATION OF STUDY: Department of Surgery, Dubai Hospital,
      Dubai, from January 2007 to December 2011. METHODOLOGY: All patients above 13
      years of age, who underwent laparoscopic ventral hernia repair, were included. A
      proceed dual mesh was used for repair of hernia. Multiple parameters were
      analyzed, including demographic features, presentations, co-morbid conditions,
      duration of hernia, and defect size. The duration of surgery, postoperative
      complications, and follow-up of these patients in terms of suture site pain and
      recurrence of hernia were also analyzed. The data was expressed as frequency,
      percentages and mean +/- standard deviation of values. RESULTS: There were 27
      patients with mean age of 47 +/- 10.3 years, including 20 female (74.07%) and 7
      male (25.95%)patients. All patients presented with abdominal wall swelling. The
      hernia was partially reducible in 12 patients (44.44%), and completely reducible
      in 15 patients (55.55%). Seven patients (25.95%) had hypertension, 4 (14.81%) had
      ischaemic heart disease, and 4 (14.81%) had obesity as co-morbid conditions. All
      patients underwent laparoscopic hernia repair with proceed dual mesh. The mean
      defect size of the hernia was 6 cm, and mean duration of surgery was 94 minutes.
      Early postoperative complications included, seroma in 3 patients (11.11%), and
      haematoma in one patient (3.70%). The mean follow-up was 23 months. Four patients
      (14.81) had pain at suture site. CONCLUSION: Laparoscopic repair is an
      appropriate approach for ventral hernia repair. It results in good repair and low
      wound complications in terms of haematoma and wound infection. There was no
      recurrence of hernia in this study.

PMID- 23146846
TI  - Peripheral artery disease in type II diabetes.
AB  - OBJECTIVE: To determine the frequency of peripheral arterial disease (PAD) in
      type 2 diabetic patients. STUDY DESIGN: Cross-sectional observational study.
      PLACE AND DURATION OF STUDY: Diabetes Clinic, Medical Unit III, Jinnah
      Postgraduate Medical Centre, Karachi, from January to June 2010. METHODOLOGY:
      Three hundred and eighty seven (387) type II diabetic patients of either gender
      and any age were included in the study. Patients with a previous history of
      trauma to the arterial vasculature, pregnancy and those who underwent arterial
      graft procedures were excluded. Non-purposive convenient sampling technique was
      used to enroll patients in the study. PAD was diagnosed when ankle-brachial index
      (ABI) was less than 0.9. A p-value of less than 0.05 was considered statistically
      significant. RESULTS: Out of 387 studied patients, 128 were males (33.1%) and 259
      were females (66.9%). Mean age was 52.22 +/- 9.671 (22 - 76) years in the entire
      cohort. Mean duration of diabetes was 9.38 +/- 6.39 years. PAD was detected in
      152 (39.28%) of the total study subjects. Thirty-one of 128 male patients
      (24.22%) had PAD disease while 121 out of 259 female patients (46.71%) had
      evidence of PAD (p = 0.001). Hypertension was a significantly associated factor
      (p = 0.002). CONCLUSION: A high frequency of PAD was observed in the diabetic
      population particularly with hypertension and more prevalent in females.

PMID- 23146847
TI  - Effects of Ibuprofen on orthotopic glioma model in rats.
AB  - OBJECTIVE: To determine the effects of ibuprofen (Ibp) on the vessel
      proliferation and necrosis in a rat glioma model. STUDY DESIGN: Experimental,
      randomized interventional trial. PLACE AND DURATION OF STUDY: 1st Neurosurgery
      Clinic in Bakirkoy Mental Diseases Hospital, Bakirkoy, Istanbul, Turkey, in the
      year 2010. METHODOLOGY: After stereotactic injection of C6/LacZ rat glioma cells
      into the Wistar rats brain, the rats were randomly assigned to two treatment
      groups (group 1, control; group 2, Ibp treatment). Rats were sacrificed 18 days
      after treatment, and number of intra-/peri-tumoural vessels, microendothelial
      proliferations, immunohistochemistry and necrotic area were evaluated. RESULTS:
      Ibp treatment significantly decreased tumour tissue, intratumoral vessel number
      and total tumour area level. The level of Ki67 was significantly decreased in the
      tumour tissue of group 2. Additionally, the total necrotic area / total tumour
      volume (%) was significantly less in the tumour tissue of the ibuprofen-treated
      rats compared to the controls. CONCLUSION: The data show that the Ibp produced an
      important reduction in glioma tumour cell proliferation in the rat model.

PMID- 23146848
TI  - Association of gestational weight gain and pre-pregnancy body mass index with
      adverse pregnancy outcome.
AB  - OBJECTIVE: To determine the association between gestation weight gain (GWG) and
      adverse pregnancy outcome in a Pakistani population. STUDY DESIGN: Analytical
      study. PLACE AND DURATION OF STUDY: The Aga Khan University, Karachi, from
      February 2003 to 2007. METHODOLOGY: This study used secondary data of 4,735 women
      from a large cohort study on fetal growth. Pre-pregnancy BMI was categorized
      according to the recommendations from the institute of medicine (IOM, 2009) and
      gestation weight gain (GWG) was noted. Chi-square test was used to find the
      association of GWG and pre-pregnancy BMI with low birth weight (LBW), preterm
      delivery, large for gestational age (LGA), and caesarean section. Logistic
      regression analysis was performed to control for confounders like age, parity,
      working status and ethnicity. RESULTS: The prevalence of LBW decreased with
      increasing BMI. GWG of the population was noted as 8.5 kg. LBW was observed to
      have an inverse relationship with GWG. Women below the age of 19 were twice more
      likely to have LBW than above 35 years of age. Weight gain above the recommended
      range were twice more likely to have large for dates.Overweight women were 1.5
      times more likely to deliver preterm whereas obese women were 1.4 times more
      likely to undergo caesarean section than women with normal BMI. CONCLUSION: The
      optimal weight gain was estimated to be 8.5 kg to prevent low birth weight in our
      population. Obese women are more likely to have LGA, caesarean sections and pre
      term deliveries.

PMID- 23146849
TI  - Frequency and management of raised intraocular pressure following intravitreal
      triamcinolone acetonide.
AB  - OBJECTIVE: To determine the frequency and management of intraocular pressure
      (IOP) elevation following intravitreal triamcinolone acetonide (IVTA). STUDY
      DESIGN: Case series. PLACE AND DURATION OF STUDY: Isra Postgraduate Institute of
      Ophthalmology/Al-Ibrahim Eye Hospital, Karachi, from May 2007 to May 2008.
      METHODOLOGY: In this study, 198 eyes of 150 patients requiring IVTA injection,
      were included. Pre-injection assessment comprised of detailed history, general
      and ocular examination including anterior and posterior segment examination with
      IOP measurements with Goldmann tonometer. After informed consent, IVTA 4 mg/0.1
      ml was injected through pars plana and IOP was measured at 1 week, 1 month, 3
      months and 6 months and if raised, treated accordingly. RESULTS: Out of 150
      patients, 82 were male (54.7%) and 68 were female (45.3%) (M: F = 1.2: 1). Mean
      age was 50.61 +/- 10.59 years. Raised IOP value after IVTA, higher than 21 mmHg
      was observed at one week in 28 eyes (14.1%), at 1 month n 48 eyes (24.2%), at 3
      months in 76 eyes (38.4%) and at 6 months in 25 eyes (12.6%). Raised IOP was
      controlled by topical beta blockers alone or in combination with carbonic
      anhydrase inhibitors in 58 eyes (76.3%). CONCLUSION: Elevation of IOP after IVTA
      injection occurred in 76 eyes (38.3%). It may take an extended period of time to
      manifest raised IOP. In majority of the patients, raised IOP was managed with
      topical medications.

PMID- 23146850
TI  - Posterior assisted levitation (PAL) by using Akahoshi/Wahab irrigating pars plana
      levitator.
AB  - OBJECTIVE: To assess the outcome of irrigating Akahoshi/Wahab pars plana
      levitator for posterior assisted levitation in dropped nucleus during
      phacoemulsification. STUDY DESIGN: A case series. PLACE AND DURATION OF STUDY:
      Ophthalmology Unit-III, Dow University of Health Sciences at Sindh Government
      Lyari General Hospital and Al-Noor Eye Hospital, Karachi, from January 2008 to
      December 2009. METHODOLOGY: Cases of dropped nucleus during phacoemulsification
      were recruited. Predisposing factors and stage of phacoemulsification at which
      dropped nucleus were recognized. Levitator was inserted through pars plana after
      vitrectomy around nucleus and levitation was carried out. Follow-up was done till
      6 months. RESULTS: Thirty two patients including 18 males (56.3%) and 14 females
      (43.8%) underwent pars plana levitation. Predisposing factors were pupillary
      miosis in 9 cases, Brunescent cataract in 7 cases, pseudoexfoliation in another 7
      cases, hypermature cataract in 5 cases and extended capsulorrhexis in 4 cases.
      Posterior capsular rent occurred in 22 (68.8%) cases while zonular dehiscence /
      rupture were found in 10 cases (31.3%). Nuclei were dropped during quadrant
      aspiration in 10 cases (31.3%) and during chopping in 8 cases (25%). Another 5
      cases (15.6%) occurred during each hydrodissection and chopping while 4 cases
      (12.5%) were found during sculpting of nuclei. Final best corrected visual acuity
      was 6/12 and better in 22 cases (68.8%) while in 10 cases (31.3%) it was 6/18 to
      6/36. No complication related to pars plana levitator was observed. CONCLUSION:
      Posterior assisted levitation of dropped nucleus during phacoemulsification by
      irrigating Akahoshi/Wahab pars plana levitator is a fast and safe surgical
      technique.

PMID- 23146851
TI  - Autologous fascia graft as a biological barrier to silicone application in
      rabbits.
AB  - OBJECTIVE: To determine the cellular effects of providing a fascial interface
      around subcutaneously-placed silicone implants, in terms of capsule thickness,
      myofibroblast/fibroblast cell count and inflammatory cell count. STUDY DESIGN:
      Interventional, comparative study. PLACE AND DURATION OF STUDY: Istanbul
      University Cerrahpasa Medical Faculty, Laboratory of Experimental Animals,
      Istanbul, Turkey, from May to September 2008. METHODOLOGY: A total of 16 adult
      New Zealand male rabbits with mean weight of 2508 +/- 360 g were used in the
      study. Animals were divided into two groups as experiment and control groups with
      equal number of rabbits in each. Fascia injection was applied on silicone implant
      in the experiment group and compared with the control group in terms of capsule
      thickness, myofibroblast/fibroblast cell count and inflammatory cell count. At
      the end of the experiment, tissue samples were examined macroscopically and
      microscopically for the above. Statistical analysis of data was performed using
      student's t-test. RESULTS: A statistically significant difference was found
      between experiment group and control group in terms of mean capsule thickness,
      mean myofibroblast and fibroblast cell counts and cell density (p < 0.05, each).
      CONCLUSION: Fascia tissue barrier prevent silicone rod reaction and foreign body
      reaction developing against silicone prosthesis in the studied animal model.

PMID- 23146852
TI  - Diagnostic utility of anti-citrullinated protein antibody and its comparison with
      rheumatoid factor in rheumatoid arthritis.
AB  - OBJECTIVE: To assess the diagnostic utility of anti-citrullinated protein
      antibody (anti-CCP) in rheumatoid arthritis (RA) and compare it with rheumatoid
      factor (RF). STUDY DESIGN: Analytical study. PLACE AND DURATION OF STUDY: Section
      of Chemical Pathology, Department of Pathology and Microbiology and Medicine, the
      Aga Khan University, Karachi, from January to May 2010. METHODOLOGY: A review of
      medical records of patients presenting to the clinics with complaints of muscular
      or joint pains and who were tested for their serum anti-CCP was done. Inclusion
      criteria were presence of clinical synovitis in at least one joint and an absence
      of alternative diagnosis. Patients with arthralgia alone or with missing acute
      phase reactants information were excluded. Scoring and classification of RA was
      done using the 2010 RA Classification Criteria by the American College of
      Rheumatology (ACR). RESULTS: Out of the 98 charts reviewed, ACR criteria showed
      54 cases with RA. The mean age of the group was 46 +/- 15 years, 82.7% being
      females. High titers of anti-CCP corresponded with the ACR scores. The
      sensitivity and specificity of anti-CCP and RF reactivity for the diagnosis of RA
      were 54.7% and 95.5% versus 59.3% and 88.4% respectively. CONCLUSION: Anti-CCP is
      useful for the diagnosis of RA due to its higher specificity as compared to RF
      and can predict disease severity.

PMID- 23146853
TI  - Retention and processing methods of nasal prosthesis.
AB  - Patients with congenital malformations, traumatic or pathological mutilation and
      maxillofacial developmental disorders can be restored aesthetically and
      emotionally by the production and use of facial prostheses. The aim of this study
      was to review the literature about the retention and processing methods of facial
      prostheses, and discuss their characteristics. A literature review on Medline
      (PubMed) database was performed by using the keywords "maxillofacial prosthesis,
      silicone,  esin, pigment, cosmetic, prosthetic nose", based on articles published
      from 1956 to 2010. Several methods of retention, from adhesives to the placement
      of implants, and different processing methods such as laser, CAD/CAM and rapid
      prototyping technologies have been reported. There are advantages and
      disadvantages of each procedure, and none can be classified as better compared to
      others.

PMID- 23146854
TI  - Anaesthetic management of a young patient with homocystinuria.
AB  - Homocystinuria is a rare autosomal recessive genetic disease. It is caused by a
      deficiency in cystathionine-b-synthase leading to a defect in methionine
      metabolism. High levels of plasma homocysteine are associated with vascular
      injury via mechanisms of oxidative damage, vascular smooth muscle proliferation,
      promotion of platelet activation and aggregation,and disruption of normal
      procoagulant-anticoagulant balance favouring thrombosis. This is a case of 8
      years old boy, a known case of homocystinuria, who was scheduled for bilateral
      lensectomy and intraocular lens placement. The major anaesthetic considerations
      include the development of thromboembolism, need to avoid nitrous oxide in
      balanced anaesthesia regimen and hypoglycaemia.

PMID- 23146855
TI  - Synovial sarcoma of the heart.
AB  - A young male presented with dyspnoea and was found to have a diastolic murmur at
      the left lower sternal edge. Transthoracic and transoesophageal echocardiograms
      found a large mass attached to the tricuspid valve, which was projecting into the
      right atrium and the right ventricle. The mass was causing significant
      obstruction of the right ventricular inflow. Emergency surgery had to be
      performed because the patient developed severe vomiting (of unknown cause)
      leading to haemodynamic compromise. This condition was not responding to fluid
      resuscitation as there was obstruction to right ventricular inflow.
      Intraoperatively the mass was removed and the tricuspid valve was repaired. The
      histological and immunohistochemical examination of the excised tissue confirmed
      the rare diagnosis of synovial sarcoma of the heart.Postsurgical imaging showed
      no metastases. The patient received postoperative radio therapy and chemotherapy.
      The tumour recurred after 6 months and the patient succumbed to his illness and
      expired.

PMID- 23146856
TI  - Primary carcinoma of ectopic breast tissue in axilla.
AB  - A 30 years old married lady presented with 4 x 5 cm, firm, non-tender, mobile
      swelling on anterior wall of left axilla. FNAC revealed carcinoma. The
      examination of breast including axillary tail, arm, chest and abdomen did not
      reveal any abnormality. Mammogram and MRI of both breasts did not reveal any
      lesion in the breast including axillary tail. Local wide excision along with
      axillary clearance was carried out. Final histopathology revealed invasive ductal
      carcinoma (Grade II) of axillary breast tissue and one, out of the recovered
      lymph nodes, was involved by the tumour. The immunohistochemistry also confirmed
      the findings.

PMID- 23146857
TI  - Fibrous dysplasia of mandible.
AB  - An elderly male presented to the ENT, Outpatient Department at Abbasi Shaheed
      Hospital (ASH) with a mass on the left side of the face and lower jaw for 8 - 9
      years. It was of a tennis ball size. No treatment was sought by him during those
      years. A diagnosis of benign fibro-osseous lesion of the mandible was made. Later
      the histopathology proved the same. he first occurrence in a male gender and
      involvement of the mandible is uncommon.

PMID- 23146858
TI  - Multifocal venous thrombosis in Behcet's disease.
AB  - Behcet's disease is a multisystem inflammatory vascular disorder with a chronic
      course characterized by recurrent oral and genital ulcers, eye lesion, arthritis
      and skin lesions. It has a typically waxing and waning course. The cause and
      pathogenesis of the disease are unclear and specific treatment is not available.
      A 39 years old man presented with rash, ocular manifestation and left leg
      swelling. He was found to have deep venous thrombosis of left leg along with
      recurrent cerebral venous thrombosis. He was a known case of Behcet's disease
      since 3 years and had been on anticoagulants since then.

PMID- 23146859
TI  - Transanal protrusion of a ventriculoperitoneal shunt catheter.
AB  - A two years old boy presented with a transanal protrusion of the
      ventriculoperitoneal (VP) shunt catheter. A VP shunt was inserted when the boy
      was six-month-old for congenital hydrocephalus. He was active and neurologically
      normal, with no signs of meningitis and peritoneal irritation. During laparotomy,
      the tube was seen entering the sigmoid colon, so the tube was cut at the point
      where it entered the sigmoid colon. The distal end of the protruding tube was
      pulled out from the anus. The sigmoid colon was repaired, and a delayed shunt
      revision was completed. The patient was discharged without abdominal and
      neurological deterioration.

PMID- 23146860
TI  - Interferon-induced central retinal vein thrombosis.
AB  - A middle-aged lady presented with sudden onset of unilateral central retinal vein
      thrombosis after completing 6 months course of interferon and ribavirin for
      chronic hepatitis C infection. She had no risk factors and all her thrombophilia
      workup was normal, however, she was found to be dyslipidemic which may have
      contributed to atherosclerosis and predispose to thrombosis. Despite
      anticoagulation, her visual acuity deteriorated. This case illustrates the
      possibility of unpredictable visual complication of interferon. Frequent eye
      examination should be undertaken in patients having underlying risk factors like
      diabetes, hypertension or dyslipidemia undergoing interferon therapy.

PMID- 23146861
TI  - Colchicine and NSAID combination causing acute kidney injury.
AB  - Colchicine is used mainly for the treatment of gout and familial mediterranean
      fever. The use of colchicine is limited by its toxicity, and colchicine overdose
      is associated with a high mortality rate. Herein, we are reporting a young man
      who presented to the emergency department after ingesting 13.5 mg of colchicine
      and 1200 mg of aceclofenac (non-steroid anti-inflammatory drug) for deliberate
      self harm. He developed acute kidney injury, metabolic acidosis, and bradycardia
      after admission. A combination effect of non-steroid anti-inflammatory drug and
      colchicines was responsible for this event.

PMID- 23146862
TI  - Severe haemolytic anaemia due to ingestion of naphthalene (mothball) containing
      coconut oil.
AB  - Naphthalene, a widely used industrial and household chemical, has rarely been an
      agent of poisoning worldwide. Severe haemolysis from naphthalene poisoning is
      rare and can be a challenge to clinicians. We report a 22-year-old female, who
      accidentally ingested naphthalene mixed coconut oil and got admitted with
      recurrent vomiting, headache and passage of dark urine. Severe intravascular
      haemolysis with hypotension and neutrophilic leukocytosis was detected. She was
      treated with red blood cell transfusions, intravenous saline infusion and
      ascorbic acid.

PMID- 23146863
TI  - Frequency of HBsAg positivity: a laboratory data analysis.
AB  - The objective of the study was to evaluate the current frequency ratio of HBsAg
      seropositivity in a laboratory-based setting. It was a retrospective study,
      conducted during September 2009 and November 2010 at Dr. Essa's Diagnostic
      Laboratory and its branches in Karachi, Pakistan. Blood samples of 8,648
      individuals were screened for HBsAg using the BioRad EVOLIS EIA method. Pertinent
      questionnaires filled in by 50 practicing physicians were also evaluated. The 551
      subjects (6.4%) that tested positive for HBsAg included 360 males (65.3%) and 191
      females (34.6%). The highest frequency of HBsAg was noted in those aged 16 - 29
      years (43.9%). HBsAg rate in the studied population has steadily increased and is
      more common in the sexually active age group, with males tending to be more often
      seropositive than females.

PMID- 23146864
TI  - Abnormally prominent coracoid processes in a malnourished patient with spinal
      cord injury.

PMID- 23146865
TI  - Evaluation of the RENAL nephrometry scoring system in adopting nephron-sparing
      surgery for cT1 renal cancer.
AB  - OBJECTIVE: The RENAL nephrometry scoring system characterizes tumors according to
      their size, growth pattern, location and nearness to the renal sinus or
      collecting system. The current study aims to evaluate the RENAL nephrometry
      scoring system in adopting nephron-sparing surgery (NSS) for cT1 renal cancer.
      METHODS: Clinicopathological data of 200 consecutive patients who had undergone
      radical nephrectomy (RN) or NSS for clinical stage T1 renal cell cancer at our
      single institution during 2005-2009 were investigated retrospectively. RESULTS:
      Of 200 patients, 103 were scheduled for RN, whereas 97 were planned to undergo
      NSS, 9 of whom actually underwent RN. Those who were planned to undergo NSS were
      younger and had smaller tumors (p < 0.001). The median RENAL score was
      significantly lower among those who were originally assigned to NSS (5, range 4
      10) versus RN (8, range 4-11) (p < 0.001). Three months after surgery, the renal
      function of patients who had been scheduled for NSS was significantly better than
      in those treated by RN (p < 0.001). CONCLUSIONS: This study suggests that the
      RENAL nephrometry scoring system is a useful tool in adopting NSS for cT1 renal
      cancer and that objective decision-making for NSS was possible.

PMID- 23146866
TI  - A systematic review of sperm donors: demographic characteristics, attitudes,
      motives and experiences of the process of sperm donation.
AB  - BACKGROUND This systematic review aimed first to integrate the current body of
      knowledge on the demographic, institutional and psychosocial information on sperm
      donors, and second to provide insight into the actual experiences of men who
      donate and the attitudes towards potential donation.  METHODS Electronic
      databases (PUBMED, CINAHL, PsycINFO, Embase and Web of Science) were searched
      with no date restriction using a specific search strategy followed by a snowball
      strategy. English language peer-reviewed abstracts and full texts were screened
      for eligibility and the risk of bias was assessed with 15 criteria. Eligibility,
      quality assessments and data extraction were performed by two independent
      researchers, resolving disagreement by discussion.  RESULTS The initial search
      retrieved 857 studies and after quality assessment, 29 studies were retained for
      data extraction. Data from nine countries were obtained. The review synthesis
      revealed differences and similarities between actual and potential sperm donors
      on demographic characteristics, financial compensation and attitudes towards
      anonymity, disclosure and providing information to potential offspring. A number
      of methodological shortcomings have been identified in the studies investigating
      sperm donors.  CONCLUSIONS Institutional factors (such as recruitment procedures,
      altruism versus compensation of sperm donors, anonymity versus open-identity
      donation) and the impact of changing legislation have largely dominated the
      studies on sperm donation. Furthermore, studies from countries with a bias
      towards white Western ideology and interpretation were over-represented. This has
      resulted in a profile of potential and actual sperm donors in terms of
      demographics, recruitment strategies, motivation for donation and attitudes
      regarding anonymity, disclosure, recipients and offspring. However, the
      psychosocial needs and experiences of the donor, and their follow-up and
      counselling are largely neglected. This review has identified key issues to
      inform current practice and the development of pathways of care for sperm donors
      that reflect the multidimensional nature of sperm donation.

PMID- 23146867
TI  - Reproductive assistance in HIV serodiscordant couples.
AB  - BACKGROUND: Three quarters of individuals infected with human immunodeficiency
      virus (HIV) are in their reproductive years and may consider pregnancy planning.
      Techniques have been developed which can minimize the risk of HIV transmission in
      these couples, and the current literature on this topic is reviewed here.
      METHODS: We reviewed the literature for the following topics: risk of HIV
      transmission, effects of HIV infection on fertility, reproductive assistance in
      industrialized and low-income countries, pre-exposure chemoprophylaxis (PrEP) and
      timed intercourse in HIV-discordant couples for both male and female positivity.
      Relevant publications were identified through searches of the EMBASE Medline and
      PubMed databases, the Google-indexed scientific literature and periodic
      specialized magazines from the on-line Library Service of the University of
      Milan, Italy. RESULTS: In serodiscordant couples in which the man is positive,
      the primary method used to prevent HIV transmission is 'sperm washing', followed
      by IUI or IVF. Data show that sperm washing in HIV-positive men has not produced
      seroconversion in women or their offspring; however, the evidence is limited.
      Recently, increasing evidence describing PrEP for HIV prevention has been
      published and PrEP could be an alternative to ART for fertile couples. Usually
      HIV-infected women undergo self-insemination around the time of ovulation. Few
      studies have been published on IVF outcome in HIV-infected women. CONCLUSIONS:
      Assisted reproduction programmes should be integrated into global public health
      services against HIV. For HIV serodiscordant couples with infected men, sperm
      washing should be the first choice. However, timed intercourse and PrEP for HIV
      prevention has been reported. Recent data highlight the possible impairment of
      fertility in HIV-infected women. Efforts to design a multicentric study should be
      strengthened.

PMID- 23146868
TI  - Clinical features, surgical treatment and long-term outcome in adult patients
      with Moyamoya disease in China.
AB  - BACKGROUND: Moyamoya disease (MMD) develops mostly in Asian countries including
      Japan, Korea, mainland China and Taiwan. However, there are few detailed
      demographic and clinical data about Chinese patients with MMD. Currently, the
      most effective treatment in adult patients with MMD is unknown. There have only
      been a few small case series reporting on encephaloduroarteriosynangiosis (EDAS)
      in an adult population. Here we describe the clinical features, surgical
      treatment and long-term outcome of adults with MMD treated at a single
      institution in China. METHODS: Our cohort included 470 adult patients with MMD.
      The demographic and clinical characteristics were obtained by retrospective chart
      review and long-term outcome was evaluated using the stroke status. The modified
      Rankin Scale (mRS) was used to determine the neurological functional outcome.
      Univariate and multivariate logistic regression analyses were performed to
      determine risk factors for postoperative morbidity and functional outcome. The
      risk of subsequent stroke was determined using the Kaplan-Meier method and Cox
      regression was used to determine risk factors for postoperative or subsequent
      strokes. RESULTS: The median age for the onset of symptoms was 36.8 (range, 18
      59) years. The ratio of female to male patients was 1:1 (231/239). Familial
      occurrence of MMD was 2.3%. The most common initial symptom was a cerebral
      ischemic event. The incidence of postoperative ischemic events or hemorrhage was
      5.9% (9.8% of patients). Older age at symptom onset, posterior cerebral artery
      (PCA) involvement and the presence of transient ischemic attack (TIA) were
      identified as predictors of adverse postoperative events. The Kaplan-Meier
      estimate stroke risk was 10.1% in the first 2 years, and the 5-year Kaplan-Meier
      risk of stroke was 13% after surgery for all patients treated with surgical
      revascularization. Older age at symptom onset, PCA involvement and the presence
      of TIA were identified as predictors of postoperative or subsequent strokes.
      Overall, 73.2% of patients had an independent life with no significant
      disability, with the strongest predictor being the preoperative mRS score.
      CONCLUSION: Clinical characteristics of adult MMD in China are different from
      those in other Asian countries. EDAS in adult patients with MMD carries a low
      risk, is effective at preventing future ischemic events and improves quality of
      life.

PMID- 23146869
TI  - IgG4-related disease underlying the pathogenesis of coronary artery disease.
AB  - Immunoglobulin G4 (IgG4)-related disease is a newly emerging clinicopathological
      entity that is characterized by increased serum IgG4 levels and tissue
      infiltration of IgG4-positive plasma cells. IgG4-related immune inflammation has
      been reported to be present in inflammatory aortic aneurysm, albeit not in every
      case. Several recent studies have suggested that IgG4-related disease may
      underlie certain coronary artery abnormalities, such as coronary aneurysm,
      pseudotumor, wall calcification, and intimal thickening. Here, what is known
      about IgG4-related coronary artery lesions, as well as questions that remain to
      be answered thus far, are discussed.

PMID- 23146870
TI  - Salivary proteomics in biomedical research.
AB  - Proteins that are important indicators of physiological or pathological states,
      can provide information for the identification of early and differential markers
      for disease. Saliva, contains an abundance of proteins, offers an easy,
      inexpensive, safe, and non-invasive approach for disease detection, and possesses
      a high potential to revolutionize the diagnostics. Discovery of salivary
      biomarkers could be used to scrutinize health and disease surveillance. The
      impact of human saliva proteome analysis in the search for clinically relevant
      disease biomarkers will be realized through advances made using proteomic
      technologies. The advancements of emerging proteomic techniques have benefited
      biomarker research to the point where saliva is now recognized as an excellent
      diagnostic medium for the detection of disease. This review presents an overview
      of the value of saliva as a credible diagnostic tool and we aim to summarize the
      proteomic technologies currently used for global analysis of saliva proteins and
      to elaborate on the application of saliva proteomics to the discovery of disease
      biomarkers, and discuss some of the critical challenges and perspectives in this
      field.

PMID- 23146873
TI  - Current world literature.

PMID- 23146871
TI  - Manganese transport via the transferrin mechanism.
AB  - Excessive manganese (Mn) uptake by brain cells, particularly in regions like the
      basal ganglia, can lead to toxicity. Mn(2+) is transported into cells via a
      number of mechanisms, while Mn(3+) is believed to be transported similarly to
      iron (Fe) via the transferrin (Tf) mechanism. Cellular Mn uptake is therefore
      determined by the activity of the mechanisms transporting Mn into each type of
      cell and by the amounts of Mn(2+), Mn(3+) and their complexes to which these
      cells are exposed; this complicates understanding the contributions of each
      transporter to Mn toxicity. While uptake of Fe(3+) via the Tf mechanism is well
      understood, uptake of Mn(3+) via this mechanism has not been systematically
      studied. The stability of the Mn(3+)Tf complex allowed us to form and purify this
      complex and label it with a fluorescent (Alexa green) tag. Using purified and
      labeled Mn(3+)Tf and biophysical tools, we have developed a novel approach to
      study Mn(3+)Tf transport independently of other Mn transport mechanisms. This
      approach was used to compare the uptake of Mn(3+)Tf into neuronal cell lines with
      published descriptions of Fe(3+) uptake via the Tf mechanism, and to obtain
      quantitative information on Mn uptake via the Tf mechanism. Results confirm that
      in these cell lines significant Mn(3+) is transported by the Tf mechanism
      similarly to Fe(3+)Tf transport; although Mn(3+)Tf transport is markedly slower
      than other Mn transport mechanisms. This novel approach may prove useful for
      studying Mn toxicity in other systems and cell types.

PMID- 23146872
TI  - Molecular portrait-based correlation between primary canine mammary tumor and its
      lymph node metastasis: possible prognostic-predictive models and/or stronghold
      for specific treatments?
AB  - BACKGROUND: This study aimed to evaluate the relationship between the molecular
      phenotype of the primary mammary tumor and its related lymph node metastasis in
      the dog to develop prognostic-predictive models and targeted therapeutic options.
      RESULTS: Twenty mammary tumor samples and their lymph node metastases were
      selected and stained by immunohistochemistry with anti-estrogen receptor (ER), 
      progesterone receptor (PR), -human epidermal growth factor receptor 2 (c-erbB-2),
      -cytokeratin 5/6 (CK 5/6), -cytokeratin 14 (CK14), -cytokeratin 19 (CK 19) and 
      protein 63 (p63) antibodies. Four phenotypes (luminal A, luminal B, c-erbB2
      overexpressing and basal-like) were diagnosed in primary tumors and five (luminal
      A, luminal B, c-erbB-2 overexpressing, basal-like and normal-like) in the lymph
      node metastases. Phenotypic concordance was found in 13 of the 20 cases (65%),
      and seven cases (35%) showed discordance with different lymph node phenotypic
      profile from the primary tumor. CONCLUSIONS: The phenotype of the primary tumor
      assumes a predictive-therapeutic role only in concordant cases, meaning that both
      the primary tumor and its lymph node metastasis should be evaluated at the same
      time. A treatment plan based only on the primary tumor phenotype could lead to
      therapeutic failures if the phenotype of the lymph node metastasis differs from
      that of the primary tumor.

PMID- 23146875
TI  - Respiratory signaling of locus coeruleus neurons during hypercapnic acidosis in
      the bullfrog, Lithobates catesbeianus.
AB  - The locus coeruleus (LC) in the brainstem senses alterations in CO(2)/pH and
      influences ventilatory adjustments that restore blood gas values to starting
      levels in bullfrogs (Lithobates catesbeianus). We hypothesized that neurons of
      the bullfrog LC are sensitive to changes in CO(2)/pH and that chemosensitive
      responses are intrinsic to individual neurons. In addition, we hypothesized
      putative respiratory control neurons of the bullfrog LC would be stimulated by
      hypercapnic acidosis within physiological ranges of P(CO(2))/pH. 84% of LC
      neurons depolarized and increased firing rates during exposure to hypercapnic
      acidosis (HA). A pH dose response curve shows LC neurons from bullfrogs increase
      firing rates during physiologically relevant CO(2)/pH changes. With chemical
      synapses blocked, half of chemosensitive neurons lost sensitivity to HA; however,
      gap junction blockade did not alter chemosensitive responses. Intrinsically
      chemosensitive neurons increased input resistance during HA. These data
      demonstrate that majority of neurons within the bullfrog LC elicit robust firing
      responses during physiological DeltaCO(2)/pH, likely enabling adjustment of acid
      base balance through breathing.

PMID- 23146876
TI  - The language network.
AB  - Language processing is supported by different regions located in separate parts
      of the brain. A crucial condition for these regions to function as a network is
      the information transfer between them. This is guaranteed by dorsal and ventral
      pathways connecting prefrontal and temporal language-relevant regions. Based on
      functional brain imaging studies, these pathways' language functions can be
      assigned indirectly. Dorsally, one pathway connecting the temporal cortex (TC)
      and premotor cortex supports speech repetition, another one connecting the TC and
      posterior Broca's area supports complex syntactic processes. Ventrally, the
      uncinate fascile and the inferior fronto-occipital fascile subserve semantic and
      basic syntactic processes. Thus, the available evidence points towards a neural
      language network with at least two dorsal and two ventral pathways.

PMID- 23146877
TI  - Sleepiness at the time of testing impairs olfactory performance.
AB  - BACKGROUND: We aimed to investigate the differential roles of hypocretin versus
      dopamine dysfunction versus excessive daytime sleepiness (EDS) in the development
      of hyposmia. Olfaction in patients with Parkinson disease, restless leg syndrome,
      narcolepsy with cataplexy, EDS, and healthy controls was compared. METHODS: Sixty
      six subjects participated in the study: 14 with PD, 13 with NC, 12 with RLS, 8
      with EDS, and 20 healthy controls. Olfaction was tested using standardized
      Sniffin'Sticks test. Sleepiness was assessed using Karolinska, Stanford and
      Epworth sleepiness scales. RESULTS: Olfactory discrimination correlated
      negatively with subjective momentary sleepiness. A significant deficit in
      olfaction was found in PD patients with respect to all other groups in all
      olfactory domains. No significant differences were found between the other
      groups. CONCLUSION: We could not confirm decreased olfaction in patients with NC.
      Yet the significant correlation between momentary sleepiness and olfactory
      function suggests that sleepiness is a potential confounding factor in the
      assessment of olfaction, e.g. in NC. Furthermore, our results confirm that
      olfaction is impaired in PD, whereas it is normal in RLS.

PMID- 23146878
TI  - Novel anti-inflammatory effects of doxazosin in rodent models of inflammation.
AB  - BACKGROUND: Doxazosin is an alpha(1)-adrenergic receptor antagonist for the
      treatment of high blood pressure and benign prostatic hyperplasia. Peripheral
      alpha-adrenergic receptors have been implicated in inflammation. AIM: To examine
      the anti-inflammatory effects of doxazosin in rodent models of inflammation.
      METHOD: The anti-inflammatory properties of doxazosin were investigated in 4
      models. In all studies, drug treatment was administered 15 min prior to
      challenge. In the lipopolysaccharide (LPS)-induced systemic inflammation model,
      LPS was injected systemically at 0.25 mg/kg. At 90 min after challenge, blood
      samples were collected for analysis. In the LPS-induced pulmonary inflammation
      model, LPS was instilled intranasally. Four hours after challenge, the lungs were
      harvested for monocyte chemoattractant protein-1 (MCP-1) analysis. In a delayed
      type hypersensitivity model, the mice were injected intravenously with sheep red
      blood cells, and rechallenged in the left footpad 7 days later. Drug treatment
      was given on day 6 and 7 just prior to the rechallenge. The thickness of hind
      footpads was measured at 15 min after rechallenge. In the thioglycollate-induced
      peritoneal monocyte infiltration model, mice were challenged with 3%
      thioglycollate, and 2 h later peritoneal lavage fluid was collected for MCP-1
      analysis. RESULTS: In animals challenged systemically and intranasally with LPS,
      doxazosin inhibited TNF-alpha and MCP-1 production, respectively. In the delayed
      type hypersensitivity model, footpad swelling was inhibited by doxazosin.
      Doxazosin decreased the level of MCP-1 release in the peritoneal cavity of
      thioglycollate-stimulated animals, though this effect was not statistically
      significant. CONCLUSION: This is the first set of studies that reports the novel
      anti-inflammatory effects of doxazosin.

PMID- 23146879
TI  - Prognostic value of electrographic postanoxic status epilepticus in comatose
      cardiac-arrest survivors in the therapeutic hypothermia era.
AB  - BACKGROUND: The independent prognostic significance of postanoxic status
      epilepticus (PSE) has not been evaluated prospectively since the introduction of
      therapeutic hypothermia. We studied 1-year functional outcomes and their
      determinants in comatose survivors of cardiac arrest (CA), with special attention
      to PSE. METHODS: 106 comatose CA survivors admitted to the intensive care unit in
      2005-2010 were included in a prospective observational study. The main outcome
      measure was a Cerebral Performance Category scale (CPC) of 1 or 2 (favorable
      outcome) 1 year after CA. RESULTS: CA occurred out-of-hospital in 89 (84%)
      patients and was witnessed from onset in 94 (89%). Median times were 6 min (IQR,
      0-11) from CA to first-responder arrival and 23 min (14-40) from collapse to
      return of spontaneous circulation. PSE was diagnosed in 33 (31%) patients at a
      median of 39 h (4-49) after CA. PSE was refractory in 24 (22%) cases and
      malignant in 19 (20%). After 1 year, 31 (29.3%) patients had favorable outcomes
      including 2 (6.44%) with PSE. Factors independently associated with poor outcome
      (CPC >= 3) were PSE (odds ratio [OR], 14.28; 95% confidence interval [95% CI],
      2.77-50.0; P=0.001), time to restoration of spontaneous circulation (OR,
      1.04/min; 95% CI, 1-1.07; P=0.035), and LOD score on day 1 (OR, 1.28/point; 95%
      CI, 1.08-1.54; P=0.003). CONCLUSION: PSE strongly and independently predicts a
      poor outcome in comatose CA survivors receiving therapeutic hypothermia, but some
      patients with PSE survive with good functional outcomes. PSE alone is not
      sufficient to predict failure to awaken after CA in the era of therapeutic
      hypothermia.

PMID- 23146880
TI  - Disseminated intravascular coagulation is bad news for patients following cardiac
      arrest.

PMID- 23146881
TI  - Supraglottic airway devices during neonatal resuscitation: an historical
      perspective, systematic review and meta-analysis of available clinical trials.
AB  - INTRODUCTION: Various supraglottic airway devices are routinely used to maintain
      airway patency in children and adults. However, oropharyngeal airways or
      laryngeal masks (LM) are not routinely used during neonatal resuscitation.
      METHODS: The aim of this article was to review the available literature about the
      use of supraglottic airway devices during neonatal resuscitation. We reviewed
      books, resuscitation manuals and articles from 1830 to the present using the
      search terms "Infant", "Newborn", "Delivery Room", "Resuscitation", "Airway
      management", "Positive Pressure Respiration", "Oropharyngeal Airway" and
      "Laryngeal Mask". RESULTS: No study was identified using oropharyngeal airways
      during neonatal resuscitation. Four trials including 509 infants compared
      positive pressure ventilation with a LM, bag and mask or an endotracheal tube.
      Infants in the LM group were intubated less frequently compared to infants in the
      bag and mask ventilation group 4/275 vs. 28/234 (OR 0.13, 95% CI 0.05-0.34).
      Infants resuscitated with the LM had significantly less unsuccessful
      resuscitations 4/275 vs. 31/234 (OR 0.10, 95% CI 0.03-0.28). Two trials including
      34 preterm infants compared surfactant administration via LM vs. endotracheal
      tube. LM surfactant administration was safe and no adverse events were reported.
      CONCLUSION: The efficacy and safety of oropharyngeal airways during neonatal
      resuscitation remain unclear and randomized trials are required. The current
      evidence suggests that resuscitation with a LM is a feasible and safe alternative
      to mask ventilation in infants >34 weeks gestation and birth weight >2000 g.
      However, further randomized control trials are needed to evaluate short- and long
      term outcomes following use of laryngeal masks. In addition, surfactant
      administration via LM should be used only within clinical trials.

PMID- 23146882
TI  - Clinical and functional relevance of melanocortin-4 receptor variants in obese
      German children.
AB  - BACKGROUND: Variants in the melanocortin-4 receptor (MC4R) gene are the most
      frequent cause of monogenic obesity. The relevance of MC4R variations with
      respect to clinical phenotype and biochemical function remains controversial.
      METHODS: We sequenced the MC4R gene in 510 overweight/obese children. The
      clinical phenotype was assessed in a case-control setting matched for age,
      gender, puberty and body mass index. Identified MC4R variants were functionally
      characterized in vitro. RESULTS: The frequency of MC4R variants was 5.3%, with
      functionally relevant mutations (D(90)N, V(103)I/S(127)L, R(165)W, G(181)D)
      occurring in 1.2% (confidence interval 0.26-2.15) of our sample. 4.1% were
      carriers of variants (Y(35)Y, V(103)I, T(112)M, M(200)V, I(251)L) with preserved
      receptor function in vitro. We did not detect large heterozygous deletions by
      multiple-ligand probe amplification assay. There were no differences in
      anthropometric or metabolic parameters between children with loss-of-function
      mutations and noncarriers. Carriers of the V(103)I or I(251)L variant had higher
      high-density lipoprotein cholesterol and HbA1c levels than matched noncarriers of
      MC4R variants. CONCLUSIONS: In our data set of childhood obesity in central
      Germany, we identified functionally relevant mutations in the MC4R gene in only
      1.2% of the children. There were no major significant phenotypic differences
      between obese children with and without MC4R mutations. Hence, the diagnosis of
      genetically caused obesity due to MC4R mutation should be made with caution.

PMID- 23146883
TI  - Exploring our origins--the importance of OriL in mtDNA maintenance and
      replication.

PMID- 23146884
TI  - Reproduction without sex: social and ethical implications.

PMID- 23146886
TI  - Does intelligence require a body? The growing discipline of embodied cognition
      suggests that to understand the world, we must experience the world.

PMID- 23146885
TI  - Phosphatidylinositol 4-kinase IIalpha function at endosomes is regulated by the
      ubiquitin ligase Itch.
AB  - Phosphatidylinositol (PI) 4-phosphate (PI(4)P) and its metabolizing enzymes serve
      important functions in cell signalling and membrane traffic. PI 4-kinase type
      IIalpha (PI4KIIalpha) regulates Wnt signalling, endosomal sorting of signalling
      receptors, and promotes adaptor protein recruitment to endosomes and the trans
      Golgi network. Here we identify the E3 ubiquitin ligase Itch as binding partner
      and regulator of PI4KIIalpha function. Itch directly associates with and
      ubiquitinates PI4KIIalpha, and both proteins colocalize on endosomes containing
      Wnt-activated frizzled 4 (Fz4) receptor. Depletion of PI4KIIalpha or Itch
      regulates Wnt signalling with corresponding changes in Fz4 internalization and
      degradative sorting. These findings unravel a new molecular link between
      phosphoinositide-regulated endosomal membrane traffic, ubiquitin and the
      modulation of Wnt signalling.

PMID- 23146887
TI  - Immunoreceptors: evolution, structure and therapeutic applications.
AB  - The 'Immunoreceptors' meeting took place in July 2012 in beautiful Snowmass
      Village in Colorado, USA. At an altitude of more than two kilometres, researchers
      and clinicians discussed the molecular aspects of immunoreceptors, ranging from B
      and T-cell receptors, to complement and Fc receptors.

PMID- 23146890
TI  - Are viruses our oldest ancestors?

PMID- 23146891
TI  - Life's code script does not code itself. The machine metaphor for living
      organisms is outdated.

PMID- 23146889
TI  - Leptin and insulin pathways in POMC and AgRP neurons that modulate energy balance
      and glucose homeostasis.
AB  - With the steady rise in the prevalence of obesity and its associated diseases,
      research aimed at understanding the mechanisms that regulate and control whole
      body energy homeostasis has gained new interest. Leptin and insulin, two
      anorectic hormones, have key roles in the regulation of body weight and energy
      homeostasis, as highlighted by the fact that several obese patients develop
      resistance to these hormones. Within the brain, the hypothalamic
      proopiomelanocortin and agouti-related protein neurons have been identified as
      major targets of leptin and insulin action. Many studies have attempted to
      discern the individual contributions of various components of the principal
      pathways that mediate the central effects of leptin and insulin. The aim of this
      review is to discuss the latest findings that might shed light on, and lead to a
      better understanding of, energy balance and glucose homeostasis. In addition,
      recently discovered targets and mechanisms that mediate hormonal action in the
      brain are highlighted.

PMID- 23146892
TI  - Reactive oxygen species regulate ERBB2 and ERBB3 expression via miR-199a/125b and
      DNA methylation.
AB  - Overexpression of ERBB2 or ERBB3 is associated with cancer development and poor
      prognosis. In this study, we show that reactive oxygen species (ROS) induce both
      ERBB2 and ERBB3 expression in vitro and in vivo. We also identify that miR-199a
      and miR-125b target ERBB2 and/or ERBB3 in ovarian cancer cells, and demonstrate
      that ROS inhibit miR-199a and miR-125b expression through increasing the promoter
      methylation of the miR-199a and miR-125b genes by DNA methyltransferase 1. These
      findings reveal that ERBB2 and ERBB3 expression is regulated by ROS via miR-199a
      and miR-125b downregulation and DNA hypermethylation.

PMID- 23146894
TI  - Targeting, resolving and quantifying cellular structures by single-molecule
      localization microscopy.
AB  - The second 'Single Molecule Localization Microscopy' symposium was held in August
      2012 at the Ecole Polytechnique Federale de Lausanne in Switzerland. During two
      and a half days, around 100 researchers from across the globe, and in disciplines
      spanning physics, biology, chemistry and computer science, gathered to discuss
      the developments in single-molecule super-resolution imaging and its applications
      to address important biological questions.

PMID- 23146895
TI  - Science and ethics review: the thrill is gone.

PMID- 23146893
TI  - Lamins in development, tissue maintenance and stress.
AB  - Lamins are nuclear intermediate filament proteins. They provide mechanical
      stability, organize chromatin and regulate transcription, replication, nuclear
      assembly and nuclear positioning. Recent studies provide new insights into the
      role of lamins in development, differentiation and tissue response to mechanical,
      reactive oxygen species and thermal stresses. These studies also propose the
      existence of separate filament networks for A- and B-type lamins and identify new
      roles for the different networks. Furthermore, they show changes in lamin
      composition in different cell types, propose explanations for the more than 14
      distinct human diseases caused by lamin A and lamin C mutations and propose a
      role for lamin B1 in these diseases.

PMID- 23146896
TI  - Alternative medicine on trial. Clinical trials home in on complementary therapies
      and complex natural products.

PMID- 23146898
TI  - Challenges in targeting cancer metabolism for cancer therapy.

PMID- 23146897
TI  - Genomic evidence for elevated mutation rates in highly expressed genes.
AB  - Reporter gene assays have demonstrated both transcription-associated mutagenesis
      (TAM) and transcription-coupled repair, but the net impact of transcription on
      mutation rate remains unclear, especially at the genomic scale. Using comparative
      genomics of related species as well as mutation accumulation lines, we show in
      yeast that the rate of point mutation in a gene increases with the expression
      level of the gene. Transcription induces mutagenesis on both DNA strands,
      indicating simultaneous actions of several TAM mechanisms. A significant positive
      correlation is also detected between the human germline mutation rate and
      expression level. These results indicate that transcription is overall mutagenic.

PMID- 23146899
TI  - Characterizing the assembly behaviors of human amylin: a perspective derived from
      C-terminal variants.
AB  - The differences in the C-terminal domains of human amylin peptide variants
      initiate different aggregation processes and differences in the composition of
      the aggregates by affecting the hydrophobic cores, conformations, and intra-sheet
      interactions of the peptides, which have distinct effects on the cytotoxicity of
      the peptides.

PMID- 23146900
TI  - Expression of nogo-a is decreased with increasing gestational age in the human
      fetal brain.
AB  - Nogo is a member of the reticulon family. Our understanding of the physiological
      functions of the Nogo-A protein has grown over the last few years, and this
      molecule is now recognized as one of the most important axonal regrowth
      inhibitors present in central nervous system (CNS) myelin. Nogo-A plays other
      important roles in nervous system development, epilepsy, vascular physiology,
      muscle pathology, stroke, inflammation, and CNS tumors. Since the exact role of
      Nogo-A protein in human brain development is still poorly understood, we studied
      its cellular and regional distribution by immunohistochemistry in the frontal
      lobe of 30 human fetal brains. Nogo-A was expressed in the following cortical
      zones: ependyma, ventricular zone, subventricular zone, intermediate zone,
      subplate, cortical plate, and marginal zone. The number of positive cells
      decreased significantly with increasing gestational age in the subplate and
      marginal zone. Using different antibodies, changes in isoform expression and
      dimerization states could be shown between various cortical zones. The results
      demonstrate a significant change in the expression of Nogo-A during the
      development of the human brain. The effects of its time- and region-specific
      regulation have to be further studied in detail.

PMID- 23146901
TI  - Loss of pRB and p107 disrupts cartilage development and promotes enchondroma
      formation.
AB  - The pocket proteins pRB, p107 and p130 have established roles in regulating the
      cell cycle through the control of E2F activity. The pocket proteins regulate
      differentiation of a number of tissues in both cell cycle-dependent and 
      independent manners. Prior studies showed that mutation of p107 and p130 in the
      mouse leads to defects in cartilage development during endochondral ossification,
      the process by which long bones form. Despite evidence of a role for pRB in
      osteoblast differentiation, it is unknown whether it functions during cartilage
      development. Here, we show that mutation of Rb in the early mesenchyme of p107
      mutant mice results in severe cartilage defects in the growth plates of long
      bones. This is attributable to inappropriate chondrocyte proliferation that
      persists after birth and leads to the formation of enchondromas in the growth
      plates as early as 8 weeks of age. Genetic crosses show that development of these
      tumorigenic lesions is E2f3 dependent. These results reveal an overlapping role
      for pRB and p107 in cartilage development, endochondral ossification and
      enchondroma formation that reflects their coordination of cell-cycle exit at
      appropriate developmental stages. 

PMID- 23146903
TI  - WIP1 phosphatase modulates the Hedgehog signaling by enhancing GLI1 function.
AB  - The Hedgehog-GLI (HH-GLI) signaling plays a critical role in controlling growth
      and tissue patterning during embryogenesis and is implicated in a variety of
      human malignancies, including those of the skin. Phosphorylation events have been
      shown to regulate the activity of the GLI transcription factors, the final
      effectors of the HH-GLI signaling pathway. Here, we show that WIP1 (or PPM1D), an
      oncogenic phosphatase amplified/overexpressed in several types of human cancer,
      is a positive modulator of the HH signaling. Mechanistically, WIP1 enhances the
      function of GLI1 by increasing its transcriptional activity, nuclear localization
      and protein stability, but not of GLI2 nor GLI3. We also find that WIP1 and GLI1
      are in a complex. Modulation of the transcriptional activity of GLI1 by WIP1
      depends on the latter's phosphatase activity and, remarkably, does not require
      p53, a known WIP1 target. Functionally, we find that WIP1 is required for
      melanoma and breast cancer cell proliferation and self-renewal in vitro and
      melanoma xenograft growth induced by activation of the HH signaling.
      Pharmacological blockade of the HH pathway with the SMOOTHENED antagonist
      cyclopamine acts synergistically with inhibition of WIP1 in reducing growth of
      melanoma and breast cancer cells in vitro. Overall, our data uncover a role for
      WIP1 in modulating the activity of GLI1 and in sustaining cancer cell growth and
      cancer stem cell self-renewal induced by activation of the HH pathway. These
      findings open a novel therapeutic approach for human melanomas and, possibly,
      other cancer types expressing WIP1 and with activated HH pathway. 

PMID- 23146902
TI  - NBN phosphorylation regulates the accumulation of MRN and ATM at sites of DNA
      double-strand breaks.
AB  - In response to ionizing radiation, the MRE11/RAD50/NBN complex re-distributes to
      the sites of DNA double-strand breaks (DSBs) where each of its individual
      components is phosphorylated by the serine-threonine kinase, ATM. ATM
      phosphorylation of NBN is required for the activation of the S-phase checkpoint,
      but the mechanism whereby these phosphorylation events signal the checkpoint
      machinery remains unexplained. Here, we describe the use of direct protein
      transduction of the homing endonuclease, I-PpoI, into human cells to generate
      site-specific DSBs. Direct transduction of I-PpoI protein results in rapid
      accumulation and turnover of the endonuclease in live cells, facilitating
      comparisons across multiple cell lines. We demonstrate the utility of this system
      by introducing I-PpoI into isogenic cell lines carrying mutations at the ATM
      phosphorylation sites in NBN and assaying the effects of these mutations on the
      spatial distribution and temporal accumulation of NBN and ATM at DSBs by
      chromatin immunoprecipitation, as well as timing and extent of DSB repair.
      Although the spatial distribution of NBN and ATM recruited to the sites of DSBs
      was comparable between control cells and those expressing phosphorylation mutants
      of NBN, the timing of accumulation of NBN and ATM was altered. Serine-to-alanine
      mutations that blocked phosphorylation resulted in delayed recruitment of both
      NBN and ATM to DSBs. Serine-to-glutamic acid substitutions that mimicked the
      phosphorylation event resulted in both increased and prolonged accumulation of
      both NBN and ATM at DSBs. The repair of DSBs in cells lacking full-length NBN was
      significantly delayed compared with control cells, whereas blocking
      phosphorylation of NBN resulted in a more modest delay in repair. These data
      indicate that following the induction of DSBs, phosphorylation of NBN regulates
      its accumulation, and that of ATM, at sites of DNA DSB as well as the timing of
      the repair of these sites. 

PMID- 23146904
TI  - The CDK1 inhibitory kinase MYT1 in DNA damage checkpoint recovery.
AB  - Inhibition of cyclin-dependent kinase 1 (CDK1) by phosphorylation is a key
      regulatory mechanism for both the unperturbed cell cycle and the DNA damage
      checkpoint. Although both WEE1 and MYT1 can phosphorylate CDK1, little is known
      about the contribution of MYT1. We found that in contrast to WEE1, MYT1 was not
      important for the normal cell cycle or checkpoint activation. Time-lapse
      microscopy indicated that MYT1 did, however, have a rate-determining role during
      checkpoint recovery. Depletion of MYT1 induced precocious mitotic entry when the
      checkpoint was abrogated with inhibitors of either CHK1 or WEE1, indicating that
      MYT1 contributes to checkpoint recovery independently of WEE1. The acceleration
      of checkpoint recovery in MYT1-depleted cells was due to a lowering of threshold
      for CDK1 activation. The kinase activity of MYT1 was high during checkpoint
      activation and reduced during checkpoint recovery. Importantly, although
      depletion of MYT1 alone did not affect long-term cell growth, it potentiated with
      DNA damage to inhibit cell growth in clonogenic survival and tumor xenograft
      models. These results reveal the functions of MYT1 in checkpoint recovery and
      highlight the potential of MYT1 as a target for anti-cancer therapies. 

PMID- 23146905
TI  - BIRC5/Survivin enhances aerobic glycolysis and drug resistance by altered
      regulation of the mitochondrial fusion/fission machinery.
AB  - Gain of chromosome 17q correlates with high-stage disease, an adverse clinical
      outcome and leads to the overexpression of the antiapoptotic protein
      BIRC5/Survivin in neuroblastoma (NB). We have shown before that Survivin defines
      a threshold for the sensitivity of NB cells to DNA-damaging chemotherapeutic
      agents that require FOXO3 activation for apoptosis induction. To investigate the
      molecular basis of apoptosis inhibition we analyzed the function of Survivin at
      mitochondria and uncovered that Survivin induces mitochondrial fragmentation,
      reduces mitochondrial respiration and represses BCL2L11/Bim. Mitochondrial
      fission depends on Survivin-induced recruitment of the fission regulator
      DNM1L/Drp1 to mitochondria. In parallel, Survivin expression inhibits the
      respiratory complex-I, thereby preventing reactive oxygen species accumulation
      and, as a consequence, FOXO3-induced apoptosis. The loss of energy production via
      oxidative phosphorylation is compensated by increased glycolysis in Survivin
      overexpressing NB tumor cells. Glycolysis inhibitors neutralize the antiapoptotic
      effect of Survivin and sensitize high-stage NB to DNA-damaging drugs. This
      suggests that glycolysis inhibitors target an 'archilles heel' of Survivin
      overexpressing NB and may be highly useful as chemosensitizers in the treatment
      of high-stage NB. 

PMID- 23146906
TI  - Flotillin-2 deficiency leads to reduced lung metastases in a mouse breast cancer
      model.
AB  - Flotillin microdomains, specialized lipid raft domains in cell membranes, serve
      as physical platforms for many different molecules important in crucial
      intracellular signaling pathways. Flotillin-2 (Flot2), together with flotillin-1,
      is a marker for lipid raft microdomains distinct from caveolar lipid rafts, and
      has been implicated in the progression of cancer and metastasis formation. Based
      largely on studies in xenograft models, flotillin-2 has been implicated in the
      progression of multiple types of human tumors, including breast cancer. In our
      studies, we identified flotillin-2 as highly amplified in a high-throughput
      comparative genomic hybridization screen of human breast cancer cell lines and
      breast tumor samples. Short hairpin RNA-mediated reduction of flotillin-2 protein
      levels significantly reduced the tumorigenicity and metastatic capability of a
      human breast cancer cell line in vivo. We generated mice deficient for flotillin
      2 and also found a reduction of flotillin-1 protein levels and complete absence
      of flotillin-specific membrane microdomains in these mice. To examine the role of
      Flot2 in mammary tumorigenesis and lung metastasis, we used an in vivo molecular
      genetics approach, crossing a well-characterized transgenic mouse model of breast
      cancer, the MMTV-PyMT (mouse mammary tumor virus-polyoma middle T antigen) mouse,
      with gene-targeted Flot2(-/-) mice. Flotillin-2 deficiency lead to a striking
      reduction in the number of lung metastasis observed, but had no influence on
      primary tumor formation in this model. Our results indicate, using a novel in
      vivo animal model approach, that Flot2 is an important regulator of mammary tumor
      derived lung metastasis.

PMID- 23146908
TI  - Zipper-interacting protein kinase is involved in regulation of ubiquitination of
      the androgen receptor, thereby contributing to dynamic transcription complex
      assembly.
AB  - We have recently identified apoptosis-antagonizing transcription factor (AATF),
      tumor-susceptibility gene 101 (TSG101) and zipper-interacting protein kinase
      (ZIPK) as novel coactivators of the androgen receptor (AR). The mechanisms of
      coactivation remained obscure, however. Here we investigated the interplay and
      interdependence between these coactivators and the AR using the endogenous
      prostate specific antigen (PSA) gene as model for AR-target genes. Chromatin
      immunoprecipitation in combination with siRNA-mediated knockdown revealed that
      recruitment of AATF and ZIPK to the PSA enhancer was dependent on AR, whereas
      recruitment of TSG101 was dependent on AATF. Association of AR and its
      coactivators with the PSA enhancer or promoter occurred in cycles. Dissociation
      of AR-transcription complexes was due to degradation because inhibition of the
      proteasome system by MG132 caused accumulation of AR at enhancer/promoter
      elements. Moreover, inhibition of degradation strongly reduced transcription,
      indicating that continued and efficient transcription is based on initiation,
      degradation and reinitiation cycles. Interestingly, knockdown of ZIPK by siRNA
      had a similar effect as MG132, leading to reduced transcription but enhanced
      accumulation of AR at androgen-response elements. In addition, knockdown of ZIPK,
      as well as overexpression of a dominant-negative ZIPK mutant, diminished
      polyubiquitination of AR. Furthermore, ZIPK cooperated with the E3 ligase Mdm2 in
      AR-dependent transactivation, assembled into a single complex on chromatin and
      phosphorylated Mdm2 in vitro. These results suggest that ZIPK has a crucial role
      in regulation of ubiquitination and degradation of the AR, and hence promoter
      clearance and efficient transcription.

PMID- 23146909
TI  - Post-diphtheritic neuropathy: a clinical study in paediatric intensive care unit
      of a developing country.
AB  - A retrospective study was done on 48 consecutive patients with clinical diagnosis
      of post-diphtheritic neuropathy admitted to the paediatric intensive care unit of
      tertiary care hospital in North India between January 2008 and December 2010 to
      study the clinical profile of post-diphtheritic neuropathy in children. The case
      records were reviewed and information regarding personal details, clinical
      features, recovery parameters and outcome was recorded using a predesigned
      proforma. Median age was 4.25 years. All cases were unimmunized. Median latency
      period was 15 days. Of the children, 52% had palatal palsy whereas 48% had limb
      weakness initially. Median duration of progression of weakness was five days.
      Limb muscle weakness was present in 94%. Respiratory muscles were involved in
      85.4% cases and 60.4% required mechanical ventilation, while 14.6% had fatal
      outcome and 10.4% had hypoxic neurological injury. Boys were affected more.
      Median duration of latency was shorter; muscle weakness, progression and recovery
      were faster as compared with observational studies in adults.

PMID- 23146907
TI  - Ableson kinases negatively regulate invadopodia function and invasion in head and
      neck squamous cell carcinoma by inhibiting an HB-EGF autocrine loop.
AB  - Head and neck squamous cell carcinoma (HNSCC) has a proclivity for locoregional
      invasion. HNSCC mediates invasion in part through invadopodia-based proteolysis
      of the extracellular matrix (ECM). Activation of Src, Erk1/2, Abl and Arg
      downstream of epidermal growth factor receptor (EGFR) modulates invadopodia
      activity through phosphorylation of the actin regulatory protein cortactin. In
      MDA-MB-231 breast cancer cells, Abl and Arg function downstream of Src to
      phosphorylate cortactin, promoting invadopodia ECM degradation activity and thus
      assigning a pro-invasive role for Ableson kinases. We report that Abl kinases
      have an opposite, negative regulatory role in HNSCC where they suppress
      invadopodia and tumor invasion. Impairment of Abl expression or Abl kinase
      activity with imatinib mesylate enhanced HNSCC matrix degradation and 3D collagen
      invasion, functions that were impaired in MDA-MB-231. HNSCC lines with elevated
      EGFR and Src activation did not contain increased Abl or Arg kinase activity,
      suggesting that Src could bypass Abl/Arg to phosphorylate cortactin and promote
      invadopodia ECM degradation. Src-transformed Abl(-/-)/Arg(-/-) fibroblasts
      produced ECM degrading invadopodia containing pY421 cortactin, indicating that
      Abl/Arg are dispensable for invadopodia function in this system. Imatinib-treated
      HNSCC cells had increased EGFR, Erk1/2 and Src activation, enhancing cortactin
      pY421 and pS405/418 required for invadopodia function. Imatinib stimulated
      shedding of the EGFR ligand heparin-binding EGF-like growth factor (HB-EGF) from
      HNSCC cells, where soluble HB-EGF enhanced invadopodia ECM degradation in HNSCC
      but not in MDA-MB-231. HNSCC cells treated with inhibitors of the EGFR
      invadopodia pathway indicated that EGFR and Src are required for invadopodia
      function. Collectively, our results indicate that Abl kinases negatively regulate
      HNSCC invasive processes through suppression of an HB-EGF autocrine loop
      responsible for activating a EGFR-Src-cortactin cascade, in contrast to the
      invasion promoting functions of Abl kinases in breast and other cancer types. Our
      results provide mechanistic support for recent failed HNSCC clinical trials
      utilizing imatinib. 

PMID- 23146911
TI  - A coherent RC circuit.
AB  - We review the first experiment on dynamic transport in a phase-coherent quantum
      conductor. In our discussion, we highlight the use of time-dependent transport as
      a means of gaining insight into charge relaxation on a mesoscopic scale. For this
      purpose, we studied the ac conductance of a model quantum conductor, i.e. the
      quantum RC circuit. Prior to our experimental work, Buttiker et al (1993 Phys.
      Lett. A 180 364-9) first worked on dynamic mesoscopic transport in the 1990s.
      They predicted that the mesoscopic RC circuit can be described by a quantum
      capacitance related to the density of states in the capacitor and a constant
      charge-relaxation resistance equal to half of the resistance quantum h/2e(2),
      when a single mode is transmitted between the capacitance and a reservoir. By
      applying a microwave excitation to a gate located on top of a coherent
      submicronic quantum dot that is coupled to a reservoir, we validate this
      theoretical prediction on the ac conductance of the quantum RC circuit. Our study
      demonstrates that the ac conductance is directly related to the dwell time of
      electrons in the capacitor. Thereby, we observed a counterintuitive behavior of a
      quantum origin: as the transmission of the single conducting mode decreases, the
      resistance of the quantum RC circuit remains constant while the capacitance
      oscillates.

PMID- 23146910
TI  - Effect of a novel 17,20-lyase inhibitor, orteronel (TAK-700), on androgen
      synthesis in male rats.
AB  - Endogenous androgens play a role in the development and progression of prostate
      cancer (PC), thus androgen suppression may offer an effective therapeutic
      strategy for this disease. Orteronel (TAK-700), 6-[(7S)-7-hydroxy-6,7-dihydro-5H
      pyrrolo[1,2-c]imidazol-7-yl]-N-methyl-2-naphthamide, is a novel, non-steroidal,
      selective inhibitor of the 17,20-lyase activity of CYP17A--a key enzyme in the
      production of steroidal hormones--and is being developed as a therapy for PC. The
      purpose of this study was to elucidate the inhibitory activity of orteronel, in
      particular its specificity for androgen synthesis enzymes, in male rats--an
      androgen-synthesis model that largely reflects this pathway in humans. Orteronel
      inhibited 17,20-lyase activity in rats with an IC(50) of 1200 nM but did not
      inhibit 17alpha-hydroxylase or 11beta-hydroxylase (CYP11B1) activity in rats at
      concentrations up to 10 MUM. In cellular steroidogenesis assays using rat
      testicular cells, orteronel suppressed testosterone and androstenedione
      production with an IC(50) of 640 nM and 210 nM, respectively, but did not
      suppress either corticosterone or aldosterone production in rat adrenal cells at
      concentrations up to 30 MUM. In addition, serum testosterone and androstenedione
      levels in human chorionic gonadotropin-injected hypophysectomized rats were
      significantly reduced by single oral administration of orteronel at a dose of 30
      mg/kg (both p <= 0.01); serum corticosterone and aldosterone levels in ACTH
      injected hypophysectomized rats did not result in significant differences
      compared with controls, following orteronel administration at doses up to 300
      mg/kg. Serum testosterone levels in intact male rats were significantly reduced
      by orteronel 4h after dosing at 100mg/kg (p <= 0.01); testosterone levels showed
      a tendency to recover afterward. In intact male rats, the weight of the prostate
      glands and seminal vesicles was decreased in a dose-dependent manner following
      multiple doses of orteronel at 37.5, 150, and 600 mg/kg, TID for 4 days. The
      reversibility of orteronel was further confirmed using a human adrenocortical
      tumor cell line. In summary, orteronel is a selective and reversible 17,20-lyase
      inhibitor, and decreases the weight of androgen-dependent organs in male rats.
      Our data suggests that orteronel would therefore be effective for androgen
      dependent disorders such as PC.

PMID- 23146913
TI  - Catalytic enantioselective addition of terminal 1,3-diynes to N-sulfonyl
      aldimines: access to chiral diynylated carbinamines.
AB  - An efficient method for the asymmetric synthesis of chiral diynylated
      carbinamines is described. The direct catalytic enantioselective addition of
      terminal 1,3-diynes to N-sulfonyl aldimines proceeded smoothly under mild
      reaction conditions to produce diynylated carbinamines in up to 98% yield and 99%
      ee.

PMID- 23146912
TI  - Near-infrared spectroscopy can predict the onset of cerebral hyperperfusion
      syndrome after carotid endarterectomy.
AB  - BACKGROUND: Cerebral hyperperfusion syndrome (CHS) after carotid endarterectomy
      (CEA) is a potential life-threatening complication. Therefore, early
      identification and treatment of patients at risk is essential. CHS can be
      predicted by a doubling of postoperative transcranial Doppler (TCD)-derived mean
      middle cerebral artery blood velocity (V(mean)) compared to preoperative values.
      However, in approximately 15% of CEA patients, an adequate TCD signal cannot be
      obtained due to an insufficient temporal bone window. Moreover, the use of TCD
      requires specifically skilled personnel. An alternative and promising technique
      of noninvasive cerebral monitoring is relative frontal lobe oxygenation (rSO(2))
      measured by near-infrared spectroscopy (NIRS), which offers on-line information
      about cerebral oxygenation without the need for specialized personnel. In this
      study, we assess whether NIRS and perioperative TCD are related to the onset CHS
      following CEA. METHODS: Patients who underwent CEA under general anesthesia and
      had a sufficient TCD window were prospectively included. The V(mean) and rSO(2)
      measured before induction of anesthesia were compared to measurements performed
      in the first postoperative hour (DeltaV(mean), DeltarSO(2), respectively).
      Logistic regression analysis was performed to determine the relationship between
      DeltaV and DeltarSO(2) and the occurrence of CHS. Subsequently, receiver
      operating characteristic (ROC) curve analysis was used to determine the optimal
      cutoff values. Diagnostic values were shown as positive and negative predictive
      values (PPV and NPV). RESULTS: In total, 151 patients were included, of which 7
      patients developed CHS. The DeltaV(mean) and DeltarSO(2) differed between CHS and
      non-CHS patients (median, interquartile range), i.e. 74% (67-103) versus 16% (-2
      to 41), p = 0.001, and 7% (4-15) versus 1% (-6 to 7), p = 0.009, respectively.
      The mean arterial blood pressure did not change. Postoperative DeltaV(mean) and
      DeltarSO(2) were significantly related to the occurrence of CHS [odds ratio (OR)
      1.40 (95% CI 1.02-1.93) per 30% increase in V(mean) and OR 1.82 (95% CI 1.11
      2.99) per 5% increase in rSO(2)]. ROC curve analysis showed an area under the
      curve of 0.88 (p = 0.001) for DeltaV(mean) and an optimal cutoff value of 67%
      increase (PPV 38% and NPV 99%), and an area under the curve of 0.79 (p = 0.009)
      for DeltarSO(2) and an optimal cutoff value of 3% rSO(2) increase (PPV 11% and
      NPV 100%). The combination of both monitoring techniques provided a PPV of 58%
      and an NPV of 99%. CONCLUSIONS: Both TCD and NIRS measurements can be used to
      safely identify patients not at risk of developing CHS. It appears that NIRS is a
      good alternative when a TCD signal cannot be obtained.

PMID- 23146915
TI  - Dynamic magnetic MOFs.
AB  - In this review we combine the use of coordination chemistry with the concepts of
      molecular magnetism to design magnetic Metal-Organic Frameworks (MOFs) in which
      the crystalline network undergoes a dynamic change upon application of an
      external stimulus. The various approaches so far developed to prepare these kinds
      of chemically or physically responsive MOFs with tunable magnetic properties are
      presented.

PMID- 23146914
TI  - Accelerated large volume irradiation with dynamic Jaw/Dynamic Couch Helical
      Tomotherapy.
AB  - BACKGROUND: Helical Tomotherapy (HT) has unique capacities for the radiotherapy
      of large and complicated target volumes. Next generation Dynamic Jaw/Dynamic
      Couch HT delivery promises faster treatments and reduced exposure of organs at
      risk due to a reduced dose penumbra. METHODS: Three challenging clinical
      situations were chosen for comparison between Regular HT delivery with a field
      width of 2.5 cm (Reg 2.5) and 5.0 cm (Reg 5.0) and DJDC delivery with a maximum
      field width of 5.0 cm (DJDC 5.0): Hemithoracic Irradiation, Whole Abdominal
      Irradiation (WAI) and Total Marrow Irradiation (TMI). For each setting, five CT
      data sets were chosen, and target coverage, conformity, integral dose, dose
      exposure of organs at risk (OAR) and treatment time were calculated. RESULTS:
      Both Reg 5.0 and DJDC 5.0 achieved a substantial reduction in treatment time
      while maintaining similar dose coverage. Treatment time could be reduced from
      10:57 min to 3:42 min / 5:10 min (Reg 5.0 / DJDC 5.0) for Hemithoracic
      Irradiation, from 18:03 min to 8:02 min / 8:03 min for WAI and to 18:25 min /
      18:03 min for TMI. In Hemithoracic Irradiation, OAR exposure was identical in all
      modalities. For WAI, Reg 2.5 resulted in lower exposure of liver and bone. DJDC
      plans showed a small but significant increase of ~ 1 Gy to the kidneys, the
      parotid glans and the thyroid gland. While Reg 5.0 and DJDC were identical in
      terms of OAR exposure, integral dose was substantially lower with DJDC, caused by
      a smaller dose penumbra. CONCLUSIONS: Although not clinically available yet, next
      generation DJDC HT technique is efficient in improving the treatment time while
      maintaining comparable plan quality.

PMID- 23146916
TI  - Effects of vigorous mixing of blood vacuum tubes on laboratory test results.
AB  - OBJECTIVE: To evaluate the effect of tubes mixing (gentle vs. vigorous) on
      diagnostic blood specimens collected in vacuum tube systems by venipuncture.
      DESIGN AND METHODS: Blood was collected for routine coagulation, immunochemistry
      and hematological testing from one hundred volunteers into six vacuum tubes: two
      3.6 mL vacuum tubes containing 0.4 mL of buffered sodium citrate (9NC) 0.109
      mol/L: 3.2 W/V%; two 3.5 mL vacuum tubes with clot activator and gel separator;
      and two 3.0 mL vacuum tubes containing 5.9 mg K(2)EDTA (Terumo Europe, Belgium).
      Immediately after the venipuncture all vacuum tubes (each of one additive type)
      were processed through two different procedures: i) Standard: blood specimens in
      K(2)EDTA- or sodium citrate-vacuum tubes were gently inverted five times whereas
      the specimens in tubes with clot activator and gel separator were gently inverted
      ten times, as recommended by the manufacturer; ii) Vigorous mix: all blood
      specimens were shaken up vigorously during 3-5s independently of the additive
      type inside the tubes. The significance of the differences between samples was
      assessed by Student's t-test or Wilcoxon ranked-pairs test after checking for
      normality. The level of statistical significance was set at P<0.05. RESULTS: No
      significant difference (P<0.05) was detected between the procedures for all
      tested parameters. Surprisingly only a visual alteration (presence of foam on the
      top) was shown by all the tubes mixed vigorously before centrifugation (Fig. 1 A,
      B and C). Moreover the serum tubes from vigorous mixing procedure shows a "blood
      ring" on the tube top after stopper removal (Fig. 1 D). CONCLUSION: Our results
      drop out a paradigm suggesting that the incorrect primary blood tubes mixing
      promotes laboratory variability. We suggest that similar evaluation should be
      done using other brands of vacuum tubes by each laboratory manager.

PMID- 23146917
TI  - Proteomic analysis of the cilia membrane of Paramecium tetraurelia.
AB  - Channels, pumps, receptors, cyclases and other membrane proteins modulate the
      motility and sensory function of cilia, but these proteins are generally under
      represented in proteomic analyses of cilia. Studies of these ciliary membrane
      proteins would benefit from a protocol to greatly enrich for integral and
      lipidated membrane proteins. We used LC-MS/MS to compare the proteomes of
      unfractionated cilia (C), the ciliary membrane (CM) and the ciliary membrane in
      the detergent phase (DP) of Triton X-114 phase separation. 55% of the proteins in
      DP were membrane proteins (i.e. predicted transmembrane or membrane-associated
      through lipid modifications) and 31% were transmembrane. This is to be compared
      to 23% membrane proteins with 9% transmembrane in CM and 9% membrane proteins
      with 3% transmembrane in C. 78% of the transmembrane proteins in the DP were
      found uniquely in DP, and not in C or CM. There were ion channels, cyclases,
      plasma membrane pumps, Ca(2+) dependent protein kinases, and Rab GTPases involved
      in the signal transduction in DP that were not identified in the other C and CM
      preparations. Of 267 proteins unique to the DP, 147 were novel, i.e. not found in
      other proteomic and genomic studies of cilia.

PMID- 23146918
TI  - Islet autotransplantation to preserve beta cell mass in selected patients with
      chronic pancreatitis and diabetes mellitus undergoing total pancreatectomy.
AB  - OBJECTIVES: Islet autotransplantation (IAT) is performed in nondiabetic patients
      with chronic pancreatitis at the time of total pancreatectomy (TP) to minimize
      risk of postoperative diabetes. The role of TP-IAT in patients with chronic
      pancreatitis and C-peptide-positive diabetes is not established. We postulate
      that IAT can preserve beta cell mass and thereby benefit patients with
      preexisting diabetes undergoing TP. METHODS: Preoperative metabolic testing,
      islet isolation outcomes, and subsequent islet graft function were reviewed for
      27 patients with diabetes mellitus and chronic pancreatitis undergoing TP-IAT.
      The relationships between the results of preoperative metabolic testing and islet
      isolation outcomes were explored using regression analysis. RESULTS: Mean islet
      yield was 2060 (SD, 2408) islet equivalents/kg. Peak C-peptide (from mixed meal
      tolerance testing) was the strongest predictor of islet yield, with higher
      stimulated C-peptide levels associated with greater islet mass. Half of the
      patients who had C-peptide levels measured after transplantation demonstrated C
      peptide production at a level that conveys protective benefit in type 1 diabetes
      (>= 0.6 ng/mL). CONCLUSIONS: These findings provide proof of concept that
      significant islet mass can be isolated in patients with chronic pancreatitis and
      C-peptide-positive diabetes mellitus undergoing TP-IAT. Stimulated C-peptide may
      be a useful marker of islet mass before transplantation in these patients.

PMID- 23146919
TI  - Triptolide ameliorates autoimmune diabetes and prolongs islet graft survival in
      nonobese diabetic mice.
AB  - OBJECTIVES: Triptolide (TPL) possesses profound immunosuppressive effects and has
      potential in allograft transplantation. We investigated whether TPL treatment
      prevents autoimmune diabetes in nonobese diabetic (NOD) mice and prolongs the
      survival of islet grafts against autoimmune attack or allograft rejection.
      METHODS: Diabetic incidence was monitored in TPL-treated NOD mice. Nonobese
      diabetic or BALB/c islets were transplanted into diabetic recipients treated with
      TPL. Different T-cell subsets in grafts or spleen were analyzed. The
      proliferation, apoptosis, cytokines, and activities of AKT, NFkappaB, and
      caspases 3, 8, and 9 of T cells were determined. RESULTS: Diabetic incidence was
      reduced and inflammatory cytokines were decreased in islets and spleen under TPL
      treatment. T-cell proliferation was reduced and the survival of syngeneic or
      allogeneic grafts was significantly increased in TPL-treated mice. The
      populations of CD4, CD8, CD4CD69, CD8CD69, and interferon-gamma-producing T cells
      in islet grafts and spleen were reduced. Triptolide treatment increased the
      apoptosis of T cells in the spleen of recipients. Levels of phosphorylated
      protein kinase B and phosphorylated inhibitor of kappa B in splenocytes were
      reduced and caspases 3, 8, and 9 were increased in TPL-treated mice. CONCLUSIONS:
      Triptolide treatment not only reduced the diabetic incidence in NOD mice but also
      prolonged the survival of syngeneic or allogeneic grafts.

PMID- 23146920
TI  - Evaluation of SOX9 expression in pancreatic ductal adenocarcinoma and intraductal
      papillary mucinous neoplasm.
AB  - OBJECTIVES: Sex-determining region Y (SRY) box 9 (SOX9) is an important
      transcription factor required for development and has been implicated in several
      types of cancer. Sex-determining region Y box 9 has never been linked to
      pancreatic ductal adenocarcinoma (PDAC) and intraductal papillary mucinous
      neoplasm (IPMN) of the pancreas. The aim of this study was to investigate the
      relationship between SOX9 and PDAC and that between SOX9 and IPMN. METHODS:
      Surgical specimens were obtained from 55 patients with PDAC and 68 patients with
      IPMN and were investigated using SOX9 immunohistochemical analysis. RESULTS: The
      rate of SOX9 positive cells to total pancreatic duct epithelial cells in a normal
      pancreas was 82.7%. On the other hand, the SOX9 positive rate in PDAC was 0.8%.
      There was a significant difference between the normal pancreas and PDAC (P =
      0.0002). In IPMN, the SOX9 positive rate gradually decreased according to tumor
      progression, with the following rates observed: intraductal papillary mucinous
      adenoma (66.3%); noninvasive intraductal papillary mucinous carcinoma (46.3%);
      minimally invasive intraductal papillary mucinous carcinoma (30.5%); and invasive
      carcinoma originating in intraductal papillary mucinous carcinoma (2.3%). There
      were significant differences between each group (P < 0.05). CONCLUSIONS: Our data
      suggested that SOX9 might contribute to carcinogenesis in PDAC and IPMN.

PMID- 23146922
TI  - Clinicopathologic features and outcomes of pancreatic cysts during a 12-year
      period.
AB  - OBJECTIVE: Pancreatic cysts are being detected more frequently with advances in
      abdominal imaging. We designed this study to identify the characteristics of
      pancreatic cysts upon long-term follow-up and to define the proper management of
      them. METHODS: We identified 1386 patients diagnosed with pancreatic cysts at our
      hospital from 1999 to 2010 and analyzed clinicopathologic data including
      radiological findings. RESULTS: At initial diagnosis, 515 patients (37.2%) were
      classified as being at high-risk for malignancy, and 247 patients (17.8%)
      underwent surgery identifying 128 borderline or malignant cysts (51.8%).
      Borderline or malignant cysts were associated with older age, male sex, elevated
      serum level of lipase, carcinoembryonic antigen (CEA) or carbohydrate antigen 19
      9 (CA 19-9), and a dilated pancreatic duct. Long-term follow-up for at least 24
      months revealed that most of cystic lesions unchanged in size but malignant
      transformation was observed in 7 patients. CONCLUSIONS: Most lesions with low or
      indeterminate risk did not changed in size during follow-up period, but one fifth
      of high-risk lesions were identified as borderline or malignant after surgery.
      Surgical resection should be performed in patients with high-risk cysts
      considering their clinical condition, and radiological follow-up of nonsurgically
      managed cysts should be continued for more than 6 years.

PMID- 23146921
TI  - Neutrophil gelatinase-associated lipocalin, macrophage inhibitory cytokine 1, and
      carbohydrate antigen 19-9 in pancreatic juice: pathobiologic implications in
      diagnosing benign and malignant disease of the pancreas.
AB  - OBJECTIVE: Pancreatic diseases pose significant diagnostic challenge as signs and
      symptoms often overlap. We investigated the potential of pancreatic juice
      neutrophil gelatinase-associated lipocalin, macrophage inhibitory cytokine 1 (MIC
      1), and carbohydrate antigen 19-9 (CA19-9) to aid in the diagnosis of patients
      with symptoms suggestive of pancreatic diseases. METHODS: A total of 105 chronic
      pancreatitis (CP), pancreatic cancer (PC), and nonpancreatic nonhealthy (patients
      with symptoms mimicking pancreatic disease but found to be free of any pancreatic
      disease) patients underwent endoscopic pancreatic juice collection after secretin
      stimulation. Neutrophil gelatinase-associated lipocalin and MIC-1 levels were
      measured by enzyme-linked immunosorbent assay, whereas CA19-9 was measured by
      radioimmunoassay. RESULTS: Neutrophil gelatinase-associated lipocalin, MIC-1, and
      CA19-9 were significantly elevated in the pancreatic juice of patients with CP
      and patients with PC as compared with nonpancreatic nonhealthy controls (P <=
      0.034). Neutrophil gelatinase-associated lipocalin seemed most promising in
      differentiating diseased versus nondiseased pancreata (areas under the curve,
      0.88-0.91), whereas MIC-1 was found to be higher in patients with PC than in
      patients with CP (P = 0.043). Interestingly, MIC-1 levels in diabetic patients
      with PC were higher than in nondiabetic patients with PC (P = 0.030) and diabetic
      patients with CP (P = 0.087). Carbohydrate antigen 19-9 showed the least ability
      to distinguish patient groups (areas under the curve, 0.61-0.76). CONCLUSIONS:
      Pancreatic juice neutrophil gelatinase-associated lipocalin shows potential
      utility in establishing pancreatic etiology in the context of nonspecific
      symptoms, whereas MIC-1 may aid in differentiating PC from CP.

PMID- 23146923
TI  - High alcohol consumption increases the risk of pancreatic stone formation and
      pancreatic atrophy in autoimmune pancreatitis.
AB  - OBJECTIVES: This study aimed to investigate risk factors for pancreatic stones
      and atrophy in autoimmune pancreatitis (AIP). METHODS: Seventy-one patients with
      AIP observed for more than 1 year were enrolled. The frequency of pancreatic
      stone development and atrophy on computed tomography as well as their risk
      factors were examined. RESULTS: Pancreatic stones and atrophy were observed in 13
      and 43 patients, respectively. Alcohol consumption of greater than 50 g/d was the
      only significant risk factor for pancreatic atrophy in univariate analysis.
      Alcohol intake of greater than 50 g/d was observed in 6 of 13 patients with
      stones and 10 of 58 patients without stones (46% vs 17%, P = 0.059). Alcohol
      intake of greater than 50 g/d was observed in 14 of 43 patients with atrophy and
      2 of 28 patients without atrophy (33% vs 7.1%, P = 0.018). In multivariate
      analysis, alcohol consumption was a significant risk factor both for pancreatic
      stone formation (odds ratio [OR], 7.47; P = 0.040) and atrophy (OR 6.24; P =
      0.034). Higher age at onset was another significant risk factor for pancreatic
      atrophy (OR 1.07 per year; P = 0.029). CONCLUSIONS: Alcohol consumption of
      greater than 50 g/d increases the risk of pancreatic stone development and
      atrophy in patients with AIP.

PMID- 23146924
TI  - Endoscopic ultrasound-guided biopsy of pancreatic metastases: a large single
      center experience.
AB  - OBJECTIVES: This study aimed to describe a single-center experience with
      endoscopic ultrasound (EUS) features as well as the diagnostic role and clinical
      impact of EUS-guided fine-needle aspiration (EUS-FNA) and Trucut biopsy (EUS-TCB)
      in patients with pancreatic metastases. METHODS: Demographic, clinical, EUS,
      pathological, clinical outcome, and follow-up data of patients who underwent EUS
      at our institution between October 1998 and March 2010 for a known or suspected
      pancreatic metastasis were abstracted. RESULTS: Forty-nine patients (23 males;
      median age, 63 years; range 30-83 years) with 72 pancreatic masses were
      identified. Primary tumor sites included kidney (21), lung (8), skin (6), colon
      (4), breast (3), small bowel (2), stomach (2), liver (1), ovary (1), and bladder
      (1). Of the 72 pancreatic lesions, EUS-FNA of 49 was performed (median, 4.1
      passes; range, 2-9 passes) without complications. An EUS-TCB after EUS-FNA was
      performed in 2 patients and confirmed renal cell carcinoma in one and was
      nondiagnostic in one. The EUS-FNA provided the first diagnosis of "recurrent
      malignancy" in all the 44 patients at a median time of 65 months (range, 1-348
      months) after diagnosis of the primary tumor. CONCLUSIONS: Endoscopic ultrasound
      FNA and EUS-TCB may assist with the cytological diagnosis of pancreatic
      metastases and may have a major clinical impact.

PMID- 23146925
TI  - NOXious signaling in pain processing.
AB  - Chronic pain affects millions of people and often causes major health problems.
      Accumulating evidence indicates that the production of reactive oxygen species
      (ROS), such as superoxide anion or hydrogen peroxide, is increased in the
      nociceptive system during chronic inflammatory and neuropathic pain, and that ROS
      can act as specific signaling molecules in pain processing. Reduction of ROS
      levels by administration of scavengers or antioxidant compounds attenuated the
      nociceptive behavior in various animal models of chronic pain. However, the
      sources of increased ROS production during chronic pain and the role of ROS in
      pain processing are poorly understood. Current work revealed pain-relevant
      functions of the Nox family of NADPH oxidases, a group of electron-transporting
      transmembrane enzymes whose sole function seems to be the generation of ROS. In
      particular, significant expression of the Nox family members Nox1, Nox2, and Nox4
      in various cells of the nociceptive system has been discovered. Studies using
      knockout mice suggest that these Nox enzymes specifically contribute to distinct
      signaling pathways in chronic inflammatory and/or neuropathic pain states.
      Accordingly, targeting Nox1, Nox2, and Nox4 could be a novel strategy for the
      treatment of chronic pain. Currently selective inhibitors of Nox enzymes are
      being developed. Here, we introduce the distinct roles of Nox enzymes in pain
      processing, we summarize recent findings in the understanding of ROS-dependent
      signaling pathways in the nociceptive system, and we discuss potential analgesic
      properties of currently available Nox inhibitors.

PMID- 23146926
TI  - Ivabradine improves all aspects of quality of life assessed with the 36-item
      short form health survey in subjects with chronic ischemic heart disease compared
      with beta-blockers.
AB  - No published studies have evaluated quality of life (QOL) with the 36-item Short
      Form Health Survey (SF-36) in subjects with chronic stable angina pectoris
      (CSAP). We evaluated whether a 1-month treatment with 10 mg ivabradine (IVA) or
      beta-blockers (bisoprolol 2.5 mg/day, carvedilol 12.5 mg/day, atenolol 50 mg/day)
      improves the QOL in patients with CSAP. The SF-36 was administered to 238
      patients randomized in two groups. QOL and heart rate (HR) results after 1 month
      of therapy with IVA and beta-blockers (T1) were compared with basal values (T0).
      Treatments in both groups significantly reduced HR (-11 bpm at T1 compared with
      T0 in the IVA group, -7 bpm at T1 compared with T0 in the beta-blocker group),
      but IVA demonstrated a more significant (p < 0.001) reduction in HR than beta
      blocker treatment (p < 0.01). We observed a significant improvement in all QOL
      dimensions in the group treated with IVA, in particular in the sections regarding
      physical functioning, physical role, and general health (p < 0.001). In the group
      treated with beta-blockers, we found statistically significant improvement only
      in the physical functioning and physical role sections (p < 0.01). With beta
      blocker treatment, many questionnaire sections showed no statistically
      significant improvement (body pain, social functioning, emotional role, and
      mental component summary). IVA treatment significantly improves all aspects of
      QOL in patients with CSAP, unlike beta-blocker treatment. This improvement is
      associated with a greater reduction in HR.

PMID- 23146928
TI  - Rapid image evaluation system for corneal in vivo confocal microscopy.
AB  - PURPOSE: To develop rapid image processing techniques for the objective analysis
      of corneal in vivo confocal micrographs. METHODS: Perpendicular central corneal
      volume scans from healthy volunteers were obtained via laser in vivo confocal
      microscopy. The layer in each volume scan that contained the nerve plexus was
      detected by applying software operators to analyze image features on the basis of
      their size, shape, and contrast. Dendritic immune cells were detected in the
      nerve image on the basis of cellular size, lack of elongation, and brightness
      relative to the nerves. Images that were 20 MUm anterior to the best nerve layer
      images were used for the analysis of epithelial wing cells; wing cell detection
      was based on extended regional minima and a watershed transformation. RESULTS:
      The software successfully detected the best nerve layer images in 15 scans from
      15 eyes. Manual and automatic analyses were 81.8% in agreement for dendritic
      immune cells (for 11 cells in a representative image) and 94.4% in agreement for
      wing cells (for 466 cells in the image). Within 10 seconds per scan, the software
      calculated the number, mean length, and mean density of immune cells; the number,
      mean size, and mean density of wing cells; and the number and mean length of
      nerves. Factors defining the shape and position of cells and nerves also were
      available. CONCLUSIONS: The software rapidly and accurately analyzed the in vivo
      confocal micrographs of the healthy central corneas, yielding quantitative
      results to describe the nerves, dendritic immune cells, and wing cells.

PMID- 23146927
TI  - Rapid detection of Trichinella spiralis larvae in muscles by loop-mediated
      isothermal amplification.
AB  - Trichinella spiralis is a tissue-dwelling nematode parasite. A loop-mediated
      isothermal amplification (LAMP) assay was developed and validated for the
      sensitive and rapid detection of T. spiralis larvae in muscle samples. Sixteen
      sets of primers were designed to recognise distinct sequences of a conserved
      gene, a 1.6kb repetitive element of the Trichinella genome. One set of primers
      was selected as the most appropriate for rapid detection. The specificity and
      sensitivity of the primers in LAMP reactions for T. spiralis larvae and muscle
      samples of mice infected with T. spiralis were determined. Another 10
      heterologous parasites were selected for specificity assays. The results showed
      that target DNA was amplified and visualised by monitoring turbidity and adding
      calcein detection methods within 70min at an isothermal temperature of 63 degrees
      C. The sensitivity of LAMP with the detection limit of 362fg/MUl was >10 times
      higher than that for PCR. The designed primers had a good specificity. No cross
      reactivity was found with the DNA of any other parasites. The assay was able to
      detect T. spiralis in all mouse muscle samples infected with 10 T. spiralis
      larvae on day 20 p.i. We believe this is the first report regarding the
      application of the LAMP assay for detection of T. spiralis larvae in muscle
      samples from experimentally infected mice. This method demonstrates a potentially
      valuable means for the direct detection of T. spiralis larvae in meat inspection.

PMID- 23146929
TI  - Comment on phakic descemet stripping automated endothelial keratoplasty: 
      prevalence and prognostic impact of postoperative cataracts.

PMID- 23146930
TI  - Visante optical coherence tomography and tear function test evaluation of
      cholinergic treatment response in patients with sjogren syndrome.
AB  - PURPOSE: To evaluate tear meniscus changes in patients with Sjogren syndrome (SS)
      receiving oral pilocarpine with Visante optical coherence tomography (OCT).
      METHODS: Eight patients with primary SS were recruited in this prospective
      interventional case series study. Patients received pilocarpine tablets twice a
      day for 3 months. Visual analog scale assessment for dry eye and dry mouth
      symptoms was carried out. Patients underwent OCT and slit-lamp microscopy
      graticule scale tear meniscus height (TMH) measurements, strip meniscometry
      testing, tear film breakup time measurement, fluorescein and Rose Bengal
      staining, and the Schirmer 1 test. The data were analyzed 1 week, 1 month, and 3
      months after treatment. Mann-Whitney test was performed. RESULTS: Visual analog
      scale assessment showed a significant time-wise improvement (P < 0.05). OCT and
      graticule scale TMH measurements significantly improved after 1 week (P < 0.05),
      1 month, and 3 months of treatment (P < 0.001). Strip meniscometry, mean tear
      film stability, and fluorescein and Rose Bengal scores remained improved 3 months
      after treatment (P < 0.001), whereas Schirmer 1 test values tended to improve
      without statistical significance. CONCLUSIONS: Visante OCT was effective in
      monitoring tear meniscus changes during the course of treatment noninvasively and
      quickly. Oral pilocarpine seemed to be effective in improving TMH, and the signs
      and symptoms of dryness in patients with SS.

PMID- 23146931
TI  - Changes in corneal sensation and ocular surface in patients with asymmetrical
      keratoconus.
AB  - PURPOSE: To describe tear function, ocular surface changes, and corneal
      sensitivity in patients with asymmetrical keratoconus (KC). METHODS: Thirty-one
      patients with asymmetrical KC (31 KC and 31 subclinical KC eyes) and 30 control
      subjects (1 eye in each subject) were enrolled in this prospective, case-control
      study. The patients and control subjects underwent ocular surface examinations
      including corneal sensitivity measurements, the Schirmer test using topical
      anesthesia, tear osmolarity test, and conjunctival impression cytology. RESULTS:
      Mean corneal sensitivity and Schirmer test values were significantly lower in the
      KC and subclinical KC eyes compared with the control eyes. The conjunctiva of KC
      and subclinical KC eyes showed significantly higher grades of squamous metaplasia
      and goblet cell loss compared with the control group. However, no significant
      difference in tear osmolarity was found among the groups. CONCLUSIONS: The
      corneal sensitivity and ocular surface changes were significant in the
      subclinical KC and KC eyes compared with the control subjects. Ocular surface
      disease in KC was characterized by tear deficiency disorder and abnormal
      impression cytology results. However, no significant difference in tear
      osmolarity was found among the groups. The decrease in corneal sensitivity and
      ocular surface change may be associated with the pathogenesis of ocular surface
      changes in KC and the progression of the disease.

PMID- 23146933
TI  - The effect of topical infliximab on corneal neovascularization in rabbits.
AB  - PURPOSE: To determine the efficacy of topical application of infliximab [tumor
      necrosis factor-alpha (TNF-alpha) monoclonal antibody] for the treatment of
      corneal neovascularization in the rabbit model. METHODS: In 12 rabbits (24 eyes),
      the corneal stroma was sutured to induce corneal neovascularization. One week
      after suture, corneal neovascularization was confirmed and the subjects were
      divided into 4 groups of 3 rabbits. Sterilized balanced salt solution was applied
      in the control group, and the experimental groups were treated with infliximab
      eye drops of varying concentrations (1, 2, and 4 mg/mL) twice daily for a week.
      The area of corneal neovascularization was measured and analyzed in all groups on
      day 3 and day 7. On day 7, all eyes were extracted to compare the TNF-alpha
      messenger RNA concentration by reverse transcriptase-polymerase chain reaction,
      and the vascular endothelial growth factor activity of corneal neovascular tissue
      was observed by fluorescence immunostaining. RESULT: On day 7, all 3 experimental
      groups (1, 2, and 4 mg/mL) had a significantly reduced area of corneal
      neovascularization compared with the control group (P = 0.043, 0.027, and 0.01,
      respectively) and significantly reduced TNF-alpha messenger RNA (P = 0.038,
      0.031, and 0.022, respectively). Fluorescence immunostaining confirmed the
      reduced expression of vascular endothelial growth factor in all 3 experimental
      groups compared with the control group. CONCLUSIONS: The application of
      infliximab is expected to effectively inhibit corneal neovascularization. Further
      clinical studies are necessary.

PMID- 23146934
TI  - Influence of the precutting and overseas transportation of corneal grafts for
      Descemet stripping automated endothelial keratoplasty on donor endothelial cell
      loss.
AB  - PURPOSE: The authors evaluated the changes in donor endothelial cell density
      (ECD) caused by the precutting and long-distance transportation of corneal grafts
      for Descemet stripping automated endothelial keratoplasty (DSAEK) from overseas
      eye banks. METHODS: A total of 124 consecutive precut donor tissues for DSAEK
      were obtained from overseas eye banks. The ECD was examined before precutting,
      after precutting, and after overseas transportation. Changes in ECD secondary to
      the precutting procedure and after long-distance transportation were evaluated.
      RESULTS: The average ECD before and after precutting was 2637 +/- 336 and 2578 +/
      305, respectively (P = 0.0063). The ECD after overseas transportation was 2468
      +/- 272, which is a significant decrease compared with the ECD after the
      precutting procedure (P < 0.001). The average rate of ECD loss was 1.75% for
      precutting and 3.79% for overseas transportation, with a total ECD loss of 5.68%.
      The ECD before surgery was >2000 cells per square millimeter in all cases, and
      all grafts were available for DSAEK. CONCLUSIONS: Imported precut donor corneas
      form overseas eye banks are a valuable source of donor corneas for DSAEK. The
      cell loss associated with precutting and the overseas transportation of corneal
      grafts on donor endothelial cell loss is acceptable.

PMID- 23146935
TI  - Reply: To PMID 22531433.

PMID- 23146932
TI  - Morphologic alterations of the palpebral conjunctival epithelium in a dry eye
      model.
AB  - PURPOSE: To investigate the normal palpebral conjunctival histology in C57BL/6
      mice and the structural changes that occur in a dry eye model. METHODS: Twenty
      four male and female C57BL/6 mice, 8 untreated and 16 exposed to experimental
      ocular surface desiccating stress (DS). Ocular dryness was induced by
      administration of scopolamine hydrobromide (0.5 mg/0.2 mL) four times a day for 5
      days (DS5) or 10 days (DS10). Counts and measurements were obtained using
      anatomical reference points, and goblet cell density was investigated with a
      variety of stains. RESULTS: Near the junction between the lid margin and the
      normal palpebral conjunctiva, the epithelium had an average thickness of 45.6 +/-
      10.5 MUm, 8.8 +/- 2.0 cell layers, versus 37.7 +/- 5.6 MUm, 7.4 +/- 1.3 layers in
      DS10 (P < 0.05). In the goblet cell-populated palpebral region, the normal
      epithelium was thicker (P < 0.05) than on DS5 and DS10. In the control, 43% of
      the goblet cells were covered by squamous epithelium compared with 58% (DS5) and
      63% (DS10) (P < 0.05). A decreased number of periodic acid-Schiff (PAS)-stained
      goblet cells and Alcian blue-stained goblet cells were observed in the dry eye.
      Not all goblet cells were stained with PAS and Alcian blue. CONCLUSION: The mouse
      palpebral conjunctival epithelium was structurally similar to the human. After
      DS, the palpebral conjunctival epithelium decreased in thickness and goblet cell
      access to the surface seemed to be inhibited by surrounding epithelial cells,
      potentially slowing down their migration to the surface. Differential staining
      with PAS and Alcian blue suggests that there may be different subtypes of
      conjunctival goblet cells.

PMID- 23146936
TI  - Mathematical approximation of Orbscan II central corneal thickness to contact
      ultrasound.
AB  - PURPOSE: To compare Orbscan II central corneal thickness (CCT) measurements
      corrected by five mathematical methods with ultrasound (US) CCT measurements.
      METHODS: The preoperative CCT examinations of the right eyes of 3242 consecutive
      candidates for refractive surgery were retrospectively reviewed. Raw Orbscan data
      were processed by five correction methods: multiplication, subtraction,
      polynomial, logarithmic, and power. For each correction method, the concordance
      between corrected Orbscan and US pachymetries was assessed by mean, Pearson
      correlation, regression analysis, 95% limits of agreement (LoA), and percentage
      of eyes within 8 MUm of US pachymetry. RESULTS: Throughout the 3242 eyes
      analyzed, we found a high Pearson correlation between Orbscan and US measurements
      with all correction methods assessed. The linear multiplication and subtraction
      correction methods brought about mean Orbscan CCT similar to mean US CCT
      measurements. However, they led to relatively high 95% LoA intervals and low
      percentage of eyes within 8 MUm of US pachymetry. In contrast, the three
      nonlinear correction methods proposed herein for the first time narrowed the 95%
      LoA interval (Bland-Altman analysis) together with providing mean Orbscan CCT
      similar to mean US CCT measurements. Moreover, the power fit was the only method
      that was reproducible when extracted from one subset of the cohort and applied in
      another. CONCLUSIONS: Broad 95% LoA intervals were obtained when applying the
      multiplication and the subtraction correction methods, indicating a poor
      agreement between the devices. We suggest the power fit as the default method for
      adjusting Orbscan to US CCT readings.

PMID- 23146939
TI  - Specificity, methodology and psychopathology of emotional attention: an
      introduction to the special issue.

PMID- 23146938
TI  - The gating mechanism of the bacterial mechanosensitive channel MscL revealed by
      molecular dynamics simulations: from tension sensing to channel opening.
AB  - One of the ultimate goals of the study on mechanosensitive (MS) channels is to
      understand the biophysical mechanisms of how the MS channel protein senses forces
      and how the sensed force induces channel gating. The bacterial MS channel MscL is
      an ideal subject to reach this goal owing to its resolved 3D protein structure in
      the closed state on the atomic scale and large amounts of electrophysiological
      data on its gating kinetics. However, the structural basis of the dynamic process
      from the closed to open states in MscL is not fully understood. In this study, we
      performed molecular dynamics (MD) simulations on the initial process of MscL
      opening in response to a tension increase in the lipid bilayer. To identify the
      tension-sensing site(s) in the channel protein, we calculated interaction energy
      between membrane lipids and candidate amino acids (AAs) facing the lipids. We
      found that Phe78 has a conspicuous interaction with the lipids, suggesting that
      Phe78 is the primary tension sensor of MscL. Increased membrane tension by
      membrane stretch dragged radially the inner (TM1) and outer (TM2) helices of MscL
      at Phe78, and the force was transmitted to the pentagon-shaped gate that is
      formed by the crossing of the neighboring TM1 helices in the inner leaflet of the
      bilayer. The radial dragging force induced radial sliding of the crossing
      portions, leading to a gate expansion. Calculated energy for this expansion is
      comparable to an experimentally estimated energy difference between the closed
      and the first subconductance state, suggesting that our model simulates the
      initial step toward the full opening of MscL. The model also successfully
      mimicked the behaviors of a gain of function mutant (G22N) and a loss of function
      mutant (F78N), strongly supporting that our MD model did simulate some essential
      biophysical aspects of the mechano-gating in MscL.

PMID- 23146937
TI  - Touch sense: functional organization and molecular determinants of
      mechanosensitive receptors.
AB  - Cutaneous mechanoreceptors are localized in the various layers of the skin where
      they detect a wide range of mechanical stimuli, including light brush, stretch,
      vibration and noxious pressure. This variety of stimuli is matched by a diverse
      array of specialized mechanoreceptors that respond to cutaneous deformation in a
      specific way and relay these stimuli to higher brain structures. Studies across
      mechanoreceptors and genetically tractable sensory nerve endings are beginning to
      uncover touch sensation mechanisms. Work in this field has provided researchers
      with a more thorough understanding of the circuit organization underlying the
      perception of touch. Novel ion channels have emerged as candidates for
      transduction molecules and properties of mechanically gated currents improved our
      understanding of the mechanisms of adaptation to tactile stimuli. This review
      highlights the progress made in characterizing functional properties of
      mechanoreceptors in hairy and glabrous skin and ion channels that detect
      mechanical inputs and shape mechanoreceptor adaptation.

PMID- 23146940
TI  - Eph/ephrinB signalling is involved in the survival of thymic epithelial cells.
AB  - The signals that determine the survival/death of the thymic epithelial cells
      (TECs) component during embryonic development of the thymus are largely unknown.
      In this study, we combine different in vivo and in vitro experimental approaches
      to define the role played by the tyrosine kinase receptors EphB2 and EphB3 and
      their ligands, ephrinsB, in the survival of embryonic and newborn (NB) TECs. Our
      results conclude that EphB2 and EphB3 are involved in the control of TEC survival
      and that the absence of these molecules causes increased apoptotic TEC
      proportions that result in decreased numbers of thymic cells and a smaller-sized
      gland. Furthermore, in vitro studies using either EphB2-Fc or ephrinB1-Fc fusion
      proteins demonstrate that the blockade of Eph/ephrinB signalling increases TEC
      apoptosis, whereas its activation rescues TECs from cell death. In these assays,
      both heterotypic thymocyte-TEC and homotypic TEC-TEC interactions are important
      for Eph/ephrinB-mediated TEC survival.

PMID- 23146941
TI  - The design and proof of concept for a CD8(+) T cell-based vaccine inducing cross
      subtype protection against influenza A virus.
AB  - In this study, we examined the reactivity of human peripheral blood mononuclear
      cells to a panel of influenza A virus (IAV) CD8(+) T-cell epitopes that are
      recognised by the major human leukocyte antigen (HLA) groups represented in the
      human population. We examined the level of recognition in a sample of the human
      population and the potential coverage that could be achieved if these were
      incorporated into a T-cell epitope-based vaccine. We then designed a candidate
      influenza vaccine that incorporated three of the examined HLA-A2-restricted
      influenza epitopes into Pam2Cys-based lipopeptides. These lipopeptides do not
      require the addition of an adjuvant and can be delivered directly to the
      respiratory mucosa enabling the generation of local memory cell populations that
      are crucial for clearance of influenza. Intranasal administration of a mixture of
      three lipopeptides to HLA-A2 transgenic HHD mice elicited multiple CD8(+) T-cell
      specificities in the spleen and lung that closely mimicked the response generated
      following natural infection with influenza. These CD8(+) T cells were associated
      with viral reduction following H3N1 influenza virus challenge for as long as 3
      months after lipopeptide administration. In addition, lipopeptides containing IAV
      targeting epitopes conferred substantial benefit against death following
      infection with a virulent H1N1 strain. Because CD8(+) T cell epitopes are often
      derived from highly conserved regions of influenza viruses, such vaccines need
      not be reformulated annually and unlike current antibody-inducing vaccines could
      provide cross-protective immunity against newly emerging pandemic viruses.

PMID- 23146942
TI  - Mesenchymal stromal cells and regulatory T cells: the Yin and Yang of peripheral
      tolerance?
AB  - In recent years, mesenchymal stromal cells (MSCs) and regulatory T cells (Tregs)
      have both garnered significant interest from immunologists worldwide, not least
      because of the potential application of both cell types in the treatment of many
      chronic inflammatory and autoimmune diseases. Although both MSCs and Tregs can be
      considered immunosuppressive in their own right, the induction of Tregs by
      activated MSCs is now a well-publicised phenomenon; however, only recently have
      the mechanisms involved in this induction started to become clear. Indeed, it is
      becoming increasingly apparent that there exists a complex interplay between the
      two lineages leading to this potent inhibition of the host immune response. Cell
      contact, soluble mediators-including prostaglandin E(2) and transforming growth
      factor beta-and indirect induction via manipulation of other antigen-presenting
      cells all appear to have vital roles in the interactions between MSCs and Tregs.
      Much still remains to be discovered before we have a full understanding of this
      important aspect of the immune response, but there have already been a multitude
      of clinical trials suggesting that MSC/Treg therapies could offer significant
      benefits in the treatment of both autoimmune disease and graft versus host
      disease. Although these therapies are still in their infancy, the synergy between
      MSCs and Tregs will undoubtedly yield future breakthroughs in the treatment of
      many debilitating conditions and usher in a new wave of targeted, cell-based
      therapeutics.

PMID- 23146943
TI  - Cellular and molecular interactions of mesenchymal stem cells in innate immunity.
AB  - In recent years, human mesenchymal stem/stromal cells (MSC) have attracted major
      attention for their possible clinical applications. In addition to their tissue
      regenerative capacity, they display immune-modulatory properties for which they
      have been used in the treatment of acute graft-versus-host disease and autoimmune
      diseases. Various studies have analyzed the inhibitory effect exerted by MSC on
      cells belonging to acquired or to innate immunity. In this context, MSC have been
      shown to inhibit proliferation and function of natural killer (NK) cells and to
      hinder the generation of dendritic cells and macrophages, thus interfering with
      inflammatory processes and with the generation of type I immune responses. In
      addition, MSC promote the differentiation of regulatory cells and participate in
      the regeneration of tissues damaged as a consequence of the inflammatory process.
      Different molecular mechanisms are involved in the immunosuppressive effect.
      Further investigation on the biology of MSC and on the regulatory events involved
      in their functional activities can help to optimize their use in clinical
      practice.

PMID- 23146944
TI  - Membrane nanotubes in myeloid cells in the adult mouse cornea represent a novel
      mode of immune cell interaction.
AB  - Membrane nanotubes (MNTs) are newly discovered cellular extensions that are
      either blind-ended or can connect widely separated cells. They have predominantly
      been investigated in cultured isolated cells, however, previously we were the
      first group to demonstrate the existence of these structures in vivo in intact
      mammalian tissues. We previously demonstrated the frequency of both cell-cell or
      bridging MNTs and blind-ended MNTs was greatest between major histocompatibility
      complex (MHC) class II(+) cells during corneal injury or TLR ligand-mediated
      inflammation. The present study aimed to further explore the dynamics of MNT
      formation and their size, presence in another tissue, the dura mater, and
      response to stress factors and an active local viral infection of the murine
      cornea. Confocal live cell imaging of myeloid-derived cells in inflamed corneal
      explants from Cx(3)cr1(GFP) and CD11c(eYFP) transgenic mice revealed that MNTs
      form de novo at a rate of 15.5 MUm/min. This observation contrasts with previous
      studies that demonstrated that in vitro these structures originate from cell-cell
      contacts. Conditions that promote formation of MNTs include inflammation in vivo
      and cell stress due to serum starvation ex vivo. Herpes simplex virus-1 infection
      did not cause a significant increase in MNT numbers in myeloid cells in the
      cornea above that observed in injury controls, confirming that corneal epithelium
      injury alone elicits MNT formation in vivo. These novel observations extend the
      currently limited understanding of MNTs in live mammalian tissues.

PMID- 23146947
TI  - Human reproduction program: the first partnership for health and development at
      the WHO.

PMID- 23146948
TI  - WHO reproductive health research at crossroads.

PMID- 23146945
TI  - Delivery of siRNA silencing Runx2 using a multifunctional polymer-lipid
      nanoparticle inhibits osteogenesis in a cell culture model of heterotopic
      ossification.
AB  - Heterotopic ossification (HO) associated with traumatic neurological or
      musculoskeletal injuries remains a major clinical challenge. One approach to
      understanding better and potentially treating this condition is to silence one or
      more genes believed to be responsible for osteogenesis by small interfering RNA
      (siRNA) post-injury. Improved methods of delivering siRNA to myoprogenitor cells
      as well as relevant cell culture models of HO are needed to advance this
      approach. We utilize a model of HO featuring C2C12 myoprogenitor cells stimulated
      to the osteogenic phenotype by addition of BMP-2. For siRNA delivery, we utilize
      a nanocomposite consisting of DOTAP-based cationic liposomes coated with a graft
      copolymer of poly(propylacrylic acid) grafted with polyetheramine (Jeffamine), as
      this system has been shown previously to deliver antisense oligonucleotides
      safely into cells and out of endosomes for gene silencing in vitro and in vivo.
      Delivery of siRNA targeting Runx2, a transcription factor downstream of BMP-2, to
      stimulated C2C12 cells produced greater than 60% down-regulation of the Runx2
      gene. This level of gene silencing was sufficient to inhibit alkaline phosphatase
      activity over the course of several days and calcium phosphate deposition over
      the course of 2 weeks. These results show the utility of the BMP-2/C2C12 model
      for capturing the cellular cell-fate decision in HO. Further, they suggest
      DOTAP/PPAA-g-Jeffamine as a promising delivery system for siRNA-based therapy for
      HO.

PMID- 23146949
TI  - Interview with Prof. Dr. Marleen Temmerman, new director of the WHO Department of
      Reproductive Health and Research, assuming office on October 15, 2012. Interview
      by Thomas M. D'Hooghe.
AB  - In this interview with the editor of Gynecologic and Obstetric Investigation,
      Prof. Dr. Marleen Temmerman, the new director of the WHO Department of
      Reproductive Health and Research (October 15, 2012), presents her vision on the
      role of WHO collaborating centers; the relationship between scientific research,
      guideline development, implementation, and policy; the need to prioritize family
      planning, and the need to improve perinatal and maternal health but also to
      address other global reproductive health problems like infertility, pelvic pain,
      dysfunctional bleeding, and sexually transmitted diseases, which deserve more
      attention from the WHO. She also addresses the challenge to increase funding for
      WHO sexual and reproductive health research.

PMID- 23146950
TI  - The special programme of research in human reproduction: forty years of
      activities to achieve reproductive health for all.
AB  - The Special Programme of Research in Human Reproduction (HRP), co-sponsored by
      the UNDP, UNFPA, WHO, and the World Bank, is celebrating 40 years of activities
      with an expansion of its mandate and new co-sponsors. When it began, in 1972, the
      main focus was on evaluating the acceptability, effectiveness, and safety of
      existing fertility-regulating methods, as well as developing new, improved
      modalities for family planning. In 1994, HRP not only made major contributions to
      the Plan of Action of the International Conference on Population and Development
      (ICPD); it also broadened its scope of work to include other aspects of health
      dealing with sexuality and reproduction, adding a specific perspective on gender
      issues and human rights. In 2002, HRP's mandate was once again broadened to
      include sexually transmitted infections and HIV/AIDS and in 2003 it was further
      expanded to research activities on preventing violence against women and its many
      dire health consequences. Today, the work of the Programme includes research on:
      the sexual and reproductive health of adolescents, women, and men; maternal and
      perinatal health; reproductive tract and sexually transmitted infections
      (including HIV/AIDS); family planning; infertility; unsafe abortion; sexual
      health; screening for cancer of the cervix in developing countries, and gender
      and reproductive rights. Additional activities by the Programme have included:
      fostering international cooperation in the field of human reproduction; the
      elaboration of WHO's first Global Reproductive Health Strategy; work leading to
      the inclusion of ICPD's goal 'reproductive health for all by 2015' into the
      Millennium Development Goal framework; the promotion of critical interagency
      statements on the public health, legal, and human rights implications of female
      genital mutilation and gender-biased sex selection. Finally, HRP has been
      involved in the creation of guidelines and tools, such as the 'Medical
      eligibility criteria for contraceptive use', the 'Global handbook for family
      planning providers', the 'Definition of core competencies in primary health
      care', and designing tools for operationalizing a human rights approach to sexual
      and reproductive health programmes.

PMID- 23146951
TI  - Historical walk: the HRP Special Programme and infertility.
AB  - BACKGROUND/AIMS: The HRP Special Programme (HRP) began addressing 'reproduction'
      problems (infertility) at the same time as 'fertility regulation'
      (contraception). METHODS: This report is based upon data collected from official
      HRP Scientific and Technical Reports. RESULTS: In the 1970s, HRP supported
      research on human and nonhuman primate models to address the basic biology of
      reproduction. Importantly, however, it was the multicountry clinical research
      studies sponsored by HRP during the 1970s and 1980s which led to the
      identification of not only the large burden of disease but also global patterns
      of causation of infertility. The next decade saw the development of WHO
      guidelines and manuals for diagnosis, management, and treatment of infertile
      women and men, with HRP-sponsored operations research focused on adaptation
      within primary health care settings. Consensus consultations held during 2001
      through 2011 resulted in recommendations to stakeholders, as well as the
      identification of barriers and inequities in access to infertility care services.
      CONCLUSION: With renewed focus on infertility through the current development of
      revised guidelines and manuals, and the desire to support critical clinical
      research protocols, including adaptation and implementation research for
      management and monitoring tools being developed through international partners,
      HRP will continue to support future success stories in family, maternal, child,
      and reproductive health.

PMID- 23146953
TI  - Dutch translation of the ICMART-WHO revised glossary on ART terminology.
AB  - BACKGROUND: A standardized set of definitions was needed in the field of
      medically assisted reproduction (MAR) to standardize and harmonize international
      data acquisition and to monitor the availability, efficacy, and safety of
      assisted reproductive technology (ART) worldwide. In order to provide accurate
      national data, the use of a terminology list which was composed and negotiated by
      the International Committee for Monitoring Assisted Reproductive Technology
      (ICMART) is essential, and a translation into Dutch was crucial for its
      implementation in Belgium and the Netherlands. METHOD: The authors of the Dutch
      article translated the English publication that appeared simultaneously in Human
      Reproduction and Fertility and Sterility in 2009. A consensus text was obtained
      after evaluation by experts in the field of MAR both in the Netherlands and in
      Belgium and then by the board of the respective organizations of obstetrics and
      gynecology. It was then sent to the World Health Organization (WHO) for approval
      of publication. RESULT: A translation into Dutch of the ICMART terminology of
      2009 was obtained after consensus was reached on clinical and laboratory
      procedures, outcome variables, and birth. CONCLUSION: The availability and use of
      standardized terminology and its translation into Dutch will add to a more
      standardized communication between professionals responsible for the practice of
      ART and for those responsible for national, regional, and international
      registries.

PMID- 23146952
TI  - Steps through the revision process of reproductive health sections of ICD-11.
AB  - In 2007, the WHO initiated an organizational structure for the 11th revision of
      the International Classification of Diseases (ICD). Effective deployment of ICD
      derived tools facilitates the use and collection of health information in a
      variety of resource settings, promoting quantitatively informed decisions. They
      also facilitate comparison of disease incidence and outcomes between different
      countries and different health care systems around the world. The Department of
      Reproductive Health and Research (RHR) coordinates the revision of chapters 14
      (diseases of the genitourinary system), 15 (pregnancy, childbirth, and
      puerperium), and 16 (conditions originating in the perinatal period). RHR
      convened a technical advisory group (TAG), the Genito-Urinary Reproductive
      Medicine (GURM) TAG, for the ICD revision. The TAG's work reflects the collective
      understanding of sexual and reproductive health and is now available for review
      within the ICD-11 revision process.

PMID- 23146954
TI  - Challenges and implications for biomedical research and intervention studies in
      older populations: insights from the ELDERMET study.
AB  - Older people constitute a growing proportion of the worldwide population. Despite
      this, older people are often excluded from clinical research and are generally
      underrepresented in intervention studies. This severely restricts the ability to
      generalise outcomes from research involving younger populations, which may impact
      on the progression of knowledge and the development of best practice guidelines
      for the care of older people. This opinion piece outlines the challenges and
      practical difficulties experienced and overcome by the ELDERMET project. The
      ELDERMET project has recruited almost 500 subjects, aged 65 years and older,
      across a range of health states from the very frail to the very fit, half of whom
      have been studied at multiple time points. All ELDERMET subjects have
      participated in an extensive protocol and supplied multiple biological sample
      types. The challenges and obstacles faced by both researchers in recruiting older
      subjects and older people engaging with research and intervention studies are set
      out. Strategies are discussed for: the recruitment and retention of older
      subjects; recruiting subjects with physical or cognitive impairment; recruitment
      from specific locations; collecting accurate and robust data, particularly from
      subjects with mild to severe cognitive impairment; intervention product design,
      delivery and compliance. Practical and realistic solutions for maximising the
      engagement of older people with research and intervention studies are offered.
      The increased benefit brought by the generalisation and application of research
      and intervention outcomes to older populations is discussed.

PMID- 23146955
TI  - Chronic nicotine inhibits the therapeutic effects of gemcitabine on pancreatic
      cancer in vitro and in mouse xenografts.
AB  - AIM OF STUDY: Smoking is an established risk factor for pancreatic cancer and
      nicotine replacement therapy (NRT) often accompanies chemotherapy. The current
      study has tested the hypothesis that chronic exposure to low dose nicotine
      reduces the responsiveness of pancreatic cancer to the leading therapeutic for
      this cancer, gemcitabine. METHODS: The effects of chronic nicotine (1 MUm/L) on
      two pancreatic cancer cell lines in vitro and in a xenograft model were assessed
      by immunoassays, Western blots and cell proliferation assays. RESULTS: Exposure
      in vitro to nicotine for 7 days inhibited the gemcitabine-induced reduction in
      viable cells, gemcitabine-induced apoptosis as indicated by reduced expression of
      cleaved caspase-3 while inducing the phosphorylation of signalling proteins
      extracellular signal-regulated kinase (ERK), v-akt thymoma viral oncogene homolog
      (protein kinase B, AKT) and Src. Nicotine (1 MUm/L) in the drinking water for 4
      weeks significantly reduced the therapeutic response of mouse xenografts to
      gemcitabine while reducing the induction of cleaved caspase-3 and the inhibition
      of phosphorylated forms of multiple signalling proteins by gemcitabine in
      xenograft tissues. CONCLUSIONS: Our experimental data suggest that continued
      moderate smoking and NRT may negatively impact therapeutic outcomes of
      gemcitabine on pancreatic cancer and that clinical studies in cancer patients are
      now warranted.

PMID- 23146956
TI  - Phase I pharmacokinetic and pharmacodynamic study of lapatinib in combination
      with sorafenib in patients with advanced refractory solid tumors.
AB  - BACKGROUND: The epidermal growth factor receptor (EGFR) and ERBB2 (HER2) pathways
      and vascular endothelial growth factor (VEGF)-dependent angiogenesis have a
      pivotal role in cancer pathogenesis and progression. Robust experimental evidence
      has shown that these pathways are functionally linked and implicated in acquired
      resistance to targeted therapies making them attractive candidates for joined
      targeting. We undertook this phase I trial to assess the safety, the recommended
      dose for phase II trials (RPTD), pharmacokinetics (PK), pharmacodynamics (PD),
      and the preliminary antitumour activity of the combination of lapatinib and
      sorafenib in patients with advanced refractory solid tumours. METHODS: Four
      cohorts of at least three patients each received lapatinib once daily and
      sorafenib twice daily together on a continuous schedule. Doses of lapatinib and
      sorafenib were escalated based on dose-limiting toxicities (DLTs) in the first
      treatment cycle following a traditional 3+3 design until the RPTD was reached.
      Additional patients were treated at the RPTD to characterise PK profiles of this
      combination and to investigate the potential interaction between lapatinib and
      sorafenib. Serum samples were collected at baseline and then prospectively every
      two cycles to assess changes in PD parameters. This trial is registered with
      ClinicalTrials.gov, number NCT00984425. FINDINGS: Thirty patients with advanced
      refractory solid tumours were enroled. DLTs were grade three fatigue and grade 3
      atypical skin rash observed at dose levels 3 and 4, respectively. The higher dose
      level explored (lapatinib 1250mg/day and sorafenib 400mg twice daily) represented
      the RPTD of the combination. The most common drug-related adverse events were
      fatigue (68%), hypocalcemia (61%), diarrhoea (57%), lymphopaenia (54%), anorexia
      (50%), rash (50%), and hypophosphatemia (46%). PK analysis revealed no
      significant effect of sorafenib on the PK profile of lapatinib. Of the 27
      assessable patients for clinical activity, one achieved a confirmed complete
      response, four (15%) had a partial response, and 12 (44%) achieved disease
      stabilisation. The disease control rate overall was 63%. INTERPRETATION:
      Combination treatment with lapatinib and sorafenib was feasible with promising
      clinical activity and without significant PK interactions. Long term tolerability
      seems to be challenging.

PMID- 23146957
TI  - X chromosome inactivation pattern in BRCA gene mutation carriers.
AB  - An association of preferential X chromosome inactivation (XCI) with BRCA gene
      status and breast/ovarian cancer risk has been reported. We evaluated XCI in a
      large group of BRCA mutation carriers compared to non-carriers and investigated
      associations between preferential XCI (?90:10) and age, mutated gene, cancer
      development and chemotherapy. XCI was analysed by human androgen receptor
      (HUMARA) assay and pyrosequencing in 437 BRCA1 or BRCA2 mutation carriers and 445
      age-matched controls. The distribution of XCI patterns in the two groups was
      compared by logistic regression analysis. The association between preferential
      XCI and selected variables was investigated in both univariate and multivariate
      fashion. In univariate analyses preferential XCI was not significantly associated
      with the probability of being a BRCA mutation carrier, nor with cancer status,
      whereas chemotherapeutic regime and age both showed a significant association. In
      multivariate analysis only age maintained significance (odds ratio, 1.056; 95%
      confidence interval, 1.016-1.096). Our findings do not support the usefulness of
      XCI analysis for the identification of BRCA mutation carriers and cancer risk
      assessment. The increasing preferential XCI frequency with ageing and the
      association with chemotherapy justify extending the investigation to other
      categories of female cancer patients to identify possible X-linked loci
      implicated in cell survival.

PMID- 23146958
TI  - Incidence of venous thromboembolism in patients with cancer - a cohort study
      using linked United Kingdom databases.
AB  - BACKGROUND: Accurate population-based data are needed on the incidence of venous
      thromboembolism (VTE) in patients with different cancers in order to inform
      guidelines on which hospitalised and ambulatory cancer patients should receive
      VTE prophylaxis. METHODS: We conducted a cohort study using data from the
      Clinical Practice Research Datalink, linked to Hospital Episode Statistics,
      Cancer Registry data and Office for National Statistics cause of death data. We
      determined the incidence rates (cases per 1000 person-years) of VTE separately
      for 24 cancer sites. To determine relative risk, incidence rates were compared to
      frequency-matched controls (by age) with no record of cancer. FINDINGS: We
      identified 83,203 cancer patients and 577,207 controls. New cases of VTE were
      diagnosed in 3352 cancer patients, and 6353 controls. The absolute rate of VTE in
      all cancers was 13.9 per 1000 person-years (95% confidence interval [CI] 13.4
      14.4), corresponding to an age, sex and calendar year adjusted hazard-ratio of
      4.7 (CI 4.5-4.9) between cancer patients and the general population. Rates varied
      greatly by cancer site (range; 98 (CI 80-119) in pancreatic cancer to 3.1 (CI 1.5
      6.5) in thyroid cancer), age (range; 16.9 for patients over 80 years to 4.9 for
      those under 30 years) and time from diagnosis (range; 75 in the first three
      months to 8.4, >1 year after diagnosis). INTERPRETATION: VTE is strongly linked
      to cancer, but the annual rate varies greatly by cancer site, proximity to
      diagnosis and age. Prophylaxis guidelines should take account of cancer site and
      such intervention should also be targeted towards the three months following
      diagnosis.

PMID- 23146959
TI  - Clinical significance of intratumoral HER2 heterogeneity in gastric cancer.
AB  - AIM: To evaluate the clinical significance of intratumoral HER2 heterogeneity in
      gastric cancer (GC). METHODS: A total of 322 GC tissues were evaluated by HER2
      immunohistochemistry (IHC), of which 73 with IHC 2+ or 3+ were subjected to
      fluorescence in situ hybridisation (FISH). Also, 3-5 distinct spots in each case
      showing different HER2 staining intensities were evaluated individually by
      comparing IHC staining intensity with gene copy number (GCN). Minimum, average
      and maximum FISH scores were generated for each case. RESULTS: Intratumoral
      heterogeneity of HER2 overexpression and gene amplification were 54 and 30 of 73
      cases with IHC 2+ or 3+, respectively. These cases were characterised by diffuse
      or mixed Lauren type, HER2 IHC 2+, and low-level amplification. Kaplan-Meier
      survival analysis revealed that the heterogeneous overexpression was
      significantly associated with longer disease-free survival times than the
      homogeneous, and the high average GCN was most associated with poor outcome.
      Also, there was a strong correlation between the IHC and FISH results for each
      spot. Quantitative polymerase chain reaction (PCR) analysis of the cancer tissues
      and the cell-free plasma showed that HER2 gene copy by quantitative PCR on tissue
      correlated well with those by FISH, but plasma HER2 level was not. CONCLUSIONS:
      Considering the high incidence of intratumoral HER2 heterogeneity in GC, accurate
      HER2 assessment would require larger tissues and more detailed guidelines. The
      guidelines should include the recommendation that FISH-scoring areas be selected
      with reference to a corresponding IHC slide. Also, the definition of HER2
      positive tumours should be reassessed considering the intratumoral heterogeneity.

PMID- 23146960
TI  - Do perinatal and early life exposures influence the risk of malignant melanoma? A
      Northern Ireland birth cohort analysis.
AB  - AIM: Intrauterine, early life and maternal exposures may have important
      consequences for cancer development in later life. The aim of this study was to
      examine perinatal and birth characteristics with respect to Cutaneous malignant
      melanoma (CMM) risk. METHODS: The Northern Ireland Child Health System database
      was used to examine gestational age adjusted birth weight, infant feeding
      practices, parental age and socioeconomic factors at birth in relation to CMM
      risk amongst 447,663 infants delivered between January 1971 and December 1986.
      Follow-up of histologically verified CMM cases was undertaken from the beginning
      of 1993 to 31st December 2007. Multivariable adjusted unconditional logistic
      regression was used to calculate odds ratios (OR) and 95% confidence intervals
      (CI) of CMM risk. RESULTS: A total of 276 CMM cases and 440,336 controls
      contributed to the final analysis. In reference to normal (gestational age
      adjusted) weight babies, those heaviest at birth were twice as likely to develop
      CMM OR 2.4 (95% CI 1.1-5.1). Inverse associations with CMM risk were observed
      with younger (<25 years) parental age at birth and both a higher birth order and
      greater household density OR 0.61 (95% CI 0.37-0.99) and OR 0.56 (95% CI 0.30
      1.0) respectively. CONCLUSION: This large study of early onset melanoma supports
      a positive association with higher birth weight (imperatively gestational age
      adjusted) and CMM risk which may be related to factors which drive intrauterine
      foetal growth. Strong inverse associations observed with higher birth order and
      household density suggest that early-life immune modulation may confer
      protection; findings which warrant further investigation in prospective analyses.

PMID- 23146962
TI  - A beautiful stroke? A side note on the 75th anniversary of the spectacular death
      of the French organist and composer Louis Vierne (1870-1937).
AB  - The great French organist and composer Louis Vierne (1870-1937) died while
      performing an organ recital at Notre Dame cathedral in Paris - right in front of
      the console. This historical article provides insights into the biography of a
      highly talented musician who was challenged by disability and diseases throughout
      his career. A special focus is placed on the circumstances of Vierne's remarkable
      death. Until now, both a primary cerebrovascular event and a 'heart attack' are
      discussed in reference books and encyclopedias as the immanent causes of death.
      From the perspective of a stroke neurologist, a reappraisal of Vierne's medical
      history and the events that happened during his last concert is presented.

PMID- 23146961
TI  - Relapses in hepatoblastoma patients: clinical characteristics and outcome-
      experience of the International Childhood Liver Tumour Strategy Group (SIOPEL).
AB  - PURPOSE: To analyse the clinical characteristics and outcome of hepatoblastoma
      (HB) patients who relapsed after enrolment on SIOPEL studies 1-3. PATIENTS AND
      METHODS: Analysis of clinical data of all 59 patients (pts) registered in SIOPEL
      1-3 studies, who relapsed after achieving complete remission (CR). RESULTS: The
      median time from the initial diagnosis to relapse was 12 months (4-115 m). The
      site of relapse was lung N=27, liver N=21, both liver and lung N=5 and other N=5
      (missing data-MD: 1 patient). All but 9 pts had an alpha-fetoprotein level >10
      ng/mL at the time of relapse. Treatment of the relapse included chemotherapy and
      surgery N=25, chemotherapy alone N=21, surgery alone N=7 and only palliative
      treatment N=5 (MD: 1 pt). Overall, 31 pts (52%) achieved a second CR. With a
      median follow-up of 83 months, 23 pts are alive, (18 in 2nd CR, 5 after a second
      relapse) and 36 pts have died (35 from disease and 1 from complications). Three
      year event-free survival and overall survival are 34% and 43% respectively (95%
      confidence interval [CI] 0.28-0.69). The main factors associated with a good
      outcome were PRETEXT group I-III at diagnosis, a high AFP level at relapse and
      relapse treatment including both chemotherapy and surgery. CONCLUSION: Relapses
      in HB are rare events occurring in less than 12% of pts after CR. Combined
      treatment with chemotherapy and surgical removal of the tumour is essential for
      long-term survival.

PMID- 23146963
TI  - Correspondence between stimulus encoding- and maintenance-related neural
      processes underlies successful working memory.
AB  - The ability to actively maintain information in working memory (WM) is vital for
      goal-directed behavior, but the mechanisms underlying this process remain
      elusive. We hypothesized that successful WM relies upon a correspondence between
      the neural processes associated with stimulus encoding and the neural processes
      associated with maintenance. Using functional magnetic resonance imaging, we
      identified regional activity and inter-regional connectivity during stimulus
      encoding and the maintenance of those stimuli when they were no longer present.
      We compared correspondence in these neural processes across encoding and
      maintenance epochs with WM performance. Critically, greater correspondence
      between encoding and maintenance in 1) regional activity in the lateral
      prefrontal cortex (PFC) and 2) connectivity between lateral PFC and extrastriate
      cortex was associated with increased performance. These findings suggest that the
      conservation of neural processes across encoding and maintenance supports the
      integrity of representations in WM. 

PMID- 23146964
TI  - Tracking whole-brain connectivity dynamics in the resting state.
AB  - Spontaneous fluctuations are a hallmark of recordings of neural signals, emergent
      over time scales spanning milliseconds and tens of minutes. However,
      investigations of intrinsic brain organization based on resting-state functional
      magnetic resonance imaging have largely not taken into account the presence and
      potential of temporal variability, as most current approaches to examine
      functional connectivity (FC) implicitly assume that relationships are constant
      throughout the length of the recording. In this work, we describe an approach to
      assess whole-brain FC dynamics based on spatial independent component analysis,
      sliding time window correlation, and k-means clustering of windowed correlation
      matrices. The method is applied to resting-state data from a large sample (n =
      405) of young adults. Our analysis of FC variability highlights particularly
      flexible connections between regions in lateral parietal and cingulate cortex,
      and argues against a labeling scheme where such regions are treated as separate
      and antagonistic entities. Additionally, clustering analysis reveals
      unanticipated FC states that in part diverge strongly from stationary
      connectivity patterns and challenge current descriptions of interactions between
      large-scale networks. Temporal trends in the occurrence of different FC states
      motivate theories regarding their functional roles and relationships with
      vigilance/arousal. Overall, we suggest that the study of time-varying aspects of
      FC can unveil flexibility in the functional coordination between different neural
      systems, and that the exploitation of these dynamics in further investigations
      may improve our understanding of behavioral shifts and adaptive processes. 

PMID- 23146967
TI  - Connectivity-based parcellation of the human posteromedial cortex.
AB  - Regional structural and functional variations in the posteromedial cortex (PMC)
      have been found in both animals and humans, strongly suggesting the presence of
      subdivisions. However, there is no consensus on how to subdivide the human PMC.
      Here, we investigated the anatomical parcellation scheme and the connectivity
      pattern of each subdivision of the human PMC using diffusion tensor imaging data
      from 2 independent groups of volunteers. The parcellation analyses of the 2
      datasets consistently demonstrated that the human PMC can be parcellated into 5
      subregions. The dorsal portion of the PMC was subdivided into anterior, central,
      and posterior subregions, which participate in sensorimotor, associative, and
      visual functions. The ventral PMC contained a transitional region in the dorsal
      portion and a ventral subregion that is the core of the default mode network. The
      parcellation results for the human PMC and its anatomical connectivity patterns
      were further supported by evidence from the macaque PMC. Furthermore, functional
      connectivity analysis revealed that each subregion exhibited a specific pattern
      similar to that of its anatomical connectivity. The proposed parcellation scheme
      may facilitate the study of the human PMC at a subtler level and improve our
      understanding of its functions. 

PMID- 23146965
TI  - The negative association of childhood obesity to cognitive control of action
      monitoring.
AB  - The global epidemic of childhood obesity has become a major public health
      concern. Yet, evidence regarding the association between childhood obesity and
      cognitive health has remained scarce. This study examined the relationship
      between obesity and cognitive control using neuroelectric and behavioral measures
      of action monitoring in preadolescent children. Healthy weight and obese children
      performed compatible and incompatible stimulus-response conditions of a modified
      flanker task, while task performance and the error-related negativity (ERN) were
      assessed. Analyses revealed that obese children exhibited a longer reaction time
      (RT) relative to healthy weight children for the incompatible condition, whereas
      no such difference was observed for the compatible condition. Further, obese
      children had smaller ERN amplitude relative to healthy weight children with lower
      post-error response accuracy. In addition, healthy weight children maintained
      post-error response accuracy between the compatible and incompatible conditions
      with decreased ERN amplitude in the incompatible condition, whereas obese
      children exhibited lower post-error response accuracy for the incompatible
      relative to the compatible condition with no change in ERN amplitude between the
      compatibility conditions. These results suggest that childhood obesity is
      associated with a decreased ability to modulate the cognitive control network,
      involving the prefrontal cortex and anterior cingulate cortex, which supports
      action monitoring. 

PMID- 23146966
TI  - Fear-specific amygdala function in children and adolescents on the fragile x
      spectrum: a dosage response of the FMR1 gene.
AB  - Mutations of the fragile X mental retardation 1 (FMR1) gene are the genetic cause
      of fragile X syndrome (FXS). The presence of significant socioemotional problems
      has been well documented in FXS although the brain basis of those deficits
      remains unspecified. Here, we investigated amygdala dysfunction and its relation
      to socioemotional deficits and FMR1 gene expression in children and adolescents
      on the FX spectrum (i.e., individuals whose trinucleotide CGG repeat expansion
      from 55 to over 200 places them somewhere within the fragile X diagnostic range
      from premutation to full mutation). Participants performed an fMRI task in which
      they viewed fearful, happy, and scrambled faces. Neuroimaging results
      demonstrated that FX participants revealed significantly attenuated amygdala
      activation in Fearful > Scrambled and Fearful > Happy contrasts compared with
      their neurotypical counterparts, while showing no differences in amygdala volume.
      Furthermore, we found significant relationships between FMR1 gene expression,
      anxiety/social dysfunction scores, and reduced amygdala activation in the FX
      group. In conclusion, we report novel evidence regarding a dosage response of the
      FMR1 gene on fear-specific functions of the amygdala, which is associated with
      socioemotional deficits in FXS. 

PMID- 23146969
TI  - Emergence of complex computational structures from chaotic neural networks
      through reward-modulated Hebbian learning.
AB  - This paper addresses the question how generic microcircuits of neurons in
      different parts of the cortex can attain and maintain different computational
      specializations. We show that if stochastic variations in the dynamics of local
      microcircuits are correlated with signals related to functional improvements of
      the brain (e.g. in the control of behavior), the computational operation of these
      microcircuits can become optimized for specific tasks such as the generation of
      specific periodic signals and task-dependent routing of information. Furthermore,
      we show that working memory can autonomously emerge through reward-modulated
      Hebbian learning, if needed for specific tasks. Altogether, our results suggest
      that reward-modulated synaptic plasticity can not only optimize the network
      parameters for specific computational tasks, but also initiate a functional
      rewiring that re-programs microcircuits, thereby generating diverse computational
      functions in different generic cortical microcircuits. On a more general level,
      this work provides a new perspective for a standard model for computations in
      generic cortical microcircuits (liquid computing model). It shows that the
      arguably most problematic assumption of this model, the postulate of a teacher
      that trains neural readouts through supervised learning, can be eliminated. We
      show that generic networks of neurons can learn numerous biologically relevant
      computations through trial and error. 

PMID- 23146970
TI  - Healthcare utilization and costs associated with skeletal-related events in
      prostate cancer patients with bone metastases.
AB  - BACKGROUND: Patients with bone metastases secondary to prostate cancer are
      predisposed to skeletal-related events (SREs), including spinal cord compression,
      pathological fracture, surgery to bone and radiotherapy to bone. The objective of
      this study was to document current patterns of healthcare utilization and costs
      of SREs in patients with prostate cancer and bone metastases. METHODS: This was a
      retrospective, observational study using the Thomson MedStat MarketScan
      Commercial Claims and Encounters database from September 2002 to June 2011. Study
      subjects included all persons with claims for prostate cancer and for bone
      metastases, and one or more claims for an SRE. Unique SRE episodes were
      identified based on a gap of at least 90 days without an SRE claim, and
      classified by treatment setting (inpatient or outpatient) and SRE type (spinal
      cord compression, pathological fracture, surgery to bone or radiotherapy).
      RESULTS: Of 3919 patients with prostate cancer and bone metastases, 2090 (53%)
      had one or more SRE episodes. Among 1237 patients who met all other criteria,
      there were 1623 SRE episodes over a mean (s.d.) follow-up of 16.1 (12.9) months.
      The percent of episodes that required inpatient treatment ranged from 14%
      (radiotherapy) to 82% (surgery to bone). On average, inpatient episodes with
      surgery to bone (n = 36 episodes) were most costly (mean (s.e.) $88,838
      ($11,830)/episode), whereas outpatient episodes with surgery to bone (n = 8
      episodes) were least costly (mean (s.e.) $4749 ($1690)/episode). Of the total SRE
      costs (mean (s.e.) $20,984 ($951)/episode), 41% were attributable to outpatient
      radiotherapy (n = 1169 episodes), 23% to inpatient radiotherapy (n = 184
      episodes), and 19% to inpatient treatment of pathological fractures (n = 101
      episodes). CONCLUSIONS: In patients with prostate cancer and bone metastases,
      SREs are associated with high costs and hospitalizations.

PMID- 23146968
TI  - Injury to the premature cerebellum: outcome is related to remote cortical
      development.
AB  - Cerebellar injury is an important complication of preterm birth with far-reaching
      neuropsychiatric sequelae. We have previously shown a significant association
      between isolated injury to the premature cerebellum and subsequent impairment of
      regional volumetric growth in the contralateral cerebrum. In the current study,
      we examine the relationship between these remote regional impairments of cerebral
      volumetric growth and domain-specific functional deficits in these children. In
      40 ex-preterm infants with isolated cerebellar injury, we performed
      neurodevelopmental evaluations and quantitative magnetic resonance imaging (MRI)
      studies at a mean age of 34 months. We measured cortical gray matter volumes in 8
      parcellated regions of each cerebral hemisphere, as well as right and left
      cerebellar volumes. We show highly significant associations between early signs
      of autism and dorsolateral prefrontal cortex volume (P < 0.001); gross motor
      scores and sensorimotor cortical volumes (P < 0.001); and cognitive and
      expressive language scores and premotor and mid-temporal cortical volumes (P <
      0.001). By multivariate analyses, each unit increase in the corresponding
      regional cerebral volume was associated with lower odds of abnormal outcome
      score, adjusted for age at MRI and contralateral cerebellar volume. This is the
      first report linking secondary impairment of remote cerebral cortical growth and
      functional disabilities in survivors of prematurity-related cerebellar brain
      injury. 

PMID- 23146972
TI  - Second to fourth digit ratio and prostate cancer severity.
AB  - BACKGROUND: The ratio of the second to the fourth digit (2D:4D ratio) is a
      sexually dimorphic trait established in utero that differs between ethnic groups.
      It is associated with prenatal androgen exposure, and studies have evaluated the
      ratio as a marker for certain traits and disease states known to be associated
      with higher levels of in utero androgens, such as prostate cancer. There are
      currently no screening tools that stratify men with prostate cancer according to
      the severity of their disease. This study aims to investigate the 2D:4D ratio as
      a potential marker for prostate cancer severity. Our hypothesis was that lower
      digit ratios, representing higher in utero androgen exposure, would be associated
      with more severe disease. METHODS: Measurements were taken of the second and
      fourth digits of the right hand of male patients diagnosed with prostate cancer.
      Gleason score, presence of metastasis, family history, age at diagnosis and race
      were recorded. The distribution of demographic and other patient characteristics
      were compared with digit ratios to determine relationships. RESULTS: African
      American men with prostate cancer are 3.70 times more likely to have a low 2D:4D
      digit ratio than Caucasian men with prostate cancer (95% confidence interval:
      1.98, 6.92; P < 0.0001). There were no statistically significant differences in
      the presence of metastasis, Gleason score, family history or age at diagnosis by
      digit ratio. CONCLUSION: 2D:4D ratio shows strong differences between African
      Americans and Caucasians; however, it does not correlate with disease severity in
      men already diagnosed with prostate cancer. Although this is a small population
      sample with possible confounding factors, it does not provide evidence to support
      the hypothesis that prenatal androgens affect prostate cancer grade or
      progression.

PMID- 23146971
TI  - Glutathione-S-transferase (GST) polymorphisms are associated with relapse after
      radical prostatectomy.
AB  - BACKGROUND: Organ confined prostate cancer (PCa) can be cured by radical
      retropubic prostatectomy (RRP); however, some tumors will still recur. Current
      tools fail to identify patients at risk of recurrence. Glutathione-S-transferases
      (GSTs) are involved in the metabolism of carcinogens, hormones and drugs. Thus,
      genetic polymorphisms that modify the GST activities may modify the risk of PCa
      recurrence. METHODS: We retrospectively recruited Argentine PCa patients treated
      with RRP to study the association between GST polymorphisms and PCa biochemical
      relapse after RRP. We genotyped germline DNA in 105 patients for: GSTP1 c.313A>G
      (p.105 Ile>Val, rs1695) by PCR-RFLP; and GSTT1 null and GSTM1 null polymorphisms
      by multiplex PCR. Kaplan-Meier curves and Cox proportional hazard models were
      used to evaluate these associations. RESULTS: Patients with GSTP1 c.313GG
      genotype showed shorter biochemical relapse-free survival (BRFS) (P = 0.003) and
      higher risk for recurrence in unadjusted (Hazard ratio (HR) = 3.16, 95%
      confidence interval (95% CI) = 1.41-7.06, P = 0.005) and multivariate models (HR
      = 3.01, 95% CI = 1.13-8.02, P = 0.028). We did not find significant associations
      for GSTT1 and GSTM1 genotypes. In addition, we found shorter BRFS (P = 0.010) and
      increased risk for recurrence for patients having two or more risk alleles when
      we combined the genotypes of the three GSTs in multivariate models (HR = 3.06,
      95% CI = 1.20-7.80, P = 0.019). CONCLUSIONS: Our results give support to the
      implementation of GSTs genotyping for personalized therapies as a novel
      alternative for PCa management for patients who undergo RRP. To the best of our
      knowledge, this is the first study that examined GST polymorphisms in PCa
      progression in Argentine men. Replication of our findings in larger cohort is
      warranted.

PMID- 23146973
TI  - Serum pentraxin-3 levels are associated with the severity of metabolic syndrome.
AB  - OBJECTIVES: The aim of the present study was to assess the association between
      the level of pentraxin-3 (PTX-3) and the severity of metabolic syndrome (MS).
      SUBJECTS AND METHOD: One hundred and two patients with MS and 101 consecutive age
      and sex-matched control subjects were included in the study. The MS patients
      were classified into three groups based on the number of MS criteria, i.e. group
      1: patients with 3 MS criteria, group 2: patients with 4 MS criteria, and group
      3: patients with 5 MS criteria. Serum PTX-3 and high-sensitivity C-reactive
      protein (hs-CRP) levels were measured. RESULTS: Group 1 had higher PTX-3 levels
      compared to the control group (0.58 +/- 0.11 ng/ml vs. 0.36 +/- 0.15 ng/ml, p <
      0.001). PTX-3 levels were higher in group 3 than in both group 1 (0.90 +/- 0.06
      ng/ml vs. 0.58 +/- 0.11 ng/ml, p < 0.001) and group 2 (0.90 +/- 0.06 ng/ml vs.
      0.63 +/- 0.12 ng/ml, p < 0.001). Group 3, however, had higher hs-CRP levels than
      both group 1 (1.89 +/- 0.45 mg/dl vs. 1.40 +/- 0.44 mg/dl, p = 0.007) and group 2
      (1.89 +/- 0.45 mg/dl vs. 1.47 +/- 0.58 mg/dl, p = 0.01). The control group had
      lower hs-CRP levels than group 1 (0.81 +/- 0.47 mg/dl vs. 1.40 +/- 0.44 mg/dl, p
      < 0.001) and group 2 (0.81 +/- 0.47 mg/dl vs. 1.47 +/- 0.58 mg/dl, p < 0.001).
      Serum PTX-3 levels correlated with serum hs-CRP levels (r = 0.49, p < 0.001).
      CONCLUSIONS: PTX-3, a novel inflammatory marker, was found to be associated with
      the severity of MS.

PMID- 23146974
TI  - Shall we stop or continue angiotensin-converting enzyme inhibitors and
      angiotensin receptor blockers prior to using contrast agents?

PMID- 23146975
TI  - Assessment of peripheral vascular disease in patients with chronic kidney
      disease.

PMID- 23146976
TI  - Depression among dialysis patients: barriers to good care.

PMID- 23146977
TI  - Botanical medicines used for kidney disease in the United States.
AB  - Herbal medicines are being used with greater frequency by practitioners of
      natural medicine in the United States. Many categories of herbs are used,
      primarily angiotensin antagonists, nonspecific nephroprotective, and
      immunomodulating/adaptogenic herbs. The most common herbs in each category are
      discussed both from a historical and scientific perspective. For the first time,
      a case series of the use of the proposed herbal angiotensin antagonist herb
      indigenous to the United States, Lespedeza capitata, is reported based on the
      author's clinical practice.

PMID- 23146978
TI  - A novel target for diuretic therapy.
AB  - The reabsorption of salt in the distal nephron is predominantly mediated via the
      thiazide-sensitive sodium chroride cotransporter, NCC (SLC12A3), and the chloride
      bicarbonate exchanger pendrin (SLC26A4, PDS), with pendrin working in tandem with
      the epithelial sodium channel and NCC working by itself. Single deletion of NCC
      or pendrin in genetically engineered mouse models does not cause salt wasting or
      excessive diuresis under basal conditions. Both pendrin knockout and NCC knockout
      mice, however, show signs of volume depletion or develop hypotension during salt
      restriction. These findings have led investigators to conclude that pendrin and
      NCC are predominantly active during salt depletion and their contribution to salt
      reabsorption at baseline conditions is small. We hypothesized that pendrin may
      compensate for loss of NCC under basal conditions, thereby masking the role that
      each transporter plays in salt reabsorption. To test this hypothesis, double
      knockout of pendrin and sodium chloride cotransporter was generated by crossing
      animals with single deletion for NCC and pendrin. The double-knockout mice show
      significant salt and fluid wasting, along with severe volume depletion, metabolic
      alkalosis and prerenal failure under baseline conditions. Volume depletion,
      metabolic alkalosis and prerenal failure were significantly corrected with salt
      repletion. We conclude that pendrin plays an essential role in the distal tubule
      salt reabsorption in the setting of sodium-chloride cotransporter inactivation.
      We propose that pendrin could be a novel target for a new diuretic that in
      conjunction with thiazide can be an effective regimen for patients with fluid
      overload.

PMID- 23146979
TI  - Histopathologic and clinical findings of congenital nephrotic syndrome in Iranian
      children: a study of two centers.
AB  - INTRODUCTION: Congenital nephrotic syndrome (CNS), an uncommon form of kidney
      disease, presents during the first year of life and is a diagnostic and
      therapeutic challenge for the pediatricians as well as pediatric nephrologists.
      Our study is the first study of Iranian children with CNS in two pediatric
      nephrology centers in Tehran, Iran. MATERIALS AND METHODS: We reviewed medical
      charts of 30 infants diagnosed with CNS from 1990 to 2005. RESULTS: There were 15
      boys and 15 girls with CNS (mean age, 1.7 months). The presentation of the
      disease was nephrotic syndrome in 96.6% of the patients. Eighty percent of the
      patients presented within 3 months of life and 16 in the neonatal period. The
      Finnish type of CNS was seen in 43.3% and diffuse mesangial sclerosis in 50%.
      Preterm labor and low birth weight was seen in 20%. A family history of nephrotic
      syndrome in infancy was noted for 8 children (26.7%). Numerous complications of
      nephrotic syndrome occurred in 73.3%. Seventy percent of the patients had 27
      episodes of infections. Sepsis was seen in 43.3% of the children, of which 61.5%
      were caused by gram-negative bacteria and 38.6% were caused by Staphylococcus
      aureus. Thrombotic complications and hypertension developed in 6.6% and 23.3% of
      the patients, respectively. The mortality rate of patients was 86.6%.
      CONCLUSIONS: Diffuse mesangial sclerosis is an important cause of CNS. The
      outcome of our patients was poor and most of our patients died before reaching
      the age of 5 years old.

PMID- 23146981
TI  - Clinicopathologic correlations in Henoch-Schonlein nephritis.
AB  - INTRODUCTION: Renal involvement is the major cause of mortality and morbidity in
      children with Henoch-Schonlein purpura. The purpose of this study was to
      determine the predictive factors of Henoch-Schonlein nephritis (HSN) and
      correlations between clinical and pathologic findings. MATERIALS AND METHODS:
      Demographic characteristics and clinical manifestations of 105 children with
      Henoch-Schonlein purpura were retrospectively evaluated. Kidney biopsy with
      pathologic scoring was performed in 17 patients. RESULTS: Sixty-one boys and 44
      girls were included in this study. The mean age at presentation was 73.0 +/- 33.4
      months (range, 12 to 156 months). Thirty-nine percent of patients had renal
      involvement. Their mean age at presentation of HSN was 87.4 +/- 30.9 months,
      which was significantly higher than the age of those without nephritis. Age at
      presentation was the only predictor of renal involvement. Hematuria and
      proteinuria were the most common laboratory findings of HSN, followed by
      nephrotic syndrome and acute nephritis. The most common histologic findings were
      grades 3 (especially 3B) and 2 of the International Study of Kidney Disease in
      Children classification, respectively. Higher pathologic grades were more
      frequent in patients with nephrotic syndrome and acute nephritis. Similarly,
      there was a positive relationship between the severity of proteinuria and both
      pathologic grading and scoring, especially crescent formation, endocapillary
      proliferation, and tubular atrophy. CONCLUSIONS: There was a significant
      correlation between the severity of renal involvement and pathologic grading and
      scoring in HSN. The severity of proteinuria was a significant determinant of
      renal pathologic findings.

PMID- 23146980
TI  - Effect of renin-angiotensin-aldosterone system blockade therapy on incidence of
      contrast-induced nephropathy in patients with chronic kidney disease.
AB  - INTRODUCTION: The incidence of contrast-induced nephropathy (CIN) ranges between
      10% and 50% among high-risk patients. Whether medications that affect rennin
      angiotensin-aldosterone system (RAAS) have any impact on the development of CIN
      remains uncertain. MATERIALS AND METHODS: We performed a retrospective study of
      patients with CKD stages 3 and 4 who were either on or off RAAS blockade therapy
      at the time of coronary angiography. Development of CIN was defined by a 25%
      increase of serum creatinine from baseline or an increase in serum creatinine by
      0.5 mg/dL from baseline. Serum creatinine values were recorded before contrast
      exposure and for 5 days after coronary angiography. RESULTS: A total of 178
      patients with CKD who had coronary angiography during the study period were
      included, of whom 62 (35%) were on ACE inhibitors, 12 (7%) were on ARBs, and 1
      (1%) was on combination of ACE inhibitors and ARBs. The estimated glomerular
      filtration rate was 44.0 +/- 11.5 mL/min. The odds ratio of acute kidney failure
      on day 5 was 0.73 (95% confidence interval, 0.31 to 1.69) for the ACE inhibitors
      and 0.46 (95% confidence interval, 0.06 to 3.70) for ARBs. Multivariable analysis
      revealed the findings to be independent of demographic variables, comorbidities,
      type of contrast medium, and the prophylactic strategies. CONCLUSIONS: Patients
      on RAAS blockade therapy before contrast exposure did not have an increased
      incidence of CIN. There was also no increased incidence of CIN with ACE
      inhibitors or ARBs in the subgroups at higher risk, such as those with diabetes
      mellitus.

PMID- 23146982
TI  - Prevalence of peripheral arterial disease in hemodialysis patients.
AB  - INTRODUCTION: The ankle-brachial index (ABI), measurement of carotid artery
      intima-media thickness (CIMT), and assessment of the thickness of
      interventricular septum (IVS), are noninvasive methods used to predict
      subclinical atherosclerosis in hemodialysis patients. This study aimed to
      determine the prevalence of peripheral arterial disease and to assess the
      correlations between ABI, CIMT, the thickness of IVS, and blood parameters in
      hemodialysis patients. MATERIALS AND METHODS: The ABI, CIMT, and the thickness of
      IVS were measured in 50 patients on hemodialysis. Data were collected regarding
      the levels of calcium, urine nitrogen, low-density lipoprotein cholesterol, high
      density lipoprotein cholesterol, triglyceride, cholesterol, creatinine, albumin
      in serum, as well as erythrocyte sedimentation rate. Results. Ten percent of the
      patients showed a reduced ABI (< 0.9). The mean values for ABI, CIMT, and IVS
      were 1.09 +/- 0.13, 0.68 +/- 0.11 mm, and 9.83 +/- 1.65 mm, respectively. The
      levels of calcium, cholesterol, low-density lipoprotein cholesterol, high-density
      lipoprotein cholesterol, and triglyceride in the serum of the patients with
      normal ABI were significantly higher than in patients with reduced ABI. There was
      a negative correlation between ABI and levels of serum LDLC (r = -0.29, P = .04)
      and triglyceride (r = -0.32, P = .02). Conclusions. The prevalence of peripheral
      arterial disease in the patients with CRF was 10% and it was correlated with
      several classical risk factors for atherosclerosis, including elevated LDL and
      cholesterol levels. CIMT and the thickness of IVS showed no apparent association
      with ABI.

PMID- 23146983
TI  - Citalopram versus psychological training for depression and anxiety symptoms in
      hemodialysis patients.
AB  - INTRODUCTION: This study was designed to compare an antidepressant medication,
      citalopram, with psychological training in hemodialysis patients with symptoms of
      anxiety and depression. MATERIALS AND METHODS: A total number of 44 hemodialysis
      patients scored 8 and more on the Hospital Anxiety and Depression Scale (HADS)
      were randomly allocated to two groups to receive citalopram, 20 mg/d, for 3
      months or to attend 6 sessions of 1-hour psychological training. A nephrologist
      and a senior psychiatry resident were responsible for training of the patients,
      which contained explaining the anatomy of the kidneys, causes of kidney failure,
      treatment modalities, the mechanism involved in hemodialysis, the required care
      in hemodialysis patients, stages of adaptive reaction in human, and techniques of
      problem solving, stress management, and muscle relaxation. Both groups completed
      the HADS once before and once after the treatment. The final results of the two
      groups were compared. RESULTS: Citalopram administration led to a significant
      decrease in the patients' depression score (P = .001), anxiety score (P = .048),
      and total HADS score (P = .002). Psychological training sessions also decreased
      significantly depression (P = .04), anxiety (P = .03), and total HADS scores (P =
      .045). There was no significant difference in the amount of decrease in the
      scores of depression (P = .65), anxiety (P = .19), and the total HADS (P = .66)
      between the two groups. CONCLUSIONS: Psychological training and citalopram have
      similar effects on improving the symptoms of anxiety and depression in
      hemodialysis patients.

PMID- 23146984
TI  - Long-term survival of patients with end-stage renal disease on maintenance
      hemodialysis: a multicenter study in Iran.
AB  - INTRODUCTION: Although maintenance dialysis in patients with end-stage renal
      disease prevents death from uremia, patient survival remains an important issue.
      This study is the first in Iran to evaluate long-term survival of patients with
      ESRD. MATERIALS AND METHODS: This retrospective study was conducted on 1861
      patients with ESRD referred to 12 hemodialysis centers in Khuzestan province,
      Iran. The period of study was 21 years, which was between 1989 to may 2010. The
      median follow-up duration was 46.0 months. Patients who died within 90 days of
      commencing dialysis were excluded. The patient's death as outcome measure was
      recorded and the survival was estimated by the Kaplan-Meier method. RESULTS: The
      mean age of 1861 patients at initiation of hemodialysis was 51.2 +/- 17.2 years,
      and 1120 were men (60.2%). Diabetes mellitus (32.9%) and hypertension (24.1%)
      were the most common known causes of ESRD in our patients. Regardless of the
      cause of ESRD, 1-, 5-, 10-, and 15-year survival of hemodialysis patients was
      83%, 25.2%, 3.8%, and 1.0% respectively. Survival of diabetic patients was
      significantly lower than nondiabetic patients (P <.001) and no one of diabetic
      patients survived up to 10 years. CONCLUSIONS: Based on our findings, the
      survival of ESRD patients undergoing hemodialysis in Iran is relatively poor,
      especially among diabetics. This can be explained by socioeconomic differences
      and the fact that dialysis patients who are otherwise healthy and are more likely
      to survival for a longer time have higher chances of receiving a kidney
      transplant in Iran.

PMID- 23146985
TI  - Impact of hemodialysis on visual parameters in patients with end-stage renal
      disease.
AB  - INTRODUCTION: Patients with end-stage renal disease who receive hemodialysis are
      prone to visual disturbances. The aim of this study was to evaluate the effects
      of metabolic changes on visual parameters during hemodialysis sessions. MATERIALS
      AND METHODS: Demographic information including history of underlying diseases,
      wearing eyeglasses, any ocular diseases or surgeries, and hemodialysis duration
      and frequency were recorded in 65 hemodialysis patients. The best corrected
      visual acuity (BCVA) in logarithm of the minimum angle of resolution and
      spherical equivalent (SE) per diopter were measured before and after
      hemodialysis. Other systemic and metabolic parameters including systolic blood
      pressure, body weight, KT/V, and blood levels of glucose, urea, and sodium were
      recorded. RESULTS: A total of 130 eyes of 38 men and 27 women with ages ranged
      from 24 to 90 years (mean, 60.3 +/- 16.7 years) were enrolled. The mean BCVA
      changed significantly after hemodialysis (0.29 +/- 0.48 increased to 0.31 +/-
      0.49; P < .001). The mean SE changes were significant as well (-0.33 +/- 0.31 D
      decreased to -0.40 +/- 0.12 D; P < .001). There was a weakly positive correlation
      between the BCVA and blood glucose changes (P = .05, r = 0.166). There were
      significant associations between diabetic retinopathy and wearing of eyeglasses
      with BCVA and SE (P < .001 for both). CONCLUSIONS: Hemodialysis could influence
      on visual parameters such as BCVA and refractive status by means of changes in
      blood glucose or possibly other systemic parameters.

PMID- 23146986
TI  - Segmental renal artery thrombosis secondary to methylene tetrahydrofolate
      reductase mutation: an unusual presentation.
AB  - Methylene tetrahydrofolate reductase (MTHFR) is an enzyme involved in the
      metabolism of homocysteine to methionine, and folic acid is an essential
      cofactor. Mutations in the MTHFR gene lead to hyperhomocysteinemia and vascular
      thrombosis. Heterozygous mutation involving a single nucleotide polymorphism in
      the MTHFR gene leading to vascular thrombosis is very rare. We present a case of
      segmental renal artery thrombosis secondary to this mutation and to the best of
      our knowledge, it is the first case to be reported. Though easily treatable, this
      is a condition which is seldom investigated in the workup of thrombotic
      disorders.

PMID- 23146987
TI  - Hemophagocytic [corrected] lymphohistiocytosis associated with nephrotic syndrome
      and multi-organ failure.
AB  - Hemophagocytic lymphohistiocytosis (HLH) is still an important elusive and
      misdiagnosed condition despite of improved knowledge. Nephrotic syndrome
      associated with HLH is not a common feature and has been rarely reported in
      hemophagocytic syndrome. We report a 27-year-old man with HLH who progressed to
      multi-organ failure as well as nephrotic-range proteinuria, generalized edema,
      and hypoalbuminemia.

PMID- 23146988
TI  - Re: Protective effect of heparin and aspirin against vascular thrombosis in
      pediatric kidney transplants.

PMID- 23146994
TI  - Characterizing infarction and selective neuronal loss following temporary focal
      cerebral ischemia in the rat: a multi-modality imaging study.
AB  - BACKGROUND AND PURPOSE: Current models dictate that, depending on occurrence of
      early reperfusion, the ischemic penumbra either undergoes or escapes infarction
      (i.e., "pan-necrosis"). However, tissue outcome following temporary middle
      cerebral artery occlusion (tMCAo) in rodents can also include selective neuronal
      loss (SNL), which even if subtle may impede functional recovery. In order to
      explore the pathophysiology of ischemic stroke, determine potential therapeutic
      targets and monitor effects of therapy, in vivo imaging surrogates of these
      varied histopathological outcomes applicable in the clinical setting would be
      useful. Although hyperintense signal on T(2)-weighted MRI in the chronic post
      stroke stage is considered a reliable surrogate of tissue infarction, SNL is not
      associated with T(2)W abnormal signal. In the clinical setting, the neuron
      specific PET ligand (11)C-flumazenil (FMZ) has been used to identify both pan
      necrosis and peri-infarct SNL, but this inference has not been histopathological
      confirmed so far. Here we investigated the late tissue sequelae of tMCAo in the
      rodent using in vivo T(2)W MRI and FMZ-PET against post mortem
      immunohistochemistry as gold standard. METHODS: Adult spontaneously hypertensive
      rats (SHRs) underwent 45 min distal-clip middle-cerebral artery occlusion and, 28
      days later, FMZ-PET and T(2)W-MRI, immediately followed by immunohistochemistry
      for neuronal loss (NeuN), activated microglia and astrocytosis. Based on standard
      histopathological definitions, ischemic lesions were classified into pan
      necrosis, partial infarction or SNL. NeuN changes and FMZ binding across the
      whole hemisphere were quantified in the same set of 44 regions-of-interest
      according to previously validated protocols; linear regressions between these two
      measures were carried out both within and across subjects. RESULTS: Both cortical
      pan-necrosis/partial infarction and SNL were present in all rats except one,
      where SNL was isolated and extensive. Infarction/partial infarction, but not SNL,
      was associated with T(2)W hyperintense signals and cortical atrophy. In contrast,
      FMZ binding was decreased in all types of lesions including SNL, in proportion
      with NeuN staining intensity both within (p<0.05 to <0.001) and across (p<0.001)
      subjects, including the subject that showed pure SNL (p=0.01). CONCLUSION: This
      novel study revealed three main facts: i) long-term histopathological cortical
      changes following 45 min tMCAo in SHRs included all three of SNL, partial
      infarction and frank infarction; ii) T2W MRI showed conspicuous high signal
      lesions for complete or partial infarction, but no changes for SNL; and iii) FMZ
      PET was sensitive to all three types of tMCAo-induced histopathological changes,
      including isolated SNL, suggesting it is a valid surrogate for the histological
      sequelae of focal cerebral ischemia. In addition, the finding of almost universal
      completed cortical infarction at 28 days differed from our previous findings at
      14-day survival using the same model and rat strain, where SNL was the almost
      exclusive outcome, possibly representing delayed infarct maturation. Prospective
      studies are needed to investigate this interesting possibility.

PMID- 23146995
TI  - Roles of glial cells in schizophrenia: possible targets for therapeutic
      approaches.
AB  - Glial cells consisting of oligodendrocytes, astrocytes, microglia, and NG2
      positive cells are major cell populations in the central nervous system, number
      wise. They function as effectors and modulators of neurodevelopment through a
      wide variety of neuron-glial cell interactions in brain development and
      functions. Glial cells can be affected by both genetic and environmental factors,
      leading to their dysfunctions in supporting neuronal development and functions.
      These in turn can affect neuronal cells, causing alterations at the circuitry
      level that manifest as behavioral characteristics associated with schizophrenia
      in late teens-early twenties. Glial cells are also involved in neuroinflammatory
      processes, which sometimes have deleterious effects on the normal brain
      development. If the glial involvement plays significant roles in schizophrenia,
      the processes involving glial cells can become possible therapeutic targets for
      schizophrenia. A number of known antipsychotics are shown to have beneficial
      effects on glial cells, but other drugs targeting glial cell functions may also
      have therapeutic effects on schizophrenia. The latter can be taken into
      consideration for future drug development for schizophrenia.

PMID- 23146993
TI  - Delayed hyperbaric oxygen therapy induces cell proliferation through
      stabilization of cAMP responsive element binding protein in the rat model of MCAo
      induced ischemic brain injury.
AB  - Treatments that could extend the therapeutic window of opportunity for stroke
      patients are urgently needed. Early administration of hyperbaric oxygen therapy
      (HBOT) has been proven neuroprotective in the middle cerebral artery occlusion
      (MCAo) in rodents. Our aim was to determine: 1) whether delayed HBOT after
      permanent MCAo (pMCAo) can still convey neuroprotection and restorative cell
      proliferation, and 2) whether these beneficial effects rely on HBO-induced
      activation of protein phosphatase-1gamma (PP1-gamma) leading to a decreased
      phosphorylation and ubiquitination of CREB and hence its stabilization. The
      experiments were performed in one hundred thirty-two male Sprague-Dawley rats
      with the body weight ranging from 240 to 270 g. Permanent MCAo was induced with
      the intraluminal filament occluding the right middle cerebral artery (MCA). In
      the first experiment, HBOT (2.5 ATA, 1h daily for 10 days) was started 48 h after
      pMCAo. Neurobehavioral deficits and infarct size as well as cyclic AMP response
      element-binding protein (CREB) expression and BrdU-DAB staining in the
      hippocampus and the peri-infarct region were evaluated on day 14 and day 28 post
      MCAo. In the second experiment, HBOT (2.5 ATA, 1h) was started 3h after pMCAo.
      The effects of CREB siRNA or PP1-gamma siRNA on HBO-induced infarct size
      alterations and target protein expression were studied. HBOT started with 48 h
      delay reduced infarct size, ameliorated neurobehavioral deficits and increased
      protein expression of CREB, resulting in increased cell proliferations in the
      hippocampus and peri-infarct region, on day 14 and day 28 post-MCAo. In the acute
      experiment pMCAo resulted in cerebral infarction and functional deterioration and
      reduced brain expression of PP1-gamma, which led to increased phosphorylation and
      ubiquitination of CREB 24h after MCAo. However HBOT administered 3h after
      ischemia reversed these molecular events and resulted in CREB stabilization,
      infarct size reduction and neurobehavioral improvement. Gene silencing with CREB
      siRNA or PP1-gamma siRNA reduced acute beneficial effects of HBO. In conclusion,
      delayed daily HBOT presented as potent neuroprotectant in pMCAo rats, increased
      CREB expression and signaling activity, and bolstered regenerative type cell
      proliferation in the injured brain. As shown in the acute experiment these
      effects of HBO were likely to be mediated by reducing ubiquitin-dependent CREB
      degradation owing to HBO-induced activation of PP1gamma.

PMID- 23146996
TI  - 2-Pyridylmethyl ether: a readily removable and efficient directing group for
      amino acid ligand accelerated ortho-C-H olefination of phenols.
AB  - 2-Pyridylmethyl ether-directed ortho-C-H olefination of phenols via a seven
      membered cyclopalladated intermediate has been disclosed to construct a variety
      of ortho-alkenyl phenols and ortho-alkyl phenols.

PMID- 23146997
TI  - Adaptive efficient compression of genomes.
AB  - : Modern high-throughput sequencing technologies are able to generate DNA
      sequences at an ever increasing rate. In parallel to the decreasing experimental
      time and cost necessary to produce DNA sequences, computational requirements for
      analysis and storage of the sequences are steeply increasing. Compression is a
      key technology to deal with this challenge. Recently, referential compression
      schemes, storing only the differences between a to-be-compressed input and a
      known reference sequence, gained a lot of interest in this field. However, memory
      requirements of the current algorithms are high and run times often are slow. In
      this paper, we propose an adaptive, parallel and highly efficient referential
      sequence compression method which allows fine-tuning of the trade-off between
      required memory and compression speed. When using 12 MB of memory, our method is
      for human genomes on-par with the best previous algorithms in terms of
      compression ratio (400:1) and compression speed. In contrast, it compresses a
      complete human genome in just 11 seconds when provided with 9 GB of main memory,
      which is almost three times faster than the best competitor while using less main
      memory.

PMID- 23146998
TI  - Copper-catalyzed synthesis of benzocarbazoles via alpha-C-arylation of ketones.
AB  - A simple and efficient copper-catalyzed method for the synthesis of 11H
      benzo[a]carbazoles has been developed. The protocol uses readily available
      substituted 2-(2-bromophenyl)-1H-indoles and ketones as starting materials and an
      inexpensive catalyst system. The corresponding 11H-benzo[a]carbazoles were
      obtained in moderate to excellent yields.

PMID- 23146999
TI  - Minimum effective volume of lidocaine for double-injection ultrasound-guided
      axillary block.
AB  - BACKGROUND: The aim of this study was to determine the minimum effective volume
      of lidocaine 1.5% with epinephrine 5 MUg/mL in 90% of patients (MEV90) for double
      injection ultrasound-guided axillary block (AXB). METHODS: All subjects received
      a double-injection ultrasound-guided AXB with lidocaine 1.5% and epinephrine 5
      MUg/mL. A 17-gauge, 8-cm Tuohy needle was initially advanced until its tip was
      positioned next to the musculocutaneous nerve. Volume assignment was carried out
      using a biased coin design up-and-down sequential method, where the volume of
      local anesthetic administered to each patient depended on the response of the
      previous one. In case of failure, the next subject received a higher volume
      (defined as the previous volume with an increment of 1.0 mL). If the previous
      patient had a successful block, the next subject was randomized to a lower volume
      (defined as the previous volume with a decrement of 1.0 mL), with a probability
      of b = 0.11, or the same volume, with a probability of 1 - b = 0.89. After
      injection of the musculocutaneous nerve, the needle was redirected toward the
      dorsal aspect of the axillary artery. For this second injection, volume
      assignment was carried out in a similar fashion; however, volume
      increments/decrements were 3.0 instead of 1.0 mL. Using a composite scale
      encompassing sensory and motor block, success was defined, at 30 minutes, as a
      composite score of 4 points (out of 4 points), and 10 points (out of 12 points)
      for the musculocutaneous and perivascular injection, respectively. Patients
      undergoing surgery of the forearm, wrist, or hand were prospectively enrolled
      until 45 successful musculocutaneous blocks or 45 successful perivascular
      injections were obtained. RESULTS: Fifty patients were included in the study.
      Using isotonic regression and bootstrap confidence interval (CI), the MEV90 was
      estimated to be 5.5 mL (95% CI, 3.0-6.7 mL) and 23.5 mL (95% CI, 23.1-23.9 mL)
      for the musculocutaneous and perivascular injection, respectively. CONCLUSIONS:
      For double-injection ultrasound-guided AXB, the MEV90 of lidocaine 1.5% with
      epinephrine 5 MUg/mL is 5.5 and 23.5 mL for the musculocutaneous nerve and
      perivascular injection, respectively. Further dose-finding studies are required
      for other concentrations of lidocaine, other local anesthetic agents, and other
      techniques for ultrasound-guided AXB.

PMID- 23147000
TI  - Design and optimization of the oriented groove on the hip implant surface to
      promote bone microstructure integrity.
AB  - We proposed a novel surface modification for an artificial hip joint stem from
      the viewpoint of maintenance and establishment of appropriate bone function and
      microstructure, represented by the preferred alignment of biological apatite
      (BAp) and collagen (Col). Oriented grooves were introduced into the proximal
      medial region of the femoral stem to control the principal stress applied to the
      bone inside the grooves, which is a dominant factor contributing to the promotion
      of Col/BAp alignment. The groove angle and the stem material were optimized based
      on the stress inside the grooves through a finite element analysis (FEA). Only
      the groove oriented proximally by 60 degrees  from the normal direction of the
      stem surface generated the healthy maximum principal stress distribution. The
      magnitude of the maximum principal stress inside the groove decreased with
      increasing the stem Young's modulus, while the direction of the stress did not
      largely changed. An in vivo implantation experiment showed that this groove was
      effective in inducing the new bone with preferential Col/BAp alignment along the
      groove depth direction which corresponded to the direction of maximum principal
      stress inside the groove. The anisotropic principal stress distribution and the
      oriented microstructure inside the groove are similar to those found in the
      femoral trabeculae; therefore, the creation of the oriented groove is a potent
      surface modification for optimizing implant design for a long-term fixation.

PMID- 23147001
TI  - Metal N-heterocyclic carbene complexes as potential antitumor metallodrugs.
AB  - The discovery of cisplatin's antitumor activity in 1969 prompted the search for
      novel metal-containing complexes as potential anticancer drugs. Among these novel
      complexes, metal N-heterocyclic carbene (NHC) complexes have recently gained
      considerable attention because they perfectly fit prerequisites for efficient
      drug design and fast optimization. Moreover, most of them have shown higher
      cytotoxicity than cisplatin. This review describes the advances that have been
      achieved in using transition metal (Ag, Au, Pt, Pd, Cu, Ni, and Ru) complexes
      containing NHC ligands as antitumor agents. Their modes of action at the cellular
      lever are further discussed. All these initial achievements clearly demonstrate
      the great potential of metal-NHC complexes as antitumor agents.

PMID- 23147002
TI  - Modern psychiatric treatment: a tribute to Thomas Detre, MD (1924-2011).

PMID- 23147003
TI  - Optogenetic and potassium channel gene therapy in a rodent model of focal
      neocortical epilepsy.
AB  - Neocortical epilepsy is frequently drug-resistant. Surgery to remove the
      epileptogenic zone is only feasible in a minority of cases, leaving many patients
      without an effective treatment. We report the potential efficacy of gene therapy
      in focal neocortical epilepsy using a rodent model in which epilepsy is induced
      by tetanus toxin injection in the motor cortex. By applying several complementary
      methods that use continuous wireless electroencephalographic monitoring to
      quantify epileptic activity, we observed increases in high frequency activity and
      in the occurrence of epileptiform events. Pyramidal neurons in the epileptic
      focus showed enhanced intrinsic excitability consistent with seizure generation.
      Optogenetic inhibition of a subset of principal neurons transduced with
      halorhodopsin targeted to the epileptic focus by lentiviral delivery was
      sufficient to attenuate electroencephalographic seizures. Local lentiviral
      overexpression of the potassium channel Kv1.1 reduced the intrinsic excitability
      of transduced pyramidal neurons. Coinjection of this Kv1.1 lentivirus with
      tetanus toxin fully prevented the occurrence of electroencephalographic seizures.
      Finally, administration of the Kv1.1 lentivirus to an established epileptic focus
      progressively suppressed epileptic activity over several weeks without detectable
      behavioral side effects. Thus, gene therapy in a rodent model can be used to
      suppress seizures acutely, prevent their occurrence after an epileptogenic
      stimulus, and successfully treat established focal epilepsy.

PMID- 23147004
TI  - Organization of the BcgI restriction-modification protein for the transfer of one
      methyl group to DNA.
AB  - The Type IIB restriction-modification protein BcgI contains A and B subunits in a
      2:1 ratio: A has the active sites for both endonuclease and methyltransferase
      functions while B recognizes the DNA. Like almost all Type IIB systems, BcgI
      needs two unmethylated sites for nuclease activity; it cuts both sites upstream
      and downstream of the recognition sequence, hydrolyzing eight phosphodiester
      bonds in a single synaptic complex. This complex may incorporate four A(2)B
      protomers to give the eight catalytic centres (one per A subunit) needed to cut
      all eight bonds. The BcgI recognition sequence contains one adenine in each
      strand that can be N(6)-methylated. Although most DNA methyltransferases operate
      at both unmethylated and hemi-methylated sites, BcgI methyltransferase is only
      effective at hemi-methylated sites, where the nuclease component is inactive.
      Unlike the nuclease, the methyltransferase acts at solitary sites, functioning
      catalytically rather than stoichiometrically. Though it transfers one methyl
      group at a time, presumably through a single A subunit, BcgI methyltransferase
      can be activated by adding extra A subunits, either individually or as part of
      A(2)B protomers, which indicates that it requires an assembly containing at least
      two A(2)B units.

PMID- 23147005
TI  - Organization of the BcgI restriction-modification protein for the cleavage of
      eight phosphodiester bonds in DNA.
AB  - Type IIB restriction-modification systems, such as BcgI, feature a single protein
      with both endonuclease and methyltransferase activities. Type IIB nucleases
      require two recognition sites and cut both strands on both sides of their
      unmodified sites. BcgI cuts all eight target phosphodiester bonds before
      dissociation. The BcgI protein contains A and B polypeptides in a 2:1 ratio: A
      has one catalytic centre for each activity; B recognizes the DNA. We show here
      that BcgI is organized as A(2)B protomers, with B at its centre, but that these
      protomers self-associate to assemblies containing several A(2)B units. Moreover,
      like the well known FokI nuclease, BcgI bound to its site has to recruit
      additional protomers before it can cut DNA. DNA-bound BcgI can alternatively be
      activated by excess A subunits, much like the activation of FokI by its catalytic
      domain. Eight A subunits, each with one centre for nuclease activity, are
      presumably needed to cut the eight bonds cleaved by BcgI. Its nuclease reaction
      may thus involve two A(2)B units, each bound to a recognition site, with two more
      A(2)B units bridging the complexes by protein-protein interactions between the
      nuclease domains.

PMID- 23147006
TI  - Graphite furnace atomic absorption spectrophotometry--a novel method to quantify
      blood volume in experimental models of intracerebral hemorrhage.
AB  - Intracerebral hemorrhage (ICH) accounts for 10% of all strokes and has a
      significantly higher mortality than cerebral ischemia. For decades, ICH has been
      neglected by experimental stroke researchers. Recently, however, clinical trials
      on acute blood pressure lowering or hyperacute supplementation of coagulation
      factors in ICH have spurred an interest to also design and improve translational
      animal models of spontaneous and anticoagulant-associated ICH. Hematoma volume is
      a substantial outcome parameter of most experimental ICH studies. We present
      graphite furnace atomic absorption spectrophotometric analysis (AAS) as a
      suitable method to precisely quantify hematoma volumes in rodent models of ICH.

PMID- 23147007
TI  - Improved detection of amnestic MCI by means of discriminative vector quantization
      of single-trial cognitive ERP responses.
AB  - Cognitive event-related potentials (ERPs) are widely employed in the study of
      dementive disorders. The morphology of averaged response is known to be under the
      influence of neurodegenerative processes and exploited for diagnostic purposes.
      This work is built over the idea that there is additional information in the
      dynamics of single-trial responses. We introduce a novel way to detect mild
      cognitive impairment (MCI) from the recordings of auditory ERP responses. Using
      single trial responses from a cohort of 25 amnestic MCI patients and a group of
      age-matched controls, we suggest a descriptor capable of encapsulating single
      trial (ST) response dynamics for the benefit of early diagnosis. A customized
      vector quantization (VQ) scheme is first employed to summarize the overall set of
      ST-responses by means of a small-sized codebook of brain waves that is
      semantically organized. Each ST-response is then treated as a trajectory that can
      be encoded as a sequence of code vectors. A subject's set of responses is
      consequently represented as a histogram of activated code vectors. Discriminating
      MCI patients from healthy controls is based on the deduced response profiles and
      carried out by means of a standard machine learning procedure. The novel response
      representation was found to improve significantly MCI detection with respect to
      the standard alternative representation obtained via ensemble averaging (13% in
      terms of sensitivity and 6% in terms of specificity). Hence, the role of
      cognitive ERPs as biomarker for MCI can be enhanced by adopting the delicate
      description of our VQ scheme.

PMID- 23147008
TI  - Anatomo-clinical atlases correlate clinical data and electrode contact
      coordinates: application to subthalamic deep brain stimulation.
AB  - For patients suffering from Parkinson's disease with severe movement disorders,
      functional surgery may be required when medical therapy is not effective. In Deep
      Brain Stimulation (DBS), electrodes are implanted within the brain to stimulate
      deep structures such as SubThalamic Nucleus (STN). The quality of patient
      surgical outcome is generally related to the accuracy of nucleus targeting during
      surgery. In this paper, we focused on identifying optimum sites for STN DBS by
      studying symptomatic motor improvement along with neuropsychological side
      effects. We described successive steps for constructing digital atlases gathering
      patient's location of electrode contacts automatically segmented from
      postoperative images, and clinical scores. Three motor and five
      neuropsychological scores were included in the study. Correlations with active
      contact locations were carried out using an adapted hierarchical ascendant
      classification. Such analysis enabled the extraction of representative clusters
      to determine the optimum site for therapeutic STN DBS. For each clinical score,
      we built an anatomo-clinical atlas representing its improvement or deterioration
      in relation with the anatomical location of electrodes and from a population of
      implanted patients. To the best of our knowledge, we reported for the first time
      a discrepancy between a very good motor improvement by targeting the postero
      superior region of the STN and an inevitable deterioration of the categorical and
      phonemic fluency in the same region. Such atlases and associated analysis may
      help better understanding of functional mapping in deep structures and may help
      pre-operative decision-making process and especially targeting.

PMID- 23147009
TI  - Trial time warping to discriminate stimulus-related from movement-related neural
      activity.
AB  - In tasks where different sensory, cognitive, and motor events are mixed in a
      sequence it is difficult to determine whether neural activity is related to any
      behavioral parameter. Here, we consider the case in which two alternative trial
      alignment schemes correspond to two different neural representations, one
      stimulus-related and the other movement-related, using both simulations of neural
      activity and real recordings in the medial premotor areas during a multiple
      interval tapping task called synchronization-continuation task (SCT). To discover
      whether neural responses are better aligned to sensory or motor events we
      introduce a family of trial-alignment time-warping functions indexed by a single
      parameter such that when the parameter takes the value 0 the trials are aligned
      to the stimulus and when the parameter takes the value 1 they are aligned to the
      movement. We then characterize neurons by the best-fitting alignment scheme (in
      the sense of maximum likelihood) under the assumption that the correct alignment
      would produce homogeneous trials without excess trial-to-trial variation. We use
      Bayes factors to determine the evidence in favor of sensory or motor neural
      alignments. The simulations revealed that the variability in neural responses and
      sequential motor outputs are key parameters to obtain appropriate warping
      results. In addition, the analysis on the activity of 500 neurons in the medial
      premotor areas of monkeys executing the SCT showed that most of the neural
      responses (54.2%) were aligned to the tapping movements instead of the stimuli
      used to drive the temporal behavior.

PMID- 23147013
TI  - Return-to-play interval after sport-related concussion: background review and
      current issues.

PMID- 23147011
TI  - Perennial questions:  on fatigue, on iron, and on anemia.

PMID- 23147014
TI  - Case report:  lower extremity deep vein thrombosis following an intense calf
      workout.
AB  - We report a case of a high-performance athlete with hemoglobin SC who presented
      with asymmetric calf soreness after an intense calf workout. By ultrasonography,
      he was diagnosed with a deep vein thrombosis (DVT) of his right calf.
      Subsequently he presented with a number of sequelae of sickle cell disease: acute
      chest syndrome, avascular necrosis of the hips, and chronic kidney disease. The
      case is instructive as an example of DVT after exercise of the lower extremities,
      which has not been documented well. The case also illustrates a number of health
      sequelae of sickle cell disease that mimic more common musculoskeletal
      complaints. Sports medicine providers will have to consider these uncommon but
      profound diagnostic entities when caring for athletes with sickle cell disease.
      The case further highlights how research can inform the clinical decisions and
      policies aimed at reducing the risk of life-threatening and lifelong sequelae of
      sickle cell disease in athletes.

PMID- 23147015
TI  - Bilateral acute compartment syndrome in a football player:  a case report.

PMID- 23147016
TI  - Common ultramarathon injuries and illnesses:  race day management.
AB  - Participation in ultramarathons has become increasingly popular especially among
      nonelite athletes. Ultramarathons have a wide spectrum of race characteristics
      from the variety of distances to environmental factors. Ultramarathons continue
      to attract a relatively small number of participants who on average are more
      experienced than marathon runners. There are limited epidemiologic studies on
      common ultramarathon injuries and illnesses. Musculoskeletal and dermatologic
      problems are very common among ultramarathoners. Each ultramarathon is unique,
      and medical directors should try to establish an injury surveillance system in
      order to be better prepared for possible medical conditions. The focus of this
      article is on the evaluation and management of common medical conditions
      encountered during ultramarathons.

PMID- 23147017
TI  - Ultrasound in athletes: emerging techniques in point-of-care practice.
AB  - Ultrasound offers sports medicine clinicians the potential to diagnose, treat,
      and manage a broad spectrum of conditions afflicting athletes. This review
      article highlights applications of ultrasound that hold promise as point-of-care
      diagnostics and therapeutic tools that can be used directly by clinicians to
      direct real-time management of athletes. Point-of-care ultrasound has been
      examined most in the context of musculoskeletal disorders in athletes, with
      attention given to Achilles tendinopathy, patellar tendinopathy, hip and thigh
      pathology, elbow tendinopathy, wrist pathology, and shoulder pain. More research
      has focused on therapeutic applications than diagnostic, but initial evidence has
      been generated in both. Preliminary evidence has been published also on abdominal
      ultrasound for splenic enlargement in mononucleosis, cardiopulmonary processes
      and hydration status, deep vein thrombosis, and bone mineral density. Further
      research will be required to validate these applications and to explore further
      applications of portable ultrasound that can be used in the care of athletes.

PMID- 23147018
TI  - Demystifying preventive equipment in the competitive athlete.
AB  - Sports-related injuries are rising as the interest and participation in sports
      rise. Recent epidemiologic study suggested that one in five injuries in
      individuals 18 years or younger reporting to the emergency department were found
      to be sports related. These injuries also were found to account for up to 19% of
      primary care injury-related visits. In this article, we will be reviewing the use
      of five different types of sports protective equipment (ankle support, knee
      support, mouthguards, eyeguards, and helmets) and the protection provided by each
      with level of current evidence. We found that the literature supports the use of
      ankle braces and mouthguards in athletes. The use of knee braces and eye
      protection in some athletes is indicated. Helmets to prevent head injuries are
      supported, but it is uncertain if that extends to concussion prevention. Soccer
      headgear is not supported and needs randomized control studies to show benefit.

PMID- 23147019
TI  - Diabetes in the competitive athlete.
AB  - Diabetes mellitus is the most common group of metabolic diseases and is
      characterized by hyperglycemia resulting from defects in insulin secretion,
      insulin action, or both. Most patients with diabetes are type 2 (90%); the
      remaining patients have type 1 disease. Athletes with diabetes range from the
      athlete participating in various youth sports to the competitive Olympic athlete
      and present a significant challenge to themselves and the medical staff who care
      for them on a daily basis. Each sport and the type of exercise have their own
      effects on diabetes management with numerous factors that significantly affect
      glucose levels, including stress, level of hydration, the rate of glycogenolysis
      and gluconeogenesis, and the secretion of counter-regulatory hormones. This
      article provides a general overview of diabetes mellitus, the effects of exercise
      on glucose levels, and a detailed review of the potential complications
      encountered in the management of diabetes in the athlete.

PMID- 23147020
TI  - Common medical problems of instrumental athletes.
AB  - The fields of sports medicine and performing arts medicine have begun recent
      initiatives to collaborate more closely and to share information pertinent to the
      treatment of athletes and performing artists. This article provides a review of
      the common musculoskeletal and neurological problems encountered among performing
      artists who play instruments. Approaches to history, examination, diagnosis, and
      treatment are offered, based on literature reviews, expert opinion, and the
      authors' own experiences in a musician's clinic. Treatments focus on conservative
      management within a multidisciplinary framework, and indications are given for
      appropriate surgical referral. Providers are encouraged to build an understanding
      of the unique issues affecting instrumental athletes.

PMID- 23147021
TI  - Beware the consequences of your imaging.
AB  - Advanced imaging, especially magnetic resonance imaging (MRI), has added to our
      clinical diagnostic capabilities. With this advancement, however, has come the
      added responsibility of determining clinically significant MRI findings from
      "incidental findings" of no clinical relevance. It is most important for the
      clinician to be aware of the occurrence of abnormal findings in asymptomatic
      populations to place the imaging findings in the context of the history and
      physical examination to ensure we "treat the patient, not the imaging."
      Frequently imaged joints are reviewed highlighting these issues.

PMID- 23147022
TI  - Bone health in endurance athletes:  runners, cyclists, and swimmers.
AB  - Weight-bearing exercise has been recognized widely to be beneficial for long-term
      bone health. However inherent differences in bone-loading characteristics and
      energy expenditure during participation in endurance sports place many endurance
      athletes at a relative disadvantage with regard to bone health compared with
      other athletes. Adolescents and adults who participate in endurance sports, such
      as running, and non-weight-bearing sports, such as biking and swimming, often
      have lower bone mineral density (BMD) than athletes participating in ball and
      power sports, and sometimes their BMD is lower than their inactive peers. Low BMD
      increases the risk of stress and fragility fractures, both while an athlete is
      actively competing and later in life. This article reviews the variable effects
      of distance running, cycling, swimming, and triathlons on bone health; the
      evaluation of stress and fragility fractures; and the diagnosis, management, and
      prevention of low BMD in endurance athletes.

PMID- 23147023
TI  - Interventional spine procedures in athletes.
AB  - Back pain is common in athletes and a source of missed time from practice and
      competition. Pain generators include muscle (strain), ligament (myofascial sprain
      and strain), intervertebral disc (herniation and degeneration), nerve
      (radiculopathy), joint (facet and sacroiliac (SI) joint), and bones (pars
      interarticularis defect). The goal of treatment of an athlete with back pain is
      to relieve symptoms and facilitate safe but rapid return to play with no change
      in performance. Initial conservative treatment includes relative rest, anti
      inflammatory medications, and physical therapy. The use of interventional spine
      procedures in athletes with back pain has gained popularity as a nonoperative
      treatment option. Although there is lack of high-quality evidence of these
      procedures specifically in athletes, this article will discuss the utility of
      selective nerve root blocks, epidural steroid injections, intradiscal injections,
      pars interarticularis injection, facet joint interventions (intraarticular
      injection, medial branch block, and radiofrequency neurotomy), and SI joint
      interventions (intraarticular injection and radiofrequency neurotomy).

PMID- 23147024
TI  - Immune-related gene expression in nurse honey bees (Apis mellifera) exposed to
      synthetic acaricides.
AB  - The mite Varroa destructor is an ectoparasite affecting honey bees worldwide.
      Synthetic acaricides have been among the principal tools available to beekeepers
      for its control, although several studies have shown its negative effects on
      honey bee physiology. Recent research suggests that those molecules strongly
      impact on immune signaling cascades and cellular immunity. In the present work,
      LC(50) in six-day-old bees were determined for the following acaricides: tau
      fluvalinate, flumethrin, amitraz and coumaphos. According to this obtained value,
      a group of individuals was treated with each acaricide and then processed for
      qPCR analysis. Transcript levels for genes encoding antimicrobial peptides and
      immune-related proteins were assessed. Flumethrin increased the expression of
      hymenoptaecin when comparing treated and control bees. Significant differences
      were recorded between coumaphos and flumethrin treatments, while the first one
      reduced the expression of hymenoptaecin and abaecin, the last one up-regulated
      their expressions. No significant statistically changes were recorded in the
      expression levels of vitellogenin, lysozyme or glucose dehydrogenase among bees
      treated with acaricides and control bees. This work constitutes the first report,
      under laboratory conditions, about induction of immune related genes in response
      to synthetic miticides.

PMID- 23147025
TI  - Expression patterns and binding properties of three pheromone binding proteins in
      the diamondback moth, Plutella xyllotella.
AB  - Pheromone binding proteins (PBPs) play a key role in transporting hydrophobic sex
      pheromone components emitted by con-specific female across aqueous sensillar
      lymph to the surface of olfactory receptor neurons. A number of PBPs have been
      cloned, however, details of their function are still largely unknown. Here three
      pheromone binding protein genes in the diamondback moth, Plutella xyllotella were
      cloned. The three PxylPBP genes are not only expressed in chemosensory tissues
      but also expressed in female reproductive organs and male legs. To better
      understand the functions of PxylPBPs in the initial steps of pheromone
      recognition, three PxylPBPs were expressed in Escherichia coli and the ligand
      binding specificities of purified recombinant PBPs were investigated.
      Fluorescence binding assays indicate that three PxylPBPs not only robustly bound
      all four sex pheromone components but also significantly bound pheromone analogs
      with at least one double bond, while weakly bound tested plant volatiles.
      Although pheromone analogs bound PBPs, they could not elicit the moth's
      electrophysiological response. These experiments provide evidence that PxylPBPs
      have limited selectivity of pheromone components and analogs and some downstream
      components such as odor receptors might be involved in selectivity and
      specificity of pheromone perception in P. xyllotella.

PMID- 23147026
TI  - Abstracts of the XXIII Annual Meeting of the Pediatrics Endocrinology
      Latinoamerican Society (SLEP). Montevideo, Uruguay. November 20-23, 2012.

PMID- 23147028
TI  - Discoidin domain receptors guide axons along longitudinal tracts in C. elegans.
AB  - Discoidin domain receptors are a family of receptor tyrosine kinases activated by
      collagens. Here we characterize the role of the two discoidin domain receptors,
      ddr-1 and ddr-2, of the nematode C. elegans during nervous system development.
      ddr-2 mutant animals exhibit axon guidance defects in major longitudinal tracts
      most prominently in the ventral nerve cord. ddr-1 mutants show no significant
      phenotype on their own but significantly enhance guidance defects of ddr-2 in
      double mutants. ddr-1 and ddr-2 GFP-reporter constructs are expressed in neurons
      with axons in all affected nerve tracts. DDR-1 and DDR-2 GFP fusion proteins
      localize to axons. DDR-2 is required cell-autonomously in the PVPR neuron for the
      guidance of the PVPR pioneer axon, which establishes the left ventral nerve cord
      tract and serves as substrate for later outgrowing follower axons. Our results
      provide the first insight on discoidin domain receptor function in invertebrates
      and establish a novel role for discoidin domain receptors in axon navigation and
      axon tract formation.

PMID- 23147029
TI  - Learning curve for bipolar transurethral enucleation and resection of the
      prostate in saline for symptomatic benign prostatic hyperplasia: experience in
      the first 100 consecutive patients.
AB  - BACKGROUND: Bipolar transurethral enucleation and resection of the prostate in
      saline has recently been considered as a safe and technically feasible endoscopic
      procedure for symptomatic benign prostatic hyperplasia. However, it has not been
      accepted widely because of the perception of technical difficulty. METHODS: A
      retrospective data review was performed of the first consecutive 100 patients who
      had undergone bipolar transurethral enucleation and resection of prostatic
      adenoma. Operative outcome, complications, ratio of conversion to conventional
      transurethral resection of the prostate and efficiency of tissue enucleation and
      resection were used to assess the learning curve. RESULTS: Bipolar transurethral
      enucleation and resection of the prostate was successfully performed in 83
      patients. The mean operative time was 117.5 min, and the mean indwelling
      catheterization was 3.3 +/- 1.9 days. After 6 months, maximum urinary flow was
      21.34 +/- 4.09 ml/s, IPSS was 9.66 +/- 2.64, and quality of life was 2.31 +/-
      0.92 with a residual prostate volume of 35.29 +/- 17.57 ml. Regarding the
      learning curve, the ratio of conversion to conventional bipolar transurethral
      resection of the prostate decreased after 30 cases, and the efficiency of
      enucleation and resection increased significantly with accumulative experience
      after 50 cases. CONCLUSIONS: The current results established that bipolar
      transurethral enucleation and resection of the prostate in saline is a safe and
      reproducible procedure.

PMID- 23147030
TI  - Transcriptional activation of Reg2 and Reg3beta genes by glucocorticoids and
      interleukin-6 in pancreatic acinar and islet cells.
AB  - Reg family proteins are expressed in the pancreas and involved in pancreatitis
      and islet beta-cell growth. In order to explore transcriptional control, we
      transfected luciferase reporter genes driven by Reg promoters into acinar AR42J
      and islet MIN6 cells. Dexamethasone (DEX) significantly increased the promoter
      expression of Reg2 and Reg3beta genes and the levels of endogenous Reg3beta mRNA
      and protein in AR42J cells. DEX-induced promoter activation was inhibited by the
      inhibitor of poly(ADP-ribose) polymerase, nicotinamide. In MIN6 cells, DEX
      moderately stimulated the transcription of Reg3beta but not Reg2 promoter. While
      IL-6 alone had no effect, coculture with DEX produced a remarkable synergism on
      Reg3beta gene transcription, which was abolished by nicotinamide. Our results
      demonstrated a significant and direct stimulation of Reg2 and Reg3beta genes by
      glucocorticoids, all three were activated in response to inflammation such as in
      pancreatitis. Prominent stimulation of specific Reg genes by glucocorticoids may
      constitute a functional synergism.

PMID- 23147031
TI  - FLAIR with contrast linked to better correlation with stroke symptoms than
      diffision-weighted imaging in a patient: detecting hyperintense acute reperfusion
      injury marker and cortical enhancement.

PMID- 23147032
TI  - Understanding the role of gut microbes and probiotics in obesity: how far are we?
AB  - Obesity has been associated with structural alterations in the gut microbiota,
      suggesting potential causality between specific microbial taxa and this disorder.
      Studies in animal models have also provided evidence for plausible gut microbiota
      mechanisms of action underlying body weight regulation. Yet evidence identifying
      which specific microbes contribute to or predict obesity is not completely
      consistent across studies. More recently, diet has also been shown to be
      primarily involved in regulating the microbiota structure initially related to
      obesity, suggesting that the role of microbes in energy balance is under the
      influence of diet. Controversy over the role of components of the gut microbiota
      in obesity has extended to bacteria, which although weakly related to body weight
      in observational and human intervention studies, are of interest due to their use
      as probiotics. This review focuses exclusively on human observational studies and
      probiotic intervention trials, excluding animal studies and studies in infants at
      early developmental stages, since such results cannot be extrapolated to human
      obesity at later stages in life. In this context, evidence for relationships
      between the gut microbiota composition and obesity and the possible role of
      probiotics is reviewed, discussing the strengths and weaknesses of the studies
      conducted to date.

PMID- 23147033
TI  - The influence of diet on the gut microbiota.
AB  - Diet is a major factor driving the composition and metabolism of the colonic
      microbiota. The amount, type and balance of the main dietary macronutrients
      (carbohydrates, proteins and fats) have a great impact on the large intestinal
      microbiota. The human colon contains a dense population of bacterial cells that
      outnumber host cells 10-fold. Bacteroidetes, Firmicutes and Actinobacteria are
      the three major phyla that inhabit the human large intestine and these bacteria
      possess a fascinating array of enzymes that can degrade complex dietary
      substrates. Certain colonic bacteria are able to metabolise a remarkable variety
      of substrates whilst other species carry out more specialised activities,
      including primary degradation of plant cell walls. Microbial metabolism of
      dietary carbohydrates results mainly in the formation of short chain fatty acids
      and gases. The major bacterial fermentation products are acetate, propionate and
      butyrate; and the production of these tends to lower the colonic pH. These weak
      acids influence the microbial composition and directly affect host health, with
      butyrate the preferred energy source for the colonocytes. Certain bacterial
      species in the colon survive by cross-feeding, using either the breakdown
      products of complex carbohydrate degradation or fermentation products such as
      lactic acid for growth. Microbial protein metabolism results in additional
      fermentation products, some of which are potentially harmful to host health. The
      current 'omic era promises rapid progress towards understanding how diet can be
      used to modulate the composition and metabolism of the gut microbiota, allowing
      researchers to provide informed advice, that should improve long-term health
      status.

PMID- 23147034
TI  - Determination of voriconazole in human plasma by HPLC-ESI-MS and application to
      pharmacokinetic study.
AB  - A fast, sensitive, high-performance liquid chromatography-tandem mass
      spectrometry method was developed for the determination of voriconazole in human
      plasma. Carbamazepine was used as the internal standard and the sample
      pretreatment involved one-step protein precipitation. Chromatographic separation
      was conducted on an Ultimate C18 column with a mobile phase consisting of
      acetonitrile-water (containing 0.1% formic acid; 40:60, v/v) at a flow rate of
      0.3 mL/min. The detection of voriconazole was performed on a triple-quadrupole
      tandem mass spectrometer by multiple reaction monitoring with an electrospray
      ionization source in the positive mode. The standard curve was linear (r(2) >=
      0.99) within the concentration range of 2.49-293 ng/mL. The intra-day and inter
      day precision values were below 5.3%, and the accuracy was within -4.3-5.7%. The
      method was applicable to the clinical study of the pharmacokinetics of
      voriconazole in healthy volunteers following oral administration.

PMID- 23147035
TI  - Cholera toxin induces a shift from inactive to active cyclooxygenase 2 in
      alveolar macrophages activated by Mycobacterium bovis BCG.
AB  - Intranasal vaccination stimulates formation of cyclooxygenases (COX) and release
      of prostaglandin E(2) (PGE(2)) by lung cells, including alveolar macrophages.
      PGE(2) plays complex pro- or anti-inflammatory roles in facilitating mucosal
      immune responses, but the relative contributions of COX-1 and COX-2 remain
      unclear. Previously, we found that Mycobacterium bovis BCG, a human tuberculosis
      vaccine, stimulated increased release of PGE(2) by macrophages activated in
      vitro; in contrast, intranasal BCG activated no PGE(2) release in the lungs,
      because COX-1 and COX-2 in alveolar macrophages were subcellularly dissociated
      from the nuclear envelope (NE) and catalytically inactive. This study tested the
      hypothesis that intranasal administration of BCG with cholera toxin (CT), a
      mucosal vaccine component, would shift the inactive, NE-dissociated COX-1/COX-2
      to active, NE-associated forms. The results showed increased PGE(2) release in
      the lungs and NE-associated COX-2 in the majority of COX-2(+) macrophages. These
      COX-2(+) macrophages were the primary source of PGE(2) release in the lungs,
      since there was only slight enhancement of NE-associated COX-1 and there was no
      change in COX-1/COX-2 levels in alveolar epithelial cells following treatment
      with CT and/or BCG. To further understand the effect of CT, we investigated the
      timing of BCG versus CT administration for in vivo and in vitro macrophage
      activations. When CT followed BCG treatment, macrophages in vitro had elevated
      COX-2-mediated PGE(2) release, but macrophages in vivo exhibited less activation
      of NE-associated COX-2. Our results indicate that inclusion of CT in the
      intranasal BCG vaccination enhances COX-2-mediated PGE(2) release by alveolar
      macrophages and further suggest that the effect of CT in vivo is mediated by
      other lung cells.

PMID- 23147036
TI  - Cloning and characterization of rainbow trout interleukin-17A/F2 (IL-17A/F2) and
      IL-17 receptor A: expression during infection and bioactivity of recombinant IL
      17A/F2.
AB  - Lower vertebrates have been found to possess genes that have similar homology to
      both interleukin (IL)-17A and IL-17F, which have been termed IL-17A/F. In fish
      species, several of these genes can be present, but, to date, very little is
      known about their functional activity. This article describes the discovery and
      sequence analysis of a rainbow trout (Oncorhynchus mykiss) IL-17A/F2 molecule and
      an IL-17RA receptor. In addition, the bioactivity of the trout IL-17A/F2 is
      investigated for the first time in any species. The predicted IL-17A/F2 and IL
      17RA proteins consist of 146 and 966 amino acids (aa), respectively, with both
      molecules containing conserved family motifs. Expression analysis revealed high
      constitutive expression of trout IL-17A/F2 in mucosal tissues from healthy fish,
      suggesting a potential role in mucosal immunity. When the modulation of IL-17A/F2
      and IL-17RA in vitro was analyzed, it was observed that the two molecules were
      similarly affected. The expression of IL-17A/F2 was also induced in head kidney
      during bacterial, parasitic, and viral infections, revealing a possible function
      in defense against such pathogens. However, downregulation of IL-17RA was seen in
      some tissues and infections. The recombinant IL-17A/F2 protein was produced in
      Escherichia coli and was found to affect the expression of an antimicrobial
      peptide and the proinflammatory cytokines IL-6 and IL-8 in splenocytes.
      Consistent with mammalian IL-17 homologues, our expression and bioactivity
      results imply that trout IL-17A/F2 plays an important role in promoting
      inflammatory and host innate immune responses directed against different pathogen
      groups.

PMID- 23147037
TI  - RivR is a negative regulator of virulence factor expression in group A
      Streptococcus.
AB  - The bacterial pathogen group A Streptococcus (GAS) causes human diseases ranging
      from self-limiting pharyngitis (also known as strep throat) to severely invasive
      necrotizing fasciitis (also known as the flesh-eating syndrome). To control
      virulence factor expression, GAS utilizes both protein- and RNA-based mechanisms
      of regulation. Here we report that the transcription factor RivR (RofA-like
      protein IV) negatively regulates the abundance of mRNAs encoding the hyaluronic
      acid capsule biosynthesis proteins (hasABC; ~7-fold) and the protein G-related
      alpha(2)-macroglobulin-binding protein (grab; ~29-fold). Our data differ
      significantly from those of a previous study of the RivR regulon. Given that grab
      and hasABC are also negatively regulated by the two-component system CovR/S
      (control of virulence), we tested whether RivR functions through CovR/S. A
      comparison of riv and cov single and double mutant strains showed that RivR
      requires CovR activity for grab and hasABC regulation. Analysis of the upstream
      region of rivR identified a novel promoter the deletion of which reduced rivR
      mRNA abundance by 70%. A rivR mutant strain had a reduced ability to adhere to
      human keratinocytes relative to that of the parental and complemented strains, a
      phenotype that was abolished upon GAS pretreatment with hyaluronidase,
      highlighting the importance of capsule regulation by RivR during colonization.
      The rivR mutant strain was also attenuated for virulence in a murine model of
      bacteremia infection. Thus, we identify RivR as an important regulator of GAS
      virulence and provide new insight into the regulatory networks controlling
      virulence factor production in this pathogen.

PMID- 23147038
TI  - Streptococcus pneumoniae capsular serotype invasiveness correlates with the
      degree of factor H binding and opsonization with C3b/iC3b.
AB  - Different capsular serotypes of Streptococcus pneumoniae vary markedly in their
      ability to cause invasive infection, but the reasons why are not known. As
      immunity to S. pneumoniae infection is highly complement dependent, variations in
      sensitivity to complement between S. pneumoniae capsular serotypes could affect
      invasiveness. We have used 20 capsule-switched variants of strain TIGR4 to
      investigate whether differences in the binding of the alternative pathway
      inhibitor factor H (FH) could be one mechanism causing variations in complement
      resistance and invasive potential between capsular serotypes. Flow cytometry
      assays were used to assess complement factor binding and complement-dependent
      neutrophil association for the TIGR4 capsule-switched strains. FH binding varied
      with the serotype and inversely correlated with the results of factor B binding,
      C3b/iC3b deposition, and neutrophil association. Differences between strains in
      FH binding were lost when assays were repeated with pspC mutant strains, and loss
      of PspC also reduced differences in C3b/iC3b deposition between strains. Median
      FH binding was high in capsule-switched mutant strains expressing more invasive
      serotypes, and a principal component analysis demonstrated a strong correlation
      between serotype invasiveness, high FH binding, and resistance to complement and
      neutrophil association. Further data obtained with 33 clinical strains also
      demonstrated that FH binding negatively correlated with C3b/iC3b deposition and
      that median FH binding was high in strains expressing more invasive serotypes.
      These data suggest that variations in complement resistance between S. pneumoniae
      strains and the association of a serotype with invasiveness could be related to
      capsular serotype effects on FH binding.

PMID- 23147039
TI  - Alveolar epithelial cells are critical in protection of the respiratory tract by
      secretion of factors able to modulate the activity of pulmonary macrophages and
      directly control bacterial growth.
AB  - The respiratory epithelium is a physical and functional barrier actively involved
      in the clearance of environmental agents. The alveolar compartment is lined with
      membranous pneumocytes, known as type I alveolar epithelial cells (AEC I), and
      granular pneumocytes, type II alveolar epithelial cells (AEC II). AEC II are
      responsible for epithelial reparation upon injury and ion transport and are very
      active immunologically, contributing to lung defense by secreting antimicrobial
      factors. AEC II also secrete a broad variety of factors, such as cytokines and
      chemokines, involved in activation and differentiation of immune cells and are
      able to present antigen to specific T cells. Another cell type important in lung
      defense is the pulmonary macrophage (PuM). Considering the architecture of the
      alveoli, a good communication between the external and the internal compartments
      is crucial to mount effective responses. Our hypothesis is that being in the
      interface, AEC may play an important role in transmitting signals from the
      external to the internal compartment and in modulating the activity of PuM. For
      this, we collected supernatants from AEC unstimulated or stimulated in vitro with
      lipopolysaccharide (LPS). These AEC-conditioned media were used in various setups
      to test for the effects on a number of macrophage functions: (i) migration, (ii)
      phagocytosis and intracellular control of bacterial growth, and (iii) phenotypic
      changes and morphology. Finally, we tested the direct effect of AEC-conditioned
      media on bacterial growth. We found that AEC-secreted factors had a dual effect,
      on one hand controlling bacterial growth and on the other hand increasing
      macrophage activity.

PMID- 23147040
TI  - Stereocontrolled synthesis of 4'-C-cyano and 4'-C-cyano-4'-deoxy pyrimidine
      pyranonucleosides as potential chemotherapeutic agents.
AB  - A new series of 4'-C-cyano and 4'-C-cyano-4'-deoxy pyrimidine pyranonucleosides
      has been designed and synthesized. Commercially available 1,2,3,4,6-penta-O
      acetyl-D-mannopyranose (1) was condensed with silylated 5-fluorouracil, uracil,
      and thymine, respectively to afford after deacetylation 1-(alpha-D
      mannopyranosyl)nucleosides (2a-c). Subjecting 2a-c to the sequence of specific
      acetalation, selective protection of the primary hydroxyl group and oxidation,
      the 4'-ketonucleosides 6a-c and 7c were obtained. Reaction of compounds 6a,b, and
      7c with sodium cyanide and subsequent deprotection gave the target 1-(4'-C-cyano
      alpha-D-mannopyranosyl)nucleosides 12a-c. Deoxygenation at the 4'-position of
      cyanohydrins 8a,b, and 11c followed by deprotection led to the desired 1-(4'-C
      cyano-4'-deoxy-alpha-D-talopyranosyl)nucleosides (15a-c). The newly synthesized
      compounds were evaluated for their potential antiviral and cytostatic activities
      in cell culture.

PMID- 23147041
TI  - Milieu dependence of isomeric composition of 1-deoxy-D-erythro-hexo-2,3-diulose
      in aqueous solution determined by high-resolution NMR spectroscopy.
AB  - In this study, high-resolution (1)H (600.03 MHz) and (13)C NMR spectroscopy
      (150.89 MHz) were used to elucidate the structures of the identifiable isomers of
      a complex mixture of equilibrating 1-deoxy-D-erythro-hexo-2,3-diulose (1-DG) (1)
      isomers in aqueous solution. Approximately 15 isomers were formed from the
      investigated deoxy-ketohexose, and the equilibrium of the isomers is dependent on
      the pH values and temperature. In contrast to non-hydrated isomers, hydrated 1-DG
      (1) isomers were exclusively formed in aqueous solution. Their relative
      concentration increased when the pH was increased to more basic conditions. An
      increase in solution temperature led to the elimination of water and an increase
      in the relative concentration of the non-hydrated 1-DG (1) isomers. The observed
      influence of different conditions on the isomeric composition was explained for
      all isomers. Also, these observations provided information for structure
      elucidation. Furthermore, the reaction behaviour of 1-DG (1) under basic
      conditions at high temperatures (up to 347.5K) was interpreted and described.

PMID- 23147042
TI  - Optimised chemical synthesis of 5-substituted UDP-sugars and their evaluation as
      glycosyltransferase inhibitors.
AB  - We have investigated the applicability of different chemical methods for
      pyrophosphate bond formation to the synthesis of 5-substituted UDP-galactose and
      UDP-N-acetylglucosamine derivatives. The use of phosphoromorpholidate chemistry,
      in conjunction with N-methyl imidazolium chloride as the promoter, was identified
      as the most reliable synthetic protocol for the preparation of these non-natural
      sugar-nucleotides. Under these conditions, the primary synthetic targets 5-iodo
      UDP-galactose and 5-iodo UDP-N-acetylglucosamine were consistently obtained in
      isolated yields of 40-43%. Both 5-iodo UDP-sugars were used successfully as
      substrates in the Suzuki-Miyaura cross-coupling with 5-formylthien-2-ylboronic
      acid under aqueous conditions. Importantly, 5-iodo UDP-GlcNAc and 5-(5
      formylthien-2-yl) UDP-GlcNAc showed moderate inhibitory activity against the
      GlcNAc transferase GnT-V, providing the first examples for the inhibition of a
      GlcNAc transferase by a base-modified donor analogue.

PMID- 23147043
TI  - Synthesis of 1,2,3-triazoles from xylosyl and 5-thioxylosyl azides: evaluation of
      the xylose scaffold for the design of potential glycogen phosphorylase
      inhibitors.
AB  - Various acetylenic derivatives and acetylated beta-D-xylopyranosyl azide or the 5
      thio-beta-d-xylopyranosyl analogue were coupled by Cu(I)-catalyzed azide alkyne
      1,3-dipolar cycloaddition (CuAAC) to afford a series of 1-xylosyl-4-substituted
      1,2,3-triazoles. Controlled oxidation of the endocyclic sulfur atom of the 5
      thioxylose moiety led to the corresponding sulfoxides and sulfones. Deacetylation
      afforded 19 hydroxylated xylose and 5-thioxylose derivatives, found to be only
      sparingly water-soluble. Compared to glucose-based analogues, they appeared to be
      much weaker inhibitors of glycogen phosphorylase, as the absence of a
      hydroxymethyl group weakens their binding at the enzyme active site. However,
      such new xylose derivatives might be useful glycomimetics.

PMID- 23147044
TI  - Cardiopulmonary exercise testing: beyond maximal oxygen uptake.

PMID- 23147045
TI  - Muscle strength as a determinant of oxygen uptake efficiency and maximal
      metabolic response in patients with mild-to-moderate COPD.
AB  - OBJECTIVE: To compare the behavior of the oxygen uptake efficiency slope (OUES)
      with that of oxygen uptake at peak exertion (VO2peak). METHODS: This was a
      prospective cross-sectional study involving 21 patients (15 men) with mild-to
      moderate COPD undergoing spirometry, handgrip strength (HGS) testing,
      cardiopulmonary exercise testing, and determination of lactate at peak exertion
      (LACpeak). RESULTS: Mean weight was 66.7 +/- 13.6 kg, and mean age was 60.7 +/-
      7.8 years. With the exception of FEV1 and FEV1/FVC ratio (75.8 +/- 18.6 of
      predicted and 56.6 +/- 8.8, respectively), all spirometric variables were normal,
      as was HGS. The patients exhibited significant metabolic and hemodynamic stress,
      as evidenced by the means (% of predicted) for VO2peak (93.1 +/- 15.4), maximum
      HR (92.5 +/- 10.4), and OUES (99.4 +/- 24.4), as well as for the gas exchange
      rate (1.2 +/- 0.1). The correlation between VO2peak and OUES was significant (r =
      0.747; p < 0.0001). The correlation between HGS and VO2peak (r = 0.734; p <
      0.0001) was more significant than was that between HGS and OUES (r = 0.453; p <
      0.05). Similar results were found regarding the correlations of VO2peak and OUES
      with MIP. Although LACpeak correlated significantly with VO2peak (r = -0.731; p <
      0.0001), only LACpeak/maximum power correlated significantly with OUES (r = 
      0.605; p = 0.004). CONCLUSIONS: Our findings suggest that, in mild-to-moderate
      COPD, VO2 determinants other than overall muscle strength have a greater impact
      on OUES than on VO2peak.

PMID- 23147046
TI  - Prevalence and duration of social security benefits allowed to workers with
      asthma in Brazil in 2008.
AB  - OBJECTIVE: To determine the prevalence and duration of social security benefits
      (SSBs) claims to registered workers with asthma in Brazil by the Brazilian
      National Institute of Social Security in 2008. METHODS: This was a retrospective,
      descriptive study, based on information obtained from the Brazilian Unified
      Benefit System database, on the number of SSB claims granted to registered
      workers with asthma in 2008. The reference population was the monthly mean number
      of workers registered in the Brazilian Social Registry Database in 2008. The
      variables studied were type of economic activity, gender, age, and type/duration
      of the SSB claim. The relationship between work and asthma was evaluated by the
      prevalence ratio (PR) between work-related and non-work-related SSB claims for
      asthma. RESULTS: In 2008, 2,483 SSB claims were granted for asthma, with a
      prevalence of 7.5 allowances per 100,000 registered workers. The prevalence was
      higher among females than among males (PR = 2.1 between the sexes). Workers > 40
      years of age were 2.5 times more likely to be granted an SSB claim for asthma
      than were younger workers. The prevalence was highest among workers engaged in
      the following types of economic activity: sewage, wood and wood product
      manufacturing, and furniture manufacturing (78.8, 22.4, and 22.2 claims/100,000
      registered workers, respectively). The median (interquartile range) duration of
      SSB claims for asthma was 49 (28-87) days. CONCLUSIONS: Asthma is a major cause
      of sick leave, and its etiology has a strong occupational component. This has a
      major impact on employers, employees, and the social security system. Being
      female, being > 40 years of age, and working in the areas of urban
      sanitation/sewage, wood and wood product manufacturing, and furniture
      manufacturing increase the chance of sick leave due to asthma.

PMID- 23147047
TI  - Analysis and validation of probabilistic models for predicting malignancy in
      solitary pulmonary nodules in a population in Brazil.
AB  - OBJECTIVE: To analyze clinical and radiographic findings that influence the
      pathological diagnosis of solitary pulmonary nodule (SPN) and to compare/validate
      two probabilistic models for predicting SPN malignancy in patients with SPN in
      Brazil. METHODS: This was a retrospective study involving 110 patients diagnosed
      with SPN and submitted to resection of SPN at a tertiary hospital between 2000
      and 2009. The clinical characteristics studied were gender, age, presence of
      systemic comorbidities, history of malignancy prior to the diagnosis of SPN,
      histopathological diagnosis of SPN, smoking status, smoking history, and time
      since smoking cessation. The radiological characteristics studied, in relation to
      the SPN, were presence of spiculated margins, maximum transverse diameter, and
      anatomical location. Two mathematical models, created in 1997 and 2007,
      respectively, were used in order to determine the probability of SPN malignancy.
      RESULTS: We found that SPN malignancy was significantly associated with age (p =
      0.006; OR = 5.70 for age > 70 years), spiculated margins (p = 0.001), and maximum
      diameter of SPN (p = 0.001; OR = 2.62 for diameters > 20 mm). The probabilistic
      model created in 1997 proved to be superior to that created in 2007-area under
      the ROC curve (AUC), 0.79 +/- 0.44 (95% CI: 0.70-0.88) vs. 0.69 +/- 0.50 (95% CI:
      0.59-0.79). CONCLUSIONS: Advanced age, greater maximum SPN diameter, and
      spiculated margins were significantly associated with the diagnosis of SPN
      malignancy. Our analysis shows that, although both mathematical models were
      effective in determining SPN malignancy in our population, the 1997 model was
      superior.

PMID- 23147048
TI  - Electric ventilation: indications for and technical aspects of diaphragm pacing
      stimulation surgical implantation.
AB  - OBJECTIVE: Patients with high cervical spinal cord injury are usually dependent
      on mechanical ventilation support, which, albeit life saving, is associated with
      complications and decreased life expectancy because of respiratory infections.
      Diaphragm pacing stimulation (DPS), sometimes referred to as electric
      ventilation, induces inhalation by stimulating the inspiratory muscles. Our
      objective was to highlight the indications for and some aspects of the surgical
      technique employed in the laparoscopic insertion of the DPS electrodes, as well
      as to describe five cases of tetraplegic patients submitted to the technique.
      METHODS: Patient selection involved transcutaneous phrenic nerve studies in order
      to determine whether the phrenic nerves were preserved. The surgical approach was
      traditional laparoscopy, with four ports. The initial step was electrical mapping
      in order to locate the "motor points" (the points at which stimulation would
      cause maximal contraction of the diaphragm). If the diaphragm mapping was
      successful, four electrodes were implanted into the abdominal surface of the
      diaphragm, two on each side, to stimulate the branches of the phrenic nerve.
      RESULTS: Of the five patients, three could breathe using DPS alone for more than
      24 h, one could do so for more than 6 h, and one could not do so at all.
      CONCLUSIONS: Although a longer follow-up period is needed in order to reach
      definitive conclusions, the initial results have been promising. At this writing,
      most of our patients have been able to remain ventilator-free for long periods of
      time.

PMID- 23147049
TI  - Quantitative assessment of the intensity of palmar and plantar sweating in
      patients with primary palmoplantar hyperhidrosis.
AB  - OBJECTIVE: To compare individuals with and without hyperhidrosis in terms of the
      intensity of palmar and plantar sweating. METHODS: We selected 50 patients
      clinically diagnosed with palmoplantar hyperhidrosis and 25 normal individuals as
      controls. We quantified sweating using a portable noninvasive electronic device
      that has relative humidity and temperature sensors to measure transepidermal
      water loss. All of the individuals had a body mass index of 20-25 kg/cm2.
      Subjects remained at rest for 20-30 min before the measurements in order to
      reduce external interference. The measurements were carried out in a climate
      controlled environment (21-24oC). Measurements were carried out on the hypothenar
      region on both hands and on the medial plantar region on both feet. RESULTS: In
      the palmoplantar hyperhidrosis group, the mean transepidermal water loss on the
      hands and feet was 133.6 +/- 51.0 g/m2/h and 71.8 +/- 40.3 g/m2/h, respectively,
      compared with 37.9 +/- 18.4 g/m2/h and 27.6 +/- 14.3 g/m2/h, respectively, in the
      control group. The differences between the groups were statistically significant
      (p < 0.001 for hands and feet). CONCLUSIONS: This method proved to be an accurate
      and reliable tool to quantify palmar and plantar sweating when performed by a
      trained and qualified professional.

PMID- 23147050
TI  - Responsiveness of the six-minute step test to a physical training program in
      patients with COPD.
AB  - OBJECTIVE: To evaluate the responsiveness of the six-minute step test (6MST) to
      an aerobic physical training program (PTP) and to determine the efficacy of the
      PTP regarding spirometric variables during the 6MST, as well as physical
      performance, sensation of dyspnea, and SpO2 during the 6MST and the six-minute
      walk test (6MWT), in patients with COPD. METHODS: This was a controlled,
      prospective randomized study involving patients clinically diagnosed with COPD,
      with an FEV1/FVC ratio < 70%, and having been clinically stable in the last two
      months. The patients were randomized to undergo a PTP on a treadmill, three times
      a week, for six weeks (PTP group) or not (control group). Histories were taken
      from all of the patients, who received regular respiratory therapy during the
      study period, undergoing physical examination and spirometry before and after
      bronchodilator use; incremental symptom-limited cardiopulmonary exercise testing;
      the 6MST; and the 6MWT. RESULTS: Of the 36 patients that completed the study, 21
      and 15 were in the PTP and control groups, respectively. In the PTP group, there
      was a significant increase in the number of steps climbed during the 6MST and in
      the six-minute walk distance (in m and % of predicted), as well as a significant
      decrease in the sensation of dyspnea during the 6MWT. CONCLUSIONS: The 6MST
      showed responsiveness to the PTP. However, the 6MWT appears to be more responsive
      to the PTP proposed.

PMID- 23147051
TI  - Maternal malnutrition during lactation in Wistar rats: effects on elastic fibers
      of the extracellular matrix in the trachea of offspring.
AB  - OBJECTIVE: To investigate the effects of maternal protein malnutrition during
      lactation on the elastic fibers in the tracheas of Wistar rat pups. METHODS: At
      delivery, 12 male pups of two Wistar rat dams were equally divided into two
      groups: control, in which the dam received water and standard rat chow ad libitum
      during lactation; and protein-restricted (PR), in which the dam received water ad
      libitum and an isoenergetic PR diet (8% protein). At 21 days of age, the pups
      were killed and their tracheas were excised. The elastic fibers were stained with
      Weigert's resorcin-fuchsin (after oxidation) and evaluated under light
      microscopy. Morphometric determinations were performed by stereology, with the
      point-counting method, and expressed as volumetric densities. RESULTS: Elastic
      fibers, most having a longitudinal distribution, were identified beneath the
      tracheal mucosa. In addition, well-defined circular layers of elastic fibers were
      found around the inner and outer surfaces of the cartilaginous ring. There were
      no differences between the groups regarding the organization and distribution of
      the elastic fibers. The volumetric density of the elastic fibers of the pups in
      the control and PR groups was 2.46 +/- 0.99% and 3.25 +/- 1.13%, respectively (p
      < 0.01). CONCLUSIONS: The volumetric density of elastic fibers appears to be
      greater in rat pups breastfed by dams receiving a PR diet than in those breastfed
      by dams receiving a normal diet.

PMID- 23147052
TI  - Proposed short-term model of acute allergic response, without adjuvant use, in
      the lungs of mice.
AB  - OBJECTIVE: To determine whether a short-term protocol using subcutaneous
      sensitization with ovalbumin, without the use of adjuvants, would induce an
      eosinophilic response in the lungs of mice similar to that observed in previous,
      well-established protocols. METHODS: Adult female BALB/c mice were randomized and
      divided into groups according to the number of sensitizations with ovalbumin and
      the number/dosage of intranasal ovalbumin challenges. The short-term protocol (10
      days) consisted of one sensitization with ovalbumin and three ovalbumin
      challenges (100 ug). Total and differential cell counts in BAL fluid, levels of
      eosinophil peroxidase in lung tissue, and histopathological examination of the
      lungs were performed 24 h after the last ovalbumin challenge. RESULTS: No
      significant differences were found among the groups regarding the variables
      studied. The short-term protocol, as well as the other protocols studied, induced
      an eosinophilic response similar to that obtained in the positive control.
      CONCLUSIONS: Subcutaneous sensitization with ovalbumin and without the use of
      adjuvants resulted in a significant allergic response in the lungs of mice, even
      in the short-term protocol group. Our findings suggest that this short-term
      protocol can be used as a first-line pre-clinical test for the study of new
      medications, reducing the costs and observation periods.

PMID- 23147053
TI  - Comparison among parameters of maximal respiratory pressures in healthy subjects.
AB  - OBJECTIVE: To investigate four parameters defining maximal respiratory pressures
      and to evaluate their correlations and agreements among those parameters for the
      determination of MIP and MEP. METHODS: This was a cross-sectional study involving
      49 healthy, well-nourished males and females. The mean age was 23.08 +/- 2.5
      years. Measurements were carried out using a pressure transducer, and the
      estimated values for the parameters peak pressure (Ppeak), plateau pressure
      (Pplateau), mean maximal pressure (Pmean), and pressure according to the area
      (Parea) were determined with an algorithm developed for the study. To
      characterize the study sample, we used descriptive statistics, followed by
      repeated measures ANOVA and Bonferroni post hoc test or by the Friedman test and
      the Wilcoxon post hoc test, as well as by Pearson's or Spearman's correlation
      coefficients, depending on the normality of the data. The agreement between the
      variables was assessed with Bland & Altman plots. RESULTS: There were significant
      differences among all of the parameters studied for MIP (Ppeak = 95.69 +/- 27.89
      cmH2O; Parea = 88.53 +/- 26.45 cmH2O-; Pplateau = 82.48 +/- 25.11 cmH2O-; Pmean =
      89.01 +/- 26.41 cmH2O-; p < 0.05 for all) and for MEP (Ppeak = 109.98 +/- 40.67
      cmH2O; Parea = 103.85 +/- 36.63 cmH2O; Pplateau = 98.93 +/- 32.10 cmH2O; Pmean =
      104.43 +/- 36.74 cmH2O; p < 0.0083 for all). Poor agreement was found among
      almost all of the parameters. Higher pressure values resulted in larger
      differences between the variables. CONCLUSIONS: The maximal respiratory pressure
      parameters evaluated do not seem to be interchangeable, and higher pressure
      values result in larger differences among the parameters.

PMID- 23147054
TI  - Factors associated with complications of community-acquired pneumonia in
      preschool children.
AB  - OBJECTIVE: To identify socioeconomic factors and clinical factors associated with
      the development of complications in preschool children hospitalized with
      community-acquired pneumonia (CAP). METHODS: This was a prospective longitudinal
      study involving children (12-59 months of age) diagnosed with CAP and admitted to
      the pediatric wards of two hospitals in the metropolitan area of Campinas,
      Brazil. Children with cystic fibrosis, heart disease, pulmonary malformations,
      neurological disorders, or genetic diseases were excluded. The diagnosis of CAP
      was based on clinical and radiological findings. Data were collected from the
      medical records and with a semi-structured questionnaire. The subjects were
      divided into two groups (complicated and uncomplicated CAP). Socioeconomic and
      clinical variables were compared, and multivariate logistic regression analysis
      was performed. RESULTS: Of the 63 children included, 29 and 34, respectively,
      presented with uncomplicated and complicated CAP. No statistically significant
      differences were found between the groups regarding age at admission, gestational
      age, birth weight, gender, or socioeconomic variables. Significant differences
      were found between the groups regarding history of pneumonia (p = 0.03), previous
      antibiotic therapy (p = 0.004), time elapsed since the onset of CAP (p = 0.01),
      duration of fever prior to admission (p < 0.001), duration of antibiotic therapy
      (p < 0.001), and length of hospital stay (p < 0.001). In the multivariate
      analysis, only duration of fever prior to admission remained in the model (OR =
      1.97; 95% CI: 1.36-2.84; p < 0.001). CONCLUSIONS: Biological variables,
      especially duration of fever prior to admission, appear to be associated with the
      development of complications in children with CAP.

PMID- 23147055
TI  - Factors associated with pulmonary tuberculosis among patients seeking medical
      attention at referral clinics for tuberculosis.
AB  - OBJECTIVE: The identification of behavioral and clinical factors that are
      associated with pulmonary tuberculosis might improve the detection and treatment
      of the disease, thereby reducing its duration and transmission. Our objective was
      to identify sociodemographic, clinical, and behavioral factors that are
      associated with the diagnosis of pulmonary tuberculosis. METHODS: This was a
      cross-sectional study conducted between April of 2008 and March of 2009 at three
      health care clinics in the city of Fortaleza, Brazil. We selected 233 patients
      older than 14 years of age who spontaneously sought medical attention and
      presented with cough for > 2 weeks. Sociodemographic, clinical, and behavioral
      data were collected. Sputum smear microscopy for AFB and mycobacterial culture
      were also carried out, as were tuberculin skin tests and chest X-rays. The
      patients were divided into two groups (with and without pulmonary tuberculosis).
      The categorical variables were compared by the chi-square test, followed by
      logistic regression analysis when the variables were considered significant.
      RESULTS: The prevalence of pulmonary tuberculosis was 41.2%. The unadjusted OR
      showed that the following variables were statistically significant risk factors
      for pulmonary tuberculosis: fever (OR = 2.39; 95% CI, 1.34-4.30), anorexia (OR =
      3.69; 95% CI, 2.03-6.75), and weight loss (OR = 3.37; 95% CI, 1.76-6.62). In the
      multivariate analysis, only weight loss (OR = 3.31; 95% CI, 1.78-6.14) was
      significantly associated with pulmonary tuberculosis. CONCLUSIONS: In areas with
      a high prevalence of tuberculosis, weight loss could be used as an indicator of
      pulmonary tuberculosis in patients with chronic cough for > 2 weeks.

PMID- 23147056
TI  - Correlation between resistance to pyrazinamide and resistance to other
      antituberculosis drugs in Mycobacterium tuberculosis strains isolated at a
      referral hospital.
AB  - The correlation between resistance to pyrazinamide (PZA) and resistance to other
      first-line antituberculosis drugs was investigated in 395 Mycobacterium
      tuberculosis strains isolated from clinical specimens, representing 14% of the
      overall number of M. tuberculosis isolates obtained between 2003 and 2008 at the
      laboratory of a referral university hospital for tuberculosis. A high correlation
      was found between resistance to PZA and multidrug resistance, as well as between
      PZA resistance and resistance to rifampin, isoniazid, and ethambutol (p < 0.01
      for all). These results highlight the importance of performing PZA susceptibility
      testing prior to the prescription of this drug in order to treat drug-resistant
      and multidrug-resistant tuberculosis.

PMID- 23147057
TI  - Pulmonary research recently published in Brazilian journals.
AB  - We reviewed original articles in the field of pulmonary medicine that had been
      recently published in 12 Brazilian journals--general or specialty journals-
      excluding the Brazilian Journal of Pulmonology. All were journals indexed for the
      Institute for Scientific Information Web of Knowledge. The selection of articles
      was based on the "continuously variable rating" concept. We have organized the
      articles by category.

PMID- 23147058
TI  - Air pollution and the respiratory system.
AB  - Over the past 250 years-since the Industrial Revolution accelerated the process
      of pollutant emission, which, until then, had been limited to the domestic use of
      fuels (mineral and vegetal) and intermittent volcanic emissions-air pollution has
      been present in various scenarios. Today, approximately 50% of the people in the
      world live in cities and urban areas and are exposed to progressively higher
      levels of air pollutants. This is a non-systematic review on the different types
      and sources of air pollutants, as well as on the respiratory effects attributed
      to exposure to such contaminants. Aggravation of the symptoms of disease,
      together with increases in the demand for emergency treatment, the number of
      hospitalizations, and the number of deaths, can be attributed to particulate and
      gaseous pollutants, emitted by various sources. Chronic exposure to air
      pollutants not only causes decompensation of pre-existing diseases but also
      increases the number of new cases of asthma, COPD, and lung cancer, even in rural
      areas. Air pollutants now rival tobacco smoke as the leading risk factor for
      these diseases. We hope that we can impress upon pulmonologists and clinicians
      the relevance of investigating exposure to air pollutants and of recognizing this
      as a risk factor that should be taken into account in the adoption of best
      practices for the control of the acute decompensation of respiratory diseases and
      for maintenance treatment between exacerbations.

PMID- 23147059
TI  - The chest and aging: radiological findings.
AB  - In the elderly (conventionally defined as individuals >= 60 years of age), it is
      often difficult to establish what normality is, because of the numerous
      anatomical and physiological modifications that occur during the aging process.
      As a result, the greatest challenge is to differentiate between the normal aging
      process and the onset of disease. Healthy elderly people commonly present
      borderline findings on chest imaging. We systematically reviewed the medical
      literature on the subject, covering the period between 1950 and 2011, including
      articles in Portuguese, English, French, Italian, and Spanish. We searched the
      PubMed, LILACS, and SciELO databases, using the search terms "age", "aging",
      "lung", "thorax", "chest", "X-ray", "radiography", "pulmonary", and "computed
      tomography"-as well as their corresponding translations-in various combinations.
      We included only original or review articles on aging-related chest imaging
      findings. In broad terms, aging results in physiological modifications that must
      be recognized so as not to be erroneously interpreted as pathological.

PMID- 23147060
TI  - Hemophagocytic syndrome due to pulmonary sarcoidosis.
AB  - Although hemophagocytic syndrome is a rare clinical condition, it is associated
      with high mortality and the number of cases described in the literature has
      progressively increased. The diagnosis of hemophagocytic syndrome is made on the
      basis of a finding of hemophagocytosis. Sarcoidosis is a highly prevalent disease
      whose course and prognosis might correlate with the initial clinical presentation
      and the extent of the disease. We report the case of a patient with long-standing
      sarcoidosis who presented with intermittent fever and fatigue. The diagnosis of
      hemophagocytic syndrome was made by bone marrow aspiration, and specific
      treatment was ineffective. This is the third case of sarcoidosis-related
      hemophagocytic syndrome reported in the literature and the first reported in
      Latin America. All three cases had unfavorable outcomes.

PMID- 23147061
TI  - Tailored intracuff pressures.

PMID- 23147062
TI  - Osteitis in a female infant after vaccination with BCG Moreau in the neonatal
      period.

PMID- 23147063
TI  - Noninvasive mechanical ventilation in a patient with acute pancreatitis and
      respiratory failure.

PMID- 23147064
TI  - Urine in the pleural cavity: an unexpected finding.

PMID- 23147066
TI  - Recent developments of ketene dithioacetal chemistry.
AB  - Ketene dithioacetals are versatile intermediates in organic synthesis. Extensive
      research, since the last decade, has given rise to new prospects in their
      chemistry. The objective of this review is twofold: first, to highlight the new
      prospects in the chemistry of functionalized ketene dithioacetals, and second, to
      provide an intrinsic link between ketene dithioacetal groups and a variety of
      other functional groups, which has brought out many new facts that will assist in
      future designs.

PMID- 23147065
TI  - Structural basis of single molecular heparin-FX06 interaction revealed by SPM
      measurements and molecular simulations.
AB  - Heparin, a functionalized polysaccharide, is observed under a scanning tunneling
      microscope, which shows atomic scale conformational details. The peptide FX06 is
      found to bind to five consecutive sugar units of heparin and this interaction is
      directly revealed by atomic force microscopy and dynamic force spectroscopy
      measurements. The determined free energy change agrees well with the dynamic
      calculation result.

PMID- 23147068
TI  - Prostate Cancer and Prostatic Diseases (2012) 15, 313.

PMID- 23147067
TI  - Nutrient-based therapies for bipolar disorder: a systematic review.
AB  - BACKGROUND: Pharmacotherapy is the first line of treatment for bipolar disorder,
      but many patients continue to experience persistent subthreshold symptoms.
      Alternative adjunct treatments, including nutritional therapies, may have the
      potential to alleviate residual symptoms and improve the outcomes of standard
      pharmacotherapy. The aim of this paper is to critically review the current
      clinical evidence and mechanisms of action of nutrient-based therapies alone or
      in combination with commonly used pharmacotherapies for mania and bipolar
      depression. METHODS: We conducted a Medline search for clinical trials conducted
      with humans, published in English from 1960 to 2012 using nutritional supplements
      such as n-3, chromium, inositol, choline, magnesium, folate and tryptophan alone
      or in combination with pharmacotherapies for the treatment of bipolar disorder.
      RESULTS: Preliminary data yields conflicting but mainly positive evidence for the
      use of n-3 fatty acids and chromium in the treatment of bipolar depression.
      Limited evidence found that inositol may be helpful for bipolar depression, but
      larger sample sizes are needed. Preliminary randomized, controlled trials suggest
      that choline, magnesium, folate and tryptophan may be beneficial for reducing
      symptoms of mania. CONCLUSIONS: Given the potential public health impact of
      identifying adjunct treatments that improve psychiatric as well as physical
      health outcomes, nutritional treatments appear promising for the management of
      bipolar disorder but require further study.

PMID- 23147069
TI  - Passive circulating cell sorting by deformability using a microfluidic gradual
      filter.
AB  - The deformability of circulating leukocytes plays an important role in the
      physiopathology of several diseases like sepsis or acute respiratory distress
      syndrome (ARDS). We present here a microfluidic method for the passive testing,
      sorting and separating of non-adherent cell populations by deformability. It
      consists of microfluidic sieves in series with pore sizes decreasing from the
      upstream to the downstream. The method capabilities are demonstrated with
      monocytic cell lines (THP-1) treated by Jasplakinolide (a stabilizer of
      polymerized actin), LatrunculinA (an inhibitor of actin polymerization), and with
      the plasma of patients suffering from ARDS. Simple sample injection with standard
      syringes and pumps makes the method readily adapted for experimentation in
      hospitals.

PMID- 23147070
TI  - Foreword.

PMID- 23147071
TI  - The development of myelin repair agents for treatment of multiple sclerosis:
      progress and challenges.
AB  - Multiple Sclerosis (MS) is an inflammatory demyelinating disorder which affects
      the central nervous system. Multiple sclerosis treatment has traditionally
      focused on preventing inflammatory damage to the myelin sheath. Indeed, all
      currently available disease modifying agents are immunomodulators. However, the
      limitations of this approach are becoming increasingly clear, leading to the
      exploration of other potential therapeutic strategies. In particular, targeting
      the endogenous remyelination system to promote replacement of the lost myelin
      sheath has shown much promise. As our understanding of remyelination biology
      advances, the realization of a remyelinating therapeutic comes closer to
      fruition. In our review, we aim to summarize the limitations of the current
      immune focused treatment strategy and discuss the potential of remyelination as a
      new treatment method. Finally, we aim to highlight the challenges in the
      identification and development of such therapeutics.

PMID- 23147072
TI  - Frequency and clinical association of Panton-Valentine leukocidin-positive
      Staphylococcus aureus isolates: a study from Kuwait.
AB  - OBJECTIVE: This study was undertaken to determine the frequency of Panton
      Valentine leukocidin (PVL)-producing Staphylococcus aureus among strains isolated
      in our laboratory and to study the association of PVL-positive strains with
      clinical disease. MATERIALS AND METHODS: A total of 291 S. aureus isolates
      obtained from different clinical specimens from June 1, 2009, to March 31, 2010,
      at the Farwania Hospital Laboratory were investigated for antimicrobial
      susceptibility, carriage of genes for PVL, and SCCmec elements. Antimicrobial
      susceptibility testing was performed by standard methods. The presence of mecA
      genes for PVL SCCmec typing was determined by PCR. RESULTS: Of the 291 S. aureus
      isolates, 89 (30.6%) were methicillin-resistant S. aureus (MRSA), whereas 202
      (69.4%) were methicillin susceptible (MSSA). Genes for PVL were detected in 13
      (14.6%) and 24 (12.0%) of the MRSA and MSSA isolates, respectively. The majority
      of the PVL-producing MRSA and MSSA were isolated from 12 (30.7%) and 19 (21.8%)
      cases of skin and soft tissue infections (SSTI), respectively. Although both MSSA
      and MRSA strains were uniformly susceptible to rifampicin, teicoplanin, and
      vancomycin, multidrug resistance was observed among PVL-producing and
      nonproducing MRSA isolates. Both MRSA types carried SCCmec type III, IV, IVc, and
      V genetic elements. CONCLUSION: This study revealed the presence of genes for PVL
      in both MSSA and MRSA, associated mostly with SSTI and respiratory tract
      infections, supporting previous observations that PVL production is widespread
      among S. aureus strains obtained from different clinical sources.

PMID- 23147074
TI  - Design, synthesis and antimicrobial evaluation of novel 1-benzyl 2-butyl-4
      chloroimidazole embodied 4-azafluorenones via molecular hybridization approach.
AB  - A series of novel 1-benzyl-2-butyl-4-chloroimidazole embodied 4-azafluorenone
      hybrids, designed via molecular hybridization approach, were synthesized in very
      good yields using one pot condensation of 1-benzyl-2-butyl-4-chloroimidazole-5
      carboxaldehyde, 1,3-indanedione, aryl/heteroaryl methyl ketones and ammonium
      acetate. All the synthetic derivatives were fully characterized by spectral data
      and evaluated for antimicrobial activity by disc diffusion method against
      selected bacteria and fungal strains. Among the 15 new compounds screened, 4-(1
      benzyl-2-butyl-4-chloro-1H-imidazol-5-yl)-2-(furan-2-yl)-5H-indeno[1,2-b]pyridin
      5-one(10k) has pronounced activity with higher zone of inhibition (ZoI) against
      Staphylococcus aureus, Pseudomonas aeruginosa, Klebsiella pneumoniae, Aspergillus
      flavus and Candida albicans. Also 4-(1-benzyl-2-butyl-4-chloro-1H-imidazol-5-yl)
      2-(dibenzo[b,d]thiophen-2-yl)-5H-indeno [1,2-b]pyridin-5-one (10n) and 4-(1
      benzyl-2-butyl-4-chloro-1H-imidazol-5-yl)-2-(3-tosyl-3H-inden-1-yl)-5H-indeno[1,2
      b]pyridin-5-one (10o) showed selective higher inhibitory activity against
      Aspergillus flavus and Candida albicans. The results demonstrated potential
      importance of molecular hybridization in the development of 10k as potential
      antimicrobial agent.

PMID- 23147073
TI  - Effects of AA amyloidosis on survival in peritoneal dialysis.
AB  - BACKGROUND: To investigate the effects of ESRD etiologies on mortality in
      peritoneal dialysis patients. METHODS: We included patients who initiated therapy
      between 2001-2011 and classified them according to etiologies including
      amyloidosis, diabetes mellitus, chronic glomerulonephritis and polycistic renal
      disease. Socio-demographic data, clinical courses and infectious complications
      were compared between groups, and the reasons for peritoneal dialysis withdrawal
      were recorded. Patient and technique survival analysis were performed. RESULTS:
      354 patients were included to the study. Thereafter, 154 patients were excluded.
      Totally, 29 patients with AA-amyloidosis (mean age 37.9+/-16.4 years, follow-up
      time 21.7+/-20.2 months), 78 patients with diabetes mellitus (mean age 56.9+/
      13.6 years, follow-up time 35+/-28.6 months), 68 patients with chronic
      glomerulonephritis (mean age 37.2+/-12 years, follow-up time 47.7+/-29.9 months),
      29 patients with polycystic renal disease (mean age 35.6+/-13.8 years, follow-up
      time 45.4+/-36.8 months) were evaluated. Albumin level was lower in patients with
      amyloidosis at initiation and the end of study (for both p<0.001). Incidence of
      peritonitis and catheter exit site/tunnel infection attacks were higher in
      patients with amyloidosis (p=0.002 and 0.018 respectively). There was statistical
      difference among groups with respect to the last status of patients (p<0.001).
      Deaths were frequent in amyloidotic and diabetic patients. The majority of deaths
      were due to peritonitis and/or sepsis and, cardiovascular reasons. The mortality
      rate was found higher in patients with amyloidosis (log rank=0.005), especially
      at first 2-3 years. Presence of anyone helping to administer peritoneal dialysis
      (OR:6.244, p=0,025), initial serum albumin level (OR:0.352, p=0,034) and presence
      of catheter exit site/tunnel infection(OR:0.250, p=0,015) were independent
      predictors of patient survival. CONCLUSION: Renal failure etiology has effects on
      peritoneal dialysis patients' survival. Patients with amyloidosis have the worst
      survival. Because of loss of PD survival advantage seen in first years of therapy
      in patients with amyloidosis, peritoneal dialysis may not be suitable as first
      choice therapy in this group.

PMID- 23147075
TI  - Identification of novel mPGES-1 inhibitors through screening of a chemical
      library.
AB  - Human microsomal prostaglandin E synthase-1 (mPGES-1) is an emerging drug target
      for inflammatory disorders and cancer suppression. Therefore, it is crucially
      important to discover mPGES-1 inhibitors with novel structural scaffolds for the
      development of anti-inflammatory drugs. Here, we report the mPGES-1 inhibitors
      identified through screening of a chemical library. Initial screening of 1841
      compounds out of 200,000 in a master library resulted in 9 primary hits. From the
      master library, 387 compounds that share the scaffold structure with the 9
      primary hit compounds were selected, of which 3 compounds showed strong
      inhibitory activity against mPGES-1 having IC(50) values of 1-3 MUM. Notably, a
      derivative of sulfonylhydrazide, compound 3b, inhibited the LPS-induced PGE(2)
      production in RAW 264.7 cells. This compound showed novel scaffold structure
      compared to the known inhibitors of mPGES-1, suggesting that it could be further
      developed as a potent mPGES-1 inhibitor.

PMID- 23147076
TI  - Structure-activity relationships of 2-arylamido-5,7-dihydro-4H-thieno[2,3-c]pyran
      3-carboxamide derivatives as cannabinoid receptor agonists and their analgesic
      action.
AB  - SAR studies were performed on a series of 2-arylamido-5,7-dihydro-4H-thieno[2,3
      c]pyran-3-carboxamide derivatives as cannabinoid receptor agonists. Starting from
      a HTS hit both potency and selectivity could be improved. Modifications to the
      thiophene fusion and C-3 amides were studied. A representative compound 3t
      produced analgesia when dosed orally in inflammatory pain models of writhing and
      carrageenan-induced allodynia.

PMID- 23147077
TI  - Design and biological evaluation of imidazo[1,2-a]pyridines as novel and potent
      ASK1 inhibitors.
AB  - Imidazo[1,2-a]pyridine derivatives were designed, synthesized, and evaluated as
      inhibitors of the apoptosis signal-regulating kinase 1 (ASK1). These were based
      on a benzothiazole derivative that was discovered from high-throughput screening
      of our compound library. As a result, we identified potent, selective, and orally
      bioavailable ASK1 inhibitors for wide range of therapeutic targets.

PMID- 23147079
TI  - Resistin--a novel feature in the diagnosis of sepsis in premature neonates.
AB  - OBJECTIVE: To evaluate the diagnostic potential of resistin in sepsis and to
      compare results with C-reactive protein (CRP) in infants < 32 weeks of gestation.
      STUDY DESIGN: A total of 64 infants were prospectively included in the study.
      Blood samples were collected for basal CRP and resistin within the first hour of
      life. When sepsis was suspected, samples were collected for CRP and resistin
      before the treatment was started (pretreatment CRP and resistin). On the third
      day of sepsis, CRP and resistin levels were measured for evaluating the treatment
      response (follow-up CRP and follow-up resistin). Culture-proven septic patients
      were divided into groups according to early or late-onset sepsis (EOS and LOS)
      and gram-negative or gram-positive sepsis (GNS and GPS). RESULTS: Pretreatment
      and follow-up resistin levels were significantly higher than basal resistin
      levels in both EOS and LOS groups (p < 0.01), with a positive correlation with
      CRP levels. To predict the GNS and GPS area under curve, values of pretreatment
      CRP and resistin were 0.714 and 0.984, respectively (p = 0.039). CONCLUSION:
      Resistin had a superior potential to that of CRP in the diagnosis of sepsis in
      preterm infants. Resistin may be used as an early marker for sepsis in premature
      infants.

PMID- 23147080
TI  - Higher altitude and risk of bronchopulmonary dysplasia among preterm infants.
AB  - OBJECTIVE: To assess the association between altitudes of neonatal intensive care
      units (NICU) and the rate of bronchopulmonary dysplasia (BPD) and BPD/death in
      very preterm infants. STUDY DESIGN: Data from infants born at <33 weeks'
      gestation admitted to Canadian Neonatal Network during 2008 and 2009 were
      analyzed. The associations between the altitude of NICU and the BPD and altitude
      and BPD/death were determined using logistic regression models. RESULTS: Of 7551
      eligible infants, 1540 (20%) were admitted to NICUs at an altitude > 400 m, 3661
      (48%) between 86 and 400 m, 2350 (31%) at <=85 m. The incidences of BPD (21.7%
      versus 17.2%) and BPD/death (26.2% versus 23.0%) were significantly higher in the
      infants admitted to NICUs at >400 m altitude versus those <=400 m altitude (p <
      0.01). In multivariable analyses, the adjusted odds ratio was 1.81 (95%
      confidence interval [CI] 1.05 to 3.12) for BPD and 1.79 (95% CI 1.12 to 2.85) for
      BPD/death among infants admitted to NICUs at altitude > 400 m compared with NICUs
      at altitude <= 400 m. For each 100-m increase in altitude, the odds increased by
      8% for BPD (95% CI 4 to 13%) and 9% for BPD/death (95% CI 5 to 13%); however, the
      increase was mainly due to increase in BPD. CONCLUSION: For very preterm infants,
      higher altitude of NICUs increased the risk of BPD.

PMID- 23147081
TI  - Is it justified to include urine cultures in early (< 72 hours) neonatal sepsis
      evaluations of term and late preterm infants?
AB  - OBJECTIVE: Evaluate the need for urine culture in early neonatal sepsis workup of
      term and late preterm infants. STUDY DESIGN: Urine culture by suprapubic
      aspiration or catheter was included in early sepsis evaluations of 173 term and
      late preterm newborns (mean gestational age 38.6 +/- 2.0 weeks) during a 6-month
      study period. A historic control group included 182 newborns (38.6 +/- 2.9 weeks)
      who had sepsis evaluations without routine urine cultures a year earlier.
      RESULTS: Urine cultures were sampled in 106 (61%) of the study group, No
      significant differences were found between study and control groups in the rate
      of bacteremia (1.73% versus 2.2%) or urinary tract infection (UTI; 0.94% versus
      1.1%), which was low. Early UTIs were not accompanied by bacteremia or structural
      anomalies and were associated with exacerbation of neonatal jaundice in two of
      three infants. CONCLUSIONS: There seems to be no justification for routine urine
      culture in early neonatal sepsis workup of term and late preterm infants, unless
      there are accompanying clinical symptoms, usually related to neonatal jaundice.

PMID- 23147082
TI  - Effects of indomethacin on patent ductus arteriosus in neonates with genetic
      disorders and/or congenital anomalies.
AB  - OBJECTIVES: The study aimed to evaluate the effectiveness of intravenous
      indomethacin (IND) therapy for patent ductus arteriosus (PDA) in neonates with
      genetic disorders and/or congenital anomalies soon after birth. STUDY DESIGN: A
      total of 301 neonates with a genetic disorder and/or congenital anomalies and
      with a gestational age of >= 35 weeks were admitted during the study period.
      Eighty-five neonates with 56 genetic disorders (30 cases of trisomy 21, 10 cases
      of trisomy 18, and 16 others) and 29 congenital anomalies, and with clinical
      symptoms received intravenous IND therapy. The management methods were similar to
      those used for PDA in low-birth-weight infants. RESULTS: IND therapy had a
      clinical benefit at a high rate of 79% in these patients (90% and 70% in neonates
      with trisomies 21 and 18, respectively), including complete closure of the PDA in
      52% of the patients. Although oliguria was observed in 43 infants (51%) and
      slight gastrointestinal bleeding was observed in 12 (14%), no infants had severe
      complications such as intracranial bleeding. CONCLUSIONS: IND therapy is an
      effective treatment option before considering surgery for PDA in neonates with
      genetic disorders and/or congenital anomalies. This therapy may reduce the
      difficulty of treatment in the acute stage among these neonates.

PMID- 23147083
TI  - Further evidence of no association between spinal muscular atrophy and increased
      nuchal translucency.
AB  - INTRODUCTION: Several authors have reported on pregnancy outcomes associated with
      enlarged nuchal translucency (NT) in cases of spinal muscular atrophy (SMA), and
      thus, thickened NT has been considered a possible early ultrasound scan sign of
      SMA. The purpose of our study was to evaluate the association between an
      increased NT and SMA in order to use an ultrasound scan of NT as a possible
      marker of this disorder. MATERIAL AND METHODS: This is a retrospective and
      observational study of women who had a fetus or delivered a baby with SMA
      following a pregnancy in which NT ultrasound has been performed. With the support
      of 'Famiglie SMA', we acquired copies of ultrasound NT measurements, molecular
      genetic tests confirming the SMA diagnosis in the fetus/baby, other prenatal
      ultrasound evaluations and informed consent. RESULTS: Twenty-nine Italian women
      met the inclusion criteria and sent us the requested reports. All had a normal NT
      measurement for the SMA-affected fetus, with a mean of 1.8 mm (range 0.9-2.4).
      DISCUSSION: This series does not confirm an association between increased NT and
      SMA. Fetal genetic testing for the survival motor neuron gene 1 on the basis of
      increased NT is not indicated in couples with no previous history of this genetic
      condition.

PMID- 23147078
TI  - Customized versus population approach for evaluation of fetal overgrowth.
AB  - OBJECTIVE: To compare the ability of customized versus normalized population
      fetal growth norms in identifying neonates at risk for adverse perinatal outcomes
      (APOs) associated with fetal overgrowth and gestational diabetes (GDM). STUDY
      DESIGN: Secondary analysis of a multicenter treatment trial of mild GDM. The
      primary outcome was a composite of neonatal outcomes associated with fetal
      overgrowth and GDM. Birth weight percentiles were calculated using ethnicity- and
      gender-specific population and customized norms (Gardosi). RESULTS: Two hundred
      three (9.8%) and 288 (13.8%) neonates were large for gestational age by
      population (LGApop) and customized (LGAcust) norms, respectively. Both LGApop and
      LGAcust were associated with the primary outcome and neonatal hyperinsulinemia,
      but neither was associated with hypoglycemia or hyperbilirubinemia. The ability
      of customized and population birth weight percentiles for predicting APOs were
      poor (area under the receiver operating characteristic curve < 0.6 for six of
      eight APOs). CONCLUSION: Neither customized nor normalized population norms
      better identify neonates at risk of APOs related to fetal overgrowth and GDM.

PMID- 23147084
TI  - Beneficial aspects of real time flow measurements for the management of acute
      right ventricular heart failure following continuous flow ventricular assist
      device implantation.
AB  - BACKGROUND: Optimal management of acute right heart failure following the
      implantation of a left ventricular assist device requires a reliable estimation
      of left ventricular preload and contractility. This is possible by real-time pump
      blood flow measurements. CLINICAL CASE: We performed implantation of a continuous
      flow left ventricular assist device in a 66 years old female patient with an end
      stage heart failure on the grounds of a dilated cardiomyopathy. Real-time pump
      blood flow was directly measured by an ultrasonic flow probe placed around the
      outflow graft. DIAGNOSIS: The progressive decline of real time flow and the loss
      of pulsatility were associated with an increase of central venous pressure,
      inotropic therapy and progressive renal failure suggesting the presence of an
      acute right heart failure. Diagnosis was validated by echocardiography and
      thermodilution measurements. TREATMENT: Temporary mechanical circulatory support
      of the right ventricle was successfully performed. Real time flow measurement
      proved to be a useful tool for the diagnosis and ultimately for the management of
      right heart failure including the weaning from extracorporeal membrane
      oxygenation.

PMID- 23147086
TI  - A large cryogenic magnetocaloric effect exhibited at low field by a 3D
      ferromagnetically coupled Mn(II)-Gd(III) framework material.
AB  - The large cryogenic magnetocaloric effect of a 3D oxydiacetate-bridged gadolinium
      manganese MOF material, [Mn(H(2)O)(6)][MnGd(oda)(3)](2).6H(2)O (1), was evaluated
      by magnetization and heat capacity measurements. A maximum -DeltaS(m) of 50.1 J
      kg(-1) K(-1) for DeltaH = 70 kG along with significant entropy change at lower
      field was found on account of the weak Mn...Gd ferromagnetic interactions and the
      small molecular mass. This suggests that 1 could be considered as a potential
      coolant for liquid helium temperature applications.

PMID- 23147085
TI  - Multicentre study of circumferential margin positivity and outcomes following
      abdominoperineal excision for rectal cancer.
AB  - BACKGROUND: Rectal cancer outcomes following abdominoperineal excision (APE) have
      been inferior to those for anterior resection, including more positive
      circumferential resection margins (CRMs). An erroneously conservative
      interpretation of APE (rather than a radical resection termed 'extralevator') has
      been proposed as the cause. In this multicentre study, factors contributing to
      CRM positivity were examined following APE according to its original description.
      METHODS: Data were collected from five hospital databases up to June 2011
      including small- and larger-volume units (3 hospitals had 5 or fewer and 2
      hospitals had more than 5 APE procedures per year). Primary outcome measures were
      CRM status; secondary outcomes were local recurrence and death. RESULTS: Of 327
      patients, 302 patients had complete data for analysis. Some 50.0 per cent of
      patients had neoadjuvant chemoradiotherapy. Histopathological examination showed
      that 62.9 per cent had tumour category T3 or T4 cancers, 42.1 per cent had node
      positive disease and the CRM positivity rate was 13.9 per cent. Multivariable
      analysis showed only pathological tumour category pT4 (odds ratio 19.92, 95 per
      cent confidence interval 6.48 to 68.61) and node positivity (odds ratio 3.04,
      1.32 to 8.05) to be risk factors for a positive circumferential margin. CRM
      positivity was a risk factor for local recurrence (P = 0.022) and decreased
      overall survival (P = 0.001). Hospital volume had no impact on the likelihood of
      CRM positivity (P = 0.435). CONCLUSION: In patients undergoing APE by
      appropriately trained surgeons using a standardized approach, margin positivity
      was dictated by tumour stage, but not by centre or surgeon.

PMID- 23147087
TI  - The triathlon.

PMID- 23147088
TI  - Swimming overuse injuries associated with triathlon training.
AB  - Most triathlon overuse injuries occur due to the running and cycling aspects of
      the sport. By nature of swimming being a non-weight-bearing sport, triathletes
      have a tendency to use swimming for rehabilitation and recovery. Swimming has a
      significantly lower injury rate than the other 2 disciplines in a triathlon. Most
      triathletes use the freestyle stroke, because it is typically the first stroke
      learned, it is for many the fastest stroke, and by lifting the head the freestyle
      stroke allows triathletes to sight their direction, which is important in open
      water swimming. During the freestyle stroke, the shoulder undergoes repetitive
      overhead motion, and shoulder pain is the most common and well-documented site of
      musculoskeletal pain in competitive swimmers. It is felt that the pathologic
      process is attributable to repetitive overhead motion causing microtrauma in the
      shoulder from either mechanical impingement or generalized laxity or both.
      Without sufficient rest and recovery, the development of inflammation and pain
      may result. Depending on the age of the triathlete and the exact etiology of the
      shoulder pain, treatment options range from nonsurgical to surgical in nature.

PMID- 23147089
TI  - Chronic musculoskeletal conditions associated with the cycling segment of the
      triathlon; prevention and treatment with an emphasis on proper bicycle fitting.
AB  - Cycling-related injuries account for 20% of all injuries occurring during
      triathlons. Traumatic injuries caused by falls or accidents are thankfully rare
      but can be highly variable and very serious in nature. The best approach to these
      injuries is prevention. The majority of complaints arising from cycling are due
      to overuse or poor technique. The knee joint, lower back, neck, and Achilles
      tendon are the most frequently affected anatomic sites. Anterior knee pain, lower
      back and neck myofascial pain, iliotibial band friction syndrome, and Achilles
      tendonitis are the most common diagnoses. Initial treatment should always use
      rest, ice, compression, and elevation. Muscle strengthening and stretching as
      well as other physical modalities are helpful in the subacute setting. The need
      for surgery is rare. Improper bike fit contributes to the causation of a
      significant number of these conditions. Bike geometry may also be altered to
      alleviate symptoms.

PMID- 23147090
TI  - Triathlon:  running injuries.
AB  - The running portion of the triathlon represents the final leg of the competition
      and, by some reports, the most important part in determining a triathlete's
      overall success. Although most triathletes spend most of their training time on
      cycling, running injuries are the most common injuries encountered. Common causes
      of running injuries include overuse, lack of rest, and activities that aggravate
      biomechanical predisposers of specific injuries. We discuss the running
      associated injuries in the hip, knee, lower leg, ankle, and foot of the
      triathlete, and the causes, presentation, evaluation, and treatment of each.

PMID- 23147091
TI  - Training on a knife's edge: how to balance triathlon training to prevent overuse
      injuries.
AB  - The sport of triathlon offers athletes the chance to build and/or maintain
      cardiovascular fitness across 3 endurance disciplines. Swimming, biking, and
      running each have a host of overuse injuries that can occur as a result of
      overtraining. High running mileage, a history of previous injury, inadequate warm
      up or cool down, and an increase in the years of triathlon experience are a few
      of the factors that have been linked to triathlon overuse injuries. Early
      identification of overtraining symptoms and a corresponding reallocation of
      balance between each discipline, perhaps with an emphasis on increasing swimming,
      may help prevent many overuse injuries.

PMID- 23147092
TI  - Triathlon:  how to mentally prepare for the big race.
AB  - With the mastery of 3 sports required, a triathlon can be a daunting mental
      challenge. Some liken a triathlon to a physical game of chess. A triathlete must
      mentally assess their physical ability across 3 sports against their competitors,
      the environment, and, most of all, themselves. The mental preparation required
      for a triathlon is often minimized, but its importance should not be
      underestimated. Appropriate mental planning should be carried out during
      training. The need for nutrition, race planning, visualization, imaging, and
      possible changes in conditions should all be anticipated. Anxiousness at the
      start of the event is normal, but this energy needs to be channeled
      appropriately, or it can be detrimental. Athletes who arrive at race day with a
      sound mental strategy typically perform better.

PMID- 23147093
TI  - The Hawaiian Ironman-Ma Laila, I Manawa (then and now).

PMID- 23147094
TI  - Training tips for bad weather.
AB  - Competing in triathlons requires a lot of training, often under less than ideal
      conditions. Tips for training in the cold and rain are outlined in this review.

PMID- 23147095
TI  - Strength and conditioning for triathletes.
AB  - Strength exercises for the knee, shoulder, and the core are essential to help
      prevent injuries to triathletes. This article will outline the most common
      exercises to strength the major joints and flexibility exercises to maintain
      range of motion of the joints.

PMID- 23147096
TI  - Masterful care of the aging triathlete.
AB  - Current endurance champions are turning in winning performances in their late 30s
      and 40s. These masters-age athletes present a special challenge to Sport Medicine
      practitioners who in previous decades have simply advised masters-aged athletes
      to stop competing to prevent or treat injury. The fact is, many of the physical
      changes commonly attributed to aging alone are actually due to the rages of
      sedentary aging. Recently a body of literature emerged which begins to define
      what we are capable of with chronic high-level exercise and guides masters-age
      athletes to train and rehab smarter to stay competitive. The factors influencing
      the relative declines in overall performance in the various sports include both
      physiological and lifestyle changes. The following review summarizes age and sex
      related changes in triathlon performance, the biology of aging as it relates to
      endurance sport and factors that affect performance in the masters athletes.

PMID- 23147097
TI  - The triathlon tips from the top:  practical tips for racing and training for a
      triathlon.
AB  - Training for a triathlon is a very demanding pursuit. There are a multitude of
      problems, such as overuse injuries, overtraining, and inappropriate training that
      can derail even the best athlete. We present some of the symptoms to look for to
      avoid overtraining, some training tips to maximize your training time, and look
      at some popular myths that surround endurance training.

PMID- 23147098
TI  - The medical perspective of the Kona Ironman Triathlon.
AB  - The Kona Ironman Triathlon is one of the most difficult endurance races in the
      world. The medical director of this race has summarized his experience in
      managing the injuries that these triathletes suffer. The heat, strong winds, and
      overall length of the event present unique injuries in swimming, cycling, and
      running. These injuries and their management have evolved over the years, and the
      change in their treatment is discussed.

PMID- 23147099
TI  - Hydration-dehydration, heat, humidity, and "cool, clear, water".
AB  - Personal recollections of dehydration meltdowns during the Kona Ironman
      Triathlon, reflections on their cause, and the author's experiential
      recommendations regarding hydration, prevention of dehydration, and "beat the
      heat and humidity" measures.

PMID- 23147102
TI  - Inhibiting accelerated rejection mediated by alloreactive CD4(+) memory T cells
      and prolonging allograft survival by 1alpha,25-dihydroxyvitamin D(3) in nude
      mice.
AB  - Donor-reactive memory T cells are major barriers to long-term survival of
      transplanted organs due to their capacity to accelerate rejection. In this study
      we investigated the ability of 1alpha,25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)]
      to inhibit accelerated rejection mediated by alloreactive CD4(+) memory T cells
      and to prolong cardiac allograft survival in an adoptive T cell memory/heart
      transplant model of nude mice. In vitro, the proliferation of CD4(+) memory T
      cells was significantly inhibited by 1,25(OH)(2)D(3) and was restored following
      addition of exogenous IL-2. Compared with the control group, the mean survival
      time of cardiac allografts in the 1,25(OH)(2)D(3) group was prolonged from 6.5+/
      0.3 to 20.2+/-0.8 days in vivo. Five days after transplantation, the levels of IL
      2 and IFN-gamma were reduced in the grafts and the recipient sera by
      1,25(OH)(2)D(3) treatment, while that of IL-10 increased. The proportions of
      CD4(+) memory T cells and CD4(+)Foxp3(+) T cells, both in recipient spleen and
      lymph nodes, were lowered by 1,25(OH)(2)D(3) treatment when compared with the
      control group. Our data suggests that 1,25(OH)(2)D(3) inhibits expansion of
      CD4(+) memory T cells, possibly by inducing clonal anergy and/or clonal deletion,
      resulting in prolongation of cardiac allograft survival in nude mice. These
      results may provide a rational basis for exploiting 1,25(OH)(2)D(3) as a novel
      immunosuppressant targeting CD4(+) memory T cells.

PMID- 23147103
TI  - A multi-gene phylogeny provides additional insight into the relationships between
      several Ascosphaera species.
AB  - Ascosphaera fungi are highly associated with social and solitary bees, with some
      species being pathogenic to bees (causing chalkbrood) while others are not, and
      proper identification within this genus is important. Unfortunately,
      morphological characterizations can be difficult, and molecular characterizations
      have only used one genetic region. We evaluated multiple phylogenies of the
      Ascosphaera using up to six loci: the Internal Transcribed Spacer (ITS) region,
      18S rRNA, 28S rRNA, Elongation Factor-1alpha (EF-1alpha) the RNA polymerase II
      largest subunit (RPB1), and the second largest subunit (RPB2). The ITS sequence
      alone produced an inadequate phylogeny, and the addition of both the 18S and 28S
      rRNA loci to the ITS sequence produced a phylogeny similar to that based on all
      six genetic regions. For all phylogenies, Ascosphaera torchioi was in a separate
      clade that was the most basal, with a strong genetic similarity to Eremascus
      albus, introducing the possibility of paraphyly within Ascosphaera. Also, based
      on this new phylogeny, we now suggest that the Apis mellifera (honey bee)
      pathogens arose within a group of saprophytes, and the Megachile (leafcutting
      bees) pathogens arose separately.

PMID- 23147104
TI  - Parasitological survey of mangrove oyster, Crassostrea rhizophorae, in the Pacoti
      River Estuary, Ceara State, Brazil.
AB  - The mangrove oyster, Crassostrea rhizophorae (Bivalvia, Ostreidae) is commonly
      collected by fisherwomen in the estuaries of the Ceara State (CE), Northeastern
      Brazil. Despite the socioeconomic importance of this natural resource, there are
      few studies on the health of the oysters in this region. This study aimed to
      survey pathological changes in the mangrove oyster C. rhizophorae in the estuary
      of the Pacoti River, CE. Adult oysters were collected in August 2008 (N=450) and
      December 2009 (N=450) at three sites of the Pacoti estuary and in 2010 (N=600)
      samplings were done quarterly at one site which has showed the higher prevalence
      de Perkinsus. Macroscopical and histological analyses were used to evaluate
      pathological changes, Ray's Fluid Thioglycollate Medium (RFTM) to detect
      Perkinsus spp. and polymerase chain reactions (PCR) and DNA sequencing to
      identify Perkinsus species. In 2009, RFTM assay detected Perkinsus sp. infecting
      the tissues of C. rhizophorae with low prevalences of 1.3%, 6.7% e 7.3% in sites
      1, 2 and 3, respectively, and in 2010, in site 3, prevalence was 2% (12 of 600
      oysters). PCR did not confirm any positive case in 2009 and only 5 in 2010. The
      phylogenetic analyses strongly indicate that the Perkinsus species infecting
      oysters C. rhizophorae of this study belongs to Perkinsus beihaiensis. The
      histology confirmed 11 cases of Perkinsus sp. infecting the C. rhizophorae in
      2009, and only two cases in 2010. Nematopsis sp. was the protozoan observed with
      greater prevalence (up 96.7%). Other found protozoa were: Trichodina,
      Sphenophrya, Ancistrocoma - like and an unknown ovarian parasite. The metazoa
      found were the polychaete Polydora with high prevalences, a turbellarian,
      possibly of the genus Urastoma, an unidentified digenean metacercariae and larvae
      of cestode Tylocephalum. A continuous monitoring of diseases in bivalves from
      this natural population is recommended, since the phylogenetic analyses indicate
      the occurrence of P. beihaiensis infecting oysters C. rhizophorae whose
      pathogenic potential is unknown.

PMID- 23147105
TI  - Cardinium endosymbionts are widespread in synanthropic mite species (Acari:
      Astigmata).
AB  - 'Candidatus Cardinium' is an intracellular endosymbiont or parasite frequently
      occurring in invertebrates including mites and ticks. In this work we report
      Cardinium bacteria in Astigmata mites and explore their incidence in synanthropic
      species. Amplification of a 776 bp bacterial 16S rRNA gene fragment, using
      specific primers, enabled identification of closely related Cardinium sequences
      in 13 laboratory-reared populations of mites. In addition, Cardinium sequences
      were identified in three wild mite populations. Large scale screening of these
      populations showed 100% prevalence of Cardinium, representing the highest
      incidence compared to other major Chelicerate groups.

PMID- 23147106
TI  - Is peak concentration needed in therapeutic drug monitoring of vancomycin? A
      pharmacokinetic-pharmacodynamic analysis in patients with methicillin-resistant
      staphylococcus aureus pneumonia.
AB  - BACKGROUND: We analyzed the pharmacokinetic-pharmacodynamic relationship of
      vancomycin to determine the drug exposure parameters that correlate with the
      efficacy and nephrotoxicity of vancomycin in patients with methicillin-resistant
      Staphylococcus aureus pneumonia and evaluated the need to use peak concentration
      in therapeutic drug monitoring (TDM). METHODS: Serum drug concentrations of 31
      hospitalized patients treated with vancomycin for methicillin-resistant S. aureus
      pneumonia were collected. RESULTS: Significant differences in trough
      concentration (Cmin)/minimum inhibitory concentration (MIC) and area under the
      serum concentration-time curve (AUC0-24)/MIC were observed between the response
      and non-response groups. Significant differences in Cmin and AUC0-24 were
      observed between the nephrotoxicity and non-nephrotoxicity groups. Receiver
      operating characteristic curves revealed high predictive values of Cmin/MIC and
      AUC0-24/MIC for efficacy and of Cmin and AUC0-24 for safety of vancomycin.
      CONCLUSIONS: These results suggest little need to use peak concentration in
      vancomycin TDM because Cmin/MIC and Cmin are sufficient to predict the efficacy
      and safety of vancomycin.

PMID- 23147107
TI  - Neuronal IL-17 receptor upregulates TRPV4 but not TRPV1 receptors in DRG neurons
      and mediates mechanical but not thermal hyperalgesia.
AB  - In addition to the proinflammatory cytokines tumor necrosis factor-alpha,
      interleukin-6 and interleukin-1beta, the cytokine interleukin-17 (IL-17) is
      considered an important mediator of autoimmune diseases such as rheumatoid
      arthritis. Because tumor necrosis factor-alpha and interleukin-1beta have the
      potential to influence the expression of transduction molecules such as transient
      receptor potential vanilloid 1 (TRPV1) in dorsal root ganglion (DRG) neurons and
      thus to contribute to pain we explored in the present study whether IL-17A
      activates DRG neurons and influences the expression of TRPV1. The IL-17A receptor
      was visualized in most neurons in dorsal root ganglion (DRG) sections as well as
      in cultured DRG neurons. Upon long-term exposure to IL-17A, isolated and cultured
      rat DRG neurons showed a significant upregulation of extracellular-regulated
      kinase (ERK) and nuclear factor kappaB (NFkappaB). Long-term exposure of neurons
      to IL-17A did not upregulate the expression of TRPV1. However, we found a
      pronounced upregulation of transient receptor potential vanilloid 4 (TRPV4) which
      is considered a candidate transduction molecule for mechanical hyperalgesia. Upon
      the injection of zymosan into the paw, IL-17A-deficient mice showed less
      mechanical hyperalgesia than wild type mice but thermal hyperalgesia was not
      attenuated in IL-17A-deficient mice. These data show, therefore, a particular
      role of IL-17 in mechanical hyperalgesia, and they suggest that this effect is
      linked to an activation and upregulation of TRPV4.

PMID- 23147108
TI  - Cu-Zn superoxide dismutase activates muscarinic acetylcholine M1 receptor pathway
      in neuroblastoma cells.
AB  - Muscarinic receptors (mAChRs) control several neuronal functions and are widely
      expressed in the central nervous system (CNS): M1 subtype represents the
      predominant mAChR in the CNS. Previously, we showed that antioxidant enzyme Cu-Zn
      superoxide dismutase (SOD1) is secreted by many cellular lines and specifically
      interacts with cell surface membrane of human neuroblastoma SK-N-BE cells thus
      activating phospholipase C (PLC) transduction pathway and increasing
      intracellular calcium concentration ([Ca(2+)](i)). In addition, we demonstrated
      that a small amount of SOD1 is contained in large core dense vesicles and that it
      is secreted in response to depolarization induced by elevated extracellular K(+)
      concentration. In the present study, we investigated the involvement of
      muscarinic M1 receptors in SOD1-induced activation of PLC transduction pathway.
      We showed that, in SK-N-BE cells, SOD1 was able to activate muscarinic M1
      receptor producing a phosphorylation of ERK 1/2 and Akt in dose- and time
      dependent manner. Interestingly, in the presence of the M1 antagonist
      pirenzepine, ERK 1/2 and Akt phosphorylation induced by SOD1 was remarkably
      prevented. This effect was mimicked by knocking-down M1 receptor using two
      sequences of RNA silencing (siRNA). At functional level, siRNAs against M1
      receptor were able to prevent the increase in [Ca(2+)](i) induced by SOD1. The
      same inhibitory effect on [Ca(2+)](i) changes was produced by the M1 antagonist
      pirenzepine. Collectively, the results of this study demonstrated that SOD1 could
      activate a transductional pathway through the involvement of M1 muscarinic
      receptor.

PMID- 23147110
TI  - Adverse neuro-immune-endocrine interactions in patients with active tuberculosis.
AB  - The nervous, endocrine and immune systems play a crucial role in maintaining
      homeostasis and interact with each other for a successful defensive strategy
      against injurious agents. However, the situation is different in long-term
      diseases with marked inflammation, in which defensive mechanisms become altered.
      In the case of tuberculosis (TB), this is highlighted by several facts: an
      imbalance of plasma immune and endocrine mediators, that results in an adverse
      environment for mounting an adequate response against mycobacteria and
      controlling inflammation; the demonstration that dehidroepiandrosterone (DHEA)
      secretion by a human adrenal cell line can be inhibited by culture supernatants
      from Mycobacterium tuberculosis-stimulated peripheral blood mononuclear cells -
      PBMC - of TB patients, with this effect being partly reverted when neutralizing
      transforming growth factor-beta in such supernantants; the in vitro effects of
      adrenal steroids on the specific immune response of PBMC from TB patients, that
      is a cortisol inhibition of mycobacterial antigen-driven lymphoproliferation and
      interferon-gamma production as well as a suppression of TGF-beta production in
      DHEA-treated PBMC; and lastly the demonstration that immune and endocrine
      compounds participating in the regulation of energy sources and immune activity
      correlated with the consumption state of TB patients. Collectively, immune
      endocrine disturbances of TB patients are involved in critical components of
      disease pathology with implications in the impaired clinical status and
      unfavorable disease outcome. This article is part of a Special Issue entitled
      'Neuroinflammation in neurodegeneration and neurodysfunction'.

PMID- 23147111
TI  - MHC class I protein is expressed by neurons and neural progenitors in mid
      gestation mouse brain.
AB  - Proteins of the major histocompatibility complex class I (MHCI) are known for
      their role in the vertebrate adaptive immune response, and are required for
      normal postnatal brain development and plasticity. However, it remains unknown if
      MHCI proteins are present in the mammalian brain before birth. Here, we show that
      MHCI proteins are widely expressed in the developing mouse central nervous system
      at mid-gestation (E9.5-10.5). MHCI is strongly expressed in several regions of
      the prenatal brain, including the neuroepithelium and olfactory placode. MHCI is
      expressed by neural progenitors at these ages, as identified by co-expression in
      cells positive for neuron-specific class III beta-tubulin (Tuj1) or for Pax6, a
      marker of neural progenitors in the dorsal neuroepithelium. MHCI is also co
      expressed with nestin, a marker of neural stem/progenitor cells, in olfactory
      placode, but the co-localization is less extensive in other regions. MHCI is
      detected in the small population of post-mitotic neurons that are present at this
      early stage of brain development, as identified by co-expression in cells
      positive for neuronal microtubule-associated protein-2 (MAP2). Thus MHCI protein
      is expressed during the earliest stages of neuronal differentiation in the
      mammalian brain. MHCI expression in neurons and neural progenitors at mid
      gestation, prior to the maturation of the adaptive immune system, is consistent
      with MHCI performing non-immune functions in prenatal brain development. These
      results raise the possibility that disruption of the levels and/or patterns of
      MHCI expression in the prenatal brain could contribute to the pathogenesis of
      neurodevelopmental disorders.

PMID- 23147112
TI  - Special issue commentary: the changing face of inflammation in the brain.
AB  - The study of inflammation in the brain has been extended to include a wide range
      of conditions, but there remains plenty of argument over semantics and the
      precise definition of what constitutes inflammation in these pathologies. In this
      special issue, we sought to highlight the diversity of what is considered to be
      inflammation in the brain, and we have accepted that the presence of microglia
      cells with altered morphology remains a useful starting point. However, it is
      clear that whatever is the molecular expression profile that accompanies an
      activated microglial cell, it is not static and it is influenced by factors both
      intrinsic and extrinsic to the brain. This article is part of a Special Issue
      entitled 'Neuroinflammation in neurodegeneration and neurodysfunction'.

PMID- 23147109
TI  - Pleiotropic and isoform-specific functions for Pitx2 in superior colliculus and
      hypothalamic neuronal development.
AB  - Transcriptional regulation of gene expression during development is critical for
      proper neuronal differentiation and migration. Alternative splicing and
      differential isoform expression have been demonstrated for most mammalian genes,
      but their specific contributions to gene function are not well understood. In
      mice, the transcription factor gene Pitx2 is expressed as three different
      isoforms (PITX2A, PITX2B, and PITX2C) which have unique amino termini and common
      DNA binding homeodomains and carboxyl termini. The specific roles of these
      isoforms in neuronal development are not known. Here we report the onset of
      Pitx2ab and Pitx2c isoform-specific expression by E9.5 in the developing mouse
      brain. Using isoform-specific Pitx2 deletion mouse strains, we show that
      collicular neuron migration requires PITX2AB and that collicular GABAergic
      differentiation and targeting of hypothalamic projections require unique Pitx2
      isoform dosage. These results provide insights into Pitx2 dosage and isoform
      specific requirements underlying midbrain and hypothalamic development.

PMID- 23147114
TI  - Factors predicting severe childhood obesity in kindergarteners.
AB  - BACKGROUND: Severe obesity has increased >300% in US children since 1976, and is
      associated with multiple cardiovascular risk factors and high adult obesity
      rates. OBJECTIVE: The objective of this study was to identify predictors of
      severe obesity in kindergarteners. METHODS: Multivariable logistic regression and
      recursive partitioning analysis (RPA) were used to identify prenatal/pregnancy,
      infant, and early childhood predictors of severe kindergarten obesity (body mass
      index (BMI) 99th percentile) in the Early Childhood Longitudinal Study Birth
      Cohort, a nationally representative longitudinal study that followed children
      from birth through kindergarten. RESULTS: For the 6800 children, the severe
      kindergarten obesity prevalence was 5.7%, with higher adjusted odds for crossing
      the 85th percentile of BMI at 2 years old (odds ratio (OR), 8.0; 95% confidence
      interval (CI), 4.1-15.7), preschool age (OR, 7.9; 95% CI, 4.9-12.8) and 9 months
      old (OR, 1.8; 95% CI, 1.2-2.6); maternal severe obesity (OR, 3.4; 95% CI, 1.9
      5.8) and gestational diabetes (OR, 2.9; 95% CI, 1.5-5.5); drinking tea or coffee
      between meals/before bedtime at 2 years old (OR, 3.3; 95% CI, 1.3-8.5); Latino
      (OR, 2.3; 95% CI, 1.4-3.7) and multiracial (OR, 2.3; 95% CI, 1.1-4.8)
      race/ethnicity; and drinking sugary beverages at kindergarten age at least weekly
      (OR, 2.3; 95% CI, 1.4-3.7). Ever-attending center-based daycare (OR, 0.3; 95% CI,
      0.1-0.9), eating fruit at least weekly at kindergarten age (OR, 0.3; 95% CI, 0.1
      0.7), and maternal history of a prior newborn birth weight 4000 g (OR, 0.1; 95%
      CI, 0.02-0.6) were associated with reduced odds of severe obesity. RPA identified
      low severe obesity prevalence (1.9%) for non-85th BMI-percentile preschool
      crossers and high severe obesity (56-80%) for predictor clusters which included
      crossing the 85th BMI percentile at earlier ages, low parental education,
      specific maternal age cutoffs, preschooler bedtime rules, and outside
      walking/play frequency for 9-month-olds. CONCLUSIONS: Certain parental,
      prenatal/pregnancy, infant, and early childhood factors, both alone and in
      combination, are potent predictors of severe obesity in kindergarteners.

PMID- 23147113
TI  - EphB2 receptor forward signaling controls cortical growth cone collapse via Nck
      and Pak.
AB  - EphB receptors and their ephrinB ligands transduce bidirectional signals that
      mediate contact-dependent axon guidance primarily by promoting growth cone
      repulsion. However, how EphB receptor-mediated forward signaling induces axonal
      repulsion remains poorly understood. Here, we identify Nck and Pak proteins as
      essential forward signaling components of EphB2-dependent growth cone collapse in
      cortical neurons. We show that kinase-active EphB2 binds to Pak and promotes
      growth cone repulsion via Pak kinase activity, Pak-Nck binding, RhoA signaling
      and endocytosis. However, Pak's function in this context appears to be
      independent of Rac/Cdc42-GTP, consistent with the absence of Rac-GTP production
      after ephrinB treatment of cortical neurons. Taken together, our findings suggest
      that ephrinB-activated EphB2 receptors recruit a novel Nck/Pak signaling complex
      to mediate repulsive cortical growth cone guidance, which may be relevant for
      EphB forward signaling-dependent axon guidance in vivo.

PMID- 23147115
TI  - Increased insulin receptor substrate 2 expression is associated with
      steatohepatitis and altered lipid metabolism in obese subjects.
AB  - OBJECTIVE: The aim of this study was to evaluate whether dysregulation of
      molecules involved in FOXO1-dependent insulin signaling in the liver is
      associated with de novo lipogenesis (DNL) and altered lipid metabolism in
      severely obese subjects. DESIGN: Observational retrospective study. SUBJECTS: We
      considered 71 obese subjects (age 20-68 years; body mass index (BMI)>40 kg m(-2)
      or BMI>35 kg m(-2) in the presence of metabolic complications) classified into
      three groups according to liver histology: normal liver (n=12), simple steatosis
      (n=27) and nonalcoholic steatohepatitis (NASH; n=32). Key nodes in insulin
      signaling and gene expression of molecules implicated in insulin-dependent
      glucoregulatory pathway and DNL were evaluated by quantitative real-time PCR and
      western blotting. RESULTS: Patients with steatosis had decreased phosphorylation
      of the insulin kinase AKT1, mediating insulin receptor signaling, and the
      transcription factor FOXO1, which was therefore more active mediating insulin
      resistance at transcriptional level. Despite no changes in insulin receptor
      substrate (IRS)1 mRNA levels, the mRNA and protein levels of the FOXO1 target
      IRS2 increased progressively with the severity of steatosis from normal liver to
      NASH. IRS2 expression was correlated with the severity of steatosis, dyslipidemia
      and liver damage. In patients with NASH, upregulation of IRS2 was associated with
      preserved activation of AKT2, mediating the stimulating effect of insulin on DNL,
      and overexpression of its target sterol regulatory element-binding protein 1c
      (SREBP1c), inducing DNL at transcriptional level. Both FOXO1 and SREBP1c
      overexpression converged on upregulation of glucokinase, providing substrates for
      DNL, in NASH patients. CONCLUSION: Differential regulation of IRS1 and IRS2 and
      of their downstream effectors AKT1 and AKT2 is consistent with upregulation of
      FOXO1 and may justify the paradoxical state of insulin resistance relative to the
      glucoregulatory pathway and augmented insulin sensitivity of the liporegulatory
      pathway typical of steatosis and the metabolic syndrome in obese patients.

PMID- 23147116
TI  - Comorbidities in overweight children and adolescents: do we treat them
      effectively?
AB  - OBJECTIVE: The aim was to analyze the effectiveness of treatment concerning
      obesity-associated comorbidities in clinical practice. METHODS: A total of 11,681
      overweight children with >= 6-month follow-up treated at 175 centers specialized
      in pediatric obesity care in Central Europe were included in this analysis (mean
      body mass index (BMI) 29.0 +/- 5.6 kg m(-)(2), standard deviation score body mass
      index (SDS-BMI) 2.48 +/- 0.54, 45% boys, age 11.4 +/- 2.8 years). The changes of
      weight status, blood pressure, fasting lipids and glucose, and oral glucose
      tolerance tests were documented by standardized prospective quality documentation
      software (APV). RESULTS: After follow-up of in median 1.2 (interquartile range
      0.9-2.2) years, a mean reduction of -0.15 SDS-BMI was achieved. The prevalence of
      prehypertension (37->33%) and hypertension (17->12%) decreased, while prevalences
      of triglycerides >150 mg dl(-1) (22->21%), low-density-lipoprotein-cholesterol
      >130 mg dl(-1) (15->14%), impaired fasting glucose (6->6%) and impaired glucose
      tolerance (9->8%) remained stable. Drug treatment according to cutoffs
      recommended in European obesity guidelines were not frequently indicated
      (hypertension: 10%; dyslipidemia: 1%, type 2 diabetes <1%). None of the children
      with dyslipidemia received lipid-lowering drugs and only 1.4% of the children
      with hypertension were treated with antihypertensive drugs. CONCLUSIONS:
      Achieving sufficient weight loss to improve obesity associated comorbidities was
      difficult in clinical practice. Drug treatment of hypertension, dyslipidemia and
      type 2 diabetes was rarely performed even if it was indicated only in a minority
      of the overweight children. Future analyses should identify reasons for this
      insufficient drug treatment of comorbidities and analyze whether the benchmarking
      processes of APV improve medical care of childhood obesity.

PMID- 23147117
TI  - Association of nutrition in early life with body fat and serum leptin at adult
      age.
AB  - BACKGROUND: There is overwhelming evidence that experiences during early life
      could have long-term health consequences. However, the role of early nutrition in
      programming obesity and leptin resistance is still poorly understood. OBJECTIVE:
      We aimed at determining whether nutritional intakes in early life are associated
      with body composition and hormonal status at 20 years. SUBJECTS: Healthy infants
      participating in the two-decade-long prospective ELANCE (Etude Longitudinale
      Alimentation Nutrition Croissance des Enfants) study were examined at 10 months
      and 2 years. At 20 years, weight, height, subscapular and triceps skinfold
      thicknesses, fat mass (FM) and fat-free mass (FFM) assessed via bioelectrical
      impedance analysis, and serum leptin concentration were recorded in 73 subjects
      still participating in the follow-up. RESULTS: In adjusted linear regression
      models, an increase by 100 kcal in energy intake at 2 years was associated with
      higher subscapular skinfold thickness (beta=6.4% SF, 95% confidence interval 2.53
      10.30, P=0.002) and higher FFM (0.50 kg, 0.06-0.95, P=0.03) at 20 years. An
      increase by 1% energy from fat at 2 years was associated with lower subscapular
      skinfold thickness (-2.3% SF, -4.41 to -0.18, P=0.03), lower FM (-0.31 kg, -0.60
      to -0.01, P=0.04) and lower serum leptin concentration (-0.21 MUg l(-1), -0.39 to
      -0.03, P=0.02) at 20 years. CONCLUSIONS: Low-fat intake in early life was
      negatively associated with body fat (particularly at the trunk site) and serum
      leptin concentration at 20 years, suggesting that early low-fat intake could
      increase the susceptibility to develop overweight and leptin resistance at later
      ages. These findings substantiate current recommendations against restricting fat
      intake in early life and open new directions for investigating the origin of
      obesity.

PMID- 23147118
TI  - Eating behaviour in obese patients with melanocortin-4 receptor mutations: a
      literature review.
AB  - Melanocortin-4 receptor (MC4R) mutations are the most common known cause of
      monogenic obesity and an important contributor to polygenic obesity. MC4R
      mutations with partial or total loss of function, as well as the variant
      rs17782313 mapped near MC4R, are positively associated with obesity. MC4R is
      involved in the leptin-melanocortin signalling system, located in hypothalamic
      nuclei, that controls food intake via both anorexigenic or orexigenic signals.
      Impairment in this receptor might affect eating behaviours. Thus, in the case of
      MC4R mutation carriers, obesity could be related, at least partly, to inadequate
      control over eating behaviours. Many published studies address eating behaviours
      in MC4R mutation carriers. Most studies focus on binge eating disorder, whereas
      others examine various aspects of intake and motivation. Up to now, no evaluation
      of this literature has been performed. In this review, we examine the available
      literature on eating behaviours in carriers of MC4R mutations and variant
      rs17782313 near MC4R gene. We address binge eating disorder, bulimia nervosa,
      mealtime hyperphagia, snacking, psychological factors, satiety responsiveness and
      intake of energy and macro/micronutrient. In a small number of studies, MC4R
      mutations seem to impair eating behaviours or motivation, but no clear causal
      effects can be found in the balance of the evidence presented. Improvements in
      methodologies will be necessary to clarify the behavioural effects of MC4R
      mutations. 

PMID- 23147119
TI  - Expression of equilibrative nucleoside transporter 1 in rat circumvallate
      papillae.
AB  - In gustatory function, communication between four types taste buds cells plays
      crucial roles. ATP is one of the intercellular signaling molecules in taste buds,
      and the extracellular ATP fate is regulated by its cellular clearance, but there
      is little information on it. Therefore, we examined the expression profiles of
      nucleoside transporters (NTs) as a clearance system for ATP metabolite adenosine
      in rat circumvallate papillae (CP) by RT-PCR, real-time PCR and
      immunohistochemistry. Among NTs, mRNA for Ent1 was expressed by the CP, and
      significantly was greater in the CP as compared with non-CP. ENT1
      immunoreactivity was detected in PLC-beta2-positive type II (71.0+/-8.5%),
      chromogranin-A-positive type III (64.9+/-7.4%), and SNAP25-positive type III
      (77.0+/-10.4%) taste cells, but not in NTPDase2-positive type I ones. These
      results indicate that ENT1-expressing type II and III taste cells might comprise
      an adenosine clearance system in taste buds of the CP. ENT1 expression in taste
      cells is important for elucidation of complicated taste signaling.

PMID- 23147120
TI  - Mental rotation of a letter, hand and complex scene in microgravity.
AB  - Previous studies showed egocentric but not allocentric mental rotation tasks to
      be impaired in microgravity when feedback cues about vertical surroundings were
      restricted. Those studies are difficult to reconcile, however, since they were
      limited not only to small subject groups, but also differed dramatically in
      design. According to this lack, the present study was conducted in order to
      compare three typical egocentric and allocentric mental rotation stimuli in
      microgravity within a single experiment and using the same subjects and setup
      conditions. In order to simulate astronauts' working conditions in space, visual
      and tactile vertical references were provided. Six subjects mentally rotated
      letters, body parts, and complex scenes in parabolic flight during near
      weightlessness and level flight conditions. Subjects viewed letters and judged
      whether they were mirror-reversed or not (task LETTER), viewed pictures of a hand
      and assessed whether it was a right or a left hand (task HAND), and viewed
      drawings of a person at a table that contained both a weapon and a rose and had
      to decide whether the weapon was on the right or left side of the table (task
      SCENE). Material could be in canonical orientation or rotated from 0 degrees  up
      to 180 degrees  in +/-60 degrees  steps. We calculated reaction times and error
      scores for each task, orientation in each condition, and performed additionally
      intra-subject correlations between reaction times of both conditions for each
      task. We found typical reaction times and error scores for each stimulus category
      with increasing rotation level. More importantly, response time and error score
      were not impaired in microgravity, independent of stimulus type and orientation.
      This finding is further confirmed by correlation analysis. We conclude that the
      mental rotation of letters, hand shapes, and complex scenes is not affected by
      short periods in microgravity when visual and tactile vertical references are
      provided. This finding is relevant for astronauts who are normally aware of their
      surroundings, and it is in accordance with previous findings, where only
      egocentric stimuli were impaired in microgravity when sensory cues about the
      vertical reference were restricted.

PMID- 23147121
TI  - Do mirror neurons subserve action understanding?
AB  - Mirror neurons were once widely believed to support action understanding via
      motor simulation of the observed actions. Recent evidence regarding the
      functional properties of mirror neurons in monkeys as well as much
      neuropsychological evidence in humans has shown that this is not the case.

PMID- 23147123
TI  - Simulation of the performance of aerobic granular sludge SBR using modified ASM3
      model.
AB  - The activated sludge model No. 3 (ASM3) was modified to describe the biological
      reactions in aerobic granular sludge SBR. The simultaneous storage and growth,
      nitrification and denitrification were all accounted for in modified model. The
      sensitivities of effluent COD, NH(4)(+) -N, and TN toward the stoichiometric and
      kinetic coefficients were analyzed. A standard set of parameters obtained from a
      combination of literature data was chosen for the model. The experimental results
      for the time profile of COD, NH(4)(+) -N, and TN in a typical cycle were used to
      verify the ASM3 model. The verification results show the model established is
      applicable for simulating the perfo rmance of an aerobic granule-based SBR. A
      comparison of the measured and predicted values of substrate removal for both the
      modified ASM3 and the original ASM3 was also performed. The verification and
      comparison results show the modified ASM3 model describes the aerobic granule
      based SBR better and more mechanistically.

PMID- 23147122
TI  - No association of ZNF804A rs1344706 with white matter integrity in schizophrenia:
      a tract-based spatial statistics study.
AB  - Altered brain connectivity has been widely considered as a genetic risk mechanism
      for schizophrenia. Of the many susceptibility genes identified so far, ZNF804A
      (rs1344706) is the first common genetic variant associated with schizophrenia on
      a genome-wide level. Previous fMRI studies have found that carriers of rs1344706
      exhibit altered functional connectivity. However, the relationship between
      ZNF804A and white matter structural connectivity in patients of schizophrenia
      remains unknown. In this study, 100 patients with schizophrenia and 69 healthy
      controls were genotyped at the single nucleotide polymorphism rs1344706.
      Diffusion tensor imaging (DTI) was conducted and analyzed with tract-based
      spatial statistics. Systematic statistical analysis was conducted on multiple
      diffusion indices, including fractional anisotropy, axial diffusivity, radial
      diffusivity, and mean diffusivity. Unpaired two-sample t-test revealed
      significant differences in fractional anisotropy and diffusivity between
      schizophrenia and control groups. A two-way ANOVA analysis was conducted to
      assess the main effects of and the interaction between schizophrenia and ZNF804A.
      Although significant main effects of the diagnosis of schizophrenia were found on
      radial diffusivity, no association between the ZNF804A (rs1344706) and white
      matter connectivity was found in the entire group of subjects or in a selected
      subgroup of age-matched subjects (n=72).

PMID- 23147124
TI  - Ettlia sp. YC001 showing high growth rate and lipid content under high CO2.
AB  - Over 100 green-colored colonies were isolated from environmental samples when
      cultivating on a BG11 agar medium, and 4 strains showing different morphologies
      were selected based on light microscopic observation. Among these strains, the
      microalgal species with the highest growth rate under 10% CO(2) was identified as
      Ettlia sp. YC001 using an 18S rDNA-based phylogenetic analysis and morphological
      comparison. The highest cell density of 3.10 g/L (based on dry cell weight) and
      biomass productivity of 0.19 g/L/d were obtained under 5% CO(2) after 16 days.
      The lipid content and productivity were also up to 42% of the dry cell weight and
      80.0mg/L/d, respectively. The color of the Ettlia sp. YC001 culture changed from
      green to red after a month due to the accumulation of certain carotenoids.
      Therefore, it would seem that Ettlia sp. YC001 is appropriate for mitigating
      CO(2) due to its high biomass productivity, and a suitable candidate for
      producing biodiesel and high-value products.

PMID- 23147125
TI  - Facet-induced formation of hematite mesocrystals with improved lithium storage
      properties.
AB  - In this study, we prepared high-stability hematite mesocrystals by a facile route
      without polymer additives. In particular, the rhombic hematite mesocrystals
      exhibit excellent lithium insertion behavior compared to the hematite single
      crystals.

PMID- 23147126
TI  - Staging of mental disorders: systematic review.
AB  - BACKGROUND: The staging method, whereby a disorder is characterized according to
      its seriousness, extension, development and features, is attracting increasing
      attention in clinical psychology and psychiatry. The aim of this systematic
      review was to critically summarize the tools that are available for reproducing
      and standardizing the clinical intuitions that are involved in a staging
      formulation. METHODS: A comprehensive research was conducted on the MEDLINE,
      PsycINFO, EMBASE and Cochrane databases from inception to May 2012. The following
      search terms were used: 'stage/staging' AND 'psychiatric disorder/mental
      disorder/schizophrenia/mood disorder/anxiety disorder/substance use
      disorder/eating disorder'. RESULTS: A total of 78 studies were identified for
      inclusion in the review. We discussed studies addressing or related to the issue
      of staging in a number of mental disorders (schizophrenia, unipolar depression,
      bipolar disorder, panic disorder, substance use disorders, anorexia and bulimia
      nervosa). The literature indicates that disorders have a longitudinal development
      or a treatment history that can be categorized according to stages. We proposed
      staging formulations for the above-mentioned psychiatric disorders. CONCLUSION:
      Staging models offer innovative assessment tools for clinical psychologists and
      psychiatrists. Characterizing each stage of an illness demarcates major
      prognostic and therapeutic differences among patients who otherwise seem to be
      deceptively similar since they share the same psychiatric diagnosis. A stage 0 to
      denote an at-risk condition does not appear to be warranted at the current state
      of research.

PMID- 23147127
TI  - Reliability and validity of three functional tests in ambulatory patients with
      spinal cord injury.
AB  - STUDY DESIGN: A cross-sectional study. OBJECTIVES: To investigate reliability,
      discriminative ability and concurrent validity of three functional tests
      (including the 10-meter walk test (10MWT), timed up and go test (TUGT) and five
      times sit-to-stand test (FTSST)) using the Functional Independence Measure
      Locomotor (FIM-L) scores as a standard criterion. SETTING: A tertiary
      rehabilitation center, Thailand. METHODS: Subjects were 66 patients with spinal
      cord injury (SCI), who were able to walk at least 50 m unassisted with or without
      a walking device (FIM-L scores 6-7). They were tested for functional ability
      using the 10MWT, TUGT and FTSST. Sixteen subjects also assessed the ability using
      three assessors to evaluate the inter-tester reliability of the tools. RESULTS:
      The three functional tests demonstrated excellent inter-tester reliability
      (intraclass correlation coefficient (3,3)=0.997-1.00) and could clearly
      distinguish between subjects who walked with and without a walking device. In
      addition, the tests showed significant correlation with walking categories or FIM
      L scores (r(pb)=0.778, -0.692 and -0.595 for the 10MWT, TUGT and FTSST,
      respectively, P<0.001). CONCLUSION: The findings support reliability and validity
      of the 10MWT, TUGT and FTSST to assess levels of independences in ambulatory
      subjects with SCI.

PMID- 23147129
TI  - Quality of life after spinal cord injury: a comparison across six countries.
AB  - STUDY DESIGN: An international cross-sectional study. OBJECTIVE: To examine the
      quality of life (QoL) of people with spinal cord injury (SCI) across six
      countries worldwide, controlling for socio-demographic and lesion-related sample
      characteristics and using a cross-culturally valid assessment. METHODS: Data from
      243 persons with SCI from Australia, Brazil, Canada, Israel, South Africa and the
      United States were analyzed. QoL was measured using five satisfaction items from
      the World Health Organization Quality of Life Assessment. Cross-culturally valid,
      Rasch-transformed scores were used for comparison. RESULTS: Analysis of variance
      showed a significant difference in QoL between countries (F=3.938; df=5;
      P=0.002). Shorter time since injury, no paid employment and living in Brazil were
      significant predictors of lower QoL, explaining 13% of variance in linear
      regression. Using multilevel regression with country as higher-order variable,
      time since injury and paid employment remained significant predictors and
      explained 18% of variance in QoL. The intraclass correlation coefficient (0.05)
      indicates that 5% of the variability can be accounted for by country. CONCLUSION:
      This study showed QoL differences between countries that could not be explained
      by differences in demographic and lesion-related characteristics. Results point
      to the relevance of reintegration of people with SCI into the workforce. Further
      international comparative research using larger samples is recommended.

PMID- 23147131
TI  - Is the emergency department an appropriate substitute for primary care for
      persons with traumatic spinal cord injury?
AB  - STUDY DESIGN: Retrospective cohort with linkage of administrative data sets.
      OBJECTIVES: To describe the patterns (for example, number of visits by year post
      injury) and characteristics of the emergency department (ED) visits (for example,
      acuity level, timing of visits, reasons for visits) made by persons with
      traumatic spinal cord injury (TSCI) over a 6-year period following injury.
      SETTINGS: Ontario, Canada. METHODS: Rates of ED utilization and reasons for ED
      visits were calculated between the fiscal years 2003-2009. Reasons for visits
      were categorized by acuity level: potentially preventable visits were defined as
      visits related to ambulatory sensitive conditions; low acuity and high acuity
      visits were defined by the Canadian Triage and Acuity Scale. RESULTS: The total
      number of ED visits for the 6-year period is 4403 (n=1217). Of these visits, 752
      (17%) were classified as potentially preventable, 1443 (33%) as low acuity and
      2208 (50%) as high acuity. The majority of patients, regardless of acuity level,
      did not see a primary care practitioner on the day of the ED visit and most
      visits occurred during the weekday (Mon-Fri 0700-1659 hours). ED use was highest
      in the first year but remained high over the subsequent years. For potentially
      preventable visits, the majority of visits were related to urinary tract
      infections (n=385 visits, 51.2%), followed by pneumonia (n=91, 12.1%).
      CONCLUSION: Given the high rates of ED use for low acuity and potentially
      preventable conditions, these results suggest that the ED is being used as an
      inappropriate substitute for primary care for individuals with TSCI 50% of the
      time.

PMID- 23147130
TI  - Hypertension and antihypertensive treatment in veterans with spinal cord injury
      and disorders.
AB  - OBJECTIVES: Hypertension (HTN) is an important risk factor for cardiovascular
      disease, a major cause of morbidity and mortality among people with spinal cord
      injury and disorders (SCI/D). Our study examined prevalence, associated factors,
      and pharmacological treatment of HTN in Veterans with SCI/D compared with a
      matched control group. METHODS: A retrospective review was conducted of Veterans
      with traumatic SCI/D (TSCI/D; n=6672), non-traumatic SCI/D (NTSCI/D; n=3566) and
      a matched, non-injured cohort. RESULTS: Over half of patients with TSCI/D (56.6%)
      had HTN, compared with 68.4% of matched controls (P<0.001). Paraplegic and
      tetraplegic Veterans with TSCI/D had significantly lower odds of having a HTN
      diagnosis compared with control (odds ratios (OR)=0.84 (0.77-0.91); OR=0.38 (0.35
      0.42)). About 71.8% of patients with NTSCI/D had HTN compared with 72.3% of
      matched controls (P>0.05). Paraplegic and tetraplegic Veterans with NTSCI/D did
      not have significantly different odds of a HTN diagnosis compared with control
      (OR=0.92 (0.79-1.05); OR=0.85 (0.71-1.01)). Adjusted analysis indicates that
      Veterans with tetraplegia and HTN were less likely to receive antihypertensive
      therapy (TSCI/D, OR=0.62 (0.53-0.71); NTSCI/D, OR=0.81 (0.66-0.99)). CONCLUSION:
      HTN appears to be more prevalent in SCI/D Veterans than previously reported.
      TSCI/D Veterans have a significantly lower prevalence of HTN whereas NTSCI/D
      Veterans have a comparable prevalence of HTN to those without SCI/D. The level of
      injury (tetraplegia vs paraplegia) has a large impact on the prevalence of HTN in
      the traumatic cohort. Subsequent antihypertensive therapy is used less in both
      TSCI/D and NTSCI/D Veterans with tetraplegia and more in TSCI/D Veterans with
      paraplegia.

PMID- 23147132
TI  - Editorial note on: agreement of repeated motor and sensory scores at individual
      myotomes and dermatomes in young persons with spinal cord injury.

PMID- 23147133
TI  - Agreement of repeated motor and sensory scores at individual myotomes and
      dermatomes in young persons with spinal cord injury.
AB  - STUDY DESIGN: A prospective repeated measures multicenter study to determine
      reliability at individual spinal levels when applied to young persons with spinal
      cord injury (SCI). OBJECTIVES: To evaluate intra- and inter-rater agreement of
      repeated motor and sensory scores at individual spinal levels. SETTING: Shriners
      Hospitals for Children--Philadelphia and Chicago, USA. METHODS: A total 189 youth
      with complete and incomplete SCI underwent four neurological exams by two
      different raters. Agreement between and within raters for each myotome and
      dermatome was evaluated for complete and incomplete SCI separately. Intraclass
      correlation coefficients and 95% confidence intervals were calculated. RESULTS:
      Overall, both intra- and inter-rater agreement resulted in moderate-to-high
      agreement among myotomes. Subjects with complete SCI had moderate agreement for
      light touch (LT) and pin prick (PP) testing, whereas subjects with incomplete SCI
      had >60.0% of dermatomes resulting in poor agreement for PP testing. CONCLUSION:
      Overall, moderate-to-high agreement was found for muscle strength comparisons and
      moderate-to-poor agreement was found for PP and LT.

PMID- 23147134
TI  - Effects of different bladder management methods on the quality of life in
      patients with traumatic spinal cord injury.
AB  - STUDY DESIGN: Multi-center, cross-sectional study. OBJECTIVES: To investigate the
      effects of different bladder management methods on the quality of life (QoL) in
      patients with spinal cord injury (SCI). SETTING: Turkey. METHODS: Consecutive SCI
      patients (n=195, 74.4% males), for whom at least 6 months had elapsed since the
      injury, were included and evaluated in five groups: normal spontaneous
      micturition (NSM), micturition with assisted maneuvers (MAM), aseptic
      intermittent catheterization by patient (IC-P), aseptic IC by an
      attendant/caregiver (IC-A) and indwelling catheterization. The King's Health
      Questionnaire was used to evaluate the patients' QoL. RESULTS: The bladder
      management groups were similar regarding age, time elapsed since injury,
      education level, marital and occupational status. There was no difference among
      the groups in general health perception, personal relationships and sleep/energy
      domain scores. While the NSM group had generally the lowest scores, that is,
      better QoL, the IC-A group had the highest scores, that is, poorer QoL, in most
      of the domains. When the patients were grouped according to the frequency of
      urinary incontinence or American Spinal Injury Association Impairment Scale
      grades, no difference was found in the domain scores of the groups except the
      symptom severity domain scores. No significant difference was found between
      paraplegic and tetraplegic patients in the King's Health Questionnaire domains.
      CONCLUSION: The QoL was notably affected in SCI patients in IC-A group and
      negative effects on emotional status, physical and social activity limitations
      were observed, as well.

PMID- 23147135
TI  - Engagement in occupational activities and pressure ulcer development in
      rehabilitated South Indian persons with spinal cord injury.
AB  - STUDY DESIGN: Cross-sectional survey. OBJECTIVE: To compare the relationship
      between engagement in occupational activities and pressure ulcer (PU) development
      in persons with spinal cord injury (SCI). STUDY SETTING: Tertiary care university
      teaching hospital, Tamil Nadu, India. METHOD: One hundred and eight persons with
      SCI who were previously rehabilitated from our center were included in the study.
      A questionnaire was developed to collect information about occupational
      activities and particulars of PU development. RESULTS: The comparison between
      work, self-care and leisure with PU development showed no significant
      correlation. However, completeness of the SCI was found to be associated with PU
      development. The study also found a relationship between the type of work
      patients did and the severity of the PU they developed. CONCLUSION: This study
      clearly indicates that poor pressure relief practices lead to PU development in
      persons with SCI, irrespective of their level of independence, employment status
      or leisure pursuits thus hampering their functional independence at home, work
      and in daily activities that subsequently reduces their quality of life.

PMID- 23147136
TI  - Clinical efficacy of intravesical electrostimulation on incomplete spinal cord
      patients suffering from chronic neurogenic non-obstructive retention: a 15-year
      single centre retrospective study.
AB  - OBJECTIVE: To evaluate the clinical and urodynamic impact of intravesical
      electrostimulation (IVES) on incomplete spinal cord injury (SCI) patients
      suffering from chronic neurogenic non-obstructive urinary retention (N-NOR).
      METHODS: One-hundred and two patients underwent at least 28 consecutive daily
      IVES sessions because objective evidence of detrusor acontractility instead of
      hypocontractility was detected. Diary entries written at various stages by each
      patient were compared (7 days before the IVES cycle, 15-21 days into the cycle
      and 7 days before its end). Responders were patients with a mean 50% reduction in
      both the number of daily catheterizations and post-void residual urine.
      Responders underwent further urodynamics at the end of the IVES cycle; patients
      experiencing first sensation of bladder filling, and the mean volume of first
      sensation of bladder filling per ml, Qmax ml s(-1), among others, were evaluated.
      Nineteen individuals who repeated another IVES round were included in this study.
      RESULTS: Thirty-eight subjects (37.2%) responded to IVES and of those, 83.3%
      recovered the first sensation of bladder filling after the IVES round. Nineteen
      responders repeated IVES within 1 year, owing to loss of efficacy. They obtained
      similar voiding symptoms improvement and urodynamic results as after the first
      IVES cycle. A timespan of <2 years from SCI to IVES, and the presence of first
      sensation of bladder filling at baseline represented significant predictive
      parameters for IVES success (P<0.05) using chi(2)-test. CONCLUSIONS: IVES
      represents a possible therapeutic option for incomplete SCI patients with N-NOR.

PMID- 23147137
TI  - New approaches in antimalarial drug discovery and development: a review.
AB  - Malaria remains a major world health problem following the emergence and spread
      of Plasmodium falciparum that is resistant to the majority of antimalarial drugs.
      This problem has since been aggravated by a decreased sensitivity of Plasmodium
      vivax to chloroquine. This review discusses strategies for evaluating the
      antimalarial activity of new compounds in vitro and in animal models ranging from
      conventional tests to the latest high-throughput screening technologies.
      Antimalarial discovery approaches include the following: the discovery of
      antimalarials from natural sources, chemical modifications of existing
      antimalarials, the development of hybrid compounds, testing of commercially
      available drugs that have been approved for human use for other diseases and
      molecular modelling using virtual screening technology and docking. Using these
      approaches, thousands of new drugs with known molecular specificity and active
      against P. falciparum have been selected. The inhibition of haemozoin formation
      in vitro, an indirect test that does not require P. falciparum cultures, has been
      described and this test is believed to improve antimalarial drug discovery.
      Clinical trials conducted with new funds from international agencies and the
      participation of several industries committed to the eradication of malaria
      should accelerate the discovery of drugs that are as effective as artemisinin
      derivatives, thus providing new hope for the control of malaria.

PMID- 23147138
TI  - Oral live attenuated human rotavirus vaccine (RotarixTM) offers sustained high
      protection against severe G9P[8] rotavirus gastroenteritis during the first two
      years of life in Brazilian children.
AB  - In a large Phase III trial conducted in 10 Latin American countries, the safety
      and efficacy of the live attenuated monovalent rotavirus vaccine RIX4414 was
      evaluated in 15,183 healthy infants followed up during the first two years of
      life. Belem was the only site in Brazil included in this multicentre trial. The
      study in Belem included a subset of 653 infants who were followed up until 24
      months of age for protection against severe rotavirus gastroenteritis. These
      subjects were randomly assigned in a 1:1 ratio to receive two doses of vaccine (n
      = 328) or two doses of placebo (n = 325) at approximately two and four months of
      age. Of the 653 enrolled infants, 23 dropped out during the study period. For the
      combined two-year period, the efficacy of RIX4414 was 72.3% [95% confidence
      interval (CI) 37.5-89.1%] against severe rotavirus-related gastroenteritis,
      reaching a protection rate of 81.8% (95% CI 36.4-96.6%) against circulating wild
      type G9 rotavirus strains. It is concluded that two doses of RIX4414 are highly
      efficacious against severe rotavirus gastroenteritis in Belem during the first
      two years of life and provide high protection against the worldwide emergence and
      spread of G9P[8] strains.

PMID- 23147139
TI  - Phaeohyphomycosis: a clinical-epidemiological and diagnostic study of eighteen
      cases in Rio Grande do Sul, Brazil.
AB  - The goal of this study was to review 18 cases of phaeohyphomycosis in Rio Grande
      do Sul. The records of all of the patients with a diagnosis of phaeohyphomycosis
      between 1995-2010 were reviewed. Twelve of the 18 patients (66.6%) were male. The
      average age of the patients was 50 years old (range: 16-74 years). Eleven
      patients (61%) presented with subcutaneous lesions. Seven patients (38.8%) had
      received a solid organ transplant. In all of the cases, the presence of melanin
      in the fungal cells was determined by Fontana-Masson staining of tissue sections
      and documented. Among the 18 patients, a total of 11 different fungal species
      were isolated. The causative organisms included Exophiala jeanselmei, Alternaria,
      Curvularia, Cladophialophora and Colletotrichum gloeosporioides. To our
      knowledge, this review reports the first case of subcutaneous phaeohyphomycosis
      caused by C. gloeosporioides in a lung transplant patient. The number of reported
      cases of phaeohyphomycosis has increased in the last decade. In a number of
      cases, this increased incidence may be primarily attributed to iatrogenic
      immunodeficiency.

PMID- 23147140
TI  - In vitro susceptibility of Plasmodium falciparum Welch field isolates to
      infusions prepared from Artemisia annua L. cultivated in the Brazilian Amazon.
AB  - Artemisinin is the active antimalarial compound obtained from the leaves of
      Artemisia annua L. Artemisinin, and its semi-synthetic derivatives, are the main
      drugs used to treat multi-drug-resistant Plasmodium falciparum (one of the human
      malaria parasite species). The in vitro susceptibility of P. falciparum K1 and
      3d7 strains and field isolates from the state of Amazonas, Brazil, to A. annua
      infusions (5 g dry leaves in 1 L of boiling water) and the drug standards
      chloroquine, quinine and artemisinin were evaluated. The A. annua used was
      cultivated in three Amazon ecosystems (varzea, terra preta de indio and terra
      firme) and in the city of Paulinia, state of Sao Paulo, Brazil. Artemisinin
      levels in the A. annua leaves used were 0.90-1.13% (m/m). The concentration of
      artemisinin in the infusions was 40-46 mg/L. Field P. falciparum isolates were
      resistant to chloroquine and sensitive to quinine and artemisinin. The average
      50% inhibition concentration values for A. annua infusions against field isolates
      were 0.11-0.14 MUL/mL (these infusions exhibited artemisinin concentrations of
      4.7-5.6 ng/mL) and were active in vitro against P. falciparum due to their
      artemisinin concentration. No synergistic effect was observed for artemisinin in
      the infusions.

PMID- 23147141
TI  - Biogeographical aspects of the occurrence of Nyssomyia neivai and Nyssomyia
      intermedia (Diptera: Psychodidae) in a sympatric area of the Brazilian savannah.
AB  - Nyssomyia intermedia and Nyssomyia neivai constitute a species complex associated
      with Leishmania transmission. The aim of this study was to analyse the ecological
      profiles of the Ny. intermedia and Ny. neivai populations in a sympatric area in
      the Brazilian savannah along the banks of the Velhas River. Captures were
      performed from July 2003-June 2005 in two distinct environments: a gallery forest
      with various degrees of anthropogenic modification and animal shelters. A total
      of 20,508 Ny. neivai (86%) and Ny. intermedia (14%) sandflies were collected. The
      difference between the proportions of the sandflies that were collected (Ny.
      neivai/Ny. intermedia) per bank was significant. The right bank presented a
      greater number of sandflies (65%) and more preserved vegetation. The abundance of
      Ny. neivai was higher than that of Ny. intermedia on both banks. The results
      demonstrate that anthropic activities can affect the sandfly populations in this
      area, thereby leading to a reduction in species abundance. Nevertheless, the
      environments with higher levels of antropogenic modification displayed sandfly
      population numbers that favour the Leishmania transmission cycle.

PMID- 23147142
TI  - The combination of three faecal parasitological methods to improve the diagnosis
      of schistosomiasis mansoni in a low endemic setting in the state of Ceara,
      Brazil.
AB  - Laboratory diagnosis of intestinal schistosomiasis mansoni can be accomplished
      through various methods of stool examination to detect parasites, ranging from
      the most classic tests (Kato-Katz) to several methods that are still undergoing
      validation. This study was conducted to assess two new parasite identification
      methods for diagnosing schistosomiasis mansoni in residents of a low endemic area
      in the municipality of Maranguape, in the state of Ceara, Brazil using the Kato
      Katz method as a reference and serology (enzyme-linked immunosorbent assay) for
      the screening of patients. The Kato-Katz, the saline gradient method and the
      Helmintex((r)) method parasite identification methods were employed only in
      subjects who exhibited positive serologic tests. The test results were then
      analysed and treatment of positive individuals was subsequently performed. After
      comparing the test results, we observed that the saline gradient method and the
      Helmintex((r)) method were more effective in diagnosing schistosomiasis mansoni
      in the study area compared with the Kato-Katz method.

PMID- 23147143
TI  - Vector control intervention towards interruption of transmission of Chagas
      disease by Rhodnius prolixus, main vector in Guatemala.
AB  - In Guatemala, the Ministry of Health (MoH) began a vector control project with
      Japanese cooperation in 2000 to reduce the risk of Chagas disease infection.
      Rhodnius prolixus is one of the principal vectors and is targeted for
      elimination. The control method consisted of extensive residual insecticide
      spraying campaigns, followed by community-based surveillance with selective
      respraying. Interventions in nine endemic departments identified 317 villages
      with R. prolixus of 4,417 villages surveyed. Two cycles of residual insecticide
      spraying covered over 98% of the houses in the identified villages. Fourteen
      villages reinfestated were all resprayed. Between 2000-2003 and 2008, the number
      of infested villages decreased from 317 to two and the house infestation rate
      reduced from 0.86% to 0.0036%. Seroprevalence rates in 2004-2005, when compared
      with an earlier study in 1998, showed a significant decline from 5.3% to 1.3%
      among schoolchildren in endemic areas. The total operational cost was US$
      921,815, where the cost ratio between preparatory, attack and surveillance phases
      was approximately 2:12:1. In 2008, Guatemala was certified for interruption of
      Chagas disease transmission by R. prolixus. What facilitated the process was
      existing knowledge in vector control and notable commitment by the MoH, as well
      as political, managerial and technical support by external stakeholders.

PMID- 23147144
TI  - A single nucleotide polymorphism, rs129679860, in the IL28B locus is associated
      with the viral kinetics and a sustained virological response in a chronic,
      monoinfected hepatitis C virus genotype-1 Brazilian population treated with
      pegylated interferon-ribavirin.
AB  - Single nucleotide polymorphisms (SNPs) in the interleukin (IL)28B locus have been
      associated with a sustained virological response (SVR) in interferon-ribavirin
      (IFN-RBV)-treated chronic hepatitis C virus (HCV)-infected patients in European
      and African populations. In this study, the genotype frequency of two IL28B SNPs
      (rs129679860 and rs8099917) in a cohort of chronic HCV-monoinfected patients in
      Brazil was evaluated and the SNP sufficient to predict the treatment response
      outcome was determined. A total of 66 naive genotype-1 chronic HCV-infected
      patients were genotyped and the associated viral kinetics and SVR were assessed.
      The overall SVR was 38%. Both the viral kinetics and SVR were associated with
      rs129679860 genotypes (CC = 62% vs. CT = 33% vs. TT = 18%, p = 0.016). However,
      rs8099917 genotypes were only associated with SVR (TT = 53% vs. TG = 33% vs. GG =
      18%; p = 0.032). In this population, the analysis of a single SNP, rs12979860,
      successfully predicts SVR in the IFN-RBV treatment of HCV.

PMID- 23147145
TI  - The performance of laboratory tests in the management of a large outbreak of
      orally transmitted Chagas disease.
AB  - Orally transmitted Chagas disease (ChD), which is a well-known entity in the
      Brazilian Amazon Region, was first documented in Venezuela in December 2007, when
      103 people attending an urban public school in Caracas became infected by
      ingesting juice that was contaminated with Trypanosoma cruzi. The infection
      occurred 45-50 days prior to the initiation of the sampling performed in the
      current study. Parasitological methods were used to diagnose the first nine
      symptomatic patients; T. cruzi was found in all of them. However, because this
      outbreak was managed as a sudden emergency during Christmas time, we needed to
      rapidly evaluate 1,000 people at risk, so we decided to use conventional serology
      to detect specific IgM and IgG antibodies via ELISA as well as indirect
      haemagglutination, which produced positive test results for 9.1%, 11.9% and 9.9%
      of the individuals tested, respectively. In other more restricted patient groups,
      polymerase chain reaction (PCR) provided more sensitive results (80.4%) than
      blood cultures (16.2%) and animal inoculations (11.6%). Although the classical
      diagnosis of acute ChD is mainly based on parasitological findings, highly
      sensitive and specific serological techniques can provide rapid results during
      large and severe outbreaks, as described herein. The use of these serological
      techniques allows prompt treatment of all individuals suspected of being
      infected, resulting in reduced rates of morbidity and mortality.

PMID- 23147146
TI  - Polymerase chain reaction for the evaluation of Schistosoma mansoni infection in
      two low endemicity areas of Minas Gerais, Brazil.
AB  - This study aimed to evaluate the occurrence of schistosomiasis in areas with low
      endemicity using polymerase chain reaction (PCR) as a diagnostic method. We
      analysed faecal samples from 219 individuals residing in Piau and Coronel
      Pacheco, state of Minas Gerais, Brazil, using a single faecal sample from each
      individual and two slides of the Kato-Katz technique as a gold standard. Fifteen
      out of the 219 samples were positive with both methods of diagnosis. One sample
      was diagnosed as positive by the Kato-Katz technique only and 61 were diagnosed
      only by PCR. The positivity rates were 7.3% with the Kato-Katz method and 34.7%
      with PCR. When both techniques were assumed to have 100% specificity and positive
      individuals were identified by both methods, the sensitivity of the Kato-Katz
      method was 20.8% and the PCR sensitivity was 98.7%. The Kappa index between the
      two techniques was 0.234, suggesting weak agreement. The assessment of a single
      faecal sample by PCR detected more cases of infection than the analysis of one
      sample with two slides using the Kato-Katz technique, suggesting that PCR can be
      a useful diagnostic tool, particularly in areas with low endemicity.

PMID- 23147147
TI  - Fast test for assessing the susceptibility of Mycobacterium tuberculosis to
      isoniazid and rifampin by real-time PCR.
AB  - Mycobacterium tuberculosis is the bacterium that causes tuberculosis (TB), a
      leading cause of death from infectious disease worldwide. Rapid diagnosis of
      resistant strains is important for the control of TB. Real-time polymerase chain
      reaction (RT-PCR) assays may detect all of the mutations that occur in the M.
      tuberculosis 81-bp core region of the rpoB gene, which is responsible for
      resistance to rifampin (RIF) and codon 315 of the katG gene and the inhA
      ribosomal binding site, which are responsible for isoniazid (INH). The goal of
      this study was to assess the performance of RT-PCR compared to traditional
      culture-based methods for determining the drug susceptibility of M. tuberculosis.
      BACTEC TM MGIT TM 960 was used as the gold standard method for phenotypic drug
      susceptibility testing. Susceptibilities to INH and RIF were also determined by
      genotyping of katG, inhA and rpoB genes. RT-PCR based on molecular beacons probes
      was used to detect specific point mutations associated with resistance. The
      sensitivities of RT-PCR in detecting INH resistance using katG and inhA targets
      individually were 55% and 25%, respectively and 73% when combined. The
      sensitivity of the RT-PCR assay in detecting RIF resistance was 99%. The median
      time to complete the RT-PCR assay was three-four hours. The specificities for
      tests were both 100%. Our results confirm that RT-PCR can detect INH and RIF
      resistance in less than four hours with high sensitivity.

PMID- 23147148
TI  - Tuberculosis in a southern Brazilian prison.
AB  - The occurrence of tuberculosis (TB) in prisons has been described as an alarming
      public health problem in many countries, especially in developing nations. The
      objective of this study was to conduct a survey among prisoners with TB
      respiratory symptoms in order to estimate the incidence of the disease, to
      analyze the drug susceptibility profile and genotype the isolates of
      Mycobacterium tuberculosis in the city of Charqueadas, southern of Brazil. The TB
      incidence was 55/1,900 inhabitants in the prison; this corresponds to an
      incidence of 3,789/100,000 inhabitants, with a prevalence of 72/1,900
      (4,960/100,000 inhabitants). Drug susceptibility test was performed and, among
      the analyzed isolates, 85% were susceptible to all drugs tested and 15% were
      resistant to at least one drug, of which 89% were resistant only to isoniazid
      (INH) or in combination with another drug. The genotype classification of
      spoligotyping analysis showed that 40% of the isolates belong to LAM family, 22%
      to T family, 17.5% to Haarlem family, 12.5% to U family and 3% to X family. The
      shared international spoligotypes most frequently found were 729 (27%), 50
      (9.5%), 42 (8%), 53 (8%) and 863 (8%). In conclusion, it was observed that TB in
      this specific population had been caused, mostly, by strains that have been
      transmitted in the last few years, as demonstrated by the large level of genotype
      clustering. In addition, it was found specific large clusters, which were not
      often found in the general population from the same period and in the same
      region.

PMID- 23147149
TI  - Fitness evaluation of two Brazilian Aedes aegypti field populations with distinct
      levels of resistance to the organophosphate temephos.
AB  - In Brazil, decades of dengue vector control using organophosphates and
      pyrethroids have led to dissemination of resistance. Although these insecticides
      have been employed for decades against Aedes aegypti in the country, knowledge of
      the impact of temephos resistance on vector viability is limited. We evaluated
      several fitness parameters in two Brazilian Ae. aegypti populations, both
      classified as deltamethrin resistant but with distinct resistant ratios (RR) for
      temephos. The insecticide-susceptible Rockefeller strain was used as an
      experimental control. The population presenting the higher temephos resistance
      level, Aparecida de Goiania, state of Goias (RR(95) of 19.2), exhibited
      deficiency in the following four parameters: blood meal acceptance, amount of
      ingested blood, number of eggs and frequency of inseminated females. Mosquitoes
      from Boa Vista, state of Roraima, the population with lower temephos resistance
      level (RR(95) of 7.4), presented impairment in only two parameters, blood meal
      acceptance and frequency of inseminated females. These results indicate that the
      overall fitness handicap was proportional to temephos resistance levels. However,
      it is unlikely that these disabilities can be attributed solely to temephos
      resistance, since both populations are also resistant to deltamethrin and harbour
      the kdr allele, which indicates resistance to pyrethroids. The effects of reduced
      fitness in resistant populations are discussed.

PMID- 23147150
TI  - Comparison of adverse events following immunization with pandemic influenza A
      (H1N1)pdm09 vaccine with or without adjuvant among health professionals in Rio de
      Janeiro, Brazil.
AB  - A vaccination campaign against pandemic influenza A (H1N1)pdm09 was held in
      Brazil in March 2010, using two types of monovalent split virus vaccines: an AS03
      adjuvanted vaccine and a non-adjuvanted vaccine. We compared the reactogenicity
      of the vaccines in health professionals from a Clinical Research Institute in Rio
      de Janeiro, Brazil and there were no serious adverse events following
      immunization (AEFI) among the 494 subjects evaluated. The prevalence of any AEFI
      was higher in the AS03-adjuvanted vaccine at 2 h and 24 h post-vaccination [preva
      lence ratio (PR): 2.05, confidence interval (CI) 95%: 1.55-2.71, PR: 3.42, CI
      95%: 2.62-4.48, respectively]; however, there was no difference between the
      vaccines in the assessments conducted at seven and 21 days post-vaccination. The
      group receiving the AS03 post-adjuvanted vaccine had a higher frequency of local
      reactions at 2 h (PR: 3.01, CI 95%: 2.12-4.29), 24 h (PR: 4.57, CI 95%: 3.29
      6.37) and seven days (PR: 6.05, CI 95%: 2.98-12.28) post-vaccination. We
      concluded that the two types of vaccines caused no serious AEFI in the studied
      population and the adjuvanted vaccine was more reactogenic, particularly in the
      24 h following vaccination. This behaviour must be confirmed and better
      characterised by longitudinal studies in the general population.

PMID- 23147151
TI  - Wyeomyia exallos, a new species of sylvatic mosquito (Diptera: Culicidae) from
      Brazil.
AB  - Wyeomyia exallos, a new mosquito species from Atlantic Forest of southeastern
      Brazil, is described based on morphological characters of the adult female, male,
      male genitalia, pupa and fourth-instar larva. The morphological characters of Wy.
      exallos sp. nov. are compared with those of different subgenera of Wyeomyia as
      well as of species without subgeneric position. It is proposed that the new
      species should be placed in genus Wyeomyia Theobald without subgeneric
      assignment.

PMID- 23147152
TI  - Hepatitis E virus in liver and bile samples from slaughtered pigs of Brazil.
AB  - The objective of this study was to detect and identify hepatitis E virus (HEV)
      strains in liver and bile samples from slaughtered pigs in the state of Parana,
      Brazil. Liver and bile samples were collected from 118 asymptomatic adult pigs at
      a slaughterhouse in a major Brazilian pork production area. The samples were
      assayed using a nested reverse transcription-polymerase chain reaction protocol
      with primer sets targeting open reading frames (ORF)1 and 2 of the HEV genome.
      HEV RNA was detected in two (1.7%) liver samples and one (0.84%) bile sample
      using both primers sets. The HEV strains were classified as genotype 3b on the
      basis of their nucleotide sequences. These data suggest that healthy pigs may be
      a source of HEV infection for consumers of pig liver and slaughterhouse workers
      in Brazil.

PMID- 23147153
TI  - Dengue virus type 4 in Niteroi, Rio de Janeiro: the role of molecular techniques
      in laboratory diagnosis and entomological surveillance.
AB  - In Niteroi, state of Rio de Janeiro, dengue virus type 4 (DENV-4) was isolated
      for the first time in March 2011. We analysed the laboratory findings of the
      first cases and evaluated the use of molecular techniques for the detection of
      DENV-4 in Aedes aegypti that were field-caught. Conventional reverse
      transcriptase-polymerase chain reaction (RT-PCR) and SimplexaTM Dengue real-time
      RT-PCR confirmed DENV-4 infection in all cases. Additionally, DENV-4 was
      confirmed in a female Ae. aegypti with 1.08 x 10(3) copies/mL of virus, as
      determined by quantitative real-time RT-PCR. This is the first time the
      SimplexaTM Dengue real-time assay has been used for the classification of cases
      of infection and for entomological investigations. The use of these molecular
      techniques was shown to be important for the surveillance of dengue in humans and
      vectors.

PMID- 23147154
TI  - Differential in vitro activity of the DNA topoisomerase inhibitor idarubicin
      against Trypanosoma rangeli and Trypanosoma cruzi.
AB  - In this study the effect of eight DNA topoisomerase inhibitors on the growth
      Trypanosoma rangeli epimastigotes in cell culture was investigated. Among the
      eight compounds tested, idarubicin was the only compound that displayed promising
      trypanocidal activity with a half-maximal growth inhibition (GI(50)) value in the
      sub-micromolar range. Fluorescence-activated cell sorting analysis showed a
      reduction in DNA content in T. rangeli epimastigotes when treated with
      idarubicin. In contrast to T. rangeli, against Trypanosoma cruzi epimastigotes
      idarubicin was much less effective exhibiting a GI(50) value in the mid
      micromolar range. This result indicates that idarubicin displays differential
      toxic effects in T. rangeli and T. cruzi. Compared with African trypanosomes, it
      seems that American trypanosomes are generally less susceptible to DNA
      topoisomerase inhibitors.

PMID- 23147155
TI  - Use of the Kala-Azar Detect(r) and IT-LEISH(r) rapid tests for the diagnosis of
      visceral leishmaniasis in Brazil.
AB  - The performances of two rapid tests and a standard serological test for the
      diagnosis of visceral leishmaniasis (VL) were compared using sera from 193
      patients with VL and 85 controls. The Kala-Azar Detect((r)), IT-LEISH((r)) and
      IFI-LH((r)) assays showed sensitivities of 88.1%, 93.3% and 88.6%, respectively,
      and specificities of 90.6%, 96.5% and 80%, respectively. The sensitivity values
      were similar for both rapid tests, but the specificity and positive predictive
      values of IT-LEISH((r)) were higher than the corresponding values for IFI
      LH((r)). Both rapid tests showed satisfactory performances and can be used in
      primary health care settings; however, IT-LEISH((r)) permits the use of whole
      blood, making this assay more suitable for bedside diagnosis.

PMID- 23147156
TI  - The prevalence of human cytomegalovirus DNA in gliomas of Brazilian patients.
AB  - Members of the Herpesviridae family have been implicated in a number of tumours
      in humans. At least 75% of the human population has had contact with
      cytomegalovirus (HCMV). In this work, we screened 75 Brazilian glioma biopsies
      for the presence of HCMV DNA sequences. HCMV DNA was detected in 36% (27/75) of
      the biopsies. It is possible that HCMV could be a co-factor in the evolution of
      brain tumours.

PMID- 23147157
TI  - Species diversity of sandflies (Diptera: Psychodidae) during different seasons
      and in different environments in the district of Taquarucu, state of Tocantins,
      Brazil.
AB  - Phlebotomine sandflies are the vectors for the protozoan parasites that cause
      leishmaniasis. The present study investigated the species composition of sandfly
      fauna in the rural district of Taquarucu, municipality of Palmas, state of
      Tocantins, Brazil and compared the diversity of species among intradomicile,
      peridomicile and forest environments during the dry and rainy seasons. Sandflies
      were collected using CDC light traps over the course of three months during the
      dry and rainy seasons. A total of 767 specimens were captured, belonging to
      different 32 species. The most abundant species were Micropygomyia goiana
      (Martins, Falcao & Silva), Sciopemyia sordellii (Shannon & Del Ponte),
      Evandromyia carmelinoi (Ryan Fraiha, Lainson & Shaw), Evandromyia termitophila
      (Martins, Falcao & Silva), Nyssomyia whitmani (Antunes & Coutinho) and Lutzomyia
      longipalpis (Lutz & Neiva). The highest species diversity (30) and the greatest
      percentage of specimens (78.3%) were obtained during the rainy season. During the
      dry season, the species richness and abundance were greater in domestic
      environments. However, during the rainy season, the forest displayed the highest
      species richness and the domestic environment exhibited the greatest species
      abundance. Several important vector species are reported in this study.

PMID- 23147158
TI  - An immunoenzymatic assay for the diagnosis of hepatitis A utilising
      immunoglobulin Y.
AB  - The detection of anti-hepatitis A virus (HAV) antibody levels by diagnostic kits
      in the convalescent period of disease generally use immunoglobulin G (IgG), which
      is expensive. An alternative to IgG is immunoglobulin Y (IgY), an immunoglobulin
      antibody encountered in birds and reptiles. The aim of this study was to develop
      a competitive immunoenzymatic assay to measure total anti-HAV antibody levels
      using anti-HAV IgY as the capture and conjugated immunoglobulins. For this
      purpose, anti-HAV IgY was conjugated to horseradish peroxidase (HRP) and the
      optimal dilution of HRP-conjugated antibodies was evaluated to establish the
      competitive immuneenzymatic assay. The results obtained from our "in-house" assay
      were plotted on a receiver operator curve, which showed a sensitivity of 95% and
      a specificity of 98.8%, demonstrating that a competitive anti-HAV IgY
      immunoenzymatic assay developed "in house" could be used as an alternative to
      commercial assays that utilise IgG.

PMID- 23147160
TI  - Evolution of the incidence of chronic kidney disease Stage 5 requiring renal
      replacement therapy in the diabetic population of Catalonia.
AB  - BACKGROUND: Chronic kidney disease due to diabetes (DCKD) is the main known cause
      of renal replacement therapy (RRT) initiation. A Centers for Disease Control and
      Prevention study showed that the rate of DCKD cases initiating RRT among the
      overall DM population has dropped in the USA. Our main objective was to analyse
      this rate in Catalonia in 1994, 2002, 2006 and 2010. Cardiovascular risk factors
      (CVRF) in the diabetic population and characteristics and survival of DCKD
      patients on RRT were also evaluated. METHODS: Data from the Catalan Renal
      Registry was used to learn the number of DCKD cases on RRT together with their
      characteristics and survival rates. Data from the Catalonia Health Survey
      established the diabetic population and also the prevalence of CVRF in this
      population. RESULTS: The adjusted rate (95% CI) of patients initiating RRT with
      DCKD was 509.1 (484.6-533.7) pmp in 1994, 645.3 (621.6-669.0) in 2002, 602.6
      (581.4-623.9) in 2006 and 600.0 (578.4-621.6) in 2010. Survival of DCKD patients
      in the 4th year of RRT had increased progressively from 35.9% for DCKD cases
      versus 64.9% for CKD cases due to other causes in 1994, to 39.9% versus 58.3% in
      2002 and to 59.9% versus 65.9% in 2006. CONCLUSIONS: Since 2002, the rates of
      patients with DCKD initiating RRT among the overall DM population decreased
      slightly in Catalonia. Survival in these cases has increased progressively and in
      2006 is similar to the CKD patients due to other causes. This figure suggests a
      better overall management, especially of CVRF.

PMID- 23147161
TI  - Hepcidin-25 is related to cardiovascular events in chronic haemodialysis
      patients.
AB  - BACKGROUND: The development of atherosclerosis may be enhanced by iron
      accumulation in macrophages. Hepcidin-25 is a key regulator of iron homeostasis,
      which downregulates the cellular iron exporter ferroportin. In haemodialysis (HD)
      patients, hepcidin-25 levels are increased. Therefore, it is conceivable that
      hepcidin-25 is associated with all-cause mortality and/or fatal and non-fatal
      cardiovascular (CV) events in this patient group. The aim of the current analysis
      was to study the relationship between hepcidin-25 and all-cause mortality and
      both fatal and non-fatal CV events in chronic HD patients. METHODS: Data from 405
      chronic HD patients included in the CONvective TRAnsport STudy (NCT00205556) were
      studied (62% men, age 63.7 +/- 13.9 years [mean +/- SD]). The median (range)
      follow-up was 3.0 (0.8-6.6) years. Hepcidin-25 was measured with mass
      spectrometry. The relationship between hepcidin-25 and all-cause mortality or
      fatal and non-fatal CV events was investigated with multivariate Cox proportional
      hazard models. RESULTS: Median (interquartile range) hepcidin-25 level was 13.8
      (6.6-22.5) nmol/L. During follow-up, 158 (39%) patients died from any cause and
      131 (32%) had a CV event. Hepcidin-25 was associated with all-cause mortality in
      an unadjusted model [hazard ratio (HR) 1.14 per 10 nmol/L, 95% CI 1.03-1.26; P =
      0.01], but not after adjustment for all confounders including high-sensitive C
      reactive protein (HR 1.02 per 10 nmol/L, 95% CI 0.87-1.20; P = 0.80). At the same
      time, hepcidin-25 was significantly related to fatal and non-fatal CV events in a
      fully adjusted model (HR 1.24 per 10 nmol/L, 95% CI 1.05-1.46, P = 0.01).
      CONCLUSION: Hepcidin-25 was associated with fatal and non-fatal CV events, even
      after adjustment for inflammation. Furthermore, inflammation appears to be a
      significant confounder in the relation between hepcidin-25 and all-cause
      mortality. These findings suggest that hepcidin-25 might be a novel determinant
      of CV disease in chronic HD patients.

PMID- 23147162
TI  - The association of Klotho polymorphism with disease progression and mortality in
      IgA nephropathy.
AB  - BACKGROUNDS: IgA nephropathy (IgAN) is the most common primary glomerulonephritis
      causing end stage renal disease (ESRD), and vasculopathy is known to involve
      disease progression. Klotho, a gene related to aging, has been reported to play a
      role in atherosclerosis and endothelial dysfunction. We investigated whether
      klotho gene polymorphism affect clinical course of IgAN. METHODS: The data
      registered for PREMIER study which enrolled the patients with biopsy proven IgAN
      were analyzed. Two single nucleotide polymorphisms for klotho gene, G395A of
      promoter region and C1818T of exon 4, were examined, and investigated the
      association klotho genotypes with the progression of IgAN and patient survival.
      RESULTS: Clinical data from 973 patients confirmed about survival were analyzed.
      The allele frequency was 0.830 and 0.170 for allele G and A, and 0.816 and 0.184
      for allele C and T, which were complied with Hardy-Weinberg equilibrium (p=0.996
      and 0.531 respectively). Death was observed more frequently in A-allele carriers
      of G395A polymorphism (0.7 vs. 2.6 %, GG vs. GA+AA, p=0.022). Renal survival in
      Kaplan-Meier survival curve was also worse in same group (p=0.04). CONCLUSION:
      Klotho gene polymorphism was associated with patient survival and disease
      progression of IgAN.

PMID- 23147163
TI  - Migraine is not associated with enhanced atherosclerosis.
AB  - AIM: Migraine, in particular with aura, has been associated with an increased
      risk for ischemic stroke and coronary heart disease. The underlying mechanism is
      unknown. In a cross-sectional case control study we investigated whether an
      enhanced risk of atherosclerosis in migraineurs explains this increased
      cardiovascular risk. METHODS: Subjects were participants from the population
      based Erasmus Rucphen Family study. Atherosclerosis was assessed in 360
      migraineurs (209 without aura and 151 with aura) and 617 subjects without
      migraine or severe headache. Atherosclerosis was quantified by intima media
      thickness, pulse wave velocity and ankle-brachial index. RESULTS: Migraineurs,
      especially with aura, were found more likely to smoke, have diabetes or a
      modestly decreased HDL-cholesterol. No differences were found for the
      atherosclerosis parameters. CONCLUSION: In this large population-based study,
      migraineurs have no increased risk of atherosclerosis. Therefore, enhanced
      atherosclerosis is an unlikely explanation for the increased cardiovascular risk
      seen in migraineurs.

PMID- 23147165
TI  - Anterior maxillary and mandibular biotype:  relationship between gingival
      thickness and width with respect to underlying bone thickness.
AB  - PURPOSE: : Periodontal biotype is considered to be a significant factor related
      to successful dental treatments. The purpose of this study was to determine the
      relationship between gingival thickness (GT) and width with respect to the
      underlying bone thickness in the maxillary and mandibular anterior sextant.
      MATERIALS AND METHODS: : Overall, 180 anterior teeth within healthy patients were
      assessed. GT and buccal bone thickness (BT) were measured at 3 locations:
      crestal/gingival margin, tooth apex, and a midpoint between the 2. In addition,
      the apicoincisal gingival width (GW) was recorded. Clinical and cone beam CT
      measurements were compared and correlated. RESULTS: : No statistically
      significant relations were observed between GT and BT measures at any of the 3
      positions. The mean GT at crestal mid and apical position for the maxillary teeth
      was 1.01 (+/-0.58) mm, 1.06 (+/-0.48) mm, and 0.83 (+/-0.47) mm, respectively,
      and the corresponding mean BT was 1.24 (+/-0.90) mm, 0.81 (+/-0.33) mm, and 2.78
      (+/-1.62) mm, respectively. The GW is directly related (R = 0.007; P < 0.05) to
      the crestal BT. CONCLUSION: : In this study, the GT is not linked to the BT.
      However, the GW seems to be associated with the crestal BT.

PMID- 23147166
TI  - Identification of the mental neurovascular bundle:  a comparative study of
      panoramic radiography and computer tomography.
AB  - OBJECTIVES: To compare the images of the mental canal in panoramic radiography
      (PR) and computed tomography (CT) by analyzing the concordance with diagnostic
      tests and examiners. MATERIAL AND METHODS: The position of the mental foramen
      (MF), distance to the lower mandibular border, anterior length of the mental loop
      (ML), agreement between examiners and diagnostic concordance were registered in
      50PR and 50CT. RESULTS: ML was identified (34.5/41%, PR/CT). PR magnification was
      36.6% higher than in CT. The anterior extension and distance to the inferior
      border of the MF was higher for PR (2-6.2 mm). Inter-examiner agreement on CT was
      good (kappa = 0.628) and very good on PR (kappa = 0.845). CONCLUSION: There is a
      magnification (36.6%) of the images in PR with respect to the CT. Identification
      of MF and ML is not related to the bone quality. Inter-examiner agreement is
      better on PR.

PMID- 23147164
TI  - The locus of flicker adaptation in the migraine visual system: a dichoptic study.
AB  - BACKGROUND: Flickering light has been shown to sensitize the migraine visual
      system at high stimulus contrast while elevating thresholds at low contrast. The
      present study employs a dichoptic psychophysical paradigm to ask whether the
      abnormal adaptation to flicker in migraine occurs before or after the binocular
      combination of inputs from the two eyes in the visual cortex. METHODS: Following
      adaptation to high contrast flicker presented to one eye only, flicker contrast
      increment thresholds were measured in each eye separately using dichoptic
      viewing. RESULTS: Modest interocular transfer of adaptation was seen in both
      migraine and control groups at low contrast. Sensitization at high contrast in
      migraine relative to control participants was seen in the adapted eye only, and
      an unanticipated threshold elevation occurred in the non-adapted eye. Migraineurs
      also showed significantly lower aversion thresholds to full field flicker than
      control participants, but aversion scores and increment thresholds were not
      correlated. CONCLUSIONS: The results are simulated with a three-stage neural
      model of adaptation that points to strong adaptation at monocular sites prior to
      binocular combination, and weaker adaptation at the level of cortical binocular
      neurons. The sensitization at high contrast in migraine is proposed to result
      from stronger adaptation of inhibitory neurons, which act as a monocular
      normalization pool.

PMID- 23147167
TI  - Engineering of human-type O-glycosylation in Nicotiana benthamiana plants.
AB  - Therapeutic properties of recombinant proteins are very often affected by the
      composition and heterogeneity of their glycans. Conventional expression systems
      for recombinant pharmaceutical proteins typically do not address this problem and
      produce a mixture of glycoforms that are neither identical to human glycans nor
      optimized for enhanced efficacy. In terms of glycosylation, plants offer certain
      advantages over mammalian cells as the N-glycosylation pathway of plants is
      comparably simple and a typical mammalian O-glycosylation pathway is not present
      at all. During the last ten years we have developed a plant-based expression
      platform for the generation of recombinant glycoproteins with defined N-glycans.
      Now we have extended our tool-box for glyco-engineering in the tobacco related
      species Nicotiana benthamiana toward the production of tailored mucin-type O
      glycans on recombinant proteins. 

PMID- 23147168
TI  - Production of biopharmaceutical proteins by yeast: advances through metabolic
      engineering.
AB  - Production of recombinant proteins for use as pharmaceuticals, so-called
      biopharmaceuticals, is a multi-billion dollar industry. Many different cell
      factories are used for the production of biopharmaceuticals, but the yeast
      Saccharomyces cerevisiae is an important cell factory as it is used for
      production of several large volume products. Insulin and insulin analogs are by
      far the dominating biopharmaceuticals produced by yeast, and this will increase
      as the global insulin market is expected to grow from USD12B in 2011 to more than
      USD32B by 2018. Other important biopharmaceuticals produced by yeast are human
      serum albumin, hepatitis vaccines and virus like particles used for vaccination
      against human papillomavirus. Here is given a brief overview of biopharmaceutical
      production by yeast and it is discussed how the secretory pathway can be
      engineered to ensure more efficient protein production. The involvement of
      directed metabolic engineering through the integration of tools from genetic
      engineering, systems biology and mathematical modeling, is also discussed. 

PMID- 23147169
TI  - Clinical aspects and molecular genetics of persistent mullerian duct syndrome
      associated with transverse testicular ectopia: report of three cases.
AB  - Persistent mullerian duct syndrome (PMDS) is a rare form of male
      pseudohermaphroditism, characterized by the presence of a uterus and fallopian
      tubes owing to failure of mullerian duct regression in genotypically normal
      males. The association between a persistent mullerian duct and transverse
      testicular ectopia (TTE) is even more uncommon. PMDS with TTE is a very rare
      pathological association, often discovered during repair for inguinal hernia or
      cryptorchidism. We report 3 cases of Chinese patients with PMDS associated with
      TTE. Hysterectomy was performed, with resection of the underdeveloped fallopian
      tubes. Both gonads were placed into subdartos pouches in each scrotum by the
      transseptal approach. PMDS with TTE is a rarely encountered form of male
      pseudohermaphroditism usually unexpectedly found at surgery for cryptorchidism or
      inguinal hernia. Surgical treatment should avoid damage of fertile testes and
      vasa deferens.

PMID- 23147170
TI  - Yeast screens for host factors in positive-strand RNA virus replication based on
      a library of temperature-sensitive mutants.
AB  - RNA viruses exploit host cells by altering cellular pathways, recruiting host
      factors, remodeling intracellular membranes and escaping host antiviral
      responses. Model hosts, such as Saccharomyces cerevisiae (yeast), are valuable to
      identify host factors involved in viral RNA replication. The many advantages of
      using yeast include the availability of various yeast mutant libraries, such as
      (i) single gene-deletion library; (ii) the essential gene library (yTHC); and
      (iii) the yeast ORF over-expression library. Here, we have used a novel
      temperature-sensitive (ts) mutant library of essential yeast genes to identify
      118 host proteins affecting replication of Tomato bushy stunt virus, in yeast
      model host. Testing 787 ts mutants led to the identification of host factors, of
      which 72 proteins facilitated TBSV replication in yeast and 46 proteins were
      inhibitory. Altogether, ~85% of the identified proteins are novel host factors
      affecting tombusvirus replication. The ts mutant library screen also led to the
      identification of 17 essential genes, which have been documented before, thus
      confirming the importance of these genomic screens. Overall, we show the power of
      ts mutant library in identification of host factors for RNA virus replication.

PMID- 23147171
TI  - [58-year-old woman with fatigue, adynamia and night sweat].

PMID- 23147173
TI  - Impact of a high loading dose of atorvastatin on contrast-induced acute kidney
      injury.
AB  - BACKGROUND: The role of statins in the prevention of contrast-induced acute
      kidney injury (CIAKI) is controversial. METHODS AND RESULTS: First, we
      investigated the in vivo effects of atorvastatin on CIAKI. Patients with chronic
      kidney disease enrolled in the Novel Approaches for Preventing or Limiting Events
      (NAPLES) II trial were randomly assigned to (1) the atorvastatin group (80 mg
      within 24 hours before contrast media [CM] exposure; n=202) or (2) the control
      group (n=208). All patients received a high dose of N-acetylcysteine and sodium
      bicarbonate solution. Second, we investigated the in vitro effects of
      atorvastatin pretreatment on CM-mediated modifications of intracellular pathways
      leading to apoptosis or survival in renal tubular cells. CIAKI (ie, an increase
      >10% of serum cystatin C concentration within 24 hours after CM exposure)
      occurred in 9 of 202 patients in the atorvastatin group (4.5%) and in 37 of 208
      patients in the control group (17.8%) (P=0.005; odds ratio=0.22; 95% confidence
      interval, 0.07-0.69). CIAKI rate was lower in the atorvastatin group in both
      diabetics and nondiabetics and in patients with moderate chronic kidney disease
      (estimated glomerular filtration rate, 31-60 mL/min per 1.73 m(2)). In the in
      vitro model, pretreatment with atorvastatin (1) prevented CM-induced renal cell
      apoptosis by reducing stress kinases activation and (2) restored the survival
      signals (mediated by Akt and ERK pathways). CONCLUSIONS: A single high loading
      dose of atorvastatin administered within 24 hours before CM exposure is effective
      in reducing the rate of CIAKI. This beneficial effect is observed only in
      patients at low to medium risk.

PMID- 23147172
TI  - Age, sex, and hypertension-related remodeling influences left ventricular torsion
      assessed by tagged cardiac magnetic resonance in asymptomatic individuals: the
      multi-ethnic study of atherosclerosis.
AB  - BACKGROUND: The aim of the present study was to evaluate how torsion is
      influenced by left ventricular (LV) remodeling associated with age, sex, and
      hypertension in a large community-based population. METHODS AND RESULTS:
      Myocardial shortening and torsion were assessed by tagged cardiac magnetic
      resonance in 1478 participants without clinically apparent cardiovascular disease
      in the Multi-Ethnic Study of Atherosclerosis (MESA). Torsion was defined as the
      difference between apical and basal rotation divided by slice distance. In
      multivariable linear regression models, older age was associated with lower
      stroke volume (-3.6 mL per decade; P<0.001) and higher LV mass-to-volume ratio
      (0.03 g/mL per decade; P<0.001), along with lower circumferential shortening (
      0.17% per decade; P<0.05). Torsion, however, was greater at older ages (0.14
      degrees  per decade; P<0.001) and in women (0.37 degrees /cm versus men;
      P<0.001). Hypertensive participants had higher LV mass and LV mass-to-volume
      ratio (15.5 g and 0.07 g/mL, respectively; P<0.001 for both). Circumferential
      shortening was lower in hypertensive (-0.42%; P<0.01), whereas torsion was higher
      after adjustment for age and sex (0.17 degrees /cm; P<0.05). CONCLUSIONS: Older
      age is associated with lower LV volumes and greater relative wall thickness and
      is accompanied by lower circumferential myocardial shortening, whereas torsion is
      greater with older age. Hypertensive individuals have greater LV volumes and
      relative wall thickness and lower circumferential shortening. Torsion, however,
      is greater in hypertension independently of age and sex. Torsion may therefore
      represent a compensatory mechanism to maintain an adequate stroke volume and
      cardiac output in the face of the progressively reduced LV volumes and myocardial
      shortening associated with hypertension and aging.

PMID- 23147174
TI  - Transarterial embolization in children with blunt splenic injury results in
      postembolization syndrome: a matched case-control study.
AB  - BACKGROUND: Postembolization syndrome (PES) has been reported in adults following
      transarterial embolization (TAE) for blunt splenic injury (BSI), but not in
      children. We report the incidence of PES in a group of children who underwent
      TAE. METHODS: Children who underwent TAE were identified, and each case of TAE
      was matched by grade of splenic injury and Injury Severity Score with four
      similar patients who did not. Data collected included demographics, vital signs,
      laboratory data, the presence of contrast blush, the hemoperitoneum score,
      hospital course, and outcome. The subgroup with a high hemoperitoneum score was
      analyzed separately. RESULTS: Within 12 years, of 448 patients diagnosed as
      having BSI, 11 (2.5%) underwent TAE. Children undergoing TAE had lower
      preprocedure hemoglobin (10.4 vs. 11.8 g/dL, p = 0.02) and platelet counts (194.8
      vs. 267.9 cells/MUL, p = 0.006) and received more packed red blood cells (3.1 vs.
      0.11 units, p < 0.001) and fresh-frozen plasma (0.24 vs. 0 units, p = 0.04).
      Postprocedure hemoglobin and platelet counts were not different, but white blood
      cell count was elevated in the TAE group (13.5 vs. 9.1 cells/MUL, p = 0.04). The
      TAE group had longer intensive care unit (2.82 vs. 1.18 days, p < 0.001) and
      hospital (8.6 vs. 5.2 days, p < 0.001) stays and took longer to tolerate a full
      diet (5.4 vs. 1.6 days, p < 0.001). These relationships persisted when only
      children with high hemoperitoneum scores were considered.PES occurred in 90.1% of
      those who underwent TAE and in 2.3% of those who did not. Late complications were
      noted in 27.3% of the TAE group versus none and correlated with the length of
      hospital stay (10.67 vs. 5.63 days, p < 0.001). CONCLUSION: TAE is a valuable
      tool in the management of BSI in children but leads to PES in most children. PES
      is self-limited but is associated with longer hospital stays and more
      complications and readmissions, with no effect on operative rate or mortality.
      LEVEL OF EVIDENCE: Prognostic study, level III; therapeutic study, level IV.

PMID- 23147175
TI  - Compartment syndrome performance improvement project is associated with increased
      combat casualty survival.
AB  - BACKGROUND: In 2008, we showed that incomplete or delayed extremity fasciotomies
      were associated with mortality and muscle necrosis in war casualties with limb
      injury. Subsequently, we developed an education program focused on surgeon
      knowledge gaps regarding the diagnosis of compartment syndrome and prophylactic
      fasciotomy. The program included educational alerts, classroom training, video
      instruction, and a research publication. We compared casualty data before and
      after the program implementation to determine whether the education altered
      outcomes. METHODS: Similar to the previous study, a case series was made from
      combat casualty medical records. Casualties were US military servicemen with
      fasciotomies performed in Iraq, Afghanistan, or Germany between two periods
      (periods 1 and 2). RESULTS: In both periods, casualty demographics were similar.
      Most fasciotomies were performed to the lower leg and forearm. Period 1 had 336
      casualties with 643 fasciotomies, whereas Period 2 had 268 casualties with 1,221
      fasciotomies (1.9 vs. 4.6 fasciotomies per casualty, respectively; p < 0.0001).
      The mortality rate decreased in Period 2 (3%, 8 of 268 casualties) from Period 1
      (8%, 26 of 336 casualties; p = 0.0125). Muscle excision and major amputation
      rates were similar in both periods (p > 0.05). Rates of casualties with revision
      fasciotomy decreased to 8% in Period 2, (22 of 268 casualties) versus 15% in
      Period 1 (51 of 336 casualties; p = 0.009). CONCLUSION: Combat casualty care
      following implementation of a fasciotomy education program was associated with
      improved survival, higher fasciotomy rates, and fewer revisions. Because delayed
      fasciotomy rates were unchanged, further effort to educate providers may be
      indicated. LEVEL OF EVIDENCE: Therapeutic study, level IV.

PMID- 23147177
TI  - Repeated computed tomographic scans in transferred trauma patients:  Indications,
      costs, and radiation exposure.
AB  - BACKGROUND: Trauma patients are often transferred to regional Level I trauma
      centers from other institutions. At times, when the patient presents to the
      trauma center, radiologic studies performed at the previous institution are
      repeated. The aim of this study was to assess the proportion of computed
      tomographic (CT) scans repeated in trauma patients receiving CT scans before
      transfer and to obtain the indications for these repeats. This study also
      estimated the additional radiation dose and economic burden associated with
      repeated CT scans. METHODS: This prospective, observational cohort study
      collected data consecutively on transferred trauma patients who had received a CT
      scan at the transferring institution and investigated whether the CT scan was
      repeated at the receiving institution. Indications for repeating CT scans were
      obtained from the general surgery trauma service. The economic impacts were
      assessed using fee schedules from the hospital and the Center of Medicare and
      Medicaid Services. Effective dose radiation was estimated using the dose-length
      product method. RESULTS: Of the 211 patients who presented with a previous CT
      scan at the transferring institution, 82 had at least one repeated CT scan.
      Indications for repeating CT scans varied based on the body region. Additional
      hospital charges ranged from $728 to $5,892 with an average of $1,762.40 for
      patients having one or more repeated CT scans. The estimated additional effective
      dose radiation ranged from 1.2 mSv to 124 mSv with an average of 21.5 mSv.
      CONCLUSION: This study reveals the high rates of repeated CT scans in transferred
      trauma patients and the various indications that lead to them. Additional
      hospital charges and additional low levels of radiation exposure are a
      consequence of these repeats. LEVEL OF EVIDENCE: Diagnostic study, level IV.

PMID- 23147178
TI  - Insurance-and race-related disparities decrease in elderly trauma patients.
AB  - BACKGROUND: Little focus is on health care disparities in the elderly, a
      population largely covered by public insurance. We characterized insurance type
      and race in elderly trauma patients to determine if lack of insurance or minority
      status predict increased mortality. METHODS: The National Trauma Data Bank
      (version 7.0) was queried for all adult blunt trauma patients. We divided
      patients into two cohorts (15-64 or >= 65 years) based on age for universal
      Medicare eligibility. Our primary outcome measure was in-hospital mortality.
      Multiple logistic regression was used to control for confounding variables.
      RESULTS: A total of 541,471 patients met inclusion criteria. Among younger
      patients, the most common insurance type was private (41.0%), with 26.9%
      uninsured. In contrast, the most common insurance type among older patients was
      Medicare (64.6%), with 6.0% uninsured. Within the younger cohort, private
      insurance (adjusted odds ratio [AOR], 0.6; p < 0.01) and other insurance (AOR,
      0.8; p < 0.01) predicted reduced mortality, while Medicare predicted similar
      mortality (AOR, 1.1; p = 0.18) compared with no insurance. Black race (AOR, 1.4;
      p < 0.01) and Hispanic ethnicity (AOR, 1.4; p < 0.01) predicted higher mortality
      compared with white race. Within the older cohort, no insurance predicted similar
      mortality as Medicare (AOR, 1.0; p = 0.43), private insurance (AOR, 1.0; p =
      0.51), and other insurance (AOR, 1.0; p = 0.71). Hispanic ethnicity predicted
      increased mortality (AOR, 1.4; p < 0.01), while Asian race was protective (AOR,
      0.7; p = 0.01) compared with white race. CONCLUSION: Elderly trauma patients
      present primarily with Medicare, while younger trauma patients are mostly
      privately insured; elderly patients are four times more likely to be insured.
      Disparities caused by lack of insurance and minority race are reduced in elderly
      trauma patients. LEVEL OF EVIDENCE: Epidemiologic/prognostic study, level III.

PMID- 23147176
TI  - Hypertonic saline resuscitation enhances blood pressure recovery and decreases
      organ injury following hemorrhage in acute alcohol intoxicated rodents.
AB  - BACKGROUND: Acute alcohol intoxication (AAI) impairs the hemodynamic and arginine
      vasopressin (AVP) counter-regulation to hemorrhagic shock (HS) and lactated
      Ringer's solution (LR) fluid resuscitation (FR). The mechanism of AAI-induced
      suppression of AVP release in response to HS involves accentuated nitric oxide
      (NO) inhibitory tone. In contrast, AAI does not prevent AVP response to increased
      osmolarity produced by hypertonic saline (HTS) infusion. We hypothesized that FR
      with HTS during AAI would enhance AVP release by decreasing periventricular
      nucleus NO inhibitory tone, subsequently improving mean arterial blood pressure
      (MABP) and organ perfusion. METHODS: Male Sprague-Dawley rats received a 15-hour
      alcohol infusion (2.5 g/kg + 0.3 g/kg/h) or dextrose (DEX) before HS (40 mm Hg *
      60 minutes) and FR with HTS (7.5%, 4 ml/kg) or LR (2.4 * blood volume removed).
      Organ blood flow was determined, and brains were collected for NO content at 2
      hours after FR. RESULTS: HTS improved MABP recovery in AAI (109 vs. 80 mm Hg) and
      DEX (114 vs. 83 mm Hg) animals compared with LR. This was associated with higher
      (>60%) circulating AVP levels at 2 hours after FR compared with those detected in
      LR animals in both groups. Neither AAI alone nor HS in DEX animals resuscitated
      with LR altered organ blood flow. In AAI animals, HS and FR with LR reduced blood
      flow to the liver (72%), small intestine (65%), and large intestine (67%)
      compared with shams. FR with HTS improved liver (threefold) and small intestine
      (twofold) blood flow compared with LR in AAI-HS animals. The enhanced MABP
      response to HTS was prevented by pretreatment with a systemic AVP V1a receptor
      antagonist. HTS decreased periventricular nucleus NO content in both groups 2
      hours after FR. CONCLUSION: These results suggest that FR with HTS in AAI results
      in the removal of central NO inhibition of AVP, restoring AVP levels and
      improving MABP and organ perfusion in AAI-HS.

PMID- 23147179
TI  - The lost to trauma patient follow-up: a system or patient problem.
AB  - BACKGROUND: The objective of this study was to explore the reasons for trauma
      patients' failure to follow up at a trauma clinic (TC). METHODS: A 1-year
      retrospective analysis was conducted on those trauma services patients (n = 799)
      who were discharged from Parkview Hospital in 2009. Hospital electronic medical
      records were examined to identify variables of interest; telephone interviews
      were attempted on those patients who failed to follow up (FTF); and calls were
      made to the offices of involved subspecialist (SS) to determine if any follow-up
      had occurred. Data analysis was performed by Microsoft Excel and SPSS. RESULTS:
      Two hundred thirty-three patients were identified as having FTF in the TC.
      Patient or external factors caused a follow-up loss for 147 patients (63.1%), and
      44% of them did have a follow-up with an SS. Hospital or internal factors
      resulted in 86 patients (36.9%) being FTF, and 43% of them were seen by an SS.
      The physician compliance rate per policy was 89.2% (713 of 799). The patient
      compliance rate at TC follow-up was 79.3% (566 of 713). The total patient
      compliance rate both at the TC and SS follow-up was 87.2% (669 of 767). No
      significant demographic differences in age, sex, Injury Severity Scores, hospital
      payment status, or distance from the hospital were noted between those patients
      who had FTF in the external or internal factor groups. Of the 130 patients who
      had no follow-up, 39% did meet follow-up criteria. CONCLUSION: Only 10.8% of the
      trauma patients who had appointments for any posttrauma follow-up had FTF,
      implying that the patient is not the reason for FTF but that FTF is a system
      issue. With improved patient education on the day of hospital discharge and
      improved physician discharge orders, trauma patient follow-up could approach
      100%. LEVEL OF EVIDENCE: Epidemiologic study, level III.

PMID- 23147180
TI  - Changes of lymph metabolites in a rat model of sepsis induced by cecal ligation
      and puncture.
AB  - BACKGROUND: Sepsis is a clinical syndrome defined by a systemic response to
      infection and remains a prevalent clinical challenge. The underlying
      pathophysiology of sepsis is poorly understood. Using a metabolomic method, the
      present study observed changes in lymph composition during sepsis in a septic
      model in an attempt to find out new biomarkers for the early diagnosis and
      treatment of sepsis. METHODS: Adult male Sprague-Dawley rats underwent cecal
      ligation and puncture. Blood samples were obtained via the lateral caudal vein,
      and lymph was obtained from the thoracic duct. Cytokines were measured in plasma
      and lymph samples by enzyme-linked immunosorbent assay at different time points
      after cecal ligation and puncture. Rat lymph samples were analyzed by high
      performance liquid chromatography-quadrupole time-of-flight mass spectrometry.
      Multivariate analysis was used to profile potential biomarkers in rat septic
      lymph samples. RESULTS: Plasma and lymph tumor necrosis factor alpha, interleukin
      1beta, and interleukin 6 levels were elevated in septic group as compared with
      the control. Of the 10 characteristic metabolites identified in the septic model,
      six (palmitoyl-L-carnitine, creatinine, phenylalanine, isonicotinic acid,
      choline, and 5-azacytidine) were high, and four (1-O-Hexadecyl-2-lyso-glycero-3
      phosphorylcholine, alanine, 4-amino-5-hydroxymethyl-2-methylpyrimidine, and
      asymmetric dimethylarginine) were low. CONCLUSION: These biomarkers were mainly
      involved in energy metabolism and vascular tone and may prove beneficial to
      distinguish sepsis from other inflammatory conditions or predict outcomes.

PMID- 23147181
TI  - Autologous transplantation of endothelial progenitor cells to prevent multiple
      organ dysfunction syndromes in pig.
AB  - BACKGROUND: It was observed that the number and function of endothelial
      progenitor cells (EPCs) decreased sharply in the progression of multiple organ
      dysfunction syndrome (MODS), and it may be the main pathogenesis for MODS. We aim
      to perform autologous transplantation of EPCs on animal models of MODS to
      investigate whether EPCs might be used to prevent MODS caused by severe sepsis.
      METHODS: A total of 60 pigs were randomly divided into three groups: subjected to
      hemorrhagic shock + resuscitation + endotoxemia only (MODS group); performed
      autologous transplantation of EPCs after hemorrhagic shock + resuscitation +
      endotoxemia (transplantation group); and control group. Mononuclear cells of
      animals of the transplantation group were isolated by density-gradient
      centrifugation for ex vivo expansion, and the six-passage EPCs labeled with 5
      carboxyfluorescein diacetate succinimidyl ester were autologously transplanted at
      a density of 1 * 10(7) cells/kg body weight at the 24th hour after endotoxemia.
      The function of important organs was monitored continuously to assess the effects
      of autologous transplantation of EPCs on MODS. RESULTS: All animals of the MODS
      group developed MODS (100%), and 17 (85%) of 20 animals died because of MODS; the
      incidence of MODS and mortality rate in the transplantation group were 45% (9 of
      20 pigs; p < 0.01) and 35% (7 of 20 pigs; p < 0.01). In transplantation group,
      the incidence of pulmonary dysfunction, cardiac dysfunction, hepatosis, and renal
      dysfunction were 40%, 10%, 5%, and 15%, respectively. The capillary densities of
      important organs, including the heart, liver, kidney, intestine, and lung, after
      autologous transplantation of EPCs were significantly higher than those in the
      MODS group (p < 0.01). CONCLUSION: Autologous transplantation of EPCs could
      migrate to injured organs and induce angiogenesis to restore blood flow that
      could improve the function of important organs. It could prevent the incidence of
      MODS and reduce mortality rate caused by trauma and severe sepsis. Autologous
      transplantation of EPCs would be a novel, cell-based, vascular endothelium
      targeted therapeutic strategy for MODS.

PMID- 23147182
TI  - Pediatric orthopedic injuries following an earthquake: experience in an acute
      phase field hospital.
AB  - BACKGROUND: Following the 2010 earthquake in Haiti, the Israel Defense Forces
      Medical Corps deployed a field hospital in Port au Prince. The purpose of this
      study was to characterize the injuries sustained by the pediatric population
      treated in the hospital and examine the implications for planning deployment in
      future similar disasters. METHODS: Medical records of children treated in the
      hospital were reviewed and compared with medical records of the adult population.
      RESULTS: A total of 1,111 patients were treated in the hospital. Thirty-seven
      percent were aged 0 to 18 years. Earthquake-related injuries were the cause of
      admission in 47% of children and 66% of adults. Forty-seven percent of children
      with traumatic injuries sustained fractures. Seventy-two percent were in the
      lower limbs, 19% were in the upper limbs, and 9% were in the axial skeleton, with
      the femur being the most common long bone fractured compared with the tibia in
      adults.There were four functional operating theaters, and treatment guidelines
      were adjusted to the rapidly changing situation. Soft tissue injuries were
      treated by aggressive debridement. Fractures were stabilized by external fixation
      or casting. Amputation was performed only for nonviable limbs or life-threatening
      sepsis. Children were more likely than adults to undergo surgery (44% vs. 29% of
      trauma patients). To maximize hospital surge capacity, minor procedures were
      performed in the wards under sedation, and patients were discharged after an
      average of 1.4 days, with subsequent follow-up in the clinic. CONCLUSION:
      Children constitute a high percentage of patients in a developing country. The
      epidemiology of pediatric injuries following an earthquake differs significantly
      from that encountered in everyday practice and compared with that in adults.
      Children sustain a significantly higher percentage of femoral fractures and are
      more likely to require surgery. The shift to nontraumatic reasons for admission
      occurred earlier in the pediatric population than in adults. Organizations
      providing post-earthquake relief are usually geared toward adult populations and
      will require supplementation of both manpower and equipment specifically suited
      for treatment of pediatric patients. Early deployment teams should be adequately
      staffed with adult and pediatric orthopedists. LEVEL OF EVIDENCE: Epidemiologic
      study, level IV.

PMID- 23147183
TI  - Impact of adaptive statistical iterative reconstruction on radiation dose in
      evaluation of trauma patients.
AB  - BACKGROUND: A recent study showed that computed tomographic (CT) scans
      contributed 93% of radiation exposure of 177 patients admitted to our Level I
      trauma center. Adaptive statistical iterative reconstruction (ASIR) is an
      algorithm that reduces the noise level in reconstructed images and therefore
      allows the use of less ionizing radiation during CT scans without significantly
      affecting image quality. ASIR was instituted on all CT scans performed on trauma
      patients in June 2009. Our objective was to determine if implementation of ASIR
      reduced radiation dose without compromising patient outcomes. METHODS: We
      identified 300 patients activating the trauma system before and after the
      implementation of ASIR imaging. After applying inclusion criteria, 245 charts
      were reviewed. Baseline demographics, presenting characteristics, number of
      delayed diagnoses, and missed injuries were recorded. The postexamination volume
      CT dose index (CTDIvol) and dose-length product (DLP) reported by the scanner for
      CT scans of the chest, abdomen, and pelvis and CT scans of the brain and cervical
      spine were recorded. Subjective image quality was compared between the two
      groups. RESULTS: For CT scans of the chest, abdomen, and pelvis, the mean CTDIvol
      (17.1 mGy vs. 14.2 mGy; p < 0.001) and DLP (1,165 mGy.cm vs. 1,004 mGy.cm; p <
      0.001) was lower for studies performed with ASIR. For CT scans of the brain and
      cervical spine, the mean CTDIvol (61.7 mGy vs. 49.6 mGy; p < 0.001) and DLP
      (1,327 mGy.cm vs. 1,067 mGy.cm; p < 0.001) was lower for studies performed with
      ASIR. There was no subjective difference in image quality between ASIR and non
      ASIR scans. All CT scans were deemed of good or excellent image quality. There
      were no delayed diagnoses or missed injuries related to CT scanning identified in
      either group. CONCLUSION: Implementation of ASIR imaging for CT scans performed
      on trauma patients led to a nearly 20% reduction in ionizing radiation without
      compromising outcomes or image quality. LEVEL OF EVIDENCE: Therapeutic study,
      level IV.

PMID- 23147184
TI  - Patterns of structural head injury in children younger than 3 years: a ten-year
      review of 519 patients.
AB  - BACKGROUND: Abusive head injury is a major contributor to morbidity and mortality
      in infants and toddlers, but data comparing patterns of injury in corroborated
      accidental trauma and confessed child abuse are scarce. METHODS: This is a
      retrospective review of head injuries with abnormal neuroimaging in children
      younger than 3 years during a 10-year period in Auckland, New Zealand. Histories
      were assumed to be true. Results were analyzed for incongruity then compared with
      data on confessed abuse and corroborated accidental injury. RESULTS: Five hundred
      nineteen cases were analyzed. Most cases were congruent with the history, and
      their pattern was consistent with the literature on accidental head trauma in
      childhood. However, a spike of subdural hemorrhage was seen in the first 6 months
      of life, explained neither by mechanism nor by published data on birth trauma.
      The age distribution of retinal hemorrhage was also inconsistent with published
      data on birth trauma. In infants younger than 6 months, retinal and subdural
      hemorrhages were associated with the absence of a history of trauma. In older
      children (6 months-3 years), subdural hemorrhage was more common after minor
      falls (<1 m, 49%) than major falls (>2 m, 20%) (p = 0.002). CONCLUSION: We
      conclude that when a young child (particularly an infant younger than 6 months)
      presents with traumatic intracranial pathology and either no history of trauma or
      a history of a minor fall, it must be seriously considered that the history is
      false. LEVEL OF EVIDENCE: Epidemiologic study, level III.

PMID- 23147185
TI  - Quality of life one year after a road accident: results from the adult ESPARR
      cohort.
AB  - BACKGROUND: There are a few studies assessing repercussions in road accident
      victims, which reported their results in quality of life (QoL), on an
      epidemiologic point of view. METHODS: ESPARR (follow-up of victims of road
      accident in the Rhone) is a prospective cohort study of 1,168 individuals (age >=
      16 years) involved in road traffic accidents, having been admitted to one of the
      hospitals in the Rhone departement (France). The World Health Organization
      Quality of Life Questionnaire-Brief Version (WHOQOL-Bref) was used to assess QoL
      at the 1-year follow-up. chi(2) analysis was performed to test differences
      between groups, logistic regression was performed to examine predictors of global
      QoL and health, and linear regression was performed to examine predictors of the
      four functioning domains of the WHOQOL-Bref. RESULTS: Lesion severity (New Injury
      Severity Index >= 16; odds ratio, 2.6; 95% confidence interval, 1.7-3.9) and
      presence of head lesions (odds ratio, 1.5; 95% confidence interval, 1.1-2.2) were
      predictive of unsatisfactory QoL. Female sex, educational level lower than school
      graduation, severe injury, intention to lodge a complaint, early postaccident
      medical complications were predictive of health dissatisfaction. Several factors
      seemed to be associated to a poor QoL; notably, posttraumatic stress disorder was
      associated with low scores in all four WHOQOL-Bref domains. Socioeconomic factors
      were also significant, notably financial problems. CONCLUSION: The strong points
      of the present study lie in the fact that it is based on a representative cohort
      of road accident victims in an area in which all those treated within the
      hospital system after a road accident have been registered. The present study
      shows the strong correlation between QoL and posttraumatic stress disorder. LEVEL
      OF EVIDENCE: Prognostic study, level II.

PMID- 23147186
TI  - Attitudes and acceptance of First Person Authorization: a national comparison of
      donor and nondonor families.
AB  - BACKGROUND: First Person Authorization (i.e., donor designation) legislation
      makes indicating one's intent to be a posthumous organ donor legally binding,
      much like a living will or advance directive. Such legislation is the most recent
      in a long history of organ donation policies in the United States and has
      received little attention in the literature. METHODS: This retrospective cohort
      study recruited nine US organ procurement organizations (OPOs) and their staff
      who make requests for organ donation as well as family decision makers approached
      by OPO staff about organ donation. Telephone interviews (N = 1,087) with family
      decision makers assessed the attitudes, perceptions, and behaviors regarding the
      request for organ donation of families of designated donors as compared with
      those of patients who did not formally designate themselves as donors. RESULTS:
      Almost two thirds (65.7%) of the families of registered donors were aware of the
      decedent's decision to register as a posthumous donor. Family decision makers who
      authorized donation and those of designated donors exhibited greater knowledge of
      organ donation and more positive attitudes than decision makers who refused to
      donate. Families of designated donors had more favorable perceptions of the
      request for organ donation and were more satisfied with both the time spent
      discussing donation and the request process; fewer donor designation families
      were surprised at the request for donation. CONCLUSION: The enactment of First
      Person Authorization legislation increases the likelihood of familial
      authorization and satisfaction with the final donation outcome. As compared with
      other families approached about the option of organ donation, families of
      designated donors report having a more positive experience with the organ
      donation request process overall and greater comfort and satisfaction with the
      donation decision. LEVEL OF EVIDENCE: Epidemiologic study, level II.

PMID- 23147187
TI  - Process improvement in trauma: traumatic bladder injuries and compliance with
      recommended imaging evaluation.
AB  - BACKGROUND: We hypothesized that our compliance was low with recommended imaging
      for evaluation of traumatic bladder injury, which includes either a computed
      tomographic (CT) cystogram or plain cystogram. We sought to determine if poor
      compliance impacted diagnosis, management, and outcome of patients with bladder
      injury. METHODS: Patients with bladder injury were identified from all Level 1
      hospital trauma registries in Utah from 1996 to 2010. Details including
      presentation, management, and outcome of bladder injury were described using
      descriptive statistics and bivariate and logistic regression analysis. RESULTS: A
      total of 124 patients were identified from the trauma registries with bladder
      injury and adequate records for review. The mean age was 35 years. Blunt trauma
      occurred in 110 patients (88%). Mean Injury Severity Score was 26.3. The leading
      concomitant injury was pelvic fracture in 98 patients (79%). Bladder injury was
      extraperitoneal in 75 patients (60%), intraperitoneal in 39 (31%), and both or
      undetermined in 10 (8%). A higher risk of death was seen in intraperitoneal with
      or without concomitant extraperitoneal injury compared with extraperitoneal
      injury only (odds ratio, 12.4; 95% confidence interval, 2.37-99.2). Management
      was operative in 68 (55%) patients (95% intraperitoneal, 31% extraperitoneal). Of
      the 124 injuries, 100 were detected with imaging: standard CT scan in 70 (56%)
      and cystogram or CT cystogram in 30 (24%). The remaining injuries were discovered
      operatively or were undocumented (n = 24, 19%). Initial imaging missed or
      incorrectly diagnosed bladder injury in 13 (13%) patients (nine from standard CT
      scan and four from CT or plain cystogram). In five cases diagnosed by standard CT
      scan, extraperitoneal injuries were misdiagnosed as intraperitoneal and
      operatively explored. CONCLUSION: There was poor compliance with imaging
      recommendations for evaluation of suspected bladder injury by either CT cystogram
      or plain cystogram at Level 1 trauma centers in Utah. We have implemented a
      genitourinary trauma imaging algorithm designed to minimize errors in bladder
      injury diagnosis. LEVEL OF EVIDENCE: Therapeutic study, level IV.

PMID- 23147188
TI  - A functional role for transverse (t-) tubules in the atria.
AB  - Mammalian ventricular myocytes are characterised by the presence of an extensive
      transverse (t-) tubule network which is responsible for the synchronous rise of
      intracellular Ca(2+) concentration ([Ca(2+)]i) during systole. Disruption to the
      ventricular t-tubule network occurs in various cardiac pathologies and leads to
      heterogeneous changes of [Ca(2+)]i which are thought to contribute to the reduced
      contractility and increased susceptibility to arrhythmias of the diseased
      ventricle. Here we review evidence that, despite the long-held dogma of atrial
      cells having no or very few t-tubules, there is indeed an extensive and
      functionally significant t-tubule network present in atrial myocytes of large
      mammals including human. Moreover, the atrial t-tubule network is highly plastic
      in nature and undergoes far more extensive remodelling in heart disease than is
      the case in the ventricle with profound consequences for the resulting systolic
      Ca(2+) transient. In addition to considering the functional role of the t-tubule
      network in the healthy and diseased atria we also provide an overview of recent
      data concerning the putative factors controlling the formation of t-tubules and
      conclude by posing some important questions that currently remain to be addressed
      and whether or not targeting t-tubules offers potential novel therapeutic
      possibilities for heart disease.

PMID- 23147189
TI  - Explaining the failures of obesity therapy: willpower attenuation, target
      miscalculation or metabolic compensation?

PMID- 23147190
TI  - What precision-protein-tuning and nano-resolved single molecule sciences can do
      for each other.
AB  - While innovations in modern microscopy, spectroscopy, and nanoscopy techniques
      have made single molecule observation a standard in many laboratories, the actual
      design of meaningful fluorescence reporter systems now hinders major scientific
      breakthroughs. Even though the field of chemical biology is supercharging the
      fluorescence toolbox, surprisingly few strategies exist that make the transition
      from model systems to biologically relevant applications. At the same time, the
      number of microscopy techniques is growing dramatically. We explain our view on
      how the impact of modern technologies is influenced not only by further hard- and
      software developments, but also by the availability and suitability of protein
      engineering tools. We identify how the largely independent research fields of
      chemical biology and fluorescence nanoscopy can influence each other to
      synergistically drive future technology that can visualize the localization,
      structure, and dynamics of molecular function without constraints.

PMID- 23147191
TI  - Pemetrexed for previously treated patients with non-small cell lung cancer and
      differences in efficacy according to thymidylate synthase expression.
AB  - The purpose of this study was to evaluate the efficacy of pemetrexed monotherapy
      in previously treated patients with advanced non-small cell lung cancer (NSCLC)
      including salvage treatment, and to evaluate whether thymidylate synthase (TS)
      expression is a predictor for pemetrexed efficacy. Hundred and four previously
      treated patients with advanced NSCLC who received pemetrexed monotherapy were
      retrospectively evaluated for clinical efficacy and toxicity. If available,
      tissue specimens of patients were also analyzed immunohistochemically for TS
      expression. The patients' median age was 65 years (range: 43-82). An overall
      response rate of 9.6% and a median progression-free survival (PFS) time of 3.4
      months were achieved. The response rates for the second-line, third-line, fourth
      line or further treatments were 9.1, 9.3 and 10.2% (p = 0.33); the median PFS
      were 3.3, 3.2 and 3.8 months (p = 0.21). The median follow-up duration was 14.9
      months; the median overall survival (OS) was 11.9 months. The median PFS and OS
      were significantly longer in the TS-negative group than in the TS-positive group
      (5.8 months vs. 1.6 months; p = 0.03, and 14.7 months vs. 8.6 months; p = 0.04,
      respectively). Pemetrexed monotherapy could be considered as an option in the
      fourth or later lines of treatment of previously treated patients with advanced
      NSCLC as well as a second- or third-line treatment, and TS expression may be a
      potentially predictive factor for pemetrexed efficacy in NSCLC patients.

PMID- 23147192
TI  - The changing face of hepatitis C in the new era of direct-acting antivirals.
AB  - The approval of the first protease inhibitors as treatment for hepatitis C virus
      (HCV) infection is rapidly transforming the way patients with chronic hepatitis C
      are managed. Treatment regimens are moving to combinations given for shortened
      periods, excluding poorly tolerated subcutaneous interferon, and providing rates
      of cure exceeding 75%. The recognition of HCV infection as a systemic disease,
      not limited to producing liver damage, in which extrahepatic complications play a
      major role as the cause of morbidity and mortality, is prompting the treatment of
      a growing number of HCV-infected individuals. However, new challenges are
      emerging, including the need to diagnose a substantial proportion of asymptomatic
      carriers, the risk of potentially harmful drug-drug interactions and the high
      cost of medications. The future will probably see a progressive marginalization
      of residual HCV populations, with increasing over-representation of illegal
      immigrants, alcohol abusers, intravenous drug users and the mentally disabled.

PMID- 23147193
TI  - Rings, chains and helices: new antimicrobial silver coordination compounds with
      (iso-)nicotinic acid derivatives.
AB  - Complexes with silver ions have great potential for applications in medicine.
      Appropriate bidentate ligands, binding to silver ions, are able to generate
      coordination polymers as well as molecular entities as a function of ligand
      flexibility, conformation and length. Here we present the continuation of our
      previous studies in this field with ligands based on oligomers of polyethylene
      glycol, functionalized at both ends with either nicotinic or isonicotinic acid.
      The structures of three ligands and nine new coordination compounds are
      presented. A large variety of structures are obtained as a function of
      counterion, solvent and ligand-to-metal ratio, such as isolated rings, offset
      stacked rings, parallel chains and entangled chains, and their antimicrobial
      properties as well as biocompatibility are assessed.

PMID- 23147194
TI  - A porous metal-organic framework based on Zn6O2 clusters: chemical stability, gas
      adsorption properties and solvatochromic behavior.
AB  - A highly connected 3D metal-organic framework with tfz-d topology based on
      Zn(6)O(2) clusters and flexible carboxylate ligands has been synthesized. The
      obtained Zn-MOF shows solvatochromic behavior for fluorescence sensing of small
      molecules, gas adsorption properties and exceptional chemical stability and might
      have applications for separation and detection purposes.

PMID- 23147195
TI  - Video-assisted thoracoscopic left lower lobectomy in a patient with lung cancer
      and a right aortic arch.
AB  - A right aortic arch is a rare congenital anomaly, with a reported incidence of
      around 0.1%. A patient with a right aortic arch underwent video-assisted thoracic
      surgery left lower lobectomy and mediastinal lymph node dissection for squamous
      cell carcinoma. There was no aortic arch or descending aorta in the left thoracic
      cavity, but the esophagus. There was no anomaly in the location or branching of
      the pulmonary vessels, the bronchi, and the lobulation of the lungs. The vagus
      nerve was found at the level of the left pulmonary artery. The arterial ligament
      was found between the left subclavian artery and the left pulmonary artery. The
      recurrent laryngeal nerve was recurrent around the left subclavian artery. A
      Kommerell diverticulum was found at the origin of the left subclavian artery. The
      patient experienced no complications. We conclude that video-assisted
      thoracoscopic lobectomy with mediastinal dissection is feasible for treating lung
      cancer with a right aortic arch.

PMID- 23147196
TI  - Adrenal oncocytic neoplasm: a systematic review.
AB  - INTRODUCTION: Oncocytic neoplasms as tumors arising in the adrenal glands are
      rare, usually considered as nonfunctional and benign. In the current literature,
      there are extremely limited reports of adrenal oncocytic neoplasms; as to date,
      only 147 cases have been described. The rarity of the event prompted this study
      which reviews and presents the incidence, histology, diagnosis and therapy of
      adrenal oncocytic neoplasms. MATERIALS AND METHODS: A review by systematic
      literature search was done using the MEDLINE(r)/Cochrane libraries from 1950 to
      date using the medical subject headings 'oncocytoma', 'adrenal gland', 'adrenal
      oncocytoma', 'adrenal oncocytic neoplasm' and 'adrenal oncocytic carcinoma'.
      RESULTS: Adrenal oncocytic neoplasm is a rare disease, usually incidentally
      detected because only 17% are functional adrenal masses. The typical oncocyte
      displays abundant granular eosinophilic cytoplasm, due to the accumulation of
      mitochondria. Computed tomography and magnetic resonance imaging are not able to
      identify or differentiate benign and malignant oncocytic neoplasms. The mainstay
      of therapy is adrenalectomy, recently performed by laparoscopy. The prognosis is
      good for benign tumors, while adrenocortical oncocytic carcinoma has a poor
      survival rate of only 5 years. CONCLUSIONS: Adrenal oncocytic neoplasm, a rare
      and mostly benign tumor, usually presents as an incidental, large adrenal mass;
      surgery is the mainstay of therapy, by means of laparoscopy which is now the most
      diffuse approach to adrenalectomy.

PMID- 23147197
TI  - Drugging the undruggable: transcription therapy for cancer.
AB  - Transcriptional regulation is often the convergence point of oncogenic signaling.
      It is not surprising, therefore, that aberrant gene expression is a hallmark of
      cancer. Transformed cells often develop a dependency on such a reprogramming
      highlighting the therapeutic potential of rectifying cancer-associated
      transcriptional abnormalities in malignant cells. Although transcription is
      traditionally considered as undruggable, agents have been developed that target
      various levels of transcriptional regulation including DNA binding by
      transcription factors, protein-protein interactions, and epigenetic alterations.
      Some of these agents have been approved for clinical use or entered clinical
      trials. While artificial transcription factors have been developed that can
      theoretically modulate expression of any given gene, the emergence of reliable
      reporter assays greatly facilitates the search for transcription-targeted agents.
      This review provides a comprehensive overview of these developments, and
      discusses various strategies applicable for developing transcription-targeted
      therapeutic agents.

PMID- 23147199
TI  - ADMA, SDMA and L-arginine/ADMA ratio but not DDAH genetic polymorphisms are
      reliable predictors of diabetic nephropathy progression as identified by
      competing risk analysis.
AB  - BACKGROUND/AIMS: Complex interplay of genetic and (patho)physiological factors
      influence availability of nitric oxide during the development and progression of
      diabetic complications. We assessed predictive value of commonly studied
      methylated asymmetric and symmetric dimethylarginines (ADMA and SDMA) and
      selected single nucleotide polymorphisms (SNPs) in dimethylarginine
      dimethylaminohydrolase (DDAH) 1 and 2 genes for the progression of diabetic
      nephropathy (DN). METHODS: A total of 341 type 1 and type 2 diabetes patients
      with variable degree of kidney disease were included at baseline. Plasma levels
      of ADMA, SDMA and L-arginine were measured and six tagging SNPs in DDAH1 and 2
      were determined. Progression of DN was defined as a transition from any given
      stage to a more advanced stage of albuminuria. Competing risk analysis was
      applied. RESULTS: Plasma levels of ADMA and SDMA significantly correlated with
      GFR. No significant genotype-phenotype relationship was ascertained for ADMA and
      DDAH variants, but SNP rs805304 exhibited marginally significant association with
      DN. ADMA, SDMA and L-arginine/ADMA ratio standardised to GFR were identified as
      significant predictors of DN progression but not GFR decline using multivariate
      competing risk analysis. CONCLUSIONS: In our study we confirmed potentially
      significant role of ADMA and SDMA for the assessment of risk of DN progression in
      European diabetic population.

PMID- 23147200
TI  - Antibiotic doxorubicin and its derivative bind milk beta-lactoglobulin.
AB  - beta-Lactoglobulin (beta-LG) is a member of lipocalin superfamily of transporters
      for small hydrophobic molecules such as doxorubicin and its derivatives. We
      located the binding sites of doxorubicin (DOX) and N-(trifluoroacetyl)
      doxorubicin (FDOX) with beta-lactoglobulin in aqueous solution at physiological
      conditions, using FTIR, CD and fluorescence spectroscopic methods as well as
      molecular modeling. Structural analysis showed that DOX and FDOX bind beta-LG via
      both hydrophilic and hydrophobic contacts with overall binding constants of K(DOX
      )(beta)(-LG)=1.0 (+/- 0.4)* 10(4)M(-1) and K(FDOX-)(beta)(-LG)=2.5 (+/- 0.5)*
      10(4)M(-1) and the number of drug molecules bound per protein (n) 1.2 for DOX and
      0.6 for FDOX. Molecular modeling showed the participation of several amino acids
      in the drug-protein complexes with the free binding energy of -8.12 kcal/mol for
      DOX-beta-LG and -7.74 kcal/mol for FDOX-beta-LG complexes. DOX and FDOX do not
      share similar binding sites with beta-LG. Protein conformation showed minor
      alterations with reduction of beta-sheet from 58% (free protein) to 57-51% in the
      drug-beta-LG complexes. beta-LG can transport doxorubicin and its derivative in
      vitro.

PMID- 23147202
TI  - Interview with Maurizio Prato.

PMID- 23147201
TI  - Molecular aspects on the specific interaction of homoisoflavonoids to DNA.
AB  - Homoisoflavonoids (3-benzylidenechroman-4-ones) are related to flavonoids and
      occur as natural products and exhibit biological activity. These compounds have
      been reported to possess antioxidant, antifungal, hypocholesterolemic,
      antimutagenic and antiviral activities. This study was designed to examine the
      interactions of four synthetic homoisoflavonoids (BMC, BPC, HBC and HBMC) with
      calf-thymus DNA in aqueous solution at physiological conditions, using constant
      DNA concentration (6.25 mM) and various homoisoflavonoids/polynucleotide
      (phosphate) ratios of 1/120, 1/80, 1/40, 1/20, 1/10 and 1/5. Fourier transform
      infrared (FTIR) and UV-Visible spectroscopic methods were used to determine the
      ligand binding modes, the binding constants and the stability of
      homoisoflavonoids-DNA complexes in aqueous solution. Spectroscopic evidence
      showed major binding of homoisoflavonoids to DNA with overall binding constants
      of K(BMC-DNA)=9.37(+/- 0.34)* 10(3)M(-1), K(BPC-DNA)=1.8(+/- 0.09)* 10(4)M(-1),
      K(HBC-DNA)=1.3(+/- 0.19)* 10(3)M(-1) and K(HBMC-DNA)=4.7(+/- 0.41)* 10(3)M(-1).
      The affinity of homoisoflavonoids-DNA binding is in the order of
      BPC>BMC>HBMC>HBC. No biopolymer secondary structural changes were observed upon
      homoisoflavonoids interaction and DNA remains in the B-family structure in these
      complexes.

PMID- 23147198
TI  - Study human pancreatic cancer in mice: how close are they?
AB  - Pancreatic cancer is the fourth leading cause of cancer deaths and is
      characterized by dismal prognosis. Xenograft and genetically engineered mouse
      (GEM) models have recapitulated critical elements of human pancreatic cancer,
      providing useful tools to probe the underlying cause of cancer etiology. In this
      review, we provide a brief description of the common genetic lesions that occur
      during the development of pancreatic cancer. Next, we describe the strengths and
      weaknesses of these two models and highlight key discoveries each has made.
      Although the relative merits of GEM and xenograft pancreatic cancer mouse models
      are subject to debate, both systems have and will continue to yield essential
      insights in understanding pancreatic cancer etiology. This information is
      critical for the development of new methods to screen, treat, and prevent
      pancreatic cancer.

PMID- 23147203
TI  - Bypass surgery with psychological and spiritual support (the BY.PASS Study):
      results of a pragmatic trial based on patients' preference.
AB  - BACKGROUND: Some general hospitals within the German health system provide
      supportive interventions, psychological as well as spiritual, to their patients.
      It remains to be proven if these interventions are effective when used in routine
      clinical practice. AIM: To evaluate the effectiveness of psychological and
      spiritual interventions on improving recovery following bypass surgery. METHODS:
      The BY.PASS study is a pragmatic, patient preference trial (ISRCTN 07297983).
      Adult patients scheduled for elective coronary bypass surgery were enrolled.
      Patients were assigned to study conditions according to their personal
      preference: preference for psychological interventions, for spiritual
      interventions or for no intervention. Patients who were open for any kind of
      intervention were randomly assigned either to psychological or spiritual
      interventions. During a control period, patients were asked about their
      preference, but did not receive any interventions. Primary outcomes of the study
      were in-hospital morbidity and early mortality. Psychological measures served as
      secondary outcomes. RESULTS: A total of 847 patients were enrolled. Patients of
      the control (n = 260) and the intervention group (n = 269) who explicitly wanted
      to have interventions were compared. No significant treatment effects either for
      morbidity (d = 0.08, 95% CI -0.09 to 0.25), or for mortality (OR = 1.81; 95% CI
      0.50-6.57) could be found. A reduction of negative mood resulted from both
      interventions. CONCLUSIONS: Although the effects observed were small, the study
      can serve as a basis to discuss methodological as well as theoretical aspects of
      a pragmatic trial, based upon patients' preferences.

PMID- 23147204
TI  - Expression, purification and biochemical characterization of Methanocaldococcus
      jannaschii DNA ligase.
AB  - We describe the biochemical characterization of Methanocaldococcus jannaschii (M.
      jannaschii) DNA ligase and its potential application in single nucleotide
      polymorphism (SNP) genotyping. The recombinant M. jannaschii DNA ligase is an ATP
      dependent ligase. The ligase activity was dependent on metal ions of Mg(2+) and
      Mn(2+). The optimal concentrations of ATP cofactor and Mg(2+) ion were 0.01-2 and
      10 mM, respectively. The optimal pH value for DNA ligation was 8.5. High
      concentrations of NaCl inhibited DNA ligation. The effects of mismatches on
      joining short oligonucleotides by M. jannaschii DNA ligase were fully
      characterized. The mismatches at the first position 5' to the nick inhibited
      ligation more than those at the first position 3' to the nick. The mismatches at
      other positions 5' to the nick (3rd to 7th sites) exhibited less inhibition on
      ligation. However, the introduction of a C/C mismatch at the third position 5' to
      the nick could completely inhibit the ligation of the terminal-mismatched nick of
      an oligonucleotide duplex by M. jannaschii DNA ligase. Therefore, introducing an
      additional mismatch at the third position 5' to the SNP site is a more effective
      approach in genotyping by M. jannaschii DNA ligase.

PMID- 23147205
TI  - High yield purification of JNK1beta1 and activation by in vitro reconstitution of
      the MEKK1->MKK4->JNK MAPK phosphorylation cascade.
AB  - The c-Jun N-terminal kinase (JNK) pathway forms part of the mitogen-activated
      protein kinase (MAPK) signaling pathways comprising a sequential three-tiered
      kinase cascade. Here, an upstream MAP3K (MEKK1) phosphorylates and activates a
      MAP2K (MKK4 and MKK7), which in turn phosphorylates and activates the MAPK, JNK.
      The C-terminal kinase domain of MEKK1 (MEKK-C) is constitutively active, while
      MKK4/7 and JNK are both activated by dual phosphorylation of S/Y, and T/Y
      residues within their activation loops, respectively. While improvements in the
      purification of large quantities of active JNKs have recently been made,
      inadequacies in their yield, purity, and the efficiency of their phosphorylation
      still exist. We describe a novel and robust method that further improves upon the
      purification of large yields of highly pure, phosphorylated JNK1beta1, which is
      most suitable for biochemical and biophysical characterization. Codon
      harmonization of the JNK1beta1 gene was used as a precautionary measure toward
      increasing the soluble overexpression of the kinase. While JNK1beta1 and its
      substrate ATF2 were both purified to >99% purity as GST fusion proteins using GSH
      agarose affinity chromatography and each cleaved from GST using thrombin,
      constitutively-active MEKK-C and inactive MKK4 were separately expressed in E.
      coli as thioredoxin-His(6)-tagged proteins and purified using urea refolding and
      Ni(2+)-IMAC, respectively. Activation of JNK1beta1 was then achieved by
      successfully reconstituting the JNK MAPK activation cascade in vitro; MEKK-C was
      used to activate MKK4, which in turn was used to efficiently phosphorylate and
      activate large quantities of JNK1beta1. Activated JNK1beta1 was thereafter able
      to phosphorylate ATF2 with high catalytic efficiency.

PMID- 23147206
TI  - Purification and separation of the 20S immunoproteasome from the constitutive
      proteasome and identification of the subunits by LC-MS.
AB  - The proteasome is a multicatalytic protease complex present in all eukaryotic
      cells, which plays a critical role in regulating essential cellular processes.
      During the immune response to pathogens, stimulation by gamma interferon induces
      the production of a special form of proteasome, the immunoproteasome.
      Inappropriate increase of proteosomal activity has been linked to inflammatory
      and autoimmune diseases. Selective inhibition of the immunoproteasome specific
      LMP7 subunit was shown to block inflammatory cytokine secretion in human PBMC,
      thus making the immunoproteasome an interesting target to fight autoimmune
      diseases. This paper describes a method for purification and separation of the
      20S immunoproteasomes from the constitutive proteasome, which is ubiquitously
      present in all cells, based on hydrophobic interaction chromatography. The
      purified immunoproteasome showed several bands, between 20-30 kDa, when subjected
      to polyacrylamide gel electrophoresis under denaturing conditions. The purified
      proteasome complexes had a molecular mass of approximately 700 kDa as estimated
      by gel filtration. Identification of the catalytic subunits in the
      immunoproteasomes was performed in Western blot with antibodies directed
      specifically against either the constitutive or the immunoproteasome subunits.
      The purified immunoproteasome possessed all three protease activities associated
      with the proteasome complex. LC/MS analysis confirmed the presence of the three
      immunoproteasome catalytic subunits in the purified immunoproteasome.

PMID- 23147207
TI  - Multimodality imaging of intrauterine devices with an emphasis on the emerging
      role of 3-dimensional ultrasound.
AB  - The intrauterine contraceptive device (IUD) is one of the most widely used
      reversible contraception methods throughout the world. With advancing technology,
      it has rapidly gained acceptance through its increased effectiveness and
      practicality compared with more invasive means such as laparoscopic tubal
      ligation. This pictorial essay will present the IUDs most commonly used today. It
      will illustrate both normal and abnormal positions of IUDs across all cross
      sectional imaging modalities including 2-dimensional ultrasound, computed
      tomography, and magnetic resonance imaging, with a focus on the emerging role of
      3-dimensional ultrasound as the modality of choice.

PMID- 23147208
TI  - Triiodothyronine (T3) induces proinsulin gene expression by activating PI3K:
      possible roles for GSK-3beta and the transcriptional factor PDX-1.
AB  - Thyroid hormone (TH) activates PI3K and Akt, leading to glucose uptake in rat
      skeletal muscle cells and proliferation of insulinoma cells, respectively.
      However, TH actions on pancreatic beta cells have been little explored, which
      lead us to evaluate the TH eff ects on proinsulin gene expression, and the
      involvement of PI3K/Akt/GSK-3beta signaling pathway, and a transcriptional factor
      for insulin (PDX-1). INS-1E cells were sorted into 3 groups: control and TH
      depleted treated or not with T3 for 30 min. Cells were also previously treated
      with actinomycin D (ActD), cycloheximide (CHX), wortmannin or Akt inhibitor.
      Proinsulin mRNA expression was evaluated by real time PCR, and pGSK-3beta and PDX
      1 protein content was analyzed by Western blotting. TH depletion decreased
      proinsulin mRNA content, which was restored after acute T3 treatment. ActD, CHX
      and wortmannin, but not Akt inhibitor, prevented the rapid stimulatory eff ect of
      T3 on proinsulin mRNA expression. TH depletion did not affect the phosphorylated
      GSK-3beta and PDX-1 protein content; but T3 treatment led to an increase in the
      content of these proteins. These data indicate that T3 acutely increases
      proinsulin mRNA expression, by mechanisms which depends on the activation of
      PI3K, but not of Akt, and may involve the inactivation of GSK-3beta by
      phosphorylation. Since GSK-3beta enhances PDX-1 degradation rate, the GSK-3beta
      inactivation could explain the increase of PDX-1 content in T3-treated cells.
      Considering that PDX-1 is one of the most important transcriptional factors for
      proinsulin gene expression, its enhancement may underlie the increased proinsulin
      mRNA content acutely induced by T3.

PMID- 23147209
TI  - Efficacy of rimonabant in obese patients with binge eating disorder.
AB  - In obesity, a dysregulation of the endocannabinoid system has been shown. The
      endocannabinoid receptor blockage by rimonabant demonstrated interesting
      metabolic effects. However, the role of rimonabant in weight loss of patients
      with binge eating disorder has not been investigated. Thus, our aim was to
      evaluate the effects of rimonabant on body weight in obese patients with binge
      eating disorders. This multicenter, randomized, double-blind, placebo-controlled
      study included 289 obese subjects (age 18-70 years, body mass index 30-45
      kg/m(2)) with binge eating disorders. Subjects were randomized (1:1) to receive
      rimonabant 20 mg/day or placebo for 6 months. In total, 289 participants (age:
      43.2+/-10.5 yrs, 91% of women) were randomized. The completer rate was similar
      (71%) in both treatment and placebo groups. Participants treated with rimonabant
      lost 4.7+/-5.2% of their initial body weight, vs. 0.4+/-4.5% in the placebo group
      (difference between both groups: 4.4+/-0.6 kg, p<0.0001). The rimonabant group
      showed a greater reduction on the binge eating scale total score (mean+/-SD  -
      40.9+/-35.2%) vs. placebo ( - 29.9+/-34.6%, p=0.02). The incidence of treatment
      emergent adverse events was comparable in both the rimonabant (82.5%) and placebo
      (76.0%) group. Discontinuations due to treatment emergent adverse events occurred
      in 13.3% rimonabant-treated vs. 6.2% placebo-treated participants. In conclusion,
      this is the only randomised, placebo-controlled, double-blind trial having
      assessed the effect of rimonabant in patients with binge eating disorders. The
      rimonabant treatment reduced body weight significantly more than placebo in obese
      subjects with binge eating. Trial registration number (clinicaltrials.gov):
      NCT00481975.

PMID- 23147210
TI  - Effectiveness of metformin on weight loss in non-diabetic individuals with
      obesity.
AB  - OBJECTIVE: The efficacy of metformin for the treatment of obesity has been
      evaluated in few clinical trials with inconclusive results. Moreover, the
      effectiveness in a real-life outpatient setting has not been tested until today.
      In this study we aimed to examine the effectiveness of metformin as a weight
      reducing drug in obese and overweight patients with regard to their degree of
      insulin resistance. DESIGN AND PATIENTS: We treated 154 consecutive patients with
      a body mass index >=27 kg/m(2) in an outpatient setting over 6 months with
      metformin up to a dosage of 2,500 mg per day. Additionally, we included 45
      untreated patients as controls. Patients were monitored for weight changes over 6
      months. Before metformin treatment was started insulin sensitivity was determined
      in all patients by calculating HOMA index and Matsuda index after a 75 g oral
      glucose tolerance test. RESULTS: The mean weight loss in the metformin treated
      group was 5.8+/-7.0 kg (5.6+/-6.5%). Untreated controls gained 0.8+/-3.5 kg
      (0.8+/-3.7%) on average. Patients with severe insulin resistance lost
      significantly more weight as compared to insulin sensitive patients. The
      percentage of weight loss was independent of age, sex or BMI. CONCLUSION:
      Metformin is an effective drug to reduce weight in a naturalistic outpatient
      setting in insulin sensitive and insulin resistant overweight and obese patients.

PMID- 23147211
TI  - Ropivacaine infusion in diabetics subject with peripheral arterial disease. A
      prospective study.
AB  - BACKGROUND: Peripheral arterial disease (PAD) predicts cardiovascular and
      cerebrovascular ischemic events. PAD treatment is aimed at reducing clinical
      symptoms, local tissue loss and at preventing complications. AIMS: To evaluated
      the effect of peridural analgesia on peripheral perfusion and pain control.
      METHODS: In 280 diabetic subjects with severe limb ischemia (65.7% males and
      34.3% females, mean age 59.3+/-14.4 years) with a failure of medical treatment
      and contraindications to endovascular and/or surgical reperfusion, we performed a
      30-day long peridural ropivacaine infusion, monitoring blood pressure, VAS and
      ABI periodically. RESULTS: During ropivacaine infusion VAS significantly
      decreased (from 4.06+/-0.343 to 1.96+/-0.413, p<0.001). Furthermore, in the 261
      (93.2%) subjects achieving a VAS value <=2 during infusion, the effect was
      maintained after infusion withdrawing. ABI significantly improved both during
      infusion (from 0.30+/-0.04 at baseline to 0.65+/-0.05 at T30, p<0.001) and after
      infusion withdrawing as compared with baseline values. CONCLUSIONS: 30-day
      peridural analgesia with ropivacaine is a valuable therapeutic option in severe
      peripheral limb ischemia subjects with contraindication to surgery and with
      pharmacological therapy failure.

PMID- 23147212
TI  - Influence of mechanical forces as a part of nail configuration.
AB  - BACKGROUND: Clinicians encounter pincer nails at a high incidence among bedridden
      cases who are free from weight bearing. The mechanical force transmitted by
      walking and loading may affect the nail configuration. This study was aimed at
      evaluating the influence of mechanical forces on the nail configuration. METHODS:
      Study 1 was conducted on a sample size of 318 great toenails, with the subjects
      classified into the following 3 groups: healthy volunteers, participants who were
      bedridden for less than 3 months, and participants who were bedridden for more
      than 3 months. Study 2 was conducted in 12 subjects with unilateral loading.
      ASSESSMENTS: The configuration of the great toenails, in terms of the curve index
      (defined as the nail height/nail width), was compared. RESULTS: In study 1, the
      curve index increased significantly as the duration of the bedridden state became
      longer (17.5 +/- 4.75, 28.9 +/- 11.0, 36.4 +/- 9.58, respectively). In study 2,
      the curve index on the nonloaded side was significantly higher than that on the
      loaded side (40.0 +/- 8.63 vs. 27.0 +/- 8.39). CONCLUSION: Our results suggest
      that mechanical forces may affect the nail configuration and be involved in the
      pathophysiology of nail deformities.

PMID- 23147213
TI  - A survey of invasive catheter practices in U.S. burn centers.
AB  - Burn-specific guidelines for optimal catheter rotation, catheter type, insertion
      methods, and catheter site care do not exist, and practices vary widely from one
      burn unit to another. The purpose of this study was to define current practices
      and identify areas of practice variation for future clinical investigation. An
      online survey was sent to the directors of 123 U.S. burn centers. The survey
      consisted of 23 questions related to specific practices in placement and
      maintenance of central venous catheters (CVCs), arterial catheters, and
      peripherally inserted central catheters (PICCs). The overall response rate was
      36%; response rate from verified centers was 52%. Geographic representation was
      wide. CVC and arterial catheter replacement varied from every 3 days (24% of
      sites) to only for overt infection (24% of sites); 23% of sites did not use the
      femoral position for CVC placement. Nearly 60% of units used some kind of
      antiseptic catheter. Physicians inserted the majority of catheters, and 22% of
      sites used nonphysicians for at least some insertions. Ultrasound was routinely
      used by less than 50% of units. A wide variety of post-insertion dressing
      protocols were followed. PICCs were used in some critically injured patients in
      37% of units; the majority of these users did not rotate PICCs. Thus, it can be
      surmised that wide practice variation exists among burn centers with regard to
      insertion and maintenance of invasive catheters. Areas with particular
      variability that would be appropriate targets of clinical investigation are line
      rotation protocols, catheter site care protocols, and use of PICCs in acute
      burns.

PMID- 23147214
TI  - A comparison of dexmedetomidine and midazolam for sedation in severe pediatric
      burn injury.
AB  - Dexmedetomidine (DEX) is an alpha-adrenergic agonist that has been used for
      sedation during invasive procedures and endotracheal intubation. In pediatric
      burn injury, DEX has been shown to be safe as a long-term sedative in the
      intensive care unit (ICU). However, comparison of DEX with traditional sedatives,
      such as midazolam, for sedation in pediatric burn injury has not been performed.
      The purpose of this study was to compare DEX with midazolam in terms of sedation,
      efficacy, and side effects in children with burn injury. A retrospective review
      of all children with a TBSA burn injury >=20% admitted from December 2008 to
      September 2010 was performed. Children who received a continuous DEX infusion
      were compared with children receiving a continuous midazolam infusion. Data
      collected included: age, TBSA burn, ventilator days, ICU days, hypotensive
      episodes, bradycardic episodes, and Richmond Agitation Score (RAS). A total of 21
      patients who received DEX infusions were compared with 21 age-matched and burn
      size-matched patients who received midazolam infusions. Of the 21 DEX patients,
      nine also received midazolam infusions, eight prior to DEX and one after. These
      patients did not receive DEX and midazolam simultaneously. There was no
      difference in age (6.9 vs 6.4 years), TBSA (45.5 vs 49.2%), ICU days (45.3 vs
      55.4), and ventilator days (38.5 vs 45.5) between the DEX and midazolam patients,
      respectively. The mean duration of infusion was 22.5 +/- 24.9 days for DEX and
      20.1 +/- 24.8 days for midazolam. DEX patients had a mean RAS of -0.91 +/- 0.8.
      Midazolam patients were more sedated with a mean RAS of -1.33 +/- 0.7. Only one
      episode of bradycardia was noted in the DEX group. The DEX group had fewer
      hypotensive episodes (mean arterial pressure <60 mm Hg) while on infusion
      compared with the midazolam group (15.8 vs 29.7 episodes). Thus, it can be
      surmised that DEX is a safe and effective sedative for pediatric burn patients.
      Compared to midazolam, DEX may provide more effective sedation and less sedation
      related hypotension.

PMID- 23147215
TI  - Treatment of iatrogenic fungal infections: a black mold defines a new gray zone
      in medicine.

PMID- 23147216
TI  - Design principles of a universal protein degradation machine.
AB  - The 26S proteasome is a 2.5-MDa, 32-subunit ATP-dependent protease that is
      responsible for the degradation of ubiquitinated protein targets in all
      eukaryotic cells. This proteolytic machine consists of a barrel-shaped peptidase
      capped by a large regulatory particle, which contains a heterohexameric AAA+
      unfoldase as well as several structural modules of previously unknown function.
      Recent electron microscopy (EM) studies have allowed major breakthroughs in
      understanding the architecture of the regulatory particle, revealing that the
      additional modules provide a structural framework to position critical, ubiquitin
      interacting subunits and thus allow the 26S proteasome to function as a universal
      degradation machine for a wide variety of protein substrates. The EM studies have
      also uncovered surprising asymmetries in the spatial arrangement of proteasome
      subunits, yet the functional significance of these architectural features remains
      unclear. This review will summarize the recent findings on 26S proteasome
      structure and discuss the mechanistic implications for substrate binding,
      deubiquitination, unfolding, and degradation.

PMID- 23147217
TI  - An insertion in the catalytic trigger loop gates the secondary channel of RNA
      polymerase.
AB  - Escherichia coli DksA and GreB bind to RNA polymerase (RNAP), reaching inside the
      secondary channel, with similar affinities but have different cellular functions.
      DksA destabilizes promoter complexes whereas GreB facilitates RNA cleavage in
      arrested elongation complexes (ECs). Although the less abundant GreB may not
      interfere with DksA regulation during initiation, reports that DksA acts during
      elongation and termination suggest that it may exclude GreB from arrested
      complexes, potentially triggering genome instability. Here, we show that GreB
      does not compete with DksA during termination whereas DksA, even when present in
      several hundredfold molar excess, does not inhibit GreB-mediated cleavage of the
      nascent RNA. Our findings that DksA does not bind to backtracked or active ECs
      provide an explanation for the lack of DksA activity on most ECs that we reported
      previously, raising a question of what makes a transcription complex susceptible
      to DksA. Structural modeling suggests that i6, an insertion in the catalytic
      trigger loop, hinders DksA access into the channel, restricting DksA action to a
      subset of transcription complexes. In support of this hypothesis, we demonstrate
      that deletion of i6 permits DksA binding to ECs and that the distribution of DksA
      and i6 in bacterial genomes is strongly concordant. We hypothesize that DksA
      binds to transcription complexes in which i6 becomes mobile, for example, as a
      consequence of weakened RNAP interactions with the downstream duplex DNA.

PMID- 23147218
TI  - A phase I trial and in vitro studies combining ABT-751 with carboplatin in
      previously treated non-small cell lung cancer patients.
AB  - BACKGROUND: ABT-751 is a novel antimitotic agent that exerted cytotoxic effects
      in preclinical studies. Carboplatin has efficacy in treating advanced non-small
      cell lung cancer (NSCLC) in combination with other drugs. METHODS: Lung cancer
      cell lines were treated with ABT-751 and/or carboplatin to investigate their
      impact on cell growth. A phase I study with an expansion cohort was conducted in
      previously treated NSCLC patients. The primary objective was the maximum
      tolerated dose (MTD); secondary objectives were objective response rates, median
      survival, time to tumor progression, dose-limiting toxicities (DLTs), and
      pharmacodynamic evaluation of buccal swabs. RESULTS: Combining ABT-751 with
      carboplatin significantly reduced growth and induced apoptosis of lung cancer
      cell lines. Twenty advanced NSCLC patients were enrolled. MTD was ABT-751 125 mg
      orally twice daily for 7 days with carboplatin AUC 6. DLTs included fatigue,
      ileus, neutropenia and pneumonitis. Two patients had confirmed partial responses.
      Median overall survival was 11.7 months (95% CI 5.9-27.0). Time to tumor
      progression was 2.8 months (95% CI 2.0-2.7). Four of 6 patients showed decreased
      cyclin D1 protein in posttreatment versus pretreatment buccal swabs. CONCLUSION:
      Combining ABT-751 with carboplatin suppressed growth of lung cancer cell lines
      and had modest clinical antitumor activity in advanced NSCLC previously treated
      predominantly with carboplatin. Further studies of this combination are not
      recommended while investigations of biomarkers in different patient populations,
      alternative schedules and combinations may be pursued.

PMID- 23147220
TI  - Nanogold-based bio-bar codes for label-free immunosensing of proteins coupling
      with an in situ DNA-based hybridization chain reaction.
AB  - A label-free, non-enzyme immunosensing strategy is designed for ultrasensitive
      electronic detection of disease-related proteins (carcinoembryonic antigen as a
      model) by using gold nanoparticle-based bio-bar codes and an in situ amplified
      DNA-based hybridization chain reaction.

PMID- 23147219
TI  - A multi-omic systems approach to elucidating Yersinia virulence mechanisms.
AB  - The underlying mechanisms that lead to dramatic differences between closely
      related pathogens are not always readily apparent. For example, the genomes of
      Yersinia pestis (YP) the causative agent of plague with a high mortality rate and
      Yersinia pseudotuberculosis (YPT) an enteric pathogen with a modest mortality
      rate are highly similar with some species specific differences; however the
      molecular causes of their distinct clinical outcomes remain poorly understood. In
      this study, a temporal multi-omic analysis of YP and YPT at physiologically
      relevant temperatures was performed to gain insights into how an acute and highly
      lethal bacterial pathogen, YP, differs from its less virulent progenitor, YPT.
      This analysis revealed higher gene and protein expression levels of conserved
      major virulence factors in YP relative to YPT, including the Yop virulon and the
      pH6 antigen. This suggests that adaptation in the regulatory architecture, in
      addition to the presence of unique genetic material, may contribute to the
      increased pathogenecity of YP relative to YPT. Additionally, global transcriptome
      and proteome responses of YP and YPT revealed conserved post-transcriptional
      control of metabolism and the translational machinery including the modulation of
      glutamate levels in Yersiniae. Finally, the omics data was coupled with a
      computational network analysis, allowing an efficient prediction of novel
      Yersinia virulence factors based on gene and protein expression patterns.

PMID- 23147221
TI  - Inhibition of a basal transcription factor 3-like gene Osj10gBTF3 in rice results
      in significant plant miniaturization and typical pollen abortion.
AB  - BTF3, which was originally recognized as a basal transcription factor, has been
      known to be involved in transcription initiation, translational regulation and
      protein localization in many eukaryotic organisms. However, its function remains
      largely unknown in plant species. In the present study, we analyzed a BTF3
      related sequence in Oryza sativa L. subsp. japonica, which shares the conserved
      domain of a nascent polypeptide-associated complex with human BTF3, and was
      referred to as Osj10gBTF3. The expression of Osj10gBTF3 was primarily
      constitutive and generally modulated by salt, high temperature and exogenous
      phytohormone stress. The Osj10gBTF3::EGFP (enhanced green fluorescence protein)
      fusion protein was localized in both the nucleus and cytoplasmic membrane system.
      Inhibition of Osj10gBTF3 led to significant morphological changes in all detected
      tissues and organs, with a reduced size of between 25% and 52%. Furthermore, the
      pollen that developed was completely sterile, which was correlated with the
      altered expression of two Rf (fertility restorer)-like genes that encode
      pentatricopeptide repeat-containing proteins OsPPR676 and OsPPR920, translational
      initiation factors OseIF3e and OseIF3h, and the heat shock protein OsHSP82. These
      findings were verified through a yeast two-hybrid assay using a Nipponbare callus
      cDNA library as bait followed by the reverse transcription-PCR analysis of total
      leaf or anther RNAs. Our demonstration of the important role of Osj10gBTF3 in
      rice growth and development provides new insights showing that more complex
      regulatory functions are associated with BTF3 in plants.

PMID- 23147222
TI  - Arabidopsis ABCB21 is a facultative auxin importer/exporter regulated by
      cytoplasmic auxin concentration.
AB  - The phytohormone auxin is critical for plant growth and many developmental
      processes. Members of the P-glycoprotein (PGP/ABCB) subfamily of ATP-binding
      cassette (ABC) transporters have been shown to function in the polar movement of
      auxin by transporting auxin over the plasma membrane in both monocots and dicots.
      Here, we characterize a new Arabidopsis member of the ABCB subfamily,
      ABCB21/PGP21, a close homolog of ABCB4, for which conflicting transport
      directionalities have been reported. ABCB21 is strongly expressed in the abaxial
      side of cotyledons and in junctions of lateral organs in the aerial part, whereas
      in roots it is specifically expressed in pericycle cells. Membrane fractionation
      by sucrose density gradient centrifugation followed by Western blot showed that
      ABCB21 is a plasma membrane-localized ABC transporter. A transport assay with
      Arabidopsis protoplasts suggested that ABCB21 was involved in IAA transport in an
      outward direction, while naphthalene acetic acid (NAA) was a less preferable
      substrate for ABCB21. Further functional analysis of ABCB21 using yeast import
      and export assays showed that ABCB21 mediates the 1-N-naphthylphthalamic acid
      (NPA)-sensitive translocation of auxin in an inward direction when the
      cytoplasmic IAA concentration is low, whereas this transporter mediates outward
      transport under high internal IAA. An increase in the cytoplasmic IAA
      concentration by pre-loading of IAA into yeast cells abolished the IAA uptake
      activity by ABCB21 as well as ABCB4. These findings suggest that ABCB21 functions
      as a facultative importer/exporter controlling auxin concentrations in plant
      cells.

PMID- 23147223
TI  - Delayed preconditioning prevents ischemia/reperfusion-induced endothelial injury
      in rats: role of ROS and eNOS.
AB  - Ischemic preconditioning (IPC) strongly protects against ischemia/reperfusion
      (I/R) injury; however, the molecular mechanism involved in delayed
      preconditioning-induced endothelial protection in peripheral arteries is unknown.
      Therefore, we examined using functional, morphologic and molecular biologic
      studies whether delayed IPC decreases formation of reactive oxygen species and
      upregulates endothelial nitric oxide synthase (eNOS) that in turn contributes to
      vascular endothelial protection. Adult male Sprague-Dawley rats were subjected to
      30-min ischemia induced by mesenteric artery occlusion followed by 60-min
      reperfusion 24 h after sham surgery or preconditioning (three cycles of 5-min
      ischemia/5-min reperfusion). Delayed preconditioning prevented the I/R-induced
      impairment of endothelium-dependent relaxations to acetylcholine (maximal
      relaxation: sham 91.4+/-2.2%; I/R 54.0+/-4.0%; IPC 80.2+/-6.3%). This protective
      effect was abolished by NOS inhibitor N(G)-nitro-L-arginine methyl ester and not
      changed by ascorbic acid. Electron microscopy showed marked endothelial damage
      after I/R and the ultrastructural changes were prevented by delayed
      preconditioning. Following I/R, the impairment of eNOS phosphorylation and
      expression was observed in mesenteric vessels. Furthermore, phosphatidylinositol
      3-kinase (PI3K) and Akt phosphorylation were reduced, although total PI3K and Akt
      remained unchanged. IPC restored I/R-induced impairment of eNOS expression and
      activity. This was possibly the result of the recovery of PI3K/Akt
      phosphorylation. Furthermore, I/R increased serum level of malondialdehyde,
      intravascular superoxide and nitrotyrosine generation, which were abrogated by
      IPC. These results suggest that delayed preconditioning prevented I/R-induced
      endothelial injury in peripheral resistance vasculature, both in terms of
      functional and structural changes. Endothelial protection afforded by delayed IPC
      is associated with inhibition of oxidative stress and upregulation of
      PI3K/Akt/eNOS pathway.

PMID- 23147224
TI  - ERK pathway and sheddases play an essential role in ethanol-induced CX3CL1
      release in pancreatic stellate cells.
AB  - The clinical course of chronic pancreatitis (CP) worsens with drinking, and
      pancreatic stellate cells (PSCs) have an important role in the pathogenesis of
      alcoholic CP. Chemokines recruit inflammatory cells, resulting in chronic
      pancreatic inflammation. Although serum levels of fractalkine (CX3CL1) are
      significantly elevated in patients with alcoholic CP, the mechanism of this
      elevation remains unclear. This study aims to determine the effects of cytokines,
      pathogen-associated molecular patterns (PAMPs), and ethanol and its metabolites
      on CX3CL1 secretion by PSCs. Male Wistar/Bonn Kobori (WBN/Kob) rats aged 15 to 20
      weeks were used as rodent models of CP in vivo. PSCs were isolated from 6-week
      old male Wistar rats. The effects of cytokines, PAMPs, and ethanol and its
      metabolites on chemokine production and activation of signaling pathways in PSCs
      in vitro were examined by real-time reverse transcription-polymerase chain
      reaction (RT-PCR), western blotting, and enzyme-linked immunosorbent assay.
      Expression of CX3CL1 and matrix metalloprotease (MMP)-2 was increased in the
      pancreas of WBN/Kob rats. The rat PSCs expressed CX3CL1, MMP-2, and a disintegrin
      and metalloprotease domain (ADAM) 17. Cytokines and PAMPs induced CX3CL1 release
      and activated extracellular signal-regulated kinase (ERK), MMP-9, and ADAM17.
      CX3CL1 release was suppressed by specific inhibitors of ERK, MMP, and ADAM, and
      ERK was associated with CX3CL1 transcription. Ethanol and phorbol myristate
      acetate synergistically increased CX3CL1 release. Real-time PCR and western
      blotting confirmed the synergistic activation of ERK and ADAM17. Ethanol
      synergistically increased CX3CL1 release via ERK and ADAM17 activation in PSCs.
      In conclusion, we demonstrated for the first time that ethanol synergistically
      increased CX3CL1 release from PSCs at least in part through activation of ERK
      mitogen-activated protein kinase and ADAM17. This might be one of the mechanisms
      of serum CX3CL1 elevation and disease progression in patients with alcoholic CP.

PMID- 23147225
TI  - Overexpression of TNF-alpha-converting enzyme in fibroblasts augments dermal
      fibrosis after inflammation.
AB  - TNF-alpha-converting enzyme (TACE) can cleave transmembrane proteins, such as TNF
      alpha, TNF receptors, and epidermal growth factor receptor (EGFR) ligands, to
      release the extracellular domains from the cell surface. Recent studies have
      suggested that overexpression of TACE may be associated with the pathogenesis of
      inflammation and fibrosis. To determine the roles of TACE in inflammation and
      fibrosis, TACE transgenic (TACE-Tg) mice, which overexpressed TACE systemically,
      were generated. As the transgene-derived TACE was expressed as an inactive form,
      no spontaneous phenotype developed in TACE-Tg mice. However, the transgene
      derived TACE could be converted to an active form by furin in vitro and by
      phorbol myristate acetate (PMA) in vivo. Subcutaneous injection of PMA into mice
      induced inflammatory cell infiltration 1 day later and subsequent dermal fibrosis
      7 days later. Interestingly, the degree of dermal fibrosis at day 7 was
      significantly higher in TACE-Tg mice than in wild-type mice. Correspondingly, PMA
      increased the expression of type I collagen in the primary culture of dermal
      fibroblasts derived from TACE-Tg mice. Furthermore, phosphorylated EGFR was
      increased in the fibroblasts by the PMA treatment. The collective findings
      suggest that TACE overexpression and activation in fibroblasts could shed off
      putative EGFR ligands. Subsequently, the soluble EGFR ligands could bind and
      activate EGFR on fibroblasts, and then increase the type I collagen expression
      resulting in induction of dermal fibrosis. These results also suggest that TACE
      and EGFR on fibroblasts may be novel therapeutic targets of dermal fibrosis,
      which is induced after diverse inflammatory disorders of the skin.

PMID- 23147226
TI  - Morphological and microarray analyses of human hepatocytes from xenogeneic host
      livers.
AB  - We previously produced mice with human hepatocyte (h-hep) chimeric livers by
      transplanting h-heps into albumin enhancer/promoter-driven urokinase-type
      plasminogen activator-transgenic severe combined immunodeficient (SCID) mice with
      liver disease. The chimeric livers were constructed with h-heps, mouse
      hepatocytes, and mouse hepatic sinusoidal cells (m-HSCs). Here, we investigated
      the morphological features of the chimeric livers and the h-hep gene expression
      profiles in the xenogeneic animal body. To do so, we performed
      immunohistochemistry, morphometric analyses, and electron microscopic
      observations on chimeric mouse livers, and used microarray analyses to compare
      gene expression patterns in hepatocytes derived from chimeric mouse hepatocytes
      (c-heps) and h-heps. Morphometric analysis revealed that the ratio of hepatocytes
      to m-HSCs in the chimeric mouse livers were twofold higher than those in the SCID
      mouse livers, corresponding to twin-cell plates in the chimeric mouse liver. The
      h-heps in the chimeric mouse did not show hypoxia even in the twin-cell plate
      structure, probably because of low oxygen consumption by the h-heps relative to
      the mouse hepatocytes (m-heps). Immunohistochemical and electron microscopic
      examinations revealed that the sinusoids in the chimeric mouse livers were
      normally constructed with h-heps and m-HSCs. However, a number of microvilli
      projected into the intercellular clefts on the lateral aspects of the
      hepatocytes, features typical of a growth phase. Microarray profiles indicated
      that ~82% of 16 605 probes were within a twofold range difference between h-heps
      and c-heps. Cluster and principal component analyses showed that the gene
      expression patterns of c-heps were extremely similar to those of h-heps. In
      conclusion, the chimeric mouse livers were normally reconstructed with h-heps and
      m-HSCs, and expressed most human genes at levels similar to those in human
      livers, although the chimeric livers showed morphological characteristics typical
      of growth.

PMID- 23147227
TI  - Transitive inference in jackdaws (Corvus monedula).
AB  - Transitive inference (TI) refers to the cognitive ability to derive relationships
      between items that have never been presented together before. TI could be a
      useful tool for individuals living in large social groups, as these are
      confronted with an increasing number of possible dyadic relationships between
      group members. Through TI, one could potentially identify rank relationships
      between group members and thereby avoid costly direct agonistic interactions.
      Jackdaws seem ideal candidates to test for the ability of TI as they live in
      relatively complex groups, in which such skills could be useful. We presently
      report the results of jackdaws in a touch screen experiment. Three individuals
      were trained to memorise an ordered sequence of five differently coloured squares
      (A-E), which were presented in four pairs consisting of two adjacent colours each
      (A/B, B/C, C/D, D/E). After reaching the pre-defined criteria in each single
      colour pair in a time comparable to other species, they were confronted with an
      unknown pair of two non-adjacent colours (B/D). The birds were able to identify
      the relationship according to the previously learned sequence by preferring B
      over D.

PMID- 23147229
TI  - A novel statistical measure for sequence comparison on the basis of k-word
      counts.
AB  - Numerous efficient methods based on word counts for sequence analysis have been
      proposed to characterize DNA sequences to help in comparison, retrieval from the
      databases and reconstructing evolutionary relations. However, most of them seem
      unrelated to any intrinsic characteristics of DNA. In this paper, we proposed a
      novel statistical measure for sequence comparison on the basis of k-word counts.
      This new measure removed the influence of sequences' lengths and uncovered bulk
      property of DNA sequences. The proposed measure was tested by similarity search
      and phylogenetic analysis. The experimental assessment demonstrated that our
      similarity measure was efficient.

PMID- 23147228
TI  - Clinical features and predictors for disease natural progression in adults with
      Pompe disease: a nationwide prospective observational study.
AB  - BACKGROUND: Due partly to physicians' unawareness, many adults with Pompe disease
      are diagnosed with great delay. Besides, it is not well known which factors
      influence the rate of disease progression, and thus disease outcome. We
      delineated the specific clinical features of Pompe disease in adults, and mapped
      out the distribution and severity of muscle weakness, and the sequence of
      involvement of the individual muscle groups. Furthermore, we defined the natural
      disease course and identified prognostic factors for disease progression.
      METHODS: We conducted a single-center, prospective, observational study. Muscle
      strength (manual muscle testing, and hand-held dynamometry), muscle function
      (quick motor function test), and pulmonary function (forced vital capacity in
      sitting and supine positions) were assessed every 3-6 months and analyzed using
      repeated-measures ANOVA. RESULTS: Between October 2004 and August 2009, 94
      patients aged between 25 and 75 years were included in the study. Although
      skeletal muscle weakness was typically distributed in a limb-girdle pattern, many
      patients had unfamiliar features such as ptosis (23%), bulbar weakness (28%), and
      scapular winging (33%). During follow-up (average 1.6 years, range 0.5-4.2
      years), skeletal muscle strength deteriorated significantly (mean declines of 
      1.3% point/year for manual muscle testing and of -2.6% points/year for hand-held
      dynamometry; both p<0.001). Longer disease duration (>15 years) and pulmonary
      involvement (forced vital capacity in sitting position <80%) at study entry
      predicted faster decline. On average, forced vital capacity in supine position
      deteriorated by 1.3% points per year (p=0.02). Decline in pulmonary function was
      consistent across subgroups. Ten percent of patients declined unexpectedly fast.
      CONCLUSIONS: Recognizing patterns of common and less familiar characteristics in
      adults with Pompe disease facilitates timely diagnosis. Longer disease duration
      and reduced pulmonary function stand out as predictors of rapid disease
      progression, and aid in deciding whether to initiate enzyme replacement therapy,
      or when.

PMID- 23147230
TI  - A semi-stochastic cell-based model for in vitro infected 'wound' healing through
      motility reduction: a simulation study.
AB  - We consider the migration and viability of individual cells in bacterial-infected
      cell colonies. Cell movement is assumed to take place as a result of sensing the
      strain energy density as a mechanical stimulus. The model is based on tracking
      the motion and viability of each individual cell in a cell colony, and the
      formalism was published in an earlier paper. The present innovations are an
      application to a simulation of a 'wound healing assay' in which bacteria infect
      the wound through impairing the motility of cells and an extension with effects
      from inertia. Though based on simple principles, the model is based on
      experiments on living fibroblasts on a flat substrate.

PMID- 23147231
TI  - Inter-species competition-facilitation in stochastic riparian vegetation
      dynamics.
AB  - Riparian vegetation is a highly dynamic community that lives on river banks and
      which depends to a great extent on the fluvial hydrology. The stochasticity of
      the discharge and erosion/deposition processes in fact play a key role in
      determining the distribution of vegetation along a riparian transect. These
      abiotic processes interact with biotic competition/facilitation mechanisms, such
      as plant competition for light, water, and nutrients. In this work, we focus on
      the dynamics of plants characterized by three components: (1) stochastic forcing
      due to river discharges, (2) competition for resources, and (3) inter-species
      facilitation due to the interplay between vegetation and fluid dynamics
      processes. A minimalist stochastic bio-hydrological model is proposed for the
      dynamics of the biomass of two vegetation species: one species is assumed
      dominant and slow-growing, the other is subdominant, but fast-growing. The
      stochastic model is solved analytically and the probability density function of
      the plant biomasses is obtained as a function of both the hydrologic and biologic
      parameters. The impact of the competition/facilitation processes on the
      distribution of vegetation species along the riparian transect is investigated
      and remarkable effects are observed. Finally, a good qualitative agreement is
      found between the model results and field data.

PMID- 23147232
TI  - Statistical models for jointly analyzing multiple allometries.
AB  - As the reciprocal of simple allometry equation, power allometry equation can also
      be used to define allometry scaling but the scaling exponent has an opposite
      meaning to that of simple allometry equation. Based on this observation, a joint
      static allometry scaling model of entire body size on multiple partial body size
      is established, which can not only simultaneously evaluate allometry scaling of
      multiple partial body sizes, but also take into account the correlations among
      multiple partial body sizes, facilitating subsequent statistical inference and
      practice. Since ontogenetic allometry may be time-dependent, ontogenetic
      allometry is estimated by jointly analyzing changes of entire and multiple
      partial body sizes as growth time using multivariate stepwise analysis. Joint
      analysis of allometry scaling is suitable for multiple biological traits and
      functions with same property or comparability, which is illustrated by two
      examples.

PMID- 23147233
TI  - Fission-fusion bat behavior as a strategy for balancing the conflicting needs of
      maximizing information accuracy and minimizing infection risk.
AB  - Fission-fusion behavior, which is widely reported in social animals, has been
      considered as a mechanism for adapting to changing environmental conditions.
      Although several hypotheses have been proposed to explain the potential benefits
      of fission-fusion behavior, there are only a few theoretical studies that have
      systematically explored its mechanism or quantitatively examined the potential
      forces shaping its evolution. We developed a social learning model to investigate
      the mechanism and evolutionary forces that underlie a fission-fusion society. In
      particular, we focused on the day-roost choices of bat individuals because bat
      societies represent one of the most sophisticated fission-fusion systems. The
      assumptions of the study were as follows. Each individual selects a single day
      roost to use, and forms a roosting group with roost mates. Bats randomly choose a
      roost to visit in order to inspect its quality. Inspection is not always
      accurate, i.e., it includes some error. After inspection, bats return to the
      current day-roost and share the new information with roost mates. Each bat
      estimates the quality of each potential roost by social learning and chooses
      which one to use based on the relative value of expected roost quality. The size
      distribution of sub-colonies is determined by this choice behavior. Three roost
      switching behaviors (settlement, synchronized movement, and fission-fusion
      grouping) were predicted depending on two factors (the level of difficulty of
      evaluating roost quality and the capacity to remember roost quality information).
      Settlement behavior, in which most bats remain in the best roost, led to the
      highest fitness because the accuracy of estimating roost quality was improved
      when bats exchanged information with members in a large group. However, when
      disease transmission was combined with learning dynamics, the cost of infection
      significantly increased under both settlement and synchronized movement
      behaviors, and eventually fission-fusion behavior led to the highest fitness.
      These results highlight two conflicting factors: learning in a large group
      improves information accuracy, but living in a small group effectively reduces
      the risk of spreading disease. Dynamic change of group size by fission-fusion can
      resolve the dilemma between these two conflicting factors.

PMID- 23147234
TI  - Modeling the influence of nucleus elasticity on cell invasion in fiber networks
      and microchannels.
AB  - Cell migration in highly constrained extracellular matrices is exploited in
      scaffold-based tissue engineering and is fundamental in a wide variety of
      physiological and pathological phenomena, among others in cancer invasion and
      development. Research into the critical processes involved in cell migration has
      mainly focused on cell adhesion and proteolytic degradation of the external
      environment. However, rising evidence has recently shown that a number of cell
      derived biophysical and mechanical parameters, among others nucleus stiffness and
      cell deformability, plays a major role in cell motility, especially in the
      ameboid-like migration mode in 3D confined tissue structures. We here present an
      extended cellular Potts model (CPM) first used to simulate a micro-fabricated
      migration chip, which tests the active invasive behavior of cancer cells into
      narrow channels. As distinct features of our approach, cells are modeled as
      compartmentalized discrete objects, differentiated in the nucleus and in the
      cytosolic region, while the migration chamber is composed of channels of
      different widths. We find that cell motile phenotype and velocity in open spaces
      (i.e., 2D flat surfaces or large channels) are not significantly influenced by
      cell elastic properties. On the contrary, the migratory behavior of cells within
      subcellular and subnuclear structures strongly relies on the deformability of the
      cytosol and of the nuclear cluster, respectively. Further, we characterize two
      migration dynamics: a stepwise way, characterized by fluctuations in cell length,
      within channels smaller than nucleus dimensions and a smooth sliding (i.e.,
      maintaining constant cell length) behavior within channels larger than the
      nuclear cluster. These resulting observations are then extended looking at cell
      migration in an artificial fiber network, which mimics cell invasion in a 3D
      extracellular matrix. In particular, in this case, we analyze the effect of
      variations in elasticity of the nucleus on cell movement. In order to summarize,
      with our simulated migration assays, we demonstrate that the dimensionality of
      the environment strongly affects the migration phenotype and we suggest that the
      cytoskeletal and nuclear elastic characteristics correlate with the tumor cell's
      invasive potential.

PMID- 23147235
TI  - Netrin-1 attenuates the progression of renal dysfunction by inhibiting
      peritubular capillary loss and hypoxia in 5/6 nephrectomized rats.
AB  - BACKGROUND/AIMS: The aim of this study was to investigate the effect of netrin-1
      on peritubular capillary (PTC) loss and hypoxia in 5/6 nephrectomized (Nx) rats.
      METHODS: Male Sprague-Dawley rats were divided into three groups (n = 10
      rats/group): sham-operated rats treated with control adenovirus; 5/6 Nx rats
      treated with control adenovirus; and 5/6 Nx rats treated with recombinant
      adenovirus mediated netrin-1 gene (Ad-netrin-1) therapy. Rats were killed 12
      weeks after surgery. Blood urea nitrogen (BUN), serum creatinine (Scr) and 24-h
      urinary albumin excretion rates were measured. Pathological changes in renal
      tissues were analyzed histologically. The concentration of netrin-1, CD34, and
      hypoxia-inducible factor-1alpha (HIF-1alpha) were analyzed by
      immunohistochemistry, Western blotting and real-time PCR. RESULTS: Renal function
      and histopathological damage were significantly improved in Adnetrin-1 treated
      5/6 Nx rats, compared with rats treated with the control adenovirus in the 5/6 Nx
      group. Furthermore, Ad-netrin-1 treatment induced a significant increase in renal
      PTC density, accompanied by a significant decrease in HIF-1alpha expression.
      CONCLUSION: Adenovirus mediated netrin-1 treatment attenuates PTC damage,
      relieves tissues hypoxia and improves renal function, thus alleviating renal
      pathological changes and interstitial fibrosis in 5/6 Nx rats.

PMID- 23147236
TI  - Phonological processing is uniquely associated with neuro-metabolic
      concentration.
AB  - Reading is a complex process involving recruitment and coordination of a
      distributed network of brain regions. The present study sought to establish a
      methodologically sound evidentiary base relating specific reading and
      phonological skills to neuro-metabolic concentration. Single voxel proton
      magnetic resonance spectroscopy was performed to measure metabolite concentration
      in a left hemisphere region around the angular gyrus for 31 young adults with a
      range of reading and phonological abilities. Correlation data demonstrated a
      significant negative association between phonological decoding and normalized
      choline concentration and as well as a trend toward a significant negative
      association between sight word reading and normalized choline concentration,
      indicating that lower scores on these measures are associated with higher
      concentrations of choline. Regression analyses indicated that choline
      concentration accounted for a unique proportion of variance in the phonological
      decoding measure after accounting for age, cognitive ability and sight word
      reading skill. This pattern of results suggests some specificity for the negative
      relationship between choline concentration and phonological decoding. To our
      knowledge, this is the first study to provide evidence that choline concentration
      in the angular region may be related to phonological skills independently of
      other reading skills, general cognitive ability, and age. These results may have
      important implications for the study and treatment of reading disability, a
      disorder which has been related to deficits in phonological decoding and
      abnormalities in the angular gyrus.

PMID- 23147237
TI  - Comparison of diffusion-weighted fMRI and BOLD fMRI responses in a verbal working
      memory task.
AB  - Diffusion-weighted functional MRI (DfMRI) has been reported to have a different
      response pattern in the visual cortex than that of BOLD-fMRI. Especially, the
      DfMRI signal shows a constantly faster response at both onset and offset of the
      stimulus, suggesting that the DfMRI signal might be more directly linked to
      neuronal events than the hemodynamic response. However, because the DfMRI
      response also contains a residual sensitivity to BOLD this hypothesis has been
      challenged. Using a verbal working memory task we show that the DfMRI time-course
      features are preserved outside visual cortices, but also less liable to between
      subject/between-regional variation than the BOLD response. The overall findings
      not only support the feasibility of DfMRI as an approach for functional brain
      imaging, but also strengthen the uniqueness of the DfMRI signal origin.

PMID- 23147238
TI  - Lymphangioma of pyeloureteral junction: an extremely rare case.
AB  - Benign tumors of the proximal ureter are very rare. Many of them could be
      confused with urothelial carcinoma and unnecessarily treated by nephrectomy. In
      this case, we present the treatment of a lymphangioma localized in the upper
      ureter, which is an example of benign tumor. During treatment percutaneous tumor
      resection, an organ-sparing approach, was employed.

PMID- 23147239
TI  - The association between physical morbidity and subtypes of severe depression.
AB  - BACKGROUND: Physical illness and depression are related, but the association
      between specific physical diseases and diagnostic subtypes of depression remains
      poorly understood. This study aimed to clarify the relationship between a number
      of physical diseases and the nonpsychotic and psychotic subtype of severe
      depression. METHODS: This is a historical prospective cohort study. The study
      population consisted of all patients diagnosed with ICD-10 severe depression,
      either nonpsychotic or psychotic subtype, in Danish psychiatric hospitals between
      1994 and 2008. The patients' history of physical disease was assessed using the
      Danish National Patient Register. Using logistic regression it was investigated
      whether specific physical diseases were associated with relative increased risk
      for subsequent development of either the nonpsychotic or psychotic depressive
      subtype. RESULTS: A total of 24,173 patients with severe depression were included
      in the study. Of those, 8,260 (34%) were of the psychotic subtype. A history of
      the following physical diseases, as opposed to their absence, increased the
      relative risk for subsequent development of the nonpsychotic compared to the
      psychotic depressive subtype [adjusted incidence odds ratio (AIOR) nonpsychotic
      vs. psychotic]: ischemic heart disease (AIOR = 1.3, p < 0.001), hypertension
      (AIOR = 1.2, p = 0.008), stroke (AIOR = 1.2, p = 0.042) and chronic lower
      pulmonary disease (AIOR = 1.2, p = 0.005). The total load of physical disease
      also increased the relative risk of nonpsychotic depression [AIOR = 1.05 (per
      disease), p = 0.001]. CONCLUSIONS: This study revealed that, in severe
      depression, a history of physical disease increased the relative risk of the
      nonpsychotic rather than the psychotic subtype.

PMID- 23147241
TI  - Efficient supramolecular synthesis of a robust circular light-harvesting Bodipy
      dye based array.
AB  - We herein present the supramolecular construction of a completely fluorescent
      unquenched multichromophoric wheel consisting of boron dipyrromethene dyes
      arranged perpendicularly to the circular plane.

PMID- 23147242
TI  - Endocytosis and autophagy: Shared machinery for degradation.
AB  - Two key questions in the autophagy field are the mechanisms that underlie the
      signals for autophagy initiation and the source of membrane for expansion of the
      nascent membrane, the phagophore. In this review, we discuss recent findings
      highlighting the role of the classical endosomal pathway, from plasma membrane to
      lysosome, in the formation and expansion of the phagophore and subsequent
      degradation of the autophagosome contents. We also highlight the striking
      conservation of regulatory factors between the two pathways, including those
      regulating membrane budding and fusion, and the role of the lysosome in sensing
      the nutrient status of the cell, regulating mTORC1 activity, and ultimately the
      initiation of autophagy. Editor's suggested further reading in BioEssays The
      evolution of dynamin to regulate clathrin-mediated endocytosis Abstract.

PMID- 23147244
TI  - Binding of isoquinoline alkaloids berberine, palmatine and coralyne to
      hemoglobin: structural and thermodynamic characterization studies.
AB  - Berberine, palmatine and coralyne, the isoquinoline alkaloids distributed in many
      botanical families, are extensively investigated due to their potential
      therapeutic actions and clinical utilities. In this work, their binding
      characteristics to hemoglobin (Hb) were studied by UV-vis absorption
      spectroscopy, fluorescence spectroscopy, circular dichroism spectroscopy,
      isothermal calorimetric titration and differential scanning calorimetric
      techniques. The results indicated that all the three alkaloids caused strong
      fluorescence quenching of Hb by the static quenching mechanism, but with
      differing quenching efficiencies. There was a single binding site on Hb for these
      alkaloids. According to the theory of Forster resonance energy transfer, the
      binding distances between beta-Trp37 of Hb and berberine, palmatine and coralyne
      were evaluated to be 2.78 nm, 2.64 nm and 3.29 nm, respectively. The result of
      synchronous fluorescence, circular dichroism and 3D fluorescence revealed that
      the polarity around Trp residues experienced a significant increase in the
      presence of alkaloids. The binding was favoured by enthalpy and entropy changes.
      Results of circular dichroism, 3D and synchronous fluorescence studies confirmed
      that the binding of the alkaloids significantly changed the secondary structure
      of Hb. The studies revealed that berberine and palmatine bound to a site near to
      the alpha1beta2 interface on Hb different than coralyne but the affinity of
      coralyne was one order higher than that of berberine and palmatine.

PMID- 23147243
TI  - Exploring a charge-central strategy in the solution of Poisson's equation for
      biomolecular applications.
AB  - Continuum solvent treatments based on the Poisson-Boltzmann equation have been
      widely accepted for energetic analysis of biomolecular systems. In these
      approaches, the molecular solute is treated as a low dielectric region and the
      solvent is treated as a high dielectric continuum. The existence of a sharp
      dielectric jump at the solute-solvent interface poses a challenge to model the
      solvation energetics accurately with such a simple mathematical model. In this
      study, we explored and evaluated a strategy based on the "induced surface charge"
      to eliminate the dielectric jump within the finite-difference discretization
      scheme. In addition to the use of the induced surface charges in solving the
      equation, the second-order accurate immersed interface method is also
      incorporated to discretize the equation. The resultant linear system is solved
      with the GMRES algorithm to explicitly impose the flux conservation condition
      across the solvent-solute interface. The new strategy was evaluated on both
      analytical and realistic biomolecular systems. The numerical tests demonstrate
      the feasibility of utilizing induced surface charge in the finite-difference
      solution of the Poisson-Boltzmann equation. The analysis data further show that
      the strategy is consistent with theory and the classical finite-difference method
      on the tested systems. Limitations of the current implementations and further
      improvements are also analyzed and discussed to fully bring out its potential of
      achieving higher numerical accuracy.

PMID- 23147245
TI  - Racial disparity in renal cell carcinoma patient survival according to
      demographic and clinical characteristics.
AB  - BACKGROUND: Patients with renal cell carcinoma (RCC) who are black tend to have
      poorer prognosis than similar patients who are white. This study examined whether
      the racial disparity in RCC patient survival varies by demographic and clinical
      characteristics. METHODS: Nearly 40,000 patients (4359 black and 34,991 white)
      diagnosed with invasive RCC from 1992 to 2007 were identified from 12 registries
      in the National Cancer Institute Surveillance, Epidemiology, and End Results
      program, covering approximately 14% of the US population. Relative survival rates
      through 2008 were computed using the actuarial method. RESULTS: Proportionally
      more blacks than whites were diagnosed with RCC under age 50 and with localized
      cancer. Overall, the 5-year relative survival rates were 72.6% (95% confidence
      interval 72.0%-73.2%) for white and 68.0% (66.2%-69.8%) for black patients.
      Survival was higher among women than men and among younger than older patients.
      Survival decreased with advancing tumor stage and, within each stage, decreased
      with increasing tumor size. Patients with clear cell RCC, a more common form
      among whites, had poorer prognosis than patients with papillary or chromophobe
      subtypes, which are more common among blacks. Survival for patients who received
      no surgical treatment (10.5% of white patients and 14.5% of black patients) was
      substantially lower than for patients treated with nephrectomy, with similar
      survival among whites and blacks. In all other demographic and clinical subgroups
      of patients, whites consistently had a survival advantage over blacks.
      CONCLUSIONS: Patients with RCC who are white consistently have a survival
      advantage over those RCC patients who are black, regardless of age, sex, tumor
      stage or size, histological subtype, or surgical treatment.

PMID- 23147246
TI  - A prospective analysis of free flap monitoring techniques: physical examination,
      external Doppler, implantable Doppler, and tissue oximetry.
AB  - No universally accepted method of flap monitoring exists, and several techniques
      are in use. Repeated physical examination is most popular and is often
      supplemented with a handheld, external Doppler, and/or implantable Doppler
      probes; near-infrared spectroscopy is less commonly used. We investigated the
      nursing and resident house staff's experience and confidence with physical exam
      for flap monitoring. Also, a consecutive series of 38 patients with free flaps
      were monitored using physical examination, external Doppler, implantable arterial
      and venous Doppler probes, and near-infrared spectroscopy. Five patients
      developed signs of microvascular complications within 3 days of surgery; all were
      explored and salvaged. Neither the residents nor the nursing staff were
      universally trained or experienced in flap monitoring by physical exam. In all
      patients, changes in the appearance of the flap suggestive of a microvascular
      complication lagged 30 to 60 minutes after the adjunctive monitoring methods
      indicated that a problem had occurred. Near-infrared spectroscopy was the first
      warning sign in four of the five patients. Two patients were explored before
      thrombosis of the anastomoses occurred. Near-infrared spectroscopy may identify
      early microvascular complications more reliably than physical examination,
      external Doppler, or implantable Doppler.

PMID- 23147247
TI  - A tool for enhancing strategic health planning: a modeled use of the
      International Classification of Functioning, Disability and Health.
AB  - This article describes use of the International Classification of Functioning,
      Disability and Health (ICF) as a tool for strategic planning. The ICF is the
      international classification system for factors that influence health, including
      Body Structures, Body Functions, Activities and Participation and Environmental
      Factors. An overview of strategic planning and the ICF are provided. Selected ICF
      concepts and nomenclature are used to demonstrate its utility in helping develop
      a classic planning framework, objectives, measures and actions. Some issues and
      resolutions for applying the ICF are described. Applying the ICF for strategic
      health planning is an innovative approach that fosters the inclusion of social
      ecological health determinants and broad populations. If employed from the onset
      of planning, the ICF can help public health organizations systematically
      conceptualize, organize and communicate a strategic health plan.

PMID- 23147248
TI  - A novel alpha-tropomyosin mutation associates with dilated and non-compaction
      cardiomyopathy and diminishes actin binding.
AB  - BACKGROUND: Dilated cardiomyopathy (DCM) is characterized by idiopathic
      dilatation and systolic contractile dysfunction of the ventricle(s) leading to an
      impaired systolic function. The origin of DCM is heterogeneous, but genetic
      transmission of the disease accounts for up to 50% of the cases. Mutations in
      alpha-tropomyosin (TPM1), a thin filament protein involved in structural and
      regulatory roles in muscle cells, are associated with hypertrophic cardiomyopathy
      (HCM) and very rarely with DCM. METHODS AND RESULTS: Here we present a large four
      generation family in which DCM is inherited as an autosomal dominant trait. Six
      family members have a cardiomyopathy with the age of diagnosis ranging from 5
      months to 52 years. The youngest affected was diagnosed with dilated and non
      compaction cardiomyopathy (NCCM) and died at the age of five. Three additional
      children died young of suspected heart problems. We mapped the phenotype to
      chromosome 15 and subsequently identified a missense mutation in TPM1, resulting
      in a p.D84N amino acid substitution. In addition we sequenced 23 HCM/DCM genes
      using next generation sequencing. The TPM1 p.D84N was the only mutation
      identified. The mutation co-segregates with all clinically affected family
      members and significantly weakens the binding of tropomyosin to actin by 25%.
      CONCLUSIONS: We show that a mutation in TPM1 is associated with DCM and a lethal,
      early onset form of NCCM, probably as a result of diminished actin binding caused
      by weakened charge-charge interactions. Consequently, the screening of TPM1 in
      patients and families with DCM and/or (severe, early onset forms of) NCCM is
      warranted. This article is part of a Special Issue entitled: Cardiomyocyte
      Biology: Cardiac Pathways of Differentiation, Metabolism and Contraction.

PMID- 23147250
TI  - Synthesis, molecular structure, and stability of a zirconocene derivative with
      alpha-Keggin mono-aluminum-substituted polyoxotungstate.
AB  - The synthesis and crystal structure of a zirconocene derivative with alpha-Keggin
      mono-aluminum-substituted polyoxotungstate, [alpha-PW(11)Al(OH)O(39)ZrCp(2)](2)(6
      ) (Cp = C(5)H(5)(-)) (1), which was obtained by the reaction of alpha-Keggin mono
      aluminum-substituted polyoxotungstate with a biscyclopentadienylzirconium(IV)
      complex, is described herein. Analytically pure, homogeneous, yellow crystals of
      the tetra-n-butylammonium salt of polyoxoanion 1, [(n-C(4)H(9))(4)N](6)[alpha
      PW(11)Al(OH)O(39)ZrCp(2)](2) (TBA-1), were obtained from the ca. 1 : 1 reaction
      of [(n-C(4)H(9))(4)N](4)[alpha-PW(11){Al(OH(2))}O(39)] with Cp(2)Zr(OTf)(2).THF
      (OTf = O(3)SCF(3)(-)) in acetonitrile solution under an argon atmosphere,
      followed by precipitation from water and crystallization from acetonitrile. TBA-1
      was characterized based on X-ray structure analysis, elemental analysis,
      thermogravimetric/differential thermal analysis (TG/DTA), Fourier transform
      infrared (FTIR), and solution ((31)P, (27)Al, (19)F, (1)H, and (13)C) nuclear
      magnetic resonance (NMR) spectroscopy. Single-crystal X-ray structure analysis
      revealed that the two {PW(11)AlO(40)} units are bridged by two "bent sandwich"
      Cp(2)Zr(2+) fragments with C(2) symmetry. Each zirconium center was bound to a
      terminal oxygen atom of the aluminum and tungsten sites and an edge-sharing
      oxygen atom at the Al-O-W linkage. Further, the stability towards water was
      investigated by NMR ((31)P, (1)H, and (13)C) and FTIR spectroscopy. The eta(5)
      cyclopentadienylzirconium fragments were not eliminated from the surface of
      [alpha-PW(11){Al(OH(2))}O(39)](4-) even after 24 h exposure to 50 equiv. of
      water.

PMID- 23147249
TI  - A role for sequestosome 1/p62 in mitochondrial dynamics, import and genome
      integrity.
AB  - As a signaling scaffold, p62/sequestosome (p62/SQSTM1) plays important roles in
      cell signaling and degradation of misfolded proteins. While localization of p62
      to mitochondria has been reported, a description of its function once there,
      remains unclear. Here, we report that p62 is localized to mitochondria in non
      stressed situations and demonstrate that deficiency in p62 exacerbates defects in
      mitochondrial membrane potential and energetics leading to mitochondrial
      dysfunction. We report on the relationship between mitochondrial protein import
      and p62. In a p62 null background, mitochondrial import of the mitochondrial
      transcription factor TFAM is disrupted. When p62 is returned, mitochondrial
      function is restored to more normal levels. We identify for the first time that
      p62 localization plays a role in regulating mitochondrial morphology, genome
      integrity and mitochondrial import of a key transcription factor. We present
      evidence that these responses to the presence of p62 extend beyond the protein's
      immediate influence on membrane potential.

PMID- 23147251
TI  - Inhibition of mTORC2 but not mTORC1 up-regulates E-cadherin expression and
      inhibits cell motility by blocking HIF-2alpha expression in human renal cell
      carcinoma.
AB  - PURPOSE: Molecular targeted drugs, such as mTORC1 inhibitors, have been
      clinically popularized for advanced renal cell carcinoma treatment but metastasis
      is still a serious concern. mTORC2 has several important functions, including HIF
      2alpha activation in malignant cells. HIF-2alpha suppresses E-cadherin
      expression, which is associated with tumor invasion and metastasis. We
      investigated whether mTORC2 regulates E-cadherin expression and controls cell
      motility during HIF-2alpha down-regulation in renal cell carcinoma cells.
      MATERIALS AND METHODS: We used PP242, a dual inhibitor of mTORC1/mTORC2 and the
      mTORC1 specific inhibitor rapamycin. E-cadherin expression in 786-O cells was
      examined using real-time polymerase chain reaction, Western blot and
      immunocytochemical staining. Cell motility was analyzed by time-lapse microscopy
      and wound healing assay. RESULTS: High E-cadherin expression was found in
      RCC4/VHL cells but low levels were found in VHL defective RCC4 and 786-O cells.
      HIF-2alpha expression was suppressed only in RCC4/VHL cells. In 786-O cells HIF
      2alpha inhibition induced by the dual mTORC1/C2 inhibitor PP242 (0.05 to 0.5
      MUmol/L) resulted in a dose dependent increase in E-cadherin expression and the
      restored E-cadherin was localized at cell-to-cell junctions. Treatment with the
      mTORC1 inhibitor rapamycin resulted in no significant change. The migration of
      PP242 treated cells was significantly suppressed compared with those treated with
      rapamycin. CONCLUSIONS: Results show that mTORC2 might regulate E-cadherin
      expression and suppress cell motility by controlling the mTORC2-HIF-2alpha
      signaling pathway. The dual inhibitor of mTORC1/C2 as a cadherin regulatory agent
      may be a novel therapeutic strategy with tumoricidal agents for advanced renal
      cell carcinoma.

PMID- 23147252
TI  - The screening of methicillin-resistant staphylococcus aureus in vascular surgery
      patients: a comparison of molecular testing and broth-enriched culture.
AB  - BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) is a major global
      health care-associated pathogen. This study sought to examine the prevalence of
      MRSA in patients who were admitted to a vascular surgery ward during a 3-month
      period. METHODS: MRSA screening was accomplished through the acquisition of
      nasal, throat and perineal swabs. These swabs were placed in tryptic soy broth
      that had been supplemented with 6.5% NaCl and incubated for 24 h. The resulting
      isolates were subcultured on agar plates containing 5% sheep blood. The BD
      GeneOhm MRSA assay for screening swabs was performed in accordance with the
      manufacturer's instructions. RESULTS: A total of 58 patients were included in the
      study and swabs from 232 sites were obtained during the sampling period. MRSA was
      detected in 33 samples of 12 patients during the study period; thus, there was a
      20.6% prevalence of patients who were recognized as MRSA carriers. There were
      discrepancies between the results of classical bacteriological screening and
      molecular MRSA detection methods in 8 of the patients. CONCLUSIONS: Nasal, throat
      and perineal MRSA screening can detect the carriage of this pathogen and allow
      for the timely use of appropriate infection control measures. The choice of
      screening techniques poses a challenge; it has been demonstrated that molecular
      detection methods should be performed with great sensitivity, specificity and,
      most importantly, speed. The cost of the PCR screening method is the only
      disadvantage of this approach.

PMID- 23147253
TI  - Exome sequencing in tracking clonal evolution in multiple myeloma following
      therapy.

PMID- 23147254
TI  - The ASXL-BAP1 axis: new factors in myelopoiesis, cancer and epigenetics.
AB  - The recent identification of germline and somatic mutations in BAP1 as well as in
      multiple members of the ASXL (additional sex combs-like) family of genes has
      highlighted the role of these proteins in a diverse array of biological
      functions. A diverse number of possible functions have previously been ascribed
      to ASXL1 in non-hematopoietic contexts, including physical co-operativity with
      HP1a and LSD1. Here we discuss new evidence for a BAP1-independent function of
      ASXL1 in regulating histone H3 lysine 27 methylation through interactions with
      the Polycomb-repressive complex 2 (PRC2). BAP1, a nuclear-localized
      deubiquitinase, has been shown to interact with a number of proteins, including
      ASXL1 and/or ASXL2, but the functional importance of this interaction has
      remained elusive. Here, we highlight recent work revealing the critical function
      of BAP1 in restricting myelopoiesis and in regulating hematopoietic stem cell
      function. These data provide evidence that BAP1 and ASXL1 function as a novel
      class of tumor suppressors in myeloid malignancies. BAP1 functions through
      effects on stability of host cell factor-1, and O-GlcNAcylation, and ASXL1
      impacts histone post-translational modifications through interaction with PRC2.
      Future studies investigating the mechanism of transformation by loss of BAP1 and
      ASXL1 may result in new therapeutic approaches to treat hematological
      malignancies.

PMID- 23147255
TI  - Size of bladder cancers: correlation among different types of measurement.
AB  - OBJECTIVE: It was the aim of this study to evaluate the accuracy of the
      measurement of tumor size comparing the objective size with that measured by
      preoperative cystoscopy, by preoperative ultrasound (US) and with the diameter
      described by the operator before the transurethral resection. PATIENTS AND
      METHODS: This study included 100 patients with bladder papillary endoscopic
      features of single or multiple neoplasms who were candidates for transurethral
      resection. The sizes of the same neoplasms measured during preoperative
      cystoscopy, preoperative US and described by the operator before the
      transurethral resection were evaluated. A statistical analysis of the errors of
      measurement was performed if compared with an objective measurement done with an
      ureteral catheter. RESULTS: The statistical analysis of the data shows that there
      are no substantial differences between the objective and subjective measurement,
      and therefore, the measurements reported by individual operators are reliable. On
      the contrary, the diameters given by preoperative cystoscopy and US differ
      significantly from the objective measurement. CONCLUSIONS: This study shows that
      the most reliable measurement is the subjective measurement made directly by the
      urologist in the operating room.

PMID- 23147256
TI  - Epiphora.

PMID- 23147257
TI  - The swollen optic disc.

PMID- 23147258
TI  - Management of the patient with  a ventriculoperitoneal shunt presenting with
      headache.

PMID- 23147259
TI  - How to work effectively with medical secretaries.

PMID- 23147260
TI  - Protective effect of dexpanthenol on ischemia-reperfusion-induced renal injury in
      rats.
AB  - BACKGROUND/AIMS: This experimental study was designed to investigate protective
      and therapeutic effects of Dexpanthenol (Dxp), an alcoholic analogue of
      pantothenic acid, on kidney damage induced by ischemia-reperfusion (I/R) in rats.
      METHODS: Forty rats were randomly divided into a control group and 4 I/R groups
      (1 h ischemia followed by 23 h reperfusion). Three I/R groups were treated by Dxp
      (500 mg/kg, i.p.) at 3 different time points (before ischemia, during ischemia
      and late reperfusion). The histopathological findings including apoptotic
      changes, and also tissue malondialdehyde (MDA), superoxide dismutase (SOD),
      catalase (CAT), glutathione peroxidase (GPX), blood urea nitrogen (BUN), serum
      creatinine (Cr) and albumin (Alb) levels were determined. RESULTS: Kidney tissue
      MDA levels were found to be significantly higher in the I/R group, whereas the
      values of GPX were lower when compared to the control group. The levels of SOD
      and CAT did not reach to statistical meaning level in I/R group. Dxp given during
      ischemia reduced the elevated MDA levels to the nearly control levels and this
      ameliorating effect was found as parallel to the result of GPX. Serum levels of
      BUN and Cr were significantly higher in I/R group. Dxp given during ischemia
      significantly reduced the elevated BUN and Cr levels when compared to I/R group.
      Renal I/R injury also induced extensive tubular necrosis, glomerular damage and
      apoptosis in the histological evaluation. Dxp ameliorated these histological
      damages in different amounts in all treatment groups. CONCLUSION: In this study
      the protective effects of Dxp against renal I/R injury has been evaluated for the
      first time.

PMID- 23147261
TI  - Mood and the menstrual cycle.
AB  - BACKGROUND: Premenstrual mood symptoms are considered common in women, but such
      prevailing attitudes are shaped by social expectations about gender, emotionality
      and hormonal influences. There are few prospective, community studies of women
      reporting mood data from all phases of the menstrual cycle (MC). We aimed (i) to
      analyze daily mood data over 6 months for MC phase cyclicity and (ii) to compare
      MC phase influences on a woman's daily mood with that attributable to key
      alternate explanatory variables (physical health, perceived stress and social
      support). METHOD: A random sample of Canadian women aged 18-40 years collected
      mood and health data daily over 6 months, using telemetry, producing 395 complete
      MCs for analysis. RESULTS: Only half the individual mood items showed any MC
      phase association; these links were either with the menses phase alone or the
      menses plus the premenstrual phase. With one exception, the association was not
      solely premenstrual. The menses-follicular-luteal MC division gave similar
      results. Less than 0.5% of the women's individual periodogram records for each
      mood item showed MC entrainment. Physical health, perceived stress and social
      support were much stronger predictors of mood (p < 0.0001 in each case) than MC
      phase. CONCLUSIONS: The results of this study do not support the widespread idea
      of specific premenstrual dysphoria in women. Daily physical health status,
      perceived stress and social support explain daily mood better than MC phase.

PMID- 23147262
TI  - Structure- and cell-specific effects of imidoselenocarbamates on selenoprotein
      expression and activity in liver cells in culture.
AB  - The essential micronutrient selenium (Se) exerts its biological effects mainly
      through selenoproteins thereby affecting a number of physiological pathways
      including intracellular redox control, stress response and cancer cell
      proliferation. Besides affecting selenoprotein expression, some selenocompounds
      have been synthesized and analyzed in order to serve as chemotherapeutic
      substances preferentially targeting cancer cells. This promising chemotherapeutic
      potential has recently been verified for a particular imidoselenocarbamate in a
      mouse tumor model. In the present study we tested the effects of this and a
      number of related Se-methyl- and Se-benzyl-imidoselenocarbamates on selenoprotein
      expression in nontransformed and hepatic carcinoma cells in culture. Most of the
      Se-benzyl-imidoselenocarbamates strongly stimulated selenoprotein P (SePP)
      secretion while the Se-methyl-imidoselenocarbamates elicited less pronounced
      effects in hepatocarcinoma HepG2 cells. However, most of the Se-methyl
      imidoselenocarbamates increased glutathione peroxidase (GPx) activity and
      decreased thioredoxin reductase (TXNRD) activity in parallel, while the majority
      of the Se-benzyl-imidoselenocarbamates were without a respective effect in HepG2
      cells. Performing inhibitor assays in vitro, GPx activity was unaffected by the
      imidoselenocarbamates. In contrast, most of the Se-methyl-imidoselenocarbamates
      inhibited TXNRD activity in vitro in line with the results in HepG2 cells. Both
      classes of imidoselenocarbamates strongly induced selenoprotein S (SELS)
      expression without a respective increase in ER stress or unfolded protein
      response which are known inducers of SELS biosynthesis. Notably, many of these
      effects were cancer cell-specific, and not observed in nontransformed AML12
      hepatocytes. Our results indicate that these novel selenocompounds affect
      expression and activity of crucial selenoenzymes in a compound- and cell-specific
      way in hepatocytes. Especially the Se-methyl-imidoselenocarbamates elicit a
      unique spectrum of activities by stimulating GPx activity, SELS expression and
      SePP secretion while inhibiting TXNRD activity in hepatocarcinoma cells. These
      effects represent a promising finding with respect to the identification of
      therapeutic selenocompounds, as cancer-cell specificity is combined with desired
      effects on selenoprotein expression and activity.

PMID- 23147263
TI  - The role of electron scattering in electron-induced surface chemistry.
AB  - Electron-induced chemistry on surfaces plays a key role in focused electron beam
      induced processing (FEBIP), a single-step lithography technique that has
      increasingly gained interest in the past decade. It is crucial for the
      understanding and modelling of this process to know the role of the surface in
      the electron-induced dissociation of an adsorbed precursor molecule. However, the
      electron scattering in the underlying solid makes it impossible to determine this
      directly. In this paper the contribution of electron scattering in the target on
      the measured deposition yield is calculated for the precursor MeCpPt(IV)Me(3),
      using the matrix inversion method. The calculation is based on experimental data
      for the dissociation yield and secondary electron emission. Two trends are
      observed in the analysis. Firstly, the contribution of electron scattering to the
      experimentally determined dissociation yield is not dominant for primary electron
      (PE) energies up to about 50 eV. Therefore, the role of the surface in this
      energy range can therefore reasonably be deduced from differences between
      electron-induced dissociation in the gas phase and the adsorbed phase. Secondly,
      at PE energies above 80 eV the electron scattering contributes significantly to
      the measured dissociation yield. The cross section that is calculated with the
      matrix inversion method peaks at 80-150 eV, which is typical for gas phase
      ionization. This suggests that surface interactions (other than electron
      scattering) do not dominate the chemistry for energies above PE energies of 80
      eV. The obtained result can be used as input for Monte Carlo simulations for
      focused electron beam induced deposition.

PMID- 23147264
TI  - A tailed primers protocol to identify the association of eNOS gene variable
      number of tandem repeats polymorphism with ischemic stroke in Chinese Han
      population by capillary electrophoresis.
AB  - Endothelial nitric oxide synthase (eNOS) plays an important role in mediating
      endothelium-dependent vasodilatation and antithrombotic action and is thus
      involved in the development of ischemic stroke (IS). Controversial results
      regarding the association of eNOS gene variable number of tandem repeats (VNTR)
      polymorphism with IS have been reported by conventional PCR-polyacrylamide gel
      electrophoresis methods. We aimed to identify any common association of eNOS gene
      VNTR polymorphism with IS in Chinese Han population by capillary electrophoresis
      (CE). The VNTR polymorphism of 27 bp within the eNOS intron-4 was determined by
      CE with specially designed tailed primers in Chinese Han patients with IS (n=457)
      and matched elderly controls without IS (n=457). Significant differences in BMI,
      WHR, hypertension, diabetes, smoking, TG, HDL, LDL, LDL, and FBG were observed
      between cases and controls. The distributions of eNOS VNTR polymorphism were not
      significantly associated with IS after adjustment for cardiovascular risk factors
      (OR=1.18, 95% CI: 0.82-1.69). This finding was consistent with the further meta
      analysis in Asians. The meta-analysis in Americans demonstrated that 4a/4b+4a/4a
      genotype was significantly associated with IS risk with an OR of 1.54 (95% CI,
      1.09-2.17) compared with the 4b/4b genotype. Our data suggests that BMI, WHR,
      hypertension, diabetes, smoking, TG, LDL, and FBG may increase the risk of IS.
      However, eNOS VNTR polymorphism may be not an independent major contributor for
      IS in Chinese Han population. The VNTR polymorphism might be associated with IS
      in Americans based on meta-analysis.

PMID- 23147265
TI  - An association between -866G/A polymorphism in the promoter of UCP2 and obesity:
      a meta-analysis.
AB  - -866G/A polymorphism in the promoter of UCP2 gene has been reported to be
      associated with obesity, but the results remain inconclusive. To assess the
      relation of UCP2 -866G/A polymorphism and obesity susceptibility, a meta-analysis
      was performed. PubMed, ISI, Wanfang database, VIP and CBM were searched to
      identify relevant studies up to July 31, 2012. Odds ratios (OR) and 95%
      confidence interval (95% CI) were pooled using fixed or random effect models.
      Subgroup analysis was performed by ethnicity (categorized as Asian and European).
      Heterogeneity and publication bias evaluation were performed to validate the
      credibility. Meta-regression and the 'leave one out' sensitive analysis were used
      to explore the potential sources of between-study heterogeneity. 14 studies were
      included in this meta-analysis. After exclusion of articles that deviated from
      the HWE in controls, and were the key contributors to between-study
      heterogeneity, the meta-analysis showed a significant association of the A allele
      with reduced risk of obesity in overall analysis and in European in the dominant,
      codominant and additional models. In Asian, no significant association was found
      between the -866G/A in UCP2 gene and obesity susceptibility. The meta-analysis
      suggested that UCP2 -866G/A polymorphism was associated with obesity. The A
      allele may be an important protective factor for obesity in European, but not in
      Asian. Further studies are needed to elucidate the relationship.

PMID- 23147266
TI  - Logic regression analysis of association of gene polymorphisms with low HDL:
      Tehran Lipid and Glucose Study.
AB  - INTRODUCTION: Logic regression is a generalized regression method that can
      recognize complex Boolean interactions of binary variables. It has been
      successfully applied to single-nucleotide polymorphism (SNP) data because of the
      importance of interactions in SNP association studies. The objective of this
      study is to assess the association between high-density lipoprotein (HDL)
      function and some related gene polymorphisms after adjusting for potential
      confounders using logic regression. METHODS: Subjects in this cross-sectional
      study were randomly selected from among participants of the Tehran Lipid and
      Glucose Study (TLGS). A total of 436 subjects (172 men and 264 women), aged >=20
      years, were selected to be included in the current study. Logic regression
      analysis was used in order to recognize the combination of genetic main effects
      and possible interactions associated with HDL-C level. Cross validation and
      randomization test were carried out to avoid over fitting of the models. RESULTS:
      The cross validation test suggested three Boolean combinations with four
      predictors for a fully-adjusted logic model. The fully adjusted model showed that
      those who carry an Apo E gene E3 allele or have high TG level have an odds ratio
      of 2.35 (95% CI:1.3-4.25) for having low HDL compared to other subjects. In
      addition, subjects with high TG level have an odds ratio of 2.73 (95% CI: 1.65,
      4.53) for having low HDL. CONCLUSION: The results showed that logic regression is
      a powerful method to find the interaction between high TG level and Apo E
      polymorphism associated with low HDL.

PMID- 23147267
TI  - UDP-glucuronosyltransferase 1A1 (UGT1A1) gene haplotypes and their effect on
      serum bilirubin concentration in healthy Indian adults.
AB  - The aim of the present study was to investigate the allele and genotype
      frequencies and haplotype structures of the variants in the UGT1A1 gene and their
      association with serum bilirubin levels in healthy adults. Total serum bilirubin
      levels were measured in 300 healthy adults (normal hematology and liver function
      test) and genotyping of seven SNPs was performed by PCR-RFLP, Gene Scan analysis
      and direct sequencing on the ABI Prism 310 Genetic Analyzer. Of the seven SNPs,
      four were found to be polymorphic and the frequencies of minor alleles were
      0.336, 0.431, 0.353 and 0.066 for -53(TA)7, -3279G, -3156A and 211A respectively.
      Individuals who carried the -53(TA)7, -3279G and -3156A mutant alleles in
      homozygous or heterozygous states had significantly higher mean serum bilirubin
      levels. Five major promoter haplotypes were observed: -53(TA)6/-3279T/-3156G was
      the most common haplotype, followed by -53(TA)7/-3279G/-3156A, -53(TA)6/-3279G/
      3156G, -53(TA)6/-3279G/-3156A and -53(TA)7/-3279T/-3156G with an estimated
      frequency of 0.445, 0.230, 0.083, 0.065 and 0.050 respectively. Furthermore, the
      mutant haplotype (-53(TA)7/-3279G/-3156A) was found to have a significant effect
      on bilirubin concentrations. Promoter polymorphisms and a common haplotype of the
      UGT1A1 gene are associated with serum bilirubin concentrations and could be a
      genetic risk factor for hyperbilirubinemia in Indians.

PMID- 23147268
TI  - Phylogenetic species recognition reveals host-specific lineages among poplar rust
      fungi.
AB  - Fungal species belonging to the genus Melampsora (Basidiomycota, Pucciniales)
      comprise rust pathogens that alternate between Salicaceae and other plant hosts.
      Species delineation and identification are difficult within this group due to the
      paucity of observable morphological features. Several Melampsora rusts are highly
      host-specific and this feature has been used for identification at the species
      level. However, this criterion is not always reliable since different Melampsora
      rust species can overlap on one host but specialize on a different one. To date,
      two different species recognition methods are used to recognize and define
      species within the Melampsora genus: (i) morphological species recognition, which
      is based solely on morphological criteria; and (ii) ecological species
      recognition, which combines morphological criteria with host range to recognize
      and define species. In order to clarify species recognition within the Melampsora
      genus, we applied phylogenetic species recognition to Melampsora poplar rusts by
      conducting molecular phylogenetic analyses on 15 Melampsora taxa using six
      nuclear and mitochondrial loci. By assessing the genealogical concordance between
      phylogenies, we identified 12 lineages that evolved independently, corresponding
      to distinct phylogenetic species. All 12 lineages were concordant with host
      specialization, but only three belonged to strictly defined morphological
      species. The estimation of the species tree obtained with Bayesian concordance
      analysis highlighted a potential co-evolutionary history between Melampsora
      species and their reciprocal aecial host plants. Within the Melampsora speciation
      process, aecial host may have had a strong effect on ancestral evolution, whereas
      telial host specificity seems to have evolved more recently. The morphological
      characters initially used to define species boundaries in the Melampsora genus
      are not reflective of the evolutionary and genetic relationships among poplar
      rusts. In order to construct a more meaningful taxonomy, host specificity must be
      considered an important criterion for delineating and describing species within
      the genus Melampsora as previously suggested by ecological species recognition.

PMID- 23147269
TI  - Incorporating indels as phylogenetic characters: impact for interfamilial
      relationships within Arctoidea (Mammalia: Carnivora).
AB  - Insertion and deletion events (indels) provide a suite of markers with enormous
      potential for molecular phylogenetics. Using many more indel characters than
      those in previous studies, we here for the first time address the impact of indel
      inclusion on the phylogenetic inferences of Arctoidea (Mammalia: Carnivora).
      Based on 6843 indel characters from 22 nuclear intron loci of 16 species of
      Arctoidea, our analyses demonstrate that when the indels were not taken into
      consideration, the monophyly of Ursidae and Pinnipedia tree and the monophyly of
      Pinnipedia and Musteloidea tree were both recovered, whereas inclusion of indels
      by using three different indel coding schemes give identical phylogenetic tree
      topologies supporting the monophyly of Ursidae and Pinnipedia. Our work brings
      new perspectives on the previously controversial placements among Arctoidea
      families, and provides another example demonstrating the importance of
      identifying and incorporating indels in the phylogenetic analyses of introns. In
      addition, comparison of indel incorporation methods revealed that the three indel
      coding methods are all advantageous over treating indels as missing data, given
      that incorporating indels produces consistent results across methods. This is the
      first report of the impact of different indel coding schemes on phylogenetic
      reconstruction at the family level in Carnivora, which indicates that indels
      should be taken into account in the future phylogenetic analyses.

PMID- 23147270
TI  - Color discrimination deficits in Parkinson's disease are related to cognitive
      impairment and white-matter alterations.
AB  - Color discrimination deficit is a common nonmotor manifestation of Parkinson's
      disease (PD). However, the pathophysiology of this dysfunction remains poorly
      understood. Although retinal structure changes found in PD have been suggested to
      cause color discrimination deficits, the impact of cognitive impairment and
      cortical alterations remains to be determined. We investigated the contribution
      of cognitive impairment to color discrimination deficits in PD and correlated
      them with cortical anomalies. Sixty-six PD patients without dementia and 20
      healthy controls performed the Farnsworth-Munsell 100 hue test and underwent a
      comprehensive neuropsychological assessment for mild cognitive impairment
      diagnosis. In a subgroup of 26 PD patients, we also used high-definition
      neuroanatomical magnetic resonance imaging for cortical thickness and diffusion
      tensor analysis. PD patients with mild cognitive impairment performed poorly on
      the Farnsworth-Munsell 100 hue test compared with PD patients without mild
      cognitive impairment and controls. In PD patients, performance on the Farnsworth
      Munsell 100 hue test was correlated with measures of visuospatial abilities and
      executive functions. Neuroimaging analysis revealed higher mean and radial
      diffusivity values in right posterior white-matter structures that correlated
      with poor performance on the Farnsworth-Munsell 100 hue test. No cortical
      thickness correlation reached significance. This study showed that cognitive
      impairment makes a major contribution to the color discrimination deficits
      reported in PD. Thus, performance on the Farnsworth-Munsell 100 hue test may
      reflect cognitive impairment more than color discrimination deficits in PD. Poor
      performance on the Farnsworth-Munsell 100 hue test was also associated with white
      matter alterations in right posterior brain regions.

PMID- 23147271
TI  - Two new scorpionate oxomolybdenum(VI)-poly(pyrazolyl)borate complexes: synthesis,
      structure, and catalytic performance in the oxidation of cyclohexane.
AB  - Two new oxomolybdenum(VI) complexes [(TpMoO(2))(2)(MU-O)].H(2)O (1) and (Tp(4
      I)MoO(2))(2)(MU-O) (2) were synthesized and characterized by elemental analysis,
      IR spectra, UV-Vis spectroscopy, powder X-ray diffraction, single-crystal X-ray
      diffraction and thermogravimetric analyses (TG). In addition, the catalytic
      performances of complexes 1 and 2 were studied firstly on the oxidation reaction
      of cyclohexane at room temperature.

PMID- 23147272
TI  - [Updated quality requirements regarding secondary differentiated ultrasound
      examination in prenatal diagnostics (= DEGUM level II) in the period from 18 + 0
      to 21 + 6 weeks of gestation].

PMID- 23147273
TI  - DNA surface coating of calixarene-based nanoparticles: a sequence-dependent
      binding mechanism.
AB  - An amphiphilic calix[4]arene derivative bearing four guanidino moieties at the
      upper rim and four dodecyl chains at the lower rim was shown to form stable solid
      lipid nanoparticles (SLNs) in water. The study of the interactions of these
      cationic SLNs with DNA revealed a sequence-dependent groove binding mechanism.

PMID- 23147274
TI  - Ghrelin and obestatin in human neuroendocrine tumors: expression and effect on
      obestatin levels after food intake.
AB  - BACKGROUND: Ghrelin and obestatin are derived from the same peptide hormone
      precursor and are mainly produced by the gastric mucosa. Ghrelin is involved in
      many biological processes, whereas the physiological function of obestatin needs
      further investigation. The aims of the present study were to establish the
      incidence of ghrelin- and obestatin-immunoreactive cells in a comprehensive panel
      of human neuroendocrine tumors (NETs) and to investigate if blood obestatin
      concentrations are influenced during a standardized meal stimulation test in
      healthy individuals and patients with NETs. MATERIALS AND METHODS: The expression
      of ghrelin and obestatin was investigated in NETs (n = 149) and other endocrine
      related disorders (n = 3) using immunohistochemistry with specific polyclonal
      antibodies. Coexpression of the peptides was evaluated by double
      immunofluorescence. Concentrations of obestatin in blood were measured during a
      meal test in 6 healthy individuals and 5 patients with pancreatic NETs. RESULTS:
      Ghrelin and obestatin were expressed in 14/152 and 19/152 tumor tissues,
      respectively, mainly representing NETs of foregut origin and in pancreatic tissue
      from a nesidioblastosis patient. Double immunofluorescence staining showed
      colocalization of the peptides. During the meal test, obestatin levels in blood
      were unchanged in all patients but decreased significantly in the healthy
      individuals. CONCLUSION: Only a minority of NETs express ghrelin and obestatin.
      However, analysis of patients with tumors originating from tissues that express
      the peptides in normal conditions could be of importance. The results from the
      meal test indicate that the hormone levels are affected by food intake in healthy
      individuals, whereas obestatin levels remained unchanged in pancreatic NET
      patients.

PMID- 23147275
TI  - An integrated secondary prevention group programme reduces depression in cardiac
      patients.
AB  - OBJECTIVE: Depression is common following an acute cardiac event and can occur at
      a time when behaviour change is strongly recommended to reduce the risk of
      further cardiovascular events. The 'Beating Heart Problems' programme was
      designed to support cardiac patients in behaviour change and mood management.
      METHODS: The programme was based on cognitive behaviour therapy and motivational
      interviewing. A randomized controlled trial (RCT) comparing the 8-week group
      programme with usual care was undertaken between 2007 and 2010. All patients
      attended a hospital-based clinic for assessment of physiological risk factors at
      baseline (6 weeks after their acute event), and at 4- and 12-month follow up.
      Psychological and behavioural indicators were assessed by self-report
      questionnaires. Of the 275 patients enrolled into the RCT, 42 (15%) had Beck
      Depression Inventory-II scores >13 at baseline. Treatment and control group
      comparisons were undertaken for this subgroup, using growth curve modelling and
      testing for group differences over time in psychological, physiological, health
      behaviour, and self-efficacy measures. RESULTS: Significantly greater
      improvements (p < 0.01) in depression symptoms and self-rated health were
      reported for the intervention group, as well as significantly larger gains in
      confidence in managing depression (p < 0.05) and anger (p < 0.01). Trends (0.05 <
      p < 0.10) for larger treatment group improvements were also seen for anxiety
      symptoms and confidence in managing anxiety. CONCLUSION: A group secondary
      prevention programme that integrates behavioural and mood management strategies
      leads to decreased depression, increased confidence, and improved health
      perceptions in depressed cardiac patients.

PMID- 23147276
TI  - SURF - SUrvey of Risk Factor management: first report of an international audit.
AB  - BACKGROUND: Despite the fact that subjects with established coronary heart
      disease (CHD) are at high risk of further events and deserve meticulous secondary
      prevention, current audits such as EUROASPIRE show poor control of major risk
      factors. Ongoing monitoring is required. We present a new risk factor audit
      system, SURF (Survey of Risk Factor management), that can be conducted much more
      quickly and easily than existing audit systems and has the potential to allow
      hospitals of all sizes to participate in a unified international audit system
      that will complement EUROASPIRE. Initial experience indicates that SURF is truly
      simple to undertake in an international setting, and this is illustrated with the
      results of a substantive pilot project conducted in Europe and Asia. METHODS: The
      data collection system was designed to allow rapid and easy data collection as
      part of routine clinic work. Consecutive patients (aged 18 and over) with
      established CHD attending outpatient cardiology clinics were included.
      Information on demographics, previous coronary medical history, smoking history,
      history of hypertension, dyslipidaemia or diabetes, physical activity, attendance
      at cardiac rehabilitation, cardiac medications, lipid and glucose levels (and
      HbA1c in diabetics) if available within the last year, blood pressure, heart
      rate, body mass index, and waist circumference were collected using a one-page
      data collection sheet. Years spent in full time education was added as an
      additional question during the pilot phase. RESULTS: Three European countries -
      Ireland (n = 251), Belgium (n = 122), and Croatia (n = 124) - and four Asian
      countries - Singapore (n = 142), Taiwan (n = 334), India (n = 97), and Korea (n =
      45) - were included in the pilot study. The results of initial field testing were
      confirmed in that it proved possible to collect data within 60-90 seconds per
      subject. There was poor control of several risk factors including high levels of
      physical inactivity (41-45%), overweight and obesity (59-78%), and ongoing
      smoking (15%). There were lower levels of individuals attending cardiac
      rehabilitation in Asia. More Europeans than Asians reached the low-density
      lipoprotein cholesterol target of <2.5 mmol/l (66 vs. 59%) reflecting differences
      in medication usage. However, blood pressure control was superior in Asia, with
      71% <140/90 compared with 66% of Europeans (NS). CONCLUSIONS: This phase of SURF
      has confirmed its ease of use which should allow wide participation and the
      collection of representative risk factor data in subjects with CHD as well as
      ongoing data collection to monitor secular trends in risk factor control.
      Notwithstanding that this is a pilot study, the results suggest that risk factor
      control, particularly for lifestyle-related measures, is poor in both Europe and
      Asia.

PMID- 23147278
TI  - Assessment of three commercial DNA extraction kits and a laboratory-developed
      method for detecting Cryptosporidium and Cyclospora in raspberry wash, basil wash
      and pesto.
AB  - Polymerase chain reaction (PCR) methods are often used to identify the parasitic
      protozoa Cryptosporidium parvum and Cyclospora cayetanensis in foods although
      little has been published regarding the efficacy of available DNA extraction
      methods. This study reviewed three commonly used commercial DNA extraction kits:
      FastDNA SPIN Kit for soil, QBiogene (FastDNA), UltraCleanTM Soil DNA Isolation
      Kit, MO BIO Laboratories (MoBio), and QIAamp DNA Mini Stool Kit, Qiagen (QIAamp),
      as well as a 'homebrew' Universal Nucleic Acid Extraction (UNEX) method. Washes
      from raspberry and basil as well as commercial pesto samples were seeded with
      5000, 500, or 50 C. parvum and C. cayetanensis oocysts. The protocols were
      assessed for: quantity and quality of the extracted DNA, time to completion,
      presence of PCR inhibitors and the percentage of samples correctly identified as
      positive for the two parasites. Real-time and conventional nested PCR assays were
      used to detect the seeded pathogens. Of the commercial kits, PCR results of
      samples extracted using FastDNA were statistically similar to QIAamp and both
      were superior to MoBio. Differences in PCR results among FastDNA, QIAamp and UNEX
      for detection of Cyclospora were not statistically significant although the UNEX
      method proved best with Cryptosporidium. Real-time PCR assays targeted the 18S
      rRNA and the hsp70 genes of C. cayetanensis; overall results were similar to
      those found using conventional nested PCR targeting the 18S rRNA gene.

PMID- 23147277
TI  - Effectiveness of treat-to-target strategy for LDL-cholesterol control in type 2
      diabetes: post-hoc analysis of data from the MIND.IT study.
AB  - BACKGROUND: The paper presents a post-hoc analysis of the intensity of
      dyslipidaemia care operated in the first 2 years of Multiple-Intervention-in-type
      2-Diabetes.ITaly (MIND.IT) study. DESIGN AND METHODS: MIND.IT is a multicentric,
      randomized, two-parallel arm trial involving 1461 type 2 diabetic patients at
      high cardiovascular (CV) risk. The study compares the usual care (UC) of CV
      prevention with a multifactorial intensive care (IC) approach aiming at achieving
      target values for the main CV risk factors according to a step-wise treat-to
      target approach. RESULTS: Proportion of patients on target for low-density
      lipoprotein cholesterol (LDL-C) was about 10% at baseline and increased
      significantly more with IC than UC (43 vs. 27%; p < 0.001). However, the majority
      (57%) of patients, in this intended intensively treated cohort, failed to achieve
      the proposed target. Average LDL-C decreased from 144 +/- 35 to 108 +/- 31 mg/dl
      with IC and from 142 +/- 28 to 118 +/- 32 with UC (p-for-interaction <0.0001). IC
      was associated with a significantly greater increase in statin prescription and
      lower withdrawal from treatment than UC (43 vs. 11% and 28 vs. 61%, respectively;
      both p < 0.001). However, the new treatments were characterized in both groups by
      the use of low starting doses (<= 10 mg of atorvastatin, equivalent dose in more
      than 90% of patients) without increase in case of missed target. CONCLUSIONS: The
      application of a multifactorial treat-to-target intervention is associated with a
      significant improvement in LDL-C beyond usual practice. However, the change in
      LDL-C appears to be more related to an increased number of treated patients and a
      decreased treatment withdrawal than to a true treat-to-target approach.

PMID- 23147279
TI  - Sliding genioplasty using fresh-frozen bone allografts.
AB  - OBJECTIVE To present our experience in the use of fresh-frozen human bone
      allograft as an interpositional grafting material for sliding genioplasty to
      correct chin deformities. METHODS Ten patients underwent sliding genioplasty
      using morcellized and corticospongious fresh-frozen human bone. Four patients
      underwent orthognathic surgery associated with genioplasty. Six patient underwent
      genioplasty associated with rhinoplasty. Panorex, lateral, and frontal
      cephalogram and computed tomographic scans have been performed for each case
      preoperatively and 12 months after surgery. One patient subsequently asked for
      plate removal, and with his consent, a bone biopsy specimen was obtained during
      the operation. RESULTS Stable aesthetic and functional results were observed in
      all cases. No infections occurred, and no bone resorption has been clinically or
      radiologically observed. CONCLUSION The use of fresh-frozen bone allograft
      reduces patient morbidity and operative time, providing a stable and excellent
      aesthetic result.

PMID- 23147280
TI  - Presurgical nasoalveolar molding orthopedic treatment improves the outcome of
      primary cheiloplasty of unilateral complete cleft lip and palate, as assessed by
      naris morphology and cleft gap.
AB  - We evaluated the effects of presurgical nasoalveolar molding (NAM) with an
      orthopedic appliance and compared them with a passive orthopedic method (Hotz
      plate, HP), focusing on the naris morphology and width of the alveolar and palate
      cleft gap. The subjects were 28 unilateral complete cleft lip and palate patients
      treated with primary cheiloplasty at Tsukuba University Hospital from 2004 to
      2011. Thirteen patients were treated preoperatively with NAM (NAM group), and 15
      with HP (HP group). The surgical outcome was assessed according to left-right
      naris symmetry, as measured by the area ratio, perimeter ratio, aspect a/u ratio
      (aspect ratio of the affected side/aspect ratio of the unaffected side), and
      Hausdorff distance. In addition, the alveolar and palate cleft width was measured
      at the times of orthopedic plate setting and primary cheiloplasty. The aspect
      ratio was significantly smaller in the NAM group than in the HP group before the
      operation. In both groups, the aspect ratio, perimeter ratio, and Hausdorff
      distance were significantly smaller after the operation than before. The width of
      the alveolar and palate cleft gap was significantly narrowed in the NAM group,
      and the cleft gap at the initiation of NAM correlated significantly with the
      Hausdorff distance after cheiloplasty. We found that NAM improved the form of the
      naris after primary cheiloplasty and decreased the palate cleft gap more
      effectively than HP and that the width of the palate cleft gap was correlated
      with the surgical outcome of the naris.

PMID- 23147281
TI  - Microtia and congenital aural atresia.
AB  - The purpose of this study was to show the clinical characteristics of microtia
      and congenital aural atresia cases in Turkey and to make the classification. For
      this purpose, records of 28 patients with microtia who were admitted to the ENT
      Clinic of Eskisehir Military Hospital, Turkey, between 1995 and 2011 and 3
      patients admitted to the ENT outpatient clinic of Kocaeli Derince Education and
      Research Hospital, Turkey, were analyzed retrospectively. Of the total 31
      patients with microtia (35 microtic ears), involvement of the right ear of 20
      patients (64.5%), the left ear of 7 patients (22.5%), and bilateral involvement
      in 4 patients (12.9%) were observed. There was a unilateral involvement in 27
      patients (87.1%). According to the Marx grading, 2 patients (5.7%) had grade 1
      malformation, 3 (8.6%) had grade 2 malformation, 29 (82.9%) had grade 3
      malformation, and 1 (2.9%) had grade 4 malformation (anotia). Although the
      characteristics of microtia vary in different population, the results in Turkey
      are consistent with those in the literature.

PMID- 23147282
TI  - Incidence of postoperative velopharyngeal insufficiency in late palate repair.
AB  - BACKGROUND: This was a study of patients with cleft palate who for various
      reasons have their first hospital visit for palatal repair at an older age in
      developing countries. The aims of this study were to investigate the incidence of
      postoperative velopharyngeal insufficiency in Chinese patients with late palatal
      repair and to determine the relative importance of age at palatoplasty, cleft
      type, surgical technique, and experience for clinical outcomes. METHODS: A cohort
      of 224 patients who underwent primary palate repair were studied retrospectively.
      Speech outcomes were evaluated based on the severity of hypernasality and nasal
      emission. The percentage of cases that required a second operation was recorded.
      The related factors were analyzed, and a logistic regression model was applied.
      RESULTS: The mean age at palatoplasty was 5.6 (SD, 4.6) years (age range, 2-24
      years of age); 29.9% of the cases required a second operation. Age at
      palatoplasty was the only significant contributing factor for the percentage of
      patients who needed a second surgery. Each additional year in age at palatoplasty
      was associated with a 10.8% increase in odds of requiring a second surgery (P =
      0.002; odds ratio, 1.108; confidence interval, 1.038-1.182). However, cleft type,
      surgical technique, and surgeon's experience did not influence clinical outcomes.
      CONCLUSIONS: Primary palate repair at older than 2 years resulted in acceptable
      clinical speech outcomes in our patient population, there was an increase in the
      incidence of postoperative velopharyngeal insufficiency with increasing age at
      the time of palatoplasty. There was no correlation with cleft type, surgical
      technique, or surgeon's experience.

PMID- 23147283
TI  - Effect of direct electric current on parietal bone osteogenesis.
AB  - INTRODUCTION: It has been shown that biphasic electric stimuli may be effective
      in stimulation of bone growth. This study aimed to evaluate the role of direct
      electric current on osteogenesis of the parietal bone in a canine model.
      MATERIALS AND METHODS: After surgical implantation of assembly involving 3
      electrodes in the parietal bones in 5 adult male dogs, 20-MA direct electric
      current was applied. As a control group, a neutral assembly was implanted on the
      contralateral side of the calvaria.After 45 days of implantation, through a
      second surgical procedure, the bone samples were taken off the implantation sites
      and subjected to histologic evaluation. The data were analyzed with SPSS 16
      software package (SPSS Inc., Chicago, IL) using Chi-squared and Fisher exact
      tests. RESULTS: The bony tissues from all tissue sample sites were viable.
      Foreign body reaction that was documented by the presence of giant cells was
      observed in all samples. Histologic evaluation of samples revealed no
      statistically significant difference with respect to inflammatory reaction, bony
      trabecular thickness, bone arrangement, and maturation among the 3 electrode
      types (P > 0.05). CONCLUSIONS: Direct electric stimulation of the parietal bone
      in this canine model revealed no statistically significant difference with
      respect to inflammatory reaction, bony trabecular thickness, bone arrangement,
      and maturation.

PMID- 23147284
TI  - Increasing bony contact and overlap with computer-designed offset cuts in free
      fibula mandible reconstruction.
AB  - BACKGROUND: The free fibula flap is the standard of care in mandibular
      reconstruction; however, procedural nuances continue to optimize results. More
      accurate and efficient osteotomies for graft insetting can be envisioned, which
      address the difficulty in obtaining a perfect match between the cut ends of the
      fibula and the mandible and the subsequent giving up of maximal bone contact. We
      propose a method of complementary offset osteotomies. The angled cuts were
      virtually planned using three-dimensional computed tomographic images. Optimal
      offset cuts maximized surface area contact and facilitated intraoperative
      repositioning in the setting of additional native bone margin requirement.
      METHODS: Using previously described protocols, three-dimensional virtual
      reconstructions of the facial skeleton and the fibula (average, series of five)
      were used to simulate osteotomies at 25, 30, 45, 60, 75, and 90 degrees to the
      long axis of the fibula. Complementary osteotomies were then simulated at the
      mandibular body just distal to the first molar in simulated free fibula
      reconstructions. Total area of apposing surfaces was calculated using computer
      aided design. The results from the 25-, 30-, 45-, 60-, and 75-degree cuts were
      compared with the conventional 90-degree cut. Resin-based mandibular osteotomy
      guides and a complementary fibula jig were manufactured using computer-aided
      design. Two representative clinical cases were presented to illustrate proof of
      principle and benefits. RESULTS: The total surface area of apposing fibula and
      mandible surfaces in a conventional 90-degree cut was 103.8 +/- 2.05 mm.
      Decreasing this angle to 75, 60, 45, 30, and 25 degrees yielded increased surface
      areas of 0.86%, 10.3%, 35.3%, 136.7%, and 194.3%, respectively. Cuts of 25
      degrees also allowed for adequate bony contact in the setting of additional
      margin requirements up to 2.77 cm. Complementary 45-degree cuts provided
      excellent bone-to-bone contact in a free fibula reconstruction using resin guides
      and a jig. This angle also facilitated access of the saw to the distal mandible.
      CONCLUSIONS: Virtual surgical planning is an increasingly recognized technology
      for optimizing surgical outcomes and minimizing operative time. We present a
      technique that takes advantage of the precision complementary osteotomies that
      this technology affords. By creating offset cuts, we can maximize bony contact
      and ensure adequate contact should additional margins or intraoperative
      adjustments be required. This flexibility maximizes the precision of
      premanufactured cutting guides, mitigates the constraints of sometimes
      unpredictable intraoperative environments, and maximizes bony contact.

PMID- 23147285
TI  - Staged reconstruction of infected dura mater using vascularized rectus abdominis
      muscle.
AB  - Alloplastic synthetic dura is widely used in dura mater reconstruction. Although
      the incidence of postoperative alloplastic dura infection is not common, the
      possibility of intractable postoperative wound infection despite appropriate
      antibiotic use exists. Rectus free flap is composed of well-vascularized muscle
      and fascial tissues. This flap is appropriate for volumetric replacement in large
      defects, whereas the fascia is appropriate for dura mater reconstruction. We
      report a case of successful reconstruction in a patient who had intractable
      postsurgical wound infection with staged operation using vascularized rectus
      muscle and fascial flap in a patient with meningioma reconstructed with
      alloplastic dura graft (Neuropatch; B. Braun Melsungen AG, Melsungen, Germany)
      and additionally achieved aesthetic results. In the first step, vascularized
      rectus fascia and muscle were transferred to contaminated reconstructed dura
      after craniectomy. The removed calvarial bone was banked to the abdominal donor
      site pocket after cleansing. Finally, in the second stage, cranioplasty was
      performed with the banked autologous calvarial bone.

PMID- 23147286
TI  - Soft tissue facial morphometry before and after total oral rehabilitation with
      implant-supported prostheses.
AB  - The objective of the current study was to assess a low-cost, noninvasive facial
      morphometric digitizer to assist the practitioner in three-dimensional soft
      tissue changes before and after oral rehabilitation. Twenty-two patients aged 45
      to 82 years, all with edentulous maxilla and mandible, were assessed both before
      and after receiving their definitive complete implant-supported prostheses (each
      received 4-11 implants in each dental arch; full-arch fixed prostheses were
      made). The three-dimensional coordinates of 50 soft-tissue facial landmarks were
      collected with a noninvasive digitizer; labial and facial areas, volumes, angles,
      and distances were compared without and with the prostheses. Dental prostheses
      induced significant reductions in the nasolabial, mentolabial, and interlabial
      angles, with increased labial prominence (P < 0.05, Wilcoxon test). Lip vermilion
      area and volume significantly increased; significant increments were found in the
      vertical and anteroposterior labial dimensions. The presence of the dental
      prostheses significantly (P < 0.001) modified the three-dimensional positions of
      several soft-tissue facial landmarks. In conclusion, the current approach enabled
      quantitative evaluation of the final soft-tissue results of oral rehabilitation
      with implant-supported prostheses, without submitting the patients to invasive
      procedures. The method could assess the three-dimensional appearance of the
      facial soft tissues of the patient while planning the provisional prosthetic
      restoration, providing quantitative information to prepare the best definitive
      prosthesis.

PMID- 23147287
TI  - New technique for correcting mild types of cryptotia:  elevate cavum conchae
      cartilage and suture to cranial periosteum.
AB  - We have developed a new technique for the treatment of mild types of cryptotia in
      which the cavum conchae cartilage was pulled superiorly and sutured it to the
      temporal bone to the temporal parietal junction periosteum securely. Then, the
      stitches for bolster fixation were inserted parallel to the auricular temporal
      sulcus and temporarily left untied. Our technique is easy to use and secures a
      firm bolster fixation, and the scar is hidden. We recommend it for the treatment
      of mild types of cryptotia.

PMID- 23147288
TI  - Reconstruction of postinfected scalp defects using latissimus dorsi perforator
      and myocutaneous free flaps.
AB  - In severe, infected scalp defects, locally available tissues are not sufficient
      for reconstruction and are often unhealthy. In this situation, healthy free
      tissue transfer offers abundant vascularity of uncompromised tissue that can
      control infections and a single-stage reconstruction. Between March 2002 and May
      2010, 18 patients (20 cases) underwent traumatic scalp defect reconstruction with
      coincident infections as follows: 16 cases of postcranioplasty infections with
      previous traumatic open skull fractures and 4 cases of traumatic defects with
      infections without cranioplasties. Eighteen patients underwent 20 latissimus
      dorsi free flaps: 8 cases were latissimus dorsi perforator flaps without muscle
      and 12 cases were latissimus dorsi myocutaneous flaps. The mean flap size was 214
      cm. All patients healed well during the follow-up period. A latissimus dorsi flap
      in the supine position is an alternative for reconstruction of scalp defects with
      postcranioplasty or traumatic infections.

PMID- 23147289
TI  - Role of allergy in primary acquired nasolacrimal duct obstruction.
AB  - OBJECTIVE: Our objective was to determine the role of allergy in primary acquired
      nasolacrimal duct obstruction. METHODS: A total of 41 patients were enrolled in
      the study, 41 of whom had primary unilateral acquired nasolacrimal duct
      obstruction. All patients included in the study were evaluated by anterior
      rhinoscopy, endoscopic nasal examination, and multiprick skin test to reveal
      allergic rhinitis. RESULTS: Allergy incidence was found to be high in study
      group. This was statistically significant (P < 0.05). CONCLUSIONS: Although
      primary acquired nasolacrimal duct obstruction seems to be an ophthalmologic
      problem, rhinologic problems have great importance in etiology. Detailed
      endoscopic examination and multiprick skin test will reveal the possible role of
      allergic rhinitis. This may increase the success rate both of the conservative
      treatment options and of the surgical treatment.

PMID- 23147290
TI  - Reconstruction of full-thickness nasal alar defects using cartilage-supported
      nonfolded nasolabial flaps.
AB  - The difficulties faced in the reconstruction of the nasal alar defects are still
      continuing because of their unique anatomy, free margin, and triple-layered
      complex structure. In this study, we would like to present the results of the
      cartilage-supported nonfolded nasolabial flap reconstruction method that we
      applied to full-thickness alar defects involving the alar rim. Between March 2009
      and October 2011, 5 patients with full-thickness alar defects underwent cartilage
      graft-supported nasolabial flap reconstructions. Three of the patients were men,
      whereas 2 patients were women. Their median age was 54.2 years (range, 43-62 y).
      The defects were caused by either tumor excision or trauma. According to the
      method we applied, cartilage grafts were placed into the pouches formed between
      the skin and the adipose tissue to provide cartilaginous support to the
      nasolabial flaps to be adapted to the defect areas. The deep surfaces that were
      going to form the nasal mucosa were grafted using postauricular full-thickness
      skin grafts. Patients were followed up for a median period of 7.3 months (range,
      3-21 mo). In all patients, the flaps fully fitted the defect areas and provided
      enough coverage over the defects. Although minimal graft contractions were
      observed in the later phase because of the cartilage support placed within the
      pouches formed in the flaps, no nasal airway constrictions were observed.The
      technique we applied is a simple and reliable method providing adequate framework
      support, full color and texture harmony, an open nasal passage, and a single
      session reconstruction in most cases.

PMID- 23147291
TI  - Human bone morphogenetic protein-2 use for maxillary reconstruction in cleft lip
      and palate patients.
AB  - BACKGROUND: The conventional methods of maxillary alveolar reconstruction in
      patient with cleft are the periosteoplasty and autologous bone grafting. As an
      important alternative of bone substitution, there is the recombinant human bone
      morphogenetic protein-2 (rhBMP-2). This study compares the rhBMP-2 with
      periosteoplasty and autologous bone grafting. METHODS: Patients with cleft and
      alveolar defect were divided into 3 groups of 6 patients who underwent to
      autologous iliac crest bone grafting, resorbable collagen sponge with rhBMP2, and
      periosteoplasty, respectively. The analysis was performed through computed
      tomographic scan preoperatively and at months 3, 6, and 12 postoperatively. The
      variables analyzed were the alveolar defect volume, formed bone volume, bone
      formation rate, maxillary height repair rate, and the formed bone density mean.
      RESULTS: The formed bone volume was similar comparing the bone graft and BMP
      groups at 1-year postoperative analysis (P = 0.58). Both of them had the formed
      bone volume significantly larger than the periosteoplasty group at 3 and 6 months
      postoperatively. In this last group, the 1-year follow-up was canceled because
      the bone formation was insufficient. The bone formation rate, the maxillary
      height repair rate, and the mean of density of the formed bone were similar in
      the bone graft and BMP groups at 1-year follow-up with P values of 0.93, 0.90,
      and 0.81, respectively. CONCLUSIONS: The amount of formed bone in the
      periosteoplasty group was insufficient. There was no difference among the bone
      graft and rhBMP-2 therapy considering the parameters analyzed.

PMID- 23147292
TI  - Treatment of giant basal cell carcinomas of the head and neck with aggressive
      resection and complex reconstruction.
AB  - Basal cell carcinoma is exceedingly common, but giant basal cell carcinomas
      (GBCCs) are rare. We retrospectively reviewed 34 patients with GBCC on the head
      and neck region treated with aggressive surgical excision and reconstruction in a
      single operative procedure.The large defects were reconstructed with 15 free
      tissue transfers and 20 pedicled muscle, musculocutaneous flaps, and skin flaps.
      We were able to observe 23 patients for a minimum 5 years after the surgery.
      Locoregional recurrence and/or distant metastasis were not observed in 22
      patients. Only 1 patient with the scalp BCC had local recurrence between the flap
      and the normal tissue 2 years after the surgery. Recurrent tumor was widely
      excised and reconstructed with a skin graft. Our results imply that low
      complications, good oncologic control, and acceptable cosmetic results can be
      achieved by a 1-stage team approach with aggressive surgical resection and
      reconstruction.

PMID- 23147293
TI  - Effectiveness of primary monocanalicularnasal intubation with Monoka tubes and
      nasal endoscopic findings for congenital nasolacrimal duct obstruction with
      enlarged lacrimal sac and chronic dacryocystitis.
AB  - BACKGROUNDS: We report successful outcomes of monocanalicularnasal intubation
      with Monoka tubes and endoscopic findings for Hasner valve area. This method is
      presented as a primary treatment modality in congenital nasolacrimal duct
      obstruction (CNLDO) with an enlarged lacrimal sac and chronic dacryocystitis.
      METHODS: In a prospective noncomparative consecutive case series, 23 eyes of 18
      patients with CNLDO with an enlarged lacrimal sac and chronic dacryocystitis
      underwent endoscopic probing and monocanalicularnasal intubation under general
      anesthesia. Demographic information, including age, sex, duration of preoperative
      symptoms, operative endoscopic findings, timing of silicone tube removal, follow
      up periods, complications, and outcomes, was analyzed. RESULTS: The study
      included 23 eyes of 18 patients. Mean (SD) age was 19.7 (12.2) months (range, 9
      48 mo). Under nasal endoscopic view, the probe tip protruded through a balloon
      like nasal mucosa around the Hasner valve. In all cases, tubes were removed in an
      office setting under topical anesthesia. Mean follow-up period was 24.6 (5.4)
      weeks. Complications, such as punctal slitting and corneal abrasion, were not
      observed. All patients showed successful results until the final follow-up.
      CONCLUSIONS: In cases of CNLDO with an enlarged lacrimal sac and chronic
      dacryocystitis, monocanalicular intubation is recommended rather than simple
      probing. Monoka tube intubation has the advantages of technical ease of insertion
      and tube removal. Moreover, the tubing does not threaten the unprobed part of the
      lacrimal drainage system. Endoscopic findings revealed that the probe tip
      protruded through a balloon-like nasal mucosa with pus around the Hasner valve.

PMID- 23147294
TI  - Hybrid distraction:  a novel method for distraction osteogenesis of the alveolar
      process.
AB  - Segmental distraction osteogenesis of the anterior alveolar process is a
      sufficient method to enlarge the alveolar arch. Indications for this method are
      dental crowding, retroalveolism, and leveling of the curve of Spee. However,
      after the distraction period, the anterior alveolar segment often shows an
      unfavorable inclination resulting in nonphysiologic load on the lower
      incisors.The aim of this paper was to introduce a new approach in segmental
      distraction osteogenesis of the anterior alveolar process. This new method
      combines 2 different surgical techniques: a segmental osteotomy for the alveolar
      ridge with instant fixation in the desired position and a distraction procedure
      for the alveolar segment. This hybrid distraction avoids an unfavorable
      inclination of the lower incisors after front-block distraction procedures.

PMID- 23147295
TI  - Effect of extracorporeal shock waves on subcondylar mandibular fractures.
AB  - OBJECTIVE: The purpose of this pilot study was to evaluate the effects of
      extracorporeal shock wave therapy on healing of subcondylar mandibular fracture
      in rats. METHODS: Unilateral subcondylar fracture in 20 Wistar albino rats was
      used as a fracture model. Each rat was anesthetized 1 day after surgery, and
      extracorporeal shock wave therapy was performed. On the 21st day after surgery,
      animals were killed. Mandibles were dissected, all soft tissues were removed
      after sacrifice, and fractured and nonfractured hemimandibles were obtained from
      each rat. Histologic analyses were performed by a single pathologist blinded to
      the samples. RESULTS: The specimens' mean score in bone fracture healing was 7
      (1.09) (range, 6-9) in group 1 and 2.57 (1.62) (range, 1-6) in group 2. With
      respect to the specimens' bone fracture healing score, there was a statistically
      significant difference between the 2 groups. CONCLUSIONS: As a result, our study
      showed that extracorporeal shock wave therapy accelerated the improvement of
      fractures in experimentally induced subcondylar mandibular fracture in the rat
      mandible. We believe that reducing the duration of improvement in subcondylar
      mandibular fractures by intermaxillary fixation along with extracorporeal shock
      wave theraphy would contribute to preventing complications such as ankylosis,
      fibrosis, and hypomobility occuring because of prolonged fixation.

PMID- 23147296
TI  - Lymphatic malformations in children and adolescents.
AB  - PURPOSE: This article aimed to present a series of surgically treated lymphatic
      malformations of the cervicofacial region in a population of children and
      adolescents during a 13-year period. METHODS: The medical records of all children
      and adolescents with cervicofacial lymphatic malformations, treated surgically at
      our department from 1998 to 2011, were reviewed retrospectively. RESULTS:
      Eighteen patients with 20 lymphatic malformations located within the soft tissues
      of the cervicofacial region were identified. All patients were submitted to
      surgical treatment (excision or resection with conventional scalpel or
      radiosurgery) to address complications (ulceration, bleeding, impaired
      mastication and feeding, airway obstruction) and/or aesthetic issues. Recurrence
      was noted in 2 of our patients. CONCLUSIONS: Accurate diagnosis based on history,
      clinical examination, and adequate imaging techniques is the key to the optimal
      treatment of cervicofacial lymphatic malformations; surgical intervention remains
      the treatment of choice for these lesions.

PMID- 23147297
TI  - Primary maxillomandibular advancement with concomitant revised
      uvulopalatopharyngoplasty with uvula preservation for severe obstructive sleep
      apnea-hypopnea syndrome.
AB  - BACKGROUND: This study aimed to evaluate the efficacy and safety of primary
      maxillomandibular advancement (MMA) with concomitant adjunctive revised
      uvulopalatopharyngoplasty with uvula preservation (H-UPPP) in selected patients
      with severe obstructive sleep apnea-hypopnea syndrome (OSASH). METHODS: Eleven
      consecutive male patients with velo-orohypopharyngeal and hypopharyngeal
      narrowing underwent MMA with concomitant H-UPPP for severe OSAHS. All patients
      underwent a physical examination, Epworth Sleepiness Scale evaluation,
      cephalometry, nocturnal polysomnogram, and velopharyngeal insufficiency
      questionnaire survey before and at 6 to 12 months after surgery. RESULTS: On the
      basis of the success criteria, defined as an apnea-hypopnea index less than 20
      and a decrease greater than 50%, the success rate was 91%. The apnea-hypopnea
      index decreased from 67.44 (13.30) to 9.41 (7.20) events per hour (P < 0.001) and
      the lowest oxygen saturation increased from 63.0% (10.70%) to 88.55% (4.59%) (P <
      0.001) after surgery. All patients showed a significant decrease in mandibular
      plane to hyoid bone and increase in PAS after surgery. One patient reported
      regurgitation of liquids when drinking hastily after surgery. Two patients
      reported regurgitation as occasional occurrences. Half a year later, 2 patients
      reported complete resolution of the symptoms. One patient still complained of
      rare regurgitation of liquids when drinking quickly. Five patients had
      paresthesia of the lower lip; in 4 patients, the paresthesia had resolved by 12
      months after surgery. One patient still complained of paresthesia of the lower
      lip after 2 years of follow-up. No major complication (eg, upper airway
      obstruction) occurred. CONCLUSIONS: Primary MMA with concomitant adjunctive H
      UPPP is effective in selected patients with severe OSAHS without major
      complications.

PMID- 23147298
TI  - Malignant otitis externa.
AB  - OBJECTIVE: Malignant external otitis is a severe infection of the external
      auditory canal and skull base, which most often affects elderly patients with
      diabetes mellitus. This disease is still a serious disease associated with
      cranial nerve complications and high morbidity-mortality rate. Malignant otitis
      externa requires urgent diagnosis and treatment. The most effective treatment is
      to control the diabetes and to fight infection with the proper antibiotic and
      debridement necrotic tissue; sometimes, aggressive surgical management is done.
      We present our 5-year institutional experience in the management of this disease.
      The aim of this study was to present our experience with the management of
      malignant otitis externa. METHODS: All patients' records with malignant otitis
      externa during the last 5 years (2007-2012) were retrieved and reviewed. Diabetes
      mellitus profile, erythrocyte sedimentation rate, ear swab for culture and
      sensitivity, computed tomography, and scintigraphy using technetium 99 and
      gallium 67 were investigated for all patients. RESULTS: During the last 5 years
      (2007-2012), 10 patients with the diagnosis of malignant otitis externa were
      admitted to our clinic for investigation and treatment. There were 7 men and 3
      women, all between 64 and 83 years of age, with severe persistent otalgia,
      purulent otorrhea, granulation tissue in the external auditory canal, and diffuse
      external otitis, and there were 4 patients with facial nerve palsy. Nine patients
      were confirmed to have a diabetes, and 4 of these 9 cases just had chronic renal
      failure and underwent dialysis; the remainder 1 case had no diabetes mellitus,
      but with chronic renal failure on dialysis. Ear swabs for culture and sensitivity
      usually revealed Pseudomonas aeruginosa. Local debridement and local and systemic
      antibiotic treatment were sufficient to control the disease. Facial nerve
      decompression was done in facial paralysis. Hyperbaric oxygen therapy was
      performed in facial nervy palsy cases. CONCLUSIONS: Malignant otitis externa is
      still a serious disease associated with cranial nerve complications and high
      morbidity-mortality rate. The most effective treatment is to control the diabetes
      and to fight infection with the proper antibiotic, debridement necrotic tissue,
      and sometimes aggressive surgical management. Monitoring of therapy response is
      done through normalization of erythrocyte sedimentation rate, control of diabetes
      mellitus, and improvement of computed tomography and radioisotope scanning.

PMID- 23147299
TI  - Endoscopic-assisted surgical correction for congenital muscular torticollis.
AB  - BACKGROUND: Various surgical approaches have been advocated to release, lengthen,
      or excise a segment of the sternocleidomastoid (SCM) muscle for the treatment of
      congenital muscular torticollis (CMT). However, all those conventional methods
      make noticeable scars on the clavicle or neck area. We proposed the endoscopic
      assisted postauricular approach for the treatment of CMT that provides good
      functional and cosmetic outcomes and less learning curve. METHODS: Endoscopic
      assisted release of the SCM muscle was performed in 15 children. Ages at
      operation ranged from 9 months to 6 years, with a mean of 17.6 months. The
      sternal and clavicular attachments of the SCM muscle were dissected and resected
      at 1-cm segments near to the insertion area, through the endoscopic view. To
      prevent relapse, neck splint was applied after operation for 6 months. RESULTS:
      The mean operative time was 40 minutes. During the procedure, great auricular
      nerve and spinal accessory nerve were preserved well and there were no
      complications. Follow-up for 6 months in all patients showed complete muscular
      release and satisfactory correction with no recurrence. The neck scars were not
      visible after the procedure. The incision scar was well obscured on the posterior
      auricular sulcus. CONCLUSIONS: Endoscopic correction for the CMT is a feasible
      and easy-to-learn procedure. This method is a safe and effective procedure that
      provides good functional and cosmetic outcomes.

PMID- 23147300
TI  - Evaluation of discectomy and dermis-fat grafting on the contralateral side.
AB  - PURPOSE: We investigated the effects of unilateral discectomy with an abdominal
      dermis-fat graft of the temporomandibular joint (TMJ) on the contralateral side.
      PATIENTS AND METHODS: A total of 14 patients who underwent unilateral TMJ
      discectomy and dermis-fat grafting for severe internal derangement in 2009 and
      2010 were included. Clinical parameters, such as maximum mouth opening and
      lateral movements of the mandible, were recorded preoperatively and at 1 year
      postoperatively. Preoperative and 1-year postoperative magnetic resonance imaging
      was conducted to determine the duration of the operated and unoperated TMJs.
      RESULTS AND CONCLUSIONS: All 14 patients showed improvement in the mandibular
      mobility and function. However, postsurgical disc displacement without reduction
      was observed on the unoperated TMJ in 1 patient. Another patient complained of
      crepitus on the operated TMJ. Primary occlusal contact on the operated side of
      occlusion was observed in 2 other patients. Maximum mouth opening and measured
      lateral movements had increased in all patients at 1 year after the operation.

PMID- 23147301
TI  - Transcutaneous reduction of frontal sinus fracture using bony tapper device.
AB  - PURPOSE: Frontal sinus fractures are relatively common injuries presenting to
      trauma units. The optimal treatment of frontal sinus fractures remains
      controversial. Bicoronal approach is commonly used to obtain full exposure of
      both frontal bones and to repair any intracranial trauma; however, this approach
      requires long operative time and could lead to a long-lasting visible scar,
      alopecia, and paresthesias. In addition, patients have to stay in hospital for
      several days with this method. Endoscopic approach, less invasive than bicoronal
      method, has a steep learning curve. In this article, we suggest a simple
      reduction method in frontal sinus anterior wall fracture using the tapper
      instrument. METHODS: Between 2005 and 2011, a transcutaneous reduction of closed
      anterior table frontal sinus fracture using a tapper instrument was performed in
      13 patients. This group consists of 10 men and 3 women, and the mean age was 27.5
      years. Under general anesthesia, the point that the tapper would be placed is
      marked considering the fracture site shown on computed tomographic scan and the
      clinically depressed area. A 3-mm slit incision was made just above the marked
      point. After drilling through this incision, the tapper device was applied to the
      depressed bone segment. Simply pulling out the tapper, the depressed frontal
      sinus anterior wall segment was reduced. RESULTS: Contour deformities were
      restored completely in all patients without any recurrent displacement, and all
      patients were satisfied with the results. There were no complications such as
      infection and uncontrollable sinus bleeding, but pneumocephalus had occurred in 1
      patient owing to the posterior table injury that happened during the tapper
      applying procedure. We treated him with preventive antibiotics, and he completely
      recovered after 1 week. CONCLUSIONS: This method has better aesthetic results,
      shorter operative time, and minimal hospital stay than other surgical approaches.
      Although it contains minimal risk of posterior wall injury, considering not only
      surgical results but also patients' satisfaction, the authors suggest that this
      simple percutaneous reduction method using the tapper instrument would be the
      treatment of choice in the frontal sinus anterior wall fractures.

PMID- 23147302
TI  - Minimally invasive surgery for coronoid hyperplasia:  endoscopically assisted
      intraoral coronoidectomy.
AB  - The term hyperplasia of the coronoid process of the mandible defines an abnormal
      elongation of the coronoid process consisting of histologically normal bone. The
      main clinical finding of hyperplasia of the coronoid process is a progressive
      painless difficulty in opening the mouth owing to the contact with the temporal
      surface of the zygomatic bone or medial surface of the zygomatic arch. Computed
      tomography with three-dimensional reconstruction is essential and is the gold
      standard for an accurate diagnosis. The etiology remains unknown, although
      several theories have been suggested. The main aim of treatment was to restore
      mouth opening, and this article introduces and illustrates the advantages of
      endoscopic assistance for coronoidectomy through the classic "intraoral" approach
      and emphasize this minimally invasive approach.

PMID- 23147303
TI  - Subconjunctival injection of triamcinolone for the treatment of upper lid
      retraction associated with thyroid eye disease.
AB  - Management of retraction of the upper lid during the congestive phase of thyroid
      eye disease is usually limited to conservative treatment. We evaluated the
      efficacy of subconjunctival injection of triamcinolone for the treatment of the
      upper lid retraction associated with thyroid eye disease.Thirty patients (43
      eyes, 11 men and 19 women) with the upper lid retraction associated with thyroid
      eye disease were evaluated between May 2009 and September 2010. A dose of 0.5 mL
      of triamcinolone acetonide (40 mg/mL) was injected into the subconjunctival space
      at the upper margin of the tarsus. If the upper lid retraction had not improved
      or was still severe 2 weeks after the initial injection, then triamcinolone was
      injected repeatedly at 2-week intervals. Photographs were taken before the
      injection and at the follow-up visit, and lid parameters including marginal
      reflex distance 1, interpalpebral fissure height, total palpebral fissure area,
      the upper nasal palpebral fissure area, and the upper temporal palpebral fissure
      area were measured. Changes in the lid parameters after the injection were
      evaluated.The mean number of injections per patient was 2.67, and the mean (SD)
      follow-up period was 260.97 (91.10) days. All lid parameters improved
      significantly after the triamcinolone injection (all P's < 0.05). Nineteen of 22
      patients in the congestive phase responded to the triamcinolone injection;
      however, 6 of 8 patients in the fibrotic phase did not respond to the
      triamcinolone injection. Complications associated with the triamcinolone
      injection included an increased intraocular pressure (2 patients) and a mild
      ptosis (1 patient).The subconjunctival triamcinolone injection is a simple and
      effective treatment option for the upper lid retraction associated with thyroid
      eye disease, and this treatment is more effective for the patients in the
      congestive phase.

PMID- 23147304
TI  - Septic arthritis of the temporomandibular joint.
AB  - Septic arthritis of the temporomandibular joint is a rare acute infectious
      disease that requires attention from physicians and, once misdiagnosed, can have
      several implications for a patient. The most common microorganisms related to
      this disease are Staphylococcus aureus, Neisseria, Haemophilus influenzae, and
      Streptococcus. The infection of the joint may be caused by a direct spread of a
      local infection or by hematogenous inoculation from a distant focus. General
      predisposing factors, such as immunodepression, can eventually be found. The aim
      of the current study was to report a case in which a patient with an articular
      infection resulting from hematogenous dissemination from a distant site was
      successfully treated using joint drainage and systemic antibiotics. Secretion
      culture from the temporomandibular joint space was positive for S. aureus. After
      1 month of antimicrobial therapy, the patient was asymptomatic and mandibular
      function was normal. Literature related to this topic was reviewed and discussed.

PMID- 23147305
TI  - CBCT combining with plaster models: application in virtual three-dimensional
      subapical segmental osteotomy to obtain more precise occlusal splint.
AB  - Anterior subapical segmental osteotomy is considered to be an important surgical
      technique to obtain functional occlusion and improve the facial profile for
      patients with maxillary and mandibular protrusion or retrusion, and some
      complications, such as ischemic necrosis of the distal segment, devitalization of
      the teeth adjacent to the osteotomy site, and inadequate movement space of
      segment for obtaining a good occlusion or facial profile, usually exist during
      surgery. Imprecise measurement of root length, interradicular distance, and
      intertooth distance based on traditional panoramic radiography that demonstrated
      existing horizontal distortion and vertical distortion may play an important role
      in resulting in these problems. In addition, the root is invisible for surgical
      simulation in traditional plaster models. The recently developed cone-beam
      computed tomography (CBCT) presents a higher spatial resolution with a lower
      radiation dose, simultaneously with excellent accuracy and without magnification
      of images. The presented technique was used to obtain a precise occlusal splint
      in virtual 3D subapical segmental osteotomy by combining CBCT with plaster models
      that could guarantee the measurement accuracy of root length, interradicular
      distance, and intertooth distance, followed by the result of fewer tooth root
      damage and more precise forecasting of available movement space of jaw segment.
      Combining with other advantages of virtual 3D surgery, such as precise teeth
      surface of plaster models, soft tissue simulation, genoplasty simulation, and
      zygoma plasty simulation, this presented technique may offer a preferable method
      to patients who need subapical segmental osteotomy.

PMID- 23147306
TI  - Midfacial degloving approach for resectioning and reconstruction of extensive
      maxillary fibrous dysplasia.
AB  - OBJECTIVE: The traditional unilateral or bilateral buccogingival or bicoronal
      approach often seems to impose limitations on achieving complete resection and
      reconstruction of the extensive midfacial fibrous dysplasia. Therefore, we
      hypothesized that the midfacial degloving approach could be used for the
      correction of maxillary fibrous dysplasia, which has been primarily used for
      paranasal sinus lesions or nasopharyngeal tumor. METHODS: The study involved 5
      maxillofacial fibrous dysplasia patients who underwent a midfacial degloving
      surgical procedure. There were 4 male patients and 1 female patient with a mean
      age of 16.8 years. The average, mean follow-up duration was 17.8 months. A wide,
      subperiosteal dissection was made along the anterior wall of the maxilla and
      pyriform aperture over the level of the infraorbital foramen. A bilateral,
      circumferential, nasal vestibular incision and dissection allowed for bilateral
      degloving of the middle third of the face over the infraorbital rim. Then total
      or subtotal resection, followed by reconstruction using an iliac bone graft, was
      performed. RESULTS: The midface, degloving approach provided visualization of the
      medial maxillary wall, the pterygoid junction, nasofrontal suture, infraorbital
      rim, and laterally to the temporal process of the zygoma. Subtotal or total
      resection of the lesions and reconstruction with bone grafts was possible in all
      5 patients, and there were no complications. There was also no visible facial
      scarring and all patients expressed satisfaction with the cosmetic outcome.
      CONCLUSIONS: The midfacial, degloving approach was found to be safe and effective
      for maxillofacial fibrous dysplasia, and nearly total resection was possible.
      This approach allows for a wider dissection and resection compared with the
      traditional buccogingival approaches, and there was no visible facial scarring.

PMID- 23147307
TI  - Surgical correction of progressive hemifacial atrophy with onlay bone graft
      combined with soft tissue augmentation.
AB  - OBJECTIVE: Moderate-to-severe Parry-Romberg syndrome involves progressive atrophy
      of facial bony structures as well as changes in skin and subcutaneous tissue. To
      correct facial asymmetry in PRS patients, it is important to restore facial bony
      alignment and obtain a symmetrical appearance. METHODS: The authors propose a new
      combination method of onlay bone grafting and adipofascial free flap. Applying
      this technique, we performed rib bone graft with concomitant free flap transfer
      in 10 patients. All patients showed moderate-to-severe findings of PRS, involving
      skull deformity. Both male and female were 4 and 6 patients each, and the age of
      the patients at which they received surgery ranged from 10 to 52 years, with an
      average of 24.8 years of age. During the follow-up period, ancillary procedures
      including dermofat graft and hyaluronic acid filler injections were performed to
      achieve fine facial contour and facial symmetry. RESULTS: There were no severe
      complications such as infection or postoperative bleeding. All patients were
      satisfied with the result, and postoperative CT scanning revealed successful
      uptake of grafted bone. CONCLUSIONS: Onlay frame bone graft by using rib bone as
      donor material, with combination of facial fat free flap transfer can be an
      excellent choice in restoring facial symmetry in severe cases of progressive
      hemifacial atrophy.

PMID- 23147309
TI  - Intraoral approach for removal of large sialolith in submandibular gland.
AB  - Sialolithiasis is a benign pathology that occurs most frequently in the
      submandibular salivary gland due to its anatomic features. Depending on the size
      and degree of calcification, a sialolith can be visible in radiographic
      examinations. Patients commonly experience pain and/or edema when the ducts are
      obstructed. The authors report two cases of sialolithiasis of the submandibular
      gland after searching for the source of swelling in the submandibular region. The
      diagnosis was confirmed by clinical and tomographic examinations. Despite the
      considerable size of the sialoliths, treatment consisted of the removal of the
      calcified mass using an intraoral surgical approach. The prognosis is often good
      and there is generally no recurrence of the condition.

PMID- 23147308
TI  - Radial forearm free flap with titanium mesh sandwich reconstruction in complex
      anterior skull base defects.
AB  - BACKGROUND: Skull base reconstruction presents a number of challenges from
      anatomical and functional perspectives. This is especially the case with large
      anterior skull base defects with compromised recipient beds from repeated
      infection, multiple surgeries, or previous radiation. The purpose of the study
      was to demonstrate the use of the titanium mesh/radial forearm free flap (RFFF)
      mesh sandwich for reconstruction of large anterior skull base defects with a poor
      recipient bed or excessive bony defect. METHODS: Retrospective case series of 3
      patients with complex anterior skull base defects reconstructed with a titanium
      mesh/RFFF mesh sandwich technique. RESULTS: Reconstruction of 3 cases using the
      titanium mesh/RFFF sandwich technique resulted in definitive treatment with no
      recurrent cerebral spinal fluid leaks, meningitis, or complications. CONCLUSIONS:
      The titanium mesh/RFFF sandwich is an excellent reconstructive option for large
      anterior skull base defects with a poor recipient bed. This approach is
      facilitated using a combined open and endonasal endoscopic approach in a
      multidisciplinary team composed of head and neck surgery, rhinology, and
      neurosurgery.

PMID- 23147310
TI  - Management of aplasia cutis congenita of the scalp.
AB  - BACKGROUND: Aplasia cutis congenita (ACC) is a rare condition commonly affecting
      the scalp in which there is a focal deficiency of cutaneous tissues of varying
      severity ranging from an absence of skin through to full thickness defects
      involving deeper elements such as bone and dura. Lesions of the scalp can be
      associated with complications including infection, hemorrhage, thrombosis, and
      seizures. Opinions in the current literature regarding management of this
      condition are varied with both conservative and surgical management advocated.
      Conservative treatment consists of regular wound dressings and systemic
      antibiotics, while surgical management commonly involves skin grafting and local
      flaps. METHODS: A retrospective case review was performed to audit the outcomes
      of patients with ACC of the scalp managed at the Women's and Children's Hospital
      (WCH) in Adelaide, Australia from 2002 to 2012. Cases were identified from
      admission coding diagnoses and data was retrieved from patient case notes.
      RESULTS: Seventeen cases of ACC were identified. The most common location
      involved was the scalp vertex. Thirteen patients were managed conservatively and
      4 had primary surgical intervention. Of the cases that were managed with primary
      surgery, 2 had complications. None of the conservatively managed patients had
      complications in the acute setting. CONCLUSIONS: At the WCH, we advocate adopting
      a conservative approach to management of ACC of the scalp. Defects can be
      successfully managed with a combination of regular dressings and systemic
      antibiotics. Regular wound monitoring is essential to detect any complications
      early to instigate appropriate treatment and determine the need for emergency
      surgical management.

PMID- 23147311
TI  - Frequency of surgical correction for maxillary hypoplasia in cleft lip and
      palate.
AB  - OBJECTIVE: The aim of this study was to determine the frequency of surgical
      correction of maxillary hypoplasia in individuals with nonsyndromic cleft lip
      and/or palate (CL/P) treated at the Center for Craniofacial Anomalies at
      University of California, San Francisco (UCSF). SUBJECTS: This is a retrospective
      cohort study of individuals with cleft lip and/or palate born between 1970 and
      1990 who were treated at the UCSF Center for Craniofacial Anomalies. Data were
      gathered from the UCSF Craniofacial Anomalies Filemaker Pro database. METHODS:
      From the database, we collected the following information: age, gender, cleft
      type, date of orthognathic surgery, and type of osteotomy. The subjects were
      further subcategorized by cleft type and gender. RESULTS: A total of 973
      individuals with a diagnosis of cleft lip and/or palate were reviewed: 325
      subjects had an associated syndrome and 648 were nonsyndromic. A total of 59 of
      these 648 nonsyndromic cleft individuals (9.1%) required surgical intervention
      for correction of maxillary hypoplasia: 2/105 (1.9%) for cleft lip, 4/122 (3.3%)
      for cleft palate, 35/286 (12.2%) for unilateral cleft lip and palate, and 18/135
      (13.3%) for bilateral cleft lip and palate. CONCLUSIONS: The frequency of
      surgical correction for maxillary hypoplasia in cleft individuals at UCSF Center
      for Craniofacial Anomalies at 9% was lower than the reported average of 25%.

PMID- 23147312
TI  - Reconstruction of large anterior scalp defects using advancement flaps.
AB  - Reconstruction of the scalp may be challenging for reconstructive surgeons
      because of the special anatomic structure of the scalp and underlying skeleton.
      Anterior scalp defects especially deserve special care for pleasant hairline re
      creation and redirection of hair follicles. Local transposition or rotation flaps
      are the most common reconstruction methods for moderate or large anterior scalp
      defects. However, currently available techniques usually require multiple stages
      for completion of the reconstruction without alopecia.In this study, we report
      our experience with unilateral or bilateral advancement flaps for moderate or
      large anterior scalp defect reconstructions. Eight patients who had anterior
      scalp defect of varying etiology were presented. The defect size ranged between 3
      * 5 and 8 * 12 cm. The average size of the defect was 53. 3 cm. The defects were
      located on the frontoparietal area of the scalp in 3 patients and frontal area in
      5 patients. Unilateral advancement flap was used in four cases. All the flaps
      survived except in one patient who had partial flap loss. Based on our
      experience, we suggest that large scalp defects located especially on the frontal
      or frontoparietal area can be reconstructed with unilateral or bilateral scalp
      advancement flaps in one stage without the need for multiple surgeries.

PMID- 23147313
TI  - Unilateral cleft nasal deformity correction using conchal cartilage lily flower
      graft.
AB  - We present a conchal cartilage lily flower graft for correcting depressed and
      laterally displaced alar cartilage for correction of unilateral cleft nasal
      deformity.After making a V incision at the base of the columellar and then
      marginal incisions, the alar cartilages were exposed. A fusiform-shaped cartilage
      larger than 2.5 cm in length and 1 cm in width was obtained. The midline long
      axis was scored with a No. 15 knife, and the lateral one third was split. Two
      thirds length portions were folded in half, and they became straightened in the
      shape of a stalk of a lily flower. Two symmetrical one-third length portions were
      fanned out bilaterally in the shape of the leaf of a lily flower. The stalk
      portion was positioned in a pocket between the medial crura, and the 2 leaf
      portions were placed on the dome of the alar cartilages. The marked points of the
      cleft side and contralateral side were secured with sutures. The V incision at
      the base of the columellar and the marginal incisions were closed with a V-Y
      shape. In this technique, the 2 leaf portions were placed on the dome of the alar
      cartilages and sutured; therefore, the suture holds the dome of the cleft side to
      the contralateral side without peaking.Thirteen patients (6 male and 7 female
      subjects; age range, 13-30 years) were operated. Among them, 6 patients were very
      satisfied, and 5 patients were satisfied with the results. Two patients felt they
      were improved.We think the conchal cartilage lily flower graft might be a good
      method for correction of depressed and laterally displaced alar cartilage in
      unilateral cleft nasal deformity.

PMID- 23147314
TI  - Functional reconstruction with an extended supraclavicular fasciocutaneous island
      flap following ablation of advanced oropharyngeal cancer.
AB  - The aim of the present study was to evaluate the functional outcome of an
      extended supraclavicular fasciocutaneous island flap for reconstructing
      oropharyngeal defects.The 15 patients with oropharyngeal cancers ranged in age
      from 54 to 73 years. Primary tumor excisions via a transmandibular approach and
      neck dissection were performed in all patients. An extended supraclavicular
      fasciocutaneous island flap with a flap skin paddle ranging in size between 4 *
      10 and 6 * 12 cm was used to reconstruct the defects.All of the flaps survived.
      Minor flap failure occurred in 2 cases, and 1 of these developed a minor
      orocutaneous fistula. All patients could eat soft foods and had normal speech.
      The extended supraclavicular fasciocutaneous island flap is a simple, reliable
      flap that can be used for functional reconstruction of oropharyngeal defects.

PMID- 23147315
TI  - Late correction of orbital-zygomatic-maxillary fractures combined with orbital
      wall fractures.
AB  - PURPOSE: With the increasing number of patients with facial trauma, orbital
      zygomatic-maxillary (OZM) fracture combined with orbital wall fracture has become
      common. Such fractures always induce symptoms of enophthalmos, hypoglobus, and
      diplopia. This study was aimed to investigate the surgical technique and
      operative effect of late reconstruction of OZM fractures combined with orbital
      wall fractures. METHODS: A retrospective analysis of the 46 patients (46 orbits)
      who were treated from January 2005 to December 2008 was performed. All cases had
      reconstruction of OZM fractures combined with orbital wall fractures at an
      average of 5.3 months after injury. Various incisions were selected. According to
      the computer-aided design/computer-aided manufacturing design, the osteotomy,
      reposition, and 4-point fixation of the fractured bones were individualized
      performed. Titanium mesh was preshaped according to the mirroring technology and
      inserted into the orbit with or without high-density polyethylene (HDPE) implant
      material to repair the orbital wall defect and the enlarged orbital volume. All
      patients were followed up 1 year after surgery. RESULTS: Forty-two of the 46
      patients who had enophthalmos were completely corrected. Forty patients who had
      hypoglobus were corrected postoperatively. Of the 43 cases with diplopia, 20
      cases were resolved. CONCLUSIONS: Late reconstruction by osteotomy and 4-point
      fixation could recover midface cosmesis, correct the enophthalmos, and improve
      the diplopia of OZM fractures combined with orbital wall fractures. The computer
      aided design/computer-aided manufacturing system and mirroring technology can
      help improve the outcome of surgery when repairing such fractures.

PMID- 23147316
TI  - Effects of secondary porous orbital implantation in anophthalmic sockets.
AB  - AIMS: Our objective was to evaluate the effects of secondary porous orbital
      implantation 10 years after the primary evisceration in anophthalmic patients.
      PATIENTS AND METHODS: This study is a retrospective case series. Secondary
      orbital implant insertion was performed for 25 anophthalmic patients (25 eyes)
      who had experienced primary evisceration more than 10 years earlier. Under
      general anesthesia, secondary enucleation removing the contracted sclera,
      including the optic nerve, was performed, and diverse types of porous orbital
      implants were inserted. After surgery, changes in the socket and ocular
      prosthesis motility, and improvements in esthetic appearance were evaluated.
      RESULTS: For 24 of the 25 eyes, the patients were satisfied. In 17 eyes, ocular
      motility was higher than "fair" and showed improvement. Deep superior sulcus
      deformity was improved to "good" in 8 eyes, and enophthalmos was improved to
      "fair" in 15 eyes. Combined procedures to correct lid malposition and fornix
      contracture were successful, and these additional operations to correct the
      prolonged complications of anophthalmos might have reduced the frequency of
      implant exposure. CONCLUSIONS: In older anophthalmic patients with considerable
      concomitant socket contracture and cosmetic concerns, secondary porous orbital
      implant insertion may improve esthetics and the motility of the ocular
      prosthesis.

PMID- 23147317
TI  - Reconstruction of the mandible bone by treatment of resected bone with
      pasteurization.
AB  - The results of long-term follow-up for reimplantation of the mandibular bone
      treated with pasteurization are reported. Mandibulectomy was performed for
      mandibular malignancy in 3 cases. The resected bones were subsequently
      reimplanted after treatment with pasteurization in 3 cases to eradicate tumor
      cells involved in the resected bone. Although postoperative infection was
      observed in 2 of 3 cases, reimplantation of the resected mandibular bone treated
      by pasteurization was finally successful. Ten to 22 years of follow-up was
      carried out. Pasteurization was able to devitalize tumor cells involved in the
      resected bone and to preserve bone-inductive activity. Reimplantation of
      pasteurization could be a useful strategy for reconstruction of the mandible in
      patients with mandibular malignancy.

PMID- 23147318
TI  - Inferior alveolar nerve injuries associated with mandibular fractures.
AB  - The study evaluates the incidence of inferior alveolar nerve injuries in
      mandibular fractures, the duration of their recovery, and the factors associated
      with them. Fifty-two patients with mandibular fractures involving the ramus,
      angle, and body regions were included in this study; the inferior alveolar nerve
      was examined for neurological deficit posttraumatically using sharp/blunt
      differentiation method, and during the follow-up period the progression of neural
      recovery was assessed. The incidence of neural injury of the inferior alveolar
      nerve was 42.3%, comminuted and displaced linear fractures were associated with
      higher incidence of inferior alveolar nerve injury and prolonged recovery time,
      and recovery of inferior alveolar nerve function occurred in 91%.Fractures of the
      mandible involving the ramus, angle, and body regions, and comminuted and
      displaced linear fractures are factors that increase the incidence of inferior
      alveolar nerve injuries. Missile injuries can be considered as another risk
      factor.

PMID- 23147319
TI  - Effects of facial hard tissue surgery on facial aesthetics:  changes in facial
      content and frames.
AB  - Aesthetic units of the face can be divided into facial content (FC; eyes, nose,
      lips, and mouth), anterior facial frame (AFF; a contour line from the trichion,
      the temporal line of the frontal bone, the lateral orbital rim, the most lateral
      line of the anterior part of the zygomatic body, the anterior border of the
      masseter muscle, to the inferior border of the chin), and posterior facial frame
      (PFF; a contour line from the hairline, the zygomatic arch, to the ramus and
      gonial angle area of the mandible). The size and shape of each FC and the balance
      and proportion between FCs create a unique appearance for each person. The facial
      form can be determined through the combination of AFF and PFF. In the Asian
      population, clinicians frequently encounter problems of FC (eg, acute nasolabial
      angle, protrusive and everted lips, nonconsonant lip line, or lip canting), AFF
      (eg, midface hypoplasia, protrusive and asymmetric chin, vertical
      deficiency/excess of the anterior maxilla and symphysis, or prominent zygoma),
      and PFF (eg, square mandibular angle). These problems can be efficiently and
      effectively corrected through the combination of hard tissue surgery such as
      anterior segmental osteotomy, genioplasty, mandibular angle reduction,
      malarplasty, and orthognathic surgery. Therefore, the purposes of this article
      were to introduce the concepts of FC, AFF, and PFF, and to explain the effects of
      facial hard tissue surgery on facial aesthetics.

PMID- 23147320
TI  - Transverse rectus abdominis myocutaneous flap combined with vascularized costal
      cartilages in cranial reconstruction.
AB  - Exposing the alloplastic materials after skull reconstruction is very difficult
      because of the risk of infection and the choice of reconstruction procedures.
      Conventional procedures were divided into two-step or multi-step surgery.To
      perform one-stage surgery, a transverse rectus abdominis myocutaneous flap
      combined with vascularized costal cartilages has been used for head
      reconstruction after exposing the alloplastic materials in two patients. This is
      the first report using the flap for skull reconstruction.In this article, we
      describe the usefulness and the disadvantages of the transverse rectus abdominis
      myocutaneous flap combined with vascularized costal cartilages.

PMID- 23147321
TI  - Different techniques in fabrication of ocular prosthesis.
AB  - INTRODUCTION: Loss of an eye caused by cancer, trauma, or congenital defect
      creates a deep psychological impact on an individual's life especially social and
      professional life. Custom-made prosthesis, compared to stock prosthesis, provides
      a better fit to the eye socket, better cosmetic results, and less discomfort to
      the patient in the long term. The main objective of this article was to describe
      3 different alternative and practical techniques of fabricating custom-made
      ocular prosthesis. CASE REPORT: An impression of anophthalmic socket was made
      with the addition of cured silicone-based precision impression material in all
      techniques. A master cast was prepared and duplicated with condensation silicone.
      A self-cure acrylic resin was polymerized in the silicone model and was fitted
      into the patient's eye socket. A digital photograph of the patient's iris was
      made using a digital camera and printed on good-quality photo paper in various
      shades and sizes in the first and the second techniques. Then the photo paper was
      coated with PVC so as not to allow any color flowing. The proper iris was then
      inserted to the acrylic base. The prosthesis was final processed using
      orthodontic heat polymerizing clear acrylic resin.In the other technique, after
      the trying-in process with wax pattern, an acrylic base was fabricated using heat
      polymerizing scleral acrylic resin. The prosthetic iris was fabricated from a
      transparent contact lens by painting the lens with watercolor paints and
      attaching it to an acrylic resin with tissue conditioner. The final process was
      made with heat polymerizing transparent acrylic resin. CONCLUSIONS: Custom-made
      prosthesis allows better esthetic and functional results to the patient in
      comparison to stock prosthesis. Further follow-up is necessary to check the
      condition and fit of the ocular prosthesis in such patients.

PMID- 23147322
TI  - Double consecutive retrobulbar hemorrhage in a high-risk patient in treatment
      with aspirin and warfarin.
AB  - Retrobulbar hemorrhage is a vision-threatening emergency that may occur
      spontaneously or following facial trauma, orbital surgery, endoscopic sinus
      surgery, and retrobulbar injections. It may determine visual loss because of
      central retinal artery occlusion, optic neuropathy from direct compression, or
      compression of the circulation from mechanical tamponade. In addition to a
      deterioration in visual acuity with total blindness in the most severe cases,
      several symptoms and signs can be found, such as a sudden onset of severe pain,
      proptosis, and ophthalmoplegia.The knowledge of past medical history and
      underlying medical conditions is crucial in patients with retrobulbar
      hemorrhages. In fact, patients with blood dyscrasias have to be considered high
      risk patients due to their increased propensity for uncontrolled bleeding.The aim
      of this article was to present and discuss the management of a case of double
      consecutive retrobulbar hemorrhage in a high-risk patient in treatment with
      aspirin and warfarin.

PMID- 23147323
TI  - Management of facial trauma in patients older than 75 years.
AB  - According to the literature and World Health Organization, elderly people are
      specified as persons older than 65 years of age. The authors believe that the
      indication for surgery patients over 65 is based on the restoration of
      functionality and the aesthetics. The behavior of the surgeon has to change with
      patients aged older than 75 years where the restoration of function and,
      therefore, a good quality of life is far more important than the aesthetic
      restoration. In a retrospective study of 1022 patients consecutively hospitalized
      at Maxillofacial department in Roma, Universita "Sapienza," the patients older
      than 75 years were analyzed. During this period, the data of all patients
      undergoing treatment because of trauma-related injuries were collected. Data were
      registered regarding etiology, localization of the injury, surgical treatment
      ratio, medium average stay, age, and sex distribution. Surgical treatment in
      these patients should be driven by the general condition of health whenever
      possible; reduction of facial fractures should be guided by the need to return a
      good quality of life for the patients. The goal of this study was to analyze a
      new group of population, people older than 75 years, that is, a real new and
      growing group of population.

PMID- 23147324
TI  - One-stage reconstruction of a concha-type microtia using remnant tissue.
AB  - Microtia can be mild or severe. Although traditional reconstruction is suitable
      for classic microtia, reconstruction with minimal morbidity may be advantageous
      in selected cases.A 36-year-old man presented with concha-type microtia in which
      the cephalic portion of the helix and the helical root were absent and a
      relatively prominent antihelix was connected to the tragus. We exposed the buried
      helical cartilage and reinforced it with a V-Y advancement flap from the scalp.
      The most prominent portion of the helical rim was reconstructed using the tragus,
      and a skin tag was used to reconstruct the tragus.There were no complications and
      the patient was satisfied with the appearance of the reconstructed
      ear.Reconstruction with remnant tissue is not possible in all cases and the
      result can be unsatisfactory. However, it can be accomplished in 1 or 2 stages
      with minimal morbidity and no donor site scars, and the reconstructed ear has
      normal sensation.

PMID- 23147325
TI  - Neoclassical facial canons in young adults.
AB  - BACKGROUND: Facial proportional analysis is commonly used in the preoperative
      planning as well as in consultation for aesthetic and reconstructive operations.
      Neoclassical canons, introduced by Ancient Greeks, have been used to describe the
      facial morphological features for many years. In this paper, the validity of 7
      neoclassical canons was tested in young adult Greeks. The frequency and kind of
      variations were noted. MATERIALS AND METHODS: Direct anthropometric landmarks,
      obtained from 163 volunteer subjects, were used to test the neoclassical canons
      of the Greek face. These measurements produced 7 neoclassical canons: the 3
      section facial profile canon (tr-n=n-sn=sn-gn), the naso-aural proportion canon
      (n-sn=sa-sba), the naso-aural inclination canon, the orbital canon (en-en=ex-en),
      the orbitonasal canon (en-en=al-al), the naso-oral canon (ch-ch=1+1/2 al-al), and
      the nasofacial canon (al-al=1/4 zy-zy). Results were compared with North American
      Caucasians published in a previous study. RESULTS: A significant difference was
      found between genders in the orbital proportion canon, the orbitonasal canon, and
      the nasofacial and the naso-oral proportion canon. The difference between the 2
      races was demonstrated in the orbitonasal proportion canon, the naso-aural
      inclination canon, and the dominant variation of the naso-oral proportion canon.
      The mean frequency of all valid canons was greater in White Americans than in
      Greeks but similar among Greek genders. CONCLUSIONS: In the majority of Greeks,
      the neoclassical canons were not valid. In absence of valid proportion indices,
      this study offers surgeons guidance in assessing facial characteristics of Greek
      patients in preparation for corrective surgery and evaluation of postoperative
      results.

PMID- 23147326
TI  - Efficacy of biodegradable synthetic polyurethane foam for packing nasal bone
      fractures.
AB  - BACKGROUND: Nasal bone fracture is the most common traumatic disease among facial
      bone fractures. General treatment of this trauma is closed reduction, followed by
      intranasal packing. Vaseline or Furacin roll gauze, and Merocel are commonly used
      packing materials, but the pain produced while removing the packing is fearful
      for the patients. To compensate for this shortcoming, there has been an increased
      use of biodegradable synthetic polyurethane foam (SPF) recently. We performed a
      retrospective review to analyze the effectiveness of SPF after the closed
      reduction of nasal bone fracture. PATIENTS AND METHODS: A retrospective review
      was conducted in 109 patients who underwent closed reduction for pure nasal bone
      fracture. One group was packed with Furacin roll gauze and the other was packed
      with SPF. Postoperative pain, hemostatic effect, supporting ability on the
      fractured segment, and healing of the injured nasal mucosa were compared between
      the 2 groups. RESULTS: A total of 109 patients were reviewed, with 61 patients
      packed with Furacin roll gauze (group A) and 48 patients packed with SPF (group
      B). Between the 2 groups, only visual analogue scale of pain at postoperative
      fourth day was statistically low in group B (P = 0.045) with other parameters
      showing no statistical difference. DISCUSSION: Nasal packing after closed
      reduction of nasal bone fractures support the reduced fractured bony segment and
      also has the main role on hemostasis and healing of mucosal injury. Removal of
      the packing is painful and fearful to the patients. SPF as nasal packing material
      provides superior outcome in terms of pain and satisfaction and, at the same
      time, is not inferior to the conventional packing materials with regard to
      bleeding control, mucosal wound healing, toxicity, and stability of reduced
      fracture segment.

PMID- 23147327
TI  - Submental endotracheal intubation:  a valuable resource for the management of
      panfacial fractures.
AB  - Modern techniques for surgical treatment of midfacial and panfacial fractures in
      maxillofacial trauma lead to special problems for airway management. Usually, in
      perioperative management of panfacial fractures, the surgeon needs to control the
      dental occlusion and nasal pyramid assessment. For these reasons, oral and nasal
      endotracheal intubations are contraindicated for the management of panfacial
      fractures. Tracheotomy is considered by many as the preferred route for airway
      management in patients with severe maxillofacial fractures, but there are often
      perioperative and postoperative complications concerning this technique. The
      submental route for endotracheal intubation has been proposed as an alternative
      to tracheotomy in the surgical management of patients with panfacial fractures,
      besides it is accompanied by low morbidity. Thus, this paper aimed to describe
      the submental endotracheal intubation technique in a patient experiencing
      panfacial fracture. The subject was well treated using the submental endotracheal
      intubation to get good reconstruction of the fractures because the authors
      obtained free access of all facial fractures.

PMID- 23147328
TI  - Endoscopic surgery of cavernous sinus tumors originating from the extradura.
AB  - In the present study, we explored the effects of various endoscopic approaches in
      patients with cavernous sinus (CS) tumors. Five endoscopic approaches, including
      the endoscopic transseptal transsphenoidal approach, extended endoscopic
      transseptal transsphenoidal approach, extended transnasal transmaxillary
      approach, extranasal extended maxillary sinus approach, and endoscopic transnasal
      transpterygoid approach, were selected for the resection of CS tumors from 36
      patients. Thirty gross total tumors and 6 subtotal tumors were removed. After a
      follow-up period of 6 months to 3 years, 30 patients were determined to be
      recurrence-free, and 2 patients had unchanged residual tumors. One patient with a
      recurrent pituitary adenoma underwent a second surgery, and 1 patient with
      chordoma died because of an intracavernous carotid artery rupture 18 months after
      the operation. Various endoscopic approaches tailored to the origin and extent of
      the CS tumor were proven efficacious for the maximal and precise removal of CS
      tumors while avoiding vital structures.

PMID- 23147330
TI  - Optimization of curvilinear mandible distraction using 3-dimensional computer
      simulated modeling.
AB  - PURPOSE: Multi-vector distraction osteogenesis has been described for use in the
      reconstruction of complex mandible deformities. Using 3-dimensional computer
      simulation, the location of the osteotomy and arc of the device can be
      predetermined, allowing for precise planning and determination of end points.
      Here, we discuss our experience using this technique and propose methods to
      optimize outcomes and minimize discrepancies in the projected results. METHODS:
      Three patients who underwent curvilinear mandible distraction and preoperative
      computer-simulated planning are described. After simulation to determine level of
      osteotomy and arc of the curvilinear distractor device, design-specific guides
      were constructed. Intraoperatively, custom guides were used to precisely perform
      the osteotomy and for placement of each distractor. After the completion of
      distraction and device removal, the correlation of distraction end points,
      occlusion, and the volumes of the mandibles were analyzed. RESULTS: A vertical
      difference of 2.6 mm (shorter) from the proposed final position and an 8-mm
      sagittal difference (under correction) were seen in the first patient. In the
      second patient, the final position had a vertical difference of 5.7 mm (shorter)
      and a sagittal difference of 14 mm (undercorrected). In the third patient, after
      first simulating anterior rotation of the condyle before osteotomy and vector
      design, the final and simulated end points differed approximately 0.6 mm
      vertically (shorter) and 4.3 mm sagittally (undercorrected) CONCLUSIONS:
      Preoperative 3D simulation and planning is a useful adjunct in curvilinear
      mandible distraction; however, the forces of the muscles of mastication and the
      restrictive soft tissue envelope must be accounted for in the design to achieve
      precise end results.

PMID- 23147329
TI  - Hemodynamic changes comparing lidocaine HCl with epinephrine and articaine HCl
      with epinephrine.
AB  - BACKGROUND: The aim of the present study was to analyze hemodynamic changes after
      the administration of either 2% lidocaine with epinephrine 1:100,000 (L100) or 4%
      articaine with epinephrine 1:200,000 (A200) in the surgical removal of
      symmetrically positioned lower third molars. METHODS: A prospective, randomized,
      double-blind, clinical trial was carried out involving 43 patients. Each patient
      underwent 2 surgeries on different occasions-one under local anesthesia with L100
      and the other with A200. The following parameters were assessed at 4 different
      times: systolic, diastolic, and mean blood pressure; heart rate; oxygen
      saturation; rate pressure product (RPP); and pressure rate quotient (PRQ).
      RESULTS: No hypertensive peak was observed in systolic, diastolic, and mean blood
      pressure at any evaluation time. Moreover, the type of anesthetic solution did
      not affect diastolic blood pressure, oxygen saturation or PRQ during the
      surgeries. Statistically significant differences between groups were detected
      with regard to heart rate and RPP (P < 0.05). CONCLUSIONS: The epinephrine
      concentration (1:100,000 or 1:200,000) and local anesthetic solutions used (2%
      lidocaine or 4% articaine) influenced hemodynamic parameters without perceptible
      clinical changes in healthy patients undergoing lower third molar removal.

PMID- 23147331
TI  - Obstructive airway compromise in the early postoperative period after
      orthognathic surgery.
AB  - Between January 1, 1989 and April 30, 2012, approximately 2164 consecutive
      patients were treated with orthognathic surgery at the St. John's Hospital, Genk,
      Belgium. They all underwent a mandibular, maxillary, or bimaxillary osteotomy,
      performed by one of the 3 resident maxillofacial surgeons at the St. John's
      hospital in Genk. The purpose of the review was to investigate the incidence of
      major airway difficulties occurring postoperatively because of surgically related
      causes. It seemed that obstructive airway compromise was the only reason for
      urgent intervention to protect or to restore the airway. In total, 3 urgent
      unanticipated life-saving reintubations were attempted. One was successful, and
      the other was changed into an urgent tracheostomy. No deaths occurred in this
      patient series after orthognathic surgery. Osseous genioplasties, as stand-alone
      surgery or in combination with other simultaneous orthognathic procedures, do
      care the risk for a life-threatening respiratory distress because of a hematoma
      of the floor of the mouth, when performed with an oscillating saw or a surgical
      drill. If so, this probably will happen within the first 4 postoperative hours
      according to the experience in our series. This risk can be avoided by using a
      piezosurgical unit to perform the osseous genioplasty.

PMID- 23147332
TI  - Influence of frontosphenoidal suture synostosis on skull dysmorphology in
      unicoronal suture synostosis.
AB  - Severity of the Harlequin deformity seen in unicoronal synostosis may be
      augmented when frontoparietal suture synostosis has an associated fusion of the
      frontosphenoidal suture or in cases of isolated frontosphenoidal synostosis. The
      purpose of the current study is to characterize various suture fusion patterns
      along the coronal ring using a modified orbital index (MOI), orbital angle (OA),
      and endocranial base (EB) angle.This study is a retrospective single institution
      cohort study. Charts were reviewed over the past 12 years; patients with isolated
      UCS were included. MOI, OA, and EB were used to identify 3 groups of UCS
      patients.Twenty-one patients were identified for inclusion in skeletal
      dysmorphology analysis using MOI, OA, and EB measures. Frontoparietal synostosis
      patients were diagnosed at significantly younger ages than frontoparietal +
      frontosphenoidal patients (P = 0.0001). Ipsilateral MOI measures were more severe
      for frontoparietal patients compared with frontoparietal + frontosphenoidal
      patients (P = 0.0239). There was a trend for more severe ipsilateral OA measures
      in frontoparietal patients compared with frontoparietal + frontosphenoidal
      patients (P = 0.181).Modified orbital index, OA, and EB measurements are useful
      in the diagnosis of suture fusion patterns in UCS patients. Frontoparietal
      synostosis has more severe Harlequin deformity compared with frontoparietal +
      frontosphenoidal patients. Frontosphenoidal fusion coinciding with frontoparietal
      synostosis may blunt the severity of skeletal dysmorphology in UCS patients and
      be associated with a delayed diagnosis. Attention must be paid to assessing the
      frontosphenoidal suture to assure adequate surgical release.

PMID- 23147333
TI  - Bifocal mandibular fractures:  which should be treated first?
AB  - Fractures of the mandible have been reported to account between 40% and 62% of
      all facial fractures. Most surveys show that just under 50% are isolated, the
      same amount are doubly fractured. This study aims to clarify, according to our
      experience, the correct surgical sequence which should be followed in order to
      treat bifocal mandibular fractures. From January 2004 to January 2009, we have
      conducted a retrospective study on a sample of patients operated on in our
      department because of bifocal mandibular fractures. We include only those cases
      in which the jaw was fractured in 2 places, in particular patients who suffer a
      fracture in tooth-bearing areas (symphysis, parasymphysis, and anterior body) and
      also contralaterally in non-tooth-bearing areas (posterior body, angle, ramus,
      and condyle). The sample was divided into 2 groups based on the fracture sequence
      of reduction. At 1-year follow-up, the group of patients who received first the
      tooth-bearing fractured areas treatment, followed by treatment of non-tooth
      bearing fractured area on bifocal mandibular fracture, showed less postoperative
      complications and reduced surgical time and costs. It is recommended from this
      study that reduction of the tooth-bearing fragment be prior to that of the tooth
      free fragment for the bifocal mandible.

PMID- 23147334
TI  - Le Fort I osteotomy under navigational guidance for posterior repositioning of
      the maxilla.
AB  - Because navigational guidance can localize the operative site 3-dimensionally
      during maxillofacial surgery and provide precision, reliability, and safety for
      surgeons, we report Le Fort I osteotomy under navigational guidance for posterior
      repositioning of the maxilla.

PMID- 23147335
TI  - 18-gauge needle cap as adjunct to prevent kinking of endotracheal tube.
AB  - A self-retaining Dingman mouth retractor is widely used to keep the mouth open
      during cleft palate and intraoral surgery. The airway is at risk of being crushed
      or occluded as the gag (tongue plate) of the Dingman mouth retractor is being
      pushed against the endotracheal tube.Kinking of the endotracheal tube between the
      teeth and Dingman mouth retractor has been reported even with the oral Ring-Adair
      Elwyn or flexometallic or armored endotracheal tubes. To minimize kinking of the
      endotracheal tube and its consequent complications, we routinely insert an 18
      gauge needle cap at the potential space between the teeth and the tongue plate
      (gag) of the Dingman mouth retractor, which is situated lateral to the
      endotracheal tube. In our experience of approximately 5000 intraoral cases using
      a Dingman mouth retractor and 18-gauge needle cap, we have not had any tooth
      avulsion or aspiration of the 18-gauge foreign body while maintaining a
      consistent and secured airway during cleft palate and intraoral surgery.

PMID- 23147336
TI  - Autologous bone marrow-derived mononuclear cells combined with beta-TCP for
      maxillary bone augmentation in implantation procedures.
AB  - Replacing missing bone or adding mass to existing bone is often essential to the
      success of a dental implant. A large variety of graft materials have been used
      for maxillary and mandibular atrophy. To date, there has been no graft material
      which can be regarded as completely satisfactory. Our experience with freshly
      isolated autologous bone marrow-derived mononuclear cells combined with beta
      tricalcium phosphate for augmentation of the extremely atrophied maxilla is
      presented. The techniques are based on stimulation of natural events continuously
      present in living bone, that is, the process of bone remodeling. The property of
      the mixture material for bone augmentation to place dental implant was discussed.

PMID- 23147337
TI  - Interstitial pneumonitis after betadine aspiration.
AB  - Disinfection of the face and mucosa lined surfaces of the nose and mouth using a
      povidone-iodine (PI) or Betadine solution is common practice among head and neck
      surgeons. Povidone-iodine, which is a highly effective broad-spectrum antibiotic
      effective against bacteria, viruses, fungi, and protozoa, decreases the risk of
      postoperative surgical wound infection. We report a case of PI aspiration causing
      an acute chemical pneumonitis after preoperative disinfection of the oral cavity
      and nasopharynx in preparation for cleft palate repair. As a result of the
      inflammatory response, the patient required positive pressure mechanical
      ventilation and a prolonged stay in the pediatric intensive care unit. The
      patient was safely extubated on hospital day 7 and discharged on hospital day 10
      without any long-term sequelae on follow-up. We also review the 3 other reported
      cases of PI aspiration pneumonitis. Based on our case report and literature
      review, we conclude that PI aspiration is associated with a high rate of
      morbidity; however, this should not preclude the use of PI before surgery, given
      its effectiveness as an oral disinfectant and the exceedingly low incidence of
      aspiration.

PMID- 23147338
TI  - Application of piezoelectric device in endoscopic sinus surgery.
AB  - New applications of piezoelectric device have been already documented from
      otologic and ophthalmic endoscopic studies. The authors describe a first
      experience in endoscopic sinus surgery with piezosurgery to approach the
      paranasal sinus. Patients involved in this study presented for rhinogenous
      headache, rhinorrhea, nasal obstruction, and sinusitis. Radiological studies such
      as computed tomography of paranasal sinus and a correct clinical examination with
      a rigid endoscope 0 degrees were carried out, to exclude from the procedure
      patients with polyposis or other soft-tissue diseases. In fact, because of
      piezosurgery properties of micrometric and selected cutting on mineralized
      tissues, it has been used only to treat bone or cartilage anomalies of nasal
      sinus. The main advantages of the technique include soft-tissue protection and
      optimal visibility in the surgical field with decreased blood loss. From this
      preliminary report, the stability of mucous membrane previously cut has been
      documented by endoscopic follow-up, and the resolution of the main symptom of
      headache was referred. The main indications for piezosurgery shown in literature
      are in oral surgery, such as sinus lift, bone graft harvesting, osteogenic
      distraction, ridge expansion, endodontic surgery, and periodontal surgery. Other
      applications have been shown in otology, neurosurgery, ophthalmology, and
      orthopedics. Authors describe as a promising technique the piezoelectric device
      use in functional endoscopic paranasal sinus surgery in selected cases, with a
      minimal mucosal approach and thus the preservation of ventilation.

PMID- 23147339
TI  - Musculo-nasomucosal unit with complete lateral bony freeing and medial rotation
      for ideal C-shape restoration and retropositioning of the levator veli palatini.
AB  - No definitive procedure for cleft repair has been identified yet as the gold
      standard. Accordingly, this work tried to appraise the hypothesis that if the
      bony detachment and full retropositioning of the levator veli palatini muscle can
      ideally present an anatomical C-shape muscular sling restoration and if this is
      accompanied with pushback palatoplasty, would this present a better result in
      terms of tissue fistulation and phonetic impairment? A series of 74 different
      degrees of palatal clefts were operated by pushback palatoplasty combined with a
      modified approach of the levator vili palatini. This muscle was dissected only
      from the oral mucosa while kept attached to the nasal one as a musculo
      nasomucosal unit. This unit was completely detached from the bony margin of the
      hard palate and then medially rotated and retropositioned in a typical C-shape
      mobile sling. Evaluations included suture line assessment and fistula
      development, and following the child's need for speech therapy. There were no
      intraoperative complications. Definite anterior fistulae with nasal air and foot
      leakage were observed in 2 cases. Four cases had postoperative velopharyngeal
      incompetence with a need for speech therapy. Tension-free closure, lower risk of
      fistula, good restoration of velopharyngeal functions, ability to be performed on
      all cleft types, ability to provide a good intraoperative exposure, and being a
      single stage seem to be the most important advantages of this unpublished
      technique.

PMID- 23147340
TI  - Craniofacial landmarks in young children:  how reliable are measurements based on
      3-dimensional imaging?
AB  - INTRODUCTION: Different approaches for 3-dimensional (3D) data acquisition of the
      facial surface are common nowadays. Meticulous evaluation has proven their level
      of precision and accuracy. However, the question remains as to which level of
      craniofacial landmarks, especially in young children, are reliable if identified
      in 3D images. Potential sources of error, aside from the systems technology
      itself, need to be identified and addressed. Reliable and unreliable landmarks
      have to be identified. MATERIALS AND METHODS: The 3dMDface System was used in a
      clinical setting to evaluate the intraobserver repeatability of 27 craniofacial
      landmarks in 7 young children between 6 and 18 months of age with a total of 1134
      measurements. RESULTS: The handling of the system was mostly unproblematic. The
      mean 3D repeatability error was 0.82 mm, with a range of 0.26 mm to 2.40 mm,
      depending on the landmark. Single landmarks that have been shown to be relatively
      imprecise in 3D analysis could still provide highly accurate data if only 1 of
      the 3 spatial planes was relevant. There were no statistical differences from 1
      patient to another. CONCLUSIONS: Reliability in craniofacial measurements can be
      achieved by such 3D soft-tissue imaging techniques as the 3dMDface System, but
      one must always be aware that the degree of precision is strictly dependent on
      the landmark and axis in question.For further clinical investigations, the degree
      of reliability for each landmark evaluated must be addressed and taken into
      account.

PMID- 23147341
TI  - Selecting reconstruction option for TMJ ankylosis: a surgeon's dilemma.
AB  - OBJECTIVES: The aim of this study was to compare the outcome of reconstruction
      options adopted for the management of temporomandibular joint (TMJ) ankylosis.
      PATIENTS AND METHODS: This retrospective cohort study consisted of a sample of
      patients with TMJ ankylosis diagnosed clinically and radiologically. Depending
      upon the reconstruction provided, the cases were divided into 2 groups. Group I
      includes the cases treated by excision of ankylosed mass and interposition of
      temporalis myofascial flap. In group II, the cases were treated by excision,
      temporalis myofascial flap interposition, and reconstruction of ramus condylar
      unit (RCU). Two different methods of reconstruction were used, costochondral
      graft (CCG) (group IIa) and distraction osteogenesis (group IIb). The outcome
      variables were range of jaw motion, overgrowth of CCG, reankylosis, and other
      complications. Data analyses included appropriate univariate and bivariate
      statistics. RESULTS: The average mouth opening achieved in both groups was 36 mm.
      Failure was observed in 3 patients, 1 from group I and 2 from group IIa. One case
      of bilateral ankylosis and 2 cases of unilateral ankylosis had recurrence. No
      overgrowth of CCG was observed. CONCLUSIONS: In cases with no or minimal
      mandibular deformity, interpositional arthroplasty with temporalis myofascial
      flap is a good option without a second surgical wound. However, in younger
      patients, joint reconstruction with both costochondral graft and distraction
      osteogenesis of RCU is more appropriate and had similar results. The failure of
      treatment was due to noncompliance to postsurgical physiotherapy rather than the
      selection of reconstruction options.

PMID- 23147342
TI  - Porous polyethylene combined with split calvarial bone graft to cover complex
      calvarial defect.
AB  - BACKGROUND: Various kinds of grafts, such as autogenous bone grafts and
      alloplastic materials, can be used for the reconstruction of calvarial defects.
      The selection of the optimum material for the repair of cranial defects is the
      greatest problem in the reconstruction of calvarial defects. For some complex
      calvarial defects, simple use of autogenous bone grafts or alloplastic materials
      makes functional and cosmetic reconstruction difficult to achieve. Therefore, the
      current study uses a new method to repair complex calvarial defects. METHODS:
      Eight patients with complex calvarial defects underwent cranioplasty with porous
      polyethylene combined with split calvarial bone graft. Follow-up visits were
      conducted for 6 to 72 months to monitor the patients. RESULTS: Significant
      improvements in the contour of the skulls as well as in the aesthetic appearance
      of all the patients were observed. Moreover, no serious complications, such as
      infections, exposure, removal of the implants, and contour or implant
      abnormalities, were observed. Three cases displayed a transient extradural seroma
      collection, which was resolved through drainage and compression bandaging.
      CONCLUSIONS: The results of this pilot study indicate that the combined use of
      porous polyethylene and split calvarial bone graft may be useful for cranial
      reconstruction in patients with complex cranial defects.

PMID- 23147343
TI  - Piezosurgery versus conventional surgery in radicular cyst enucleation.
AB  - OBJECTIVE: This study compared the use of piezosurgery and conventional surgery
      in radicular cyst enucleation. STUDY DESIGN: The study was conducted with 29
      patients who were radiologically and cytologically prediagnosed with radicular
      cysts in the jaw region. Nineteen patients were treated using piezosurgery, and
      10 were treated using conventional surgical procedures. Surgical procedures were
      evaluated according to the following criteria: hemorrhage, soft-tissue damage,
      manipulation complexity, major perforation areas on the enucleated cyst tissue,
      and approximate operation duration. Patients were monitored postoperatively and
      evaluated for hemorrhaging at 24, 48, and 72 hours following surgery. Follow-up
      was conducted to check for recurrences and ranged from 5 to 24 months. RESULTS:
      No complications were observed in any of the 20 patients treated using
      piezosurgery, although the duration of surgery was longer than expected. Of the
      10 patients treated using conventional methods, hemorrhaging that affected the
      operation occurred in 3 cases, perforation of the cyst epithelium and
      difficulties in enucleation occurred in 5 cases, postoperative hemorrhage
      occurred in 2 cases, and recurrence was observed in 2 cases. CONCLUSIONS:
      Piezosurgery may be considered effective in procedures such as enucleation that
      require sensitive manipulation, despite the increase in the length of the overall
      surgical procedure. Given the results of the present study and the current lack
      of information in the literature regarding postoperative pain, infection, and
      long-term success rates associated with the use of piezosurgery in cyst
      enucleation, further study in this area is recommended.

PMID- 23147344
TI  - Periodontal manifestations and ambulatorial management in a patient with Sturge
      Weber syndrome.
AB  - Sturge-Weber syndrome is a nonhereditary congenital condition characterized by
      leptomeningeal and facial skin angiomatous malformation following the trigeminal
      nerve path. The intraoral angiomatosis are presented in 40% of cases and results
      in an important periodontal alteration, increasing the risk of bleeding during
      dental procedures. A 43-year-old male patient presented with port wine stain on
      the right side of the face, the entire hard and soft palates, the alveolar ridge,
      and buccal mucosa, and had an excessive accumulation of calcified masses in both
      supragingival and subgingival sites, with swelling and generalized inflammation
      throughout the gingiva and alveolar mucosa. He reported not having sanitized the
      area for years for fear of bleeding. Periodontal management, to remove calculus
      and to control gingivitis initiated in the supragingival region and gradually
      reaching the subgingival region to control oral microbiota, was performed with
      mild bleeding. The redness of the staining greatly diminished with time and the
      extreme halitosis of the patient also improved sharply leading to a dramatic
      improvement in quality of life. Ambulatory care is a feasible alternative for
      periodontal management that within safety limits for bleeding risks reduces the
      operational cost.

PMID- 23147345
TI  - Paralysis of cranial nerve and striking prognosis of cervical necrotizing
      fasciitis.
AB  - Necrotizing soft-tissue infection (NSTI) is a bacterial infection with necrosis
      of the cutaneous, subcutaneous tissue and fascia with sparing of the underlying
      muscle. The most frequent initiating factor reported, for necrotizing fasciitis,
      in the head and neck region is a primary odontogenic infection or postextraction
      infection, abrasion, and laceration of the face or scalp. Necrotizing fasciitis
      can progress rapidly to systemic toxicity and even death if not promptly
      diagnosed and treated. If the patient has any risk factors, this can worsen the
      prognosis. In this study, 2 cases of NSTI with dental pathology history (one with
      the spreading to mediastinum and the other spreading to suprahyoid) were
      discussed with a review of the literature. One of the cases had diabetes
      mellitus, but interestingly, she had a better prognosis, and she was discharged
      asymptomatic. In addition, the other case had no any risk factors, but he had a
      worse clinical cranial nerve paralysis (a rare complication of NSTI) and died. As
      a conclusion, despite the intensive therapy, large debridement, and antibiotics
      with large spectrum, the delay in the patient's diagnosis and treatment increased
      mortality. We aimed to attract attention to the importance of dental pathologies
      and early diagnosis.

PMID- 23147346
TI  - Clinical comparison between the retromandibular approach for reduction and
      fixation and endoscope-assisted open reduction and internal fixation for
      mandibular condyle fractures.
AB  - OBJECTIVE: Endoscope-assisted transoral open reduction and internal fixation
      (EAORIF) for mandibular condyle fractures has recently become popular because it
      is minimally invasive, provides excellent visibility without a large incision,
      and reduces surgical scarring and the risk of facial nerve injury. This report
      describes a retrospective clinical study that compared certain clinical
      parameters, including postoperative function, between the retromandibular (RM)
      approach and EAORIF. METHODS: Fifteen patients were treated by the RM approach,
      whereas 15 underwent EAORIF between July 2006 and September 2011 at Kyushu Dental
      College, Japan. Clinical indices comprised fracture line, fracture type, number
      of plates used, surgical duration, bleeding amount, and functional items,
      including maximum interincisal opening, mandibular deviation on the opening
      pathway, malocclusion, facial paresthesia, and temporomandibular joint pain and
      clicking. RESULTS: The areas subjected to either approach included lower neck and
      subcondyle. The RM approach was used for mandibular condyle fractures with
      dislocation of a small bone segment. Both groups used 2 plates in all cases.
      Surgical duration, maximum interincisal opening, mandibular deviation, occlusion,
      and temporomandibular joint function at 6 months after surgery were comparable
      between groups. The average bleeding amount in the EAORIF group was greater than
      in the RM group. One patient from the RM group developed facial paresthesia that
      persisted for 6 months after surgery. CONCLUSIONS: It was concluded that surgical
      treatment was suitable for fractures of the lower neck and subcondylar. Both
      procedures showed good results in the functional items of this study.

PMID- 23147347
TI  - Endoscopy-assisted cerebral falx incision via unilateral approach in treatment of
      dissymmetric bilateral frontal contusion.
AB  - BACKGROUND: Dissymmetric bilateral frontal contusion (DBFC) is relatively
      frequent in the clinic. In this study, we aimed to investigate the development
      tendency, clinical features, and treatment experience of DBFC and to summarize
      out experience in treating these patients via minimally invasive means-endoscopy.
      METHODS: Over the past 3 years, we have treated a total of 31 patients with DBFC
      using endoscopy-assisted unilateral cerebral falx incision. We used a 30-degree
      endoscope to observe the involvement of brain contusion and whether the brain
      contusions have been cleaned thoroughly. Another 30 patients treated by routine
      bilateral approach within the same period were taken as controls. RESULTS:
      Seventeen cases (54.8%) in the unilateral-operation group survived and were in
      good condition, 8 cases (25.8%) had moderate disability, and 4 cases (12.9%) had
      severe disability; 1 case (3.2%) was in vegetable state, and 1 case (3.2%) died.
      Compared with the control group, the GOS score was not significantly different in
      the unilateral-operation group, but the operation time, blood transfusion volume,
      length of hospital stay, incidence of mental disorder, and incidence of olfactory
      nerve injury were greatly reduced in the unilateral-operation group. CONCLUSIONS:
      Endoscopy-assisted unilateral cerebral falx incision can shorten the operation
      time and reduce surgical trauma and complications when used for treatment of
      patients with DBFC.

PMID- 23147348
TI  - Delayed carotid pseudoaneurysm:  a life-threatening complication after endoscopic
      sinus surgery.
AB  - Internal carotid artery pseudoaneurysm is a rare but potentially lethal
      complication of sinus surgery. We present 2 cases of delayed carotid
      pseudoaneurysm development after internal carotid laceration during functional
      sinus surgery for chronic sinusitis to emphasize the need to follow up the
      patients with profuse bleeding perioperatively and to identify when to suspect
      iatrogenic vascular malformations.

PMID- 23147349
TI  - Temporomandibular disorders in scuba divers-an increased risk during diving
      certification training.
AB  - The design of a diving regulator's mouthpiece increases the risk of a
      temporomandibular disorder (TMD) in scuba divers. The total weight of a diving
      regulator is reflected directly on the temporomandibular joint, causing articular
      and periarticular disorders. In the current study, the prevalence of TMD in scuba
      divers triggered during diving certification training is investigated. We also
      aimed to determine the factors that lead to TMD during diving training and
      clarify the observation that there is an increased incidence of TMD in
      inexperienced divers. The study was held between 2006 and 2011. Ninety-seven
      divers were referred with the complaint of pain around temporomandibular area.
      The divers were classified according to their diving experience. Symptoms and
      signs of TMD were graded. Fourteen divers were diagnosed with TMD.
      Temporomandibular disorder was seen more frequently in inexperienced divers than
      in experienced divers (P = 0.0434). The most prevalent symptom was an increased
      effort for mouthpiece gripping. Temporomandibular joint tenderness and trigger
      point activation were the mostly seen physical signs. Thirteen divers had an
      improvement with therapy. The increased effort for stabilizing the mouthpiece is
      a recognized factor in TMD development. Attention must be paid to an association
      of scuba diving with TMDs, especially in inexperienced divers having a scuba
      certification training.

PMID- 23147351
TI  - Immunohistochemical study of another case of lipoatrophic panniculitis of the
      ankles in childhood.

PMID- 23147350
TI  - Differential expression of the G-protein-coupled formyl Peptide receptor in
      melanoma associates with aggressive phenotype.
AB  - Melanoma, due to its metastatic rate, is among the most aggressive forms of skin
      cancer. Human formyl peptide receptor (FPR) and its variant FPR-like 1 (FPRL1)
      have been associated with cell migration and invasiveness in neoplasms. We have
      studied the in situ expression of these receptors in a large series of
      melanocytic lesions and correlated the expression with clinicopathological
      features and prognosis. Tissue microarray blocks of 141 cases including nevi (31
      cases), primary (84 cases), and metastatic melanomas (26 cases) were
      semiquantitatively evaluated by immunohistochemistry for the expression of FPR
      and FPRL1 proteins. A significant association was observed regarding diagnosis
      and percentage of cells showing expression of FPR (P = 0.0311) and FPRL1 (P =
      0.0053). A gain of FPR immunoreactivity was observed in the lesions having
      ulceration (P = 0.0194) and Breslow thickness (P = 0.044). Also, high FPRL1
      cytoplasmic immunoreactivity was seen in lesions without tumor regression (P =
      0.04). In addition, in patients with increased cytoplasmic staining for FPR, the
      probability of disease-specific survival was significantly lower (log rank test,
      P = 0.0089). Our findings reveal that FPR and FPRL1 are overexpressed in primary
      melanoma and correlate with aggressive tumor characteristics, underscoring them
      as potential therapeutic targets.

PMID- 23147352
TI  - Acrodermatitis chronica atrophicans with pseudolymphomatous infiltrates.
AB  - In this study, we describe the clinicopathologic features of pseudolymphomatous
      infiltrates found within lesions of acrodermatitis chronica atrophicans (ACA). We
      studied 11 patients (10 females, 1 male, age range 60-88 years). The diagnosis of
      ACA in all cases was confirmed by clinicopathologic correlation and positive
      serology for Borrelia. Histopathologic examination revealed prominent,
      pseudolymphomatous inflammatory cell infiltrates in all cases, with 2 distinct
      patterns. Eight of 11 cases showed a band-like lymphocytic infiltrate, exocytosis
      of lymphocytes and a fibrotic papillary dermis, similar to features seen in
      mycosis fungoides. The other 3 cases showed dense, nodular-diffuse dermal
      infiltrates with many plasma cells and without germinal centers. The plasma cells
      expressed both kappa and lambda immunoglobulin light chains with a polyclonal
      pattern in all 3 cases. In conclusion, ACA may present with pseudolymphomatous
      infiltrates showing both a T-cell and, less frequently, a B-cell pattern. These
      lesions need to be distinguished from a cutaneous lymphoma. In the context of the
      knowledge of Borrelia-associated cutaneous lymphomas, follow-up seems advisable
      in these cases.

PMID- 23147353
TI  - Case of metastatic basal cell carcinoma to bone marrow, resulting in
      myelophthisic anemia.
AB  - BACKGROUND: While basal cell carcinoma (BCC) remains the most common skin cancer,
      the incidence of metastasis is rare. Most cases of metastatic BCC have been to
      regional lymph nodes. Metastasis to bone marrow with myelophthisic anemia is
      especially rare. To our knowledge, there have been only 5 reported cases in
      literature. We report a sixth case. OBSERVATIONS: A 46-year-old male patient
      presented with an 8 * 7-cm ulcerated plaque on his chest, found to be morpheaform
      basal cell on pathology. Laboratory findings were notable for normocytic anemia,
      thrombocytopenia, and elevated LDH. Further work up with bone marrow biopsy
      revealed tumor cells staining positive for CK AE1/AE3, BerEP4, CK7, CD56, and PIN
      4. This confirmed the diagnosis of metastatic BCC (MBCC) to bone marrow.
      CONCLUSIONS: Although the rate of metastasis for BCC is rare, once it occurs,
      prognosis is poor. MBCC remains a challenge to treat. Therefore, it is critical
      to resolve the primary BCC and obtain vigilant follow-up, especially in patients
      with multiple risk factors for MBCC.

PMID- 23147354
TI  - Prognostic impact of the Charlson comorbidity index on mortality following acute
      pulmonary embolism.
AB  - OBJECTIVES: It was the aim of this study to determine the prognostic significance
      of the Charlson Comorbidity Index (CCI) following acute pulmonary embolism (PE)
      and assess the prognosis of patients without comorbidities (defined as a CCI
      score of 0). METHODS: Outcomes of 1,023 consecutive patients admitted with
      confirmed PE were tracked after a median of 3.7 years (25-75th interquartile
      range 1.5-6.1 years). All were assigned a non-age-adjusted CCI score. RESULTS:
      The median CCI score was 1.0 (interquartile range 0.0-3.0). Three hundred and
      fifty-one (34%) patients had a CCI score of 0. Only 1 (0.3%) of 31 in-hospital
      deaths occurred in patients with a CCI score of 0. Long-term mortality for these
      patients was similar to the population-derived age- and sex-matched mortality
      rate, and was significantly better than for those with a CCI score >=1 (12.5 vs.
      47.5%; p < 0.0001 adjusted for age and sex). In multivariate analysis, CCI (per 1
      score increase) independently predicted in-hospital (hazard ratio 1.27, 95%
      confidence interval 1.09-1.49; p = 0.003) and post-discharge (hazard ratio 1.35,
      95% confidence interval 1.29-1.42; p < 0.0001) death. The c statistics for the
      multivariate prediction models for in-hospital (incorporating CCI score and serum
      sodium level) and post-discharge death (age, CCI score, hyperlipidemia, serum
      sodium and hemoglobin) were 0.738 and 0.788, respectively (both p < 0.0001).
      CONCLUSION: The CCI can be incorporated into risk models, with good
      discriminatory power, for predicting in-hospital and long-term outcomes following
      acute PE. Patients with a CCI score of 0 have a favorable long-term outcome
      following acute PE.

PMID- 23147355
TI  - beta-Cobalt sulfide nanoparticles decorated graphene composite electrodes for
      high capacity and power supercapacitors.
AB  - Electrochemical supercapacitors have drawn much attention because of their high
      power and reasonably high energy densities. However, their performances still do
      not reach the demand of energy storage. In this paper beta-cobalt sulfide
      nanoparticles were homogeneously distributed on a highly conductive graphene (CS
      G) nanocomposite, which was confirmed by transmission electron microscopy
      analysis, and exhibit excellent electrochemical performances including extremely
      high values of specific capacitance (~1535 F g(-1)) at a current density of 2 A
      g(-1), high-power density (11.98 kW kg(-1)) at a discharge current density of 40
      A g(-1) and excellent cyclic stability. The excellent electrochemical
      performances could be attributed to the graphene nanosheets (GNSs) which could
      maintain the mechanical integrity. Also the CS-G nanocomposite electrodes have
      high electrical conductivity. These results indicate that high electronic
      conductivity of graphene nanocomposite materials is crucial to achieving high
      power and energy density for supercapacitors.

PMID- 23147356
TI  - UCL Partnership NHS Staff College.

PMID- 23147357
TI  - Investigating iron deficiency in the severely obese: challenges and solutions.

PMID- 23147359
TI  - The role of thoracic imaging in the intensive care unit.
AB  - Radiology is critical in managing patients on intensive care units. The portable
      chest X-ray is widely used, but ultrasound and computed tomography are of
      diagnostic value in selected cases. This article discusses the role of thoracic
      imaging in the intensive care unit.

PMID- 23147360
TI  - Imaging incidental pulmonary nodules.
AB  - The incidental nodule is an increasingly common clinical conundrum. This article
      outlines  the characteristics that allow differentiation of benign and malignant
      pathologies and  discusses strategies for their follow up and management.

PMID- 23147361
TI  - Imaging the pleura.
AB  - Pleural disease is now recognized as an important subspecialty of pulmonary
      medicine, with increasing provision being made for specialist services and
      procedures. In response, the field of pleural imaging has advanced in recent
      years, especially with regard to ultrasound. Salient multimodality imaging
      techniques are discussed.

PMID- 23147362
TI  - Surgical management of  end-stage heart failure.
AB  - This review explores the history, methods and evidence surrounding the various
      surgical therapeutic options which are available for patients with end-stage
      heart failure.

PMID- 23147363
TI  - Supportive and palliative care for people with end-stage renal disease.
AB  - Advanced renal failure has a mortality rate worse than for most cancers with
      significant symptom burden. Despite this palliative care for this group has been
      poor. This article summarizes the role that palliative and nephrology teams can
      play in optimizing end-of-life care.

PMID- 23147364
TI  - Protocol-guided hip fracture management  reduces length of hospital stay.
AB  - OBJECTIVE: To see if protocolised hip fracture care led to an improvement in
      patient management and more standardized treatment with the aim of reducing wait
      for surgery and postoperative length of stay. DESIGN: Following the introduction
      and establishment of a care pathway a retrospective, observational audit was
      conducted with patient data and pathway compliance obtained from analysing
      medical notes and accessing electronic patients' records. SETTING: The audit
      analysed all patients who sustained a fractured hip admitted to University
      College London Hospital over 18-month period between August 2009 and February
      2011. MEASUREMENTS: In addition to demographic data, a comparison was made
      between those who were and were not managed with the care pathway. Investigation,
      preoperative management, time to surgery, length of stay and mortality were all
      evaluated. RESULTS: Patients managed via the care pathway had significantly more
      investigations and preoperative interventions, had subsequently had a reduced
      length of hospital stay (a mean average of 13 compared to 17 days). There was no
      significant difference in time from admission to surgery, and 30-day mortality.
      CONCLUSIONS: Using a care pathway to manage those patients sustaining fractured
      femur appears to make preoperative management more consistent. This, in turn,
      leads to a reduction in length of hospital stay.

PMID- 23147365
TI  - Sir Benjamin Collins Brodie: a distinguished surgeon.

PMID- 23147366
TI  - Accidental overdose of proprietary branded, combination analgesics available over
      the counter.

PMID- 23147367
TI  - Lemierre's syndrome masquerading  as necrotizing fasciitis.

PMID- 23147368
TI  - Bridging the communication gap between health-care providers and patients'
      advocates.

PMID- 23147370
TI  - Fresh frozen plasma for correction of the international normalized ratio: safe
      practice?

PMID- 23147371
TI  - Multidimensional OH local mode calculations for OH(-)(H2O)3--importance of
      intermode anharmonicity.
AB  - We present theoretical calculations on the vibrational spectra between the energy
      range of 2000-4000 cm(-1) for 4 isoenergetic conformers of gas phase OH(
      )(H(2)O)(3) and OH(-)(H(2)O)(3).Ar clusters. The peak positions and associated
      intensities of the OH stretching vibrations were calculated using an extended
      local mode model on multi-dimensional ab initio potential energy surfaces and
      dipole moment functions obtained by MP2/6-311++G(3df,3pd). Furthermore, to
      simulate the experimental spectra directly, both the homogeneous and
      inhomogeneous line widths were determined theoretically. For the ionic hydrogen
      bonded OHs, which directly bind to the OH(-), anharmonic coupling between the OHs
      on different water units is crucial for the reproduction of experimentally
      observed features. On the other hand, the coupling between free OH stretching
      vibrations is so small that the usual 1-dimensional local mode model provides a
      good and economical way to obtain the spectra. By comparing the theoretical
      spectra for 4 isoenergetic conformers, we found that the ionic hydrogen bonded OH
      stretching peaks can act as a descriptor for the subtle conformational
      differences in the first solvation shell. Furthermore, we showed that the
      coupling between the ionic hydrogen bonded OH and low frequency OO stretching
      vibrations can cause fairly strong combination bands, and that the weakly bound
      argon, which was used as a messenger in the experiment by Robertson et al.
      [Science; 2003, 299, 1367], causes shifts on the peak positions for the ionic
      hydrogen bonded OHs. In addition, we quantified the effect of counterpoise
      correction on the simulated spectra for the ionic hydrogen bonded OHs.

PMID- 23147372
TI  - Testicular fusion in a patient with crossed testicular ectopia: a rare entity.
AB  - Crossed testicular ectopia (CTE) is a well-described, rare congenital abnormality
      of testicular descent, in which both testes migrate through one inguinal canal.
      The objective of this work is to present a case of fused two testicles in a
      hemiscrotum as a rare entity of CTE. We describe a rare case of CTE in a 19-year
      old boy presenting to the Department with left testis placed in the right
      hemiscrotum with right inguinal hernia. Ultrasound and magnetic resonance imaging
      revealed fused testes with their own vasa deferentia in the left hemiscrotum.
      Azoospermia was detected in semen analysis. The patient was referred to microTESE
      and ICSI procedure for his infertility problem. CTE should be kept in mind in
      patients with an inguinal hernia and contralateral nonpalpable testis.

PMID- 23147373
TI  - Flexible bivariate phase II clinical trial design incorporating toxicity and
      response on different schedules.
AB  - The single-arm, two-stage clinical trial is a popular design utilized to evaluate
      oncology treatments. The designs are typically augmented with an ad hoc toxicity
      monitoring rule that is imposed outside of the formal two-stage design. In this
      work, we present a flexible bivariate single-arm clinical trial design that
      incorporates both response and toxicity. The design is considered flexible
      because it can monitor toxicity on a different schedule from the response. An
      example is considered in which toxicity is measured at four equally spaced times,
      which correspond to the data monitoring committee's meeting schedule while
      evaluating the response only at the second and fourth toxicity evaluations. The
      effect of the correlation on the types I and II error rates is examined through
      simulation. The simulations also examine the power over the response rates when
      the toxicity rate is fixed in the alternative region and vice versa.

PMID- 23147374
TI  - Relationship between chemokine receptor expression, chemokine levels and HIV-1
      replication in the lungs of persons exposed to Mycobacterium tuberculosis.
AB  - Increased susceptibility to tuberculosis following HIV-1 seroconversion
      contributes significantly to the tuberculosis epidemic in sub-Saharan Africa.
      Lung-specific mechanisms underlying the interaction between HIV-1 and
      Mycobacterium tuberculosis infection are incompletely understood. Here we address
      these questions by examining the effect of HIV-1 and latent M. tuberculosis co
      infection on the expression of viral-entry receptors and ligands in
      bronchoalveolar lavage (BAL) of HIV-1-infected and -uninfected patients with and
      without latent M. tuberculosis infection. Irrespective of HIV-1 status, T cells
      from BAL expressed higher levels of the beta-chemokine receptor (CCR)5 than
      peripheral blood T cells, in particular the CD8(+)  T cells of HIV-1-infected
      persons showed elevated CCR5 expression. The concentrations of the CCR5 ligands
      RANTES and MIP-1beta were elevated in the BAL of HIV-1-infected persons compared
      with that in HIV-1-uninfected controls. CCR5 expression and RANTES concentration
      correlated strongly with HIV-1 viral load in the BAL. In contrast, these
      alterations were not associated with M. tuberculosis sensitisation in vivo, nor
      did M. tuberculosis infection of BAL cells ex vivo change RANTES expression.
      These data suggest ongoing HIV-1 replication predominantly drives local pulmonary
      CCR5(+)  T-cell activation in HIV/latent M. tuberculosis co-infection.

PMID- 23147376
TI  - Influence of experimental type 1 diabetes on the pulmonary effects of diesel
      exhaust particles in mice.
AB  - Epidemiologically, exposure to particulate air pollution is associated with
      increases in morbidity and mortality, and diabetics are especially vulnerable to
      effects of particles. This study was carried out to determine the respiratory
      effect of diesel exhaust particles (DEP; 0.4mg/kg) on mice rendered diabetic by
      the injection of streptozotocin or vehicle (control). Four weeks following
      induction of diabetes, the animals were intratracheally instilled (i.t.) with DEP
      (0.4mg/kg) or saline. 24h later, the measurement of airway reactivity to
      methacholine in vivo by a forced oscillation technique showed a significant and
      dose-dependent increase in airway resistance in non-diabetic mice exposed to DEP
      versus non-diabetic mice exposed to saline. Similarly, the airway resistance was
      significantly increased in diabetic mice exposed to DEP versus diabetic mice
      exposed to saline. Nevertheless, there was no difference in the airway resistance
      between diabetic and non-diabetic mice after i.t. administration of DEP.
      Following DEP administration there were neutrophil polymorphs infiltration of
      pulmonary interalveolar septae and the alveolar spaces with many macrophages
      containing DEP in both diabetic and non-diabetic mice. Interestingly, apoptotic
      cells were only found in the examined lung sections from diabetic mice exposed to
      DEP. Total proteins and albumin concentrations in bronchoalveolar lavage (BAL)
      fluid, markers for increase of epithelial permeability, were significantly
      increased in diabetic mice exposed to DEP compared to saline-treated diabetic and
      DEP-treated non diabetic mice. Superoxide dismutase activity and reduced
      glutathione concentration in BAL were significantly decreased in diabetic mice
      exposed to DEP compared to saline-treated diabetic and DEP-treated non diabetic
      mice. Moreover, tumor necrosis factor alpha (TNFalpha) concentrations were
      significantly increased in diabetic mice exposed to DEP compared to saline
      treated diabetic and DEP-treated non diabetic mice. We conclude that, at the dose
      and time point investigated, DEP equally increased airway resistance and caused
      infiltration of inflammatory cells in the lung of both diabetic and non-diabetic
      mice. However, the occurrence of oxidative stress, the presence lung apoptotic
      cells and the increase of total proteins, albumin and TNFalpha in BAL fluid were
      only seen in DEP-exposed diabetic mice suggesting an increased respiratory
      susceptibility to particulate air pollution.

PMID- 23147375
TI  - Characteristic molecular signature for the early detection and prediction of
      polycyclic aromatic hydrocarbons in rat liver.
AB  - Predictions of toxicity are central for the assessment of chemical toxicity, and
      the effects of environmental toxic compounds are still a major issue for
      predicting potential human health risks. Among the various environmental
      toxicants, polycyclic aromatic hydrocarbons (PAHs) are an important class of
      environmental pollutant, and many PAHs are known or suspected carcinogens. In the
      present study, to investigate whether characteristic expression profiles of PAHs
      exist in rat liver and whether a characteristic molecular signature can
      discriminate and predict among different PAHs at an early exposure time, we
      analyzed the genome-wide expression profiles of rat livers exposed to PAHs
      [benzo[a]anthracene (BA), benzo[a]pyrene (BP), phenanthrene (PA) and naphthalene
      (NT)]. At early time-point PAH exposure, large-scale gene expression analysis
      resulted in characteristic molecular signatures for each PAH, and supervised
      analysis identified 1183 outlier genes as a distinct molecular signature
      discerning PAHs from the normal control group. We identified 158 outlier genes as
      early predictive and surrogate markers for predicting each tested PAH by
      combination of two different multi-classification algorithms with 100% accuracy
      through a leave-one out cross-validation method. In conclusion, the
      characteristic gene expression signatures from a rat model system could be used
      as predictable and discernible gene-based biomarkers for the detection and
      prediction of PAHs, and these molecular markers may provide insights into the
      underlying mechanisms for genotoxicity of exposure to PAHs from environmental
      aspect.

PMID- 23147377
TI  - Iron oxide particles modulate the ovalbumin-induced Th2 immune response in mice.
AB  - This study was designed to investigate the modulatory effects of submicron and
      nanosized iron oxide (Fe(2)O(3)) particles on the ovalbumin (OVA)-induced immune
      Th2 response in BALB/c mice. Particles were intratracheally administered four
      times to mice before and during the OVA sensitization period. For each particle
      type, three different doses, namely 4*100, 4*250 or 4*500 MUg/mouse, were used
      and for each dose, four groups of mice, i.e. group saline solution (1), OVA (2),
      particles (3), and OVA plus particles (4), were constituted. Mice exposed to OVA
      alone exhibited an allergic Th2-dominated response with a consistent increase in
      inflammatory scores, eosinophil numbers, specific IgE levels and IL-4 production.
      When the mice were exposed to OVA and to high and intermediate doses of iron
      oxide submicron- or nanoparticles, the OVA-induced allergic response was
      significantly inhibited, as evidenced by the decrease in eosinophil cell influx
      and specific IgE levels. However, the low dose (4*100 MUg) of submicron particles
      had no significant effect on the OVA allergic response while the same dose of
      nanoparticles had an adjuvant effect on the Th2 response to OVA. In conclusion,
      these data demonstrate that the pulmonary immune response to OVA is a sensitive
      target for intratracheally instilled particles. Depending on the particle dose
      and size, the allergic response was suppressed or enhanced.

PMID- 23147378
TI  - Ustilago species as a cause of central line-related blood stream infection.
AB  - Ustilago, commonly referred to as "corn smut," rarely causes human disease.
      Serious clinical infections caused by Ustilago species have been sparsely
      reported in medical literature. In this study, a case of central line infection
      caused by Ustilago species is presented.

PMID- 23147379
TI  - Urothelial bladder carcinoma with choriocarcinomatous differentiation presenting
      with a false-positive pregnancy test.
AB  - Urothelial carcinoma of the bladder with choriocarcinomatous features is a rare
      presentation among genitourinary cancers. In this study, the case of a 42-year
      old woman who presented with menstrual irregularity and positive urine and serum
      beta-human chorionic gonadotropin tests is presented. Pelvic ultrasound showed no
      intrauterine pregnancy. Laparoscopy and hysteroscopy with dilatation and
      curettage were negative for evidence of trophoblastic tissue. Computed tomography
      of the abdomen and pelvis showed an intravesical fundal mass, with no evidence of
      extravesical disease. Cystoscopy and transurethral resection of the bladder tumor
      diagnosed an invasive high-grade urothelial carcinoma with trophoblastic
      differentiation and multiple foci of choriocarcinomatous morphology. The patient
      received 3 cycles of neoadjuvant chemotherapy with methotrexate, vinblastine,
      adriamycin and cisplatin and then underwent partial cystectomy, which was
      negative for any residual tumor. This is the first reported case of a positive
      urine pregnancy test leading to the diagnosis of urothelial carcinoma.

PMID- 23147380
TI  - Evaluation of urinary biomarkers for the prognosis of drug-associated chronic
      tubulointerstitial nephritis.
AB  - BACKGROUND: The efficacy of urinary biomarkers for predicting adverse clinical
      outcomes in drug-induced chronic tubulointerstitial nephritis (D-CTIN) has not
      been well described. METHODS: A total of 54 patients with D-CTIN were
      prospectively followed-up in this study. The urinary excretion of alpha1
      microglobulin and transforming growth factor-beta1 and the activity of urinary N
      acetyl-beta-D-glucosaminidase (NAG) and matrix metalloproteinases (MMPs) 2 and 9
      at baseline were measured. Changes in the estimated glomerular filtration rate
      (GFR) over a period of 11 to 54 months (median, 38 months) of follow-up were
      recorded. The efficacy of urinary biomarkers for differentiating patients with
      various outcomes was tested. Ten patients with IgA nephropathy and 20 healthy
      volunteers were enrolled as controls. RESULTS: The areas under the receiver
      operating characteristic curve for urinary NAG, MMP-9, MMP-2 and alpha1
      microglobulin for predicting deterioration of the estimated GFR were 0.879,
      0.867, 0.735 and 0.709, respectively (P < 0.05 for all). Partial regression
      coefficient results demonstrated that urinary NAG (P = 0.02), MMP-2 (P = 0.046)
      and MMP-9 (P = 0.041) were inversely correlated with the rate of GFR decline.
      CONCLUSIONS: Urinary NAG, MMP-2 and MMP-9 may be considered as possible
      candidates for forecasting the progression rate of D-CTIN.

PMID- 23147381
TI  - Change in alexithymia in two dynamically informed individual psychotherapies.

PMID- 23147382
TI  - Oxytocin increases anxiety to unpredictable threat.

PMID- 23147383
TI  - Combined analysis of exome sequencing points toward a major role for
      transcription regulation during brain development in autism.

PMID- 23147387
TI  - Biodegradation of tetrahydrofuran and 1,4-dioxane by soluble diiron monooxygenase
      in Pseudonocardia sp. strain ENV478.
AB  - 1,4-Dioxane is an important groundwater contaminant. Pseudonocardia sp. strain
      ENV478 degrades 1,4-dioxane via cometabolism after the growth on tetrahydrofuran
      (THF) and other carbon sources. Here, we have identified a THF monooxygenase
      (thm) in ENV478. The thm genes are transcribed constitutively and are induced to
      higher levels by THF. Decreased translation of the thmB gene encoding one of the
      monooxygenase subunits by antisense RNA resulted in the loss of its ability to
      degrade THF and 1,4-dioxane. This is the first study to link thm genes to THF
      degradation, as well as the cometabolic oxidation of 1,4-dioxane.

PMID- 23147385
TI  - Two gene co-expression modules differentiate psychotics and controls.
AB  - Schizophrenia (SCZ) and bipolar disorder (BD) are highly heritable psychiatric
      disorders. Associated genetic and gene expression changes have been identified,
      but many have not been replicated and have unknown functions. We identified
      groups of genes whose expressions varied together, that is co-expression modules,
      then tested them for association with SCZ. Using weighted gene co-expression
      network analysis, we show that two modules were differentially expressed in
      patients versus controls. One, upregulated in cerebral cortex, was enriched with
      neuron differentiation and neuron development genes, as well as disease genome
      wide association study genetic signals; the second, altered in cerebral cortex
      and cerebellum, was enriched with genes involved in neuron protection functions.
      The findings were preserved in five expression data sets, including sets from
      three brain regions, from a different microarray platform, and from BD patients.
      From those observations, we propose neuron differentiation and development
      pathways may be involved in etiologies of both SCZ and BD, and neuron protection
      function participates in pathological process of the diseases. 

PMID- 23147384
TI  - Effects of the mu-opioid receptor antagonist GSK1521498 on hedonic and
      consummatory eating behaviour: a proof of mechanism study in binge-eating obese
      subjects.
AB  - The opioid system is implicated in the hedonic and motivational processing of
      food, and in binge eating, a behaviour strongly linked to obesity. The aim of
      this study was to evaluate the effects of 4 weeks of treatment with the mu-opioid
      receptor antagonist GSK1521498 on eating behaviour in binge-eating obese
      subjects. Adults with body mass index >= 30 kg m(-2) and binge eating scale
      scores >= 19 received 1-week single-blind placebo run-in, and were then
      randomized to 28 days with either 2 mg day(-1) GSK1521498, 5 mg day(-1)
      GSK1521498 or placebo (N=21 per arm) in a double-blind parallel group design. The
      outcome measures were body weight, fat mass, hedonic and consummatory eating
      behaviour during inpatient food challenges, safety and pharmacokinetics. The
      primary analysis was the comparison of change scores in the higher-dose treatment
      group versus placebo using analysis of covariance at each relevant time point.
      GSK1521498 (2 mg and 5 mg) was not different from placebo in its effects on
      weight, fat mass and binge eating scores. However, compared with placebo,
      GSK1521498 5 mg day(-1) caused a significant reduction in hedonic responses to
      sweetened dairy products and reduced calorific intake, particularly of high-fat
      foods during ad libitum buffet meals, with some of these effects correlating with
      systemic exposure of GSK1521498. There were no significant effects of GSK1521498
      2 mg day(-1) on eating behaviour, indicating dose dependency of pharmacodynamics.
      GSK1521498 was generally well tolerated and no previously unidentified safety
      signals were detected. The potential for these findings to translate into
      clinically significant effects in the context of binge eating and weight regain
      prevention requires further investigation.

PMID- 23147386
TI  - CRHR1 genotypes, neural circuits and the diathesis for anxiety and depression.
AB  - The corticotrophin-releasing hormone (CRH) system integrates the stress response
      and is associated with stress-related psychopathology. Previous reports have
      identified interactions between childhood trauma and sequence variation in the
      CRH receptor 1 gene (CRHR1) that increase risk for affective disorders. However,
      the underlying mechanisms that connect variation in CRHR1 to psychopathology are
      unknown. To explore potential mechanisms, we used a validated rhesus macaque
      model to investigate association between genetic variation in CRHR1, anxious
      temperament (AT) and brain metabolic activity. In young rhesus monkeys, AT is
      analogous to the childhood risk phenotype that predicts the development of human
      anxiety and depressive disorders. Regional brain metabolism was assessed with
      (18)F-labeled fluoro-2-deoxyglucose (FDG) positron emission tomography in 236
      young, normally reared macaques that were also characterized for AT. We show that
      single nucleotide polymorphisms (SNPs) affecting exon 6 of CRHR1 influence both
      AT and metabolic activity in the anterior hippocampus and amygdala, components of
      the neural circuit underlying AT. We also find evidence for association between
      SNPs in CRHR1 and metabolism in the intraparietal sulcus and precuneus. These
      translational data suggest that genetic variation in CRHR1 affects the risk for
      affective disorders by influencing the function of the neural circuit underlying
      AT and that differences in gene expression or the protein sequence involving exon
      6 may be important. These results suggest that variation in CRHR1 may influence
      brain function before any childhood adversity and may be a diathesis for the
      interaction between CRHR1 genotypes and childhood trauma reported to affect human
      psychopathology.

PMID- 23147388
TI  - Do depression and educational attainment mediate the association between
      ethnicity and dementia?
AB  - INTRODUCTION: Research shows marked differences in the prevalence of dementia
      among different ethnic groups. However, there is a relative dearth of studies
      focusing on how ethnicity may influence dementia. The main aim of the current
      study is to test potential mediating effects of depression and level of education
      on the association between ethnicity and dementia. METHODS: The sample for this
      study, consisting of 2,796 community-dwelling elderly people aged 60 years and
      older, was drawn from a cross-sectional national survey entitled 'Mental Health
      and Quality of Life of Older Malaysians'. The Malaysian adapted version of the
      Geriatric Mental State-Automated Geriatric Examination for Computer-Assisted
      Taxonomy was used to assess dementia and depression. Data analysis was conducted
      using IBM SPSS version 19. RESULTS: As expected, the result of the chi2 analysis
      revealed significant ethnic difference in the prevalence of dementia (chi2 =
      58.05, p <= 0.001). The results of the mediational analyses revealed that
      depression (Z = 4.05, p <= 0.001) and education (Z = 2.78, p <= 0.01)
      significantly, but partially, mediate the association between ethnicity and
      dementia. This suggests that disparities of depressive symptoms and education
      contribute to ethnic difference in the prevalence of dementia. CONCLUSIONS: These
      findings provide more insight into how ethnicity may influence an individual's
      vulnerability to dementia. The limitations of the study along with implications
      of the findings and needs for further study are discussed.

PMID- 23147389
TI  - Trends in psychotropic drug prescribing in Norwegian nursing homes from 1997 to
      2009: a comparison of six cohorts.
AB  - BACKGROUND: Psychotropic drugs are extensively prescribed for the treatment of
      neuropsychiatric symptoms, despite modest efficacy and severe side effects. AIMS:
      We examined trends in psychotropic drug prescribing in Norwegian nursing homes
      from 1997 to 2009, in order to gain insight in practice development. METHODS: The
      study is a secondary data analysis of six cross-sectional nursing home studies
      conducted between 1997 and 2009. Patients aged >65 years were included. We
      compared the prevalence of psychotropic drugs (antipsychotics, anxiolytics,
      hypnotics, and antidepressants). Associations between prescription of
      psychotropics, and patients' age, gender, type of ward, and year of data
      collection were examined by univariate analysis and logistic regression. RESULTS:
      Altogether, 7 661 patients (mean age 85.2 years, 72.6% women) were included.
      Prevalence of all psychotropic drugs combined increased from 57.6% to 70.5%,
      anxiolytics from 14.9% to 21.9%, hypnotics from 14.5% to 22.9%, and
      antidepressants from 31.5% to 50.9%. Prevalence of antipsychotics varied between
      extremes 21.1% and 25.6%. Less prescribing of older drugs was exceeded by an
      increase in newer drug types. Concomitant prescribing of two or more psychotropic
      drugs increased from 21% to 33%. Predictors of psychotropic drugs were female
      gender (except antipsychotics), as well as age <80 years, and residency in
      special care units (except hypnotics). CONCLUSIONS: Prescribing of psychotropic
      drugs in nursing homes has increased considerably, especially regarding
      antidepressants. Explanations for this trend need to be further explored.

PMID- 23147392
TI  - Catalytic activity of Co-N(x)/C electrocatalysts for oxygen reduction reaction: a
      density functional theory study.
AB  - First-principles DFT computations are performed to explain the origin and the
      mechanism of oxygen reduction reaction (ORR) on Co-N(x) (x = 2, 4) based self
      assembled carbon supported electrocatalysts in alkaline and acidic media. The
      results show that the formation of graphitic Co-N(4) defect is energetically more
      favorable than the formation of graphitic Co-N(2) defect. Furthermore graphitic
      Co-N(4) defects are predicted to be stable at all potentials (U = 0-1.23 V) in
      the present study while Co-N(2) defects are predicted to be unstable at high
      potentials. Therefore the Co-N(4) defect is predicted to be the dominant in-plane
      graphitic defect in Co-N(x)/C electrocatalysts. O(2) chemisorbs to Co-N(4) and Co
      N(2) defects indicating that both defect motifs are active for the reduction of
      O(2) to peroxide. However, the weak interaction between peroxide and Co-N(4)
      defect shows that this defect does not promote complete ORR and a second site for
      the reduction of peroxide is required, supporting a 2 * 2e(-) dual site ORR
      mechanism independent of pH of the electrolyte. In contrast, the much stronger
      interaction between peroxide and Co-N(2) defect supports a 2 * 2e(-) single site
      ORR mechanism in alkaline and acidic media.

PMID- 23147390
TI  - Combined and interactive effects of global climate change and toxicants on
      populations and communities.
AB  - Increased temperature and other environmental effects of global climate change
      (GCC) have documented impacts on many species (e.g., polar bears, amphibians,
      coral reefs) as well as on ecosystem processes and species interactions (e.g.,
      the timing of predator-prey interactions). A challenge for ecotoxicologists is to
      predict how joint effects of climatic stress and toxicants measured at the
      individual level (e.g., reduced survival and reproduction) will be manifested at
      the population level (e.g., population growth rate, extinction risk) and
      community level (e.g., species richness, food-web structure). The authors discuss
      how population- and community-level responses to toxicants under GCC are likely
      to be influenced by various ecological mechanisms. Stress due to GCC may reduce
      the potential for resistance to and recovery from toxicant exposure. Long-term
      toxicant exposure can result in acquired tolerance to this stressor at the
      population or community level, but an associated cost of tolerance may be the
      reduced potential for tolerance to subsequent climatic stress (or vice versa).
      Moreover, GCC can induce large-scale shifts in community composition, which may
      affect the vulnerability of communities to other stressors. Ecological modeling
      based on species traits (representing life-history traits, population
      vulnerability, sensitivity to toxicants, and sensitivity to climate change) can
      be a promising approach for predicting combined impacts of GCC and toxicants on
      populations and communities.

PMID- 23147391
TI  - Molecular and metabolic mechanisms of cardiac dysfunction in diabetes.
AB  - Diabetes mellitus type 2 (T2DM) is a widespread chronic medical condition with
      prevalence bordering on the verge of an epidemic. It is of great concern that
      cardiovascular disease is more common in patients with diabetes than the non
      diabetic population. While hypertensive and ischemic heart disease is more common
      in diabetic patients, there is another type of heart disease in diabetes that is
      not associated with hypertension or coronary artery disease. This muscle
      functional disorder is termed "diabetic cardiomyopathy". Diastolic dysfunction
      characterized by impaired diastolic relaxation time and reduced contractility
      precedes systolic dysfunction and is the main pathogenic hallmark of this
      condition. Even though the pathogenesis of "diabetic cardiomyopathy" is still
      controversial, impaired cardiac insulin sensitivity and metabolic overload are
      emerging as major molecular and metabolic mechanisms for cardiac dysfunction.
      Systemic insulin resistance, hyperinsulinemia, dysregulation of adipokine
      secretion, increases in circulating levels of inflammatory mediators, aberrant
      activation of renin angiotensin aldosterone system (RAAS), and increased
      oxidative stress contribute dysregulated insulin and metabolic signaling in the
      heart and development of diastolic dysfunction. In addition, maladaptive calcium
      homeostasis and endothelial cell dysregulation endoplasmic reticular stress play
      a potential role in cardiomyocyte fibrosis/diastolic dysfunction. In this review,
      we will focus on emerging molecular and metabolic pathways underlying cardiac
      dysfunction in diabetes. Elucidation of these mechanisms should provide a better
      understanding of the various cardiac abnormalities associated with diastolic
      dysfunction and its progression to systolic dysfunction and heart failure.

PMID- 23147393
TI  - Personality and physiological reactions to acute psychological stress.
AB  - Stable personality traits have long been presumed to have biological substrates,
      although the evidence relating personality to biological stress reactivity is
      inconclusive. The present study examined, in a large middle aged cohort (N=352),
      the relationship between key personality traits and both cortisol and
      cardiovascular reactions to acute psychological stress. Salivary cortisol and
      cardiovascular activity were measured at rest and in response to a psychological
      stress protocol comprising 5min each of a Stroop task, mirror tracing, and a
      speech task. Participants subsequently completed the Big Five Inventory to assess
      neuroticism, agreeableness, openness to experience, extraversion, and
      conscientiousness. Those with higher neuroticism scores exhibited smaller
      cortisol and cardiovascular stress reactions, whereas participants who were less
      agreeable and less open had smaller cortisol and cardiac reactions to stress.
      These associations remained statistically significant following adjustment for a
      range of potential confounding variables. Thus, a negative personality
      disposition would appear to be linked to diminished stress reactivity. These
      findings further support a growing body of evidence which suggests that blunted
      stress reactivity may be maladaptive. 

PMID- 23147394
TI  - Modulation of the startle reflex across time by unpleasant pictures distinguishes
      dysphoric from non-dysphoric women.
AB  - While several investigators have examined differences in affective startle
      modulation between individuals with and without Major Depressive Disorder, fewer
      researchers have evaluated the time course of this response, particularly in
      dysphoric individuals. The purpose of this study was to evaluate emotion
      modulation of the startle reflex during and after the presentation of affective
      pictures in dysphoric and non-dysphoric women. Dysphoric subjects showed
      attenuated startle for unpleasant compared to neutral pictures 1.5s post-stimulus
      onset relative to non-dysphoric subjects and potentiated startle for unpleasant
      compared to neutral pictures 3s post-stimulus offset. These findings extend the
      literature on the time course of affective startle modulation in dysphoria, and
      mirror results of studies in which other psychophysiological responses were
      examined in this population with regard to negative emotion.

PMID- 23147395
TI  - Clinical and genetic characterization of patients with arrhythmogenic right
      ventricular dysplasia/cardiomyopathy caused by a plakophilin-2 splice mutation.
AB  - OBJECTIVES: Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) is
      characterized by fibrofatty replacement of cardiomyocytes. In around 50% of index
      patients, a genetic predisposition is demonstrated. The purpose of this study was
      to examine a plakophilin-2 (PKP2) splice site mutation, c.2489+4A>C, identified
      in 4 separately ascertained Dutch ARVD/C families. METHODS: Genealogical studies
      and comprehensive screening of 5 desmosomal genes were undertaken. Reverse
      transcriptase PCR (RT-PCR) and subsequent sequencing was performed. RESULTS: An A
      to-C change (c.2489+4A>C) near the splice donor site of intervening sequence 12
      of PKP2 was found in all 4 families. Based on pedigree data and haplotype
      sharing, a common ancestor should be situated more than 7 generations ago. RT-PCR
      demonstrated the presence of aberrant messenger RNA. Clinical manifestations
      ranged from severe disease to nonpenetrance in elderly mutation carriers.
      CONCLUSIONS: This founder mutation in PKP2 is predicted to lead to the presence
      of a dysfunctional PKP2 protein, whereas most truncating mutations are expected
      to lead to loss of protein. Mutation carriers displayed a wide range of disease
      severity, suggesting that PKP2 mutations alone are not sufficient to cause
      disease, which results in the variable expression and incomplete penetrance
      characteristic of ARVD/C mutations.

PMID- 23147396
TI  - Van der Waals interaction-tuned heat transfer in nanostructures.
AB  - Interfaces usually impede heat transfer in heterogeneous structures. Recent
      experiments show that van der Waals (vdW) interactions can significantly enhance
      thermal conductivity parallel to the interface of a bundle of nanoribbons
      compared to a single layer of freestanding nanoribbon. In this paper, by
      simulating heat transfer in nanostructures based on a model of nonlinear one
      dimensional lattices interacting via van der Waals interactions, we show that the
      vdW interface interaction can adjust the thermal conductivity parallel to the
      interface. The efficiency of the adjustment depends on the intensity of
      interactions and temperature. The nonlinear dependence of the conductivity on the
      intensity of interactions agrees well with experimental results for carbon
      nanotube bundles, multi-walled carbon nanotubes, multi-layer graphene, and
      nanoribbons.

PMID- 23147397
TI  - Residential proximity to petroleum storage tanks and associated cancer risks:
      Double Kernel Density approach vs. zonal estimates.
AB  - BACKGROUND AND AIMS: The relationship between exposure to petroleum products and
      cancer is well-established in occupational studies carried out among employees of
      transportation and oil-producing industries. However, question remains whether
      living near petroleum storage facilities may represent a cancer risk. In the
      present study, we examined cancer incidence rates associated with residential
      proximity to the Kiryat Haim industrial zone in Northern Israel, using different
      analytical techniques and adjusting for several potential confounders, such as
      road proximity, population density, smoking rates and socio-demographic
      attributes. METHODS: Both traditional zonal approaches and more recently
      developed Double Kernel Density (DKD) tools were used to estimate relative risks
      of lung and NHL cancers attributed to residential proximity to the petroleum
      storage site. RESULTS: Zonal approaches based on comparing ASRs across small
      census areas (SCAs) did not detect any significant association between
      residential proximity to the industrial zone and the two types of cancers under
      study (P>0.2). In contrast, the DKD approach revealed that the relative density
      of both lung and NHL cancers declined in line with distances from the industrial
      zone, especially among the elderly (Lung: t>-12.0; P<0.01; NHL: t>-9.0; P<0.01),
      adjusted for proximity to main roads, population density, smoking rate, average
      income, and several other potential confounders. CONCLUSIONS: Living near
      petroleum storage sites may represent significant cancer risk which cannot always
      be detected by traditional zonal approaches commonly used in epidemiological
      studies, especially if the number of census areas available for the analysis is
      small.

PMID- 23147398
TI  - Involvement of BcVeA and BcVelB in regulating conidiation, pigmentation and
      virulence in Botrytis cinerea.
AB  - The heterotrimeric velvet complex VeA/VelB/LaeA is involved in the regulation of
      diverse cellular processes in Aspergillus nidulans. In this work, we investigated
      functions of two velvet-like genes BcVEA and BcVELB in Botrytis cinerea.
      Morphological characterization of BcVEA and BcVELB deletion mutants showed that
      the deletion of BcVEA and BcVELB led to increased conidiation and melanin
      biosynthesis. BcVEA and BcVELB deletion mutants also showed increased sensitivity
      to oxidative stress. Pathogenicity assays revealed that both BcVeA and BcVelB
      were essential for full virulence of B. cinerea. Yeast two-hybrid assay displayed
      the interaction of BcVeA with BcVelB. Results of this study indicate that BcVeA
      and BcVelB coordinate similar processes in the regulation of fungal development,
      oxidative stress response, and virulence in B. cinerea.

PMID- 23147399
TI  - Dual-compensated antisymmetric composite refocusing pulses for NMR.
AB  - Novel antisymmetric composite 180 degrees  pulses are designed for use in nuclear
      magnetic resonance (NMR) and verified experimentally. The pulses are
      simultaneously broadband with respect to both inhomogeneity of the radiofrequency
      (B(1)) field and resonance offset and, as a result of their antisymmetric phase
      schemes, can be used to form spin echoes without the introduction of a phase
      error. The new dual-compensated pulses are designed analytically, using symmetry
      arguments and a graphical interpretation of average Hamiltonian theory. Two
      families of composite refocusing pulses are presented, one (ASBO-9) consisting of
      sequences made up of 9 simple 180 degrees  pulses and one (ASBO-11) of sequences
      made up of 11 simple 180 degrees  pulses. There are an infinite number of
      composite pulses in each family owing to a free phase variable in the solution to
      the average Hamiltonian equations and this allows selection of individual
      composite pulses with particular properties. Finally, a comparison is made
      between composite pulses designed using average Hamiltonian theory and those
      proposed for use in quantum computing by NMR.

PMID- 23147400
TI  - Fasting time and lipid levels in a community-based population: a cross-sectional
      study.
AB  - BACKGROUND: Although current guidelines recommend measuring lipid levels in a
      fasting state, recent studies suggest that nonfasting lipid profiles change
      minimally in response to food intake and may be superior to fasting levels in
      predicting adverse cardiovascular outcomes. The objective of this study was to
      investigate the association between fasting times and lipid levels. METHODS:
      Cross-sectional examination of laboratory data, including fasting duration (in
      hours) and lipid results, was performed over a 6-month period in 2011 in a large
      community-based cohort. Data were obtained from Calgary Laboratory Services,
      Calgary, Alberta, Canada, the sole supplier of laboratory services for Calgary
      and surrounding areas (source population, 1.4 million persons). The main outcome
      measures were mean levels of high-density lipoprotein cholesterol, low-density
      lipoprotein cholesterol, total cholesterol, and triglycerides for fasting
      intervals from 1 hour to more than 16 hours. After differences in individual ages
      were controlled for, linear regression models were used to estimate the mean
      levels of cholesterol subclasses at different fasting times. RESULTS: A total of
      209,180 individuals (111,048 females and 98,132 males) were included in the
      study. The mean levels of total cholesterol and high-density lipoprotein
      cholesterol differed little among individuals with various fasting times. The
      mean calculated low-density lipoprotein cholesterol levels showed slightly
      greater variations of up to 10% among groups of patients with different fasting
      intervals, and the mean triglyceride levels showed variations of up to 20%.
      CONCLUSION: Fasting times showed little association with lipid subclass levels in
      a community-based population, which suggests that fasting for routine lipid
      levels is largely unnecessary.

PMID- 23147401
TI  - NADPH oxidase-derived reactive oxygen species are involved in the HL-60 cell
      monocytic differentiation induced by isoliquiritigenin.
AB  - The present study was undertaken to test the hypothesis that NADPH  oxidase
      derived reactive oxygen species (ROS) are involved in isoliquiritigenin  (ISL)
      induced monocytic differentiation in human acute promyelocytic leukemia HL-60
      cells. Morphological changes, cell surface markers CD11b/CD14 and NBT-reducing
      ability were used to determine the differentiation of HL-60 cells, and 2,7
      dichlorofluorescein  (DCFH-DA) was used to detect the level of intracellular ROS.
      ISL-induced  HL-60 cell differentiation was accompanied by an increase in the
      intracellular ROS  levels. l-Buthionine-(S,R)-sulfoximine (BSO), N-acetyl-l
      cysteine (NAC), superoxide  dismutase (SOD) and 4-hydroxy-2,2,6,6
      tetramethylpiperidinoxyl (Tempol) were used to interfere with ROS production.
      NADPH oxidase inhibitors, apocynin (APO) and diphenyleneiodonium (DPI) were used
      to study the role of NADPH oxidase in ISL-induced HL-60 cell differentiation. The
      ISL-induced HL-60 cell differentiation and intracellular ROS generation were
      enhanced by the oxidant BSO and inhibited by the antioxidants NAC, SOD, and
      tempol, and were also inhibited by the NADPH oxidase inhibitors APO and DPI. The
      protein and mRNA expression of the NADPH oxidase subunits gp91phox and p47phox
      were determined by Western blotting and RT-PCR, respectively. The levels of
      translation and transcription of the NADPH oxidase subunits gp91phox and p47phox
      increased markedly in a concentration-dependent manner. These findings suggest
      that NADPH oxidase plays a critical role in HL-60 cell differentiation induced by
      ISL and that NADPH oxidase-derived ROS is involved in the differentiation
      mechanism.

PMID- 23147402
TI  - New triterpenes from Maytenus robusta: structural elucidation based on NMR
      experimental data and theoretical calculations.
AB  - Leaves of Maytenus robusta (Celastraceae) were subjected to phytochemical
      investigation mainly directed at the isolation of pentacyclic triterpenes. The
      compounds friedelin (1), &#946;-friedelinol (2), 3-oxo-21&#946;-H-hop-22(29)-ene
      (7), 3,4-seco-friedelan-3,11&#946;-olide (8), 3&#946;-hydroxy-21&#946;-H-hop
      22(29)-ene (9), 3,4-seco-21&#946;-H-hop-22(29)-en-3-oic acid (10), 3,4-seco
      friedelan-3-oic acid (11), and sitosterol were identified in the hexane extract
      of M. robusta leaves. Compounds 8 and 9 are described herein for the first time.
      The structure and stereochemistry of both compounds were experimentally
      established by IR, HRLC-MS, and 1D (1H, 13C, and DEPT 135) and 2D (HSQC, HMBC and
      COSY) NMR data and supported by correlations with carbon chemical shifts
      calculated using the DFT method (BLYP/6-31G* level). Compounds 7 and 10 are also
      described for the first time, and their chemical structures were established by
      comparison with NMR data of similar structures described in the literature and
      correlations with BLYP/6-31G* calculated carbon chemical shifts. Compound 9, a
      mixture of 11 and sitosterol, and 3&#946;,11&#946;-dihydroxyfriedelane (4) were
      evaluated by the Ellman&#8217;s method and all these compounds showed
      acethylcholinesterase inhibitory properties.

PMID- 23147403
TI  - Quality controls in cellular immunotherapies: rapid assessment of clinical grade
      dendritic cells by gene expression profiling.
AB  - Cell-based immunotherapies are among the most promising approaches for developing
      effective and targeted immune response. However, their clinical usefulness and
      the evaluation of their efficacy rely heavily on complex quality control
      assessment. Therefore, rapid systematic methods are urgently needed for the in
      depth characterization of relevant factors affecting newly developed cell product
      consistency and the identification of reliable markers for quality control. Using
      dendritic cells (DCs) as a model, we present a strategy to comprehensively
      characterize manufactured cellular products in order to define factors affecting
      their variability, quality and function. After generating clinical grade human
      monocyte-derived mature DCs (mDCs), we tested by gene expression profiling the
      degrees of product consistency related to the manufacturing process and
      variability due to intra- and interdonor factors, and how each factor affects
      single gene variation. Then, by calculating for each gene an index of variation
      we selected candidate markers for identity testing, and defined a set of genes
      that may be useful comparability and potency markers. Subsequently, we confirmed
      the observed gene index of variation in a larger clinical data set. In
      conclusion, using high-throughput technology we developed a method for the
      characterization of cellular therapies and the discovery of novel candidate
      quality assurance markers.

PMID- 23147405
TI  - A further step towards tuning the properties of metal-chalcogenide nanocapsules
      by replacing skeletal oxide by sulphide ligands.
AB  - Addition of [Mo(2)(V)O(2)(MU-O)(MU-S)(aq)](2+) linker-type units to a
      solution/dynamic library containing tungstates results via the formation of the
      complementary pentagonal {(W)W(5)} units logically in the self-assembly of a
      mixed oxide/sulphide {W(VI)(72)Mo(V)(60)}-type Keplerate, thereby demonstrating
      the ability to tune the capsule's skeletal softness (the (MU-O)(2) and (MU-S)(2)
      scenarios are known) and providing options to influence differently important
      capsule-substrate interactions.

PMID- 23147404
TI  - Heart-brain signaling in patent foramen ovale-related stroke:  differential
      plasma proteomic expression patterns revealed with a 2-pass liquid chromatography
      tandem mass spectrometry discovery workflow.
AB  - Patent foramen ovale (PFO) is highly prevalent and associated with more than
      150,000 strokes per year. Traditionally, it is thought that PFOs facilitate
      strokes by allowing venous clots to travel directly to the brain. However, only a
      small portion of PFO stroke patients have a known tendency to form blood clots,
      and the optimal treatment for this multiorgan disease is unclear. Therefore,
      mapping the changes in systemic circulation of PFO-related stroke is crucial in
      understanding the pathophysiology to individualize the best clinical treatment
      for each patient. We initiated a study using a novel quantitative, 2-pass
      discovery workflow using high-resolution liquid chromatography-mass
      spectrometry/mass spectrometry coupled with label-free analysis to track protein
      expression in PFO patients before and after endovascular closure of the PFO.
      Using this approach, we were able to demonstrate quantitative differences in
      protein expression between both PFO-related and non-PFO-related ischemic stroke
      groups as well as before and after PFO closure. As an initial step in
      understanding the molecular landscape of PFO-related physiology, our methods have
      yielded biologically relevant information on the synergistic and functional
      redundancy of various cell-signaling molecules with respect to PFO circulatory
      physiology. The resulting protein expression patterns were related to canonical
      pathways including prothrombin activation, atherosclerosis signaling, acute-phase
      response, LXR/RXR activation, and coagulation system. In particular, after PFO
      closure, numerous proteins demonstrated reduced expression in stroke-related
      canonical pathways such as acute inflammatory response and coagulation signaling.
      These findings demonstrate the feasibility and robustness of using a proteomic
      approach for biomarker discovery to help gauge therapeutic efficacy in stroke.

PMID- 23147406
TI  - Bipolar versus monopolar transurethral resection of the prostate: results of a
      comparative, prospective bicenter study--perioperative outcome and long-term
      efficacy.
AB  - OBJECTIVES: To compare bipolar and monopolar transurethral resection of the
      prostate (TURP) in a comparative prospective study at two urology centers.
      METHODS: Of 212 patients with symptomatic benign prostatic hyperplasia entered
      prospectively into the study, 111 underwent bipolar and 101 monopolar TURP.
      Patients were treated in two consecutive series with each surgical method at both
      centers. Improvement in peak flow rate, postvoid residual, International Prostate
      Symptom Score, and quality of life score postoperatively and at 3, 12, 24 and 36
      months, as well as long-term adverse events were compared. Regarding safety,
      duration of surgery, postoperative catheterization and hospitalization time,
      amount of fluid absorption, frequency of transurethral resection (TUR) syndrome,
      and risk of hemorrhage were evaluated. RESULTS: Patient characteristics of the
      two series were comparable. The risk of developing TUR syndrome (p = 0.32) and
      bleeding tendency (p = 0.52) did not differ significantly between groups.
      Significant differences were seen for duration of surgery and resection speed.
      All functional parameters improved significantly during follow-up, with no
      relevant differences between surgical groups. CONCLUSIONS: Since no major
      differences in efficacy and safety were seen between the surgical groups, we feel
      that the monopolar technique still has a valuable place in TURP.

PMID- 23147409
TI  - The impact of chronic somatic diseases on the course of depressive and anxiety
      disorders.

PMID- 23147407
TI  - The IL-36 receptor pathway regulates Aspergillus fumigatus-induced Th1 and Th17
      responses.
AB  - IL-1 drives Th responses, particularly Th17, in host defense. Sharing the same co
      receptor, the IL-1 family member IL-36 exhibits properties similar to those of IL
      1. In the present study, we investigated the role of IL-36 in Aspergillus
      fumigatus-induced human Th responses. We observed that different morphological
      forms of A. fumigatus variably increase steady-state mRNA of IL-36 subfamily
      members. IL-36alpha is not significantly induced by any morphological form of
      Aspergillus. Most strikingly, IL-36gamma is significantly induced by live A.
      fumigatus conidia and heat-killed hyphae, whereas IL-36Ra (IL-36 receptor
      antagonist) is significantly induced by heat-killed conidia, hyphae, and live
      conidia. We also observed that IL-36gamma expression is dependent on the dectin
      1/Syk and TLR4 signaling pathway. In contrast, TLR2 and CR3 inhibit IL-36gamma
      expression. The biological relevance of IL-36 induction by Aspergillus is
      demonstrated by experiments showing that inhibition of the IL-36 receptor by IL
      36Ra reduces Aspergillus-induced IL-17 and IFN-gamma. These data describe that IL
      36-dependent signals are a novel cytokine pathway that regulates Th responses
      induced by A. fumigatus, and demonstrate a role for TLR4 and dectin-1 in the
      induction of IL-36gamma.

PMID- 23147408
TI  - Epidermal growth factor receptor transactivation is necessary for glucagon-like
      peptide-1 to protect PC12 cells from apoptosis.
AB  - AIM: Patients with long-standing diabetes commonly develop diabetic
      encephalopathy, which is characterized by cognitive impairment and dementia. To
      identify potential treatments for diabetic encephalopathy, we focused on the
      protective action of glucagon-like peptide-1 (GLP-1) against neural cell
      apoptosis. In this study, we evaluated whether exposure of cells to GLP-1 leads
      to epidermal growth factor receptor (EGFR) transactivation and signaling through
      the PI3K/Akt/mTOR/GCLc/redox pathway, which we previously reported. METHODS: We
      monitored the phosphorylation of EGFR and Akt in PC12 cells exposed to MG and GLP
      1 that had been first incubated in the presence or absence of various inhibitors
      of EGFR transactivation. RESULTS: DAPI staining revealed that pretreatment of
      cells with BiPS, HB-EGF and anti-TGF-alpha neutralization antibodies or AG1478
      abrogated the ability of GLP-1 to rescue cells from MG-induced apoptosis. We show
      that exposure of PC12 cells to GLP-1 induces EGFR phosphorylation and that this
      effect was inhibited by prior exposure of the cells to BiPS, HB-EGF and anti-TGF
      alpha neutralization antibodies or AG1478. Interestingly, these agents also
      diminished the capacity of GLP-1 to protect cells from MG-induced apoptosis.
      Moreover, these agents reduced GLP-1-induced phosphorylation of Akt. EGF itself
      also protected the cells from MG-induced apoptosis and induced phosphorylation of
      Akt, which was inhibited by LY294002. CONCLUSION: The neuroprotective effects of
      GLP-1 against MG-induced apoptosis are mediated by EGFR transactivation, which
      signals through the PI3K/Akt/mTOR/GCLc/redox pathway in PC12 cells.

PMID- 23147410
TI  - Fluorescence imaging of intracellular calcium signals in intact kidney tissue.
AB  - BACKGROUND: Intracellular calcium (Ca(2+)) plays an important role in normal
      renal physiology and in the pathogenesis of various kidney diseases; however, the
      study of Ca(2+) signals in intact tissue has been limited by technical
      difficulties, including achieving adequate loading of Ca(2+)-sensitive
      fluorescent dyes. The kidney slice preparation represents a model whereby three
      dimensional tissue architecture is preserved and structures in both the cortex
      and medulla can be imaged using confocal or multiphoton microscopy. METHODS:
      Ca(2+)-sensitive dyes Rhod-2, Fura-red and Fluo-4 were loaded into tubular and
      vascular cells in rat kidney slices using a re-circulating perfusion system and
      real-time imaging of Ca(2+) signals was recorded by confocal microscopy. Kidney
      slices were also obtained from transgenic mice expressing the GCaMP2 Ca(2+)
      sensor in their endothelial cells and real time Ca(2+) transients stimulated by
      physiological stimuli. RESULTS: Wide spread loading of Ca(2+) indicators was
      achieved in the tubular and vascular structures of both the medulla and cortex.
      Real time Ca(2+) signals were successfully recorded in different intracellular
      compartments of both rat and mouse cortical and medullary tubules in response to
      physiological stimuli (ATP and angiotensin II). Glomerular Ca(2+) transients were
      similarly recorded in kidney slices taken from the transgenic mouse expressing
      the GCaMP2 Ca(2+)-sensor. CONCLUSION: We present new approaches that can be
      adopted to image cytosolic and mitochondrial Ca(2+) signals within various cell
      types in intact kidney tissue. Moreover, techniques described in this study can
      be used to facilitate future detailed investigations of intracellular Ca(2+)
      homeostasis in renal health and disease.

PMID- 23147411
TI  - Thermo-sensitive gels containing lorazepam microspheres for intranasal brain
      targeting.
AB  - Thermo-sensitive gels containing lorazepam microspheres were developed and
      characterized for intranasal brain targeting. Pluronics (PF-127 and PF-68) have
      been selected since they are thermo-reversible polymers with the property of
      forming a solution at low temperatures (4-5  degrees C), and a gel at body
      temperature (37  degrees C). This property makes them an interesting material to
      work with, especially in case of controlled release formulations. The present
      study focuses on the development of an intranasal formulation for lorazepam, as
      an alternative route of drug delivery to the brain. Direct transport of drugs to
      the brain circumventing the brain barrier, following intranasal administration,
      provides a unique feature and better option to target brain. The presence of
      mucoadhesive microspheres in the gel vehicle via nasal route can achieve a dual
      purpose of prolonged drug release and enhanced bioavailability. To optimise the
      microsphere formulation, Box Behnken design was employed by investigating the
      effect of three factors, polymer concentration (chitosan), emulsifier
      concentration (Span 80) and cross-linking agent (glutaraldehyde) on the response
      variable which is the mean particle size. The concentration of 21% PF-127 and 1%
      PF-68 were found to be promising gel vehicles. The results showed that the
      release rate followed a prolonged profile dispersion of the microspheres in the
      viscous media, in comparison to the microspheres alone. Histopathological studies
      proved that the optimised formulation does not produce any toxic effect on the
      microscopic structure of nasal mucosa.

PMID- 23147413
TI  - Anesthetic effects on susceptibility to cortical spreading depression.
AB  - Cortical spreading depression (CSD) is a transient neuronal and glial
      depolarization and disruption of membrane ionic gradients that propagates slowly
      across the cerebral cortex. Recent clinical and experimental evidence has
      implicated CSD in the pathophysiology of migraines and neuronal injury states. In
      the current study, we examined the influence of four different anesthetics
      (propofol, dexmedetomidine, isoflurane, pentobarbital) on CSD susceptibility in a
      KCl application animal model. We found that isoflurane and dexmedetomidine
      suppressed CSD frequency, and tended to reduce the CSD propagation speed. Our
      data suggest that these anesthetics may be therapeutically beneficial in
      preventing CSD in diverse neuronal injury states.

PMID- 23147412
TI  - Neuroendocrine phenotype alteration and growth suppression through apoptosis by
      MK-2206, an allosteric inhibitor of AKT, in carcinoid cell lines in vitro.
AB  - Carcinoids are neuroendocrine malignancies characterized by their overproduction
      of various bioactive hormones that lead to the carcinoid syndrome. We have shown
      previously that AKT serves as a key regulator of growth and phenotypic expression
      of tumor markers in carcinoids by the genetic depletion of AKT expression.
      However, no small-molecule inhibitor of AKT kinase activity has been developed
      until recently. MK-2206, a novel allosteric inhibitor of AKT, is currently
      undergoing clinical trials for the treatment of solid tumors. In this study, we
      explored the effect of MK-2206 on carcinoid cell proliferation and bioactive
      hormone production in vitro in two carcinoid cell lines - pancreatic carcinoid
      BON and bronchopulmonary H727. Treatment with MK-2206 effectively suppressed AKT
      phosphorylation at serine 473 and significantly reduced cell proliferation in a
      dose-dependent manner. Most importantly, MK-2206 treatment resulted in a
      significant reduction in ASCL1, CgA, and NSE expression, collectively recognized
      as markers of neuroendocrine tumor malignancy. Furthermore, MK-2206-treated cells
      showed an increase in levels of cleaved PARP and cleaved caspase-3, with a
      concomitant reduction in levels of Mcl-1 and XIAP, indicating that the
      antiproliferative effect of MK-2206 occurs through the induction of apoptosis. In
      conclusion, MK-2206 suppresses carcinoid tumor growth, and alters its
      neuroendocrine phenotype, indicating that this drug may be beneficial for
      patients with carcinoid syndrome. These studies merit further clinical
      investigation.

PMID- 23147415
TI  - Mice heterozygous for AChE are more sensitive to AChE inhibitors but do not
      respond to BuChE inhibition.
AB  - An impaired central cholinergic system is at least partly involved in Alzheimer's
      disease (AD) pathogenesis, with cholinergic markers such as acetylcholinesterase
      (AChE) activity and protein levels decreasing as cognitive decline progresses. AD
      patients receive AChE inhibitor drugs to enhance cholinergic responses in the
      brain. The present study characterises the cholinergic system of mice
      heterozygous for AChE (HZ) as a suitable in vivo model for permanently reduced
      AChE activity. In comparison to homozygous, wild type (WT) mice, HZ mice show a
      40% reduction of AChE activity in the brain, while their hippocampal ACh levels
      are increased by 56% as measured by microdialysis; choline acetyltransferase
      levels remain unaltered, and choline uptake increases 2-fold. We demonstrate that
      HZ mice are significantly more sensitive to local AChE inhibition (BW284c51), but
      remain insensitive to butyrylcholinesterase (BuChE) inhibition (bambuterol). HZ
      mice are also more sensitive to the peripheral application of the selective AChE
      inhibitor donepezil or the mixed inhibitor physostigmine; extracellular ACh
      levels rise significantly after administration of both drugs; also glucose levels
      are moderately increased indicating potentially non-cholinergic effects of
      donepezil. Behavioural tests show comparable cognitive function in both mouse
      strains. Our results are discussed in relation to the use of AChE/BuChE
      inhibitors in AD patients.

PMID- 23147414
TI  - Linking GABA(A) receptor subunits to alcohol-induced conditioned taste aversion
      and recovery from acute alcohol intoxication.
AB  - GABA type A receptors (GABA(A)-R) are important for ethanol actions and it is of
      interest to link individual subunits with specific ethanol behaviors. We studied
      null mutant mice for six different GABA(A)-R subunits (alpha1, alpha2, alpha3,
      alpha4, alpha5 and delta). Only mice lacking the alpha2 subunit showed reduction
      of conditioned taste aversion (CTA) to ethanol. These results are in agreement
      with data from knock-in mice with mutation of the ethanol-sensitive site in the
      alpha2-subunit (Blednov et al., 2011). All together, they indicate that aversive
      property of ethanol is dependent on ethanol action on alpha2-containing GABA(A)
      R. Deletion of the alpha2-subunit led to faster recovery whereas absence of the
      alpha3-subunit slowed recovery from ethanol-induced incoordination (rotarod).
      Deletion of the other four subunits did not affect this behavior. Similar changes
      in this behavior for the alpha2 and alpha3 null mutants were found for flurazepam
      motor incoordination. However, no differences in recovery were found in motor
      incoordinating effects of an alpha1-selective modulator (zolpidem) or an alpha4
      selective agonist (gaboxadol). Therefore, recovery of rotarod incoordination is
      under control of two GABA(A)-R subunits: alpha2 and alpha3. For motor activity,
      alpha3 null mice demonstrated higher activation by ethanol (1 g/kg) whereas both
      alpha2 (-/-) and alpha3 (-/Y) knockout mice were less sensitive to ethanol
      induced reduction of motor activity (1.5 g/kg). These studies demonstrate that
      the effects of ethanol at GABAergic synapses containing alpha2 subunit are
      important for specific behavioral effects of ethanol which may be relevant to the
      genetic linkage of the alpha2 subunit with human alcoholism.

PMID- 23147416
TI  - Decreased pain responses of C-C chemokine receptor 5 knockout mice to chemical or
      inflammatory stimuli.
AB  - Chemokines are small chemotactic cytokines that elicit many physiological and
      pathological effects through binding to their corresponding receptors. Recent
      studies have suggested that C-C chemokine receptor (CCR) 5 interacts with MU
      opioid receptor and modifies a nociceptive reaction. We examined effects of CCR5
      deficiency on pain responses by employing CCR5 knockout (KO) mice. We found that
      pain responses of CCR5 KO mice to chemical or inflammation stimuli were milder
      than those of CCR5 wild type (WT) mice. However, there was no remarkable change
      in thermal nociception. To prove the involvement of CCR5 deletion in lowered
      nociception, we examined pain reactions with CCR5 WT mice following treatment of
      a CCR5 antagonist (D-Ala(1)-peptide T-NH(2,) DAPTA). Chemical or inflammatory
      pain behavior was significantly relieved by intracerebroventricular infusion of
      the inhibitor. When we assessed expression level of MU-opioid receptor (MOR) in
      the periaqueductal gray where the receptors are critical for analgesic effects,
      immunoreactivity of MOR was significantly higher in CCR5 KO mice than WT mice
      without change in phosphorylation level of the receptor. Reduced nociceptive
      responses in CCR5 KO mice were moderated by administration of naloxone and d-Phe
      Cys-Tyr-d-Trp-Arg-Thr-Pen-Thr-NH2 (CTAP), MOR antagonists. Our data indicate that
      CCR5 deficiency is related to up-regulation of MOR without an increase in the
      receptor desensitization which might result in increased analgesic effects
      against chemical or inflammatory stimuli. Alternatively, higher amount of opioid
      ligands in CCR5 mice might be linked to these results. Therefore, CCR5 appears to
      be a therapeutic target for treatment of pain related diseases such as
      inflammatory hyperalgesia.

PMID- 23147417
TI  - Orexin A regulates cardiovascular responses in stress-induced hypertensive rats.
AB  - Several pieces of evidence indicate that the rostral ventrolateral medulla (RVLM)
      is probably one of the key neural structures mediating the pressor effects of
      orexins in the brain. Nitric oxide synthase/nitric oxide (NOS/NO) system in the
      RVLM modulates cardiovascular activities. Our experiments were designed to test
      the hypothesis that orexin-A (OXA) is involved in the mechanism of stress-induced
      hypertension (SIH) by adjusting NOS/NO system in the RVLM. The stress-induced
      hypertensive rats (SIHR) model was established by electric foot-shocks and
      noises. Here we examined the expression of OXA immunoreactive (OXA-IR) cells in
      the lateral hypothalamus (LH) and the protein level of orexin 1 receptor (OX1R)
      in the RVLM of SIHR, and we found that the expressions of OXA-IR and OX1R were
      higher than those of the control group. The double-staining immunohistochemical
      evidence showed that OX1R immunoreactive (OX1R-IR) cells and neuronal nitric
      oxide synthase (nNOS) or inducible nitric oxide synthase (iNOS) immunoreactive
      (IR) cells were co-localizated in the RVLM. Microinjection of OXA (10, 50, 100
      pmol/100 nl) into the unilateral (right) RVLM of control rats or SIHR produced
      pressor and tachycardiac effects in a dose-dependent manner. SB-408124 (100
      pmol/100 nl, an antagonist of OX1R) or TCS OX2 29 (100 pmol/100 nl, an antagonist
      of OX2R) partly abolished the cardiovascular effects of exogenously-administrated
      OXA into the RVLM of control rats and SIHR, and lowered the increased systolic
      blood pressure (SBP) and heart rate (HR) of SIHR, with no difference in
      statistical significance between the two antagonists' effects. Microinjection
      into the RVLM of both control and SIHR groups of 7-Ni (0.05 pmol/100 nl, nNOS
      inhibitor) or Methylene Blue [100 pmol/100 nl, an inhibitor of soluble guanylate
      cyclase (sGC)] suppressed the OXA-induced increase of SBP and HR, whereas
      microinjection of AG (1, 10, 100 pmol/100 nl) had no obvious effects on the OXA
      induced increase of SBP and HR. Our results indicate that OXA in the RVLM may
      participate in the central regulation of cardiovascular activities in SIHR, and
      OX1R and OX2R both have important roles in it. The cardiovascular effects of OXA
      in the RVLM may be induced by nNOS-derived NO, which activated sGC-associated
      signaling pathway.

PMID- 23147418
TI  - Transition-metal-mediated activation of the heptaarsenide trianion: isolation of
      a diaryltetraarsenabutadienediide.
AB  - Reaction of an ethylenediamine solution of K(3)As(7) with the low-valent, low
      coordinate cobalt(II) complex [Co(mes)(2)(PEt(2)Ph)(2)] yielded the novel
      dianionic species [Co(eta(3)-As(3)){eta(4)-As(4)(mes)(2)}](2-) (1). The [eta(4)
      As(4)(mes)(2)](2-) moiety present in 1 is a rare example of a group 15 analogue
      of a butadienediide.

PMID- 23147419
TI  - Behavioral and psychological subsyndromes in Alzheimer's disease using the
      Neuropsychiatric Inventory.
AB  - OBJECTIVE: Behavioral and psychological symptoms of dementia represent common
      clinical features of dementias, contributing to the heterogeneous phenotypic
      expression of Alzheimer's disease (AD). During the last two decades, several
      studies explored the possible presence of neuropsychiatric subsyndromes in
      dementia by examining the internal structure of the Neuropsychiatric Inventory
      (NPI). The aim of the present review is to present available evidence coming from
      studies adopting factor analysis to explore the NPI and describe neuropsychiatric
      clusters of symptoms in AD. DESIGN: A systematic review of literature was
      performed concerning available studies describing neuropsychiatric subsyndromes
      in AD by adopting the NPI. RESULTS: Overall, our analysis showed a relatively low
      concordance among available evidence for what concerns the definition and
      composition of NPI clusters, possibly due (at least in part) to the heterogeneity
      of the sample populations recruited in the studies. However, we also observed
      some consistent associations of specific symptoms across studies, defining
      potential subsyndromes in AD. More consistent results were obtained by studies
      evaluating the 10-item version of the NPI rather than the more recent 12-item
      one. CONCLUSIONS: This review represents the first attempt to systematically
      evaluate evidence coming from factor analyses exploring the internal structure of
      the NPI in order to facilitate the identification of neuropsychiatric syndromes
      in AD patients. The NPI may support the definition of behavioral subsyndromes in
      AD. The evaluation of neuropsychiatric subsyndromes should always take into
      account the main potential confounders, such as age, severity of disease, and
      concomitant pharmacological treatment.

PMID- 23147421
TI  - Association of lean and fat body mass, bone biomarkers and gonadal steroids with
      bone mass during pre- and midpuberty.
AB  - BACKGROUND/AIMS: The association of bone mass with body composition, bone
      turnover markers and gonadal steroids was examined in Hungarian children during
      pre- and midpuberty. METHODS: Two hundred and thirty-seven 7- to 16-year-old
      subjects (56% girls) were investigated. Bone mineral density (BMD), fat mass and
      total and appendicular lean mass were estimated with dual-energy X-ray
      absorptiometry (Lunar Prodigy). The fat mass index and appendicular lean mass
      index (LMI) were calculated. Serum bone markers, parathyroid hormone, estradiol
      and testosterone were analyzed. Associations between variables were evaluated by
      multiple regression analysis. RESULTS: During prepuberty, bone biomarkers,
      gonadal steroids and appendicular LMI were associated with bone mass in both
      genders (p < 0.05). During midpuberty, girls' bone turnover markers were
      negatively associated with bone mass (p < 0.001). In prepuberty, appendicular LMI
      and beta-crosslaps were predictors of bone mass in both genders. During
      midpuberty, appendicular LMI and gonadal steroids positively contributed to bone
      mass in both genders, while osteocalcin exerted a negative influence on total and
      L1-L4 spine BMD in girls and on L1-L4 BMD in boys (all p < 0.001). CONCLUSIONS:
      Predictors for bone development varied according to Tanner stage and gender. The
      most significant determinants of bone mass were appendicular LMI and estradiol.

PMID- 23147422
TI  - Transcriptional analysis and proteomics of the holomycin gene cluster in
      overproducer mutants of Streptomyces clavuligerus.
AB  - Expression of the holomycin biosynthesis genes (hlm) has been studied in the wild
      type strain Streptomyces clavuligerus ATCC 27064 and holomycin overproducer
      mutants. RT-PCR transcription analysis of S. clavuligerus oppA2::aph showed a
      higher transcription of the hlmA, B, C, D, E, F, G, H, I and hlmL genes, a
      slightly lower expression for hlmK and no significant differences for the
      transcription of the two putative regulatory genes, hlmM and hlmJ, in relation to
      the wild type strain. Accordingly, protein spots corresponding to HlmD, HlmF and
      HlmG, which were barely detectable in the wild type strain, were present in high
      amounts in the holomycin overproducer S. clavuligerus oppA2::aph proteome.
      Transcription start point analysis of the hlm genes revealed that the annotated
      sequences in the databases for several hlm genes were incorrect. The hlm cluster
      was introduced into Streptomyces coelicolor M1154 and holomycin production by S.
      coelicolor M1154 [pVR-hol1] was validated by bioassays and confirmed by HPLC
      analysis and mass spectrometry. Heterologous holomycin production by the S.
      coelicolor transformant is 500-fold lower than in S. clavuligerus oppA2::aph. The
      transformant S. coelicolor M1154 [pVR-hol1] shows holomycin sensitivity to 100
      MUg/ml, similar to that of the parental S. coelicolor M1154 strain, suggesting
      that heterologous expression in S. coelicolor might be toxic due to the lack of
      an holomycin resistance gene in this host strain.

PMID- 23147420
TI  - Implications of global climate change for the assessment and management of human
      health risks of chemicals in the natural environment.
AB  - Global climate change (GCC) is likely to alter the degree of human exposure to
      pollutants and the response of human populations to these exposures, meaning that
      risks of pollutants could change in the future. The present study, therefore,
      explores how GCC might affect the different steps in the pathway from a chemical
      source in the environment through to impacts on human health and evaluates the
      implications for existing risk-assessment and management practices. In certain
      parts of the world, GCC is predicted to increase the level of exposure of many
      environmental pollutants due to direct and indirect effects on the use patterns
      and transport and fate of chemicals. Changes in human behavior will also affect
      how humans come into contact with contaminated air, water, and food. Dietary
      changes, psychosocial stress, and coexposure to stressors such as high
      temperatures are likely to increase the vulnerability of humans to chemicals.
      These changes are likely to have significant implications for current practices
      for chemical assessment. Assumptions used in current exposure-assessment models
      may no longer apply, and existing monitoring methods may not be robust enough to
      detect adverse episodic changes in exposures. Organizations responsible for the
      assessment and management of health risks of chemicals therefore need to be more
      proactive and consider the implications of GCC for their procedures and
      processes.

PMID- 23147423
TI  - Establishment of an efficient genetic transformation system in Scenedesmus
      obliquus.
AB  - Scenedesmus obliquus belongs to green microalgae, which is attracting attention
      as a feedstock for biofuels production and biorefinery as well as in
      bioremediation of environmental pollutants, making its genetic modifications for
      more efficient growth and accumulation of aimed metabolites significant. However,
      the genetic transformation system of S. obliquus is still not well established.
      In the current work, S. obliquus was transformed via electroporation using a
      plasmid containing chloramphenicol resistance gene (CAT) as a selectable marker
      and the green fluorescent protein gene (gfp) as a reporter. Using the optimized
      transformation conditions, the transformation efficiency was 494+/-48 positive
      transgenic clones per 10(6) recipient cells, which is more efficient comparing
      with those reported in other microalgal transformation studies. Green
      fluorescence was observed after six months of cultivation, and CAT-specific
      products were also detected in the transformants by PCR, Southern blot and RT-PCR
      analysis. This is the first report on establishing such an efficient and stable
      transformation system for S. obliquus, a prerequisite for both functional genomic
      studies and strain improvement for other biotechnology applications of this
      important microalgal species.

PMID- 23147424
TI  - Project PriMo: sharing principles and practices of bronchodilator therapy
      monitoring in COPD: a consensus initiative for optimizing therapeutic
      appropriateness among Italian specialists.
AB  - BACKGROUND: Even after publication of the 2011 update of GOLD report, some
      fundamental questions in the management of COPD are still open and this may
      weaken the applicability of these guidelines in everyday clinical practice.
      OBJECTIVE: To assess the level of consensus amongst Italian respirologists on
      different topics related to diagnosis, monitoring and role of bronchodilator
      therapy in COPD, by using the Delphi technique. METHODS: A Delphi study was
      undertaken between July and November 2011, when two questionnaires were
      consecutively sent to a panel of experts to be answered anonymously. After each
      round, the data were aggregated at group level of question topics and structured
      feedback was given to the panel. RESULTS: A first-round questionnaire was sent to
      208 pulmonologists randomly selected from different Italian regions. The 132
      respondents (63% of those initially selected) were from northern (53%), central
      (19%) and southern (28%) Italy. A second-round questionnaire was sent to all the
      first-round respondents, and a response was received from 110 of them (83%). The
      main topics that reached the pre-defined cut off for consensus (67% or more)
      were: a) bronchodilator therapy with long-acting bronchodilators could be
      beneficial in patients with airflow limitation even in the absence of symptoms,
      b) in patients not fully controlled with one long-acting bronchodilator,
      maximizing bronchodilation (i.e. adding another bronchodilator with a different
      mechanism of action) is the preferable option; and c) the use of inhaled
      corticosteroids (ICSs) as add on therapy should be considered in severe patients
      with frequent exacerbations. CONCLUSIONS: Italian specialists agree on several
      aspects of the diagnosis and treatment of COPD and expert opinion could support
      everyday decision process in the management of COPD.

PMID- 23147433
TI  - Very long-term outcome of peripheral arterial disease in patients undergoing
      percutaneous coronary revascularization: a retrospective analysis.
AB  - AIM: Peripheral arterial disease (PAD) in patients undergoing percutaneous
      coronary intervention (PCI) with stent implantation is a well known risk factor
      leading to an increased rates of stroke, cardiovascular death and myocardial
      infarction. Anyway there are few data on very-long term outcome (more than 1 year
      follow up) of PAD after stent implantation. We thus aimed to evaluate the
      influence of PAD on very long-term outcome of our PCI-population. METHODS: We
      retrospectively identified all patients undergoing PCI with stent implantation at
      our center between July 2002 and June 2004, and thus eligible for at least 4
      years of follow-up. For the purpose of this study, we considered a diagnosis of
      PAD based on clinical evaluation and/or angiographic documentation. We
      adjudicated the following clinical events: death, myocardial infarction, repeat
      revascularization, and their composite (i.e. major adverse cardiac events, MACE).
      RESULTS; A total of 1008 patients were included, 109 with PAD and 899 Without
      PAD. Those with had more often diabetes (35% vs. 25%, P=0.002), hypertension (83%
      vs. 68%, P=0.001) and unfavorable basal clinical condition at the start of this
      study: past-Percutaneous Coronary Intervention (PCI) (30% vs. 22%, P=0.005), past
      Coronary Artery Bypass Graft (CABG) (24% vs. 14%, P=0.001), ejection fraction
      (EF) <35% (14% vs. 7%, P=0.02) and chronic renal failure (CRF) (15% vs. 6%,
      P=0.002). In addiction patient with PAD were more likely to have chronic total
      occlusion (CTO) (36% vs. 25%, p=0.02) and unprotected left main (16% vs.
      8%,P=0.01). Clinical outcome at the time of follow-up (4,42 +/- 1,66 years) was
      as follow: Revascularization (53% vs. 37%, P=0.002), Cardiac death (21% vs. 13%,
      P=0.04), MACE (69% vs. 49%, p<.001). Independent predictors of MACE according to
      our survival analysis were: PAD (HR 1.31; 95% CI 1.01-1.69), Age >75 (HR 1.23;
      95% CI 1-1.51), Chronic heart failure (HR1.72; 95% CI 1.19-2.5), Unprotected left
      main (HR 1.48; 95% CI 1.12-1.96). CONCLUSION: This long-term registry shows that
      PAD remains an important clinical condition that negatively influences the
      outcome of patients undergoing PCI with stent implantation in a very long-term
      follow-up period.

PMID- 23147434
TI  - Predictors of mortality in patients undergoing percutaneous aortic valve
      implantation.
AB  - AIM: Transcatheter aortic valve implantation (TAVI) became an attractive
      alternative to surgery for patients with severe aortic stenosis and high
      operative risk. The first multicenter randomized trial, conducted in such high
      risk cohort, showed 20% reduction in mortality in the group treated with TAVI
      compared to those treated with medical therapy (30.7% vs. 50.7% P=0.001) and a
      non-inferiority of TAVI compared to traditional valve surgical replacement for
      all-cause mortality at 1 year with, similar improvement of symptoms and physical
      performance. However, mortality rate of TAVI remains high (20-30% at one year).
      The purpose of this prospective single center study was to identify predictors of
      mortality and adverse events in patients undergoing TAVI in order to be able to
      select the ones who benefit most from the procedure. METHODS: Between June 2009
      and June of 2011, 118 patients with severe aortic stenosis treated with TAVI at
      IRCCS Humanitas Clinical Institute were included in a prospective registry. Pre
      procedural clinical and ecocardiographic evaluations, surgical risk estimation,
      and procedural complications, defined by VASC criteria, were recorded. Clinical
      and echocardiographic evaluations were performed at 1, 6 and 12 months after the
      implants. To investigate the predictors of mortality, clinical and anatomical
      characteristics of alive patients were compared with those of death ones at one
      month and one year follow-up. RESULTS: The procedural success occurred in 92.4%
      of procedures; vascular complications (33%), bleeding complications (22%),
      postimplant paravalvolar grade >=2 AR (20.4%) a new permanent pacemaker implant
      (19.7%), were the most common complications. Survival for the whole cohort at 30
      days was 6.8%, survival at one year was 82.2%. In the logistic regression test,
      one month mortality was significantly adversely affected by the renal functional
      status (odd ratio 0.9356), by a previous history of coronary artery bypass
      grafting (odd ratio 39) and by the mean aortic annular diameter (odd ratio 0.512)
      (P=0.0005). One year mortality was influenced by high EuroSCORE (odd ratio
      1.0399) and the presence of hemodynamically significant prosthetic regurgitation
      (odd ratio 3.8438). CONCLUSION: TAVI procedure, in high risk patients with
      critical aortic stenosis, can be accomplished with low procedural mortality. The
      worst outcome affects particularly patients with renal insufficiency and previous
      coronary bypass. However, the long-term mortality remains high due to the poor
      baseline conditions, mainly related to co-morbidity and to the presence of
      residual post-procedural aortic insufficiency.

PMID- 23147435
TI  - Short and long term outcome of percutaneous coronary intervention with drug
      eluting stent and bare metal stent in patients with chronic kidney disease.
AB  - AIM: Coronary artery disease represents the most important cause of mortality and
      morbidity in chronic kidney disease (CKD). Despite continuous improvements in
      percutaneous coronary intervention (PCI), CKD is still associated with more
      adverse events after PCI. We performed a retrospective study to compare bare
      metal stents (BMS) versus drug eluting stents (DES) in CKD. METHODS: We included
      consecutively all patients undergoing PCI at our Centre from July 2002 to
      December 2005 with CKD, defined as creatinine clearance <60 mL/min. Patients who
      received only DES were compared to those who received only BMS. The primary end
      point was the long-term rate of major adverse cardiac events (MACE, i.e. the
      composite of death, myocardial infarction and repeat revascularization). RESULTS:
      We included a total of 219 patients with CKD out of a total of 2354 patients,
      with 164 receiving BMS and 55 DES. After a mean follow up of 48 months, the MACE
      rate was significantly higher in BMS group (71% versus 38%, P<0.001). A similarly
      increased risk with BMS was found for death (45% versus 17%, P<0.001), whereas
      the rates for repeat coronary revascularization, myocardial infarction and stent
      thrombosis were not significantly different. Multivariable analysis showed that
      BMS vs.. DES implantation was not statistically significant associated with MACE,
      death, myocardial infarction, rePTCA or stent thrombosis. CONCLUSION: Compared
      with BMS, use of DES in patients with CKD is safe and effective in reducing
      adverse outcomes. However, differences found between groups in clinical end-point
      could be ascribed to selection bias and confounding factors.

PMID- 23147436
TI  - Assessment of left ventricular systolic and diastolic dyssynchrony with tissue
      Doppler echocardiography in patients with heart failure and narrow QRS complex.
AB  - AIM: Cardiac dyssynchrony is a well known entity in patients with wide QRS
      complex (>120 ms). Dyssynchrony may also cause ventricular dysfunction in heart
      failure patients with narrow QRS complexes. In the study, the presence and extent
      of cardiac dyssynchrony were investigated in patients with heart failure both
      with narrow and wide QRS complexes using tissue Doppler echocardiography (TDE).
      METHODS: Forty-nine patients with heart failure, were included to the study. The
      first group of 30 patients with a QRS duration of <120 ms (23M; mean age, 64+/
      10.1 years) and the second group consisted of 19 patients with a QRS duration of
      >120 ms (12M; mean age, 65+/-11.6 years). In order to examine cardiac
      synchronization, TDE was performed. Systolic and diastolic intraventricular
      dyssynchrony and interventricular dyssynchrony were calculated. In order to
      define systolic and diastolic dyssynchrony, intraventricular delay was accepted
      as >60 ms, and interventricular delay was accepted as >40 ms. RESULTS: Left
      ventricular systolic dyssynchrony was detected in 18 patients (60%) within the
      narrow QRS group and in 18 patients (94%) within the wide QRS group.
      Interventricular dyssynchrony was detected in 17 patients (56%) within the narrow
      QRS group and in 18 patients (94%) within the wide QRS group. For systolic
      dyssynchrony, correlations existed between intraventricular delay and QRS
      duration (r=0.48), left ventricular end diastolic diameter (r=0.62), left
      ventricular end systolic diameter (r=0.61), and EF (r=-0.63). Similarly,
      correlations existed between interventricular delay and QRS duration (r=0.58),
      left ventricular end diastolic diameter (r=0.65), left ventricle end systolic
      diameter (r=0.64), and EF (r=-0.64). CONCLUSION: The present study suggested that
      systolic or diastolic dyssynchrony exists despite normal levels of QRS duration.

PMID- 23147437
TI  - Heart failure: molecular, genetic and epigenetic features of the disease.
AB  - Factors that compete to establish heart failure (HF) are not completely known. In
      the last years the several technological improvements allowed us to deeply study
      the molecular and genetic aspects of this complex syndrome. This new approach to
      HF based on molecular biology new discoveries shows us more clearly the
      pathophysiological bases of this disease, and a future scenery where the genetics
      may be useful in the clinical practice, as screening of high risk populations, as
      well as in the diagnosis and therapy of underlying myocardial diseases. The
      purpose of this review was to analyse the molecular, genetic and epigenetic
      factors of HF. We described the molecular anatomy of the sarcomere and the
      pathogenesis of the heart muscle diseases, abandoning the previous monogenic
      theory for the concept of a polygenic disease. Different actors play a role to
      cause the illness by themselves, modifying the expression of the disease and,
      eventually, the prognosis of the patient.

PMID- 23147438
TI  - Dual antiplatelet therapy for primary and secondary prevention.
AB  - The concomitant use of aspirin and an ADP receptor (P2Y12) blocker, also known as
      dual antiplatelet therapy (DAPT), has been extensively investigated as a primary
      and secondary prevention strategy in an effort to reduce the risk of
      cardiovascular events. In this manuscript the authors review the current
      guideline recommendations for DAPT and discuss the scientific data that supports
      these recommendations. Reported are also the scientific knowledge gaps and how
      future studies are likely to delineate these issues. Incremental knowledge is not
      likely to be an alternative to individualized care provided by the astute
      clinician to his patient. In consideration for prescribing DAPT (drug, dosage and
      duration) the clinician will have to weigh the potential benefits (reduction in
      death from cardiovascular causes, nonfatal myocardial infarction, and nonfatal
      stroke) and risks (severe or life-threatening bleeding) for each and every
      patient.

PMID- 23147439
TI  - Long-term patient benefit with biodegradable polymer biolimus eluting stent.
AB  - The introduction of bare metal stents in the early 1990 and of 1st generation
      drug eluting stents (DES) in the early 2000 defined a new era in interventional
      cardiology. DES dramatically reduced instant restenosis and the need of
      revascularization after percutaneous coronary intervention. However, this
      increased efficacy came at the cost of delayed vascular healing and subsequent
      late adverse event such as late stent thrombosis. Second generation DES appears
      even more efficient and safer than 1st generation DES, providing exciting
      perspectives for the near future. A new era has started with the development of
      bio-absorbable polymers. Biodegradable polymer eluting stents, such as the
      biolimus A9 eluting stent showed non-inferiority to durable polymer sirolimus
      eluting stent and, by reducing the risk of cardiac events associated with very
      late stent thrombosis, might improve long-term clinical outcomes in a variety of
      patients including chronic stable coronary artery disease and acute coronary
      syndromes. Biodegradable polymer DES are more likely to define the 3rd generation
      DES. The goal of future development is to further increase safety and efficacy of
      DES.

PMID- 23147440
TI  - Ventricular tachycardia in "end stage" hypertrophic cardiomyopathy: a role of
      dronedarone.
AB  - Hypertrophic cardiomyopathy (HCM) occurs in 1 in every 500 individuals. It
      represents the most common cause of sudden cardiac death in those under the age
      of twenty-five. 3-5% patients with HCM go on to develop the dilated, hypokinetic
      end stage (ES) HCM with systolic failure. They have a higher incidence of heart
      failure, sudden deaths and defibrillator shocks. To the best of our knowledge
      this is first report of successful use of dronedarone for suppression of VT
      associated with ES HCM.

PMID- 23147441
TI  - Extracranial internal carotid artery stenting in Moya-Moya syndrome: a case
      report.
AB  - A 58-year-old Caucasian lady presented for severe left internal carotid artery
      (ICA) stenosis. Two months before she was operated for right carotid
      endarterectomy (CEA) in another Institution, complicated with internal carotid
      artery thrombosis and development of transient hemiplegia and aphasia.
      Postoperative selective DSA showed the development of an abnormal basal meshwork
      of collateral vessels with typical evidence for moyamoya disease. Preoperative
      workup in our Institution included cerebral MRI witch showed two ischemic right
      frontal and parietal lesions. The patient underwent successful stenting of the
      left ICA. This is the first report of extracranial ICA stenting in a patient with
      moyamoya syndrome.

PMID- 23147442
TI  - Air pollution indicators predict outbreaks of asthma exacerbations among
      elementary school children: integration of daily environmental and school health
      surveillance systems in Pennsylvania.
AB  - Objectives of this study are to determine if a relationship exists between asthma
      exacerbations among elementary school children in industrialized countries (with
      climatic seasons) and exposure to daily air pollution with particulate matter,
      sulfur dioxide, nitrogen dioxide, nitrogen oxides, carbon monoxide, and ozone,
      when controlled for potential confounders; and, if so, to derive a statistical
      model that predicts variation of asthma exacerbations among elementary school
      children. Using an ecological study design, health records of 168,25 students
      from elementary schools in 49 Pennsylvania counties employing "Health eTools for
      Schools" were analyzed. Asthma exacerbations were recorded by nurses as treatment
      given during clinic visits each day. Daily air pollution measurements were
      obtained from the EPA's air quality monitoring sites. The distribution of
      asthmatic grouping for pollen and calendar seasons was developed. A Poisson
      regression model was used to predict the number of asthma exacerbations. The
      greatest occurrence of asthma exacerbations was in autumn, followed by summer,
      spring and winter. If the number of asthma exacerbations on a day is N and the
      daily mean of asthma exacerbations for the three-year period is 48, the
      probabilities of N > 48 in tree pollen and grass pollen seasons were 56.5% and
      40.8%, respectively (p < 0.001). According to the Poisson regression, the week
      number and prior day CO, SO2, NO2, NOx, PM2.5, and O3 had significant effects on
      asthma exacerbations among students. Monitoring of air pollutants over time could
      be a reliable new means for predicting asthma exacerbations among elementary
      school children. Such predictions could help parents and school nurses implement
      effective precautionary measures.

PMID- 23147443
TI  - Evaluation of charge density and the theory for calculating membrane potential
      for a nano-composite nylon-6,6 nickel phosphate membrane.
AB  - A new crystalline organic-inorganic nano-composite nylon-6,6 nickel phosphate
      membrane was synthesised subsequent to which (a) the physico-chemical
      characteristics of the membrane were evaluated employing FTIR, SEM, EDX, TEM, XRD
      and porosity measurements, and (b) membrane potential measurements were conducted
      employing different concentrations (0.0001 <=c (M) <= 1) of KCl, NaCl and LiCl
      1:1 electrolyte solutions. The Teorell, Meyer and Sievers (TMS) theoretical
      method was employed for evaluating the charge density of the synthesised
      membranes, and the observed data were utilised to calculate membrane potentials
      using the extended TMS theory. Charge density for 1:1 electrolyte solutions was
      found to decrease in the order KCl > NaCl > LiCl, which is in accordance with a
      decrease in the size of the cation. The synthesised membrane was found to be
      cation-selective with the measured membrane potentials found to be positive in
      all instances, decreasing in the order LiCl > NaCl > KCl, which is in accordance
      with an increase in the size of the cation for the chosen electrolytes. Observed
      potential data were used to calculate the transference numbers, mobilities,
      distribution coefficients, and charge effectiveness of ions and the theoretically
      calculated potential values were found to be in good agreement with the
      experimentally observed values.

PMID- 23147444
TI  - Development of qualitative and quantitative analysis methods in pharmaceutical
      application with new selective signal excitation methods for 13 C solid-state
      nuclear magnetic resonance using 1 H T1rho relaxation time.
AB  - Most pharmaceutical drug substances and excipients in formulations exist in a
      crystalline or amorphous form, and an understanding of their state during
      manufacture and storage is critically important, particularly in formulated
      products. Carbon 13 solid-state nuclear magnetic resonance (NMR) spectroscopy is
      useful for studying the chemical and physical state of pharmaceutical solids in a
      formulated product. We developed two new selective signal excitation methods in
      (13) C solid-state NMR to extract the spectrum of a target component from such a
      mixture. These methods were based on equalization of the proton relaxation time
      in a single domain via rapid intraproton spin diffusion and the difference in
      proton spin-lattice relaxation time in the rotating frame ((1) H T1rho) of
      individual components in the mixture. Introduction of simple pulse sequences to
      one-dimensional experiments reduced data acquisition time and increased
      flexibility. We then demonstrated these methods in a commercially available drug
      and in a mixture of two saccharides, in which the (13) C signals of the target
      components were selectively excited, and showed them to be applicable to the
      quantitative analysis of individual components in solid mixtures, such as
      formulated products, polymorphic mixtures, or mixtures of crystalline and
      amorphous phases.

PMID- 23147445
TI  - Intraoperative asystole in a patient undergoing craniotomy under monitored
      anesthesia care: is it TCR?

PMID- 23147447
TI  - An unexpected cause of difficult intubation in a patient with poliomyelitis
      undergoing craniotomy.

PMID- 23147450
TI  - Arrhythmogenic right ventricular cardiomyopathy: the challenge of genetic
      interpretation in clinically suspected cases.
AB  - This is the case of a 43-year-old Caucasian man with frequent episodes of
      paroxysmal atrial fibrillation (AF) and normal resting electrocardiogram (ECG),
      who fulfilled two minor diagnostic criteria for arrhythmogenic right ventricular
      cardiomyopathy (ARVC): late potentials by signal-averaged ECG and regional right
      ventricular outflow tract (RVOT) dyskinesia with mildly dilated RVOT end
      diastolic diameter. Genetic test results revealed a disease-associated missense
      mutation in DSC2 (p.E102K), adding a major diagnostic criterion according to
      recently published modified Task Force Criteria. However, 2 years after
      successful ablative therapy for AF, the patient remains completely asymptomatic,
      without any clinical signs of ARVC. Both ventricular and supraventricular
      arrhythmias had vanished after AF ablation. Our patient mainly suffered AF
      without significant ventricular arrhythmias, a very uncommon clinical
      presentation of ARVC.

PMID- 23147449
TI  - Prognostic significance of a systemic inflammatory response in patients
      undergoing multimodality therapy for advanced colorectal cancer.
AB  - OBJECTIVES: The inflammation-based Glasgow Prognostic Score (GPS) is associated
      with outcome in a variety of cancers. This study investigated whether a modified
      GPS (mGPS) could predict survival in patients undergoing multimodality therapy
      for advanced colorectal cancer (CRC). METHODS: We enrolled 245 patients with
      advanced CRC who received chemotherapy. The mGPS was recorded prior to first-line
      chemotherapy and to cytoreductive therapy including secondary surgery and/or
      radiofrequency ablation. The prognostic significance of the mGPS was analyzed
      using Kaplan-Meier, univariate, and multivariate analyses. RESULTS: In patients
      who received chemotherapy alone (n = 163), the mGPS prior to chemotherapy was an
      independent prognostic indicator of survival [odds ratio (OR) 1.858; 95%
      confidence interval (CI) 1.213-2.846; p = 0.0044]. In patients who also underwent
      cytoreductive therapy (n = 82), the mGPS decreased after chemotherapy in 22
      patients (27%) and increased in 5 (6%). In these patients, the mGPS prior to
      cytoreductive therapy was an independent prognostic indicator of survival (OR
      3.412; 95% CI 1.198-9.720; p = 0.0216), but the mGPS prior to chemotherapy was
      not. CONCLUSIONS: The mGPS is an independent prognostic indicator of survival in
      patients undergoing multimodality therapy for advanced CRC, if recorded at a
      relevant time point.

PMID- 23147451
TI  - Alcohol consumption decreases the protection efficiency of the antioxidant
      network and increases the risk of sunburn in human skin.
AB  - In recent years, epidemiological data has demonstrated that alcohol consumption
      is a risk factor for sunburn, melanoma and nonmelanoma skin cancer. We
      hypothesized that if the concentration of the antioxidants in the skin has
      already decreased due to alcohol consumption, then an adequate neutralization of
      the free radicals induced by ultraviolet light cannot be performed. Based on this
      hypothesis, we determined the carotenoid concentration in the skin and the
      minimal erythema dose (MED) of 6 male human volunteers before and after
      consumption of alcohol or alcohol and orange juice combined. The results showed a
      significant decrease in the carotenoid concentration in the skin and the MED
      after alcohol consumption, but no significant decrease after a combined intake of
      alcohol and orange juice.

PMID- 23147454
TI  - The PLAN score: a bedside prediction rule for death and severe disability
      following acute ischemic stroke.
AB  - BACKGROUND: We sought to develop and validate a simple clinical prediction rule
      for death and severe disability after acute ischemic stroke that can be used by
      general clinicians at the time of hospital admission. METHODS: We analyzed data
      from a registry of 9847 patients (4943 in the derivation cohort and 4904 in the
      validation cohort) hospitalized with acute ischemic stroke and included in the
      Registry of the Canadian Stroke Network (July 1, 2003, to March 31, 2008; 11
      regional stroke centers in Ontario, Canada). Outcome measures were 30-day and 1
      year mortality and a modified Rankin score of 5 to 6 at discharge. RESULTS:
      Overall 30-day mortality was 11.5% (derivation cohort) and 13.5% (validation
      cohort). In the final multivariate model, we included 9 clinical variables that
      could be categorized as preadmission comorbidities (5 points for preadmission
      dependence [1.5], cancer [1.5], congestive heart failure [1.0], and atrial
      fibrillation [1.0]), level of consciousness (5 points for reduced level of
      consciousness), age (10 points, 1 point/decade), and neurologic focal deficit (5
      points for significant/total weakness of the leg [2], weakness of the arm [2],
      and aphasia or neglect [1]). Maximum score is 25. In the validation cohort, the
      PLAN score (derived from preadmission comorbidities, level of consciousness, age,
      and neurologic deficit) predicted 30-day mortality (C statistic, 0.87), death or
      severe dependence at discharge (0.88), and 1-year mortality (0.84). The PLAN
      score also predicted favorable outcome (modified Rankin score, 0-2) at discharge
      (C statistic, 0.80). CONCLUSIONS: The PLAN clinical prediction rule identifies
      patients who will have a poor outcome after hospitalization for acute ischemic
      stroke. The score comprises clinical data available at the time of admission and
      may be determined by nonspecialist clinicians. Additional studies to
      independently validate the PLAN rule in different populations and settings are
      required.

PMID- 23147456
TI  - Comparative risk for angioedema associated with the use of drugs that target the
      renin-angiotensin-aldosterone system.
AB  - BACKGROUND: Although certain drugs that target the renin- angiotensin-aldosterone
      system are linked to an increased risk for angioedema, data on their absolute and
      comparative risks are limited. We assessed the risk for angioedema associated
      with the use of angiotensin converting enzyme inhibitors (ACEIs), angiotensin
      receptor blockers (ARBs), and the direct renin inhibitor aliskiren. METHODS: We
      conducted a retrospective, observational, inception cohort study of patients 18
      years or older from 17 health plans participating in the Mini-Sentinel program
      who had initiated the use of an ACEI (n = 1 845 138), an ARB (n = 467 313),
      aliskiren (n = 4867), or a beta-blocker (n = 1 592 278) between January 1, 2001,
      and December 31, 2010. We calculated the cumulative incidence and incidence rate
      of angioedema during a maximal 365-day follow-up period. Using beta-blockers as a
      reference and a propensity score approach, we estimated the hazard ratios of
      angioedema separately for ACEIs, ARBs, and aliskiren, adjusting for age, sex,
      history of allergic reactions, diabetes mellitus, heart failure, or ischemic
      heart disease, and the use of prescription nonsteroidal anti-inflammatory drugs.
      RESULTS: A total of 4511 angioedema events (3301 for ACEIs, 288 for ARBs, 7 for
      aliskiren, and 915 for beta-blockers) were observed during the follow-up period.
      The cumulative incidences per 1000 persons were 1.79 (95% CI, 1.73-1.85) cases
      for ACEIs, 0.62 (95% CI, 0.55-0.69) cases for ARBs, 1.44 (95% CI, 0.58-2.96)
      cases for aliskiren, and 0.58 (95% CI, 0.54-0.61) cases for beta-blockers. The
      incidence rates per 1000 person-years were 4.38 (95% CI, 4.24-4.54) cases for
      ACEIs, 1.66 (95% CI, 1.47-1.86) cases for ARBs, 4.67 (95% CI, 1.88-9.63) cases
      for aliskiren, and 1.67 (95% CI, 1.56-1.78) cases for beta-blockers. Compared
      with the use of beta-blockers, the adjusted hazard ratios were 3.04 (95% CI, 2.81
      3.27) for ACEIs, 1.16 (95% CI, 1.00-1.34) for ARBs, and 2.85 (95% CI, 1.34-6.04)
      for aliskiren. CONCLUSIONS: Compared with beta-blockers, ACEIs or aliskiren was
      associated with an approximately 3-fold higher risk for angioedema, although the
      number of exposed events for aliskiren was small. The risk for angioedema was
      lower with ARBs than with ACEIs or aliskiren.

PMID- 23147455
TI  - Zonisamide for weight reduction in obese adults: a 1-year randomized controlled
      trial.
AB  - BACKGROUND: Obese individuals who have failed to achieve adequate weight loss
      with lifestyle changes have limited nonsurgical therapeutic options. We evaluated
      the efficacy and tolerability of zonisamide, an antiepileptic drug, for enhancing
      weight loss in obese patients receiving diet and lifestyle guidance. METHODS:
      This was a 1-year, randomized, double-blind, placebo-controlled trial conducted
      from January 9, 2006, through September 20, 2011, at Duke University Medical
      Center. A total of 225 obese (mean [SD] body mass index, 37.6 [4.9]) participants
      included 134 women (59.6%) and 91 men (40.4%) without diabetes mellitus. (Body
      mass index is calculated as weight in kilograms divided by height in meters
      squared.) Interventions were daily dosing with placebo (n = 74), 200 mg of
      zonisamide (n = 76), or 400 mg of zonisamide (n = 75), in addition to diet and
      lifestyle counseling by a dietitian for 1 year. Primary outcome was change in
      body weight at 1 year. RESULTS: Of the 225 randomized patients, 218 (96.9%)
      provided 1-year follow-up assessments. Change in body weight was -4.0 kg (95% CI,
      -5.8 to -2.3 kg; least squares mean, -3.7%) for placebo, -4.4 kg (-6.1 to -2.6
      kg; -3.9%; P = .79 vs placebo) for 200 mg of zonisamide, and -7.3 kg (-9.0 to 
      5.6 kg; -6.8%; P = .009 vs placebo) for 400 mg of zonisamide. In the categorical
      analysis, 23 (31.1%) assigned to placebo, 26 (34.2%; P = .72) assigned to 200 mg
      of zonisamide, and 41 (54.7%; P = .007) assigned to 400 mg of zonisamide achieved
      5% or greater weight loss; for 10% or greater weight loss, the corresponding
      numbers were 6 (8.1%), 17 (22.4%; P = .02), and 24 (32.0%; P < .001).
      Gastrointestinal, nervous system, and psychiatric adverse events occurred at a
      higher incidence with zonisamide than with placebo. CONCLUSION: Zonisamide at the
      daily dose of 400 mg moderately enhanced weight loss achieved with diet and
      lifestyle counseling but had a high incidence of adverse events. TRIAL
      REGISTRATION: clinicaltrials.gov Identifier: NCT00275834

PMID- 23147457
TI  - Telemonitoring in older adults: does one size fit all?

PMID- 23147458
TI  - Increased mortality following telemonitoring in frail elderly patients: look
      before you leap!

PMID- 23147459
TI  - Telehealth monitoring with nurse clinician oversight.

PMID- 23147461
TI  - Drug-eluting stents should not be used in ST-elevated myocardial infarction with
      cardiogenic shock.

PMID- 23147462
TI  - Translocation t(11;17) in de novo myelodysplastic syndrome not associated with
      acute myeloid or acute promyelocytic leukemia.
AB  - Translocation t(11;17) is a well-recognized variant of acute promyelocytic
      leukemia (APL) and has also been identified in patients with mixed-lineage
      leukemia (MLL) non-APL acute myeloid leukemia. Here, we describe two patients
      bearing translocation t(11;17) presenting with a clinical diagnosis of de novo
      myelodysplastic syndrome (MDS): the first with sole karyotypic abnormality
      46,XY,t(11;17)(p11.2; p13) and the second where it represented one of the two
      karyotypic abnormalities
      46,XX,del(5)(q13q33)46,XX,del(5)(q13q33),t(11;17)(q24;q23). Molecular
      characterization of both cases failed to identify fusion transcripts involving
      MLL or PLZF-RARA and no collaborating somatic mutations commonly found among MDS
      patients were seen in either case, suggesting the presence of an as yet
      unidentified oncogenic fusion protein.

PMID- 23147463
TI  - Right hepatic artery pseudoaneurysm complicating acute pancreatitis: a case
      report.
AB  - OBJECTIVE: To report a rare case of right hepatic artery pseudoaneurysm
      complicating acute pancreatitis based upon imaging findings obtained before and
      after the development of pseudoaneurysm. CLINICAL PRESENTATION AND INTERVENTION:
      A 32-year-old male with a history of acute pancreatitis 1 year prior was
      readmitted for acute pancreatitis. Computed tomography (CT) and angiography after
      admission revealed pseudoaneurysm of the right hepatic artery. Transcatheter
      arterial embolization with coils was used to successfully treat the
      pseudoaneurysm. A CT and angiography 1 year earlier did not reveal any
      pseudoaneurysm. CONCLUSION: This patient with a rare right hepatic artery
      pseudoaneurysm complicating acute pancreatitis was successfully treated with coil
      embolization.

PMID- 23147464
TI  - Electrospun eggroll-like CaSnO3 nanotubes with high lithium storage performance.
AB  - Novel eggroll-like CaSnO(3) nanotubes have been prepared by a single spinneret
      electrospinning method followed by calcination in air for the first time. The
      electrospun sample as a lithium-ion battery electrode material exhibited improved
      cycling stability and rate capability by virtue of the high surface area and
      unique hollow interior structure, compared to nanorod-structured CaSnO(3).

PMID- 23147465
TI  - Ex vivo relaxation effect of Cuscuta chinensis extract on rabbit corpus
      cavernosum.
AB  - The effect of Cuscuta chinensis extract on the rabbit penile corpus cavernosum
      (PCC) was evaluated in the present study. Penises obtained from healthy male New
      Zealand white rabbits (2.5-3.0 kg) were precontracted with phenylephrine (Phe, 10
      umol l(-1)) and then treated with various concentrations of Cuscuta chinensis
      extract (1, 2, 3, 4 and 5 mg ml(-1)). The change in penile tension was recorded,
      and cyclic nucleotides in the PCC were measured by radioimmunoassay (RIA). The
      interaction between Cuscuta chinensis and sildenafil was also evaluated. The
      result indicated that the PCC relaxation induced by Cuscuta chinensis extract was
      concentration-dependent. Pre-treatment with an nitric oxide synthase (NOS)
      inhibitor (Nomega nitro-L-arginine-methyl ester, L-NAME), a guanylyl cyclase
      inhibitor (1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one, ODQ), or a protein kinase
      A inhibitor (KT 5720) did not completely inhibit the relaxation. Incubation of
      penile cavernous tissue with the Cuscuta chinensis extract significantly
      increased cyclic guanosine monophosphate (cGMP) and cyclic adenosine
      monophosphate (cAMP) in the PCC. Moreover, the Cuscuta chinensis extract
      significantly enhanced sildenafil-induced PCC relaxation. In conclusion, the
      Cuscuta chinensis extract exerts a relaxing effect on penile cavernous tissue in
      part by activating the NO-cGMP pathway, and it may improve erectile dysfunction
      (ED), which does not completely respond to sildenafil citrate.

PMID- 23147466
TI  - Prognostic factors in Chinese patients with metastatic castration-resistant
      prostate cancer treated with docetaxel-based chemotherapy.
AB  - This study aims to evaluate the potential value of patient characteristics in
      predicting overall survival (OS) in patients with metastatic castration-resistant
      prostate cancer (mCRPC) treated with docetaxel-based thermotherapy. A total of
      115 patients with mCRPC undergoing a docetaxel q3w regimen were enrolled in this
      study. A survival analysis was performed using the Kaplan-Meier method. Cox
      proportional hazards models were used to evaluate the prognostic value of all
      covariates for OS. OS was also analysed after stratifying patients according to
      the results of multivariate analysis. The median OS for the entire cohort was
      17.0 months. The multivariate analysis showed that the prostate-specific antigen
      doubling time (PSADT), baseline haemoglobin (Hb) concentration, alkaline
      phosphatase (ALP) concentration, cycles of chemotherapy and time to castration
      resistance were independent prognostic factors of OS. According to the presence
      of PSADT <46.3 days and baseline ALP >= 110 IU l(-1), all patients were divided
      into three risk groups: low-risk group (no risk factors), intermediate-risk group
      (one risk factor) and high-risk group (two risk factors). Median OSs for patients
      in low-, intermediate- and high-risk groups were 28.0 months (95% CI: 23.8-32.2),
      21.0 months (95% CI: 18.9-23.1) and 11.0 months (95% CI: 7.6-14.4), respectively
      (P<0.001). In conclusion, PSADT, baseline Hb concentration, ALP concentration,
      cycles of chemotherapy and time to castration resistance were independent
      prognostic factors of OS in Chinese patients with mCRPC treated with docetaxel.
      PSADT combined with the baseline ALP concentration could be a useful risk
      stratification parameter for evaluating survival outcomes.

PMID- 23147467
TI  - Microsurgical varicocelectomy: a review.
AB  - Varicocelectomy is the most commonly performed surgical procedure for the
      treatment of male infertility. Although several different techniques for
      varicocele repair have been described in the literature, microsurgical
      varicocelectomy performed through a subinguinal or inguinal incision is
      recognized as the gold-standard approach for varicocelectomy, due to high success
      rates with minimal complications. Standard indications for varicocelectomy
      include palpable varicocele(s), with one or more abnormal semen parameters, and,
      for the couple trying to conceive, in the setting of normal or correctable female
      infertility. However, varicocele repair is often recommended and undertaken for
      reasons other than infertility, including low serum testosterone, testicular
      pain, testicular hypotrophy and poor sperm DNA quality. This article reviews the
      technical aspects of microsurgical varicocelectomy, and its indications in adults
      and adolescents.

PMID- 23147468
TI  - Microsurgical vasovasostomy.
AB  - Up to 6% of men who have undergone vasectomy will ultimately elect for reversal
      in the form of vasovasostomy or vasoepididymostomy for various reasons.
      Vasovasostomy performed to regain fertility is a technique that has undergone
      numerous advances during the last century, including the use of microsurgical
      equipment and principles to construct a meticulous anastomosis. It is important
      during vasovasostomy to ensure good blood supply to the anastomosis as well as to
      build as a tension-free anastomosis. Visual inspection to ensure healthy mucosa
      and inner muscularis as well as atraumatic handling of tissues is helpful. With
      vasovasostomy, it is essential to create a watertight anastomosis to prevent
      secondary scar formation. The microdot technique of vasovasostomy allows for
      markedly discrepant lumens to be brought together more precisely. Thereby, the
      planning is separated from suture placement, which prevents dog-ears and avoids
      subsequent leaks. In the age of in vitro fertilization (IVF)/intracytoplasmic
      sperm injection (ICSI), it becomes even more important to clarify outcomes after
      vasectomy reversals, as patients now have a choice between surgical sperm
      retrieval coupled with IVF/ICSI versus vasectomy reversal. Little data on long
      term outcomes for vasectomy reversals exist. Therefore, further research in this
      field needs to evaluate the rate of late failures and the predictors of late
      failures.

PMID- 23147469
TI  - [The plastic coverage of soft-tissue defects after endoprosthesis on the lower
      limb].
AB  - BACKGROUND: The implantation of endoprostheses is an established procedure in
      orthopaedic and trauma surgery. However, the techniques are often associated with
      a high risk of post-interventional infections and wound healing disorders that
      can result in loss of the prosthesis or the limb--most likely based on an
      insufficient debridement and poor soft-tissue coverage. The purpose of this study
      was to evaluate the efficacy of the coverage methods in our patient population.
      PATIENTS: In the past 10 years 38 patients with exposed knee prostheses and 14
      patients following an ankle endoprosthesis were included in this retrospective
      study over the period from 2001 to 2011. Soft-tissue reconstructions around the
      knee were mostly performed by unilateral or bilateral gastrocnemius flaps
      combined with split-skin grafts. One defect was covered with a free flap. 57% of
      the soft-tissue defects around the ankle are often problematic and were closed by
      a pedicled peroneus brevis muscle flap and 35% by a free flap (3 with a
      latissimus dorsi muscle flap, 2 with a free lateral upper arm flap and one with
      an anterolateral tight flap). RESULTS: In our patient population we achieved
      stable soft-tissue coverage in most of the cases using the above-mentioned flaps.
      Due to multiple preexisting comorbidities, it was observed that the course was
      frequently prolonged and wound healing difficulties occurred. These, however,
      could be controlled by conservative means or small secondary procedures.
      CONCLUSION: A radical debridement and an early appropriate defect coverage of the
      exposed prosthesis is crucial in the reconstruction process. Through a close
      interdisciplinary collaboration a stable soft-tissue covering can be achieved.
      Consequently it is possible to avoid a loss of the endoprosthesis, marked
      functional deficits or even amputations.

PMID- 23147470
TI  - Is red cell distribution width a marker for hypertension?.

PMID- 23147471
TI  - Negative symptoms and executive function in schizophrenia: does their
      relationship change with illness duration?
AB  - BACKGROUND: Negative symptoms and cognitive dysfunction are of crucial functional
      and prognostic importance in schizophrenia. However, the nature of the
      relationship between them and the factors that may influence it have not been
      well established. AIMS: To investigate whether the relationship between negative
      symptoms and executive function changes according to the duration of illness in
      schizophrenia. METHODS: The Positive and Negative Syndrome Scale was used to
      assess psychopathology and the Wisconsin Card Sorting Test (WCST) to evaluate
      executive function in a sample of 200 schizophrenic patients who were classified
      in 3 groups according to their duration of illness: up to 5 years (short duration
      group), 6-20 years (intermediate duration group) and over 20 years of illness
      (long duration group). RESULTS: Medium-sized correlations were found between
      negative symptoms and WCST performance as assessed by the number of completed
      categories in all 3 groups. However, differences were found according to the
      duration of schizophrenia. For patients in the short duration group, negative
      symptoms correlated with WCST nonperseverative errors, but for those in the long
      duration group the correlation was with perseverative errors. CONCLUSION: We
      found a differential relationship between negative and cognitive symptoms in
      different stages of schizophrenia. Illness duration should be considered when
      studying the relationship between negative symptoms and cognition.

PMID- 23147472
TI  - Multiple markers of hypercoagulation in patients with history of venous
      thromboembolic disease.
AB  - Markers for hypercoagulation can be used to explain why some patients may have
      had thromboembolic disease (TED). This information may then be applied to
      estimate risk for additional TED that may afflict these patients following
      subsequent surgeries. This investigation was to determine the frequency of
      hypercoagulation parameters among patients having had TED, and how frequently
      these occur in multiples. Consulting hematologists were asked to comment upon
      potential risk for recurrent TED that may be associated with additional
      surgeries. The consulting hematologist determined which laboratory tests were to
      be ordered for each patient. This retrospective study probed the hospital
      computer logs for patients having had homocysteine, protein C, factor V Leiden or
      anticardiolipin antibodies measured during a 6-year period. The laboratory
      records for patients having had any one of these tests were then examined further
      for any additional hypercoagulation laboratory studies performed. Five hundred
      and twenty patients were identified in this survey. Abnormal diagnostic results
      were found for 293 (56.3%) of these patients. Two or more abnormalities (up to 5)
      were found for 103 (35.6%) of these patients. Laboratory explanations for TED may
      be found in a large proportion of patients with TED. It is not uncommon to find
      more than one abnormality among these patients. This information may be used in
      advising patients and their physicians as to the risks of additional TED
      following future surgical procedures and can be the basis for recommending life
      style changes.

PMID- 23147473
TI  - Mean platelet volume in patients with ischemic heart disease:  meta-analysis of
      diagnostic studies.
AB  - It is now widely acknowledged that larger platelets are biologically more active
      and express a greater prothrombotic potential, but there is no definitive
      evidence on the diagnostic accuracy role of mean platelet volume (MPV) in
      patients with ischemic heart disease. We performed an electronic search for
      articles that have assessed the diagnostic accuracy of MPV in patients admitted
      at the emergency department with a suspected diagnosis of ischemic heart disease,
      including articles in which the exact number of true-positive, false-positive,
      false-negative and true-negative test results could be either directly or
      indirectly extracted. Heterogeneity was assessed by I(2) test. The cumulative
      estimates and 95% confidence interval (95% CI) of sensitivity, specificity,
      negative predictive value (NPV), positive predictive value (PPV), area under the
      receiver operator characteristic (ROC) curve (AUC) and diagnostic odds ratio
      (DOR) were calculated using a random effect model. Three studies were finally
      included in our analysis (mean quality score, 10.8) totaling 3577 participants
      (566 cases and 3011 controls). The between-study variation was high (I(2), 96.2%;
      P < 0.001). The pooled estimates were 0.820 (95% CI 0.786-0.851) for sensitivity,
      0.461 (95% CI 0.443-0.479) for specificity, 0.932 (95% CI 0.918-0.944) for NPV
      and 0.222 (95% CI 0.205-0.241) for PPV and 0.652 (95% CI 0.596-0.707) for AUC.
      The DOR was 3.9 (95% CI 2.3-6.5), with 0.52 diagnostic accuracy. The outcome of
      this meta-analysis suggests that MPV does not meet the requirements for efficient
      triage of patients in emergency department when used as stand-alone test, whereas
      its combination with high-sensitive troponin immunoassays merits further
      investigations.

PMID- 23147474
TI  - Effects of the herbicide imazapyr on juvenile Oregon spotted frogs.
AB  - Conflict between native amphibians and aquatic weed management in the Pacific
      Northwest is rarely recognized because most native stillwater-breeding amphibian
      species move upland during summer, when herbicide application to control weeds in
      aquatic habitats typically occurs. However, aquatic weed management may pose a
      risk for aquatic species present in wetlands through the summer, such as the
      Oregon spotted frog (OSF, Rana pretiosa), a state endangered species in
      Washington. Acute toxicity of herbicides used to control aquatic weeds tends to
      be low, but the direct effects of herbicide tank mixes on OSFs have remained
      unexamined. We exposed juvenile OSFs to tank mixes of the herbicide imazapyr, a
      surfactant, and a marker dye in a 96-h static-renewal test. The tank mix was
      chosen because of its low toxicity to fish and its effectiveness in aquatic weed
      control. Concentrations were those associated with low-volume (3.5 L/ha) and high
      volume (7.0 L/ha) applications of imazapyr and a clean-water control. Following
      exposure, frogs were reared for two months in clean water to identify potential
      latent effects on growth. Endpoints evaluated included feeding behavior, growth,
      and body and liver condition indices. We recorded no mortalities and found no
      significant differences for any end point between the herbicide-exposed and clean
      water control frogs. The results suggest that imazapyr use in wetland restoration
      poses a low risk of direct toxic effects on juvenile OSFs.

PMID- 23147475
TI  - First-principles simulation of the absorption bands of fluorenone in zeolite L.
AB  - The absorption spectrum of fluorenone in zeolite L is calculated from first
      principles simulations. The broadening of each band is obtained from the explicit
      treatment of the interactions between the chromophore and its environment in the
      statistical ensemble. The comparison between the simulated and measured spectra
      reveals the main factors affecting the spectrum of the chromophore in hydrated
      zeolite L. Whereas each distinguishable band is found to originate from a single
      electronic transition, the bandwidth is determined by the statistical nature of
      the environment of the fluorenone molecule. The K(+)...O=C motif is retained in
      all conformations. Although the interactions between K(+) and the fluorenone
      carbonyl group result in an average lengthening of the C[double bond, length as m
      dash]O bond and in a redshift of the lowest energy absorption band compared to
      gas phase or non-polar solvents, the magnitude of this shift is noticeably
      smaller than the total shift. An important factor affecting the shape of the band
      is fluorenone's orientation, which is strongly affected by the presence of water.
      The effect of direct interactions between fluorenone and water is, however,
      negligible.

PMID- 23147477
TI  - Anemia in heart failure: association of hepcidin levels to iron deficiency in
      stable outpatients.
AB  - BACKGROUND: Anemia is a prevalent condition in heart failure with multiple
      potential causes. The complex interaction between iron stores, hepcidin,
      inflammation and anemia is poorly comprehended. We tested the hypothesis that, in
      stable heart failure patients with anemia, hepcidin is associated with iron
      deficiency status irrespective of inflammation. METHODS AND RESULTS: Stable
      systolic heart failure outpatients with and without anemia underwent a complete
      iron panel, erythropoietin, hepcidin and tumor necrosis factor (TNF)-alpha
      assessment. Sixty outpatients were studied. Anemic patients (n = 38, mean
      hemoglobin 11.4 +/- 1 g/dl) were older (69.6 +/- 9.6 vs. 58 +/- 10.8 years old, p
      < 0.01) compared with nonanemic patients (n = 22, mean hemoglobin 13.8 +/- 1.1
      g/dl). Iron deficiency was present in 42% of patients with anemia. TNF-alpha and
      hepcidin were 29 and 21% higher in patients with anemia, respectively, compared
      to nonanemic patients; however, no correlations were found between hepcidin and
      TNF-alpha levels. Hepcidin levels in the lower tertile (<31.7 ng/ml) were
      strongly associated with iron deficiency (OR 16.5, 95% CI 2.2-121.2; p < 0.01).
      CONCLUSION: In stable heart failure patients with anemia, hepcidin levels may be
      more importantly regulated by patients' iron stores than by inflammation.

PMID- 23147476
TI  - Efficacy, safety, and survival factors for sorafenib treatment in Japanese
      patients with advanced hepatocellular carcinoma.
AB  - BACKGROUND: Sorafenib, an oral multikinase inhibitor, was approved for the
      treatment of advanced hepatocellular carcinoma (HCC), but has not been adequately
      evaluated for safety and effectiveness in Japanese patients with advanced HCC.
      AIMS: The purpose of this study was to prospectively assess the efficacy, safety,
      and risk factors for survival in patients with advanced HCC treated with
      sorafenib. METHODS: Between May 2009 and December 2010, 96 Japanese patients with
      advanced HCC (76 male, 20 female, mean age: 70.4 years) were treated with
      sorafenib. Eighty-eight patients had Child-Pugh class A, and 8 patients had Child
      Pugh class B liver cirrhosis. Barcelona Clinic Liver Cancer stage B and C were
      found in 64 and 32 patients, respectively. RESULTS: Twelve patients demonstrated
      partial response to sorafenib therapy, 43 patients had stable disease, and 33
      patients had progressive disease at the first radiologic assessment. The most
      frequent adverse events leading to discontinuation of sorafenib treatment were
      liver dysfunction (n = 8), hand-foot skin reaction (n = 7), and diarrhea (n = 4).
      The median survival time and time to progression were 11.6 and 3.2 months,
      respectively. By multivariate analysis, des-gamma-carboxy prothrombin serum
      levels and duration of treatment were identified as independent risk factors for
      survival. CONCLUSIONS: This study showed that sorafenib was safe and useful in
      Japanese patients with advanced HCC. In addition, this study demonstrated that
      sorafenib should be administered as a long-term treatment for advanced HCC
      regardless of therapeutic effect and dosage.

PMID- 23147478
TI  - Epigenetic mechanisms in psychiatry.

PMID- 23147479
TI  - Transcriptional plasticity in the brain following metabolic challenge.

PMID- 23147480
TI  - Estrogen and leptin regulation of endocrinological features of anorexia nervosa.

PMID- 23147481
TI  - Neurobiological correlates of the familial risk for stimulant drug dependence.

PMID- 23147482
TI  - Epigenetic regulation of synapsin genes in mood disorders.

PMID- 23147483
TI  - Neuroinflammation and autism: toward mechanisms and treatments.

PMID- 23147484
TI  - Cognitive training for psychiatric disorders.

PMID- 23147485
TI  - Psychoactive 'bath salts': compounds, mechanisms, and toxicities.

PMID- 23147487
TI  - Nicotine, food intake, and activation of POMC neurons.

PMID- 23147486
TI  - PACAP and the PAC1 receptor in post-traumatic stress disorder.

PMID- 23147488
TI  - Psychosis is emerging as a learning and memory disorder.

PMID- 23147489
TI  - Epigenetics of methamphetamine-induced changes in glutamate function.

PMID- 23147490
TI  - Rolling the dice: the importance of mesolimbic dopamine signaling in risky
      decision making.

PMID- 23147491
TI  - Preclinical studies shed light on individual variation in addiction
      vulnerability.

PMID- 23147492
TI  - Fractionating the impulsivity construct in adolescence.

PMID- 23147493
TI  - Proteomic analyses of PKA and AKAP signaling in cocaine addiction.

PMID- 23147494
TI  - Translational research in OCD: circuitry and mechanisms.

PMID- 23147495
TI  - Brain serotonin function in MDMA (ecstasy) users: evidence for persisting
      neurotoxicity.

PMID- 23147496
TI  - A systematic review and meta-analysis of group psychotherapy for sub-clinical
      depression in older adults.
AB  - OBJECTIVES: Studies investigating the effectiveness of group psychotherapy
      intervention in sub-threshold depression have shown varying results with
      differing effect sizes. A systematic review of randomised controlled trials of
      group psychotherapy in older adults with sub-threshold depression was conducted
      to present the best available evidence in relation to its effect on depressive
      symptomatology and the prevention of major depression. METHODS: Systematic search
      of electronic databases and random effects model for meta-analysis. RESULTS: Four
      clinical trials met the full inclusion criteria. Group cognitive behavioural
      therapy (CBT) is an effective intervention for reducing depressive symptoms in
      older adults with sub-threshold depression in comparison to waiting list.
      Computerised CBT is at least as effective as group CBT in reducing depressive
      symptoms. The benefit of group CBT at follow-up is not maintained. Group
      psychotherapy does not appear to reduce the risk of depressive disorder during
      follow-up. There are fewer drop outs from group psychotherapy when compared with
      control conditions. The methodological quality of the studies and their reporting
      are sub-optimal. CONCLUSIONS: Group psychological interventions in older adults
      with sub-threshold depression have a significant effect on depressive
      symptomatology, which is not maintained at follow-up. Group psychotherapy does
      not appear to reduce the incidence of major depressive disorders.

PMID- 23147497
TI  - Mechanism of protective effects of Danshen against iron overload-induced injury
      in mice.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Danshen (Salvia miltiorrhiza) has been widely
      prescribed in traditional folk medicine for treatment of hepatic and
      cardiovascular diseases in China and other Asian countries for several hundred
      years. MATERIALS AND METHODS: Sixty male mice were randomly divided into five
      groups: control, iron overload, low-dose Danshen (L-Danshen, 3g/kg/day), high
      dose Danshen (H-Danshen, 6g/kg/day) and deferoxamine (DFO) groups (n=12 per
      group). Iron dextran was injected intraperitoneally (i.p.) at 50mg/kg body
      weight/day to establish the iron overload model. While control mice received
      saline, mice of the treated groups simultaneously received (i.p.) injections of L
      Danshen, H-Danshen or DFO daily for 2 weeks. At the end of the experiment,
      changes in alanine aminotransferase (ALT) and aspartate aminotransferase (AST),
      glutathione peroxidase (GSH-Px), superoxide desmutase (SOD) and malondialdehyde
      (MDA) were measured, and histological changes were observed by Prussian blue or
      hematoxylin and eosin staining of the liver. Apoptosis was detected by terminal
      deoxynucleotidyl transferase mediated nick end labeling. RESULTS: Treatment of
      iron overloaded mice with either low or high doses of Danshen not only
      significantly attenuated the hepatic dysfunction (ALT/AST levels), decreased the
      content of MDA and increased the activities of GSH-Px and SOD, it also suppressed
      apoptosis in hepatocytes. Histopathological examination showed that treatment
      with Danshen reduced iron deposition and ameliorated pathological changes in the
      liver of iron overloaded mice. CONCLUSIONS: Danshen demonstrated significant
      protective effects in the liver of iron overloaded mice, which were at least
      partly due to the decrease of iron deposition and inhibition of lipid
      peroxidation and hepatocyte apoptosis.

PMID- 23147498
TI  - Sweet tea leaves extract improves leptin resistance in diet-induced obese rats.
AB  - AIM OF THE STUDY: Dietary obesity is usually characterized by leptin resistance
      and abnormal lipid metabolism. Lithocarpus polystachyus Rehd.(Sweet Tea) leaf is
      a kind of Chinese folkloric medicine, and it has been widely used for obesity,
      diabetes, and hypertension in South China. The present study is aimed at
      investigating the pharmacological mechanism of the anti-hyperleptinaemia effects
      of Sweet Tea leaves extract in high fat diet-induced obese rats. MATERIALS AND
      METHODS: We induced high fat diet obesity for 14 weeks to test the corrective
      effects of three ST doses (75, 150 and 300 mg/kg per day) for 8 weeks. At the end
      of the experiment, body weight, fasting blood glucose and serum lipids,
      superoxide dismutase (SOD), malondialdehyde (MDA), fasting serum insulin and
      leptin, C-reactive protein, adiponectin and resistin levels were measured,
      Homeostasis Model Assessment for Insulin Resistance (HOMA-IR) was also
      calculated. mRNA gene expression of PPARgamma (peroxisome proliferator-activated
      receptor gamma) and C/EBPalpha(CCAAT/enhancer-binding protein alpha) in
      epididymal adipose tissue of DIO control and experimental groups were evaluated.
      RESULTS: Sweet Tea leaves extract could significantly decrease the levels of
      serum lipids, attenuate body weight gain and lower circulating leptin and insulin
      levels, ameliorate the state of oxidative stress, raise serum adiponectin, reduce
      circulating CRP and resistin levels, and depress the expression of PPARgamma and
      C/EBPalpha in epididymal adipose tissue of obese rats. CONCLUSION: The present
      findings suggest that ST can effectively attenuate the leptin resistance at least
      through anti-hyperlipidemic activity and thus has the therapeutic potential in
      treating hyperlipidemia and hyperleptinaemia related to dietary obesity.

PMID- 23147499
TI  - Antidiabetic effects of malonyl ginsenosides from Panax ginseng on type 2
      diabetic rats induced by high-fat diet and streptozotocin.
AB  - ETHNOPHARMACOLOGY RELEVANCE: Ginseng (Panax ginseng C. A. Meyer) has been
      recorded to treat 'Xiao-ke' (emaciation and thirst) symptom in many ancient
      Chinese medical literatures (such as 'Shen Nong Ben Cao Jing') for thousands of
      years. 'Xiao-ke' symptom, in general, indicates diabetes mellitus. AIM OF THE
      STUDY: Malonyl ginsenosides (MGR) are natural ginsenosides which exist in both
      fresh and air-dried ginseng. The objective of this study is to determine the
      antidiabetic function of MGR on type 2 diabetes. MATERIALS AND METHODS: High fat
      diet-fed and streptozotocin-induced diabetic rats were treated with 50 and
      100mg/kg/d of MGR or vehicle for 3 weeks. The effects of MGR on fasting blood
      glucose (FBG), intraperitoneal glucose tolerance test (IPGTT), serum insulin
      (SI), insulin tolerance test (ITT), body weight, total cholesterol (TC), and
      triglyceride (TG) levels in type 2 diabetic rats were measured. RESULTS: After 3
      weeks of treatment, MGR administration showed significantly lower FBG levels
      compared to the diabetic control group. In glucose tolerance test, IPGTT data
      showed that both MGR 50 and 100mg/kg groups significantly increased the glucose
      disposal after glucose load. The ITT also showed improvement of insulin
      sensitivity during 120 min of insulin treatment. In addition, MGR reduced TG and
      TC contents while showed no effect on body weight in diabetic rats. CONCLUSION:
      The findings from this study suggest that MGR can alleviate hyperglycemia,
      hyperlipemia and insulin resistance of type 2 diabetes.

PMID- 23147500
TI  - The role of BCS (biopharmaceutics classification system) and BDDCS
      (biopharmaceutics drug disposition classification system) in drug development.
AB  - Biopharmaceutics Classification System and Biopharmaceutics Drug Distribution
      Classification System are complimentary, not competing, classification systems
      that aim to improve, simplify, and speed drug development. Although both systems
      are based on classifying drugs and new molecular entities into four categories
      using the same solubility criteria, they differ in the criterion for permeability
      and have different purposes. Here, the details and applications of both systems
      are reviewed with particular emphasis of their role in drug development.

PMID- 23147501
TI  - The functional neuroanatomy of odor evoked autobiographical memories cued by
      odors and words.
AB  - Behavioral evidence indicates that odor evoked autobiographical memories (OEAMs)
      are older, more emotional, less thought of and induce stronger time traveling
      characteristics than autobiographical memories (AMs) evoked by other modalities.
      The main aim of this study was to explore the neural correlates of AMs evoked by
      odors as a function of retrieval cue. Participants were screened for specific
      OEAMs and later presented with the odor cue and its verbal referent in an fMRI
      paradigm. Because the same OEAM was retrieved across both cue formats (odor and
      word), potential cue dependent brain activations were investigated. The overall
      results showed that odor and word cued OEAMs activated regions typically
      associated with recollection of autobiographical information. Although no odors
      were presented, a verbal cuing of the OEAMs activated areas associated with
      olfactory perception (e.g., piriform cortex). However, relative to word cuing, an
      odor cuing of OEAMs resulted in more activity in MTL regions such as the
      parahippocampus, and areas involved in visual vividness (e.g., occipital gyrus
      and precuneus). Furthermore, odor cues activated areas related to emotional
      processing, such as limbic and tempopolar regions significantly more. In
      contrast, word cues relative to odor cues recruited a more widespread and
      bilateral prefrontal activity. Hippocampus activity did not vary as function of
      the remoteness of the memory, but recollection of OEAMs from the 1(st) vs the
      2(nd) decade of life showed specific activation in the right OFC, whereas the
      2(nd) reflected a higher activation in the left inferior frontal gyrus.

PMID- 23147503
TI  - Decreased mRNA expression of PGC-1alpha and PGC-1alpha-regulated factors in the
      SOD1G93A ALS mouse model and in human sporadic ALS.
AB  - Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease
      characterized by selective motoneuron loss. Although the cause of ALS is unknown,
      oxidative stress, inflammation, and mitochondrial dysfunction have been
      identified as important components of its pathogenesis. Peroxisome proliferator
      activated receptor-gamma coactivator 1alpha (PGC-1alpha) plays a central role in
      the regulation of mitochondrial metabolism and biogenesis via activation of
      transcription factors, such as nuclear respiratory factors 1 and 2 and
      mitochondrial transcription factor A (Tfam). Alterations in PGC-1alpha expression
      and function have previously been described in models of Huntington and Alzheimer
      diseases. Moreover, the protective effects of PGC-1alpha have been shown in
      animal models of ALS. Levels of PGC-1alpha correlate with the number of
      acetylcholine receptor clusters in muscle. This is of particular interest because
      neurodegeneration in ALS may be a dying-back process. We investigated mRNA and
      protein expressions of PGC-1alpha and PGC-1alpha-regulated factors in the spinal
      cord and muscle tissues of SOD1 ALS mice and in ALS patients. We detected
      significant alterations in mRNA expression of PGC-1alpha and downstream factors
      with their earliest occurrence in muscle tissue. Our data provide evidence for a
      role of PGC-1alpha in mitochondrial dysfunction both in the ALS mouse model and
      in human sporadic ALS that is probably most relevant in the skeletal muscle.

PMID- 23147504
TI  - Mitochondria and peripheral neuropathies.
AB  - There has been considerable progress during the past 24 years in the molecular
      genetics of mitochondrial DNA and related nuclear DNA mutations, and more than
      100 nerve biopsies from hereditary neuropathies related to mitochondrial
      cytopathy have been accurately examined. Neuropathies were first reported in
      diseases related to point mutations of mitochondrial DNA, but they proved to be a
      prominent feature of the phenotype in mitochondrial disorders caused by defects
      in nuclear DNA, particularly in 3 genes: polymerase gamma 1 (POLG1), mitofusin 2
      (MFN2), and ganglioside-induced differentiation-associated protein 1 (GDAP1).
      Most patients have sensory-motor neuropathy, sometimes associated with
      ophthalmoplegia, ataxia, seizures, parkinsonism, myopathy, or visceral disorders.
      Some cases are caused by consanguinity, but most are sporadic with various
      phenotypes mimicking a wide range of other etiologies. Histochemistry on muscle
      biopsy, as well as identification of crystalloid inclusions at electron
      microscopy, may provide a diagnostic clue to mitochondriopathy, but nerve biopsy
      is often less informative. Nevertheless, enlarged mitochondria containing
      distorted or amputated cristae are highly suggestive, particularly when located
      in the Schwann cell cytoplasm. Also noticeable are clusters of regenerating
      myelinated fibers surrounded by concentric Schwann cell processes, and such onion
      bulb-like formations are frequently observed in neuropathies caused by GDAP1
      mutations.

PMID- 23147502
TI  - Dystroglycan on radial glia end feet is required for pial basement membrane
      integrity and columnar organization of the developing cerebral cortex.
AB  - Interactions between the embryonic pial basement membrane (PBM) and radial glia
      (RG) are essential for morphogenesis of the cerebral cortex because disrupted
      interactions cause cobblestone malformations. To elucidate the role of
      dystroglycan (DG) in PBM-RG interactions, we studied the expression of DG protein
      and Dag1 mRNA (which encodes DG protein) in developing cerebral cortex and
      analyzed cortical phenotypes in Dag1 CNS conditional mutant mice. In normal
      embryonic cortex, Dag1 mRNA was expressed in the ventricular zone, which contains
      RG nuclei, whereas DG protein was expressed at the cortical surface on RG end
      feet. Breaches of PBM continuity appeared during early neurogenesis in Dag1
      mutants. Diverse cellular elements streamed through the breaches to form
      leptomeningeal heterotopia that were confluent with the underlying residual
      cortical plate and contained variably truncated RG fibers, many types of cortical
      neurons, and radial and intermediate progenitor cells. Nevertheless, layer
      specific molecular expression seemed normal in heterotopic neurons, and axons
      projected to appropriate targets. Dendrites, however, were excessively tortuous
      and lacked radial orientation. These findings indicate that DG is required on RG
      end feet to maintain PBM integrity and suggest that cobblestone malformations
      involve disturbances of RG structure, progenitor distribution, and dendrite
      orientation, in addition to neuronal "overmigration."

PMID- 23147506
TI  - Resistance to hypoxia-induced, BNIP3-mediated cell death contributes to an
      increase in a CD133-positive cell population in human glioblastomas in vitro.
AB  - In addition to intrinsic regulatory mechanisms, brain tumor stemlike cells
      (BTSCs), a small subpopulation of malignant glial tumor-derived cells, are
      influenced by environmental factors. Previous reports showed that lowering oxygen
      tension induced an increase of BTSCs expressing CD133 and other stem cell-related
      genes and more pronounced clonogenic capacity in vitro. We investigated the
      mechanisms responsible for hypoxia-dependent induction of CD133-positive BTSCs in
      glioblastomas. We confirmed that cultures exposed to lowered oxygen levels showed
      a severalfold increase of CD133-positive BTSCs. Both the increase of CD133
      positive cells and deceleration of the growth kinetics were reversible after
      transfer to normoxic conditions. Exposure to hypoxia induced BNIP3
      (BCL2/adenovirus E1B 19-kDa protein-interacting protein 3)-dependent apoptosis
      preferentially in CD133-negative cells. In contrast, CD133-positive cells proved
      to be more resistant to hypoxia-induced programmed cell death. Application of the
      demethylating agent 5'-azacitidine resulted in an increase of BNIP3 expression
      levels in CD133-positive cells. Thus, epigenetic modifications led to their
      better survival in lowered oxygen tension. Moreover, the, hypoxia-induced
      increase of CD133-positive cells was inhibited after 5'-azacitidine treatment.
      These results suggest the possible efficacy of a novel therapy for glioblastoma
      focused on eradication of BTSCs by modifications of epigenetic regulation of gene
      expression.

PMID- 23147505
TI  - Digital pathology and image analysis for robust high-throughput quantitative
      assessment of Alzheimer disease neuropathologic changes.
AB  - Quantitative neuropathologic methods provide information that is important for
      both research and clinical applications. The technologic advancement of digital
      pathology and image analysis offers new solutions to enable valid quantification
      of pathologic severity that is reproducible between raters regardless of
      experience. Using an Aperio ScanScope XT and its accompanying image analysis
      software, we designed algorithms for quantitation of amyloid and tau pathologies
      on 65 beta-amyloid (6F/3D antibody) and 48 phospho-tau (PHF-1)-immunostained
      sections of human temporal neocortex. Quantitative digital pathologic data were
      compared with manual pathology counts. There were excellent correlations between
      manually counted and digitally analyzed neuropathologic parameters (R2 = 0.56
      0.72). Data were highly reproducible among 3 participants with varying degrees of
      expertise in neuropathology (intraclass correlation coefficient values, >0.910).
      Digital quantification also provided additional parameters, including average
      plaque area, which shows statistically significant differences when samples are
      stratified according to apolipoprotein E allele status (average plaque area,
      380.9 MUm2 in apolipoprotein E [Latin Small Letter Open E]4 carriers vs 274.4
      MUm2 for noncarriers; p < 0.001). Thus, digital pathology offers a rigorous and
      reproducible method for quantifying Alzheimer disease neuropathologic changes and
      may provide additional insights into morphologic characteristics that were
      previously more challenging to assess because of technical limitations.

PMID- 23147507
TI  - A quantitative postmortem MRI design sensitive to white matter hyperintensity
      differences and their relationship with underlying pathology.
AB  - White matter hyperintensities (WMHs) associate with both cognitive slowing and
      motor dysfunction in the neurologically normal elderly. A full understanding of
      the pathology underlying this clinicoradiologic finding is currently lacking in
      autopsy-confirmed normal brains. To determine the histopathologic basis of WMH
      seen on magnetic resonance imaging, we studied the relationship between
      postmortem fluid-attenuated inversion recovery (FLAIR) intensity and
      neuropathologic markers of WM lesions (WMLs) that correspond to WMH in
      cognitively normal aging brains. Samples of periventricular (n = 24), subcortical
      (n = 26), and normal-appearing WM (NAWM, n = 31) from 4clinically and
      pathologically confirmed normal cases were examined. The FLAIR intensity,
      vacuolation, and myelin basic protein immunoreactivity loss were significantly
      higher in periventricular WML versus subcortical WML; both were higher than in
      NAWM. The subcortical WML and NAWM had significantly less axonal loss, astrocytic
      burden, microglial density, and oligodendrocyte loss than those of the
      periventricular WML. Thus, vacuolation, myelin density, and small vessel density
      contribute to the rarefaction of WM, whereas axonal density, oligodendrocyte
      density, astroglial burden, and microglial density did not. These data suggest
      that the age-related loss of myelin basic protein and the decrease in small
      vessel density may contribute to vacuolation of WM. Vacuolation enables
      interstitial fluid to accumulate, which contributes to the prolonged T2
      relaxation and elevated FLAIR intensity in the WM.

PMID- 23147508
TI  - Brain-derived neurotrophic factor-transfected and nontransfected 3T3 fibroblasts
      enhance migratory neuroblasts and functional restoration in mice with
      intracerebral hemorrhage.
AB  - Neurogenesis via the activation of endogenous neural progenitor cells is a
      potential treatment strategy for brain injury, including intracerebral hemorrhage
      (ICH). We assessed the efficacy of combined cell and brain-derived neurotrophic
      factor (BDNF) treatment in a mouse model of ICH induced by intracerebral
      collagenase injection. Complementary DNAs of mouse BDNF were transfected into
      cell lines of 3T3 fibroblasts. The expression and bioactivity of BDNF were
      analyzed by immunocytochemistry, Western blot, ELISA, and functional assays.
      Hematoma area and brain tissue loss were assessed by magnetic resonance imaging.
      The BDNF-transfected or nontransfected 3T3 fibroblasts were implanted as a growth
      factor source in mice with ICH. Neurogenesis and functional recovery were
      evaluated 15 days after ICH. The BDNF-treated mice had the most doublecortin
      positive cells near lesions and the least brain tissue loss in all groups. Both
      cell treatment groups had abundant newly proliferative glial fibrillary acidic
      protein-positive cells and better functional improvement than controls. These
      results indicate that fibroblast transplantation, together with recombinant BDNF
      treatment, after ICH is beneficial in mice. The early functional recovery may
      result from the growth factors that are provided or evoked by the implanted
      grafts. These results suggest a potential approach for combining gene and cell
      therapy for ICH treatment.

PMID- 23147509
TI  - Post-insult ibuprofen treatment attenuates damage to the serotonergic system
      after hypoxia-ischemia in the immature rat brain.
AB  - There is currently no therapeutic intervention to stem neonatal brain injury
      after exposure to hypoxia-ischemia (HI). Potential neuroprotective treatments
      that can be delivered postinsult that target neuroinflammation and are safe to
      use in neonates are attractive. One candidate is ibuprofen. Ibuprofen is a
      nonsteroidal anti-inflammatory drug that inhibits cyclooxygenase enzymes and is
      used in neonates to treat patent ductus arteriosus. We investigated whether
      ibuprofen can inhibit neuroinflammation and attenuate neuronal damage manifested
      in a rodent model of preterm HI. Postnatal day 3 (P3) rat pups were subjected to
      HI (right carotid artery ligation, 30 minutes 6% O2). Ibuprofen was then
      administered daily for 1 week (100 mg/kg P3 2 hours after HI, 50 mg/kg P4-P9;
      subcutaneously). Ibuprofen treatment prevented the P3 HI-induced reductions in
      brain serotonin levels, serotonin transporter expression, and numbers of
      serotonergic neurons in the dorsal raphe nuclei on P10. Ibuprofen also
      significantly attenuated P3 HI-induced increases in brain cyclooxygenase 2
      protein expression, interleukin-1beta, and tumor necrosis factor levels, as well
      as the increase in numbers of activated microglia. Thus, ibuprofen administered
      after an HI insult may be an effective pharmacologic intervention to reduce HI
      induced neuronal brain injury in the preterm neonate by limiting the effects of
      neuroinflammatory mediators.

PMID- 23147511
TI  - Does antiviral therapy prevent recurrence of hepatitis B virus-related
      hepatocellular carcinoma after curative liver resection?

PMID- 23147510
TI  - Gene dosage-dependent association of DYRK1A with the cytoskeleton in the brain
      and lymphocytes of down syndrome patients.
AB  - The triplication of the DYRK1A gene encoding proline-directed serine/threonine
      kinase and located in the critical region of Down syndrome (DS) has been
      implicated in cognitive deficits and intellectual disability of individuals with
      DS. We investigated the effect of abnormal levels of this kinase on the
      cytoskeleton in brain and peripheral tissues of DS subjects. In DS tissues, the
      predictable approximately equal to 1.5-fold enhancement of the levels of DYRK1A
      protein was demonstrated. An association of DYRK1A with all 3 major cytoskeleton
      networks was identified using immunoprecipitation. We concentrated on the actin
      cytoskeleton because its association with DYRK1A was the most affected by the
      enzyme levels. As measured by coimmunoprecipitation in DS tissues, but not in
      fragile X lymphocytes, actin association with DYRK1A was reduced. This reduced
      association was dependent on the state of phosphorylation of cytoskeletal
      proteins and was present only in cells overproducing DYRK1A kinase; therefore,
      the effect was attributable to the DYRK1A gene dosage. Alterations of DYRK1A
      actin assemblies were detected in newborn and infant groups, thereby linking
      DYRK1A overexpression with abnormal brain development of DS children. The
      identification of the actin cytoskeleton as one of cellular targets of DYRK1A
      action provides new insights into a gene dosage-sensitive mechanism by which
      DYRK1A could contribute to the pathogenesis of DS. In addition, the presence of
      this DS-specific cytoskeleton anomaly in lymphocytes attests to the systemic
      nature of some features of DS. To our knowledge, this is the first study
      conducted in human tissue that shows DYRK1A association with the cytoskeleton.

PMID- 23147512
TI  - Outbreak of fungemia caused by Candida parapsilosis in a neonatal intensive care
      unit: molecular investigation through microsatellite analysis.
AB  - BACKGROUND: Opportunistic infections are an increasingly common problem in
      hospitals, and the yeast Candida parapsilosis has emerged as an important
      nosocomial pathogen, especially in neonatal intensive care units (NICUs) where it
      has been responsible for outbreak cases. Risk factors for C. parapsilosis
      infection in neonates include prematurity, very low birth weight, prolonged
      hospitalization, indwelling central venous catheters, hyperalimentation,
      intravenous fatty emulsions and broad spectrum antibiotic therapy. Molecular
      methods are widely used to elucidate these hospital outbreaks, establishing
      genetic variations among strains of yeast. AIMS: The aim of this study was to
      detect an outbreak of C. parapsilosis in an NICU at the "Hospital das Clinicas",
      Faculty of Medicine of Botucatu, a tertiary hospital located in Sao Paulo,
      Brazil, using the molecular genotyping by the microsatellite markers analysis.
      METHODS: A total of 11 cases of fungemia caused by C. parapsilosis were
      identified during a period of 43 days in the NICU. To confirm the outbreak all
      strains were molecularly typed using the technique of microsatellites. RESULTS:
      Out of the 11 yeast samples studied, nine showed the same genotypic profile using
      the technique of microsatellites. CONCLUSIONS: Our study shows that the technique
      of microsatellites can be useful for these purposes. In conclusion, we detected
      the presence of an outbreak of C. parapsilosis in the NICU of the hospital
      analyzed, emphasizing the importance of using molecular tools, for the early
      detection of hospital outbreaks, and for the introduction of effective preventive
      measures, especially in NICUs.

PMID- 23147513
TI  - Preservation of Agaricus subrufescens strains at low temperature by using
      cultures on sorghum grains.
AB  - BACKGROUND: One of the main problems for the preservation of genetics resources
      of Agaricus subrufescens is to maintain the viability of the strains because the
      mycelium is very sensitive to cooling and therefore it ages rapidly. AIMS:
      Evaluate the viability of A. subrufescens strains stored as cultures on sorghum
      grain (spawn) at different temperatures. METHODS: Eighteen strains of A.
      subrufescens and three strains of Agaricus bisporus were studied. Spawn's
      viability was evaluated under the following conditions: (1) control at 25 degrees
      C (C), (2) cooling to 4 degrees C (R) and (3) freezing in liquid nitrogen at -196
      degrees C (LN). Samples were recovered from week 4 every 2 weeks until week 12
      and week 24 in C and R, whereas in LN samples were recovered at 4, 12 and 24
      weeks. Viability was evaluated in 50 seeds, by strain and condition, recovering
      the mycelium in Petri dishes with potato dextrose agar medium (PDA). Mycelium
      growth was also evaluated on PDA after 14 days of recovery. RESULTS: Most strains
      showed 100% viability and they were recovered usually in 1 day. In LN the
      viability ranged between 84 and 100% depending on the strain, but in some cases
      recovery took more than 10 days. Mycelial growth decreased gradually over time
      and although the results show significant differences between treatments C and R,
      the decline is associated with ageing of the mycelium rather than the treatment
      itself. CONCLUSIONS: Culture on sorghum grain and storage at low temperature is
      an interesting way to preserve genetic resources of A. subrufescens.

PMID- 23147514
TI  - Dermatomycosis in lower limbs of diabetic patients followed by podiatry
      consultation.
AB  - BACKGROUND: Diabetic patients are particularly susceptible to fungal infections
      due to modifications that occur in their immunological system. These
      modifications compromise natural defences, such as skin and nails, especially
      from lower limbs. AIMS: Assessing the presence of dermatomycosis in lower limbs
      of Portuguese diabetic patients followed on Podiatry consultation. Determination
      of possible predisposing factors and the most frequent fungal species associated
      with the cases are included in the study. METHODS: A six-month prospective study
      was carried out in 163 diabetic patients with signs and symptoms of
      dermatomycosis followed by Podiatry at the Portuguese Diabetes Association in
      Lisbon. Samples from the skin and/or nails of the lower limbs were collected and
      demographic and clinical data of those patients were recorded. RESULTS:
      Trichophyton rubrum was the most frequently isolated dermatophyte (12.1%),
      followed by Trichophyton mentagrophytes (7.7%) and Trichophyton tonsurans (4.4%).
      Our study showed positive associations between type 2 diabetes and the presence
      of dermatomycosis in the studied population (p=0.013); this association was also
      shown between the occurrence of dermatomycosis and the localization of the body
      lesion (p=0.000). No other predisposing factor tested was positively associated
      with infection (p>0.05). CONCLUSIONS: Data on superficial fungal infections in
      diabetic patients are scarce in Portugal. This study provides information on the
      characterization of dermatomycosis in lower limbs of diabetic patients.

PMID- 23147515
TI  - Exogenous glutamate modulates porcine retinal development in vitro.
AB  - Embryogenesis of the retina is a complex event orchestrated by a multitude of
      physical and biochemical signals. To study the impact of intrinsic developmental
      cues, the retinal tissue can be isolated in culture which also enables modulation
      of normal development for other purposes, i.e. transplantation of specific
      neuronal cell types. In the present experiment, cell type development of immature
      porcine retinal tissue kept in culture was explored using specific
      immunohistochemical markers. Retinal explants were either kept under standard
      culture conditions or supplemented with glutamate and their morphology was
      compared with in vivo controls of corresponding age. After 15 days in vitro
      (DIV), E45 retinal explants displayed several signs of atypical development when
      compared with E60 in vivo controls. First, an accelerated photoreceptor
      differentiation was evident, seen in sections labeled with antibodies directed
      against recoverin, rhodopsin and synaptophysin. Second, apoptotic cells in the
      inner retina were more prevalent in the cultured retinas (TUNEL). Rod
      photoreceptor differentiation as well as inner retinal apoptosis was even more
      pronounced in glutamate-supplemented specimens in which they occurred already at
      8 DIV. Muller cell, vimentin and GFAP expression was not affected in any of the
      cultured retinas. These results suggest that normal retinal embryogenesis is more
      dependent on tissue extrinsic factors than what has been deduced from previous
      small animal experiments. Glutamate, which has been identified as an important
      regulator of cell cycle exit, may also be important for photoreceptor
      differentiation and induction of developmental apoptosis. Insights into retinal
      cell type differentiation under in vitro conditions is of interest from a
      biological standpoint, and the possibility of modulation of this process is
      valuable for research directed towards cell replacement in retinal degenerative
      disease.

PMID- 23147516
TI  - Taming the germyliumylidene [CIGe:]+ and germathionium [CIGe=S]+ ions by donor
      acceptor stabilization using 1,8-bis(tributylphosphazenyl)naphthalene.
AB  - The novel chlorogermyliumylidene complex L[ClGe:](+) (L = 1,8-bis(tri-n
      butylphosphanzenyl)naphthalene) with a 'naked' Cl(-) as a counter anion was
      synthesized through reaction of L with Cl(2)Ge: and fully characterized. Its
      reaction with elemental sulfur afforded the first germathionium [ClGe=S](+)
      cation containing species. The latter has also been fully characterized,
      including single-crystal X-ray diffraction analysis.

PMID- 23147517
TI  - Generation of hypoallergenic neoglycoconjugates for dendritic cell targeted
      vaccination: a novel tool for specific immunotherapy.
AB  - The incidence of allergic disorders and asthma continuously increased over the
      past decades, consuming a considerable proportion of the health care budget.
      Allergen-specific subcutaneous immunotherapy represents the only intervention
      treating the underlying causes of type I allergies, but still suffers from
      unwanted side effects and low compliance. There is an urgent need for novel
      approaches improving safety and efficacy of this therapy. In the present study we
      investigated carbohydrate-mediated targeting of allergens to dermal antigen
      presenting cells and its influence on immunogenicity and allergenicity. Mannan,
      high (40kDa) and low (6kDa) molecular weight dextran, and maltodextrin were
      covalently attached to ovalbumin and papain via mild carbohydrate oxidation
      resulting in neoglycocomplexes of various sizes. In particular, mannan-conjugates
      were efficiently taken up by dendritic cells in vivo leading to elevated humoral
      immune responses against the protein moiety and a shift from IgE to IgG. Beyond
      providing an adjuvant effect, papain glycocomplexes also proved to mask B-cell
      epitopes, thus rendering the allergen derivative hypoallergenic. The present data
      demonstrate that carbohydrate-modified allergens combine targeting of antigen
      presenting cells with hypoallergenicity, offering the potential for low dose
      allergen-specific immunotherapy while concomitantly reducing the risk of side
      effects.

PMID- 23147518
TI  - Cardiovascular risk factors and systemic endothelial function in patients with
      cirrhosis.
AB  - OBJECTIVES: Cardiovascular risk factors (CVRF) lead to systemic endothelial
      dysfunction. It has been suggested that in cirrhosis, cardiovascular risk is low
      and systemic endothelial function is enhanced. However, there is no prospective
      study evaluating the relationship between cardiovascular risk and systemic
      endothelial function in cirrhosis, which was investigated here. METHODS: In 47
      patients with cirrhosis (33 males; median Child-Pugh score 8; median age 55
      years), we evaluated: laboratory parameters, hepatic and systemic hemodynamics,
      CVRF, 10-year global cardiovascular risk by Framingham score, and presence of
      carotid plaques. Systemic endothelial dysfunction was investigated non-invasively
      by flow-mediated dilatation (FMD) of the brachial artery by ultrasound and
      defined as FMD <10%. RESULTS: Cardiovascular risk (median 7%) was low in 25%,
      moderate in 26%, moderately high in 40%, and high in 9%. Fifty-three percent of
      patients had systemic endothelial dysfunction. Systemic endothelial dysfunction
      (low FMD) increased in parallel with CV risk (linear trend P=0.039) and was
      higher in patients overweight or obese. Conversely, FMD increased in parallel
      with Child-Pugh/Mayo Clinic Model for End-stage Liver Disease (MELD) score,
      bilirubin, serum sodium, plasma renin activity, leukocyte count, platelet count,
      and with lower arterial pressure, suggesting that enhanced FMD is a feature of
      advanced liver failure and inflammation. Cardiovascular risk, bilirubin,
      leukocyte count, and arterial pressure remained independently associated with
      systemic endothelial dysfunction. CONCLUSIONS: CV risk was not low in our studied
      patients with cirrhosis, and systemic endothelial dysfunction was frequent in
      this population. In cirrhosis, similar to general population, cardiovascular risk
      impaired systemic FMD, although liver failure attenuated endothelial dysfunction.

PMID- 23147519
TI  - Abdominal and total adiposity and the risk of acute pancreatitis: a population
      based prospective cohort study.
AB  - OBJECTIVES: Previous research has indicated that obesity may be linked to the
      severity of acute pancreatitis. However, the association between abdominal and
      total adiposity as risk factors in the development of acute pancreatitis in a
      general population has not been studied. METHODS: A follow-up study was
      conducted, using the Swedish Mammography Cohort and the Cohort of Swedish Men, to
      examine the association between waist circumference and body mass index (BMI) and
      the risk of first-time acute pancreatitis. Severe acute pancreatitis was defined
      as hospital stay of >14 days, in-hospital death, or mortality within 30 days of
      discharge. Cox proportional hazards models were used to estimate rate ratios
      (RRs) with 95% confidence intervals (CIs), adjusted for confounders. RESULTS: In
      total, 68,158 individuals, aged 46-84 years, were studied for a median of 12
      years. During this time, 424 persons developed first-time acute pancreatitis. The
      risk of acute pancreatitis among those with a waist circumference of >105 cm was
      twofold increased (RR=2.37; 95% CI: 1.50-3.74) compared with individuals with a
      waist circumference of 75.1-85.0 cm, when adjusted for confounders. This
      association was seen in patients with non-gallstone-related and gallstone-related
      acute pancreatitis. The results remained unchanged when stratifying the analyses
      with regards to sex or the severity of acute pancreatitis. There was no
      association between BMI and the risk of acute pancreatitis. CONCLUSIONS:
      Abdominal adiposity, but not total adiposity, is an independent risk factor for
      the development of acute pancreatitis.

PMID- 23147520
TI  - Acid-suppressive therapy with esomeprazole for relief of unexplained chest pain
      in primary care: a randomized, double-blind, placebo-controlled trial.
AB  - OBJECTIVES: High-quality data regarding the efficacy of acid-suppressive
      treatment for unexplained chest pain are lacking. The aim of this study was to
      evaluate the efficacy of esomeprazole in primary-care treatment of patients with
      unexplained chest pain stratified for frequency of reflux/regurgitation symptoms.
      METHODS: Patients with a >= 2-week history of unexplained chest pain (unrelated
      to gastroesophageal reflux) who had at least moderate pain on >= 2 of the last 7
      days were stratified by heartburn/regurgitation frequency (<= 1 day/week (stratum
      1) vs. >= 2 days/week (stratum 2)) and randomized to 4 weeks of double-blind
      treatment with twice-daily esomeprazole 40 mg or placebo. Chest pain relief
      during the last 7 days of treatment (<= 1 day with minimal symptoms assessed
      daily using a 7-point scale) was analyzed by stratum in keeping with the
      predetermined analysis plan. RESULTS: Overall, 599 patients (esomeprazole: 297,
      placebo: 302) were randomized. In stratum 1, more esomeprazole than placebo
      recipients achieved chest pain relief (38.7% vs. 25.5%; P=0.018); no between
      treatment difference was observed in stratum 2 (27.2% vs. 24.2%; P=0.54).
      However, esomeprazole was superior to placebo in a post-hoc analysis of the whole
      study population (combined strata; 33.1% vs. 24.9%; P=0.035). CONCLUSIONS: A 4
      week course of high-dose esomeprazole provided statistically significant relief
      of unexplained chest pain in primary-care patients who experienced infrequent or
      no heartburn/regurgitation, but there was no such significant reduction in
      patients with more frequent reflux symptoms.

PMID- 23147522
TI  - Sedation in screening colonoscopy: impact on quality indicators and
      complications.
AB  - OBJECTIVES: Quality indicators including cecal intubation rate (CIR) and adenoma
      detection rate (ADR) are established. Sex differences of quality indicators are
      observed, but the influence of sedation has not been investigated so far. The
      objective of this study is to assess the impact of sedation on quality
      indicators, including CIR and ADR, according to sex. METHODS: We analyzed data of
      52,506 screening colonoscopies performed by 196 endoscopists between November
      2007 and April 2011 according to the Austrian "quality management for colon
      cancer prevention" program. RESULTS: Sedation did not affect polyp detection rate
      (women P=0.7972, men P=0.3711) or ADR for both sexes (women P=0.2773, men
      P=0.8676). ADR was not significantly influenced by sedation (P=0.1272), but by
      age and sex (both P<0.0001), when the executing endoscopist was considered.
      Although women were more often sedated than men (90.70 vs. 81.83%; P<0.0001), CIR
      was slightly lower in women than in men (94.69 vs. 96.58%; P<0.0001). Sedation
      improved the CIR in women by 2.95% (94.96 vs. 92.01%; P<0.0001), whereas in men
      it was just by 1.28% (96.81 vs. 95.53%; P<0.0001). Sedated women only reached the
      CIR of unsedated men (94.96 vs. 95.53%; P=0.1005). Accounting for the intra
      observer influence of the endoscopist, the overall CIR was influenced by the
      interaction of sex and age (P=0.0049), but not by sedation (P=0.1435).
      CONCLUSIONS: Sedation does not increase adenoma or polyp detection, although it
      leads to an increase in CIR in men and women. This effect is more pronounced in
      women, yet CIR of men remains higher compared with women. Quality indicators are
      mainly influenced by the patient's age, sex, and the endoscopists' individual
      performance, rather than the endoscopists' subspeciality or procedural
      experience.

PMID- 23147523
TI  - Prognostic value of serologic and histologic markers on clinical relapse in
      ulcerative colitis patients with mucosal healing.
AB  - OBJECTIVES: Endoscopic mucosal healing is a key endpoint for the treatment of
      ulcerative colitis (UC). The role of microscopic activity in predicting disease
      relapse has not been fully assessed. We aimed to investigate the predictive role
      of serologic and histologic markers on disease relapse in UC patients with
      endoscopically inactive disease. METHODS: Adult UC patients with endoscopically
      inactive disease (Mayo 0) and a 12-month follow-up between 2008 and 2011 were
      retrospectively included. An expert pathologist evaluated all colonic biopsies
      for histologic activity (Geboes score) and the presence of basal plasmacytosis.
      Blood samples collected around the time of endoscopy were analyzed. Disease
      relapse, defined as a clinical Mayo score >=3, was documented during follow-up.
      RESULTS: The study cohort consisted of 75 patients (53% men, median age 47
      years). Despite normal endoscopy, histology showed inflammatory activity with a
      Geboes score >=3.1 in 40% and basal plasmacytosis in 21% of patients. At 12
      months, clinical relapse was observed in 20% (n=15) of patients. Presence of
      basal plasmacytosis (P=0.007) and a Geboes score >=3.1 (P=0.007) were predictive
      of disease relapse. Using multivariate analysis, the presence of basal
      plasmacytosis was predictive of clinical relapse (odds ratio (OR) 5.13 (95%
      confidence interval (CI): 1.32-19.99), P=0.019), whereas the use of biologicals
      at endoscopy favored remission (OR 0.24 (95% CI: 0.05-1.01), P=0.052).
      CONCLUSIONS: We demonstrated that the presence of basal plasmacytosis predicts UC
      clinical relapse in patients with complete mucosal healing. We recommend closer
      follow-up and optimization of medical therapy in patients with basal
      plasmacytosis.

PMID- 23147524
TI  - Helicobacter pylori-negative gastritis: prevalence and risk factors.
AB  - OBJECTIVES: Recent studies using histology alone in select patients have
      suggested that Helicobacter pylori-negative gastritis may be common. The
      objective of this study was to investigate the prevalence of H. pylori among
      individuals with histologic gastritis. METHODS: Subjects between 40 and 80 years
      underwent elective esophagogastroduodenoscopy at a VA Medical Center. Gastric
      biopsies were mapped from seven prespecified sites (two antrum, four corpus, and
      one cardia) and graded by two gastrointestinal pathologists, using the Updated
      Sydney System. H. pylori-negative required four criteria: negative triple
      staining at all seven gastric sites, negative H. pylori culture, negative IgG H.
      pylori serology, and no previous treatment for H. pylori. Data regarding tobacco
      smoking, alcohol drinking, nonsteroidal anti-inflammatory drug, and proton pump
      inhibitor (PPI) use were obtained by questionnaire. RESULTS: Of the 491
      individuals enrolled, 40.7% (200) had gastritis of at least grade 2 in at least
      one biopsy site or grade 1 in at least two sites. Forty-one (20.5%) had H. pylori
      negative gastritis; most (30 or 73.2%) had chronic gastritis, five (12.2%) had
      active gastritis, and six (14.6%) had both. H. pylori-negative gastritis was
      approximately equally distributed in the antrum, corpus, and both antrum and
      corpus. Past and current PPI use was more frequent in H. pylori-negative vs. H.
      pylori-positive gastritis (68.2% and 53.8%; P=0.06). CONCLUSIONS: We used
      multiple methods to define non-H. pylori gastritis and found it in 21% of
      patients with histologic gastritis. While PPI use is a potential risk factor, the
      cause or implications of this entity are not known.

PMID- 23147521
TI  - Clinical guideline: management of gastroparesis.
AB  - This guideline presents recommendations for the evaluation and management of
      patients with gastroparesis. Gastroparesis is identified in clinical practice
      through the recognition of the clinical symptoms and documentation of delayed
      gastric emptying. Symptoms from gastroparesis include nausea, vomiting, early
      satiety, postprandial fullness, bloating, and upper abdominal pain. Management of
      gastroparesis should include assessment and correction of nutritional state,
      relief of symptoms, improvement of gastric emptying and, in diabetics, glycemic
      control. Patient nutritional state should be managed by oral dietary
      modifications. If oral intake is not adequate, then enteral nutrition via
      jejunostomy tube needs to be considered. Parenteral nutrition is rarely required
      when hydration and nutritional state cannot be maintained. Medical treatment
      entails use of prokinetic and antiemetic therapies. Current approved treatment
      options, including metoclopramide and gastric electrical stimulation (GES,
      approved on a humanitarian device exemption), do not adequately address clinical
      need. Antiemetics have not been specifically tested in gastroparesis, but they
      may relieve nausea and vomiting. Other medications aimed at symptom relief
      include unapproved medications or off-label indications, and include domperidone,
      erythromycin (primarily over a short term), and centrally acting antidepressants
      used as symptom modulators. GES may relieve symptoms, including weekly vomiting
      frequency, and the need for nutritional supplementation, based on open-label
      studies. Second-line approaches include venting gastrostomy or feeding
      jejunostomy; intrapyloric botulinum toxin injection was not effective in
      randomized controlled trials. Most of these treatments are based on open-label
      treatment trials and small numbers. Partial gastrectomy and pyloroplasty should
      be used rarely, only in carefully selected patients. Attention should be given to
      the development of new effective therapies for symptomatic control.

PMID- 23147527
TI  - Facile synthesis of p-type Cu2O/n-type ZnO nano-heterojunctions with novel
      photoluminescence properties, enhanced field emission and photocatalytic
      activities.
AB  - Two kinds of Cu(2)O-ZnO nano-heteroarchitectures were fabricated through a
      hydrothermal method. By utilizing polyethyleneimine (PEI) as a binding agent, ZnO
      nanoparticles were uniformly self-assembled onto Cu(2)O micro structures.
      Photoluminescence (PL), field emission and photocatalytic activities of the
      composite samples were investigated and compared with those of the pure Cu(2)O
      samples. The results reveal that ZnO nanoparticles combined on Cu(2)O
      microstructures remarkably changed the PL signals, and significantly enhanced the
      field emission and photocatalytic activities. The novel PL properties, enhanced
      field emission and photocatalysis activities are attributed to the electron
      transition and the inhibition of photo-induced electron-hole pairs recombination,
      which stem from interfacial defect states and energy band differentials at the
      interface of Cu(2)O and ZnO. The surface nano-protrusions, large surface area and
      better dye adsorption induced by ZnO nanoparticles are responsible for the field
      emission and photocatalysis improvements as well.

PMID- 23147526
TI  - Large animal model for osteoporosis in humans: the ewe.
AB  - Osteoporosis is a chronic systemic disease characterised by bone loss and
      microarchitectural deterioration. Since the underlying regulatory mechanisms are
      still not fully understood and treatment options are not satisfactorily resolved,
      massive efforts are underway to further investigate this critical illness. Large
      animal models are stipulated, e.g. by the Food and Drug Administration, for
      preclinical prevention and intervention studies related to osteoporosis research;
      in this context, the ewe has already proven its value for orthopaedic research.
      Although oestrogen deficiency doubtless influences bone metabolism in sheep, the
      ovariectomised ewe seems unsuitable as a model for postmenopausal osteoporosis
      and bone loss induction due to its unreliable impact on bone mass and structure.
      In contrast, glucocorticoid treatment has a major impact on bone turnover and
      leads to bone conditions comparable to those found in steroid-treated humans.
      However, adverse side effects can be dramatic resulting in unacceptable
      discomfort and illness of the experimental animals. Further improvements are
      therefore essential to judge this model as ethically appropriate. Additionally,
      models for osteoporosis induced by surgical interventions of central regulatory
      mechanisms seem to be attractive, as remarkable bone loss is induced by only one
      surgical procedure without any further treatment. Taken together, different ewe
      models for osteoporosis have been successfully established and are invaluable for
      orthopaedic research. However, the search for a 'perfect' large remodelling
      animal model - in terms of mimicking the human disease and compatibility of bone
      loss, and without ethical concerns - is still on-going.

PMID- 23147525
TI  - Impact of antibodies to infliximab on clinical outcomes and serum infliximab
      levels in patients with inflammatory bowel disease (IBD): a meta-analysis.
AB  - OBJECTIVES: Antibodies to infliximab (ATIs) have been associated with loss of
      clinical response and lower serum infliximab (IFX) levels in some studies of
      patients with inflammatory bowel disease (IBD). This has important implications
      for patient management and development of novel biologic therapies. The objective
      of this study was to perform a systematic review and meta-analysis of studies
      that reported clinical outcomes and IFX levels according to patients' ATI status.
      METHODS: MEDLINE, Web of Science, CINAHL, Scopus, and EMBASE were searched for
      eligible studies. Quality assessment was undertaken using GRADE (Grading of
      Recommendations Assessment, Development and Evaluation) criteria. Raw data from
      studies meeting inclusion criteria was pooled for meta-analysis of effect
      estimates. Sensitivity analysis was performed for all outcomes. Funnel plot was
      performed to assess for publication bias. RESULTS: Thirteen studies met the
      inclusion criteria, and reported results in 1,378 patients with IBD. All included
      studies had a high risk of bias in at least one quality domain. The pooled risk
      ratio (RR) of loss of clinical response to IFX in patients with IBD who had ATIs
      was 3.2 (95% confidence interval (CI): 2.0-4.9, P<0.0001), when compared with
      patients without ATIs. This effect estimate was predominantly based on data from
      patients (N=494) with Crohn's disease (RR: 3.2, 95% CI: 1.9-5.5, P<0.0001). Data
      only from patients with ulcerative colitis (n=86) exhibited a non-significant RR
      of loss of response of 2.2 (95% CI: 0.5-9.0, P=0.3) in those with ATIs.
      Heterogeneity existed between studies, in both methods of ATI detection, and
      clinical outcomes reported. Three studies (n=243) reported trough serum IFX
      levels according to ATI status; the standardized mean difference in trough serum
      IFX levels between groups was -0.8 (95% CI -1.2, -0.4, P<0.0001). A funnel plot
      suggested the presence of publication bias. CONCLUSIONS: The presence of ATIs is
      associated with a significantly higher risk of loss of clinical response to IFX
      and lower serum IFX levels in patients with IBD. Published studies on this topic
      lack uniform reporting of outcomes. High risk of bias was present in all the
      included studies.

PMID- 23147528
TI  - Identification of interstitial Cajal-like cells in the human thoracic duct.
AB  - Interstitial Cajal-like cells (ICLCs) are speculated to be pacemakers in smooth
      muscle tissues. While the human thoracic duct (TD) is spontaneously active, the
      origin of this activity is unknown. We hypothesized that ICLCs could be present
      in the TD and using histological techniques, immunohistochemistry and
      immunofluorescence we have investigated the presence of ICLCs, protein markers
      for ICLCs and the cellular morphology of the human TD. Transmission electron
      microscopy was employed to investigate ultrastructure. Methylene blue staining,
      calcium-dependent fluorophores and confocal microscopy were used to identify
      ICLCs in live tissue. Methylene blue stained cells with morphology suggestive of
      ICLCs in the TD. Immunoreactivity localized the ICLC protein markers c-kit, CD34
      and vimentin to many cells and processes associated with smooth muscle cells
      (SMCs): coexpression of c-kit with vimentin or CD34 was observed in some cells.
      Electron microscopy analysis confirmed ICLCs as a major cell type of the human
      TD. Lymphatic ICLCs possess caveolae, dense bands, a patchy basal lamina,
      intermediate filaments and specific junctions to SMCs. ICLCs were
      ultrastructurally differentiable from other interstitial cells observed:
      fibroblasts, mast cells, macrophages and pericytes. Lymphatic ICLCs were
      localized to the subendothelial region of the wall as well as in intimate
      association with smooth muscle bundles throughout the media. ICLCs were
      morphologically distinct with multiple processes and also spindle shapes.
      Confocal imaging with calcium-dependent fluorophores corroborated cell morphology
      and localization observed in fixed tissues. Lymphatic ICLCs thus constitute a
      significant cell type of the human TD and physically interact with lymphatic
      SMCs.

PMID- 23147529
TI  - Ecological risk assessment of atrazine in North American surface waters.

PMID- 23147530
TI  - Arsenic speciation of geothermal waters in New Zealand.
AB  - Total arsenic and four arsenic species; arsenite (iAs(III)), arsenate (iAs(V)),
      dimethylarsinic acid (DMA(V)) and monomethylarsonic acid (MA(V)), are reported in
      28 geothermal features from the Taupo Volcanic Zone (TVZ) and Waikato region of
      New Zealand. Samples were collected for arsenic speciation analysis via a solid
      phase extraction (SPE) kit allowing the separation, stabilisation and pre
      concentration of the species at the time of sample collection in the field. This
      is the first research to present data for arsenic species collected by this
      technique in geothermal waters from New Zealand. Total arsenic concentrations,
      determined by inductively coupled plasma mass spectrometry (ICP-MS), ranged from
      0.008 to 9.08 mg l-1 As. The highest levels were discovered in three features in
      Tokaanu (Taumatapuhipuhi, Takarea #5 and #6), with arsenic concentrations of
      8.59, 8.70 and 9.08 mg l-1 As, respectively. Inorganic arsenic species were
      predominant in the geothermal waters, with arsenite contributing to more than 70%
      of the total arsenic in the majority of samples. Organic species were also
      determined in all samples, indicating the presence of microbial activity. A
      potential risk to human health was highlighted due to the high levels of arsenic,
      mainly as arsenite, in geothermal features linked to bathing pools. Further
      research is needed into dermal absorption as a potential route of arsenic
      exposure whilst bathing in these hot pools, as it may contribute to an occurrence
      of acute arsenic-related health problems.

PMID- 23147531
TI  - Bacterial biofilm composition in caries and caries-free subjects.
AB  - BACKGROUND: Certain major pathogens such as Streptococcus mutans, Lactobacillus
      spp. and others have been reported to be involved in caries initiation and
      progression. Yet, in addition to those leading pathogens, microbial communities
      seem to be much more diverse and individually differing. The aim of this study,
      therefore, was to analyze the bacterial composition of carious dentin and the
      plaque of caries-free patients by using a custom-made, real-time quantitative
      polymerase chain reaction assay (RQ-PCR). METHODS: The study included 26 patients
      with caries and 28 caries-free controls. Decayed tooth substance and plaque
      samples were harvested. Bacterial DNA was extracted and tested for the presence
      of 43 bacterial species or species groups using RQ-PCR. RESULTS: Relative
      quantification revealed that Propionibacterium acidifaciens was significantly
      more abundant in caries samples than were other microorganisms (fold change
      169.12, p = 0.023). In the caries-free samples, typical health-associated species
      were significantly more prevalent. Unsupervised hierarchical cluster analysis
      showed a high abundance of P. acidifaciens in caries subjects and distinct but
      individually differing bacterial clusters in the caries-free subjects. The
      distribution of 11 bacteria allowed full discrimination between caries and caries
      free subjects. CONCLUSION: Within the investigated cohort, P. acidifaciens was
      the only pathogen significantly more abundant in caries subjects. Cluster
      analysis yielded a diverse flora in caries-free subjects, whereas it was narrowed
      down to a small range of a few outcompeting members in caries subjects.

PMID- 23147532
TI  - Assessment of management of cardiovascular risk factors in patients with thoracic
      aortic disease.
AB  - BACKGROUND: Cardiovascular risk profiles and adiposity assessment data in
      patients with thoracic aortic disease (TAD) are sparse. HYPOTHESIS: Despite the
      fact that TAD patients are considered as a high-risk population, they will not be
      managed as aggressively as they should in terms of their cardiovascular risk
      profile. MATERIALS AND METHODS: Anthropometric, blood pressure (BP) data, and
      blood samples were collected prospectively from patients followed at our TAD
      dedicated clinic. The same measures have been taken in a control group initiating
      a cardiac rehabilitation program. RESULTS: In all, 286 patients with TAD and 116
      controls were recruited. BMI was higher among the controls than the patients with
      TAD (30.0+/-6.1 vs. 27.2+/-4.9 kg/m(2), respectively; P<0.001). We found no
      statistical difference between the groups for waist circumference (TAD: 93.1+/
      15.2 and 103.6+/-14.5 cm, control: 95.0+/-13.4 and 106.3+/-14.8 cm, respectively,
      for women and men; P=0.06). In terms of lipid profile, low-density lipoprotein
      cholesterol was 2.44+/-0.88 in patients with TAD and 2.09+/-0.82 mmol/l in the
      controls (P<0.001). A higher percentage of patients with TAD had low-density
      lipoprotein cholesterol values that were beyond the target (63.3% in TAD vs.
      46.1% in control; P<0.01). The values of apolipoprotein-B were similar between
      groups (P=0.41). BP was higher in patients with TAD (135+/-19/76+/-11 mmHg)
      versus the controls (129+/-17/71+/-11 mmHg; P<0.01). On the basis of ambulatory
      BP monitoring, 49.3% of patients with TAD were not well controlled for daytime
      and/or night-time BP. CONCLUSION: Cardiovascular risk factors, particularly BP,
      are not well controlled in patients with TAD followed in a dedicated clinic when
      compared with another high-risk control group in a cardiac rehabilitation
      program.

PMID- 23147533
TI  - Twenty-four-hour ambulatory blood pressure monitoring in the follow-up of the
      univentricular heart after Fontan repair.
AB  - BACKGROUND: In a univentricular heart corrected with a Fontan repair (UVH-F), a
      single pumping chamber is responsible for both systemic and pulmonary
      circulations. To evaluate the influence of afterload on cardiac output (CO) of
      UVH-F, this study aimed at (a) evaluating 24-h ambulatory blood pressure
      monitoring (ABPM) data of a group of UVH-F patients compared with a control group
      of healthy individuals (C) and (b) examining possible correlations between
      afterload measure [elastance (Ea)] derived from ABPM with (i) CO as calculated
      from pulse pressure and heart rate (ii) cardiac index (CI) as calculated from
      pulse pressure, heart rate and body surface. METHODS: Ten UHV-F patients (four
      males, six females, mean age at study: 12.6+/-0.6 years, and mean time from
      surgery: 7.2+/-1.7 years) were enrolled. A 24-h ABPM was performed. RESULTS: (UVH
      F vs. C) Systolic blood pressure (101+/-3 vs. 112+/-3 mmHg, P<0.0001); diastolic
      blood pressure (59+/-3 vs. 72+/-3 mmHg, P<0.0001); mean arterial ressure (73+/-3
      vs. 85+/-3 mmHg, P<0.0001); heart rate (68+/-6 vs. 87+/-5 beats/min, P<0.0001);
      CO (2.85+/-0.4 vs. 3.48+/-0.2 l/min, P<0.0001); and CI (2.51+/-0.2 vs. 2.92+/-0.1
      l/min/m(2), P<0.0001) were determined. In UVH-F, CO was related inversely to E(a)
      (r=-0.81, P<0.004). CI and E(a) were also related (r=+/-0.82, P<0.003). CO and
      time since surgery were inversely related (r=-0.98, P<0.0001). CONCLUSION: In UVH
      F 24 h, single ventricle afterload and CO are inversely related. When correcting
      CO for body surface to obtain CI, the graphic representation of their reciprocal
      relationship appears to be more explanatory for UVH-F haemodynamics.

PMID- 23147534
TI  - Validation of the Beurer BM 44 upper arm blood pressure monitor for home
      measurement, according to the European Society of Hypertension International
      Protocol 2002.
AB  - OBJECTIVE: The present study aimed to validate the automated upper arm blood
      pressure (BP) measuring device BM 44 for home BP monitoring according to the 2002
      Protocol of the European Society of Hypertension. The most important new feature
      of the new device was an integrated 'WHO indicator', which categorizes the
      patient's individual result within the WHO recommendations for target BP by a
      coloured scale. METHODS: Systolic and diastolic BPs were measured sequentially in
      35 adult participants (16 men, 19 women) using a standard mercury y-tubed
      reference sphygmomanometer (two observers) and the BM 44 device (one supervisor).
      Ninety-nine pairs of comparisons were obtained from 15 participants in phase 1
      and a further 18 participants in phase 2 of the validation study. RESULTS: The BM
      44 device passed phase 1 of the validation study successfully with a number of
      absolute differences between device and observers of 5, 10 and 15 mmHg for at
      least 28 out of 25, 35 out of 35 and 40 out of 40 measurements, respectively. The
      device also achieved the targets for phases 2.1 and 2.2, with 23 and 26
      participants having had at least two of three device-observers differences within
      5 mmHg for systolic and diastolic BP, respectively. CONCLUSION: The Beurer BM 44
      upper arm BP monitor has passed the International Protocol requirements, and
      hence can be recommended for home use in adults.

PMID- 23147535
TI  - Validation of the iHealth BP3 upper-arm blood pressure monitor, for clinic use
      and self-measurement, according to the European Society of Hypertension
      International Protocol revision 2010.
AB  - OBJECTIVE: This study aimed to evaluate the performance of the iHealth BP3 upper
      arm blood pressure monitor, which is designed for clinic use and self-measurement
      of blood pressure using Apple touch devices as an interface. METHODS: The
      European Society of Hypertension International Protocol (ESH-IP) revision 2010
      for the validation of blood pressure measuring devices in adults was followed
      precisely. Ninty-nine couples of test device and reference blood pressure
      measurements were obtained during the study (three pairs for each of the 33
      participants). RESULTS: The 33 participants, age 47.1+/-12.3 years (age range 27
      69 years) and arm circumference 30.0+/-4.4 cm, had a mean systolic blood pressure
      (SBP) of 143.9+/-27.4 mmHg and a mean diastolic blood pressure (DBP) of 90.1+/
      18.3 mmHg. The device passed all of the requirements fulfilling the standards of
      the protocol, and the mean+/-SD device-observer difference was 2.8+/-4.2 mmHg for
      SBP and -0.4+/-3.5 mmHg for DBP. CONCLUSION: According to the results of the
      validation study on the basis of the ESH-IP revision 2010, the iHealth BP3 can be
      recommended for clinic use and self-measurement in an adult population.

PMID- 23147536
TI  - Are kiosk blood pressure readings trustworthy?

PMID- 23147537
TI  - Comparison between Mobil-O-Graph and the SphygmoCor device for central systolic
      blood pressure estimation:  consensus is required for 'validation protocols'.

PMID- 23147539
TI  - Molecular characterization of desmoid tumors: decryption of the enigma.

PMID- 23147540
TI  - Microscopic margins of resection influence primary gastrointestinal stromal tumor
      survival.
AB  - BACKGROUND: Primary gastrointestinal stromal tumors (GISTs) are stromal tumors
      that arise from the gastrointestinal tract. Both surgical resection and molecular
      therapy are crucial in the treatment of these tumors. This study analyzes the
      outcomes of 151 patients with GIST treated at 3 institutions. These institutions
      comprise the GISTologist Study Group and provided follow-up data. PATIENTS AND
      METHODS: 151 patients with primary GIST were admitted and treated at the St.
      Orsola-Malpighi University Hospital in Bologna, Italy, the Catholic University
      Hospital in Rome, Italy, and the Modena University Hospital and National Cancer
      Institute in Naples, Italy, over the past 11 years. Patient data as well as tumor
      and therapy variables were studied to identify factors predicting survival with a
      focus on the microscopic margins of resection. RESULTS: All 151 patients had
      primary disease without metastasis and underwent complete resection of gross
      disease. The 5-year disease-free survival rate was 77%. Disease-free survival was
      predicted by tumor size, mitotic count, and margins of resection. Recurrence of
      disease after resection was predominantly intra-abdominal. CONCLUSIONS: Tumor
      size, mitotic count, and microscopic margins of resection predict disease-free
      survival in patients with primary GIST.

PMID- 23147541
TI  - Overexpression of MMP-1 and VEGF-C is associated with a less favorable prognosis
      in esophageal squamous cell carcinoma.
AB  - BACKGROUND: This study addresses the association of matrix metalloproteinase-1
      (MMP-1) and vascular endothelial growth factor-C (VEGF-C) expression in
      esophageal squamous cell carcinoma (SCC) with clinicopathologic characteristics
      in the patients. MATERIAL AND METHODS: We profiled the expression of MMP-1 and
      VEGF-C by cDNA microarray in 4 cases and by reverse transcription-polymerase
      chain reaction (RT-PCR) in 14 cases of esophageal SCC. Another 90 cases were
      reviewed by immunohistochemical examination of paraffin-embedded sections.
      RESULTS: Expression of MMP-1 and VEGF-C mRNA in normal esophageal tissue and
      tumor tissue was compared. Data were fully consistent with the results of RT-PCR.
      Immunohistochemistry showed that compared to the normal mucosa MMP-1 and VEGF-C
      protein expression was upregulated in both esophageal atypical hyperplasia (n =
      16) and esophageal SCC. Depth of tumor invasion, lymph node metastasis, and
      clinical stage were directly associated with prognosis in all cases. Furthermore,
      median overall survival and disease-free survival were significantly shorter in
      patients with a higher expression of MMP-1 and VEGF-C than in patients with lower
      expression levels. CONCLUSION: We demonstrated that the expression of both MMP-1
      and VEGF-C mRNA and protein was upregulated in esophageal SCC tissues. Protein
      expression was associated with progressive tumor stage and poor prognosis in
      patients with esophageal SCC.

PMID- 23147542
TI  - Incidence and risk factors of bisphosphonate-related osteonecrosis of the jaw in
      multiple myeloma patients having undergone autologous stem cell transplantation.
AB  - BACKGROUND: Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is a severe
      complication of bisphosphonate therapy. Due to their long survival and
      subsequently high cumulative doses of bisphosphonates, multiple myeloma patients
      have the highest risk of developing BRONJ of all patients treated with
      bisphosphonates. The purpose of the present study was to evaluate the incidence
      and risk factors for BRONJ in multiple myeloma patients after high-dose
      chemotherapy and autologous stem cell transplantation (ASCT). PATIENTS AND
      METHODS: We retrospectively analyzed the data of 120 multiple myeloma patients
      after high-dose chemotherapy and ASCT treated with bisphosphonates and assessed
      the incidence and risk factors of BRONJ. RESULTS: Of the 120 patients, 23 (19%)
      developed BRONJ. 6 patients suffered several BRONJ events, resulting in a total
      incidence of 23%. The risk for BRONJ was significantly higher for patients with
      rheumatism and recent dental manipulations. Furthermore, the number of previous
      bisphosphonate rotations, the duration of bisphosphonate therapy, and the type
      and cumulative dose of bisphosphonate used were associated with the incidence of
      BRONJ. CONCLUSION: Our study is the first to determine the risk of BRONJ in a
      homogeneous group of multiple myeloma patients treated with high-dose
      chemotherapy and ASCT.

PMID- 23147543
TI  - The MDM2 309 T/G polymorphism is associated with head and neck cancer risk
      especially in nasopharyngeal cancer: a meta-analysis.
AB  - BACKGROUND: Published data on the association between mouse double minute 2
      (MDM2) 309 T/G single nucleotide polymorphism (SNP) and head and neck cancer
      (HNC) risk are inconclusive. To derive a more precise estimation of the
      relationship, we performed a meta-analysis. MATERIAL AND METHODS: A systematic
      computerized search of PubMed was performed. Crude odds ratios (ORs) with 95%
      confidence intervals (CIs) were used to assess the strength of association
      between the polymorphism and HNC risk. The pooled ORs were performed for TT
      versus GG, TG versus GG, dominant model (TT+TG vs. GG) and recessive model (TT
      vs. TG+GG), respectively. RESULTS: A total of 9 studies including 2,755 cases and
      4,121 controls were involved in the final meta-analysis. The results of the
      overall meta-analysis provided some evidence of an association between the
      polymorphism and HNC risk (OR = 0.82, 95% CI 0.67-0.99 for TG vs. GG). In the
      subgroup meta-analysis based on the types of tumor, we detected a significantly
      decreased NPC risk for all genetic models. CONCLUSION: This meta-analysis
      suggests that the GG genotype of MDM2 SNP309 is associated with HNC risk. The
      MDM2 SNP309G allele is a highly penetrant risk factor for developing NPC.

PMID- 23147544
TI  - RASSF1A and ERCC1 expression levels might be predictive of prognosis in advanced,
      recurrent, and metastatic squamous cell carcinoma of the head and neck treated
      with docetaxel and cisplatin.
AB  - BACKGROUND: The purpose of this study was to test the hypothesis that the
      immunohistochemical expression of ERCC1 and RASSF1A would predict both response
      to and survival after docetaxel and cisplatin combination chemotherapy in
      inoperable or recurrent head and neck squamous cell carcinoma. PATIENTS AND
      METHODS: A total of 54 patients were treated with frontline systemic chemotherapy
      composed of docetaxel (60 mg/m(2)) and cisplatin (65 mg/m(2)), every 3 weeks for
      up to 6 cycles. The expression levels of ERCC1 and RASSF1A were evaluated in the
      available 36 prechemotherapy samples. RESULTS: The overall objective response
      rate was 35% (complete remission 12% and partial remission 23%). The median
      progression-free survival and overall survival (OS) times were 5.0 months (95%
      confidence interval (CI), 3.7-6.4 months) and 24.2 months (95% CI, 3.5-45.0
      months), respectively. The status of low ERCC1 and high RASSF1A expression was an
      independent favorable prognostic factor for OS in multivariate analysis (p =
      0.043; hazard ratio, 7.224; 95% CI, 1.060-49.217). Toxicities were comparable
      with those of previously reported trials. CONCLUSIONS: Less intensive doses of
      cisplatin and docetaxel are active but not effective in reducing toxicity. Also,
      both ERCC1 and RASSF1A might be useful prognostic markers in this regimen.

PMID- 23147545
TI  - Molecular analysis of desmoid tumors with a high-density single-nucleotide
      polymorphism array identifies new molecular candidate lesions.
AB  - BACKGROUND: Desmoid tumors are neoplastic proliferations of connective tissues.
      The mutation status of the gene coding for catenin (cadherin-associated protein)
      beta 1 (CTNNB1) and trisomy 8 on the chromosomal level have been described to
      have prognostic relevance. PATIENTS AND METHODS: In order to elucidate new
      molecular mechanisms underlying these tumors, we carried out a molecular analysis
      with a genome-wide human high-density single-nucleotide polymorphism (SNP) array,
      in 9 patients. RESULTS: Single samples showed numerical aberrations on
      chromosomes (Chrs) 20 and 6 with either trisomy 20 or monosomy 6. No trisomy 8
      could be detected. Recurrent heterozygous deletions were found in Chr 5q
      (including the APC gene locus, n = 3) and Chr 8p23 (n = 4, containing coding
      regions for the potential tumor suppressor gene CSMD1). This novel deletion in
      8p23 showed an association with local recurrence. In addition, structural
      chromosomal changes (gain of Chrs 8 and 20) were found in a minority of cases.
      CONCLUSION: The genomic alteration affecting the candidate gene CSMD1 could be
      important in the development of desmoid tumors.

PMID- 23147547
TI  - Primary intracerebral myeloid sarcoma.
AB  - BACKGROUND: Myeloid sarcoma rarely presents in the absence of systemic myeloid
      disease. CASE REPORT: In this study, we present a case of intracerebral myeloid
      sarcoma with no diagnosis of any hematological disease in a 22-year-old male
      patient in whom brain magnetic resonance image revealed a meningioma. However,
      biopsy showed myeloid sarcoma. No myeloid disease was determined. The mass
      disappeared following 8 cycles of chemotherapy. In the literature, we determined
      only 8 similar cases cited between 1970 and 2011. CONCLUSION: Intracerebral
      myeloid sarcoma has currently no standard treatment and may be confused with a
      primary brain disease. Chemotherapy and/or radiotherapy are the most viable and
      widely used treatment modalities. Potential occurrence of hematological disease
      should also be closely followed due to conversion risks.

PMID- 23147546
TI  - Chronic myeloid leukemia as a secondary malignancy after lymphoma in a child. A
      case report and review of the literature.
AB  - BACKGROUND: Philadelphia chromosome-positive chronic myeloid leukemia (CML) in
      children is very rare. CML occurring as a secondary malignancy in individuals
      treated for diffuse large B-cell lymphoma (DLBCL) is also rare. CASE REPORT: We
      present the case of a 5-year-old female patient who developed a right orbital
      mass that was diagnosed as DLBCL. 9 months after receiving treatment for DLBCL,
      she presented with a white cell count of 250,000/mm(3). Peripheral blood and bone
      marrow (BM) evaluation revealed a myeloproliferative disorder. Cytogenetic and
      molecular studies demonstrated the presence of t(9;22). CML following DLBCL has
      not been previously described in the younger population. To our knowledge, this
      is the first report of a child who developed a CML as a second malignancy after
      DLBCL. Therapy-related CML and non-therapy-related secondary CML are discussed as
      potential explanations of this highly unusual clinical presentation. CONCLUSION:
      Hematological disorders such as CML may occur after lymphomas. With the increased
      use of BM cytogenetic studies during staging for lymphoid malignancies, future
      studies may be able to clarify the question of whether the CML clone in some of
      these patients existed before treatment for lymphoma.

PMID- 23147548
TI  - Limbic Encephalitis due to Pancreatic Cancer.

PMID- 23147549
TI  - Expression of costimulatory molecule B7-H4 in human malignant tumors.
AB  - Costimulatory molecule B7-H4, a member of the B7 family, negatively regulates the
      immune response of T cells through inhibiting their proliferation, cytokine
      production and cell cycle. The overexpression of B7-H4 plays an important role in
      initiation, progression and regression of tumors by promoting malignant
      transformation of epithelial cells and protecting epithelial cells from anoikis.
      B7-H4 expression in malignant tumors is useful for clinical diagnosis, and may
      provide a novel molecular target for cancer treatment.

PMID- 23147550
TI  - SOD1 in cerebral spinal fluid as a pharmacodynamic marker for antisense
      oligonucleotide therapy.
AB  - BACKGROUND: Therapies designed to decrease the level of SOD1 are currently in a
      clinical trial for patients with superoxide dismutase (SOD1)-linked familial
      amyotrophic lateral sclerosis (ALS). OBJECTIVE: To determine whether the SOD1
      protein in cerebral spinal fluid (CSF) may be a pharmacodynamic marker for
      antisense oligonucleotide therapy and a disease marker for ALS. DESIGN: Antisense
      oligonucleotides targeting human SOD1 were administered to rats expressing
      SOD1G93A. The human SOD1 protein levels were measured in the rats' brain and CSF
      samples. In human CSF samples, the following proteins were measured: SOD1, tau,
      phosphorylated tau, VILIP-1, and YKL-40. PARTICIPANTS: Ninety-three participants
      with ALS, 88 healthy controls, and 89 controls with a neurological disease (55
      with dementia of the Alzheimer type, 19 with multiple sclerosis, and 15 with
      peripheral neuropathy). RESULTS: Antisense oligonucleotide-treated SOD1G93A rats
      had decreased human SOD1 messenger RNA levels (mean [SD] decrease of 69% [4%])
      and decreased protein levels (mean [SD] decrease of 48% [14%]) in the brain. The
      rats' CSF samples showed a similar decrease in hSOD1 levels (mean [SD] decrease
      of 42% [14%]). In human CSF samples, the SOD1 levels varied a mean (SD) 7.1%
      (5.7%) after additional measurements, separated by months, were performed. The
      CSF SOD1 levels were higher in the participants with ALS (mean [SE] level, 172
      [8] ng/mL; P<.05) and the controls with a neurological disease (mean [SE] level,
      172 [6] ng/mL; P<.05) than in the healthy controls (mean [SE] level, 134 [4]
      ng/mL). Elevated CSF SOD1 levels did not correlate with disease characteristics
      in participants with ALS or controls with dementia of the Alzheimer type, but
      they did correlate with tau, phosphorylated tau, VILIP-1 and YKL-40 levels in
      controls with dementia of the Alzheimer type. CONCLUSIONS: SOD1 in CSF may be an
      excellent pharmacodynamic marker for SOD1-lowering therapies because antisense
      oligonucleotide therapy lowers protein levels in the rat brain and rat CSF
      samples and because SOD1 levels in CSF samples from humans are stable over time.

PMID- 23147551
TI  - Developmental origins of astrocyte heterogeneity: the final frontier of CNS
      development.
AB  - Astrocytes are the most abundant cell type in the central nervous system, have
      diverse physiological roles in both health and disease, and exhibit phenotypic
      heterogeneity. In spite of the overwhelming evidence that astrocytes are a
      diverse population, there has been relatively little consideration of their
      molecular heterogeneity. In this review, we will summarize what is known about
      the heterogeneity of astrocytes and outline challenges that have limited studies
      understanding their molecular diversity. Approaches that have sought to overcome
      these limitations will be discussed, with an emphasis on recent progress in the
      field of developmental gliogenesis, which has revealed that positional identity
      during embryogenesis is an organizing feature of astrocyte diversity. These
      recent findings, coupled with emerging technologies that allow for direct
      isolation of astrocyte populations, have led us to propose that approaches rooted
      in astrocyte development may be the key to unlocking this immense, untapped
      diversity.

PMID- 23147553
TI  - Return to work after coronary angioplasty or heart surgery: a 5-year experience
      with the "CardioWork" protocol.
AB  - OBJECTIVE: The "CardioWork" protocol, for work resumption after invasive heart
      procedures and subsequent cardiac rehabilitation, is presented. METHODS: Over 5
      years, 107 consecutive patients of working age were enrolled. Jobs were
      classified as multiples of basal metabolism according to the entity of physical
      strain. These data were integrated with instrumental evaluations to provide
      indications regarding time and modality of work resumption. RESULTS: A total of
      89.7% of patients resumed working. Other relevant findings include the
      correlation of time for work resumption with the kind of treatment and the task
      energy requirement; the earliness of return to work, even for older people and
      those performing heavy tasks; and the difficulty of work resumption for those who
      failed to restart work within 6 months. CONCLUSIONS: This study highlights the
      importance of a multidisciplinary rehabilitative approach to facilitate work
      resumption, adapting the work tasks to the changed psychophysical capabilities.

PMID- 23147552
TI  - Portable upper extremity robotics is as efficacious as upper extremity
      rehabilitative therapy: a randomized controlled pilot trial.
AB  - OBJECTIVE: To compare the efficacy of a repetitive task-specific practice regimen
      integrating a portable, electromyography-controlled brace called the 'Myomo'
      versus usual care repetitive task-specific practice in subjects with chronic,
      moderate upper extremity impairment. SUBJECTS: Sixteen subjects (7 males; mean
      age 57.0 +/- 11.02 years; mean time post stroke 75.0 +/- 87.63 months; 5 left
      sided strokes) exhibiting chronic, stable, moderate upper extremity impairment.
      INTERVENTIONS: Subjects were administered repetitive task-specific practice in
      which they participated in valued, functional tasks using their paretic upper
      extremities. Both groups were supervised by a therapist and were administered
      therapy targeting their paretic upper extremities that was 30 minutes in
      duration, occurring 3 days/week for eight weeks. One group participated in
      repetitive task-specific practice entirely while wearing the portable robotic,
      while the other performed the same activity regimen manually. MAIN OUTCOME
      MEASURES: The upper extremity Fugl-Meyer, Canadian Occupational Performance
      Measure and Stroke Impact Scale were administered on two occasions before
      intervention and once after intervention. RESULTS: After intervention, groups
      exhibited nearly identical Fugl-Meyer score increases of ~2.1 points; the group
      using robotics exhibited larger score changes on all but one of the Canadian
      Occupational Performance Measure and Stroke Impact Scale subscales, including a
      12.5-point increase on the Stroke Impact Scale recovery subscale. CONCLUSIONS:
      Findings suggest that therapist-supervised repetitive task-specific practice
      integrating robotics is as efficacious as manual practice in subjects with
      moderate upper extremity impairment.

PMID- 23147554
TI  - Process evaluation of a workplace health promotion intervention aimed at
      improving work engagement and energy balance.
AB  - OBJECTIVE: To evaluate the process of the implementation of an intervention aimed
      at improving work engagement and energy balance, and to explore associations
      between process measures and compliance. METHODS: Process measures were assessed
      using a combination of quantitative and qualitative methods. RESULTS: The
      mindfulness training was attended at least once by 81.3% of subjects, and 54.5%
      were highly compliant. With regard to e-coaching and homework exercises, 6.3% and
      8.0%, respectively, were highly compliant. The training was appreciated with a
      7.5 score and e-coaching with a 6.8 score. Appreciation of training and e
      coaching, satisfaction with trainer and coach, and practical facilitation were
      significantly associated with compliance. CONCLUSION: The intervention was
      implemented well on the level of the mindfulness training, but poorly on the
      level of e-coaching and homework time investment. To increase compliance,
      attention should be paid to satisfaction and trainer-participant relationship.

PMID- 23147555
TI  - Risk of selected cancers due to occupational exposure to chlorinated solvents in
      a case-control study in Montreal.
AB  - OBJECTIVE: To evaluate the association between exposure to chlorinated solvents
      and cancer. METHODS: We conducted a case-control study of occupational exposures
      and cancer in Montreal, Quebec, Canada, including 3730 cancer cases and 533
      population controls. Occupational exposures were derived using a combination of
      subject-reported job history and expert assessment. We examined the associations
      between two chemical families and six chlorinated solvents with 11 sites of
      cancer. RESULTS: The majority of the associations examined were null, although
      many were based on small numbers. We found two significantly elevated odds ratios
      (ORs), one between perchloroethylene and prostate cancer (OR = 4.3; 95% CI: 1.4
      to 13) and another between trichloroethylene and melanoma (OR = 3.2; 95% CI: 1.0
      to 9.9). CONCLUSIONS: There was little evidence of associations between
      chlorinated solvents and cancer. Limited power precludes strong inferences about
      absence of risk. We raise hypotheses about two possible associations:
      perchloroethylene with prostate cancer and trichloroethylene with melanoma.

PMID- 23147556
TI  - Computational studies on the adsorption of CO2 in the flexible perfluorinated
      metal-organic framework zinc 1,2-bis(4-pyridyl)ethane tetrafluoroterephthalate.
AB  - Carbon dioxide adsorption sites within the flexible metal-organic framework (MOF)
      zinc 1,2-bis(4-pyridyl)ethane tetrafluoroterephthalate (Znbpetpa) were
      investigated using density functional theory (DFT) and canonical Monte Carlo (MC)
      calculations. Two types of sites with different heats of adsorption were found by
      using DFT and confirmed by the MC results. Expansion of the cavities occurred
      simultaneously with gas uptake and the process of "breathing" within the MOF was
      identified. The presence of such a mechanism makes the understanding of this
      structure useful in tuning the design of MOFs for permanent trapping of gases.

PMID- 23147557
TI  - PPAR-gamma2 and PTPRD gene polymorphisms influence type 2 diabetes patients'
      response to pioglitazone in China.
AB  - AIM: To investigate the influence of peroxisome proliferator-activated receptor
      gamma2 (PPAR-gamma2) gene polymorphism rs1801282 and protein tyrosine phosphatase
      receptor type D (PTPRD) gene polymorphism rs17584499 on the occurrence of type 2
      diabetes and pioglitazone efficacy in a Chinese Han population. METHODS: One
      hundred ninety seven type 2 diabetes patients and 212 healthy controls were
      enrolled. Among them, 67 type 2 diabetes patients were administered pioglitazone
      (30 mg/d, po) for 3 months. All the subjects were genotyped for genetic variants
      in PPAR-gamma2 and PTPRD using MALDI-TOF mass spectrometry. Fasting plasma
      glucose, postprandial plasma glucose, glycated hemoglobin, serum triglyceride,
      total cholesterol, low-density and high-density lipoprotein-cholesterol were
      determined. RESULTS: The PPAR-gamma2 gene rs1801282 polymorphism was
      significantly associated with type 2 diabetes susceptibility (OR=0.515, 95% CI
      0.268-0.990) and the PTPRD gene rs17584499 polymorphism was also significantly
      associated with type 2 diabetes (OR=1.984, 95% CI 1.135-3.469) in a dominant
      model adjusted for age, gender and BMI. After pioglitazone treatment for 3
      months, the type 2 diabetes patients with PPAR-gamma2 rs1801282 CG genotypes
      significantly showed higher differential values of postprandial plasma glucose
      and serum triglyceride compared with those with rs1801282 CC genotype. The
      patients with PTPRD rs17584499 CT+TT genotypes showed significantly lower
      differential value of postprandial plasma glucose compared to those with
      rs17584499 CC genotype. CONCLUSION: Diabetes risk alleles in PPAR-gamma2
      (rs1801282) and PTPRD (rs17584499) are associated with pioglitazone therapeutic
      efficacy.

PMID- 23147559
TI  - Functional ability, mobility, and pain before and after knee replacement in
      patients aged 75 and older: a cross-sectional study.
AB  - BACKGROUND AND AIMS: The purpose of the present cross-sectional study was to
      analyze how knee replacement affects performance in activities of daily living
      (ADL), mobility, and pain in older patients with knee osteoarthritis. METHODS:
      Knee osteoarthritis patients aged >=75 years scheduled for knee replacement
      (Group 0, n=68), or having undergone knee replacement one (Group 1, n=71) or two
      years (Group 2, n=75) earlier, were sent a questionnaire asking about ADL
      performance, mobility, degree of pain, use of analgesics, and patient's
      perception of the outcome. RESULTS: More patients having had knee replacement
      than those waiting for surgery reported they were able to perform ADLs without
      difficulty, the exception being bathing and dressing/undressing. They also had a
      better performance in mobility measures (ability to move indoors and use stairs,
      walking distance). After adjustment for age, gender, and anesthesiological risk
      score, the patients in Groups 1 and 2 continued to show better performance than
      the patients in Group 0 in rising from chair, heavy housework, moving indoors,
      using stairs, and walking 400 m. Ninety-three percent of patients in Group 0 but
      only 23% and 34% in Groups 1 and 2 used analgesics for knee pain. The majority of
      the patients in Groups 1 and 2 were satisfied with the outcome and estimated that
      their health and mobility had improved after surgery. CONCLUSIONS: Knee
      osteoarthritis patients aged >=75 years, having undergone knee replacement, have
      not only less pain and better mobility but also superior ADL performance than
      patients scheduled for surgery.

PMID- 23147558
TI  - Efficacy of subantimicrobial-dose doxycycline against nitrosative stress in
      chronic periodontitis.
AB  - AIM: To evaluate the effectiveness of subantimicrobial-dose doxycycline (SDD) as
      an adjunct to scaling and root planing (SRP) treatment against the nitrosative
      stress of moderate to advanced chronic periodontitis. METHODS: Adults with
      untreated chronic periodontitis (n=174) were randomly administered SRP+SDD (n=87)
      (20 mg of doxycycline twice daily) or SRP+placebo (n=87) treatment for 3 months.
      At baseline and after 3 months, the probing depths (PD), bleeding on probing
      (BOP) and clinical attachment level (CAL) were measured, and a gingivomucosal
      biopsy was collected to assay the induction of nitric oxide synthase (iNOS) and 3
      nitrotyrosine (3NT), and blood was collected to assay for total nitrites and
      nitrates (NO(x)) and 3NT. RESULTS: Compared to baseline, at the completion of
      treatment, significant decreases in the levels of tissue iNOS and 3NT and serum
      NO(x) and 3NT were observed in both groups. SRP+SDD yielded a greater reduction
      in the gingivomucosal and serum nitrosative stress markers than did SRP+placebo.
      PD, BOP, and CAL reduction were correlated with the nitrosative stress
      parameters. CONCLUSION: On a short-term basis, SDD therapy may be used as an
      adjunct to SRP treatment against nitrosative stress in moderate to advanced
      chronic periodontitis.

PMID- 23147560
TI  - Successful treatment of hepatic sinusoidal obstructive syndrome after
      hematopoietic stem cell transplantation in a child using recombinant
      thrombomodulin.

PMID- 23147561
TI  - Human CD4 T cell epitopes selective for Vaccinia versus Variola virus.
AB  - Due to the high degree of sequence identity between Orthopoxvirus species, the
      specific B and T cell responses raised against these viruses are largely cross
      reactive and poorly selective. We therefore searched for CD4 T cell epitopes
      present in the conserved parts of the Vaccinia genome (VACV) but absent from
      Variola viruses (VARV), with a view to identifying immunogenic sequences
      selective for VACV. We identified three long peptide fragments from the B7R, B10R
      and E7R proteins by in silico comparisons of the poxvirus genomes, and evaluated
      the recognition of these fragments by VACV-specific T cell lines derived from
      healthy donors. For the 12 CD4 T cell epitopes identified, we assessed their
      binding to common HLA-DR allotypes and their capacity to induce peptide-specific
      CD4 T-cell lines. Four peptides from B7R and B10R displayed a broad binding
      specificity for HLA-DR molecules and induced multiple T cell lines from healthy
      donors. Besides their absence from VARV, the two B10R peptide sequences were
      mutated in the Cowpox virus and completely absent from the Monkeypox genome. This
      work contributes to the development of differential diagnosis of poxvirus
      infections.

PMID- 23147562
TI  - NTPDase and 5'-nucleotidase activities from synaptosomes and platelets of rats
      exposed to cadmium and treated with N-acetylcysteine.
AB  - The purpose of the present investigation was to evaluate the hydrolysis of
      adenine nucleotides on synaptosomes and platelets obtained from rats exposed to
      cadmium (Cd) and treated with N-acetylcysteine (NAC). Rats received Cd (2 mg/kg)
      and NAC (150 mg/kg) by gavage every other day for 30 days. Animals were divided
      into four groups (n = 4-6): control/saline, NAC, Cd, and Cd/NAC. The results of
      this study demonstrated that NTPDase and 5'-nucleotidase activities were
      increased in the cerebral cortex synaptosomes of Cd-poisoned rats, and NAC co
      treatment reversed these activities to the control levels. In relation to
      hippocampus synaptosomes, no differences on the NTPDase and 5'-nucleotidase
      activities of Cd-poisoned rats were observed and only the 5'-nucleotidase
      activity was increased by the administration of NAC per se. In platelets, Cd
      intoxicated rats showed a decreased NTPDase activity and no difference in the 5'
      nucleotidase activity; NAC co-treatment was inefficient in counteracting this
      undesirable effect. Our findings reveal that adenine nucleotide hydrolysis in
      synaptosomes and platelets of rats were altered after Cd exposure leading to a
      compensatory response in the central nervous system and acting as a modulator of
      the platelet activity. NAC was able to modulate the purinergic system which is
      interesting since the regulation of these enzymes could have potential
      therapeutic importance. Thus, our results reinforce the importance of the study
      of the ecto-nucleotidases pathway in poisoning conditions and highlight the
      possibility of using antioxidants such as NAC as adjuvant against toxicological
      conditions.

PMID- 23147563
TI  - Salt-induced aggregation of a monoclonal human immunoglobulin G1.
AB  - Physical stability is critical for any therapeutic protein's efficacy and
      economic viability. No reliable theory exists to predict stability de novo, and
      modeling aggregation is challenging as this phenomenon can involve orientation
      effects, unfolding, and the rearrangement of noncovalent bonds inter- and
      intramolecularly in a complex sequence of poorly understood events. Despite this
      complexity, the simple observation of protein concentration-dependent diffusivity
      in stable, low ionic-strength solutions can provide valuable information about a
      protein's propensity to aggregate at higher salt concentrations and over longer
      times. We recently verified this notion using two model proteins, and others have
      shown that this strategy may be applicable to antibodies as well. Here, we expand
      our previous study to a monoclonal human immunoglobulin G1 antibody and discuss
      both merits and limitations of stability assessments based on the diffusional
      virial coefficient k(D). We find this parameter to be a good predictor of
      relative protein stability in solutions of different chaotropic salts, and a
      telling heuristic for the effect of kosmotropes. Both temperature and
      glycosylation are seen to have a strong influence on k(D), and we examine how
      these factors affect stability assessments. Protein unfolding is monitored with a
      fluorescence assay to assist in interpreting the observed aggregation rates.

PMID- 23147564
TI  - On topological indices for small RNA graphs.
AB  - The secondary structure of RNAs can be represented by graphs at various
      resolutions. While it was shown that RNA secondary structures can be represented
      by coarse grain tree-graphs and meaningful topological indices can be used to
      distinguish between various structures, small RNAs are needed to be represented
      by full graphs. No meaningful topological index has yet been suggested for the
      analysis of such type of RNA graphs. Recalling that the second eigenvalue of the
      Laplacian matrix can be used to track topological changes in the case of coarse
      grain tree-graphs, it is plausible to assume that a topological index such as the
      Wiener index that represents all Laplacian eigenvalues may provide a similar
      guide for full graphs. However, by its original definition, the Wiener index was
      defined for acyclic graphs. Nevertheless, similarly to cyclic chemical graphs,
      small RNA graphs can be analyzed using elementary cuts, which enables the
      calculation of topological indices for small RNAs in an intuitive way. We show
      how to calculate a structural descriptor that is suitable for cyclic graphs, the
      Szeged index, for small RNA graphs by elementary cuts. We discuss potential uses
      of such a procedure that considers all eigenvalues of the associated Laplacian
      matrices to quantify the topology of small RNA graphs.

PMID- 23147566
TI  - Optimal mapping of terrestrial gamma dose rates using geological parent material
      and aerogeophysical survey data.
AB  - Regulatory authorities need ways to estimate natural terrestrial gamma radiation
      dose rates (nGy h-1) across the landscape accurately, to assess its potential
      deleterious health effects. The primary method for estimating outdoor dose rate
      is to use an in situ detector supported 1 m above the ground, but such
      measurements are costly and cannot capture the landscape-scale variation in dose
      rates which are associated with changes in soil and parent material mineralogy.
      We investigate the potential for improving estimates of terrestrial gamma dose
      rates across Northern Ireland (13,542 km2) using measurements from 168 sites and
      two sources of ancillary data: (i) a map based on a simplified classification of
      soil parent material, and (ii) dose estimates from a national-scale, airborne
      radiometric survey. We used the linear mixed modelling framework in which the two
      ancillary variables were included in separate models as fixed effects, plus a
      correlation structure which captures the spatially correlated variance component.
      We used a cross-validation procedure to determine the magnitude of the prediction
      errors for the different models. We removed a random subset of 10 terrestrial
      measurements and formed the model from the remainder (n = 158), and then used the
      model to predict values at the other 10 sites. We repeated this procedure 50
      times. The measurements of terrestrial dose vary between 1 and 103 (nGy h-1). The
      median absolute model prediction errors (nGy h-1) for the three models declined
      in the following order: no ancillary data (10.8) > simple geological
      classification (8.3) > airborne radiometric dose (5.4) as a single fixed effect.
      Estimates of airborne radiometric gamma dose rate can significantly improve the
      spatial prediction of terrestrial dose rate.

PMID- 23147565
TI  - Identification of novel splice variants and exons of human endothelial cell
      specific chemotaxic regulator (ECSCR) by bioinformatics analysis.
AB  - Recent discovery of biological function of endothelial cell-specific chemotaxic
      regulator (ECSCR), previously known as endothelial cell-specific molecule 2
      (ECSM2), in modulating endothelial cell migration, apoptosis, and angiogenesis,
      has made it an attractive molecule in vascular research. Thus, identification of
      splice variants of ECSCR could provide new strategies for better understanding
      its roles in health and disease. In this study, we performed a series of blast
      searches on the human EST database with known ECSCR cDNA sequence (Variant 1),
      and identified additional three splice variants (Variants 2-4). When examining
      the ECSCR gene in the human genome assemblies, we found a large unknown region
      between Exons 9 and 11. By PCR amplification and sequencing, we partially mapped
      Exon 10 within this previously unknown region of the ECSCR gene. Taken together,
      in addition to previously reported human ECSCR, we identified three novel full
      length splice variants potentially encoding different protein isoforms. We
      further defined a total of twelve exons and nearly all exon-intron boundaries of
      the gene, of which only eight are annotated in current public databases. Our work
      provides new information on gene structure and alternative splicing of the human
      ECSCR, which may imply its functional complexity. This undoubtedly opens new
      opportunities for future investigation of the biological and pathological
      significance of these ECSCR splice variants.

PMID- 23147567
TI  - Uptake and toxicity of polycyclic aromatic hydrocarbons in terrestrial
      springtails--studying bioconcentration kinetics and linking toxicity to chemical
      activity.
AB  - Passive dosing applies a polymer loaded with test compound(s) to establish and
      maintain constant exposure in laboratory experiments. Passive dosing with the
      silicone poly(dimethylsiloxane) was used to control exposure of the terrestrial
      springtail Folsomia candida to six polycyclic aromatic hydrocarbons (PAHs) in
      bioconcentration and toxicity experiments. Folsomia candida could move freely on
      the PAH-loaded silicone, resulting in exposure via air and direct contact. The
      bioconcentration kinetics indicated efficient uptake of naphthalene, anthracene,
      and pyrene through air and (near) equilibrium partitioning of these PAHs to
      lipids and possibly the waxy layer of the springtail cuticle. Toxicities of
      naphthalene, phenanthrene, and pyrene were related to chemical activity, which
      quantifies the energetic level and drives spontaneous processes including
      diffusive biouptake. Chemical activity-response relationships yielded effective
      lethal chemical activities (La50s) well within the expected range for baseline
      toxicity (0.01-0.1). Effective lethal body burdens for naphthalene and pyrene
      exceeded the expected range of 2 to 8 mmol kg(-1) fresh weight, which again
      indicated the waxy layer to be a sorbing phase. Finally, chemical activities were
      converted into equilibrium partitioning concentrations in lipids yielding
      effective lethal concentrations for naphthalene and phenanthrene in good
      correspondence with the lethal membrane burden for baseline toxicity (40-160 mmol
      kg(-1) lipid). Passive dosing was a practical approach for tightly controlling
      PAH exposure, which in turn provided new experimental possibilities and findings.

PMID- 23147568
TI  - Gluten free diet adherence in coeliac disease. The role of psychological symptoms
      in bridging the intention-behaviour gap.
AB  - This study examined the potential role of psychological symptoms in limiting the
      translation of positive intention into strict gluten free diet (GFD) adherence in
      coeliac disease (CD) within a theory of planned behaviour (TPB) framework. It was
      hypothesised that participants with more symptomatic psychological profiles would
      exhibit poorer adherence, primarily in the context of positive intentions.
      Coeliac disease participants (N=390) completed online measures of gluten free
      diet adherence, psychological symptoms, coping behaviour, and TPB items.
      Intention and behaviour were moderately correlated, confirming the existence of
      the intention-behaviour gap. Psychological symptoms accounted for additional
      variance over and above TPB variables in GFD adherence but not intention.
      Participants who failed to act on their positive intentions displayed more
      psychological symptoms and greater reliance on maladaptive coping strategies than
      those with consistent intention-behaviour relationships (p<.01). The heightened
      incidence of psychological symptoms in CD has a small but significant negative
      impact on the ability to translate positive intentions into strict adherence.
      Directions for future research including interventions to improve GFD adherence
      are discussed.

PMID- 23147570
TI  - Predicting the oral uptake efficiency of chemicals in mammals: combining the
      hydrophilic and lipophilic range.
AB  - Environmental risk assessment requires models for estimating the bioaccumulation
      of untested compounds. So far, bioaccumulation models have focused on lipophilic
      compounds, and only a few have included hydrophilic compounds. Our aim was to
      extend an existing bioaccumulation model to estimate the oral uptake efficiency
      of pollutants in mammals for compounds over a wide K(ow) range with an emphasis
      on hydrophilic compounds, i.e. compounds in the lower K(ow) range. Usually, most
      models use octanol as a single surrogate for the membrane and thus neglect the
      bilayer structure of the membrane. However, compounds with polar groups can have
      different affinities for the different membrane regions. Therefore, an existing
      bioaccumulation model was extended by dividing the diffusion resistance through
      the membrane into an outer and inner membrane resistance, where the solvents
      octanol and heptane were used as surrogates for these membrane regions,
      respectively. The model was calibrated with uptake efficiencies of environmental
      pollutants measured in different mammals during feeding studies combined with
      human oral uptake efficiencies of pharmaceuticals. The new model estimated the
      uptake efficiency of neutral (RMSE=14.6) and dissociating (RMSE=19.5) compounds
      with logK(ow) ranging from -10 to +8. The inclusion of the K(hw) improved uptake
      estimation for 33% of the hydrophilic compounds (logK(ow)<0) (r(2)=0.51,
      RMSE=22.8) compared with the model based on K(ow) only (r(2)=0.05, RMSE=34.9),
      while hydrophobic compounds (logK(ow)>0) were estimated equally by both model
      versions with RMSE=15.2 (K(ow)&K(hw)) and RMSE=15.7 (K(ow) only). The model can
      be used to estimate the oral uptake efficiency for both hydrophilic and
      hydrophobic compounds.

PMID- 23147569
TI  - Vorinostat, an HDAC inhibitor attenuates epidermoid squamous cell carcinoma
      growth by dampening mTOR signaling pathway in a human xenograft murine model.
AB  - Histone deacetylase (HDAC) inhibitors are potent anticancer agents and show
      efficacy against various human neoplasms. Vorinostat is a potent HDAC inhibitor
      and has shown potential to inhibit growth of human xenograft tumors. However, its
      effect on the growth of skin neoplasm remains undefined. In this study, we show
      that vorinostat (2 MUM) reduced expression of HDAC1, 2, 3, and 7 in epidermoid
      carcinoma A431 cells. Consistently, it increased acetylation of histone H3 and
      p53. Vorinostat (100mg/kg body weight, IP) treatment reduced human xenograft
      tumor growth in highly immunosuppressed nu/nu mice. Histologically, the
      vorinostat-treated tumor showed features of well-differentiation with large
      necrotic areas. Based on proliferating cell nuclear antigen (PCNA) staining and
      expression of cyclins D1, D2, E, and A, vorinostat seems to impair proliferation
      by down-regulating the expression of these proteins. However, it also induced
      apoptosis. The mechanism by which vorinostat blocks proliferation and makes tumor
      cells prone to apoptosis, involved inhibition of mTOR signaling which was
      accompanied by reduction in cell survival AKT and extracellular-signal regulated
      kinase (ERK) signaling pathways. Our data provide a novel mechanism-based
      therapeutic intervention for cutaneous squamous cell carcinoma (SCC). Vorinostat
      may be utilized to cure skin neoplasms in organ transplant recipient (OTR). These
      patients have high morbidity and surgical removal of these lesions which
      frequently develop in these patients, is difficult.

PMID- 23147572
TI  - The multi-functional roles of GNMT in toxicology and cancer.
AB  - Although glycine N-methyltransferase (GNMT) has been discovered for five decades,
      its function was not elucidated until recently. In this review, we discuss the
      multiple roles of GNMT in toxicology and cancer. Besides catalyzing the
      production of methylglycine (sarcosine) in one carbon metabolism pathway, GNMT
      was found to be able to bind a number of polycyclic aromatic hydrocarbons and
      inhibit DNA adducts formation. Moreover, GNMT exerts protective effects against
      the cytotoxicity and carcinogenicity of benzo(a)pyrene and aflatoxin B(1) in
      vitro and in vivo. Occupational study showed that workers who had genotypes with
      higher GNMT promoter activity may have lower content of oxidative damaged DNA
      products in their urine. In terms of cancer, recent studies using GNMT knockout
      mouse models demonstrated that GNMT deficiency has high penetrance in inducing
      the development of steatohepatitis and hepatocellular carcinoma. In terms of the
      mechanism, besides dysregulation of epigenetic modification, insights have been
      provided by recent identification of two novel proteins interacting with GNMT
      DEPTOR and NPC2. These studies suggest that GNMT not only is involved in mTOR
      signaling pathway, but also plays an important role in the intracellular
      trafficking of cholesterol. The implication of these findings to the preventive
      medicine and translational research will be discussed.

PMID- 23147571
TI  - The targeted inhibition of mitochondrial Hsp90 overcomes the apoptosis resistance
      conferred by Bcl-2 in Hep3B cells via necroptosis.
AB  - Previous studies have reported that a Gamitrinib variant containing
      triphenylphosphonium (G-TPP) binds to mitochondrial Hsp90 and rapidly inhibits
      its activity, thus inducing the apoptotic pathway in the cells. Accordingly, G
      TPP shows a potential as a promising drug for the treatment of cancer. A cell can
      die from different types of cell death such as apoptosis, necrosis, necroptosis,
      and autophagic cell death. In this study, we further investigated the mechanisms
      and modes of cell death in the G-TPP-treated Hep3B and U937 cell lines. We
      discovered that G-TPP kills the U937 cells through the apoptotic pathway and the
      overexpression of Bcl-2 significantly inhibits U937 cell death to G-TPP. We
      further discovered that G-TPP kills the Hep3B cells by activating necroptosis in
      combination with the partial activation of caspase-dependent apoptosis.
      Importantly, G-TPP overcomes the apoptosis resistance conferred by Bcl-2 in Hep3B
      cells via necroptosis. We also observed that G-TPP induces compensatory autophagy
      in the Hep3B cell line. We further found that whereas there is a Bcl-2-Beclin 1
      interaction in response to G-TPP, silencing the beclin 1 gene failed to block LC3
      II accumulation in the Hep3B cells, indicating that G-TPP triggers Beclin 1
      independent protective autophagy in Hep3B cells. Taken together, these data
      reveal that G-TPP induces cell death through a combination of death pathways,
      including necroptosis and apoptosis, and overcomes the apoptosis resistance
      conferred by Bcl-2 in Hep3B cells via necroptosis. These findings are important
      for the therapeutic exploitation of necroptosis as an alternative cell death
      program to bypass the resistance to apoptosis.

PMID- 23147573
TI  - Gold versus silver catalyzed intramolecular hydroarylation reactions of [(3
      arylprop-2-ynyl)oxy]benzene derivatives.
AB  - The scope and the generality of gold versus silver catalyzed intramolecular
      hydroarylation reactions of 3-[(3-arylprop-2-ynyl)oxy]benzene derivatives in
      terms of rings substitution were investigated. Only products deriving from 6-endo
      cyclization were exclusively formed. The features of substituents had a
      considerable effect on the reaction outcome in the presence of silver catalysis,
      whereas gold catalysis revealed a unique blend of reactivity and selectivity and
      represented the only choice for the intramolecular hydroarylation reaction of the
      starting substrates bearing electron deficient arenes.

PMID- 23147575
TI  - Obesity: Fat from plastics? Linking bisphenol A exposure and obesity.

PMID- 23147577
TI  - Diabetes: long-acting insulin analogues--are benefits worth the cost?

PMID- 23147581
TI  - Surgery: the coming of age of metabolic surgery.

PMID- 23147574
TI  - The role of osteocalcin in human glucose metabolism: marker or mediator?
AB  - Increasing evidence supports an association between the skeleton and energy
      metabolism. These interactions are mediated by a variety of hormones, cytokines
      and nutrients. Here, the evidence for a role of osteocalcin in the regulation of
      glucose metabolism in humans is reviewed. Osteocalcin is a bone matrix protein
      that regulates hydroxyapatite size and shape through its vitamin-K-dependent,
      gamma-carboxylated form. The concentration of osteocalcin in the circulation is a
      measure of bone formation. The undercarboxylated form of osteocalcin is active in
      glucose metabolism in mice. Total serum osteocalcin concentrations in humans are
      inversely associated with measures of glucose metabolism; however, human data are
      inconclusive with regard to the role of uncarboxylated osteocalcin in glucose
      metabolism because most studies do not account for the influence of vitamin K on
      the proportion of undercarboxylated osteocalcin or differentiate between the
      total and uncarboxylated forms of osteocalcin. Furthermore, most human studies do
      not concomitantly measure other bone turnover markers to isolate the role of
      osteocalcin as a measure of bone formation from its effect on glucose metabolism.
      Carefully designed studies are required to define the role of osteocalcin and its
      carboxylated or undercarboxylated forms in the regulation of glucose metabolism
      in humans.

PMID- 23147582
TI  - Diabetes: O-GlcNAcylation--a new diagnostic tool for type 2 diabetes mellitus?

PMID- 23147583
TI  - Epidemiology: lipid level trends improving in USA.

PMID- 23147584
TI  - Thyroid function: functional thyroid gland grown in vitro offers intriguing
      therapeutic possibility.

PMID- 23147585
TI  - Paediatrics: Cognitive benefits of tight glucose control in critically ill
      children.

PMID- 23147586
TI  - Obesity: novel melanocortin 4 receptor agonist causes weight loss in obese rhesus
      macaques.

PMID- 23147587
TI  - Obesity: High teenage BMI increases ESRD risk.

PMID- 23147589
TI  - Parathyroid gland: complications of HPT.

PMID- 23147593
TI  - Nutrition: Consumption of legumes might be beneficial in type 2 diabetes
      mellitus.

PMID- 23147591
TI  - Epidemiology: air pollution and mortality from diabetes mellitus.

PMID- 23147594
TI  - Removal of large or giant sporadic vestibular schwannomas via translabyrinthine
      approach: a report of 115 cases.
AB  - BACKGROUND/AIMS: The present study was a retrospective analysis of surgical
      outcomes of large or giant vestibular schwannomas (VSs) via a translabyrinthine
      approach (TLA). METHODS: One hundred and fifteen sporadic large or giant VSs
      (maximal diameter in the cerebellopontine angle >=31 mm) were operated via TLA
      between January 2001 and December 2010. We divided patients into two groups:
      cystic VS (CVS) and solid VS (SVS) group. The surgical outcomes were recorded and
      compared. RESULTS: Total, near total, and subtotal tumor removal rate was 89.6,
      7.8, and 2.6%, respectively. The near total removal rate in CVS was higher than
      that in SVS (16.7 vs. 3.8%). The anatomical facial nerve (FN) integrity was
      preserved in 101 patients (87.8%). More FNs in CVS were interrupted (22.2%).
      There were 29.6, 56.5, and 13.9% of patients who had a short-term (1 month) FN
      function of House-Brackmann grade I or II, III or IV, and V or VI, respectively.
      The CVS had worse FN function than the SVS group. The mortality rate was 0.9%.
      Cerebrospinal fluid leakage occurred in 8 patients (7.0%). Four (3.5%) patients
      had recurrence. CONCLUSIONS: Cyst formation is a crucial factor for surgical
      outcome of VS. With near total or subtotal tumor removal, worse functional
      outcomes in large or giant CVSs should be foreseen.

PMID- 23147595
TI  - Statins, autophagy and cancer metastasis.
AB  - Statins inhibit 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase. They
      are traditionally considered to be cholesterol-lowering agents, but in recent
      years more and more effects of statins have been revealed, including anti
      inflammation, immunomodulation, neuroprotection, improvement of bone metabolism,
      and antitumour effects. In the past few years, extensive studies have shown that
      statins can induce autophagy in tumour cells as well as in some normal cells, and
      autophagy may be involved in the regulation of cancer metastasis. This review is
      focused on summarising and discussing the relationships among statins, autophagy
      and cancer metastasis. Studies showed that activation of the AMPK-TOR signalling
      pathway may be a major mechanism of statin-induced autophagy. Depleting cellular
      geranylgeranyl diphosphate activates AMPK and inactivates TOR, leading to
      autophagic responses. Autophagy, a strategy of self-adaption, is a double-edged
      sword in tumour metastasis. On one hand, autophagy contributes to anti-metastasis
      activity by, for example, restricting tumour necrosis and inflammatory cell
      infiltration of tumours and promoting the release of high-mobility group box
      protein 1 that triggers strong antitumour immune responses. On the other hand, it
      also exhibits a pro-metastasis activity. In summary, we propose a working
      hypothesis: statins induce autophagy in cancer cells, and this constitutes, at
      least in part, the basis for the anti-metastatic effect of statins. The idea that
      autophagy is responsible for statin-induced anti-metastasis effects is probably
      novel, and it extends the conventional view that interference of the post
      translational modification of Rho GTPases by statins prevents tumour metastasis.

PMID- 23147596
TI  - Outcomes of ureteroscopy for stone disease in pregnancy: results from a
      systematic review of the literature.
AB  - INTRODUCTION: Our aim was to evaluate the clinical efficacy and safety of
      ureteroscopy as a primary treatment for pregnant women with symptomatic ureteric
      stones who have failed conservative management. MATERIALS AND METHODS: A
      systematic review of the literature from January 1990 to June 2011 was performed,
      including all English language articles. Outcome measures were clinical efficacy,
      in terms of stone clearance and need for additional procedures, and safety in
      terms of complications. RESULTS: A total of 239 abstracts were screened and 15
      studies were identified reporting on 116 procedures. The surgical methods of
      stone management employed were stone extraction with basket only (n = 55, 47%),
      laser fragmentation (n = 27, 23%; holmium, n = 20, pulse dye, n = 7), impact
      lithotripsy (n = 21, 18%), ureteroscopic lithotripsy (n = 6, 5%) and a
      combination of methods (n = 6, 5%). A post-operative stent was inserted in 64 of
      116 procedures (55%). Complete stone clearance was seen in 100 of the 116
      procedures (86%). There were 2 major complications (1 ureteral perforation and 1
      case of premature uterine contraction) and 7 minor complications (5 urinary tract
      infections and 2 cases of post-operative pain). CONCLUSION: This review suggests
      that stone clearance using ureteroscopy is a relatively safe option in pregnancy
      with a high success rate.

PMID- 23147597
TI  - Tetrabutylammonium iodide catalyzed allylic sulfonylation of alpha-methyl styrene
      derivatives with sulfonylhydrazides.
AB  - Sulfonyl radicals generated from sulfonylhydrazides by the Bu(4)NI-tert-butyl
      hydroperoxide (TBHP) catalysis system underwent addition to a variety of alpha
      methyl styrene derivatives to give the corresponding allylic sulfones. This
      selective allylic sulfonylation is metal-free, operationally simple, and
      environmentally friendly.

PMID- 23147598
TI  - Advanced treatments for childhood epilepsy: beyond antiseizure medications.
AB  - A substantial minority of children with epilepsy have continued seizures despite
      adequate trials of standard antiseizure medications. To maximize seizure control
      and thereby optimize their neurodevelopmental outcomes, alternate nonmedication
      therapies should be considered for these patients. Dietary therapies, including
      the ketogenic diet and its variations, have been available for years. With a
      recent resurgence in popularity and expansion of indications, these treatments
      can lead to freedom from seizures or a significantly reduced seizure burden for a
      large number of patients. For carefully selected individuals, resective epilepsy
      surgery may offer the best hope for a cure. For others, palliation may be
      achieved through additional surgical approaches, such as corpus callosotomy and
      multiple subpial transections, or through neurostimulation techniques, such as
      the vagus nerve stimulator. In this review, we present these nonmedication
      approaches to treatment-resistant childhood epilepsy, with attention to patient
      selection and the potential risks and benefits.

PMID- 23147599
TI  - Relationship between pediatric blood and marrow transplant center volume and day
      +100 mortality: Pediatric Blood and Marrow Transplant Consortium experience.
AB  - The number of patients receiving a BMT is currently being used as a factor in the
      accreditation process in determining whether a center can provide a high-quality
      BMT. Such criteria particularly impact pediatric BMT centers as most of them
      perform a relatively small number of BMTs. To determine whether patient volume is
      a valid marker of pediatric BMT center's capabilities, the Pediatric Blood and
      Marrow Transplant Consortium (PBMTC) evaluated data from its registry to define
      the relationship between a pediatric transplant center's patient volume and day
      +100 mortality. The analyses evaluated 2575 transplants from 60 centers reporting
      to the PBMTC between the years 2002 and 2004. The volume-outcome relationship was
      evaluated while adjusting for 46 independent data categories divided between nine
      variables that were known- or suspected-mortality risk factors. We found no
      association between transplant center volume and day +100 mortality in several
      analyses. A calculated intraclass correlation coefficient also indicated that
      differences in individual transplant center volume contributed to only 1% of the
      variance in day +100 mortality within the PBMTC. The results of this study
      suggest that factors other than transplant center volume contribute to variation
      in day +100 mortality among pediatric patients.

PMID- 23147600
TI  - [Legionnaires disease (legionella pneumonia)].

PMID- 23147602
TI  - [What is your diagnosis? Spontaneous umbilical rupture in decompensated liver
      cirrhosis].

PMID- 23147603
TI  - [Current aspects of obstetric ultrasound in the screening setting].
AB  - Screening ultrasound during pregnancy has an established role and a defined scope
      that has increased over the years. Diagnostic possibilities with newer ultrasound
      systems can help in particular in referral settings and for a more detailed
      analysis of various fetal organ systems. In particular for the fetal heart there
      is a clear benefit with regard to neonatal morbidity and mortality.

PMID- 23147604
TI  - [Lung function testing in private practice].
AB  - According to the international guidelines of COPD (GOLD) and asthma (GINA)
      diagnosis and treatment of both diseases necessitate spirometry in the private
      practice as well as in hospital setting. However today, spirometry is not
      sufficiently used in Switzerland. This paper intends to give an easy overview how
      spirometry is performed and spirometric values can be interpreted.

PMID- 23147605
TI  - [Diabetic, neuropathic, arteriopathic foot and dressing choice].
AB  - The definition for the diabetic foot is infection, ulceration or destruction of
      deep tissues of the foot associated with neuropathy or peripheral vascular
      disease in the lower extremity of people with diabetes. Non-diabetic patients may
      suffer the same risks when neuropathy and arteriopathy are present. Knowing that
      85% of amputations are preceded by foot ulcers, prevention is primordial. At the
      onset of an ulcer, immediate treatment must be undertaken and preferably by an
      interdisciplinary team. Delayed healing and increased risk of infection are often
      due to an associated vascular disease. While the array of dressings is expansive
      there is no "gold standard" treatment or "miracle dressing" described for foot
      ulcers. The management consists of wound analysis, debridement, woundcare  and
      especially offloading.

PMID- 23147606
TI  - [Blood in the diaper].

PMID- 23147607
TI  - [The head-up-orthosis - a good solution for ambulant patients with Dropped-head
      syndrome].
AB  - Severe paresis of the neck muscles, dystonia or an increased activation of the
      head flexor can lead to dropped-head syndrome. It can be based on various
      neurological diseases. We present a patient with amyotrophic lateral sclerosis
      with severe paresis of the head extensor muscles, which led to a dropped-head
      syndrome. Usual advices did not permit an adequate swallowing and breathing. The
      new developed device (head-up) can be adjusted on the individual needs which lead
      to a marked improvement in quality of life of the patient. Especially for
      ambulatory patients with Dropped-head syndrome is the "head-up" a very good
      solution.

PMID- 23147608
TI  - [Benefit and side effects of urinary incontinence drug therapy in women].

PMID- 23147609
TI  - [HIV rapid self test: saliva or blood?].

PMID- 23147611
TI  - [Abnormal P spikes. CME EKG 39. Physiologic Wenckebach behavior of the
      atrioventricular node].

PMID- 23147614
TI  - Does vascular burden contribute to the progression of mild cognitive impairment
      to dementia?
AB  - AIMS: To investigate the contribution of vascular risk factors (VRFs), vascular
      diseases (VDs) and white matter lesions (WMLs) to the progression of mild
      cognitive impairment (MCI) to dementia and Alzheimer's disease (AD). METHODS: Two
      hundred forty-five consecutive subjects with MCI (age 74.09 +/- 6.92 years) were
      followed for an average of 2.4 years. The Hachinski Ischemic Score and the
      Framingham Stroke Risk Profile were used to summarize VRFs and VDs. WMLs were
      graded using the Age-Related White Matter Changes Scale. RESULTS: One hundred
      twenty-nine (52.6%) out of 245 subjects at risk converted to dementia, including
      87 cases of AD. When hypertension occurred in MCI with deep WMLs, a 1.8-fold
      increased risk of dementia was observed (95% CI = 1.0-3.4). When deep WMLs
      occurred in MCI with high scores (>=4) on the Hachinski scale, a 3.5-fold (95% CI
      = 1.6-7.4) and 3.8-fold (95% CI = 1.2-11.5) risk of progression to dementia and
      AD was observed, respectively. Analogously, the joint effect of WMLs and high
      scores (>=14) on the Framingham scale nearly doubled the risk of dementia (hazard
      ratio = 1.9, 95% CI = 1.1-3.3). CONCLUSIONS: Accelerated progression of MCI to
      dementia and AD is to be expected when VRFs and VDs occur together with WMLs.

PMID- 23147615
TI  - Tibial tubercle fractures: complications, classification, and the need for intra
      articular assessment.
AB  - BACKGROUND: Adolescent tibial tubercle fractures are uncommon, complex, high
      energy injuries. The use of lateral radiographs in isolation to diagnose and
      treat these injuries is the standard of practice. However, with a single 2
      dimensional (2D) view, there may be a risk that the degree of injury can be
      underestimated. This study was performed to report on the outcomes of tibial
      tubercle fractures operatively treated, determine the utility of a single lateral
      x-ray to accurately document injury severity and pattern, delineate the role of
      advanced imaging and intraoperative arthroscopy/arthrotomy in injury treatment,
      and propose a new classification system of tibial tubercle fractures that
      accounts for the complex 3D nature of proximal tibial physeal closure, and
      recognizes the importance of intra-articular extension, providing guidance for
      intervention. METHODS: A retrospective review of operatively treated tibial
      tubercle fractures at our institution from 2003 to 2010 was performed. Child age,
      weight, mechanism of injury, Ogden classification (x-ray), advanced imaging
      results [computed tomography (CT)/magnetic resonance imaging (MRI)] including
      intra-articular fracture patterns, surgical techniques, intraoperative articular
      findings, and postoperative complications were collected. In addition, we
      classified all of our patients into a new classification system (type A--tubercle
      youth, type B--physeal, type C--intra-articular, type D--tubercle teen) based on
      a combination of plain radiograph (anteroposterior and lateral), advanced imaging
      (CT/MRI), and intraoperative arthrotomy/arthroscopy findings. RESULTS: We found
      41 tibial tubercle fractures in 40 children (all of whom were male) with a mean
      age of 15.0 +/- 1.1 years, and mean weight of 80.3 +/- 23.4 kg. Injuries mostly
      occurred during jumping activities. At initial presentation, compartment syndrome
      or vascular compromise was seen in nearly 10% of patients, all of whom had type B
      -physeal injuries under our new classification system. Fifty percent of injuries
      were underestimated and/or not appreciated by lateral x-ray alone. In patients
      with intra-articular involvement, consistent 3D fracture patterns were seen on CT
      including anterior fragments (sagittal plane), lateral fragments (coronal plane),
      and anterolateral fragments (axial plane). Our new 4 part classification system
      was able to classify all fractures: type A (2 patients, mean age, 12.7 +/- 0.2
      y), type B (13 patients, mean age, 14.8 +/- 0.7 y), type C (22 patients, mean
      age, 15.3 +/- 1.1 y), and type D (2 patients, mean age, 15.5 +/- 0.1 y). All
      fractures achieved radiographic union with 2 patients (type A--tubercle youth and
      type B--physeal) requiring additional procedures due to premature physeal
      closure. CONCLUSIONS: Tibial tubercle fractures represent high-energy injuries
      with potentially devastating complications such as compartment syndrome and/or
      vascular compromise. Intra-articular involvement is often missed with the use of
      plain x-ray and drastically underestimates injury severity. The use of
      preoperative CT scan or MRI should be utilized as adjunct to plain lateral
      radiograph. If intra-articular involvement is recognized preoperatively,
      arthroscopy or open arthrotomy should be utilized at the time of surgery. Our new
      classification system is rooted in the development of the proximal tibia,
      accounts for intra-articular involvement, and provides guidance for treatment.
      LEVEL OF EVIDENCE: Level III--diagnostic study.

PMID- 23147616
TI  - MRI findings in adolescent patients with acute traumatic knee hemarthrosis.
AB  - BACKGROUND: Physical examination may be inconclusive in adolescents presenting
      with an acute traumatic knee effusion because of pain and guarding. The purpose
      of this study was to describe the magnetic resonance imaging (MRI) findings in
      adolescents with traumatic knee effusions and to compare injuries based on age,
      sex, and physeal maturity. METHODS: All MRIs using a knee trauma protocol
      performed at our institution over a 2-year period were evaluated. One hundred
      thirty-one patients between the ages of 10 to 18 years of age with a clinical
      history of acute knee trauma and an effusion confirmed on MRI met our study
      inclusion criteria. They were divided into 2 age groups: 10 to 14 and 15 to 18
      years old. Pathology was confirmed using clinical history, MRI, and any available
      surgical reports. RESULTS: Of the 131 patients with an acute knee effusion, there
      were 59 patients in the younger group (10 to 14 y old) and 72 patients in the
      older group (15 to 18 y old). In the younger group, patellar dislocations (36%),
      anterior cruciate ligament (ACL) tears (22%), and isolated meniscus tears (15%)
      were the most common injuries. In the older group, ACL tears (40%), patellar
      dislocations (28%), and isolated meniscus tears (13%) were the most common
      injuries. ACL injuries represented 28% of injuries in males and 38% of injuries
      in females, whereas patellar dislocations represented 28% of injuries in males
      and 37% of injuries in females. There was a trend toward adolescents with active
      growth plates sustaining more patellar dislocations and adolescents with closed
      growth plates sustaining more ACL injuries. Forty-one percent of patients in this
      study underwent surgery. CONCLUSIONS: Patellar dislocation is a common injury in
      children who present with a traumatic knee effusion, especially in young
      adolescents and females. Adolescents presenting with a traumatic knee effusion
      should undergo MRI because of the high rate of positive findings missed by
      physical examination and plain radiographs that may warrant surgical repair or
      reconstruction. LEVEL OF EVIDENCE: Level III.

PMID- 23147617
TI  - Accuracy of 3-Tesla magnetic resonance imaging for the diagnosis of intra
      articular knee injuries in children and teenagers.
AB  - BACKGROUND: Magnetic resonance imaging (MRI) is a commonly used tool for the
      diagnosis of intra-articular knee pathologies. Although many studies have
      reported the accuracy of MRI in the adult population, fewer studies have
      investigated these tests in younger patients. Furthermore, these studies have
      shown a higher variability in both the sensitivity and the specificity of MRI for
      these knee injuries in this age group. Advancements in MRI technology, such as
      the 3-Tesla (3T) MRI magnet, have shown promising results for musculoskeletal
      injury diagnosis in adults. This study aims to evaluate 3 T MRI for the diagnosis
      of intra-articular knee pathologies in a pediatric and adolescent patient
      population. METHODS: The records of 116 patients (119 knees) under the age of 20
      years who underwent 3 T MRI studies of the knee and subsequent knee arthroscopy
      were reviewed retrospectively. The MRI report from the musculoskeletal radiology
      staff, the interpretation from the staff orthopedic surgeon, and the operative
      note dictations were compared, with a focus on meniscus and anterior cruciate
      ligament (ACL) pathologies. Seventeen orthopedic staff reads were not obtainable.
      Arthroscopy was used as the gold standard for diagnosis. RESULTS: The average age
      at MRI exam was 16.0 years and at surgery was 16.2 years. Using the
      musculoskeletal radiologist interpretation, the sensitivity and the specificity
      of 3 T MRI were 81.0% and 90.9% for medial meniscus injuries, 68.8% and 93% for
      lateral meniscus injuries, and 97.9% and 98.6% for ACL injuries, respectively.
      The orthopedic surgeon's interpretation of 3 T MRI had a sensitivity and
      specificity of 75.7% and 92.4% for medial meniscus injuries, 69.8% and 98.3% for
      lateral meniscus injuries, and 100% and 98.6% for ACL injuries, respectively.
      Posterior horn tears had the greatest discrepancies. CONCLUSIONS: When performed
      on pediatric and adolescent patients, newer 3 T MRI studies have excellent
      accuracy for diagnosing ACL tears. These studies also show a higher accuracy for
      the diagnosis of medial meniscal tears than lateral meniscal tears. LEVEL OF
      EVIDENCE: Diagnostic study--Level 2.

PMID- 23147618
TI  - Immediate intramedullary flexible nailing of open pediatric tibial shaft
      fractures.
AB  - BACKGROUND: Flexible nailing has become the preferred implant for pediatric
      patients with tibial shaft fractures that require operative fixation. Immediate
      definitive fracture fixation with flexible nails in patients with high-energy,
      open fractures has not been examined. The purpose of our study was to determine
      if immediate flexible nailing of open pediatric tibial shaft fractures is safe
      and efficacious from a bone healing, wound, and infectious standpoint. METHODS: A
      retrospective review of 26 tibial shaft fractures consecutively treated with
      flexible nailing at our institution from 2003 to 2010 was performed. Age,
      mechanism of injury, associated injuries, presence of compartment syndrome,
      antibiotic administration, systemic insults, time to union, as well as bone
      healing (nonunion, delayed union, malunion, leg length discrepancy, growth
      arrest), wound, and infectious complications were collected. Comparisons were
      made between patients with open fractures and those with closed fractures.
      RESULTS: We identified 14 patients with open fractures and a control group of 12
      patients with closed injuries who underwent flexible nailing. Patients with open
      fractures were more likely to have polytraumatic injuries (71.0% vs. 25.0%, P =
      0.04). There was no difference (P = 1.0) in the rates of compartment syndrome
      (open = 14.0%, closed = 17.0%) between the 2 groups. Systemic complications
      (pulmonary compromise and increased intracranial pressure) were noted in 2
      patients who underwent immediate nailing of their open fractures; both of whom
      had closed head injuries. There was no difference (P = 1.0) in the rates of
      wound/infectious complications between the open (7.0%) and closed (4.0%)
      fractures groups, with no cases of wound breakdown or osteomyelitis. There was an
      increased rate (P = 0.02) of bone healing complications in the open fracture
      group (21.0% vs. 4.0%); all in patients with Gustilo type 2 or 3 injuries. All
      patients achieved radiographic union at final follow-up. CONCLUSIONS: Immediate
      flexible nailing of open pediatric tibial shaft fractures can be safely performed
      with minimal risk of wound or infectious complications. Clinicians should
      understand that prolonged bone healing (particularly in Gustilo type 2 or 3
      injuries) should be expected in patients who undergo immediate flexible nailing
      of their open fractures. Open tibial shaft fractures are high-energy injuries,
      and should be seen as surrogate markers of polytrauma in the pediatric
      population. The risk of compartment syndrome is high regardless of whether a
      patient has a closed or open tibia fracture, and caution should be used in
      performing flexible nailing in patients who may have closed head injury due to a
      risk of systemic complications. LEVEL OF EVIDENCE: Level III, therapeutic study,
      retrospective cohort.

PMID- 23147619
TI  - Locked intramedullary nailing in the treatment of femoral shaft fractures in
      children younger than 12 years of age:  indications and preliminary report of
      outcomes.
AB  - BACKGROUND: Although flexible intramedullary nailing is a popular treatment
      option for femoral shaft fractures in juvenile and young adolescent patients, it
      may not be appropriate in some patients because of patient size and/or fracture
      configuration. METHODS: Retrospective review over a 3-year period identified 17
      skeletally immature patients (18 fractures) with femoral shaft fractures treated
      with noncannulated rigid locked intramedullary nailing because of a length
      unstable fracture or patient overweight or obesity. The 14 males and 3 females
      had an average age of 10 years at the time of injury (range, 7.6 to 11.9 y).
      Their average weight was 38.3 kg (range, 22.7 to 52 kg), with an average body
      mass index of 18.9 (range, 13.9 to 26.9). RESULTS: All fractures united at an
      average of 13 weeks, with no osteonecrosis, malalignment, malunion, or hardware
      failure. CONCLUSIONS: Preliminary results suggest that noncannulated, rigid,
      locked intramedullary nails can be used safely and effectively for selective
      fixation of femoral shaft fractures in skeletally immature patients younger than
      12 years of age. LEVEL OF EVIDENCE: Level IV.

PMID- 23147620
TI  - Arthroscopic stabilization for voluntary shoulder instability.
AB  - BACKGROUND: Voluntary shoulder instability is characterized by a patient's
      ability to sublux their shoulder using selective muscle contraction and
      relaxation. High failure rates exist with open shoulder stabilization in this
      group of patients. The purpose of this study was to report the outcomes for
      patients with voluntary instability treated arthroscopically. METHODS: All
      patients with voluntary instability from 2006 to 2008 treated with arthroscopic
      stabilization were included. All patients had documentation of preoperative and
      postoperative American Shoulder and Elbow Surgeons (ASES) questionnaire score,
      visual analogue scale of pain, simple shoulder test, and range of motion.
      Subjective satisfaction and return to sport was also determined. RESULTS: Ten
      patients were identified for inclusion in the study. The average age of the 5
      male and 5 female patients was 16.2 +/- 2.33 years. Average clinical follow-up
      period was 31 +/- 6.5 months. Visual analogue scale scores improved from 5.33 +/-
      3.50 preoperatively to 1.44 +/- 2.0 postoperatively, ASES scores improved from
      52.2 +/- 18.7 to 85.9 +/- 14.9 and simple shoulder test improved from 8.17 +/-
      3.19 to 11.4 +/- 1.01. All of the functional evaluation scores improved
      postoperatively (P < 0.05). There was no case of postoperative dislocation or
      subluxation, all reported excellent subjective outcome, and all those who played
      sports returned to their previous level. CONCLUSIONS: Good and excellent outcomes
      can be obtained with arthroscopic stabilization for patients with voluntary
      instability. Improved results from previous reports may be related to improved
      patient selection, surgical technique, and postoperative rehabilitation. Although
      long-term follow-up and comparative studies are necessary, arthroscopic
      stabilization seems to be an acceptable treatment option for patients who fail
      nonoperative treatment. LEVEL OF EVIDENCE: Level IV, case series, retrospective
      review.

PMID- 23147621
TI  - Redefining the cast index:  the optimum technique to reduce redisplacement in
      pediatric distal forearm fractures.
AB  - BACKGROUND: The aim of this study was to identify the optimal cast index (CI)
      level that reduces the risk of fracture redisplacement. The CI is the ratio of
      sagittal to coronal width from the inside edges of the cast at the fracture site.
      Previous studies have used 0.7 as the standard. METHODS: Case records and
      radiographs of 1001 children who underwent a manipulation under anesthesia for a
      displaced fracture of the distal forearm were studied. Redisplacement was defined
      as > 15 degrees of angulation and/or > 80% of translational displacement on check
      radiographs at 2 weeks. Angulation (degrees) and translational displacement (%)
      were measured on the initial and check radiographs. The CI was measured on the
      check radiographs. The CI has previously been validated in an experimental study.
      RESULTS: The adequacy of reduction after manipulation was determined by
      translation and angulation of the radius and ulna in anteroposterior and lateral
      plain film radiographs. From the 1001 patients who qualified for the study,
      fracture redisplacement was seen in 107 (10.6%) cases at the 2-week follow-up. A
      total of 752 (75%) patients had CIs of <= 0.8, whereas 249 (25%) had casting
      indices of >= 0.81. In patients with CIs of <= 0.8, the displacement rate was
      only 5.58%. However, in patients with CIs of >= 0.81, the displacement rate was
      26%. A high CI was the sole factor that was significantly higher in the
      redisplacement group. No statistically significant difference was seen for age,
      sex, or surgeon seniority. Statistical differences were not noted in initial
      angular deformity or initial displacement. DISCUSSION: The CI is a simple
      reliable radiographic measurement to predict the redisplacement of forearm
      fractures in children. A plaster with a CI of > 0.81 is prone to redisplacement.
      High CIs are associated with redisplacement of fractures and should be avoided
      when molding casts in distal forearm fractures. LEVELS OF EVIDENCE: Level III-
      retrospective comparative study.

PMID- 23147622
TI  - Outcome assessment in neuromuscular spinal deformity.
AB  - Patient-based outcome measures are important tools quantifying the disease
      specific and/or global quality of life (QOL) effects of spinal deformity
      treatment. In patients with neuromuscular disorders such as cerebral palsy,
      muscular dystrophy, and myelomeningocele, treatment effects must be
      differentiated from underlying disease functional impairments. In general, the
      goals of spinal surgery in these patients are to improve QOL by enhancing sitting
      balance and posture, improving lung and gastrointestinal function, and reducing
      pain and deformity. In selected patients, improving ambulation and hand function
      may also be realistic surgical goals. QOL measures specific to both the
      neuromuscular diagnosis and spinal deformity provide higher quality information
      on treatment outcomes for a particular patient than standard radiographic
      measures. This article reviews patient-based outcome measures in spinal deformity
      patients with neuromuscular disorders, including their development and use in
      comparative outcome studies in the recent literature.

PMID- 23147623
TI  - Pain management in patients with adolescent idiopathic scoliosis undergoing
      posterior spinal fusion: combined intrathecal morphine and continuous epidural
      versus PCA.
AB  - STUDY DESIGN: A retrospective case-comparison study. OBJECTIVE: Compare efficacy
      and safety of combined intrathecal morphine (ITM) and epidural analgesia (EPI) to
      that of conventional intravenous patient-controlled analgesia (IV-PCA) after
      posterior spinal fusion (PSF) for adolescent idiopathic scoliosis (AIS). SUMMARY
      OF BACKGROUND DATA: Pain control after PSF in AIS has been managed traditionally
      with IV-PCA. More recently studies have shown improvement in pain control with
      the use of continuous EPI or intraoperative ITM. No studies to our knowledge have
      compared the use of both ITM and EPI analgesia to that of IV-PCA. METHODS: An
      Institutional Review Board-approved retrospective case-comparison study was
      performed from 1989 to 2009 of all patients undergoing PSF for AIS. Patients
      received either IV-PCA or ITM/EPI. Daily pain scores were recorded along with
      total opioid and benzodiazepine use. Adverse events were recorded for all the
      patients. RESULTS: A total of 146 patients were initially included in the study;
      95 patients received ITM/EPI and 51 received IV-PCA as a historical control.
      Eight patients from the ITM/EPI group were excluded from the pain comparison
      portion of the study. There were no statistical differences in age, sex, weight,
      or hospital stay between the 2 groups. The ITM/EPI group had, on average, 1
      additional level of fusion (P = 0.001). Daily average pain scores were lower in
      the ITM/EPI group on all hospital days, and statistically lower in days 1 and 3
      to 5. Total opioid requirement was significantly lower in the ITM/EPI patients,
      although oral opioid use was higher among this group. Total benzodiazepine use
      was lower among the IV-PCA group. A total of 15.7% of the IV-PCA patients had
      bladder hypotonia, compared with 1.1% of the ITM/EPI group (P = 0.002). The rate
      of illeus was 15.7% in the IV-PCA patients and 5.7% in the ITM/EPI (P = 0.071).
      Respiratory depression was reported in 4 ITM/EPI patients, 0 in our PCA group.
      Technical catheter malfunction was reported in 8.5% of the EPI group.
      CONCLUSIONS: The use of ITM/EPI after PSF for AIS is safe and effective, this
      methodology provided significantly lower pain scores and lowers total opioid use
      which can lead to urinary and bowel dysfunction.

PMID- 23147624
TI  - Rate of correction after asymmetrical physeal suppression in valgus deformity: 
      analysis using a linear mixed model application.
AB  - BACKGROUND: This study was performed to estimate the rate of angular correction
      after asymmetrical physeal suppression and analyze the factors that influence the
      rate of correction by using a linear mixed model application. METHODS: A total of
      175 physes (72 distal femoral, 70 proximal tibial, and 33 distal tibial) from 78
      consecutive patients with valgus angular deformity of the lower limb who
      underwent asymmetrical physeal suppression were included. The anatomic lateral
      distal femoral angle, the anatomic lateral proximal tibial angle, and the
      anatomic lateral distal tibial angle were measured from the teleroentgenograms of
      the patients' preoperative visit and periodic follow-ups. The rate of angular
      correction was adjusted by multiple factors by using a linear mixed model with
      age, sex, and surgical method as the fixed effects and each subject as the random
      effect. The final model included the age-specific and surgical method-specific
      rate and sex-specific and surgical method-specific intercept. Multivariate
      analysis was performed for this model. RESULTS: In younger children (boys 14 y or
      younger and girls 12 y or younger), the rate of correction of valgus deformity at
      the distal femur, proximal tibia, and distal tibia was 0.71 degrees/month (8.5
      degrees/y), 0.40 degrees/month (4.8 degrees/y), and 0.48 degrees/month (5.8
      degrees/y), respectively. In older children, the rate of correction of valgus
      deformity at the distal femur, proximal tibia, and distal tibia was 0.39
      degrees/month (4.7 degrees/y), 0.29 degrees/month (3.5 degrees/y), and 0.48
      degrees/month (5.8 degrees/y), respectively. The rate of correction at the distal
      femur was significantly lower in older children (P = 0.025). The rate of angular
      correction at the proximal tibia was significantly faster in the screw group than
      in the staple group (P = 0.046). CONCLUSIONS: Asymmetrical physeal suppression
      with staples, percutaneous transphyseal screws, and permanent method all are
      effective methods for treating valgus deformity in growing children. When we
      treat valgus deformity in growing children, we should take into consideration the
      fact that the rate of correction at the distal femur is lower in older children,
      and that at the proximal tibia is faster in the screw group. LEVEL OF EVIDENCE:
      Therapeutic level III.

PMID- 23147625
TI  - Guided growth:  the importance of a single tether. An experimental study.
AB  - BACKGROUND: During the last few years, the use of the 8-plate as a technique for
      hemiepiphysiodesis has gained wide acceptance, as it has been shown that it works
      in a more physiological way than other methods such as staples or transphyseal
      screws. It has mechanically been compared with a tension band plate, and for this
      reason, only a single plate is needed. The following study was undertaken to test
      the 8-plate against the staples and assess factors that can influence the
      difference in results. METHODS: A prospective experimental study was designed to
      compare the ability of 2 hemiepiphysiodesis methods, the 8-plate and the double
      staple, to produce angular deformity in the rabbit's tibia (group I). The
      variable studied was the variations in the articular line-diaphysis angle at 6
      weeks. As the results showed that the 8-plate produced a bigger deformity, a
      second group was designed (group II) comparing single against double staple,
      under the hypothesis that the differences observed in the first group could be
      related to the number of anchors put across the physis and consequently depend on
      the volume of physis involved by the staples. RESULTS: In group I, the 8-plate
      produced a bigger angulation at 6 weeks' time than the 2 staples (a difference of
      6.5 degrees, P = 0.03). Similarly, in group II, the single staple produced a
      greater angulation than the 2 staples (difference 6 degrees, P = 0.08). When both
      groups were compared, no differences in the angulation produced by the 8-plate
      and the single staple with respect to the 2 staples were found. CONCLUSIONS:
      These results suggest that one of the reasons why the 8-plate may act in a more
      "physiological way" (vs. the traditional 2-staple or 3-staple hemiepiphysiodesis)
      could be the fact that the growth plate is tethered only at a single point.
      Therefore, the physis retains a major potential for growth and deformity.
      CLINICAL RELEVANCE: The 8-plate is superior in producing/correcting angular
      deformity when compared with the traditionally used staples (2 or more) but not
      when compared with a single staple.

PMID- 23147626
TI  - Comparison of the calcaneo-cuboid-cuneiform osteotomies and the calcaneal
      lengthening osteotomy in the surgical treatment of symptomatic flexible flatfoot.
AB  - BACKGROUND: Surgery is indicated in symptomatic flatfoot when conservative
      treatment fails to relieve the symptoms. Osteotomies appear to be the best choice
      for these painful feet. The purpose of this study was to compare the clinical and
      radiographic outcome of the calcaneo-cuboid-cuneiform osteotomies (triple C) and
      the calcaneal-lengthening osteotomy in the treatment of children with symptomatic
      flexible flatfoot. METHODS: The surgeries were performed by senior surgeons who
      preferred either triple C or calcaneal lengthening. The results were graded by an
      orthopaedic surgeon uninvolved with the cases. The clinical and radiographic
      outcome was evaluated in 30 feet (21 patients) with a triple C osteotomy and 33
      feet (21 patients) with a calcaneal-lengthening osteotomy. We used the American
      College of Foot and Ankle Surgeons (ACFAS) score (flatfoot module) for clinical
      assessment, which contains a subjective and objective test. We measured and
      compared 12 parameters on the anteroposterior and lateral weight-bearing
      radiographs. The effect of additional procedures (Kidner procedure, medial
      reefing of the talonavicular capsule, tendo-Achilles lengthening, peroneous
      brevis lengthening and, in the calcaneal-lengthening group, a medial cuneiform
      osteotomy) on the clinical and radiographic result was also evaluated. RESULTS:
      Average age at the time of surgery was similar (triple C: 11.2 +/- 3 y, calcaneal
      lengthening: 11.6 +/- 2.5 y, P = 0.51). Average follow-up was 2.7 +/- 2.2 years
      in the triple C group and 5.3 +/- 4 years in the calcaneal-lengthening group.
      There were no significant differences in the clinical outcome measured by the
      ACFAS subjective test in the calcaneal-lengthening group (P = 0.003). There were
      no significant differences in the ACFAS score, both the subjective test (triple
      C: 43.3 +/- 6.1, calcaneal lengthening: 44.7 +/- 7.6, P = 0.52) and the ACFAS
      objective test (triple C: 28.6 +/- 2, calcaneal lengthening: 25.9 +/- 7, P =
      0.13). We found significant differences in 2 of the 12 radiographic measurements:
      anteroposterior talo-first metatarsal angle (triple C: 15.5 +/- 11.1, calcaneal
      lengthening: 7.4 +/- 7.3, P = 0.001) and talonavicular coverage (triple C: 28 +/-
      14.7, calcaneal lengthening: 13.7 +/- 12.4, P<0.001). None of the additional
      procedures improved the clinical outcome. There were 3 (10%) complications in the
      triple C group and 6 (18%) complications in the calcaneal-lengthening group.
      Also, calcaneocuboid subluxation was present in 17 (51.5%) feet of the calcaneal
      lengthening group. CONCLUSIONS: Both techniques obtain good clinical and
      radiographic results in the treatment of symptomatic idiopathic flexible flatfoot
      in a pediatric population. The calcaneal-lengthening osteotomy achieves better
      improvement of the relationship of the navicular to the head of the talus but it
      is associated with more frequent and more severe complications. Additional soft
      tissue procedures have not proven to improve clinical or radiographic results.
      LEVEL OF EVIDENCE: Level III, retrospective comparative study.

PMID- 23147627
TI  - The efficacy of nonsurgical interventions for pediatric flexible flat foot:  a
      critical review.
AB  - BACKGROUND: The pediatric flat foot frequently presents as a common parental
      concern in the health care setting. Foot orthoses are often used, yet benefits
      are uncertain and disputed, having been variably investigated. A recent Cochrane
      review cites limited evidence for nonsurgical interventions. This critical and
      structured review evaluates the effect of pediatric foot orthoses from assessment
      of the current literature. METHODS: A systematic search of the following
      electronic databases: Medline, CINAHL, AMED, and SPORTDiscus, using an array of
      search terms. A further search was also performed on relevant reference listings.
      Inclusion criteria were peer-reviewed journal articles, publication date from
      1970 onwards, in the English language. Exclusion criteria were surgery
      interventions, adult subjects, rigid flat foot, articles based on opinion. A
      structured Quality Index was used to evaluate the research quality of articles.
      Three reviewers independently assessed the studies with disputes resolved by
      majority consensus. Studies were then grouped according to the outcome measures
      used. RESULTS: Thirteen articles, from an initial 429, met the criteria for
      quality evaluation. The mean Quality Index score was 35% (range: 13% to 81%),
      indicative of generally poor and varying methodological quality. CONCLUSIONS: The
      low quality of the studies negates definitive conclusions. Only 3/13 quality
      evaluations scored > 50%; hence, evidence for efficacy of nonsurgical
      interventions for flexible pediatric flat feet is very limited. Future research
      needs validated foot type assessment, applicable outcome measures for the
      intervention, the use of control groups, allowance for independent effects of
      footwear, age range comparisons, larger samples, and prospective, longer follow
      up. CLINICAL RELEVANCE: There is very limited evidence for the efficacy of
      nonsurgical interventions for children with flexible flat feet. Clinicians need
      to consider the lack of good-quality evidence in their decision-making for the
      management of pediatric flat foot.

PMID- 23147628
TI  - Forearm deformities in hereditary multiple exostosis:  clinical and functional
      results at maturity.
AB  - BACKGROUND: Thirty to 60% of hereditary multiple exostoses patients have forearm
      deformities. There is no consensus regarding optimal therapy. This long-term
      retrospective study is the first to compare radiologic and clinical data with
      patient assessments, to define more precise surgical indications. METHODS: All
      children presenting with hereditary multiple exostose during the period from 1990
      to 2010 were retrospectively analyzed. Masada forearm deformity classification,
      treatment, clinical course, and radiologic data were included from the
      preoperative period to the last follow-up. Operated mature patients self-assessed
      their functional handicap using the QuickDASH score. RESULTS: Eighteen children
      (27 forearms) were included. Thirteen of the children had forearm operations, one
      twice, on the average at 11.1 +/- 3 years of age. The average age at last follow
      up was 17.6 +/- 3.7 years. Data analysis showed no significant functional and
      radiologic improvement between the early postoperative period and last follow-up.
      Average QuickDASH score was 15.3 +/- 14.9 (out of 100), indicating minor self
      assessed handicap despite major clinical and radiologic abnormalities.
      CONCLUSIONS: Symptomatic radial head instability appears to be an indication for
      ulnar lengthening surgery. Even severe deformity without dislocation may be
      managed conservatively given the lack of postoperative functional improvement.
      Corrective radial osteotomy may be considered near the end of the growth spurt.
      LEVEL OF EVIDENCE: Level IV.

PMID- 23147630
TI  - Neuropsychiatric symptoms and problems among children with idiopathic toe
      walking.
AB  - BACKGROUND: Idiopathic toe-walking (ITW) is a condition in which otherwise
      healthy children walk on their toes. The diagnosis is a diagnosis of exclusion.
      The aim of this study was to elucidate the occurrence of neuropsychiatric
      symptoms among 5- to 13-year-old children with ITW. METHODS: Fifty-one
      consecutive children (31 boys, 20 girls) with a mean age of 9 years and 1 month
      were referred to a pediatric orthopaedic unit for ITW. Evaluations included
      assessments by a pediatric orthopaedic surgeon and a pediatric neurologist and
      the parents were asked to complete the Five to Fifteen questionnaire, a validated
      screening tool for neuropsychiatric problems. The study cohort was compared with
      an age-matched normative group previously described. RESULTS: In the study group,
      the percentage of children scoring above the 90th percentile, indicating
      difficulties, were for the different domains; motor skills 39.0%, executive
      functions 17.6%, perception 25.5%, memory 23.5%, language 23.5%, learning 25.9%,
      social skills 25.5%, and emotional/behavioural problems 21.6%. CONCLUSIONS:
      Children with ITW as a group displayed more neuropsychiatric problems than a
      normative group of age-matched children. These findings merit future larger
      studies. Furthermore, when children with ITW are referred for orthopaedic or
      neurological assessment, a structured neuropsychiatric history is advisable and
      further neuropsychiatric investigations should be considered. LEVEL OF EVIDENCE:
      II.

PMID- 23147629
TI  - Percutaneous curettage and suction for pediatric extremity aneurysmal bone cysts:
      is it adequate?
AB  - BACKGROUND: The purpose of our study was to evaluate the effectiveness of
      treating extremity aneurysmal bone cysts (ABC) by percutaneous curettage compared
      with open intralesional excision. METHODS: A retrospective review of 17 patients
      with histologically proven primary ABCs and no evidence of a secondary lesion
      treated either by percutaneous curettage or open intralesional excision with at
      least 24-month follow-up was undertaken. The percutaneous curettage group was
      uniformly treated on an outpatient basis using angled curettes under image
      guidance followed by intralesional evacuation. The primary outcome was
      radiographic healing using the Neer/Cole 4-grade classification. Complications
      were noted. RESULTS: Seventeen patients with a mean age of 11.7 years (range, 1.7
      to 17.5) were evaluated. Nine patients underwent percutaneous curettage and 8 had
      an open intralesional excision. The 2 treatment groups were comparable with
      regard to age, sex, number of procedures, morphologic type of ABC, and follow-up
      period. At follow-up, the proportion of patients with satisfactory healing
      (Neer/Cole grades I and II) were similar among the 2 groups (P = 0.74). In the
      percutaneous curettage group, 2 cases recurred necessitating repeat procedures,
      whereas 1 case recurred in the open intralesional excision group and was
      successfully treated percutaneously. CONCLUSIONS: Percutaneous curettage is a
      safe and minimally invasive alternative for extremity ABCs that can be performed
      as an outpatient procedure. Not all ABCs require wide exposure and an open
      intralesional excision. LEVEL OF EVIDENCE: III.

PMID- 23147631
TI  - A comparison of hip dislocation rates and hip containment procedures after
      selective dorsal rhizotomy versus intrathecal baclofen pump insertion in
      nonambulatory cerebral palsy patients.
AB  - BACKGROUND: Spasticity is the major etiology for hip dislocation in nonambulatory
      cerebral palsy patients. Selective dorsal rhizotomy (SDR) was used to control
      lower extremity spasticity, but is now done infrequently in nonambulatory
      cerebral palsy. Current surgical treatment is usually intrathecal baclofen pump
      (ITBP) placement. A major theoretical difference between SDR and ITBP is the
      effect on the iliopsoas through the L1 nerve root. This study compares the rate
      of hip dislocation and the need for further hip surgeries in SDR and ITBP
      patients. METHODS: All nonambulatory cerebral palsy patients who had either an
      SDR or ITBP and had minimum follow-up of 2 years were retrospectively reviewed
      for demographic data and timing, total number, and type of hip procedures (soft
      tissue vs. bony), and occurrence of hip dislocation. chi (2)test was used to
      assess for statistical significance. RESULTS: Sixty-nine patients who underwent
      SDR (40 males) and 50 patients who underwent ITBP (27 males) were included in the
      study. Average age at spasticity intervention was 6 years 11 months for SDR and 9
      years 8 months for ITBP. In the SDR group, 25% of hips underwent reconstruction
      versus 32% of hips in the ITBP group. There were a total of 19 hip procedures in
      the SDR group and 20 in the ITBP group (P = 0.15). Seventeen soft-tissue
      procedures were performed in both SDR and ITBP groups (P = 0.265). Six bony
      procedures (0 salvage) were performed in the SDR group and 10 in the ITBP group
      (4 salvage; P = 0.075). At final follow-up the hip dislocation rate was 10.6% in
      the SDR group and 7.4% in the ITBP group. CONCLUSIONS: There was no significant
      difference in the rate of secondary hip reconstructive surgery or dislocation
      between nonambulatory cerebral palsy patients who underwent SDR versus ITBP.
      Reconstruction was required for 25% to 32% of hips despite spasticity
      intervention with either procedure. This suggests that the L1 nerve root alone
      does not play a major role in the progression of hip dislocation. LEVEL OF
      EVIDENCE: Level 3--therapeutic study.

PMID- 23147632
TI  - Growth arrest of the capitellar physis after displaced lateral condyle fractures
      in children.
AB  - BACKGROUND: Fractures of the lateral humeral condyle represent the second most
      common elbow fracture in children and the most common physeal fracture about the
      elbow. Growth disturbances after this fracture, including premature physeal
      arrest, are rare but important complications. Only 4 radiographically documented
      reports of premature physeal arrest exist to date with just 1 offering
      comparative views. No computed tomography (CT) evidence of this event has
      previously been reported in the literature. The purpose of this study is to
      provide well-documented radiographic evidence of premature capitellar growth
      arrest, substantiated by CT imaging. METHODS: We reviewed the radiographic and
      clinical records of 3 patients (mean age, 6.9 y) that presented with Jakob type
      III fractures. All fractures were treated with open reduction and internal
      fixation. Follow-up ranged from 1.6 to 11.1 years (mean, 6.0 y). Radiographs were
      evaluated for any growth disturbances, including premature capitellar-metaphyseal
      fusion, lateral spur formation, changes in the humeral-ulnar angles, and fishtail
      deformities. Contralateral elbow radiographs were utilized for comparison when
      available. Clinical findings at last follow-up were provided for clinical
      correlation. RESULTS: The mean time to arrest and age at arrest were 2.6 and 9.5
      years, respectively. At last follow-up, patient 1 was functionally asymptomatic,
      showed a 6-degree increase in the humeral-ulnar angle, an increase in the
      carrying angle, and a fishtail deformity. Patient 2 was functionally
      asymptomatic, showed equal humeral-ulnar angles, and a small lateral spur
      formation on the injured side. Patient 3 was functionally symptomatic with pain
      and a 15-degree loss of extension on the injured side. There was also a 13-degree
      increase in the humeral-ulnar angle with an increase in carrying angle of
      approximately 8 degrees. CONCLUSIONS: This is the first study to radiographically
      document premature physeal arrest after lateral condyle fractures using both
      comparative views and CT imaging. It is important for surgeons to be aware of
      this potential complication after lateral condyle fractures of the humerus and to
      diligently monitor patients annually for possible intervention until they have
      achieved skeletal maturity. LEVEL OF EVIDENCE: Level IV--case series.

PMID- 23147633
TI  - Surgical technique for balancing posterior spinal fusions to the pelvis using the
      T square of Tolo.
AB  - BACKGROUND: Correcting pelvic obliquity and improving sitting balance in
      neuromuscular scoliosis often requires fixation to the pelvis. We describe the
      use of a T square instrument to assist intraoperatively in evaluating the
      alignment of these curves and achieving balance in the coronal plane. METHODS:
      The T square instrument was constructed with a vertical limb perpendicular to 2
      horizontal limbs in a T formation. At the conclusion of the instrumentation and
      preliminary reduction maneuvers, the T square was positioned with the horizontal
      limbs parallel to the pelvis and the vertical limb in line with the central
      sacral line. If the spine and pelvis were well balanced, fluoroscopic images
      demonstrated that the superior aspect of the vertical limb of the T square was
      crossing the vertebral body of T1. If this was not shown, then some combination
      of compression, distraction, or a change in the contouring of the rods was
      performed until this balance was achieved. RESULTS: In this series, we describe
      case examples in which the T square has been successfully used to aid in
      achieving balance in the coronal plane. This technique helps to overcome the
      challenges with positioning and imaging often encountered in managing these long,
      rigid curves. The T square is a useful adjunct in balancing posterior spinal
      fusions and evaluating the correction of pelvic obliquity in cases of
      neuromuscular scoliosis. CONCLUSIONS: This novel, yet simple, T square technique
      can be used for any method of posterior spinal fusion with lumbopelvic fixation
      to assist in the intraoperative evaluation and achievement of balance in the
      coronal plane and has become routine at our institution. LEVEL OF EVIDENCE: IV.

PMID- 23147634
TI  - Preoperative templating before spinal fusion using a fluoroscopic multiplanar
      imaging system is as accurate as CT scan and uses substantially less radiation.
AB  - BACKGROUND: Many surgeons utilize preoperative multiplanar imaging for surgical
      planning before fusion surgery using pedicle screw instrumentation. Computed
      tomographic (CT) scan is often used but limited by non-weight-bearing images and
      high-ionizing radiation. The purpose of this study was to compare pedicle length
      and width measurements using a multiplanar fluoroscopic imaging system and CT
      with gross measurements to validate the accuracy of multiplanar fluoroscopic
      imaging and compare relative radiation exposure between techniques. METHODS:
      Thirteen intact cadaveric lumbar spine segments were imaged using multiplanar
      fluoroscopic imaging and conventional CT scan using a low-dose pediatric
      protocol. At each level and each imaging modality, the 26 pedicles were measured
      digitally for width and pedicle screw length in accordance with typical
      presurgical planning procedures. All images were independently measured by 3
      observers. After measurement, the specimens were sectioned using a microsurgical
      saw to facilitate anatomic measurements using calipers. Measurements of the
      multiplanar fluoroscopic imaging and CT were compared with direct anatomic
      measurements to quantitate and compare measurement accuracy of CT and
      fluoroscopic imaging. At the time of image acquisition, radiation exposure from
      each modality was quantified to allow for comparison of radiation exposures.
      RESULTS: CT and multiplanar fluoroscopy had similar agreement with gross
      measurements with respect to pedicle width and length, with kappa values for
      comparison of CT and fluoroscopy with gross measurements falling between 0.61 and
      0.73. Both modalities underestimated pedicle width (by 1.9 mm for both
      modalities) and length (5.5 mm for CT, 6.6 mm for fluoroscopy). Interobserver
      reliability was higher for fluoroscopy versus CT. High-dose fluoroscopic imaging
      used 31% of the radiation exposure for CT. CONCLUSIONS: Multiplanar fluoroscopic
      imaging provides comparable diagnostic preoperative planning to CT scan in an
      experimental cadaveric model. The use of multiplanar fluoroscopic imaging
      resulted in between 69% and 85% less radiation exposure than conventional CT scan
      using pediatric settings. CLINICAL EVIDENCE: This study demonstrates similar
      results from simulated preoperative templating using fluoroscopic imaging
      compared with CT scan but with less radiation exposure.

PMID- 23147635
TI  - Validation of a scoliometer smartphone app to assess scoliosis.
AB  - BACKGROUND: Surgeons and software developers recognize that apps can improve
      patient care by replicating the function of existing medical devices. However,
      the incorporation of new tools requires that the clinical data being recorded is
      accurate and valid. This study attempts to validate a new iPhone app to measure
      scoliotic rotation. The objective of this study was to validate the scoliogauge
      iPhone application by comparing the results to simultaneous readings from a
      standard Scoliometer. METHODS: Four orthopaedic medical providers (attending
      surgeon, fellow, resident, and nurse practitioner) each read a standard
      scoliometer at 60 randomly selected angular measurements between -30 and 30
      degrees, whereas a blinded observer simultaneously recorded the angular
      measurement derived from the scoligauge app. The correlation between the 2
      measurements were calculated using a Pearson correlation coefficient with a P
      value set to < 0.05 for significance. RESULTS: The Pearson correlation values
      ranged from 0.9994 to 0.9996 for all providers and all P-values < 0.001. There
      was no increase in time associated with using the app compared with the standard
      device. CONCLUSIONS: The scoligauge app is a convenient novel tool that
      replicates the function of a standard clinical scoliometer but with a potentially
      decreased financial cost and greater convenience for providers. CLINICAL
      RELEVANCE: Validation of this new device demonstrates the potential to increase
      the distribution of cost-effective scoliosis screening tools to a broad
      population of medical providers.

PMID- 23147636
TI  - Giant cell tumor of a lumbar vertebra in a 7-year-old child:  a case report.
AB  - STUDY DESIGN: This case provides a rare occurrence of a giant cell tumor (GCT) in
      posterior elements of a lumbar vertebra in a 7-year-old child with successful
      outcome after surgical excision and regular follow-ups. OBJECTIVE: To present a
      unique case report of a pediatric GCT in the vertebral column and results.
      SUMMARY OF BACKGROUND DATA: GCT is a rare bone tumor seen in 3% to 5% of primary
      bone neoplasm. Approximately 7% of GCTs are found in the vertebral column. GCT of
      the spine is found in only 5% to 7% of cases and can occur in any region of the
      spine but are believed to be predominantly in the sacrum. Despite its benign
      nature, expansion in a confined space makes early detection of spinal GCTs
      important to prevent occurrence of compressive myelopathy/radiculopathy. The
      presence of a GCT in a child younger than 10 years of age, in posterior elements
      of a lumbar vertebral body, has not been reported earlier. METHODS: On the basis
      of the clinical history, radiograph of the thoracolumbar spine, computed
      tomography of lumbar spine, and magnetic resonance imaging, a preliminary
      diagnosis of osteoblastoma was made. RESULTS: The patient presented with a lytic
      lesion with involvement of posterior elements, 1 side the pedicle extending into
      the body of a lumbar vertebra (L3) and had extension into the paraspinal muscles.
      Intraoperative exploration and frozen section showed the presence of a typical
      histologic picture of a GCT. Ipsilateral pedicle, posterior elements, and the
      superior articular facet were excised. En bloc resection was found not to be
      feasible due to the friable nature of the tumor and involvement of the soft
      tissues. In addition, fusion was avoided with consideration of the young age of
      the patient. CONCLUSIONS: The patient has been free of any recurrence as of his
      last follow-up visit.

PMID- 23147637
TI  - The use of bone grafts and bone graft substitutes in pediatric orthopaedics:  a
      molecular mechanism.

PMID- 23147638
TI  - Spinal transection induces widespread proliferation of cells along the length of
      the spinal cord in a weakly electric fish.
AB  - The ability to regenerate spinal cord tissue after tail amputation has been well
      studied in several species of teleost fish. The present study examined the
      proliferation and survival of cells following complete spinal cord transection
      rather than tail amputation in the weakly electric fish Apteronotus
      leptorhynchus. To quantify cell proliferation along the length of the spinal
      cord, fish were given a single bromodeoxyuridine (BrdU) injection immediately
      after spinal transection or sham surgery. Spinal transection significantly
      increased the density of BrdU+ cells along the entire length of the spinal cord
      at 1 day posttransection (dpt), and most newly generated cells survived up to 14
      dpt. To examine longer-term survival of the newly proliferated cells, BrdU was
      injected for 5 days after the surgery, and fish were sacrificed at 14 or 30 dpt.
      Spinal transection significantly increased cell proliferation and/or survival, as
      indicated by an elevated density of BrdU+ cells in the spinal cords of spinally
      transected compared to sham-operated and intact fish. At 14 dpt, BrdU+ cells were
      abundant at all levels of the spinal cord. By 30 dpt, the density of BrdU+ cells
      had decreased at all levels of the spinal cord except at the tip of the tail.
      Thus, newly generated cells in the caudal-most segment of the spinal cord
      survived longer than those in more rostral segments. Our findings indicate that
      spinal cord transection stimulates widespread cellular proliferation; however,
      there were regional differences in the survival of the newly generated cells.

PMID- 23147639
TI  - Anti-proliferative effect of (19Z)-halichondramide, a novel marine macrolide
      isolated from the sponge Chondrosia corticata, is associated with G2/M cell cycle
      arrest and suppression of mTOR signaling in human lung cancer cells.
AB  - Five oxazole-containing macrolides isolated from the marine sponge Chondrosia
      corticata were evaluated for their anti-proliferative activity in a panel of
      human solid cancer cell lines. (19Z)-Halichondramide ((19Z)-HCA), a novel
      trisoxazole-containing macrolide, exhibited the highest potency among the
      macrolides, with IC50 values in the submicro-molar ranges. Prompted by the high
      potency of growth inhibition of cancer cells, we investigated the mechanism of
      action of the anti-proliferative activity of (19Z)-HCA in human A549 lung cancer
      cells. (19Z)-HCA induced cell cycle arrest in the G2/M phase, and this event was
      highly correlated with the expression of checkpoint proteins, including the up
      regulation of p53 and GADD45alpha and the down-regulation of cyclin B1, cyclin A,
      CDC2, and CDC25C. In addition, the growth inhibition by (19Z)-HCA was associated
      with the suppression of mTOR and its downstream effector molecules 4EBP1 and
      p70S6K. The modulation of mTOR signaling by (19Z)-HCA was found to be mediated by
      the regulation of upstream proteins, including the down-regulation of Akt and p38
      MAPK and the up-regulation of AMPK. These data suggest the potential of (19Z)-HCA
      to serve as a candidate for cancer chemotherapeutic agents derived from marine
      organisms by virtue of arresting the cell cycle in the G2/M phase and the
      modulation of mTOR/AMPK signaling pathways.

PMID- 23147640
TI  - A high-throughput dual parameter assay for assessing drug-induced mitochondrial
      dysfunction provides additional predictivity over two established mitochondrial
      toxicity assays.
AB  - Mitochondrial toxicity is a major reason for safety-related compound attrition
      and post-market drug withdrawals, highlighting the necessity for higher
      throughput screens that can identify this mechanism of toxicity during the early
      stages of drug discovery. Here, we present the validation of a 384-well dual
      parameter plate-based assay capable of measuring oxygen consumption and
      extracellular acidification in intact cells simultaneously. The assay showed good
      reproducibility and robustness and is suitable for use with both suspension cells
      and adherent cells. To determine if the assay provides additional value in
      detecting mitochondrial toxicity over existing platforms, 200 commercially
      available drugs were tested in the assay using HL60 suspension cells as well as
      in two conventional mitochondrial toxicity assays: an oxygen consumption assay
      that uses isolated mitochondria and a cell-based assay that uses HepG2 cells
      grown in glucose and galactose media. The combination of the dual parameter assay
      and the isolated mitochondrial oxygen consumption assay identified more compounds
      that caused mitochondrial impairment than any other combination of the three
      assays or each of the three assays on its own. Furthermore, novel information was
      obtained from the dual parameter assay on drugs not previously reported to cause
      mitochondrial impairment.

PMID- 23147641
TI  - Carboplatin resistant human laryngeal carcinoma cells are cross resistant to
      curcumin due to reduced curcumin accumulation.
AB  - Curcumin is a natural compound that exhibits a wide range of beneficial effects,
      among them the anti-tumor activity. Recently it was shown that curcumin may be
      efficient against drug resistant tumor cells. The goal of our investigation was
      to examine if human laryngeal carcinoma cells resistant to carboplatin display
      sensitivity to curcumin, as compared to parental cells, and if this sensitivity
      is altered, to determine the molecular mechanisms that are responsible for it. We
      found that carboplatin resistant 7T cells were also cross resistant to curcumin.
      After the treatment with equimolar concentration of curcumin, 7T cells exhibited
      lower intracellular accumulation of curcumin which coincided with reduced
      formation of reactive oxygen species (ROS), diminished lipid and DNA damage
      followed by reduced induction of apoptosis and expression of heat shock protein
      70 (Hsp70), as compared to parental HEp-2 cells. However, after the treatment
      with equitoxic concentration of curcumin, intracellular accumulation and all the
      explored downstream effects were similar in both cell lines suggesting that
      resistance of 7T cells to curcumin was based on its reduced intracellular
      accumulation. Since curcumin accumulates mostly in the membranes, we explored the
      fatty acid composition of both cell lines, but we did not find any difference
      between them.

PMID- 23147642
TI  - Bioimpedance spectroscopy as a measure of physical functioning in nursing home
      residents.
AB  - BACKGROUND AND AIMS: Intracellular resistance (Ri), a raw measure of bioimpedance
      spectroscopy (BIS), has been suggested for assessment of muscle health. The
      associations of repeated BIS measurements with functioning and nutritional status
      were investigated in nursing home residents suffering from poor health and
      disabilities. METHODS: A total of 106 nursing home residents (age 83+/-8 yrs, 75%
      women) were recruited. Whole body and calf BIS measures (lean body mass,
      resistance at 50 kHz, and Ri), height and calf electrode distance (D) were used
      to calculate six muscle indices. Hand grip and knee extension strengths were
      measured and data on Activities of Daily Living (ADL), mobility score, and Mini
      Nutritional Assessment (MNA) collected. Repeated measurements were performed at 3
      (BIS) and 6 months (BIS, muscle strength, ADL, mobility, and MNA). RESULTS: All
      bioimpedance muscle indices were lower in women than men and associated with MNA.
      However, the calf skeletal muscle index (SMI=D2/Ri) associated with muscle
      strength measurements at baseline and consistently with mobility and ADL also at
      6-month re-examination. When compared to the highest tertile of SMI percent
      change (cut point +0.7%), the patients in the lowest tertile (cut point - 11.6%)
      had a 5.3-fold risk (p=0.004) for mobility decline within the 6-month follow-up.
      This risk association also remained significant after controlling for age,
      gender, baseline mobility, and percent change in body weight. CONCLUSIONS: Calf
      intracellular resistance related to electrode distance is associated with the
      activities of daily living reflecting mobility in typical nursing home residents
      and a decrease in this index indicates a markedly increased risk for mobility
      decline.

PMID- 23147643
TI  - Quantitative integral cross sections for the H + CO2 -> OH + CO reaction from a
      density functional theory-based potential energy surface.
AB  - The OH + CO -> H + CO(2) reaction is important in combustion, atmospheric, and
      interstellar chemistry. Whereas the direct reaction has been extensively studied
      both experimentally and theoretically, the reverse reaction has received
      relatively less attention. Here we carry out a quasiclassical trajectory study of
      the hyperthermal H + CO(2)-> OH + CO reaction on a new interpolated potential
      energy surface based on the M06-2X density functional. The results reveal for the
      first time quantitative agreement with experiment for the reaction cross sections
      in the range of relative translational energies 1.2-2.5 eV. We attribute this
      excellent agreement to both the quality of the M06-2X energies, which closely
      reproduce CCSD(T) energies, and to the potential surface construction strategy
      that emphasizes both the direct and reverse reactions.

PMID- 23147644
TI  - Signal transduction for Schistocerca gregaria ion transport peptide is mediated
      via both cyclic AMP and cyclic GMP.
AB  - The second messengers involved in the signal transduction for Schistocerca
      gregaria, ion transport peptide (Schgr-ITP) that regulates ion and fluid
      transport across the ileum of the desert locust S. gregaria, were measured using
      competitive enzyme-linked immunosorbent assays (ELISAs). Synthetic Schgr-ITP
      elevates intracellular levels of both cyclic AMP and cyclic GMP, measured over a
      15 min period in the presence of 3-isobutyl-1-methylxanthine, in a dose-dependent
      manner. Furthermore, crude corpora cardiaca (CC) extracts elevate intracellular
      cyclic AMP levels 2-fold greater than Schgr-ITP, suggesting that factors present
      in the CC, other than Schgr-ITP, also act via this second messenger. These
      results suggest that the interaction of Schgr-ITP with two separate receptors,
      most likely a G-protein coupled receptor and a membrane bound guanylate cyclase,
      elevates intracellular levels of cyclic AMP and cyclic GMP to regulate ion and
      fluid transport across the locust ileum. Cyclic AMP stimulates Cl(-), K(+) and
      Na(+) reabsorption, whereas secretion of H(+) into the lumen of the ileum is most
      likely mediated via cyclic GMP. Cyclic GMP also stimulates Cl(-) uptake in a
      similar manner to cyclic AMP. The measurement of tissue (central nervous system)
      levels of Schgr-ITP using an indirect ELISA confirms that the peptide is only
      present in the locust brain and the CC. The amounts present are greatest in the
      CC, where the peptide is presumably stored for release into the hemolymph when
      locusts feed.

PMID- 23147646
TI  - Metal concentrations, growth and condition indices in European juvenile flounder
      (Platichthys flesus) relative to sediment contamination levels in four Eastern
      English Channel estuaries.
AB  - The aim of the present study was to evaluate the effects of metal contamination
      on the biological responses of 0-group juvenile European flounder and to assess
      and compare the quality of four estuarine habitats located in the Eastern English
      Channel. Fish otolith growth and condition indices (RNA : DNA ratio, Fulton's K
      condition index) were measured and found to be significantly lower in individuals
      from the Seine estuary compared to those of the Canche, Authie and Somme
      estuaries. No obvious effects of hydrological condition or food availability on
      the flounder biological responses were observed. Sediments from the Seine showed
      the highest metal concentrations, bioavailable proportion and enrichment factors.
      Higher metal concentrations were observed in fish from the Seine compared to the
      other ones caught in less polluted estuaries. These results suggest that
      contaminants may have a negative impact on the early life history stage of
      flounder.

PMID- 23147645
TI  - Effect of the disintegrin eristostatin on melanoma-natural killer cell
      interactions.
AB  - Malignant melanoma is difficult to treat due to its resistance to
      chemotherapeutic regimens. Discovery of new pharmaceuticals with inhibitory
      potential can be helpful in the development of novel treatments. The snake venom
      disintegrin eristostatin, from the viper Eristicophis macmahoni, caused
      immunodeficient mice to be significantly protected from development of lung
      colonization when melanoma cells and the disintegrin were co-injected in vivo
      into the lateral tail vein compared to vehicle controls. Cytotoxicity assays
      suggested that eristostatin makes the melanoma cells a better target for lysis by
      human natural killer cells. Direct binding assays using atomic force microscopy
      showed eristostatin does specifically bind the surface of the six melanoma cell
      lines tested. Eristostatin binding was partially inhibited by the addition of
      soluble RGDS peptide, suggesting an integrin as one likely, but not the sole,
      binding partner. Studies done with melanoma cells on a culture dish and natural
      killer cells attached to a cantilever tip in atomic force microscopy showed four
      major populations of interactions which exhibited altered frequency and unbinding
      strength in the presence of eristostatin.

PMID- 23147647
TI  - Base-pairing selectivity of a ureido-linked phenyl-2'-deoxycytidine derivative.
AB  - Incorporation of modified nucleotides into nucleic acid strands often produces
      conformational constraints and steric hindrances that may change the property of
      base pairing. In this study, we investigated a 2'-deoxycytidine derivative that
      tethers a phenyl moiety to the exocyclic amino group of cytosine linked through a
      ureido group. This derivative compound is structurally similar to the
      carbamoylated DNA base lesions produced in cells. The thermodynamic and
      structural studies showed that the modified dC formed the base pair with dG in
      the complementary strand, but the base-pairing selectivity toward dG was
      decreased under poly(ethylene glycol)-mediated osmotic stress. The phenyl group
      and the ureido linker attached to dC provided selectivity for the formation of
      base pairing exclusively with dG in a wide range of pH conditions, whereas
      unmodified dC stabilized the pairings with dA or dC in acidic solutions.
      Moreover, this modified base could not form self-pairing through intermolecular
      hydrogen bonds. We suggest that formation of weak pairing and protonation of the
      cytosine base are hindered due to the base modification. These data provide
      insights into the pairing selectivity of carbamoylated cytosine lesions produced
      in cells, and suggest applications of the 2'-deoxycytidine derivatives in medical
      technologies, molecular biology experiments, and synthesis of a supramolecular
      network of DNA strands.

PMID- 23147648
TI  - Normal hearing after trauma with completely ectopic incus -- how possible?.
AB  - OBJECTIVES: To report the rare case of a patient with complete incus dislocation
      after trauma showing normal hearing. METHODOLOGY: Physical examination,
      audiometry, CT of temporal bone, and detection during operation. RESULTS: The
      incus had become remotely located in the mastoid cavity, but the patient showed
      normal hearing because fibrous connections had preserved bony continuity.
      CONCLUSION: This case demonstrates that disruption of the ossicular chain does
      not always require ossicular reconstruction.

PMID- 23147649
TI  - Structure and spectroscopy of a bidentate bis-homocitrate dioxo-molybdenum(VI)
      complex: insights relevant to the structure and properties of the FeMo-cofactor
      in nitrogenase.
AB  - Direct reaction of potassium molybdate (with natural abundance Mo or enriched
      with (92)Mo or (100)Mo) with excess hydrolyzed homocitric acid-gamma-lactone in
      acidic solution resulted in the isolation of a cis-dioxo bis-homocitrato
      molybdenum(VI) complex, K(2)[*MoO(2)(R,S-H(2)homocit)(2)].2H(2)O (1) (*Mo=Mo, 1;
      (92)Mo, 2; (100)Mo, 3; H(4)homocit=homocitric acid-gamma-lactone.H(2)O) and
      K(2)[MoO(2)((18)O-R,S-H(2)homocit)(2)].2H(2)O (4). The complex has been
      characterized by elemental analysis, FT-IR, solid and solution (13)C NMR, and
      single crystal x-ray diffraction analysis. The molybdenum atom in (1) is quasi
      octahedrally coordinated by two cis oxo groups and two bidentate homocitrate
      ligands. The latter coordinates via its alpha-alkoxy and alpha-carboxy groups,
      while the beta- and gamma-carboxylic acid groups remain uncomplexed, similar to
      the coordination mode of homocitrate in the Mo-cofactor of nitrogenase. In the IR
      spectra, the MoO stretching modes near 900 cm(-1) show 2-3 cm(-1) red- and blue
      shifts for the (92)Mo-complex (2) and (100)Mo-complex (3) respectively compared
      with the natural abundance version (1). At lower frequencies, bands at 553 and
      540 cm(-1) are assigned to nu(Mo-O) vibrations involving the alkoxide ligand. At
      higher frequencies, bands in the 1700-1730 cm(-1) region are assigned to
      stretching modes of protonated carboxylates. In addition, a band at 1675 cm(-1)
      was observed that may be analogous to a band seen at 1677 cm(-1) in nitrogenase
      photolysis studies. The solution behavior of (1) in D(2)O was probed with (1)H
      and (13)C NMR spectra. An obvious dissociation of homocitrate was found, even
      though bound to the high valent Mo(VI). This suggests the likely lability of
      coordinated homocitrate in the FeMo-cofactor with its lower valence Mo(IV).

PMID- 23147651
TI  - A method for deriving water-quality benchmarks using field data.
AB  - The authors describe a methodology that characterizes effects to individual
      genera observed in the field and estimate the concentration at which 5% of genera
      are adversely affected. Ionic strength, measured as specific conductance, is used
      to illustrate the methodology. Assuming some resilience in the population, 95% of
      the genera are afforded protection. The authors selected an unambiguous effect,
      the presence or absence of a genus from sampling locations. The absence of a
      genus, extirpation, is operationally defined as the point above which only 5% of
      the observations of a genus occurs. The concentrations that cause extirpation of
      each genus are rank-ordered from least to greatest, and the benchmark is
      estimated at the 5th percentile of the distribution using two-point
      interpolation. When a full range of exposures and many taxa are included in the
      model of taxonomic sensitivity, the model broadly characterizes how species in
      general respond to a concentration gradient of the causal agent. This recognized
      U.S. Environmental Protection Agency methodology has many advantages.
      Observations from field studies include the full range of conditions, effects,
      species, and interactions that occur in the environment and can be used to model
      some causal relationships that laboratory studies cannot.

PMID- 23147650
TI  - Mesenchymal stem cells can improve anal pressures after anal sphincter injury.
AB  - OBJECTIVE: Fecal incontinence reduces the quality of life of many women but has
      no long-term cure. Research on mesenchymal stem cell (MSC)-based therapies has
      shown promising results. The primary aim of this study was to evaluate functional
      recovery after treatment with MSCs in two animal models of anal sphincter injury.
      METHODS: Seventy virgin female rats received a sphincterotomy (SP) to model
      episiotomy, a pudendal nerve crush (PNC) to model the nerve injuries of
      childbirth, a sham SP, or a sham PNC. Anal sphincter pressures and
      electromyography (EMG) were recorded after injury but before treatment and 10
      days after injury. Twenty-four hours after injury, each animal received either
      0.2 ml saline or 2 million MSCs labelled with green fluorescing protein (GFP)
      suspended in 0.2 ml saline, either intravenously (IV) into the tail vein or
      intramuscularly (IM) into the anal sphincter. RESULTS: MSCs delivered IV after SP
      resulted in a significant increase in resting anal sphincter pressure and peak
      pressure, as well as anal sphincter EMG amplitude and frequency 10 days after
      injury. MSCs delivered IM after SP resulted in a significant increase in resting
      anal sphincter pressure and anal sphincter EMG frequency but not amplitude. There
      was no improvement in anal sphincter pressure or EMG with in animals receiving
      MSCs after PNC. GFP-labelled cells were not found near the external anal
      sphincter in MSC-treated animals after SP. CONCLUSION: MSC treatment resulted in
      significant improvement in anal pressures after SP but not after PNC, suggesting
      that MSCs could be utilized to facilitate recovery after anal sphincter injury.

PMID- 23147652
TI  - Gene polymorphisms of interleukin-17 and interleukin-17 receptor are associated
      with end-stage kidney disease.
AB  - BACKGROUND: Inflammation could be a causal factor in progression of chronic
      kidney disease. To date, there is convincing experimental and clinical evidence
      to support the notion that interleukin (IL)-17-producing T cells contribute to
      kidney injury in renal diseases. However, the genetic relationship between end
      stage renal disease (ESRD) and the T-helper 17 pathway has never been studied. In
      this study, we hypothesized that polymorphisms of IL-17 or their receptors may be
      associated with ESRD. METHODS: A total of 290 nondiabetic ESRD patients and 289
      normal controls were included. We analyzed 13 single nucleotide polymorphisms
      located within the four genes of IL17A, IL17E, IL17RA and IL17RB. RESULTS: The
      ESRD patients had a significantly higher allele frequency compared to control
      subjects for the IL17E rs10137082*C and IL17RA rs4819554*A alleles. Genotyping
      analysis demonstrated that 2 SNPs among 13 were significantly associated with
      ESRD after adjusting for age and sex, which were shown by IL17E rs10137082 (odds
      ratio (OR) 1.48 in codominant 1, OR 1.54 in dominant, OR 1.47 in log-additive)
      and IL17RA rs4819554 (OR 1.46 in codominant 1, OR 1.79 in codominant 2, OR 1.54
      in dominant, OR 1.39 in log-additive). CONCLUSIONS: Two polymorphisms within the
      IL17E and IL17RA genes are associated with ESRD independent of age and sex. This
      is the first finding to suggest that genetic variations of IL17 genes affect the
      risk of development of ESRD.

PMID- 23147653
TI  - Divorce and women's risk of health insurance loss.
AB  - This article bridges the literatures on the economic consequences of divorce for
      women with that on marital transitions and health by focusing on women's health
      insurance. Using a monthly calendar of marital status and health insurance
      coverage from 1,442 women in the Survey of Income and Program Participation, we
      examine how women's health insurance changes after divorce. Our estimates suggest
      that roughly 115,000 American women lose private health insurance annually in the
      months following divorce and that roughly 65,000 of these women become uninsured.
      The loss of insurance coverage we observe is not just a short-term disruption.
      Women's rates of insurance coverage remain depressed for more than two years
      after divorce. Insurance loss may compound the economic losses women experience
      after divorce and contribute to as well as compound previously documented health
      declines following divorce.

PMID- 23147655
TI  - Microbiota: Gut microbiota produce alcohol in patients with NASH.

PMID- 23147656
TI  - Management of psoriatic lesions associated with anti-TNF therapy in patients with
      IBD.

PMID- 23147657
TI  - Diagnosis: Novel prognostic biomarkers in hepatocellular carcinoma.

PMID- 23147658
TI  - New treatments for IBS.
AB  - IBS is a common disorder that affects approximately 5-20% of the populations of
      Western countries; the main symptoms are abdominal pain and erratic, altered
      bowel habits, often accompanied by bloating. Despite an array of available
      pharmacological and nonpharmacological treatments aimed at a wide variety of
      gastrointestinal and brain targets, many patients do not report adequate symptom
      relief. The effect of IBS on an individual can be enormous, and the societal and
      financial costs overall are high, which is indicative of an unmet need for
      effective IBS treatments. Intense research efforts are ongoing that range from
      the development of new molecules for pharmacological therapies to testing the
      utility of internet technology to facilitate widespread delivery of efficacious
      behavioural therapy. This Review discusses the latest treatments for IBS,
      including novel nonpharmacological and pharmacological approaches. We have
      included estimates of the number needed to treat and the number needed to harm
      for selected treatments. Emerging and potential future treatments are included,
      with the data supporting an optimistic view about the future of IBS therapeutics.
      The ability to optimize therapy by individualizing management whilst also
      avoiding harm remains the key to achieving the best possible outcomes with
      currently available therapeutics.

PMID- 23147660
TI  - IBD: the IBD genome--new study findings contribute to an ever-growing gene
      catalogue.

PMID- 23147661
TI  - Imaging: a novel technique for imaging enteric ganglia.

PMID- 23147663
TI  - Pancreatic cancer: New genetic insights into pancreatic cancer.

PMID- 23147666
TI  - Viral hepatitis: a rare dendritic cell population produces IFN-lambda in HCV
      infection.

PMID- 23147664
TI  - Medical therapies for hepatocellular carcinoma: a critical view of the evidence.
AB  - The management of hepatocellular carcinoma (HCC) has substantially changed in the
      past few decades. Improvements in patient stratification (for example, using the
      Barcelona Clinic Liver Cancer staging system) and the introduction of novel
      therapies (such as sorafenib) have improved patient survival. Nevertheless, HCC
      remains the third most common cause of cancer-related deaths worldwide. Decision
      making largely relies on evidence-based criteria, as depicted in the US and
      European clinical practice guidelines, which endorse five therapeutic
      recommendations: resection; transplantation; radiofrequency ablation;
      chemoembolization; and sorafenib. However, areas still exist in which uncertainty
      precludes a strong recommendation, such as the role of adjuvant therapies after
      resection, radioembolization with yttrium-90 or second-line therapies for
      advanced HCC. Many clinical trials that are currently ongoing aim to answer these
      questions. The first reported studies, however, failed to identify novel
      therapeutic alternatives (that is, sunitinib, erlotinib or brivanib). Moreover,
      genomic profiling has enabled patient classification on the basis of molecular
      parameters, and has facilitated the development of new effective drugs. However,
      no oncogene addiction loops have been identified so far, as has been the case
      with other cancers such as melanoma, lung or breast cancer. Efforts that focus on
      the implementation of personalized medicine approaches in HCC will probably
      dominate research in the next decade.

PMID- 23147667
TI  - IBD: Ustekinumab shows promise in the treatment of refractory Crohn's disease.

PMID- 23147668
TI  - Biological network inference for drug discovery.
AB  - A better understanding of the pathophysiology should help deliver drugs whose
      targets are involved in the causative processes underlying a disease. Biological
      network inference uses computational methods for deducing from high-throughput
      experimental data, the topology and the causal structure of the interactions
      among the drugs and their targets. Therefore, biological network inference can
      support and contribute to the experimental identification of both gene and
      protein networks causing a disease as well as the biochemical networks of drugs
      metabolism and mechanisms of action. The resulting high-level networks serve as a
      foundational basis for more detailed mechanistic models and are increasingly used
      in drug discovery by pharmaceutical and biotechnology companies. We review and
      compare recent computational technologies for network inference applied to drug
      discovery.

PMID- 23147670
TI  - Current world literature.

PMID- 23147669
TI  - Blended learning in anesthesia education:  current state and future model.
AB  - PURPOSE OF REVIEW: Educators in anesthesia residency programs across the country
      are facing a number of challenges as they attempt to integrate blended learning
      techniques in their curriculum. Compared with the rest of higher education, which
      has made advances to varying degrees in the adoption of online learning
      anesthesiology education has been sporadic in the active integration of blended
      learning. The purpose of this review is to discuss the challenges in
      anesthesiology education and relevance of the Universal Design for Learning
      framework in addressing them. RECENT FINDINGS: There is a wide chasm between
      student demand for online education and the availability of trained faculty to
      teach. The design of the learning interface is important and will significantly
      affect the learning experience for the student. SUMMARY: This review examines
      recent literature pertaining to this field, both in the realm of higher education
      in general and medical education in particular, and proposes the application of a
      comprehensive learning model that is new to anesthesiology education and relevant
      to its goals of promoting self-directed learning.

PMID- 23147672
TI  - Gonadotropin-releasing hormone analogues reduce the proliferation of endometrial
      stromal cells but not endometriotic cells.
AB  - AIMS: We investigated the potential of gonadotropin-releasing hormone (GnRH)
      agonists and GnRH antagonists to inhibit cell proliferation in endometriotic and
      endometrial stromal cells. METHODS: Twenty patients with ovarian endometriomas
      and 18 patients with uterine fibromas were recruited. Endometriotic and
      endometrial stromal cells were obtained from the ovarian chocolate cyst linings
      and the eutopic endometria of premenopausal women with uterine fibromas,
      respectively. RESULTS: GnRH agonist or antagonist treatment attenuated tumor
      necrosis factor (TNF)-alpha-induced cell proliferation in the endometrial stromal
      cells, whereas endometriotic stromal cells did not respond to treatment. The
      endometriotic stromal cells exhibited a decreased expression of the type I GnRH
      receptor compared with the endometrial stromal cells. GnRH agonists or
      antagonists did not repress TNF-alpha-induced IL-8 production in endometriotic
      stromal cells. CONCLUSION: GnRH agonists and antagonists have similar effects in
      slowing the growth of endometrial stromal cells. Endometriotic stromal cells
      resist the antiproliferative effect of GnRH agonists and antagonists.

PMID- 23147673
TI  - Quality measurements in pediatrics: what do they assess?

PMID- 23147674
TI  - Transcript profiling of microRNAs during the early development of the maize brace
      root via Solexa sequencing.
AB  - To characterize the microRNAs that contribute to the development of brace root,
      Solexa high-throughput sequencing of three libraries derived from tissues of node
      (N), nodes with just-emerged brace roots (NR), and nodes with just-emerged brace
      roots after IAA treatment (NRI) was performed. Total 650,793, 957,303 and
      1,082,948 genome-matched unique reads were obtained in N, NR and NRI libraries,
      respectively. Further analysis confirmed the authenticity of 137 known miRNAs and
      the discovery of 159 novel miRNAs in maize. 14 conserved and 16 novel miRNAs
      differentially expressed in brace root, as well as 15 target genes, were
      identified and validated by qRT-PCR during maize brace root development.
      Moreover, we identified 9 miRNA precursor-matched novel sRNAs that may form miRNA
      clusters, as well as 24 nt siRNAs in the three libraries. In addition, we suggest
      that auxin represent a regulator in brace root development and can be regulated
      at the posttranscriptional level by miRNAs.

PMID- 23147675
TI  - Gene-based copy number variation study reveals a microdeletion at 12q24 that
      influences height in the Korean population.
AB  - Height is a classic polygenic trait with high heritability (h(2)=0.8). Recent
      genome-wide association studies have revealed many independent loci associated
      with human height. In addition, although many studies have reported an
      association between copy number variation (CNV) and complex diseases, few have
      explored the relationship between CNV and height. Recent studies reported that
      single nucleotide polymorphisms (SNPs) are highly correlated with common CNVs,
      suggesting that it is warranted to survey CNVs to identify additional genetic
      factors affecting heritable traits such as height. This study tested the
      hypothesis that there would be CNV regions (CNVRs) associated with height nearby
      genes from the GWASs known to affect height. We identified regions containing >1%
      copy number deletion frequency from 3667 population-based cohort samples using
      the Illumina HumanOmni1-Quad BeadChip. Among the identified CNVRs, we selected 15
      candidate regions that were located within 1Mb of 283 previously reported genes.
      To assess the effect of these CNVRs on height, statistical analyses were
      conducted with samples from a case group of 370 taller (upper 10%) individuals
      and a control group of 1828 individuals (lower 50%). We found that a newly
      identified 17.7 kb deletion at chromosomal position 12q24.33, approximately 171.6
      kb downstream of GPR133, significantly correlated with height; this finding was
      validated using quantitative PCR. These results suggest that CNVs are potentially
      important in determining height and may contribute to height variation in human
      populations.

PMID- 23147676
TI  - Functional insights into the core-TFIIH from a comparative survey.
AB  - TFIIH is a eukaryotic complex composed of two subcomplexes, the CAK (Cdk
      activating kinase) and the core-TFIIH. The core-TFIIH, composed of seven subunits
      (XPB, XPD, P62, P52, P44, P34, and P8), plays a crucial role in transcription and
      repair. Here, we performed an extended sequence analysis to establish the
      accurate phylogenetic distribution of the core-TFIIH in 63 eukaryotic organisms.
      In spite of the high conservation of the seven subunits at the sequence and
      genomic levels, the non-enzymatic P8, P34, P52 and P62 are absent from one or a
      few unicellular species. To gain insight into their respective roles, we
      undertook a comparative genomic analysis of the whole proteome to identify the
      gene sets sharing similar presence/absence patterns. While little information was
      inferred for P8 and P62, our studies confirm the known role of P52 in repair and
      suggest for the first time the implication of the core TFIIH in mRNA splicing via
      P34.

PMID- 23147677
TI  - Database tools in genetic diseases research.
AB  - The knowledge of the human genome is in continuous progression: a large number of
      databases have been developed to make meaningful connections among worldwide
      scientific discoveries. This paper reviews bioinformatics resources and database
      tools specialized in disseminating information regarding genetic disorders. The
      databases described are useful for managing sample sequences, gene expression and
      post-transcriptional regulation. In relation to data sets available from genome
      wide association studies, we describe databases that could be the starting point
      for developing studies in the field of complex diseases, particularly those in
      which the causal genes are difficult to identify. 

PMID- 23147680
TI  - Spontaneous electric fields in films of CF3Cl, CF2Cl2 and CFCl3.
AB  - Data are presented showing the spontaneous formation of electric fields within
      solid films of the chlorofluorocarbons (CFCs) CF(3)Cl, CF(2)Cl(2) and CFCl(3) as
      a function of film deposition temperature from 40 K and above. Electric fields,
      which arise through dipole alignment and lie in the range of a few times 10(7) V
      m(-1) to a few times 10(6) V m(-1), decrease as the degree of chlorination
      increases. Maximum deposition temperatures for display of an electric field lie
      at ~50 K, ~65 K and ~52 K for CF(3)Cl, CF(2)Cl(2) and CFCl(3) respectively.
      CFCl(3) films possess electric fields which show an onset of temporal
      metastability between deposition temperatures of 46 K and 50 K. CF(3)Cl and
      CF(2)Cl(2) demonstrate temperatures of ~65 K and ~80 K at which the electric
      field in the film is removed by heating, so-called Curie points, with decay of
      the field spread over more than 10 K. CFCl(3) displays a comparatively sharp
      Curie point at 55 K. This variety of behaviour arises despite the resemblance of
      these three species in terms of electronic structure and gas phase dipole moment,
      emphasising the requirement for detailed chemical models of this phenomenon.

PMID- 23147678
TI  - The ER in 4D: a novel stress pathway controlling endoplasmic reticulum membrane
      remodeling.

PMID- 23147681
TI  - Unprecedented Dawson isomerism induced by a central [WO5] and four 45 degrees 
      rotated belt square pyramids.
AB  - The seventh type of Wells-Dawson isomer, delta-[(WO(5))W(17)Cu(H(2)O)O(55)](10-)
      (1a) was obtained as a consequence of the formation of the first central square
      pyramidal [WO(5)] moiety that results in a 45 degrees  rotation of the four belt
      [CuO(5)]/[WO(5)] square pyramids, establishing a new type of WD isomerism
      involving the rotation of the belt polyhedra, that were previously believed to
      stay unchanged.

PMID- 23147682
TI  - Dietary beta-carotene regulates interleukin-1beta-induced expression of
      apolipoprotein E in astrocytes isolated from stroke-prone spontaneously
      hypertensive rats.
AB  - Stroke-prone spontaneously hypertensive rats (SHRSP) have an abnormality in
      cholesterol synthesis, but the pathological relevance of this to stroke and
      related neuronal disorders is not yet clear. The induction of astrocyte-derived
      cholesterol transportation to neurons by apolipoprotein E (apoE) promotes
      neuronal repair after brain injuries such as stroke. Such repair is reduced by
      interleukin-1 beta (IL-1beta) and stroke conditions. Furthermore, fibroblast
      growth factor 1 (FGF1) regulates the production of apoE-cholesterol-rich high
      density lipoproteins (HDL) and induces gliosis of astrocytes. On the other hand,
      high levels of plasma carotenoids reduce the risk of ischemic stroke. Thus, we
      investigated the expression of apoE in primary astrocytes that had been treated
      with IL-1beta or beta-carotene. In addition, we compared the expression levels of
      Apoe genes in astrocytes from SHRSP/Izm and normal control rats, Wistar-Kyoto
      rats (WKY/Izm) following hypoxia/reoxygenation (H/R). The expression levels of
      genes and proteins were investigated by RT-PCR, Western blotting (WB), and
      immunofluorescence analysis. IL-1beta decreased the expression levels of the Apoe
      gene. Conversely, beta-carotene significantly enhanced the expression levels of
      genes related to cholesterol regulation, including Abca1, Abcg1, Hmgcr as well as
      Apoe. During H/R, the gene expression levels of Apoe were decreased in the
      SHRSP/Izm rats in comparison with the WKY/Izm rats. These results suggest that IL
      1beta decreases Apoe expression levels, whereas beta-carotene strongly elevates
      Apoe levels and inhibits FGF1-mediated gliosis of astrocytes. Furthermore, under
      hypoxic stress, astrocytes isolated from SHRSP/Izm rats displayed altered
      regulation of Apoe compared with those from WKY/Izm rats.

PMID- 23147683
TI  - Anoxic depolarization of hippocampal astrocytes: possible modulation by P2X7
      receptors.
AB  - Current responses from CA1 neurons and stratum oriens astrocytes were recorded
      from hippocampal brain slices by means of the whole-cell patch-clamp technique.
      Anoxic depolarization (AD) was induced by an oxygen/glucose-deprived (OGD) medium
      also containing sodium iodoacetate and antimycin, in order to block glycolysis
      and oxidative phosphorylation, respectively. Anoxic depolarization has been
      reported to be due to the sudden increase of the extracellular K(+) concentration
      and the accompanying explosive rise in glutamate concentration. We asked
      ourselves whether the release of ATP activating P2X7 receptors is also involved
      in the AD. Although, the AD was evoked in absolute synchrony in neurons and
      astrocytes, and the NMDA receptor antagonistic AP-5 depressed these responses,
      neither the non-selective P2 receptor antagonist PPADS, nor the highly selective
      P2X7 receptor antagonist A438079 interfered with the AD or its delay time in
      neurons/astrocytes after inducing chemical hypoxia. However, A438079, but not
      PPADS increased in astrocytes the slow inward current observed in a hypoxic
      medium. It is concluded that ATP co-released with glutamate by hypoxic
      stimulation has only a minor function in the present brain slice system.

PMID- 23147684
TI  - Clinical decision support to improve blood pressure control in hemodialysis
      patients: a nonrandomized controlled trial.
AB  - BACKGROUND: Computer-based clinical decision support aims to improve the quality
      of patient care. The utility of decision support for improving blood pressure
      control in hemodialysis patients is unknown. METHODS: This was a nonrandomized
      controlled trial of adult patients receiving chronic in-center hemodialysis
      during the period of April 1, 2005, to September 30, 2006, in 1 of the 2 major
      university-based renal programs in Alberta, Canada. Physicians in the
      intervention center were provided with twice-monthly audits and printed
      management suggestions based on guideline-recommended blood pressure targets. The
      same data were available to physicians in the control group but without audit and
      feedback decision support. RESULTS: Eight hundred and thirty hemodialysis
      patients were receiving dialysis treatment at the time the study was initiated.
      Preintervention and postintervention blood pressure data were available for 361
      patients. The primary outcome, the proportion of postdialysis systolic blood
      pressures at target over 12 months, did not differ between the intervention and
      the control programs (unadjusted odds ratio 0.59; 95% confidence interval [95%
      CI], 0.34-1.02, p = 0.06; adjusted odds ratio 0.62; 95% CI, 0.35-1.11, p = 0.11).
      There was no significant difference between the intervention and control groups
      in other measures of blood pressure such as the mean change in postdialysis
      systolic blood pressures (unadjusted mean difference 4 mm Hg, 95% CI, -1 to 9, p
      = 0.36; adjusted mean difference 2 mm Hg, 95% CI, -1 to 5, p = 0.19).
      CONCLUSIONS: In this population of chronic hemodialysis patients, a computer
      based clinical decision support system was not associated with improved blood
      pressure control.

PMID- 23147685
TI  - Ten-year patient survival on maintenance haemodialysis: association with
      treatment time and dialysis dose.
AB  - BACKGROUND: Analyses of national registry-based datasets have demonstrated the
      association of longer haemodialysis treatment times with lowered mortality risk.
      METHODS: We performed a prospective cohort study of 451 incident haemodialysis
      patients and examined the effect of targeting higher dialysis dose with extended
      treatment time, on 10-year patient outcomes. RESULTS: Mean treatment time (TT)
      was 233 +/- 22.8 minutes (median 235, range 180-296). Overall patient survival
      was 95% at 1 year, 75% at 3 years, 56% at 5 years and 25% at 10 years. Increasing
      TT was associated with incremental 10-year patient survival (TT >/=241 minutes
      39.7%, TT 226-240 minutes 19.6% and TT </=225 minutes 14.7%; p<0.001). Single
      pool Kt/V and TT were strong independent predictors of patient survival in Cox
      multivariate analysis (p<0.0001). At 10 years, each 0.1-unit increase in spKt/V
      and 20-minute increase in TT were associated with a 20% and 32% decrease in the
      relative risk of death, respectively. Survival benefits of higher dialysis dose
      and longer TT were cumulative, with highest survival exhibited by patients
      achieving both Kt/V >1.6 and TT >/=241 minutes, and lowest survival exhibited by
      patients receiving Kt/V <1.2 and TT </=225 minutes. CONCLUSION: Extended
      treatment times are associated with higher patient survival irrespective of
      dialysis dose. Further study of extended treatment time and effect on patient
      outcomes is needed.

PMID- 23147686
TI  - Relationship between hemorheology and endothelial dysfunction in renal transplant
      patients receiving calcineurin inhibitors.
AB  - BACKGROUND: Calcineurin inhibitors, mainly cyclosporin A (CsA), are associated
      with endothelial dysfunction in renal transplant recipients (RTRs).
      Hemorheological disturbances including decreased erythrocyte deformability (ED),
      increased plasma viscosity and erythrocyte aggregation (EA) have also been
      reported in CsA-treated RTRs. The aim of this study was to investigate the
      relationship between hemorheological factors and endothelial dysfunction in CsA-
      and tacrolimus (Tc)-treated RTRs. METHODS: Thirty-one RTRs and 16 healthy
      subjects were recruited. The RTR group received either CsA (n = 16) or Tc (n =
      15). Endothelial function was evaluated by flow-mediated dilation (FMD) of the
      brachial artery. ED and EA were measured with laser-assisted optical rotational
      cell analyzer, and plasma viscosity by a cone-plate viscometer. RESULTS: FMD of
      the CsA group was significantly lower than that of controls (6.3% +/- 5.1% vs.
      11.9% +/- 5.6%, p = 0.024), whereas, there was no significant difference between
      the Tc group (8.8% +/- 5.4%) and controls. At shear stresses ranging between 0.95
      and 30 Pa, EDs of the CsA group were significantly lower compared with controls.
      In the Tc group, the decrease in ED was significant at shear stresses ranging
      between 0.53 and 5.33 Pa. ED indices did not correlate with FMD in any of the
      groups. CONCLUSIONS: The degree of endothelial dysfunction and reduction in ED
      were more remarkable in patients on CsA therapy. Hemorheological factors were not
      likely to be associated with endothelial dysfunction in RTRs.

PMID- 23147687
TI  - Relationship between sRAGE and eotaxin-3 with CRP in hypertensive patients at
      high cardiovascular risk.
AB  - BACKGROUND: Cardiovascular disease (CVD) is the leading cause of death in Western
      countries and is highly prevalent in patients with kidney disease. Traditional
      risk factors for CVD often accompany kidney dysfunction, and chronic kidney
      disease per se is considered an additional risk factor. Risk stratification for
      CVD remains suboptimal even after the introduction of global risk assessment by
      various scores. This has prompted the search for novel markers of cardiovascular
      risk, and several biomarkers have been suggested as candidates, together with C
      reactive protein (CRP). The objective of the present study was to investigate the
      relationship between novel biomarkers of vascular inflammation (soluble form of
      the receptor for advanced glycation end products [sRAGE] and eotaxin-3) with CRP
      in a population of hypertensive patients at high cardiovascular risk. METHODS:
      Plasma sRAGE, high-sensitivity CRP (hs-CRP) and eotaxin-3 were measured in 399
      hypertensive patients (265 men, mean age 58 +/- 8 years)with diabetes mellitus,
      metabolic syndrome or organ damage. RESULTS: Plasma concentrations of sRAGE,
      eotaxin-3 and hs-CRP were not different between diabetic and nondiabetic
      subjects. Univariate analysis showed that plasma levels of sRAGE and eotaxin-3
      were not associated with hs-CRP in either subgroup. CONCLUSION: Our study
      confirms the robust and widely studied role of CRP as an important marker of
      vascular inflammation. We also postulate the possible involvement of sRAGE and
      eotaxin, 2 novel biomarkers, in CVDs. On the basis of our results, we can put
      forward the hypotheses that hs-CRP, s-RAGE and eotaxin are reliable but unrelated
      cardiovascular risk markers.

PMID- 23147688
TI  - Sodium setpoint and gradient in bicarbonate hemodialysis.
AB  - BACKGROUND: The demonstration of an individual osmolar setpoint in hemodialysis
      (HD) is crucial to individualize dialysate sodium concentrations. Furthermore,
      the diffusive gradient between plasma and dialysate sodium is important in the
      "fine tuning" of the intradialytic sodium mass balance (MB). METHODS: The design
      of this study included part A: a retrospective analysis of predialysis plasma
      sodium concentrations extracted from a 6-year database in our HD population (147
      prevalent white anuric patients); and part B: study of intradialytic sodium
      kinetics in 48 patients undergoing one 4-hour bicarbonate HD session. Direct
      potentiometry with an ion-selective electrode was used for sodium measurements.
      RESULTS: Study part A: the mean number of plasma sodium measurements per patient
      was 16.06 +/- 14.03 over a mean follow-up of 3.55 +/- 1.76 years. The mean of the
      averaged plasma sodium concentrations was 136.7 +/- 2.1 mmol/L, with a low mean
      intraindividual coefficient of variation (1.39 +/- 0.4). Study part B: mean
      predialysis and postdialysis plasma sodium concentrations were 135.8 +/- 0.9 and
      138.0 +/- 0.9 mmol/L (p<0.001). Mean inlet dialyzer sodium concentration was
      138.7 +/- 1.1 mmol/L; the hourly diffusion concentration gradients showed a
      statistically significant transfer from dialysate to plasma (Wilks ? <0.0001). A
      statistically significant relationship was found between sodium MB and diffusion
      gradient (p<0.02), and between sodium MB and ultrafiltration volume (p<0.01).
      CONCLUSIONS: A relatively "fixed" and individual osmolar setpoint in HD patients
      was shown for the first time in a long-term follow-up. A dialysate sodium
      concentration of 140 mmol/L determined a dialysate to plasma sodium gradient.

PMID- 23147689
TI  - Beta blockers therapy is associated with improved left ventricular systolic
      function and sustained exercise capacity in elderly patients with heart failure.
      CIBIS-ELD sub-study.
AB  - BACKGROUND: Exercise capacity is critical for therapy and prognosis in patients
      with heart failure (HF). Effect of beta-blockers (BB) on exercise capacity in
      elderly patients with HF remains unclear. OBJECTIVES: To assess contribution of
      BB to functional capacity and left ventricular (LV) function in the elderly with
      HF. DESIGN: According to the protocol of CIBIS-ELD study group, elderly patients
      were treated with BB during 12 weeks. In CPET subgroup, an integral part of the
      CIBIS ELD study group, patients were performed Doppler echocardiography and
      cardiopulmonary exercise testing (CPET) before BB therapy and after 12 weeks.
      SETTING: Randomized patients with HF beta blockers naive. PARTICIPANTS: thirty
      patients with HF aged over 65 years were included in CPET subgroup, while 847
      were incorporated in CIBIS ELD study group. RESULTS: Heart rate (HR) and systolic
      blood pressure (SBP) after BB significantly decreased at rest (p<0.001) and
      during exercise (p<0.05), with sustained level of peak VO2. Observed changes of
      resting HR and peak HR were closely correlated (p<0.001). Significant improvement
      of LV ejection fraction after BB was obtained (p=0.003) and symptoms of
      breathlessness were reduced (p=0.001). Left ventricular diastolic dysfunction at
      rest significantly contributed to exercise capacity (p=0.019). CONCLUSIONS: Beta
      blockers in elderly patients with HF are related to a significant decrease of HR
      and SBP, improvement of systolic LV function and sustained exercise tolerance.
      Resting LV diastolic dysfunction is strongly associated with lower exercise
      capacity.

PMID- 23147691
TI  - Chronic delivery of low-level exogenous current preserves retinal function in
      pigmented P23H rat.
AB  - Diffuse electrical currents delivered to the eye were investigated in a rat model
      of retinitis pigmentosa for potentially therapeutic effects. Low-level currents
      were passed between electrodes placed on the cornea and in the mouth during 30
      min sessions two times per week from 4 to 16 weeks of age. Single-flash
      electroretinograms (ERG) were recorded and analyzed for amplitude and measures of
      sensitivity, and basic histology was performed. ERG a-wave amplitudes were
      slightly greater in treated vs. age-matched controls at 16 weeks of age, but the
      combined thicknesses of the outer nuclear layer and outer segment layer were
      similar at this age. Treated animals exhibited a significant preservation of b
      wave amplitudes, and a striking preservation of rod sensitivity, measured as the
      stimulus strength required to reach half-saturation of the a-wave. Analysis of
      the leading edge of the a-wave using a delayed Gaussian function revealed a
      decrease in the parameter reflecting gain of the phototransduction cascade over
      the 12-week course of treatment, and no significant change in control animals
      over the same period. These results suggest that while the exogenous currents
      failed to preserve the number or gross structure of rods, the responsivity of
      individual photoreceptors was relatively preserved, perhaps via an increase in
      efficiency of photon capture (R/photon). This preserved functionality may delay
      the retraction of bipolar cell dendrites from degenerating photoreceptors.

PMID- 23147690
TI  - Adaptive deployment of spatial and feature-based attention before saccades.
AB  - What you see depends not only on where you are looking but also on where you will
      look next. The pre-saccadic attention shift is an automatic enhancement of visual
      sensitivity at the target of the next saccade. We investigated whether and how
      perceptual factors independent of the oculomotor plan modulate pre-saccadic
      attention within and across trials. Observers made saccades to one (the target)
      of six patches of moving dots and discriminated a brief luminance pulse (the
      probe) that appeared at an unpredictable location. Sensitivity to the probe was
      always higher at the target's location (spatial attention), and this attention
      effect was stronger if the previous probe appeared at the previous target's
      location. Furthermore, sensitivity was higher for probes moving in directions
      similar to the target's direction (feature-based attention), but only when the
      previous probe moved in the same direction as the previous target. Therefore,
      implicit cognitive processes permeate pre-saccadic attention, so that-contingent
      on recent experience-it flexibly distributes resources to potentially relevant
      locations and features.

PMID- 23147692
TI  - A practical quantification method for Heinz bodies in birds applicable to rapid
      response field scenarios.
AB  - Oil-induced oxidative injury to red blood cells results in Heinz body hemolytic
      anemia. Here, we evaluated three Heinz body staining techniques in brown pelican
      (Pelecanus occidentalis) blood. Using a range of in vitro acetylphenylhydrazine
      incubations, we validated a field-adapted technique against laboratory wet-mounts
      and verified the stability of this technique for one month following preparation.
      Employing this technique during petrochemical spill responses allows for delays
      between sample collection and analysis.

PMID- 23147695
TI  - CNI-1493 attenuates neuroinflammation and dopaminergic neurodegeneration in the
      acute MPTP mouse model of Parkinson's disease.
AB  - BACKGROUND: Parkinson's disease (PD) is associated with neurodegeneration of
      dopaminergic neurons in the substantia nigra. Neuroinflammatory processes have
      been shown to be a key component of this neurodegeneration and, as such, small
      molecule compounds which inhibit these inflammatory events are a critical
      research focus. OBJECTIVE: CNI-1493 is an anti-inflammatory compound that
      strongly inhibits macrophages and also stimulates the cholinergic anti
      inflammatory pathway. We have examined whether CNI-1493 has a neuroprotective
      effect in the acute 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse
      model of PD. METHODS: CNI-1493 (8 mg/kg i.p.) or placebo administration was
      started 1 day before MPTP intoxication and repeated daily until sacrifice after
      MPTP intoxication. C57/Bl6 mice - either treated with CNI-1493 or with placebo -
      were injected intraperitoneally 4 times at 2-hour intervals with either 20 mg/kg
      MPTP-HCl or a corresponding volume of saline. Two or 7 days after the end of the
      MPTP intoxication, the animals were killed and their brains were processed for
      further analysis. RESULTS: Administration of CNI-1493 markedly protected tyrosine
      hydroxylase-positive substantia nigra neurons against MPTP neurotoxicity. CNI
      1493 treatment in the MPTP model was also accompanied by a profound reduction of
      activated microglia within the substantia nigra, as measured by ionized calcium
      binding adapter molecule-1 staining. CONCLUSIONS: These findings support that CNI
      1493 could reduce the MPTP-induced toxicity likely by inhibition of
      neuroinflammatory responses. The neuroprotective effect of CNI-1493 suggests that
      CNI-1493 might be a valuable neuroprotective candidate in the future treatment of
      PD.

PMID- 23147696
TI  - Effect of oral JTT-751 (ferric citrate) on hyperphosphatemia in hemodialysis
      patients: results of a randomized, double-blind, placebo-controlled trial.
AB  - BACKGROUND/AIMS: JTT-751 (ferric citrate hydrate) is a novel oral, iron-based
      phosphate binder being developed for the treatment of hyperphosphatemia among
      chronic kidney disease patients who are on dialysis. This study investigated the
      dose-response and safety of JTT-751 among Japanese hemodialysis patients.
      METHODS: This was a multicenter, randomized, placebo-controlled, double-blind,
      parallel-group, comparative study. A total of 192 subjects with serum phosphorus
      (P) levels between 6.1 and 10.0 mg/dl were randomized to JTT-751 (1.5, 3 or 6
      g/day) or to placebo treatment for 28 days. Changes in serum P level from
      baseline were examined. RESULTS: In the full analysis set, the mean change in
      serum P level at week 4 was 0.04, -1.28, -2.16 and -4.10 mg/dl in the placebo,
      1.5-grams, 3-grams and 6-grams/day groups, respectively, demonstrating a dose
      response relationship up to 6 g/day. Overall, a reduction in serum P levels to
      <=5.5 mg/dl was achieved in 2.5, 16.7, 50.0 and 92.6% of subjects, in the
      placebo, 1.5-grams, 3-grams and 6-grams/day groups, respectively. The most common
      adverse events (AEs) were gastrointestinal disorders. Most AEs were mild. In 25
      patients, treatment was discontinued due to increased transferrin saturation
      >=50%; however, this was not considered to be a safety issue. CONCLUSIONS: When
      hemodialysis subjects received JTT-751 at doses between 1.5 and 6 g/day for 28
      days, serum P levels were significantly reduced in a dose-dependent manner (p <
      0.001). JTT-751 was found to be efficacious and safe, with the majority of
      subjects in the 6-grams/day group achieving a serum P level of <=5.5 mg/dl.

PMID- 23147697
TI  - Essential role of phosphines in organocatalytic beta-boration reaction.
AB  - The use of phosphines to assist the organocatalytic beta-boration reaction of
      alpha,beta-unsaturated carbonyl compounds has been demonstrated with a selected
      number of substrates. The new method eludes the use of Bronsted bases to promote
      the catalytic active species and PR(3) becomes essential to interact with the
      substrate resulting in the formation of a zwitterionic phosphonium enolate. This
      species can further deprotonate MeOH when B(2)pin(2) is present forming
      eventually the ion pair [alpha-(H),beta-(PR(3))-ketone](+)[B(2)pin(2).MeO](-)
      that is responsible for the catalysis.

PMID- 23147698
TI  - Capillary electrophoretic separation-based approach to determine the labeling
      kinetics of oligodeoxynucleotides.
AB  - With the recent advances in electron microscopy (EM), computation, and
      nanofabrication, the original idea of reading DNA sequence directly from an image
      can now be tested. One approach is to develop heavy atom labels that can provide
      the contrast required for EM imaging. While evaluating tentative labels for the
      respective nucleobases in synthetic oligodeoxynucleotides (oligos), we developed
      a streamlined CE protocol to assess the label stability, reactivity, and
      selectivity. We report our protocol using osmium tetroxide 2,2'-bipyridine
      (Osbipy) as a thymidine (T) specific label. The observed rates show that the
      labeling process is kinetically independent of both the oligo length, and the
      base composition. The conditions, i.e. temperature, optimal Osbipy concentration,
      and molar ratio of reagents, to promote 100% conversion of the starting oligo to
      labeled product were established. Hence, the optimized conditions developed with
      the oligos could be leveraged to allow osmylation of effectively all Ts in ssDNA,
      while achieving minimal mislabeling. In addition, the approach and methods
      employed here may be adapted to the evaluation of other prospective contrasting
      agents/labels to facilitate next-generation DNA sequencing by EM.

PMID- 23147699
TI  - Association of genetic polymorphisms in ERCC1 and ERCC2/XPD with risk of chronic
      benzene poisoning in a Chinese occupational population.
AB  - DNA damage induced by benzene and its metabolites is thought of as an important
      mechanism underlying benzene genotoxicity in chronic benzene poisoning (CBP).
      Therefore, genetic variation in DNA repair genes may contribute to susceptibility
      to CBP in the exposed population. Since benzene-induced DNA damages include DNA
      adducts, we hypothesized that the polymorphisms of ERCC1 (Excision repair cross
      complementation group 1) and ERCC2/XPD (Excision repair cross complementation
      group 2/xeroderma pigmentosum group D) are associated with the risk of CBP. A
      case-control study involving 102 benzene-poisoned patients and 204 none-benzene
      poisoned controls occupationally exposed to benzene was carried out in the
      Northeast region of China. The polymorphisms of codon 118 (rs11615) and C8092A
      (rs3212986) of ERCC1, codon 751 (rs13181), 312 (rs1799793) and 156 (rs238406) of
      ERCC2/XPD were genotyped by TaqMan((r)) Real-time PCR. The results showed that
      individuals carrying the ERCC1 codon 118 TT genotype had an increased risk of CBP
      (OR(adj)=3.390; 95%CI: 1.393-8.253; P=0.007) comparing with its CC genotype.
      After stratified by smoking, gender and exposure duration we found that the
      increased risk of CBP associated with the ERCC1 codon 118 TT genotype confined to
      nonsmokers (OR=3.214; 95% CI: 1.359-7.601; P=0.006), female (OR=3.049; 95% CI:
      1.235-7.529; P=0.013) and exposure duration> 12 years (OR=3.750; 95% CI: 1.041
      13.513; P=0.035). Since ERCC1 and ERCC2/XPD are both located on chromosome
      19q13.3, haplotype analysis of all 5 SNPs was also conducted. However no
      correlations between the risks of CBP and other genotypes or haplotypes were
      found. Therefore, our findings suggest an important role of ERCC1 codon 118
      polymorphisms for a biomarker to CBP in the Chinese occupational population.

PMID- 23147700
TI  - Genotoxic and mutagenic effects of lipid-coated CdSe/ZnS quantum dots.
AB  - We proposed to evaluate the genotoxicity and mutagenicity of a new quantum dots
      (QDs) nanoplatform (QDsN), consisting of CdSe/ZnS core-shell QDs encapsulated by
      a natural fusogenic lipid (1,2-di-oleoyl-sn-glycero-3-phosphocholine (DOPC)) and
      functionalized by a nucleolipid N-[5'-(2',3'-di-oleoyl) uridine]-N',N',N'
      trimethylammoniumtosylate (DOTAU). This QDs nanoplatform may represent a new
      therapeutic tool for the diagnosis and treatment of human cancers. The genotoxic,
      mutagenic and clastogenic effects of QDsN were compared to those of cadmium
      chloride (CdCl(2)). Three assays were used: (1) the Salmonella/microsome assay
      with four tester strains, (2) the comet assay and (3) the micronucleus test on
      CHO cells. The contribution of simulated sunlight was studied in the three assays
      while oxidative events were only explored in the comet assay in aliquots
      pretreated with the antioxidant l-ergothioneine. We found that QDsN could enter
      CHO-K1 cells and accumulate in cytoplasmic vesicles. It was not mutagenic in the
      Salmonella/mutagenicity test whereas CdCl(2) was weakly positive. In the dark,
      both the QDsN and CdCl(2) similarly induced dose-dependent increases in single
      strand breaks and micronuclei. Exposure to simulated sunlight significantly
      potentiated the genotoxic activities of both QDsN and CdCl(2), but did not
      significantly increase micronucleus frequencies. l-Ergothioneine significantly
      reduced but did not completely suppress the DNA-damaging activity of QDsN and
      CdCl(2). The present results clearly point to the genotoxic properties and the
      risk of long-term adverse effects of such a nanoplatform if used for human
      anticancer therapy and diagnosis in the future.

PMID- 23147704
TI  - Bacterial physiology: Caulobacter chooses to self-destruct.

PMID- 23147703
TI  - Rethinking vector immunology: the role of environmental temperature in shaping
      resistance.
AB  - Recent ecological research has revealed that environmental factors can strongly
      affect insect immunity and influence the outcome of host-parasite interactions.
      To date, however, most studies examining immune function in mosquitoes have
      ignored environmental variability. We argue that one such environmental variable,
      temperature, influences both vector immunity and the parasite itself. As
      temperatures in the field can vary greatly from the ambient temperature in the
      laboratory, it will be essential to take temperature into account when studying
      vector immunology.

PMID- 23147706
TI  - Environmental microbiology: bacterial power lines.

PMID- 23147705
TI  - The industrial evolution.
AB  - This month's Genome Watch highlights new insights into the use of bacteria in
      industrial processes such as electricity generation and bioremediation.

PMID- 23147702
TI  - Adaptation of Pseudomonas aeruginosa to the cystic fibrosis airway: an
      evolutionary perspective.
AB  - The airways of patients with cystic fibrosis (CF) are nearly always infected with
      many different microorganisms. This environment offers warm, humid and nutrient
      rich conditions, but is also stressful owing to frequent antibiotic therapy and
      the host immune response. Pseudomonas aeruginosa is commonly isolated from the
      airways of patients with CF, where it most often establishes chronic infections
      that usually persist for the rest of the lives of the patients. This bacterium is
      a major cause of mortality and morbidity and has therefore been studied
      intensely. Here, we discuss how P. aeruginosa evolves from a state of early,
      recurrent intermittent colonization of the airways of patients with CF to a
      chronic infection state, and how this process offers opportunities to study
      bacterial evolution in natural environments. We believe that such studies are
      valuable not only for our understanding of bacterial evolution but also for the
      future development of new therapeutic strategies to treat severe chronic
      infections.

PMID- 23147707
TI  - Bacterial secretion: Sec and Tat collaborate in a Rieske business.

PMID- 23147709
TI  - Phage biology: phage plays copycat with ToxIN.

PMID- 23147710
TI  - Viral pathogenesis: SIV gives the virome a boost.

PMID- 23147708
TI  - Knowing your friends: invertebrate innate immunity fosters beneficial bacterial
      symbioses.
AB  - The innate immune system is present in all animals and is a crucial first line of
      defence against pathogens. However, animals also harbour large numbers of
      beneficial microorganisms that can be housed in the digestive tract, in
      specialized organs or on tissue surfaces. Although invertebrates lack
      conventional antibody-based immunity, they are capable of eliminating pathogens
      and, perhaps more importantly, discriminating them from other microorganisms.
      This Review examines the interactions between the innate immune systems of
      several model invertebrates and the symbionts of these organisms, and addresses
      the central question of how these long-lived and specific associations are
      established and maintained.

PMID- 23147711
TI  - Reduction of miscarriages through universal screening and treatment of thyroid
      autoimmune diseases.
AB  - BACKGROUND/AIMS: Universal screening for thyroid diseases during pregnancy is
      controversial. Targeted screening does not identify all women with thyroid
      dysfunction. Furthermore, antithyroid peroxidase antibodies (TPOAb) are suspected
      to be associated with an increased risk of fetal loss, premature delivery and
      hypothyroidism. The aim of our study was to assess the rationale behind universal
      screening and propose thyroxine treatment in particular cases. METHODS: Between
      January 2008 and May 2009, 537 consecutive iodine-supplemented women with a
      singleton pregnancy [441 TPOAb- controls and 96 TPOAb+ women (47 nontreated and
      49 treated)] were evaluated using thyroid and obstetric parameters. According to
      our algorithm for thyroid screening in pregnancy, if thyroid-stimulating hormone
      (TSH) exceeded 1 mU/l in TPOAb+ women, 50 ug of levothyroxine (L-T4) was
      prescribed. RESULTS: The miscarriage rate was significantly higher in the
      nontreated TPOAb+ group compared with the treated group (16 vs. 0%; p = 0.02).
      Compared to the control group, TSH in TPOAb+ patients was higher at the first
      prenatal visit prior to L-T4 treatment (p < 0.01), while free thyroxine was
      higher than in the control group after the 20th week (p < 0.05). CONCLUSIONS: Our
      study supports the potential benefit of universal screening and L-T4 treatment
      for autoimmune thyroid disease during pregnancy. Efforts are still needed to
      further decrease miscarriage rates.

PMID- 23147712
TI  - Mating-relevant olfactory stimuli activate the rat brain in an age-dependent
      manner.
AB  - Chemosensory stimulation is vital for the expression of rodent sexual behavior.
      As sexual activity decreases with aging, this study investigated whether aging
      also impacts the integration of sex-relevant chemosensory cues. To this end,
      several measures were obtained from adult (10-12 months) and aged (30-36 months)
      male rats after exposure to a conspecific estrous female. These included rates of
      investigatory behaviors, levels of stimulus-induced Fos immunoreactivity,
      activation of gonadotropin-releasing hormone-containing cells, and levels of
      circulating testosterone and corticosterone. The results indicated no significant
      differences in investigatory behaviors, levels of corticosterone, or activation
      of gonadotropin-releasing hormone-containing cells between the two groups. As has
      been reported previously, the levels of testosterone were lower in the aged rats.
      However, stimulus-induced neural activity was higher in the bed nucleus of the
      stria terminalis and the medial preoptic area of aged rats, whereas no
      differences were found in the main olfactory bulb, accessory olfactory bulb,
      medial amygdala, ventral tegmental area, or nucleus accumbens. These findings
      suggest the presence of a compensatory mechanism in the hypothalamus of aged
      animals versus adults, whereby more cells are recruited to elicit a sexual
      response in the presence of a sexually exciting stimulus.

PMID- 23147713
TI  - Fecundity of patients with schizophrenia, autism, bipolar disorder, depression,
      anorexia nervosa, or substance abuse vs their unaffected siblings.
AB  - CONTEXT: It is unknown how genetic variants conferring liability to psychiatric
      disorders survive in the population despite strong negative selection. However,
      this is key to understanding their etiology and designing studies to identify
      risk variants. OBJECTIVES: To examine the reproductive fitness of patients with
      schizophrenia and other psychiatric disorders vs their unaffected siblings and to
      evaluate the level of selection on causal genetic variants. DESIGN: We measured
      the fecundity of patients with schizophrenia, autism, bipolar disorder,
      depression, anorexia nervosa, or substance abuse and their unaffected siblings
      compared with the general population. SETTING: Population databases in Sweden,
      including the Multi-Generation Register and the Swedish Hospital Discharge
      Register. PARTICIPANTS: In total, 2.3 million individuals among the 1950 to 1970
      birth cohort in Sweden. MAIN OUTCOME MEASURES: Fertility ratio (FR), reflecting
      the mean number of children compared with that of the general population,
      accounting for age, sex, family size, and affected status. RESULTS: Except for
      women with depression, affected patients had significantly fewer children (FR
      range for those with psychiatric disorder, 0.23-0.93; P < 10-10). This reduction
      was consistently greater among men than women, suggesting that male fitness was
      particularly sensitive. Although sisters of patients with schizophrenia and
      bipolar disorder had increased fecundity (FR range, 1.02-1.03; P < .01), this was
      too small on its own to counterbalance the reduced fitness of affected patients.
      Brothers of patients with schizophrenia and autism showed reduced fecundity (FR
      range, 0.94-0.97; P < .001). Siblings of patients with depression and substance
      abuse had significantly increased fecundity (FR range, 1.01-1.05; P < 10-10). In
      the case of depression, this more than compensated for the lower fecundity of
      affected individuals. CONCLUSIONS: Our results suggest that strong selection
      exists against schizophrenia, autism, and anorexia nervosa and that these
      variants may be maintained by new mutations or an as-yet unknown mechanism.
      Bipolar disorder did not seem to be under strong negative selection.
      Vulnerability to depression, and perhaps substance abuse, may be preserved by
      balancing selection, suggesting the involvement of common genetic variants in
      ways that depend on other genes and on environment.

PMID- 23147715
TI  - Gamma-radiation induced formation of chromium oxide nanoparticles from dissolved
      dichromate.
AB  - The formation of chromium oxide nanoparticles by gamma radiolysis of Cr(VI)
      (CrO(4)(2-) or Cr(2)O(7)(2-)) solutions was investigated as a function of pH and
      initial Cr(VI) concentration by measuring [Cr(VI)], the particle concentration
      ([Cr(III)(col)]) and [H(2)], and by characterizing the particles using TEM,
      Raman, FTIR and XPS. The results show that Cr(VI) is easily reduced to Cr(III) by
      a homogeneous aqueous reaction with e(aq)(-), but, due to the stability of
      Cr(III) colloids, the growth of the Cr(OH)(3) particles is very slow. As the
      particles grow the interior of the particle dehydrates to form Cr(2)O(3) while
      the outer layer remains hydrated. When most of the Cr(VI) that is initially
      present in the solution is converted to Cr(OH)(3) further redox reactions of
      chromium species occur on the particle surfaces. The redox system reaches a
      pseudo-equilibrium state due to cyclic reactions of Cr(III) with OH and H(2)O(2),
      and reactions of Cr(VI) with e(aq)(-) and H(2)O(2). The size distribution of the
      particles that are formed is controlled by these solution-solid interface
      reactions.

PMID- 23147714
TI  - Baicalin and scutellarin are proteasome inhibitors that specifically target
      chymotrypsin-like catalytic activity.
AB  - Baicalin and scutellarin are the major active principal flavonoids extracted from
      the Chinese herbal medicines Scutellaria baicalensis and Erigeron breviscapus
      (Vant.) Hand-Mazz. It has recently been reported that baicalin and scutellarin
      have antitumor activity. However, the mechanisms of action are unknown. We
      previously reported that some flavonoids have a specific role in the inhibition
      of the activity of proteasome subunits and induced apoptosis in tumor cells. To
      further investigate these pharmacological effects, we examined the inhibitory
      activity of baicalin and scutellarin on the extracted proteasomes from mice and
      cancer cells. Using fluorogenic substrates for proteasome catalytic subunits, we
      found that baicalin and scutellarin specifically inhibited chymotrypsin-like
      activity but did not inhibit trypsin-like and peptidyl-glutamyl peptide
      hydrolyzing activities. These data suggested that baicalin and scutellarin
      specifically inhibit chymotrypsin-like catalytic activity in the proteasome.

PMID- 23147716
TI  - Neutral tetrathia[22]annulene[2.1.2.1] based field-effect transistors: improved
      on/off ratio defies ring puckering.
AB  - New, neutral, slightly puckered aromatic meso-substituted
      tetrathia[22]annulene[2.1.2.1] macrocyclic architectures display p-type
      semiconductor behaviour and constitute molecular field-effect transistors with
      high on/off ratios (8.67 * 10(6)) and high mobility (0.23 cm(2) V(-1) s(-1)) in
      thin films deposited on octadecyltrichlorosilane (OTS) modified SiO(2).

PMID- 23147717
TI  - Influence of FMO1 and 3 polymorphisms on serum olanzapine and its N-oxide
      metabolite in psychiatric patients.
AB  - The widely used antipsychotic drug, olanzapine (OLA) shows large interindividual
      variability in metabolic clearance. Although the role of the enzymes CYP1A2,
      CYP2D6 and UGT1A4 has been extensively explored, little is known about the in
      vivo role of flavin-containing monooxygenases (FMOs) catalyzing the N-oxidation
      of OLA in vitro. We investigated the influence of FMO1 and 3 polymorphisms on the
      steady state serum concentrations of OLA and its N-oxide metabolite in 379
      patients. The upstream FMO1*6 was associated with increased dose-adjusted serum
      OLA concentrations (C/Ds; P=0.008), an effect further enhanced by FMO1rs7877C>T
      in smokers. The influence of FMO3 polymorphisms was limited to variability in OLA
      N-oxide. Homozygous carriers of FMO3rs2266780A>G (p.E308G) displayed 50% lower
      C/D of OLA N-oxide compared with subjects homo- or heterozygous for the A-variant
      (P<0.003). Our data support the role of FMO3 in the N-oxidation of OLA and
      implicate for the first time the contribution of FMO1 and its functional *6
      variant in OLA disposition. 

PMID- 23147718
TI  - Screening for distress, the sixth vital sign, in lung cancer patients: effects on
      pain, fatigue, and common problems--secondary outcomes of a randomized controlled
      trial.
AB  - BACKGROUND: This randomized controlled trial examined the impact of an online
      routine screening for distress program on physical symptoms and common
      psychosocial and practical problems in lung cancer outpatients. METHOD: Patients
      were randomly assigned to either the minimal screening group (the Distress
      Thermometer plus usual care); full screening group (Distress Thermometer,
      Canadian Problem Checklist (CPC), Pain Thermometer, Fatigue Thermometer, and the
      Psychological Screen for Cancer Part C, with a personalized report summarizing
      concerns); or triage (full screening plus option of personalized phone triage).
      Outcomes included pain, fatigue and psychosocial, practical and physical
      problems. Patients were reassessed 3 months later. RESULTS: A total of 549 lung
      patients completed baseline measures (89% of eligible patients) and 65.9% were
      retained at 3 months. At 3 months follow-up, significantly fewer patients in the
      triage group (32.1%) reported pain compared with the minimal screening group
      (49.6%), but the triage and full screening groups were not significantly
      different from one another. Patients in the triage group reported fewer problems
      with coping compared with the minimal and full screening groups and fewer
      problems with family conflict compared with the minimal screening group. Full
      screening patients reported fewer problems with breathlessness compared with the
      minimal screening group. No differences were found among groups in fatigue.
      Referrals were not associated with changes in outcomes over time. CONCLUSIONS:
      Routine screening for distress followed by personalized triage resulted in the
      most benefit for lung patients, with fewer fully screened and triaged patients
      reporting physical symptoms and psychosocial problems than those only minimally
      screened.

PMID- 23147719
TI  - Type 1 interferon-associated necroptosis: a novel mechanism for Salmonella
      enterica Typhimurium to induce macrophage death.

PMID- 23147721
TI  - Chlorhexidine and mupirocin susceptibilities of methicillin-resistant
      staphylococcus aureus from colonized nursing home residents.
AB  - Chlorhexidine and mupirocin are used in health care facilities to eradicate
      methicillin-resistant Staphylococcus aureus (MRSA) carriage. The objective of
      this study was to assess the frequency of chlorhexidine and mupirocin resistance
      in isolates from nares carriers in multiple nursing homes and to examine
      characteristics associated with resistance. Nasal swab samples were collected
      from approximately 100 new admissions and 100 current residents in 26 nursing
      homes in Orange County, CA, from October 2008 to May 2011. MRSA isolates were
      tested for susceptibility by using broth microdilution, disk diffusion, and
      Etest; for genetic relatedness using pulsed-field gel electrophoresis; and for
      qac gene carriage by PCR. Characteristics of the nursing homes and their
      residents were collected from the Medicare Minimum Data Set and Long-Term Care
      Focus. A total of 829 MRSA isolates were obtained from swabbing 3,806 residents
      in 26 nursing homes. All isolates had a chlorhexidine MIC of <=4 MUg/ml. Five
      (0.6%) isolates harbored the qacA and/or qacB gene loci. Mupirocin resistance was
      identified in 101 (12%) isolates, with 78 (9%) isolates exhibiting high-level
      mupirocin resistance (HLMR). HLMR rates per facility ranged from 0 to 31%. None
      of the isolates with HLMR displayed qacA or qacB, while two isolates carried qacA
      and exhibited low-level mupirocin resistance. Detection of HLMR was associated
      with having a multidrug-resistant MRSA isolate (odds ratio [OR], 2.69; P =
      0.004), a history of MRSA (OR, 2.34; P < 0.001), and dependency in activities of
      daily living (OR, 1.25; P = 0.004). In some facilities, HLMR was found in nearly
      one-third of MRSA isolates. These findings may have implications for the
      increasingly widespread practice of MRSA decolonization using intranasal
      mupirocin.

PMID- 23147720
TI  - Multifunctional immune responses of HMBPP-specific Vgamma2Vdelta2 T cells in M.
      tuberculosis and other infections.
AB  - Vgamma2Vdelta2 T (also known as Vgamma9Vdelta2 T) cells exist only in primates,
      and in humans represent a major gammadelta T-cell sub-population in the total
      population of circulating gammadelta T cells. Results from recent studies suggest
      that while (E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate (HMBPP) phosphoantigen
      from Mycobacterium tuberculosis (Mtb) and other microbes activates and expands
      primate Vgamma2Vdelta2 T cells, the Vgamma2Vdelta2 T-cell receptor (TCR)
      recognizes and binds to HMBPP on antigen-presenting cells (APC). In response to
      HMBPP stimulus, Vgamma2Vdelta2 TCRs array to form signaling-related nanoclusters
      or nanodomains during the activation of Vgamma2Vdelta2 T cells. Primary
      infections with HMBPP-producing pathogens drive the evolution of multieffector
      functional responses in Vgamma2Vdelta2 T cells, although Vgamma2Vdelta2 T cells
      display different patterns of responses during the acute and chronic phases of
      Mtb infection and in other infections. Expanded Vgamma2Vdelta2 T cells in primary
      Mtb infection can exhibit a broader TCR repertoire and a greater clonal response
      than previously assumed, with different distribution patterns of Vgamma2Vdelta2 T
      cell clones in lymphoid and non-lymphoid compartments. Emerging in vivo data
      suggest that HMBPP activation of Vgamma2Vdelta2 T cells appears to impact other
      immune cells during infection.

PMID- 23147722
TI  - Mechanism-based model of parasite growth and dihydroartemisinin pharmacodynamics
      in murine malaria.
AB  - Murine models are used to study erythrocytic stages of malaria infection, because
      parasite morphology and development are comparable to those in human malaria
      infections. Mechanism-based pharmacokinetic-pharmacodynamic (PK-PD) models for
      antimalarials are scarce, despite their potential to optimize antimalarial
      combination therapy. The aim of this study was to develop a mechanism-based
      growth model (MBGM) for Plasmodium berghei and then characterize the
      parasiticidal effect of dihydroartemisinin (DHA) in murine malaria (MBGM-PK-PD).
      Stage-specific (ring, early trophozoite, late trophozoite, and schizont) parasite
      density data from Swiss mice inoculated with Plasmodium berghei were used for
      model development in S-ADAPT. A single dose of intraperitoneal DHA (10 to 100
      mg/kg) or vehicle was administered 56 h postinoculation. The MBGM explicitly
      reflected all four erythrocytic stages of the 24-hour P. berghei life cycle.
      Merozoite invasion of erythrocytes was described by a first-order process that
      declined with increasing parasitemia. An efflux pathway with subsequent return
      was additionally required to describe the schizont data, thus representing
      parasite sequestration or trapping in the microvasculature, with a return to
      circulation. A 1-compartment model with zero-order absorption described the PK of
      DHA, with an estimated clearance and distribution volume of 1.95 liters h(-1) and
      0.851 liter, respectively. Parasite killing was described by a turnover model,
      with DHA inhibiting the production of physiological intermediates (IC(50), 1.46
      ng/ml). Overall, the MBGM-PK-PD described the rise in parasitemia, the nadir
      following DHA dosing, and subsequent parasite resurgence. This novel model is a
      promising tool for studying malaria infections, identifying the stage specificity
      of antimalarials, and providing insight into antimalarial treatment strategies.

PMID- 23147723
TI  - Clonal composition and community clustering of drug-susceptible and -resistant
      Escherichia coli isolates from bloodstream infections.
AB  - Multidrug-resistant Escherichia coli strains belonging to a single lineage
      frequently account for a large proportion of extraintestinal E. coli infections
      in many parts of the world. However, limited information exists on the community
      prevalence and clonal composition of drug-susceptible E. coli strains. Between
      July 2007 and September 2010, we analyzed all consecutively collected Gram
      negative bacterial isolates from patients with bloodstream infection (BSI)
      admitted to a public hospital in San Francisco for drug susceptibility and
      associated drug resistance genes. The E. coli isolates were genotyped for fimH
      single nucleotide polymorphisms (SNPs) and multilocus sequence types (MLSTs).
      Among 539 isolates, E. coli accounted for 249 (46%); 74 (30%) of them were
      susceptible to all tested drugs, and 129 (52%) were multidrug resistant (MDR).
      Only five MLST genotypes accounted for two-thirds of the E. coli isolates; the
      most common were ST131 (23%) and ST95 (18%). Forty-seven (92%) of 51 ST131
      isolates, as opposed to only 8 (20%) of 40 ST95 isolates, were MDR (P < 0.0001).
      The Simpson's diversity index for drug-susceptible ST genotypes was 87%, while
      the index for MDR ST genotypes was 81%. ST95 strains were comprised of four fimH
      types, and one of these (f-6) accounted for 67% of the 21 susceptible isolates (P
      < 0.003). A large proportion (>70%) of both MDR and susceptible E. coli BSI
      isolates represented community-onset infections. These observations show that
      factors other than the selective pressures of antimicrobial agents used in
      hospitals contribute to community-onset extraintestinal infections caused by
      clonal groups of E. coli regardless of their drug resistance.

PMID- 23147724
TI  - Both fidaxomicin and vancomycin inhibit outgrowth of Clostridium difficile
      spores.
AB  - Fidaxomicin (FDX) is approved to treat Clostridium difficile-associated diarrhea
      and is superior to vancomycin in providing a sustained clinical response (cure
      without recurrence in the subsequent 25 days). The mechanism(s) behind the low
      recurrence rate of FDX-treated patients could be multifactorial. Here, we tested
      effects of FDX, its metabolite OP-1118, and vancomycin on spore germination and
      determined that none affected the initiation of spore germination but all
      inhibited outgrowth of vegetative cells from germinated spores.

PMID- 23147725
TI  - Emergence of sequence type 779 methicillin-resistant Staphylococcus aureus
      harboring a novel pseudo staphylococcal cassette chromosome mec (SCCmec)-SCC
      SCCCRISPR composite element in Irish hospitals.
AB  - Methicillin-resistant Staphylococcus aureus (MRSA) has been a major cause of
      nosocomial infection in Irish hospitals for 4 decades, and replacement of
      predominant MRSA clones has occurred several times. An MRSA isolate recovered in
      2006 as part of a larger study of sporadic MRSA exhibited a rare spa (t878) and
      multilocus sequence (ST779) type and was nontypeable by PCR- and DNA microarray
      based staphylococcal cassette chromosome mec (SCCmec) element typing. Whole
      genome sequencing revealed the presence of a novel 51-kb composite island (CI)
      element with three distinct domains, each flanked by direct repeat and inverted
      repeat sequences, including (i) a pseudo SCCmec element (16.3 kb) carrying mecA
      with a novel mec class region, a fusidic acid resistance gene (fusC), and two
      copper resistance genes (copB and copC) but lacking ccr genes; (ii) an SCC
      element (17.5 kb) carrying a novel ccrAB4 allele; and (iii) an SCC element (17.4
      kb) carrying a novel ccrC allele and a clustered regularly interspaced short
      palindromic repeat (CRISPR) region. The novel CI was subsequently identified by
      PCR in an additional 13 t878/ST779 MRSA isolates, six from bloodstream
      infections, recovered between 2006 and 2011 in 11 hospitals. Analysis of open
      reading frames (ORFs) carried by the CI showed amino acid sequence similarity of
      44 to 100% to ORFs from S. aureus and coagulase-negative staphylococci (CoNS).
      These findings provide further evidence of genetic transfer between S. aureus and
      CoNS and show how this contributes to the emergence of novel SCCmec elements and
      MRSA strains. Ongoing surveillance of this MRSA strain is warranted and will
      require updating of currently used SCCmec typing methods.

PMID- 23147726
TI  - Population pharmacokinetics of fusidic acid: rationale for front-loaded dosing
      regimens due to autoinhibition of clearance.
AB  - The objectives of this analysis were to develop a population pharmacokinetic (PK)
      model to describe the absorption and disposition of fusidic acid after single and
      multiple doses and to determine the effect of food on the rate and extent of
      bioavailability. Plasma PK data from three phase 1 studies (n = 75; n = 14 with
      and without food) in which healthy subjects received sodium fusidate (500 to
      2,200 mg) as single or multiple oral doses every 8 h (q8h) or q12h for up to 7
      days were modeled using S-ADAPT (MCPEM algorithm). Accumulation of fusidic acid
      after multiple doses was more than that predicted based on single-dose data. The
      PK of fusidic acid was best described using a time-dependent mixed-order
      absorption process, two disposition compartments, and a turnover process to
      describe the autoinhibition of clearance. The mean total clearance (% coefficient
      of variation) was 1.28 liters/h (33%) and the maximum extent of autoinhibition
      was 71.0%, with a 50% inhibitory concentration (IC(50)) of 46.3 mg/liter (36%).
      Food decreased the extent of bioavailability by 18%. As a result of the
      autoinhibition of clearance, steady state can be achieved earlier with dosing
      regimens that contain higher doses (after 8 days for 750 mg q12h and 1 day for
      1,500 mg q12h on day 1 followed by 600 mg q12h versus 3 weeks for 500 mg q12h).
      Given that large initial doses autoinhibit the clearance of fusidic acid, this
      characteristic provides a basis for the administration of front-loaded dosing
      regimens of sodium fusidate which would allow for effective concentrations to be
      achieved early in therapy.

PMID- 23147727
TI  - Pharmacokinetic-pharmacodynamic modeling of unboosted Atazanavir in a cohort of
      stable HIV-infected patients.
AB  - Limited data on the pharmacokinetics and pharmacodynamics (PK/PD) of unboosted
      atazanavir (uATV) in treatment-experienced patients are available. The aim of
      this work was to study the PK/PD of unboosted atazanavir in a cohort of HIV
      infected patients. Data were available for 58 HIV-infected patients (69 uATV
      based regimens). Atazanavir concentrations were analyzed by using a population
      approach, and the relationship between atazanavir PK and clinical outcome was
      examined using logistic regression. The final PK model was a linear one
      compartment model with a mixture absorption model to account for two subgroups of
      absorbers. The mean (interindividual variability) of population PK parameters
      were as follows: clearance, 13.4 liters/h (40.7%), volume of distribution, 71.1
      liters (29.7%), and fraction of regular absorbers, 0.49. Seven subjects
      experienced virological failure after switch to uATV. All of them were identified
      as low absorbers in the PK modeling. The absorption rate constant (0.38 +/- 0.20
      versus 0.75 +/- 0.28 h(-1); P = 0.002) and ATV exposure (area under the
      concentration-time curve from 0 to 24 h [AUC(0-24)], 10.3 +/- 2.1 versus 22.4 +/-
      11.2 mg . h . liter(-1); P = 0.001) were significantly lower in patients with
      virological failure than in patients without failure. In the logistic regression
      analysis, both the absorption rate constant and ATV trough concentration
      significantly influenced the probability of virological failure. A significant
      relationship between ATV pharmacokinetics and virological response was observed
      in a cohort of HIV patients who were administered unboosted atazanavir. This
      study also suggests that twice-daily administration of uATV may optimize drug
      therapy.

PMID- 23147728
TI  - First detection of oqxAB in Salmonella spp. isolated from food.
AB  - Food-borne salmonellosis is an important public health problem worldwide and the
      second leading cause of food-borne illnesses in Hong Kong. In this study, the
      prevalence and antimicrobial resistance of Salmonella in meat products in Hong
      Kong were determined. Interestingly, a plasmid-mediated quinolone resistance
      (PMQR) gene combination, oqxAB, which mediates resistance to nalidixic acid,
      chloramphenicol, and olaquindox, was for the first time detectable on the
      chromosomes of two Salmonella enterica serovar Derby isolates. Further
      surveillance of oqxAB in Salmonella will be needed.

PMID- 23147729
TI  - Coordinate hyperproduction of SmeZ and SmeJK efflux pumps extends drug resistance
      in Stenotrophomonas maltophilia.
AB  - A Stenotrophomonas maltophilia mutant that coordinately hyper-expresses three
      resistance nodulation division-type efflux pump genes, smeZ, smeJ, and smeK, has
      been identified. SmeZ is responsible for elevating aminoglycoside MICs; SmeJ and
      SmeK are jointly responsible for elevating tetracycline, minocycline, and
      ciprofloxacin MICs and conferring levofloxacin resistance. One clinical isolate
      with this same phenotype was identified from a sample of six, and the isolate
      also coordinately hyper-expresses smeZ and smeJK, confirming the clinical
      relevance of our findings.

PMID- 23147730
TI  - Azole susceptibility and transcriptome profiling in Candida albicans
      mitochondrial electron transport chain complex I mutants.
AB  - Mitochondrial dysfunction in pathogenic fungi or model yeast causes altered
      susceptibilities to antifungal drugs. Here we have characterized the role of
      mitochondrial complex I (CI) of Candida albicans in antifungal susceptibility.
      Inhibitors of CI to CV, except for CII, increased the susceptibility of both
      patient and lab isolates, even those with a resistance phenotype. In addition, in
      a C. albicans library of 12 CI null mutants, 10 displayed hypersusceptibility to
      fluconazole and were severely growth inhibited on glycerol, implying a role for
      each gene in cell respiration. We chose two other hypersusceptible null mutants
      of C. albicans, the goa1Delta and ndh51Delta mutants, for transcriptional
      profiling by RNA-Seq. Goa1p is required for CI activity, while Ndh51p is a CI
      subunit. RNA-Seq revealed that both the ndh51Delta mutant and especially the
      goa1Delta mutant had significant downregulation of transporter genes, including
      CDR1 and CDR2, which encode efflux proteins. In the goa1Delta mutant, we noted
      the downregulation of genes required for the biogenesis and replication of
      peroxisomes, as well as metabolic pathways assigned to peroxisomes such as beta
      oxidation of fatty acids, glyoxylate bypass, and acetyl coenzyme A (acetyl-CoA)
      transferases that are known to shuttle acetyl-CoA between peroxisomes and
      mitochondria. The transcriptome profile of the ndh51Delta mutant did not include
      downregulation of peroxisome genes but had, instead, extensive downregulation of
      the ergosterol synthesis gene family. Our data establish that cell energy is
      required for azole susceptibility and that downregulation of efflux genes may be
      an outcome of that dysfunction. However, there are mutant-specific changes that
      may also increase the susceptibility of both of these C. albicans mutants to
      azoles.

PMID- 23147731
TI  - Thymidine analogues suppress autophagy and adipogenesis in cultured adipocytes.
AB  - Lipoatrophy in HIV patients can result from prolonged exposure to thymidine
      analogues. Mitochondrial toxicity leading to dysregulated adipogenesis and
      increased cell death has been proposed as a leading factor in the etiology of
      peripheral fat loss. We hypothesized that thymidine analogues interfere with
      autophagy, a lysosomal degradation pathway, which is important for mitochondrial
      quality control, cellular survival, and adipogenesis. We assessed the effects of
      zidovudine (AZT), stavudine (d4T), and lamivudine (3TC) on autophagy in
      eukaryotic cells and adipocytes (3T3-F442A) by fluorescence microscopy and flow
      cytometry. The effects were compared to interventions with established genetic
      and pharmacological inhibitors of autophagy and correlated to assessments of cell
      viability, proliferation, and differentiation. AZT and d4T, but not 3TC,
      inhibited both constitutive and induced autophagic activity in adipocytes. This
      inhibition was associated with accumulation of dysfunctional mitochondria,
      increased reactive oxygen species (ROS) production, increased apoptosis,
      decreased proliferation, and impaired adipogenic conversion. Autophagy inhibition
      was dose and time dependent and detectable at therapeutic drug concentrations.
      Similar phenotypic changes were obtained when genetic or pharmacological
      inhibition of autophagy was employed. Our data suggest that thymidine analogues
      disturb adipocyte function through inhibition of autophagy. This novel mechanism
      potentially contributes to peripheral fat loss in HIV-infected patients.

PMID- 23147732
TI  - Effects of obesity and sex on antimicrobial pharmacokinetics and acute kidney
      injury: validation of a preclinical model.
AB  - Obese patients may be at a greater risk for acute kidney injury (AKI) with the
      use of certain antimicrobial agents that are dosed by weight. Current preclinical
      models of AKI utilize the male rat within a narrow weight range that limits
      extrapolation of the generated results. We evaluated the pharmacokinetics and AKI
      potential of gentamicin in 14-week-old diet-induced obesity-prone (n = 40) and
      obesity-resistant (n = 40) rats of both sexes. Single daily doses of gentamicin
      (12.5, 18.75, or 25 mg/kg of body weight) or saline (control) were administered
      intraperitoneally for 14 doses. Blood samples were collected after doses 1, 7,
      and 14, assayed by liquid chromatography-tandem mass spectrometry (LC-MS/MS), and
      analyzed using a nonparametric population pharmacokinetic approach for
      gentamicin. Urine was collected after doses 1, 3, and 5 and assayed for kidney
      injury molecule 1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL)
      and normalized to creatinine (Cr) values. Histology was performed on all animals,
      and the degree of proximal tubular injury was graded. The mean (minimum, maximum)
      weight of the rats was 330 (136, 580) g. NGAL/Cr predicted AKI better than did
      KIM-1/Cr and was detectable in male rats after dose 1 and in obesity-prone female
      rats after dose 5. Proximal tubular injury by histology was significantly higher
      in male than in female rats. A significant relationship between the gentamicin
      area under the curve from zero to 24 hours (AUC(0-24)) estimates and the maximum
      NGAL/Cr ratio was observed. This preclinical model has the potential to aid with
      dose extrapolation for body size and improve assessment of the toxicology
      potential of antimicrobials in development.

PMID- 23147733
TI  - Colistin methanesulfonate and colistin pharmacokinetics in critically ill
      patients receiving continuous venovenous hemodiafiltration.
AB  - This report describes the pharmacokinetics of colistin methanesulfonate (CMS) and
      colistin in five intensive care unit patients receiving continuous venovenous
      hemodiafiltration. For CMS, the mean maximum concentration of drug in plasma
      (C(max)) after the fourth dose was 6.92 mg/liter and total clearance (CL) 8.23
      liters/h. For colistin, the mean concentration was 0.92 mg/liter and
      CL/metabolized fraction (f(m)) 18.91 liters/h. Colistin concentrations were below
      the current MIC breakpoints, and the area under the concentration-time curve for
      the free, unbound fraction of the drug over 24 h in the steady state divided by
      the MIC (fAUC/MIC) was lower than recommended, suggesting that a dosage regimen
      of 160 mg CMS every 8 h (q8h) is inadequate.

PMID- 23147734
TI  - A rationally engineered anti-HIV peptide fusion inhibitor with greatly reduced
      immunogenicity.
AB  - Peptides derived from the C-terminal heptad repeat 2 (HR2) region of the HIV-1
      gp41 envelope glycoprotein, so-called C peptides, are very efficient HIV-1 fusion
      inhibitors. We previously developed innovative gene therapeutic approaches aiming
      at the direct in vivo production of C peptides from genetically modified host
      cells and found that T cells expressing membrane-anchored or secreted C peptides
      are protected from HIV-1 infection. However, an unwanted immune response against
      such antiviral peptides may significantly impair clinical efficacy and pose
      safety risks to patients. To overcome this problem, we engineered a novel C
      peptide, V2o, with greatly reduced immunogenicity and excellent antiviral
      activity. V2o is based on the chimeric C peptide C46-EHO, which is derived from
      the HR2 regions of HIV-2(EHO) and HIV-1(HxB2) and has broad anti-HIV and anti
      simian immunodeficiency virus activity. Antibody and major histocompatibility
      complex class I epitopes within the C46-EHO peptide sequence were identified by
      in silico and in vitro analyses. Using rational design, we removed these epitopes
      by amino acid substitutions and thus minimized antigenicity and immunogenicity
      considerably. At the same time, the antiviral activity of the deimmunized peptide
      V2o was preserved or even enhanced compared to that of the parental C46-EHO
      peptide. Thus, V2o is an ideal candidate, especially for those novel therapeutic
      approaches for HIV infection that involve direct in vivo production of antiviral
      C peptides.

PMID- 23147735
TI  - Novel carbapenem antibiotics for parenteral and oral applications: in vitro and
      in vivo activities of 2-aryl carbapenems and their pharmacokinetics in laboratory
      animals.
AB  - SM-295291 and SM-369926 are new parenteral 2-aryl carbapenems with strong
      activity against major causative pathogens of community-acquired infections such
      as methicillin-susceptible Staphylococcus aureus, Streptococcus pneumoniae
      (including penicillin-resistant strains), Streptococcus pyogenes, Enterococcus
      faecalis, Klebsiella pneumoniae, Moraxella catarrhalis, Haemophilus influenzae
      (including beta-lactamase-negative ampicillin-resistant strains), and Neisseria
      gonorrhoeae (including ciprofloxacin-resistant strains), with MIC(90)s of <= 1
      MUg/ml. Unlike tebipenem (MIC(50), 8 MUg/ml), SM-295291 and SM-369926 had no
      activity against hospital pathogens such as Pseudomonas aeruginosa (MIC(50), >=
      128 MUg/ml). The bactericidal activities of SM-295291 and SM-369926 against
      penicillin-resistant S. pneumoniae and beta-lactamase-negative ampicillin
      resistant H. influenzae were equal or superior to that of tebipenem and greater
      than that of cefditoren. The therapeutic efficacies of intravenous
      administrations of SM-295291 and SM-369926 against experimentally induced
      infections in mice caused by penicillin-resistant S. pneumoniae and beta
      lactamase-negative ampicillin-resistant H. influenzae were equal or superior to
      that of tebipenem and greater than that of cefditoren, respectively, reflecting
      their in vitro activities. SM-295291 and SM-369926 showed intravenous
      pharmacokinetics similar to those of meropenem in terms of half-life in monkeys
      (0.4 h) and were stable against human dehydropeptidase I. SM-368589 and SM
      375769, which are medoxomil esters of SM-295291 and SM-369926, respectively,
      showed good oral bioavailability in rats, dogs, and monkeys (4.2 to 62.3%). Thus,
      2-aryl carbapenems are promising candidates that show an ideal broad spectrum for
      the treatment of community-acquired infections, including infections caused by
      penicillin-resistant S. pneumoniae and beta-lactamase-negative ampicillin
      resistant H. influenzae, have low selective pressure on antipseudomonal
      carbapenem-resistant nosocomial pathogens, and allow parenteral, oral, and switch
      therapies.

PMID- 23147736
TI  - A simple high-performance liquid chromatography method for simultaneous
      determination of three triazole antifungals in human plasma.
AB  - A rapid and simple high-performance liquid chromatography (HPLC) assay was
      developed for the simultaneous determination of three triazole antifungals
      (voriconazole, posaconazole, and itraconazole and the metabolite of itraconazole,
      hydroxyitraconazole) in human plasma. Sample preparation involved a simple one
      step protein precipitation with 1.0 M perchloric acid and methanol. After
      centrifugation, the supernatant was injected directly into the HPLC system.
      Voriconazole, posaconazole, itraconazole, its metabolite hydroxyitraconazole, and
      the internal standard naproxen were resolved on a C(6)-phenyl column using
      gradient elution of 0.01 M phosphate buffer, pH 3.5, and acetonitrile and
      detected with UV detection at 262 nm. Standard curves were linear over the
      concentration range of 0.05 to 10 mg/liter (r(2) > 0.99). Bias was <8.0% from
      0.05 to 10 mg/liter, intra- and interday coefficients of variation (imprecision)
      were <10%, and the limit of quantification was 0.05 mg/liter.

PMID- 23147737
TI  - Emergence and spread of plasmid-borne tet(B)::ISCR2 in minocycline-resistant
      Acinetobacter baumannii isolates.
AB  - Resistance to minocycline has emerged in multidrug-resistant Acinetobacter
      baumannii isolates from Buenos Aires hospitals. Few reports about the description
      and dispersion of tet genes in this species have been published. We observed the
      presence of tet(B) in all minocycline-resistant isolates. This gene was found to
      be associated with the ISCR2 mobile element, which may, in part, explain its
      dispersion.

PMID- 23147738
TI  - Mupirocin and chlorhexidine resistance in Staphylococcus aureus in patients with
      community-onset skin and soft tissue infections.
AB  - Decolonization measures, including mupirocin and chlorhexidine, are often
      prescribed to prevent Staphylococcus aureus skin and soft tissue infections
      (SSTI). The objective of this study was to determine the prevalence of high-level
      mupirocin and chlorhexidine resistance in S. aureus strains recovered from
      patients with SSTI before and after mupirocin and chlorhexidine administration
      and to determine whether carriage of a mupirocin- or chlorhexidine-resistant
      strain at baseline precluded S. aureus eradication. We recruited 1,089 patients
      with community-onset SSTI with or without S. aureus colonization. In addition to
      routine care, 483 patients were enrolled in a decolonization trial: 408 received
      intranasal mupirocin (with or without antimicrobial baths), and 258 performed
      chlorhexidine body washes. Patients were followed for up to 12 months with repeat
      colonization cultures. All S. aureus isolates were tested for high-level
      mupirocin and chlorhexidine resistance. At baseline, 23/1,089 (2.1%) patients
      carried a mupirocin-resistant S. aureus strain and 10/1,089 (0.9%) patients
      carried chlorhexidine-resistant S. aureus. Of 4 patients prescribed mupirocin,
      who carried a mupirocin-resistant S. aureus strain at baseline, 100% remained
      colonized at 1 month compared to 44% of the 324 patients without mupirocin
      resistance at baseline (P = 0.041). Of 2 patients prescribed chlorhexidine, who
      carried a chlorhexidine-resistant S. aureus strain at baseline, 50% remained
      colonized at 1 month compared to 48% of the 209 patients without chlorhexidine
      resistance at baseline (P = 1.0). The overall prevalence of mupirocin and
      chlorhexidine resistance is low in S. aureus isolates recovered from outpatients,
      but eradication efforts were less successful in patients carrying a mupirocin
      resistant S. aureus strain at baseline.

PMID- 23147739
TI  - Inhibition of Streptococcus pneumoniae penicillin-binding protein 2x and
      Actinomadura R39 DD-peptidase activities by ceftaroline.
AB  - Although the rate of acylation of a penicillin-resistant form of Streptococcus
      pneumoniae penicillin-binding protein 2x (PBP2x) by ceftaroline is 80-fold lower
      than that of its penicillin-sensitive counterpart, it remains sufficiently high
      (k(2)/K = 12,600 M(-1) s(-1)) to explain the sensitivity of the penicillin
      resistant strain to this new cephalosporin. Surprisingly, the Actinomadura R39 DD
      peptidase is not very sensitive to ceftaroline.

PMID- 23147740
TI  - Posaconazole pharmacodynamic target determination against wild-type and Cyp51
      mutant isolates of Aspergillus fumigatus in an in vivo model of invasive
      pulmonary aspergillosis.
AB  - Invasive pulmonary aspergillosis (IPA) is a devastating disease of
      immunocompromised patients. Pharmacodynamic (PD) examination of antifungal drug
      therapy in IPA is one strategy that may improve outcomes. The current study
      explored the PD target of posaconazole in an immunocompromised murine model of
      IPA against 10 A. fumigatus isolates, including 4 Cyp51 wild-type isolates and 6
      isolates carrying Cyp51 mutations conferring azole resistance. The posaconazole
      MIC range was 0.25 to 8 mg/liter. Following infection, mice were given 0.156 to
      160 mg/kg of body weight of oral posaconazole daily for 7 days. Efficacy was
      assessed by quantitative PCR (qPCR) of lung homogenate and survival. At the start
      of therapy, mice had 5.59 +/- 0.19 log(10) Aspergillus conidial equivalents
      (CE)/ml of lung homogenate, which increased to 7.11 +/- 0.29 log(10) CE/ml of
      lung homogenate in untreated animals. The infection was uniformly lethal prior to
      the study endpoint in control mice. A Hill-type dose response function was used
      to model the relationship between posaconazole free drug area under the
      concentration-time curve (AUC)/MIC and qPCR lung burden. The static dose range
      was 1.09 to 51.9 mg/kg/24 h. The free drug AUC/MIC PD target was 1.09 +/- 0.63
      for the group of strains. The 1-log kill free drug AUC/MIC was 2.07 +/- 1.02. The
      PD target was not significantly different for the wild-type and mutant organism
      groups. Mortality mirrored qPCR results, with the greatest improvement in
      survival noted at the same dosing regimens that produced static or cidal
      activity. Consideration of human pharmacokinetic data and the current static dose
      PD target would predict a clinical MIC threshold of 0.25 to 0.5 mg/liter.

PMID- 23147741
TI  - Efficacy of liposomal bismuth-ethanedithiol-loaded tobramycin after intratracheal
      administration in rats with pulmonary Pseudomonas aeruginosa infection.
AB  - We sought to investigate alterations in quorum-sensing signal molecule N-acyl
      homoserine lactone secretion and in the release of Pseudomonas aeruginosa
      virulence factors, as well as the in vivo antimicrobial activity of bismuth
      ethanedithiol incorporated into a liposome-loaded tobramycin formulation
      (LipoBiEDT-TOB) administered to rats chronically infected with P. aeruginosa. The
      quorum-sensing signal molecule N-acyl homoserine lactone was monitored by using a
      biosensor organism. P. aeruginosa virulence factors were assessed
      spectrophotometrically. An agar beads model of chronic Pseudomonas lung infection
      in rats was used to evaluate the efficacy of the liposomal formulation in the
      reduction of bacterial count. The levels of active tobramycin in the lungs and
      the kidneys were evaluated by microbiological assay. LipoBiEDT-TOB was effective
      in disrupting both quorum-sensing signal molecules N-3-oxo-dodeccanoylhomoserine
      lactone and N-butanoylhomoserine lactone, as well as significantly (P < 0.05)
      reducing lipase, chitinase, and protease production. At 24 h after 3 treatments,
      the CFU counts in lungs of animals treated with LipoBiEDT-TOB were of 3 log(10)
      CFU/lung, comparated to 7.4 and 4.7 log(10) CFU/lung, respectively, in untreated
      lungs and in lungs treated with free antibiotic. The antibiotic concentration
      after the last dose of LipoBiEDT-TOB was 25.1 MUg/lung, while no tobramycin was
      detected in the kidneys. As for the free antibiotic, we found 6.5 MUg/kidney but
      could not detect any tobramycin in the lungs. Taken together, LipoBiEDT-TOB
      reduced the production of quorum-sensing molecules and virulence factors and
      could highly improve the management of chronic pulmonary infection in cystic
      fibrosis patients.

PMID- 23147742
TI  - Vancomycin treatment's association with delayed intestinal tissue injury,
      clostridial overgrowth, and recurrence of Clostridium difficile infection in
      mice.
AB  - Antibiotic treatment, including vancomycin, for Clostridium difficile infection
      (CDI) has been associated with recurrence of disease in up to 25% of infected
      persons. This study investigated the effects of vancomycin on the clinical
      outcomes, intestinal histopathology, and anaerobic community during and after
      treatment in a murine model of CDI. C57BL/6 mice were challenged with C.
      difficile strain VPI 10463 after pretreatment with an antibiotic cocktail. Twenty
      four hours after infection, mice were treated daily with vancomycin,
      nitazoxanide, fidaxomicin, or metronidazaole for 5 days. Mice were monitored for
      either 6 or 12 days postinfection. Clinical, diarrhea, and histopathology scores
      were measured. Cecal contents or stool samples were assayed for clostridial or
      Bacteroides DNA and C. difficile toxins A and B. Vancomycin treatment of infected
      mice was associated with improved clinical, diarrhea, and histopathology scores
      and survival during treatment. However, after discontinuation of the drug,
      clinical scores and histopathology were worse in treated mice than in untreated
      infected controls. At the end of the study, 62% of the vancomycin-treated mice
      succumbed to recurrence, with an overall mortality rate equivalent to that of the
      untreated infected control group. Fidaxomicin-treated mice had outcomes similar
      to those of vancomycin-treated mice. C. difficile predominated over Bacteroides
      in cecal contents of vancomycin-treated mice, similar to findings for untreated
      infected mice. Decreasing the duration of vancomycin treatment from 5 days to 1
      day decreased recurrence and deaths. In conclusion, vancomycin improved clinical
      scores and histopathology acutely but was associated with poor outcome
      posttreatment in C. difficile-infected mice. Decreasing vancomycin exposure may
      decrease relapse and improve survival in CDI.

PMID- 23147744
TI  - Straightforward iron-catalyzed synthesis of vinylboronates by the hydroboration
      of alkynes.

PMID- 23147743
TI  - Case-control study of drug monitoring of beta-lactams in obese critically ill
      patients.
AB  - Severe sepsis and septic shock can alter the pharmacokinetics of broad-spectrum
      beta-lactams (meropenem, ceftazidime/cefepime, and piperacillin-tazobactam),
      resulting in inappropriate serum concentrations. Obesity may further modify the
      pharmacokinetics of these agents. We reviewed our data on critically ill obese
      patients (body mass index of >= 30 kg/m(2)) treated with a broad-spectrum beta
      lactam in whom therapeutic drug monitoring was performed and compared the data to
      those obtained in critically nonobese patients (body mass index of <25 kg/m(2))
      to assess whether there were differences in reaching optimal drug concentrations
      for the treatment of nosocomial infections. Sixty-eight serum levels were
      obtained from 49 obese patients. There was considerable variability in beta
      lactam serum concentrations (coefficient of variation of 50% to 92% for the three
      drugs). Standard drug regimens of beta-lactams resulted in insufficient serum
      concentrations in 32% of the patients and overdosed concentrations in 25%.
      Continuous renal replacement therapy was identified by multivariable analysis as
      a risk factor for overdosage and a protective factor for insufficient beta-lactam
      serum concentrations. The serum drug levels from the obese cohort were well
      matched for age, gender, renal function, and sequential organ failure assessment
      (SOFA) score to 68 serum levels measured in 59 nonobese patients. The only
      difference observed between the two cohorts was in the subgroup of patients
      treated with meropenem and who were not receiving continuous renal replacement
      therapy: serum concentrations were lower in the obese cohort. No differences were
      observed in pharmacokinetic variables between the two groups. Routine therapeutic
      drug monitoring of beta-lactams should be continued in obese critically ill
      patients.

PMID- 23147745
TI  - Mental disorders associated with driving under the influence of alcohol and/or
      drugs: a register-based study.
AB  - BACKGROUND/AIMS: Mental disorders are associated with driving under the influence
      (DUI), but the evidence is scarce and mostly focused on a limited group of repeat
      drunken drivers. Thus, the aim of this study was to examine which mental
      disorders were risk factors for DUI of alcohol only (DUIA), of illicit drugs
      (DUID) or of alcohol and psychoactive prescription drugs (DUIAP), and whether and
      how the risk differs over time. METHODS: A register-based case-control study was
      conducted. Cases (n=44,188) suspected by the police of DUI during 1997-2007 and
      controls (n=45,148) were drawn from the general Finnish population. The official
      national register of hospital treatments was the data source for mental
      disorders. The effects of mental disorders on DUI were estimated using logistic
      regression analysis. RESULTS: Substance use disorders increased the risk of DUI
      overall. Childhood- and adolescence-onset disorders were a strong predictor of
      DUID, and bipolar and depressive disorders predicted DUIAP. The risk was highest
      soon after hospital admission with a psychiatric diagnosis, but it decreased over
      time. CONCLUSIONS: Actions to prevent DUI should be developed and implemented
      during the treatment of mental disorders.

PMID- 23147746
TI  - Glycated albumin, not hemoglobin A1c, predicts cardiovascular hospitalization and
      length of stay in diabetic patients on dialysis.
AB  - BACKGROUND: The utility of glycated hemoglobin (HbA1c) and glycated albumin (GA)
      in diabetic dialysis patients remains unknown. GA was previously associated with
      all-cause hospitalization and patient survival. Relationships between GA, HbA1c,
      and casual plasma glucose (PG) with cause-specific cardiovascular (CV) disease,
      infectious disease (ID), and vascular access- (VA) related hospitalization rates
      and length of stay (LOS) were assessed. METHODS: 444 prevalent diabetic dialysis
      patients had monthly PG, quarterly GA, and all HbA1c values recorded for 2.33
      years; hospitalizations within 17 and 30 days of testing were evaluated. Best
      fit, time-dependent Cox models were constructed in unadjusted, case-mix-adjusted
      (age, sex, race, BMI, diabetes duration, dialysis vintage), and case-mix- plus
      lab-adjusted (hemoglobin, albumin, phosphorus) models. RESULTS: Mean +/- SD
      diabetes duration was 18.5 +/- 10.8 years and dialysis vintage 2.9 +/- 2.6 years.
      In fully adjusted models, CV hospitalization rates were associated with
      increasing GA (HR 1.32; 95% CI 1.11-1.57; p = 0.002 at 17 days; HR 1.21; p = 0.02
      at 30 days) and PG (HR 1.10; 95% CI 1.02-1.17; p = 0.01 at 17 days; HR 1.07; p =
      0.03 at 30 days), not HbA1c (HR 1.24; 95% CI 0.89-1.73; p = 0.21 at 17 days; HR
      1.26; p = 0.10 at 30 days). LOS for CV admissions was positively associated with
      GA (HR 1.18; 95% CI 1.01-1.39; p = 0.03), not PG (HR 1.04; 95% CI 0.99-1.10; p =
      0.15) or HbA1c (HR 1.03; 95% CI 0.92-1.15; p = 0.21). Admissions due to ID and VA
      complications (and LOS) did not correlate with these assays. CONCLUSIONS:
      Improved glycemic control based on GA and PG predicted CV-related
      hospitalizations; GA also predicted CV hospitalization LOS. HbA1c did not predict
      cause-specific hospitalizations in dialysis populations.

PMID- 23147747
TI  - First synthesis of (+)-myrrhanol C, an anti-prostate cancer lead.
AB  - The first synthesis of (+)-myrrhanol C (1), an antitumor polypodane-type bicyclic
      triterpene with inhibitory activity against androgen insensitive prostate
      cancers, is reported herein (IC(50) 10 MUmolar). A key step in our convergent
      synthesis of (+)-myrrhanol C and related analogues is the employment of a
      microbial stereo- and regioselective late stage C-H oxidation. A low-waste and
      sustainable process has been developed to prepare (+)-myrrhanol C for further
      biological studies.

PMID- 23147748
TI  - Accidental cannulation of the ascending lumbar vein during placement of an
      endovascular femoral venous cooling catheter.

PMID- 23147749
TI  - Massively calcified intravascular cast after removal of a tunneled central vein
      catheter for hemodialysis.
AB  - Vascular calcifications usually affect the arteries, while central vein
      calcifications are rare. A 45-year-old hemodialysis patient underwent a chest CT
      scan before central vein catheterization required for arteriovenous access
      thrombosis, in July 2011. He was on hemodialysis since 1995 and from 2005 on
      warfarin treatment because of repeated thrombosis and dysfunction of
      arteriovenous fistula and central vein catheters (CVC). A previous tunneled CVC
      placed in the left external jugular vein was removed in December 2010. Eight
      months later a chest CT scan showed a 79-mm irregular, linear, tubular radiopaque
      density in the superior vena cava and left brachiocephalic vein. The possibility
      of a retained catheter fragment was considered, but the final diagnosis was:
      calcified "cast" adherent to the vessel wall. This is the first report of an
      intravenous calcified "cast" (originating from peri-catheter calcification)
      retained after removal of a tunneled dialysis CVC. This finding is significant
      because it mimics a retained catheter fragment possibly leading to misdiagnosis
      and exposing patients to additional risk for unnecessary retrieving
      interventions. Catheter removal or over the wire substitution in the presence of
      a calcified cast could also be considered a risky procedure. Retained calcified
      cast should be included among the long-term complications of hemodialysis CVCs.
      At the time of publication, the patient is alive without any complication related
      to the pathology reported.

PMID- 23147750
TI  - Assessing causation of the extirpation of stream macroinvertebrates by a mixture
      of ions.
AB  - Increased ionic concentrations are associated with the impairment of benthic
      invertebrate assemblages. However, the causal nature of that relationship must be
      demonstrated so that it can be used to derive a benchmark for conductivity. The
      available evidence is organized in terms of six characteristics of causation: co
      occurrence, preceding causation, interaction, alteration, sufficiency, and time
      order. The inferential approach is to weight the lines of evidence using a
      consistent scoring system, weigh the evidence for each causal characteristic, and
      then assess the body of evidence. Through this assessment, the authors found that
      a mixture containing the ions Ca(+), Mg(+), HCO 3(-), and SO 4(-), as measured by
      conductivity, is a common cause of extirpation of aquatic macroinvertebrates in
      Appalachia where surface coal mining is prevalent. The mixture of ions is
      implicated as the cause rather than any individual constituent of the mixture.
      The authors also expect that ionic concentrations sufficient to cause
      extirpations would occur with a similar salt mixture containing predominately HCO
      3(-), SO 4(2-), Ca(2+), and Mg(2+) in other regions with naturally low
      conductivity. This case demonstrates the utility of the method for determining
      whether relationships identified in the field are causal.

PMID- 23147751
TI  - Virtual ligand-based screening reveals purmorphamine analogs with the capacity to
      induce the osteogenic differentiation of human mesenchymal stem cells.
AB  - Human mesenchymal stem cells (hMSCs) have extensive proliferative capacity, are
      able to self-renew and have the potential to differentiate into cells of the
      connective tissue lineages. These properties make them a putative cell type for
      tissue engineering applications, as well as a possible in vivo target for the
      pharmaceutical modulation of the differentiation processes. The aim of this study
      was to find one or more small-molecule substances that would enhance the
      osteogenic differentiation of hMSCs in vitro. The strategy used here was ligand
      based virtual screening for substances similar to the previously suggested
      osteoinductive purmorphamine followed by an in vitro screening of the selected
      analogs in hMSCs isolated from bone marrow. We investigated the osteoinductive
      capacity of several purmorphamine analogs by determining the protein and gene
      expression of markers for osteogenic differentiation as well as the extracellular
      matrix (ECM) mineralization of these cells. Treatment with two candidate
      substances or purmorphamine resulted in increased levels of alkaline phosphatase
      (ALP) activity compared to the control. Other purmorphamine analogs demonstrated
      higher calcium deposition in the ECM after 5 weeks of osteogenic differentiation,
      compared to both purmorphamine and the control condition. The resulting
      substances, which had positive effects on the osteogenic differentiation, are
      promising as possible modes of treatment for bone-related diseases or defects
      that target and enhance the osteogenic differentiation of MSCs, in vitro or in
      vivo. Furthermore, the concept of combining the virtual ligand-based screening
      method with in vitro screening, using human adult stem cells as a possible
      strategy for drug discovery, is demonstrated.

PMID- 23147753
TI  - Caring burden and associated factors of care providers for senile dementia
      patients in an urban-rural fringe of Fuzhou City, China.
AB  - BACKGROUND AND AIMS: Dementia is a serious disease that places undue burden on
      family care providers. This study aimed to investigate caring burden and
      associated factors of care providers for dementia patients in an urban-rural
      fringe area in China. METHODS: A total of 197 dementia patients >=65 years of age
      were identified from July-November 2007 in 22 villages of Gushan Town, Fuzhou
      City, China, and 152 care providers of the patients were recruited and analyzed.
      The Care Provider Burden Inventory was used to evaluate the main burdens
      including overall burden and time-dependent, developmental, physical, emotional
      and social burdens. Factors associating with caring burden were analyzed.
      RESULTS: The prevalence rate of dementia was 7.3% (197/2696) in study area. Four
      factors significantly increased overall care providers' burden score: daily hours
      of caring time, payment source for patients' medical expense, care providers'
      religion and care providers' role awareness (adjusted-R2 0.617). Patients with
      significantly impaired function of daily living (higher ADL scores) resulted in a
      higher caregivers' time-dependent burden. Increasing hour of caring per day
      increased care providers' time-dependent, physical and developmental burden. Care
      providers' view of their role awareness as obligation increased score of time
      dependent, developmental, physical and emotional burdens. Patient with physical
      disability significantly increased developmental, physical, emotional and social
      burdens. CONCLUSION: The main influence factors of the caring burden of care
      providers' for dementia patients were length of daily caring hours, source of
      care receivers' medical expenses, patient with physical disability and care
      providers' role awareness (i.e., obligated vs willing).

PMID- 23147752
TI  - K(+) , Na(+) , and Mg(2+)  on DNA translocation in silicon nitride nanopores.
AB  - In this work, we report on how salt concentration and cation species affect DNA
      translocation in voltage-biased silicon nitride nanopores. The translocation of
      dsDNA in linear, circular, and supercoiled forms was measured in salt solutions
      containing KCl, NaCl, and MgCl(2) . As the KCl concentrations were decreased from
      1 to 0.1 M, the time taken by a DNA molecule to pass through a nanopore was
      shorter and the frequency of the translocation in a folded configuration was
      reduced, suggesting an increase in DNA electrophoretic mobility and DNA
      persistence length. When the salt concentration was kept at 1 M, but replacing
      K(+)  with Na(+) , longer DNA translocation times (t(d) ) were observed. The
      addition of low concentrations of MgCl(2)  with 1.6 M KCl resulted in longer t(d)
      and an increased frequency of supercoiled DNA molecules in a branched form.
      These observations were consistent with the greater counterion charge screening
      ability of Na(+)  and Mg(2+)  as compared to K(+) . In addition, we demonstrated
      that dsDNA molecules indeed translocated through a ~10 nm nanopore by PCR
      amplification and gel electrophoresis. We also compared the dependence of DNA
      mobility and conformation on KCl concentration and cation species measured at
      single molecule level by silicon nitride nanopores with existing bulk-based
      experimental results and theoretical predictions.

PMID- 23147754
TI  - Anti-angiogenic activity of Herba Epimedii on zebrafish embryos in vivo and
      HUVECs in vitro.
AB  - Herba Epimedii, an herb commonly used in East Asian medicine, is commonly used
      for treatment of impotence, osteoporosis and many inflammatory conditions in
      traditional Chinese medicine. Recent studies revealed that Herba Epimedii also
      has anti-tumor or anti-cancer activities, which may possibly be mediated through
      anti-angiogenesis. This study aims to examine and confirm the anti-angiogenic
      activity in the herb using both in vivo and in vitro approaches. The 95% ethanol
      extract and four subsequent fractions (n-hexane, ethyl acetate (EA), n-butanol
      and aqueous fractions) of Herba Epimedii were tested on the zebrafish model by
      the quantitative assay for endogenous alkaline phosphatase; then, the active
      fraction was further tested on Tg(fli1a:EGFP)y1 zebrafish embryos and human
      umbilical vein endothelial cells (HUVECs) for the anti-angiogenic effects. In
      addition, the action mechanism of Herba Epimedii was further investigated on wild
      type zebrafish embryos and HUVECs. The EA fraction showed anti-angiogenic effects
      in both in vivo and in vitro models. Further experiments demonstrated that it
      might affect angiogenesis by acting on multiple molecular targets in zebrafish
      embryos and ERK signaling pathway in HUVECs. In conclusion, Herba Epimedii can
      inhibit angiogenesis, which may be the mechanism for its anti-inflammatory, anti
      tumor and anti-cancer actions.

PMID- 23147755
TI  - Entecavir and intermittent etanercept therapy in a patient with concurrent
      hepatitis B virus infection and psoriasis.

PMID- 23147757
TI  - Transplantation: An end to bone disease after renal transplantation?

PMID- 23147756
TI  - Kidney transplantation and the ageing immune system.
AB  - The world population is rapidly growing and ageing at a pace that is projected to
      continue for at least three decades. This shift towards an older populace has
      invariably increased the number of individuals with diseases related to ageing,
      such as chronic kidney disease. The increase in chronic kidney disease is
      associated with a growing number of elderly patients receiving kidney
      transplants. Understanding how the immune system changes with increasing age will
      help to define the risks of rejection and infection in the elderly population and
      will focus attention on the need for individualized immunosuppression for
      patients in this age group. This Review addresses what is currently known about
      ageing and the immune system, highlighting age-related changes that affect the
      outcome of transplantation in elderly individuals. The need for new strategies to
      improve outcomes in this growing population of elderly renal transplant
      recipients is also emphasized.

PMID- 23147760
TI  - Acute kidney injury: Adoptive transfer of tolerized dendritic cells--a potential
      new strategy for the prevention of AKI.

PMID- 23147758
TI  - Diagnosis and treatment of lupus nephritis flares--an update.
AB  - Relapses or flares of systemic lupus erythematosus (SLE) are frequent and
      observed in 27-66% of patients. SLE flares are defined as an increase in disease
      activity, in general, requiring alternative treatment or intensification of
      therapy. A renal flare is indicated by an increase in proteinuria and/or serum
      creatinine concentration, abnormal urine sediment or a reduction in creatinine
      clearance rate as a result of active disease. The morbidity associated with renal
      flares is derived from both the kidney damage due to lupus nephritis and
      treatment-related toxic effects. Current induction treatment protocols achieve
      remission in the majority of patients with lupus nephritis; however, few studies
      focus on treatment interventions for renal flares in these patients. The
      available data, however, suggest that remission can be induced again in a
      substantial percentage of patients experiencing a lupus nephritis flare. Lupus
      nephritis flares are independently associated with an increased risk of
      deterioration in renal function; prevention of renal flares might, therefore,
      also decrease long-term morbidity and mortality. Appropriate immunosuppressive
      maintenance therapy might lead to a decrease in the occurrence of renal and
      extrarenal flares in patients with SLE, and monitoring for the early detection
      and treatment of renal flares could improve their outcomes.

PMID- 23147761
TI  - Dialysis: Does daily haemodialysis reduce survival?

PMID- 23147764
TI  - Podocyte biology: a new regulator of podocytes.

PMID- 23147765
TI  - Acute kidney injury: Preoperative statin use is associated with a reduced risk of
      postoperative acute kidney injury.

PMID- 23147767
TI  - Acute kidney injury: Restriction of intravenous chloride intake may reduce the
      incidence of AKI in critically ill patients.

PMID- 23147768
TI  - Chronic kidney disease: Safe anticoagulation for patients with CKD--are we there
      yet?

PMID- 23147769
TI  - Periprocedural management and approach to bleeding in patients taking dabigatran.

PMID- 23147770
TI  - Percutaneous treatment of peripheral artery disease: novel techniques.

PMID- 23147771
TI  - Dual energy computed tomography demonstrated lung ventilation/perfusion mismatch
      in a 19-year-old patient with pulmonary embolism.

PMID- 23147773
TI  - Letter by Kuller and Mackey regarding article, "Lipids and lipoproteins and risk
      of different vascular events in the MRC/BHF Heart Protection study".

PMID- 23147774
TI  - Letter by Spiegel et al regarding article, "net clinical benefit of warfarin in
      patients with atrial fibrillation: a report from the Swedish atrial fibrillation
      cohort study".

PMID- 23147775
TI  - A new technique of endoprosthetic replacement for osteosarcoma of proximal femur
      with intra-articular extension.
AB  - INTRODUCTION: Osteosarcoma is the most common primary malignant tumour of bone
      and commonly involved sites are the distal femur, proximal tibia, and humerus.
      Osteosarcoma of proximal femur usually arises at the metaphysis and articular
      cartilage acts as a relative barrier to tumour spread, with extension into the
      hip joint being extremely rare. PRESENTATION OF CASE: A previously fit and well
      sixteen-year-old male presented with a 2month history of right hip pain and a
      limp. Plain radiographs and magnetic resonance imaging (MRI) showed an expansile
      lesion in the right femoral neck, extending 16cm distally from the proximal
      femoral articular surface through the intertrochanteric region into the upper
      right femoral shaft. There was also clear evidence of intra-articular extension
      into the acetabulum. DISCUSSION: Endoprosthetic replacement following resection
      is a good treatment option for proximal femoral tumours due to the low
      complication rate and achievement of good postoperative function. However,
      treatment of a proximal femoral lesion with intra-articular involvement by
      prosthetic reconstruction is challenging. We report a patient who presented with
      osteosarcoma of the proximal femur extending into the hip joint and describe the
      technique of en-bloc extra-articular resection of the acetabulum and proximal
      femur with reconstruction using a custom made prosthesis. CONCLUSION: We conclude
      that extra-articular resection and endoprosthetic reconstruction using a coned
      hemi-pelvic implant with fluted stem and a modular femoral implant is a useful
      treatment option in the management of a proximal femoral lesion involving the hip
      joint. It allows adequate tumour clearance and stable reconstruction for rapid
      post-operative recovery with early mobilisation.

PMID- 23147777
TI  - Edge-to-edge Alfieri technique for mitral valve repair:  which indications?
AB  - PURPOSE OF REVIEW: To outline the current indications to the edge-to-edge
      technique for mitral valve repair. Indeed, after its introduction in the early
      1990s, criteria for appropriate patient selection and technical issues of this
      approach have been progressively refined over the years and are now rather
      standardized. RECENT FINDINGS: The long-term results (up to 17 years) of this
      approach in the setting of degenerative mitral regurgitation with bileaflet and
      anterior leaflet prolapse have been recently reported and confirm the important
      role of this method in the surgical armamentarium of mitral valve reconstruction.
      In addition, recent data support the use of this method in new special situations
      and settings (systolic anterior motion prevention/treatment, congenital
      atrioventricular valve incompetence, as a 'rescue' procedure in case of
      suboptimal conventional repair). SUMMARY: In mitral regurgitation competence of
      the mitral valve can be restored by using a 'functional' rather than a
      conventional 'anatomical' repair. This 'functional' repair is realized by means
      of the edge-to-edge technique that consists in suturing together the facing
      portions of the anterior and posterior mitral valve leaflets in correspondence to
      the location of the regurgitant jet. The edge-to-edge technique was introduced in
      the early 1990s and has provided a useful contribution to the surgical
      armamentarium of mitral valve repair. Appropriate indications and awareness of
      the important technical aspects of the procedure are prerequisites for a good
      outcome. In this review the present role of the edge-to-edge repair, particularly
      in terms of indications and contraindications, will be outlined and discussed.

PMID- 23147776
TI  - Parathyroid adenoma associated with thymoma in a female adult with primary
      hyperparathyroidism.
AB  - INTRODUCTION: Parathyroid adenoma associated with a thymoma is a rare clinical
      entity and few cases have been reported in the literature. This association can
      be explained by the common embryologic origin of the parathyroid glands and the
      thymus. These patients may present only with clinical signs and symptoms of
      primary hyperparathyroidism making it difficult to suspect the coexistence of
      thymoma. PRESENTATION OF CASE: A 68-year-old female with medical history of
      primary hyperparathyroidism underwent surgical excision of a single parathyroid
      adenoma. Intra-operatively a small mass was detected in the proximity of the
      parathyroid adenoma and was also removed. Pathologic examination revealed
      parathyroid adenoma as suspected pre-operatively whereas the small mass excised
      was identified as a type A thymoma. The postoperative course of the patient was
      favourable, with normal serum calcium levels and in six months follow-up the
      patient is symptom-free and with no recurrence. DISCUSSION: Objective of this
      study is to report the rare case of a female adult with a parathyroid adenoma and
      a coexisting thymoma in order to underline the importance of these two
      pathologies and the ideal treatment that should be followed according to the
      latest records. CONCLUSION: Surgical removal of parathyroid adenoma is the
      treatment of choice for primary hyperparathyroidism, with complete recovery and
      no postoperative complications. Thymoma may be associated with primary
      hyperparathyoridism, with or without clinical signs and symptoms of myasthenia
      gravis and this is a rare clinical entity as very few cases have been described
      worldwide. To our knowledge this is the first case reported in Greece.

PMID- 23147778
TI  - Subcortical injury is an independent predictor of worsening neurological deficits
      following awake craniotomy procedures.
AB  - BACKGROUND: Tailored craniotomies for awake procedures limit cortical exposure.
      Recently we demonstrated that the identification of eloquent areas increased the
      risk of postoperative deficits. However, it was not clear whether the observed
      neurological deficits were caused by proximity of functional cortex to the tumor
      [cortical injury] or subcortical injury. OBJECTIVE: We hypothesize that
      subcortical injury during tumor resection is an important predictor of
      postoperative neurological deficits compared to cortical injury. METHODS: A
      retrospective review of 214 patients undergoing awake craniotomy was carried out
      in whom preoperative functional magnetic resonance imaging (fMRI) and cortical
      mapping (CM) were performed. A radiologist blinded to the clinical data reviewed
      and graded the postoperative changes on diffusion-weighted MR-imaging (DWI).
      RESULTS: Of the 40 cases who developed new intraoperative neurological deficit,
      36 (90%) occurred during subcortical dissection, 3 (7.5%) during both subcortical
      and cortical dissection, and 1 (2.5%) during cortical dissection. Neurological
      dysfunction acquired during subcortical dissection was an independent predictor
      of postoperative deficits both in the immediate postoperative period (P < .001)
      and at the 3-month follow-up (P < .001). Significant DWI restriction in the
      subcortical white matter was predictive of neurological deficits both immediately
      and at 3 months, P = .011 and P < .001, respectively. New or worsening deficits
      were seen in 38% of patients; however, at 3 months 13% had a mild persistent
      neurological deficit. CONCLUSION: Subcortical injury with significant DWI changes
      result in postoperative neurological decline despite our efforts to preserve
      cortical areas of function. This underscores the importance of preserving
      subcortical fiber tracts during awake craniotomy procedures.

PMID- 23147779
TI  - Differentiating diffuse World Health Organization grade II and IV astrocytomas
      with ex vivo magnetic resonance spectroscopy.
AB  - BACKGROUND: The prognosis and treatment of astrocytomas, which are primary brain
      tumors, vary depending on the grade of the tumor, necessitating a precise
      preoperative classification. Magnetic resonance spectroscopy (MRS) provides
      information about metabolites in tissues and is an emerging noninvasive tool to
      improve diagnostic accuracy in patients with intracranial neoplasia. OBJECTIVE:
      To investigate whether ex vivo MRS could differentiate World Health Organization
      grade II (A-II) and IV astrocytomas (glioblastomas; GBM) and to correlate MR
      spectral profiles with clinical parameters. METHODS: Patients with A-II and GBM
      (n = 58) scheduled for surgical resection were enrolled. Tumor specimens were
      collected during surgery and stored in liquid nitrogen before being analyzed with
      high-resolution magic angle spinning MRS. The tumors were histopathologically
      classified according to World Health Organization criteria as GBM (n = 48) and A
      II (n = 10). RESULTS: Multivariate analysis of ex vivo proton high-resolution
      magic angle spinning spectra MRS showed differences in the metabolic profiles of
      different grades of astrocytomas. A-II had higher levels of glycerophosphocholine
      and myo-inositol than GBM. The latter had more phosphocholine, glycine, and
      lipids. We observed a significant metabolic difference between recurrent and
      nonrecurrent GBM (P < .001). Primary GBM had more phosphocholine than recurrent
      GBM. A significant correlation (P < .001) between lipid and lactate signals and
      histologically estimated percentage of necrosis was observed in GBM. Spectral
      profiles were not correlated with age, survival, or magnetic resonance imaging
      defined tumor volume. CONCLUSION: Ex vivo MRS can differentiate astrocytomas
      based on their metabolic profiles.

PMID- 23147780
TI  - Beneficial effect of subsequent lesion procedures after nonresponse to initial
      cingulotomy for severe, treatment-refractory obsessive-compulsive disorder.
AB  - BACKGROUND: Anterior cingulotomy (AC) can be an effective therapy for patients
      with severe obsessive-compulsive disorder who are refractory to traditional
      medical therapy. For patients who do not respond to AC, the benefit of additional
      lesion procedures vs continued medical management remains unknown. OBJECTIVE: To
      determine whether a second lesion procedure is beneficial after unsuccessful
      initial AC. METHODS: In this retrospective cohort study, we reviewed the records
      of 31 patients who were nonresponders to initial AC. Full response was defined as
      at least a 35% decrease and partial response as a 25% to 34% decrease in Yale
      Brown Obsessive-Compulsive Scale scores. Yale-Brown Obsessive-Compulsive Scale
      change was compared between patients who underwent additional surgery and those
      treated nonsurgically. In addition, for patients who underwent additional
      surgery, we compared the benefit of subcaudate tractotomy with repeat AC
      (extension of the initial lesion) as the second procedure. RESULTS: Nineteen
      patients underwent a second surgery and 12 patients continued nonsurgical
      therapy. Fifty-three percent of patients who received additional surgery were
      full responders and 21% were partial responders at the most recent follow-up
      compared with 17% full responders and 25% partial responders among those who
      continued conventional therapy (P = .02). Of the patients who underwent an
      additional surgery, there were 64% full and 9% partial responders in the
      subcaudate tractotomy group compared with 38% full and 38% partial responders in
      the repeat AC group (P = .04). CONCLUSION: Second lesion surgery can be a safe
      and effective therapy for patients who do not respond to initial AC. Subcaudate
      tractotomy may confer a higher response rate than repeat cingulotomy.

PMID- 23147781
TI  - Deep brain stimulation of the lateral habenular complex in treatment-resistant
      depression: traps and pitfalls of trajectory choice.
AB  - BACKGROUND: Deep brain stimulation (DBS) has recently been discussed as a
      promising treatment option for severe cases of major depression. Experimental
      data have suggested that the lateral habenular complex (LHb-c) is a central
      region of depression-related neuronal circuits. Because of its location close to
      the midline, stereotactic targeting of the LHb-c presents surgeons with distinct
      challenges. OBJECTIVE: To define the obstacles of DBS surgery for stimulation of
      the LHb-c and thus to establish safe trajectories. METHODS: Stereotactic magnetic
      resonance imaging data sets of 54 hemispheres originating from 27 DBS patients
      were taken for analysis on a stereotactic planning workstation. After alignment
      of images according to the anterior commissure--posterior commissure definition,
      analyses focused on vessels and enlarged ventricles interfering with
      trajectories. RESULTS: As major trajectory obstacles, enlarged ventricles and an
      interfering superior thalamic vein were found. A standard frontal trajectory
      (angle > 40 degrees  relative to the anterior commissure--posterior commissure in
      sagittal images) for bilateral stimulation was safely applicable in 48% of
      patients, whereas a steeper frontal trajectory (angle <40 relative to the
      anterior commissure--posterior commissure in sagittal images) for bilateral
      stimulation was possible in 96%. Taken together, safe bilateral targeting of the
      LHb-c was possible in 98% of all patients. CONCLUSION: Targeting LHb-c is a
      feasible and safe technique in the majority of patients undergoing surgery for
      DBS. However, meticulous individual planning to avoid interference with
      ventricles and thalamus-related veins is mandatory because an alternative steep
      frontal entry point has to be considered in about half of the patients.

PMID- 23147782
TI  - Intraoperative visualization of residual tumor: the role of perfusion-weighted
      imaging in a high-field intraoperative magnetic resonance scanner.
AB  - BACKGROUND: High-field, intraoperative magnetic resonance imaging (iMRI) achieves
      free tumor margins in glioma surgery by involving anatomic neuronavigation and
      sophisticated functional imaging. OBJECTIVE: To evaluate the role of perfusion
      weighted iMRI as an aid to detect residual tumor and to guide its resection.
      METHODS: Twenty-two patients undergoing intraoperative scanning (in a dual-room
      1.5-T magnet setting) during the resection of high-grade gliomas were examined
      with perfusion-weighted iMRI. The generated relative cerebral blood volume (rCBV)
      maps were scrutinized for any hot spots indicative of tumor remnants, and region
      of-interest analysis was performed. Differences among the rCBV region-of-interest
      estimates in residual tumor, free tumor margins, and normal white matter were
      analyzed. Histopathology of the tissue specimens and the neurosurgeon's
      intraoperative macroscopic estimations were considered the reference standards.
      RESULTS: In all cases, diagnostic rCBV perfusion maps were generated.
      Interpretation of perfusion maps demonstrated that gross total resection of
      gliomas was achieved in 4 of 22 cases (18%), which was macroscopically and
      histopathologically verified, whereas in 18 of 22 cases (82%), the perfusion
      weighted iMRI revealed hot spots indicating subtotal tumor removal. The latter
      proved to be true in all but 1 case. The receiver-operating characteristic curves
      of the qualitative visual and quantitative analyses showed excellent sensitivity
      and specificity rates. Statistical analysis demonstrated statistically
      significant differences for the mean rCBV and maximum rCBV between residual
      disease and tumor-free margins (P = .002 for both). CONCLUSION: Perfusion
      weighted iMRI may be implemented easily into imaging protocols and may assist the
      surgeon in detecting residual tumor volume.

PMID- 23147783
TI  - Transfemoral transarterial onyx embolization of carotid body paragangliomas: 
      technical considerations, results, and strategies for complication avoidance.
AB  - BACKGROUND: The association of carotid body paragangliomas with neurovascular
      structures can cause cranial nerve injury and significant intraoperative blood
      loss. Preoperative embolization may be performed either percutaneously or
      transarterially. OBJECTIVE: We reviewed our experience with transfemoral
      transarterial Onyx embolization. METHODS: We retrospectively reviewed a
      prospectively maintained database of head and neck tumors embolized between
      November 2007 and February 2012. Patients were assessed for number of sessions of
      embolization, number of pedicles embolized, fluoroscopic time, extent of tumor
      devascularization as assessed by postembolization angiography, and operative
      blood loss. RESULTS: Eleven patients (5 men, 6 women; mean age, 48.1 years) with
      13 paragangliomas (5 right-sided, 9 left-sided, 2 bilateral) underwent
      preoperative embolization for 12 tumors. Onyx alone was used in 9 cases. In a
      mean of 1.2 embolization sessions (range, 1-2), an average of 2.8 pedicles
      (range, 1-7) was embolized. The average fluoroscopic time was 54.3 minutes. In 5
      cases, the tumors were completely devascularized by using this strategy. In 5
      cases, more than 90% tumor devascularization was achieved. In the remaining 2
      cases, tumor devascularization was more than 50%. A partial cranial nerve XII
      palsy was the only postprocedural complication. The mean surgical blood loss was
      191.7 mL (range, 25-600 mL). CONCLUSION: The arterial supply to carotid body
      tumors can be catheterized effectively through a transfemoral approach,
      permitting embolization of feeding pedicles. Transarterial Onyx embolization of
      these lesions is safe and effective, and it decreases blood loss during surgical
      resection.

PMID- 23147784
TI  - In reply.

PMID- 23147785
TI  - Hemangiopericytomas in the spine: clinical features, classification, treatment,
      and long-term follow-up in 26 patients.
AB  - BACKGROUND: Intraspinal hemangiopericytoma (HPC) is a rare and malignant extra
      axial tumor with a strong tendency to recur and metastasize. There is a paucity
      in the literature of large case series of patients with intraspinal HPCs.
      OBJECTIVE: We retrospectively analyzed the clinical radiological and histological
      features, classification, and treatment of 26 patients with HPCs in the spine.
      METHODS: Twenty-six patients with HPCs in the spine were treated at our
      institution between 1987 and 2010. Medical records were reviewed retrospectively
      to collect data on the clinical features, tumor morphology, surgical resection,
      recurrence, and follow-up. RESULTS: The 26 patients were predominantly male, and
      the mean age at diagnosis was 33.8 years. The intraspinal HPCs were divided into
      3 types and 5 subtypes. Most of them involved the neighboring segments and/or
      caused bony erosion. All tumors were immunohistochemically positive for vimentin
      and negative for epithelial membrane antigen. All patients underwent at least 1
      surgery, and most of them received postsurgical radiotherapy. The 5-year Kaplan
      Meier rate of survival was 76%. The 5-year recurrence-free rate of survival was
      29.4%. Only the tumor pathological grade was significantly associated with
      survival time and recurrence. CONCLUSION: High-grade tumors had a shorter
      survival time and recurred earlier than low-grade tumors. Surgical removal and
      postoperative radiotherapy are critical for the treatment of intraspinal HPCs.
      However, total resection may not necessary for these tumors. Stereotactic
      radiosurgery may be a good alternative to control the recurrent lesions.

PMID- 23147786
TI  - Cerebral aneurysms in pregnancy and delivery:  pregnancy and delivery do not
      increase the risk of aneurysm rupture.
AB  - BACKGROUND: It is not known what effect pregnancy or delivery has on the risk of
      rupture of an intracranial aneurysm, and, consequently, the optimal management of
      unruptured aneurysms in pregnancy is unclear. OBJECTIVE: To study the effect of
      pregnancy and delivery on the risk of rupture of intracranial aneurysms and to
      delineate trends in neurosurgical and obstetric management of pregnant women with
      intracranial aneurysms. METHODS: The Nationwide Inpatient Sample data were
      analyzed for years 1988 to 2009 to estimate the risk of aneurysm rupture during
      pregnancies and deliveries. We calculated the risk by dividing the observed
      number of patients with ruptured aneurysm during pregnancy and delivery by the
      expected number based on the incidence among women of pregnancy age. RESULTS:
      There were 714 and 172 hospitalizations involving ruptured aneurysms with
      pregnancy and delivery, respectively. Assuming 1.8% prevalence of unruptured
      aneurysms among all women of pregnancy age, we estimated that 48,873 women
      hospitalized for pregnancy and 312,128 women hospitalized for delivery had
      unruptured aneurysms. The risks of rupture during pregnancy and deliveries were
      1.4% (95% confidence interval [CI] = [1.35, 1.57]) and 0.05% (95% CI = [0.0468,
      0.0634]), respectively. Of 218 deliveries performed with unruptured aneurysm, 153
      were cesarean deliveries (70.18%, 95% CI = [64.06, 76.30%]), suggesting that the
      rate of cesarean deliveries in patients with unruptured aneurysms is
      significantly higher than in the general population (P < .001). CONCLUSION: We
      were not able to find an increased association between pregnancy or delivery and
      the risk of rupture of cerebral aneurysms. The significantly higher rate of
      cesarean deliveries performed in patients with unruptured aneurysms may not be
      necessary.

PMID- 23147787
TI  - Basilar tip aneurysms:  a microsurgical and endovascular contemporary series of
      100 patients.
AB  - BACKGROUND: Endovascular therapy has largely replaced microsurgical clipping for
      the treatment of basilar tip aneurysms. OBJECTIVE: We describe the variables our
      center evaluates when choosing to clip or coil basilar tip aneurysms and our
      outcomes. Four case illustrations are presented. METHODS: All patients with
      ruptured or unruptured basilar tip aneurysms from 2005 to April 2012 were
      examined. The patients were treated by 2 interventional neuroradiologists and 2
      dually trained neurosurgeons. RESULTS: There were 63 ruptured (clipped 38%,
      coiled 62%) and 37 unruptured (clipped 35%, coiled 65%) aneurysms in this 100
      patient study. Seventy percent of the patients with ruptured aneurysms and 92% of
      the patients with unruptured aneurysms had a good outcome (modified Rankin scale
      0-2) at 3 months. For ruptured aneurysms, there was a statistically significant
      difference in clipping and coiling with respect to age and treatment modality
      (clip 48.8 years, coil 57.6 years). Patients in the coiled group had higher dome
      to-neck (1.3 vs 1.1) (P = .01) and aspect ratios (1.6 vs 1.2) (P = .007). In the
      ruptured coiling group, 69.5% achieved a Raymond 1 radiographic outcome, 28%
      Raymond 2, and 2.5% Raymond 3. Eleven (17.4%) patients required re-treatment, and
      3 (4.4%) patients were re-treated more than twice. Coiling of unruptured
      aneurysms resulted in 75% Raymond 1. There were no residual lesions for
      unruptured clipped aneurysms. There were no differences in outcome between
      clipping and coiling in the ruptured and unruptured group. CONCLUSION: In our
      current management of basilar tip aneurysms, the majority can be treated via
      endovascular means, albeit with the expectation of a higher percentage of
      residual lesions and recurrences. Microsurgery is still appropriate for aneurysms
      with complex neck morphologies and in young patients desiring a more durable
      treatment.

PMID- 23147788
TI  - Intra-arterial injection fluorescein videoangiography in aneurysm surgery.
AB  - BACKGROUND: To visualize blood flow in the arteries and aneurysm during surgery,
      intravenous fluorescence videoangiography has been used. However, the image
      contrast with this procedure is diminished by repeated study because the dye
      remains for about 10 minutes after injection. OBJECTIVE: To determine the optimal
      dye concentration and to clarify the usefulness of fluorescein videoangiography
      by intra-arterial dye injection. METHODS: In the pilot study, fluorescein sodium
      dissolved at various concentrations was illuminated with excitation light, and
      fluorescence was detected by cameras. The fluorescence of 0.001% fluorescein
      sodium solution mixed with plasma at various concentrations was then examined. In
      13 aneurysm patients, dye solution was administered through the catheter for
      intraoperative digital subtraction angiography. The intravenous injection method
      was also performed, and the findings were compared. RESULTS: Dye was clinically
      used at a concentration of 0.005% to 0.1% on the basis of the results of the
      pilot study. Fluorescence emission from the vessels and aneurysms was clearly
      observed by both methods; however, arterial injection provided brighter emission,
      resulting in clearer demonstration of the bloodstream than venous injection. Dye
      clearance was also quicker, which allowed repeat injections without delay. Dye
      filling in the aneurysm indicating incomplete occlusion was detected in 2 cases,
      and occlusion of the perforating artery was observed in 2 cases. CONCLUSION:
      Intra-arterial fluorescein videoangiography provides brighter and clearer imaging
      of blood flow with a smaller dose of dye than intravenous videoangiography. It
      can be repeated within a short time and is useful for detecting incomplete
      clipping or unexpected obstruction of arteries.

PMID- 23147789
TI  - Crystal structure of a TALE protein reveals an extended N-terminal DNA binding
      region.

PMID- 23147790
TI  - Crystal structure of an LRR protein with two solenoids.

PMID- 23147791
TI  - Chronic lymphocytic leukemia: a tale of one or two signals?
AB  - The significant correlation between disease aggressiveness and the gene and
      protein structures of the B-cell receptors (BCRs) expressed on chronic
      lymphocytic leukemia (CLL) cells, together with the evidence for chronic
      activation of the BCR pathway, have led to the hypothesis that this leukemia
      initiates and progresses by selecting normal B lymphocytes reactive with a
      restricted set of (auto)antigens. A study recently published in Nature identified
      a novel signal-initiating interaction between the third complementary determining
      region of the IG heavy chain variable domain (HCDR3) and an epitope in the second
      framework region (FR2) that appears to be unique to CLL B cells and that calls
      into question the need for classical antigen binding in the activation and
      expansion of the leukemic cells. These findings are discussed in the context of
      available information about the antigen reactivity of CLL B cells and its
      potential role in clonal survival and drive.

PMID- 23147792
TI  - Overcoming the chromatin barrier to end resection.
AB  - Repair of double-strand breaks by homologous recombination requires Repair of
      double-strand breaks by homologous recombination requires 5'-3' resection of the
      DNA ends to create 3' single-stranded DNA tails. While much progress has been
      made in identifying the proteins that directly participate in end resection, how
      this process occurs in the context of chromatin is not well understood. Two
      papers in Nature report that Fun30, a poorly characterized member of the
      Swi2/Snf2 family of chromatin remodelers, plays a role in end processing by
      facilitating the Exo1 and Sgs1-Dna2 resection pathways.

PMID- 23147793
TI  - The conformational shifts of the voltage sensing domains between Na(v)Rh and
      Na(v)Ab.

PMID- 23147795
TI  - Evidence for GAL3ST4 mutation as the potential cause of pectus excavatum.

PMID- 23147794
TI  - Defective FGF signaling causes coloboma formation and disrupts retinal
      neurogenesis.
AB  - The optic fissure (OF) is a transient opening on the ventral side of the
      developing vertebrate eye that closes before nearly all retinal progenitor cell
      differentiation has occurred. Failure to close the OF results in coloboma, a
      congenital disease that is a major cause of childhood blindness. Although human
      genetic studies and animal models have linked a number of genes to coloboma, the
      cellular and molecular mechanisms driving the closure of the OF are still largely
      unclear. In this study, we used Cre-LoxP-mediated conditional removal of
      fibroblast growth factor (FGF) receptors, Fgfr1 and Fgfr2, from the developing
      optic cup (OC) to show that FGF signaling regulates the closing of the OF. Our
      molecular, cellular and transcriptome analyses of Fgfr1 and Fgfr2 double
      conditional knockout OCs suggest that FGF signaling controls the OF closure
      through modulation of retinal progenitor cell proliferation, fate specification
      and morphological changes. Furthermore, Fgfr1 and Fgfr2 double conditional mutant
      retinal progenitor cells fail to initiate retinal ganglion cell (RGC) genesis.
      Taken together, our mouse genetic studies reveal that FGF signaling is essential
      for OF morphogenesis and RGC development.

PMID- 23147796
TI  - The novel quantitative trait locus GL3.1 controls rice grain size and yield by
      regulating Cyclin-T1;3.
AB  - Increased crop yields are required to support rapid population growth worldwide.
      Grain weight is a key component of rice yield, but the underlying molecular
      mechanisms that control it remain elusive. Here, we report the cloning and
      characterization of a new quantitative trait locus (QTL) for the control of rice
      grain length, weight and yield. This locus, GL3.1, encodes a protein phosphatase
      kelch (PPKL) family - Ser/Thr phosphatase. GL3.1 is a member of the large grain
      WY3 variety, which is associated with weaker dephosphorylation activity than the
      small grain FAZ1 variety. GL3.1-WY3 influences protein phosphorylation in the
      spikelet to accelerate cell division, thereby resulting in longer grains and
      higher yields. Further studies have shown that GL3.1 directly dephosphorylates
      its substrate, Cyclin-T1;3, which has only been rarely studied in plants. The
      downregulation of Cyclin-T1;3 in rice resulted in a shorter grain, which
      indicates a novel function for Cyclin-T in cell cycle regulation. Our findings
      suggest a new mechanism for the regulation of grain size and yield that is driven
      through a novel phosphatase-mediated process that affects the phosphorylation of
      Cyclin-T1;3 during cell cycle progression, and thus provide new insight into the
      mechanisms underlying crop seed development. We bred a new variety containing the
      natural GL3.1 allele that demonstrated increased grain yield, which indicates
      that GL3.1 is a powerful tool for breeding high-yield crops.

PMID- 23147798
TI  - Non-coding transcription SETs up regulation.
AB  - An abundance of long non-coding RNA (lncRNA) present in most species from yeast
      to human are involved in transcriptional regulation, dosage compensation and
      imprinting. This underscores the importance of lncRNA as functional RNA despite
      the fact that they do not produce proteins. Two recent papers in Cell have
      demonstrated that transcription of the non-conserved lncRNAs, but not the RNAs
      themselves, is necessary to introduce co-transcriptional regulatory histone marks
      to regulate gene expression.

PMID- 23147797
TI  - Zscan4 promotes genomic stability during reprogramming and dramatically improves
      the quality of iPS cells as demonstrated by tetraploid complementation.
AB  - Induced pluripotent stem (iPS) cells generated using Yamanaka factors have great
      potential for use in autologous cell therapy. However, genomic abnormalities
      exist in human iPS cells, and most mouse iPS cells are not fully pluripotent, as
      evaluated by the tetraploid complementation assay (TCA); this is most likely
      associated with the DNA damage response (DDR) occurred in early reprogramming
      induced by Yamanaka factors. In contrast, nuclear transfer can faithfully
      reprogram somatic cells into embryonic stem (ES) cells that satisfy the TCA. We
      thus hypothesized that factors involved in oocyte-induced reprogramming may
      stabilize the somatic genome during reprogramming, and improve the quality of the
      resultant iPS cells. To test this hypothesis, we screened for factors that could
      decrease DDR signals during iPS cell induction. We determined that Zscan4, in
      combination with the Yamanaka factors, not only remarkably reduced the DDR but
      also markedly promoted the efficiency of iPS cell generation. The inclusion of
      Zscan4 stabilized the genomic DNA, resulting in p53 downregulation. Furthermore,
      Zscan4 also enhanced telomere lengthening as early as 3 days post-infection
      through a telomere recombination-based mechanism. As a result, iPS cells
      generated with addition of Zscan4 exhibited longer telomeres than classical iPS
      cells. Strikingly, more than 50% of iPS cell lines (11/19) produced via this
      "Zscan4 protocol" gave rise to live-borne all-iPS cell mice as determined by TCA,
      compared to 1/12 for lines produced using the classical Yamanaka factors. Our
      findings provide the first demonstration that maintaining genomic stability
      during reprogramming promotes the generation of high quality iPS cells.

PMID- 23147799
TI  - Microchannel-induced change of chemical wave propagation dynamics: importance of
      ratio between the inlet and the channel sizes.
AB  - The ability to control chemical wave propagation dynamics could stimulate the
      science and technology of artificial and biological spatiotemporal oscillating
      phenomena. In contrast to the conventional chemical approaches to control the
      wave front dynamics, here we report a physical approach to tune the propagation
      dynamics under the same chemical conditions. By using well-designed microchannels
      with different channel widths and depths, the propagation velocity was
      successfully controlled based on two independent effects: (i) a transition in the
      proton diffusion mode and (ii) the formation of a slanted wave front. Numerical
      analysis yielded a simple relationship between the propagation velocity and the
      microchannel configuration, which offers a simple and general way of controlling
      chemical wave propagation.

PMID- 23147800
TI  - Investigation and enhancement of the stability and performance of water reduction
      systems based on cyclometalated iridium(III) complexes.
AB  - Water reduction systems that use a bis-cyclometalated Ir(III) photosensitiser
      (PS) along with homogeneous Pd complexes as a source of in-situ-formed colloidal
      Pd as the water reducing complex (WRC) and triethylamine (TEA) as the sacrificial
      electron donor were tested and characterised with respect to their photocatalytic
      H(2) production performance. It was confirmed that substitution of the 2-(pyridin
      2-yl)benzen-1-ide (pyb) ligand in the well-known system [Ir(pyb)(2)(bpy)](+)
      (bpy=2,2'-bipyridine) by the fluorinated cyclometalating ligand 5-fluoro-2-(5
      methylpyridin-2-yl)benzen-1-ide (Fmpyb) tremendously enhanced the H(2) production
      rate. Moreover, variation of the bidentate N^N ligand bpy by alkyl substitution
      in the 4,4'-position resulted in an increase in the H(2) production yield by a
      factor of three. The incident-photon-to-hydrogen-efficiency could be enhanced
      from 2.6 to 12.3%. Furthermore, a new dinuclear Co complex was used as a
      reduction catalyst and showed up to 760 turnovers after 20 h. A detailed study of
      the concentration impact of all components in the photoredox system was
      performed. DFT calculations were used to aid the explanation of the findings.

PMID- 23147801
TI  - DNA cohesion through bubble-bubble recognition.
AB  - This communication reports a novel intermolecular interaction for structural DNA
      nanotechnology.

PMID- 23147802
TI  - Supplementation with oat protein ameliorates exercise-induced fatigue in mice.
AB  - Oat protein was purified from oat meal and its effects on swimming performance
      and related biochemical parameters were investigated. Thirty male Kun-ming mice
      were divided into the normal control, the oat meal and the oat protein group (n =
      10). They were fed with a laboratory food for 30 days, then were subjected to
      swim to exhaustion. Their swimming endurance and the major metabolic substrates
      were measured from serum, liver and muscle. The results showed that no
      significant differences were observed in swimming endurance test between the
      normal control group and the oat protein group (P > 0.05). Mice in the oat meal
      group had significantly longer swimming endurance compared to the normal control
      group (P < 0.05). Furthermore, dietary oat protein increased the levels of liver
      glycogen, enhanced the activities of lactic dehydrogenase and superoxide
      dismutase, and decreased the levels of blood urea nitrogen and malondialdehyde in
      serum. These results suggested that oat protein was effective in improving the
      physiological condition of the mice.

PMID- 23147803
TI  - Elucidating the behavior of physical fatigue and mental fatigue in cancer
      patients: a review of the literature.
AB  - BACKGROUND: Although the multidimensional nature of cancer-related fatigue is
      widely accepted, it could be questioned whether fatigue dimensions are
      expressions of one symptom (multidimensional concept) or expressions of several
      phenomena that are all called fatigue but actually are separate symptoms
      (multiple-symptom concept). METHODS: Therefore, we investigated in this review
      whether physical fatigue and mental fatigue behave differently in cancer patients
      by studying their intensity in different stages of cancer, their changes in
      intensity during anti-tumor therapy, the variables to which they are related, and
      their changes in intensity by interventions on fatigue. RESULTS: In some studies,
      physical fatigue and mental fatigue behaved similarly: they were both more
      intense in cancer patients than in healthy controls, and sometimes, they had the
      same course during anti-tumor therapy, or both improved during an intervention.
      On the contrary, there were some studies suggesting that physical fatigue and
      mental fatigue behaved differently: physical fatigue seemed to be more prominent
      than mental fatigue in some stages of the disease trajectory; several studies
      reported changes in physical fatigue not accompanied by changes in mental fatigue
      during anti-tumor therapy or by interventions aimed to relieve fatigue; and
      physical fatigue and mental fatigue had different correlates. CONCLUSIONS: In
      conclusion, we found some studies in which physical fatigue and mental fatigue
      behaved differently. These findings might indicate that physical fatigue and
      mental fatigue are separate phenomena. To prove this multiple-symptom concept,
      studies on the pathophysiological mechanisms leading either to physical fatigue
      or to mental fatigue are urgently needed.

PMID- 23147805
TI  - A phenanthroimidazole-based fluorescent chemosensor for imaging hydrogen sulfide
      in living cells.
AB  - We have constructed a new fluorescence turn-on chemosensor for hydrogen sulfide
      based on a phenanthroimidazole scaffold, and the novel sensor is suitable for
      imaging hydrogen sulfide in living cells.

PMID- 23147804
TI  - Time-frequency analysis of transient-evoked otoacoustic emissions in children
      exposed to carboplatin chemotherapy.
AB  - The aims of this study were to characterize and quantify time-frequency changes
      in transient-evoked otoacoustic emissions (TEOAEs) recorded in children diagnosed
      with retinoblastoma who were receiving carboplatin chemotherapy. A signal
      processing technique, the wavelet transform (WT), was used to analyze TEOAE
      waveforms in narrow-band frequency components. Ten children (aged 3-72 months)
      diagnosed with unilateral or bilateral retinoblastoma were enrolled in the study.
      TEOAEs were acquired from the children with linear sequences of 70 dB peak
      equivalent SPL clicks. After WT analysis, TEOAE energy, latency and normalized
      energy in the narrow-band frequency components were compared before and during
      carboplatin chemotherapy treatment (average dose 1693 mg/m2). On a group basis,
      no significant differences (p>0.05) in the TEOAE energy, latency or normalized
      energy before and after carboplatin treatment were observed. There were decreases
      in normalized energy on an individual basis in 10 out of 18 ears in the sample.
      Exposure to carboplatin chemotherapy did not cause significant changes in TEOAE
      energy, latency and normalized energy during treatment. However, long-term
      monitoring of hearing with measurements of TEOAEs is warranted, given the risks
      of delayed hearing loss in some children receiving carboplatin chemotherapy.

PMID- 23147806
TI  - Hereditary neuropathy with liability to pressure palsy: an investigation in a
      rare and large Chinese family.
AB  - BACKGROUND: Hereditary neuropathy with liability to pressure palsy (HNPP), mainly
      associated with the peripheral myelin protein 22 (PMP22) gene, is generally an
      autosomal-dominant inherited peripheral neuropathy. The present large family
      including four generations provides an exciting opportunity to gain important
      insights into HNPP in China. PATIENTS AND METHODS: A large 43-member family with
      ten members suspected to be affected by HNPP was studied. Neurologic
      examinations, electrophysiological and neuropathological studies and molecular
      genetic testing were used for these kindred. RESULTS: Clinically, the proband had
      limb hyposthenia and atrophy, and his mother showed declined tendon reflexes in
      the right lower limb. Electrophysiologically, sensory and motor nerve conduction
      velocities were generalized reduced. Sural nerve biopsy for the proband showed
      focal thickesning of the myelin sheaths. Furthermore, real-time quantitative PCR
      demonstrated that the PMP22 gene has a higher Ct value than reference gene in all
      suspected patients. CONCLUSIONS: These results indicated that the family is
      indeed a rare and large pedigree of HNPP caused by the deletion of PMP22 gene.
      Given that the suspected patient in the fourth generation is absent, this family
      is still worthy of further follow-up study.

PMID- 23147807
TI  - Toxicity of diesel contaminated soils to the subantarctic earthworm Microscolex
      macquariensis.
AB  - Several fuel spills have occurred on subantarctic Macquarie Island (54 degrees
      30' S 158 degrees 57' E) associated with storing fuel and generating power for
      the island's research station. The Australian Antarctic Division began full
      scale, on-site remediation of these sites in 2009. To develop appropriate target
      concentrations for remediation, acute and chronic tests were developed with the
      endemic earthworm, Microscolex macquariensis, using avoidance, survival, and
      reproduction as endpoints. Uncontaminated low (3%), medium (11%), and high (38
      48%) carbon content soils from Macquarie Island were used to examine the
      influence of soil carbon on toxicity. Soils were spiked with Special Antarctic
      Blend (SAB) diesel and used either immediately to simulate a fresh spill or after
      four weeks to simulate an aged spill. Earthworms were sensitive to fresh SAB,
      with significant avoidance at 181 mg/kg; acute 14-d survival median lethal
      concentration (LC50) of 103 mg/kg for low carbon soil; and juvenile production
      median effective concentration (EC50) of 317 mg/kg for high carbon soil.
      Earthworms were less sensitive to aged SAB than to fresh SAB in high carbon soil
      for juvenile production (EC50 of 1,753 and 317 mg/kg, respectively), but were
      more sensitive for adult survival (LC50 of 2,322 and 1,364 mg/kg, respectively).
      Using M. macquariensis as a surrogate for soil quality, approximately 50 to 200
      mg SAB/kg soil would be a sufficiently protective remediation target.

PMID- 23147808
TI  - Preventing, assessing, and managing constipation in older adults.

PMID- 23147810
TI  - Recent advances in development of amphotericin B formulations for the treatment
      of visceral leishmaniasis.
AB  - PURPOSE OF REVIEW: Amphotericin B (AmpB) is considered the first-line treatment
      for visceral leishmaniasis in areas in which resistance to antimony is prevalent.
      This review describes recent advances in clinically available and novel drug
      delivery systems of AmpB to treat visceral leishmaniasis. RECENT FINDINGS: Over
      the past two decades, lipid-based AmpB formulations developed to tackle the
      toxicity of AmpB have been used clinically for the treatment of visceral
      leishmaniasis. Liposomal AmpB (AmBisome) has been the most successful lipid
      formulation, and recent clinical studies on visceral leishmaniasis have shown the
      potential of single-dose AmBisome treatment as well as its use in short course
      combinations with other antileishmanial drugs. Current research is focussed on
      the development of more stable and affordable nonlipid formulations of AmpB.
      Although a diverse range of nonlipid-based AmpB formulations have been evaluated,
      none have yet reached the clinic. SUMMARY: Liposomal AmpB (AmBisome) has become a
      standard treatment, by intravenous infusion, for visceral leishmaniasis and the
      basis for new short course treatments. There have been extensive efforts to
      develop new AmpB formulations on the basis of polymers, lipids or physical
      aggregates of AmpB to replace the costly lipid-based formulations. However, no
      nonlipid-based AmpB delivery systems have yet reached the clinic.

PMID- 23147811
TI  - Current world literature.

PMID- 23147809
TI  - Inhibition of prostaglandin D2 production by trihydroxy fatty acids isolated from
      Ulmus davidiana var. japonica.
AB  - The stem and root barks of Ulmus davidiana var. japonica (Ulmaceae) have been
      used to treat inflammatory diseases including mastitis, rhinitis, sinusitis, and
      enteritis. In an ongoing study focused on the discovery of natural anti
      inflammatory compounds from natural products, a methanol extract of the stem and
      root barks of U. davidiana var. japonica showed anti-inflammatory activities.
      Activity-guided fractionation of the methanol extract yielded a new trihydroxy
      fatty acid, 9,12,13-trihydroxyoctadeca-10(Z),15(Z)-dienoic acid (1), and a known
      compound, pinellic acid (2). These two trihydroxy fatty acids 1 and 2 inhibited
      prostaglandin D2 production with IC50 values of 25.8 and 40.8 MUM, respectively.
      These results suggest that 9,12,13-trihydroxyoctadeca-10(Z),15(Z)-dienoic acid
      (1) and pinellic acid (2) are among the anti-inflammatory principles in this
      medicinal plant.

PMID- 23147813
TI  - Iron promoted conjugate addition: implication of the six-centered mechanism based
      on the isolation of the iron-enolate intermediate.
AB  - Treatment of (eta(1)-mesityl)(2)Fe(kappa(2)-TMEDA) (1') with an alpha,beta
      unsaturated carbonyl compound results in 1,4-addition of the mesityl group to
      give an iron enolate quantitatively. The Z-configuration of the enolate suggested
      the six-centered mechanism for the conjugate addition.

PMID- 23147814
TI  - Evaluation of the ion trap MS performance for quantification of flavonoids and
      comparison to UV detection.
AB  - The application of an ion trap mass spectrometer, usually employed for
      identification, has been here systematically evaluated for quantitative analysis
      of various conjugated forms of flavonoids and compared with UV quantification.
      Three MS methods were tested to assess the potential and limits of the ion trap
      for quantification of flavonoids: full-scan experiment MS(2) , isolated ion
      experiment MS, and full-scan experiment MS. The test was performed using nine
      reference standards of flavonoids with six different aglycones: luteolin,
      apigenin, hypolaetin, 4'-O-methylhypolaetin, isoscutellarein and 4'-O
      methylisoscutellarein in the form of 7-O-glucosides and diglucosides, mono or
      diacetylated, isolated from Sideritis scardica. The analytical characteristics of
      the tested MS methods were shown to be comparable to UV with regards to precision
      and accuracy, and superior for selectivity and sensitivity especially when using
      extracted ion chromatograms. Detection limits did not differ significantly
      between the MS methods but were significantly lower than those obtained with UV
      detection by one order of magnitude. Another issue addressed by these results was
      the choice of most suitable standard substances for quantification of flavonoids
      with various substituents attached when using MS. In UV detection, the nature of
      the aglycone is crucial for the absorbance properties, and various derivatives
      can be quantified with the available one with the same aglycone. Here, it was
      shown that in MS detection, one flavone derivative can be quantified using other
      available derivatives with similar substitution pattern with regards to attached
      and acetylated sugars, whereas the nature of the aglycone is not crucial.

PMID- 23147815
TI  - Detection of buffalo mozzarella adulteration by an ultra-high performance liquid
      chromatography tandem mass spectrometry methodology.
AB  - Over the past years, LC-MS-based approaches have gained a growing interest in
      food analysis by using different platforms and methodologies. In particular,
      enhanced selectivity and sensitivity of multiple reaction monitoring (MRM) scan
      function offer powerful capabilities in detecting and quantifying specific
      analytes within complex mixtures such as food matrices. The MRM approach,
      traditionally applied in biomedical research, is particularly suitable for the
      detection of food adulteration and for the verification of authenticity to assure
      food safety and quality, both recognized as top priorities by the European Union
      Commission. Increasingly stringent legislation ensure products safety along every
      step 'from farm to fork', especially for traditional foods designed with the
      Protected Designation of Origin certification. Therefore, there is a growing
      demand of new methodologies for defining food authenticity in order to preserve
      their unique traits against frauds. In this work, an ultra performance liquid
      chromatopgraphy-electrospray ionization-tandem mass spectrometry (MS/MS)
      methodology based on MRM has been developed for the sensitive and selective
      detection of buffalo mozzarella adulteration. The targeted quantitative analysis
      was performed by monitoring specific transitions of the phosphorylated beta
      casein f33-48 peptide, identified as a novel species-specific proteotypic marker.
      The high sensitivity of MRM-based MS and the wide dynamic range of triple
      quadrupole spectrometers have proved to be a valuable tool for the analysis of
      food matrices such as dairy products, thus offering new opportunities for
      monitoring food quality and adulterations.

PMID- 23147816
TI  - Surfactant protein B amount and kinetics in newborn infants: an optimized
      procedure.
AB  - Surfactant protein B (SP-B) plays a key role in surfactant homeostasis affecting
      its biophysical properties and physiological function. Recently, a method to
      measure SP-B amount and kinetics from tracheal aspirates (TAs) became available.
      The main objective of this study was to improve the critical steps of the
      procedure to obtain a better SP-B sensitivity. We administered a 24 h continuous
      infusion of 1 mg/kg/h of 1(13)C-leucine to ten newborn infants. SP-B was isolated
      from serial TAs and its fractional synthesis rate, secretion time, peak time and
      half life were derived from (13)C enrichment curves obtained by gas
      chromatography mass spectrometry. SP-B amount in TAs was also assessed. During
      the extraction step, acidification and organic solvent ratio optimization doubled
      the recovery of SP-B from TAs, so did the elongation of the propylation time
      (from 20 min to 1 h) with enhanced leucine derivatization yield. Measurement of
      (13)C leucine enrichments, and therefore all SP-B kinetics parameters, were
      successfully calculated in all TAs samples due to the increase of SP-B yield. SP
      B amount was 0.29 (0.16-0.41) % of total phospholipids with a minimum value of
      0.08% belonging to one of the respiratory distress syndrome (RDS) patients. In
      conclusion, this new procedure enables accurate determination of SP-B kinetics
      even in the presence of low protein amount like in preterm RDS patients.

PMID- 23147817
TI  - Analysis of chloroquine and metabolites directly from whole-body animal tissue
      sections by liquid extraction surface analysis (LESA) and tandem mass
      spectrometry.
AB  - The rapid and direct analysis of the amount and spatial distribution of exogenous
      chloroquine (CHQ) and CHQ metabolites from tissue sections by liquid extraction
      surface sampling analysis coupled with tandem mass spectrometry (LESA-MS/MS) was
      demonstrated. LESA-MS/MS results compared well with previously published CHQ
      quantification data collected by organ excision, extraction and fluorescent
      detection. The ability to directly sample and analyze spatially resolved
      exogenous molecules from tissue sections with minimal sample preparation and
      analytical method development has the potential to facilitate the assessment of
      target tissue penetration of pharmaceutical compounds, to establish
      pharmacokinetic/pharmacodynamic relationships, and to complement established
      pharmacokinetic methods used in the drug discovery process during tissue
      distribution assessment.

PMID- 23147818
TI  - Study of the electrical connection mechanism of sheathless interface for
      capillary electrophoresis-electrospray ionization-mass spectrometry.
AB  - With the combination of high separation ability of capillary electrophoresis (CE)
      and strong identification ability of mass spectrometry (MS), CE/MS is becoming a
      powerful tool for polar and ionic analytes analysis. Different interfaces have
      been developed to enhance the sensitivity and reliability since the first
      introduction of CE/MS in 1987. A sheathless porous interface based on a new ions
      transferring electric connection technique was reported to be with high
      sensitivity and reliability. In this work, a series of optical and
      electrochemical experiments were designed to study the electric connection
      process. The results indicated that closing CE electrical circuit and applying MS
      spray voltage were achieved by the small ions transferring through the interface
      porous wall. The new electric connection method significantly enhanced the
      sensitivity, resolution and stability of the CE/MS analysis. The interface was
      applied in CE/MS detection of morphine and 6-monoacetylmorphine in urine sample
      and showed an equal sensitivity to LC/MS. With the significant improvement of
      sensitivity and stability, the CE/MS with the new interface showed strong
      potential for the determination of low abundance analytes.

PMID- 23147819
TI  - Modeling bacteriophage amplification as a predictive tool for optimized MALDI-TOF
      MS-based bacterial detection.
AB  - Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry
      (MALDI-TOF MS) is a valuable tool for rapid bacterial detection and
      identification but is limited by the need for relatively high cell count samples,
      which have been grown under strictly controlled conditions. These requirements
      can be eliminated by the natural infection of a viable bacterial species of
      interest with a host-specific phage. This produces a rapid increase in phage
      protein concentrations in comparison to bacterial concentrations, which can in
      turn be exploited as a method for signal amplification during MALDI-TOF MS. One
      drawback to this approach is the requirement for repetitive, time-consuming
      sample preparation and analysis applied over the course of a phage infection to
      monitor phage concentrations as a function of time to determine the MALDI-TOF MS
      detection limit. To reduce the requirement for repeated preparation and analysis,
      a modified phage therapy model was investigated as a means for predicting the
      time during a given phage infection when a detectable signal would occur. The
      modified model used a series of three differential equations composed of
      predetermined experimental parameters including phage burst size and burst time
      to predict progeny phage concentrations as a function of time. Using Yersinia
      pestis with plague diagnostic phage phiA1122 and Escherichia coli with phage MS2
      as two separate, well-characterized model phage-host pairs, we conducted in
      silico modeling of the infection process and compared it with experimental
      infections monitored in real time by MALDI-TOF MS. Significant agreement between
      mathematically calculated phage growth curves and those experimentally obtained
      by MALDI-TOF MS was observed, thus verifying this method's utility for
      significant time and labor reduction.

PMID- 23147820
TI  - Electron transfer dissociation versus collisionally activated dissociation of
      cationized biodegradable polyesters.
AB  - Biodegradable polyesters were ionized by electrospray ionization and
      characterized by tandem mass spectrometry using collisionally activated
      dissociation (CAD) and electron transfer dissociation (ETD) as activation
      methods. The compounds studied include one homopolymer, polylactide and two
      copolymers, poly(ethylene adipate) and poly(butylene adipate). CAD of [M+2Na](2+)
      ions from these polyesters proceeds via charge-remote 1,5-H rearrangements over
      the ester groups, leading to cleavages at the (CO)O-alkyl bonds. ETD of the same
      precursor ions creates a radical anion at the site of electron attachment, which
      fragments by radical-induced cleavage of the (CO)O-alkyl bonds and by
      intramolecular nucleophilic substitution at the (CO)-O bonds. In contrast to CAD,
      ETD produces fragments in one charge state only and does not cause consecutive
      fragmentations, which simplifies spectral interpretation and permits conclusive
      identification of the correct end groups. The radical-site reactions occurring
      during ETD are very similar with those reported for ETD of protonated peptides.
      Unlike multiply protonated species, multiply sodiated precursors form ion pairs
      (salt bridges) after electron transfer, thereby promoting dissociations via
      nucleophilic displacement in addition to the radical-site dissociations typical
      in ETD.

PMID- 23147821
TI  - UPLC-ESI-MS study of the oxidation markers released from tannin depolymerization:
      toward a better characterization of the tannin evolution over food and beverage
      processing.
AB  - Condensed tannins take an important part in the sensory quality of food and
      beverage. Sensory analyses are usually carried out with various tannin fractions
      isolated from food or beverage, and their interpretation are limited by the lack
      of knowledge in the fine and accurate molecular composition of the tannin
      fractions. Besides, the studies of the chemical reactivity conducted in model
      solutions with 'simple' flavanols allow a better understanding of their evolution
      pathways, but they cannot take into account their reactivity as polymers,
      specifically regarding oxidation. In particular, competition between
      intramolecular and intermolecular reactions may strongly impact on the tannin
      structures (size, branching and conformation) and consequently on their
      properties. An ultra-performance liquid chromatography-mass spectrometry
      electrospray ionization mass spectrometer analytical method was thus developed in
      order to identify oxidized tannins generated by autoxidation. Given the
      difficulties to separate and detect tannins with high DP, samples were
      depolymerized by chemical depolymerization prior to analysis. Since the linkages
      created by oxidation are not cleavable in the usual depolymerization conditions
      (contrarily to the original interflavanic linkages), specific oxidation residues
      are released from tannins structures after their autoxidation. Oxidation markers
      of both intermolecular and intramolecular mechanisms have been identified; these
      are mainly dimers and trimers, more or less oxidized, and some contain additional
      hydroxyl groups. Furthermore, the nature of the subunits (extension vs terminal)
      making up these dimers and trimers was clearly established.

PMID- 23147822
TI  - Innovative determination of polar organophosphonate pesticides based on high
      resolution Orbitrap mass spectrometry.
AB  - The determination of compounds showing a very low molecular weight (i.e. < 200
      Da) can be complicated when low-resolution mass spectrometry is used in the
      selected-reaction monitoring mode, since the possible number of product ions is
      reduced and the obtained reactions are not selective enough to overcome
      background noise and/or matrix interferences. In this study, the use of high
      resolution mass spectrometry based on Exactive Orbitrap was applied for the
      determination of a group of polar organophosphonate pesticides and transformation
      products (TPs), which show the aforementioned features, in agricultural soils.
      Namely, glyphosate, glufosinate, ethephon and their TPs, aminomethyl phosphonic
      acid (AMPA), 3-methylphosphinicopropionic acid, N-acetyl-glufosinate and 2
      hydroxyethylphosphonic acid were analyzed. The [M-H](-) ions 168.00564,
      180.04202, 142.96593, 110.00016, 151.01547, 222.05259 and 124.99982 were used,
      respectively, for the detection and identification of the compounds. Confirmation
      was carried out by using accurate mass measurements of ion fragments for each
      compound, from neutral losses of CO(2), H(2)O and H(2)CO (formaldehyde).
      Furthermore, the recently reported tool, relative isotopic mass defect (RDeltam),
      was also used to support the confirmation protocol. The optimized method was
      fully validated at low levels, including the estimation of a not commonly used
      parameter: the limit of confirmation (LOC). This LOC is expressed as the lowest
      concentration of compound that can be confirmed using a fragment or the RDeltam,
      and it ranged from 10 to 50 ug kg(-1) for all compounds. All the data was
      obtained in a single injection. Finally, the method was applied to real soil
      samples, and glyphosate and AMPA were found at 265 ug kg(-1) and 105 ug kg(-1),
      respectively.

PMID- 23147823
TI  - Study of the efficiency for ion transfer through bent capillaries.
AB  - Discontinuous atmospheric pressure interfaces (DAPIs) with bent capillaries
      represent a highly simplified and flexible means for introducing ions into a
      vacuum manifold for mass analysis or gas phase ion reactions. In this work, a
      series of capillaries of different radians and curvatures were used with DAPI for
      studying the impact of the capillary bending on the ion transfer. The variation
      of transfer efficiency was systematically characterized for dry and solvated
      ions. The efficiency loss for dry ions was less than one order of magnitude, even
      with a three-turn bent capillary. The transfer of solvated ions generated by
      electrospray was found to be minimally impacted by the bending of the transfer
      capillary. For multiply protonated ions, the transfer efficiency for ions at
      lower charge states could be relatively well retained, presumably due to the
      lower reactivity associated with proton transfer reaction and the compensation in
      intensity by conversion of ions at higher charge states.

PMID- 23147824
TI  - Direct imaging of single cells and tissue at sub-cellular spatial resolution
      using transmission geometry MALDI MS.
AB  - The need of cellular and sub-cellular spatial resolution in laser desorption
      ionization (LDI)/matrix-assisted LDI (MALDI) imaging mass spectrometry (IMS)
      necessitates micron and sub-micron laser spot sizes at biologically relevant
      sensitivities, introducing significant challenges for MS technology. To this end,
      we have developed a transmission geometry vacuum ion source that allows the laser
      beam to irradiate the back side of the sample. This arrangement obviates the
      mechanical/ion optic complications in the source by completely separating the
      optical lens and ion optic structures. We have experimentally demonstrated the
      viability of transmission geometry MALDI MS for imaging biological tissues and
      cells with sub-cellular spatial resolution. Furthermore, we demonstrate that in
      conjunction with new sample preparation protocols, the sensitivity of this
      instrument is sufficient to obtain molecular images at sub-micron spatial
      resolution.

PMID- 23147825
TI  - Application of MALDI-MS analysis of Rainforest chemodiversity: a keystone for
      biodiversity conservation and sustainable use.

PMID- 23147826
TI  - Quadrupole mass spectroscopy of neon.

PMID- 23147827
TI  - Gas-phase basicity of 2-furaldehyde.
AB  - 2-Furaldehyde (2-FA), also known as furfural or 2-furancarboxaldehyde, is an
      heterocyclic aldehyde that can be obtained from the thermal dehydration of
      pentose monosaccharides. This molecule can be considered as an important
      sustainable intermediate for the preparation of a great variety of chemicals,
      pharmaceuticals and furan-based polymers. Despite the great importance of this
      molecule, its gas-phase basicity (GB) has never been measured. In this work, the
      GB of 2-FA was determined by the extended Cooks's kinetic method from
      electrospray ionization triple quadrupole tandem mass spectrometric experiments
      along with theoretical calculations. As expected, computational results identify
      the aldehydic oxygen atom of 2-FA as the preferred protonation site. The
      geometries of O-O-cis and O-O-trans 2-FA and of their six different protomers
      were calculated at the B3LYP/aug-TZV(d,p) level of theory; proton affinity (PA)
      values were also calculated at the G3(MP2, CCSD(T)) level of theory. The
      experimental PA was estimated to be 847.9 +/- 3.8 kJ mol(-1), the protonation
      entropy 115.1 +/- 5.03 J mol(-1) K(-1) and the GB 813.6 +/- 4.08 kJ mol(-1) at
      298 K. From the PA value, a DeltaH degrees (f) of 533.0 +/- 12.4 kJ mol(-1) for
      protonated 2-FA was derived.

PMID- 23147828
TI  - Study of small chlorine-doped potassium clusters by thermal ionization mass
      spectrometry.
AB  - The theoretical calculations have predicted that nonmetal-doped potassium
      clusters can be used in the synthesis of a new class of charge-transfer salts
      which can be considered as potential building blocks for the assembly of novel
      nanostructured material. In this work, K(n)Cl (n = 2-6) and K(n)Cl(n-1) (n = 3
      and 4) clusters were produced by vaporization of a solid potassium chloride salt
      in a thermal ionization mass spectrometry. The ionization energies (IEs) were
      measured, and found to be 3.64 +/- 0.20 eV for K(2)Cl, 3.67 +/- 0.20 eV for
      K(3)Cl, 3.62 +/- 0.20 eV for K(4)Cl, 3.57 +/- 0.20 eV for K(5)Cl, 3.69 +/- 0.20
      eV for K(6)Cl, 3.71 +/- 0.20 eV for K(3)Cl(2) and 3.72 +/- 0.20 eV for K(4)Cl(3).
      The K(n)Cl(+) (n = 3-6) clusters were detected for the first time in a cluster
      beam generated by the thermal ionization source of modified design. Also, this
      work is the first to report experimentally obtained values of IEs for K(n)Cl(+)
      (n = 3-6) and K(n)Cl(n-1) (+) (n = 3 and 4) clusters. The ionization energies for
      K(n)Cl(+) and K(n)Cl(n-1) (+) clusters are much lower than the 4.34 eV of the
      potassium atom; hence, these clusters should be classified as 'superalkali'
      species.

PMID- 23147829
TI  - Comprehensive characterization of Annonaceous acetogenins within a complex
      extract by HPLC-ESI-LTQ-Orbitrap(r) using post-column lithium infusion.
AB  - Annonaceous acetogenins (AAGs) are a homogenous class of polyketides proposed as
      environmental neurotoxins. Previous dereplication studies of AAGs were limited by
      the use of low-resolution mass spectrometers. Only poor information in terms of
      structures was provided due to the limited fragmentation of protonated or sodium
      cationized species. An innovative approach, using reversed-phase high-performance
      liquid chromatography coupled to a hybrid linear ion trap/orbitrap mass
      spectrometer (LTQ-Orbitrap(r)), was therefore performed. Sensitivity was enhanced
      by post-column infusion of lithium, since AAGs have a high affinity for this
      cation. High level of structural information was obtained from low-energy
      collision-induced dissociation fragmentation experiments of lithium-cationized
      AAGs ([M + Li](+) ions) as demonstrated with purified standards. The method was
      then applied to a total ethyl-acetate extract prepared from commercial soursop
      nectar (Annona muricata L.). The sensitivity, mass accuracy and specific
      fragmentation patterns proved to be particularly useful for characterization of
      the AAGs. Typical structural identification procedure and unexpected observations
      for specific structural types are illustrated, with major and minor compounds.

PMID- 23147830
TI  - Quantification of ginsenosides Rh4 and Rk3 in rat plasma by liquid chromatography
      tandem mass spectrometry: application to a pre-clinical pharmacokinetic study.
AB  - Ginsenoside Rh4 (Rh4) and ginsenoside Rk3 (Rk3) are two active substances
      isolated from the processed Panax species. To further explore their potential
      medicinal application, a reliable liquid chromatography-tandem mass spectrometry
      method (LC/MS/MS) was developed and validated for the quantification of Rh4 and
      Rk3 in rat plasma. Multiple ion monitoring and multiple reaction monitoring
      experiments were performed in negative ionization mode. This LC/MS/MS method had
      good selectivity, sensitivity (lower limit of quantification = 10 ng/mL),
      precision (intra- and inter-day relative standard deviation <= 10.1) and accuracy
      (analytical recovery within 100 +/- 10%). The pharmacokinetic profiles of Rh4 and
      Rk3 were subsequently assessed in Sprague-Dawley rats. Similar to many other
      ginsenosides, the oral bioavailability of Rh4 and Rk3 was unfavorable, and Rh4
      and Rk3 did not have any measurable plasma exposure after oral administration (20
      mg/kg). Fortunately, upon intravenous administration (5 mg/kg), both Rh4 and Rk3
      possessed abundant plasma exposure, moderate clearance (Cl = 50.2 +/- 7.7 and
      23.8 +/- 1.4 mL.min(-1).kg(-1), respectively) and terminal elimination half-life
      (t(1/2 lambdaZ) = 157.2 +/- 65.2 and 99.5 +/- 37.8 min, respectively). As Rh4 and
      Rk3 displayed favorable intravenous pharmacokinetic profiles, further exploration
      on their medicinal application is warranted.

PMID- 23147831
TI  - Reaction pathways of Sc+ (3D, 1D) and Fe+ (6D, 4F) with acetone in the gas phase:
      metal ion oxidation and acetone deethanization.
AB  - The reactions of Sc(+) ((3)D, (1)D) and Fe(+) ((6)D, (4)F) with acetone have been
      investigated in both high- and low-spin states using density functional theory.
      Our calculations have indicated that oxidation of Sc(+) by acetone can take place
      by (1) metal-mediated H migration, (2) direct methyl-H shift and/or (3) C=O
      insertion. The most energetically favorable pathway is metal-mediated H migration
      followed by intramolecular ScO(+) rotation and dissociation. For the
      deethanization of acetone mediated by Fe(+), the reaction occurs on either the
      quartet or sextet surfaces through five elementary steps, i.e. encounter
      complexation, C-C bond activation, methyl migration, C-C coupling and non
      reactive dissociation. The rate-determining step along the quartet-state
      potential-energy surface (PES) is similar to that in the case of Ni(+) ((2)F,
      3d(9)), namely the methyl-migration step. For the sextet-state PES, however, the
      energy barrier for methyl migration is lower than that for C-C bond activation,
      and the rate-determining step is C-C coupling. In general, the low-spin-state
      pathways are lower in energy than the high-spin-state pathways; therefore, the
      reaction pathways for the oxidation of Sc(+) and the Fe(+)-mediated
      deethanization of acetone mostly involve the low-spin states.

PMID- 23147832
TI  - Exploring the intrinsic polar [4+2(+)] cycloaddition reactivity of gaseous
      carbosulfonium and carboxonium ions.
AB  - Gas-phase reactions of model carbosulfonium ions (CH(3)-S(+)=CH(2;) CH(3)CH(2)
      S(+)=CH(2) and Ph-S(+)=CH(2)) and an O-analogue carboxonium ion (CH(3)
      O(+)=CH(2)) with acyclic (isoprene, 1,3-butadiene, methyl vinyl ketone) and
      cyclic (1,3-cyclohexadiene, thiophene, furan) conjugated dienes were
      systematically investigated by pentaquadrupole mass spectrometry. As corroborated
      by B3LYP/6-311 G(d,p) calculations, the carbosulfonium ions first react at large
      extents with the dienes forming adducts via simple addition. The nascent adducts,
      depending on their stability and internal energy, react further via two
      competitive channels: (1) in reactions with acyclic dienes via cyclization that
      yields formally [4+2(+)] cycloadducts, or (2) in reactions with the cyclic dienes
      via dissociation by HSR loss that yields methylenation (net CH(+) transfer)
      products. In great contrast to its S-analogues, CH(3)-O(+)=CH(2) (as well as
      C(2)H(5)-O(+)=CH(2) and Ph-O(+)=CH(2) in reactions with isoprene) forms little or
      no adduct and proton transfer is the dominant reaction channel. Isomerization to
      more acidic protonated aldehydes in the course of reaction seems to be the most
      plausible cause of the contrasting reactivity of carboxonium ions. The CH(2)=CH
      O(+)=CH(2) ion forms an abundant [4+2(+)] cycloadduct with isoprene, but similar
      to the behavior of such alpha,beta-unsaturated carboxonium ions in solution,
      seems to occur across the C=C bond.

PMID- 23147833
TI  - Direct imaging of single cells and tissue at sub-cellular spatial resolution
      using transmission geometry MALDI MS.
AB  - Discussions about MALDI imaging frequently turn to the topic of spatial
      resolution and the eff orts of some researchers in the field to push towards
      routine imaging of tissue sections at a cellular scale. Some factors that limit
      resolution are, the size of the focused desorption laser beam and analyte
      delocalization from the solution-based sample preparation. With solvent-free
      matrix application techniques analyte delocalization is less of a concern and the
      size of the focused laser is the major limiter of spatial resolution. In the
      Special Feature, Professor Caprioli and co-workers at Vanderbilt University
      demonstrate a new instrumental approach for improving spatial resolution. They
      have modifi ed a MALDI-TOF system to use transmission-mode geometry, in which the
      desorption laser is focused onto the matrix crystals from behind and through the
      target and sample rather than conventional front-side illumination where the
      laser is focused onto the crystals directly. They show that by moving the laser
      source behind the sample target, they can optimize the laser focus to achieve
      cellular resolution for MALDI imaging.

PMID- 23147834
TI  - Ciliary neurotrophic factor (CNTF) promotes skeletal muscle progenitor cell (MPC)
      viability via the phosphatidylinositol 3-kinase-Akt pathway.
AB  - Muscle progenitor cells (MPCs) are currently being investigated as cellular
      vectors to deliver neurotrophic factor (NF) for the promotion of re-innervation
      after axonal injury. Ideally NF delivery in such a model would enhance axonal
      regeneration while simultaneously promoting MPC viability. To date, insulin-like
      growth factor 1 (IGF-1) is one of the few NFs known to promote both re
      innervation and MPC viability. We herein identify ciliary neurotrophic factor
      (CNTF) as a factor that promotes MPC viability in culture, and demonstrate CNTF
      to impart greater viability effects on MPCs than IGF-1. We demonstrate that
      pharmacological inhibition via LY294002 results in abrogation of CNTF-mediated
      viability, suggesting that the CNTF-mediated MPC viability benefit occurs via the
      PI3-Akt pathway. Finally, we employ a genetic model, establishing MPC cultures
      from mice deficient in class IA PI-3 K (p85alpha(-/-) ) mice, and demonstrate
      that the viability benefit imparted by CNTF is completely abrogated in PI-3 K
      deficient MPCs compared to wild-type controls. In summary, our investigations
      define CNTF as a promoter of MPC viability beyond IGF-1, and reveal that the CNTF
      mediated MPC viability effects occur via the PI3-Akt pathway.

PMID- 23147835
TI  - Temperature-controlled self-assembling structure with selective guest-recognition
      at the liquid-solid interface.
AB  - We investigate the influence of temperature on the self-assembly of 2,6,11
      tricarboxydecyloxy-3,7,10-triundecyloxy triphenylene (asym-TTT) adsorbed on HOPG
      using scanning tunneling microscopy (STM) at the liquid/solid interface. We show
      that the packing structures of 2D self-assembled asym-TTT can be precisely tuned
      by adjusting the substrate temperature. The temperature change from 20  degrees C
      to 35  degrees C induces two phase transitions and increment in the packing
      density from 0.161 to 0.179 molecules per nm(2). The density-functional theory
      (DFT) calculations reveal that their interaction energies are similar. In
      particular, the experimental findings further illustrate the preferential
      adsorption of guest molecules, such as phthalocyanine, only in the domain of more
      close packing structures.

PMID- 23147836
TI  - Spiralisones A-D: acylphloroglucinol hemiketals from an Australian marine brown
      alga, Zonaria spiralis.
AB  - An intertidal sample of the Australian marine brown alga, Zonaria spiralis,
      exhibited promising kinase inhibitory and antibacterial activity. Chemical
      analysis returned six phloroglucinol-derived lipids, the new hemiketal
      spiralisones A-D (1-4) and the known chromones 5-6, and the known
      norsesquiterpenoid apo-9'-fucoxanthinone (7). Structures 1-7 were assigned on the
      basis of detailed spectroscopic analysis, biosynthetic considerations and total
      synthesis. Spiralisones undergo facile acid-mediated dehydration to yield the
      corresponding chromones, revealing for the first time that brown algal chromones
      may be handling artifacts rather than natural products. Hemiketals 1 and 2, and
      chromone 6, displayed inhibitory activity against the neurodegenerative disease
      kinase targets CDK5/p25, CK1delta and GSK3beta, while hemiketals 1, 3 and 4, and
      chromone 6, displayed growth inhibitory activity against the Gram-positive
      bacteria Bacillus subtilis (ATCC 6051 and 6633). The promising kinase inhibitory
      and antibacterial properties of the Z. spiralis extract were attributed to the
      cumulative effect of many moderately potent phloroglucinol-derived lipid co
      metabolites.

PMID- 23147837
TI  - Experimental exposure of eggs to polybrominated diphenyl ethers BDE-47 and BDE-99
      in red-eared sliders (Trachemys scripta elegans) and snapping turtles (Chelydra
      serpentina) and possible species-specific differences in debromination.
AB  - Polybrominated diphenyl ethers (PBDEs) are a bioaccumulative, persistent, and
      toxic class of flame retardants that can potentially impact turtles in natural
      habitats via exposure through maternal transfer. To simulate maternal transfer in
      the present study, PBDE congeners BDE-47 and BDE-99 were topically applied to the
      eggshell and were allowed to diffuse into the egg contents of the red-eared
      slider (Trachemys scripta elegans) and snapping turtle (Chelydra serpentina).
      Eggs were topically dosed over 8 d to achieve a target concentration of 40 ng/g
      in the egg contents. Transfer efficiency was higher for BDE-47 than for BDE-99 in
      the red-eared sliders (25.8 +/- 1.9% vs 9.9 +/- 1.1%) and snapping turtles (31.3
      +/- 1.6% vs 12.5 +/- 1.4%), resulting in greater BDE-47 and lower BDE-99 egg
      content concentrations relative to the 40 ng/g target. However, only 25.8 and
      31.3% of the total BDE-47 and 9.9 and 12.5% of the total BDE-99 dose applied
      could be accounted for in the red-eared slider and snapping turtle egg contents,
      respectively. Additionally, increased BDE-47 in red-eared slider egg contents
      dosed with only BDE-99 indicate that BDE-99 might have been debrominated to BDE
      47. The efficacy of topical dosing for administering desired embryonic exposures
      is clearly affected by the chemical properties of the applied compounds and was
      more successful for BDE-47 in both species.

PMID- 23147839
TI  - Canalith repositioning procedures among 965 patients with benign paroxysmal
      positional vertigo.
AB  - BACKGROUND: Canalith repositioning procedure (CRP) has increasingly been utilized
      for the last 15 years for the treatment of benign paroxysmal positional vertigo
      (BPPV). We assess the short- and long-term efficacy of CRP on the treatment of
      patients with BPPV. METHODS: Nine hundred sixty-five patients (481 men and 484
      women, from 18 to 87 years of age) were enrolled in this prospective study during
      1995-2010. Inclusion criteria were a patient history compatible with BPPV and a
      positive provocative maneuver (either Dix-Hallpike or Roll test). Reported
      duration of symptoms at the time of their first examination varied from 1 day to
      18 months. Variants of the Epley and Barbeque maneuver were used for posterior
      and anterior canal involvement, and horizontal canal involvement, respectively.
      Short-term follow-up was obtained 48 h and 7 days after initial treatment,
      whereas long-term follow-up was obtained at repeated 6-month intervals. RESULTS:
      Symptoms subsided immediately in 819 patients (85%) by the first CRP. Only 19
      patients (2%) required CRP more than 3 times. Patients' mean follow-up was 74
      months; symptom recurrence was noted in 139 patients. A statistically
      significantly higher recurrence rate was noted in elderly people or those with
      head trauma or a history of vestibular neuropathy (p<0.001). CONCLUSIONS: This
      study provides class IV evidence that CRP remains an efficient and long-lasting
      noninvasive treatment for BPPV, especially for younger patients without a history
      of head trauma or vestibular neuropathy. Elderly people have a significantly
      higher recurrence rate requiring additional education to minimize potential
      morbidity of their falls.

PMID- 23147838
TI  - A chemically-defined screening platform reveals behavioral similarities between
      primary human mesenchymal stem cells and endothelial cells.
AB  - Chemically defined substrates, which rigorously control protein-surface and cell
      surface interactions, can be used to probe the effects of specific biomolecules
      on cell behavior. Here we combined a chemically-defined, array-based format with
      automated, time-lapse microscopy to efficiently screen cell-substrate
      interactions. Self-assembled monolayers (SAMs) of alkanethiolates bearing
      oligo(ethylene glycol) units and reactive terminal groups were used to present
      cell adhesion peptides while minimizing non-specific protein interactions.
      Specifically, we describe rapid fabrication of arrays of 1 mm spots, which
      present varied densities of the integrin-binding ligand Gly-Arg-Gly-Asp-Ser-Pro
      (GRGDSP). Results indicate that cell attachment, cell spreading, and
      proliferation exhibit strong dependencies on GRGDSP density for both human
      mesenchymal stem cells (hMSCs) and human umbilical vein endothelial cells
      (HUVECs). Furthermore, relative spreading and proliferation over a broad range of
      GRGDSP densities were similar for both primary cell types, and detailed
      comparison between cell behaviors identified a 1 : 1 correlation between
      spreading and proliferation for both HUVECs and hMSCs. Finally, time-lapse
      microscopy of SAM arrays revealed distinct adhesion-dependent migratory behaviors
      for HUVECs and hMSCs. These results demonstrate the benefits of using an array
      based screening platform for investigating cell function. While the proof-of
      concept focuses on simple cellular properties, the quantitative similarities
      observed for hMSCs and HUVECs provides a direct example of how phenomena that
      would not easily be predicted can be shown to correlate between different cell
      types.

PMID- 23147841
TI  - Stroke: finding atrial fibrillation after cryptogenic stroke.

PMID- 23147843
TI  - Multiple sclerosis: oral BG12 for treatment of relapsing-remitting MS.

PMID- 23147848
TI  - Neurodegenerative disease: neural stem cell degeneration in PD linked to nuclear
      defects.

PMID- 23147846
TI  - Neural interfaces for the brain and spinal cord--restoring motor function.
AB  - Regaining motor function is of high priority to patients with spinal cord injury
      (SCI). A variety of electronic devices that interface with the brain or spinal
      cord, which have applications in neural prosthetics and neurorehabilitation, are
      in development. Owing to our advancing understanding of activity-dependent
      synaptic plasticity, new technologies to monitor, decode and manipulate neural
      activity are being translated to patient populations, and have demonstrated
      clinical efficacy. Brain-machine interfaces that decode motor intentions from
      cortical signals are enabling patient-driven control of assistive devices such as
      computers and robotic prostheses, whereas electrical stimulation of the spinal
      cord and muscles can aid in retraining of motor circuits and improve residual
      capabilities in patients with SCI. Next-generation interfaces that combine
      recording and stimulating capabilities in so-called closed-loop devices will
      further extend the potential for neuroelectronic augmentation of injured motor
      circuits. Emerging evidence suggests that integration of closed-loop interfaces
      into intentional motor behaviours has therapeutic benefits that outlast the use
      of these devices as prostheses. In this Review, we summarize this evidence and
      propose that several known plasticity mechanisms, operating in a complementary
      manner, might underlie the therapeutic effects that are achieved by closing the
      loop between electronic devices and the nervous system.

PMID- 23147849
TI  - Stroke: could the neuroprotective drug NA-1 limit ischaemic brain damage after
      stroke?

PMID- 23147851
TI  - Epilepsy: perampanel-new promise for refractory epilepsy?

PMID- 23147853
TI  - Genetics: mutations in potassium channel KCNT1-a novel driver of epilepsy
      pathogenesis.

PMID- 23147854
TI  - Neuro-oncology: treatment decisions in elderly patients with glioblastoma.

PMID- 23147855
TI  - White matter disease: myelination achieved by transplanted neural stem cells.

PMID- 23147856
TI  - Evaluation and optimisation of preparative semi-automated electrophoresis systems
      for Illumina library preparation.
AB  - Size selection can be a critical step in preparation of next-generation
      sequencing libraries. Traditional methods employing gel electrophoresis lack
      reproducibility, are labour intensive, do not scale well and employ hazardous
      interchelating dyes. In a high-throughput setting, solid-phase reversible
      immobilisation beads are commonly used for size-selection, but result in quite a
      broad fragment size range. We have evaluated and optimised the use of two semi
      automated preparative DNA electrophoresis systems, the Caliper Labchip XT and the
      Sage Science Pippin Prep, for size selection of Illumina sequencing libraries.

PMID- 23147857
TI  - Intraocular lens power measured by partial coherence interferometry.
AB  - PURPOSE: To compare the accuracy of the intraocular lens (IOL) power calculation
      of the Zeiss IOLMaster versus conventional automated keratometry and contact
      acoustic biometry after personalized optimization. METHODS: Three hundred twenty
      eyes of 249 patients consecutively receiving phacoemulsification and IOL
      implantation with the sutureless clear cornea approach were enrolled.
      Preoperative biometry was derived from the Zeiss IOLMaster and an acoustic device
      (Alcon OcuScan RxP), and keratometry was measured by the Zeiss IOLMaster and a
      conventional automated keratometer (Topcon KR-8800). One month after surgery,
      refraction was measured and the predicted refractive errors were calculated with
      personalized optimization. RESULTS: For eyes responsive to all devices, IOLMaster
      biometry + IOLMaster keratometry had the best predictability for postoperative
      refraction, with a mean absolute error (MAE) of 0.38 +/- 0.28D, followed by
      OcuScan RxP biometry + IOLMaster keratometry (MAE, 0.49 +/- 0.34D) and OcuScan
      RxP biometry + KR-8800 keratometry (MAE, 0.54 +/- 0.37D) (P < 0.05 for all paired
      comparisons). For eyes that could not be measured by IOLMaster biometry, the MAE
      was smaller with IOLMaster keratometry (0.62 +/- 0.56D) than with KR-8800
      keratometry (0.57 +/- 0.52D) (P = 0.03). The variables of age, diabetes mellitus,
      severity of cataract, axial length, and corneal curvature were unrelated to the
      predictability of postoperative refraction. CONCLUSIONS: The Zeiss IOLMaster
      yielded more accurate refractive outcomes than the conventional automated
      keratometry and contact acoustic biometry after personalized optimization. For
      eyes irresponsive to axial length measurement by the IOLMaster, keratometry of
      the IOLMaster was still superior to conventional automated keratometry.

PMID- 23147858
TI  - A brownish verrucous plaque on the intergluteal cleft: porokeratosis
      ptychotropica.

PMID- 23147859
TI  - Health inequality--determinants and policies. Editor-in-Chief's introductory
      comments.

PMID- 23147860
TI  - Health Inequality--determinants and policies. Summary.

PMID- 23147862
TI  - Health Inequality--determinants and policies. Foreword.

PMID- 23147863
TI  - Health inequality--determinants and policies.

PMID- 23147864
TI  - Lewis acid-catalyzed oxidation of benzylamines to benzamides.
AB  - A novel Lewis acid-catalyzed oxidation of benzylamines to the corresponding
      amides has been developed. Using 10 mol% of ZnBr(2) or FeCl(3) as the catalyst
      and TBHP as the oxidant, amides were produced under mild conditions.

PMID- 23147866
TI  - Current world literature.

PMID- 23147865
TI  - Effect of arctiin on glomerular filtration barrier damage in STZ-induced diabetic
      nephropathy rats.
AB  - Diabetic nephropathy (DN) is the major life-threatening complication of diabetes.
      Abnormal permeability of glomerular basement membrane plays an important role in
      DN pathogenesis. This study was performed to assess the effect of arctiin, the
      lignan constituent from Arctium lappa L., on metabolic profile and aggravation of
      renal lesions in a rat model of streptozotocin (STZ)-induced DN. STZ-induced
      diabetic rats were treated with arctiin at the dosage of 60 or 40 mg/kg/day via
      intraperitoneal injection for 8 weeks. Blood glucose and 24-h urinary albumin
      content were measured, and kidney histopathological changes were monitored. RT
      PCR and immunohistochemistry were used to detect the mRNA and protein levels of
      nephrin, podocin and heparanase (HPSE) in the kidney cortex of rats,
      respectively. Treatment with arctiin significantly decreased the levels of 24-h
      urinary albumin, prevented the sclerosis of glomeruli and effectively restored
      the glomerular filtration barrier damage by up-regulating the expression of
      nephrin and podocin and down-regulating HPSE level. Our studies suggest that
      arctiin might be beneficial for DN. The effects of arctiin on attenuating
      albuminuria and glomerulosclerosis are possibly mediated by regulating the
      expression of nephrin and podocin and HPSE in STZ-induced diabetic rats.

PMID- 23147869
TI  - Extraction of sediment-associated polycyclic aromatic hydrocarbons with granular
      activated carbon.
AB  - Addition of activated carbon (AC) to sediments has been proposed as a method to
      reduce ecotoxicological risks of sediment-bound contaminants. The present study
      explores the effectiveness of granular AC (GAC) in extracting polycyclic aromatic
      hydrocarbon (PAH) from highly contaminated sediments. Four candidate GAC
      materials were screened in terms of PAH extraction efficiency using single-step
      24-h GAC extractions, with traditional 24-h Tenax extraction as a reference.
      Subsequently, sorption of native PAHs to the best performing GAC 1240W (0.45-1.70
      mm) was studied for sediment only and for GAC-sediment mixtures at different GAC
      sediment weight ratios, using 76-um polyoxymethylene (POM) passive samplers.
      Granular AC sorption parameters for PAHs were determined by subtracting the
      contribution of PAH sorption to sediment from PAH sorption to the GAC-sediment
      mixture. It appears that the binding of PAHs and the effectiveness of GAC to
      reduce sediment porewater concentrations were highly dependent on the GAC
      sediment mixing ratio and hydrophobicity of the PAH. Despite the considerable
      fouling of GAC by organic matter and oil, 50 to 90% of the most available PAH was
      extracted by the GAC during a 28-d contact time, at a dose as low as 4%, which
      also is a feasible dose in field-scale applications aimed at cleaning the
      sediment by GAC addition and removal.

PMID- 23147868
TI  - Pdx1 and controlled culture conditions induced differentiation of human amniotic
      fluid-derived stem cells to insulin-producing clusters.
AB  - This study investigated the differentiation of human amniotic fluid-derived stem
      cells (hAFSCs) into insulin-producing clusters in vitro. Adenovirally-delivered
      mouse Pdx1 (Ad-Pdx1) induced human Pdx1 expression in hAFSCs and enhanced the
      coordinated expression of downstream beta-cell markers. When Ad-Pdx1-transduced
      hAFSCs were sequentially treated with activin A, bFGF and nicotinamide and the
      culture plate surface coated with poly-l-ornithine, the expression of islet
      associated human mRNAs for Pdx1, Pax6, Ngn3 and insulin was increased. C-peptide
      ELISA confirmed that Ad-Pdx1-transduced hAFSCs processed and secreted insulin in
      a manner consistent with that pathway in pancreatic beta-cells. To sustain the
      beta-cell-like phenotype and investigate the effect of three-dimensional (3D)
      conformation on the differentiation of hAFSCs, Pdx1-transduced cells were
      encapsulated in alginate and cultured long-term under serum-free conditions. Over
      2 weeks, partially differentiated hAFSC clusters increased in size and increased
      insulin secretion. Taken together, these data demonstrate that ectopic Pdx1
      expression initiates pancreatic differentiation in hAFSCs and that a beta-cell
      like phenotype can be augmented by culture conditions that mimic the stromal
      components and 3D geometry associated with pancreatic islets.

PMID- 23147870
TI  - Plasma cysteine/cystine reduction potential correlates with plasma creatinine
      levels in chronic kidney disease.
AB  - BACKGROUND/AIMS: Oxidative stress has been considered a nontraditional risk
      factor for cardiovascular disease in the chronic kidney disease (CKD) population,
      possibly triggered by uremic toxicity. METHODS: A chromatographic method with
      coulometric detection was adapted to directly and simultaneously determine
      cysteine (Cys) and cystine (Cyss) in plasma samples. Healthy subjects and CKD
      subjects in different stages were analyzed. The free Cys and free Cyss levels in
      their plasma were determined, and the reduction potential [Eh(Cyss/2Cys)] was
      calculated with the Nernst equation. RESULTS: Healthy plasma presented
      Eh(Cyss/2Cys) of -123 +/- 7 mV. Plasma Eh(Cyss/2Cys) correlated significantly
      with creatinine levels (p < 0.0001, r = 0.62). CONCLUSION: Plasma Eh(Cyss/2Cys)
      correlated with increased levels of plasma creatinine, supporting the view that
      uremia triggers oxidative stress. In addition, it may be used as a quantitative
      oxidative stress biomarker in uremic conditions.

PMID- 23147871
TI  - Clinical review of treatment options for major depressive disorder in patients
      with coronary heart disease.
AB  - It is established that the prevalence of major depressive disorder (MDD) in
      coronary heart disease (CHD) populations is high and is associated with increased
      mortality. In this systematic review, we examined the evidence for the effective
      treatment of MDD in CHD patients by reviewing randomized control trials (RCTs)
      between 1980 and 2011 and then assessing whether these treatments were clinically
      meaningful. A total of 8 RCTs were retrieved. Sertraline, citalopram, and
      mirtazapine were safe from a cardiac perspective, but only sertraline and
      citalopram were clearly more effective than placebo in CHD patients with moderate
      to-severe type, recurrent MDD, or MDD episode onset before the CHD event.
      Augmenting sertraline with omega-3 fatty acids did not result in superior
      depression outcomes. Cognitive-behavioral therapy was equivocally superior to
      usual care. Interpersonal psychotherapy was only superior to clinical management
      in patients with high baseline functional status. Exercise is a potential
      treatment for those with mild depression.

PMID- 23147872
TI  - Chronic exposure of rats to native high altitude increases in blood pressure via
      activation of the renin-angiotensin-aldosterone system.
AB  - OBJECTIVE: To study the effect of chronic exposure to native high altitude (HA)
      on blood pressure, and to investigate the underlying mechanism of action.
      METHODS: This study was carried out between February and April 2011. A total of
      20 male rats were divided   into 2 groups (n=10 rats). The low altitude (LA)
      group were rats born and lived in an LA environment at King Saud University,
      College of Pharmacy, Riyadh, Kingdom of Saudi Arabia (KSA), and the HA group were
      rats born in the same LA area, then acclimatized to HA area in Physiology
      Department, King Khalid University, College of Medicine, Abha, KSA for 90 days.
      At the end of day 90, hematocrit, plasma renin activity, aldosterone,
      norepinephrine and vasopressin levels were determined in both groups. Invasive
      arterial blood pressure was also measured, and fractional excretion of sodium
      (FENa), and potassium (FEK) were calculated. The quantitative real time
      polymerase chain reaction of renin was carried out in the kidneys of both rat
      groups. RESULTS: When compared to LA native rats, HA rats exhibited a significant
      increase in systolic and diastolic blood pressure with a significant increase in
      renin plasma activity as well as an increase in the levels of aldosterone,
      norepinephrine, and vasopressin. Furthermore, HA rats showed a significant
      increase in renin expression in their kidneys, as well as decreased FENa.
      CONCLUSION: Data shows that prolonged exposure to HA results in elevated blood
      pressure precipitated by the activation of the renin-angiotensin-aldosterone
      system.

PMID- 23147873
TI  - Immunological studies of oxidized superoxide dismutase in patients with systemic
      lupus erythematosus. Correlation with disease induction and progression.
AB  - OBJECTIVE: To investigate the status and contribution of oxidized superoxide
      dismutase (SOD) in systemic lupus erythematosus (SLE), and to explore whether
      oxidized-SOD has a role in disease induction and progression. METHODS: This study
      was performed in the College of Medicine, Qassim University, Buraidah, Kingdom of
      Saudi Arabia between October 2011 and May 2012. The study was designed to explore
      the role of oxidized-SOD in SLE autoimmunity. The SOD was modified by reactive
      oxygen species (ROS) and characterized. Binding characteristics of autoantibodies
      in SLE patients (n=50) with varying levels of disease activity according to the
      SLE Disease Activity Index (SLEDAI) against ROS-modified-SOD (ROS-SOD) were
      screened by immunoassays and the results were compared with healthy age-matched
      controls (n=34). RESULTS: The ROS caused extensive damage of SOD. Serum analysis
      showed significantly higher levels of anti-ROS-SOD antibodies in SLE patients
      compared with controls. Interestingly, not only was there an increased number of
      subjects positive for anti-ROS-SOD antibodies, but also the levels of these
      antibodies were significantly higher among SLE patients, whose SLEDAI scores were
      >/=20. In addition, a significant correlation was observed between the levels of
      anti-ROS-SOD antibodies and the SLEDAI score (r=0.796). CONCLUSION: Our findings
      show an association between oxidized-SOD and SLE. The stronger response observed
      in patients with higher SLEDAI scores suggests that oxidized-SOD may be a useful
      biomarker in evaluating the progression of SLE and in elucidating the mechanisms
      of disease pathogenesis.

PMID- 23147874
TI  - Use of pressure volume loop closure to check for endotracheal tube cuff function.
      Randomized clinical trial.
AB  - OBJECTIVE: To assess the efficacy of pressure volume loop (PV-L) closure as an
      indicator of adequate endotracheal tube cuff (ETTc) function, and to compare this
      with commonly used methods of checking cuff pressure. METHODS: We conducted a
      randomized clinical trial at the Department of Anesthesia, King Abdulaziz
      University Hospital, Jeddah, Kingdom of Saudi Arabia from October 2011 to
      February 2012. One hundred and forty patients were intubated, and the ETTc was
      inflated using one of 3 techniques. The intubating anesthesiologist inflated the
      cuff at his discretion until he detected no further air leak in the first
      technique. In the second technique, we maintained the ETTc pressure at 20
      centimeter water, while the third technique used PV-L closure. RESULTS: The PV-L
      technique required lower amounts of air to inflate the ETTc than the other 2
      techniques (3.89+/-0.26 for PV-L versus 4.4+/-0.36 for fixed preset pressure, and
      5.26+/-0.46 for pilot balloon palpation, p=0.00001) and the mean cuff pressure
      was lower than other techniques (18.67+/-0.72 for PV-L versus 20 for fixed preset
      pressure, and 33.48+/-3.49 for pilot balloon palpation, p=0.00001). CONCLUSION:
      The PV-L closure technique is an alternative way to check for ETTc function with
      a significantly lower ETTc pressure and volume than those recorded with a
      manually inflated cuff, or with preset cuff pressure of 20 cmH2O.

PMID- 23147875
TI  - Difference between continuous positive airway pressure via mask therapy and
      incentive spirometry to treat or prevent post-surgical atelectasis.
AB  - OBJECTIVE: To assess the effect of early use of continuous positive airway
      pressure (CPAP) therapy to treat or prevent acute atelectasis in post-operative
      cardiac patients particularly smokers and elderly patients. METHODS: A pilot
      study suggested enrolling at least 32 participants in each group to be
      significant. One hundred and eight patients from King Fahd Armed Forces Hospital,
      Jeddah, Kingdom of Saudi Arabia who met the inclusion criteria participated in
      this study conducted between March 2010 and March 2011. The participants were
      divided randomly into 3 groups, incentive spirometry (IS) therapy, and CPAP
      therapy every 2 (CPAP 2 hrs), or 4 hours (CPAP 4 hrs). Inspiratory capacity (IC)
      was used to compare the 3 therapy regimes. Simultaneously, respiratory rate (RR),
      heart rate (HR) and oxygen saturation (SpO2) were measured for all groups.
      Failure was defined as requiring intubation, bi-level positive airway pressure,
      or added chest physiotherapy. RESULTS: Thirty-six patients participated in each
      group (98 male and 10 female, with a mean age of 62+/-9.3 years). The IC
      increased significantly in the CPAP 2 hrs group when compared with the control
      group or the CPAP 4hrs group. The SpO2 decreased significantly in the control
      group and the CPAP 4 hrs groups when compared with the CPAP 2 hrs group. Also,
      there were no significant differences in RR and HR between all groups.
      CONCLUSION: Early use of CPAP via mask therapy for half an hour every 2 hours had
      better outcomes to re-open collapsed alveoli after cardiac surgery.

PMID- 23147876
TI  - Role of growth hormone and insulin-like growth factor-I in hyperandrogenism and
      the severity of acne vulgaris in young males.
AB  - OBJECTIVE: To evaluate the association of growth hormone (GH), and insulin-like
      growth factor-1(IGF-1) in the production of male sex hormones   and the severity
      of acne in Iraqi male patients, and to assess their role in development of
      secondary hyperlipidemia in such patients. METHODS: We conducted this case
      control study and single-center measurement of hormones and selected biochemical
      parameters in a cohort of volunteer males in the Department of Biochemistry
      College of Medicine, Baghdad University, and in the Dermatology Department,
      Baghdad Teaching Hospital, Iraq, from January 2010 to November 2010. RESULTS: The
      mean serum levels of GH and IGF-1 of severe acne patients were significantly
      increased when compared with mild-, moderate acne patients, and healthy controls
      (p=0.0001). Also, the mean serum total testosterone, androstenedione, and
      dehydroepiandrosterone sulfate (DHEAS) levels were significantly increased in
      severe acne compared with those of mild- (p=0.0001), moderate acne patients
      (p=0.005), and healthy males (p=0.0001). The mean values of lipid parameters
      significantly differed in severe acne patients in comparison with other acne
      groups and controls (p=0.004). The results also revealed a significant
      correlation between the studied parameters. CONCLUSION: The study showed a
      significant elevation of serum GH and IGF-1, which enhanced androgen hormone
      production and the development of severe acne. These patients may develop
      hyperlipidemia secondary to their hyperandrogenism.

PMID- 23147877
TI  - Evaluation of the effect of Bupivacaine (Marcaine) in reducing early post
      tonsillectomy pain.
AB  - OBJECTIVE: To evaluate the effectiveness of bupivacaine as topically applied in
      reducing post tonsillectomy pain within the first 24 hours. METHODS: This
      prospective, randomized, placebo-controlled, intra-individual, single-blind study
      was conducted at the Otolaryngology Department, King Abdulaziz University
      Hospital, King Saud University, Riyadh, Kingdom of Saudi Arabia from October 2009
      until March 2010. Thirty-five patients underwent cold knife tonsillectomy. One
      tonsillar fossa was packed with gauze soaked in plain 0.25% bupivacaine, while
      the other tonsillar fossa was packed with gauze soaked in normal saline (the
      control side). Both gauzes were applied for 5 minutes. The patients' pain was
      evaluated on each side using the visual analog scale at 2, 4, 6, 12, and 24 hours
      post-operatively. RESULTS: The reduction in pain at 2 and 4 hours was
      statistically insignificant compared with the control side. However, at 6, 12,
      and 24 hours post operatively, the reduction of pain was statistically
      significant. CONCLUSION: Topical application of bupivacaine at a 0.25%
      concentration appears to a considerable degree of analgesia within the first 24
      hours post tonsillectomy.

PMID- 23147878
TI  - Assessment of hepatitis B vaccination and compliance with infection control among
      dentists in Saudi Arabia.
AB  - OBJECTIVE: To evaluate hepatitis B virus (HBV) vaccine coverage and the use of
      infection control among dentists in Saudi Arabia. METHODS: This cross-sectional
      study was carried out during the Third International Conference at the King
      Abdulaziz University Faculty of Dentistry, held on March 2012 in Jeddah, Saudi
      Arabia. Saudi or expatriate dentists working in Saudi Arabia were included in the
      study. The questionnaires were designed to meet the objective of the study.
      RESULTS: A total of 402 dentists of whom 176 (44%) were male and 226 (56%) female
      took part in this study. Their mean age was 37.4 years. In all, 246 (61%) were
      general dentists and 156 (39%) specialists. Four-fifths (80.5%) of them had been
      vaccinated. Almost half (48.5%) had experience of needle stick injury, but none
      reported having been infected with HBV. Among the vaccinated dentists, 186
      (57.5%) had not been screened for HBV antibodies. Younger dentists were more
      particular about vaccination and more careful in using protective wear. There was
      an association between protective barriers and HBV vaccination, but there was no
      association between history of needle stick injury and vaccination. CONCLUSION:
      Dental healthcare workers have a high risk of infection with HBV due to the
      nature of their work; so there should be a mandatory program to vaccinate
      dentists against HBV and to ensure application of protective measures during
      their practice.

PMID- 23147879
TI  - Congenital heart defects in Down syndrome patients from western Saudi Arabia.
AB  - OBJECTIVE: To characterize congenital heart defects in individuals with Down
      syndrome (DS) in the Western Region of Saudi Arabia, and compare with studies
      from other regions of Saudi Arabia and with international figures. METHODS: We
      conducted a prospective study including all patients attending the DS clinic at
      King Abdulaziz University Hospital, Jeddah, Kingdom of Saudi Arabia between
      October 2007 and October 2011. All patients underwent full history and physical
      evaluations, dysmorphologic assessment, chromosomal studies, and
      echocardiography. RESULTS: A total of 130 individuals (59% males and 41% females)
      with ages ranging between 0-33 years (mean=5+/-4.9) were included. Most
      individuals (90.9%) had trisomy 21 due to non-disjunction, 5.05% due to
      Robertsonian translocation, and 4% had mosaicism. Congenital heart defects were
      found in 86.8% of patients. The majority 71/92 (77%) showed combined cardiac
      defects, while 21/92 (23%) of DS patients had isolated congenital heart defects
      (CHD). The most frequent CHDs detected in this study were: patent ductus
      arteriosis in 44/92 (47.8%), atrial septal defect in 38/92 (41.3%), trivial
      tricuspid regurge in 31/92 (33.7%), ventricular septal defect in 27/92 (29.3%),
      and patent foramen oval in 26/92 (28.3%). CONCLUSION: We found a higher incidence
      of CHDs among DS individuals from the Western Region, compared to national and
      international figures. We detected more combined CHD and a different pattern of
      distribution.

PMID- 23147880
TI  - Nutritional assessment and obesity in Down syndrome children and their siblings
      in Saudi Arabia.
AB  - OBJECTIVE: To assess the nutritional status and prevalence of obesity among
      children with Down syndrome (DS). METHODS: The study group comprised pre-pubertal
      children, with clinically and cytogenetically proven DS. Healthy siblings,
      closest in age to the DS children, were used as a control group. Body weight,
      height, body mass index (BMI), triceps skinfold thickness (TSFT), and macro- and
      micronutrient intakes were measured in both groups. The study was conducted in
      Riyadh, Kingdom of Saudi Arabia, between February and May 2011. RESULTS: Children
      with DS were shorter than their siblings, but had comparable weights. The DS
      children had higher BMIs and higher TSFTs, compared with their siblings. The
      prevalence of overweight and obesity differed significantly between the DS and
      control groups. The DS children had significantly lower intakes of fat, protein,
      retinol, riboflavin, and potassium compared with their siblings. CONCLUSION:
      Obesity appears to be a prominent feature among Saudi DS children.

PMID- 23147881
TI  - Admission criteria to Saudi medical schools.  Which is the best predictor for
      successful achievement?
AB  - OBJECTIVE: To assess the relationship between current pre-admission criteria and
      medical student's grade point average (GPA) at the end of year 6 in 3 medical
      schools in the Kingdom of Saudi Arabia. METHODS: We conducted this observational
      analytical study at 3 government medical schools in the Kingdom of Saudi Arabia
      between January 2011 and February 2012. High school grades, achievement test
      (Tahsili test) scores, aptitude test (Qudraat tests) scores, Mathematics, and
      English grades in the high school were used to predict medical student's GPA at
      the end of year 6. The criterion variable was student's cumulative GPA at the end
      of year 6. Correlation between pre-admission variables and GPA was calculated
      using Pearson's correlation, and multiple regression analyses. The Institutional
      review board and ethical committee at Taif Medical College approved the study.
      RESULTS: We included 727 students in this study from the chosen medical schools.
      A significant positive correlation was observed among all pre-admission variables
      and GPA. Inclusion of all 5 sets in multiple regression analyses revealed that
      the achievement test, English grade in the high school, high school grade and
      aptitude test (Qudraat tests) were statistically predictive of GPA. A 20.8%
      variance in the GPA can be accounted for by the pre-admission criteria.
      CONCLUSION: Multiple pre-admission factors predict medical students GPA.
      Achievement test is the most important predictor. High school grades in English
      emerged as an independent predictor. Medical schools should give more attention
      to these predictors during admissions.

PMID- 23147882
TI  - Caroli disease with bilateral severe bullous emphysema.  An unknown component.
AB  - We suspected that the multi-bullous parenchymal disease of our patient could be
      related to Caroli disease (CD) because he had no pulmonary pathology before the
      diagnosis of CD. The CD associated with bilateral multiple bullous emphysema may
      be an unknown component.

PMID- 23147883
TI  - Malignant spiradenoma/cylindroma of the vulva.
AB  - Malignant spiradenoma/cylindroma of the vulva is an extremely rare adnexal tumor.
      We report the clinicopathological features of a 58-year-old woman who presented
      with malignant spiradenoma/cylindroma originating in the vulva and metastasized
      to the inguinal lymph nodes. Surgical excision with adequate margins and lymph
      node dissection was performed. Sections from the case were stained with Periodic
      Acid Schiff stain before and after diastase. Immunohistochemical study of the
      case using antibodies to carcinoembryonic antigen (CEA), epithelial membrane
      antigen (EMA), cytokeratin5/6 (CK 5/6), p63, cytokeratin7 (CK 7), smooth muscle
      actin (SMA), and S100 were performed. Microscopic examination revealed that
      spiradenoma nodules were positive to EMA and CEA. However, the cylindroma lobules
      showed strong immunoreactivity to p63 and CK5/6, whereas both tumor components
      were negative to S100, SMA, and CK7. Malignant spiradenoma/cylindroma is a rare
      tumor with controversial histogenesis that should be considered in the
      differential diagnosis of primary adnexal carcinoma and secondary metastatic
      tumors in the vulva. Further studies on a wider cohort should be encouraged.

PMID- 23147884
TI  - Diagnostic dilemma of primary mucosal leishmaniasis.
AB  - Leishmaniasis is caused by Leishmania protozoa. It is widely present in more than
      88 countries worldwide, resulting in up to 80,000 deaths annually. Leishmaniasis
      occurs as visceral, cutaneous, or mucocutaneous variants. Mucosal involvement can
      occur secondarily to the cutaneous or visceral varieties. However, primary
      mucosal leishmaniasis (PML) occurs without any present or past cutaneous and or
      visceral disease. It is extremely rare, and its diagnosis may present a serious
      challenge. It may be difficult to differentiate it from granulomatous conditions
      like tuberculosis, sarcoidosis, leprosy, fungal infections, Wegener's granuloma,
      and neoplasms. Here, we present a case of PML in Saudi Arabia.

PMID- 23147885
TI  - Comparison of pupil diameter measurement with Lenstar LS 900 and OPD Scan II. Not
      interchangeable devices.

PMID- 23147886
TI  - Research as a requirement in a problem-based learning medical curriculum in Saudi
      Arabia.

PMID- 23147887
TI  - Dermatophagoides in childhood asthma.

PMID- 23147888
TI  - Voltage-driven transport of ions and DNA through nanocapillaries.
AB  - We study the effect of salt concentration on the ionic conductance and
      translocation of single DNA molecules through nanocapillaries made out of quartz
      glass. DNA translocation experiments were performed in aqueous solution for
      concentrations of KCl between 10 mM and 2 M while ion conductance was
      characterized from 1 mM to 2 M KCl concentration. Here, we develop a model for
      the conductance of conical nanocapillaries taking into consideration the surface
      charge of the quartz glass. We demonstrate that the conductance of our
      nanocapillaries shows similar behavior to silicon oxide nanopores at low and high
      KCl concentrations. Finally, we show that DNA translocations in high KCl
      concentrations (400 mM-2 M) cause a reduction in the ionic current. In contrast,
      DNA translocations at low KCl concentrations (10-300 mM) lead to increases in the
      ionic current. Our new results, which until now have not been shown for
      nanocapillaries, can be well understood with an adapted model.

PMID- 23147889
TI  - Bone: Bare bones of glucocorticoid effects on metabolism.

PMID- 23147890
TI  - Physical activity levels in the treatment of juvenile fibromyalgia.
AB  - Physical activity is paramount in the treatment of juvenile fibromyalgia,
      although some interventions use indirect methods to increase activity levels
      rather than address physical dysfunction head-on. New research explores the
      effects of a psychotherapeutic approach on levels of physical activity in
      adolescents with fibromyalgia.

PMID- 23147891
TI  - Osteoarthritis of the spine: the facet joints.
AB  - Osteoarthritis (OA) of the spine involves the facet joints, which are located in
      the posterior aspect of the vertebral column and, in humans, are the only true
      synovial joints between adjacent spinal levels. Facet joint osteoarthritis (FJ
      OA) is widely prevalent in older adults, and is thought to be a common cause of
      back and neck pain. The prevalence of facet-mediated pain in clinical populations
      increases with increasing age, suggesting that FJ OA might have a particularly
      important role in older adults with spinal pain. Nevertheless, to date FJ OA has
      received far less study than other important OA phenotypes such as knee OA, and
      other features of spine pathoanatomy such as degenerative disc disease. This
      Review presents the current state of knowledge of FJ OA, including relevant
      anatomy, biomechanics, epidemiology, and clinical manifestations. We present the
      view that the modern concept of FJ OA is consonant with the concept of OA as a
      failure of the whole joint, and not simply of facet joint cartilage.

PMID- 23147892
TI  - Role of peripheral nerve fibres in acute and chronic inflammation in arthritis.
AB  - The peripheral nervous system takes an active part in inflammatory processes by
      regulating effector cell function and reallocation of energy to the immune
      system. During acute inflammation, rapid neuronal reorganization and change of
      activity takes place. The hallmarks of this process are an increase in systemic
      sympathetic activity, a decrease in systemic parasympathetic activity and loss of
      sympathetic nerve fibres from sites of inflammation concomitant with increased
      innervation with sensory nerve fibres and increased sensory nerve fibre activity.
      On a systemic level, the increase in sympathetic activity (and decrease in
      parasympathetic activity) is necessary to provide enough energy to nourish the
      activated immune system. In locally inflamed tissue, the decrease in sympathetic
      nerve fibre density results in reduced anti-inflammatory signalling and, together
      with neuropeptides released from sensory nerve fibres, promotes local
      inflammation. In acute inflammation, this 'inflammatory configuration' of the
      peripheral nervous system favours the rapid clearance of antigenic threats.
      However, in chronic autoimmune inflammation, these changes of the peripheral
      nervous system lead to an unfavourable situation with ongoing energy reallocation
      and continuous local destruction. As an example of a chronic inflammatory
      condition, we discuss evidence for neuroimmune regulation in autoimmune arthritis
      with a focus on the sympathetic nervous system.

PMID- 23147894
TI  - Anaemia in inflammatory rheumatic diseases.
AB  - Anaemia is frequently observed in patients with inflammatory rheumatic diseases.
      Depending on its severity, anaemia negatively affects cardiovascular performance,
      physical activity and the quality of life of patients. However, anaemia is
      considered to be a symptom of the underlying inflammatory disease and, thus,
      neglected as a complex medical condition that warrants specific diagnosis and
      treatment. Although inflammation-induced alterations in iron homeostasis and
      erythropoiesis have a dominant role in the pathogenesis of this type of anaemia,
      multiple other factors such as chronic blood loss, haemolysis, disease and
      treatment-associated adverse effects or vitamin deficiencies can also take part
      in the development of anaemia. Accordingly, the prevalence of anaemia is
      positively associated with the severity of the underlying disease. This Review
      will summarize epidemiological data on anaemia in inflammatory rheumatic
      diseases, along with a detailed description of underlying pathophysiological
      pathways, available diagnostic tools and practical diagnostic strategies.
      Discussion of established and newly emerging treatment regimens, as well as the
      need for further research in this clinically relevant field, will also be
      included.

PMID- 23147895
TI  - Maintenance of clinical remission in ANCA-associated vasculitis.
AB  - A fundamental change in management of antineutrophil cytoplasmic antibody
      associated vasculitis in the past 10 years is the early focussed use of
      aggressive immunosuppression, using regimens comprised of widely available
      medications. Using a clinical framework to quantify morbidity, we can induce
      remission in most patients within 3-6 months using glucocorticoids plus
      methotrexate, cyclophosphamide or rituximab, with additional plasmapheresis when
      indicated. Difficulty in maintaining remission probably relates to the difference
      between true pathophysiological remission and the absence of clinical,
      serological or radiological evidence of disease activity. For surviving patients,
      the cumulative problems of relapse, burden of disease, or its treatment are
      coupled with pre-existing diseases or new conditions arising since diagnosis.
      Initial early control should reduce subsequent damage, but what effect it will
      have on relapse is not clear. In the absence of a cure, future trials should
      focus on reducing toxicity and comorbidity as well as controlling disease.

PMID- 23147901
TI  - Lupus nephritis: Transatlantic management recommendations compared.

PMID- 23147896
TI  - Duality of fibroblast-like synoviocytes in RA: passive responders and imprinted
      aggressors.
AB  - Rheumatoid arthritis (RA) is characterized by hyperplastic synovial pannus
      tissue, which mediates destruction of cartilage and bone. Fibroblast-like
      synoviocytes (FLS) are a key component of this invasive synovium and have a major
      role in the initiation and perpetuation of destructive joint inflammation. The
      pathogenic potential of FLS in RA stems from their ability to express
      immunomodulating cytokines and mediators as well as a wide array of adhesion
      molecule and matrix-modelling enzymes. FLS can be viewed as 'passive responders'
      to the immunoreactive process in RA, their activated phenotype reflecting the
      proinflammatory milieu. However, FLS from patients with RA also display unique
      aggressive features that are autonomous and vertically transmitted, and these
      cells can behave as primary promoters of inflammation. The molecular bases of
      this 'imprinted aggressor' phenotype are being clarified through genetic and
      epigenetic studies. The dual behaviour of FLS in RA suggests that FLS-directed
      therapies could become a complementary approach to immune-directed therapies in
      this disease. Pathophysiological characteristics of FLS in RA, as well as
      progress in targeting these cells, are reviewed in this manuscript.

PMID- 23147902
TI  - Connective tissue diseases: SLE-associated arthropathy: truly a benign entity?

PMID- 23147899
TI  - Systemic sclerosis--challenges for clinical practice.
AB  - The management of patients with systemic sclerosis (SSc) can be challenging
      because disease-associated damage is often difficult to reverse and curative
      therapies are not yet available. Early identification and appropriate monitoring
      of patients with SSc is, therefore, critical so that active disease can be
      controlled and tissue damage prevented or delayed. However, early diagnosis of
      SSc is often difficult because the early clinical stages of the disease can be
      very similar to that of other autoimmune conditions. Screening for major organ
      manifestations of SSc, particularly interstitial lung disease, pulmonary
      hypertension, renal involvement and cardiac disease is a priority because
      involvement of these organs is associated with shorter life expectancies and
      early intervention might prevent disease progression. The prevention and
      management of digital ischaemia is also important as appropriate therapy often
      prevents substantial morbidity and functional loss. Treating gastrointestinal
      dysmotility can usually be managed using proton pump inhibitors and promotility
      agents, although in severe cases total parenteral nutrition is required.
      Calcinosis in patients with SSc is another common challenge that requires
      appropriate disease management and pain control. Each of these topics, which are
      relevant to both physicians and patients with SSc, are reviewed in further detail
      herein.

PMID- 23147905
TI  - Connective tissue diseases: NET loss implicates Nox2 in SLE.

PMID- 23147904
TI  - Paediatric rheumatology: RCT of adalimumab supports anti-TNF therapy for juvenile
      onset ankylosing spondylitis.

PMID- 23147903
TI  - Coagulation and the fibrin network in rheumatic disease: a role beyond
      haemostasis.
AB  - Activation of the immune system has been increasingly recognised to be associated
      with procoagulatory status in patients with inflammatory rheumatic disease.
      Changes in endothelial cell and platelet activation, blood flow, expression and
      activity of different coagulation factors, and impaired fibrinolysis serve as
      pathophysiological basis for enhanced risk of venous thromboembolism in
      inflammatory rheumatic diseases, such as rheumatoid arthritis (RA), connective
      tissue diseases and vasculitides. Recent studies identifying mechanisms for a
      functional role of coagulation factors beyond haemostasis have provided examples
      of interesting links between the coagulation system and innate immune activation.
      Furthermore, citrullinated fibrinogen is an important and early autoantigen in
      patients with RA carrying the HLA-DRbeta1 shared epitope allele, which
      demonstrates an adaptive immune response to a coagulation factor in an
      inflammatory rheumatic disease. Additional studies have provided strong evidence
      that a multitude of different components of the haemostatic system (such as
      thrombin, fibrinogen, coagulation factor XIII and factors of the fibrinolytic
      system) are relevant mediators of inflammatory processes as well as of
      inflammatory control. Understanding the interactions between coagulation and the
      immune system in inflammatory rheumatic diseases will not only improve our
      knowledge of disease mechanisms, but could also permit the development of
      innovative therapeutic interventions.

PMID- 23147906
TI  - Plant-based modulation of Toll-like receptors: an emerging therapeutic model.
AB  - Plant-based extracts present a large source of natural immune modulators, many of
      which have been used in traditional medicine for centuries. Recent research
      efforts have identified plant extracts as potential modulators of Toll-like
      receptors (TLRs), the first responders in immunological defenses in normal and
      disease conditions. This review aims to provide a comprehensive discussion of the
      modulatory effects of plant-based extracts on TLR expression, signaling, and
      activation. We organized the review by extraction solvent and plant part showing
      how they impacted the TLRs. The phytochemical components of the extracts
      discovered to enable these effects are diverse and vary based on the plant part.
      The role of the extraction solvent and differences between the different
      phytochemical components, such as phenolics and polysaccharides, are discussed.
      Plant extracts hold promising treatments for controlling inflammation and,
      conversely, for stimulating the immune response. Further research is needed to
      identify bioactive components of the extracts, mechanisms of their action, and in
      vivo pharmacological effects using appropriate disease models to ultimately adapt
      the findings for clinical use.

PMID- 23147907
TI  - Controlling the diffusion profile of electroactive species for selective anodic
      stripping voltammetry of cadmium at boron-doped diamond electrodes.
AB  - Selective anodic stripping voltammetry of trace metal ions in a mixture solution
      with another interfering metal was developed based on Fick's law concerning the
      diffusion profile of interfering metals at the electrode surface after
      electrolysis treatment. A boron-doped diamond film was used as the sensing
      electrode, while a perforated carbon sheet was used for the interference
      depleting electrode. The influence of the electrode distance and the time of
      electrolysis on the formation of the diffusion profile was studied. As a working
      model, the detection of cadmium with copper interference was investigated. The
      advantage of the method in comparison to general electrolysis was also discussed.
      The method offers a new perspective for improving the selective detection of
      metal ions by analyzing the diffusion profiles of the interfering species at the
      surface of electrodes.

PMID- 23147908
TI  - A mechanochemically synthesised solid solution enables engineering of the
      sorption properties of a Werner clathrate.
AB  - Mechanochemical synthesis has been used to obtain two Werner complexes and their
      solid solution that could not be obtained by conventional "wet" chemistry;
      remarkably, despite the structural and chemical similarity, the solid solution
      exhibits sorption properties that differ from those of the pure compounds.

PMID- 23147909
TI  - In vitro localization of human neural stem cell neurogenesis by engineered FGF-2
      gradients.
AB  - The development of effective stem cell-based therapies for treating brain
      disorders is keenly dependent upon an understanding of how to generate specific
      neural cell types and organize them into functional, higher-order tissues
      analogous to those of the cerebral cortex. Studies of cortical development have
      revealed that the proper formation of the human cerebral cortex results from
      specific intercellular interactions and soluble signaling between the highly
      proliferative region occupied by dividing neural stem cells and an adjacent
      region of active neurogenesis and neural migration. However, the factors
      responsible for establishing this key asymmetrical proliferative-neurogenic
      architecture are not entirely known. Fibroblast growth factor 2 (FGF-2) is
      observed in a ventricular-pial gradient during in vivo development and has been
      previously shown to have effects on both human neural stem cell (hNSC)
      proliferation and neurogenesis. Here we have adapted a microfluidic approach for
      creating stable concentration gradients in 3D hydrogels to explore whether FGF-2
      gradients can establish defined regions of proliferation and neurogenesis in hNSC
      cultures. Exponential but not linear FGF-2 gradients between 0-2 ng mL(-1) were
      able to preferentially boost the percentage of TuJ1(+) neurons in the low
      concentration regions of the gradient and at levels significantly higher than in
      non-gradient controls. However, no gradient-dependent localization was observed
      for dividing hNSCs or hNSC-derived intermediate progenitors. These data suggest
      that exponential FGF2 gradients are useful for generating asymmetric neuron
      cultures, but require contributions from other factors to recapitulate the highly
      proliferative ventricular zone niche. The relevance of the findings of this study
      to in vivo cortical development must be more cautiously stated given the
      artifactual nature of hNSCs and the inability of any in vitro system to fully
      recapitulate the chemical complexity of the developing cortex. However, it is
      quite possible that exponential FGF2 gradients are employed in vivo to establish
      or maintain an asymmetric distribution of neurons in the ventricular-pial axis of
      the developing cerebral cortex.

PMID- 23147910
TI  - Travel and transplantation:  travel-related diseases in transplant recipients.
AB  - PURPOSE OF REVIEW: Travel-related diseases may be seen in transplant recipients
      after travel, after transplant tourism, and via transmission from blood and organ
      donors, augmented by recent increases in travel, migration, and globalization.
      Such infections include tuberculosis, Plasmodium (malaria), Babesia, Trypanosoma
      cruzi (Chagas disease), Strongyloides, Coccidioides, Histoplasma, Leishmania,
      Brucella, HTLV, dengue, among numerous others. RECENT FINDINGS: Review of cohorts
      of transplant recipients show that they tend to have minimal or suboptimal
      preparation prior to travel, with limited pretravel vaccination, medications, and
      education, which poses a greatly increased risk of travel-related infections and
      complications. The epidemiology of such travel-related infections in transplant
      recipients, along with methods for prevention, including vaccines,
      chemoprophylaxis, and education may help SOT recipients avoid travel-related
      infections, and are discussed in this review. SUMMARY: Optimizing the
      understanding of the risk of tropical, geographically restricted, and other
      unusual or unexpected, travel-related infections will enhance the safety of
      vulnerable transplant recipients from potentially life-threatening infections.

PMID- 23147911
TI  - Current world literature.

PMID- 23147913
TI  - Wells' syndrome associated with chronic myeloid leukaemia.

PMID- 23147914
TI  - Are fear avoidance beliefs associated with abdominal muscle activation outcome
      for patients with low back pain?
AB  - BACKGROUND AND PURPOSE: Activation of transversus abdominis and fear avoidance
      beliefs have both been related to low back pain (LBP). This exploratory study
      aims to investigate associations between fear avoidance beliefs at baseline and
      deep abdominal muscle activation after an 8-week period of supervised exercises
      for chronic LBP. METHODS: A cohort of patients with chronic non-specific LBP (N =
      108) enrolled in a clinical trial was studied longitudinally. Fear avoidance
      beliefs for physical activity and work were measured before intervention.
      Activation in transversus abdominis and obliquus internus abdominis during
      abdominal drawing-in manoeuvre and rapid arm flexion was measured by ultrasound
      before and after intervention. Associations between baseline fear avoidance
      beliefs and deep abdominal muscle activation after exercises were analysed with
      multiple linear regression methods. RESULTS: High fear avoidance beliefs for
      physical activity (>=16 on the subscale) were negatively associated with
      transversus abdominis slide after the intervention period, beta = -4.92 (-8.40 to
      -1.45). There were no associations between fear avoidance beliefs for physical
      activity and abdominal muscle onset, transversus abdominis or obliquus internus
      contraction ratio. Fear avoidance beliefs for work were not associated with any
      of the muscle activation parameters. CONCLUSION: This study suggests that there
      is some negative association between fear avoidance beliefs for physical activity
      before intervention and transversus abdominis recruitment measured by lateral
      slide after intervention. No other significant associations between fear
      avoidance beliefs and abdominal muscle activation were found. We cannot exclude
      random findings, meaning that the results should be considered hypothesis
      generating for further investigations.

PMID- 23147915
TI  - Comparison of drug concentrations measured in roadside surveys and in seriously
      injured drivers in Belgium.
AB  - The objective of this paper is to compare concentrations of alcohol, illicit, and
      medicinal drugs in seriously injured drivers and drivers selected randomly at the
      roadside. Blood samples were analyzed for alcohol, 17 medicinal drugs and 8
      illicit psychoactive substances and/or their metabolites by ultra performance
      liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) and gas
      chromatography mass spectrometry (GC-MS) in injured drivers admitted to the
      emergency departments of five hospitals in Belgium between January 2008 and May
      2010 and in drivers randomly selected between January 2008 and September 2009.
      Three hundred and seventy-seven seriously injured drivers and 2750 roadside
      respondents were selected. In the roadside survey, out of the 203 concentrations
      above DRUID (Driving Under the Influence of Drugs, Alcohol and Medicines) cut
      offs for medicinal drugs, 51% were in the therapeutic range, 46%
      infratherapeutic, and 2.5% supratherapeutic. In the seriously injured drivers,
      out of the 78 concentrations above DRUID cut-offs for medicinal drugs, these
      percentages were respectively 63%, 33%, and 4%. Significant differences were
      found in the distribution of concentrations for opioids, benzodiazepines, and Z
      drugs. For the latter, while in the seriously injured drivers study most
      concentrations were therapeutic, in the roadside survey most were
      infratherapeutic. The opposite was observed for the opioids. Eight and 41% of the
      roadside respondents and injured drivers, respectively, had an alcohol
      concentration above 0.1 g/L, with higher concentrations found in the injured
      drivers. For illicit drugs, significant differences were found for amphetamine
      and cocaine, for which respectively lower and higher concentrations were observed
      in the blood samples taken in the roadside survey.

PMID- 23147916
TI  - Resampling the bioconcentration factors data from Japan's chemical substances
      control law database to simulate and evaluate the bioconcentration factors
      derived from minimized aqueous exposure tests.
AB  - Existing standard bioconcentration tests (e.g., the Organization for Economic
      Cooperation and Development [OECD] test guideline 305) require large numbers of
      test animals and resources. The minimized aqueous exposure test is a new approach
      based on the standard bioconcentration test but allows estimation of
      bioconcentration factor (BCF) by minimized sampling of the test fish. The authors
      collected BCF data (298 curves from 155 chemicals, using common carp as test
      species) from Japan's Chemical Substances Control Law database and resampled the
      data to simulate the calculation of BCF that would be obtained if studies had
      been designed to obtain kinetic BCF derived from minimized aqueous exposure tests
      (BCF(km)). The correlation was high (r(2)  = 0.967) between BCF derived from
      standard bioconcentration tests (BCF(full)) and BCF(km). The average value of the
      BCF(full) to BCF(km) ratio (BCF(full):BCF(km)) was 1.04 and ranged from 0.54 to
      1.93, the 5th and 95th percentiles being 0.74 and 1.45, respectively. The results
      based on the 5th and 95th percentiles of the BCF(full):BCF(km) ratio suggest that
      BCF(full) 2,000 corresponds to BCF(km) 1,400 to 2,700, whereas BCF(full) 5,000
      corresponds to BCF(km) 3,400 to 6,800. The authors also emphasize that the
      standard bioconcentration test should be performed when the resulting BCF(km) is
      in the region of regulatory concern.

PMID- 23147917
TI  - The evolution of technological strategies in the prevention of dialysis water
      pollution: sixteen years' experience.
AB  - AIM: This report attempts to illustrate the positive impact on the quality of
      dialysis water produced over a 16-year period through the progressive
      optimization of technological procedures. METHODS: Fundamental steps included the
      following: elimination of polyvinyl chloride (PVC), periodical controls,
      introduction of stainless steel and/or polyethylene polymer and substitution of
      single-pass reverse osmosis (SRO) with double-pass reverse osmosis (DRO). Daily
      overnight automatic thermal disinfection of distribution piping rings represented
      the final step. RESULTS: A dramatic improvement was observed in 645 water samples
      obtained from distribution piping. The measures applied resulted in a significant
      improvement of water quality, featuring levels of colony-forming units per
      milliliter ranging from 247.4 +/- 393.7 in the presence of PVC and SRO to 14.1 +/
      28.0 with stainless steel and DRO and 2.8 +/- 3.2 with cross-linked polyethylene
      thermoplastic polymer and DRO (p < 0.01). CONCLUSIONS: Dialysis water should be
      viewed by nephrologists as a medicinal product, and every effort should be made
      to ensure a high-quality liquid.

PMID- 23147919
TI  - Prostate cancer: epidemiologic studies and changing clinical practice.

PMID- 23147921
TI  - Transplantation: hydrogen sulphide reduces warm renal ischaemic injury.

PMID- 23147922
TI  - Clinical trials: mirabegron for treating OAB.

PMID- 23147918
TI  - Toward detection of DNA-bound proteins using solid-state nanopores: insights from
      computer simulations.
AB  - Through all-atom molecular dynamics simulations, we explore the use of nanopores
      in thin synthetic membranes for detection and identification of DNA binding
      proteins. Reproducing the setup of a typical experiment, we simulate electric
      field driven transport of DNA-bound proteins through nanopores smaller in
      diameter than the proteins. As model systems, we use restriction enzymes EcoRI
      and BamHI specifically and nonspecifically bound to a fragment of dsDNA, and
      streptavidin and NeutrAvidin proteins bound to dsDNA and ssDNA via a biotin
      linker. Our simulations elucidate the molecular mechanics of nanopore-induced
      rupture of a protein-DNA complex, the effective force applied to the DNA-protein
      bond by the electrophoretic force in a nanopore, and the role of DNA-surface
      interactions in the rupture process. We evaluate the ability of the nanopore
      ionic current and the local electrostatic potential measured by an embedded
      electrode to report capture of DNA, capture of a DNA-bound protein, and rupture
      of the DNA-protein bond. We find that changes in the strain on dsDNA can reveal
      the rupture of a protein-DNA complex by altering both the nanopore ionic current
      and the potential of the embedded electrode. Based on the results of our
      simulations, we suggest a new method for detection of DNA binding proteins that
      utilizes peeling of a nicked double strand under the electrophoretic force in a
      nanopore.

PMID- 23147923
TI  - Prostate cancer: two whole-blood RNA expression signatures for aggressive CRPC.

PMID- 23147926
TI  - Kidney cancer: CRM1-a novel drug target for renal cell carcinoma?

PMID- 23147924
TI  - Prostate cancer: Time for active surveillance of intermediate-risk disease?

PMID- 23147928
TI  - Paediatric urology: scoring system for testicular torsion.

PMID- 23147929
TI  - Paediatrics: understanding pubertal precocity-are kids growing up faster?

PMID- 23147931
TI  - Male factor infertility: inflammasome might contribute to impaired fertility of
      men with spinal cord injury.

PMID- 23147933
TI  - Sexual dysfunction: rodent models of diabetic ED.

PMID- 23147930
TI  - Effects of posterior urethral valves on long-term bladder and sexual function.
AB  - Bladder function is often compromised in juvenile patients with posterior
      urethral valves (PUV). In infancy, such abnormal bladder function is
      characterized by low compliance or overactivity, but later in life the bladder
      tends to become oversized and empties poorly. Polyuria, which is often associated
      with renal failure as well as secondary changes in the bladder neck, also has an
      effect on bladder function. Perhaps as a consequence of these contributing
      factors, toilet training is often delayed in children with PUV. Adults who were
      treated for PUV as a child tend to experience lower urinary tract symptoms at a
      rate twofold to threefold higher than healthy men. Furthermore, these adult
      patients with PUV might have risk factors for sexual and fertility dysfunctions
      later in life, such as cryptorchidism, renal failure and abnormal posterior
      urethra. However, despite the high incidence of these risk factors, sexual
      function and fertility seems to be normal in most patients.

PMID- 23147937
TI  - Prostate cancer: challenges in selecting the optimal therapy.

PMID- 23147938
TI  - Incontinence: sling when you're winning-determining the value of repeat surgery
      after failed midurethral sling.

PMID- 23147941
TI  - Homicidal behaviour among people with avoidant, dependent and obsessive
      compulsive (cluster C) personality disorder.
AB  - BACKGROUND: Despite a growing forensic psychiatry literature, no previous study
      has examined in detail homicidal behaviour among offenders with cluster C
      personality disorders - the avoidant, dependent or obsessional personality
      disorders. AIMS: This study aims to compare homicide offenders with cluster C
      personality disorders with those with other personality disorders on criminal
      history, offender-victim relationship and post-offence reaction variables.
      METHODS: The sample was drawn from all Finnish homicide cases of 1996-2004 for
      whom a forensic psychiatric evaluation had been conducted. Data were extracted
      from forensic psychiatric and crime reports. RESULTS: In a nationwide sample of
      593 homicide offenders, 21 had at least one cluster C personality disorder. These
      offenders had significantly shorter criminal histories than the others. Offender
      victim relationship did not differ between the groups, but confession to the
      crime and feelings of remorse were more common among people with cluster C
      disorders. In addition, compared with other personality disorder clusters, co
      morbid depression was more common. CONCLUSIONS: Cluster C personality disorders
      are rare, but not nonexistent, among homicide offenders. Observed differences in
      their backgrounds and post-offence behaviours indicate that they may have special
      needs.

PMID- 23147943
TI  - Cadernos de Saude Publica/Reports in Public Health: a new phase.

PMID- 23147942
TI  - A facile protocol for the immobilisation of vesicles, virus particles, bacteria,
      and yeast cells.
AB  - Immobilisation of liposomes and cells is often a prerequisite for long-term
      observations. The most common immobilisation approaches rely on surface
      modifications, encapsulation in porous materials or trapping in microfluidic
      channels by means of hurdle-like structures. While these approaches are useful
      for larger mammalian cells, the immobilisation of smaller organisms like bacteria
      and yeast or membrane model systems such as liposomes typically requires
      modification of their outer membrane to ensure that they are stably arrested at a
      defined position. Here, we present a protocol to immobilise biological objects,
      which can interact with hydrophobic cholesterol. A water-soluble molecule
      (cholesterol-PEG-biotin) is used as a linker, which can bind via avidin to
      biotinylated BSA (bBSA) previously absorbed on a glass surface. For better
      visualization, bBSA is arranged in a dot pattern by means of microcontact
      printing, and a microfluidic channel is used for sample supply. We show that our
      approach can be used to successfully immobilise artificial liposomes of different
      sizes, native (cell-derived) vesicles, vaccinia virions, Saccharomyces cerevisiae
      and Escherichia coli, simply by flushing the objects through the channel. Under
      these conditions, small liposomes and biological objects are stably arrested at
      high flow rates, while larger cells and liposomes can be released again by
      application of high shear stress. This protocol can be applied for long-term
      studies where fluids must be changed repeatedly, for measuring fast kinetics
      where rapid fluid exchange is essential, and to study the effects of shear
      stress.

PMID- 23147944
TI  - [The morality of nanotechnology].
AB  - Nanotechnology is a set of knowledge, techniques, and practices in studying and
      exploring new properties of materials that arise when manipulated at the atomic
      and molecular levels. The technical possibility of organizing and controlling
      matter at the smallest dimensions and units can result in profound changes in
      industrial production processes and have significant moral impacts on human
      relations, organization of the current social order, and even life as a
      phenomenon. However, moral reflection on nanotechnology has been criticized over
      the assertion that nanotechnology fails to raise any new ethical issue, for
      example. The current article discusses the limits of this claim by presenting two
      aspects that distinguish between nanotechnology and earlier biotechnoscientific
      advances in terms of their ethical implications: (a) uncertainty as an epistemic
      characteristic and (b) the threat to the current symbolic character of DNA as the
      "code of life".

PMID- 23147945
TI  - [Socioeconomic and demographic indicators associated with functional disability
      in the elderly].
AB  - This study analyzed the prevalence of functional disability in the elderly and
      its association with socioeconomic and demographic factors. This was a population
      based cross-sectional study with a sample of 631 elders (>= 60 years). The Katz
      index and Lawton scale, respectively, were used to evaluate basic and
      instrumental activities of daily living. Demographic and socioeconomic variables
      were analyzed. Numerical variables were tested with the Student t test and non
      numerical ones with the chi-square test. The odds of functional disability were
      measured by logistic regression. Prevalence rates of functional disability for
      basic and instrumental activities of daily living were 15.5% and 26.1%,
      respectively. Instrumental activities presented more variables significantly
      associated with the outcome in the final logistic regression model. Prevalence of
      functional disability was not higher than described in the Brazilian literature.
      An important association was found between the outcome and independent variables.

PMID- 23147946
TI  - Prevention of cervical cancer in women with ASCUS in the Brazilian Unified
      National Health System: cost-effectiveness of the molecular biology method for
      HPV detection.
AB  - This study aimed to assess the performance of PCR as a means of detecting HPV
      16/18 compared to the single probe-based PCR for detecting high-risk HPV, and
      evaluate these methods for detecting cervical intraepithelial neoplasia (CIN) in
      follow-ups for ASCUS testing. It also compares the costs of cytology, PCR
      methods, colposcopy and biopsy in the Brazilian Unified National Health System.
      Of the 81 patients with ASCUS, 41 (50.6%) tested positive for HPV 16/18 in PCR
      testing and 47 (58.02%) tested positive for high-risk HPV with single probe-based
      PCR testing. The negative predictive value was 93.75% for HPV 16/18 PCR and 100%
      for single probe-based PCR in cases that progressed to high-grade CIN. The annual
      costs of patient referral were the following: R$2,144.52 for referral of patients
      with ASCUS cytology for colposcopy; R$6,307.44 for referral of patients with
      ASCUS cytology and PCR positive for HPV 16/18 or colposcopy; R$3,691.80 for
      referral of patients with ASCUS cytology with single probe-based PCR positive for
      high-risk HPV. Therefore, cost per user can be reduced by performing single probe
      based PCR for high-risk HPV on patients with ASCUS.

PMID- 23147947
TI  - Waist circumference and waist circumference to height ratios of Kaingang
      indigenous adolescents from the State of Rio Grande do Sul, Brazil.
AB  - The aim of this study was to describe the distribution of waist circumference
      (WC) and WC to height (WCTH) values among Kaingang indigenous adolescents in
      order to estimate the prevalence of high WCTH values and evaluate the correlation
      between WC and WCTH and body mass index (BMI)-for-age. A total of 1,803
      indigenous adolescents were evaluated using a school-based cross-sectional study.
      WCTH values > 0.5 were considered high. Higher mean WC and WCTH values were
      observed for girls in all age categories. WCTH values > 0.5 were observed in
      25.68% of the overall sample of adolescents. Mean WC and WCTH values were
      significantly higher for adolescents with BMI/age z-scores > 2 than for those
      with normal z-scores. The correlation coefficients of WC and WCTH for BMI/age
      were r = 0.68 and 0.76, respectively, for boys, and r = 0.79 and 0.80,
      respectively, for girls. This study highlights elevated mean WC and WCTH values
      and high prevalence of abdominal obesity among Kaingang indigenous adolescents.

PMID- 23147948
TI  - [The metrology of uncertainty: a study of vital statistics from Chile and
      Brazil].
AB  - This paper addresses the issue of uncertainty in the measurements used in public
      health analysis and decision-making. The Shannon-Wiener entropy measure was
      adapted to express the uncertainty contained in counting causes of death in
      official vital statistics from Chile. Based on the findings, the authors conclude
      that metrological requirements in public health are as important as the
      measurements themselves. The study also considers and argues for the existence of
      uncertainty associated with the statistics' performative properties, both by the
      way the data are structured as a sort of syntax of reality and by exclusion of
      what remains beyond the quantitative modeling used in each case. Following the
      legacy of pragmatic thinking and using conceptual tools from the sociology of
      translation, the authors emphasize that by taking uncertainty into account,
      public health can contribute to a discussion on the relationship between
      technology, democracy, and formation of a participatory public.

PMID- 23147949
TI  - [Family Health Support Centers: challenges and opportunities from the perspective
      of primary care professionals in the city of Sao Paulo, Brazil].
AB  - Family Health Support Centers (NASF) were created in Brazil to increase the case
      resolution capacity of primary healthcare. Prior to their implementation in the
      West Side of the city of Sao Paulo, Brazil, a series of workshops were held for
      primary healthcare professionals to prepare a proposal for such centers.
      Hermeneutic analysis was used to study the transcribed material. The thematic
      categories were: role, constitution, and functioning of the NASF, relationship
      with family health teams, and interdisciplinarity. The participants' expected the
      NASF to be an empowering device for comprehensiveness of care, intervening in an
      existing culture of unnecessary referrals while fostering linkage with other
      levels of care. The participants also expected the NASF to contribute to the
      discussion on health professionals' training and stimulating reflection with
      policymakers on health indicators based exclusively on the number of
      consultations. These indicators fail to reflect the impact on the services'
      activities and the quality of care offered to the population in the coverage
      area.

PMID- 23147950
TI  - [Hemoglobin level in older adults and the association with nutritional status and
      use of health services: the Bambui Project].
AB  - This study aimed to describe the prevalence of anemia and to evaluate the
      association between hemoglobin (Hb) level and indicators of nutritional status
      and health services utilization in an elderly population (>= 60 years). Of the
      1,742 older adults in the baseline of the Bambui cohort, 1,441 (82.7%) were
      included. The dependent variable was Hb level, and the independent variables were
      number of hospitalizations and physician visits in the previous 12 months, body
      mass index (BMI), and serum albumin. Multivariate linear regression was
      performed, stratified by gender and adjusted for confounding factors. Prevalence
      of anemia was low (4.5%), with no difference by gender, and higher in the oldest
      old (10.2%). Low Hb level was associated with more physician visits and lower
      serum albumin and BMI in both men and women, suggesting a complex cycle between
      low Hb level, malnutrition, and medical care that should be considered when
      structuring health programs for the elderly.

PMID- 23147951
TI  - [Uses and influence of health evaluation in two studies on the Brazilian National
      Dengue Fever Control Program].
AB  - Evaluation aims to provide information, promote improvement in programs, and
      determine the merit and value of the object of evaluation. However, the challenge
      for evaluators is not only to promote, but also to document the usefulness of
      studies. Given this challenge, the article aimed to systematize the uses and
      influence of the process and findings in two evaluations on Brazilian National
      Dengue Fever Control Program, for decision-making by the respective public health
      administrators and professionals. Based on a theoretical analytical model, an
      exploratory study was performed with documental analysis for identification of
      events and registrations in the evaluations and their circulation in terms of
      possible uses and influence, from 2007 to 2010. Favorable factors for the use of
      evaluations were the mode of production of contextual knowledge and definition of
      evaluations with a focus on utility. The results, indicating greater instrumental
      use and immediate process and collective use may indicate the studies' pertinence
      to stakeholders and their usefulness to program management at different levels in
      the health system.

PMID- 23147952
TI  - [Prenatal care in public and private health services: a population-based survey
      in Rio Grande, Rio Grande do Sul State, Brazil].
AB  - This study aimed to evaluate public and private prenatal care for women in Rio
      Grande, Rio Grande do Sul State, Brazil. Women who gave birth at the two local
      maternity hospitals from January 1 to December 31, 2010, answered a standardized
      questionnaire. The interview sites in the public sector were primary health care
      units with and without the Family Health Strategy (FHS) and outpatient clinics;
      the private sector included clinics operated by health plans and private
      physicians' offices. The chi-square test was used to compare proportions. The
      response rate was 97.2% (2,395 out of 2,464). Among the 23 target variables and
      indicators, seven showed a clear advantage for mothers who had received prenatal
      care under the FHS and six for health plan clinics and private offices. Four
      variables showed virtually universal coverage at all five study sites. Prenatal
      care showed better coverage for pregnant women treated in the private sector.
      Pregnant women treated under the FHS showed similar coverage to that in the
      private sector.

PMID- 23147953
TI  - [Voice disorders related to job stress in teaching: a case-control study].
AB  - This case-control study aimed to test the association between voice disorders and
      job stress among public schoolteachers in Sao Paulo, Brazil. The groups consisted
      of teachers with (n = 165) and without (n = 105) voice-related complaints. Both
      groups answered the questionnaires Conditions of Vocal Production and Job Stress
      Scale. Analysis of cases and controls showed comparable samples, differing only
      by vocal symptoms. There was a statistically significant difference between cases
      and controls in relation to job stress involving high strain (OR = 2.1; 95%CI:
      1.1-3.9), which places high demands combined with low job control. High strain in
      cases in this study represents the highest risk of physical and mental disorders
      for teachers. Loss of voice prevents teachers from continuing in their
      professional role, eliminates their professional identity, and jeopardizes their
      career.

PMID- 23147954
TI  - Cancer incidence in the Western Amazon: population-based estimates in Rio Branco,
      Acre State, Brazil, 2007-2009.
AB  - Cancer incidence rates vary widely in Brazil. The literature on the subject for
      the western Amazon region is scarce. This study aimed to determine cancer
      incidence in the population of Rio Branco, Acre State. A total of 718 new cases
      were recorded during the study period. Among men, the five leading cancer sites
      were prostate (ASR 75.1), stomach (ASR 23.0), lung (ASR 19.1), colon and rectum
      (ASR 9.5), and leukemia (ASR 6.9). Among women, they were breast (ASR 41.5),
      cervix (ASR 41.3), lung (ASR 11.8), colon and rectum (ASR 11.0), and stomach (ASR
      7.7). These indicators reveal that Rio Branco has a cancer incidence pattern that
      overlaps with epidemiological cancer patterns observed in developed and
      developing regions. The results of the study point to the importance of
      implementing a population-based cancer registry - currently nonexistent in Rio
      Branco - as a factor to promote analysis of incident cases of the disease and
      monitoring of its evolution.

PMID- 23147955
TI  - Men's health: a population-based study on social inequalities.
AB  - This study evaluates social inequalities in health according to level of
      schooling in the male population. This was a cross-sectional, population-based
      study with a sample of 449 men ranging from 20 to 59 years of age and living in
      Campinas, Sao Paulo State, Brazil. The chi-square test was used to verify
      associations, and a Poisson regression model was used to estimate crude and
      adjusted prevalence ratios. Men with less schooling showed higher rates of
      alcohol consumption and dependence, smoking, sedentary lifestyle during leisure
      time, and less healthy eating habits, in addition to higher prevalence of bad or
      very bad self-rated health, at least one chronic disease, hypertension, and other
      health problems. No differences were detected between the two schooling strata in
      terms of use of health services, except for dental services. The findings point
      to social inequality in health-related behaviors and in some health status
      indicators. However, possible equity was observed in the use of nearly all types
      of health services.

PMID- 23147956
TI  - [Integrative and complementary health practices: the supply and production of
      care in the Unified National Health System and in selected municipalities in
      Brazil].
AB  - The world of Traditional/Complementary and Alternative Medicine has grown and its
      importance has been emphasized in several studies. In Brazil, the National Policy
      on Integrative and Complementary Practices encourages their inclusion and
      empowerment in primary care. This study attempted to identify the provision of
      services and integrative practices in the Unified National Health System and the
      production of consultations from 2000 to 2011, contrasting the analysis of
      available information in national databases with the primary care data collected
      locally in Campinas (Sao Paulo State), Florianopolis (Santa Catarina State), and
      Recife (Pernambuco State). Analysis of the data revealed a mismatch between
      records in information systems and actual practices in these cities. This
      mismatch is due largely to lack of definition on the scope of what are understood
      as integrative and complementary practices in the Brazilian National Policy,
      thereby posing a major limitation to their measurement and evaluation, since
      current information does not allow adequate recording of such practices.

PMID- 23147957
TI  - [Sedentary leisure time and food consumption among Brazilian adolescents: the
      Brazilian National School-Based Adolescent Health Survey (PeNSE), 2009].
AB  - The objective of this paper was to investigate whether sedentary leisure time was
      associated with increased regular consumption of unhealthy foods, independently
      of socio-demographic indicators and family context. The analysis included 59,809
      students from the Brazilian National School-Based Adolescent Health Survey
      (PeNSE) in 2009. The response variable was sedentary leisure time, defined as
      watching more than two hours of TV daily. The target explanatory variables were
      regular consumption of soft drinks, sweets, cookies, and processed meat. Odds
      ratios (OR) and 95% confidence limits (95%CI) were obtained by multiple logistic
      regression. Prevalence of sedentary leisure time was 65%. Regular consumption of
      unhealthy foods was statistically higher among students reporting sedentary
      leisure time, before and after adjusting for sex, age, skin color, school
      administration (public versus private), household assets index, and household
      composition. The results indicate the need for integrated interventions to
      promote healthy leisure-time activities and healthy eating habits among young
      people.

PMID- 23147958
TI  - [Differences in risk factors for infant mortality in five Brazilian cities: a
      case-control study based on the Mortality Information System and Information
      System on Live Births].
AB  - This study aimed to identify differences in risk factors for infant mortality in
      five cities, one from each region of Brazil. This was a case-control study with
      cases defined as deaths in infants less than one year of age in the Mortality
      Information System (SIM) and Information System on Live Births (SINASC) and
      controls as live born infants recorded in the SINASC database and who had not
      died in the first year. Risk factors were estimated by univariate and
      multivariate analysis, using hierarchical logistic models. The main determinants
      of infant mortality were biological factors (low Apgar score, low birth weight,
      prematurity, and congenital malformations) mediated by socioeconomic factors
      (education, marital status, and race/color) and prenatal care conditions
      (prenatal visits). Despite agreement on the determinants of infant mortality
      among the five cities, some regional differences were observed, expressing infant
      mortality associated with inequalities in socioeconomic conditions and access to
      health services.

PMID- 23147959
TI  - Factors influencing growth and intestinal parasitic infections in preschoolers
      attending philanthropic daycare centers in Salvador, Northeast Region of Brazil.
AB  - Poor growth and intestinal parasitic infections are widespread in disadvantaged
      urban children. This cross-sectional study assessed factors influencing poor
      growth and intestinal parasites in 376 children aged three to six years in
      daycare centers in Salvador, in the Northeast Region of Brazil. Data was obtained
      from seven daycare centers on child weight, height, socio-economic status, health
      and intestinal parasites in stool samples. Prevalence of moderate underweight (< 
      1SD > -2SD), wasting and stunting was 12%, 16% and 6% respectively. Socioeconomic
      status, birth order, and maternal weight were predictors of poor anthropometric
      status. Almost 30% of children were infected with more than one intestinal
      parasite. Helminths (17.8%), notably Trichuris trichiura (12%) and Ascaris
      lumbricoides (10.5%), and protozoan Giardia duodenalis (13%) were the most common
      types of parasites detected. One percent of children had hookworm and
      Cryptosporidium sp. and 25% had non-pathogenic protozoan cysts. Boys from
      families with very low socio-economic status had lower linear growth and
      presented a greater risk of helminth infection. Deworming is considered an
      alternative for reducing the prevalence of intestinal parasitic infections in
      this age group.

PMID- 23147960
TI  - Temporal analysis of the relationship between dengue and meteorological variables
      in the city of Rio de Janeiro, Brazil, 2001-2009.
AB  - Dengue, a reemerging disease, is one of the most important viral diseases
      transmitted by mosquitoes. Climate is considered an important factor in the
      temporal and spatial distribution of vector-transmitted diseases. This study
      examined the effect of seasonal factors and the relationship between climatic
      variables and dengue risk in the city of Rio de Janeiro, Brazil, from 2001 to
      2009. Generalized linear models were used, with Poisson and negative binomial
      distributions. The best fitted model was the one with "minimum temperature" and
      "precipitation", both lagged by one month, controlled for "year". In that model,
      a 1 degrees C increase in a month's minimum temperature led to a 45% increase in
      dengue cases in the following month, while a 10-millimeter rise in precipitation
      led to a 6% increase in dengue cases in the following month. Dengue transmission
      involves many factors: although still not fully understood, climate is a critical
      factor, since it facilitates analysis of the risk of epidemics.

PMID- 23147961
TI  - [Translation and cross-cultural adaptation of the Brazilian version of the
      Hospital Survey on Patient Safety Culture: initial stage].
AB  - Patient safety culture assessment allows hospitals to identify and prospectively
      manage safety issues in work routines. This article aimed to describe the cross
      cultural adaptation of the Hospital Survey on Patient Safety Culture (HSOPSC)
      into Brazilian Portuguese. A universalist approach was adopted to assess
      conceptual, item, and semantic equivalence. The methodology involved the
      following stages: (1) translation of the questionnaire into Portuguese; (2) back
      translation into English; (3) an expert panel to prepare a draft version; and (4)
      assessment of verbal understanding of the draft by a sample of the target
      population. The questionnaire was translated into Portuguese, and the scale's
      final version included 42 items. The target population sample assessed all the
      items as easy to understand. The questionnaire has been translated into
      Portuguese and adapted to the Brazilian hospital context, but it is necessary to
      assess its measurement equivalence, external validity, and reproducibility.

PMID- 23147962
TI  - Changes in cigarette consumption patterns among Brazilian smokers between 1989
      and 2008.
AB  - The assessment of temporal differences in cigarette consumption may help in
      understanding whether a smoking population is becoming more resistant to quitting
      over time. We calculated absolute differences in average cigarette consumption,
      stratified by birth cohort and age group. Data were obtained from random samples
      from two Brazilian national household surveys (1989, N = 12,782; 2008, N =
      6,675). A linear regression model was used to adjust estimates by gender,
      educational level, and place of residence. Birth cohort analysis found that
      average daily cigarette consumption increased for individuals born after 1964 and
      decreased for those born before 1955 (adjusted p-values < 0.001). Age-specific
      analysis found that the remaining smoking population aged 64 years-old or less
      decreased cigarette consumption between 1989 and 2008 (adjusted p-values <
      0.001). Brazil's anti-tobacco policy changes and rapid economic growth may be
      principally related to temporal changes in cigarette consumption for most age
      groups, rather than to a change in the relationship between age and cigarette
      consumption.

PMID- 23147963
TI  - Structure and speciation of chromium ions in chromium doped Fe2O3 catalysts.
AB  - In this paper, we report a detailed characterisation of chromium doped iron oxide
      catalysts using a range of techniques to establish the nature of chromium species
      in the near surface and bulk of iron oxide, high-temperature shift (HTS)
      catalysts. In particular we have employed X-ray absorption spectroscopy Cr K-edge
      near edge and extended fine structure data for comparison with chemical and X-ray
      photoelectron spectroscopy. There was excellent agreement between the techniques
      in terms of identification and quantification of Cr(6+) and Cr(3+) species as a
      function of calcination temperatures between 100 and 500  degrees C.

PMID- 23147964
TI  - The inhibition by levocetirizine and fexofenadine of the histamine-induced wheal
      and flare response in healthy Caucasian and Japanese volunteers.
AB  - This randomized, double-blind, placebo-controlled crossover study compared
      inhibition by one 5 mg dose of levocetirizine with two 60 mg doses of
      fexofenadine separated by 12 h of histamine-induced wheal and flare responses in
      9 Caucasian and 9 Japanese healthy male volunteers. Levocetirizine was more
      inhibitory than fexofenadine on wheal, flare and pruritus (p < 0.005).
      Variability, evaluated from the standard deviation of inhibition, ranged from 14%
      to 23.2% for levocetirizine and 65.4% to 112.4% for fexofenadine. Levocetirizine
      had a faster onset of action (30-90 min versus 2 h), shorter time to maximum
      effect (3-4 versus 3-6 h) and longer duration of action (at least 24 h versus ~12
      h) than fexofenadine. The plasma levels of levocetirizine rose more quickly,
      reached higher levels, were more consistent and decreased slower than those of
      fexofenadine. There were no clinically significant ethnic differences in
      responsiveness to the drugs.

PMID- 23147965
TI  - The use of intravenous palivizumab for treatment of persistent RSV infection in
      children with leukemia.
AB  - Palivizumab is a humanized monoclonal antibody used to decrease the threat of
      respiratory syncytial virus (RSV) infection among children at high risk. There
      are no standard guidelines due to conflicting data on palivizumab's use in the
      treatment of RSV lower respiratory tract infections. Intravenous (IV) palivizumab
      was shown to be well tolerated and associated with decreased mortality in high
      risk children who have RSV disease. However, it did not prevent lower respiratory
      tract infections and did not affect the survival rate of allogeneic stem cell
      transplant recipients who had RSV infection. We present 2 children with acute
      lymphocytic leukemia (ALL) and persistent RSV infection while receiving
      chemotherapy. Patient A is a 4-year-old male with Down syndrome, ALL, and
      persistent RSV infection for at least 3 months. Patient B is a 3-year-old female
      with pre-B cell ALL whose chemotherapy intensification phase was delayed due to a
      month-long RSV infection. RSV infections were determined by using real-time
      polymerase chain reaction assays from nasopharyngeal swabs before IV palivizumab
      therapy; patient A was positive for RSV at 36 cycles and patient B was positive
      for RSV at 29 cycles. RSV infection was cleared in both patients within 72 hours
      after receiving IV palivizumab (patient A: 16 mg/kg; patient B: 15 mg/kg). IV
      palivizumab may be a treatment option for persistent RSV infection among
      immunocompromised patients.

PMID- 23147966
TI  - Fish consumption in infancy and asthma-like symptoms at preschool age.
AB  - OBJECTIVE: To assess whether timing of introduction of fish and the amount of
      fish consumption in infancy were associated with asthmalike symptoms at preschool
      age. METHODS: This study was embedded in the Generation R study (a population
      based birth cohort in Rotterdam, Netherlands). At the age of 12 and 14 months,
      timing of introduction of fish into the infant's diet was assessed. The amount of
      fish consumption at 14 months was assessed by a semiquantitative food frequency
      questionnaire. Presence of asthmalike symptoms in the past year was assessed at
      the child's age of 36 and 48 months. RESULTS: Relative to no introduction in the
      first year of life, introduction between age 6 and 12 months was significantly
      associated with a lower risk of wheezing at 48 months (odds ratio [OR]: 0.64; 95%
      CI: 0.43-0.94). When compared with introduction between 6 and 12 months, no
      introduction in the first year and introduction between 0 and 6 months were
      associated with an increased risk of wheezing at 48 months (OR: 1.57; 95% CI:
      1.07-2.31 and OR: 1.53; 95% CI: 1.07-2.19, respectively). The amount of fish at
      age 14 months was not associated with asthmalike symptoms (P > .15). CONCLUSIONS:
      Introduction of fish between 6 and 12 months but not fish consumption afterward
      is associated with a lower prevalence of wheezing. A window of exposure between
      the age of 6 and 12 months might exist in which fish might be associated with a
      reduced risk of asthma.

PMID- 23147967
TI  - Self-Report of Child Care Directors Regarding Return-to-Care.
AB  - BACKGROUND: The American Academy of Pediatrics (AAP) introduced revised return-to
      care recommendations for mildly ill children in 2009 that were added to national
      standards in 2011. Child care directors' practices in a state without clear
      emphasis on return-to-care guidelines are unknown. We investigated director
      return-to-care practices just before the release of recently revised AAP
      guidelines. METHODS: A telephone survey with 5 vignettes of mild illness (cold
      symptoms, conjunctivitis, vomiting/diarrhea, fever, and ringworm) was
      administered to randomly sampled directors in metropolitan Milwaukee, Wisconsin.
      Directors were asked about return-to-care criteria for each illness. Questions
      for return-to-care criteria were open-ended; multiple responses were allowed.
      Answers were compared with AAP return-to-care recommendations. RESULTS: A total
      of 305 directors participated. Based on director responses to vignettes, the
      percentage of correct responses regarding return-to-child care management
      compared with AAP return-to-care recommendations was low: fever (0%);
      conjunctivitis (0%); diarrhea (1.6%); cold symptoms (12%); ringworm (21%); and
      vomiting (80%). Two illnesses (conjunctivitis and cold symptoms) would require
      the child to have an urgent medical evaluation or treatment not recommended by
      the AAP, as follows: Conjunctivitis-antibiotics for 24 hours (62%), physician
      visit (49%), any antibiotic treatment (6%), and symptom resolution (4%); and Cold
      Symptoms-physician visit (45.6%), antibiotics (10%), and symptom resolution
      (25%). CONCLUSIONS: Directors' self-reported return-to-child care practices
      differed substantially before the release of revised AAP return-to-care
      recommendations. Active adoption of AAP return-to-child care guidelines would
      decrease the need for unnecessary urgent medical evaluation and treatment as well
      as unnecessary exclusion of a child from child care.

PMID- 23147968
TI  - Prevalence of overweight in Dutch children with Down syndrome.
AB  - OBJECTIVE: Prevalence of overweight in children is increasing, causing various
      health problems. This study aims to establish growth references for weight and to
      assess the prevalence rates of overweight and obesity in a nationwide sample of
      Dutch children with Down syndrome (DS), taking into account the influence of
      comorbidity. METHODS: In 2009, longitudinal growth data from Dutch children with
      trisomy 21 who were born after 1982 were retrospectively collected from medical
      records of 25 Dutch regional specialized DS centers. "Healthy" was defined as not
      having concomitant disorders or having only a mild congenital heart defect.
      Weight and BMI references were calculated by using the LMS method, and prevalence
      rates of overweight and obesity by using cutoff values for BMI as defined by the
      International Obesity Task Force. Differences in prevalence rates were tested by
      multilevel logistic regression analyses to adjust for gender and age. RESULTS:
      Growth data of 1596 children with DS were analyzed. Compared with the general
      Dutch population, healthy children with DS were more often overweight (25.5% vs
      13.3% in boys, and 32.0% vs 14.9% in girls) and obese (4.2% vs 1.8%, and 5.1% vs
      2.2%, respectively). Prevalence rates of overweight between DS children with or
      without concomitant disorders did not vary significantly. CONCLUSIONS: Dutch
      children with DS have alarmingly high prevalence rates of overweight and obesity
      during childhood and adolescence. Health care professionals should be aware of
      the risk of overweight and obesity in children with DS to prevent complications.

PMID- 23147969
TI  - Autism after infection, febrile episodes, and antibiotic use during pregnancy: an
      exploratory study.
AB  - OBJECTIVES: Results of animal studies suggest that maternal immune activation
      during pregnancy causes deficiencies in fetal neurodevelopment. Infectious
      disease is the most common path to maternal immune activation during pregnancy.
      The goal of this study was to determine the occurrence of common infections,
      febrile episodes, and use of antibiotics reported by the mother during pregnancy
      and the risk for autism spectrum disorder (ASD) and infantile autism in the
      offspring. METHODS: We used a population-based cohort consisting of 96 736
      children aged 8 to 14 years and born from 1997 to 2003 in Denmark. Information on
      infection, febrile episodes, and use of antibiotics was self-reported through
      telephone interviews during pregnancy and early postpartum. Diagnoses of ASD and
      infantile autism were retrieved from the Danish Psychiatric Central Register; 976
      children (1%) from the cohort were diagnosed with ASD. RESULTS: Overall, we found
      little evidence that various types of mild common infectious diseases or febrile
      episodes during pregnancy were associated with ASD/infantile autism. However, our
      data suggest that maternal influenza infection was associated with a twofold
      increased risk of infantile autism, prolonged episodes of fever caused a
      threefold increased risk of infantile autism, and use of various antibiotics
      during pregnancy were potential risk factors for ASD/infantile autism.
      CONCLUSIONS: Our results do not suggest that mild infections, febrile episodes,
      or use of antibiotics during pregnancy are strong risk factors for ASD/infantile
      autism. The results may be due to multiple testing; the few positive findings are
      potential chance findings.

PMID- 23147970
TI  - Informed choice for newborn blood spot screening in the United Kingdom: a survey
      of parental perceptions.
AB  - OBJECTIVE: In the United Kingdom, newborn blood spot screening proceeds on the
      basis of consent based on an informed choice. However, little is known about
      parent experiences of this process. This study was intended to explore parents'
      understanding of newborn screening and their experience of the consent process
      using a structured survey. METHODS: A mail survey exploring key components of
      consent was sent to parents whose children had been screened in the year before
      the study. A descriptive analysis of responses together with logistic regression
      was performed to identify variables that predicted parental likelihood to agree
      that they had made an informed choice to screening. RESULTS: Most parents
      indicated they understood why the heel prick was done, but only a third
      understood how conditions would be dealt with if found. Almost a third of parents
      reported that they did not feel they had a choice to decline screening, yet >70%
      felt they had made an informed choice. Logistic regression indicated previous
      children, understanding why the heel prick was done, having time to make a
      decision, and feeling they had a choice were significant predictors of feeling an
      informed choice had been made. CONCLUSIONS: The findings support previous studies
      that screening may be seen as a fait accompli. Analyses indicated that allowing
      time to make a decision (eg, by providing information during pregnancy,
      emphasizing the decision-making aspect, and clearly articulating the reasons
      behind screening) may help parents feel that they have made an informed choice.

PMID- 23147971
TI  - Cost-effectiveness of an injury and drowning prevention program in Bangladesh.
AB  - OBJECTIVE: Interventions that mitigate drowning risk in developing countries are
      needed. This study presents the cost-effectiveness of a low-cost, scalable injury
      and drowning prevention program called Prevention of Child Injuries through
      Social-Intervention and Education (PRECISE) in Bangladesh. METHODS: Between 2006
      and 2010, the 2 components of PRECISE (Anchal, which sequestered children in
      creches [n = 18 596 participants], and SwimSafe, which taught children how to
      swim [n = 79421 participants]) were implemented in rural Bangladesh. Mortality
      rates for participants were compared against a matched sample of nonparticipants
      in a retrospective cohort analysis. Effectiveness was calculated via Cox
      proportional hazard analysis. Cost-effectiveness was estimated according to World
      Health Organization-CHOosing Interventions that are Cost Effective guidelines.
      RESULTS: Anchal costs between $50.74 and $60.50 per child per year. SwimSafe
      costs $13.46 per child. For Anchal participants, the relative risk of a drowning
      death was 0.181 (P = .004). The relative risk of all-cause mortality was 0.56 (P
      = .001). For SwimSafe, the relative risk of a drowning death was 0.072 (P <
      .0001). The relative risk of all-cause mortality was 0.750 (P = .024). For
      Anchal, the cost per disability-adjusted life-year (DALY) averted is $812 (95%
      confidence interval: $589?x{2013}$1777). For SwimSafe, the cost per DALY averted
      is $85 ($51?x{2013}$561). Combined, the cost per DALY averted is $362
      ($232?x{2013}$1364). CONCLUSIONS: Based on World Health Organization criteria,
      PRECISE is very cost-effective and should be considered for implementation in
      other areas where drowning is a significant problem.

PMID- 23147972
TI  - Parents smoking in their cars with children present.
AB  - OBJECTIVE: To determine prevalence and factors associated with strictly enforced
      smoke-free car policies among smoking parents. METHODS: As part of a cluster,
      randomized controlled trial addressing parental smoking, exit interviews were
      conducted with parents whose children were seen in 10 control pediatric
      practices. Parents who smoked were asked about smoking behaviors in their car and
      receipt of smoke-free car advice at the visit. Parents were considered to have a
      "strictly enforced smoke-free car policy" if they reported having a smoke-free
      car policy and nobody had smoked in their car within the past 3 months. RESULTS:
      Of 981 smoking parents, 817 (83%) had a car; of these, 795 parents answered
      questions about their car smoking policy. Of these 795 parents, 29% reported
      having a smoke-free car policy, and 24% had a strictly enforced smoke-free car
      policy. Of the 562 parents without a smoke-free car policy, 48% reported that
      smoking occurred with children present. Few parents who smoke (12%) were advised
      to have a smoke-free car. Multivariable logistic regression controlling for
      parent age, gender, education, and race showed that having a younger child and
      smoking <=10 cigarettes per day were associated with having a strictly enforced
      smoke-free car policy. CONCLUSIONS: The majority of smoking parents exposed their
      children to tobacco smoke in cars. Coupled with the finding of low rates of
      pediatricians addressing smoking in cars, this study highlights the need for
      improved pediatric interventions, public health campaigns, and policies regarding
      smoke-free car laws to protect children from tobacco smoke.

PMID- 23147973
TI  - Home safety and low-income urban housing quality.
AB  - OBJECTIVES: Living in substandard housing may be one factor that increases the
      risk of fire and burn injuries in low-income urban environments. The purposes of
      this study are to (1) describe the frequency and characteristics of substandard
      housing in urban homes with young children and (2) explore the hypothesis that
      better housing quality is associated with a greater likelihood of having working
      smoke alarms and safe hot water temperatures. METHODS: A total 246 caregivers of
      children ages 0 to 7 years were recruited from a pediatric emergency department
      and a well-child clinic. In-home observations were completed by using 46 items
      from the Housing and Urban Development's Housing Quality Standards. RESULTS:
      Virtually all homes (99%) failed the housing quality measure. Items with the
      highest failure rates were those related to heating and cooling; walls, ceilings,
      and floors; and sanitation and safety domains. One working smoke alarm was
      observed in 82% of the homes, 42% had 1 on every level, and 62% had safe hot
      water temperatures. For every increase of 1 item in the number of housing quality
      items passed, the odds of having any working smoke alarm increased by 10%, the
      odds of having 1 on every level by 18%, and the odds of having safe hot water
      temperatures by 8%. CONCLUSIONS: Many children may be at heightened risk for fire
      and scald burns by virtue of their home environment. Stronger collaboration
      between housing, health care, and injury prevention professionals is urgently
      needed to maximize opportunities to improve home safety.

PMID- 23147974
TI  - Management of neonates with hyperbilirubinemia: improving timeliness of care
      using a clinical pathway.
AB  - BACKGROUND: Neonatal hyperbilirubinemia is a common reason for neonates to
      present to the emergency department (ED). Although clinical practice guidelines
      provide recommendations for evaluation and therapy, few studies have evaluated
      ways to apply them effectively in the ED setting. The primary objective of this
      study was to compare time to phototherapy in neonates presenting to the ED with
      jaundice before and after implementation of a nursing-initiated clinical pathway.
      Secondary outcomes included time to bilirubin result and ED length of stay in
      neonates. METHODS: We performed a retrospective historical control study
      comparing neonates presenting to the ED with jaundice during 9-month periods
      before and after initiation of the pathway. Charts were abstracted for times of
      assessment and treatment and final disposition. RESULTS: Three hundred neonates
      were included in this study: 149 before and 151 after pathway implementation.
      Median time to phototherapy (historical control: 128 minutes vs postintervention
      group: 52 minutes; P < .001), median time to bilirubin result (157 vs 99; P <
      .001), and median ED length of stay (268 minutes vs 195 minutes; P < .001) were
      shorter for neonates treated after the implementation of the clinical pathway. No
      complications were reported during the study period. CONCLUSIONS: After
      implementation of a clinical pathway for the management of neonates with jaundice
      in the ED, we observed a reduction in time to phototherapy, time to bilirubin
      measurement, and overall length of stay.

PMID- 23147975
TI  - Obesity disparities among elementary-aged children: data from school-based BMI
      surveillance.
AB  - OBJECTIVES: To examine 3-year trends and spatial clustering in the prevalence of
      obesity among elementary-aged children in Pennsylvania. METHODS: Height and
      weight were measured for ~980 000 children between ages 5 and 12 years,
      corresponding to kindergarten through grade 6 in 3 consecutive school years (2006
      2007, 2007-2008, 2008-2009). These data were obtained at the school district
      level and reported to the Pennsylvania Department of Health in response to a
      state mandate requiring public schools to conduct annual surveillance of student
      growth. Analyses at the school district level (n = 501) regarding obesity
      prevalence (BMI >= 95th percentile) according to age and gender were conducted to
      examine associations over time and in relation to population density, geographic
      boundaries, and a calculated family distress index. RESULTS: The mean prevalence
      of obesity remained stable over 3 years at ~17.6% of elementary-aged children.
      However, within the state, significant differences in the prevalence of obesity
      were identified. Schools in the most rural areas had adjusted obesity prevalence
      over 2 percentage points higher than urban schools. Consistent with secular
      findings for the nation in general, students with families living in
      socioeconomic distress exhibited upward trends in obesity risk. CONCLUSIONS:
      School-based surveillance elucidates the disparate risk of obesity for younger
      students living in the most rural areas, a key finding for primarily rural
      states. Preventive interventions are needed to reach the most rural children with
      an emphasis on families where parents are single, are unemployed, have a lower
      income, and lower educational attainment.

PMID- 23147976
TI  - Successful tocilizumab treatment in a child with refractory Takayasu arteritis.
AB  - Takayasu arteritis (TA) in the child remains a therapeutic challenge because
      corticosteroids and conventional immunosuppressive agents are not always safe or
      efficacious. The complex formed by interleukin-6 (IL-6) and soluble IL-6 receptor
      appears to play a pivotal role in the pathogenesis of TA. We describe a favorable
      response to the anti-IL-6 receptor antibody tocilizumab (TCZ) in a child with
      aggressive and refractory TA including an assessment of the proinflammatory
      cytokine profile. A 3-year-old girl with TA consisting of thickening of the
      aortic arch wall, severe obstruction of the supra-aortic branches, and complete
      occlusion of both common carotid arteries failed to respond to corticosteroids,
      methotrexate, tumor necrosis factor alpha blockade, cyclophosphamide, and
      mycophenolate mofetil, and 3 years later, the disease remained active with severe
      manifestations (brain ischemia). The patient underwent percutaneous angioplasty,
      although significant restenosis was soon documented. After a severe relapse, the
      patient started TCZ infusions (8 mg/kg for 2 weeks), and a rapid clinical
      remission was observed, associated with a drastic reduction of inflammatory
      markers and IL-6 levels. Corticosteroids were withdrawn, the patient's weight and
      height improved, and bone mineral density values returned to normal. Two years
      later, TCZ infusions were extended, with no significant side effects. Cerebral
      ischemia resolved, and recanalization of the previously occluded supra-aortic
      branches was performed.

PMID- 23147977
TI  - Expected body weight in adolescents: comparison between weight-for-stature and
      BMI methods.
AB  - OBJECTIVE: To test the hypothesis that the weight-for-stature (WFS) and BMI
      methods are not equivalent in determining expected body weight (EBW) in
      adolescents with eating disorders and to determine the sensitivity, specificity,
      and positive predictive value of each method to detect those <75% EBW. We
      hypothesized that differences in EBW would be greatest at the extremes of height.
      METHODS: EBW was determined for 12 047 individual adolescents aged 12 to 19 years
      by the WFS and BMI methods by utilizing the same National Center for Health
      Statistics data sets. Absolute difference between the 2 methods for each
      individual was calculated and plotted against height by using a generalized
      additive model. The number of individuals whose weights were <75% EBW was
      determined by each method. RESULTS: For girls, EBW was 3.52 +/- 3.13% higher when
      using the WFS method compared with the BMI method. For boys, EBW(WFS) was 3.45 +/
      2.72% higher than EBW(BMI). Among adolescent girls, 65% had EBW(WFS) higher than
      EBW(BMI). By using the EBW(WFS) method as the gold standard, specificity of the
      EBW(BMI) method to detect those <75% EBW was 0.999, but sensitivity was only
      0.329. Absolute differences in EBW were most pronounced at the extremes of
      height. CONCLUSIONS: The WFS and BMI methods are not equivalent in determining
      EBW in adolescents and are not interchangeable. EBW(WFS) was ~3.5% higher than
      EBW(BMI). In adolescents with eating disorders, use of the BMI method will
      underestimate the degree of malnutrition compared with the WFS method. Which
      method better predicts meaningful clinical outcomes remains to be determined.

PMID- 23147978
TI  - A randomized placebo-controlled trial of massage therapy on the immune system of
      preterm infants.
AB  - OBJECTIVES: The aim of this study was to investigate the effects of massage
      therapy (MT) on the immune system of preterm infants. The primary hypothesis was
      that MT compared with sham therapy (control) will enhance the immune system of
      stable premature infants by increasing the proportion of their natural killer
      (NK) cell numbers. METHODS: A randomized placebo-controlled trial of MT versus
      sham therapy (control) was conducted among stable premature infants in the NICU.
      Study intervention was provided 5 days per week until hospital discharge for a
      maximum of 4 weeks. Immunologic evaluations (absolute NK cells, T and B cells, T
      cell subsets, and NK cytotoxicity), weight, number of infections, and length of
      hospital stay were also evaluated. RESULTS: The study enrolled 120 infants (58
      massage; 62 control). At the end of the study, absolute NK cells were not
      different between the 2 groups; however, NK cytotoxicity was higher in the
      massage group, particularly among those who received >=5 consecutive days of
      study intervention compared with control (13.79 vs 10 lytic units, respectively;
      P = .04). Infants in the massage group were heavier at end of study and had
      greater daily weight gain compared with those in the control group; other
      immunologic parameters, number of infections, and length of stay were not
      different between the 2 groups. CONCLUSIONS: In this study, MT administered to
      stable preterm infants was associated with higher NK cytotoxicity and more daily
      weight gain. MT may improve the overall outcome of these infants. Larger studies
      are needed.

PMID- 23147979
TI  - Timing of the introduction of complementary foods in infancy: a randomized
      controlled trial.
AB  - OBJECTIVE: To increase knowledge on iron status and growth during the first 6
      months of life. We hypothesized that iron status would be better in infants who
      received complementary foods in addition to breast milk compared with those
      exclusively breastfed. METHODS: One hundred nineteen healthy term (>=37 weeks)
      singleton infants were randomly assigned to receive either complementary foods in
      addition to breast milk from age 4 months (CF) or to exclusive breastfeeding for
      6 months (EBF). Dietary data were collected by 3-day weighed food records, and
      data on iron status and growth were also collected. RESULTS: One hundred infants
      (84%) completed the trial. Infants in the CF group had higher mean serum ferritin
      levels at 6 months (P = .02), which remained significant when adjusted for
      baseline characteristics. No difference was seen between groups in iron
      deficiency anemia, iron deficiency, or iron depletion. The average daily energy
      intake from complementary foods of 5-month-olds in the CF group was 36.8 kJ per
      kg body weight. Infants in both groups grew at the same rate between 4 and 6
      months of age. CONCLUSIONS: In a high-income country, adding a small amount of
      complementary food in addition to breast milk to infants' diets from 4 months of
      age does not affect growth rate between 4 and 6 months, but has a small and
      positive effect on iron status at 6 months. The biological importance of this
      finding remains to be determined.

PMID- 23147980
TI  - Hypothalamic-pituitary-adrenal axis suppression in asthmatic school children.
AB  - BACKGROUND AND OBJECTIVE: Hypothalamic-pituitary-adrenal axis suppression (HPAS)
      when treating children with corticosteroids is thought to be rare. Our objective
      was to determine the prevalence of and predictive factors for various degrees of
      HPAS. METHODS: Clinical features of HPAS, doses, adherence, asthma score, and
      lung functions were recorded in 143 asthmatic children. The overnight metyrapone
      test was performed if morning cortisol was >83 nmol/L. Spearman correlations
      coefficients (r) were calculated between 3 postmetyrapone outcomes and each
      continuous variable. A multiple linear regression model of ?postmetyrapone
      adrenocorticotropic hormone (ACTH) and a logistic regression model for HPAS were
      developed. RESULTS: Hypocortisolemia was seen in 6.1% (1.8-10.5), hypothalamic
      pituitary suppression (HPS) in 22.2% (14.5-29.9), adrenal suppression in 32.3%
      (23.7-40.9), HPAS in 16.3% (9.3-23.3), and any hypothalamic-pituitary-adrenal
      axis dysfunction in 65.1% (56.5-72.9). Log daily nasal steroid (NS) dose/m(2) was
      associated with HPAS in the logistic regression model (odds ratio = 3.7 [95%
      confidence interval: 1.1-13.6]). Daily inhaled corticosteroids (ICSs) + NS
      dose/m(2) predicted HPAS in the univariate logistic regression model (P = .038).
      Forced expiratory volume in 1 second/forced vital capacity <80% was associated
      with HPAS (odds ratio = 4.1 [95% confidence interval: 1.0-14.8]). Daily ICS +
      NS/m(2) dose was correlated with the postmetyrapone ACTH (r = -0.29, P < .001).
      BMI (P = .048) and percent adherence to ICS (P < .001) and NS (P = .002) were
      predictive of ?postmetyrapone ACTH (R(2) = .176). CONCLUSIONS: Two-thirds of
      children on corticosteroids may have hypothalamic-pituitary-adrenal axis
      dysfunction. In one-third, central function had recovered but adrenal suppression
      persisted. Predictive factors for HPAS are NS use, BMI, and adherence to ICS and
      NS.

PMID- 23147981
TI  - Pediatric providers' self-reported knowledge, practices, and attitudes about
      concussion.
AB  - OBJECTIVE: To determine the self-reported practices and attitudes surrounding
      concussion diagnosis and management in a single, large pediatric care network.
      METHODS: A cross-sectional survey was distributed to pediatric primary care and
      emergency medicine providers in a single, large pediatric care network. For all
      survey participants, practices and attitudes about concussion diagnosis and
      treatment were queried. RESULTS: There were 145 responses from 276 eligible
      providers, resulting in a 53% response rate, of which 91% (95% confidence
      interval [CI]: 86%-95%) had cared for at least 1 concussion patient in the
      previous 3 months. A Likert scale from 1 "not a barrier" to 5 "significant
      barrier" was used to assess providers' barriers to educating families about the
      diagnosis of concussion. Providers selected 4 or 5 on the scale for the following
      barriers and frequencies: inadequate training to educate 16% (95% CI: 11%-23%),
      inadequate time to educate 15% (95% CI: 12%-24%), and not my role to educate 1%
      (95% CI: 0.4%-5%). Ninety-six percent (95% CI: 91%-98%) of providers without a
      provider decision support tool (such as a clinical pathway or protocol) specific
      to concussion, and 100% (95% CI: 94%-100%) of providers without discharge
      instructions specific to concussion believed these resources would be helpful.
      CONCLUSIONS: Although pediatric primary care and emergency medicine providers
      regularly care for concussion patients, they may not have adequate training or
      infrastructure to systematically diagnose and manage these patients. Specific
      provider education, decision support tools, and patient information could help
      enhance and standardize concussion management.

PMID- 23147982
TI  - Effectiveness of protective eyewear in reducing eye injuries among high school
      field hockey players.
AB  - OBJECTIVE: To determine if injury rates differ among high school field hockey
      players in states that mandated protective eyewear (MPE) versus states with no
      protective eyewear mandate (no MPE). METHODS: We analyzed field hockey exposure
      and injury data collected over the 2009-2010 and 2010-2011 scholastic seasons
      from national and regional databases. RESULTS: Incidence of all head and face
      injuries (including eye injuries, concussion) was significantly higher in no-MPE
      states compared with MPE states, 0.69 vs 0.47 injuries per 1000 athletic
      exposures (incidence rate ratio [IRR] 1.47; 95% confidence interval [CI]: 1.04
      2.15, P = .048). Players in the no-MPE group had a 5.33-fold higher risk of eye
      injury than players in the MPE group (IRR 5.33; 95% CI: 0.71-39.25, P = .104).
      There was no significant difference in concussion rates for the 2 groups (IRR
      1.04; 95% CI: 0.63-1.75, P = .857). A larger percentage of injuries sustained by
      athletes in the no-MPE group required >10 days to return to activity (32%)
      compared with athletes in the MPE group (17%), but this difference did not reach
      statistical significance (P = .060). CONCLUSIONS: Among high school field hockey
      players, playing in a no-MPE state results in a statistically significant higher
      incidence of head and face injuries versus playing in an MPE state. Concussion
      rates among players in MPE and no-MPE states were similar, indicating that
      addition of protective eyewear did not result in more player-player contact
      injuries, challenging a perception in contact/collision sports that increased
      protective equipment yields increased injury rates.

PMID- 23147983
TI  - Pyridoxine-dependent epilepsy with elevated urinary alpha-amino adipic
      semialdehyde in molybdenum cofactor deficiency.
AB  - alpha-Amino adipic semialdehyde (alpha-AASA) accumulates in body fluids from
      patients with pyridoxine-dependent epilepsy because of mutations in antiquitin
      (ALDH7A1) and serves as the biomarker for this condition. We have recently found
      that the urinary excretion of alpha-AASA was also increased in molybdenum
      cofactor and sulfite oxidase deficiencies. The seizures in pyridoxine-dependent
      epilepsy are caused by lowered cerebral levels of pyridoxal-5-phosphate (PLP),
      the bioactive form of pyridoxine (vitamin B(6)), which can be corrected by the
      supplementation of pyridoxine. The nonenzymatic trapping of PLP by the cyclic
      form of alpha-AASA is causative for the lowered cerebral PLP levels. We describe
      2 siblings with clinically evident pyridoxine-responsive seizures associated with
      increased urinary excretion of alpha-AASA. Subsequent metabolic investigations
      revealed several metabolic abnormities, all indicative for molybdenum cofactor
      deficiency. Molecular investigations indeed revealed a known homozygous mutation
      in the MOCS2 gene. Based upon the clinically evident pyridoxine-responsive
      seizures in these 2 siblings, we recommend considering pyridoxine supplementation
      to patients affected with molybdenum cofactor or sulfite oxidase deficiencies.

PMID- 23147984
TI  - Neuromuscular stimulation of quadriceps in patients hospitalised during an
      exacerbation of COPD: a comparison of low (35 Hz) and high (50 Hz) frequencies.
AB  - BACKGROUND: Neuromuscular electrical stimulation (NMES) has shown to improve
      skeletal muscle strength and exercise capacity in stable patients with chronic
      obstructive pulmonary disease (COPD). Variations in NMES protocols are
      considerable. We aimed to compare changes in muscle strength after high-frequency
      and low-frequency NMES in patients admitted to hospital with an acute
      exacerbation of COPD. METHODS: Patients were referred for inpatient (IP)
      rehabilitation during hospitalisation for an acute worsening of their COPD. They
      received 30-minute daily NMES to both quadriceps at a frequency of 35 or 50 Hz.
      NMES intensity was titrated to patients' tolerance. Isometric quadriceps muscle
      strength and endurance walking (ESWT) time were measured at baseline and on
      hospital discharge. RESULTS: A total of 10 patients in each treatment group
      underwent NMES during hospitalisation (mean [SD] age 68.0 [+/-7.4] years, FEV1
      0.99 L [+/-0.58], FEV1/FVC 47% [+/- 27%], MRC 5 [IQR +/-1]). There were no
      significant differences in baseline characteristics between groups. Muscle
      strength (legs combined) increased in both groups regardless of the NMES
      frequency used (35 Hz--3.8 +/- 4.9; 50 Hz--3.4 +/- 5.5 kg). This was only
      significant within the 35 Hz group. The change in ESWT also showed a trend to
      increase in both groups (35 Hz--109 +/- 92.7; 50 Hz--145.6 +/- 94.7). There was
      no significant difference between groups for either outcome. CONCLUSION: NMES is
      a feasible intervention to improve muscle strength in a cohort of patients
      admitted with an exacerbation of COPD. The response appears to be independent of
      the frequency used and both were well-tolerated.

PMID- 23147985
TI  - Nebulized arformoterol: what is its place in the management of COPD?
AB  - Chronic obstructive pulmonary disease (COPD) is a serious global health burden.
      Comprehensive management of COPD includes both pharmacologic and non
      pharmacologic interventions aimed at improving disease-related functional
      capacity, health-related quality of life, and survival. The primary medications
      used for treatment of COPD are inhaled bronchodilator drugs which are delivered
      directly to the patient's airways through a number of different mechanisms.
      Arformoterol, the (R,R) enantiomer of racemic formoterol, was the first long
      acting beta agonist approved by the U.S. Food and Drug Administration (FDA) for
      nebulized delivery. We discuss the pharmacology, clinical efficacy, and safety of
      arformoterol, and provide recommendations for its use during longitudinal
      management of patients with COPD.

PMID- 23147986
TI  - Transplanting the adolescent cystic fibrosis patient: can we do it?
AB  - Bilateral lung transplantation remains a treatment for end-stage cystic fibrosis
      (CF) lung disease when there is no further medical or surgical treatment
      available. The aim of lung transplantation is to improve patient life expectancy.
      The consensus view that lung transplantation extends life in children has been
      challenged. However, challengers have faced alternative explanations of their
      finding and it is largely accepted that lung transplantation in the adolescent
      patient population is an important treatment modality. The goal of this article
      is to address these concerns and assist with developing creative approaches to
      this known challenging subset of patients. The main focus of this article will be
      to discuss the looming question: what existing evidence or best practice insights
      could improve bilateral lung transplantation outcomes for adolescent patients
      with end-stage CF?

PMID- 23147987
TI  - Effects-based marine ecological risk assessment at a polychlorinated biphenyl
      contaminated site in Saglek, Labrador, Canada.
AB  - Although the presence and distribution of polychlorinated biphenyls (PCBs) in
      Arctic marine environments has been well documented, the implications for the
      health of biota are poorly understood. In the present study, multiple lines of
      evidence, including site-specific effects data, were used to assess PCB-related
      risks to marine biota at a contaminated military site in Saglek Bay, Labrador,
      Canada, from 1997 to 1999. Risks were evaluated for three components of the
      ecosystem: benthic invertebrates, a bottom-feeding fish (shorthorn sculpin,
      Myoxocephalus scorpius), and a diving seabird (black guillemot, Cepphus grylle).
      Average sediment PCB concentrations exceeded the Canadian interim sediment
      quality guideline level by 41-fold. However, sediment toxicity testing and a
      benthic community survey showed no evidence of adverse effects. In contrast,
      shorthorn sculpin and black guillemot PCB exposures (measured as sum of 55
      congeners) were elevated enough to pose risks to survival or reproduction. Based
      on the collective evidence, the authors estimated that risks were posed by
      sediment PCB concentrations greater than 77 ng/g dry weight for black guillemots
      and 750 ng/g dry weight for shorthorn sculpins. The present study, along with two
      parallel studies, provided information to support the management decisions
      concerning potential remedial action on the contaminated sediments. This
      ecological risk assessment describes the steps and rationale taken to evaluate
      the risk posed by an area of PCB-contaminated marine sediments in an otherwise
      relatively pristine northern coastal environment.

PMID- 23147988
TI  - What do French patients and geneticists think about prenatal and preimplantation
      diagnoses in Marfan syndrome?
AB  - OBJECTIVES: Marfan syndrome (MFS) is an autosomal dominant connective tissue
      disorder with manifestations mainly involving the skeletal, ocular, and
      cardiovascular systems. The phenotypic variability observed in MFS makes genetic
      counselling difficult. Prenatal diagnosis (PND) and preimplantation genetic
      diagnosis are technically feasible when a causal mutation is identified, but both
      raise many ethical questions in this condition. Little is known about opinions
      and practices in such reproductive issues in MFS. The goal of this study was to
      report on patients' points of view and geneticists' standard practices. METHODS:
      Two different questionnaires were produced. RESULTS: Fifty geneticists filled in
      the questionnaire. Twenty-two per cent thought that PND was acceptable, 72%
      debatable and 6% not acceptable. Preimplantation genetic diagnosis was more often
      reported acceptable (34% of answers). Results varied according to the physician's
      experience with the disease. Fifty-four answers were collected for patients'
      questionnaires. Most of them (74%) were favourable to the development of prenatal
      testing, and believed that the choice should be given to parents. However, only a
      minority would opt for prenatal diagnosis for themselves. CONCLUSION: This study
      showed that the majority of patients were in favour of PND and that opinions
      among practitioners varied widely, but that overall, practitioners favoured a
      systematic multidisciplinary evaluation of the couple's request.

PMID- 23147989
TI  - Ruthenium-catalyzed reductive coupling of 1,3-enynes and aldehydes by transfer
      hydrogenation: anti-diastereoselective carbonyl propargylation.
AB  - Under the conditions of ruthenium-catalyzed transfer hydrogenation employing
      isopropanol as a source of hydrogen, isopropoxy-substituted enyne 1 b and
      aldehydes 3 a-3 l engage in reductive coupling to provide products of
      propargylation 4 a-4 l with good to complete levels of anti-diastereoselectivity.
      The unprotected tertiary hydroxy moiety of isopropoxy enyne 1 b is required to
      enforce diastereoselectivity. Deuterium-labeling studies corroborate reversible
      enyne hydrometalation in advance of carbonyl addition. As demonstrated in the
      conversion of 4 f-h and 4 k to 5 f-h and 5 k, the isopropoxy group of the product
      is readily cleaved upon exposure to aqueous sodium hydroxide to reveal the
      terminal alkyne.

PMID- 23147990
TI  - High-throughput identification of putative receptors for cancer-binding peptides
      using biopanning and microarray analysis.
AB  - Phage-display peptide biopanning has been successfully used to identify cancer
      targeting peptides in multiple models. For cancer-binding peptides,
      identification of the peptide receptor is necessary to demonstrate the mechanism
      of action and to further optimize specificity and target binding. The process of
      receptor identification can be slow and some peptides may turn out to bind
      ubiquitous proteins not suitable for further drug development. In this report, we
      describe a high-throughput method for screening a large number of peptides in
      parallel to identify peptide receptors, which we have termed "reverse
      biopanning." Peptides can then be selected for further development based on their
      receptor. To demonstrate this method, we screened a library of 39 peptides
      previously identified in our laboratory to bind specifically to cancers after
      irradiation. The reverse biopanning process identified 2 peptides, RKFLMTTRYSRV
      and KTAKKNVFFCSV, as candidate ligands for the protein tax interacting protein 1
      (TIP-1), a protein previously identified in our laboratory to be expressed in
      tumors and upregulated after exposure to ionizing radiation. We used
      computational modeling as the initial method for rapid validation of peptide-TIP
      1 binding. Pseudo-binding energies were calculated to be -360.645 kcal mol(-1), 
      487.239 kcal mol(-1), and -595.328 kcal mol(-1) for HVGGSSV, TTRYSRV, and NVFFCSV
      respectively, suggesting that the peptides would have at least similar, if not
      stronger, binding to TIP-1 compared to the known TIP-1 binding peptide HVGGSSV.
      We validated peptide binding in vitro using electrophoretic mobility shift assay,
      which showed strong binding of RKFLMTTRYSRV and the truncated form TTRYSRV. This
      method allows for the identification of many peptide receptors and subsequent
      selection of peptides for further drug development based on the peptide receptor.

PMID- 23147991
TI  - Occupational experiences and subjective well-being of mothers of children with
      ASD in Taiwan.
AB  - This study investigated the relationship between mothers' daily occupational
      experiences of productivity, restoration and pleasure with their subjective well
      being (SWB) and with their child's developmental skills. Forty caregivers
      parenting young children with autism spectrum disorders served as a convenience
      sample in this study. Participants rated their occupational experience in a time
      diary for a 1-week period and rated their SWB on the Positive and Negative Affect
      Scale and Satisfaction with Life Scale. Their child's occupational performance
      and development were evaluated using the Pediatric Daily Occupation Scale and
      Chinese Child Development Inventory. Spearman rank correlations were used to
      examine the relationship of SWB to these maternal and child factors. Mothers'
      pleasure levels were associated with two SWB measures: the positive affect and
      Satisfaction With Life Scale. Restoration levels related to positive affect only.
      Productivity levels and child factors were not significantly correlated with any
      of the SWB measures. A larger heterogeneous sample and a longitudinal study
      design to explore the fluctuation and stability of occupational experiences
      across time are recommended to examine caregivers' adaptation and/or alterations
      in SWB while adapting to their child's diagnosis and special needs.

PMID- 23147992
TI  - Surgical treatment of hepatocellular carcinoma associated with the metabolic
      syndrome.
AB  - BACKGROUND: The incidence of metabolic syndrome-associated hepatocellular
      carcinoma (MS-HCC) is increasing. However, the results following liver resection
      in this context have not been described in detail. METHODS: Data for all patients
      with metabolic syndrome as a unique risk factor for HCC who underwent liver
      resection between 2000 and 2011 were retrieved retrospectively from an
      institutional database. Pathological analysis of the underlying parenchyma
      included fibrosis and non-alcoholic fatty liver disease activity score. Patients
      were classified as having normal or abnormal underlying parenchyma. Their
      characteristics and outcomes were compared. RESULTS: A total of 560 resections
      for HCC were performed in the study interval. Sixty-two patients with metabolic
      syndrome, of median age 70 (range 50-84) years, underwent curative hepatectomy
      for HCC, including 32 major resections (52 per cent). Normal underlying
      parenchyma was present in 24 patients (39 per cent). The proportion of resected
      HCCs labelled as MS-HCC accounted for more than 15 per cent of the entire HCC
      population in more recent years. Mortality and major morbidity rates were 11 and
      58 per cent respectively. Compared with patients with normal underlying liver,
      patients with abnormal liver had increased rates of mortality (0 versus 18 per
      cent; P = 0.026) and major complications (13 versus 42 per cent; P = 0.010). In
      multivariable analysis, a non-severely fibrotic yet abnormal underlying
      parenchyma was a risk factor for major complications (hazard ratio 5.66, 95 per
      cent confidence interval 1.21 to 26.52; P = 0.028). The 3-year overall and
      disease-free survival rates were 75 and 70 per cent respectively, and were not
      influenced by the underlying parenchyma. CONCLUSION: HCC in patients with
      metabolic syndrome is becoming more common. Liver resection is appropriate but
      carries a high risk, even in the absence of severe fibrosis. Favourable long-term
      outcomes justify refinements in the perioperative management of these patients.

PMID- 23147993
TI  - A novel HLA-A*0201 restricted peptide derived from cathepsin G is an effective
      immunotherapeutic target in acute myeloid leukemia.
AB  - PURPOSE: Immunotherapy targeting aberrantly expressed leukemia-associated
      antigens has shown promise in the management of acute myeloid leukemia (AML).
      However, because of the heterogeneity and clonal evolution that is a feature of
      myeloid leukemia, targeting single peptide epitopes has had limited success,
      highlighting the need for novel antigen discovery. In this study, we characterize
      the role of the myeloid azurophil granule protease cathepsin G (CG) as a novel
      target for AML immunotherapy. EXPERIMENTAL DESIGN: We used Immune Epitope
      Database and in vitro binding assays to identify immunogenic epitopes derived
      from CG. Flow cytometry, immunoblotting, and confocal microscopy were used to
      characterize the expression and processing of CG in AML patient samples, leukemia
      stem cells, and normal neutrophils. Cytotoxicity assays determined the
      susceptibility of AML to CG-specific cytotoxic T lymphocytes (CTL). Dextramer
      staining and cytokine flow cytometry were conducted to characterize the immune
      response to CG in patients. RESULTS: CG was highly expressed and ubiquitinated in
      AML blasts, and was localized outside granules in compartments that facilitate
      antigen presentation. We identified five HLA-A*0201 binding nonameric peptides
      (CG1-CG5) derived from CG, and showed immunogenicity of the highest HLA-A*0201
      binding peptide, CG1. We showed killing of primary AML by CG1-CTL, but not normal
      bone marrow. Blocking HLA-A*0201 abrogated CG1-CTL-mediated cytotoxicity, further
      confirming HLA-A*0201-dependent killing. Finally, we showed functional CG1-CTLs
      in peripheral blood from AML patients following allogeneic stem cell
      transplantation. CONCLUSION: CG is aberrantly expressed and processed in AML and
      is a novel immunotherapeutic target that warrants further development.

PMID- 23147994
TI  - Endoglin (CD105) contributes to platinum resistance and is a target for tumor
      specific therapy in epithelial ovarian cancer.
AB  - PURPOSE: Endoglin (CD105) is a membranous protein overexpressed in tumor
      associated endothelial cells, chemoresistant populations of ovarian cancer cells,
      and potentially stem cells. Our objective was to evaluate the effects and
      mechanisms of targeting endoglin in ovarian cancer. EXPERIMENTAL DESIGN: Global
      and membranous endoglin expression was evaluated in multiple ovarian cancer
      lines. In vitro, the effects of siRNA-mediated endoglin knockdown with and
      without chemotherapy were evaluated by MTT assay, cell-cycle analysis, alkaline
      comet assay, gamma-H2AX foci formation, and quantitative PCR. In an orthotopic
      mouse model, endoglin was targeted with chitosan-encapsulated siRNA with and
      without carboplatin. RESULTS: Endoglin expression was surprisingly predominantly
      cytoplasmic, with a small population of surface-positive cells. Endoglin
      inhibition decreased cell viability, increased apoptosis, induced double-stranded
      DNA damage, and increased cisplatin sensitivity. Targeting endoglin downregulates
      expression of numerous DNA repair genes, including BARD1, H2AFX, NBN, NTHL1, and
      SIRT1. BARD1 was also associated with platinum resistance, and was induced by
      platinum exposure. In vivo, antiendoglin treatment decreased tumor weight in both
      ES2 and HeyA8MDR models when compared with control (35%-41% reduction, P < 0.05).
      Endoglin inhibition with carboplatin was associated with even greater inhibitory
      effect when compared with control (58%-62% reduction, P < 0.001). CONCLUSIONS:
      Endoglin downregulation promotes apoptosis, induces significant DNA damage
      through modulation of numerous DNA repair genes, and improves platinum
      sensitivity both in vivo and in vitro. Antiendoglin therapy would allow dual
      treatment of both tumor angiogenesis and a subset of aggressive tumor cells
      expressing endoglin and is being actively pursued as therapy in ovarian cancer.

PMID- 23147996
TI  - The severity of neural invasion is associated with shortened survival in colon
      cancer.
AB  - PURPOSE: Neural invasion (NI) is a histopathologic feature of colon cancer that
      receives little consideration. Therefore, we conducted a morphologic and
      functional characterization of NI in colon cancer. EXPERIMENTAL DESIGN: NI was
      investigated in 673 patients with colon cancer. Localization and severity of NI
      was determined and related to patient's prognosis and survival. The neuro
      affinity of colon cancer cells (HT29, HCT-116, SW620, and DLD-1) was compared
      with pancreatic cancer (T3M4 and SU86.86) and rectal cancer cells (CMT-93) in the
      in vitro three-dimensional (3D)-neural-migration assay and analyzed via live-cell
      imaging. Immunoreactivity of the neuroplasticity marker GAP-43, and the
      neurotrophic-chemoattractant factors Artemin and nerve growth factor (NGF), was
      quantified in colon cancer and pancreatic cancer nerves. Dorsal root ganglia of
      newborn rats were exposed to supernatants of colon cancer, rectal cancer, and
      pancreatic cancer cells and neurite density was determined. RESULTS: NI was
      detected in 210 of 673 patients (31.2%). Although increasing NI severity scores
      were associated with a significantly poorer survival, presence of NI was not an
      independent prognostic factor in colon cancer. In the 3D migration assay, colon
      cancer and rectal cancer cells showed much less neurite-targeted migration when
      compared with pancreatic cancer cells. Supernatants of pancreatic cancer and
      rectal cancer cells induced a much higher neurite density than those of colon
      cancer cells. Accordingly, NGF, Artemin, and GAP-43 were much more pronounced in
      nerves in pancreatic cancer than in colon cancer. CONCLUSION: NI is not an
      independent prognostic factor in colon cancer. The lack of a considerable
      biologic affinity between colon cancer cells and neurons, the low expression
      profile of colonic nerves for chemoattractant molecules, and the absence of a
      major neuroplasticity in colon cancer may explain the low prevalence and impact
      of NI in colon cancer.

PMID- 23147997
TI  - Vaccination with irradiated tumor cells pulsed with an adjuvant that stimulates
      NKT cells is an effective treatment for glioma.
AB  - PURPOSE: The prognosis for patients with glioblastoma multiforme (GBM) remains
      extremely poor despite recent treatment advances. There is an urgent need to
      develop novel therapies for this disease. EXPERIMENTAL DESIGN: We used the
      implantable GL261 murine glioma model to investigate the therapeutic potential of
      a vaccine consisting of intravenous injection of irradiated whole tumor cells
      pulsed with the immuno-adjuvant alpha-galactosylceramide (alpha-GalCer). RESULTS:
      Vaccine treatment alone was highly effective in a prophylactic setting. In a more
      stringent therapeutic setting, administration of one dose of vaccine combined
      with depletion of regulatory T cells (Treg) resulted in 43% long-term survival
      and the disappearance of mass lesions detected by MRI. Mechanistically, the alpha
      GalCer component was shown to act by stimulating "invariant" natural killer-like
      T cells (iNKT cells) in a CD1d-restricted manner, which in turn supported the
      development of a CD4(+) T-cell-mediated adaptive immune response. Pulsing alpha
      GalCer onto tumor cells avoided the profound iNKT cell anergy induced by free
      alpha-GalCer. To investigate the potential for clinical application of this
      vaccine, the number and function of iNKT cells was assessed in patients with GBM
      and shown to be similar to age-matched healthy volunteers. Furthermore,
      irradiated GBM tumor cells pulsed with alpha-GalCer were able to stimulate iNKT
      cells and augment a T-cell response in vitro. CONCLUSIONS: Injection of
      irradiated tumor cells loaded with alpha-GalCer is a simple procedure that could
      provide effective immunotherapy for patients with high-grade glioma.

PMID- 23147998
TI  - Surveying the territory.

PMID- 23147995
TI  - miRNA-34b inhibits prostate cancer through demethylation, active chromatin
      modifications, and AKT pathways.
AB  - PURPOSE: miRNAs can act as oncomirs or tumor-suppressor miRs in cancer. This
      study was undertaken to investigate the status and role of miR-34b in prostate
      cancer. EXPERIMENTAL DESIGN: Profiling of miR-34b was carried out in human
      prostate cancer cell lines and clinical samples by quantitative real-time PCR and
      in situ hybridization. Statistical analyses were done to assess
      diagnostic/prognostic potential. Biological significance was elucidated by
      carrying out a series of experiments in vitro and in vivo. RESULTS: We report
      that miR-34b is silenced in human prostate cancer and the mechanism is through
      CpG hypermethylation. miR-34b directly targeted methyltransferases and
      deacetylases resulting in a positive feedback loop inducing partial demethylation
      and active chromatin modifications. miR-34b expression could predict overall and
      recurrence-free survival such that patients with high miR-34b levels had longer
      survival. Functionally, miR-34b inhibited cell proliferation, colony formation,
      migration/invasion, and triggered G(0)/G(1) cell-cycle arrest and apoptosis by
      directly targeting the Akt and its downstream proliferative genes. miR-34b caused
      a decline in the mesenchymal markers vimentin, ZO1, N-cadherin, and Snail with an
      increase in E-cadherin expression, thus inhibiting epithelial-to-mesenchymal
      transition. Finally we showed the antitumor effect of miR-34b in vivo. MiR-34b
      caused a dramatic decrease in tumor growth in nude mice compared with cont-miR.
      CONCLUSION: These findings offer new insight into the role of miR-34b in the
      inhibition of prostate cancer through demethylation, active chromatin
      modification, and Akt pathways and may provide a rationale for the development of
      new strategies targeting epigenetic regulation of miRNAs for the treatment of
      prostate cancer.

PMID- 23147999
TI  - CAFM Educational Research Alliance (CERA) 2011 Residency Director survey:
      background, methods, and respondent characteristics.
AB  - BACKGROUND AND OBJECTIVES: Due to the scarcity of funds for educational research
      it is difficult for many clinician educators to conduct meaningful educational
      research. The Council of Academic Family Medicine Educational Research Alliance
      (CERA) was created to provide an infrastructure to facilitate educational
      research in family medicine. CERA's first major initiative was an omnibus survey
      of family medicine residency directors. This survey incorporated several distinct
      subprojects focusing on different topic areas. Members of the Association of
      Family Medicine Residency Directors (AFMRD) were surveyed electronically in 2011
      using the infrastructure of the Society of Teachers of Family Medicine. The
      response rate for the survey was 38% (172/452). The majority of the programs were
      community based, university affiliated, and well established, with a mean of 31.2
      years of providing residency training. Program directors were predominantly male
      (72%) and had a mean duration of 6.8 years in that role. This 2011 Family
      Medicine Residency Director survey is the first step in building the CERA
      infrastructure. Several more CERA surveys of other distinct populations have
      already been put into the field. CERA represents an important conduit for
      academic family physicians to produce high-quality educational research. The
      creation of CERA is a key step toward making educational research in family
      medicine more achievable, more rigorous, and more generalizable.

PMID- 23148000
TI  - Physical fitness during medical school: a 4-year study at the Uniformed Services
      University.
AB  - BACKGROUND AND OBJECTIVES: Medical school is stressful. Students commonly exhibit
      changes in dietary and physical activity patterns in response. We tracked
      measurements of physical fitness over 4 years in a cohort of students at the
      Uniformed Services University. METHODS: Validated measures for specific
      components of physical fitness were measured in 170 students (94% of the Class of
      2011) over the course of 4 years. Measurements included: (1) height and weight
      (body composition), (2) timed push-ups and sit-ups (muscular endurance), and (3)
      timed run (aerobic endurance). These measurements are part of annual physical
      readiness testing required for active duty service in the US military. RESULTS:
      Muscular endurance and aerobic capacity declined significantly over the 4 years
      of medical school. Changes in physical fitness were most pronounced during the
      preclinical years. There were inconsistent changes in body composition among
      students in the Army, Navy, and Air Force. Composite fitness scores declined
      significantly in Army and Navy students but not in the Air Force. CONCLUSIONS:
      Individual levels of physical fitness decline during medical school. Declines are
      most notable during the preclinical years. To promote student wellness, medical
      schools should incorporate student wellness activities as a routine part of the
      curriculum.

PMID- 23148001
TI  - Can we effectively use the two-item PHQ-2 to screen for postpartum depression?
AB  - BACKGROUND AND OBJECTIVES: Postpartum depression screening is widely advocated to
      identify and treat affected individuals given the significant impact of this
      disorder on patients and their families. An effective, efficient method is needed
      to improve compliance with screening, which has led to an increased interest in
      the use of the two-item Patient Health Questionnaire 2 (PHQ-2). The aim of this
      study was to determine the sensitivity and specificity of the PHQ-2 in screening
      for postpartum depression. METHODS: A prospective convenience study was conducted
      among 200 postpartum women attending their postpartum or 4- and 6-month well
      child visits at a multiethnic family medicine residency center. The sensitivity
      and specificity of the PHQ-2 was determined by using the well validated Edinburgh
      Postnatal Depression Scale (EPDS) as the gold standard. Positive responses to
      either scale led to further evaluation and referral. RESULTS: The sensitivity of
      the PHQ-2 was 100%, and the specificity was 79.3% using the EPDS as the reference
      standard. In addition, the PHQ-2 identified an additional four/nine women who
      were subsequently diagnosed with postpartum depression based on follow up of
      their positive screens. CONCLUSIONS: This study supports previous findings
      indicating that the PHQ-2 can be an effective tool in screening for postpartum
      depression.

PMID- 23148002
TI  - Mental health treatment by family physicians: current practices and preferences.
AB  - BACKGROUND AND OBJECTIVES: Family physicians are trained to assess mental health
      symptoms and provide some mental health interventions to their patients. Because
      of obstacles to referring patients to mental health specialists, many family
      physicians independently provide outpatient mental health treatment such as brief
      office counseling. Questions exist regarding physicians' interest in, perceived
      competence with, and their actual practice of brief office counseling in family
      medicine. METHODS: Surveys were administered to physicians at 11 family medicine
      residency programs in Florida. RESULTS: Physicians regularly evaluate, diagnose,
      and treat patients with mild to moderate mental health disorders. Physicians
      prefer to evaluate patients themselves but refer patients who require counseling
      to specialists. However, physicians often provide brief office counseling
      themselves. Physicians believe they have the knowledge and skills to competently
      and effectively provide brief office counseling to their patients. They also
      believe that patients are receptive to and prefer to receive brief office
      counseling from their family physician rather than from a mental health
      specialist. CONCLUSIONS: Physicians are willing and feel competent to identify
      and treat patients with mental disorders in the family medicine outpatient
      setting, including the provision of brief office counseling. Further research is
      needed to understand what effective mental health interventions can efficiently
      be taught to family physicians. Having family physicians treat mental health
      disorders may lead to greater patient satisfaction, improved chronic care
      management, and a positive impact on quality of care.

PMID- 23148003
TI  - Graduate medical education and primary care workforce: a CERA study.
AB  - BACKGROUND: In the next 10 to 15 years, the Association of American Medical
      Colleges (AAMC) estimates a shortage of physicians. In conjunction, the demand
      for primary care physicians will increase, the type of physician associated with
      better population health at lower health care costs. The objective of this study
      is to examine the opinions of family medicine residency directors (FMRD)
      regarding the potential impact of recent publicized recommendations on the
      primary care physician workforce in the United States. METHODS: This project is
      part of a larger CERA omnibus survey with survey methods and sample demographics
      presented previously. Additional analysis was conducted using chi square and
      logistic regression using type of residency, size of community, years as program
      director, year program began, gender, and geographic region as predictors of
      agreement. RESULTS: A large proportion of responding FMRD disagree or strongly
      disagree that increasing medical school size or number of total resident
      positions in all specialties would result in an increase in the number of medical
      school graduates choosing a career in primary care Most respondents feel that
      increasing compensation for those practicing in primary care would have greatest
      impact on increasing medical school graduates who choose primary care. A minority
      of responding directors feel the length of family medicine residency training
      should be 4 years. DISCUSSION: While numerous recommendations have recently been
      made, most responding FMRD feel that changing reimbursement for primary care
      physicians would have the greatest impact on the workforce.

PMID- 23148004
TI  - Shots by STFM: value of immunization software to family medicine residency
      directors: a CERA study.
AB  - BACKGROUND AND OBJECTIVES: The Group on Immunization Education (GIE) of the
      Society of Teachers of Family Medicine (STFM) has developed Shots by STFM
      immunization software, which is available free of charge for a variety of
      platforms. It is routinely updated with the Center for Disease Control and
      Prevention's (CDC's) most recent immunization schedules. Successful development
      and marketing of teaching resources requires periodic evaluation of their use and
      value to their target audience. This study was undertaken to evaluate the 2011
      version of Shots by STFM. METHODS: Family medicine residency directors were
      surveyed about their use of Shots by STFM for teaching residents and their
      ratings of its features. RESULTS: The response rate for the survey was 38%
      (172/452). While awareness of Shots by STFM among responding residency directors
      was low (57%), ratings by those using the resource were excellent. Thirty percent
      of respondents recommend or require their residents to use Shots by STFM.
      CONCLUSIONS: Better marketing of Shots by STFM to family medicine residency
      directors seems to be indicated.

PMID- 23148005
TI  - Assessing oral health curriculum in US family medicine residency programs: a CERA
      study.
AB  - BACKGROUND AND OBJECTIVES: During the past decade, national initiatives have
      called for improved oral health training for physicians. We do not know, however,
      how family medicine residency programs have answered this call. METHODS: Family
      medicine residency directors completed a survey that asked how many hours of oral
      health teaching are included in their programs in addition to what topics are
      covered and the perceived barriers to this education. The response rate was 35%.
      RESULTS: A total of 72% of respondents agreed that oral health is an important
      topic, but only 32% are satisfied with their residents' competency in oral
      health. Barriers to this education included competing priorities (85%),
      inadequate time (69%), and lack of faculty expertise (52%). CONCLUSIONS: The
      findings suggest that programs are including more hours than in previous years,
      yet continued efforts are needed to cover core oral health topics and increase
      the competency of family medicine residents. Awareness of STFM's Smiles for Life
      and use of its modules were associated with increased hours of training.

PMID- 23148006
TI  - An ounce of prevention: how are we managing the early assessment of residents'
      clinical skills?: A CERA study.
AB  - BACKGROUND AND OBJECTIVES: Clinical skills deficits in residents are common but
      when identified early can result in decreased cost, faculty time, and stress
      related to remediation. There is currently no accepted best practice for early
      assessment of incoming residents' clinical skills. This study describes the
      current state of early PGY-1 clinical skills assessment in US family medicine
      residencies. METHODS: Eleven questions were embedded in the nationwide CERA
      survey to US family medicine residency directors regarding the processes,
      components, and barriers to early PGY-1 assessment. Responses are described, and
      bivariate analyses of the relationship between assessment variables and
      percentage of international medical graduates (IMGs), type of program, and
      barriers to implementation were performed using chi square testing. RESULTS:
      Almost four of five (78.4%) responding programs conduct formal early assessments
      to establish baseline clinical skills (89.6%), provide PGY-1 residents with a
      guide to focus their learning goals (71.6%), and less often, in response to
      resident performance problems (34.3%). Barriers to implementing PGY-1 early
      assessment programs include cost of faculty time (56.3%), cost of tools (42.1%),
      and time for the assessment during the PGY-1 resident's schedule (41.0%). Cost of
      faculty time and time for assessment from the PGY-1 resident's schedule were
      statistically significant major/insurmountable barriers for community-based, non
      university-affiliated programs. CONCLUSIONS: Early PGY-1 assessments with locally
      developed tools for direct observation are commonly used in family medicine
      residency programs. Assessment program development should be targeted toward
      using existing, validated tools during the PGY-1 resident's patient care
      schedule.

PMID- 23148007
TI  - Exploratory analysis of patients' motivations to quit smoking and participate in
      smoking cessation classes.
AB  - BACKGROUND AND OBJECTIVES: Significant research has evaluated the impacts of
      smoking, the impacts of exposure to secondhand smoke, the effectiveness of a
      variety of social and individual interventions for smoking cessation, and the
      frequency at which physicians discuss smoking cessation with their patients. 
      Little research has addressed barriers to physician-initiated discussion and
      intervention related to smoking cessation, especially pertaining to resident
      physicians treating low-income patients. The existing research indicates that
      physicians have low expectations regarding patients' desires to quit smoking and
      often wait to discuss smoking cessation with patients until the patient broaches
      the subject. The purpose of this pilot was to identify trends in smoking, desire
      for smoking cessation, and desire to participate in smoking cessation classes at
      the family practice clinic. METHODS: Patients completed a survey eliciting
      demographic information, smoking behavior, presence of chronic illness, desire to
      quit smoking, and reasons for wanting to quit smoking. RESULTS: Higher rates of
      smoking and lower rates of desired cessation were identified. However, among
      patients contemplating smoking cessation, a relatively high number desired
      cessation classes. Higher numbers of failed quit attempts were predictive of
      increases odds of both wanting to quit and desire for cessation classes. Other
      predictors of cessation desire and class participation are discussed.
      CONCLUSIONS: Based on the current research, physicians are encouraged to follow
      practice guidelines, asking all patients about smoking behavior and assisting in
      their efforts to quit, especially those who have previously been unsuccessful in
      the past.

PMID- 23148008
TI  - RAFT (Resident Assessment Facilitation Team): supporting resident well-being
      through an integrated advising and assessment process.
AB  - BACKGROUND AND OBJECTIVES: During medical residency, indicators of well-being
      decline while rates of burnout increase. As part of a Preparing the Personal
      Physician for Practice (P4) innovation, this residency program used a
      relationship-centered periodic resident assessment process to reinforce values of
      adult learning within the curriculum. It was predicted that the revised
      assessment process would contribute to an improved educational climate for
      residents as reflected in global scores of well-being either remaining at the
      same level or improving throughout residency. METHODS: Resident Assessment
      Facilitation Team (RAFT) is an innovative feedback process utilizing small-group
      dialogue that replaces the traditional semi-annual, faculty-wide review of
      resident performance. As a pilot study to investigate the impact of RAFT, the
      Arizona Integrative Outcome Scale (AIOS) was used to describe trends in the well
      being of P4 resident cohorts from internship through PGY-3. A comparison group
      was derived from a resident cohort that started before full implementation of the
      P4 curriculum and also completed the AIOS. RESULTS: ANOVA comparing AIOS scores
      across PGY cohort groups was not significant. An independent samples t test
      comparing AIOS scores from the PGY-3 pre-P4 group with those of the PGY-3 post-P4
      group was also not significant. Although this pilot study was not powered for a
      complete inferential analysis, the descriptive data suggest a downward trend in
      the pre-RAFT group and stable measures of well-being in the post-RAFT group.
      CONCLUSIONS: The trend in our pilot data suggests a stability of well-being among
      our residents that contrasts with patterns of resident burnout noted in existing
      research. The RAFT has become a key feature of our assessment and advising
      culture that is intended to mitigate the deleterious effects of more autocratic
      assessment processes. It may also be an important factor in the stability of
      resident well-being indicated by this pilot.

PMID- 23148009
TI  - Mrs Steadman's lesson.

PMID- 23148010
TI  - Working part time in academic family medicine.

PMID- 23148011
TI  - Health care economics, the PCMH, and education for the future: the importance of
      prospective care coordination payments.

PMID- 23148013
TI  - Accessing the coordination chemistry of phosphorus(I) zwitterions.
AB  - Go for the gold! Incorporating a borate anion into the backbone of a
      triphosphenium cation produces a unique zwitterionic phosphanide that can
      coordinate to one or two {AuCl} fragments depending on the steric bulk of the
      ligand (see picture; Au yellow, P purple, Cl green). Computational investigations
      show that in this MU-type ligand, the phosphorus atom behaves only as a sigma,pi
      donor.

PMID- 23148014
TI  - Quantification of leachate discharged to groundwater using the water balance
      method and the hydrologic evaluation of landfill performance (HELP) model.
AB  - Landfills are a source of groundwater pollution in Gaza Strip. This study focused
      on Deir Al Balah landfill, which is a unique sanitary landfill site in Gaza Strip
      (i.e., it has a lining system and a leachate recirculation system). The objective
      of this article is to assess the generated leachate quantity and percolation to
      the groundwater aquifer at a specific site, using the approaches of (i) the
      hydrologic evaluation of landfill performance model (HELP) and (ii) the water
      balance method (WBM). The results show that when using the HELP model, the
      average volume of leachate discharged from Deir Al Balah landfill during the
      period 1997 to 2007 was around, 6800 m3/year. Meanwhile, the average volume of
      leachate percolated through the clay layer was 550 m3/year, which represents
      around 8% of the generated leachate. Meanwhile, the WBM indicated that the
      average volume of leachate discharged from Deir Al Balah landfill during the same
      period was around 7660 m3/year--about half of which comes from the moisture
      content of the waste, while the remainder comes from the infiltration of
      precipitation and re-circulated leachate. Therefore, the estimated quantity of
      leachate to groundwater by these two methods was very close. However, compared
      with the measured leachate quantity, these results were overestimated and
      indicated a dangerous threat to the groundwater aquifer, as there was no
      separation between municipal, hazardous and industrial wastes, in the area.

PMID- 23148015
TI  - Reference ranges of atrioventricular valve areas by means of four-dimensional
      ultrasonography using spatiotemporal image correlation in the rendering mode.
AB  - OBJECTIVE: This study aims to determine reference curves for fetal
      atrioventricular valve areas by means of three-dimensional ultrasound using the
      spatiotemporal image correlation (STIC) software. METHODS: This was a cross
      sectional prospective study on 328 normal fetuses between the 18th and the 33rd
      weeks of pregnancy. In order to obtain valve areas, the four heart chambers plane
      was used with the fetus in a dorsal posterior position. To construct reference
      ranges, a linear regression model was used, adjusted according to the coefficient
      of determination (R(2)). To calculate the reproducibility of the tricuspid valve
      area, the intraclass coefficient correlation (ICC) was used. RESULTS: The mean
      areas of the tricuspid and mitral valves ranged from 0.19 +/- 0.08 and 0.20 +/-
      0.10 cm(2) in the 18th week to 0.93 +/- 0.31 and 1.06 +/- 0.39 cm(2) in the 33rd
      week, respectively. The intra-observer and interobserver reproducibility was
      excellent with ICC = 0.997 and 0.933, respectively. CONCLUSIONS: Reference curves
      for fetal atrioventricular valve areas were determined and presented good
      reproducibility.

PMID- 23148016
TI  - A dimensional approach to measuring anxiety for DSM-5.
AB  - In preparation for DSM-5's planned inclusion of dimensional assessments of
      psychopathology as a complement to traditional categorical diagnoses, we
      developed brief self-rated scales for anxiety disorders that are consistent in
      content and structure. In the present paper, we discuss the creation of the
      scales and examine their psychometric properties and clinical sensitivity. Phase
      One assessed psychometric properties of the initial versions of the scales in a
      large non-clinical sample (n = 702). Phase Two assessed the psychometric
      properties of revised versions of the scales, including test-retest reliability,
      in a non-clinical sample (n = 57). Phase Three examined the scales' psychometric
      properties and relationship with clinician ratings of disorder severity in a
      clinical sample (n = 48). The scales demonstrated internal consistency (alpha =
      0.85-0.92), convergent validity (r(s)  = 0.39-0.69), and test-retest reliability
      in the non-clinical samples (ICC = 0.51-0.81). In the clinical sample, the scales
      demonstrated significantly higher total scores than in the non-clinical sample
      (Cohen's d = 0.72-1.50) and moderate to high correlations with clinician ratings
      of disorder severity (r = 0.43-0.82) Although further evaluation and refinement
      of the scales (particularly the specific phobia and agoraphobia scales) is
      needed, the results provide preliminary support for the use of these scales in
      DSM-5 and thus take an important step toward the integration of standardized
      dimensional measurement into the diagnosis of anxiety disorders.

PMID- 23148017
TI  - Rhizome of Anemarrhena asphodeloides counteracts diabetic ophthalmopathy
      progression in streptozotocin-induced diabetic rats.
AB  - Diabetic ophthalmopathy (DO) impairs patients' eyesight and even causes
      blindness. Here, we investigated the effect of 60% ethanol extract of the rhizome
      of Anemarrhenae asphodeloides (ERA), which is commonly used in Chinese medicine
      formulae in treating diabetes, on DO progression. Blood glucose, insulin,
      advanced glycation end products (AGE), super oxygen dehydrogenises (SOD),
      malondialdehyde (MDA) and glutathione peroxidase (GSH-Px) levels in serum and
      sorbitol concentration in the lens were measured. Retinal endothelium/pericyte
      (E/P) ratio was evaluated, and structural changes of the retina and lens were
      observed. Effects of mangiferin and neomangiferin, the two major components of
      ERA, on subnormal growth of pericytes induced by high glucose were also detected.
      It was found that the activities of SOD and GSH-Px in serum were increased,
      whereas MDA and AGE levels in serum and sorbitol concentration in the lens were
      decreased in ERA-treated DO rats. E/P ratio was decreased, and the pathological
      changes of the lens and retina were alleviated by ERA treatment. Moreover, the
      subnormal growth of pericytes induced by high glucose was ameliorated by
      mangiferin and neomangiferin. These results indicated that ERA could effectively
      prevent DO progression in streptozotocin-induced diabetic rats, and mangiferin
      and neomangiferin may be the main effective components.

PMID- 23148018
TI  - Minimal-access colorectal surgery is associated with fewer adhesion-related
      admissions than open surgery.
AB  - BACKGROUND: This study aimed to describe national intermediate-term admission
      rates for incisional hernia or clinically apparent adhesions following colorectal
      surgery, and to compare rates following laparoscopic and open approaches.
      METHODS: Patients undergoing primary colorectal resection between 2002 and 2008
      were included from the Hospital Episode Statistics database. Subsequent inpatient
      admissions were extracted for up to 3 years after the initial operation or to the
      end of the study period. Outcomes examined were admissions with a diagnosis of,
      or operative interventions for, incisional hernia or adhesions. RESULTS: A total
      of 187 148 patients were included between 2002 and 2008, with median follow-up of
      31.8 (interquartile range 13.1-35.3) months. Some 8885 (4.7 per cent) of these
      patients were admitted with a diagnosis of, or underwent a repair of, an
      incisional hernia. In multiple regression analysis, use of laparoscopy was not a
      predictor of operative intervention for incisional hernia (odds ratio 1.09, 95
      per cent confidence interval (c.i.) 0.99 to 1.21; P = 0.083). Some 15 125 (8.1
      per cent) of the patients were admitted with a diagnosis of adhesions or had a
      procedure for division of adhesions. Overall, 3.5 per cent (6637 of 187 148) of
      patients underwent adhesiolysis. Patients selected for a laparoscopic procedure
      had lower rates of admission for adhesions (6.3 per cent (692 of 11 013) for
      laparoscopic versus 8.2 per cent (14 433 of 176 135) for open surgery; P < 0.001)
      and reintervention for adhesions (2.8 per cent (305 of 11 013) versus 3.6 per
      cent (6325 of 176 135) respectively; P < 0.001) than those undergoing an open
      procedure. In multiple regression analysis, patients selected for a laparoscopic
      procedure had lower subsequent intervention rates for adhesions (odds ratio 0.80,
      95 per cent c.i. 0.71 to 0.90; P < 0.001). DISCUSSION: Patients undergoing
      colorectal resection who are selected for the laparoscopic approach have a lower
      risk of developing clinically significant adhesions.

PMID- 23148019
TI  - Discovery of a novel aggregation domain in the huntingtin protein: implications
      for the mechanisms of Htt aggregation and toxicity.
AB  - Aggravating aggregation: an N-terminal domain that is in close proximity to the
      polyQ domain in the huntingtin protein, htt105-138, is shown to be highly
      aggregation prone. Potential cross-talk between this domain and the polyQ region
      may play a central role in regulating the aggregation and toxicity of Htt-N
      terminal fragments.

PMID- 23148020
TI  - Exoglucanase-encoding genes from three Wickerhamomyces anomalus killer strains
      isolated from olive brine.
AB  - Wickerhamomyces anomalus killer strains are important for fighting pathogenic
      yeasts and for controlling harmful yeasts and bacteria in the food industry.
      Targeted disruption of key genes in beta-glucan synthesis of a sensitive
      Saccharomyces cerevisiae strain conferred resistance to the toxins of W. anomalus
      strains BS91, BCA15 and BCU24 isolated from olive brine. Competitive inhibition
      of the killing activities by laminarin and pustulan refer to beta-1,3- and beta
      1,6-glucans as the main primary toxin targets. The extracellular exoglucanase
      encoding genes WaEXG1 and WaEXG2 from the three strains were sequenced and were
      found to display noticeable similarities to those from known potent W. anomalus
      killer strains.

PMID- 23148021
TI  - Expression levels of neuroimmune biomarkers in hypothalamus of allergic mice
      after phthalate exposure.
AB  - Previously, we demonstrated that maternal exposure to phthalates enhances atopic
      dermatitis in male mouse offspring. However, whether phthalate exposure affects
      neuroimmune biomarkers in allergic mice has not yet been studied. Di-(2
      ethylhexyl) phthalate (DEHP) and di-isononyl phthalate (DINP) are environmental
      chemicals that are commonly used as plasticizers. This study was designed to
      investigate the expression levels of neuroimmune biomarkers in the hypothalamus
      of a murine model of allergic asthma after phthalate exposure throughout
      juvenility until adulthood. Six-week-old C3H/HeJ Jcl male mice were treated with
      DEHP or DINP (0, 0.02, 0.4 or 8 nmol per body per week) and ovalbumin (OVA; 1 ug
      per body per 2 weeks) for 7 weeks intratracheally. On the day after the
      completion of the phthalate and OVA treatment, the hypothalamus from each mouse
      was collected, and the mRNA expression levels of neuroimmune biomarkers were
      examined using a real-time RT-PCR analysis. The mRNA expression levels of the
      proinflammatory cytokines interleukin (IL)-1beta and tumor necrosis factor (TNF)
      alpha, the chemokine CCL3, the transcription factor nuclear factor (NF)-kappaB,
      the oxidative stress marker heme-oxygenase (HO)1, a nerve growth factor, and the
      microglia marker Iba1 were remarkably up-regulated in the hypothalami of mice
      treated with 8 nmol of DEHP in the presence of the allergen. However, no
      significant changes were observed, except for reductions in the TNF-alpha and
      CCL2 mRNA levels, in mice exposed to DINP combined with the allergen. This study
      is the first report to show that high-dose DEHP exposure throughout juvenility
      until adulthood may induce neuroinflammation by modulating neuroimmune biomarkers
      in the hypothalami of allergic mice.

PMID- 23148022
TI  - The effects of monetary and social rewards on task performance in children and
      adolescents: liking is not enough.
AB  - The current study compared the effects of reward anticipation on task performance
      in children and adolescents (8-16 years old) using monetary and various social
      rewards. Eighty-five typically developing children undertook the Monetary
      Incentive Delay (MID) task. Of these 44 also undertook the Social Incentive Delay
      (SID-basic) task where social reward was operationalized as a smiling face and
      spoken compliments. Forty-one children participated in the SID-plus where points
      were added to a pictogram with written compliments. In a preparatory validation
      study participants were asked howmuch they liked the SID-basic rewards.Results
      showed that there was an effect of reward size on accuracy and RT in both the MID
      task and SID-plus, but not SID-basic. Subjective value of the SID-basic rewards
      was rated higher with hypothesized increasing reward intensity. In conclusion,
      although the social rewards in SID-basic were liked by children andadolescents in
      the validation study, they had no effect on the behaviour. Only when points were
      added (SID-plus), anticipated social reward affected task performance. Thus our
      results highlight (i) the difference between likeability andreinforcing quality
      and (ii) the need for a quantifiable element to rewards for themto be reinforcing
      for children.

PMID- 23148023
TI  - Pharmacokinetics of hesperetin and naringenin in the Zhi Zhu Wan, a traditional
      Chinese medicinal formulae, and its pharmacodynamics study.
AB  - Zhi Zhu Wan (ZZW), a classical Chinese medical formulae consisted of Atractylodes
      Rhizome and Fructus Citrus Immaturus, has been commonly used for treatment of
      gastrointestinal diseases. Hesperetin and naringenin are the main components of
      ZZW, and both can alleviate intestinal tract disorders. In this work, plasma
      pharmacokinetics and pharmacodynamics characteristics of ZZW after oral
      administration were investigated using a rapid and sensitive ultra performance
      liquid chromatography-tandem mass spectrometry method with an electrospray
      ionization source in positive ion mode. Biosamples were prepared using methanolic
      precipitation, and the separation of hesperetin and naringenin was achieved on a
      Waters ACQUITY HSS BEH (2.1 mm * 5 mm, 1.7 um) column by linear gradient elution,
      and the total run time was only 3 min. Data were analyzed and estimated using
      WinNonlin Professional version 5.1. With pharmacokinetic analysis, the estimated
      pharmacokinetic parameters (i.e. C(max), area under the concentration-time curve
      (AUC) and t(1/2)), were C(max)  = 776.06 ng/mL, AUC = 9473 ng/mL.h, t1/2 = 5.26 h
      for hesperetin and C(max)  = 2910.6 ng/mL, AUC = 40607.9 ng/mL.h, t1/2 = 4.69 h
      for naringenin, respectively. In the present study, we have also valuated and
      clarified the effect of ZZW on small intestinal movement. It was found that ZZW
      can accelerate intestinal motility in mice and may hold a promising treatment for
      intestinal diseases.

PMID- 23148024
TI  - Metabolically competent human skin models: activation and genotoxicity of
      benzo[a]pyrene.
AB  - The polycyclic aromatic hydrocarbon (PAH) benzo[a]pyrene (BP) is metabolized into
      a complex pattern of BP derivatives, among which the ultimate carcinogen (+)-anti
      BP-7,8-diol-9,10-epoxide (BPDE) is formed to certain extents. Skin is frequently
      in contact with PAHs and data on the metabolic capacity of skin tissue toward
      these compounds are inconclusive. We compared BP metabolism in excised human
      skin, commercially available in vitro 3D skin models and primary 2D skin cell
      cultures, and analyzed the metabolically catalyzed occurrence of seven different
      BP follow-up products by means of liquid chromatography coupled to tandem mass
      spectrometry (LC-MS/MS). All models investigated were competent to metabolize BP,
      and the metabolic profiles generated by ex vivo human skin and skin models were
      remarkably similar. Furthermore, the genotoxicity of BP and its derivatives was
      monitored in these models via comet assays. In a full-thickness skin, equivalent
      BP-mediated genotoxic stress was generated via keratinocytes. Cultured primary
      keratinocytes revealed a level of genotoxicity comparable with that of direct
      exposure to 50-100 nM of BPDE. Our data demonstrate that the metabolic capacity
      of human skin ex vivo, as well as organotypic human 3D skin models toward BP, is
      sufficient to cause significant genotoxic stress and thus cutaneous bioactivation
      may potentially contribute to mutations that ultimately lead to skin cancer.

PMID- 23148025
TI  - Impact of postoperative morbidity on long-term survival after oesophagectomy.
AB  - BACKGROUND: Oesophageal malignancy is a disease with a poor prognosis.
      Oesophagectomy is the mainstay of curative treatment but associated with
      substantial morbidity and mortality. Although mortality rates have improved, the
      incidence of perioperative morbidity remains high. This study assessed the impact
      of postoperative morbidity on long-term outcomes. METHODS: A prospective database
      was designed for patients undergoing oesophagectomy for malignancy from 1998 to
      2011. An observational cohort study was performed with these data, assessing
      intraoperative technical complications, postoperative morbidity and effects on
      overall survival. RESULTS: Some 618 patients were included, with a median follow
      up of 51 months for survivors. The overall complication rate was 64.6 per cent
      (399 of 618), with technical complications in 124 patients (20.1 per cent) and
      medical complications in 339 (54.9 per cent). Technical complications were
      associated with longer duration of surgery (308 min versus 293 min in those with
      no technical complications; P = 0.017), greater operative blood loss (448 versus
      389 ml respectively; P = 0.035) and longer length of stay (22 versus 13 days; P <
      0.001). Medical complications were associated with greater intraoperative blood
      loss (418 ml versus 380 ml in those with no medical complications; P = 0.013) and
      greater length of stay (16 versus 12 days respectively; P < 0.001). Median
      overall and disease-free survival were 41 and 43 months. After controlling for
      age, tumour stage, resection margin, length of tumour, adjuvant therapy,
      procedure type and co-morbidities, there was no effect of postoperative
      complications on disease-specific survival. CONCLUSION: Technical and medical
      complications following oesophagectomy were associated with greater
      intraoperative blood loss and a longer duration of inpatient stay, but did not
      predict disease-specific survival.

PMID- 23148026
TI  - Diagnostic validity across racial and ethnic groups in the assessment of
      adolescent DSM-IV disorders.
AB  - We examine differential validity of the Diagnostic and Statistical Manual of
      Mental Disorders, Fourth Edition (DSM-IV) diagnoses assessed by the fully
      structured Composite International Diagnostic Interview Version 3.0 (CIDI) among
      Latino, non-Latino Black, and non-Latino White adolescents in comparison to gold
      standard diagnoses derived from the Schedule for Affective Disorders and
      Schizophrenia for School-age Children (K-SADS). Results are based on the National
      Comorbidity Survey Replication Adolescent Supplement, a national US survey of
      adolescent mental health. Clinicians re-interviewed 347 adolescent/parent dyads
      with the K-SADS. Sensitivity and/or specificity of CIDI diagnoses varied
      significantly by ethnicity/race for four of ten disorders. Modifications to
      algorithms sometimes reduced bias in prevalence estimates, but at the cost of
      reducing individual-level concordance. These findings document the importance of
      assessing fully-structured diagnostic instruments for differential accuracy in
      ethnic/racial subgroups.

PMID- 23148027
TI  - Disease modelling using induced pluripotent stem cells: status and prospects.
AB  - The ability to convert human somatic cells into induced pluripotent stem cells
      (iPSCs) is allowing the production of custom-tailored cells for drug discovery
      and for the study of disease phenotypes at the cellular and molecular level.
      IPSCs have been derived from patients suffering from a large variety of disorders
      with different severities. In many cases, disease related phenotypes have been
      observed in iPSCs or their lineage-specific progeny. Several proof of concept
      studies have demonstrated that these phenotypes can be reversed in vitro using
      approved drugs. However, several challenges must be overcome to take full
      advantage of this technology. Here, we highlight recent advances in the field and
      discuss the main challenges associated with this technology as it applies to
      disease modelling.

PMID- 23148028
TI  - Hair growth activity of Crataegus pinnatifida on C57BL/6 mouse model.
AB  - Crataegus pinnatifida has a long history of use in traditional oriental herbal
      medicine to stimulating digestion and improving blood circulation. Based on
      nutrition of hair, the present study was conducted to assess the effect of C.
      pinnatifida extract on hair growth using mouse model and its mechanisms of
      action. The C. pinnatifida extract containing the contents of total polyphenol of
      5.88?0.82 g gallic acid/100 g extract and proanthocyanidin of 9.15?1.58 mg
      cyaniding chloride/100 g extract was orally administered daily at a dosage of 50
      mg/kg weight to the 7-week-old C57BL/6 mice in telogen. The C. pinnatifida
      extract promoted hair growth by inducing anagen phase in mice in telogen,
      reflected by color of skin, thickness of hair shaft, and density of hair. The
      ratio of anagento telogen was determined by shape of hair follicles in vertically
      sectioned slide and increased by oral administration of C. pinnatifida extract.
      The number and the size of hair follicles were also enlarged, indicating anagen
      phase induction. The proliferation of human dermal papilla cells (hDPC) was
      accelerated by addition of C. pinnatifida extract, which activated the signaling
      of mitogen-activated protein kinases (Erk, p-38, and JNK) and Akt. Moreover, the
      ratio of Bcl-2/Bax as the determinant of cell fate was also raised in skin. These
      results suggest that the C. pinnatifida extract promotes hair growth by inducing
      anagen phase, which might be mediated by the activation of cellular signalings
      that enhance the survival of cultured hDPC and the increase of the ratio of Bcl-2
      to Bax that protects cells against cell death.

PMID- 23148029
TI  - The Netherlands Obsessive Compulsive Disorder Association (NOCDA) study: design
      and rationale of a longitudinal naturalistic study of the course of OCD and
      clinical characteristics of the sample at baseline.
AB  - In half of Obsessive Compulsive Disorder (OCD) patients the disorder runs a
      chronic course despite treatment. The factors determining this unfavourable
      outcome remain unknown. The Netherlands Obsessive Compulsive Disorder Association
      (NOCDA) study is a multicentre naturalistic cohort study of the biological,
      psychological and social determinants of chronicity in a clinical sample.
      Recruitment of OCD patients took place in mental health organizations. Its design
      is a six-year longitudinal cohort study among a representative clinical sample of
      419 OCD patients. All five measurements within this six-year period involved
      validated semi-structured interviews and self-report questionnaires which
      gathered information on the severity of OCD and its co-morbidity as well as
      information on general wellbeing, quality of life, daily activities, medical
      consumption and key psychological and social factors. The baseline measurements
      also include DNA and blood sampling and data on demographic and personality
      variables. The current paper presents the design and rationale of the study, as
      well as data on baseline sample characteristics. Demographic characteristics and
      co-morbidity ratings in the NOCDA sample closely resemble other OCD study
      samples. Lifetime co-morbid Axis I disorders are present in the majority of OCD
      patients, with high current and lifetime co-morbidity ratings for affective
      disorders (23.4% and 63.7%, respectively) and anxiety disorders other than OCD
      (36% current and 46.5% lifetime).

PMID- 23148030
TI  - Dienamine-mediated inverse-electron-demand hetero-diels-alder reaction by using
      an enantioselective H-bond-directing strategy.
AB  - Giving directions: optically active dihydropyrans bearing three contiguous
      stereogenic centers can be efficiently prepared by the title reaction. High
      stereo- and regiocontrol can be achieved by employing a bifunctional H-bond
      directing aminocatalyst.

PMID- 23148032
TI  - Hypointense hepatocellular nodules on hepatobiliary phase of Gd-EOB-DTPA-enhanced
      MRI: can increasing the flip angle improve conspicuity of lesions?
AB  - PURPOSE: To compare the conspicuity of hypointense hepatocellular nodules in
      patients with chronic liver disease on hepatobiliary phase (HP) of gadolinium
      ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic
      resonance imaging (MRI) acquired with low to high flip angles (FAs). MATERIALS
      AND METHODS: A total of 95 patients with chronic liver disease who underwent Gd
      EOB-DTPA-enhanced MRI were included. HP images were obtained at 20 minutes, with
      15 degrees , 20 degrees , and 30 degrees  FAs. For the detected hepatocellular
      nodule, liver-to-lesion contrast-to-phantom ratios (CPR) and lesion conspicuity
      (LCS) were assessed. RESULTS: In all examinations, 96 hepatocellular nodules
      showing hypointensity on HP were identified. These lesions included 39
      hypovascular nodules and 57 hypervascular nodules. Mean CPR and LCS showed the
      highest value on the 30 degrees  FA, followed by 20 degrees  and 15 degrees  FAs.
      CPR and LCS of 15 degrees  FA were significantly lower than those of 20 degrees 
      and 30 degrees  FAs (P < 0.001 to P = 0.007). CPR of 30 degrees  FA for
      hypervascular nodules was significantly greater than that of 20 degrees  FA (P <
      0.001). CONCLUSION: In the evaluation of hypointense hepatocellular nodules on HP
      of Gd-EOB-DTPA-enhanced MRI, higher FA such as 30 degrees  should be used rather
      than low FA such as 15 degrees .

PMID- 23148031
TI  - Glycyrrhetinic acid exhibits strong inhibitory effects towards UDP
      glucuronosyltransferase (UGT) 1A3 and 2B7.
AB  - The aim of the present study is to evaluate the inhibitory effects of liver UDP
      glucuronosyltransferases (UGTs) by glycyrrhizic acid and glycyrrhetinic acid,
      which are the bioactive ingredients isolated from licorice. The results showed
      that glycyrrhetinic acid exhibited stronger inhibition towards all the tested UGT
      isoforms, indicating that the deglycosylation process played an important role in
      the inhibitory potential towards UGT isoforms. Furthermore, the inhibition
      kinetic type and parameters were determined for the inhibition of glycyrrhetinic
      acid towards UGT1A3 and UGT2B7. Data fitting using Dixon and Lineweaver-Burk
      plots demonstrated that the inhibition of UGT1A3 and UGT2B7 by glycyrrhetinic
      acid was best fit to competitive and noncompetitive type, respectively. The
      second plot using the slopes from Lineweaver-Burk plots versus glycyrrhetinic
      acid concentrations was employed to calculate the inhibition kinetic parameters
      (K(i)), and the values were calculated to be 0.2 and 1.7 MUM for UGT1A3 and
      UGT2B7, respectively. All these results remind us the possibility of UGT
      inhibition-based herb-drug interaction. However, the explanation of these in
      vitro parameters should be paid more caution due to complicated factors,
      including the probe substrate-dependent UGT inhibition behaviour, environmental
      factors affecting the abundance of herbs' ingredients, and individual difference
      of pharmacokinetic factors.

PMID- 23148033
TI  - A luminescent cyclometalated iridium(III) complex accumulates in mitochondria and
      induces mitochondrial shortening by conjugation to specific protein targets.
AB  - We report the cellular properties of a luminescent cyclometalated iridium(III)
      complex, [Ir(pq)(2)(phen-ITC)](PF(6)) (Ir-ITC; Hpq=2-phenylquinoline, phen-ITC=5
      isothiocyanate-1,10-phenanthroline), that efficiently and specifically labels
      mitochondria in living mammalian cells. Ir-ITC can be covalently conjugated to
      its protein targets, and its luminescence survived cell lysis, protein
      extraction, and gel electrophoresis under denaturing conditions. The conjugation
      of Ir-ITC with live-cell proteins is rapid and highly selective; the process
      requires active cellular metabolism, as the conjugation is abolished at
      nonphysiological temperature or in the presence of sodium azide. Based on
      measurements of the luminescence intensity, we have devised a biochemical
      fractionation procedure that allows the enrichment of the conjugated proteins,
      and their subsequent separation by two-dimensional gel electrophoresis (2DGE).
      Luminescent protein spots were picked from the gel and analyzed by mass
      spectrometry; this resulted in the identification of 46 proteins. Many of the
      strongly luminescently labeled proteins are mitochondrial proteins. One of the
      targets is VDAC1 (voltage-dependent anion channel 1). Consistent with known
      phenotypes of VDAC1 deregulation, prolonged exposure of cells to Ir-ITC led to
      significant mitochondrial shortening and fragmentation. As far as we know, this
      is the first report on the molecular characterization of the interactions of a
      luminescent dye with its biological targets. As many biological dyes exhibit
      specific intracellular staining patterns, the identification of their molecular
      targets can help elucidate the mechanisms behind their staining specificities and
      cytotoxicity. We believe our biochemical approach can be applied to identify the
      targets of a wide range of fluorescent and luminescent probes.

PMID- 23148035
TI  - Differences in hydraulic architecture between mesic and xeric Pinus pinaster
      populations at the seedling stage.
AB  - We studied the intraspecific variability of maritime pine in a set of
      morphological and physiological traits: soil-to-leaf hydraulic conductance,
      intrinsic water-use efficiency (WUE, estimated by carbon isotope composition,
      delta(13)C), root morphology, xylem anatomy, growth and carbon allocation
      patterns. The data were collected from Pinus pinaster Aiton seedlings (25 half
      sib families from five populations) grown in a greenhouse and subjected to water
      and water-stress treatments. The aims were to relate this variability to
      differences in water availability at the geographic location of the populations,
      and to study the potential trade-offs among traits. The drought-stressed
      seedlings demonstrated a decrease in hydraulic conductance and root surface area
      and increased WUE and root tip number. The relationships among the growth,
      morphological, anatomical and physiological traits changed with the scale of
      study: within the species, among/within populations. The populations showed a
      highly significant relationship between the percentage reduction in whole-plant
      hydraulic conductance and WUE. The differences among the populations in root
      morphology, whole-plant conductance, carbon allocation, plant growth and WUE were
      significant and consistent with dryness of the site of seed origin. The xeric
      populations exhibited lower growth and a conservative water use, as opposed to
      the fast-growing, less water-use-efficient populations from mesic habitats. The
      xeric and mesic populations, Tamrabta and San Cipriano, respectively, showed the
      most contrasting traits and were clustered in opposite directions along the main
      axis in the canonical discriminant analysis under both the control and drought
      treatments. The results suggest the possibility of selecting the Arenas
      population, which presents a combination of traits that confer increased growth
      and drought resistance.

PMID- 23148034
TI  - In vivo validation of 4D flow MRI for assessing the hemodynamics of portal
      hypertension.
AB  - PURPOSE: To implement and validate in vivo radial 4D flow MRI for quantification
      of blood flow in the hepatic arterial, portal venous, and splanchnic vasculature
      of healthy volunteers and patients with portal hypertension. MATERIALS AND
      METHODS: Seventeen patients with portal hypertension and seven subjects with no
      liver disease were included in this Health Insurance Portability and
      Accountability Act (HIPAA)-compliant and Institutional Review Board (IRB)
      approved study. Exams were conducted at 3T using a 32-channel body coil with
      large volumetric coverage and 1.4 mm isotropic true spatial resolution. Using
      postprocessing software, cut-planes orthogonal to vessels were used to quantify
      flow (L/min) in the hepatic and splanchnic vasculature. RESULTS: Flow
      quantification was successful in all cases. Portal vein and supraceliac aorta
      flow demonstrated high variability among patients. Measurements were validated
      indirectly using internal consistency at three different locations within the
      portal vein (error = 4.2 +/- 3.9%) and conservation of mass at the portal
      confluence (error = 5.9 +/- 2.5%) and portal bifurcation (error = 5.8 +/- 3.1%).
      CONCLUSION: This work demonstrates the feasibility of radial 4D flow MRI to
      quantify flow in the hepatic and splanchnic vasculature. Flow results agreed well
      with data reported in the literature, and conservation of mass provided indirect
      validation of flow quantification. Flow in patients with portal hypertensions
      demonstrated high variability, with patterns and magnitude consistent with the
      hyperdynamic state that commonly occurs in portal hypertension.

PMID- 23148036
TI  - Transcriptional profiling reveals sexual differences of the leaf transcriptomes
      in response to drought stress in Populus yunnanensis.
AB  - Populus yunnanensis Dode., a native dioecious woody plant species in Southwest
      China, plays an important role in commercial forestry and environmental
      protection. In natural habitats, female P. yunnanensis trees are extremely rare
      while males are dominant in population. Our previous physiological studies in the
      species have revealed sex-dependent difference in response to drought stress, and
      females suffer greater negative effects than males. However, the molecular basis
      of sex-related differences during drought stress has been poorly characterized.
      We use the Illumina-Solexa platform to sequence the leaf transcriptomes derived
      from male and female P. yunnanensis trees grown in normal condition and drought
      stress. In total, 22,235 transcripts were identified in this study and 6039 genes
      were differentially expressed (DEGs) during drought stress. Majority of the DEGs
      were identified in males (92%, 5539); thus, males had greater remodeling of the
      leaf transcriptome in response to drought compared with females. Furthermore,
      many genes involved in hormone biosynthesis, photosynthesis and reactive oxygen
      species (ROS) scavenging enzyme system had more transcript changes in males than
      in females during drought stress, while these genes exhibited higher transcript
      alteration in females than in males in normal condition. Quantitative reverse
      transcriptase-polymerase chain reaction (qRT-PCR) analysis of 15 selected genes
      suggested that during drought treatment the up-regulated DEGs had a quicker
      increment in their transcript abundances in females than that in males. The
      sexual differences of gene transcription coincide with the sexual different
      adaptation of P. yunnanensis in the present natural habitats.

PMID- 23148037
TI  - Investigating the relative importance of individual differences on the work
      family interface and the moderating role of boundary preference for segmentation.
AB  - This study examines the relative importance of individual differences in relation
      to perceptions of work-family conflict and facilitation, as well as the
      moderating role of boundary preference for segmentation on these relationships.
      Relative importance analyses, based on a diverse sample of 380 employees from the
      USA, revealed that individual differences were consistently predictive of self
      reported work-family conflict and facilitation. Conscientiousness, neuroticism,
      negative affect and core self-evaluations were consistently related to both
      directions of work-family conflict, whereas agreeableness predicted significant
      variance in family-to-work conflict only. Positive affect and core self
      evaluations were consistently related to both directions of work-family
      facilitation, whereas agreeableness and neuroticism predicted significant
      variance in family-to-work facilitation only. Collectively, individual
      differences explained 25-28% of the variance in work-family conflict (primarily
      predicted by neuroticism and negative affect) and 11-18% of the variance in work
      family facilitation (primarily predicted by positive affect and core self
      evaluations). Moderated regression analyses showed that boundary preference for
      segmentation strengthened many of the relationships between individual
      differences and work-family conflict and facilitation. Implications for
      addressing the nature of work and family are discussed.

PMID- 23148038
TI  - Assessment of intracranial blood flow velocities using a computer controlled
      vasoactive stimulus: a comparison between phase contrast magnetic resonance
      angiography and transcranial Doppler ultrasonography.
AB  - PURPOSE: To compare measurements of blood flow velocity (BFV) and BFV changes in
      the middle cerebral arteries (MCA) acquired from phase contrast magnetic
      resonance angiography (PCMRA) and transcranial Doppler ultrasound (TCD) during
      controlled manipulation of end-tidal partial pressure of carbon dioxide (PetCO2
      ). MATERIALS AND METHODS: In vivo TCD and PCMRA velocity data from the M1 segment
      in the MCA of nine healthy adult volunteers were acquired during precise
      targeting of PetCO2 induced by a computer-controlled gas delivery system. Doppler
      spectra and phase contrast data were processed into time-averaged peak-velocity
      (TAPV) values for comparison. Changes in velocity between baseline and
      hypercapnia were analyzed in terms of velocity-based cerebrovascular reactivity
      (CVR). RESULTS: Good correlation between the pairs of velocity measurements
      acquired from the two modalities were found (rho = 0.81), but Bland-Altman
      analysis indicates a significant bias error. There was relatively weak agreement
      between the pairs of computed CVR values (rho = -0.26). CONCLUSION: Under precise
      PetCO2 control, PCMRA proves to be more consistent than TCD. Despite issues with
      variability, TCD is qualitatively comparable to PCMRA measures of velocity in the
      MCA. However, PCMRA velocity results are better suited for analyses that require
      quantitative values, such as CVR.

PMID- 23148039
TI  - Graphene-like structure of activated anthracites.
AB  - The structure of a series of activated carbons prepared from anthracite by
      chemical activation has been studied using wide-angle x-ray scattering, molecular
      dynamics and Raman spectroscopy. The BET surface areas of the investigated
      samples are in the range 1500-3430 m(2) g(-1) and the average pore sizes vary
      from 0.75 to 1.35 nm. The diffraction measurements were carried out to a maximum
      value of the scattering vector K(max) = 22 A(-1). The obtained diffraction data
      have been converted to a real space representation in the form of the pair
      correlation function. The structure of the studied samples consists of one or two
      graphite-like layers, stacked without spatial correlations. The size of the
      ordered layer region is approximately 24 A. The atomic arrangement within an
      individual layer has been described in terms of paracrystalline ordering, in
      which lattice distortions are propagated proportionally to the square root of
      inter-atomic distances. The paracrystalline structure has been simulated by
      introducing the Stone-Thrower-Wales, mono-vacancy and di-vacancy defects,
      randomly distributed in the network. These defects lead to the formation of a
      defected network with the presence of non-hexagonal rings in which distortion of
      the structure extends outside of a defect region. Computer generated structural
      models have been relaxed at room temperature using the reactive empirical bond
      order potential for intra-layer interactions and the Lennard-Jones potential for
      inter-layer interactions. For such generated models the structure factors and the
      pair correlation functions were computed. A good agreement between the simulation
      results and the experimental data in both reciprocal and real space provides
      evidence for the correctness of the proposed models. The Raman data support the
      validity of these models. Porosity of the activated anthracites is discussed in
      relation to their defective structure.

PMID- 23148042
TI  - Nonlocal tunnel magnetoresistance and thermal rectification effect in a nanoscale
      three-terminal junction.
AB  - We investigate thermally driven electronic transport through a quantum dot (QD)
      coupled to two ferromagnetic leads and one normal-metallic lead. The effect of
      spin accumulation and temperature bias on the tunnel magnetoresistance (TMR) is
      examined. We obtain a nonlocal negative TMR, which also exhibits a rectification
      effect as a function of the QD level modulated by a gate voltage. For a negative
      QD level, the TMR is zero, and the TMR is negative for a positive QD level. This
      effect arises from the interplay of the spin accumulation and thermoelectric
      transport, which detects the sign reversal of spin accumulation in the QD. In
      addition, our system can also be used as a spin current generator.

PMID- 23148040
TI  - Impact of dietary factors and food processing on food allergy.
AB  - Allergic reactions to food can significantly reduce the quality of life and even
      result in life-threatening complications. In addition, the prevalence of food
      allergy has increased in the last decades in industrialized countries and the
      mechanisms underlying (increased) sensitization are still not fully understood.
      It is believed that the development and maintenance of oral tolerance to food
      antigens is a process actively mediated by the immune system and that this
      reaction is essential to inhibit sensitization. Ongoing research indicates that
      different dietary factors also may contribute to immune homeostasis and oral
      tolerance to food and that food processing modulates allergenicity. One of the
      major questions in food allergy research is therefore which impact nutrition and
      food processing may have on allergenicity of food and perhaps on sensitization.
      We summarize in this review the different dietary factors that are believed to
      contribute to induction of oral tolerance and discuss the underlying mechanisms.
      In addition, the functional consequences of allergen modification will be
      emphasized in the second part as severity of allergic reactions and perhaps
      sensitization to food is influenced by structural modifications of food
      allergens.

PMID- 23148041
TI  - Simple Method for evaluating the degree of liver parenchymal enhancement in the
      hepatobiliary phase of gadoxetic acid-enhanced magnetic resonance imaging.
AB  - PURPOSE: To establish a simple method to evaluate the degree of liver parenchymal
      enhancement in the hepatobiliary phase (HP) of gadoxetic acid-enhanced magnetic
      resonance imaging (MRI). MATERIALS AND METHODS: Subjects comprised 75 patients
      with or without chronic liver disease who underwent gadoxetic acid-enhanced MRI
      and indocyanine green retention at 15 minutes (ICG-R15). HP images were used for
      data analysis. In the quantitative evaluation, liver-to-phantom signal intensity
      (SI) ratio (LPR), liver-to-portal vein SI ratio (LPVR), and liver-to-kidney SI
      ratio (LKR) were calculated. In qualitative visual assessment, liver-to-portal
      vein contrast (LPVC) and liver-to-kidney contrast (LKC) were assessed using a 5
      point scale (1, hyperintense; 2, slightly hyperintense; 3, isointense; 4,
      slightly hypointense; 5, hypointense). Statistical evaluations included the
      Spearman's rank correlation test. RESULTS: LPVC and LKC correlated significantly
      with LPR (rho = -0.445, P < 0.001; rho = -0.576, P < 0.001, respectively). LPVC
      and LKC showed significant correlations with LPVR and LKR (rho = -0.659, P <
      0.001; rho = -0.674, P < 0.001, respectively). In addition, LPVC and LKC
      correlated significantly with ICG-R15 (rho = 0.696, P < 0.001; rho = 0.795, P <
      0.001, respectively). CONCLUSION: LPVC and LKC can be used as simple visual
      indicators to objectively assess the degree of liver parenchymal enhancement on
      HP of gadoxetic acid-enhanced MRI.

PMID- 23148043
TI  - Energy transport in a one-dimensional harmonic ternary chain with Ornstein
      Uhlenbeck disorder.
AB  - In this paper  we study a one-dimensional ternary harmonic chain with the mass
      distribution constructed from an Ornstein-Uhlenbeck process. We generate a
      ternary mass disordered distribution by generating the correlated Ornstein
      Uhlenbeck process and mapping it into a sequence of three different values. The
      probability of each value is controlled by a fixed parameter b. We analyze the
      localization aspect of the above model by numerical solution of the Hamilton
      equations and by the transfer matrix formalism. Our results indicate that the
      correlated ternary mass distribution does not promote the appearance of new
      extended modes. In good agreement with previous work, we obtain extended modes
      for b -> infinity; however, we explain in detail the main issue behind this
      apparent localization- delocalization transition. In addition, we obtain the
      energy dynamics for this classical chain.

PMID- 23148044
TI  - Initial experience of 3 tesla apparent diffusion coefficient values in
      differentiating benign and malignant thyroid nodules.
AB  - PURPOSE: To evaluate the role of diffusion-weighted magnetic resonance imaging
      (DWMRI) in differentiating benign and malignant thyroid nodules using a 3 Tesla
      (T) MRI scanner. MATERIALS AND METHODS: Twenty-eight nodules in 25 patients and
      14 healthy control cases were included in the study. DWMRI was acquired with 6 b
      values with a 3T MRI scanner. The apparent diffusion coefficient (ADC) values of
      the nodules were calculated from reconstructed ADC map images and were compared
      with the final histopathological diagnoses. RESULTS: The mean ADC value of the
      benign nodules was 1548 +/- 353.4 (*10(-6) mm(2) /s), and the mean ADC of the
      malignant nodules was 814 +/- 177.12 (*10(-6) mm(2) /s). The normal thyroid
      tissue had a mean ADC value of 1323.43 +/- 210.35 * 10(-6) mm(2) /s (958-1689 *
      10(-6) mm(2) /s) in the healthy control group. The ADC values were significantly
      different among the three groups (P = 0.001). An ADC value of 905 * 10(-6) mm(2)
      /s was determined to be the cutoff value for differentiating benign and malignant
      nodules, with 90% (55.5-98.3) sensitivity and 100% (81.3-100.0) specificity.
      CONCLUSION: This study suggests that the ADC values of nodules measured with a 3T
      MRI scanner could help in differentiating benign thyroid nodules from malignant
      nodules.

PMID- 23148045
TI  - Anti-proliferative effects of physiological concentrations of enterolactone in
      models of prostate tumourigenesis.
AB  - SCOPE: There is evidence that a mammalian lignan, enterolactone (ENL), decreases
      the proliferation rate of prostate cancer cells, although previous studies have
      used concentrations difficult to achieve through dietary modification. We have
      therefore investigated the anti-proliferative effects of ENL in an in vitro model
      of prostate tumourigenesis at concentrations reported to occur in a range of male
      populations. METHODS AND RESULTS: The effects of 0.1 and 1 MUM ENL on three
      markers of viability and proliferation (metabolic activity, growth kinetics, and
      cell cycle progression) were assessed in the RWPE-1, WPE1-NA22, WPE1-NB14, WPE1
      NB11, WPE1-NB26, LNCaP, and PC-3 cell lines over 72 h. Based on these data, we
      quantified the expression levels of 12 genes involved in the control of DNA
      replication initiation using TaqMan real-time PCR in the WPE1-NA22, WPE1-NB14,
      WPE1-NB11, and WPE1-NB26 cell lines. ENL significantly inhibited the abnormal
      proliferation of the WPE1-NB14 and WPE1-NB11 cell lines and appears to be a
      consequence of decreased expression of abnormal chromatin licensing and DNA
      replication factor 1. CONCLUSION: In contrast to previous studies, concentrations
      of ENL that are reported after dietary intervention restrict the proliferation of
      early-stage tumourigenic prostate cell lines by inhibiting the abnormal formation
      of complexes that initiate DNA replication.

PMID- 23148046
TI  - Intraductal papillary mucinous neoplasm penetrating to the stomach, duodenum, and
      jejunum demonstrated on MR cholangiopancreatography with an oral negative
      contrast agent.
AB  - A 65-year-old man was referred to our hospital due to epigastric pain. Abdominal
      enhanced computed tomography (CT) demonstrated marked dilatation of the main
      pancreatic duct (MPD) and communication to the gastric and duodenal lumen was
      suspected. Esophagogastroduodenoscopy (EGD) showed a villous tumor with white
      mucous discharge in the posterior wall of the gastric corpus and duodenal bulb.
      Pathological specimens showed mucin-producing epithelium with nuclear atypia that
      had developed in a papillary form. Based on these findings, we diagnosed
      intraductal papillary mucinous neoplasm (IPMN) arising in the MPD with
      penetration into the gastric and duodenal lumen. Magnetic resonance
      cholangiopancreatography (MRCP) with an oral negative contrast agent (manganese
      chloride tetrahydrate) showed a fistulous tract not only to the stomach and
      duodenum, but also to the jejunum. MRCP demonstrated mucous streaming with
      remarkably high intensity. In this case, an oral negative contrast agent was
      useful to distinguish mucous discharge from gastric fluid, facilitating the
      diagnosis of penetration to the jejunum. This finding was unobtainable by CT or
      EGD. When IPMN penetrating to other organs is suspected, MRCP with an oral
      negative contrast agent may provide important information.

PMID- 23148047
TI  - Pressure-induced superconductivity in Ba0.5Sr0.5Fe2As2.
AB  - High-pressure electrical resistance measurements have been performed on single
      crystal Ba(0.5)Sr(0.5)Fe(2)As(2)   platelets to pressures of 16 GPa and
      temperatures down to 10 K using designer diamond anvils under quasi-hydrostatic
      conditions with an insulating steatite pressure medium. The resistance
      measurements show evidence of pressure-induced superconductivity with an onset
      transition temperature at ~31 K and zero resistance at ~22 K for a pressure of
      3.3 GPa. The transition temperature decreases gradually with increasing pressure
      before completely disappearing for pressures above 12 GPa. The present results
      provide experimental evidence that a solid solution of two 122-type materials, 
      i.e., Ba(1-x)Sr(x)Fe(2)As(2) (0 < x < 1), can also exhibit superconductivity
      under high pressure.

PMID- 23148048
TI  - Vegetables and PUFA-rich plant oil reduce DNA strand breaks in individuals with
      type 2 diabetes.
AB  - SCOPE: Type 2 diabetes is a multifactorial disease associated with increased
      oxidative stress, which may lead to increased DNA damage. The aim of this study
      was to investigate the effect of a healthy diet on DNA oxidation in diabetics and
      nondiabetics. METHODS AND RESULTS: Seventy-six diabetic and 21 nondiabetic
      individuals participated in this study. All subjects received information about
      the benefits of a healthy diet, while subjects randomly assigned to the
      intervention group received additionally 300 g of vegetables and 25 mL PUFA-rich
      plant oil per day. DNA damage in mononuclear cells (Comet Assay), urinary
      excretion of 8-oxo-7-hydro-2'-deoxyguanosine (8-oxodG) and 8-oxo-7,8
      dihydroguanosine (8-oxoGuo) and glycated hemoglobin (HbA1c) were measured at
      baseline, after 4, 8 (end of intervention), and 16 weeks. The intervention with
      vegetables and PUFA-rich oil led to a significant increase in plasma antioxidant
      concentrations. Diabetic individuals of the intervention group showed a
      significant reduction in HbA1c and DNA strand breaks. Levels of HbA1c were also
      improved in diabetics of the information group, but oxidative damage to DNA was
      not altered. Urinary 8-oxodG and 8-oxoGuo excretion remained unchanged in both
      groups. CONCLUSIONS: This study provides evidence that a healthy diet rich in
      antioxidants reduces levels of DNA strand breaks in diabetic individuals.

PMID- 23148049
TI  - Tunneling through superlattices: the effect of anisotropy and kinematic coupling.
AB  - The tunneling of carriers in stratified superlattice systems is analyzed in 
      terms of the constituent effective mass tensor. The focus is on the effects on
      the tunneling which are caused by the side regions of an intervening barrier.
      Depending on the covalency and work function in the constituent layers of a
      superlattice, it is concluded that the kinematics in the regions on either side
      determined by the effective carrier mass and its interference with the band
      offset at heterojunctions leads to either a constructive or a destructive effect
      on the tunneling current. As an example, Si(1-x)Ge(x)/Si and Al(x)Ga(1-x)As/GaAs
      superlattices are demonstrated to reduce the tunneling current at certain
      fractional thicknesses and stoichiometries of the constituent slabs without
      affecting the lateral mobility. The findings show, in general, how manipulation
      of the carrier's effective mass tensor through stoichiometric/structural
      modulation of the heterostructure may be used to control the tunneling current
      through a given potential barrier, given that the characteristic de Broglie
      wavelength exceeds all the constituent dimensions, thus offering a method
      complementary to high-k technologies.

PMID- 23148050
TI  - Responsive helical self-assembly of AgNO3 and melamine through asymmetric
      coordination for Ag nanochain synthesis.
AB  - Responsive nanohelices can be self-assembled via asymmetric coordination bonding
      between AgNO3 and melamine. Silver nanochains composed of nanoparticles can be
      synthesized simply by photo-reduction of the above complex.

PMID- 23148051
TI  - Short TE (7) Li-MRS confirms Bi-exponential lithium T2 relaxation in humans and
      clearly delineates two patient subtypes.
AB  - PURPOSE: (i) To develop an MRS technique to measure (7) Li levels in human brain
      in a reasonable scan time, (ii) to develop a technique to quantify (7) Li T2
      relaxation times as measured from human brain in patients taking lithium for the
      treatment of their bipolar disorder, and (iii) to confirm or refute the presence
      of bi-exponential (7) Li T2 relaxation in human brain. MATERIALS AND METHODS: We
      modified a spin-echo MRS pulse sequence to decrease its minimum echo time. With
      IRB approval, we performed lithium MRS with the modified pulse sequence on 13
      euthymic bipolar patients stable on long-term lithium to treat their disease.
      RESULTS: We were able to achieve a total scan time per sample of 8:20; total scan
      time including imaging, calibration and MRS was approximately 1 h 15 min. We
      observed bi-exponential T2 relaxation in the majority of patients, with an
      average short decay time of 5.3 +/- 1.4 ms and an average long decay time of 68.2
      +/- 10.2 ms. However, in two patients we observed strongly mono-exponential T2
      relaxation with an average decay time of 47.4 +/- 1.3 ms. CONCLUSION: (7) Li
      relaxation patterns may prove useful to distinguish between lithium-responsive
      and lithium nonresponsive bipolar patients.

PMID- 23148052
TI  - Wait times in the emergency department for patients with mental illness.
AB  - BACKGROUND: It has been suggested that patients with mental illness wait longer
      for care than other patients in the emergency department. We determined wait
      times for patients with and without mental health diagnoses during crowded and
      noncrowded periods in the emergency department. METHODS: We conducted a
      population-based retrospective cohort analysis of adults seen in 155 emergency
      departments in Ontario between April 2007 and March 2009. We compared wait times
      and triage scores for patients with mental illness to those for all other
      patients who presented to the emergency department during the study period.
      RESULTS: The patients with mental illness (n = 51 381) received higher priority
      triage scores than other patients, regardless of crowding. The time to assessment
      by a physician was longer overall for patients with mental illness than for other
      patients (median 82, interquartile range [IQR] 41-147 min v. median 75 [IQR 36
      140] min; p < 0.001). The median time from the decision to admit the patient to
      hospital to ward transfer was markedly shorter for patients with mental illness
      than for other patients (median 74 [IQR 15-215] min v. median 152 [IQR 45-605]
      min; p < 0.001). After adjustment for other variables, patients with mental
      illness waited 10 minutes longer to see a physician compared with other patients
      during noncrowded periods (95% confidence interval [CI] 8 to 11), but they waited
      significantly less time than other patients as crowding increased (mild crowding:
      -14 [95% CI -12 to -15] min; moderate crowding: -38 [95% CI -35 to -42] min;
      severe crowding: -48 [95% CI -39 to -56] min; p < 0.001). INTERPRETATION:
      Patients with mental illness were triaged appropriately in Ontario's emergency
      departments. These patients waited less time than other patients to see a
      physician under crowded conditions and only slightly longer under noncrowded
      conditions.

PMID- 23148053
TI  - New oral anticoagulants.

PMID- 23148054
TI  - Reducing all-cause mortality among patients with psychiatric disorders: a
      population-based study.
AB  - BACKGROUND: Among patients with psychiatric disorders, there are 10 times as many
      preventable deaths from physical disorders as there are from suicide. We
      investigated whether compulsory community treatment, such as community treatment
      orders, could reduce all-cause mortality among patients with psychiatric
      disorders. METHODS: We conducted a population-based survival analysis of an
      inception cohort using record linking. The study period extended from November
      1997 to December 2008. The cohort included patients from all community-based and
      inpatient psychiatric services in Western Australia (state population 1.8
      million). We used a 2-stage design of matching and Cox regression to adjust for
      demographic characteristics, previous use of health services, diagnosis and
      length of psychiatric history. We collected data on successive cohorts for each
      year for which community treatment orders were used to measure changes in numbers
      of patients, their characteristics and outcomes. Our primary outcome was 2-year
      all-cause mortality. Our secondary outcomes were 1-and 3-year all-cause
      mortality. RESULTS: The study population included 2958 patients with community
      treatment orders (cases) and 2958 matched controls (i.e., patients with
      psychiatric disorders who had not received a community treatment order). The
      average age for cases and controls was 36.7 years, and 63.7% (3771) of
      participants were men. Schizophrenia and other nonaffective psychoses were the
      most common diagnoses (73.4%) among participants. A total of 492 patients (8.3%)
      died during the study. Cox regression showed that, compared with controls,
      patients with community treatment orders had significantly lower all-cause
      mortality at 1, 2 and 3 years, with an adjusted hazard ratio of 0.62 (95%
      confidence interval 0.45-0.86) at 2 years. The greatest effect was on death from
      physical illnesses such as cancer, cardiovascular disease or diseases of the
      central nervous system. This association disappeared when we adjusted for
      increased outpatient and community contacts with psychiatric services.
      INTERPRETATION: Community treatment orders might reduce mortality among patients
      with psychiatric disorders. This may be partly explained by increased contact
      with health services in the community. However, the effects of uncontrolled
      confounders cannot be excluded.

PMID- 23148055
TI  - More than just evacuation.

PMID- 23148056
TI  - Iodinated contrast-induced thyrotoxicosis.

PMID- 23148057
TI  - Person-first language: laudable cause, horrible prose.

PMID- 23148058
TI  - Person-first language: what it means to be a "person".

PMID- 23148060
TI  - Corticosteroid therapy in acute respiratory distress syndrome.

PMID- 23148061
TI  - The face of an epidemic.

PMID- 23148062
TI  - Doctor gratitude: a framework and practical suggestions.

PMID- 23148063
TI  - Neutron-diffraction evidence for the ferrimagnetic ground state of a molecule
      based magnet with weakly coupled sublattices.
AB  - The diruthenium compound [Ru(2)(O(2)CMe)(4)](3)[Cr(CN)(6)] contains two weakly
      coupled, ferrimagnetically ordered  sublattices occupying the same volume. Due to
      the weak, antiferromagnetic dipolar interaction K(c) ~ 5 * 10(-3) meV between
      sublattices, a small magnetic field H(c) ~ K(c)/MU(B) ~ 800 Oe aligns the
      sublattice moments. Powder neutron-diffraction measurements on a deuterated
      sample confirm an earlier prediction that the sublattice moments are restricted
      by the anisotropy of the diruthenium 'paddle-wheels' to the cubic diagonals.
      Those measurements also suggest that quantum corrections to the ground state are
      significant.

PMID- 23148064
TI  - Comet: an open-source MS/MS sequence database search tool.
AB  - Proteomics research routinely involves identifying peptides and proteins via
      MS/MS sequence database search. Thus the database search engine is an integral
      tool in many proteomics research groups. Here, we introduce the Comet search
      engine to the existing landscape of commercial and open-source database search
      tools. Comet is open source, freely available, and based on one of the original
      sequence database search tools that has been widely used for many years.

PMID- 23148065
TI  - Review: limited evidence suggests mental health literacy interventions may
      improve help-seeking attitudes for depression, anxiety and general psychological
      distress.

PMID- 23148066
TI  - How will reforms to the NHS in England affect mental health services?

PMID- 23148067
TI  - The future of cardiac surgery: find opportunity in change!

PMID- 23148068
TI  - The present and future of thoracic surgery within the European Association for
      Cardio-Thoracic Surgery (EACTS).
AB  - On 10 February 2012, a Strategic Conference was organized by the European
      Association for Cardio-Thoracic Surgery (EACTS) in Windsor during the
      inauguration of the newly acquired EACTS house. In this review, the present and
      future of thoracic surgery are discussed. With the creation of the Thoracic
      Domain, thoracic surgery has been strengthened and made clearly visible within
      the general EACTS structure. A clearly identified thoracic track is provided
      during the Annual Congress. Specific working groups have been created that deal
      with varying topics of thoracic surgery and diseases of the chest. The European
      School of Cardiothoracic Surgery has been restructured, providing not only
      theoretical but also practical education in thoracic surgery. At national and
      international levels, interdisciplinary cooperation is encouraged. Harmonization
      of thoracic training within Europe is necessary to allow better exchange between
      different countries. Guidelines dealing with specific thoracic procedures should
      be further developed. The Thoracic Domain of EACTS will remain a key player in
      promoting thoracic surgery in Europe and internationally, and in providing high
      level scientific output, education and training in thoracic surgery and diseases
      of the chest, which requires continuous, close cooperation between thoracic and
      cardiothoracic surgeons.

PMID- 23148069
TI  - Hands across mountains: a view from Asia.

PMID- 23148070
TI  - EACTS day in the new EACTS House.
AB  - There is no doubt that the European Association for Cardio-Thoracic Surgery is a
      success story. In 2011, we celebrated the 25th anniversary of this professional
      organization. In 2012, we will celebrate the 25th anniversary of the European
      Journal of Cardio-Thoracic Surgery. In addition, two other journals have been
      initiated, Interactive CardioVascular and Thoracic Surgery and the Multimedia
      Manual of Cardio-Thoracic Surgery, and all of them can be accessed through CTSnet
      (www.ctsnet.org). The most recent development was the birth of EACTS House, and
      it was to celebrate the official opening of EACTS House on 10 February 2011, that
      we held the second Strategic meeting, 'EACTS in the Future'. On this occasion,
      the EACTS council and delegates of the EACTS Domains (Domain of Thoracic Disease,
      Domain of Vascular Disease, Domain of Congenital Cardiac Disease and Domain of
      Adult Cardiac Disease) came together with representative thoracic and cardio
      vascular surgeons from North America, Asia and BRICS countries as well as senior
      managers from industry in order to decide where to go from there. As a basis for
      starting the discussions, a sector analysis of the activities of the Department
      of Cardio-Vascular Surgery at CHUV in Lausanne, Switzerland was performed in
      order to identify the trends in the activities of our group of surgeons by
      pulling the consolidated data for the period running from 1 January 1995 to 31
      December 2010. Interestingly enough, the most frequent procedures like coronary
      artery bypass graft and valve repair/replacement did not increase despite a
      growing programme. In our setting, the compensation came mainly from vascular
      surgery and mechanical circulatory support. These data have to be put in
      perspective by the reports provided by the EACTS domain chairs in order to
      identify the challenges and opportunities for the future development of our
      specialties.

PMID- 23148071
TI  - The view from the interventionalist.
AB  - The development of percutaneous valve replacement has broadened the procedural
      interface between interventional cardiologists and their cardiothoracic surgical
      colleagues. Our relationship is no longer restricted to the arena of coronary
      artery disease, and opportunities now exist to share the care of large numbers of
      high surgical risk patients with severe aortic stenosis. These complex
      professional relationships have a mutual dependence and many shared objectives
      that should be centred upon the optimal care of cardiac patients. However, the
      continuing evolution of technology demands that these relationships evolve with
      time. A failure to understand this need for mutual change and increased
      cooperation has previously led to a sense of competition and Departmental
      separation between cardiac intervention and surgery. These fractured
      relationships ultimately limit the quality of care that we deliver to our
      patients.

PMID- 23148072
TI  - The future of aortic surgery in Europe.
AB  - At least every ten years, each specialty should reflect upon its past, its
      present and its future, in order to be able to reconfirm the direction in which
      it is headed, to adopt suggestions from inside and outside and, consequently, to
      improve. As such, the aim of this manuscript is to provide the interested reader
      with an overview of how aortic surgery and (perhaps more accurately) aortic
      medicine has evolved in Europe, and its present standing; also to provide a
      glimpse into the future, trying to disseminate the thoughts of a group of people
      actively involved in the development of aortic medicine in Europe, namely the
      Vascular Domain of the European Association of Cardio-Thoracic Surgery (EACTS).

PMID- 23148073
TI  - EACTS in the future: second strategic conference. The view from the BRICS
      countries.
AB  - BRICS is an acronym for Brazil, Russia, India, China and South Africa and has
      emerged as the symbol of the shift in global economic power, developing at a
      faster pace than industrialized countries. BRICS accounted for 53% of the entire
      global GDP growth during the period 2007-2010 and, in the next 40 years, as much
      as 80% of the world's economic growth will come from emerging market countries.
      Despite the fact that infrastructure in BRICS has improved markedly in recent
      years, these countries have not created a modern, broad healthcare system as
      encountered in the G7 industrialized countries and extensive regional differences
      in health expenditure exist between them. Nevertheless, the BRICS countries are
      quickly taking the lead in encouraging innovation, simplifying devices and
      processes and applying newer technologies that are more adapted to consumers'
      needs and less costly. Cardiovascular surgery in the BRICS countries remains far
      lower when compared with the G7 countries and the cardiovascular surgical
      training also varies widely. However, this huge shift in the global economy and
      the regional discrepancies might represent a unique opportunity for co-operation,
      interaction and partnership to integrate cardiovascular societies and surgeons
      all over the globe for the best care of our patients: surely it will contribute
      to making our world more egalitarian, fairer and better.

PMID- 23148074
TI  - The North American view: the perspective of the American Association for Thoracic
      Surgeons.
AB  - The American Association for Thoracic Surgeons (AATS) is a small, selective
      organization focused on scholarship in thoracic surgery, complementing the
      Society of Thoracic Surgeon's focus on practice issues impacting all practicing
      surgeons. AATS works to improve the academic quality of North American and
      International meetings and symposia and focuses specific lobbying efforts on
      improving National Institutes of Health funding for thoracic surgeons. We need to
      embrace new technologies and incorporate them into our training programmes, and
      to cultivate the creativity necessary for innovation. It is necessary to make
      residents and medical students more aware of the virtues of a career in our
      specialty and focus less on making the training process more attractive for its
      own sake.

PMID- 23148075
TI  - The acquired cardiac disease domain: the next 5 years.
AB  - At a recent in-house meeting at the European Association for Cardiothoracic
      Surgery (EACTS) headquarters in Windsor, the Chairs of the four domains were
      asked by the President to present their perception of the next 5 years in their
      respective domains. This review represents a distillation of our discussions on
      adult cardiac surgery. Advances in technology and imaging are having a radical
      effect on the working lives of surgeons. In clinical practice, the growth of
      heart teams and the breaking down of artificial barriers between specialities are
      altering the way we practice for the better. We see the development of hybrid
      approaches to many areas such as coronary artery surgery and operations on the
      thoracic aorta. These changes require careful analysis to ensure that they
      produce better outcomes that are also cost-effective. All health-care systems are
      at breaking point, and it is our responsibility to harness new technology to
      benefit our patients. This is all part of placing the patient at the centre of
      our activities. Hence, we see the involvement of patients in the design and
      analysis of clinical trials, which also require great mutual trust and
      cooperation between surgeons in different countries. Because of the dramatic
      changes in the pattern of working, we have had to alter our patterns of training
      and education, and we will continue to make significant innovations in the
      future. These are exciting challenges that will keep us all busy for the next 5
      years at least.

PMID- 23148076
TI  - The future of cardiothoracic surgery: a view from North America.
AB  - Cardiothoracic surgery is undergoing major changes related to evolving
      technology, changes in the educational paradigm and evolution of health care
      policy. Many see these changes as a threat to the stature and viability of
      cardiothoracic surgery. However, these changes create tremendous opportunity to
      broaden our skills and scope of practice, as well as to better prepare the next
      generation of cardiothoracic surgeons for a successful career in helping patients
      with cardiothoracic disease.

PMID- 23148078
TI  - Differential mobility of pigment-protein complexes in granal and agranal
      thylakoid membranes of C3 and C4 plants.
AB  - The photosynthetic performance of plants is crucially dependent on the mobility
      of the molecular complexes that catalyze the conversion of sunlight to metabolic
      energy equivalents in the thylakoid membrane network inside chloroplasts. The
      role of the extensive folding of thylakoid membranes leading to structural
      differentiation into stacked grana regions and unstacked stroma lamellae for
      diffusion-based processes of the photosynthetic machinery is poorly understood.
      This study examines, to our knowledge for the first time, the mobility of
      photosynthetic pigment-protein complexes in unstacked thylakoid regions in the C3
      plant Arabidopsis (Arabidopsis thaliana) and agranal bundle sheath chloroplasts
      of the C4 plants sorghum (Sorghum bicolor) and maize (Zea mays) by the
      fluorescence recovery after photobleaching technique. In unstacked thylakoid
      membranes, more than 50% of the protein complexes are mobile, whereas this number
      drops to about 20% in stacked grana regions. The higher molecular mobility in
      unstacked thylakoid regions is explained by a lower protein-packing density
      compared with stacked grana regions. It is postulated that thylakoid membrane
      stacking to form grana leads to protein crowding that impedes lateral diffusion
      processes but is required for efficient light harvesting of the modularly
      organized photosystem II and its light-harvesting antenna system. In contrast,
      the arrangement of the photosystem I light-harvesting complex I in separate units
      in unstacked thylakoid membranes does not require dense protein packing, which is
      advantageous for protein diffusion.

PMID- 23148079
TI  - An essential role for tomato sulfite oxidase and enzymes of the sulfite network
      in maintaining leaf sulfite homeostasis.
AB  - Little is known about the homeostasis of sulfite levels, a cytotoxic by-product
      of plant sulfur turnover. By employing extended dark to induce catabolic
      pathways, we followed key elements of the sulfite network enzymes that include
      adenosine-5'-phosphosulfate reductase and the sulfite scavengers sulfite oxidase
      (SO), sulfite reductase, UDP-sulfoquinovose synthase, and beta-mercaptopyruvate
      sulfurtransferases. During extended dark, SO was enhanced in tomato (Solanum
      lycopersicum) wild-type leaves, while the other sulfite network components were
      down-regulated. SO RNA interference plants lacking SO activity accumulated
      sulfite, resulting in leaf damage and mortality. Exogenous sulfite application
      induced up-regulation of the sulfite scavenger activities in dark-stressed or
      unstressed wild-type plants, while expression of the sulfite producer, adenosine
      5'-phosphosulfate reductase, was down-regulated. Unstressed or dark-stressed wild
      type plants were resistant to sulfite applications, but SO RNA interference
      plants showed sensitivity and overaccumulation of sulfite. Hence, under extended
      dark stress, SO activity is necessary to cope with rising endogenous sulfite
      levels. However, under nonstressed conditions, the sulfite network can control
      sulfite levels in the absence of SO activity. The novel evidence provided by the
      synchronous dark-induced turnover of sulfur-containing compounds, augmented by
      exogenous sulfite applications, underlines the role of SO and other sulfite
      network components in maintaining sulfite homeostasis, where sulfite appears to
      act as an orchestrating signal molecule.

PMID- 23148081
TI  - Incremental value of CT perfusion in the diagnosis of coronary artery disease.

PMID- 23148080
TI  - The rubisco small subunit is involved in tobamovirus movement and Tm-22-mediated
      extreme resistance.
AB  - The multifunctional movement protein (MP) of Tomato mosaic tobamovirus (ToMV) is
      involved in viral cell-to-cell movement, symptom development, and resistance gene
      recognition. However, it remains to be elucidated how ToMV MP plays such diverse
      roles in plants. Here, we show that ToMV MP interacts with the Rubisco small
      subunit (RbCS) of Nicotiana benthamiana in vitro and in vivo. In susceptible N.
      benthamiana plants, silencing of NbRbCS enabled ToMV to induce necrosis in
      inoculated leaves, thus enhancing virus local infectivity. However, the
      development of systemic viral symptoms was delayed. In transgenic N. benthamiana
      plants harboring Tobacco mosaic virus resistance-22 (Tm-22), which mediates
      extreme resistance to ToMV, silencing of NbRbCS compromised Tm-22-dependent
      resistance. ToMV was able to establish efficient local infection but was not able
      to move systemically. These findings suggest that NbRbCS plays a vital role in
      tobamovirus movement and plant antiviral defenses.

PMID- 23148083
TI  - Budd-Chiari syndrome complicating the surgical closure of patent foramen ovale in
      right minithoracotomy.
AB  - We present the case of a 45-year old female operated on for minimally invasive
      closure of patent foramen ovale, who suffered in the postoperative course of the
      Budd-Chiari syndrome caused by the thrombotic occlusion of the inferior vena
      cava. Medical treatment with oral anticoagulants and heparin was promptly
      established, avoiding a further increase of the thrombus that completely
      disappeared 3 months later.

PMID- 23148082
TI  - Layer-specific analysis of myocardial deformation for assessment of infarct
      transmurality: comparison of strain-encoded cardiovascular magnetic resonance
      with 2D speckle tracking echocardiography.
AB  - AIMS: Separate analysis of endocardial and epicardial myocardial layer
      deformation has become possible using strain-encoded cardiovascular magnetic
      resonance (SENC) and 2D-dimensional speckle tracking echocardiography (Echo).
      This study evaluated and compared both modalities for the assessment of infarct
      transmurality as defined by late gadolinium enhancement (LGE) cardiovascular
      magnetic resonance (CMR). METHODS AND RESULTS: In 29 patients (age 62.4 +/- 11.7
      years, 23 male) with ischaemic cardiomyopathy, SENC using 1.5 T CMR and Echo were
      performed. Peak circumferential systolic strain of the endocardial and the
      epicardial layer of 304 myocardial segments was assessed by SENC and by Echo. The
      segmental transmurality of myocardial infarction was determined as relative
      amount of LGE (0%: no infarction; 1-50%: non-transmural infarction; 51-100%:
      transmural infarction). Endocardial and epicardial strain defined by SENC and by
      Echo differed significantly between segments of different infarct transmurality
      determined by CMR. Endocardial layer circumferential strain analysis by Echo and
      by SENC allowed distinction of segments with non-transmural infarction from non
      infarcted segments with similar accuracy [area under the curve (AUC) 0.699 vs.
      0.649, respectively, P = 0.239]. Epicardial layer circumferential strain analysis
      by Echo and by SENC allowed distinction of transmural from non-transmural
      myocardial infarction defined by LGE CMR with similar accuracy (AUC 0.721 vs.
      0.664, respectively, P = 0.401). Endocardial strain by SENC correlated moderately
      with endocardial strain by Echo (r = 0.50; standard error of estimate = 5.2%).
      CONCLUSION: Layer-specific analysis of myocardial deformation by Echo and by SENC
      allows discrimination between different transmurality categories of myocardial
      infarction with similar accuracy. However, accuracy of both methods is non
      optimal, indicating that further tools for improvement should be evaluated in the
      future.

PMID- 23148084
TI  - Cognitive function after transapical aortic valve implantation: a single-centre
      study with 3-month follow-up.
AB  - OBJECTIVES: Reports on adverse neurological events following transcatheter aortic
      valve implantation (TAVI) have focused on strokes, while more subtle
      postoperative cognitive decline has not yet been systematically investigated. In
      this study, we prospectively examined neurological and cognitive outcomes in
      patients undergoing transapical (TA) and surgical aortic valve replacement (AVR).
      METHODS: A total of 64 patients with severe symptomatic aortic stenosis were
      investigated between January 2008 and July 2009. Clinical neurological
      examination and comprehensive neuropsychological testing were performed before
      and after the procedure, at discharge and at 3-month follow-up. Diffusion
      weighted magnetic resonance imaging (DW-MRI) was applied to detect morphological
      brain injury. RESULTS: TA-TAVI patients (n = 27) were older and at higher
      surgical risk compared with surgical AVR patients (n = 37; mean age 82.2 +/- 4.7
      vs 67.5 +/- 8.9 years; log EuroSCORE 36.4 +/- 13.2 vs 2.6 +/- 8.5%, both P
      <0.001). There was one stroke in each group (3.7 vs 2.7%, P = 0.49), both
      classified as embolic based on imaging characteristics. After TA-TAVI, cognitive
      tests showed no decline during follow-up, while, after AVR, 7 of 11 tests showed
      a decline early after surgery. Similarly, with-in patient analysis showed that
      the rate of individuals with clinically relevant cognitive decline was increased
      early after AVR (TA-TAVI vs AVR: 18 vs 46% at discharge [P = 0.03]; 28 vs 6% at 3
      months [P = 0.04]). New focal ischaemic cerebral lesions were detected on DW-MRI
      in 58% (7 of 12) of patients after TA-TAVI vs 34% (12 of 35) after AVR (P =
      0.13). The number of brain lesions per patient and cumulative embolic load per
      patient were similar between groups. An association between postoperative
      cerebral ischaemia and cognitive dysfunction was not found (odds ratio 2.37, 95%
      confidence interval 0.05-113.75, P = 0.66). CONCLUSIONS: Cognitive function was
      only mildly impaired after TA-TAVI when compared with a marked, albeit transient,
      decline after surgical AVR. Focal embolic brain injury tended to occur more
      frequently after TA-TAVI, but this was not related to cognitive decline during
      the 3-month follow-up.

PMID- 23148085
TI  - Sex selection of sperm in farm animals: status report and developmental
      prospects.
AB  - Pre-selection of spermatozoa based on the relative DNA difference between X- and
      Y-chromosome bearing populations by flow cytometry is an established method that
      has been introduced into commercial cattle production. Although several important
      improvements have increased the sort efficiency, the fertilising ability of sexed
      spermatozoa based on offspring per insemination is still behind farmers'
      expectations. The main stress factors, especially on mitochondria, that reduce
      the lifespan of spermatozoa are described, and new technical as well as
      biological solutions to maintain the natural sperm integrity and to increase the
      sorting efficiency are discussed. Among these methods are the identification of Y
      chromosome bearing spermatozoa by bi-functionalised gold nanoparticles and
      triplex hybridisation in vivo as well as new laser-controlled deflection system
      that replaces the deflection of spermatozoa in the electrostatic field.
      Additionally, as well as a new nonsurgical transfer system of spermatozoa into
      the oviduct of cows has been developed and allows a significant reduction of
      spermatozoa per transfer. Altogether, the improvements made in the recent years
      will allow a broader use of sex-sorted spermatozoa even in those species that
      require more cells than cows and sheep.

PMID- 23148086
TI  - Anastrozole and celecoxib for endometriosis treatment, good to keep them apart?
AB  - Endometriosis is a benign gynecological disease. Cyclooxygenase-2 (COX-2) and
      aromatase proteins have been shown to be overexpressed in eutopic endometrium
      from women suffering from this disease compared to disease-free women.
      Furthermore, inhibition of these molecules individually was demonstrated to have
      antiproliferative and proapoptotic effects both in vitro and in vivo in several
      models. In this study, the effect of combining celecoxib, a selective COX-2
      inhibitor, and anastrozole, an aromatase inhibitor, on the implantation and
      growth of endometriotic like lesions in a murine model of endometriosis was
      evaluated. Endometriosis was surgically induced in female BALB/c mice. After 28
      days of treatment with celecoxib, anastrozole, or their combination, animals were
      killed and lesions were counted, measured, excised, and fixed.
      Immunohistochemistry for proliferating cell nuclear antigen and CD34 was
      performed for assessment of cell proliferation and vascularization. TUNEL
      technique was performed for apoptosis evaluation. Celecoxib was the only
      treatment to significantly reduce the number of lesions established per mouse,
      their size and vascularized area. In addition, cell proliferation was
      significantly diminished and apoptosis was significantly enhanced by both
      individual treatments. When the therapies were combined, they reversed their
      effects. These results confirm that celecoxib and anastrozole separately decrease
      endometriotic growth, but when combined they might have antagonizing effects.

PMID- 23148087
TI  - Tumour necrosis factor-alpha is the signal induced by mating to shutdown a 2
      methoxyestradiol nongenomic action necessary to accelerate oviductal egg
      transport in the rat.
AB  - Mating shut down a 2-methoxyestradiol (2ME) nongenomic action necessary to
      accelerate egg transport in the rat oviduct. Herein, we investigated whether
      tumour necrosis factor-alpha (TNF-alpha) participates in this mating effect. In
      unmated and mated rats, we determined the concentration of TNF-alpha in the
      oviductal fluid and the level of the mRNA for Tnf-a (Tnf) and their receptors
      Tnfrsf1a and Tnfrsf1b in the oviduct tissues. The distribution of the TNFRSF1A
      and TNFRSF1B proteins in the oviduct of unmated and mated was also assessed.
      Finally, we examined whether 2ME accelerates oviductal egg transport in unmated
      rats that were previously treated with a rat recombinant TNF-alpha alone or
      concomitant with a selective inhibitor of the NF-kappaB activity. Mating
      increased TNF-alpha in the oviductal fluid, but Tnf transcript was not detected
      in the oviduct. The mRNA for TNF-alpha receptors as well as their distribution
      was not affected by mating, although they were mainly localized in the
      endosalpinx. Administration of TNF-alpha into the oviduct of unmated rats
      prevented the effect of 2ME on egg transport. However, the NF-kappaB activity
      inhibitor did not revert this effect of TNF-alpha. These results indicate that
      mating increased TNF-alpha in the oviductal fluid, although this not associated
      with changes in the expression and localization of TNF-alpha receptors in the
      oviductal cells. Furthermore, TNF-alpha mimicked the effect of mating on the 2ME
      induced egg transport acceleration, independently of the activation of NF-kappaB
      in the oviduct. We concluded that TNF-alpha is the signal induced by mating to
      shut down a 2ME nongenomic action in the rat oviduct.

PMID- 23148088
TI  - Intron-derived aberrant splicing of A20 transcript in rheumatoid arthritis.
AB  - OBJECTIVE: Aberrant splicing is one of the most significant components generating
      functional diversity in many pathological conditions. The objective of this study
      was to analyse the mutations or aberrant splicing of A20 transcript, the region
      encompassing the ovarian tumour (OTU) domain [which is functionally important as
      an inhibitor of nuclear factor (NF)-kappaB activation] in fibroblast-like
      synoviocytes (FLSs) from RA patients. METHODS: Alterations in A20 transcripts
      were determined through sequence analysis of 10 clones of A20 cDNA in FLSs from
      each of the five RA patients. The levels of aberrant A20 transcript were measured
      by quantitative real-time RT-PCR with primers to specifically recognize the
      inserted introns. The functional role of A20 and its aberrant variants were
      examined by analysing NF-kappaB luciferase reporter activity and NF-kappaB
      dependent target gene expression. RESULTS: In RA FLSs, we discovered four novel
      aberrant A20 transcripts, most of which resulted from insertion of partial intron
      2, intron 4 and/or deletion of exon 4. In each of these FLSs, sequence analysis
      revealed that these aberrant insertional sequences were flanked by consensus
      splice donor and acceptor sequences without nucleotide substitution, suggesting
      alternative splicing as the likely mutational mechanism. These variants elicited
      a codon frame shift by creating a premature translational stop codon, and
      eventually, disruption of the OTU domain (which is functionally important as an
      inhibitor of NF-kappaB activation) of A20. The expression level of aberrant A20
      transcript was correlated well with persisitently enhanced status of NF-kappaB
      signalling, as evident by the phosphorylation of inhibitor of NF-kappaB (IkappaB)
      alpha and transcription of NF-kappaB target genes. CONCLUSION: The results
      suggest that A20 inactivation by the novel aberrant splicing may contribute to RA
      progression by inducing persistent NF-kappaB activation.

PMID- 23148089
TI  - Factors limiting participation in arthritis self-management programmes: an
      exploration of barriers and patient preferences within a randomized controlled
      trial.
AB  - OBJECTIVE: To improve understanding of barriers to participation in community
      based arthritis self-management programmes and patient preferences for self
      management education. METHODS: Individuals with hip or knee OA referred to
      orthopaedic surgeons or rheumatologists at six public and private hospitals in
      Victoria, Australia, were recruited for a randomized controlled trial (RCT) of
      the Stanford Arthritis Self-Management Programme (ASMP). As part of the study
      design, potential participants were asked during the screening and recruitment
      process about reasons for being unable to attend the course, reasons for not
      participating in the study and individual preferences for course scheduling.
      RESULTS: Of 1125 individuals assessed, 216 (19%) were unable to attend six ASMP
      sessions. This was commonly due to physical limitations, including illness,
      restricted mobility and pain (22%), difficulty getting to or from courses (22%),
      work commitments (22%), the time commitment required (17%) and family roles
      (12%). Among those who did not want to participate in the study (n = 258), the
      overwhelming reason was disinterest (74%). Specific preferences for course
      scheduling were frequent, confirming the practical challenges faced in organizing
      courses for the RCT. CONCLUSION: Incorporating patients from public and private
      settings, this study has elicited new insights into barriers to ASMP
      participation. Many people with hip or knee OA have limited capacity and
      motivation to attend community-based group programmes. Future self-management
      programmes and research should include more accessible options for those who
      cannot attend group-based programmes. Trial registration. Australian New Zealand
      Clinical Trials Registry, http://www.anzctr.org.au/, ACTRN12606000174583.

PMID- 23148090
TI  - Long-term data on corticosteroids and mycophenolate mofetil treatment in lupus
      nephritis.
AB  - OBJECTIVE: We investigated the long-term outcome of patients with proliferative
      LN treated with CSs and MMF. METHODS: This was a single-centre retrospective
      study on patients with biopsy-proven class III/IV +/- V LN treated with
      prednisolone and MMF continuously as both early and maintenance
      immunosuppression. RESULTS: Sixty-five patients were included, and followed for
      91.9 (47.7) months. All received prednisolone and MMF as induction
      immunosuppression. In 31 patients, maintenance immunosuppression comprised
      prednisolone and MMF only (MMF-MMF group). MMF was replaced with AZA in 23
      patients (MMF-AZA), and with calcineurin inhibitors (CNIs) in 11 patients (MMF
      CNI) at sometime during follow-up. Ten-year patient and renal survival rates were
      91% and 86%, respectively, and were similar in the three groups. MMF-MMF group
      showed better relapse-free survival than MMF-AZA and MMF-CNI patients (76% vs 56%
      vs 43%, respectively at 5 years; 69% vs 32% vs 0%, respectively at 10 years; MMF
      MMF vs MMF-AZA or MMF-CNI, P = 0.049 or 0.019, respectively; MMF-AZA vs MMF-CNI,
      P = 0.490). Patients treated with MMF for >24 months had better relapse-free
      survival than those treated for shorter durations (88% vs 48% at 5 years; 81% vs
      28% at 10 years; P < 0.001). Renal function at 10 years was better in the MMF-MMF
      group. Anaemia was associated with MMF treatment. Other adverse events were
      comparable and relatively minor with MMF, AZA or CNI as maintenance. CONCLUSION:
      Long-term treatment with CSs and MMF from induction to maintenance phase is
      associated with relatively favourable long-term outcome in Chinese LN patients.
      Discontinuation of MMF before 24 months may increase the risk of flares.

PMID- 23148091
TI  - Interaction between oxidative stress and smoking is associated with an increased
      risk of rheumatoid arthritis: a case-control study.
AB  - OBJECTIVE: To investigate the relationship between oxidative stress and smoking
      and development of RA. METHODS: A case-control study was conducted in treatment
      naive early-onset RA patients and healthy controls, matched by age, gender and
      current smoking habit. Plasma lipid hydroperoxides (LOOH), carbonyl protein (CP)
      and malonyldialdehyde (MDA) levels were measured to estimate oxidative stress.
      Smoking exposure was quantified in pack-years. The presence of an interaction
      between oxidative stress and smoking exposure was investigated using three
      measures of additive interaction: relative excess risk due to the interaction
      (RERI), attributable proportion due to the interaction (AP) and the synergy index
      (S). RESULTS: A total of 65 RA patients and 65 healthy controls were included.
      Statistically significant differences were observed in RA-related variables, age,
      BMI and smoking dose between cases and controls. Plasma LOOH and CP levels were
      associated with RA risk, which was more prominent for LOOH levels >27.9 uM [odds
      ratio (OR) 18.8] and CP levels >64.3 uM (OR 24.9). A reverse association was
      observed between MDA levels and RA risk, OR 6.4 for MDA levels <8.5 uM. Having
      >20 pack-years increased risk for RA with an OR of 19.7. The interaction between
      smoking and oxidative stress increased RA risk significantly, and RERI between
      LOOH, CP or MDA and smoke exposure were 8.2, 5.0 and 51.5, respectively.
      CONCLUSION: These data suggest that the interaction between oxidative stress and
      smoking increases RA risk.

PMID- 23148092
TI  - Survival of lupus patients on dialysis: a Brazilian cohort.
AB  - OBJECTIVE: Data about the survival rate of lupus patients on dialysis is
      controversial. The objective of this controlled prospective study was to report
      the survival of SLE patients undergoing dialysis and to analyse factors
      associated with mortality. METHODS: Twenty dialysis centres were visited between
      May 2003 and February 2004. Disease activity was evaluated using the SLEDAI
      without the renal-related parameters [non-renal (nr)SLEDAI] data collection was
      performed at entrance to the study. The control group consisted of haemodialysis
      patients without SLE matched for gender, age, dialysis modality, time on dialysis
      and dialysis-associated HCV infection. Patients were prospectively followed for
      60 months. The Kaplan-Meier method was used to estimate survival. Associations of
      risk factors with mortality were tested using the Cox proportional hazards model.
      RESULTS: Each group was composed of 57 patients. In the multivariate analysis,
      only nrSLEDAI > 8 [hazard ratio (HR) 6.368; 95% CI 1.798, 22.548; P = 0.004], and
      urea reduction ratio (HR 0.953; 95% CI 0.917, 0.990; P = 0.014) were
      independently associated with mortality in lupus patients. The 5-year survival
      rate of the control group and the one from SLE patients with nrSLEDAI <= 8 (n =
      51) were similar (83% and 73%, respectively) but significantly better than the
      one for SLE patients with nrSLEDAI > 8 (n = 6, 17%), P < 0.001. CONCLUSION: A
      high nrSLEDAI was strongly associated with 5-year mortality in lupus patients on
      dialysis.

PMID- 23148094
TI  - Cauliform bacteria lacking phospholipids from an abyssal hydrothermal vent:
      proposal of Glycocaulis abyssi gen. nov., sp. nov., belonging to the family
      Hyphomonadaceae.
AB  - Cauliform bacteria are prosthecate bacteria often specialized for oligotrophic
      environments. A polyphasic approach, comprising 16S rRNA gene sequencing, lipid
      analysis and salt tolerance characterizations, was used to clarify the taxonomy
      of one isolate, strain MCS 33(T), obtained from above the hot water plume of a
      deep-sea hydrothermal vent near Vancouver island, Canada. Cells contained no
      detectable phospholipids or sulpholipids, but did contain 1,2-di-O-acyl-3-O-alpha
      D-glucopyranosylglycerol, 1,2-di-O-acyl-3-O-alpha-D-glucopyranuronosylglycerol
      and the novel lipid 1,2-di-O-acyl-3-[O-alpha-D-glucopyranuronosyl]glycerol-6'-N
      glycine. It is assumed that the various glucoronosyl lipids are replacing, at
      least partially, the phospholipids in their various tasks in the cell cycle. The
      G+C content of the genomic DNA of strain MCS 33(T) was 62.8 mol%, and Q10 was the
      predominant respiratory ubiquinone. The 16S rRNA gene sequence of this
      chemoheterotrophic, aerobic, moderately halophilic strain showed only a low
      similarity of 94.4% to that of Oceanicaulis alexandrii C116-18(T), and both
      strains also differed based on their lipids. Although the novel strain was
      isolated from seawater sampled near a hydrothermal vent, its optimum temperature
      for growth was 30  degrees C. The main cellular fatty acids were C18:1omega7c,
      C18:0 and the unknown fatty acid ECL 11.798, and the main hydroxy fatty acid was
      C12:0 3-OH. The strain is proposed to represent a novel species of a new genus,
      Glycocaulis abyssi gen. nov., sp. nov. The type strain of the type species is MCS
      33(T) (=LMG 27140(T)=CCUG 62981(T)).

PMID- 23148093
TI  - The association of a La module with the PABP-interacting motif PAM2 is a
      recurrent evolutionary process that led to the neofunctionalization of La-related
      proteins.
AB  - La-related proteins (LARPs) are largely uncharacterized factors, well conserved
      throughout evolution. Recent reports on the function of human LARP4 and LARP6
      suggest that these proteins fulfill key functions in mRNA metabolism and/or
      translation. We report here a detailed evolutionary history of the LARP4 and 6
      families in eukaryotes. Genes coding for LARP4 and 6 were duplicated in the
      common ancestor of the vertebrate lineage, but one LARP6 gene was subsequently
      lost in the common ancestor of the eutherian lineage. The LARP6 gene was also
      independently duplicated several times in the vascular plant lineage. We observed
      that vertebrate LARP4 and plant LARP6 duplication events were correlated with the
      acquisition of a PABP-interacting motif 2 (PAM2) and with a significant
      reorganization of their RNA-binding modules. Using isothermal titration
      calorimetry (ITC) and immunoprecipitation methods, we show that the two plant
      PAM2-containing LARP6s (LARP6b and c) can, indeed, interact with the major plant
      poly(A)-binding protein (PAB2), while the third plant LARP6 (LARP6a) is unable to
      do so. We also analyzed the RNA-binding properties and the subcellular
      localizations of the two types of plant LARP6 proteins and found that they
      display nonredundant characteristics. As a whole, our results support a model in
      which the acquisition by LARP4 and LARP6 of a PAM2 allowed their targeting to
      mRNA 3' UTRs and led to their neofunctionalization.

PMID- 23148095
TI  - Modestobacter roseus sp. nov., an endophytic actinomycete isolated from the
      coastal halophyte Salicornia europaea Linn., and emended description of the genus
      Modestobacter.
AB  - A novel actinomycete, designated strain KLBMP 1279(T), was isolated from surface
      sterilized roots of a coastal halophyte, Salicornia europaea Linn., collected
      from Jiangsu Province, in the east of China. The taxonomic status of this
      organism was established using a polyphasic approach. 16S rRNA gene sequence
      analysis indicated that strain KLBMP 1279(T) was closely related to Modestobacter
      marinus 42H12-1(T) (99.5% 16S rRNA gene sequence similarity), Modestobacter
      versicolor CP153-2(T) (98.4%) and Modestobacter multiseptatus AA-826(T) (97.5%).
      Chemotaxonomic characteristics were consistent with its assignment to the genus
      Modestobacter in that the isolate had meso-diaminopimelic acid as the diagnostic
      diamino acid in the cell wall, MK-9(H4) as major menaquinone and a polar lipid
      profile containing diphosphatidylglycerol, phosphatidylethanolamine,
      phosphatidylinositol, phosphatidylinositol mannosides, two unknown
      aminophospholipids and an unknown phospholipid. The predominant fatty acids were
      iso-C16:0, iso-C15:0 and C17:1omega8c. The DNA G+C content was 71.7 mol%.
      However, DNA-DNA hybridization assays as well as physiological and biochemical
      analyses differentiated strain KLBMP 1279(T) from its closest phylogenetic
      relatives. On the basis of phenotypic, chemotaxonomic and phylogenetic evidence,
      the isolate KLBMP 1279(T) represents a novel species of the genus Modestobacter,
      for which the name Modestobacter roseus sp. nov. is proposed; the type strain is
      KLBMP 1279(T) (=KCTC 19887(T)=NBRC 108673(T)=DSM 45764(T)). An emended
      description of the genus Modestobacter is also proposed.

PMID- 23148096
TI  - Description of Acidovorax wautersii sp. nov. to accommodate clinical isolates and
      an environmental isolate, most closely related to Acidovorax avenae.
AB  - Three Gram-negative strains, NF 1078(T), NF 1598 and NF 1715, were isolated from
      clinical (two) and environmental (one) samples, respectively. Sequence analysis
      of the 16S rRNA genes revealed similarity of 100% among the three strains and
      next highest similarity to the type strain of Acidovorax avenae (98.16%). The
      three strains were able to acidify lactose and rhamnose on low peptone phenol red
      agar and to alkalinize citrate on Simmons' agar and were negative for nitrate
      reduction. The DNA G+C content of strain NF 1078(T) was 67.1 mol%. The level of
      DNA-DNA relatedness between this strain and the type strains of A. avenae (ATCC
      19860(T), LMG 2117(T)) was 29%. Based on these phylogenetic, phenotypic and
      genotypic analyses, the three strains could be distinguished clearly from all
      other recognized Acidovorax species and should be classified as representatives
      of a novel species of the genus Acidovorax, for which the name Acidovorax
      wautersii sp. nov. is proposed. The type strain is NF 1078(T) (=LMG 26971(T)=CCUG
      62584(T)).

PMID- 23148097
TI  - Aspergillus waksmanii sp. nov. and Aspergillus marvanovae sp. nov., two closely
      related species in section Fumigati.
AB  - Two new and phylogenetically closely related species in Aspergillus section
      Fumigati are described and illustrated. Homothallic Aspergillus waksmanii sp.
      nov. was isolated from New Jersey soil (USA) and is represented by the ex-type
      isolate NRRL 179(T) ( = CCF 4266(T) = Thom 4138.HS2(T) = IBT 31900(T)).
      Aspergillus marvanovae sp. nov. was isolated from water with high boracic acid
      anions content in Dukovany nuclear power station (Czech Republic). The sexual
      stage of this species is unknown, but the MAT1-1 locus was successfully amplified
      suggesting that the species is probably heterothallic and teleomorphic but is
      represented by only the ex-type isolate CCM 8003(T) ( = CCF 4037(T) = NRRL
      62486(T) = IBT 31279(T) = IFM 60873(T)). Both species can be distinguished from
      all previously described species in section Fumigati based on morphology, maximum
      growth temperature, sequence data from five unlinked loci and unique secondary
      metabolites profiles.

PMID- 23148098
TI  - Flavobacterium squillarum sp. nov., isolated from a freshwater shrimp culture
      pond, and emended descriptions of Flavobacterium haoranii, Flavobacterium
      cauense, Flavobacterium terrae and Flavobacterium aquatile.
AB  - A bacterial strain, designated CMJ-5(T), was isolated from a freshwater shrimp
      culture pond in Taiwan and characterized using a polyphasic taxonomic approach.
      Cells of strain CMJ-5(T) were Gram-stain-negative, strictly aerobic, non-motile,
      yellow-pigmented rods surrounded by a thick capsule. Growth occurred at 20-35 
      degrees C (optimum, 30  degrees C), at pH 6.5-8.0 (optimum, pH 7.0) and with 0
      0.5% NaCl (optimum, 0%). Phylogenetic analyses based on 16S rRNA gene sequences
      showed that strain CMJ-5(T) belonged to the genus Flavobacterium and was related
      most closely to Flavobacterium haoranii LQY-7(T) with sequence similarity of
      94.4%. Strain CMJ-5(T) contained iso-C15:0 (37.5%), iso-C17:0 3-OH (13.4%), iso
      C15:0 3-OH (13.1%) and iso-C15:1 G (11.2%) as the predominant fatty acids. The
      major isoprenoid quinone was MK-6. The polar lipid profile consisted of
      phosphatidylethanolamine and several uncharacterized aminophospholipids and
      phospholipids. The major polyamine was homospermidine. The G+C content of the
      genomic DNA was 42.4 mol%. On the basis of phylogenetic inference and phenotypic
      data, strain CMJ-5(T) should be classified as a representative of a novel
      species, for which the name Flavobacterium squillarum sp. nov. is proposed. The
      type strain is CMJ-5(T) (=BCRC 80405(T)=LMG 26890(T)=KCTC 23915(T)). Emended
      descriptions of Flavobacterium haoranii, Flavobacterium cauense, Flavobacterium
      terrae and Flavobacterium aquatile are also proposed.

PMID- 23148099
TI  - Spirochaeta sphaeroplastigenens sp. nov., a halo-alkaliphilic, obligately
      anaerobic spirochaete isolated from soda lake Lonar.
AB  - Two helical-shaped bacteria (strains JC133(T) and JC143), which stain Gram
      negative, were isolated from an alkaline soda lake, Lonar, India. Both strains
      were obligate anaerobes, mesophilic and required halo-alkaline conditions for
      growth. Both strains were resistant to rifampicin and kanamycin, but sensitive to
      gentamicin, tetracycline, ampicillin and chloramphenicol. Both strains had
      phosphatidylglycerol (PG), diphosphotidylglycerol (DPG), glycolipid (GL) and four
      unidentified lipids (L1-4) as the major polar lipids. C18:1omega7c was the
      predominant cellular fatty acid with significant proportions of C16:0,
      C18:1omega9c, C14:0, C18:0, C16:1omega5c, C18:1omega5c and C20:1omega9c. The DNA
      G+C contents of strain JC131(T) and JC143 were 58.2 and 58.5 mol%, respectively,
      and the two strains showed DNA reassociation >85% (based on DNA-DNA
      hybridization). Based on the 16S rRNA gene sequence analysis, both strains were
      identified as belonging to the genus Spirochaeta with Spirochaeta alkalica Z
      7491(T) (99.6% sequence similarity), Spirochaeta americana ASpG1(T) (99 %) and
      other members of the genus Spirochaeta (<93%) as their closest phylogenetic
      neighbours. However, strain JC133(T) and JC143 displayed less than 53.5 % binding
      (based on DNA-DNA hybridization) with S. alkalica Z-7491(T) and S. americana
      ASpG1(T). On the basis of physiological, biochemical, chemotaxonomic and
      molecular properties, strains JC133(T) and JC143 can be differentiated from other
      members of the genus Spirochaeta and represent a novel species of the genus
      Spirochaeta, for which the name Spirochaeta sphaeroplastigenens sp. nov. is
      proposed. The type strain is JC133(T) ( = KCTC 15220(T) = NBRC 109056(T)).

PMID- 23148100
TI  - Sphingobacterium caeni sp. nov., isolated from activated sludge.
AB  - The taxonomic status of a bacterium, strain DC-8(T), isolated from activated
      sludge, was determined using a polyphasic taxonomic approach. The cells of strain
      DC-8(T) were Gram-negative, non-motile, non-spore-forming and rod-shaped. The
      isolate grew at temperature range of 10-40  degrees C (optimum 30-35  degrees C),
      pH range of 5.0-10.0 (optimum 6.5-8.0) and NaCl concentrations of 0-5% (optimum 0
      1%). The predominant menaquinone of strain DC-8(T) was MK-7 and major fatty acids
      were summed feature 3 (C16:1omega6c and/or C16:1omega7c; 39.7%), iso-C15:0
      (33.7%) and C16:0 (5.2%). The DNA G+C content was 39.8 mol%. Phylogenetic
      analysis based on 16S rRNA gene sequence comparison revealed that strain DC-8(T)
      was a member of the genus Sphingobacterium. Strain DC-8(T) shared the highest
      similarity with Sphingobacterium siyangense SY1(T) (98.4%), Sphingobacterium
      multivorum IAM 14316(T) (98.3%), Sphingobacterium canadense CR11(T) (98.0%) and
      Sphingobacterium detergens 6.2S(T) (97.9%) and shared less than 97% similarity
      with other members of the genus Sphingobacterium. DNA-DNA hybridization
      experiments showed that the DNA-DNA relatedness values between strain DC-8(T) and
      its closest phylogenetic neighbours were below 70%. Based on the phylogenetic
      analysis, DNA-DNA hybridization, whole-cell fatty acid composition as well as
      biochemical characteristics, strain DC-8(T) was clearly distinguished from all
      recognized species of the genus Sphingobacterium and should be classified as a
      representative of a novel species of the genus Sphingobacterium, for which the
      name Sphingobacterium caeni sp. nov. is proposed. The type strain is DC-8(T)
      (=CCTCC AB 2012020(T)=KACC 16850(T)).

PMID- 23148101
TI  - Paramoritella sediminis sp. nov., isolated from marine sediment, and emended
      descriptions of the genus Paramoritella Hosoya et al. 2009 and Paramoritella
      alkaliphila.
AB  - A Gram-negative, facultatively anaerobic, rod-shaped (2.04-1.27 * 0.95-1.25 um)
      and motile marine bacterium, designated MEBiC06500(T) was isolated from sediment
      collected at Daebu Island in the Yellow Sea (37 degrees  20' N 126 degrees  41'
      E), Korea. 16S rRNA gene sequence analysis revealed that strain MEBiC06500(T)
      showed high similarity with Paramoritella alkaliphila A3F-7(T) (96.5%). Growth
      was observed at 10.5-30.2  degrees C (optimum 23.5  degrees C), at pH 6.0-9.5
      (optimum 8.0) and with 0-5% (optimum 1.5%) NaCl. The predominant cellular fatty
      acids were C14:0, C16:0, C18:1omega7c and summed feature 3 (iso-C15:0 2-OH and/or
      C16:1omega7c). The DNA G+C content was 56.0 mol%. The respiratory quinone is Q-8.
      Phosphatidylethanolamine, phosphatidylglycerol, diphosphatidylglycerol, four
      unidentified lipids, one unidentified phospholipid and three unidentified
      aminolipids were detected as major polar lipids. On the basis of this polyphasic
      taxonomic data, strain MEBiC06500(T) should be classified as a representative of
      a novel species in the genus Paramoritella, and the proposed name is
      Paramoritella sediminis sp. nov. The type strain is MEBiC06500(T) (=KCCM
      42977(T)=JCM 18292(T)). Emended descriptions of the genus Paramoritella Hosoya et
      al. 2009 and Paramoritella alkaliphila are also given.

PMID- 23148102
TI  - Thalassolituus marinus sp. nov., a hydrocarbon-utilizing marine bacterium.
AB  - Gram-negative strains, motile by a single polar flagellum, non-pigmented and with
      a curved rod-shaped morphology, designated IMCC1826(T) and IMCC1883, were
      isolated from a surface seawater sample from the Yellow Sea. The two strains
      shared 99.9% 16S rRNA gene sequence similarity and showed 92% DNA-DNA
      relatedness, suggesting that they belonged to the same genomic species.
      Phylogenetic analysis based on 16S rRNA gene sequences showed that the two
      isolates were related most closely to the type strain of Thalassolituus
      oleivorans with a sequence similarity of 96.4% and formed a robust phyletic
      lineage with T. oleivorans. DNA-DNA relatedness between the two strains and T.
      oleivorans DSM 14913(T) was 8.7-11.6%. A putative alkane hydroxylase (alkB) gene
      was detected in strain IMCC1826(T) by PCR, but the amino acid sequence of the
      gene was distantly related to that of the AlkB homologue of T. oleivorans DSM
      14913(T). As expected from the presence of the alkB gene, the new strains
      utilized n-tetradecane and n-hexadecane as a carbon source. The DNA G+C content
      was 54.6-56.0 mol% and the main isoprenoid quinone detected was Q-9. Polar lipids
      of strain IMCC1826(T) included diphosphatidylglycerol, phosphatidylglycerol,
      phosphatidylethanolamine and amino-group-containing lipids. On the basis of
      taxonomic data obtained in this study, strains IMCC1826(T) and IMCC1883 represent
      a novel species of the genus Thalassolituus, for which the name Thalassolituus
      marinus sp. nov. is proposed, with IMCC1826(T) (=KCTC 23084(T)=NBRC 107590(T)) as
      the type strain.

PMID- 23148103
TI  - Rubrivirga marina gen. nov., sp. nov., a member of the family Rhodothermaceae
      isolated from deep seawater.
AB  - Two aerobic, Gram-stain-negative, pale-red-pigmented and rod-shaped bacterial
      strains, designated SAORIC-26 and SAORIC-28(T), were isolated from seawater (3000
      m depth) from the Pacific Ocean. Phylogenetic analysis based on their 16S rRNA
      gene sequences revealed that the novel isolates could be affiliated with the
      family Rhodothermaceae of the class Cytophagia. Strains SAORIC-26 and SAORIC
      28(T) shared 99.7% pairwise sequence similarity with each other and showed less
      than 92.6% similarity with other cultivated members of the class Cytophagia. The
      strains were found to be non-motile, oxidase-positive, catalase-negative and able
      to hydrolyse gelatin and aesculin. The DNA G+C contents were determined to be
      64.8-65.8 mol% and MK-7 was the predominant menaquinone. Summed feature 9 (iso
      C17:1omega9c and/or C16:0 10-methyl), summed feature 3 (C16:1omega6c and/or
      C16:1omega7c) and iso-C15:0 were found to be the major cellular fatty acids. On
      the basis of this taxonomic study using a polyphasic approach, it was concluded
      that strains SAORIC-26 and SAORIC-28(T) represent a novel species of a new genus
      in the family Rhodothermaceae, for which the name Rubrivirga marina gen. nov.,
      sp. nov. is proposed. The type strain of the type species of is SAORIC-28(T)
      (=KCTC 23867(T)=NBRC 108816(T)). An additional strain of the species is SAORIC
      26.

PMID- 23148104
TI  - Methylophaga nitratireducenticrescens sp. nov. and Methylophaga frappieri sp.
      nov., isolated from the biofilm of the methanol-fed denitrification system
      treating the seawater at the Montreal Biodome.
AB  - Two bacterial strains, designated JAM1(T) and JAM7(T), were isolated from a
      methanol-fed denitrification system treating seawater at the Montreal Biodome,
      Canada. They were affiliated within the genus Methylophaga of the
      Gammaproteobacteria by analysis of the 16S rRNA gene sequences. Strain JAM1(T)
      had the capacity to grow under denitrifying conditions by reducing nitrate into
      nitrite which is unique among the species of the genus Methylophaga. Major fatty
      acids were C16:1omega7c or omega6c, C16:0 and C18:1omega7c or omega6c. The major
      ubiquinone was Q8. Both strains required vitamin B12 and Na(+) ions for growth.
      The genomes of strains JAM1(T) and JAM7(T) have been completely sequenced and
      showed a DNA G+C content of 44.7 mol% and 47.8 mol%, respectively. Growth
      occurred at pH 6-11 and at 0.5-8% NaCl. Both genomes contained predicted ORFs
      encoding the key enzymes of the ribulose monophosphate pathway. Also, operons
      encoding two nitrate reductases (Nar), two nitric oxide reductases (Nor), one
      nitrous oxide reductase (Nos) and one truncated nitrite reductase (NirK) were
      clustered in a 67 kb chromosomal region in strain JAM1(T). No such operons were
      found in strain JAM7(T). These results supported the affiliation of the two
      strains as novel species within the genus Methylophaga. The names Methylophaga
      nitratireducenticrescens sp. nov. for type strain JAM1(T) (=DSM 25689(T)=ATCC BAA
      2433(T)) and Methylophaga frappieri sp. nov. for type strain JAM7(T) (=DSM
      25690(T)=ATCC BAA-2434(T)) are proposed.

PMID- 23148106
TI  - Body mass index in relation to oesophageal and oesophagogastric junction
      adenocarcinomas: a pooled analysis from the International BEACON Consortium.
AB  - BACKGROUND: Previous studies suggest an association between obesity and
      oesophageal (OA) and oesophagogastric junction adenocarcinomas (OGJA). However,
      these studies have been limited in their ability to assess whether the effects of
      obesity vary by gender or by the presence of gastro-oesophageal reflux (GERD)
      symptoms. METHODS: Individual participant data from 12 epidemiological studies (8
      North American, 3 European and 1 Australian) comprising 1997 OA cases, 1900 OGJA
      cases and 11 159 control subjects were pooled. Logistic regression was used to
      estimate study-specific odds ratios (ORs) and 95% confidence intervals (CIs) for
      the association between body mass index (BMI, kg/m(2)) and the risk of OA and
      OGJA. Random-effects meta-analysis was used to combine these ORs. We also
      investigated effect modification and synergistic interaction of BMI with GERD
      symptoms and gender. RESULTS: The association of OA and OGJA increased directly
      with increasing BMI (P for trend <0.001). Compared with individuals with a BMI
      <25, BMI >=40 was associated with both OA (OR 4.76, 95% CI 2.96-7.66) and OGJA
      (OR 3.07, 95% CI 1.89-4.99). These associations were similar when stratified by
      gender and GERD symptoms. There was evidence for synergistic interaction between
      BMI and GERD symptoms in relation to OA/OGJA risk. CONCLUSIONS: These data
      indicate that BMI is directly associated with OA and OGJA risk in both men and
      women and in those with and without GERD symptoms. Disentangling the relationship
      between BMI and GERD will be important for understanding preventive efforts for
      OA and OGJA.

PMID- 23148108
TI  - Demographic and health surveys: a profile.
AB  - Demographic and Health Surveys (DHS) are comparable nationally representative
      household surveys that have been conducted in more than 85 countries worldwide
      since 1984. The DHS were initially designed to expand on demographic, fertility
      and family planning data collected in the World Fertility Surveys and
      Contraceptive Prevalence Surveys, and continue to provide an important resource
      for the monitoring of vital statistics and population health indicators in low-
      and middle-income countries. The DHS collect a wide range of objective and self
      reported data with a strong focus on indicators of fertility, reproductive
      health, maternal and child health, mortality, nutrition and self-reported health
      behaviours among adults. Key advantages of the DHS include high response rates,
      national coverage, high quality interviewer training, standardized data
      collection procedures across countries and consistent content over time, allowing
      comparability across populations cross-sectionally and over time. Data from DHS
      facilitate epidemiological research focused on monitoring of prevalence, trends
      and inequalities. A variety of robust observational data analysis methods have
      been used, including cross-sectional designs, repeated cross-sectional designs,
      spatial and multilevel analyses, intra-household designs and cross-comparative
      analyses. In this profile, we present an overview of the DHS along with an
      introduction to the potential scope for these data in contributing to the field
      of micro- and macro-epidemiology. DHS datasets are available for researchers
      through MEASURE DHS at www.measuredhs.com.

PMID- 23148107
TI  - Correction for population stratification in random forest analysis.
AB  - BACKGROUND: Population structure (PS), including population stratification and
      admixture, is a significant confounder in genome-wide association studies (GWAS),
      as it may produce spurious associations. Random forest (RF) has been increasingly
      applied in GWAS data analysis because of its advantage in analysing high
      dimensional genetic data. RF creates importance measures for single nucleotide
      polymorphisms (SNPs), which are helpful for feature selections. However, if PS is
      not appropriately corrected, RF tends to give high importance to disease
      unrelated SNPs with different frequencies of allele or genotype among
      subpopulations, leading to inaccurate results. METHODS: In this study, the
      authors propose to correct for the confounding effect of PS by including the
      information of PS in RF analysis. The correction procedure starts by extracting
      the information of PS using EIGENSTRAT or multi-dimensional scaling clustering
      procedure from a large number of structure inference SNPs. Phenotype and
      genotypes adjusted by the information of PS are then used as the outcome and
      predictors in RF analysis. RESULTS: Extensive simulations indicate that the
      importance measure of the causal SNP is increased following the PS correction. By
      analysing a real dataset, the proposed correction removes the spurious
      association between the lactase gene and height. CONCLUSION: The authors propose
      a simple method to correct for PS in RF analysis on GWAS data. Further studies in
      real GWAS datasets are required to validate the robustness of the proposed
      approach.

PMID- 23148109
TI  - Effects of the UK Biobank collection protocol on potential biomarkers in saliva.
AB  - BACKGROUND: The UK Biobank (UKB) is a national epidemiological study of the
      health of 500 000 people, aged 40-69 years, who completed health-related tests
      and a questionnaire and gave samples of blood and urine. Salivas collected from
      120 000 of these subjects were transported at 4 degrees C and were placed in
      ultra-low temperature archives at up to 24 h after collection. The present study
      assessed how changes in saliva composition under UKB conditions influence a range
      of potential biomarkers resulting from holding saliva at 4 degrees C for 24 h.
      METHODS: Unstimulated whole-mouth saliva samples were collected from 23
      volunteers aged 45-69 years. Salivas were split into aliquots some of which were
      immediately frozen at -80 degrees C, whereas others were stored at 4 degrees C
      for 24 h and then frozen at -80 degrees C, mimicking the UKB protocol. RESULTS:
      Assessment of mRNA by real-time polymerase chain reaction revealed no difference
      between samples that were analysed after the UKB protocol and those that were
      immediately preserved. Immunochemical analysis showed some loss of beta-Actin
      under UKB conditions, whereas other salivary proteins including cytokines and C
      reactive protein appeared to be unaffected. Cortisol and showed no reduction by
      UKB conditions, but salivary nitrite was reduced by 30%. The oral microbiome, as
      revealed by sequencing 16S rRNA genes, showed variations between subjects, but
      paired samples within subjects were very similar. CONCLUSIONS: Our results
      suggest that many salivary components remain little affected under UKB collection
      and handling protocols, suggesting that the resource of 120 000 samples held in
      storage will be useful for phenotyping subjects and revealing potential
      prognostic disease biomarkers.

PMID- 23148110
TI  - Assessment of knowledge and attitudes regarding automated external defibrillators
      and cardiopulmonary resuscitation among American University students.
AB  - AIM: We sought to quantify knowledge and attitudes regarding automated external
      defibrillators (AEDs) and cardiopulmonary resuscitation (CPR) among university
      students. We also aimed to determine awareness of the location of an actual AED
      on campus. METHODS: We performed an online survey of undergraduate and graduate
      students at a mid-sized, private university that has 37 AEDs located throughout
      its two campuses. RESULTS: 267 students responded to the survey. Almost all
      respondents could identify CPR (98.5%) and an AED (88.4%) from images, but only
      46.1% and 18.4%, respectively, could indicate the basic mechanism of CPR and
      AEDs. About a quarter (28.1%) of respondents were comfortable using an AED
      without assistance, compared with 65.5% when offered assistance. Of those who did
      not feel comfortable, 87.7% indicated that they were 'afraid of doing something
      wrong.' One out of 6 (17.6%) respondents knew that a student centre had an AED,
      and only 2% could recall its precise location within the building. Most (66.3%)
      respondents indicated they would look for an AED near fire extinguishers,
      followed by the entrance of a building (19.6%). CONCLUSIONS: This study found
      that most students at an American university can identify CPR and AEDs, but do
      not understand their basic mechanisms of action or are willing to perform CPR or
      use AEDs unassisted. Recent CPR/AED training and 9-1-1 assistance increases
      comfort. The most common fear reported was incorrect CPR or AED use. Almost all
      students could not recall where an AED was located in a student centre.

PMID- 23148111
TI  - A child with severe stridor.

PMID- 23148112
TI  - Stress distribution and displacement by different bone-borne palatal expanders
      with micro-implants: a three-dimensional finite-element analysis.
AB  - The aim of this study was to analyze stress distribution and displacement of the
      maxilla and teeth according to different designs of bone-borne palatal expanders
      using micro-implants. A three-dimensional (3D) finite-element (FE) model of the
      craniofacial bones and maxillary teeth was obtained. Four designs of rapid
      maxillary expanders: one with micro-implants placed lateral to mid-palatal suture
      (type 1), the second at the palatal slope (type 2), the third as in type 1 with
      additional conventional Hyrax arms (type 3), and the fourth surgically assisted
      tooth-borne expander (type 4) were added to the FE models. Expanders were
      activated transversely for 0.25mm. Geometric nonlinear theory was applied to
      evaluate Von-Mises Stress distribution and displacement. All types exhibited
      downward displacement and demonstrated more horizontal movement in the posterior
      area. Type 3 showed the most transverse displacement. The rotational movement of
      dentoalveolar unit was larger in types 1 and 3, whereas it was relatively
      parallel in types 2 and 4. The stresses were concentrated around the micro
      implants in types 1 and 3 only. Type 2 had the least stress concentrations around
      the anchorage and showed alveolar expansion without buccal inclination. It is
      recommended to apply temporary anchorage devices to the palatal slopes to support
      expanders for efficient treatment of maxillary transverse deficiency.

PMID- 23148113
TI  - The diagnostic potential of static body-sway recording in orthodontics: a
      systematic review.
AB  - Conflicting data have been reported in dentistry regarding the diagnostic
      potential of monitoring body sway while in a static standing bipedalic position.
      This systematic review reappraises previously reported effects of mandibular
      position, asymmetric occlusion, and temporomandibular disorders (TMDs) on body
      sway to determine whether there is sufficient evidence for such correlations and
      to define the potential diagnostic applications in orthodontics. A literature
      survey was performed using the Medline, LILACS, and SciELO databases, and the
      Cochrane Library, covering the period from January 1980 to December 2011. Twelve
      articles qualified for the final analysis. All of these studies investigated the
      effects of mandibular position, two focussed also on asymmetrical occlusion, and
      three on TMDs. Only two studies were judged to be of medium or medium/high
      quality, with all of the rest classified as low-quality design; no study included
      follow-up. According to the conclusions of these reports, four studies saw
      significant correlations between body sway and mandibular position or TMDs. After
      a reappraisal of the full data set, generally no clinically relevant correlations
      were uncovered in the comparisons. While more investigations with improved levels
      of scientific evidence are needed, according to current evidence, the static
      monitoring of body sway as a diagnostic aid in orthodontics may not be indicated.

PMID- 23148114
TI  - Influence of sucking habits and breathing pattern on palatal constriction in
      unilateral posterior crossbite--a controlled study.
AB  - The aim of this study was to evaluate the influence of prolonged sucking habits
      and mouth breathing on palatal vault morphology in a group of subjects with
      unilateral functional crossbite [crossbite (CB) group] compared with a group of
      subjects with normal occlusion [non-crossbite (NCB) group]. A sample of 80
      Caucasian subjects (51 CB and 29 NCB; aged 5.3 +/- 0.8 years) in the deciduous
      dentition was selected. A questionnaire regarding the subject's sucking habits
      was answered by the parents. Any sucking habit that lasted more than 24 months
      was considered as a prolonged sucking habit. The breathing pattern was assessed
      by an experienced otorinolarygologist and was classified either mainly nose or
      mouth breathing. Intercanine and intermolar distances and palatal surface area
      and volume were recorded three dimensionally on study casts. Univariate and
      multivariate analyses were employed. Posterior CB was negatively correlated with
      all the dental and palatal parameters (P < 0.01) with the exception of the
      palatal surface area that did not reach the statistical significance. Only
      prolonged sucking habits (but not mouth breathing) was a significant risk
      indicator for unilateral functional CB (P < 0.001). However, the prolonged
      sucking habits were not significantly correlated with any of the investigated
      parameter, and mouth breathing was negatively correlated with the intermolar
      distance only. Therefore, maxillary constriction in unilateral functional CB
      might not be influenced by the presence or absence of prolonged sucking habits or
      mouth breathing.

PMID- 23148115
TI  - Molecular changes in detrained & retrained adult jaw muscle.
AB  - A hypofunctional masticatory system was developed in 21-day-old male rats by
      feeding them a soft diet for 27 weeks. Retraining of a parallel group for 6 weeks
      was achieved by switching back to a hard diet after 21 weeks. A control group was
      fed a hard diet for 27 weeks. At the end of the experimental period, the
      expression levels of the myosin heavy chain isoform genes MYH 1 and 2 (fast), 3
      (embryonic) and 7 (slow) in the deep masseter were compared using qRT-PCR
      analysis. The gene expressions of MYH 3 and MYH 7 were significantly higher in
      the rehabilitation group compared with the normal and hypofunctional group, but
      no significant differences were found in regards to the gene expression of MYH 1
      and 2. Retraining made it possible for the slow (MYH 7) isoform levels to adapt
      to the increased mechanical load. The increased level of embryonic (MYH 3)
      isoform could be due to the need of creation of new MYH isoforms. 

PMID- 23148116
TI  - The impact of multivessel disease with and without a co-existing chronic total
      occlusion on short- and long-term mortality in ST-elevation myocardial infarction
      patients with and without cardiogenic shock.
AB  - AIMS: To evaluate the impact of multivessel disease (MVD) with and without a
      chronic total occlusion (CTO) on early and late mortality in ST-elevation
      myocardial infarction (STEMI) patients with and without cardiogenic shock (CS).
      METHODS AND RESULTS: A total of 5018 STEMI patients were treated with primary
      percutaneous coronary intervention and stratified according to the presence of CS
      and the extent of coronary artery disease into single vessel disease (SVD), MVD
      without a CTO, and MVD with a CTO. We performed a landmark mortality analysis up
      to 5-year follow-up with a landmark set at 30 days. In patients without CS (n =
      4409), only MVD with a CTO was an independent predictor for 30-day [hazard ratio
      (HR) 2.8, P < 0.01] and 5-year mortality (HR 1.7, P < 0.01), whereas MVD without
      a CTO was not associated with increased mortality. In CS patients (n = 609), MVD
      with and without a CTO were independent predictors for 30-day mortality (HR 2.2,
      P < 0.01 and HR 1.8, P < 0.01). In 30-day CS survivors, only MVD with a CTO was
      associated with a trend towards increased mortality (HR 1.7, P = 0.06).
      CONCLUSION: In non-CS STEMI patients with MVD, the presence of a co-existing CTO
      in a non-infarct-related artery drives early and late mortality. In patients with
      CS, MVD with and without a CTO were predictors for short-term mortality.

PMID- 23148117
TI  - Cost-of-illness study of patients subjected to cardiac rhythm management devices
      implantation: results from a single tertiary centre.
AB  - AIMS: The aim of the present study is to estimate the procedure (implantation)
      cost, the total hospitalization cost and annual follow-up cost, in patients
      subjected to pacemaker (PM) and implantable cardioverter-defibrillator (ICD)
      implantation. METHODS AND RESULTS: A single-center, prospective, cost-of-illness
      study was conducted between August 2008 and July 2009. In total, 464 consecutive
      patients were recruited (370 were subjected to PM implantation and 94 to ICD
      implantation). Resource data were assessed at patients' enrolment in the study
      and at 6th and 12th months of patients' follow-up. Then, the procedure cost, the
      total hospitalization cost as well as the annual patients' follow up costs were
      calculated using a bottom-up approach. The mean (95% confidence interval)
      procedure cost of PM and ICD implantation (including the costs of devices,
      electrodes, other supplies, and personnel's time) was calculated to be ?1803
      (?1758-?1858) and ?13,521 (?13,153-?13,892), respectively. The mean total
      hospitalization cost (including procedure cost, hospitalization cost, cost of
      laboratory and imaging diagnostic examinations and the indirect cost attributed
      to productivity lost due to patient's hospitalization) was ?3926 (?3711-?4167)
      for PM and ?17,764 (?16,852-?18,692) for ICD. The mean annual cost (direct and
      indirect) was ?1816 (?1433-?2421) for PM and ?2819 (?2115-?3703) for ICD. No
      difference was detected in the annual cost between patients with initial
      implantation and replacement. CONCLUSION: These data revealed that although these
      devices are associated with a relatively high upfront cost, the annual societal
      cost following the implantation is low. Therefore, implantation of such devices
      should be encouraged since these devices reduce the morbidity and mortality
      without a high economic burden to society.

PMID- 23148118
TI  - Areas with complex fractionated atrial electrograms recorded after pulmonary vein
      isolation represent normal voltage and conduction velocity in sinus rhythm.
AB  - AIMS: Although complex fractionated atrial electrograms (CFAEs) are purported to
      represent critical sites for atrial fibrillation (AF) perpetuation, the mechanism
      and the significance of CFAE in the genesis of AF remain poorly understood. This
      study evaluated the relationship between CFAE and areas of abnormal atrial tissue
      defined by low-voltage electrograms (LVE) and signal average of the P-wave
      (SAPW). METHODS AND RESULTS: Complex fractionated atrial electrogram maps were
      obtained after pulmonary vein isolation in 15 patients with persistent AF.
      Patients were then cardioverted and voltage/activation maps were acquired in
      normal sinus rhythm (NSR). Total left atrium (LA), CFAE and LVE areas were
      measured as % of total LA area (mean +/- SD). Conduction velocities of normal,
      LVE and CFAE areas were also measured during NSR. Patients underwent signal
      averaged ECG of the P-wave in NSR within 24 h of the procedure. Complex
      fractionated atrial electrograms areas accounted for 33 +/- 24% of total LA. In
      NSR, only 12 +/- 10% of LA area had LVE. There was no anatomic correlation
      between CFAE sites and LVE; the area of overlap between CFAE and LVE was only 1.6
      +/- 1.5%. Conduction velocity was faster in CFAE areas (2.3 +/- 1.4 m/s) than in
      normal voltage areas (1.3 +/- 0.3 m/s), and LVE areas (1.1 +/- 0.7 m/s, P =
      0.06). A positive correlation was only found between LVE areas and SAPW duration
      (r = 0.7, P = 0.04). CONCLUSION: Areas of CFAEs correspond to areas of normal
      atrial voltage and normal conduction velocity during NSR. Complex fractionated
      atrial electrogram probably represents the response of normal healthy atrial
      tissue to rapid pulmonary vein activation.

PMID- 23148119
TI  - Diagnostic yield of FDG positron-emission tomography/computed tomography in
      patients with CEID infection: a pilot study.
AB  - AIMS: Whole body imaging with (18)F-fluorodeoxyglucose positron-emission
      tomography/computed tomography (FDG PET/CT) has proven useful in various
      infectious diseases. The purpose of this pilot study was to assess the diagnostic
      yield of FDG PET/CT in patients with cardiac implantable electronic device (CIED)
      infection. METHODS AND RESULTS: A total of 21 patients with CIED infection were
      prospectively included. Diagnosis of CIED infection was made in accordance with
      current criteria. It was classified in three categories, i.e. superficial skin
      infection, pocket site infection, or cardiac device-related infective
      endocarditis (CDRIE). All patients underwent FDG PET/CT. Scans were interpreted
      blindly, i.e. without prior knowledge of diagnosis, by experienced nuclear
      medicine physicians. The accuracy of FDG PET/CT was assessed for each diagnostic
      category. Findings demonstrated superficial skin infection in 1 patient, pocket
      site infection in 15, and CDRIE in 13 (definite: 7; possible: 6). In patients
      with pocket site infection, the sensitivity and specificity of FDG PET/CT were
      86.7% [59.5-98.3, 95% confidence interval (CI)] and 100% [42.1-100, 95% CI]. The
      only patient with superficial skin infection was accurately identified by FDG
      PET/CT. The sensitivity and specificity of FDG PET/CT in patients with CDRIE were
      30.8% [9.1-61.4, 95% CI] and 62.5% [24.5-91.5, 95% CI]. Most false-negative
      results occurred in patients who had undergone previous antimicrobial treatment.
      CONCLUSION: This study indicates that FDG PET/CT is highly accurate for the
      diagnosis of skin and pocket CIED infection but low for infective endocarditis.
      This suggests that the reliability of FDG PET/CT findings in management decision
      making varies according to the type of CIED infection.

PMID- 23148120
TI  - Incidence and prognostic significance of spontaneous and inducible antidromic
      tachycardia.
AB  - AIMS: Orthodromic atrioventricular reentrant tachycardia (ORT) is the most common
      arrhythmia at electrophysiological study (EPS) in patients with pre-excitation.
      The purpose of the study was to determine the clinical significance and the
      electrophysiological characteristics of patients with inducible antidromic
      tachycardia (ADT). METHODS AND RESULTS: Electrophysiological study was performed
      in 807 patients with a pre-excitation syndrome in control state and after
      isoproterenol. Antidromic tachycardia was induced in 63 patients (8%). Clinical
      and electrophysiological data were compared with those of 744 patients without
      ADT. Patients with and without ADT were similar in term of age (33 +/- 18 vs. 34
      +/- 17), male gender (68 vs. 61%), clinical presentation with spontaneous
      atrioventricular reentrant tachycardia (AVRT) (35 vs. 42%), atrial fibrillation
      (AF) (3 vs. 3%), syncope (16 vs. 12%). In patients with induced ADT, asymptomatic
      patients were less frequent (24 vs. 37%; <0.04), spontaneous ADT and spontaneous
      malignant form more frequent (8 vs. 0.5%; <0.001) (16 vs. 6%; <0.002). Left
      lateral accessory pathway (AP) location was more frequent (51 vs. 36%; P <
      0.022), septal location less frequent (40 vs. 56%; P < 0.01). And 1/1 conduction
      through AP was more rapid. Orthodromic AVRT induction was as frequent (55.5 vs.
      55%), but AF induction (41 vs. 24%; P < 0.002) and electrophysiological malignant
      form were more frequent (22 vs. 12%; P < 0.02). The follow-up was similar; four
      deaths and three spontaneous malignant forms occurred in patients without ADT.
      When population was divided based on age (<20/>=20 years), the older group was
      less likely to have criteria for malignant form. CONCLUSION: Antidromic
      tachycardia induction is rare in pre-excitation syndrome and generally is
      associated with spontaneous or electrophysiological malignant form, but clinical
      outcome does not differ.

PMID- 23148121
TI  - Assessing primary care in Austria: room for improvement.
AB  - BACKGROUND: There is emerging evidence that strong primary care achieves better
      health at lower costs. Although primary care can be measured, in many countries,
      including Austria, there is little understanding of primary care development.
      OBJECTIVE: Assessing the primary care development in Austria. METHODS: A primary
      care assessment tool developed by Barbara Starfield in 1998 was implemented in
      Austria. This tool defines 15 primary care characteristics and distinguishes
      between system and practice characteristics. Each characteristic was evaluated by
      six Austrian primary care experts and rated as 2 (high), 1 (intermediate) or 0
      (low) points, respectively, to their primary care strength (maximum score: n =
      30). RESULTS: Austria received 7 out of 30 points; no characteristic was rated as
      '2' but 8 were rated as '0'. Compared with the 13 previously assessed countries,
      Austria ranks 10th of 14 countries and is classified as a 'low primary care'
      country. CONCLUSION: This study provides the first evidence concerning primary
      care in Austria, benchmarking it as weak and in need of development. The
      practicable application of an existing assessment tool can be encouraging for
      other countries to generate evidence about their primary care system as well.

PMID- 23148122
TI  - Letter to the editor regarding the report of Duboc et al: Connecting dysbiosis,
      bile-acid dysmetabolism and gut inflammation in inflammatory bowel disease.

PMID- 23148126
TI  - Z-Group ketone chain transfer agents for RAFT polymer nanoparticle modification
      via hydrazone conjugation.
AB  - A ketal-containing trithiocarbonyl compound has been synthesized and
      characterized as a chain transfer agent (CTA) in Reversible Addition
      Fragmentation Transfer (RAFT) polymerization. The ketal functionality does not
      interfere with RAFT polymerization of acrylate monomers, which proceeds as
      previously reported to yield macro-CTA polymers and block co-polymers. Post
      polymerization ketal cleavage revealed ketone functionality at the polar terminus
      of an amphiphilic block co-polymer. Hydrazone-formation was facile in both
      organic solution as well as in aqueous buffer where polymer nanoparticle
      assemblies were formed, indicating a conjugation/end-functionalization yield of
      40-50%. Conjugation was verified with fluorescein, biotin and Gd-DOTA
      derivatives, and though the trithiocarbonate linkage is hydrolytically labile, we
      observed stable conjugation for several days at pH 7.4. and 37 degrees C. As
      expected, streptavidin binding to biotinylated polymer micelles was observed, and
      size-change based relaxivity increases were observed when Gd-DOTA hydrazide was
      conjugated to polymer micelles. Cell-uptake of fluorescently labeled polymer
      micelles was also readily tracked by FACS and fluorescence microscopy. These
      polymer derivatives demonstrate a range of potential theranostic/biotechnological
      applications for this conveniently accessible keto-CTA, which include ligand
      based nanoparticle targeting and fluorescent/MR nanoparticle contrast agents.

PMID- 23148127
TI  - How Bacteria Adhere to Brushy PEG Surfaces: Clinging to Flaws and Compressing the
      Brush.
AB  - This study examined the compression of solvated polymer brushes on bioengineered
      surfaces during the initial stages of Staphylococcus Aureus (S. aureus) adhesion
      from gentle flow. A series of PEG [poly(ethylene glycol)] brushes, 7 to 17 nm in
      height and completely non-adhesive to proteins and bacteria, were modified by the
      incorporation of sparse isolated ~10 nm cationic polymer "patches" at their
      bases. These nanoscale regions, which lacked PEG tethers, were electrostatically
      attractive towards negative bacteria or proteins. S. aureus drawn to the
      interface by multiple adhesive patches compressed the PEG brush in the remaining
      contact region. The observed onset of bacterial or fibrinogen capture with
      increases in patch content was compared with calculations. Balancing the
      attraction energy (proportional to the number of patches engaging a bacterium
      during capture) against steric forces (calculated using the Alexander-DeGennes
      treatment) provided perspective on the brush compression. The results were
      consistent with a bacteria-surface gap on the order of the Debye length in these
      studies. In this limit of strong brush compression, structural features (height,
      persistence length) of the brush were unimportant so that osmotic pressure
      dominated the steric repulsion. Thus, the dominant factor for bacterial repulsion
      was the mass of PEG in the brush. This result explains empirical reports in the
      literature that identify the total PEG content of a brush as a criteria for
      prevention of bioadhesion, independent of tether length and spacing, within a
      reasonable range for those parameters. Bacterial capture was also compared to
      that of protein capture. It was found, surprisingly, that the patchy brushes were
      more protein-than bacteria-resistant. S. aureus adhesion driven by patches within
      otherwise protein-resistant PEG brushes was explained by the bacteria's greater
      tendency to compress large areas of brush to interact with many patches. By
      contrast, proteins are thought to penetrate the brush at a few sites of PEO-free
      patches. The finding provides a mechanism for the literature reports that in
      vitro protein resistance is a poor predictor of in-vitro implant failure related
      to cell-surface adhesion.

PMID- 23148128
TI  - The cochlea as a smart structure.
AB  - The cochlea is part of the inner ear and its mechanical response provides us with
      many aspects of our amazingly sensitive and selective hearing. The human cochlea
      is a coiled tube, with two main fluid chambers running along its length,
      separated by a 35 mm-long flexible partition that has its own internal dynamics.
      A dispersive wave can propagate along the cochlea due to the interaction between
      the inertia of the fluid and the dynamics of the partition. This partition
      includes about 12 000 outer hair cells, which have different structures, on a
      micrometre and a nanometre scale, and act both as motional sensors and as
      motional actuators. The local feedback action of all these cells amplifies the
      motion inside the inner ear by more than 40 dB at low sound pressure levels. The
      feedback loops become saturated at higher sound pressure levels, however, so that
      the feedback gain is reduced, leading to a compression of the dynamic range in
      the cochlear amplifier. This helps the sensory cells, with a dynamic range of
      only about 30 dB, to respond to sounds with a dynamic range of more than 120 dB.
      The active and nonlinear nature of the dynamics within the cochlea give rise to a
      number of other phenomena, such as otoacoustic emissions, which can be used as a
      diagnostic test for hearing problems in newborn children, for example. In this
      paper we view the mechanical action of the cochlea as a smart structure. In
      particular a simplified wave model of the cochlear dynamics is reviewed that
      represents its essential features. This can be used to predict the motion along
      the cochlea when the cochlea is passive, at high levels, and also the effect of
      the cochlear amplifier, at low levels.

PMID- 23148129
TI  - Temporal Differences in Remarriage Timing: Comparing Divorce and Widowhood.
AB  - One gap in the remarriage literature to date concerns the timing of remarriage
      among different groups. This paper begins to fill this gap by examining the tempo
      of remarriage among individuals whose first marriages ended in divorce and
      individuals whose first marriages ended in spousal death. Drawing on event
      history models, the results suggest that divorced individuals remarry quicker
      than individuals whose first marriage ended in spousal death. Interestingly,
      results also indicate that this relationship is moderated by both gender and
      parity, suggesting demographic and life course factors can impede or encourage
      post-marital union formation.

PMID- 23148125
TI  - A genome-wide study shows a limited contribution of rare copy number variants to
      Alzheimer's disease risk.
AB  - We assessed the role of rare copy number variants (CNVs) in Alzheimer's disease
      (AD) using intensity data from 3260 AD cases and 1290 age-matched controls from
      the genome-wide association study (GWAS) conducted by the Genetic and
      Environmental Risk for Alzheimer's disease Consortium (GERAD). We did not observe
      a significant excess of rare CNVs in cases, although we did identify duplications
      overlapping APP and CR1 which may be pathogenic. We looked for an excess of CNVs
      in loci which have been highlighted in previous AD CNV studies, but did not
      replicate previous findings. Through pathway analyses, we observed suggestive
      evidence for biological overlap between single nucleotide polymorphisms and CNVs
      in AD susceptibility. We also identified that our sample of elderly controls
      harbours significantly fewer deletions >1 Mb than younger control sets in
      previous CNV studies on schizophrenia and bipolar disorder (P = 8.9 * 10(-4) and
      0.024, respectively), raising the possibility that healthy elderly individuals
      have a reduced rate of large deletions. Thus, in contrast to diseases such as
      schizophrenia, autism and attention deficit/hyperactivity disorder, CNVs do not
      appear to make a significant contribution to the development of AD.

PMID- 23148130
TI  - Comparing the Glance Patterns of Older versus Younger Experienced Drivers:
      Scanning for Hazards while Approaching and Entering the Intersection.
AB  - Older drivers are known to look less often for hazards when turning at T
      intersections or at four way intersections. The present study is an extension of
      Romoser & Fisher (2009) and attempts to further analyze the differences in
      scanning behavior between older and experienced younger drivers in intersections.
      We evaluated four hypotheses that attempt to explain the older drivers' failure
      to properly scan in intersections: difficulty with head movements, decreases in
      working memory capacity, increased distractibility, and failure to recall
      specific scanning patterns. To test these hypotheses, older and younger
      experienced drivers' point-of-gaze was monitored while they drove a series of
      simulated intersections with hidden hazards outside of the turning path. Our
      results suggest that none of these hypotheses can fully explain our finding that
      older adults are more likely to remain fixated on their intended path of travel
      and look less than younger drivers towards other areas where likely hazards might
      materialize. Instead, the results support a complementary hypothesis that at
      least some of the difficulties older adults have scanning intersections are due
      to a specific attentional deficit in the older drivers' ability to inhibit what
      has become their prepotent goal of monitoring the vehicle's intended path of
      travel, thereby causing older drivers to fail to scan hazardous areas outside
      this intended path of travel.

PMID- 23148131
TI  - Reply to Comment on "Sloppy models, parameter uncertainty, and the role of
      experimental design"

PMID- 23148132
TI  - Laparoscopic splenic biopsy in dogs and cats: 15 cases (2006-2008).
AB  - This retrospective study describes a technique and evaluates outcome associated
      with laparoscopic splenic biopsy in dogs and cats. Medical records of dogs (n =
      10) and cats (n = 5) that had a laparoscopic splenic biopsy performed as part of
      their diagnostic evaluation for systemic disease were evaluated. Splenic biopsies
      were performed with the patient in dorsal recumbency using a two-portal approach.
      In some cases, concurrent organ biopsy was also performed. A pair of 5 mm cup
      biopsy forceps was used for biopsy collection, and an absorbable gelatin
      hemostatic sponge was placed at the biopsy site to aid in hemostasis. All
      patients recovered without major complications. Conversion to an open surgical
      approach was not required. Median survival time was 180 days, and nine patients
      were alive at the time of manuscript preparation. Four patients were diagnosed
      with neoplasia; however, only one had neoplasia involving the spleen. Median
      survival time for the nonneoplasia group (n = 11) was 300 days. Eight of those
      patients were alive at time of manuscript preparation. Minimal morbidity was
      observed in this cohort of clinical patients. Histopathology may be preferred
      over cytology in some clinical situations, and laparoscopic splenic biopsy
      provides a minimally invasive diagnostic option.

PMID- 23148133
TI  - UTIs in small animal patients: part 1: etiology and pathogenesis.
AB  - Understanding how urinary tract infections (UTIs) can occur and how to classify
      them can help the practitioner to make a plan for treatment. This review
      summarizes the etiology, pathogenesis, and host defense mechanisms associated
      with bacterial UTIs in dogs and cats. UTIs in Small Animal Patients: Part 2:
      Diagnosis, Treatment, and Complications will appear in the March/April 2013 issue
      of the Journal of the American Animal Hospital Association.

PMID- 23148134
TI  - Effect of a combined aspiration and core biopsy technique on quality of core bone
      marrow specimens.
AB  - For cases requiring both a bone marrow aspirate and core biopsy, using the same
      needle and site (i.e., a combined technique) can decrease time, expense, and
      discomfort compared with the independent (direct) collection of each specimen.
      The benefits of the combined approach should not be achieved at the expense of
      specimen quality. In this study, core bone marrow samples obtained from the
      proximal humerus of 26 dogs by a combined technique immediately posteuthanasia
      were compared with core samples obtained directly from the opposite humerus. Both
      core samples from each dog were compared for relative overall quality. Biopsies
      were unsuccessful in four dogs using the combined technique and in one dog by the
      direct technique. Marrow length was shorter and hemorrhage artifact was more
      common using the combined technique. There were no differences in cellularity,
      megakaryocyte count, the myeloid/erythroid ratio (M/E ratio), iron stores, or
      diagnostic quality. Direct core biopsy remains the ideal technique; however, the
      degree of compromise was small in the samples obtained from the combined
      technique. For clinical patients, the advantages of the combined technique must
      continue to be weighed against potential loss of diagnostic sensitivity.

PMID- 23148135
TI  - Persistent regurgitation in four dogs with caudal esophageal neoplasia.
AB  - Esophageal neoplasia is an uncommon, but important, consideration for acute and
      chronic regurgitation and megaesophagus in dogs. The diagnosis can be
      challenging, and treatment options are often limited. This case series describes
      four dogs with regurgitation secondary to caudal esophageal masses. All dogs
      presented with regurgitation, and three of the four dogs had radiographically
      apparent megaesophagus. In all dogs, ancillary diagnostics revealed the presence
      of a caudal esophageal mass resulting in esophageal obstruction, and all mass
      lesions were histopathologically confirmed to be neoplastic. Treatment responses
      were variable, with one dog still alive 37 mo postdiagnosis at the time of
      manuscript preparation.

PMID- 23148136
TI  - Treatment of afibrinogenemia in a chihuahua.
AB  - This report discusses the diagnosis and treatment of afibrinogenemia in a
      Chihuahua. Prolongations of prothrombin time (PT), activated partial
      thromboplastin time (aPTT), and thrombin clotting time (TCT) together with
      fibrinogen assay results of either no or trace amounts of fibrinogen support a
      diagnosis of afibrinogenemia. Differential diagnoses include common
      coagulopathies, liver failure, and disseminated intravascular coagulation (DIC).
      Either aggressive cryoprecipitate or plasma transfusions are required to treat
      afibrinogenemia. The current guidelines for treatment of coagulopathies include
      plasma transfusions (either 15-30 mL/kg or until both PT and aPTT are
      normalized). This report describes a case in which bleeding persisted 2 days
      after standard plasma transfusion levels were administered and PT and aPTT levels
      had normalized. In this case, the bleeding was stabilized for up to 2 mo after
      administering > 54 mL/kg plasma. In human medicine, either cryoprecipitate or
      fibrinogen concentrate is used to increase blood fibrinogen levels to 100 mg/dL
      for minor bleeding and 200 mg/dL for major bleeding. Further studies are needed;
      however, the author of this report suggests that aggressive transfusions and
      monitoring are needed in veterinary afibrinogenemia cases.

PMID- 23148137
TI  - An intrapericardial technique for PDA ligation: surgical description and clinical
      outcome in 35 dogs.
AB  - A number of surgical techniques have been reported for dissection and ligation of
      patent ductus arteriosi (PDAs) in dogs. The objectives of this study were to
      provide a detailed description of an intrapericardial technique for PDA
      dissection and ligation and to report the clinical outcome of that technique in
      dogs. Medical records of 35 dogs were retrospectively reviewed for signalment,
      clinical signs, echocardiographic findings, surgical time, intra- and
      postoperative complications, and completeness of ductal closure. Median surgery
      time was 60 min (range, 35-125 min). Neither intraoperative nor postoperative
      complications occurred. Within 48 hr of surgery, the continuous left basilar
      heart murmur was absent in all dogs, and complete echocardiographic closure was
      confirmed in 29 of 32 dogs. Residual flow was identified echocardiographically in
      three dogs within 48 hr of surgery. Residual flow was decreased in one dog at 1
      mo, which resolved within 33 mo. One dog had mild residual flow postoperatively
      but did not return for follow-up. The intrapericardial technique was successful
      for PDA dissection and ligation and had a lower rate (6%) of echocardiographic
      residual flow compared with previously reported techniques.

PMID- 23148138
TI  - Comparison of two portable lactate meters in dogs.
AB  - The objective of this study was to compare two portable lactate analyzers for
      testing canine patients in a clinical setting with a previously accepted
      methodology for measuring plasma lactate. Between Jan 1, 2005 and Jun 1, 2006,
      all samples were analyzed using two different portable analyzers (devices A and
      B), and 86 of those samples were also analyzed by a reference laboratory (REF).
      The concordance correlation coefficient (CCC) for device A and the REF was 0.949
      (95% confidence interval [95% CI], 0.923-0.966). For device B and REF, the CCC
      was 0.990 (95% CI, 0.985-0.993). Only 8 of 85 samples (9.4%) exceeded a relative
      difference of 20% for device B (note that 1 of the 86 samples was not included
      because the lactate level fell below the detectable limit of device B), but 48 of
      85 samples (56.5%) exceeded a relative difference of 20% for device A. Both
      portable lactate analyzers appeared to be effective in detecting clinically
      significant elevations in plasma lactate compared with the REF but device B had
      better agreement. A positive correlation among all three analyzers existed;
      however, the analyzers do not yield directly interchangeable results.

PMID- 23148139
TI  - Assessment of dental abnormalities by full-mouth radiography in small breed dogs.
AB  - This study was performed to evaluate full-mouth radiographic findings to
      determine the prevalence of dental abnormalities and analyze the relationship
      between dental abnormalities and age in small breed dogs. Sixteen predetermined
      categories of abnormal radiographic findings were evaluated in 233 small breed
      dogs. In total, 9,786 possible permanent teeth could be evaluated. Of those,
      8,308 teeth were evaluated and abnormal radiographic findings were found in 2,458
      teeth (29.6%). The most common teeth with abnormal radiographic findings were the
      mandibular first molars (74.5% on the left and 63.9% on the right) and the
      maxillary fourth premolars (40.5% on the left and 38.2% on the right). Bone loss
      of any type (15.8%) was the most commonly detected radiographic abnormal finding
      among the 16 categories. Dental conditions with a genetic predisposition were
      frequently occurred in the mandibular premolar teeth. Shih tzu frequently had
      unerupted teeth and dentigerous cysts. Among the teeth with abnormal radiographic
      findings, 4.5%, 19.8%, and 5.3% were considered incidental, additional, and
      important, respectively. Findings that were only detected on radiographs, which
      were not noted on routine oral examination, were more common in older dogs. Full
      mouth radiographic evaluation should be performed to obtain important information
      for making accurate diagnoses.

PMID- 23148140
TI  - Systemic hypertension and hypertensive retinopathy following PPA overdose in a
      dog.
AB  - A 4 yr old spayed female Labrador retriever was examined 4 hr after ingesting an
      overdose of phenylpropanolamine (PPA). Clinical signs included anxiety,
      piloerection, mucosal ulceration, cardiac arrhythmia, mydriasis, and hyphema.
      Clinicopathologic abnormalities included elevated creatine kinase (CK) and
      aspartate aminotransferase (AST), proteinuria, and pigmenturia. Ventricular
      tachycardia and severe systemic hypertension were documented. Hyphema and retinal
      detachment were documented oculus uterque (OU). Phenoxybenzamine, sotalol, and
      esmolol resolved the ventricular tachycardia, and blood pressure was controlled
      with nitroprusside. All clinicopathologic and cardiac abnormalities resolved
      within 7 days, and ocular changes resolved within 1 mo. Monitoring of blood
      pressure and rapid pharmacologic intervention were successful in controlling
      hypertension secondary to PPA overdose and minimizing retinal damage.

PMID- 23148141
TI  - Duodenogastric intussusception with concurrent gastric foreign body in a dog: a
      case report and literature review.
AB  - A 3 yr old spayed female boxer weighing 22.8 kg was presented for severe, acute
      vomiting and tenesmus. Tachycardia, tachypnea, dehydration, and abdominal pain
      were present on physical examination. Abdominal radiographs showed a foreign
      object (golf ball) in the fundus of the stomach, and a larger, round, soft-tissue
      opacity mass in the region of the pylorus. Endoscopic removal of the foreign
      object was unsuccessful. A large soft-tissue mass (duodenogastric
      intussusception) was visualized with endoscopy, but was not correctly diagnosed
      until surgery. A midline exploratory celiotomy was performed and the
      duodenogastric intussusception was diagnosed and manually reduced. Severe pyloric
      wall edema and minimal bruising were present. A routine fundic gastrotomy was
      performed and the foreign object was removed. A right-sided incisional gastropexy
      and duodenopexy were performed in attempt to prevent recurrence of the
      intussusception. The dog was discharged from the hospital 38 hrs after surgery,
      and was normal on follow-up 1 yr after surgery. The dog in this report is the
      sixth documented case of duodenogastric/pylorogastric intussusception in the
      veterinary literature. This is the first reported case with a concurrent gastric
      foreign body and endoscopic visualization of the intussusception.

PMID- 23148105
TI  - Heterogeneity in outcomes of treated HIV-positive patients in Europe and North
      America: relation with patient and cohort characteristics.
AB  - BACKGROUND: HIV cohort collaborations, which pool data from diverse patient
      cohorts, have provided key insights into outcomes of antiretroviral therapy
      (ART). However, the extent of, and reasons for, between-cohort heterogeneity in
      rates of AIDS and mortality are unclear. METHODS: We obtained data on adult HIV
      positive patients who started ART from 1998 without a previous AIDS diagnosis
      from 17 cohorts in North America and Europe. Patients were followed up from 1
      month to 2 years after starting ART. We examined between-cohort heterogeneity in
      crude and adjusted (age, sex, HIV transmission risk, year, CD4 count and HIV-1
      RNA at start of ART) rates of AIDS and mortality using random-effects meta
      analysis and meta-regression. RESULTS: During 61 520 person-years, 754/38 706
      (1.9%) patients died and 1890 (4.9%) progressed to AIDS. Between-cohort variance
      in mortality rates was reduced from 0.84 to 0.24 (0.73 to 0.28 for AIDS rates)
      after adjustment for patient characteristics. Adjusted mortality rates were
      inversely associated with cohorts' estimated completeness of death ascertainment
      [excellent: 96-100%, good: 90-95%, average: 75-89%; mortality rate ratio 0.66
      (95% confidence interval 0.46-0.94) per category]. Mortality rate ratios
      comparing Europe with North America were 0.42 (0.31-0.57) before and 0.47 (0.30
      0.73) after adjusting for completeness of ascertainment. CONCLUSIONS:
      Heterogeneity between settings in outcomes of HIV treatment has implications for
      collaborative analyses, policy and clinical care. Estimated mortality rates may
      require adjustment for completeness of ascertainment. Higher mortality rate in
      North American, compared with European, cohorts was not fully explained by
      completeness of ascertainment and may be because of the inclusion of more
      socially marginalized patients with higher mortality risk.

PMID- 23148143
TI  - Therapeutic Advances in Endocrinology and Metabolism: new crossroads in
      innovation, research, and clinical practice.

PMID- 23148142
TI  - Psychotropic effects of antimicrobials and immune modulation by psychotropics:
      implications for neuroimmune disorders.
AB  - Antimicrobial compounds and psychotropic medications often share overlapping
      mechanisms of actions and pharmacological effects. The immune system appears to
      be an important site of interaction as several antimicrobials display
      neurological and, at times, direct psychotropic effects, while psychotropics have
      shown significant immunomodulatory properties. The isoniazid class of antibiotics
      for example has been shown to possess monoamine oxidase activity, while selective
      serotonin reuptake inhibitors have shown significant effects on leukocyte
      populations. As the importance of the immune system's role in CNS homeostasis and
      disease continues to move to the forefront of neuropsychiatric research, these
      shared pharmacological effects may provide an important insight, elucidating the
      complexities in neuroimmune pathophysiology and guiding the development of
      potential treatments.

PMID- 23148144
TI  - Advances in the treatment of prediabetes.
AB  - Type 2 diabetes mellitus (T2DM) is epidemic in most developed and many developing
      countries. Owing to the associated morbidity, mortality and high costs of care,
      T2DM is an important global public health challenge and target for prevention.
      Patients at high risk for T2DM (referred to as having prediabetes) can be easily
      identified based on fasting glucose levels or responses to an oral glucose
      tolerance test (OGTT). More recently, glycosylated hemoglobin (i.e. HbA1c, which
      is also termed A1C in the US) has also been introduced as a diagnostic tool for
      both prediabetes and diabetes. Such patients are also at risk for cardiovascular
      disease (CVD). Since obesity and physical inactivity are important risk factors
      for T2DM, lifestyle interventions, emphasizing modest weight loss and increases
      in physical activity, should be recommended for most patients with prediabetes.
      Such interventions are safe and effective and also reduce risk factors for CVD. A
      number of oral antidiabetic agents have been shown to be effective at delaying
      onset of T2DM in patients with prediabetes. Thiazolidinediones (TZDs) are the
      most effective, reducing incident diabetes by up to 80%. Metformin, acarbose and
      orlistat also reduce incident diabetes, but their efficacy is much lower than the
      TZDs. Pharmacologic interventions may be appropriate for patients at particular
      risk for developing diabetes, but the benefits of treatment need to be balanced
      against the safety and tolerability of the intervention. If pharmacologic
      treatment is warranted, metformin should be considered first because of its
      favorable overall safety, tolerability, efficacy and cost profile.

PMID- 23148146
TI  - Therapeutic perspective: starting an angiotensin-converting enzyme inhibitor or
      angiotensin II receptor blocker in a diabetic patient.
AB  - There are extensive data confirming involvement of the renin-angiotensin system
      in microvascular and macrovascular complications of diabetes. Blockade of the
      system with angiotensin-converting enzyme (ACE) inhibitors or angiotensin II
      receptor blockers (ARBs) is regarded as the first-line approach to managing
      hypertension and end-organ protection in patients with diabetes. ACE inhibitors
      are still the preferred agents for most patients. Dose should be lower with renal
      impairment unless an agent which is not excreted by the kidneys is chosen. Dose
      should be titrated up to the maximum tolerated to optimize end-organ protection,
      and intermediate-acting agents should be given in a twice daily divided dose when
      higher doses are used. Electrolytes should be checked before commencing, 1-2
      weeks later, and after each dose increment. A modest decrease in estimated
      glomerular filtration rate (eGFR) and increase in creatinine often occurs with
      ACE inhibitors or ARBs. The agents may need to be discontinued if eGFR decreases
      by >15%, if creatinine increases by >20%, or if hyperkalemia develops. Cough
      occurs in 5-10% of patients taking ACE inhibitor, but not with ARBs. Angioedema
      is probably equally common with ACE inhibitor or ARBs. It is not widely
      appreciated that ACE inhibitors may precipitate hypoglycaemia in patients taking
      glucose-lowering medication. The combination of ACE inhibitor and ARB is not
      routinely indicated for either hypertension or end-organ protection. While
      patients should not be denied the undoubted benefits of these important classes
      of drugs, we should also guard against their indiscriminate use in patients with
      diabetes. We must also ensure that patients receive appropriate counselling and
      monitoring.

PMID- 23148145
TI  - Evidence for statin therapy in polycystic ovary syndrome.
AB  - Polycystic ovary syndrome (PCOS) is a common endocrine disorder in women of
      reproductive age group that is associated with increased cardiovascular risk. In
      addition to its lipid-lowering effects, statin therapy has shown been shown to
      have beneficial pleiotropic effects that may contribute to their reduction in
      cardiovascular morbidity and mortality. In this review, the effect of statins on
      PCOS is discussed with reference to the underlying potential mechanism of action.

PMID- 23148147
TI  - Endocrine and metabolic emergencies: hypocalcaemia.
AB  - Hypocalcaemia is a common electrolyte disturbance, especially in the inpatient
      setting. There are a wide variety of causes of hypocalcaemia and correct
      management depends on the underlying diagnosis. However, acute hypocalcaemia is
      associated with significant morbidity and mortality and should be managed as a
      medical emergency. Chronic care of the hypocalcaemic patient is also briefly
      described, as this is an important opportunity to reduce further admissions
      related to both hypocalcaemic and hypercalcaemic presentations.

PMID- 23148148
TI  - The metabolic syndrome: what's in a name?

PMID- 23148149
TI  - No accord for the ACCORD-Lipid trial results.

PMID- 23148150
TI  - Hydroxyoctadecadienoic acids: novel regulators of macrophage differentiation and
      atherogenesis.
AB  - Hydroxyoctadecadienoic acids (HODEs) are stable oxidation products of linoleic
      acid, the generation of which is increased where oxidative stress is increased,
      such as in diabetes. In early atherosclerosis, 13-HODE is generated in
      macrophages by 15-lipoxygenase-1. This enhances protective mechanisms through
      peroxisome proliferator-activated receptor (PPAR)-g activation leading to
      increased clearance of lipid and lipid-laden cells from the arterial wall. In
      later atherosclerosis, both 9-HODE and 13-HODE are generated nonenzymatically. At
      this stage, early protective mechanisms are overwhelmed and pro-inflammatory
      effects of 9-HODE, acting through the receptor GPR132, and increased apoptosis
      predominate leading to a fragile, acellular plaque. Increased HODE levels thus
      contribute to atherosclerosis progression and the risk of clinical events such as
      myocardial infarction or stroke. Better understanding of the role of HODEs may
      lead to new pharmacologic approaches to modulate their production or action, and
      therefore lessen the burden of atherosclerotic disease in high-risk patients.

PMID- 23148151
TI  - The evolving world of GLP-1 agonist therapies for type 2 diabetes.
AB  - The glucagon-like peptide-1 (GLP-1) agonist drugs have attractions as a treatment
      for type 2 diabetes since they positively alter a number of key
      pathophysiological defects. These include increasing insulin release, reducing
      glucagon release, slowing gastric emptying and reducing food intake. In numerous
      clinical trials these agents have been shown to reduce DCCT-aligned HbA(1c)
      between 0.8% and 1.1% in patients with moderately controlled type 2 diabetes,
      whilst also being associated with some weight loss. Whilst medium-term safety and
      side-effect profiles are now well established, there are as yet no long-term
      studies on the safety of this group of drugs. The place of the GLP-1 agonists in
      the treatment paradigm for type 2 diabetes will evolve over the next decade.

PMID- 23148153
TI  - Developing therapies for the metabolic syndrome: challenges, opportunities,
      and... the unknown.
AB  - Metabolic syndrome refers to a clustering of established and emerging
      cardiovascular disease risk factors within a single individual. The established
      risk factors, such as obesity, diabetes, dyslipidaemia and hypertension, and
      other emerging risk factors are closely related to central obesity (especially
      intra-abdominal adiposity) and insulin resistance. However, debate continues
      about the very existence of the metabolic syndrome. Despite the controversies,
      many existing and new therapies are targeting the metabolic syndrome and
      component risk factors. To date, no therapies have been approved specifically for
      treating the metabolic syndrome. In this article some of the challenges and
      opportunities in developing therapies for the metabolic syndrome are discussed.

PMID- 23148154
TI  - Something old, something new....

PMID- 23148152
TI  - Novel insights on diagnosis, cause and treatment of diabetic neuropathy: focus on
      painful diabetic neuropathy.
AB  - Diabetic neuropathy is common, under or misdiagnosed, and causes substantial
      morbidity with increased mortality. Defining and developing sensitive diagnostic
      tests for diabetic neuropathy is not only key to implementing earlier
      interventions but also to ensure that the most appropriate endpoints are employed
      in clinical intervention trials. This is critical as many potentially effective
      therapies may never progress to the clinic, not due to a lack of therapeutic
      effect, but because the endpoints were not sufficiently sensitive or robust to
      identify benefit. Apart from improving glycaemic control, there is no licensed
      treatment for diabetic neuropathy, however, a number of pathogenetic pathways
      remain under active study. Painful diabetic neuropathy is a cause of considerable
      morbidity and whilst many pharmacological and nonpharmacological interventions
      are currently used, only two are approved by the US Food and Drug Administration.
      We address the important issue of the 'placebo effect' and also consider
      potential new pharmacological therapies as well as nonpharmacological
      interventions in the treatment of painful diabetic neuropathy.

PMID- 23148155
TI  - Advances in the treatment of nonalcoholic fatty liver disease.
AB  - Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic
      liver disease in the Western world, and its prevalence is predicted to rise in
      the future in parallel with rising levels of obesity and type 2 diabetes
      mellitus. It is commonly associated with insulin resistance. Many patients have
      coexisting obesity, hypertension, dyslipidaemia or hyperglycaemia, and are at
      increased risk of developing cardiovascular disease. Although patients with
      simple steatosis have a good prognosis, a significant percentage will develop
      nonalcoholic steatohepatitis which may progress to cirrhosis, end-stage liver
      failure and hepatocellular carcinoma. Despite promising results from several
      pilot studies and small to medium randomized controlled trials, there is
      currently no pharmacological agent that is licensed for the treatment of NAFLD.
      At present the mainstay of treatment for all patients is lifestyle modification
      using a combination of diet, exercise and behavioural therapy. With recent
      advances in the understanding of the pathogenesis of NAFLD, the goal of treatment
      has shifted from simply trying to clear fat from the liver and prevent
      progressive liver damage to addressing and treating the metabolic risk factors
      for the condition. To reduce liver-related and cardiovascular morbidity and
      mortality, all patients with NAFLD should be invited to enrol in adequately
      powered, randomized controlled studies testing novel therapies, many of which are
      targeted at reducing insulin resistance or preventing progressive liver disease.
      Coexisting obesity, hypertension, dyslipidaemia or hyperglycaemia should be
      treated aggressively. Orlistat, bariatric surgery, angiotensin receptor blockers,
      statins, fibrates, metformin and thiazolidinediones should all be considered, but
      treatments should be carefully tailored to meet the specific requirements of each
      patient. The efficacy and safety of any new treatment, as well as its cost
      effectiveness, will need to be carefully evaluated before it can be advocated for
      widespread clinical use.

PMID- 23148157
TI  - Replication of cortisol circadian rhythm: new advances in hydrocortisone
      replacement therapy.
AB  - Cortisol has one of the most distinct and fascinating circadian rhythms in human
      physiology. This is regulated by the central clock located in the suprachiasmatic
      nucleus of the hypothalamus. It has been suggested that cortisol acts as a
      secondary messenger between central and peripheral clocks, hence its importance
      in the synchronization of body circadian rhythms. Conventional immediate-release
      hydrocortisone, either at twice- or thrice-daily doses, is not capable of
      replicating physiological cortisol circadian rhythm and patients with adrenal
      insufficiency or congenital adrenal hyperplasia still suffer from a poor quality
      of life and increased mortality. Novel treatments for replacement therapy are
      therefore essential. Proof-of-concept studies using hydrocortisone infusions
      suggest that the circadian delivery of hydrocortisone may improve biochemical
      control and life quality in patients lacking cortisol with an impaired cortisol
      rhythm. Recently oral formulations of modified-release hydrocortisone are being
      developed and it has been shown that it is possible to replicate cortisol
      circadian rhythm and also achieve better control of morning androgen levels.
      These new drug therapies are promising and potentially offer a more effective
      treatment with less adverse effects. Definite improvements clearly need to be
      established in future clinical trials.

PMID- 23148158
TI  - Endocrine and metabolic emergencies: thyroid storm.
AB  - Thyrotoxicosis is a common endocrine condition that may be secondary to a number
      of underlying processes. Thyroid storm (also known as thyroid or thyrotoxic
      crisis) represents the severe end of the spectrum of thyrotoxicosis and is
      characterized by compromised organ function. Whilst rare in the modern era, the
      mortality rate remains high, and prompt consideration of this endocrine
      emergency, with specific treatments, can improve outcomes.

PMID- 23148156
TI  - Role of metformin in the management of polycystic ovary syndrome.
AB  - Polycystic ovary syndrome is the most common endocrinological disorder affecting
      4-12% of women and also the most controversial. Metformin was logically
      introduced to establish the extent to which hyperinsulinaemia influences the
      pathogenesis of the condition. Early studies were very encouraging. Randomized
      controlled studies and several metaanalyses have changed the picture and put the
      drug that was once heralded as magic in a much contracted place. More work is
      needed to establish its right place in particular with regards to the prevention
      of many gestational and long-term complications.

PMID- 23148159
TI  - The rejuvenation of testosterone: philosopher's stone or Brown-Sequard Elixir?

PMID- 23148160
TI  - Testosterone therapy for reduced libido in women.
AB  - Modest benefit has been shown from transdermal testosterone therapy given to
      postmenopausal women with reduced sexual desire. An increased frequency of
      satisfying sexual encounters and intensity of sexual desire and response has been
      shown in medically and psychiatrically healthy women able to have 2-3 satisfying
      sexual experiences each month before therapy commences. Women more clearly
      sexually dysfunctional in keeping with currently proposed definitions of sexual
      disorder have not been studied. Numerous factors are known to influence women's
      sexual desire with mood and feelings towards the partner showing the most robust
      associations. How to identify women whose low desire might stem from low
      testosterone activity remains unknown: neither serum levels of testosterone nor
      its metabolites correlate with desire or function. Production of androgens in the
      brain, sensitivity of the androgen receptors, and activity of cofactors are all
      potentially relevant confounds. The long-term safety of systemic testosterone
      with or without estrogen is unknown but necessary as women's sexual lives tend to
      endure as long as there is an active partner.

PMID- 23148161
TI  - Free fatty acid receptors: emerging targets for treatment of diabetes and its
      complications.
AB  - Fatty acids (FAs) are important as metabolic substrates and as structural
      components of biological membranes. However, they also function as signalling
      molecules. Recently, a series of G protein-coupled receptors (GPRs) for FAs has
      been described and characterized. These receptors have differing specificities
      for FAs of differing chain length and degree of saturation, for FA derivatives
      such as oleoylethanolamide, and for oxidized FAs. They are a critical component
      of the body's nutrient sensing apparatus, and small molecule agonists and
      antagonists of these receptors show considerable promise in the management of
      diabetes and its complications. Agonists of the long-chain free fatty acid
      receptors FFAR1 and GPR119 act as insulin secretagogues, both directly and by
      increasing incretins. Although, drugs acting at short-chain FFA receptors (FFAR2
      and FFAR3) have not yet been developed, they are attractive targets as they
      regulate nutrient balance through effects in the intestine and adipose tissue.
      These include regulation of the secretion of cholecystokinin, peptide YY and
      leptin. Finally, GPR132 is a receptor for oxidized FAs, which may be a sensor of
      lipid overload and oxidative stress, and which is involved in atherosclerosis.
      Regulation of its signalling pathways with drugs may decrease the macrovascular
      risk experienced by diabetic patients. In summary, FA receptors are emerging drug
      targets that are involved in the regulation of nutrient status and carbohydrate
      tolerance, and modulators of these receptors may well figure prominently in the
      next generation of antidiabetic drugs.

PMID- 23148162
TI  - Therapeutic approaches for lysosomal storage diseases.
AB  - The lysosomal storage disorders (LSDs) comprise a heterogeneous group of inborn
      errors of metabolism characterized by tissue substrate deposits, most often
      caused by a deficiency of the enzyme normally responsible for catabolism of
      various byproducts of cellular turnover. Individual entities are typified by
      involvement of multiple body organs, in a pattern reflecting the sites of
      substrate storage. It is increasingly recognized that one or more processes, such
      as aberrant inflammation, dysregulation of apoptosis and/or defects of autophagy,
      may mediate organ dysfunction or failure. Several therapeutic options for various
      LSDs have been introduced, including hematopoietic stem cell transplantation,
      enzyme replacement therapy and substrate reduction therapy. Additional strategies
      are being explored, including the use of pharmacological chaperones and gene
      therapy. Most LSDs include a variant characterized by primary central nervous
      system (CNS) involvement. At present, therapy of the CNS manifestations remains a
      major challenge because of the inability to deliver therapeutic agents across the
      intact blood-brain barrier. With improved understanding of underlying disease
      mechanisms, additional therapeutic options may be developed, complemented by
      various strategies to deliver the therapeutic agent(s) to recalcitrant sites of
      pathology such as brain, bones and lungs.

PMID- 23148163
TI  - Primary hyperparathyroidism: just how 'primary' is it really?

PMID- 23148164
TI  - New perspectives in the management of primary hyperparathyroidism.
AB  - Primary hyperparathyroidism (PHPT) is a biochemical syndrome caused by the
      inappropriate or unregulated overproduction of parathyroid hormone, Leading to
      hypercalcae-mia. It was previously considered a relatively rare disorder, with
      clinical manifestations dominated by renal and/or bone disease. However, in
      modern times the diagnosis is most frequently recognized coincidentally on
      biochemical testing in patients evaluated for unrelated complaints.
      Parathyroidectomy is the only curative treatment for PHPT, with improved outcomes
      in symptomatic patients following this procedure. However, surgical intervention
      in patients with no clear clinical features remains controversial. The National
      Institutes for Health (NIH) have developed consensus guidelines giving specific
      indications for when surgery is recommended in patients with asymptomatic PHPT.
      This article examines the impact of treatment on asymptomatic PHPT, focusing on
      bone disease, neurocognitive function, quality of Life, cardiovascular disease
      and mortality. Medical treatment options, including bisphospho-nates and
      cinacalcet, are also discussed.

PMID- 23148166
TI  - Endocrine and metabolic emergencies: hypercalcaemia.
AB  - Hypercalcaemia is commonly seen in the context of parathyroid dysfunction and
      malignancy and, when severe, can precipitate Life-threatening sequelae. The
      differential of hypercalcaemia is broad and can be categorized based on
      parathyroid hormone (PTH) Levels. The acute management of severe hypercalcaemia
      is discussed along with a brief review of therapeutic advances in the field.

PMID- 23148167
TI  - Hyperglycemia in-hospital management.

PMID- 23148165
TI  - Testosterone and the metabolic syndrome.
AB  - Metabolic syndrome and testosterone deficiency in men are closely Linked.
      Epidemiological studies have shown that Low testosterone Levels are associated
      with obesity, insulin resistance and an adverse Lipid profile in men. Conversely
      in men with metabolic syndrome and type 2 diabetes have a high prevalence of
      hypogonadism. Metabolic syndrome and Low testosterone status are both
      independently associated with increased all-cause and cardiovascular mortality.
      Observational and experimental data suggest that physiological replacement of
      testosterone produces improvement in insulin resistance, obesity, dyslipidae-mia
      and sexual dysfunction along with improved quality of Life. However, there are no
      Long-term interventional studies to assess the effect of testosterone replacement
      on mortality in men with Low testosterone Levels. This article reviews the
      observational and interventional clinical data in relation to testosterone and
      metabolic syndrome.

PMID- 23148168
TI  - Prevention of Type 1 Diabetes Mellitus using a Novel Vaccine.
AB  - Type 1 diabetes mellitus (T1DM) affects 1 in 300 people and the incidence of the
      disease is rising worldwide. T1DM is caused by chronic autoimmune destruction of
      the insulin-producing beta-cells. The exact etiology and primary auto-antigen are
      not yet known. The autoimmune, chronic, and progressive nature of the disease
      raises the possibility of intervention, preferably by slowing down or stopping
      the destruction of the beta-cells as early as the prediabetic stage. Since the
      1980s, several attempts have been made to maintain beta-cell function using
      immunosuppressive agents, immune modulation such as plasmapheresis, cytokine
      therapy, or antibody treatment. These agents were not diabetes specific; the
      occasionally observed beneficial effect did not compensate for the often very
      severe side effects. According to the latest assumption, the administration of
      diabetes-specific auto-antigens can elicit tolerance, which can prevent the
      destruction of the beta-cells, hopefully without serious side effects. The
      authors summarize current understanding of the immunology of T1DM, review the
      trials on prevention, and discuss their vaccination study.

PMID- 23148169
TI  - Near-Normalization of Glucose and Microvascular Diabetes Complications: Data from
      ACCORD and ADVANCE.
AB  - OBJECTIVE: To compare results of clinical trials that assessed the impact of near
      normalization of glucose on microvascular complications in type 2 diabetes.
      METHODS: ACCORD (N = 10,234) and ADVANCE (N = 11,140) tested the hypothesis that
      near-normalization of glucose reduces microvascular complications in adults with
      established type 2 diabetes. Differences in incidence rates (intensive versus
      standard glucose control) for specific microvascular complications are expressed
      as 'number needed to treat' (NNT) to prevent one microvascular complication. The
      impact of blood pressure (BP) control and fenofibrate use on microvascular
      complications was also assessed. RESULTS: In ADVANCE, near-normalization of
      glucose reduced new or worsening nephropathy (NNT = 77 for 5 years to prevent one
      occurrence), but not eye or foot complications. In ACCORD, near-normalization of
      glucose did not reduce prespecified composite measures of advanced microvascular
      complications, and impact on secondary microvascular outcomes was mixed. The
      ancillary ACCORD Eye Study found reduced progression in retinopathy with near
      normalization of glucose (NNT = 32 for 4 years), and with blinded fenofibrate
      therapy (NNT = 27 for 4 years), but neither intervention reduced vision loss.
      ADVANCE showed a benefit of intensive BP control (mean BP 133/70 mmHg) on
      microvascular complications, independent of glucose control. CONCLUSIONS: End
      stage microvascular complications were not altered by near-normalization of
      glucose. Some early manifestations of microvascular complications were reduced,
      with inconsistencies across studies in which were affected. These early and
      inconsistent micro-vascular effects must be weighed against significantly
      increased severe hypoglycemia, weight gain, and (in ACCORD) increased total
      mortality (NNT = 94 for 3.5 years for one excess death) consistently found in all
      prespecified patient subgroups. Alternative clinical strategies, such as moderate
      BP control or fenofibrate treatment may reduce microvascular complications
      independent of glucose control. The data strongly support personalized glucose
      control goals based on clinical factors and patient preferences for outcomes.

PMID- 23148170
TI  - Review of therapeutic advances in diabetic retinopathy.
AB  - Diabetic retinopathy is a common microvascular complication of prolonged
      diabetes. It is one of the leading causes of vision loss in working age adults
      and a significant source of morbidity. To reduce the incidence and severity of
      diabetic retinopathy, it is important to identify patients at risk and promptly
      implement intensive glycemic and hypertensive control. To date, there are many
      interventions that can limit moderate and severe vision loss in people with
      diabetes, including laser photocoagulation, vitrectomy surgery, and intravitreal
      pharmacological injections. This review aims to define the different stages of
      diabetic retinopathy and the important therapeutic advances developed to address
      the major causes of vision loss in each stage.

PMID- 23148171
TI  - Challenges in beta(3)-Adrenoceptor Agonist Drug Development.

PMID- 23148173
TI  - Endocrine and metabolic emergencies: hypoglycaemia.
AB  - Hypoglycaemia is rare in healthy individuals owing to the numerous elegant
      hormonal and neuronal mechanisms that maintain glucose homeostasis. Glucose is an
      obligate metabolic fuel for cerebral tissue and therefore hypoglycaemia, if
      uncorrected, can have disastrous consequences including death. Clinical
      hypoglycaemia is defined as a plasma (or serum) glucose concentration low enough
      to cause symptoms and/or signs, including impairment of brain function. However,
      no single plasma (or serum) glucose concentration categorically defines
      hypoglycaemia. Hypoglycaemia is probably the most common endocrine and metabolic
      emergency in clinical practice. The overwhelming majority of occurrences of
      hypoglycaemia occur in patients with diabetes, either as a result of treatment
      induced hypoglycaemia and/or abnormalities that affect the normal
      counterregulatory response to hypoglycaemia. The differential for nondiabetes
      associated hypoglycaemia is broad and includes insulinoma, drugs, hormone
      deficiencies, and critical illness. The acute management of hypoglycaemia is
      discussed along with a review of the pathophysiology and aetiology of this
      commonly encountered clinical problem.

PMID- 23148174
TI  - Reaction to the recent publication by rosemary basson entitled 'testosterone
      therapy for reduced libido in women'.

PMID- 23148175
TI  - Response to dr simes and dr snabes.

PMID- 23148176
TI  - Effect of Natural Products on Commercial Oral Antidiabetic Drugs in Enhancing 2
      Deoxyglucose Uptake by 3T3-L1 Adipocytes.
AB  - OBJECTIVE: The management of diabetes with insulin and synthetic oral
      hypoglycemic drugs (OHDs) can produce serious side effects and in addition fails
      to prevent diabetes-related complications in many patients. A new diabetes
      management strategy is needed that is more effective and has fewer side effects.
      METHODS: This paper analyzes the dose- and time-dependent effect of three
      phytochemicals: berberine, arecoline and vanillic acid, and two antidiabetic
      drugs: 2,4-thiazolidinedione (TZD) and metformin, on the uptake of 2-deoxyglucose
      (2DG) by 3T3-L1 adipocytes. The interactions of the phytochemicals with the OHDs
      were analyzed with isobolograms and the combination index. RESULTS: TZD and
      berberine increased 2DG uptake by 3.3-fold (with respect to control) at 15 MUM
      and 25 MUM, respectively. The same concentrations of arecoline and vanillic acid
      increased 2DG uptake by 3.2-and 2.9-fold, respectively, when compared with the
      basal level. Berberine and arecoline acted synergistically with both the OHDs,
      whereas vanillic acid had an additive interaction with TZD and an antagonistic
      interaction with metformin. Arecoline significantly increased the translocation
      of GLUT4 via the PPAR(gamma) pathway, whereas berberine and vanillic acid did
      this via the AMPK-dependent pathway. CONCLUSIONS: These phytochemicals
      significantly reduced the expression of the enzymes involved in fatty acid and
      cholesterol synthesis, indicating that they might help prevent the secondary
      complications of diabetes. The current study suggests that berberine and
      arecoline could allow dosage reduction of OHDs, which could also lead to a
      reduction in the toxicity and side effects caused by OHDs.

PMID- 23148172
TI  - beta(3) Receptors: Role in Cardiometabolic Disorders.
AB  - Pharmacological and molecular approaches have shown that an atypical beta
      adrenoceptor (AR), called beta(3)-AR, that is distinct from beta(1)-ARs and
      beta(2)-ARs, exists in some tissues in heterogeneous populations such as beta(3a)
      ARs and beta(3b)-ARs. beta(3)-ARs belong to a superfamily of receptors linked to
      guanine nucleotide binding proteins (G proteins). The beta(3)-AR gene contains
      two introns whereas the beta(1)-AR and beta(2)-AR genes are intronless, leading
      to splice variants. beta(3)-ARs can couple to G(i) and G(s) and they are reported
      to be present in brown adipose tissue, vasculature, the heart, among other
      tissues. beta(3)-ARs cause vasodilation of microvessels in the islets of
      Langerhans and may participate in the pathogenesis of cardiac failure, during
      which modification of beta(1)-AR and beta(2)-AR expression occurs. The
      development of beta(3)-AR agonists has led to the elaboration of promising new
      drugs, including antiobesity and antidiabetic drugs. This article reviews the
      various pharmacological actions of beta(3)-ARs and their clinical implications
      for diabetes and cardiovascular diseases.

PMID- 23148178
TI  - Sapropterin hydrochloride: enzyme enhancement therapy for phenylketonuria.
AB  - Phenylketonuria (PKU) is an inherited disorder of amino acid metabolism caused by
      deficiency of the enzyme phenylalanine hydroxylase (PAH). Historically PKU was a
      common genetic cause of severe learning difficulties and developmental delay, but
      with the introduction of newborn screening and early dietary management, it has
      become a treatable disease and people born with PKU should now have IQs and
      achievements similar to their peers. Dietary treatment, however, involves
      lifestyle changes that pervade most aspects of daily life for an individual and
      their family. A simple pharmacological treatment for PKU would have a great
      appeal. Sapropterin hydrochloride is a synthetic form of tetrahydrobiopterin, the
      cofactor for PAH. A proportion of mutant PAH enzymes show enhanced activity in
      the presence of pharmacological doses of sapropterin and, for some patients with
      milder forms of PKU, sapropterin can effectively lower plasma phenylalanine
      levels. This article discusses the potential place for sapropterin in the
      management of PKU and how this expensive orphan drug is being integrated into
      patient care in different healthcare systems.

PMID- 23148177
TI  - Management of amiodarone-related thyroid problems.
AB  - Amiodarone is a highly effective and well-established antiarrrhythmic drug. It
      can be used to treat supraventricular and ventricular tachyarrhythmias and has
      the added advantage of being well tolerated in patients with impaired left
      ventricular systolic function with a low incidence of arrhythmic events, such as
      torsades de pointes. However, owing to its marked lipid affinity, it is highly
      concentrated in tissues and is linked to a number of adverse effects, including
      thyroid dysfunction. Amiodarone can lead to both hypothyroidism (amiodarone
      induced hypothyroidism) and less commonly hyperthyroidism (amiodarone-induced
      thyrotoxicosis) and relates to high iodine content within the molecule as well as
      to several unique intrinsic properties of amiodarone. Dronedarone is a recently
      approved antiarrhythmic drug. It is structurally very similar to amiodarone,
      however the iodine moiety, present with amiodarone has been removed and replaced
      with a methylsulfonamide group to reduce fat solubility and adverse effects. We
      present an overview of the effects of amiodarone on thyroid function and the
      treatment options available, as well as a brief insight into dronedarone and its
      potential as an alternative to amiodarone.

PMID- 23148180
TI  - Dedicated to evidence-based medicine and the evaluation of new therapeutic
      approaches in the field.

PMID- 23148179
TI  - Current concepts in graves' disease.
AB  - Graves' disease is the most common cause of hyperthyroidism in the developed
      world. It is caused by an immune defect in genetically susceptible individuals in
      whom the production of unique antibodies results in thyroid hormone excess and
      glandular hyperplasia. When unrecognized, Graves' disease impacts negatively on
      quality of life and poses serious risks of psychosis, tachyarrhythmia and cardiac
      failure. Beyond the thyroid, Graves' disease has diverse soft-tissue effects that
      reflect its systemic autoimmune nature. Thyroid eye disease is the most common of
      these manifestations and is important to recognise given its risk to vision and
      potential to deteriorate in response to radioactive iodine ablation. In this
      review we discuss the investigation and management of Graves' disease, the recent
      controversy regarding the hepatotoxicity of propylthiouracil and the emergence of
      novel small-molecule thyroid-stimulating hormone (TSH) receptor ligands as
      potential targets in the treatment of Graves' disease.

PMID- 23148182
TI  - Adverse orthopedic effect of exogenous estrogens on men undergoing cross-gender
      hormonal therapy.

PMID- 23148181
TI  - Effect of genetic polymorphisms on the development of secondary failure to
      sulfonylurea in egyptian patients with type 2 diabetes.
AB  - OBJECTIVE: This study investigated the possibility that genetic factors, such as
      polymorphism of K inward rectifier subunit (Kir6.2), E23K, and Arg(972)
      polymorphism of insulin receptor sub-strate-1 (IRS-1), may predispose patients to
      sulfonylurea failure. METHODS: A total of 100 unrelated Egyptian patients with
      type 2 diabetes were recruited. They were divided into two equal groups: group I
      consisted of patients with secondary failure to sulfonylurea (hemoglobin A(1c) >=
      8% despite sulfonylurea therapy) while group II consisted of patients whose
      condition was controlled with oral therapy. RESULTS: Of all the patients, 45% and
      14% were carriers of the K allele and Arg(972) variants respectively. The
      frequency of the K allele was 34% among patients with diabetes that was
      controlled with oral therapy and 56% among patients with secondary failure to
      sulfonylurea. The frequency of the Arg(972) IRS-1 variant was 6% among patients
      with diabetes controlled with oral therapy and 22% among patients with secondary
      failure. CONCLUSION: The E23K variant of the Kir6.2 gene and Arg(972) IRS-1
      variants are associated with increased risk for secondary failure to
      sulfonylurea.

PMID- 23148183
TI  - Seizure associated with zoledronic Acid therapy: side-effects or coincidental
      finding?

PMID- 23148185
TI  - The prospect of induced pluripotent stem cells for diabetes mellitus treatment.
AB  - A continuous search for a permanent cure for diabetes mellitus is underway with
      several remarkable discoveries over the past few decades. One of these is the
      potential of pancreatic stem/progenitor cells to rejuvenate functional beta
      cells. However, the existence of these cell populations is still obscure and a
      lack of phenotype characterization hampers their use in clinical settings.
      Cellular reprogramming through induced pluripotent stem (iPS) cell technology can
      become an alternative strategy to generate insulin-producing cells in a
      relatively safe (autologous-derived cells, thus devoid of rejection risk) and
      efficient way (high cellular proliferation) but retain a precise morphological
      and genetic composition, similar to that of the native beta cells. iPS cell
      technology is a technique of transducing any cell types with key transcription
      factors to yield embryonic-like stem cells with high clonogenicity and is able to
      give rise into all cell lineages from three germ layers (endoderm, ectoderm, and
      mesoderm). This approach can generate beta-like pancreatic cells that are fully
      functional as proven by either in vitro or in vivo studies. This novel proof-of
      concept stem cell technology brings new expectations on applying stem cell
      therapy for diabetes mellitus in clinical settings.

PMID- 23148184
TI  - Thyroid cancer: pathogenesis and targeted therapy.
AB  - Therapeutic options for advanced, unresectable radioiodine-resistant thyroid
      cancers have historically been limited. Recent progress in understanding the
      pathogenesis of the various subtypes of thyroid cancer has led to increased
      interest in the development of targeted therapies, with potential strategies
      including angiogenesis inhibition, inhibition of aberrant intracellular signaling
      in the MAPK and PI3K/AKT/mTOR pathways, radioimmunotherapy, and redifferentiation
      agents. On the basis of a recent positive phase III clinical trial, the RET,
      vascular endothelial growth factor receptor (VEGFR), and epidermal growth factor
      receptor (EGFR) inhibitor vandetanib has received FDA approval as of April 2011
      for use in the treatment of advanced medullary thyroid cancer. Several other
      recent phase II clinical trials in advanced thyroid cancer have demonstrated
      significant activity, and multiple other promising therapeutic strategies are in
      earlier phases of clinical development. The recent progress in targeted therapy
      is already revolutionizing management paradigms for advanced thyroid cancer, and
      will likely continue to dramatically expand treatment options in the coming
      years.

PMID- 23148187
TI  - Editorial: Closing sale of innovative treatment options for the treatment of
      diabetes and metabolic disorders?

PMID- 23148186
TI  - An Endocrine Perspective of Nonalcoholic Fatty Liver Disease (NAFLD).
AB  - Endocrinologists are encountering patients with obesity-related complications
      such as metabolic syndrome (MetS) and type 2 diabetes mellitus (T2DM) on a daily
      basis. Nonalcoholic fatty liver disease (NAFLD) is a liver condition
      characterized by insulin resistance, hepatic steatosis and frequently T2DM. This
      is now the most common chronic liver condition in adults and is present in the
      majority of obese subjects. Liver fat accumulation may range from simple
      steatosis to severe steatohepatitis with hepatocyte necroinflammation (or
      nonalcoholic steatohepatitis [NASH]). Although the natural history is
      incompletely understood, NAFLD may lead to serious medical consequences ranging
      from cirrhosis and hepatocellular carcinoma to earlier onset of T2DM and
      cardiovascular disease (CVD). The diagnosis of NAFLD may be challenging because
      signs and symptoms are frequently absent or nonspecific, and thus easily missed.
      Liver aminotransferases may be helpful if elevated, but most times are normal in
      the presence of the disease. Liver imaging may assist in the diagnosis
      (ultrasound or MRI and spectroscopy) but a definitive diagnosis of NASH still
      requires a liver biopsy. This may change in the near future as novel biomarkers
      become available. Treatment of NAFLD includes aggressive management of associated
      cardiovascular risk factors and many times control of T2DM. Pioglitazone and
      vitamin E appear promising for patients with NASH, although long-term studies are
      unavailable. In summary, this review hopes to address the common clinical
      dilemmas that endocrinologists face in the diagnosis and management of NAFLD and
      increase awareness of a potentially serious medical condition.

PMID- 23148188
TI  - Serum adiponectin and resistin in relation to insulin resistance and markers of
      hyperandrogenism in lean and obese women with polycystic ovary syndrome.
AB  - OBJECTIVE: The role of insulin resistance in polycystic ovary syndrome (PCOS) has
      been established. However the role of adiponectin and resistin in the
      relationship between insulin resistance as markers of obesity and PCOS has not
      been conclusive. This study aims to determine the influence of the serum levels
      of adiponectin and resistin on PCOS, and assess possible correlations with the
      hormonal and metabolic parameters of the syndrome and obesity. METHODS: This
      study continued a case control study that had finished recruiting 24 subjects of
      reproductive women with PCOS as a case group, and 24 subjects of normal ovulatory
      reproductive women without hyperandrogenism as a control group. Further, only 18
      subjects of the control group had a body mass index (BMI) <25 kg/m(2) and were
      included the data analysis, whereas others were excluded. Therefore, these study
      data were divided into three groups. Twenty-four PCOS patients from the case
      group were allocated to two groups, A (n = 14) patients had PCOS + BMI >=25
      kg/m(2); B (n = 10) patients had PCOS + BMI <25 kg/m(2). Group C was the control
      group of 18 reproductive women without PCOS + BMI <25 kg/m(2). Blood samples were
      collected between day 3 and 5 of a spontaneous menstrual cycle, at 07:00 to
      09:00, after overnight fasting. Serum levels of follicle-stimulating hormone
      (FSH), luteinizing hormone (LH), total testosterone, prolactin, sex hormone
      binding globulin (SHBG), glucose, insulin, adiponectin and resistin were
      measured. RESULTS: Serum adiponectin levels were significantly decreased in group
      A compared with group B and group C. No significant difference existed in
      adiponectin between group B and group C. Homeostasis Model of Assessment-Insulin
      Resistance (HOMA-IR) value in group A was found to be significantly higher than
      group C, but no significant differences were found between group B and group C or
      between group A and group B. There was no significant difference in serum
      resistin between all groups, nevertheless the resistin-to-adiponectin (R:A) ratio
      was significantly decreased in group A compared with groups B and C. In a
      multiple regression model, BMI, testosterone and insulin resistance were the
      major determinants of hypoadiponectinemia. However, only BMI was the major
      determinant of the resistin represented by the R:A ratio. CONCLUSIONS: Serum
      adiponectin levels and the ratio of resistin to adiponectin levels are reduced in
      obese women with PCOS. These results suggest that, by reducing adiponectin serum
      level, hyperandrogenemia, together with nutritional status of obesity, might
      contribute to insulin resistance in the pathogenesis of PCOS.

PMID- 23148189
TI  - Noninvasive management of the diabetic foot with critical limb ischemia: current
      options and future perspectives.
AB  - Foot ulcers are a major complication in patients with diabetes mellitus and
      involve dramatic restrictions to quality of life and also lead to enormous socio
      economical loss due to the high amputation rate. The poor and slow wound healing
      is often aggravated by the frequent comorbidity of foot ulcers with peripheral
      arterial disease, making the treatment of this condition even more complicated.
      While the local treatment of foot ulcers is mainly based on mechanical relief and
      prevention or treatment of infection, improving perfusion of the impaired tissue
      remains the major challenge in peripheral arterial disease. While focal arterial
      stenosis is the domain of interventional angioplasty or vascular surgery,
      patients with critical limb ischemia and lacking options for revascularization
      have a much worse prognosis, because current treatment options avoiding
      amputation are scarce. However, based on recent research efforts, there is rising
      hope for promising and more-effective therapeutic approaches for these patients.
      Here, we discuss the current improvements of established therapies aimed at an
      improvement of limb perfusion, as well as the development of novel cutting-edge
      therapies based on stem-cell technology. The experiences of a 'high-volume
      center' for treatment of diabetic foot syndrome with a current major amputation
      rate of 4% are discussed.

PMID- 23148190
TI  - The efficacy of octreotide LAR in acromegalic patients as primary or secondary
      therapy.
AB  - OBJECTIVE: The objective of this study was to investigate the efficacy of
      octreotide therapy in acromegalic patients as primary or secondary therapy.
      METHODS: Ten acromegalic patients diagnosed at the Endocrinology Clinic in
      Sarajevo (seven females and three males, mean age 55.2 +/- 7.2 years, age range
      40-65 years, five patients with microadenoma and five patients with macroadenoma)
      were treated with octreotide. Among them, 60% of patients were operated on and
      the majority of the procedures were performed transnasaly (90%). That group of
      patients had recidivism of disease (pituitary adenoma and acromegaly). The
      concentration of human growth hormone (HGH) and insulin-like growth factor 1 (IGF
      1) was evaluated at 0, 6 and 12 months, while magnetic resonance imaging (MRI)
      was taken before the treatment and 12 months after. Eight patients received
      octreotide 30 mg/28 days, one patient received a dose of 20 mg and the other
      received 60 mg/28 days. RESULTS: Before treatment growth hormone (GH) levels were
      50.87 +/- 10.56 ng/ml (range: 26-64.9), IGF-1 were 776.66 +/- 118.40 ng/ml
      (range: 526-934). Four patients (40%) were treated with primary octreotide
      treatment and six patients (60%) with secondary somatostatin analog treatment. At
      the beginning of therapy, there were no differences in terms of age, HGH levels
      and IGF-1 levels between primary and secondary treatment groups (p > 0.05). The
      difference between groups was only in regard to the size of tumors (p = 0.01).
      After 6 and 12 months the GH levels decreased to 1.61 +/- 0.86 ng/ml (range: 0.7
      2.65) and 1.85 +/- 2.40 ng/ml (range: 0.0-8.3), respectively, while the IGF-1
      became 305.90 +/- 43.19 ng/ml after 6 months of treatment (range: 240-376) and
      256.99 +/- 71.43 ng/ml after 12 months of octreotide treatment (range: 126-325),
      respectively. The pituitary adenomas size prior to treatment was 9.57 mm, while
      after 12 months of treatment, the size decreased to 8.0 mm. After therapy, a GH
      decrease to less than 2.5 ng/ml was achieved in 90% of cases; tumor size decrease
      was achieved in 60% while normalization of IGF-1 was achieved in 100% of the
      patients, respectively. All differences about HGH and IGF-1 in each group were
      statistically significant (p < 0.05). In the group of acromegalic patients
      treated with octreotide LAR as primary therapy, the difference was more
      significant for GH and IGF-1 than for adenomas size. CONCLUSIONS: Octreotide
      treatment of acromegaly not only decreases GH and IGF-1 concentrations, but also
      appears to diminish the size of the tumor in about 60% of cases. The somatostatin
      analogs are more efficient in the primary treatment of acromegalic patients, due
      to the fact that primary therapy is as effective as secondary therapy but primary
      therapy has small advantages when compared with secondary octreotide therapy
      because no surgical treatment is required before.

PMID- 23148193
TI  - New therapeutic efforts and upcoming developments in the field of diabetes
      medicine and endocrinology.

PMID- 23148194
TI  - Efficacy and safety of ultra-long-acting insulin degludec.
AB  - All patients with type 1 diabetes and significant numbers of those with type 2
      diabetes are treated with insulin. Nonadherence to insulin regimen can impact
      glycaemic control. Insulin degludec is a new generation, ultra-long-acting basal
      insulin that forms soluble multihexamers at the injection site that slowly
      release insulin degludec monomers into the circulation giving a prolonged
      duration of action. Insulin degludec may provide a safe and convenient dosing
      option for patients who require some flexibility in adhering to an insulin
      regimen according to their lifestyle or circumstances. In this review we focus on
      the early phases of insulin degludec development.

PMID- 23148191
TI  - Pheochromocytoma - update on disease management.
AB  - Pheochromocytomas are rare endocrine tumors that can present insidiously and
      remain undiagnosed until death or onset of clear manifestations of catecholamine
      excess. They are often referred to as one of the 'great mimics' in medicine.
      These tumors can no longer be regarded as a uniform disease entity, but rather as
      a highly heterogeneous group of chromaffin cell neoplasms with different ages of
      onset, secretory profiles, locations, and potential for malignancy according to
      underlying genetic mutations. These aspects all have to be considered when the
      tumor is encountered, thereby enabling optimal management for the patient.
      Referral to a center of specialized expertise for the disease should be
      considered wherever possible. This is not only important for surgical management
      of patients, but also for post-surgical follow up and screening of disease in
      patients with a hereditary predisposition to the tumor. While preoperative
      management has changed little over the last 20 years, surgical procedures have
      evolved so that laparoscopic resection is the standard of care and partial
      adrenalectomy should be considered in all patients with a hereditary condition.
      Follow-up testing is essential and should be recommended and ensured on a yearly
      basis. Managing such patients must now also take into account possible underlying
      mutations and the appropriate selection of genes for testing according to disease
      presentation. Patients and family members with identified mutations then require
      an individualized approach to management. This includes consideration of distinct
      patterns of biochemical test results during screening and the appropriate choice
      of imaging studies for tumor localization according to the mutation and
      associated differences in predisposition to adrenal, extra-adrenal and metastatic
      disease.

PMID- 23148196
TI  - Autologous derived, platelet-rich plasma gel in the treatment of nonhealing
      diabetic foot ulcer: a case report.

PMID- 23148198
TI  - The clinical pharmacology of obesity.

PMID- 23148199
TI  - Rationale and design of PATRO Adults, a multicentre, noninterventional study of
      the long-term efficacy and safety of Omnitrope((r)) for the treatment of adult
      patients with growth hormone deficiency.
AB  - OBJECTIVE: To describe the rationale and design of PATRO Adults, a postmarketing
      surveillance study of the long-term efficacy and safety of somatropin
      (Omnitrope((r))) for the treatment of adult patients with growth hormone
      deficiency (GHD). METHODS: PATRO Adults is an observational, multicentre, open,
      longitudinal, noninterventional study being conducted in hospitals and
      specialized endocrinology clinics across several European countries. The primary
      objective is to assess the safety and efficacy of Omnitrope((r)) in adults
      treated in routine clinical practice. Eligible patients are male or female adults
      who are receiving treatment with Omnitrope((r)) and who have provided informed
      consent. Patients who have been treated with another human growth hormone (hGH)
      product before starting Omnitrope((r)) therapy will also be eligible for
      inclusion. Efficacy assessments will be based on the analysis of the following:
      insulin-like growth factor-1 levels within age- and gender-adjusted normal
      ranges; anthropometric measures (weight, waist circumference, total fat mass,
      lean body mass, total body water); bone mineral density; lipids; effects on
      cardiovascular risk factors such as glucose metabolism, blood pressure and
      inflammatory markers (e.g. C-reactive protein); and quality of life. All adverse
      events will be monitored and recorded. Particular emphasis will be placed on long
      term safety, the recording of malignancies, the occurrence and clinical impact of
      antirecombinant hGH antibodies, the incidence, severity and duration of
      hyperglycaemia, and the development of diabetes during treatment with
      Omnitrope((r)). CONCLUSIONS: PATRO Adults is a large, long-term, postmarketing
      surveillance study that will extend the safety database for Omnitrope((r)), as
      well as contributing to the available data for all recombinant hGH products. Of
      particular interest, the study will provide important data on the impact of long
      term GH replacement therapy on the development of diabetes mellitus, the
      recurrence/regrowth of hypothalamic-pituitary tumours, and de novo malignancy or
      recurrence of other (non-hypothalamic-pituitary) tumours.

PMID- 23148195
TI  - Clinical management of SIADH.
AB  - Hyponatremia is the most frequent electrolyte disorder and the syndrome of
      inappropriate antidiuretic hormone secretion (SIADH) accounts for approximately
      one-third of all cases. In the diagnosis of SIADH it is important to ascertain
      the euvolemic state of extracellular fluid volume, both clinically and by
      laboratory measurements. SIADH should be treated to cure symptoms. While this is
      undisputed in the presence of grave or advanced symptoms, the clinical role and
      the indications for treatment in the presence of mild to moderate symptoms are
      currently unclear. Therapeutic modalities include nonspecific measures and means
      (fluid restriction, hypertonic saline, urea, demeclocycline), with fluid
      restriction and hypertonic saline commonly used. Recently vasopressin receptor
      antagonists, called vaptans, have been introduced as specific and direct therapy
      of SIADH. Although clinical experience with vaptans is limited at this time, they
      appear advantageous to patients because there is no need for fluid restriction
      and the correction of hyponatremia can be achieved comfortably and within a short
      time. Vaptans also appear to be beneficial for physicians and staff because of
      their efficiency and reliability. The side effects are thirst, polydipsia and
      frequency of urination. In any therapy of chronic SIADH it is important to limit
      the daily increase of serum sodium to less than 8-10 mmol/liter because higher
      correction rates have been associated with osmotic demyelination. In the case of
      vaptan treatment, the first 24 h are critical for prevention of an overly rapid
      correction of hyponatremia and the serum sodium should be measured after 0, 6, 24
      and 48 h of treatment. Discontinuation of any vaptan therapy for longer than 5 or
      6 days should be monitored to prevent hyponatremic relapse. It may be necessary
      to taper the vaptan dose or restrict fluid intake or both.

PMID- 23148192
TI  - The effects of old, new and emerging medicines on metabolic aberrations in PCOS.
AB  - Polycystic ovary syndrome (PCOS) is a common endocrine disorder in women of
      reproductive age that is associated with significant adverse short- and long-term
      health consequences. Multiple metabolic aberrations, such as insulin resistance
      (IR) and hyperinsulinaemia, high incidence of impaired glucose tolerance,
      visceral obesity, inflammation and endothelial dysfunction, hypertension and
      dyslipidemia are associated with the syndrome. Assessing the metabolic
      aberrations and their long term health impact in women with PCOS is challenging
      and becomes more important as therapeutic interventions currently available for
      the management of PCOS are not fully able to deal with all these consequences.
      Current therapeutic management of PCOS has incorporated new treatments resulting
      from the better understanding of the pathophysiology of the syndrome. The aim of
      this review is to summarize the effect of old, new and emerging therapies used in
      the management of PCOS, on the metabolic aberrations of PCOS.

PMID- 23148200
TI  - Antihypertensive treatment in patients with class 3 obesity.
AB  - BACKGROUND: Even though patients with class 3 obesity (body mass index >= 40
      kg/m(2)) are prone to arterial hypertension and respond less to antihypertensive
      drugs, they are not considered in hypertension treatment guidelines and data from
      prospective clinical trials are lacking. METHODS: In a post hoc analysis of a
      clinical trial, we compared patients with class 3 obesity with patients with
      class 1/2 obesity. RESULTS AND CONCLUSIONS: Blood pressure control in class 3
      obesity was less likely to be achieved with hydrochlorothiazide monotherapy.
      While addition of amlodipine, irbesartan, or aliskiren to hydrochlorothiazide
      improved the blood pressure response, amlodipine was less effective and induced
      peripheral edema in 19% of patients with class 3 obesity.

PMID- 23148201
TI  - Efficacy and safety of insulin lispro protamine suspension as basal
      supplementation in patients with type 2 diabetes.
AB  - The three currently marketed long-acting insulin analogs, glargine, detemir and
      insulin lispro protamine suspension (ILPS), represent the most significant
      advances in basal insulin supplementation since the 1940s and 1950s and the
      introduction of the intermediate-acting NPH (neutral protamine Hagedorn) insulin.
      As injection of NPH insulin lacks chronic maintenance of a steady-state low-level
      basal insulin during fasting periods, which can also expose patients to
      unpredictable nocturnal hypoglycemia, long-acting insulin analogs have been
      developed to overcome this important limitation of NPH insulin. ILPS is a
      protamine-based, intermediate-acting insulin formulation of the short-acting
      analog insulin lispro: its pharmacokinetic and pharmacodynamic characteristics
      are quite similar to the other basal insulin analogs glargine and detemir. In
      recent head-to-head randomized controlled trials of insulin-naive patients with
      type 2 diabetes, ILPS achieved similar glycemic control compared with glargine or
      detemir. ILPS administered once daily is an effective and safe way to maintain a
      steady-state low-level basal insulin during night time, not dissimilar from that
      currently obtained with a one-day glargine or detemir administration.

PMID- 23148202
TI  - Elective frozen replacement cycles for all: ready for prime time?
AB  - Conventionally, most in vitro fertilization (IVF) embryos are transferred in
      fresh treatment cycles with freezing reserved for spare ones. Improvement in
      cryopreservation facilities over time has encouraged the greater use of this
      technology with the success rate of frozen replacement cycles approaching that
      associated with fresh embryo transfer. Data from observational studies suggest
      that obstetric and perinatal outcomes are better in pregnancies resulting from
      frozen replacement cycles. In the interests of promoting feto-maternal safety is
      it therefore time to avoid fresh embryo transfers in IVF, freeze all available
      embryos and replace them in subsequent cycles? In this article we explore the
      biological plausibility of this concept, appraise the evidence underpinning it
      and consider the implications of adopting such a strategy in routine clinical
      practice. The outcomes of existing randomized trials appear to favour a strategy
      of frozen embryo transfer, but larger trials are needed before a major change in
      clinical practice can be considered.

PMID- 23148203
TI  - Sequential comprehensive chromosome analysis on polar bodies, blastomeres and
      trophoblast: insights into female meiotic errors and chromosomal segregation in
      the preimplantation window of embryo development.
AB  - STUDY QUESTION: What is the optimal stage from oocyte through preimplantation
      embryo development for biopsy and preimplantation genetic screening (PGS) to
      detect abnormal chromosome segregation patterns in eggs or embryos from advanced
      maternal age (AMA) patients? SUMMARY ANSWER: Testing at the polar body (PB) stage
      was the least accurate mainly due to the high incidence of post-zygotic events.
      This suggests that postponing the time of biopsy to the blastocyst stage of
      preimplantation embryo development may provide the most reliable results for PGS.
      WHAT IS KNOWN ALREADY: In the PGS field there is an ongoing debate about the
      optimal biopsy stage for PGS. This is a result of the lack of understanding of
      how aneuploidy arises in the human embryo. To date, most of the cytogenetic data
      obtained during PGS investigations have been derived through the analysis of
      cells at isolated points in the preimplantation window, thus potentially missing
      critical information on chromosomal segregation. Understanding the chromosome
      segregation patterns during preimplantation development holds the potential to
      significantly increase the success rates of IVF. In this study, a sequential
      comprehensive chromosome analysis of both the PBs and the corresponding embryos
      at both the cleavage and the blastocyst stages is presented. STUDY DESIGN, SIZE,
      DURATION: This is a prospective longitudinal cohort study performed between
      October 2009 and August 2011 involving 9 infertile couples and 21 sets of
      complete comprehensive chromosomal screening data, including PB1, PB2,
      corresponding blastomeres and trophectoderm (TE) samples. PARTICIPANTS/MATERIALS,
      SETTING, METHODS: Infertile couples undergoing IVF cycles with PGS where the
      female partner was older than 40 years and with a good response to controlled
      ovarian stimulation (>10 MII oocytes retrieved) were enrolled into the study. The
      exclusion criteria were (i) patients presenting with abnormal karyotype; (ii)
      specific ovarian pathologies including polycystic ovary syndrome, endometriosis
      grade III or higher and premature ovarian failure and (iii) severe male factor
      infertility (motile sperm count of <500 000/ml after preparation of a fresh
      ejaculate). The PBs, blastomere and TE samples were sequentially biopsied and
      analyzed by array comparative genomic hybridization (aCGH). The analysis of
      chromosome segregation patterns was performed to infer the origin of aneuploidy
      and to investigate the diagnostic accuracy of both PB and cleavage-stage PGS
      strategies. MAIN RESULTS AND THE ROLE OF CHANCE: Twenty-one sets of complete data
      (PB1/PB2/blastomere/TE) including 84 aCGH experiments showed a pattern of
      multiple meiotic errors typically caused by sister chromatid separation errors
      and predominantly arising in the second meiotic division. Twenty-two of the 24
      (91.7%) errors in the first meiotic division arose as a consequence of premature
      sister chromatid predivision. In half of these cases, the second meiotic division
      resulted in a balancing chromosome segregation event producing a normal female
      complement for that chromosome in the resulting embryo. Overall, only 62 out of
      78 (79.5%) of the abnormal meiotic segregations had errors in the either one or
      both PBs consistent with the aneuploidies observed in their resulting embryos.
      Ten of the 21 (47.6%) embryos had aneuploidies other than female meiotic-derived
      ones, most of which detected on Day 3 and confirmed on Day 5 or 6 of embryo
      development (20/25) with chromosomal loss being three times more frequent than
      gains. Notably, as high as 20% of female-derived aneuploidies detected on PBs and
      confirmed on Day 3 were rescued at the blastocyst stage, mainly as a result of
      diploidization of trisomic chromosomes. On a per chromosome basis, the
      sensitivity in predicting blastocyst chromosomal complement was significantly
      lower for PB approach, 61.7%, compared with blastomeres analysis, 86.4% (P <
      0.01). LIMITATIONS, REASONS FOR CAUTION: The study was limited to the analysis of
      oocytes and embryos from AMA patients. Thus, these findings apply only to this
      patient group. Comparisons with other patient populations including patients with
      different indications for PGS should be made in future research. In addition,
      higher resolution and/or more accurate chromosomal screening tests could be used
      in future studies to corroborate the current findings. WIDER IMPLICATIONS OF THE
      FINDINGS: These findings provide critical insights into the mechanisms causing
      errors during female meiosis and the preimplantation embryo development period to
      improve the design and treatment outcome of PGS.

PMID- 23148204
TI  - A national evaluation of antibiotic expenditures by healthcare setting in the
      United States, 2009.
AB  - OBJECTIVES: Promoting appropriate antibiotic use has the potential to decrease
      healthcare costs by reducing unnecessary prescriptions and the incidence of
      resistant infections. However, little is known about where antibiotic costs are
      incurred in the US healthcare system. We evaluated antibiotic expenditures by
      healthcare setting and antibiotic class in the USA. METHODS: Systemic antibiotic
      expenditures in 2009 were extracted from the IMS Health((c)) National Sales
      Perspectives database. These data represent a statistically valid projection of
      all medication purchases in the USA from 1 January 2009 to 31 December 2009.
      RESULTS: Antibiotic expenditures totalled $10.7 billion. The majority (61.5%) of
      expenditures were associated with the outpatient setting, especially from
      community pharmacies. Inpatient and long-term care settings accounted for 33.6%
      and 4.9% of expenditures, respectively. The class of antibiotics that accounted
      for the most antibiotic expenditure overall was the quinolones, followed by the
      penicillins. CONCLUSIONS: Over $10.7 billion was spent in 2009 on antibiotic
      therapy in the USA. Differences were observed in antibiotic expenditures by
      healthcare setting, with the majority in the outpatient setting, 87% of which was
      in community pharmacies.

PMID- 23148205
TI  - Ultrasensitive detection of mRNA extracted from cancerous cells achieved by DNA
      rotaxane-based cross-rolling circle amplification.
AB  - An ultrasensitive and highly selective method for polymerase chain reaction-free
      (PCR-free) messenger RNA (mRNA) expression profiling is developed through a novel
      cross-rolling circle amplification (C-RCA) process based on DNA-rotaxane
      nanostructures. Two species of DNA pseudorotaxane (DPR) superstructures (DPR-I
      and DPR-II) are assembled by threading a linear DNA rod through a double-stranded
      DNA (dsDNA) ring containing two single-stranded gaps. In this assay, cDNA that is
      specific for beta-actin (ACTB) mRNA is taken as a model analyte. Upon the
      introduction of the target cDNA, the cDNA and the biotin-modified primer are
      hybridized to the single-stranded regions of the DNA rod and the gap-ring,
      respectively. As a result, the DPR-I dethreads into free DNA macrocycle and a
      dumbbell-shaped DNA nanostructure. In the presence of DNA polymerase/dNTPs, two
      release-DNA on the DPR-I are replaced by polymerase with strand-displacement
      activity, which can act as the input of the DPR-II to trigger the dethreading of
      DPR-II and the RCA reaction, releasing another two specified release-DNA strands
      those in turn serve as the "mimic cDNA" for DPR-I. The C-RCA reaction then
      proceeds autonomously. To overcome the high background induced by hemin itself,
      the biotinylated rolling circle products are captured by streptavidin-coated
      MNPs, achieving a detection limit as low as 0.1 zmol cDNA. The assay also
      exhibits an excellent selectivity due to its unique DNA nanostructure fabricated
      through base pairing hybridization. The ACTB mRNA expression in mammary cancer
      cells (MCF-7) is successfully detected.

PMID- 23148206
TI  - Lipid-coated nanocapillaries for DNA sensing.
AB  - We report a simple and efficient way to accomplish the chemical modification of
      glass nanopores by means of lipid self-assembly. Lipid coating improves the
      success rate of these glass nanopores as biosensors to detect lambda-DNA.

PMID- 23148207
TI  - Comment on revalidating swallowing assessments.
AB  - PURPOSE: A letter to the editor is presented regarding the recently published
      article by Gonzalez-Fernandez, Sein, and Palmer (2011). In this letter, Dr.
      Giselle Carnaby stipulates that although Gonzalez-Fernandez and colleagues'
      article reports on the revalidation of a common swallowing assessment tool, it
      does not, however, fully address issues surrounding (a) the use of retrospective
      data for revalidation, (b) the impact of missing data on analyses, and (c) the
      failure to replicate an assessment's scoring system. CONCLUSION: These issues are
      pertinent for the readership of the American Journal of Speech-Language Pathology
      (AJSLP) and for the interpretation and development of future assessment tools in
      this area.

PMID- 23148209
TI  - Uncoupling proteostasis and development in vitro with a small molecule inhibitor
      of the pancreatic endoplasmic reticulum kinase, PERK.
AB  - Loss-of-function mutations in EIF2AK3, encoding the pancreatic endoplasmic
      reticulum (ER) kinase, PERK, are associated with dysfunction of the endocrine
      pancreas and diabetes. However, to date it has not been possible to uncouple the
      long term developmental effects of PERK deficiency from sensitization to
      physiological levels of ER unfolded protein stress upon interruption of PERK
      modulation of protein synthesis rates. Here, we report that a selective PERK
      inhibitor acutely deregulates protein synthesis in freshly isolated islets of
      Langerhans, across a range of glucose concentrations. Acute loss of the PERK
      mediated strand of the unfolded protein response leads to rapid accumulation of
      misfolded pro-insulin in cultured beta cells and is associated with a kinetic
      defect in pro-insulin processing. These in vitro observations uncouple the latent
      role of PERK in beta cell development from the regulation of unfolded protein
      flux through the ER and attest to the importance of the latter in beta cell
      proteostasis.

PMID- 23148211
TI  - Protein-disulfide isomerase regulates the thyroid hormone receptor-mediated gene
      expression via redox factor-1 through thiol reduction-oxidation.
AB  - Protein-disulfide isomerase (PDI) is a dithiol/disulfide oxidoreductase that
      regulates the redox state of proteins. We previously found that overexpression of
      PDI in rat pituitary tumor (GH3) cells suppresses 3,3',5-triiodothyronine (T(3))
      stimulated growth hormone (GH) expression, suggesting the contribution of PDI to
      the T(3)-mediated gene expression via thyroid hormone receptor (TR). In the
      present study, we have clarified the mechanism of regulation by which TR function
      is regulated by PDI. Overexpression of wild-type but not redox-inactive mutant
      PDI suppressed the T(3)-induced GH expression, suggesting that the redox activity
      of PDI contributes to the suppression of GH. We considered that PDI regulates the
      redox state of the TR and focused on redox factor-1 (Ref-1) as a mediator of the
      redox regulation of TR by PDI. Interaction between Ref-1 and TRbeta1 was
      detected. Overexpression of wild-type but not C64S Ref-1 facilitated the GH
      expression, suggesting that redox activity of Cys-64 in Ref-1 is involved in the
      TR-mediated gene expression. Moreover, PDI interacted with Ref-1 and changed the
      redox state of Ref-1, suggesting that PDI controls the redox state of Ref-1. Our
      studies suggested that Ref-1 contributes to TR-mediated gene expression and that
      the redox state of Ref-1 is regulated by PDI. Redox regulation of PDI via Ref-1
      is a new aspect of PDI function.

PMID- 23148210
TI  - Hypoxia-inducible factor 1-alpha induces miR-210 in normoxic differentiating
      myoblasts.
AB  - MicroRNA-210 (miR-210) induction is a virtually constant feature of the hypoxic
      response in both normal and transformed cells, regulating several key aspects of
      cardiovascular diseases and cancer. We found that miR-210 was induced in normoxic
      myoblasts upon myogenic differentiation both in vitro and in vivo. miR-210
      transcription was activated in an hypoxia-inducible factor 1-alpha (Hif1a)
      dependent manner, and chromatin immunoprecipitation experiments show that Hif1a
      bound to the miR-210 promoter only in differentiated myotubes. Accordingly,
      luciferase reporter assays demonstrated the functional relevance of the Hif1a
      binding site for miR-210 promoter activation in differentiating myoblasts. To
      investigate the functional relevance of increased miR-210 levels in
      differentiated myofibers, we blocked miR-210 with complementary locked nucleic
      acid oligonucleotides (anti-miR-210). We found that C2C12 myoblast cell line
      differentiation was largely unaffected by anti-miR-210. Likewise, miR-210
      inhibition did not affect skeletal muscle regeneration following cardiotoxin
      damage. However, we found that miR-210 blockade greatly increased myotube
      sensitivity to oxidative stress and mitochondrial dysfunction. In conclusion, miR
      210 is induced in normoxic myofibers, playing a cytoprotective role.

PMID- 23148212
TI  - An ultra-specific avian antibody to phosphorylated tau protein reveals a unique
      mechanism for phosphoepitope recognition.
AB  - Highly specific antibodies to phosphoepitopes are valuable tools to study
      phosphorylation in disease states, but their discovery is largely empirical, and
      the molecular mechanisms mediating phosphospecific binding are poorly understood.
      Here, we report the generation and characterization of extremely specific
      recombinant chicken antibodies to three phosphoepitopes on the Alzheimer disease
      associated protein tau. Each antibody shows full specificity for a single
      phosphopeptide. The chimeric IgG pT231/pS235_1 exhibits a K(D) of 0.35 nm in 1:1
      binding to its cognate phosphopeptide. This IgG is murine ortholog-cross
      reactive, specifically recognizing the pathological form of tau in brain samples
      from Alzheimer patients and a mouse model of tauopathy. To better understand the
      underlying binding mechanisms allowing such remarkable specificity, we determined
      the structure of pT231/pS235_1 Fab in complex with its cognate phosphopeptide at
      1.9 A resolution. The Fab fragment exhibits novel complementarity determining
      region (CDR) structures with a "bowl-like" conformation in CDR-H2 that tightly
      and specifically interacts with the phospho-Thr-231 phosphate group, as well as a
      long, disulfide-constrained CDR-H3 that mediates peptide recognition. This
      binding mechanism differs distinctly from either peptide- or hapten-specific
      antibodies described to date. Surface plasmon resonance analyses showed that
      pT231/pS235_1 binds a truly compound epitope, as neither phosphorylated Ser-235
      nor free peptide shows any measurable binding affinity.

PMID- 23148213
TI  - A Na+/Ca2+ exchanger-like protein (AtNCL) involved in salt stress in Arabidopsis.
AB  - Calcium ions (Ca(2+)) play a crucial role in many key physiological processes;
      thus, the maintenance of Ca(2+) homeostasis is of primary importance.
      Na(+)/Ca(2+) exchangers (NCXs) play an important role in Ca(2+) homeostasis in
      animal excitable cells. Bioinformatic analysis of the Arabidopsis genome
      suggested the existence of a putative NCX gene, Arabidopsis NCX-like (AtNCL),
      encoding a protein with an NCX-like structure and different from Ca(2+)/H(+)
      exchangers and Na(+)/H(+) exchangers previously identified in plant. AtNCL was
      identified to localize in the Arabidopsis cell membrane fraction, have the
      ability of binding Ca(2+), and possess NCX-like activity in a heterologous
      expression system of cultured mammalian CHO-K1 cells. AtNCL is broadly expressed
      in Arabidopsis, and abiotic stresses stimulated its transcript expression. Loss
      of-function atncl mutants were less sensitive to salt stress than wild-type or
      AtNCL transgenic overexpression lines. In addition, the total calcium content in
      whole atncl mutant seedlings was higher than that in wild type by atomic
      absorption spectroscopy. The level of free Ca(2+) in the cytosol and Ca(2+) flux
      at the root tips of atncl mutant plants, as detected using transgenic aequorin
      and a scanning ion-selective electrode, required a longer recovery time following
      NaCl stress compared with that in wild type. All of these data suggest that AtNCL
      encodes a Na(+)/Ca(2+) exchanger-like protein that participates in the
      maintenance of Ca(2+) homeostasis in Arabidopsis. AtNCL may represent a new type
      of Ca(2+) transporter in higher plants.

PMID- 23148214
TI  - Depletion of the ubiquitin-binding adaptor molecule SQSTM1/p62 from macrophages
      harboring cftr DeltaF508 mutation improves the delivery of Burkholderia
      cenocepacia to the autophagic machinery.
AB  - Cystic fibrosis is the most common inherited lethal disease in Caucasians. It is
      caused by mutations in the cystic fibrosis transmembrane conductance regulator
      (CFTR), of which the cftr DeltaF508 mutation is the most common. DeltaF508
      macrophages are intrinsically defective in autophagy because of the sequestration
      of essential autophagy molecules within unprocessed CFTR aggregates. Defective
      autophagy allows Burkholderia cenocepacia (B. cepacia) to survive and replicate
      in DeltaF508 macrophages. Infection by B. cepacia poses a great risk to cystic
      fibrosis patients because it causes accelerated lung inflammation and, in some
      cases, a lethal necrotizing pneumonia. Autophagy is a cell survival mechanism
      whereby an autophagosome engulfs non-functional organelles and delivers them to
      the lysosome for degradation. The ubiquitin binding adaptor protein SQSTM1/p62 is
      required for the delivery of several ubiquitinated cargos to the autophagosome.
      In WT macrophages, p62 depletion and overexpression lead to increased and
      decreased bacterial intracellular survival, respectively. In contrast, depletion
      of p62 in DeltaF508 macrophages results in decreased bacterial survival, whereas
      overexpression of p62 leads to increased B. cepacia intracellular growth.
      Interestingly, the depletion of p62 from DeltaF508 macrophages results in the
      release of the autophagy molecule beclin1 (BECN1) from the mutant CFTR aggregates
      and allows its redistribution and recruitment to the B. cepacia vacuole,
      mediating the acquisition of the autophagy marker LC3 and bacterial clearance via
      autophagy. These data demonstrate that p62 differentially dictates the fate of B.
      cepacia infection in WT and DeltaF508 macrophages.

PMID- 23148216
TI  - AlkB dioxygenase preferentially repairs protonated substrates: specificity
      against exocyclic adducts and molecular mechanism of action.
AB  - Efficient repair by Escherichia coli AlkB dioxygenase of exocyclic DNA adducts
      3,N(4)-ethenocytosine, 1,N(6)-ethenoadenine, 3,N(4)-alpha-hydroxyethanocytosine,
      and reported here for the first time 3,N(4)-alpha-hydroxypropanocytosine requires
      higher Fe(II) concentration than the reference 3-methylcytosine. The pH optimum
      for the repair follows the order of pK(a) values for protonation of the adduct,
      suggesting that positively charged substrates favorably interact with the
      negatively charged carboxylic group of Asp-135 side chain in the enzyme active
      center. This interaction is supported by molecular modeling, indicating that
      1,N(6)-ethenoadenine and 3,N(4)-ethenocytosine are bound to AlkB more favorably
      in their protonated cationic forms. An analysis of the pattern of intermolecular
      interactions that stabilize the location of the ligand points to a role of Asp
      135 in recognition of the adduct in its protonated form. Moreover, ab initio
      calculations also underline the role of substrate protonation in lowering the
      free energy barrier of the transition state of epoxidation of the etheno adducts
      studied. The observed time courses of repair of mixtures of stereoisomers of
      3,N(4)-alpha-hydroxyethanocytosine or 3,N(4)-alpha-hydroxypropanocytosine are
      unequivocally two-exponential curves, indicating that the respective isomers are
      repaired by AlkB with different efficiencies. Molecular modeling of these adducts
      bound by AlkB allowed evaluation of the participation of their possible
      conformational states in the enzymatic reaction.

PMID- 23148215
TI  - Bile acids induce pancreatic acinar cell injury and pancreatitis by activating
      calcineurin.
AB  - Biliary pancreatitis is the leading cause of acute pancreatitis in both children
      and adults. A proposed mechanism is the reflux of bile into the pancreatic duct.
      Bile acid exposure causes pancreatic acinar cell injury through a sustained rise
      in cytosolic Ca(2+). Thus, it would be clinically relevant to know the targets of
      this aberrant Ca(2+) signal. We hypothesized that the Ca(2+)-activated
      phosphatase calcineurin is such a Ca(2+) target. To examine calcineurin
      activation, we infected primary acinar cells from mice with an adenovirus
      expressing the promoter for a downstream calcineurin effector, nuclear factor of
      activated T-cells (NFAT). The bile acid taurolithocholic acid-3-sulfate (TLCS)
      was primarily used to examine bile acid responses. TLCS caused calcineurin
      activation only at concentrations that cause acinar cell injury. The activation
      of calcineurin by TLCS was abolished by chelating intracellular Ca(2+).
      Pretreatment with 1,2-bis(o-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid
      (acetoxymethyl ester) (BAPTA-AM) or the three specific calcineurin inhibitors
      FK506, cyclosporine A, or calcineurin inhibitory peptide prevented bile acid
      induced acinar cell injury as measured by lactate dehydrogenase leakage and
      propidium iodide uptake. The calcineurin inhibitors reduced the intra-acinar
      activation of chymotrypsinogen within 30 min of TLCS administration, and they
      also prevented NF-kappaB activation. In vivo, mice that received FK506 or were
      deficient in the calcineurin isoform Abeta (CnAbeta) subunit had reduced
      pancreatitis severity after infusion of TLCS or taurocholic acid into the
      pancreatic duct. In summary, we demonstrate that acinar cell calcineurin is
      activated in response to Ca(2+) generated by bile acid exposure, bile acid
      induced pancreatic injury is dependent on calcineurin activation, and calcineurin
      inhibitors may provide an adjunctive therapy for biliary pancreatitis.

PMID- 23148217
TI  - Tropomyosin dephosphorylation results in compensated cardiac hypertrophy.
AB  - Phosphorylation of tropomyosin (Tm) has been shown to vary in mouse models of
      cardiac hypertrophy. Little is known about the in vivo role of Tm
      phosphorylation. This study examines the consequences of Tm dephosphorylation in
      the murine heart. Transgenic (TG) mice were generated with cardiac specific
      expression of alpha-Tm with serine 283, the phosphorylation site of Tm, mutated
      to alanine. Echocardiographic analysis and cardiomyocyte cross-sectional area
      measurements show that alpha-Tm S283A TG mice exhibit a hypertrophic phenotype at
      basal levels. Interestingly, there are no alterations in cardiac function,
      myofilament calcium (Ca(2+)) sensitivity, cooperativity, or response to beta
      adrenergic stimulus. Studies of Ca(2+) handling proteins show significant
      increases in sarcoplasmic reticulum ATPase (SERCA2a) protein expression and an
      increase in phospholamban phosphorylation at serine 16, similar to hearts under
      exercise training. Compared with controls, the decrease in phosphorylation of
      alpha-Tm results in greater functional defects in TG animals stressed by
      transaortic constriction to induce pressure overload-hypertrophy. This is the
      first study to investigate the in vivo role of Tm dephosphorylation under both
      normal and cardiac stress conditions, documenting a role for Tm dephosphorylation
      in the maintenance of a compensated or physiological phenotype. Collectively,
      these results suggest that modification of the Tm phosphorylation status in the
      heart, depending upon the cardiac state/condition, may modulate the development
      of cardiac hypertrophy.

PMID- 23148218
TI  - Neuregulin mediates F-actin-driven cell migration through inhibition of protein
      kinase D1 via Rac1 protein.
AB  - Neuregulin (NRG; heregulin) is overexpressed in ~30% of breast cancers and
      mediates various processes involved in tumor progression, including tumor cell
      migration and invasion. Here, we show that NRG mediates its effects on tumor cell
      migration via PKD1. Downstream of RhoA, PKD1 can prevent directed cell migration
      through phosphorylation of its substrate SSH1L. NRG exerts its inhibitory effects
      on PKD1 through Rac1/NADPH oxidase, leading to decreased PKD1 activation loop
      phosphorylation and decreased activity toward SSH1L. The consequence of PKD1
      inhibition by NRG is decreased binding of 14-3-3 to SSH1L, localization of SSH1L
      to F-actin at the leading edge, and increased cofilin activity, resulting in
      increased reorganization of the actin cytoskeleton and cell motility. Our data
      provide a mechanism through which the Rho GTPase Rac1 cross-talks with PKD1
      signaling pathways to facilitate directed cell migration.

PMID- 23148219
TI  - Insertions within the actin core of actin-related protein 3 (Arp3) modulate
      branching nucleation by Arp2/3 complex.
AB  - The Arp2/3 (actin-related protein 2/3) complex nucleates branched actin filaments
      involved in multiple cellular functions, including endocytosis and cellular
      motility. Two subunits (Arp2 and Arp3) in this seven-subunit assembly are closely
      related to actin and upon activation of the complex form a "cryptic dimer" that
      stably mimics an actin dimer to nucleate a new filament. Both Arps contain a
      shared actin core structure, and each Arp contains multiple insertions of unknown
      function at conserved positions within the core. Here we characterize three key
      insertions within the actin core of Arp3 and show that each one plays a distinct
      role in modulating Arp2/3 function. The beta4/beta5 insert mediates interactions
      of Arp2/3 complex with actin filaments and "dampers" the nucleation activity of
      the complex. The Arp3 hydrophobic plug plays an important role in maintaining the
      integrity of the complex but is not absolutely required for formation of the
      daughter filament nucleus. Deletion of the alphaK/beta15 insert did not
      constitutively activate the complex, as previously hypothesized. Instead, it
      abolished in vitro nucleation activity and caused defects in endocytic actin
      patch assembly in fission yeast, indicating a role for the alphaK/beta15 insert
      in the activated state of the complex. Biochemical characterization of each
      mutant revealed steps in the nucleation pathway influenced by each Arp3-specific
      insert to provide new insights into the structural basis of activation of the
      complex.

PMID- 23148221
TI  - Chaperone proteins select and maintain [PIN+] prion conformations in
      Saccharomyces cerevisiae.
AB  - Prions are proteins that can adopt different infectious conformations known as
      "strains" or "variants," each with a distinct, epigenetically inheritable
      phenotype. Mechanisms by which prion variants are determined remain unclear. Here
      we use the Saccharomyces cerevisiae prion Rnq1p/[PIN(+)] as a model to
      investigate the effects of chaperone proteins upon prion variant determination.
      We show that deletion of specific chaperone genes alters [PIN(+)] variant
      phenotypes, including [PSI(+)] induction efficiency, Rnq1p aggregate
      morphology/size and variant dominance. Mating assays demonstrate that gene
      deletion-induced phenotypic changes are stably inherited in a non-Mendelian
      manner even after restoration of the deleted gene, confirming that they are due
      to a bona fide change in the [PIN(+)] variant. Together, our results demonstrate
      a role for chaperones in regulating the prion variant complement of a cell.

PMID- 23148220
TI  - Kinetic characterization of nonmuscle myosin IIb at the single molecule level.
AB  - Nonmuscle myosin IIB (NMIIB) is a cytoplasmic myosin, which plays an important
      role in cell motility by maintaining cortical tension. It forms bipolar thick
      filaments with ~14 myosin molecule dimers on each side of the bare zone. Our
      previous studies showed that the NMIIB is a moderately high duty ratio (~20-25%)
      motor. The ADP release step (~0.35 s(-1)) of NMIIB is only ~3 times faster than
      the rate-limiting phosphate release (0.13 +/- 0.01 s(-1)). The aim of this study
      was to relate the known in vitro kinetic parameters to the results of single
      molecule experiments and to compare the kinetic and mechanical properties of
      single- and double-headed myosin fragments and nonmuscle IIB thick filaments.
      Examination of the kinetics of NMIIB interaction with actin at the single
      molecule level was accomplished using total internal reflection fluorescence
      (TIRF) with fluorescence imaging with 1-nm accuracy (FIONA) and dual-beam optical
      trapping. At a physiological ATP concentration (1 mm), the rate of detachment of
      the single-headed and double-headed molecules was similar (~0.4 s(-1)). Using
      optical tweezers we found that the power stroke sizes of single- and double
      headed heavy meromyosin (HMM) were each ~6 nm. No signs of processive stepping at
      the single molecule level were observed in the case of NMIIB-HMM in optical
      tweezers or TIRF/in vitro motility experiments. In contrast, robust motility of
      individual fluorescently labeled thick filaments of full-length NMIIB was
      observed on actin filaments. Our results are in good agreement with the previous
      steady-state and transient kinetic studies and show that the individual
      nonprocessive nonmuscle myosin IIB molecules form a highly processive unit when
      polymerized into filaments.

PMID- 23148222
TI  - Hsp33 controls elongation factor-Tu stability and allows Escherichia coli growth
      in the absence of the major DnaK and trigger factor chaperones.
AB  - Intracellular de novo protein folding is assisted by cellular networks of
      molecular chaperones. In Escherichia coli, cooperation between the chaperones
      trigger factor (TF) and DnaK is central to this process. Accordingly, the
      simultaneous deletion of both chaperone-encoding genes leads to severe growth and
      protein folding defects. Herein, we took advantage of such defective phenotypes
      to further elucidate the interactions of chaperone networks in vivo. We show that
      disruption of the TF/DnaK chaperone pathway is efficiently rescued by
      overexpression of the redox-regulated chaperone Hsp33. Consistent with this
      observation, the deletion of hslO, the Hsp33 structural gene, is no longer
      tolerated in the absence of the TF/DnaK pathway. However, in contrast with other
      chaperones like GroEL or SecB, suppression by Hsp33 was not attributed to its
      potential overlapping general chaperone function(s). Instead, we show that
      overexpressed Hsp33 specifically binds to elongation factor-Tu (EF-Tu) and
      targets it for degradation by the protease Lon. This synergistic action of Hsp33
      and Lon was responsible for the rescue of bacterial growth in the absence of TF
      and DnaK, by presumably restoring the coupling between translation and the
      downstream folding capacity of the cell. In support of this hypothesis, we show
      that overexpression of the stress-responsive toxin HipA, which inhibits EF-Tu,
      also rescues bacterial growth and protein folding in the absence of TF and DnaK.
      The relevance for such a convergence of networks of chaperones and proteases
      acting directly on EF-Tu to modulate the intracellular rate of protein synthesis
      in response to protein aggregation is discussed.

PMID- 23148223
TI  - Crystal structure of reduced MsAcg, a putative nitroreductase from Mycobacterium
      smegmatis and a close homologue of Mycobacterium tuberculosis Acg.
AB  - This paper presents the structure of MsAcg (MSMEG_5246), a Mycobacterium
      smegmatis homologue of Mycobacterium tuberculosis Acg (Rv2032) in its reduced
      form at 1.6 A resolution using x-ray crystallography. Rv2032 is one of the most
      induced genes under the hypoxic model of tuberculosis dormancy. The Acg family
      turns out to be unusual flavin mononucleotide (FMN)-binding proteins that have
      probably arisen by gene duplication and fusion from a classical homodimeric
      nitroreductase such that the monomeric protein resembles a classical
      nitroreductase dimer but with one active site deleted and the other active site
      covered by a unique lid. The FMN cofactor is not reduced by either NADH or NADPH,
      but the chemically reduced enzyme is capable of reduction of nitro substrates,
      albeit at no kinetic advantage over free FMN. The reduced enzyme is rapidly
      oxidized by oxygen but without any evidence for a radical state commonly seen in
      oxygen-sensitive nitroreductases. The presence of the unique lid domain, the lack
      of reduction by NAD(P)H, and the slow rate of reaction of the chemically reduced
      protein raises a possible alternative function of Acg proteins in FMN storage or
      sequestration from other biochemical pathways as part of the bacteria's
      adaptation to a dormancy state.

PMID- 23148224
TI  - High mobility group Box 1 inhibits human pulmonary artery endothelial cell
      migration via a Toll-like receptor 4- and interferon response factor 3-dependent
      mechanism(s).
AB  - In pulmonary hypertension the loss of precapillary arterioles results from
      vascular injury causing endothelial dysfunction. Endothelial cell migration and
      proliferation are critical for vascular regeneration. This study focused on the
      effect of high mobility group box 1 protein (HMGB1) on these critical processes.
      HMGB1 had no effect on human pulmonary artery endothelial cell (HPAEC)
      proliferation. In contrast, treatment of HPAECs with HMGB1 dose-dependently
      inhibited VEGF-stimulated HPAEC migration. The effect of HMGB1 on HPAEC migration
      was TLR4-dependent because it was reversed by TLR4 siRNA or TLR4-neutralizing
      antibody. Exposure of HPAECs to hypoxia caused translocation and release of HMGB1
      and inhibition of HPAEC migration. The effect of hypoxia on HPAEC migration was
      mediated by HMGB1 because HMGB1-neutralizing antibody but not control IgG
      restored HPAEC migration. Likewise, TLR4 siRNA but not control siRNA reversed the
      inhibitory effect of hypoxia in HPAECs. The canonical TLR4 signaling pathway
      requires the adaptor protein MyD88 and leads to downstream NFkappaB activation.
      Interestingly, HMGB1 failed to stimulate NFkappaB translocation to the nucleus,
      but instead activated an alternative pathway characterized by activation of
      interferon response factor 3 (IRF3). This was in contrast to human umbilical vein
      endothelial cells in which HMGB1 stimulated nuclear translocation of NFkappaB but
      not IRF3. IRF3 siRNA, but not MyD88 siRNA, reversed the inhibitory effect of
      HMGB1 on HPAEC migration. These data demonstrate that HMGB1 inhibits HPAEC
      migration, a critical process for vascular regeneration, via TLR4- and IRF3
      dependent mechanisms.

PMID- 23148225
TI  - Tumor necrosis factor receptor-associated factor 6 (TRAF6) and TGFbeta-activated
      kinase 1 (TAK1) play essential roles in the C-type lectin receptor signaling in
      response to Candida albicans infection.
AB  - Tumor necrosis factor receptor-associated factor 6 (TRAF6) and TGFbeta-activated
      kinase 1 (TAK1) are considered as key intermediates in Toll-like receptor (TLR)
      signaling. However, the role of TRAF6 and TAK1 in C-type lectin receptors (CLRs)
      in response to fungal infection has not been studied. In this study, we have
      utilized macrophages derived from TRAF6 knock-out mice and myeloid-specific TAK1
      deficient mice and determined the role of TRAF6 and TAK1 in CLR-induced signal
      transduction events. We demonstrate that TRAF6 and TAK1 are required for NF
      kappaB and JNK activation, and expression of proinflammatory cytokines in
      response to Candida albicans infection. Our results highlight TRAF6 and TAK1 as
      key components in the signaling cascade downstream of C-type lectin receptors and
      as critical mediators of the anti-fungal immune response. Therefore, our studies
      provide a mechanistic understanding of the host immune response to C. albicans,
      which has a significant impact for the development of anti-fungal therapeutics
      and in understanding risk-factors and determining susceptibility to C. albicans
      infection.

PMID- 23148226
TI  - Heparin oligosaccharides inhibit chemokine (CXC motif) ligand 12 (CXCL12)
      cardioprotection by binding orthogonal to the dimerization interface, promoting
      oligomerization, and competing with the chemokine (CXC motif) receptor 4 (CXCR4)
      N terminus.
AB  - The ability to interact with cell surface glycosaminoglycans (GAGs) is essential
      to the cell migration properties of chemokines, but association with soluble GAGs
      induces the oligomerization of most chemokines including CXCL12. Monomeric
      CXCL12, but not dimeric CXCL12, is cardioprotective in a number of experimental
      models of cardiac ischemia. We found that co-administration of heparin, a common
      treatment for myocardial infarction, abrogated the protective effect of CXCL12 in
      an ex vivo rat heart model for myocardial infarction. The interaction between
      CXCL12 and heparin oligosaccharides has previously been analyzed through
      mutagenesis, in vitro binding assays, and molecular modeling. However,
      complications from heparin-induced CXCL12 oligomerization and studies using very
      short oligosaccharides have led to inconsistent conclusions as to the residues
      involved, the orientation of the binding site, and whether it overlaps with the
      CXCR4 N-terminal site. We used a constitutively dimeric variant to simplify the
      NMR analysis of CXCL12-binding heparin oligosaccharides of varying length.
      Biophysical and mutagenic analyses reveal a CXCL12/heparin interaction surface
      that lies perpendicular to the dimer interface, does not involve the chemokine N
      terminus, and partially overlaps with the CXCR4-binding site. We further
      demonstrate that heparin-mediated enzymatic protection results from the promotion
      of dimerization rather than direct heparin binding to the CXCL12 N terminus.
      These results clarify the structural basis for GAG recognition by CXCL12 and lend
      insight into the development of CXCL12-based therapeutics.

PMID- 23148227
TI  - Runt-related transcription factor 1 (RUNX1) stimulates tumor suppressor p53
      protein in response to DNA damage through complex formation and acetylation.
AB  - Representative tumor suppressor p53 plays a critical role in the regulation of
      proper DNA damage response. In this study, we have found for the first time that
      Runt-related transcription factor 1 (RUNX1) contributes to p53-dependent DNA
      damage response. Upon adriamycin (ADR) exposure, p53 as well as RUNX1 were
      strongly induced in p53-proficient HCT116 and U2OS cells, which were closely
      associated with significant transactivation of p53 target genes, such as
      p21(WAF)(1), BAX, NOXA, and PUMA. RUNX1 was exclusively expressed in the cell
      nucleus and formed a complex with p53 in response to ADR. Chromatin
      immunoprecipitation assay demonstrated that p53 together with RUNX1 are
      efficiently recruited onto p53 target gene promoters following ADR exposure,
      indicating that RUNX1 is involved in p53-mediated transcriptional regulation.
      Indeed, forced expression of RUNX1 stimulated the transcriptional activity of p53
      in response to ADR. Consistent with these observations, knockdown of RUNX1
      attenuated ADR-mediated induction of p53 target genes and suppressed ADR
      dependent apoptosis. Furthermore, RUNX1 was associated with p300 histone
      acetyltransferase, and ADR-dependent acetylation of p53 at Lys-373/382 was
      markedly inhibited in RUNX1 knockdown cells. In addition, knockdown of RUNX1
      resulted in a significant decrease in the amount of p53-p300 complex following
      ADR exposure. Taken together, our present results strongly suggest that RUNX1 is
      required for the stimulation of p53 in response to DNA damage and also provide
      novel insight into understanding the molecular mechanisms behind p53-dependent
      DNA damage response.

PMID- 23148229
TI  - Gaudenz Danuser: the symphony of the cell. Interview by Caitlin Sedwick.

PMID- 23148228
TI  - Re-evaluation of the role of calcium homeostasis endoplasmic reticulum protein
      (CHERP) in cellular calcium signaling.
AB  - Changes in cytoplasmic Ca(2+) concentration, resulting from activation of
      intracellular Ca(2+) channels within the endoplasmic reticulum, regulate several
      aspects of cellular growth and differentiation. Ca(2+) homeostasis endoplasmic
      reticulum protein (CHERP) is a ubiquitously expressed protein that has been
      proposed as a regulator of both major families of endoplasmic reticulum Ca(2+)
      channels, inositol 1,4,5-trisphosphate receptors (IP(3)Rs) and ryanodine
      receptors (RyRs), with resulting effects on mitotic cycling. However, the manner
      by which CHERP regulates intracellular Ca(2+) channels to impact cellular growth
      is unknown. Here, we challenge previous findings that CHERP acts as a direct
      cytoplasmic regulator of IP(3)Rs and RyRs and propose that CHERP acts in the
      nucleus to impact cellular proliferation by regulating the function of the U2
      snRNA spliceosomal complex. The previously reported effects of CHERP on cellular
      growth therefore are likely indirect effects of altered spliceosomal function,
      consistent with prior data showing that loss of function of U2 snRNP components
      can interfere with cell growth and induce cell cycle arrest.

PMID- 23148230
TI  - Cell biology: a key driver of therapeutic innovation.
AB  - All processes associated with cellular function are likely to contribute to
      disease. Particularly in the cancer field, most major therapeutic innovations
      have originated from the elucidation of basic molecular mechanisms by academic
      researchers. Recent breakthroughs in molecularly targeted drug discovery have
      made it clear that it is the depth with which a biological process is understood
      that empowers its translation. We propose that early, more strategic, support of
      cutting-edge academic research by industry may be more effective for
      translational purposes than the current model of a late selection of community
      evolved projects.

PMID- 23148231
TI  - New frontiers in human cell biology and medicine: can pluripotent stem cells
      deliver?
AB  - Human pluripotent stem cells provide enormous opportunities to treat disease
      using cell therapy. But human stem cells can also drive biomedical and cell
      biological discoveries in a human model system, which can be directly linked to
      understanding disease or developing new therapies. Finally, rigorous scientific
      studies of these cells can and should inform the many science and medical policy
      issues that confront the translation of these technologies to medicine. In this
      paper, I discuss these issues using amyotrophic lateral sclerosis as an example.

PMID- 23148232
TI  - Development of proteasome inhibitors as research tools and cancer drugs.
AB  - The proteasome is the primary site for protein degradation in mammalian cells,
      and proteasome inhibitors have been invaluable tools in clarifying its cellular
      functions. The anticancer agent bortezomib inhibits the major peptidase sites in
      the proteasome's 20S core particle. It is a "blockbuster drug" that has led to
      dramatic improvements in the treatment of multiple myeloma, a cancer of plasma
      cells. The development of proteasome inhibitors illustrates the unpredictability,
      frustrations, and potential rewards of drug development but also emphasizes the
      dependence of medical advances on basic biological research.

PMID- 23148233
TI  - A novel motif in the yeast mitochondrial dynamin Dnm1 is essential for adaptor
      binding and membrane recruitment.
AB  - To initiate mitochondrial fission, dynamin-related proteins (DRPs) must bind
      specific adaptors on the outer mitochondrial membrane. The structural features
      underlying this interaction are poorly understood. Using yeast as a model, we
      show that the Insert B domain of the Dnm1 guanosine triphosphatase (a DRP)
      contains a novel motif required for association with the mitochondrial adaptor
      Mdv1. Mutation of this conserved motif specifically disrupted Dnm1-Mdv1
      interactions, blocking Dnm1 recruitment and mitochondrial fission. Suppressor
      mutations in Mdv1 that restored Dnm1-Mdv1 interactions and fission identified
      potential protein-binding interfaces on the Mdv1 beta-propeller domain. These
      results define the first known function for Insert B in DRP-adaptor interactions.
      Based on the variability of Insert B sequences and adaptor proteins, we propose
      that Insert B domains and mitochondrial adaptors have coevolved to meet the
      unique requirements for mitochondrial fission of different organisms.

PMID- 23148234
TI  - A flagellar A-kinase anchoring protein with two amphipathic helices forms a
      structural scaffold in the radial spoke complex.
AB  - A-kinase anchoring proteins (AKAPs) contain an amphipathic helix (AH) that binds
      the dimerization and docking (D/D) domain, RIIa, in cAMP-dependent protein kinase
      A (PKA). Many AKAPs were discovered solely based on the AH-RIIa interaction in
      vitro. An RIIa or a similar Dpy-30 domain is also present in numerous diverged
      molecules that are implicated in critical processes as diverse as flagellar
      beating, membrane trafficking, histone methylation, and stem cell
      differentiation, yet these molecules remain poorly characterized. Here we
      demonstrate that an AKAP, RSP3, forms a dimeric structural scaffold in the
      flagellar radial spoke complex, anchoring through two distinct AHs, the RIIa and
      Dpy-30 domains, in four non-PKA spoke proteins involved in the assembly and
      modulation of the complex. Interestingly, one AH can bind both RIIa and Dpy-30
      domains in vitro. Thus, AHs and D/D domains constitute a versatile yet
      potentially promiscuous system for localizing various effector mechanisms. These
      results greatly expand the current concept about anchoring mechanisms and AKAPs.

PMID- 23148235
TI  - Cdc42 promotes transendothelial migration of cancer cells through beta1 integrin.
AB  - Cancer cells interact with endothelial cells during the process of metastatic
      spreading. Here, we use a small interfering RNA screen targeting Rho GTPases in
      cancer cells to identify Cdc42 as a critical regulator of cancer cell-endothelial
      cell interactions and transendothelial migration. We find that Cdc42 regulates
      beta1 integrin expression at the transcriptional level via the transcription
      factor serum response factor (SRF). beta1 integrin is the main target for Cdc42
      mediating interaction of cancer cells with endothelial cells and the underlying
      extracellular matrix, as exogenous beta1 integrin expression was sufficient to
      rescue the Cdc42-silencing phenotype. We show that Cdc42 was required in vivo for
      cancer cell spreading and protrusion extension along blood vessels and retention
      in the lungs. Interestingly, transient Cdc42 depletion was sufficient to decrease
      experimental lung metastases, which suggests that its role in endothelial
      attachment is important for metastasis. By identifying beta1 integrin as a
      transcriptional target of Cdc42, our results provide new insight into Cdc42
      function.

PMID- 23148236
TI  - Nucleoside salvage pathway kinases regulate hematopoiesis by linking nucleotide
      metabolism with replication stress.
AB  - Nucleotide deficiency causes replication stress (RS) and DNA damage in dividing
      cells. How nucleotide metabolism is regulated in vivo to prevent these
      deleterious effects remains unknown. In this study, we investigate a functional
      link between nucleotide deficiency, RS, and the nucleoside salvage pathway (NSP)
      enzymes deoxycytidine kinase (dCK) and thymidine kinase (TK1). We show that
      inactivation of dCK in mice depletes deoxycytidine triphosphate (dCTP) pools and
      induces RS, early S-phase arrest, and DNA damage in erythroid, B lymphoid, and T
      lymphoid lineages. TK1(-/-) erythroid and B lymphoid lineages also experience
      nucleotide deficiency but, unlike their dCK(-/-) counterparts, they still sustain
      DNA replication. Intriguingly, dCTP pool depletion, RS, and hematopoietic defects
      induced by dCK inactivation are almost completely reversed in a newly generated
      dCK/TK1 double-knockout (DKO) mouse model. Using NSP-deficient DKO hematopoietic
      cells, we identify a previously unrecognized biological activity of endogenous
      thymidine as a strong inducer of RS in vivo through TK1-mediated dCTP pool
      depletion. We propose a model that explains how TK1 and dCK "tune" dCTP pools to
      both trigger and resolve RS in vivo. This new model may be exploited
      therapeutically to induce synthetic sickness/lethality in hematological
      malignancies, and possibly in other cancers.

PMID- 23148238
TI  - Growth and Development Symposium: Development, characterization, and use of a
      porcine epiblast-derived liver stem cell line: ARS-PICM-19.
AB  - Totipotent embryonic stem cell lines have not been established from ungulates;
      however, we have developed a somatic stem cell line from the in vitro culture of
      pig epiblast cells. The cell line, ARS-PICM-19, was isolated via colony cloning
      and was found to spontaneously differentiate into hepatic parenchymal epithelial
      cell types, namely hepatocytes and bile duct cells. Hepatocytes form as
      monolayers and bile duct cells as 3-dimensional bile ductules. Transmission
      electron microscopy revealed that the ductules were composed of radially
      arranged, monociliated cells with their cilia projecting into the lumen of the
      ductule whereas hepatocytes were arranged in monolayers with lateral canalicular
      structures containing numerous microvilli and connected by tight junctions and
      desmosomes. Extensive Golgi and rough endoplasmic reticulum networks were also
      present, indicative of active protein synthesis. Analysis of conditioned medium
      by 2-dimensional electrophoresis and mass spectrometry indicated a spectrum of
      serum-protein secretion by the hepatocytes. The PICM-19 cell line maintains a
      range of inducible cytochrome P450 activities and, most notably, is the only
      nontransformed cell line that synthesizes urea in response to ammonia challenge.
      The PICM-19 cell line has been used for several biomedical- and agricultural
      related purposes, such as the in vitro replication of hepatitis E virus, a
      zoonotic virus of pigs, and a spaceflight experiment to evaluate somatic stem
      cell differentiation and liver cell function in microgravity. The cell line was
      also evaluated as a platform for toxicity testing and has been used in a
      commercial artificial liver rescue device bioreactor. A PICM-19 subclone, PICM
      19H, which only differentiates into hepatocytes, was isolated and methods are
      currently under development to grow PICM-19 cells without feeder cells. Feeder
      cell-independent growth will facilitate the study of mesenchymal-parenchymal
      interactions that influence the divergent differentiation of the PICM-19 cells,
      enhance our ability to genetically modify the cells, and provide a better model
      system to investigate porcine hepatic metabolism.

PMID- 23148239
TI  - Comparison of some aspects of the in situ and in vitro methods in evaluation of
      neutral detergent fiber digestion.
AB  - The objective of the present study was to compare digestion rates (kd) of NDF for
      different feeds estimated with the in situ method or derived from an automated
      gas in vitro system. A meta-analysis was conducted to evaluate how in situ
      derived kd of NDF related to in vivo digestibility of NDF. Furthermore, in vitro
      true digestibility of the feed samples incubated within filter bags or dispersed
      in the medium was compared, and kd for insoluble and soluble components of those
      feeds were estimated. Four different concentrates and 4 forages were used in this
      study. Two lactating Swedish Red cows fed a diet of 60% grass silage and 40%
      concentrate on DM basis were used for in situ incubations and for collection of
      rumen fluid. The feed samples were ground through a 2.0-mm screen before the in
      situ incubations and a 1.0-mm screen before the in vitro gas incubations. In situ
      nylon bags were introduced into the rumen for determination of kd of NDF.
      Additional kinetic data were produced from isolated NDF and intact samples
      subjected to in vitro incubations in which gas production was recorded for 72 h.
      Samples were weighed in the bottles or within filter bags (for fiber and in vitro
      studies) that were placed in the bottles. The interaction between feed and method
      was significant (P < 0.01); kd of NDF for grass hay tended (P = 0.06) to be less
      whereas kd of NDF for alfalfa, barley grain, canola meal, and dried sugar beet
      pulp were greater (P < 0.01) when estimated with the in situ method than from gas
      production recordings. The meta-analysis suggested that in situ derived kd of NDF
      were biased and underestimated in vivo digestibility of NDF. Digestion rates of
      the intact samples were lower for all feeds, except for the hay, when incubated
      within the bags compared with dispersed in the medium (P < 0.01). Less OM and NDF
      were digested for all feeds when incubated within bags than dispersed in the
      medium (P < 0.01). It is concluded from the in vitro study that microbial
      activity within the bags is less than in the medium. Significant interactions
      between method (in situ vs. in vitro) and feed suggest that one or both methods
      result in biased estimates of digestion kinetics.

PMID- 23148237
TI  - A novel role of sphingosine 1-phosphate receptor S1pr1 in mouse thrombopoiesis.
AB  - Millions of platelets are produced each hour by bone marrow (BM) megakaryocytes
      (MKs). MKs extend transendothelial proplatelet (PP) extensions into BM sinusoids
      and shed new platelets into the blood. The mechanisms that control platelet
      generation remain incompletely understood. Using conditional mutants and
      intravital multiphoton microscopy, we show here that the lipid mediator
      sphingosine 1-phosphate (S1P) serves as a critical directional cue guiding the
      elongation of megakaryocytic PP extensions from the interstitium into BM
      sinusoids and triggering the subsequent shedding of PPs into the blood.
      Correspondingly, mice lacking the S1P receptor S1pr1 develop severe
      thrombocytopenia caused by both formation of aberrant extravascular PPs and
      defective intravascular PP shedding. In contrast, activation of S1pr1 signaling
      leads to the prompt release of new platelets into the circulating blood.
      Collectively, our findings uncover a novel function of the S1P-S1pr1 axis as
      master regulator of efficient thrombopoiesis and might raise new therapeutic
      options for patients with thrombocytopenia.

PMID- 23148240
TI  - Cell Biology Symposium: feed efficiency: mitochondrial function to global gene
      expression.
AB  - Understanding the cellular basis of feed efficiency (FE) is instrumental to
      helping poultry and livestock industries continue to provide high-quality protein
      for an increasingly crowded world. To understand relationships of FE and gene
      expression, global RNA transcription was investigated in breast muscle obtained
      from a male broiler line fed the same diet and individually phenotyped for FE. In
      these studies, RNA samples obtained from broilers that exhibited either high FE
      (0.65 +/- 0.01) or low FE (0.46 +/- 0.01) were analyzed with an Agilent 44K
      chicken oligoarray. A 1.3-fold cutoff in expression (30% difference between
      groups) resulted in 782 genes that were differentially expressed (P < 0.05) in
      muscle between the high- and low-FE phenotypes. Ingenuity Pathway Analysis, an
      online software program, was used to identify genes, gene networks, and pathways
      associated with the phenotypic expression of FE. The results indicate that the
      high-FE phenotype exhibited increased expression of genes associated with 1)
      signal transduction pathways, 2) anabolic activities, and 3) energy-sensing and
      energy coordination activities, all of which would likely be favorable to cell
      growth and development. In contrast, the low-FE broiler phenotype exhibited
      upregulation of genes 1) associated with actin-myosin filaments, cytoskeletal
      architecture, and muscle fibers and 2) stress-related or stress-responsive genes.
      Because the low-FE broiler phenotype exhibits greater oxidative stress, it would
      appear that the low-FE phenotype is the product of inherent gene expression that
      is modulated by oxidative stress. The results of these studies begin to provide a
      comprehensive picture of gene expression in muscle, a major organ of energy
      demand in an animal, associated with phenotypic expression of FE.

PMID- 23148241
TI  - Effect of maternal activity during gestation on maternal behavior, fetal growth,
      umbilical blood flow, and farrowing characteristics in pigs.
AB  - Yorkshire gilts either remained in their individual stall from d 40 to term (CON;
      n = 7) or were subjected to exercise for 30 min 3 times per week from mid to late
      gestation (EX; n = 7) to determine the impact of increased maternal activity
      during gestation on maternal behavior, fetal growth, umbilical blood flow, and
      parturition. In parity 1, maternal body composition (10th rib back fat and LM
      area), maternal behavior, and farrowing characteristics were recorded. In
      parities 1 and 2, fetal growth, fetal heart rate, pulsatility index and
      resistance index, and umbilical blood flow were monitored beginning at d 39 of
      gestation continuing to d 81 of gestation. Exercise continued until d 104. Gilts
      allowed to exercise sat less (P < 0.01), stood more (P < 0.01), tended (P = 0.06)
      to lie down less, and had fewer postural changes (P < 0.01) compared with CON
      gilts. Umbilical blood flow increased (P < 0.01) in EX compared with CON gilts.
      Moreover, gilts had greater (P < 0.01) umbilical blood flow in their first parity
      compared with their second. Indices of vascular resistance were not affected (P
      >= 0.15) by maternal treatment; however, EX gilts reached peak pulsatility index
      earlier than CON gilts (56.2 vs. 64.3 +/- 3.6 d). Fetal weights, piglet birth
      weights, placental weight, interval between piglet births, and blood lactate of
      newborn piglets were unaffected (P >= 0.15) by maternal treatment. Although
      maternal exercise during gestation in the pig increased umbilical blood flow and
      appeared to reduce maternal restlessness, impacts on offspring development in
      postnatal life are not known.

PMID- 23148242
TI  - Effect of corn dried distillers grains with solubles, conjugated linoleic acid,
      and ractopamine (paylean) on growth performance and fat characteristics of late
      finishing pigs.
AB  - An experiment was performed to evaluate effects of dietary ractopamine, CLA, and
      corn distillers dried grains with solubles (DDGS) on growth and carcass and fat
      quality of finishing pigs. This study was conducted as a split-split plot
      arrangement in a generalized randomized block design. In total 1,102 crossbred
      barrows and gilts (initial BW = 100.4 kg, SD = 3.7 kg; pic 337 * c22) were
      randomly assigned to 1 of 8 dietary treatments that consisted of 2 diet sources
      [corn-soybean meal (corn-soy) and corn-soy + 20% DDGS], 2 levels of ractopamine
      (0 and 7.4 mg/kg), and 2 levels of CLA (0% and 0.6%). The pen was the
      experimental unit, with 6 replications per treatment for a total of 48 pens with
      23 pigs per pen. Pigs had ad libitum access to water and feed during the 27-d
      experimental period. Ractopamine addition improved (p < 0.05) ADG and G:F over
      the control group. Furthermore, carcass weight, carcass yield, loin depth, and
      lean percentage were increased and back fat depth was decreased (p < 0.05) by
      feeding ractopamine. Feeding CLA resulted in improved (p < 0.05) ADG and G:F and
      increased lean percentage but reduced carcass yield (p < 0.05). The inclusion of
      DDGS did not affect ADG, adfi, or g:f but reduced (p < 0.05) carcass dressing
      percent. An increase (p < 0.05) in the concentration of pufa was observed with
      inclusion of DDGS, ractopamine, and CLA. Iodine value (iv) increased (p < 0.001)
      in both belly and jowl samples by feeding DDGS and ractopamine, whereas a
      decrease (p < 0.01) was observed when CLA was included in the diets. The fatty
      acid profiles of belly and jowl fat samples were affected (p < 0.05) by diet
      source * ractopamine, indicating that effects of dietary ractopamine depend on
      the fatty acid profile of the diet. These results indicate that feeding
      ractopamine and CLA could improve growth and carcass measures and that CLA was
      effective in diminishing some of the negative effects, especially on IV, caused
      by DDGS.

PMID- 23148243
TI  - Effects of increasing concentrations of glycerol in concentrate diets on nutrient
      digestibility, methane emissions, growth, fatty acid profiles, and carcass traits
      of lambs.
AB  - Two experiments were conducted to evaluate the effects of increasing
      concentrations of glycerol in concentrate diets on total tract digestibility,
      methane (CH4) emissions, growth, fatty acid profiles, and carcass traits of
      lambs. In both experiments, the control diet contained 57% barley grain, 14.5%
      wheat dried distillers grain with solubles (WDDGS), 13% sunflower hulls, 6.5%
      beet pulp, 6.3% alfalfa, and 3% mineral-vitamin mix. Increasing concentrations
      (7, 14, and 21% dietary DM) of glycerol in the dietary DM were replaced for
      barley grain. As glycerol was added, alfalfa meal and WDDGS were increased to
      maintain similar concentrations of CP and NDF among diets. In Exp.1, nutrient
      digestibility and CH4 emissions from 12 ram lambs were measured in a replicated 4
      * 4 Latin square experiment. In Exp. 2, lamb performance was evaluated in 60
      weaned lambs that were blocked by BW and randomly assigned to 1 of the 4 dietary
      treatments and fed to slaughter weight. In Exp. 1, nutrient digestibility and CH4
      emissions were not altered (P = 0.15) by inclusion of glycerol in the diets. In
      Exp.2, increasing glycerol in the diet linearly decreased DMI (P < 0.01) and
      tended (P = 0.06) to reduce ADG, resulting in a linearly decreased final BW. Feed
      efficiency was not affected by glycerol inclusion in the diets. Carcass traits
      and total SFA or total MUFA proportions of subcutaneous fat were not affected (P
      = 0.77) by inclusion of glycerol, but PUFA were linearly decreased (P < 0.01).
      Proportions of 16:0, 10t-18:1, linoleic acid (18:2 n-6) and the n-6/n-3 ratio
      were linearly reduced (P < 0.01) and those of 18:0 (stearic acid), 9c-18:1 (oleic
      acid), linearly increased (P < 0.01) by glycerol. When included up to 21% of diet
      DM, glycerol did not affect nutrient digestibility or CH4 emissions of lambs fed
      barley based finishing diets. Glycerol may improve backfat fatty acid profiles by
      increasing 18:0 and 9c-18:1 and reducing 10t-18:1 and the n-6/n-3 ratio.

PMID- 23148245
TI  - Southern Section Interdisciplinary Beef Cattle Symposium: Forage and co-product
      systems for stockers in the South: have fundamental shifts in markets changed the
      optimal system?
AB  - Stockering calves in the southern United States has been an economically viable
      enterprise for decades. Historically, the system that yielded the best
      opportunity for profitability was to purchase lightweight calves (130 kg to 220
      kg) in autumn, add 100 to 200 kg of BW gain, and sell them in the spring. In most
      years, the value of the BW gain was worth more than the cost of BW gain in this
      system. With the exponential price increases in feed, fuel, and fertilizer during
      2008 and the significant increase in cattle prices, it is prudent to assess the
      potential for continued profitability in this segment of the beef industry.
      Evaluation of 37 grazing experiments indicated that the forage systems most
      likely to result in inexpensive costs of BW gain for stocker calves involve tall
      fescue with legumes or ryegrass with small grains. Even with increased input
      prices, these systems still yield economical BW gain for stocker calves.
      Likewise, many diets can be blended to produce ADG of 1 kg using co-products that
      are abundant across the South. With many of these co-products, the most important
      performance factor in determining their value is G:F. In several experiments, DMI
      has exceeded 3% of BW in stocker calves, and the resulting G:F has been less than
      desirable. Several experiments have reported G:F of 0.13 to 0.16, resulting in
      economical BW gain, whereas some experiments have reported G:F as low as 0.09,
      which could result in BW gain that costs more to produce than it is worth. From
      1979, the value of BW gain for stocker calves in Alabama has averaged US$1.05/kg.
      However, in the last 3 yr, the value of BW gain has risen to $2.32/kg.
      Fundamental shifts in feed, fuel, and fertilizer prices experienced in the United
      States between 2005 and 2010 have markedly changed the amount of capital needed
      to purchase several hundred stocker calves and to provide adequate feedstuffs for
      BW gain. However, the value of BW gain associated with producing feeder calves
      from those stockers has experienced a concomitant increase. The optimal system
      still uses high-quality cool-season forages and supplementation with co-product
      feeds. With this system, a significant margin of profit still exists for the
      Southeastern stocker cattle production system.

PMID- 23148244
TI  - Effects of increasing concentrations of wet distillers grains with solubles in
      steam-flaked, corn-based diets on energy metabolism, carbon-nitrogen balance, and
      methane emissions of cattle.
AB  - The use of wet distillers grains with solubles (WDGS) in feedlot diets has
      increased in the Southern Great Plains as a result of the growing ethanol
      industry. Nutrient balance and respiration calorimetry research evaluating the
      use of steam-flaked corn (SFC)-based diets in conjunction with WDGS is limited.
      Therefore, the effects of increasing concentrations of WDGS in a SFC-based diet
      on energy metabolism, C, and N balance, and enteric methane (CH4) production was
      evaluated in Jersey steers fed at 2 times maintenance, using respiration
      calorimetry chambers. Four treatments were used in two 4 * 4 Latin square
      designs, using 8 steers. Treatments consisted of: 1) SFC-based diet with 0% WDGS
      (SFC-0); 2) SFC-based diet with 15% WDGS (SFC-15); 3) SFC-based diet with 30%
      WDGS (SFC-30); and 4) SFC-based diet with 45% WDGS (SFC-45). Diets were balanced
      for degradable intake protein (DIP) by adding cottonseed meal to the SFC-0 diet.
      As a proportion of GE, fecal, urinary, and CH4 energy increased linearly (P <
      0.03) as WDGS concentration increased in the diet. In contrast, DE, ME, and
      retained energy decreased linearly (P < 0.01) as a proportion of GE as WDGS
      concentration increased. Increasing concentration of WDGS in the diet did not
      affect (P > 0.78) heat production as a proportion of GE. As a result of greater N
      intake, total N excretion increased linearly (P < 0.01) with increasing WDGS
      inclusion in the diet. Fecal C loss and CH4-C respired increased linearly (P <
      0.01) when WDGS concentration increased in the diet whereas CO2-C respired
      decreased (linear, P = 0.05) as WDGS concentration increased. We conclude that
      CH4 production as a proportion of GE increases linearly (P < 0.01) when WDGS
      concentration in the diet is increased; however, dietary inclusion of WDGS at up
      to 45% seems to have no effect (P > 0.78) on heat production as a proportion of
      GE. The reason for a linear decrease in retained energy as WDGS increased was
      likely because of increased fecal energy loss associated with feeding WDGS. Total
      N excretion, fecal C loss, and CH4-C respired increased linearly with increasing
      concentration of WDGS in the diet. We determined NEg values for WDGS to be 2.02,
      1.61, and 1.38 Mcal/kg when included at 15%, 30%, and 45%, respectively, in a SFC
      based diet. From these results we conclude that the energy value (NEg) of WDGS in
      a finishing cattle diet based on SFC must be decreased as the inclusion
      increases.

PMID- 23148246
TI  - Impact of feeding and post prandial time on plasma ketone bodies in sows during
      transition and lactation.
AB  - Two experiments were conducted with the aim of studying how dietary fat source,
      reproductive stage (Exp. 1), and diurnal variation (Exp. 2) affect plasma ketone
      bodies in sows. In Exp. 1, 40 second-parity sows were fed 1 of 5 lactation diets
      from 7 d prepartum until 28 d postpartum, with low or high levels (3% or 8%) of
      dietary fats with different proportions of medium- and long-chain fatty acids.
      Blood was obtained by jugular venipuncture on d 3 and 7 prepartum, and d 1, 10,
      17, and 28 postpartum, and concentrations of plasma beta-hydroxy butyric acid
      (BHBA), acetoacetate + acetone (AcAc+Ac), glucose, NEFA, lactate, acetate, and
      butyrate were determined. For 4 out of 5 treatments, plasma BHBA decreased
      slightly, whereas plasma AcAc+Ac remained stable. However, plasma BHBA (P < 0.01)
      and AcAc+Ac (P < 0.001) doubled after d 10 of lactation in sows fed 4% octanoic
      acid and 4% fish oil diet (4+4% FO; P < 0.001), compared with earlier in
      lactation (P < 0.001). Plasma AcAc+Ac was positively related to BHBA (P < 0.01),
      glucose (P < 0.05), and butyrate (P < 0.001), and negatively related to the
      acetate:butyrate ratio (P < 0.001). In addition, plasma BHBA was positively
      related to lactate (P < 0.01), acetate, and butyrate (P < 0.05). In Exp. 2,
      diurnal variations of plasma metabolites were studied in 5 sows sampled every
      second hour from a jugular catheter throughout a 24-h period on d 5 and 17 of
      lactation and analyzed as in Exp. 1. In addition, milk and urine samples were
      collected and analyzed for BHBA and AcAc+Ac. No diurnal variations in plasma BHBA
      or AcAc+Ac were observed and plasma AcAc+Ac was unchanged from d 5 to 17 of
      lactation (3.7 MUM), whereas BHBA declined from 58 MUM on d 5 of lactation to 52
      MUM on d 17 of lactation (P < 0.05). Minor amounts of AcAc+Ac were found in urine
      (8.6 MUM) and this was not affected by days in milk, whereas the content of
      AcAc+Ac in milk and BHBA in milk and urine were less than the detection limit in
      4 of 5 sows. In conclusion, dietary fat source affected plasma concentrations of
      ketone bodies, but the concentrations were much less than normally observed in
      dairy cows and, therefore, primary ketosis does not appear to be a major problem
      in sows. In addition, this study indicates that the intermediary metabolism of
      sows was challenged when sows were exposed to high fat diets in late gestation.

PMID- 23148247
TI  - Effect of dietary copper and breed on gene products involved in copper
      acquisition, distribution, and use in Angus and Simmental cows and fetuses.
AB  - Copper (Cu) deficiency is a widespread problem in cattle across the United States
      and breed differences in Cu metabolism may contribute to this issue.
      Intracellular Cu is tightly regulated by transport and chaperone proteins, and to
      date, these mechanisms have not been elucidated to address breed differences in
      Cu metabolism, nor have these proteins been characterized in bovine fetal liver.
      Mature, pregnant Angus (n = 8) and Simmental (n = 8) cows (~4 mo into gestation)
      were used in a 2 * 2 factorial arrangement of treatments. All cows were bred to
      Angus sires resulting in an Angus vs. Simmental * Angus comparison for fetuses.
      Cows were randomly assigned to corn silage-based diets that were either adequate
      (+Cu) or deficient (-Cu; 6.6 mg Cu/kg DM) in Cu. Diets were individually fed for
      112 d. At the end of the study, cows were harvested to collect duodenal mucosa
      scrapes, liver samples, and fetal liver samples for mineral analysis and also for
      mRNA and protein analysis of Cu transport and chaperone proteins. Placentomes
      were also obtained for mineral analysis. Plasma Cu and liver Cu were affected by
      Cu, breed, and Cu * breed. Both of these Cu indices were less (P <= 0.05) in-Cu
      Simmentals (-CuS) than in-Cu Angus (- uA), but were similar among +Cu Simmental
      (+CuS) and +Cu Angus cows (+CuA). Duodenal Cu was less (P = 0.01) in-Cu vs. +Cu
      cows. Placentome Cu was less (P = 0.003) in-Cu vs. +Cu cows, and was also less (P
      = 0.03) in Simmentals vs. Angus. Fetal liver Cu was less (P = 0.002) in-Cu vs.
      +Cu fetuses, and was also less (P = 0.05) in Simmental * Angus vs. Angus.
      Abundance of Cu transporter1 (CTR1) protein and transcripts for Cu transporters
      and chaperones were not affected by Cu or breed in liver and were not affected by
      Cu in the intestine. Duodenal Ctr1 was less (P = 0.04) and CTR1 tended (P = 0.10)
      to be less in Simmentals vs. Angus. Expression of Atp7a tended (P = 0.08) to be
      less in Simmentals than in Angus. In fetal liver, expression of antioxidant 1
      (Atox1), cytochrome c oxidase assembly protein 17 (Cox17), and Cu metabolism
      MURR1 domain 1 (Commd1) were up-regulated (P <= 0.05) in-Cu vs. +Cu fetuses. In
      conclusion, less expression of duodenal Ctr1 and a tendency for less CTR1 (P =
      0.10) and Atp7a (P = 0.08) suggest that Simmentals have a lesser ability to
      absorb and utilize dietary Cu, and may explain why Simmentals are more prone to
      Cu deficiency than Angus. Up-regulation of fetal liver Atox1, Cox17, and Commd1
      in-Cu fetuses may reflect the great Cu demand by the fetus.

PMID- 23148248
TI  - Pregnancy establishment and maintenance in cattle.
AB  - A single ovulation, reciprocal embryo transfer study was used to investigate
      effects of oocyte competence and maternal environment on pregnancy establishment
      and maintenance in beef cows. Estrous cycles were synchronized in suckled beef
      cows and embryo donors were inseminated on d 0 (n = 810). Cows were classified on
      d 0 as having a small (<12.5 mm) or large (>=12.5 mm) ovulatory follicle and
      randomly chosen as donors or recipients to remove confounding effects of
      ovulatory follicle size on fertility. Embryos (n = 393) or oocytes (n = 44) were
      recovered on d 7, and all viable embryos were transferred into recipients (n =
      354). All statistical analyses were conducted using the GLM procedure of SAS.
      Path analysis (with significance set at P < 0.10) was used to examine potential
      cause-effect relationships among the measured variables. Greater donor cow BW,
      circulating estradiol concentration at insemination, postpartum interval, and
      ovulatory follicle size directly increased (P < 0.10) fertilization success.
      Greater donor cow age was the only factor that directly decreased (P < 0.10)
      fertilization success. Viability of d-7 embryos was directly inhibited (P < 0.10)
      by rapid follicular growth rate from d -2 to 0 and heavier BW. Direct beneficial
      effects to embryo viability were increased serum progesterone concentration on d 
      2 and ovulatory follicle size. Pregnancy maintenance from d 7 to 27 was enhanced
      (P < 0.10) by increased serum estradiol concentration on d 0 and progesterone
      concentration on d 7 in the recipient cow. Increased follicular diameter in the
      recipient cow on d 0 was detrimental to pregnancy maintenance from d 7 to 27.
      This manuscript defines the complex interplay and relative contributions of
      endocrine and physical factors both prior and subsequent to fertilization that
      influence both oocyte competence and maternal environment and their roles in
      establishment and maintenance of pregnancy.

PMID- 23148249
TI  - Production of reactive oxygen species, gene expression, and enzymatic activity in
      quail subjected to acute heat stress.
AB  - The aim of the present study was to evaluate the effect of acute heat stress on
      the production of mitochondrial reactive oxygen species (ROS), the gene
      expression of the avian uncoupling protein (avUCP) and glutathione peroxidase
      (GPX 7), and the activity of the enzyme GPX in the liver of meat quail. Two
      groups of 15 meat quail (Coturnix coturnix japonica) that were 23 d of age were
      initially housed individually in metallic cages. A period of 7 d was provided for
      the 2 bird groups to adapt to the cages and to a thermoneutral environment at 25
      degrees C with 60% relative humidity. At 30 d of age, 15 quail were exposed to a
      heat stress (HS) treatment of 34 degrees C for 24 h, humidity 60%, whereas
      control quail (n = 15) were kept at 25 degrees C. To analyze the production of
      ROS, 4 quail from each treatment group were slaughtered, and their livers were
      collected for mitochondrial isolation and to measure the subsequent production of
      ROS by the mitochondria. Additionally, the livers of 6 animals from each
      treatment group were collected for total RNA extraction. The cDNA was amplified
      using primers specific for the target genes, and expression was analyzed using
      the real-time PCR reaction (qRT-PCR). Five animals from each treatment group were
      slaughtered to analyze glutathione peroxidase (GPx) activity, which was
      determined by using of hydrogen peroxide (H2O2), and based on measuring the
      amount nicotinamide adenine dinucleotide phosphate oxidized. A greater amount of
      mitochondrial ROS was found in HS animals (0.34 vs. 0.22 nm of ROS produced min(
      1) . mg(-1) of protein, P < 0.05) for the reactions that contained only rotenone
      and in the reactions that were performed with rotenone and antimycin (0.31 vs.
      0.23 nm of ROS produced min(-1) . mg(-1) of protein, P < 0.05). Concomitantly,
      the birds that were subjected to acute heat stress and had a greater amount of
      ROS production expressed less avUCP mRNA [0.75 arbitrary units (AU) vs. 0.87 AU,
      P < 0.05] and more GPX 7 mRNA (2.37 AU vs. 1.17 AU, P < 0.01). The HS quail
      displayed significantly greater GPx activity in their hepatocytes (47.8 vs. 39.6
      nmol of NADPH oxidized per mg of protein per minute, P < 0.05). Thus, acute heat
      stress at 34 degrees C for 24 h affects the production of mitochondrial ROS, the
      expression of avUCP and GPX 7 mRNA, and the activity of the GPx enzyme in the
      liver of meat quail.

PMID- 23148250
TI  - Effectiveness of USDA instrument-based marbling measurements for categorizing
      beef carcasses according to differences in longissimus muscle sensory attributes.
AB  - This study quantified relationships between USDA instrument marbling measurements
      and LM sensory attributes (tenderness, flavor, juiciness), and shear force.
      Heifer (n = 390) and steer (n = 328) carcasses (all A-maturity) were selected at
      4 beef processing plants in Colorado, Kansas, Nebraska, and Texas to represent 7
      marbling degrees: traces (TR), slight (SL), small (SM), modest (MT), moderate
      (MD), slightly abundant (SA), and moderately abundant (MA). Classification into
      marbling groups was based on marbling scores determined using USDA-approved VBG
      2000 grading systems. Strip loin steaks were obtained from both sides of each
      carcass and aged for 14 d. One steak was used to obtain Warner-Bratzler shear
      force (WBSF) and slice shear force (SSF) measurements. The other steak was
      evaluated by a trained sensory panel for juiciness, tenderness, intensity of
      flavors characterized as meaty/brothy, buttery/beef fat, bloody/serumy,
      livery/organy, and grassy; and overall sensory experience (negative or positive).
      Instrument marbling score explained 45%, 40%, 32%, 71%, and 61% of the observed
      variation in panel ratings for juiciness, tenderness, meaty/brothy flavor
      intensity, buttery/beef fat flavor intensity, and overall sensory experience,
      respectively. Increased degree of marbling resulted in steaks having greater (P <
      0.001) juiciness (MA > SA > MD > MT > SM > SL = TR), meaty/brothy flavor (MA = SA
      > MD = MT > SM > SL > TR), and buttery/beef fat flavor (MA > SA > MD > MT > SM >
      SL > TR). Steak tenderness also increased (P < 0.001) as marbling degree
      increased; however, tenderness differences among marbling degrees differed for
      steers (MA = SA > MD = MT > SM > SL = TR) and heifers (MA = SA > MD > MT > SM >
      SL > TR). Steaks produced by steers had lower (P < 0.05) WBSF and SSF values, and
      were rated as more tender by sensory panelists than steaks produced by heifers,
      but the effect of sex on panel tenderness was significant only among steaks with
      TR marbling. Results of this study showed that instrument-based classification of
      beef carcasses, according to differences in marbling, effectively identified
      subsequent differences in strip loin steak sensory performance. Nearly all (98 to
      99%) steaks with MA or SA marbling, and most (between 80% and 90%) steaks with MD
      and MT marbling, received positive ratings for overall sensory experience. In
      comparison, 62% of SM steaks, 29% of SL steaks, and 15% of TR steaks received
      positive sensory experience ratings.

PMID- 23148251
TI  - In growing pigs, the true ileal and total tract digestibility of acid hydrolyzed
      ether extract in extracted corn oil is greater than in intact sources of corn oil
      or soybean oil.
AB  - An experiment was conducted to determine the true ileal digestibility (TID) and
      the true total tract digestibility (TTTD) of acid-hydrolyzed ether extract (AEE)
      in extracted corn oil, high-oil corn, distillers dried grains with solubles
      (DDGS), corn germ, and high protein distillers dried grains (HP DDG) and to
      compare these values to the TID and TTTD of AEE in full-fat soybeans. Nineteen
      barrows with an initial BW of 52.2 kg (SD = 3.8) were fitted with a T-cannula in
      the distal ileum and allotted to a 19 * 11 Youden square design with 19 diets and
      11 periods. A basal diet based on cornstarch, casein, sucrose, and corn bran was
      formulated. Eighteen additional diets were formulated by adding 3 levels of
      extracted corn oil, high-oil corn, DDGS, corn germ, HP DDG, or full-fat soybeans
      to the basal diet. The apparent ileal and the apparent total tract digestibility
      of AEE were calculated for each diet. The endogenous flow of AEE associated with
      each ingredient and values for TID and TTTD were calculated using the regression
      procedure. Results indicated that digested AEE in ileal digesta and feces
      linearly increased as AEE intake increased regardless of ingredient (P < 0.001)
      and the regression of ileal and fecal AEE output against AEE intake was
      significant for all ingredients (P < 0.001; r(2) > 0.77). However, the ileal and
      fecal endogenous losses of AEE were different (P < 0.05) from 0 only for
      extracted corn oil, HP DDG, and full-fat soybeans. The TID of AEE was greater (P
      < 0.05) for extracted corn oil (95.4%) than for all other ingredients. The TID of
      AEE in HP DDG (76.5%) was not different from the TID of AEE in full-fat soybeans
      (85.2%) but greater (P < 0.05) than high-oil corn, DDGS, and corn germ (53.0,
      62.1, and 50.1%, respectively). The TTTD of AEE was greater (P < 0.05) for
      extracted corn oil (94.3%) than for all other ingredients, and the TTTD in full
      fat soybeans (79.7%) was greater (P < 0.05) than the TTTD of AEE in high-oil
      corn, DDGS, corn germ, and HP DDG (41.4, 51.9, 43.9, and 70.2%, respectively).
      The TTTD of AEE in HP DDG was also greater (P < 0.05) than in high-oil corn,
      DDGS, and corn germ. In conclusion, the intact sources of oil originating from
      high-oil corn, DDGS, corn germ, or HP DDG are much less digestible than extracted
      corn oil, and with the exception of HP DDG, these sources of corn oil are also
      less digestible than the intact oil in full fat soybeans.

PMID- 23148252
TI  - Heritability and Bayesian genome-wide association study of first service
      conception and pregnancy in Brangus heifers.
AB  - Brangus [3/8 Brahman (Bos indicus) * 5/8 Angus (Bos taurus); n ~ 800] heifers
      from 67 sires were used to estimate heritability and conduct a genome-wide
      association study (GWAS) for 2 binary fertility traits: first service conception
      (FSC) and heifer pregnancy (HPG). Genotypes were from 53,692 loci on the
      BovineSNP50 (Infinium Bead Chips, Illumina, San Diego, CA). Yearling heifers were
      estrous synchronized, bred by AI, and then exposed to natural service breeding.
      Reproductive ultrasound and DNA-based parentage testing were used to determine if
      the heifer conceived by AI or natural service, and code for FSC and HPG traits.
      Success rates for FSC and HPG were 53.3% and 78.0% +/- 0.01%, and corresponding
      heritability estimates were 0.18 +/- 0.07 and 0.10 +/- 0.06, respectively. The
      models used in obtaining these heritability estimates and GWAS included fixed
      effects of year (i.e., 2005 to 2007), birth location, calving season, age of dam,
      and contemporary group. In GWAS, simultaneous associations of 1 Mb SNP windows
      with phenotype were undertaken with Bayes C analyses using GenSel software. The 1
      Mb windows contained 21.3 +/- 1.1 SNP. Analyses fitted a mixture model that
      treated SNP effects as random, with an assumed fraction pi = 0.9995 having no
      effect on phenotype. The windows that accounted for 1.0% of genetic variance were
      considered as QTL associated with FSC or HPG. Eighteen QTL existed on 15
      chromosomes for the 2 traits. On average, each QTL accounted for 2.43% +/- 0.2%
      of the genetic variance. Chromosome 8 harbored 2 QTL for FSC and 1 for HPG;
      however, these regions did not overlap. Chromosomes 3, 15, 16, 19, 24, 26, 27,
      29, and X included QTL only for FSC, whereas chromosomes 2, 4, 10, 13, and 20
      contained QTL only for HPG. The multitude of QTL detected for FSC and HPG in this
      GWAS involving Brangus heifers exemplifies the complex regulation of variation in
      heifer fertility traits of low heritability.

PMID- 23148253
TI  - In vivo determination of rumen undegradable protein of dried distillers grains
      with solubles and evaluation of duodenal microbial crude protein flow.
AB  - The objectives of this trial were to determine the rumen undegradable protein
      (RUP) of dried distillers grains with solubles (DDGS), to compare the estimates
      of duodenal bacterial CP (BCP) flow using diaminopumelic acid (DAPA) or DNA as
      bacterial markers, and to estimate duodenal protozoal CP (PCP) and yeast CP (YCP)
      flow when DDGS are fed. Three crossbred steers fitted with ruminal and double L
      shaped duodenal cannulae (average BW 780 +/- 137 kg) were used in a 3 treatment,
      6 period crossover design. Animals were housed in individual free stalls and fed
      twice daily at 0700 and 1900 h. Diets (DM basis) were 1) CONTROL, which is 0%
      DDGS but with 19.5% corn bran, 20% sorghum silage, 60% brome hay, 0.5% trace
      minerals, and 0.25% urea, 2) LOW DDGS, which is inclusion of 9.75% DDGS replacing
      equal percentage of corn bran, and 3) HIGH DDGS, which is inclusion of 19.5% DDGS
      completely replacing corn bran. Duodenal BCP flow was estimated using DAPA and
      DNA as bacterial markers. In addition, duodenal PCP and YCP flow were estimated
      using DNA markers. The value of DDGS RUP as a percent of CP was determined to be
      63.0 +/- 0.64%. Estimates of duodenal BCP flow using DAPA were 473, 393, and 357
      +/- 78 g/d (P = 0.09) for CONTROL, LOW DDGS, and HIGH DDGS, respectively.
      Estimates of duodenal BCP flow using DNA were 479, 397, and 368 +/- 74 g/d (P =
      0.14), respectively. Average BCP flow across treatments was unaffected (P = 0.71)
      by marker type and were 404 and 417 +/- 83 g/d for DAPA and DNA markers,
      respectively. Estimates of duodenal PCP flow were 82, 80, and 78 +/- 12 g/d (P =
      0.64) for CONTROL, LOW DDGS, and HIGH DDGS, respectively. Estimates of duodenal
      YCP flow were 0.15, 1.94, and 4.80 +/- 0.66 g/d (P < 0.01) for CONTROL, LOW DDGS,
      and HIGH DDGS, respectively. Duodenal BCP flow tended to decrease with DDGS
      inclusion, but estimates were not affected by marker type. In addition, DDGS did
      not affect duodenal PCP supply and provided small amounts of duodenal YCP.
      Overall, the value of DDGS RUP determined in this study will contribute to a
      better understanding of the effect of this coproduct in ruminant nutrition.

PMID- 23148254
TI  - Meta-analysis of the effects of ractopamine hydrochloride on carcass cutability
      and primal yields of finishing pigs.
AB  - The objective was to summarize previous literature, using a meta-analysis
      approach, on the effects of ractopamine hydrochloride (RAC) when fed at doses of
      5 to 10 mg/kg for up to 35 d before harvest on carcass cutability and belly
      quality of finishing pigs. The meta-analysis provided an opportunity to determine
      the consensus of previously published literature. Ten studies were evaluated to
      determine cutting yields and 8 studies were used to determine belly quality in
      this review. Pooled dietary RAC concentrations (5 mg/kg, 7.4 mg/kg, 10 mg/kg, and
      step-up feeding programs) and pooled feeding durations (up to 35 d before
      harvest) were compared with pigs not fed RAC (controls) and were analyzed as a
      meta-analysis using the mixed procedure of SAS. Ractopamine inclusion was the
      fixed effect in the model and the individual study was considered a random
      variable. The only difference between RAC and control pigs for whole primals as a
      percentage of side weight was the whole ham (P < 0.01). No other differences were
      detected for whole primals as a percentage of side weight. Yet, differences were
      detected in the standardized trimmed primal yields. A difference (P < 0.05) in
      percentages of the side weight was detected for the Boston butt, trimmed loin,
      and trimmed ham. This translated into RAC pigs having a carcass cutting yield
      (74.70% vs. 73.69%, respectively; P = 0.02; SED = 0.33) advantage of 1.01% units
      and a bone in lean cutting yield (61.43% vs. 60.33%, respectively; P = 0.03; SED
      = 0.40) advantage of 1.10% units when compared with control pigs. The advantage
      in bone-in cutability was a result of increased boneless sub primal yields in
      each of the lean cuts (shoulder, loin, and ham). When further evaluated, RAC pigs
      had a boneless shoulder (Boston butt + picnic) yield advantage of 0.32% units (P
      < 0.01; SED = 0.11), a 0.43% unit (P = 0.01; SED = 0.13) yield advantage in the
      boneless loin (Canadian back + tenderloin + sirloin), and a 0.51% unit (P <
      0.001; SED = 0.11) advantage in the boneless ham (inside + outside + knuckle). A
      boneless yield was calculated using a summation of the percentage of side weight
      from the boneless shoulder, boneless loin, and boneless ham, which resulted in a
      1.08% unit (36.28% vs. 35.20%, respectively; P = 0.002; SED = 0.25) advantage of
      RAC pigs when compared with control pigs. There were no subprimal yield
      differences (P = 0.93) in the trimmed belly between RAC pigs (12.18%) and control
      pigs (12.18%). However, RAC pigs (15.27 cm; 73.42) had narrower flop distances (P
      = 0.02; SED = 0.62) and greater iodine values (P = 0.01; SED = 0.33),
      respectively, when compared with control pigs (17.08 cm; 71.48).

PMID- 23148255
TI  - Growth performance, diet nutrient digestibility, and bone mineralization in
      weaned pigs fed pelleted diets containing thermostable phytase.
AB  - Traditional supplemental dietary phytase loses activity during steam pelleting.
      The thermal tolerance and bioefficacy of a phytase product with a
      thermoprotective coating [coated phytase (C-phytase)] was compared in mash and
      pelleted diets to a traditional, uncoated phytase (U-phytase) added to a negative
      control (NC) diet, formulated with reduced dietary Ca and P, and compared with a
      corn-soybean meal based positive control (POC) diet. Growth performance, nutrient
      digestibility, and third metacarpal bone characteristics were response variables.
      Weaned pigs (n = 56; 8.20 +/- 0.5 kg initial BW; 28 d of age) were individually
      housed and randomly allotted to 1 of 7 diets for 21 d. The diets were 1) POC
      mash, 2) NC mash, 3) NC pelleted at 90 degrees C, 4) NC mash + 500 U/kg U
      phytase, 5) NC mash + 500 U/kg C-phytase, 6) NC + 500 U/kg C-phytase pelleted at
      80 degrees C, and 7) NC + 500 U/kg C-phytase pelleted at 90 degrees C. The POC
      and NC diets were formulated to be isoenergetic and isolysinic. The content of Ca
      and available P was 1.01 and 0.40% and 0.83 and 0.22% in the POC and NC diets,
      respectively. Pig BW and feed intake were measured on d 7, 14, and 21, and feces
      were collected for 2 d. On d 21, pigs were killed and ileal digesta and the third
      metacarpal bone collected. Pigs fed POC had greater (P < 0.05) ADG, G:F, P
      digestibility, and bone mineralization but lower (P < 0.01) energy digestibility
      than pigs fed NC. Pelleting the NC diet did not improve performance, nutrient
      digestibility, or P use. Adding the U-phytase to NC mash diet increased (P <
      0.05) ADG, G:F, apparent ileal digestibility (AID) of CP and Ile, Leu, Phe, Thr,
      Val, and Ser, and apparent total tract digestibility (ATTD) of P compared with
      pigs fed NC. Pigs fed C-phytase in NC mash diets had increased (P < 0.05) G:F and
      an AID of CP and AA and ATTD of P compared with pigs fed NC but not different
      than pigs fed U-phytase NC mash diets. Pigs fed pelleted NC diet with C-phytase
      had a greater (P < 0.05) ATTD of P and energy than pigs fed mash NC diet with C
      phytase but had similar growth performance, AID of CP and AA, and bone
      mineralization to pigs fed U-phytase. In conclusion, release and bioefficacy of
      phytase after pelleting was not affected by the thermal protective coating.

PMID- 23148256
TI  - Effects of different polyunsaturated fatty acid supplementations during the
      postpartum periods of early lactating dairy cows on milk yield, metabolic
      responses, and reproductive performances.
AB  - In spite of the difficulties in delivering PUFA to ruminants, studies have
      generally indicated that the PUFA of the omega-6 (linoleic acid) and omega-3
      [alpha-linolenic acid; eicosapentaenoic (EPA), C20:5 omega-3; docosahexaenoic
      (DHA), C22:6 omega-3] families are the most beneficial to improving reproduction
      in cows. The objectives were to determine if a diet enriched in alpha-linolenic
      acid (omega-3) or linoleic acid (omega-6) would influence milk production and
      composition, metabolic status, and reproductive performance in lactating dairy
      cows. High-yielding multiparous Holstein dairy cows (n = 120) with no overt
      clinical illnesses were blocked according to calving date and parity. Cows were
      assigned randomly to be fed 1) soybean whole roast (Soy, omega-6, n = 40) or 2)
      linseed (Lin, omega-3, n = 40) or 3) palm oil as a source of SFA (PO, n = 40)
      from calving until first heat after 40 d postpartum (dpp), and then half of the
      cows in each treatment group were switched to receive either Lin or SFA (PO) from
      first heat after d 40 to 120 dpp. Blood was collected from a subsample of cows.
      Blood was collected at 14 d intervals for 12 wk, starting on the day of calving.
      Results showed milk yield and DMI were not affected. Milk compositions were
      similar (P > 0.08) among diets, except concentration and yield of milk fat
      percentage, which was less in cows fed Lin (P < 0.05). Uterine involution in cows
      fed Soy occurred earlier (P < 0.05). Diets affected day to first estrus and day
      to first insemination in cows (P < 0.05). There were no differences among
      treatments for percent heat detection, percent pregnancy per first insemination,
      and percent conception per AI at estrus. Also, there is a trend of pregnancy by
      120 d, which is 66.7% for the Lin group vs. 50.91% for the PO group (P < 0.08).
      Of the 4 pregnancy losses, 2 occurred in PO-PO group and 2 occurred in Soy-PO
      group, and none occurred in the other 4 treatments. In conclusion, our study
      showed feeding omega-6 fatty acids during 40 dpp could be a good treatment for
      early postpartum periods, and a shift to omega-3 fatty acids until 40 d after AI
      can be considered as a strategy for improving fertility in lactating dairy cows.

PMID- 23148257
TI  - Simulated selection responses for breeding programs including resistance and
      resilience to parasites in Creole goats.
AB  - The Creole goat is a local breed used for meat production in Guadeloupe (French
      West Indies). As in other tropical countries, improvement of parasite resistance
      is needed. In this study, we compared predicted selection responses for
      alternative breeding programs with or without parasite resistance and resilience
      traits. The overall breeding goal included traits for production, reproduction,
      and parasite resilience and resistance to ensure a balanced selection outcome.
      The production traits were BW and dressing percentage (DP). The reproduction
      trait was fertility (FER), which was the number of doe kiddings per mating. The
      resistance trait was worm fecal egg count (FEC), which is a measurement of the
      number of gastro-intestinal parasite eggs found in the feces. The resilience
      trait was the packed cell volume (PCV), which is a measurement of the volume of
      red blood cells in the blood. Dressing percentage, BW, and FEC were measured at
      11 mo of age, which is the mating or selling age. Fertility and PCV were measured
      on females at each kidding period. The breeding program accounting for the
      overall breeding goal and a selection index including all traits gave annual
      selection responses of 800 g for BW, 3.75% for FER, 0.08% for DP, -0.005
      ln(eggs/g) for FEC, and 0.28% for PCV. The expected selection responses for BW
      and DP in this breeding program were reduced by 2% and 6%, respectively, compared
      with a breeding program not accounting for FEC and PCV. The overall breeding
      program, proposed for the Creole breed, offers the best breeding strategy in
      terms of expected selection responses, making it possible to improve all traits
      together. It offers a good balance between production and adaptation traits and
      may present some interest for the selection of other goat breeds in the tropics.

PMID- 23148258
TI  - Selection for genetic markers in beef cattle reveals complex associations of
      thyroglobulin and casein1-s1 with carcass and meat traits.
AB  - Genetic markers in casein (CSN1S1) and thyroglobulin (TG) genes have previously
      been associated with fat distribution in cattle. Determining the nature of these
      genetic associations (additive, recessive, or dominant) has been difficult,
      because both markers have small minor allele frequencies in most beef cattle
      populations. This results in few animals homozygous for the minor alleles.
      selection to increase the frequencies of the minor alleles for 2 SNP markers in
      these genes was undertaken in a composite population. The objective was to obtain
      better estimates of genetic effects associated with these markers and determine
      if there were epistatic interactions. Selection increased the frequencies of
      minor alleles for both SNP from <0.30 to 0.45. Bulls (n = 24) heterozygous for
      both SNP were used in 3 yr to produce 204 steer progeny harvested at an average
      age of 474 d. The combined effect of the 9 CSN1S1 * TG genotypes was associated
      with carcass-adjusted fat thickness (P < 0.06) and meat tenderness predicted at
      the abattoir by visible and near-infrared reflectance spectroscopy (P < 0.04).
      Genotype did not affect BW from birth through harvest, ribeye area, marbling
      score, slice shear force, or image-based yield grade (P > 0.10). Additive,
      dominance, and epistatic SNP association effects were estimated from genotypic
      effects for adjusted fat thickness and predicted meat tenderness. Adjusted fat
      thickness showed a dominance association with TG SNP (P < 0.06) and an epistatic
      additive CSN1S1 * additive TG association (P < 0.03). For predicted meat
      tenderness, heterozygous TG meat was more tender than meat from either homozygote
      (P < 0.002). Dominance and epistatic associations can result in different SNP
      allele substitution effects in populations where SNP have the same linkage
      disequilibrium with causal mutations but have different frequencies. Although the
      complex associations estimated in this study would contribute little to within
      population selection response, they could be important for marker-assisted
      management or reciprocal selection schemes.

PMID- 23148259
TI  - Detection of QTL controlling metabolism, meat quality, and liver quality traits
      of the overfed interspecific hybrid mule duck.
AB  - The mule duck, an interspecific hybrid obtained by crossing common duck (Anas
      platyrhynchos) females with Muscovy (Cairina moschata) drakes, is widely used for
      fatty liver production. The purpose of the present study was to detect and map
      single and pleiotropic QTL that segregate in the common duck species, and
      influence the expression of traits in their overfed mule duck offspring. To this
      end, we generated a common duck backcross (BC) population by crossing Kaiya and
      heavy Pekin experimental lines, which differ notably in regard to the BW and
      overfeeding ability of their mule progeny. The BC females were mated to Muscovy
      drakes and, on average, 4 male mule ducks hatched per BC female (1600 in total)
      and were measured for growth, metabolism during growth and the overfeeding
      period, overfeeding ability, and the quality of their breast meat and fatty
      liver. The phenotypic value of BC females was estimated for each trait by
      assigning to each female the mean value of the phenotypes of her offspring.
      Estimations allowed for variance, which depended on the number of male offspring
      per BC and the heritability of the trait considered. The genetic map used for QTL
      detection consisted of 91 microsatellite markers aggregated into 16 linkage
      groups (LG) covering a total of 778 cM. Twenty-two QTL were found to be
      significant at the 1% chromosome-wide threshold level using the single-trait
      detection option of the QTLMap software. Most of the QTL detected were related to
      the quality of breast meat and fatty liver: QTL for meat pH 20 min post mortem
      were mapped to LG4 (at the 1% genome-wide significance level), and QTL for meat
      lipid content and cooking losses were mapped to LG2a. The QTL related to fatty
      liver weight and liver protein and lipid content were for the most part detected
      on LG2c and LG9. Multitrait analysis highlighted the pleiotropic effects of QTL
      in these chromosome regions. Apart from the strong QTL for plasma triglyceride
      content at the end of the overfeeding period mapped to chromosome Z using single
      trait analysis, all metabolic trait QTL were detected with the multitrait
      approach: the QTL mapped to LG14 and LG21 affected the plasma cholesterol and
      triglyceride contents, whereas the QTL mapped to LG2a seemed to impact glycemia
      and the basal plasma corticosterone content. A greater density genetic map will
      be needed to further fine map the QTL.

PMID- 23148260
TI  - Preferential binding of K+ ions in the selectivity filter at equilibrium explains
      high selectivity of K+ channels.
AB  - K(+) channels exhibit strong selectivity for K(+) ions over Na(+) ions based on
      electrophysiology experiments that measure ions competing for passage through the
      channel. During this conduction process, multiple ions interact within the region
      of the channel called the selectivity filter. Ion selectivity may arise from an
      equilibrium preference for K(+) ions within the selectivity filter or from a
      kinetic mechanism whereby Na(+) ions are precluded from entering the selectivity
      filter. Here, we measure the equilibrium affinity and selectivity of K(+) and
      Na(+) ions binding to two different K(+) channels, KcsA and MthK, using
      isothermal titration calorimetry. Both channels exhibit a large preference for
      K(+) over Na(+) ions at equilibrium, in line with electrophysiology recordings of
      reversal potentials and Ba(2+) block experiments used to measure the selectivity
      of the external-most ion-binding sites. These results suggest that the high
      selectivity observed during ion conduction can originate from a strong
      equilibrium preference for K(+) ions in the selectivity filter, and that K(+)
      selectivity is an intrinsic property of the filter. We hypothesize that the
      equilibrium preference for K(+) ions originates in part through the optimal
      spacing between sites to accommodate multiple K(+) ions within the selectivity
      filter.

PMID- 23148261
TI  - Dissecting a regulatory calcium-binding site of CLC-K kidney chloride channels.
AB  - The kidney and inner ear CLC-K chloride channels, which are involved in salt
      absorption and endolymph production, are regulated by extracellular Ca(2+) in the
      millimolar concentration range. Recently, Gradogna et al. (2010. J. Gen. Physiol.
      http://dx.doi.org/10.1085/jgp.201010455) identified a pair of acidic residues
      (E261 and D278) located in the loop between helices I and J as forming a putative
      intersubunit Ca(2+)-binding site in hClC-Ka. In this study, we sought to explore
      the properties of the binding site in more detail. First, we verified that the
      site is conserved in hClC-Kb and rClC-K1. In addition, we could confer Ca(2+)
      sensitivity to the Torpedo marmorata ClC-0 channel by exchanging its I-J loop
      with that from ClC-Ka, demonstrating a direct role of the loop in Ca(2+) binding.
      Based on a structure of a bacterial CLC and a new sequence alignment, we built
      homology models of ClC-Ka. The models suggested additional amino acids involved
      in Ca(2+) binding. Testing mutants of these residues, we could restrict the range
      of plausible models and positively identify two more residues (E259 and E281)
      involved in Ca(2+) coordination. To investigate cation specificity, we applied
      extracellular Zn(2+), Mg(2+), Ba(2+), Sr(2+), and Mn(2+). Zn(2+) blocks ClC-Ka as
      well as its Ca(2+)-insensitive mutant, suggesting that Zn(2+) binds to a
      different site. Mg(2+) does not activate CLC-Ks, but the channels are activated
      by Ba(2+), Sr(2+), and Mn(2+) with a rank order of potency of Ca(2+) > Ba(2+) >
      Sr(2+) = Mn(2+) for the human CLC-Ks. Dose-response analysis indicates that the
      less potent Ba(2+) has a lower affinity rather than a lower efficacy.
      Interestingly, rClC-K1 shows an altered rank order (Ca(2+) > Sr(2+) >> Ba(2+)),
      but homology models suggest that residues outside the I-J loop are responsible
      for this difference. Our detailed characterization of the regulatory Ca(2+)
      binding site provides a solid basis for the understanding of the physiological
      modulation of CLC-K channel function in the kidney and inner ear.

PMID- 23148263
TI  - Integrating current knowledge in various aspects of thylakoid membrane structure
      and dynamics.

PMID- 23148264
TI  - Lateral heterogeneity of plant thylakoid protein complexes: early reminiscences.
AB  - The concept that the two photosystems of photosynthesis cooperate in series,
      immortalized in Hill and Bendall's Z scheme, was still a black box that defined
      neither the structural nor the molecular organization of the thylakoid membrane
      network into grana and stroma thylakoids. The differentiation of the continuous
      thylakoid membrane into stacked grana thylakoids interconnected by single stroma
      thylakoids is a morphological reflection of the non-random distribution of
      photosystem II/light-harvesting complex of photosystem II, photosystem I and ATP
      synthase, which became known as lateral heterogeneity.

PMID- 23148262
TI  - Permeant calcium ion feed-through regulation of single inositol 1,4,5
      trisphosphate receptor channel gating.
AB  - The ubiquitous inositol 1,4,5-trisphosphate (InsP(3)) receptor (InsP(3)R) Ca(2+)
      release channel plays a central role in the generation and modulation of
      intracellular Ca(2+) signals, and is intricately regulated by multiple mechanisms
      including cytoplasmic ligand (InsP(3), free Ca(2+), free ATP(4-)) binding,
      posttranslational modifications, and interactions with cytoplasmic and
      endoplasmic reticulum (ER) luminal proteins. However, regulation of InsP(3)R
      channel activity by free Ca(2+) in the ER lumen ([Ca(2+)](ER)) remains poorly
      understood because of limitations of Ca(2+) flux measurements and imaging
      techniques. Here, we used nuclear patch-clamp experiments in excised luminal-side
      out configuration with perfusion solution exchange to study the effects of
      [Ca(2+)](ER) on homotetrameric rat type 3 InsP(3)R channel activity. In optimal
      [Ca(2+)](i) and subsaturating [InsP(3)], jumps of [Ca(2+)](ER) from 70 nM to 300
      uM reduced channel activity significantly. This inhibition was abrogated by
      saturating InsP(3) but restored when [Ca(2+)](ER) was raised to 1.1 mM. In
      suboptimal [Ca(2+)](i), jumps of [Ca(2+)](ER) (70 nM to 300 uM) enhanced channel
      activity. Thus, [Ca(2+)](ER) effects on channel activity exhibited a biphasic
      dependence on [Ca(2+)](i). In addition, the effect of high [Ca(2+)](ER) was
      attenuated when a voltage was applied to oppose Ca(2+) flux through the channel.
      These observations can be accounted for by Ca(2+) flux driven through the open
      InsP(3)R channel by [Ca(2+)](ER), raising local [Ca(2+)](i) around the channel to
      regulate its activity through its cytoplasmic regulatory Ca(2+)-binding sites.
      Importantly, [Ca(2+)](ER) regulation of InsP(3)R channel activity depended on
      cytoplasmic Ca(2+)-buffering conditions: it was more pronounced when [Ca(2+)](i)
      was weakly buffered but completely abolished in strong Ca(2+)-buffering
      conditions. With strong cytoplasmic buffering and Ca(2+) flux sufficiently
      reduced by applied voltage, both activation and inhibition of InsP(3)R channel
      gating by physiological levels of [Ca(2+)](ER) were completely abolished.
      Collectively, these results rule out Ca(2+) regulation of channel activity by
      direct binding to the luminal aspect of the channel.

PMID- 23148265
TI  - Characterization of PSII-LHCII supercomplexes isolated from pea thylakoid
      membrane by one-step treatment with alpha- and beta-dodecyl-D-maltoside.
AB  - It was the work of Jan Anderson, together with Keith Boardman, that showed it was
      possible to physically separate photosystem I (PSI) from photosystem II (PSII),
      and it was Jan Anderson who realized the importance of this work in terms of the
      fluid-mosaic model as applied to the thylakoid membrane. Since then, there has
      been a steady progress in the development of biochemical procedures to isolate
      PSII and PSI both for physical and structural studies. Dodecylmaltoside (DM) has
      emerged as an effective mild detergent for this purpose. DM is a glucoside-based
      surfactant with a bulky hydrophilic head group composed of two sugar rings and a
      non-charged alkyl glycoside chain. Two isomers of this molecule exist, differing
      only in the configuration of the alkyl chain around the anomeric centre of the
      carbohydrate head group, axial in alpha-DM and equatorial in beta-DM. We have
      compared the use of alpha-DM and beta-DM for the isolation of supramolecular
      complexes of PSII by a single-step solubilization of stacked thylakoid membranes
      isolated from peas. As a result, we have optimized conditions to obtain
      homogeneous preparations of the C(2)S(2)M(2) and C(2)S(2) supercomplexes
      following the nomenclature of Dekker & Boekema (2005 Biochim. Biophys. Acta 1706,
      12-39). These PSII-LHCII supercomplexes were subjected to biochemical and
      structural analyses.

PMID- 23148266
TI  - The evolution of photosystem I in light of phage-encoded reaction centres.
AB  - Recent structural determinations and metagenomic studies shed light on the
      evolution of photosystem I (PSI) from the homodimeric reaction centre of
      primitive bacteria to plant PSI at the top of the evolutionary development. The
      evolutionary scenario of over 3.5 billion years reveals an increase in the
      complexity of PSI. This phenomenon of ever-increasing complexity is common to all
      evolutionary processes that in their advanced stages are highly dependent on fine
      tuning of regulatory processes. On the other hand, the recently discovered virus
      encoded PSI complexes contain a minimal number of subunits. This may reflect the
      unique selection scenarios associated with viral replication. It may be
      beneficial for future engineering of productive processes to utilize 'primitive'
      complexes that disregard the cellular regulatory processes and to avoid those
      regulatory constraints when our goal is to divert the process from its original
      route. In this article, we discuss the evolutionary forces that act on viral
      reaction centres and the role of the virus-carried photosynthetic genes in the
      evolution of photosynthesis.

PMID- 23148267
TI  - Lipid functions in cytochrome bc complexes: an odd evolutionary transition in a
      membrane protein structure.
AB  - Lipid-binding sites and properties were compared in the hetero-oligomeric
      cytochrome (cyt) b(6)f and the yeast bc(1) complexes that function, respectively,
      in photosynthetic and respiratory electron transport. Seven lipid-binding sites
      in the monomeric unit of the dimeric cyanobacterial b(6)f complex overlap four
      sites in the Chlamydomonas reinhardtii algal b(6)f complex and four in the yeast
      bc(1) complex. The proposed lipid functions include: (i) interfacial-interhelix
      mediation between (a) the two 8-subunit monomers of the dimeric complex, (b)
      between the core domain (cyt b, subunit IV) and the six trans membrane helices of
      the peripheral domain (cyt f, iron-sulphur protein (ISP), and four small subunits
      in the boundary 'picket fence'); (ii) stabilization of the ISP domain-swapped
      trans-membrane helix; (iii) neutralization of basic residues in the single helix
      of cyt f and of the ISP; (iv) a 'latch' to photosystem I provided by the beta
      carotene chain protruding through the 'picket fence'; (v) presence of a lipid and
      chlorophyll a chlorin ring in b(6)f in place of the eighth helix in the bc(1) cyt
      b polypeptide. The question is posed of the function of the lipid substitution in
      relation to the evolutionary change between the eight and seven helix structures
      of the cyt b polypeptide. On the basis of the known n-side activation of light
      harvesting complex II (LHCII) kinase by the p-side level of plastoquinol, one
      possibility is that the change was directed by the selective advantage of p- to n
      side trans membrane signalling functions in b(6)f, with the lipid either
      mediating this function or substituting for the trans membrane helix of a
      signalling protein lost in crystallization.

PMID- 23148268
TI  - Structure of the dimeric RC-LH1-PufX complex from Rhodobaca bogoriensis
      investigated by electron microscopy.
AB  - Electron microscopy and single-particle averaging were performed on isolated
      reaction centre (RC)-antenna complexes (RC-LH1-PufX complexes) of Rhodobaca
      bogoriensis strain LBB1, with the aim of establishing the LH1 antenna
      conformation, and, in particular, the structural role of the PufX protein.
      Projection maps of dimeric complexes were obtained at 13 A resolution and show
      the positions of the 2 * 14 LH1 alpha- and beta-subunits. This new dimeric
      complex displays two open, C-shaped LH1 aggregates of 13 alphabeta polypeptides
      partially surrounding the RCs plus two LH1 units forming the dimer interface in
      the centre. Between the interface and the two half rings are two openings on each
      side. Next to the openings, there are four additional densities present per
      dimer, considered to be occupied by four copies of PufX. The position of the RC
      in our model was verified by comparison with RC-LH1-PufX complexes in membranes.
      Our model differs from previously proposed configurations for Rhodobacter species
      in which the LH1 ribbon is continuous in the shape of an S, and the stoichiometry
      is of one PufX per RC.

PMID- 23148269
TI  - Regulatory factors for the assembly of thylakoid membrane protein complexes.
AB  - Major multi-protein photosynthetic complexes, located in thylakoid membranes, are
      responsible for the capture of light and its conversion into chemical energy in
      oxygenic photosynthetic organisms. Although the structures and functions of these
      photosynthetic complexes have been explored, the molecular mechanisms underlying
      their assembly remain elusive. In this review, we summarize current knowledge of
      the regulatory components involved in the assembly of thylakoid membrane protein
      complexes in photosynthetic organisms. Many of the known regulatory factors are
      conserved between prokaryotes and eukaryotes, whereas others appear to be newly
      evolved or to have expanded predominantly in eukaryotes. Their specific features
      and fundamental differences in cyanobacteria, green algae and land plants are
      discussed.

PMID- 23148270
TI  - Modulation of the light-harvesting chlorophyll antenna size in Chlamydomonas
      reinhardtii by TLA1 gene over-expression and RNA interference.
AB  - Truncated light-harvesting antenna 1 (TLA1) is a nuclear gene proposed to
      regulate the chlorophyll (Chl) antenna size in Chlamydomonas reinhardtii. The Chl
      antenna size of the photosystems and the chloroplast ultrastructure were
      manipulated upon TLA1 gene over-expression and RNAi downregulation. The TLA1 over
      expressing lines possessed a larger chlorophyll antenna size for both
      photosystems and contained greater levels of Chl b per cell relative to the wild
      type. Conversely, TLA1 RNAi transformants had a smaller Chl antenna size for both
      photosystems and lower levels of Chl b per cell. Western blot analyses of the
      TLA1 over-expressing and RNAi transformants showed that modulation of TLA1 gene
      expression was paralleled by modulation in the expression of light-harvesting
      protein, reaction centre D1 and D2, and VIPP1 genes. Transmission electron
      microscopy showed that modulation of TLA1 gene expression impacts the
      organization of thylakoid membranes in the chloroplast. Over-expressing lines
      showed well-defined grana, whereas RNAi transformants possessed loosely held
      together and more stroma-exposed thylakoids. Cell fractionation suggested
      localization of the TLA1 protein in the inner chloroplast envelope and
      potentially in association with nascent thylakoid membranes, indicating a role in
      Chl antenna assembly and thylakoid membrane biogenesis. The results provide a
      mechanistic understanding of the Chl antenna size regulation by the TLA1 gene.

PMID- 23148271
TI  - Subunit composition of CP43-less photosystem II complexes of Synechocystis sp.
      PCC 6803: implications for the assembly and repair of photosystem II.
AB  - Photosystem II (PSII) mutants are useful experimental tools to trap potential
      intermediates involved in the assembly of the oxygen-evolving PSII complex. Here,
      we focus on the subunit composition of the RC47 assembly complex that accumulates
      in a psbC null mutant of the cyanobacterium Synechocystis sp. PCC 6803 unable to
      make the CP43 apopolypeptide. By using native gel electrophoresis, we showed that
      RC47 is heterogeneous and mainly found as a monomer of 220 kDa. RC47 complexes co
      purify with small Cab-like proteins (ScpC and/or ScpD) and with Psb28 and its
      homologue Psb28-2. Analysis of isolated His-tagged RC47 indicated the presence of
      D1, D2, the CP47 apopolypeptide, plus nine of the 13 low-molecular-mass (LMM)
      subunits found in the PSII holoenzyme, including PsbL, PsbM and PsbT, which lie
      at the interface between the two momomers in the dimeric holoenzyme. Not detected
      were the LMM subunits (PsbK, PsbZ, Psb30 and PsbJ) located in the vicinity of
      CP43 in the holoenzyme. The photochemical activity of isolated RC47-His
      complexes, including the rate of reduction of P680(+), was similar to that of
      PSII complexes lacking the Mn(4)CaO(5) cluster. The implications of our results
      for the assembly and repair of PSII in vivo are discussed.

PMID- 23148272
TI  - Optimization of light harvesting and photoprotection: molecular mechanisms and
      physiological consequences.
AB  - The distinctive lateral organization of the protein complexes in the thylakoid
      membrane investigated by Jan Anderson and co-workers is dependent on the balance
      of various attractive and repulsive forces. Modulation of these forces allows
      critical physiological regulation of photosynthesis that provides efficient light
      harvesting in limiting light but dissipation of excess potentially damaging
      radiation in saturating light. The light-harvesting complexes (LHCII) are central
      to this regulation, which is achieved by phosphorylation of stromal residues,
      protonation on the lumen surface and de-epoxidation of bound violaxanthin. The
      functional flexibility of LHCII derives from a remarkable pigment composition and
      configuration that not only allow efficient absorption of light and efficient
      energy transfer either to photosystem II or photosystem I core complexes, but
      through subtle configurational changes can also exhibit highly efficient
      dissipative reactions involving chlorophyll-xanthophyll and/or chlorophyll
      chlorophyll interactions. These changes in function are determined at a
      macroscopic level by alterations in protein-protein interactions in the thylakoid
      membrane. The capacity and dynamics of this regulation are tuned to different
      physiological scenarios by the exact protein and pigment content of the light
      harvesting system. Here, the molecular mechanisms involved will be reviewed, and
      the optimization of the light-harvesting system in different environmental
      conditions described.

PMID- 23148273
TI  - Protein kinases and phosphatases involved in the acclimation of the
      photosynthetic apparatus to a changing light environment.
AB  - Photosynthetic organisms are subjected to frequent changes in light quality and
      quantity and need to respond accordingly. These acclimatory processes are
      mediated to a large extent through thylakoid protein phosphorylation. Recently,
      two major thylakoid protein kinases have been identified and characterized. The
      Stt7/STN7 kinase is mainly involved in the phosphorylation of the LHCII antenna
      proteins and is required for state transitions. It is firmly associated with the
      cytochrome b(6)f complex, and its activity is regulated by the redox state of the
      plastoquinone pool. The other kinase, Stl1/STN8, is responsible for the
      phosphorylation of the PSII core proteins. Using a reverse genetics approach, we
      have recently identified the chloroplast PPH1/TAP38 and PBPC protein
      phosphatases, which counteract the activity of STN7 and STN8 kinases,
      respectively. They belong to the PP2C-type phosphatase family and are conserved
      in land plants and algae. The picture that emerges from these studies is that of
      a complex regulatory network of chloroplast protein kinases and phosphatases that
      is involved in light acclimation, in maintenance of the plastoquinone redox poise
      under fluctuating light and in the adjustment to metabolic needs.

PMID- 23148274
TI  - Redox regulation of photosynthetic gene expression.
AB  - Redox chemistry and redox regulation are central to the operation of
      photosynthesis and respiration. However, the roles of different oxidants and
      antioxidants in the regulation of photosynthetic or respiratory gene expression
      remain poorly understood. Leaf transcriptome profiles of a range of Arabidopsis
      thaliana genotypes that are deficient in either hydrogen peroxide processing
      enzymes or in low molecular weight antioxidant were therefore compared to
      determine how different antioxidant systems that process hydrogen peroxide
      influence transcripts encoding proteins targeted to the chloroplasts or
      mitochondria. Less than 10 per cent overlap was observed in the transcriptome
      patterns of leaves that are deficient in either photorespiratory (catalase
      (cat)2) or chloroplastic (thylakoid ascorbate peroxidase (tapx)) hydrogen
      peroxide processing. Transcripts encoding photosystem II (PSII) repair cycle
      components were lower in glutathione-deficient leaves, as were the thylakoid
      NAD(P)H (nicotinamide adenine dinucleotide (phosphate)) dehydrogenases (NDH)
      mRNAs. Some thylakoid NDH mRNAs were also less abundant in tAPX-deficient and
      ascorbate-deficient leaves. Transcripts encoding the external and internal
      respiratory NDHs were increased by low glutathione and low ascorbate. Regulation
      of transcripts encoding specific components of the photosynthetic and respiratory
      electron transport chains by hydrogen peroxide, ascorbate and glutathione may
      serve to balance non-cyclic and cyclic electron flow pathways in relation to
      oxidant production and reductant availability.

PMID- 23148276
TI  - Acclimation of leaves to low light produces large grana: the origin of the
      predominant attractive force at work.
AB  - Photosynthetic membrane sacs (thylakoids) of plants form granal stacks
      interconnected by non-stacked thylakoids, thereby being able to fine-tune (i)
      photosynthesis, (ii) photoprotection and (iii) acclimation to the environment.
      Growth in low light leads to the formation of large grana, which sometimes
      contain as many as 160 thylakoids. The net surface charge of thylakoid membranes
      is negative, even in low-light-grown plants; so an attractive force is required
      to overcome the electrostatic repulsion. The theoretical van der Waals attraction
      is, however, at least 20-fold too small to play the role. We determined the
      enthalpy change, in the spontaneous stacking of previously unstacked thylakoids
      in the dark on addition of Mg(2+), to be zero or marginally positive
      (endothermic). The Gibbs free-energy change for the spontaneous process is
      necessarily negative, a requirement that can be met only by an increase in
      entropy for an endothermic process. We conclude that the dominant attractive
      force in thylakoid stacking is entropy-driven. Several mechanisms for increasing
      entropy upon stacking of thylakoid membranes in the dark, particularly in low
      light plants, are discussed. In the light, which drives the chloroplast far away
      from equilibrium, granal stacking accelerates non-cyclic photophosphorylation,
      possibly enhancing the rate at which entropy is produced.

PMID- 23148275
TI  - Regulation of the photosynthetic apparatus under fluctuating growth light.
AB  - Safe and efficient conversion of solar energy to metabolic energy by plants is
      based on tightly inter-regulated transfer of excitation energy, electrons and
      protons in the photosynthetic machinery according to the availability of light
      energy, as well as the needs and restrictions of metabolism itself. Plants have
      mechanisms to enhance the capture of energy when light is limited for growth and
      development. Also, when energy is in excess, the photosynthetic machinery slows
      down the electron transfer reactions in order to prevent the production of
      reactive oxygen species and the consequent damage of the photosynthetic
      machinery. In this opinion paper, we present a partially hypothetical scheme
      describing how the photosynthetic machinery controls the flow of energy and
      electrons in order to enable the maintenance of photosynthetic activity in nature
      under continual fluctuations in white light intensity. We discuss the roles of
      light-harvesting II protein phosphorylation, thermal dissipation of excess energy
      and the control of electron transfer by cytochrome b(6)f, and the role of
      dynamically regulated turnover of photosystem II in the maintenance of the
      photosynthetic machinery. We present a new hypothesis suggesting that most of the
      regulation in the thylakoid membrane occurs in order to prevent oxidative damage
      of photosystem I.

PMID- 23148277
TI  - From ecophysiology to phenomics: some implications of photoprotection and shade
      sun acclimation in situ for dynamics of thylakoids in vitro.
AB  - Half a century of research into the physiology and biochemistry of sun-shade
      acclimation in diverse plants has provided reality checks for contemporary
      understanding of thylakoid membrane dynamics. This paper reviews recent insights
      into photosynthetic efficiency and photoprotection from studies of two
      xanthophyll cycles in old shade leaves from the inner canopy of the tropical
      trees Inga sapindoides and Persea americana (avocado). It then presents new
      physiological data from avocado on the time frames of the slow coordinated
      photosynthetic development of sink leaves in sunlight and on the slow renovation
      of photosynthetic properties in old leaves during sun to shade and shade to sun
      acclimation. In so doing, it grapples with issues in vivo that seem relevant to
      our increasingly sophisticated understanding of DeltapH-dependent, xanthophyll
      pigment-stabilized non-photochemical quenching in the antenna of PSII in
      thylakoid membranes in vitro.

PMID- 23148278
TI  - Towards elucidation of dynamic structural changes of plant thylakoid
      architecture.
AB  - Long-term acclimation of shade versus sun plants modulates the composition,
      function and structural organization of the architecture of the thylakoid
      membrane network. Significantly, these changes in the macroscopic structural
      organization of shade and sun plant chloroplasts during long-term acclimation are
      also mimicked following rapid transitions in irradiance: reversible
      ultrastructural changes in the entire thylakoid membrane network increase the
      number of grana per chloroplast, but decrease the number of stacked thylakoids
      per granum in seconds to minutes in leaves. It is proposed that these dynamic
      changes depend on reversible macro-reorganization of some light-harvesting
      complex IIb and photosystem II supracomplexes within the plant thylakoid network
      owing to differential phosphorylation cycles and other biochemical changes known
      to ensure flexibility in photosynthetic function in vivo. Some lingering grana
      enigmas remain: elucidation of the mechanisms involved in the dynamic
      architecture of the thylakoid membrane network under fluctuating irradiance and
      its implications for function merit extensive further studies.

PMID- 23148279
TI  - Vitamin A supplementation, serum lipids, liver enzymes and C-reactive protein
      concentrations in obese women of reproductive age.
AB  - BACKGROUND: High-dose vitamin A influences glucose and lipid profile; however,
      the possible effects of moderate doses (25,000 IU/d) are conflicting. We aimed to
      compare the effect of vitamin A supplementation on several anthropometric and
      biochemical variables between obese and non-obese women. METHODS: This study was
      performed on 84 women among whom 56 were obese (body mass index [BMI] 30-35
      kg/m(2)) and 28 were non-obese (BMI 18.5-24.9 kg/m(2)). Obese women were randomly
      divided into two groups: one group received 25,000 IU/d retinyl palmitate and
      another group received placebo. The third group was age-matched non-obese women
      who received 25,000 IU/d retinyl palmitate. At baseline and four months after
      intervention, fasting blood glucose (FBG), lipid profile, C-reactive protein
      (CRP) and liver enzymes were evaluated. RESULTS: Baseline concentrations of serum
      FBG and triglyceride in the obese vitamin A-treated group were significantly
      higher compared with the other groups (P = 0.004 and 0.007, respectively). A
      significant increase in serum FBG (P = 0.026), total cholesterol (TC) (P = 0.004)
      and low-density lipoprotein cholesterol (LDL-C) (P = 0.016) in the non-obese
      group and a significant decrease in serum high-density lipoprotein cholesterol
      (HDL-C) (P = 0.001) in the obese group was observed. Serum CRP increased
      significantly in the obese vitamin A-treated group (P = 0.03) and serum aspartate
      transaminase increased significantly in the obese and non-obese groups after
      vitamin A supplementation (P = 0.008 and 0.001, respectively). CONCLUSIONS:
      Treatment with 25,000 IU/d vitamin A induced a mild elevation in serum lipids,
      CRP and liver enzymes in obese and non-obese women. Considering the other
      information about possible side-effects of excess vitamin A, use of vitamin A in
      this dose and duration should be considered with caution.

PMID- 23148280
TI  - Pioglitazone protects HDL(2&3) against oxidation in overweight and obese men.
AB  - BACKGROUND: The worldwide epidemic of obesity is a major public health concern
      and is persuasively linked to the rising prevalence of diabetes and
      cardiovascular disease. Obesity is often associated with an abnormal lipoprotein
      profile, which may be partly negated by pioglitazone intervention, as this can
      influence the composition and oxidation characteristics of low-density
      lipoprotein (LDL). However, as pioglitazone's impact on these parameters within
      high-density lipoprotein (HDL), specifically HDL(2&3), is absent from the
      literature, this study was performed to address this shortcoming. METHODS: Twenty
      men were randomized to placebo or pioglitazone (30 mg/day) for 12 weeks. HDL(2&3)
      were isolated by rapid-ultracentrifugation. HDL(2&3)-cholesterol and phospholipid
      content were assessed by enzymatic assays and apolipoprotein AI (apoAI) content
      by single-radial immunodiffusion. HDL(2&3) oxidation characteristics were
      assessed by monitoring conjugated diene production and paraoxonase-1 activity by
      spectrophotometric assays. RESULTS: Compared with the placebo group, pioglitazone
      influenced the composition and oxidation potential of HDL(2&3). Specifically,
      total cholesterol (P < 0.05), phospholipid (P < 0.001) and apoAI (P < 0.001) were
      enriched within HDL(2). Furthermore, the resistance of HDL(2&3) to oxidation (P <
      0.05) and the activity of paroxonase-1 were also increased (P < 0.001).
      CONCLUSIONS: Overall, these findings indicate that pioglitazone treatment induced
      antiatherogenic changes within HDL(2&3), which may help reduce the incidence of
      premature cardiovascular disease linked with obesity.

PMID- 23148281
TI  - Impact of prandial status on the comparison of capillary glucose meter and venous
      plasma glucose measurements in healthy volunteers.
AB  - BACKGROUND: There is a negative glucose gradient between the capillary and venous
      systems, produced by glucose uptake into peripheral tissues. This gradient is
      augmented by oral glucose ingestion in healthy volunteers; thus prandial status
      may impact on capillary glucose meter performance. Our primary aim was to
      investigate whether the (capillary-venous plasma) glucose difference changed in
      relation to prandial status, in healthy volunteers. METHODS: Glucose was measured
      fasting and also one hour after an ad libitum breakfast, in 103 healthy
      volunteers. Duplicate capillary (finger stick) measurements were undertaken at
      both time points, using both the FreeStyle Lite and AccuChek Performa meters.
      Simultaneous venous (antecubital fossa) samples were centrifuged immediately
      after collection and plasma glucose was measured using the laboratory hexokinase
      method. Results were compared by Bland-Altman difference analysis. RESULTS: The
      mean (95% CI) pre- and postprandial (capillary-plasma) glucose differences
      (mmol/L) were calculated for each meter. For the Freestyle Lite, the preprandial
      difference was -0.51 (-0.58 to -0.45) and postprandial difference was 0.81 (0.69
      0.94). Corresponding differences for the Performa were -0.13 (-0.20 to -0.06) and
      1.19 (1.07-1.31), respectively. T-test comparison of participants' paired pre-
      and postprandial (capillary-plasma) glucose differences confirmed a significant
      meal-related change in glucose estimation for both meters (P < 0.0001). Also,
      both meters read highest at lower glucose concentrations. CONCLUSIONS: In healthy
      volunteers, both glucose meters showed a systematic positive bias one hour after
      breakfast. The significance of this finding in diabetes remains to be determined.

PMID- 23148282
TI  - Relationship of total 25-OH vitamin D concentrations to Indices of Multiple
      Deprivation: geoanalysis of laboratory results.
AB  - BACKGROUND: Vitamin D deficiency appears to be widespread and associated with
      ethnicity and economic status. Geography is the key to virtually all national
      statistics. It provides a structure for collecting, processing, storing and
      aggregating data. Linking geographic data to laboratory data allows analysis of
      the association of laboratory data with economic indicators. METHODS: The
      laboratory information system was searched to create a data-set of total 25-OH
      vitamin D concentrations, which was then linked to economic (Indices of Multiple
      Deprivation [IMD]) and ethnicity data using postcodes geocoded to Lower Super
      Output Areas (LSOAs). RESULTS: A total of 12422 25-OH vitamin D requests were
      received during the time period searched. A total of 12167 of these had
      associated postcodes that would allow georeferencing to LSOAs. The median total
      25-OH vitamin D was 24.5 nmol/L (5.3-99.0; 2.5-97.5th percentile). Statistically
      significant (Spearman rank) correlations were found between median 25-OH vitamin
      D (nmol/L) and percentage of non-White population and percentage of non-White
      population and IMD. No statistically significant correlation between median 25-OH
      vitamin D concentration and IMD was found; however, a statistically significant
      correlation between percentage of population classified as severely deficient and
      IMD was found. CONCLUSIONS: In summary, vitamin D deficiency is widespread and is
      related to ethnicity; it does not appear to be related to economic status except
      in cases of severe vitamin D deficiency.

PMID- 23148283
TI  - Interleukin 33 mediates type 2 immunity and inflammation in the central nervous
      system of mice infected with Angiostrongylus cantonensis.
AB  - Angiostrongylus cantonensis can induce central nervous system (CNS) injury and
      cause human eosinophilic meningitis. The CNS has been found to have high
      expression of interleukin 33 (IL-33), which promotes the pathogenesis of T-helper
      2 (Th2)-related disease. Given the predominantly type 2 response induced by A.
      cantonensis-infected mice and human, it is likely that IL-33 may play a role in
      aiding this process. We report here that IL-33 protein and ST2L messenger RNA
      (mRNA) transcripts in the brains were upregulated during A. cantonensis infection
      and that both splenocytes and brain mononuclear cells became IL-33 responsive and
      produced interleukin 5 and interleukin 13. Furthermore, administration of IL-33
      to A. cantonensis-infected mice enhanced ST2L expression and cytokine production.
      Interestingly, brain IL-33 protein and ST2L mRNA levels were elevated 14-21 days
      after infection in BALB/c mice, compared with C57BL/6 mice. Thus, our data
      indicate that IL-33 produced in the brain may function as an inflammatory
      mediator in eosinophilic meningitis induced by A. cantonensis.

PMID- 23148284
TI  - Role of seminal shedding of herpesviruses in HIV Type 1 Transmission.
AB  - To investigate the role of genital shedding of herpesviruses in human
      immunodeficiency virus type 1 (HIV) transmission, we compared 20 HIV-infected men
      who did and 26 who did not transmit HIV to their sex partners. As described
      previously, HIV transmission was associated with the potential source partner
      having higher levels of HIV RNA in blood and semen, having lower CD4(+) T cell
      counts, having bacterial coinfections in the genital tract, and not using
      antiretroviral therapy. This study extended these findings by observing
      significant associations between HIV transmission and the following
      characteristics, especially among therapy-naive potential source partners:
      seminal cytomegalovirus (CMV) shedding, seminal Epstein-Barr virus shedding, and
      levels of anti CMV immunoglobulin in blood plasma.

PMID- 23148285
TI  - CD4+ T-cell expansion predicts neutralizing antibody responses to monovalent,
      inactivated 2009 pandemic influenza A(H1N1) virus subtype H1N1 vaccine.
AB  - BACKGROUND: The ability of influenza vaccines to elicit CD4(+) T cells and the
      relationship between induction of CD4(+) T cells and vaccine-induced neutralizing
      antibody responses has been controversial. The emergence of swine-origin 2009
      pandemic influenza A virus subtype H1N1 (A[H1N1]pdm09) provided a unique
      opportunity to examine responses to an influenza vaccine composed of both novel
      and previously encountered antigens and to probe the relationship between B-cell
      and T-cell responses to vaccination. METHODS: We tracked CD4(+) T-cell and
      antibody responses of human subjects vaccinated with monovalent subunit
      A(H1N1)pdm09 vaccine. The specificity and magnitude of the CD4(+) T-cell response
      was evaluated using cytokine enzyme-linked immunosorbent spot assays in
      conjugation with peptide pools representing distinct influenza virus proteins.
      RESULTS: Our studies revealed that vaccination induced readily detectable CD4(+)
      T cells specific for conserved portions of hemagglutinin (HA) and the internal
      viral proteins. Interestingly, expansion of HA-specific CD4(+) T cells was most
      tightly correlated with the antibody response. CONCLUSIONS: These results
      indicate that CD4(+) T-cell expansion may be a limiting factor in development of
      neutralizing antibody responses to pandemic influenza vaccines and suggest that
      approaches to facilitate CD4(+) T-cell recruitment may increase the neutralizing
      antibody produced in response to vaccines against novel influenza strains.

PMID- 23148287
TI  - HIV-1 amino acid changes among participants with virologic failure: associations
      with first-line efavirenz or atazanavir plus ritonavir and disease status.
AB  - BACKGROUND: Although specific human immunodeficiency virus type 1 (HIV-1) drug
      resistance mutations are well studied, little is known about cumulative amino
      acid changes, or how regimen and participant characteristics influence these
      changes. METHODS: In the AIDS Clinical Trials Group randomized study A5202 of
      treatment-naive HIV-infected participants, cumulative HIV-1 amino acid changes
      from pretreatment to virologic failure were evaluated in protease and reverse
      transcriptase (RT) gene sequences. RESULTS: Among 265 participants with virologic
      failure, those assigned atazanavir plus ritonavir (ATV/r) did not have
      significantly more protease changes compared with those assigned efavirenz (EFV)
      (P >= .13). In contrast, participants with virologic failure assigned EFV had
      more RT changes, including and excluding known resistance codons (P < .001). At
      pretreatment, lower CD4 cell count, major resistance, more amino acid mixtures
      (all P < .001), hepatitis C antibody negativity (P = .05), and black
      race/ethnicity (P = .02) were associated with more HIV-1 amino acid changes.
      CONCLUSIONS: Virologic failure following EFV-containing treatment was associated
      with more HIV-1 amino acid changes compared to failure of ATV/r-containing
      treatment. Furthermore, we show that non-drug resistance mutations occurred more
      frequently among those failing EFV, the clinical relevance of which warrants
      further investigation. Pretreatment immunologic status may play a role in viral
      evolution during treatment, as evidenced by increased amino acid changes among
      those with lower pretreatment CD4 count. CLINICAL TRIALS REGISTRATION:
      NCT00118898.

PMID- 23148289
TI  - Low bone mineral density, regardless of HIV status, in men who have sex with men.
AB  - A high prevalence of low bone mineral density (BMD) has been reported among men
      with primary or chronic human immunodeficiency virus (HIV) infection. To gain
      further insight into the contribution of HIV infection, we compared the BMD of 41
      men who have sex with men (MSM) with primary HIV infection, 106 MSM with chronic
      HIV infection, and a control group of 30 MSM without HIV infection. Low BMD,
      defined as a z score of >= 2.0 SDs below the mean at the lumbar spine or hip, was
      highly prevalent in all 3 groups. In the multivariate analyses, HIV infection was
      not associated with BMD, suggesting that low BMD previously reported in HIV
      infected MSM may predate HIV acquisition.

PMID- 23148288
TI  - In vivo germination of Bacillus anthracis spores during murine cutaneous
      infection.
AB  - BACKGROUND: Germination is a key step for successful Bacillus anthracis
      colonization and systemic dissemination. Few data are available on spore
      germination in vivo, and the necessity of spore and host cell interactions to
      initiate germination is unclear. METHODS: To investigate the early interactions
      between B. anthracis spores and cutaneous tissue, spores were inoculated in an
      intraperitoneal cell-free device in guinea pigs or into the pinna of mice.
      Germination and bacterial growth were analyzed through colony-forming unit
      enumeration and electron microscopy. RESULTS: In the guinea pig model,
      germination occurred in vivo in the absence of cell contact. Similarly, in the
      mouse ear, germination started within 15 minutes after inoculation, and
      germinating spores were found in the absence of surrounding cells. Germination
      was not observed in macrophage-rich draining lymph nodes, liver, and spleen.
      Edema and lethal toxin production were not required for germination, as a toxin
      deficient strain was as effective as a Sterne-like strain. B. anthracis growth
      was locally controlled for 6 hours. CONCLUSIONS: Spore germination involving no
      cell interactions can occur in vivo, suggesting that diffusible germinants or
      other signals appear sufficient. Different host tissues display drastic
      differences in germination-triggering capacity. Initial control of bacterial
      growth suggests a therapeutic means to exploit host innate defenses to hinder B.
      anthracis colonization.

PMID- 23148290
TI  - Test performance characteristics of Anti-HEV IgG assays strongly influence
      hepatitis E seroprevalence estimates.
AB  - Hepatitis E virus (HEV) seroprevalences of 0.3%-53% were reported from
      industrialized countries. Because these estimates may be influenced by detection
      assays, this study compares 3 frequently used tests for HEV detection: the MP
      Diagnostics HEV immunoglobulin G (IgG) enzyme-linked immunosorbent assay (ELISA),
      the Axiom Diagnostics HEV IgG enzyme immunoassay (EIA), and the Mikrogen
      recomLine HEV IgG assay. Sera from 200 healthy healthcare workers and 30
      individuals with acute HEV infection were analyzed. Among the healthy
      individuals, HEV IgG was found in 4.5% by the MP Diagnostics assay, in 29.5% by
      the Axiom Diagnostics assay, and in 18% by the Mikrogen assay. Among individuals
      with acute HEV infection, positive results were obtained for 83.3%, 100%, and
      96.7%, respectively. Thus, the 3 assays show clear differences in diagnostic
      sensitivity.

PMID- 23148286
TI  - Impact of UGT1A1 Gilbert variant on discontinuation of ritonavir-boosted
      atazanavir in AIDS Clinical Trials Group Study A5202.
AB  - The UGT1A1*28 variant has been associated with hyperbilirubinemia and atazanavir
      discontinuation. Protocol A5202 randomly assigned human immunodeficiency virus
      type 1 (HIV-1)-infected patients to receive atazanavir/ritonavir (atazanavir/r)
      or efavirenz, with tenofovir/emtricitabine or abacavir/lamivudine. A total of 646
      atazanavir/r recipients were evaluable for UGT1A1. Homozygosity for *28/*28 was
      present in 8% of whites, 24% of blacks, and 18% of Hispanics and was associated
      with increased bilirubin concentrations. There was an association between *28/*28
      and increased atazanavir/r discontinuation among Hispanic participants (P = .005)
      but not among white or black participants (P = .79 and P = .46, respectively).
      The positive predictive value of 28*/28* for atazanavir/r discontinuation among
      Hispanic participants was only 32% (95% confidence interval, 16%-52%).

PMID- 23148292
TI  - Phosphatidylserine exposure and surface sugars in two Leishmania (Viannia)
      braziliensis strains involved in cutaneous and mucocutaneous leishmaniasis.
AB  - BACKGROUND: Phosphatidylserine (PS) and surface carbohydrates (SC) are known as
      virulence factors that may contribute to the different clinical symptoms ranging
      from self-healing cutaneous leishmaniasis lesions to fatal visceral disease.
      Leishmania (Viannia) braziliensis causes localized cutaneous leishmaniasis (LCL)
      and mucocutaneous leishmaniasis (MCL). METHODS: We analyzed PS exposure and SC
      expression associated with 2 primary L. braziliensis isolates from patients with
      LCL or MCL. The role of PS exposure was also addressed during promastigotes
      phagocytosis by macrophages. RESULTS: We observed higher PS exposure on the
      surface of late stationary growth phase promastigotes from patients with LCL,
      compared with those from patients with MCL, and both strains were alive during PS
      display. Reduction in the infectivity index was observed during macrophage
      interaction with late stationary growth phase promastigotes in which PS was
      blocked by annexin V. The major surface carbohydrates detected on LCL and MCL
      promastigotes were alpha-Man, alpha-Glc, and alpha-Gal. However, alpha-beta
      GalNAc, although observed on the surface of the LCL strain during the late
      stationary growth phase was highly expressed on the surface of early stationary
      growth phase promastigotes. CONCLUSIONS: Our results suggest that PS and SC can
      modulate interactions between Leishmania organisms and host cells and may be
      important for the outcome of the clinical course of diseases caused by L.
      braziliensis.

PMID- 23148291
TI  - CCAAT-enhancer binding protein delta (C/EBPdelta) protects against Klebsiella
      pneumoniae-induced pulmonary infection: potential role for macrophage migration.
AB  - Mounting evidence suggests an important role for CCAAT-enhancer binding protein
      delta (C/EBPdelta) in the acute-phase response after bacterial infection.
      However, whether C/EBPdelta limits pneumonia remains elusive and is the aim of
      this study. Therefore, bacterial outgrowth, inflammatory responses, inflammatory
      cell influx, and survival were assessed in wild-type and C/EBPdelta(-/-) mice
      infected with Klebsiella pneumoniae via the airways. We showed that C/EBPdelta
      expression is highly induced in the lung during pulmonary infection and that
      Klebsiella-induced mortality was significantly increased among C/EBPdelta(-/-)
      mice. Bacterial loads and inflammatory responses were similar in wild-type and
      C/EBPdelta(-/-) mice early during infection, whereas bacterial loads were
      increased in C/EBPdelta(-/-) mice later during infection. Moreover, macrophage
      numbers were reduced in lungs of C/EBPdelta(-/-) mice. In vitro experiments
      showed that C/EBPdelta only slightly affects macrophage function. Our data thus
      show that C/EBPdelta contributes to host defense against Klebsiella-induced
      pneumonia and suggests that C/EBPdelta-dependent macrophage mobilization is a key
      mechanism.

PMID- 23148293
TI  - Association of BST-2 gene variants with HIV disease progression underscores the
      role of BST-2 in HIV type 1 infection.
AB  - We tested bone marrow stromal cell antigen 2 (BST-2) gene variants rs3217318, a
      19-base-pair insertion/deletion polymorphism in the promoter region, and
      rs10415893, a tag single-nucleotide polymorphism in the 3' untranslated region,
      for their association with human immunodeficiency virus type 1 (HIV-1) infection
      and disease progression. The study included 356 subjects exposed to HIV-1 (185
      with and 171 without infection) and 188 controls. The first decrease in the
      CD4(+) T-cell count to <200 cells/uL was used as the primary outcome, whereas the
      primary outcome plus initiation of any antiretroviral treatment was used as a
      secondary composite outcome. Association with progression was found for both
      rs3217318 and rs10415893, following an overdominant model. Diplotype analysis
      revealed faster progression to both outcomes for subjects carrying the
      Delta19_G/i19_A diplotype. Luciferase assay showed that a promoter sequence
      containing the i19 allele had the lowest expression levels, suggesting that i19
      allele carriers could have less BST-2 expression, reducing their capability to
      retain viral particles. These results point to the relevance of BST-2 as a host
      genetic factor modifying HIV-1 disease progression.

PMID- 23148294
TI  - Families, dependencies, and the moral ground of health savings accounts.
AB  - Health Savings Accounts have been marginalized in the West. In Singapore,
      however, they are foundational to the financing of health care. In this brief
      essay, I shall begin to sketch a justification for Health Savings Accounts. The
      family has always been thought of as a mere prolegomena to the polis and to be
      primarily about securing the goods of material life: food, shelter, intimacy. I
      shall first explore the recent scientific literature on the communal nature of
      human thriving and follow it with a phenomenological account of human dependency.
      I shall claim that in securing the material means to sustain life, the family is
      also involved in the creation of the life-world of the child. That means that the
      bare necessities of life met in families are not merely about sustaining bodily
      life but are also part of the meaning-making aspects of life. The family then
      should have recourse to the material means of life-and-death decisions, because
      it is in these life-and-death decisions that the families' life-world of values
      is to be deployed.

PMID- 23148296
TI  - Propofol decreases in vivo binding of 11C-PBR28 to translocator protein (18 kDa)
      in the human brain.
AB  - The PET radioligand (11)C-PBR28 targets translocator protein (18 kDa) (TSPO) and
      is a potential marker of neuroimmune activation in vivo. Although several patient
      populations have been studied using (11)C-PBR28, no investigators have studied
      cognitively impaired patients who would require anesthesia for the PET procedure,
      nor have any reports investigated the effects that anesthesia may have on
      radioligand uptake. The purpose of this study was to determine whether the
      anesthetic propofol alters brain uptake of (11)C-PBR28 in healthy subjects.
      METHODS: Ten healthy subjects (5 men; 5 women) each underwent 2 dynamic brain PET
      scans on the same day, first at baseline and then with intravenous propofol
      anesthesia. The subjects were injected with 680 +/- 14 MBq (mean +/- SD) of (11)C
      PBR28 for each PET scan. Brain uptake was measured as total distribution volume
      (V(T)) using the Logan plot and metabolite-corrected arterial input function.
      RESULTS: Propofol decreased V(T), which corrects for any alteration of metabolism
      of the radioligand, by about 26% (P = 0.011). In line with the decrease in V(T),
      brain time-activity curves showed decreases of about 20% despite a 13% increase
      in plasma area under the curve with propofol. Reduction of V(T) with propofol was
      observed across all brain regions, with no significant region X condition
      interaction (P = 0.40). CONCLUSION: Propofol anesthesia reduces the V(T) of (11)C
      PBR28 by about 26% in the brains of healthy human subjects. Given this finding,
      future studies will measure neuroimmune activation in the brains of autistic
      volunteers and their age and sex-matched healthy controls using propofol
      anesthesia. We recommend that future PET studies using (11)C-PBR28 and
      concomitant propofol anesthesia, as would be required in impaired populations,
      include a control arm to account for the effects of propofol on brain
      measurements of TSPO.

PMID- 23148299
TI  - Reflections on reflex thresholds.

PMID- 23148300
TI  - Validation of diagnostic criteria using gadoxetic acid-enhanced and diffusion
      weighted MR imaging for small hepatocellular carcinoma (<= 2.0 cm) in patients
      with hepatitis-induced liver cirrhosis.
AB  - BACKGROUND: Gadoxetic acid and diffusion-weighted imaging (DWI) is increasingly
      used for the diagnosis of hepatocellular carcinoma (HCC). It is relevant to
      refine the diagnostic parameters for HCC, using state-of-the-art imaging
      techniques. PURPOSE: To validate usefulness of magnetic resonance imaging (MRI)
      criteria with gadoxetic acid-enhanced MRI and DWI for diagnosis of small HCC by
      differentiation from dysplastic nodule (DN) or regenerative nodule (RN) in
      cirrhotic patients with strongly suspected small HCC. MATERIAL AND METHODS: One
      hundred and eight patients with 102 HCCs and 29 benign nodules including 21 DNs
      and two large RNs (<= 2.0 cm), and 40 patients with no HCC underwent gadoxetic
      acid-enhanced MRI and DWI. All patients also underwent MDCT. Index MR criteria
      for HCC were: (i) arterial hyperenhancement and hypointensity on hepatobiliary
      phase (HBP) with hyperintensity on DWI; (ii) hypovascular nodule with
      hyperintensity on DWI; (iii) arterial hyperenhancement and hypointensity on HBP
      without hyperintensity on DWI; (iv) arterial hyperenhancement and either iso- or
      hyperintensity on HBP, with hyperintensity on DWI; and (v) hyperintensity only on
      DWI. According to these criteria, MRI findings for HCCs and benign nodules were
      independently classified by two reviewers. RESULTS: On multidetector-row computed
      tomography, 64 HCCs (62.7%) showed typical features for HCC while 13 (12.8%) were
      not identified. On MRI, 84 HCCs (82.4%) showed arterial hyperenhancement and
      hypointensity on HBP, and hyperintensity on DWI. Eight HCCs were regarded as
      hypovascular HCCs with hyperintensity DWI (category 2). One HCC (0.6 cm in
      diameter) was demonstrated only by DWI. For each observer, 101 (99.0%) and 100
      HCCs (98.0%) were discernible when applying all MRI criteria for HCC,
      respectively. Three DNs also fit the HCC criteria, thus the specificity was 90.9%
      for both observers. CONCLUSION: With the HCC criteria based on combined gadoxetic
      acid-enhanced MRI and DWI, it is possible to reliably diagnose small HCC
      including hypovascular HCCs.

PMID- 23148298
TI  - The retromer complex - endosomal protein recycling and beyond.
AB  - The retromer complex is a vital element of the endosomal protein sorting
      machinery that is conserved across all eukaryotes. Retromer is most closely
      associated with the endosome-to-Golgi retrieval pathway and is necessary to
      maintain an active pool of hydrolase receptors in the trans-Golgi network. Recent
      progress in studies of retromer have identified new retromer-interacting
      proteins, including the WASH complex and cargo such as the Wntless/MIG-14
      protein, which now extends the role of retromer beyond the endosome-to-Golgi
      pathway and has revealed that retromer is required for aspects of endosome-to
      plasma membrane sorting and regulation of signalling events. The interactions
      between the retromer complex and other macromolecular protein complexes now show
      how endosomal protein sorting is coordinated with actin assembly and movement
      along microtubules, and place retromer squarely at the centre of a complex set of
      protein machinery that governs endosomal protein sorting. Dysregulation of
      retromer-mediated endosomal protein sorting leads to various pathologies,
      including neurodegenerative diseases such as Alzheimer disease and spastic
      paraplegia and the mechanisms underlying these pathologies are starting to be
      understood. In this Commentary, I will highlight recent advances in the
      understanding of retromer-mediated endosomal protein sorting and discuss how
      retromer contributes to a diverse set of physiological processes.

PMID- 23148302
TI  - Technical note: A general transformation formula for interval traits connected
      with reproduction in pigs.
AB  - A general transformation formula is presented for interval traits in pigs, such
      as weaning-to-first-service interval or farrowing interval. In the logarithmic
      transformation, only observations that are greater than the median of the trait
      as originally recorded are transformed. The transformation considerably reduces
      the skewness and kurtosis of the trait so that the distribution of transformed
      data approaches normality. In analysis of >12,000 records for weaning-to-first
      service interval and >9,000 records for farrowing interval, heritability
      estimates for the transformed data were greater than for the data as recorded.
      Therefore, selection on the transformed trait should be more effective than
      selection on the original trait. The transformation formula is likely to be
      appropriate for other livestock species and traits.

PMID- 23148301
TI  - The costs and potential savings of telemedicine for acute care neonatal
      consultation: preliminary findings.
AB  - Telemedicine was used as a substitute for the telephone (usual care) for some
      acute care consultations from nurseries at four peripheral hospitals in
      Queensland. Over a 12-month study period, there were 19 cases of neonatal
      teleconsultation. Five (26%) cases of avoided infant transport were confirmed by
      independent assessment, four of which were avoided helicopter retrievals. We
      conducted two analyses. In the first, the actual costs of providing telemedicine
      at the study sites were compared with the actual savings associated with
      confirmed avoided infant transport and nursery costs. There was a net saving to
      the health system of 54,400 Australian Dollars (AUD) associated with the use of
      telemedicine over the 12-month period. In the second analysis, we estimated the
      potential savings that might have been achieved if telemedicine had been used for
      all retrieval consultations from the study sites. The total projected costs were
      AUD 64,969 while the projected savings were AUD 271,042, i.e. a projected net
      saving to the health system of AUD 206,073 through the use of telemedicine. A
      sensitivity analysis suggested that the threshold proportion of retrievals needed
      to generate telemedicine-related savings under the study conditions was 5%. The
      findings suggest that from the health-service perspective, the use of
      telemedicine for acute care neonatal consultation has substantial economic
      benefits.

PMID- 23148303
TI  - Effects of feeding fiber-fermenting bacteria to pigs on nutrient digestion, fecal
      output, and plasma energy metabolites.
AB  - Inclusion of feedstuffs with higher plant cell wall (fiber) content in swine
      diets has increased in recent years due to greater availability and lower cost,
      especially coproduct feeds, such as corn distillers dried grains with soluble
      (DDGS). Limitations of feeding higher fiber diets include increased fecal output,
      which can exceed manure storage volumes, and decreased energy density, which can
      decrease growth performance; dietary treatments that ameliorate these limitations
      would benefit pork producers. Grower pigs (n = 48; 61.1 kg initial BW) were used
      to establish the effects of supplementation of fiber-fermenting bacteria in a 2 *
      4 factorial, consisting of 2 diets (standard and high fiber) and 4 bacterial
      treatments (A, no bacteria; and B, C, and D bacterial supplements). Increased
      fiber came from inclusion of soybean hulls (10%) and corn DDGS (20%) in the diet.
      The 3 bacterial supplements (all Bacteroides strains) were isolated from fecal
      enrichment cultures and selected for their fiber-fermenting capacity. The high
      fiber diet increased fecal output, blood cholesterol, and triglyceride
      concentrations, and digestibility of NDF, ADF, and S; CP digestibility decreased
      (P <= 0.10). The improved fiber digestibility and altered energy status of pigs
      fed the high fiber diet was primarily due to fermentation of soybean hulls,
      resulting in increased short-chain fatty acid production and absorption, and
      decreased dietary starch content. Overall, pigs fed the bacterial treatments had
      only increased blood cholesterol concentrations (P = 0.10). When individual
      bacterial treatments were compared, pigs fed Bacteria B had decreased fecal
      output (P <= 0.10) and both blood glucose and cholesterol concentrations were
      increased (P <= 0.10) compared with the other 3 treatments, indicating an
      improved energy status. Pigs fed Bacteria B increased both CP and ADF (P <=
      0.10), and tended (P = 0.16) to have increased NDF digestibilities compared with
      pigs fed no bacteria (Treatment A), whereas pigs fed the other 2 bacterial
      treatments did not differ from pigs fed Bacteria B for nutrient digestibility.
      Both had similar fecal outputs to pigs fed no bacteria. This is the first report
      of reduction in fecal output and increased fiber digestibility with pigs fed live
      bacteria. Successful application of this bacterial treatment could result in
      improved pig performance and decreased manure volumes, both of which would
      improve profitability of producers.

PMID- 23148304
TI  - Effects of delayed steroid implanting on health, performance, and carcass quality
      in high health risk, auction market-sourced feedlot steers.
AB  - Auction-derived feeder calves (n = 1,601; initial BW = 273.5 +/- 4.7 kg) were
      used to examine effects of delayed administration of the initial steroid implant
      on health, performance, and carcass characteristics of feedlot cattle. Steers
      were procured from multiple auction markets in the southeastern United States and
      shipped to a central Kansas feedyard over a 6-wk period from December 2009 to
      January 2010. Steers were rested overnight before processing, then were randomly
      assigned, within arrival block, to 1 of 2 treatments: 1) implanted with Revalor
      XS (40 mg estradiol and 200 mg trenbolone acetate) immediately upon arrival or 2)
      implanted with Revalor-XS 45 d postarrival. Cattle were weighed by pen using a
      group scale immediately after processing of each block. Feed deliveries were
      measured using load cells on feed trucks and recorded daily. Cattle were
      evaluated daily for morbidity and mortality by feedyard health personnel. Sick or
      injured cattle were removed from the home pen for further diagnosis and
      treatment. Individual animal health data were obtained and recorded daily. Final
      BW was calculated by dividing HCW by average dressing percent of the pen. Carcass
      data (quality grade and yield grade) were obtained by USDA personnel; presence of
      lung lesions, pleural adhesions, and liver abscesses were evaluated by trained
      university personnel. Delaying the initial implant tended to reduce morbidity
      (24.7 vs. 28.5%; P = 0.13) and reduced the percentage of animals requiring early
      salvage harvest due to chronic, nonresponsive respiratory disease (1.8 vs. 3.3%;
      P = 0.02). However, there were no effects of timing of implant administration (P
      >= 0.31) on rates of retreatment, mortality, lung lesions, or pleural adhesions.
      Implanting immediately upon feedlot arrival resulted in no effect on ADG or feed
      conversion (P >= 0.30). Cattle implanted upon arrival had numerically greater HCW
      and yield grade vs. cattle implanted on d 45; however, these differences were not
      significant (P >= 0.16). Delaying the initial implant 45 d did not greatly
      influence animal health, performance parameters, or carcass characteristics in
      feeder calves at high risk of developing bovine respiratory disease.

PMID- 23148305
TI  - Inactivation of tankyrases reduces experimental fibrosis by inhibiting canonical
      Wnt signalling.
AB  - OBJECTIVES: Canonical Wnt signalling has recently emerged as a key mediator of
      fibroblast activation and tissue fibrosis in systemic sclerosis. Here, we
      investigated tankyrases as novel molecular targets for inhibition of canonical
      Wnt signalling in fibrotic diseases. METHODS: The antifibrotic effects of the
      tankyrase inhibitor XAV-939 or of siRNA-mediated knockdown of tankyrases were
      evaluated in the mouse models of bleomycin-induced dermal fibrosis and in
      experimental fibrosis induced by adenoviral overexpression of a constitutively
      active TGF-beta receptor I (Ad-TBRI). RESULTS: Inactivation of tankyrases
      prevented the activation of canonical Wnt signalling in experimental fibrosis and
      reduced the nuclear accumulation of beta-catenin and the mRNA levels of the
      target gene c-myc. Treatment with XAV-939 or siRNA-mediated knockdown of
      tankyrases in the skin effectively reduced bleomycin-induced dermal thickening,
      differentiation of resting fibroblasts into myofibroblasts and accumulation of
      collagen. Potent antifibrotic effects were also observed in Ad-TBRI driven skin
      fibrosis. Inhibition of tankyrases was not limited by local or systemic toxicity.
      CONCLUSIONS: Inactivation of tankyrases effectively abrogated the activation of
      canonical Wnt signalling and demonstrated potent antifibrotic effects in well
      tolerated doses. Thus, tankyrases might be candidates for targeted therapies in
      fibrotic diseases.

PMID- 23148306
TI  - TLR4 as receptor for HMGB1 induced muscle dysfunction in myositis.
AB  - OBJECTIVES: Polymyositis and dermatomyositis are characterised by muscle weakness
      and fatigue even in patients with normal muscle histology via unresolved
      pathogenic mechanisms. In this study, we investigated the mechanisms by which
      high mobility group box protein 1 (HMGB1) acts to accelerate muscle fatigue
      development. METHODS: Intact single fibres were dissociated from flexor digitorum
      brevis (FDB) of wild type, receptor for advanced glycation endproduct (RAGE)
      knockout and toll like receptor 4 (TLR4) knockout mice and cultured in the
      absence or presence of recombinant HMGB1. A decrease in sarcoplasmic reticulum
      Ca(2+) release during a series of 300 tetanic contractions, which reflects the
      development of muscle fatigue, was determined by measuring myoplasmic free
      tetanic Ca(2+). TLR4 and major histocompatibility complex (MHC)-class I
      expression in mouse FDB fibres were investigated by immunofluorescence and
      confocal microscopy. Immunohistochemistry was used to investigate TLR4, MHC-class
      I and myosin heavy chain expression in muscle fibres of patients. RESULTS: Our
      results demonstrate that TLR4 is expressed in human and mouse skeletal muscle
      fibres, and coexpressed with MHC-class I in muscle fibres of patients with
      myositis. Furthermore, we show that HMGB1 acts via TLR4 but not RAGE to
      accelerate muscle fatigue and to induce MHC-class I expression in vitro. In order
      to bind and signal via TLR4, HMGB1 must have a reduced cysteine 106 and a
      disulphide linkage between cysteine 23 and 45. CONCLUSIONS: The HMGB1-TLR4
      pathway may play an important role in causing muscle fatigue in patients with
      polymyositis or dermatomyositis and thus is a potential novel target for future
      therapy.

PMID- 23148307
TI  - Successful long-term triple disease control by ustekinumab in a patient with
      Behcet's disease, psoriasis and hidradenitis suppurativa.

PMID- 23148308
TI  - Serum hepcidin level is not an independent surrogate biomarker of disease
      activity or of radiographic progression in rheumatoid arthritis: results from the
      ESPOIR cohort.

PMID- 23148309
TI  - Long-term work disability in patients with psoriatic arthritis treated with anti
      tumour necrosis factor: a population-based regional Swedish cohort study.
AB  - OBJECTIVE: To study long-term work disability before and after tumour necrosis
      factor (TNF)-antagonist therapy in patients with psoriatic arthritis (PsA).
      METHODS: Using the population-based South Swedish Arthritis Treatment Group
      Register, we identified 191 patients with PsA (median age 43 years, range 18-58
      years, 54% men), who between January 2003 and December 2007 started treatment
      with adalimumab, etanercept or infliximab. We linked data to the Swedish Social
      Insurance Agency and calculated the proportion of work disability in 30-day
      intervals from 12 months before the start of treatment until 3 years after. For
      each patient with PsA we randomly selected four matched reference subjects from
      the general population. RESULTS: At treatment initiation 67% of the patients with
      PsA were work disabled-that is, either on sick leave (41.5%) or receiving a
      disability pension (25.3%). Patients sustaining treatment were, on average, work
      disabled 12.5 days a month at treatment initiation declining to 10.6 days a month
      after 3 years of treatment. Patients for whom the first treatment course failed
      were work disabled 16.5 days at treatment start decreasing to 15.6 days after 3
      years. The background population were 2.5 days and 3.0 days off work each month,
      respectively. Regression modelling identified prior work disability status, anti
      TNF treatment failure, higher age, female gender and longer disease duration as
      significant predictors of working disability. CONCLUSIONS: There was a decline in
      net work disability after initiation of anti-TNF treatment in patients with PsA.
      Patients withdrawing from treatment had a 50% increased risk of being work
      disabled. Prior work disability, higher age, female gender and longer disease
      duration were also associated with long-term work disability.

PMID- 23148310
TI  - Good medium-term efficacy of tocilizumab in DMARD and anti-TNF-alpha therapy
      resistant reactive amyloidosis.

PMID- 23148311
TI  - Postnatal depression in mothers bringing infants to the emergency department.
AB  - OBJECTIVE: To determine the prevalence of postnatal depression (PND) in mothers
      of young infants presenting to the emergency department (ED). DESIGN, SETTING AND
      PARTICIPANTS: Prospective observational study of the prevalence of PND in mothers
      of infants aged 14 days to 6 months presenting with non-time-critical conditions
      to the ED of a large tertiary paediatric hospital. MAIN OUTCOME MEASURES: We
      assessed PND by applying a self-administered validated screening tool, the
      Edinburgh Postnatal Depression Scale (EPDS). Mothers of patients were approached
      before clinician consultation when a social worker was available on site. EPDS
      scores of 13 and above were considered 'positive'. Univariate analysis was used
      to determine associations with demographic, maternal and child factors. RESULTS:
      236 mothers were approached; 200 consented to participate in the study. Thirty
      two mothers screened positively, with a prevalence rate of 16% (95% CI 11.2% to
      21.8%). A positive screen was most strongly associated with history of depression
      (relative risk (RR) 4.8, 95% CI 2.3 to 10.1). Other associations were with single
      parent status (RR 2.5, 95% CI 1.1 to 5.4), Indigenous status (4.4, 95% CI 1.8 to
      10.4) and 'crying baby' as the presenting problem (RR 2.9, 95% CI 1.4 to 6.2).
      Fifty-three per cent of mothers had not completed a PND screen before coming to
      the ED. CONCLUSIONS: Mothers of young infants coming to the ED regardless of
      infant's presenting complaint have a high prevalence of PND determined using the
      EPDS. Many mothers were not screened for PND before coming to the ED. Clinical
      staff need to be aware of the condition, incorporate appropriate questioning into
      the consultation, and refer mothers to support services if necessary.

PMID- 23148312
TI  - Glossal hamartoma in tuberous sclerosis.

PMID- 23148313
TI  - Catch-up growth in children born growth restricted to mothers with hypertensive
      disorders of pregnancy.
AB  - BACKGROUND: In preterm hypertensive disorders of pregnancy, fetal growth
      restriction (FGR) occurs frequently. The timing and severity of FGR impacts
      childhood growth and is associated with metabolic changes later in life. AIM: To
      examine growth and the impact of FGR in early childhood. DESIGN: Prospective
      cohort study. PARTICIPANTS: Children (n=135) born to mothers who were admitted
      before 34 weeks' gestational age with a severe hypertensive disorder of
      pregnancy. OUTCOME MEASURES: Height, weight, body mass index (BMI), head
      circumference (HC), SD scores (SDS) at 3 months, and 1 and 4.5 years of age, and
      complete catch-up growth (height SDS-target height SDS >-1.6). RESULTS: Growth
      scores were lower compared to Dutch growth curves, except for BMI at 3 months and
      girls' HC at all ages. Mean height SDS increased over time from -1.4 to -0.5 at
      4.5 years, with 94% having complete catch-up growth. Mean BMI SDS decreased from 
      0.2 at 3 months to -1.0 at 1 year, and was -0.8 at age 4.5. Mean HC SDS was
      stable over time and -0.3 at 4.5 years. The customised birth weight ratio, as a
      measure of the degree of FGR, was related to all growth SDS at 4.5 years, while
      gestational age at birth was not. CONCLUSIONS: Although the majority of children
      born growth restricted had catch-up growth of height within the normal range at
      4.5 years of age, they were smaller, but especially lighter compared to Dutch
      growth charts. The degree of FGR was associated with all growth outcomes.

PMID- 23148314
TI  - Vitamin K deficiency bleeding after NICE guidance and withdrawal of Konakion
      Neonatal: British Paediatric Surveillance Unit study, 2006-2008.
AB  - OBJECTIVE: To survey vitamin K deficiency bleeding (VKDB) and document vitamin K
      (VK) prophylaxis practice, and compare with findings predating withdrawal of
      Konakion Neonatal and guidance from the National Institute of Health and Clinical
      Excellence (NICE), both occurring in 2006. DESIGN: Two-year surveillance of VKDB
      (2006-2008) using British Paediatric Surveillance Unit methodology. Postal
      questionnaire to consultant-led maternity units. SETTING: UK and Irish Republic.
      PATIENTS: All newborns and infants under 6 months with suspected VKDB. MAIN
      OUTCOME MEASURES: VKDB incidence and predisposing factors, VK prophylaxis
      recommended/received. RESULTS: Eleven cases of VKDB were found: six (55%) babies
      received no VK prophylaxis, in five (45.5%) because parents withheld consent;
      three (27.5%) babies with late VKDB received intramuscular (IM) Konakion MM (two
      had biliary atresia, and one was delivered preterm); two (18%) babies received
      incomplete oral prophylaxis. Nine babies (82%) were breast fed. Three (27%)
      babies had liver disease; four (36%), including all those with liver disease,
      were jaundiced at presentation after 21 days. Four (36%) babies had intracranial
      haemorrhage, two probably suffering long-term morbidity. VK prophylaxis practice
      was defined in 236 (100%) units. All units recommended prophylaxis for every
      newborn: 169 (72%) IM, 19 (8%) oral, and 48 (20%) offered parental choice. All
      units that recommended IM prophylaxis used Konakion MM. Oral prophylaxis always
      involved multidose regimens for breastfed babies; 61 (91%) units used Konakion
      MM, and six (9%) used unlicensed products suitable for administration by parents.
      CONCLUSIONS: IM Konakion MM is efficacious, but parents withholding consent for
      recommended IM prophylaxis reduces effectiveness. Reappraisal of NICE guidance
      would be appropriate. Prolonged jaundice demands investigation. Late VKDB
      occasionally occurs after IM prophylaxis.

PMID- 23148315
TI  - Evolutionarily conserved differences in pallial and thalamic short-term synaptic
      plasticity in striatum.
AB  - The striatum of the basal ganglia is conserved throughout the vertebrate phylum.
      Tracing studies in lamprey have shown that its afferent inputs are organized in a
      manner similar to that of mammals. The main inputs arise from the thalamus (Th)
      and lateral pallium (LPal; the homologue of cortex) that represents the two
      principal excitatory glutamatergic inputs in mammals. The aim here was to
      characterize the pharmacology and synaptic dynamics of afferent fibres from the
      LPal and Th onto identified striatal neurons to understand the processing taking
      place in the lamprey striatum. We used whole-cell current-clamp recordings in
      acute slices of striatum with preserved fibres from the Th and LPal, as well as
      tract tracing and immunohistochemistry. We show that the Th and LPal produce
      monosynaptic excitatory glutamatergic input through NMDA and AMPA receptors. The
      synaptic input from the LPal displayed short-term facilitation, unlike the Th
      input that instead displayed strong short-term synaptic depression. There was
      also an activity-dependent recruitment of intrastriatal oligosynaptic inhibition
      from both inputs. These results indicate that the two principal inputs undergo
      different activity-dependent short-term synaptic plasticity in the lamprey
      striatum. The difference observed between Th and LPal (cortical) input is also
      observed in mammals, suggesting a conserved trait throughout vertebrate
      evolution.

PMID- 23148316
TI  - Dampened dopamine-mediated neuromodulation in prefrontal cortex of fragile X
      mice.
AB  - Fragile X syndrome (FXS) is the most common form of inheritable mental
      retardation caused by transcriptional silencing of the Fmr1 gene resulting in the
      absence of fragile X mental retardation protein (FMRP). The role of this protein
      in neurons is complex and its absence gives rise to diverse alterations in
      neuronal function leading to neurological disorders including mental retardation,
      hyperactivity, cognitive impairment, obsessive-compulsive behaviour, seizure
      activity and autism. FMRP regulates mRNA translation at dendritic spines where
      synapses are formed, and thus the lack of FMRP can lead to disruptions in
      synaptic transmission and plasticity. Many of these neurological deficits in FXS
      probably involve the prefrontal cortex, and in this study, we have focused on
      modulatory actions of dopamine in the medial prefrontal cortex. Our data indicate
      that dopamine produces a long-lasting enhancement of evoked inhibitory
      postsynaptic currents (IPSCs) mediated by D1-type receptors seen in wild-type
      mice; however, such enhancement is absent in the Fmr1 knock-out (Fmr1 KO) mice.
      The facilitation of IPSCs produced by direct cAMP stimulation was unaffected in
      Fmr1 KO, but D1 receptor levels were reduced in these animals. Our results show
      significant disruption of dopaminergic modulation of synaptic transmission in the
      Fmr1 KO mice and this alteration in inhibitory activity may provide insight into
      potential targets for the rescue of deficits associated with FXS.

PMID- 23148317
TI  - Functional expression of SK channels in murine detrusor PDGFR+ cells.
AB  - We sought to characterize molecular expression and ionic conductances in a novel
      population of interstitial cells (PDGFRalpha(+) cells) in murine bladder to
      determine how these cells might participate in regulation of detrusor
      excitability. PDGFRalpha(+) cells and smooth muscle cells (SMCs) were isolated
      from detrusor muscles of PDGFRalpha(+)/eGFP and smMHC/Cre/eGFP mice and sorted by
      FACS. PDGFRalpha(+) cells were highly enriched in Pdgfra (12 fold vs. unsorted
      cell) and minimally positive for Mhc (SMC marker), Kit (ICC marker) and Pgp9.5
      (neuronal marker). SK3 was dominantly expressed in PDGFRalpha(+) cells in
      comparison to SMCs. alphaSlo (BK marker) was more highly expressed in SMCs. SK3
      protein was observed in PDGFRalpha(+) cells by immunohistochemistry but could not
      be resolved in SMCs. Depolarization evoked voltage-dependent Ca(2+) currents in
      SMCs, but inward current conductances were not activated in PDGFRalpha(+) cells
      under the same conditions. PDGFRalpha(+) cells displayed spontaneous transient
      outward currents (STOCs) at potentials positive to -60 mV that were inhibited by
      apamin. SK channel modulators, CyPPA and SKA-31, induced significant
      hyperpolarization of PDGFRalpha(+) cells and activated SK currents under voltage
      clamp. Similar responses were not resolved in SMCs at physiological potentials.
      Single channel measurements confirmed the presence of functional SK3 channels
      (i.e. single channel conductance of 10 pS and sensitivity to intracellular
      Ca(2+)) in PDGFRalpha(+) cells. The apamin-sensitive stabilizing factor
      regulating detrusor excitability is likely to be due to the expression of SK3
      channels in PDGFRalpha(+) cells because SK agonists failed to elicit resolvable
      currents and hyperpolarization in SMCs at physiological potentials.

PMID- 23148318
TI  - Ca2+-dependent proteolysis of junctophilin-1 and junctophilin-2 in skeletal and
      cardiac muscle.
AB  - Excessive increases in intracellular [Ca(2+)] in skeletal muscle fibres cause
      failure of excitation-contraction coupling by disrupting communication between
      the dihydropyridine receptors in the transverse tubular system and the Ca(2+)
      release channels (RyRs) in the sarcoplasmic reticulum (SR), but the exact
      mechanism is unknown. Previous work suggested a possible role of Ca(2+)-dependent
      proteolysis in this uncoupling process but found no proteolysis of the
      dihydropyridine receptors, RyRs or triadin. Junctophilin-1 (JP1; ~90 kDa)
      stabilizes close apposition of the transverse tubular system and SR membranes in
      adult skeletal muscle; its C-terminal end is embedded in the SR and its N
      terminal associates with the transverse tubular system membrane. Exposure of
      skeletal muscle homogenates to precisely set [Ca(2+)] revealed that JP1 undergoes
      Ca(2+)-dependent proteolysis over the physiological [Ca(2+)] range in tandem with
      autolytic activation of endogenous MU-calpain. Cleavage of JP1 occurs close to
      the C-terminal, yielding a ~75 kDa diffusible fragment and a fixed ~15 kDa
      fragment. Depolarization-induced force responses in rat skinned fibres were
      abolished following 1 min exposure to 40 MUm Ca(2+), with accompanying loss of
      full-length JP1. Supraphysiological stimulation of rat skeletal muscle in vitro
      by repeated tetanic stimulation in 30 mm caffeine also produced marked
      proteolysis of JP1 (and not RyR1). In dystrophic mdx mice, JP1 proteolysis is
      seen in limb muscles at 4 and not at 10 weeks of age. Junctophilin-2 in cardiac
      and skeletal muscle also undergoes Ca(2+)-dependent proteolysis, and junctophilin
      2 levels are reduced following cardiac ischaemia-reperfusion. Junctophilin
      proteolysis may contribute to skeletal muscle weakness and cardiac dysfunction in
      a range of circumstances.

PMID- 23148319
TI  - Chronic exposure of neonatal rat adrenomedullary chromaffin cells to opioids in
      vitro blunts both hypoxia and hypercapnia chemosensitivity.
AB  - At birth, rat adrenomedullary chromaffin cells (AMCs) respond directly to
      asphyxial stressors such as hypoxia and hypercapnia by triggering catecholamine
      secretion, which is critical for proper transition to extrauterine life. These
      non-neurogenic responses are suppressed postnatally in parallel with the
      development of splanchnic innervation, and reappear following denervation of the
      adult adrenal gland. To test whether neural factors released from the splanchnic
      nerve may regulate AMC chemosensitivity, we previously showed that nicotinic
      agonists in utero and in vitro suppressed hypoxia, but not hypercapnia,
      sensitivity. Here, we considered the potential role of opiate peptides which are
      also released from the splanchnic nerve and act via postsynaptic MU-, delta- and 
      opioid receptors. Treatment of neonatal rat AMC cultures for ~1 week with MU-
      and/or delta- (but not ) opioid agonists (2 MUm) led to a marked suppression of
      both hypoxia and hypercapnia sensitivity, as measured by K(+) current inhibition
      and membrane depolarization; co-incubation with naloxone prevented the effects of
      combined opioids. The suppression of hypoxia sensitivity was attributable to
      upregulation of K(ATP) current density and the K(ATP) channel subunit Kir6.2, and
      was reversed by the K(ATP) channel blocker, glibenclamide. By contrast,
      suppression of hypercapnia sensitivity was associated with down-regulation of two
      key mediators of CO(2) sensing, i.e. carbonic anhydrase I and II. Collectively,
      these studies point to a novel role for opioid receptor signalling in the
      developmental regulation of chromaffin cell chemosensitivity, and suggest that
      prenatal exposure to opioid drugs could lead to impaired arousal responses in the
      neonate.

PMID- 23148320
TI  - Dynamic measurement of the calcium buffering properties of the sarcoplasmic
      reticulum in mouse skeletal muscle.
AB  - The buffering power, B, of the sarcoplasmic reticulum (SR), ratio of the changes
      in total and free [Ca(2+)], was determined in fast-twitch mouse muscle cells
      subjected to depleting membrane depolarization. Changes in total SR [Ca(2+)] were
      measured integrating Ca(2+) release flux, determined with a cytosolic [Ca(2+)]
      monitor. Free [Ca(2+)](SR) was measured using the cameleon D4cpv-Casq1. In 34
      wild-type (WT) cells average B during the depolarization (ON phase) was 157 (SEM
      26), implying that of 157 ions released, 156 were bound inside the SR. B was
      significantly greater when BAPTA, which increases release flux, was present in
      the cytosol. B was greater early in the pulse - when flux was greatest - than at
      its end, and greater in the ON than in the OFF. In 29 Casq1-null cells, B was 40
      (3.6). The difference suggests that 75% of the releasable calcium is normally
      bound to calsequestrin. In the nulls the difference in B between ON and OFF was
      less than in the WT but still significant. This difference and the associated
      decay in B during the ON were not artifacts of a slow SR monitor, as they were
      also found in the WT when [Ca(2+)](SR) was tracked with the fast dye fluo-5N. The
      calcium buffering power, binding capacity and non-linear binding properties of
      the SR measured here could be accounted for by calsequestrin at the concentration
      present in mammalian muscle, provided that its properties were substantially
      different from those found in solution. Its affinity should be higher, or K(D)
      lower than the conventionally accepted 1 mm; its cooperativity (n in a Hill fit)
      should be higher and the stoichiometry of binding should be at the higher end of
      the values derived in solution. The reduction in B during release might reflect
      changes in calsequestrin conformation upon calcium loss.

PMID- 23148322
TI  - Nonsense-mediated mRNA decay: from mechanistic insights to impacts on human
      health.
AB  - Cells are able to recognize and degrade aberrant transcripts in order to self
      protect from potentially toxic proteins. Various pathways detect aberrant RNAs in
      the cytoplasm and are dependent on translation. One of these pathways is the
      nonsense-mediated RNA decay (NMD). NMD is a surveillance mechanism that degrades
      transcripts containing nonsense mutations, preventing the translation of possibly
      harmful truncated proteins. For example, the degradation of a nonsense harming
      beta-globin allele renders normal phenotypes. On the other hand, regulating NMD
      is also important in those cases when the produced aberrant protein is better
      than having no protein, as it has been shown for cystic fibrosis. These findings
      reflect the important role for NMD in human health. In addition, NMD controls the
      levels of physiologic transcripts, which defines this pathway as a novel gene
      expression regulator, with huge impact on homeostasis, cell growth and
      development. While the mechanistic details of NMD are being gradually understood,
      the physiological role of this RNA surveillance pathway still remains largely
      unknown. This is a brief and simplified review on various aspects of NMD, such as
      the nature of the NMD targets, the mechanism of target degradation and the links
      between NMD and cell growth, animal development and diseases.

PMID- 23148323
TI  - Processing of plant microRNA precursors.
AB  - MicroRNAs are endogenous small RNAs known to be key regulators of gene expression
      in animals and plants. They are defined by their specific biogenesis which
      involves the precise excision from an imperfect fold-back precursor. These
      precursors contain structural determinants required for their correct processing.
      Still, there are significant differences in the biogenesis and activities of
      plant and animal microRNAs. This review summarizes diverse aspects of precursor
      processing in plants, contrasting them to their animal counterparts.

PMID- 23148324
TI  - State-of-the-art technology in modern computer-aided drug design.
AB  - The quest for small drug-like compounds that selectively inhibit the function of
      biological targets has always been a major focus in the pharmaceutical industry
      and in academia as well. High-throughput screening of compound libraries requires
      time, cost and resources. Therefore, the use of alternative methods is necessary
      for facilitating lead discovery. Computational techniques that dock small
      molecules into macromolecular targets and predict the affinity and activity of
      the small molecule are widely used in drug design and discovery, and have become
      an integral part of the industrial and academic research. In this review, we
      present an overview of some state-of-the-art technologies in modern drug design
      that have been developed for expediting the search for novel drug candidates. 

PMID- 23148321
TI  - Failure of action potential propagation in sensory neurons: mechanisms and loss
      of afferent filtering in C-type units after painful nerve injury.
AB  - The T-junction of sensory neurons in the dorsal root ganglion (DRG) is a
      potential impediment to action potential (AP) propagation towards the CNS. Using
      intracellular recordings from rat DRG neuronal somata during stimulation of the
      dorsal root, we determined that the maximal rate at which all of 20 APs in a
      train could successfully transit the T-junction (following frequency) was lowest
      in C-type units, followed by A-type units with inflected descending limbs of the
      AP, and highest in A-type units without inflections. In C-type units, following
      frequency was slower than the rate at which AP trains could be produced in either
      dorsal root axonal segments or in the soma alone, indicating that the T-junction
      is a site that acts as a low-pass filter for AP propagation. Following frequency
      was slower for a train of 20 APs than for two, indicating that a cumulative
      process leads to propagation failure. Propagation failure was accompanied by
      diminished somatic membrane input resistance, and was enhanced when Ca(2+)
      sensitive K(+) currents were augmented or when Ca(2+)-sensitive Cl(-) currents
      were blocked. After peripheral nerve injury, following frequencies were increased
      in axotomized C-type neurons and decreased in axotomized non-inflected A-type
      neurons. These findings reveal that the T-junction in sensory neurons is a
      regulator of afferent impulse traffic. Diminished filtering of AP trains at the T
      junction of C-type neurons with axotomized peripheral processes could enhance the
      transmission of activity that is ectopically triggered in a neuroma or the
      neuronal soma, possibly contributing to pain generation.

PMID- 23148325
TI  - Sport injuries and illnesses during the first Winter Youth Olympic Games 2012 in
      Innsbruck, Austria.
AB  - BACKGROUND: Data on the injury and illness risk among young elite athletes are of
      utmost importance, because injuries and illnesses can counter the beneficial
      effects of sports participation at a young age, if children or adolescents are
      unable to continue to participate because of residual effects of injury or
      chronic illness. OBJECTIVE: To analyse the frequencies and characteristics of
      injuries and illnesses during the 2012 Innsbruck Winter Youth Olympic Games
      (IYOG). METHODS: We employed the International Olympic Committee (IOC) injury
      surveillance system for multisport events, which was updated for the Winter
      Olympic Games in Vancouver 2010. All National Olympic Committees (NOCs) were
      asked to report the daily occurrence (or non-occurrence) of newly sustained
      injuries and illnesses on a standardised reporting form. In addition, information
      on athletes treated for injuries and illnesses by the Local Organizing Committee
      medical services was retrieved from the medical centre at the Youth Olympic
      Village and from the University hospital in Innsbruck. RESULTS: Among the 1021
      registered athletes (45% women, 55% men) from 69 NOCs, a total of 111 injuries
      and 86 illnesses, during the IYOG, were reported, resulting in an incidence of
      108.7 injuries and 84.2 illnesses per 1000 registered athletes, respectively.
      Injury frequency was highest in skiing in the halfpipe (44%) and snowboarding
      (halfpipe and slope style: 35%), followed by ski cross (17%), ice hockey (15%),
      alpine skiing (14%) and figure skating (12%), taking into account the respective
      number of participating athletes. Knee, pelvis, head, lower back and shoulders
      were the most common injury locations. About 60% of injuries occurred in
      competition and about 40% in training, respectively. In total, 32% of the
      injuries resulted in an absence from training or competition. With regard to
      illnesses, 11% of women and 6% of men suffered from an illness (RR=1.84 (95% CI
      1.21 to 2.78), p=0.003). The respiratory system was affected most often (61%).
      CONCLUSIONS: Eleven per cent of the athletes suffered from an injury and 9% from
      illnesses, during the IYOG. The presented data constitute the basis for future
      analyses of injury mechanisms and associated risk factors in Olympic Winter
      sports, which, in turn, will be essential to develop and implement effective
      preventive strategies for young elite winter-sport athletes.

PMID- 23148326
TI  - Quality of life, coach behaviour and competitive anxiety in Winter Youth Olympic
      Games participants.
AB  - BACKGROUND: To ensure the highest technical performance, speed, safety, excellent
      control and to improve competitive performance, a successful regulation of
      competitive anxiety is necessary. Therefore, it seems crucial to identify factors
      influencing competitive anxiety of adolescent athletes. Research suggests that
      people reporting high quality of life are more capable to cope with stressful and
      challenging situations than others. The aim of this study was to investigate the
      impact of quality of life, the involvement of parents in sports career and
      coach's leadership behaviour on competitive anxiety in Winter Youth Olympic Games
      participants. METHODS: During the first Winter Youth Olympic Games 2012 in
      Innsbruck/Austria, 662 (316 women) participants completed questionnaires and
      single items to assess quality of life, coach's leadership behaviour, parental
      involvement in sports career and competitive anxiety. RESULTS: Multiple
      regression analysis revealed positive influences of high quality of life and
      useful coach instruction on competitive anxiety. CONCLUSIONS: The relationship
      between quality of life, coach behaviour and competitive anxiety in young elite
      athletes competing at the first Winter Youth Olympic Games should be considered
      in long-term programmes for reducing competitive stress.

PMID- 23148327
TI  - Ensuring the health of future populations.

PMID- 23148328
TI  - CABG not PCI for adults with diabetes.

PMID- 23148329
TI  - Accelerating suicide rate linked to economic downturn in the US.

PMID- 23148330
TI  - Aspirin prevents recurrent venous thromboembolism.

PMID- 23148331
TI  - Junior doctors take heart: you do everything as well as we did.

PMID- 23148332
TI  - Roche should be sued to release data on oseltamivir, says Cochrane leader.

PMID- 23148333
TI  - Make or break for the Global Fund?

PMID- 23148334
TI  - Germany repeals ?10 quarterly charge for visiting the doctor.

PMID- 23148335
TI  - How India can provide healthcare for all.

PMID- 23148336
TI  - Correction.

PMID- 23148337
TI  - Differences in risk factors for voluntary early retirement and disability
      pension: a 15-year follow-up in a cohort of nurses' aides.
AB  - OBJECTIVE: To estimate the extent of early retirement and to examine risk factors
      for voluntary early retirement and disability pension in a cohort of nurses'
      aides. DESIGN: Register study including baseline questionnaire and register data
      covering all transfer incomes from 1991 to 2008 in a cohort of nurses' aides
      established in 1993 with a follow-up period of 15 years. SETTING: Nurses' aides
      working in nursery homes, homecare or hospitals. PARTICIPANTS: 3332 gainfully
      employed nurses' aides at the time of inclusion in the study. OUTCOME: Disability
      pension or early voluntary retirement. RESULTS: 16.2% of the population was
      granted disability pension and 27.1% entered early voluntary retirement in the
      follow-up period representing 11 186 lost working years with a direct cost in
      transfer payment amounting about ?410 million. Health-related risk factors for
      disability pension was long-lasting low-back pain (HR 2.27(95% CI 1.55 to 3.34),
      sick leave because of upper-extremity disorders (HR 2.18 (95% CI 1.08 to 2.11),
      and inflammatory rheumatic disease (HR 2.42 (95% CI 1.67 to 3.52)). Of non-health
      related factors, low education, workers compensation case, evening work and high
      rated perceived exertion at work all were minor risk factors for disability
      pension. The primary risk factor for early voluntary retirement was low education
      (HR 3.19 (95% CI 2.65 to 3.85)). CONCLUSIONS: 43.3% of nurses' aides gainfully
      employed in 1993 retired before due time during the follow-up period. Work
      related factors at baseline only seemed to have a minor prognostic role. Risk
      factors for disability pension were mainly health-related factors, whereas
      economical factors seemed to influence the decision to choose early voluntary
      retirement. The number of persons and the amount of lost working years
      underscores the need of a more active counselling towards maintaining employment
      especially among those with persistent musculoskeletal disorders.

PMID- 23148338
TI  - Assessing the limitations of the existing physician directory for measuring
      electronic health record (EHR) adoption rates among physicians in Connecticut,
      USA: cross-sectional study.
AB  - OBJECTIVE: To assess the limitations of the existing physician directory in
      measuring electronic health record adoption rates among a cohort of Connecticut
      physicians. DESIGN: A population-based mailing assessed the number of physicians
      practising in Connecticut. MEASUREMENTS: Information about practice site,
      practises pertaining to storing of patient information, sources of revenue and
      preferred method for receiving survey. Practice status in Connecticut, measured
      by yes and no. Demographic information was collected on gender, year of birth,
      race and ethnicity. RESULTS: The response rate for the postcard mailing was 19%
      (3105/16 462). Of the 16 462 unduplicated consumers, 233 (1%) were retired and
      5828 (35%) did not practise in Connecticut. Of the 3105 valid postcard responses
      we received, 2159 were for physicians practising in Connecticut. Nine (0.4%) of
      these responses did not specify a preferred method for receiving the full
      physician survey; 91 physicians refused to participate in the survey; 2159
      surveys were sent out using each physician's requested method for receiving the
      survey, that is, web-based, regular mail or telephone. As of August 2012, 898
      physicians had returned surveys, resulting in a response rate of 42%.
      LIMITATIONS: The postcard response rate based on the unduplicated lists adjusted
      for exclusions, such as death, retired and do not practise in Connecticut, is
      30%, which is low. We may be missing physicians' population which could greatly
      affect the indicators being used to measure change in electronic health record
      adoption rates. CONCLUSIONS: It is difficult to obtain an accurate physician
      count of practising physicians in Connecticut from the existing lists. States
      that are participating in the projects funded under various Office of the
      National Coordinator for Health Information Technology (ONC) initiatives must
      focus on getting an accurate count of the physicians practising in their state,
      since their progress is being measured based on this key number.

PMID- 23148339
TI  - A randomised efficacy and discontinuation study of etanercept versus adalimumab
      (RED SEA) for rheumatoid arthritis: a pragmatic, unblinded, non-inferiority study
      of first TNF inhibitor use: outcomes over 2 years.
AB  - OBJECTIVE: To compare adalimumab versus etanercept in patients with active
      rheumatoid arthritis (RA) to test the hypothesis that adalimumab was not inferior
      to etanercept in terms of drug continuation by a margin of 15% after 52 weeks of
      treatment. DESIGN: Pragmatic, randomised, parallel group, multicentre, unblinded
      and non-inferiority trial. Randomisation stratified by baseline use of
      methotrexate. PARTICIPANTS: 125 adults with active RA despite treatment with two
      disease-modifying drugs (DMARDs), including methotrexate randomised (1 : 1) to
      adalimumab 40 mg alternate weeks or etanercept 50 mg weekly, added to existing
      medication. MEASUREMENTS: The primary outcome was proportion of patients
      continuing treatment after 52 weeks. Secondary outcomes included: disease
      activity score using 28 joints (DAS28), treatment satisfaction (TSQM V.2), health
      status (Euroqol-5D), drug toxicity and persistence with therapy after 2 years.
      RESULTS: Persistence with therapy was 65% for adalimumab versus 56.7% for
      etanercept (one-sided 95% CI for proportion still taking adalimumab minus
      proportion on etanercept >=-7.9%); demonstrating non-inferiority at the 15%
      margin. After 2 years these figures were: adalimumab 58.3% and etanecept 43.3%
      (CI >=-1.7%). The proportion of good, moderate and non-responders based on DAS28
      C reactive protein, after 52 weeks, were 26.3%, 33.3% and 40.4%, respectively,
      for adalimumab versus 16.7%, 31.7% and 51.7%, respectively, for etanercept
      (p=0.158). Baseline median EQ-5D scores improved from 0.52 to 0.69 for adalimumab
      and from 0.52 to 0.64 for etanercept (p=0.046) after 52 weeks. Global
      satisfaction, effectiveness, side effects and convenience scores based on the
      TSQM were similar for both drugs. Fourteen serious adverse events occurred
      including two deaths from myocardial infarction, one patient with ovarian cancer
      and one with acute myeloid leukaemia. CONCLUSIONS: Clinicians choosing a first
      tumour necrosis factor inhibitor for active RA, despite trying two DMARDs
      including methotrexate, may choose either adalimumab or etanercept in the
      knowledge that these drugs are similarly effective. CLINICAL TRIAL REGISTRATION
      NUMBER: EU Clinical Trials Register 2006-006275-21/GB.

PMID- 23148341
TI  - Could screening participation bias symptom interpretation? An interview study on
      women's interpretations of and responses to cancer symptoms between mammography
      screening rounds.
AB  - OBJECTIVES: To explore how women with negative mammography screening results, but
      who were later diagnosed with interval breast cancer, reacted when they observed
      breast symptoms that could indicate malignancy in-between screening rounds.
      DESIGN: Semistructured individual interviews with women who have been diagnosed
      with breast cancer during mammography screening intervals. SETTING: Two breast
      diagnostic units covering two counties in Norway. PARTICIPANTS: 26 women
      diagnosed with interval breast cancer. RESULTS: Women with a screening negative
      result react in two ways when experiencing a possible symptom of breast cancer.
      Among 24 women with a self-detected palpable lesion, 14 sought medical advice
      immediately. Their argument was to dispose of potential cancer as soon as
      possible. Ten women delayed seeking medical advice, explaining their delay as a
      result of practical difficulties such as holidays, uncertainty about the symptom,
      and previous experiences of healthcare services' ability to handle diffuse
      symptoms. Also, a recent negative mammography scan led some women to assume that
      the palpable lesion was benign and wait for the next screening round.
      CONCLUSIONS: Participating in mammography screening may contribute to a postponed
      reaction to breast cancer symptoms, although most women acted rapidly when
      detecting a palpable breast lesion. Furthermore, screening participation does not
      necessarily increase awareness of breast cancer symptoms.

PMID- 23148340
TI  - Who is more likely to use doctor-rating websites, and why? A cross-sectional
      study in London.
AB  - OBJECTIVES: To explore the extent to which doctor-rating websites are known and
      used among a sample of respondents from London. To understand the main predictors
      of what makes people willing to use doctor-rating websites. DESIGN: A cross
      sectional study. SETTING: The Borough of Hammersmith and Fulham, London, England.
      PARTICIPANTS: 200 individuals from the borough. MAIN OUTCOME MEASURES: The
      likelihood of being aware of doctor-rating websites and the intention to use
      doctor-rating websites. RESULTS: The use and awareness of doctor-rating websites
      are still quite limited. White British subjects, as well as respondents with
      higher income are less likely to use doctor-rating websites. Aspects of the
      doctor-patient relationship also play a key role in explaining intention to use
      the websites. The doctor has both a 'complementary' and 'substitute' role with
      respect to Internet information. CONCLUSIONS: Online rating websites can play a
      major role in supporting patients' informed decisions on which healthcare
      providers to seek advice from, thus potentially fostering patients' choice in
      healthcare. Subjects who seek and provide feedback on doctor-ranking websites,
      though, are unlikely to be representative of the overall patients' pool. In
      particular, they tend to over-represent opinions from non-White British, medium
      low-income patients who are not satisfied with their choice of the healthcare
      treatments and the level of information provided by their GP. Accounting for
      differences in the users' characteristics is important when interpreting results
      from doctor-rating sites.

PMID- 23148342
TI  - Diagnostic value of patterns of symptoms and signs of heart failure: application
      of latent class analysis with concomitant variables in a cross-sectional study.
AB  - OBJECTIVE: The diagnosis of heart failure (HF) requires a compatible clinical
      syndrome and demonstration of cardiac dysfunction by imaging or functional tests.
      Since individual symptoms and signs are generally unreliable and have limited
      value for diagnosing HF, the authors aimed to identify patterns of symptoms and
      signs, based on findings routinely collected in current clinical practice, and to
      evaluate their diagnostic value, taking into account the a priori likelihood of
      HF. DESIGN: Cross-sectional evaluation. PARTICIPANTS: 1115 community participants
      aged >=45 years from Porto, Portugal, in 2006-2008. MAIN OUTCOMES MEASURES:
      Patterns were identified by latent class analysis, using concomitant variables to
      predict class membership. Patterns used 11 symptoms/signs, covering dimensions of
      congestion and hypoperfusion. Sex, age, education, obesity, diabetes and history
      of myocardial infarction or HF were included as concomitants. RESULTS: Bayesian
      information criteria supported a solution with three patterns: 10.1% of
      participants followed a pattern with symptoms of troubled breathing and signs of
      congestion (pattern 1), 27.8% a pattern characterised mainly by signs of
      congestion (pattern 2) and 62.1% were essentially asymptomatic (pattern 3); model
      fit was best when including concomitant variables. The likelihood ratio of
      patterns 1, 2 and 3 for left ventricular systolic dysfunction was 3.4, 1.1 and
      0.6, and for left ventricular diastolic dysfunction 3.5, 1.4 and 0.5,
      respectively. CONCLUSIONS: The use of concomitant variables can improve the
      diagnostic value of the symptoms and signs patterns and, consequently, improve
      the usefulness of the symptoms and signs for diagnosis and as an outcome measure.
      The potential for application in other settings of complex diagnoses is very
      high. These models were shown to be useful to standardise and quantify the
      probabilistic reasoning in clinical diagnosis, upon which decisions of further
      investigation and even treatment need to be made.

PMID- 23148343
TI  - General practitioner experience and perception of Child and Adolescent Mental
      Health Services (CAMHS) care pathways: a multimethod research study.
AB  - OBJECTIVES: This is a pilot study with the objective of investigating general
      practitioner (GP) perceptions and experiences in the referral of mentally ill and
      behaviourally disturbed children and adolescents. DESIGN: Quantitative analyses
      on patient databases were used to ascertain the source of referrals into Child
      and Adolescent Mental Health Services (CAMHS) and identify the relative
      contribution from GP practices. Qualitative semistructured interviews were then
      used to explore challenges faced by GPs in referring to CAMHS. SETTING: GPs were
      chosen from the five localities that deliver CAMHS within the local Trust
      (Peterborough City, Fenland, Huntingdon, Cambridge City and South
      Cambridgeshire). PARTICIPANTS: For the quantitative portion, data involving 19
      466 separate referrals were used. Seven GPs took part in the qualitative
      interviews. RESULTS: The likelihood of a referral from GPs being rejected by
      CAMHS was over three times higher compared to all other referral sources combined
      within the Cambridge and Peterborough NHS Foundation Trust. Interviews showed
      that detecting the signs and symptoms of mental illness in young people is a
      challenge for GPs. Communication with referral agencies varies and depends on
      individual relationships. GPs determine whether to refer on a mixture of the
      presenting conditions and their perceived likelihood of acceptance by CAMHS; the
      criteria for the latter were poorly understood by the interviewed GPs.
      CONCLUSIONS: There are longstanding structural weaknesses in the services for
      children and young people in general, reflected in poor multiagency cooperation
      at the primary care level. GP-friendly guidelines and standards are required that
      will aid in decision-making and help with understanding the referrals process. We
      look to managers of both commissioning and providing organisations, as well as
      future research, to drive forward the development of tools, protocols, and health
      service structures to help aid the recognition and treatment of mental illness in
      young people.

PMID- 23148344
TI  - An exploratory study on the consequences and contextual factors of intimate
      partner violence among immigrant and Canadian-born women.
AB  - OBJECTIVE: To compare immigrant and Canadian-born women on the physical and
      psychological consequences of intimate partner violence (IPV), as well as examine
      important sociodemographic, health and social support and network factors that
      may shape their experiences of abuse. METHOD: National, population-based, cross
      sectional survey conducted in 2009. PARTICIPANTS: 6859 women reported contact
      with a current or former partner in the previous 5 years, of whom 1480 reported
      having experienced emotional, financial, physical and/or sexual IPV. Of these
      women, 218 (15%) were immigrants and 1262 (85%) were Canadian-born. RESULTS:
      Immigrant women were less likely than Canadian-born women to report having
      experienced emotional abuse (15.3% vs 18.2%, p=0.04) and physical and/or sexual
      violence (5.1% vs 6.9%, p=0.04) from a current or former partner. There were no
      differences between immigrant and Canadian-born women in the physical and
      psychological consequences of physical and/or sexual IPV. However, compared with
      Canadian-born women, immigrant women reported lower levels of trust towards their
      neighbours (50.7% vs 41.5%, p=0.04) and people they work or go to school with
      (38.6% vs 27.5%, p=0.02), and were more likely to report having experienced
      discrimination based on ethnicity or culture (18.8% vs 6.8%, p<0.0001), race or
      skin colour (p=0.003) and language (10.1% vs 3.2%, p<0.0001). Immigrant women
      were less likely than Canadian-born women to report activity limitations (p=0.01)
      and medication use for sleep problems (14.1% vs 20.6%, p=0.05) and depression
      (11.5% vs 17.6%, p=0.05). CONCLUSIONS: Our exploratory study revealed no
      differences between immigrant and Canadian-born women in the physical and
      psychological consequences of IPV. Abused immigrant women's lower levels of trust
      for certain individuals and experiences of discrimination may have important
      implications for seeking help for IPV and underscores the need for IPV-related
      intervention and prevention services that are culturally sensitive and
      appropriate.

PMID- 23148345
TI  - Effect of bile acid sequestrants on glycaemic control: protocol for a systematic
      review with meta-analysis of randomised controlled trials.
AB  - INTRODUCTION: In addition to the lipid-lowering effect of bile acid sequestrants
      (BASs), they also lower blood glucose and, therefore, could be beneficial in the
      treatment of patients with type 2 diabetes mellitus (T2DM). Three oral BASs are
      approved by the US Food and Drug Administration (FDA) for the treatment of
      hypercholesterolaemia: colestipol, cholestyramine and colesevelam. The BAS
      colestimide/colestilan is used in Japan. Colesevelam was recently approved by the
      FDA for the treatment of T2DM. We plan to provide a systematic review with meta
      analysis of the glucose-lowering effect of BASs with the aim to evaluate their
      potential as glucose-lowering agents in patients with T2DM. METHODS AND ANALYSIS:
      In accordance with the preferred reporting items for systematic reviews and meta
      analyses statement, a systematic review with meta-analysis of randomised clinical
      trials of BASs (vs placebo, oral antidiabetes drugs or insulin), reporting
      measures of glycaemic control in adult patients with T2DM, will be performed.
      Change in glycated haemoglobin constitutes the primary endpoint, and secondary
      endpoints include changes in fasting plasma glucose, low-density lipoprotein
      cholesterol, high-density lipoprotein cholesterol, total cholesterol,
      triglycerides, body weight and body mass index and adverse events. Electronic
      searches will be performed in The Cochrane Library, MEDLINE and EMBASE, along
      with manual searches in the reference lists of relevant papers. The analyses will
      be performed based on individual patient data and summarised data. The primary
      meta-analysis will be performed using random effects models owing to expected
      intertrial heterogeneity. Dichotomous data will be analysed using risk difference
      and continuous data using weighted mean differences, both with 95% CIs. ETHICS
      AND DISSEMINATION: The study will evaluate the potential of BASs as glucose
      lowering agents and possibly contribute to the clinical management of patients
      with T2DM. RESULTS: The study will be disseminated by peer-review publication and
      conference presentation. PROTOCOL REGISTRATION: PROSPERO CRD42012002552.

PMID- 23148346
TI  - Geographical concentration of falciparum malaria treated in the UK and delay to
      treatment with artesunate in severe cases: an observational study.
AB  - OBJECTIVES: To quantify geographical concentration of falciparum malaria cases in
      the UK at a hospital level. To assess potential delay-to-treatment associated
      with hub-and-spoke distribution of artesunate in severe cases. DESIGN:
      Observational study using national and hospital data. SETTING AND PARTICIPANTS:
      3520 patients notified to the Malaria Reference Laboratory 2008-2010, 34 patients
      treated with intravenous artesunate from a tropical diseases centre 2002-2010.
      MAIN OUTCOME MEASURES: Geographical location of falciparum cases notified in the
      UK. Diagnosis-to-treatment times for intravenous artesunate. RESULTS: Eight
      centres accounted for 43.9% of the UK's total cases; notifications from 107
      centres accounted for 10.2% of cases; 51.5% of hospitals seeing malaria notified
      5 or fewer cases in 3 years. Centres that saw <10 cases/year treat 26.3% of
      malaria cases; 6.1% of cases are treated in hospitals seeing <2 cases/year.
      Concentration of falciparum malaria was highest in Greater London (1925, 54.7%),
      South East (515, 14.6%), East of England (402, 11.4%) and North West (192, 5.4%).
      The North East and Northern Ireland each notified 5 or fewer cases per year.
      Median diagnosis-to-treatment time was 1 h (range 0.5-5) for patients receiving
      artesunate in the specialist centre; 7.5 h (range 4-26) for patients receiving it
      in referring hospitals via the hub-and-spoke system (p=0.02); 25 h (range 9-45)
      for patients receiving it on transfer to the regional centre from a referring
      hospital (p=0.002). CONCLUSIONS: Most UK hospitals see few cases of falciparum
      malaria and geographical distances are significant. Over 25% of cases are seen in
      hospitals where malaria is rare, although 60% are seen in hospitals seeing over
      50 cases over 3 years. A hub-and-spoke system minimises drug wastage and ensures
      availability in centres seeing most cases but is associated with treatment delays
      elsewhere. As with all observational studies, there are limitations, which are
      discussed.

PMID- 23148347
TI  - Is thiazolidinediones use a factor in delaying the need for insulin therapy in
      type 2 patients with diabetes? A population-based cohort study.
AB  - OBJECTIVE: To understand the independent role of thiazolidinediones (TZDs) in
      delaying progression to parenteral insulin therapy. DESIGN: Population-based
      retrospective cohort study. SETTING: British Columbia, Canada. PARTICIPANTS: A
      total of 18 867 type 2 diabetes patients (mean age 58.9) treated with metformin
      as first-line therapy who then switched or added a TZD or sulphonylurea as a
      second-line treatment between 1 January 1998 and 31 March 2008. OUTCOME MEASURES:
      Multivariable Poisson regression models were used to estimate the effect of using
      TZD compared to sulphonylureas on time to the initiation of insulin treatment
      (third-line). RESULTS: The adjusted rate difference in women aged <60 showed 2.22
      fewer insulin initiation events per 100 person-years (PYs) in the TZD group
      versus the sulphonylurea group (95% CI -3.46 to -0.99). Men in the same age group
      had 1.50 fewer insulin initiation events per 100 PYs in the TZD group versus the
      sulphonylurea group (95% CI -2.44 to -0.56). The average time in days to
      initiation on insulin in the sulphonylurea, rosiglitazone and pioglitazone group
      was 343, 252 and 339, respectively. The cumulative hazard for starting insulin
      for sulphonylurea patients at 12, 24, 36 and 48 months was approximately three
      times higher compared to TZD patients. CONCLUSIONS: Second-line TZD therapy
      compared to second-line sulphonylurea therapy was associated with a lower
      incidence of insulin initiation as third-line treatment in patients with type 2
      diabetes, with a mean delay of 90 days. This duration of delay must be weighed
      against the absence of a proven reduction in morbidity or mortality with TZDs and
      their known serious cardiovascular harm.

PMID- 23148348
TI  - Support and assessment for fall emergency referrals (SAFER 2) research protocol:
      cluster randomised trial of the clinical and cost effectiveness of new protocols
      for emergency ambulance paramedics to assess and refer to appropriate community
      based care.
AB  - INTRODUCTION: Emergency calls to ambulance services are frequent for older people
      who have fallen, but ambulance crews often leave patients at the scene without
      ongoing care. Evidence shows that when left at home with no further support older
      people often experience subsequent falls which result in injury and emergency
      department attendances. SAFER 2 is an evaluation of a new clinical protocol which
      allows paramedics to assess and refer older people who have fallen, and do not
      need hospital care, to community-based falls services. In this protocol paper, we
      report methods and progress during trial implementation. SAFER 2 is recruiting
      patients through three ambulance services. A successful trial will provide robust
      evidence about the value of this new model of care, and enable ambulance services
      to use resources efficiently. DESIGN: Pragmatic cluster randomised trial. METHODS
      AND ANALYSIS: We randomly allocated 25 participating ambulance stations
      (clusters) in three services to intervention or control group. Intervention
      paramedics received training and clinical protocols for assessing and referring
      older people who have fallen to community-based falls services when appropriate,
      while control paramedics deliver care as usual. Patients are eligible for the
      trial if they are aged 65 or over; resident in a participating falls service
      catchment area; and attended by a trial paramedic following an emergency call
      coded as a fall without priority symptoms. The principal outcome is the rate of
      further emergency contacts (or death), for any cause and for falls. Secondary
      outcomes include further falls, health-related quality of life, 'fear of
      falling', patient satisfaction reported by participants through postal
      questionnaires at 1 and 6 months, and quality and pathways of care at the index
      incident. We shall compare National Health Service (NHS) and patient/carer costs
      between intervention and control groups and estimate quality-adjusted life years
      (QALYs) gained from the intervention and thus incremental cost per QALY. We shall
      estimate wider system effects on key-performance indicators. We shall interview
      60 intervention patients, and conduct focus groups with contributing NHS staff to
      explore their experiences of the assessment and referral service. We shall
      analyse quantitative trial data by 'treatment allocated'; and qualitative data
      using content analysis. ETHICS AND DISSEMINATION: The Research Ethics Committee
      for Wales gave ethical approval and each participating centre gave NHS Research
      and Development approval. We shall disseminate study findings through peer
      reviewed publications and conference presentations. TRIAL REGISTRATION: ISRCTN
      60481756.

PMID- 23148350
TI  - Progression of auditory discrimination based on neural decoding predicts
      awakening from coma.
AB  - Auditory evoked potentials are informative of intact cortical functions of
      comatose patients. The integrity of auditory functions evaluated using mismatch
      negativity paradigms has been associated with their chances of survival. However,
      because auditory discrimination is assessed at various delays after coma onset,
      it is still unclear whether this impairment depends on the time of the recording.
      We hypothesized that impairment in auditory discrimination capabilities is
      indicative of coma progression, rather than of the comatose state itself and that
      rudimentary auditory discrimination remains intact during acute stages of coma.
      We studied 30 post-anoxic comatose patients resuscitated from cardiac arrest and
      five healthy, age-matched controls. Using a mismatch negativity paradigm, we
      performed two electroencephalography recordings with a standard 19-channel
      clinical montage: the first within 24 h after coma onset and under mild
      therapeutic hypothermia, and the second after 1 day and under normothermic
      conditions. We analysed electroencephalography responses based on a multivariate
      decoding algorithm that automatically quantifies neural discrimination at the
      single patient level. Results showed high average decoding accuracy in
      discriminating sounds both for control subjects and comatose patients.
      Importantly, accurate decoding was largely independent of patients' chance of
      survival. However, the progression of auditory discrimination between the first
      and second recordings was informative of a patient's chance of survival. A
      deterioration of auditory discrimination was observed in all non-survivors
      (equivalent to 100% positive predictive value for survivors). We show, for the
      first time, evidence of intact auditory processing even in comatose patients who
      do not survive and that progression of sound discrimination over time is
      informative of a patient's chance of survival. Tracking auditory discrimination
      in comatose patients could provide new insight to the chance of awakening in a
      quantitative and automatic fashion during early stages of coma.

PMID- 23148359
TI  - Q&A: George Sledge on trends in clinical trials. Interview by Eric Bender.

PMID- 23148349
TI  - Psychophysiological prediction of choice: relevance to insight and drug
      addiction.
AB  - An important goal of addiction research and treatment is to predict behavioural
      responses to drug-related stimuli. This goal is especially important for patients
      with impaired insight, which can interfere with therapeutic interventions and
      potentially invalidate self-report questionnaires. This research tested (i)
      whether event-related potentials, specifically the late positive potential,
      predict choice to view cocaine images in cocaine addiction; and (ii) whether such
      behaviour prediction differs by insight (operationalized in this study as self
      awareness of image choice). Fifty-nine cocaine abusers and 32 healthy controls
      provided data for the following laboratory components that were completed in a
      fixed-sequence (to establish prediction): (i) event-related potential recordings
      while passively viewing pleasant, unpleasant, neutral and cocaine images, during
      which early (400-1000 ms) and late (1000-2000 ms) window late positive potentials
      were collected; (ii) self-reported arousal ratings for each picture; and (iii)
      two previously validated tasks: one to assess choice for viewing these same
      images, and the other to group cocaine abusers by insight. Results showed that
      pleasant-related late positive potentials and arousal ratings predicted pleasant
      choice (the choice to view pleasant pictures) in all subjects, validating the
      method. In the cocaine abusers, the predictive ability of the late positive
      potentials and arousal ratings depended on insight. Cocaine-related late positive
      potentials better predicted cocaine image choice in cocaine abusers with impaired
      insight. Another emotion-relevant event-related potential component (the early
      posterior negativity) did not show these results, indicating specificity of the
      late positive potential. In contrast, arousal ratings better predicted respective
      cocaine image choice (and actual cocaine use severity) in cocaine abusers with
      intact insight. Taken together, the late positive potential could serve as a
      biomarker to help predict drug-related choice--and possibly associated behaviours
      (e.g. drug seeking in natural settings, relapse after treatment)--when insight
      (and self-report) is compromised.

PMID- 23148360
TI  - Emphasizing the provocative.

PMID- 23148371
TI  - Fingerprinting acute leukemia: DNA methylation profiling of B-acute lymphoblastic
      leukemia.
AB  - In this issue of Cancer Discovery, Geng and colleagues report on their use of a
      combination of promoter cytosine methylation profiling with gene expression and
      ChIP sequencing to elucidate molecular signatures of adult B-acute lymphoblastic
      leukemia patient samples with BCR-ABL1, E2A-PBX1, and MLL rearrangements. The
      unique epigenetic and gene expression signatures of these clinically unfavorable
      B-ALL subtypes identify novel biomarkers and provide a strong rationale for
      repurposing existing therapies to treat these molecularly distinct diseases.

PMID- 23148372
TI  - Distinct epigenetic mechanisms distinguish TMPRSS2-ERG fusion-positive and 
      negative prostate cancers.
AB  - This issue of Cancer Discovery features an article that describes distinct
      epigenetic mechanisms that operate in TMPRSS2-ERG fusion-negative prostate
      cancers. This finding clarifies molecular features of these TMPRSS2-ERG fusion
      negative tumors and may have implications for how to treat this prostate cancer
      subtype.

PMID- 23148373
TI  - The promise of combining inhibition of PI3K and PARP as cancer therapy.
AB  - Analyses of in vitro and patient-derived in vivo models of breast cancer reveal
      that a combination of inhibitors of the enzymes PARP and phosphoinositide 3
      kinase (PI3K) is a potentially effective treatment regimen for breast cancer
      tumors with elevated activity of the PI3K pathway.

PMID- 23148392
TI  - Superior mesenteric artery dissection.

PMID- 23148393
TI  - Ectopic tubal choriocarcinoma: a rarity.
AB  - Herein, we present a case of tubal choriocarcinoma which was diagnosed initially
      as chronic ectopic pregnancy. During laparotomy we noticed a haemorrhagic friable
      mass in the left flank, adherent to the bowel. Left-sided salpingoopherectomy was
      performed. Serum beta HCG (human chorionic gonadotropin) levels performed in the
      postoperative period were elevated. Histopathology demonstrated choriocarcinoma.
      She was given six cycles of chemotherapy (etoposide, methotrexate, actinomycin D
      cyclophosphamide, vincristine/oncovine (EMA-CO) regime) and monitored by serial
      beta HCG estimation. This case highlights the importance of undertaking
      histopathological examination of the tubal tissue in every patient who presents
      with ectopic pregnancy. This important diagnostic test prevents the potential of
      missing this rare and highly malignant disease which is otherwise curable in most
      instances.

PMID- 23148394
TI  - Perthes' disease and femoroacetabular impingement in a child with proximal
      femoral focal deficiency.
AB  - A girl with known proximal femoral focal deficiency presented with Perthes'
      disease at 5 years of age. Her treatment involved a Salter osteotomy. This in
      conjunction with articular incongruence, due to deformity of the femoral head,
      resulted in mixed type femoroacetabular impingement when she was 10 years old.
      Surgical hip dislocation and femoral neck osteochondroplasty successfully
      relieved her symptoms of impingement. This is the first reported case of Perthes'
      disease in a patient with proximal femoral focal deficiency. The case highlights
      the importance of thoroughly investigating pain in patients with proximal femoral
      focal deficiency, a condition which is normally painless. Timely diagnosis of
      Perthes' disease and containment procedures can prevent collapse of the femoral
      head and the resultant sequelae. Acetabular over-coverage should be avoided in
      pelvic osteotomy to prevent the development of femoroacetabular impingement.

PMID- 23148395
TI  - Treatment of hypertrophic osteoarthropathy in the case of pulmonary metastasis
      secondary-to-nasopharyngeal carcinoma with zoledronic acid: an enlightening
      experience.
AB  - We describe a case of 23-year-old man, who presented with painful hypertrophic
      pulmonary osteoarthropathy involving bilateral upper and lower extremities,
      resulting from intrathoracic metastasis. The patient had a history of
      undifferentiated nasopharyngeal carcinoma which was treated successfully 2 years
      ago. The painful osteoarthropathy had made the patient incapacitated. A single
      dose of 4 mg of intravenous zoledronic acid (ZA) was given which resulted in
      complete resolution of pain along with reduction of swelling. There was no
      recurrence on follow-up. Bisphosphonates by their action on bone metabolism might
      alleviate the symptoms and its use should be encouraged in cancer patients with
      debilitating arthropathies. This article aims at highlighting the role of
      bisphosphonates, particularly ZA in managing patients with hypertrophic
      osteoarthropathy (HOA) and sharing our experience with this drug because of the
      rarity of the condition and lack of sufficient data in the medical literature.

PMID- 23148397
TI  - A 'One in a million' case of pulsating thoracoabdominal mass.
AB  - Ectopia cordis is a rare congenital malformation in which the heart is located
      partially or totally outside the thoracic cavity. It comprises 0.1% of congenital
      heart diseases. The authors present a case of a male baby born at term by
      emergency caesarean section due to prolonged fetal bradycardia, who was noted to
      have a large pulsating mass in the thoracoabdominal area. In view of lower
      thoracolumbar abdominal defect, ectopic placement of the umbilicus, deficiency of
      the diaphragmatic pericardium, deficiency of anterior diaphragm and intracardiac
      abnormalities, a diagnosis of ectopia cordis-Pentalogy of Cantrell was made. He
      was transferred to a tertiary centre and required oxygen supplement initially. He
      was sent home after 1 week, on propanolol, with weekly oxygen saturation checks.
      He is awaiting further surgical intervention pending the required weight gain.

PMID- 23148396
TI  - Delayed presentation of scorpion sting with cardiogenic shock.
AB  - A young farmer presented with cardiogenic shock 5 days after a scorpion sting. He
      was managed with norepinephrine, atropine and supportive measures and made a
      complete recovery. The role of atropine in treating scorpion sting has to be
      defined better.

PMID- 23148398
TI  - Intracranial venous sinus thrombosis mimicking Lhermitte Duclos disease.
AB  - A middle-aged man presented with 1-month history of headache, dizziness,
      staggering of gait and progressive deafness. Examination revealed decreased
      visual acuity, papilloedema, gaze evoked nystagmus, bilateral sensorineural
      deafness and gait ataxia. MRI showed TI iso and T2 hyperintensity of cerebellum,
      prominence of folia with gyral enhancement in a tigroid pattern making impression
      of the rare entity, Lhermitte Duclos disease (LDD) or dysplastic gangliocytoma of
      cerebellum. Conservative management for the raised intra cranial pressure did not
      have any impact on patient's general condition for which an MR venogram was
      planned and it surprisingly showed non-visualisation of left transverse sinus and
      internal jugular vein, suggestive of thrombosis. Patient was treated with
      anticoagulants but he succumbed to his illness soon after. We present this case
      to convey that a high index of suspicion should always be there in mind for this
      commoner condition (venous sinus thrombosis) before diagnosing the rarer ones
      (here LDD disease) to prevent the disastrous consequences of the former.

PMID- 23148399
TI  - A sticky situation: methaemaglobinaemia in a hand trauma patient.
AB  - We describe a case of methaemoglobinaemia (MtHb) in a previously healthy 39-year
      old gentleman who presented with a traumatic glass laceration to his right wrist
      that required emergency surgery to control bleeding and repair his ulnar artery.
      The MtHb was noted on blood gas analysis by the anaesthetist after the patient
      had a drop in arterial oxygen saturation under general anaesthetic. We initially
      suspected the lidocaine local anaesthetic injected proximal to his wound for pain
      control in the emergency department an hour preoperatively, but then discovered
      that the patient was a recreational user of 'poppers' and had in fact been using
      these drugs just before his injury and hospitalisation. The patient's condition
      stabilised overnight with conservative management. Given how commonly hand
      surgeons and other clinical staff use local anaesthetics, we reviewed the
      literature on this uncommon, but potentially fatal, complication, its causes and
      evidence-based management.

PMID- 23148400
TI  - Unusual presentation of spontaneous splenic haematoma due to severe pancreatitis:
      a cautionary tale.
AB  - We report the case of a patient with multiple splenic complications from chronic
      pancreatitis with pseudocyst formation, including splenic vein thrombosis,
      subcapsular splenic haematoma and splenic artery pseudoaneurysm. The initial
      presentation was associated with pleuritic chest pain, clinically resembling
      symptoms of pulmonary embolism. The patient was treated with therapeutic low
      molecular-weight heparin, without confirmatory imaging. However, the latter
      arranged computed tomographic pulmonary angiogram was negative, while the
      abdominal sequences of the CT revealed the splenic haematoma as causative
      pathology. The patient was initially treated conservatively, and discharged from
      inpatient care. On a subsequent CT, a pseudoaneurysm of the splenic artery was
      found and treated with coil embolisation. The patient is currently awaiting
      definitive management of the pancreatic pseudocyst.

PMID- 23148401
TI  - Blood-stream infection and atrial thrombus due to a buried and forgotten
      permanent haemodialysis catheter.

PMID- 23148402
TI  - Delayed presentation of post-traumatic diaphragm rupture repaired by laparoscopy.
AB  - Diaphragmatic rupture is a serious but frequently missed condition that is
      potentially curable. While surgical management has classically been performed
      through open thoracotomy, a laparoscopic approach has been suggested as a
      preferable alternative. A man in his mid-50s presented with non-specific
      abdominal symptoms, 8 months after falling down some stairs. Diaphragmatic
      rupture was suspected after old rib fractures were noticed on an admitting chest
      radiograph. Further signs and symptoms presented following deterioration due to
      the unstable pathology. Prompt surgical treatment using laparoscopy was attempted
      with success and resulted in rapid and lasting improvement in symptoms.

PMID- 23148404
TI  - Mapping the dawn of nanoecotoxicological research.
AB  - Some researchers consider nanotechnology the next industrial revolution, and
      consumer products and a variety of industries increasingly use synthetic
      nanoparticles. In this Account, we review the initial accomplishments of
      nanoecotoxicology, a discipline that is just a decade old. This new subdiscipline
      of ecotoxicology faces two important and challenging problems: the analysis of
      the safety of nanotechnologies in the natural environment and the promotion of
      sustainable development while mitigating the potential pitfalls of innovative
      nanotechnologies. In this Account, we provide a snapshot of the publicly
      available scientific information regarding the ecotoxicity of engineered
      nanoparticles. We pay special attention to information relevant to aquatic
      freshwater species commonly used for risk assessment and regulation. Just as the
      development of ecotoxicology has lagged behind that of toxicology,
      nanoecotoxicological research has developed much more slowly than nanotoxicology.
      Although the first nanotoxicolology papers were published in 1990s, the first
      nanoecotoxicology papers came out in 2006. A meta-analysis of scientific
      publications covering different environmental impacts of nanomaterials showed
      that the importance of research into the environmental impact of nanotechnology
      has gradually increased since 2005. Now the most frequently cited papers in the
      environmental disciplines are often those that focus on synthetic nanoparticles.
      The first nanoecotoxicology studies focused on adverse effects of nanoparticles
      on fish, algae and daphnids, which are ecotoxicological model organisms for
      classification and labeling of chemicals (these model organisms are also used in
      the EU chemical safety policy adopted in 2007: Registration, Evaluation,
      Authorization, and Restriction of Chemicals (REACH)). Based on our experience, we
      propose a multitrophic battery of nanoecotoxicological testing that includes
      particle-feeding and a priori particle-"proof" prokaryotic and eukaryotic
      organisms at different food-chain levels. Using this battery of selected test
      organisms, we demonstrated that TiO2 nanoparticles were toxic to algae and that
      ZnO and CuO nanoparticles were toxic to several aquatic invertebrate test
      species. Thus, one single biotest cannot predict the ecotoxicological effects of
      chemicals/nanoparticles, and researchers should use several tests instead.
      Moreover, produced nanoparticles usually vary in features such as size, shape,
      and coating; therefore, a single nanoparticle species may actually include many
      entities with different physicochemical properties. An ecotoxicity analysis of
      all these variants would require a huge number of laboratory tests. To address
      these issues, high throughput bioassays and computational (QSAR) models that
      serve as powerful alternatives to conventional (eco)toxicity testing must be
      implemented to handle both the diversity of nanomaterials and the complexity of
      ecosystems.

PMID- 23148403
TI  - Cirrhosis, cellulitis and cats: a 'purrfect' combination for life-threatening
      spontaneous bacterial peritonitis from Pasteurella multocida.
AB  - Pasteurella multocida is a Gram-negative coccobacillus that colonises the upper
      airways of many animals, in particular, dogs and cats. It acts as an
      opportunistic infection in humans following an animal bite or scratch and is
      associated with soft tissue infections, septicaemia and pneumonia, particularly
      in patients with a compromised immune response, such as patients with liver
      failure. Spontaneous bacterial peritonitis (SBP) is a serious complication of
      cirrhosis with a death rate of 10-15%. We report a case of a 47-year-old man with
      cirrhosis who presented with life-threatening P multocida SBP and bacteraemia
      secondary to a lick from a cat to a cellulitic leg wound. This case highlights
      the potential severity of an infection from domestic animals and an otherwise
      innocuous organism in an immunocompromised host.

PMID- 23148407
TI  - The kernel semi-least squares method for sparse distance approximation.
AB  - We extend the semi-least squares problem defined by Rao and Mitra ( 1971 ) to the
      kernel semi-least squares problem. We introduce subset projection, a technique
      that produces a solution to this problem. We show how the results of subset
      projection can be used to approximate a computationally expensive distance
      metric.

PMID- 23148408
TI  - Temporal order detection and coding in nervous systems.
AB  - This letter discusses temporal order coding and detection in nervous systems.
      Detection of temporal order in the external world is an adaptive function of
      nervous systems. In addition, coding based on the temporal order of signals can
      be used as an internal code. Such temporal order coding is a subset of temporal
      coding. We discuss two examples of processing the temporal order of external
      events: the auditory location detection system in birds and the visual direction
      detection system in flies. We then discuss how somatosensory stimulus intensities
      are translated into a temporal order code in the human peripheral nervous system.
      We next turn our attention to input order coding in the mammalian cortex. We
      review work demonstrating the capabilities of cortical neurons for detecting
      input order. We then discuss research refuting and demonstrating the
      representation of stimulus features in the cortex by means of input order. After
      some general theoretical considerations on input order detection and coding, we
      conclude by discussing the existing and potential use of input order coding in
      neuromorphic engineering.

PMID- 23148409
TI  - Impact of correlated neural activity on decision-making performance.
AB  - Stimulus from the environment that guides behavior and informs decisions is
      encoded in the firing rates of neural populations. Neurons in the populations,
      however, do not spike independently: spike events are correlated from cell to
      cell. To what degree does this apparent redundancy have an impact on the accuracy
      with which decisions can be made and the computations required to optimally
      decide? We explore these questions for two illustrative models of correlation
      among cells. Each model is statistically identical at the level of pairwise
      correlations but differs in higher-order statistics that describe the
      simultaneous activity of larger cell groups. We find that the presence of
      correlations can diminish the performance attained by an ideal decision maker to
      either a small or large extent, depending on the nature of the higher-order
      correlations. Moreover, although this optimal performance can in some cases be
      obtained using the standard integration-to-bound operation, in others it requires
      a nonlinear computation on incoming spikes. Overall, we conclude that a given
      level of pairwise correlations, even when restricted to identical neural
      populations, may not always indicate redundancies that diminish decision-making
      performance.

PMID- 23148410
TI  - Accelerated spike resampling for accurate multiple testing controls.
AB  - Controlling for multiple hypothesis tests using standard spike resampling
      techniques often requires prohibitive amounts of computation. Importance sampling
      techniques can be used to accelerate the computation. The general theory is
      presented, along with specific examples for testing differences across conditions
      using permutation tests and for testing pairwise synchrony and precise lagged
      correlation between many simultaneously recorded spike trains using interval
      jitter.

PMID- 23148411
TI  - Supervised learning in multilayer spiking neural networks.
AB  - We introduce a supervised learning algorithm for multilayer spiking neural
      networks. The algorithm overcomes a limitation of existing learning algorithms:
      it can be applied to neurons firing multiple spikes in artificial neural networks
      with hidden layers. It can also, in principle, be used with any linearizable
      neuron model and allows different coding schemes of spike train patterns. The
      algorithm is applied successfully to classic linearly nonseparable benchmarks
      such as the XOR problem and the Iris data set, as well as to more complex
      classification and mapping problems. The algorithm has been successfully tested
      in the presence of noise, requires smaller networks than reservoir computing, and
      results in faster convergence than existing algorithms for similar tasks such as
      SpikeProp.

PMID- 23148412
TI  - Enhanced gradient for training restricted Boltzmann machines.
AB  - Restricted Boltzmann machines (RBMs) are often used as building blocks in greedy
      learning of deep networks. However, training this simple model can be laborious.
      Traditional learning algorithms often converge only with the right choice of
      metaparameters that specify, for example, learning rate scheduling and the scale
      of the initial weights. They are also sensitive to specific data representation.
      An equivalent RBM can be obtained by flipping some bits and changing the weights
      and biases accordingly, but traditional learning rules are not invariant to such
      transformations. Without careful tuning of these training settings, traditional
      algorithms can easily get stuck or even diverge. In this letter, we present an
      enhanced gradient that is derived to be invariant to bit-flipping
      transformations. We experimentally show that the enhanced gradient yields more
      stable training of RBMs both when used with a fixed learning rate and an adaptive
      one.

PMID- 23148413
TI  - Stochastic optimal control as a theory of brain-machine interface operation.
AB  - The closed-loop operation of brain-machine interfaces (BMI) provides a framework
      to study the mechanisms behind neural control through a restricted output
      channel, with emerging clinical applications to stroke, degenerative disease, and
      trauma. Despite significant empirically driven improvements in closed-loop BMI
      systems, a fundamental, experimentally validated theory of closed-loop BMI
      operation is lacking. Here we propose a compact model based on stochastic optimal
      control to describe the brain in skillfully operating canonical decoding
      algorithms. The model produces goal-directed BMI movements with sensory feedback
      and intrinsically noisy neural output signals. Various experimentally validated
      phenomena emerge naturally from this model, including performance deterioration
      with bin width, compensation of biased decoders, and shifts in tuning curves
      between arm control and BMI control.   Analysis of the model provides insight
      into possible mechanisms underlying these behaviors, with testable predictions.
      Spike binning may erode performance in part from intrinsic control-dependent
      constraints, regardless of decoding accuracy. In compensating decoder bias, the
      brain may incur an energetic cost associated with action potential production.
      Tuning curve shifts, seen after the mastery of a BMI-based skill, may reflect the
      brain's implementation of a new closed-loop control policy. The direction and
      magnitude of tuning curve shifts may be altered by decoder structure, ensemble
      size, and the costs of closed-loop control. Looking forward, the model provides a
      framework for the design and simulated testing of an emerging class of BMI
      algorithms that seek to directly exploit the presence of a human in the loop.

PMID- 23148414
TI  - A spike-timing-based integrated model for pattern recognition.
AB  - During the past few decades, remarkable progress has been made in solving pattern
      recognition problems using networks of spiking neurons. However, the issue of
      pattern recognition involving computational process from sensory encoding to
      synaptic learning remains underexplored, as most existing models or algorithms
      target only part of the computational process. Furthermore, many learning
      algorithms proposed in the literature neglect or pay little attention to sensory
      information encoding, which makes them incompatible with neural-realistic sensory
      signals encoded from real-world stimuli. By treating sensory coding and learning
      as a systematic process, we attempt to build an integrated model based on spiking
      neural networks (SNNs), which performs sensory neural encoding and supervised
      learning with precisely timed sequences of spikes. With emerging evidence of
      precise spike-timing neural activities, the view that information is represented
      by explicit firing times of action potentials rather than mean firing rates has
      been receiving increasing attention. The external sensory stimulation is first
      converted into spatiotemporal patterns using a latency-phase encoding method and
      subsequently transmitted to the consecutive network for learning. Spiking neurons
      are trained to reproduce target signals encoded with precisely timed spikes. We
      show that when a supervised spike-timing-based learning is used, different
      spatiotemporal patterns are recognized by different spike patterns with a high
      time precision in milliseconds.

PMID- 23148415
TI  - Dynamical movement primitives: learning attractor models for motor behaviors.
AB  - Nonlinear dynamical systems have been used in many disciplines to model complex
      behaviors, including biological motor control, robotics, perception, economics,
      traffic prediction, and neuroscience. While often the unexpected emergent
      behavior of nonlinear systems is the focus of investigations, it is of equal
      importance to create goal-directed behavior (e.g., stable locomotion from a
      system of coupled oscillators under perceptual guidance). Modeling goal-directed
      behavior with nonlinear systems is, however, rather difficult due to the
      parameter sensitivity of these systems, their complex phase transitions in
      response to subtle parameter changes, and the difficulty of analyzing and
      predicting their long-term behavior; intuition and time-consuming parameter
      tuning play a major role. This letter presents and reviews dynamical movement
      primitives, a line of research for modeling attractor behaviors of autonomous
      nonlinear dynamical systems with the help of statistical learning techniques. The
      essence of our approach is to start with a simple dynamical system, such as a set
      of linear differential equations, and transform those into a weakly nonlinear
      system with prescribed attractor dynamics by means of a learnable autonomous
      forcing term. Both point attractors and limit cycle attractors of almost
      arbitrary complexity can be generated. We explain the design principle of our
      approach and evaluate its properties in several example applications in motor
      control and robotics.

PMID- 23148416
TI  - Three-dimensional graphene-based macro- and mesoporous frameworks for high
      performance electrochemical capacitive energy storage.
AB  - Three-dimensional graphene-based frameworks (3D-GFs) with hierarchical macro- and
      meso-porous structures are presented. The interconnected macropores are derived
      from hydrothermally assembled 3D graphene aerogels (GAs), while the mesopores are
      generated by the silica networks uniformly grown on the surface of graphene. The
      resulting 3D-GFs exhibit narrow mesopore size distribution (2-3.5 nm), high
      surface area, and low mass density. These intriguing features render 3D-GFs a
      promising template for creating various 3D porous materials. Specifically, 3D GA
      based mesoporous carbons (GA-MC) and metal oxide hybrids (GA-Co(3)O(4), GA
      RuO(2)) can be successfully constructed via a nanocasting technology. Benefiting
      from the integration of meso- and macroporous structures, 3D GA-MC manifests
      outstanding specific capacitance (226 F g(-1)), high rate capability, and
      excellent cycling stability (no capacitance loss after 5000 cycles) when it is
      applied in electrochemical capacitors.

PMID- 23148420
TI  - Wanted: a FRAME for staging functional decline in older adults.

PMID- 23148419
TI  - Conjugating phosphospermines to siRNAs for improved stability in serum,
      intracellular delivery and RNAi-mediated gene silencing.
AB  - siRNAs are usually formulated with cationic polymers or lipids to form
      supramolecular particles capable of binding and crossing the negatively charged
      cell membrane. However, particles hardly diffuse through tissues when
      administered in vivo. We therefore are developing cationic siRNAs, composed of an
      antisense sequence annealed to an oligophosphospermine-conjugated sense strand.
      Cationic siRNAs have been previously shown to display gene silencing activity in
      human cell line (Nothisen et al. J. Am. Chem. Soc.2009). We have improved the
      synthesis, purification and characterization of oligospermine-oligoribonucleotide
      conjugates which provide cationic siRNAs with enhanced biological activity. We
      show data supporting their carrier-free intracellular delivery in a molecular,
      soluble state. Additional results on the relationship between global charge,
      uptake and silencing activity confirm the requirement for an overall positive
      charge of the conjugated siRNA in order to enter cells. Importantly, conjugated
      siRNAs made of natural phosphodiester nucleotides are protected from nuclease
      degradation by the oligophosphospermine moiety, operate through the RNAi
      mechanism and mediate specific gene silencing at submicromolar concentration in
      the presence of serum. 

PMID- 23148417
TI  - Quantitative fluorescence loss in photobleaching for analysis of protein
      transport and aggregation.
AB  - BACKGROUND: Fluorescence loss in photobleaching (FLIP) is a widely used imaging
      technique, which provides information about protein dynamics in various cellular
      regions. In FLIP, a small cellular region is repeatedly illuminated by an intense
      laser pulse, while images are taken with reduced laser power with a time lag
      between the bleaches. Despite its popularity, tools are lacking for quantitative
      analysis of FLIP experiments. Typically, the user defines regions of interest
      (ROIs) for further analysis which is subjective and does not allow for comparing
      different cells and experimental settings. RESULTS: We present two complementary
      methods to detect and quantify protein transport and aggregation in living cells
      from FLIP image series. In the first approach, a stretched exponential (StrExp)
      function is fitted to fluorescence loss (FL) inside and outside the bleached
      region. We show by reaction-diffusion simulations, that the StrExp function can
      describe both, binding/barrier-limited and diffusion-limited FL kinetics. By
      pixel-wise regression of that function to FL kinetics of enhanced green
      fluorescent protein (eGFP), we determined in a user-unbiased manner from which
      cellular regions eGFP can be replenished in the bleached area. Spatial variation
      in the parameters calculated from the StrExp function allow for detecting
      diffusion barriers for eGFP in the nucleus and cytoplasm of living cells.
      Polyglutamine (polyQ) disease proteins like mutant huntingtin (mtHtt) can form
      large aggregates called inclusion bodies (IB's). The second method combines
      single particle tracking with multi-compartment modelling of FL kinetics in
      moving IB's to determine exchange rates of eGFP-tagged mtHtt protein (eGFP-mtHtt)
      between aggregates and the cytoplasm. This method is self-calibrating since it
      relates the FL inside and outside the bleached regions. It makes it therefore
      possible to compare release kinetics of eGFP-mtHtt between different cells and
      experiments. CONCLUSIONS: We present two complementary methods for quantitative
      analysis of FLIP experiments in living cells. They provide spatial maps of
      exchange dynamics and absolute binding parameters of fluorescent molecules to
      moving intracellular entities, respectively. Our methods should be of great value
      for quantitative studies of intracellular transport.

PMID- 23148421
TI  - Multiple findings in elderly adults with confirmed Alzheimer's disease.

PMID- 23148422
TI  - Measures to support voluntary retirement from driving in Japanese older people:
      driving is not just a means of transportation.

PMID- 23148423
TI  - Lay concept of aging well according to age: a reanalysis.

PMID- 23148424
TI  - Underrecognition of weight loss in community-dwelling elderly adults.

PMID- 23148425
TI  - Using a Chinese radio station to disseminate dementia knowledge to Chinese
      Americans.

PMID- 23148426
TI  - Identifying differences in communication technology preferences across the
      lifespan.

PMID- 23148427
TI  - The electronic health record and improving quality for hospitalized elderly
      adults.

PMID- 23148428
TI  - Assessment of patient dignity in geriatric palliative care.

PMID- 23148429
TI  - Using clinical practice guidelines in multimorbid older adults--a challenging
      clinical dilemma.

PMID- 23148430
TI  - Normal pressure hydrocephalus associated with delirium in an elderly man who had
      undergone aortic valve replacement surgery.

PMID- 23148431
TI  - Cognitive aging, geriatrics textbooks, and unintentional ageism.

PMID- 23148432
TI  - Last resort of individuals with dementia threatened.

PMID- 23148433
TI  - Comment on "Emphysematous infections of the prostate and scrotum in an older
      adult in a nursing home".

PMID- 23148435
TI  - 2012 updated Beers Criteria: greater applicability to Europe?

PMID- 23148437
TI  - Credulous fondness for celecoxib.

PMID- 23148439
TI  - Response to Gerogeriatrics.

PMID- 23148441
TI  - Total syntheses of naturally occurring seimatopolide A and its enantiomer from
      chiral pool starting materials using a bidirectional strategy.
AB  - Enantioselective total syntheses of both enantiomers of the recently isolated
      decanolide natural product seimatopolide A are described. The C(2)-symmetric
      building blocks (R,R)-hexa-1,5-diene-3,4-diol (derived from D-mannitol) and its
      enantiomer (derived from l-(+)-tartrate) serve as key starting materials, which
      are elaborated in a bidirectional way using a selective mono-cross-metathesis,
      regio- and stereoselective epoxidation, and regioselective reductive epoxide
      opening to furnish the first fragment. Both enantiomers of the second fragment, 3
      hydroxypent-4-enoic acid, were conveniently obtained through a lipase-catalyzed
      kinetic resolution and merged with the first fragment via Shiina esterification.
      An E-selective ring-closing metathesis was used to access the 10-membered
      lactone. A comparison of the specific optical rotations of synthetic
      seimatopolides with those reported for the natural product suggests that the
      originally assigned (3R,6R,7R,9S)-configuration should be corrected to
      (3S,6S,7S,9R).

PMID- 23148442
TI  - Effect of masked hypertension on aortic elastic properties.
AB  - Aortic stiffness is increased in patients with sustained hypertension (SH). The
      aim of this study was to investigate the relationship between aortic elastic
      properties and masked hypertension (MH). We evaluated aortic elastic properties
      in 35 individuals with MH, 35 patients with SH, and 35 normotensive healthy
      volunteers using transthoracic Doppler echocardiography. All aortic
      distensibility values were carried out at the same time or immediately after the
      blood pressure (BP) measurement. Baseline clinical and demographic
      characteristics of the patients were similar in all three groups. Aortic
      stiffness index and elastic modulus values were higher in MH group compared to SH
      group and control group (8.9 +/- 6.3 vs. 5.4 +/- 2.2 vs. 4.2 +/- 2.5, P < .001
      and 9.0 +/- 6.3 vs. 6.4 +/- 2.5 vs. 4.1 +/- 2.4, P < .001, respectively). Aortic
      strain values were lower in MH group compared to SH group and control group (7.4
      +/- 5.3 vs. 9.5 +/- 4.1 vs. 14.6 +/- 7.1, P < .001, respectively). Aortic
      distensibility values were lower in MH and SH groups compared to controls (3.1 +/
      1.9 vs. 3.7 +/- 1.6 vs. 6.4 +/- 3.4, P < .001, respectively). Furthermore,
      diastolic aortic diameter, left ventricular mass index, interventricular septum,
      and posterior wall thickness were higher in MH and SH groups when compared to
      controls. This study shows that masked hypertensive patients are at higher risk
      of "aortic" stiffness, a risk factor for cardiovascular morbidity and mortality,
      than normotensive and sustained hypertensive patients.

PMID- 23148443
TI  - Venomic and transcriptomic analysis of centipede Scolopendra subspinipes dehaani.
AB  - Centipedes have venom glands in their first pair of limbs, and their venoms
      contain a large number of components with different biochemical and
      pharmacological properties. However, information about the compositions and
      functions of their venoms is largely unknown. In this study, Scolopendra
      subspinipes dehaani venoms were systematically investigated by transcriptomic and
      proteomic analysis coupled with biological function assays. After random
      screening approximately 1500 independent clones, 1122 full length cDNA sequences,
      which encode 543 different proteins, were cloned from a constructed cDNA library
      using a pair of venom glands from a single centipede species. Neurotoxins, ion
      channel acting components and venom allergens were the main fractions of the
      crude venom as revealed by transcriptomic analysis. Meanwhile, 40
      proteins/peptides were purified and characterized from crude venom of S.
      subspinipes dehaani. The N-terminal amino acid sequencing and mass spectrum
      results of 29 out of these 40 proteins or peptides matched well with their
      corresponding cDNAs. The purified proteins/peptides showed different
      pharmacological properties, including the following: (1) platelet aggregating
      activity; (2) anticoagulant activity; (3) phospholipase A(2) activity; (4)
      trypsin inhibiting activity; (5) voltage-gated potassium channel activities; (6)
      voltage-gated sodium channel activities; (7) voltage-gated calcium channel
      activities. Most of them showed no significant similarity to other protein
      sequences deposited in the known public database. This work provides the largest
      number of protein or peptide candidates with medical-pharmaceutical significance
      and reveals the toxin nature of centipede S. subspinipes dehaani venom.

PMID- 23148445
TI  - Culturomics: a new approach to study the human microbiome.

PMID- 23148444
TI  - Pleomorphic lipoma lacking mature fat component in extensive myxoid stroma: a
      great diagnostic challenge.
AB  - Pleomorphic lipoma is a relatively uncommon entity, and is considered as a
      variant of spindle cell lipoma. Histologically, spindle cell lipoma/pleomorphic
      lipoma consists of varying quantity of mature fat, bland spindle cells and ropey
      collagen. In addition, pleomorphic lipoma is characterized by multinucleate giant
      cells, which possess the "floret-like" nuclei and marked pleomorphism. So, in
      contrast to spindle cell lipoma, pleomorphic lipoma is more easily misdiagnosed
      as a malignant tumor. Herein, we report a peculiar case of pleomorphic lipoma
      occurring in axilla with entirely devoid of mature fat in a 71-year-old male. The
      histopathological findings demonstrated the tumor was made up of bland spindle
      cells admixed with scattered "floret-like" cells and irregular ropey collagen in
      an extensive myxoid stroma. Immunostaining showed that the tumor was positive for
      the Vimentin, Bcl-2 and CD34, and was negative for S-100, desmin, CD68, and alpha
      SMA. Although no fat component was found in the whole section, the tumor was
      still diagnosed as a pelomprphic lipoma. To our knowledge, this is the third
      reported case of pelomprphic lipoma which entirely lacked lipomatous component.
      Because of the existence of atypical multinucleate giant cells and lack of mature
      fat, this tumor may be easily misdiagnosed nonlipomatous lesions, such as myxoid
      fibrosarcoma, giant cell fibroblastoma. So, it is necessary to pay careful
      attention to the histological spectrum of pleomorphic lipoma, including the tumor
      with devoid of fat, and it should be kept in mind that pelomprphic lipoma still
      can be diagnosed even if lacking lipomatous component. VIRTUAL SLIDES: The
      virtual slide(s) for this article can be found here:
      http://www.diagnosticpathology.diagnomx.eu/vs/1967123180611361.

PMID- 23148446
TI  - Orthopaedic device-associated infection.

PMID- 23148447
TI  - The role of molecular diagnostics in implant-associated bone and joint infection.
AB  - Microbiological culture is the conventional method for establishing the diagnosis
      in implant-associated bone and joint infection, but it may lack both specificity
      and sensitivity. Molecular diagnosis has been an important step in the diagnosis
      of infectious diseases. We review the principles and the role of molecular
      diagnosis in improving the aetiological diagnosis of implant-associated bone and
      joint infection. Currently, molecular diagnosis mainly includes conventional
      broad-range PCR and specific PCR assays. These tools are efficient, but several
      pitfalls exist that necessitate rigour in all steps of the process. In implant
      associated bone and joint infection, molecular assays have been shown to be
      useful in complementing culture techniques to identify microorganisms when
      patients have previously received antibiotics or in the presence of fastidious
      microorganisms. Broad-range PCR targeting the 16S rRNA sequence followed by
      sequencing must be performed in culture-negative specimens when infection is
      suspected on the basis of clinical signs and symptoms or inflammatory syndrome.
      This molecular tool has allowed not only increasing identification of anaerobic
      bacteria, such as Finegoldia magna, but also the discovery of the role of
      Tropheryma whipplei, an aetiological agent of implant-associated bone and joint
      infection in patients without Whipple's disease. Real-time pathogen-specific PCR
      assays performed in a closed system are more sensitive and specific than broad
      range PCR, but each assay is typically able to detect only a single
      microorganism. These assays should be performed to confirm the identification
      provided by broad-spectrum PCR, and also when broad-range PCR fails to detect a
      microorganism despite efficient DNA extraction.

PMID- 23148449
TI  - Prices need no preferences: social trends determine decisions in experimental
      markets for pain relief.
AB  - OBJECTIVE: A standard view in health economics is that, although there is no
      market that determines the "prices" for health states, people can nonetheless
      associate health states with monetary values (or other scales, such as quality
      adjusted life year [QALYs] and disability adjusted life year [DALYs]). Such
      valuations can be used to shape health policy, and a major research challenge is
      to elicit such values from people; creating experimental "markets" for health
      states is a theoretically attractive way to address this. We explore the
      possibility that this framework may be fundamentally flawed-because there may not
      be any stable values to be revealed. Instead, perhaps people construct ad hoc
      values, influenced by contextual factors, such as the observed decisions of
      others. METHOD: The participants bid to buy relief from equally painful
      electrical shocks to the leg and arm in an experimental health market based on an
      interactive second-price auction. Thirty subjects were randomly assigned to two
      experimental conditions where the bids by "others" were manipulated to follow
      increasing or decreasing price trends for one, but not the other, pain. After the
      auction, a preference test asked the participants to choose which pain they
      prefer to experience for a longer duration. RESULTS: Players remained indifferent
      between the two pain-types throughout the auction. However, their bids were
      differentially attracted toward what others bid for each pain, with overbidding
      during decreasing prices and underbidding during increasing prices. CONCLUSION:
      Health preferences are dissociated from market prices, which are strongly
      referenced to others' choices. This suggests that the price of health care in a
      free-market has the capacity to become critically detached from people's
      underlying preferences.

PMID- 23148450
TI  - A prospective investigation of the relationships between self-presentation
      processes and physical activity in women treated for breast cancer.
AB  - OBJECTIVES: In the current study, we (a) describe naturally occurring changes in
      self-presentation processes (i.e., impression motivation, impression
      construction) and moderate-to-vigorous intensity physical activity (MVPA) over a
      period of 6 months among women who were treated for breast cancer; (b) evaluate
      the associations of cancer-specific factors with self-presentation processes and
      MVPA; and (c) examine the within- and between-person associations of self
      presentation processes with MVPA. METHOD: For this prospective longitudinal
      study, women (n = 128; Mage = 55.14 years) completed questionnaires posttreatment
      for breast cancer (Mtime since treatment = 3.96 months), as well as 3 and 6
      months later. RESULTS: Based on the findings of the multilevel analysis, self
      presentation processes remained stable over time, whereas MVPA levels changed
      over time (Blinear = 6.11, SE = 2.44, Bquadratic = -3.41, SE = 1.23).
      Radiotherapy was related to impression motivation (B = -.40, SE = .19) and
      impression construction (B = -.45, SE = .15), and chemotherapy was related to
      impression motivation (B = .31, SE = .15). Impression motivation was associated
      with MVPA at the between-person level (gamma01 = 5.72, SE = 1.22), and impression
      construction was associated with MVPA at the between- and within-person levels
      (gamma01 = 3.45, SE = 1.49; gamma10 = 3.67, SE = 1.66). CONCLUSIONS: This study
      provides insight into the patterns of self-presentation processes and MVPA during
      early cancer survivorship, as well as the associations between these constructs
      at the within- and between-person levels. Based on these findings, more research
      is needed to determine whether self-presentation processes should be
      conceptualized as state or trait characteristics or as having both components,
      and extend the self-presentation framework to incorporate additional explanatory
      variables as this might provide a more complete explanation of MVPA.

PMID- 23148454
TI  - Simulation of bone remodelling in orthodontic treatment.
AB  - Orthodontic treatments not only displace irregular teeth but also induce
      responses in surrounding bone tissues. Bone remodelling is regarded as the
      regulatory mechanism triggered by mechanical loading. This study was aimed at
      investigating the effect of orthodontic loading on both tooth movement and
      neighbouring bone density distribution. A set of computational algorithms
      incorporating both external and internal remodelling mechanisms was implemented
      into a patient-specific 3D finite element (FE) model to investigate and analyse
      orthodontic treatment under four typical modes of orthodontic loading. The
      consequence of orthodontic treatment was reproduced numerically by using this FE
      based technique. The results indicated that the diverse modes of orthodontic
      loading would result in different magnitudes of tooth movement and particular
      morphology of bone density distribution. It is illuminated that the newly
      developed algorithms may replicate the clinical situation more closely compared
      with the previous proposed method. 

PMID- 23148451
TI  - Economic adversity and children's sleep problems: multiple indicators and
      moderation of effects.
AB  - OBJECTIVE: Toward explicating relations between economic adversity and children's
      sleep, we examined associations between multiple indicators of socioeconomic
      status (SES)/adversity and children's objectively and subjectively derived sleep
      parameters; ethnicity was examined as potential moderator. METHODS: Participants
      were 276 third- and fourth-grade children and their families (133 girls; M age =
      9.44 years; SD = .71): 66% European American (EA) and 34% African American (AA).
      Four SES indicators were used: income-to-needs ratio, perceived economic well
      being, maternal education, and community poverty. Children wore actigraphs for 7
      nights and completed a self-report measure to assess sleep problems. RESULTS:
      Objectively and subjectively assessed sleep parameters were related to different
      SES indicators, and overall worse sleep was evident for children from lower SES
      homes. Specifically, children from homes with lower income-to-needs ratios had
      higher levels of reported sleep/wake problems. Parental perceived economic well
      being was associated with shorter sleep minutes and greater variability in sleep
      onset for children. Lower mother's education was associated with lower sleep
      efficiency. Children who attended Title 1 schools had shorter sleep minutes.
      Ethnicity was a significant moderator of effects in the link between some SES
      indicators and children's sleep. AA children's sleep was more negatively affected
      by income-to-needs ratio and mother's education than was the sleep of EA
      children. CONCLUSIONS: The results advocate for the importance of specifying
      particular SES and sleep variables used because they may affect the ability to
      detect associations between sleep and economic adversity.

PMID- 23148455
TI  - The influence of affective states on the process of lie detection.
AB  - Lay theories about the tell tale signs of deception include numerous nonverbal
      cues; empirically, however, a focus on message content results in better lie
      detection than a focus on nonverbal elements. Feelings-as-information theory
      (Schwarz, 1990, 2012) predicts that systematic processing of message content is
      more likely under sad than happy moods, whereas reliance on salient cues is more
      likely under happy than sad moods. If so, perceivers who are asked to evaluate
      the veracity of a message should (a) attend more to message content when they are
      in a negative mood, but (b) more to nonverbal cues when they are in a positive
      mood. This should (c) result in more accurate identification of true as well as
      false messages under sad mood, mediated by (d) mood-induced differences in
      processing style. Three experiments tested these predictions. In Experiments 1
      and 2, participants in a negative mood achieved higher accuracy in classifying
      truthful as well as deceptive messages than participants in a positive mood.
      Experiment 3 crossed nonverbal cues (fidgety vs. calm movements) and message
      characteristics (low vs. high plausibility). Only the plausibility of the message
      influenced participants' credibility judgments under sad mood conditions, whereas
      only the nonverbal cues influenced participants' judgments of credibility under
      happy mood conditions. Implications for lie detection and the interplay of
      feeling and thinking are discussed.

PMID- 23148456
TI  - Study protocol for the Integra Initiative to assess the benefits and costs of
      integrating sexual and reproductive health and HIV services in Kenya and
      Swaziland.
AB  - BACKGROUND: In sub-Saharan Africa (SSA) there are strong arguments for the
      provision of integrated sexual and reproductive health (SRH) and HIV services.
      Most HIV transmissions are sexually transmitted or associated with pregnancy,
      childbirth, and breastfeeding. Many of the behaviours that prevent HIV
      transmission also prevent sexually transmitted infections and unintended
      pregnancies. There is potential for integration to increase the coverage of HIV
      services, as individuals who use SRH services can benefit from HIV services and
      vice-versa, as well as increase cost-savings. However, there is a dearth of
      empirical evidence on effective models for integrating HIV/SRH services. The need
      for robust evidence led a consortium of three organizations - International
      Planned Parenthood Federation, Population Council and the London School of
      Hygiene & Tropical Medicine - to design/implement the Integra Initiative. Integra
      seeks to generate rigorous evidence on the feasibility, effectiveness, cost and
      impact of different models for delivering integrated HIV/SRH services in high and
      medium HIV prevalence settings in SSA. METHODS/DESIGN: A quasi-experimental study
      will be conducted in government clinics in Kenya and Swaziland - assigned into
      intervention/comparison groups. Two models of service delivery are investigated:
      integrating HIV care/treatment into 1) family planning and 2) postnatal care. A
      full economic-costing will be used to assess the costs of different components of
      service provision, and the determinants of variations in unit costs across
      facilities/service models. Health facility assessments will be conducted at four
      time-periods to track changes in quality of care and utilization over time. A two
      year cohort study of family planning/postnatal clients will assess the effect of
      integration on individual outcomes, including use of SRH services, HIV status
      (known/unknown) and pregnancy (planned/unintended). Household surveys within some
      of the study facilities' catchment areas will be conducted to profile users/non
      users of integrated services and demand/receipt of integrated services, before
      and-after the intervention. Qualitative research will be conducted to complement
      the quantitative component at different time points. Integra takes an embedded
      'programme science' approach to maximize the uptake of findings into
      policy/practice. DISCUSSION: Integra addresses existing evidence gaps in the
      integration evaluation literature, building on the limited evidence from SSA and
      the expertise of its research partners. TRIAL REGISTRATION: Current Controlled
      Trials NCT01694862.

PMID- 23148457
TI  - Lack of subjective tendency to bleed as clinical marker for aspirin resistance.

PMID- 23148459
TI  - Optimizing global health experiences in emergency medicine residency programs: a
      consensus statement from the Council of Emergency Medicine Residency Directors
      2011 Academic Assembly global health specialty track.
AB  - BACKGROUND: An increasing number of emergency medicine (EM) residency training
      programs have residents interested in participating in clinical rotations in
      other countries. However, the policies that each individual training program
      applies to this process are different. To our knowledge, little has been done in
      the standardization of these experiences to help EM residency programs with the
      evaluation, administration and implementation of a successful global health
      clinical elective experience. The objective of this project was to assess the
      current status of EM global health electives at residency training programs and
      to establish recommendations from educators in EM on the best methodology to
      implement successful global health electives. METHODS: During the 2011 Council of
      Emergency Medicine Residency Directors (CORD) Academic Assembly, participants met
      to address this issue in a mediated discussion session and working group. Session
      participants examined data previously obtained via the CORD online listserve,
      discussed best practices in global health applications, evaluations and
      partnerships, and explored possible solutions to some of the challenges. In
      addition a survey was sent to CORD members prior to the 2011 Academic Assembly to
      evaluate the resources and processes for EM residents' global experiences.
      RESULTS: Recommendations included creating a global health working group within
      the organization, optimizing a clearinghouse of elective opportunities for
      residents and standardizing elective application materials, site evaluations and
      resident assessment/feedback methods. The survey showed that 71.4% of respondents
      have global health partnerships and electives. However, only 36.7% of programs
      require pre-departure training, and only 20% have formal competency requirements
      for these global health electives. CONCLUSIONS: A large number of EM training
      programs have global health experiences available, but these electives and the
      trainees may benefit from additional institutional support and formalized
      structure.

PMID- 23148458
TI  - Shared decision making for prostate cancer screening: the results of a combined
      analysis of two practice-based randomized controlled trials.
AB  - BACKGROUND: Professional societies recommend shared decision making (SDM) for
      prostate cancer screening, however, most efforts have promoted informed rather
      than shared decision making. The objective of this study is to 1) examine the
      effects of a prostate cancer screening intervention to promote SDM and 2)
      determine whether framing prostate information in the context of other clearly
      beneficial men's health services affects decisions. METHODS: We conducted two
      separate randomized controlled trials of the same prostate cancer intervention
      (with or without additional information on more clearly beneficial men's health
      services). For each trial, we enrolled a convenience sample of 2 internal
      medicine practices, and their interested physicians and male patients with no
      prior history of prostate cancer (for a total of 4 practices, 28 physicians, and
      128 men across trials). Within each practice site, we randomized men to either 1)
      a video-based decision aid and researcher-led coaching session or 2) a highway
      safety video. Physicians at each site received a 1-hour educational session on
      prostate cancer and SDM. To assess intervention effects, we measured key
      components of SDM, intent to be screened, and actual screening. After finding
      that results did not vary by trial, we combined data across sites, adjusting for
      the random effects of both practice and physician. RESULTS: Compared to an
      attention control, our prostate cancer screening intervention increased men's
      perceptions that screening is a decision (absolute difference +41%; 95% CI 25 to
      57%) and men's knowledge about prostate cancer screening (absolute difference
      +34%; 95% CI 19% to 50%), but had no effect on men's self-reported participation
      in shared decisions or their participation at their preferred level. Overall, the
      intervention decreased screening intent (absolute difference -34%; 95% CI -50% to
      -18%) and actual screening rates (absolute difference -22%; 95% CI -38 to -7%)
      with no difference in effect by frame. CONCLUSIONS: SDM interventions can
      increase men's knowledge, alter their perceptions of prostate cancer screening,
      and reduce actual screening. However, they may not guarantee an increase in
      shared decisions. TRIAL REGISTRATION: #NCT00630188.

PMID- 23148460
TI  - Multi-walled carbon nanotube-induced inflammatory response and oxidative stress 
      in a dynamic cell growth environment.
AB  - BACKGROUND: Rapid increase in multi-walled carbon nanotube (MWCNT) production
      for their industrial and biomedical applications has led to concerns over the
      effects of MWCNTs on human health and the environment. Both animal and in vitro
      studies have provided important findings about MWCNT-induced effects on the lung
      cells or tissues. In vitro studies have provided a considerable amount of
      fundamental information on MWCNT-induced effects on the specific lung cells.
      However, the cell culture systems used in those studies were limited by the
      absence of dynamic nature of lung tissues. We hypothesized that MWCNT-induced
      cellular responses such as proliferation, inflammation, and oxidative stress
      under dynamic cell growth environment may differ from those under static cell
      growth environment. RESULTS: In this study, we used a dynamic cell growth
      condition to mimic mechanically dynamic environment of the lung and characterized
      interleukin 8 (IL-8), reactive oxygen species (ROS), glutathione (GSH), and cell
      proliferation for three days following exposure of MWCNTs at different
      concentrations (5, 10, and 20 MUg/ml) to A549 cell monolayer under both static
      and dynamic cell growth conditions. Our results demonstrated the distinct
      differences in the levels of inflammatory response and oxidative stress between
      static and dynamic cell growth conditions. CONCLUSIONS: In conclusion, the
      dynamic cell growth system used in this study provided important changes in
      cellular responses that were not found in the static cell growth system and were
      similar to animal studies. The dynamic cell growth system can be considered as a
      viable alternative to in vivo test system in combination with existing in vitro
      static cell growth systems to evaluate the effect of MWCNTs on cellular responses
      in the respiratory system.

PMID- 23148461
TI  - Catalytic desymmetrization of cyclohexadienes by asymmetric bromolactonization.
AB  - Asymmetric bromolactonization of prochiral cyclohexadiene derivatives with N
      bromosuccimide proceeded in the presence of (DHQD)(2)PHAL as a chiral catalyst to
      afford the corresponding bromolactones with up to 93% ee. This reaction was also
      applicable to the kinetic resolution of a racemic cyclic ene-carboxylic acid,
      where the starting material was recovered with high enantioselectivity.

PMID- 23148463
TI  - g-B3N3C: a novel two-dimensional graphite-like material.
AB  - : A novel crystalline structure of hybrid monolayer hexagonal boron nitride
      (BN) and graphene is predicted by means of the first-principles calculations.
      This material can be derived via boron or nitrogen atoms which are substituted by
      carbon atoms evenly in the graphitic BN with vacancies. The corresponding
      structure is constructed from a BN hexagonal ring linking an additional carbon
      atom. The unit cell is composed of seven atoms, three of which are boron atoms,
      three are nitrogen atoms, and one is a carbon atom. It shows a similar space
      structure as graphene, which is thus coined as g-B3N3C. Two stable topological
      types associated with the carbon bond formation, i.e., C-N or C-B bonds, are
      identified. Interestingly, distinct ground states of each type, depending on C-N
      or C-B bonds, and electronic bandgap as well as magnetic properties within this
      material have been studied systematically. Our work demonstrates a practical and
      efficient access to electronic properties of two-dimensional nanostructures,
      providing an approach to tackling open fundamental questions in bandgap
      engineered devices and spintronics.

PMID- 23148462
TI  - MAPK-dependent JA and SA signalling in Nicotiana attenuata affects plant growth
      and fitness during competition with conspecifics.
AB  - BACKGROUND: Induced defense responses to herbivores are generally believed to
      have evolved as cost-saving strategies that defer the fitness costs of defense
      metabolism until these defenses are needed. The fitness costs of jasmonate (JA)
      mediated defenses have been well documented. Those of the early signaling units
      mediating induced resistance to herbivores have yet to be examined. Early
      signaling components that mediate herbivore-induced defense responses in
      Nicotiana attenuata, have been well characterized and here we examine their
      growth and fitness costs during competition with conspecifics. Two mitogen
      activated protein kinases (MAPKs), salicylic acid (SA)-induced protein kinase
      (SIPK) and wound-induced protein kinase (WIPK) are rapidly activated after
      perception of herbivory and both kinases regulate herbivory-induced JA levels and
      JA-mediated defense metabolite accumulations. Since JA-induced defenses result in
      resource-based trade-offs that compromise plant productivity, we evaluated if
      silencing SIPK (irSIPK) and WIPK (irWIPK) benefits the growth and fitness of
      plants competiting with wild type (WT) plants, as has been shown for plants
      silenced in JA-signaling by the reduction of Lipoxygenase 3 (LOX3) levels.
      RESULTS: As expected, irWIPK and LOX3-silenced plants out-performed their
      competing WT plants. Surprisingly, irSIPK plants, which have the largest
      reductions in JA signaling, did not. Phytohormone profiling of leaves revealed
      that irSIPK plants accumulated higher levels of SA compared to WT. To test the
      hypothesis that these high levels of SA, and their presumed associated fitness
      costs of pathogen associated defenses in irSIPK plants had nullified the JA
      deficiency-mediated growth benefits in these plants, we genetically reduced SA
      levels in irSIPK plants. Reducing SA levels partially recovered the biomass and
      fitness deficits of irSIPK plants. We also evaluated whether the increased
      fitness of plants with reduced SA or JA levels resulted from increased nitrogen
      or CO2 assimilation rates, and found no evidence that greater intake of these
      fitness-limiting resources were responsible. CONCLUSIONS: Signaling mediated by
      WIPK, but not SIPK, is associated with large fitness costs in competing N.
      attenuata plants, demonstrating the contrasting roles that these two MAPKs play
      in regulating the plants' growth-defense balance. We discuss the role of SIPK as
      an important regulator of plant fitness, possibly by modulating SA-JA crosstalk
      as mediated through ethylene signaling.

PMID- 23148464
TI  - Forgetting our personal past: socially shared retrieval-induced forgetting of
      autobiographical memories.
AB  - People often talk to others about their personal past. These discussions are
      inherently selective. Selective retrieval of memories in the course of a
      conversation may induce forgetting of unmentioned but related memories for both
      speakers and listeners (Cuc, Koppel, & Hirst, 2007). Cuc et al. (2007) defined
      the forgetting on the part of the speaker as within-individual retrieval-induced
      forgetting (WI-RIF) and the forgetting on the part of the listener as socially
      shared retrieval-induced forgetting (SS-RIF). However, if the forgetting
      associated with WI-RIF and SS-RIF is to be taken seriously as a mechanism that
      shapes both individual and shared memories, this mechanism must be demonstrated
      with meaningful material and in ecologically valid groups. In our first 2
      experiments we extended SS-RIF from unemotional, experimenter-contrived material
      to the emotional and unemotional autobiographical memories of strangers
      (Experiment 1) and intimate couples (Experiment 2) when merely overhearing the
      speaker selectively practice memories. We then extended these results to the
      context of a free-flowing conversation (Experiments 3 and 4). In all 4
      experiments we found WI-RIF and SS-RIF regardless of the emotional valence or
      individual ownership of the memories. We discuss our findings in terms of the
      role of conversational silence in shaping both our personal and shared pasts.

PMID- 23148465
TI  - Color preferences are not universal.
AB  - Claims of universality pervade color preference research. It has been argued that
      there are universal preferences for some colors over others (e.g., Eysenck,
      1941), universal sex differences (e.g., Hurlbert & Ling, 2007), and universal
      mechanisms or dimensions that govern these preferences (e.g., Palmer & Schloss,
      2010). However, there have been surprisingly few cross-cultural investigations of
      color preference and none from nonindustrialized societies that are relatively
      free from the common influence of global consumer culture. Here, we compare the
      color preferences of British adults to those of Himba adults who belong to a
      nonindustrialized culture in rural Namibia. British and Himba color preferences
      are found to share few characteristics, and Himba color preferences display none
      of the so-called "universal" patterns or sex differences. Several significant
      predictors of color preference are identified, such as cone-contrast between
      stimulus and background (Hurlbert & Ling, 2007), the valence of color-associated
      objects (Palmer & Schloss, 2010), and the colorfulness of the color. However, the
      relationship of these predictors to color preference was strikingly different for
      the two cultures. No one model of color preference is able to account for both
      British and Himba color preferences. We suggest that not only do patterns of
      color preference vary across individuals and groups but the underlying mechanisms
      and dimensions of color preference vary as well. The findings have implications
      for broader debate on the extent to which our perception and experience of color
      is culturally relative or universally constrained.

PMID- 23148466
TI  - Identifying change in the likelihood of violent recidivism: causal dynamic risk
      factors in the OASys violence predictor.
AB  - Recent studies of multiwave risk assessment have investigated the association
      between changes in risk factors and violent recidivism. This study analyzed a
      large multiwave data set of English and Welsh offenders (N = 196,493), assessed
      in realistic correctional conditions using the static/dynamic Offender Assessment
      System (OASys). It aimed to compare the predictive validity of the OASys Violence
      Predictor (OVP) under mandated repeated assessment and one-time initial
      assessment conditions. Scores on 5 of OVP's 7 purportedly dynamic risk factors
      changed in 6 to 15% of pairs of successive assessments, whereas the other 2
      seldom changed. Violent reoffenders had higher initial total and dynamic OVP
      scores than nonreoffenders, yet nonreoffenders' dynamic scores fell by
      significantly more between initial and final assessment. OVP scores from the
      current assessment achieved greater predictive validity than those from the
      initial assessment. Cox regression models showed that, for total OVP scores and
      most risk factors, both the initial score and the change in score from initial to
      current assessment significantly predicted reoffending. These results
      consistently showed that OVP includes several causal dynamic risk factors for
      violent recidivism, which can be measured reliably in operational settings. This
      adds to the evidence base that links changes in risk factors to changes in future
      reoffending risk and links the use of repeated assessments to incremental
      improvements in predictive validity. Further research could quantify the costs
      and benefits of reassessment in correctional practice, study associations between
      treatment and dynamic risk factors, and separate the effects of improvements and
      deteriorations in dynamic risk.

PMID- 23148467
TI  - Competency to stand trial among female inpatients.
AB  - Competency to stand trial evaluations are conducted by forensic mental health
      professionals to opine whether defendants possess the mental abilities to
      understand, appreciate, and reason in regard to their court proceedings. The
      majority of research on competency to stand trial evaluations has focused on
      males, with research on female defendants being relatively underexplored. Even
      less is known of diverse female samples referred for competency evaluation. In
      the current study, we sought to examine whether characteristics associated with
      competency among predominantly male samples translate to a racially, ethnically,
      and culturally diverse group of female defendants (N = 288, 85% non-White). Chi
      square analyses revealed significant relationships between findings of
      incompetence and defendants' diagnosis of a psychotic disorder, active psychotic
      symptoms, medication noncompliance, nonparticipation in the evaluation, and
      nonfelony charges. Logistic regression analysis indicated that defendants who
      experienced active psychotic symptoms, did not participate in their evaluations,
      and were not compliant with their medication were most likely to be found
      incompetent. Notably, neither minority status nor age was a significant
      characteristic in predicting incompetence. These findings in particular differ
      from much of the literature and highlight the need to examine competency within a
      cross-cultural framework, as characteristics associated with competency opinions
      do not necessarily translate across demographic groups.

PMID- 23148468
TI  - Speaker identity supports phonetic category learning.
AB  - Visual cues from the speaker's face, such as the discriminable mouth movements
      used to produce speech sounds, improve discrimination of these sounds by adults.
      The speaker's face, however, provides more information than just the mouth
      movements used to produce speech--it also provides a visual indexical cue of the
      identity of the speaker. The current article examines the extent to which there
      is separable encoding of speaker identity in speech processing and asks whether
      speech discrimination is influenced by speaker identity. Does consistent pairing
      of different speakers' faces with different sounds--that is, hearing one speaker
      saying one sound and a second speaker saying the second sound--influence the
      brain's discrimination of the sounds? ERP data from participants previously
      exposed to consistent speaker-sound pairing indicated improved detection of the
      phoneme change relative to participants previously exposed to inconsistent
      speaker-sound pairing--that is, hearing both speakers say both sounds. The
      results strongly suggest an influence of visual speaker identity in speech
      processing.

PMID- 23148470
TI  - Bimanual interference associated with handling different tool transformations.
AB  - Research on bimanual coordination of hand movements has identified several loci
      of bimanual interference, including interference because of programming different
      movement parameters or selecting different targets for the two hands. This study
      investigates the extent and origin of interference when participants execute
      bimanual actions with tools. In the experiments, participants moved two tools,
      one with each hand, to two directly cued target locations. One type of tool
      transformed the body movement into a spatially compatible movement of the
      effective part of the tool, whereas the other transformed it into a spatially
      incompatible movement. Tool transformations for the two hands were either the
      same or different. Furthermore, target locations were either in the same or in
      different spatial directions. Results indicated significantly shorter reaction
      times (RTs) and less errors when tool transformations were the same for both
      hands. In addition, movements were initiated more quickly and less error-prone
      when targets were in the same direction, but this effect was modulated by the
      congruency of the two lever transformations. Investigations of the time course of
      the effects revealed that they were not because of early perceptual processing
      (Experiment 2). Furthermore, the general pattern of results occurred for
      different grip positions (Experiment 3) and different lever types (Experiment 4),
      suggesting that it reflects rather general constraints in bimanual coordination
      of tool-use actions.

PMID- 23148469
TI  - Similar response patterns do not imply identical origins: an energetic masking
      account of nonspeech effects in compensation for coarticulation.
AB  - Nonspeech materials are widely used to identify basic mechanisms underlying
      speech perception. For instance, they have been used to examine the origin of
      compensation for coarticulation, the observation that listeners' categorization
      of phonetic segments depends on neighboring segments (Mann, 1980). Specifically,
      nonspeech precursors matched to critical formant frequencies of speech precursors
      have been shown to produce similar categorization shifts as speech contexts. This
      observation has been interpreted to mean that spectrally contrastive frequency
      relations between neighboring segments underlie the categorization shifts
      observed after speech, as well as nonspeech precursors (Lotto & Kluender, 1998).
      From the gestural perspective, however, categorization shifts in speech contexts
      occur because of listeners' sensitivity to acoustic information for
      coarticulatory gestural overlap in production; in nonspeech contexts, this occurs
      because of energetic masking of acoustic information for gestures. In 2
      experiments, we distinguish the energetic masking and spectral contrast accounts.
      In Experiment 1, we investigated the effects of varying precursor tone frequency
      on speech categorization. Consistent only with the masking account, tonal effects
      were greater for frequencies close enough to those in the target syllables for
      masking to occur. In Experiment 2, we filtered the target stimuli to simulate
      effects of masking and obtained behavioral outcomes that closely resemble those
      with nonspeech tones. We conclude that masking provides the more plausible
      account of nonspeech context effects. More generally, we suggest that similar
      results from the use of speech and nonspeech materials do not automatically imply
      identical origins and that the use of nonspeech in speech studies entails careful
      examination of the nature of information in the nonspeech materials.

PMID- 23148471
TI  - Multiple bottlenecks in hierarchical control of action sequences: what does
      "response selection" select in skilled typewriting?
AB  - Does response selection select words or letters in skilled typewriting? Typing
      performance involves hierarchically organized control processes: an outer loop
      that controls word level processing, and an inner loop that controls letter (or
      keystroke) level processing. The present study addressed whether response
      selection occurs in the outer loop or the inner loop by using the psychological
      refractory period (PRP) paradigm in which Task1 required typing single words and
      Task2 required vocal responses to tones. The number of letters (string length) in
      the words was manipulated to discriminate selection of words from selection of
      keystrokes. In Experiment 1, the PRP effect depended on string length of words in
      Task1, suggesting that response selection occurs in the inner loop. To assess
      contributions of the outer loop, the influence of string length was examined in a
      lexical-decision task that also involves word encoding and lexical access
      (Experiment 2), or to-be-typed words were preexposed so outer-loop processing
      could finish before typing started (Experiment 3). Response time for Task2 (RT2)
      did not depend on string length with lexical decision, and RT2 still depended on
      string length with typing preexposed strings. These results support the inner
      loop locus of the PRP effect. In Experiment 4, typing was performed as Task2, and
      the effect of string length on typing RT interacted with stimulus onset
      asynchrony superadditively, implying that another bottleneck also exists in the
      outer loop. We conclude that there are at least two bottleneck processes in
      skilled typewriting.

PMID- 23148472
TI  - The highs and lows of the interaction between word meaning and space.
AB  - We examined whether the processing of words associated with distinct spatial
      locations automatically biases behavior toward these locations in space. In four
      experiments (Ns = 30, 34, 32, 32), participants were shown stimuli denoting
      objects typically associated with the upper and lower regions of visual space. In
      Experiment 1, words were categorized as man-made or natural by pressing one of
      two vertically arranged keys. Reaction times were faster for trials in which
      response locations were congruent with the stimulus-associated locations.
      Experiment 2 replicated the stimulus-response congruency effect when the stimuli
      were presented in a pictorial format. Stimuli-space interactions therefore seem
      to be driven by an automatic activation of the spatial attributes associated with
      the stimuli, irrespective of input format. In Experiments 3 and 4, a target
      detection task involving only one response button was employed to examine whether
      the effects observed in the first two experiments were due to attentional shifts,
      independent of response selection processes. In both experiments, the previously
      observed congruence effect between words and space either diminished or vanished
      completely. Consequently, the results of the four experiments in the current
      study point to a dominant role of response-selection processes in the genesis of
      space-object word interactions.

PMID- 23148473
TI  - Relative change probability affects the decision process of detecting multiple
      feature changes.
AB  - Change in a real world setting usually consists of multiple feature changes, and
      one feature may change more often than another. This study manipulated the number
      of changes in orientation and spatial frequency to examine the effect of the
      relative change probability on the comparison and decision processes in a change
      detection task. Results showed that when two types of features changed equally
      often (Experiment 1), parallel self-terminating processing was adopted. When
      frequency changed more often than orientation (Experiment 2), serial self
      terminating processing was adopted. However, when there was a lack of cognitive
      resources (Experiment 3), parallel self-terminating processing was adopted even
      when relative saliency existed. In all three experiments, the process capacity
      ranged from limited to unlimited. In addition, the participants reported that
      they were not aware of their use of change probability information, thus,
      providing evidence of implicit learning of change probability. These results
      support the relative saliency hypothesis: relative change probability affects the
      relative salience between features and, consequently, influences the adoption of
      decision strategies. Furthermore, the results highlight that perceptual
      comparison and decision processes are flexible and can vary depending on the
      relative saliency and resources available for information processing.

PMID- 23148474
TI  - Analyzing repeated measures data on individuals nested within groups: accounting
      for dynamic group effects.
AB  - Researchers commonly collect repeated measures on individuals nested within
      groups such as students within schools, patients within treatment groups, or
      siblings within families. Often, it is most appropriate to conceptualize such
      groups as dynamic entities, potentially undergoing stochastic structural and/or
      functional changes over time. For instance, as a student progresses through
      school, more senior students matriculate while more junior students enroll,
      administrators and teachers may turn over, and curricular changes may be
      introduced. What it means to be a student within that school may thus differ from
      1 year to the next. This article demonstrates how to use multilevel linear models
      to recover time-varying group effects when analyzing repeated measures data on
      individuals nested within groups that evolve over time. Two examples are
      provided. The 1st example examines school effects on the science achievement
      trajectories of students, allowing for changes in school effects over time. The
      2nd example concerns dynamic family effects on individual trajectories of
      externalizing behavior and depression.

PMID- 23148475
TI  - How IRT can solve problems of ipsative data in forced-choice questionnaires.
AB  - In multidimensional forced-choice (MFC) questionnaires, items measuring different
      attributes are presented in blocks, and participants have to rank order the items
      within each block (fully or partially). Such comparative formats can reduce the
      impact of numerous response biases often affecting single-stimulus items (aka
      rating or Likert scales). However, if scored with traditional methodology, MFC
      instruments produce ipsative data, whereby all individuals have a common total
      test score. Ipsative scoring distorts individual profiles (it is impossible to
      achieve all high or all low scale scores), construct validity (covariances
      between scales must sum to zero), criterion-related validity (validity
      coefficients must sum to zero), and reliability estimates. We argue that these
      problems are caused by inadequate scoring of forced-choice items and advocate the
      use of item response theory (IRT) models based on an appropriate response process
      for comparative data, such as Thurstone's law of comparative judgment. We show
      that when Thurstonian IRT modeling is applied (Brown & Maydeu-Olivares, 2011),
      even existing forced-choice questionnaires with challenging features can be
      scored adequately and that the IRT-estimated scores are free from the problems of
      ipsative data.

PMID- 23148476
TI  - Bayesian methods for the analysis of small sample multilevel data with a complex
      variance structure.
AB  - Inferences from multilevel models can be complicated in small samples or complex
      data structures. When using (restricted) maximum likelihood methods to estimate
      multilevel models, standard errors and degrees of freedom often need to be
      adjusted to ensure that inferences for fixed effects are correct. These
      adjustments do not address problems in estimating variance/covariance components.
      An alternative to the adjusted likelihood method is to use Bayesian methods,
      which can produce accurate inferences about fixed effects and variance/covariance
      parameters. In this article, the authors contrast the benefits and limitations of
      likelihood and Bayesian methods in the estimation of multilevel models. The
      issues are discussed in the context of a partially clustered intervention study,
      a common intervention design that has been shown to require an adjusted
      likelihood analysis. The authors report a Monte Carlo study that compares the
      performance of an adjusted restricted maximum likelihood (REML) analysis to a
      Bayesian analysis. The results suggest that for fixed effects, the models perform
      equally well with respect to bias, efficiency, and coverage of interval
      estimates. Bayesian models with a carefully selected gamma prior for the variance
      components were more biased but also more efficient with respect to estimation of
      the variance components than the REML model. However, the results also show that
      the inferences about the variance components in partially clustered studies are
      sensitive to the prior distribution when sample sizes are small. Finally, the
      authors compare the results of a Bayesian and adjusted likelihood model using
      data from a partially clustered intervention trial.

PMID- 23148477
TI  - What influences the decision to undergo institutional delivery by skilled birth
      attendants? A cohort study in rural Andhra Pradesh, India.
AB  - INTRODUCTION: Despite continuing efforts to promote skilled institutional
      delivery, eight women die every hour in India due to causes related to pregnancy
      and child birth. The objectives of this study were to assess the prevalence and
      the determinants of institutional delivery by skilled birth attendants in a rural
      population in Andhra Pradesh, India. METHODS: This cross-sectional study used
      data from 'Young Lives', a longitudinal study on childhood poverty, and the study
      population was a cohort of 1419 rural, economically deprived women (from the
      Young Lives study) in Andhra Pradesh, India. The data are from round-1 of Young
      Lives younger cohort recruited in 2002 and followed until 2015. The participation
      rate of households was 99.5%. RESULTS: Prevalence of skilled institutional
      delivery was 36.8%. Women's education (odds ratio [OR] for secondary education
      2.06; 95% confidence interval [95%CI] 1.33-3.19), desire to be pregnant (OR 1.89;
      95% CI 1.12-3.22) and adequate prenatal care (OR 1.69; 95% CI 1.30-2.21) were
      found to be the positive determinants of skilled institutional delivery. High
      birth order (OR for second birth 0.44; 95% CI 0.32-0.60, OR for third birth 0.47;
      95% CI 0.30-0.72 and OR for >=fourth 0.47; 95% CI 0.27-0.81), schedule
      caste/schedule tribe social background (OR 0.70; 95% CI 0.53-0.93) and poor
      economic status of the household (OR for the poorest households 0.67; 95% CI 0.46
      0.99) were negatively associated with skilled institutional delivery.
      CONCLUSIONS: Despite existence of supporting schemes, the utilisation of skilled
      institutional delivery services was low in the study population. Educated women
      and women with adequate prenatal care who have a desired pregnancy were more
      likely to utilise health institutions and skilled delivery care. There is a need
      for integrated approaches through maternal health, family planning and education
      programs, and a focus on uneducated, poor women belonging to disadvantaged social
      groups.

PMID- 23148478
TI  - Multiexciton annihilation and dissociation in quantum confined semiconductor
      nanocrystals.
AB  - Recent reports of multiexciton generation (MEG), a process by which one absorbed
      photon generates multiple excitons, in lead chalcogenide nanocrystals (NCs) have
      intensified research interest in using this phenomenon to improve the efficiency
      of solar energy conversion. Practical implementation of MEG processes in solar
      cells and solar-to-fuel conversion devices requires the development of materials
      with higher MEG efficiencies and lower excitation thresholds than are currently
      available, as well as schemes for efficient multiexciton extraction before the
      ultrafast exciton-exciton annihilation occurs. This Account focuses on the
      extraction of multiexcitons by interfacial electron transfer in model NC
      molecular acceptor complexes. We provide an overview of multiexciton annihilation
      and multiexciton dissociation (MED) processes in NC-acceptor complexes of (i)
      CdSe quantum dots (QDs), (ii) CdSe/CdS quasi-type II core/shell QDs, (iii) CdSe
      quantum confined nanorods (QRs), and (iv) PbS QDs. We show that ultrafast
      electron transfer to adsorbed molecular acceptors can efficiently dissociate
      multiexcitons generated by absorption of multiple photons in (i), (ii), and
      (iii). Compared to core-only CdSe QDs, the electron hole distributions in
      CdSe/CdS quasi-type II QDs and CdSe QRs significantly improve their MED
      efficiencies by simultaneously retarding Auger recombination and facilitating
      interfacial electron transfer. Finally, in PbS-methylene blue (MB(+)) complexes,
      we show that the presence of electron acceptors does not affect the MEG
      efficiency and electron transfer to MB(+) efficiently dissociates the multiple
      excitons generated in PbS QDs. Our findings demonstrate that ultrafast
      interfacial charge transfer can be an efficient approach for extracting
      multiexcitons, and wavefunction engineering in quantum confined NCs can further
      improve MED efficiency. 

PMID- 23148479
TI  - Carbohydrate affinity for the glucose-galactose binding protein is regulated by
      allosteric domain motions.
AB  - Protein function, structure, and dynamics are intricately correlated, but studies
      on structure-activity relationships are still only rarely complemented by a
      detailed analysis of dynamics related to function (functional dynamics). Here, we
      have applied NMR to investigate the functional dynamics in two homologous
      periplasmic sugar binding proteins with bidomain composition: Escherichia coli
      glucose/galactose (GGBP) and ribose (RBP) binding proteins. In contrast to their
      structural and functional similarity, we observe a remarkable difference in
      functional dynamics: For RBP, the absence of segmental motions allows only for
      isolated structural adaptations upon carbohydrate binding in line with an induced
      fit mechanism; on the other hand, GGBP shows extensive segmental mobility in both
      apo and holo states, enabling selection of the most favorable conformation upon
      carbohydrate binding in line with a population shift mechanism. Collective
      segmental motions are controlled by the hinge composition: by swapping two
      identified key residues between RBP and GGBP we also interchange their segmental
      hinge mobility, and the doubly mutated GGBP* no longer experiences changes in
      conformational entropy upon ligand binding while the complementary RBP* shows the
      segmental dynamics observed in wild-type GGBP. Most importantly, the segmental
      interdomain dynamics always increase the apparent substrate affinity and thus,
      are functional, underscoring the allosteric control that the hinge region exerts
      on ligand binding.

PMID- 23148480
TI  - Prevalence and clinical profile of resistant hypertension among treated
      hypertensive subjects.
AB  - We assessed prevalence and clinical characteristics of resistant hypertension
      (RH) and prevalence of false RH (white-coat effect [WCE] by home blood pressure
      [BP] monitoring), among a population of 302 treated hypertensive patients, mean
      age 66.6 (+/- 13.8), 67.5% women. Resistant hypertension was defined according to
      the American Heart Association criteria. Prevalence of RH was 10%, and the
      following five variables were independently associated with it: body mass index,
      diabetes, isolated systolic hypertension, orthostatic hypotension, and use of
      beta-blockers. Prevalence of WCE among subjects with office-RH was 27.6%. Our
      study identified easily measurable parameters related to RH. Standing BP should
      be systematically measured in individuals with RH.

PMID- 23148482
TI  - Triterpenoid profile of flower and leaf cuticular waxes of heather Calluna
      vulgaris.
AB  - Analysis of the main triterpenoid profile of chloroform-soluble cuticular waxes
      of heather flowers and leaves by GC-MS revealed the following composition: five
      triterpene acids - betulinic, oleanolic, ursolic, 3-oxo-olean-12-en-28-oic and 3
      oxo-ursan-12-en-28-oic; eight monohydroxyalcohols - alpha-amyrin, beta-amyrin,
      cycloartanol, 24-methylenecycloartanol, friedelinol, germanicol, lupeol and
      taraxasterol; three dihydroxyalcohols - betulin, erythrodiol and uvaol; two
      aldehydes - oleanolic and ursolic; four ketones - alpha-amyrenone, 4-epi
      friedelin, friedelin and taraxerone and seven steroids - campesterol,
      cholesterol, sitostanol, sitosterol, stigmasterol, stigmasta-3,5-dien-7-one and
      stigmastane-3,6-dione. Triterpenoids accounted for 20% and 65% by mass of flower
      and leaf waxes, respectively, which suggest that heather leaves represent a very
      promising source of these compounds. Ursolic acid was the principal triterpenoid
      in the cuticular wax of both organs, whereas among the neutral triterpenes,
      friedelin and uvaol were the most abundant in flowers and leaves, respectively.
      This report provides the first thorough overview of the triterpenoid composition
      of cuticular waxes of heather.

PMID- 23148481
TI  - Linear quantification of lymphoid infiltration of the tumor margin: a
      reproducible method, developed with colorectal cancer tissues, for assessing a
      highly variable prognostic factor.
AB  - BACKGROUND: Lymphoid infiltration is a prognostic marker in solid tumors, such as
      colorectal, breast and lung carcinomas. However, lymphoid infiltration is
      heterogeneous and the reproducibility of quantification based on single counts
      within a tumor is very low. We aimed to develop a reproducible method for
      evaluating lymphoid infiltration in tumors. METHODS: Virtual slides were obtained
      from tissue sections from the localized colorectal carcinomas of 117 patients,
      stained for CD3 and CD45R0. We assessed the variation of lymphoid cell density by
      automatic counts in 1 mm-wide, 5 MUm-long segments of the invasive front, along
      an axis 4 mm in length running perpendicular to the invasive front of the tumor.
      RESULTS: We plotted curves of the variation of lymphocyte density across the
      tumor front. Three distinct patterns emerged from this linear quantification of
      lymphocyte (LQLI). In pattern 1, there was a high density of lymphocytes within
      the tumor. In pattern 2, lymphocyte density peaked close to the invasive margin.
      In pattern 3, lymphocytes were diffusely distributed, at low density. It was
      possible to classify all the tumors studied, and interobserver reproducibility
      was excellent (kappa =0.9). By contrast, single counts of CD3+ cells on tissue
      microarrays were highly variable for a given LQLI pattern, confirming the
      heterogeneity of lymphoid infiltration within individual tumors. In univariate
      analysis, all pathologic features (stage, metastatic lymph node ratio (LNR),
      vascular embolism, perineural invasion), CD3+ cell density, LQLI patterns for
      CD3+ and CD45R0+ cells) were found to have a significant effect on disease-free
      survival (DFS). In multivariate analysis, only the LQLI pattern for CD3+ cells
      (HR: 6.02; 95% CI: 2.74-13.18) and metastatic lymph node ratio (HR: 6.14; 95% CI:
      2.32-16.2) were associated with DFS. CONCLUSION: LQLI is an automated,
      reproducible method for the assessment of lymphoid infiltration. However,
      validation of its prognostic value in larger series is required before its
      introduction into routine practice for prognostic evaluation in patients with
      colorectal carcinomas. VIRTUAL SLIDES: The virtual slide(s) for this article can
      be found here: http://www.diagnosticpathology.diagnomx.eu/vs/9861460717895880.

PMID- 23148483
TI  - Porous alginate hydrogel functionalized with virus as three-dimensional scaffolds
      for bone differentiation.
AB  - In regenerative medicine, a synthetic extracellular matrix is crucial for
      supporting stem cells during its differentiation process to integrate into
      surrounding tissues. Hydrogels are used extensively in biomaterials as synthetic
      matrices to support the cells. However, to mimic the biological niche of a
      functional tissue, various chemical functionalities are necessary. We present
      here, a method of functionalizing a highly porous hydrogel with functional groups
      by mixing the hydrogel with a plant virus, tobacco mosaic virus (TMV), and its
      mutant. The implication of this process resides with the three important features
      of TMV: its well-defined genetic/chemical modularity, its multivalency (TMV
      capsid is composed of 2130 copies of identical subunits), and its well-defined
      structural features. Previous studies utilizing the native TMV on two-dimensional
      supports accelerated mesenchymal stem cell differentiation, and surfaces modified
      with genetically modified viral particles further enhanced cell attachment and
      differentiation. Herein we demonstrate that functionalization of a porous
      alginate scaffold can be achieved by the addition of viral particles with minimal
      processing and downstream purifications, and the cell attachment and
      differentiation within the macroporous scaffold can be effectively manipulated by
      altering the peptide or small molecule displayed on the viral particles.

PMID- 23148484
TI  - Oculus: faster sequence alignment by streaming read compression.
AB  - BACKGROUND: Despite significant advancement in alignment algorithms, the
      exponential growth of nucleotide sequencing throughput threatens to outpace
      bioinformatic analysis. Computation may become the bottleneck of genome analysis
      if growing alignment costs are not mitigated by further improvement in
      algorithms. Much gain has been gleaned from indexing and compressing alignment
      databases, but many widely used alignment tools process input reads sequentially
      and are oblivious to any underlying redundancy in the reads themselves. RESULTS:
      Here we present Oculus, a software package that attaches to standard aligners and
      exploits read redundancy by performing streaming compression, alignment, and
      decompression of input sequences. This nearly lossless process (> 99.9%) led to
      alignment speedups of up to 270% across a variety of data sets, while requiring a
      modest amount of memory. We expect that streaming read compressors such as Oculus
      could become a standard addition to existing RNA-Seq and ChIP-Seq alignment
      pipelines, and potentially other applications in the future as throughput
      increases. CONCLUSIONS: Oculus efficiently condenses redundant input reads and
      wraps existing aligners to provide nearly identical SAM output in a fraction of
      the aligner runtime. It includes a number of useful features, such as tunable
      performance and fidelity options, compatibility with FASTA or FASTQ files, and
      adherence to the SAM format. The platform-independent C++ source code is freely
      available online, at http://code.google.com/p/oculus-bio.

PMID- 23148486
TI  - Hydrogen sulfide changes adhesive properties of fibrinogen and collagen in vitro.

PMID- 23148485
TI  - Specificity of lipoprotein-associated phospholipase A(2) toward oxidized
      phosphatidylserines: liquid chromatography-electrospray ionization mass
      spectrometry characterization of products and computer modeling of interactions.
AB  - Ca(2+)-independent lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) is a
      member of the phospholipase A(2) superfamily with a distinguishing characteristic
      of high specificity for oxidatively modified sn-2 fatty acid residues in
      phospholipids that has been especially well characterized for peroxidized species
      of phosphatidylcholines (PC). The ability of Lp-PLA(2) to hydrolyze peroxidized
      species of phosphatidylserine (PS), acting as a recognition signal for clearance
      of apoptotic cells by professional phagocytes, as well as the products of the
      reaction has not been investigated. We performed liquid chromatography
      electrospray ionization mass spectrometry-based structural characterization of
      oxygenated, hydrolyzed molecular species of PS-containing linoleic acid in either
      the sn-2 position (C(18:0)/C(18:2)) or in both sn-1 and sn-2 positions
      (C(18:2)/C(18:2)), formed in the cytochrome c- and H(2)O(2)-driven enzymatic
      oxidation reaction. Cytochrome c has been chosen as a catalyst of peroxidation
      reactions because of its likely involvement in PS oxidation in apoptotic cells.
      We found that Lp-PLA(2) catalyzed the hydrolysis of both nontruncated and
      truncated (oxidatively fragmented) species of oxidized PS species, albeit with
      different efficiencies, and performed detailed characterization of the major
      reaction products: oxygenated derivatives of linoleic acid as well as
      nonoxygenated and oxygenated species of lyso-PS. Among linoleic acid products,
      derivatives oxygenated at the C(9) position, including 9-hydroxyoctadecadienoic
      acid (9-HODE), a potent ligand of G protein-coupled receptor G2A, were the most
      abundant. Computer modeling of interactions of Lp-PLA(2) with different PS
      oxidized species indicated that they are able to bind in the proximity (<5 A) of
      Ser273 and His351 of the catalytic triad. For 9-hydroxy and 9-hydroperoxy
      derivatives of oxidized PS, the sn-2 ester bond was positioned very close (<3 A)
      to the Ser273 residue, a nucleophile directly attacking the sn-2 bond, thus
      favoring the hydrolysis reaction. We suggest that oxidatively modified free fatty
      acids and lyso-PS species generated by Lp-PLA(2) may represent important signals
      facilitating and regulating the execution of apoptotic and phagocytosis programs
      essential for the control of inflammation.

PMID- 23148488
TI  - Reactive dynamics study of hypergolic bipropellants: monomethylhydrazine and
      dinitrogen tetroxide.
AB  - To gain an atomistic-level understanding on physical and chemical processes
      occurring at the interfaces of hypergolic propellants, we carried out the first
      reactive dynamic (ReaxFF) simulations to study the reactive hypergolic mixture of
      monomethylhydrazine (MMH) and dinitrogen tetroxide (NTO), in comparison with the
      ethanol (EtOH) and NTO mixture that is reactive but nonhypergolic. Our studies
      show that the MMH-NTO mixture releases energy more rapidly than the EtOH-NTO
      mixture upon mixing the fuels and oxidizers. We found that the major early
      chemical reactions between MMH and NTO are hydrogen abstractions and N-N bond
      scissions. The MMH-NTO mixture has more reaction channels than EtOH-NTO based on
      statistical analyses of chemical reaction events and channels at early stages of
      the dynamics. Analyzing the evolution of product distribution over reaction time
      shows that the oxidizer (NO(2)) diffuses into the fuels (MMH or EtOH) for the
      occurrence of reactions, demonstrating the influence of physical mixing on
      chemical reactions. Our simulations suggest that effective hypergolic systems
      require fuels with low energy barriers of H abstractions and/or bond scissions
      and oxidizers with large diffusion mobility for efficient physical mixing.

PMID- 23148487
TI  - Positive- and negative-acting regulatory elements contribute to the tissue
      specific expression of INNER NO OUTER, a YABBY-type transcription factor gene in
      Arabidopsis.
AB  - BACKGROUND: The INNER NO OUTER (INO) gene, which encodes a YABBY-type
      transcription factor, specifies and promotes the growth of the outer integument
      of the ovule in Arabidopsis. INO expression is limited to the abaxial cell layer
      of the developing outer integument of the ovule and is regulated by multiple
      regions of the INO promoter, including POS9, a positive element that when present
      in quadruplicate can produce low-level expression in the normal INO pattern.
      RESULTS: Significant redundancy in activity between different regions of the INO
      promoter is demonstrated. For specific regulatory elements, multimerization or
      the addition of the cauliflower mosaic virus 35S general enhancer was able to
      activate expression of reporter gene constructs that were otherwise incapable of
      expression on their own. A new promoter element, POS6, is defined and is shown to
      include sufficient positive regulatory information to reproduce the endogenous
      pattern of expression in ovules, but other promoter regions are necessary to
      fully suppress expression outside of ovules. The full-length INO promoter, but
      not any of the INO promoter deletions tested, is able to act as an enhancer
      blocking insulator to prevent the ectopic activation of expression by the 35S
      enhancer. Sequence conservation between the promoter regions of Arabidopsis
      thaliana, Brassica oleracea and Brassica rapa aligns closely with the functional
      definition of the POS6 and POS9 regions, and with a defined INO minimal promoter.
      The B. oleracea INO promoter is sufficient to promote a similar pattern and level
      of reporter gene expression in Arabidopsis to that observed for the Arabidopsis
      promoter. CONCLUSIONS: At least two independent regions of the INO promoter
      contain sufficient regulatory information to direct the specific pattern but not
      the level of INO gene expression. These regulatory regions act in a partially
      redundant manner to promote the expression in a specific pattern in the ovule and
      suppress expression outside of ovules. Establishment of this pattern requires
      cooperation and competition between multiple positive and negative regulatory
      elements.

PMID- 23148489
TI  - Reply to: An insight on career satisfaction level, mental distress and gender
      differences in working conditions among Japanese obstetricians and gynecologists.

PMID- 23148491
TI  - Sugar-oligoamides: synthesis of DNA minor groove binders.
AB  - Sugar-oligoamides have been designed and synthesized as structurally simple
      carbohydrate-based ligands to study carbohydrate-minor groove DNA interactions.
      Here we report an efficient solution-phase synthetic strategy to obtain two broad
      families of sugar-oligoamides. The first type, structure vector A (-Py[Me]-gamma
      Py-Ind), has a methyl group present as a substituent on the nitrogen of pyrrole
      B, connected to the C terminal of the oligoamide fragment. The second type,
      structure vector B (-Py[(CH(2))(11)OH]-gamma-Py-Ind), has an alkyl chain present
      on the nitrogen of pyrrole B connected to the C terminal of the oligoamide
      fragment and has been designed to access to di- and multivalent sugar
      oligoamides. By using sequential DIPC/HOBt coupling reactions, the oligoamide
      fragment -Py[R]-gamma-Py-Ind has been constructed. The last coupling reaction
      between the anomeric amino sugar and the oligoamide fragment was carried out by
      activating the acid derivative as a BtO- ester, which has been performed by using
      TFFH. The isolated esters (BtO-Py[R]-gamma-Py-Ind) were coupled with selected
      amino sugars using DIEA in DMF. The synthesis of two different selective model
      vectors (vector A (1) and vector B (2)) and two types of water-soluble sugar
      oligoamide ligands, with vector A structure (compounds 3-7) and with vector B
      structure (compound 8), was carried out.

PMID- 23148490
TI  - Young adult male carriers of the fragile X premutation exhibit genetically
      modulated impairments in visuospatial tasks controlled for psychomotor speed.
AB  - BACKGROUND: A previous study reported enhanced psychomotor speed, and subtle but
      significant cognitive impairments, modulated by age and by mutations in the
      fragile X mental retardation 1 (FMR1) gene in adult female fragile X premutation
      carriers (fXPCs). Because male carriers, unlike females, do not have a second,
      unaffected FMR1 allele, male fXPCs should exhibit similar, if not worse,
      impairments. Understanding male fXPCs is of particular significance because of
      their increased risk of developing fragile X-associated tremor/ataxia syndrome
      (FXTAS). METHODS: Male fXPCs (n = 18) and healthy control (HC) adults (n = 26)
      aged less than 45 years performed two psychomotor speed tasks (manual and oral)
      and two visuospatial tasks (magnitude comparison and enumeration). In the
      magnitude comparison task, participants were asked to compare and judge which of
      two bars was larger. In the enumeration task, participants were shown between one
      and eight green bars in the center of the screen, and asked to state the total
      number displayed. Enumeration typically proceeds in one of two modes: subitizing,
      a fast and accurate process that works only with a small set of items, and
      counting, which requires accurate serial-object detection and individuation
      during visual search. We examined the associations between the performance on all
      tasks and the age, full-scale intelligent quotient, and CGG repeat length of
      participants. RESULTS: We found that in the magnitude comparison and enumeration
      tasks, male fXPCs exhibited slower reaction times relative to HCs, even after
      controlling for simple reaction time. CONCLUSIONS: Our results indicate that male
      fXPCs as a group show impairments (slower reaction times) in numerical
      visuospatial tasks, which are consistent with previous findings. This adds to a
      growing body of literature characterizing the phenotype in fXPCs who are
      asymptomatic for FXTAS. Future longitudinal studies are needed to determine how
      these impairments relate to risk of developing FXTAS.

PMID- 23148493
TI  - 3D modeling of dual-gate FinFET.
AB  - The tendency to have better control of the flow of electrons in a channel of
      field-effect transistors (FETs) did lead to the design of two gates in junction
      field-effect transistors, field plates in a variety of metal semiconductor field
      effect transistors and high electron mobility transistors, and finally a gate
      wrapping around three sides of a narrow fin-shaped channel in a FinFET. With the
      enhanced control, performance trends of all FETs are still challenged by carrier
      mobility dependence on the strengths of the electrical field along the channel.
      However, in cases when the ratio of FinFET volume to its surface dramatically
      decreases, one should carefully consider the surface boundary conditions of the
      device. Moreover, the inherent non-planar nature of a FinFET demands 3D modeling
      for accurate analysis of the device performance. Using the Silvaco modeling tool
      with quantization effects, we modeled a physical FinFET described in the work of
      Hisamoto et al. (IEEE Tran. Elec. Devices 47:12, 2000) in 3D. We compared it with
      a 2D model of the same device. We demonstrated that 3D modeling produces more
      accurate results. As 3D modeling results came close to experimental measurements,
      we made the next step of the study by designing a dual-gate FinFET biased at Vg1
      >Vg2. It is shown that the dual-gate FinFET carries higher transconductance than
      the single-gate device.

PMID- 23148492
TI  - Decision tree-based learning to predict patient controlled analgesia consumption
      and readjustment.
AB  - BACKGROUND: Appropriate postoperative pain management contributes to earlier
      mobilization, shorter hospitalization, and reduced cost. The under treatment of
      pain may impede short-term recovery and have a detrimental long-term effect on
      health. This study focuses on Patient Controlled Analgesia (PCA), which is a
      delivery system for pain medication. This study proposes and demonstrates how to
      use machine learning and data mining techniques to predict analgesic requirements
      and PCA readjustment. METHODS: The sample in this study included 1099 patients.
      Every patient was described by 280 attributes, including the class attribute. In
      addition to commonly studied demographic and physiological factors, this study
      emphasizes attributes related to PCA. We used decision tree-based learning
      algorithms to predict analgesic consumption and PCA control readjustment based on
      the first few hours of PCA medications. We also developed a nearest neighbor
      based data cleaning method to alleviate the class-imbalance problem in PCA
      setting readjustment prediction. RESULTS: The prediction accuracies of total
      analgesic consumption (continuous dose and PCA dose) and PCA analgesic
      requirement (PCA dose only) by an ensemble of decision trees were 80.9% and
      73.1%, respectively. Decision tree-based learning outperformed Artificial Neural
      Network, Support Vector Machine, Random Forest, Rotation Forest, and Naive
      Bayesian classifiers in analgesic consumption prediction. The proposed data
      cleaning method improved the performance of every learning method in this study
      of PCA setting readjustment prediction. Comparative analysis identified the
      informative attributes from the data mining models and compared them with the
      correlates of analgesic requirement reported in previous works. CONCLUSION: This
      study presents a real-world application of data mining to anesthesiology. Unlike
      previous research, this study considers a wider variety of predictive factors,
      including PCA demands over time. We analyzed PCA patient data and conducted
      several experiments to evaluate the potential of applying machine-learning
      algorithms to assist anesthesiologists in PCA administration. Results demonstrate
      the feasibility of the proposed ensemble approach to postoperative pain
      management.

PMID- 23148494
TI  - Asymmetric iodolactonization utilizing chiral squaramides.
AB  - Asymmetric iodolactonization of gamma- and delta-unsaturated carboxylic acids has
      been explored in the presence of six different chiral organocatalysts 5-8. The
      catalyst 6b was found to facilitate the cyclization of 5-arylhex-5-enoic acids 1
      to the corresponding iodolactones 2 with up to 96% ee. By this protocol,
      unsaturated carboxylic acids are converted enantioselectively to synthetically
      useful delta-lactones in high yields using commercially available NIS.
      Apparently, both hydrogen bonding and aryl/aryl interactions are important for
      efficient stereodifferentiation.

PMID- 23148495
TI  - The influence of normal aging and Alzheimer's disease in autobiographical memory
      highly related to the self.
AB  - OBJECTIVE: Autobiographical memory (AM) comprises autobiographical episodes (AE)
      and personal semantics (PS). Self-defining memories (SDMs) represent peculiar
      memories highly relevant to personality processes and constitute crucial source
      for the self. To date, no research has compared normal and pathological age
      related changes in the AE and PS aspects of AM (including SDMs) and their link
      with the self. METHOD: Young adults, older adults, and patients with Alzheimer's
      disease (AD) were asked to retrieve 10 AEs, 10 PSs, and 10 SDMs based on
      identical cue-words and to complete a subjective self-concept scale measuring the
      degree of certainty and the valence of the self. Memory performance was evaluated
      for specificity and for emotional valence using quantitative scoring based on
      standard neuropsychological assessments. RESULTS: Compared with young adults,
      older adults and AD patients demonstrated a deficit in AE; nevertheless, the
      three groups performed equally for PS. Remarkably, older adults did not differ
      from young adults for SDMs characterized by high episodicity (SDMe), unlike AD
      patients. Concerning the self-concept scale, the valence of the self was more
      positive in healthy subjects than in AD patients, the latter showing higher
      scores for the degree of certainty. Self-concept measures were correlated with AM
      scores, especially SDMe, in young and older subjects but not in AD patients.
      CONCLUSION: The implication of these findings is discussed to portray the
      differences between normal aging and AD concerning the link between AM and the
      self.

PMID- 23148497
TI  - Metamemory in children with autism: exploring "feeling-of-knowing" in episodic
      and semantic memory.
AB  - BACKGROUND: Autism spectrum disorder (ASD) is a neurodevelopmental disorder
      primarily affecting social function and communication. Recently, there has been
      an interest in whether people with ASD also show memory deficits. Studies in ASD
      have revealed subtle impairments on tasks requiring participants to learn new
      information (episodic memory), but intact performance on general knowledge tasks
      (semantic memory). The novelty of this study was to explore metamemory (i.e.,
      awareness of memory performance) and to examine whether children with ASD suffer
      from a generalized metamemory deficit common to all forms of memory, or would
      only present deficits on episodic metamemory tasks. METHOD: To assess metamemory
      functioning we administered 2 feeling-of-knowing (FOK) tasks, 1 for episodic and
      1 for semantic materials. In these tasks, participants are asked to predict the
      likelihood of subsequently recognizing currently unrecalled information. RESULTS:
      It was found that children with autism made inaccurate FOK predictions, but only
      for episodic materials. CONCLUSION: A specific deficit in meta-cognition emerges
      for only one set of materials. We argue that this deficit can be conceived of as
      reflecting a deficit in recollection, stemming from an inability to cast the self
      in the past and retrieve information about the study episode.

PMID- 23148496
TI  - Neuropsychological performance and attention-deficit hyperactivity disorder
      subtypes and symptom dimensions.
AB  - OBJECTIVE: Characterization of clinical heterogeneity in attention-deficit
      hyperactivity disorder (ADHD) remains controversial. Neuropsychological and
      cognitive studies provide one type of validation data, but too often have
      considered only a narrow range of functional domains. METHOD: The current study
      examined ADHD subtype and presentation differences across a broad range of
      neurocognitive domains in a large clinically characterized, community-recruited
      sample of 498 youth (213 control, 107 ADHD-primarily inattentive [ADHD-PI], 137
      ADHD-combined [ADHD-C]), ages 6-17 years. Domains assessed included inhibition,
      working memory, arousal, processing speed, response variability, and temporal
      information processing. RESULTS: Youth with ADHD-C performed worse than youth
      with ADHD-PI in all domains, consistent with a severity model. Performance among
      a subgroup with a "restrictive inattentive" presentation indicated potential
      deficits in processing speed relative to other ADHD-PI youth, but no other
      effects. When all measures were included in the same model, cognitive control
      (executive functions, working memory, and memory span), arousal, and response
      variability each provided uniquely incremental statistical prediction of specific
      symptom dimensions and of subtype/presentation, but temporal information
      processing and processing speed did not. CONCLUSION: Results suggest the
      potential to consolidate multiple neurocognitive theories of ADHD, and that such
      consolidation will apply across putative clinical subtypes or presentations.

PMID- 23148498
TI  - A direct comparison of next generation sequencing enrichment methods using an
      aortopathy gene panel- clinical diagnostics perspective.
AB  - BACKGROUND: Aortopathies are a group of disorders characterized by aneurysms,
      dilation, and tortuosity of the aorta. Because of the phenotypic overlap and
      genetic heterogeneity of diseases featuring aortopathy, molecular testing is
      often required for timely and correct diagnosis of affected individuals. In this
      setting next generation sequencing (NGS) offers several advantages over
      traditional molecular techniques. METHODS: The purpose of our study was to
      compare NGS enrichment methods for a clinical assay targeting the nine genes
      known to be associated with aortopathy. RainDance emulsion PCR and SureSelect RNA
      bait hybridization capture enrichment methods were directly compared by enriching
      DNA from eight samples. Enriched samples were barcoded, pooled, and sequenced on
      the Illumina HiSeq2000 platform. Depth of coverage, consistency of coverage
      across samples, and the overlap of variants identified were assessed. This data
      was also compared to whole-exome sequencing data from ten individuals. RESULTS:
      Read depth was greater and less variable among samples that had been enriched
      using the RNA-bait hybridization capture enrichment method. In addition, samples
      enriched by hybridization capture had fewer exons with mean coverage less than
      10, reducing the need for followup Sanger sequencing. Variants sets produced were
      77% concordant, with both techniques yielding similar numbers of discordant
      variants. CONCLUSIONS: When comparing the design flexibility, performance, and
      cost of the targeted enrichment methods to whole-exome sequencing, the RNA-bait
      hybridization capture enrichment gene panel offers the better solution for
      interrogating the aortopathy genes in a clinical laboratory setting.

PMID- 23148499
TI  - Incidence and survival in non-hereditary amyloidosis in Sweden.
AB  - BACKGROUND: Amyloidosis is a heterogeneous disease caused by deposition of
      amyloid fibrils in organs and thereby interfering with physiological functions.
      Hardly any incidence data are available and most survival data are limited to
      specialist clinics. METHODS: Amyloidosis patients were identified from the
      Swedish Hospital Discharge and Outpatients Registers from years 2001 through
      2008. RESULTS: The incidence of non-hereditary amyloidosis in 949 patients was
      8.29 per million person-years and the diagnostic age with the highest incidence
      was over 65 years. Secondary systemic amyloidosis showed an incidence of 1 per
      million and a female excess and the largest number of subsequent rheumatoid
      arthritis deaths; the median survival was 4 years. However, as rheumatoid
      arthritis deaths also occurred in other diagnostic subtypes, the incidence of
      secondary systemic amyloidosis was likely to be about 2.0 per million. The median
      survival of patients with organ-limited amyloidosis was 6 years. Most myeloma
      deaths occurred in patients diagnosed with unspecified or 'other' amyloidosis.
      These subtypes probably accounted for most of immunoglobulin light chain (AL)
      amyloidosis cases; the median survival time was 3 years. CONCLUSIONS: The present
      diagnostic categorization cannot single out AL amyloidosis in the Swedish
      discharge data but, by extrapolation from myeloma cases, an incidence of 3.2 per
      million could be ascribed to AL amyloidosis. Similarly, based on rheumatoid
      arthritis death rates, an incidence of 2.0 could be ascribed to secondary
      systemic amyloidosis.

PMID- 23148500
TI  - The comparative effects of valsartan and amlodipine on vascular microinflammation
      in newly diagnosed hypertensive patients.
AB  - Pentraxin 3 (PTX3) is a new candidate immunoinflammatory marker that has been
      reported to be associated with cardiometabolic risk factors. We aimed to
      investigate the effects of valsartan and amlodipine on the PTX3 and C-reactive
      protein (CRP) levels in patients with essential hypertension. Patients with a
      newly diagnosed essential hypertension were admitted to our internal medicine
      outpatient clinic. Patients were randomized to one of the following intervention
      protocols: calcium channel blocker (amlodipine, 5-10 mg/day) as group A (n = 22;
      mean age +/- standard deviation [SD]: 52 +/- 11 year) and angiotensine II
      receptor blocker (valsartan, 80-320 mg/day) as group B (n = 28; mean age +/- SD:
      50 +/- 14 year). Endothelial dysfunction and systemic inflammation were evaluated
      with PTX3 and CRP. There was a significant decrease in the level of PTX3 after
      treatment in two groups (P < .05). Although there was a significant decrease in
      the level of CRP after treatment in amlodipine group, there was no significant
      decrease in the levels of PTX3 and CRP after treatment in two groups. There were
      no significant differences in the systolic and diastolic blood pressure reduction
      between the two treatment groups. In the treatment of hypertension, prior
      knowledge of the level of plasma PTX3 could be important in antihypertensive drug
      choice. C-reactive protein and PTX3 are the markers that have role in vascular
      inflammation and are found associated with the prognosis of cardiovascular
      outcomes in many trials. In our study, PTX and CRP levels were decreased when
      compared to baseline levels.

PMID- 23148502
TI  - Health risk behaviors in insured and uninsured community health center patients
      in the rural US South.
AB  - INTRODUCTION: The impact of health behaviors on the leading causes of death
      across the USA has been well demonstrated. However, limited focus has been placed
      on the leading health risk behaviors of rural Federally-Qualified Health Center
      (FQHC) patients, a particularly underserved group. The current study was
      undertaken to examine the most common risk-taking behaviors of rural FQHC
      patients and to examine if risk-taking behaviors vary between insured and
      uninsured patients. METHODS: A convenience sample of 199 patients was recruited
      at an FQHC in the rural US South. Participants completed a battery of demographic
      and health risk behavior assessments. RESULTS: The most common risk behaviors
      were eating fried foods, not eating five servings of vegetables per day, not
      eating three servings of fruit per day, drinking caloric beverages, not
      exercising regularly, not wearing a seatbelt, having sex without a condom and
      smoking. Uninsured patients were more likely to talk on their cell phones while
      driving (p<0.001), more likely to text while driving (p=0.007), more likely to
      have unprotected sex (p=0.004), more likely to drink alcohol (p=0.043) and more
      likely to not seek medical care when needed (p=0.005). CONCLUSIONS: Rural FQHC
      patients demonstrated high levels of behavioral and health risk-taking, including
      dietary-, exercise- and traffic-related risks, in a context where traditional
      prevention methods have failed to penetrate. Differences exist between insured
      and uninsured patients, indicating that the reasons behind behavioral risk-taking
      may be context-specific and need to be explored further to help identify
      intervention targets that are culturally and situationally appropriate for
      diverse rural groups.

PMID- 23148501
TI  - Redox-active magnetic resonance imaging contrast agents: studies with thiol
      bearing 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetracetic acid derivatives.
AB  - The synthesis and structure-activity relationships of a homologous series of
      1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid gadolinium(III)
      complexes bearing thiol-terminated alkyl side chains from three to nine carbons
      in length are reported. The observed binding with human serum albumin (HSA) of
      the compounds having C-3 through C-7 side chain lengths was inhibited by
      homocysteine in a manner consistent with single-site binding. The observed
      binding with HSA of the compounds having C-8 and C-9 side chain lengths was only
      partly inhibited by homocysteine, consistent with multisite binding. The binding
      affinity of the C-7 compound could be related to the HSA oxidation state. 2D 1H
      1H NMR TOCSY provided evidence of covalent binding of the europium analog of the
      C-6 compound to HSA-Cys34. The longitudinal water-proton MRI relaxivities of the
      gadolinium complexes at 7 T increased upon binding to HSA. On the basis of these
      results, the C-6 and C-7 compounds were identified as promising redox-sensitive
      MRI contrast agents.

PMID- 23148503
TI  - Selective soil particle adherence to hands: implications for understanding oral
      exposure to soil contaminants.
AB  - Over the last 30 years, there has been extensive research designed to quantify
      the extent of oral bioavailability and bioaccessibility of organic and inorganic
      contaminants in soil. One aspect of this research is the soil particle size
      selected to represent environmental exposures, which may affect study results and
      comparability across studies. Different research groups have studied soil
      particle sizes ranging from <45 MUm to <2000 MUm. This article reviews the
      historical and technical considerations that pertain to the selection of an
      appropriate particle size fraction for evaluating the relative oral
      bioavailability of chemicals from soil, which include (1) how the resultant data
      will be used in human health risk assessment, (2) soil fractions historically
      used in oral bioavailability studies, (3) studies of soil adherence to human
      hands, (4) the distribution of contaminants in soils as a function of particle
      size, and (5) the effect of differential bioavailability as a function of soil
      particle size and geochemical matrix. These factors are first discussed from a
      general perspective, applicable to all contaminants in soil, and then more
      specifically for polycyclic aromatic hydrocarbons (PAHs) in soil. Based on this
      review, a specific soil particle size of <150 MUm is recommended for future
      studies on the oral bioavailability and bioaccessibility of PAHs in soil.

PMID- 23148504
TI  - People, plants and health: a conceptual framework for assessing changes in
      medicinal plant consumption.
AB  - BACKGROUND: A large number of people in both developing and developed countries
      rely on medicinal plant products to maintain their health or treat illnesses.
      Available evidence suggests that medicinal plant consumption will remain stable
      or increase in the short to medium term. Knowledge on what factors determine
      medicinal plant consumption is, however, scattered across many disciplines,
      impeding, for example, systematic consideration of plant-based traditional
      medicine in national health care systems. The aim of the paper is to develop a
      conceptual framework for understanding medicinal plant consumption dynamics.
      Consumption is employed in the economic sense: use of medicinal plants by
      consumers or in the production of other goods. METHODS: PubMed and Web of
      Knowledge (formerly Web of Science) were searched using a set of medicinal plant
      key terms
      (folk/peasant/rural/traditional/ethno/indigenous/CAM/herbal/botanical/phytotherap
      ); each search terms was combined with terms related to medicinal plant
      consumption dynamics (medicinal plants/health care/preference/trade/treatment
      seeking
      behavior/domestication/sustainability/conservation/urban/migration/climate
      change/policy/production systems). To eliminate studies not directly focused on
      medicinal plant consumption, searches were limited by a number of terms
      (chemistry/clinical/in
      vitro/antibacterial/dose/molecular/trial/efficacy/antimicrobial/alkaloid/bioactiv
      /inhibit/antibody/purification/antioxidant/DNA/rat/aqueous). A total of 1940
      references were identified; manual screening for relevance reduced this to 645
      relevant documents. As the conceptual framework emerged inductively, additional
      targeted literature searches were undertaken on specific factors and link,
      bringing the final number of references to 737. RESULTS: The paper first defines
      the four main groups of medicinal plant users (1. Hunter-gatherers, 2. Farmers
      and pastoralists, 3. Urban and peri-urban people, 4. Entrepreneurs) and the three
      main types of benefits (consumer, producer, society-wide) derived from medicinal
      plants usage. Then a single unified conceptual framework for understanding the
      factors influencing medicinal plant consumption in the economic sense is
      proposed; the framework distinguishes four spatial levels of analysis
      (international, national, local, household) and identifies and describes 15
      factors and their relationships. CONCLUSIONS: The framework provides a basis for
      increasing our conceptual understanding of medicinal plant consumption dynamics,
      allows a positioning of existing studies, and can serve to guide future research
      in the area. This would inform the formation of future health and natural
      resource management policies.

PMID- 23148505
TI  - Annexin A2 modulates radiation-sensitive transcriptional programming and cell
      fate.
AB  - We previously established annexin A2 as a radioresponsive protein associated with
      anchorage independent growth in murine epidermal cells. In this study, we
      demonstrate annexin A2 nuclear translocation in human skin organotypic culture
      and murine epidermal cells after exposure to X radiation (10-200 cGy), supporting
      a conserved nuclear function for annexin A2. Whole genome expression profiling in
      the presence and absence of annexin A2 [shRNA] identified fundamentally altered
      transcriptional programming that changes the radioresponsive transcriptome.
      Bioinformatics predicted that silencing AnxA2 may enhance cell death responses to
      stress in association with reduced activation of pro-survival signals such as
      nuclear factor kappa B. This prediction was validated by demonstrating a
      significant increase in sensitivity toward tumor necrosis factor alpha-induced
      cell death in annexin A2 silenced cells, relative to vector controls, associated
      with reduced nuclear translocation of RelA (p65) following tumor necrosis factor
      alpha treatment. These observations implicate an annexin A2 niche in cell fate
      regulation such that AnxA2 protects cells from radiation-induced apoptosis to
      maintain cellular homeostasis at low-dose radiation.

PMID- 23148506
TI  - The photon-isoeffective dose in boron neutron capture therapy.
AB  - With the aim to relate the effects observed in a clinical boron neutron capture
      therapy protocol to the corresponding outcomes in a standard photon radiation
      therapy, "RBE-weighted" doses are customarily calculated by adding the
      contributions of the different radiations, each one weighted by a fixed (dose and
      dose rate independent) relative biological effectiveness factor. In this study,
      the use of fixed factors is shown to have a formal inconsistency, which in
      practice leads to unrealistically high tumor doses. We then introduce a more
      realistic approach that essentially exploits all the experimental information
      available from survival experiments. The proposed formalism also includes first
      order repair of sublethal lesions by means of the generalized Lea-Catcheside
      factor in the modified linear-quadratic model, and considers synergistic
      interactions between different radiations. This formalism is of sufficient
      simplicity therefore to be directly included in all BNCT treatment planning
      systems. In light of this formalism, the photon-isoeffective doses for two BNCT
      clinical targets were computed and compared with the standard dose calculation
      procedure. For the case of brain tumors and clinically relevant absorbed doses,
      the proposed approach derives isoeffective doses that are much lower than the
      fixed RBE method, regardless of considering synergism. Thus, for a tumor that
      receives a mean total absorbed dose of 15 Gy (value achievable with 50 ppm of
      boron concentration and typical beams used in the clinic), the photon
      isoeffective doses are 28 Gy (IsoE) and 30 Gy (IsoE) (without and with synergism,
      respectively), in contrast to 51 Gy (RBE) for the fixed RBE method. When the
      clinical outcome of the Argentine cutaneous melanoma treatments is assessed with
      regard to the doses derived from the standard procedure, it follows that the
      fixed RBE approach is not suitable to understand the observed clinical results in
      terms of the photon radiotherapy data. Moreover, even though the assumed (10)B
      concentration in tumors is lowered to reduce the obtained doses with the standard
      procedure, the fixed RBE approach is still unsuitable to explain the observed
      outcomes (the model is always rejected with P values of virtually zero).
      Additionally, the numbers of controlled tumors predicted by the proposed approach
      are statistically consistent with observed outcomes. As a by-product of this
      work, a dose-response clinical reference for single-fraction melanoma treatments
      is developed.

PMID- 23148507
TI  - The association between chronic kidney disease and cardiovascular disease risk
      factors in atomic bomb survivors.
AB  - Atomic bomb (A-bomb) radiation is associated with cardiovascular disease (CVD)
      and metabolic CVD risk factors. Chronic kidney disease (CKD) is also known to be
      a risk factor for CVD and little is known whether CKD is associated with A-bomb
      radiation. To examine whether CKD is associated with CVD risk factors or with A
      bomb radiation in A-bomb survivors, we classified renal dysfunction in 1,040 A
      bomb survivors who were examined in 2004-2007 as normal [n = 121; estimated
      glomerular filtration rate (eGFR) >= 90 ml/min/1.73 m(2)]; mild (n = 686; eGFR 60
      89 ml/min/1.73 m(2)); moderate (n = 217; eGFR 30-59 ml/min/1.73 m(2)); or severe
      (n = 16; eGFR <30 ml/min/1.73 m(2)). Also, we diagnosed subjects in the moderate
      and severe renal dysfunction groups as having CKD (n = 233; eGFR <59 ml/min/1.73
      m(2)). After adjusting for age, gender, and smoking and drinking habits, we
      looked for an association between renal dysfunction and hypertension, diabetes
      mellitus (DM), hyperlipidemia, and metabolic syndrome (MetS), and between renal
      dysfunction and A-bomb radiation. Hypertension [odds ratio (OR), 1.57; 95%
      confidence interval (CI), 1.12-2.20, P = 0.009]; DM (OR, 1.79; 95% CI, 1.23-2.61,
      P = 0.002); hyperlipidemia (OR, 1.55; 95% CI, 1.12-2.14, P = 0.008); and MetS
      (OR, 1.86; 95% CI, 1.32-2.63, P < 0.001) were associated with CKD
      (moderate/severe renal dysfunction), and hyperlipidemia and MetS were also
      associated with mild renal dysfunction. CKD (OR/Gy, 1.29; 95% CI, 1.01-1.63, P =
      0.038) and severe renal dysfunction (OR/Gy, 3.19; 95% CI, 1.63-6.25, P < 0.001)
      were significantly associated with radiation dose. CKD associated with radiation
      may have played a role in the development of CVD among A-bomb survivors.

PMID- 23148508
TI  - Variations in the RBE for cell killing along the depth-dose profile of a
      modulated proton therapy beam.
AB  - Considerable evidence now exists to show that that the relative biological
      effectiveness (RBE) changes considerably along the proton depth-dose
      distribution, with progressively higher RBE values at the distal part of the
      modulated, or spread out Bragg peak (SOBP) and in the distal dose fall-off (DDF).
      However, the highly variable nature of the existing studies (with regards to cell
      lines, and to the physical properties and dosimetry of the various proton beams)
      precludes any consensus regarding the RBE weighting factor at any position in the
      depth-dose profile. We have thus conducted a systematic study on the variation in
      RBE for cell killing for two clinical modulated proton beams at Indiana
      University and have determined the relationship between the RBE and the dose
      averaged linear energy transfer (LETd) of the protons at various positions along
      the depth-dose profiles. Clonogenic assays were performed on human Hep2 laryngeal
      cancer cells and V79 cells at various positions along the SOBPs of beams with
      incident energies of 87 and 200 MeV. There was a marked variation in the
      radiosensitivity of both cell lines along the SOBP depth-dose profile of the 87
      MeV proton beam. Using Hep2 cells, the D(0.1) isoeffect dose RBE values
      (normalized against (60)Co) were 1.46 at the middle of SOBP, 2.1 at the distal
      end of the SOBP and 2.3 in the DDF. For V79 cells, the D(0.1) isoeffect RBE for
      the 87 MEV beam were 1.23 for the proximal end of the SOBP: 1.46 for the distal
      SOBP and 1.78 for the DDF. Similar D(0.1) isoeffect RBE values were found for
      Hep2 cells irradiated at various positions along the depth-dose profile of the
      200 MeV beam. Our experimentally derived RBE values were significantly correlated
      (P = 0.001) with the mean LETd of the protons at the various depths, which
      confirmed that proton RBE is highly dependent on LETd. These in vitro data
      suggest that the RBE of the proton beam at certain depths is greater than 1.1, a
      value currently used in most treatment planning algorithms. Thus, the potential
      for increased cell killing and normal tissue damage in the distal regions of the
      proton SOBP may be greater than originally thought.

PMID- 23148509
TI  - DNA damage enhancement from gold nanoparticles for clinical MV photon beams.
AB  - In this study, we quantify the relative damage enhancement due to the presence of
      gold nanoparticles (GNP) in vitro in a clinical 6 MV beam for various delivery
      parameters and depths. It is expected that depths and delivery modes that produce
      a larger proportions of low-energy photons will have a larger effect on the cell
      samples containing GNP. HeLa cells with and without 50 nm GNP were irradiated at
      depths of 1.5, 5, 10, 15 and 20 cm. Conventional beams with square aperture sizes
      5, 10 and 15 cm at isocenter, and flattening filter free (FFF) beams were used.
      Relative DNA damage enhancement with GNP was evaluated by gamma-H2AX staining.
      Statistically significant increases in DNA damage with GNP, compared to the
      absence of GNP, were observed for all depths and delivery modes. Relative to the
      shallowest depth, damage enhancement was observed to increase as a function of
      increasing depth for all deliveries. For the conventional (open field) delivery,
      DNA damage enhancement with GNP was seen to increase as a function of field size.
      For FFF delivery, a substantial increase in enhancement was found relative to the
      conventional field delivery. The measured relative DNA damage enhancement
      validates the theoretically predicted trends as a function of depth and delivery
      mode for clinical MV photon beams. The results of this study open new
      possibilities for the clinical development of gold nanoparticle-aided radiation
      therapy.

PMID- 23148510
TI  - Proline catalyzed alpha-aminoxylation reaction in the synthesis of biologically
      active compounds.
AB  - The search for new and efficient ways to synthesize optically pure compounds is
      an active area of research in organic synthesis. Asymmetric catalysis provides a
      practical, cost-effective, and efficient method to create a variety of complex
      natural products containing multiple stereocenters. In recent years, chemists
      have become more interested in using small organic molecules to catalyze organic
      reactions. As a result, organocatalysis has emerged both as a promising strategy
      and as an alternative to catalysis with expensive proteins or toxic metals.  One
      of the most successful and widely studied secondary amine-based organocatalysts
      is proline. This small molecule can catalyze numerous reactions such as the
      aldol, Mannich, Michael addition, Robinson annulation, Diels-Alder, alpha
      functionalization, alpha-amination, and alpha-aminoxylation reactions. Catalytic
      and enantioselective alpha-oxygenation of carbonyl compounds is an important
      reaction to access a variety of useful building blocks for bioactive molecules.
      Proline catalyzed alpha-aminoxylation using nitrosobenzene as oxygen source,
      followed by in situ reduction, gives enantiomerically pure 1,2-diol. This
      molecule can then undergo a variety of organic reactions. In addition, proline
      organocatalysis provides access to an assortment of biologically active natural
      products including mevinoline (a cholesterol lowering drug), tetrahydrolipstatin
      (an antiobesity drug), R(+)-alpha-lipoic acid, and bovidic acid.  In this
      Account, we present an iterative organocatalytic approach to synthesize both syn-
      and anti-1,3-polyols, both enantio- and stereoselectively. This method is
      primarily based on proline-catalyzed sequential alpha-aminoxylation and Horner
      Wadsworth-Emmons (HWE) olefination of aldehyde to give a gamma-hydroxy ester. In
      addition, we briefly illustrate the broad application of our recently developed
      strategy for 1,3-polyols, which serve as valuable, enantiopure building blocks
      for polyketides and other structurally diverse and complex natural products.
      Other research groups have also applied similar strategies to prepare such
      bioactive molecules as littoralisone, brasoside and (+)-cytotrienin A. Among the
      various synthetic approaches reported for 1,3-polyols, our organocatalytic
      iterative approach appears to be very promising and robust. This method combines
      the merit of organocatalytic reaction with an easy access to both
      enantiomerically pure forms of proline, mild reaction conditions, and tolerance
      to both air and moisture. In this Account, we present the latest applications of
      organocatalysis and how organic chemists can use this new tool for the total
      synthesis of complex natural products.

PMID- 23148511
TI  - Characterization of the second ion-binding site in the G domain of H-Ras.
AB  - Ras is a small monomeric GTPase acting as molecular switch in multiple cellular
      processes. The N-terminal G domain of Ras binds GTP or GDP accompanied by a
      magnesium ion, which is strictly required for GTPase activity and performs a
      structural role. Another ion-binding site on the opposite face of the G domain
      has been recently observed to specifically associate with calcium acetate in the
      crystal [Buhrman, G., et al. (2010) Proc. Natl. Aacd. Sci. U.S.A. 107, 4931
      4936]. In this article, we report thermodynamic measurements of the affinity and
      specificity of the remote ion-binding site in H-Ras as observed in solution.
      Using (15)N-(1)H nuclear magnetic resonance spectroscopy, we determined that, in
      contrast to the crystalline state, the remote site in solution is specific for a
      divalent cation, binding both calcium and magnesium with anions playing a minimal
      role. The affinity of the remote site for divalent cations is in the low
      millimolar range and remarkably different for GDP- and GppNHp-bound forms of the
      G domain, indicating that the GTP-binding pocket and the remote site are
      allosterically coupled through the distance of more than 25 A. Considering that
      the remote site is oriented toward the membrane surface in vivo, we hypothesize
      that its cognate biological ligand might be a positively charged group extending
      from a lipid or an integral membrane protein.

PMID- 23148512
TI  - Two new compounds from Potentilla multicaulis Bunge.
AB  - Two new compounds (triterpenoid saponin and heterocyclic compound), 2alpha,3beta,
      19alpha,23,30-pentahydroxyurs-12-en-28-oic acid-28-O-beta-d-glucopyranosyl ester
      (1) and N-hydroxyl-hexahydroazepin-2,4-diones (2), with 11 known compounds,
      picein (3), (7S,8R)-dihydrodehydrodiconiferyl alcohol-9'-O-beta-d-glucopyranoside
      (4), (+)-1-hydroxy-2-epipinoresinol-1-beta-d-glucoside (5), (+)-1
      hydroxypinoresinol-1-beta-d-glucoside (6), (+)-1-hydroxypinoresinol-4'-beta-d
      glucoside (7), schaftside (6-C-beta-d-glucopyranosyl-8-C-alpha-l-arabinosyl
      apigenin) (8), isoschaftside (6-C-alpha-l-arabinosyl-8-C-beta-d-glucopyranosyl
      apigenin) (9), isorhamnetin-3-O-beta-d-glucopyranoside (10), quercetin-3-O-beta
      glucuronide (11), 8-O-methylherbacetin-3-O-sophoroside (12) and kaempferol (13),
      were isolated from Potentilla multicaulis Bunge. The structure of the compounds
      was elucidated by chemical and spectral evidence.

PMID- 23148513
TI  - Vaccinelike and prophylactic treatments of EAE with novel I-domain antigen
      conjugates (IDAC): targeting multiple antigenic peptides to APC.
AB  - The objective of this work is to utilize novel I-domain antigenic-peptide
      conjugates (IDAC) for targeting antigenic peptides to antigen-presenting cells
      (APC) to simulate tolerance in experimental autoimmune encephalomyelitis (EAE).
      IDAC-1 and IDAC-3 molecules are conjugates between the I-domain protein and PLP
      Cys and Ac-PLP-Cys-NH(2) peptides, respectively, tethered to N-terminus and Lys
      residues on the I-domain. The hypothesis is that the I-domain protein binds to
      ICAM-1 and PLP peptide binds to MHC-II on the surface of APC; this binding event
      inhibits the formation of the immunological synapse at the APC-T-cell interface
      to alter T-cell differentiation from inflammatory to regulatory phenotypes.
      Conjugation of peptides to the I-domain did not change the secondary structure of
      IDAC molecules as determined by circular dichroism spectroscopy. The efficacies
      of IDAC-1 and -3 were evaluated in EAE mice by administering iv or sc injections
      of IDAC in a prophylactic or a vaccinelike dosing schedule. IDAC-3 was better
      than IDAC-1 in suppressing and delaying the onset of EAE when delivered in
      prophylactic and vaccinelike manners. IDAC-3 also suppressed subsequent relapse
      of the disease. The production of IL-17 was lowered in the IDAC-3-treated mice
      compared to those treated with PBS. In contrast, the production of IL-10 was
      increased, suggesting that there is a shift from inflammatory to regulatory T
      cell populations in IDAC-3-treated mice. In conclusion, the I-domain can
      effectively deliver antigenic peptides in a vaccinelike or prophylactic manner
      for inducing immunotolerance in the EAE mouse model.

PMID- 23148514
TI  - Postoperative recovery and its association with health-related quality of life
      among day surgery patients.
AB  - BACKGROUND: Day surgery holds advantages for both the patient and the health
      care organization. However, recovery beyond the first postoperative week and
      following different types of surgery has not been explored to any greater degree.
      The current aims were to prospectively describe postoperative recovery and health
      related quality of life among different groups of day surgery patients and to
      explore the association between postoperative recovery and health-related quality
      of life 30 days after discharge. METHODS: A consecutive sample of 607 adult day
      surgery patients undergoing orthopaedic, gynaecological or general surgery was
      included. Postoperative recovery was assessed on days 1, 7 and 14 using the
      Swedish Post-discharge Surgery Recovery scale and the Quality of Recovery-23
      scale. The EQ-5D was used to assess health-related quality of life preoperatively
      and 30 days following discharge. A repeated measure ANOVA was conducted to
      evaluate postoperative recovery from day 1 to day 14 and between different
      surgical groups. Hierarchical multiple linear regression models were used to
      explore the association between postoperative recovery and health-related quality
      of life. RESULTS: Postoperative recovery improved from day 1 to 14 in all
      surgical groups (p<0.001). The orthopaedic patients had lower postoperative
      recovery on day 14 compared to the general and the gynaecological patients
      (p<0.001). Health-related quality of life was lower among orthopaedic patients
      (p<0.001), even if significant improvements over time were seen in all groups.
      Recovery on day 7 was associated with health-related quality of life 30 days
      after the day surgery (p<0.05). CONCLUSION: Particularly orthopaedic day surgical
      patients seem to favour a closer follow-up in order to support recovery and
      thereby also positively influence health-related quality of life.

PMID- 23148515
TI  - An easily accessible donor-pi-acceptor-conjugated small molecule from a 4,8
      dialkoxybenzo[1,2-b:4,5-b']dithiophene unit for efficient solution-processed
      organic solar cells.
AB  - A new donor-acceptor-conjugated organic small molecule, BDT(TBT)(2), comprised of
      benzo[1,2-b:4,5-b']dithiophene and 2,1,3-benzothiadiazole units was designed and
      synthesized. The small molecule BDT(TBT)(2) in its thin film showed an absorption
      band in the range of 300-700 nm with an absorption edge at 650 nm and an optical
      band gap of 1.90 eV. As estimated from the cyclic voltammetry measurements, the
      HOMO and LUMO energy levels of BDT(TBT)(2) were -5.44 and -3.37 eV, respectively.
      The spin-coated thin film of BDT(TBT)(2) exhibited p-channel output
      characteristics with a hole mobility of 2.7 * 10(-6). BDT(TBT)(2), when explored
      as an electron-donor material in solution-processed bulk-heterojunction organic
      solar cells in conjunction with a PC(71)BM acceptor with an active layer
      thickness of 50-55 nm, generated a power conversion efficiency (PCE) of 1.18%. A
      more impressive PCE of ~2.9% with a short-circuit current density (J(sc)) of 7.94
      mA cm(-2) and an open-circuit voltage (V(oc)) of 0.89 V was achieved when the
      active layer of the cell was annealed at higher temperature (~180  degrees C).

PMID- 23148517
TI  - Improving accuracy for cancer classification with a new algorithm for genes
      selection.
AB  - BACKGROUND: Even though the classification of cancer tissue samples based on gene
      expression data has advanced considerably in recent years, it faces great
      challenges to improve accuracy. One of the challenges is to establish an
      effective method that can select a parsimonious set of relevant genes. So far,
      most methods for gene selection in literature focus on screening individual or
      pairs of genes without considering the possible interactions among genes. Here we
      introduce a new computational method named the Binary Matrix Shuffling Filter
      (BMSF). It not only overcomes the difficulty associated with the search schemes
      of traditional wrapper methods and overfitting problem in large dimensional
      search space but also takes potential gene interactions into account during gene
      selection. This method, coupled with Support Vector Machine (SVM) for
      implementation, often selects very small number of genes for easy model
      interpretability. RESULTS: We applied our method to 9 two-class gene expression
      datasets involving human cancers. During the gene selection process, the set of
      genes to be kept in the model was recursively refined and repeatedly updated
      according to the effect of a given gene on the contributions of other genes in
      reference to their usefulness in cancer classification. The small number of
      informative genes selected from each dataset leads to significantly improved
      leave-one-out (LOOCV) classification accuracy across all 9 datasets for multiple
      classifiers. Our method also exhibits broad generalization in the genes selected
      since multiple commonly used classifiers achieved either equivalent or much
      higher LOOCV accuracy than those reported in literature. CONCLUSIONS: Evaluation
      of a gene's contribution to binary cancer classification is better to be
      considered after adjusting for the joint effect of a large number of other genes.
      A computationally efficient search scheme was provided to perform effective
      search in the extensive feature space that includes possible interactions of many
      genes. Performance of the algorithm applied to 9 datasets suggests that it is
      possible to improve the accuracy of cancer classification by a big margin when
      joint effects of many genes are considered.

PMID- 23148516
TI  - Costs of delivering human papillomavirus vaccination to schoolgirls in Mwanza
      Region, Tanzania.
AB  - BACKGROUND: Cervical cancer is the leading cause of female cancer-related deaths
      in Tanzania. Vaccination against human papillomavirus (HPV) offers a new
      opportunity to control this disease. This study aimed to estimate the costs of a
      school-based HPV vaccination project in three districts in Mwanza Region (NCT ID:
      NCT01173900), Tanzania and to model incremental scaled-up costs of a regional
      vaccination program. METHODS: We first conducted a top-down cost analysis of the
      vaccination project, comparing observed costs of age-based (girls born in 1998)
      and class-based (class 6) vaccine delivery in a total of 134 primary schools.
      Based on the observed project costs, we then modeled incremental costs of a
      scaled-up vaccination program for Mwanza Region from the perspective of the
      Tanzanian government, assuming that HPV vaccines would be delivered through the
      Expanded Programme on Immunization (EPI). RESULTS: Total economic project costs
      for delivering 3 doses of HPV vaccine to 4,211 girls were estimated at about
      US$349,400 (including a vaccine price of US$5 per dose). Costs per fully
      immunized girl were lower for class-based delivery than for age-based delivery.
      Incremental economic scaled-up costs for class-based vaccination of 50,290 girls
      in Mwanza Region were estimated at US$1.3 million. Economic scaled-up costs per
      fully-immunized girl were US$26.41, including HPV vaccine at US$5 per dose.
      Excluding vaccine costs, vaccine could be delivered at an incremental economic
      cost of US$3.09 per dose and US$9.76 per fully-immunized girl. Financial scaled
      up costs, excluding costs of the vaccine and salaries of existing staff were
      estimated at US$1.73 per dose. CONCLUSIONS: Project costs of class-based
      vaccination were found to be below those of age-based vaccination because of more
      eligible girls being identified and higher vaccine uptake. We estimate that
      vaccine can be delivered at costs that would make HPV vaccination a very cost
      effective intervention. Potentially, integrating HPV vaccine delivery with cost
      effective school-based health interventions and a reduction of vaccine price
      below US$5 per dose would further reduce the costs per fully HPV-immunized girl.

PMID- 23148518
TI  - Genome-scale case-control analysis of CD4+ T-cell DNA methylation in juvenile
      idiopathic arthritis reveals potential targets involved in disease.
AB  - BACKGROUND: Juvenile Idiopathic Arthritis (JIA) is a complex autoimmune
      rheumatic disease of largely unknown cause. Evidence is growing that epigenetic
      variation, particularly DNA methylation, is associated with autoimmune disease.
      However, nothing is currently known about the potential role of aberrant DNA
      methylation in JIA. As a first step to addressing this knowledge gap, we have
      profiled DNA methylation in purified CD4+ T cells from JIA subjects and controls.
      Genomic DNA was isolated from peripheral blood CD4+ T cells from 14
      oligoarticular and polyarticular JIA cases with active disease, and healthy age-
      and sex-matched controls. Genome-scale methylation analysis was carried out using
      the Illumina Infinium HumanMethylation27 BeadChip. Methylation data at >25,000
      CpGs was compared in a case-control study design. RESULTS: Methylation levels
      were significantly different (FDR adjusted p<0.1) at 145 loci. Removal of four
      samples exposed to methotrexate had a striking impact on the outcome of the
      analysis, reducing the number of differentially methylated loci to 11. The
      methotrexate-naive analysis identified reduced methylation at the gene encoding
      the pro-inflammatory cytokine IL32, which was subsequently replicated using a
      second analysis platform and a second set of case-control pairs. CONCLUSIONS: Our
      data suggests that differential T cell DNA methylation may be a feature of JIA,
      and that reduced methylation at IL32 is associated with this disease. Further
      work in larger prospective and longitudinal sample collections is required to
      confirm these findings, assess whether the identified differences are causal or
      consequential of disease, and further investigate the epigenetic modifying
      properties of therapeutic regimens.

PMID- 23148519
TI  - A case report of type VI dual left anterior descending coronary artery anomaly
      presenting with non-ST-segment elevation myocardial infarction.
AB  - BACKGROUND: Type VI dual left anterior descending artery (LAD) is a rare coronary
      anomaly, the first case of which has recently been described. This is the first
      report of type VI dual LAD anomaly in which the patient presented with non-ST
      segment elevation myocardial infarction and percutaneous coronary intervention
      was performed in the anomalously originating LAD. CASE PRESENTATION: A 52-year
      old man with diabetes, hypertension and hyperlipidemia presented with chest pain
      without ST elevation on EKG, although the patient's troponin I level was
      elevated. Coronary angiography revealed a short LAD originating from the left
      main coronary artery and a long LAD originating from the proximal portion of the
      right coronary artery (RCA). Three-dimensional reconstruction of computed
      tomography of images revealed that the long LAD originated from the proximal RCA
      and coursed between the right ventricular outflow tract (RVOT) and the aortic
      root before entering the mid anterior interventricular groove. The high take-off
      RCA originated underneath the RVOT, pointing downwards and forming an acute angle
      with the proximal portion of the long LAD. The anomalous long LAD displayed
      significant stenosis. We performed successful percutaneous coronary intervention
      (PCI) in the anomalous artery. CONCLUSION: With accurate understanding of the
      coronary anatomy and appropriate hardware selection, successful PCI can be
      performed in the in the long LAD in patients with type VI dual LAD anomaly.

PMID- 23148520
TI  - Water control over the chemoselectivity of a Ti/Ni multimetallic system: Heck- or
      reductive-type cyclization reactions of alkyl iodides.
AB  - A versatile Ti/Ni multimetallic protocol is described for the efficient catalysis
      of two different reactions, namely a Heck- and reductive-type cyclization of
      alkyl iodides, in the absence or presence of water, respectively. Noteworthy, the
      versatility of Ti(III) chemistry allows an oxidative ending step under reductive
      conditions to give Heck-type products, and the good H-atom transfer capabilities
      of Ti(III)-aqua complexes ensure reductive-type cyclizations.

PMID- 23148521
TI  - Snus user identity and addiction: a Swedish focus group study on adolescents.
AB  - BACKGROUND: The teenage years are the years when adolescents seek their identity,
      and part of this involves experimenting with tobacco. The use of tobacco as such,
      and norms among their friends, is more important to the adolescents than the
      norms of parents when it comes to using tobacco or not. The aim was to explore
      the significance of using snus for adolescents, and attitudes to snus, as well as
      the reasons why they began using snus and what maintained and facilitated the use
      of snus. METHODS: Adolescents who use snus were interviewed in focus groups. The
      material was analysed using content analysis. RESULTS: Four groups of boys and
      one group of girls were interviewed, a total of 27 students from the upper
      secondary vocational program. Three themes related to the students' opinions on
      and experiences of using snus were found: Circumstances pertaining to snus debut
      indicate what makes them start using snus. Upholding, which focuses on the
      problem of becoming addicted and development of identity, and approach, where the
      adolescents reflect on their snus habits in relation to those around them. A
      number of factors were described as relevant to behaviour and norm building for
      the development into becoming a snus user. Attitudes and actions from adults and
      friends as well as - for the boys - development of an identity as a man and a
      craftsman influenced behaviour. CONCLUSIONS: The results showed that development
      of identity was of major importance when adolescents start using snus. The
      adolescents were initially unable to interpret the early symptoms of abstinence
      problems, but subsequently became well aware of being addicted. Once they were
      stuck in addiction and in the creation of an image and identity, it was difficult
      to stop using snus. These factors are important when considering interventions of
      normative changes and tobacco prevention in schools as well as among parents.

PMID- 23148522
TI  - Design, synthesis, and antidiabetic activity of 4-phenoxynicotinamide and 4
      phenoxypyrimidine-5-carboxamide derivatives as potent and orally efficacious TGR5
      agonists.
AB  - 4-Phenoxynicotinamide and 4-phenoxypyrimidine-5-carboxamide derivatives as potent
      and orally efficacious TGR5 agonists are reported. Several 4-phenoxynicotinamide
      derivatives were found to activate human and mouse TGR5 (hTGR5 and mTGR5) with
      EC50 values in the low nanomolar range. Compound 23g, with an EC50 value of 0.72
      nM on hTGR5 and an EC50 value of 6.2 nM on mTGR5, was selected for further in
      vivo efficacy studies. This compound exhibited a significant dose-dependent
      glucagon-like peptide-1 (GLP-1) secretion effect. A single oral dose of 23g (50
      mg/kg) significantly reduced blood glucose levels in db/db mice and caused a 49%
      reduction in the area under the blood glucose curve (AUC)0-120 min following an
      oral glucose tolerance test (OGTT) in imprinting control region (ICR) mice.
      However, 23g stimulated gallbladder filling, which might result in side effects
      to the gallbladder.

PMID- 23148523
TI  - Visualising associations between paired 'omics' data sets.
AB  - BACKGROUND: Each omics platform is now able to generate a large amount of data.
      Genomics, proteomics, metabolomics, interactomics are compiled at an ever
      increasing pace and now form a core part of the fundamental systems biology
      framework. Recently, several integrative approaches have been proposed to extract
      meaningful information. However, these approaches lack of visualisation outputs
      to fully unravel the complex associations between different biological entities.
      RESULTS: The multivariate statistical approaches 'regularized Canonical
      Correlation Analysis' and 'sparse Partial Least Squares regression' were recently
      developed to integrate two types of highly dimensional 'omics' data and to select
      relevant information. Using the results of these methods, we propose to revisit
      few graphical outputs to better understand the relationships between two 'omics'
      data and to better visualise the correlation structure between the different
      biological entities. These graphical outputs include Correlation Circle plots,
      Relevance Networks and Clustered Image Maps. We demonstrate the usefulness of
      such graphical outputs on several biological data sets and further assess their
      biological relevance using gene ontology analysis. CONCLUSIONS: Such graphical
      outputs are undoubtedly useful to aid the interpretation of these promising
      integrative analysis tools and will certainly help in addressing fundamental
      biological questions and understanding systems as a whole. AVAILABILITY: The
      graphical tools described in this paper are implemented in the freely available R
      package mixOmics and in its associated web application.

PMID- 23148524
TI  - A homozygous mutation of voltage-gated sodium channel beta(I)  gene SCN1B in a
      patient with Dravet syndrome.
AB  - Dravet syndrome is a severe form of epileptic encephalopathy characterized by
      early onset epileptic seizures followed by ataxia and cognitive decline.
      Approximately 80% of patients with Dravet syndrome have been associated with
      heterozygous mutations in SCN1A gene encoding voltage-gated sodium channel (VGSC)
      alpha(I)  subunit, whereas a homozygous mutation (p.Arg125Cys) of SCN1B gene
      encoding VGSC beta(I)  subunit was recently described in a patient with Dravet
      syndrome. To further examine the involvement of homozygous SCN1B mutations in the
      etiology of Dravet syndrome, we performed mutational analyses on SCN1B in 286
      patients with epileptic disorders, including 67 patients with Dravet syndrome who
      have been negative for SCN1A and SCN2A mutations. In the cohort, we found one
      additional homozygous mutation (p.Ile106Phe) in a patient with Dravet syndrome.
      The identified homozygous SCN1B mutations indicate that SCN1B is an etiologic
      candidate underlying Dravet syndrome.

PMID- 23148525
TI  - Communication access to businesses and organizations for people with complex
      communication needs.
AB  - Human rights legislation and anti-discrimination and accessibility laws exist in
      many countries and through international conventions and treaties. To varying
      degrees, these laws protect the rights of people with disabilities to full and
      equal access to goods and services. Yet, the accessibility requirements of people
      with complex communication needs (CCN) are not well represented in the existing
      accessibility literature. This article describes the results of surveys completed
      by disability service providers and individuals with CCN due to cerebral palsy,
      developmental delay, and acquired disabilities. It identifies accessibility
      requirements for people with CCN for face-to-face communication; comprehension of
      spoken language; telephone communication; text and print-based communication;
      Internet, email, and social media interactions; and written communication.
      Recommendations are made for communication accessibility accommodations in
      regulations, guidelines, and practices.

PMID- 23148526
TI  - Mycotoxins in the environment: II. Occurrence and origin in Swiss river waters.
AB  - Thirty-three different mycotoxins were surveyed over nearly two years in a
      typical Swiss wastewater treatment plant (WWTP), as well as in Swiss midland
      rivers. Out of these, 3-acetyl-deoxynivalenol, deoxynivalenol (DON), nivalenol
      (NIV), and beauvericin (BEA), were detected. DON was quantified in all WWTP
      effluent grab samples with a maximum concentration of 73.4 ng/L, while the lowest
      concentration was observed for BEA with 1.3 ng/L. NIV was detected in about 37%,
      the other three compounds in 9-36% of the weekly or fortnightly integrated flow
      proportional river water samples. Concentrations were river discharge dependent,
      with higher numbers in smaller rivers, but mostly in the very low ng/L-range,
      with a maximum of 24.1, and 19.0 ng/L for NIV and DON, respectively. While NIV
      and DON prevailed in summer and autumn, BEA occurred mostly during winter. Summer
      and autumn seasonal load fractions were, however, not correlating with other
      river basin parameters indicative of the probably most obvious seasonal input
      source, that is, Fusarium graminearum infected wheat crop areas. Nevertheless,
      together with WWTP effluents, these two sources largely explained the loads of
      mycotoxins quantified in river waters. The ecotoxicological relevance of
      mycotoxins as newly identified aquatic micropollutants has yet to be assessed.

PMID- 23148527
TI  - An enantioselective total synthesis of helioporins C and E.
AB  - A short and enantioselective total synthesis of helioporins C and E, which are
      bioactive marine diterpenes containing a serrulatane or amphilectane skeleton,
      was elaborated. The chirogenic step, i.e. a Cu(I)-catalyzed allylic alkylation of
      a cinnamyl chloride with methylmagnesium bromide, proceeded with virtually
      complete enantioselectivity (99% ee) in the presence of a chiral phosphine
      phosphite ligand. The other stereocenters were diastereoselectively established
      through Me(2)AlCl-mediated cationic cyclization and Ir-catalyzed hydrogenation.

PMID- 23148528
TI  - A versatile approach to organic photovoltaics evaluation using white light pulse
      and microwave conductivity.
AB  - State-of-the-art low band gap conjugated polymers have been investigated for
      application in organic photovoltaic cells (OPVs) to achieve efficient conversion
      of the wide spectrum of sunlight into electricity. A remarkable improvement in
      power conversion efficiency (PCE) has been achieved through the use of innovative
      materials and device structures. However, a reliable technique for the rapid
      screening of the materials and processes is a prerequisite toward faster
      development in this area. Here we report the realization of such a versatile
      evaluation technique for bulk heterojunction OPVs by the combination of time
      resolved microwave conductivity (TRMC) and submicrosecond white light pulse from
      a Xe-flash lamp. Xe-flash TRMC allows examination of the OPV active layer without
      requiring fabrication of the actual device. The transient photoconductivity
      maxima, involving information on generation efficiency, mobility, and lifetime of
      charge carriers in four well-known low band gap polymers blended with phenyl
      C(61)-butyric acid methyl ester (PCBM), were confirmed to universally correlate
      with the PCE divided by the open circuit voltage (PCE/V(oc)), offering a facile
      way to predict photovoltaic performance without device fabrication.

PMID- 23148529
TI  - Opportunities with fabric composites as unique flexible substrates.
AB  - Flexible substrates enable new capabilities in applications ranging from
      electronics to biomedical devices. To provide a new platform for these
      applications, we investigate a composite material consisting of rigid fiber
      fabrics impregnated with soft elastomers, offering the ability to create load
      bearing, yet flexible substrates. We demonstrate an integrated and facile one
      step imprint lithographic patterning method on a number of fabrics and resins.
      Furthermore, the bending and tensile properties were examined to compare the
      composites to other flexible materials such as PET and cellulose paper. Carbon
      fiber composites possess a higher tensile modulus than PET while retaining almost
      an order of magnitude lower bending modulus. Fabric composites can also have
      anisotropic mechanical properties not observed in homogeneous materials. Finally,
      we provide a discussion of these anisotropic mechanical responses and their
      potential use in flexible applications.

PMID- 23148530
TI  - Time varying prediction of thoughts of death and suicidal ideation in
      adolescents: weekly ratings over 6-month follow-up.
AB  - Suicidal ideation (SI) and thoughts of death are often experienced as
      fluctuating; therefore a dynamic representation of this highly important
      indicator of suicide risk is warranted. Theoretical accounts have suggested that
      affective, behavioral, and interpersonal factors may influence the experience of
      thoughts of death/SI. This study aimed to examine the prospective and dynamic
      impact of these constructs in relation to thoughts of death and SI. We assessed
      adolescents with a recent hospitalization for elevated suicide risk over 6
      months. Using the methodology of the Longitudinal Interval Follow-Up Evaluation,
      weekly ratings for SI, course of depressive illness, affect sensitivity, negative
      affect intensity, behavioral dysregulation, peer invalidation, and family
      invalidation were obtained. Using multilevel modeling, results indicated that (a)
      same-week ratings between these constructs and SI were highly correlated at
      baseline and throughout follow-up; (b) baseline ratings of affect sensitivity,
      behavioral dysregulation, and peer invalidation were positive prospective
      predictors of SI at any week of follow-up; (c) weekly ratings of each of these
      constructs had significant associations with next-week ratings of SI; and (d)
      ratings of SI had positive significant associations with next-week ratings on
      each of the constructs. These results suggest that affective sensitivity,
      behavioral dysregulation, peer invalidation, and SI are highly associated with SI
      levels both chronically (over months) and acutely (one week to the next), whereas
      depression, negative affect intensity, and family invalidation were more acutely
      predictive of SI. Elevated SI may then aggravate all these factors in a
      reciprocal manner. 

PMID- 23148532
TI  - A novel DNA binding mechanism for maf basic region-leucine zipper factors
      inferred from a MafA-DNA complex structure and binding specificities.
AB  - MafA is a proto-oncoprotein and is critical for insulin gene expression in
      pancreatic beta-cells. Maf proteins belong to the AP1 superfamily of basic region
      leucine zipper (bZIP) transcription factors. Residues in the basic helix and an
      ancillary N-terminal domain, the Extended Homology Region (EHR), endow maf
      proteins with unique DNA binding properties: binding a 13 bp consensus site
      consisting of a core AP1 site (TGACTCA) flanked by TGC sequences and binding DNA
      stably as monomers. To further characterize maf DNA binding, we determined the
      structure of a MafA-DNA complex. MafA forms base-specific hydrogen bonds with the
      flanking G(-5)C(-4) and central C(0)/G(0) bases, but not with the core-TGA bases.
      However, in vitro binding studies utilizing a pulse-chase electrophoretic
      mobility shift assay protocol revealed that mutating either the core-TGA or
      flanking-TGC bases dramatically increases the binding off rate. Comparing the
      known maf structures, we propose that DNA binding specificity results from
      positioning the basic helix through unique phosphate contacts. The EHR does not
      contact DNA directly but stabilizes DNA binding by contacting the basic helix.
      Collectively, these results suggest a novel multistep DNA binding process
      involving a conformational change from contacting the core-TGA to contacting the
      flanking-TGC bases.

PMID- 23148531
TI  - Human-specific protein isoforms produced by novel splice sites in the human
      genome after the human-chimpanzee divergence.
AB  - BACKGROUND: Evolution of splice sites is a well-known phenomenon that results in
      transcript diversity during human evolution. Many novel splice sites are derived
      from repetitive elements and may not contribute to protein products. Here, we
      analyzed annotated human protein-coding exons and identified human-specific
      splice sites that arose after the human-chimpanzee divergence. RESULTS: We
      analyzed multiple alignments of the annotated human protein-coding exons and
      their respective orthologous mammalian genome sequences to identify 85 novel
      splice sites (50 splice acceptors and 35 donors) in the human genome. The novel
      protein-coding exons, which are expressed either constitutively or alternatively,
      produce novel protein isoforms by insertion, deletion, or frameshift. We found
      three cases in which the human-specific isoform conferred novel molecular
      function in the human cells: the human-specific IMUP protein isoform induces
      apoptosis of the trophoblast and is implicated in pre-eclampsia; the
      intronization of a part of SMOX gene exon produces inactive spermine oxidase; the
      human-specific NUB1 isoform shows reduced interaction with ubiquitin-like
      proteins, possibly affecting ubiquitin pathways. CONCLUSIONS: Although the
      generation of novel protein isoforms does not equate to adaptive evolution, we
      propose that these cases are useful candidates for a molecular functional study
      to identify proteomic changes that might bring about novel phenotypes during
      human evolution.

PMID- 23148533
TI  - The structure of psychological life satisfaction: insights from farmers and a
      general community sample in Australia.
AB  - BACKGROUND: Psychological life satisfaction is a robust predictor of wellbeing.
      Public health measures to improve wellbeing would benefit from an understanding
      of how overall life satisfaction varies as a function of satisfaction with
      multiple life domains, an area that has been little explored. We examine a sample
      of drought-affected Australian farmers and a general community sample of
      Australians to investigate how domain satisfaction combines to form psychological
      satisfaction. In particular, we introduce a way of statistically testing for the
      presence of "supra-domains" of satisfaction to propose a novel way of examining
      the composition of psychological life satisfaction to gain insights for health
      promotion and policy. METHODS: Covariance between different perceptions of life
      domain satisfaction was identified by conducting correlation, regression, and
      exploratory factor analyses on responses to the Personal Wellbeing Index.
      Structural equations modelling was then used to (a) validate satisfaction supra
      domain constructs emerging from different perceptions of life domain
      satisfaction, and (b) model relationships between supra-domains and an explicit
      measure of psychological life satisfaction. RESULTS: Perceived satisfaction with
      eight different life domains loaded onto a single unitary satisfaction construct
      adequately in each sample. However, in both samples, different domains better
      loaded onto two separate but correlated constructs ('supra-domains'):
      "satisfaction with connectedness" and "satisfaction with efficacy". Modelling
      reciprocal pathways between these supra-domains and an explicit measure of
      psychological life satisfaction revealed that efficacy mediated the link between
      connectedness and psychological satisfaction. CONCLUSIONS: If satisfaction with
      connectedness underlies satisfaction with efficacy (and thus psychological
      satisfaction), a novel insight for health policy emerges: psychological life
      satisfaction, a vital part of wellbeing, can potentially be enhanced by
      strengthening individuals' connectedness to community. This may be particularly
      important and efficacious for vulnerable populations.

PMID- 23148534
TI  - Nanoparticle drug delivery: focusing on the therapeutic cargo.

PMID- 23148536
TI  - Focus on the development of computer-aided nanomedicine design.

PMID- 23148538
TI  - Localized profiling of multiple neurotransmitter concentrations.

PMID- 23148535
TI  - Biocompatible nanopolymers: the next generation of breast cancer treatment?

PMID- 23148539
TI  - Leading the way in biomedical engineering: an interview with Robert Langer.
      Interview by Hannah Stanwix, Commissioning Editor.
AB  - Professor Robert Langer obtained his Bachelor's Degree in Chemical Engineering
      from Cornell University (NY, USA) in 1970. He received his Sc.D. from the
      Massachusetts Institute of Technology (MA, USA) in 1974. He is currently the
      David H Koch Institute Professor at the Massachusetts Institute of Technology.
      Professor Langer is a member of the Institute of Medicine of the National Academy
      of Sciences, the National Academy of Engineering and the National Academy of
      Sciences. At the age of 43 he was the youngest person in history to be elected to
      all three United States National Academies. Throughout his career, Professor
      Langer has received over 200 awards including, notably, the Charles Stark Draper
      Prize (considered the equivalent of the Nobel Prize for engineers), the 2008
      Millennium Prize, the 2006 United States National Medal of Science and the 2012
      Priestley Medal. In 1996 he was awarded the Gairdner Foundation International
      Award (the only engineer ever to have been awarded this accolade). Professor
      Langer has also been the recipient of the Lemelson-MIT prize, which he was
      awarded with for being "one of history's most prolific inventors in medicine."
      Professor Langer was selected by Time Magazine in 2001 as one of the 100 most
      important people in the USA. He has received honorary degrees from several
      universities worldwide, including Harvard University (MA, USA), the Mt. Sinai
      School of Medicine (NY, USA), Yale University (CT, USA), the ETH Zurich (Zurich,
      Switzerland), the Technion-Israel Institute of Technology (Haifa, Israel), the
      Hebrew University of Jerusalem (Israel), the Universite Catholique de Louvain
      (Louvain-La-Neuve, Belgium), Rensselaer Polytechnic Institute (NY, USA),
      Willamette University (OR, USA), the University of Liverpool (Liverpool, UK),
      Bates College (ME, USA), the University of Nottingham (Nottingham, UK), Albany
      Medical College (NY, USA), Pennsylvania State University (PA, USA), Northwestern
      University (IL, USA) and Uppsala University (Uppsala, Sweden), and was awarded
      with the University of California San Francisco Medal in 2009. Professor Langer
      has founded over 20 biotechnology companies and authored more than 1175 articles.
      He has over 800 issued or pending patents. Professor Langer is the most cited
      engineer in history.

PMID- 23148540
TI  - Nanodelivery strategies in cancer chemotherapy: biological rationale and
      pharmaceutical perspectives.
AB  - Nanotechnology is revolutionizing our approach to drug delivery, a key
      determinant of drug efficacy. Here, we present cancer drug delivery strategies
      that exploit nanotechnology, providing first an overview of tumor biology aspects
      that critically affect the design of drug delivery carriers, namely the enhanced
      permeability and retention effect, the lower tumor extracellular pH and tumor
      specific antigens. In general, nanoscience-based approaches have circumvented
      limitations in the delivery of cancer therapeutics, related to their poor aqueous
      solubility and toxicity issues with conventional vehicles and resulted in
      improved pharmacokinetics and biodistribution. Included in the discussion are
      promising examples and pharmaceutical perspectives on liposomes, nanoemulsions,
      solid lipid nanoparticles, polymeric nanoparticles, dendrimers, carbon nanotubes
      and magnetic nanoparticles. As the cardinal features of the ideal multifunctional
      cancer drug nanocarrier are becoming clear, and drug development challenges are
      proactively addressed, we anticipate that future advances will enhance
      therapeutic outcomes by refining the delivery and targeting of complex payloads.

PMID- 23148541
TI  - Enhancing immunogenicity and cross-reactivity of HIV-1 antigens by in vivo
      targeting to dendritic cells.
AB  - Current retroviral treatments have reduced AIDS to a chronic disease for most
      patients. However, given drug-related side effects, the emergence of drug
      resistant strains and the persistence of viral replication, the development of
      alternative treatments is a pressing need. This review focuses on recent
      developments in HIV immunotherapy treatments, with particular emphasis on current
      vaccination strategies for optimizing the induction of an effective immune
      response by the recruitment of dendritic cells. In addition to cell-based
      therapies, targeted strategies aiming to deliver synthetic HIV peptides to
      dendritic cell-specific receptors in vivo will be discussed.

PMID- 23148542
TI  - Microfabricated magnetic structures for future medicine: from sensors to cell
      actuators.
AB  - In this review, we discuss the prospective medical application of magnetic
      carriers microfabricated by top-down techniques. Physical methods allow the
      fabrication of a variety of magnetic structures with tightly controlled magnetic
      properties and geometry, which makes them very attractive for a cost-efficient
      mass-production in the fast growing field of nanomedicine. Stand-alone fabricated
      particles along with integrated devices combining lithographically defined
      magnetic structures and synthesized magnetic tags will be considered.
      Applications of microfabricated multifunctional magnetic structures for future
      medicinal purposes range from ultrasensitive in vitro diagnostic bioassays, DNA
      sequencing and microfluidic cell sorting to magnetomechanical actuation, cargo
      delivery, contrast enhancement and heating therapy.

PMID- 23148543
TI  - Living cell study at the single-molecule and single-cell levels by atomic force
      microscopy.
AB  - Atomic force microscopy (AFM) has been emerging as a multifunctional molecular
      tool in nanobiology and nanomedicine. This review summarizes the recent advances
      in AFM study of living mammalian cells at the single-molecule and single-cell
      levels. Besides nanoscale imaging of cell membrane structure, AFM-based force
      measurements on living cells are mainly discussed. These include the development
      and application of single-molecule force spectroscopy to investigate ligand
      receptor binding strength and dissociation dynamics, and the characterization of
      cell mechanical properties in a physiological environment. Molecular manipulation
      of cells by AFM to change the cellular process is also described. Living-cell AFM
      study offers a new approach to understand the molecular mechanisms of cell
      function, disease development and drug effect, as well as to develop new
      strategies to achieve single-cell-based diagnosis.

PMID- 23148545
TI  - Obesity, metabolic syndrome, impaired fasting glucose, and microvascular
      dysfunction: a principal component analysis approach.
AB  - BACKGROUND: We aimed to evaluate the multivariate association between functional
      microvascular variables and clinical-laboratorial-anthropometrical measurements.
      METHODS: Data from 189 female subjects (34.0 +/- 15.5 years, 30.5 +/- 7.1 kg/m2),
      who were non-smokers, non-regular drug users, without a history of diabetes
      and/or hypertension, were analyzed by principal component analysis (PCA). PCA is
      a classical multivariate exploratory tool because it highlights common variation
      between variables allowing inferences about possible biological meaning of
      associations between them, without pre-establishing cause-effect relationships.
      In total, 15 variables were used for PCA: body mass index (BMI), waist
      circumference, systolic and diastolic blood pressure (BP), fasting plasma
      glucose, levels of total cholesterol, high-density lipoprotein cholesterol (HDL
      c), low-density lipoprotein cholesterol (LDL-c), triglycerides (TG), insulin, C
      reactive protein (CRP), and functional microvascular variables measured by
      nailfold videocapillaroscopy. Nailfold videocapillaroscopy was used for direct
      visualization of nutritive capillaries, assessing functional capillary density,
      red blood cell velocity (RBCV) at rest and peak after 1 min of arterial occlusion
      (RBCV(max)), and the time taken to reach RBCV(max) (TRBCV(max)). RESULTS: A total
      of 35% of subjects had metabolic syndrome, 77% were overweight/obese, and 9.5%
      had impaired fasting glucose. PCA was able to recognize that functional
      microvascular variables and clinical-laboratorial-anthropometrical measurements
      had a similar variation. The first five principal components explained most of
      the intrinsic variation of the data. For example, principal component 1 was
      associated with BMI, waist circumference, systolic BP, diastolic BP, insulin, TG,
      CRP, and TRBCV(max) varying in the same way. Principal component 1 also showed a
      strong association among HDL-c, RBCV, and RBCV(max), but in the opposite way.
      Principal component 3 was associated only with microvascular variables in the
      same way (functional capillary density, RBCV and RBCV(max)). Fasting plasma
      glucose appeared to be related to principal component 4 and did not show any
      association with microvascular reactivity. CONCLUSIONS: In non-diabetic female
      subjects, a multivariate scenario of associations between classic clinical
      variables strictly related to obesity and metabolic syndrome suggests a
      significant relationship between these diseases and microvascular reactivity.

PMID- 23148546
TI  - Aromatase inhibitors associated with knee subchondral bone expansion without
      cartilage loss.
AB  - BACKGROUND: The profound estrogen depletion caused by aromatase inhibitors (AIs)
      is associated with musculoskeletal symptoms, but the underlying pathophysiology
      remains unclear. OBJECTIVE: To assess the effects of AI therapy on structural
      changes in knee cartilage and subchondral bone over 2 years in postmenopausal
      women. Setting and participants Thirty women with breast cancer, mean age 58.5
      (standard deviation +/- 5.6) years and 62 healthy controls, mean age 56.5
      (standard deviation +/- 4.6) years. MAIN OUTCOME MEASURES: Annualized changes in
      tibial cartilage volume and subchondral bone area, and worsening of tibiofemoral
      cartilage defects from paired knee magnetic resonance imaging 2 years apart were
      compared between the two groups. RESULTS: The AI-treated women had significantly
      greater expansion of the tibial plateau than the control group. The mean
      annualized differences, after adjusting for age, body mass index and baseline
      bone area, were 22.1 mm(2) (95% confidence interval (CI) 7.6-36.6, p = 0.003) for
      the medial tibial plateau and 19.1 mm(2) (95% CI 9.6-28.5, p < 0.001) for the
      lateral tibial plateau. The annual change in tibial cartilage volume and the
      worsening of cartilage defects did not differ between women taking AI therapy and
      controls. CONCLUSIONS: AI therapy is associated with knee subchondral bone
      expansion knee with no effect on knee cartilage in postmenopausal women without
      pre-existing joint symptoms. This suggests the effect of severe estrogen
      depletion on knee is on bone, with the tibial bone expansion most likely a
      response to mechanical load in the setting of bone loss. Whether this then
      results in an increased risk of knee osteoarthritis will need to be determined.

PMID- 23148547
TI  - The mediating role of psychological need satisfaction in relationships between
      types of passion for sport and athlete burnout.
AB  - Research indicates that obsessive and harmonious passion can explain variability
      in burnout through various mediating processes (e.g., Vallerand, Paquet,
      Phillippe, & Charest, 2010). The current study extended previous research
      (Curran, Appleton, Hill, & Hall, 2011; Gustafsson, Hassmen, & Hassmen, 2011) by
      testing a model in which the effects of passion for sport on athlete burnout were
      mediated by psychological need satisfaction. One hundred and seventy-three
      academy soccer players completed self-report measures of passion for sport,
      psychological need satisfaction, and athlete burnout. Results indicated that
      psychological need satisfaction mediated the relationship between harmonious
      passion and athlete burnout but not obsessive passion and athlete burnout. The
      findings indicate that the inverse relationship between harmonious passion and
      burnout can be explained by higher levels of psychological need satisfaction.
      However, this was not the case for obsessive passion, which was not associated
      with psychological need satisfaction or most symptoms of athlete burnout.

PMID- 23148549
TI  - DNA methylation of the IGF2/H19 imprinting control region and adiposity
      distribution in young adults.
AB  - BACKGROUND: The insulin-like growth factor 2 (IGF2) and H19 imprinted genes
      control growth and body composition. Adverse in-utero environments have been
      associated with obesity-related diseases and linked with altered DNA methylation
      at the IGF2/H19 locus. Postnatally, methylation at the IGF2/H19 imprinting
      control region (ICR) has been linked with cerebellum weight. We aimed to
      investigate whether decreased IGF2/H19 ICR methylation is associated with
      decreased birth and childhood anthropometry and increased contemporaneous
      adiposity.DNA methylation in peripheral blood (n = 315) at 17 years old was
      measured at 12 cytosine-phosphate-guanine sites (CpGs), analysed as Sequenom
      MassARRAY EpiTYPER units within the IGF2/H19 ICR. Birth size, childhood head
      circumference (HC) at six time-points and anthropometry at age 17 years were
      measured. DNA methylation was investigated for its association with anthropometry
      using linear regression. RESULTS: The principal component of IGF2/H19 ICR DNA
      methylation (representing mean methylation across all CpG units) positively
      correlated with skin fold thickness (at four CpG units) (P-values between 0.04 to
      0.001) and subcutaneous adiposity (P = 0.023) at age 17, but not with weight,
      height, BMI, waist circumference or visceral adiposity. IGF2/H19 methylation did
      not associate with birth weight, length or HC, but CpG unit 13 to 14 methylation
      was negatively associated with HC between 1 and 10 years. beta-coefficients of
      four out of five remaining CpG units also estimated lower methylation with
      increasing childhood HC. CONCLUSIONS: As greater IGF2/H19 methylation was
      associated with greater subcutaneous fat measures, but not overall, visceral or
      central adiposity, we hypothesize that obesogenic pressures in youth result in
      excess fat being preferentially stored in peripheral fat depots via the IGF2/H19
      domain. Secondly, as IGF2/H19 methylation was not associated with birth size but
      negatively with early childhood HC, we hypothesize that the HC may be a more
      sensitive marker of early life programming of the IGF axis and of fetal
      physiology than birth size. To verify this, investigations of the dynamics of
      IGF2/H19 methylation and expression from birth to adolescence are required.

PMID- 23148550
TI  - Use of cross-border healthcare services among ethnic Danes, Turkish immigrants
      and Turkish descendants in Denmark: a combined survey and registry study.
AB  - BACKGROUND: Healthcare obtained abroad may conflict with care received in the
      country of residence. A special concern for immigrants has been raised as they
      may have stronger links to healthcare services abroad. Our objective was to
      investigate use of healthcare in a foreign country in Turkish immigrants, their
      descendants, and ethnic Danes. METHODS: The study was based on a nationwide
      survey in 2007 with 372 Turkish immigrants, 496 descendants, and 1,131 ethnic
      Danes aged 18-66. Data were linked to registry data on socioeconomic factors.
      Using logistic regression models, use of doctor, specialist doctor, hospital,
      dentist in a foreign country as well as medicine from abroad were estimated.
      Analyses were adjusted for socioeconomic factors and health symptoms. RESULTS:
      Overall, 26.6% among Turkish immigrants made use of cross-border healthcare,
      followed by 19.4% among their descendants to 6.7% among ethnic Danes. Using
      logistic regression models with ethnic Danes as the reference group, Turkish
      immigrants were seen to have made increased use of general practitioners,
      specialist doctors, hospitals, and dentists in a foreign country (odds ratio
      (OR), 5.20-6.74), while Turkish descendants had made increased use of specialist
      doctors (OR, 4.97) and borderline statistically significant increased use of
      hospital (OR, 2.48) and dentist (OR, 2.17) but not general practitioners. For
      medicine, we found no differences among the men, but women with an immigrant
      background made considerably greater use, compared with ethnic Danish women.
      Socioeconomic position and health symptoms had a fairly explanatory effect on the
      use in the different groups. CONCLUSIONS: Use of cross-border healthcare may have
      consequences for the continuity of care, including conflicts in the medical
      treatment, for the patient. Nonetheless, it may be aligned with the patient's
      preferences and thereby beneficial for the patient. We need more information
      about reasons for obtaining cross-border healthcare among immigrants residing in
      European countries, and the consequences for the patient and the healthcare
      systems, including the quality of care. The Danish healthcare system needs to be
      aware of the significant healthcare consumption by immigrants, especially
      medicine among women, outside Denmark's borders.

PMID- 23148551
TI  - Effect of contingent electrical stimulation on jaw muscle activity during sleep:
      a pilot study with a randomized controlled trial design.
AB  - OBJECTIVE: To determine the effect of contingent electrical stimulation (CES) on
      jaw muscle activity during sleep in a double-blinded randomized controlled trial
      (RCT). MATERIALS AND METHODS: Eleven patients with myofascial TMD (mean age 37
      years) and with a clinical diagnosis of bruxism were included. EMG activity
      (Grindcare(r)) was recorded from the anterior temporalis muscle during sleep and
      analyzed online. Jaw muscle activity related to clenching or grinding triggered
      an electrical square-wave pulse train (450 ms) adjusted to a clear, but non
      painful intensity. TMD patients were randomized into two groups: active treatment
      with CES or no CES (placebo). Number of EMG episodes/hour sleep was the primary
      outcome parameter. The following variables were assessed as secondary outcome
      parameters; number of painful muscles, maximum pain-free jaw opening,
      characteristic pain intensity, depression scores and Oral Health Impact Profile
      scores. Numerical Rating Scale scores for self-reported pain and muscle tension
      were registered for at least 4 nights per week during the experiment. RESULTS:
      The number of EMG episodes/hour sleep was significantly reduced (52 +/- 12%) in
      the CES group during the sessions with CES (ANOVA: p = 0.021) compared to
      baseline. There were no significant differences in the secondary outcome
      parameters (ANOVA: p > 0.513) or pain or muscle tension scores between groups (p
      = 0.645). The average duration of sleep hours during the nights with and without
      CES was not significantly different (p = 0.646). CONCLUSIONS: These results
      demonstrate a significant inhibitory effect of CES on jaw muscle EMG activity
      during sleep in a RCT, but with no effects on self-reported pain.

PMID- 23148554
TI  - Ferroferric oxide/multiwalled carbon nanotube vs polyaniline/ferroferric
      oxide/multiwalled carbon nanotube multiheterostructures for highly effective
      microwave absorption.
AB  - Light-weight nanocomposites filled with carbon nanotubes (CNTs) are developed for
      their significant potentials in electromagnetic shielding and attenuation for
      wide applications in electronics, communication devices, and specific parts in
      aircrafts and vehicles. Specifically, the introduction of a second phase
      into/onto CNTs for achieving CNT-based heterostructures has been widely pursued
      due to the enhancement in either dielectric loss or magnetic loss. In this work,
      ferroferric oxide (Fe(3)O(4)) was selected as the phase in multiwalled carbon
      nanotube (MWCNT)-based composites for enhancing magnetic properties to obtain
      improved electromagnetic attenuation. A direct comparison between the two-phase
      heterostructures (Fe(3)O(4)/MWCNTs) and polyaniline (PANI) coated
      Fe(3)O(4)/MWCNTs, namely, three-phase heterostructures (PANI/Fe(3)O(4)/MWCNTs),
      was made to investigate the interface influences of Fe(3)O(4) and PANI on the
      complex permittivity and permeability separately. Compared to
      PANI/Fe(3)O(4)/MWCNTs, Fe(3)O(4)/MWCNTs exhibited enhanced magnetic properties
      coupled with increased dielectric properties. Interfaces between MWCNTs and
      heterostructures were found to play a role in the corresponding properties. The
      evaluation of microwave absorption of their wax composites was carried out, and
      the comparison between Fe(3)O(4)/MWCNTs and PANI/Fe(3)O(4)/MWCNTs with respect to
      highly efficient microwave absorption and effective absorption bandwidth was
      discussed.

PMID- 23148553
TI  - Potential pathways from stigmatization and externalizing behavior to anger and
      dating aggression in sexually abused youth.
AB  - Although experiencing childhood sexual abuse (CSA) puts youth at risk for
      involvement in relationship violence, research is limited on the potential
      pathways from CSA to subsequent dating aggression. The current study examined
      prospective pathways from externalizing behavior problems and stigmatization
      (abuse-specific shame and self-blame attributions) to anger and dating
      aggression. One hundred sixty youth (73% female, 69% ethnic/racial minorities)
      with confirmed CSA histories were interviewed at the time of abuse discovery (T1,
      when they were 8-15 years of age), and again 1 and 6 years later (T2 and T3).
      Externalizing behavior and abuse-specific stigmatization were assessed at T1 and
      T2. Anger and dating aggression were assessed at T3. The structural equation
      model findings supported the proposed relations from stigmatization following the
      abuse to subsequent dating aggression through anger. Only externalizing behavior
      at T1 was related to later dating aggression, and externalizing was not related
      to subsequent anger. This longitudinal research suggests that clinical
      interventions for victims of CSA be sensitive to the different pathways by which
      youth come to experience destructive conflict behavior in their romantic
      relationships.

PMID- 23148552
TI  - Association studies of the copy-number variable beta-defensin cluster on 8p23.1
      in adenocarcinoma and chronic pancreatitis.
AB  - BACKGROUND: Human beta-defensins are a family of antimicrobial peptides located
      at the mucosal surface. Both sequence multi-site variations (MSV) and copy-number
      variants (CNV) of the defensin-encoding genes are associated with increased risk
      for various diseases, including cancer and inflammatory conditions such as
      psoriasis and acute pancreatitis. In a case-control study, we investigated the
      association between MSV in DEFB104 as well as defensin gene (DEF) cluster copy
      number (CN), and pancreatic ductal adenocarcinoma (PDAC) and chronic pancreatitis
      (CP). RESULTS: Two groups of PDAC (N=70) and CP (N=60) patients were compared to
      matched healthy control groups CARLA1 (N=232) and CARLA2 (N=160), respectively.
      Four DEFB104 MSV were haplotyped by PCR, cloning and sequencing. DEF cluster CN
      was determined by multiplex ligation-dependent probe amplification.Neither the
      PDAC nor the CP cohorts show significant differences in the DEFB104 haplotype
      distribution compared to the respective control groups CARLA1 and CARLA2,
      respectively.The diploid DEF cluster CN exhibit a significantly different
      distribution between PDAC and CARLA1 (Fisher's exact test P=0.027), but not
      between CP and CARLA2 (P=0.867). CONCLUSION: Different DEF cluster b CN
      distribution between PDAC patients and healthy controls indicate a potential
      protective effect of higher CNs against the disease.

PMID- 23148555
TI  - Prevalence of neurocysticercosis among people with epilepsy in rural areas of
      Burkina Faso.
AB  - PURPOSE: To estimate the lifetime prevalence of neurocysticercosis (NCC)
      associated epilepsy and the proportion of NCC among people with epilepsy in three
      Burkina Faso villages. METHODS: Three villages were selected to represent three
      types of pig-rearing methods: (1) Batondo, where pigs are left to roam; (2)
      Pabre, where pigs are mostly tethered or penned; and (3) Nyonyogo, where the
      majority of residents are Muslim and few pigs are raised. In Batondo and
      Nyonyogo, all concessions (a group of several households) were included. Half of
      the concessions in Pabre were randomly chosen. All households of selected
      concessions were included, and one person per household was randomly selected for
      epilepsy screening and serologic testing for cysticercosis. Self-reported cases
      of epilepsy were also examined and confirmed cases included in analyses other
      than the estimate of NCC-associated epilepsy prevalence. Epilepsy was defined as
      ever having had more than one episode of unprovoked seizures. Individuals with
      medically confirmed epilepsy had a computerized tomography (CT) scan of the brain
      before and after contrast medium injection. The diagnosis of NCC was made using a
      modification of the criteria of Del Brutto et al. KEY FINDINGS: Thirty-nine (4%)
      of 888 randomly selected villagers and 33 (94%) of 35 self-reported seizures
      cases were confirmed to have epilepsy by medical examination. Among the 68
      participants with epilepsy who had a CT scan, 20 patients were diagnosed with
      definitive or probable NCC for a proportion of 46.9% (95% confidence interval
      [CI] 30.2-64.1) in Batondo and 45.5% (95% CI 19.0-74.1) in Pabre. No cases of NCC
      were identified in Nyonyogo. SIGNIFICANCE: All the definitive and probable cases
      of NCC were from the two villages where pig breeding is common. Prevention
      policies intended to reduce the burden of epilepsy in this country should include
      measures designed to interrupt the life cycle of Taenia solium.

PMID- 23148557
TI  - 15 Million preterm births annually: what has changed this year?
AB  - Each year, more than 1 in 10 of the world's babies are born preterm, resulting in
      15 million babies born too soon. World Prematurity Day, November 17, is a global
      effort to raise awareness about prematurity. This past year, there has been
      increased awareness of the problem, through new data and evidence, global
      partnership and country champions. Actions to improve care would save hundreds of
      thousands of babies born too soon from death and disability. Accelerated
      prevention requires urgent research breakthroughs.

PMID- 23148556
TI  - School closure as an influenza mitigation strategy: how variations in legal
      authority and plan criteria can alter the impact.
AB  - BACKGROUND: States' pandemic influenza plans and school closure statutes are
      intended to guide state and local officials, but most faced a great deal of
      uncertainty during the 2009 influenza H1N1 epidemic. Questions remained about
      whether, when, and for how long to close schools and about which agencies and
      officials had legal authority over school closures. METHODS: This study began
      with analysis of states' school-closure statutes and pandemic influenza plans to
      identify the variations among them. An agent-based model of one state was used to
      represent as constants a population's demographics, commuting patterns, work and
      school attendance, and community mixing patterns while repeated simulations
      explored the effects of variations in school closure authority, duration, closure
      thresholds, and reopening criteria. RESULTS: The results show no basis on which
      to justify statewide rather than school-specific or community-specific authority
      for school closures. Nor do these simulations offer evidence to require school
      closures promptly at the earliest stage of an epidemic. More important are
      criteria based on monitoring of local case incidence and on authority to sustain
      closure periods sufficiently to achieve epidemic mitigation. CONCLUSIONS: This
      agent-based simulation suggests several ways to improve statutes and influenza
      plans. First, school closure should remain available to state and local
      authorities as an influenza mitigation strategy. Second, influenza plans need not
      necessarily specify the threshold for school closures but should clearly define
      provisions for early and ongoing local monitoring. Finally, school closure
      authority may be exercised at the statewide or local level, so long as decisions
      are informed by monitoring incidence in local communities and schools.

PMID- 23148558
TI  - Self-reported rather than registered cancer is associated with psychosocial
      strain.
AB  - BACKGROUND: Individuals with only a subjective experience of cancer may conceal
      severe psychological distress and act like patients with verified disease. The
      purpose of the study was to establish whether some typical psychosocial factors
      may be linked to subjects with registered cancer (confirmed) and also to those
      with self-reported cancer lacking accompanying registered data (non-confirmed).
      METHODS: The material comprised 25,898 working-aged individuals (response rate
      40.0%) in 1998. Of these 19,629 also responded at the follow-up in 2003 (response
      rate 75.8%). The analyses focused on respondents with cancer diagnosis in 2002 or
      earlier according to data of the Finnish Cancer Registry and self-report of
      cancer in 2003 (confirmed) (N=330) and on respondents with self-reported cancer
      only but lacking registered diagnosis (non-confirmed) (N=140). Those who neither
      reported cancer nor had a diagnosis were included as a control group (N=18,299).
      RESULTS: Respondents with confirmed cancer belonged more often to the oldest age
      group than those with non-confirmed cancer. Respondents with non-confirmed cancer
      were more often obese, depressed and reported less social support compared to
      subjects with confirmed cancer. Compared to controls they had a statistically
      significantly increased risk of depression, lower optimism, lower life
      satisfaction, more childhood adversities, more negative life events and less
      social support. CONCLUSIONS: Individuals with only a subjective experience of
      cancer reported more psychosocial strain than those with accompanying registered
      cancer. Self-report of a severe disease like cancer without corresponding
      clinical findings might reflect heavy psychological distress which should be
      taken into consideration in clinical work.

PMID- 23148559
TI  - Exploiting the reversible covalent bonding of boronic acids: recognition,
      sensing, and assembly.
AB  - Boronic acids can interact with Lewis bases to generate boronate anions, and they
      can also bind with diol units to form cyclic boronate esters. Boronic acid based
      receptor designs originated when Lorand and Edwards used the pH drop observed
      upon the addition of saccharides to boronic acids to determine their association
      constants. The inherent acidity of the boronic acid is enhanced when 1,2-, 1,3-,
      or 1,4-diols react with boronic acids to form cyclic boronic esters (5, 6, or 7
      membered rings) in aqueous media, and these interactions form the cornerstone of
      diol-based receptors used in the construction of sensors and separation systems. 
      In addition, the recognition of saccharides through boronic acid complex (or
      boronic ester) formation often relies on an interaction between a Lewis acidic
      boronic acid and a Lewis base (proximal tertiary amine or anion). These
      properties of boronic acids have led to them being exploited in sensing and
      separation systems for anions (Lewis bases) and saccharides (diols).  The fast
      and stable bond formation between boronic acids and diols to form boronate esters
      can serve as the basis for forming reversible molecular assemblies. In spite of
      the stability of the boronate esters' covalent B-O bonds, their formation is
      reversible under certain conditions or under the action of certain external
      stimuli.  The reversibility of boronate ester formation and Lewis acid-base
      interactions has also resulted in the development and use of boronic acids within
      multicomponent systems. The dynamic covalent functionality of boronic acids with
      structure-directing potential has led researchers to develop a variety of self
      organizing systems including macrocycles, cages, capsules, and polymers.  This
      Account gives an overview of research published about boronic acids over the last
      5 years. We hope that this Account will inspire others to continue the work on
      boronic acids and reversible covalent chemistry.

PMID- 23148560
TI  - Proteomic analysis of human blastocoel fluid and blastocyst cells.
AB  - Human embryonic stem cells (hESCs) are derived from the inner cell mass (ICM) of
      the blastocyst and can differentiate into any cell type in the human body. These
      cells hold a great potential for regenerative medicine, but to obtain enough
      cells needed for medical treatment, culture is required on a large scale. In the
      undifferentiated state, hESCs appear to possess an unlimited potential for
      proliferation, but optimal, defined, and safe culture conditions remain a
      challenge. The aim of the present study was to identify proteins in the natural
      environment of undifferentiated hESCs, namely, the blastocoel fluid, which is in
      contact with all the cells in the blastocyst, including hESCs. Fifty-three
      surplus human blastocysts were donated after informed consent, and blastocoel
      fluid was isolated by micromanipulation. Using highly sensitive nano-high
      pressure liquid chromatography-tandem mass spectrometry, 286 proteins were
      identified in the blastocoel fluid and 1,307 proteins in the corresponding cells
      of the blastocyst. Forty-two were previously uncharacterized proteins-8 of these
      originated from the blastocoel fluid. Furthermore, several heat shock proteins
      (Hsp27, Hsp60, Hsc70, and Hsp90) were identified in blastocoel fluid together
      with zona pellucida proteins (ZP2-4), Vitamin D-binding protein, and Retinol
      binding protein 4. Proteins that regulate ciliary assembly and function were also
      identified, including Bardet-Biedl syndrome protein 7. This study has identified
      numerous proteins that cells from the ICM of the human blastocyst are exposed to
      via the blastocoel fluid. These results can be an inspiration for the development
      of improved culture conditions for hESCs.

PMID- 23148561
TI  - Binding of Eu(III) to 1,2-hydroxypyridinone-modified peptide nucleic acids.
AB  - Substitution of a nucleobase pair with a pair of 1,2-hydroxypyridinone (1,2-HOPO)
      ligands in the center of a 10-base-pair peptide nucleic acid (PNA) duplex
      provides a strong binding site for Eu(III) as evidenced by UV thermal melting
      curves, UV titrations, and luminescence spectroscopy. Eu(III) excitation spectra
      and luminescence lifetime data are consistent with Eu(III) bound to both 1,2 HOPO
      ligands in a PNA-HOPO duplex as the major species present in solution.

PMID- 23148563
TI  - Crystal structures of the Helicobacter pylori MTAN enzyme reveal specific
      interactions between S-adenosylhomocysteine and the 5'-alkylthio binding subsite.
AB  - The bacterial 5'-methylthioadenosine/S-adenosylhomocysteine nucleosidase (MTAN)
      enzyme is a multifunctional enzyme that catalyzes the hydrolysis of the N
      ribosidic bond of at least four different adenosine-based metabolites: S
      adenosylhomocysteine (SAH), 5'-methylthioadenosine (MTA), 5'-deoxyadenosine (5'
      DOA), and 6-amino-6-deoxyfutalosine. These activities place the enzyme at the hub
      of seven fundamental bacterial metabolic pathways: S-adenosylmethionine (SAM)
      utilization, polyamine biosynthesis, the purine salvage pathway, the methionine
      salvage pathway, the SAM radical pathways, autoinducer-2 biosynthesis, and
      menaquinone biosynthesis. The last pathway makes MTAN essential for Helicobacter
      pylori viability. Although structures of various bacterial and plant MTANs have
      been described, the interactions between the homocysteine moiety of SAH and the
      5'-alkylthiol binding site of MTAN have never been resolved. We have determined
      crystal structures of an inactive mutant form of H. pylori MTAN bound to MTA and
      SAH to 1.63 and 1.20 A, respectively. The active form of MTAN was also
      crystallized in the presence of SAH, allowing the determination of the structure
      of a ternary enzyme-product complex resolved at 1.50 A. These structures identify
      interactions between the homocysteine moiety and the 5'-alkylthiol binding site
      of the enzyme. This information can be leveraged for the development of species
      specific MTAN inhibitors that prevent the growth of H. pylori.

PMID- 23148562
TI  - Fluorescence in situ hybridization as adjunct to cytology improves the diagnosis
      and directs estimation of prognosis of malignant pleural effusions.
AB  - BACKGROUND: The identification of malignant cells in effusions by conventional
      cytology is hampered by its limited sensitivity and specificity. The aim of this
      study was to investigate the value of fluorescence in situ hybridization (FISH)
      as adjuncts to conventional cytologic examination in patients with malignant
      pleural effusions. METHODS: We conducted a retrospective cohort study of 93
      inpatients with pleural effusions (72 malignant pleural effusions metastatic from
      11 different organs and 21 benign) over 23 months. All the patients came from
      Chinese northeast areas. Aspirated pleural fluid underwent cytologic examination
      and fluorescence in situ hybridization (FISH) for aneuploidy. We used FISH in
      single-colour or if appropriate in dual-colour evaluation to detect chromosomal
      aberrations (chromosomes 7, 11, and 17) in effusion cells as markers of
      malignancy, to raise the diagnostic yield and identified the efficiency by
      diagnostic biopsy. Predominant cytogenetic anomalies and patterns of intratumor
      cytogenetic heterogeneity were brought in relation to overall survival rate.
      RESULTS: Cytology alone confirmed malignant pleural effusions in 45 of 72
      patients (sensitivity 63%), whereas FISH alone positively identified 48 of 72
      patients (sensitivity 67%). Both tests had high specificity in predicting benign
      effusions. If cytology and FISH were considered together, they exhibited 88%
      sensitivity and 94.5% specificity in discriminating benign and malignant
      effusions. Combined, the two assays were more sensitive than either test alone.
      Although the positive predictive value of each test was 94.5%, the negative
      predictive value of cytology and FISH combined was 78%, better than 47% and 44%
      for FISH and cytology alone, respectively. There was a significantly prolonged
      survival rate for patients with aneuploidy for chromosome 17. CONCLUSIONS: FISH
      in combination with conventional cytology is a highly sensitive and specific
      diagnostic tool for detecting malignant cells in pleural effusions . The high
      sensitivity and specificity may be associated with geographic area and race.
      Simple numeric FISH anomalies may be prognostic.

PMID- 23148564
TI  - De novo cyclic pseudopeptides containing aza-beta3-amino acids exhibiting
      antimicrobial activities.
AB  - De novo cyclic pseudopeptides composed of alpha-amino and aza-beta(3)-amino acids
      were designed with the aim to obtain potential new antimicrobial agents.
      Antimicrobial cyclic pseudopeptides (ACPPs) are based on the properties of
      antimicrobial peptides (AMPs), so they are cationic and amphiphilic. Aza-beta(3)
      amino acids enhance the in vivo half-life of these compounds and offer the
      possibility to incorporate a large variety of side chains. Most of the 13 ACPPs
      exert antimicrobial activities in rich media with broad spectrum of antibacterial
      activities. Selectivity for bacterial over mammalian cells was determined by
      testing the hemolytic activities of ACPPs against sheep red blood cells (sRBC).
      We examined the ratio of cationic to hydrophobic residues as well as the type of
      hydrophobic side chains essential for biological activity of this class of ACPPs.
      These results will be useful for designing potential candidates for a therapeutic
      application.

PMID- 23148565
TI  - Protective effects of N-acetylcysteine on aluminum phosphide-induced oxidative
      stress in acute human poisoning.
AB  - OBJECTIVE: Aluminum phosphide is used as a fumigant. It produces phosphine gas
      (PH3). PH3 is a mitochondrial poison which inhibits cytochrome c oxidase, it
      leads to generation of reactive oxygen species; so one of the most important
      suggested mechanisms for its toxicity is induction of oxidative stress. In this
      regard, it could be proposed that a drug like N-acetylcysteine (NAC) as an
      antioxidant would improve the tolerance of aluminum phosphide-intoxicated cases.
      The objective of this study was to evaluate the protective effects of NAC on
      acute aluminum phosphide poisoning. METHODS: This was a prospective, randomized,
      controlled open-label trial. All patients received the same supportive
      treatments. NAC treatment group also received NAC. The blood thiobarbituric acid
      reactive substances as a marker of lipid peroxidation and total antioxidant
      capacity of plasma were analyzed. RESULTS: Mean ingested dose of aluminum
      phosphide in NAC treatment and control groups was 4.8 +/- 0.9 g vs. 5.4 +/- 3.3
      g, respectively (p = 0.41). Significant increase in plasma malonyldialdehyde
      level in control group was observed (139 +/- 28.2 vs. 149.6 +/- 35.2 MUmol/L, p =
      0.02). NAC infusion in NAC treatment group significantly decreased
      malondialdehyde level (195.7 +/- 67.4 vs. 174.6 +/- 48.9 MUmol/L, p = 0.03),
      duration of hospitalization (2.7 +/- 1.8 days vs. 8.5 +/- 8.2 days, p = 0.02),
      rate of intubation and ventilation (45.4% vs. 73.3%, p = 0.04). Mortality rate in
      NAC treatment and control groups were 36% and 60%, respectively with odds ratio
      2.6 (0.7-10.1, 95% CI). CONCLUSION: NAC may have a therapeutic effect in acute
      aluminum phosphide poisoning.

PMID- 23148566
TI  - Blood leak alarm interference by hydoxocobalamin is hemodialysis machine
      dependent.
AB  - CONTEXT: Hydroxocobalamin has been reported to interfere with the blood leak
      alarm on hemodialysis machines making it difficult to use this treatment modality
      after hydroxocobalamin infusion. OBJECTIVE: The objective was to determine if
      this interference with hydroxocobalamin occurs across hemodialysis machines by
      different manufacturers. Additionally, we aimed to see if this represented a
      colorimetric interference alone or if it is the optical properties of
      hydroxocobalamin. MATERIALS AND METHODS: Hydroxocobalamin was reconstituted per
      package insert. Food coloring was added to 0.9% saline to create the colors of
      the visual spectrum. Optical properties of absorbance and transmittance were
      measured. Hydroxocobalamin and the saline solutions were infused into the
      Fresenius 2008KTM and the Gambro Phoenix X36TM machines. Times were recorded from
      the start of the machine until the solution finished or the alarm triggered.
      RESULTS: When evaluating the Gambro Phoenix X36TM machine and dialysis circuit;
      the alarm did not trigger. In contrast, the blood leak alarm on the Fresenius
      2008KTM machine was tripped by both the red solution and hydoxocobalamin infused
      per the package insert. The alarm stopped the machine between 128 and 132 seconds
      for the red solution and between 30 and 35 seconds with the hydroxocobalamin.
      Membranes of the circuits where the alarm tripped were examined and remained
      intact without blood. Results were validated on different machines with new
      circuits. DISCUSSION: Hydroxocobalamin infusion per package insert and the red
      saline solution prepared with Red Dye 40 both triggered the blood leak alarm and
      stopped the Fresenius 2008KTM machine. However, this was not true for the Gambro
      Phoenix X36TM machine as the alarm never triggered. The interference with the
      Fresenius 2008KTM appears colorimetric due to normal saline with Red Dye 40
      triggering the alarm. CONCLUSION: We alert physicians to become familiar with the
      properties of individual dialysis machines prior to use of hydroxocobalamin. When
      facing difficulties with hemodialysis after the administration of
      hydroxocobalamin, consider attempting with a different manufactures machine or
      model if available or contact the manufacturer directly.

PMID- 23148567
TI  - The role of sexual preferences in intrasexual female competition.
AB  - BACKGROUND: While search costs have long been understood to affect the evolution
      of female preference, other costs associated with mating have been the focus of
      much less attention. Here I consider a novel mate choice cost: female-female
      intrasexual competition, that is, when females compete with each other for mates.
      This competition results in cost to female fecundity, such as a reduction in
      fertility due to decreased direct benefits, sperm limitation, or time and
      resources spent competing for a mate. I asked if female-female competition
      affects the evolution of preferences, and further, if the presence of multiple,
      different, preferences in a population can reduce competitive costs. RESULTS:
      Using population genetic models of preference and trait evolution, I found that
      intrasexual competition leads to direct selection against female preferences, and
      restricts the parameter space under which preference may evolve. I also examined
      how multiple, different, preferences affected preference evolution with female
      intrasexual competition. CONCLUSIONS: Multiple preferences primarily serve to
      increase competitive costs and decrease the range of parameters under which
      preferences may evolve.

PMID- 23148568
TI  - Biocidal activity of metalloacid-coated surfaces against multidrug-resistant
      microorganisms.
AB  - BACKGROUND: The antimicrobial effects of a coating of molybdenum trioxide (MoO3)
      has been recently described. The metalloacid material produces oxonium ions
      (H3O+), which creates an acidic pH that is an effective, non specific
      antimicrobial. We determined the in vitro antimicrobial activity of molybdenum
      trioxide metalloacid-coated surfaces. METHODS: Metalloacid-coated and non-coated
      (control) surfaces were contaminated by exposing them for 15 minutes to microbial
      suspensions containing 105 cfu/mL. Eleven microorganisms responsible for
      nosocomial infections were tested: two Staphylococcus aureus strains (the hetero
      vancomycin intermediate MRSA Mu50 strain and a ST80-PVL-producing MRSA strain); a
      vancomycin-resistant vanA Enterococcus faecium strain; three extended-spectrum
      beta-lactamase-producing Enterobacteriaceae strains; a MBL-producing Pseudomonas
      aeruginosa strain; a multidrug-resistant Acinetobacter baumannii strain; a toxin
      producing Clostridium difficile strain; and two fungi (Candida albicans and
      Aspergillus fumigatus). The assay tested the ability of the coated surfaces to
      kill microorganisms. RESULTS: Against all non-sporulating microorganisms tested,
      metalloacid-coated surfaces exhibited significant antimicrobial activity relative
      to that of the control surfaces within two to six hours after contact with the
      microorganisms (p < 0.001). Microorganism survival on the coated surfaces was
      greatly impaired, whereas microorganism survival on control surfaces remained
      substantial. CONCLUSIONS: We suggest that, facing the continuing shedding of
      microorganisms in the vicinity of colonized or infected patients, the continuous
      biocidal effect of hydroxonium oxides against multidrug-resistant microorganisms
      may help limit environmental contamination between consecutive cleaning
      procedures.

PMID- 23148569
TI  - Association of human mannose receptor in sexual transmission of human
      immunodeficiency virus in serodiscordant couples.
AB  - HIV binds specifically to the human mannose receptor (hMR) on vaginal epithelial
      cells that are devoid of a conventional CD4 receptor. HIV binding to hMR on
      vaginal epithelial cells induces the production of matrix metalloproteinase 9
      (MMP9) leading to degradation of the extracellular matrix, which may increase the
      risk of HIV entry into vaginal epithelial cells and further transmission into
      distal cells. Immunofluorescent localization of hMR on vaginal epithelial cells
      of seronegative females from the general population included the control group
      (n=52) and seronegative females from serodiscordant couples. There was PCR
      amplification of DNA from peripheral blood mononuclear cells (PBMCs) of the
      serodiscordant females for the CCR5 gene flanking the CCR5-Delta32 region; PCR
      amplification and sequencing of the C2-V3 region of HIV variants in PBMCs and
      sperm of the infected male partners of the serodiscordant couples; and the
      presence of hMR on 0-11% of the vaginal epithelial cells of seronegative females
      (n=39) from serodiscordant couples and 90-95% that of a control group of females
      (n=52). Nine of these serodiscordant females did not show a CCR5-Delta32
      deletion. The translated amino acid sequence of the C2-V3 region of the env gene
      of HIV-1C in PBMCs (n=9) and sperm (n=5) of the male partners showed the presence
      of distinct variants and the variation in PBMCs and sperm of serodiscordant males
      was almost similar to that of infected males from concordant couples. The
      presence of hMR in a smaller number of vaginal epithelial cells of serodiscordant
      females prevented binding and HIV entry into these cells and therefore prevented
      sexual transmission of HIV.

PMID- 23148570
TI  - Does the presence of a pharmacist in primary care clinics improve diabetes
      medication adherence?
AB  - BACKGROUND: Although oral hypoglycemic agents (OHAs) are an essential element of
      therapy for the management of type 2 diabetes, OHA adherence is often suboptimal.
      Pharmacists are increasingly being integrated into primary care as part of the
      move towards a patient-centered medical home and may have a positive influence on
      medication use. We examined whether the presence of pharmacists in primary care
      clinics was associated with higher OHA adherence. METHODS: This retrospective
      cohort study analyzed 280,603 diabetes patients in 196 primary care clinics
      within the Veterans Affairs healthcare system. Pharmacists presence, number of
      pharmacist full-time equivalents (FTEs), and the degree to which pharmacy
      services are perceived as a bottleneck in each clinic were obtained from the 2007
      VA Clinical Practice Organizational Survey-Primary Care Director Module. Patient
      level adherence to OHAs using medication possession ratios (MPRs) were
      constructed using refill data from administrative pharmacy databases after
      adjusting for patient characteristics. Clinic-level OHA adherence was measured as
      the proportion of patients with MPR >= 80%. We analyzed associations between
      pharmacy measures and clinic-level adherence using linear regression. RESULTS: We
      found no significant association between pharmacist presence and clinic-level OHA
      adherence. However, adherence was lower in clinics where pharmacy services were
      perceived as a bottleneck. CONCLUSIONS: Pharmacist presence, regardless of the
      amount of FTE, was not associated with OHA medication adherence in primary care
      clinics. The exact role of pharmacists in clinics needs closer examination in
      order to determine how to most effectively use these resources to improve patient
      centered outcomes including medication adherence.

PMID- 23148571
TI  - The discovery of how gender influences age immunological mechanisms in health and
      disease, and the identification of ageing gender-specific biomarkers, could lead
      to specifically tailored treatment and ultimately improve therapeutic success
      rates.
AB  - The control of human health and diseases in the elderly population is becoming a
      challenge, since mean age and life expectation are progressively increasing as
      well as chronic degenerative diseases. These disorders are of complex diagnosis
      and they are difficult to be treated, but it is hoped that the predictive
      medicine will lead to more specific and effective treatment by using specific
      markers to identify persons with high risk of developing disease, before the
      clinical manifestation. Peripheral blood targets and biomarkers are currently the
      most practical, non-invasive means of disease diagnosing, predicting prognosis
      and therapeutic response. Human longevity is directly correlated with the optimal
      functioning of the immune system. Recent findings indicate that the sexual
      dimorphism of T helper (Th) cytokine pathways and the regulation of Th cell
      network homeostasis are normally present in the immune response and undergoes to
      adverse changes with ageing. Furthermore, immune senescence affects both men and
      women, but it does not affect them equally. Therefore, we hypothesize that the
      comprehension of the interferences between these gender specific pathways, the
      ageing immunological mechanism in pathological or healthy state and the current
      therapies, could lead to specifically tailored treatment and eventually improve
      the therapeutic success rates. Reaching this aim requires the identification of
      ageing gender-specific biomarkers that could easily reveal the above mentioned
      correlations.

PMID- 23148572
TI  - From expression pattern to genetic association in asthma and asthma-related
      phenotypes.
AB  - BACKGROUND: Asthma is a complex disease characterized by hyperresponsiveness,
      obstruction and inflammation of the airways. To date, several studies using
      different approaches as candidate genes approach, genome wide association
      studies, linkage analysis and genomic expression leaded to the identification of
      over 300 genes involved in asthma pathophysiology. Combining results from two
      studies of genomic expression, this study aims to perform an association analysis
      between genes differently expressed in bronchial biopsies of asthmatics compared
      to controls and asthma-related phenotypes using the same French-Canadian
      Caucasian population. RESULTS: Before correction, 31 of the 85 genes selected
      were associated with at least one asthma-related phenotype. We found four genes
      that survived the correction for multiple testing. The rs11630178 in aggrecan
      gene (AGC1) is associated with atopy (p=0.0003) and atopic asthma (p=0.0001), the
      rs1247653 in the interferon alpha-inducible protein 6 (IFI6), the rs1119529 in
      adrenergic, alpha-2A-, receptor (ADRA2A) and the rs13103321 in the alcohol
      dehydrogenase 1B (class I), beta polypeptide (ADH1B), are associated with asthma
      (p=0.019; 0.01 and 0.002 respectively). CONCLUSION: To our knowledge, this is the
      first time those genes are associated with asthma and related traits.
      Consequently, our study confirms that genetic and expression studies are
      complementary to identify new candidate genes and to investigate their role to
      improve the comprehension of the complexity of asthma pathophysiology.

PMID- 23148573
TI  - Prospective observational cohort study of Health Related Quality of Life (HRQOL),
      chronic foot problems and their determinants in gout: a research protocol.
AB  - BACKGROUND: Gout is the commonest inflammatory arthritis affecting around 1.4% of
      adults in Europe. It is predominantly managed in primary care and classically
      affects the joints of the foot, particularly the first metatarsophalangeal joint.
      Gout related factors (including disease characteristics and treatment) as well as
      comorbid chronic disease are associated with poor Health Related Quality of Life
      (HRQOL) yet to date there is limited evidence concerning gout in a community
      setting. Existing epidemiological studies are limited by their cross-sectional
      design, selection of secondary care patients with atypical disease and the use of
      generic tools to measure HRQOL. This 3 year primary care-based prospective
      observational cohort study will describe the spectrum of HRQOL in community
      dwelling patients with gout, associated factors, predictors of poor outcome, and
      prevalence and incidence of foot problems in gout patients. METHODS: Adults aged 
      >= 18 years diagnosed with gout or prescribed colchicine or allopurinol in the
      preceding 2 years will be identified through Read codes and mailed a series of
      self-completion postal questionnaires over a 3-year period. Consenting
      participants will have their general practice medical records reviewed.
      DISCUSSION: This is the first prospective cohort study of HRQOL in patients with
      gout in primary care in the UK. The combination of survey data and medical record
      review will allow an in-depth understanding of factors that are associated with
      and lead to poor HRQOL and foot problems in gout. Identification of these factors
      will improve the management of this prevalent, yet under-treated, condition in
      primary care.

PMID- 23148575
TI  - Photocatalytic degradation of methyl orange over nitrogen-fluorine codoped TiO2
      nanobelts prepared by solvothermal synthesis.
AB  - Anatase type nitrogen-fluorine (N-F) codoped TiO(2) nanobelts were prepared by a
      solvothermal method in which amorphous titania microspheres were used as the
      precursors. The as-prepared TiO(2) nanobelts are composed of thin narrow
      nanobelts and it is noted that there are large amount of wormhole-like mesopores
      on these narrow nanobelts. Photocatalytic activity of the N-F codoped TiO(2)
      nanobelts was measured by the reaction of photocatalytic degradation of methyl
      orange. Results indicate that the photocatalytic activity of the N-F codoped
      TiO(2) nanobelts is higher than that of P25, which is mainly ascribed to wormhole
      like mesopores like prison, larger surface area, and enhanced absorption of light
      due to N-F codoping. Interestingly, it is also found that the photocatalytic
      activity can be further enhanced when tested in a new testing method because more
      photons can be captured by the nanobelts to stimulate the formation of the hole
      electron pair.

PMID- 23148576
TI  - Acute portal vein thrombosis precipitated by indomethacin in a HCV-positive
      elderly patient.
AB  - BACKGROUND: An increased risk of venous thromboembolism has been reported in
      patients treated with non-steroidal anti-inflammatory drugs (NSAIDs). We describe
      a case of acute portal vein thrombosis (PVT) in a hepatitis C virus (HCV)
      positive elderly patient following administration of indomethacin. CASE
      PRESENTATION: A 79-year-old HCV-positive man was hospitalized for severe
      abdominal pain, nausea and vomiting, 15 days after starting indomethacin for back
      pain. Clinical signs and imaging evaluations disclosed a picture of PVT.
      Indomethacin was discontinued, and the patient was started on fondaparinux and
      antithrombin. He was discharged 15 days later due to improvement of his clinical
      conditions. Thirty days later, a follow-up ultrasound did not show appreciable
      signs of PVT. The time elapsing between the start of analgesic therapy and PVT
      onset suggests a role of indomethacin as the triggering agent. Indomethacin could
      have precipitated PVT by a combination of at least two detrimental mechanisms: 1)
      direct action on liver vascular endothelium by inhibition of prostacyclin
      biosynthesis; 2) damage to the intestinal mucosa, followed by inflammatory and
      pro-coagulant activation of portal endothelium upon exposure to bacterial
      endotoxins. CONCLUSIONS: This case can be of interest to physicians, who should
      exert caution when prescribing NSAIDs for inflammatory pain in patients with
      background inflammatory dysfunctions of the portal vein endothelium.

PMID- 23148577
TI  - Dynamic magnetic materials based on the cationic coordination polymer
      [Cu(btix)2]n(2n+) [btix = 1,4-bis(triazol-1-ylmethyl)benzene]: tuning the
      structural and magnetic properties through anion exchange.
AB  - A three-dimensional coordination polymer, [Cu(btix)(2)(BF(4))(2)](n) [btix = 1,4
      bis(triazol-1-ylmethyl)benzene], with antiferromagnetic interactions occurring
      via the organic ligand, has been prepared and characterized. It has been shown to
      permit the exchange of anionic species in the crystalline network with
      modification of the magnetic properties. Coordinated BF(4)(-) can be reversibly
      exchanged by different anions with (NO(3)(-) and Cl(-)) or without (PF(6)(-) and
      ClO(4)(-)) dynamic response of the organic ligand, which acts as the only linker
      between the metal centers. Interestingly, an irreversible exchange occurs with
      N(3)(-) anions to generate a new coordination polymer, [Cu(btix)(N(3))(2)](n),
      whose structure has been determined ab initio by powder X-ray diffraction,
      revealing a totally different connectivity between the Cu(II) centers. These
      structural transformations are accompanied by a change of the magnetic
      properties, which have been detected by electron paramagnetic resonance and
      magnetic susceptibility measurements.

PMID- 23148579
TI  - Intracellular release of endocytosed nanoparticles upon a change of ligand
      receptor interaction.
AB  - During passive endocytosis, nanosized particles are initially encapsulated by a
      membrane separating it from the cytosol. Yet, in many applications the
      nanoparticles need to be in direct contact with the cytosol in order to be
      active. We report a simulation study that elucidates the physical mechanisms by
      which such nanoparticles can shed their bilayer coating. We find that
      nanoparticle release can be readily achieved by a pH-induced lowering of the
      attraction between nanoparticle and membrane only if the nanoparticle is either
      very small or nonspherical. Interestingly, we find that in the case of large
      spherical nanoparticles, the reduction of attraction needs to be accompanied by
      exerting an additional tension on the membrane (e.g., via nanoparticle expansion)
      to achieve release. We expect these findings will contribute to the rational
      design of drug delivery strategies via nanoparticles.

PMID- 23148580
TI  - Sites of metastases of anaplastic thyroid carcinoma: autopsy findings in 45 cases
      from a single institution.
AB  - BACKGROUND: Despite surgical treatment, chemotherapy, and/or radiotherapy, the
      vast majority of patients with anaplastic thyroid carcinoma (ATC) have a dismal
      prognosis. Better knowledge of the frequency of metastases to different sites
      might help us to perform the appropriate diagnostic tests before treatment and
      during the course of the disease. The aim of this study was to determine the
      frequency of metastases from ATC in different sites as found at autopsy. METHODS:
      Altogether, 205 patients were treated for ATC at our institute during the years
      1972-2008. Autopsy was performed in 45 cases (30 females, 15 males; median age 66
      years). The relative frequencies of metastases in different sites were analyzed
      using descriptive statistics. RESULTS: Altogether, 41 cases (91%) had metastases
      at autopsy. The most common sites of metastases were the lungs (78%),
      intrathoracic lymph nodes (58%), neck lymph nodes (51%), pleura (29%), adrenal
      glands (24%), liver (20%), brain (18%), heart (18%), and retroperitoneal lymph
      nodes (18%). Less common sites of distant metastases were the pericardium (13%),
      bones (13%), kidneys (13%), mesentery or peritoneum (13%), skin (9%), pancreas
      (4%), stomach (4%), diaphragm (4%), pituitary gland (2%), ovary (2%), jejunum
      (2%), axillary lymph nodes (2%), and gingival mucosa (2%). Both distant and
      regional metastases were present in 23 cases, while only distant metastases were
      present in 18 cases. An extensive local infiltration of the primary tumor was
      found in 76% of the cases. The total number of the involved organs and lymph node
      basins were 123 and 58, respectively. The mean number of metastatic sites was
      4.02+/-2.75. Lung metastases were present in 34 of 38 (89%) of our patients who
      had distant metastases found at autopsy. Of these 34 patients, 27 were known to
      have lung metastases when they were alive. CONCLUSION: Two or more metastatic
      sites were found at autopsy in 84% of cases. The most common metastatic sites are
      lungs, followed by the intrathoracic and neck lymph nodes.

PMID- 23148581
TI  - Increased selectivity toward cytoplasmic versus mitochondrial ribosome confers
      improved efficiency of synthetic aminoglycosides in fixing damaged genes: a
      strategy for treatment of genetic diseases caused by nonsense mutations.
AB  - Compelling evidence is now available that gentamicin and Geneticin (G418) can
      induce the mammalian ribosome to suppress disease-causing nonsense mutations and
      partially restore the expression of functional proteins. However, toxicity and
      relative lack of efficacy at subtoxic doses limit the use of gentamicin for
      suppression therapy. Although G418 exhibits the strongest activity, it is very
      cytotoxic even at low doses. We describe here the first systematic development of
      the novel aminoglycoside (S)-11 exhibiting similar in vitro and ex vivo activity
      to that of G418, while its cell toxicity is significantly lower than those of
      gentamicin and G418. Using a series of biochemical assays, we provide proof of
      principle that antibacterial activity and toxicity of aminoglycosides can be
      dissected from their suppression activity. The data further indicate that the
      increased specificity toward cytoplasmic ribosome correlates with the increased
      activity and that the decreased specificity toward mitochondrial ribosome confers
      the lowered cytotoxicity.

PMID- 23148574
TI  - The 60-day temperature-dependent degradation of midazolam and Lorazepam in the
      prehospital environment.
AB  - BACKGROUND: The choice of the optimal benzodiazepine to treat prehospital status
      epilepticus is unclear. Lorazepam is preferred in the emergency department, but
      concerns about nonrefrigerated storage limits emergency medical services (EMS)
      use. Midazolam is increasingly popular, but its heat stability is undocumented.
      OBJECTIVE: This study evaluated temperature-dependent degradation of lorazepam
      and midazolam after 60 days in the EMS environment. METHODS: Lorazepam or
      midazolam samples were collected prior to (n = 139) or after (n = 229) 60 days of
      EMS deployment during spring-summer months in 14 metropolitan areas across the
      United States. Medications were stored in study boxes that logged temperature
      every minute and were stored in EMS units per local agency policy. Mean kinetic
      temperature (MKT) exposure was derived for each sample. Drug concentrations were
      determined in a central laboratory by high-performance liquid chromatography.
      Concentration as a function of MKT was analyzed by linear regression. RESULTS:
      Prior to deployment, measured concentrations of both benzodiazepines were 1.0
      relative to labeled concentration. After 60 days, midazolam showed no degradation
      (mean relative concentration 1.00, 95% confidence interval [CI] 1.00-1.00) and
      was stable across temperature exposures (adjusted R(2) -0.008). Lorazepam
      experienced little degradation (mean relative concentration 0.99, 95% CI 0.98
      0.99), but degradation was correlated to increasing MKT (adjusted R(2) 0.278).
      The difference between the temperature dependence of degradation of midazolam and
      lorazepam was statistically significant (T = -5.172, p < 0.001). CONCLUSIONS:
      Lorazepam experiences small but statistically significant temperature-dependent
      degradation after 60 days in the EMS environment. Additional study is needed to
      evaluate whether clinically significant deterioration occurs after 60 days.
      Midazolam shows no degradation over this duration, even in high-heat conditions.

PMID- 23148583
TI  - Surgical site infections following transcatheter apical aortic valve
      implantation: incidence and management.
AB  - OBJECTIVE: The present study was undertaken to examine the incidence and
      management of surgical site infection (SSI) in patients submitted to transapical
      transcatheter aortic valve implantation (TA-TAVI). METHODS: From April 2007 to
      December 2011, 154 patients underwent TA-TAVI with an Edwards Sapien
      bioprosthesis (ES) at the Institut Universitaire de Cardiologie et Pneumologie de
      Quebec (IUCPQ) as part of a multidisciplinary program to prospectively evaluate
      percutaneous aortic valve implantation. Patient demographics, perioperative
      variables, and postoperative complications were recorded in a prospective
      registry. RESULTS: Five (3.2%) patients in the cohort presented with an SSI
      during the study period. The infections were all hospital-acquired (HAI) and were
      considered as organ/space SSI's based on Center for Disease Control criteria
      (CDC). Within the first few weeks of the initial procedure, these patients
      presented with an abscess or chronic draining sinus in the left thoracotomy
      incision and were re-operated. The infection spread to the apex of the left
      ventricle in all cases where pledgeted mattress sutures could be seen during
      debridement. Patients received multiple antibiotic regimens without success until
      the wound was surgically debrided and covered with viable tissue. The greater
      omentum was used in three patients and the pectoralis major muscle in the other
      two. None of the patients died or had a recurrent infection. Three of the
      patients were infected with Staphylococcus epidermidis, one with Staphylococcus
      aureus, and one with Enterobacter cloacae. Patients with surgical site infections
      were significantly more obese with higher BMI (31.4+/-3.1 vs 26.2+/-4.4 p=0.0099)
      than the other patients in the cohort. CONCLUSIONS: While TA-TAVI is a minimally
      invasive technique, SSIs, which are associated with obesity, remain a concern.
      Debridement and rib resection followed by wound coverage with the greater omentum
      and/or the pectoralis major muscle were used successfully in these patients.

PMID- 23148584
TI  - Secondary and tertiary sulfonamides: a patent review (2008 - 2012).
AB  - INTRODUCTION: Secondary and tertiary sulfonamides (R-SO(2)NR(1)R(2)) are defined
      by the single or double N-alkyl or N-aryl/heteroaryl substitution of the primary
      sulfonamide respectively. They can be obtained easily by the classical S(N)2 or
      nucleophile acyl substitution displacements using the appropriate synthones. Many
      classes of compounds used in therapy present the substituted sulfonamide groups
      and there is also a continuous interest in different fields such as the
      herbicides herein schematically reported. AREAS COVERED: The intent of this
      article is to give a comprehensive overview of the most important patents in the
      last decade related to pathologies of great interest. All selected patents claim
      new compounds bearing the secondary or/and tertiary sulfonamide moiety, and state
      to have biological activities. The article is neither intended for detailed
      discussions of the sulfonamides mode of action on the specific therapeutic
      targets, nor for their contribution to the physicochemical properties of the
      molecules they are introduced into, as the scientific literature in such topics
      is exhaustive and in many cases, debates are still ongoing. The main fields
      covered are related to pathologies affecting the CNS, cardiac disorders, anti
      virals, inflammation diseases, glaucoma, bone remodeling, anti-cancer, and
      finally a section is also dedicated to herbicides. EXPERT OPINION: The insertion
      of the secondary/tertiary sulfonamide group into the organic scaffolds is
      chemically straightforward and not associated to particular toxicity in the cells
      or in the organisms. Therefore, it is possible to create large libraries of
      compounds, which can be tested for different diseases. As demonstrated by the
      patents reported in the present review, the research in medicinal chemistry, and
      other fields, takes big advantages as new leads are created, and might be further
      developed.

PMID- 23148582
TI  - Genome-derived insights into the biology of the hepatotoxic bloom-forming
      cyanobacterium Anabaena sp. strain 90.
AB  - BACKGROUND: Cyanobacteria can form massive toxic blooms in fresh and brackish
      bodies of water and are frequently responsible for the poisoning of animals and
      pose a health risk for humans. Anabaena is a genus of filamentous diazotrophic
      cyanobacteria commonly implicated as a toxin producer in blooms in aquatic
      ecosystems throughout the world. The biology of bloom-forming cyanobacteria is
      poorly understood at the genome level. RESULTS: Here, we report the complete
      sequence and comprehensive annotation of the bloom-forming Anabaena sp. strain 90
      genome. It comprises two circular chromosomes and three plasmids with a total
      size of 5.3 Mb, encoding a total of 4,738 genes. The genome is replete with
      mobile genetic elements. Detailed manual annotation demonstrated that almost 5%
      of the gene repertoire consists of pseudogenes. A further 5% of the genome is
      dedicated to the synthesis of small peptides that are the products of both
      ribosomal and nonribosomal biosynthetic pathways. Inactivation of the hassallidin
      (an antifungal cyclic peptide) biosynthetic gene cluster through a deletion event
      and a natural mutation of the buoyancy-permitting gvpG gas vesicle gene were
      documented. The genome contains a large number of genes encoding restriction
      modification systems. Two novel excision elements were found in the nifH gene
      that is required for nitrogen fixation. CONCLUSIONS: Genome analysis demonstrated
      that this strain invests heavily in the production of bioactive compounds and
      restriction-modification systems. This well-annotated genome provides a platform
      for future studies on the ecology and biology of these important bloom-forming
      cyanobacteria.

PMID- 23148585
TI  - Structural characterization of the cyclic cystine ladder motif of theta
      defensins.
AB  - The theta-defensins are, to date, the only known ribosomally synthesized cyclic
      peptides in mammals, and they have promising antimicrobial bioactivities. The
      characteristic structural motif of the theta-defensins is the cyclic cystine
      ladder, comprising a cyclic peptide backbone and three parallel disulfide bonds.
      In contrast to the cyclic cystine knot, which characterizes the plant cyclotides,
      the cyclic cystine ladder has not been as well described as a structural motif.
      Here we report the solution structures and nuclear magnetic resonance relaxation
      properties in aqueous solution of three representative theta-defensins from
      different species. Our data suggest that the theta-defensins are more rigid and
      structurally defined than previously thought. In addition, all three theta
      defensins were found to self-associate in aqueous solution in a concentration
      dependent and reversible manner, a property that might have a role in their
      mechanism of action. The structural definition of the theta-defensins and the
      cyclic cystine ladder will help to guide exploitation of these molecules as
      structural frameworks for the design of peptide drugs.

PMID- 23148586
TI  - Bronchial cast hiding a lung cancer.
AB  - A 70-year-old man was admitted for severe hypoxia, haemoptysis and cough. Chest
      X-ray and CT-scan indicated a right-lower-lobe collapse. Bronchoscopy showed its
      occlusion by whitish dense mucus. Aspiration revealed a Bronchial Cast (BC) and a
      stenotic and inflamed orifice of the right-lower-lobe-bronchus which was
      biopsied.Histopathologic examination of BC showed fibrin with lymphocytes and
      neutrophils, and, surprisingly, also the presence of lung cancer. Although the
      association between BC and benign, myxoid-soft-tissue, tracheobronchial tumors
      has been described, the association with lung cancer has not previously been
      reported, and it remains unclear whether it is causal or casual.

PMID- 23148587
TI  - The effect of improved rural sanitation on diarrhoea and helminth infection:
      design of a cluster-randomized trial in Orissa, India.
AB  - BACKGROUND: Infectious diseases associated with poor sanitation such as
      diarrhoea, intestinal worms, trachoma and lymphatic filariasis continue to cause
      a large disease burden in low income settings and contribute substantially to
      child mortality and morbidity. Obtaining health impact data for rural sanitation
      campaigns poses a number of methodological challenges. Here we describe the
      design of a village-level cluster-randomised trial in the state of Orissa, India
      to evaluate the impact of an ongoing rural sanitation campaign conducted under
      the umbrella of India's Total Sanitation Campaign (TSC).We randomised 50 villages
      to the intervention and 50 villages to control. In the intervention villages the
      implementing non-governmental organisations conducted community mobilisation and
      latrine construction with subsidies given to poor families. Control villages
      receive no intervention. Outcome measures include (1) diarrhoea in children under
      5 and in all ages, (2) soil-transmitted helminth infections,  (3) anthropometric
      measures, (4) water quality, (5) number of insect vectors (flies, mosquitoes),
      (6) exposure to faecal pathogens in the environment. In addition we are
      conducting process documentation (latrine construction and use, intervention
      reach), cost and cost-effectiveness analyses, spatial analyses and qualitative
      research on gender and water use for sanitation. RESULTS: Randomisation resulted
      in an acceptable balance between trial arms. The sample size requirements appear
      to be met for the main study outcomes. Delays in intervention roll-out caused
      logistical problems especially for the planning of health outcome follow-up
      surveys. Latrine coverage at the end of the construction period (55%) remained
      below the target of 70%, a result that may, however, be in line with many other
      TSC intervention areas  in India. CONCLUSION: We discuss a number of
      methodological problems encountered thus far in this study that may be typical
      for sanitation trials. Nevertheless, it is expected that the trial procedures
      will allow measuring the effectiveness of a typical rural sanitation campaign,
      with sufficient accuracy and validity.

PMID- 23148588
TI  - Effect of efavirenz, nevirapine, etravirine, and raltegravir administration on
      the pharmacokinetics of ritonavir-boosted darunavir in a population of HIV
      infected patients.
AB  - Abstract   The influence of efavirenz, etravirine, raltegravir, and nevirapine
      administration on the pharmacokinetics of ritonavir-boosted darunavir was
      investigated using population pharmacokinetics analysis. The population was
      composed of 142 patients infected with HIV: darunavir plus nucleoside/nucleotide
      reverse transcriptase inhibitors (NRTI), 54 patients (group A); darunavir plus
      efavirenz+/-NRTI, 4 patients (group B); darunavir plus etravirine+/-NRTI, 5
      patients (group C); darunavir plus nevirapine+/-NRTI, 21 patients (group D);
      darunavir plus raltegravir+/-NRTI, 38 patients (group E); and darunavir plus
      raltegravir and etravirine+/-NRTI, 20 patients (group F). A significant increase
      in darunavir clearance in combination with nevirapine (+66%) and efavirenz
      (+235%) was observed. A significant decrease (p<0.05) in trough plasma
      concentration was observed in groups B and D compared with the other groups. Our
      study indicates that the combination of ritonavir-boosted darunavir and
      etravirine or raltegravir has no significant influence on the pharmacokinetics of
      darunavir in contrast to the combination of ritonavir-boosted darunavir and
      nevirapine or efavirenz, which involves an increase in darunavir clearance and a
      decrease in the plasma concentration of darunavir.

PMID- 23148589
TI  - Epidemiology of low-level bridge jumping in Pittsburgh: a 10-year study.
AB  - BACKGROUND: Outcomes of patients who fall from bridges lower than 160 feet above
      water have been poorly characterized. Pittsburgh offers a unique setting in which
      to study these patients as the city has 41 major bridges, only four of which are
      above 70 feet. OBJECTIVE: This study examined patients who fell or jumped from
      Pittsburgh bridges over a 10-year period for their characteristics, injury
      patterns, and the effects of prehospital care on outcomes. METHODS: We conducted
      a retrospective cohort study of patients who jumped or fell from bridges in
      Pittsburgh, Pennsylvania, over a 10-year period. Subjects were identified through
      manual searches of three data repositories: City of Pittsburgh Bureau of
      Emergency Medical Services (EMS), Pittsburgh River Rescue, and Allegheny County
      Medical Examiner records. Data abstracted included patient name, age, gender,
      date of birth, and address; incident date, time, location, and river conditions;
      prehospital interventions; emergency department intervention; hospital
      disposition; evidence of prior or subsequent psychiatric admission; toxicology
      results or evidence of substance involvement; and causes of death. RESULTS:
      Seventy-four subjects were identified. Most were male (80%) young adults (mean
      age 34.3 years) who lived near the bridges from which they jumped or fell.
      Mortality from bridges less than 50 feet high was 18%; mortality from bridges 180
      feet high was 75%. All patients who required prehospital interventions beyond
      warming or intravenous (IV) fluids died. Injury patterns were similar to those
      described for high-bridge patients, concentrated in the trunk or skull, but low
      bridge injuries were milder and less common. Cause of death was predominantly
      drowning (84%). More than a third (47.3%) of the patients had previous
      psychiatric histories, but evidence of a previous attempt to jump was uncommon
      (5.4%). CONCLUSIONS: People who jump from low- to medium-rise bridges may suffer
      injuries, but most often die from drowning. EMS interventions beyond water rescue
      are typically not helpful, emphasizing the importance of prevention and a water
      rescue plan.

PMID- 23148592
TI  - Transformation of ZnO nanobelts into single-crystalline Mn3O4 nanowires.
AB  - Single-crystalline Mn(3)O(4) nanowires were prepared using the vapor-phase
      transformation of ZnO nanobelts. Mn(3)O(4)-decorated ZnO nanobelts and ZnO
      ZnMn(2)O(4) core-shell nanocables (NCs) were also obtained as reaction
      intermediates. Heteroepitaxial growth of tetragonal spinel Mn(3)O(4) (or
      ZnMn(2)O(4)) on wurtzite ZnO is a possible reason for the growth of single
      crystalline Mn(3)O(4) nanowires. Growth interfaces are possibly formed between
      the wurtzite (101[overline]0)/(21[overline]1[overline]0) and spinel
      (1[overline]01)/(4[overline]11) planes. Various one-dimensional
      homonanostructures and heteronanostructures consisting of n-ZnO, p-Mn(3)O(4), and
      p-ZnMn(2)O(4) can be used to design high-performance gas sensors.

PMID- 23148590
TI  - Defining upper gastrointestinal bleeding from linked primary and secondary care
      data and the effect on occurrence and 28 day mortality.
AB  - BACKGROUND: Primary care records from the UK have frequently been used to
      identify episodes of upper gastrointestinal bleeding in studies of drug toxicity
      because of their comprehensive population coverage and longitudinal recording of
      prescriptions and diagnoses. Recent linkage within England of primary and
      secondary care data has augmented this data but the timing and coding of
      concurrent events, and how the definition of events in linked data effects
      occurrence and 28 day mortality is not known. METHODS: We used the recently
      linked English Hospital Episodes Statistics and General Practice Research
      Database, 1997-2010, to define events by; a specific upper gastrointestinal bleed
      code in either dataset, a specific bleed code in both datasets, or a less
      specific but plausible code from the linked dataset. RESULTS: This approach
      resulted in 81% of secondary care defined bleeds having a corresponding plausible
      code within 2 months in primary care. However only 62% of primary care defined
      bleeds had a corresponding plausible HES admission within 2 months. The more
      restrictive and specific case definitions excluded severe events and almost
      halved the 28 day case fatality when compared to broader and more sensitive
      definitions. CONCLUSIONS: Restrictive definitions of gastrointestinal bleeding in
      linked datasets fail to capture the full heterogeneity in coding possible
      following complex clinical events. Conversely too broad a definition in primary
      care introduces events not severe enough to warrant hospital admission. Ignoring
      these issues may unwittingly introduce selection bias into a study's results.

PMID- 23148591
TI  - Assessing function in patients undergoing joint replacement: a study protocol for
      a cohort study.
AB  - BACKGROUND: Joint replacement is an effective intervention for people with
      advanced arthritis, although there is an important minority of patients who do
      not improve post-operatively. There is a need for robust evidence on outcomes
      after surgery, but there are a number of measures that assess function after
      joint replacement, many of which lack any clear theoretical basis. The World
      Health Organisation has introduced the International Classification of
      Functioning, Disability and Health (ICF), which divides function into three
      separate domains: Impairment, activity limitations and participation
      restrictions. The aim of this study is to compare the properties and
      responsiveness of a selection of commonly used outcome tools that assess
      function, examine how well they relate to the ICF concepts, and to explore the
      changes in the measures over time. METHODS/DESIGN: Two hundred and sixty three
      patients listed for lower limb joint replacement at an elective orthopaedic
      centre have been recruited into this study. Participants attend the hospital for
      a research appointment prior to surgery and then at 3-months and 1-year after
      surgery. At each assessment time, function is assessed using a range of measures.
      Self-report function is assessed using the WOMAC, Aberdeen Impairment, Activity
      Limitation and Participation Restriction Measure, SF-12 and Measure Yourself
      Medical Outcome Profile 2. Clinician-administered measures of function include
      the American Knee Society Score for knee patients and the Harris Hip Score for
      hip patients. Performance tests include the timed 20-metre walk, timed get up and
      go, sit-to-stand-to-sit, step tests and single stance balance test. During the
      performance tests, participants wear an inertial sensor and data from motion
      analysis are collected. Statistical analysis will include exploring the
      relationship between measures describing the same ICF concepts, assessing
      responsiveness, and studying changes in measures over time. DISCUSSION: There are
      a range of tools that can be used to assess function before and after joint
      replacement, with little information about how these various measures compare in
      their properties and responsiveness. This study aims to provide this data on a
      selection of commonly used assessments of function, and explore how they relate
      to the ICF domains.

PMID- 23148594
TI  - Interaction of levitated ionic liquid droplets with water.
AB  - The influence of a humid or dry atmosphere on acoustically levitated ionic liquid
      droplets was studied by volumetric analysis and vibrational spectroscopy.
      Imidazolium-based ionic liquids with two types of anions, fluorinated (BF(4) and
      PF(6)) and alkylsulfate anions, were investigated. The amount of absorbed water
      was correlated with structural differences of the ionic liquids and analyzed in
      terms of equilibrium mole fraction as well as absorption rate. The type of anion
      had the most significant influence on the amount of adsorbed water from the
      atmosphere. Furthermore, spectral changes in the in situ Raman spectra due to
      absorbed water were studied for all investigated ionic liquids. For 1-ethyl-3
      methylimidazolium ethylsulfate, an exemplary detailed analysis of the
      intermolecular interactions between cations, anions and water was carried out
      based on the spectroscopic data. The observed band shifts were explained with a
      hydrogen bond between the anion and water.

PMID- 23148593
TI  - Comments on: Interpretation of genome-wide infinium methylation data from ligated
      DNA in formalin-fixed paraffin-embedded paired tumor and normal tissue.
AB  - BMC Research Notes recently published a research article regarding the use of
      ligated DNA extracted from formalin-fixed paraffin embedded (FFPE) tissue on the
      Illumina Infinium methylation platform - "Interpretation of genome-wide infinium
      methylation data from ligated DNA in formalin-fixed, paraffin-embedded paired
      tumor and normal tissue" Jasmine et al. BMC Research Notes 2012, 5:117. This
      article repeatedly refers to our previous work and concludes that methylation
      data obtained from ligated FFPE extracted DNA should be used with great caution.
      In this Discussion we review the data analysis performed in Jasmine et al's paper
      and suggest limitations which subsequently lead the authors to draw what we
      believe are incorrect conclusions. Moreover, we continue to analyse genome-wide
      methylation data from DNA extracted from FFPE tissue successfully on both the
      HumMeth27 and 450 K arrays.

PMID- 23148595
TI  - Diverse reactions of PhI(OTf)2 with common 2-electron ligands: complex formation,
      oxidation, and oxidative coupling.
AB  - The crystal structures of bis-pyridine stabilized iodine dications
      [PhI(pyr)(2)](2+) are reported as triflate salts, representing the first ligand
      supported iodine dications to be structurally characterized. The pyridine
      complexes are susceptible to ligand exchange in reaction with stronger N-based
      donors such as 4-dimethylaminopyridine. Attempts to extend this reactivity to N
      heterocyclic carbene and phosphine ligands, as has been accomplished in the
      earlier p-block groups, resulted in redox chemistry, with oxidation of the
      ligands rather than coordination.

PMID- 23148596
TI  - What mechanism of niche segregation allows the coexistence of sympatric sibling
      rhinolophid bats?
AB  - INTRODUCTION: Our purpose was to assess how pairs of sibling horseshoe bats
      coexists when their morphology and echolocation are almost identical. We
      collected data on echolocation, wing morphology, diet, and habitat use of
      sympatric Rhinolophus mehelyi and R. euryale. We compared our results with
      literature data collected in allopatry with similar protocols and at the same
      time of the year (breeding season). RESULTS: Echolocation frequencies recorded in
      sympatry for R. mehelyi (mean = 106.8 kHz) and R. euryale (105.1 kHz) were
      similar to those reported in allopatry (R. mehelyi 105-111 kHz; R. euryale 101
      109 kHz). Wing parameters were larger in R. mehelyi than R. euryale for both
      sympatric and allopatric conditions. Moths constitute the bulk of the diet of
      both species in sympatry and allopatry, with minor variation in the amounts of
      other prey. There were no inter-specific differences in the use of foraging
      habitats in allopatry in terms of structural complexity, however we found inter
      specific differences between sympatric populations: R. mehelyi foraged in less
      complex habitats. The subtle inter-specific differences in echolocation frequency
      seems to be unlikely to facilitate dietary niche partitioning; overall
      divergences observed in diet may be explained as a consequence of differential
      prey availability among foraging habitats. Inter-specific differences in the use
      of foraging habitats in sympatry seems to be the main dimension for niche
      partitioning between R. mehelyi and R. euryale, probably due to letter
      differences in wing morphology. CONCLUSIONS: Coexistence between sympatric
      sibling horseshoe bats is likely allowed by a displacement in spatial niche
      dimension, presumably due to the wing morphology of each species, and shifts the
      niche domains that minimise competition. Effective measures for conservation of
      sibling/similar horseshoe bats should guarantee structural diversity of foraging
      habitats.

PMID- 23148597
TI  - The influence of climatic conditions on the transmission dynamics of the 2009
      A/H1N1 influenza pandemic in Chile.
AB  - BACKGROUND: The role of demographic factors, climatic conditions, school cycles,
      and connectivity patterns in shaping the spatio-temporal dynamics of pandemic
      influenza is not clearly understood. Here we analyzed the spatial, age and
      temporal evolution of the 2009 A/H1N1 influenza pandemic in Chile, a southern
      hemisphere country covering a long and narrow strip comprising latitudes 17
      degrees S to 56 degrees S. METHODS: We analyzed the dissemination patterns of the
      2009 A/H1N1 pandemic across 15 regions of Chile based on daily hospitalizations
      for severe acute respiratory disease and laboratory confirmed A/H1N1 influenza
      infection from 01-May to 31-December, 2009. We explored the association between
      timing of pandemic onset and peak pandemic activity and several geographical and
      demographic indicators, school vacations, climatic factors, and international
      passengers. We also estimated the reproduction number (R) based on the growth
      rate of the exponential pandemic phase by date of symptoms onset, estimated using
      maximum likelihood methods. RESULTS: While earlier pandemic onset was associated
      with larger population size, there was no association with connectivity,
      demographic, school or climatic factors. In contrast, there was a latitudinal
      gradient in peak pandemic timing, representing a 16-39-day lag in disease
      activity from the southern regions relative to the northernmost region (P <
      0.001). Geographical differences in latitude of Chilean regions, maximum
      temperature and specific humidity explained 68.5% of the variability in peak
      timing (P = 0.01). In addition, there was a decreasing gradient in reproduction
      number from south to north Chile (P < 0.0001). The regional mean R estimates were
      1.6-2.0, 1.3-1.5, and 1.2-1.3 for southern, central and northern regions,
      respectively, which were not affected by the winter vacation period. CONCLUSIONS:
      There was a lag in the period of most intense 2009 pandemic influenza activity
      following a South to North traveling pattern across regions of Chile,
      significantly associated with geographical differences in minimum temperature and
      specific humidity. The latitudinal gradient in timing of pandemic activity was
      accompanied by a gradient in reproduction number (P < 0.0001). Intensified
      surveillance strategies in colder and drier southern regions could lead to
      earlier detection of pandemic influenza viruses and improved control outcomes.

PMID- 23148598
TI  - Phenyltetrahydroisoquinoline-pyridinaldoxime conjugates as efficient uncharged
      reactivators for the dephosphylation of inhibited human acetylcholinesterase.
AB  - Pyridinium and bis-pyridinium aldoximes are used as antidotes to reactivate
      acetylcholinesterase (AChE) inhibited by organophosphorus nerve agents. Herein,
      we described a series of nine nonquaternary phenyltetrahydroisoquinoline
      pyridinaldoxime conjugates more efficient than or as efficient as pyridinium
      oximes to reactivate VX-, tabun- and ethyl paraoxon-inhibited human AChE. This
      study explores the structure-activity relationships of this new family of
      reactivators and shows that 1b-d are uncharged hAChE reactivators with a broad
      spectrum.

PMID- 23148600
TI  - Sleep and organizational citizenship behavior: the mediating role of job
      satisfaction.
AB  - We examine sleep as an important factor beyond the work domain that is relevant
      to organizational citizenship behavior. In a field study of 87 employees from a
      variety of organizations, an objective measure of sleep quantity predicted
      organizational citizenship behavior directed toward organizations but not
      organizational citizenship behavior directed toward individuals. Additionally,
      job satisfaction mediated this relationship. In a second field study of 85
      working college students, we found that natural variation in daily sleep over the
      course of a work week predicted daily variance in organizational citizenship
      behavior directed toward both individuals and organizations, and that job
      satisfaction mediated these relationships. Based on these findings, we discuss
      theoretical and practical implications of sleep-deprived employees.

PMID- 23148599
TI  - Anopheles salivary gland proteomes from major malaria vectors.
AB  - BACKGROUND: Antibody responses against Anopheles salivary proteins can indicate
      individual exposure to bites of malaria vectors. The extent to which these
      salivary proteins are species-specific is not entirely resolved. Thus, a better
      knowledge of the diversity among salivary protein repertoires from various
      malaria vector species is necessary to select relevant genus-, subgenus- and/or
      species-specific salivary antigens. Such antigens could be used for quantitative
      (mosquito density) and qualitative (mosquito species) immunological evaluation of
      malaria vectors/host contact. In this study, salivary gland protein repertoires
      (sialomes) from several Anopheles species were compared using in silico analysis
      and proteomics. The antigenic diversity of salivary gland proteins among
      different Anopheles species was also examined. RESULTS: In silico analysis of
      secreted salivary gland protein sequences retrieved from an NCBInr database of
      six Anopheles species belonging to the Cellia subgenus (An. gambiae, An.
      arabiensis, An. stephensi and An. funestus) and Nyssorhynchus subgenus (An.
      albimanus and An. darlingi) displayed a higher degree of similarity compared to
      salivary proteins from closely related Anopheles species. Additionally,
      computational hierarchical clustering allowed identification of genus-, subgenus-
      and species-specific salivary proteins. Proteomic and immunoblot analyses
      performed on salivary gland extracts from four Anopheles species (An. gambiae,
      An. arabiensis, An. stephensi and An. albimanus) indicated that heterogeneity of
      the salivary proteome and antigenic proteins was lower among closely related
      anopheline species and increased with phylogenetic distance. CONCLUSION: This is
      the first report on the diversity of the salivary protein repertoire among
      species from the Anopheles genus at the protein level. This work demonstrates
      that a molecular diversity is exhibited among salivary proteins from closely
      related species despite their common pharmacological activities. The involvement
      of these proteins as antigenic candidates for genus-, subgenus- or species
      specific immunological evaluation of individual exposure to Anopheles bites is
      discussed.

PMID- 23148602
TI  - Improved access and visibility during stapling of the ultra-low rectum: a
      comparative human cadaver study between two curved staplers.
AB  - BACKGROUND: The purpose of this study was to compare in human cadavers the
      applicability of a commonly used stapling device, the CONTOUR(r) curved cutter
      (CC) (Ethicon Endo-Surgery, Cincinnati, OH) to a newly released, curved stapler,
      the Endo GIATM Radial Reload with Tri-StapleTM Technology (RR) (Covidien, New
      Haven, CT) METHODS: Four experienced surgeons performed deep pelvic dissection
      with total mesorectal excision (TME) of the rectum in twelve randomized male
      cadavers. Both stapling devices were applied to the ultra-low rectum in coronal
      and sagittal configurations. Extensive measurements were recorded of anatomic
      landmarks for each cadaver pelvis along with various aspects of access,
      visibility, and ease of placement for each device. RESULTS: The RR reached
      significantly lower into the pelvis in both the coronal and sagittal positions
      compared to the CC. The median distance from the pelvic floor was 1.0 cm compared
      to 2.0 cm in the coronal position, and 1.0 cm versus 3.3 cm placed sagitally, p <
      0.0001. Surgeons gave a higher visibility rating with less visual impediment in
      the sagittal plane using the RR Stapler. Impediment of visibility occurred in
      only 10% (5/48) of RR applications in the coronal position, compared to a rate of
      48% (23/48) using the CC, p = 0.0002. CONCLUSIONS: The RR device performed
      significantly better when compared to the CC stapler in regards to placing the
      stapler further into the deep pelvis and closer to the pelvic floor, while
      causing less obstructing of visualization.

PMID- 23148601
TI  - Structural insights into the mechanism of four-coordinate Cob(II)alamin formation
      in the active site of the Salmonella enterica ATP:Co(I)rrinoid
      adenosyltransferase enzyme: critical role of residues Phe91 and Trp93.
AB  - ATP:co(I)rrinoid adenosyltransferases (ACATs) are enzymes that catalyze the
      formation of adenosylcobalamin (AdoCbl, coenzyme B(12)) from cobalamin and ATP.
      There are three families of ACATs, namely, CobA, EutT, and PduO. In Salmonella
      enterica, CobA is the housekeeping enzyme that is required for de novo AdoCbl
      synthesis and for salvaging incomplete precursors and cobalamin from the
      environment. Here, we report the crystal structure of CobA in complex with ATP,
      four-coordinate cobalamin, and five-coordinate cobalamin. This provides the first
      crystallographic evidence of the existence of cob(II)alamin in the active site of
      CobA. The structure suggests a mechanism in which the enzyme adopts a closed
      conformation and two residues, Phe91 and Trp93, displace 5,6
      dimethylbenzimidazole, the lower nucleotide ligand base of cobalamin, to generate
      a transient four-coordinate cobalamin, which is critical in the formation of the
      AdoCbl Co-C bond. In vivo and in vitro mutational analyses of Phe91 and Trp93
      emphasize the important role of bulky hydrophobic side chains in the active site.
      The proposed manner in which CobA increases the redox potential of the
      cob(II)alamin/cob(I)alamin couple to facilitate formation of the Co-C bond
      appears to be analogous to that utilized by the PduO-type ACATs, where in both
      cases the polar coordination of the lower ligand to the cobalt ion is eliminated
      by placing that face of the corrin ring adjacent to a cluster of bulky
      hydrophobic side chains.

PMID- 23148603
TI  - On the origin of free and bound staling aldehydes in beer.
AB  - The chemistry of beer flavor instability remains shrouded in mystery, despite
      decades of extensive research. It is, however, certain that aldehydes play a
      crucial role because their concentration increase coincides with the appearance
      and intensity of "aged flavors". Several pathways give rise to a variety of key
      flavor-active aldehydes during beer production, but it remains unclear as to what
      extent they develop after bottling. There are indications that aldehydes, formed
      during beer production, are bound to other compounds, obscuring them from
      instrumental and sensory detection. Because freshly bottled beer is not in
      chemical equilibrium, these bound aldehydes might be released over time, causing
      stale flavor. This review discusses beer aging and the role of aldehydes,
      focusing on both sensory and chemical aspects. Several aldehyde formation
      pathways are taken into account, as well as aldehyde binding in and release from
      imine and bisulfite adducts.

PMID- 23148604
TI  - Metalloporphyrin Co(III)TMPyP ameliorates acute, sublethal cyanide toxicity in
      mice.
AB  - The formation of Co(III)TMPyP(CN)(2) at pH 7.4 has been shown to be completely
      cooperative (alpha(H) = 2) with an association constant of 2.1 (+/-0.2) * 10(11).
      The kinetics were investigated by stopped-flow spectrophotometry and revealed a
      complicated net reaction exhibiting 4 phases at pH 7.4 under conditions where
      cyanide was in excess. The data suggest molecular HCN (rather than CN(-)) to be
      the attacking nucleophile around neutrality. The two slower phases do not seem to
      be present when cyanide is not in excess, and the other two phases have rates
      comparable to that observed for cobalamin, a known effective cyanide scavenger.
      Addition of bovine serum albumin (BSA) did not affect the cooperativity of
      cyanide binding to Co(III)TMPyP, only lowered the equilibrium constant slightly
      to 1.2 (+/-0.2) * 10(11) and had an insignificant effect on the observed rate. A
      sublethal mouse model was used to assess the effectiveness of Co(III)TMPyP as a
      potential cyanide antidote. The administration of Co(III)TMPyP to sodium cyanide
      intoxicated mice resulted in the time required for the surviving mice to right
      themselves from a supine position being significantly decreased (9 +/- 2 min)
      compared to that of the controls (33 +/- 2 min). All observations were consistent
      with the demonstrated antidotal activity of Co(III)TMPyP operating through a
      cyanide-binding (i.e., scavenging) mechanism.

PMID- 23148605
TI  - An insight on career satisfaction level, mental distress and gender differences
      in working conditions among Japanese obstetricians and gynecologists.

PMID- 23148606
TI  - Effects of long-term occlusal hypofunction and its recovery on the morphogenesis
      of molar roots and the periodontium in rats.
AB  - OBJECTIVES: To investigate the effects of long-term, artificially created,
      hypofunctional occlusion and its recovery on the morphology of rat molar roots.
      MATERIAL AND METHODS: Eighteen 5-week-old Wistar-strain male rats were randomly
      divided according to their periodontal conditions into normal, hypofunctional,
      and recovery groups (n = 6 in each). In the experimental hypofunctional and
      recovery groups, a bite-raising appliance was set to produce hypofunction at the
      molar region. All groups were analyzed at 16 weeks of age using three-dimensional
      micro-computed tomography. Root length, width, and area as well as the thickness
      and the area of the periodontal ligament (PDL) space of the maxillary first molar
      were calculated. RESULTS: Roots were longer and narrower in the hypofunctional
      group than in the control group. The mesial root in particular showed a dramatic
      change. Root area also decreased significantly in the hypofunctional group
      compared to the other groups. Moreover, the PDL thickness and area decreased
      significantly in the hypofunctional group compared to the control group, but
      increased in the recovery group compared to the hypofunctional group.
      CONCLUSIONS: These findings suggest that root size and PDL structure may be
      reduced due to disuse atrophy resulting from a defect in occlusal function, but
      may be recovered following a gain of occlusal stimuli.

PMID- 23148607
TI  - Maxillary growth and maturation during infancy and early childhood.
AB  - OBJECTIVE: To describe maxillary growth and maturation during infancy and early
      childhood. MATERIALS AND METHODS: Serial cephalograms (N=210) of 30 subjects (15
      females and 15 males) from the Bolton-Brush Growth Study were analyzed. Each
      subject had a series of six consecutive cephalograms taken between birth and 5
      years of age, as well as one adult cephalogram. Twelve maxillary measurements
      (eight linear and four angular) and seven landmarks were used to characterize
      maxillary growth. Maturation of the linear measures was described as a percentage
      of adult status. RESULTS: Maxillary and anterior cranial base size increased in
      both sexes between 0.4 and 5 years of age. The linear anteroposterior (AP)
      measures (S-SE, SE-N, ANS-PNS) increased almost as much as the vertical measures
      (S-PNS, SE-PNS, N-A, N-ANS) over the first 5 years. After 5 years of age there
      was significantly more vertical than AP growth. The size and shape changes that
      occurred were greatest between 0.4 and 1 years; yearly velocities decelerated
      regularly thereafter. Overall linear growth changes that occurred between 0.5 and
      5 years of age (a span of 4.5 years) were generally greater than the changes in
      maxillary growth that occurred between 5 and 16 years (a span of 11 years). The
      linear measures showed a gradient of maturation, with the AP measures being more
      mature than the vertical measures. Male maxillae were less mature than female
      maxillae at every age. CONCLUSIONS: The maxilla undergoes its greatest postnatal
      growth change during infancy and early childhood, when relative AP growth and
      maturation are emphasized.

PMID- 23148609
TI  - Novel Wnt signaling and other pathway inhibitors in the colorectal cancer genomic
      landscape era.

PMID- 23148608
TI  - Comparison of the anti-inflammatory effects of Cilomilast, Budesonide and a p38
      Mitogen activated protein kinase inhibitor in COPD lung tissue macrophages.
AB  - Chronic Obstructive Pulmonary Disease (COPD) is a disease characterized by a
      largely irreversible airflow obstruction and a persistent, excessive inflammatory
      response. Alveolar macrophages (AMs) are increased in the lungs of COPD patients,
      and act as orchestrators of the inflammatory response, releasing a range of
      mediators to coordinate recruitment and activation of leukocytes. Attempts to
      treat the inflammatory component of COPD with anti-inflammatory drugs such as
      steroids has met with limited success. In this study, we compared the ability of
      the phosphodiesterase IV (PDEIV) inhibitor Cilomilast, the steroid Budesonide,
      and the p38 mitogen activated protein kinase inhibitor BIRB-796 to inhibit tumour
      necrosis factor alpha (TNFalpha) and interleukin 6 (IL-6) releases from AMs
      isolated from COPD lung transplant tissue. All studies were carried out with
      appropriate ethical approval and written, informed consent was obtained from each
      subject. Cilomilast had little effect on cytokine release from AMs. There was
      considerable variability in the responsiveness of AMs to Budesonide, with a
      subset of AMs responding poorly to Budesonide. BIRB-796 inhibited TNFalpha
      release from all AM donors, including those that responded poorly to steroids.
      Treatment with BIRB-796 and Budesonide together gave an additive decrease in TNFa
      release. These results suggest that a p38 inhibitor may provide advantages over
      existing anti-inflammatory treatments for COPD, either as an add-on to existing
      therapy, or to treat patients who respond poorly to steroids.

PMID- 23148611
TI  - Interview with Johann de Bono for Future Oncology. Interviewed by Francesca Lake.
AB  - Johann de Bono speaks to Francesca Lake, Commissioning Editor. Johann de Bono
      leads the prostate cancer team at the Institute of Cancer Research (London, UK).
      He completed his PhD at the Beatson Institute of Cancer Research (Glasgow, UK)
      and was awarded a scholarship in 2000 that allowed him to undergo research on
      statistical issues in clinical trials for targeted drugs at the Cancer Research
      and Biostatistics SWOG Headquarters, a National Cancer Institute-supported
      organization at the Fred Hutchinson Cancer Center (WA, USA). He then spent 3
      years working in the Institute of Drug Development in San Antonio (TX, USA), and
      then joined The Institute of Cancer Research and The Royal Marsden NHS Foundation
      trust in 2003. He has since been involved in developing over 100 new drugs, some
      of which are currently available to patients. One of these drugs is enzalutamide,
      which has recently been submitted for European marketing authorization following
      positive clinical trials.

PMID- 23148612
TI  - Everolimus and its role in hormone-resistant and trastuzumab-resistant metastatic
      breast cancer.
AB  - Advances in targeted therapies have improved progression-free and overall
      survival in women with metastatic breast cancer; however, regardless of efficacy,
      resistance almost always occurs eventually. Upregulation of the PI3K/AKT/mTOR
      pathway, which promotes cell growth and proliferation, is a means of escaping
      responsiveness to hormone therapy in hormone receptor-positive disease, or
      trastuzumab in HER2-positive disease. Everolimus, an inhibitor of mTOR, has shown
      promise in early clinical trials in metastatic breast cancer and is currently
      being studied in larger Phase II and III clinical trials, combined with hormone
      therapy or trastuzumab with or without cytotoxic chemotherapy. In this article,
      we discuss the mechanistic and preclinical data for everolimus, efficacy and
      safety results of clinical trials, and the landscape looking forward.

PMID- 23148613
TI  - RTK inhibition: looking for the right pathways toward a miracle.
AB  - Evaluation of: Lu KV, Chang JP, Parachoniak CA et al. VEGF inhibits tumor cell
      invasion and mesenchymal transition through a MET/VEGFR2 complex. Cancer Cell
      22(1), 21-35 (2012). In glioblastoma, a well-characterized angiogenic target is
      VEGF. Bevacizumab is a humanized monoclonal antibody that binds to VEGF and was
      developed to inhibit the VEGF signaling pathway. Based on promising results from
      clinical trials that bevacizumab can prolong progression-free survival in
      recurrent glioblastoma patients, the US FDA granted this drug accelerated
      approval for the treatment of recurrent or progressive glioblastoma; however,
      there has been no evidence that the overall median survival of patients is
      prolonged. More recently, Phase II clinical trials tested bevacizumab in
      combination with traditional radiation and/or temozolamide in newly diagnosed
      glioblastoma patients and again showed prolonged progression-free survival in
      these patients, but overall survival was not significantly changed. More
      importantly, there was evidence that tumors resistant to or recurring after
      bevacizumab treatment often showed a more aggressive phenotype. Due to the lack
      of effective post-bevacizumab therapies, it has been suggested that treatment
      with bevacizumab not be used until patients have developed late-stage recurrent
      tumors. Under these circumstances, there is a timely need to uncover the
      mechanisms of resistance to bevacizumab. In this article, Lu et al. reported a
      novel mechanism whereby VEGF negatively regulates tumor cell invasion by blocking
      MET phosphorylation in the MET/VEGFR2 complex. They showed that inhibiting the
      VEGF pathway results in MET activation in VEGF-knockout mouse models and in
      patients after bevacuzimub treatment, and that MET knockdown blocked the
      invasiveness of VEGF knockout tumors, suggesting that blocking the MET pathway
      can prevent post-bevacizumab treatment tumor recurrence, providing a strong
      rationale for using a combination of MET and VEGF receptor inhibitors to treat
      glioblastoma patients.

PMID- 23148614
TI  - Personalized therapy for metastatic melanoma: could timing be everything?
AB  - There is ample evidence that immune-related processes in humans are under
      temporal regulation. The circadian variation of humoral and cellular immunity is
      well documented and appears to be hormonally modulated via the hypothalamic
      pituitary-adrenal axis. In advanced melanoma, it has recently been demonstrated
      that systemic immunity is repolarized toward a global state of chronic
      inflammation (Th2 dominance) and appears to be governed by infradian biorhythms
      of cytokines and immune cell subsets, which extend beyond the 24-h circadian
      variability reported in healthy volunteers. It is suggested that synchronizing
      administration of lymphodepleting chemotherapy (temozolomide) with these
      endogenous (individualized) immune dynamics (biorhythms) in patients with
      advanced/metastatic melanoma improves clinical outcomes compared with
      temozolomide used in a conventional 'random delivery' fashion.

PMID- 23148616
TI  - Pro-metastatic tumor-stroma interactions in breast cancer.
AB  - The vast majority of breast cancer-related deaths are due to metastatic disease.
      Reciprocal and complex interactions between epithelial tumor cells and the
      various components of the tumor microenvironment influence tumor progression and
      metastases although the molecular mechanisms underlying these metastasis
      promoting effects are not fully characterized. Identifying and understanding
      pathways of tumor-stroma cross-talk are likely to lead to the development of
      novel prognostic biomarkers for metastasis and strategies to prevent metastasis
      at its earliest stages, resulting in improved patient outcomes.

PMID- 23148615
TI  - Epigenetic mechanisms in oral carcinogenesis.
AB  - Dysregulation of gene expression is a frequent occurrence in oral squamous cell
      carcinoma (OSCC). However, accumulating evidence suggests that in contrast to
      genetics, epigenetic modifications consisting of aberrant DNA methylation,
      histone modifications and altered expression of miRNAs induce OSCC tumorigenesis
      and perhaps play a more central role in the evolution and progression of this
      disease. The unifying theme among these three epigenetic mechanisms remains the
      same, which is aberrant regulation of gene expression. In this article, we
      provide a comprehensive review of the impact of epigenetics on oral tumorigenesis
      with a systematic report on aberrant DNA methylation, histone modifications and
      miRNA regulation in the pathogenesis of OSCC. We provide insights into recent
      studies on the prospect of biomarkers for early detection and indication of
      disease recurrence, and novel treatment modalities.

PMID- 23148617
TI  - Clinical imaging of tumor angiogenesis.
AB  - Angiogenesis is an integral part of tumor growth and invasion. This has led to
      the emergence of several antiangiogenic therapies and stimulated efforts to
      accurately evaluate the extent of angiogenesis before and in response to
      anticancer treatment. The most commonly used approach has been the assessment of
      new vessel formation in histological samples. However, it is becoming apparent
      that this is insufficient for a full understanding of tumor physiology and for in
      vivo guidance of cancer management. Imaging has the potential to provide
      noninvasive and repeatable assessment of the angiogenic process. Imaging
      approaches use a variety of modalities and are aimed at either assessment of the
      functional integrity of tumor vasculature or assessment of its molecular status.
      This review summarizes the aims and methods of clinical tumor angiogenesis
      imaging, including present technologies and ones that will be developed within
      the next 5-10 years.

PMID- 23148618
TI  - Targeting neddylation in cancer therapy.
AB  - The neddylation conjugation pathway has a pivotal role in mediating
      ubiquitination of proteins and regulation of numerous biological processes.
      Dysregulation in the ubiquitination and neddylation pathways is associated with
      many cancers. Ubiquitination involves covalent attachment of ubiquitin to target
      proteins, leading to protein degradation by the proteasome system. The activity
      of the E3-ubiquitin ligase family, cullin-RING ligases, is essential for
      promoting ubiquitin transfer to the appropriate substrates. Neddylation, a
      process mediated by the protein NEDD8, is required for conformational changes of
      cullins, a scaffolding protein situated in the core of cullin-RING ligases, and
      regulation of E3 ligase activity. In this review, we present a comprehensive
      discussion of the recent findings on the neddylation pathway and its importance
      during tumorigenesis. The ramifications regarding the potential therapeutic use
      of ubiquination and neddylation inhibition are also discussed.

PMID- 23148619
TI  - Polymer nanoparticulate drug delivery and combination cancer therapy.
AB  - This review describes the scientific background, current achievement and future
      perspective of combination therapy using polymer nanoparticle drug carriers in
      cancer treatment. Nanotechnology-based drug delivery is expected to dramatically
      change combination cancer therapy by controlling accumulation and distribution
      patterns of multiple drugs selectively in disease sites. Rationally designed
      polymer materials can produce functional nanoparticulate drug carriers that can
      be used in various biomedical applications. In comparison with conventional drug
      combination approaches, using polymer nanoparticle drug carriers appears to
      suppress tumor growth more efficiently, potentially overcoming multidrug
      resistance in many cancers. It also provides versatile combination options for a
      variety of therapeutic agents, molecular targeting agents and nucleotide drugs.

PMID- 23148620
TI  - Management of gastrointestinal mucositis due to cancer therapies in pediatric
      patients: results of a case series with SAMITAL((r)).
AB  - BACKGROUND: Gastrointestinal mucositis is a common debilitating complication of
      chemotherapy and one for which there is currently no effective long-term
      treatment. OBJECTIVES: To report our experience with the use of SAMITAL((r)), a
      new oral suspension formulation based on the combination of three standardized
      extracts from Vaccinium myrtillus, Macleaya cordata fruits and Echinacea
      angustifolia roots in the prevention and treatment of chemotherapy-induced
      gastrointestinal mucositis in pediatric patients. METHODS: 20 pediatric patients
      undergoing chemotherapy for a range of oncological conditions were followed.
      Patients initially received oral SAMITAL((r)) to treat gastrointestinal mucositis
      and were then given SAMITAL((r)) prophylactically to prevent recurrences with
      successive cycles of chemotherapy. RESULTS: SAMITAL((r)) significantly decreased
      gastrointestinal mucositis grade after the first episode with a reduction of mean
      scores from 3.2 +/- 0.7 at baseline to 0.4 +/- 0.6 at the end of treatment (p <
      0.001). SAMITAL((r)) reduced pain, mucosal erosions, bleeding and
      dysphagia/feeding impairment. SAMITAL((r)) improved patients' overall condition
      and quality of life after the first administration and lowered the need for
      parenteral nutrition. Importantly, it allowed chemotherapy cycles to be continued
      without complications. CONCLUSION: Results from this case series suggest that
      SAMITAL((r)) may play an important role in the prevention and treatment of
      chemotherapy-induced gastrointestinal mucositis in children and adolescents and
      as such warrants investigation in controlled studies.

PMID- 23148621
TI  - Germ cell cancer presenting as gastrointestinal bleeding and developing brain
      metastases: case report and review of the literature.
AB  - This paper describes a rare case of germ cell cancer with duodenum, brain and
      lung metastases. The patient presented with melena and left testicle enlargement.
      Orchiectomy revealed mixed germ cell cancer, enteroscopy revealed duodenal
      choriocarcinoma, and chest x-ray and computed tomography (CT) showed bilateral
      lung metastases. The patient received and tolerated cisplatinum-based
      chemotherapy, and responded well. However, he developed seizures 3 months later.
      MRI showed brain metastases and he was treated with whole-brain radiation. One
      month later, he developed progressive dyspnea. Chest CT showed worsening lung
      metastases. He received second-line chemotherapy, but died due to multiorgan
      failure. Germ cell cancer with nonpulmonary metastases has poor prognosis and the
      management of these patients requires a multimodal approach. Head CT should be
      considered as routine screening for all germ cell cancer patients on initial
      diagnosis and brain MRI should be considered for high-risk patients (with an
      embryo- or choriocarcinoma histology, dramatically elevated beta-human chorionic
      gonadotropin and lung involvement).

PMID- 23148622
TI  - Cytologically confirmed splenic metastases in breast cancer.
AB  - Relatively few cases of splenic metastases have been reported in the literature.
      Metastases to the spleen generally occur in the context of multivisceral
      involvement during the late stage of disease, while isolated splenic metastases
      are far less frequent. The primary cancer types commonly leading to splenic
      metastases are skin melanoma and gynecologic, colorectal and gastric cancers.
      Breast cancer is considered a rare source of splenic metastases, with few cases
      being reported in the literature. As a contribution to the literature, we report
      here on a case of splenic metastasis in a patient with breast cancer treated at
      the Department of Medical Oncology at our institution (Bellaria-Maggiore
      Hospital, Azienda USL of Bologna, Italy).

PMID- 23148624
TI  - Rotational rehybridization and the high temperature phase of UC2.
AB  - The screened hybrid approximation (HSE) of density functional theory (DFT) is
      used to examine the structural, optical, and electronic properties of the high
      temperature phase, cubic UC(2). This phase contains C(2) units with a computed C
      C distance of 1.443 A which is in the range of a CC double bond; U is formally
      4+, C(2) 4-. The closed shell paramagnetic state (NM) was found to lie lowest.
      Cubic UC(2) is found to be a semiconductor with a narrow gap, 0.4 eV.
      Interestingly, the C(2) units connecting two uranium sites can rotate freely up
      to an angle of 30 degrees , indicating a hindered rotational solid. Ab-initio
      molecular dynamic simulations (HSE) show that the rotation of C(2) units in the
      low temperature phase (tetragonal UC(2)) occurs above 2000 K, in good agreement
      with experiment. The computed energy barrier for the phase transition from
      tetragonal UC(2) to cubic UC(2) is around 1.30 eV per UC(2). What is fascinating
      about this system is that at high temperature, the phase transformation to the
      cubic phase is associated with a rehybridization of the C atoms from sp to sp(3).

PMID- 23148625
TI  - Activated leukocyte cell adhesion molecule is a marker for thyroid carcinoma
      aggressiveness and disease-free survival.
AB  - BACKGROUND: Currently, there are no protein biomarkers for aggressive subtypes of
      thyroid carcinomas (TC) in clinical use that would allow for early detection and
      patient management. We hypothesized that activated leukocyte cell adhesion
      molecule (ALCAM or CD166) expression in thyroid tissues will reveal ALCAM to be a
      potential diagnostic and/or prognostic marker for TC aggressiveness. METHODS:
      Forty-five benign and 158 malignant thyroid tissues were analyzed for ALCAM
      expression using immunohistochemistry. ALCAM expression was correlated with
      different subtypes and clinicopathological features of TC, as well as patient
      disease-free survival. RESULTS: Combined membranous and cytoplasmic (total)
      expression of ALCAM was significantly reduced in patients with
      poorly/undifferentiated (aggressive) TC as compared to well-differentiated
      (nonaggressive) tumors (p<0.001; area-under-curve=0.865, sensitivity=82%,
      specificity=74%). The decreased ALCAM expression in TC correlated significantly
      with extrathyroidal extension, distant metastasis, and TC histotype. Notably,
      Kaplan-Meier survival analysis for follow-up data of 134 patients revealed
      significantly reduced disease-free survival for patients with TC with decreased
      ALCAM membranous, cytoplasmic, and total expression. Median survival of patients
      with decreased cytoplasmic ALCAM expression was 6 years, as compared to 13.7
      years for patients with higher ALCAM expression (p<0.001). CONCLUSION: ALCAM has
      the potential to serve as a diagnostic and prognostic biomarker for aggressive
      TC. This protein can be taken forward for analysis in sera of patients with TC to
      determine its applicability as a minimally invasive serum biomarker for TC
      aggressiveness and patient disease-free survival.

PMID- 23148626
TI  - The growth and composition of primary and community-based care services. Metrics
      and evidence from the Italian National Health Service.
AB  - BACKGROUND: Over the past few decades, in OECD countries there has been a general
      growing trend in the prevalence of out-of-hospital healthcare services, but there
      is a general lack of data on the use of these services. METHODS: We defined a
      list of 303 indicators related to primary and community healthcare services in
      collaboration with 13 Italian Local Health Authorities (LHAs). Then, for each
      LHA, we collected and analyzed these indicators for two different years (2003 and
      2007). RESULTS: Out-of-hospital care absorbs 56% of all costs in our sample of
      LHAs. Expenditure on outpatients' visits to specialists and on diagnostic
      examinations accounts for 13% of the costs, while spending on primary care
      (including prevention and public health) accounts for 9%, and for intermediate
      structures (including those related to rehabilitation, elderly people, disabled
      people, and mental health) the figure is 11%. Different Italian LHAs have made
      different strategic choices with respect to primary and community-based care
      (PCC). CONCLUSIONS: Two distinct strategic orientations in the adoption of PCC
      services by LHAs has emerged from our study. The first has been an investment
      mainly in ambulatory and home-based primary care services in order to increase
      the number of low-complexity settings. A second strategy has prioritized the
      allocation of resources to intermediate inpatient structures for specific types
      of patients, namely elderly and disabled people, post-acute patients in need of
      rehabilitation and long-term care, and patients in hospices.

PMID- 23148627
TI  - Age and gender as determinants of the bone quality of the greater tuberosity: a
      HR-pQCT cadaver study.
AB  - BACKGROUND: Age-dependent trabecular changes of the humeral head might weaken the
      fixation of suture anchors used for rotator cuff (RC) repair. This might lead to
      suture anchor loosening and thus compromise the integrity of the repair. The aim
      of this study was to analyze whether the trabecular microstructure within the RC
      footprint is influenced by age, gender or handedness. METHODS: Axial HR-pQCT
      scans (Scanco Medical) of 64 freshly frozen cadaveric human humeral head
      specimens (age 72.3 +/- 17.4 years) were analyzed to determine the bone volume-to
      total volume ratio (BV/TV), trabecular thickness (Trab Th), trabecular number
      (Trab N) and connectivity density (Conn Dens). Within the RC footprint, 2 volumes
      of interest (VOI), posteromedial (PM) and anterolateral (AL) and one control VOI
      in the subarticular bone (SC) were set. RESULTS: The highest BV/TV was found in
      SC: 0.22 +/- 0.06% vs. PM: 0.04 +/- 0.05% vs. AL: 0.02 +/- 0.04%; p < 0.05. Trab
      Th accounted for 0.26 +/- 0.05 MUm in SC, 0.23 +/- 0.09 MUm in AL and 0.21 +/-
      0.05 MUm in PM. In parallel, Trab N and Conn Dens were found to be the highest in
      SC. Gender analysis yielded higher values for BV/TV, Trab Th, Trab N and Conn
      Dens for PM in males compared to females (p < 0.05). There were no significant
      findings when comparing both sides. We furthermore found a strong inverse
      correlation between age and BV/TV, which was more pronounced in the female
      specimens (r = -0.72, p < 0.00001). CONCLUSIONS: The presented microarchitectural
      data allow for future subtle biomechanical testing comprising knowledge on age-
      and sex-related changes of the tuberosities of the humeral head. Furthermore, the
      insights on the trabecular structure of the humeral head of the elderly may lead
      to the development of new fixation materials in bone with inferior bone quality.

PMID- 23148628
TI  - The future of thiopurine pharmacogenomics.

PMID- 23148629
TI  - Bladder cancer pharmacogenomics: recent insights and future perspectives.

PMID- 23148630
TI  - Influence of the CYP2C9*3 allele on the pharmacological interaction between
      warfarin and simvastatin.
AB  - A letter in response to: Andersson ML, Eliasson E, Lindh JD. A clinically
      significant interaction between warfarin and simvastatin is unique to carriers of
      the CYP2C9*3 allele. Pharmacogenomics 13(7), 757-762 (2012).

PMID- 23148633
TI  - Explanation for HLA-B*57:01-linked immune-mediated abacavir-induced
      hypersensitivity.

PMID- 23148634
TI  - Genetic polymorphisms and novel allelic variants of CYP2C19 in the Chinese Han
      population.
AB  - AIM: This study aims to systematically investigate the genetic polymorphisms of
      the CYP2C19 gene and provide accurate data of the allele distribution pattern in
      the Chinese Han population. MATERIALS & METHODS: We amplified all nine exons of
      the CYP2C19 gene in 2127 unrelated healthy Chinese Han subjects from two
      geographical locations (Zhejiang province, n = 1127; Hebei province, n = 1000),
      using direct sequencing. RESULTS: In total, six previously reported alleles were
      found in our study, in which two alleles CYP2C19*6 and CYP2C19*18 were reported
      for the first time in Chinese Han subjects. In addition, 35 novel variants were
      detected in the present work, which included 11 new named alleles, 12
      nonsynonymous mutations and one insert variant. CONCLUSION: This study provides
      important data on the pattern of CYP2C19 polymorphisms in Chinese Han subjects,
      using the largest group of individuals. Furthermore, the study also detects the
      largest number of novel alleles in one population. These findings are of
      potential benefit to the development of personalized medicine for the Chinese Han
      population.

PMID- 23148635
TI  - Genetic variation in the SLC19A1 gene and methotrexate toxicity in rheumatoid
      arthritis patients.
AB  - AIM: We investigated the clinical relevance of SLC19A1 genetic variability for
      methotrexate (MTX) toxicity in rheumatoid arthritis patients using a haplotype
      based approach. PATIENTS & METHODS: Two hundred and twelve unrelated rheumatoid
      arthritis patients and 89 lymphoblastoid cell lines were used to investigate the
      effect of SLC19A1 SNPs and haplotypes on MTX adverse events and treatment
      discontinuation. RESULTS: Two putatively functional SNPs in high linkage
      disequilibrium, rs1051266 and rs1131596, were associated with protection (hazard
      ratio: 0.33; 95% CI: 0.16-0.69; adjusted p = 0.021 and hazard ratio: 0.38; 95%
      CI: 0.17-0.27; adjusted p = 0.021, respectively) of discontinuation of MTX
      treatment owing to toxicity. These SNPs were also associated with protection from
      infections. SLC19A1 haplotype analysis found significant associations with MTX
      discontinuation owing to toxicity (p = 0.025). Quantification of SLC19A1 mRNA in
      cell lines suggested that rs1131596 was not a major causal variant. CONCLUSION:
      Individual SNP and haplotype analyses suggest that rs1051266 could be a
      functional variant altering MTX toxicity; however, validation in independent
      studies is needed.

PMID- 23148636
TI  - Association of ERCC1 SNPs with outcome in platinum-treated patients with advanced
      urothelial cancer: a Hellenic Cooperative Oncology Group study.
AB  - AIM: The association between two polymorphisms of ERCC1 and treatment outcomes
      after platinum-based chemotherapy in patients with advanced urothelial cancer
      (UC) was examined. MATERIALS & METHODS: Genotyping of 19007C>T and 8092C>A
      polymorphisms was determined by PCR amplification and RFLP in 113 advanced UC
      patients, treated with platinum-based chemotherapy. RESULTS: Seventy eight
      patients (69%) were carriers of the 19007T polymorphic allele: 51 (45%)
      heterozygotes and 27 (24%) homozygotes. Fifty three (47%) patients were carriers
      of the 8092A polymorphic allele: the frequencies of C/A and A/A genotypes were
      37% and 10%, respectively. The T/T genotype was independently associated with
      prolonged median cancer-specific survival (not-reached vs 14.8 months; p =
      0.026). There was no interaction between T/T or any other genotype with the type
      of platinum derivative (cisplatin/carboplatin). CONCLUSION: 19007C>T, especially
      in its homozygotic state, but not 8092C>A polymorphism, could be a useful
      prognostic marker in advanced UC treated with platinum-based chemotherapy.

PMID- 23148638
TI  - Constitutional genetic variants as predictors of antiangiogenic therapy outcome
      in renal cell carcinoma.
AB  - The development of specific angiogenesis inhibitors has drastically improved
      renal cancer treatment in recent years. Currently, four VEGF receptor inhibitors
      (sorafenib, sunitinib, pazopanib and axitinib), one anti-VEGF monoclonal antibody
      (bevacizumab) and two inhibitors of the mTOR pathway (temsirolimus and
      everolimus) have been approved to treat renal cell carcinoma (RCC), and several
      other molecules are under investigation. However, lack of response to
      antiangiogenic drugs and adverse drug reactions leading to treatment suspension
      are critical clinical problems that need to be solved. Because antiangiogenic
      drugs act on nonmalignant endothelial cells, the genetic background of the
      patient may play a crucial role determining the efficacy of these drugs. This
      article focuses on the identification of polymorphisms associated with
      antiangiogenic drugs outcome in RCC patients. It reviews and summarizes our
      current knowledge on this area and discusses future strategies to identify new
      biomarkers that could be used to personalize RCC management.

PMID- 23148637
TI  - Polymorphic thymidylate synthase gene impacts on overall survival of patients
      with epithelial ovarian cancer after platinum-based chemotherapy.
AB  - AIM: High levels of TS have been associated with a worse clinical outcome in
      several cancers including epithelial ovarian cancer (EOC). The TS gene (TYMS) is
      highly polymorphic and has an effect on mRNA/protein expression. MATERIALS &
      METHODS: Six TYMS polymorphisms were investigated for overall survival (OS) in
      216 EOC patients: TYMS 1494ins/del, TSER (variable number of tandem repeats of 28
      bp), TSER G>C, TYMS 1053C>T, TYMS IVS6-68C>T and TYMS 1122A>G. RESULTS: In a
      multivariate analysis, TYMS 1494 del/del genotype was associated with a
      significant increased OS compared with the ins/ins genotype (hazard ratio: 0.36;
      95% CI: 0.16-0.82, p = 0.01). Similar results were obtained for the mutant
      genotypes TYMS 1053TT and TYMS IVS6-68TT. The event-free survival was
      significantly higher in TYMS 1053TT patients compared with wild-type patients (p
      = 0.05). CONCLUSION: TYMS 1494ins/del, 1053C>T and IVS6-68C>T polymorphisms can
      be prognostic markers for OS in patients with EOC, independently from stage at
      diagnosis, median age and tumor histotype.

PMID- 23148639
TI  - miRNA pharmacogenomics: the new frontier for personalized medicine in cancer?
AB  - In recent years pharmacogenomic research has highlighted several genetic
      biomarkers of treatment toxicity and efficacy, dealing with drug metabolism,
      transport and mechanism of action. More recently, polymorphisms in miRNA encoding
      genes, their targets or factors involved in their maturation are rising as new
      pharmacogenomic markers in cancer. miRNAs are brief ncRNAs involved in DNA
      translational control, with an effect on mRNA and protein-expression levels. The
      study of genetic polymorphisms in genes involved in miRNA translational control
      machinery could give innovative insights in pharmacogenomics. This review
      summarizes the most recent and promising results in the field and gives an
      overview of the future perspective of personalized cancer therapy.

PMID- 23148640
TI  - Building bridges to the future of medicine: recommendations for boosting
      development of novel and companion diagnostics.
AB  - Evaluating the prospects for 'personalized healthcare' has become topical at the
      10-year anniversary of the first results from the Human Genome Project. The
      coincidence of this milestone with a period of global financial difficulty is
      unfortunate, but industry has signaled its willingness to invest in this new
      medical paradigm in order to address the problems of high drug candidate
      attrition as well as escalating healthcare and R&D costs. For diagnostics
      manufacturers, justifying the ever-growing costs of development without an
      appropriate framework to provide reasonable return on investment is extremely
      challenging. Regulators have made good progress in defining what will satisfy
      current regulatory mandates, but there is still far to go to create conditions
      that would stimulate investment. My personal perspective is that personalized
      healthcare represents a solution rather than a problem and herein I describe the
      bottlenecks slowing development of novel diagnostics from the perspective of a
      willing commercial stakeholder.

PMID- 23148643
TI  - Tagmatization in Stomatopoda - reconsidering functional units of modern-day
      mantis shrimps (Verunipeltata, Hoplocarida) and implications for the
      interpretation of fossils.
AB  - INTRODUCTION: We describe the tagmatization pattern of the anterior region of
      the extant stomatopod Erugosquilla massavensis. For documentation we used the
      autofluorescence capacities of the specimens, resulting in a significant contrast
      between sclerotized and membranous areas. RESULTS: The anterior body region of E.
      massavensis can be grouped into three tagmata. Tagma I, the sensorial unit,
      comprises the segments of the eyes, antennules and antennae. This unit is set-off
      anteriorly from the posterior head region. Ventrally this unit surrounds a large
      medial sclerite, interpreted as the anterior part of the hypostome. Dorsally the
      antennular and antennal segments each bear a well-developed tergite. The dorsal
      shield is part of tagma II, most of the ventral part of which is occupied in the
      midline by the large, partly sclerotized posterior part of a complex combining
      hypostome and labrum. Tagma II includes three more segments behind the labrum,
      the mandibular, maxillulary and maxillary segments. Tagma III includes the
      maxillipedal segments, bearing five pairs of sub-chelate appendages. The dorsal
      sclerite of the first of these tagma-III segments, the segment of the first
      maxillipeds, is not included in the shield, so this segment is not part of tagma
      II as generally thought. The second and third segments of tagma III form a unit
      dorsally and ventrally. The tergites of the segments of tagma III become
      progressively larger from the anterior to the posterior, possibly resulting from
      a paedomorphic effect during evolution, which caused this reversed enlargement.
      CONCLUSIONS: The described pattern of tagmosis differs from current textbook
      knowledge. Therefore, our re-description of the anterior body area of stomatopods
      is of considerable impact for understanding the head evolution of Stomatopoda.
      Likewise, it has a bearing upon any comparisons with fossil stomatopods, as
      mainly sclerotized areas are fossilized, and, on a wider scale, upon larger-scale
      comparisons with other malacostracans and eucrustaceans in general.

PMID- 23148644
TI  - On the mechanisms of triplet excited state population in 8-azaadenine.
AB  - The photophysics of 8-azaadenine (8-AA) has been studied with the CASPT2//CASSCF
      protocol and ANO-L double-zeta basis sets. Stationary equilibrium structures,
      surface crossings, minimum energy paths, and linear interpolations have been used
      to study possible mechanisms to populate the lowest triplet state,
      T(1)(3)(pipi*), capable of sensitizing molecular oxygen. Our results show that
      two main mechanisms can occur after photoexcitation to the S(2)(1)(pipi*) state.
      The first one is through the S(2)/S(1) conical intersection
      (((1)pipi*/(1)npi*)(CI)), leading to the S(1) ((1)npi*) state minimum, (S(1)
      ((1)npi*))(min), where a singlet-triplet crossing, ((1)npi*/(3)pipi*)(STC), is
      accessible. The second one starts with the ((1)pipi*/(3)npi*)(STC) at the
      (S(2)((1)pipi*))(min), from which the system can evolve to the (T(2)
      ((3)npi*))(min), with subsequent population of the T(1) excited electronic state,
      due to the ((3)npi*/(3)pipi*)(CI) conical intersection.

PMID- 23148642
TI  - Transcriptome analysis of the spalax hypoxia survival response includes
      suppression of apoptosis and tight control of angiogenesis.
AB  - BACKGROUND: The development of complex responses to hypoxia has played a key role
      in the evolution of mammals, as inadequate response to this condition is
      frequently associated with cardiovascular diseases, developmental disorders, and
      cancers. Though numerous studies have used mice and rats in order to explore
      mechanisms that contribute to hypoxia tolerance, these studies are limited due to
      the high sensitivity of most rodents to severe hypoxia. The blind subterranean
      mole rat Spalax is a hypoxia tolerant rodent, which exhibits unique longevity and
      therefore has invaluable potential in hypoxia and cancer research. RESULTS: Using
      microarrays, transcript abundance was measured in brain and muscle tissues from
      Spalax and rat individuals exposed to acute and chronic hypoxia for varying
      durations. We found that Spalax global gene expression response to hypoxia
      differs from that of rat and is characterized by the activation of functional
      groups of genes that have not been strongly associated with the response to
      hypoxia in hypoxia sensitive mammals. Using functional enrichment analysis of
      Spalax hypoxia induced genes we found highly significant overrepresentation of
      groups of genes involved in anti apoptosis, cancer, embryonic/sexual development,
      epidermal growth factor receptor binding, coordinated suppression and activation
      of distinct groups of transcription factors and membrane receptors, in addition
      to angiogenic related processes. We also detected hypoxia induced increases of
      different critical Spalax hub gene transcripts, including antiangiogenic genes
      associated with cancer tolerance in Down syndrome human individuals. CONCLUSIONS:
      This is the most comprehensive study of Spalax large scale gene expression
      response to hypoxia to date, and the first to use custom Spalax microarrays. Our
      work presents novel patterns that may underlie mechanisms with critical
      importance to the evolution of hypoxia tolerance, with special relevance to
      medical research.

PMID- 23148646
TI  - Cutting and unzipping multiwalled carbon nanotubes into curved graphene
      nanosheets and their enhanced supercapacitor performance.
AB  - We report a remarkable transformation of multiwalled carbon nanotubes (MWCNTs) to
      curved graphene nanosheets (CGN) by the Hummers method. Through this simple
      process, MWCNTs can be cut and unzipped in the transverse and longitudinal
      directions, respectively. The as-obtained CGN possess the unique hybrid structure
      of 1D nanotube and 2D graphene. Such a particular structure together with the
      improved effective surface area affords high specific capacitance and good
      cycling stability during the charge-discharge process when used as supercapacitor
      electrodes. The electrochemical measurements show that CGN exhibit higher
      capacitive properties than pristine MWCNTs in three different types of aqueous
      electrolytes, 1 M KOH, 1 M H(2)SO(4), and 1 M Na(2)SO(4). A specific capacitance
      of as high as 256 F g(-1) at a current density of 0.3 A g(-1) is achieved over
      the CGN material. The improved capacitance may be attributed to high
      accessibility to electrolyte ions, extended defect density, and increased
      effective surface area. Meanwhile, this high-yield production of graphene from
      low cost MWCNTs is important for the scalable synthesis and industrial
      application of graphene. Furthermore, this novel CGN nanostructure could also be
      promisingly applied in many fields such as nanoelectronics, sensors,
      nanocomposites, batteries, and gas storage.

PMID- 23148645
TI  - Flagellar display of bone-protein-derived peptides for studying peptide-mediated
      biomineralization.
AB  - A bacterial flagellum is self-assembled primarily from thousands of flagellin
      (FliC), a protein subunit. A foreign peptide can be fully displayed on the
      surface of the flagellum through inserting it into every constituent protein
      subunit. To shed light on the role of bone proteins during the nucleation of
      hydroxyapatite (HAP), representative domains from type I collagen, including part
      of the N-,C-terminal, N-,C-zone around the hole zone and an eight repeat unit Gly
      Pro-Pro (GPP8) sequence similar to the central sequence of type I collagen, were
      separately displayed on the surface of the flagella. Moreover, eight negatively
      charged, contiguous glutamic acid residues (E8) and two other characteristic
      sequences derived from a representative noncollagenous protein called bone
      sialoprotein (BSP) were also displayed on flagella. After being incubated in an
      HAP supersaturated precursor solution, flagella displaying E8 or GPP8 sequences
      were found to be coated with a layer of HAP nanocrystals. Very weak or no
      nucleation was observed on flagella displaying other peptides being tested. We
      also found that calcium ions can induce the assembly of the negatively charged E8
      flagella into bundles mimicking collagen fibers, followed by the formation of HAP
      nanocrystals with the crystallographic c axis preferentially aligned with long
      axis of flagella, which is similar to that along the collagen fibrils in bone.
      This work demonstrates that because of the ease of the peptide display on
      flagella and the self-assembly of flagella, flagella can serve as a platform for
      studying biomineralization and as a building block to generate bonelike
      biomaterials.

PMID- 23148647
TI  - The development and validation of the Dieting Intentions Scale (DIS).
AB  - This article presents information on the psychometric properties of the Dieting
      Intentions Scale (DIS), a new scale of dieting that predicts future behavioral
      efforts to lose weight. We begin by reviewing recent research indicating
      theoretical and empirical problems with traditional approaches to measuring
      dieting. The DIS addresses several of these problems by (a) focusing on
      naturalistic dieting behavior and (b) being future-oriented. Four validation
      studies are presented with a total of 741 participants. We demonstrate that the
      DIS has predictive utility for dieting behaviors and is positively correlated
      with other measures related to eating, weight, and shape. Furthermore, the DIS
      demonstrates discriminant validity by not being related to constructs such as
      self-esteem and social desirability. The DIS also has high internal consistency,
      with a 1-factor solution replicated with confirmatory factor analysis. The
      potential uses of the scale in both research and clinical settings are
      considered.

PMID- 23148648
TI  - Formulation of the age-education index: measuring age and education effects in
      neuropsychological performance.
AB  - The complex interplay of education, age, and cognitive performance on various
      neuropsychological tests is examined in the current study. New education indices
      were formulated and further investigated to reveal how age and education
      variances work together to account for performance on neuropsychological tests.
      Participants were 830 English-speaking ethnic Chinese. Neuropsychological
      measures such as Verbal Memory, Digit Sequencing, Token Motor Task, Semantic
      Fluency, Symbol Coding, Tower of London, Judgment of Line Orientation, and Matrix
      Reasoning of the Wechsler Adult Intelligence Scale were administered. Education
      was measured by total years of education and adjusted years of education, as well
      as ratios of both measures with age. Age and education were associated with
      neuropsychological performance. Adjusted years of education was associated with
      fluency and higher cognitive processes, while the ratio between adjusted years of
      education and age was associated with tasks implicating working memory. Changes
      in education modalities implicated tasks requiring language abilities. Education
      and age represent key neurodevelopmental milestones. In light of our findings,
      special consideration should to be given when neuropsychological assessments are
      carried out in cross-cultural contexts and in societies where educational systems
      and pedagogy tend to be complex.

PMID- 23148649
TI  - New tricks for an old measure: the development of the Barratt Impulsiveness Scale
      Brief (BIS-Brief).
AB  - The Barratt Impulsivity Scale (BIS), a 30-item self-report measure, is one of the
      most commonly used scales for the assessment of the personality construct of
      impulsiveness. It has recently marked 50 years of use in research and clinical
      settings. The current BIS-11 is held to measure 3 theoretical subtraits, namely,
      attentional, motor, and non-planning impulsiveness. We evaluated the factor
      structure of the BIS using full information item bifactor analysis for Likert
      type items. We found no evidence supporting the 3-factor model. In fact, half of
      the items do not share any relation with other items and do not form any factor.
      In light of this, we introduce a unidimensional Barratt Impulsiveness Scale-Brief
      (BIS-Brief) that includes 8 of the original BIS-11 items. Next, we present
      evidence of construct validity comparing scores obtained with the BIS-Brief
      against the original BIS total scores using data from (a) a community sample of
      borderline personality patients and normal controls, (b) a forensic sample, and
      (c) an inpatient sample of young adults and adolescents. We demonstrated similar
      indices of construct validity that is observed for the BIS-11 total score with
      the BIS-Brief score. Use of the BIS-Brief in clinical assessment settings and
      large epidemiological studies of psychiatric disorders will reduce the burden on
      respondents without loss of information.

PMID- 23148651
TI  - Further insights on the French WISC-IV factor structure through Bayesian
      structural equation modeling.
AB  - The interpretation of the Wechsler Intelligence Scale for Children--Fourth
      Edition (WISC-IV) is based on a 4-factor model, which is only partially
      compatible with the mainstream Cattell-Horn-Carroll (CHC) model of intelligence
      measurement. The structure of cognitive batteries is frequently analyzed via
      exploratory factor analysis and/or confirmatory factor analysis. With classical
      confirmatory factor analysis, almost all cross-loadings between latent variables
      and measures are fixed to zero in order to allow the model to be identified.
      However, inappropriate zero cross-loadings can contribute to poor model fit,
      distorted factors, and biased factor correlations; most important, they do not
      necessarily faithfully reflect theory. To deal with these methodological and
      theoretical limitations, we used a new statistical approach, Bayesian structural
      equation modeling (BSEM), among a sample of 249 French-speaking Swiss children (8
      12 years). With BSEM, zero-fixed cross-loadings between latent variables and
      measures are replaced by approximate zeros, based on informative, small-variance
      priors. Results indicated that a direct hierarchical CHC-based model with 5
      factors plus a general intelligence factor better represented the structure of
      the WISC-IV than did the 4-factor structure and the higher order models. Because
      a direct hierarchical CHC model was more adequate, it was concluded that the
      general factor should be considered as a breadth rather than a superordinate
      factor. Because it was possible for us to estimate the influence of each of the
      latent variables on the 15 subtest scores, BSEM allowed improvement of the
      understanding of the structure of intelligence tests and the clinical
      interpretation of the subtest scores.

PMID- 23148650
TI  - Rorschach measures of cognition relate to everyday and social functioning in
      schizophrenia.
AB  - Neurocognitive impairment and negative symptoms contribute to functional
      disability in people with schizophrenia. Yet, a high level of unexplained
      variability remains after accounting for the role of these factors. This study
      examined the role of thought disorder, psychological complexity, and
      interpersonal representations, as measured by the Rorschach, in explaining
      functional and social skills capacity in 72 middle-aged and older outpatients
      with schizophrenia (mean age = 51.2 years). Participants responded to the
      Rorschach administered with the R-Optimized administration instructions and
      scored with the Rorschach Performance Assessment System. Relationships with
      neuropsychological performance and psychopathology were also explored.
      Psychological complexity, which refers to a person's cognitive capacity for
      problem solving and organizing his or her surroundings, was correlated with
      functional capacity (r = .30) and social skills capacity (r = .34). Healthy
      interpersonal representations were correlated with positive social skills (rs =
      .24-.28). In multiple regression models, psychological complexity accounted for
      significant variation in functional (beta = .23, p = .02) and social skills
      capacity (beta = .35, p < .01) after controlling for neurocognitive functioning
      and psychopathology. These data suggest that psychological complexity plays a
      significant role in the functional limitations seen in schizophrenia, above and
      beyond the contributions of neurocognitive impairment and negative symptoms.
      Support was also found for the impact of healthy object relations functioning
      with social functioning. Clinical implications include novel information for
      future development of cognitive remediation treatment strategies based on a
      patient's developmental level of psychological capacity and healthy interpersonal
      schemas.

PMID- 23148652
TI  - Solid-phase total synthesis of cherimolacyclopeptide E and discovery of more
      potent analogues by alanine screening.
AB  - Cherimolacyclopeptide E (1) is a cyclic hexapeptide obtained from Annona
      cherimola, reported to be cytotoxic against the KB (human nasopharyngeal
      carcinoma) cell line. The solid-phase total syntheses of this cyclic peptide and
      its analogues were accomplished by employing FMOC/tert-butyl-protected amino
      acids and the Kenner sulfonamide safety-catch linker. The synthetic peptide 1 was
      found to be weakly cytotoxic against four cell lines (MOLT-4, Jurkat T lymphoma,
      MDA-MB-231, and KB). Analogues 3 and 7, where glycine at positions 2 and 6 of the
      parent compound was replaced by Ala, exhibited enhanced cytotoxicity against KB
      (3, IC50 6.3 MUM; 7, IC50 7.8 MUM) and MDA-MB-231 breast cancer cells (3, IC50
      10.2 MUM; 7, IC50 7.7 MUM), thereby suggesting possible selective targeting of
      these cancer cells by these peptides. The spectral data of synthetic peptide 1
      was found to be similar to that reported for the natural product. However, a
      striking difference in biological activity was noted, which warrants the re
      evaluation of the original natural product for purity and the existence of
      conformational differences. 

PMID- 23148654
TI  - Pandemic influenza A/H1N1 virus infection and TNF, LTA, IL1B, IL6, IL8, and CCL
      polymorphisms in Mexican population: a case-control study.
AB  - BACKGROUND: Some patients have a greater response to viral infection than do
      others having a similar level of viral replication. Hypercytokinemia is the
      principal immunopathological mechanism that contributes to a severer clinical
      course in cases of influenza A/H1N1. The benefit produced, or damage caused, by
      these cytokines in severe disease is not known. The genes that code for these
      molecules are polymorphic and certain alleles have been associated with
      susceptibility to various diseases. The objective of the present study was to
      determine whether there was an association between polymorphisms of TNF, LTA,
      IL1B, IL6, IL8, and CCL1 and the infection and severity of the illness caused by
      the pandemic A/H1N1 in Mexico in 2009. METHODS: Case-control study. The cases
      were patients confirmed with real time PCR with infection by the A/H1N1 pandemic
      virus. The controls were patients with infection like to influenza and non
      familial healthy contacts of the patients with influenza. Medical history and
      outcome of the disease was registered. The DNA samples were genotyped for
      polymorphisms TNF rs361525, rs1800629, and rs1800750; LTA rs909253; IL1B rs16944;
      IL6 rs1818879; IL8 rs4073; and CCL1 rs2282691. Odds ratio (OR) and the 95%
      confidence interval (95% CI) were calculated. The logistic regression model was
      adjusted by age and severity of the illness in cases. RESULTS: Infection with the
      pandemic A/H1N1 virus was associated with the following genotypes: TNF rs361525
      AA, OR = 27.00; 95% CI = 3.07-1248.77); LTA rs909253 AG (OR = 4.33, 95% CI = 1.82
      10.32); TNF rs1800750 AA (OR = 4.33, 95% CI = 1.48-12.64); additionally, LTA
      rs909253 AG showed a limited statistically significant association with mortality
      (p = 0.06, OR = 3.13). Carriers of the TNF rs1800629 GA genotype were associated
      with high levels of blood urea nitrogen (p = 0.05); those of the TNF rs1800750 AA
      genotype, with high levels of creatine phosphokinase (p=0.05). The IL1B rs16944
      AA genotype was associated with an elevated number of leukocytes (p <0.001) and
      the IL8 rs4073 AA genotype, with a higher value for PaO2 mm Hg. CONCLUSION: The
      polymorphisms of genes involved in the inflammatory process contributed to the
      severity of the clinical behavior of infection by the pandemic influenza A/H1N1
      virus.

PMID- 23148653
TI  - An Always Correlated gene expression landscape for ovine skeletal muscle, lessons
      learnt from comparison with an "equivalent" bovine landscape.
AB  - BACKGROUND: We have recently described a method for the construction of an
      informative gene expression correlation landscape for a single tissue,
      longissimus muscle (LM) of cattle, using a small number (less than a hundred) of
      diverse samples. Does this approach facilitate interspecies comparison of
      networks? FINDINGS: Using gene expression datasets from LM samples from a single
      postnatal time point for high and low muscling sheep, and from a developmental
      time course (prenatal to postnatal) for normal sheep and sheep exhibiting the
      Callipyge muscling phenotype gene expression correlations were calculated across
      subsets of the data comparable to the bovine analysis. An "Always Correlated"
      gene expression landscape was constructed by integrating the correlations from
      the subsets of data and was compared to the equivalent landscape for bovine LM
      muscle. Whilst at the high level apparently equivalent modules were identified in
      the two species, at the detailed level overlap between genes in the equivalent
      modules was limited and generally not significant. Indeed, only 395 genes and 18
      edges were in common between the two landscapes. CONCLUSIONS: Since it is
      unlikely that the equivalent muscles of two closely related species are as
      different as this analysis suggests, within tissue gene expression correlations
      appear to be very sensitive to the samples chosen for their construction,
      compounded by the different platforms used. Thus users need to be very cautious
      in interpretation of the differences. In future experiments, attention will be
      required to ensure equivalent experimental designs and use cross-species gene
      expression platform to enable the identification of true differences between
      different species.

PMID- 23148655
TI  - Reliability and validity of the Wolfram Unified Rating Scale (WURS).
AB  - BACKGROUND: Wolfram syndrome (WFS) is a rare, neurodegenerative disease that
      typically presents with childhood onset insulin dependent diabetes mellitus,
      followed by optic atrophy, diabetes insipidus, deafness, and neurological and
      psychiatric dysfunction. There is no cure for the disease, but recent advances in
      research have improved understanding of the disease course. Measuring disease
      severity and progression with reliable and validated tools is a prerequisite for
      clinical trials of any new intervention for neurodegenerative conditions. To this
      end, we developed the Wolfram Unified Rating Scale (WURS) to measure the severity
      and individual variability of WFS symptoms. The aim of this study is to develop
      and test the reliability and validity of the Wolfram Unified Rating Scale (WURS).
      METHODS: A rating scale of disease severity in WFS was developed by modifying a
      standardized assessment for another neurodegenerative condition (Batten disease).
      WFS experts scored the representativeness of WURS items for the disease. The WURS
      was administered to 13 individuals with WFS (6-25 years of age). Motor, balance,
      mood and quality of life were also evaluated with standard instruments. Inter
      rater reliability, internal consistency reliability, concurrent, predictive and
      content validity of the WURS were calculated. RESULTS: The WURS had high inter
      rater reliability (ICCs>.93), moderate to high internal consistency reliability
      (Cronbach's alpha = 0.78-0.91) and demonstrated good concurrent and predictive
      validity. There were significant correlations between the WURS Physical
      Assessment and motor and balance tests (rs>.67, p<.03), between the WURS
      Behavioral Scale and reports of mood and behavior (rs>.76, p<.04) and between
      WURS Total scores and quality of life (rs=-.86, p=.001). The WURS demonstrated
      acceptable content validity (Scale-Content Validity Index=0.83). CONCLUSIONS:
      These preliminary findings demonstrate that the WURS has acceptable reliability
      and validity and captures individual differences in disease severity in children
      and young adults with WFS.

PMID- 23148656
TI  - Predicting chemical ocular toxicity using a combinatorial QSAR approach.
AB  - Regulatory agencies require testing of chemicals and products to protect workers
      and consumers from potential eye injury hazards. Animal screening, such as the
      rabbit Draize test, for potential environmental toxicants is time-consuming and
      costly. Therefore, virtual screening using computational models to tag potential
      ocular toxicants is attractive to toxicologists and policy makers. We have
      developed quantitative structure-activity relationship (QSAR) models for a set of
      small molecules with animal ocular toxicity data compiled by the National
      Toxicology Program Interagency Center for the Evaluation of Alternative
      Toxicological Methods. The data set was initially curated by removing duplicates,
      mixtures, and inorganics. The remaining 75 compounds were used to develop QSAR
      models. We applied both k nearest neighbor and random forest statistical
      approaches in combination with Dragon and Molecular Operating Environment
      descriptors. Developed models were validated on an external set of 34 compounds
      collected from additional sources. The external correct classification rates
      (CCR) of all individual models were between 72 and 87%. Furthermore, the
      consensus model, based on the prediction average of individual models, showed
      additional improvement (CCR = 0.93). The validated models could be used to screen
      external chemical libraries and prioritize chemicals for in vivo screening as
      potential ocular toxicants.

PMID- 23148657
TI  - From the first cry to development of the study of reproductive health in Japan: A
      tribute to Sei-ichi Matsumoto.

PMID- 23148659
TI  - Contributions of mutations in acrR and marR genes to organic solvent tolerance in
      Escherichia coli.
AB  - The AcrAB-TolC efflux pump is involved in maintaining intrinsic organic solvent
      tolerance in Escherichia coli. Mutations in regulatory genes such as marR, soxR,
      and acrR are known to increase the expression level of the AcrAB-TolC pump. To
      identify these mutations in organic solvent tolerant E. coli, eight cyclohexane
      tolerant E. coli JA300 mutants were isolated and examined by DNA sequencing for
      mutations in marR, soxR, and acrR. Every mutant carried a mutation in either marR
      or acrR. Among all mutants, strain CH7 carrying a nonsense mutation in marR
      (named marR109) and an insertion of IS5 in acrR, exhibited the highest organic
      solvent-tolerance levels. To clarify the involvement of these mutations in
      improving organic solvent tolerance, they were introduced into the E. coli JA300
      chromosome by site-directed mutagenesis using lambda red-mediated homologous
      recombination. Consequently, JA300 mutants carrying acrR::IS5, marR109, or both
      were constructed and named JA300 acrRIS, JA300 marR, or JA300 acrRIS marR,
      respectively. The organic solvent tolerance levels of these mutants were
      increased in the following order: JA300 < JA300 acrRIS < JA300 marR < JA300
      acrRIS marR. JA300 acrRIS marR formed colonies on an agar plate overlaid with
      cyclohexane and p-xylene (6:4 vol/vol mixture). The organic solvent-tolerance
      level and AcrAB-TolC efflux pump-expression level in JA300 acrRIS marR were
      similar to those in CH7. Thus, it was shown that the synergistic effects of
      mutations in only two regulatory genes, acrR and marR, can significantly increase
      organic solvent tolerance in E. coli.

PMID- 23148658
TI  - Functional analysis of Arabidopsis mutants points to novel roles for glutathione
      in coupling H(2)O(2) to activation of salicylic acid accumulation and signaling.
AB  - AIMS: Through its interaction with H(2)O(2), glutathione is a candidate for
      transmission of signals in plant responses to pathogens, but identification of
      signaling roles is complicated by its antioxidant function. Using a genetic
      approach based on a conditional catalase-deficient Arabidopsis mutant, cat2, this
      study aimed at establishing whether GSH plays an important functional role in the
      transmission of signals downstream of H(2)O(2). RESULTS: Introducing the cad2 or
      allelic mutations in the glutathione synthesis pathway into cat2 blocked H(2)O(2)
      triggered GSH oxidation and accumulation. While no effects on NADP(H) or
      ascorbate were observed, and H(2)O(2)-induced decreases in growth were
      maintained, blocking GSH modulation antagonized salicylic acid (SA) accumulation
      and SA-dependent responses. Other novel double and triple mutants were produced
      and compared with cat2 cad2 at the levels of phenotype, expression of marker
      genes, nontargeted metabolite profiling, accumulation of SA, and bacterial
      resistance. Most of the effects of the cad2 mutation on H(2)O(2)-triggered
      responses were distinct from those produced by mutations for GLUTATHIONE
      REDUCTASE1 (GR1) or NONEXPRESSOR OF PATHOGENESIS-RELATED GENES 1 (NPR1), and were
      linked to compromised induction of ISOCHORISMATE SYNTHASE1 (ICS1) and ICS1
      dependent SA accumulation. INNOVATION: A novel genetic approach was used in which
      GSH content or antioxidative capacity was independently modified in an H(2)O(2)
      signaling background. Analysis of new double and triple mutants allowed us to
      infer previously undescribed regulatory roles for GSH. CONCLUSION: In parallel to
      its antioxidant role, GSH acts independently of NPR1 to allow increased
      intracellular H(2)O(2) to activate SA signaling, a key defense response in
      plants.

PMID- 23148660
TI  - Contrast-enhanced harmonic endoscopic ultrasound is able to discriminate benign
      submucosal lesions from gastrointestinal stromal tumors.
AB  - BACKGROUND: Although endoscopic ultrasound (EUS) has improved the diagnostic of
      potential malignancies, gastric lesions with suspicion of gastrointestinal
      stromal tumors (GIST) or benign lesions like lipoma or leiomyoma can often not be
      accurately differentiated by EUS, therefore, requiring tissue sampling with the
      risk of bleeding complications especially in GIST. As with the newest generation
      of EUS machines, contrast-enhanced harmonic endoscopic ultrasound (CEH-EUS) has
      become a new option to determine perfusion characteristics. The aim of this
      analysis was to evaluate whether CEH-EUS may help to discriminate various
      submucosal lesions. METHODS: Data sets of 17 patients with suspicious gastric or
      esophageal lesions, who were investigated with CEH-EUS were analyzed. Perfusion
      characteristics were classified by the investigator immediately and statistically
      analyzed after investigation. Samples from EUS-fine needle aspirates, biopsy
      samples after needle cut or surgical specimen served as gold standard. RESULTS:
      CEH-EUS showed nine lesions with reduced contrast enhancement (maximum intensity
      6.2 +/- 1.9 db) and eight lesions with hyperenhancement (47.3 +/- 11.6 db). The
      latter eight lesions were all histologically identified as GIST, while the nine
      hypoenhanced lesions emerged to be four lipoma and five leiomyoma. Statistical
      analysis corresponded with initial perfusion classification in all cases.
      CONCLUSION: This is the first study showing that CEH-EUS can discriminate GIST
      from benign lesions with good accuracy. In the future, CEH-EUS-guided
      discrimination may lead to individualized diagnostic and therapeutic strategies
      in handling submucosal lesions.

PMID- 23148661
TI  - Enhancing solubility of deoxyxylulose phosphate pathway enzymes for microbial
      isoprenoid production.
AB  - BACKGROUND: Recombinant proteins are routinely overexpressed in metabolic
      engineering. It is well known that some over-expressed heterologous recombinant
      enzymes are insoluble with little or no enzymatic activity. This study examined
      the solubility of over-expressed homologous enzymes of the deoxyxylulose
      phosphate pathway (DXP) and the impact of inclusion body formation on metabolic
      engineering of microbes. RESULTS: Four enzymes of this pathway (DXS, ISPG, ISPH
      and ISPA), but not all, were highly insoluble, regardless of the expression
      systems used. Insoluble dxs (the committed enzyme of DXP pathway) was found to be
      inactive. Expressions of fusion tags did not significantly improve the solubility
      of dxs. However, hypertonic media containing sorbitol, an osmolyte, successfully
      doubled the solubility of dxs, with the concomitant improvement in microbial
      production of the metabolite, DXP. Similarly, sorbitol significantly improved the
      production of soluble and functional ERG12, the committed enzyme in the
      mevalonate pathway. CONCLUSION: This study demonstrated the unanticipated
      findings that some over-expressed homologous enzymes of the DXP pathway were
      highly insoluble, forming inclusion bodies, which affected metabolite formation.
      Sorbitol was found to increase both the solubility and function of some of these
      over-expressed enzymes, a strategy to increase the production of secondary
      metabolites.

PMID- 23148663
TI  - Pattern of spread to the lateral neck in metastatic well-differentiated thyroid
      cancer: a systematic review and meta-analysis.
AB  - BACKGROUND: There remains controversy surrounding the extent of lateral neck
      dissection required in patients with papillary thyroid cancer (PTC) and
      suspicious or confirmed metastatic lateral neck lymphadenopathy. The evidence for
      this clinical dilemma has never been reviewed systematically nor has there been
      an attempt to meta-analyze the data by lymph node levels to better characterize
      the pattern of spread. METHODS: This meta-analysis used MEDLINE and EMBASE
      including all cohort studies reporting the pattern of lateral neck disease in
      patients who underwent a neck dissection for clinically, radiographically, or
      cytologically suspicious or confirmed metastatic lymphadenopathy for PTC. Our
      main outcome was the number of patients with positive involvement at a given
      level as a percentage of the cohort of patients with positive lateral neck
      disease, each level being measured separately. RESULTS: Eighteen studies with a
      total of 1145 patients and 1298 neck dissections were included in our meta
      analysis. Levels IIa and IIb had disease in 53.1% [95% confidence interval (CI)
      46.6-59.5%] and 15.5% [CI 8.2-27.2%], respectively. Studies that did not
      distinguish between level IIa and IIb or in which both were collapsed into one
      category showed a total level II involvement of 53.4% [CI 49.7-57.1%]. Level III
      and level IV were involved in 70.5% [CI 67.0-73.9%] and 66.3% [CI 61.4-70.9%] of
      specimens. Studies that did not distinguish between level Va and Vb or in which
      both were collapsed into one category showed a total level V involvement of 25.3%
      [CI 20.0-31.5%]. Levels Va and Vb had positivity in 7.9% [CI 2.8-20.0%] and 21.5%
      [CI 7.7-47.6%], respectively, but had only three studies that could be meta
      analyzed. CONCLUSIONS: This systematic review of the literature and meta-analysis
      of the pattern of spread indicates significant rates of lymph node metastasis to
      all lateral neck levels in patients with PTC with regional involvement. This
      evidence leads us to recommend a comprehensive selective neck dissection of
      levels IIa, IIb, III, IV, and Vb in patients with lateral neck disease from PTC.
      The evidence for level Va is lacking, as most studies did not distinguish between
      levels Va and Vb, and the border between the two levels was inconsistent. Future
      studies will need to address these sublevels separately.

PMID- 23148662
TI  - Targeted DNA excision in Arabidopsis by a re-engineered homing endonuclease.
AB  - BACKGROUND: A systematic method for plant genome manipulation is a major aim of
      plant biotechnology. One approach to achieving this involves producing a double
      strand DNA break at a genomic target site followed by the introduction or removal
      of DNA sequences by cellular DNA repair. Hence, a site-specific endonuclease
      capable of targeting double-strand breaks to unique locations in the plant genome
      is needed. RESULTS: We engineered and tested a synthetic homing endonuclease,
      PB1, derived from the I-CreI endonuclease of Chlamydomonas reinhardtii, which was
      re-designed to recognize and cleave a newly specified DNA sequence. We
      demonstrate that an activity-optimized version of the PB1 endonuclease, under the
      control of a heat-inducible promoter, is capable of targeting DNA breaks to an
      introduced PB1 recognition site in the genome of Arabidopsis thaliana. We further
      demonstrate that this engineered endonuclease can very efficiently excise
      unwanted transgenic DNA, such as an herbicide resistance marker, from the genome
      when the marker gene is flanked by PB1 recognition sites. Interestingly, under
      certain conditions the repair of the DNA junctions resulted in a conservative
      pairing of recognition half sites to remove the intervening DNA and reconstitute
      a single functional recognition site. CONCLUSION: These results establish
      parameters needed to use engineered homing endonucleases for the modification of
      endogenous loci in plant genomes.

PMID- 23148664
TI  - Systematic investigation of insertional and deletional RNA-DNA differences in the
      human transcriptome.
AB  - BACKGROUND: The genomic information which is transcribed into the primary RNA can
      be altered by RNA editing at the transcriptional or post-transcriptional level,
      which provides an effective way to create transcript diversity in an organism.
      Altering can occur through substitutional RNA editing or via the insertion or
      deletion of nucleotides relative to the original template. Taking advantage of
      recent high throughput sequencing technology combined with bioinformatics tools,
      several groups have recently studied the genome-wide substitutional RNA editing
      profiles in human. However, while insertional/deletional (indel) RNA editing is
      well known in several lower species, only very scarce evidence supports the
      existence of insertional editing events in higher organisms such as human, and no
      previous work has specifically focused on indel differences between RNA and their
      matching DNA in human. Here, we provide the first study to examine the
      possibility of genome-wide indel RNA-DNA differences in one human individual,
      NA12878, whose RNA and matching genome have been deeply sequenced. RESULTS: We
      apply different computational tools that are capable of identifying indel
      differences between RNA reads and the matching reference genome and we initially
      find hundreds of such indel candidates. However, with careful further analysis
      and filtering, we conclude that all candidates are false-positives created by
      splice junctions, paralog sequences, diploid alleles, and known genomic indel
      variations. CONCLUSIONS: Overall, our study suggests that indel RNA editing
      events are unlikely to exist broadly in the human transcriptome and emphasizes
      the necessity of a robust computational filter pipeline to obtain high confidence
      RNA-DNA difference results when analyzing high throughput sequencing data as
      suggested in the recent genome-wide RNA editing studies.

PMID- 23148665
TI  - Earliest stage of the tetrahedral nanochannel formation in cubosome particles
      from unilamellar nanovesicles.
AB  - Studies of nonequilibrium lipid polymorphism at the nanoscale contribute to the
      in-depth understanding of the structural pathways for formation of aqueous
      channels and emerging of channels-network ordering in liquid-crystalline (LC)
      nanovehicles. We present experimental structural evidence for the smallest
      tetrahedral-type lipid membrane aggregate, which involves completely formed
      nanochannels and occurs as an early intermediate state during the bilayer vesicle
      to-cubosome particle transition. Nanovehicles are generated from a self-assembled
      lipid mixture and studied by means of high-resolution cryogenic transmission
      electron microscopy (cryo-TEM) and synchrotron radiation small-angle X-ray
      scattering (SAXS). The investigated lipid membrane composition allows for the
      stabilization of long-lived intermediates throughout the unilamellar vesicle-to
      cubosome nanoparticle (NP) transformation at ambient temperature. The observed
      small cubosomic particles, with well-defined water channels, appear to be
      precursors of larger cubic membrane structures, thus confirming the theoretical
      modeling of nanochannel-network growth in diamond-type cubic lipid particles. The
      reported structural findings, highlighting that bilayer vesicle membrane packing
      and fusion are required for nanochanneled cubosome particle formation, are
      anticipated to advance the engineering of small lipid NPs with controllable
      channels for biomolecular loading and release.

PMID- 23148666
TI  - Clinical procedure for colon carcinoma tissue sampling directly affects the
      cancer marker-capacity of VEGF family members.
AB  - BACKGROUND: mRNA levels of members of the Vascular Endothelial Growth Factor
      family (VEGF-A, -B, -C, -D, Placental Growth Factor/PlGF) have been investigated
      as tissue-based markers of colon cancer. These studies, which used specimens
      obtained by surgical resection or colonoscopic biopsy, yielded contradictory
      results. We studied the effect of the sampling method on the marker accuracy of
      VEGF family members. METHODS: Comparative RT-qPCR analysis was performed on
      healthy colon and colon carcinoma samples obtained by biopsy (n = 38) or
      resection (n = 39) to measure mRNA expression levels of individual VEGF family
      members. mRNA levels of genes encoding the eicosanoid enzymes cyclooxygenase 2
      (COX2) and 5-lipoxygenase (5-LOX) and of genes encoding the hypoxia markers
      glucose transporter 1 (GLUT-1) and carbonic anhydrase IX (CAIX) were included as
      markers for cellular stress and hypoxia. RESULTS: Expression levels of COX2, 5
      LOX, GLUT-1 and CAIX revealed the occurrence in healthy colon resection samples
      of hypoxic cellular stress and a concurrent increment of basal expression levels
      of VEGF family members. This increment abolished differential expression of VEGF
      B and VEGF-C in matched carcinoma resection samples and created a surgery-induced
      underexpression of VEGF-D. VEGF-A and PlGF showed strong overexpression in
      carcinoma samples regardless of the sampling method. CONCLUSIONS: Sampling
      induced hypoxia in resection samples but not in biopsy samples affects the marker
      reliability of VEGF family members. Therefore, biopsy samples provide a more
      accurate report on VEGF family mRNA levels. Furthermore, this limited expression
      analysis proposes VEGF-A and PlGF as reliable, sampling procedure insensitive
      mRNA-markers for molecular diagnosis of colon cancer.

PMID- 23148667
TI  - The SNP at -592 of human IL-10 gene is associated with serum IL-10 levels and
      increased risk for human papillomavirus cervical lesion development.
AB  - BACKGROUND: Women with Human Papilloma Virus (HPV) persistence are characterized
      by high levels of IL-10 at cervix. We have determined whether polymorphisms of IL
      10 gene promoter might be associated with increased risk of squamous
      intraepithelial cervical lesions (SICL) and whether exist significative
      differences of IL-10 mRNA expression at cervix and systemic and serum IL-10
      protein between SICL cases and non-Cervical Lesions (NCL). METHODS: Peripheral
      blood samples from SICL (n = 204) and NCL (n = 166) were used to detect IL-10
      promoter polymorphisms at loci -592A/C (rs1800872), -819C/T (rs1800871), -1082A/G
      (rs1800896), -1352A/G (rs1800893), by allelic discrimination and to evaluate
      serum IL-10 protein. Cervical epithelial scrapings from NCL and biopsies from
      SICLs were used for HPV-typing and to evaluate IL-10 mRNA expression level. The
      systemic and local IL-10 mRNA expression levels were measured by real time-PCR.
      Genotypic and allelic frequencies of the selected polymorphisms were analyzed by
      logistic regression, adjusting by age and HPV-genotype, to determine the
      association with SICL. RESULTS: No significant differences were found between
      genotype frequencies at loci -819, -1082, and -1352. Individuals carrying at
      least one copy of risk allele A of polymorphism -592 had a two-fold increased
      risk of developing SICL [adjusted odds ratio (OR), 2.02 (95% CI, 1.26-3.25), p =
      0.003], compared to NCL. The IL-10 mRNA expression and serum IL-10 protein, were
      significantly higher in SICL cases (p < 0.01), being higher in patients carrying
      the risk allele A. CONCLUSIONS: The -592 polymorphism is associated with
      increased risk of SICL and can serve as a marker of genetic susceptibility to
      SICL among Mexican women. According to IL-10 levels found in SICL, IL-10 can be
      relevant factor for viral persistence and progression disease.

PMID- 23148668
TI  - Identification of a new cell line permissive to porcine reproductive and
      respiratory syndrome virus infection and replication which is phenotypically
      distinct from MARC-145 cell line.
AB  - BACKGROUND: Airborne transmitted pathogens, such as porcine reproductive and
      respiratory syndrome virus (PRRSV), need to interact with host cells of the
      respiratory tract in order to be able to enter and disseminate in the host
      organism. Pulmonary alveolar macrophages (PAM) and MA104 derived monkey kidney
      MARC-145 cells are known to be permissive to PRRSV infection and replication and
      are the most studied cells in the literature. More recently, new cell lines
      developed to study PRRSV have been genetically modified to make them permissive
      to the virus. The SJPL cell line origin was initially reported to be epithelial
      cells of the respiratory tract of swine. Thus, the goal of this study was to
      determine if SJPL cells could support PRRSV infection and replication in vitro.
      RESULTS: The SJPL cell growth was significantly slower than MARC-145 cell growth.
      The SJPL cells were found to express the CD151 protein but not the CD163 and
      neither the sialoadhesin PRRSV receptors. During the course of the present study,
      the SJPL cells have been reported to be of monkey origin. Nevertheless, SJPL
      cells were found to be permissive to PRRSV infection and replication even if the
      development of the cytopathic effect was delayed compared to PRRSV-infected MARC
      145 cells. Following PRRSV replication, the amount of infectious viral particles
      produced in SJPL and MARC-145 infected cells was similar. The SJPL cells allowed
      the replication of several PRRSV North American strains and were almost efficient
      as MARC-145 cells for virus isolation. Interestingly, PRRSV is 8 to 16 times more
      sensitive to IFNalpha antiviral effect in SJPL cell in comparison to that in MARC
      145 cells. PRRSV induced an increase in IFNbeta mRNA and no up regulation of
      IFNalpha mRNA in both infected cell types. In addition, PRRSV induced an up
      regulation of IFNgamma and TNF-alpha mRNAs only in infected MARC-145 cells.
      CONCLUSIONS: In conclusion, the SJPL cells are permissive to PRRSV. In addition,
      they are phenotypically different from MARC-145 cells and are an additional tool
      that could be used to study PRRSV pathogenesis mechanisms in vitro.

PMID- 23148670
TI  - Iron-amide-sulfide and iron-imide-sulfide clusters: heteroligated core
      environments relevant to the nitrogenase FeMo cofactor.
AB  - Heteroligated cluster cores consisting of weak-field iron, strongly basic
      nitrogen anions, and sulfide are of interest with respect to observed and
      conjectured environments in the FeMo cofactor of nitrogenase. Selective syntheses
      have been developed to achieve such environments with tert-butyl-substituted
      amide and imide core ligands. A number of different routes were employed,
      including nominal ligand substitution and oxidative addition reactions, as well
      as novel transformations involving the combination of different cluster
      precursors. New cluster products include precursor Fe(2)(MU
      NH(t)Bu)(2)[N(SiMe(3))(2)](2) (6), Fe(2)(MU-NH(t)Bu)(2)(MU-S)[N(SiMe(3))(2)](2)
      (7), which has a rare confacial bitetrahedral geometry previously unknown in iron
      chemistry, [Fe(2)(MU-N(t)Bu)(MU-S)Cl(4)](2-) (2), and cuboidal [Fe(4)(MU(3)
      N(t)Bu)(3)(MU(3)-S)Cl(4)](-) (8), [Fe(4)(MU(3)-N(t)Bu)(2)(MU(3)-S)(2)Cl(4)](2-)
      (9), and [Fe(4)(MU(3)-N(t)Bu)(MU(3)-S)(3)Cl(4)](2-) (10), as well as selenide
      substituted derivatives Fe(2)(MU-NH(t)Bu)(2)(MU-Se)[N(SiMe(3))(2)](2) (7-Se) and
      [Fe(4)(MU(3)-N(t)Bu)(MU(3)-Se)(3)Cl(4)](2-) (10-Se). The imide-sulfide clusters
      complete the compositional sets [Fe(2)(MU-N(t)Bu)(n)(MU-S)(2-n)Cl(4)](2-) (n = 0
      2) and [Fe(4)(MU(3)-N(t)Bu)(n)(MU(3)-S)(4-n)Cl(4)](z) (n = 0-4), represented
      previously only by the all-imide and all-sulfide core congeners, and they share
      chemical and physical properties with the parent homoleptic core species. All
      imide-sulfide cores are compositionally stable and show no evidence of core
      ligand exchange over days in solution. Beyond structural differences, the impact
      of mixed core ligation is most evident in redox potentials, which show
      progressive decreases of -435 (for z = 1-/2-) or -385 mV (for z = 2-/3-) for each
      replacement of sulfide by the more potent imide donor, and a corresponding effect
      may be expected for the interstitial heteroligand in the FeMo cofactor. Cluster
      10 presents an [Fe(4)NS(3)] core framework virtually isometric with the
      isostructural [Fe(4)S(3)X] subunit of the FeMo cofactor, thus providing a
      synthetic structural representation for this portion of the cofactor core.

PMID- 23148669
TI  - Development, screening, and analysis of DNA aptamer libraries potentially useful
      for diagnosis and passive immunity of arboviruses.
AB  - BACKGROUND: Nucleic acid aptamers have long demonstrated the capacity to bind
      viral envelope proteins and to inhibit the progression of pathogenic virus
      infections. Here we report on initial efforts to develop and screen DNA aptamers
      against recombinant envelope proteins or synthetic peptides and whole inactivated
      viruses from several virulent arboviruses including Chikungunya, Crimean-Congo
      hemorrhagic fever (CCHF), dengue, tickborne encephalitis and West Nile viruses.
      We also analyzed sequence data and secondary structures for commonalities that
      might reveal consensus binding sites among the various aptamers. Some of the
      highest affinity and most specific aptamers in the down-selected libraries were
      demonstrated to have diagnostic utility in lateral flow chromatographic assays
      and in a fluorescent aptamer-magnetic bead sandwich assay. Some of the reported
      aptamers may also be able to bind viral envelope proteins in vivo and therefore
      may have antiviral potential in passive immunity or prophylactic applications.
      RESULTS: Several arbovirus DNA aptamer sequences emerged multiple times in the
      various down selected aptamer libraries thereby suggesting some consensus
      sequences for binding arbovirus envelope proteins. Screening of aptamers by
      enzyme-linked aptamer sorbent assay (ELASA) was useful for ranking relative
      aptamer affinities against their cognate viral targets. Additional study of the
      aptamer sequences and secondary structures of top-ranked anti-arboviral aptamers
      suggest potential virus binding motifs exist within some of the key aptamers and
      are highlighted in the supplemental figures for this article. One sequence
      segment (ACGGGTCCGGACA) emerged 60 times in the anti-CCHF aptamer library, but
      nowhere else in the anti-arbovirus library and only a few other times in a larger
      library of aptamers known to bind bacteria and rickettsia or other targets.
      Diagnostic utility of some of the aptamers for arbovirus detection in lateral
      flow chromatographic assays and a fluorescent sandwich assay on the surface of
      magnetic microbeads is also demonstrated. CONCLUSIONS: This article catalogues
      numerous DNA aptamer sequences which can bind various important pathogenic
      arboviruses and have, in some cases, already demonstrated diagnostic potential.
      These aptamer sequences are proprietary, patent-pending, and partially
      characterized. Therefore, they are offered to the scientific community for
      potential research use in diagnostic assays, biosensor applications or for
      possible passive immunity and prophylaxis against pathogenic viruses.

PMID- 23148671
TI  - Tea creaming in nonfermented teas from Camellia sinensis and Ilex vomitoria.
AB  - Tea creaming is the development of a cloudy or hazy appearance in tea and ready
      to-drink tea products on cooling and is highly undesirable in the tea beverage
      industry. Commonly associated with fermented black or oolong teas, the objective
      of this study was to investigate the physicochemical mechanism of the formation
      of tea cream in nonfermented green tea (Camellia sinensis) and a caffeine
      containing botanical tea from yaupon holly (Ilex vomitoria) that is free of
      catechin-based polyphenolics. Four tea-creaming activators (phenolics, soluble
      protein, caffeine, and metal ions) were added to tea infusions as well as
      decaffeinated teas created by chloroform extraction. Tea-creaming activators
      increased the weight and turbidity of both teas with the exception of soluble
      protein addition (as bovine serum albumin) to green tea, whereas the greatest
      increase in turbidity occurred with the addition of metal ions in green tea. Tea
      creaming was equally developed at three incubation temperatures (4, 25, and 40 
      degrees C) in both teas, but tea-creaming compositions in each tea were different
      at the incubating temperatures. The antioxidant capacity of each tea was lowered
      after creaming due to the loss of antioxidants that participated in tea cream
      formation.

PMID- 23148672
TI  - Bioactivation of 2-(alkylthio)-1,3,4-thiadiazoles and 2-(alkylthio)-1,3
      benzothiazoles.
AB  - Certain functional groups/structural motifs are known to generate chemically
      reactive metabolites that can covalently modify essential cellular macromolecules
      and, therefore, have the potential to disrupt biological function and elicit
      idiosyncratic adverse drug reactions. In this report, we describe the
      bioactivation of 5-substituted 2-(alkylthio)-1,3,4-thiadiazoles and 2-(alkylthio)
      1,3-benzothiazoles, which can be added to the growing list of structural alerts.
      When 5-substituted 2-(methylthio)-1,3,4-thiadiazoles and 2-(methylthio)-1,3
      benzothiazole were incubated with pooled human liver microsomes in the presence
      of NADPH and GSH, unusual GSH adducts were formed. Characterization of these GSH
      adducts by high-resolution mass spectrometry indicated the replacement of the
      methylthio- group by GSH, and NMR experiments ascertained the proposed
      structures. On the basis of the metabolic profile change in incubation samples
      with/without GSH, we proposed that the GSH adduct formation involved two steps:
      (1) enzymatic oxidation of the alkylthio- group to form sulfoxide and sulfone and
      (2) nucleophilic displacement of the formed sulfoxide and sulfone by GSH. The
      proposed mechanism was confirmed by the formation of the same GSH adduct from the
      incubation of synthetically prepared sulfoxide and sulfone compounds in buffer.
      We found the sulfur oxidation step was significantly inhibited (80-100%) by
      preincubation with 1-aminobenzotriazole but was much less affected by
      thermoinactivation (0-45%), suggesting that the sulfoxidation step is primarily
      catalyzed by cytochrome P450s and not by flavin monooxygenases. We also
      investigated the presence of this bioactivation pathway in more than a dozen
      compounds containing 2-(alkylthio)-1,3,4-thiadiazole and 2-(alkylthio)-1,3
      benzothiazoles. The common GSH adduct formation pathway demonstrated by current
      studies raises a new structural alert and potential liability in drug safety when
      2-alkylthio derivatives of 1,3-benzothiazoles and 1,3,4-thiadiazoles are
      incorporated in drug design.

PMID- 23148674
TI  - Trigohowilols A-G, degraded diterpenoids from the stems of Trigonostemon howii.
AB  - Two new degraded diterpenoids, trigohowilols A (1) and B (2), four new
      heterodimers, trigohowilols C-F (3-6), one new homodimer, trigohowilol G (7), and
      three known degraded diterpenoids (8-10) were isolated from the methanol extract
      of the stems of Trigonostemon howii. Compounds 1-7 were evaluated for their
      cytotoxic activity against five human tumor cell lines by an MTT assay, and
      trigohowilols E (5) and F (6) exhibited inhibitory activity with IC50 values
      ranging from 2.33 to 12.57 MUM. Moreover, compounds 1-6 showed weak antimicrobial
      activities (MIC values: 6.25-25 MUg/mL) against Staphylococcus aureus,
      Pseudomonas aeruginosa, MRSA 92(#), and MRSA 98(#) using a 2-fold dilution
      method. 

PMID- 23148675
TI  - Positron emission tomography in malignancies of the liver, pancreas and biliary
      tract - indications and potential pitfalls.
AB  - Abstract Malignancies of the hepato-pancreatico-biliary (HPB) system are
      relatively common and generally characterized by a dismal prognosis. Positron
      emission tomography (PET) is a functional imaging technique that has emerged as
      an important modality in oncological decision-making. The principal
      radiopharmaceutical in PET imaging is the glucose analog (18)F
      fluorodeoxyglucose, which is able to detect altered glucose metabolism in
      malignant tissue. PET is typically used in conjunction with computed tomography
      (CT), and previous studies have supported several uses of PET/CT in HPB
      malignancies, including staging, differential diagnostics and monitoring of
      treatment response and progress of disease. A review of PET/CT in the context of
      HPB malignancies will be presented, including indications and potential pitfalls.

PMID- 23148676
TI  - Silicification of genipin-cross-linked polypeptide hydrogels toward biohybrid
      materials and mesoporous oxides.
AB  - A simple and versatile approach is proposed to use cross-linked polypeptide
      hydrogels as templates for silica mineralization, allowing the synthesis of
      polypeptide-silica hybrid hydrogels and mesoporous silica (meso-SiO(2)) by
      subsequent calcination. The experimental data revealed that the cross-linked
      polypeptide hydrogels comprised of interconnected, membranous network served as
      templates for the high-fidelity transcription of silica replicas spanning from
      nanoscale to microscale, resulting in hybrid network comprised of interpenetrated
      polypeptide nanodomains and silica. The mechanical properties of these as
      prepared polypeptide-silica hybrid hydrogels were found to vary with polypeptide
      chain length and composition. The synergy between cross-link, hydrophobic
      interaction, and silica deposition can lead to the enhancement of their
      mechanical properties. The polypeptide-silica hybrid hydrogel with polypeptide
      and silica content as low as 1.1 wt% can achieve 114 kN/m(2) of compressive
      strength. By removing the polypeptide nanodomains, mesoporous silicas with
      average pore sizes ranged between 2 nm and 6 nm can be obtained, depending on
      polypeptide chain length and composition. The polypeptide-silica hybrid hydrogels
      demonstrated good cell compatibility and can support cell
      attachment/proliferation. With the versatility of polymer chemistry and
      feasibility of amine-catalyzed sol-gel chemistry, the present method is facile
      for the synthesis of green nanocomposites and biomaterials.

PMID- 23148677
TI  - A Rasch model analysis of NEO PI-R fearless dominance and impulsive antisociality
      scales.
AB  - This study reports a Rasch model analysis of psychopathic trait measures of
      fearless dominance and impulsive antisociality (Witt et al., 2010). Through use
      of secondary data analysis (N = 200), these scales were evaluated to determine
      whether they provided effective dimensional measurement evidenced by a) one
      dimensional structure, b) broad targeting of the latent dimensions, and c)
      invariance across men and women. Only fearless dominance achieved an invariant
      one-dimensional structure after slight modification. Both fearless dominance and
      impulsive antisociality had a restricted range in targeting of the latent trait
      dimensions. With one exception, scale items did not exhibit differential item
      functioning across men and women. Implications of the results are discussed
      within the context of Rasch analysis and the conceptualization of psychopathy.

PMID- 23148678
TI  - Clinical utility of serum reproductive hormones for the early diagnosis of
      ectopic pregnancy in the first trimester.
AB  - AIM: A tubal ectopic pregnancy (EP) in the first trimester remains a major life
      threatening complication for the mother. We aim to determine whether serum
      reproductive hormones may be clinically useful in the early identification of a
      tubal EP. METHODS: A total of 109 age-matched patients with a serum beta-human
      chorionic gonadotropin (beta-hCG) concentration <2000 IU/L were enrolled,
      including 68 patients with a tubal EP, 22 with a viable intrauterine pregnancy
      (vIUP) and 19 with a non-viable intrauterine pregnancy (nIUP). Serum was
      collected during the first trimester of pregnancy and assayed for beta-hCG,
      follicle-stimulating hormone (FSH), luteinizing hormone (LH), testosterone (TE),
      progesterone (P), estradiol (E2) and prolactin (PRL) by using automated
      electrochemiluminescence immunoassays. RESULTS: Patients with an EP had
      significantly lower levels of daily beta-hCG variation (Deltabeta-hCG/day), P and
      E2, and significantly higher levels of LH and FSH than IUP patients (P<0.05). As
      an EP diagnostic marker, progesterone demonstrated a sensitivity of 100% at the
      cutoff of 86.01 nmol/L. The combination of E2 with Deltabeta-hCG/day reached a
      specificity of 100% for EP evaluation. To identify non-viable pregnancies
      (including EPs and nIUPs), progesterone demonstrated a sensitivity of 95.40% and
      a specificity of 90.91% at the cutoff of 63.2 nmol/L; the diagnostic power of the
      receiver operating curve was 0.9702. CONCLUSIONS: A combination of Deltabeta
      hCG/day, P and E2 may help distinguish EPs and nIUPs from vIUPs, facilitating
      earlier diagnosis and the timely implementation of medical treatment to prevent
      tubal rupture.

PMID- 23148679
TI  - Direct intermolecular aniline ortho-arylation via benzyne intermediates.
AB  - A method for direct, transition-metal-free ortho-arylation of anilines by aryl
      chlorides, bromides, fluorides, and triflates has been developed. This
      methodology provides the most direct approach to 2-arylanilines since no
      protecting or directing groups on nitrogen are required. The arylation is
      functional-group tolerant, with alkene, ether, trifluoromethyl, dimethylamino,
      carbonyl, chloro, and cyano functionalities tolerated. Phenylation of enantiopure
      binaphthyldiamine affords a product with >99% ee.

PMID- 23148680
TI  - Virial equation of state of water based on Wertheim's association theory.
AB  - Wertheim's multidensity formalism for pairwise additive molecular interaction is
      extended to handle nonadditive contributions and is applied to formulate an
      equation of state (WEOS) for the Gaussian-charge polarizable model (GCPM) of
      water, with cluster integrals appearing in the theory calculated via the Mayer
      sampling Monte Carlo method. At both sub- and supercritical temperatures, the
      equation of state of GCPM water obtained from WEOS converges well to Monte Carlo
      simulation data, and performs significantly better than the conventional virial
      treatment (VEOS). The critical temperature for GCPM water using a fourth-order
      WEOS is given to within 1.3% of the established value, compared to a 17% error
      shown by fifth-order VEOS; as seen in previous applications, the critical density
      obtained from both VEOS and WEOS significantly underestimates the true critical
      density for GCPM water. Examination of the magnitudes of the computed cluster
      diagrams at the critical density finds that negligible contributions are made by
      clusters in which a water molecule has both of its hydrogens involved in
      association interactions.

PMID- 23148682
TI  - NaHSO4-SiO2 as an efficient and chemoselective catalyst, for the synthesis of
      acylal from aldehydes under, solvent-free conditions.
AB  - BACKGROUND: Structurally diverse aldehydes are successfully converted into
      acylals (1,1-diacetates) with acetic anhydride using NaHSO4-SiO2 as a mild,
      convenient and inexpensive catalyst under solvent-free conditions. The noteworthy
      features of the present system are shorter reaction times, and mild and solvent
      free conditions. Furthermore, it offers chemoselective protection of aldehydes.
      RESULTS: Both aromatic and aliphatic aldehydes reacts smoothly with acetic
      anhydride in presence of silica supported sodium hydrogen sulphate to afford the
      corresponding 1,1-diacetates in good to excellent yields. We studied competitive
      reactions for the acylation of aldehydes in the presence of ketones using silica
      supported sodium hydrogen sulphate as a catalyst. Using this catalytic system,
      the highly selective conversion of an aldehyde in the presence of ketone was
      observed. CONCLUSIONS: NaHSO4-SiO2 is a chemoselective and highly efficient
      catalyst for acylal formation from aldehydes. The advantages of this methodology
      over the reported methods is the availability of the starting materials,
      simplicity of acylation procedure, a clean work-up, a short reaction time, high
      yields and reusability.

PMID- 23148681
TI  - IL-32 and IL-17 interact and have the potential to aggravate osteoclastogenesis
      in rheumatoid arthritis.
AB  - INTRODUCTION: Interleukin (IL)-32 and IL-17 play critical roles in pro
      inflammatory responses and are highly expressed in the synovium of patients with
      rheumatoid arthritis (RA). We investigated the relations between these two
      cytokines (IL-17 and IL-32) for their ability to induce each other and to
      stimulate osteoclasts in RA fibroblast-like synoviocytes (FLSs) and T cells.
      METHODS: FLSs were isolated through surgical synovectomy obtained from patients
      with RA or osteoarthritis (OA). Real-time PCR were performed to evaluate the
      expression of IL-32, IL-17 and osteoclast-related genes. Immunohistochemical
      staining and tartrate-resistant acid phosphatase (TRAP) staining were performed
      to determine the distribution of inflammatory cytokines and the presence of
      osteoclastogenesis. RESULTS: IL-17 induced the expression of IL-32 in the FLSs
      from RA patients, as assessed by microarray. IL-32 production was increased by IL
      17. IL-32 in the FLSs from RA patients induced the production of IL-17 in CD4+ T
      cells. IL-32 and IL-17 were colocalized near TRAP-positive areas in joint
      specimens. IL-17 and IL-32 synergistically induced the differentiation of
      osteoclasts, as demonstrated by the expression of osteoclast-related genes. IL-32
      and IL-17 also could induce resorption by osteoclasts in a RANKL-dependent
      manner. CONCLUSIONS: IL-17 affected the expression of IL-32 in FLSs of RA
      patients and IL-32 induced the production of IL-17 in CD4+ T cells. Both IL-17
      and IL-32 cytokines can reciprocally influence each other's production and
      amplify the function of osteoclastogenesis in the in RA synovium. Separately, IL
      17 and IL-32 each stimulated osteoclastogenesis without RANKL. Together, the two
      cytokines synergistically amplified the differentiation of osteoclasts,
      independent of RANKL stimulation.

PMID- 23148683
TI  - A gene-networked gel matrix-supported lipid bilayer as a synthetic nucleus
      system.
AB  - A spheroidal transgene-networked gel matrix was designed as a synthetic nucleus
      system. It was spheroidically manufactured using both advanced lithography and
      DNA nanotechnology. Stable Aqueorea coerulescens green fluorescent protein
      (AcGFP)-encoding gene cross-networks have been optimized in various parameters:
      the number of gene-networked gel (G-net-gel) spheroids, the concentration of a
      AcGFP plasmid in the scaffold, and the molar ratio between the X-DNA building
      blocks and the gene. It was then assessed that 800 units of the gene networked
      gel matrix at a 4000:1 molar ratio of X-DNA blocks and AcGFP gene components
      accomplished 20-fold enhanced in vitro protein expression efficiency for 36 h.
      Furthermore, once with lipid capping, it reproduced the natural nucleus system,
      demonstrating the 2-fold increased levels of messenger RNAs (mRNAs) relative to
      solution phase vectors.

PMID- 23148684
TI  - Unique functions of CHK1 and WEE1 underlie synergistic anti-tumor activity upon
      pharmacologic inhibition.
AB  - BACKGROUND: Inhibition of kinases involved in the DNA damage response sensitizes
      cells to genotoxic agents by abrogating checkpoint-induced cell cycle arrest.
      CHK1 and WEE1 act in a pathway upstream of CDK1 to inhibit cell cycle progression
      in response to damaged DNA. Therapeutic targeting of either CHK1 or WEE1, in
      combination with chemotherapy, is under clinical evaluation. These studies
      examine the overlap and potential for synergy when CHK1 and WEE1 are inhibited in
      cancer cell models. METHODS: Small molecules MK-8776 and MK-1775 were used to
      selectively and potently inhibit CHK1 and WEE1, respectively. RESULTS: In vitro,
      the combination of MK-8776 and MK-1775 induces up to 50-fold more DNA damage than
      either MK-8776 or MK-1775 alone at a fixed concentration. This requires aberrant
      cyclin-dependent kinase activity but does not appear to be dependent on p53
      status alone. Furthermore, DNA damage takes place primarily in S-phase cells,
      implying disrupted DNA replication. When dosed together, the combination of MK
      8776 and MK-1775 induced more intense and more durable DNA damage as well as anti
      tumor efficacy than either MK-8776 or MK-1775 dosed alone. DNA damage induced by
      the combination was detected in up to 40% of cells in a treated xenograft tumor
      model. CONCLUSIONS: These results highlight the roles of WEE1 and CHK1 in
      maintaining genomic integrity. Importantly, the strong synergy observed upon
      inhibition of both kinases suggests unique yet complimentary anti-tumor effects
      of WEE1 and CHK1 inhibition. This demonstration of DNA double strand breaks in
      the absence of a DNA damaging chemotherapeutic provides preclinical rationale for
      combining WEE1 and CHK1 inhibitors as a cancer treatment regimen.

PMID- 23148685
TI  - Validation of reference genes from Eucalyptus spp. under different stress
      conditions.
AB  - BACKGROUND: The genus Eucalyptus consists of approximately 600 species and
      subspecies and has a physiological plasticity that allows some species to
      propagate in different regions of the world. Eucalyptus is a major source of
      cellulose for paper manufacturing, and its cultivation is limited by weather
      conditions, particularly water stress and low temperatures. Gene expression
      studies using quantitative reverse transcription polymerase chain reaction (qPCR)
      require reference genes, which must have stable expression to facilitate the
      comparison of the results from analyses using different species, tissues, and
      treatments. Such studies have been limited in eucalyptus. RESULTS: Eucalyptus
      globulus Labill, Eucalyptus urograndis (hybrid from Eucalyptus urophylla S.T.
      Blake X Eucalyptus grandis Hill ex-Maiden) and E. uroglobulus (hybrid from E.
      urograndis X E. globulus) were subjected to different treatments, including water
      deficiency and stress recovery, low temperatures, presence or absence of light,
      and their respective controls. Except for treatment with light, which examined
      the seedling hypocotyl or apical portion of the stem, the expression analyses
      were conducted in the apical and basal parts of the stem. To select the best pair
      of genes, the bioinformatics tools GeNorm and NormFinder were compared.
      Comprehensive analyses that did not differentiate between species, treatments, or
      tissue types, showed that IDH (isocitrate dehydrogenase), SAND (SAND protein),
      ACT (actin), and A-Tub (alpha-tubulin) genes were the most stable. IDH was the
      most stable gene in all of the treatments. CONCLUSION: Comparing these results
      with those of other studies on eucalyptus, we concluded that five genes are
      stable in different species and experimental conditions: IDH, SAND, ACT, A-Tub,
      and UBQ (ubiquitin). It is usually recommended a minimum of two reference genes
      is expression analysis; therefore, we propose that IDH and two others genes among
      the five identified genes in this study should be used as reference genes for a
      wide range of conditions in eucalyptus.

PMID- 23148688
TI  - Room temperature metalation of 2H-TPP monolayer on iron and nickel surfaces by
      picking up substrate metal atoms.
AB  - Here, it is demonstrated, using high-resolution X-ray spectroscopy and density
      functional theory calculations, that 2H-tetraphenyl porphyrins metalate at room
      temperature by incorporating a surface metal atom when a (sub)monolayer is
      deposited on 3d magnetic substrates, such as Fe(110) and Ni(111). The
      calculations demonstrate that the redox metalation reaction would be exothermic
      when occurring on a Ni(111) substrate with an energy gain of 0.89 eV upon
      embedding a Ni adatom in the macrocycle. This is a novel way to form, via
      chemical modification and supramolecular engineering, 3d-metal-organic networks
      on magnetic substrates with an intimate bond between the macrocycle molecular
      metal ion and the substrate atoms. The achievement of a complete metalation by Fe
      and Ni can be regarded as a test case for successful preparation of spintronic
      devices by means of molecular-based magnets and inorganic magnetic substrates.

PMID- 23148687
TI  - The Schistosoma mansoni phylome: using evolutionary genomics to gain insight into
      a parasite's biology.
AB  - BACKGROUND: Schistosoma mansoni is one of the causative agents of
      schistosomiasis, a neglected tropical disease that affects about 237 million
      people worldwide. Despite recent efforts, we still lack a general understanding
      of the relevant host-parasite interactions, and the possible treatments are
      limited by the emergence of resistant strains and the absence of a vaccine. The
      S. mansoni genome was completely sequenced and still under continuous annotation.
      Nevertheless, more than 45% of the encoded proteins remain without experimental
      characterization or even functional prediction. To improve our knowledge
      regarding the biology of this parasite, we conducted a proteome-wide evolutionary
      analysis to provide a broad view of the S. mansoni's proteome evolution and to
      improve its functional annotation. RESULTS: Using a phylogenomic approach, we
      reconstructed the S. mansoni phylome, which comprises the evolutionary histories
      of all parasite proteins and their homologs across 12 other organisms. The
      analysis of a total of 7,964 phylogenies allowed a deeper understanding of
      genomic complexity and evolutionary adaptations to a parasitic lifestyle. In
      particular, the identification of lineage-specific gene duplications pointed to
      the diversification of several protein families that are relevant for host
      parasite interaction, including proteases, tetraspanins, fucosyltransferases,
      venom allergen-like proteins, and tegumental-allergen-like proteins. In addition
      to the evolutionary knowledge, the phylome data enabled us to automatically re
      annotate 3,451 proteins through a phylogenetic-based approach rather than solely
      sequence similarity searches. To allow further exploitation of this valuable
      data, all information has been made available at PhylomeDB
      (http://www.phylomedb.org). CONCLUSIONS: In this study, we used an evolutionary
      approach to assess S. mansoni parasite biology, improve genome/proteome
      functional annotation, and provide insights into host-parasite interactions.
      Taking advantage of a proteome-wide perspective rather than focusing on
      individual proteins, we identified that this parasite has experienced specific
      gene duplication events, particularly affecting genes that are potentially
      related to the parasitic lifestyle. These innovations may be related to the
      mechanisms that protect S. mansoni against host immune responses being important
      adaptations for the parasite survival in a potentially hostile environment.
      Continuing this work, a comparative analysis involving genomic, transcriptomic,
      and proteomic data from other helminth parasites, other parasites, and vectors
      will supply more information regarding parasite's biology as well as host
      parasite interactions.

PMID- 23148690
TI  - Calix[4]arenes of aluminum and gallium with benzimidazolyl ligands: steric
      control of the conformation via substitution on the ligand.
AB  - Complexes [bzimAlR(2)](4) [bzim = benzimidazolate; R = Et (2), (i)Bu (3)],
      [mbzimAlR(2)](4) [mbzim = 2-methylbenzimidazolate; R = Et (6), (i)Bu (7)],
      [dmbzimAlR(2)](4) [dmbzim = 5,6-dimethylbenzimidazolate; R = Me (9), Et (10),
      (i)Bu (11)], and [tmbzimAlR(2)](4) [tmbzim = 2,5,6-trimethylbenzimidazolate; R =
      Me (12), Et (13), (i)Bu (14)] have been prepared via alkane elimination and
      coordinative self-assembly upon the reaction of benzimidazole ligands with
      aluminum alkyls in benzene, toluene, or xylene. Characterization of the complexes
      was achieved by spectroscopic methods, microanalysis, and X-ray crystallography
      of 2, 7, 10, 11, 13, and 14. The complexes reported herein and the aluminum and
      gallium analogues 1, 4, 5, and 8 reported in a previous paper (1)  are
      predominantly tetranuclear aggregates related to calix[4]arenes in which the
      benzimidazolyl ligands bind two metal atoms in a eta(1):eta(1) fashion. X-ray
      crystallography demonstrates that modulation of the conformation adopted by these
      metallacalix[4]arenes is achieved by proper substitution on the C atom at the 2
      position of the benzimidazolyl ligand. An H substituent for 1, 2, 4, 10, and 11
      favors a chair conformation with a small cavity and approximate C(2h) symmetry,
      while a CH(3) substituent for 5, 7, 8, 13, and 14 introduces enough repulsion to
      switch the conformation to a 1,3-alternate or double cone with a concomitant
      larger cavity and approximate C(2v) symmetry.

PMID- 23148689
TI  - Structural and molecular basis of interaction of HCV non-structural protein 5A
      with human casein kinase 1alpha and PKR.
AB  - BACKGROUND: Interaction of non-structural protein 5A (NS5A) of Hepatitis C virus
      (HCV) with human kinases namely, casein kinase 1alpha (ck1alpha) and protein
      kinase R (PKR) have different functional implications such as regulation of viral
      replication and evasion of interferon induced immune response respectively.
      Understanding the structural and molecular basis of interactions of the viral
      protein with two different human kinases can be useful in developing strategies
      for treatment against HCV. RESULTS: Serine 232 of NS5A is known to be
      phosphorylated by human ck1alpha. A structural model of NS5A peptide containing
      phosphoacceptor residue Serine 232 bound to ck1alpha has been generated using the
      known 3-D structures of kinase-peptide complexes. The substrate interacting
      residues in ck1alpha has been identified from the model and these are found to be
      conserved well in the ck1 family. ck1alpha - substrate peptide complex has also
      been used to understand the structural basis of association between ck1alpha and
      its other viral stress induced substrate, tumour suppressor p53 transactivation
      domain which has a crystal structure available.Interaction of NS5A with another
      human kinase PKR is primarily genotype specific. NS5A from genotype 1b has been
      shown to interact and inhibit PKR whereas NS5A from genotype 2a/3a are unable to
      bind and inhibit PKR efficiently. This is one of the main reasons for the varied
      response to interferon therapy in HCV patients across different genotypes. Using
      PKR crystal structure, sequence alignment and evolutionary trace analysis some of
      the critical residues responsible for the interaction of NS5A 1b with PKR have
      been identified. CONCLUSIONS: The substrate interacting residues in ck1alpha have
      been identified using the structural model of kinase - substrate peptide. The PKR
      interacting NS5A 1b residues have also been predicted using PKR crystal
      structure, NS5A sequence analysis along with known experimental results.
      Functional significance and nature of interaction of interferon sensitivity
      determining region and variable region 3 of NS5A in different genotypes with PKR
      which was experimentally shown are also supported by the findings of evolutionary
      trace analysis. Designing inhibitors to prevent this interaction could enable the
      HCV genotype 1 infected patients respond well to interferon therapy.

PMID- 23148691
TI  - Role of specific interfacial area in controlling properties of immiscible blends
      of biodegradable polylactide and poly[(butylene succinate)-co-adipate].
AB  - Binary blends of two biodegradable polymers: polylactide (PLA), which has high
      modulus and strength but is brittle, and poly[(butylene succinate)-co-adipate]
      (PBSA), which is flexible and tough, were prepared through batch melt mixing. The
      PLA/PBSA compositions were 100/0, 90/10, 70/30, 60/40, 50/50, 40/60, 30/70,
      10/90, and 0/100. Fourier-transform infrared measurements revealed the absence of
      any chemical interaction between the two polymers, resulting in a phase-separated
      morphology as shown by scanning electron microscopy (SEM). SEM micrographs showed
      that PLA-rich blends had smaller droplet sizes when compared to the PBSA-rich
      blends, which got smaller with the reduction in PBSA content due to the
      differences in their melt viscosities. The interfacial area of PBSA droplets per
      unit volume of the blend reached a maximum in the 70PLA/30PBSA blend. Thermal
      stability and mechanical properties were not only affected by the composition of
      the blend, but also by the interfacial area between the two polymers. Through
      differential scanning calorimetry, it was shown that molten PBSA enhanced
      crystallization of PLA while the stiff PLA hindered cold crystallization of PBSA.
      Optimal synergies of properties between the two polymers were found in the
      70PLA/30PBSA blend because of the maximum specific interfacial area of the PBSA
      droplets.

PMID- 23148693
TI  - Treatment of human muscle cells with popular dietary supplements increase
      mitochondrial function and metabolic rate.
AB  - BACKGROUND: Obesity is a common pathology with increasing incidence, and is
      associated with increased mortality and healthcare costs. Several treatment
      options for obesity are currently available ranging from behavioral modifications
      to pharmaceutical agents. Many popular dietary supplements claim to enhance
      weight loss by acting as metabolic stimulators, however direct tests of their
      effect on metabolism have not been performed. PURPOSE: This work identified the
      effects popular dietary supplements on metabolic rate and mitochondrial
      biosynthesis in human skeletal muscle cells. METHODS: Human rhabdomyosarcoma
      cells were treated with popular dietary supplements at varied doses for 24 hours.
      Peroxisome proliferator-activated receptor coactivator 1 alpha (PGC-1alpha), an
      important stimulator of mitochondrial biosynthesis, was quantified using
      quantitative reverse transcriptase polymerase chain reaction (qRT-PCR).
      Mitochondrial content was measured using flow cytometry confirmed with confocal
      microscopy. Glycolytic metabolism was quantified by measuring extracellular
      acidification rate (ECAR) and oxidative metabolism was quantified by measuring
      oxygen consumption rate (OCR). Total relative metabolism was quantified using WST
      1 end point assay. RESULTS: Treatment of human rhabdomyosarcoma cells with
      dietary supplements OxyElite Pro (OEP) or Cellucore HD (CHD) induced PGC-1alpha
      leading to significantly increased mitochondrial content. Glycolytic and
      oxidative capacities were also significantly increased following treatment with
      OEP or CHD. CONCLUSION: This is the first work to identify metabolic adaptations
      in muscle cells following treatment with popular dietary supplements including
      enhanced mitochondrial biosynthesis, and glycolytic, oxidative and total
      metabolism.

PMID- 23148692
TI  - Histone demethylase GASC1--a potential prognostic and predictive marker in
      invasive breast cancer.
AB  - BACKGROUND: The histone demethylase GASC1 (JMJD2C) is an epigenetic factor
      suspected of involvement in development of different cancers, including breast
      cancer. It is thought to be overexpressed in the more aggressive breast cancer
      types based on mRNA expression studies on cell lines and meta analysis of human
      breast cancer sets. This study aimed to evaluate the prognostic and predictive
      value of GASC1 for women with invasive breast cancer. METHODS: All the 355 cases
      were selected from a cohort enrolled in the Kuopio Breast Cancer Project between
      April 1990 and December 1995. The expression of GASC1 was studied by
      immunohistochemistry (IHC) on tissue microarrays. Additionally relative GASC1
      mRNA expression was measured from available 57 cases. RESULTS: In our material,
      56% of the cases were GASC1 negative and 44% positive in IHC staining. Women with
      GASC1 negative tumors had two years shorter breast cancer specific survival and
      time to relapse than the women with GASC1 positive tumors (p=0.017 and p=0.034
      respectively). The majority of GASC1 negative tumors were ductal cases (72%) of
      higher histological grade (84% of grade II and III altogether). When we evaluated
      estrogen receptor negative and progesterone receptor negative cases separately,
      there was 2 times more GASC1 negative than GASC1 positive tumors in each group
      (chi2, p= 0.033 and 0.001 respectively). In the HER2 positive cases, there was 3
      times more GASC1 negative cases than GASC1 positives (chi2, p= 0.029). Patients
      treated with radiotherapy (n=206) and hormonal treatment (n=62) had better breast
      cancer specific survival, when they were GASC1 positive (Cox regression: HR=0.49,
      p=0.007 and HR=0.33, p=0.015, respectively). The expression of GASC1 mRNA was in
      agreement with the protein analysis. CONCLUSIONS: This study indicates that the
      GASC1 is both a prognostic and a predictive factor for women with invasive breast
      cancer. GASC1 negativity is associated with tumors of more aggressive
      histopathological types (ductal type, grade II and III, ER negative, PR
      negative). Patients with GASC1 positive tumors have better breast cancer specific
      survival and respond better to radiotherapy and hormonal treatment.

PMID- 23148694
TI  - Systemic thromboembolism after anti-cancer chemotherapy in a woman with ovarian
      germ cell tumor.
AB  - A high cure rate of ovarian germ cell tumors was achieved by establishment of a
      cisplatin-containing regimen. We encountered a rare case of a 33-year-old,
      nulligravida Japanese woman with systemic thromboembolism following anti-cancer
      chemotherapy with cisplatin, etoposide, and bleomycin in ovarian germ cell tumor.
      She suffered from brain infarction, multiple embolisms in the bilateral pulmonary
      artery and pelvic vein, and a broad range of deep vein thromboses in the right
      extremities vein. When thrombosis is detected during anti-cancer chemotherapy, we
      must investigate whether the presence of thrombosis is systemic or local.

PMID- 23148697
TI  - Chemotherapy administration: modelling the costs of alternative protocols.
AB  - BACKGROUND AND OBJECTIVE: The increasing cost of chemotherapy is placing greater
      pressures on limited healthcare budgets. A potentially important, but often
      overlooked, aspect of chemotherapy is the cost associated with administration.
      This study aims to develop a better understanding of these costs, and in doing
      so, develop a model to estimate the comparative cost of administering alternative
      chemotherapy protocols for economic evaluation or local decision making. METHODS:
      We identified the potential tasks and choices related to administering
      intravenous chemotherapy, grouped tasks according to anticipated resource use,
      and allocated costs to each task using data from an evidence-based collection of
      cancer protocols or from primary data collection. The resources were costed from
      a healthcare system perspective using standard data sources within Australia. The
      model was applied to alternative protocols used in the treatment of three
      different cancers: locally advanced and metastatic non-small-cell lung cancer,
      adjuvant colorectal cancer and adjuvant breast cancer. RESULTS: For the three
      cancer types examined, the cost of completed administration ranged from 1274
      Australian dollars ($A) to $A3015 (year 2009 values) for 13 different protocols
      potentially used for the initial treatment of locally advanced and metastatic non
      small-cell lung cancer; $A5175-8445 for seven protocols for adjuvant colorectal
      cancer treatment; and $A1494-4074 for seven protocols for adjuvant breast cancer
      treatment. CONCLUSIONS: The results are of practical significance to those
      undertaking economic evaluations and to decision makers who use this information
      within the area of chemotherapy. The examples used suggest that administration
      costs per visit varied inversely with the number of visits. The results provide
      information where little has previously been available and may allow decisions
      about costs and resource allocation to be made with more certainty. Although our
      model uses costs from the public health system within an Australian state (New
      South Wales), it can be adapted for use in other jurisdictions.

PMID- 23148698
TI  - Estimating the contributions of associations and recoding in the Implicit
      Association Test: the ReAL model for the IAT.
AB  - We introduce the ReAL model for the Implicit Association Test (IAT), a
      multinomial processing tree model that allows one to mathematically separate the
      contributions of attitude-based evaluative associations and recoding processes in
      a specific IAT. The ReAL model explains the observed pattern of erroneous and
      correct responses in the IAT via 3 underlying processes: recoding of target and
      attribute categories into a binary representation in the compatible block (Re),
      evaluative associations of the target categories (A), and label-based
      identification of the response that is assigned to the respective nominal
      category (L). In 7 validation studies, using an adaptive response deadline
      procedure in order to increase the amount of erroneous responses in the IAT, we
      demonstrated that the ReAL model fits IAT data and that the model parameters vary
      independently in response to corresponding experimental manipulations. Further
      studies yielded evidence for the specific predictive validity of the model
      parameters in the domain of consumer behavior. The ReAL model allows one to
      disentangle different sources of IAT effects where global effect measures based
      on response times lead to equivocal interpretations. Possible applications and
      implications for future IAT research are discussed.

PMID- 23148699
TI  - It is time to plan further researches on altered nutrient-sensing in irritable
      bowel syndrome.

PMID- 23148700
TI  - Facile preparation of bioactive seco-guaianolides and guaianolides from Artemisia
      gorgonum and evaluation of their phytotoxicity.
AB  - Commercially available santonin was used to synthesize seven sesquiterpene
      lactones using a facile strategy that involved a high-yielding photochemical
      reaction. Three natural products from Artemisia gorgonum were synthesized in good
      yields, and in the case of two compounds, absolute configurations were determined
      from X-ray quality crystals. The structures previously reported for these
      compounds were revised. Sesquiterpene lactones were tested using the etiolated
      wheat coleoptile bioassay, and the most active compounds were assayed in standard
      target species. seco-Guaianolide (4) showed higher phytotoxic activities than the
      known herbicide Logran. This high activity could be due to the presence of a
      cyclopentenedione ring. These results suggest that compound 4 should be involved
      in defense of A. gorgorum, displaying a wide range of activities that allow
      proposing them as new leads for development of a natural herbicide model with a
      seco-guaianolide skeleton. 

PMID- 23148701
TI  - Tautomerization in the UDP-galactopyranose mutase mechanism: a DFT-cluster and
      QM/MM investigation.
AB  - UDP-galactopyranose mutase (UGM) is a key flavoenzyme involved in cell wall
      biosynthesis of a variety of pathogenic bacteria and hence, integral to their
      survival. It catalyzes the interconversion of UDP-galactopyranose (UDP-Galp) and
      UDP-galactofuranose (UDP-Galf); interconversion of the galactose moieties six-
      and five-membered ring forms. We have synergistically applied both density
      functional theory (DFT)-cluster and ONIOM quantum mechanics/molecular mechanics
      (QM/MM) hybrid calculations to elucidate the mechanism of this important enzyme
      and to provide insight into its uncommon mechanism. It is shown that the flavin
      must initially be in its fully reduced form. Furthermore, it requires an N5(FAD)
      H proton, which, through a series of tautomerizations, is transferred onto the
      ring oxygen of the substrate's Galp moiety to facilitate ring-opening with
      concomitant Schiff base formation. Conversely, Galf formation is achieved via a
      series of tautomerizations involving proton transfer from the galactose's 
      O4(Gal)H group ultimately onto the flavin's N5(FAD) center. With the DFT-cluster
      model, the overall rate-limiting step with a barrier of 120.0 kJ mol(-1) is the
      interconversion of two Galf-flavin tautomers: one containing a C4(FAD)-OH group
      and the other a tetrahedral protonated-N5(FAD) center. In contrast, in the QM/MM
      model a considerably more extensive chemical model was used that included all of
      the residues surrounding the active site, and modeled both their steric and
      electrostatic effects. In this approach, the overall rate-limiting step with a
      barrier of 99.2 kJ mol(-1) occurs during conformational rearrangement of the
      Schiff base linear galactose-flavin complex. This appears due to the lack of
      suitable functional groups to facilitate the rearrangement.

PMID- 23148702
TI  - Highly accurate nitrogen dioxide (NO2) in nitrogen standards based on permeation.
AB  - The development and operation of a highly accurate primary gas facility for the
      dynamic production of mixtures of nitrogen dioxide (NO(2)) in nitrogen (N(2))
      based on continuous weighing of a permeation tube and accurate impurity
      quantification and correction of the gas mixtures using Fourier transform
      infrared spectroscopy (FT-IR) is described. NO(2) gas mixtures in the range of 5
      MUmol mol(-1) to 15 MUmol mol(-1) with a standard relative uncertainty of 0.4%
      can be produced with this facility. To achieve an uncertainty at this level,
      significant efforts were made to reduce, identify and quantify potential
      impurities present in the gas mixtures, such as nitric acid (HNO(3)). A complete
      uncertainty budget, based on the analysis of the performance of the facility,
      including the use of a FT-IR spectrometer and a nondispersive UV analyzer as
      analytical techniques, is presented in this work. The mixtures produced by this
      facility were validated and then selected to provide reference values for an
      international comparison of the Consultative Committee for Amount of Substance
      (CCQM), number CCQM-K74, (1)  which was designed to evaluate the consistency of
      primary NO(2) gas standards from 17 National Metrology Institutes.

PMID- 23148703
TI  - A multidimensional framework for the meanings of the sexual double standard and
      its application for the sexual health of young black women in the U.S.
AB  - There has been debate in the literature as to whether a sexual double standard
      (SDS) currently exists in the United States. Studies vary greatly in how the SDS
      is operationalized, making it difficult to interpret findings across studies and
      translate academic literature into applied fields such as public health. To
      advance academic and applied research, we propose a multidimensional framework
      for the SDS that can accommodate complex and nuanced meanings, is flexible enough
      to allow for the dynamic nature of social ideologies, and is grounded in an
      understanding of social systems of inequality. In this article, we describe three
      dimensions that define the broad elements of the SDS: (a) polarized
      (hetero)sexualities, (b) active male and passive female roles, and (c) the power
      struggle narrative. To illustrate the use of the framework, we contextualize each
      dimension in terms of the intersection of race and gender for young Black women
      in the United States. And finally, to apply the framework, we explore the effects
      the SDS can have on sexual health and suggest some directions for public health
      interventions. These analyses lay the groundwork for more complex and
      comprehensive investigations of the SDS and its effects on sexual health. 

PMID- 23148705
TI  - Direct evidence of nonadherence to antiepileptic medication in refractory focal
      epilepsy.
AB  - The adherence to medication in drug-resistant focal epilepsy (RFE) remains
      largely unknown. The present work aimed to assess the frequency of recent
      adherence to antiepileptic drugs (AEDs) in patients with RFE. This prospective
      observational study screened all patients with RFE, admitted to the Nancy
      University Hospital between April 2006 and September 2008, for a 5-day
      hospitalization without AED tapering. The adherence to AEDs was assessed by
      measuring serum drug levels on day 1 (reflecting the recent "at home" adherence)
      and day 5 (reflecting the individual reference concentration when drug ingestion
      was supervised). A patient was considered nonadherent if at least one of their
      serum drug levels was different between days 1 and 5. The day-1 value was
      considered different from day 5 when it was at least 30% lower (underdosed) or
      30% higher (overdosed). Nonadherent patients were classified as under-consumers
      in the case of one or more underdosed day-1 values, over-consumers in the case of
      one or more overdosed day-1 values, or undefined if they exhibited both
      underdosed and overdosed day-1 values. Forty-four of the 48 screened patients
      were included. Eighteen (40.9%) of 44 patients were nonadherent. Among them, 12
      (66.7%) were over-consumers, 4 (22.2%) were under-consumers, and 2 (11.1%) were
      undefined nonadherents. The study indicates that recent adherence to
      antiepileptic medication in this group of patients with RFE is poor.
      Overconsumption is the most frequent form of nonadherence in this population and
      should be specifically assessed to prevent its possible consequences in terms of
      AEDs dose-dependent adverse events.

PMID- 23148704
TI  - Murine Borrelia arthritis is highly dependent on ASC and caspase-1, but
      independent of NLRP3.
AB  - INTRODUCTION: The protein platform called the NOD-like-receptor -family member
      (NLRP)-3 inflammasome needs to be activated to process intracellular caspase-1.
      Active caspase-1 is able to cleave pro-Interleukin (IL)-1beta, resulting in
      bioactive IL-1beta. IL-1beta is a potent proinflammatory cytokine, and thought to
      play a key role in the pathogenesis of Lyme arthritis, a common manifestation of
      Borrelia burgdorferi infection. The precise pathways through which B. burgdorferi
      recognition leads to inflammasome activation and processing of IL-1beta in Lyme
      arthritis has not been elucidated. In the present study, we investigated the
      contribution of several pattern recognition receptors and inflammasome components
      in a novel murine model of Lyme arthritis. METHODS: Lyme arthritis was elicited
      by live B. burgdorferi, injected intra-articularly in knee joints of mice. To
      identify the relevant pathway components, the model was applied to wild-type,
      NLRP3-/-, ASC-/-, caspase-1-/-, NOD1-/-, NOD2-/-, and RICK-/- mice. As a control,
      TLR2-/-, Myd88-/- and IL-1R-/- mice were used. Peritoneal macrophages and bone
      marrow-derived macrophages were used for in vitro cytokine production and
      inflammasome activation studies. Joint inflammation was analyzed in synovial
      specimens and whole knee joints. Mann-Whitney U tests were used to detect
      statistical differences. RESULTS: We demonstrate that ASC/caspase-1-driven IL
      1beta is crucial for induction of B. burgdorferi-induced murine Lyme arthritis.
      In addition, we show that B. burgdorferi-induced murine Lyme arthritis is less
      dependent on NOD1/NOD2/RICK pathways while the TLR2-MyD88 pathway is crucial.
      CONCLUSIONS: Murine Lyme arthritis is strongly dependent on IL-1 production, and
      B. burgdorferi induces inflammasome-mediated caspase-1 activation. Next to that,
      murine Lyme arthritis is ASC- and caspase-1-dependent, but NLRP3, NOD1, NOD2, and
      RICK independent. Also, caspase-1 activation by B. burgdorferi is dependent on
      TLR2 and MyD88. Based on present results indicating that IL-1 is one of the major
      mediators in Lyme arthritis, there is a rationale to propose that neutralizing IL
      1 activity may also have beneficial effects in chronic Lyme arthritis.

PMID- 23148707
TI  - Lung cancer presenting as a metastasis to the carpal bones: a case report.
AB  - INTRODUCTION: A first metastasis to the hand is extremely rare. Usually, an
      acrometastasis is a sign of very advanced disease, with the presence of previous
      multiple metastases elsewhere. The present paper is one of the very few case
      reports of first metastatic location to carpal bones. To date, only Lederer et
      al., in 1990, and Song and Yao in 2012, have described a metastasis to the
      trapezium from lung cancer. CASE PRESENTATION: A 74-year-old Caucasian man was
      submitted to several physical examinations for thumb pain. The first diagnosis
      was tendonitis and the second diagnosis was thumb carpometacarpal osteoarthritis.
      Only when the patient was admitted to an internal medicine department for
      deterioration of his general condition and an enormous mass on his left hand was
      an open biopsy performed. It revealed a metastasis from large-cell lung
      carcinoma. A total-body scintigraphy and total-body computed tomography scan were
      negative for other secondary locations. The patient underwent an amputation at
      the distal third of the forearm. CONCLUSION: Less than 20 case reports are
      available in the literature dealing with metastases to carpal bones. Very few
      cases are described as carpal metastases in the absence of other previous
      metastases, and only two articles, before the present one, have reported a
      metastasis to the trapezium. This case report teaches us two things: first,
      patient adherence to follow-up is extremely important; and, second, a thorough
      examination of diagnostic findings needs to be carried out at all times.

PMID- 23148706
TI  - Autoantibody against transient receptor potential M1 cation channels of retinal
      ON bipolar cells in paraneoplastic vitelliform retinopathy.
AB  - BACKGROUND: Paraneoplastic retinopathy is caused by the cross-reaction of
      neoplasm-directed autoantibodies against retinal antigens and results in retinal
      damage. Paraneoplastic vitelliform retinopathy, a presumed paraneoplastic
      retinopathy with features of atypical melanoma-associated retinopathy, has
      recently been reported in patients with metastatic melanoma. Ocular
      ultrastructure and its autoantibody localization of paraneoplastic vitelliform
      retinopathy are still indefinable. This is the first report of anti-transient
      receptor potential M1 antibody directly against human retinal bipolar dendritic
      tips in a melanoma patient with paraneoplastic vitelliform retinopathy. CASE
      PRESENTATION: We present a pair of postmortem eyes of an 80-year-old male with
      metastatic cutaneous melanoma, who developed paraneoplastic vitelliform
      retinopathy. The autopsied eyes were examined with light microscopy,
      immunohistochemistry, and transmission electron microscopy. Microscopically, the
      inner nuclear layer and outer plexiform layer were the most affected retinal
      structures, with local thinning. The lesions extended to the outer nuclear layer,
      resulting in focal retinal degeneration, edema, and atrophy. No active
      inflammation or melanoma cells were observed. Immunohistochemistry showed tightly
      compact bipolar cell nuclei (protein kinase C alpha/calbindin positive) with
      blur/loss of ON bipolar cell dendritic tips (transient receptor potential M1
      positive) in diffusely condensed outer plexiform layer. The metastatic melanoma
      cells in his lung also showed immunoreactivity against transient receptor
      potential M1 antibody. Transmission electron microscopy illustrated degenerated
      inner nuclear layer with disintegration of cells and loss of cytoplasmic
      organelles. These cells contained many lysosomal and autophagous bodies and
      damaged mitochondria. Their nuclei appeared pyknotic and fragmentary. The
      synapses in the outer plexiform layer were extensively degenerated and replaced
      with empty vacuoles and disintegrated organelles. CONCLUSION: This case provides
      a convincing histological evidence of melanoma-associated autoantibodies directly
      against transient receptor potential M1 channels that target the ON bipolar cell
      structures in the inner nuclear and outer plexiform layers in paraneoplastic
      vitelliform retinopathy.

PMID- 23148708
TI  - Sexual cognition guides viewing strategies to human figures.
AB  - Gaze patterns to figure images have been proposed to reflect the observer's
      sexual interest, particularly for men. This eye-tracking study investigated how
      individual differences in sexual motivation tendencies are manifested in
      naturalistic gaze patterns. Heterosexual men and women (M = 21.0 years, SD = 2.1)
      free-viewed plain-clothed male and female figures, aged 10, 20, and 40 years old,
      while their eye movements were recorded. Questionnaires were used to measure
      sexual cognitions, including sensation seeking and sexual compulsivity, sexual
      inhibition and excitation, and approach and avoidance responses to sexual
      stimuli. Our analysis showed a clear role of sexual cognitions in influencing
      gaze strategies for men. Specifically, men who scored higher on sexual
      compulsivity dedicated more gaze to the waist-hip region when viewing figures of
      their preferred sexual partners than men who scored lower on sexual compulsivity.
      Women's sexual cognitions showed no clear effect on the gaze pattern in viewing
      figures of their preferred age and gender of sexual partners, suggesting women's
      gaze is unlikely to be a straightforward reflection of their sexual preferences.
      The findings further suggest that men's gaze allocation is driven by sexual
      preferences and supports the utility of eye tracking in the assessment of male
      sexual interest. 

PMID- 23148709
TI  - Good-bye CRRT, here comes SLED? ... not so fast!
AB  - In the continuing dispute about the superiority of either intermittent or
      continuous renal replacement therapy for the critically ill, hybrid methods such
      as sustained low-efficiency dialysis (SLED) combining the advantages of both
      modalities--that is, excellent hemodynamic stability and low costs--receive
      growing attention. The study by Schwenger and colleagues is the first randomized
      trial indicating that there may be no significant difference in survival at 90
      days between patients treated with SLED as compared with those treated with
      continuous veno-venous hemofiltration.

PMID- 23148710
TI  - Serum infliximab concentrations in pediatric inflammatory bowel disease.
AB  - OBJECTIVE: To study serum infliximab (s-IFX) levels in pediatric patients with
      inflammatory bowel disease (IBD). SUBJECTS AND METHODS: s-IFX trough levels were
      measured in a total of 133 blood samples of 37 pediatric IBD patients (Crohn's
      disease, 23): 48 during the induction phase (weeks 2 and 6) and 85 during
      maintenance treatment. Antibodies to infliximab (ATI) were determined in 93
      samples (30 patients). s-IFX values were related to fecal calprotectin (FC) and
      serum markers of inflammation. RESULTS: During induction (5 mg/kg) and
      maintenance therapy, the median s-IFX levels were 17.6 MUg/ml (range 0-48 MUg/ml)
      and 3.55 MUg/ml (range 0-40 MUg/ml), respectively. The IFX levels were similar in
      ulcerative colitis and Crohn's disease (e.g. during maintenance median 3.2 vs.
      2.8 MUg/ml, p = 0.718), thus the data are pooled. During induction, the s-IFX
      level was associated with the total dose of IFX, that is, young children with
      lower body weight had lower levels (p < 0.001 at week 2 and p < 0.05 at week 6).
      Shorter administration interval resulted in higher trough levels (p < 0.005). All
      samples with undetectable s-IFX (6.8%) levels presented ATI. High inflammation
      (FC >1000 ug/g) during induction was associated with lower s-IFX levels (median
      4.0 MUg/ml, range 0.47-25 compared to median 20 MUg/ml, range 0-48 when FC <1000
      ug/g, p < 0.005). There was no significant association between the ESR or values
      of C-reactive protein and s-IFX levels during induction. CONCLUSIONS: In
      pediatric IBD, lower body weight and higher level of intestinal inflammation are
      associated to s-IFX levels during induction but relation to therapeutic response
      is unclear.

PMID- 23148711
TI  - Deduction of bond length changes of symmetric molecules from experimental
      vibrational progressions, including a topological mass factor.
AB  - The change DeltaR(x) of bond length R(x) for atom X in a molecule upon electronic
      transition can be derived from the intensities I(i) of the vibrational stretching
      progression v = 0 -> i of the electronic absorption or emission spectrum. In many
      cases, a simple model is sufficient for a reasonable estimate of DeltaR(x). For
      symmetric molecules, however, conceptual problems in the literature of many
      decades are evident. The breathing modes of various types of symmetric molecules
      X(n) and AX(n) (A at the center) are here discussed. In the simplest case of a
      harmonic vibration of the same mode in the initial and final electronic states,
      we obtain DeltaR(x) ~ [2S/(omegam(x))](1/2)/w(1/2) (all quantities in atomic
      units). omega and S are respectively the observed vibrational quanta and the
      Huang-Rhys factor (corresponding, e.g., to the vibrational intensity ratio
      I(1)/I(0) ~ S), m(x) is the mass of vibrating atom X, and w is a topological
      factor for molecule X(n) or AX(n). The factor 1/w(1/2) in the expression for
      DeltaR(x) must not be neglected. The spectra and bond length changes of several
      symmetric molecules AX(n) and X(n) are discussed. The experimental bond length
      changes correctly derived with factor 1/w(1/2) are verified by reliable quantum
      chemical calculations.

PMID- 23148712
TI  - Comparison of oncological outcomes for open and laparoscopic radical
      nephroureterectomy: results from the Canadian Upper Tract Collaboration.
AB  - WHAT'S KNOWN ON THE SUBJECT? AND WHAT DOES THE STUDY ADD?Open radical
      nephroureterectomy (ORNU) with excision of the ipsilateral bladder cuff is a
      standard treatment for upper tract urothelial carcinoma (UTUC). However, over the
      past decade laparoscopic RNU (LRNU) has emerged as a minimally invasive surgical
      alternative. Data comparing the oncological efficacy of ORNU and LRNU have
      reported mixed results and the equivalence of these surgical techniques have not
      yet been established. We found that surgical approach was not independently
      associated with overall or disease-specific survival; however, there was a trend
      toward an independent association between LRNU and poorer recurrence-free
      survival (RFS). To our knowledge, this is the first large, multi-institutional
      analysis to show a trend toward inferior RFS in patients with UTUC treated with
      LRNU. OBJECTIVE: To examine the association between surgical approach for radical
      nephroureterectomy (RNU) and clinical outcomes in a large, multi-institutional
      cohort, as there are limited data comparing the oncological efficacy of open RNU
      (ORNU) and laparoscopic RNU (LRNU) for upper urinary tract urothelial carcinoma
      (UTUC). PATIENTS AND METHODS: Institutional RNU databases containing detailed
      information on patients with UTUC treated between 1994 and 2009 were obtained
      from 10 academic centres in Canada. Data were collected on 1029 patients and
      combined into a relational database formatted with patient characteristics,
      pathological characteristics, and survival status. Surgical approach was
      classified as ORNU (n = 403) or LRNU (n = 446). The clinical outcomes were
      overall survival (OS), disease-specific survival (DSS), and recurrence-free
      survival (RFS). The Kaplan-Meier method and Cox proportional regression analysis
      were used to analyse survival data. RESULTS: Data were evaluable for 849 of 1029
      (82.5%) patients. The median (interquartile range) follow-up duration was 2.2
      (0.6-5.0) years. The predicted 5-year OS (67% vs 68%, log-rank P = 0.19) and DSS
      (73% vs 76%, log-rank P = 0.32) rates did not differ between the ORNU and LRNU
      groups; however, there was a trend toward an improved predicted 5-year RFS rate
      in the ORNU group (43% vs 33%, log-rank P = 0.06). Multivariable Cox proportional
      regression analysis showed that surgical approach was not significantly
      associated with OS (hazard ratio [HR] 0.89, 95% confidence interval [CI] 0.63
      1.27, P = 0.52) or DSS (HR 0.90, 95% CI 0.60-1.37, P = 0.64); however, there was
      a trend toward an independent association between surgical approach and RFS (HR
      1.24, 95% CI 0.98-1.57, P = 0.08). CONCLUSION: Surgical approach was not
      independently associated with OS or DSS but there was a trend toward an
      independent association between LRNU and poorer RFS. Further prospective
      evaluation is needed.

PMID- 23148714
TI  - The tripartite efficacy framework in client-therapist rehabilitation
      interactions: implications for relationship quality and client engagement.
AB  - PURPOSE: Within supervised rehabilitation programs, Lent and Lopez (2002)
      proposed that clients and therapists develop a "tripartite" network of efficacy
      beliefs, comprising their confidence in their own ability, their confidence in
      the other person's ability, and their estimation of the other person's confidence
      in them. To date, researchers have yet to explore the potential relational
      outcomes associated with this model in rehabilitation contexts. METHOD: In Study
      1, we recruited 170 exercise clients (Mage = 63.73, SD = 6.46) who were enrolled
      in a one-to-one aerobic exercise program with a therapist as a result of a lower
      limb musculoskeletal disorder. Clients reported their tripartite efficacy beliefs
      and perceptions about the quality of their relationship with their therapist, and
      respective therapists rated each client's engagement in his or her exercise
      program. In Study 2, we recruited 68 separate exercise clients (Mage = 65.93, SD
      = 5.80) along with their therapists (n = 68, Mage = 31.89, SD = 4.79) from the
      same program, to examine whether individuals' efficacy perceptions were related
      to their own and/or the other person's relationship quality perceptions. RESULTS:
      In Study 1, each of the tripartite efficacy constructs displayed positive direct
      effects with respect to clients' relationship quality appraisals, as well as
      indirect effects in relation to program engagement. Actor-partner interdependence
      modeling in Study 2 demonstrated that clients and therapists reported more
      adaptive relationship perceptions when they themselves held strong tripartite
      efficacy beliefs (i.e., actor effects), and that clients viewed their
      relationship in a more positive light when their therapist was highly confident
      in the client's ability (i.e., partner effect). CONCLUSION: These findings
      underscore the potential utility of the tripartite efficacy framework in relation
      to motivational and relational processes within supervised exercise programs.

PMID- 23148713
TI  - Attachment style is associated with perceived spouse responses and pain-related
      outcomes.
AB  - PURPOSE/OBJECTIVE: Attachment theory can provide a heuristic model for examining
      factors that may influence the relationship of social context to adjustment in
      chronic pain. This study examined the associations of attachment style with self
      reported pain behavior, pain intensity, disability, depression, and perceived
      spouse responses to pain behavior. We also examined whether attachment style
      moderates associations between perceived spouse responses and self-reported pain
      behavior and depressive symptoms, as well as perceived spouse responses as a
      mediator of these associations. METHOD: Individuals with chronic pain (N = 182)
      completed measures of self-reported attachment style, perceived spouse responses,
      and pain-related criterion variables. RESULTS: Secure attachment was inversely
      associated with self-reported pain behaviors, pain intensity, disability,
      depressive symptoms, and perceived negative spouse responses; preoccupied and
      fearful attachment scores were positively associated with these variables. In
      multivariable regression models, both attachment style and perceived spouse
      responses were uniquely associated with self-reported pain behavior and
      depressive symptoms. Attachment style did not moderate associations between
      perceived spouse responses to self-reported pain behavior and pain criterion
      variables, but negative spouse responses partially mediated some relationships
      between attachment styles and pain outcomes. CONCLUSIONS/IMPLICATIONS: Findings
      suggest that attachment style is associated with pain-related outcomes and
      perceptions of spouse responses. The hypothesized moderation effects for
      attachment were not found; however, mediation analyses showed that perceived
      spouse responses may partially explain associations between attachment and
      adjustment to pain. Future research is needed to clarify how attachment style and
      the social environment affect the pain experience.

PMID- 23148715
TI  - Helping people with HIV/AIDS return to work: a randomized clinical trial.
AB  - OBJECTIVE: New treatments introduced in the mid-1990s led many people with
      HIV/AIDS who previously had been disabled by their disease to contemplate
      workforce reentry; many remain unemployed, and little is known concerning
      interventions that might help them return to work. We report the results of a
      randomized clinical trial of an intervention designed to help people with
      HIV/AIDS reenter the workforce. DESIGN: We tested a mixed (group-individual)
      modality intervention that incorporated elements of Motivational Interviewing
      (Miller & Rollnick, 2002), skills building from Dialectical Behavior Therapy
      (Linehan, 1993), and job-related skills (Price & Vinokur, 1995). A total of 174
      individuals participated in either the intervention or in standard of care and
      were followed for 24 months. RESULTS: Compared with individuals referred for
      standard of care, participants in the intervention engaged in more workforce
      reentry activities over time and, once employed, were more likely to remain
      employed. Dose-response analyses revealed that among intervention participants,
      participants who attended more than 1 individual session engaged in more
      workforce-reentry activities than individuals who attended 1 or fewer individual
      sessions, whereas frequency of group session participation did not effect a
      difference between participants who attended more than 6 group sessions and
      participants who attended 6 or fewer group sessions. CONCLUSION: Theoretically
      based workforce-reentry assistance programs can assist disabled people with
      HIV/AIDS in their return-to-work efforts.

PMID- 23148716
TI  - Pre-capture multiplexing improves efficiency  and cost-effectiveness of targeted
      genomic enrichment.
AB  - BACKGROUND: Targeted genomic enrichment (TGE) is a widely used method for
      isolating and enriching specific genomic regions prior to massively parallel
      sequencing. To make effective use of sequencer output, barcoding and sample
      pooling (multiplexing) after TGE and prior to sequencing (post-capture
      multiplexing) has become routine. While previous reports have indicated that
      multiplexing prior to capture (pre-capture multiplexing) is feasible, no thorough
      examination of the effect of this method has been completed on a large number of
      samples. Here we compare standard post-capture TGE to two levels of pre-capture
      multiplexing: 12 or 16 samples per pool. We evaluated these methods using
      standard TGE metrics and determined the ability to identify several classes of
      genetic mutations in three sets of 96 samples, including 48 controls. Our overall
      goal was to maximize cost reduction and minimize experimental time while
      maintaining a high percentage of reads on target and a high depth of coverage at
      thresholds required for variant detection. RESULTS: We adapted the standard post
      capture TGE method for pre-capture TGE with several protocol modifications,
      including redesign of blocking oligonucleotides and optimization of enzymatic and
      amplification steps. Pre-capture multiplexing reduced costs for TGE by at least
      38% and significantly reduced hands-on time during the TGE protocol. We found
      that pre-capture multiplexing reduced capture efficiency by 23 or 31% for pre
      capture pools of 12 and 16, respectively. However efficiency losses at this step
      can be compensated by reducing the number of simultaneously sequenced samples.
      Pre-capture multiplexing and post-capture TGE performed similarly with respect to
      variant detection of positive control mutations. In addition, we detected no
      instances of sample switching due to aberrant barcode identification.
      CONCLUSIONS: Pre-capture multiplexing improves efficiency of TGE experiments with
      respect to hands-on time and reagent use compared to standard post-capture TGE. A
      decrease in capture efficiency is observed when using pre-capture multiplexing;
      however, it does not negatively impact variant detection and can be accommodated
      by the experimental design.

PMID- 23148717
TI  - Right thyroid hemiagenesis with adenoma and hyperplasia of parathyroid glands 
      case report.
AB  - BACKGROUND: Thyroid hemiagenesis is a rare anomaly, more commonly seen on the
      left side (ratio 4:1) and in females (ratio 3:1). The first to describe this
      anomaly was Handfield Jones in 1852. CASE PRESENTATION: We present a 66 year old
      female patient with right thyroid hemiagenesis, parathyroid adenoma on the side
      of hemiagenesis and parathyroid hyperplasia on the contralateral side. The
      patient had neck pain and was diagnosed as Hashimto thyroiditis with
      hyperparathyroidism. Parathyroid hormone, thyroglobulin antibodies (Tg-Ab) and
      thyroid peroxidase antibodies (TPO-Ab) were elevated. Neck ultrasound and
      technetium 99mTc-methoxyisobutyl isonitrile (MIBI) scintigraphy confirmed the
      right thyroid hemiagenesis, but not adenoma of parathyroid glands.
      Intraoperatively, right thyroid hemiagenesis was confirmed and left
      loboistmectomy was performed with removal of left inferior hyperplastic
      parathyroid gland. Postoperative PTH (parathyroid hormone) levels were within
      normal range. Five months after the operation PTH level was elevated again with
      calcium values at the upper limit. MIBI scintigraphy was performed again which
      showed increased accumulation of MIBI in the projection of the right parathyroid
      gland. Surgical reexploration of the neck and excision of the right upper
      parathyroid adenoma was performed which was located behind cricoid laryngeal
      cartilage. After surgery a normalization of calcium and PTH occured. CONCLUSION:
      From available literature we have not found the case that described parathyroid
      adenoma on the side of thyroid hemiagenesis,with parathyroid hyperplasia on the
      contralateral side.

PMID- 23148718
TI  - Measurement of overall insecticidal effects in experimental hut trials.
AB  - BACKGROUND: The 'overall insecticidal effect' is a key measure used to evaluate
      public health pesticides for indoor use in experimental hut trials. It depends on
      the proportion of mosquitoes that are killed out of those that enter the treated
      hut, intrinsic mortality in the control hut, and the ratio of mosquitoes entering
      the treatment hut to those entering the control hut. This paper critically
      examines the way the effect is defined, and discusses how it can be used to infer
      effectiveness of intervention programmes. FINDINGS: The overall insecticidal
      effect, as defined by the World Health Organization in 2006, can be negative when
      deterrence from entering the treated hut is high, even if all mosquitoes that
      enter are killed, wrongly suggesting that the insecticide enhances mosquito
      survival. Also in the absence of deterrence, even if the insecticide kills all
      mosquitoes in the treatment hut, the insecticidal effect is less than 100%,
      unless intrinsic mortality is nil. A proposed alternative definition for the
      measurement of the overall insecticidal effect has the desirable range of 0 to 1
      (100%), provided mortality among non-repelled mosquitoes in the treated hut is
      less than the corresponding mortality in the control hut. This definition can be
      built upon to formulate the coverage-dependent insecticidal effectiveness of an
      intervention programme. Coverage-dependent population protection against feeding
      can be formulated similarly. CONCLUSIONS: This paper shows that the 2006
      recommended quantity for measuring the overall insecticidal effect is
      problematic, and proposes an alternative quantity with more desirable properties.

PMID- 23148719
TI  - Iron oxide filled magnetic carbon nanotube-enzyme conjugates for recycling of
      amyloglucosidase: toward useful applications in biofuel production process.
AB  - Biofuels are fast advancing as a new research area to provide alternative sources
      of sustainable and clean energy. Recent advances in nanotechnology have sought to
      improve the efficiency of biofuel production, enhancing energy security. In this
      study, we have incorporated iron oxide nanoparticles into single-walled carbon
      nanotubes (SWCNTs) to produce magnetic single-walled carbon nanotubes (mSWCNTs).
      Our objective is to bridge both nanotechnology and biofuel production by
      immobilizing the enzyme, Amyloglucosidase (AMG), onto mSWCNTs using physical
      adsorption and covalent immobilization, with the aim of recycling the immobilized
      enzyme, toward useful applications in biofuel production processes. We have
      demonstrated that the enzyme retains a certain percentage of its catalytic
      efficiency (up to 40%) in starch prototype biomass hydrolysis when used
      repeatedly (up to ten cycles) after immobilization on mSWCNTs, since the
      nanotubes can be easily separated from the reaction mixture using a simple
      magnet. The enzyme loading, activity, and structural changes after immobilization
      onto mSWCNTs were also studied. In addition, we have demonstrated that the
      immobilized enzyme retains its activity when stored at 4  degrees C for at least
      one month. These results, combined with the unique intrinsic properties of the
      nanotubes, pave the way for greater efficiency in carbon nanotube-enzyme
      bioreactors and reduced capital costs in industrial enzyme systems.

PMID- 23148722
TI  - Epitaxial graphene on 4H-SiC(0001) grown under nitrogen flux: evidence of low
      nitrogen doping and high charge transfer.
AB  - Nitrogen doping of graphene is of great interest for both fundamental research to
      explore the effect of dopants on a 2D electrical conductor and applications such
      as lithium storage, composites, and nanoelectronic devices. Here, we report on
      the modifications of the electronic properties of epitaxial graphene thanks to
      the introduction, during the growth, of nitrogen-atom substitution in the carbon
      honeycomb lattice. High-resolution transmission microscopy and low-energy
      electron microscopy investigations indicate that the nitrogen-doped graphene is
      uniform at large scale. The substitution of nitrogen atoms in the graphene planes
      was confirmed by high-resolution X-ray photoelectron spectroscopy, which reveals
      several atomic configurations for the nitrogen atoms: graphitic-like, pyridine
      like, and pyrrolic-like. Angle-resolved photoemission measurements show that the
      N-doped graphene exhibits large n-type carrier concentrations of 2.6 * 10(13) cm(
      2), about 4 times more than what is found for pristine graphene, grown under
      similar pressure conditions. Our experiments demonstrate that a small amount of
      dopants (<1%) can significantly tune the electronic properties of graphene by
      shifting the Dirac cone about 0.3 eV toward higher binding energies with respect
      to the pi band of pristine graphene, which is a key feature for envisioning
      applications in nanoelectronics.

PMID- 23148724
TI  - Meroterpenoid and diphenyl ether derivatives from Penicillium sp. MA-37, a fungus
      isolated from marine mangrove rhizospheric soil.
AB  - Penicillium sp. MA-37, which was obtained from the rhizospheric soil of the
      mangrove plant Bruguiera gymnorrhiza, exhibited different chemical profiles in
      static and shaken fermentation modes. Three new meroterpenoid derivatives, 4,25
      dehydrominiolutelide B (1), 4,25-dehydro-22-deoxyminiolutelide B (2), and
      isominiolutelide A (3), together with three known ones were characterized from
      its static fermentation, while three new diphenyl ether derivatives, namely,
      Delta(1('),3('))-1'-dehydroxypenicillide (4), 7-O-acetylsecopenicillide C (5),
      and hydroxytenellic acid B (6), along with five related metabolites were isolated
      from the shaken culture. The structures of these compounds were elucidated on the
      basis of spectroscopic analysis, and the structure of compound 2 was confirmed by
      X-ray crystallographic analysis. The absolute configurations of 1-3 and 6 were
      determined by ECD and modified Mosher's method, respectively. All isolated
      compounds were evaluated for brine shrimp lethality and antibacterial activity. 

PMID- 23148725
TI  - Ilarviruses of Prunus spp.: a continued concern for fruit trees.
AB  - Prunus spp. are affected by a large number of viruses, causing significant
      economic losses through either direct or indirect damage, which results in
      reduced yield and fruit quality. Among these viruses, members of the genus
      Ilarvirus (isometric labile ringspot viruses) occupy a significant position due
      to their distribution worldwide. Although symptoms caused by these types of
      viruses were reported early in the last century, their molecular characterization
      was not achieved until the 1990s, much later than for other agronomically
      relevant viruses. This was mainly due to the characteristic liability of virus
      particles in tissue extracts. In addition, ilarviruses, together with Alfalfa
      mosaic virus, are unique among plant viruses in that they require a few molecules
      of the coat protein in the inoculum in order to be infectious, a phenomenon known
      as genome activation. Another factor that has made the study of this group of
      viruses difficult is that infectious clones have been obtained only for the type
      member of the genus, Tobacco streak virus. Four ilarviruses, Prunus necrotic
      ringspot virus, Prune dwarf virus, Apple mosaic virus, and American plum line
      pattern virus, are pathogens of the main cultivated fruit trees. As stated in the
      9th Report of the International Committee on Taxonomy of Viruses, virions of this
      genus are "unpromising subjects for the raising of good antisera." With the
      advent of molecular approaches for their detection and characterization, it has
      been possible to get a more precise view of their prevalence and genome
      organization. This review updates our knowledge on the incidence, genome
      organization and expression, genetic diversity, modes of transmission, and
      diagnosis, as well as control of this peculiar group of viruses affecting fruit
      trees.

PMID- 23148723
TI  - Follow-ups of metabolic, inflammatory and oxidative stress markers, and brachial
      ankle pulse wave velocity in middle-aged subjects without metabolic syndrome.
AB  - This study investigates the association among metabolic risk factors,
      inflammatory and oxidative stress markers, and brachial-ankle pulse wave velocity
      (ba-PWV). We conducted a 3-year longitudinal, observational study of 288 middle
      aged adults not meeting the criteria for metabolic syndrome (MetS) at the initial
      screening. We measured metabolic risk factors, inflammatory and oxidative stress
      markers, and ba-PWV. Within the 3-year study period, 15.6% (45 out of 288) of
      participants developed MetS. At the 3-year follow-up, patients were categorized
      as those with MetS (n = 45) and those without MetS (n = 243). Patients with MetS
      had significantly unfavorable initial measurements of baseline body mass index
      (BMI), waist circumference (WC), blood pressure (BP), triglyceride (TG), high
      density lipoprotein (HDL)-cholesterol, glucose, insulin, homeostasis model
      assessment of insulin resistance (HOMA-IR) index, and ba-PWV. After 3 years,
      participants without MetS showed significant increases in WC, diastolic BP (DBP),
      total- and low-density lipoprotein (LDL)-cholesterol, malondialdehyde (MDA),
      oxidized-LDL (ox-LDL), and ba-PWV and a significant decrease in HDL-cholesterol
      and free fatty acids (FFA). Subjects who developed MetS showed significant
      increases in BMI, WC, BP, TG, glucose, interleukin-6 (IL-6), tumor necrosis
      factor-alpha (TNF-alpha), MDA, ox-LDL, and ba-PWV and a significant decrease in
      HDL-cholesterol. Changes in BMI, WC, BP, TG, HDL-cholesterol, glucose, HOMA-IR
      index, FFA, C-reactive protein (P = .022), IL-6 (P = .004), leukocyte count (P <
      .001), MDA (P = .002), ox-LDL (P = .015), and ba-PWV (P = .001) differed
      significantly between the two groups after adjustment for baseline values.
      Changes in ba-PWV were positively correlated with the changes in systolic and
      DBP, total-cholesterol, glucose, leukocyte count, and MDA. The age-related
      increase in arterial stiffness is greater in the presence of MetS with higher
      levels of inflammatory and oxidative stress markers. 

PMID- 23148727
TI  - Stress-related asthma and family therapy: Case study.
AB  - This paper applies the Biobehavioral Family Model (BBFM) of stress- related
      illness to the study and treatment of an adolescent with intractable asthma. The
      model is described, along with supportive research findings. Then a case study is
      presented, demonstrating how the model is clinically applied. We tell the story
      of an asthmatic adolescent presenting for therapy due to her intense asthmatic
      crises, and the case is presented to exemplify how the BBFM can help understand
      the family-psychobiological contribution to exacerbation of disease activity, and
      therefore guide treatment towards the amelioration of severe physical symptoms.
      Facets of the patient's intra-familial interactions are consistent with the BBFM,
      which support clinical validation of the model. In the case described, it is
      likely that additional asthma medications would not have had the desired
      ameliorative effect, because they did not target the family relational processes
      contributing to the symptoms. The recognition of the influences of family
      relational processes on the disease was crucial for effective intervention. The
      therapy incorporates and weaves together BBFM understanding of family patterns of
      interaction and physiological/medical concerns integrated with Bowenian
      intervention strategies. This case study validates the importance and usefulness
      of BBFM for intervention with stress-sensitive illnesses such as asthma.

PMID- 23148728
TI  - Ferryl-oxo species produced from Fenton's reagent via a two-step pathway: minimum
      free-energy path analysis.
AB  - A mixture of ferrous ions and hydrogen peroxide, known as Fenton's reagent, is an
      effective oxidant and has been widely used in various industrial applications;
      however, there is still controversy about what the oxidizing agents are and how
      they are produced. In this study, we have determined minimum free-energy paths
      (MFEPs) from Fenton's reagent to possible oxidizing agents such as hydroxyl
      radicals and ferryl-oxo species by combining ab initio molecular dynamics
      simulations and an MFEP search method. Along the MFEPs, representative free
      energy profiles of the Fenton reaction were elucidated. On the basis of the free
      energy profiles, we revealed that the reaction producing ferryl-oxo species from
      Fenton's reagent is more energetically favorable than that yielding a free
      hydroxyl radical, by 24.4 kcal mol(-1), which indicates that the ferryl-oxo
      species is the primary oxidizing agent in reactions of Fenton's reagent.
      Moreover, we clarified that the ferryl-oxo species is favorably formed via a two
      step reaction pathway, which reaches the product through a dihydroxyiron(IV)
      intermediate. The energetics charting the free-energy profiles provided valuable
      information for a comprehensive understanding of Fenton reactions. We concluded
      that a ferryl-oxo species produced from Fenton's reagent serves as the primary
      oxidizing agent in the Fenton reaction.

PMID- 23148729
TI  - Field emission properties of gold nanoparticle-decorated ZnO nanopillars.
AB  - The structural and optoelectronic properties of ZnO nanopillars (ZnO-NPs) grown
      on Si substrates by the vapor transport deposition method were investigated. In
      particular, by varying the deposition duration and hence the morphology of the
      vertically aligned ZnO-NPs, the resultant field emission characteristics were
      systematically compared. In addition to identifying the advantageous field
      emission properties exhibited in the pencil-like ZnO-NPs, we observed that by
      adhering Au nanoparticles on the surface of the ZnO-NPs the turn-on field and the
      maximum current density can be drastically improved from 3.15 V/MUm and 0.44
      mA/cm(2) at 5 V/MUm for the best ZnO-NPs to 2.65 V/MUm and 2.11 mA/cm(2) at 5
      V/MUm for Au/ZnO-NPs, respectively. The enhancement of field emission
      characteristics that resulted from Au-nanoparticle decoration is discussed on the
      basis of charge-transfer-induced band structure modifications.

PMID- 23148730
TI  - Uniform graphene quantum dots patterned from self-assembled silica nanodots.
AB  - Graphene dots precisely controlled in size are interesting in nanoelectronics due
      to their quantum optical and electrical properties. However, most graphene
      quantum dot (GQD) research so far has been performed based on flake-type graphene
      reduced from graphene oxides. Consequently, it is extremely difficult to isolate
      the size effect of GQDs from the measured optical properties. Here, we report the
      size-controlled fabrication of uniform GQDs using self-assembled block copolymer
      (BCP) as an etch mask on graphene films grown by chemical vapor deposition (CVD).
      Electron microscope images show that as-prepared GQDs are composed of mono- or
      bilayer graphene with diameters of 10 and 20 nm, corresponding to the size of BCP
      nanospheres. In the measured photoluminescence (PL) spectra, the emission peak of
      the GQDs on the SiO(2) substrate is shown to be at ~395 nm. The fabrication of
      GQDs was supported by the analysis of the Raman spectra and the observation of PL
      spectra after each fabrication step. Additionally, oxygen content in the GQDs is
      rationally controlled by additional air plasma treatment, which reveals the
      effect of oxygen content to the PL property.

PMID- 23148731
TI  - Tolerability, pharmacokinetics, and bioequivalence of the tablet and syrup
      formulations of lacosamide in plasma, saliva, and urine: saliva as a surrogate of
      pharmacokinetics in the central compartment.
AB  - PURPOSE: To test for bioequivalence of 200 mg lacosamide oral tablet and syrup
      formulations. Additional objectives were to compare the pharmacokinetic profile
      of lacosamide in saliva and plasma, and to evaluate its tolerability. METHODS:
      This open-label, randomized, two-way crossover trial was conducted in 16 healthy
      Caucasian male participants in Germany. The bioequivalence of 200 mg lacosamide
      tablet and syrup was evaluated using plasma to determine maximum measured
      concentration (C(max)) and area under the curve from zero to the last time point
      (AUC)(0-tz). Plasma and saliva samples for evaluation of pharmacokinetic
      parameters of lacosamide and the major metabolite O-desmethyl lacosamide (SPM
      12809) were taken over 15 time points (0.5-72 h) and used to statistically
      compare bioavailability of the two. Urine samples were collected predose and over
      five time points (0-48 h) to evaluate the cumulative amount of unchanged drug and
      metabolite. KEY FINDINGS: Lacosamide median time to reach C(max) (t(max)) was 1 h
      for tablet and 0.5 h for syrup in plasma and saliva. Mean terminal half life
      (t(1/2)) for tablet and syrup was 12.5 and 12.4 h in plasma, and 13.1 and 13.3 h
      in saliva, respectively. Tablet and syrup mean plasma AUC(0-tz) was 84.5 and 83.3
      MUg/mL*h, respectively. Mean AUC(0-tz) in saliva was 93.2 MUg/mL*h for tablet and
      syrup. Mean C(max) for tablet was 5.26 MUg/mL in plasma and 5.63 MUg/mL in
      saliva. Syrup mean C(max) was 5.14 and 8.32 MUg/mL in plasma and saliva,
      respectively. Within 2 h of syrup administration, elevated lacosamide
      concentration in saliva compared to plasma was observed. The ratio of lacosamide
      syrup to tablet was 0.98 for C(max) and 0.99 for AUC(0-tz) in plasma, and 1.00
      for AUC((0-tz)) in saliva; the 90% confidence intervals (CIs) for these
      parameters were within the range of 0.80-1.25, which meets accepted
      bioequivalence criteria. The syrup-to-tablet ratio for C(max) in saliva was 1.48,
      and the 90% CIs exceeded the accepted upper boundary for bioequivalence (1.32
      1.66). Both formulations were well tolerated. Metabolite concentration versus
      time profiles for saliva were similar to plasma following tablet and syrup
      administration. SIGNIFICANCE: The tablet and syrup formulations of lacosamide 200
      mg were bioequivalent and well tolerated. Saliva samples were demonstrated to be
      a suitable surrogate to evaluate lacosamide tablet pharmacokinetics in the
      central compartment. Due to residual syrup in the buccal cavity, limitations
      exist when using saliva to evaluate the pharmacokinetics of lacosamide syrup <2 h
      after administration.

PMID- 23148732
TI  - Expression of AQP5 and AQP8 in human colorectal carcinoma and their clinical
      significance.
AB  - BACKGROUND: The aquaporins (AQPs) are a family of small membrane transport
      proteins whose overexpression has been implicated in tumorigenesis. However, the
      expression of AQP5 and AQP8 in colorectal cancer and the clinical significance
      remain unexplored. This study aimed to detect the expression of AQP5 and AQP8 in
      clinical samples of colorectal cancer and analyze the correlations of their
      expression with the clinicopathological features of colorectal cancer. METHODS:
      Forty pairs of colorectal cancer tissue and paraneoplastic normal tissue were
      obtained at the time of surgery from patients with colorectal cancer. The
      expression of AQP5 and AQP8 was detected by immunohistochemical staining and
      reverse transcriptase polymerase chain reaction. RESULTS: AQP5 was mainly
      expressed in colorectal carcinoma cells and barely expressed in paraneoplastic
      normal tissues. By contrast, AQP8 was mainly expressed in paraneoplastic normal
      tissues and barely expressed in colorectal carcinoma cells. AQP5 expression was
      not significantly associated with the sex or age of the patient with colorectal
      cancer (P>0.05), but was closely associated with the differentiation, tumor-nodes
      metastasis stage and distant lymph node metastasis of colorectal carcinoma
      (P<0.05). CONCLUSIONS: AQP5 might be a novel prognostic biomarker for patients
      with colorectal cancer.

PMID- 23148733
TI  - Efficient [WO4](2-)-catalyzed chemical fixation of carbon dioxide with 2
      aminobenzonitriles to quinazoline-2,4(1H,3H)-diones.
AB  - A simple monomeric tungstate, TBA(2)[WO(4)] (I, TBA = tetra-n-butylammonium),
      could act as an efficient homogeneous catalyst for chemical fixation of CO(2)
      with 2-aminobenzonitriles to quinazoline-2,4(1H,3H)-diones. Various kinds of
      structurally diverse 2-aminobenzonitriles could be converted into the
      corresponding quinazoline-2,4(1H,3H)-diones in high yields at atmospheric
      pressure of CO(2). Reactions of inactive 2-amino-4-chlorobenzonitrile and 2-amino
      5-nitrobenzonitrile at 2 MPa of CO(2) also selectively proceeded. The present
      system was applicable to a g-scale reaction of 2-amino-5-fluorobenzonitrile (10
      mmol scale) with CO(2) and 1.69 g of analytically pure quinazoline-2,4(1H,3H)
      dione could be isolated. In this case, the turnover number reached up to 938 and
      the value was the highest among those reported for base-mediated systems so far.
      NMR spectroscopies showed formation of the corresponding carbamic acid through
      the simultaneous activation of both 2-aminobenzonitirile and CO(2) by I. Kinetic
      and computational studies revealed that I plays an important role in conversion
      of the carbamic acid into the product.

PMID- 23148734
TI  - Specialist prescribing of psychotropic drugs to older persons in Sweden--a
      register-based study of 188,024 older persons.
AB  - BACKGROUND: The situation for older persons with mental disorders other than
      dementia disorders has scarcely been studied. The older population is increasing
      worldwide and along with this increase the prevalence of mental disorders will
      also rise. The treatment of older persons with mental disorders entails complex
      challenges, with drugs constituting the major medical treatment. Knowledge of
      geriatric psychiatry is essential for providing older persons with appropriate
      treatment and care. This study aimed to evaluate the prescription of drugs for
      mental disorders to older persons (>= 65) in Sweden, focused on the medical
      specialties of the prescribing physicians. METHODS: Data concerning drug
      treatment for older persons from 2006 to 2008 was gathered from the Swedish
      Prescribed Drug Register. Mental disorders, defined as affective, psychotic and
      anxiety disorders (ICD-10 F20-42) were evaluated in order to identify associated
      drugs. Included was a total of 188,024 older individuals, who collectively filled
      2,013,079 prescriptions for the treatment of mental disorders. Descriptive
      analyses were performed, including frequency distribution and 95% CI. The
      competence of the prescribers was analyzed by subdividing them into five groups:
      geriatricians, psychiatrists, general practitioners (GPs), other specialists, and
      physicians without specialist education. RESULTS: GPs represented the main
      prescribers, whereas geriatricians and psychiatrists rarely prescribed drugs to
      older persons. Benzodiazepines and tricyclic antidepressants were the most
      commonly prescribed drugs. Women were prescribed drugs from geriatricians and
      psychiatrists to a greater extent than men. CONCLUSIONS: This study examined the
      prescription of psychotropic drugs to older persons. Physicians specialized in
      older persons' disorders and mental health were rarely the prescribers of these
      drugs. Contrary to clinical guidelines, benzodiazepines and tricyclic
      antidepressants were commonly prescribed to older persons, emphasizing the need
      for continuous examination of pharmaceutical treatment for older persons. The
      results indicate a future need of more specialists in geriatrics and psychiatry.

PMID- 23148735
TI  - Homogeneous nucleation of methane hydrates: unrealistic under realistic
      conditions.
AB  - Methane hydrates are ice-like inclusion compounds with importance to the oil and
      natural gas industry, global climate change, and gas transportation and storage.
      The molecular mechanism by which these compounds form under conditions relevant
      to industry and nature remains mysterious. To understand the mechanism of methane
      hydrate nucleation from supersaturated aqueous solutions, we performed
      simulations at controlled and realistic supersaturation. We found that critical
      nuclei are extremely large and that homogeneous nucleation rates are extremely
      low. Our findings suggest that nucleation of methane hydrates under these
      realistic conditions cannot occur by a homogeneous mechanism.

PMID- 23148737
TI  - Gastrointestinal symptoms and psychological well-being in patients with
      microscopic colitis.
AB  - OBJECTIVE: Microscopic colitis (MC) and irritable bowel syndrome (IBS) are both
      gastrointestinal disorders with female predominance that affect well-being.
      Autoantibodies against gonadotropin-releasing hormone (GnRH) have recently been
      detected in IBS patients. The purpose of this study was to compare
      gastrointestinal symptoms and well-being in MC female outpatients, with or
      without coexisting IBS-like symptoms, and to examine the prevalence of GnRH
      antibodies in these patients. MATERIAL AND METHODS: Women with biopsy-verified
      MC, at any outpatient clinic of the Departments of Gastroenterology, Skane,
      between 2002 and 2010 were invited to participate in the study. The
      questionnaires Gastrointestinal Symptom Rating Scale (GSRS), Psychological
      General Well-being Index (PGWB), Visual Analogue Scale for Irritable Bowel
      Syndrome (VAS-IBS), and Rome III were answered and blood samples collected.
      Autoantibodies (IgG, IgA, and IgM) against GnRH and GnRH-R (extracellular peptide
      of receptor) were determined by an enzyme-linked immunosorbent assay. RESULTS:
      Altogether, 158 (66%) of 240 invited patients with MC were recruited to the
      study. Of these, 133 (55%) patients also accepted to provide blood samples.
      Patients with IBS-like symptoms (55%) experienced more symptoms and worse
      psychological well-being in all dimensions in GSRS and PGWB, and in all symptoms
      but constipation in VAS-IBS compared to patients without IBS symptoms. Only a
      minority of patients expressed antibodies against GnRH or GnRH-R, which did not
      differ between groups. CONCLUSIONS: MC patients fulfilling criteria for IBS
      experience more gastrointestinal symptoms and worse psychological well-being than
      those who do not. Autoantibodies against GnRH or GnRH-R are not frequently
      observed in MC patients.

PMID- 23148736
TI  - A randomized trial of 7-day doripenem versus 10-day imipenem-cilastatin for
      ventilator-associated pneumonia.
AB  - INTRODUCTION: The aim of this study was to compare a 7-day course of doripenem to
      a 10-day course of imipenem-cilastatin for ventilator-associated pneumonia (VAP)
      due to Gram-negative bacteria. METHODS: This was a prospective, double-blinded,
      randomized trial comparing a fixed 7-day course of doripenem one gram as a four
      hour infusion every eight hours with a fixed 10-day course of imipenem-cilastatin
      one gram as a one-hour infusion every eight hours (April 2008 through June 2011).
      RESULTS: The study was stopped prematurely at the recommendation of the
      Independent Data Monitoring Committee that was blinded to treatment arm
      assignment and performed a scheduled review of data which showed signals that
      were close to the pre-specified stopping limits. The final analyses included 274
      randomized patients. The clinical cure rate at the end of therapy (EOT) in the
      microbiological intent-to-treat (MITT) population was numerically lower for
      patients in the doripenem arm compared to the imipenem-cilastatin arm (45.6%
      versus 56.8%; 95% CI, -26.3% to 3.8%). Similarly, the clinical cure rate at EOT
      was numerically lower for patients with Pseudomonas aeruginosa VAP, the most
      common Gram-negative pathogen, in the doripenem arm compared to the imipenem
      cilastatin arm (41.2% versus 60.0%; 95% CI, -57.2 to 19.5). All cause 28-day
      mortality in the MITT group was numerically greater for patients in the doripenem
      arm compared to the imipenem-cilastatin arm (21.5% versus 14.8%; 95% CI, -5.0 to
      18.5) and for patients with P. aeruginosa VAP (35.3% versus 0.0%; 95% CI, 12.6 to
      58.0). CONCLUSIONS: Among patients with microbiologically confirmed late-onset
      VAP, a fixed 7-day course of doripenem was found to have non-significant higher
      rates of clinical failure and mortality compared to a fixed 10-day course of
      imipenem-cilastatin. Consideration should be given to treating patients with VAP
      for more than seven days to optimize clinical outcome. TRIAL REGISTRATION:
      ClinicalTrials.gov: NCT00589693.

PMID- 23148739
TI  - A 63-year-old woman presenting with a synovial sarcoma of the hand: a case
      report.
AB  - INTRODUCTION: Synovial sarcoma is a high-grade, soft-tissue sarcoma that most
      frequently is located in the vicinity of joints, tendons or bursae, although it
      can also be found in extra-articular locations. Most patients with synovial
      sarcoma of the hand are young and have a poor prognosis, as these tumors are
      locally aggressive and are associated with a relatively high metastasis rate.
      According to the literature, local recurrence and/or metastatic disease is found
      in nearly 80% of patients. Current therapy comprises surgery, systemic and limb
      perfusion chemotherapy, and radiotherapy. However, the 5-year survival rate is
      estimated to be only around 27% to 55%. Moreover, most authors agree that
      synovial sarcoma is one of the most commonly misdiagnosed malignancies of soft
      tissues because of their slow growing pattern, benign radiographic appearance,
      ability to change size, and the fact that they may elicit pain similar to that
      caused by common trauma. CASE PRESENTATION: We describe an unusual case of a
      large synovial sarcoma of the hand in a 63-year-old Caucasian woman followed for
      12 years by a multidisciplinary team. In addition, a literature review of the
      most pertinent aspects of the epidemiology, diagnosis, treatment and prognosis of
      these patients is presented. CONCLUSION: Awareness of this rare tumor by anyone
      dealing with hand pathology can hasten diagnosis, and this, in turn, can
      potentially increase survival. Therefore, a high index of suspicion for this
      disease should be kept in mind, particularly when evaluating young people, as
      they are the most commonly affected group.

PMID- 23148741
TI  - Condensation and polymerization of supersaturated monomer vapor.
AB  - Initiated chemical vapor deposition (iCVD) of poly(glycidyl methacrylate) from
      supersaturated monomer vapor is reported. Rapid film growth rates, up to 600
      nm/min, were observed. Films grown from supersaturated monomer exhibited distinct
      surface undulations. The temporal evolution of surface features during film
      growth was studied and is explained by monomer condensation followed by droplet
      coalescence and film growth. High droplet densities were observed at the early
      times and are attributed to rapid polymerization of monomer within condensed
      liquid nuclei. Droplet nucleation resulting in surface undulations can be avoided
      by first depositing a thin, cross-linked film from ethylene glycol diacrylate
      monomer followed by deposition of supersaturated monomer vapors.

PMID- 23148740
TI  - Prevalence of dental caries among a cohort of preschool children living in
      Gampaha district, Sri Lanka: a descriptive cross sectional study.
AB  - BACKGROUND: Dental caries among young children are a global problem. Scant
      attention is paid towards primary teeth, leading to high prevalence of dental
      caries. There are only few studies done in Sri Lanka, addressing oral hygiene
      among preschool children. Scientific evidence is in need to persuade authorities
      to establish a programme promoting oral hygiene among preschool children.
      METHODS: A descriptive cross sectional study was conducted in Ragama Medical
      officer of Health area. Consecutive children between 2 - 5 years of age,
      attending child welfare clinics were recruited for the study. Practices related
      to dental hygiene and socio-economic characteristics were obtained using an
      interviewer administered questionnaire. Mouth was examined for evidence of dental
      caries. Data collection and examination were done by two doctors who were trained
      for this purpose. The data were analysed using SSPS version 16. RESULTS: Total of
      410 children were included. None had a routine visits to a dentist. Practices
      related to tooth brushing were satisfactory. Prevalence of dental caries
      gradually increased with age to reach 68.8% by 5 years. Mean total decayed
      extracted-filled (deft) score for the whole sample was 1.41 and Significant
      caries index (SIC) was 4.09. Decayed tooth were the main contributor for the deft
      score and Care index was only 1.55. Girls had a significantly higher prevalence
      of caries than boys. CONCLUSIONS: Dental care provided for Sri Lankan preschool
      children appears to be unsatisfactory as prevalence of dental caries among this
      cohort of preschool children was very high. There is an urgent need to improve
      dental care facilities for Sri Lankan preschool children.

PMID- 23148742
TI  - Parameter variability and distributional assumptions in the diffusion model.
AB  - If the diffusion model (Ratcliff & McKoon, 2008) is to account for the relative
      speeds of correct responses and errors, it is necessary that the components of
      processing identified by the model vary across the trials of a task. In standard
      applications, the rate at which information is accumulated by the diffusion
      process is assumed to be normally distributed across trials, the starting point
      for the process is assumed to be uniformly distributed across trials, and the
      time taken by processes outside the diffusion process is assumed to be uniformly
      distributed. With the studies in this article, I explore the consequences of
      alternative assumptions about the distributions, using a wide range of parameter
      values. The model with the standard assumptions was fit to predictions generated
      with the alternative assumptions, and the results showed that the recovered
      parameter values matched the values used to generate the predictions with only a
      few exceptions. These occurred when parameter combinations were extreme and when
      a skewed distribution (exponential) of nondecision times was used. The conclusion
      is that the standard model is robust to moderate changes in the across-trial
      distributions of parameter values.

PMID- 23148743
TI  - Morphometrical diagnosis of the malaria vectors Anopheles cruzii, An. homunculus
      and An. bellator.
AB  - BACKGROUND: Anopheles (Kerteszia) cruzii is a primary vector of Plasmodium
      parasites in Brazil's Atlantic Forest. Adult females of An. cruzii and An.
      homunculus, which is a secondary malaria vector, are morphologically similar and
      difficult to distinguish when using external morphological characteristics only.
      These two species may occur syntopically with An. bellator, which is also a
      potential vector of Plasmodium species and is morphologically similar to An.
      cruzii and An. homunculus. Identification of these species based on female
      specimens is often jeopardised by polymorphisms, overlapping morphological
      characteristics and damage caused to specimens during collection. Wing geometric
      morphometrics has been used to distinguish several insect species; however, this
      economical and powerful tool has not been applied to Kerteszia species. Our
      objective was to assess wing geometry to distinguish An. cruzii, An. homunculus
      and An. bellator. METHODS: Specimens were collected in an area in the Serra do
      Mar hotspot biodiversity corridor of the Atlantic Forest biome (Cananeia
      municipality, State of Sao Paulo, Brazil). The right wings of females of An.
      cruzii (n= 40), An. homunculus (n= 50) and An. bellator (n= 27) were
      photographed. For each individual, 18 wing landmarks were subjected to standard
      geometric morphometrics. Discriminant analysis of Procrustean coordinates was
      performed to quantify wing shape variation. RESULTS: Individuals clustered into
      three distinct groups according to species with a slight overlap between
      representatives of An. cruzii and An. homunculus. The Mahalanobis distance
      between An. cruzii and An. homunculus was consistently lower (3.50) than that
      between An. cruzii and An. bellator (4.58) or An. homunculus and An. bellator
      (4.32). Pairwise cross-validated reclassification showed that geometric
      morphometrics is an effective analytical method to distinguish between An.
      bellator, An. cruzii and An. homunculus with a reliability rate varying between
      78-88%. Shape analysis revealed that the wings of An. homunculus are narrower
      than those of An. cruzii and that An. bellator is different from both of the
      congeneric species. CONCLUSION: It is possible to distinguish among the vectors
      An. cruzii, An. homunculus and An. bellator based on female wing characteristics.

PMID- 23148744
TI  - Presumptive bacterial translocation in horses with strangulating small intestinal
      lesions requiring resection and anastomosis.
AB  - OBJECTIVE: To document whether presumptive bacterial translocation (PBT) occurs
      in horses with small intestinal strangulation (SIS). DESIGN: Prospective clinical
      cohort study. SETTING: University tertiary care facility. ANIMALS: Thirty-six
      adult horses with SIS (clinical cases) and 10 adult horses without
      gastrointestinal disease (control cases). INTERVENTIONS: Sterile collection and
      bacterial culture of samples from peripheral venous blood, mesenteric venous
      blood, mesenteric lymphatic tissue, and intestinal aspirates from horses with SIS
      and control horses without gastrointestinal disease. MEASUREMENTS AND MAIN
      RESULTS: Five of 36 (13.8%) horses with SIS had at least 1 sample yield a
      positive result. Shorter SIS bowel segments were more likely to yield a positive
      culture result. (P < 0.01). Two of 10 of control horses had positive culture
      results with different bacterial species identified compared to horses with SIS.
      Antimicrobial usage did not influence bacterial culture status (P = 0.31). There
      were no differences between culture-positive and culture-negative horses with SIS
      regarding admission, clinical, or clinicopathologic variables. CONCLUSIONS: PBT
      occurs in normal horses and in horses with SIS. Bacterial genera differed between
      groups. A low incidence of PBT occurs in horses with SIS suggesting postoperative
      morbidity in some cases may be due to other factors.

PMID- 23148745
TI  - Fabrication of a novel cholic acid modified OPE-based fluorescent film and its
      sensing performances to inorganic acids in acetone.
AB  - A self-assembled monolayer (SAM)-based fluorescent film was designed and prepared
      by chemical immobilization of a novel oligo(p-phenylene- ethynylene) (OPE) with
      cholic acid moieties at the ends of its side chains (Film 1). As a control, a
      similar film, Film 2, of which OPE brings no side chains, was also prepared. The
      structures of the films were characterized by contact angle, XPS, ATR-IR and
      fluorescence measurements. Fluorescence studies revealed that the emission of
      Film 1 is sensitive to the presence of trace amount of some inorganic acids in
      acetone, such as HCl, H(2)SO(4), HNO(3), and H(3)PO(4), etc., whereas the acids
      as studied showed little effect on the emission of Film 2. The difference in the
      sensing performances of the two films have been rationalized by considering
      presence or absence of a possible cavity, a substructure appearing above the OPE
      adlayer which is something like a dimer of cholic acid (CholA) formed at specific
      environment.

PMID- 23148746
TI  - Dendritic cells: an immunotherapy coming of age.

PMID- 23148747
TI  - Dendritic cells: active and passive players in therapy of human diseases.

PMID- 23148748
TI  - Potential applications for plasmacytoid dendritic cells in cancer immunotherapy.

PMID- 23148749
TI  - How effective could laser-based approaches be in assisting dendritic cell
      immunotherapy?

PMID- 23148751
TI  - Results of a Phase II clinical trial with Id-protein-loaded dendritic cell
      vaccine in multiple myeloma: encouraging or discouraging?
AB  - Recently gained insight into the role of dendritic cells (DCs) as APCs has
      attracted the attention of many researchers who hope to use them as a tool in
      immunotherapy for the induction of tumor-specific immunity in cancer settings.
      Despite high expectations, in multiple myeloma patients the results of DC-based
      vaccines in terms of clinical response have been disappointing. The findings of
      Zahradova et al. in a Phase II clinical trial with multiple myeloma patients
      corroborated these results. Although no clinical responses were observed, the
      investigators induced immunity after vaccination with Id-protein-loaded DC
      vaccine in some patients. These immunological results showed a trend towards a
      longer duration of stable disease in those patients that received the
      vaccination. Moreover, this study showed that Id-protein-loaded DC vaccines are
      safe and nontoxic and that they are able to induce immunity in some patients.
      Therefore, standardization of vaccination protocols appears to be the key to
      achieving a better clinical outcome.

PMID- 23148752
TI  - Dendritic cell-based tumor vaccinations in epithelial ovarian cancer: a
      systematic review.
AB  - After decades of extensive research, epithelial ovarian cancer still remains a
      lethal disease. Multiple new studies have reported that the immune system plays a
      critical role in the growth and spread of ovarian carcinoma. This review
      summarizes the development of dendritic cell (DC) vaccinations specific for
      ovarian cancer. So far, DC-based vaccines have induced effective antitumor
      responses in animal models, but only limited results from human clinical trials
      are available. Although DC-based immunotherapy has proven to be clinically safe
      and efficient at inducing tumor-specific immune responses, its clear role in the
      therapy of ovarian cancer still needs to be clarified. The relatively
      disappointing low-response rates in early clinical trials point to the need for
      the development of more effective and personalized DC-based anticancer vaccines.
      This article reviews the basic mechanisms, limitations and future directions of
      DC-based anti-ovarian cancer vaccine development.

PMID- 23148753
TI  - Dendritic cell-based immunotherapy in mesothelioma.
AB  - Mesothelioma is a rare thoracic malignancy with a dismal prognosis. Current
      treatment options are scarce and clinical outcomes are rather disappointing. Due
      to the immunogenic nature of mesothelioma, several studies have investigated
      immunotherapeutic strategies to improve the prognosis of patients with
      mesothelioma. In the last decade, progress in knowledge of the modulation of the
      immune system to attack the tumor has been remarkable, but the optimal strategy
      for immunotherapy has yet to be unraveled. Because of their potent antigen
      presenting capacity, dendritic cells are acknowledged as a promising agent in
      immunotherapeutic approaches in a number of malignancies. This review gives an
      update and provides a future perspective in which immunotherapy may improve the
      outcome of mesothelioma therapy.

PMID- 23148754
TI  - Dendritic cell immunotherapy in soft tissue sarcoma.
AB  - Soft tissue sarcomas represent a rare but diverse family of tumors affecting
      patients of all ages. Conventional chemotherapy rarely eradicates metastatic
      disease and newer targeted agents are successful in only very specific histologic
      subgroups. Therefore, scientists and clinicians are investigating immunotherapy
      techniques, primarily involving cellular immunity focused on the T-cell response
      to tumor antigens. In both animal models and human sarcoma trials, dendritic
      cells have been shown to induce an effective antitumor immune response.
      Radiotherapy, particularly when delivered in a hypofractionated manner prior to
      sarcoma excision, may potentiate the function of the dendritic cells through the
      induction of apoptosis. The synergistic effect may carry over to other cancer
      types and warrants further multidisciplinary investigation.

PMID- 23148755
TI  - Dendritic cell-based vaccination for renal cell carcinoma: challenges in clinical
      trials.
AB  - After decades of research, dendritic cell (DC)-based vaccines for renal cell
      carcinoma have progressed from preclinical rodent models and safety assessments
      to Phase I/II clinical trials. DC vaccines represent a promising therapy that has
      produced measurable immunological responses and prolonged survival rates.
      However, there is still much room to improve in terms of therapeutic efficacy.
      The key issues that affect the efficiency and reliability of DC therapy include
      the selection of patients who will respond best to treatment, the proper
      preparation and administration of DC vaccines, and a combination of DC
      vaccination with other immune-enhancing therapies (e.g., removal of Tregs, CTLA-4
      blockade and lymphodepletion). Additional antiangiogenic agents will hopefully
      lead to greater survival benefits for patients in early disease stages. This
      review focuses on the different approaches of DC-based vaccination against renal
      cell carcinoma and potential strategies to enhance the efficacy of DC
      vaccination.

PMID- 23148756
TI  - Evolution of cellular immunotherapy: from allogeneic transplant to dendritic cell
      vaccination as treatment for multiple myeloma.
AB  - The promise of cellular therapy as treatment for multiple myeloma is highlighted
      by the observation that allogeneic transplantation results in durable remissions
      in a subset of patients. The potency of the graft-versus-myeloma effect is
      supported by the decreased risk of relapse seen in patients with graft-versus
      host disease and disease response following donor lymphocyte infusions. However,
      the lack of specificity of the alloreactive lymphocytes limits their therapeutic
      efficacy and results in significant treatment-related morbidity and mortality. A
      major area of investigation is the development of cancer vaccines to generate
      myeloma-specific immunity that selectively targets malignant cells while
      minimizing toxicity to normal tissues. Critical elements required to develop an
      effective vaccine strategy involve the identification of myeloma-associated
      antigens, enhancement of antigen presentation, and reversing the
      immunosuppressive milieu induced by the disease. Dendritic cells are potent APCs
      that represent an ideal platform for vaccination. Strategies for vaccine design
      include the loading of individual antigens as well as the use of whole tumor
      cells as a source of myeloma antigens. Vaccination has been examined in the
      postautologous transplant setting in which disease cytoreduction and depletion of
      Tregs is associated with enhanced vaccine response. Recent efforts have also
      included exploration of immune modulatory agents that target inhibitory pathways
      to enhance vaccine response and create a more durable antitumor immunity.

PMID- 23148758
TI  - Dendritic cell therapy for Type 1 diabetes suppression.
AB  - While dendritic cell-based therapy is a clinical reality for human malignancies,
      until now, some conceptual concerns have served to delay its consideration to
      treat human autoimmune diseases, even in light of almost two decades' worth of
      overwhelmingly supportive preclinical animal studies. This article provides an
      overview of the development of dendritic cell-based therapy for Type 1 diabetes
      mellitus, given that this is the best-studied autoimmune disorder and that there
      is a good understanding of the underlying immunology. This article also
      highlights data from the authors' pioneering Phase I clinical trial with
      tolerogenic dendritic cells, which hopes to motivate the clinical translation of
      other dendritic cell-based approaches, to one or more carefully selected Type 1
      diabetic patient populations.

PMID- 23148757
TI  - Plasmacytoid dendritic cells and immunotherapy in multiple sclerosis.
AB  - Plasmacytoid dendritic cells (pDCs) are specialized APCs implicated in the
      pathogenesis of many human diseases. Compared with other peripheral blood
      mononuclear cells, pDCs express a high level of TLR9, which recognizes viral DNA
      at the initial phase of viral infection. Upon stimulation, these cells produce
      large amounts of type I interferon and other proinflammatory cytokines and are
      able to prime T lymphocytes. Thus, pDCs regulate innate and adaptive immune
      responses. This article reviews select aspects of pDC biology relevant to the
      disease pathogenesis and immunotherapy in multiple sclerosis. Many unresolved
      questions remain in this area, promising important future discoveries in pDC
      research.

PMID- 23148760
TI  - Sedentary behaviours and its association with bone mass in adolescents: the
      HELENA Cross-Sectional Study.
AB  - BACKGROUND: We aimed to examine whether time spent on different sedentary
      behaviours is associated with bone mineral content (BMC) in adolescents, after
      controlling for relevant confounders such as lean mass and objectively measured
      physical activity (PA), and if so, whether extra-curricular participation in
      osteogenic sports could have a role in this association. METHODS: Participants
      were 359 Spanish adolescents (12.5-17.5 yr, 178 boys,) from the HELENA-CSS (2006
      07). Relationships of sedentary behaviours with bone variables were analysed by
      linear regression. The prevalence of low BMC (at least 1SD below the mean) and
      time spent on sedentary behaviours according to extracurricular sport
      participation was analysed by Chi-square tests. RESULTS: In boys, the use of
      internet for non-study was negatively associated with whole body BMC after
      adjustment for lean mass and moderate to vigorous PA (MVPA). In girls, the time
      spent studying was negatively associated with femoral neck BMC. Additional
      adjustment for lean mass slightly reduced the negative association between time
      spent studying and femoral neck BMC. The additional adjustment for MVPA did not
      change the results at this site. The percentage of girls having low femoral neck
      BMC was significantly smaller in those participating in osteogenic sports (>= 3
      h/week) than in the rest, independently of the cut-off selected for the time
      spent studying. CONCLUSIONS: The use of internet for non-study (in boys) and the
      time spent studying (in girls) are negatively associated with whole body and
      femoral neck BMC, respectively. In addition, at least 3 h/week of extra
      curricular osteogenic sports may help to counteract the negative association of
      time spent studying on bone health in girls.

PMID- 23148761
TI  - Mechanical performance of endodontic restorations with prefabricated posts:
      sensitivity analysis of parameters with a 3D finite element model.
AB  - Many studies have investigated the effect of different parameters of the
      endodontically restored tooth on its final strength, using in vitro tests and
      model simulations. However, the differences in the experimental set-up or
      modelling conditions and the limited number of parameters studied in each case
      prevent us from obtaining clear conclusions about the relative importance of each
      parameter. In this study, a validated 3D biomechanical model of the restored
      tooth was used for an exhaustive sensitivity analysis. The individual influence
      of 20 different parameters on the mechanical performance of an endodontic
      restoration with prefabricated posts was studied. The results bring up the
      remarkable importance of the loading angle on the final restoration strength.
      Flexural loads are more critical than compressive or tensile loads. Young's
      modulus of the post and its length and diameter are the most influential
      parameters for strength, whereas other parameters such as ferrule geometry or
      core and crown characteristics are less significant. 

PMID- 23148762
TI  - Using Audience Response Technology to provide formative feedback on pharmacology
      performance for non-medical prescribing students--a preliminary evaluation.
AB  - BACKGROUND: The use of anonymous audience response technology (ART) to actively
      engage students in classroom learning has been evaluated positively across
      multiple settings. To date, however, there has been no empirical evaluation of
      the use of individualised ART handsets and formative feedback of ART scores. The
      present study investigates student perceptions of such a system and the
      relationship between formative feedback results and exam performance. METHODS:
      Four successive cohorts of Non-Medical Prescribing students (n=107) had access to
      the individualised ART system and three of these groups (n=72) completed a
      questionnaire about their perceptions of using ART. Semi-structured interviews
      were carried out with a purposive sample of seven students who achieved a range
      of scores on the formative feedback. Using data from all four cohorts of
      students, the relationship between mean ART scores and summative pharmacology
      exam score was examined using a non-parametric correlation. RESULTS:
      Questionnaire and interview data suggested that the use of ART enhanced the
      classroom environment, motivated students and promoted learning. Questionnaire
      data demonstrated that students found the formative feedback helpful for
      identifying their learning needs (95.6%), guiding their independent study
      (86.8%), and as a revision tool (88.3%). Interviewees particularly valued the
      objectivity of the individualised feedback which helped them to self-manage their
      learning. Interviewees' initial anxiety about revealing their level of
      pharmacology knowledge to the lecturer and to themselves reduced over time as
      students focused on the learning benefits associated with the feedback.A
      significant positive correlation was found between students' formative feedback
      scores and their summative pharmacology exam scores (Spearman's rho = 0.71,
      N=107, p<.01). CONCLUSIONS: Despite initial anxiety about the use of
      individualised ART units, students rated the helpfulness of the individualised
      handsets and personalised formative feedback highly. The significant correlation
      between ART response scores and student exam scores suggests that formative
      feedback can provide students with a useful reference point in terms of their
      level of exam-readiness.

PMID- 23148763
TI  - The evolution of global health teaching in undergraduate medical curricula.
AB  - BACKGROUND: Since the early 1990s there has been a burgeoning interest in global
      health teaching in undergraduate medical curricula. In this article we trace the
      evolution of this teaching and present recommendations for how the discipline
      might develop in future years. DISCUSSION: Undergraduate global health teaching
      has seen a marked growth over the past ten years, partly as a response to student
      demand and partly due to increasing globalization, cross-border movement of
      pathogens and international migration of health care workers. This teaching has
      many different strands and types in terms of topic focus, disciplinary
      background, the point in medical studies in which it is taught and whether it is
      compulsory or optional. We carried out a survey of medical schools across the
      world in an effort to analyse their teaching of global health. Results indicate
      that this teaching is rising in prominence, particularly through global health
      elective/exchange programmes and increasing teaching of subjects such as
      globalization and health and international comparison of health systems. Our
      findings indicate that global health teaching is moving away from its previous
      focus on tropical medicine towards issues of more global relevance. We suggest
      that there are three types of doctor who may wish to work in global health - the
      'globalised doctor', 'humanitarian doctor' and 'policy doctor' - and that each of
      these three types will require different teaching in order to meet the required
      competencies. This teaching needs to be inserted into medical curricula in
      different ways, notably into core curricula, a special overseas doctor track,
      optional student selected components, elective programmes, optional intercalated
      degrees and postgraduate study. SUMMARY: We argue that teaching of global health
      in undergraduate medical curricula must respond to changing understandings of the
      term global health. In particular it must be taught from the perspective of more
      disciplines than just biomedicine, in order to reflect the social, political and
      economic causes of ill health. In this way global health can provide valuable
      training for all doctors, whether they choose to remain in their countries of
      origin or work abroad.

PMID- 23148764
TI  - Size-dependent deformation of nanocrystalline Pt nanopillars.
AB  - We report the synthesis, mechanical properties, and deformation mechanisms of
      polycrystalline, platinum nanocylinders of grain size d = 12 nm. The number of
      grains across the diameter, D/d, was varied from 5 to 80 and 1.5 to 5 in the
      experiments and molecular dynamics simulations, respectively. An abrupt weakening
      is observed at a small D/d, while the strengths of large nanopillars are similar
      to bulk. This "smaller is weaker" trend is opposite to the "smaller is stronger"
      size effect in single crystalline nanostructures. The simulations demonstrate
      that the size-dependent behavior is associated with the distinct deformation
      mechanisms operative in interior versus surface grains.

PMID- 23148765
TI  - Respiratory proteins contribute differentially to Campylobacter jejuni's survival
      and in vitro interaction with hosts' intestinal cells.
AB  - BACKGROUND: The genetic features that facilitate Campylobacter jejuni's
      adaptation to a wide range of environments are not completely defined. However,
      whole genome expression studies showed that respiratory proteins (RPs) were
      differentially expressed under varying conditions and stresses, suggesting
      further unidentified roles for RPs in C. jejuni's adaptation. Therefore, our
      objectives were to characterize the contributions of selected RPs to C. jejuni's
      i- key survival phenotypes under different temperature (37 degrees C vs. 42
      degrees C) and oxygen (microaerobic, ambient, and oxygen-limited/anaerobic)
      conditions and ii- its interactions with intestinal epithelial cells from
      disparate hosts (human vs. chickens). RESULTS: C. jejuni mutant strains with
      individual deletions that targeted five RPs; nitrate reductase (DeltanapA),
      nitrite reductase (DeltanrfA), formate dehydrogenase (DeltafdhA), hydrogenase
      (DeltahydB), and methylmenaquinol:fumarate reductase (DeltamfrA) were used in
      this study. We show that only the DeltafdhA exhibited a decrease in motility;
      however, incubation at 42 degrees C significantly reduced the deficiency in the
      DeltafdhA's motility as compared to 37 degrees C. Under all tested conditions,
      the DeltamfrA showed a decreased susceptibility to hydrogen peroxide (H(2)O(2)),
      while the DeltanapA and the DeltafdhA showed significantly increased
      susceptibility to the oxidant as compared to the wildtype. Further, the
      susceptibility of the DeltanapA to H(2)O(2) was significantly more pronounced at
      37 degrees C. The biofilm formation capability of individual RP mutants varied as
      compared to the wildtype. However, the impact of the deletion of certain RPs
      affected biofilm formation in a manner that was dependent on temperature and/or
      oxygen concentration. For example, the DeltamfrA displayed significantly
      deficient and increased biofilm formation under microaerobic conditions at 37
      degrees C and 42 degrees C, respectively. However, under anaerobic conditions,
      the DeltamfrA was only significantly impaired in biofilm formation at 42 degrees
      C. Additionally, the RPs mutants showed differential ability for infecting and
      surviving in human intestinal cell lines (INT-407) and primary chicken intestinal
      epithelial cells, respectively. Notably, the DeltafdhA and the DeltahydB were
      deficient in interacting with both cell types, while the DeltamfrA displayed
      impairments only in adherence to and invasion of INT-407. Scanning electron
      microscopy showed that the DeltahydB and the DeltafdhA exhibited filamentous and
      bulging (almost spherical) cell shapes, respectively, which might be indicative
      of defects in cell division. CONCLUSIONS: We conclude that the RPs contribute to
      C. jejuni's motility, H(2)O(2) resistance, biofilm formation, and in vitro
      interactions with hosts' intestinal cells. Further, the impact of certain RPs
      varied in response to incubation temperature and/or oxygen concentration.
      Therefore, RPs may facilitate the prevalence of C. jejuni in a variety of niches,
      contributing to the pathogen's remarkable potential for adaptation.

PMID- 23148766
TI  - Intraoperative portable ultrasonography localization of clinically impalpable
      soft-tissue tumors.
AB  - BACKGROUND: Most soft-tissue tumors are clinically palpable; however, some can be
      impalpable to clinical examination making it difficult to plan surgical
      management. METHODS: We present a simple method of perioperative tumor
      localization using a portable ultrasonography machine. RESULTS: We used the
      technique for seven cases, on each occasion identifying the tumor and
      facilitating the optimal surgical approach. CONCLUSION: The technique is
      reproducible and readily available, and we recommend its use.

PMID- 23148767
TI  - Monophasic versus biphasic defibrillation for pediatric out-of-hospital cardiac
      arrest patients: a nationwide population-based study in Japan.
AB  - INTRODUCTION: Conventional monophasic defibrillators for out-of-hospital cardiac
      arrest patients have been replaced with biphasic defibrillators. However, the
      advantage of biphasic over monophasic defibrillation for pediatric out-of
      hospital cardiac-arrest patients remains unknown. This study aimed to compare the
      survival outcomes of pediatric out-of-hospital cardiac-arrest patients who
      underwent monophasic defibrillation with those who underwent biphasic
      defibrillation. METHODS: This prospective, nationwide, population-based
      observational study included pediatric out-of-hospital cardiac-arrest patients
      from January 1, 2005, to December 31, 2009. The primary outcome measure was
      survival at 1 month with minimal neurologic impairment. The secondary outcome
      measures were survival at 1 month and the return of spontaneous circulation
      before hospital arrival. Multivariable logistic regression analysis was performed
      to identify the independent association between defibrillator type (monophasic or
      biphasic) and outcomes. RESULTS: Among 5,628 pediatric out-of-hospital cardiac
      arrest patients (1 through 17 years old), 430 who received defibrillation shock
      with monophasic or biphasic defibrillator were analyzed. The number of patients
      who received defibrillation shock with monophasic defibrillator was 127 (30%),
      and 303 (70%) received defibrillation shock with biphasic defibrillator. The
      survival rates at 1 month with minimal neurologic impairment were 17.5% and
      24.4%, the survival rates at 1 month were 32.3% and 35.6%, and the rates of
      return of spontaneous circulation before hospital arrival were 24.4% and 27.4% in
      the monophasic and biphasic defibrillator groups, respectively. Hierarchic
      logistic regression analyses by using generalized estimation equations found no
      significant difference between the two groups in terms of 1-month survival with
      minimal neurologic impairment (odds ratio (OR), 1.57; 95% confidence interval
      (CI), 0.87 to 2.83; P = 0.14) and 1-month survival (OR, 1.38; 95% CI, 0.87 to
      2.18; P = 0.17). CONCLUSIONS: The present nationwide population-based
      observational study could not confirm an advantage of biphasic over monophasic
      defibrillators for pediatric OHCA patients.

PMID- 23148768
TI  - Prevalence and nature of criminal offending in a national sample of veterans in
      VA substance use treatment prior to the Operation Enduring Freedom/Operation
      Iraqi Freedom conflicts.
AB  - This study evaluated the prevalence and types of criminal arrest among 99,512
      male veterans in substance use disorder (SUD) treatment across 150 VA facilities
      from 1998 to 2001. Participants were assessed with the Addiction Severity Index
      (ASI), which includes detailed information about lifetime criminal activity. A
      majority of the patients (58.2%) had three or more previous arrests, with 46.0%
      reporting one or more criminal convictions. Criminal arrests were frequent and
      varied. A majority of patients (69.3%) had at least one arrest that was not due
      to drug possession, drug sale, or intoxication. Nearly 24% reported at least one
      arrest for a violent crime. Patterns of arrest for specific crimes varied across
      SUD diagnostic categories. Screening for specific types of offending is
      informative and viable. Existing VA SUD treatment is a potentially
      underrecognized point of intervention for justice involvement among veterans.

PMID- 23148769
TI  - Health service utilization before and after evidence-based treatment for PTSD.
AB  - Posttraumatic stress disorder (PTSD) is associated with functional impairment, co
      occurring diagnoses, and increased health care utilization. Associated high
      demand for health care services is an important contributor to the large public
      health cost of PTSD. Treatments incorporating exposure therapy are efficacious in
      ameliorating or eliminating PTSD symptoms. Accordingly, the Veterans Health
      Administration has made significant investments toward nationwide dissemination
      of a manualized exposure therapy protocol, prolonged exposure (PE). PE is
      effective with veterans; however, the relationship between PE and mental health
      service utilization is unknown. The current study investigates PE as it relates
      to actual tracked mental health service utilization in an urban VA medical
      center. A sample of 60 veterans with a diagnosis of PTSD was used to examine
      mental health service utilization in the 12-months prior to and 12-months after
      being offered PE. Hierarchical Linear Models and traditional repeated-measures
      ANOVA were used to estimate R2- and d-type effect sizes for service utilization.
      Associated estimated cost saving are reported. PE was associated with large
      reductions in symptoms and diagnosis remission. Treatment was also associated
      with statistically significant, large reductions in mental health service
      utilization for veterans who completed treatment. Findings suggest that expanding
      access to PE can increase access to mental health services in general by
      decreasing ongoing demand for specialty care clinical services.

PMID- 23148770
TI  - Effects of eliminating psychiatric rehabilitation from the secure levels of a
      mental-health service system.
AB  - Psychiatric rehabilitation (PR) is widely recognized as a treatment approach and
      an array of evidence-based practices effective for promoting the recovery of
      people with serious mental illness (SMI). However, its use in institutional
      settings is not widespread for unclear reasons. Policymakers may sometimes
      believe the superiority of PR in controlled research does not apply in the real
      world, for various reasons. This study exploits an unusual set of real-world
      circumstances surrounding the closure of a well-developed PR program in a state
      hospital. The program was closed after a period of mental-health services reform
      that significantly augmented the surrounding community-service system. The PR
      program was converted to conventional medical-institutional model-treatment units
      with no reduction in beds or funding within the state hospital. A database
      composed of public documents was used to analyze the consequences of the closing.
      Within the institution, the consequences included a persistent presence of long
      term difficult-to-discharge patients, a slowed discharge rate, a net increase in
      the hospital's per capita treatment costs, and higher use of restraint/seclusion.
      Effects were also detectable in the surrounding mental-health service system,
      including degraded outcome of community-based step-down services and increased
      pressure on emergency/crisis services. The consequences of closing the program
      are consistent with expectations based on research, and demonstrate danger in
      assuming that real world exigencies obviate research findings.

PMID- 23148771
TI  - The federal Post Conviction Risk Assessment (PCRA): a construction and validation
      study.
AB  - Offender assessment has been and remains the cornerstone of effective community
      supervision. This article presents the development of and tests the predictive
      validity of a 4th-generation risk assessment instrument designed for U.S.
      probation. A large administrative data set was used to create the assessment
      instrument and conduct an initial validation. Subsequent data generated from
      officer-completed assessments were used to conduct a prospective validation.
      Finally, data from case vignettes scored by trained officers were used to test
      the interrater agreement of the assessment instrument. Overall, analysis revealed
      that the assessment instrument predicted rearrest reliably when using the
      assessment results based on administrative data or officer-completed assessments.
      Analysis also revealed high rates of interrater agreement. Recommendations for
      future research and policy implications are presented.

PMID- 23148772
TI  - Considerations for planning and evaluating economic analyses of telemental
      health.
AB  - The economic evaluation of telemental health (TMH) is necessary to inform ways to
      decrease the cost of delivering care, to improve access to care, and to make
      decisions about the allocation of resources. Previous reviews of telehealth
      economic analysis studies have concluded that there are significant
      methodological deficiencies and inconsistencies that limit the ability to make
      generalized conclusions about the costs and benefits of telehealth programs.
      Published economic evaluations specific to TMH are also limited. There are unique
      factors that influence costs in TMH that are necessary for those who are planning
      and evaluating economic analyses to consider. The purpose of this review is to
      summarize the main problems and limitations of published economic analyses, to
      discuss considerations specific to TMH, and to inform and encourage the economic
      evaluation of TMH in both the public and private sectors. The topics presented
      here include perspective of costs, direct and indirect costs, and technology, as
      well as research methodology considerations. The integration of economic analyses
      into effectiveness trials, the standardization of outcome measurement, and the
      development of TMH economic evaluation guidelines are recommended.

PMID- 23148773
TI  - Computational design of effective, bioinspired HOCl antioxidants: the role of
      intramolecular Cl+ and H+ shifts.
AB  - The enzyme myeloperoxidase generates significant amounts of hypochlorous acid
      (HOCl) at sites of inflammation to inflict oxidative damage upon invading
      pathogens. However, excessive production of this potent oxidant is associated
      with numerous inflammatory diseases. Recent kinetic measurements suggest that the
      endogenous antioxidant carnosine is an effective HOCl scavenger. On the basis of
      computational modeling, we suggest a possible mechanism for this antioxidant
      activity. We find that a unique structural relationship between three adjacent
      functional groups (imidazole, carboxylic acid, and terminal amine) enables an
      intramolecular chlorine transfer to occur. In particular, two sequential proton
      shifts are coupled with a Cl(+) shift converting the kinetically favored product
      (chlorinated at the imidazole nitrogen) into the thermodynamically favored
      product (chlorinated at the terminal amine) effectively trapping the chlorine. We
      proceed to design systems that share similar structural features to those of
      carnosine but with even greater HOCl-scavenging capabilities.

PMID- 23148774
TI  - Frequency and burden of headache-related nausea: results from the American
      Migraine Prevalence and Prevention (AMPP) study.
AB  - BACKGROUND: While nausea is a defining feature of migraine, the association of
      nausea with other headache features and its influence on the burden of migraine
      have not been quantified. Population-based data were used to elucidate the
      relative frequency and burden of migraine-associated nausea in persons with
      migraine. METHODS: Participants with episodic migraine who completed the 2009
      American Migraine Prevalence and Prevention survey rated their headache-related
      nausea as occurring none of the time, rarely, <half the time, or >=half the time
      with their headaches. They also completed headache symptom severity and
      occupation/work status questions, the Headache Impact Test-6, and treatment
      attitude items that were part of the 2009 survey. Regression models that adjusted
      for both sociodemographic characteristics and symptom severity were used to
      assess the influence of nausea frequency on outcome measures. Partial and
      semipartial correlational analyses were used to estimate the influence of nausea
      alone and in combination with other headache symptoms on headache-related impact.
      RESULTS: Among the 6488 respondents with episodic migraine, approximately half
      (49.5%) reported high-frequency nausea (ie, >=half the time) with headache. High
      frequency nausea was more common in females than males (adjusted odds ratio 1.35,
      95% confidence interval 1.26-1.44). Persons with high-frequency nausea, compared
      with the no/rare or less than half the time nausea groups, reported significantly
      more headache symptoms and more headache-related impact as measured by the
      Headache Impact Test-6. High-frequency nausea was also associated with being
      occupationally disabled or on medical leave, and more self-reported financial
      burden of headache medications, worry about running out of headache
      medication(s), and that headache medications interfered with work or school work,
      household work, and family/leisure activities. Regression-based correlational
      analyses indicated that nausea contributes significantly and independently to
      headache-related impact. CONCLUSIONS: High-frequency migraine-associated nausea
      is common and is a marker for severe, debilitating migraine. Nausea makes an
      independent contribution to migraine-associated disability and impact. Management
      strategies that take nausea into account could reduce the burden of migraine.
      Nausea is an important target for monitoring and treatment.

PMID- 23148775
TI  - Spontaneous combined rupture of a pelvicalyceal cyst into the collector system
      and retroperitoneal space during the acquisition of computed tomography scan
      images: a case report.
AB  - INTRODUCTION: Pelvicalyceal cysts are common findings in autopsies and can
      manifest with a variety of patterns. These cystic lesions are usually a benign
      entity with no clinical significance unless they enlarge enough to cause
      compression of the adjacent collecting system and consequently obstructive
      uropathy. Few cases of the spontaneous rupture of pelvicalyceal renal cysts have
      been published and to the best of our knowledge there is no report of a combined
      rupture to collector system and retroperitoneal space documented during a
      multiphase computed tomography. CASE PRESENTATION: We report a case of a 'real
      time' spontaneous rupture of a pelvicalyceal cyst into the collecting system with
      fistulization into the retroperitoneum.The patient was a 78-year-old Caucasian
      man with a previous history of renal stones and a large pelvicalyceal renal cyst
      who was admitted to our Emergency department with acute right flank pain.A
      multiphase computed tomography was performed and the pre-contrast images
      demonstrated a right pelvicalyceal renal cyst measuring 12.0 * 6.1cm in the lower
      pole causing moderate dilation of the upper right renal collection system. In
      addition, a partially obstructive stone on the left distal ureter with mild left
      hydronephrosis was noted.The nephrographic phase did not add any new information.
      The excretory phase (10-minute delay) demonstrated a spontaneous rupture of the
      cyst into the pelvicalyceal system with posterior fistulization into the
      retroperitoneal space. CONCLUSION: In this case study we present time-related
      changes of a rare pelvicalyceal cyst complication, which to the best of our
      knowledge has fortunately not been previously documented. Analysis of the
      sequential images and comparison with an earlier scan allowed us to better
      understand the physiopathological process of the rupture, the clinical
      presentation and to elaborate hypotheses for its etiopathogenesis.

PMID- 23148776
TI  - Structural basis for progression toward the carbapenemase activity in the GES
      family of beta-lactamases.
AB  - Carbapenem antibiotics have become therapeutics of last resort for the treatment
      of difficult infections. The emergence of class-A beta-lactamases that have the
      ability to inactivate carbapenems in the past few years is a disconcerting
      clinical development in light of the diminished options for treatment of
      infections. A member of the GES-type beta-lactamase family, GES-1, turns over
      imipenem poorly, but the GES-5 beta-lactamase is an avid catalyst for turnover of
      this antibiotic. We report herein high-resolution X-ray structures of the apo GES
      5 beta-lactamase and the GES-1 and GES-5 beta-lactamases in complex with
      imipenem. The latter are the first structures of native class-A carbapenemases
      with a clinically used carbapenem antibiotic in the active site. The structural
      information is supplemented by information from molecular dynamics simulations,
      which collectively for the first time discloses how the second step of catalysis
      by these enzymes, namely, hydrolytic deacylation of the acyl-enzyme species,
      takes place effectively in the case of the GES-5 beta-lactamase and significantly
      less so in GES-1. This information illuminates one evolutionary path that nature
      has taken in the direction of the inexorable emergence of resistance to
      carbapenem antibiotics.

PMID- 23148777
TI  - Study of pH-induced folding and unfolding kinetics of the DNA i-motif by stopped
      flow circular dichroism.
AB  - Using the stopped-flow circular dichroism (SFCD) technique, we investigate the
      kinetics of the pH-induced folding and unfolding process of the DNA i-motif. The
      results show that the molecule can fold or unfold on a time scale of 100 ms when
      the solution pH is changed. It is also found that the folding and unfolding rates
      strongly depend on the solution pH. On the basis of quantitative data, we propose
      theoretical models to decipher the folding and unfolding kinetics. Our models
      suggest that the cooperativity of protons is crucial for both the folding and
      unfolding process. In the unfolding process, the cooperative neutralization of
      two protons (out of the total six protons in the i-motif molecule) is the only
      rate-limiting step. In the folding process, there exists a critical step in which
      three protons bind cooperatively to the DNA strand. These results offer an in
      depth understanding of the folding and unfolding kinetics of the DNA i-motif and
      may give precise guidance for constructing novel nanodevices based on the DNA i
      motif.

PMID- 23148778
TI  - HGF stimulation of Rac1 signaling enhances pharmacological correction of the most
      prevalent cystic fibrosis mutant F508del-CFTR.
AB  - Cystic fibrosis (CF), a major life-limiting genetic disease leading to severe
      respiratory symptoms, is caused by mutations in CF transmembrane conductance
      regulator (CFTR), a chloride (Cl(-)) channel expressed at the apical membrane of
      epithelial cells. Absence of functional CFTR from the surface of respiratory
      cells reduces mucociliary clearance, promoting airways obstruction, chronic
      infection, and ultimately lung failure. The most frequent mutation, F508del,
      causes the channel to misfold, triggering its premature degradation and
      preventing it from reaching the cell surface. Recently, novel small-molecule
      correctors rescuing plasma membrane localization of F508del-CFTR underwent
      clinical trials but with limited success. Plausibly, this may be due to the
      mutant intrinsic plasma membrane (PM) instability. Herein, we show that
      restoration of F508del-CFTR PM localization by correctors can be dramatically
      improved through a novel pathway involving stimulation of signaling by the
      endogenous small GTPase Rac1 via hepatocyte growth factor (HGF). We first show
      that CFTR anchors to apical actin cytoskeleton (via Ezrin) upon activation of
      Rac1 signaling through PIP5K and Arp2/3. We then found that such anchoring
      retains pharmacologically rescued F508del-CFTR at the cell surface, boosting
      functional restoration by correctors up to 30% of wild-type channel levels in
      human airway epithelial cells. Our findings reveal that surface anchoring and
      retention is a major target pathway for CF pharmacotherapy, namely, to achieve
      maximal restoration of F508del-CFTR in patients in combination with correctors.
      Moreover, this approach may also translate to other disorders caused by
      trafficking-deficient surface proteins.

PMID- 23148779
TI  - Stability of implants placed in augmented posterior mandible after alveolar
      osteotomy using resorbable nonceramic hydroxyapatite or intraoral autogenous
      bone: 12-month follow-up.
AB  - PURPOSE: This prospective, controlled split-mouth study evaluated the stability
      of dental implants placed in the augmented mandibular areas with alveolar
      segmental "sandwich" osteotomies using nonceramic hydroxyapatite (ncHA) or
      autogenous bone. MATERIAL AND METHODS: This study included 11 bilaterally
      partially edentulous mandibular patients in a split-mouth design. Alveolar
      augmentation osteotomies were performed bilaterally with interpositional ncHA
      graft (test group) or interpositional intraoral autogenous bone graft (control
      group). After 6 months of healing, four implants (two implants in each side) were
      placed in each patient. Forty-four implants were inserted and loaded after 6
      month healing period. At 1-year follow-up, radiographic, prosthetic, and
      resonance frequency analysis parameters were assessed. Success criteria included
      absence of pain, sensitivity, suppuration, and implant mobility; absence of
      continuous peri-implant radiolucency; and distance between the implant shoulder
      and the first visible bone contact (DIB) < 2 mm. RESULTS: After a 1-year loading
      period, the overall implant survival rate was 95.45%, with two implant losses
      (one of each group). Among the surviving implants (42 out of 44), two did not
      fulfill the success criteria; therefore, the implant success was 90.90%. DIB was
      0.71 +/- 0.70 and 0.84 +/- 0.72 mm for ncHA and autogenous bone grafts,
      respectively (p > .05). Implant stability measurements were similar between the
      groups during the 12-month follow-up (p > .05). CONCLUSION: Within the limits of
      this study, the implants placed either in sites augmented with ncHA or autogenous
      bone seem to represent a safe and successful procedure, at least, after 12-month
      follow-up.

PMID- 23148780
TI  - The role of platelet activation in determining response to therapy in patients
      with primary nephrotic syndrome.
AB  - To test the role of platelet activation in the prognosis of nephrotic syndrome
      (NS), we evaluated the mean platelet volume (MPV) in patients with NS undergoing
      treatment. In this prospective, multicenter clinical study 156 patients with
      primary NS under treatment were assigned and followed for one year. Patients were
      divided into three groups for complete remission, partial remission, and
      resistance. Biochemical parameters, estimated glomerular filtration rate,
      proteinuria level, and MPV levels were compared at baseline and 12 months after
      treatment. MPV, proteinuria, total cholesterol, triglyceride, LDL cholesterol,
      HDL cholesterol, total protein, albumin, and hs-CRP levels significantly
      decreased in partial and complete remission group after 12 months compared to the
      baseline (p < 0.05). However, MPV levels significantly increased and only LDL
      cholesterol significantly decreased in the resistance group (p < 0.05).
      Univariate analyses demonstrated that DeltaMPV was significantly associated with
      Deltaproteinuria (r = 0.41, p < 0.001), Deltahs-CRP (r = 0.39, p < 0.001), and
      DeltaAlbumin (r = -0.30, p < 0.001). We found that DeltaAlbumin (beta = -0.33, p
      < 0.001), DeltaTotal cholesterol (beta = -0.20, p = 0.011), and Deltahs-CRP (beta
      = 0.19, p = 0.018) were statistically significant predictors of the
      Deltaproteinuria in multiple regression analysis. In subjects with primary NS,
      MPV is associated with the prognosis or the disease. This study provides the
      background for longer trials and the role of platelet activation in NS. 

PMID- 23148782
TI  - Heightened attentional capture by threat in veterans with PTSD.
AB  - Although an attentional bias for threat-relevant cues has been theorized in
      posttraumatic stress disorder (PTSD), to date empirical demonstration of this
      phenomenon has been at best inconsistent. Furthermore, the nature of this bias in
      PTSD has not been clearly delineated. In the present study, veterans with PTSD (n
      = 20), trauma-exposed veterans without PTSD (n = 16), and healthy nonveteran
      controls (n = 22) completed an emotional attentional blink task that measures the
      extent to which emotional stimuli capture and hold attention. Participants
      searched for a target embedded within a series of rapidly presented images.
      Critically, a combat-related, disgust, positive, or neutral distracter image
      appeared 200 ms, 400 ms, 600 ms, or 800 ms before the target. Impaired target
      detection was observed among veterans with PTSD relative to both veterans without
      PTSD and healthy nonveteran controls after only combat-related threat distracters
      when presented 200 ms, 400 ms, or 600 ms before the target, indicating increased
      attentional capture by cues of war and difficulty disengaging from such cues for
      an extended period. Veterans without PTSD and healthy nonveteran controls did not
      significantly differ from each other in target detection accuracy after combat
      related threat distracters. These data support the presence of an attentional
      bias toward combat related stimuli in PTSD that should be a focus of treatment
      efforts.

PMID- 23148783
TI  - A psychophysiological investigation of threat and reward sensitivity in
      individuals with panic disorder and/or major depressive disorder.
AB  - Heightened sensitivity to threat and reduced sensitivity to reward are potential
      mechanisms of dysfunction in anxiety and depressive disorders, respectively.
      However, few studies have simultaneously examined whether these mechanisms are
      unique or common to these disorders. In this study, sensitivity to predictable
      and unpredictable threat (measured by startle response during threat
      anticipation) and sensitivity to reward (measured by frontal
      electroencephalographic [EEG] asymmetry during reward anticipation) were assessed
      in 4 groups (N = 191): those with (1) panic disorder (PD) without a lifetime
      history of depression, (2) major depression (MDD) without a lifetime history of
      an anxiety disorder, (3) comorbid PD and MDD, and (4) controls. General
      distress/negative temperament (NT) was also assessed via self-report. Results
      indicated that PD (with or without comorbid MDD) was uniquely associated with
      heightened startle to predictable and unpredictable threat, and MDD (with or
      without comorbid PD) was uniquely associated with reduced frontal EEG asymmetry.
      Both psychophysiological measures of threat and reward sensitivity were stable on
      retest approximately 9 days later in a subsample of participants. Whereas the
      comorbid group did not respond differently on the tasks relative to the PD-only
      and MDD-only groups, they did report greater NT than these 2 groups (which did
      not differ from each other). Results suggest that heightened sensitivity to
      threat and reduced sensitivity to reward may be specific components of PD and
      MDD, respectively. In addition, relative to noncomorbid depression and PD,
      comorbid MDD and PD may be characterized by heightened NT, but not abnormal
      levels of these "specific" components.

PMID- 23148785
TI  - Computed tomography scan in supine and prone positions: an alternative method to
      detect intramural gas in emphysematous cystitis and to evaluate efficacy after
      adjuvant continuous intravesical irrigation treatment.
AB  - OBJECTIVE: To evaluate the efficacy of continuous intravesical irrigation with
      saline plus amikacin as adjuvant therapy and to evaluate the computed tomography
      (CT) scan in supine and prone positions (CystoCT scan) as an alternative
      diagnostic and evaluation method of intramural gas in emphysematous cystitis (EC)
      before and after treatment. METHODS: Consecutive patients with a diagnosis of EC
      who were hospitalized between March 2006 and January 2011 were investigated. The
      diagnosis was made by CystoCT scan. Treatment consisted of intravenous
      antibiotics, control of concomitant diseases, and placement of a 3-way urinary
      catheter for continuous irrigation of 500 mg of amikacin diluted in 1 l of saline
      given on days 0, 3, and 7. Treatment was considered successful when there was an
      absence of gas in the bladder wall, the urine culture was negative, there was
      clinical improvement, and there was an absence of toxicity. RESULTS: Eleven
      patients were hospitalized with a diagnosis of EC during the study period. Four
      were excluded from the study, 2 due to the lack of confirmation of the diagnosis
      with the CystoCT scan. Treatment was successful in all patients; for 6 (86%) this
      was achieved in 3 days and for 1 (14%) in 7 days. No toxicity was reported.
      CONCLUSIONS: Continuous intravesical irrigation with saline plus amikacin as
      adjuvant treatment of EC is an inexpensive, effective, and safe tool that might
      help conventional treatment and provide a rapid recovery. The CystoCT scan is an
      alternative method to diagnose and evaluate intramural gas in EC patients. These
      findings should be challenged in a randomized, multi-centre, placebo-controlled
      clinical trial.

PMID- 23148784
TI  - Prevalence, incidence, impairment, and course of the proposed DSM-5 eating
      disorder diagnoses in an 8-year prospective community study of young women.
AB  - We examined prevalence, incidence, impairment, duration, and course for the
      proposed DSM-5 eating disorders in a community sample of 496 adolescent females
      who completed annual diagnostic interviews over 8 years. Lifetime prevalence by
      age 20 was 0.8% for anorexia nervosa (AN), 2.6% for bulimia nervosa (BN), 3.0%
      for binge eating disorder (BED), 2.8% for atypical AN, 4.4% for subthreshold BN,
      3.6% for subthreshold BED, 3.4% for purging disorder (PD), and combined
      prevalence of 13.1% (5.2% had AN, BN, or BED; 11.5% had feeding and eating
      disorders not elsewhere classified; FED-NEC). Peak onset age was 19-20 for AN, 16
      20 for BN, and 18-20 for BED, PD, and FED-NEC. Youth with these eating disorders
      typically reported greater functional impairment, distress, suicidality, mental
      health treatment, and unhealthy body mass index, though effect sizes were
      relatively smaller for atypical AN, subthreshold BN, and PD. Average episode
      duration in months ranged from 2.9 for BN to 11.2 for atypical AN. One-year
      remission rates ranged from 71% for atypical AN to 100% for BN, subthreshold BN,
      and BED. Recurrence rates ranged from 6% for PD to 33% for BED and subthrehold
      BED. Diagnostic progression from subthreshold to threshold eating disorders was
      higher for BN and BED (32% and 28%) than for AN (0%), suggesting some sort of
      escalation mechanism for binge eating. Diagnostic crossover was greatest from BED
      to BN. Results imply that the new DSM-5 eating disorder criteria capture
      clinically significant psychopathology and usefully assign eating disordered
      individuals to homogeneous diagnostic categories.

PMID- 23148786
TI  - Cross-reactions of sera from dogs infected with Angiostrongylus vasorum in
      commercially available Dirofilaria immitis test kits.
AB  - BACKGROUND: Dirofilaria immitis and Angiostrongylus vasorum are both important
      potentially fatal canine nematodes with overlapping endemic areas, especially in
      Europe. The preadult and adult stages of both species are living in the Arteria
      pulmonalis and the right heart, and diagnostically detectable circulating
      parasite antigens have been demonstrated for both species. For the detection of
      D. immitis infections, a variety of commercial tests have been developed,
      however, they have not been evaluated for cross-reactions against circulating
      antigens of A. vasorum. METHODS: In this study, potential cross-reactions of sera
      from 16 dogs, which were experimentally infected with A. vasorum and which had
      circulating antigens as confirmed by a species-specific ELISA, were evaluated for
      the detection of A. vasorum antigen in six commercially available D. immitis test
      kits. RESULTS: In three fast tests (Witness(r) Dirofilaria, SensPERT(r) Canine
      Heartworm, SNAP(r) 4Dx(r) Plus), all sera were negative. One fast membrane ELISA
      (SNAP(r) HTWM RT Test) was positive with four sera (25%), and one serum delivered
      a non-valid result twice. In the PetChek(r) HTWM PF Test, depending on the
      interpretation protocol, 5 or 8 dogs (31.2 - 50%) were positive. With the
      DiroCHEK(r)-ELISA, a single A. vasorum-infected dog (6.2%) tested positive.
      CONCLUSIONS: Due to potential cross-reactions with A. vasorum in commercially
      available test kits for the detection of D. immitis antigen, the simultaneous use
      of highly specific diagnostic methods for the differentiation of these two canine
      heart worms is recommended.

PMID- 23148787
TI  - Optimal vaccination schedule search using genetic algorithm over MPI technology.
AB  - BACKGROUND: Immunological strategies that achieve the prevention of tumor growth
      are based on the presumption that the immune system, if triggered before tumor
      onset, could be able to defend from specific cancers. In supporting this
      assertion, in the last decade active immunization approaches prevented some virus
      related cancers in humans. An immunopreventive cell vaccine for the non-virus
      related human breast cancer has been recently developed. This vaccine, called
      Triplex, targets the HER-2-neu oncogene in HER-2/neu transgenic mice and has
      shown to almost completely prevent HER-2/neu-driven mammary carcinogenesis when
      administered with an intensive and life-long schedule. METHODS: To better
      understand the preventive efficacy of the Triplex vaccine in reduced schedules we
      employed a computational approach. The computer model developed allowed us to
      test in silico specific vaccination schedules in the quest for optimality.
      Specifically here we present a parallel genetic algorithm able to suggest optimal
      vaccination schedule. RESULTS & CONCLUSIONS: The enormous complexity of
      combinatorial space to be explored makes this approach the only possible one. The
      suggested schedule was then tested in vivo, giving good results. Finally,
      biologically relevant outcomes of optimization are presented.

PMID- 23148788
TI  - Conceptualising global health: theoretical issues and their relevance for
      teaching.
AB  - BACKGROUND: There has long been debate around the definition of the field of
      education, research and practice known as global health. In this article we step
      back from attempts at definition and instead ask what current definitions tell us
      about the evolution of the field, identifying gaps and points of debate and using
      these to inform discussions of how global health might be taught. DISCUSSION:
      What we now know as global health has its roots in the late 19(th) century, in
      the largely colonial, biomedical pursuit of 'international health'. The twentieth
      century saw a change in emphasis of the field towards a much broader
      conceptualisation of global health, encompassing broader social determinants of
      health and a truly global focus. The disciplinary focus has broadened greatly to
      include economics, anthropology and political science, among others. There have
      been a number of attempts to define the new field of global health. We suggest
      there are three central areas of contention: what the object of knowledge of
      global health is, the types of knowledge to be used and around the purpose of
      knowledge in the field of global health. We draw a number of conclusions from
      this discussion. First, that definitions should pay attention to differences as
      well as commonalities in different parts of the world, and that the definitions
      of global health themselves depend to some extent on the position of the definer.
      Second, global health's core strength lies in its interdisciplinary character, in
      particular the incorporation of approaches from outside biomedicine. This
      approach recognises that political, social and economic factors are central
      causes of ill health. Last, we argue that definition should avoid inclusion of
      values. In particular we argue that equity, a key element of many definitions of
      global health, is a value-laden concept and carries with it significant
      ideological baggage. As such, its widespread inclusion in the definitions of
      global health is inappropriate as it suggests that only people sharing these
      values may be seen as 'doing' global health. Nevertheless, discussion of values
      should be a key part of global health education. SUMMARY: Our discussions lead us
      to emphasise the importance of an approach to teaching global health that is
      flexible, interdisciplinary and acknowledges the different interpretations and
      values of those practising and teaching the field.

PMID- 23148791
TI  - Prevalence and correlates of sexual behaviors among university students: a study
      in Hefei, China.
AB  - BACKGROUND: In China, sexual health and behaviors of young people have become a
      growing public concern but few studies have been conducted to investigate the
      prevalence and psychosocial correlates of the phenomenon. METHODS: A self
      reported questionnaire survey on youth sexual behaviors was conducted among 1,500
      university students in 2011 at Hefei, a middle-size city in eastern China. A
      total of 1,403 students (age = 20.30 +/- 1.27 years) completed the questionnaire
      with a high response rate of 93.5%. RESULTS: Among the respondents, 12.6% (15.4%
      of male versus 8.6% of female) students reported having pre-marital heterosexual
      intercourse; 10.8% (10.5% of males versus 11.2% females) had oral sex; 2.7% (3.4%
      of males versus 1.7% females) reported same-sex activities; 46% (70.3% of males
      versus 10.8% of females) reported masturbation behaviors; 57.4% (86.2% of males
      versus 15.6% females) students viewed pornography. In terms of sexual
      communication about sexual knowledge acquisition, 13.7% (10.7% of males versus
      18% of females) talked to their parents about sex; 7.1% (6.1% of males versus
      8.4% of females) students reported having conversation with parents on
      contraception. About forcing sexual behavior, 2.7% (4% of males versus 0.9% of
      females) reported forcing their sexual partners to have sex, and 1.9% (2.4% of
      males versus 1.2% of females) reported being forced to have sex. Gender was found
      to be significant predictor of sexual behaviors in university students: males
      reported more sexual behaviors including sexual fantasy, heterosexual
      intercourse, masturbation, viewing pornography and talking about sex with
      friends. Several correlates of sexual behaviors were identified for students of
      different gender separately. For males, having romantic relationships, past sex
      education experiences, low educational aspirations, time spent on the Internet,
      and urban native settings were significantly associated with more sexual
      behaviors. For female students, having romantic relationships and urban native
      settings predicted sexual behaviors. CONCLUSION: Sexual behavior among University
      students in China is not uncommon, although there are limited ways for students
      to acquire sex-related knowledge: male students showed significantly more sexual
      behaviors than female students. Having romantic relationships and more time spent
      online were important predictors of sexual behaviors among university students.
      To guide healthy sexual behaviors in young people, comprehensive sex education
      programs that provide necessary sexual health knowledge about safe sex should be
      developed and implemented in universities in China, particularly for students who
      have romantic relationships and those who spend long periods of time on the
      Internet.

PMID- 23148792
TI  - Characteristics of primary care office visits to nurse practitioners, physician
      assistants and physicians in United States Veterans Health Administration
      facilities, 2005 to 2010:  a retrospective cross-sectional analysis.
AB  - BACKGROUND: Primary care, an essential determinant of health system equity,
      efficiency, and effectiveness, is threatened by inadequate supply and
      distribution of the provider workforce. The Veterans Health Administration (VHA)
      has been a frontrunner in the use of nurse practitioners (NPs) and physician
      assistants (PAs). Evaluation of the roles and impact of NPs and PAs in the VHA is
      critical to ensuring optimal care for veterans and may inform best practices for
      use of PAs and NPs in other settings around the world. The purpose of this study
      was to characterize the use of NPs and PAs in VHA primary care and to examine
      whether their patients and patient care activities were, on average, less
      medically complex than those of physicians. METHODS: This is a retrospective
      cross-sectional analysis of administrative data from VHA primary care encounters
      between 2005 and 2010. Patient and patient encounter characteristics were
      compared across provider types (PA, NP, and physician). RESULTS: NPs and PAs
      attend about 30% of all VHA primary care encounters. NPs, PAs, and physicians
      fill similar roles in VHA primary care, but patients of PAs and NPs are slightly
      less complex than those of physicians, and PAs attend a higher proportion of
      visits for the purpose of determining eligibility for benefits. CONCLUSIONS: This
      study demonstrates that a highly successful nationwide primary care system relies
      on NPs and PAs to provide over one quarter of primary care visits, and that these
      visits are similar to those of physicians with regard to patient and encounter
      characteristics. These findings can inform health workforce solutions to
      physician shortages in the USA and around the world. Future research should
      compare the quality and costs associated with various combinations of providers
      and allocations of patient care work, and should elucidate the approaches that
      maximize quality and efficiency.

PMID- 23148793
TI  - Eosinophilic panniculitis presenting with Kaposi's sarcoma-like plaques in a
      patient who is human immunodeficiency virus positive: a case report.
AB  - INTRODUCTION: Eosinophilic panniculitis is an unusual type of panniculitis
      characterized by a prominent infiltration of subcutaneous fat with eosinophils
      without an exact etiopathogenesis. To the best of our knowledge, up to now
      eosinophilic panniculitis has been described in only one previous case with human
      immunodeficiency virus disease in the literature. CASE PRESENTATION: Here we
      report the case of a 44-year-old Caucasian man, who is human immunodeficiency
      virus positive, diagnosed with eosinophilic panniculitis. A dermatological
      examination revealed multiple, confluent Kaposi's sarcoma-like purple colored,
      deep plaques and nodules on his right gluteal area and right thigh. The presence
      of the mixed inflammatory infiltrate of lymphocytes, macrophages, and numerous
      eosinophils involving both septa and lobules of the subcutis were noted on the
      histopathological examination. On the basis of all these clinical and
      histopathological findings the patient was diagnosed with eosinophilic
      panniculitis. He was given intravenous 60mg/day methylprednisolone for 3
      consecutive days a week for 6 months. The lesions resolved almost completely
      after 6 months. CONCLUSION: The predominance of T helper-2 subset of T helper
      cells and the consequential increase in interleukin-5 cytokines accompanying
      peripheral eosinophilia and high serum immunoglobulin E levels may all be blamed
      for the development of eosinophilic panniculitis in our case study. As a result,
      we aim to emphasize that eosinophilic panniculitis should be kept in mind in the
      differential diagnosis of subcutaneous nodular lesions in patients who are human
      immunodeficiency virus positive. We also focus on the requirement of
      histopathological examination for the definitive diagnosis because the clinical
      features of eosinophilic panniculitis may easily be confused with Kaposi's
      sarcoma.

PMID- 23148794
TI  - Near patient anti-platelet response testing over time and gene analysis in
      patients admitted with acute coronary syndromes.
AB  - We sought to assess the relationships between platelet reactivity at different
      time points, CYP2C19*2 and ABCB1 status and clinical outcomes in patients with
      acute coronary syndromes (ACS). Anti-platelet response to clopidogrel was studied
      prospectively using the VerifyNow (VN) P2Y12 assay at the time of angiography and
      at 30 days post procedure in 151 patients admitted with ACS who underwent
      percutaneous coronary intervention (PCI). Troponin T levels were measured at
      angiography and 16-24 hour following PCI. DNA was extracted and the presence of
      CYP2C19*2 allele and ABCB1 polymorphisms were determined. Adverse cardiovascular
      and cerebral events (ACCE) were assessed at 12 months. High VN P2Y12 response at
      angiography was associated with a greater peri-procedural rise in troponin T, but
      not ACCE. However, VN P2Y12 response measured at 30 days was associated with ACCE
      (p = 0.017). CYP2C19*2 status was associated with higher VN P2Y12 response at
      angiography (p < 0.0001) and 30 days (p = 0.006) but not ACCE. Near-patient
      testing for clopidogrel response was associated with subsequent ACCE when
      performed 30 days following PCI, but not at angiography. 

PMID- 23148795
TI  - A method for high throughput determination of viable bacteria cell counts in 96
      well plates.
AB  - BACKGROUND: There are several methods for quantitating bacterial cells, each with
      advantages and disadvantages. The most common method is bacterial plating, which
      has the advantage of allowing live cell assessment through colony forming unit
      (CFU) counts but is not well suited for high throughput screening (HTS). On the
      other hand, spectrophotometry is adaptable to HTS applications but does not
      differentiate between dead and living bacteria and has low sensitivity. RESULTS:
      Here, we report a bacterial cell counting method termed Start Growth Time (SGT)
      that allows rapid and serial quantification of the absolute or relative number of
      live cells in a bacterial culture in a high throughput manner. We combined the
      methodology of quantitative polymerase chain reaction (qPCR) calculations with a
      previously described qualitative method of bacterial growth determination to
      develop an improved quantitative method. We show that SGT detects only live
      bacteria and is sensitive enough to differentiate between 40 and 400 cells/mL.
      SGT is based on the re-growth time required by a growing cell culture to reach a
      threshold, and the notion that this time is proportional to the number of cells
      in the initial inoculum. We show several applications of SGT, including
      assessment of antibiotic effects on cell viability and determination of an
      antibiotic tolerant subpopulation fraction within a cell population. SGT results
      do not differ significantly from results obtained by CFU counts. CONCLUSION: SGT
      is a relatively quick, highly sensitive, reproducible and non-laborious method
      that can be used in HTS settings to longitudinally assess live cells in bacterial
      cell cultures.

PMID- 23148797
TI  - Intermolecular/interionic vibrations of 1-methyl-3-n-octylimidazolium
      tetrafluoroborate ionic liquid and H2O mixtures.
AB  - We report here the low-frequency spectra, resulting from the
      intermolecular/interionic vibrational dynamics, of aqueous mixtures of an ionic
      liquid, 1-methyl-3-n-octylimidazolium tetrafluoroborate, with the H(2)O mole
      fractions of 0.2, 0.4, and 0.6 and the neat ionic liquid and H(2)O within the
      frequency range of 0.1-700 cm(-1) by means of femtosecond Raman-induced Kerr
      effect spectroscopy. Addition of H(2)O induces tiny effects on the line shape of
      the low-frequency Kerr spectrum of the ionic liquid: ca. a 2 cm(-1) red shift in
      the first moment of the low-frequency spectrum has been observed for a transition
      from the neat ionic liquid to the binary mixture containing 0.6 mol fraction of
      H(2)O. Surface tension and liquid density of the mixture also accompany minimal
      changes upon addition of H(2)O. These results suggest that H(2)O molecules
      localize at the interface between the ionic and nonpolar regions, and the
      interionic interaction in the ionic region is weakly perturbed by the existence
      of H(2)O. On the other hand, successive addition of H(2)O in the mixture slows
      down the picosecond overdamped relaxation process measured in the 3-300 ps range
      even though the shear viscosity of the mixture decreases substantially.

PMID- 23148796
TI  - Aromatic-proline interactions: electronically tunable CH/pi interactions.
AB  - Proline residues have unique roles in protein folding, structure, and function.
      Proline and the aromatic amino acids comprise the encoded cyclic protein
      residues. Aromatic protein side chains are defined by their negatively charged pi
      faces, while the faces of the proline ring are partially positively charged. This
      polarity results from their two-point connection of the side chain to the
      electron-withdrawing protein backbone, and the lower electronegativity of
      hydrogen compared to carbon, nitrogen, and oxygen. The hydrogens adjacent to the
      carbonyl and amide nitrogen, Halpha and Hdelta, respectively, are the most
      partially positive. Proline's side chain is also conformationally restricted,
      allowing for interaction with aromatic residues with minimal entropic or steric
      penalty. Proline and aromatic residues can interact favorably with each other,
      due to both the hydrophobic effect and the interaction between the pi aromatic
      face and the polarized C-H bonds, called a CH/pi interaction. Aromatic-proline
      interactions can occur locally, for example, to stabilize cis-amide bonds, and
      over larger distances, in the tertiary structures of proteins, and
      intermolecularly in protein-protein interactions. In peptides and proteins,
      aromatic-proline sequences more readily adopt cis-prolyl amide bonds, where the
      aromatic ring interacts with the proline ring in the cis conformation. In
      aromatic-proline sequences, Trp and Tyr are more likely to induce cis-amide bonds
      than Phe, suggesting an aromatic electronic effect. This result would be expected
      for a CH/pi interaction, in which a more electron-rich aromatic would have a
      stronger (more cis-stabilizing) interaction with partial positive charges on
      prolyl hydrogens. In this Account, we describe our investigations into the nature
      of local aromatic-proline interactions, using peptide models. We synthesized a
      series of 26 peptides, TXPN, varying X from electron-rich to electron poor
      aromatic amino acids, and found that the population of cis-amide bond
      (Ktrans/cis) is tunable by aromatic electronics. With 4-substituted
      phenylalanines, we observed a Hammett correlation between aromatic electronics
      and Ktrans/cis, with cis-trans isomerism electronically controllable by 1.0
      kcal/mol. All aromatic residues exhibit a higher cis population than Ala or
      cyclohexylalanine, with Trp showing the strongest aromatic-proline interaction.
      In addition, proline stereoelectronic effects can modulate cis-trans isomerism by
      an additional 1.0 kcal/mol. The aromatic-proline interaction is enthalpic,
      consistent with its description as a CH/pi interaction. Proline-aromatic
      sequences can also promote cis-prolyl bonds, either through interactions of the
      aromatic ring with the preceding cis-proline or with the Halpha prior to cis
      proline. Within proline-rich peptides, sequences commonly found in natively
      disordered proteins, aromatic residues promote multiple cis-amide bonds due to
      multiple favorable aromatic-proline interactions. Collectively, we found aromatic
      proline interactions to be significantly CH/pi in nature, tunable by aromatic
      electronics. We discuss these data in the context of aromatic-proline and
      aromatic-glycine interactions in local structure, in tertiary structure, in
      protein-protein interactions, and in protein assemblies.

PMID- 23148798
TI  - Decisions during negatively-framed messages yield smaller risk-aversion-related
      brain activation in substance-dependent individuals.
AB  - A sizable segment of addiction research investigates the effects of persuasive
      message appeals on risky and deleterious behaviors. However, to date, little
      research has examined how various forms of message framing and corresponding
      behavioral choices might by mediated by risk-related brain regions. Using event
      related functional MRI, we investigated brain regions hypothesized to mediate the
      influence of message appeals on decision making in substance-dependent (SD)
      compared with nonsubstance-dependent (non-SD) individuals. The Iowa Gambling Task
      (IGT) was modified to include positively-framed, negatively-framed, and control
      messages about long-term deck payoffs. In the positively-framed condition, the SD
      and non-SD groups showed improved decision-making performance that corresponded
      to higher risk-aversion-related brain activity in the anterior cingulate cortex
      (ACC) and anterior insula (AI). In contrast, in the negatively-framed condition,
      the SD group showed poorer performance that corresponded to lower risk-aversion
      related brain activity in the AI region. In addition, only the non-SD group
      showed a positive association between decision quality and greater risk-related
      activity in the ACC, regardless of message type. The findings suggest substance
      dependent individuals may have reduced neurocognitive sensitivity in the ACC and
      AI regions involved in risk perception and aversion during decision-making,
      especially in response to framed messages that emphasize reduced prospects for
      long-term gains.

PMID- 23148799
TI  - An open-label trial of a sumatriptan auto-injector for migraine in patients
      currently treated with subcutaneous sumatriptan.
AB  - OBJECTIVE: To assess the ability of patients, during an acute migraine attack, to
      successfully self-inject a single dose of sumatriptan using a novel sumatriptan
      auto-injector (Alsuma((r))), and to evaluate the safety, tolerability, and
      effectiveness of this sumatriptan auto-injector during an acute migraine attack.
      BACKGROUND: This sumatriptan auto-injector is a single-use system for the rapid
      subcutaneous delivery of 6 mg of sumatriptan succinate in the acute management of
      migraine pain. This auto-injector was developed to address the clinical need for
      an easy-to-use and rapid-to-administer system that did not require any assembly
      during the time of an ongoing attack. METHODS: This was an open-label, phase 3
      trial conducted at 10 sites in the USA. Male or female adults, ages 18-60 years
      old, were eligible for study entry if they met International Headache Society
      criteria for migraine with or without aura, with at least 2 attacks per month,
      and if they reported use of subcutaneous injectable sumatriptan on at least 2
      occasions within the previous 2 months. During the onset of a migraine attack of
      moderate-to-severe intensity, patients were asked to administer a 6-mg
      subcutaneous dose of sumatriptan using the auto-injector. Patients returned to
      the study site within 72 hours of the migraine for the post-treatment assessment
      visit. RESULTS: A total of 63 patients met entry criteria and received a dose of
      study medication (the intent-to-treat sample). Sixty-one patients (96.8%)
      reported injection in the thigh, and 2 patients (3.2%) reported injection in the
      arm. On the patient questionnaire, 100% of patients (95% confidence interval [CI]
      94.3-100%) "agreed" or "agreed strongly" that the written instructions for the
      auto-injector were clear and easy to follow (30.2% "agreed"; 69.8% "agreed
      strongly"); 95.2% of patients (95% CI 86.7-99.0%) found that the auto-injector
      was easy to use (36.5% "agreed"; 58.7% "agreed strongly"), and 65.1% of patients
      (95% CI 52.0-76.7%) stated that they preferred the new auto-injector to the
      traditional auto-injector that they were using prior to study entry (42.9%
      "agreed"; 22.2% "agreed strongly"). Headache response rate at 2 hours was 93.7%
      (95% CI 84.5-98.2%), and pain-free rate at 2 hours was 60.3% (95% CI 47.2-72.4%).
      Pain-free rates at 2 hours were similarly high (58.3%; 95% CI 36.6-77.9%) in the
      subgroup of patients reporting severe baseline headache pain. Only 1 patient
      reported use of rescue medication after use of the auto-injector, a single oral
      dose of sumatriptan 100 mg on the same day. The most frequent adverse event was
      injection site bruising, reported by 15.9% of patients, and rated in all instance
      as mild in intensity. The second most frequent adverse event was injection site
      pain, reported by 6.3% of patients, and rated as mild by all patients except 1,
      who rated it as moderate in intensity. CONCLUSION: The majority of injection
      experienced patients reported the pre-assembled, single-use sumatriptan auto
      injector to be an easy-to-use, preferred treatment for an acute migraine attack.
      The study found the auto-injector to be safe and well tolerated, with levels of
      injection site reactions that were mild and infrequent.

PMID- 23148800
TI  - Linker-based control of electron propagation through ferrocene moieties
      covalently anchored onto insulator-based nanopores derived from a polystyrene
      poly(methylmethacrylate) diblock copolymer.
AB  - This paper reports the effects of linker length on electron propagation through
      ferrocene moieties covalently anchored onto insulator-based cylindrical nanopores
      derived from a cylinder-forming polystyrene-poly(methylmethacrylate) diblock
      copolymer. These nanopores (24 nm in diameter, 30 nm long) aligned perpendicular
      to an underlying gold electrode were modified via esterification of their surface
      COOH groups with OH-terminated ferrocene derivatives having different alkyl
      linkers (FcCO(CH(2))(n)OH; n = 2, 5, 15). Cyclic voltammograms were measured in
      0.1 M NaBF(4) at different scan rates to assess the efficiency of electron
      propagation through the ferrocene moieties. The redox peaks of the anchored
      ferrocenes were observed at nanoporous films decorated with FcCO(CH(2))(15)OH and
      FcCO(CH(2))(5)OH, but not at those with FcCO(CH(2))(2)OH. Importantly, the higher
      electron propagation efficiency was observed in the use of the longer linker, as
      shown by the apparent diffusion coefficients (ca. 10(-12) cm(2)/s for n = 15; ca.
      10(-13) cm(2)/s for n = 5; no electron propagation for n = 2). The observed
      electron propagation resulted from electron hopping across relatively large
      spacing that was controlled by the motion of anchored redox sites (bounded
      diffusion). The longer linker led to the larger physical displacement range of
      anchored ferrocene moieties, facilitating the approach of the adjacent ferrocene
      moieties within a distance required for electron self-exchange reaction. The
      linker-based control of redox-involved electron propagation on nanostructured,
      insulating surfaces will provide a means for designing novel molecular
      electronics and electrochemical sensors.

PMID- 23148801
TI  - Safe thyroidectomy with intraoperative methylene blue spraying.
AB  - BACKGROUND: We aimed to minimalize operative complications by spraying of
      methylene blue stain on thyroid glands and the perithyroidal area. MATERIAL AND
      METHODS: The intra-operative methylene blue spraying technique was used
      prospectively on a total of 56 patients who had undergone primary (not recurrent)
      thyroid surgery for a variety of thyroid diseases. Bilateral total thyroidectomy
      was performed in all cases. After superior but before inferior pole ligation,
      0.5ml of methylene blue was sprayed over the thyroid lobe and perilober area.
      Tissues, especially parathyroides, the recurrent laryngeal nerve, and the
      inferior thyroid artery, were identified and evaluated. RESULTS: Recurrent
      laryngeal nerve and arteries were not stained and thus they remained white in all
      cases while all other tissues were stained blue. Within three minutes parathyroid
      glands washed out the blue stain and the original yellow color was regained.
      Thyroid tissue wash-out time was not less than 15 minutes; perithyroideal
      muscles, tendinous and lipoid structures took no less than 25 minutes.
      CONCLUSION: The safety of intravascular methylene blue guidance on thyroid
      surgery is known. This research demonstrates the effectiveness of the spraying
      technique, a new technique which ensures not only identification of parathyroid
      glands within three minutes, but also identification of recurrent laryngeal
      nerves and inferior thyroid arteries.

PMID- 23148802
TI  - Heterologous production of 4-O-demethylbarbamide, a marine cyanobacterial natural
      product.
AB  - Heterologous expression of the barbamide biosynthetic gene cluster, obtained from
      the marine cyanobacterium Moorea producens, in the terrestrial actinobacterium
      Streptomyces venezuelae, resulted in the production of a new barbamide congener 4
      O-demethylbarbamide, demonstrating the potential of this approach for
      investigating the assembly and tailoring of complex marine natural products.

PMID- 23148803
TI  - Posttraumatic stress disorder in veterans and military personnel: epidemiology,
      screening, and case recognition.
AB  - Posttraumatic stress disorder (PTSD) is a psychiatric disorder that affects 7-8%
      of the general U.S. population at some point during their lifetime; however, the
      prevalence is much higher among certain subgroups, including active duty military
      personnel and veterans. In this article, we review the empirical literature on
      the epidemiology and screening of PTSD in military and veteran populations,
      including the availability of sensitive and reliable screening tools. Although
      estimates vary across studies, evidence suggests that the prevalence of PTSD in
      deployed U.S. military personnel may be as high as 14-16%. Prior studies have
      identified trauma characteristics and pre- and posttrauma factors that increase
      risk of PTSD among veterans and military personnel. This information may help to
      inform prevention and screening efforts, as screening programs could be targeted
      to high-risk populations. Large-scale screening efforts have recently been
      implemented by the U.S. Departments of Defense and Veterans Affairs. Given the
      prevalence and potential consequences of PTSD among veterans and active duty
      military personnel, development and continued evaluation of effective screening
      methods is an important public health need.

PMID- 23148804
TI  - Retinoids in the chemoprevention of non-melanoma skin cancers: why, when and how.
AB  - INTRODUCTION: The chemoprevention refers to the use of various types of chemical
      agents for preventing carcinogenic progression. Systemic retinoids are the most
      studied chemopreventive agents due to their capacity to regulate cell
      proliferation and their demonstrated efficacy in several clinical studies.
      OBJECTIVES: The aim of the authors was to give precise indications regarding the
      use of the systemic retinoid in the chemoprevention of non-melanoma skin cancer
      (NMSC). METHODS: The authors reviewed the literature found through a search to
      MEDLINE (from 2001 to December 2011). RESULTS: Both acitretin and isotretinoin
      are effective for the prevention of NMSC. Isotretinoin is preferred in xeroderma
      pigmentosum and nevoid basal cell carcinoma syndrome, whereas acitretin is more
      used in transplant recipients, psoriasis and severe sun damage. CONCLUSION:
      Despite numerous studies of the literature concerning retinoids in
      chemoprevention of NMSC, precise details of the type of retinoid to use, dosage
      and the duration of this preventive treatment and how to manage side effects in
      the case of long-lasting treatment are still not uniform and comparable.
      Moreover, neither guidelines nor approval by Food and Drug Administration exist
      to regulate the use of retinoids in chemoprevention.

PMID- 23148805
TI  - Are we witnessing the decline effect in the Type D personality literature? What
      can be learned?
AB  - After an unbroken series of positive, but underpowered studies seemed to
      demonstrate Type D personality predicting mortality in cardiovascular disease
      patients, initial claims now appear at least exaggerated and probably false.
      Larger studies with consistently null findings are accumulating. Conceptual,
      methodological, and statistical issues can be raised concerning the construction
      of Type D personality as a categorical variable, whether Type D is sufficiently
      distinct from other negative affect variables, and if it could be plausibly
      assumed to predict mortality independent of depressive symptoms and known
      biomedical factors, including disease severity. The existing literature
      concerning negative affect and health suggests a low likelihood of discovering a
      new negative affect variable that independently predicts mortality better than
      its many rivals. The apparent decline effect in the Type D literature is
      discussed in terms of the need to reduce the persistence of false positive
      findings in the psychosomatic medicine literature, even while preserving a
      context allowing risk-taking and discovery. Recommendations include greater
      transparency concerning research design and analytic strategy; insistence on
      replication with larger samples before accepting "discoveries" from small
      samples; reduced confirmatory bias; and availability of all relevant data. Such
      changes would take time to implement, face practical difficulties, and run
      counter to established practices. An interim solution is for readers to maintain
      a sense of pre-discovery probabilities, to be sensitized to the pervasiveness of
      the decline effect, and to be skeptical of claims based on findings reaching
      significance in small-scale studies that have not been independently replicated.

PMID- 23148806
TI  - Scientific inbreeding and same-team replication: type D personality as an
      example.
AB  - Replication is essential for validating correct results, sorting out false
      positive early discoveries, and improving the accuracy and precision of estimated
      effects. However, some types of seemingly successful replication may foster a
      spurious notion of increased credibility, if they are performed by the same team
      and propagate or extend the same errors made by the original discoveries. Besides
      same-team replication, replication by other teams may also succumb to inbreeding,
      if it cannot fiercely maintain its independence. These patterns include obedient
      replication and obliged replication. I discuss these replication patterns in the
      context of associations and effects in the psychological sciences, drawing from
      the criticism of Coyne and de Voogd of the proposed association between type D
      personality and cardiovascular mortality and other empirical examples.

PMID- 23148807
TI  - Suicide risk in multiple sclerosis: a systematic review of current literature.
AB  - BACKGROUND: Studies have shown that suicidal ideation is often revealed among
      patients suffering from Multiple Sclerosis (MS). Mental health assessment of
      physically ill patients should form part of routine clinical evaluation,
      particularly in chronic illness. OBJECTIVE: The aim of the present paper was to
      investigate whether there was a relationship between MS and suicidal behavior.
      METHODS: A systematic review of the literature was conducted to determine the
      potential association between MS and suicidal behavior. A total of 12 articles
      from peer-reviewed journals were considered and selected for this review.
      RESULTS: Most studies have documented a higher suicide rate in patients with MS
      compared to the general population, and suicide was associated with several risk
      factors: Depression severity, social isolation, younger age, progressive disease
      subtype, lower income, earlier disease course, higher levels of physical
      disability, and not driving. CONCLUSIONS: Clinicians should be aware of the fact
      that suicidality may occur with higher frequency in MS patients, the available
      data suggest that the risk of self-harm is higher than expected in MS patients.

PMID- 23148808
TI  - Anxiety and risk of type 2 diabetes: evidence from the Baltimore Epidemiologic
      Catchment Area Study.
AB  - OBJECTIVE: Depression is increasingly recognized as a risk factor for type 2
      diabetes, and is also commonly comorbid with anxiety. However, few studies have
      examined whether anxiety is predictive of diabetes risk. The objectives of this
      study are to examine the prospective relationship between anxiety disorders
      (generalized anxiety disorder, panic disorder, social phobia, and agoraphobia)
      and risk of type 2 diabetes over an 11-year period, and to investigate the
      association between anxiety and risk of diabetes-related complications among
      those with prevalent type 2 diabetes. METHODS: Data come from the 1993/6 and
      2004/5 waves of the Baltimore Epidemiologic Catchment Area Study (N=1920), a
      population-based prospective cohort. Anxiety disorders were assessed using the
      Diagnostic Interview Schedule. The prospective association between anxiety and
      incident type 2 diabetes was evaluated using a series of nested multivariable
      logistic regression models. RESULTS: At baseline, 315 participants (21.8%) had an
      anxiety disorder. The relationship between anxiety and risk of developing type 2
      diabetes was not statistically significant after controlling for demographic
      characteristics (Odds Ratio (OR): 1.28, 95% Confidence Interval (CI): 0.75,
      2.18). There was no relationship between anxiety and diabetes risk after
      controlling for health behaviors and depression status (OR: 1.00, 95% CI: 0.53,
      1.89). There was no significant relationship between anxiety and development of
      diabetes-related complications among those with prevalent type 2 diabetes (OR:
      2.02, 95% CI: 0.61, 6.74). CONCLUSION: Anxiety disorders are not associated with
      increased risk of type 2 diabetes or risk of diabetes complications among those
      who have diabetes.

PMID- 23148809
TI  - Cognitive-behavioural factors that predict sleep disturbance 4 years later.
AB  - OBJECTIVE: Cognitive models have identified a number of factors that maintain
      sleep disturbance. It is unknown whether similar factors lead to initial onset.
      This study tested whether three cognitive-behavioural factors: ruminative style,
      somatic sensitivity, and behavioural avoidance predicted sleep disturbance onset
      at four-year follow-up. METHODS: Participants (n=4,042) were assessed using a) a
      composite measure of Somatic Sensitivity, b) the Ruminative Style Scale, c) the
      Behavioural Inhibition Scale of the BISBAS and d) sleep-related items from the
      Goldberg Depression and Anxiety Scale. RESULTS: Sleep disturbance at 4 years was
      significantly predicted by all three cognitive-behavioural factors--somatic
      sensitivity, ruminative style and behavioural avoidance--and, in the final
      analysis, was independently predicted by somatic sensitivity (OR=1.427, p<0.001)
      and ruminative style (OR=1.035, p=0.002). CONCLUSION: This study tested whether
      three cognitive-behavioural factors: ruminative style, somatic sensitivity, and
      behavioural avoidance were predictive of the onset of sleep disturbance after 4
      years. Although all three factors were significantly associated with the onset of
      sleep disturbance, only ruminative style and somatic sensitivity were found to
      independently predict sleep disturbance, supporting these constructs as
      predisposing cognitive-behavioural risk factors.

PMID- 23148810
TI  - Sleep problems as a mediator of the association between parental education
      levels, perceived family economy and poor mental health in children.
AB  - OBJECTIVE: The aim of this study was to investigate the association between
      familial socioeconomic status (SES) and children's sleep problems, and the role
      of sleep problems as a mediator between familial SES and childhood mental health
      problems. METHODS: Participants were 5781 11-13 year old children from the Bergen
      Child Study. Data were collected on family economy, parental education, and
      children's difficulties initiating and/or maintaining sleep (DIMS), time in bed
      (TIB) and self-reported mental health problems using the Strengths and
      Difficulties Questionnaire (SDQ). RESULTS: Sleep problems were significantly more
      common in children from lower SES families. Children from families with poor and
      average perceived family economy had significantly higher odds of reporting DIMS
      compared to children from families with very good economy (ORs=3.5 and 1.7,
      respectively). The odds were reduced by 12-36% adjusting for poor parental health
      and single parenting, but remained significant. Children from families with a
      poor economy had increased odds of a short TIB, both in the crude model (OR=1.9)
      and adjusted for parental characteristics (OR=2.2). Maternal education level was
      significantly associated with short TIB. Path analysis was conducted to
      investigate the potential mediating role of DIMS in the relationship between SES
      and mental health. The significant direct association between perceived family
      economy and SDQ total problems score was partially mediated by a significant
      indirect effect of sleep problems. CONCLUSION: Sleep problems are common among
      children from families with a lower SES and may be a potential mechanism through
      which low SES is translated into mental health problems.

PMID- 23148811
TI  - Abdominal pain in British young people: associations, impairment and health care
      use.
AB  - OBJECTIVE: To assess the frequency and associations of abdominal pain in a sample
      of British secondary school young people and to examine predictors of impairment
      and health care use. METHODS: Cross-sectional study of young people aged 11-16
      years that completed questionnaires documenting abdominal pain, related
      impairment and health care consultations. They also provided information
      detailing other physical symptoms, health problems and mental health status.
      RESULTS: 1173 students completed questionnaires; 598 (53%) reported abdominal
      pains in the previous 3 months (15% >once a week). Pains were significantly
      linked to reporting medical illness, to high levels of a broad range of physical
      symptoms and with students deeming these symptoms to be stress/mood sensitive.
      They were also linked to depressive and other emotional and behavioural problems
      and with medical help seeking (seeing a health professional in the previous year
      and contact ever with mental health practitioners). Considerable impairment was
      reported by 36%; this was independently predicted by abdominal pain frequency,
      higher levels of concurrent physical symptoms and symptom stress/mood
      sensitivity. In 18% of students the abdominal pains had led to medical
      consultations; this was independently predicted by pain related impairment.
      CONCLUSIONS: Frequent abdominal pains are common in British secondary school
      adolescents; they are linked to emotional symptoms and are often impairing and
      lead to medical consultations. Impairment was associated not only to pain
      frequency but also to reporting other physical symptoms and symptom stress/mood
      sensitivity, and impairment was a strong predictor of medical help seeking.

PMID- 23148812
TI  - The late positive potential as a marker of motivated attention to underweight
      bodies in girls with anorexia nervosa.
AB  - OBJECTIVE: In anorexia nervosa (AN), aspects of motivational salience and reward
      are increasingly discussed. Event related potentials, particularly the late
      positive potential (LPP), have been investigated as a marker for motivational
      salience of stimuli, for example in addictive disorders. The aim of this study
      was to assess the LPP as a possible indicator of motivated attention towards
      disease-specific pictures of underweight female bodies in adolescents with AN in
      comparison to typically developing (TD) adolescent girls. METHOD: 13 girls with
      AN and 18 TD adolescent girls (aged 12 to 18 years) viewed pictures of
      underweight, normal-weight and overweight women while EEG activity was recorded.
      An earlier (450-680 ms after stimulus onset) as well as a later time window (850
      1250 ms after stimulus onset) of the LPP were examined for the different picture
      categories. Participants were also asked to rate subjective emotions (fear,
      disgust, happiness) elicited by the pictures. RESULTS: Subjective ratings showed
      no differential experience of emotions for the two groups. For AN patients,
      highest LPP amplitudes were found for underweight women in the earlier as well as
      in the later time window. In TD girls, highest amplitudes for pictures of
      overweight women were observed in the earlier time window. CONCLUSION: A
      differential LPP pattern for girls with AN and TD girls when viewing pictures of
      women's bodies of different weight categories was obtained. Highest amplitudes in
      AN patients for pictures of underweight women may reflect motivational
      significance of strongly underweight body shapes.

PMID- 23148813
TI  - Characteristics, treatments and outcome of psychosis in Thai SLE patients.
AB  - OBJECTIVES: To study the clinical characteristics and outcomes of psychosis and
      its clinical correlation with disease activity in Thai systemic lupus
      erythematosus (SLE) patients. METHODS: From 750 SLE patients, 36 episodes of
      psychosis or psychotic depression in SLE patients were retrospectively identified
      between June 1999 and June 2009 at Srinagarind Hospital, Khon Kaen University.
      The clinical characteristics, laboratory analyses, disease activity, treatments
      and outcomes were studied. RESULTS: A total of 35 SLE patients had 36 psychotic
      episodes that consisted of 29 psychotic episodes and 7 psychotic depressive
      episodes. Eleven episodes (30.6%) occurred during the first manifestation of
      lupus. Psychotic symptoms included persecutory delusion (50%), bizarre delusion
      (44.4%), third person auditory hallucinations (44.4%) and visual hallucinations
      (36.1%). Twenty four episodes (67%) were associated with active lupus in CNS and
      other organs. All patients received immunotherapy and psychotropic treatments.
      Psychosis and depressive psychosis were treated with antipsychotics and
      antidepressants for a mean duration of 71 and 410 days. One death resulted from
      suicide, and one of thirty four cases (2.9%) had a reoccurrence within a mean
      follow-up period of 44 months. CONCLUSION: About one-third of the psychotic
      episodes occurred during the first manifestation of lupus. Persecutory delusion,
      bizarre delusion, third person auditory hallucination, and visual hallucination
      were common. During psychotic episodes, lupus activity was active in other parts
      of CNS and organs in 67% of patients. Depressive psychosis required psychotropic
      treatment longer than psychosis alone. The psychiatric outcome was very
      favorable. Most of psychotic episodes (97.1%) were fully remitted and rarely
      showing recurrences.

PMID- 23148814
TI  - Acute pain speeds skin barrier recovery in healthy men and women.
AB  - OBJECTIVE: Psychological stress is known to impair skin barrier recovery, but
      little is known about the impact of pain on skin healing processes. Our primary
      goals were to examine the degree to which acute pain affects recovery from skin
      barrier disruption, and the potential mediating impact of cortisol and
      catecholamines. METHODS: Healthy non-smokers aged 18-43 (N = 53, 65% women)
      underwent a 3-minute cold pressor pain stimulus to their foot. Tape-stripping of
      forearm skin occurred at two separate locations: before (site 1) and after (site
      2) the pain stimulus. Transepidural water loss (TEWL) was assessed at baseline
      (pre-stripping), immediately post-stripping, and at 75 min to determine skin
      barrier recovery. Cortisol and catecholamine responses were obtained from
      multiple saliva and plasma samples, respectively. RESULTS: Contrary to
      expectations, greater pain was associated with faster skin barrier recovery, even
      after controlling for demographics, mood, anxiety, and other factors. Those who
      reported higher pain showed faster recovery at site 2 compared to a) individuals
      who experienced lower pain; and b) their own recovery at site 1. Greater increase
      in norepinephrine (but not in cortisol) was also associated with faster recovery
      at site 2, and mediated the impact of pain on recovery. DISCUSSION: Results
      bolster evidence that acute pain can affect immune-related processes. It is
      possible that acute pain may speed recovery from dermal abrasions, although pain
      is likely to impair recovery from more severe wounds. As pain is an important
      potential target for clinical intervention, further investigation of pain,
      stress, and healing processes is warranted.

PMID- 23148815
TI  - Body image as a predictor of psychopathology in surgical patients with colorectal
      disease.
AB  - OBJECTIVE: This study aimed to test the relevance of a cognitive behavioural
      model of body image in a prospective study of colorectal surgery patients and to
      determine if pre-existing body image disturbance influenced psychological
      adjustment following surgery. METHODS: Sixty-seven adult consecutive colorectal
      surgery patients completed measures assessing psychopathology, body image related
      beliefs and health related quality of life during pre-admission for surgery using
      a questionnaire battery. Each participant was followed up three months after
      surgery. RESULTS: Depression and anxiety were positively correlated with body
      image disturbance and self evaluation at baseline. Those patients who went on to
      receive stomas experienced a significant deterioration in their body image that
      was not observed in those whose surgery did not result in the formation of a
      stoma. In the regression analysis, body image disturbance was a significant
      predictor of baseline levels of depression and emotional quality of life. Initial
      levels of body image disturbance remained a significant predictor of depression
      and anxiety at follow up assessment after medical variables and baseline levels
      of depression and anxiety, respectively, had been controlled for. CONCLUSION: Our
      findings support the hypothesis that pre-existing vulnerabilities in body image
      influence emotional adjustment during the recovery phase following surgery.
      Further research on screening for body image disturbance in surgical patients in
      order to promote adjustment is warranted.

PMID- 23148816
TI  - Psychological impact and risk factors associated with new onset fecal
      incontinence.
AB  - OBJECTIVES: We aim to evaluate the psychological impact and risk factors
      associated with new onset FI over 12 years in adults over 18 years for the first
      time in a population-based study. METHODS: Participants (n = 1775) were a random
      population sample from Penrith, Australia who responded to a survey in 1997 and
      completed a 12-year follow-up survey (response rate = 60%). FI was defined as
      having leakage of stool over the past 12 months. The original and follow-up
      surveys contained valid questions on demographic, gastrointestinal and
      psychological symptoms. RESULTS: 114 (11.4%) reported new onset FI at the 12 year
      follow-up. People who reported FI at the 12 year follow-up were significantly
      more anxious and depressed. In terms of baseline risk factors only bloating (OR =
      1.3; 95%CI 1.0-1.6, P = 0.026) was an independent predictor of developing new
      onset FI. However, current bowel symptoms measured at follow-up including less
      likelihood of <3 bowel motions a week, increased urgency and mucus were
      independently associated with having FI at follow-up. CONCLUSION: FI is
      associated with anxiety and depression. Baseline GI symptoms do not appear to be
      as important as current bowel symptoms in determining who develops FI.

PMID- 23148817
TI  - Fatigue and disease-related worries among inflammatory bowel disease patients in
      remission; is it a reflection of coexisting IBS-like symptoms? A short report.
AB  - OBJECTIVES: Irritable bowel syndrome (IBS) like symptoms and fatigue are
      frequently reported in quiescent inflammatory bowel disease (IBD). We
      hypothesized that coexisting IBS-like symptoms might be associated with increased
      levels of fatigue and disease-related worries. METHODS: A total of 140 IBD
      outpatients were assessed. Cut-off for remission was <4 and <3 on the disease
      activity indices SCDAI and SCCAI. In addition patients on current steroid
      treatment were excluded. A diagnosis of IBS was based on the Rome criteria.
      Fatigue was measured with the Fatigue Questionnaire (FQ), disease related worries
      with the Rating Form of IBD Patient Concerns (RFIPC). RESULTS: Eighty-nine
      patients fulfilled the criteria for remission. Of these 89 patients, 21 and 30
      were IBS positive according to the Rome II and III criteria, respectively. FQ
      scores were significantly elevated in IBS positive UC patients. Clinical
      significant differences were also found in relation to RFIPC scores. CONCLUSION:
      Coexisting IBS-like symptoms among IBD patients in remission are associated with
      an increased level of fatigue and disease-related worries.

PMID- 23148818
TI  - Emotional coping is a better predictor of cardiac prognosis than depression and
      anxiety.
AB  - OBJECTIVE: We compared, in a prospective study on patients with acute coronary
      syndrome, the predictive effect of a depression or anxiety diagnosis and of
      emotion-focused, problem-focused and dysfunctional coping strategies, as detected
      early after an acute event, on patients' left ventricular ejection fraction
      (LVEF), a reliable prognostic index of disease severity, at a three-month follow
      up. METHODS: Ninety consecutive patients following an acute coronary syndrome
      event (83.3% men; mean age 56.9 +/- 8.9 years) were included in the study.
      Demographic and clinical characteristics, presence of depression and anxiety
      disorders (MINI), and active use of emotion-focused, problem-focused and
      dysfunctional coping strategies (Brief Cope) were assessed at the time of
      enrolment. LVEF at a three-month follow up was used as the outcome measure.
      RESULTS: The medical predictors of LVEF accounted for 10.6% of the variance of
      LVEF at follow up. Emotion-focused coping strategies significantly contributed
      for an additional 6.1%, while the presence of a depression and/or anxiety
      disorder was not a significant predictor of LVEF at follow up, nor were
      dysfunctional and problem-focused coping strategies. CONCLUSION: Emotion-focused
      coping strategies at the time of the cardiac event were the only reliable
      psychological predictor of disease severity at a three-month follow up. These
      findings hint to the possibility that variables such as emotional coping may be a
      fruitful target for psychological treatments directed at cardiac patients in
      primary care settings.

PMID- 23148819
TI  - Financial impact of accurate discharge coding in a liaison psychiatry service.
AB  - OBJECTIVE: Previous research has shown that patients seen by liaison psychiatry
      services are a complex and expensive patient group and that the psychiatric co
      morbidities of hospital inpatients are poorly attested at discharge for
      assignment to diagnosis-related groups (DRGs). The aim of this study was to
      investigate the accuracy of discharge coding in a neuropsychiatry liaison
      population. We also aimed to establish whether or not, had the correct diagnosis
      been assigned, additional funding would have been allocated to the hospital.
      METHODS: Diagnostic codes were retrospectively collected from the discharge
      diagnoses for all inpatients (n=276) referred to the neuropsychiatry liaison
      service in a university hospital over a 12 month period and these were compared
      to a consensus diagnosis. Using grouper software, codes were then changed to
      reflect the consensus diagnoses and DRGs were recalculated to see if the change
      in diagnosis led to a change in reimbursement for those patients. RESULTS:
      Discharge diagnosis and consensus diagnosis were in agreement in 30% of cases.
      When discharge codes were corrected, patients changed to a higher paying DRG in
      28/220 (12.7%) of patients. The increase in costing associated with this change
      in DRG was ?305,349. CONCLUSIONS: According to these results, not only is the
      complexity of patients seen by psychiatry consult services in general hospitals
      not reflected in the discharge diagnosis, but, in this sample of patients, the
      additional complexity would have led to a significant increase in reimbursement
      to the hospital. Further training of doctors should increase awareness of this
      important issue.

PMID- 23148820
TI  - Symptoms of migraine and its relationship to personality disorder in a non
      patient sample.

PMID- 23148821
TI  - Comparison of prevalence estimation of Mycobacterium avium subsp.
      paratuberculosis infection by sampling slaughtered cattle with macroscopic
      lesions vs. systematic sampling.
AB  - The objective of this study was to identify the most reliable approach for
      prevalence estimation of Mycobacterium avium ssp. paratuberculosis (MAP)
      infection in clinically healthy slaughtered cattle. Sampling of macroscopically
      suspect tissue was compared to systematic sampling. Specimens of ileum, jejunum,
      mesenteric and caecal lymph nodes were examined for MAP infection using bacterial
      microscopy, culture, histopathology and immunohistochemistry. MAP was found most
      frequently in caecal lymph nodes, but sampling more tissues optimized the
      detection rate. Examination by culture was most efficient while combination with
      histopathology increased the detection rate slightly. MAP was detected in 49/50
      animals with macroscopic lesions representing 1.35% of the slaughtered cattle
      examined. Of 150 systematically sampled macroscopically non-suspect cows, 28.7%
      were infected with MAP. This indicates that the majority of MAP-positive cattle
      are slaughtered without evidence of macroscopic lesions and before clinical signs
      occur. For reliable prevalence estimation of MAP infection in slaughtered cattle,
      systematic random sampling is essential.

PMID- 23148823
TI  - Mosquito ecology and control of malaria.
AB  - Mosquitoes transmit some of the most important infectious diseases of man
      including malaria that today kills around 0.6-1.2 million people a year, the
      majority children in low-income countries. There is increasing realisation that
      no single intervention is likely to halt malaria and a multipronged approach is
      needed including vector control. Very effective vector control measures are
      currently available, most involving insecticides, although there is evidence of
      growing problems with the spread of resistance. A variety of novel genetic
      approaches to vector control are under active development. Research on targeting
      the mosquito has been greatly facilitated by huge investment in molecular
      resources, including the provision of numerous full-genome sequences. Vector
      control is applied population biology, and I argue here that further progress
      will require as much attention to mosquito ecology as has been paid to mosquito
      molecular biology.

PMID- 23148825
TI  - Protein-protein interactions between the bilirubin-conjugating UDP
      glucuronosyltransferase UGT1A1 and its shorter isoform 2 regulatory partner
      derived from alternative splicing.
AB  - The oligomerization of UGTs [UDP (uridine diphosphate)-glucuronosyltransferases]
      modulates their enzyme activities. Recent findings also indicate that
      glucuronidation is negatively regulated by the formation of inactive oligomeric
      complexes between UGT1A enzymes [i1 (isoform 1)] and an enzymatically inactive
      alternatively spliced i2 (isoform 2). In the present paper, we assessed whether
      deletion of the UGT-interacting domains previously reported to be critical for
      enzyme function might be involved in i1-i2 interactions. The bilirubin
      conjugating UGT1A1 was used as a prototype. We also explored whether
      intermolecular disulfide bonds are involved in i1-i2 interactions and the
      potential role of selected cysteine residues. Co-immunoprecipitation assays
      showed that UGT1A1 lacking the SP (signal peptide) alone or also lacking the
      transmembrane domain (absent from i2) did not self-interact, but still interacted
      with i2. The deletion of other N- or C-terminal domains did not compromise i1-i2
      complex formation. Under non-reducing conditions, we also observed formation of
      HMWCs (high-molecular-mass complexes) for cells overexpressing i1 and i2. The
      presence of UGTs in these complexes was confirmed by MS. Mutation of individual
      cysteine residues throughout UGT1A1 did not compromise i1-i1 or i1-i2 complex
      formation. These findings are compatible with the hypothesis that the interaction
      between i1 and i2 proteins (either transient or stable) involves binding of more
      than one domain that probably differs from those involved in i1-i1 interactions.

PMID- 23148822
TI  - The efficacy of vigorous-intensity exercise as an aid to smoking cessation in
      adults with elevated anxiety sensitivity: study protocol for a randomized
      controlled trial.
AB  - BACKGROUND: Although cigarette smoking is a leading cause of death and disability
      in the United States (US), over 40 million adults in the US currently smoke.
      Quitting smoking is particularly difficult for smokers with certain types of
      psychological vulnerability. Researchers have frequently called attention to the
      relation between smoking and anxiety-related states and disorders, and evidence
      suggests that panic and related anxiety vulnerability factors, specifically
      anxiety sensitivity (AS or fear of somatic arousal), negatively impact cessation.
      Accordingly, there is merit to targeting AS among smokers to improve cessation
      outcome. Aerobic exercise has emerged as a promising aid for smoking cessation
      for this high-risk (for relapse) group because exercise can effectively reduce AS
      and other factors predicting smoking relapse (for example, withdrawal, depressed
      mood, anxiety), and it has shown initial efficacy for smoking cessation. The
      current manuscript presents the rationale, study design and procedures, and
      design considerations of the Smoking Termination Enhancement Project (STEP).
      METHODS: STEP is a randomized clinical trial that compares a vigorous-intensity
      exercise intervention to a health and wellness education intervention as an aid
      for smoking cessation in adults with elevated AS. One hundred and fifty eligible
      participants will receive standard treatment (ST) for smoking cessation that
      includes cognitive behavioral therapy (CBT) and nicotine replacement therapy
      (NRT). In addition, participants will be randomly assigned to either an exercise
      intervention (ST+EX) or a health and wellness education intervention (ST+CTRL).
      Participants in both arms will meet 3 times a week for 15 weeks, receiving CBT
      once a week for the first 7 weeks, and 3 supervised exercise or health and
      wellness education sessions (depending on randomization) per week for the full 15
      week intervention. Participants will be asked to set a quit date for 6 weeks
      after the baseline visit, and smoking cessation outcomes as well as putative
      mediator variables will be measured up to 6 months following the quit date.
      DISCUSSION: The primary objective of STEP is to evaluate whether vigorous
      intensity exercise can aid smoking cessation in anxiety vulnerable adults. If
      effective, the use of vigorous-intensity exercise as a component of smoking
      cessation interventions would have a significant public health impact.
      Specifically, in addition to improving smoking cessation treatment outcome,
      exercise is expected to offer benefits to overall health, which may be
      particularly important for smokers. The study is also designed to test putative
      mediators of the intervention effects and therefore has the potential to advance
      the understanding of exercise-anxiety-smoking relations and guide future research
      on this topic. CLINICAL TRIALS REGISTRY: ClinicalTrials.gov, NCT01065506,
      http://clinicaltrials.gov/ct2/show/NCT01065506.

PMID- 23148826
TI  - Intra-medullary tuberculoma of the spinal cord presenting with typhoid and
      paraplegia: a case report.
AB  - INTRODUCTION: Intra-medullary spinal tuberculoma is a rare form of tuberculosis,
      with an incidence of only two in 100,000 patients with tuberculosis. We present a
      case of intra-medullary tuberculoma from Pakistan, which was diagnosed by
      radiological findings and analysis of cerebrospinal fluid using polymerase chain
      reaction testing. CASE PRESENTATION: We present the case of a 28-year-old Sindhi
      male with intra-medullary tuberculoma of the spinal cord at the C3 level. Our
      patient was treated solely with anti-tubercular drug therapy with no surgical
      intervention. CONCLUSIONS: We discuss the possible clinical management of such
      rare cases, considering both chemotherapeutic and surgical options. Additionally,
      diagnostic procedures and findings are discussed; we suggest cerebrospinal fluid
      analysis via polymerase chain reaction and gadolinium-diethylenetriamine
      pentaacetic acid magnetic resonance imaging as important chemical and
      radiological tests to be performed in such cases.

PMID- 23148827
TI  - Obesity takes center stage.

PMID- 23148828
TI  - Weight-based stigma and physician bias.

PMID- 23148829
TI  - Does pediatric obesity indicate child neglect?

PMID- 23148831
TI  - It is time for obesity medicine.

PMID- 23148830
TI  - Weight-related denial of insurance for an infant.

PMID- 23148832
TI  - Applying the principles of professionalism to preventing, identifying, and
      treating obesity.

PMID- 23148833
TI  - AMA Code of Medical Ethics' Opinion on Respect for All Patients.

PMID- 23148834
TI  - Weight bias in health care.

PMID- 23148835
TI  - Diagnosing Obesity: Beyond BMI.

PMID- 23148836
TI  - "Can we talk about your weight for a few minutes, mr. Jones?".

PMID- 23148837
TI  - Obesity-related legislation meets american individualism.

PMID- 23148838
TI  - A rationale for policy intervention in reducing obesity.

PMID- 23148840
TI  - Media Portrayal of People Who are Obese.

PMID- 23148839
TI  - What's Wrong with the U.S. Approach to Obesity?

PMID- 23148841
TI  - Plus seating.

PMID- 23148842
TI  - A Call for Collaborative Action against America's Greatest Health Threat.

PMID- 23148843
TI  - Physician BMI and Weight Counseling.

PMID- 23148844
TI  - About the contributors.

PMID- 23148847
TI  - Introduction: exocrine pancreatic insufficiency and pancreatitis.

PMID- 23148845
TI  - A gender-related action of IFNbeta-therapy was found in multiple sclerosis.
AB  - BACKGROUND: Understanding how sexual dimorphism affects the physiological and
      pathological responses of the immune system is of considerable clinical
      importance and could lead to new approaches in therapy. Sexual dimorphism has
      already been noted as an important factor in autoimmune diseases: the aim of this
      study was to establish whether sexual dimorphism in autoimmune diseases is the
      result of differing pathways being involved in the regulation of T-helper (Th)
      cell network homeostasis. METHODS: We focused on sexually dimorphic changes in
      the immune response in multiple sclerosis (MS) patients in order to ascertain how
      these alterations relate to the pathway regulation of the cytokine homeostasis
      and the Th cell networks. We studied antigen presenting cell (APC)-dependent T
      cell activation in groups of healthy subjects, in patients under interferon (IFN)
      beta-therapy and untreated. Cytokines, soluble (s) CD30 and the expanded
      disability status scale (EDSS) were used as biomarkers for T cell differentiation
      and neurological deficit. RESULTS: The data confirm our belief that sexual
      dimorphism in autoimmune diseases is the result of differing pathways that
      regulate Th cell network homeostasis: interleukin (IL) 6 pathways in women and
      IFNgamma pathways in men. Given the increased susceptibility of women to MS and
      the significance of IL6 in the autoimmune process compared to IFNgamma, it is
      logical to assume that IL6 pathways are in some way implicated in the prevalence
      of autoimmune diseases in women. Indeed, our data indicate that IL6 pathways are
      also involved in T regulatory (Treg) cell imbalance and an increase in
      neurological deficit in both men and women groups of MS patients, underlining the
      autoimmune etiology of multiple sclerosis. In further support of differing
      cytokine pathways in men and women, we noted that the efficacy of IFNbeta
      treatment in the re-establishment of Th-network balance and in the delaying of
      the neurological disability progression is linked to the IL6 pathway in women,
      but to the IFNgamma pathway in men. Lastly, we also identified specific gender
      biomarkers for the use in therapy. CONCLUSIONS: The identification of gender
      specific drugs is of considerable importance in translational medicine and will
      undoubtedly lead to more appropriate therapeutic strategies and more successful
      treatment.

PMID- 23148848
TI  - Exocrine pancreatic insufficiency in the dog: historical background, diagnosis,
      and treatment.
AB  - This overview summarizes research performed during the last decades that has had
      an impact on the diagnosis and management of exocrine pancreatic insufficiency
      (EPI) in dogs. Pancreatic acinar atrophy is by far the most common cause for the
      maldigestion signs of canine EPI. The ability to diagnose pancreatic acinar
      atrophy in the subclinical phase before the development of total acinar atrophy
      and manifestation of clinical signs has offered new possibilities to study the
      pathogenesis of the disease. Diagnosis of exocrine pancreatic dysfunction is
      based on typical findings in clinical histories and clinical signs and is
      confirmed with pancreatic function tests. In recent years, the measurement of
      serum canine trypsin-like immunoreactivity has become the most commonly used
      pancreatic function test to diagnose canine EPI. Serum trypsin-like
      immunoreactivity measurement is species- and pancreas-specific. When clinical
      maldigestion signs of EPI appear, enzyme replacement therapy is indicated.
      Despite accurate enzyme supplementation, only a small portion of orally
      administered enzymes are delivered functionally intact into the small intestine.
      In dogs, the highest enzyme activity in the duodenum has been obtained with
      nonenteric-coated supplements: raw chopped pancreas or powdered enzymes. Aside
      from dietary enzyme supplements, dietary changes are often made to improve
      clinical response, but sometimes weight gain and stool quality remain suboptimal.
      Other medications for treatment of gastrointestinal tract signs are often used in
      such dogs with EPI. Antibiotics are the most common adjunctive medication. Of the
      antibiotics administered, tylosin is used in Finland almost exclusively.

PMID- 23148849
TI  - Exocrine pancreatic insufficiency in the dog: breed associations, nutritional
      considerations, and long-term outcome.
AB  - Canine exocrine pancreatic insufficiency (EPI) is an alimentary tract disorder
      causing malabsorption and debilitations in affected individuals. This article
      covers predisposing factors to EPI and response to therapy. Although relatively
      easy to diagnose, knowledge of breed predispositions (and also of those breeds
      where the disease is less common) can guide the clinician. Numerous studies have
      examined therapy for EPI, and a key finding is the variability in response among
      affected dogs. This implies that close monitoring and individual tailoring of
      therapy is needed to maximize the chance of success. Important factors affecting
      outcome are the choice of enzyme preparation, presence of hypocobalaminemia, and
      the response to the first 2 to 3 months of therapy.

PMID- 23148846
TI  - A role for BELLRINGER in cell wall development is supported by loss-of-function
      phenotypes.
AB  - BACKGROUND: Homeodomain transcription factors play critical roles in metazoan
      development. BELLRINGER (BLR), one such transcription factor, is involved in
      diverse developmental processes in Arabidopsis, acting in vascular
      differentiation, phyllotaxy, flower and fruit development. BLR also has a
      redundant role in meristem maintenance. Cell wall remodelling underpins many of
      these processes, and BLR has recently been shown to regulate expression of PECTIN
      METHYL-ESTERASE 5 (PME5), a cell wall modifying enzyme in control of phyllotaxy.
      We have further explored the role of BLR in plant development by analysing
      phenotypes and gene expression in a series of plants over-expressing BLR, and
      generating combinatorial mutants with blr, brevipedicellus (bp), a member of the
      KNOX1 family of transcription factors that has previously been shown to interact
      with blr, and the homeodomain transcription factor revoluta (rev), required for
      radial patterning of the stem. RESULTS: Plants over-expressing BLR exhibited a
      wide range of phenotypes. Some were defective in cell size and demonstrated
      misregulation of genes predominantly affecting cell wall development. Other lines
      with more extreme phenotypes failed to generate lateral organs, consistent with
      BLR repressing transcription in the shoot apex. Cell wall dynamics are also
      affected in blr mutant plants, and BLR has previously been shown to regulate
      vascular development in conjunction with BP. We found that when bp and blr were
      combined with rev, a set of defects was observed that were distinct from those of
      bp blr lines. In these triple mutants xylem development was most strikingly
      affected, resulting in an almost complete lack of vessels and xylem parenchyma
      with secondary thickening. CONCLUSIONS: Our data support a role for BLR in
      ordering the shoot apex and, in conjunction with BP and REV, playing a part in
      determining the composition and organisation of the vascular system. Microarray
      analysis strongly indicates that the striking vascular phenotypes of blr bp rev
      triple mutants and plants over-expressing BLR result from the misregulation of a
      suite of genes, targets of BLR in wild type plants, that determine cell size and
      structure in the developing vasculature.

PMID- 23148850
TI  - Current status of genetic studies of exocrine pancreatic insufficiency in dogs.
AB  - Exocrine pancreatic insufficiency (EPI) is a disorder wherein the pancreas fails
      to secrete adequate amounts of digestive enzymes. In dogs, EPI is usually the
      consequence of an autoimmune disease known as pancreatic acinar atrophy.
      Originally believed to be a simple autosomal recessive disorder, a test-breeding
      recently revealed that EPI has a more complex mode of inheritance. The
      contributions of multiple genes, combined with environmental factors, may explain
      observed variability in clinical presentation and progression of this disease.
      Research efforts aim to identify genetic variations underlying EPI to assist
      breeders in their efforts to eliminate this disease from their breed and provide
      clinicians with new targets for therapeutic intervention and/or disease
      prevention. Genome-wide linkage, global gene expression, and candidate gene
      analyses have failed to identify a major locus or genetic variations in German
      Shepherd Dogs with EPI. Recently, genome-wide association studies revealed
      numerous genomic regions associated with EPI. Current studies are focused on
      alleles of the canine major histocompatibility complex. In this article we review
      findings from scientific investigations into the inheritance and genetic cause(s)
      of EPI in the purebred dog.

PMID- 23148851
TI  - Exocrine pancreatic insufficiency in the cat.
AB  - Exocrine pancreatic insufficiency (EPI) is a syndrome caused by an insufficient
      amount of pancreatic digestive enzymes in the small intestine. Clinical signs
      most commonly reported in cats with EPI are weight loss, loose and voluminous
      stools, steatorrhea, polyphagia, and in some cases a greasy soiling of the hair
      coat in the perianal region. Serum feline trypsin-like immunoreactivity
      concentration is the diagnostic test of choice for the diagnosis of affected
      cats. Treatment of cats with EPI consists of enzyme supplementation with either a
      powdered pancreatic extract or raw pancreas. Most cats with EPI also have
      severely decreased serum cobalamin concentrations and may require lifelong
      parenteral cobalamin supplementation. Most cats respond well to therapy and can
      have a normal life expectancy and quality of life.

PMID- 23148852
TI  - Exocrine pancreatic insufficiency in dogs and cats: online support for
      veterinarians and owners.
AB  - Pet owners increasingly refer to online sources before, during, and after seeking
      veterinary advice for their pets. Although some online information is inaccurate
      or unhelpful, there is much useful material, and we believe much is to be gained
      by directing owners to online material that supports and complements veterinary
      advice. With regard to managing veterinary patients with exocrine pancreatic
      insufficiency (EPI), there is an excellent online community that not only offers
      moral support and practical advice, but also facilitates clinical research and
      fundraising. For genetic diseases like canine EPI that affect primarily young
      animals, but for which a decade or more of treatment can reasonably be expected,
      online support can greatly facilitate optimal lifelong management. In this
      article we provide some information that may be of value when veterinarians
      consider which web sites to recommend to their clients managing patients with
      EPI.

PMID- 23148853
TI  - Acute pancreatitis in dogs: advances in understanding, diagnostics, and
      treatment.
AB  - Acute pancreatitis in dogs is a potentially reversible condition, but in severe
      forms it can cause systemic and local complications. These complications are
      driven by the cytokine, complement, and kinin systems, with the roles of these
      systems along with other substances such as nitric oxide being increasingly
      studied. The intestinal tract and altered pancreatic microcirculation also
      contribute greatly to the perpetuation of disease. Diagnosis remains difficult,
      because the true diagnostic utility of the current tests available is problematic
      to establish. Further understanding of the pathophysiology of this disease has
      opened up new areas of research into optimal treatments. In particular, the role
      of enteral nutrition has been the focus of much attention, and current
      recommendations are to feed earlier in the disease than previously thought.

PMID- 23148854
TI  - Chronic pancreatitis in dogs.
AB  - Chronic pancreatitis used to be considered uncommon in dogs, but recent
      pathological and clinical studies have confirmed that it is in fact a common and
      clinically significant disease. Clinical signs can vary from low-grade recurrent
      gastrointestinal signs to acute exacerbations that are indistinguishable from
      classical acute pancreatitis. Chronic pancreatitis is a significant cause of
      chronic pain in dogs, which must not be underestimated. It also results in
      progressive impairment of endocrine and exocrine function and the eventual
      development of diabetes mellitus or exocrine pancreatic insufficiency or both in
      some affected dogs at end stage. The etiology is unknown in most cases. Chronic
      pancreatitis shows an increased prevalence in certain breeds, and recent work in
      English Cocker Spaniels suggests it is part of a polysystemic immune-mediated
      disease in this breed. The histological and clinical appearance is different in
      different breeds, suggesting that etiologies may also be different. Diagnosis is
      challenging because the sensitivities of the available noninvasive tests are
      relatively low. However, with an increased index of suspicion, clinicians will
      recognize more cases that will allow them to institute supportive treatment to
      improve the quality of life of the patient.

PMID- 23148855
TI  - Pancreatitis in cats.
AB  - Pancreatitis was considered a rare disease in the cat until a couple of decades
      ago when several retrospective studies of severe acute pancreatitis were
      published. It was apparent that few of the diagnostic tests of value in the dog
      were helpful in cats. With increasing clinical suspicion, availability of
      abdominal ultrasonography, and introduction of pancreas-specific blood tests of
      increasing utility, it is now accepted that acute pancreatitis is probably almost
      as common in cats as it is in dogs, although the etiology(s) remain more obscure.
      Pancreatitis in cats often co-exists with inflammatory bowel disease, less
      commonly with cholangitis, and sometimes with both. Additionally, pancreatitis
      may trigger hepatic lipidosis, while other diseases, such as diabetes mellitus,
      may be complicated by pancreatitis. Therapy is similar to that used in dogs, with
      added emphasis on early nutritional support to prevent hepatic lipidosis. Less is
      known about chronic pancreatitis than the acute form, but chronic pancreatitis is
      more common in cats than it is in dogs and may respond positively to treatment
      with corticosteroids.

PMID- 23148857
TI  - Adsorption behaviors of cationic surfactants and wettability in
      polytetrafluoroethylene-solution-air systems.
AB  - Measurements of the advancing contact angle (theta) and adsorption properties
      were carried out for aqueous solutions of four cationic surfactants, hexadecanol
      glycidyl ether ammonium chloride (C(16)PC), Guerbet alcohol hexadecyl glycidyl
      ether ammonium chloride (C(16)GPC), hexadecanol polyoxyethylene(3) glycidyl ether
      ammonium chloride(C(16)(EO)(3)PC), and Guerbet alcohol hexadecyl
      polyoxyethylene(3) glycidyl ether ammonium chloride (C(16)G(EO)(3)PC), on the
      polytetrafluoroethylene (PTFE) surface using the sessile drop analysis. The
      obtained results indicate that the contact angle decreases to a minimum with the
      increasing concentration for all cationic surfactants. Surfactants with branched
      chain show lower theta values. Moreover, an increase of adhensional tension on
      the PTFE-water interface has been observed for the four cationic surfactants, and
      the branched ones have larger increases of adhensional tension. It is very
      interesting that the sharp decrease of theta appears mainly after critical
      micelle concentration (cmc) for C(16)GPC, C(16)(EO)(3)PC, and C(16)G(EO)(3)PC,
      which is quite different from traditional cationic surfactants reported in the
      literature. Especially for C(16)G(EO)(3)PC, there are two saturated adsorption
      stages on PTFE surface after cmc (which means the saturated adsorption film at
      air-solution interface has been formed). In the first saturated stage, the
      C(16)G(EO)(3)PC molecules are oriented parallel to the PTFE surface with
      saturated monolayer formed through hydrophobic interaction and hydrogen bond. In
      the second saturated stage, the hemimicelle has been formed on the PTFE surface,
      which can be supported by the QCM-D and SPR measurements.

PMID- 23148856
TI  - Chronic mild stress increases alcohol intake in mice with low dopamine D2
      receptor levels.
AB  - Alcohol use disorders emerge from a complex interaction between environmental and
      genetic factors. Stress and dopamine D2 receptor levels (DRD2) have been shown to
      play a central role in alcoholism. To better understand the interactions between
      DRD2 and stress in ethanol intake behavior, we subjected Drd2 wild-type (+/+),
      heterozygous (+/-), and knockout (-/-) mice to 4 weeks of chronic mild stress
      (CMS) and to an ethanol two-bottle choice during CMS weeks 2-4. Prior to and at
      the end of the experiment, the animals were tested in the forced swim and open
      field tests. We measured ethanol intake and preference, immobility in the force
      swim test, and activity in the open field. We show that under no CMS, Drd2+/- and
      Drd2-/- mice had lower ethanol intake and preference compared with Drd2+/+.
      Exposure to CMS decreased ethanol intake and preference in Drd2+/+ and increased
      them in Drd2+/- and Drd2-/- mice. At baseline, Drd2+/- and Drd2-/- mice had
      significantly lower activity in the open field than Drd2+/+, whereas no genotype
      differences were observed in the forced swim test. Exposure to CMS increased
      immobility during the forced swim test in Drd2+/- mice, but not in Drd2+/+ or
      Drd2-/- mice, and ethanol intake reversed this behavior. No changes were observed
      in open field test measures. These findings suggest that in the presence of a
      stressful environment, low DRD2 levels are associated with increased ethanol
      intake and preference and that under this condition, increased ethanol
      consumption could be used as a strategy to alleviate negative mood.

PMID- 23148858
TI  - [Familial colloid cyst of the third ventricle: case report and review of the
      literature].
AB  - Colloid cysts of the third ventricle are rare benign lesions. We report here an
      exceptional familial case defined by the evidence of two colloid cysts in two
      relatives of the first degree, a mother and her daughter in our description. Only
      15 cases are reported in the literature. The main differences compared with
      sporadic cases are an earlier age of discovery and a female predominance. In case
      of familial colloid cyst, we have to recover a brain MRI screening of all the
      relatives of the first degree.

PMID- 23148859
TI  - [Bilateral peroneal neuropathy following bariatric surgery].
AB  - We report the case of bilateral peroneal neuropathy following massive weight loss
      after bariatric surgery. A few months after a gastric by-pass, the patient
      developed sequentially within 6 months a L2-L3 herniated disc that required
      surgery, a severe right peroneal nerve palsy that led to decompressive surgery
      and finally contralateral peroneal nerve palsy also operated. The
      electrophysiological analysis confirmed the clinical suspicion of peroneal nerve
      compression at the fibular head. Postoperative course was favorable. Literature
      reports peroneal nerve palsy after slimming, mostly when weight loss is fast and
      marked although the issue is rarely bilateral.

PMID- 23148860
TI  - Evaluation of primary adnexal masses by 3T MRI: categorization with conventional
      MR imaging and diffusion-weighted imaging.
AB  - BACKGROUND: To investigate the 3.0-Tesla (3 T) magnetic resonance imaging (MRI)
      characteristics of primary adnexal lesions for discriminating benign from
      malignant lesions. METHODS: One hundred thirty-nine patients with pathologically
      proven primary adnexal masses referred for 3 T MRI assessment preoperatively were
      included. Baseline characteristics, components, and conventional MRI and
      diffusion-weighted imaging (DWI-MRI) signals were recorded and compared. RESULTS:
      There were 22 ovarian cysts, 33 endometriomas, 43 benign tumors and 42 malignant
      tumors. When ovarian cyst and endometrioma were excluded, there were no
      significant differences in patients' age between benign and malignant tumor (P =
      0.235). There were no significant differences (P = 0.606) in the conventional MRI
      signals and significant difference (P = 0.008) in DWI-MRI signal between the non
      malignant and malignant lesions. There was a significant difference (P = 0.000)
      in the apparent diffusion coefficient values (ADCs) between the non-malignant and
      malignant lesions. CONCLUSIONS: 3 T MRI categorized the characteristics of
      primary adnexal lesions. Conventional MRI signals were not useful for
      characterizing between benign and malignant lesions. DWI-MRI and ADCs were
      helpful for distinguishing malignant from benign ovarian lesions.

PMID- 23148861
TI  - Chiral pool based efficient synthesis of the aminocyclitol core and furanoside of
      (-)-hygromycin A: formal total synthesis of (-)-hygromycin A.
AB  - A chiral pool based synthetic strategy that leads from the readily available and
      inexpensive C(2)-symmetric tartaric acids to the chiral O
      isopropylidenebenzooxazole--a convenient precursor to the aminocyclitol core of
      hygromycin A as well as the chiral gamma-disilyloxybutyrolactone--a pivotal
      intermediate to approach to the furanoside of hygromycin A.

PMID- 23148862
TI  - The use of systems and organizational theories in the interprofessional field:
      findings from a scoping review.
AB  - Authors have commented on the limited use of theory in the interprofessional
      field and its critical importance to advancing the work in this field. While
      social psychological and educational theories in the interprofessional field are
      increasingly popular, the contribution of organizational and systems theories is
      less well understood. This paper presents a subset of the findings (those focused
      on organizational/systems approaches) from a broader scoping review of theories
      in the organizational and educational literature aimed to guide interprofessional
      education and practice. A detailed search strategy was used to identify relevant
      theories. In total, we found 17 organizational and systems theories. Nine of the
      theories had been previously employed in the interprofessional field and eight
      had potential to do so. These theories focus on interactions between different
      components of organizations which can impact collaboration and practice change.
      Given the primarily educational focus of the current research, this paper offers
      new insight into theories to support the design and implementation of
      interprofessional education and practice within health care environments. The use
      of these theories would strengthen the growing evidence base for both
      interprofessional education and practice--a common need for its varied
      stakeholders.

PMID- 23148863
TI  - Theories, relationships and interprofessionalism: learning to weave.
AB  - In this article, we illustrate the application of a number of theoretical
      frameworks we have used to guide our work in interprofessional education (IPE)
      and collaborative interprofessional care (IPC). Although we do not claim to be
      experts in any one of these theories, each has offered important insights that
      have broadened our understanding of the complexities of interprofessional
      learning and practice. We have gained an appreciation for an increasing number of
      theories relevant to IPE and IPC, and, as a result, we have woven together more
      key principles from different theories to develop activities for all levels of
      interprofessional learners and clinicians. We pay particular attention to
      relational competencies, knotworking/idea dominance, targeted tension and
      situational awareness. We are now drawing on the arts and humanities and
      complexity theory to foster relationship-building learning. Evaluation of our
      endeavors will eventually follow these latter theories for methods that better
      match the human and social experiences that underpin learning. Our "theoretical
      toolbox" therefore may be of value to educators who develop and implement
      creative interprofessional learning activities, as well as clinicians interested
      in moving toward more effective collaboration.

PMID- 23148864
TI  - The absence of endemic malaria transmission in Taiwan from 2002 to 2010: the
      implications of sustained malaria elimination in Taiwan.
AB  - The purpose of this study was to assess the epidemiology of malaria in Taiwan
      between 2002 and 2010. We analyzed data reported as part of surveillance programs
      run by the Taiwan Centers for Disease Control (Taiwan CDC). Malaria cases were
      diagnosed by blood films, polymerase chain reaction, or rapid diagnostic tests.
      The risk of re-establishment of malaria transmission in Taiwan was assessed. A
      total of 193 malaria cases were included in our analysis. All of the cases were
      associated with importation. One hundred and fifty-eight cases (82%) were
      diagnosed within 13 days from the start of symptoms/signs, and 44% of these cases
      were acquired in Africa and 42% were acquired in Asia. Plasmodium falciparum was
      responsible for the majority (49%) of these cases. Travel to an endemic area was
      associated with the acquisition of malaria. The malaria importation rate was 2.77
      per 1,000,000 travelers (range, 1.35-5.74). The reproductive number under control
      (R(c)) was 0. No endemic transmission of malaria in Taiwan was identified. This
      study suggests that maintaining a vigilant surveillance system, environmental
      management, vector-control efforts, and case management are needed to prevent
      outbreaks and sustain the eradication of malaria in Taiwan.

PMID- 23148865
TI  - Systematic study of the effects of stimulus parameters and stimulus location on
      afterdischarges elicited by electrical stimulation in the rat.
AB  - Electrical brain stimulation is used in a variety of clinical situations,
      including cortical mapping for epilepsy surgery, cortical stimulation therapy to
      terminate seizure activity in the cortex, and in deep brain stimulation therapy.
      However, the effects of stimulus parameters are not fully understood. In this
      study, we systematically tested the impact of various stimulation parameters on
      the generation of motor symptoms and afterdischarges (ADs). Focal electrical
      stimulation was delivered at subdural cortical, intracortical, and hippocampal
      sites in a rat model. The effects of stimulus parameter on the generation of
      motor symptoms and on the occurrence of ADs were examined. The effect of stimulus
      irregularity was tested using random or regular 50Hz stimulation through subdural
      electrodes. Hippocampal stimulation produced ADs at lower thresholds than
      neocortical stimulation. Hippocampal stimulation also produced significantly
      longer ADs. Both in hippocampal and cortical stimulation, when the total current
      was kept constant with changing pulse width, the threshold for motor symptom or
      AD was lowest between 50 and 100Hz and higher at both low and high frequencies.
      However, if the pulse width was fixed, the threshold did not increase above 100Hz
      and it apparently continued to decrease through 800Hz even if the difference did
      not reach statistical significance. There was no significant difference between
      random and regular stimulation. Overall, these results indicate that electrode
      location and several stimulus parameters including frequency, pulse width, and
      total electricity are important in electrical stimulation to produce motor
      symptoms and ADs.

PMID- 23148866
TI  - Voices below the surface: is there a role for the thalamus in language?

PMID- 23148867
TI  - The influence of excitatory and inhibitory landmarks on choice in environments
      with a distinctive shape.
AB  - In two experiments rats were trained to find one of two submerged platforms that
      were located in diagonally opposite corners-the correct corners-of a rectangular
      pool. Additional training was given to endow two different landmarks with
      excitatory and inhibitory properties, by using them to indicate where a platform
      was or was not located in either a rectangular (Experiment 1) or a square pool
      (Experiment 2). Subsequent test trials, with the platforms removed from the pool,
      revealed that placing the excitatory landmark in each of the four corners of the
      rectangle resulted in more time being spent in the correct corners than when the
      four corners contained inhibitory landmarks. This result is contrary to
      predictions derived from a choice rule for spatial behavior proposed by Miller
      and Shettleworth (2007).

PMID- 23148868
TI  - Contextual control of attentional allocation in human discrimination learning.
AB  - In 3 human predictive learning experiments, we investigated whether the
      allocation of attention can come under the control of contextual stimuli. In each
      experiment, participants initially received a conditional discrimination for
      which one set of cues was trained as relevant in Context 1 and irrelevant in
      Context 2, and another set was relevant in Context 2 and irrelevant in Context 1.
      For Experiments 1 and 2, we observed that a second discrimination based on cues
      that had previously been trained as relevant in Context 1 during the conditional
      discrimination was acquired more rapidly in Context 1 than in Context 2.
      Experiment 3 revealed a similar outcome when new stimuli from the original
      dimensions were used in the test stage. Our results support the view that the
      associability of a stimulus can be controlled by the stimuli that accompany it.

PMID- 23148869
TI  - [Time course of digital pressure during dialysis sessions in chronic hemodialysis
      patients. Prospective observational study of 49 patients].
AB  - OBJECTIVES: To describe and compare the evolution of digital pressure on both
      hands during a dialysis session in patients without digital ischemia, and to
      identify the parameters influencing the digital pressure. MATERIALS: Patients
      with an upper limb vascular access were prospectively included. Digital systolic
      pressure on the third finger of both hands measured by photoplethysmography and
      brachial systolic pressure were recorded before dialysis (H0) and every hour
      (from H1 to H4). RESULTS: Among 53 patients, 49 were included (exclusions: one
      surgery for ischemia, one hand tremor, two no consent). None of them had digital
      ischemia. Digital pressure homolateral to the vascular access was significantly
      lower compared with controlateral side before and during dialysis. Digital
      pressure significantly decreased on both sides during dialysis. Brachial pressure
      decreased significantly compared to H0. Only the brachial pressure decrease was
      correlated with the decrease of digital pressure. The digital pressure was less
      than 30 mmHg in six patients. No evidence of digital ischemia was reported after
      a 6-month follow-up. CONCLUSION: To our knowledge, this is the first study
      showing a significant decrease of digital pressure in both hands during
      hemodialysis in patients without digital ischemia. Further studies are necessary
      to investigate which parameters can affect digital pressure and to look for
      clinical consequence of this measurement.

PMID- 23148870
TI  - Plasmid DNA immunization with Trypanosoma cruzi genes induces cardiac and
      clinical protection against Chagas disease in the canine model.
AB  - The only existing preventive measure against American trypanosomosis, or Chagas
      disease, is the control of the transmitting insect, which has only been effective
      in a few South American regions. Currently, there is no vaccine available to
      prevent this disease. Here, we present the clinical and cardiac levels of
      protection induced by expression to Trypanosoma cruzi genes encoding the TcSP and
      TcSSP4 proteins in the canine model. Physical examination, diagnostic chagasic
      serology, and serial electrocardiograms were performed before and after
      immunization, as well as after experimental infection. We found that immunization
      with recombinant plasmids prevented hyperthermia in the acute phase of
      experimental infection and produced lymphadenomegaly as an immunological response
      against the parasite and additionally prevented heart rate elevation
      (tachycardia) in the acute and/or chronic stages of infection. Immunization with
      T. cruzi genes encoding the TcSP and TcSSP4 antigens diminished the quality and
      quantity of the electrocardiographic abnormalities, thereby avoiding progression
      to more severe developments such as right bundle branch block or ventricular
      premature complexes in a greater number of dogs.

PMID- 23148871
TI  - Immune factors and fatty acid composition in human milk from river/lake, coastal
      and inland regions of China.
AB  - Breast milk fatty acid composition may be affected by the maternal diet during
      gestation and lactation. The influence of dietary and breastmilk fatty acids on
      breast milk immune factors is poorly defined. We determined the fatty acid
      composition and immune factor concentrations of breast milk from women residing
      in river/lake, coastal and inland regions of China, which differ in their
      consumption of lean fish and oily fish. Breast milk samples were collected on
      days 3-5 (colostrum), 14 and 28 post-partum (PP) and analysed for soluble CD14
      (sCD14), transforming growth factor (TGF)-b1, TGF-b2, secretory IgA (sIgA) and
      fatty acids. The fatty acid composition of breast milk differed between the
      regions and with time PP. The concentrations of all four immune factors in breast
      milk decreased over time, with sCD14, sIgA and TGF-b1 being highest in the
      colostrum in the river and lake region. Breast milk DHA and arachidonic acid (AA)
      were positively associated, and g-linolenic acid and EPA negatively associated,
      with the concentrations of each of the four immune factors. In conclusion, breast
      milk fatty acids and immune factors differ between the regions in China
      characterised by different patterns of fish consumption and change during the
      course of lactation. A higher breast milk DHA and AA concentration is associated
      with higher concentrations of immune factors in breast milk, suggesting a role
      for these fatty acids in promoting gastrointestinal and immune maturation of the
      infant.

PMID- 23148872
TI  - Suicide and psychiatrist's liability in Italian law cases.
AB  - The aim of the study is to analyze the factors that are most frequently
      associated with a verdict of guilty delivered to the psychiatrist in cases of a
      patient's suicide in Italian law. Twenty-six sentences (1975-2009) were analyzed
      according to the claim of malpractice, patient characteristics, circumstances of
      the suicide, and reasons for the court's judgment. The court held the
      psychiatrist guilty in 12 cases, considering that the act of suicide was
      predictable and could have been avoided. Predictability was mainly related to
      errors in surveillance (7 cases), therapy (1 case), or both (2 cases). An error
      in diagnosis was considered to be related to the patient's death in two cases.
      Analysis of medical behavior considered to be erroneous and associated with a
      verdict of guilty provides an opportunity to discuss the topics relevant not only
      to practicing psychiatrists but also to experts assessing medical liability in
      cases of patient suicide. 

PMID- 23148874
TI  - Religiousness/spirituality, cardiovascular disease, and cancer: cultural
      integration for health research and intervention.
AB  - OBJECTIVE: Recently, behavioral scientists have developed greater interest in
      understanding the relations between religiousness and spirituality (R/S) and
      health. Our objectives were to (a) provide an overview of the R/S and health
      literature specific to cardiovascular disease (CVD) and cancer, (b) discuss the
      importance of religious culture considerations to behavioral medicine research,
      (c) suggest methodological changes to advance this research toward greater depth
      of understanding, and (d) begin discussion on clinically appropriate ways to
      integrate R/S into treatment. METHOD: Individual studies and meta-analyses on the
      relations of R/S with CVD and cancer were reviewed along with articles on the
      importance of culture to understanding R/S phenomena. RESULTS: Trends in the
      literature suggest that R/S predicts reductions in all-cause and CVD-related but
      not cancer mortality. R/S also shows relations with cardiovascular morbidity, and
      various dimensions of R/S show relations with cancer risk factors and well-being
      in cancer patients. Investigators have progressively studied more specific
      dimensions of R/S but have largely failed to consider them within religious
      cultural contexts. This context is essential for a deeper understanding of R/S
      and health relations and has profound methodological implications for future
      studies. CONCLUSIONS: R/S and health research is expanding; yet, the field needs
      more programmatic research and greater theoretical organization. We propose that
      consideration of R/S variables within their religious culture will provide
      structure for greater integrative understanding to move the field forward. This
      understanding is imperative if R/S is to be appropriately integrated into
      culturally sensitive clinical interventions.

PMID- 23148875
TI  - Longitudinal study of Salmonella shedding in naturally infected finishing pigs.
AB  - A 3-year longitudinal study was conducted on a multi-site farrow-to-finish
      production system. For each of 18 cohorts at three finishing sites, 50 pigs were
      randomly selected. Faecal samples were collected every 2 weeks for 16 weeks.
      Salmonella was cultured from 453 (6.6%) of 6836 faecal samples. The pig-level
      incidence of Salmonella was 20.8% (187/899 pigs). Salmonella prevalence varied
      between cohorts and within pigs. The adjusted Salmonella prevalence decreased
      over the finishing period from 6.4% to 0.8%. Intermittent detection of Salmonella
      was found in more than 50% of pigs that were positive at more than one
      collection. The finding that the majority of pigs shed intermittently has
      implications for surveillance and research study design when determining
      Salmonella status. The variability in shedding over time, as well as between and
      within cohorts and pigs suggests that there may be time-variant risk factors for
      Salmonella shedding in swine.

PMID- 23148876
TI  - Visceral adipose tissue quantification using Lunar Prodigy.
AB  - A dual-energy X-ray absorptiometry (DXA) application to measure visceral adipose
      tissue (VAT) in the android region of a total body DXA scan has recently been
      developed. This new application, CoreScan, has been validated on the Lunar iDXA
      (GE Healthcare, Madison, WI) densitometer against volumetric computed tomography.
      The geometric assumptions underlying the CoreScan model are the same on the
      Prodigy (GE Healthcare, Madison, WI) densitometer. However, differences between
      the peak X-ray voltage and detector array configurations may lead to differences
      in VAT quantification. The purpose of this study was to evaluate the agreement of
      Prodigy and iDXA CoreScan values and to characterize differences in VAT precision
      between the instruments. Data from volunteers with paired Prodigy and iDXA
      measurements were used to define empirical adjustments to the VAT algorithm
      parameters (n=59) and validate performance on Prodigy (n=62). Prodigy VAT
      measurements were highly correlated to iDXA (r=0.984). The mean of the Prodigy
      iDXA VAT volume differences was -13.8cm3 with a 95% confidence interval of -45 to
      +17cm3. The Bland-Altman 95% limits of agreement for the 2 methods were -252 to
      +224cm3. Measurement of short-term precision showed that measurement error
      variance on iDXA was smaller (p<0.01) than Prodigy (coefficient of variance: 7.3%
      vs 9.8%). Precision results are in agreement with previous reports on the
      differences between Prodigy and iDXA for body composition measures. Prodigy and
      iDXA measures of VAT are similar, but the lower precision of the Prodigy may
      require investigators to target larger changes in VAT.

PMID- 23148877
TI  - The revised EMA guideline for the investigation of bioequivalence for immediate
      release oral formulations with systemic action.
AB  - On August 1, 2010, a revised guidance regarding bioequivalence (BE) assessment
      for the approval of innovator (bridging studies, variations, line extensions) and
      generic medicinal products in the EU came into effect (EMA Guideline on the
      Investigation of Bioequivalence, CPMP/EWP/QWP/1401/98 Rev. 1/Corr**, London, 20
      January 2010). This guideline specifies the requirements for BE assessment for
      immediate release oral dosage forms with systemic action. Compared to the
      previous BE guideline of the EMA, clearer guidance is now given on several topics
      including BE assessment of highly variable drugs/drug products (HVDs/HVDPs), the
      use of metabolite data, acceptance criteria for narrow therapeutic index drugs
      (NTIDs), BCS-based biowaivers, and dose strength to be used in case of
      application for marketing authorization of several strengths. However, the health
      authorities of the various EU member states do not necessarily apply the same
      rules as far as substitution and switchability between medicinal products are
      concerned. Moreover, differences still exist between the BE guidelines of the
      major health authorities (FDA, EMA, NIHC, ...) on topics such as HVDs/HVDPs,
      NTIDs and BCS-based biowaivers. Global harmonization should be the next logical
      step to guarantee accessibility to safe and efficacious drug products for
      patients in all parts of the world.

PMID- 23148878
TI  - Fresh views on DNA structure.

PMID- 23148879
TI  - Bimolecular fluorescence complementation (BiFC): a 5-year update and future
      perspectives.
AB  - Over the past decade, bimolecular fluorescence complementation (BiFC) has emerged
      as a key technique to visualize protein-protein interactions in a variety of
      model organisms. The BiFC assay is based on reconstitution of an intact
      fluorescent protein when two complementary non-fluorescent fragments are brought
      together by a pair of interacting proteins. While the originally reported BiFC
      method has enabled the study of many protein-protein interactions, increasing
      demands to visualize protein-protein interactions under various physiological
      conditions have not only prompted a series of recent BiFC technology
      improvements, but also stimulated interest in developing completely new
      approaches. Here we review current BiFC technology, focusing on the development
      and improvement of BiFC systems, the understanding of split sites in fluorescent
      proteins, and enhancements in the signal-to-noise ratio. In addition, we provide
      perspectives on possible future improvements of the technique.

PMID- 23148880
TI  - prfectBLAST: a platform-independent portable front end for the command terminal
      BLAST+ stand-alone suite.
AB  - prfectBLAST is a multiplatform graphical user interface (GUI) for the stand-alone
      BLAST+ suite of applications. It allows researchers to do nucleotide or amino
      acid sequence similarity searches against public (or user-customized) databases
      that are locally stored. It does not require any dependencies or installation and
      can be used from a portable flash drive. prfectBLAST is implemented in Java
      version 6 (SUN) and runs on all platforms that support Java and for which
      National Center for Biotechnology Information has made available stand-alone
      BLAST executables, including MS Windows, Mac OS X, and Linux. It is free and open
      source software, made available under the GNU General Public License version 3
      (GPLv3) and can be downloaded at www.cicy.mx/sitios/jramirez or
      http://code.google.com/p/prfectblast/.

PMID- 23148881
TI  - Homogenous M13 bacteriophage quantification assay using switchable lanthanide
      fluorescence probes.
AB  - We have developed a rapid and reliable bacteriophage quantification method based
      on measurement of phage single-stranded DNA (ssDNA) using switchable lanthanide
      chelate complementation probes. One oligonucleotide probe contains a non
      fluorescent lanthanide ion carrier chelate and another probe is labeled with a
      light absorbing antenna ligand. Hybridization of the non-fluorescent
      complementation probes in adjacent positions on the released bacteriophage ssDNA
      leads to high local concentrations of the lanthanide ion carrier chelate and the
      antenna ligand, inducing formation of a fluorescent lanthanide chelate complex.
      This method enables monitoring of bacteriophage titers in a 20 min assay with a
      dynamic range of 10(9)-10(12) cfu/mL in a microtiter well format. While designed
      for titering filamentous bacteriophage used in phage display, our method also
      could be implemented in virological research as a tool to analyze ssDNA virus
      reproduction.

PMID- 23148882
TI  - HRTEM and HAADF-STEM of precipitates at peak ageing of cast A319 aluminium alloy.
AB  - High-resolution transmission electron microscopy (HRTEM) and high-angle annular
      dark-field scanning transmission electron microscopy (HAADF-STEM) were applied to
      investigate the precipitates formed during age hardening at 170+/-5 degrees C for
      up to 48h of cast A319 aluminium alloy (Al-4.93wt%Si-3.47wt%Cu). The precipitates
      at the peak-aged condition have been identified as mainly theta" together with a
      smaller amount of theta'. It is proposed that the theta" is responsible for
      hardening at peak ageing at 170 degrees C of the cast A319 aluminium alloy.

PMID- 23148873
TI  - Human conditions of insulin-like growth factor-I (IGF-I) deficiency.
AB  - Insulin-like growth factor I (IGF-I) is a polypeptide hormone produced mainly by
      the liver in response to the endocrine GH stimulus, but it is also secreted by
      multiple tissues for autocrine/paracrine purposes. IGF-I is partly responsible
      for systemic GH activities although it possesses a wide number of own properties
      (anabolic, antioxidant, anti-inflammatory and cytoprotective actions). IGF-I is a
      closely regulated hormone. Consequently, its logical therapeutical applications
      seems to be limited to restore physiological circulating levels in order to
      recover the clinical consequences of IGF-I deficiency, conditions where, despite
      continuous discrepancies, IGF-I treatment has never been related to oncogenesis.
      Currently the best characterized conditions of IGF-I deficiency are Laron
      Syndrome, in children; liver cirrhosis, in adults; aging including age-related
      cardiovascular and neurological diseases; and more recently, intrauterine growth
      restriction. The aim of this review is to summarize the increasing list of roles
      of IGF-I, both in physiological and pathological conditions, underlying that its
      potential therapeutical options seem to be limited to those proven states of
      local or systemic IGF-I deficiency as a replacement treatment, rather than
      increasing its level upper the normal range.

PMID- 23148883
TI  - Toxicological and histopathological effects of hydramethylnon on Atta sexdens
      rubropilosa (Hymenoptera: Formicidae) workers.
AB  - The leaf-cut ants are important agricultural pest, because they can cause intense
      defoliation in plants and destroy large areas cultivated. Although there are
      several works for the control of these insects by examining the toxicity of
      natural chemical compounds on various species of ants, few are focused on
      analyses of morphological changes caused in the affected organs. The aim of this
      study was to evaluate the effects of hydramethylnon on Atta sexdens rubropilosa
      workers through toxicological bioassays and morphological analysis of the post
      pharyngeal glands, midgut, and Malpighian tubules of these ants. Hydramethylnon
      dissolved either in acetone (HA) or in a mixture of acetone and soy oil (HAO) was
      added to the artificial diet at a concentration of 200MUg/mL. The workers fed
      daily with the diet containing hydramethylnon showed higher mortality than the
      controls, especially when HAO was used. Moreover, light and electron microscopy
      revealed morphological alterations in the midgut and Malpighian tubules of
      workers treated with HA, whereas alterations of the post-pharyngeal glands were
      observed in the HAO-treated group. These results indicated that the presence of
      soy oil provided an alternate route for the ingestion of the formicide's active
      ingredient and corroborated previous studies that suggested a role for the post
      pharyngeal glands in lipid metabolism. Our findings suggest that the oil may
      carry hydramethylnon to the gland lumen, resulting in lower quantity of the
      active ingredient in the intestinal lumen and Malpighian tubules that explains
      the lower degree of morphological alterations in these structures in the workers
      treated with HAO. These results may provide insight into the toxicological
      effects of hydramethylnon on leaf-cutting ants and the use of vegetable oil as an
      adjuvant in baits to control ants.

PMID- 23148885
TI  - Favourable effects of the Dietary Approaches to Stop Hypertension diet on glucose
      tolerance and lipid profiles in gestational diabetes: a randomised clinical
      trial.
AB  - Although gestational diabetes mellitus (GDM) is associated with an increased risk
      of maternal and neonatal morbidity, there is no consensus as to the optimal
      approach of nutritional management in these patients. The present study was
      designed to assess the effect of the Dietary Approaches to Stop Hypertension
      (DASH) eating plan on glucose tolerance and lipid profiles of pregnant women with
      GDM. The present randomised controlled clinical trial was performed among thirty
      four women diagnosed with GDM at 24-28 weeks of gestation. Subjects were randomly
      assigned to consume either the control diet (n 17) or the DASH eating pattern (n
      17) for 4 weeks. The control diet was designed to contain 45-55% carbohydrates,
      15-20% protein and 25-30% total fat. The macronutrient composition of the DASH
      diet was similar to the control diet; however, the DASH diet was rich in fruits,
      vegetables, whole grains and low-fat dairy products, and contained lower amounts
      of saturated fats, cholesterol and refined grains with a total of 2400 mg Na/d.
      Fasting blood samples were taken at baseline and after 4 weeks of intervention to
      measure fasting plasma glucose, glycated Hb (HbA1c) and lipid profiles.
      Participants underwent a 3 h oral glucose tolerance tests and blood samples were
      collected at 60, 120 and 180 min to measure plasma glucose levels. Adherence to
      the DASH eating pattern, compared with the control diet, resulted in improved
      glucose tolerance such that plasma glucose levels reduced at 60 (21.86 v. 20.45
      mmol/l, Pgroup = 0.02), 120 (22.3 v. 0.2 mmol/l, Pgroup = 0.001) and 180 min
      (21.7 v. 0.22 mmol/l, Pgroup = 0.002) after the glucose load. Decreased HbA1c
      levels (20.2 v. 0.05 %, Pgroup = 0.001) was also seen in the DASH group compared
      with the control group. Mean changes for serum total (20.42 v. 0.31 mmol/l,
      Pgroup = 0.01) and LDL-cholesterol (20.47 v. 0.22 mmol/l, Pgroup = 0.005), TAG
      (20.17 v. 0.34 mmol/l, Pgroup = 0.01) and total:HDL-cholesterol ratio (20.6 (SD
      0.9) v. 0.3 (SD 0.8), Pgroup = 0.008) were significantly different between the
      two diets. Additionally, consumption of the DASH diet favourably influenced
      systolic blood pressure (22.6 v. 1.7 mmHg, Pgroup = 0.001). Mean changes of
      fasting plasma glucose (20.29 v. 0.15 mmol/l, Pgroup = 0.09) were nonsignificant
      comparing the DASH diet with the control diet. In conclusion, consumption of the
      DASH eating pattern for 4 weeks among pregnant women with GDM resulted in
      beneficial effects on glucose tolerance and lipid profiles compared with the
      control diet.

PMID- 23148884
TI  - Functional role of post-translational modifications of Sp1 in tumorigenesis.
AB  - Specific protein 1 (Sp1), the first transcription factor to be isolated,
      regulates the expression of numerous genes involved in cell proliferation,
      apoptosis, and differentiation. Recent studies found that an increase in Sp1
      transcriptional activity is associated with the tumorigenesis. Moreover, post
      translational modifications of Sp1, including glycosylation, phosphorylation,
      acetylation, sumoylation, ubiquitination, and methylation, regulate Sp1
      transcriptional activity and modulate target gene expression by affecting its DNA
      binding activity, transactivation activity, or protein level. In addition, recent
      studies have investigated several compounds with anti-cancer activity that could
      inhibit Sp1 transcriptional activity. In this review, we describe the effect of
      various post-translational modifications on Sp1 transcriptional activity and
      discuss compounds that inhibit the activity of Sp1.

PMID- 23148886
TI  - The BclI polymorphism of the glucocorticoid receptor gene is associated with
      emotional memory performance in healthy individuals.
AB  - Glucocorticoids, stress hormones released from the adrenal cortex, are important
      players in the regulation of emotional memory. Specifically, in animals and in
      humans, glucocorticoids enhance memory consolidation of emotionally arousing
      experiences, but impair memory retrieval. These glucocorticoid actions are partly
      mediated by glucocorticoid receptors in the hippocampus, amygdala and prefrontal
      cortex, key brain regions for emotional memory. In a recent study in patients who
      underwent cardiac surgery, the BclI polymorphism of the glucocorticoid receptor
      gene (NR3C1) was associated with traumatic memories and posttraumatic stress
      disorder symptoms after intensive care therapy. Based on this finding, we
      investigated if the BclI polymorphism is also associated with emotional memory in
      healthy young subjects (N=841). We used a picture-learning task consisting of
      learning and recalling neutral and emotional photographs on two consecutive days.
      The BclI variant was associated with short-delay recall of emotional pictures on
      both days, with GG carriers showing increased emotional memory performance as
      compared to GC and CC carriers. We did not detect a genotype-dependent difference
      in recall performance for neutral pictures. These findings suggest that the Bcll
      polymorphism contributes to inter-individual differences in emotional memory also
      in healthy humans.

PMID- 23148888
TI  - Sex differences in smoking initiation among children and adolescents.
AB  - OBJECTIVE: To understand differences in the context of, and reasons for, smoking
      initiation among boys and girls. STUDY DESIGN: Sex- and gender-based analysis of
      published literature. METHODS: A comprehensive search of the PUBMED database was
      conducted for studies (published in the English language) between January 1980
      and October 2010 that assessed smoking initiation among children and adolescents
      (aged 8-19 years). Information on demographics and study design were extracted by
      two authors from each eligible article. A sex- and gender-based analysis was
      employed. RESULTS: Of 40 publications initially obtained, studies in adult or
      college-age populations (n = 9) and studies that did not examine the specific
      context of smoking initiation (n = 19) were excluded. Thus, this review is based
      on 12 eligible studies. Eligible studies represented data from 10,831 children
      and adolescents in nine countries. In most studies, boys had a lower age of
      smoking initiation than girls, with the exception of two studies from Yemen and
      China. In some countries, girls reported obtaining and smoking their first
      cigarette from family members at home. In most studies, the school was the main
      setting for initiation for boys, whereas the home setting was the main setting
      for girls. CONCLUSIONS: This study highlights gender and cultural differences in
      smoking initiation among children and adolescents. Smoking prevention programmes
      should thus include gender- and culture-specific content related to smoking
      initiation. Future studies may further examine gender- and culture-specific
      messaging to inform policies and enhance tailored programmes aimed at preventing
      smoking initiation.

PMID- 23148887
TI  - Pervasive alterations of emotional and neuroendocrine responses to an acute
      stressor after neonatal amygdala lesions in rhesus monkeys.
AB  - The current study examined the long-term effects of neonatal amygdala lesions on
      emotional and hypothalamic-pituitary-adrenal (HPA) axis reactivity to an acute
      stressor in rhesus monkeys. Rhesus monkeys received either bilateral MRI-guided
      ibotenic acid amygdala (Neo-Aibo; n=6) or sham (Neo-C; n=7) lesions between 7 and
      14 days of age. Emotional reactivity was assessed using the Human Intruder
      paradigm at 2 months, 4.5 months, and 6-8 years of age, whereas stress
      neuroendocrine response was only assessed in adulthood (6-8 years). The
      modulation of defensive and emotional behaviors based on the gaze direction of
      the intruder emerged between 2 and 4 months of age in surrogate-peer reared sham
      operated infant monkeys, as already shown for mother-reared infants. Although
      neonatal amygdala lesions did not impair the ability to exhibit defensive and
      emotional behaviors, it altered the modulation of these responses based on the
      intruder's gaze direction. The changes in emotional reactivity after neonatal
      amygdala lesions emerged in infancy and persisted throughout adulthood when they
      were associated with a reduction of basal cortisol levels and a blunted cortisol
      response to the stressor. These changes are reminiscent of those found after
      adult-onset amygdala lesions, demonstrating little functional compensation
      following early amygdala damage.

PMID- 23148889
TI  - Parental attitudes on expanded newborn screening in Hong Kong.
AB  - OBJECTIVES: Classical inborn errors of metabolism (IEM) affect about 1 in 4000 in
      Hong Kong. Despite the widespread implementation of expanded newborn screening in
      most countries, Hong Kong only screen for three conditions and the awareness of
      public has not been evaluated. This is the first study to examine the parental
      knowledge and attitudes towards expanded newborn screening in Hong Kong. METHODS:
      A cross-sectional survey was conducted in the Princess Margaret Hospital. Parents
      with babies born from 1st July to 31st October 2010 were randomly recruited.
      Fifteen questions relating to the knowledge of newborn screening and biochemical
      genetic disorders, preferences about the features of newborn screening, the
      economic values, and attitudes toward false positive results were asked. RESULTS:
      In total, 172 subjects were interviewed by phone (overall response rate 97.2%).
      There were 87.8% parents who had never heard of expanded newborn screening; 99.4%
      demanded more parental education; 83.5% thought the programme should be
      implemented immediately; 97.7% supported population screening, even though the
      diseases are incurable; 93.9% accepted the possibility of false positive and
      false negative results; 70.4% preferred a voluntary basis; 83.2% believed that
      the programme should be fully government funded as basic primary care; 98.8%
      agreed that Hong Kong should follow mainland China's policy on expanded newborn
      screening; 98.2% required pre-test counseling; and 96.4% required an explicit
      parental consent before blood sampling. CONCLUSIONS: The response from parents
      overwhelmingly favoured having expanded newborn screening in Hong Kong. Parental
      tolerance was high. Parents valued the parental autonomy with informed consent
      and pre-test counseling the most. The success of any screening programme requires
      the public participation and this study is the first to prove the parental call
      for an expanded newborn screening in Hong Kong.

PMID- 23148890
TI  - Construct and convergent validity and repeatability of the Questionnaire
      d'Activite Physique pour les Personnes Agees (QAPPA), a physical activity
      questionnaire for the elderly.
AB  - OBJECTIVES: To investigate repeatability, and construct and convergent validity
      of the Questionnaire d'Activite Physique pour les Personnes Agees (QAPPA), a self
      reported physical activity questionnaire for the elderly. STUDY DESIGN: Cross
      sectional and prospective (1-year follow-up) data from two postal surveys among
      members of the medical insurance scheme of the French national education system.
      METHODS: A questionnaire on general health and the QAPPA were sent out twice,
      with a 1-year interval. Participants were >=60 years of age (sample size varied
      from 225 to 393 according to the analysis). Intraclass correlations, Bland-Altman
      plots (continuous variables) and kappa coefficients (categorical variable) were
      used for repeatability analyses. Comparison tests were performed (Wilcoxon rank
      sum test and Kruskal-Wallis test) for construct validity. Chi-squared test and
      correlation coefficients were used to establish the convergent validity of the
      QAPPA. RESULTS: The QAPPA had acceptable repeatability with a 1-year interval,
      with moderate test-retest correlation coefficients (from r = 0.46 to r = 0.64)
      and a fair-to-good kappa coefficient (kappa = 0.44). It discriminated between
      individuals by age group (with younger persons being more physically active than
      older persons) and exercise behaviour (with regular exercisers being more active
      than non-exercisers). The QAPPA was negatively associated with decline in
      physical function and comorbidity, and was positively associated with self
      reported health and satisfaction with body functioning. CONCLUSION: This study
      found that the QAPPA is a valid tool for assessing the physical activity of older
      adults. It could be used for research purposes as well as for epidemiological
      surveillance.

PMID- 23148891
TI  - Thank you for not smoking: evidence from the Italian smoking ban.
AB  - By 2030, tobacco is expected to be the cause of about 10 million deaths per year
      worldwide. In Italy tobacco smoking is still a pervasive and relevant phenomenon.
      Using data from a national health survey, we investigate how individuals react to
      the introduction of a public smoking ban in Italy. Our estimates suggest that the
      Italian smoking ban in private places open to the public reduced smoking
      prevalence by 1.3% and daily cigarettes consumption by 8%. We find heterogeneous
      effects by gender, marital status, and region of residence.

PMID- 23148892
TI  - gamma-Aminobutyric acid transaminase deficiency impairs central carbon metabolism
      and leads to cell wall defects during salt stress in Arabidopsis roots.
AB  - Environmental constraints challenge cell homeostasis and thus require a tight
      regulation of metabolic activity. We have previously reported that the gamma
      aminobutyric acid (GABA) metabolism is crucial for Arabidopsis salt tolerance as
      revealed by the NaCl hypersensitivity of the GABA transaminase (GABA-T,
      At3g22200) gaba-t/pop2-1 mutant. In this study, we demonstrate that GABA-T
      deficiency during salt stress causes root and hypocotyl developmental defects and
      alterations of cell wall composition. A comparative genome-wide transcriptional
      analysis revealed that expression levels of genes involved in carbon metabolism,
      particularly sucrose and starch catabolism, were found to increase upon the loss
      of GABA-T function under salt stress conditions. Consistent with the altered
      mutant cell wall composition, a number of cell wall-related genes were also found
      differentially expressed. A targeted quantitative analysis of primary metabolites
      revealed that glutamate (GABA precursor) accumulated while succinate (the final
      product of GABA metabolism) significantly decreased in mutant roots after 1 d of
      NaCl treatment. Furthermore, sugar concentration was twofold reduced in gaba
      t/pop2-1 mutant roots compared with wild type. Together, our results provide
      strong evidence that GABA metabolism is a major route for succinate production in
      roots and identify GABA as a major player of central carbon adjustment during
      salt stress.

PMID- 23148893
TI  - Metallothionein 2a gene expression is increased in subcutaneous adipose tissue of
      type 2 diabetic patients.
AB  - STUDY BACKGROUND: Insulin resistance plays an important role in the pathogenesis
      of type 2 diabetes and the metabolic syndrome. Many of the genes and pathways
      involved have been identified but some remain to be defined. Metallothioneins
      (Mts) are a family of anti-oxidant proteins and metallothionein 2a (Mt2a)
      polymorphims have been recently associated with type 2 diabetes and related
      complications. Our objective was to determine the Mt2a gene expression levels in
      adipose tissues from diabetic patients and the effect of Mt treatment on
      adipocyte insulin sensitivity. METHODS: Samples of subcutaneous and visceral
      adipose tissues from lean, type 2 diabetic and non-diabetic obese patients were
      analysed using RT-qPCR for Mt2a mRNA abundance. The regulation of Mt2a expression
      was further studied in 3T3-L1 adipocytes treated or not with TNFalpha (10 ng/ml,
      72 h) to induce insulin resistance. The effects of Mt on glucose uptake were
      investigated in cultured adipocytes treated with recombinant Mt protein. RESULTS:
      We found that the Mt2a gene expression was significantly higher in adipose tissue
      of type 2 diabetic patients in comparison to that of lean (p=0.003) subjects. In
      3T3-L1 adipocytes, insulin resistance induced by TNFalpha increased Mt2a mRNA
      levels (p=3*10(-4)) and insulin-stimulated glucose uptake was significantly
      inhibited by 53% (p=8*10(-4)) compared to vehicle, when 3T3-L1 adipocytes were
      treated with Mt protein. CONCLUSIONS: These data suggest that Mt2a might be
      involved in insulin resistance through the up-regulation of Mt gene expression,
      which may lead to the modulation of insulin action in fat cells. These results
      suggest the concept of considering Mt proteins as markers and potential targets
      in type 2 diabetes.

PMID- 23148894
TI  - A systematic review of in vitro studies conducted on effect of herbal products on
      secretion of insulin from Langerhans islets.
AB  - PURPOSE: Diabetes mellitus is the most important health problem that its
      prevalence is increasing. Diabetes is characterized by defects in insulin
      secretion, insulin action or both. Recent studies provided evidences that loss of
      functional beta-cell mass through apoptosis is central to the development of
      diabetes. The management of diabetes without any side effects is still a
      challenge to the medical system. Recently, there has been a special interest to
      herbal medicine in care and management of diabetes due to their natural origin
      and less side effects. The current systematic review focuses on main component of
      antidiabetic plants with directly effect on insulin secretion of pancreas.
      METHODS: All in vitro studies which assessed the potential effect of, main
      components, multi herbal, whole plant, or extract of the plants directly on
      pancreatic insulin secretion published from 2001 to November 2011 were included.
      Exclusion criteria were clinical trial studies that did not assess insulin
      secretion, and review articles, or letters to the editor. RESULTS: The majority
      of these studies showed that the improvement of beta-cell function and insulin
      secretion is possible with antioxidant compounds. Suppression of oxidative
      stress, cytokine-induced impairment, suppression of nuclear factor kappaB a key
      regulator of endothelial activation, activation of uncoupling protein 2 (UCP2),
      insulin-like activity and increasing intracellular calcium, were among the most
      important indicated pathways. CONCLUSIONS: By considering the role of oxidative
      stress in pathogenesis of beta-cell dysfunction, antioxidant compounds could be
      helpful in management of diabetes and its complications.

PMID- 23148895
TI  - Pulmonary exposure to particles from diesel exhaust, urban dust or single-walled
      carbon nanotubes and oxidatively damaged DNA and vascular function in apoE(-/-)
      mice.
AB  - This study compared the oxidative stress level and vasomotor dysfunction after
      exposure to urban dust, diesel exhaust particles (DEP) or single-walled carbon
      nanotubes (SWCNT). DEP and SWCNT increased the production of reactive oxygen
      species (ROS) in cultured endothelial cells and acellullarly, whereas the
      exposure to urban dust did not generate ROS. The apoE(-/-) mice, which were
      exposed twice to 0.5 mg/kg of the particles by intratracheal (i.t.) instillation,
      had unaltered acetylcholine-elicited vasorelaxation in aorta segments. There was
      unaltered pulmonary expression level of Vcam-1, Icam-1, Hmox-1 and Ogg1. The
      levels of oxidatively damaged DNA were unchanged in lung tissue. The exposure to
      SWCNT significantly increased the expression of Ccl-2 in the lung tissue of the
      mice. The exposure to DEP and SWCNT was associated with elevated ROS production
      in cultured cells, whereas i.t. instillation of the same particles had no effect
      on biomarkers of pulmonary oxidative stress and dilatory dysfunction in the
      aorta.

PMID- 23148896
TI  - Neuropsychological correlates of P50 sensory gating in patients with
      schizophrenia.
AB  - Impaired inhibition of P50 cerebral evoked response is one of the best validated
      endophenotypes in schizophrenia. There are controversial data on the relationship
      between P50 evoked potential deficit and measures of cognitive function in
      schizophrenia. A comprehensive clinical and neurocognitive assessment plus an
      evaluation of P50 sensory gating was performed in 160 schizophrenia patients and
      64 controls. Neurocognitive scores from each cognitive domain were converted to
      demographically-adjusted T-scores (age, gender, and years of education) for all
      study participants. The relationship between P50 and neurocognitive variables was
      assessed via parametric and nonparametric correlations and categorical
      strategies: we compared neuropsychological test scores in patients and controls
      in the lowest P50 quartile vs. the highest. Controls had better performance than
      schizophrenia patients in all cognitive domains. Schizophrenia patients had
      significantly higher P50 ratios than controls, and no significant correlation was
      found between P50 gating measures and neuropsychological test scores in
      schizophrenia patients or healthy controls. Moreover, no differences in
      neurocognitive performance were found between subjects in the lowest P50 ratio
      quartile vs. the highest in healthy controls or patients with schizophrenia. We
      concluded that there is no evidence of an association between P50 ratio and
      cognitive measures in schizophrenia patients, and this seems to be also the case
      in healthy controls.

PMID- 23148897
TI  - Validated five-factor model of positive and negative syndrome scale for
      schizophrenia in Chinese population.
AB  - The Positive and Negative Syndrome Scale (PANSS) is the most widely used
      instrument to assess the severity of symptoms of schizophrenia. Most studies have
      showed that PANSS measures five dimensions of symptomatology of schizophrenia.
      However, few studies have ever investigated the structure of PANSS in Chinese
      schizophrenia population. We recruited two large independent study samples
      including 903 and 942 Chinese schizophrenia patients and examined the underlying
      structure of PANSS. By building a confirmatory factor analysis (CFA) model based
      on the factor loadings of the exploratory factor analysis (EFA) and by testing
      the CFA model in an independent validation sample, we found that PANSS scores
      consisted of five factors, which were positive factor, negative factor,
      excitement factor, depression factor, and cognitive factor. The items loaded on
      these factors were similar to the consensus items published in previous studies
      except for PANSS items P2 conceptual disorganization, P5 grandiosity, N5 abstract
      thinking, and G11 poor attention. This difference might be due to the influence
      of culture on clinical presentation of schizophrenia. By elucidating the
      structure, symptoms of Chinese schizophrenia patients could possibly be
      deconstructed and investigated in future studies.

PMID- 23148899
TI  - A test of the domain-specific acculturation strategy hypothesis.
AB  - Acculturation literature has evolved over the past several decades and has
      highlighted the dynamic ways in which individuals negotiate experiences in
      multiple cultural contexts. The present study extends this literature by testing
      M. J. Miller and R. H. Lim's (2010) domain-specific acculturation strategy
      hypothesis-that individuals might use different acculturation strategies (i.e.,
      assimilated, bicultural, separated, and marginalized strategies; J. W. Berry,
      2003) across behavioral and values domains-in 3 independent cluster analyses with
      Asian American participants. Present findings supported the domain-specific
      acculturation strategy hypothesis as 67% to 72% of participants from 3
      independent samples using different strategies across behavioral and values
      domains. Consistent with theory, a number of acculturation strategy cluster group
      differences emerged across generational status, acculturative stress, mental
      health symptoms, and attitudes toward seeking professional psychological help.
      Study limitations and future directions for research are discussed.

PMID- 23148898
TI  - White matter organization and neurocognitive performance variability in
      schizophrenia.
AB  - BACKGROUND: White matter alterations in schizophrenia are associated with
      deficits in neurocognitive performance. Recently, across task within-individual
      variability (WIV) has emerged as a useful construct for assessing the profile in
      cognitive performance in schizophrenia. However, the neural basis of WIV has not
      been studied in patients with schizophrenia. METHODS: Twenty-five patients with
      schizophrenia (SZ) and 27 healthy comparison subjects (HC) performed a
      computerized neurocognitive battery (CNB) and underwent diffusion tensor imaging
      (DTI). WIV for performance accuracy and speed on the CNB was calculated across
      tasks. Voxel-wise group comparisons of white matter fractional anisotropy (FA)
      were performed using tract-based spatial statistics (TBSS). The relationship
      between accuracy and speed WIV on the CNB and white matter FA was examined within
      the regions that differentiated patients and healthy comparison subjects.
      RESULTS: SZ had higher WIV for performance accuracy and speed as compared to HC.
      FA in SZ compared to HC was reduced in bilateral frontal, temporal and occipital
      white matter including a large portion of the corpus callosum. In white matter
      regions that differed between patients and comparison subjects, higher FA in the
      left cingulum bundle and left fronto-occipital fasciculus were associated with
      lower CNB speed WIV for HC, but not SZ. Accuracy WIV was not associated with
      differences in white matter FA between SZ and HC. CONCLUSIONS: We provide
      evidence that WIV is greater in patients with SZ and that this greater within
      individual variability in performance in patients is associated with disruptions
      of WM integrity in specific brain regions.

PMID- 23148900
TI  - Converging identities: dimensions of acculturation and personal identity status
      among immigrant college students.
AB  - The present study was designed to ascertain the extent to which dimensions of
      acculturation would differ across personal identity statuses in a sample of 2,411
      first- and second-generation, immigrant, college-attending emerging adults.
      Participants from 30 colleges and universities around the United States completed
      measures of personal identity processes, as well as of heritage and American
      cultural practices, values, and identifications. Cluster-analytic procedures were
      used to classify participants into personal identity statuses based on the
      personal identity processes. Results indicated that, across ethnic groups,
      individuals in the achieved and searching moratorium statuses reported the
      greatest endorsement of heritage and American cultural practices, values, and
      identifications; and individuals in the carefree diffusion status reported the
      lowest endorsement of all the cultural variables under study. These results are
      discussed in terms of the convergence between personal identity and cultural
      identity processes.

PMID- 23148901
TI  - Race and gender discrimination in the Marines.
AB  - Although women of color have been hypothesized to experience double jeopardy in
      the form of chronic exposure to both race-based (RBD) and gender-based
      discrimination (GBD; Beal, 1970), few empirical investigations that examine both
      RBD and GBD in multiple comparison groups have been conducted. In addition to
      being one of the only simultaneous examinations of RBD and GBD in multiple
      comparison groups, the current study includes both self-report and objective
      behavioral data to examine the independent and interactive effects of both forms
      of discrimination. This study is also the first of its kind to examine these
      constructs in these ways and to explore their impact in a unique sample of
      ethnically diverse male and female Marine recruits (N = 1,516). As anticipated,
      both RBD and GBD had a strong and consistent negative impact on mental health
      symptoms (e.g., depression, anxiety), independent of the contributions of gender
      and race. Partial support was found for the hypothesis that people of color are
      able to maintain resiliency (as measured by physical fitness testing) in the face
      of low levels of RBD, but are less able to overcome the negative effects of
      discrimination at high levels. It is interesting to note that the interaction
      between race, gender, and levels of discrimination was only found with objective
      physical fitness test scores but not with self-report measures. These findings
      underscore the importance of including objective measures when assessing the
      impact of discrimination in order to understand these complex interrelationships.

PMID- 23148902
TI  - The effect of immigration and acculturation on victimization among a national
      sample of Latino women.
AB  - The current study examined the effect of immigrant status, acculturation, and the
      interaction of acculturation and immigrant status on self-reported victimization
      in the United States among Latino women, including physical assault, sexual
      assault, stalking, and threatened violence. In addition, immigrant status,
      acculturation, gender role ideology, and religious intensity were examined as
      predictors of the count of victimization among the victimized subsample. The
      Sexual Assault Among Latinas (SALAS) Study surveyed 2,000 adult Latino women who
      lived in high-density Latino neighborhoods in 2008. The present study reports
      findings for a subsample of women who were victimized in the United States (n =
      568). Immigrant women reported significantly less victimization than U.S.-born
      Latino women in bivariate analyses. Multivariate models showed that Anglo
      orientation was associated with greater odds of all forms of victimization,
      whereas both Latino orientation and being an immigrant were associated with lower
      odds of all forms of victimization. Latino orientation was more protective for
      immigrant women than for U.S.-born Latino women with regard to sexual
      victimization. Among the victimized subsample, being an immigrant, Anglo
      acculturation, and masculine gender role were associated with a higher
      victimization count, whereas Latino orientation and religious intensity were
      associated with a lower victimization count. The findings point to the risk
      associated with being a U.S. minority, the protective value of Latino cultural
      maintenance, and the need for services to reach out to Anglo acculturated Latino
      women.

PMID- 23148903
TI  - Attitudes toward unauthorized immigrants, authorized immigrants, and refugees.
AB  - Rates of human migration are steadily rising and have resulted in significant
      sociopolitical debates over how to best respond to increasing cultural diversity
      and changing migration patterns. Research on prejudicial attitudes toward
      immigrants has focused on the attitudes and beliefs that individuals in the
      receiving country hold about immigrants. The current study enhances this
      literature by examining how young adults view authorized and unauthorized
      immigrants and refugees. Using a between-groups design of 191 undergraduates, we
      found that participants consistently reported more prejudicial attitudes, greater
      perceived realistic threats, and greater intergroup anxiety when responding to
      questions about unauthorized compared with authorized immigrants. Additionally,
      there were differences in attitudes depending on participants' generational
      status, with older-generation participants reporting greater perceived realistic
      and symbolic threat, prejudice, and anxiety than newer-generation students. In
      some instances, these effects were moderated by participant race/ethnicity and
      whether they were evaluating authorized or unauthorized immigrants. Lastly,
      perceived realistic threat, symbolic threat, and intergroup anxiety were
      significant predictors of prejudicial attitudes. Overall, participants reported
      positive attitudes toward refugees and resettlement programs in the United
      States. These findings have implications for future research and interventions
      focused on immigration and prejudice toward migrant groups.

PMID- 23148904
TI  - The benefits of discussing suicide with Alaska native college students:
      qualitative analysis of in-depth interviews.
AB  - Suicide represents a significant health disparity for communities in rural
      Alaska, and has implications for mental health among people who have lost loved
      ones from suicide. A qualitative interview study was conducted to examine the
      ways in which suicide has affected the lives of college students who have
      migrated from rural villages to an urban university (N = 25). The present
      research represents a secondary aim of the study-specifically, we examined the
      affective responses of Alaska Native college students from rural villages after
      completing in-depth semistructured interviews about their experiences related to
      suicide. Debriefing questions posed at the conclusion of the interviews revealed
      that the majority of participants (n 16) stated they felt "better" after
      completing the interview, and no participants reported feeling "worse." No
      participant required the use of the safety plan developed in case of severe
      emotional distress. All participants indicated they would be interested in
      participating in future research. Analysis of questions pertaining to the
      interview experience revealed the salience of foundation (the participant's prior
      experience discussing issues like suicide), process (the interview questions and
      questioning style), and outcomes (the challenges and benefits of participation
      described by the respondent). Findings provided important insights concerning the
      experience of discussing past trauma, perceived importance of research addressing
      coping with suicide, and the influence of past experiences in the process of
      talking about suicide.

PMID- 23148905
TI  - Recognizing uncertainty increases robustness and reproducibility of mass
      spectrometry-based protein inferences.
AB  - Parsimony and protein grouping are widely employed to enforce economy in the
      number of identified proteins, with the goal of increasing the quality and
      reliability of protein identifications; however, in a counterintuitive manner,
      parsimony and protein grouping may actually decrease the reproducibility and
      interpretability of protein identifications. We present a simple illustration
      demonstrating ways in which parsimony and protein grouping may lower the
      reproducibility or interpretability of results. We then provide an example of a
      data set where a probabilistic method increases the reproducibility and
      interpretability of identifications made on replicate analyses of Human Du145
      prostate cancer cell lines.

PMID- 23148906
TI  - The contribution of low serum testosterone levels to mortality in men.

PMID- 23148910
TI  - Epidemiology and aetiology of encephalitis in Canada, 1994-2008: a case for
      undiagnosed arboviral agents?
AB  - Encephalitis is a clinical syndrome often associated with infectious agents. This
      study describes the epidemiology and disease burden associated with encephalitis
      in Canada and explores possible associations with arboviral causes. Encephalitis
      associated hospitalizations, 1994-2008, were analysed according to aetiological
      category (based on ICD-9/ICD-10 codes) and other factors using multivariate
      logistic regression for grouped (blocked) data and negative binomial regression.
      A discrete Poisson model tested spatio-temporal clustering of hospitalizations
      associated with unclassified and arboviral encephalitis aetiologies. Encephalitis
      accounted for an estimated 24028 hospitalizations in Canada (5.2/100 000
      population) and unknown aetiologies represented 50% of these hospitalizations. In
      2003, clusters of unclassified encephalitis were identified in the summer and
      early autumn months signifying potential underlying arboviral aetiologies. Spatio
      temporal patterns in encephalitis hospitalizations may help us to better
      understand the disease burden associated with arboviruses and other zoonotic
      pathogens in Canada and to develop appropriate surveillance systems.

PMID- 23148911
TI  - Control of stem cells and cancer stem cells by Hedgehog signaling: pharmacologic
      clues from pathway dissection.
AB  - Hedgehog is a key morphogen regulating embryonic development and tissue repair.
      Remarkably, when misregulated, it leads to tumorigenesis. Hedgehog signaling is
      triggered by binding of ligands with transmembrane receptor Ptch and is
      subsequently mediated by transcriptional effectors belonging to the Gli family,
      whose functions is tuned by a number of molecular interactions and post-synthetic
      modifications. The complex of these regulatory circuitries provides a tight
      control of developmental processes, mainly involving the modulation of genes
      determining the fate of stem cells. Similarly, Hedgehog regulates cancer stem
      cells fostering tumorigenesis. To this regard, these processes represent
      promising targets for novel therapeutic strategies aiming at the control of
      stemness reactivation and maintenance in cancer.

PMID- 23148912
TI  - A rare but distinctive cause of acute abdomen: appendiceal diverticulitis.
AB  - BACKGROUND: Diverticulosis and diverticulitis of appendix vermiformis is a rare
      diagnosis. Clinical and laboratory examinations do not show a difference between
      a progressing diverticulitis and simplex appendicitis. But this entity has a
      higher mortality rate than common appendicitis. OBJECTIVE: This case is presented
      to illustrate the point that preoperative simple diagnosis of acute appendicitis
      according to the clinical signs and physical examination may not only be
      insufficient, but could be fatal in certain circumstances, like appendiceal
      diverticulitis, if surgical intervention is delayed. CASE REPORT: Here we present
      a female patient with a history of right lower abdominal pain and fever of 3 days
      duration. She was diagnosed with acute appendicitis according to the preoperative
      physical, laboratory, and imaging examinations. The appendiceal diverticulitis
      accompanying acute appendicitis was an intraoperative finding, which was proven
      by histopathologic examination. CONCLUSION: It is not easy to document this
      entity preoperatively. When diagnosed either preoperatively by imaging studies or
      intraoperatively, the only choice is appendectomy to prevent its serious
      complications.

PMID- 23148913
TI  - Estrous cycle variation in anxiolytic-like effects of topiramate in Wistar rats
      in two animal models of anxiety-like behavior.
AB  - The anxiolytic-like effects of topiramate were assessed during several estrous
      cycle phases in Wistar rats tested in two animal models of anxiety-like behavior.
      In a conflict operant test, during proestrus, diazepam (1.3, 2.0mg/kg; P<0.05) or
      topiramate (20.0, 30.0mg/kg; P<0.05) increased the number of immediately punished
      responses. During metestrus-diestrus only the highest doses of diazepam
      (2.0mg/kg, P<0.05) or topiramate (30.0mg/kg, P<0.05) increased the number of
      immediately punished reinforcers. Similar results were obtained in the elevated
      plus-maze test: during proestrus, diazepam (1.3, 2.0mg/kg; P<0.05) or topiramate
      (20.0, 30.0mg/kg; P<0.05) produced anxiolytic-like actions. During metestrus
      diestrus only the highest doses of diazepam (2.0mg/kg, P<0.05) or topiramate
      (30.0mg/kg, P<0.05) produced anxiolytic-like actions. Neither diazepam nor
      topiramate nor estrous cycle phases significantly modified the number of closed
      arm entries in the elevated plus-maze test. It is concluded that the response to
      neuromodulatory drugs for anxiety-like behavior varied according to the estrous
      cycle phases.

PMID- 23148914
TI  - Genome-wide characterization of the CBF/DREB1 gene family in Brassica rapa.
AB  - The C-repeat/dehydration-responsive element binding transcription factors
      (CBF/DREBs) are important proteins in involved in responses to abiotic stress in
      plants. We identified ten BrDREB1 genes belonging to the CBF/DREB1 gene family in
      the Brassica rapa whole genome sequence, whereas six genes are found in the
      Arabidopsis thaliana genome. The deduced amino acid sequences of the B. rapa
      genes showed conserved motifs shared with other known plant CBF/DREB1s.
      Comparative analysis revealed that nine of the BrDREB1 genes were derived from
      the recent genome triplication in the tribe Brassiceae and the other one was
      translocated. The nine genes were located in seven of the 12 macrosyntenic blocks
      that are triplicated counterparts of four Arabidopsis macrosyntenic blocks
      harboring six CBF/DREB1 genes: one gene on each of three blocks and three
      tandemly arrayed genes on another block. We inspected the expression patterns of
      eight BrDREB1 genes by RT-PCR and microarray database searches. All eight genes
      were highly up-regulated during cold (4  degrees C) treatment, and some of them
      were also responsive to salt (250 mM NaCl), drought (air drying), and ABA (100
      MUM) treatment. Microarray data for plant developmental stages revealed that
      BrDREB1C2 was highly expressed during a period of cold treatment for
      vernalization, similar to abiotic stress-inducible genes homologous to Bn28a,
      Bn47, Bn115, and BoRS1, but almost opposite of BrFLC genes. Taken together, the
      number of BrDREB1 genes increased to 10 by genome triplication and
      reorganization, providing additional functions in B. rapa abiotic stress
      responses and development, as distinct from their Arabidopsis homologs.

PMID- 23148915
TI  - Validation of energy requirement references for exclusively breast-fed infants.
AB  - In paediatric practice, mean reference energy requirements for groups are often
      used to predict individual infant energy requirements. References from the
      FAO/WHO/United Nations University are based on infants not fed according to the
      current infant feeding recommendations. The objective of the present study was to
      measure total energy expenditure (TEE) and determine energy requirements using
      criterion methods, and validate the use of TEE prediction equation and mean
      energy requirement references for predicting individual TEE and energy
      requirements, respectively, in infants who were exclusively breast-fed (EBF) to 6
      months of age. EBF infants were included from Greater Glasgow for measurements at
      3.5 (n 36) and 6 (n 33) months of age. TEE was measured using doubly labelled
      water and energy requirements were determined using the factorial approach. TEE
      and energy requirements were also predicted using equations based on body weight.
      Relationships between criterion methods and predictions were assessed using
      correlations. Paired t tests and Bland-Altman plots were used to assess
      agreement. At the population level, predicted and measured TEE were similar. The
      energy requirement reference significantly underestimated energy requirements by
      7.2% at 3.5 months at the population level, but there was no bias at 6 months.
      Errors at individual levels were large and energy requirements were
      underestimated to a larger extent for infants with higher energy requirements.
      This indicates that references presently used in clinical practice to estimate
      energy requirements may not fully account for the different growth pattern of EBF
      infants. More studies in infants EBF to 6 months of age are needed to understand
      how growth of EBF infants influences energy requirements.

PMID- 23148917
TI  - Algorithms for modeling structural changes in human chromosomes.
AB  - Human cytogenetics is the study of chromosomes (typically at mitotic metaphase).
      The study of chromosomes has recently become integrated with molecular biology
      and genomics. Thus, it is an important part of genetics education. However, it is
      time consuming to train students and clinical technologists to recognize patterns
      of G-banded human chromosomes because of the dynamic nature of G-band resolutions
      in different metaphase spreads. Moreover, there are limited resources to obtain
      the images of abnormal chromosomes. We present in this paper an advanced version
      of computer based interactive tutorial program capable of simulating chromosome
      abnormalities, altering chromosome shapes, and manipulating G-band resolutions
      for human cytogenetic seduction. By simulating chromosomes using digital image
      processing and pattern recognition, the versatile software, together with various
      strategies such as website links and dialogs, will provide students with a
      virtual learning environment for self-practicing and testing, thus transforming
      the traditionally dry and ineffective approach into an exciting and efficient
      learning process.

PMID- 23148916
TI  - Reward and relief craving tendencies in patients with alcohol use disorders:
      results from the PREDICT study.
AB  - BACKGROUND: Previous research suggests that patients' tendencies toward either
      reward or relief craving are distinct continuous factorial dimensions of craving
      for alcohol. According to these tendencies patients with alcohol use disorders
      (AUD) might also be allocated into distinct subgroups. In personalized treatment,
      patients of such different subgroups might respond differently to various
      psychotherapeutic and pharmacological interventions aimed at relapse prevention.
      OBJECTIVES: To establish that the items of the subscale Temptation to Drink of
      the Alcohol Abstinence Self-Efficacy Scale (AASE) capture two continuous
      dimensions of reward and relief craving, and that they allow the identification
      of respective discrete class factors and subgroups of patients with AUD. METHODS:
      Nonlinear confirmatory factor analysis (CFA) and latent class factor analysis
      (LCFA) were performed with data from 426 detoxified patients with AUD. The
      validity of continuous relief and reward dimensions, discrete class factors, and
      subtypes with different craving tendencies was established by including past
      drinking in positive and negative settings, gender, trait anxiety and perceived
      stress as covariates in the finally accepted CFA and LCFA measurement models.
      RESULTS: The AASE temptation items formed two continuous relief and reward
      craving factors. They also associated themselves to two binary class factors,
      which defined four craving subgroups. Two of them (21% and 29% of patients) were
      characterized by high levels of either reward or relief craving tendencies. A
      third subgroup (31%) rated both tendencies in an equal high measure, while a
      fourth (18%) reported almost no craving tendencies at all. Past drinking in
      negative and positive settings was significantly associated with relief or reward
      craving tendencies. Male patients reported reward drinking more frequently than
      female patients. Trait anxiety was positively related only to the relief craving
      tendency. Unexpectedly, patients' level of perceived stress was associated with
      both craving tendencies. CONCLUSIONS: The AASE temptation items are suited to
      identify relief and reward craving dimensions and to assign patients to according
      subtypes. Thus, they can be used to screen for corresponding patient subgroups,
      possibly allowing allocation to interventions that are specifically tailored to
      patient's particular craving tendencies. Hence: A relatively simple psychometric
      measure could help in improving treatment outcomes through a personalized
      approach to intervention.

PMID- 23148918
TI  - [Process management in the hospital pharmacy for the improvement of the patient
      safety].
AB  - OBJECTIVES: To define a process management model for a hospital pharmacy in order
      to measure, analyse and make continuous improvements in patient safety and
      healthcare quality. MATERIAL AND METHODS: In order to implement process
      management, Igualada Hospital was divided into different processes, one of which
      was the Hospital Pharmacy. A multidisciplinary management team was given
      responsibility for each process. For each sub-process one person was identified
      to be responsible, and a working group was formed under his/her leadership. With
      the help of each working group, a risk analysis using failure modes and effects
      analysis (FMEA) was performed, and the corresponding improvement actions were
      implemented. Sub-process indicators were also identified, and different process
      management mechanisms were introduced. RESULTS: The first risk analysis with FMEA
      produced more than thirty preventive actions to improve patient safety. Later,
      the weekly analysis of errors, as well as the monthly analysis of key process
      indicators, permitted us to monitor process results and, as each sub-process
      manager participated in these meetings, also to assume accountability and
      responsibility, thus consolidating the culture of excellence. CONCLUSIONS: The
      introduction of different process management mechanisms, with the participation
      of people responsible for each sub-process, introduces a participative management
      tool for the continuous improvement of patient safety and healthcare quality.

PMID- 23148920
TI  - Hydrogen sulfide increases nitric oxide production with calcium-dependent
      activation of endothelial nitric oxide synthase in endothelial cells.
AB  - Hydrogen sulfide (H(2)S) was recently discovered to be synthesized in mammalian
      tissues by several different enzymes. Numerous studies have shown that H(2)S has
      vasodilator and antihypertensive effects in the cardiovascular system. However,
      intracellular mechanisms of the H(2)S-induced vasodilation and its interactions
      with other endothelium-derived relaxing factors, such as nitric oxide (NO),
      remain unclear. We investigated whether H(2)S directly regulates endothelial NO
      synthase (eNOS) activity and NO production in endothelial cells. NaHS, a H(2)S
      donor, dose-dependently increased NO production in cultured endothelial cells.
      This effect was abolished by a calcium chelator (BAPTA-AM), but not by the
      absence of extracellular calcium. The NaHS-induced NO production was partially
      blocked by inhibitors of ryanodine receptor (dantrolene) or inositol 1,4,5
      triphosphate receptor (xestospongin C). NaHS significantly increased
      intracellular calcium concentrations, and this effect was attenuated by
      dantrolene or xestospongin C. NaHS induced phosphorylation of eNOS at the
      activating phosphoserine residue 1179. The NaHS-induced eNOS phosphorylation and
      NO production were not affected by a PI3K/Akt inhibitor (wortmannin). The data of
      this study suggest that H(2)S directly acts on endothelial cells to induce eNOS
      activation and NO production by releasing calcium from the intracellular store in
      endoplasmic reticulum, which may explain one of mechanisms of its vasodilator
      function.

PMID- 23148919
TI  - External Evaluation of Population Pharmacokinetic Models of Vancomycin in
      Neonates: The transferability of published models to different clinical settings.
AB  - BACKGROUND: Vancomycin is one of the most evaluated antibiotics in neonates using
      modeling and simulation approaches. However no clear consensus on optimal dosing
      has been achieved. The objective of the present study was to perform an external
      evaluation of published models, in order to test their predictive performances in
      an independent dataset and to identify the possible study-related factors
      influencing the transferability of pharmacokinetic models to different clinical
      settings. METHOD: Published neonatal vancomycin pharmacokinetic models were
      screened from the literature. The predictive performance of 6 models was
      evaluated using an independent dataset (112 concentrations from 78 neonates). The
      evaluation procedures used simulation-based diagnostics (visual predictive check
      [VPC] and normalized prediction distribution errors [NPDE]). RESULTS: Differences
      in predictive performances of models for vancomycin pharmacokinetics in neonates
      were found. The mean of NPDE for 6 evaluated models were 1.35, -0.22, -0.36,
      0.24, 0.66, 0.48, respectively. These differences were explained, at least
      partly, by taking into account the method used to measure serum creatinine
      concentrations. The adult conversion factor of 1.3 (enzymatic to Jaffe) was
      tested with an improvement in the VPC and NPDE, but it still need to be evaluated
      and validated in neonates. Differences were also identified between analytical
      methods for vancomycin. CONCLUSION: The importance of analytical techniques for
      serum creatinine concentrations and vancomycin as a predictor of vancomycin
      concentrations in neonates has been confirmed. Dosage individualisation of
      vancomycin in neonates should consider not only patients' characteristics and
      clinical conditions, but also the methods used to measure serum creatinine and
      vancomycin.

PMID- 23148921
TI  - Maternal fecundity and asthma among offspring-is the risk programmed
      preconceptionally? Retrospective observational study.
AB  - OBJECTIVE: To evaluate the association between maternal fecundity factors and
      time to pregnancy and risk of asthma in offspring. DESIGN: Retrospective
      observational hospital-based birth cohort study. SETTING: A university-based
      obstetrics and gynecology department. PATIENT(S): A total of 40,914 women, who
      delivered between 1989 and 2007, were linked with the register for asthma
      reimbursement (n = 2,577) for their offspring. Fecundity factors were recorded
      during pregnancy. Logistic regression analyses were used. INTERVENTION(S): None.
      MAIN OUTCOME MEASURE(S): Asthma among offspring. RESULT(S): The risk of asthma
      was significantly increased if the mother had any infertility problems (adjusted
      odds ratio [adjusted OR] 1.39, 95% confidence interval [CI] 1.19-1.63), medical
      infertility treatment (aOR 1.43, 95% CI 1.13-1.80), or any infertility treatment
      (aOR 1.50, 95% CI 1.26-1.79). The risk of asthma among offspring was also higher
      among mothers who had more than two miscarriages (aOR 1.25, 95% CI 1.04-1.51) and
      time to pregnancy over 3 months (aOR 1.25, 95% CI 1.07-1.45). CONCLUSION(S):
      These findings suggest that maternal subfertility exposes offspring to an
      increased risk of asthma. CLINICAL TRIAL REGISTRATION NUMBER: The study is
      registered in Kuopio University Hospital register (TUTKI): ID 5302448.

PMID- 23148922
TI  - Investigation of gene expression profiles before and after embryonic genome
      activation and assessment of functional pathways at the human metaphase II oocyte
      and blastocyst stage.
AB  - OBJECTIVE: To compare the oocyte versus the blastocyst transcriptome and provide
      data on molecular pathways before and after embryonic genome activation. DESIGN:
      Prospective laboratory research study. SETTING: An IVF clinic and a specialist
      preimplantation genetics laboratory. PATIENT(S): Couples undergoing or having
      completed IVF treatment donating surplus oocytes or cryopreserved blastocysts
      after patient consent. INTERVENTION(S): Sets of pooled metaphase II (MII) oocytes
      or blastocysts were processed for RNA extraction, RNA amplification, and analysis
      with the use of the Human Genome Survey Microarrays v2.0 (Applied Biosystems).
      MAIN OUTCOME MEASURE(S): Association of cell type and gene expression profile.
      RESULT(S): Totals of 1,909 and 3,122 genes were uniquely expressed in human MII
      oocytes and human blastocysts respectively, and 4,910 genes were differentially
      expressed between the two sample types. Expression levels of 560 housekeeping
      genes, genes involved in the microRNA processing pathway, as well as hormones and
      hormone receptors were also investigated. CONCLUSION(S): The lists of genes
      identified may be of use for understanding the processes involved in early embryo
      development and blastocyst implantation, and for identifying any dysregulation
      leading to infertility.

PMID- 23148923
TI  - The impact of surgical sperm retrieval on the in vitro fertilization outcomes of
      infertile patients with temporary ejaculation failure on their oocyte retrieval
      day.
AB  - OBJECTIVE: To evaluate the impact of testicular sperm aspiration on the clinical
      outcomes of IVF patients with temporary ejaculation failure (TEF) on the day of
      oocyte retrieval. DESIGN: A case-control study. SETTING: University-affiliated
      IVF center. PATIENT(S): One hundred eight infertile couples encountering TEF on
      the day of oocyte retrieval. INTERVENTION(S): Testicular sperm aspiration and
      intracytoplasmic sperm injection (TESA-ICSI) were employed to help the TEF
      couples to complete their IVF treatments. A group of obstructive azoospermia (OA)
      patients was chosen as a control group to evaluate the efficiency and safety of
      this intervention. MAIN OUTCOME MEASURE(S): Fertilization rates, transferable
      embryo rates, and clinical pregnancy rates (PRs). RESULT(S): Through the TESA
      ICSI, TEF couples achieved a 38.83% (40/103) clinical PR per IVF cycle. Compared
      with the OA group, the TEF group showed a comparable fertilization rate (66.43%
      vs. 65.25%), transferable embryo rate (60.76% vs. 60.85%), and PR (51.61% vs.
      50.00%) in thawed ET cycles but a relatively low PR (25.49% vs. 44.64%) in fresh
      ET cycles. CONCLUSION(S): TESA-ICSI is a relatively efficient and safe way to
      help the patients encountering TEF.

PMID- 23148924
TI  - Down-regulation of CatSper1 channel in epididymal spermatozoa contributes to the
      pathogenesis of asthenozoospermia, whereas up-regulation of the channel by Sheng
      Jing-San treatment improves the sperm motility of asthenozoospermia in rats.
AB  - OBJECTIVE: To determine the expression of CatSper1 channel in epididymal
      spermatozoa in a rat model of asthenozoospermia, induced by cyclophosphamide
      (CP), and further examine the effects of soluble granules of Sheng-Jing-San
      (SJS), a traditional Chinese medicine recipe, on CatSper1 expression and sperm
      motility in the CP-induced asthenozoospermic rats. DESIGN: Placebo-controlled,
      randomized trial. SETTING: Neuroscience Research Institute, Peking University,
      China. ANIMAL(S): Sexually mature male Sprague-Dawley rats (n = 60).
      INTERVENTION(S): In the CP group, CP at the dose of 35 mg/kg intraperitoneally
      injected into rats once a day for 7 days; in the normal saline (NS) group, 0.9%
      saline solution was injected as control. MAIN OUTCOME MEASURE(S): Sperm motility
      and count were evaluated by computer-assisted sperm assay (CASA); protein and
      mRNA expression of CatSper1 channel in epididymal spermatozoa was determined by
      Western blotting and quantitative real-time RT-PCR, respectively. RESULT(S): The
      rats were randomly divided into five groups with 12 rats in each group: CP,
      normal saline (NS), CP + SJS, CP + NS, and treatment naive. In the CP + SJS
      group, after the last injection of CP, SJS at a dose of 30 mg/kg was
      intragastrically administrated to rats once a day for 14 days; in CP + NS group,
      saline solution instead of SJS was administrated as control. In the treatment
      naive group, rats were normally fed for 21 days as controls. We found a
      statistically significant reduction of the CatSper1 channel, which is associated
      with an impairment of sperm motility in the epididymal spermatozoa of CP-induced
      asthenozoospermic rats. Soluble granules of SJS could dramatically restore the CP
      induced down-regulation of CatSper1 in epididymal spermatozoa, which greatly
      improved the sperm motility in the asthenozoospermic rats. CONCLUSION(S): Down
      regulation of the CatSper1 channel in epididymal spermatozoa likely contributes
      to the pathogenesis of asthenozoospermia, whereas up-regulation of the channel by
      SJS improves sperm motility and thus can be used as an effective therapeutic
      strategy for the treatment of male infertility diagnosed with asthenozoospermia.

PMID- 23148925
TI  - Induction of endometriotic nodules in an experimental baboon model mimicking
      human deep nodular lesions.
AB  - OBJECTIVE: To establish an experimental model for the study of deep nodular
      endometriosis. DESIGN: Induction of nodular endometriosis in baboons by grafting
      different uterine specimens to the peritoneal cavity. SETTING: Research and
      university facilities. ANIMAL(S): Ten baboons, to develop a model of induced deep
      nodular endometriosis. INTERVENTION(S): Biopsies of endometrium, and endometrium
      plus the junctional zone (JZ), full uterine thickness, and myometrium grafted to
      the peritoneum. MAIN OUTCOME MEASURE(S): Macroscopic descriptions recorded for
      observed induced lesions; staining with hematoxylin and eosin for histological
      evaluation and specific antibodies (CK22, CD10) for immunohistochemical studies;
      and analysis of surface area and volume of lesions, glandular density, and
      invasion of surrounding organs. RESULT(S): The incidence of induced nodular
      endometriosis was 100%, but the extent depended on the tissue grafted. Lesions
      induced after grafting specimens containing the JZ were statistically
      significantly larger than those not containing the JZ. Surrounding organ invasion
      was reported in more than 40% of lesions after grafting specimens containing the
      JZ. CONCLUSION(S): The first experimental model of nodular endometriosis allows
      investigation of deeper nodular lesions as well as invasion phenomena associated
      with nodular lesions.

PMID- 23148926
TI  - The other side of the fertility coin: a comparison of childless men's and women's
      knowledge of fertility and assisted reproductive technology.
AB  - OBJECTIVE: To determine childless men's knowledge about fertility and assisted
      reproductive technology (ART) treatments and family building options, compared to
      knowledge of a sample of childless women. DESIGN: Self-report questionnaire
      comprising 2 self-ratings and 20 knowledge questions related to later
      childbearing and ART. SETTING: Online survey. PATIENT(S): A total of 599 presumed
      fertile, childless men between the ages of 20 and 50 years. INTERVENTION(S):
      None. MAIN OUTCOME MEASURE(S): Knowledge of fertility and ART as measured by the
      male version of the Fertility Awareness Survey. RESULT(S): The majority of
      participants rated themselves as having some knowledge or being fairly
      knowledgeable about fertility and ART. However, on the 20 knowledge questions,
      overall knowledge was limited, with more than 50% of the sample answering
      correctly only 4 of 20 knowledge questions. The men demonstrated even less
      knowledge of fertility and ART than childless women. CONCLUSION(S): Given that
      the childless men in our study had no coherent body of knowledge regarding age
      related fertility and ART treatment and family-building options, men may be
      contributing to the trend to delay childbearing. If they are to be effective in
      supporting informed fertility and childbearing decisions, education programs must
      target both women and men.

PMID- 23148927
TI  - Real-time Raman microspectroscopy scanning of the single live sperm bound to
      human zona pellucida.
AB  - OBJECTIVE: To determine if Raman microspectroscopy (RMS) can distinguish sperm
      bound to the human zona pellucida (ZP) from those unbound sperm. DESIGN: Paired
      experiments to compare Raman scanning features of ZP-bound and unbound sperm.
      SETTING: Public hospital-based clinical assisted reproduction center. PATIENT(S):
      Sperm samples from ten fertile donors were used in this study. INTERVENTION(S):
      None. MAIN OUTCOME MEASURE(S): Sperm-ZP binding, ZP-induced acrosome reaction,
      and scanning intensity of various regions of sperm. RESULT(S): The RMS found two
      slightly low-intensity regions (800-900 and 3,200-4,000 cm(-1)) shifted to high
      intensity grade at the acrosome region of the ZP-bound sperm compared with
      unbound sperm. Moreover, principal component analysis and statistical analysis
      showed that the RMS can distinguish the ZP-bound sperm from the unbound sperm.
      CONCLUSION(S): RMS scanning of single live sperm could be used to distinguish ZP
      bound sperm from unbound sperm. Thus, RMS may be a useful tool to detect normal
      functional sperm and to select sperm for intracytoplasmic sperm injection.

PMID- 23148928
TI  - An investigation of the resolution of inflammation (catabasis) in COPD.
AB  - BACKGROUND: Chronic Obstructive Pulmonary Disease (COPD) is characterized by an
      enhanced inflammatory response to smoking that persists despite quitting. The
      resolution of inflammation (catabasis) is a complex and highly regulated process
      where tissue resident macrophages play a key role since they phagocytose
      apoptotic cells (efferocytosis), preventing their secondary necrosis and the
      spill-over of their pro-inflammatory cytoplasmic content, and release pro
      resolution and tissue repair molecules, such as TGFbeta, VEGF and HGF. Because
      inflammation does not resolve in COPD, we hypothesized that catabasis may be
      abnormal in these patients. METHODS: To explore this hypothesis, we studied lung
      tissue samples obtained at surgery from 21 COPD patients, 22 smokers with normal
      spirometry and 13 non-smokers controls. In these samples we used: (1)
      immunohistochemistry to assess the expression of CD44, CD36, VEGF and TGFbeta in
      lung macrophages; (2) real time PCR to determine HGF, PPARgamma, TGFbeta, VEGF
      and MMP-9 gene expression; and, (3) ELISA to quantify lipoxin A4, a lipid
      mediator of catabasis. RESULTS: We found that current and former smokers with
      COPD showed: (1) more inflammation (higher MMP-9 expression); (2) reduced
      macrophage surface expression of CD44, a key efferocytosis receptor; and, (3)
      similar levels of TGFbeta, VEGF, HGF, PPARgamma, and lipoxin A4 than smokers with
      normal spirometry, despite the presence of inflammation and disease. CONCLUSIONS:
      These results identify several potential abnormalities of catabasis in patients
      with COPD.

PMID- 23148929
TI  - Pharmacists' roles in cancer pain control: A model in developing China.

PMID- 23148931
TI  - Effects of functional impairment on internalizing symptom trajectories in
      adolescence: a longitudinal, growth curve modelling study.
AB  - Despite the fact that psychosocial and functional impairment has long been
      acknowledged as an important aspect of psychiatric diagnosis and treatment,
      relatively little is known about the longitudinal relationship between
      psychiatric symptoms and functional impairment. This is particularly true in
      childhood and adolescence. Understanding how symptoms relate to functional
      impairment is of great importance to clinicians and researchers as it is
      essential to nosology, treatment, and prognosis. This study sought to understand
      the developmental relationship between internalizing symptoms, functional
      impairment and gender in a sample of youth aged 10-15 using growth curve methods.
      Key findings indicate that the presence of functional impairment was associated
      with increased baseline internalizing symptoms scores but had no effect on the
      slope of internalizing symptoms trajectories during adolescence. The study
      highlights that the association between internalizing symptoms and functional
      impairment appears to be constant, linear and does not vary by gender.

PMID- 23148930
TI  - A novel niche for skin derived precursors in non-follicular skin.
AB  - BACKGROUND: Skin derived precursors (SKP) comprise a subset of specialized dermal
      cells that can be distinguished from fibroblast by their capacity for spheroidal
      growth. Recent investigations have shown that hair follicles constitute a niche
      for this cell type, but their localization and their definite function in non
      follicular skin remains largely unknown. OBJECTIVE: To identify the dermal niche
      of non-follicular SKPs and to analyze whether functional aspects correlate with
      this localization. METHODS: SKPs were isolated from separate anatomical regions
      of human abdominal skin. Fluorescence activated cell sorting then was used to
      obtain a pure population of non-follicular SKPs. Functional characterization of
      these cells was performed applying differentiation and proliferation assays.
      Information on specific in vivo functions was derived from histological
      evaluation of quantity and localization patterns. RESULTS: Sphere forming
      capacity and differentiation assays show that SKPs reside in the papillary part
      of the dermis. Further delineation revealed that the dermal capillaries represent
      a niche for these cells which subsequently could be isolated by FACS utilizing a
      perivascular marker. Whereas functional properties described for follicular SKPs
      could also be detected in the perivascular SKP population, histological analyses
      additionally point to a cross-talk with epidermal stem cells and a reduction
      during chronological aging. CONCLUSION: Our data show that SKPs isolated from non
      follicular skin originate from a perivascular niche. Compared to their follicular
      counterparts, no functional differences could be observed upon cultivation, but
      ex vivo analyses also point to unique functions and a contribution to the
      phenotype of aged skin.

PMID- 23148932
TI  - Prognostic factors and recurrence pattern in node-negative advanced gastric
      cancer.
AB  - AIMS: Despite better overall survival in node-negative advanced gastric cancer
      (AGC), a significant proportion of patients develop recurrence and they may
      benefit from adjuvant therapy. The aim of this study was to evaluate the
      prognostic factors and recurrence pattern of node-negative AGC. METHODS: A total
      of 424 patients who underwent curative gastrectomy with extended lymphadenectomy
      for node-negative AGC between 2003 and 2005 were retrospectively reviewed.
      Patients with tumor involvement of adjacent organs (T4b), gastric cancer
      recurrence, tumor in the remnant stomach, less than 15 harvested lymph nodes, and
      those who received neoadjuvant chemotherapy were excluded. RESULTS: Invasion to
      deeper layers, undifferentiated histology, signet ring cell type compared with
      tubular adenocarcinoma, and tumor size larger than 6.3 cm correlated with poorer
      prognosis in univariate analysis. In multivariate one, however, only
      differentiation and depth of invasion, especially the presence of serosa
      involvement were significant. The 5-year survival rates of the four groups
      classified by differentiation and depth of invasion [T2/3 (differentiated type),
      T2/3 (undifferentiated type), T4a (differentiated type), and T4a
      (undifferentiated type)] were 98%, 92%, 80%, and 72%, respectively (P < 0.01). In
      terms of recurrence pattern, Lauren's type and depth of invasion were
      significant. Recurrence with peritoneal seeding was associated with the diffuse
      type and invasion into the subserosa or serosa, while hematogenous metastasis was
      related to the intestinal type and invasion to the proper muscle or subserosa
      layer. CONCLUSIONS: Differentiation and serosa involvement should be considered
      to stratify patients with node-negative AGC for adjuvant treatment.

PMID- 23148933
TI  - The role of shifting, updating, and inhibition in prospective memory performance
      in young and older adults.
AB  - Prospective memory performance shows a decline in late adulthood. The present
      article examines the role of 3 main executive function facets (i.e., shifting,
      updating, and inhibition) as possible developmental mechanisms associated with
      these age effects. One hundred seventy-five young and 110 older adults performed
      a battery of cognitive tests including measures of prospective memory, shifting,
      updating, inhibition, working memory, and speed. Age effects were confirmed in
      prospective memory and also obtained in shifting, updating, and inhibition. Yet,
      facets of executive control differently predicted prospective memory performance:
      While inhibition and shifting were strong predictors of prospective memory
      performance and also explained age differences in prospective memory, updating
      was not related to prospective memory performance across adulthood. Furthermore,
      considering executive function measures increased the amount of explained
      variance in prospective remembering and reduced the influence of speed. Working
      memory was not revealed to serve as a significant predictor of prospective memory
      performance in the present study. These findings clarify the role of different
      facets of controlled attention on age effects in prospective memory and bear
      important conceptual implications: Results suggest that some but not all facets
      of executive functioning are important developmental mechanisms of prospective
      memory across adulthood beyond working memory and speed. Specifically, inhibition
      and shifting appear to be essential aspects of cognitive control involved in age
      related prospective memory performance.

PMID- 23148934
TI  - Patterns and sources of continuity and change of energetic and temporal aspects
      of temperament in adulthood: A longitudinal twin study of self- and peer reports.
AB  - This study investigated the mean-level and individual-level trends as well as the
      genetic and environmental sources of rank-order continuity and change in
      temperament traits (Briskness, Perseveration, Sensory Sensitivity, Emotional
      Reactivity, Endurance, and Activity). We analyzed self-reports and peer ratings
      from 2 adult age groups of twins, aged 15-30 (n = 348; 113 monozygotic and 61
      dizygotic twin pairs) and 31-67 (n = 352; 110 monozygotic and 66 dizygotic twin
      pairs), captured at 2 different points of time 13 years apart. Temperament traits
      were fairly stable accompanying high levels of heritability. However, they also
      undergo mean-level, individual-level, and rank-order changes. In young adulthood,
      rank-order change was due to both genetic and environmental factors, whereas in
      older adult years, rank-order change was predominantly attributable to
      environmental effects. Phenotypic rank-order continuity was larger for older
      adults due to higher genetic as well as environmental continuity. For specific
      temperament traits (e.g., Activity), environmental variance proportionally
      increased across adulthood compared with genetic variance resulting in decreasing
      levels of heritability, whereas the reverse was found for other traits (e.g.,
      Endurance). Specifics regarding the traits studied were discussed. The results
      indicate a complex interplay between genetic and environmental sources resulting
      in continuity and change of temperament across adulthood.

PMID- 23148935
TI  - Stability and change in intelligence from age 12 to age 52: results from the
      Luxembourg MAGRIP study.
AB  - The present longitudinal study tackled 2 key aspects of the development of
      intelligence across a 40-year time period from age 12 to age 52 concerning (a)
      stability and change in the structure of intelligence with reference to the age
      differentiation-dedifferentiation hypothesis (how different cognitive abilities
      relate to each other across age) and (b) differential stabilities (the rank
      ordering of persons' intelligence levels across time). To this end, we drew on 2
      structural conceptions of intelligence: (a) the extended Gf-Gc model to study
      broad cognitive abilities and (b) the 3-stratum model to decompose cognitive
      change into processes that are shared by all broad abilities (attributable to
      general cognitive ability g) and processes specific to a certain ability
      (independent of g). Data were obtained for 344 persons (56.4% female). The
      results showed that people differ more greatly over time with respect to all
      broad abilities except for fluid reasoning, whereas the rank ordering of persons
      on all broad abilities remains remarkably stable. These combined results yielded
      substantial gap-widening effects from age 12 to age 52 years that were mainly
      accounted for by a substantial increase in g variance in combination with a high
      differential stability of g. Moreover, the increase in g variance reflects an
      increase in covariance among different broad abilities, which indicates that the
      different constructs relate more closely to each other at age 52 compared to age
      12 (i.e., age dedifferentiation). Two theoretical explanations of this change in
      the structure of intelligence are discussed (common cause hypothesis and
      investment theory).

PMID- 23148937
TI  - Preschoolers can make highly accurate judgments of learning.
AB  - Preschoolers' ability to make judgments of learning (JOLs) was examined in 3
      experiments in which they were taught proper names for animals. In Experiment 1,
      when judgments were made immediately after studying, nearly every child predicted
      subsequent recall of every name. When judgments were made after a delay, fewer
      showed this response tendency. The delayed JOLs of those who predicted at least 1
      recall failure were still overconfident, however, and were not correlated with
      final recall. In Experiment 2, children received a second study trial with
      feedback, made JOLs after a delay, and completed an additional forced-choice
      judgment task. In this task, an animal whose name had been recalled was pitted
      against an animal whose name had not been recalled, and the children chose the
      one they were more likely to remember later. Compared with Experiment 1, more
      children predicted at least 1 recall failure and predictions were moderately
      accurate. In the forced-choice task, animal names that had just been successfully
      recalled were typically chosen over ones that had not. Experiment 3 examined the
      effect of providing an additional retrieval attempt on delayed JOLs. Half of the
      children received a single study session, and half received an additional study
      session with feedback. Children in the practice group showed less overconfidence
      than those in the no-practice group. Taken together, the results suggest that,
      with minimal task experience, most preschoolers understand that they will not
      remember everything and that if they cannot recall something at present, they are
      unlikely to recall it in the future.

PMID- 23148936
TI  - Children's competence or adults' incompetence: different developmental
      trajectories in different tasks.
AB  - Dual-process theories have been proposed to explain normative and heuristic
      responses to reasoning and decision-making problems. Standard unitary and dual
      process theories predict that normative responses should increase with age.
      However, research has focused recently on exceptions to this standard pattern,
      including developmental increases in heuristic or intuitive responses.
      Developmental trends for normative and heuristic responses were investigated for
      2 kinds of causal reasoning (if-only and covariation) problems in 2 experiments.
      To investigate the role of superstitious thinking in these developmental trends,
      in both experiments a superstitious element was added to the problem solved by
      half the participants. In the first experiment, 90 fifth graders, 99 seventh
      graders, and 153 adults responded to an if-only problem. Children performed
      better than adults, with normative responses decreasing and heuristic responses
      increasing with age. A superstitious jinx intended to reduce heuristic responses
      had little effect for all age groups. In the second experiment, 276 fifth
      graders, 344 seventh graders, and 90 adults responded to a covariation-detection
      problem. When win-loss ratios were equal, adults performed better than children,
      with normative responses increasing and heuristic responses decreasing with age.
      When win-loss ratios were strikingly different, however, even the youngest
      children were able to solve the problems correctly; participants of all ages
      responded about equally well. When the normative response required recognizing
      that a good-luck ritual led to better team performance, participants in all age
      groups responded skeptically that the ritual had no effect, illustrating belief
      bias. These results are discussed in terms of dual-process theories and the
      development of heuristic (or intuitive) and analytical processes.

PMID- 23148938
TI  - Just pretending can be really learning: children use pretend play as a source for
      acquiring generic knowledge.
AB  - Children can acquire generic knowledge by sharing in pretend play with more
      knowledgeable partners. We report 3 experiments in which we investigated how this
      learning occurs-how children draw generalizations from pretense, and whether they
      resist doing so for pretense that is unrealistic. In all experiments,
      preschoolers watched pretend scenarios about an animal and were then asked
      questions about real animals. In Experiment 1, 3- and 4-year-olds treated the
      pretend scenarios as informative about the kind of animal represented in the
      pretense but as uninformative about another kind of animal. In Experiments 2 and
      3, 4- and 5-year-olds resisted learning from scenarios that contradicted their
      existing knowledge and expectations. Together, these findings show that
      children's learning from pretense shows specificity for the kinds represented in
      pretense and that children's learning from pretense is selective.

PMID- 23148939
TI  - Information management strategies within conversations about cigarette smoking:
      parenting correlates and longitudinal associations with teen smoking.
AB  - The present study examined smoking-specific and general parenting predictors of
      in vivo observed patterns of parent-adolescent discussion concerning adolescents'
      cigarette smoking experiences and associations between these observed patterns
      and 24-month longitudinal trajectories of teen cigarette smoking behavior
      (nonsmokers, current experimenters, escalators). Parental solicitation,
      adolescent disclosure, and adolescent information management were coded from
      direct observations of 528 video-recorded parent-adolescent discussions about
      cigarette smoking with 344 teens (M age = 15.62 years) with a history of smoking
      experimentation (321 interactions with mothers, 207 interactions with fathers).
      Adolescent initiation of discussions concerning their own smoking behavior (21%
      of interactions) was predicted by lower levels of maternal observed disapproval
      of cigarette smoking and fewer teen-reported communication problems with mothers.
      Maternal initiation in discussions (35% of interactions) was associated with
      higher levels of family rules about illicit substance use. Three categories of
      adolescent information management (full disclosure, active secrecy, incomplete
      strategies) were coded by matching adolescents' confidential self-reported
      smoking status with their observed spontaneous disclosures and responses to
      parental solicitations. Fully disclosing teens reported higher quality
      communication with their mothers (more open, less problematic). Teens engaged in
      active secrecy with their mothers when families had high levels of parental rules
      about illicit substance use and when mothers expressed lower levels of
      expectancies that their teen would smoke in the future. Adolescents were more
      likely to escalate their smoking over 2 years if their parents initiated the
      discussion of adolescent smoking behavior (solicited) and if adolescents engaged
      in active secrecy.

PMID- 23148940
TI  - Combination of LC-MS- and GC-MS-based metabolomics to study the effect of
      ozonated autohemotherapy on human blood.
AB  - Ozonated autohemotherapy (O3-AHT) is a medical approach during which blood
      obtained from the patient is ozonated and injected back into the body. Despite an
      increasing number of evidence that O3-AHT is safe, this type of therapy remains
      controversial. To extend knowledge about the changes in blood evoked by O3-AHT,
      LC-MS- and GC-MS-based metabolic fingerprinting was used to compare plasma
      samples obtained from blood before and after the treatment with potentially
      therapeutic concentrations of ozone. The procedure was performed in PVC bags
      utilized for blood storage to study also possible interactions between ozone and
      plastic. By use of GC-MS, an increase in lactic acid and pyruvic acid was
      observed, which indicated an increased rate of glycolysis. With LC-MS, changes in
      plasma antioxidants were observed. Moreover, concentrations of lipid oxidation
      products (LOP) and lysophospholipids were increased after ozone treatment. This
      is the first report of increased LOPs metabolites after ozonation of blood. Seven
      metabolites detected by LC-QTOF-MS only in ozonated samples could be considered
      as novel biomarkers of oxidative stress. Several plasticizers have been detected
      by both techniques in blood stored in PVC bags. PVC is known to be an ozone
      resistant material, but ozonation of blood in PVC bags stimulates leaching of
      plasticizers into the blood.

PMID- 23148941
TI  - The utility of the new research diagnostic criteria for Alzheimer's disease.

PMID- 23148942
TI  - Commentary on: "Cost: the missing outcome in simulation-based education research:
      a systematic review" by Zendejas et al.

PMID- 23148943
TI  - Mechanisms, indications and results of salvage systemic therapy for sporadic and
      von Hippel-Lindau related hemangioblastomas of the central nervous system.
AB  - Hemangioblastomas (HBs) are rare indolent vascular tumors that may occur
      sporadically or in association with von Hippel-Lindau (VHL) disease. Total
      neurosurgical resection is the standard upfront approach providing long-term
      tumor control. At time of tumor recurrence, second surgery, radiosurgery or
      radiotherapy are the main therapeutic strategies. Limited information is
      available on the role of pharmacological strategies. Anti-angiogenic agents,
      particularly multitarget tyrosine kinase inhibitors (semaxanib, sunitinib,
      vatalanib), thalidomide and interferon alfa-2a are currently the most widely
      studied strategies to prolonge disease stability. Salvage therapy with anti
      angiogenetic drugs may be of benefit in some patients who are not suitable for
      surgery, radiosurgery or radiotherapy, with progressive or recurrent
      hemangioblastoma especially those located in retina, since anti-angiogenetic
      therapy may delay tumor progression. This strategy warrants prospective
      evaluation in a clinical trial.

PMID- 23148945
TI  - Sorption studies on heavy metal removal using chitin/bentonite biocomposite.
AB  - Contamination of water by toxic heavy metals due to urbanization is a world-wide
      environmental problem, which changes chemical and biological properties of both
      surface and ground water. The heavy metals render the water unsuitable for
      drinking and are also highly toxic to human beings. Removal of heavy metals is
      therefore essential. Thus, in my present work batch adsorption studies have been
      used to remove the Cr(VI) from aqueous solution using chitin composite. The data
      obtained from batch method at optimized conditions have been subjected to
      Freundlich and Langmuir isotherm studies. The data were suitable for both models
      indicating favorability.

PMID- 23148944
TI  - Bovine serum albumin oligomers in the E- and B-forms at low protein concentration
      and ionic strength.
AB  - The manuscript describes the study of the oligomerization process of bovine serum
      albumin (BSA) in two different structural monomeric forms: the extended-form (E)
      at pH 2.0 and the basic-form (B) at pH 9.0. The study was conducted at low
      protein concentration (1mg/ml) and relatively short incubation time (maximum 56
      days) in order to investigate early oligomerization events rather than the
      formation of mature fibrils. The comparison between the two isoforms show that
      oligomers form much faster (~6 days) in the E-form than in the B-form where
      formation of oligomers requires ~4 weeks. The oligomers appear to be limited to a
      maximum of tetramers with size <30 nm. Hydrophobic interactions from exposed
      neutral amino acid residues in the elongated E-form are the likely cause for the
      quick formation of aggregates at acidic pH. We used an array of biophysical
      techniques for the study and determined that oligomerization occurs without
      further large changes in the secondary structure of the monomers. Under the
      conditions adopted in this study, aggregation does not seem to exceed the
      formation of tetramers, even though a very small amount of much larger aggregates
      seem to form.

PMID- 23148946
TI  - Macromolecular crowding modulates the kinetics and morphology of amyloid self
      assembly by beta-lactoglobulin.
AB  - The formation of amyloid fibrils by beta-lactoglobulin in the presence of GndHCl
      has been monitored by using thioflavin T (ThT) fluorescence, Congo Red and
      transmission electron microscopy (TEM). Large quantities of aggregated protein
      are formed by incubating beta-lactoglobulin in 2M GndHCl at room temperature and
      pH 7.0 for about 20 days. The kinetics of fibrillation process can be described
      by the lag time for formation of stable nuclei (nucleation) and the apparent rate
      constant for the growth of fibrils (elongation). Moreover, the effects of
      macromolecular crowding agents, Dextran 70 and polyethylene glycols (PEG), on the
      amyloid formation of beta-lactoglobulin at pH 7.0 are studied. The results show
      that the increase in macromolecular crowding agent concentrations results in
      shorter lag time and faster growth of fibrils. It proves that macromolecular
      crowding can effectively accelerate the fibril formation of beta-lactoglobulin at
      neutral pH. At the same time, it can be observed that the amplitude of the ThT
      fluorescence intensity decreases as the Dextran 70 concentration is increased.
      The observation suggests that the yield of amyloid fibrils is significantly
      reduced by the addition of macromolecular crowding agents. The conclusion is
      further confirmed by the transmission electron microscopy. In addition, the
      results of transmission electron microscopy also indicate that macromolecular
      crowding can alter the fibril morphology of beta-lactoglobulin. In brief, our
      findings demonstrate that the effects of macromolecular crowding are essential to
      the understanding of protein amyloid self-assembly occurring in vivo.

PMID- 23148947
TI  - Evaluation of in vitro antioxidant potency of exopolysaccharide from endophytic
      Fusarium solani SD5.
AB  - A potent endophytic fungus, Fusarium solani SD5 was used for exopolysaccharide
      (EPS) production. The isolated EPS were purified and major EPS fraction (PS-I);
      rhamno galactan was used to evaluate anti oxidant activities in vitro. EPS (PS-I)
      showed significant free radical scavenging effect on DPPH (1,1-diphenyl-2
      picrylhydrazyl) and scavenging potency is indicated by IC(50) value 578.541 +/-
      33.256 MUg/ml. EPS (PS-I) significantly induced antioxidant parameters of
      peritoneal macrophage cells at a concentration dependent manner and at 500 MUg/ml
      it showed maximum protective effect against free radicals [malondialdehyde (MDA)
      0.178 +/- 0.015; super oxide dismutase (SOD) 41.287 +/- 1.051; glutathione
      peroxidase (GPx) 30.182 +/- 1.237; reduced glutathione (GSH) 56.892 +/- 1.272;
      oxidized glutathione (GSSG) 8.458 +/- 0.768]. MTT [3-(4,5-dimethylthiazol-2-yl)
      2,5 diphenyltetrazolium bromide] cytotoxicity assay indicated that EPS (PS-I) had
      no significant cytotoxic effect (concentration up to 500 MUg/ml) on macrophage
      cells. Present findings suggested that the EPS (PS-I) may become a potential
      nontoxic exogenous antioxidant.

PMID- 23148948
TI  - WIN55, 212-2 promotes differentiation of oligodendrocyte precursor cells and
      improve remyelination through regulation of the phosphorylation level of the ERK
      1/2 via cannabinoid receptor 1 after stroke-induced demyelination.
AB  - In stroke, a common cause of neurological disability in adults is that the myelin
      sheaths are lost through the injury or death of mature oligodendrocytes, and the
      failure of remyelination may be often due to insufficient proliferation and
      differentiation of oligodendroglial progenitors. In the current study, we used
      middle cerebral artery occlusion (MCAO) to induced transient focal cerebral
      ischemia, and found that WIN55, 212-2 augmented actively proliferating
      oligodendrocytes measured by CC1 immunoreactive cells within the peri-infarct
      areas. To establish whether these effects were associated with changes in myelin
      formation, we analyzed the expression of myelin basic protein (MBP) and myelin
      ultrastructure. We found that WIN55, 212-2 showed more extensive remyelination
      than vehicle at 14 days post injection (dpi). The extracellular signal-regulated
      kinase/mitogen-activated protein kinase (ERK/MAPK) signaling pathway may be
      involved in OPCs differentiation. To determine the regulatory effect of WIN55,
      212-2 post-treatment on phospho-ERK 1/2 (p-ERK 1/2) after ischemia/reperfusion,
      Western blot analysis was performed. We found that WIN55, 212-2 regulated the
      phosphorylation level of the ERK 1/2 to promote OPCs survival and
      differentiation. Notably, cannabinoid receptor 1 is coupled to the activation of
      the ERK cascade. Following rimonabant combined treatment, the effect of WIN55,
      212-2 on regulating the phosphorylation level of the ERK 1/2 was reversed, and
      the effect of accelerated myelin formation was partially inhibited. Together, we
      first found that WIN55, 212-2 promoted OPCs differentiation and remyelination
      through regulation of the level of the p-ERK 1/2 via cannabinoid receptor 1.

PMID- 23148949
TI  - Pharmacological profile of engineered 5-HT4 receptors and identification of 5-HT4
      receptor-biased ligands.
AB  - G protein-coupled receptors (GPCRs) can activate simultaneously multiple
      signaling pathways upon agonist binding. The combined use of engineered GPCRs,
      such as the receptors activated solely by synthetic ligands (RASSLs), and of
      biased ligands that activate only one pathway at a time might help deciphering
      the physiological role of each G protein signaling. In order to find serotonin
      type 4 receptor (5-HT4R) biased ligands, we analyzed the ability of several
      compounds to activate the Gs and G(q/11) pathways in COS-7 cells that transiently
      express wild type 5-HT4R, the 5-HT4R-D(100)A mutant (known also as 5-HT4-RASSL,
      or Rs1) or the 5-HT4R-T(104)A mutant, which modifies agonist-induced 5-HT4R
      activation. This analysis allowed completing the pharmacological profile of the
      two mutant 5-HT4Rs, but we did not find any biased ligand for the mutant
      receptors. Conversely, we identified the first biased agonists for wild type 5
      HT4R. Indeed, RS 67333 and prucalopride acted as partial agonists to induce cAMP
      accumulation, but as antagonists on inositol phosphate production. Moreover, they
      showed very different antagonist potencies that could be exploited to study the
      activation of the G(s) pathway, with or without concomitant block of G(q/11)
      signaling. This article is part of a Special Issue entitled Optogenetics (7th
      BRES).

PMID- 23148951
TI  - An in vitro investigation of species-dependent intestinal transport of selenium
      and the impact of this process on selenium bioavailability.
AB  - A range of Se species has been shown to occur in a variety of different
      foodstuffs. Depending on its speciation, Se is more or less bioavailable to human
      subjects. In the present study, the role of speciation as a determinant of Se
      bioavailability was addressed with an investigation of species-specific
      mechanisms of transport at the intestinal level. The present work focused on four
      distinct Se compounds (selenate (Se(VI)), selenite (Se(IV)), selenomethionine
      (SeMet) and methylselenocysteine (MeSeCys)), whose intestinal transport was
      mimicked through an in vitro bicameral model of enterocyte-like differentiated
      Caco-2 cells. Efficiency of Se absorption was shown to be species dependent
      (SeMet > MeSeCys > Se(VI) > Se(IV)). In the case of SeMet, MeSeCys and Se(VI),
      the highly polarised passage from the apical to basolateral pole indicated that a
      substantial fraction of transport was transcellular, whilst results for Se(IV)
      indicated paracellular diffusion. Passage of the organic Se species (SeMet and
      MeSeCys) became saturated after 3 h, but no such effect was observed for the
      inorganic species. In addition, SeMet and MeSeCys transport was significantly
      inhibited by their respective S analogues methionine and methylcysteine, which
      suggests a common transport system for both kinds of compounds.

PMID- 23148952
TI  - Family nurse practitioners: "value add" in outpatient chronic disease management.
AB  - Nurse practitioners are capable leaders in primary care design as practices
      nationwide move to consider and adopt the patient-centered medical home. The
      chronic care model provides a structure to enhance the care of chronic illness.
      Nurse practitioners are instrumental in many areas of this model as both leaders
      and caregivers. Safety and quality are basic medical home goals; nurse
      practitioners enhance both. The addition of a nurse practitioner to a practice is
      an effective "value add" in every way.

PMID- 23148950
TI  - Honokiol protects brain against ischemia-reperfusion injury in rats through
      disrupting PSD95-nNOS interaction.
AB  - Honokiol, a major bioactive constituent of the bark of Magnolia officinalis has
      been confirmed to have the neuroprotective effect on ischemic stroke in rats.
      This study was designed to observe the therapeutic time window of honokiol
      microemulsion on cerebral ischemia-reperfusion injury to support its potential
      for future clinical trials and further explore the underlying mechanisms.
      Honokiol microemulsion (50MUg/kg, i.v. at 0, 1 or 3h after reperfusion)
      significantly reduced neurological deficit, infarct volume and brain water
      content in rats subjected to cerebral ischemia-reperfusion, and honokiol (0.1
      10MUM) significantly attenuated oxygen-glucose deprivation- or glutamate-induced
      injury of fetal rat cortical neurons. In co-immunoprecipitation and western blot
      test, honokiol decreased the intensity of nNOS related to PSD95 but failed to
      affect that of PSD95 related to NR2B in NR2B-PSD95-nNOS complex, and it also
      inhibited the translocation of nNOS from cytosol to membrane without affecting
      total nNOS expression, and then markedly decreased NO production in cortical
      neurons. Besides, the results of whole-cell patch-clamp recordings showed that
      honokiol reversibly inhibited the NMDA current by about 64%. In conclusion,
      honokiol has a therapeutic window of at least 5h after the onset of cerebral
      ischemia or 3h after reperfusion in rats, which may be in part ascribed to the
      disruption of the PSD95-nNOS interaction leading to the inhibition of neurotoxic
      NO production.

PMID- 23148953
TI  - Integration of behavioral medicine in primary care.
AB  - The health care system in the United States is inefficient and there are many
      incentives for sustainable changes in the delivery of care. Incorporating
      behavioral medicine offers a wide range of opportunities. Within primary care
      settings, pain disorders, addiction, depression, and anxiety disorders are highly
      prevalent. Numerous chronic health conditions also require behavioral support for
      lifestyle change. These disorders are optimally managed through interdisciplinary
      collaborations that include a behavioral medicine component. This article
      discusses the effective integration of behavioral medicine within a primary care
      patient-centered medical home and describes the organizational planning and
      structure required for success.

PMID- 23148954
TI  - Opportunities to improve clinical outcomes and challenges to implementing
      clinical pharmacists into health care teams.
AB  - Improving patient care outcomes is achieved through communication, collaboration,
      and coordination of care between various health care professionals in all health
      care practice settings. The foundation of this patient-centered model approach
      includes the recognition of pharmacists as drug therapy experts and, therefore,
      as members of the health care team who provide a unique set of knowledge and
      skills. This article focuses on improving clinical outcomes by integrating
      clinical pharmacists into health care teams, and addresses the obstacles and
      solutions to achieving this goal.

PMID- 23148955
TI  - Palliative care in the patient-centered medical home.
AB  - There are few published data on the delivery of palliative care services in the
      outpatient setting and virtually none on either the integration of palliative
      care into primary care practice or its applicability to innovative models of
      health care delivery, such as the patient-centered medical home and accountable
      care organizations. In this article, new topics for health services delivery
      research are suggested. Because of the lack of data, the article draws on
      information collected from inpatient palliative care delivery and includes
      anecdotal experiences from the outpatient pain medicine and palliative care
      clinic of an academic department of family medicine.

PMID- 23148956
TI  - Health information technology: medical record documentation issues in the
      electronic era.
AB  - This article outlines the regulatory movement propelling physicians into the
      electronic health record environment and the subsequent emergence of quality
      issues in the medical record. There are benefits and downside risks for
      implementing electronic health records as part of the desire of a practice or
      institution to build patient-centered medical homes. The intersection of how a
      practice or institution collects and reports quality metrics using health
      information technology and subsequently submits claims for services rendered has
      created unforeseen challenges for which leadership must be aware and address
      proactively.

PMID- 23148957
TI  - Utilizing international medical graduates in health care delivery: brain drain,
      brain gain, or brain waste? A win-win approach at University of California, Los
      Angeles.
AB  - After identifying many unlicensed Hispanic international medical graduates (IMGs)
      legally residing in southern California, University of California, Los Angeles
      developed an innovative program to prepare these sidelined physicians to enter
      family medicine residency programs and become licensed physicians. On completion
      of a 3-year family medicine residency-training program, these IMGs have an
      obligation to practice in a federally designated underserved community in the
      state for 2 to 3 years. As the US health care system moves from physician
      centered practices to patient-focused teams, with primary care serving as the
      foundation for building patient-centered medical homes, attention to educating
      IMGs in these concepts is crucial.

PMID- 23148958
TI  - Adoption of self-management interventions for prevention and care.
AB  - Seventy-five percent of health care costs can be attributed to chronic diseases,
      making prevention and management imperative. Collaborative patient self
      management in primary care is efficacious in reducing symptoms and increasing
      quality of life. In this article, the authors argue that self-management
      interventions span the continuum of prevention and disease management. Self
      management interventions rest on a foundation of 5 core actions: (1) activate
      motivation to change, (2) apply domain-specific information from education and
      self-monitoring, (3) develop skills, (4) acquire environmental resources, and (5)
      build social support. Several delivery vehicles are described and evaluated in
      terms of diffusion and cost-containment goals.

PMID- 23148960
TI  - Bending the cost curve and increasing revenue: a family medicine model that
      works!
AB  - This article attempts to illustrate ways in which family physician practices are
      able to demonstrate high value, enhanced quality, and streamlined costs,
      essential components of practice sustainability. Specific examples are provided
      to assist practices to consider questions and information that allow for skillful
      engagement during contract negotiations, consider increasing practice revenues by
      adopting practice enhancements that make sense for the location of the practice
      and community needs, develop workflow analyses, and review opportunities for
      expense reduction.

PMID- 23148959
TI  - Optimizing pain management through collaborations with behavioral and addiction
      medicine in primary care.
AB  - Chronic noncancer pain (CNCP) affects many primary care patients, and carries a
      large human and economic burden. In response to the widespread perception that
      pain is underdiagnosed and undertreated, regulatory bodies have encouraged more
      comprehensive services to address pain syndromes. Significant hurdles exist in
      treating CNCP in primary care settings, and interventional therapies and
      pharmacotherapy often do not provide complete symptomatic relief. This article
      describes a multidimensional and interdisciplinary approach to the treatment of
      CNCP. The utility of collaborations with behavioral and addiction medicine
      specialists optimizes care and advances models of patient treatment within a
      primary care patient-centered medical home.

PMID- 23148961
TI  - The playbook for primary care practice management.

PMID- 23148962
TI  - Primary care: clinics in office practice. Introduction.

PMID- 23148964
TI  - Atrial remodeling: new pathophysiological mechanism of atrial fibrillation.
AB  - Atrial fibrillation (AF), the most common sustained arrhythmia associated with
      substantial cardiovascular morbidity and mortality with stroke being the most
      critical complication. Most frequently, AF occurs in conjunction with other
      cardiovascular disease, such as hypertension, ischemic heart disease, valve
      disease or cardiac failure. Role of atrial remodeling has emerged as the new
      pathophysiological mechanism of atrial fibrillation. Experimental and clinical
      studies point at two major mechanisms involved in the intrinsically progressive
      nature of AF. The first consists of a change in the electrical properties of the
      atrium, notably a shortening of the AERP and a loss of rate adaptation, and hence
      was named electrical remodeling. Furthermore, based on data from is experimental
      models, it has been considered that AF is also associated with elaborate adaptive
      and maladaptive changes in tissue and cellular architecture. By parallel, this
      type of change was denominated structural remodeling. Together, these mechanisms
      will increase the probability of generating multiple atrial wavelets by enabling
      rapid atrial activation and dispersion of refractoriness.

PMID- 23148963
TI  - Treatment strategy for chronic low back pain.
AB  - The management of non-specific low back pain relies chiefly on analgesics,
      education, and physical exercises. Of the many risk factors for chronicity, the
      most relevant are psychosocial and occupational. Identifying homogeneous patient
      subgroups helps to develop personalized treatment strategies, thus improving the
      outcomes. Current clinical research is focusing on subgroup identification via
      simple validated questionnaires that are suitable for use in everyday practice.
      We suggest a management approach leading from the individual patient profile to
      the treatment strategy.

PMID- 23148965
TI  - Image-enhanced endoscopy for the diagnosis of colon neoplasms.

PMID- 23148966
TI  - Potential implications of the Nagoya Protocol for the livestock sector.

PMID- 23148967
TI  - Jim Crow: a great population geneticist.

PMID- 23148968
TI  - Farmer's views and values to focus on cattle conservation policies: the case of
      eight European countries.
AB  - Our aim was to identify elements useful in designing policies and programmes for
      conservation of farm animal genetic resources, taking as case study a group of
      European local cattle breeds. We first investigated the implications of
      differences among countries in the policies and programmes to be developed.
      Secondly, we analysed key elements common to countries, which may affect local
      breed viability. We used the herd size trend expected by the farmer in the near
      future as an indicator of breed viability. Fifteen breeds, for a total of 355
      farms, were surveyed. To take into account the multiple factors influencing
      breeds' demographic trends, the questionnaire included economical, technical and
      social aspects. Among the major differences across countries was the perception
      of the farmer on the value attributed to the local breed by society. Concerning
      the elements common to countries and their association to breed viability, the
      greater the collaboration among farmers and the stakeholders' appreciation as
      perceived by the farmer, the greater the viability of the farm. An opposite trend
      was observed for the age of the farmer. Older farmers generally planned to soon
      cease farming or decrease herd size, whereas young farmers planned to increase
      the size of their herds. Implications of including these elements in conservation
      policies are discussed.

PMID- 23148969
TI  - Developing a typology for local cattle breed farmers in Europe.
AB  - Recognizing cultural diversity among local breed farmers is crucial for the
      successful development and implementation of farm animal genetic resources FAnGr
      conservation policies and programmes. In this study based on survey data
      collected in the EUropean REgional CAttle breeds project from six European
      countries, a typology of local breed farmers was designed and profiles for each
      of the farmer types were developed to assist these policy needs. Three main
      farmer types were constructed: production-oriented, product and service-oriented
      and hobby-oriented farmers. In addition, seven subtypes were characterized under
      the main types: sustainable producers, opportunists, multi-users, brand makers,
      traditionalists, pragmatists and newcomers. These types have many similarities to
      the 'productivist', 'multifunctional' and 'post-productivist' farmer types. The
      typology not only reveals the high level of diversity among local cattle breed
      farmers in Europe, which presents an opportunity for the in situ conservation of
      animal genetic resources, but also a challenge for policy to meet the differing
      requirements of the farmer types.

PMID- 23148970
TI  - Genetic associations of visual scores with subsequent rebreeding and days to
      first calving in Nellore cattle.
AB  - Records of Nellore animals born from 1990 to 2006 were used to estimate genetic
      correlations of visual scores at yearling (conformation, C; finishing precocity,
      P; and muscling, M) with primiparous subsequent rebreeding (SR) and days to first
      calving (DC), because the magnitude of these associations is still unknown.
      Genetic parameters were estimated by multiple-traits Bayesian analysis, using a
      nonlinear (threshold) animal models for visual scores and SR and a linear animal
      models for weaning weight (WW) and DC. WW was included in the analysis to account
      for the effects of sequential selection. The posterior means of heritabilities
      estimated for C, P, M, SR and DC were 0.24 +/- 0.01, 0.31 +/- 0.01, 0.30 +/-
      0.01, 0.18 +/- 0.02 and 0.06 +/- 0.02, respectively. The posterior means of
      genetic correlations estimated between SR and visual scores were low and
      positive, with values of 0.09 +/- 0.02 (C), 0.19 +/- 0.03 (P) and 0.18 +/- 0.05
      (M). On the other hand, negative genetic correlations were found between DC and C
      (-0.11 +/- 0.09), P (-0.19 +/- 0.09) and M (-0.16 +/- 0.09). The primiparous
      rebreeding trait has genetic variability in Nellore cattle. The genetic
      correlations between visual scores, and SR and DC were low and favourable. The
      genetic changes in C, P and M were 0.02, 0.03 and 0.03/year, respectively. For SR
      and DC, genetic trends were 0.01/year and -0.01 days/year, respectively,
      indicating that the increase in genetic merit for reproductive traits was small
      over time. Direct selection for visual scores together with female reproductive
      traits is recommended to increase the fertility of beef cows.

PMID- 23148971
TI  - Employing a Monte Carlo algorithm in expectation maximization restricted maximum
      likelihood estimation of the linear mixed model.
AB  - Multiple-trait and random regression models have multiplied the number of
      equations needed for the estimation of variance components. To avoid inversion or
      decomposition of a large coefficient matrix, we propose estimation of variance
      components by Monte Carlo expectation maximization restricted maximum likelihood
      (MC EM REML) for multiple-trait linear mixed models. Implementation is based on
      full-model sampling for calculating the prediction error variances required for
      EM REML. Performance of the analytical and the MC EM REML algorithm was compared
      using a simulated and a field data set. For field data, results from both
      algorithms corresponded well even with one MC sample within an MC EM REML round.
      The magnitude of the standard errors of estimated prediction error variances
      depended on the formula used to calculate them and on the MC sample size within
      an MC EM REML round. Sampling variation in MC EM REML did not impair the
      convergence behaviour of the solutions compared with analytical EM REML analysis.
      A convergence criterion that takes into account the sampling variation was
      developed to monitor convergence for the MC EM REML algorithm. For the field data
      set, MC EM REML proved far superior to analytical EM REML both in computing time
      and in memory need.

PMID- 23148972
TI  - Calculation of identity-by-descent probabilities of short chromosome segments.
AB  - For some purposes, identity-by-descent (IBD) probabilities for entire chromosome
      segments are required. Making use of pedigree information, length of the segment
      and the assumption of no crossing-over, a generalization of a previously
      published graph theory oriented algorithm accounting for nonzero IBD of common
      ancestors is given, which can be viewed as method of path coefficients for entire
      chromosome segments. Furthermore, rules for setting up a gametic version of a
      segmental IBD matrix are presented. Results from the generalized graph theory
      oriented method, the gametic segmental IBD matrix and the segmental IBD matrix
      for individuals are identical.

PMID- 23148973
TI  - An assessment of linkage disequilibrium in Holstein cattle using a Bayesian
      network.
AB  - Linkage disequilibrium (LD) is defined as a non-random association of the
      distributions of alleles at different loci within a population. This association
      between loci is valuable in prediction of quantitative traits in animals and
      plants and in genome-wide association studies. A question that arises is whether
      standard metrics such as D' and r(2)  reflect complex associations in a genetic
      system properly. It seems reasonable to take the view that loci associate and
      interact together as a system or network, as opposed to in a simple pairwise
      manner. We used a Bayesian network (BN) as a representation of choice for an LD
      network. A BN is a graphical depiction of a probability distribution and can
      represent sets of conditional independencies. Moreover, it provides a visual
      display of the joint distribution of the set of random variables in question. The
      usefulness of BN for linkage disequilibrium was explored and illustrated using
      genetic marker loci found to have the strongest effects on milk protein in
      Holstein cattle based on three strategies for ranking marker effect estimates:
      posterior means, standardized posterior means and additive genetic variance. Two
      different algorithms, Tabu search (a local score-based algorithm) and incremental
      association Markov blanket (a constraint-based algorithm), coupled with the chi
      square test, were used for learning the structure of the BN and were compared
      with the reference r(2)  metric represented as an LD heat map. The BN captured
      several genetic markers associated as clusters, implying that markers are inter
      related in a complicated manner. Further, the BN detected conditionally dependent
      markers. The results confirm that LD relationships are of a multivariate nature
      and that r(2)  gives an incomplete description and understanding of LD. Use of an
      LD Bayesian network enables inferring associations between loci in a systems
      framework and provides a more accurate picture of LD than that resulting from the
      use of pairwise metrics.

PMID- 23148974
TI  - Selection strategies for dairy buffaloes: economic and genetic consequences.
AB  - Buffaloes are generally raised in Brazil without milk-recording programs, and
      thus without genetic evaluations of any of their traits. This study evaluated the
      economic impacts of three different selection strategies on buffalo populations
      and the evolution of genetic trends, genetic variances and inbreeding
      coefficients resulting from each of them. The selection strategies used were as
      follows: (i) random selection; (ii) phenotypic selection; and (iii) progeny
      testing (PT). As the numbers of herds enrolled in milk-recording programs
      increased, phenotypic selection and PT strategies increased both monetary
      benefits and genetic trends. The extra costs of implementing milk recording (MR)
      and PT procedures were exceeded by the income resulting from better buffalo
      performance. Progeny testing is known to result in beneficial genetic trends and
      the use of artificial insemination promoted better distributions of genetic
      material into herds that were not enrolled in milk-recording programs. Phenotypic
      selection and PT increased mean milk production--a key factor in profitability.
      Inbreeding levels remained stable with phenotypic selection, even as the numbers
      of MR herds increased. Increases in the numbers of sires that were evaluated
      reduced the mean inbreeding coefficient in PT. Increasing the number of herds
      enrolled in milk-recording programs resulted in increased numbers of sires needed
      for PT, but this did not increase the inbreeding coefficient. In summary,
      phenotypic selection and PT strategies appear to be economically viable for
      buffalo husbandry in south-eastern Brazil under current (2007-2008) economic
      conditions and should be encouraged.

PMID- 23148976
TI  - Neural stimulation for visual rehabilitation: advances and challenges.
AB  - Blindness affects tens of million people worldwide and its prevalence constantly
      increases along with population aging. In some pathologies leading to vision
      loss, prosthetic approaches are currently the only hope for the patient to
      recover some visual perception. Here, we review the latest advances in visual
      prosthetic strategies with their respective strength and weakness. The principle
      is to electrically stimulate neurons along the visual pathway. Ocular approaches
      target the remaining retinal cells whereas brain stimulation aims at stimulating
      higher visual structures directly. Even though ocular approaches are less
      invasive and easier to implement, brain stimulation can be applied to diseases
      where the connection between the retina and the brain is lost such as in glaucoma
      and could therefore benefit to patients with different pathologies. Today,
      numbers of groups are investigating these strategies and the first devices start
      being commercialized. However, critical bottlenecks still impair our scientific
      efforts towards efficient visual implants. These challenges include electrode
      miniaturization, material optimization, multiplexing of stimulation channels and
      encoding of visual information into electrical stimuli. 

PMID- 23148977
TI  - Working older, a challenge for the future.

PMID- 23148978
TI  - Depression among parents of children with disabilities.
AB  - We examined the rate of depression among 110 parents of children with
      disabilities and tested a model to determine the unique factors associated with
      parental depression. Consenting parents completed measures of depression, family
      satisfaction, physical health, problem-solving abilities, stress appraisals, and
      child functional impairment. Participants were categorized as depressed or
      nondepressed based on their responses to the Patient Health Questionnaire (PHQ9;
      Kroenke, Spitzer, & Williams, 2001). Nineteen percent of the parents met
      screening criteria for depression. Regression analyses revealed that threat
      appraisals, poorer physical health, and lower family satisfaction were uniquely
      associated with depression status with 83.3% accuracy. These findings highlight
      the importance of family satisfaction, problem solving ability, physical health,
      and the influence of appraisal processes on depression among parents of children
      with disabilities.

PMID- 23148979
TI  - Stress spillover of health symptoms from healthy spouses to patient spouses in
      older married couples managing both diabetes and osteoarthritis.
AB  - Many studies examining illness within marriage have investigated how illness in
      one spouse influences the other spouse. In later-life marriages, where both
      spouses are more likely to have health challenges, there is an increased
      likelihood that health symptoms from both spouses affect each other. In the
      current study we examined how health symptoms in a "healthy" spouse may
      exacerbate health problems in a partner (the patient) who is managing multiple
      chronic illnesses. Surveys were collected across 14 days from 27 later-life
      couples where patients had both diabetes and osteoarthritis. Results indicated
      that higher healthy spouse symptoms were generally associated with higher patient
      symptoms, suggesting a spillover effect. Spouse reports of positive and negative
      mood were inversely linked with patient health outcomes. Spouse reports of higher
      positive marital interactions were surprisingly linked with higher patients'
      arthritis activity and activity limitations, possibly indicating a compensatory
      effect where marital interactions increase with symptoms. Daily spouse reports of
      positive marital interactions and mood were linked with patient health outcomes
      even after the spillover of health symptoms was taken into account.

PMID- 23148981
TI  - Promoting self-management in diabetes: efficacy of a collaborative care approach.
AB  - Diabetes is a leading cause of death and is estimated to cost the United States
      90 billion dollars annually. Increasing patient self-management skills has been
      shown to improve outcomes in patients with Type II diabetes. Promotion of shared
      decision-making between patient and provider is a core element of collaborative
      care and is especially well suited for increasing patient self-management.
      Research trials to date have been limited in demonstrating how self-management
      promotion can be fully integrated into primary care practices. Demonstration of
      the impact of this approach is needed. This study involves 22 randomly assigned
      physicians across three family medicine clinics to either provide usual care or
      work with a part-time collaborative care therapist in their clinic serving as an
      outreach health coach for their diabetic patients. Each outreach health coach met
      with each physician in the intervention group to identify patients most in need
      of intervention, sent identified patients a video on diabetes management, and
      called to encourage video viewing and discuss any patient-perceived barriers to
      self-management. Initial markers of patient activation in self-management,
      patients' video-viewing behavior, and health care encounters in the subsequent 6
      months were compared between groups. Results showed that patients targeted by an
      outreach health coach were more likely to view the video, be seen by their
      primary care physician (PCP) within 6 months, and have disease-relevant
      laboratory tests performed than patients receiving usual care from their PCP (p <
      .05). This approach, linking PCPs with collaborative care staff, is viewed as
      expanding the engagement of PCPs with the collaborative team for superior patient
      health outcomes.

PMID- 23148980
TI  - The individual and combined influence of the "quality" and "quantity" of family
      meals on adult body mass index.
AB  - Although there is a well-established literature showing a positive association
      between the frequency of family meals and child and adolescent healthful dietary
      intake and lower body mass index (BMI), little is known about the association
      between family meal frequency (quantity) and adult health outcomes and whether
      quality (distractions) of family meals influences adult BMI. This study
      investigates the association between the quantity and quality of family meals and
      adult BMI. Data were from a nationally representative sample of 4,885 adults ages
      25 to 64 years (56% female), from which an analytic sample of 1,779 parents was
      drawn for the current study. Multiple linear regression was used to test the
      relationship between family meal frequency and quality of family meals and adult
      BMI, controlling for sociodemographics. Interactions between family meal quantity
      and quality were also examined. The quantity of family meals and the quality of
      family meals were both independently related to adult BMI. Specifically, the
      frequency of family meals was associated with lower adult BMI and lower quality
      of family meals was associated with higher adult BMI. The interaction between
      quantity and quality was not statistically significant. Results suggest that both
      the quantity and quality of family meals matter for adult BMI, but one is not
      dependent on the other. Health care providers who work with families may want to
      consider promoting the importance of the quality and quantity of family meals to
      benefit the entire family.

PMID- 23148983
TI  - Effect of GBR12909 on affective behavior: distinguishing motivational behavior
      from antidepressant-like and addiction-like behavior using the runway model of
      intracranial self-stimulation.
AB  - RATIONALE: It was recently demonstrated that the priming stimulation effect (PSE)
      in the runway model of intracranial self-stimulation (ICSS) can be used as a
      model system to study the motivational effects of drugs. However, the
      characteristics of this novel experimental model have not been fully clarified.
      OBJECTIVE: To elucidate the involvement of dopamine uptake inhibition in
      motivated behavior and the difference in experimental characteristics between
      closely related experimental models, we investigated the effects of the dopamine
      uptake inhibitor GBR12909 in the runway ICSS model, in the forced swimming test
      (FST), and on conditioned place preference (CPP). In addition, the role of
      dopamine receptor signaling in the runway model was evaluated using dopamine
      receptor agonists and antagonists. RESULTS: GBR12909 dose-dependently increased
      running speed on the runway and decreased immobility time in the FST without
      affecting the time spent in the drug-associated compartment in CPP tests. The
      effect of GBR12909 in the runway model was inhibited by pre-treatment with the
      dopamine receptor antagonists haloperidol and raclopride. The dopamine receptor
      agonists SKF38393 and quinpirole dose-dependently decreased running speed.
      CONCLUSIONS: These results demonstrate that GBR12909 displays motivation
      enhancing and antidepressant-like effects without place conditioning effects. In
      addition, the mechanisms of PSE enhancement in the runway ICSS model are
      different from those underlying closely associated experimental models and are
      mediated by increases in dopamine signaling.

PMID- 23148984
TI  - Predation by carabid beetles on the invasive slug Arion vulgaris in an
      agricultural semi-field experiment.
AB  - Arion vulgaris Moquin-Tandon 1855 is one of the most important invasive species
      in Europe, affecting both biodiversity and agriculture. The species is spreading
      in many parts of Europe, inflicting severe damage to horticultural plants and
      cultivated crops partly due to a lack of satisfactory and effective management
      solutions. Molluscicides have traditionally been used to manage slug densities,
      although the effects are variable and some have severe side-effects on other
      biota. Thus, there is a need to explore potential alternatives such as biological
      control. The nematode Phasmarhabditis hermaphrodita is the only biological agent
      that has been applied commercially so far. However, other biological control
      agents such as carabid beetles have also been found to be promising. In addition,
      some carabid species have been shown to feed on A. vulgaris in the field as well
      as in the laboratory. Two species in particular have been found to be important
      predators of A. vulgaris, and these species are also common in agricultural
      environments: Pterostichus melanarius and Carabus nemoralis. This study is the
      first to use semi-field experiments in a strawberry field, manipulating
      densities, to investigate how P. melanarius and C. nemoralis affect densities of
      A. vulgaris eggs and juveniles, respectively. Gut contents of C. nemoralis were
      analysed using multiplex PCR methods to detect DNA of juvenile slugs. Results
      show that both P. melanarius and C. nemoralis significantly affect densities of
      slug eggs and juvenile slugs under semi-field conditions and that C. nemoralis
      seems to prefer slugs smaller than one gram. Carabus nemoralis seems to be
      especially promising in reducing densities of A. vulgaris, and future studies
      should investigate the potential of using this species as a biological control
      agent.

PMID- 23148985
TI  - Antimicrobial susceptibility and resistance mechanisms of clinical Clostridium
      difficile from a Chinese tertiary hospital.
AB  - Clostridium difficile is a predominant cause of antibiotic-associated diarrhoea.
      It is increasingly difficult to treat C. difficile infection efficiently owing to
      its multidrug resistance. In the present study, 60 clinical C. difficile isolates
      were collected and analysed for their genotype, antimicrobial susceptibility and
      resistance mechanisms. Tandem repeat sequence typing (TRST) generated 21 types,
      including the epidemic clone tr017. Antimicrobial susceptibility testing of eight
      antibiotics was performed by the agar dilution method. Rifampicin, metronidazole
      and vancomycin remained the most potent agents in vitro, whilst the resistance
      rates of other agents such as ciprofloxacin, cefoxitin, clindamycin, tetracycline
      and moxifloxacin varied from 30% to 100%. 73.33% of the strains were
      multiresistant to at least three classes of antibiotics, and tr017 strains made
      up the greatest proportion of multidrug resistance. By further investigating the
      resistance mechanisms, amino acid substitutions in target enzymes encoded by
      gyrA/gyrB and rpoB were observed in fluoroquinolone- and rifampicin-resistant
      strains, respectively. The erm(B) gene was the most prevalent in macrolide
      lincosamide-streptogramin B (MLS(B))-resistant strains, and the ErmB determinant
      'Erj2', a novel genetic organisation identified in this study, plays a central
      role in conferring resistance, especially in epidemic strains. Moreover,
      transposon Tn916 carrying the tet(M) gene is more common than Tn5397 in
      tetracycline resistance.

PMID- 23148987
TI  - Transvenous lead extractions in CRT patients: the end is only the beginning.

PMID- 23148986
TI  - Carbapenem-associated multidrug-resistant Acinetobacter baumannii are sensitised
      by aztreonam in combination with polyamines.
AB  - Carbapenem-associated multidrug-resistant Acinetobacter baumannii (MDR-Ab) are
      common among clinical isolates worldwide and are a major therapeutic challenge.
      Previously it was shown that exogenous polyamines (spermine and spermidine)
      enhanced susceptibility to beta-lactams but induced resistance to polymyxins in
      Pseudomonas aeruginosa. This study aimed to explore the possible availability of
      exogenous polyamines in treating carbapenem-associated MDR-Ab. The effects of
      polyamines on the growth rate of A. baumannii, minimum inhibitory concentrations
      (MICs) of antibiotics, and time-kill and chequerboard assays were determined.
      Roles of lipopolysaccharide (LPS) and beta-lactamase activity of A. baumannii
      were also assessed for the polyamine effects. Growth of A. baumannii was
      unaffected at 4mM spermine and 16 mM spermidine alone, but was significantly
      inhibited by a subinhibitory concentration of aztreonam (AZT) (8 MUg/mL) and
      those concentrations of the polyamines. MICs to AZT alone (>=128 MUg/mL) were
      reduced to the range 0.25-8 MUg/mL in combination with polyamines in all
      carbapenem-associated MDR-Ab. MICs to penicillins, but not to ceftazidime and
      meropenem, were also significantly reduced, whilst MICs to other antibiotics,
      including polymyxin B, were unaffected in combination with polyamines for all
      tested A. baumannii. Polyamine effects on AZT were strongly synergistic with
      bactericidal activity and were retained at concentrations of 5mM MgCl(2) (or
      CaCl(2)) or 200 mM NaCl. Roles of LPS and beta-lactamase in the polyamine effects
      were excluded. Overall results suggest that AZT in combination with polyamines
      may be useful for the treatment of carbapenem-associated MDR-Ab.

PMID- 23148988
TI  - Efficient serum-resistant lipopolyplexes targeted to the folate receptor.
AB  - In this work, we have developed and evaluated a new targeted lipopolyplex (LPP),
      by combining polyethylenimine (PEI), 1,2-dioleoyl-3-(trimethylammonium) propane
      (DOTAP)/Chol liposomes, the plasmids pCMVLuc/pCMVIL-12, and the ligand folic acid
      (FA), able to transfect HeLa and B16-F10 cells in the presence of very high
      concentration of serum (60% FBS). These complexes (Fol-LPP) have a net positive
      surface charge. The combination of folic acid with lipopolyplexes also enhanced
      significantly the transfection activity of the therapeutic gene interleukin-12
      (IL-12), without any significant cytotoxicity. The specificity of the folate
      receptor (FR)-mediated gene transfer was corroborated by employing a folate
      receptor deficient cell line (HepG2). This formulation improved gene delivery
      showed by conventional lipoplexes or polyplexes resulting an efficient, simple,
      and nontoxic method for gene delivery of therapeutic genes in vitro and very
      probably in vivo.

PMID- 23148989
TI  - Thiolated hydroxyethyl cellulose: design and in vitro evaluation of mucoadhesive
      and permeation enhancing nanoparticles.
AB  - Within this study, HEC-cysteamine nanoparticles with free thiol groups in the
      range of 117-1548 MUmol/g were designed and characterized. Nanoparticles were
      generated via ionic gelation of the cationic polymer with tripolyphosphate (TPP)
      followed by covalent crosslinking via disulfide bond formation using H2O2 as
      oxidant. The mean diameter of the particles was in the range of 270-360 nm, and
      zeta potential was determined to be +4 to +10 mV. Nanoparticles were evaluated in
      terms of mucoadhesive, permeation enhancing, and biocompatible properties as well
      as biodegradability. The particles remained attached to porcine intestinal mucosa
      up to 70% after 3h of incubation. The more nanoparticles were oxidized; however,
      the less were their mucoadhesive properties. Nanoparticles applied in a
      concentration of 0.5% (m/v) with the highest content of free thiol groups
      improved the transport of fluorescein isothiocyanate dextran 4 (FD4) across Caco
      2 cell monolayer 3.94-fold in comparison with control (buffer). In addition, the
      transport of FD4 was even 1.84-fold enhanced in the presence of 0.5% (m/v)
      nanoparticles with the lowest free thiol group content. The higher the disulfide
      bond content within nanoparticles was, to a lower degree nanoparticles were
      hydrolyzed by cellulase. None of these nanoparticles showed pronounced
      cytotoxicity. Accordingly, HEC-cysteamine could be a promising excipient for
      nanoparticulate delivery systems for poorly absorbed drugs.

PMID- 23148990
TI  - Distinct functions of erythropoietin and stem cell factor are linked to
      activation of mTOR kinase signaling pathway in human erythroid progenitors.
AB  - Erythropoietin (EPO) and Stem Cell Factor (SCF) have partially distinct functions
      in erythroid cell development. The primary functions of EPO are to prevent
      apoptosis and promote differentiation, with a minor role as a mitogen. On the
      other hand SCF acts primarily as a mitogenic factor promoting erythroid cell
      proliferation with a minor role in inhibition of apoptosis. The concerted effects
      of these two growth factors are responsible for guiding initial commitment,
      expansion and differentiation of progenitors. The aim of the study was to
      identify signaling elements pertinent to translational control and elucidate
      whether both cytokines can contribute to protein translation providing some
      functional redundancy as seen with respect to apoptosis. The current study
      focused on non-apoptotic functions of SCF mediated through mTOR/p70S6 leading to
      protein translation and cell proliferation. We utilized a human primary erythroid
      progenitors and erythroblasts that are responsive to EPO and SCF to investigate
      the activation of mTOR/p70S6 kinases and their downstream effectors, the pathway
      primarily responsible for protein translation. We showed that mTOR, p70S6 kinases
      and their downstream signaling elements 4EBP1 and S6 ribosomal protein are all
      activated by SCF but not by EPO in primary erythroid progenitors. We also found
      that SCF is the sole contributor to activation of the protein translational
      machinery and activation of mTOR/p70S6 pathway is confined to the proliferative
      phase of erythroid differentiation program. Altogether these results demonstrate
      that unlike the survival function which is supported by both EPO and SCF protein
      translation essential for proliferation is governed by only SCF.

PMID- 23148991
TI  - Association analysis of single nucleotide polymorphisms of proinflammatory
      cytokine and their receptors genes with rheumatoid arthritis in northwest Chinese
      Han population.
AB  - OBJECTIVE: To analyze the relationship of genetic polymorphisms in IL1beta, IL6,
      TNF-alpha genes and their receptors genes with rheumatoid arthritis (RA) for
      northwest Han Chinese. This study also explores whether there are gene-gene
      interactions among these genetic polymorphisms. METHODS: A total of 452 patients
      with RA and 373 matched healthy controls were enrolled to carry out a case
      control study for 16 SNPs of IL1B-511 C>T, IL1B-31 T>C, IL1B+3954 C>T, IL1RN T>C,
      IL6-597 G>A, IL6-572 G>C, IL6-174 G>C, IL6R-183 G>A, IL6R exon2 T>A, IL6R exon1
      A>C, TNFA-863 C>A, TNFA-857 C>T, TNFA-308 G>A, TNFA-238 G>A, TNFR1-383 A>C and
      TNFR2 T676G T>G from seven genes. Genotyping for the SNPs was conducted on the
      RotorGene 6000 PCR platform using in-house high resolution melting (HRM)
      approaches. Detection correctness was validated through direct sequencing.
      Generalized multifactor dimensionality reduction (GMDR) analysis was applied to
      discover likely gene-gene interaction model among the SNPs. RESULTS: The results
      showed that the genotype distributions of TNFA-308, TNFA-857 and TNFA-863 are
      significantly different between case and control groups (P=0.016, P=0.048 and
      P=0.016, respectively). Carriers of TNFA-857 mutant allele conferred risk to RA
      (OR=1.525, 95% CI=1.157-2.009) while those of TNFA-308 and TNFA-863 mutant
      alleles conferred protection to RA (OR=0.459, 95% CI=0.286-0.739; OR=0.490, 95%
      CI=0.329-0.732). GMDR analysis for the SNPs indicated that gene-gene interaction
      existed among IL1B-31, IL1RN, IL6-572, IL6R-183, IL6R-exon1 and TNFA-857.
      Thirteen of all genotypes of the six SNPs combination were discovered to have
      significant distribution difference between RA group and the control.
      CONCLUSIONS: This study demonstrated that PCR-HRM assay is a highly efficient SNP
      genotyping method especially for the detection of large-scale samples. The SNPs
      of TNFA-308 and TNFA-863 are closely associated with RA susceptibility and that
      gene-gene interactions may occur among the six SNPs of IL1B-31, IL1RN, IL6-572,
      IL6R-183, IL6R-exon1 and TNFA-857 in RA patients from northwest Chinese Han
      population, especially these SNPs' combination genotypes CT/TT/CC/GG/AC/CC,
      CT/TT/GC/AA/AC/CT and CT/CT/CC/GA/AC/CC to show high risk of RA susceptibility in
      our study.

PMID- 23148993
TI  - Ingested (oral) thyrotropin releasing factor (TRH) inhibits EAE.
AB  - BACKGROUND: Ingested immunoactive proteins type I IFN, SIRS peptide 1-21, alpha
      MSH, ACTH, SST inhibit clinical attacks and inflammation in acute EAE by
      decreasing Th1-like cytokines, increasing Th2-like cytokines or increasing T(reg)
      cell frequencies. OBJECTIVE: We examined whether another protein, thyrotropin
      releasing factor (TRH), would have similar anti-inflammatory effects in EAE after
      oral administration. DESIGN/METHODS: B6 mice were immunized with MOG peptide 35
      55 and gavaged with control saline or TRH during ongoing disease. Splenocytes
      from mock fed or TRH fed mice were adoptively transferred into active MOG peptide
      35-55 immunized recipient mice during ongoing disease. RESULTS: Ingested (oral)
      TRH inhibited ongoing disease and decreased inflammation. Adoptively transferred
      cells from TRH fed donors protected against actively induced disease and
      decreased inflammation. In actively fed mice, oral TRH decreased IL-17 and TNF
      alpha cytokines in both the spleen and the CNS. In recipients of donor cells from
      TRH fed mice there was a reduction of Th1 and Th17 and induction of Th2-like IL
      13 cytokines in both the spleen and CNS. Oral TRH decreased clinical score and
      decreased inflammatory foci in both actively fed and recipients of actively fed
      mice. There was no significant increase in T(reg) cell frequencies in actively
      fed or recipients of TRH fed donor cells. CONCLUSIONS: Ingested (orally
      administered) TRH can inhibit clinical disease, inhibit CNS inflammation by
      decreasing Th1-like, Th17 and TNF-alpha cytokines and increasing Th2-like
      cytokines (IL-13) in the CNS.

PMID- 23148992
TI  - Systemic inflammation associated with mechanical ventilation among extremely
      preterm infants.
AB  - Little evidence is available to document that mechanical ventilation is an
      antecedent of systemic inflammation in preterm humans. We obtained blood on
      postnatal day 14 from 726 infants born before the 28th week of gestation and
      measured the concentrations of 25 inflammation-related proteins. We created
      multivariable models to assess the relationship between duration of ventilation
      and protein concentrations in the top quartile. Compared to newborns ventilated
      for fewer than 7 days (N=247), those ventilated for 14 days (N=330) were more
      likely to have elevated blood concentrations of pro-inflammatory cytokines (IL
      1beta, TNF-alpha), chemokines (IL-8, MCP-1), an adhesion molecule (ICAM-1), and a
      matrix metalloprotease (MMP-9), and less likely to have elevated blood
      concentrations of two chemokines (RANTES, MIP-1beta), a matrix metalloproteinase
      (MMP-1), and a growth factor (VEGF). Newborns ventilated for 7-13 days (N=149)
      had systemic inflammation that approximated the pattern of newborns ventilated
      for 14 days. These relationships were not confounded by chorioamnionitis or
      antenatal corticosteroid exposure, and were not altered appreciably among infants
      with and without bacteremia. These findings suggest that 2 weeks of ventilation
      are more likely than shorter durations of ventilation to be accompanied by high
      blood concentrations of pro-inflammatory proteins indicative of systemic
      inflammation, and by low concentrations of proteins that might protect from
      inflammation-mediated organ injury.

PMID- 23148994
TI  - Simple and rapid detection method for the mutations in SLC22A12 that cause
      hypouricemia by allele-specific real-time polymerase chain reaction.
AB  - BACKGROUND: Hypouricemia is a disorder that serum urate level is less than 2.0
      mg/dl, and relatively common in the Japanese population, where the main genetic
      cause of hypouricemia is W258X and R90H mutations in human urate trasnsporter
      1(SLC22A12). Small scale screening has relied on time-consuming traditional ways
      like polymerase chain reaction-restriction fragment length polymorphism (PCR
      RFLP). Therefore, it is beneficial that we have an easy and rapid detection
      method for these mutations. METHODS: In this report, we established a touchdown
      allele-specific real-time polymerase chain reaction (ASPCR) assay for detecting
      W258X and R90H mutations in SLC22A12, respectively. RESULTS: Quantifiable
      discrimination was successfully achieved by ?Ct value. Furthermore, we conducted
      W258X and R90H screening against 120 control genome sets, whereby frequency was
      2.92% for W258X, and not detected for R90H, respectively. CONCLUSIONS: The two
      mutations, W258X and R90H in SLC22A12 were successfully genotyped by an easy and
      rapid ASPCR assay.

PMID- 23148995
TI  - Epidemiology and genotype distribution of human papillomavirus (HPV) in women of
      Henan Province, China.
AB  - BACKGROUND: Human papillomavirus (HPV) infection is the commonest sexually
      transmitted infection, which is associated with various clinical conditions. This
      study aimed to determine the distribution of HPV genotypes in the women of Henan
      Province, China. METHODS: Cervical samples were collected by liquid-based method
      and consecutively evaluated cervical cytology and the presence of HPV DNA.
      Cytological classification was made according to the Bethesda 2001 criteria. HPV
      DNA was tested with xMAP technology by Luminex200TM. RESULTS: In cervical
      abnormalities, the infection rate of HPV was 84.0%, single type was 71.0%,
      multiple type was 13.0%, high risk HPV was 78.0% and low risk HPV was 8.0%. The
      most common genotypes found were HPV16, 52, 58, 33, 18, 6 and 39. The most common
      HPV genotypes were HPV16, 52, 6, 58 and 33 in NILM, HPV16, 52, 18, 58 and 6 in
      ASCUS, HPV52, 16, 58, 6 and 39 in LSIL, HPV16, 33, 58, 18 and 51 in HSIL, and
      HPV16, 18, 33, 58 and 52 in ICC, respectively. The prevalence of single HPV and
      multiple HPV was 64.8% and 13.3%, respectively. Age-specific prevalence of
      multiple HPV exhibited a "U" shaped curve. CONCLUSIONS: Single HPV genotype
      infection was predominantly detected in different groups of cervical lesions in
      Henan Province, and HPV16, 52, 58, 33, 18 and 6 were the priority HPV types.

PMID- 23148996
TI  - Robust controller design for fuzzy parametric uncertain systems: an optimal
      control approach.
AB  - A new approach of designing a robust controller for fuzzy parametric uncertain
      systems is proposed. A linear time invariant (LTI) system with fuzzy coefficients
      is called as fuzzy parametric uncertain system (FPUS). The proposed method
      envisages conversion of the FPUS into an uncertain (interval) state space
      controllable canonical form system in terms of its alpha cut. Further, the
      problem of designing a robust controller is translated into an optimal control
      problem minimizing a cost function. For matched uncertainty, it is shown that the
      optimal control problem is a linear quadratic regulator (LQR) problem, which can
      be solved to obtain a robust controller for FPUS. The numerical examples and
      simulation results show the effectiveness of the proposed method in terms of
      robustness of the controller.

PMID- 23148998
TI  - Coronary computed tomography angiography for stable angina: past, present, and
      future.
AB  - Although the clinical use of computed tomography in cardiac imaging had slow
      beginnings, it has seen rapid development over the past decade. This review aims
      to discuss the state of the technology and to help clarify its role in the
      diagnosis and management of coronary artery disease. This article highlights
      major historic perspectives, the accuracy of coronary computed tomography
      angiography in evaluating obstructive coronary artery disease, associated
      radiation exposure issues, considerations in patient selection, and ongoing
      clinical and technologic advancements.

PMID- 23148997
TI  - Optimize radiochemotherapy in pancreatic cancer: PARP inhibitors a new
      therapeutic opportunity.
AB  - Cancer cells may use PARP enzymes and Homologous Recombination to repair single
      and double strand breaks caused by genotoxic insults. In this study, the PARP-1
      inhibitor Rucaparib was utilized to increase the sensitivity to chemoradiotherapy
      treatment in BRCA-2-deficient and -proficient pancreatic cancer cells. We used
      the pancreatic cancer cell lines, Capan-1 with mutated BRCA-2 and Panc-1, AsPC-1
      and MiaPaCa-2 with BRCA-1/2 wild type. Cells were treated with Rucaparib and/or
      radiotherapy (4-10 Gy) plus Gemcitabine then the capability to proliferate was
      evaluated by colony formation, cell counting and MTT assays. Flow cytometry,
      immunocytochemistry and western blotting were utilized to assess cell response to
      Rucaparib plus irradiation. The antitumour effectiveness of combining the PARP-1
      inhibitor before, together and after radiotherapy evidenced the first as the
      optimal schedule in blocking cell growth. Pre-exposure to Rucaparib increased the
      cytotoxicity of Gemcitabine plus radiotherapy by heavily inducing the
      accumulation of cells in G2/M phase, impairing mitosis and finally inducing
      apoptosis and authophagy. The upregulation of p-Akt and downregulation of p53
      were evidenced in MiaPaCa-2 which displayed replication stress features. For the
      first time, the rationale of using a PARP inhibitor as chemoradiosensitizer in
      pancreatic cancer models has been hypothesized and demonstrated.

PMID- 23148999
TI  - Percutaneous intrapericardial injection of triamcinolone in a patient with
      incessant pericarditis: a novel technique.
AB  - Incessant pericarditis is an uncommonly encountered clinical problem that can be
      extremely difficult to manage. We present a case of incessant pericarditis with
      multiple recurrences during tapering of systemic corticosteroids. We injected
      intrapericardial triamcinolone, using a technique originally developed to access
      the epicardium for catheter ablation. This approach resulted in immediate
      success, followed by long-term resolution of the patient's pericarditis. This
      novel technique may be of benefit in this small group of patients and may
      represent a safer alternative to pericardiectomy for those resistant to oral
      corticosteroid tapering.

PMID- 23149000
TI  - Prevalence and distribution of coronary artery calcification in asymptomatic
      British population.

PMID- 23149001
TI  - Arguments against the biomarker-driven diagnosis of AD.

PMID- 23149002
TI  - [Complete wrist denervation: a retrospective study of 27 cases with a mean follow
      up period of 77 months].
AB  - OBJECTIVES: Complete wrist denervation is a palliative operation, which yields
      still controversial outcomes. The aim of our study is to assess the late outcomes
      of complete wrist denervation. METHODS: In a retrospective continuous review of
      27 complete and isolated denervations of the wrist joint performed by the same
      surgeon in 27 patients (15 men for 12 women) from 1995 to 2007, the pain (VAS),
      the function (Dash-score), the range of motion, the strength (Jamar) and the
      radiological changes were assessed at a mean follow-up period of 77 months (12 to
      157). RESULTS: At final follow-up, 12 patients (44%) were completely free of pain
      and 11 (41%) had little pain, four (15%) had moderate and severe pain. The
      average time to achieve the complete pain relief was 3 months and 3 weeks. Pain
      relief was stable over time in 89% of cases. There was a significant improvement
      in range of motion: 11 degrees  flexion/extension; 8 degrees  pronosupination. In
      average, the Jamar grip strength was 85% of the healthy side. The Dash-score was
      in average 30.4 (22 to 60). The extension of the osteoarthritic surface was
      observed in 14 patients (52%). Six complications were noted: one complex regional
      pain syndrome, five neuromas four of which resolved spontaneously. Two patients
      were re-operated. Eighteen patients were very satisfied (67%), six patients were
      satisfied (22%) and three patients were moderately satisfied (11%). CONCLUSIONS:
      Complete wrist denervation is an intervention with few complications indicated in
      chronic wrist pain of any aetiology.

PMID- 23149003
TI  - [Anterior dislocation of the elbow joint without peri-articular fracture in an
      adult].
AB  - In view of the comparative frequency of posterior dislocations of the elbow, it
      is rather remarkable that anterior dislocations of that joint should be among the
      rarest of injuries [1]. Our case is one of the first cases of anterior
      dislocation of the elbow without any periarticular fracture or pre-existing
      deformities around the elbow [2].

PMID- 23149004
TI  - Progressive cribriform and zosteriform hyperpigmentation.

PMID- 23149005
TI  - Subclinical cardiotoxicity detected by strain rate imaging up to 14 months after
      breast radiation therapy.
AB  - PURPOSE: Strain rate imaging (SRI) is a new echocardiographic modality that
      enables accurate measurement of regional myocardial function. We investigated the
      role of SRI and troponin I (TnI) in the detection of subclinical radiation
      therapy (RT)-induced cardiotoxicity in breast cancer patients. METHODS AND
      MATERIALS: This study prospectively included 75 women (51 left-sided and 24 right
      sided) receiving adjuvant RT to the breast/chest wall and regional lymph nodes.
      Sequential echocardiographs with SRI were obtained before RT, immediately after
      RT, and 8 and 14 months after RT. TnI levels were measured on the first and last
      day of RT. RESULTS: Mean heart and left ventricle (LV) doses were both 9 +/- 4 Gy
      for the left-sided patients and 4 +/- 4 Gy and 1 +/- 0.4 Gy, respectively, for
      the right-sided patients. A decrease in strain was observed at all post-RT time
      points for left-sided patients (-17.5% +/- 1.9% immediately after RT, -16.6% +/-
      1.4% at 8 months, and -17.7% +/- 1.9% at 14 months vs -19.4% +/- 2.4% before RT,
      P<.01) but not for right-sided patients. When we considered left-sided patients
      only, the highest mean dose was given to the anterior left ventricular (LV) wall
      (25 +/- 14 Gy) and the lowest to the inferior LV wall (3 +/- 3 Gy). Strain of the
      anterior wall was reduced after RT (-16.6% +/- 2.3% immediately after RT, -16% +/
      2.6% at 8 months, and -16.8% +/- 3% at 14 months vs -19% +/- 3.5% before RT,
      P<.05), whereas strain of the inferior wall showed no significant change. No
      changes were observed with conventional echocardiography. Furthermore, mean TnI
      levels for the left-sided patients were significantly elevated after RT compared
      with before RT, whereas TnI levels of the right-sided patients remained
      unaffected. CONCLUSIONS: In contrast to conventional echocardiography, SRI
      detected a regional, subclinical decline in cardiac function up to 14 months
      after breast RT. It remains to be determined whether these changes are related to
      clinical outcome. In the meantime, we encourage the use of radiation techniques
      that minimize the exposure of the anterior LV wall in left-sided patients.

PMID- 23149006
TI  - The need for more evidence-based studies to justify the economic value for the
      provision of medication therapy management and other clinical pharmacy services.

PMID- 23149007
TI  - Stability of an alternative extemporaneous captopril fast-dispersing tablet
      formulation versus an extemporaneous oral liquid formulation.
AB  - BACKGROUND: Administration of medications to pediatric patients is challenging
      because many drugs are not commercially available in appropriate dosage
      formulations and/or strengths. Consequently, these drugs are prepared
      extemporaneously as oral liquid (OL) formulations using marketed tablets or
      capsules. In many cases, the stability of these extemporaneous preparations,
      which may affect their tolerability, has not been documented. An alternative
      extemporaneous solid formulation, such as a fast-dispersing tablet (FDT), may
      offer enhanced stability as well as dosing flexibility because it may be
      administered as an orodispersible tablet or as a reconstituted
      suspension/solution. Although FDTs are available increasingly as patient-friendly
      oral dosage formulations, and their simple method of manufacture can be applied
      to extemporaneous formulations, such applications have not been explored to date.
      OBJECTIVES: The use of extemporaneous captopril OL formulations in hospitals in
      Ireland was surveyed, and the stability of the most commonly used captopril
      formulation (reference) was investigated and compared with that of a newly
      available extemporaneous FDT formulation. METHODS: The survey was carried out in
      120 hospitals in the Republic of Ireland. The 56-day stability of the most
      commonly used formulation was compared with that of a newly available
      extemporaneous captopril FDT preparation. The captopril content of the
      formulations was measured by high-performance liquid chromatography analysis.
      Formulations were also monitored for changes in appearance, including color;
      odor; and pH (OLs only). RESULTS: The survey showed that extemporaneously
      prepared captopril OLs were extensively used, particularly in specialist
      children's hospitals. The most commonly used preparation was a xanthan gum-based
      oral suspension. Analysis of these OL preparations showed the OLs to have been
      stable up to day 7, but that the captopril concentration decreased to 72% to 84%
      at day 14 and to 59% to 68% at day 56; this decrease was accompanied by a pungent
      odor suggestive of captopril oxidation. In contrast, FDT formulations
      demonstrated greater stability, with 96% of captopril present at day 56.
      CONCLUSIONS: The results of this study support only a 7-day stability for the
      currently dispensed captopril OL in hospitals in Ireland. In contrast, a
      stability of at least 56 days was shown with the FDTs. The FDTs may represent an
      alternative and convenient oral solid extemporaneous preparation of captopril
      and, potentially, other extemporaneous pediatric medications.

PMID- 23149008
TI  - Eunice Kennedy Shriver National Institute of Child Health and Human Development
      Pediatrics Formulation Initiative: proceedings from the Second Workshop on
      Pediatric Formulations.
AB  - BACKGROUND: The Eunice Kennedy Shriver National Institute of Child Health and
      Human Development of the National Institutes of Health (NIH) organized a workshop
      held in November 2011 to address knowledge gaps that limit the availability of
      adequate pediatric formulations. This workshop was used as a means to identify
      the types of research innovations needed and to stimulate research efforts
      designed to improve the availability of pediatric formulations and the
      technologies required to make these formulations. METHODS: Information for this
      article was gathered from the proceedings of the Second US PFI Workshop sponsored
      by the Eunice Kennedy Shriver National Institute of Child Health and Human
      Development in Bethesda, Maryland, on November 1 and 2, 2011, as well as from
      post-workshop discussions. The workshop preparation began with formation of 4
      working groups: Biopharmaceutics, Biopharmaceutics Classification System (BCS),
      New Technology and Drug Delivery Systems, and Taste and Flavor. RESULTS: The
      recommendations of the 4 working groups will form the basis for the development
      of a blueprint to guide future research efforts. The pediatric-specific problems
      identified include the heterogeneity of the population, the small size of the
      pediatric drug market, the limited number of new formulations for the large
      number of off-patent and unlabeled drugs, and the lack of universal agreement on
      how to define appropriate formulations for different ages and stages of
      development. There was consensus on the need to develop a universal technology
      platform for flexible pediatric dosage forms, transforming an empirical process
      into a science-based platform. A number of problems affect the availability of
      drugs in the developing world. Age-appropriate solid oral pediatric medicines for
      common diseases can have a global impact. Success on a global scale depends on
      the commitment of policy makers, regulators, scientists, pharmaceutical
      companies, sponsors, government, and research foundations to address gaps in
      knowledge and solve public health issues related to the availability of
      formulations in the developing world. CONCLUSIONS: Solutions to the worldwide
      lack of appropriate pediatric formulations will require the development of a road
      map and the commitment of policy makers, regulators, scientists, pharmaceutical
      sponsors, academic institutions, governments, and research foundations. The
      development of a universal, cost-effective platform using existing or developing
      innovative technology that produces flexible pediatric dosage forms remains an
      important but elusive goal.

PMID- 23149009
TI  - Summary of the National Institute of Child Health and Human Development-best
      pharmaceuticals for Children Act Pediatric Formulation Initiatives Workshop
      Pediatric Biopharmaceutics Classification System Working Group.
AB  - BACKGROUND: The Biopharmaceutics Classification System (BCS) allows compounds to
      be classified based on their in vitro solubility and intestinal permeability. The
      BCS has found widespread use in the pharmaceutical community to be an enabling
      guide for the rational selection of compounds, formulation for clinical
      advancement, and generic biowaivers. The Pediatric Biopharmaceutics
      Classification System (PBCS) Working Group was convened to consider the
      possibility of developing an analogous pediatric-based classification system.
      Because there are distinct developmental differences that can alter intestinal
      contents, volumes, permeability, and potentially biorelevant solubilities at
      different ages, the PBCS Working Group focused on identifying age-specific issues
      that need to be considered in establishing a flexible, yet rigorous PBCS.
      OBJECTIVE: We summarized the findings of the PBCS Working Group and provided
      insights into considerations required for the development of a PBCS. METHODS:
      Through several meetings conducted both at The Eunice Kennedy Shriver National
      Institute of Child Health, Human Development-US Pediatric Formulation Initiative
      Workshop (November 2011) and via teleconferences, the PBCS Working Group
      considered several high-level questions that were raised to frame the
      classification system. In addition, the PBCS Working Group identified a number of
      knowledge gaps that need to be addressed to develop a rigorous PBCS. RESULTS: It
      was determined that for a PBCS to be truly meaningful, it needs to be broken down
      into several different age groups that account for developmental changes in
      intestinal permeability, luminal contents, and gastrointestinal (GI) transit.
      Several critical knowledge gaps were identified, including (1) a lack of fully
      understanding the ontogeny of drug metabolizing enzymes and transporters along
      the GI tract, in the liver, and in the kidney; (2) an incomplete understanding of
      age-based changes in the GI, liver, and kidney physiology; (3) a clear need to
      better understand age-based intestinal permeability and fraction absorbed
      required to develop the PBCS; (4) a clear need for the development and
      organization of pediatric tissue biobanks to serve as a source for ontogenic
      research; and (5) a lack of literature published in age-based pediatric
      pharmacokinetics to build physiologically- and population-based pharmacokinetic
      (PBPK) databases. CONCLUSIONS: To begin the process of establishing a PBPK model,
      10 pediatric therapeutic agents were selected (based on their adult BCS
      classifications). These agents should be targeted for additional research in the
      future. The PBCS Working Group also identified several areas where greater
      emphasis on research was needed to enable the development of a PBCS.

PMID- 23149010
TI  - Materials to clinical devices: technologies for remotely triggered drug delivery.
AB  - BACKGROUND: Technologies in which a remote trigger is used to release drug from
      an implanted or injected device could enable on-demand release profiles that
      enhance therapeutic effectiveness or reduce systemic toxicity. A number of new
      materials have been developed that exhibit sensitivity to light, ultrasound, or
      electrical or magnetic fields. Delivery systems that incorporate these materials
      might be triggered externally by the patient, parent or physician to provide
      flexible control of dose magnitude and timing. OBJECTIVES: To review injectable
      or implantable systems that are candidates for translation to the clinic, or ones
      that have already undergone clinical trials. Also considered are applicability in
      pediatrics and prospects for the future of drug delivery systems. METHODS: We
      performed literature searches of the PubMed and Science Citation Index databases
      for articles in English that reported triggerable drug delivery devices, and for
      articles reporting related materials and concepts. RESULTS: Approaches to
      remotely-triggered systems that have clinical potential were identified. Ideally,
      these systems have been engineered to exhibit controlled on-state release
      kinetics, low baseline leak rates, and reproducible dosing across multiple
      cycles. CONCLUSIONS: Advances in remotely-triggered drug delivery have been
      brought about by the convergence of numerous scientific and engineering
      disciplines, and this convergence is likely to play an important part in the
      current trend to develop systems that provide more than one therapeutic modality.
      Preclinical systems must be carefully assessed for biocompatibility, and
      engineered to ensure pharmacokinetics within the therapeutic window. Future drug
      delivery systems may incorporate additional modalities, such as closed-loop
      sensing or onboard power generation, enabling more sophisticated drug delivery
      regimens.

PMID- 23149011
TI  - Delivery of inhaled drugs for infants and small children: a commentary on present
      and future needs.
AB  - Although the manufacture of inhaled medications is a multibillion dollar
      industry, virtually no pharmaceutical drug/device combination has been approved
      for inhalation across the range of pediatric patient ages and sizes. The
      clinician who treats neonates, infants, or toddlers is often faced with the
      dilemma of prescribing inhaled medications that may be disease appropriate but
      have not been approved for use in patients in these age categories. Their use is
      thus technically "off label," with limited empirical data to guide both dose and
      device selection. This dilemma requires the prescribing physician to go beyond
      the limitations of the product label, often without benefit of appropriately
      designed clinical trials, in an attempt to select safe and effective doses for
      use with these smallest of patients. The vast majority of drugs approved for
      inhalation were studied by using aerosol devices designed for older children and
      adults using a mouthpiece interface, which may not be practical for use in
      infants and patients aged <4 years. The selection of the most age-appropriate
      device and interface is critical for the effective administration of the
      prescribed therapy. In the absence of industry-sponsored clinical trials in
      neonates, infants, and toddlers, in vitro and in vivo strategies may help guide
      age-appropriate dosing, device, and interface selection to better inform clinical
      practice. In this commentary, the challenges in developing and prescribing
      effective formulations for aerosol delivery across the range of pediatric ages
      and sizes are explored, with guidance for device and interface selection.
      Recommendations for future collaborative sharing of in vitro models and age
      specific breathing patterns between academic and industry researchers could help
      regulators and clinicians better understand the impact age and size have on
      pulmonary drug delivery.

PMID- 23149013
TI  - Dual ionic interaction system based on polyelectrolyte complex and ionic,
      injectable, and thermosensitive hydrogel for sustained release of human growth
      hormone.
AB  - A dual ionic interaction system composed of a positively charged polyelectrolyte
      complex (PEC) containing human growth hormone (hGH) and anionic thermosensitive
      hydrogel has been suggested for sustained delivery of bioactive hGH. The PEC was
      prepared by ionic interaction between negatively charged hGH and positively
      charged protamine sulfate (PS) to suppress diffusion of hGH. Moreover, we loaded
      the positively charged PEC into an anionic, injectable, and thermosensitive
      poly(organophosphazene) hydrogel to enhance sustained release of hGH by dual
      ionic interactions. PS formed a spherical complex with hGH, and their ionic
      interaction grew stronger with increasing amounts of PS. From a weight ratio of
      0.5, the PS/hGH complex had a size and zeta-potential that were constantly
      maintained around 500 nm and +8 mV, respectively, in 0.9% NaCl. The PEC-loaded
      hydrogels suppressed the initial burst release of hGH and extended the release
      period in vitro and in vivo. In a pharmacokinetic study in rats, the PEC-loaded
      anionic hydrogel extended half-life 13-fold with similar area under the curve
      (AUC) compared to hGH solution. Furthermore, single injection of PEC-loaded
      anionic hydrogel showed a more increased growth rate than daily injection of hGH
      solution for 7 days in hypophysectomized rats, demonstrating its potential as an
      injectable, sustained delivery system that can release bioactive hGH.

PMID- 23149012
TI  - Understanding the host response to cell-laden poly(ethylene glycol)-based
      hydrogels.
AB  - Poly(ethylene glycol) (PEG)-based hydrogels are promising in situ cell carriers
      for tissue engineering. However, their success in vivo will in part depend upon
      the foreign body reaction (FBR). This study tests the hypothesis that the FBR
      affects cells encapsulated within PEG hydrogels, and in turn influences the
      severity of the FBR. Fibroblasts were encapsulated within PEG hydrogels
      containing RGD to support cell attachment. Macrophages were seeded on top of cell
      laden hydrogels to mimic in vivo macrophage interrogation and treated with
      lipopolysaccharide to induce an inflammatory phenotype. The presence of activated
      macrophages reduced fibroblast gene expression for extracellular matrix molecules
      and remodeling, but stimulated VEGF and IL-1beta gene expression. Fibroblasts
      impacted macrophage phenotype leading to increased iNOS, IL-1beta and TNF-alpha
      expressions. Syngeneic cell-laden and acellular hydrogels were also implanted
      subcutaneously into C57bl/6 mice for 2, 7 and 28 days. Encapsulated fibroblasts
      secreted collagen type I during the first week, but tissue deposition and
      cellularity decreased by 28 days. The presence of encapsulated fibroblasts led to
      greater acute inflammation, but did not influence the fibrotic response. In
      summary, this work emphasizes the importance of the host response in tissue
      engineering, and the potentially deleterious impact it may have on cell-laden
      synthetic scaffolds.

PMID- 23149015
TI  - Effect of Wolbachia on insecticide susceptibility in lines of Aedes aegypti.
AB  - Two stable infections of Wolbachia pipientis, wMelPop and wMel, now established
      in Aedes aegypti, are being used in a biocontrol program to suppress the
      transmission of dengue. Any effects of Wolbachia infection on insecticide
      resistance of mosquitoes may undermine the success of this program. Bioassays of
      Ae. aegypti were conducted to test for differences in response to insecticides
      between Wolbachia infected (wMelPop, wMel) and uninfected lines. Insecticides
      screened were bifenthrin, the pyrethroid commonly used for adult knockdown, as
      well as larvicides: Bacillus thuringiensis var. israelensis, the organophosphate,
      temephos and the insect growth regulator, s-methoprene. While differences in
      response between lines were detected for some insecticides, no obvious or
      consistent effects related to presence of Wolbachia infection were observed.
      Spreading Wolbachia infections are, therefore, unlikely to affect the efficacy of
      traditional chemical control of mosquito outbreaks.

PMID- 23149016
TI  - Collagen XVI in health and disease.
AB  - Collagen XVI, by structural analogy a member of the FACIT- (fibril-associated
      collagens with interrupted triple helices) family of collagens, is described as a
      minor collagen component of connective tissues. Collagen XVI is expressed in
      various cells and tissues without known occurrence of splice variants or
      isoforms. For skin and cartilage tissues its suprastructure is known. Presumably,
      there it acts as an adaptor protein connecting and organizing large fibrillar
      networks and thus modulates integrity and stability of the extracellular matrix
      (ECM). Collagen XVI is produced by myofibroblasts in the normal intestine and its
      synthesis is increased in the inflamed bowel wall where myofibroblasts develop
      increased numbers of focal adhesion contacts on collagen XVI. Consequently,
      recruitment of alpha1 integrin into the focal adhesions at the tip of the cells
      is induced followed by increased cell spreading on collagen XVI. This presumably
      adds to the maintenance of myofibroblasts in the inflamed intestinal regions and
      thus promotes fibrotic responses of the tissue. Notably, alpha1/alpha2 integrins
      interact with collagen XVI through an alpha1/alpha2beta1 integrin binding site
      located in the COL 1-3 domains. Collagen XVI may act as a substrate for adhesion
      and invasion of connective tissue tumor cells. In glioblastoma it induces tumor
      invasiveness by modification of the beta1-integrin activation pattern. Thus,
      altering the cell-matrix interaction through collagen XVI might be a molecular
      mechanism to further augment the invasive phenotype of glioma cells. In this
      line, in oral squamous cell carcinoma collagen XVI expression is induced which
      results in an upregulation of Kindlin-1 followed by an increased interaction with
      beta1-integrin. Consequently, collagen XVI induces a proliferative tumor
      phenotype by promoting an early S-phase entry. In summary, collagen XVI plays a
      decisive role in the interaction of connective tissue cells with their ECM, which
      is impaired in pathological situations. Alteration of tissue location and
      expression level of collagen XVI appears to promote tumorigenesis and to
      perpetuate inflammatory reactions.

PMID- 23149017
TI  - Analyzing titers of antibodies against bacterial and viral antigens, and
      bacterial toxoids in the intravenous immunoglobulins utilized in Taiwan.
AB  - Intravenous immunoglobulin (IVIG) manufactured from human plasma contains IgG as
      the primary ingredient, and is used for indications such as immunodeficiency
      syndrome. Available IVIGs in Taiwan are either manufactured from Taiwanese or
      North American plasma. The effectiveness of the national immunization program of
      Taiwan can be evaluated by analyzing and comparing IVIG antibody titers that are
      induced through the corresponding vaccines (tetanus, diphtheria, and pertussis,
      measles, rubella, hepatitis A, hepatitis B and varicella). Both enzyme-linked
      immunosorbent assay (ELISA) and the in vitro neutralization test demonstrated
      that all IVIGs provide adequate clinical protection against diphtheria and
      tetanus toxins. ELISA results further revealed that plasma of Taiwanese subjects
      contains higher levels of pertussis toxin and filamentous hemagglutinin
      antibodies, when compared to foreign IVIGs. This may be related to the later
      adoption of acellular pertussis vaccine in Taiwan. Antibodies titers against
      measles, rubella, hepatitis A, and varicella-zoster virus were otherwise low. Low
      titers of hepatitis B surface antigen antibodies are present in Taiwanese plasma
      IVIG, indicating immune memory decline or loss. In conclusion, our results show
      that Taiwanese IVIG contains varying titers of vaccine-induced antibodies, and
      serves as a guide for future amendments to Taiwan's immunization program.

PMID- 23149014
TI  - Zinc finger function of HIV-1 nucleocapsid protein is required for removal of 5'
      terminal genomic RNA fragments: a paradigm for RNA removal reactions in HIV-1
      reverse transcription.
AB  - During (-) strong-stop DNA [(-) SSDNA] synthesis, RNase H cleavage of genomic
      viral RNA generates small 5'-terminal RNA fragments (14-18 nt) that remain
      annealed to the DNA. Unless these fragments are removed, the minus-strand
      transfer reaction, required for (-) SSDNA elongation, cannot occur. Here, we
      describe the mechanism of 5'-terminal RNA removal and the roles of HIV-1
      nucleocapsid protein (NC) and RNase H cleavage in this process. Using an NC
      dependent system that models minus-strand transfer, we show that the presence of
      short terminal fragments pre-annealed to (-) SSDNA has no impact on strand
      transfer, implying efficient fragment removal. Moreover, in reactions with an
      RNase H(-) reverse transcriptase mutant, NC alone is able to facilitate fragment
      removal, albeit less efficiently than in the presence of both RNase H activity
      and NC. Results obtained from novel electrophoretic gel mobility shift and
      Forster Resonance Energy Transfer assays, which each directly measure RNA
      fragment release from a duplex in the absence of DNA synthesis, demonstrate for
      the first time that the architectural integrity of NC's zinc finger (ZF) domains
      is absolutely required for this reaction. This suggests that NC's helix
      destabilizing activity (associated with the ZFs) facilitates strand exchange
      through the displacement of these short terminal RNAs by the longer 3' acceptor
      RNA, which forms a more stable duplex with (-) SSDNA. Taken together with
      previously published results, we conclude that NC-mediated fragment removal is
      linked mechanistically with selection of the correct primer for plus-strand DNA
      synthesis and tRNA removal step prior to plus-strand transfer. Thus, HIV-1 has
      evolved a single mechanism for these RNA removal reactions that are critical for
      successful reverse transcription.

PMID- 23149018
TI  - Biomechanical analysis of surface-athlete impacts on third-generation artificial
      turf.
AB  - BACKGROUND: Excessive repetitive loads are widely believed to be the cause of
      overload or overuse injuries. On third-generation artificial turf, impacts have
      been found to vary with surface and shoe properties. Mechanical devices are
      considered not representative for measuring impact absorption during athletic
      movements, and pressure insoles have been shown as inaccurate with regard to
      magnitude of force. PURPOSE: To compare impact properties between different third
      generation artificial turf systems in combination with various cleat
      configurations in vivo using force plate technology. STUDY DESIGN: Controlled
      laboratory study. METHODS: Twenty-two male soccer players (mean +/- SD: age, 23.1
      +/- 2.8 y; height, 1.81 +/- 0.1 m; body mass, 77.5 +/- 6.0 kg) performed 10 short
      sprints, 5 straight with a sudden stop and 5 with a 90 degrees  cut, over a force
      plate covered with artificial turf for each combination of 3 turf systems and 3
      cleat configurations. RESULTS: During stop sprints, peak impact was significantly
      higher on a recreational-level turf system than professional-level turf systems
      with and without an underlying shock pad (3.12 body weight [W] vs 3.01 W and 3.02
      W, respectively). During cut sprints, peak impact was significantly higher with
      traditional round cleats than with turf cleats and bladed cleats (2.99 W vs 2.84
      W and 2.87 W, respectively). CONCLUSION: The results indicate that both an
      increase in assumed impact-absorbing surface properties and a larger distribution
      of shorter cleats produced lower impacts during standardized athletic movements.
      Regardless, none of the shoe-surface combinations yielded peak impacts of an
      assumed hazardous magnitude. CLINICAL RELEVANCE: The study provides information
      on the extent to which various third-generation artificial turf systems and cleat
      configurations affect impact force, widely believed to be a causative factor for
      overload and overuse injuries.

PMID- 23149019
TI  - The effect of arthroscopic partial medial meniscectomy on tibiofemoral stability.
AB  - BACKGROUND: There is still little known regarding the effects of meniscus
      resection size on tibiofemoral stability. PURPOSE: To determine if partial medial
      meniscectomy of the posterior horn significantly alters tibiofemoral stability as
      measured by the anterior-posterior (AP) position and laxity of the medial femoral
      condyle. STUDY DESIGN: Controlled laboratory study. METHODS: Five cadaveric knees
      were dissected to the capsule, preserving all ligaments and the quadriceps
      tendon. Each specimen was first tested on a rig where the AP position and laxity
      of the medial femoral condyle were measured while a range of forces was applied
      from full extension to 90 degrees  of flexion. Magnetic resonance imaging (MRI)
      at 3 tesla was then performed for baseline measurements of the meniscus before
      partial meniscectomy. Arthroscopic partial medial meniscectomy aimed at 30% of
      the posterior horn was then performed, followed by repeat mechanical testing and
      MRI. The sequence was then repeated for arthroscopic partial meniscectomy aimed
      at 60% and 100% of the posterior horn of the medial meniscus. RESULTS: The MRI
      analysis demonstrated that 22% +/- 9% of the original width of the posterior horn
      was removed at the first resection, 46% +/- 11% was removed at the second
      resection, and the third resection was 100% removal of the posterior horn for all
      specimens. After 22% resection, no significant difference in AP laxity was
      observed. A statistically significant increase in AP laxity was observed with 46%
      resection under a 500-N compressive load compared with the intact meniscus. After
      full resection, significant increases in AP laxity were observed under a 50-N
      compressive load compared with the intact and 22% and 46% resections. The 22%
      resection had similar AP positions as the intact knee, whereas the 46% resection
      and 100% removal of the posterior horn had statistically further posterior AP
      positions than the intact knee. CONCLUSION: Partial medial meniscectomy with
      >=46% resection of the original width of the posterior horn significantly altered
      the AP position of the medial femoral condyle and also increased laxity. CLINICAL
      RELEVANCE: These mechanical changes may lead to abnormal cartilage loading and
      early osteoarthritis.

PMID- 23149021
TI  - Early emotional processing deficits in depersonalization: an exploration with
      event-related potentials in an undergraduate sample.
AB  - Emotional stimuli may draw attention to such an extent that they hamper the
      processing of subsequent signals, a phenomenon termed emotion-induced blindness
      (EIB). As depersonalization is associated with self-reported attenuated emotional
      responses, the present study explored whether individuals scoring high on the
      Cambridge Depersonalization Scale (CDS; n=15) exhibit a diminished EIB effect
      relative to low CDS scoring individuals (n=15), and whether attentional processes
      reflected in event-related potentials (ERPs) are implicated in this effect. We
      obtained an EIB effect such that emotional distractors that preceded targets with
      a lag of 200ms reduced correct detection of targets. Although the magnitude of
      this effect was similar for high and low CDS participants, high CDS participants
      exhibited a significantly lower ERP amplitude at the frontal lead in the 200
      300ms window than did low CDS individuals to targets that followed emotional
      versus neutral distractors. This latter effect was significantly related to the
      Alienation factor of the CDS. This pattern suggests that difficulties in the
      discrimination between emotional and neutral stimuli relate to the feeling of
      unreality in depersonalization.

PMID- 23149022
TI  - Closed eyes condition increases auditory brain responses in schizophrenia.
AB  - The 40-Hz auditory steady-state responses (ASSRs) of 14 medicated schizophrenic
      patients were recorded in eyes-open and eyes-closed conditions as previously done
      in healthy volunteers. Patients show significantly increased precision of the
      evoked response with eyes closed, and a significant increase of broad-band noise
      activity when eyes are open.

PMID- 23149020
TI  - Three-dimensional mapping of hippocampal and amygdalar structure in euthymic
      adults with bipolar disorder not treated with lithium.
AB  - Structural neuroimaging studies of the amygdala and hippocampus in bipolar
      disorder have been largely inconsistent. This may be due in part to differences
      in the proportion of subjects taking lithium or experiencing an acute mood state,
      as both factors have recently been shown to influence gray matter structure. To
      avoid these problems, we evaluated euthymic subjects not currently taking
      lithium. Thirty-two subjects with bipolar type I disorder and 32 healthy subjects
      were scanned using magnetic resonance imaging. Subcortical regions were manually
      traced, and converted to three-dimensional meshes to evaluate the main effect of
      bipolar illness on radial distance. Statistical analyses found no evidence for a
      main effect of bipolar illness in either region, although exploratory analyses
      found a significant age by diagnosis interaction in the right amygdala, as well
      as positive associations between radial distance of the left amygdala and both
      prior hospitalizations for mania and current medication status. These findings
      suggest that, when not treated with lithium or in an acute mood state, patients
      with bipolar disorder exhibit no structural abnormalities of the amygdala or
      hippocampus. Future studies, nevertheless, that further elucidate the impact of
      age, course of illness, and medication on amygdala structure in bipolar disorder
      are warranted.

PMID- 23149023
TI  - Behavioral regulation in methamphetamine abusers: an fMRI study.
AB  - The goal of this study was to extend our previous findings of abnormal prefrontal
      function in methamphetamine (MA) abusers and controls and to link the imaging
      data to behavioral, demographic and drug use variables. We used a fast event
      related functional magnetic resonance imaging (fMRI) design to examine trial-to
      trial reaction time (RT) adjustments in 30 MA abusers and 30 controls. A variant
      of the Stroop task was employed to measure influence of response conflict on RT,
      including the level of trial-to-trial RT adjustments seen after conflict trials.
      Compared to control subjects, MA abusers exhibited reduced RT adjustments and
      reduced activation in the prefrontal cortex (PFC) after conflict trials. RT
      adjustment correlated negatively with PFC brain activity in the MA group, while a
      trend for a positive correlation was observed in controls. No correlations were
      observed between task performance or brain activity and age, education or drug
      use variables. These data support our previous findings that the ability to adapt
      a behavioral response based on prior experience is compromised in MA abusers.
      Interestingly, these impairments do not appear to be linked to drug use patterns
      or to educational levels.

PMID- 23149024
TI  - A window into the invisible wound of war: functional neuroimaging of REM sleep in
      returning combat veterans with PTSD.
AB  - Relative regional cerebral metabolic rate of glucose in rapid eye movement (REM)
      sleep and wakefulness was explored in combat veterans with and without
      posttraumatic stress disorder PTSD, using positron emission tomography.
      Hypermetabolism in brain regions involved in arousal regulation, fear responses,
      and reward processing persist during REM sleep in combat veterans with PTSD.

PMID- 23149025
TI  - Diffusion tensor imaging evidence of white matter disruption associated with loss
      versus alteration of consciousness in warfighters exposed to combat in Operations
      Enduring and Iraqi Freedom.
AB  - The effects on the human brain of mild traumatic brain injury (mTBI), which is
      defined as a brief alteration (AOC) or loss of consciousness (LOC), are
      incompletely understood. Major psychiatric illnesses such as major depressive
      disorder (MDD) and posttraumatic stress disorder (PTSD) are common after mTBI.
      Prior research suggests that individuals who develop MDD after blast-related mTBI
      versus those who do not show significant white matter disruption and higher rates
      of LOC, suggesting that LOC might be uniquely associated with brain changes that
      increase the risk of developing mental illness after neurotrauma. Therefore, the
      objective of this study was to examine the effects of LOC, MDD, and PTSD on white
      matter integrity in individuals who reported experiencing mTBI during combat in
      Operations Enduring and Iraqi Freedom. We hypothesized that LOC would be
      associated with significant disruption of white matter, above and beyond putative
      effects of MDD and PTSD. To test this hypothesis, 46 individuals who experienced
      blast-related mTBI underwent a detailed clinical assessment and diffusion tensor
      imaging. As hypothesized, LOC versus AOC individuals displayed significantly
      lower fractional anisotropy (FA) in 14 regions, which included the superior
      longitudinal fasciculus and corpus callosum. No regions of significant FA
      difference were identified between individuals with and without PTSD, or between
      individuals with and without MDD. These preliminary results show that LOC is
      associated with detectable alterations in brain microstructure and may suggest a
      brain basis for psychiatric symptoms and mental illness after mTBI.

PMID- 23149026
TI  - The comparison of pre- and post-treatment (99m)Tc HMPAO brain SPECT images in
      patients with obsessive-compulsive disorder.
AB  - The objective of the present study was to compare brain activation in patients
      with obsessive-compulsive disorder (OCD) who received pharmacotherapy (selective
      serotonin reuptake inhibitor (SSRI) or a SSRI-risperidone combination) with that
      in healthy controls using (99m)Tc-hexamethyl propyleneamine oxime (HMPAO) brain
      single photon emission tomography (SPECT). Twelve OCD patients achieving clinical
      response (seven SSRI responders, five patients responded to SSRI plus
      risperidone) underwent post-treatment SPECT scan. The baseline regional cerebral
      blood flow (rCBF) was significantly reduced in a large part of the cerebral
      cortex and the left cingulate gyrus in OCD patients compared with controls. After
      a 50% reduction of the OCD symptoms, bilaterally increased rCBF in the thalamus
      showed a significant effect of time in both of the patient groups. In the
      remitted state, although rCBF in the cingulate gyrus did not differ in SSRI
      responders compared with controls, patients who responded to the combination of
      SSRI+ risperidone showed significant hypoperfusion in the left anterior cingulate
      gyrus. SSRI responders had normalized rCBF in the frontal region relative to the
      control group. Consequently, based on our results, we attribute the observed
      thalamic rCBF alteration to SSRI treatment. Our results also suggested that brain
      perfusion changes associated with clinical remission may differ across patient
      subgroups. 

PMID- 23149027
TI  - Meta-analysis based SVM classification enables accurate detection of Alzheimer's
      disease across different clinical centers using FDG-PET and MRI.
AB  - The application of support vector machine classification (SVM) to combined
      information from magnetic resonance imaging (MRI) and [F18]fluorodeoxyglucose
      positron emission tomography (FDG-PET) has been shown to improve detection and
      differentiation of Alzheimer's disease dementia (AD) and frontotemporal lobar
      degeneration. To validate this approach for the most frequent dementia syndrome
      AD, and to test its applicability to multicenter data, we randomly extracted FDG
      PET and MRI data of 28 AD patients and 28 healthy control subjects from the
      database provided by the Alzheimer's Disease Neuroimaging Initiative (ADNI) and
      compared them to data of 21 patients with AD and 13 control subjects from our own
      Leipzig cohort. SVM classification using combined volume-of-interest information
      from FDG-PET and MRI based on comprehensive quantitative meta-analyses
      investigating dementia syndromes revealed a higher discrimination accuracy in
      comparison to single modality classification. For the ADNI dataset accuracy rates
      of up to 88% and for the Leipzig cohort of up to 100% were obtained. Classifiers
      trained on the ADNI data discriminated the Leipzig cohorts with an accuracy of
      91%. In conclusion, our results suggest SVM classification based on quantitative
      meta-analyses of multicenter data as a valid method for individual AD diagnosis.
      Furthermore, combining imaging information from MRI and FDG-PET might
      substantially improve the accuracy of AD diagnosis.

PMID- 23149029
TI  - Impaired pre-attentive change detection in major depressive disorder patients
      revealed by auditory mismatch negativity.
AB  - Patients with major depressive disorder (MDD) show deficits in cognitive
      functions. However, the neural mechanisms underlying the pre-attentive
      information processing in MDD patients are poorly understood. The present study
      investigated whether MDD patients have impairments in pre-attentive information
      processing indexed by auditory mismatch negativity (MMN). The deviant-standard
      reverse oddball paradigm was used to obtain the memory-comparison-based duration
      auditory MMN in 24 MDD patients and 24 healthy control subjects. Over the frontal
      central area, MDD patients exhibited decreased MMN amplitudes only for the
      increment condition (150-ms MMN), whereas the temporal MMN did not differ between
      MDD patients and healthy subjects, regardless of the increment or decrement (50
      ms MMN) condition. The MMN amplitudes were not correlated with depression
      symptoms. In addition, the peak latency of MMN amplitudes was longer in the MDD
      patients than the control subjects. These data indicate that pre-attentive
      information processing is impaired in MDD patients. This dysfunction may
      represent a trait of MDD patients rather than a state-dependent phenomenon.

PMID- 23149030
TI  - Predicting dementia development in Parkinson's disease using Bayesian network
      classifiers.
AB  - Parkinson's disease (PD) has broadly been associated with mild cognitive
      impairment (PDMCI) and dementia (PDD). Researchers have studied surrogate,
      neuroanatomic biomarkers provided by magnetic resonance imaging (MRI) that may
      help in the early diagnosis of this condition. In this article, four
      classification models (naive Bayes, multivariate filter-based naive Bayes, filter
      selective naive Bayes and support vector machines, SVM) have been applied to
      evaluate their capacity to discriminate between cognitively intact patients with
      Parkinson's disease (PDCI), PDMCI and PDD. For this purpose, the MRI studies of
      45 subjects (16 PDCI, 15 PDMCI and 14 PDD) were acquired and post-processed with
      Freesurfer, obtaining 112 variables (volumes of subcortical structures and
      thickness of cortical parcels) per subject. A multivariate filter-based naive
      Bayes model was found to be the best classifier, having the highest cross
      validated sensitivity, specificity and accuracy. Additionally, the most relevant
      variables related to dementia in PD, as predicted by our classifiers, were
      cerebral white matter, and volumes of the lateral ventricles and hippocampi. 

PMID- 23149031
TI  - Effects of alcohol dependence on cortical thickness as determined by magnetic
      resonance imaging.
AB  - Alterations of brain structures have been seen in patients suffering from drug
      abuse or mental disorders like schizophrenia. Similar changes in volume of brain
      structures have been observed in both alcoholic men and women. We examined the
      thickness of gray matter in the cerebral cortex in control men and women (n=69,
      47 men) and alcohol-dependent subjects (n=130, 83 men) to test the hypothesis
      that alcoholic inpatients would have more cortical damage than controls. We also
      hypothesized that alcoholic women would be more affected than alcoholic men.
      Alcoholic participants with a history of schizophrenia, psychotic, or bipolar
      disorder were excluded from the study. Volumetric structural magnetic resonance
      images were collected, 3D surfaces were created using Freesurfer, and statistical
      testing for cortical thickness differences was carried out using AFNI/SUMA.
      Covarying for age and years of education, we confirmed significant differences
      between alcoholics and healthy controls in cortical thickness in both the left
      and right hemispheres. Significant differences in cortical thickness between
      control men and women were also observed. These differences may reflect sexual
      dimorphisms in the human brain, a genetic predisposition to alcoholism and
      comorbid drug use, and the extent of gray matter damage in alcoholism and
      substance use.

PMID- 23149028
TI  - White matter microstructural alterations in children with prenatal
      methamphetamine/polydrug exposure.
AB  - Little is known about the effects of prenatal methamphetamine exposure on white
      matter microstructure, and the impact of concomitant alcohol exposure. Diffusion
      tensor imaging and neurocognitive testing were performed on 21 children with
      prenatal methamphetamine exposure (age 9.8+/-1.8 years; 17 also exposed to
      alcohol), 19 children with prenatal alcohol but not methamphetamine exposure (age
      10.8+/-2.3 years) and 27 typically developing children (age 10.3+/-3.3 years).
      Whole-brain maps of fractional anisotropy (FA) were evaluated using tract-based
      spatial statistics. Relative to unexposed controls, children with prenatal
      methamphetamine exposure demonstrated higher FA mainly in left-sided regions,
      including the left anterior corona radiata (LCR) and corticospinal tract Post-hoc
      analyses of these FA differences showed they likely result more from lower radial
      diffusivity (RD) than higher axial diffusivity (AD). Relative to the
      methamphetamine-exposed group, children with prenatal alcohol exposure showed
      lower FA in frontotemporal regions-particularly, the right external capsule. We
      failed to find any group-performance interaction (on tests of executive
      functioning and visuomotor integration) in predicting FA; however, FA in the
      right external capsule was significantly associated with performance on a test of
      visuomotor integration across groups. This report demonstrates unique diffusion
      abnormalities in children with prenatal methamphetamine/polydrug exposure that
      are distinct from those associated with alcohol exposure alone, and illustrates
      that these abnormalities in brain microstructure are persistent into childhood
      and adolescence--long after the polydrug exposure in utero.

PMID- 23149032
TI  - Impaired integrity of the brain parenchyma in non-geriatric patients with major
      depressive disorder revealed by diffusion tensor imaging.
AB  - Diffusion tensor imaging (DTI) is considered to be able to non-invasively
      quantify white matter integrity. This study aimed to use DTI to evaluate white
      matter integrity in non-geriatric patients with major depressive disorder (MDD)
      who were free of antidepressant medication. DTI was performed on 19 non-geriatric
      patients with MDD, free of antidepressant medication, and 19 age-matched healthy
      subjects. Voxel-based and histogram analyses were used to compare fractional
      anisotropy (FA) and mean diffusivity (MD) values between the two groups, using
      two-sample t tests. The abnormal DTI indices, if any, were tested for correlation
      with disease duration and severity, using Pearson product-moment correlation
      analysis. Voxel-based analysis showed clusters with FA decrease at the bilateral
      frontal white matter, anterior limbs of internal capsule, cerebellum, left
      putamen and right thalamus of the patients. Histogram analysis revealed lower
      peak position of FA histograms in the patients. FA values of the abnormal
      clusters and peak positions of FA histograms of the patients exhibited moderate
      correlation with disease duration and severity. These results suggest the
      implication of frontal-subcortical circuits and cerebellum in MDD, and the
      potential utility of FA in evaluation of brain parenchymal integrity.

PMID- 23149033
TI  - White matter integrity in hair-pulling disorder (trichotillomania).
AB  - Hair-pulling disorder (trichotillomania, HPD) is a disabling condition that is
      characterized by repetitive hair-pulling resulting in hair loss. Although there
      is evidence of structural grey matter abnormalities in HPD, there is a paucity of
      data on white matter integrity. The aim of this study was to explore white matter
      integrity using diffusion tensor imaging (DTI) in subjects with HPD and healthy
      controls. Sixteen adult female subjects with HPD and 13 healthy female controls
      underwent DTI. Hair-pulling symptom severity, anxiety and depressive symptoms
      were also assessed. Tract-based spatial statistics were used to analyze data on
      fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD) and
      radial diffusivity (RD). There were no differences in DTI measures between HPD
      subjects and healthy controls. However, there were significant associations of
      increased MD in white matter tracts of the fronto-striatal-thalamic pathway with
      longer HPD duration and increased HPD severity. Our findings suggest that white
      matter integrity in fronto-striatal-thalamic pathways in HPD is related to
      symptom duration and severity. The molecular basis of measures of white matter
      integrity in HPD deserves further exploration.

PMID- 23149034
TI  - More vulnerability of left than right hippocampal damage in right-handed patients
      with post-traumatic stress disorder.
AB  - Previous studies have shown hippocampal abnormalities in people with post
      traumatic stress disorder (PTSD), but findings of diminished volume in shortages
      in the hippocampus have been inconsistent. In this study, we investigated changes
      in hippocampal volume and neuronal metabolites in right-handed PTSD patients to
      determine their possible relationship(s) with PTSD severity. We performed a case
      control study of 11 right-handed PTSD patients and 11 healthy controls using
      magnetic resonance imaging (MRI) and proton magnetic resonance spectroscopy ((1)H
      MRS). Hippocampal volume and metabolite ratios of N-acetylaspartate (NAA) to
      creatine (Cr) (NAA/Cr) and choline compounds (Cho) to Cr (Cho/Cr) were
      calculated. The severity of PTSD was evaluated by the Clinician-Administered PTSD
      Scale (CAPS). Significantly decreased left and total normalized hippocampal
      volumes were found in PTSD patients compared with controls (6.6% for the left
      hippocampus, 5.5% for total hippocampus). Also, the bilateral hippocampal NAA/Cr
      ratio of PTSD patients was significantly reduced compared with controls. The
      volume of the left hippocampus was negatively correlated to the CAPS total and
      CPAS-C scores. The left hippocampal NAA/Cr ratio was negatively correlated to the
      CAPS-total, CAPS-B, CAPS-C, and CAPS-D scores. The CAPS total and the CAPS-B
      scores were positively correlated to the Cho/Cr ratio of the right hippocampus.
      Our results indicate that hippocampal dysfunction is asymmetric in right-handed
      PTSD patients, with the left side affected more than the right.

PMID- 23149035
TI  - Association study of serotonin transporter availability and SLC6A4 gene
      polymorphisms in patients with major depression.
AB  - The serotonin transporter (SERT) is hypothesized to be an important component of
      the pathophysiology of major depression (MD). The aim of this study was to use
      [(123)I]ADAM single-photon emission computed tomography (SPECT) to explore
      whether SERT availability in four regions of the brain (striatum, thalamus,
      midbrain and pons) is different in patients with MD and healthy individuals. The
      effects of three genetic variants (rs25531, rs6354 and STin2) of the serotonin
      transporter gene (SLC6A4) on SERT availability were also investigated. This study
      included 40 MD patients and 12 controls. The mean specific uptake ratio (SUR)
      values in the thalamus differed significantly between MD patients and controls.
      Genetic variants of SLC6A4, age, gender, severity of depression, and smoking
      behavior did not influence SERT availability. SERT availability might be a useful
      biomarker of the development of MD; however, a larger sample size is needed to
      provide more concrete evidence.

PMID- 23149037
TI  - Structural and functional cortical disconnection in Alzheimer's disease: a
      combined study using diffusion tensor imaging and transcranial magnetic
      stimulation.
AB  - We investigated the functional consequences of compromised white matter integrity
      in Alzheimer's disease by combining Diffusion Tensor Imaging (DTI) and
      Transcranial Magnetic Stimulation (TMS) in 19 patients with AD (Alzheimer's
      disease) and 19 healthy controls. We used a region of interest approach and
      correlated the ipsilateral silent period (iSP) and the resting motor threshold
      (RMT) from TMS with fractional anisotropy (FA) and mean diffusivity (MD) values
      of the corpus callosum and corticospinal tract. AD patients showed significant
      reductions of FA in intracortical projecting fibre tracts compared to controls
      and widespread increases in MD. TMS data showed increased latency of iSP in AD
      patients and a decreased RMT, indicating decreased motor cortical inhibition.
      Although both TMS and DTI metrics were prominently altered in AD patients,
      impaired white matter integrity was not associated with increased iSP latency or
      reduced RMT, as correlation of TMS parameters with FA and MD values in the a
      priori defined regions showed no significant effects. Therefore, we argue that
      beside the direct degeneration of the underlying fibre tracts, other
      pathophysiological mechanisms may account for the observation of decreased
      transcallosal inhibition and increased motor excitability in AD.

PMID- 23149036
TI  - Altered brain function underlying verbal memory encoding and retrieval in
      psychotic major depression.
AB  - Psychotic major depression (PMD) is associated with deficits in verbal memory as
      well as other cognitive impairments. This study investigated brain function in
      individuals with PMD during a verbal declarative memory task. Participants
      included 16 subjects with PMD, 15 subjects with non-psychotic major depression
      (NPMD) and 16 healthy controls (HC). Functional magnetic resonance imaging (fMRI)
      data were acquired while subjects performed verbal memory encoding and retrieval
      tasks. During the explicit encoding task, subjects semantically categorized words
      as either "man-made" or "not man-made." For the retrieval task, subjects
      identified whether words had been presented during the encoding task. Functional
      MRI data were processed using SPM5 and a group by condition ANOVA. Clusters of
      activation showing either a significant main effect of group or an interaction of
      group by condition were further examined using t-tests to identify group
      differences. During the encoding task, the PMD group showed lower hippocampus,
      insula, and prefrontal activation compared to HC. During the retrieval task, the
      PMD group showed lower recognition accuracy and higher prefrontal and parietal
      cortex activation compared to both HC and NPMD groups. Verbal retrieval deficits
      in PMD may be associated with deficient hippocampus function during encoding.
      Increased brain activation during retrieval may reflect an attempt to compensate
      for encoding deficits.

PMID- 23149039
TI  - Effect of magnetic seizure therapy on regional brain glucose metabolism in major
      depression.
AB  - Currently electroconvulsive therapy (ECT) is one of the only available therapies
      for treatment resistant depression (TRD). While effective, ECT is complicated by
      side effects, including cognitive impairment. One promising potential alternative
      is magnetic seizure therapy (MST). To date, no research has explored the effects
      of 100Hz MST on brain activity or the brain changes associated with response to
      treatment. Therefore the aim of this study was to determine the effects of a
      treatment course of 100Hz MST on regional brain glucose metabolism. Ten patients
      with treatment resistant depression underwent positron emission tomography with
      fluorodeoxyglucose before and after a treatment course of MST. Changes in the
      relative metabolic rate of a priori brain regions were investigated. Areas of
      increased relative metabolism after treatment were seen in the basal ganglia,
      orbitofrontal cortex, medial frontal cortex and dorsolateral prefrontal cortex. A
      secondary analysis showed trend-level differential findings in brain activation
      between responders and non-responders, namely in the ventral anterior cingulate.
      These results primarily indicate that MST is affecting regions consistent with
      the limbic-cortical dysregulation model of depression. Exploratory analysis
      indicated some differential findings in brain activation between responders and
      non-responders were also evident; however, the small sample size precludes any
      firm conclusions.

PMID- 23149038
TI  - Thalamic shape and connectivity abnormalities in children with attention
      deficit/hyperactivity disorder.
AB  - Attention-deficit/hyperactivity disorder (ADHD) is characterized by widespread
      structural and functional abnormalities in the cortico-striato-thalmo-cortical
      (CSTC) loops that subserve attention and executive functions. In this study, we
      analyzed thalamic shape and its white matter connections using structural
      magnetic resonance imaging and diffusion (DTI) data acquired from children with
      ADHD (n=19) and controls (n=19). Shape morphology of the thalamus was assessed
      using shape-based analysis, while connectivity between the thalamus and other
      brain regions was determined using probabilistic diffusion tractography. Shape
      based analysis indicated significant regional atrophy in the left thalamus in
      children with ADHD compared to controls. Group analyses of white matter
      connectivity measures showed significantly decreased mean fractional anisotropy
      (FA) and volume of the tracts between thalamus and striatum, hippocampus, and
      prefrontal lobe in children with ADHD compared to controls. The structural
      abnormalities within the thalamus and the reduced integrity of the white matter
      tracks between the thalamus and other brain regions, as shown from the results of
      this study, may be the anatomical bases of the impaired cognitive performances in
      the attention and executive function domains in ADHD.

PMID- 23149042
TI  - Improved corpus callosum area measurements by analysis of adjoining parasagittal
      slices.
AB  - The corpus callosum (CC) is a bundle of approximately 180 million axons
      connecting homologous areas of the left and right cerebral cortex. Because CC
      projections are topographically organized, regional CC morphological
      abnormalities may reflect regional cortical developmental abnormalities. We
      assess the variance characteristics of three CC area measurement techniques by
      comparing a single midsagittal slice versus three slices (midsagittal plus one
      parasagittal on each side) and five slices (midsagittal plus two parasagittal on
      each side). CC images were partitioned into five subregions using the Hofer-Frahm
      scheme under the three methods and variance was examined via two complementary
      data sets. In the first, to control for intersubject variability, 12 scans were
      acquired from a single subject over the course of 3 h. In the second, we used
      scans from 56 healthy male volunteers between the ages of 10 and 27 years
      (mean=17.47, S.D.=3.42). Increasing the number of slices from one to three to
      five diminished the coefficient of variation (CV) within subregions and increased
      the power to detect differences between groups. A power analysis was conducted
      for the sample under each method to determine the sample size necessary to
      discern a given percent change (delta) ranging from 1 to 20% iteratively.

PMID- 23149041
TI  - Feasibility of studying brain morphology in major depressive disorder with
      structural magnetic resonance imaging and clinical data from the electronic
      medical record: a pilot study.
AB  - For certain research questions related to long-term outcomes or to rare
      disorders, designing prospective studies is impractical or prohibitively
      expensive. Such studies could instead utilize clinical and magnetic resonance
      imaging data (MRI) collected as part of routine clinical care, stored in the
      electronic medical record (EMR). Using major depressive disorder (MDD) as a
      disease model, we examined the feasibility of studying brain morphology and
      associations with remission using clinical and MRI data exclusively drawn from
      the EMR. Advanced automated tools were used to select MDD patients and controls
      from the EMR who had brain MRI data, but no diagnosed brain pathology. MDD
      patients were further assessed for remission status by review of clinical charts.
      Twenty MDD patients (eight full-remitters, six partial-remitters, and six non
      remitters), and 15 healthy control subjects met all study criteria for advanced
      morphometric analyses. Compared to controls, MDD patients had significantly
      smaller right rostral-anterior cingulate volume, and level of non-remission was
      associated with smaller left hippocampus and left rostral-middle frontal gyrus
      volume. The use of EMR data for psychiatric research may provide a timely and
      cost-effective approach with the potential to generate large study samples
      reflective of the real population with the illness studied.

PMID- 23149040
TI  - Visual event-related potentials as markers of hyperarousal in Gulf War illness:
      evidence against a stress-related etiology.
AB  - An exaggerated response to emotional stimuli is among the many symptoms widely
      reported by veterans of the 1991 Persian Gulf War. These symptomologies have been
      attributed to damage and dysfunction associated with deployment-related
      exposures. We collected event-related potential data from 22 veterans meeting
      Haley criteria for Gulf War (GW) Syndromes 1-3 and from 8 matched GW veteran
      controls, who were deployed but not symptomatic, while they performed a visual
      three-condition oddball task where images authenticated to be associated with the
      1991 Persian Gulf War were the distractor stimuli. Hyperarousal reported by ill
      veterans was significantly greater than that by control veterans, but this was
      not paralleled by higher amplitude P3a in their ERP responses to GW-related
      distractor stimuli. Whereas previous studies of PTSD patients have shown higher
      amplitude P3b responses to target stimuli that are placed amid trauma-related
      nontarget stimuli, ill veterans in this study showed P3b amplitudes to target
      stimuli - placed amid GW-related nontarget stimuli - that were significantly
      lower than those of the control group. Hyperarousal scores reliably predicted
      P3b, but not P3a, amplitudes. Although many factors may contribute to P3b
      amplitude differences - most notably depression and poor sleep quality, symptoms
      that are prevalent in the GW syndrome groups - our findings in context of
      previous studies on this population are consistent with the contention that
      dysfunction in cholinergic and dopaminergic neurotransmitter systems, and in
      white matter and basal ganglia may be contributing to impairments in GW veterans.

PMID- 23149043
TI  - mGluR1/5 receptor densities in the brains of alcoholic subjects: a whole
      hemisphere autoradiography study.
AB  - Increased glutamatergic neurotransmission and hyper-excitability during alcoholic
      withdrawal and abstinence are associated with increased risk for relapse, in
      addition to compensatory changes in the glutamatergic system during chronic
      alcohol intake. Type 5 metabotropic glutamate receptor (mGlur5) is abundant in
      brain regions known to be involved in drug reinforcement, yet very little has
      been published on mGluR1/5 expression in alcoholics. We evaluated the densities
      of mGluR1/5 binding in the hippocampus and striatum of post-mortem human brains
      by using [(3)H]Quisqualic acid as a radioligand in whole hemispheric
      autoradiography of Cloninger type 1 (n=9) and 2 (n=8) alcoholics and healthy
      controls (n=10). We observed a 30-40% higher mGluR1/5 binding density in the CA2
      area of hippocampus in type 1 alcoholics when compared with either type 2
      alcoholics or healthy subjects. Although preliminary, and from a relatively small
      number of subjects from these diagnostic groups, these results suggest that the
      mGluR1/5 receptors may be increased in type 1 alcoholics in certain brain areas.

PMID- 23149044
TI  - Effects of various cryoprotectants on bull sperm quality, DNA integrity and
      oxidative stress parameters.
AB  - The objectives of this study was to compare the effects of type and concentration
      of cryoprotectants glycerol (G), ethylene glycol (EG) and dimethyl sulfoxide
      (DMSO) on the plasma membrane and DNA integrity as well as antioxidant activity
      of cryopreserved Eastern Anatolian red bull sperm. Ejaculates were collected from
      the three bulls using an artificial vagina twice a week. The ejaculates were
      pooled to increase the semen volume for replication and to eliminate variability
      among the evaluated samples. The pooled ejaculates were also split into seven
      equal experimental groups and diluted with the modified base extender to a final
      spermatozoa concentration of 15*10(6)/ml. The extended samples were cooled slowly
      to 4 degrees C and equilibrated for 4h. They were then loaded into 0.25ml French
      straws and frozen using a digital freezing machine at 3 programmed rates: -3
      degrees C/min from +4 degrees C to -10 degrees C, -40 degrees C/min from -10
      degrees C to -100 degrees C, and -20 degrees C/min from -100 degrees C to -140
      degrees C. Thereafter, the straws were plunged into liquid nitrogen at -196
      degrees C. Frozen straws were thawed individually at 37 degrees C for 30s in a
      water bath to analyse progressive motility and sperm motion characteristics as
      well as membrane integrity using hypo-osmotic swelling test. Biochemical assays
      were performed in a spectrophotometer using commercial kits. DNA damage was
      evaluated by Comet Assay using Image Analysis System. 6% G exhibited the greatest
      percentages of CASA (43.7+/-2.92%) and progressive (26.4+/-2.64%) motilities when
      compared to the other groups (P<0.001). 6% G and 6% EG showed the greatest values
      of preserved membrane integrity (P<0.001). 6% DMSO and 3% EG + 3% DMSO resulted
      in greater chromatin damage than the other groups (P<0.001). The antioxidant
      activities of GPx, GSH, and CAT as well as the total antioxidant activity were
      affected by the type of cryoprotectant; notably, 2% G+2% EG+2% DMSO yielded the
      lowest activities when compared to the other groups (P<0.001). In conclusion, no
      advantages were found in using EG or DMSO to replace G in bull sperm
      cryopreservation. Freezing with cryoprotectant 6% G yielded the best post-thaw
      sperm characteristics for Eastern Anatolian Red bull spermatozoa.

PMID- 23149045
TI  - The use of dynamic computed tomographic angiography ancillary to the diagnosis of
      brain death.
AB  - OBJECTIVE: Global absence of cerebral circulation is an important ancillary test
      for brain death when the diagnosis cannot be confirmed clinically. A number of
      imaging methods are available to assess cerebral circulation; however, new
      techniques are sought to improve on limitations of the current tests. Dynamic
      computed tomographic angiography (dCTA) is a novel technique that enables dynamic
      noninvasive imaging of cerebral blood flow. MATERIALS AND METHODS: We present the
      use of dCTA in 3 cases as a corroboratory tool to diagnose brain death. Analysis
      of our findings suggest that it is a reliable technique for demonstrating the
      lack of intracranial blood flow, with many advantages over other current methods.
      CONCLUSION: A dCTA may be used to reliably demonstrate the lack of cerebral blood
      flow in patients with suspected brain death.

PMID- 23149046
TI  - Care of people with schizophrenia suffers as too much money is spent on secure
      units.

PMID- 23149047
TI  - Nystatin-induced acute generalized exanthematous pustulosis.

PMID- 23149048
TI  - Flexural or inverse psoriasis in a patient with hidradenitis suppurativa
      receiving treatment with infliximab.

PMID- 23149049
TI  - Periorificial cutaneous tuberculosis of the vulva.

PMID- 23149050
TI  - Acquired total leukonychia in a patient with human immunodeficiency virus
      infection.

PMID- 23149051
TI  - Successful treatment of recalcitrant chronic foot eczema with alitertinoin.

PMID- 23149052
TI  - Extraocular sebaceous carcinoma: a report of 2 cases.
AB  - Sebaceous carcinoma is a rare, aggressive adnexal tumor of unknown etiology; 75%
      of these tumors arise in the periocular region while 25% arise at extraocular
      sites. This cutaneous tumor is a diagnostic sign of Muir-Torre syndrome, a
      disorder associated with visceral malignancies and gene abnormalities. Patients
      with sebaceous carcinoma should therefore be carefully evaluated; a detailed
      personal and family history of cancer, a thorough physical examination,
      additional tests where appropriate, and close monitoring will all be required. We
      report 2 cases of extraocular sebaceous carcinoma and review the literature,
      focusing on the association between sebaceous carcinoma and Muir-Torre syndrome.

PMID- 23149053
TI  - Biosynthetic porcine collagen dressings as an adjunct or definitive tool for the
      closure of scalp defects without periosteum.
AB  - BACKGROUND: Aggressive carcinomas of the scalp usually occur in elderly patients
      with multiple comorbidities. Complete excision of this type of tumor often
      involves the removal of periosteum, and the resulting defects can be difficult to
      reconstruct. OBJECTIVE: To evaluate the usefulness of porcine type I collagen
      dressings as adjunct or definitive treatment in the surgical closure of scalp
      defects without periosteum. MATERIALS AND METHODS: We performed a prospective
      study between January 2009 and November 2011 of patients with scalp defects
      larger than 5cm resulting from surgery that required the removal of periosteum to
      obtain tumor-free margins. RESULTS: The most prevalent type of tumor was
      recurrent cutaneous squamous cell carcinoma. The surgical defects ranged in
      diameter from 5 to 7cm. In 100% of the patients who received a graft after
      dressing removal (n=4), the graft took well. In the patients in whom the
      biosynthetic dressing was definitive (n=6), granulation tissue filled the defect
      and complete closure was achieved in approximately 3.5 months. CONCLUSIONS: The
      use of porcine type I collagen dressings as an adjunct or definitive tool for the
      closure of surgical defects on the scalp measuring more than 5cm in which
      periosteum has been removed proved to be simple, inexpensive, and effective.

PMID- 23149054
TI  - On cardiovascular risk estimation in patients with psoriasis: The REGICOR and
      SCORE scales.

PMID- 23149056
TI  - Testing the WHO Hand Hygiene Self-Assessment Framework for usability and
      reliability.
AB  - BACKGROUND: The World Health Organization (WHO) Hand Hygiene Self-Assessment
      Framework (HHSAF) was conceived as a structured self-assessment tool to provide a
      situation analysis of hand hygiene resources, promotion and practices within
      healthcare facilities. AIM: To perform usability pretesting and reliability
      testing of the HHSAF. METHODS: The HHSAF draft was developed in consultation with
      experts to reflect key elements of the WHO Multimodal Hand Hygiene Improvement
      Strategy. Forty-two facilities were invited to pretest the draft HHSAF and
      complete a feedback survey. For reliability testing, two users in each facility
      completed the HHSAF independently. The reliability of each indicator, component
      subtotal and the overall score were estimated using the variance components
      model. After each phase, the tool was re-examined and modified as appropriate.
      FINDINGS: Twenty-seven indicators were selected during drafting. Twenty-six
      facilities in 19 countries completed pretesting (62% response rate), with total
      scores ranging from 35 to 480 (mean 262). The HHSAF took less than 2 h to
      complete for 21 facilities. Most agreed that the HHSAF was 'easy to use' (23/26)
      and 'useful for establishing facility status with regard to hand hygiene
      promotion' (24/26). Complete reliability responses were received from 41
      facilities in 16 countries. Reliability for the total score for the HHSAF and the
      subtotal of each of the five components ranged from 0.54 to 0.86. Seven
      indicators had poor reliability; these were examined for potential flaws and
      modified accordingly. CONCLUSION: This process confirmed the usability and
      reliability of this tool for the promotion of hand hygiene in health care.

PMID- 23149057
TI  - Carbapenemase-producing Enterobacteriaceae in Irish critical care units: results
      of a pilot prevalence survey, June 2011.
AB  - The epidemiology of carbapenemase-producing Enterobacteriaceae (CPE) in Ireland
      is changing, with an increase in the number of reported cases in late 2010 and
      early 2011. Reported cases were predominantly linked to critical care units. In
      June 2011, a four-week national pilot survey took place in 40 Irish critical care
      units (37 adult and three paediatric) to examine the prevalence of rectal
      carriage of CPE and inform national CPE screening guidelines. A total of 760
      screening swabs were taken over the study period, and CPE were not detected in
      any of the participating critical care units.

PMID- 23149058
TI  - Nosocomial myiasis in a patient with diabetes.
AB  - This report describes a case of nosocomial myiasis caused by larvae of Sarcophaga
      (Bercaea) africa. The parasitosis developed in an ulcer on the heel of a patient
      with type 2 diabetes. The ulcer was dressed when the deposition occurred. An
      experiment was performed in order to demonstrate the ability of Sarcophaga larvae
      to move through bandages and reach purulent wounds. This report highlights the
      need for particular attention, education and specific protocols in hospitals in
      order to avoid myiasis, which can compromise the organization's reputation for
      hygienic standards with possible legal consequences.

PMID- 23149059
TI  - Commentary.

PMID- 23149060
TI  - Preface. Special Issue featuring articles from the Eleventh International
      Symposium on Applied Bioinorganic Chemistry.

PMID- 23149061
TI  - Body mass normalisation for ultrasound measurements of lumbar multifidus and
      abdominal muscle size.
AB  - The purpose of this study was to determine if ratio scaling or allometric scaling
      is the more appropriate method for normalising ultrasound measurements of lumbar
      multifidus and abdominal muscle size to body mass. In a convenience sample of 62
      male career firefighters, cross-sectional area and thickness of the lumbar
      multifidus, as well as, thicknesses of the external oblique, internal oblique,
      and transverse abdominal muscles were assessed with ultrasonography. Ratio
      scaling entailed dividing muscle size by body mass, while allometric scaling
      entailed dividing muscle size by body mass raised to a power. Significant
      positive correlations (r = 0.25 to 0.49, p < 0.05) existed between body mass and
      all muscle size measurements, except for transverse abdominal thickness (r =
      0.21, p = 0.100). Ratio scaling was deemed inappropriate for normalising the
      muscle size measurements, because it merely reversed the direction of the
      correlations between body mass and the muscle size measurements (r = -0.31 to 
      0.50, p < 0.05), with external oblique abdominal thickness representing the only
      exception (r = -0.17, p = 0.192). Allometric scaling with derived allometric
      parameters was deemed appropriate for normalising muscle size measurements,
      because it caused the correlations between body mass and muscle size to become
      insignificant and near to zero (r = -0.06 to 0.00, p > 0.05). The current study
      provides allometric parameters that can be used to normalise muscle size
      measurements to body mass in male firefighters. Future research is needed to
      establish reference databases of population-specific allometric parameters in
      other groups.

PMID- 23149062
TI  - Extraction of left-ventricular torsion angle from the long-axis view by block
      matching algorithm: Comparison with the short-axis view.
AB  - INTRODUCTION: Due to limitations in measuring the torsion angle in the short-axis
      view when studying through-plane motion and so it is dependent on reference
      levels, in this study, we follow myocardial movement along the long-axis of the
      left ventricle (LV). Then, LV torsion is estimated in the long-axis view and
      compared with LV torsion in the short-axis view. MATERIALS AND METHODS: Two
      dimensional echocardiographic images of healthy persons were recorded in cine
      loop format position throughout four cardiac cycles at basal and apical levels in
      the long- and short-axis views. The motion vectors for reign of interest in the
      horizontal and vertical directions were obtained by block matching algorithm.
      Correlation between the values of automated analysis and manual tracing was
      performed by Pearson correlation analysis. Then, the maximum rotation angles of
      the short- and long-axis views at basal and apical levels were assessed. Left
      ventricular torsion angles in short-axis and long-axis views were calculated and
      compared based on rotation angles. RESULTS: There was a high correlation between
      the measured myocardial wall displacement of automated analysis (BM algorithm)
      and manual tracing (R=0.96, p<0.05). The maximum rotation angles of basal and
      apical levels in the short-axis view are 7.96+/-1.57 degrees  and 9.49+/-1.72
      degrees  and so in the long-axis view are 18.51+/-3.41 degrees  and 14.74+/-2.91
      degrees , respectively. The LV torsion angles and the time to reach peak LV
      torsion angles in the short-axis views are 17.26+/-2.53 degrees , 293+/-26ms and
      in the long-axis view are 32.26+/-5.60 degrees  and 290+/-22ms respectively.
      There was a high correlation between the left-ventricular torsion angle in the
      short-axis view and the long-axis view (R=0.92, p<0.05). There was also a high
      correlation between the time to reach peak left-ventricular torsion angle in the
      short-axis view as compared to the long-axis view (R=0.97, p<0.05). CONCLUSION:
      This study suggested that the LVtorsion angles in the short- and long-axis views
      were significantly correlated. It is concluded that torsion and rotation angles
      in the long-axis view are similar to those determined using the short-axis view.

PMID- 23149063
TI  - Porto-pulmonary hypertension exacerbated by platelet transfusion in a patient
      with ADAMTS13 deficiency.
AB  - We propose that porto-pulmonary hypertension (PPH) may arise as a consequence of
      deficiency of ADAMTS13 (a plasma metalloprotease that regulates von Willebrand
      factor size and reduces its platelet adhesive activity) and provide a clinical
      case history to support our hypothesis. A patient with non-cirrhotic intrahepatic
      portal hypertension (NCIPH), ulcerative colitis and celiac disease developed
      symptoms of PPH, which had advanced beyond levels which would have made her an
      eligible candidate for liver transplantation (mean pulmonary artery pressure
      (PAP) 49 mm Hg). She was known to have severe ADAMTS13 deficiency, which we
      considered to be causative of, or contributory to her NCIPH. We postulated that
      increasing porto-systemic shunting associated with advancing portal hypertension
      would make the next encountered vascular bed, the lung, susceptible to the
      pathogenic process that was previously confined to the portal system, with
      pulmonary hypertension as its consequence. Her pulmonary artery pressures fell
      significantly during the next year on weekly replacement of plasma ADAMTS13 by
      infusions of fresh frozen plasma and conventional drug treatment of her pulmonary
      hypertension. Her pulmonary artery pressures had fallen to acceptable levels
      when, in response to platelet infusion, it rose precipitously and dangerously.
      The sequence strongly supports our hypothesis that PPH is a consequence of
      ADAMTS13 deficiency and is caused by platelet deposition in afferent pulmonary
      vessels.

PMID- 23149064
TI  - Decrease in health-related quality of life associated with awareness of hepatitis
      C virus infection among people who inject drugs in Scotland.
AB  - BACKGROUND & AIMS: Chronic hepatitis C virus (HCV) infection can significantly
      reduce health-related quality of life (QoL), but it is not clear if reduction is
      associated with the infection or with being aware of one's infection status.
      Understanding the impact of a HCV diagnosis on QoL is essential to inform
      decision-making regarding screening/testing and treatment. METHODS: Using a cross
      sectional design, we assessed QoL in 2898 people who inject drugs (PWID),
      surveyed in Scotland during 2010 using EQ-5D. Multifactorial regression compared
      self-reported QoL between PWID who were (i) chronically HCV-infected and aware of
      their infected status, (ii) chronically HCV-infected but unaware, and (iii) not
      chronically infected. RESULTS: Median time since onset of injecting was 10years;
      not chronically infected PWID were younger and had shorter injecting careers than
      chronically infected PWID. Median EQ-5D was highest for the not chronically
      infected and the chronic/unaware groups (0.73) compared with the chronic/aware
      group (0.66). After adjustment for demographic and behavioural co-factors, QoL
      was significantly reduced in chronic/aware compared with chronic/unaware PWID
      (adjusted B=-0.09, p=0.005); there was no evidence for a difference in QoL
      between not chronically infected and chronic/unaware PWID (adjusted B=-0.03,
      p=0.13). CONCLUSIONS: Awareness of one's chronic HCV status was associated with
      reduced health-related QoL, but there was no evidence for further reduction
      attributable to chronic infection itself after adjusting for important covariate
      differences.

PMID- 23149065
TI  - Multi-target lentivirus specific to hepatocellular carcinoma: in vitro and in
      vivo studies.
AB  - BACKGROUND & AIMS: We aimed at investigating the effects of the targeted
      transduction of the Wtp53-pPRIME-miR30-shRNA gene into liver cancer cells, under
      the mediation of anti-alpha fetoprotein scFv-directed lentivirus, and the
      inhibitory effect of this system on liver cancer cells. METHODS: The result of
      infection was observed by fluorescence microscopy. Polymerase chain reaction and
      Western blotting were used to demonstrate the successful transduction and
      transcription of the Wtp53-pPRIME-miR30-shRNA-IGF1R gene. Cell growth was
      observed via the Cell-Counting Kit-8 Method, and cell apoptosis was detected by
      terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling. To observe
      further the effects of AFP-Wtp53-pPRIME-miR30-shRNA-IGF1R therapy in animals,
      models of BALB-C nude mice bearing subcutaneous human hepatocellular carcinoma
      were established. The influence of the growth of subcutaneously transplanted
      tumor, expression of Wtp53 protein, apoptosis, and microvessel formation on the
      overall level of AFP-Wtp53 pPRIME-miR30-shRNA-IGF1R were also evaluated. RESULTS:
      Recombinant lentivirus was successfully constructed, and its functional plaque
      forming unit titer was determined as 4.58 * 10(9)plaque-forming units/ml. A
      positive strand was detected by polymerase chain reaction and Western blotting.
      Lentiviral construction worked effectively in AFP-positive liver cancer cells. In
      vitro and in vivo experiments showed that the recombinant lentivirus was more
      efficacious in inhibiting the proliferation of Hep3B cells. CONCLUSIONS: The
      Wtp53-pPRIME-miR30-shRNA gene can be subjected to targeted transduction into
      liver cancer cells under the mediation of anti-alpha fetoprotein scFv-directed
      lentivirus. The Wtp53-pPRIME-miR30-shRNA system has targeting ability and lethal
      effects on liver cancer cells.

PMID- 23149067
TI  - [Clinical Images in Gastrology: high resolution esophageal pressure topography in
      the diagnosis of hiatal hernia].

PMID- 23149066
TI  - Contributors to self-reported health in a racially and ethnically diverse
      population: focus on Hispanics.
AB  - PURPOSE: To understand if Hispanics report health differently than other racial
      and ethnic groups after controlling for demographics and risk factors for poor
      health. METHODS: The sample (N = 5502) included 3201 women, 1767 black, 1859
      white, and 1876 Hispanic subjects from the Boston Area Community Health Survey, a
      population-based survey of English- and Spanish-speaking residents of Boston,
      Massachusetts, United States, aged 30-79 years in 2002-2005. Multiple logistic
      regression models were used to examine the association between race/ethnicity
      (including interview language for Hispanics) and fair/poor self-reported health
      (F/P SRH) adjusting for gender, age, socioeconomic status, depression, nativity,
      and comorbidities. RESULTS: Compared with whites, Hispanics interviewed in
      Spanish were seven times as likely to report F/P SRH (odds ratio, 7.7; 95%
      confidence interval, 4.9-12.2) after adjusting for potential confounders and
      those interviewed in English were twice as likely. In analyses stratified by
      depression and nativity, we observed stronger associations with Hispanic
      ethnicity in immigrants and nondepressed individuals interviewed in Spanish.
      CONCLUSIONS: Increased odds of F/P SRH persisted in the Hispanic group even when
      accounting for interview language and controlling for socioeconomic status, age,
      depression, and nativity, with interview language mitigating the association.
      These findings have methodological implications for epidemiologists using SRH
      across diverse populations.

PMID- 23149069
TI  - Family food insecurity and nutritional risk in adolescents from a low-income area
      of Rio de Janeiro, Brazil.
AB  - The study objective was to analyse the association between food insecurity and
      the weight and height status of adolescents from a low-income area in the
      metropolitan region of Rio de Janeiro, Brazil. The population-based cross
      sectional survey included 523 adolescents aged 12-18 years, selected by a three
      stage cluster sample. Dietary intake was ascertained with a food frequency
      questionnaire and family food insecurity was assessed with a validated
      questionnaire. The analysis estimated weighted means of energy and nutrient
      intakes by families' socioeconomic characteristics and the association between
      dietary intake with overweight and stunting. The prevalence of mild family food
      insecurity was 36%, and 24% of the families reported moderate or severe food
      insecurity. Overweight prevalence was 24%, and the prevalence of stunting was 9%,
      with no significant differences between sex or age groups. Family food insecurity
      was associated with unfavourable socioeconomic characteristics, but there was no
      association between socioeconomic characteristics (including family food
      insecurity) and overweight or stunting. Moderate or severe family food insecurity
      was inversely associated with intake of protein and calcium. In addition,
      stunting was associated with low calcium and iron intake. The co-existence of
      family food insecurity with overweight and stunting implies a high nutritional
      risk for adolescents from poor areas of Rio de Janeiro. Nevertheless, the
      observed absence of a statistical association between family food insecurity and
      weight status attests to the complexity of this issue.

PMID- 23149068
TI  - Age-dependent alterations in the presynaptic active zone in a Drosophila model of
      Alzheimer's disease.
AB  - The accumulation of beta amyloid (Abeta) can cause synaptic impairments, but the
      characteristics and mechanisms of the synaptic impairment induced by the
      accumulation of Abeta in Alzheimer's disease (AD) remain unclear. In identified
      single neurons in a newly developed Drosophila AD model, in which Abeta
      accumulates intraneuronally, we found an age-dependent reduction in the synaptic
      vesicle release probability that was associated with a decrease in the density of
      presynaptic calcium channel clusters and an increase in the presynaptic and
      postsynaptic contact length. Moreover, these alterations occurred in the absence
      of presynaptic bouton loss. In addition, we found that Abeta expression also
      produced an age-dependent decrease in the amount of Bruchpilot (Brp), which plays
      an important role in controlling Ca(2+) channel clustering and synaptic vesicle
      release in the presynaptic active zone. Our study indicates that the chronic
      accumulation of intraneuronal Abeta can induce functional and structural changes
      in the presynaptic active zone prior to a loss of presynaptic buttons in the same
      neuron.

PMID- 23149070
TI  - Dasatinib inhibits proliferation and induces apoptosis in the KASUMI-1 cell line
      bearing the t(8;21)(q22;q22) and the N822K c-kit mutation.
AB  - Activating mutations of the c-kit gene are frequently found in CBF (core binding
      factor) leukemias. We evaluated the effect of tyrosine kinase inhibitor dasatinib
      in leukemic cell lines bearing or not c-kit mutations. Our data demonstrate that
      in the AML Kasumi-1 cell line, bearing the N822K c-kit mutation, dasatinib is a
      potent suppressor of c-kit and Src kinase activity and inhibits the
      phosphorylation of their downstream target AKT, possibly through the Src-mediated
      VEGF/VEGFR receptor type 2 pathway. Dasatinib also effectively blocks
      proliferation and induces apoptosis through caspase-3 activation in Kasumi-1
      cells. These data further encourage the integration of dasatinib in the treatment
      of CBF AML with c-kit mutations in the context of clinical trials, which are
      eagerly anticipated.

PMID- 23149071
TI  - Recent progress in elucidating signalling proteolytic pathways in muscle wasting:
      potential clinical implications.
AB  - AIMS: Muscle wasting prevails with disuse (bedrest and immobilisation) and is
      associated with many diseases (cancer, sepsis, diabetes, kidney failure, trauma,
      etc.). This results first in prolonged hospitalisation with associated high
      health-care costs and second and ultimately in increased morbidity and mortality.
      The precise characterisation of the signalling pathways leading to muscle atrophy
      is therefore particularly relevant in clinical settings. DATA SYNTHESIS: Recent
      major papers have identified highly complex intricate pathways of signalling
      molecules, which induce the transcription of the muscle-specific ubiquitin
      protein ligases MAFbx/Atrogin-1 and MuRF1 that are overexpressed in nearly all
      muscle wasting diseases. These signalling pathways have been targeted with
      success in animal models of muscle wasting. In particular, these findings have
      revealed a finely tuned crosstalk between both anabolic and catabolic processes.
      CONCLUSIONS: Whether or not such strategies may be useful for blocking or at
      least limiting muscle wasting in weight losing and cachectic patients is becoming
      nowadays a very exciting clinical challenge.

PMID- 23149072
TI  - The role of gut microbiota in human obesity: recent findings and future
      perspectives.
AB  - AIMS: In recent years, gut microbiota have gained a growing interest as an
      environmental factor that may affect the predisposition toward adiposity. In this
      review, we describe and discuss the research that has focused on the involvement
      of gut microbiota in human obesity. We also summarize the current knowledge
      concerning the health effects of the composition of gut microbiota, acquired
      using the most recent methodological approaches, and the potential influence of
      gut microbiota on adiposity, as revealed by animal studies. DATA SYNTHESIS:
      Original research studies that were published in English or French until December
      2011 were selected through a computer-assisted literature search. The studies
      conducted to date show that there are differences in the gut microbiota between
      obese and normal-weight experimental animals. There is also evidence that a high
      fat diet may induce changes in gut microbiota in animal models regardless of the
      presence of obesity. In humans, obesity has been associated with reduced
      bacterial diversity and an altered representation of bacterial species, but the
      identified differences are not homogeneous among the studies. CONCLUSIONS: The
      question remains as to whether changes in the intestinal microbial community are
      one of the environmental causes of overweight and obesity or if they are a
      consequence of obesity, specifically of the unbalanced diet that often
      accompanies the development of excess weight gain. In the future, larger studies
      on the potential role of intestinal microbiota in human obesity should be
      conducted at the species level using standardized analytical techniques and
      taking all of the possible confounding variables into account.

PMID- 23149073
TI  - Renal denervation in cardiometabolic disease: concepts, achievements and
      perspectives.
AB  - AIMS: Growing evidence suggests that renal denervation may reduce elevated blood
      pressure values in resistant hypertension. More recently a number of studies have
      assessed the effects of the intervention on the dysmetabolic disarray (i.e.
      insulin resistance, glucose intolerance, and diabetes mellitus) frequently
      detectable in resistant hypertensive patients. The present viewpoint article
      critically examines the results obtained so far in this area. DATA SYNTHESIS: The
      results of the studies performed so far provide evidence that ablation of
      efferent and afferent sympathetic renal nerves improves glucose metabolism,
      reducing the incidence of glucose intolerance, fasting hyperglycemia and diabetic
      state in resistant hypertensive patients. The results, however, cannot be
      regarded as conclusive, taking into account that limitations in the experimental
      design of the studies published so far, as well as the frequent lack of specific
      subgroups data analysis, prevent to draw conclusive information on this issue.
      CONCLUSIONS: Although promising, the favorable results of renal denervation on
      the metabolic disarray frequently detectable in resistant hypertension require to
      be confirmed in large scale, randomized studies which are currently ongoing.

PMID- 23149074
TI  - Gazpacho consumption is associated with lower blood pressure and reduced
      hypertension in a high cardiovascular risk cohort. Cross-sectional study of the
      PREDIMED trial.
AB  - BACKGROUND AND AIM: Hypertension is a major public health problem and a leading
      cause of death and disability in both developed and developing countries,
      affecting one-quarter of the world's adult population. Our aim was to evaluate
      whether the consumption of gazpacho, a Mediterranean vegetable-based cold soup
      rich in phytochemicals, is associated with lower blood pressure (BP) and/or
      reduced prevalence of hypertension in individuals at high cardiovascular risk.
      METHODS AND RESULTS: We selected 3995 individuals (58% women, mean age 67 y) at
      high cardiovascular risk (81% hypertensive) recruited into the PREDIMED study.
      BP, weight, and dietary and physical activity data were collected. In
      multivariate linear regression analyses, after adjustment, moderate and high
      gazpacho consumption categories were associated with reduced mean systolic BP of 
      1.9 mm Hg [95% confidence interval (CI): -3.4; -0.6] and -2.6 mm Hg (CI: -4.2; 
      1.0), respectively, and reduced diastolic BP of -1.5 mm Hg (CI: -2.3; -0.6) and 
      1.9 mm Hg (CI: -2.8; -1.1). By multiple-adjusted logistic regression analysis,
      gazpacho consumption was associated with a lower prevalence of hypertension, with
      OR = 0.85 (CI: 0.73; 0.99) for each 250 g/week increase and OR = 0.73 (CI: 0.55;
      0.98) for high gazpacho consumption groups compared to the no-consumption group.
      CONCLUSIONS: Gazpacho consumption was inversely associated with systolic and
      diastolic BP and prevalence of hypertension in a cross-sectional Mediterranean
      population at high cardiovascular risk. The association between gazpacho intake
      and reduction of BP is probably due to synergy among several bioactive compounds
      present in the vegetable ingredients used to make the recipe.

PMID- 23149076
TI  - Ecdysone-dependent and ecdysone-independent programmed cell death in the
      developing optic lobe of Drosophila.
AB  - The adult optic lobe of Drosophila develops from the primordium during
      metamorphosis from mid-3rd larval stage to adult. Many cells die during
      development of the optic lobe with a peak of the number of dying cells at 24 h
      after puparium formation (h APF). Dying cells were observed in spatio-temporal
      specific clusters. Here, we analyzed the function of a component of the insect
      steroid hormone receptor, EcR, in this cell death. We examined expression
      patterns of two EcR isoforms, EcR-A and EcR-B1, in the optic lobe. Expression of
      each isoform altered during development in isoform-specific manner. EcR-B1 was
      not expressed in optic lobe neurons from 0 to 6h APF, but was expressed between 9
      and 48 h APF and then disappeared by 60 h APF. In each cortex, its expression was
      stronger in older glia-ensheathed neurons than in younger ones. EcR-B1 was also
      expressed in some types of glia. EcR-A was expressed in optic lobe neurons and
      many types of glia from 0 to 60 h APF in a different pattern from EcR-B1. Then,
      we genetically analyzed EcR function in the optic lobe cell death. At 0 h APF,
      the optic lobe cell death was independent of any EcR isoforms. In contrast, EcR
      B1 was required for most optic lobe cell death after 24 h APF. It was suggested
      that cell death cell-autonomously required EcR-B1 expressed after puparium
      formation. betaFTZ-F1 was also involved in cell death in many dying-cell
      clusters, but not in some of them at 24 h APF. Altogether, the optic lobe cell
      death occurred in ecdysone-independent manner at prepupal stage and ecdysone
      dependent manner after 24 h APF. The acquisition of ecdysone-dependence was not
      directly correlated with the initiation or increase of EcR-B1 expression.

PMID- 23149075
TI  - Preliminary evidence of genetic determinants of adiponectin response to
      fenofibrate in the Genetics of Lipid Lowering Drugs and Diet Network.
AB  - BACKGROUND AND AIMS: Adiponectin is an adipose-secreted protein that has been
      linked to changes in insulin sensitivity, high-density lipoprotein cholesterol
      levels, and inflammatory patterns. Although fenofibrate therapy can raise
      adiponectin levels, treatment response is heterogeneous and heritable, suggesting
      a role for genetic mediators. This is the first genome-wide association study of
      fenofibrate effects on circulating adiponectin. METHODS AND RESULTS: Plasma
      adiponectin was measured in participants of the Genetics of Lipid Lowering Drugs
      and Diet Network (n = 793) before and after a 3-week daily treatment with 160 mg
      of fenofibrate. Associations between variants on the Affymetrix Genome-Wide Human
      SNP Array 6.0 and adiponectin were assessed using mixed linear models, adjusted
      for age, sex, site, and family. We observed a statistically significant (P = 5 *
      10-8) association between rs2384207 in 12q24, a region previously linked to
      several metabolic traits, and the fenofibrate-induced change in circulating
      adiponectin. Additionally, our genome-wide analysis of baseline adiponectin
      levels replicated the previously reported association with CDH13 and suggested
      novel associations with markers near the PCK1, ZBP1, TMEM18, and SCUBE1 genes.
      The findings from the single marker tests were corroborated in gene-based
      analyses. Biological pathway analyses suggested a borderline significant
      association between the EGF receptor signaling pathway and baseline adiponectin
      levels. CONCLUSIONS: We present preliminary evidence linking several biologically
      relevant genetic variants to adiponectin levels at baseline and in response to
      fenofibrate therapy. Our findings provide support for fine-mapping of the 12q24
      region to investigate the shared biological mechanisms underlying levels of
      circulating adiponectin and susceptibility to metabolic disease.

PMID- 23149077
TI  - Neuroblast lineage-specific origin of the neurons of the Drosophila larval
      olfactory system.
AB  - The complete neuronal repertoire of the central brain of Drosophila originates
      from only approximately 100 pairs of neural stem cells, or neuroblasts. Each
      neuroblast produces a highly stereotyped lineage of neurons which innervate
      specific compartments of the brain. Neuroblasts undergo two rounds of mitotic
      activity: embryonic divisions produce lineages of primary neurons that build the
      larval nervous system; after a brief quiescence, the neuroblasts go through a
      second round of divisions in larval stage to produce secondary neurons which are
      integrated into the adult nervous system. Here we investigate the lineages that
      are associated with the larval antennal lobe, one of the most widely studied
      neuronal systems in fly. We find that the same five neuroblasts responsible for
      the adult antennal lobe also produce the antennal lobe of the larval brain.
      However, there are notable differences in the composition of larval (primary)
      lineages and their adult (secondary) counterparts. Significantly, in the adult,
      two lineages (lNB/BAlc and adNB/BAmv3) produce uniglomerular projection neurons
      connecting the antennal lobe with the mushroom body and lateral horn; another
      lineage, vNB/BAla1, generates multiglomerular neurons reaching the lateral horn
      directly. lNB/BAlc, as well as a fourth lineage, vlNB/BAla2, generate a diversity
      of local interneurons. We describe a fifth, previously unknown lineage, BAlp4,
      which connects the posterior part of the antennal lobe and the neighboring
      tritocerebrum (gustatory center) with a higher brain center located adjacent to
      the mushroom body. In the larva, only one of these lineages, adNB/BAmv3,
      generates all uniglomerular projection neurons. Also as in the adult, lNB/BAlc
      and vlNB/BAla2 produce local interneurons which, in terms of diversity in
      architecture and transmitter expression, resemble their adult counterparts. In
      addition, lineages lNB/BAlc and vNB/BAla1, as well as the newly described BAlp4,
      form numerous types of projection neurons which along the same major axon
      pathways (antennal tracts) used by the antennal projection neurons, but which
      form connections that include regions outside the "classical" olfactory circuit
      triad antennal lobe-mushroom body-lateral horn. Our work will benefit functional
      studies of the larval olfactory circuit, and shed light on the relationship
      between larval and adult neurons.

PMID- 23149078
TI  - Brachial artery waveforms for automatic blood pressure measurement.
AB  - Theoretically the auscultatory method using Korotkoff sounds is more related to
      the maximum artery closure status, while the oscillometric method is more related
      to the overall artery closure status under the cuff. Therefore, the latter is
      less accurate than the former. This work introduces a new method, which is more
      accurate than the oscillometric method and suitable for automatic devices. To
      monitor the maximum artery closure status, a piezoelectric film sensor is
      attached to the skin just above the brachial artery and under the central section
      of the cuff where maximum cuff pressure is transferred to the arm. Using the
      waveform features obtained by this sensor, measurement errors of 0.7+/-2.5 and
      1.27+/-4.53 mmHg were obtained for the systolic and diastolic pressure,
      respectively. These reflect small deviations from auscultatory clinical data.

PMID- 23149079
TI  - Center of mass trajectory and orientation to ankle and knee in sagittal plane is
      maintained with forward lean when backpack load changes during treadmill walking.
AB  - Maintaining the normal shape and amplitude of the vertical trajectory of the
      center of mass (COM) during stance has been shown to maximize the efficiency of
      unloaded gait. Kinematic adaptations to load carriage, such as forward lean have
      yet to be understood in relation to COM movement. The purpose of this study is to
      better understand how load impacts the vertical COM(TSYS) trajectory and to
      clarify the impact of forward lean as it relates to the dynamics of sagittal
      plane COM(TSYS) movement during stance with changing load. 17 subjects walked on
      treadmill at a constant preferred walking velocity while nine different loads
      ranging from 12.5% to 40% bodyweight were systematically added and removed from a
      backpack. Kinematic data were collected using an Optotrak, three-dimensional
      motion analysis system and used to estimate position of the COM as well as
      segment and COM-to-joint vector orientation angles. The shape and amplitude of
      the COM vertical trajectory was maintained across all loaded conditions. The
      orientations of COM-to-ankle and -knee vectors were maintained in all loaded
      conditions except the heaviest load (40% BW). Results suggest that forward lean
      changed linearly with changes in load to maintain the COM-to-ankle and -knee
      vector orientations. COM vertical trajectory was maintained by a combination of
      invariants including lower-limb segment angles and a constant direction of toe
      off impulse vector. The kinematic invariants found suggest a simplified control
      mechanism by which the system limits degrees of freedom and potentially minimizes
      torque about lower-extremity joints with added load.

PMID- 23149080
TI  - The influence of center-of-mass movements on the variation in the structure of
      human postural sway.
AB  - The present article investigates the influence of center-of-mass movements on the
      variation of the structure in human postural sway. Twelve healthy younger persons
      performed 60s quiet standing, 60s relaxed standing, and 10 min relaxed standing
      on two force plates. Center-of-pressure (CoP) and gravitational line (GL)
      profiles were calculated from the ground reaction forces and moments. The
      temporal variation of CoP structure was calculated by the local scaling exponent
      h(t) and a Monte Carlo surrogate test was used to identify phase couplings
      between temporal scales. The range of variation of h(t) was significantly larger
      in relaxed standing compared to quiet standing (p<0.00001) and highly correlated
      with the range of GL movements (r>0.76, p<0.001). However, the variation in h(t)
      was not generated by the GL movements because the CoP-GL traces was close to
      identical variation in h(t) (r>0.95, p<0.00001). The Monte Carlo surrogate test
      indicated the presence of intermittent phase couplings between the temporal
      scales of both CoP traces and the CoP-GL residuals in the periods with GL
      movements. The present results suggest that human posture is controlled by
      intermittent phase coupling of the CoP and GL movements. Furthermore, the
      investigation of the variation in CoP structure might extend existing theories of
      changes in postural control for example older persons and patients with a
      neurodegenerative disease.

PMID- 23149081
TI  - Does assessing patients' expectancies about chemotherapy side effects influence
      their occurrence?
AB  - CONTEXT: Increasing evidence suggests a link between patients' expectancies and
      post-chemotherapy side effects. However, it remains unclear whether asking
      patients about their expectancies might actually increase side effects.
      OBJECTIVES: The present study tested whether questioning first-time chemotherapy
      patients about their pretreatment expectancies for four common side effects
      influences the occurrence and/or severity of these side effects post-treatment
      and whether these pretreatment expectancies are predictive of post-treatment side
      effects. METHODS: Ninety-one first-time chemotherapy patients were randomly
      allocated to have their expectancies for nausea, fatigue, feelings of sadness,
      and loss of appetite assessed before their first infusion or to no such
      assessment. All patients then rated the occurrence and severity of these side
      effects at the end of their first chemotherapy cycle. RESULTS: There were no
      statistically significant differences in occurrence or severity of side effects
      in those who had their expectancies assessed compared with those who did not.
      There was, however, evidence of a statistically significant positive relationship
      between patients' pretreatment expectancies and their post-treatment reports of
      nausea, loss of appetite, and feelings of sadness, after controlling for age,
      sex, and baseline symptom levels. CONCLUSION: These findings suggest that patient
      expectancies might be a useful point of intervention for attempting to reduce the
      burden of chemotherapy-related side effects, as there do not appear to be any
      detrimental effects of asking patients to report their expectancies and their
      expectancies do appear related to the occurrence of post-treatment side effects.

PMID- 23149082
TI  - Traditional healers' views of the required processes for a "good death" among
      Xhosa patients pre- and post-death.
AB  - CONTEXT: South Africa faces enormous HIV-related mortality and increasing cancer
      incidence. Traditional healers are the preferred source of advice and care in
      Africa, and this is true for the large Xhosa ethnic group. OBJECTIVES: To provide
      more appropriate multidimensional, culturally suitable care at the end of life;
      this study aimed to identify the care needs and cultural practices of Xhosa
      patients and families at the end of life, from the perspective of traditional
      healers. METHODS: The study design was qualitative and cross-sectional. The
      research took place in a 300 km radius around East London, Eastern Cape, South
      Africa. Interviewees were Xhosa individuals who were recognized by their
      communities as traditional healers. Data from two focus groups and eight
      individual interviews were analyzed, using an inductive thematic approach.
      RESULTS: Data were elicited around the facilitation of a good death in terms of
      care needs before death and important rituals after death. Care needs before
      death focused on relief of psychosocial suffering; the importance of the spoken
      word at the deathbed; and the importance of a relationship and spiritual
      connection at the end of life. There were broad similarities across the rituals
      described after death, but these rituals were recognized to differ according to
      family customs or the dying person's wishes. CONCLUSION: Awareness of potential
      needs at the end of life can assist clinicians to understand the choices of their
      patients and develop effective end-of-life care plans that improve the outcomes
      for patients and families.

PMID- 23149084
TI  - Do corticosteroids provide analgesic effects in cancer patients? A systematic
      literature review.
AB  - CONTEXT: Corticosteroids are frequently used in cancer patients for their
      analgesic properties. The evidence for analgesic effects of corticosteroids in
      palliative care has not been established. OBJECTIVES: To assess the evidence for
      the use of corticosteroids in cancer pain management. METHODS: A systematic
      literature search was performed. The articles were evaluated according to the
      Grading of Recommendations Assessment, Development and Evaluations system by two
      independent reviewers. RESULTS: The search provided 514 references, four of which
      were included. Another two trials were identified from reference lists. Two of
      these six studies were excluded from the qualitative review. One crossover study
      showed a significant reduction in pain intensity of 13 (visual analogue 0-100
      scale) accompanied by significant lower analgesic consumption in favor of the
      steroid group. In another study, the addition of steroids did not have any effect
      on pain. In two studies, outcomes of pain intensity or analgesic consumption were
      not adequately reported. However, one of these studies showed significant pain
      reduction, whereas the other found no effect. Corticosteroids given in medium
      doses were well tolerated in studies for up to seven days. However, the studies
      indicated that corticosteroids may have serious toxicity and even higher
      mortality when administered in high doses over eight weeks. CONCLUSION:
      Corticosteroids may have a moderate analgesic effect in cancer patients. The
      paucity of relevant studies was striking; consequently, the evidence was graded
      as "very low." More studies addressing the analgesic efficacy in cancer patients
      are required.

PMID- 23149083
TI  - Genetic variations in interleukin-8 and interleukin-10 are associated with pain,
      depressed mood, and fatigue in lung cancer patients.
AB  - CONTEXT: A report by the National Cancer Institute identified that an important
      gap in symptom research is the investigation of multiple symptoms of cancer that
      might identify common biological mechanisms among cancer-related symptoms.
      OBJECTIVES: We applied novel statistical methods to assess whether variants of 37
      inflammation genes may serve as biologic markers of risk for severe pain,
      depressed mood, and fatigue in non-Hispanic white patients with non-small cell
      lung cancer. METHODS: Pain, fatigue, and depressed mood were assessed before
      cancer treatment. We used a generalized, multivariate, classification tree
      approach to explore the influence of single-nucleotide polymorphisms in the
      inflammation genes in pain, depressed mood, and fatigue in lung cancer patients.
      RESULTS: Among patients with advanced-stage disease, interleukin (IL)-8-T251A was
      the most relevant genetic factor for pain (odds ratio [OR] = 2.18, 95% CI = 1.34
      3.55, P = 0.001), depressed mood (OR = 0.37, 95% CI = 0.14-1.0), and fatigue (OR
      = 2.07, 95% CI = 1.16-3.70). Among those with early-stage non-small cell lung
      cancer, variants in the IL-10 receptor were relevant for fatigue among women.
      Specifically, women with Lys_Glu or Glu_Glu genotype in the IL-10 gene had a 0.49
      times lower risk of severe fatigue compared with those with Lys_Lys genotype (OR
      = 0.49, 95% CI = 0.25-0.92, P = 0.027). Among men with early-stage lung cancer, a
      marginal significance was observed for IL-1A C-889T, C/T, or T/T genotypes. These
      men had a lower risk of severe fatigue compared with those with C/C genotype (OR
      = 0.38, 95% CI = 0.13-1.06). CONCLUSION: The interaction of multiple inflammation
      genes, along with nongenetic factors, underlies the occurrence of symptoms. IL-8
      and IL-10 may serve as potential targets for treating multiple symptoms of
      cancer.

PMID- 23149085
TI  - Once-daily gastroretentive gabapentin for postherpetic neuralgia: integrated
      efficacy, time to onset of pain relief and safety analyses of data from two phase
      3, multicenter, randomized, double-blind, placebo-controlled studies.
AB  - CONTEXT: Treatment options for postherpetic neuralgia (PHN), a complication of
      herpes zoster, are commonly unsatisfactory and associated with adverse events.
      OBJECTIVES: To evaluate the efficacy, onset of pain relief, and safety of
      gastroretentive gabapentin (G-GR) in patients with PHN. METHODS: In two placebo
      controlled studies, 357 patients with PHN were randomized to 1800mg G-GR and 364
      patients were randomized to placebo taken with the evening meal. Patients
      underwent a two week titration, eight weeks of stable dosing, and one week of
      tapering. Efficacy assessments included change in average daily pain (ADP) score
      from baseline to Week 10, time to onset of pain relief, the proportion of
      patients feeling improved using the Patient Global Impression of Change, and the
      proportion of responders (>=30% pain reduction). RESULTS: At Week 10, patients
      randomized to G-GR reported greater reductions in ADP score compared with placebo
      (-37.0% vs. -29.1; P=0.0025). More G-GR patients felt improved compared with
      placebo (44% vs. 33%; P=0.003) and responded to treatment (54% vs. 41%; P=0.001).
      As early as Day 2, greater pain reductions were observed for the G-GR group
      compared with the placebo group (-6.6% vs. -1.6%; P=0.0017). The median time to a
      one point or greater reduction in ADP score was four days for G-GR and six days
      for placebo (P<0.0001). The most frequently reported adverse events were
      dizziness (G-GR, 11%; placebo, 2%) and somnolence (G-GR, 5%; placebo, 3%).
      CONCLUSION: PHN pain reduction after G-GR treatment can be observed as early as
      the second day of dosing and continues for at least 10 weeks.

PMID- 23149086
TI  - A national survey of infection control and antimicrobial stewardship structures
      in Irish long-term care facilities.
AB  - BACKGROUND: Information on infection prevention and control (IPC) and
      antimicrobial stewardship activities in Irish long-term care facilities (LTCFs)
      is limited. METHODS: A survey detailing IPC and antimicrobial stewardship
      activities, including staffing and bed capacity, was circulated to Irish LTCFs.
      RESULTS: Sixty-nine LTCFs (61 public, 8 private) were surveyed, 56 (81%) of which
      had an IPC practitioner. Thirty-five (51%) LTCFs had an IPC committee that met on
      average 5 times (range, 1-10) during the previous year. LTCFs with IPC
      practitioners based solely in the facility (n = 17) were more likely to have an
      IPC committee (P = .027). Antimicrobial guidelines were available in 28% (n = 19)
      and 16% (n = 11) had an antimicrobial stewardship committee in place. Medical
      care was provided by general practitioners in 51% (n = 35), by physicians
      employed by the LTCFs in 35% (n = 24), or by both in 14% (n = 10). Medical care
      and activities were coordinated in 45% (n = 31) of LTCFs. These LTCFs were more
      likely to have an IPC committee (P < .001), medical staff training (P < .001),
      and antimicrobial guidelines (P = .005) in place. CONCLUSION: There are
      significant gaps in Irish LTCFs' IPC and antibiotic stewardship programs and
      governance structures, highlighting the need for specific LTCF national
      initiatives.

PMID- 23149087
TI  - Prevention of methicillin-resistant Staphylococcus aureus infections in spinal
      cord injury units.
AB  - BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) health care
      associated infections (HAIs) are a concern in the 22 acute care Veterans Affairs
      (VA) spinal cord injury units where patients with unique rehabilitation and
      medical needs and a high risk of infection are treated. METHODS: A bundle was
      implemented in VA spinal cord injury units consisting of nasal surveillance for
      MRSA on admission/in-hospital transfer/discharge, contact precautions for
      patients colonized or infected with MRSA, an emphasis on hand hygiene, and an
      institutional culture change where infection control became everyone's
      responsibility. RESULTS: From October 2007, through June 2011, there were 51,627
      admissions/transfers/discharges and 816,254 patient-days of care in VA spinal
      cord injury units. The percentage of patients screened increased to >95.0%. The
      mean admission MRSA prevalence was 38.6% +/- 19.1%. Monthly HAI rates declined
      81% from 1.217 per 1,000 patient-days to 0.237 per 1,000 patient-days (P < .001).
      Bloodstream infections declined by 100% (P = .002), skin and soft-tissue
      infections by 60% (P = .007), and urinary tract infections by 33% (P = .07).
      CONCLUSION: Universal surveillance, contact precautions, hand hygiene, and an
      institutional culture change was associated with significant declines in MRSA
      HAIs in a setting with a high prevalence of MRSA colonization and a high risk for
      infection.

PMID- 23149088
TI  - Long-term outcome after extensive intestinal resection for chronic radiation
      enteritis.
AB  - INTRODUCTION: Management of chronic radiation enteritis is often controversial,
      particularly due to the risk of short bowel syndrome. METHODS: One hundred and
      seven chronic radiation enteritis patients with short bowel syndrome were studied
      retrospectively between 1980 and 2009. Survival and home parenteral nutrition
      dependence rates were evaluated with univariate and multivariate analysis.
      RESULTS: The survival probabilities were 93%, 67% and 44.5% at 1, 5 and 10 years,
      respectively. On multivariate analysis, survival was significantly decreased with
      residual neoplastic disease (HR=0.21 [0.11-0.38], p<0.001), an American Society
      of Anesthesiologists score >3 (HR=0.38 [0.20-0.73], p=0.004) and an age of
      chronic radiation enteritis diagnosis >60 years (HR=0.45 [0.22-0.89], p=0.02).
      The actuarial home parenteral nutrition dependence probabilities were 66%, 55%
      and 43% at 1, 2 and 3 years, respectively. On multivariate analysis, this
      dependence was significantly decreased when there was a residual small bowel
      length >100 cm (HR=0.35 [0.18-0.68], p=0.002), adaptive hyperphagia (HR=0.39
      [0.17-0.87], p=0.02) and the absence of a definitive stoma (HR=0.48 [0.27-0.84],
      p=0.01). CONCLUSION: The survival of patients with diffuse chronic radiation
      enteritis after extensive intestinal resection was good and was mainly influenced
      by underlying comorbidities. Almost two-thirds of patients were able to be weaned
      off home parenteral nutrition.

PMID- 23149089
TI  - Colonoscopy quality in Italy: a few suggestions for many problems.

PMID- 23149090
TI  - Systemic hypertension in an infant with unrepaired tetralogy of Fallot: case
      report.
AB  - Patients with severe right ventricular outflow tract obstruction in tetralogy of
      Fallot typically have right-to-left shunting, resulting in low pulmonary blood
      flow and cyanosis. Here we present the case of an infant with tetralogy of Fallot
      and severe pulmonary valve stenosis, complicated by systemic hypertension, the
      presence of which altered flow dynamics and possibly prevented cyanosis.

PMID- 23149091
TI  - Autographa californica M nucleopolyhedrovirus open reading frame 109 affects
      infectious budded virus production and nucleocapsid envelopment in the nucleus of
      cells.
AB  - Autographa californica M nucleopolyhedrovirus (AcMNPV) open reading frame 109
      (ac109) is conserved in all known baculovirus genomes, suggesting a crucial role
      in virus replication. Although viruses lacking ac109 have been previously
      characterized, the phenotypes differ from production of non-infectious virions to
      lack of virion production. To re-examine ac109 function, we constructed a
      recombinant AcMNPV bacmid, AcBAC109KO, with a deletion in ac109. We did not
      detect infectious budded virus after transfection of AcBAC109KO DNA into cells.
      In the nucleus, nucleocapsids had envelopment defects and polyhedra lacked
      virions. DNA synthesis and gene expression between AcBAC109KO and a control virus
      were similar. However, lower levels of non-infectious budded virus were detected
      from AcBAC109KO DNA-transfected cells compared to the parental virus using Q-PCR
      to detect viral DNA or by immunoblotting to detect a budded virus protein.
      Therefore, deletion of ac109 affects envelopment of nucleocapsids in the nucleus
      and the production of infectious budded virus.

PMID- 23149093
TI  - Novel live imaging techniques of cellular functions and in vivo tumors based on
      precise design of small molecule-based 'activatable' fluorescence probes.
AB  - Recently established rational design strategies for novel fluorescence probes,
      especially those based on photoinduced electron transfer and spirocyclization
      were reviewed. Based on these design strategies, various novel fluorescence
      probes were successfully developed including those for reactive oxygen species,
      reporter enzymes. Furthermore, in vivo cancer imaging techniques based on
      rationally designed activatable probes such as cancer-specific antibodies tagged
      with acidic-pH activatable fluorescence probes and peptidase activatable
      fluorescence probes were also discussed.

PMID- 23149092
TI  - Photocrosslinking approaches to interactome mapping.
AB  - Photocrosslinking approaches can be used to map interactome networks within the
      context of living cells. Photocrosslinking methods rely on use of metabolic
      engineering or genetic code expansion to incorporate photocrosslinking analogs of
      amino acids or sugars into cellular biomolecules. Immunological and mass
      spectrometry techniques are used to analyze crosslinked complexes, thereby
      defining specific interactomes. Because photocrosslinking can be conducted in
      native, cellular settings, it can be used to define context-dependent
      interactions. Photocrosslinking methods are also ideally suited for determining
      interactome dynamics, mapping interaction interfaces, and identifying transient
      interactions in which intrinsically disordered proteins and glycoproteins engage.
      Here we discuss the application of cell-based photocrosslinking to the study of
      specific problems in immune cell signaling, transcription, membrane protein
      dynamics, nucleocytoplasmic transport, and chaperone-assisted protein folding.

PMID- 23149094
TI  - Antitumor effect and toxicity of Lipusu in rat ovarian cancer xenografts.
AB  - Paclitaxel has yielded superior therapeutic effects in treating ovarian cancer
      after intraperitoneal (i.p.) injection. However, the dose-limiting toxicity of
      Cremophor-based paclitaxel was severe abdominal pain, likely caused by the
      excipients (Cremophor/ethanol). Lipusu, a paclitaxel liposome, has been widely
      applied for the treatment of ovarian cancer by intravenous administration in
      China. In order to find potential benefits of i.p. administration of Lipusu, we
      suppose that Lipusu could modulate paclitaxel toxicity without affecting
      antitumor activity compared with Cremophor-based paclitaxel (PTX). Antitumor
      effects, bone marrow toxicity, cardiotoxicity and biodistributions in NuTu19
      ovarian cancer-bearing rats, as well as the abdominalpain in normal mice were
      evaluated. Lipusu exerted similar antitumor effects similar to PTX, but much
      lower bone marrow toxicity and cardiotoxicity. Furthermore, Lipusu exhibited
      similar plasma drug exposure, higher exposure in tumor and pelvic lymph nodes and
      lower exposure in bone marrow and heart compared with PTX. Additionally, Lipusu
      induced notably lighter abdominalpain than PTX. These data suggested that Lipusu
      has similar antitumor effect and superior lymphatic targeting with reduced
      toxicities compared with PTX via i.p. route, which could be related with altered
      biodistributions. Therefore, Lipusu could be attractive for further evaluation of
      treating ovarian cancer by i.p. administration in clinic.

PMID- 23149095
TI  - Does smoking affect thyroid gland enlargement and nodule formation in iodine
      sufficient regions?
AB  - OBJECTIVES: The present study aimed to investigate the effect of smoking on
      thyroid nodule formation and goiter development in healthy subjects living in
      Istanbul, an iodine-sufficient region. This study was designed as a prospective,
      randomized, and observational study. METHODS: Included in the study were
      voluntary hospital staff and relatives of patients between the ages of 28 and 71
      who had no known disease or drug use, who have been living in Istanbul and had
      been smoking more than 10 cigarettes per day for at least 10years. Nonsmoker
      volunteers (45) shared similar demographic characteristics and were matched for
      age to the (46) smokers. By means of thyroid ultrasounds performed in all
      participants, volumes of the right and left lobes of the thyroid gland, and
      number, diameter and characteristics of nodules were evaluated. RESULTS:
      Comparing the smokers and nonsmokers, no statistically significant difference was
      determined in terms of presence of nodules and volumes of the left and right
      thyroid lobes (P=0.68, P=0.09, and P=0.63, respectively). Making enhanced diffuse
      enlargement of the thyroid gland, but not to a statistically significant degree.
      Smoking was observed to have no effect on non-toxic nodules, or the levels of
      thyroid-stimulating hormone, free thyroxin, free triiodothyronine, anti-thyroid
      peroxidase, or anti-thyroglobulin antibodies. CONCLUSIONS: Smoking does not
      effect, to a statistically significant degree goiter development thyroid nodule
      formation in iodine-sufficient regions like Istanbul.

PMID- 23149096
TI  - An evaluation of the first time performance of international medical graduates in
      the MRCOG Part 1 and Part 2 written examinations.
AB  - OBJECTIVES: To evaluate the performance of international medical graduates in the
      MRCOG Part 1 and Part 2 written examinations. STUDY DESIGN: Using the database of
      the Royal College of Obstetricians and Gynaecologists, a retrospective analysis
      was performed of the performance of overseas candidates who appeared for the
      first time in the Part 1 (n=11,863) and Part 2 written (n=5336) MRCOG
      examinations between 2000 and 2010. Candidates were grouped according to the RCOG
      geographical bands. RESULTS: In the Part 1 MRCOG examination the graduates of
      band E (India and Pakistan) and band B (Australia, New Zealand and Canada)
      performed well (pass rate 41.2% and 39.3% respectively) but the candidates of
      band C (East Africa 27.1%) and bands J and A (Europe 29.9%, Ireland 17.9%)
      underperformed. In the MRCOG Part 2 written examination the medical graduates of
      band D (Singapore and Hong Kong) and band B (Australia, New Zealand and Canada)
      performed well (pass rates 65.9% and 54.8%), but the candidates of band H (Middle
      East, pass rate 8.5%) and band C (Africa West, pass rate 12.7%) performed worse
      than the remaining cohort. The greatest number of candidates in the Part 2
      written examinations appeared from India and Pakistan (n=2999, pass rate 22.2%).
      CONCLUSION: Our results have shown that there is variation in performance among
      the IMG from different geographical regions in the Part 1 and Part 2 written
      MRCOG examinations.

PMID- 23149097
TI  - Timing of clade divergence and discordant estimates of genetic and morphological
      diversity in the Slender Madtom, Noturus exilis (Ictaluridae).
AB  - Phylogeographic relationships, the timing of clade diversification, and the
      potential for cryptic diversity in the Slender Madtom, Noturus exilis, was
      investigated using mitochondrial Cyt b, nuclear RAG2, shape analysis, and
      meristic and pigmentation data. Three well-supported and deeply divergent clades
      were recovered from analyses of genetic data: Little Red River (White River
      drainage) clade, Arkansas+Red River (Mississippi River) clade, and a large clade
      of populations from the rest of the range of the species. Recovered clades showed
      little to no diagnostic morphological differences, supporting previous hypotheses
      of morphological conservatism in catfishes, and indicating morphology may
      commonly underestimate diversity in this group of fishes. The Little Red River
      clade is the most distinct lineage of N. exilis with 11 POM pores (vs. 10 in
      other populations) and unique Cyt b haplotypes and RAG 2 alleles. However,
      treating it as a species separate from N. exilis would imply that the other major
      clades of N. exilis are more closely related to one another than they are to the
      Little Red River clade, which was not supported. The UCLN age estimate for
      Noturus was 23.9mya (95% HPD: 13.49, 35.43), indicating a late Oligocene to early
      Miocene origin. The age of N. exilis was estimated as late Miocene at 9.7mya (95%
      HPD: 5.32, 14.93). Diversification within the species spanned the late Miocene to
      mid-Pleistocene. The largest clade of N. exilis, which dates to the late Miocene,
      includes populations from the unglaciated Eastern and Interior Highlands as well
      as the previously glaciated Central Lowlands. Diversification of this clade
      coincides with a drastic drop in sea-level and diversification of other groups of
      Central Highlands fishes (Centrarchidae and Cyprinidae). Sub-clades dating to the
      Pleistocene show that northern populations occurring in previously glaciated
      regions resulted from dispersal from populations in the Ozarks up the Mississippi
      River following retreat of the Pleistocene glaciers. Pre-Pleistocene vicariance,
      such as drainage pattern changes of the Mississippi River, also played a
      prominent role in the history of the species. The incorporation of a temporal
      estimate of clade diversification revealed that in some instances,
      phylogeographic breaks shared with other aquatic species were best explained by
      different or persistent vicariant events through time, rather than a single
      shared event.

PMID- 23149098
TI  - The composition of animal ethics committees needs to change.

PMID- 23149099
TI  - The application of plastic compression to modulate fibrin hydrogel mechanical
      properties.
AB  - The inherent biocompatibility of fibrin hydrogels makes them an attractive
      material for use in a wide range of tissue engineering applications. Despite
      this, their relatively low stiffness and high compliance limits their potential
      for certain orthopaedic applications. Enhanced mechanical properties are
      desirable so as to withstand surgical handling and in vivo loading after
      implantation and additionally, can provide important cues to cells seeded within
      the hydrogel. Standard methods used to enhance the mechanical properties of
      biological scaffolds such as chemical or thermal crosslinking cannot be used with
      fibrin hydrogels as cell seeding and gel formation occurs simultaneously. The
      objective of this study was to investigate the use of plastic compression as a
      means to improve the mechanical properties of chondrocyte-seeded fibrin hydrogels
      and to determine the influence of such compression on cell viability within these
      constructs. It was found that the application of 80% strain to fibrin hydrogels
      for 30 min (which resulted in a permanent strain of 47.4%) produced a 2.1-fold
      increase in the subsequent compressive modulus. Additionally, chondrocyte
      viability was maintained in the plastically compressed gels with significant
      cellular proliferation and extracellular matrix accumulation observed over 28
      days of culture. In conclusion, plastic compression can be used to modulate the
      density and mechanical properties of cell-seeded fibrin hydrogels and represents
      a useful tool for both in theatre and in vitro tissue engineering applications.

PMID- 23149100
TI  - Transillumination defects following in-the-bag single-piece intraocular lens
      implantation and trabeculectomy with mini-shunt.
AB  - An 80-year-old woman of mixed ethnicity developed significant iris
      transillumination defects following phacoemulsification with in-the-bag
      implantation of a single-piece hydrophobic acrylic intraocular lens (IOL) and
      trabeculectomy with insertion of an Express mini-shunt. With the exception of
      modest anterior chamber shallowing in the first few weeks postoperatively, the
      surgery and postoperative course were uneventful. The observed iris defects are
      thought to have been caused by contact between the IOL-capsule complex and the
      posterior iris during shallowing of the anterior chamber. No other cases in the
      peer-reviewed literature have identified iris defects secondary to implantation
      of a single-piece monofocal hydrophobic acrylic IOL when the optic and haptics
      remained entirely within the capsular bag.

PMID- 23149101
TI  - Saccular sensitivity to sound.

PMID- 23149102
TI  - Connecting the nucleus to the cytoskeleton by SUN-KASH bridges across the nuclear
      envelope.
AB  - The nuclear-cytoskeleton connection influences many aspects of cellular
      architecture, including nuclear positioning, the stiffness of the global
      cytoskeleton, and mechanotransduction. Central to all of these processes is the
      assembly and function of conserved SUN-KASH bridges, or LINC complexes, that span
      the nuclear envelope. Recent studies provide details of the higher order assembly
      and targeting of SUN proteins to the inner nuclear membrane. Structural studies
      characterize SUN-KASH interactions that form the central link of the nuclear
      envelope bridge. KASH proteins at the outer nuclear membrane link the nuclear
      envelope to the cytoskeleton where forces are generated to move nuclei.
      Significantly, SUN proteins were recently shown to contribute to the progression
      of laminopathies.

PMID- 23149104
TI  - Synthesis, characterization and hydration analysis of a novel
      epoxy/superplasticizer oilwell cement slurry--some mechanistic features by
      solution microcalorimetry.
AB  - A new epoxy/polyacrylate-modified oilwell cement slurry was synthesized. The
      features of the new slurry were evaluated in relation to a standard cement slurry
      (w/c=0.5). The characterization of the slurries was performed by Raman, XRD,
      TG/DTG and solid-state diffuse reflectance spectroscopy. The main morphological
      features of the new slurry were preserved, even after long-term contact with HCl
      in aqueous solution. The hydration of the slurries was studied by heat-conduction
      microcalorimetry. The exothermic microcalorimetric outputs were well fitted to a
      three-parameter kinetic model. The analysis of both thermodynamic and kinetic
      results from microcalorimetry have pointed out that diffusional growth from non
      stoichiometric mixtures is the main mechanistic feature of the hydration of the
      cement slurries. The results of this study underline the excellent features of
      the new epoxy/superplasticizer-modified cement slurry for using in severe acidic
      environments of oilwells.

PMID- 23149105
TI  - Direct and rapid quantum dots labelling of Escherichia coli cells.
AB  - Here, we supplied a direct and rapid quantum dots labelling method of bacterial
      cells in food, water and environmental contaminations. Outer layers of
      Escherichia coli cells prevent cells from direct interactions with molecules and
      objects such as quantum dots. Permeabilization treatment of E. coli cells may
      facilitate macromolecules penetrate cell walls and improve internal bacterial
      quantum dots (QDs) labelling. In this work, we investigated direct internal QDs
      labelling of E. coli cells permeabilized using three methods including chloroform
      SDS treatment, lysozyme-EDTA treatment and osmotic shock treatment. Effects of
      permeabilization were analysed by scanning electronic microscopy and measuring
      activity of alkaline phosphatase (PhoA) released from periplasm. Internal
      bacterial QDs labelling was monitored by flow cytometry and fluorescent
      microscopy. After chloroform-SDS or lysozyme-EDTA treatment, cells could be
      directly labelled with QDs. No interaction was observed between osmotic shock
      treated cells and QDs. The mechanism of cell permeabilization explaining
      different labelling efficiency has been established. The QDs labelling approach
      presented in this work provides a simple, rapid and sensitive detection method
      for multiple purpose bacterial analysis in combination with biological
      techniques.

PMID- 23149103
TI  - Effector CD8 T cell trafficking within the liver.
AB  - CD8 T cells play a critical role in several pathological conditions affecting the
      liver, most notably viral hepatitis. Accordingly, understanding the mechanisms
      that modulate the intrahepatic recruitment of CD8 T cells is of paramount
      importance. Some of the rules governing the behavior of these cells in the liver
      have been characterized at the population level, or have been inferred by
      studying the intrahepatic behavior of other leukocyte subpopulations. In contrast
      to most microvascular beds where leukocyte adhesion is restricted to the
      endothelium of post-capillary venules, it is now becoming clear that in the liver
      leukocytes, including CD8 T cells, can efficiently interact with the endothelium
      of hepatic capillaries (i.e. the sinusoids). While physical trapping has been
      proposed to play an important role in leukocyte adhesion to hepatic sinusoids,
      there is mounting evidence that T cell recruitment to the liver is highly
      regulated and depends on recruitment signals that are either constitutive or
      induced by inflammation. We review here several specific adhesive mechanisms that
      have been shown to regulate CD8 T cell trafficking within the liver, as well as
      highlight recent data that establish platelets as key cellular regulators of
      intrahepatic CD8 T cell accumulation.

PMID- 23149106
TI  - Eu(III) uptake on rectorite in the presence of humic acid: a macroscopic and
      spectroscopic study.
AB  - This work contributed to the comprehension of humic acid (HA) effect on Eu(III)
      uptake to Na-rectorite by batch sorption experiments, model fitting, scanning
      electron microscopy, powder X-ray diffraction, Fourier transform infrared
      spectroscopy, X-ray photoelectron spectroscopy, and extended X-ray absorption
      fine structure (EXAFS) spectroscopy. At low pH, the presence of HA enhanced
      Eu(III) sorption on Na-rectorite, while reduced Eu(III) sorption at high pH. The
      experimental data of Eu(III) sorption in the absence and presence of HA were
      simulated by the diffuse-layer model well with the aid of FITEQL 3.2 software.
      The basal spacing of rectorite became large after Eu(III) and HA sorption on Na
      rectorite. Some of Eu(III) ions and HA might be intercalated into the interlayer
      space of Na-rectorite. EXAFS analysis showed that the R(Eu-O) (the bond distance
      of Eu and O in the first shell of Eu) and N values (coordination number) of
      Eu(III)-HA-rectorite system were smaller than those of Eu(III)-rectorite system.

PMID- 23149107
TI  - A survey of place-exchange reaction for the preparation of water-soluble gold
      nanoparticles.
AB  - Water-soluble gold nanoparticles (AuNPs) have gained considerable attention
      because they offer a myriad of potential applications, especially in the fields
      of biology and medicine. One method to prepare such gold nanoparticles is through
      the well-known Murray place-exchange reaction. In this method, precursor gold
      nanoparticles, bearing labile ligands and with very good size distribution, are
      synthesized first, and then reacted with a large excess of the desired ligand. We
      report a comparison of the reactivity of several known precursor gold
      nanoparticles (citrate-stabilized, pentanethiol-stabilized, tetraoctylammonium
      bromide-stabilized, and 4-dimethylaminopyridine-stabilized) to several
      biologically relevant ligands, including amino acids, peptides, and
      carbohydrates. We found that citrate-stabilized and 4-dimethylaminopyridine
      stabilized gold nanoparticles have broader reactivities than the other precursors
      studied. Citrate-stabilized gold nanoparticles are more versatile precursors
      because they can be prepared in a wide range of sizes and are very stable. The
      hydrophobic pentane-stabilized gold nanoparticles made them "inert" toward highly
      water-soluble ligands. Tetraoctylammonium bromide-stabilized gold nanoparticles
      exhibited selective reactivity, especially for small, unhindered and amphiphilic
      ligands. Depending on the desired ligand and size of AuNPs, a judicious selection
      of the available precursors can be made for use in place-exchange reactions. In
      preparing water-soluble AuNPs with biologically relevant ligands, the nature of
      the incoming ligand and the size of the AuNP should be taken into account in
      order to choose the most suitable place-exchange procedure.

PMID- 23149108
TI  - Post-synthesis surface-modified silicas as adsorbents for heavy metal ion
      contaminants Cd(II), Cu(II), Cr(III), and Sr(II) in aqueous solutions.
AB  - To analyze the influence of silica surface modification and confined space
      effects on specific interactions of divalent and trivalent metal cations with
      surface functionalities, three different high surface area silicas with different
      pore size distributions were modified with the following organosilanes: 3
      aminopropyltriethoxysilane, N-(2-aminoethyl)-3-aminopropyltriethoxysilane, 3
      (trimethoxysilylpropyl)diethylenetriamine, N
      (triethoxysilylpropyl)ethylenediaminetriacetic acid (EDTrA), and 3-(2,4
      dinitrophenylamino)propyltriethoxysilane. The silicas were characterized by N(2)
      adsorption and reflectance FTIR spectroscopy before and after surface
      modification. N(2) adsorption and pore size distributions showed an increase in
      the pore width for all EDTrA-modified silicas, opposite to what occurred with the
      other organosilanes. Adsorption isotherms of Cd(II), Cr(III), Cu(II), and Sr(II)
      obtained from aqueous solutions were compared and analyzed by silica type,
      organosilane functional group, and metal adsorbed. Reflectance FTIR spectroscopy
      was used to probe the acetate functionality in EDTrA as a function of adsorbed
      metal content. A band shift to higher energy for Cr(III) on the wide pore silica
      studied indicated that the interaction with the acetate groups can be probed in
      this manner. In general, the wider pore distribution silica provided larger
      adsorption maxima, whereas the narrower pore distribution silica provided more
      favorable DeltaG because of stronger binding of the cations. Cr(III) and Cu(II)
      exhibited larger adsorption maxima compared to Cd(II) and Sr(II), with the
      grafted organosilanes studied since the first cations have a greater
      charge/radius ratio than the second ones that provide a greater binding energy.

PMID- 23149109
TI  - From molecules to behavior and the clinic: Integration in chronobiology.
AB  - Chronobiology, especially the study of circadian rhythms, provides a model
      scientific field in which philosophers can study how investigators from a variety
      of disciplines working at different levels of organization are each contributing
      to a multi-level account of the responsible mechanism. I focus on how the
      framework of mechanistic explanation integrates research designed to decompose
      the mechanism with efforts directed at recomposition that relies especially on
      computation models. I also examine how recently the integration has extended
      beyond basic research to the processes through which the disruption of circadian
      rhythms contributes to disease, including various forms of cancer. Understanding
      these linkages has been facilitated by discoveries about how circadian mechanisms
      interact with mechanisms involved in other physiological processes, including the
      cell cycle and the immune system. 

PMID- 23149110
TI  - Integration of specialties: An institutional and organizational view.
AB  - By what mechanisms of organizational and institutional change do different
      specialties succeed in accommodating and working with one another? How do these
      mechanisms function over time to support and retard the emergence and stability
      of new knowledge? This paper considers two such mechanisms, metawork (work that
      determines the organization of work) and common knowledge (knowledge that
      participants know is known by all participants). These mechanisms integrate
      specialties by making the activities of multiple specialties dependent upon one
      another, and by segmenting the common effort from the parent specialties.
      Integration of specialties can lead to the development of new specialties.
      Integration is facilitated and impeded by the anchoring of specialties in the
      system of institutions that participate in research. Host organizations, degree
      programs, sponsors, associations, regulators, and other organizations provide
      resources and impose demands that shape research. Some of these impacts are
      obvious and direct; others are indirect and more subtle. The research specialties
      form a network (not a hierarchy) in which connections constantly form and reform,
      and in which the influence of different anchoring institutions are constantly
      waxing and waning. The complexity of connections and their pattern of change are
      especially obvious in the life sciences, which are an especially good place to
      study problems of integration. 

PMID- 23149111
TI  - Clinical skill and knowledge requirements of health care providers caring for
      children in disaster, humanitarian and civic assistance operations: an
      integrative review of the literature.
AB  - INTRODUCTION: Military health care providers (HCPs) have an integral role during
      disaster, humanitarian, and civic assistance (DHCA) missions. Since 50% of
      patients seen in these settings are children, military providers must be prepared
      to deliver this care. PURPOSE: The purpose of this systematic, integrative review
      of the literature was to describe the knowledge and clinical skills military
      health care providers need in order to provide care for pediatric outpatients
      during DHCA operations. DATA SOURCES: A systematic search protocol was developed
      in conjunction with a research librarian. Searches of PubMed and CINAHL were
      conducted using terms such as Disaster*, Geological Processes, and Military
      Personnel. Thirty-one articles were included from database and manual searches.
      CONCLUSIONS: Infectious diseases, vaccines, malnutrition, sanitation and wound
      care were among the most frequently mentioned of the 49 themes emerging from the
      literature. Concepts included endemic, environmental, vector-borne and vaccine
      preventable diseases; enhanced pediatric primary care; and skills and knowledge
      specific to disaster, humanitarian and civic assistance operations. IMPLICATIONS
      FOR PRACTICE: The information provided is a critical step in developing
      curriculum specific to caring for children in DHCA. While the focus was military
      HCPs, the knowledge is easily translated to civilian HCPs who provide care to
      children in these situations.

PMID- 23149113
TI  - [Kawasaki disease without fever?].

PMID- 23149112
TI  - Gender differences in socio-demographic and clinical characteristics of
      methamphetamine inpatients in a Chinese population.
AB  - BACKGROUND: Over the past two decades, China has experienced a dramatic increase
      in methamphetamine (MA) abuse. This study examined gender-specific socio
      demographic and clinical characteristics of MA use among Han Chinese, which has
      previously received little systematic study. METHODS: This analysis described MA
      related socio-demographic and clinical characteristics in a broad cross-sectional
      sample (n=1464; male/female=1185/279), and examined differences between males and
      females in MA use history, MA initiation, MA-related subjective feelings and
      behaviors, and withdrawal symptoms. RESULTS: Most MA abusers (about 72%) were
      young (in their 20s or 30s), with women being 5 years younger than men on
      average. More males (33.2%) were married than females (21.9%). The average body
      mass index (BMI) was significantly lower in this MA abuser sample compared to the
      age-matched healthy controls. Moreover, the BMI of females was significantly
      lower than that of males. The laboratory tests showed that the blood levels of
      glucose, cholesterol and triglyceride were all significantly higher in males than
      females. Females used MA at a younger age compared to males. The most frequent
      route of MA use was smoking (90.9%). Males were more likely to use another drug,
      and more likely to be hospitalized. However, many characteristics and behaviors
      of MA use are similar for males and females, including the route, the dose and
      duration of MA use, and relapse status. CONCLUSION: Although there were some male
      female similarities in MA use parameters, significant differences do exist that
      may have implications for gender-specific research as well as for prevention and
      treatment strategies.

PMID- 23149114
TI  - [Eikenella corrodens infection after a human bite].

PMID- 23149115
TI  - The transmembrane protein Opy2 mediates activation of the Cek1 MAP kinase in
      Candida albicans.
AB  - MAPK pathways are conserved and complex mechanisms of signaling in eukaryotic
      cells. These pathways mediate adaptation to different stress conditions by a core
      kinase cascade that perceives changes in the environment by different upstream
      elements and mediates adaptation through transcription factors. In the present
      work, the transmembrane protein Opy2 has been identified and functionally
      characterized in Candida albicans. This protein is required to trigger Cek1
      phosphorylation by different stimuli such as the resumption of growth from
      stationary phase or the addition of the cell wall disturbing compounds zymolyase
      and tunicamycin. opy2 mutants display susceptibility to cell wall disturbing
      compounds like Congo red. However, it does not play a role in the adaptation to
      high osmolarity or oxidative stress, in close contrast with the situation for the
      homologous protein in Saccharomyces cerevisiae. The over-expression of Opy2 in a
      S. cerevisiae opy2ssk1 mutant partially complemented the osmosensitivity on solid
      medium by a Hog1-independent mechanism as well as the abnormal morphology
      observed in this mutant under high osmolarity. The electrophoretic pattern of
      CaOpy2 tagged version in S. cerevisiae suggested similar post-translational
      modification in both microorganisms. This protein is also involved in
      pathogenesis as revealed by the fact that opy2 mutants displayed a significantly
      reduced virulence in the Galleria mellonella model.

PMID- 23149117
TI  - The shock of the 'Nuer': the UK experience with new non-Luer neuraxial equipment
      and implications for obstetric anaesthesia.

PMID- 23149116
TI  - The effect of prescribed fluid consumption on physiology and work behavior of
      wildfire fighters.
AB  - The purpose of this study was to examine 1) wildfire fighters' ability to consume
      the prescribed fluid volume (1200 mL h(-1)), 2) the effect of fluid intake on
      plasma sodium and hydration, and 3) the effect of fluid intake on firefighters'
      heart rate, core temperature and activity during emergency suppression shifts.
      METHODS: Thirty-four firefighters were divided into ad libitum (AD, n = 17) and
      prescribed (PR, n = 17) drinking groups. RESULTS: PR drinkers did not meet the
      prescribed fluid target, yet consumed over double the volume of AD drinkers. No
      differences between groups in plasma sodium or hydration were noted. PR drinking
      resulted in lower core temperature between 2 and 6 h. This did not coincide with
      reduced cardiovascular strain, greater work activity or larger distances covered
      when compared to AD drinkers. CONCLUSION: Extra fluid consumption (above AD) did
      not improve firefighter activity or physiological function (though PR
      firefighters core temperature was lower earlier in their shift). Firefighter can
      self-regulate their fluid consumption behavior and work rate to leave the
      fireground euhydrated.

PMID- 23149118
TI  - Response to variable light intensity in photoacclimated algae and cyanobacteria
      exposed to atrazine.
AB  - Atrazine is frequently detected in freshwater ecosystems exposed to agricultural
      waste waters and runoffs worldwide and it can affect non-target organisms (mainly
      photoautotrophic) and modify community structure. Meanwhile, light environment is
      known to vary between aquatic ecosystems, but also before and during the exposure
      to atrazine and these variations may modify the sensitivity to atrazine of
      photoautotroph organisms. In this study, 10 species of phytoplankton
      (chlorophytes, baccilariophytes and cyanophytes) acclimated to low or high light
      intensities were exposed to atrazine and light of different intensities to
      compare their combined effect. Our data showed that chlorophytes and
      baccilariophytes were more resistant to atrazine compared to cyanophytes for all
      light conditions. Atrazine was found to inhibit Phi'(M), Psi(0), P(M) and non
      photochemical quenching for all species indicating an effect on electron
      transport, primary production and photoregulation processes. These data also
      indicate a higher sensitivity of Psi(0) (average Psi(0)-EC(50) of 91 +/- 11 nM or
      19.6 +/- 0.9 MUgL(-1)) compared to Phi'(M) (average Phi'(M)-EC(50) of 217 +/- 19
      nM or 46.8 +/- 4.1 MUgL(-1)) and suggest that photoregulation processes activated
      in presence of light decrease the effect of atrazine. We also showed that
      increasing light intensity decreased Phi'(M)-EC(50) in both low (except
      baccilariophytes) and high light acclimated conditions. Despite this similarity,
      most species acclimated to high light were found to have higher or similar
      Phi'(M)-EC(50) compared to low light acclimated cells and thus, were less
      sensitive to atrazine in low light and high light environments. We concluded that
      an increase in the plastoquinone pool induced by acclimation to high light
      decreased the sensitivity to atrazine in phytoplankton and we hypothesized that
      the effect observed was the result of a dilution of atrazine toxicity through
      increased binding site availability (quinones) combined with increased
      photoregulation processes capacity.

PMID- 23149119
TI  - [Validation inspection of prescription drugs in Spain: current situation from a
      health professional perspective after its introduction in electronic form].
AB  - AIMS: To assess the current situation of the inspection validation of
      prescriptions (IVP) in Spain since the introduction of the electronic procedure
      (EP) from the healthcare professionals' perspective. DESIGN: Observational, cross
      sectional study, in two phases; combining qualitative and quantitative
      techniques. SETTING: Primary Care (PC), Secondary Care (SC) and the health care
      management sector. PARTICIPANTS: Primary care physicians (PCPs),
      endocrinologists, medical inspectors, pharmacists and health Authorities of
      Autonomous Communities (AACC). METHOD: Semi-structured surveys and Computer
      Assisted Telephone Interviewing. RESULTS: The IVP presents three modalities in
      Spain: manual, electronics and electronics linked to electronic prescription. The
      participants of the same level of management perceive in a similar way the
      purpose of the IVP, and there exist differences between the different levels of
      interviewed managers. Differences exist in the situation of EP between AACC. It
      is more implemented in primary care (PC) than in specialized (63% vs 37%), with
      similar degree in urban and rural areas. Six of 17 AACC presented a public access
      to the corresponding legislation. CONCLUSION: The IVP is perceived as a tool for
      the economic control in expenditure on drugs and as additional administrative
      load in PC. The rhythm of implementation of EP differs between AACC as well as
      the access to the regulation.

PMID- 23149120
TI  - Assessing your mood online: acceptability and use of Moodscope.
AB  - BACKGROUND: Moodscope is an entirely service-user-developed online mood-tracking
      and feedback tool with built-in social support, designed to stabilize and improve
      mood. Many free internet tools are available with no assessment of acceptability,
      validity or usefulness. This study provides an exemplar for future assessments.
      Method A mixed-methods approach was used. Participants with mild to moderate low
      mood used the tool for 3 months. Correlations between weekly assessments using
      the Patient Health Questionnaire (PHQ-9) and the Generalized Anxiety Disorder
      Assessment (GAD-7) with daily Moodscope scores were examined to provide validity
      data. After 3 months, focus groups and questionnaires assessed use and usability
      of the tool. RESULTS: Moodscope scores were correlated significantly with scores
      on the PHQ-9 and the GAD-7 for all weeks, suggesting a valid measure of mood. Low
      rates of use, particularly toward the end of the trial, demonstrate potential
      problems relating to ongoing motivation. Questionnaire data indicated that the
      tool was easy to learn and use, but there were concerns about the mood
      adjectives, site layout and the buddy system. Participants in the focus groups
      found the tool acceptable overall, but felt clarification of the role and target
      group was required. CONCLUSIONS: With appropriate adjustments, Moodscope could be
      a useful tool for clinicians as a way of initially identifying patterns and
      influences on mood in individuals experiencing low mood. For those who benefit
      from ongoing mood tracking and the social support provided by the buddy system,
      Moodscope could be an ongoing adjunct to therapy.

PMID- 23149121
TI  - Internet health information seeking is a team sport: analysis of the Pew Internet
      Survey.
AB  - BACKGROUND: Previous studies examining characteristics of Internet health
      information seekers do not distinguish between those who only seek for
      themselves, and surrogate seekers who look for health information for family or
      friends. Identifying the unique characteristics of surrogate seekers would help
      in developing Internet interventions that better support these information
      seekers. OBJECTIVE: To assess differences between self seekers versus those that
      act also as surrogate seekers. METHODS: We analyzed data from the cross-sectional
      Pew Internet and American Life Project November/December 2008 health survey. Our
      dependent variable was self-report of type of health information seeking
      (surrogate versus self seeking). Independent variables included demographics,
      health status, and caregiving. After bivariate comparisons, we then developed
      multivariable models using logistic regression to assess characteristics
      associated with surrogate seeking. RESULTS: Out of 1250 respondents who reported
      seeking health information online, 56% (N=705) reported being surrogate seekers.
      In multivariable models, compared with those who sought information for
      themselves only, surrogate seekers were more likely both married and a parent
      (OR=1.57, CI=1.08, 2.28), having good (OR=2.05, CI=1.34, 3.12) or excellent
      (OR=2.72, CI=1.70, 4.33) health status, being caregiver of an adult relative
      (OR=1.76, CI=1.34, 2.30), having someone close with a serious medical condition
      (OR=1.62, CI=1.21, 2.17) and having someone close to them facing a chronic
      illness (OR=1.55, CI=1.17, 2.04). CONCLUSIONS: Our findings provide evidence that
      information needs of surrogate seekers are not being met, specifically of
      caregivers. Additional research is needed to develop new functions that support
      surrogate seekers.

PMID- 23149122
TI  - Adopting and implementing nutrition guidelines in recreational facilities:
      tensions between public health and corporate profitability.
AB  - OBJECTIVE: Little is known about how public entities can partner with industry to
      achieve public health goals. We investigated industry's perspective of factors
      that influenced their adoption and implementation of voluntary, government-issued
      nutrition guidelines (Alberta Nutrition Guidelines for Children and Youth, ANGCY)
      in recreational facilities. DESIGN: In-depth semi-structured interviews were
      conducted. Data were analysed using directed content analysis. SETTING: Food
      services in recreational facilities. SUBJECTS: Seven managers from industry
      participated; five from companies that had adopted and implemented the ANGCY
      (adopters) in recreational facilities and two from companies that had not (non
      adopters). RESULTS: Industry views nutrition guidelines through the lens of
      profitability. Non-adopters were unwilling to implement the ANGCY for fear of
      sacrificing short-term profitability, whereas adopters adhered to them in an
      attempt to position themselves for long-term profitability. Adopters faced
      barriers including few resources, no training, complex guidelines, low
      availability of and demand for ANGCY-compliant products, competitive pressures
      and substantial declines in revenue. Managers believed widespread voluntary
      adoption of the ANGCY was unlikely without government incentives and/or a
      mandate, as the environmental context for voluntary action was poor. All managers
      supported government-mandated implementation of the ANGCY to level the playing
      field upon which companies compete. CONCLUSIONS: Public-private partnerships in
      recreational facilities can embrace public health goals in the short term,
      provided industry perceives potential for long-term financial gain. Widespread
      uptake of voluntary nutrition guidelines in this setting is unlikely, however, as
      market mechanisms do not encourage industry to sell and promote healthier
      options. Government legislation may therefore be warranted.

PMID- 23149123
TI  - Engineering an anaerobic metabolic regime in Pseudomonas putida KT2440 for the
      anoxic biodegradation of 1,3-dichloroprop-1-ene.
AB  - Pseudomonas putida KT2440, a microbial cell factory of reference for industrial
      whole-cell biocatalysis, is unable to support biochemical reactions that occur
      under anoxic conditions, limiting its utility for a large number of relevant
      biotransformations. Unlike (facultative) anaerobes, P. putida resorts to NADH
      oxidation via an oxic respiratory chain and completely lacks a true fermentation
      metabolism. Therefore, it cannot achieve the correct balances of energy and redox
      couples (i.e., ATP/ADP and NADH/NAD(+)) that are required to sustain an O(2)-free
      lifestyle. To overcome this state of affairs, the acetate kinase (ackA) gene of
      the facultative anaerobe Escherichia coli and the pyruvate decarboxylase (pdc)
      and alcohol dehydrogenase II (adhB) genes of the aerotolerant Zymomonas mobilis
      were knocked-in to a wild-type P. putida strain. Biochemical and genetic assays
      showed that conditional expression of the entire enzyme set allowed the
      engineered bacteria to adopt an anoxic regime that maintained considerable
      metabolic activity. The resulting strain was exploited as a host for the
      heterologous expression of a 1,3-dichloroprop-1-ene degradation pathway recruited
      from Pseudomonas pavonaceae 170, enabling the recombinants to degrade this
      recalcitrant chlorinated compound anoxically. These results underscore the value
      of P. putida as a versatile agent for biotransformations able to function at
      progressively lower redox statuses.

PMID- 23149125
TI  - Predictive value of optical coherence tomography in graft attachment after
      Descemet's membrane endothelial keratoplasty.
AB  - PURPOSE: To evaluate the predictive value of early anterior segment optical
      coherence tomography (AS-OCT) on graft adherence or detachment after Descemet's
      membrane endothelial keratoplasty (DMEK). DESIGN: Retrospective study of
      prospectively collected data at a tertiary referral center. PARTICIPANTS: A total
      of 87 eyes of 87 patients of a consecutive series of 142 DMEK surgeries. METHODS:
      Anterior segment OCT was performed within the first hour after DMEK and at 1
      week, 1 month, 3 months, and 6 months, and for each time interval detachments
      were classified as "none," <= 1/3 detachment, >1/3 detachment of the total graft
      surface area, or "complete" detachment. Throughout the study, no rebubbling
      procedures were performed. MAIN OUTCOME MEASURES: Graft adherence at various
      postoperative time intervals. RESULTS: One-hour AS-OCT scans were more accurate
      at predicting the final 6-month graft adherence status than those at 1 week or 1
      month. Grafts showing complete attachment or <1/3 detachment at 1 hour remained
      stable or improved in 73% of the cases at 1 week, 82% at 1 month, 86% at 3
      months, and 90% at 6 months. All grafts attached at 1 week remained attached at 6
      months. Graft detachments of >1/3 at 1 hour showed reattachment at 6 months in
      25% of the cases, whereas 67.5% of the cases showed a persistent detachment of
      >1/3 at 6 months and 12.5% showed a complete detachment. CONCLUSIONS: The 1-hour
      AS-OCT scan showed the best predictive value on 6-month graft adherence status.
      The combined information of the 1-hour and 1-week AS-OCT scans may facilitate
      decision making about surgical reintervention after DMEK.

PMID- 23149124
TI  - Silencing of the transcription factor STAT3 sensitizes lung cancer cells to DNA
      damaging drugs, but not to TNFalpha- and NK cytotoxicity.
AB  - Transcription factor STAT3 (Signal Transducers and Activators of Transcription 3)
      is persistently active in human tumors and may contribute to tumor progression.
      Inhibition of STAT3 expression/activity could be a good strategy to modulate
      tumor cell survival and responses to cancer chemotherapeutics or immune
      cytotoxicity. We silenced STAT3 expression in human A549 lung cancer cells to
      elucidate its role in cell survival and resistance to chemotherapeutics, TNFalpha
      and natural killer (NK)-mediated cytotoxicity. We demonstrate that STAT3 is not
      essential for basal survival and proliferation of A549 cancer cells. Stable
      silencing of STAT3 expression sensitized A549 cells to DNA damaging
      chemotherapeutics doxorubicin and cisplatin in a p53-independent manner.
      Sensitization to DNA damage-inducing chemotherapeutics could be due to down
      regulation of the Bcl-xL expression in STAT3 depleted cells. In contrast,
      knockdown of STAT3 in cancer cells did not modulate responses to TNFalpha and NK
      mediated cytotoxicity. We found that STAT3 depletion increased the NFkappaB
      activity likely providing the compensatory, pro-survival signal. The treatment
      with TNFalpha, but not doxorubicin, enhanced this effect. We conclude that STAT3
      is not crucial for the control of basal cell proliferation and survival of lung
      carcinoma cells but modulates susceptibility to DNA damaging chemotherapeutics by
      regulation of intrinsic pro-survival pathways.

PMID- 23149126
TI  - Variants in the VEGFA gene and treatment outcome after anti-VEGF treatment for
      neovascular age-related macular degeneration.
AB  - PURPOSE: To determine the association of genetic variants of the VEGFA gene with
      outcome of anti-vascular endothelial growth factor (VEGF) treatment in
      neovascular age-related macular degeneration (AMD). DESIGN: A prospective cohort
      study. PARTICIPANTS: We included 201 consecutive patients receiving anti-VEGF
      injections for neovascular AMD. METHODS: Patients were followed over 12 months.
      They were treated with 3 initial monthly ranibizumab or bevacizumab injections.
      Thereafter, the decision to retreat was made by clinicians at each follow-up
      visit on the basis of retreatment criteria. Seven tagged single nucleotide
      polymorphisms (tSNPs) in the VEGFA gene were selected and examined. Multivariate
      data analysis was used to determine the role of each tSNP in treatment outcome.
      MAIN OUTCOME MEASURES: The influence of selected VEGFA tSNPs on visual acuity
      (VA) outcome at 6 months. RESULTS: Mean baseline VA was 51+/-17 Early Treatment
      Diabetic Retinopathy Study (ETDRS) letter scores. Overall, the mean change in VA
      from baseline was +6.5+/-12, +4.4+/-13.4, and +2.3+/-14.6 letters at 3, 6, and 12
      months, respectively. The tSNP rs3025000 was the only SNP significantly
      associated (P<1 * 10(-4)) with visual outcome at 6 months with multiple
      correction. The presence of the T allele (TC or TT genotypes) at this tSNP
      predicted a better outcome of +7 letters at 6 months compared with the CC
      genotype. In a subgroup analysis, presence of the T allele predicted a
      significantly higher chance of the patients belonging to the responder group
      (gain of >=5 letters from baseline) after 3, 6, and 12 months treatment (odds
      ratio, 2.7, 3.5, and 2.4; 95% confidence interval, 1.46-5.07, 1.82-6.71, and 1.27
      4.57, respectively) than any other outcome group. CONCLUSIONS: Pharmacogenetic
      association with anti-VEGF treatments may influence the visual outcomes in
      neovascular AMD. In patients with the T allele in tSNP rs3025000, there was a
      significantly better visual outcome at 6 months and a greater chance of the
      patients belonging to the responder group with anti-VEGF treatment at 3, 6, and
      12 months. The VA outcomes of patients harboring the T allele at SNP rs3025000
      were comparable with those of the pivotal clinical trials but with fewer
      injections, making the treatment perhaps more cost effective in certain subgroups
      of patients. FINANCIAL DISCLOSURE(S): The authors have no proprietary or
      commercial interest in any of the materials discussed in this article.

PMID- 23149127
TI  - Vision impairment and major causes of vision loss impacts on vision-specific
      functioning independent of socioeconomic factors.
AB  - PURPOSE: To quantify the eye disease-specific impact of unilateral and bilateral
      vision impairment (VI) on vision-specific functioning (VF). DESIGN: The Singapore
      Indian Eye population-based study. PARTICIPANTS: Ethnic Indians older than 40
      years of age living in Singapore. METHODS: Participants underwent standardized
      ophthalmic assessments for VI and blindness, defined using presenting visual
      acuity (United States definition). Sociodemographic data were recorded using a
      standardized questionnaire. Rasch analysis was used to validate the Visual
      Function Index 11 and to determine its psychometric properties. The major causes
      of VI (i.e., cataract, refractive error, age-related macular degeneration,
      diabetic retinopathy [DR], and glaucoma) were determined by ophthalmologists on
      examination. Multivariate linear regression analysis was performed to assess the
      impact of VI on the overall VF Rasch score. MAIN OUTCOME MEASURES: Vision
      specific functioning. RESULTS: Three thousand three hundred ninety-six persons
      were analyzed. Participants with VI had a systematic reduction in VF score
      compared with those with normal vision in both eyes, ranging from -11.2% normal
      vision in one eye and low vision in the other eye (95% confidence interval [CI], 
      12.2% to -10.3%; P<0.001), to -12.7% blindness in one eye and normal vision in
      the other eye (CI, -15.1% to -10.4%; P<0.001), to -19.4% low vision in both eyes
      (CI, -20.8% to -18.1%; P<0.001), to -52.9% blindness in one eye and low vision in
      other eye (CI, -55.3% to -50.4%; P<0.001), to -77.2% blindness in both eyes (CI, 
      82.4% to 72.0%; P<0.001). The impact of VI on VF score varied across different
      major causes of vision loss, regardless of socioeconomic factors. Vision
      impairment attributed to cataract in one or both eyes had a significant decrease
      in VF score by 17.7% and 22.3%, respectively, compared with those with normal
      vision in both eyes (P<0.001). The impact of unilateral and bilateral VI on VF
      score was greater in participants with glaucoma (32.2% in unilateral cases and
      35.9% in bilateral cases; P<0.001) and DR (29.4% in unilateral cases and 33.3% in
      bilateral cases; P<0.001). CONCLUSIONS: Vision impairment and major age-related
      eye diseases such as cataract, DR, and glaucoma are associated significantly with
      worse deterioration in VF, regardless of education level, literacy adequacy, or
      immigration pattern. Glaucoma and DR seemed to have a greater negative impact on
      VF score compared with cataract. This study highlights the importance of disease
      specific interventions in reducing the adverse impact of VI on daily activities.

PMID- 23149128
TI  - Benign orbital apex tumors treated with multisession gamma knife radiosurgery.
AB  - OBJECTIVE: The orbital apex is an important anatomic landmark that hosts numerous
      critical neurovascular structures. Tumor resection performed at this complex
      region poses a therapeutic challenge to orbital surgeons and often is associated
      with significant visual morbidity. This article reports the efficacy and safety
      of multisession gamma knife radiosurgery (GKRS) in benign, well-circumscribed
      tumors located at the orbital apex. DESIGN: Retrospective interventional case
      series. PARTICIPANTS: Five patients with visual disturbances resulting from a
      benign, well-circumscribed orbital apex tumor (3 cases of cavernous hemangioma
      and 2 cases of schwannoma). METHODS: Each patient treated with GKRS with a total
      radiation dose of 20 Gy in 4 sessions (5 Gy in each session with an isodose line
      of 50%) delivered to the tumor margin. MAIN OUTCOME MEASURES: Best-corrected
      visual acuity, visual field changes, orbital imaging, tumor growth control, and
      side effects of radiation. RESULTS: All patients demonstrated improvement in
      visual acuity, pupillary responses, color vision, and visual field. Tumor
      shrinkage was observed in all patients and remained stable until the last follow
      up. No adverse events were noted during or after the radiosurgery. None of the
      patients experienced any radiation-related ocular morbidity. CONCLUSIONS: From
      this experience, multisession GKRS seems to be an effective management strategy
      to treat solitary, benign, well-circumscribed orbital apex tumors.

PMID- 23149129
TI  - Progression pattern of initial parafoveal scotomas in glaucoma.
AB  - OBJECTIVE: To characterize the progression pattern of initial parafoveal scotomas
      (IPFSs) using cross-sectional and longitudinal 10-2 visual field (VF) data.
      DESIGN: Retrospective, observational study. PARTICIPANTS: Glaucoma patients with
      an IPFS in either hemifield based on 2 reliable 24-2 Swedish interactive
      threshold algorithm standard VFs (>=3 adjacent points with P<0.05 within the
      central 10 degrees  of fixation, 1 point or more with P<0.01 lying at the
      innermost paracentral points, and no scotoma outside the central 10 degrees ) and
      at least 2 10-2 VFs (first and last VFs 1 year or more apart). METHODS: To
      simulate a cohort with an extended follow-up, eyes with an IPFS were divided into
      subgroups based on the severity of glaucoma using their 10-2 VF pattern standard
      deviation (PSD). Cross-sectional data were used to create an average pattern
      deviation map that was generated by averaging pattern deviation map values of 10
      2 VF point-by-point within each subgroup. Longitudinal data (eyes with 5 or more
      10-2 VFs) was used to perform pointwise linear regression analysis of pattern
      deviation values. Patterns of IPFS progression were identified from these cross
      sectional and longitudinal assessments. MAIN OUTCOME MEASURES: Average pattern
      deviation maps (cross-sectional) and maps of progression rates (longitudinal) in
      different disease severity subgroups. RESULTS: Eighty eyes (80 patients) and 40
      eyes (40 patients) with an IPFS were included for cross-sectional and
      longitudinal analyses, respectively. The mean age +/- standard deviation, 24-2 VF
      mean deviation, and 24-2 VF PSD for all eyes were 63+/-10 years, -3.27+/-2.18 dB,
      and 5.46+/-2.40 dB, respectively. Based on maps generated in both cross-sectional
      and longitudinal analyses, IPFS in the superior hemifield had an arcuate pattern
      initially that later deepened approximately 3 degrees  to 5 degrees  above
      fixation. The scotoma then elongated toward the physiologic blind spot and spread
      toward the nasal periphery, sparing the area corresponding to the papillomacular
      bundle. The IPFS in the inferior hemifield had a similar pattern, but was
      slightly farther from fixation. CONCLUSIONS: Superior and inferior IPFS have a
      similar characteristic pattern of progression, although the latter tend to be
      farther from fixation. Understanding these patterns should help in the management
      of such patients and in improving VF testing algorithms.

PMID- 23149130
TI  - Transcranial alternating current stimulation reduces symptoms in intractable
      idiopathic cervical dystonia: a case study.
AB  - Idiopathic cervical dystonia (ICD) is a movement disorder often resulting in
      profound disability and pain. Treatment options include oral medications or other
      invasive procedures, whereas intractable ICD has been shown to respond to
      invasive (deep) brain stimulation. In the present blinded, placebo-controlled
      case study, transcranial direct current stimulation (tDCS) and transcranial
      alternating current stimulation (tACS) has been applied to a 54-year old patient
      with intractable ICD. Results showed that 15 Hz tACS had both immediate and
      cumulative effects in dystonic symptom reduction, with a 54% reduction in the
      Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) total score, and a
      75% in the TWSTRS Pain Scale. These effects were persistent at 30-days follow-up.
      This is the first report to demonstrate a significant and lasting therapeutic
      effect of non-invasive electrical brain stimulation in dystonia.

PMID- 23149131
TI  - Theta-gamma coupling during a working memory task as compared to a simple
      vigilance task.
AB  - Theta-gamma coupling (TGC) is known to reflect working memory processes, but it
      is unclear whether TGC as measured by scalp electroencephalography (EEG) reflects
      working memory processes or nonspecific attentional processes. In this study, we
      examined the degree of TGC during a visuo-spatial working memory task (2-back
      task) vs. a simple vigilance task in 13 young participants. During the working
      memory task, TGC increased in the frontal area at approximately 40 Hz. In
      addition, TGC was also significantly different at high-gamma frequency despite no
      differences in gamma power between the two tasks, and a correlation between TGC
      only during the working memory task and hit rate was observed. These results
      suggest that TGC reflects working memory processes and may be a useful bio
      physiological marker of working memory.

PMID- 23149132
TI  - Total CSF alpha-synuclein is lower in de novo Parkinson patients than in healthy
      subjects.
AB  - Several studies demonstrated reduced CSF alpha-synuclein values in patients with
      advanced Parkinson's disease (PD). Values in drug-naive PD subjects and healthy
      controls (HC) have not yet been reported. We measured CSF values including alpha
      synuclein in a cohort of 78 previously untreated PD patients and 48 HC subjects.
      Measurements of total alpha-synuclein concentrations were performed using two
      independently operated immunoassays, i.e., one academia-based and previously
      validated (ELISA 1), the other industry-based, renewable and commercially
      available (ELISA 2). Mean values for CSF alpha-synuclein were significantly lower
      in de novo PD patients when compared to HC subjects, as demonstrated by both
      assays (ELISA 1, p=0.049; ELISA 2, p=0.005; combined, p=0.002). Using the
      renewable ELISA 2, CSF alpha-synuclein concentrations of 1884.31 pg/ml or less
      showed a sensitivity of 0.91 and a specificity of 0.25 for the diagnosis of
      Parkinson's disease. The corresponding area-under-the-curve value was 0.65
      (confidence interval, 0.554-0.750), which was statistically significant
      (p=0.004). Total CSF alpha-synuclein is reduced early in the course of
      Parkinson's disease, as measured by two independent ELISA platforms at the time
      of enrolment, and this reduction appears independent from drug treatment. Follow
      up investigations will determine the usefulness of CSF alpha-synuclein values as
      markers of progression in individual subjects.

PMID- 23149134
TI  - Specialist nursing care enables more people at end of life to die at home and
      reduces hospital treatment, study finds.

PMID- 23149133
TI  - Modulation of paraventricular firing rate by secretin in vivo.
AB  - The paraventricular nucleus (PVN) of hypothalamus is a major integrative center
      in homeostatic control. Morphological studies have revealed a high level of
      secretin and secretin receptor expression in the PVN. To investigate the direct
      electrophysiological effects of secretin in the PVN, in vivo extracellular
      recordings were performed in the present study. In 24 out of the 46
      paraventricular neurons, micro-pressure ejection of secretin increased the firing
      rate from 3.07+/-0.43 Hz to 4.86+/-0.70 Hz. In another 8 out of the 46
      paraventricular neurons, secretin decreased the firing rate from 2.61+/-0.46 Hz
      to 1.41+/-0.25 Hz. In the remaining 14 paraventricular neurons, secretin did not
      alter the firing rate significantly. The present findings provided direct
      electrophysiological evidence for the possible functions of secretin in the PVN.

PMID- 23149135
TI  - Preparation of A2 reverse grouping cells from A2B red blood cells by alpha
      galactosidase.

PMID- 23149136
TI  - Six hours of resting platelet concentrates stored at 22-24 oC for 48 hours in
      permeable bags preserved pH, swirling and lactate dehydrogenase better and caused
      less platelet activation.
AB  - BACKGROUND: During transportation, platelet concentrates (PC) usually undergo a
      long period without agitation. Whether this interruption improves quality and
      viability or, contrariwise, has deleterious effects on PC stored for 48 hours (h)
      is unknown. The aim of this study was to investigate the effects of metabolic
      resting (6 h of interruption of agitation) vs continue agitation of PC stored for
      48 h in the blood bank of Tehran. MATERIALS AND METHODS: PC were prepared from
      platelet-rich plasma and stored in permeable bags in a shaker/incubator for 42 h
      at room temperature (20-24 oC). Then, simply by stopping the agitator, the PC
      remained stationary ("resting") without agitation for 6 h (WCA6h), prior to
      transfusion. In vitro measurements of platelet quality were carried out just
      after completion of the resting period and the results were compared with those
      of PC continuously agitated in the same day (designated as the control group,
      CA6h). The in vitro variables measured were swirling, ristocetin-induced
      aggregation (GPIb-related function), lactate dehydrogenase (LDH) concentration,
      platelet factor 4 (PF4) release and P-selectin expression (activation markers).
      RESULTS: The mean platelet counts of the control group (CA6h) and rested (WCA6h)
      PC were not statistically different (P =0.548). Likewise, the mean pH values were
      not significantly different: WCA6h (7.16 +/- 0.08) and CA6h (7.22 +/- 0.16) (P
      =0.300). Although ristocetin-induced aggregation did not differ significantly
      between CA6h (79.2 +/- 4.4) and WCA6h (66.65 +/- 28.55) (P =0.186), WCA6h showed
      significantly less PFA release (P =0.015) and lower P-selectin expression (P
      =0.006). CONCLUSIONS: We observed that PC stored under agitation for 42 h at 22
      24 oC in permeable bags and then rested for 6 h had better preserved pH, swirling
      and LDH and less platelet activation then PC kept under continuous agitation for
      the whole 48 h storage period.

PMID- 23149137
TI  - Limited utility of algorithms predicting blood transfusions.
AB  - BACKGROUND: Prediction of transfusion is presumed to reduce wastage rates in pre
      operative autologus blood donation (PABD) and unnecessary providing and cross
      matching in allogeneic transfusion. The clinical utility of published algorithms
      in predicting transfusions was analysed. MATERIALS AND METHODS: In a cohort of
      195 patients undergoing total hip arthroplasty, after PABD, expected transfusion
      needs were predicted with two published algorithms (A and B). The algorithms were
      then compared to actual transfusions. Assumptions and formulae of these
      algorithms were varied in an attempt to improve their prognostic utility.
      RESULTS: The optimal variation of A resulted in allogeneic transfusions (PABD
      setting) or uncross-matched transfusions (allogeneic setting) of 27.3%, and a
      wastage rate of autologous units or unnecessary cross-matching of 73.8%, compared
      to 33.3% and 76.6%, respectively, for the original algorithm. The original
      version of algorithm B resulted in (allogeneic) transfusions of 78.8%, and a
      wastage rate or unnecessary cross-matching of 46.2%. The former could be improved
      by a variation of the algorithm to 69.7%. Comparing the optimal variations of
      both algorithms, the more elaborate algorithm A reduced overall transfusion risk
      significantly better (P =0.001). The two algorithms were not statistically
      different in reducing resource consumption (P =0.09). DISCUSSION: Although the
      prognostic utility of algorithm A was significantly better for reducing overall
      transfusion risk, both algorithms were unable to meaningfully identify patients
      who would benefit from PABD or cross-matching. The algorithms could not increase
      the percentage of PABD patients transfused, or the percentage of cross-matched
      patients transfused in the allogeneic setting. Furthermore, they could neither
      reduce transfusion risk nor resource consumption.

PMID- 23149138
TI  - Evaluation of ABO blood groups as a risk factor for myocardial infarction.

PMID- 23149139
TI  - "Transfusion indication RBC (PBM-02)": gap analysis of a Joint Commission Patient
      Blood Management Performance Measure at a community hospital.
AB  - BACKGROUND: The Joint Commission accredits health care organisations in the USA
      as a prerequisite for licensure. In 2011, TJC published seven Patient Blood
      Management Performance Measures to improve the safety and quality of care. These
      Measures will provide hospital-specific information about clinical performance.
      MATERIALS AND METHODS: Of the seven TJC PBM Performance Measures, we decided to
      evaluate PBM-02, "Transfusion indication RBC", at our hospital. Blood transfusion
      orders were collected from May 2 to August 2, 2011 and the data analysed.
      RESULTS: Of the 724 consecutive red blood cell transfusion orders, 694 (96%)
      documented both clinical indication and pre-transfusion haemoglobin/haematocrit
      results. The leading transfusion indication (47% of total) was "high risk
      patients with pre-transfusion Hb of <9 g/dL". The majority (72%) of non-actively
      bleeding patients received a single unit of blood as recommended by our
      transfusion guidelines. However, 70% of these patients went on to receive
      additional units and 21% of the initial orders were placed for two or more units.
      Patients with active bleeding and special circumstances accounted for 17% and 4%
      of the transfusions, respectively. Our blood utilisation did not change by
      introducing the single-unit transfusion policy. DISCUSSION: The majority (96%) of
      the transfusion orders met The Joint Commission criteria by providing both
      transfusion indication and pre-transfusion Hb and/or Hct values. Our transfusion
      guidelines recommend single-unit red blood cell transfusions with reassessment of
      the patient after each transfusion for need to receive more blood. Although most
      (72%) initial orders followed our transfusion guidelines, 70% of patients who
      received a single unit initially went on to receive more blood (some in excess of
      10 units). Our objective data may be helpful in evaluating blood ordering
      practices at our hospital and in identifying specific clinical services for
      review.

PMID- 23149140
TI  - The effect of treatment with alpha-glycosidases from Bacteroides fragilis on the
      survival of rat erythrocytes in the circulation.
AB  - BACKGROUND: It has been demonstrated recently that alpha1,3-galactosidase from
      Bacteroides fragilis can efficiently convert human group B red blood cells (RBC)
      to group O cells. In addition, in vitro data indicated that the enzymatic
      conversion process did not affect the physiological or metabolic parameters of
      the RBC. The aim of this study was to investigate the lifespan of enzyme- treated
      RBC in vivo in the circulation. MATERIALS AND METHODS: This was an experimental,
      randomised study. The rat was selected as the experimental subject because it
      expresses alpha-1,3galactosyl on its RBC. The efficiency of Galalpha1,3Gal
      epitope removal from RBC treated with alpha1,3-galactosidase was tested before
      the transfusion experiment to track the survival of RBC in the circulation. The
      animals were divided into three groups and injected via the tail vein with
      native, mock-treated or enzyme-treated RBC labelled with fluorescein
      isothiocyanate. The survival rates of the fluorescently labelled RBC were
      monitored by flow cytometry. RESULTS: Flow cytometry showed that alpha
      galactosidase (0.02 mg/mL for RBC with a haematocrit of 30%) efficiently removed
      Galalpha1,3Gal epitopes from rat erythrocytes, although small amounts of
      remaining Galalpha1,3Gal epitopes were still detected. The in vivo data
      demonstrated that the half-life of enzyme-treated RBC was a little shorter than
      that of native RBC. However, the 24-hour survival fractions of native, mock
      treated and enzyme-treated RBC were virtually identical. Most importantly, the
      enzyme-treated RBC, like the native RBC, were still detectable 35 days after
      transfusion. DISCUSSION: Our results indicate that alpha-glycosidase treatment
      had little effect on the in vivo survival kinetics of RBC. These data add further
      support to the feasibility of translating enzymatic conversion technology into
      clinical practice.

PMID- 23149141
TI  - The use of telemedicine in Italian Blood Banks: a nationwide survey.
AB  - BACKGROUND: Telemedicine is defined as the use of electronic information and
      communication technologies to provide health care between distant people. Many
      activities in transfusion medicine could benefit from the application of
      telemedicine. To map the spread of the use of telemedicine in transfusion
      medicine in Italy, the Italian Society of Transfusion Medicine and
      Immunohaematology (SIMTI) performed a nationwide survey: the results are
      presented in this paper. MATERIALS AND METHODS: A survey, dealing with different
      aspects of the use of telemedicine, was performed by sending a questionnaire to
      280 Italian Blood Centres. The survey was designed to evaluate the diffusion of
      telemedicine and the features of the systems, with special attention to the
      systems' safety and legal adequacy. One section of the questionnaire was designed
      to identify the features of the systems considered essential by the respondents.
      RESULTS: Out of 280 Blood Services contacted, 196 (70%) filled in at least one of
      the questions of the online questionnaire. Globally the use of some form of
      telemedicine was reported by 70% of the respondents. Telemedicine is used for
      remote validation of laboratory tests by 32% of the Centres that responded, for
      remote biological validation of blood units by 34% and for assignment of blood
      components by 29%. Less frequently, telemedicine is used to control electronic
      refrigerators, for electronic blood requests and for bed-side identification of
      patients. DISCUSSION: The use of telemedicine is widespread in Italian Blood
      Services. There appears to be some heterogeneity between structures with regards
      to the evaluation of the systems' safety and their legal adequacy. No
      telemedicine system should be introduced into practice until it has proven to
      have the same standards of safety as the corresponding "on site" activity.

PMID- 23149142
TI  - Thrombocytopenia in patients with patent ductus arteriosus after transcatheter
      closure: perilous complication or harmless incidental finding?

PMID- 23149143
TI  - Assessment of leucoreduction of sickle cell trait blood: quality of the filtered
      product.
AB  - BACKGROUND: With the implementation of universal leucoreduction of blood
      components in several industrialised countries, the problems associated with
      leucocyte filtration of sickle cell trait blood have been reconsidered. In this
      study, we assessed the use of high performance filters for leucoreduction of
      packed red blood cells donated from subjects with sickle cell trait and evaluated
      the incidence and recurrence of altered red blood cell filterability. MATERIALS
      AND METHODS: Twenty-one volunteer donors with HbAS were compared to 21 donors
      with HbAA selected at random. The main parameters analysed were residual white
      blood cell count and post-filtration haemolysis. Filtration times, flow, volume
      and haemoglobin loss of the packed red blood cells were also determined. RESULTS:
      In all, 33% of HbAS red blood cell units with slow flow and prolonged filtration
      time had high residual white blood cell counts. In 7.7% of cases, despite flow
      through the filter, the units were not leucoreduced properly. Haemoglobin and
      volume loss were significantly greater in the slow filtration group. Significant
      post-filtration haemolysis was present in half of the units with high residual
      white blood cell counts. DISCUSSION: Despite the development of new technology
      for filtration, the problem of filterability of blood from donors with sickle
      cell trait is not yet resolved. Altered filterability of blood from sickle cell
      trait donors cannot be predicted from the donors' characteristics and recurrence
      of the problem is not observed between donations. Screening blood donors for
      sickle cell trait to ensure the safety and quality of blood products for
      transfusion does, therefore, remain a relevant issue.

PMID- 23149144
TI  - Turning severe into moderate haemophilia by prophylaxis: are we reaching our
      goal?
AB  - BACKGROUND: Since the introduction of prophylaxis, physicians have tried to
      convert the clinical phenotype of severe haemophilia (SH) into that of moderate
      haemophilia (MH), but the outcome of patients with SH has never been compared to
      that of patients with MH. MATERIAL AND METHODS: The outcome of 80 patients with
      SH on long-term, intermediate dose prophylaxis was compared to that of 40
      patients with MH in a single-centre study. Data on treatment history, activities
      (assessed by the IPAQ and HAL), quality of life (assessed by the SF-36 and EQ5D),
      and 5-year bleeding and clotting factor consumption were collected for patients
      born between 1970-1995. RESULTS: The median age of the patients was 24 years (IQR
      18-30). All patients with SH received long-term prophylaxis, which was started at
      a median age of 4.8 years (IQR 3.2-6.2). Among the patients with MH, ten (25%)
      received prophylaxis, starting at a median age of 10.8 years (IQR 3.8-13.8). The
      annual number of bleeds, including joint bleeds, was significantly higher in
      patients with SH (median 2.0 joint bleeds/year, IQR =0.8-3.7) than in patients
      with MH (median 0.8 joint bleeds/year, IQR =0-1.2). Due to greater use of
      prophylaxis, the annual clotting factor consumption of SH patients (median 2,120
      IU/kg; IQR 1,514-2,768), was higher than that of MH patients (median 133 IU/kg;
      IQR 49-468). Patients with SH showed slightly but significantly more loss of
      clinical function (assessed by the Haemophilia Joint Health Score): a median of 8
      points (IQR 3-15) vs a median of 2 points, IQR 0-6). Quality of life, as measured
      by the SF-36, EQ5D and physical activity, was similar between patients with
      disease of different severity, as well as compared to that of the general
      population. DISCUSSION: When comparing unselected cohorts, the bleeding pattern
      of patients with SH does not appear to be fully converted to that of the milder
      bleeding pattern of MH by long-term, intermediate-dose prophylaxis, although
      activities and quality of life were similar.

PMID- 23149146
TI  - Trends in the landscape of artificial urinary sphincter implantation in men and
      women in France over the past decade.

PMID- 23149145
TI  - The cost of post-operative shed blood salvage after total knee arthroplasty: an
      analysis of 1,093 consecutive procedures.
AB  - BACKGROUND: Requirements for allogeneic red cell transfusion after total knee
      arthroplasty are still high (20-50%), and salvage and reinfusion of unwashed,
      filtered post-operative shed blood is an established method for reducing
      transfusion requirements following this operation. We performed a cost analysis
      to ascertain whether this alternative is likely to be cost-effective. MATERIALS
      AND METHODS: Data from 1,093 consecutive primary total knee arthroplasties,
      managed with (reinfusion group, n=763) or without reinfusion of unwashed salvaged
      blood (control group, n=330), were retrospectively reviewed. The costs of low
      vacuum drains, shed blood collection canisters (Bellovac ABT, Wellspect
      HealthCare and ConstaVac CBC II, Stryker), shed blood reinfusion, acquisition and
      transfusion of allogeneic red cell concentrate, haemoglobin measurements, and
      prolonged length of hospital stay were used for the blood management cost
      analysis. RESULTS: Patients in the reinfusion group received 152+/-64 mL of red
      blood cells from postoperatively salvaged blood, without clinically relevant
      incidents, and showed a lower allogeneic transfusion rate (24.5% vs. 8.5%, for
      the control and reinfusion groups, respectively; p =0.001). There were no
      differences in post-operative infection rates. Patients receiving allogeneic
      transfusions stayed in hospital longer (+1.9 days [95% CI: 1.2 to 2.6]). As
      reinfusion of unwashed salvaged blood reduced the allogeneic transfusion rate,
      both reinfusion systems may provide net savings in different cost scenarios (?
      4.6 to ? 106/patient for Bellovac ABT, and ? -51.9 to ? 49.9/patient for
      ConstaVac CBCII). DISCUSSION: Return of unwashed salvaged blood after total knee
      arthroplasty seems to save costs in patients with pre-operative haemoglobin
      between 12 and 15 g/dL. It is not cost-saving in patients with a pre-operative
      haemoglobin >15 g/dL, whereas in those with a pre-operative haemoglobin <12 g/dL,
      although cost-saving, its efficacy could be increased by associating some other
      blood-saving method.

PMID- 23149147
TI  - Reply to Henk G. van der Poel, Tessa Buckle and Renato Valdes Olmos' letter to
      the editor re: Steven Joniau, Laura Van den Bergh, Evelyne Lerut, et al. Mapping
      of pelvic lymph node metastases in prostate cancer. Eur Urol. In press.
      http://dx.doi.org/10.1016/j.eururo.2012.06.057.

PMID- 23149148
TI  - Adipose-derived stem cells for the treatment of Peyronie's disease?

PMID- 23149149
TI  - Meta-analyses indicate associations between neuroendocrine activation,
      deactivation in neurotrophic and neuroimaging markers in depression after stroke.
AB  - BACKGROUND: The association between stroke and depression is well established and
      has been suggested to be bidirectional. Systemic immune activation, hypothalamic
      pituitary-adrenal axis hyperactivity, physiologic changes in the perfusion of
      blood vessels, the downregulation of neurotrophic factors, and apoptosis and
      necrosis of neuronal, glial, and endothelial cells have been frequently
      implicated in this relationship. A better understanding of the biology of
      poststroke depression could be important for enhancing clinical management. We
      review the currently available biologic markers of stroke-associated depressive
      illness (i.e., neurophysiologic, neuroendocrine, immunologic, and neuroimaging
      markers as well as neurotrophic factors). METHODS: Search strategies included the
      electronic databases PubMed, PsycINFO, EMBASE, CINAHL, the Cochrane Library, and
      Proquest Dissertations (all records through June 2012), the reference lists of
      retrieved articles, the reference list of relevant reviews, and direct contact
      with authors of retrieved articles for any additional unpublished data. RESULTS:
      Thirty-three papers fulfilled the criteria for inclusion. We detected moderate
      effects for high postdexamethasone cortisol levels (odds ratio [OR] 3.28; 95%
      confidence interval [CI] 1.28-8.39; P = .01), lower serum brain-derived
      neurotrophic factor levels (standardised mean difference [SMD] -0.52; 95% CI 
      0.84 to -0.21; P = .001), smaller amygdala volumes (SMD -0.45; 95% CI -0.89 to 
      0.02; P = .04), and a small effect for overall brain perfusion reduction (SMD 
      0.35; 95% CI -0.64 to -0.06; P = .02), respectively, to poststroke depression.
      CONCLUSIONS: Cortisol-lowering therapies and those that increase blood flow and
      neurotrophic factors represent promising novel therapeutics for depression
      subtypes and may reduce the risk of depression in stroke patients.

PMID- 23149150
TI  - Nationwide patterns of hospitalization after transient ischemic attack.
AB  - BACKGROUND: Little is known about nationwide patterns of hospitalization after
      transient ischemic attack (TIA). METHODS: In a nationally representative sample
      of Emergency Department (ED) visits included in the National Hospital Ambulatory
      Medical Care Survey (NHAMCS) from 1997 through 2008, we estimated rates of
      hospitalization among patients with a primary ED diagnosis of TIA (International
      Classification of Diseases, 9th Revision (ICD-9), code 435). We used multiple
      logistic regression analysis to examine the association between hospitalization
      and demographic characteristics, geographic region, year of the visit, time of
      the visit, and markers of stroke risk. RESULTS: On the basis of 782 cases of TIA
      sampled by the NHAMCS, 57% (95% confidence interval [CI], 52%-61%) of patients
      with TIA nationwide were hospitalized. A higher proportion of patients was
      hospitalized in 2003 to 2008 (62%; 95% CI, 56%-68%) than in 1997 to 2002 (52%;
      95% CI, 46%-58%; P = .02). Compared with the US Northeast, patients were less
      likely to be hospitalized in the Midwest (odds ratio [OR], 0.5; 95% CI, .3-.9),
      the South (OR, 0.3; 95% CI, .2-.5), or the West (OR, 0.2; 95% CI, .1-.4).
      Compared with white patients, hospitalization was more likely among patients who
      were black (OR, 2.4; 95% CI, 1.3-4.5), Hispanic (OR, 3.8; 95% CI, 1.4-10.2), or
      of other races (OR, 3.5; 95% CI, 1.3-9.6). Patients with Medicaid were admitted
      less often than those with private insurance (OR, 0.3; 95% CI, .2-.8).
      CONCLUSIONS: Nationwide patterns of hospitalization after TIA show significant
      regional and demographic variation. These results may provide a useful roadmap
      for efforts to improve systems of care for TIA across the country.

PMID- 23149151
TI  - Factors related to occurrence and distribution of selected bacterial and
      protozoan pathogens in Pennsylvania streams.
AB  - The occurrence and distribution of fecal indicator bacteria (FIB) and bacterial
      and protozoan pathogens are controlled by diverse factors. To investigate these
      factors in Pennsylvania streams, 217 samples were collected quarterly from a 27
      station water-quality monitoring network from July 2007 through August 2009.
      Samples were analyzed for concentrations of Escherichia coli (EC) and enterococci
      (ENT) indicator bacteria, concentrations of Cryptosporidium oocysts and Giardia
      cysts, and the presence of four genes related to pathogenic types of EC (eaeA,
      stx2, stx1, rfb(O157)) plus three microbial source tracking (MST) gene markers
      that are also associated with pathogenic ENT and EC (esp, LTIIa, STII). Water
      samples were concurrently analyzed for basic water chemistry, physical measures
      of water quality, nutrients, metals, and a suite of 79 organic compounds that
      included hormones, pharmaceuticals, and antibiotics. For each sample location,
      stream discharge was measured by using standardized methods at the time of sample
      collection, and ancillary sample site information, such as land use and
      geological characteristics, was compiled. Samples exceeding recreational water
      quality criteria were more likely to contain all measured pathogen genes but not
      Cryptosporidium or Giardia (oo)cysts. FIB and Giardia density and frequency of
      eaeA gene occurrence were significantly related to season. When discharge at a
      sampling location was high (>75th percentile of daily mean discharge), there were
      greater densities of FIB and Giardia, and the stx2, rfb(O157), STII, and esp
      genes were found more frequently than at other discharge conditions. Giardia
      occurrence was likely related to nonpoint sources, which are highly influential
      during seasonal overland transport resulting from snowmelt and elevated
      precipitation in late winter and spring in Pennsylvania. When MST markers of
      human, swine, or bovine origin were present, samples more frequently carried the
      eaeA, stx2, stx1, and rfb(O157) genes, but no genes were related exclusively to
      an individual MST marker. The human source pharmaceuticals (HSPs) acetaminophen
      and caffeine were correlated with Giardia, and the presence of HSPs proved to be
      more useful than MST markers in distinguishing the occurrence of Giardia. The
      HSPs caffeine and carbamazepine were correlated with the sum total of pathogen
      genes detected in a sample, demonstrating the value of using HSPs as an indicator
      of fecally derived pathogens. Sites influenced by urban land use with less forest
      were more likely to have greater FIB and Giardia densities and sum of the array
      of pathogen genes. Sites dominated by shallow carbonate bedrock in the upstream
      catchment were likely to have greater FIB densities and higher sum totals of
      pathogen genes but no correlation with Giardia detection. Our study provides a
      range of specific environmental, chemical, geologic, and land-use variables
      related to occurrence and distribution of FIB and selected bacterial and
      protozoan pathogens in Pennsylvania streams. The information presented could be
      useful for resource managers in understanding bacterial and protozoan pathogen
      occurrence and their relation to fecal indicator bacteria in similar settings.

PMID- 23149152
TI  - Influences of food hardness on the particle size distribution of food boluses.
AB  - OBJECTIVES: Bolus swallowing or deglutition is a vital oral action which
      transports orally processed food from the oral cavity to the stomach for further
      digestion. Swallowing is routine to most health individuals, but it could be
      highly hazardous to many elderly and dysphagia patients. In order to provide
      proper food for safe consumption by these disadvantaged populations, a
      fundamental understanding of how bolus swallowing is triggered and is based on
      what criteria is urgently needed. Main objective of this work was to understand
      the physical properties of food boluses, in particular the bolus particle size
      distribution in relation to the hardness of the food. METHODS: Food samples were
      chewed in free style by subjects and boluses were expectorated when subjects felt
      they were ready to be swallowed. Altogether seven different types of food were
      used and 10 health subjects participated in this study. Bolus particles were
      carefully washed and spread out on a flat surface. Images of bolus particles were
      taken using a digital camera and analysed using Image Pro Plus software for
      particle size quantification. Food hardness was measured using a Texture Analyser
      by a puncture test. RESULTS: It was observed that bolus particle size decreased
      with the increase of food hardness. The correlation between the two properties
      can be described by a power-law relationship. This relationship was also found
      applicable to literature results reported by Peyron et al. and Jalabert-Malbos et
      al. CONCLUSIONS: Food hardness has a direct influence on its bolus particle size.
      The harder the food, the smaller the bolus particle size.

PMID- 23149153
TI  - Recovery of mutans streptococci on MSB, SB-20 and SB-20M agar media.
AB  - OBJECTIVE: The recovery of mutans streptococci in saliva and dental biofilm
      samples depends, in part, on the culture medium used. In this study, we compared
      (i) the culture media Sucrose-Bacitracin agar (SB-20), Modified SB-20 (SB-20M)
      and Mitis Salivarius Bacitracin agar (MSB) in the count of colony forming units
      (cfu) of mutans streptococci and (ii) in the morphological and biochemical
      differentiation between Streptococcus mutans and Streptococcus sobrinus. DESIGN:
      Samples of non-stimulated saliva from 20 children were plated on SB-20, SB-20M
      and MSB, and incubated in microaerophilia at 37 degrees C for 72h. Identification
      of microorganisms was based on analysis of colony morphology under
      stereomicroscopy. The biochemical identification of colonies was done by
      biochemical tests using sugar fermentation, resistance to bacitracin and hydrogen
      peroxide production. RESULTS: There was no significant difference (p>0.05) in the
      number of cfu of mutans streptococci recovered on SB-20 and SB-20M agar.
      Comparing the media, SB-20 and SB-20M yielded a larger number of mutans
      streptococci colonies (p<0.05) and were more effective than MSB in the
      identification of S. sobrinus (p<0.05), but not of S. mutans (p>0.05).
      CONCLUSION: There was no significant difference between SB-20 and SB-20M culture
      media in the count of mutans streptococci, demonstrating that the replacement of
      sucrose by coarse granular cane sugar did not alter the efficacy of the medium.
      Compared with MSB, SB-20 and SB-20M allowed counting a larger number of mutans
      streptococci colonies and a more effective morphological identification of S.
      sobrinus.

PMID- 23149155
TI  - Anti-viral triple therapy with telaprevir in haemodialysed HCV patients: is it
      feasible?
AB  - INTRODUCTION: Chronic hepatitis C virus (HCV) infection is the most common
      chronic liver disease in patients with end stage renal disease (ESRD) and is well
      known as a frequent cause of mortality and graft loss among haemodialysed and
      kidney transplant patients. Up to now, there are no data on antiviral efficacy
      and tolerability of available protease inhibitors (telaprevir and boceprevir) in
      HCV infected haemodialysed patients. METHODS: We report 4 cases of HCV infected
      haemodialysed patients, who have not responded to a prior course of pegylated
      interferon (Peg-IFN) and ribavirin (RBV) and who were listed for kidney
      transplantation (KTx). These 4 patients received a second-line antiviral
      treatment with Peg-IFN, RBV and telaprevir. RESULTS: After 12 weeks of triple
      therapy, tolerability was acceptable and HCV-RNA became undetectable in 3/4
      patients. Mild side-effects included anaemia leading to increasing the doses of
      erythropoietin (EPO). Dose of RBV ranged from 200mg three times a week to
      200mg/day. CONCLUSION: Triple therapy with a first generation protease inhibitor
      could be the new standard for the treatment of HCV patients with ESRD. This needs
      to be confirmed by larger series.

PMID- 23149154
TI  - The segmentation clock: inherited trait or universal design principle?
AB  - Metamerism is a widespread feature of multicellular body plans; however, our
      understanding of the underlying mechanisms that generate these patterns is
      currently based on only a few model organisms. In particular, vertebrate embryos
      use a segmentation clock to rhythmically and sequentially add segments in concert
      with posterior elongation of their body. Recent evidence of a segmentation clock
      acting in arthropods indicates that this mechanism may be a widely used strategy
      for generating serial anatomy in animals. Whether this is due to homology or
      convergence is not yet known, but the recent discovery of an oscillatory process
      associated with the production of sequential root primordia in plants suggests
      that a segmentation clock is a fundamental patterning principle in growing
      tissues, independent of ancestry. In this review, we consider the principles of
      the segmentation clock that may be conserved across the animal and plant
      kingdoms, and discuss opportunities for cross-fertilization between these active
      fields of research.

PMID- 23149156
TI  - Subsoil heterogeneities controlling porewater contaminant mass and microbial
      diversity at a site with a complex pollution history.
AB  - This study seeks to improve our understanding of the conceptual model of
      pollutant transport and fate in cases of DNAPL contamination at sites with a
      complex contamination history. The study was carried out in an unconfined aquifer
      of alluvial fans in the Tarragona Petrochemical Complex (Spain). Two boreholes
      were drilled and continuous cores were recovered in order to carry out a detailed
      core description at centimeter scale and a comprehensive sampling of borehole
      cores. The biogeochemical heterogeneity at these sites is controlled by the
      conjunction of lithological, hydrochemical and microbiological heterogeneities.
      Biodegradation processes of contaminant compounds take place not only at the
      level of the dissolved fraction in the aquifer but also at the level of the
      fraction retained in the fine, less conductive materials as shown by the
      biodegradation haloes of parent and metabolite compounds. Sampling the low
      conductivity levels also allowed us to identify compounds, e.g. BTEX, that are
      the remaining traces of the passage of old contaminant plumes whose sources no
      longer exist. This enabled us to describe past biogeochemical processes and to
      partially account for the processes occurring today. Transition zones,
      characterized by numerous textural changes, constitute ecotones whose
      biostimulation could be effective in promoting the acceleration of the
      remediation of the multiple pollution at these sites.

PMID- 23149157
TI  - Introductory remarks. Molecular, biological and clinical aspects of Alzheimer's
      disease.

PMID- 23149158
TI  - Effects of ranolazine on vasomotor responses of rat aortic rings.
AB  - BACKGROUND AND AIMS: Ranolazine is a piperazine derivative that was approved in
      2006 for the treatment of chronic stable angina. Compared with first-line drugs
      currently used to treat angina, beneficial effects of ranolazine occur without
      changing hemodynamic parameters such as heart rate and blood pressure. In the
      present study the effects of ranolazine on vasomotor responses of rat aortic
      rings were examined. METHODS: Pharmacological evaluation was performed by
      analyzing the vasomotor responses of ranolazine on aortic rings of adult male
      Wistar rats precontracted with phenylephrine (10(-5) M). In each experiment we
      used a pair of rings (with and without endothelium) from the same aorta and
      superfused in the same bath. RESULTS: Ranolazine (10(-6)-10(-4) M) induced a
      concentration-dependent relaxation of phenylephrine-precontracted rings. The
      relaxation was only partially dependent on the presence of the endothelium (56.78
      +/- 6.81% in rings with endothelium and 47.88 +/- 4.70% in rings without
      endothelium). In rings with endothelium, L-NAME induced a shift to the right of
      the concentration-response curve to ranolazine. Blocking the cyclooxygenase
      pathway induced a leftward shift of the concentration relaxation curve to
      ranolazine in both types of rings and increased the ranolazine-induced relaxation
      in rings without endothelium. CONCLUSIONS: Ranolazine has a vasodilatory effect
      that is predominantly endothelium-independent. The synthesis/release of nitric
      oxide by the endothelium may, however, contribute to its relaxing action. These
      effects of ranolazine may contribute to its beneficial effects in patients with
      stable angina.

PMID- 23149159
TI  - Procurement of shared data instruments for Research Electronic Data Capture
      (REDCap).
AB  - REDCap (Research Electronic Data Capture) is a web-based software solution and
      tool set that allows biomedical researchers to create secure online forms for
      data capture, management and analysis with minimal effort and training. The
      Shared Data Instrument Library (SDIL) is a relatively new component of REDCap
      that allows sharing of commonly used data collection instruments for immediate
      study use by research teams. Objectives of the SDIL project include: (1)
      facilitating reuse of data dictionaries and reducing duplication of effort; (2)
      promoting the use of validated data collection instruments, data standards and
      best practices; and (3) promoting research collaboration and data sharing.
      Instruments submitted to the library are reviewed by a library oversight
      committee, with rotating membership from multiple institutions, which ensures
      quality, relevance and legality of shared instruments. The design allows
      researchers to download the instruments in a consumable electronic format in the
      REDCap environment. At the time of this writing, the SDIL contains over 128 data
      collection instruments. Over 2500 instances of instruments have been downloaded
      by researchers at multiple institutions. In this paper we describe the library
      platform, provide detail about experience gained during the first 25months of
      sharing public domain instruments and provide evidence of impact for the SDIL
      across the REDCap consortium research community. We postulate that the shared
      library of instruments reduces the burden of adhering to sound data collection
      principles while promoting best practices.

PMID- 23149160
TI  - Knowledge-based personalized search engine for the Web-based Human
      Musculoskeletal System Resources (HMSR) in biomechanics.
AB  - Human musculoskeletal system resources of the human body are valuable for the
      learning and medical purposes. Internet-based information from conventional
      search engines such as Google or Yahoo cannot response to the need of useful,
      accurate, reliable and good-quality human musculoskeletal resources related to
      medical processes, pathological knowledge and practical expertise. In this
      present work, an advanced knowledge-based personalized search engine was
      developed. Our search engine was based on a client-server multi-layer multi-agent
      architecture and the principle of semantic web services to acquire dynamically
      accurate and reliable HMSR information by a semantic processing and visualization
      approach. A security-enhanced mechanism was applied to protect the medical
      information. A multi-agent crawler was implemented to develop a content-based
      database of HMSR information. A new semantic-based PageRank score with related
      mathematical formulas were also defined and implemented. As the results, semantic
      web service descriptions were presented in OWL, WSDL and OWL-S formats.
      Operational scenarios with related web-based interfaces for personal computers
      and mobile devices were presented and analyzed. Functional comparison between our
      knowledge-based search engine, a conventional search engine and a semantic search
      engine showed the originality and the robustness of our knowledge-based
      personalized search engine. In fact, our knowledge-based personalized search
      engine allows different users such as orthopedic patient and experts or
      healthcare system managers or medical students to access remotely into useful,
      accurate, reliable and good-quality HMSR information for their learning and
      medical purposes.

PMID- 23149161
TI  - Phase angle from BIA as a prognostic and nutritional status tool for children and
      adolescents undergoing hematopoietic stem cell transplantation.
AB  - BACKGROUND & AIMS: The phase angle (PA) has been considered a prognostic and
      nutritional status indicator in several clinical situations considering its use
      as a body cell mass estimate value. The aim of this study was to evaluate the
      association between PA and other methods of nutritional assessment, as well as
      its prognostic value for children and adolescents undergoing hematopoietic stem
      cell transplantation (HSCT). METHODS: The nutritional status of 67 patients and
      35 controls was assessed by bioelectric impedance analysis and anthropometric
      measurements. The phase angle was calculated and expressed in degrees and
      standardized (SPA) according to reference values. The Kaplan-Meier method was
      used to calculate survival and Kappa coefficient to determine the concordance
      between the SPA and other parameters of nutritional assessment. The correlation
      was established by using Pearson's correlation analysis. RESULTS: SPA
      progressively decreased during the treatment. The agreement between SPA and the
      diagnosis of malnutrition was moderate to %ideal weight, %TSF and %AMC and weak
      for BMI and weight/age z-score. Patients who had severe weight loss after
      transplantation had lower levels of SPA as compared to the group that did not
      lose weight (p < 0.001). Patients who developed chronic graft-versus-host disease
      had lower levels of SPA (p = 0.02), as well as patients who had been using
      corticosteroids during the post-transplant phase (p = 0.03). In this case, there
      was an inverse correlation between drug dose and SPA (p = 0.01). Patients with
      SPA <= 0 SD had a lower survival time as compared to the group of patients with
      SPA > 0 SD (p = 0.02) and showed an increased risk of death of 5.1as compared to
      the other group (95% CI: 1.41-18.94). CONCLUSION: The present study suggests that
      SPA could be useful as an indicator of survival and nutritional status for
      patients undergoing HSCT.

PMID- 23149162
TI  - New endoscopic classification for subscapularis lesions.
AB  - BACKGROUND: The absence of a coherent classification system has hampered
      communication about the treatment and outcomes of the various types of
      subscapularis tendon lesions. In addition, a reliable classification system
      allows comparisons of epidemiological and therapeutic data. The classification
      systems used until now fail to incorporate the radiological and intraoperative
      abnormalities of the bicipital sling, and they do not consider the degree of
      subscapularis tendon cleavage. Here, we describe a new arthroscopy-based
      classification system intended for therapeutic and prognostic purposes. METHODS:
      A prospective multicentre study sponsored by the French Society for Arthroscopy
      was conducted from March 2010 to January 2011 in 150 isolated subscapularis
      lesions with or without limited anterosuperior involvement. The bicipital sling
      and insertion of the deep subscapularis layer were routinely investigated by
      arthroscopy with video recording. Each lesion was classified after a consensus
      was reached among four surgeons. RESULTS: We identified four lesion types based
      on the bicipital sling findings. Type I was defined as partial separation of the
      subscapularis tendon fibres from the lesser tuberosity with a normal bicipital
      sling. Type II consisted of a partial subscapularis tear at the lesser tuberosity
      attachment combined with partial injury to the anterior wall of the bicipital
      sling, without injury to the superior glenohumeral ligament. Type III was
      complete separation of the subscapularis fibres from the lesser tuberosity with
      extensive cleavage of the bicipital sling. Finally, in Type IV, all the
      subscapularis fibres were detached and, in some cases, conjunction of the
      subscapularis and supraspinatus fibres produced the comma sign. Nearly all the
      lesions identified intraoperatively during the study fit one of these four types.
      DISCUSSION: A reproducible classification system that allows different surgeons
      to establish comparable homogeneous patient groups is useful for both therapeutic
      and prognostic purposes. We defined four types of subscapularis lesions that are
      easy to identify as either isolated lesions or combined with anterosuperior
      rotator cuff tears. Long head of biceps tendon abnormalities and fatty
      degeneration of the shoulder muscles can be added to our classification system.
      Studies of intraobserver and interobserver reproducibility are needed to complete
      the process of validating the diagnostic and/or prognostic usefulness of this new
      classification scheme.

PMID- 23149163
TI  - A health survey of Beijing middle-aged registered nurses during menopause.
AB  - OBJECTIVE: To collect health information of Beijing middle-aged registered nurses
      during menopause. METHODS: We distributed self-administered questionnaires to
      2100 registered nurses aged 40-55 from 20 hospitals in Beijing. The objects of
      interest were selected by cluster sampling. RESULTS: A total of 1686
      questionnaires met the criteria and were used for statistical analysis. The
      average natural menopause age was 48.68 +/- 3.61 years old. We determined that
      37.83% of the objects had modified Kupperman Menopausal Index (KMI) scores >= 15.
      The top three menopause symptoms were fatigue (82.72%), irritability (70.24%),
      and arthralgia/myalgia (69.55%); hot flashes ranked eleventh (30.83%).
      CONCLUSIONS: A total of 37.83% Beijing middle-aged registered nurses had
      menopause syndrome, and the top three symptoms were fatigue, irritability, and
      arthralgia/myalgia.

PMID- 23149164
TI  - Associations between a priori-defined dietary patterns and longitudinal changes
      in bone mineral density in adolescents.
AB  - OBJECTIVE: To quantify short- and long-term associations between dietary patterns
      defined a priori and bone mineral density (BMD) during adolescence. DESIGN:
      Dietary patterns were defined at 13 years old using a Mediterranean diet (MD)
      quality index, the Dietary Approaches to Stop Hypertension (DASH) diet index and
      the Oslo Health Study (OHS) dietary index. Linear regression coefficients were
      used to estimate associations between dietary patterns and forearm BMD at 13 and
      17 years, measured by dual-energy X-ray absorptiometry. SETTING: Public and
      private schools of Porto, Portugal. SUBJECTS: The EPITeen cohort comprising 1180
      adolescents born in 1990, recruited at schools during the 2003/2004 school year
      and re-evaluated in 2007/2008. RESULTS: In girls, at 13 years, mean BMD (g/cm2)
      in the first and third tertiles was 0.369 and 0.368 for the MD pattern, 0.368 and
      0.369 for the DASH diet, and 0.370 and 0.363 for the OHS index. In boys, mean BMD
      (g/cm2) in the first and third tertiles was 0.338 and 0.347 for the MD pattern,
      0.342 and 0.346 for the DASH diet, and 0.344 and 0.342 for the OHS index. None of
      these differences were significant. Mean BMD at 17 years and prospective
      variation were also not significantly different between tertiles of adherence to
      each score. However, a trend of increased BMD at 13 years with greater adherence
      to the MD pattern was observed in boys (adjusted coefficient = 0.248; 95% CI
      0.052, 0.444). CONCLUSIONS: The selected dietary patterns may not capture truly
      important dietary differences in determining BMD or diet may not be, beyond
      nutrient adequacy, a limiting determinant of BMD.

PMID- 23149165
TI  - Radiation and the risk of chronic lymphocytic and other leukemias among chornobyl
      cleanup workers.
AB  - BACKGROUND: Risks of most types of leukemia from exposure to acute high doses of
      ionizing radiation are well known, but risks associated with protracted
      exposures, as well as associations between radiation and chronic lymphocytic
      leukemia (CLL), are not clear. OBJECTIVES: We estimated relative risks of CLL and
      non-CLL from protracted exposures to low-dose ionizing radiation. METHODS: A
      nested case-control study was conducted in a cohort of 110,645 Ukrainian cleanup
      workers of the 1986 Chornobyl nuclear power plant accident. Cases of incident
      leukemia diagnosed in 1986-2006 were confirmed by a panel of expert
      hematologists/hematopathologists. Controls were matched to cases on place of
      residence and year of birth. We estimated individual bone marrow radiation doses
      by the Realistic Analytical Dose Reconstruction with Uncertainty Estimation
      (RADRUE) method. We then used a conditional logistic regression model to estimate
      excess relative risk of leukemia per gray (ERR/Gy) of radiation dose. RESULTS: We
      found a significant linear dose response for all leukemia [137 cases, ERR/Gy =
      1.26 (95% CI: 0.03, 3.58]. There were nonsignificant positive dose responses for
      both CLL and non-CLL (ERR/Gy = 0.76 and 1.87, respectively). In our primary
      analysis excluding 20 cases with direct in-person interviews < 2 years from start
      of chemotherapy with an anomalous finding of ERR/Gy = -0.47 (95% CI: < -0.47,
      1.02), the ERR/Gy for the remaining 117 cases was 2.38 (95% CI: 0.49, 5.87). For
      CLL, the ERR/Gy was 2.58 (95% CI: 0.02, 8.43), and for non-CLL, ERR/Gy was 2.21
      (95% CI: 0.05, 7.61). Altogether, 16% of leukemia cases (18% of CLL, 15% of non
      CLL) were attributed to radiation exposure. CONCLUSIONS: Exposure to low doses
      and to low dose-rates of radiation from post-Chornobyl cleanup work was
      associated with a significant increase in risk of leukemia, which was
      statistically consistent with estimates for the Japanese atomic bomb survivors.
      Based on the primary analysis, we conclude that CLL and non-CLL are both
      radiosensitive.

PMID- 23149166
TI  - Identification, sequence analysis and characterization of Clonorchis sinensis
      ubiquitin.
AB  - Ubiquitin is a functionally important protein expressed in eukaryotic cells
      usually encoded by multigenic families containing two types of genes, ubiquitin
      extension genes and polyubiquitin genes. One independent monomeric locus and two
      independent polyubiquitin loci were firstly identified from the genome of
      carcinogenic liver fluke, Clonorchis sinensis (C. sinensis). The nucleotide and
      amino acid sequence of C. sinensis polyubiquitin, especially polyubiquitin with
      five tandem ubiquitin repeats (CsPUB5), were analyzed. We obtained recombinant
      CsPUB5 (rCsPUB5) and anti-rCsPUB5 IgG. The ubiquitin transcripts in life cycle of
      C. sinensis were investigated. In addition, we found that ubiquitin or
      ubiquitination was ubiquitous in adult worm of C. sinensis and significantly
      observed in the content of biliary tract and intrahepatic biliary epithelium of
      liver from C. sinensis infected rat. We confirmed that rCsPUB5 could bind to
      human intrahepatic biliary epithelial cell by immunofluorescence in vitro. It was
      considered that ubiquitin family constitutively expressed in C. sinensis for
      variety of cellular processes and might be implicated in the genesis and
      progression of cholangiocarcinoma induced by the infection of C. sinensis.

PMID- 23149167
TI  - The role of non-synaptic extracellular glutamate.
AB  - Although there are some mechanisms which allow the direct crossing of substances
      between the cytoplasm of adjacent cells (gap junctions), most substances use the
      extracellular space to diffuse between brain cells. The present work reviews the
      behavior and functions of extracellular glutamate (GLU). There are two
      extracellular pools of glutamate (GLU) in the brain, a synaptic pool whose
      functions in the excitatory neurotransmission has been widely studied and an
      extrasynaptic GLU pool although less known nonetheless is gaining attention among
      a growing number of researchers. Evidence accumulated over the last years shows a
      number of mechanisms capable of releasing glial GLU to the extracellular medium,
      thus modulating neurons, microglia and oligodendrocytes, and regulating the
      immune response, cerebral blood flow, neuronal synchronization and other brain
      functions. This new scenario is expanding present knowledge regarding the role of
      GLU in the brain under different physiological and pathological conditions. This
      article is part of a Special Issue entitled 'Extrasynaptic ionotropic receptors'.

PMID- 23149168
TI  - betaCCT, an antagonist selective for alpha(1)GABA(A) receptors, reverses diazepam
      withdrawal-induced anxiety in rats.
AB  - The abrupt discontinuation of prolonged benzodiazepine treatment elicits a
      withdrawal syndrome with increased anxiety as a major symptom. The neural
      mechanisms underlying benzodiazepine physical dependence are still insufficiently
      understood. Flumazenil, the non-selective antagonist of the benzodiazepine
      binding site of GABA(A) receptors was capable of preventing and reversing the
      increased anxiety during benzodiazepine withdrawal in animals and humans in some,
      but not all studies. On the other hand, a number of data suggest that GABA(A)
      receptors containing alpha(1) subunits are critically involved in processes
      developing during prolonged use of benzodiazepines, such are tolerance to
      sedative effects, liability to physical dependence and addiction. Hence, we
      investigated in the elevated plus maze the level of anxiety 24 h following 21
      days of diazepam treatment and the influence of flumazenil or a preferential
      alpha(1)-subunit selective antagonist betaCCt on diazepam withdrawal syndrome in
      rats. Abrupt cessation of protracted once-daily intraperitoneal administration of
      2 mg/kg diazepam induced a withdrawal syndrome, measured by increased anxiety
      like behavior in the elevated plus maze 24 h after treatment cessation. Acute
      challenge with either flumazenil (10mg/kg) or betaCCt (1.25, 5 and 20 mg/kg)
      alleviated the diazepam withdrawal-induced anxiety. Moreover, both antagonists
      induced an anxiolytic-like response close, though not identical, to that seen
      with acute administration of diazepam. These findings imply that the mechanism by
      which antagonism at GABA(A) receptors may reverse the withdrawal-induced anxiety
      involves the alpha(1) subunit and prompt further studies aimed at linking the
      changes in behavior with possible adaptive changes in subunit expression and
      function of GABA(A) receptors.

PMID- 23149169
TI  - Cigarette smoking, psychopathology and cognitive function in first-episode drug
      naive patients with schizophrenia: a case-control study.
AB  - BACKGROUND: Although patients with chronic schizophrenia have substantially
      higher smoking rates than either the general population or patients with other
      mental illnesses, drug-naive patients with a first episode of schizophrenia have
      received little systemic study. This study examined smoking rates, the
      association between smoking and symptom severity and cognitive function in
      Chinese first-episode schizophrenia (FES) patients using cross-sectional and case
      control designs. METHOD: Two hundred and forty-four drug-naive FES patients and
      256 healthy controls matched for gender, age and education completed the
      Fagerstrom Test for Nicotine Dependence (FTND) and the Repeatable Battery for the
      Assessment of Neuropsychological Status (RBANS). Patients were also rated on the
      Positive and Negative Symptom Scale (PANSS). RESULTS: The rate and quantity of
      smoking were not significantly higher among FES patients compared to the general
      population. Among patients, smokers scored higher than non-smokers on the total
      PANSS and the positive symptom subscale scores. There were no significant
      associations between cognitive function and smoking in either FES patients or
      healthy controls. CONCLUSIONS: In contrast to studies in patients with chronic
      schizophrenia, drug-naive FES patients did not smoke more frequently than the
      general population. Furthermore, patients with psychotic disorders who smoked did
      not exhibit significant cognitive differences compared with those who did not
      smoke. However, smoking may have other detrimental effects on physical and mental
      health, for example on positive symptoms.

PMID- 23149170
TI  - A diagnostic dilemma: inflammatory linear verrucous epidermal nevus versus linear
      psoriasis.

PMID- 23149171
TI  - Vitamin D status in neonates undergoing cardiac operations: relationship to
      cardiopulmonary bypass and association with outcomes.
AB  - OBJECTIVES: To determine the incidence of vitamin D deficiency in neonates with
      congenital heart disease and whether differences exist by race. In addition, we
      determined the effect of cardiopulmonary bypass on vitamin D levels and explored
      associations between 25-hydroxyvitamin D [25(OH)D] levels and postoperative
      outcomes. STUDY DESIGN: We performed a secondary analysis of a prospective
      randomized controlled trial in 70 neonates undergoing cardiac surgery. The
      neonates' 25(OH)D levels were measured in the operating room before skin incision
      (baseline), at the cessation of cardiopulmonary bypass, and at 24 hours
      postoperatively. Associations between these levels and clinical outcomes were
      explored. Vitamin D deficiency was defined as a 25(OH)D level <20 ng/mL. RESULTS:
      Vitamin D deficiency was present in 84% (59/70); concentrations in African
      Americans (n = 20) were significantly lower than those of Caucasian/other
      race/ethnicity (n = 50) (10.2 +/- 4.2 vs 16.0 +/- 5.6 ng/mL, P < .0001). The 24
      hour postoperative 25(OH)D levels were not different from baseline and correlated
      with a reduced postoperative inotropic requirement (r = -0.316, P = .008).
      CONCLUSIONS: Vitamin D deficiency is prevalent in neonates with congenital
      cardiac defects, and lower postoperative 25(OH)D levels are associated with the
      need for increased inotropic support in neonates undergoing cardiac operations.
      These findings support that vitamin D deficiency may play a role in myocardial
      injury and postoperative recovery and warrants further investigation.

PMID- 23149172
TI  - Acute kidney injury in asphyxiated newborns treated with therapeutic hypothermia.
AB  - OBJECTIVE: To test the hypothesis that acute kidney injury (AKI) would be
      independently associated with increased morbidity and mortality. STUDY DESIGN: A
      total of 96 consecutively cooled infants were reviewed retrospectively. Modified
      Acute Kidney Injury Network criteria were used to classify AKI based on absolute
      rise in serum creatinine (SCr) level from a previous trough (stage I, rise in SCr
      of 0.3 mg/dL or SCr 150-<200%; stage II, rise in SCr of 200-<300%; stage III,
      rise in SCr of >=300%, SCr 2.5 mg/dL, or dialysis). Outcomes were mortality,
      duration of neonatal intensive care unit (NICU) stay, and duration of mechanical
      ventilation. RESULTS: AKI occurred in 36 of 96 infants (38%). Overall mortality
      was 7% and was higher for those with AKI, with the difference approaching
      statistical significance (14% vs 3% in those without AKI; P = .099). Patients
      with AKI stayed longer in the NICU (mean, 15.4 +/- 9.3 days vs 11 +/- 5.9 days; P
      = .014) and required prolonged mechanical ventilation (mean, 9.7 +/- 5.9 days vs
      4.8 +/- 3.7 days; P < .001). On multivariate analysis, AKI remained predictive of
      prolonged duration of mechanical ventilation and prolonged NICU stay. CONCLUSION:
      We used the Acute Kidney Injury Network definition for AKI in asphyxiated
      newborns undergoing therapeutic hypothermia to demonstrate that the incidence of
      AKI remains high, but lower than rates published before the advent of therapeutic
      hypothermia. We highlight the importance of recognizing AKI in asphyxiated
      newborns undergoing therapeutic hypothermia, along with the potential benefits of
      early recognition.

PMID- 23149174
TI  - Marching towards personalized genomic medicine.

PMID- 23149173
TI  - Impact of gestational diabetes mellitus on pubertal changes in adiposity and
      metabolic profiles in Latino offspring.
AB  - OBJECTIVE: To examine the impact of maternal gestational diabetes mellitus (GDM)
      status on longitudinal changes in adiposity and metabolic variables in overweight
      Latino offspring (from age 8-20 years) across puberty. STUDY DESIGN: This
      longitudinal cohort of 210 overweight Latino children was measured annually for a
      period of 3 +/- 1 years for Tanner stage through physical examination, adiposity
      by dual-energy X-ray absorptiometry and magnetic resonance imaging, lipids, and
      glucose and insulin action via the oral glucose tolerance test and frequently
      sampled intravenous glucose tolerance test. Linear mixed-effects modeling
      estimated the impact of maternal GDM status on baseline and changes in adiposity
      and metabolic variables across puberty. RESULTS: In our cohort, 22% of offspring
      were from GDM pregnancies. At baseline, the GDM offspring were heavier at birth,
      more likely to have a family history of type 2 diabetes, and less likely to have
      been breastfed (for any duration). Compared with the non-GDM offspring, the GDM
      offspring had greater increases in total body fat (+6.5% vs +4.5%; P = .03) and
      steeper declines in acute insulin response (-39% vs -17%; P < .001) and
      disposition index (-57% vs -35%; P < .001) across Tanner stages, independent of
      ethnicity, sex, breastfeeding status, family history of diabetes, and baseline
      and changes in body composition. CONCLUSION: These findings confirm the elevated
      risk for excess adiposity and type 2 diabetes in GDM offspring, and further
      underscore the need for interventions targeting Latino GDM and their offspring.

PMID- 23149175
TI  - Alexander disease.

PMID- 23149176
TI  - Alarming signs in the Manchester triage system: a tool to identify febrile
      children at risk of hospitalization.
AB  - OBJECTIVES: To assess whether the flowcharts and discriminators of the Manchester
      Triage System (MTS) can be used as indicators of alarming signs of serious
      febrile illness to predict the risk of hospitalization for febrile children who
      present at the emergency department (ED). STUDY DESIGN: Observational study,
      which included 2455 children (<16 years) who came to the ED of a university
      hospital with fever as their main complaint (May 2007-July 2009). Alarming signs
      for serious febrile illness were matched with MTS flowcharts and discriminators.
      At triage, the percentage of alarming signs positive was calculated. The
      diagnostic ability of the percentage of alarming signs positive to identify
      children at risk of hospitalization was assessed by calculating positive and
      negative likelihood ratios. RESULTS: Thirty percent of children had at least 1
      alarming sign positive at triage. Twenty-three percent were hospitalized.
      Positive likelihood ratios of hospitalization were 5.0 (95% CI: 3.9-6.5) for
      children with >20% of alarming signs positive at triage and 12.0 (95% CI: 5.2
      27.6) for those with >40% of alarming signs positive. Negative likelihood ratios
      were 0.8 (95% CI: 0.8-0.8) and 1.0 (95% CI: 0.9-1.0), respectively. CONCLUSIONS:
      By alternatively using the flowcharts and discriminators of the MTS as alarming
      signs, rather than urgency classifiers, the MTS can function as a simple, readily
      available tool to identify febrile children at risk of hospitalization early in
      the care process. This knowledge may help to improve ED throughput times as well
      as admission and discharge management at pediatric EDs.

PMID- 23149177
TI  - Klein line on the anteroposterior radiograph is not a sensitive diagnostic
      radiologic test for slipped capital femoral epiphysis.
AB  - OBJECTIVE: To correlate the amount of slipped capital femoral epiphysis (SCFE)
      that results in an abnormality of the Klein line. In mild slips, the Klein line
      on the anteroposterior (AP) radiograph may remain normal, potentially leading to
      a delay in diagnosis and emphasizing the importance of obtaining a frog lateral
      radiograph in patients with a suspected SCFE. STUDY DESIGN: A retrospective
      review of 55 patients with SCFE was performed from January 2004-March 2009. Of
      the 55 patients, 32 were missing radiographs and were excluded, leaving 23. The
      23 sets of radiographs were reviewed. RESULTS: Of the 23 hips studied with SCFE,
      only 9 (39%) were able to be diagnosed on the AP radiograph using the classic
      definition of the Klein line. Twenty cases (87%) of SCFE were identified on the
      AP radiograph using the modified Klein line. All 23 cases (100%) of SCFE were
      identified on frog lateral radiographs. CONCLUSIONS: Relying on the Klein line
      will fail to identify many mild or moderate slips. An AP and a frog lateral
      pelvic radiograph should be obtained in any child when an SCFE is suspected to
      accurately identify the disorder and to prevent delays in diagnosis.

PMID- 23149178
TI  - 0.5 mg/kg versus 1 mg/kg of intravenous omeprazole for the prophylaxis of
      gastrointestinal bleeding in critically ill children: a randomized study.
AB  - OBJECTIVE: To compare the effect of 2 doses of intravenous omeprazole on gastric
      pH, gastrointestinal bleeding, and adverse effects in critically ill children.
      STUDY DESIGN: We undertook a prospective randomized clinical trial in critically
      ill children at risk of gastrointestinal bleeding. The effect of 2 intravenous
      omeprazole regimens (0.5 or 1 mg/kg every 12 hours) on the gastric pH and
      incidence of gastrointestinal hemorrhage was compared. The efficacy criteria were
      a gastric pH >4 and the absence of clinically significant gastrointestinal
      bleeding. RESULTS: Forty patients, 20 in each treatment group, were studied.
      Overall, the gastric pH was greater than 4 for 57.8% of the time, with no
      difference between the doses (P = .66). The percentage of time with a gastric pH
      > 4 increased during the study (47.8% between 0 and 24 hours vs 76% between 24
      and 48 hours, P = .001); the greater dose showed a greater increase in the
      percentage of time with a pH > 4: between hours 24 and 48 of the study, the
      gastric pH was greater than 4 for 84.5% of the time with the 1 mg/kg dose and for
      65.5% of the time with the 0.5 mg/kg dose (P = .036). Plasma omeprazole levels
      were greater with 1 mg/kg dose, but no correlation was found between omeprazole
      plasma levels and gastric pH. No toxic adverse effects were detected, and there
      was no clinically significant bleeding. CONCLUSION: Neither of the 2 omeprazole
      regimens achieved adequate alkalinization of the gastric pH during the first 24
      hours. Between 24 and 48 hours, the 1 mg/kg dose maintained the gastric pH
      greater than 4 for a greater percentage of the time.

PMID- 23149179
TI  - Aspirin sensitivity syndrome (Samter's Triad): an unrecognized disorder in
      children with nasal polyposis.
AB  - Aspirin sensitivity syndrome is an underdiagnosed entity in pediatric
      otolaryngology. The diagnosis must be considered in a pediatric non-cystic
      fibrosis patient with florid nasal polyposis. In this small case series, we will
      describe 2 patient's presentation, work up, allergic and surgical therapies and
      their postoperative course. In doing so, we hope to increase awareness and to
      illustrate the details that are involved in its diagnosis and treatment.

PMID- 23149180
TI  - Stevens-Johnson syndrome: an oral viewpoint.
AB  - The Stevens-Johnson syndrome (SJS) is a severe variant of erythema multiforme
      (EM) that occasionally can rise to systemic upset and possibly compromise life.
      In this report, we described important oral and dermatologic aspects of a case of
      SJS triggered by Mycoplasma pneumoniae infection.

PMID- 23149181
TI  - Significance of autochthonous Bacillus sp. KK1 on biomineralization of lead in
      mine tailings.
AB  - The aim of the study was to isolate and characterize potential autochthonous
      bacteria for biomineralization of Pb in mine tailings. A total of four bacteria
      were isolated from the soil samples and assayed for tolerance to Pb and other
      heavy metals. Isolate KK1 exhibited maximum Pb resistance and was subsequently
      identified as Bacillus sp. based on the partial 16S rRNA gene sequences. The
      isolate KK1 reduced the Pb ions and did not harbor pbrT gene. Selective
      sequential extraction of bioaugmented soil revealed that the isolate
      significantly reduced (26%) the exchangeable fraction and increased (38%) the
      carbonate fraction of Pb. X-ray diffraction studies confirmed the role of
      bacterially induced calcite precipitation in the bioremediation of mine tailings.
      A significant increase in the urease (334%), DHO (dehydrogenase) (14%), and
      phosphatase (37%) activity was observed in the bioaugmented mine soil.

PMID- 23149182
TI  - Partitioning and bioaccumulation of metals from oil sands process affected water
      in indigenous Parachlorella kessleri.
AB  - This paper studies the partitioning and bioaccumulation of ten target metals
      ((53)Cr, Mn, Co, (60)Ni, (65)Cu, (66)Zn, As, (88)Sr, (95)Mo and Ba) from oil
      sands tailings pond water (TPW) by indigenous Parachlorella kessleri. To
      determine the role of extracellular and intracellular bioaccumulation in metal
      removal by P. kessleri, TPW samples taken from two oil sands operators (Syncrude
      Canada Ltd. and Albian Sands Energy Inc.) were enriched with nutrient
      supplements. Results indicate that intracellular bioaccumulation played the main
      role in metal removal from TPW; whereas extracellular bioaccumulation was only
      observed to some extent for Mn, Co, (60)Ni, (65)Cu, (88)Sr, (95)Mo and Ba. The
      FTIR scan and titration of functional groups on the cell surface indicated low
      metal binding capacity by indigenous P. kessleri. However, it is believed that
      the dissolved cations and organic ligand content in TPW (such as naphthenic
      acids) may interfere with metal binding on the cell surface and lower
      extracellular bioaccumulation. In addition, the total bioaccumulation and
      bioconcentration factor (BCF) varied during the cultivation period in different
      growth regimes.

PMID- 23149183
TI  - High prevalence of infections and pathological changes in burbot (Lota lota) from
      a polluted lake (Lake Mjosa, Norway).
AB  - The aim of the present study was to investigate whether exposure to high levels
      of persistent organic pollutants (POPs) affected a fish population in Lake Mjosa.
      Lake Mjosa is known to be contaminated by polybrominated diphenyl ethers (PBDEs),
      a subgroup of brominated flame retardants from local industrial activities. Fish
      from Lake Losna, a less contaminated lake located close to Lake Mjosa, was used
      as reference (control). The sampling of burbot (Lota lota) was carried out
      between 2005 and 2008. Hepatic levels of POPs were analysed in burbot from the
      two lakes, and the fish were examined for bacterial- and parasite infection and
      histopathological changes. The levels of polychlorinated biphenyls (PCBs),
      dichlorodiphenyltrichloroethanes (DDTs), and PBDEs were about 10, 15 and 300
      times higher in fish from Lake Mjosa compared to fish from Lake Losna.
      Mycobacterium salmoniphilum was present in 7% and 35% of the fish from Lake Losna
      and Lake Mjosa respectively. Significantly higher number of external and visceral
      macroscopic lesions, histopathological diffuse changes and granulomas were seen
      in fish from Lake Mjosa compared to Lake Losna. Furthermore the parasite
      infection was higher and the hepatic lipid content was significantly lower in
      burbot from Lake Mjosa. The results of the present study suggest that the high
      level of contamination in Lake Mjosa could have a negative impact on the health
      status of wild fish inhabiting the lake.

PMID- 23149185
TI  - An integrated approach to understanding the sorption mechanism of phenanthrene by
      cork.
AB  - Previous studies have shown the high sorption affinity of polycyclic aromatic
      hydrocarbons by cork. The aim of the present work is to go further by
      investigating the sorption mechanism of polycyclic aromatic hydrocarbons
      (exemplified by phenanthrene) on cork and the availability of the chemical
      components (i.e. lignin, suberin, holocellulose and extractives) to retain
      phenanthrene. Two approaches were integrated to reach this objective: (1)
      statistical multivariate analysis to obtain correlations between the sorption
      capacity, measured as K(oc), and the sorbent properties (i.e. polarity, acidic
      functional groups, %dichloromethane extractives, %ethanol and water extractives,
      %suberin, %lignin and %holocellulose) and (2) modeling calculations to obtain
      information on interaction at the molecular level. The statistical multivariate
      analysis demonstrated a strong and positive correlation between K(oc) and the
      lignin content as well as negative correlations between K(oc) and the phenolic
      groups and %dichloromethane extractives contents. The modeling study showed that
      the lignin-phenanthrene interaction is mostly hydrophobic in nature being largely
      determined by the pi-stacking interaction between the aromatic groups of the
      interacting partners. This result justifies the observed correlations as
      dichloromethane extractives, being hydrophobic, compete with phenanthrene
      adsorption, whereas phenolic groups, as well as negatively charged groups,
      enhance the hydrophilic character of the sorbent surface, thus hindering the
      adsorption of phenanthrene.

PMID- 23149184
TI  - Dietary assessment of human exposure to PBDEs in South Korea.
AB  - This study was conducted to measure the concentration of PBDEs in various food
      stuffs from Korea and to estimate levels of PBDE intake from food for the Korean
      population according to geographical location and age. 20 types of food samples
      were collected from four heavily populated cities (Seoul, Gwangju, Daejeon,
      Pusan) and one rural city (Gangneung) and were analyzed for 19 polybrominated
      diphenyl ether congeners (BDE 15, 17, 28, 33, 47, 49, 66, 71, 85, 99, 100, 119,
      126, 138, 153, 154, 183, and 209). No significant differences in total PBDE
      levels in foods were found among four large cities (Gwangju; 10.91 ng g(-1) wet
      weight (ww), Seoul; 7.66 ng g(-1)ww, Daejeon; 6.91 ng g(-1)ww, Pusan; 6.87 ng g(
      1)ww) and one rural city (Gangneung; 8.72 ng g(-1)ww). Daily dietary intake of
      PBDEs does not appear to be related to the extent of urbanization. Total dietary
      intake of PBDE for the average general population was 72.30 ng d(-1) (not
      detected (ND)=0) which was similar to other countries. In all food groups, the
      largest contribution to PBDE intake was from fish and shellfish (48.96 ng d(-1)).
      Total PBDE consumed per kilogram of body weight was estimated to range from 2.70
      ng kg(-1)d(-1) for infants 1 through 2 years of age to 0.85 ng kg(-1)d for 65
      years and older and was highest in young children and decreased with increasing
      age.

PMID- 23149186
TI  - Soil contamination by brominated flame retardants in open waste dumping sites in
      Asian developing countries.
AB  - In Asian developing countries, large amounts of municipal wastes are dumped into
      open dumping sites each day without adequate management. This practice may cause
      several adverse environmental consequences and increase health risks to local
      communities. These dumping sites are contaminated with many chemicals including
      brominated flame retardants (BFRs) such as polybrominated diphenyl ethers (PBDEs)
      and hexabromocyclododecanes (HBCDs). BFRs may be released into the environment
      through production processes and through the disposal of plastics and electronic
      wastes that contain them. The purpose of this study was to elucidate the status
      of BFR pollution in municipal waste dumping sites in Asian developing countries.
      Soil samples were collected from six open waste dumping sites and five reference
      sites in Cambodia, India, Indonesia, Malaysia, and Vietnam from 1999 to 2007. The
      results suggest that PBDEs are the dominant contaminants in the dumping sites in
      Asian developing countries, whereas HBCD contamination remains low.
      Concentrations of PBDEs and HBCDs ranged from ND to 180 MUg/kg dry wt and ND to
      1.4 MUg/kg dry wt, respectively, in the reference sites and from 0.20 to 430
      MUg/kg dry wt and ND to 2.5 MUg/kg dry wt, respectively, in the dumping sites.
      Contamination levels of PBDEs in Asian municipal dumping sites were comparable
      with those reported from electronic waste dismantling areas in Pearl River delta,
      China.

PMID- 23149187
TI  - Metal mobilization in soil by two structurally defined polyphenols.
AB  - Polyphenols including tannins comprise a large percentage of plant detritus such
      as leaf litter, and affect soil processes including metal dynamics. We tested the
      effects of tannins on soil metal mobilization by determining the binding
      stoichiometries of two model polyphenols to Al(III) and Fe(III) using micelle
      mediated separation and inductively coupled plasma optical emission spectroscopy
      (ICP-OES). By fitting the data to the Langmuir model we found the higher
      molecular weight polyphenol (oenothein B) was able to bind more metal than the
      smaller polyphenol (epigallocatechin gallate, EGCg). For example, oenothein B
      bound 9.43 mol Fe mol(-1), while EGCg bound 4.41 mol of Fe mol(-1). Using the
      parameters from the binding model, we applied the Langmuir model for competitive
      binding to predict binding for mixtures of Al(III) and Fe(III). Using the
      parameters from the single metal experiments and information about polyphenol
      sorption to soils we built a model to predict metal mobilization from soils
      amended with polyphenols. We tested the model with three natural soils and found
      that it predicted mobilization of Fe and Al with r(2)=0.92 and r(2)=0.88,
      respectively. The amount of metal that was mobilized was directly proportional to
      the maximum amount of metal bound to the polyphenol. The secondary parameter in
      each model was the amount of weak organically chelated Fe or Al that was in the
      soil. This study provides the first compound-specific information about how
      natural polyphenols interact with metals in the environment. We propose a model
      that is applicable to developing phytochelation agents for metal detoxification,
      and we discuss how tannins may play a role in metal mobilization from soils.

PMID- 23149188
TI  - Concentration of polychlorinated biphenyls and organochlorine pesticides in
      mullet (Mugil cephalus) and sea bass (Dicentrarchus labrax) from Bizerte Lagoon
      (Northern Tunisia).
AB  - Concentrations of polychlorinated biphenyls (PCBs), and organochlorine pesticides
      (OCPs) were determined in two fish species, mullet (Mugil cephalus) and sea bass
      (Dicentrarchus labrax), collected from Bizerte Lagoon and the Mediterranean Sea.
      In all samples, PCBs were found in higher concentrations than OCPs. The highest
      concentrations of OCPs and PCBs were found in sea bass, and in Bizerte Lagoon.
      Concentrations of DDTs and PCBs detected in this study were generally comparable
      or slightly higher than those found in studies from other Mediterranean and non
      Mediterranean regions subject to a high anthropogenic impact. ?PCBs, ?HCHs and
      HCB levels were negatively correlated with lipid content, while no such
      correlation was seen for ?DDTs. A significant correlation between levels and
      length and between levels and weight existed only for ?PCBs. The daily intake of
      PCBs and OCPs ingested by people living in Bizerte through the studied fish
      species was estimated and compared with those observed in other areas.

PMID- 23149189
TI  - Atmospheric emissions of F, As, Se, Hg, and Sb from coal-fired power and heat
      generation in China.
AB  - Coal is one of the major energy resources in China, with nearly half of produced
      Chinese coal used for power and heat generation. The large use of coal for power
      and heat generation in China may result in significant atmospheric emissions of
      toxic volatile trace elements (i.e. F, As, Se, Hg, and Sb). For the purpose of
      estimating the atmospheric emissions from coal-fired power and heat generation in
      China, a simple method based on coal consumption, concentration and emission
      factor of trace element was adopted to calculate the gaseous emissions of
      elements F, As, Se, Hg, and Sb. Results indicate that about 162161, 236, 637,
      172, and 33 t F, As, Se, Hg, and Sb, respectively, were introduced into
      atmosphere from coal combustion by power and heat generation in China in 2009.
      The atmospheric emissions of F, As, Se, Hg, and Sb by power and heat generation
      increased from 2005 to 2009 with increasing coal consumptions.

PMID- 23149190
TI  - Pilot trial evaluating the treatment of focal vitiligo with intralesional
      honeybee venom injection.

PMID- 23149192
TI  - Mercury and vitiligo.

PMID- 23149193
TI  - Wait times for Mohs micrographic surgery in Ottawa, Ontario.
AB  - BACKGROUND: The Ministry of Health and Long-Term Care, in coordination with
      Cancer Care Ontario, records and analyzes wait times for cancer surgery in the
      province of Ontario. However, this strategy does not include wait times for skin
      cancer surgery. PURPOSE: The wait times and referral patterns of patients
      undergoing Mohs micrographic surgery at The Ottawa Hospital (TOH) were examined
      to better assess the adequacy of access to skin cancer treatment in Ontario.
      METHOD: The records of 101 Mohs surgeries (96 patients) consecutively performed
      at TOH between June 14, 2010, and October 19, 2010, were reviewed. The interval
      between the date the referral for Mohs surgery was first received and the date of
      surgery was calculated for each case. The specialty of the referring physician
      and the postal code of each patient treated were also recorded. RESULTS: The
      average wait time between the date of referral and the date of surgery was 122.6
      days or 17.5 weeks (median 124 days, 17.7 weeks). Over 75% of patients waited
      over 12 weeks (84 days) for cancer surgery. All Mohs surgery patients treated at
      TOH resided within postal districts in eastern and northern Ontario. CONCLUSION:
      The current wait time for Mohs surgery in the Ottawa region is beyond the
      standard for cancer treatment. Improving access to care and incorporating Mohs
      surgery into the Ministry of Health and Long-Term Care's Wait Time Strategy might
      significantly improve this.

PMID- 23149194
TI  - Metachronous occurrence of colorectal cancer in a muir-torre syndrome patient
      presenting with recurrent sebaceous adenoma of the eyelid: case report and
      updated review of the literature.
AB  - BACKGROUND: Muir-Torre syndrome (MTS) is a rare genodermatosis considered a
      subtype of hereditary nonpolyposis colorectal cancer and traditionally associated
      with mutations in the mismatch repair genes. OBJECTIVE: We describe a 51-year-old
      male with primary manifestations of recurrent sebaceous adenoma of the upper
      eyelid, a positive cancer family history, and metachronous occurrence of
      colorectal cancer. METHOD: The diagnosis of MTS was established based on the
      clinical course, family history, and histopathologic findings, although further
      immunohistologic testing revealed the absence of MSH2 mutation. We additionally
      performed an updated summary of published MTS cases with sebaceous neoplasms
      originating from the eyelid and conjunctiva for the period 2005 to 2011.
      CONCLUSION: This patient, the second Greek case described in the international
      literature, is of interest mainly because of the metachronous occurrence of the
      visceral malignancy in combination with the absence of MSH2 mutation. The need
      for high clinical suspicion for MTS in cases with sebaceous lesions of the
      periocular region should therefore be reinforced regardless of the mutational
      screening test undertaken.

PMID- 23149195
TI  - Differentiation of rat dermal papilla cells into fibroblast-like cells induced by
      transforming growth factor beta1.
AB  - BACKGROUND: The origin of wound-healing fibroblasts is still debated. Dermal
      papilla cells (DPCs), which are an important population of stem cells for the
      regeneration of hair follicles, play a considerable role in cutaneous wound
      healing. Based on the plasticity of DPCs in wound healing, we hypothesized that
      DPCs may contribute to the fibroblast population of wound repair. OBJECTIVE: To
      explore the possibility of differentiation of DPCs into fibroblasts induced by
      transforming growth factor beta1 (TGF-beta1). METHODS: The fourth passage DPCs
      were treated with TGF-beta1 (10 ng/mL) for 4 days, and a series of methods was
      used to observe morphologic changes under an inverted phase contrast microscope,
      to validate the messenger ribonucleic acid expression change in alpha-smooth
      muscle actin (alpha-SMA) and vimentin by quantitative real-time reverse
      transcriptase polymerase chain reaction (QRT-PCR), to analyze the expression of
      alpha-SMA and vimentin protein by flow cytometry, and to semiquantitatively
      measure the expression of fibroblast-specific protein 1 (FSP1) by Western blot.
      RESULTS: DPCs treated with TGF-beta1 presented fibroblast-like changes in
      morphology and immunocytochemistry. The effects of TGF-beta1 on alpha-SMA and
      vimentin in DPCs were detected on both the transcriptional and the
      posttranscriptional levels. The results showed that TGF-beta1 significantly
      downregulated alpha-SMA expression and enhanced the expression of vimentin at all
      times tested. Further study revealed that TGF-beta1 could gradually promote the
      expression of FSP1 in a time-dependent manner. CONCLUSION: DPCs experienced the
      changes in molecular marker expression in response to TGF-beta1, which may be a
      key source of fibroblasts in wound healing.

PMID- 23149196
TI  - Etanercept improves quality of life outcomes and treatment satisfaction in
      patients with moderate to severe plaque psoriasis in clinical practice.
AB  - BACKGROUND: Etanercept is well tolerated and effective in moderate to severe
      psoriasis; however, data on patient-reported outcomes (PROs) in Canadian patients
      remain limited. OBJECTIVE: To assess PROs in Canadian patients with moderate to
      severe psoriasis receiving etanercept in an open-label trial more representative
      of general clinical practice than traditional research studies. METHODS: This 1
      year, multicenter, single-arm study enrolled 246 patients. Patients received
      etanercept 50 mg subcutaneously twice weekly for 3 months and then 50 mg once
      weekly for 9 months. Primary and safety end points were reported previously.
      Change from baseline to month 12 for the Dermatology Life Quality Index (DLQI),
      EuroQoL-5D, and Treatment Satisfaction Questionnaire for Medication (TSQM) are
      secondary outcomes reported here. Post hoc analyses of PROs are also reported.
      RESULTS: Mean +/- standard deviation (SD) DLQI total score improved from 13.7 +/-
      6.1 at baseline to 3.9 +/- 5.6 at month 12. By month 12, 75% of patients achieved
      a clinically meaningful improvement in the DLQI (>= 5-point improvement or a
      score of 0). Fifty-three to 86% of patients reported improvement or complete
      improvement in the six DLQI subscales. The mean +/- SD EuroQoL-5D total score
      improved from baseline (0.67 +/- 0.25) to month 12 (0.83 +/- 0.25). The TSQM
      scores showed improvement in global satisfaction, effectiveness, and convenience
      after 3 months. CONCLUSIONS: Etanercept was associated with improved PROs and
      increased treatment satisfaction over 1 year.

PMID- 23149197
TI  - Epidemiology of sebaceous carcinoma in Alberta, Canada, from 1988 to 2007.
AB  - BACKGROUND: The epidemiology of sebaceous carcinoma (SC) has not previously been
      examined in a Canadian population. OBJECTIVE: To determine the epidemiologic
      trends of SC in Alberta, Canada, from 1988 to 2007. METHODS: This study was a
      population-based, retrospective, epidemiologic analysis of SC in Alberta over a
      20-year span. RESULTS: Over the study period, the age-standardized SC incidence
      increased from 0.22 per 100,000 to 0.65 per 100,000. Sebaceous carcinoma is a
      cancer that predominantly affects the elderly (over 85% of cases were in persons
      60 years or older). Interestingly, the face (37.7% of cases), not the eyelids
      (26.2% of cases), was the most frequently affected site overall. Gender-specific
      trends reflected a slight male predominance (1.4:1) and significant differences
      in anatomic distribution between the sexes. CONCLUSION: For unexplained reasons,
      there has been a threefold increase in SC incidence in Alberta over the last two
      decades. In addition, there are significant gender-specific differences in the
      anatomic distribution of SC.

PMID- 23149198
TI  - Bilateral alar cartilage reduction rhinoplasty allows primary repair of alar
      defects in the bulbous nose.
AB  - BACKGROUND: Plastic surgeons have many reconstructive options for lower nasal
      skin defects, but given the unique aesthetic features of nasal skin the best
      source for reconstruction is nasal skin itself, when sufficient quantity exists.
      OBJECTIVE: The purpose of this study is to determine the outcome of bilateral
      alar cartilage reduction rhinoplasty in combination with a nasal flap to
      facilitate immediate reconstruction of defects of the nasal tip, soft triangle
      and alar margin. METHODS: This prospective study analyzed the aesthetic outcome
      after reconstruction with bilateral alar cartilage reduction rhinoplasty to
      reduce the nasal rim and create an excess of skin sufficient to facilitate
      immediate reconstruction of defects of the nasal tip, soft triangle and alar
      margin. RESULTS: All wounds healed primarily and patient satisfaction was
      achieved. CONCLUSION: Bilateral alar cartilage reduction rhinoplasty allows
      single-stage reconstruction of defects of the nasal tip, soft triangle, and
      medial alar rim in the bulbous nose. By placing incisions along the borders of
      the aesthetic subunits, this novel approach to primary reconstruction of the
      nasal tip, soft triangle, and medial alar rim provides skin with a superior color
      and texture match, maintains a satisfactory contour of the nasal rim, and
      optimizes the likelihood of good scar quality.

PMID- 23149199
TI  - Nerve involvement in granuloma annulare.
AB  - BACKGROUND: Nerve involvement developed in a patient with granuloma annulare, as
      evidenced by a perineural infiltrate of histiocytes in the dermis. The
      histopathologic pattern was suggestive of leprosy. No mycobacteria were observed,
      and neurologic testing was normal. OBJECTIVE: To determine whether inflammation
      of the nerves or perineural tissue is common in granuloma annulare, we studied
      the cutaneous nerves in skin biopsy specimens from 14 patients with granuloma
      annulare. METHODS: Sections were stained with hematoxylin-eosin to highlight
      inflammatory cells and with S-100 to identify cutaneous nerves. RESULTS: No
      inflammation around nerves was found in 12 specimens, abutting granulomatous
      inflammation was found in 1 specimen, and enveloping granulomatous inflammation
      was found in 1 specimen. No nerves were infiltrated by inflammatory cells.
      CONCLUSION: Perineural granulomatous inflammation resembling the perineural
      infiltrate of leprosy appears to be an uncommon characteristic of granuloma
      annulare. Clinical correlation and acid-fast stains can assist in establishing
      the correct diagnosis.

PMID- 23149200
TI  - Strongyloidiasis presenting as larva currens 38 years after presumed exposure.
AB  - BACKGROUND: We present a case of strongyloidiasis presenting as larva currens 38
      years after potential exposure in a country with what is typically thought of as
      low epidemiologic risk. CONCLUSION: This case highlights several important
      features of strongyloidiasis, including its varied epidemiology, long incubation
      period, and cutaneous manifestations.

PMID- 23149201
TI  - Linear segmental neurofibromatosis in an L5 distribution.
AB  - BACKGROUND AND OBJECTIVE: Neurofibromatosis (NF) is a neurocutaneous disorder
      with seven subtypes;segmental NF-1 is characterized by neurofibromas and or cafe
      au-lait macules in one or more dermatomes, primarily the thorax and abdomen. We
      present the rare case of a 36-year-old African-American female with isolated,
      multiple soft nodules in a linear configuration on the plantar and dorsal
      surfaces of the left foot. CONCLUSION: This is the first report of isolated
      segmental NF-1 in a unique linear pattern confined to the L5 dermatome.

PMID- 23149202
TI  - Isotretinoin for the treatment of granulomatous rosacea: case report and review
      of the literature.
AB  - BACKGROUND: Granulomatous rosacea is considered a clinical variant of rosacea and
      is characterized by hard yellow, brown, red or flesh-colored cutaneous papules or
      nodules that may be severe and may lead to scarring. The lesions typically appear
      on the cheeks and periorificial lesions; they are monomorphic in each patient and
      sit on relatively normal-appearing skin. The diagnosis should be established by
      excluding other granulomatous disorders and rosacea-like eruptions such as
      sarcoidosis, tuberculosis, and lupus miliaris disseminatus faciei. The clinical
      course is chronic and unpredictable, and management can be very difficult. CASE
      REPORT: We report the case of a 28-year-old female with granulomatous rosacea who
      responded successfully to oral isotretinoin. No recurrence was noticed 6 months
      after the completion of treatment.

PMID- 23149203
TI  - Erythema annulare centrifugum in a patient with crohn disease.
AB  - BACKGROUND: Erythema annulare centrifugum (EAC) represents a hypersensitivity
      reaction to a variety of conditions, many of which have been reported in the
      literature. METHODS AND RESULTS: We report on a 38-year-old woman with a 5-year
      history of recurrent polycylic, arcuate, scaly, erythematous patches with central
      clearing on her thighs and trunk. Clinical examination and biopsy were both
      consistent with a diagnosis of EAC. Two years after the initial presentation, she
      was diagnosed with mild Crohn disease. CONCLUSIONS: The prolonged nature of EAC
      in our patient and our inability to identify known associations of malignancies,
      including medications, connective tissue disorders, systemic disorders, and
      infections, led us to postulate that her EAC was related to her Crohn disease. A
      thorough review of the literature failed to detect any previous reports linking
      Crohn disease and EAC.

PMID- 23149204
TI  - Verrucous carcinoma due to arsenic ingestion in a psoriasis patient.
AB  - BACKGROUND AND OBJECTIVE: Verrucous carcinoma is a rare clinicopathologic entity
      caused by multifactorial influences. We report here a 64-year-old male patient
      presenting with a large exophytic mass in the right leg. RESULTS AND CONCLUSION:
      The patient had a 19-year duration of psoriasis and received various treatments.
      In his last year of life, he had been taking an illegally produced folk drug with
      the hope of controlling his psoriasis. However, 6 months after the drug
      ingestion, many papules appeared on his right leg, which eventually developed
      into a large tumor in the next few months. The patient died of acute pulmonary
      embolism only a week after hospitalization, when his tumor was pathologically
      confirmed as verrucous carcinoma. Later, the folk drug was analyzed and found to
      contain arsenic. The causative relevance of the tumor with his daily arsenic
      intake is discussed.

PMID- 23149205
TI  - Psoriasis vulgaris caused by ceramic inserts used in total hip replacement.
AB  - BACKGROUND: Ceramics are inorganic nonmetallic materials and are used as bioinert
      components in joint replacement surgeries. Ceramics are known to be low
      allergenic. We experienced a ceramic-induced psoriasis. OBJECTIVE: We report a
      first case of possible ceramic-induced psoriasis caused by a ceramic insert.
      METHODS: A 55-year-old female received an implanted ceramic-on-ceramic total hip
      replacement for osteoarthritis of the right hip joint. Following surgery, she
      developed psoriatic lesions, which continued for 10 years. We suspected that
      psoriasis was caused by a ceramic insert and removed it surgically. RESULTS: When
      the ceramic insert was replaced with a polyethylene-on-metal hip joint, the
      psoriatic lesions completely disappeared. CONCLUSION: The pathogenesis of
      psoriasis is still an enigma, although deregulation of nuclear factor kappaB
      signaling and resulting abnormal cytokine secretion are speculated to be
      involved. Ceramics may affect these signaling events and cause the onset of
      psoriasis.

PMID- 23149206
TI  - Pallor sign: an indicator of hemangioma in evolution.
AB  - BACKGROUND: The typical presentation of infantile hemangioma is well known and is
      easily recognizable. However, it may have many atypical presentations, as
      reported in the literature. Most of the hemangiomas are not visible at birth and
      become apparent at about 3 to 4 weeks of age. There are very few case reports of
      hemangioma presenting as a pale patch in the dermatology literature, and none of
      them describe the etiopathogenesis of this presentation and its clinical
      implications. OBJECTIVE AND CONCLUSION: We report a case of an infantile
      hemangioma with a trichrome presentation: an erythematous oval patch with a dark
      red macule at the periphery enclosed by a hypopigmented halo. A brief description
      of the etiopathogenesis of the pallor sign is also given.

PMID- 23149207
TI  - Hypertrophic and ulcerated discoid lupus erythematosus.
AB  - BACKGROUND: Hypertrophic lupus is an uncommon clinical variant of chronic
      cutaneous lupus that remains a challenge to treat. A 45-year-old female day-care
      worker with long-standing lupus presented with hypertrophic cutaneous involvement
      on the dorsal hand, elbow, and toe of 6 years' duration. Treatments included
      monotherapy with either hydroxychloroquine or chloroquine and potent topical and
      intralesional steroid injection. Systemic chemotherapy with R-CHOP chemotherapy
      for stage IIA diffuse large B-cell lymphoma did not clear the skin findings.
      OBJECTIVE: To review the clinical presentation and treatment of hypertrophic
      lupus. This report documents clinical improvement in refractory hypertrophic
      lupus with a regimen of acitretin and combination antimalarial therapy. METHODS:
      The available published literature on the treatment of hypertrophic lupus was
      reviewed. There is limited published experience combining retinoids and
      antimalarials for the treatment of refractory lupus. Combination therapy with two
      antimalarials (ie, quinacrine with either hydroxychloroquine or chloroquine)
      provides therapeutic benefit for resistant cutaneous disease. In this case,
      triple therapy with two antimalarials and an oral retinoid achieved clinical
      clearance relatively rapidly, and this effect was maintained over a year.
      RESULTS: This article reports successful treatment of refractory hypertrophic
      discoid lupus with combination therapy that included chloroquine 250 mg/d,
      quinacrine 100 mg/d, and actitretin 25 mg/d. CONCLUSION: This report suggests
      that combination therapy using two antimalarials and an oral retinoid is a
      consideration for refractory hypertrophic lupus, but further study is warranted.

PMID- 23149208
TI  - Treatment of ulcerative necrobiosis lipoidica with topical calcineurin inhibitor:
      case report and literature review.
AB  - BACKGROUND: Ulcerative necrobiosis lipoidica (UNL) is an uncommon disease, which
      is frequently recalcitrant to available therapies. It is characterized by well
      defined, ulcerated plaques with indurated borders and atrophic centers. Multiple
      therapeutic options have been described, with variable success rates. OBJECTIVE:
      To report the efficacy of using topical tacrolimus in treating UNL. METHOD:
      Topical tacrolimus was used in the treatment of two patients with UNL. RESULT:
      Topical tacrolimus is effective in treating UNL. CONCLUSION: Topical tacrolimus
      is a reasonably effective choice in treating UNL.

PMID- 23149209
TI  - Intralesional cidofovir in the treatment of cutaneous warts in a renal transplant
      patient.
AB  - BACKGROUND: Cutaneous warts are often recalcitrant to conventional therapy in
      immunocompromised patients. Cidofovir is a potent antiviral agent shown to have a
      broad spectrum of action against DNA virus, including human papillomavirus.
      OBJECTIVE: To determine the efficacy of intralesional cidofovir in the treatment
      of florid warts in an immunocompromised renal transplant patient. METHOD: The
      patient received seven injections of intralesional cidofovir at 4 week intervals
      in his numerous palmar warts. CONCLUSION: Based on our results, intralesional
      cidofovir is a promising therapeutic modality in the treatment of cutaneous warts
      in the renal transplant population.

PMID- 23149210
TI  - Use of a perimeter technique with Mohs micrographic surgery in the resection of a
      giant basal cell carcinoma.
AB  - BACKGROUND: Giant basal cell carcinomas (GBCC) can demonstrate very malignant
      behavior and pose a surgical challenge. OBJECTIVE: To present a surgical
      technique utilizing Mohs and the resection of narrow bands of tissue to excise a
      GBCC that created a large facial defect of 5 cm * 2 cm. METHODS: A unique
      combination of Mohs micrographic surgery and the recently described perimeter
      techniques used for lentigo maligna were used to resect the tumor. RESULTS: This
      hybrid technique was tissue sparing and therefore helped prevent the
      complications associated with a larger resection and allowed for an easier
      reconstruction. At 2 months post resection the patient had no known metastasis or
      tumor recurrence. CONCLUSION: This case highlights the importance of early
      recognition of basal cell carcinoma and the complications that can arise when
      lesions are left untreated for a long duration. Also, we describe a surgical
      technique that could help reduce the complications associated with these large
      tumors.

PMID- 23149211
TI  - How to achieve international action on falsified and substandard medicines.

PMID- 23149212
TI  - Letter to the editor regarding: Brown SD, Ecker JL, Ward JRM, et al.

PMID- 23149213
TI  - The impairment of the High Mobility Group A (HMGA) protein function contributes
      to the anticancer activity of trabectedin.
AB  - Trabectedin (Ecteinascidin-743 or ET-743) is a novel antitumour agent of marine
      origin with potent antitumour activity both in vitro and in vivo. It interacts
      with the minor groove of DNA, interfering with transcriptional activity and DNA
      repair pathways. Here, we report a novel mechanism by which trabectedin exerts
      its cytotoxic effects on carcinoma cells. It is based on its ability to impair
      the function of the High-Mobility Group A (HMGA) proteins. These proteins have a
      key role in cell transformation, and their overexpression is a common feature of
      human malignant neoplasias, representing a poor prognostic index often correlated
      to anti-cancer drug resistance. They bind the minor groove of DNA, alter
      chromatin structure and, thus, regulate the transcription of several genes by
      enhancing or suppressing the activity of transcription factors. We first report
      that trabectedin has a higher cytotoxic effect on thyroid and colon carcinoma
      cells expressing abundant levels of HMGAs in comparison with cells not expressing
      them. Then, we have shown that trabectedin treatment displaces HMGA proteins from
      the HMGA-responsive promoters, including ATM promoter, impairing their
      transcriptional activity. Finally, we report a synergism between Ionising
      Radiations and trabectedin treatment restricted to the HMGA-overexpressing cancer
      cells. This result might have important clinical implications since it would
      suggest the use of trabectedin for the treatment of neoplasias expressing
      abundant HMGA levels that are frequently associated to chemoresistance and poor
      prognosis.

PMID- 23149214
TI  - Initial development of a questionnaire evaluating perceived benefits and barriers
      to pediatric clinical trials participation.
AB  - OBJECTIVE: To evaluate perceived benefits and barriers to pediatric clinical
      trials participation to improve decision-making and enhance recruitment and
      retention among minority youth with chronic health conditions (sickle cell
      disease, asthma) and their caregivers. METHODS: A questionnaire was developed
      based on the social ecological model using input from medical experts and
      community-based public health organizations. Parallel caregiver, adolescent/young
      adult (AYA; 16-39 years old), and child (8-15 years old) versions were field
      tested. Patients and caregivers completed the questionnaire, which included
      demographic items, perceived life stress and social desirability measures.
      RESULTS: Exploratory factor analysis rendered a four-factor solution for the
      caregiver version (direct treatment benefit, mistrust of research/researchers,
      trust in healthcare team to engage in safe research, and opportunity cost) and
      the AYA version (mistrust/no direct benefit, safety, direct treatment
      benefit/practical considerations, and social support for research). Factor
      structures differed for SCD and asthma caregivers; results were equivocal for the
      child version. Summated subscales were not significantly associated with patient
      demographics or social desirability, but significant correlations with perceived
      life stress and prior participation in research were identified. CONCLUSIONS:
      While the factor structure should be confirmed with larger samples, findings
      indicate potential benefit, perceived harm due to mistrust of researchers, and
      logistics are primary factors in decision-making about participation in pediatric
      clinical trials. By addressing these benefits/barriers through adjustments to
      recruitment and informed consent procedures, researchers may address
      misperceptions of research, improve decision-making, and increase recruitment and
      retention particularly for ethnic minority children with chronic health
      conditions.

PMID- 23149215
TI  - European Commission updates rules on clinical trials.

PMID- 23149216
TI  - Obesity and intermittent hypoxia increase tumor growth in a mouse model of sleep
      apnea.
AB  - BACKGROUND: Intermittent hypoxia and obesity which are two pathological
      conditions commonly found in patients with obstructive sleep apnea (OSA),
      potentially enhance cancer progression. OBJECTIVE: To investigate whether obesity
      and/or intermittent hypoxia (IH) mimicking OSA affect tumor growth. METHODS: A
      subcutaneous melanoma was induced in 40 mice [22 obese (40-45g) and 18 lean (20
      25g)] by injecting 10(6) B16F10 cells in the flank. Nineteen mice (10 obese/9
      lean) were subjected to IH (6h/day for 17days). A group of 21 mice (12 obese/9
      lean) were kept under normoxia. At day 17, tumors were excised, weighed and
      processed to quantify necrosis and endothelial expression of vascular endothelial
      growth factor (VEGF) and CD-31. VEGF in plasma was also assessed. RESULTS: In
      lean animals, IH enhanced tumor growth from 0.81+/-0.17 to 1.95+/-0.32g. In obese
      animals, a similar increase in tumor growth (1.94+/-0.18g) was observed under
      normoxia, while adding IH had no further effect (1.69+/-0.23g). IH only promoted
      an increase in tumoral necrosis in lean animals. However, obesity under normoxic
      conditions increased necrosis, VEGF and CD-31 expression in tumoral tissue.
      Plasma VEGF strongly correlated with tumor weight (rho=0.76, p<0.001) in the
      whole sample; it increased in lean IH-treated animals from 66.40+/-3.47 to
      108.37+/-9.48pg/mL, p<0.001), while the high baseline value in obese mice
      (106.90+/-4.32pg/mL) was unaffected by IH. CONCLUSIONS: Obesity and IH increased
      tumor growth, but did not appear to exert any synergistic effects. Circulating
      VEGF appeared as a crucial mediator of tumor growth in both situations.

PMID- 23149217
TI  - Nocturnal sleep, daytime sleepiness and fatigue in fibromyalgia patients compared
      to rheumatoid arthritis patients and healthy controls: a preliminary study.
AB  - OBJECTIVE: Fibromyalgia (FM) and rheumatoid arthritis (RA) are pain disorders,
      both of which are associated with complaints of sleep disturbance, non-refreshing
      sleep, and daytime sleepiness and fatigue. Given the putative differential
      central versus peripheral nervous system involvement in these disorders,
      subjective and objective measures of nocturnal sleep, daytime sleepiness, fatigue
      and pain were compared between patient groups and to healthy controls (HC).
      METHODS: Fifty women (18 with FM, 16 with RA, and 16 HC) completed an 8h
      nocturnal polysomnogram (NPSG), Multiple Sleep Latency Test (MSLT) the following
      day, and self-reports of sleepiness, fatigue, and pain. RESULTS: FM and RA
      patients were similar to each other and had less total sleep time than HC,
      primarily due to more wake after sleep onset. In an analysis of sleep and wake
      bouts, both patient groups had longer duration of wake bouts than HC. Nocturnal
      sleep was judged to be non-restorative for both patient groups. Although
      reporting the greatest subjective sleepiness and fatigue, FM patients had less
      objective (MSLT) daytime sleepiness than HC, whereas RA patients were
      intermediate in objective sleepiness. Unlike the RA and HC, FM patients also
      showed no association between their subjective and objective sleepiness.
      CONCLUSIONS: Women with FM have similar nocturnal sleep disturbance as those with
      RA, but FM patients report greater self-rated daytime sleepiness and fatigue than
      RA and HC, which did not correspond to the relatively low level of objectively
      determined daytime sleepiness of FM patients. These findings suggest a
      generalized hyperarousal state in FM.

PMID- 23149218
TI  - Clinical and histological prognostic factors in locally advanced oral cavity
      cancers treated with primary surgery.
AB  - OBJECTIVE: The primary objective of this study was to determine the clinical and
      pathological prognostic factors in locally advanced oral cavity cancers treated
      by primary surgery. METHODS: All patients treated by primary surgery with free
      flap reconstruction for locally advanced oral cavity squamous cell carcinoma in
      our institution between 2000 and 2010 were included in this retrospective study.
      Overall, cause-specific and locoregional disease-free survivals were determined
      by Kaplan-Meier analyses. Clinical and histological prognostic factors were
      assessed by univariate (Log Rank tests) and multivariate (Cox models) analyses.
      RESULTS: A total of 149 patients (102 men and 47 women; mean age=61.3+/-12.1
      years) were included in the study. Five-year overall, cause-specific and
      locoregional disease-free survivals were 55%, 68% and 71%, respectively. Age,
      comorbidity and tumour size (histological evaluation) were significantly
      correlated with overall survival (P<0.05). Age, tumour size, bone invasion and
      surgical margins were significantly correlated with locoregional disease-free
      survival (P<0.05). CONCLUSION: The main prognostic factors identified in this
      study were clinical (age and comorbidity) and histological (pathological tumour
      size, bone invasion and surgical margins).

PMID- 23149219
TI  - Evaluation of hypermethylation and expression pattern of GMR2, GMR5, GMR8, and
      GRIA3 in patients with schizophrenia.
AB  - Emerging evidence suggests a role of dysfunction of glutamatergic
      neurotransmission and its receptors in the pathophysiology of schizophrenia
      (SCZ). This study evaluated whether the promoter hypermethylation and RNA
      expression pattern of GMR2 (glutamate metabotropic receptor), GMR5, GMR8, and
      GRIA3 (glutamate receptor, ionotropic alpha-amino-3-hydroxy-5-methyl-4-isoxazole
      propionic acid) are associated with the risk of schizophrenia between
      schizophrenia patients and healthy controls. MATERIALS AND METHODS: Methylation
      specific polymerase chain reaction (MS-PCR) was used to estimate the promoter
      hypermethylation of GMR2, GMR5, GMR8, and GRIA3 genes on 81 isolated genomic DNA
      samples from the peripheral blood of individuals with schizophrenia and 71
      healthy control subjects. In addition, real-time reverse transcription-PCR was
      used to estimate mRNA levels in 34 blood samples of healthy controls and cases.
      RESULTS: The methylation of GRM2 and GRM5 greatly decreased the risk of
      schizophrenia in comparison to the reference unmethylated pattern [OR=0.38, 95%
      CI; 0.144-1.035, p=0.05; OR=0.06, 95% CI; 0.007-0.54.10, p=0.01], respectively.
      The methylation of GRIA3 highly increased the risk of schizophrenia, but non
      significant (OR=2.3, 95% CI; 0.51-10.42). The outcomes of the expression analysis
      revealed a statistically significant difference between the cases (n=17) and
      healthy controls (n=17) regarding the relative gene expression of GRM2, GRM5, and
      GRIA3 (p=0.0001). CONCLUSION: To the best of our knowledge, this is the first
      evidence showing that the promoter methylation of the GMR2 and GMR5 genes greatly
      decreased the risk of schizophrenia, and the expression level of the GRM2, GRM5,
      and GRIA3 genes increased significantly in patients in comparison to healthy
      controls. These outcomes suggest that there is a need for more attention to be
      paid to the effect of epigenetic variations in the development of SCZ in further
      investigations.

PMID- 23149221
TI  - The state of simulation in endoscopy education: continuing to advance toward our
      goals.

PMID- 23149222
TI  - Correlation between the grain orientation dependence of color etching and
      chemical etching.
AB  - A gray cast iron specimen was investigated by color and chemical etching with
      optical and atomic force microscopy, and the effect of grain orientation on the
      effectiveness of etching was examined. It was proven that the grain orientation
      dependence of chemical and color etching is just the opposite, and that the
      specimen surface after color etching is not uniformly smooth. Explanation for the
      layer structure of the color etched iron specimen is given.

PMID- 23149220
TI  - Pro-angiogenic activity of TLRs and NLRs: a novel link between gut microbiota and
      intestinal angiogenesis.
AB  - BACKGROUND & AIMS: In intestinal inflammation the gut microbiota induces an
      innate immune response by activating epithelial and immune cells that initiate or
      maintain inflammation. We investigated whether the microbiota also can activate
      local microvascular cells and induce angiogenesis. METHODS: Human intestinal
      microvascular endothelial cells (HIMEC) and human intestinal fibroblasts (HIF)
      were exposed to bacterial ligands specific for Toll-like receptor (TLR)2/6 and 4,
      and NOD1 and NOD2, and cell proliferation, migration, transmigration, tube
      formation, and production of pro-angiogenic factors were measured. The ability of
      the ligands to induce ex vivo vessel sprouting in an aortic ring assay and in
      vivo angiogenesis using a collagen gel assay also were assessed. RESULTS:
      Bacterial ligands induced proliferation, migration, transmigration, tube
      formation of HIMEC, vessel sprouting, and in vivo angiogenesis; they also
      stimulated production of angiogenic factors from HIMEC and HIF, and HIF-derived
      angiogenic factors promoted HIMEC proliferation. To various degrees, all ligands
      induced angiogenic responses, but these were ligand- and cell type-dependent.
      Responses were mediated through receptor interacting protein-2 (RIP2)- and tumor
      necrosis factor receptor-associated factor 6 (TRAF6)-dependent signaling,
      involved the mitogen-activated protein kinase (MAPK) and nuclear factor-kappaB
      (NF-kappaB) pathways and the up-regulation of vascular endothelial growth factor
      receptor 2 (VEGF-R2) and focal adhesion kinase (FAK). Knockdown of RIP2 and TRAF6
      by RNA interference and neutralization of interleukin-8, basic fibroblast growth
      factor, and vascular endothelial growth factor inhibited TLR-/NOD-like receptor
      induced HIMEC angiogenesis. CONCLUSIONS: The gut microbiota can selectively
      activate mucosal endothelial and mesenchymal cells to promote specific angiogenic
      responses in a TLR- and NOD-like receptor-dependent fashion. This innate immunity
      mediated response may expand the mucosal microvascular network, foster immune
      cell recruitment, and contribute to chronic intestinal inflammation.

PMID- 23149223
TI  - Facial emotion recognition in borderline personality disorder.
AB  - BACKGROUND: Emotion dysregulation represents a core symptom of borderline
      personality disorder (BPD). Deficits in emotion perception are thought to
      underlie this clinical feature, although studies examining emotion recognition
      abilities in BPD have yielded inconsistent findings. Method The results of 10
      studies contrasting facial emotion recognition in patients with BPD (n = 266) and
      non-psychiatric controls (n = 255) were quantitatively synthesized using meta
      analytic techniques. RESULTS: Patients with BPD were less accurate than controls
      in recognizing facial displays of anger and disgust, although their most
      pronounced deficit was in correctly identifying neutral (no emotion) facial
      expressions. These results could not be accounted for by speed/accuracy in the
      test-taking approach of BPD patients. CONCLUSIONS: Patients with BPD have
      difficulties recognizing specific negative emotions in faces and may misattribute
      emotions to faces depicting neutral expressions. The contribution of state
      related emotion perception biases to these findings requires further
      clarification.

PMID- 23149224
TI  - Enhanced tumor growth after portal vein embolization in a rabbit tumor model.
AB  - BACKGROUND: Preoperative portal vein embolization (PVE) is used to increase
      future remnant liver volume through induction of hepatocellular regeneration.
      This event, however, potentially enhances tumor growth. The aim of our study was
      to assess tumor growth and liver regeneration after PVE in a rabbit hepatic tumor
      model. The VX2 carcinoma is derived from a virus-induced papilloma tumor in
      rabbits. The tumor grows rapidly, and its blood supply is similar to that of
      human hepatocellular carcinoma. MATERIALS AND METHODS: Two weeks after
      subcapsular implantation of a VX2 carcinoma in the cranial liver lobe, New
      Zealand White rabbits were allocated to a control or PVE group (n = 5 per group).
      In the PVE group, the portal vein branch to the cranial liver lobes (80%) was
      embolized using particles and coils, leaving the caudal liver lobe (20%) free. In
      the tumor control group, the liver was mobilized. Computed tomography volumetry
      was performed on days 3, 7, 10, and 14. Tumor growth rate (TGR), hepatocellular
      proliferation rate, and liver damage parameters were assessed before PVE and on
      days 1, 3, 7, 10, and 14. RESULTS: Portography confirmed complete occlusion of
      the portal vein branch to the cranial liver lobes in all PVE rabbits. The
      hypertrophy response and proliferation rate in the nonembolized liver lobes were
      significantly higher in the PVE group, which was confirmed by liver-to-body
      weight index assessment. TGR was increased in both groups, with a significantly
      larger increase in the PVE group over time (day 14: mean, 34.4 +/- 4.3 mL/d
      versus control: mean, 24.1 +/- 7.2 mL/d; P < 0.05). CONCLUSIONS: TGR was
      significantly increased after PVE in the rabbit tumor model. This finding
      supports the notion that PVE potentially enhances tumor growth, along with the
      regeneration of the nonembolized liver lobe.

PMID- 23149226
TI  - Kinematics of bipedal locomotion while carrying a load in the arms in bearded
      capuchin monkeys (Sapajus libidinosus).
AB  - Understanding the selective pressures that drove the evolution of bipedalism in
      the human lineage may help inform researchers about the locomotor mode(s) of pre
      hominin ancestors. Several selective pressures have been hypothesized, including
      the need to carry food, tools, or infants. Bearded capuchin monkeys are an
      excellent primate in which to examine the hypothesis that carrying supported the
      evolution of bipedalism because they are morphologically generalized and in some
      ways similar to Miocene hominoids, from which the transitional biped evolved.
      Additionally, bearded capuchins regularly move bipedally while carrying tools
      that represent a significant portion of their body mass. Here, we examined the
      spatio-temporal and kinematic gait parameters in a wild setting of Sapajus
      libidinosus moving bipedally while carrying a stone tool, as well as unloaded
      bipedal tufted capuchins in the lab. Results indicate that compared with humans,
      the monkeys move with a more bent-hip, bent-knee posture during both types of
      bipedalism, as expected. Few differences exist in spatio-temporal or kinematic
      parameters within species across load-carrying and unloaded bipedalism. The
      capuchin ankle, however, during load-carrying goes through a greater range of
      motion in relatively less time than both humans and unloaded capuchins. Data from
      this study provide the first quantitative data on bipedalism during load-carrying
      by wild primates in a natural setting. As such, they are a useful comparative
      reference for understanding bipedalism, particularly during load-carrying.

PMID- 23149225
TI  - Change in sense of coherence (SOC) and symptoms of depression among old non
      demented persons 12 months after hospitalization.
AB  - We studied whether SOC of older adults (>=65 years) without cognitive impairment
      had changed 1-year after medical hospitalization (T2) and to examine what factors
      were associated with the change. At baseline (T1) and (T2), the 13-item version
      of the SOC scale assessed coping, and the Hospital Anxiety and Depression (HAD)
      Scale assessed symptoms of depression and anxiety. The cognitive state was
      assessed by means of the mini-mental state examination (MMSE). Physical health
      was measured with the Charlson Index and functional status with Lawton and
      Brody's scales for physical self-maintenance (PSMS) and the instrumental
      activities of daily living (I-ADL). In all, 97 (51 men) persons with a mean age
      of 75.3 (SD 6.3) years and Mini Mental State Evaluation (MMSE) score of 28.0 (SD
      1.6) participated. The SOC improved significantly from baseline to 1-year later
      (mean 76.5, SD 11.4 vs. mean 79.1, SD 9.1, p<=0.01). Improved SOC was associated
      with a low SOC at baseline and living without assistance during the study period.
      The prevalence of depression (HAD-D>=8) and the mean depression (HAD-D) score did
      not change between the first and second data collection (HAD-D>=8: 3.1% vs. 4.1%
      and HAD-D score: mean 1.8, SD 2.3 vs. mean 2.4, SD 2.4). However, an improved SOC
      and reduced anxiety symptoms at the second time point were associated with
      reduced HAD-D. The mean SOC improved 1-year after hospitalization. The symptoms
      of depression did not change, but reduction of symptoms of depression at the
      second time point was associated with improved SOC.

PMID- 23149227
TI  - Flavonoid glycosides from the leaves of Allium victorialis var. platyphyllum and
      their anti-neuroinflammatory effects.
AB  - Eight new flavonoid glycosides, named allivictoside A-H (1-8), together with
      twelve known flavonoids (9-20) were isolated from the leaves of Allium
      victorialis var. platyphyllum. The structures of 1-8 were determined by chemical
      and spectroscopic methods, including 1D, 2D NMR analyses and HR-MS. To evaluate
      the anti-neuroinflammatory activities of all isolates, we measured the secreted
      nitric oxide levels in murine microglia BV-2 cells stimulated by
      lipopolysaccharide. In this study, compounds 2, 6, 10, and 18 significantly
      inhibited nitric oxide production (IC(50) values of 20.67, 20.42, 21.48 and 19.80
      MUM, respectively) without cell toxicity. Therefore, we suggest that
      allivictoside B (2) and F (6), 3-O-beta-D-glucosyl-7-O-beta-D-(2-O
      feruloyl)glucosylkaempferol (10) and quercetin 3-O-beta-d-glucopyranoside (18)
      may be considered as candidates for the treatment of diseases associated with
      neuroinflammation.

PMID- 23149228
TI  - Discovery of selective biaryl ethers as PDE10A inhibitors: improvement in potency
      and mitigation of Pgp-mediated efflux.
AB  - We report the discovery of a novel series of biaryl ethers as potent and
      selective PDE10A inhibitors. Structure-activity studies improved the potency and
      decreased Pgp-mediated efflux found in the initial compound 4. X-ray
      crystallographic studies revealed two novel binding modes to the catalytic site
      of the PDE10A enzyme.

PMID- 23149229
TI  - 6,7-Dihydroxy-1-oxoisoindoline-4-sulfonamide-containing HIV-1 integrase
      inhibitors.
AB  - Although an extensive body of scientific and patent literature exists describing
      the development of HIV-1 integrase (IN) inhibitors, Merck's raltegravir and
      Gilead's elvitegravir remain the only IN inhibitors FDA-approved for the
      treatment of AIDS. The emergence of raltegravir-resistant strains of HIV-1
      containing mutated forms of IN underlies the need for continued efforts to
      enhance the efficacy of IN inhibitors against resistant mutants. We have
      previously described bicyclic 6,7-dihydroxyoxoisoindolin-1-ones that show good IN
      inhibitory potency. This report describes the effects of introducing substituents
      into the 4- and 5-positions of the parent 6,7-dihydroxyoxoisoindolin-1-one
      platform. We have developed several sulfonamide-containing analogs that enhance
      potency in cell-based HIV assays by more than two orders-of-magnitude and we
      describe several compounds that are more potent than raltegravir against the
      clinically relevant Y143R IN mutant.

PMID- 23149230
TI  - The discovery of a novel series of glucokinase activators based on a
      pyrazolopyrimidine scaffold.
AB  - Glucokinase is a key enzyme in glucose homeostasis since it phosphorylates
      glucose to give glucose-6-phosphate, which is the first step in glycolysis. GK
      activators have been proven to lower blood-glucose, and therefore have potential
      as treatments for type 2 diabetes. Here the discovery of pyrazolopyrimidine GKAs
      is reported. An original singleton hit from a high-throughput screen with
      micromolar levels of potency was optimised to give compounds with nanomolar
      activities. Key steps in this success were the introduction of an extra side
      chain, which increased potency, and changing the linking functionality from a
      thioether to an ether, which led to improved potency and lipophilic ligand
      efficiency. This also led to more stable compounds with improved profiles in
      biological assays.

PMID- 23149231
TI  - A pull-down method with a biotinylated bait protein prepared by cell-free
      translation using a puromycin linker.
AB  - In this paper, we demonstrate a novel pull-down method that dramatically reduces
      the cost and preparation time of a bait protein by cell-free translation with a
      puromycin linker. With the C-terminus of the bait protein linked to biotin
      through a puromycin molecule after the translation reaction and subsequent mRNA
      degradation by RNase, the prey protein was easily pulled down by streptavidin
      coated magnetic beads in a test tube. Three fluorescent prey protein types were
      tested and confirmed by gel electrophoresis to be pulled down easily and rapidly,
      depending on their affinity.

PMID- 23149232
TI  - Whole-mount in situ detection of microRNAs on Arabidopsis tissues using Zip
      Nucleic Acid probes.
AB  - MicroRNAs (miRNAs) affect fundamental processes of development. In plants miRNAs
      regulate organ development, transition to flowering, and responses to
      abiotic/biotic stresses. To understand the biological role of miRNAs, in addition
      to identifying their targeted transcripts, it is necessary to characterize the
      spatiotemporal regulation of their expression. Many methods have been used to
      define the set of organ-specific miRNAs by tissue dissection and miRNA profiling
      but none of them can describe their tissue and cellular distribution at the high
      resolution provided by in situ hybridization (ISH). This article describes the
      setup and optimization of a whole-mount ISH protocol to target endogenous miRNAs
      on intact Arabidopsis seedlings using DIG-labeled Zip Nucleic Acid (ZNA)
      oligonucleotide probes. Automation of the main steps of the procedure by
      robotized liquid handling has also been implemented in the protocol for best
      reproducibility of results, enabling running of ISH experiments at high
      throughput.

PMID- 23149233
TI  - Tryptase disturbs endocytic allergen degradation in intestinal epithelial cells.
AB  - It is noticed that mast cell activation can compromise epithelial barrier
      function, enabling antigens to be transported to the deep tissue of the
      intestine; the underlying mechanism is to be further elucidated. The current
      study aimed to investigate the mechanism by which the mast cell-derived mediator,
      tryptase, interferes with the degradation of the endocytic antigen in the
      intestinal epithelial cells. Intestinal epithelial cell lines were cultured into
      monolayers. The transepithelial resistance (TER) and permeability were assessed.
      The fusion of endosome and lysosome in epithelial cells was observed by
      immunocytochemistry. The antigenicity of protein antigens was tested by flow
      cytometry. The results showed that the expression of ubiquitin E3 ligase A20
      (A20) was weakly expressed by naive gut epithelial cells and was markedly
      suppressed on exposure to tryptase in the culture. The presence of tryptase
      greatly disturbed the fusion of antigen-carrying endosomes and lysosomes in the
      epithelial cells, resulting in epithelial barrier dysfunction and a large
      quantity of antigen with functional antigenicity to be transported across the
      epithelial barrier. We conclude that tryptase can suppress the production of A20
      in the intestinal epithelial cell lines, playing a critical role in intestinal
      epithelial monolayer barrier dysfunction.

PMID- 23149234
TI  - A zinc finger nuclease assay to rapidly quantitate homologous recombination
      proficiency in human cell lines.
AB  - Homologous recombination (HR) is a cellular mechanism for accurate repair of
      double-strand DNA breaks, often deregulated in cancer. Development of novel
      cancer therapeutics targeting HR pathways would benefit from a quantitative and
      rapid means of measuring HR. Here, we describe a zinc finger nuclease (ZFN) assay
      that can quantify HR. Knockdown of BRCA1 or inactivation of BRCA2 decreased HR
      activity in cells, whereas gene restoration induced activity 8-fold. HR activity
      was also reflective of BRCA1/2 status in cells with known endogenous mutations.

PMID- 23149235
TI  - Development of a microarray detection method for galectin cancer proteins based
      on ligand binding.
AB  - In this article, we describe the development of a novel detection method for the
      visualization of ligand-binding proteins. Current proteomic tools, such as the
      enzyme-linked immunosorbent assay (ELISA), are based on protein abundance rather
      than protein activity and can result in conflicting data. To address this issue,
      we developed an assay in which ligand binding is detected using a microarray
      approach with immobilized antibodies on a porous aluminum oxide matrix. The
      galectin family of proteins was used as a model system to evaluate the
      performance of this approach. Galectins selectively bind galactosides and are
      linked to cancer progression. Our assay employed antibodies directed against
      different galectins. The antibodies were immobilized on the microarray surface by
      use of protein A/G. In our example, galectin-1 and galectin-9 were then detected
      in cell lysates. Lysates were exposed to the anti-galectin surface, followed by
      washing and quantification with a general fluorescent galectin ligand. The
      optimal galectin ligand allowed detection of nanogram amounts of galectin using
      only 1 MUg of antibody. Galectin-1 was visualized in HeLa and tumor cell lysates,
      indicating the potential of the method for a clinical setting.

PMID- 23149236
TI  - Working and learning: post-registration student midwives' experience of the
      competency assessment process.
AB  - AIM: to explore student midwives experiences of the Clinical Competency
      Assessment process utilised on the Higher Diploma in Midwifery (18 month)
      programme. BACKGROUND: the assessment of clinical skills and practice has
      traditionally been an integral part of midwifery educational programmes; however
      the method of clinical assessment has changed and developed. Similar to other
      countries, in Ireland assessment of clinical practice is achieved through the
      utilisation of a broad competency framework provided by the regulatory body, An
      Bord Altranais (2005) which is yet to be evaluated from a midwifery perspective.
      METHOD: a descriptive qualitative study was undertaken once ethical approval had
      been granted by the University's Ethics Committee. All student midwives (n=20) in
      one cohort were invited to participate and nine students were interviewed.
      Interviews were tape recorded. Data were analysed using Burnard's (2006)
      framework. FINDINGS: the process of competency assessment was perceived by many
      of the students to facilitate continuous assessment of clinical practice but
      there were issues in relation to the language and the number of competencies to
      be assessed. There were challenges also associated with the written evidence
      required as part of the assessment with many of the students questioning the
      usefulness of this in a clinical assessment. A variety of supports were
      identified and utilised by the students. Continuity and availability of
      preceptors were noted to be factors impacting on completion of the assessment as
      were the competing demands of clinical care. RECOMMENDATIONS: the findings of
      this small study are congruent with much of the international literature focusing
      on clinical competency models. Consideration needs to be given to identifying and
      integrating into practice, a clearly defined process for competency assessment,
      by all the relevant stakeholders. An opportunity for feedback throughout the
      process is considered very significant and the mechanism for this needs to be
      made explicit in any competency assessment documentation Competency documentation
      currently in use needs to be reviewed in light of the findings of this study and
      the rationale for inclusion of a written evidence component needs to be carefully
      considered. Further research is warranted in relation to the effectiveness of the
      competency tool in assessing competency in practice.

PMID- 23149237
TI  - A review of cultural influence on maternal mortality in the developing world.
AB  - OBJECTIVE: identify research examining the effect of culture on maternal
      mortality rates. DESIGN: literature review of CINAHL, Cochrane, PsychInfo, OVID
      Medline and Web of Science databases. SETTING: developing countries with
      typically higher rates of maternal mortality. PARTICIPANTS: women, birth
      attendants, family members, nurse midwives, health-care workers, and community
      members. MEASUREMENTS AND FINDINGS: reviews, qualitative and mixed-methods
      research have identified components of culture that have a direct impact on
      maternal mortality. Examples of culture are given in the text and categorised
      according to the way in which they impact maternal mortality. KEY CONCLUSIONS:
      cultural customs, practices, beliefs and values profoundly influence women's
      behaviours during the perinatal period and in some cases increase the likelihood
      of maternal death in childbirth. The four ways in which culture may increase MMR
      are as follows: directly harmful acts, inaction, use of care and social status.
      IMPLICATIONS FOR PRACTICE: understanding the specifics of how the culture
      surrounding childbirth contributes to maternal mortality can assist nurses,
      midwives and other health-care workers in providing culturally competent care and
      designing effective programs to help decrease MMR, especially in the developing
      world. Interventions designed without accounting for these cultural factors are
      likely to be less effective in reducing maternal mortality.

PMID- 23149238
TI  - What can qualitative studies tell us about the experiences of women who are
      pregnant that have an eating disorder?
AB  - OBJECTIVE: pregnancy is a life-stage during which women undergo significant
      changes to their body and can feel acute responsibility for the development and
      well-being of the fetus. A synthesis of qualitative studies was conducted to
      increase our understanding of pregnancy experiences among women with an eating
      disorder. DESIGN: a systematic search of eight electronic databases was carried
      out to identify relevant investigations. Studies were appraised by two authors.
      Data were combined using framework analysis. From 459 references, seven papers
      were included in the review. FINDINGS: an overriding concept of inner turmoil
      transpired from the synthesis. This personal conflict related to the fear and
      guilt expressed by interviewees and stemmed from their association of self-worth
      with their body, concerns about their child's health and worries about others'
      response to their eating and weight control practices. KEY CONCLUSIONS:
      participants reported vacillating between wanting to do the best for their child,
      being motivated by social pressures and feeling the need to control their body
      for self-preservation purposes. This created the inner turmoil they experienced
      while pregnant. IMPLICATIONS FOR PRACTICE: midwives should be sensitive to the
      possibility of an eating disorder among pregnant women. In such cases,
      practitioners could act as a conduit for any assistance required, guiding these
      mothers towards appropriate nutritional and psychological support. To do this,
      professionals must have knowledge of such conditions and be aware of services
      available for women disclosing disordered eating behaviours.

PMID- 23149239
TI  - Women's perceptions of emotional support following childbirth: a qualitative
      investigation.
AB  - OBJECTIVE: to describe perceptions of participating in a study testing the
      effectiveness of a perinatal emotional support intervention (Promoting Resilience
      in Mothers Emotions; PRIME) by women identified as experiencing emotional
      distress after birth. DESIGN: qualitative descriptive approach. Semi-structured
      telephone interviews with 33 women recruited as part of a larger RCT to test the
      efficacy of a counselling intervention (PRIME). Women who received either (1) the
      intervention (counselling (or PRIME)) (n=16), (2) active control (Parenting
      support) (n=12), or (3) matched control (standard care) (n=5), were interviewed
      at 12 months postpartum. Thematic analysis of data was used. FINDINGS: 'promoting
      reflection' and 'feeling cared for', were phrases that all participants used to
      describe their experience in the project regardless of group allocation. Women
      receiving PRIME reported 'getting in touch with (their) feelings' and 'moving on'
      as beneficial outcomes. Two women who received counselling reported 'having
      things left unresolved' indicating that their needs had not been met. Some women
      in both the active control and intervention identified that contact was 'nice but
      not hugely helpful or needed'. IMPLICATIONS AND CONCLUSIONS: positive outcomes of
      PRIME were evident and most participants desired postpartum contact. Some women
      needed additional follow up and targeted assistance. Findings support the
      importance of providing personalised postnatal care that addresses women's
      emotional health needs.

PMID- 23149240
TI  - 'Every pregnant woman needs a midwife'--the experiences of HIV affected women in
      maternity care.
AB  - TITLE: 'Every pregnant woman needs a midwife'-the experiences of HIV affected
      women in Northern Ireland. OBJECTIVE: to explore HIV positive women's experiences
      of pregnancy and maternity care, with a focus on their interactions with
      midwives. DESIGN: a prospective qualitative study. SETTING: regional HIV unit in
      Northern Ireland. PARTICIPANTS: 22 interviews were conducted with 10 women at
      different stages of their reproductive trajectories. FINDINGS: the pervasive
      presence of HIV related stigma threatened the women's experience of pregnancy and
      care. The key staff attributes that facilitated a positive experience were
      knowledge and experience, empathy and understanding of their unique needs and
      continuity of care. KEY CONCLUSIONS: pregnancy in the context of HIV, whilst
      offering a much needed sense of normality, also increases woman's sense of
      anxiety and vulnerability and therefore the need for supportive interventions
      that affirm normality is intensified. A maternity team approach, with a focus on
      providing 'balanced care' could meet all of the woman and child's medical needs,
      whilst also emphasising the normalcy of pregnancy.

PMID- 23149241
TI  - Removable partial denture with molar uprighting spring: an innovative hybrid
      appliance.
AB  - PATIENT: A 45-year-old female patient with need of fixed replacement of her
      missing teeth which were lost long time before. Posterior teeth were severally
      tipped bilaterally in the edentulous space. Hybrid removable partial denture with
      molar uprighting spring was fabricated for molar uprighting on both side tilted
      molars. After 3 month and 15 days of treatment with hybrid appliance the molar
      abutment were uprighted for fabrication of fixed partial dentures. DISCUSSION:
      The objective in molar uprighting is ideal positioning of the molar which will
      eventually become an abutment tooth for a fixed prosthesis. The ideal position
      will provide an optimal periodontal environment for the molar. The prosthodontic
      advantages of molar uprighting via distal tipping include an improved line-of
      draw if a FPD is being constructed. Concept of designing of appliances was based
      on our basic knowledge of forces for uprighting the tooth along with maintaining
      the function during the treatment period. Another advantage of this appliance was
      that it prevented supra eruption of opposing teeth during the period when the
      molar was being uprighted. CONCLUSION: Uprighting of tilted molar is extremely
      beneficial for long term success of fixed denture prosthesis by using hybrid
      appliances in very short period of treatment without hampering the function of
      the patient during the treatment period which is very economical as well.

PMID- 23149242
TI  - Adaptive Resonance Theory: how a brain learns to consciously attend, learn, and
      recognize a changing world.
AB  - Adaptive Resonance Theory, or ART, is a cognitive and neural theory of how the
      brain autonomously learns to categorize, recognize, and predict objects and
      events in a changing world. This article reviews classical and recent
      developments of ART, and provides a synthesis of concepts, principles,
      mechanisms, architectures, and the interdisciplinary data bases that they have
      helped to explain and predict. The review illustrates that ART is currently the
      most highly developed cognitive and neural theory available, with the broadest
      explanatory and predictive range. Central to ART's predictive power is its
      ability to carry out fast, incremental, and stable unsupervised and supervised
      learning in response to a changing world. ART specifies mechanistic links between
      processes of consciousness, learning, expectation, attention, resonance, and
      synchrony during both unsupervised and supervised learning. ART provides
      functional and mechanistic explanations of such diverse topics as laminar
      cortical circuitry; invariant object and scenic gist learning and recognition;
      prototype, surface, and boundary attention; gamma and beta oscillations; learning
      of entorhinal grid cells and hippocampal place cells; computation of homologous
      spatial and temporal mechanisms in the entorhinal-hippocampal system; vigilance
      breakdowns during autism and medial temporal amnesia; cognitive-emotional
      interactions that focus attention on valued objects in an adaptively timed way;
      item-order-rank working memories and learned list chunks for the planning and
      control of sequences of linguistic, spatial, and motor information; conscious
      speech percepts that are influenced by future context; auditory streaming in
      noise during source segregation; and speaker normalization. Brain regions that
      are functionally described include visual and auditory neocortex; specific and
      nonspecific thalamic nuclei; inferotemporal, parietal, prefrontal, entorhinal,
      hippocampal, parahippocampal, perirhinal, and motor cortices; frontal eye fields;
      supplementary eye fields; amygdala; basal ganglia: cerebellum; and superior
      colliculus. Due to the complementary organization of the brain, ART does not
      describe many spatial and motor behaviors whose matching and learning laws differ
      from those of ART. ART algorithms for engineering and technology are listed, as
      are comparisons with other types of models.

PMID- 23149244
TI  - Urinary bisphenol A concentrations in pregnant women.
AB  - Bisphenol A is a chemical that is present in a number of products and types of
      food packaging. Prenatal exposure to bisphenol A may cause behavioural changes in
      young children. The aim of this study was to investigate exposure to bisphenol A
      in pregnant Australian women as a surrogate of neonatal exposure. First morning
      void urine samples were collected from 26 pregnant women at around week 38 of
      gestation. Bisphenol A was detectable in 85% of the samples analysed. The median
      concentration in this group of women was 2.41MUg/L with a range of <LOD -
      5.66MUg/L. Women experiencing their first pregnancy had slightly higher urinary
      bisphenol A concentrations, as did women with a pre-pregnancy BMI of <25, however
      these relationships did not reach significance. This study provides the first
      information on bisphenol A exposure in Australia and reveals that pregnant women
      have measured biological concentrations of urinary bisphenol A similar to those
      reported for pregnant women in other developed countries. Given the potential
      impacts of prenatal bisphenol A exposure, further research in this area is
      warranted. 

PMID- 23149243
TI  - Recanalization of occluded large arteries with broadened therapeutic window for
      acute cerebral infarction.
AB  - OBJECTIVE: To investigate the safety and efficacy of recanalization with a
      broadened therapeutic window for acute occlusion of large cerebral arteries.
      METHODS: We assessed 38 patients who underwent the hyper-selective intra-arterial
      administration of low-dose urokinase, along with mechanical thrombus disruption
      or mechanical thrombus disruption recanalization (34 stents in 33 patients) of
      occluded vessels, 20 with onset time-to-treatment (OTT) >6 h (observation group;
      mean OTT, 20.10+/-15.67 h) and 18 with OTT <=6 h (control group). NIHSS scores,
      mRS scores (<=2) at 3 months, recanalization rates, severe cerebral infarctions
      on CT, and symptomatic hemorrhagic conversions after surgery were compared.
      RESULTS: Postoperative recanalization rates were 100% in both groups, and other
      results were equivalent. CONCLUSIONS: Recanalization at longer OTT was safe and
      effective with acute occlusions of large cerebral arteries. Time to
      recanalization could be safely prolonged for up to 20 h in these patients.

PMID- 23149245
TI  - Mitochondrial and nuclear sequence polymorphisms reveal geographic structuring in
      Amazonian populations of Echinococcus vogeli (Cestoda: Taeniidae).
AB  - To date, nothing is known about the genetic diversity of the Echinococcus
      neotropical species, Echinococcus vogeli and Echinococcus oligarthrus. Here we
      used mitochondrial and nuclear DNA sequence polymorphisms to uncover the genetic
      structure, transmission and history of E. vogeli in the Brazilian Amazon, based
      on a sample of 38 isolates obtained from human and wild animal hosts. We confirm
      that the parasite is partially synanthropic and show that its populations are
      diverse. Furthermore, significant geographical structuring is found, with western
      and eastern populations being genetically divergent.

PMID- 23149246
TI  - Ageing towards 21 as a risk factor for Young Adult Suicide in the UK and Ireland.
AB  - Aims. Youth and young adult suicide has increasingly appeared on international
      vital statistics as a rising trend of concern in age-specific mortality over the
      past 50 years. The reporting of suicide deaths in 5-year age bands, which has
      been the international convention to date, may mask a greater understanding of
      year-on-year factors that may accelerate or ameliorate the emergence of suicidal
      thoughts, acts and fatal consequences. The study objective was to identify any
      year-on-year period of increased risk for youth and young adult suicide in the UK
      and Ireland. Methods. Collation and examination of international epidemiological
      datasets on suicide (aged 18-35) for the UK and Ireland 2000-2006 (N = 11 964).
      Outcome measures included the age distribution of suicide mortality in
      international datasets from the UK and Ireland, 2000-2006. Results. An
      accelerated pattern of risk up to the age of 20 for the UK and Ireland which
      levels off moderately thereafter was uncovered, thus identifying a heretofore
      unreported age-related epidemiological transition for suicide. Conclusions. The
      current reporting of suicide in 5-year age bands may conceal age-related periods
      of risk for suicide. This may have implications for suicide prevention programmes
      for young adults under age 21. 

PMID- 23149247
TI  - Sudden cardiac arrest in ESRD patients.
AB  - End-stage renal disease (ESRD) carries a significant risk for sudden cardiac
      arrest (SCA), hospitalization and mortality. We present a case of a vintage
      hemodialysis patient who had a catastrophic event during his hemodialysis
      treatment - a sudden cardiac arrest. This case raises several important issues:
      First, patients with chronic kidney disease (CKD) (and particularly ESRD) are
      predisposed to an inordinate risk of SCA; second, the factors leading to SCA in
      CKD are unique; and lastly, it is of paramount importance to have basic life
      support training, crash carts and defibrillators in dialysis units. It also
      raises the important discussion regarding the role for automated implantable
      cardioverter defibrillators and medical therapy for the prevention of SCA in this
      population. 

PMID- 23149248
TI  - Interaction of malnutrition, N-terminal pro-B-type natriuretic peptide and
      ventricular remodeling in patients on maintenance hemodialysis.
AB  - AIMS: The aim of the present study was to investigate the interaction of
      nutritional status, N-terminal probrain-type natriuretic peptide (NT-proBNP) and
      ventricular remodeling in hemodialysis patients. METHODS: NT-proBNP was measured
      by immunoassay. Nutritional status was assessed using the subjective global
      assessment (SGA) and malnutrition-inflammation score (MIS). Transthoracic
      echocardiographic examinations were performed on all patients. RESULTS: 44
      patients undergoing maintenance hemodialysis were enrolled in this study.
      Malnourished patients had higher levels of extracellular water (ECW) per kg body
      weight (BWt) than well-nourished patients and higher levels of NT-proBNP. MIS was
      positively correlated with left ventricular mass index (LVMI), log NT-proBNP and
      ECW/BWt, and negatively correlated with fat mass and LV systolic dysfunction. LV
      systolic dysfunction, LVMI and MIS were independently associated with log NT
      proBNP levels. Multiple regression analysis showed that log NT-proBNP, mean
      arterial pressure and ECW/BWt were independently associated with LVMI. However,
      MIS did not have an independent relationship to LVMI. CONCLUSIONS: Malnutrition
      in hemodialysis patients is accompanied by volume overload and associated with
      increased log NT-proBNP levels independent of volume status, and these levels are
      independently associated with increased LVMI. This suggests a possibility that
      nutritional status may affect ventricular remodeling in hemodialysis patients.

PMID- 23149249
TI  - Membranoproliferative glomerulonephritis Type 3 associated with Kabuki syndrome.
AB  - First described in Japanese patients, Kabuki syndrome (KS) is a congenital
      condition associated with multiple anomalies and mental retardation. Although
      urological and immune abnormalities are common in KS, immune complex nephritis
      such as membranoproliferative glomerulonephritis (MPGN) has not yet been
      reported. We describe the first reported case of a KS patient with common
      variable immunodeficiency (CVI) and recurrent otitis media who developed severe
      proteinuria and hematuria due to MPGN Type 3 detected during the school urinary
      screening program in Japan. The patient was intravenously treated with
      methylprednisolone pulses followed by alternate-day prednisolone and an
      angiotensin receptor blocker. The patient showed remarkable improvement in both
      histological and urinary analyses. This case report suggests that immune
      abnormalities associated with KS can play an important role in the development of
      MPGN. Urinalysis should be regularly performed in KS patients with
      hypogammaglobulinemia and/or recurrent infection. 

PMID- 23149250
TI  - Rapidly progressive glomerulonephritis due to anti-glomerular basement membrane
      disease accompanied by IgA nephropathy: a case report.
AB  - Anti-glomerular basement membrane (anti-GBM) disease is characterized by
      autoantibodies against antigenic site on type IV collagen of the GBM. The
      coexistence of anti-GBM disease and other immune complex mediated
      glomerulonephritis is common. Herein, we describe a patient presented with
      rapidly progressive glomerulonephritis, who was diagnosed as IgA-mediated
      nephropathy and was found to have abundant serum anti-glomerular basement
      membrane IgG antibodies. The patient's renal function improved considerably with
      intensive immunosuppressive therapy. 

PMID- 23149251
TI  - Chaga mushroom-induced oxalate nephropathy.
AB  - Chaga mushrooms have been used in folk and botanical medicine as a remedy for
      cancer, gastritis, ulcers, and tuberculosis of the bones. A 72-year-old Japanese
      female had been diagnosed with liver cancer 1 year prior to presenting at our
      department. She underwent hepatectomy of the left lobe 3 months later. Chaga
      mushroom powder (4 - 5 teaspoons per day) had been ingested for the past 6 months
      for liver cancer. Renal function decreased and hemodialysis was initiated. Renal
      biopsy specimens showed diffuse tubular atrophy and interstitial fibrosis.
      Oxalate crystals were detected in the tubular lumina and urinary sediment and
      oxalate nephropathy was diagnosed. Chaga mushrooms contain extremely high oxalate
      concentrations. This is the first report of a case of oxalate nephropathy
      associated with ingestion of Chaga mushrooms. 

PMID- 23149252
TI  - Magnetic field activated lipid-polymer hybrid nanoparticles for stimuli
      responsive drug release.
AB  - Stimuli-responsive nanoparticles (SRNPs) offer the potential of enhancing the
      therapeutic efficacy and minimizing the side-effects of chemotherapeutics by
      controllably releasing the encapsulated drug at the target site. Currently
      controlled drug release through external activation remains a major challenge
      during the delivery of therapeutic agents. Here we report a lipid-polymer hybrid
      nanoparticle system containing magnetic beads for stimuli-responsive drug release
      using a remote radio frequency (RF) magnetic field. These hybrid nanoparticles
      show long-term stability in terms of particle size and polydispersity index in
      phosphate-buffered saline (PBS). Controllable loading of camptothecin (CPT) and
      Fe(3)O(4) in the hybrid nanoparticles was demonstrated. RF-controlled drug
      release from these nanoparticles was observed. In addition, cellular uptake of
      the SRNPs into MT2 mouse breast cancer cells was examined. Using CPT as a model
      anticancer drug the nanoparticles showed a significant reduction in MT2 mouse
      breast cancer cell growth in vitro in the presence of a remote RF field. The ease
      of preparation, stability, and controllable drug release are the strengths of the
      platform and provide the opportunity to improve cancer chemotherapy.

PMID- 23149253
TI  - Mechanical properties and structure of the biological multilayered material
      system, Atractosteus spatula scales.
AB  - During recent decades, research on biological systems such as abalone shell and
      fish armor has revealed that these biological systems employ carefully arranged
      hierarchical multilayered structures to achieve properties of high strength, high
      ductility and light weight. Knowledge of such structures may enable pathways to
      design bio-inspired materials for various applications. This study was conducted
      to investigate the spatial distribution of structure, chemical composition and
      mechanical properties in mineralized fish scales of the species Atractosteus
      spatula. Microindentation tests were conducted, and cracking patterns and damage
      sites in the scales were examined to investigate the underlying protective
      mechanisms of fish scales under impact and penetration loads. A difference in
      nanomechanical properties was observed, with a thinner, stiffer and harder outer
      layer (indentation modulus ~69 GPa and hardness ~3.3 GPa) on a more compliant and
      thicker inner layer (indentation modulus ~14.3 GPa and hardness ~0.5 GPa). High
      resolution scanning electron microscopy imaging of a fracture surface revealed
      that the outer layer contained oriented nanorods embedded in a matrix, and that
      the nanostructure of the inner layer contained fiber-like structures organized in
      a complex layered pattern. Damage patterns formed during microindentation show
      complex deformation mechanisms. Images of cracks identify growth through the
      outer layer, then deflection along the interface before growing and arresting in
      the inner layer. High-magnification images of the crack tip in the inner layer
      show void-linking and fiber-bridging exhibiting inelastic behavior. The observed
      difference in mechanical properties and unique nanostructures of different layers
      may have contributed to the resistance of fish scales to failure by impact and
      penetration loading.

PMID- 23149254
TI  - Provision of cardiopulmonary resuscitation differs across ethnic and racial
      groups.

PMID- 23149255
TI  - Design, synthesis, and evaluation of (E)-N-substituted benzylidene-aniline
      derivatives as tyrosinase inhibitors.
AB  - We attempted to design and synthesize (E)-N-substituted benzylidene-hydroxy or
      methoxy-aniline derivatives and to evaluate their inhibitory effect on tyrosinase
      activity and anti-melanogenesis activity in murine B16F10 melanoma cells.
      Derivatives with a 4-methoxy- or 4-hydroxy-anilino group exerted more potent
      inhibition against mushroom tyrosinase than those with a 2-hydroxyanilino group.
      (E)-4-((4-Hydroxyphenylimino)methyl)benzene-1,2-diol exhibited the most potent
      and non-competitive inhibition on mushroom tyrosinase showing an IC(50) of 17.22
      +/- 0.38 MUM and being more effective than kojic acid (51.11 +/- 1.42 MUM). This
      compound decreased melanin production stimulated by the alpha-melanocyte
      stimulating hormone and inhibited murine tyrosinase activity in a dose-dependent
      manner. Therefore, we propose (E)-4-((4-hydroxyphenylimino)methyl)benzene-1,2
      diol as a new candidate of potent tyrosinase inhibitors that could be used as
      therapeutic agent with safe skin-whitening efficiency.

PMID- 23149256
TI  - Synthesis of novel pyrrolyl-indomethacin derivatives.
AB  - In the present work, we report the synthesis of the novel esters of indomethacin
      (IDMC) and an ester of reduced IDMC. For this purpose, IDMC is covalently bound
      by using a spacer chain to the pyrrole (Py) in the 3-position. The innovative
      pyrrole-indomethacin (3-Py-IDMC) derivates show no cytotoxic effects in primary
      calvarial osteoblasts. The designed IDMC derivates have been studied because they
      could be injected locally as a component of polymeric micro-particles. In fact,
      the new 3-Py-IDMC derivatives will assure their further polymerization since the
      2- and 5-monomer positions are free.

PMID- 23149257
TI  - Evaluation of combination therapy schedules of doxorubicin and an acid-sensitive
      albumin-binding prodrug of doxorubicin in the MIA PaCa-2 pancreatic xenograft
      model.
AB  - In this work, we evaluated combinations of doxorubicin with INNO-206, a (6
      maleimidocaproyl)hydrazone derivative of doxorubicin (DOXO-EMCH) that is
      currently undergoing two phase II clinical trials, in a primarily chemoresistant
      tumor indication, i.e. pancreatic cancer. Thus, we compared the antitumor
      efficacy and tolerability of the following weekly intravenous treatments in the
      MIA PaCa-2 xenograft model: 3*6 mg doxorubicin (MTD), 3*24 mg/kg DOXO-EMCH
      (doxorubicin equivalents, MTD), 3*3 mg/kg doxorubicin followed 6h later by 3*12
      mg/kg DOXO-EMCH, and 3*12 mg/kg DOXO-EMCH followed 6 h later by 3*3 mg/kg
      doxorubicin. Whereas therapy with doxorubicin only produced a moderate tumor
      inhibition, all other therapy arms induced complete and partial remissions up to
      the end of the experiment on day 43. Although the total amount of doxorubicin
      equivalents is 72 mg/kg when DOXO-EMCH is administered alone, but only 45 mg/kg
      doxorubicin equivalents are administered in the combination regimens, the
      antitumor efficacy in all treated groups was essentially identical, a surprising
      finding of this study. However, there were significant differences in the
      tolerability as assessed by the body weight changes: whereas therapy at the MTD
      of DOXO-EMCH (3*24 mg/kg) produced a body weight loss of -16% including one
      death, therapy with 3*12 mg/kg DOXO-EMCH followed 6h later by 3*3 mg/kg
      doxorubicin produced -7% body weight loss, and 3*3 mg/kg doxorubicin followed 6h
      later by 3*12 mg/kg DOXO-EMCH produced a body weight gain of +2% as a clear
      indication of minimal systemic toxicity. In addition, cell culture experiments
      revealed additive to synergistic effects when MIA PaCa-2 cells were exposed to
      doxorubicin followed 6h later to exposure of the albumin-bound form of DOXO-EMCH
      spanning a ratio of 1:5 to 5:1 (analyzed for synergistic, additive or
      antagonistic effects using the software program CalcuSyn((r))). This animal study
      demonstrates that the time-dependent schedule of an albumin-binding prodrug and a
      free drug has a critical influence on the overall tolerability. A combination of
      doxorubicin and DOXO-EMCH is currently being investigated in a phase Ib study.

PMID- 23149259
TI  - Cost-effectiveness of farm interventions for reducing the prevalence of VTEC O157
      on UK dairy farms.
AB  - A randomized control trial on verocytotoxigenic Escherichia coli (VTEC)-infected
      farms found evidence that: (1) keeping animals in the same group; (2) maintaining
      dry bedding; (3) preventing direct contact with neighbouring cattle; and (4)
      maintaining a closed herd, were associated with a reduced risk of infection in
      youngstock aged 3-18 months. This study evaluated these interventions using a
      cost-effectiveness framework for UK dairy farms. Keeping animals in the same
      group was considered to have negligible cost and was feasible for herds
      containing over 77 dairy cows. Assuming equal efficacy of the remaining
      interventions, preventing direct contact between neighbouring cattle is most cost
      effective with a median annual cost of L2.76 per cow. This compares to L4.18 for
      maintaining dry bedding and L17.42 for maintaining a closed herd using quarantine
      procedures. Further model validation and exploration of other potential benefits
      are required before making policy decisions on VTEC control.

PMID- 23149260
TI  - Cyprus health system review.
AB  - The health system in Cyprus comprises separate public and private systems of
      similar size. The public system, which is financed by the state budget, is highly
      centralized and tightly controlled by the Ministry of Health. Entitlement to
      receive free health services is based on residency and income level. The private
      system is almost completely separate from the public system and for the most part
      is unregulated and largely financed out of pocket. In many ways there is an
      imbalance between the public and private sectors. The public system suffers from
      long waiting lists for many services, a situation that has been worsened by the
      recent economic crisis, while the private sector has an overcapacity of expensive
      medical technology that is underutilized. To try to address these and other
      inefficiencies, a new national health insurance scheme funded by taxes and social
      insurance contributions has been designed to offer universal coverage and
      introduce competition between the public and private sectors through changes in
      provider payment methods. However, the scheme has not been implemented due to
      cost concerns. Despite the low share of economic resources dedicated to health
      care and access issues for some vulnerable population groups, overall Cypriots
      enjoy good health comparable to other high-income countries.

PMID- 23149258
TI  - Dexamethasone eye drops containing gamma-cyclodextrin-based nanogels.
AB  - Sustained release aqueous eye drops of dexamethasone, based on cyclodextrin (CD)
      nanogels, were designed and tested in vivo. gammaCD units were cross-linked in
      the form of nanogels by means of an emulsification/solvent evaporation process.
      The composition of the nanogels was optimized with regard to drug loading and
      release rate. The eye drops consisted of an aqueous solution of dexamethasone in
      2-hydroxypropyl-gamma-cyclodextrin (HPgammaCD) medium containing gammaCD
      nanogels. The nanogel eye drops (containing 25 mg dexamethasone per ml) were
      tested in rabbits and compared to the commercially available product Maxidex((r))
      (suspension with 1 mg dexamethasone per ml). One drop administration of the
      nanogel eye drops resulted in nearly constant dexamethasone concentration for at
      least 6h in the tear fluid (mean concentration+/-SD=295+/-59 MUg/ml) whereas the
      concentration after administration of Maxidex((r)) fell rapidly from 9.72+/-3.45
      MUg/ml 1 h after application to 3.76+/-3.26 MUg/ml 3 h after application. The
      maximum dexamethasone concentration in the aqueous humor (2 h after application)
      was 136+/-24 mg/ml after application of the nanogel eye drops, and only 44.4+/
      7.8 MUg/ml after application of Maxidex((r)). The dexamethasone nanogel eye drops
      were well tolerated with no macroscopic signs of irritation, redness or other
      toxic effects.

PMID- 23149262
TI  - Gastric band adjustment credentialing guidelines for physician extenders.

PMID- 23149264
TI  - Susac's syndrome: a case of simultaneous development of all three components of
      the triad.
AB  - Susac's syndrome is characterized by the clinical triad of encephalopathy, branch
      retinal artery occlusions and sensorineural hearing loss. We here report a case
      of 46 year old woman with a sudden diminution in visual acuity at the left eye,
      headache and decreased hearing at the right ear with mild confusion considered as
      Susac's syndrome with complete triad. Although it's a relatively rare entity, it
      should be kept in mind in differential diagnosis of the neurological disorders,
      especially in women in 20- to 40-year of age presenting with acute hearing loss.

PMID- 23149263
TI  - Myocardial structural associations with local electrograms: a study of
      postinfarct ventricular tachycardia pathophysiology and magnetic resonance-based
      noninvasive mapping.
AB  - BACKGROUND: The association of scar on late gadolinium enhancement cardiac
      magnetic resonance (LGE-CMR) with local electrograms on electroanatomic mapping
      has been investigated. We aimed to quantify these associations to gain insights
      regarding LGE-CMR image characteristics of tissues and critical sites that
      support postinfarct ventricular tachycardia (VT). METHODS AND RESULTS: LGE-CMR
      was performed in 23 patients with ischemic cardiomyopathy before VT ablation.
      Left ventricular wall thickness and postinfarct scar thickness were measured in
      each of 20 sectors per LGE-CMR short-axis plane. Electroanatomic mapping points
      were retrospectively registered to the corresponding LGE-CMR images.
      Multivariable regression analysis, clustered by patient, revealed significant
      associations among left ventricular wall thickness, postinfarct scar thickness,
      and intramural scar location on LGE-CMR, and local endocardial electrogram
      bipolar/unipolar voltage, duration, and deflections on electroanatomic mapping.
      Anteroposterior and septal/lateral scar localization was also associated with
      bipolar and unipolar voltage. Antiarrhythmic drug use was associated with
      electrogram duration. Critical sites of postinfarct VT were associated with >25%
      scar transmurality, and slow conduction sites with >40 ms stimulus-QRS time were
      associated with >75% scar transmurality. CONCLUSIONS: Critical sites for
      maintenance of postinfarct VT are confined to areas with >25% scar transmurality.
      Our data provide insights into the structural substrates for delayed conduction
      and VT and may reduce procedural time devoted to substrate mapping, overcome
      limitations of invasive mapping because of sampling density, and enhance magnetic
      resonance-based ablation by feature extraction from complex images.

PMID- 23149265
TI  - A clinical study of syndromes of idiopathic (genetic) generalized epilepsy.
AB  - OBJECTIVES: Epidemiologic data concerning idiopathic generalized epilepsies
      (IGEs) are scarce or often unreliable. In the current study, we specifically
      analyzed the syndromes of IGE based on their demographic, clinical, and EEG
      findings to determine if other than the seizure type(s) and age of onset, there
      are any other distinctive features to distinguish these syndromes of IGEs from
      one another. MATERIALS AND METHODS: In this retrospective study, all patients
      with a clinical diagnosis of IGE were recruited at the outpatient epilepsy clinic
      at Shiraz University of Medical Sciences, from 2008 to 2011. Demographic
      variables and relevant clinical and EEG variables were summarized descriptively.
      Statistical analyses were performed using Chi square and Fisher's exact tests.
      RESULTS: 2190 patients with epilepsy were registered at our epilepsy clinic and
      442 patients (20.2%) were diagnosed as having IGE. Age of seizure onset was 12 +/
      7 years. Juvenile myoclonic epilepsy was the most frequent syndrome, followed by
      epilepsy with generalized tonic-clonic seizures only and juvenile absence
      epilepsy. Epilepsy risk factors, physical examination, MRI and even EEG could not
      differentiate various syndromes of IGE. CONCLUSION: The key element in making the
      correct diagnosis of an IGE syndrome is obtaining a detailed clinical history.
      However, other than the seizure type(s) and age of onset, there are no any other
      distinctive features to distinguish these syndromes of IGEs from one another.
      Besides, sometimes these syndromes have overlapping features.

PMID- 23149266
TI  - Atypical chronic lymphocytic inflammation with pontocerebellar perivascular
      enhancement responsive to steroids (CLIPPERS), primary angiitis of the CNS
      mimicking CLIPPERS or overlap syndrome? A case report.
AB  - A novel type of encephalomyelitis was first described as chronic lymphocytic
      inflammation with pontine perivascular enhancement responsive to steroids
      (CLIPPERS) in 2010 and few additional patients were reported since then.
      Partially due to its unknown aetiology and a lack of pathognomonic features some
      have suggested that CLIPPERS may not represent a distinct disease, but rather a
      syndrome with different underlying aetiologies. Here we report a 49-year-old
      German female who presented with a number of clinical and paraclinical features
      described as typical for CLIPPERS, while additionally showing symptoms and
      findings compatible with primary angiitis of the CNS (PACNS). This case may
      establish a previously unnoted link between two poorly understood autoimmune
      conditions of the CNS.

PMID- 23149267
TI  - TAT-mediated gp96 transduction to APCs enhances gp96-induced antiviral and
      antitumor T cell responses.
AB  - The heat shock protein gp96 is an adjuvant that can elicit T cell responses
      against cancer and infectious diseases, via antigen presentation, in both rodent
      models and clinical trials. Its uptake and internalization into antigen
      presenting cells (APCs) is a critical step in gp96-mediated immune responses.
      This study examined strategies to improve the cell internalization and T cell
      activation of gp96. It was found that recombinant fusion with the cell
      penetrating peptide TAT (trans-activator of transcription) slightly decreased the
      aggregation level of gp96 and significantly increased its internalization into
      macrophages. Furthermore, immunization with the TAT-gp96 fusion dramatically
      enhanced gp96-mediated hepatitis B virus (HBV)-specific T cell responses and its
      antiviral efficiency in HBV transgenic mice compared to rgp96. In addition, the
      inclusion of TAT significantly improved the antitumor T cell immune response to a
      gp96 vaccine in the B16 melanoma model. These results provide evidence that the
      efficient transduction of gp96 into APCs can significantly enhance the outcome of
      gp96-based immunotherapy, and therefore provide a basis for more efficient
      approaches to improving the immunoregulatory and adjuvant functions of this
      unique T cell adjuvant.

PMID- 23149268
TI  - Global production capacity of seasonal influenza vaccine in 2011.
AB  - The effectiveness of vaccines to mitigate the impact of annual seasonal influenza
      epidemics and influenza pandemics has been well documented. However, the steady
      increase in global capacity to produce annual seasonal influenza vaccine has not
      been matched with increased demand, and thus actual vaccine production.
      Currently, without a significant increase in demand for seasonal influenza
      vaccine, global capacity will be far from able to meet even the essential needs
      for a monovalent vaccine in the event of a severe influenza pandemic. Global
      commitment to the development of influenza vaccine production capacity was
      renewed at a consultation leading to the Second Global Action Plan on Influenza
      Vaccines (GAP) in July 2011. To monitor progress on the GAP, the World Health
      Organization has carried out periodic surveys of influenza vaccine manufacturers.
      This latest survey compares current maximum global capacity and actual production
      of seasonal influenza vaccine in 2011 with data from surveys carried out in 2009
      and 2010; analyses global influenza production capacity in the context of
      sustainability; and discusses options to increase demand, based on strong
      evidence of public health benefit.

PMID- 23149269
TI  - Control of viral hepatitis infection in Africa: are we dreaming?
AB  - BACKGROUND: At least five different types of viral hepatitis cause problems of
      significant public health importance in Africa, where together they constitute a
      huge burden of disease. But until now, efforts to control the infections have
      been largely piecemeal. Analysis of the strategies needed to control each virus,
      however, reveals major overlaps. PROPOSAL: We propose that the control of these
      infections in the WHO African Region should start with the common strategies
      rather than with each disease. But this approach presents potentially huge
      problems to overcome, such as the difficulty of integrating multiple health
      service elements - the track record for successful integration of such services
      is not good. This is despite encouraging rhetoric from donors and national
      leaders alike. And to succeed, disparate programmes must work closely together.
      But we believe that the time is right to create new opportunities for prevention
      and treatment of hepatitis, including increasing education, and promoting
      screening and treatment for more than 500 million people already infected with
      hepatitis B and C viruses. IMPACT: The impact of these efforts on decreasing
      mortality and morbidity will be significant because of the high burden of disease
      from these infections, and also because the effect will spill over to benefit the
      control of other communicable diseases and health systems strengthening. Such a
      project will inevitably involve multiple strategies that will vary somewhat
      according to the epidemiology of the diseases and the location.

PMID- 23149270
TI  - Immunogenicity and protective efficacy of recombinant Haemophilus parasuis SH0165
      putative outer membrane proteins.
AB  - Haemophilus parasuis (H. parasuis), the causative agent of swine polyserositis,
      polyarthritis, and meningitis, is one of the most important bacterial diseases of
      pigs worldwide. Little vaccines currently exist that have a significant effect on
      infections with all pathogenic serovars of H. parasuis. H. parasuis putative
      outer membrane proteins (OMPs) are potentially essential components of more
      effective vaccines. Recently, the genomic sequence of H. parasuis serovar 5
      strain SH0165 was completed in our laboratory, which allow us to target OMPs for
      the development of recombinant vaccines. In this study, we focused on 10 putative
      OMPs and all the putative OMPs were cloned, expressed and purified as HIS fusion
      proteins. Primary screening for immunoprotective potential was performed in mice
      challenged with an LD50 challenge. Out of these 10 OMPs three fusion proteins
      rGAPDH, rOapA, and rHPS-0675 were found to be protective in a mouse model of H.
      parasuis infection. We further evaluated the immune responses and protective
      efficacy of rGAPDH, rOapA, and rHPS-0675 in pig models. All three proteins
      elicited humoral antibody responses and conferred different levels of protection
      against challenge with a lethal dose of H. parasuis SH0165 in pig models. In
      addition, the antisera against the three individual proteins and the synergistic
      protein efficiently inhibited bacterial growth in a whole blood assay. The data
      demonstrated that the three proteins showed high value individually and the
      combination of rGAPDH, rOapA, and rHPS-0675 offered the best protection. Our
      results indicate that rGAPDH, rOapA, and rHPS-0675 induced protection against H.
      parasuis SH0165 infection, which may facilitate the development of a multi
      component vaccine.

PMID- 23149272
TI  - Commentary on "Possible induction of acute disseminated encephalomyelitis (ADEM)
      like demyelinating illness by intrathecal mesenchymal stem cell injection".
AB  - The case report that is the subject of this Commentary describes a 27-year-old
      woman, who, 3 months after a devastating low cervical myelitis, underwent
      intrathecal mesenchymal stem cell (MSC) infusions. Six hours after the third
      infusion, she became unconscious, febrile and cerebral MRI showed acute
      bitemporal and left cerebellar lesions, consistent with an acute disseminated
      encephalomyelitis. It is likely that this is the first reported patient with
      neuroinflammatory exacerbation after MSC therapy. This case suggests that, in
      addition to their malignant potential, autologous MSC expanded in vitro can
      exhibit immune-activating properties leading to autoimmune exacerbation.

PMID- 23149271
TI  - Effects of a dynamic progressive orthotic intervention for chronic hemiplegia: a
      case series.
AB  - STUDY DESIGN: Case series design on a single subgroup of participants.
      INTRODUCTION: Management of hypertonicity and resistance to passive movement
      (RTPM) in the upper extremity is an intractable problem for persons with stroke
      and the therapists who provide their care. Therapists have limited options for
      assessment and treatment of this condition which can profoundly limit functional
      performance and quality of life. PURPOSE OF THE STUDY: To evaluate the effect of
      a 12-week dynamic progressive orthotic intervention in persons with chronic
      stroke exhibiting wrist flexion contracture who are residents of a long-term
      skilled nursing facility. METHODS: A custom-fitted dynamic progressive wrist
      extension orthotic was applied to 6 residents with chronic stroke. The orthotic
      was worn for 4 h daily, 4*/week for 12 weeks. Wrist passive range of motion
      (PROM) and RTPM were measured weekly and after discontinuation of the orthotics
      using the Modified Ashworth Scale and the Tardieu Scale of Spasticity. Signal
      analysis of electromyographical (EMG) flexor response to extensor stretching was
      also measured before and after orthotic intervention using maximal root mean
      square (RMS) values and EMG burst onset time. RESULTS: A moderate effect was
      found for changes in PROM with the orthotic intervention. Progress made
      diminished following discontinuation. Moderate effects were also seen in EMG
      measures which indicated increases in amount of resistive-free movement following
      intervention. CONCLUSION: A dynamic progressive orthotic intervention can be an
      effective option for increasing wrist PROM and reducing RTPM in persons with
      chronic stroke. LEVEL OF EVIDENCE: 4.

PMID- 23149273
TI  - Structural basis of the binding of fatty acids to peptidoglycan recognition
      protein, PGRP-S through second binding site.
AB  - Short peptidoglycan recognition protein (PGRP-S) is a member of the mammalian
      innate immune system. PGRP-S from Camelus dromedarius (CPGRP-S) has been shown to
      bind to lipopolysaccharide (LPS), lipoteichoic acid (LTA) and peptidoglycan
      (PGN). Its structure consists of four molecules A, B, C and D with ligand binding
      clefts situated at A-B and C-D contacts. It has been shown that LPS, LTA and PGN
      bind to CPGRP-S at C-D contact. The cleft at the A-B contact indicated features
      that suggested a possible binding of fatty acids including mycolic acid of
      Mycobacterium tuberculosis. Therefore, binding studies of CPGRP-S were carried
      out with fatty acids, butyric acid, lauric acid, myristic acid, stearic acid and
      mycolic acid which showed affinities in the range of 10(-5) to 10(-8) M.
      Structure determinations of the complexes of CPGRP-S with above fatty acids
      showed that they bound to CPGRP-S in the cleft at the A-B contact. The flow
      cytometric studies showed that mycolic acid induced the production of pro
      inflammatory cytokines, TNF-alpha and IFN-gamma by CD3+ T cells. The
      concentrations of cytokines increased considerably with increasing concentrations
      of mycolic acid. However, their levels decreased substantially on adding CPGRP-S.

PMID- 23149274
TI  - The breath of life - womens' experiences of breathing adapted radiation therapy.
AB  - PURPOSE: To describe and analyze how women with breast cancer experience
      breathing adapted radiation therapy (BART) and to explore how women manage daily
      radiation therapy. METHOD: Individual interviews were conducted with 20 women
      treated with BART for breast cancer concerning their perception of radiation
      therapy. The transcribed interviews were analyzed using qualitative content
      analysis. RESULTS: 'The breath of life' was the overall theme, as the women
      experienced the breathing as a way in which to influence their treatment and thus
      their survival. 'Participating in one's treatment, for good or ill', was the main
      category with four subcategories, 'Knowing one has done something good', 'Getting
      an extra bonus - healthwise', 'The experience of being in control' and 'Being in
      a high-technology environment'. The breathing technique became the strategy by
      which they could manage their treatment and gave them a sense of participation
      which led to a feeling of being in control. The women also felt that breathing
      benefited their health both mentally and physically. The high-technology
      environment was experienced as both hopeful and frightening. CONCLUSION: Survival
      or increasing the chances of survival, are of ultimate importance for a woman
      with breast cancer. BART requires commitment from the women, which was perceived
      as offering them an opportunity to participate in their own treatment, for their
      survival. Increasing the women's possibilities to participate in their treatment
      benefits their health and welfare during an otherwise turbulent time and allow
      the rehabilitation process to start during treatment.

PMID- 23149276
TI  - Resurfacing humeral prosthesis: do we really reconstruct the anatomy?
AB  - BACKGROUND: The goal of a resurfacing shoulder arthroplasty is to reproduce the
      individual's anatomy while preserving the bone stock of the humeral head. This
      study investigated the hypothesis that resurfacing the humeral prosthesis
      restores normal glenohumeral relationships and correlates with the final clinical
      results. MATERIALS AND METHODS: A resurfacing shoulder implant was performed in
      61 patients (64 shoulders). Indications were primary osteoarthritis in 26,
      secondary osteoarthritis in 21, avascular necrosis in 4, rheumatoid arthritis in
      4, dysplasia in 4, and for others indications in 5. RESULTS: At an average of 36
      months (range, 24-65) of follow-up , the Constant score reached 68 points and the
      Quick-Disabilities of Arm, Shoulder and Hand score reached 28 points.
      Preoperative and postoperative radiographic analysis showed a decrease of the
      humeral head diameter (51 +/- 5 vs 48 +/- 5 mm) and of the height of the humeral
      head (21 +/- 4 vs 19 +/- 2 mm), without modification of the radius of curvature
      or the height of the center of rotation. The medial humeral offset increased from
      3.3 +/- 3.5 to 6.4 +/- 3 mm and the lateral offset from 6.8 +/- 9 to 10.4 +/- 9
      mm. The implant was mainly in varus postoperatively compared with preoperative
      values (122 degrees  +/- 11 degrees  vs 134 degrees  +/- 7 degrees ).
      Postoperative radiographic analysis and at the last follow-up did not show any
      significant difference, except for the increase of the depth of the glenoid from
      4.2 +/- 1.4 to 4.9 +/- 1.8 mm. CONCLUSIONS: The resurfacing shoulder arthroplasty
      reproduces the normal anatomy and compensates glenohumeral wear. However, there
      was a tendency to position the prosthesis in varus because of technical
      imperfections. With follow-up, medialization of the humerus with glenoid wear was
      observed and was correlated in some patients with reappearance of pain.

PMID- 23149275
TI  - The Near-Road Exposures and Effects of Urban Air Pollutants Study (NEXUS): study
      design and methods.
AB  - The Near-Road Exposures and Effects of Urban Air Pollutants Study (NEXUS) was
      designed to examine the relationship between near-roadway exposures to air
      pollutants and respiratory outcomes in a cohort of asthmatic children who live
      close to major roadways in Detroit, Michigan USA. From September 2010 to December
      2012 a total of 139 children with asthma, ages 6-14, were enrolled in the study
      on the basis of the proximity of their home to major roadways that carried
      different amounts of diesel traffic. The goal of the study was to investigate the
      effects of traffic-associated exposures on adverse respiratory outcomes,
      biomolecular markers of inflammatory and oxidative stress, and how these
      exposures affect the frequency and severity of respiratory viral infections in a
      cohort of children with asthma. An integrated measurement and modeling approach
      was used to quantitatively estimate the contribution of traffic sources to near
      roadway air pollution and evaluate predictive models for assessing the impact of
      near-roadway pollution on children's exposures. Two intensive field campaigns
      were conducted in Fall 2010 and Spring 2011 to measure a suite of air pollutants
      including PM2.5 mass and composition, oxides of nitrogen (NO and NO2), carbon
      monoxide, and black carbon indoors and outdoors of 25 participants' homes, at two
      area schools, and along a spatial transect adjacent to I-96, a major highway in
      Detroit. These data were used to evaluate and refine models to estimate air
      quality and exposures for each child on a daily basis for the health analyses.
      The study design and methods are described, and selected measurement results from
      the Fall 2010 field intensive are presented to illustrate the design and
      successful implementation of the study. These data provide evidence of roadway
      impacts and exposure variability between study participants that will be further
      explored for associations with the health measures.

PMID- 23149277
TI  - High resolution quantitative computed tomography-based assessment of trabecular
      microstructure and strength estimates by finite-element analysis of the spine,
      but not DXA, reflects vertebral fracture status in men with glucocorticoid
      induced osteoporosis.
AB  - High-resolution quantitative computed tomography (HRQCT)-based analysis of spinal
      bone density and microstructure, finite element analysis (FEA), and DXA were used
      to investigate the vertebral bone status of men with glucocorticoid-induced
      osteoporosis (GIO). DXA of L1-L3 and total hip, QCT of L1-L3, and HRQCT of T12
      were available for 73 men (54.6+/-14.0years) with GIO. Prevalent vertebral
      fracture status was evaluated on radiographs using a semi-quantitative (SQ) score
      (normal=0 to severe fracture=3), and the spinal deformity index (SDI) score (sum
      of SQ scores of T4 to L4 vertebrae). Thirty-one (42.4%) subjects had prevalent
      vertebral fractures. Cortical BMD (Ct.BMD) and thickness (Ct.Th), trabecular BMD
      (Tb.BMD), apparent trabecular bone volume fraction (app.BV/TV), and apparent
      trabecular separation (app.Tb.Sp) were analyzed by HRQCT. Stiffness and strength
      of T12 were computed by HRQCT-based nonlinear FEA for axial compression, anterior
      bending and axial torsion. In logistic regressions adjusted for age,
      glucocorticoid dose and osteoporosis treatment, Tb.BMD was most closely
      associated with vertebral fracture status (standardized odds ratio [sOR]: Tb.BMD
      T12: 4.05 [95% CI: 1.8-9.0], Tb.BMD L1-L3: 3.95 [1.8-8.9]). Strength divided by
      cross-sectional area for axial compression showed the most significant
      association with spine fracture status among FEA variables (2.56 [1.29-5.07]).
      SDI was best predicted by a microstructural model using Ct.Th and app.Tb.Sp
      (r(2)=0.57, p<0.001). Spinal or hip DXA measurements did not show significant
      associations with fracture status or severity. In this cross-sectional study of
      males with GIO, QCT, HRQCT-based measurements and FEA variables were superior to
      DXA in discriminating between patients of differing prevalent vertebral fracture
      status. A microstructural model combining aspects of cortical and trabecular bone
      reflected fracture severity most accurately.

PMID- 23149278
TI  - Roles of Wnt/beta-catenin signalling pathway in the bony repair of injured growth
      plate cartilage in young rats.
AB  - Growth plate cartilage is responsible for longitudinal growth of the long bone in
      children, and its injury is often repaired by bony tissue, which can cause limb
      length discrepancy and/or bone angulation deformities. Whilst earlier studies
      with a rat growth plate injury repair model have identified inflammatory,
      mesenchymal infiltration, osteogenesis and remodeling responses, the molecular
      mechanisms involved in the bony repair remain unknown. Since our recent
      microarray study has strongly suggested involvement of Wnt-beta-catenin
      signalling pathway in regulating the growth plate repair and the pathway is known
      to play a crucial role in the osteogenic differentiation of mesenchymal
      progenitor cells, the current study investigated the potential roles of Wnt-beta
      catenin signalling pathway in the bony repair of injured tibial growth plate in
      rats. Immunohistochemical analysis of the growth plate injury site revealed beta
      catenin immunopositive cells within the growth plate injury site. Treatment of
      the injured rats with the beta-catenin inhibitor ICG-001 (oral gavage at
      200mg/kg/day for 8days, commenced at day 2 post injury) enhanced COL2A1 gene
      expression (by qRT-PCR) and increased proportion of cartilage tissue (by
      histological analysis), but decreased level of osterix expression and amount of
      bone tissue, at the injury site by day 10 post-injury (n=8, P<0.01 compared to
      vehicle controls). Consistently, in vitro studies with bone marrow stromal cells
      from normal rats showed that beta-catenin inhibitor ICG-001 dose dependently
      inhibited expression of Wnt target genes Cyclin D1 and survivin (P<0.01). At
      25mM, ICG-001 suppressed osteogenic (by CFU-f-ALP assay) but enhanced
      chondrogenic (by pellet culture) differentiation. These results suggest that
      Wnt/beta-catenin signalling pathway is involved in regulating growth plate injury
      repair by promoting osteoblastogenesis, and that intervention of this signalling
      could represent a potential approach in enhancing cartilage repair after growth
      plate injury.

PMID- 23149279
TI  - Prevalence inflation.

PMID- 23149280
TI  - Mental illness and mental health: is the glass half empty or half full?
AB  - During the past century, the scope of mental health intervention in North America
      has gradually expanded from an initial focus on hospitalized patients with
      psychoses to outpatients with neurotic disorders, including the so-called worried
      well. The Diagnostic and Statistical Manual of Mental Disorders (DSM), Fifth
      Edition, is further embracing the concept of a mental illness spectrum, such that
      increasing attention to the softer end of the continuum can be expected in the
      future. This anticipated shift rekindles important questions about how mental
      illness is defined, how to distinguish between mental disorders and normal
      reactions, whether psychiatry is guilty of prevalence inflation, and when somatic
      therapies should be used to treat problems of living. Such debates are aptly
      illustrated by the example of complicated bereavement, which is best
      characterized as a form of adjustment disorder. Achieving an overarching
      definition of mental illness is challenging, owing to the many different contexts
      in which DSM diagnoses are used. Careful analyses of such contextual utility must
      inform future decisions about what ends up in DSM, as well as how mental illness
      is defined by public health policy and society at large. A viable vision for the
      future of psychiatry should include a spectrum model of mental health (as opposed
      to exclusively mental illness) that incorporates graded, evidence-based
      interventions delivered by a range of providers at each point along its
      continuum.

PMID- 23149281
TI  - Bipolar disorder: the shift to overdiagnosis.
AB  - Sometimes dramatically changing vogues in diagnostic practice in psychiatry
      resemble the volatility of international share markets. One such quickly shifting
      diagnostic area has been that of bipolar disorder (BD). Historically regarded as
      a relatively uncommon condition until recent decades, the construct of BD
      underwent a major expansion in the 1990s and 2000s with promulgation of the
      concept of the soft bipolar spectrum disorder, from which the recent research
      focus on subthreshold BD presentations was derived. Related to this has been
      renewed interest in treatments for BD from the pharmaceutical industry. The
      increasing rates of diagnosis have largely related to BD II, for which there has
      been a dramatic broadening of diagnostic criteria. This article critically
      reviews research data, both for broadening the diagnostic criteria for BD and,
      conversely, for the growing evidence of overdiagnosis in clinical practice. Why
      does this debate matter? I would suggest that there are many valid reasons to be
      concerned about overdiagnosis: first, the potential for overtreatment or
      inappropriate treatment of such patients with mood stabilizing treatments,
      including antipsychotics; second, the potential for diagnostic
      oversimplification, with consequent diagnostic deskilling and loss of credibility
      for the psychiatric profession; and third, the potential major impact on
      etiologic research for this condition. Psychiatry should not uncritically accept
      the shift to overdiagnosis, which has developed a rapid momentum in recent
      decades, in both clinical and academic circles. We must ensure, as a profession,
      that any change in diagnostic practice is underpinned by rigorous and critical
      research inquiry.

PMID- 23149282
TI  - Predictors of psychiatric aftercare among formerly hospitalized adolescents.
AB  - OBJECTIVE: Timely aftercare can be viewed as a patient safety imperative. In the
      context of decreasing inpatient length of stay (LOS) and known child psychiatry
      human resource challenges, we investigated time to aftercare for adolescents
      following psychiatric hospitalization. METHOD: We conducted a population-based
      cohort study of adolescents aged 15 to 19 years with psychiatric discharge
      between April 1, 2002, and March 1, 2004, in Ontario, using encrypted identifiers
      across health administrative databases to determine time to first psychiatric
      aftercare with a primary care physician (PCP) or a psychiatrist within 395 days
      of discharge. RESULTS: Among the 7111 adolescents discharged in the study period,
      24% had aftercare with a PCP or a psychiatrist within 7 days and 49% within 30
      days. High socioeconomic status (adjusted hazard ratio [AHR] 1.31; 95% CI 1.21 to
      1.43, P < 0.001) and psychotic disorders (AHR 1.24; 95% CI 1.12 to 1.36, P <
      0.001) were associated with greater likelihood of aftercare. Youth in the
      northern part of the province (AHR 0.48; 95% CI 0.32 to 0.71, P < 0.001), rural
      areas (AHR 0.82; 95% CI 0.76 to 0.89, P < 0.001), and with self-harm or suicide
      attempts (AHR 0.58; 95% CI 0.53 to 0.64, P < 0.001) and substance use disorders
      (AHR 0.50; 95% CI 0.44 to 0.56, P < 0.001) were less likely to receive aftercare.
      CONCLUSIONS: Hospitalization is our most intensive, intrusive, and expensive
      psychiatric treatment setting, yet in our cohort of formerly hospitalized
      adolescents fewer than 50% received psychiatry-related aftercare in the month
      postdischarge. Innovations are necessary to address geographic inequities and
      improve timely access to mental health aftercare for all youth.

PMID- 23149283
TI  - Childhood maltreatment and substance use disorders among men and women in a
      nationally representative sample.
AB  - OBJECTIVE: To examine the association between a history of 5 types of childhood
      maltreatment (that is, physical abuse, sexual abuse, emotional abuse, physical
      neglect, and emotional neglect) and several substance use disorders (SUDs),
      including alcohol, sedatives, tranquilizers, opioids, amphetamines, cannabis,
      cocaine, hallucinogens, heroin, and nicotine, in a nationally representative US
      adult sex-stratified sample. METHOD: Data were drawn from the National
      Epidemiologic Survey of Alcohol and Related Conditions (NESARC), a nationally
      representative US sample of adults aged 20 years and older (n = 34 653). Logistic
      regression models were conducted to understand the relations between 5 types of
      childhood maltreatment and SUDs separately among men and women after adjusting
      for sociodemographic variables and Diagnostic and Statistical Manual of Mental
      Disorders (DSM) Axis I and II mental disorders. RESULTS: All 5 types of childhood
      maltreatment were associated with increased odds of all individual SUDs among men
      and women after adjusting for sociodemographic variables, with the exception of
      physical neglect and heroin abuse or dependence, emotional neglect, and
      amphetamines and cocaine abuse or dependence among men (adjusted odds ratio range
      1.3 to 4.7). After further adjustment for other DSM Axis I and II mental
      disorders, the relations between childhood maltreatment and SUDs were attenuated,
      but many remained statistically significant. Differences in the patterns of
      findings were noted for men and women for sexual abuse and emotional neglect.
      CONCLUSIONS: This research provides evidence of the robust nature of the
      relations between many types of childhood maltreatment and many individual SUDs.
      The prevention of childhood maltreatment may help to reduce SUDs in the general
      population.

PMID- 23149284
TI  - Real-world evaluation of the Resident Assessment Instrument-Mental Health
      assessment system.
AB  - OBJECTIVE: We evaluated the Resident Assessment Instrument-Mental Health (RAI-MH)
      assessment platform at a large psychiatric hospital in Ontario during the 3 years
      following its provincially mandated implementation in 2005. Our objectives were
      to document and consider changes over time in front-line coding practices and in
      indicators of data quality. METHOD: Structured interviews with program staff were
      used for preliminary information-gathering on front-line coding practices. A
      retrospective data review of assessments conducted from 2005 to 2007 examined 5
      quantitative indicators of data quality. RESULTS: There is evidence of improved
      data quality over time; however, low scores on the outcome scales highlight
      potential shortcomings in the assessment system's ability to support outcome
      monitoring. There was variability in implementation and performance across
      clinical programs. CONCLUSIONS: This evaluation suggests that the RAI-MH-based
      assessment platform may be better suited to longer-term services for severely
      impaired clients than to short-term, highly specialized services. In particular,
      the suitability of the RAI-MH for hospital-based addictions care should be re
      examined. Issues of staff compliance and motivation and problems with assessment
      system performance would be highly entwined, making it inappropriate to attempt
      to allocate responsibility for areas of less than optimal performance to one or
      the other. The ability of the RAI-MH to perform well on clinical front lines is,
      in any case, essential for it to meet its objectives. Continued evaluation of
      this assessment platform should be a priority for future research.

PMID- 23149285
TI  - Predicting hospital length of stay for geriatric patients with mood disorders.
AB  - OBJECTIVE: To determine predictors of hospital length of stay (LOS) for adult and
      geriatric patients with mood disorders admitted to inpatient psychiatric beds.
      METHOD: Admission and discharge data from a large urban mental health centre,
      from 2005 to 2010 inclusive, were retrospectively analyzed. Using the Resident
      Assessment Instrument-Mental Health, an assessment that is used to collect
      demographic and clinical information within 72 hours of hospital admission, 199
      geriatric mood disorder admissions were compared with 570 adult mood disorder
      admissions. Predictors of hospital LOS were determined using a series of general
      linear models. RESULTS: Living alone, number of recent psychiatric admissions,
      involuntary admission, and close or constant observation level predict longer
      hospital LOS in geriatric, but not in adult mood disorder, patients. Conversely,
      pain on admission predicts shorter hospital LOS in geriatric, but not among
      adult, mood disorder patients. Predictors of longer hospital LOS, irrespective of
      admission group (adult, compared with geriatric), include incapacity, negative
      symptoms, and increased dependence for instrumental activities of daily living.
      CONCLUSIONS: Addressing these predictive factors early on during admission and in
      the community may result in shorter hospital LOS and more optimal use of
      resources.

PMID- 23149287
TI  - Sustainability and economic consequences of creating marine protected areas in
      multispecies multiactivity context.
AB  - The present study deals with harvesting of prey species in the presence of
      predator in a multispecies marine fishery. The total habitat is divided into two
      patches: one is reserve area where fishing is completely banned and other zone is
      called fishing area where only prey is exploited. We assume that the prey fish
      possesses heterogeneous intrinsic growth rate with uniform carrying capacity
      where as predator has constant intrinsic growth rate with prey dependent carrying
      capacity. The analytical conditions are derived to prevent the species extinction
      for larger employed effort in single (only prey) species fishery. Optimal
      equilibrium premium are presented for both monospecies and multispecies fishery
      for all degree of protection. Increasing standing stock (ISS) and protected
      standing stock (PSS) are measured in the presence of prey-predator interaction.

PMID- 23149288
TI  - The inhibitory activity of atractylenolide SH, a sesquiterpenoid, on IgE-mediated
      mast cell activation and passive cutaneous anaphylaxis (PCA).
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: AT SH, a sesquiterpenoid, is the major component
      of Atractylodes japonica Koidz that has been used as a traditional oriental
      medicine. AIM OF THE STUDY: We investigated the anti-allergic activity of AT SH
      and its mechanism of action. MATERIALS AND METHODS: The released amount of beta
      hexosaminidase in mast cells, a key parameter of degranulation, was measured.
      Anti-allergic potential of AT SH was evaluated using passive cutaneous
      anaphylaxis in vivo. The anti-allergic mechanism of AT SH was investigated by
      immunoblotting analysis, RT-PCR and measurement of [Ca(2+)]i in mast cells.
      RESULTS: AT SH significantly inhibited IgE/Ag-mediated degranulation with an
      IC(50) value (36 +/- 4 MUM) in RBL-2H3 cells without affecting cell viability. It
      also suppressed IgE/Ag-mediated passive cutaneous anaphylaxis (PCA) response with
      an ED(50) value (65 +/- 41 mg/kg) in vivo. AT SH suppressed the production of
      interleukin (IL-4) and tumor necrosis factor (TNF)-alpha mRNAs more potent than
      the Src-family kinase inhibitor PP2 in RBL-2H3 cells at all concentrations. In
      order to elucidate the anti-allergic mechanisms of AT SH in mast cells, we
      examined the activated levels of signaling molecules. AT SH inhibited the
      phosphorylation of Lyn, Fyn, Syk, LAT, PLCgamma, Gab2, Akt, p38, and JNK kinases
      expression. IgE/Ag-mediated [Ca(2+)]i elevation was significantly inhibited by AT
      SH. CONCLUSIONS: Our study suggests that AT SH might be used as a therapeutic
      agent for allergic diseases.

PMID- 23149286
TI  - Emerging risk factors for postpartum depression: serotonin transporter genotype
      and omega-3 fatty acid status.
AB  - OBJECTIVE: Depression is a leading cause of disability and hospitalization. Women
      are at the highest risk of depression during their childbearing years, and the
      birth of a child may precipitate a depressive episode in vulnerable women.
      Postpartum depression (PPD) is associated with diminished maternal somatic health
      as well as health and developmental problems in their offspring. This review
      focuses on 2 PPD risk factors of emerging interest: serotonin transporter (5-HTT)
      genotype and omega-3 polyunsaturated fatty acid (n-3 PUFA) status. METHOD: The
      MEDLINE, PubMed, and Web of Science databases were searched using the key words
      postpartum depression, nutrition, omega-3 fatty acids, and serotonin transporter
      gene. Studies were also located by reviewing the reference lists of selected
      articles. RESULTS: Seventy-five articles were identified as relevant to this
      review. Three carefully conducted studies reported associations between the 5-HTT
      genotype and PPD. As well, there is accumulating evidence that n-3 PUFA intake is
      associated with risk of PPD. Preliminary evidence suggests that there could be an
      interaction between these 2 emerging risk factors. However, further studies are
      required to confirm such an interaction and to elucidate the underlying
      mechanisms. CONCLUSIONS: Evidence to date supports a research agenda clarifying
      the associations between n-3 PUFAs, the 5-HTT genotype, and PPD. This is of
      particular interest owing to the high prevalence of poor n-3 PUFA intake among
      women of childbearing age and the consequent potential for alternative preventive
      measures and treatments for PPD.

PMID- 23149289
TI  - Indirubin, a purple 3,2- bisindole, inhibited allergic contact dermatitis via
      regulating T helper (Th)-mediated immune system in DNCB-induced model.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Indirubin, isolated from Indigo naturalis
      (Apiaceae) is a purple 3,2- bisindole and a stable isomer of indigo. Although it
      is known to have anti-inflammatory activities, its mechanism of action has not
      been elucidated. MATERIALS AND METHODS: Seven-week-old female BALB/c mice were
      sensitized with 1-chloro-2,4-dinitrobenzene (DNCB) to induce skin inflammation.
      Hematoxylin and eosin staining was performed to assess epidermal and dermal
      hyperplasia, which were determined by measuring the thicknesses of the epidermis
      and dermis, respectively. We also evaluated serum immunoglobulin E (IgE) levels
      and cytokines production, such as tumor necrosis factor (TNF)-alpha, interleukin
      (IL)-4, 6 and Interferon (IFN)-gamma. In addition, we investigated nuclear factor
      (NF)-kappaB, IkappaB-alpha and mitogen-activated protein (MAP) kinase activities
      for verifying the molecular mechanism of inflammation. RESULTS: Indirubin
      treatment suppressed skin inflammation in DNCB-exposed mice. The skin lesions
      were significantly thinner in the Indirubin-treated group than in untreated
      controls, and the hyperkeratosis disappeared. Indirubin reduced the total serum
      IgE level and cytokines production. In addition, it normalized NF-kappaB, IkappaB
      alpha and MAP kinase expression. CONCLUSIONS: Indirubin might be a useful
      treatment for allergic contact dermatitis via regulating the co-expression of T
      helper (Th) 1 and 2 cell-mediated immune responses.

PMID- 23149290
TI  - Effects of Korean red ginseng extract on the prevention of atopic dermatitis and
      its mechanism on early lesions in a murine model.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Korean red ginseng (KRG) has been shown to
      possess various biological activities including anti-inflammatory properties. AIM
      OF THE STUDY: We aimed to investigate the effects and mechanism of KRG on the
      prevention of atopic dermatitis (AD) using a mouse model. MATERIALS AND METHODS:
      The effect of KRG in trinitrochlorobenzene (TNCB)-treated NC/Nga mice was
      assessed by measuring ear thickness, transepidermal water loss (TEWL), total
      serum IgE, histologic changes of lesional skin, mRNA and protein expression of
      thymic stromal lymphopoietin (TSLP) and tumor necrosis factor (TNF)-alpha,
      immunohistochemistry for tissue interleukin (IL)-4, IL-17, and interferon (IFN)
      gamma. RESULTS: KRG significantly reduced ear thickness. Oral administration of
      KRG significantly prevented the increase in TEWL induced by TNCB. The serum IgE
      level was significantly lower in the KRG group. Histologically, lymphocyte
      infiltration was markedly decreased by KRG. CD1a positive (CD1a+) cells were
      diminished by KRG. Immunohistochemically, KRG significantly suppressed the
      protein expression of TSLP and TNF-alpha. The mRNA expression of TSLP in the
      lesions was significantly reduced by KRG. These results demonstrate that oral
      administration of KRG may inhibit the development of AD-like skin lesions in
      NC/Nga mice by modifying TSLP, DCs, and at least in part, the Th2 response.
      CONCLUSION: KRG may be a potential therapeutic modality for the prevention of AD.

PMID- 23149291
TI  - Differential diagnosis of a cystic abdominal mass: malignant transformation of
      the urachal cyst.

PMID- 23149292
TI  - Comparing cortical plasticity induced by conventional and high-definition 4 * 1
      ring tDCS: a neurophysiological study.
AB  - BACKGROUND: Transcranial direct current stimulation (tDCS) induces long-lasting
      NMDA receptor-dependent cortical plasticity via persistent subthreshold
      polarization of neuronal membranes. Conventional bipolar tDCS is applied with two
      large (35 cm(2)) rectangular electrodes, resulting in directional modulation of
      neuronal excitability. Recently a newly designed 4 * 1 high-definition (HD) tDCS
      protocol was proposed for more focal stimulation according to the results of
      computational modeling. HD tDCS utilizes small disc electrodes deployed in 4 * 1
      ring configuration whereby the physiological effects of the induced electric
      field are thought to be grossly constrained to the cortical area circumscribed by
      the ring. OBJECTIVE: We aim to compare the physiological effects of both tDCS
      electrode arrangements on motor cortex excitability. METHODS: tDCS was applied
      with 2 mA for 10 min. Fourteen healthy subjects participated, and motor cortex
      excitability was monitored by transcranial magnetic stimulation (TMS) before and
      after tDCS. RESULTS: Excitability enhancement following anodal and a respective
      reduction after cathodal stimulation occurred in both, conventional and HD tDCS.
      However, the plastic changes showed a more delayed peak at 30 min and longer
      lasting after-effects for more than 2 h after HD tDCS for both polarities, as
      compared to conventional tDCS. CONCLUSION: The results show that this new
      electrode arrangement is efficient for the induction of neuroplasticity in the
      primary motor cortex. The pattern of aftereffects might be compatible with the
      concept of GABA-mediated surround inhibition, which should be explored in future
      studies directly.

PMID- 23149294
TI  - Monitoring of metformin-induced lactic acidosis in a diabetic patient with acute
      kidney failure and effect of hemodialysis.
AB  - Metformin associated lactic acidosis (MALA) is a serious complication occurring
      especially in elderly patients given high doses of the drug. We report a non
      fatal case of MALA with pronounced acidosis (pH 6.76, lactate 30.81 mmol/l) and
      high metformin concentrations (127 mg/l) in a patient who had developed acute
      renal failure after undergoing an operation. Multiple measurements of biological
      parameters and metformin blood concentrations showed the effectiveness of
      repeated hemodialysis sessions on metformin elimination. Cases previously
      reported with such a severe MALA were associated with a high mortality rate. We
      show that close monitoring in an intensive care unit together with prompt and
      repeated dialysis sessions can lead to a favorable outcome.

PMID- 23149296
TI  - Liverpool care pathway is a half baked compromise.

PMID- 23149295
TI  - Effect of more frequent hemodialysis on cognitive function in the frequent
      hemodialysis network trials.
AB  - BACKGROUND: Cognitive impairment is common in patients with end-stage renal
      disease receiving hemodialysis 3 times per week. STUDY DESIGN: Randomized
      clinical trial. SETTING & PARTICIPANTS: 218 individuals participating in the
      Frequent Hemodialysis Network (FHN) Daily Trial and 81 participating in the FHN
      Nocturnal Trial. INTERVENTION: The Daily Trial tested in-center hemodialysis 6
      times per week versus 3 times per week. The Nocturnal Trial tested home nocturnal
      hemodialysis 6 times per week versus home or in-center hemodialysis 3 times per
      week. OUTCOMES: Cognitive function was measured at baseline, month 4, and month
      12. The primary outcome was performance on the Trail-Making Test, Form B, a
      measure of executive function, and a secondary outcome was performance on the
      Modified Mini-Mental State Examination, a measure of global cognition. The
      domains of attention, psychomotor speed, memory, and verbal fluency were assessed
      in 59 participants in the Daily Trial and 19 participants in the Nocturnal Trial.
      RESULTS: We found no benefit of frequent hemodialysis in either trial for the
      primary cognitive outcome (Daily Trial: OR for improvement, 0.99; 95% CI, 0.59
      1.66; Nocturnal Trial: OR, 1.19; 95% CI, 0.48-2.96). Similarly, there was no
      benefit of frequent hemodialysis in either trial on global cognition, the
      secondary cognitive outcome. Exploratory analyses in the Daily Trial suggested
      possible benefits of frequent hemodialysis for memory and verbal fluency, but not
      for attention and psychomotor speed. Exploratory analyses in the Nocturnal Trial
      suggested no benefit of frequent hemodialysis on attention, psychomotor speed,
      memory, or verbal fluency. LIMITATIONS: Unblinded intervention, small sample.
      CONCLUSIONS: Frequent hemodialysis did not improve executive function or global
      cognition.

PMID- 23149297
TI  - Synthesis and antioxidant activity of 1,3,4-oxadiazole tagged thieno[2,3
      d]pyrimidine derivatives.
AB  - This study represents the synthesis of a new series of N-substituted phenyl-5
      methyl-6-(5-(4-substituted phenyl)-1,3,4-oxadiazol-2-yl)thieno[2,3-d]pyrimidin-4
      amine derivatives (4a-l) and substituted phenylamino-5-methylthieno[2,3
      d]pyrimidine-6-carboxylic acid derivatives (3a-d). The newly synthesized
      compounds were characterized by (1)H NMR, (13)C NMR, LC-MS and IR analyses. All
      these novel compounds were screened for their in vitro antioxidant activity by
      employing DPPH, hydrogen peroxide, and nitric oxide radical scavenging assays.
      Compounds 4k, 4j, 4d, and 4e showed significant radical scavenging due to the
      presence of electron donating substituent on both sides of the thienopyrimidine
      ring enhances the activity and electron withdrawing groups like nitro decrease.

PMID- 23149293
TI  - The genome of the pear (Pyrus bretschneideri Rehd.).
AB  - The draft genome of the pear (Pyrus bretschneideri) using a combination of BAC-by
      BAC and next-generation sequencing is reported. A 512.0-Mb sequence corresponding
      to 97.1% of the estimated genome size of this highly heterozygous species is
      assembled with 194* coverage. High-density genetic maps comprising 2005 SNP
      markers anchored 75.5% of the sequence to all 17 chromosomes. The pear genome
      encodes 42,812 protein-coding genes, and of these, ~28.5% encode multiple
      isoforms. Repetitive sequences of 271.9 Mb in length, accounting for 53.1% of the
      pear genome, are identified. Simulation of eudicots to the ancestor of Rosaceae
      has reconstructed nine ancestral chromosomes. Pear and apple diverged from each
      other ~5.4-21.5 million years ago, and a recent whole-genome duplication (WGD)
      event must have occurred 30-45 MYA prior to their divergence, but following
      divergence from strawberry. When compared with the apple genome sequence, size
      differences between the apple and pear genomes are confirmed mainly due to the
      presence of repetitive sequences predominantly contributed by transposable
      elements (TEs), while genic regions are similar in both species. Genes critical
      for self-incompatibility, lignified stone cells (a unique feature of pear fruit),
      sorbitol metabolism, and volatile compounds of fruit have also been identified.
      Multiple candidate SFB genes appear as tandem repeats in the S-locus region of
      pear; while lignin synthesis-related gene family expansion and highly expressed
      gene families of HCT, C3'H, and CCOMT contribute to high accumulation of both G
      lignin and S-lignin. Moreover, alpha-linolenic acid metabolism is a key pathway
      for aroma in pear fruit.

PMID- 23149298
TI  - Synthesis of fluorescent ristocetin aglycon derivatives with remarkable
      antibacterial and antiviral activities.
AB  - Isoindole and benzoisoindole derivatives of ristocetin aglycon have been prepared
      by reaction with o-phthalaldehyde or naphthalene-2,3-dialdehyde and various
      thiols. The new compounds exhibited potent antibacterial and anti-influenza virus
      activity. The cluster forming and fluorescent properties of the aglycon
      derivatives were also studied.

PMID- 23149299
TI  - Design, synthesis and biological evaluation of 5-hydroxy, 5-substituted
      pyrimidine-2,4,6-triones as potent inhibitors of gelatinases MMP-2 and MMP-9.
AB  - Matrix metalloproteinases (MMPs) are attractive biological targets that play a
      key role in many physiopathological processes such as degradation of
      extracellular matrix proteins, release and cleavage of cell-surface receptors,
      tumour progression, homeostatic regulation and innate immunity. A series of 5
      hydroxy, 5-substituted pyrimidine-2,4,6-triones were rationally designed,
      prepared and tested as inhibitors of gelatinases MMP-2 and MMP-9 and collagenase
      MMP-8. On one side, the presence of the 5-hydroxyl group, that represents an
      typical feature of this class of compounds, ensured an attractive pharmacokinetic
      profile while on the other suitably substituted biaryl molecular fragments,
      attached to position 5 through a ketomethylene linker, guaranteed favourable
      interaction in the deep region of the S(1)' enzymatic subsite. This rational
      design led to the discovery of highly potent MMP inhibitors. In particular,
      biphenyl derivatives bearing at the para position COCH(3) and OCF(3) substituents
      permitted to inhibit gelatinases MMP-2 and MMP-9, with IC(50) values as low as 30
      nM and 21 nM, respectively, whereas the introduction at the same position of the
      bulkier SO(2)CH(3) group afforded a potent collagenase MMP-8 inhibitor with an
      IC(50) value equal to 66 nM. Molecular docking simulations allowed us to
      elucidate key interactions driving the binding of the top active compounds
      towards their preferred MMP target.

PMID- 23149300
TI  - A fuel-cell-assisted iron redox process for simultaneous sulfur recovery and
      electricity production from synthetic sulfide wastewater.
AB  - Sulfide present in wastewaters and waste gases should be removed due to its
      toxicity, corrosivity, and malodorous property. Development of effective, stable,
      and feasible methods for sulfur recovery from sulfide attains a double objective
      of waste minimization and resource recovery. Here we report a novel fuel-cell
      assisted iron redox (FC-IR) process for simultaneously recovering sulfur and
      electricity from synthetic sulfide wastewater. The FC-IR system consists of an
      oxidizing reactor where sulfide is oxidized to elemental sulfur by Fe(III), and a
      fuel cell where Fe(III) is regenerated from Fe(II) concomitantly with electricity
      producing. The oxidation of sulfide by Fe(III) is significantly dependent on
      solution pH. Increasing the pH from 0.88 to 1.96 accelerates the oxidation of
      sulfide, however, lowers the purity of the produced elemental sulfur. The
      performance of fuel cell is also a strong function of solution pH. Fe(II) is
      completely oxidized to Fe(III) when the fuel cell is operated at a pH above 6.0,
      whereas only partially oxidized below pH 6.0. At pH 6.0, the highest columbic
      efficiency of 75.7% is achieved and electricity production maintains for the
      longest time of 106 h. Coupling operation of the FC-IR system obtains sulfide
      removal efficiency of 99.90%, sulfur recovery efficiency of 78.6 +/- 8.3%, and
      columbic efficiency of 58.6 +/- 1.6%, respectively. These results suggest that
      the FC-IR process is a promising tool to recover sulfur and energy from sulfide.

PMID- 23149301
TI  - Dividing attention between two transparent motion surfaces results in a failure
      of selective attention.
AB  - In object-based attention, it is easier to divide attention between features
      within a single object than between features across objects. In this study we
      test the prediction of several capacity models in order to best characterize the
      cost to dividing attention between objects. Here we studied behavioral
      performance on a divided attention task in which subjects attended to the motion
      and luminance of overlapping random dot kinemategrams, specifically red upward
      moving dots superimposed with green downward moving dots. Subjects were required
      to detect brief changes (transients) in the motion or luminance within the same
      surface or across different surfaces. There were two primary results. First, the
      dual-task deficit was large when attention was divided across two surfaces and
      near zero when attention was divided within a surface. This is consistent with
      limited-capacity processing across surfaces and unlimited-capacity processing
      within a surface-a pattern predicted by established theories of object-based
      attention. Second and unexpectedly, there was evidence of crosstalk between
      features: when cued to monitor transients on one surface, response rates were
      inflated by the presence of a transient on the other surface. Such crosstalk is a
      failure of selective attention between surfaces.

PMID- 23149302
TI  - [Differentiated thyroid cancer in childhood].
AB  - Thyroid carcinoma is a rare disease in children, and is mostly of the papillary
      histological type. Lymph node metastases are frequent at diagnosis, being present
      in 23 to 74% of the cases and can reveal the cancer in about one fourth of cases.
      Lung metastases are present at initial diagnosis in 6 to 20% of cases. The main
      known risk factor for thyroid cancer is a previous history of radiation exposure.
      Treatment includes surgery with total thyroidectomy and lymph node dissection and
      radioiodine therapy in case of extensive disease and distant metastases. Life
      long thyroxine treatment is given to all patients. Long term prognosis is
      favourable, but thyroid cancer related deaths have been reported some decades
      after initial treatment.

PMID- 23149303
TI  - Current state of three-dimensional myocardial strain estimation using
      echocardiography.
AB  - With the developments in ultrasound transducer technology and both hardware and
      software computing, real-time volumetric imaging has become widely available,
      accompanied by various methods of assessing three-dimensional (3D) myocardial
      strain, often referred to as 3D speckle-tracking echocardiographic methods.
      Indeed, these methods should provide cardiologists with a better view of regional
      myocardial mechanics, which might be important for diagnosis, prognosis, and
      therapy. However, currently available 3D speckle-tracking echocardiographic
      methods are based on different algorithms, which introduce substantial
      differences between them and make them not interchangeable with each other.
      Therefore, it is critical that each 3D speckle-tracking echocardiographic method
      is validated individually before being introduced into clinical practice. In this
      review, the authors discuss differences and similarities of the currently
      available 3D strain estimation approaches and provide an overview of the current
      status of their validation.

PMID- 23149304
TI  - Isolation and synthesis of two antiproliferative calamenene-type sesquiterpenoids
      from Sterculia tavia from the Madagascar rain forest.
AB  - Investigation of the endemic Madagascan plant Sterculia taiva Baill. (Malvaceae)
      for antiproliferative activity against the A2780 ovarian cancer cell line led to
      the isolation of two new bioactive calamenene-type sesquiterpenoids, named
      tavinin A (2) and epi-tavinin A (3) together with the known sesquiterpenoid
      mansonone G (1). The structures of the two new compounds were elucidated based on
      analysis of their 1D and 2D NMR spectra and mass spectrometric data, and were
      confirmed by de novo synthesis. The three isolated sesquiterpenoids (1-3) had
      modest antiproliferative activities against the A2780 ovarian cancer cell line,
      with IC(50) values of 10.2, 5.5 and 6.7 MUM, respectively.

PMID- 23149305
TI  - Characterization of rifampin-resistant isolates of Mycobacterium tuberculosis
      from Sichuan in China.
AB  - Rifampin is a key component of standard short-course first-line therapy against
      Mycobacterium tuberculosis, and rifampin resistance of this pathogen has been
      reported to be related to rpoB gene mutations. The objective of this study was to
      characterize the rpoB gene mutations in rifampin-resistant M. tuberculosis
      isolates circulated in Sichuan. Sequencing of rpoB gene and spoligotyping were
      performed on 268 randomly selected isolates from January 2008 to May 2010. The
      results indicated that 207 (97.2%) rifampin-resistant isolates had mutations at
      26 codons in the amplified region with 50 different genotypes, while 1 (1.8%) of
      55 susceptible isolates had a nonsense mutation. The most common mutations were
      in codon 531 (55.9%), 526 (16.4%), 516 (10.3%) and 511 (8.9%). Among the 213
      resistant isolates, 150 (70.4%) belonged to the Beijing family and mutation at
      codon 531 (TCG->TTG) was associated with Beijing genotype (chi(2), 9.8305; p,
      0.0017). It is demonstrated that the frequency of 511 (CTG->CCG) mutations in
      Sichuan was higher than in other provinces of China, as well as other geographic
      regions worldwide. It is suggested that only a small portion (2.7%) of rifampin
      resistant Beijing genotype isolates in Sichuan be spread by clonal expansion
      during the study period.

PMID- 23149306
TI  - Participatory diagnosis and prioritization of constraints to cattle production in
      some smallholder farming areas of Zimbabwe.
AB  - A participatory epidemiological study was conducted to identify and prioritize
      constraints to livestock health and production on smallholder farms in Sanyati
      and Gokwe districts of Zimbabwe. Questionnaires were administered to 294 randomly
      selected livestock owners across the two districts. Livestock diseases (29% of
      the respondents), high cost of drugs (18.21%), weak veterinary extension
      (15.18%), inadequate grazing (13.60%), inadequate water (13.54%), and livestock
      thefts (10.44%) were the major livestock health and production constraints
      identified. The number of diseases reported varied (P<0.05) with livestock
      species and nature of causative agent. Out of the 36 diseases mentioned by
      farmers, 50%, 22.2%, 19.4%, 5.5% and 2.8% were diseases of cattle, sheep and
      goats, domestic chicken, donkeys, and guinea fowls, respectively. Seven (19.4%)
      of the 36 diseases including rabies and foot and mouth disease were those listed
      by the OIE. Thirty-four percent of the respondents rated bovine dermatophilosis
      as the most important livestock disease. Respondents rated, in descending order,
      other diseases including tick borne diseases (21%); a previously unreported
      disease, "Magwiriri" or "Ganda renzou" in vernacular (14%); mastitis (11%);
      parafilariosis (11%); and blackleg (9%). Cattle skin samples from "Magwiriri"
      cases had Besnoitia besnoiti parasites. Overall, this study revealed factors and
      diseases that limit livestock production in Zimbabwe and are of global concern;
      in addition, the study showed that the skin diseases, bovine dermatophilosis and
      besnoitiosis, have recently emerged and appear to be spreading, likely a
      consequence of ectoparasite control demise in smallholder farming areas of
      Zimbabwe over the last 15 years.

PMID- 23149307
TI  - A 20-year experience with surgical management of true and false internal carotid
      artery aneurysms.
AB  - AIM OF THE STUDY: The aim of this study was to retrospectively analyse early and
      late results of surgical management of internal carotid artery (ICA) true and
      false aneurysms in a single-centre experience. MATERIALS AND METHODS: From
      January 1988 to December 2011, 50 consecutive interventions for ICA aneurismal
      disease were performed; interventions were performed for true ICA aneurysm in 19
      cases (group 1) and for ICA post-carotid endarterectomy (CEA) pseudo-aneurysm in
      the remaining 31 (group 2). Early results (<30 days) were evaluated in terms of
      mortality, stroke and cranial nerves' injury and compared between the two groups
      with chi(2) test. Follow-up results (stroke free-survival, freedom from ICA
      thrombosis and reintervention) were analysed with Kaplan-Meier curves and
      compared with log-rank test. RESULTS: All the patients in group 1 had open repair
      of their ICA aneurysm; in group 2 open repair was performed in 30 cases, while
      three patients with post-CEA aneurysm without signs of infection had a covered
      stent placed. There were no perioperative deaths. Two major strokes occurred in
      group 1 and one major stroke occurred in group 2 (p = 0.1). The rates of
      postoperative cranial nerve injuries were 10.5% in group 1 and 13% in group 2 (p
      = 0.8). Median duration of follow-up was 60 months (range 1-276). Estimated 10
      year stroke-free survival rates were 64% in group 1 and 37% in group 2 (p = 0.4,
      log rank 0.5); thrombosis-free survival at 10 years was 66% in group 1 and 34% in
      group 2 (p = 0.2, log rank 1.2), while the corresponding figures in terms of
      reintervention-free survival were 68% and 33%, respectively (p = 0.2, log rank
      1.8). CONCLUSIONS: Surgical treatment of ICA aneurismal disease provided in our
      experience satisfactory early and long-term results, without significant
      differences between true and false aneurysms. In carefully selected patients with
      non-infected false aneurysm, the endovascular option seems to be feasible.

PMID- 23149308
TI  - Illuminating the fog that surrounds chimney grafts: Commentary on: Triple-barrel
      graft as a novel strategy to preserve supra-aortic branches in arch-TEVAR
      procedures.

PMID- 23149309
TI  - Physical strain of walking relates to activity level in adults with cerebral
      palsy.
AB  - OBJECTIVE: To gain insight into underlying mechanisms of inactive lifestyles
      among adults with spastic bilateral cerebral palsy (CP) with a focus on aerobic
      capacity, oxygen consumption, and physical strain during walking at preferred
      walking speed, as well as fatigue. DESIGN: Cross-sectional. SETTING: University
      hospital. PARTICIPANTS: Adults (N=36), aged 25 to 45 years, with spastic
      bilateral CP, walking with (n=6) or without (n=30) walking aids. INTERVENTIONS:
      Not applicable. MAIN OUTCOME MEASURES: Physical strain during walking was defined
      as oxygen uptake during walking, expressed as percentage of peak aerobic
      capacity. Participants with spastic bilateral CP walked their preferred walking
      speed while oxygen uptake was measured using a portable gas analyzer. Peak
      aerobic capacity was measured during maximal cycle ergometry. An accelerometry
      based activity monitor measured total daily walking time. Regression analyses
      were performed to assess the relation between aerobic capacity, oxygen uptake,
      and physical strain of walking on the one hand and total daily walking time on
      the other hand. RESULTS: Neither aerobic capacity nor oxygen uptake during
      walking was related to total daily walking time (r(2)=.29, P=.10 and r(2)=.27,
      P=.16, respectively). Physical strain of walking at preferred walking speed was
      inversely related to total daily walking time (r(2)=.44, P<.01). CONCLUSIONS:
      Physical strain during walking is moderately related to total daily walking time,
      implying that people with high physical strain during walking at preferred
      walking speed likely walk less in daily life.

PMID- 23149310
TI  - Community participation measures for people with disabilities: a systematic
      review of content from an international classification of functioning, disability
      and health perspective.
AB  - OBJECTIVE: To identify instruments that measure community participation in people
      with disabilities and to evaluate which domains, to what extent, and how
      precisely they address this construct. The review aims to provide information to
      guide the selection of community participation instruments and to identify
      limitations of existing measures. DATA SOURCES: A systematic search was performed
      in PubMed, CINAHL, and PsychINFO in February and March 2012. The latest
      systematic reviews and references of searched articles were also reviewed to
      check for measures that were not identified in the initial search. STUDY
      SELECTION: Instruments were included if they (1) were a self-report
      questionnaire; (2) measured community participation, participation, or community
      integration; (3) measured actual participation (rather than subjective
      experience); (4) had available information on the instrument content and
      measurement properties; (5) were designed for adults; and (6) were applicable for
      all disabled populations. DATA EXTRACTION: Instruments were obtained from
      identified full-text articles, reference lists, or websites. Two researchers
      independently reviewed each selected instrument to determine which of their items
      measure community participation. These items were then classified using 9
      community participation domains from the International Classification of
      Functioning, Disability and Health to reflect each instrument's domain coverage.
      DATA SYNTHESIS: Seventeen instruments were identified as containing community
      participation items, 2 of which were 100% composed of community participation
      items. The rest of the instruments included 8.7% to 73.1% items measuring
      community participation. The domain coverage varied from 3 to 8 domains across
      the instruments. CONCLUSIONS: None of the 17 instruments covered the full breadth
      of community participation domains, but each addressed community participation to
      some extent. New instruments that evaluate community participation more
      comprehensively will be needed in the future.

PMID- 23149311
TI  - Effectiveness of intra-articular hyaluronic acid for ankle osteoarthritis
      treatment: a systematic review and meta-analysis.
AB  - OBJECTIVES: To explore the effectiveness and safety of hyaluronic acid (HA)
      administration for ankle osteoarthritis (OA), and to investigate the effects of
      variations in HA regimens on treatment responses. DATA SOURCES: Electronic
      databases, including PubMed and Scopus, were searched from January 1995 to June
      2012. STUDY SELECTION: We included randomized controlled trials (RCTs) or
      prospective cohort studies that employed intra-articular HA to treat ankle OA.
      Four RCTs, 1 comparative study, and 4 single-arm prospective studies were
      identified, comprising 354 participants. DATA EXTRACTION: We determined effect
      sizes for selected studies by extracting pain scores from ankle OA or visual
      analog scales before and after HA or reference treatments. Meta-regression was
      implemented to determine whether outcomes were modified by variations in HA
      regimens. DATA SYNTHESIS: The pooled effect size of improvement scores from
      baseline was 2.01 (95% confidence interval [CI], 1.27-2.75), whereas the values
      of comparisons with reference treatments including saline, exercise, and
      arthroscopy reduced to 0.85 (95% CI, -0.13 to 1.83). The placebo effect of the
      injection procedure accounted for 87% of the observed efficacy of HA treatment.
      The meta-regression indicated that the molecular weight was not associated with
      the magnitude of pain relief, but increases in total doses and active ingredients
      administered might result in a better outcome. Conversely, increases in injection
      volumes might cause a reduction of effect sizes. Regarding the side effects, the
      use of extremely high molecular weight HA frequently caused early postinjection
      pain. CONCLUSIONS: Intra-articular HA administration can significantly reduce
      pain in ankle OA compared with the condition before treatment, and it is likely
      superior to reference therapy. We recommend using multiple doses with an
      appropriate injection volume to achieve maximum effectiveness.

PMID- 23149312
TI  - Cancer incidence and patient survival rates among the residents in the Pudong New
      Area of Shanghai between 2002 and 2006.
AB  - With the growing threat of malignancy to health, it is necessary to analyze
      cancer incidence and patient survival rates among the residents in Pudong New
      Area of Shanghai to formulate better cancer prevention strategies. A total of
      43,613 cancer patients diagnosed between 2002 and 2006 were recruited from the
      Pudong New Area Cancer Registry. The incidence, observed survival rate, and
      relative survival rate of patients grouped by sex, age, geographic area, and TNM
      stage were calculated using the Kaplan-Meier, life table, and Ederer II methods,
      respectively. Between 2002 and 2006, cancer incidence in Pudong New Area was
      349.99 per 100,000 person-years, and the 10 most frequently diseased sites were
      the lung, stomach, colon and rectum, liver, breast, esophagus, pancreas, brain
      and central nervous system, thyroid, and bladder. For patients with cancers of
      the colon and rectum, breast, thyroid, brain and central nervous system, and
      bladder, the 5-year relative survival rate was greater than 40%, whereas patients
      with cancers of the liver and pancreas had a 5-year relative survival rate of
      less than 10%. The 1-year to 5-year survival rates for patients grouped by sex,
      age, geographic area, and TNM stage differed significantly (all P < 0.001). Our
      results indicate that cancer incidence and patient survival in Pudong New Area
      vary by tumor type, sex, age, geographic area, and TNM stage. 

PMID- 23149313
TI  - Suppressing tumor growth of nasopharyngeal carcinoma by hTERTC27 polypeptide
      delivered through adeno-associated virus plus adenovirus vector cocktail.
AB  - Nasopharyngeal carcinoma(NPC) is a metastatic carcinoma that is highly prevalent
      in Southeast Asia. Our laboratory has previously demonstrated that the C-terminal
      27-kDa polypeptide of human telomerase reverse transcriptase (hTERTC27) inhibits
      the growth and tumorigenicity of human glioblastoma and melanoma cells. In this
      study, we investigated the antitumor effect of hTERTC27 in human C666-1 NPC cells
      xenografted in a nude mouse model. A cocktail of vectors comprising recombinant
      adeno-associated virus (rAAV) and recombinant adenovirus (rAdv) that each carry
      hTERTC27 (rAAV-hTERTC27 and rAdv-hTERTC27; the cocktail was abbreviated to
      rAAV/rAdv-hTERTC27) was more effective than either rAAV-hTERTC27 or rAdv-hTERTC27
      alone in inhibiting the growth of C666-1 NPC xenografts. Furthermore, we
      established three tumors on each mouse and injected rAAV/rAdv-hTERTC27 into one
      tumor per mouse. Although hTERTC27 expression could only be detected in the
      injected tumors, reduced tumor growth was observed in the injected tumor as well
      as the uninjected tumors, demonstrating that the vector cocktail could provoke an
      antitumor effect on distant, metastasized tumors. Further studies showed the
      observed antitumor effects included inducing necrosis and apoptosis and reducing
      microvessel density. Together, our data suggest that the rAAV/rAdv-hTERTC27
      cocktail can potently inhibit NPC tumor growth in both local and metastasized
      tumors and should be further developed as a novel gene therapy strategy for NPC.

PMID- 23149315
TI  - Dynamic protein-protein interaction subnetworks of lung cancer in cases with
      smoking history.
AB  - Smoking is the primary cause of lung cancer and is linked to 85% of lung cancer
      cases. However, how lung cancer develops in patients with smoking history remains
      unclear. Systems approaches that combine human protein-protein interaction (PPI)
      networks and gene expression data are superior to traditional methods. We
      performed these systems to determine the role that smoking plays in lung cancer
      development and used the support vector machine (SVM) model to predict PPIs. By
      defining expression variance (EV), we found 520 dynamic proteins (EV>0.4) using
      data from the Human Protein Reference Database and Gene Expression Omnibus
      Database, and built 7 dynamic PPI subnetworks of lung cancer in patients with
      smoking history. We also determined the primary functions of each subnetwork:
      signal transduction, apoptosis, and cell migration and adhesion for subnetwork A;
      cell-sustained angiogenesis for subnetwork B; apoptosis for subnetwork C; and,
      finally, signal transduction and cell replication and proliferation for
      subnetworks D-G. The probability distribution of the degree of dynamic protein
      and static protein differed, clearly showing that the dynamic proteins were not
      the core proteins which widely connected with their neighbor proteins. There were
      high correlations among the dynamic proteins, suggesting that the dynamic
      proteins tend to form specific dynamic modules. We also found that the dynamic
      proteins were only correlated with the expression of selected proteins but not
      all neighbor proteins when cancer occurred.

PMID- 23149314
TI  - The mechanism of the anticancer function of M1 macrophages and their use in the
      clinic.
AB  - M1-type macrophages are capable of inducing lysis in various types of cancer
      cells, but the mechanism of action is unclear. It has been noted that an "unknown
      protein" produced together with protease by activated macrophages is responsible
      for this action. Activated M1 macrophages have been recently reported to produce
      family 18 chitinases, all of which have been named chitotriosidase. Our
      experiments have demonstrated that family 18 chitinases work together with
      proteases and can damage various cancer cells both in vitro and in vivo. Thus, in
      this article, we suggest that the 50-kDa chitotriosidase is the reported "unknown
      protein". In addition, we discuss how to properly stimulate activated M1
      macrophages to produce 50-kDa chitotriosidases and proteases for destroying
      cancer cells. Because family 19 chitinase has recently been reported to kill
      cancer cells, we also discuss the possibility of directly using human family 18
      chitotriosidase and the humanized plant family 19 chitinase for cancer treatment.

PMID- 23149316
TI  - The frequency of alcohol, illicit and licit drug consumption in the general
      driving population in South-East Hungary.
AB  - In the framework of the DRUID (Driving under the Influence of Drugs, Alcohol, and
      Medicines) EU-6 project, a roadside survey was performed in South-East Hungary to
      determine the incidence of alcohol and the most frequent illicit and licit drug
      consumption (amphetamines, THC, illicit and medical opiates, cocaine, ketamine,
      benzodiazepines, zopiclone and zolpidem) in the general driving population. All
      3110 drivers stopped between 01 January 2008 and 31 December 2009 were checked
      for alcohol, and among them 2738 persons (87.7%) participated in the further
      examinations, on a voluntary basis. Licit and illicit drugs were determined from
      their oral fluid samples by GC-MS analysis. Illicit drugs were detected in 27
      cases (0.99%), licit drugs in 85 cases (3.14%), and alcohol (cut off: 0.1g/l) was
      found in 4 (0.13%) cases. Illicit drug consumption was the highest among men of
      the ages 18-34, during the spring, and on the week-end nights. With respect to
      licit drugs, the highest incidence was found among women over the age of 50,
      during the summer, and on the week-days. All alcohol positive cases were men over
      the age of 35. In comparison to international European averages, the alcohol and
      illicit drug consumption was low, but the licit drug consumption was over the
      European average.

PMID- 23149317
TI  - Damage due to lightning when it strikes the face.
AB  - A case of death due to lightning is discussed in reference to autopsy findings
      that revealed damage to the tongue, pharynx, larynx, sclera and oesophagus for
      the first time. The damage described in the present paper must be considered when
      there is direct lightning strike on the face.

PMID- 23149318
TI  - Image copy-move forgery detection based on polar cosine transform and approximate
      nearest neighbor searching.
AB  - Copy-move is one of the most commonly used image tampering operation, where a
      part of image content is copied and then pasted to another part of the same
      image. In order to make the forgery visually convincing and conceal its trace,
      the copied part may subject to post-processing operations such as rotation and
      blur. In this paper, we propose a polar cosine transform and approximate nearest
      neighbor searching based copy-move forgery detection algorithm. The algorithm
      starts by dividing the image into overlapping patches. Robust and compact
      features are extracted from patches by taking advantage of the rotationally
      invariant and orthogonal properties of the polar cosine transform. Potential copy
      move pairs are then detected by identifying the patches with similar features,
      which is formulated as approximate nearest neighbor searching and accomplished by
      means of locality-sensitive hashing (LSH). Finally, post-verifications are
      performed on potential pairs to filter out false matches and improve the accuracy
      of forgery detection. To sum up, the LSH based similar patch identification and
      the post-verification methods are two major novelties of the proposed work.
      Experimental results reveal that the proposed work can produce accurate detection
      results, and it exhibits high robustness to various post-processing operations.
      In addition, the LSH based similar patch detection scheme is much more effective
      than the widely used lexicographical sorting.

PMID- 23149319
TI  - Youth psychopathy: Differential correlates of callous-unemotional traits,
      narcissism, and impulsivity.
AB  - Research supports the validity of the dimensional approach to psychopathy in both
      children and adults. The occurrence of severe aggressive and antisocial behavior
      in combination with callous-unemotional traits (CU traits) designates a group of
      children that is particularly at risk to develop psychopathy. However, most
      studies did not investigate the role of the remaining psychopathy dimensions
      (i.e. narcissism and impulsivity) in comparison. The present text reviews the
      newest developments in the dimensional study of psychopathy in relation to
      cognition, behavior and affect in clinical and detained child and adolescent
      samples. Findings support the role of the callous-unemotional dimension (CU
      traits) in the development of psychopathy. Additionally, they also underscore the
      importance of the narcissistic and impulsive dimensions for the understanding of
      psychopathy in children and adolescents and for the identification of different
      psychopathy profiles. Understanding differential correlates of the underlying
      dimensions of psychopathy is an important step in formulating interventions for
      those most at risk.

PMID- 23149320
TI  - Prevention and intervention.

PMID- 23149321
TI  - Corridor-level signalized intersection safety analysis in Shanghai, China using
      Bayesian hierarchical models.
AB  - Most traffic crashes in Chinese cities occur at signalized intersections.
      Research on the intersection safety problem in China is still in its early stage.
      The recent development of an advanced traffic information system in Shanghai
      enables in-depth intersection safety analyses using road design, traffic
      operation, and crash data. In Shanghai, the road network density is relatively
      high and the distance between signalized intersections is small, averaging about
      200m. Adjacent signalized intersections located along the same corridor share
      similar traffic flows, and signals are usually coordinated. Therefore, when
      studying intersection safety in Shanghai, it is essential to account for
      intersection correlations within corridors. In this study, data for 195
      signalized intersections along 22 corridors in the urban areas of Shanghai were
      collected. Mean speeds and speed variances of corridors were acquired from taxis
      equipped with Global Positioning Systems (GPS). Bayesian hierarchical models were
      applied to identify crash risk factors at both the intersection and the corridor
      levels. Results showed that intersections along corridors with lower mean speeds
      were associated with fewer crashes than those with higher speeds, and those
      intersections along two-way roads, under elevated roads, and in close proximity
      to each other, tended to have higher crash frequencies.

PMID- 23149322
TI  - Cervical and thoracic spine injury from interactions with vehicle roofs in pure
      rollover crashes.
AB  - Around one third of serious injuries sustained by belted, non-ejected occupants
      in pure rollover crashes occur to the spine. Dynamic rollover crash test
      methodologies have been established in Australia and the United States, with the
      aims of understanding injury potential in rollovers and establishing the basis of
      an occupant rollover protection crashworthiness test protocol that could be
      adopted by consumer new car assessment programmes and government regulators
      internationally. However, for any proposed test protocol to be effective in
      reducing the high trauma burden resulting from rollover crashes, appropriate
      anthropomorphic devices that replicate real-world injury mechanisms and
      biomechanical loads are required. To date, consensus regarding the combination of
      anthropomorphic device and neck injury criteria for rollover crash tests has not
      been reached. The aim of the present study is to provide new information
      pertaining to the nature and mechanisms of spine injury in pure rollover crashes,
      and to assist in the assessment of spine injury potential in rollover crash
      tests. Real-world spine injury cases that resulted from pure rollover crashes in
      the United States between 2000 and 2009 are identified, and compared with cadaver
      experiments under vertical load by other authors. The analysis is restricted to
      contained, restrained occupants that were injured from contact with the vehicle
      roof structure during a pure rollover, and the role of roof intrusion in creating
      potential for spine injury is assessed. Recommendations for assessing the
      potential for spine injury in rollover occupant protection crash test protocols
      are made.

PMID- 23149323
TI  - Sleepy driving on the real road and in the simulator--A comparison.
AB  - Sleepiness has been identified as one of the most important factors contributing
      to road crashes. However, almost all work on the detailed changes in behavior and
      physiology leading up to sleep related crashes has been carried out in driving
      simulators. It is not clear, however, to what extent simulator results can be
      generalized to real driving. This study compared real driving with driving in a
      high fidelity, moving base, driving simulator with respect to driving
      performance, sleep related physiology (using electroencephalography and
      electrooculography) and subjective sleepiness during night and day driving for 10
      participants. The real road was emulated in the simulator. The results show that
      the simulator was associated with higher levels of subjective and physiological
      sleepiness than real driving. However, both for real and simulated driving, the
      response to night driving appears to be rather similar for subjective sleepiness
      and sleep physiology. Lateral variability was more responsive to night driving in
      the simulator, while real driving at night involved a movement to the left in the
      lane and a reduction of speed, both of which effects were absent in the
      simulator. It was concluded that the relative validity of simulators is
      acceptable for many variables, but that in absolute terms simulators cause higher
      sleepiness levels than real driving. Thus, generalizations from simulators to
      real driving must be made with great caution.

PMID- 23149324
TI  - Predictive and epidemiologic modeling of the spatial risk of human onchocerciasis
      using biophysical factors: a case study of Ghana and Burundi.
AB  - Although recent efforts taken have substantially contained human onchocerciasis
      in many African countries, published reports indicate a recrudescence of the
      disease. To understand this problem, biophysical factors that favor the
      establishment of human onchocerciasis in Ghana and Burundi-countries identified
      as threat locations of recrudescence for neighboring countries-were analyzed.
      Data pertaining to the prevalence of human onchocerciasis in both countries was
      obtained from published sources. Findings in this study suggest that there was a
      gradient in prevalence of onchocerciasis in geographic locations near the water
      streams. The predictive models suggest that rainfall, humidity, and elevation
      were statistically significant for Burundi data while in Ghana, only the effect
      of elevation was highly significant (p<0.0001). In 2010, the estimated at-risk
      population was 4,817,280 people (19.75% of the total population) and 522,773
      people (6.23% of the total population) in Ghana and Burundi, respectively.
      Findings can help in the effective design of preventive control measures.

PMID- 23149325
TI  - Using geospatial technologies to explore activity-based retail food environments.
AB  - Several studies have demonstrated relationships between neighborhood-level retail
      food environments and obesity, race/ethnicity, and socioeconomic status. Most,
      however, have been limited by the use of residential neighborhoods to define food
      environments. This study recruited 121 participants to supply three days of
      Global Positioning System (GPS) tracking data to explore daily activity spaces
      and food environments. Participants also answered two surveys regarding personal
      characteristics, and diet and food purchasing. Several food environment measures
      were calculated for food locations within a half-mile of their GPS tracks. Non
      parametric statistics examined (1) differences between activity- and neighborhood
      based food environments, (2) associations between personal characteristics and
      activity-based food environments, and (3) associations between diet, purchasing,
      and activity-based food environments. Activity- and neighborhood-based food
      environments were significantly different. Several associations were observed
      among activity-based food environment measures and personal characteristics.
      Dietary intake, food purchasing, and obesity were associated with some activity
      based food environment measures.

PMID- 23149326
TI  - Performance of cancer cluster Q-statistics for case-control residential
      histories.
AB  - Few investigations of health event clustering have evaluated residential
      mobility, though causative exposures for chronic diseases such as cancer often
      occur long before diagnosis. Recently developed Q-statistics incorporate human
      mobility into disease cluster investigations by quantifying space- and time
      dependent nearest neighbor relationships. Using residential histories from two
      cancer case-control studies, we created simulated clusters to examine Q-statistic
      performance. Results suggest the intersection of cases with significant
      clustering over their life course, Q(i), with cases who are constituents of
      significant local clusters at given times, Q(it), yielded the best performance,
      which improved with increasing cluster size. Upon comparison, a larger proportion
      of true positives were detected with Kulldorf's spatial scan method if the time
      of clustering was provided. We recommend using Q-statistics to identify when and
      where clustering may have occurred, followed by the scan method to localize the
      candidate clusters. Future work should investigate the generalizability of these
      findings.

PMID- 23149327
TI  - The effect of presence of infected neighbouring farms for the Campylobacter
      infection status in Danish broiler farms.
AB  - Neighbourhood risk factors for Campylobacter infection in Danish broilers were
      evaluated. Campylobacter infection status of a flock was identified by PCR
      analysis of cloacal swab samples collected as a part of national surveillance
      program. Included into the study were, in total, 10,876 broiler flocks sent by
      226 farms to processing plants from 2007 to 2009. A multivariable logistic
      regression model with autocorrelation structure was used to model the effect of
      exposure variables on the probability of being tested positive to Campylobacter.
      Results showed a significant protective effect with the absence of infected
      neighbours within a distance of 2 km. The analysis was adjusted for potential
      confounding factors. Seasonal cyclic patterns of the Campylobacter infection was
      accounted for by using sine and cosine function. Predicted probability maps
      showed a heterogeneous spatial and temporal risk of Campylobacter infection in
      Danish broiler.

PMID- 23149328
TI  - Tumor-associated stromal cells expressing E-prostanoid 2 or 3 receptors in
      prostate cancer: correlation with tumor aggressiveness and outcome by
      angiogenesis and lymphangiogenesis.
AB  - OBJECTIVE: To clarify the detailed pathologic roles of prostaglandin E(2) in
      prostate cancer tissues, the present study investigated the clinical significance
      and prognostic roles of the density of tumor-associated stromal cells expressing
      specific receptors for prostaglandin E2, termed "E-prostanoid (EP)1-4 receptors
      (EP1R-4Rs)." METHODS: The expression of each receptor was immunohistochemically
      examined in 114 formalin-fixed biopsy specimens. Correlations with
      clinicopathologic features were investigated in these specimens. Angiogenesis and
      lymphangiogenesis were measured by the percentage of CD34-stained vessels
      (microvessel density) and D2-40-stained vessels (lymph vessel density). The
      relationships between the density of each EPR-stained cells and the microvessel
      density or lymph vessel density were evaluated in 62 prostate cancer tissues
      obtained by radical surgery for more detailed analysis in a wider area of
      prostate cancer tissue. RESULTS: The density of tumor-associated cells with EP2R
      expression was positively associated with the N (P<.001) and M (P=.002) stages.
      Similarly, EP3R-positive stromal cell density was significantly associated with
      the N (P=.033) and M (P=.026) stages. The density of EP2R- and EP3R-stained cells
      correlated with the microvessel density (r=0.42, P<.001) and lymph vessel density
      (r=0.36, P=.012), respectively. A greater density of EP2R-stained cells was
      recognized as an independent predictor of progression (hazard ratio 7.26, P=.002)
      on multivariate analysis. CONCLUSION: EP2R- and EP3R-stained cells might play
      important roles in tumor progression, angiogenesis, and lymphangiogenesis in
      prostate cancer. The density of EP2R-stained stromal cells could offer a useful
      predictor of biochemical recurrence after radical surgery.

PMID- 23149329
TI  - Rectourethral fistula after salvage cryotherapy for prostate adenocarcinoma.

PMID- 23149331
TI  - Bivalirudin for primary percutaneous coronary interventions: outcome assessment
      in the Ottawa STEMI registry.
AB  - BACKGROUND: Data from randomized trials has demonstrated the superiority of
      bivalirudin to glycoprotein IIb/IIIa inhibitors plus heparin in patients
      undergoing primary percutaneous coronary intervention. Real-world performance of
      bivalirudin in primary percutaneous coronary intervention and the benefit of
      bivalirudin over heparin remain unknown in an era of routine dual antiplatelet
      therapy. METHODS AND RESULTS: From July 2004 to December 2010, 2317 consecutive
      patients were indexed in the University of Ottawa Heart Institute ST-segment
      elevation myocardial infarction registry. During this period 748 patients
      received bivalirudin, 699 patients received glycoprotein IIb/IIIa inhibitors, and
      676 patients received unfractionated heparin alone. The primary outcome was the
      rate of noncoronary artery bypass graft related thrombolysis in myocardial
      infarction major bleeding. Bivalirudin significantly reduced the primary outcome
      compared with heparin plus glycoprotein IIb/IIIa inhibitors (2.7% versus 7.3%,
      adjusted OR 2.96, 95% CI: 1.61-5.45, P<0.001) and the composite end point of
      death, stroke, reinfarction and major bleed (OR 1.66, 95% CI: 1.12-2.45, P=0.01).
      Compared with heparin alone, a reduction in major bleeds (OR 1.21, 95% CI: 0.60
      2.44, P=0.59) or the composite end point (1.05, 95% CI: 0.68-1.63, P=0.83) with
      bivalirudin could not be demonstrated. Notably, major bleeding was associated
      with a 5-fold increase in the risk of mortality both in-hospital (3.5% versus
      20.6%) and out to 180 days (5.6% versus 25.8%). CONCLUSIONS: Bivalirudin use
      compared with glycoprotein IIb/IIIa inhibitors plus heparin as an antithrombotic
      strategy in primary percutaneous coronary intervention results in less major
      bleeding in contemporary practice. A benefit of bivalirudin over heparin could
      not be established with this registry and requires additional investigations to
      either confirm or refute.

PMID- 23149332
TI  - Impact of diabetes mellitus on vessel response in the drug-eluting stent era:
      pooled volumetric intravascular ultrasound analyses.
AB  - BACKGROUND: Exaggerated neointimal hyperplasia is considered as the primary
      mechanism for increased restenosis in patients with diabetes mellitus (DM)
      treated with bare-metal stent. However, the vessel response in DM and non-DM
      treated with different drug-eluting stents (DES) has not been systematically
      evaluated. METHODS AND RESULTS: We investigated 3D intravascular ultrasound
      (postprocedure and 6 to 9 months) in 971 patients (267 with DM and 704 without
      DM) treated with sirolimus- (n=104), paclitaxel- (n=303), zotarolimus- (n=391),
      or everolimus- (n=173) eluting stents. Volumetric data were standardized by
      length as volume index (VI). At postprocedure, lumen VI at the stented segment
      was significantly smaller in DM than in non-DM, whereas vessel VI was similar
      between the 2 groups. At follow-up, neointimal obstruction and maximum cross
      sectional narrowing (neointimal area/stent area) were not significantly different
      between the 2 groups with no interaction for the DES type. Consequently, lumen VI
      was smaller in DM than in non-DM at follow-up. In the reference segments,
      residual plaque burden at postprocedure was significantly greater in DM than in
      non-DM, although change in lumen VI was similar between the 2 groups. The
      arterial responses at the reference segments also showed no interaction for the
      DES type. CONCLUSIONS: DM and non-DM lesions showed similar vessel response in
      both in-stent and reference segments regardless of the DES type. In the DES era,
      the follow-up lumen in DM patients seems to be determined primarily by the
      smaller lumen at postprocedure rather than exaggerated neointima within the stent
      or plaque proliferation at the reference segments.

PMID- 23149334
TI  - Some models just can't be fixed. A commentary on Mortensen.

PMID- 23149333
TI  - Patterns of family doctor decision making in practice context. What are the
      implications for medical practice variation and social disparities?
AB  - Medical practice variation and social disparities in health are pervasive
      features of health care systems. But what impact might everyday clinical decision
      making have in shaping such aggregate patterns, and could this in turn be
      influenced by the immediate environment in which family doctors practise? We
      investigate this by studying inter-practitioner variation in clinical activity
      across four payment types in New Zealand, a "gatekeeper" primary care system. We
      do this for four measures of clinical activity by patient ethnic and socio
      economic status in a 2001/2002 representative sample of 9272 encounters at 185
      family practices. Initial analysis showed little variation in clinical activity
      either by patient status or by practice type. However, with the application of
      multi-level statistical techniques it was evident that, while there was still
      little systematic difference in practitioner activity rates by patient status,
      inter-practitioner variation was greater for patients of ethnic minority
      background and from socio-economically deprived areas. Furthermore, this
      variability was particularly marked in fee-for-service practice settings. Thus,
      to the extent that family doctor decision-making behaviour within practice
      context helps shape aggregate patterns of medical practice variation and social
      disparity, treatment differences are likely associated not with the level of
      service but with its variability.

PMID- 23149335
TI  - Stafford breast surgeons reply to BMJ news article.

PMID- 23149336
TI  - Malignant desmoplastic infantile astrocytoma? a case report and review of the
      literature.
AB  - Desmoplastic infantile astrocytoma (DIA) and ganglioglioma (DIG) are uncommon and
      generally benign intracranial tumors that typically affect infants. Unusual cases
      bearing aggressive clinical and malignant histological features have been
      described in the literature. We report a patient who was diagnosed at the age of
      6 weeks with a DIA that relapsed 3 months postoperatively despite gross total
      resection (GTR). Pathologic examination revealed several mitoses, not only in the
      primitive neuroectodermal tumor (PNET)-like areas, but also unexpectedly in the
      predominating spindle cell component. The Ki67 proliferative index within the
      spindled component was 25%. The tumor continued to grow after initial relapse
      despite 2 courses of intensive chemotherapy (including vincristine, carboplatin,
      and temozolomide), but the recurrence was eventually controlled with oral
      etoposide. Currently, the patient is stable at 9 months after her initial
      diagnosis. This case illustrates that rare cases of DIA may display malignant
      histologic features in the typically benign and predominating spindle cell
      component and behave in an aggressive clinical manner despite GTR. As such, we
      recommend early and extended clinical follow-up of all DIA and DIG cases.

PMID- 23149337
TI  - Gs-coupled adenosine receptors differentially limit antigen-induced mast cell
      activation.
AB  - Mast cell activation results in the immediate release of proinflammatory
      mediators prestored in cytoplasmic granules, as well as initiation of lipid
      mediator production and cytokine synthesis by these resident tissue leukocytes.
      Allergen-induced mast cell activation is central to the pathogenesis of asthma
      and other allergic diseases. Presently, most pharmacological agents for the
      treatment of allergic disease target receptors for inflammatory mediators. Many
      of these mediators, such as histamine, are released by mast cells. Targeting
      pathways that limit antigen-induced mast cell activation may have greater
      therapeutic efficacy by inhibiting the synthesis and release of many
      proinflammatory mediators produced in the mast cell. In vitro studies using
      cultured human and mouse mast cells, and studies of mice lacking A(2B) receptors,
      suggest that adenosine receptors, specifically the G(s)-coupled A(2A) and A(2B)
      receptors, might provide such a target. Here, using a panel of mice lacking
      various combinations of adenosine receptors, and mast cells derived from these
      animals, we show that adenosine receptor agonists provide an effective means of
      inhibition of mast cell degranulation and induction of cytokine production both
      in vitro and in vivo. We identify A(2B) as the primary receptor limiting mast
      cell degranulation, whereas the combined activity of A(2A) and A(2B) is required
      for the inhibition of cytokine synthesis.

PMID- 23149338
TI  - Progranulin antibodies in autoimmune diseases.
AB  - Systemic vasculitides constitute a heterogeneous group of diseases. Autoimmunity
      mediated by B lymphocytes and their humoral effector mechanisms play a major role
      in ANCA-associated vasculitis (AAV) as well as in non-ANCA associated primary
      systemic vasculitides and in the different types of autoimmune connective tissue
      disorders and rheumatoid arthritis. In order to detect autoantibodies in systemic
      vasculitides, we screened protein macroarrays of human cDNA expression libraries
      with sera from patients with ANCA-associated and ANCA-negative primary systemic
      vasculitides. This approach led to the identification of antibodies against
      progranulin, a 88 kDA secreted glycoprotein with strong anti-inflammatory
      activity in the course of disease of giant-cell arteritis/polymyalgia rheumatica
      (14/65), Takayasu's arteritis (4/13), classical panarteritis nodosa (4/10),
      Behcet's disease (2/6) and in the course of disease in granulomatosis with
      polyangiitis (31/75), Churg-Strauss syndrome (7/23) and in microscopic
      polyangiitis (7/19). In extended screenings the progranulin antibodies were also
      detected in other autoimmune diseases such as systemic lupus erythematosus
      (39/91) and rheumatoid arthritis (16/44). Progranulin antibodies were detected
      only in 1 of 97 healthy controls. Anti-progranulin positive patients with
      systemic vasculitides, systemic lupus erythematosus or rheumatoid arthritis had
      significant lower progranulin plasma levels, indicating a neutralizing effect. In
      light of the anti-inflammatory effects of progranulin, progranulin antibodies
      might exert pro-inflammatory effects thus contributing to the pathogenesis of the
      respective autoimmune diseases and might serve as a marker for disease activity.
      This hypothesis is supported by the fact that a positive progranulin antibody
      status was associated with active disease in granulomatosis with polyangiitis.

PMID- 23149339
TI  - Data integration of non-animal tests for the development of a test battery to
      predict the skin sensitizing potential and potency of chemicals.
AB  - Recent changes in regulatory restrictions and social views against animal testing
      have accelerated development of reliable alternative tests for predicting skin
      sensitizing potential and potency of many chemicals. Lately, a test battery
      integrated with different in vitro tests has been suggested as a better approach
      than just one in vitro test for replacing animal tests. In this study, we created
      a dataset of 101 test chemicals with LLNA, human cell line activation test (h
      CLAT), direct peptide reactivity assay (DPRA) and in silico prediction system.
      The results of these tests were converted into scores of 0-2 and the sum of
      individual scores provided the accuracy of 85% and 71% for the potential and
      potency prediction, compared with LLNA. Likewise, the straightforward tiered
      system of h-CLAT and DPRA provided the accuracy of 86% and 73%. Additionally, the
      tiered system showed a higher sensitivity (96%) compared with h-CLAT alone,
      indicating that sensitizers would be detected with higher reliability in the
      tiered system. Our data not only demonstrates that h-CLAT can be part of a test
      battery with other methods but also supports the practical utility of a tiered
      system when h-CLAT and DPRA are the first screening methods for skin
      sensitization.

PMID- 23149340
TI  - Efficient synthesis of glycopeptide-alpha-thioesters with a high-mannose type
      oligosaccharide by means of tert-Boc-solid phase peptide synthesis.
AB  - High-mannose type oligosaccharides consist of nine mannose and two N
      acetylglucosamine residues (Man(9)GlcNAc(2):M9) and play an important role in
      protein folding processes in the endoplasmic reticulum. A highly efficient
      preparation method of this asparaginyl-M9-oligosaccharide from hen egg yolk was
      established by a two-step proteolysis with commercially available proteases and
      subsequent purification using high performance liquid chromatography (HPLC). To
      avoid the hydrolysis of the desired M9-oligosaccharide during the proteolysis
      steps, several commercially available proteases were screened for their
      contamination with mannosidases. The alpha-amino group of the resultant H(2)N-Asn
      (M9-oligosaccharide)-OH was protected with 9-fluorenylmethyloxycarbonyl (Fmoc)
      group for convenient separation by HPLC. The structure of Fmoc-Asn-(M9
      oligosaccharide)-OH thus obtained was confirmed by ESI-MS spectrometry and
      several NMR experiments. Using this Fmoc-Asn-(M9-oligosaccharide)-OH, the
      synthesis of the M9-glycopeptide-alpha-thioester was demonstrated by means of
      tert-Boc-solid phase peptide synthesis. These tert-Boc conditions afforded the M9
      glycopeptide-alpha-thioester in moderate yield.

PMID- 23149341
TI  - Tumor-line specific causes of intertumor heterogeneity in blood supply in human
      melanoma xenografts.
AB  - The efficacy of most cancer treatments is strongly influenced by the tumor blood
      supply. The results of experimental studies using xenografted tumors to evaluate
      novel cancer treatments may therefore vary considerably depending on the blood
      supply of the specific tumor model being used. Mechanisms underlying intertumor
      heterogeneity in the blood supply of xenografted tumors derived from same tumor
      line are poorly understood, and were investigated here by using intravital
      microscopy to assess tumor blood supply and vascular morphology in human
      melanomas growing in dorsal window chambers in BALB/c nu/nu mice. Two melanoma
      lines, A-07 and R-18, were included in the study. These lines differed
      substantially in angiogenic profiles. Thus, when the expression of 84
      angiogenesis-related genes was investigated with a quantitative PCR array, 25% of
      these genes showed more than a 10-fold difference in expression. Furthermore, A
      07 tumors showed higher vascular density, higher vessel tortuosity, higher vessel
      diameters, shorter vessel segments, and more chaotic vascular architecture than R
      18 tumors. Both lines showed large intertumor heterogeneity in blood supply. In
      the A-07 line, tumors with low microvascular density, long vessel segment, and
      high vessel tortuosity showed poor blood supply, whereas in the R-18 line, poor
      tumor blood supply was associated with low tumor arteriolar diameters. Thus,
      tumor-line specific causes of intertumor heterogeneity in blood supply were
      identified in human melanoma xenografts, and these tumor-line specific mechanisms
      were possibly a result of tumor-line specific angiogenic profiles.

PMID- 23149343
TI  - Strain dependence of the heat transport properties of graphene nanoribbons.
AB  - Using a combination of accurate density-functional theory and a nonequilibrium
      Green's function method, we calculate the ballistic thermal conductance
      characteristics of tensile-strained armchair (AGNR) and zigzag (ZGNR) edge
      graphene nanoribbons, with widths between 3 and 50 A. The optimized lateral
      lattice constants for AGNRs of different widths display a three-family behavior
      when the ribbons are grouped according to N modulo 3, where N represents the
      number of carbon atoms across the width of the ribbon. Two lowest-frequency out
      of-plane acoustic modes play a decisive role in increasing the thermal
      conductance of AGNR-N at low temperatures. At high temperatures the effect of
      tensile strain is to reduce the thermal conductance of AGNR-N and ZGNR-N. These
      results could be explained by the changes in force constants in the in-plane and
      out-of-plane directions with the application of strain. This fundamental
      atomistic understanding of the heat transport in graphene nanoribbons paves a way
      to effect changes in their thermal properties via strain at various temperatures.

PMID- 23149342
TI  - Membrane reconstitution of FtsZ-ZipA complex inside giant spherical vesicles made
      of E. coli lipids: large membrane dilation and analysis of membrane plasticity.
AB  - During the division process of Escherichia coli, the globular protein FtsZ is
      early recruited at the constriction site. The Z-ring, based on FtsZ filaments
      associated to the inner cell membrane, has been postulated to exert constriction
      forces. Membrane anchoring is mediated by ZipA, an essential transmembrane
      protein able to specifically bind FtsZ. In this work, an artificial complex of
      FtsZ-ZipA has been reconstituted at the inner side of spherical giant unilamellar
      vesicles made of E. coli lipids. Under these conditions, FtsZ polymerization,
      triggered when a caged GTP analogue is UV-irradiated, was followed by up to 40%
      vesicle inflation. The homogeneous membrane dilation was accompanied by the
      visualization of discrete FtsZ assemblies at the membrane. Complementary
      rheological data revealed enhanced elasticity under lateral dilation. This
      explains why vesicles can undergo large dilations in the regime of mechanical
      stability. A mechanical role for FtsZ polymers as promoters of membrane softening
      and plasticization is hypothesized.

PMID- 23149344
TI  - Restriction of LABA use to combination ICS/LABA inhaler therapy in asthma.

PMID- 23149345
TI  - Mutations in the gene phospholipase C, delta-1 (PLCD1) underlying hereditary
      leukonychia.
AB  - Hereditary leukonychia or porcelain nails is a nail dystrophy characterized by
      whitening of the nail plates in all nails of the hands and feet. It may exhibit
      an autosomal recessive or autosomal dominant pattern of inheritance. Mutations in
      the gene PLCD1 have been reported to underlie hereditary leukonychia. In the
      present study, two Pakistani families with autosomal recessive hereditary
      leukonychia were investigated. Affected members of the families exhibited
      characteristic features of hereditary leukonychia with involvement of nails on
      both the hands and feet. Genotyping using microsatellite markers linked the
      families to the gene PLCD1 on chromosome 3p22.2. Sequence analysis of the gene
      detected one novel (p.Ser740ArgfsX19) and one previously reported mutation
      (p.Arg437X). This study expands spectrum of the mutations in the gene PLCD1
      causing hereditary leukonychia.

PMID- 23149346
TI  - [Photo quiz : Superficial mycosis].

PMID- 23149347
TI  - [Photo quiz : Deep-seated mycosis].

PMID- 23149348
TI  - [Photo quiz : Basic mycology].

PMID- 23149349
TI  - [Sporotrichosis].

PMID- 23149350
TI  - [Trichosporonosis].

PMID- 23149351
TI  - [Classification of dermatophytes by mating type (MAT) gene analysis].
AB  - Trichophyton mentagrophytes is epidemiologically divided into two distinct forms,
      zoophilic and anthropophilic. The zoophilic isolates of T.mentagrophytes have
      generally been identified by morphological and biochemical examination as well as
      through mating experiments. The confirmed teleomorphs of the zoophilic isolates
      of the T.mentagrophytes complex are Arthroderma benhamiae, A. simii and A.
      vanbreuseghemii. On the other hand, no teleomorph has been identified in an
      anthropophilic isolate of T. mentagrophytes, such as T. mentagrophytes var.
      interdigitale (T. interdigitale) or in the other anthropophilic strains. In the
      present study, the mating type (MAT) (-)-specific gene of the MAT1-1 (alpha-box)
      and the MAT (+)-specific gene of the MAT1-2 (high-mobility-group : HMG) DNA
      binding domain were confirmed in zoophilic dermatophytes of A. benhamiae, A.
      simii and A. vanbreuseghemii. The sequence of the MAT1-1 was about 1.3 kbp,
      containing 2 exons in the A. benhamiae, A. simii and A. vanbreuseghemii (-)
      mating type strain. The sequence of the MAT1-2 was 1.9 kbp, containing 2 exons in
      the A. benhamiae, A. simii and A. vanbreuseghemii (+) mating type strain. Of 15
      animal isolates and 72 human isolates examined, the MAT1-1 was detected in 5 of
      the animal isolates and in none of the human isolates, while the MAT1-2 was
      detected in the other 10 of the animal isolates and in all of the human isolates.
      These results indicate that anthropophilic T. mentagrophytes evolved from the A.
      vanbreuseghemii (+) mating strain.

PMID- 23149352
TI  - [The present state of Trichophyton tonsurans infection in Japan and measures to
      combat it].
AB  - More than 10 years have passed since Trichophyton tonsurans infection first began
      to increase in Japan. Initially the infection was confined to high school and
      university students participating in combat sports clubs, but it has now spread
      among the athletes' family members and friends. In a recent survey, 10% of Judo
      athletes tested positive for Trichophyton tonsurans; most were asymptomatic
      carriers. T.tonsurans infection usually causes tinea corporis or tinea capitis,
      but lesions can occur on other sites, causing tinea unguim, tinea manus, etc .
      The course of infection is usually only mildly symptomatic, and individuals with
      long-term infection can become asymptomatic carriers. It is likely that many
      individuals are unaware that they have Trichophyton tonsurans infection. The
      number of individuals infected with clear without repeating is difficult to
      assess due to the complexity of the fungal culture process. Diagnosis is made by
      direct examination in KOH and culture, and treatment consists of topical and / or
      oral antifungals. Prevention of Trichophyton tonsurans infection through
      increased awareness of the disease and careful hygiene is important.

PMID- 23149353
TI  - [2006 Epidemiological survey of dermatomycoses in Japan].
AB  - An epidemiological survey of dermatomycoses and the causative fungus flora of
      dermatomycoses in Japan for 2006 was made on a total number of 63,029 outpatients
      who visited 16 dermatological clinics throughout Japan. The results were as
      follows. 1) Dermatophytosis was the most prevalent cutaneus fungal infection
      (7,582 cases) seen in these clinics, followed by candidiasis (842 cases) and then
      Malassezia infections (283 cases). 2) Among dermatophytoses, tinea pedis was the
      most frequent (4,779 cases : male 2,358, female 2,241), then in decreasing order,
      tinea unguium (2,582 cases : male 1,376, female 1,206), tinea corporis (564 cases
      : male 341, female 223), tinea cruris (309 cases : male 254, female 57), tinea
      manuum (145 cases : male 92, female 53), and tinea capitis including kerion (17
      cases : male 12, female 5). 3) Tinea pedis and tinea unguium are seen to increase
      in the summer season, among the aged population. When compared to the last survey
      2002 by clinical form, t. unguium patients increased 459 cases. 4) As the
      causative dermatophyte species, Trichophyton rubrum was the most frequently
      isolated among all dermatophyte infections except tinea capitis. Microsporum
      canis was slightly increased. M.gypseum and Epidermophyton floccosum are small
      number. T.tonsurans was increased up to 37 cases. 5) Cutaneous candidiasis was
      seen in 842 cases (305 male, 537 female). Intertrigo (298 cases) was the most
      frequent clinical form, followed by erosion interdigitalis (136 cases), oral
      candidiasis (135 cases), onychia et paronychia (108 cases), genital and diaper
      candidiasis in total (88 cases). 6) Tinea versicolor was seen in 175 cases.
      Malassezia folliculitis were collected 108 cases, 63 cases are reported from one
      clinic.

PMID- 23149354
TI  - Rapid identification of drug resistant Candida species causing recurrent
      vulvovaginal candidiasis.
AB  - Some yeast agents including Candida albicans, Candida tropicalis and Candida
      glabrata have a role in recurrent vulvovaginal candidiasis. We studied the
      frequency of both common and recurrent vulvovaginal candidiasis in symptomatic
      cases which were referred to Urmia Medical Sciences University related gynecology
      clinics using morphologic and molecular methods. The aim of this study was the
      identification of Candida species isolated from recurrent vulvovaginal
      candidiasis cases using a rapid and reliable molecular method. Vaginal swabs
      obtained from each case, were cultured on differential media including cornmeal
      agar and CHROM agar Candida. After 48 hours at 37C, the cultures were studied for
      growth characteristics and color production respectively. All isolates were
      identified using the molecular method of PCR - restriction fragment length
      polymorphism. Among all clinical specimens, we detected 19 ( 16 % ) non fungal
      agents, 87 ( 82.1 % ) yeasts and 2 ( 1.9 % ) multiple infections. The yeast
      isolates identified morphologically included Candida albicans ( n = 62 ), Candida
      glabrata ( n = 9 ), Candida tropicalis ( n = 8 ), Candida parapsilosis ( n = 8 )
      and Candida guilliermondii and Candida krusei ( n = 1 each ). We also obtained
      very similar results for Candida albicans, Candida glabrata and Candida
      tropicalis as the most common clinical isolates, by using PCR - Restriction
      Fragment Length Polymorphism. Use of two differential methods, morphologic and
      molecular, enabled us to identify most medically important Candida species which
      particularly cause recurrent vulvovaginal candidiasis.

PMID- 23149355
TI  - Effect of cinnamaldehyde on hyphal growth of C. albicans under various treatment
      conditions.
AB  - This study investigated the effects of cinnamaldehyde in combatting the hyphal
      growth of Candida albicans under varying concentrations, treatment times, and
      temperatures to determine the potential benefits of applying this substance to
      anti-Candida foods or gargles. From the results of pretreatment with
      cinnamaldehyde against Candida hyphae, we found that its inhibitory activity
      seemed to be strengthened in parallel with prolonged pretreatment time and a rise
      in temperature, and that pretreatment of 2,000 MUg/ml for only 1 minute
      significantly inhibited the hyphal growth of C. albicans. We also demonstrated by
      XTT assay that pretreatment with cinnamaldehyde affected the metabolic activity
      of Candida hyphal cells. These findings suggest that a warm drink or mouthwash
      containing cinnamaldehyde might be a candidate as a prophylactic or therapeutic
      tool against oral Candida infection.

PMID- 23149356
TI  - [A case of onychomycosis caused by Aspergillus sydowii].
AB  - Onychomyosis caused by Aspergillus sydowii is rare and difficult to diagnose. We
      report a case in which this disease was diagnosed by molecular-biological
      methods. The patient was a 53-year-old woman without any notable past history.
      She visited our hospital complaining of itching around the right first toenail in
      June 2010, although she had noticed nail opacification for 4 years. Opaque
      thickening of the nail, covering 57.3% of the normal nail area, was observed.
      Direct microscopic examination revealed thick mycelia with septa and black
      spores. While colonies with a red brown center and a grayish blue-green margin
      were observed in culture on Sabouraud ' s glucose agar at 25C, radially arranged
      conidia in the conidial head were observed in slide culture. Thus, onychomycosis
      caused by Aspergillus was suspected. There were no blood or biochemical test
      abnormalities. We directly extracted deoxyribonucleic acid from the nail and
      analyzed the base sequences of the internal transcribed spacer 1 and 2 regions of
      the ribosomal ribonucleic acid gene, and identified Aspergillus sydowii. Because
      the minimal inhibitory concentration of itraconazole (ITCZ) is 0.25 MUg/ml, we
      administered pulse therapy with monthly 1-week cycles of oral ITCZ 400 mg / day
      for 3 consecutive months. The opaque area subsided to 17. 9% of the normal nail
      by 6 months after treatment completion. However, 3 months later, the opaque area
      increased again to 22. 3%, and the same fungus was isolated and identified. The 3
      month ITCZ pulse therapy was repeated and the symptoms disappeared, with complete
      cure achieved by 3 months after the second therapy.

PMID- 23149357
TI  - Serum soluble CD163 levels in patients with influenza-associated encephalopathy.
AB  - BACKGROUND: Influenza-associated encephalopathy (IE) is a serious complication
      during influenza viral infection. Common clinical symptoms of IE include seizures
      and progressive coma with high-grade fever. We previously reported that
      hypercytokinemia and monocyte/macrophage activation may play an important role in
      the pathogenesis of IE. CD163 is a scavenger receptor for hemoglobin-haptoglobin
      complexes and is expressed by monocytes/macrophages. Proteolytic cleavage of
      monocyte-bound CD163 by matrix metalloproteinases releases soluble CD163
      (sCD163). However, there have been no reports regarding serum sCD163 levels in IE
      patients. METHODS: We measured serum levels of sCD163 as a marker of
      monocyte/macrophage activation in IE patients with poor outcomes, those without
      neurological sequelae, influenza patients without IE, and control subjects.
      RESULTS: Serum sCD163 levels were significantly higher in IE patients with poor
      outcomes than in those without neurological sequelae. In particular, sCD163
      levels in cases of death were significantly higher than those in other cases.
      CONCLUSIONS: Our results suggest that monocyte/macrophage activation is related
      to the pathogenesis of severe IE.

PMID- 23149358
TI  - Risk stratification in chest pain patients undergoing nuclear stress testing: the
      Erlanger Stress Score.
AB  - BACKGROUND: Studies have individually reported the relationship of age, cardiac
      risk factors, and history of preexisting coronary artery disease (CAD) for
      predicting acute coronary syndromes in chest pain patients undergoing cardiac
      stress testing. In this study, we investigate the interplay of all these factors
      on the incidence of acute coronary syndromes to develop a tool that may assist
      physicians in the selection of appropriate chest pain patients for stress
      testing. METHODS: Retrospective analysis of a prospectively acquired database of
      consecutive chest pain patients undergoing nuclear stress testing. Backward
      stepwise logistic regression was used to develop a model for predicting risk of
      30-day acute coronary events (ACE) using information obtained from age, sex,
      cardiac risk factors, and history of preexisting CAD. RESULTS: A total of 800
      chest pain patients underwent nuclear stress testing. ACE occurred in 74 patients
      (9.3%). Logistic regression analysis found only 6 factors predictive of ACE: age,
      male sex, preexisting CAD, diabetes, and hyperlipidemia. Area under the receiver
      operator characteristic curve of this model for predicting ACE was 0.767 (95%
      confidence interval, 0.719-0.815). There were no cases of ACE in the 173 patients
      with predicted probability estimates <=2.5% (95% confidence interval, 0%-2.1%).
      CONCLUSIONS: A regression model using age, sex, preexisting CAD, diabetes, and
      hyperlipidemia is predictive of 30-day ACE in chest pain patients undergoing
      nuclear stress testing. Prospective studies need to be performed to determine
      whether this model can assist physicians in the selection of appropriate low-to
      intermediate risk chest pain patients for nuclear stress testing.

PMID- 23149359
TI  - Recommendations for management of antiplatelet therapy in patients undergoing
      elective noncardiac surgery after coronary stent implantation.
AB  - Patients commonly undergo noncardiac surgical procedures after implantation of a
      coronary stent. In the case where surgery cannot be deferred until completing the
      minimum duration of dual antiplatelet therapy, the Brigham and Women's Hospital
      Cardiac Catheterization Laboratory recommends using a glycoprotein IIb/IIIa
      bridging protocol to minimize the risk of perioperative ischemic events. We
      discuss our algorithm for managing antiplatelet agents, including the newer
      agents, prasugrel and ticagrelor, in patients undergoing noncardiac surgery after
      coronary stenting and present our glycoprotein IIb/IIIa bridging strategy along
      with a review of the relevant pharmacodynamic and clinical evidence.

PMID- 23149360
TI  - Impact of the prehospital activation strategy in patients with ST-elevation
      myocardial infarction undergoing primary percutaneous revascularization: a single
      center community hospital experience.
AB  - The strategy of prehospital activation by the emergency medical system (EMS) in
      patients with ST-elevation myocardial infarction (STEMI) has been poorly adopted
      among the US hospitals that currently offer 24/7 primary percutaneous coronary
      intervention. In this study, we report a single center experience after the
      implementation of this strategy. From 2008 to 2011, we identified a total 188
      STEMI patients (age 65 +/- 15 years) presenting via EMS for primary percutaneous
      coronary intervention. Of these, 112 (59.6%) underwent prehospital activation
      (EMS group), whereas the remaining 76 (40.4%) underwent emergency department
      activation [emergency department (ED) group]. Baseline demographic
      characteristics were similar between both groups. The overall median door-to
      balloon (DTB) time was 49 +/- 14 minutes. Patients undergoing prehospital
      activation had on average significantly lower overall DTB times (EMS 44 +/- 11
      minutes vs. ED 57 +/- 15 minutes; P < 0.001). Concordantly, DTB times <60 minutes
      were much more commonly achieved with this strategy (EMS 95.5% vs. ED 64.5%; P <
      0.001). Fallouts beyond the recommended 90-minute DTB time were seen among ED
      patients only. No difference in in-hospital death (EMS 5.4% vs. ED 6.6%; P =
      0.75) or cumulative 30-day mortality (EMS 6.3% vs. ED 7.9%; P = 0.68) was
      observed between both groups. However, on average, EMS patients had higher
      postinfarct left ventricular ejection fraction (EMS 48 +/- 9.5% vs. ED 39 +/-
      14.6%; P = 0.004). Differences in DTB time and left ventricular ejection fraction
      remained significant after adjusting for differences in baseline characteristics.
      In conclusion, the prehospital activation strategy is largely effective and
      should be systematically adopted in the treatment scheme of STEMI patients to
      lower mechanical reperfusion times and reduce the potential for untoward clinical
      outcomes.

PMID- 23149361
TI  - Clinical pathway: helicopter scene STEMI protocol to facilitate long-distance
      transfer for primary PCI.
AB  - BACKGROUND: The latest American College of Cardiology/American Heart Association
      guidelines recommend primary percutaneous coronary intervention (PCI) in acute ST
      elevation myocardial infarction (STEMI) patients within 90 minutes from
      presentation to the emergency room. For interhospital transfers, the most recent
      PCI guidelines recommend first medical contact-to-device times <=120 minutes.
      Although PCI-capable hospitals have improved door-to-balloon times, many patients
      present to non-PCI-capable facilities and have been excluded from national
      quality measures. METHODS: In our acute myocardial infarction network, not only
      do we enable non-PCI hospitals to transfer STEMI patients but empower outside
      emergency medical services (EMS) to activate the catheterization laboratory team
      with a burst page and transfer STEMI patients directly from the scene. Data on
      patient characteristics, outcomes, and time elements were collected for "scene
      STEMI" patients who circumvented outlying rural non-PCI hospitals and are
      presented in this case series. RESULTS: From December 2007 to November 2010, 22
      STEMI patients with higher than average acuity were transported by helicopter
      directly to our medical center for primary PCI. Median distance from the scene to
      our medical center was 47 miles [25th to 75th interquartile range (IQR) = 39-71
      miles]. Median EMS-to-balloon time was 120 minutes (IQR = 111-134 minutes). There
      were no false activations by EMS. In comparison, our median time for
      interhospital STEMI transfers (N = 335) was 145 minutes (IQR = 121-186 minutes)
      from 2007 to 2009. CONCLUSIONS: In our single-center experience, 22 scene STEMI
      patients were diagnosed and appropriately triaged by EMS to our center for
      primary PCI. Our data show feasibility of an EMS-activated STEMI network over
      long distances with good reperfusion times.

PMID- 23149362
TI  - A novel approach to cardiac troponins to improve the diagnostic work-up in chest
      pain patients.
AB  - In patients with acute chest pain, current guidelines recommend serial
      measurements of cardiac troponins at predefined and partly late time points.
      Consequently, diagnostic assessment in these patients tends to be lengthy and
      often results in unnecessary admissions. We, therefore, evaluated whether an
      approach integrating troponin results into the clinical context provided by the
      individual patient's presentation might facilitate the early diagnostic work-up.
      In 197 chest pain patients, cardiac troponin I (cTnI; Stratus CS) was measured
      serially within 12 hours after hospital admission. In patient cohorts with
      different chances of having myocardial infarction (MI) according to clinical
      data, electrocardiographic findings, and admission biomarker results, pretest
      probabilities for MI were calculated and compared with posttest probabilities
      derived from subsequent cTnI results after admission. Elevated cTnI levels at 1
      to 2 hours after admission revealed >=95.0% posttest probabilities for MI in
      cohorts with intermediate or high chances of having MI. The posttest
      probabilities for the absence of MI were 94.7% to 98.2% in cohorts with low or
      intermediate chances of having MI when cTnI was negative at 2 hours. Troponin
      testing considering the individual patient's pretest probability of MI seems, in
      conclusion, to provide clinically useful information already 1 to 2 hours after
      admission. Such an approach has the potential to identify both patient cohorts in
      whom early discharge or admittance for further evaluation would be appropriate.
      This could facilitate the early diagnostic work-up of chest pain patients,
      thereby improving patient flow and reducing overcrowding in healthcare
      facilities.

PMID- 23149363
TI  - Chest pain unit using thrombolysis in myocardial infarction score risk
      stratification:  an impact on the length of stay and cost savings.
AB  - BACKGROUND: Despite the fact that studies have demonstrated cost-effectiveness of
      chest pain observation units (CPOUs) in emergency departments, they have not been
      widely implemented. Thrombolysis in Myocardial Infarction (TIMI) score is an easy
      and reliable tool, but none of the prior studies have used it for risk
      stratification in CPOUs. We propose to study the impact of CPOU using TIMI risk
      stratification model on the length of stay (LOS) and cost savings. METHODS: We
      studied 777 patients with chest pain admitted to our hospital from July 2010 to
      June 2011. The patients with a TIMI score of 0 to 2 were observed for 12 hours,
      those with a score of 3 to 4 were observed for 20 hours, and the ones with a
      score >4 were deemed appropriate for admission. We calculated the cost
      differences between the actual admissions and the CPOU. RESULTS: A total of 39.1%
      of patients had a TIMI score of 0, 31.1% had a TIMI score of 1, 18.1% had a TIMI
      score of 2, 9.2% and 2.5% had TIMI scores of 3 and 4, respectively. The expected
      LOS based on this model was 418.5 days versus the actual LOS of 1324 days. The
      cost of CPOU was estimated to be $1,979,977. However, the actual cost was
      $3,216,809. Hence, the annual cost savings were estimated to be $1,236,832.
      CONCLUSION: CPOU using TIMI score is an easy and reliable risk stratification
      tool for patients with chest pain in the emergency department and can
      significantly reduce the LOS, hence saving millions of dollars in this economic
      crisis.

PMID- 23149364
TI  - Ability of triage decision rules for rapid electrocardiogram to identify patients
      with suspected ST-elevation myocardial infarction.
AB  - BACKGROUND: : The American College of Cardiology/American Heart Association
      guidelines for ST-elevation myocardial infarction state that an electrocardiogram
      (ECG) should be performed on patients with suspected acute coronary syndrome upon
      presentation to the emergency department (ED) within 10 minutes. OBJECTIVE: : To
      determine how previously published clinical criteria for obtaining an ECG at ED
      triage perform in a population of patients receiving emergency cardiac
      catheterization for suspected myocardial infarction. This rule was originally
      derived by Graff to identify clinical criteria for obtaining an ECG at triage to
      rapidly identify patients with acute myocardial infarction. The Graff rule was
      developed in a setting where lytic therapy was the primary reperfusion strategy.
      A modification proposed by Glickman adds several more criteria in an effort to
      capture additional patients. We hypothesized that the Graff rule would identify
      most patients for whom the cardiac catheterization laboratory (CCL) was activated
      and that the Glickman rule would capture the remaining patients. METHODS: : Three
      trained physician reviewers retrospectively applied the Graff decision rule to
      430 consecutive patients from a database of emergency CCL activations by ED
      physicians. The Graff rule recommends that patients between the ages of 30 and 49
      years received a rapid ECG if they complained of chest pain and those aged 50
      years or older received a rapid ECG when they complained of chest pain, shortness
      of breath, palpitations, weakness, or syncope. The newly developed Glickman rule,
      which included nausea and vomiting in patients over the age of 80 years, was
      applied to the patients where the Graff rule was negative. The triage note or
      earliest medical contact documentation was used to determine whether the
      patient's complaints would have resulted in a rapid ECG by the decision rule.
      Each case was reviewed for acute myocardial infarction as defined by high-grade
      stenosis on the subsequent emergent cardiac catheterization. A single data
      collection Microsoft Excel spreadsheet was used, and descriptive statistics were
      performed in Excel and Stata. RESULTS: : Of the 430 CCL activations, 415 (97%;
      95% confidence interval, 95%-99%) were identified by the Graff rule. Of the 12
      patients who were not identified by the rule, only 2 more were identified by the
      Glickman criteria. Among patients with confirmed ST-elevation myocardial
      infarction (79% of CCL activations), the Graff rule was 98% sensitive (95%
      confidence interval, 96%-99%). CONCLUSIONS: : The Graff ECG triage rule
      identified almost all patients for whom the CCL was activated. Modification of
      the rule as proposed by Glickman added very little to the rule's sensitivity,
      while increasing the number of ECGs required at triage.

PMID- 23149365
TI  - Assessing coronary artery disease in patients with anginal chest pain and left
      bundle branch block:  an emerging role for a new parameter of cardiopulmonary
      exercise testing.
AB  - Cardiopulmonary exercise testing (CPET) is used in cardiology to grade the
      severity of heart failure and to assess its prognosis. However, it is unknown
      whether CPET may be a useful technique to rule out coronary artery disease (CAD)
      in patients with anginal chest pain and left bundle branch block (LBBB). The aim
      of this investigation was to evaluate the diagnostic accuracy of CPET to identify
      CAD in these patients. A cohort of 90 patients with anginal chest pain, 45 with
      LBBB (group A) and 45 non-LBBB (group B), were studied with CPET and a single
      photon emission computed tomographic myocardial perfusion study during the same
      period. The following variables of CPET were analyzed: peak oxygen uptake (VO2),
      VO2 at anaerobic threshold, and time to reach the anaerobic threshold (TAT).
      Group A values were lower compared with group B in peak VO2 (23 +/- 6.2 vs. 28 +/
      7.6 mLO2 . kg . min; P = 0.002), VO2 at anaerobic threshold (16.1 +/- 3.6 vs.
      18.9 +/- 4.1 mLO2 . kg . min; P =0.001), and TAT (2.7 +/- 0.96 vs. 4.4 +/- 2.1
      min; P < 0.001). Group A showed higher perfusion abnormalities in myocardial
      perfusion study than group B [27 (60%) vs. 12 (26.7%); P = 0.003]. Multivariate
      analysis showed that TAT (odds ratio = 1.59; 95% confidence interval, 1.06-2.39;
      P = 0.02) was the only independent predictor of CAD, after controlling for other
      factors. Receiver operator characteristic analysis showed an area under the curve
      of 0.78 for TAT (95% confidence interval, 0.68-0.86; P < 0.0001). In conclusion,
      our findings suggest that a new functional parameter such as TAT significantly
      predicts CAD in patients with anginal chest pain and LBBB.

PMID- 23149366
TI  - Electrocardiogram with a twist.
AB  - This report presents a 55-year-old man admitted for respiratory failure, who was
      found to have a brief run of polymorphic ventricular tachycardia (PVT) with
      normal QT interval. The importance of differentiating PVT caused by torsades de
      pointes and PVT with normal QT interval is emphasized. This distinction is
      crucial because of the differing etiologies and management of these arrhythmias.

PMID- 23149367
TI  - Association between oral fluoroquinolones and retinal detachment.

PMID- 23149369
TI  - Real-time polymerase chain reaction in the diagnosis of acute postoperative
      endophthalmitis.

PMID- 23149370
TI  - Anti-inflammatory effect of low-molecular-weight heparin in pediatric cataract
      surgery.

PMID- 23149372
TI  - Cataract surgery in eyes with nanophthalmos and relative anterior microphthalmos.

PMID- 23149374
TI  - Diplomorphanins A and B: new C-methyl flavonoids from Diplomorpha canescens.
AB  - Two new C-methyl flavonoids, diplomorphanins A (1) and B (2) were isolated from
      the aerial parts of Diplomorpha canescens (MEISN.) C. A. MEYER along with a known
      compound, farrerol 7-O-beta-D-glucopyranoside (3). Structures of these compounds
      were determined on the basis of spectroscopic data.

PMID- 23149375
TI  - Molecular beam mass spectrometry with tunable vacuum ultraviolet (VUV)
      synchrotron radiation.
AB  - Tunable soft ionization coupled to mass spectroscopy is a powerful method to
      investigate isolated molecules, complexes and clusters and their spectroscopy and
      dynamics(1-4). Fundamental studies of photoionization processes of biomolecules
      provide information about the electronic structure of these systems. Furthermore
      determinations of ionization energies and other properties of biomolecules in the
      gas phase are not trivial, and these experiments provide a platform to generate
      these data. We have developed a thermal vaporization technique coupled with
      supersonic molecular beams that provides a gentle way to transport these species
      into the gas phase. Judicious combination of source gas and temperature allows
      for formation of dimers and higher clusters of the DNA bases. The focus of this
      particular work is on the effects of non-covalent interactions, i.e., hydrogen
      bonding, stacking, and electrostatic interactions, on the ionization energies and
      proton transfer of individual biomolecules, their complexes and upon micro
      hydration by water(1, 5-9). We have performed experimental and theoretical
      characterization of the photoionization dynamics of gas-phase uracil and 1,3
      dimethyluracil dimers using molecular beams coupled with synchrotron radiation at
      the Chemical Dynamics Beamline(10) located at the Advanced Light Source and the
      experimental details are visualized here. This allowed us to observe the proton
      transfer in 1,3-dimethyluracil dimers, a system with pi stacking geometry and
      with no hydrogen bonds(1). Molecular beams provide a very convenient and
      efficient way to isolate the sample of interest from environmental perturbations
      which in return allows accurate comparison with electronic structure
      calculations(11, 12). By tuning the photon energy from the synchrotron, a
      photoionization efficiency (PIE) curve can be plotted which informs us about the
      cationic electronic states. These values can then be compared to theoretical
      models and calculations and in turn, explain in detail the electronic structure
      and dynamics of the investigated species (1, 3).

PMID- 23149377
TI  - Paediatric lymphoma in China:  a clinicopathological study of 213 cases.
AB  - AIM: This retrospective study was conducted to evaluate information on paediatric
      lymphoma in China. METHODS: We reviewed the pathological files of patients less
      than 12 years of age with lymphoma in Shanghai Xinhua Hospital from January 1982
      to June 2009. SPSS version 11.0 was used to analyse the results. RESULTS: Of the
      213 subjects, 176 (82.6%) had non-Hodgkin's lymphoma (NHL) and 37 (17.4%) had
      Hodgkin's lymphoma (HL). All NHL cases had diffuse and high grade tumours, and
      33.5% of these tumours primarily involved extra-nodal sites. Of the NHL cases,
      56.6%, 43.3%, and 1.7% were derived from T, B, and null cells, respectively.
      Lymphoblastic lymphoma (LL, 50.6%), Burkitt's lymphoma (BL, 28.4%), and
      anaplastic large cell lymphoma (ALCL, 12.5%) comprised the majority of the NHL
      cases. A significant difference was found in the frequency of stage I/II cases
      between LL and ALCL. Paediatric HL resembled the disease in adults. CONCLUSIONS:
      Paediatric lymphoma in China is different from that in Western countries with
      respect to the incidence rate of HL and BL. The distribution pattern of NHL
      histological subtypes is more similar to that in Japan than that in Pakistan.
      These features suggest ethnic or geographic variations.

PMID- 23149376
TI  - Attempted suicide with liraglutide overdose did not induce hypoglycemia.
AB  - We document the first reported case of attempted suicide with the GLP-1 receptor
      agonist, liraglutide: a 33-year-old Japanese woman with type 2 diabetes reported
      subcutaneously injected 72 mg of liraglutide. She experienced gastrointestinal
      symptoms but no hypoglycemia.

PMID- 23149378
TI  - Immunohistochemical expression and prognostic significance of oestrogen receptor
      alpha, oestrogen receptor-beta, and progesterone receptor in stage 1 adult-type
      granulosa cell tumour of the ovary.
AB  - AIMS: To assess oestrogen receptor (ER)alpha, ERbeta, and progesterone receptor
      (PR) expression in stage I ovarian adult-type granulosa cell tumours (AGCTs) and
      correlate the findings with clinical outcome. METHODS: ERalpha, ERbeta and PR
      immunohistochemistry was performed on 56 primary, stage I AGCTs. Twelve cases
      (21%) recurred and hormone receptor staining was compared in the corresponding
      primary and metastatic tumours. RESULTS: All primary AGCTs expressed ERbeta and
      PR, usually with strong and diffuse staining, whereas only 20% of tumours were
      focally ERalpha positive. There was no correlation between ERalpha or PR
      expression and outcome. However, primary AGCTs with low ERbeta expression had a
      significantly higher risk of recurrence. In contrast, all metastatic tumours
      exhibited strong ERbeta staining. No relationship between ER staining and tumour
      morphology was identified but there was more consistent PR expression in cells at
      the tumour-stromal interface. CONCLUSIONS: Primary AGCTs typically show an
      ERalpha negative and ERbeta/PR positive immunophenotype. Low ERbeta expression is
      an adverse prognostic factor in primary AGCT but metastatic tumours often show up
      regulation of ERbeta. Local microenvironmental factors may influence PR
      expression. Hormone receptor expression in AGCT may become increasingly relevant
      due to developments in selective therapy.

PMID- 23149379
TI  - Benchmarking in pathology:  development of an activity-based costing model.
AB  - AIMS: Benchmarking in Pathology (BiP) allows pathology laboratories to determine
      the unit cost of all laboratory tests and procedures, and also provides
      organisational productivity indices allowing comparisons of performance with
      other BiP participants. We describe 14 years of progressive enhancement to a BiP
      program, including the implementation of 'avoidable costs' as the accounting
      basis for allocation of costs rather than previous approaches using 'total
      costs'. METHODS: A hierarchical tree-structured activity-based costing model
      distributes 'avoidable costs' attributable to the pathology activities component
      of a pathology laboratory operation. The hierarchical tree model permits costs to
      be allocated across multiple laboratory sites and organisational structures. This
      has enabled benchmarking on a number of levels, including test profiles and non
      testing related workload activities. The development of methods for dealing with
      variable cost inputs, allocation of indirect costs using imputation techniques,
      panels of tests, and blood-bank record keeping, have been successfully integrated
      into the costing model. RESULTS: A variety of laboratory management reports are
      produced, including the 'cost per test' of each pathology 'test' output.
      Benchmarking comparisons may be undertaken at any and all of the 'cost per test'
      and 'cost per Benchmarking Complexity Unit' level, 'discipline/department' (sub
      specialty) level, or overall laboratory/site and organisational levels.
      CONCLUSIONS: We have completed development of a national BiP program. An activity
      based costing methodology based on avoidable costs overcomes many problems of
      previous benchmarking studies based on total costs. The use of benchmarking
      complexity adjustment permits correction for varying test-mix and diagnostic
      complexity between laboratories. Use of iterative communication strategies with
      program participants can overcome many obstacles and lead to innovations.

PMID- 23149380
TI  - Speech dominance is a better predictor of functional brain asymmetry than
      handedness: a combined fMRI word generation and behavioral dichotic listening
      study.
AB  - An unresolved issue in behavioral studies of hemispheric asymmetry is why both
      left-handers and right-handers show a right ear advantage at the group level. In
      the present study we screened left-handers for left- versus right-hemisphere
      speech dominance with fMRI by comparing right versus left hemisphere frontal lobe
      activity (in Broca's area) in a silent word generation task. A left hemisphere
      dominant right-handed control group was included as well. All participants took
      part in a dichotic listening task with consonant-vowel syllables. The results
      showed that left-handers and right-handers with left-hemisphere speech dominance
      showed a right ear advantage. However, the left-handers with right hemisphere
      speech dominance had a left ear advantage. Thus, at the group level the direction
      of the ear advantage in dichotic listening was predicted by language dominance
      but not by hand preference. At the individual level, the dichotic task we used
      showed more variability than the fMRI results. Further research will have to
      indicate whether this is a feature inherent to dichotic listening, or whether the
      variability is due to alternative explanations such as a more bilateral
      representation of speech perception compared to speech production.

PMID- 23149381
TI  - New NHS Constitution could cause conflict with professional guidance on patient
      confidentiality and the Mental Capacity Act.

PMID- 23149382
TI  - Screening for severe physical inactivity in chronic obstructive pulmonary
      disease: the value of simple measures and the validation of two physical activity
      questionnaires.
AB  - Objectively measured severe physical inactivity (SPI) has been reported as the
      strongest independent predictor of mortality in patients with chronic obstructive
      pulmonary disease (COPD). Activity monitoring is not feasible in routine clinical
      practice; therefore, we set out to determine the utility of simple clinical
      measures for predicting SPI in patients with COPD. A total of 165 patients with
      COPD wore an activity monitor for 5 days to define the presence or absence of
      SPI. Logistic models were generated including the modified Medical Research
      Council (MMRC) dyspnea grade, spirometry and the age-dyspnea-airflow obstruction
      (ADO) index. Physical Activity Scale for the Elderly (PASE) and Stanford Brief
      Activity Scale (SBAS) were also tested for validity and reliability in a subgroup
      of 67 patients. The MMRC dyspnea grade, PASE score, ADO index and SBAS score were
      associated with SPI, but general self-efficacy and spirometry were not. An MMRC
      dyspnea grade >=3 was the best independent predictor of SPI (AUC: 0.74; PPV:
      0.83; NPV: 0.68) followed closely by a PASE score of <111. The combination of
      MMRC dyspnea grade and PASE score provided the most robust model (AUC: 0.83;
      Positive Predictive Value (PPV): 0.95; Negative Predictive Value (NPV): 0.63).
      The results were confirmed using 5000 bootstrapped models from the cohort of 165
      patients. MMRC dyspnea grade >=3 may be the best triage tool for SPI in patients
      with COPD. The combination of the MMRC and PASE score provided the most robust
      prediction. Our results may have significant practical applicability for
      clinicians caring for patients with COPD.

PMID- 23149383
TI  - Volitional pursed lips breathing in patients with stable chronic obstructive
      pulmonary disease improves exercise capacity.
AB  - Pursed lips breathing (PLB) is used by a proportion of patients with chronic
      obstructive pulmonary disease (COPD) to alleviate dyspnea. It is also commonly
      used in pulmonary rehabilitation. Data to support its use in patients who do not
      spontaneously adopt PLB are limited. We performed this study to assess the acute
      effects of PLB on exercise capacity in nonspontaneously PLB patients with stable
      COPD. We performed a randomized crossover study comparing 6-min walk test (6MWT)
      at baseline without PLB with 6WMT using volitional PLB. Spirometry, maximal
      inspiratory and expiratory mouth pressures, and diaphragmatic excursion during
      tidal and vital capacity breathing using B-mode ultrasonography were measured at
      baseline and after 10 min of PLB. A Visual Analog Scale (VAS) assessed subjective
      breathlessness at rest, after 6MWT and after 6MWT with PLB. p <= 0.01 was
      considered significant. Mean +/- SD age of patients was 53.1 +/- 7.4 years.
      Forced expiratory volume in 1 second was 1.1 +/- 0.4 L/min (38.4 +/- 13.2%
      predicted). Compared with spontaneous breathing, all but one patient with PLB
      showed a significant increment in 6MW distance (+34.9 +/- 26.4 m; p = 0.002).
      There was a significant reduction in respiratory rate post 6MWT with PLB compared
      with spontaneous breathing (-4.4 +/- 2.8 per minute; p = 0.003). There was no
      difference in VAS scores. There was a significant correlation between improvement
      in 6MWT distance and increase in diaphragmatic excursion during forced breathing.
      The improvement was greater in patients who had poorer baseline exercise
      performance. PLB has an acute benefit on exercise capacity. Sustained PLB or
      short bursts of PLB may improve exercise capacity in stable COPD.

PMID- 23149384
TI  - Factors associated with early adherence to tiotropium in chronic obstructive
      pulmonary disease.
AB  - Tiotropium is an innovative intervention in chronic obstructive pulmonary disease
      (COPD). Early adherence to tiotropium remains inadequately explored, notably time
      from initiation to discontinuation (persistence). In patients with COPD, the
      factors associated with the risk of discontinuing the treatment with tiotropium
      within 12 months following initiation were identified (12-month persistence).
      Claim databases from the French Social Security were used. A random sample of
      patients (aged 50-80 years) who initiated tiotropium soon after launch was
      selected. Factors associated with the persistence were investigated (Log-rank
      test and multivariate Cox model). Of the 1147 newly treated patients (mean age 68
      years, 33% women), 64% remained in the treatment of tiotropium for over a period
      of 12 months following initiation. More than 10% of the patients interrupted
      therapy after a single dispensing, most often those with mild COPD. Lower risks
      of discontinuing tiotropium within 12 months following initiation were observed
      when it was initiated by a private sector specialist (hazard ratio (HR) = 0.65,
      95% confidence interval (CI) = (0.52-0.82)), by hospital-based physician (HR =
      0.58, 95% CI = (0.42-0.78)), when >= 2 other respiratory drugs were associated
      (HR = 0.74, 95% CI = (0.58-0.95)) and in case of long-term disease status (HR =
      0.78, 95% CI = (0.63-0.97)). Conversely, no clear effect appeared according to
      age or gender. In this population of patients with COPD, fewer early
      discontinuations of tiotropium were observed in patients having a severe
      condition.

PMID- 23149386
TI  - Distinct signalling pathways control Toxoplasma egress and host-cell invasion.
AB  - Calcium signalling coordinates motility, cell invasion, and egress by
      apicomplexan parasites, yet the key mediators that transduce these signals remain
      largely unknown. One underlying assumption is that invasion into and egress from
      the host cell depend on highly similar systems to initiate motility. Using a
      chemical-genetic approach to specifically inhibit select calcium-dependent
      kinases (CDPKs), we instead demonstrate that these pathways are controlled by
      different kinases: both TgCDPK1 and TgCDPK3 were required during ionophore
      induced egress, but only TgCDPK1 was required during invasion. Similarly,
      microneme secretion, which is necessary for motility during both invasion and
      egress, universally depended on TgCDPK1, but only exhibited TgCDPK3 dependence
      when triggered by certain stimuli. We also demonstrate that egress likely comes
      under a further level of control by cyclic GMP-dependent protein kinase and that
      its activation can induce egress and partially compensate for the inhibition of
      TgCDPK3. These results demonstrate that separate signalling pathways are
      integrated to regulate motility in response to the different signals that promote
      invasion or egress during infection by Toxoplasma gondii.

PMID- 23149387
TI  - Extracellular matrix degradation in liver fibrosis: Biochemistry and regulation.
AB  - Fibrosis is a highly conserved wound healing response and represents the final
      common pathway of virtually all chronic inflammatory injuries. Over the past 3
      decades detailed analysis of hepatic extracellular matrix synthesis and
      degradation using approaches incorporating human disease, experimental animal
      models and cell culture have highlighted the extraordinarily dynamic nature of
      tissue repair and remodelling in this solid organ. Furthermore emerging studies
      of fibrosis in other organs demonstrate that basic common mechanisms exist,
      suggesting that bidirectionality of the fibrotic process may not solely be the
      preserve of the liver. In this review we will examine the cellular and molecular
      mechanisms that govern extracellular matrix degradation and fibrosis resolution,
      and highlight how manipulation of these processes may result in the development
      of effective anti-fibrotic therapies. This article is part of a Special Issue
      entitled: Fibrosis: Translation of basic research to human disease.

PMID- 23149385
TI  - OXPHOS mutations and neurodegeneration.
AB  - Mitochondrial oxidative phosphorylation (OXPHOS) sustains organelle function and
      plays a central role in cellular energy metabolism. The OXPHOS system consists of
      5 multisubunit complexes (CI-CV) that are built up of 92 different structural
      proteins encoded by the nuclear (nDNA) and mitochondrial DNA (mtDNA). Biogenesis
      of a functional OXPHOS system further requires the assistance of nDNA-encoded
      OXPHOS assembly factors, of which 35 are currently identified. In humans,
      mutations in both structural and assembly genes and in genes involved in mtDNA
      maintenance, replication, transcription, and translation induce 'primary' OXPHOS
      disorders that are associated with neurodegenerative diseases including Leigh
      syndrome (LS), which is probably the most classical OXPHOS disease during early
      childhood. Here, we present the current insights regarding function, biogenesis,
      regulation, and supramolecular architecture of the OXPHOS system, as well as its
      genetic origin. Next, we provide an inventory of OXPHOS structural and assembly
      genes which, when mutated, induce human neurodegenerative disorders. Finally, we
      discuss the consequences of mutations in OXPHOS structural and assembly genes at
      the single cell level and how this information has advanced our understanding of
      the role of OXPHOS dysfunction in neurodegeneration.

PMID- 23149389
TI  - Pediatric thyroid disease: when is surgery necessary, and who should be operating
      on our children?
AB  - Surgical diseases of the thyroid in the pediatric population represent a diverse
      set of both benign and malignant conditions. Overall, incidence is rare. Benign
      conditions include Graves' disease, toxic adenomas, congenital hyperthyroidism,
      and goiter. Differentiated thyroid cancer (DTC) and medullary thyroid carcinoma
      (MTC), with its related familial cancer syndromes, are the most common
      malignancies. Near-total or total thyroidectomy is the appropriate surgery for
      thyroid cancer, with/out central lymph node dissection. Emerging practice
      guidelines from professional societies are helpful, although they generally have
      not addressed surgical management of the pediatric patient. Thyroidectomy in
      children is associated with a higher rate of complications, such as recurrent
      laryngeal nerve injury and hypoparathyroidism, as compared to the surgery in
      adults. Therefore, it is essential that pediatric thyroidectomy be performed by
      high-volume thyroid surgeons, regardless of specialty. Case volume to support
      surgical expertise usually must be borrowed from the adult experience, given the
      relative paucity of pediatric thyroidectomies at an institutional level. These
      surgeons should work as part of a multidisciplinary team that includes pediatric
      endocrinologists and anesthesiologists, pediatricians, nuclear medicine
      physicians, and pathologists to afford children the best clinical outcomes.

PMID- 23149390
TI  - Thyroid function in small for gestational age newborns: a review.
AB  - Several studies have shown that small for gestational age (SGA) babies have a
      different hormonal profile than those born with a birth weight appropriate for
      gestational age (AGA). Thyroid hormones play an important role in growth and
      neurocognitive development. Only few studies analyzed the concentrations of
      thyroid-stimulating hormone (TSH) and thyroxine (T4) during fetal and
      extrauterine life in SGA and AGA newborns, and the existing data on the possible
      alterations of these hormones in postnatal life are controversial. It remains to
      be established whether SGA newborns have different blood concentrations of
      thyroid hormones as compared with AGA infants and if so, whether these findings
      play a role in the development of obesity, short stature, hypertension, and
      diabetes--disorders, already known to be related with SGA birth. It has also not
      yet been established whether and when substitutive therapy with levothyroxine
      (LT4) should be initiated in preterm and full-term SGA newborns. Further trials
      are needed to determine the thyroid hormone profile in both preterm and full-term
      SGA newborns and also to evaluate the effectiveness and safety of LT4 treatment
      in these infants.

PMID- 23149391
TI  - Thyroid function and obesity.
AB  - Nowadays, childhood obesity is one of the biggest health emergencies in the
      developed countries. Obesity leads to multiple metabolic alterations which
      increase the risk of developing diabetes and cardiovascular diseases. Thyroid
      function has been often described as altered in obese children, however, it is
      not clear whether the altered thyroid function is the cause or the consequence of
      fat excess. On the other hand, thyroid structure seems also to be affected.
      Nevertheless, both functional and structural alterations seem to improve after
      weight loss and therefore no treatment is needed.

PMID- 23149388
TI  - Comparison of the clinical expression of patients with ankylosing spondylitis
      from Europe and Latin America.
AB  - OBJECTIVE: To compare the clinical, demographic, and serologic characteristics
      and the treatment of patients diagnosed with ankylosing spondylitis (AS) from
      Europe (EU) and Latin America (LA). METHODS: We included 3439 patients from
      national registries: the Spanish Registry of Spondyloarthritis (REGISPONSER), the
      Belgian registry (ASPECT), and the Latin American Registry of
      Spondyloarthropathies (RESPONDIA). We selected patients with diagnosis of AS who
      met the modified New York classification criteria. Demographic, clinical, disease
      activity, functional, and metrological measurement data were recorded. Current
      treatment was recorded. The population was classified into 2 groups: patients
      with disease duration < 10 years and those with disease duration >= 10 years. A
      descriptive and comparative analysis of variables of both groups was carried out.
      RESULTS: There were 2356 patients in EU group and 1083 in LA group. Prevalence of
      HLA-B27 was 71% in LA group and 83% in EU group (p < 0.001). We found a greater
      frequency of peripheral arthritis and enthesitis (p < 0.001) in the LA
      population; prevalence of arthritis was 57% in LA and 42% in EU, and for
      enthesitis, 54% and 38%. Except for treatment with anti-tumor necrosis factor
      (anti-TNF), the use of nonsteroidal antiinflammatory drugs (NSAID),
      corticosteroids, and disease-modifying antirheumatic drugs (DMARD), and the
      association of anti-TNF and methotrexate use showed a significant difference (p <
      0.001) in the 2 populations. CONCLUSION: The principal differences in the
      clinical manifestations of patients with AS from EU and LA were the greater
      frequency of peripheral arthritis and enthesitis in LA group, the higher
      percentage of HLA-B27 in EU group, and the form of treatment, with a greater use
      of NSAID, steroids, and DMARD in the LA group.

PMID- 23149392
TI  - Applied peritoneal anatomy.
AB  - The peritoneal cavity is a complex anatomical structure with multiple attachments
      and connections. These are better understood with reference to the embryological
      development of this region. Armed with this knowledge, the diagnosis and
      assessment of a wide range of common intra-abdominal diseases becomes
      straightforward. This article will review and simplify the terminology, complex
      embryological development, and anatomy of the peritoneum, peritoneal attachments,
      and the reflections forming the peritoneal boundaries. Normal anatomy will be
      described using schematic diagrams with corresponding computed tomography (CT)
      and magnetic resonance imaging (MRI) images, including CT peritoneograms. The
      relevance of intra- and extra-peritoneal anatomy to common pathological processes
      will be demonstrated.

PMID- 23149393
TI  - Ethnic differences in physical pain sensitivity: role of acculturation.
AB  - Although research suggests that Asian Americans are more reactive to physical
      pain than European Americans, some evidence suggests that the observed
      differences in ethnicity may actually reflect Asian Americans' differing levels
      of acculturation. Two studies were conducted to test this hypothesis. In Study 1,
      first- and second-generation Asian Americans and European Americans took part in
      a cold pressor task. Evidence of heightened pain responses was found only among
      first-generation Asian Americans. Study 2 further controlled for ethnicity and
      replicated this pattern in finding heightened pain reactions among mainland
      Chinese students in Hong Kong relative to Hong Kong Chinese students. These
      findings suggest a role for acculturation in accounting for ethnic differences in
      physical pain sensitivity.

PMID- 23149394
TI  - Tribological behavior of a charged atomic force microscope tip on graphene oxide
      films.
AB  - The tribological behavior of graphene oxide (GO) films deposited on a mica
      substrate has been investigated by atomic force microscopy, in which different
      voltages were applied to a tip. It was found that the frictional forces on the GO
      films remain unchanged in the presence of negative tip voltages, while the
      frictional forces increase remarkably with an increase of the voltage when
      positive voltages are given to the tip, and at a certain positive tip voltage the
      frictional forces reach a stable value with increasing number of repeated cycles.
      To study the influence of the tip voltage on the frictional forces of the GO
      films, the adhesive and electrostatic force gradients between the tip and GO
      films were measured. The results showed that the adhesive and electrostatic
      forces increased with increase of the positive tip voltages. This phenomenon is
      due to the polarization of charges in the GO films induced by the applied tip
      voltages, which causes intensive electrostatic interactions between the tip and
      GO films and a corresponding rise in the adhesive forces and the frictional
      forces.

PMID- 23149395
TI  - The contrasting roles of growth traits and architectural traits in diversity
      maintenance in clonal plant communities.
AB  - Plant communities often exhibit high diversity, even though pairwise experiments
      usually result in competitive hierarchies that should result in competitive
      exclusion. Such experiments, however, do not typically allow expression of
      spatial traits, despite theoretical studies showing the potential importance of
      spatial mechanisms of diversity maintenance. Here we ask whether, in a clonal
      plant model system, spatial trait variation is more likely than growth trait
      variation to maintain diversity. We used a field-calibrated, spatially explicit
      model to simulate communities comprising sets of four simulated species differing
      in only one of a suite of architectural or growth traits at a time, examining
      their dynamics and long-term diversity. To compare trait manipulation effects
      across traits measured in different units, we scaled traits to have identical
      effects on initial productivity. We found that in communities of species
      differing only in an architectural trait, all species usually persist, whereas
      communities of species differing only in a growth trait experienced rapid
      competitive exclusion. To examine the roles of equalizing and stabilizing
      mechanisms in maintaining diversity, we conducted reciprocal invasion experiments
      for species pairs differing only in single traits. The results suggest that
      stabilizing mechanisms cannot account for the observed long-term co-occurrence.
      Strong positive correlations between diversity and similarity both in monoculture
      carrying capacity and reciprocal invasion ability suggesting equalizing
      mechanisms may instead be responsible.

PMID- 23149396
TI  - Models of experimental competitive intensities predict home and away differences
      in invasive impact and the effects of an endophytic mutualist.
AB  - Understanding the role of competition in the organization of communities is
      limited in part by the difficulty of extrapolating the outcomes of small-scale
      experiments to how such outcomes might affect the distribution and abundance of
      species. We modeled the community-level outcomes of competition, using
      experimentally derived competitive effects and responses between an exotic
      invasive plant, Centaurea stoebe, and species from both its native and nonnative
      ranges and using changes in these effects and responses elicited by
      experimentally establishing symbioses between C. stoebe and fungal endophytes.
      Using relative interaction intensities (RIIs) and holding other life-history
      factors constant, individual-based and spatially explicit models predicted
      competitive exclusion of all but one North American species but none of the
      European species, regardless of the endophyte status of C. stoebe. Concomitantly,
      C. stoebe was eliminated from the models with European natives but was codominant
      in models with North American natives. Endophyte symbiosis predicted increased
      dominance of C. stoebe in North American communities but not in European
      communities. However, when experimental variation was included, some of the model
      outcomes changed slightly. Our results are consistent with the idea that the
      effects of competitive intensity and mutualisms measured at small scales have the
      potential to play important roles in determining the larger-scale outcomes of
      invasion and that the stabilizing indirect effects of competition may promote
      species coexistence.

PMID- 23149397
TI  - Use of alpha, beta, and gamma diversity measures to characterize seed dispersal
      by animals.
AB  - Seed dispersal shapes ecological and evolutionary dynamics of plant populations.
      Here, we extend classical diversity measures to study the impact of disperser
      behavior on seed dispersal. We begin by extending our previous diversity
      structure approach, which partitioned seed source diversity within and among
      dispersal sites, into the more general framework of traditional diversity
      measures. This statistical approach allows an assessment of the extent to which
      foraging behavior shapes alpha and gamma diversity, as well as the divergence in
      seed sources among dispersal sites, which we call delta. We also introduce tests
      to facilitate comparisons of diversity among dispersal sites and seed vectors and
      to compare overall diversity among sampled systems. We then apply these tools to
      investigate the diversity blend of parentage resulting from seed dispersal by two
      avian seed vectors with very different social and foraging behaviors: (1) acorn
      woodpeckers, transporting Quercus agrifolia acorns, and (2) long-wattled
      umbrellabirds, transporting Oenocarpus bataua palm nuts. Using these diversity
      and divergence measures, we test the hypothesis that different foraging behaviors
      generate distinctive diversity partitions for the two focal tree species. This
      approach provides a new tool for assessment of the impact of dispersal agents on
      the seed source structure of plant populations, which can be extended to include
      the impact of virtually any propagule vector for a range of systems.

PMID- 23149398
TI  - A treefrog with reproductive mode plasticity reveals a changing balance of
      selection for nonaquatic egg laying.
AB  - Nonaquatic reproduction has evolved repeatedly, but the factors that select for
      laying eggs on land are not well understood. The treefrog Dendropsophus
      ebraccatus has plasticity in its reproductive mode, laying eggs that successfully
      develop in or out of water. This permits the first experimental comparison of the
      selective agents that shape adult oviposition behavior and embryo developmental
      capacity. I quantified the sources and strengths of arboreal and aquatic egg
      mortality and how mortality varies with weather patterns, and I assessed 39 years
      of daily rainfall patterns to infer historic levels of egg mortality and effects
      of climate change on the selective balance between aquatic and nonaquatic egg
      deposition. Aquatic predators and desiccation were the strongest selective agents
      in water and air, respectively. Egg mortality varied with weather such that
      aquatic oviposition was advantageous when rainfall was low but laying eggs out of
      water increased survival when rainfall was high. Additionally, I found that since
      1972 there have been significant changes in the rainfall patterns in central
      Panama, and this has altered the selective landscape acting on egg-laying
      behavior. This work provides insight into the evolution and maintenance of
      adaptive phenotypic plasticity as well as historic and current selection on
      reproduction.

PMID- 23149399
TI  - Short-lived ants take greater risks during food collection.
AB  - Life-history theory predicts that organisms should alter their behavior if life
      expectancy declines. Recent theoretical work has focused on worker life
      expectancy as an ultimate factor in allocating risk-related tasks among the
      workforce in social insects. A key prediction of this evolutionary model is that
      workers with shorter life expectancy should perform riskier tasks. We tested this
      hypothesis, using laboratory colonies of the ant Myrmica scabrinodis. We modified
      foraging so that it differed in level of risk by manipulating distances,
      temperatures, and the presence of competitors on foraging patches. The life
      expectancies of foragers were shortened by poisoning with carbon dioxide or by
      injury through removal of their propodeal spines. Both treatments significantly
      shortened worker life expectancy in comparison with untreated ants. We show, for
      the first time, that foragers with a shorter life expectancy foraged under risk
      more often than foragers in the control group. Thus, a worker's strategy of
      foraging under risky circumstances appears to be fine-tuned to its life
      expectancy.

PMID- 23149400
TI  - How reliable is song learning accuracy as a signal of male early condition?
AB  - That many species of songbirds learn their songs imitatively is well established,
      but it is less clear why they do so. A component of the developmental-stress
      hypothesis posits that young males in good condition learn songs more accurately
      than males in poor condition and that females use learning accuracy as an honest
      signal of male developmental history. An unresolved problem is how females
      reliably assess learning accuracy when they are not certain of the identity of
      the male's tutor and thus the specific model from which a song was copied. We
      therefore investigated whether song learning accuracy assessment (SLAA) can be
      reliable, using evolutionary simulation models of song learning. We found that
      SLAA is indeed less reliable than assessment in which male signals are compared
      to an unlearned standard, as a result of three types of errors in matching songs
      to their models. In the simplest models, SLAA was particularly unreliable, but
      when the model is made more realistic by including features such as
      geographically constrained learning, repertoire complexity, and, in particular,
      song categorization, the reliability of SLAA increased. Our results demonstrate a
      range of conditions under which the assessment of song learning accuracy might be
      reasonably reliable and therefore likely to evolve.

PMID- 23149401
TI  - A quantitative test of the predicted relationship between countershading and
      lighting environment.
AB  - Countershading, a vertical luminance gradient from a dark back to a light belly,
      is perhaps the most common coloration phenotype in the animal kingdom. Why? We
      investigated whether countershading functions as self-shadow concealment (SSC) in
      ruminants. We calculated "optimal" countershading for SSC by measuring
      illumination falling onto a model ruminant as a function of time of day and
      lighting environment. Calibrated images of 114 species of ruminant were compared
      to the countershading model, and phylogenetic analyses were used to find the best
      predictors of coats' countershading characteristics. In many species,
      countershading was close to the model's prediction of "optimal" countershading
      for SSC. Stronger countershading was associated with increased use of open
      lighting environments, living closer to the equator, and small body size. Abrupt
      transitions from dark to light tones were more common in open lighting
      environments but unassociated with group size or antipredator behavior. Though
      the SSC hypothesis prediction for stronger countershading in diurnal species was
      not supported and noncountershaded or reverse-countershaded species were
      unexpectedly common, this basic pattern of associations is explained only by the
      SSC hypothesis. Despite extreme variation in lighting conditions, many
      terrestrial animals still find protection from predation by compensating for
      their own shadows.

PMID- 23149402
TI  - Positive relationships between association strength and phenotypic similarity
      characterize the assembly of mixed-species bird flocks worldwide.
AB  - Competition theory predicts that local communities should consist of species that
      are more dissimilar than expected by chance. We find a strikingly different
      pattern in a multicontinent data set (55 presence-absence matrices from 24
      locations) on the composition of mixed-species bird flocks, which are important
      subunits of local bird communities the world over. By using null models and
      randomization tests followed by meta-analysis, we find the association strengths
      of species in flocks to be strongly related to similarity in body size and
      foraging behavior and higher for congeneric compared with noncongeneric species
      pairs. Given the local spatial scales of our individual analyses, differences in
      the habitat preferences of species are unlikely to have caused these association
      patterns; the patterns observed are most likely the outcome of species
      interactions. Extending group-living and social-information-use theory to a
      heterospecific context, we discuss potential behavioral mechanisms that lead to
      positive interactions among similar species in flocks, as well as ways in which
      competition costs are reduced. Our findings highlight the need to consider
      positive interactions along with competition when seeking to explain community
      assembly.

PMID- 23149403
TI  - Community-level consequences of cannibalism.
AB  - Ecological interactions determine the structure and dynamics of communities and
      their responses to the environment. Understanding the community-level effects of
      ecological interactions, such as intra- and interspecifc competition, predation,
      and cannibalism, is therefore central to ecological theory and ecosystem
      management. Here, we investigate the community-level consequences of cannibalism
      in populations with density-dependent maturation and reproduction. We model a
      stage-structured consumer population with an ontogenetic diet shift to analyze
      how cannibalism alters the conditions for the invasion and persistence of stage
      specific predators and competitors. Our results demonstrate that cannibalistic
      interactions can facilitate coexistence with other species at both trophic
      levels. This effect of cannibalism critically depends on the food dependence of
      the demographic processes. The underlying mechanism is a cannibalism-induced
      shift in the biomass distribution between the consumer life stages. These
      findings suggest that cannibalism may alter the structure of ecological
      communities through its effects on species coexistence.

PMID- 23149405
TI  - Rapid change in the thermal tolerance of a tropical lizard.
AB  - The predominant view is that the thermal physiology of tropical ectotherms,
      including lizards, is not labile over ecological timescales. We used the recent
      introduction (~35 years ago) of the Puerto Rican lizard Anolis cristatellus to
      Miami, Florida, to test this thermal rigidity hypothesis. We measured lower
      (critical thermal minimum [CT(min)]) and upper (critical thermal maximum
      [CT(max)]) thermal tolerances and found that the introduced population tolerates
      significantly colder temperatures (by ~3 degrees C) than does the Puerto Rican
      source population; however, CT(max) did not differ. These results mirror the
      thermal regimes experienced by each population: Miami reaches colder ambient
      temperatures than Puerto Rico, but maximum ambient temperatures are similar. The
      differences in CT(min) were observed even though lizards from both sites
      experienced nearly identical conditions for 49 days before CT(min) measurement.
      Our results demonstrate that changes in thermal tolerance occurred relatively
      rapidly (~35 generations), which strongly suggests that the thermal physiology of
      tropical lizards is more labile than previously proposed.

PMID- 23149404
TI  - Male pregnancy and biparental immune priming.
AB  - In vertebrates, maternal transfer of immunity via the eggs or placenta provides
      offspring with crucial information on prevailing pathogens and parasites. Males
      contribute little to such transgenerational immune priming, either because they
      do not share the environment and parasite pressure of the offspring or because
      sperm are too small for transfer of immunity. In the teleost group of Syngnathids
      (pipefish, seahorses, and sea dragons), males brood female eggs in a placenta
      like structure. Such sex-role-reversed species provide a unique opportunity to
      test for adaptive plasticity in immune transfer. Here, males and females should
      both influence offspring immunity. We experimentally tested paternal effects on
      offspring immunity by examining immune cell proliferation and immune gene
      expression. Maternal and paternal bacterial exposure induced offspring immune
      defense 5 weeks after hatching, and this effect persisted in 4-month-old
      offspring. For several offspring immune traits, double parental exposure
      (maternal and paternal) enhanced the response, whereas for another group of
      immune traits, the transgenerational induction already took place if only one
      parent was exposed. Our study shows that sex role reversal in connection with
      male pregnancy opens the door for biparental influences on offspring immunity and
      may represent an additional advantage for the evolution of male pregnancy.

PMID- 23149406
TI  - Intraseasonal variation in reproductive effort: young males finish last.
AB  - Age-dependent reproductive timing has been observed in females of a number of
      species; older females often breed earlier in the season and experience higher
      reproductive success as a result. However, to date, evidence for within-season
      variation in reproductive effort (RE) for males has been relatively weak. Males
      are expected to time RE in light of intraseasonal variations in the availability
      of receptive females and competition with other males. Young males, which are
      typically smaller and less experienced, might benefit from breeding later in the
      season, when male-male competition is less intense. Using a long-term data set of
      Alpine chamois Rupicapra rupicapra, we sought to evaluate the hypothesis that
      younger males allocate highest RE late in the breeding season, at a time when
      older male RE has decreased substantially. Our results support this hypothesis,
      which suggests that intraseasonal variation in RE may be an adaptive life-history
      trait for males as well as females.

PMID- 23149409
TI  - Neutral dynamics and cluster statistics in a tropical forest.
AB  - The neutral theory of biodiversity attributes community structure to the effects
      of chance alone, assuming that all species and individuals are demographically
      equivalent. Here we present a spatially explicit version of the neutral theory
      and test it against the Barro Colorado Island (BCI) data. Monitoring the dynamics
      of clusters, we show that the effect of local heterogeneities (e.g.,
      microtopography) is weak, making a spatially homogenous model plausible. We then
      compare the cluster statistics of the three most frequent species with the
      patterns obtained from neutral dynamics, examining two families of recruitment
      kernels: one that interpolates between a limited distance and panmictic dispersal
      (local-global) and one that assumes a scale-free Cauchy kernel. The results rule
      out the local-global dispersal model and show that the spatial patterns fit very
      nicely those obtained from the fat-tailed kernel. Our work emphasizes the
      importance of spatiotemporal cluster dynamics as an instrument for detecting the
      factors that govern community assembly.

PMID- 23149410
TI  - The balanced lethal system of crested newts: a ghost of sex chromosomes past?
AB  - Balanced lethal systems are more than biological curiosities: as theory predicts,
      they should quickly be eliminated through the joint forces of recombination and
      selection. That such systems might become fixed in natural populations poses a
      challenge to evolutionary theory. Here we address the case of a balanced lethal
      system fixed in crested newts and related species, which makes 50% of offspring
      die early in development. All adults are heteromorphic for chromosome pair 1. The
      two homologues (1A and 1B) have different recessive deleterious alleles fixed on
      a nonrecombining segment, so that heterozygotes are viable, while homozygotes are
      lethal. Given such a strong segregation load, how could autosomes stop
      recombining? We propose a role for a sex-chromosome turnover from pair 1
      (putative ancestral sex chromosome) to pair 4 (currently active sex chromosome).
      Accordingly, 1A and 1B represent two variants (Y(A) and Y(B)) of the Y chromosome
      from an ancestral male-heterogametic system. We formalize a scenario in which
      turnovers are driven by sex ratio selection stemming from gene-environment
      interactions on sex determination. Individual-based simulations show that a
      balanced lethal system can be fixed with significant likelihood, provided the
      masculinizing allele on chromosome 4 appears after the elimination of the
      feminizing allele on chromosome 1. Our study illustrates how strikingly
      maladaptive traits might evolve through natural selection.

PMID- 23149412
TI  - Retinol might stabilize sperm acrosomal membrane in situations of oxidative
      stress because of high temperatures.
AB  - High temperatures have negative effects on sperm quality leading to temporary or
      permanent sterility. The study tried to confirm the harmful effects of high
      temperatures on epididymal sperm cells in comparison with other temperatures
      (scrotal, environmental, and refrigeration temperatures), the main objective was
      the assessment of the addition of retinol as an antioxidant agent to improve
      sperm quality parameters. Testes from 10 bulls were collected from a
      slaughterhouse. Sperm cells were flushed from the cauda epididymis and deferent
      duct and assessed for sperm quality parameters at recovery. Afterward, sperm cell
      samples were exposed to one of four different temperatures (4  degrees C, 22 
      degrees C, 32  degrees C, and 41.5  degrees C for 3 hours) in presence or absence
      of retinol in the storage extender. Percentages of viability and morphologic
      abnormalities were determined using eosin-nigrosin staining. Acrosome integrity
      and sperm plasma membrane integrity were assessed by fluorescence Pisum sativum
      agglutinin lectin (FITC-PSA) staining and the hypo-osmotic swelling test,
      respectively. Total and progressive motility were analyzed by computer-assisted
      sperm analysis. Sperm quality parameters were mainly affected by high
      temperatures (41.5  degrees C). The addition of all-trans-retinol to the storage
      extender did not show any effect on sperm quality parameters. However, the
      percentage of sperm cells with altered acrosome was significantly reduced when
      retinol was present in the extender under heat stress conditions (41.5  degrees
      C). In conclusion, retinol might stabilize sperm acrosomal membrane in situations
      of oxidative stress because of high temperatures.

PMID- 23149413
TI  - Data-derived reference profiles with corepresentation of progesterone, estradiol,
      LH, and FSH dynamics during the bovine estrous cycle.
AB  - Subfertility in cows is often associated with alterations in the hormonal
      patterns involved in the regulation of the estrous cycle. Reference profiles are
      needed to ground modeling projects aimed at describing these alterations and to
      develop tools for detecting abnormal dynamics. Various schematic views of LH,
      FSH, progesterone (P4) and estradiol (E2) patterns have been published but with
      no clear indication of the extent to which they are derived from real data. The
      objective of this study was to generate standard profiles for the main
      reproductive hormones that can be proposed as reliable references to represent
      the normal dynamics of these hormones over the estrous cycle. A database of
      hormonal profiles was compiled with 40, 23, 33, and 34 profiles for LH, FSH, E2,
      and P4, respectively, derived from publications in which changes over time of at
      least three of these four hormones, including LH, were reported. These profiles
      were digitalized and standardized over the time throughout the estrous cycle,
      considering the interval between two successive LH surges to be 21 days. After
      this standardization on the x-axis, a transformation on the y-axis was performed
      to center the profiles around their common dynamics. For each hormone, the
      reference profile was then considered to be the median of the adjusted profiles.
      Quartiles were reported to account for the time evolution of the variability
      around each reference profile. The reference profiles obtained showed that the
      procedure used was satisfactory for extracting the overall changes over time of
      LH, P4, and E2. Results were less satisfactory for FSH, because of a higher
      variability observed between the original profiles in our database. The
      corepresentation of the reference profiles, i.e., when depicted together on the
      same scale, emphasizes the interplay between these hormones more precisely than
      most of the schematic views available in literature. These data-derived profiles
      can be considered to be generic and useful for benchmarking the normal dynamics
      of gonadotrophins and steroid hormones over the estrous cycle in cow.

PMID- 23149415
TI  - Enhanced Angpt1/Tie2 signaling affects the differentiation and long-term
      repopulation ability of hematopoietic stem cells.
AB  - Angiopoietin-1 (Angpt1) signaling via the Tie2 receptor regulates vascular and
      hematopoietic systems. To investigate the role of Angpt1-Tie2 signaling in
      hematopoiesis, we prepared conditionally inducible transgenic (Tg) mice
      expressing a genetically engineered Angpt1, cartridge oligomeric matrix protein
      (COMP)-Angpt1. The effects of COMP-Angpt1 overexpression in osteoblasts on
      hematopoiesis were then investigated by crossing COMP-Angpt1 Tg mice with Col1a1
      Cre Tg mice. Interestingly, peripheral blood analyses showed that 4 week (wk)-old
      (but not 8 wk-old) Col1a1-Cre+/COMP-Angpt1+ mice had a lower percentage of
      circulating B cells and a higher percentage of myeloid cells than Col1a1-Cre
      /COMP-Angpt1+ (control) mice. Although there were no significant differences in
      the immunophenotypic hematopoietic stem and progenitor cell (HSPC) populations
      between Col1a1-Cre+/COMP-Angpt1+ and control mice, lineage(-)Sca-1(+)c-Kit(+)
      (LSK) cells isolated from 8 wk-old Col1a1-Cre+/COMP-Angpt1+ mice showed better
      long-term bone marrow reconstitution ability. These data indicate that Angpt1
      Tie2 signaling affects the differentiation capacity of hematopoietic lineages
      during development and increases the stem cell activity of HSCs.

PMID- 23149414
TI  - Vitamin D directly regulates Mdm2 gene expression in osteoblasts.
AB  - While Mdm2 is an important negative regulator of the p53 tumor suppressor, it
      also possesses p53-independent functions in cellular differentiation processes.
      Mdm2 expression is alternatively regulated by two P1 and P2 promoters. In this
      study we show that the P2-intiated transcription of Mdm2 gene is activated by
      1,25-dihydroxy vitamin D3 in MC3T3 cells. By using P1 and P2-specific reporters,
      we demonstrate that only the P2-promoter responds to vitamin D treatment. We have
      further identified a potential vitamin D receptor responsive element proximal to
      the two p53 response elements within the Mdm2 P2 promoter. Using cell lines that
      are p53-temperature sensitive and p53-null, we show requirement of p53 for VDR
      mediated up regulation of Mdm2 expression. Our results indicate that 1,25
      dihydroxy vitamin D3 and its receptor have a role in the regulation of P2
      initiated Mdm2 gene expression in a p53-dependent way.

PMID- 23149416
TI  - Angiotensin-receptor blockers and risk of Alzheimer's disease in hypertension
      population--a nationwide cohort study.
AB  - BACKGROUND: Although emerging evidence shows angiotensin-receptor blockers (ARBs)
      may have a beneficial effect against Alzheimer's disease (AD), the association is
      not consistent. We investigated the association between ARB use and the risk of
      development of AD using a nationwide, population-based cohort database in Taiwan.
      METHODS AND RESULTS: In total, 16,426 newly diagnosed hypertensive patients who
      were administered ARB without a previous diagnosis of AD were identified from the
      Taiwan National Health Insurance database. The comparison group consisted of
      hypertensive patients who did not receive ARB, and were matched to exposed
      individuals using propensity score by enrolled time, age, sex, and comorbidities.
      During an average of 5.24 +/- 2.01 years of follow-up, a total of 1,031 cases
      (3.13%) of new AD occurred. The log-rank test showed no significant difference in
      the AD occurrence rate between subjects exposed to ARBs and non-exposed controls
      [488 (2.97%) vs. 543 (3.29%), P=0.221]. After adjusting for age, sex,
      comorbidities, and medications, only advanced age [hazard ratio (HR) 1.12, 95%
      confidence interval (CI) 1.12-1.13, P<0.001), female sex (HR 1.18, 95% CI 1.04
      1.33, P=0.011), diabetes (HR 1.53, 95% CI 1.31-1.79, P<0.001), but not ARB (HR
      1.08, 95% CI 0.96-1.22, P=0.222) were independently associated with AD
      development. CONCLUSIONS: The use of ARB was not significantly associated with a
      reduction of risk of AD in Asian patients with essential hypertension.

PMID- 23149417
TI  - Impact of carotid artery ultrasound and ankle-brachial index on prediction of
      severity of SYNTAX score.
AB  - BACKGROUND: Numerous reports have shown that both carotid artery ultrasound
      (carotid US) findings and ankle-brachial index (ABI) are associated with the
      prevalence of coronary artery disease. The relationship between carotid US
      findings and ABI and the complexity of coronary artery disease (as measured by
      SYNTAX [SX] score), was evaluated. METHODS AND RESULTS: The subjects included 496
      consecutive patients who underwent carotid US, ABI analysis and initial coronary
      angiography. The mean common carotid artery intima-media thickness (mean IMT) was
      evaluated on carotid US. Patients with mean IMT >= 0.9 mm had significantly
      higher SX scores than patients without thickening (mean IMT <0.9 mm; P<0.0001).
      Similarly, patients with low ABI (<0.9) had significantly higher SX scores than
      patients with ABI >= 0.9 (P<0.0001). When the patients were divided into 4 groups
      on the basis of mean IMT and ABI (group A, mean IMT <0.9 mm, ABI >= 0.9; group B,
      mean IMT <0.9 mm, low ABI; group C, mean IMT >= 0.9 mm, ABI >= 0.9; group D, mean
      IMT >= 0.9 mm, low ABI), the SX scores were significantly different. Among the
      patients in group D, 75% had coronary artery disease. CONCLUSIONS: Carotid US and
      ABI are associated with SX score. The combination of carotid US and ABI provides
      useful information for predicting the complexity and presence of coronary artery
      disease.

PMID- 23149418
TI  - Validity and reliability of new intravascular ultrasound analysis software for
      morphological measurement of coronary artery disease.
AB  - BACKGROUND: Intravascular ultrasound (IVUS) analysis software enables precise
      planimetry measurement and tissue characterization of coronary plaque. Recently,
      a new IVUS analysis software compatible with integrated backscatter-IVUS,
      VISIATLAS(TM), was developed. The validity and reliability of VISIATLAS(TM) were
      evaluated. METHODS AND RESULTS: Forty patients who underwent IVUS-guided
      percutaneous coronary intervention were enrolled, and planimetry measurements
      were performed by 2 observers using VISIATLAS(TM) and echoPlaque(TM). IVUS
      analysis was performed in non-stent segments in 10 patients (non-target vessel,
      n=5; target vessel before stent implantation, n=5) at every 2.5mm for 20 slices
      in each patient. Stent segments were analyzed in the remaining 30 patients. With
      VISIATLAS(TM), the intraobserver and interobserver intraclass correlation
      coefficients (ICC) for the area of external elastic membrane (EEM), lumen, and
      plaque plus media (P+M) were 0.999 and 0.999, 0.996 and 0.993, and 0.993 and
      0.991, respectively. The intersoftware ICC for EEM, lumen, and P+M area were
      0.997, 0.993, and 0.985, respectively. The ICC of stent volume for intraobserver,
      interobserver and intersoftware comparisons were 0.997, 0.993, and 0.998,
      respectively. Bland-Altman plots showed small differences and narrow limits of
      agreement for all of the above parameters. CONCLUSIONS: VISIATLAS(TM) has high
      repeatability and reproducibility of measurement. This new IVUS analysis software
      is suitable for accurate measurement of coronary artery and stent structure in
      future IVUS studies.

PMID- 23149419
TI  - Influence of endophyte genotype on swainsonine concentrations in Oxytropis
      sericea.
AB  - Locoism is a toxic syndrome of livestock caused by the ingestion of a subset of
      legumes belonging to the Astragalus and Oxytropis genera known as "locoweeds".
      Locoweeds contain the toxic indolizidine alkaloid swainsonine, which is produced
      by the endophytic fungi Undifilum species. Previously we reported that
      swainsonine concentrations differ between populations of Oxytropis sericea. We
      hypothesized that the genotype of the plant, endophyte, or an interaction of the
      two may be responsible for the differences in swainsonine concentration between
      populations of O. sericea. To test this hypothesis, plants derived from seeds
      collected at each location were grown in a common garden, Undifilum oxytropis
      isolates from each location were cultured and grown in a common environment, and
      a plant genotype by endophyte cross inoculation was performed. Here we show that
      the genotype of the endophyte is responsible for the differences in swainsonine
      concentrations observed in the two populations of O. sericea.

PMID- 23149421
TI  - Highly cis-selective synthesis of iodo-aziridines using diiodomethyllithium and
      in situ generated N-Boc-imines.
AB  - The first preparation of iodoaziridines is described. The addition of
      diiodomethyllithium to N-Boc-imines affords these novel aziridines in high
      yields. The reaction proceeds in one-pot via a highly diastereoselective
      cyclisation of an amino gem-diiodide intermediate.

PMID- 23149422
TI  - Enhanced current-rectification in bilayer graphene with an electrically tuned
      sloped bandgap.
AB  - We propose a novel sloped dielectric geometry in graphene as a band engineering
      method for widening the depletion region and increasing the electrical
      rectification effect in graphene pn junctions. Enhanced current-rectification was
      achieved in a bilayer graphene with a sloped dielectric top gate and a normal
      back gate. A bias was applied to the top gate to induce a spatially modulated and
      sloped band configuration, while a back-gate bias was applied to open a bandgap.
      The sloped band can be tuned to separate n- and p-type regions in the bilayer
      graphene, depending on a suitable choice of gate voltage. The effective depletion
      region between the n- and p-type regions can be spatially enlarged due to the
      proposed top-gate structure. As a result, a strong non-linear electric current
      was observed during drain bias sweeping, demonstrating the expected rectification
      behavior with an on/off ratio higher than all previously reported values for
      graphene pn junctions. The observed rectification was modified to a linear
      current-voltage relationship by adjusting the biases of both gates to form an nn-
      or pp-type junction configuration. These results demonstrate that an external
      voltage can control the current flow in atomic film diodes.

PMID- 23149420
TI  - Creating objects and object categories for studying perception and perceptual
      learning.
AB  - In order to quantitatively study object perception, be it perception by
      biological systems or by machines, one needs to create objects and object
      categories with precisely definable, preferably naturalistic, properties.
      Furthermore, for studies on perceptual learning, it is useful to create novel
      objects and object categories (or object classes) with such properties. Many
      innovative and useful methods currently exist for creating novel objects and
      object categories (also see refs. 7,8). However, generally speaking, the existing
      methods have three broad types of shortcomings. First, shape variations are
      generally imposed by the experimenter, and may therefore be different from the
      variability in natural categories, and optimized for a particular recognition
      algorithm. It would be desirable to have the variations arise independently of
      the externally imposed constraints. Second, the existing methods have difficulty
      capturing the shape complexity of natural objects. If the goal is to study
      natural object perception, it is desirable for objects and object categories to
      be naturalistic, so as to avoid possible confounds and special cases. Third, it
      is generally hard to quantitatively measure the available information in the
      stimuli created by conventional methods. It would be desirable to create objects
      and object categories where the available information can be precisely measured
      and, where necessary, systematically manipulated (or 'tuned'). This allows one to
      formulate the underlying object recognition tasks in quantitative terms. Here we
      describe a set of algorithms, or methods, that meet all three of the above
      criteria. Virtual morphogenesis (VM) creates novel, naturalistic virtual 3-D
      objects called 'digital embryos' by simulating the biological process of
      embryogenesis. Virtual phylogenesis (VP) creates novel, naturalistic object
      categories by simulating the evolutionary process of natural selection. Objects
      and object categories created by these simulations can be further manipulated by
      various morphing methods to generate systematic variations of shape
      characteristics. The VP and morphing methods can also be applied, in principle,
      to novel virtual objects other than digital embryos, or to virtual versions of
      real-world objects. Virtual objects created in this fashion can be rendered as
      visual images using a conventional graphical toolkit, with desired manipulations
      of surface texture, illumination, size, viewpoint and background. The virtual
      objects can also be 'printed' as haptic objects using a conventional 3-D
      prototyper. We also describe some implementations of these computational
      algorithms to help illustrate the potential utility of the algorithms. It is
      important to distinguish the algorithms from their implementations. The
      implementations are demonstrations offered solely as a 'proof of principle' of
      the underlying algorithms. It is important to note that, in general, an
      implementation of a computational algorithm often has limitations that the
      algorithm itself does not have. Together, these methods represent a set of
      powerful and flexible tools for studying object recognition and perceptual
      learning by biological and computational systems alike. With appropriate
      extensions, these methods may also prove useful in the study of morphogenesis and
      phylogenesis.

PMID- 23149423
TI  - Percutaneous lumbar pedicle screw placement aided by computer-assisted
      fluoroscopy-based navigation: perioperative results of a prospective,
      comparative, multicenter study.
AB  - STUDY DESIGN: Institutional review board-approved, prospective, multicenter,
      comparative study. OBJECTIVE: To assess the accuracy and utility of a computer
      assisted fluoroscopic navigation method for percutaneous placement of lumbar
      pedicle screws compared with conventional fluoroscopic placement. SUMMARY OF
      BACKGROUND DATA: Recent reports indicate that cortical breaches during
      percutaneous pedicle screw placement can exceed 15%. Computed tomography (CT)-
      and fluoroscopy-based navigation systems may facilitate increased placement
      accuracy with reduced radiation exposure and operative times. METHODS: Patients
      were alternately assigned to either the Guidance or Control group. The Guidance
      group underwent lumbar pedicle screw placement using the oblique visualization
      technique and computer-assisted fluoroscopic navigation. The Control group
      underwent lumbar pedicle screw placement per standard percutaneous technique
      aided by fluoroscopy alone. Baseline demographics, visual analog scale (VAS) pain
      scores, and American Spinal Injury Association scores were obtained
      preoperatively and in the immediate postoperative period. Fluoroscopy times and
      guidewire insertion times were recorded intraoperatively. All postoperative CT
      scans were reviewed by an independent spine surgeon to grade screw placement
      accuracy. RESULTS: Forty-two patients (210 screws) were assigned to the Guidance
      group and 34 patients (152 screws) were assigned to the Control group. Use of
      Guidance resulted in reduced average fluoroscopy usage per pedicle [6.6 sec (SD =
      5.1) vs. 9.6 sec (SD 6.2), P < 0.001] and more expedient placement of guidewires
      per pedicle [3.65 min (SD = 2.31) vs. 4.43 min (SD = 2.56), P = 0.003]. The
      Guidance group experienced less than half of the breach rate of the Control group
      (3.0% vs. 7.2%, P = 0.055) and reduced breach magnitudes. None of the breaches
      resulted in a corresponding neurological deficit or required revision. All
      patient-reported outcomes were significantly improved after surgery and there
      were no significant differences in average postoperative VAS scores between
      treatment groups. CONCLUSION: Use of Guidance reduces fluoroscopy and insertion
      times with increased accuracy compared with conventional fluoroscopic methods of
      percutaneous pedicle screw insertion.

PMID- 23149425
TI  - TULA-2, a novel histidine phosphatase, regulates bone remodeling by modulating
      osteoclast function.
AB  - Bone is a dynamic tissue that depends on the intricate relationship between
      protein tyrosine kinases (PTK) and protein tyrosine phosphatases (PTP) for
      maintaining homeostasis. PTKs and PTPs act like molecular on and off switches and
      help modulate differentiation and the attachment of osteoclasts to bone matrix
      regulating bone resorption. The protein T cell ubiquitin ligand-2 (TULA-2), which
      is abundantly expressed in osteoclasts, is a novel histidine phosphatase. Our
      results show that of the two family members, only TULA-2 is expressed in
      osteoclasts and that its expression is sustained throughout the course of
      osteoclast differentiation, suggesting that TULA-2 may play a role during early
      as well late stages of osteoclast differentiation. Skeletal analysis of mice that
      do not express TULA or TULA-2 proteins (DKO mice) revealed that there was a
      decrease in bone volume due to increased osteoclast numbers and function.
      Furthermore, in vitro experiments indicated that bone marrow precursor cells from
      DKO mice have an increased potential to form osteoclasts. At the molecular level,
      the absence of TULA-2 in osteoclasts results in increased Syk phosphorylation at
      the Y352 and Y525/526 residues and activation of phospholipase C gamma 2
      (PLCgamma2) upon engagement of immune-receptor-tyrosine-based-activation-motif
      (ITAM)-mediated signaling. Furthermore, expression of a phosphatase-dead TULA-2
      leads to increased osteoclast function. Taken together, these results suggest
      that TULA-2 negatively regulates osteoclast differentiation and function.

PMID- 23149426
TI  - Stress reduction in the secondary prevention of cardiovascular disease:
      randomized, controlled trial of transcendental meditation and health education in
      Blacks.
AB  - BACKGROUND: Blacks have disproportionately high rates of cardiovascular disease.
      Psychosocial stress may contribute to this disparity. Previous trials on stress
      reduction with the Transcendental Meditation (TM) program have reported
      improvements in cardiovascular disease risk factors, surrogate end points, and
      mortality in blacks and other populations. METHODS AND RESULTS: This was a
      randomized, controlled trial of 201 black men and women with coronary heart
      disease who were randomized to the TM program or health education. The primary
      end point was the composite of all-cause mortality, myocardial infarction, or
      stroke. Secondary end points included the composite of cardiovascular mortality,
      revascularizations, and cardiovascular hospitalizations; blood pressure;
      psychosocial stress factors; and lifestyle behaviors. During an average follow-up
      of 5.4 years, there was a 48% risk reduction in the primary end point in the TM
      group (hazard ratio, 0.52; 95% confidence interval, 0.29-0.92; P=0.025). The TM
      group also showed a 24% risk reduction in the secondary end point (hazard ratio,
      0.76; 95% confidence interval, 0.51-0.1.13; P=0.17). There were reductions of 4.9
      mmHg in systolic blood pressure (95% confidence interval -8.3 to -1.5 mmHg;
      P=0.01) and anger expression (P<0.05 for all scales). Adherence was associated
      with survival. CONCLUSIONS: A selected mind-body intervention, the TM program,
      significantly reduced risk for mortality, myocardial infarction, and stroke in
      coronary heart disease patients. These changes were associated with lower blood
      pressure and psychosocial stress factors. Therefore, this practice may be
      clinically useful in the secondary prevention of cardiovascular disease. Clinical
      Trial Registration- URL: www.clinicaltrials.gov Unique identifier: NCT01299935.

PMID- 23149427
TI  - Why does primary angioplasty not work in registries? Quantifying the
      susceptibility of real-world comparative effectiveness data to allocation bias.
AB  - BACKGROUND: Meta-analysis of registries (comparative effectiveness research)
      shows that primary angioplasty and fibrinolysis have equivalent real-world
      survival. Yet, randomized, controlled trials consistently find primary
      angioplasty superior. Can unequal allocation of higher-risk patients in
      registries have masked primary angioplasty benefit? METHODS AND RESULTS: First,
      we constructed a model to demonstrate the potential effect of allocation bias. We
      then analyzed published registries (55022 patients) for allocation of higher-risk
      patients (Killip class >=1) to determine whether the choice of reperfusion
      therapy was affected by the risk level of the patient. Meta-regression was used
      to examine the relationship between differences in allocation of high-risk
      patient to primary angioplasty or fibrinolysis and mortality. Initial modeling
      suggested that registry outcomes are sensitive to allocation bias of high-risk
      patients. Across the registries, the therapy receiving excess high-risk patients
      had worse mortality. Unequal distribution of high-risk status accounted for most
      of the between-registry variance (adjusted R(2)(meta)=83.1%). Accounting for
      differential allocation of higher-risk patients, primary angioplasty gave 22%
      lower mortality (odds ratio, 0.78; 95% confidence interval, 0.64-0.97; P=0.029).
      We derive a formula, called the number needed to abolish, highlighting situations
      in which comparative effectiveness studies are particularly vulnerable to this
      bias. CONCLUSIONS: In ST-segment elevation myocardial infarction, clinicians'
      preference for management of a few high-risk patients can shift mortality
      substantially. Comparative effectiveness research in any disease is vulnerable to
      this, especially diseases with an immediately identifiable high-risk subgroup
      that clinicians prefer to allocate to 1 therapy. For this reason, preliminary
      indications from registry-based comparative effectiveness research should be
      definitively tested by randomized, controlled trials.

PMID- 23149429
TI  - Changes in church-based social support relationships during older adulthood.
AB  - OBJECTIVES: To track the course of age-related changes in emotional and tangible
      support given and received by older adults in the context of their religious
      congregations. METHOD: Hierarchical linear modeling was applied to data from a
      national sample of 1,192 White and African American older adults who attended
      church regularly, and they were interviewed up to four times over a period of
      seven years. RESULTS: Changes were found in six measures of support. Participants
      increased in terms of the amount of emotional support that they both gave and
      received, whereas decreased in the amount of tangible support they gave and
      received. Satisfaction increased with age for both emotional and tangible
      support. There were large race-related differences, with African Americans being
      more engaged in support relationships of all types. Religious factors, including
      frequency of attendance, commitment, and the congregational cohesiveness were
      strong predictors of between-person differences. DISCUSSION: This study is the
      first to demonstrate within-person change in church-based support relationships
      during the course of older adulthood. Patterns of increasing quantity and quality
      of emotional ties, but decreasing tangible support, partially contrast with
      previous findings regarding secular support networks but are consistent with the
      socioemotional selectivity perspective.

PMID- 23149428
TI  - Circulating 25-hydroxy-vitamin D and risk of cardiovascular disease: a meta
      analysis of prospective studies.
AB  - BACKGROUND: Vitamin D status has been linked to the risk of cardiovascular
      disease (CVD). However, the optimal 25-hydroxy-vitamin D (25[OH]-vitamin D)
      levels for potential cardiovascular health benefits remain unclear. METHODS AND
      RESULTS: We searched MEDLINE and EMBASE from 1966 through February 2012 for
      prospective studies that assessed the association of 25(OH)-vitamin D
      concentrations with CVD risk. A total of 24 articles met our inclusion criteria,
      from which 19 independent studies with 6123 CVD cases in 65 994 participants were
      included for a meta-analysis. In a comparison of the lowest with the highest
      25(OH)-vitamin D categories, the pooled relative risk was 1.52 (95% confidence
      interval, 1.30-1.77) for total CVD, 1.42 (95% confidence interval, 1.19-1.71) for
      CVD mortality, 1.38 (95% confidence interval, 1.21-1.57) for coronary heart
      disease, and 1.64 (95% confidence interval, 1.27-2.10) for stroke. These
      associations remained strong and significant when analyses were limited to
      studies that excluded participants with baseline CVD and were better controlled
      for season and confounding. We used a fractional polynomial spline regression
      analysis to assess the linearity of dose-response association between continuous
      25(OH)-vitamin D and CVD risk. The CVD risk increased monotonically across
      decreasing 25(OH)-vitamin D below ~60 nmol/L, with a relative risk of 1.03 (95%
      confidence interval, 1.00-1.06) per 25-nmol/L decrement in 25(OH)-vitamin D.
      CONCLUSIONS: This meta-analysis demonstrated a generally linear, inverse
      association between circulating 25(OH)-vitamin D ranging from 20 to 60 nmol/L and
      risk of CVD. Further research is needed to clarify the association of 25(OH)
      vitamin D higher than 60 nmol/L with CVD risk and assess causality of the
      observed associations.

PMID- 23149430
TI  - Persistent problems in end-of-life planning among young- and middle-aged American
      couples.
AB  - OBJECTIVES: Guided by the transtheoretical model of health behavior change, this
      study sought to explain why (a) rates of advance care planning remain low in the
      general population and (b) surrogate decision makers are often inaccurate about
      patients' end-of-life preferences. METHODS: The study used quantitative data from
      a cross-sectional internet survey conducted between July and October 2010. The
      2,150 participants aged 18-64 belonged to 1,075 married or cohabiting
      heterosexual couples. Participants included members of a nationally
      representative internet panel and a convenience sample from online
      advertisements. RESULTS: Older age was associated with a greater likelihood of
      having executed a living will and/or appointed a durable power of attorney for
      health care. Both older age and poorer health were independently associated with
      a greater likelihood of having discussed end-of-life health care treatment
      preferences. Completion of one's own end-of-life planning was unrelated to one's
      ability to accurately report one's partner's treatment preferences. DISCUSSION:
      Readiness to plan for end of life appears to differ across planning behaviors.
      Age and health are related to aspects of one's own advance care planning, but
      none of these factors are related to accuracy as a partner's surrogate.

PMID- 23149431
TI  - Causal effects of retirement timing on subjective physical and emotional health.
AB  - OBJECTIVES: This article explores the effects of the timing of retirement on
      subjective physical and emotional health. Using panel data from the Health and
      Retirement Study (HRS), we test 4 theory-based hypotheses about these effects
      that retirements maximize health when they happen earlier, later, anytime, or on
      time. METHOD: We employ fixed and random effects regression models with
      instrumental variables to estimate the short- and long-term causal effects of
      retirement timing on self-reported health and depressive symptoms. RESULTS: Early
      retirements--those occurring prior to traditional and legal retirement age-
      dampen health. DISCUSSION: Workers who begin their retirement transition before
      cultural and institutional timetables experience the worst health outcomes; this
      finding offers partial support to the psychosocial-materialist approach that
      emphasizes the benefits of retiring later. Continued employment after
      traditionally expected retirement age, however, offers no health benefits. In
      combination, these findings offer some support for the cultural-institutional
      approach but suggest that we need to modify our understanding of how cultural
      institutional forces operate. Retiring too early can be problematic but no
      disadvantages are associated with late retirements. Raising the retirement age,
      therefore, could potentially reduce subjective health of retirees by expanding
      the group of those whose retirements would be considered early.

PMID- 23149432
TI  - European governments should sue Roche and prescribers should boycott its drugs.

PMID- 23149433
TI  - Prevalence of obesity and associated risk factors among adolescents in Ankara,
      Turkey.
AB  - OBJECTIVE: The purpose of this study was to investigate the prevalence of and the
      risk factors associated with obesity among adolescents in Ankara, Turkey.
      METHODS: The study was conducted in 26 schools in Ankara during the time period
      from September 2010 to March 2011. A total of 8848 adolescents aged 11-18 years
      were chosen using a population-based stratified cluster sampling method. Body
      mass index (BMI) of the participants was compared with the BMI references for
      Turkish children and adolescents to estimate the prevalence of overweight and
      obesity. A standardized questionnaire aiming to determine the sociodemographic
      characteristics, computer use, television (TV) watching, physical activity, and
      presence of obesity in the family was applied to the study group. RESULTS: The
      results showed that the overall prevalence of obesity among adolescents was 7.7%
      (8.4 % for females and 7.0% for males). It was observed that BMI increased as
      computer use increased. A greater proportion of the overweight and obese
      adolescents watched TV and use computer for more than 2 hours/day as compared to
      their normal-weight counterparts. The normal-weight subjects were found to show a
      higher participation in regular physical activity. Obesity prevalence among the
      families of obese adolescents was 56.5%. CONCLUSIONS: The prevalence of
      adolescent obesity in Ankara, Turkey is lower as compared to many European
      countries and to the United States. Computer use, watching TV, physical activity
      and family factors are important risk factors for obesity.

PMID- 23149434
TI  - Hypochondroplasia in a child with 1620C>G (Asn540Lys) mutation in FGFR3.
AB  - Hypochondroplasia (HCP) is an autosomal dominant skeletal dysplasia characterized
      by short extremities, short stature and lumbar lordosis, usually exhibiting a
      phenotype similar to but milder than achondroplasia (ACP). Fibroblast growth
      factor receptor 3 gene (FGFR3) mutations in the germline are well-known causes of
      skeletal syndromes. FGFR3 is a negative regulator of bone growth and all
      mutations in FGFR3 are gain-of-function mutations that lead to skeletal
      dysplasias. We report a child who presented with short stature, a relatively long
      trunk, short legs, short arm span, radiographic evidence of HCP and mild mental
      retardation. Genetic analysis revealed a heterozygous 1620C>G (Asn540Lys)
      mutation in FGFR3. To our knowledge, ours is the first case report of HCP with a
      heterozygous 1620C>G (Asn540Lys) mutation in Turkey.

PMID- 23149435
TI  - Moderate systemic hypothermia decreases burn depth progression.
AB  - BACKGROUND: Therapeutic hypothermia has been proposed to be beneficial in an
      array of human pathologies including cardiac arrest, stroke, traumatic brain and
      spinal cord injury, and hemorrhagic shock. Burn depth progression is
      multifactorial but inflammation plays a large role. Because hypothermia is known
      to reduce inflammation, we hypothesized that moderate hypothermia will decrease
      burn depth progression. METHODS: We used a second-degree 15% total body surface
      area thermal injury model in rats. Burn depth was assessed by histology of biopsy
      sections. Moderate hypothermia in the range of 31-33 degrees C was applied for 4h
      immediately after burn and in a delayed fashion, starting 2h after burn. In order
      to gain insight into the beneficial effects of hypothermia, we analyzed global
      gene expression in the burned skin. RESULTS: Immediate hypothermia decreased burn
      depth progression at 6h post injury, and this protective effect was sustained for
      at least 24h. Burn depth was 18% lower in rats subjected to immediate hypothermia
      compared to control rats at both 6 and 24h post injury. Rats in the delayed
      hypothermia group did not show any significant decrease in burn depth at 6h, but
      had 23% lower burn depth than controls at 24h. Increased expression of several
      skin-protective genes such as CCL4, CCL6 and CXCL13 and decreased expression of
      tissue remodeling genes such as matrix metalloprotease-9 were discovered in the
      skin biopsy samples of rats subjected to immediate hypothermia. CONCLUSIONS:
      Systemic hypothermia decreases burn depth progression in a rodent model and up
      regulation of skin-protective genes and down-regulation of detrimental tissue
      remodeling genes by hypothermia may contribute to its beneficial effects.

PMID- 23149437
TI  - Brugada syndrome: two decades of progress.
AB  - Two decades ago, a series of 8 idiopathic ventricular fibrillation patients who
      each had an abnormal ECG (right bundle branch block with coved-type ECG), but
      otherwise had normal hearts were described by Brugada and Brugada. Since then,
      the clinical entity has become known as Brugada syndrome (BS). Shortly
      thereafter, mutations of the SCN5A gene that encodes for the alpha-subunit of the
      sodium channel were found, galvanizing the field of ion channelopathies following
      in the footsteps of the breakthrough in long QT syndrome. Over the past 20 years,
      extensive research in this field has produced major progress toward better
      understanding of BS and the gaining of knowledge of the genetic background,
      pathophysiology and new management. Two consensus reports were published to help
      define the diagnostic criteria, risk stratification and management of BS
      patients. However, there are controversies. In this review, we will share our
      experiences of BS patients in Thailand and discuss advances in many aspects of
      the syndrome (ie, genetics and pathophysiology) and some of these pertinent
      controversies, as well as new treatment of the syndrome with catheter ablation.

PMID- 23149436
TI  - Antigenic determinants of hepatitis E virus and vaccine-induced immunogenicity
      and efficacy.
AB  - There is emerging evidence for an under-recognized hepatitis E virus (HEV) as a
      human pathogen. Among different reasons for this neglect are the unsatisfactory
      performance and under-utilization of commercial HEV diagnostic kits; for
      instance, the number of anti-HEV IgM kits marketed in China is about one-fifth of
      that of hepatitis A kits. Over the last two decades, substantial progress has
      been achieved in furthering our knowledge on the HEV-specific immune responses,
      antigenic features of HEV virions, and development of serological assays and more
      recently prophylactic vaccines. This review will focus on presenting the evidence
      of the importance of HEV infection for certain cohorts such as pregnant women,
      the key antigenic determinants of the virus, and immunogenicity and clinical
      efficacy conferred by a newly developed prophylactic vaccine. Robust
      immunogenicity, greater than 195-fold and approximately 50-fold increase of anti
      HEV IgG level in seronegative and seropositive vaccinees, respectively, as well
      as impressive clinical efficacy of this vaccine was demonstrated. The protection
      rate against the hepatitis E disease and the virus infection was shown to be 100%
      (95% CI 75-100) and 78% (95% CI 66-86), respectively.

PMID- 23149438
TI  - Magnetic anisotropy considerations in magnetic force microscopy studies of single
      superparamagnetic nanoparticles.
AB  - In recent years, superparamagnetic nanoparticles (SPNs) have become increasingly
      important in applications ranging from solid state memory devices to biomedical
      diagnostic and therapeutic tools. However, detection and characterization of the
      small and unstable magnetic moment of an SPN at the single particle level remains
      a challenge. Further, depending on their physical shape, crystalline structure or
      orientation, SPNs may also possess magnetic anisotropy, which can govern the
      extent to which their magnetic moments can align with an externally applied
      magnetic field. Here, we demonstrate how we can exploit the magnetic anisotropy
      of SPNs to enable uniform, highly-sensitive detection of single SPNs using
      magnetic force microscopy (MFM) in ambient air. Superconducting quantum
      interference device magnetometry and analytical transmission electron microscopy
      techniques are utilized to characterize the collective magnetic behavior,
      morphology and composition of the SPNs. Our results show how the consideration of
      magnetic anisotropy can enhance the ability of MFM to detect single SPNs at
      ambient room temperature with high force sensitivity and spatial resolution.

PMID- 23149439
TI  - Ex vivo organotypic corneal model of acute epithelial herpes simplex virus type I
      infection.
AB  - Herpes keratitis is one of the most severe pathologies associated with the herpes
      simplex virus-type 1 (HSV-1). Herpes keratitis is currently the leading cause of
      both cornea-derived and infection-associated blindness in the developed world.
      Typical presentation of herpes keratitis includes infection of the corneal
      epithelium and sometimes the deeper corneal stroma and endothelium, leading to
      such permanent corneal pathologies as scarring, thinning, and opacity. Corneal
      HSV-1 infection is traditionally studied in two types of experimental models. The
      in vitro model, in which cultured monolayers of corneal epithelial cells are
      infected in a Petri dish, offers simplicity, high level of replicability, fast
      experiments, and relatively low costs. On the other hand, the in vivo model, in
      which animals such as rabbits or mice are inoculated directly in the cornea,
      offers a highly sophisticated physiological system, but has higher costs, longer
      experiments, necessary animal care, and a greater degree of variability. In this
      video article, we provide a detailed demonstration of a new ex vivo model of
      corneal epithelial HSV-1 infection, which combines the strengths of both the in
      vitro and the in vivo models. The ex vivo model utilizes intact corneas
      organotypically maintained in culture and infected with HSV-1. The use of the ex
      vivo model allows for highly physiologically-based conclusions, yet it is rather
      inexpensive and requires time commitment comparable to that of the in vitro
      model.

PMID- 23149440
TI  - Therapeutic drug monitoring of common antipsychotics.
AB  - The aim of this review is to provide information for interpreting outcome results
      from monitoring of antipsychotics in biological samples. A brief overview of the
      working mechanisms, pharmacological effects, drug interactions, and analytical
      methods of classical and atypical antipsychotics is given. Nineteen
      antipsychotics were selected based on their importance in the worldwide market as
      follows: amisulpride, aripiprazole, asenapine, bromperidol, clozapine,
      flupenthixol, haloperidol, iloperidone, lurasidone, olanzapine, paliperidone,
      perphenazine, pimozide, pipamperone, quetiapine, risperidone, sertindole,
      sulpiride, and zuclopenthixol. A straightforward relationship between
      administered dose, plasma or serum concentration, clinical outcome, or adverse
      effects is often lacking. Nowadays, focus lies on therapeutic drug monitoring and
      individualized therapy to find adequate treatment, to explain treatment failure
      or nonresponse, and to check patient compliance. However, extensive research in
      this field is still mandatory.

PMID- 23149441
TI  - Impact of tacrolimus intraindividual variability and CYP3A5 genetic polymorphism
      on acute rejection in kidney transplantation.
AB  - BACKGROUND: Wide variation in tacrolimus concentrations and low tacrolimus
      exposure have been reported to be associated with poor renal graft outcomes in
      non-Asians. The CYP3A5 polymorphism is a representative genetic factor that might
      affect this association, together with environmental factors. We investigated
      whether tacrolimus variability or the mean tacrolimus trough concentration can
      influence kidney allograft outcomes in Asians and whether the CYP3A5 polymorphism
      (rs776746) can affect this relationship. METHODS: Data from renal transplant
      patients between 2000 and 2010 were analyzed retrospectively. The tacrolimus
      intraindividual variability (IIV) and the mean tacrolimus trough concentration
      were calculated from the tacrolimus concentrations between 6 and 12 months after
      transplantation. RESULTS: A total of 249 renal transplant patients were enrolled.
      The patients with higher tacrolimus IIV had shorter rejection-free survival (P =
      0.002). However, there was no difference in rejection-free survival between
      CYP3A5 expressers and nonexpressers. The tacrolimus IIV was not associated with
      the CYP3A5 polymorphism. High IIV of tacrolimus was an independent risk factor of
      biopsy-proven acute rejection after adjusting for mean tacrolimus concentration,
      HLA mismatch, induction therapy, donor type, and CYP3A5 polymorphism (hazard
      ratio 2.655, 95% confidence interval 1.394-5.056). Interestingly, the impact of
      tacrolimus IIV on acute rejection was significant in CYP3A5 expressers, whereas
      it was not in CYP3A5 nonexpressers. CONCLUSIONS: The IIV of tacrolimus trough
      concentrations had a significant impact on rejection-free survival. The effect
      was influenced by CYP3A5 polymorphism, although the tacrolimus variability itself
      was not determined by the CYP3A5 polymorphism.

PMID- 23149442
TI  - Should thiopurine methyltransferase genotypes and phenotypes be measured before
      thiopurine therapy in patients with inflammatory bowel disease?
AB  - BACKGROUND AND AIMS: Not all of the adverse effects to thiopurine therapy can be
      explained by thiopurine methyltransferase (TPMT) polymorphisms. This study was
      intended to evaluate the value of TPMT genotype and phenotype measurement during
      the first year of thiopurine therapy. METHODS: Consecutive patients with
      inflammatory bowel disease (IBD) who were receiving azathioprine or 6
      mercaptopurine were followed up for 12 months. TPMT genotypes and phenotypes were
      examined in patients with IBD before thiopurine therapy and in unrelated healthy
      volunteers by polymerase chain reaction and high-performance liquid
      chromatography. RESULTS: A total of 199 patients and 300 healthy volunteers were
      included at 2 centers. Forty-seven of the 199 patients (23.62%) exhibited adverse
      effects during the entire course of thiopurine therapy. Two (1%) patients
      carrying TPMT*3C developed leucopenia at week 4 of azathioprine treatment. The
      TPMT*3C had a specificity of 100% (163/163) but a sensitivity of 5.56% (2/36) for
      predicting leucopenia. The calculated optimal cutoff activity for high TPMT
      activity and decreased TPMT activity was 4.75 U/mL red blood cells. The risk of
      leucopenia increased in the decreased TPMT group (odds ratio: 20.25; 95%
      confidence interval: 2.19-187.17; P = 0.004) and increased more during the
      initial 3 months of thiopurine therapy (odds ratio: 34.80; 95% confidence
      interval: 3.71-326.77; P = 0.001). Leucopenia occurred more frequently in the
      patients cotreated with 5-aminosalicylates than in those not cotreated (32.81%
      versus 11.11%, respectively, P < 0.001). CONCLUSIONS: The results of this study
      suggest that the value of TPMT genotyping before thiopurine therapy is limited in
      Chinese patients with IBD, considering the low sensitivity of predicting
      leucopenia, and that phenotyping is a more cost-effective tool that can be
      successfully used in patients. The coadministration of 5-aminosalicylates results
      in a high frequency of leucopenia in patients receiving azathioprine or 6
      mercaptopurine.

PMID- 23149443
TI  - The pharmacokinetic profile of intravenous paracetamol in adult patients
      undergoing major abdominal surgery.
AB  - BACKGROUND: Intravenous (IV) paracetamol is commonly used in the postoperative
      period for the treatment of mild to moderate pain. The main pathways for
      paracetamol metabolism are glucuronidation, sulfation, and oxidation, accounting
      for approximately 55%, 30%, and 10% of urinary metabolites, respectively. The aim
      of this study was to describe the pharmacokinetics of IV paracetamol and its
      metabolites in adult patients after major abdominal surgery. METHODS: Twenty
      patients were given 1 g of paracetamol by IV infusion at induction of anesthesia
      (Interval 1) and every 6 hours thereafter, with the final dose given at 48-72
      hours (Interval 2). Plasma and urine samples were collected for up to 8 hours
      after infusion for both intervals. The samples were analyzed by high-performance
      liquid chromatography to determine the amount of paracetamol and its metabolites.
      The data were modeled in Phoenix WinNonlin using a user-defined ASCII parent
      metabolite model with linear disposition, to obtain the estimates for volume of
      distribution, metabolic and urinary clearance. RESULTS: Mean (95% confidence
      interval) metabolic clearance to paracetamol glucuronide increased from 0.06
      (0.05-0.08) to 0.14 (0.11-0.18) L . h-1 . kg-1, P value <0.001 and urinary
      clearance increased from 0.08 (0.07-0.09) to 0.14 (0.10-0.17) L . h-1 . kg-1, P
      value 0.002. The mean (95% confidence interval) volume of distribution of
      paracetamol increased from 0.17 (0.12-0.21) to 0.43 (0.27-0.59) L . kg-1, P value
      0.032. CONCLUSIONS: After major abdominal surgery, there were apparent increases
      in the metabolic conversion to paracetamol glucuronide and its urinary clearance
      suggesting potential induction of paracetamol glucuronidation.

PMID- 23149444
TI  - Negative predictive value of IL28B, SLC28A2, and CYP27B1 SNPs and low RBV plasma
      exposure for therapeutic response to PEG/IFN-RBV treatment.
AB  - OBJECTIVES: The response rate to treatment of chronic hepatitis C virus-genotype
      1 and 4 infections was recently found to be strongly influenced by many
      polymorphisms. The aim of our study was to carry out an integrated analysis of
      the effects of polymorphisms and ribavirin (RBV) plasma exposure on outcome.
      METHODS: The retrospective analysis included 174 patients. IL28B, CYP27B1,
      SLC29A1, SLC28A3, and SLC28A2 polymorphisms were genotyped and tested for
      association with sustained virological response. The impact of RBV plasma
      exposure during the first 3 months of therapy on outcome was also investigated.
      RESULTS: Considering patients infected by hepatitis C virus-1/4, 3 polymorphisms
      (IL28B rs8099917TT, CYP27B1 rs4646536TT, and CNT2 rs11854484TT) were associated
      with sustained virological response. The number of negative variant allele and
      low RBV exposure were correlated to percentage increasing to therapy failure,
      suggesting some degree of cumulative effect of the 4 factors. A cutoff of 2.5
      MUg/mL of RBV was found to be associated with outcome (area under ROC [AUROC]
      curve = 0.64, sensitivity = 55.0%, and specificity = 71.2%, P = 0.020). In
      multivariate logistic regression analyses, each variant allele and RBV plasma
      exposure cutoff were independently associated with outcome. CONCLUSIONS: In this
      study, we found that additional polymorphisms and RBV plasma exposure are also
      able to influence the achievement of response. Regardless of the magnitude of RBV
      pharmacokinetic exposure, the negative predictive value of the polymorphisms here
      investigated is much stronger than the positive one.

PMID- 23149445
TI  - In vivo knockdown of GAD67 in the amygdala disrupts fear extinction and the
      anxiolytic-like effect of diazepam in mice.
AB  - In mammals, gamma-aminobutyric acid (GABA) transmission in the amygdala is
      particularly important for controlling levels of fear and anxiety. Most GABA
      synthesis in the brain is catalyzed in inhibitory neurons from L-glutamic acid by
      the enzyme glutamic acid decarboxylase 67 (GAD67). In the current study, we
      sought to examine the acquisition and extinction of conditioned fear in mice with
      knocked down expression of the GABA synthesizing enzyme GAD67 in the amygdala
      using a lentiviral-based (LV) RNA interference strategy to locally induce loss-of
      function. In vitro experiments revealed that our LV-siRNA-GAD67 construct
      diminished the expression of GAD67 as determined with western blot and
      fluorescent immunocytochemical analyses. In vivo experiments, in which male
      C57BL/6J mice received bilateral amygdala microinjections, revealed that LV-siRNA
      GAD67 injections produce significant inhibition of endogenous GAD67 when compared
      with control injections. In contrast, no significant changes in GAD65 expression
      were detected in the amygdala, validating the specificity of LV knockdown.
      Behavioral experiments showed that LV knockdown of GAD67 results in a deficit in
      the extinction, but not the acquisition or retention, of fear as measured by
      conditioned freezing. GAD67 knockdown did not affect baseline locomotion or basal
      measures of anxiety as measured in open field apparatus. However, diminished
      GAD67 in the amygdala blunted the anxiolytic-like effect of diazepam (1.5 mg kg(
      1)) as measured in the elevated plus maze. Together, these studies suggest that
      of GABAergic transmission in amygdala mediates the inhibition of conditioned fear
      and the anxiolytic-like effect of diazepam in adult mice.

PMID- 23149446
TI  - Maternal interpersonal affiliation is associated with adolescents' brain
      structure and reward processing.
AB  - Considerable animal and human research has been dedicated to the effects of
      parenting on structural brain development, focusing on hippocampal and prefrontal
      areas. Conversely, although functional imaging studies suggest that the neural
      reward circuitry is involved in parental affection, little is known about
      mothers' interpersonal qualities in relation to their children's brain structure
      and function. Moreover, gender differences concerning the effect of maternal
      qualities have rarely been investigated systematically. In 63 adolescents, we
      assessed structural and functional magnetic resonance imaging as well as
      interpersonal affiliation in their mothers. This allowed us to associate maternal
      affiliation with gray matter density and neural responses during different phases
      of the well-established Monetary Incentive Delay task. Maternal affiliation was
      positively associated with hippocampal and orbitofrontal gray matter density.
      Moreover, in the feedback of reward hit as compared with reward miss, an
      association with caudate activation was found. Although no significant gender
      effects were observed in these associations, during reward feedback as compared
      with baseline, maternal affiliation was significantly associated with ventral
      striatal and caudate activation only in females. Our findings demonstrate that
      maternal interpersonal affiliation is related to alterations in both the brain
      structure and reward-related activation in healthy adolescents. Importantly, the
      pattern is in line with typical findings in depression and post-traumatic stress
      disorder, suggesting that a lack of maternal affiliation might have a role in the
      genesis of mental disorders.

PMID- 23149447
TI  - Early accumulation of intracellular fibrillar oligomers and late congophilic
      amyloid angiopathy in mice expressing the Osaka intra-Abeta APP mutation.
AB  - Pathogenic amyloid-beta peptide precursor (APP) mutations clustered around
      position 693 of APP-position 22 of the Abeta sequence--are commonly associated
      with congophilic amyloid angiopathy (CAA) and intracerebral hemorrhages. In
      contrast, the Osaka (E693Delta) intra-Abeta APP mutation shows a recessive
      pattern of inheritance that leads to AD-like dementia despite low brain amyloid
      on in vivo positron emission tomography imaging. Here, we investigated the
      effects of the Osaka APP mutation on Abeta accumulation and deposition in vivo
      using a newly generated APP transgenic mouse model (E22DeltaAbeta) expressing the
      Osaka mutation together with the Swedish (K670N/M671L) double mutation.
      E22DeltaAbeta mice exhibited reduced alpha-processing of APP and early
      accumulation of intraneuronal fibrillar Abeta oligomers associated with cognitive
      deficits. In line with our in vitro findings that recombinant E22Delta-mutated
      Abeta peptides form amyloid fibrils, aged E22DeltaAbeta mice showed extracellular
      CAA deposits in leptomeningeal cerebellar and cortical vessels. In vitro results
      from thioflavin T aggregation assays with recombinant Abeta peptides revealed a
      yet unknown antiamyloidogenic property of the E693Delta mutation in the
      heterozygous state and an inhibitory effect of E22Delta Abeta42 on E22Delta
      Abeta40 fibrillogenesis. Moreover, E22Delta Abeta42 showed a unique aggregation
      kinetics lacking exponential fibril growth and poor seeding effects on wild-type
      Abeta aggregation. These results provide a possible explanation for the recessive
      trait of inheritance of the Osaka APP mutation and the apparent lack of amyloid
      deposition in E693Delta mutation carriers.

PMID- 23149448
TI  - Multi-locus genome-wide association analysis supports the role of glutamatergic
      synaptic transmission in the etiology of major depressive disorder.
AB  - Major depressive disorder (MDD) is a common psychiatric illness characterized by
      low mood and loss of interest in pleasurable activities. Despite years of effort,
      recent genome-wide association studies (GWAS) have identified few susceptibility
      variants or genes that are robustly associated with MDD. Standard single-SNP
      (single nucleotide polymorphism)-based GWAS analysis typically has limited power
      to deal with the extensive heterogeneity and substantial polygenic contribution
      of individually weak genetic effects underlying the pathogenesis of MDD. Here, we
      report an alternative, gene-set-based association analysis of MDD in an effort to
      identify groups of biologically related genetic variants that are involved in the
      same molecular function or cellular processes and exhibit a significant level of
      aggregated association with MDD. In particular, we used a text-mining-based data
      analysis to prioritize candidate gene sets implicated in MDD and conducted a
      multi-locus association analysis to look for enriched signals of nominally
      associated MDD susceptibility loci within each of the gene sets. Our primary
      analysis is based on the meta-analysis of three large MDD GWAS data sets (total
      N=4346 cases and 4430 controls). After correction for multiple testing, we found
      that genes involved in glutamatergic synaptic neurotransmission were
      significantly associated with MDD (set-based association P=6.9 * 10(-4)). This
      result is consistent with previous studies that support a role of the
      glutamatergic system in synaptic plasticity and MDD and support the potential
      utility of targeting glutamatergic neurotransmission in the treatment of MDD.

PMID- 23149449
TI  - Responder and nonresponder patients exhibit different peripheral transcriptional
      signatures during major depressive episode.
AB  - To date, it remains impossible to guarantee that short-term treatment given to a
      patient suffering from a major depressive episode (MDE) will improve long-term
      efficacy. Objective biological measurements and biomarkers that could help in
      predicting the clinical evolution of MDE are still warranted. To better
      understand the reason nearly half of MDE patients respond poorly to current
      antidepressive treatments, we examined the gene expression profile of peripheral
      blood samples collected from 16 severe MDE patients and 13 matched controls.
      Using a naturalistic and longitudinal design, we ascertained mRNA and microRNA
      (miRNA) expression at baseline, 2 and 8 weeks later. On a genome-wide scale, we
      detected transcripts with roles in various biological processes as significantly
      dysregulated between MDE patients and controls, notably those involved in
      nucleotide binding and chromatin assembly. We also established putative
      interactions between dysregulated mRNAs and miRNAs that may contribute to MDE
      physiopathology. We selected a set of mRNA candidates for quantitative reverse
      transcriptase PCR (RT-qPCR) to validate that the transcriptional signatures
      observed in responders is different from nonresponders. Furthermore, we
      identified a combination of four mRNAs (PPT1, TNF, IL1B and HIST1H1E) that could
      be predictive of treatment response. Altogether, these results highlight the
      importance of studies investigating the tight relationship between peripheral
      transcriptional changes and the dynamic clinical progression of MDE patients to
      provide biomarkers of MDE evolution and prognosis.

PMID- 23149450
TI  - Meta-analysis of genome-wide association studies for panic disorder in the
      Japanese population.
AB  - Panic disorder (PD) is a moderately heritable anxiety disorder whose pathogenesis
      is not well understood. Due to the lack of power in previous association studies,
      genes that are truly associated with PD might not be detected. In this study, we
      conducted a genome-wide association study (GWAS) in two independent data sets
      using the Affymetrix Mapping 500K Array or Genome-Wide Human SNP Array 6.0. We
      obtained imputed genotypes for each GWAS and performed a meta-analysis of two
      GWAS data sets (718 cases and 1717 controls). For follow-up, 12 single-nucleotide
      polymorphisms (SNPs) were tested in 329 cases and 861 controls. Gene ontology
      enrichment and candidate gene analyses were conducted using the GWAS or meta
      analysis results. We also applied the polygenic score analysis to our two GWAS
      samples to test the hypothesis of polygenic components contributing to PD.
      Although genome-wide significant SNPs were not detected in either of the GWAS nor
      the meta-analysis, suggestive associations were observed in several loci such as
      BDKRB2 (P=1.3 * 10(-5), odds ratio=1.31). Among previous candidate genes,
      supportive evidence for association of NPY5R with PD was obtained (gene-wise
      corrected P=6.4 * 10(-4)). Polygenic scores calculated from weakly associated
      SNPs (P<0.3 and 0.4) in the discovery sample were significantly associated with
      PD status in the target sample in both directions (sample I to sample II and vice
      versa) (P<0.05). Our findings suggest that large sets of common variants of small
      effects collectively account for risk of PD.

PMID- 23149451
TI  - Psychiatric symptoms correlate with metabolic indices in the hippocampus and
      cingulate in patients with mitochondrial disorders.
AB  - There is increasing recognition that mitochondrial dysfunction may have a
      critical role in the pathophysiology of major psychiatric illnesses. Patients
      with mitochondrial disorders offer a unique window through which we can begin to
      understand the association between psychiatric symptoms and mitochondrial
      dysfunction in vivo. Using proton magnetic resonance spectroscopy ((1)H-MRS), we
      investigated metabolic indices in mitochondrial patients in regions of the brain
      that have been implicated in psychiatric illness: the caudate, cingulate cortex
      and hippocampus. In all, 15 patients with mitochondrial disorders and 15 age- and
      sex-matched controls underwent a comprehensive psychiatric assessment, including
      the administration of standardized psychiatric rating scales, followed by single
      voxel (1)H-MRS of the caudate, cingulate cortex and hippocampus to measure N
      acetyl aspartate (NAA), creatine (Cr), glycerophosphocholine (GPC), myoinositol
      and glutamate+glutamine (Glx). Pearson's correlation coefficients were used to
      determine correlations between metabolites and the psychiatric rating scales.
      Anxiety symptoms in these patients correlated with higher GPC, Glx, myoinositol
      and Cr in the hippocampus. Impaired level of function as a result of psychiatric
      symptoms correlated with higher Glx and GPC in the cingulate cortex. In summary,
      we found remarkably consistent, and statistically significant, correlations
      between anxiety and metabolic indices in the hippocampus in patients with
      mitochondrial disorders, while overall impairment of functioning due to
      psychiatric symptoms correlated with metabolic markers in the cingulate cortex.
      These findings lend support to the notion that mitochondrial dysfunction in
      specific brain regions can give rise to psychiatric symptoms. In particular, they
      suggest that metabolic processes in the hippocampus may have an important role in
      the neurobiology of anxiety.

PMID- 23149452
TI  - Stem cell therapy: social recognition recovery in a FASD model.
AB  - To better understand the cellular pathogenetic mechanisms of fetal alcohol
      spectrum disorder (FASD) and the therapeutic benefit of stem cell treatment, we
      exposed pregnant rats to ethanol followed by intravenous administration of neural
      stem cells (NSCs) complexed with atelocollagen to the new born rats and studied
      recovery of GABAergic interneuron numbers and synaptic protein density in the
      anterior cingulate cortex, hippocampus and amygdala. Prenatal ethanol exposure
      reduced both parvalbumin-positive phenotype of GABAergic interneurons and
      postsynaptic density protein 95 levels in these areas. Intravenous NSC treatment
      reversed these reductions. Furthermore, treatment with NSCs reversed impaired
      memory/cognitive function and social interaction behavior. These experiments
      underscore an important role for synaptic remodeling and GABAergic interneuron
      genesis in the pathophysiology and treatment of FASD and highlight the
      therapeutic potential for intravenous NSC administration in FASD utilizing
      atelocollagen.

PMID- 23149453
TI  - Association of eHealth literacy with colorectal cancer knowledge and screening
      practice among internet users in Japan.
AB  - BACKGROUND: In rapidly developing Internet-user societies, eHealth literacy has
      become important in promoting wellness. Although previous studies have observed
      that poor health literacy is associated with less knowledge and screening
      practice of colorectal cancer (CRC), little is known about whether eHealth
      literacy is associated with these variables. OBJECTIVE: The present study
      examined associations between eHealth literacy, knowledge of CRC, and CRC
      screening practices. METHODS: Data were analyzed for 2970 Japanese adults (men,
      49.9%; mean age+/-SD, 39.7+/-10.9 years) who responded to an Internet-based cross
      sectional survey. Knowledge of the definition of CRC, its risk factors and
      screening practice, previous experience of CRC screening, score on the Japanese
      version of the eHEALS (J-eHEALS), sociodemographic attributes (sex, age, marital
      status, educational attainment, and household income level), and frequency of
      Internet usage were obtained. Sociodemographic attributes and frequency of
      Internet usage were used as control variables in the multiple regression and
      logistic regression models. RESULTS: eHealth literacy was positively associated
      with CRC knowledge (beta=.116, <.001), when the covariables of both eHealth
      literacy and CRC knowledge were used in the multiple regression model. Moreover,
      after controlling for sociodemographic factors, which were significantly
      associated with eHealth literacy and CRC screening practice, an increase of 1
      point in the eHEALS score signified that participants were 1.03 times (95%
      CI=1.01-1.05) more likely to undergo CRC screening. CONCLUSIONS: Internet users
      with high eHealth literacy are more likely to have knowledge and previous
      screening practice related to CRC compared to those with low eHealth literacy.

PMID- 23149454
TI  - Genetic influences on social dominance: cow wars.

PMID- 23149455
TI  - Transcriptome de novo assembly from next-generation sequencing and comparative
      analyses in the hexaploid salt marsh species Spartina maritima and Spartina
      alterniflora (Poaceae).
AB  - Spartina species have a critical ecological role in salt marshes and represent an
      excellent system to investigate recurrent polyploid speciation. Using the 454 GS
      FLX pyrosequencer, we assembled and annotated the first reference transcriptome
      (from roots and leaves) for two related hexaploid Spartina species that hybridize
      in Western Europe, the East American invasive Spartina alterniflora and the Euro
      African S. maritima. The de novo read assembly generated 38 478 consensus
      sequences and 99% found an annotation using Poaceae databases, representing a
      total of 16 753 non-redundant genes. Spartina expressed sequence tags were mapped
      onto the Sorghum bicolor genome, where they were distributed among the
      subtelomeric arms of the 10 S. bicolor chromosomes, with high gene density
      correlation. Normalization of the complementary DNA library improved the number
      of annotated genes. Ecologically relevant genes were identified among GO
      biological function categories in salt and heavy metal stress response, C4
      photosynthesis and in lignin and cellulose metabolism. Expression of some of
      these genes had been found to be altered by hybridization and genome duplication
      in a previous microarray-based study in Spartina. As these species are hexaploid,
      up to three duplicated homoeologs may be expected per locus. When analyzing
      sequence polymorphism at four different loci in S. maritima and S. alterniflora,
      we found up to four haplotypes per locus, suggesting the presence of two
      expressed homoeologous sequences with one or two allelic variants each. This
      reference transcriptome will allow analysis of specific Spartina genes of
      ecological or evolutionary interest, estimation of homoeologous gene expression
      variation using RNA-seq and further gene expression evolution analyses in natural
      populations.

PMID- 23149456
TI  - The heritability of metabolic profiles in newborn twins.
AB  - Identifying genetic and metabolic biomarkers in neonates has the potential to
      improve diagnosis and treatment of common complex neonatal diseases, and
      potentially lead to risk assessment and preventative measures for common
      adulthood illnesses such as diabetes and cardiovascular disease. There is a
      wealth of information on using fatty acid, amino acid and organic acid metabolite
      profiles to identify rare inherited congenital diseases through newborn
      screening, but little is known about these metabolic profiles in the context of
      the 'healthy' newborn. Recent studies have implicated many of the amino acid and
      fatty acid metabolites utilized in newborn screening in common complex adult
      diseases such as cardiovascular disease, insulin resistance and obesity. To
      determine the heritability of metabolic profiles in newborns, we examined 381
      twin pairs obtained from the Iowa Neonatal Metabolic Screening Program.
      Heritability was estimated using multilevel mixed-effects linear regression
      adjusting for gestational age, gender, weight and age at time of sample
      collection. The highest heritability was for short-chain acylcarnitines,
      specifically C4 (h2=0.66, P=2 * 10-16), C4-DC (h2=0.83, P<10-16) and C5 (h2=0.61,
      P=1 * 10-9). Thyroid stimulating hormone (h2=0.58, P=2 * 10-5) and immunoreactive
      trypsinogen (h2=0.52, P=3 * 10-9) also have a strong genetic component. This is
      direct evidence for a strong genetic contribution to the metabolic profile at
      birth and that newborn screening data can be utilized for studying the genetic
      regulation of many clinically relevant metabolites.

PMID- 23149457
TI  - Transgressive physiological and transcriptomic responses to light stress in
      allopolyploid Glycine dolichocarpa (Leguminosae).
AB  - Allopolyploidy is often associated with increased photosynthetic capacity as well
      as enhanced stress tolerance. Excess light is a ubiquitous plant stress
      associated with photosynthetic light harvesting. We show that under chronic
      excess light, the capacity for non-photochemical quenching (NPQ(max)), a
      photoprotective mechanism, was higher in a recently formed natural allotetraploid
      (Glycine dolichocarpa, designated 'T2') than in its diploid progenitors (G.
      tomentella, 'D3'; and G. syndetika, 'D4'). This enhancement in NPQ(max) was due
      to an increase in energy-dependent quenching (qE) relative to D3, combined with
      an increase in zeaxanthin-dependent quenching (qZ) relative to D4. To explore the
      genetic basis for this phenotype, we profiled D3, D4 and T2 leaf transcriptomes
      and found that T2 overexpressed genes of the water-water cycle relative to both
      diploid progenitors, as well as genes involved in cyclic electron flow around
      photosystem I (CEF-PSI) and the xanthophyll cycle, relative to D4. Xanthophyll
      pigments have critical roles in NPQ, and the water-water cycle and CEF-PSI are
      non-photosynthetic electron transport pathways believed to facilitate NPQ
      formation. In the absence of CO(2), T2 also exhibited greater quantum yield of
      photosystem II than either diploid, indicating a greater capacity for non
      photosynthetic electron transport. We postulate that, relative to its diploid
      progenitors, T2 is able to achieve higher NPQ(max) due to an increase in
      xanthophyll pigments coupled with enhanced electron flow through the water-water
      cycle and CEF-PSI.

PMID- 23149458
TI  - Bayesian methods for estimating GEBVs of threshold traits.
AB  - Estimation of genomic breeding values is the key step in genomic selection (GS).
      Many methods have been proposed for continuous traits, but methods for threshold
      traits are still scarce. Here we introduced threshold model to the framework of
      GS, and specifically, we extended the three Bayesian methods BayesA, BayesB and
      BayesCpi on the basis of threshold model for estimating genomic breeding values
      of threshold traits, and the extended methods are correspondingly termed BayesTA,
      BayesTB and BayesTCpi. Computing procedures of the three BayesT methods using
      Markov Chain Monte Carlo algorithm were derived. A simulation study was performed
      to investigate the benefit of the presented methods in accuracy with the genomic
      estimated breeding values (GEBVs) for threshold traits. Factors affecting the
      performance of the three BayesT methods were addressed. As expected, the three
      BayesT methods generally performed better than the corresponding normal Bayesian
      methods, in particular when the number of phenotypic categories was small. In the
      standard scenario (number of categories=2, incidence=30%, number of quantitative
      trait loci=50, h2 = 0.3), the accuracies were improved by 30.4%, 2.4%, and 5.7%
      points, respectively. In most scenarios, BayesTB and BayesTCpi generated similar
      accuracies and both performed better than BayesTA. In conclusion, our work proved
      that threshold model fits well for predicting GEBVs of threshold traits, and
      BayesTCpi is supposed to be the method of choice for GS of threshold traits.

PMID- 23149459
TI  - Polyploidy and its effect on evolutionary success: old questions revisited with
      new tools.
AB  - Polyploidy, the condition of possessing more than two complete genomes in a cell,
      has intrigued biologists for almost a century. Polyploidy is found in many plants
      and some animal species and today we know that polyploidy has had a role in the
      evolution of all angiosperms. Despite its widespread occurrence, the direct
      effect of polyploidy on evolutionary success of a species is still largely
      unknown. Over the years many attractive hypotheses have been proposed in an
      attempt to assign functionality to the increased content of a duplicated genome.
      Among these hypotheses are the proposal that genome doubling confers distinct
      advantages to a polyploid and that these advantages allow polyploids to thrive in
      environments that pose challenges to the polyploid's diploid progenitors. This
      article revisits these long-standing questions and explores how the integration
      of recent genomic developments with ecological, physiological and evolutionary
      perspectives has contributed to addressing unresolved problems about the role of
      polyploidy. Although unsatisfactory, the current conclusion has to be that
      despite significant progress, there still isn't enough information to
      unequivocally answer many unresolved questions about cause and effect of
      polyploidy on evolutionary success of a species. There is, however, reason to
      believe that the increasingly integrative approaches discussed here should allow
      us in the future to make more direct connections between the effects of
      polyploidy on the genome and the responses this condition elicits from the
      organism living in its natural environment.

PMID- 23149460
TI  - Rapid, habitat-related evolution of land snail colour morphs on reclaimed land.
AB  - I made use of the known dates of reclamation (and of afforestations) in the
      IJsselmeerpolders in The Netherlands to assess evolutionary adaptation in Cepaea
      nemoralis. At 12 localities (three in each polder), I sampled a total of 4390
      adult individuals in paired open and shaded habitats, on average 233 m apart, and
      scored these for genetic shell colour polymorphisms. The results show (highly)
      significant differentiation at most localities, although the genes involved
      differed per locality. Overall, though, populations in shaded habitats had
      evolved towards darker shells than those in adjacent open habitats, whereas a
      'Cain & Sheppard' diagram (proportion yellow shells plotted against 'effectively
      unbanded' shells) failed to reveal a clear pattern. This might suggest that
      thermal selection is more important than visual selection in generating this
      pattern. Trait differentiation, regardless of whether they were plotted against
      polder age or habitat age, showed a linear increase of differentiation with time,
      corresponding to a mean rate of trait evolution of 15-31 kilodarwin. In
      conclusion, C. nemoralis is capable of rapid and considerable evolutionary
      differentiation over 1-25 snail generations, though equilibrium may be reached
      only at longer time scales.

PMID- 23149462
TI  - All UK trains should carry automated external defibrillators (AEDs).

PMID- 23149461
TI  - Deviation from a preoperative surgical and anaesthetic care plan is associated
      with increased risk of adverse intraoperative events in major abdominal surgery.
AB  - BACKGROUND: Perioperative coordination facilitates team communication and
      planning. The aim of this study was to determine how often deviation from
      predicted surgical conditions and a pre-established anaesthetic care plan in
      major abdominal surgery occurred, and whether this was associated with an
      increase in adverse clinical events. METHODS: In this prospective observational
      study, weekly preoperative interdisciplinary team meetings were conducted
      according to a joint care plan checklist in a tertiary care centre in France. Any
      discordance with preoperative predictions and deviation from the care plan were
      noted. A link to the incidence of predetermined adverse intraoperative events was
      investigated. RESULTS: Intraoperative adverse clinical events (ACEs) occurred in
      15 % of all cases and were associated with postoperative complications [relative
      risk (RR) = 1.5; 95 % confidence interval (1.1; 2.2)]. Quality of prediction of
      surgical procedural items was modest, with one in five to six items not correctly
      predicted. Discordant surgical prediction was associated with an increased
      incidence of ACE. Deviation from the anaesthetic care plan occurred in around 13
      %, which was more frequent when surgical prediction was inaccurate (RR > 3) and
      independently associated with ACE (odds ratio 6). CONCLUSION: Surgery was more
      difficult than expected in up to one out of five cases. In a similar proportion,
      disagreement between preoperative care plans and observed clinical management was
      independently associated with an increased risk of adverse clinical events.

PMID- 23149463
TI  - Relatedness between host species and genotype of beak and feather disease virus
      suggesting possible interspecies cross infection during bird trade.
AB  - Beak and feather disease virus (BFDV) is a causative agent of psittacine beak and
      feather disease (PBFD), which shows a characteristic feather disorder in
      psittacine birds. In the present study, the subclinical infection rate of PBFD in
      imported and domestically bred psittacine birds was investigated by polymerase
      chain reaction. As a result, 126 of 402 birds (31.3%) were found to be BFDV
      positive. The DNA sequences of the part of open reading frame (ORF) C1 were
      determined for 16 BFDV-positive randomly selected samples. One of 16 samples was
      found to have a mixed infection, and 5 different BFDV sequences were obtained
      from a single African grey parrot. In phylogenic analysis, almost BFDV sequences
      included in each genetic cluster of phylogenic tree belonged to the same
      psittacine subfamily. BFDV derived from African grey parrot was closely related
      to the BFDV derived from cockatoos by way of exception. The natural habitat of
      the African grey parrot and cockatoos is different, and therefore, the
      possibility of interspecies cross infection through the bird trade is suggested
      from the exceptional BFDV sequences.

PMID- 23149464
TI  - Patient and tumor characteristics associated with breast cancer recurrence after
      complete pathological response to neoadjuvant chemotherapy.
AB  - Breast cancer patients whose tumors achieve a pathological complete response
      (pCR) with neoadjuvant chemotherapy have a prognosis which is better than that
      predicted for the stage of their disease. However, within this subgroup of
      patients, recurrences have been observed. We sought to examine factors associated
      with recurrence in a population of breast cancer patients who achieved a pCR with
      neoadjuvant chemotherapy. A retrospective chart review was conducted of all
      patients with unilateral breast cancer treated with neoadjuvant chemotherapy from
      January 1, 2000 to December 31, 2010 at one comprehensive cancer center. A pCR
      was defined as no residual invasive cancer in the breast in the surgical specimen
      following neoadjuvant therapy. Recurrence was defined as visceral or bony
      reappearance of cancer after completion of all therapy. Of 818 patients who
      completed neoadjuvant chemotherapy, 144 (17.6 %) had pCR; six with bilateral
      breast cancer were excluded from further analysis. The mean time to follow-up was
      47.2 months. Among the 138 patients with unilateral breast cancer, there were 14
      recurrences (10.1 %). Using a binary multiple logistic regression model,
      examining types of chemotherapy and surgery, race, lymph node assessment, and
      lymph node status, breast cancer side, triple-negative status, and radiation
      receipt, only African-American patients (OR: 5.827, 95 % CI: 1.280-26.525; p =
      0.023) were more likely to develop distant recurrence. The mean time to
      recurrence was 31.9 months. In our study, race was the only independent predictor
      of recurrence after achieving pCR with neoadjuvant chemotherapy. The reasons for
      this observation require further study.

PMID- 23149466
TI  - Placental weight and mortality in premenopausal breast cancer by tumor
      characteristics.
AB  - Placental weight may be regarded as an indirect marker of hormone exposures
      during pregnancy. There is epidemiological evidence that breast cancer mortality
      in premenopausal women increases with placental weight in the most recent
      pregnancy. We investigated if this association differs by tumor characteristics,
      including expression of estrogen and progesterone receptors. In a Swedish
      population-based cohort, we followed 1,067 women with premenopausal breast cancer
      diagnosed from 1992 to 2006. Using Cox regression models, we estimated hazard
      ratios for the association between placental weight and risk of premenopausal
      breast cancer mortality. In stratified analyses, we estimated mortality risks in
      subjects with different tumor stages, estrogen receptor (ER) or progesterone
      receptor (PR) status. Compared with women with placental weight less than 600 g,
      women with a placental weight between 600 and 699 g were at a 50 % increased risk
      of mortality, however, not significant change in risk was observed for women with
      placental weight >= 700 g. Mortality risks associated with higher placental
      weight were more pronounced among ER(-) and PR(-) breast cancer tumors, where
      both a placental weight 600-699 g and >= 700 g were associated with a more than
      doubled mortality risks compared with tumors among women with placental weight
      less than 600 g. Moreover, stratified analyses for joint receptor status revealed
      that a consistent increased mortality risk by placental weight was only apparent
      in women with ER(-)/PR(-) breast cancer. The increased mortality risk in
      premenopausal breast cancer associated with higher placental weight was most
      pronounced among ER(-) and PR(-) tumors.

PMID- 23149467
TI  - Comparison of the results and complications of palmar and dorsal miniinvasive
      approaches in the surgery of scaphoid fractures. A prospective randomized study.
AB  - AIMS: To compare the functional results and complications associated with palmar
      percutaneous and dorsal limited approaches in the surgical treatment of
      nondisplaced or minimally displaced scaphoid fractures type B2. METHODS: A total
      of 76 patients with acute nondisplaced or minimally displaced type B2 scaphoid
      fractures were included in a prospective randomised study. The assignment
      patients to groups according to type of operative approach was based on
      systematic sampling. Clinical follow-up, X-ray or CT imaging were performed at
      four, eight and twelve weeks and one year after the surgery. Patient satisfaction
      and the results of DASH form were evaluated as well. The differences were
      statistically tested. RESULTS: We found significantly better flexion and grip
      strength in the group of palmar percutaneous aprroach during the follow-up
      examination at eight weeks after the surgery. Significantly better flexion of the
      same group persisted at twelve-week follow-up examination. No differences in
      results or complications were statistically significant up to one year follow up.
      CONCLUSIONS: We found no advantage to the palmar percutaneous approach in the
      treatment of nondisplaced and minimally displaced scaphoid fractures type B2
      compared to dorsal limited approach.

PMID- 23149465
TI  - Trends in co-prescribing of antidepressants and tamoxifen among women with breast
      cancer, 2004-2010.
AB  - Nearly a decade ago, researchers identified a potential interaction between
      tamoxifen and strong CYP2D6 inhibitors, including several frequently used
      antidepressants. Based on evidence available at that time, a United States Food
      and Drug Administration advisory committee recommended tamoxifen's label be
      changed in October 2006, noting that postmenopausal women with estrogen receptor
      positive breast cancer who are poor CYP2D6 metabolizers by genotype or drug
      interactions may be at increased risk of cancer recurrence. The impact of
      accumulating drug risk information on antidepressant use is unknown. We conducted
      a retrospective, longitudinal cohort study of 13,205 women aged 50-95 with breast
      cancer initiating tamoxifen between July 2004 and December 2009. We evaluated
      trends in strong, moderate, and weak CYP2D6-inhibitor antidepressants and
      tamoxifen co-prescribing and factors associated with ongoing strong inhibitor
      use. A propensity score matched control group (aromatase inhibitor initiators)
      was used to estimate changes in co-prescribing, accounting for secular trends. In
      each month, approximately 24 % of tamoxifen and aromatase inhibitor users were
      prescribed antidepressants. Among women using tamoxifen and antidepressants, 34 %
      used strong inhibitors between 2004 and 2006 versus 15 % in 2010. Strong
      inhibitor use decreased more among tamoxifen users than aromatase inhibitor users
      (difference-in-differences [DD] -0.09; 95 % confidence interval [CI] -0.15, 
      0.03). Weak inhibitor use increased among tamoxifen users from 32 % between 2004
      and 2006 to 52 % in 2010, more rapidly than among aromatase inhibitor users (DD
      0.15; CI 0.08, 0.23). The factor most strongly associated with strong inhibitor
      and tamoxifen co-prescribing after 2006 was prior strong inhibitor use (RR 4.73;
      CI 3.62-6.18). In conclusion, there were substantial declines in strong CYP2D6
      inhibitor use among tamoxifen users following dissemination of information
      suggesting a potential for increased risk with co-prescribing. Whether patients
      and providers will continue to avoid strong inhibitor antidepressants is yet to
      be seen, but clinicians appear to be responsive to drug interaction risk
      information in this setting.

PMID- 23149468
TI  - The role of steroids in the development of post-partum mental disorders.
AB  - BACKGROUND: Unfavorable post-partum changes to mental well-being affect more than
      half of all women, and are a risk to the health of both mother and baby. Their
      effects place strains on health and social systems. Currently, no generally
      accepted theory exists of the causes and mechanisms of post-partum mental
      disorders. METHODS: Literature search up to 2012, using PubMed and search words:
      neuroactive steroids, post-partum mental disorders, depression, corticotropin
      releasing hormone and estrogens. RESULTS: There are several theories for post
      partum depression. One is that autoimmune diseases are involved. Others revolve
      around genes responsible or that lead to increased disposition to the disorder.
      It is likely however that the process is associated with the separation of the
      placenta and the fetal zone of fetal adrenal gland, the main sources of
      corticotropin-releasing hormone and sexual and neuroactive steroids during
      pregnancy, and the ability of the receptor system to adapt to these changes. The
      central nervous system is able to produce neurosteroids, but the drop in levels
      of peripheral steroids likely leads to a sudden deficit in neuroinhibitory
      steroids modulating ionotropic receptors in the brain. CONCLUSIONS: Post-partum
      depression is a multifactorial disease with unknown etiology. It is probably
      associated with sudden changes in the production of hormones influencing the
      nervous system, and on the other hand the ability of the receptor system to adapt
      to these changes. When the relative changes in concentrations of hormones, rather
      than their absolute levels, is likely more important.

PMID- 23149469
TI  - Detection of diketopiperazine and pyrrolnitrin, compounds with anti-Pythium
      insidiosum activity, in a Pseudomonas stutzeri environmental strain.
AB  - AIMS: Screening of bacterial flora for strains producing metabolites with
      inhibitory effects on the human pathogenic oomycete Pythium insidiosum.
      Separation and characterization of extracts from Pseudomonas stutzeri with anti
      Pythium inhibitory activity. Search for genes with anti-Pythium effect within the
      genome of P. stutzeri. METHODS: A total of 88 bacterial strains were isolated
      from water resources in northeastern Thailand. Two screening methods were used to
      establish their inhibitory effects on P. insidiosum. One strain, P. stutzeri
      ST1302 was randomly chosen, and the extract with anti-P. insidiosum activity was
      fractionated and subfractionated using liquid column chromatography and purified
      by thin layer chromatography. The chemical structure of purified fractions was
      determined by Fourier transform infrared spectroscopy, nuclear magnetic resonance
      and mass spectrometry. Further, search for genes involved in the anti-Pythium
      activity (phenazine-1-carboxylic acid, 2,4-diacetylphloroglucinol, pyoluteorin
      and pyrrolnitrin) was undertaken in this P. stutzeri strain using primers
      described in the literature. RESULTS: Anti-P. insidiosum activity was detected in
      16 isolates (18.2%). In P. stutzeri ST1302, a subfraction labeled PYK7 exhibited
      strong activity against this oomycete. It was assigned to the diketopiperazines
      as cyclo(D-Pro-L-Val). In the search for genes, one gene region was successfully
      amplified. This corresponded to pyrrolnitrin. The results suggest the possibility
      of using the related metabolites against P. insidiosum. This is the first report
      on the inhibitory effects of P. stutzeri against this oomycete. The results may
      contribute to the development of antimicrobial drugs/probiotics against
      pythiosis.

PMID- 23149470
TI  - Reactions of a tungsten-germylyne complex with alcohols and arylaldehydes.
AB  - A germylyne complex Cp*(CO)2W=GeC(SiMe3)3 (1) reacted with alcohols to give
      simple nucleophilic addition products, while 1 reacted with two molecules of
      arylaldehydes consecutively to give base-stabilised alkoxy(germylene) complexes
      via C-H bond activation and hydrogermylation.

PMID- 23149472
TI  - It is a great pleasure to write this editorial, having taken over from Roger
      Butlin, who has done such an outstanding job for Heredity over the last 4 years.
      Introduction.

PMID- 23149471
TI  - Ex vivo assessment of contractility, fatigability and alternans in isolated
      skeletal muscles.
AB  - Described here is a method to measure contractility of isolated skeletal muscles.
      Parameters such as muscle force, muscle power, contractile kinetics,
      fatigability, and recovery after fatigue can be obtained to assess specific
      aspects of the excitation-contraction coupling (ECC) process such as
      excitability, contractile machinery and Ca(2+) handling ability. This method
      removes the nerve and blood supply and focuses on the isolated skeletal muscle
      itself. We routinely use this method to identify genetic components that alter
      the contractile property of skeletal muscle though modulating Ca(2+) signaling
      pathways. Here, we describe a newly identified skeletal muscle phenotype, i.e.,
      mechanic alternans, as an example of the various and rich information that can be
      obtained using the in vitro muscle contractility assay. Combination of this assay
      with single cell assays, genetic approaches and biochemistry assays can provide
      important insights into the mechanisms of ECC in skeletal muscle.

PMID- 23149473
TI  - Chemical communication in the honey bee scarab pest Oplostomus haroldi: role of
      (Z)-9-pentacosene.
AB  - Oplostomus haroldi Witte belongs to a unique genus of afro-tropical scarabs that
      have associations with honey bee colonies, from which they derive vital
      nutrients. Although the attributes of the honey bee nest impose barriers to
      communication among nest invaders, this beetle still is able to detect
      conspecific mates for reproduction. Here, we show, through behavioral studies,
      that cuticular lipids serve as mate discrimination cues in this beetle. We
      observed five steps during mating: arrestment, alignment, mounting, and
      copulation, and a post-copulatory stage, lasting ~40-70 % of the total mating
      duration, that suggested mate guarding. Chemical analysis identified the same
      nine straight-chain alkanes (C(23)-C(31)), six methyl-branched alkanes (6), and
      five mono-unsaturated alkenes in the cuticular lipids of both sexes. Methyl
      alkanes constituted the major component (46 %) of male cuticular lipids, while
      mono-unsaturated alkenes were most abundant (53 %) in females. (Z)-9-Pentacosene
      was twice as abundant in females than in males, and ~20 fold more concentrated in
      beetles than in worker bees. In mating assays, (Z)-9-pentacosene elicited
      arrestment, alignment, and mounting, but not copulation, by male beetles. These
      results represent the first evidence of a contact sex pheromone in a scarab
      beetle. Such contact pheromones may be an essential, cryptic mechanism for
      arthropods associated with eusocial insects.

PMID- 23149474
TI  - A plea for an independent holistic anaesthesia delivery system.

PMID- 23149475
TI  - Excellent outcomes of simultaneous pancreas kidney transplantation in patients
      from rural and urban Australia: a national service experience.
AB  - BACKGROUND: Simultaneous pancreas and kidney (SPK) transplantation is performed
      to restore normoglycemia and renal function in patients with type 1 diabetes
      mellitus and end-stage renal failure. The National Pancreas Transplant Unit
      (NPTU) in Sydney provides a service to a population spread across 7.4 million km.
      We aimed to see if SPK transplantation outcomes differed between recipients from
      metropolitan (M) centers and those from nonmetropolitan (NM) regions. METHODS:
      Using a prospectively collected database, patient and graft survival were
      analyzed. Patients were categorized according to region of residence and by
      distance from the NPTU. RESULTS: Between January 2001 and May 2010, 165 patients
      underwent first-time SPK transplantation at the NPTU. There were 126 M and 39 NM
      recipients. Median distance from the NPTU was 732 km for donors (range, 0-3930
      km) and 887 km for recipients (range, 1-4114 km). Median follow-up was 5.2 years
      (range, 1.1-10.3 years). Actuarial 5-year patient survival was 94% in M and 95%
      in NM groups. At 5 years, non-death-censored pancreas graft survival was 75% and
      82% among M and NM patients, respectively, while kidney allograft survival was
      88% in M and 92% in NM groups. There was no significant difference in patient and
      graft survival between groups. Distance of donor and recipient from the NPTU did
      not influence graft or patient survival. CONCLUSIONS: SPK transplantation can be
      performed with excellent outcomes at a national center with a vast catchment
      area, irrespective of donor or recipient location.

PMID- 23149477
TI  - Factors predictive of medication nonadherence after renal transplantation:  a
      French observational study.
AB  - BACKGROUND: There have been few prospective studies on the natural history of
      nonadherence (NA) in kidney transplant recipients (KTRs) over time. The objective
      of this study was to prospectively evaluate the rate of and risk factors for NA
      in a French cohort of KTRs. METHOD: A total of 312 KTRs from eight French
      transplantation centers were included in this prospective, noninterventional
      cohort study. A computer-learning software package (the Organ Transplant
      Information System) was made available to all patients. RESULTS: Using the four
      item Morisky scale, we showed that 17.3%, 24.1%, 30.7%, and 34.6% of patients
      were nonadherent at posttransplant month 3 (M3), M6, M12, and M24, respectively.
      Young age was predictive of NA at M6, M12, and M24. Surprisingly, simple
      treatment regimens including a small number of doses per day and a small number
      of tablets per day were associated with NA at M3 and M12, respectively. Other
      factors predictive of NA included failure to use the Organ Transplant Information
      System software package at M6 and patient reports of adverse events at M12 and
      M24. Importantly, we observed that physicians underestimated the prevalence of
      adverse events when compared to patient self-reporting. CONCLUSION: Our observed
      rate of medication NA in France is consistent with rates reported in previous
      studies. We found variability in NA risk factors over time as well as an
      unexpected risk factor (simple treatment regimens). These findings will be useful
      in developing effective adherence-promoting interventions.

PMID- 23149478
TI  - Despite the best intentions cancer is transmissible by transplantation.

PMID- 23149479
TI  - The Nobel Prize-winning work of Ralph Steinman (1943-2011) and its relevance to
      transplantation.

PMID- 23149480
TI  - Fast frequency sweeping in resonance-tracking SPM for high-resolution AFAM and
      PFM imaging.
AB  - A new resonance-tracking (RT) method using fast frequency sweeping excitation was
      developed for quantitative scanning probe microscopy (SPM) imaging. This method
      allows quantitative imaging of elastic properties and ferroelectrical domains
      with nanoscale resolution at high data acquisition rates. It consists of a
      commercial AFM system combined with a high-frequency lock-in amplifier, a
      programmed function generator and a fast data acquisition card. The resonance
      tracking method was applied to the atomic force acoustic microscopy (AFAM) and to
      the piezoresponse force microscopy (PFM) modes. Plots of amplitude versus time
      and phase versus time for resonant spectra working with different sweeping
      frequencies were obtained to evaluate the response speed of the lock-in
      amplifier. It was proved that this resonance-tracking method allows suitable
      spectral acquisition at a rate of about 5 ms/pixel, which is useful for SPM
      imaging in a practical scanning time. In order to demonstrate the system
      performance, images of RT-AFAM for TiN films and RT-PFM for GeTe are shown.

PMID- 23149481
TI  - Self-healing of bended WS2 nanotubes and its effect on the nanotube's properties.
AB  - Individual WS(2) nanotubes (NTs) were bended and released in-situ inside a
      transmission electron microscope. Kinks appeared in the NTs suddenly during the
      bending process. Shell distortion, shell breaking and rotation of broken shells
      were observed in these kinks. Spontaneous self-healing and focused electron beam
      assisted healing of the structure were observed after the load was removed. More
      importantly, the strength and electrical conductivity of the NTs were also
      restored to their original level when the structure recovered.

PMID- 23149482
TI  - Development of a sandwich enzyme-linked immunosorbent assay to detect and measure
      serum levels of canine ferritin.
AB  - We established a homologous sandwich enzyme-linked immunosorbent assay (ELISA) to
      measure serum levels of canine ferritin. Our assay uses a rabbit anti-canine
      heart ferritin polyclonal antibody, and canine heart ferritin as a standard.
      Serum ferritin concentration in healthy dogs (n=163) was 789 +/- 284 ng/ml (mean
      +/- standard deviation), a value higher than reported previously. Confidence
      levels relating to repeatability, dilution and recovery for this method were
      high. Therefore, we believe our developed sandwich ELISA will be effective in
      evaluating serum levels of canine ferritin.

PMID- 23149483
TI  - Specific molecular detection and characterization of Anaplasma marginale in
      Mongolian cattle.
AB  - Anaplasma marginale is an etiologic agent of bovine anaplasmosis. This study
      aimed to molecularly detect and characterize A. marginale that is prevalent in
      Mongolian cattle populations. A highly specific and sensitive nested PCR (nPCR)
      method based on the Msp5 gene was developed to detect A. marginale (Msp5 nPCR).
      The method detected A. marginale from the positive DNA samples obtained from
      different countries, while no amplicons were observed from DNA samples of several
      other bovine blood pathogens tested. The detection limit of Msp5 nPCR was
      determined to be 2 copies/MUl. The method was tested against field blood DNA
      samples prepared from 300 Mongolian cattle in 2010. Results indicated a
      prevalence rate of 8.7% (26 of 300). On the other hand, partial DNA fragments of
      an Anaplasma sp. closely related to A. ovis (with 95.0% identity) were detected
      using a different nPCR method based on groEL gene. The phylogenetic analyses
      based on the Msp5, groEL and 16S rRNA genes demonstrated that A. marginale
      isolates in Mongolia were not divergent from the isolates distributed in other
      countries. The present study successfully established a new nPCR assay that can
      detect A. marginale, and reported the first molecular detection and
      characterization of A. marginale and an Anaplasma sp. closely related to A. ovis
      in Mongolian cattle populations.

PMID- 23149484
TI  - Simple and sensitive method for measurement of metoclopramide in cattle plasma by
      LC-MS/MS using a multimode chromatography.
AB  - A quantitative assay method using LC/ESI-MS/MS for simultaneous determination of
      MCP in cattle plasma was developed and validated. Chromatographic separation was
      carried out using a multimode column (2 * 150 mm, 3 MUm) with gradient elution
      (0.05% formic acid/methanol with 0.05% formic acid). MCP and levosulpiride
      (internal standard) were analyzed in the precursor/product ion pair of m/z
      300.1/226.9 and 342.0/112.0, respectively. Linear calibration curves were
      obtained in the range of 2.5-500 ng/ml (R(2)>0.999) with a lower limit of
      quantification of 0.05 ng/ml. Mean recoveries were 96-103%, and the coefficient
      of variation was less than 6.5%. Plasma MCP concentrations after intravenous
      administration at 0.4 mg/kg to 12 cattle were determined by the LC-MS/MS method.

PMID- 23149486
TI  - Why have the breast surgeons been referred to the GMC?

PMID- 23149485
TI  - Integrated bioinformatic and targeted deletion analyses of the SRS gene
      superfamily identify SRS29C as a negative regulator of Toxoplasma virulence.
AB  - The Toxoplasma gondii SRS gene superfamily is structurally related to SRS29B
      (formerly SAG1), a surface adhesin that binds host cells and stimulates host
      immunity. Comparative genomic analyses of three Toxoplasma strains identified 182
      SRS genes distributed across 14 chromosomes at 57 genomic loci. Eight distinct
      SRS subfamilies were resolved. A core 69 functional gene orthologs were
      identified, and strain-specific expansions and pseudogenization were common. Gene
      expression profiling demonstrated differential expression of SRS genes in a
      developmental-stage- and strain-specific fashion and identified nine SRS genes as
      priority targets for gene deletion among the tissue-encysting coccidia. A
      Deltasag1 sag2A mutant was significantly attenuated in murine acute virulence and
      showed upregulated SRS29C (formerly SRS2) expression. Transgenic overexpression
      of SRS29C in the virulent RH parent was similarly attenuated. Together, these
      findings reveal SRS29C to be an important regulator of acute virulence in mice
      and demonstrate the power of integrated genomic analysis to guide experimental
      investigations. IMPORTANCE: Parasitic species employ large gene families to
      subvert host immunity to enable pathogen colonization and cause disease.
      Toxoplasma gondii contains a large surface coat gene superfamily that encodes
      adhesins and virulence factors that facilitate infection in susceptible hosts. We
      generated an integrated bioinformatic resource to predict which genes from within
      this 182-gene superfamily of adhesin-encoding genes play an essential role in the
      host-pathogen interaction. Targeted gene deletion experiments with predicted
      candidate surface antigens identified SRS29C as an important negative regulator
      of acute virulence in murine models of Toxoplasma infection. Our integrated
      computational and experimental approach provides a comprehensive framework, or
      road map, for the assembly and discovery of additional key pathogenesis genes
      contained within other large surface coat gene superfamilies from a broad array
      of eukaryotic pathogens.

PMID- 23149487
TI  - P2X receptor stimulation amplifies complement-induced haemolysis.
AB  - Activation of the complement system evokes cell damage by insertion of membrane
      attack complexes, which constitute the basis of the pathogenesis of various
      haemolytic disorders. Recently, we found that haemolysis caused by other types of
      membrane pore-forming proteins such as alpha-haemolysin (HlyA) from Escherichia
      coli, alpha-toxin from Staphylococcus aureus and leukotoxin from Aggregatibacter
      actinomycetemcomitans inflict their cytotoxic effects through P2 receptor
      activation. Here we show that similar to haemolysis induced by HlyA, leukotoxin
      and alpha-toxin, complement-induced haemolysis is amplified through ATP release
      and subsequent P2 receptor activation. Similar results were found both in murine,
      sensitised ovine and human erythrocytes, with either human plasma or guinea pig
      serum as complement donors. Non-selective P2 antagonists (PPADS and suramin)
      concentration-dependently inhibited complement-induced haemolysis. More specific
      P2 receptor antagonists imply that P2X1 and P2X7 are the main receptors involved
      in this response. Moreover, complement activation produces a sustained increase
      in [Ca(2+)]i, which initially triggers significant erythrocyte shrinkage, most
      likely mediated by KCa3.1-dependent K(+) efflux. These results indicate that
      complement, similar to HlyA and alpha-toxin, requires purinergic signalling for
      full haemolysis and that activation of erythrocyte volume regulation protracts
      the process. This finding points to several new pathways to interfere with
      haemolytic diseases and implies that P2 receptor antagonists potentially can be
      used to prevent intravascular haemolysis.

PMID- 23149488
TI  - Frequency-dependent mitochondrial Ca(2+) accumulation regulates ATP synthesis in
      pancreatic beta cells.
AB  - Pancreatic beta cells respond to increases in glucose concentration with enhanced
      metabolism, the closure of ATP-sensitive K(+) channels and electrical spiking.
      The latter results in oscillatory Ca(2+) influx through voltage-gated Ca(2+)
      channels and the activation of insulin release. The relationship between changes
      in cytosolic and mitochondrial free calcium concentration ([Ca(2+)]cyt and
      [Ca(2+)]mit, respectively) during these cycles is poorly understood. Importantly,
      the activation of Ca(2+)-sensitive intramitochondrial dehydrogenases, occurring
      alongside the stimulation of ATP consumption required for Ca(2+) pumping and
      other processes, may exert complex effects on cytosolic ATP/ADP ratios and hence
      insulin secretion. To explore the relationship between these parameters in single
      primary beta cells, we have deployed cytosolic (Fura red, Indo1) or green
      fluorescent protein-based recombinant-targeted (Pericam, 2mt8RP for mitochondria;
      D4ER for the ER) probes for Ca(2+) and cytosolic ATP/ADP (Perceval) alongside
      patch-clamp electrophysiology. We demonstrate that: (1) blockade of mitochondrial
      Ca(2+) uptake by shRNA-mediated silencing of the uniporter MCU attenuates glucose
      and essentially blocks tolbutamide-stimulated, insulin secretion; (2) during
      electrical stimulation, mitochondria decode cytosolic Ca(2+) oscillation
      frequency as stable increases in [Ca(2+)]mit and cytosolic ATP/ADP; (3)
      mitochondrial Ca(2+) uptake rates remained constant between individual spikes,
      arguing against activity-dependent regulation ("plasticity") and (4) the
      relationship between [Ca(2+)]cyt and [Ca(2+)]mit is essentially unaffected by
      changes in endoplasmic reticulum Ca(2+) ([Ca(2+)]ER). Our findings thus highlight
      new aspects of Ca(2+) signalling in beta cells of relevance to the actions of
      both glucose and sulphonylureas.

PMID- 23149490
TI  - A special issue on the renin-angiotensin system.

PMID- 23149489
TI  - Ablation of smooth muscle caldesmon affects the relaxation kinetics of arterial
      muscle.
AB  - Smooth muscle caldesmon (h-CaD) is an actin- and myosin-binding protein that
      reversibly inhibits the actomyosin ATPase activity in vitro. To test the function
      of h-CaD in vivo, we eliminated its expression in mice. The h-CaD-null animals
      appeared normal and fertile, although the litter size was smaller. Tissues from
      the homozygotes lacked h-CaD and exhibited upregulation of the non-muscle
      isoform, l-CaD, in visceral, but not vascular tonic smooth muscles. While the
      Ca(2+) sensitivity of force generation of h-CaD-deficient smooth muscle remained
      largely unchanged, the kinetic behavior during relaxation in arteries was
      different. Both intact and permeabilized arterial smooth muscle tissues from the
      knockout animals relaxed more slowly than those of the wild type. Since this
      difference occurred after myosin dephosphorylation was complete, the kinetic
      effect most likely resulted from slower detachment of unphosphorylated
      crossbridges. Detailed analyses revealed that the apparently slower relaxation of
      h-CaD-null smooth muscle was due to an increase in the amplitude of a slower
      component of the biphasic tension decay. While the identity of this slower
      process has not been unequivocally determined, we propose it reflects a thin
      filament state that elicits fewer re-attached crossbridges. Our finding that h
      CaD modulates the rate of smooth muscle relaxation clearly supports a role in the
      control of vascular tone.

PMID- 23149491
TI  - [Prevalence of mental disorders in multimodal therapy of chronic back pain].
AB  - Because of its biopsychosocial factors chronic back pain is often resistant to
      unimodal therapy regimes. Multimodal pain programs are a promising therapy option
      in the management of chronic pain as they focus on functional restoration. The
      aim of the study was to evaluate the prevalence of psychopathology in patients
      with chronic back pain. The study included 127 patients suffering from chronic
      back pain in multimodal inpatient pain therapy who were assessed by a
      psychologist. A retrospective analysis was performed focusing on the
      psychological diagnoses. Further factors investigated were age, gender, numeric
      rating scale (NRS) pain intensity at the beginning and end of the program,
      hospital anxiety and depression scale (HADS), further psychological treatment
      recommendations and migration background. Fisher's exact test was performed to
      calculate the significance in the different subgroups. The results showed that
      there was a high prevalence of depression, anxiety disorders and adjustment
      disorders in patients with chronic back pain. In this cohort the prevalence of
      depression and anxiety disorders was significantly higher than the estimated
      prevalence of the normal German population.

PMID- 23149493
TI  - The impact of body mass index and central obesity on the spino-pelvic parameters:
      a correlation study.
AB  - INTRODUCTION: Obesity is an increasing problem of epidemic proportion, and it is
      associated with various musculoskeletal disorders, including impairment of the
      spine. However, the relationship between obesity and spino-pelvic parameters
      remains to date unsupported by an objective measurement of the mechanical
      behavior of the spino-pelvic parameters depending on body mass index (BMI) and
      the presence of central obesity. Such analysis may provide a deeper understanding
      of this relationship. PURPOSE: To assess whether BMI and central obesity are
      associated with modifications on spino-pelvic parameters and determine if exists
      any correlation between BMI and obesity with the type of lumbar lordosis (LL).
      METHODS: A cross-sectional study with 200 participants was conducted. Parameters
      measured were LL, pelvic tilt, sacral slope, and pelvic incidence (PI), using
      lumbosacral radiographs in lateral view. Subjects were classified depending on
      BMI. In a secondary analysis, the subjects were categorized into two groups
      depending on the presence or not of elevated abdominal circumference. The
      categorical variables were compared using Chi-square test, and the mean values
      were compared using ANOVA and student t test. A Spearman correlation test was
      used to analyze the correlation between BMI categories and LL types. RESULTS:
      From the total of participants, there were 51 (25.5 %) normal weight subjects, 93
      (46.5 %) overweight, and 56 (28 %) obese individuals. The spino-pelvic parameters
      among these groups are practically equal. The correlation between the different
      BMI categories and LL types is poor 0.06 (P = 0.34). In a secondary analysis,
      grouping the participants in obese and non-obese, the results showed that obesity
      is modestly positively associated with increasing of spino-pelvic parameters
      values, in particular with PI (P = 0.078). The comparison made between the
      presence or not of central obesity, interestingly did not show significant
      differences. CONCLUSIONS: Despite the results did not reach statistically
      significant differences, the results indicate that the obese spine is slightly
      different from the non-obese spine. Therefore, this relationship deserves future
      attention.

PMID- 23149494
TI  - Laterality of cervical disc herniation.
AB  - PURPOSE: Cervical disc herniation (CDH) is found more frequently at the lower
      cervical spine than at the upper or middle level. However, there is scarcity of
      data about the laterality of CDH. The aim of this study is to detect the
      laterality of CDH. METHODS: We retrospectively evaluated preoperative computed
      tomography myelograms and magnetic resonance images of 75 cases of CDH who
      underwent single level anterior cervical discectomy and fusion at C4-5, C5-6, or
      C6-7 levels from 2008 to 2010 in our institute. Statistical analyses were
      performed using the Chi-square test. RESULTS: Eleven cases were found at C4-5
      level, 42 cases at C5-6 level, and 22 cases at C6-7 level. At C4-5 level, CDH was
      recognized at the right side in 2 cases, at the left side in 2 cases, and at the
      center in 7 cases. At C5-6 level, CDH was found at the right side in 20 cases and
      at the left side in 22 cases. At C6-7 level, CDH was found at the right side in 3
      cases and at the left side in 19 cases with significantly high frequency of left
      sided CDH (p < 0.025). CONCLUSIONS: In this study, it was revealed that the left
      sided CDH was more frequent than the right-sided CDH at C6-7 level.

PMID- 23149495
TI  - Diagnosis, treatment, and outcome of giant-cell myocarditis in the era of
      combined immunosuppression.
AB  - BACKGROUND: Giant-cell myocarditis often escapes diagnosis until autopsy or
      transplantation and has defied proper treatment trials for its rarity and deadly
      behavior. Current therapy rests on multiple-drug immunosuppression but its
      prognostic influence remains poorly known. We set out to analyze (1) our
      experience in diagnosing giant-cell myocarditis and (2) the outcome of patients
      on combined immunosuppression. METHODS AND RESULTS: We reviewed the histories,
      diagnostic procedures, details of treatment, and outcome of 32 consecutive
      patients with histologically verified giant-cell myocarditis treated in our
      hospital since 1991. Twenty-six patients (81%) were diagnosed by endomyocardial
      or surgical biopsies and 6 at autopsy or post-transplantation. Twenty-eight (88%)
      patients underwent endomyocardial biopsy. The sensitivity of transvenous
      endomyocardial biopsy increased from 68% (19/28 patients) to 93% (26/28) after up
      to 2 repeat procedures. The 26 biopsy-diagnosed patients were treated with
      combined immunosuppression (2-4 drugs) including cyclosporine in 20 patients. The
      Kaplan-Meier estimates of transplant-free survival from symptom onset were 69% at
      1 year, 58% at 2 years, and 52% at 5 years. Of the transplant-free survivors,
      10/17 (59%) experienced sustained ventricular tachyarrhythmias during follow-up
      and 3 received intracardiac defibrillator shocks for ventricular tachycardia or
      fibrillation. CONCLUSIONS: Repeat endomyocardial biopsies are frequently needed
      to diagnose giant-cell myocarditis. On contemporary immunosuppession, two thirds
      of patients reach a partial clinical remission characterized by freedom from
      severe heart failure and need of transplantation but continuing proneness to
      ventricular tachyarrhythmias.

PMID- 23149496
TI  - Statement regarding the pre and post market assessment of durable, implantable
      ventricular assist devices in the United States: executive summary.
AB  - The incorporation of complex medical device technologies into clinical practice
      is governed by critical oversight of the US Food and Drug Administration. This
      regulatory process requires a judicious balance between assuring safety and
      efficacy, while providing efficient review to facilitate access to innovative
      therapies. Recent contrasting views of the regulatory process have emphasized the
      difficulties in obtaining an optimal balance. Mechanical circulatory support has
      evolved to become an important therapy for patients with advanced heart failure
      with the advent of more durable, implantable ventricular assist devices. The
      regulatory oversight of these new technologies has been difficult owing to the
      complexities of these devices, associated adverse event profile, and severity of
      illness of the intended patient population. Maintaining a regulatory environment
      to foster efficient introduction of safe and effective technologies is critical
      to the success of ventricular assist device therapy and the health of patients
      with advanced heart failure. Physicians representing key surgical and cardiology
      societies, and representatives from the Food and Drug Administration, National
      Heart, Lung, and Blood Institute, Centers for Medicare and Medicaid Services,
      Interagency Registry of Mechanically Assisted Circulatory Support, and industry
      partners gathered to discuss relevant issues regarding the current regulatory
      environment assessing ventricular assist devices. The goal of the meeting was to
      explore innovative ways to foster the introduction of technologically advanced,
      safe, and effective ventricular assist devices. The following summary reflects
      opinions and conclusions endorsed by The Society of Thoracic Surgeons, American
      Association for Thoracic Surgery, American Heart Association, Heart Failure
      Society of America, International Society for Heart and Lung Transplantation, and
      the Interagency Registry of Mechanically Assisted Circulatory Support.

PMID- 23149497
TI  - Statement regarding the pre and post market assessment of durable, implantable
      ventricular assist devices in the United States.
AB  - The incorporation of complex medical device technologies into clinical practice
      is governed by critical oversight of the US Food and Drug Administration. This
      regulatory process requires a judicious balance between assuring safety and
      efficacy, while providing efficient review to facilitate access to innovative
      therapies. Recent contrasting views of the regulatory process have emphasized the
      difficulties in obtaining an optimal balance. Mechanical circulatory support has
      evolved to become an important therapy for patients who have advanced heart
      failure with the advent of more durable, implantable ventricular assist devices.
      The regulatory oversight of these new technologies has been difficult owing to
      the complexities of these devices, associated adverse event profile, and severity
      of illness of the intended patient population. Maintaining a regulatory
      environment to foster efficient introduction of safe and effective technologies
      is critical to the success of ventricular assist device therapy and the health of
      patients with advanced heart failure. Physicians representing key surgical and
      cardiology societies, and representatives from the Food and Drug Administration,
      National Heart, Lung, and Blood Institute, Centers for Medicare and Medicaid
      Services, Interagency Registry of Mechanically Assisted Circulatory Support, and
      industry partners gathered to discuss relevant issues regarding the current
      regulatory environment assessing ventricular assist devices. The goal of the
      meeting was to explore innovative ways to foster the introduction of
      technologically advanced, safe, and effective ventricular assist devices. The
      following summary reflects opinions and conclusions endorsed by The Society of
      Thoracic Surgeons, American Association for Thoracic Surgery, American Heart
      Association, Heart Failure Society of America, International Society for Heart
      and Lung Transplantation, and Interagency Registry of Mechanically Assisted
      Circulatory Support.

PMID- 23149498
TI  - Prospective cohort study of metabolic risk factors and gastric adenocarcinoma
      risk in the Metabolic Syndrome and Cancer Project (Me-Can).
AB  - PURPOSE: Little is known about the association between the metabolic syndrome
      (MetS) and the risk of gastric adenocarcinoma. The aim of this study was to
      investigate whether metabolic risk factors, together or combined, were associated
      with the risk of gastric adenocarcinoma. METHODS: The Metabolic Syndrome and
      Cancer Project (Me-Can) is a pooling of prospective cohorts in Austria, Norway,
      and Sweden with information on blood pressure, lipids, glucose, and BMI available
      in 578,700 individuals. Cox proportional hazards analysis was used to calculate
      hazard ratio (HR) of gastric adenocarcinoma using metabolic risk factors
      categorized into quintiles and transformed into z-scores (with mean = 0 and SD =
      1). The standardized sum of all z-scores created a composite MetS score. RESULTS:
      In total, 1,210 incident cases of gastric adenocarcinoma were identified. Glucose
      was significantly associated with the risk of gastric adenocarcinoma [calibrated
      HR 1.58 (1.14-2.20) per one unit increment in z-score] in women. There was a
      statistically significant association between triglycerides and risk of gastric
      adenocarcinoma per mmol increment in triglycerides [HR 1.20 (1.06-1.36) per mmol]
      but not for the adjusted z-score in women. There were no significant association
      between any metabolic factors and gastric cancer among men. The composite MetS
      score was associated with the risk of gastric adenocarcinoma in women [HR 1.18
      (1.00-1.38) per one unit increment in z-score] but not in men. CONCLUSIONS:
      Glucose and high levels of the composite MetS score were associated with an
      increased risk of gastric adenocarcinoma in women but not in men.

PMID- 23149500
TI  - Synthesis and structure of a hydrogenated zinc hemiporphyrazine.
AB  - Palladium-catalyzed hydrogenation of an octahedral zinc trans-ditriflate
      hemiporphyrazine "HpH2Zn(OTf)2" furnishes a new macrocycle "HpH6Zn(OTf)2". This
      reaction is fully reversible upon heating in nitrobenzene, and the conversion is
      easily monitored by changes in color and fluorescence properties. The reversible
      cycling between these molecules may find future applications in hemiporphyrazine
      based catalysts and/or hydrogen storage devices.

PMID- 23149501
TI  - A viscoelastic model of blood capillary extension and regression: derivation,
      analysis, and simulation.
AB  - This work studies a fundamental problem in blood capillary growth: how the cell
      proliferation or death induces the stress response and the capillary extension or
      regression. We develop a one-dimensional viscoelastic model of blood capillary
      extension/regression under nonlinear friction with surroundings, analyze its
      solution properties, and simulate various growth patterns in angiogenesis. The
      mathematical model treats the cell density as the growth pressure eliciting a
      viscoelastic response from the cells, which again induces extension or regression
      of the capillary. Nonlinear analysis captures two cases when the biologically
      meaningful solution exists: (1) the cell density decreases from root to tip,
      which may occur in vessel regression; (2) the cell density is time-independent
      and is of small variation along the capillary, which may occur in capillary
      extension without proliferation. The linear analysis with perturbation in cell
      density due to proliferation or death predicts the global biological solution
      exists provided the change in cell density is sufficiently slow in time. Examples
      with blow-ups are captured by numerical approximations and the global solutions
      are recovered by slow growth processes, which validate the linear analysis
      theory. Numerical simulations demonstrate this model can reproduce angiogenesis
      experiments under several biological conditions including blood vessel extension
      without proliferation and blood vessel regression. 

PMID- 23149503
TI  - The success rate of narrow body implants used for supporting immediate
      provisional restorations:  a pilot feasibility study.
AB  - BACKGROUND: Implants were first designed to be used in the reconstruction of
      edentulous mandibles. However, with the technological advancement, enormous
      changes were made to improve the implant design and surface characteristics
      leading to the wide use of implants in the replacement of missing teeth. During
      the transition from an edentulous span to a fixed prosthesis, narrow body
      implants (NBIs) have been proposed to enhance patient comfort and function.
      Therefore, this study was aimed at investigating the survival and success rates
      of NBIs used for supporting immediately nonfunctional loaded provisional fixed
      partial denture (PFPD). METHODS: Either 2.2- or 2.4-mm-diameter dental implants
      were placed transmucosally into the edentulous ridges of 10 partially edentulous
      patients. PFPD of self-cured bis-acryl composite material were made using either
      a vacuform template chairside or a relined prefabricated PFPD. Occlusal
      adjustments were made to ensure that there was no functional loading on the
      provisional restorations before they were secured onto the transitional implants.
      RESULTS: At 1 year, the implant success and survival rates were 38.7% and 93.5%,
      respectively, with a mean percentage of bone loss of 9.46% (0%-40%) and a mean
      bone loss of 1.19 mm (range: 0-3.5 mm). CONCLUSIONS: With a favorable implant
      survival rate, the use of NBIs to support provisional restorations seemed to be a
      feasible treatment option. In addition, there is merit for research on the long
      term use of NBIs-supported final prostheses.

PMID- 23149502
TI  - Early bone healing around 2 different experimental, HA grit-blasted, and dual
      acid-etched titanium implant surfaces. A pilot study in rabbits.
AB  - PURPOSE: To compare early bone healing around different experimental titanium
      implant surfaces and to evaluate the role of a calcium phosphate-coated implant
      surface because it relates to bone-implant contact (BIC). METHODS: An
      experimental hydroxyapatite (HA) grit-blasted and dual acid-etched titanium
      surface (BAE-1) was compared to an experimental HA grit-blasted and dual acid
      etched surface treated with nanometer-scale crystals of HA (BAE-2). Both
      experimental implant surfaces were implanted onto the tibias of 4 New Zealand
      white rabbits. The animals were killed at 1,6, 21, and 90 days after the implant
      surgery. Descriptive histology was performed at the healing responses of both
      implant surfaces. Quantitative morphology assessment provided measurements of
      BIC, number of bone multicellular units (BMUs), average penetration of BMUs, and
      maximum penetration of BMUs that were manually made using imaging computer
      software. RESULT: The overall BIC for the BAE-2 implant was higher than that for
      the BAE-1 implant at 21 days of healing. However, there was no significant
      difference at 90 days of healing. CONCLUSION: It is concluded from this animal
      pilot study that the bioactive BAE-2 implant surface provided a better BIC with
      healthy bone remodeling at 21 days of healing.

PMID- 23149504
TI  - Implant primary stability determined by resonance frequency analysis: 
      correlation with insertion torque, histologic bone volume, and torsional
      stability at 6 weeks.
AB  - OBJECTIVE: To determine if resonance frequency analysis (RFA) correlated with
      insertion torque (IT), bone volume (BV), and clinical osseointegration at 6
      weeks. MATERIALS AND METHODS: For 18 patients, BV was evaluated histologically by
      retrieving bone core biopsies before placement of 40 dental implants. Peak IT was
      recorded at implant placement, and RFA values (implant stability quotient [ISQ])
      were noted at baseline, 3 weeks, and 6 weeks. Osseointegration was evaluated at 6
      weeks when torquing abutments to 30 N. ISQ values were correlated with IT, BV and
      abutment torquing results. Data were statistically analyzed. RESULTS: ISQ values
      significantly decreased at 3 weeks and increased at 6 weeks. There was a
      significant positive correlation between BV and ISQ at baseline and at 3 weeks,
      but not at 6 weeks, and between ISQ and jaw location, implant diameter and IT at
      baseline, 3 weeks, and 6 weeks. There was a significant correlation between
      spinning/painful implants during abutment torquing and low ISQ, low BV, and low
      IT values. CONCLUSION: Correlations between BV and IT values, and ISQ suggest
      that RFA may indicate primary implant stability. BV, IT, and ISQ values may
      anticipate the degree of osseointegration at 6 weeks.

PMID- 23149505
TI  - Minimally invasive sinus augmentation using ultrasonic piezoelectric vibration
      and hydraulic pressure:  a multicenter retrospective study.
AB  - PURPOSE: The purpose of this study was to evaluate the success rate of implants
      and vertical bone gain of edentulous posterior maxilla using ultrasonic
      piezoelectric vibration and hydraulic pressure, namely the hydrodynamic
      piezoelectric internal sinus elevation (HPISE) technique through a crestal
      approach. MATERIALS AND METHODS: A total of 250 maxillary sinuses were augmented
      using HPISE and 353 implants (averaging 11.8 mm in length and 4.5 mm in
      diameter), with 12 different systems, were placed simultaneously with or without
      additional bone grafting. Plain radiograms and cone beam computed tomograms were
      taken in all patients to evaluate sinus augmentation. RESULTS: Membrane
      perforation was recorded at 10 of the 353 implant sites. The perforation rate was
      2.83%. The total success rate of implantation was 97.2% after an average of 69.3
      weeks of loading. CONCLUSION: The crestally approached sinus augmentation using
      ultrasonic piezoelectric vibration and hydraulic pressure is an additional method
      of maxillary sinus augmentation.

PMID- 23149507
TI  - Incidental genitourinary findings on obstetrics/gynecology ultrasound.
AB  - Ultrasound is the standard-of-care imaging modality for initial imaging in
      obstetrics and gynecology. Given the close proximity of the genitourinary system
      to the uterus and adnexa, it is not surprising that these studies can result in
      the discovery of incidental genitourinary findings such as ureterocele, ectopic
      ureter, bladder mass, ureteral stones, cystitis, bladder diverticulum, and pelvic
      kidney. Recognition of the etiology of these findings is important for
      appropriate diagnosis and, at times, patient care. Many of these findings are
      truly incidental and clinically unimportant but other times can be related to the
      patient's chief complaint.

PMID- 23149508
TI  - Two-/three-dimensional transperineal sonography of complicated tape and mesh
      implants.
AB  - Transperineal sonography (TPS) affords dynamic evaluation of suburethral slings
      using tensionless vaginal tape and mesh implants used to treat complications
      associated with surgical procedures of the pelvic floor. This review describes
      and illustrates the TPS findings in postoperative complications such as recurrent
      prolapse, cystocele, enterocele, and rectocele. The potential use of live 3
      dimensional TPS to delineate the dynamics aspects of pelvic floor disorder is
      also mentioned.

PMID- 23149509
TI  - Contrast-enhanced ultrasound-guided radiofrequency ablation of renal tumors.
AB  - Radiofrequency ablation of renal masses is an increasing utilized technique for
      treatment of malignant renal neoplasia. Image guidance is needed for
      radiofrequency ablation needle placement, as well as evaluation of the size of
      the ablation burn and determination if any residual tumor is present. Contrast
      enhanced ultrasound is unique in its ability to provide image guidance for this
      procedure. In addition to improved visualization of the mass for needle
      placement, the contrast can be injected multiple times during the procedure to
      evaluate the size of the ablation burn and the presence of residual tumor, if
      any. This article describes how to use contrast-enhanced ultrasound to perform
      radiofrequency ablation of renal masses. Pictorial cases are used to demonstrate
      the robustness of this technique.

PMID- 23149510
TI  - Uterine ultrasound findings after radiofrequency endometrial ablation:
      correlation with symptoms.
AB  - OBJECTIVES: To determine pelvic ultrasound characteristics in women after
      radiofrequency endometrial ablation (EA) and evaluate the association of those
      characteristics with symptoms and the need for subsequent therapeutic
      intervention. METHODS: This retrospective cohort study evaluated patients who
      underwent transvaginal pelvic ultrasound after radiofrequency EA between July 3,
      2006, and November 13, 2009. The presence or absence of postablation symptoms
      (pelvic pain or vaginal bleeding) at the time of ultrasound defined the 2 groups.
      Two radiologists evaluated 17 ultrasound parameters. Demographic, clinical, and
      ultrasound characteristics were compared between symptomatic and asymptomatic
      patients, and features were assessed for association with subsequent therapeutic
      interventions. RESULTS: Of the 91 patients who had radiofrequency EA and
      subsequent ultrasound, 63 patients (69.2%) were symptomatic on evaluation.
      Symptomatic patients were significantly more likely than asymptomatic patients to
      have an endometrial thickness of 3 mm or more, a heterogeneous endometrial
      echotexture, and leiomyomas (P = 0.004, P = 0.008, and P = 0.05, respectively).
      The most frequent finding in all patients was an indistinct endometrial border
      (66/79 [83.5%]). In addition, there was a tendency for patients with leiomyomas
      to have a subsequent intervention (P = 0.07). Although infrequent, all patients
      (7/91) with cornual hematometra or proximal hydrosalpinx had pain. CONCLUSIONS:
      Indistinct endometrial border is a common finding after radiofrequency EA and is
      unrelated to the presence or absence of symptoms. Patients who present with post
      radiofrequency EA symptoms seem to have a few specific ultrasound characteristics
      that differentiate them from asymptomatic patients. The presence of leiomyomas on
      ultrasound is predictive of the need for therapeutic interventions.

PMID- 23149511
TI  - Ultrasound tissue characterization of the normal kidney.
AB  - AIM: Ultrasound tissue characterization (USTC) is a precursor of ultrasound
      virtual histology (USVH), already applied to B-mode images of coronary, carotid,
      and peripheral arteries, as well as venous thrombosis. Elevated echogenicity has
      been described for a rejected transplanted kidney. We analyzed data from healthy
      young adults as reference for further renal USTC. METHODS: Ultrasound kidney
      images of 10 volunteers were analyzed. Pixel brightness in the 0-to-255 range was
      rescaled to zero for black and 200 for fascia brightness before automatic
      classification into 14 ranges, including "blood-like" (0-4), "fat-like" (8-26),
      "hypoechoic muscle-like" (41-60), "hyperechoic muscle-like" (61-76), 4 ranges of
      "fiber-like" (112-196), "calcium-like" (211-255) and intermediary intervals.
      Nomenclature was readapted using nonechoic, hypoechoic I to IV, echoic I to IV,
      hyperechoic I to IV, and saturated echoes to avoid inference to actual kidney
      tissue. Descriptive and comparative statistics were based on percentages of
      pixels in specific brightness ranges. SAMPLE POPULATION: Eight women and 2 men,
      26 +/- 4 years (range, 22-34 years) old, were studied. Kidney length was 10.5 +/-
      0.9 cm (9.0-12.0 cm). Doppler US resistivity index was 0.67 +/- 0.03 (0.62-0.71).
      RESULTS: Original fascia brightness converted to 200 value had a mean +/- SD of
      206 +/- 16 (range, 181-236). Kidney grayscale median averaged 37 +/- 6 (27-48).
      Most pixels were hypoechoic II to IV (8-60), averaging 78% +/- 6% (66%-87%).
      Percentages for fat-like, intermediary fat/muscle-like, and hypoechoic muscle
      like intervals averaged 25%, 28%, and 25%, respectively. CONCLUSIONS: A reference
      database for USTC/USVH of normal young kidneys was created for future comparisons
      with transplanted and abnormal kidneys. Normal renal echoes have low brightness.
      Hyperechoic pixels may represent abnormalities.

PMID- 23149512
TI  - Correlates of depressive symptom severity in problem and pathological gamblers in
      couple relationships.
AB  - Problem and pathological gamblers (PPG) often suffer from depressive symptoms.
      Gambling problems have negative consequences on multiple aspects of gamblers'
      lives, including family and marital relationships. The objectives of the current
      study were to (1) replicate the results of studies that have suggested a stronger
      and more significant relationship between gambling and depression in PPG than in
      non-problem gamblers (NPG) and (2) explore specific correlates of depressive
      symptom severity in PPG in couple relationships. Variables demonstrated to be
      significantly correlated with depressive symptoms in the general population were
      selected. It was hypothesized that gender, age, gambler's mean annual income,
      perceived poverty, employment status, clinical status (i.e., problem or
      pathological gambler versus non-problem gambler), trait anxiety, alcoholism,
      problem-solving skills, and dyadic adjustment would be significant predictors of
      depressive symptoms. Sixty-seven PPG were recruited, primarily from an addiction
      treatment center; 40 NPG were recruited, primarily through the media. Results
      revealed that PPG reported significantly greater depressive symptoms than did
      NPG. Further, elevated trait anxiety and poor dyadic adjustment were demonstrated
      to be significant and specific correlates of depressive symptom severity in PPG.
      These findings contribute to the literature on depressive symptomatology in PPG
      in relationships, and highlight the importance of the influence of the couple
      relationship on PPG. 

PMID- 23149513
TI  - Impaired metacognitive capacities in individuals with problem gambling.
AB  - Impaired insight into behavior may be one of the clinical characteristics of
      pathological gambling. In the present study, we tested whether the capacity to
      evaluate accurately the quality of one's own decisions during a non-gambling task
      was impaired in problem gamblers. Twenty-five problem gamblers and 25 matched
      healthy participants performed an artificial grammar-learning paradigm, in which
      the quality of choice remains uncertain throughout the task. After each trial of
      this task, participants had to indicate how confident they were in the
      grammaticality judgements using a scale ranging from 1 (low confidence) to 7
      (high confidence). Results showed that (i), problem gamblers' performance on the
      grammaticality test was lower than controls'; (ii) there was a significant
      correlation between grammaticality judgments and confidence for control
      participants, which indicates metacognitive insight and the presence of conscious
      knowledge; (iii) this correlation was not significant in problem gamblers, which
      suggests a disconnection between performance and confidence in this group. These
      findings suggest that problem gamblers are impaired in their metacognitive
      abilities on a non-gambling task, which suggests that compulsive gambling is
      associated with poor insight as a general factor. Clinical interventions tailored
      to improve metacognition in gambling could be a fruitful avenue of research in
      order to prevent pathological gambling. 

PMID- 23149514
TI  - Statins inhibit in vitro virulence phenotypes of Pseudomonas aeruginosa.

PMID- 23149515
TI  - Dispersal of Bap-mediated Staphylococcus aureus biofilm by proteinase K.
AB  - The dominant role of biofilm-associated protein (Bap) in Staphylococcus aureus
      biofilm development prompted us to investigate Bap as a potential target for
      proteinase-mediated biofilm dispersion. Biofilm assay in microtitre plates showed
      that proteinase K hampered the early adhesion of cells as well as biofilm
      development. Proteinase K treatment of 24- and 48-h-old biofilms showed enhanced
      dispersion of bap-positive S. aureus biofilm; however, proteinase K did not
      affect the bap-negative S. aureus biofilm. When antibiotics were used in
      combination with proteinase K, significant enhancement in antibiotic action was
      noticed against bap-positive S. aureus biofilm. This study establishes that
      antibiotics in combination with proteinase K can be used for controlling S.
      aureus biofilms in whose development Bap surface protein has a major role. We
      propose that Bap protein could be a potential target for therapeutic control of
      S. aureus infections (for example, bovine mastitis).

PMID- 23149516
TI  - Elaiomycins K and L, new azoxy antibiotics from Streptomyces sp. Tu 6399*.
AB  - Elaiomycins K and L, two new azoxy-type antibiotics, were detected by HPLC-diode
      array screening in the culture filtrate extract of Streptomyces sp. Tu 6399. The
      structures were determined by high-resolution MS and 2-dimensional (1)H and (13)C
      correlated NMR spectroscopy including (15)N-NMR experiments and established these
      compounds as new members of the elaiomycin family. Both metabolites show a weak
      antibacterial activity against Bacillus subtilis and Staphylococcus lentus as
      well as against the phytophathogenic strain Xanthomonas campestris.

PMID- 23149517
TI  - Bis-imidazolinylindoles are active against methicillin-resistant Staphylococcus
      aureus and multidrug-resistant Mycobacterium tuberculosis.

PMID- 23149518
TI  - New method for isolating antibiotic-producing fungi.
AB  - A convenient and efficient method was established for isolating antifungal
      antibiotic-producing fungi from soil samples. In this method, soil samples were
      diluted and directly plated in agar medium by the standard fungi-isolating
      method, and the plates were cultured at 27  degrees C for 2-3 days to permit the
      growth of fungal colonies. Then, the suspension of pathogenic Candida albicans in
      saline (40 MUl, 5-10 * 105 CFU ml-1) was overlaid by spraying on the plates under
      controlled conditions in the safety cabinet. After 1-day incubation, fungal
      colonies showing an antagonistic effect with the inhibition zone against sprayed
      C. albicans were selected. Among 151 isolates, 26 strains were found to reproduce
      anti-C. albicans activity in liquid medium, yielding a higher selection rate
      (17.2%) than that (3.1%) by the traditional method. This new method can be
      applied for isolation of microorganisms (fungi and actinomycetes) that produce
      antibiotics active against pathogenic microorganisms.

PMID- 23149520
TI  - Alzheimer's disease.

PMID- 23149521
TI  - Brain tumors.

PMID- 23149522
TI  - Parkinsonism.

PMID- 23149523
TI  - Seizures and epilepsy in adolescents and adults.

PMID- 23149524
TI  - The price of false beliefs: unrealistic expectations as a contributor to the
      health care crisis.

PMID- 23149525
TI  - Patients' expectations of screening and preventive treatments.
AB  - PURPOSE: An informed decision to accept a health care intervention requires an
      understanding of its likely benefit. This study assessed participants' estimates
      of the benefit, as well as minimum acceptable benefit, of screening for breast
      and bowel cancer and medication to prevent hip fracture and cardiovascular
      disease. METHODS: Three general practitioners sent questionnaires to all
      registered patients aged 50 to 70 years. Patients agreeing to participate in the
      study were asked to estimate the number of events (fractures or deaths) prevented
      in a group of 5,000 patients undergoing each intervention over a period of 10
      years, and to indicate the minimum number of events avoided by the intervention
      that they considered justified its use. The proportions of participants that
      overestimated each intervention's benefit were calculated, and univariate and
      multivariable analyses of predictors of response were performed. RESULTS: The
      participation rate was 36%: 977 patients were invited to participate in the
      study, and 354 returned a completed questionnaire. Participants overestimated the
      degree of benefit conferred by all interventions: 90% of participants
      overestimated the effect of breast cancer screening, 94% overestimated the effect
      of bowel cancer screening, 82% overestimated the effect of hip fracture
      preventive medication, and 69% overestimated the effect of preventive medication
      for cardiovascular disease. Estimates of minimum acceptable benefit were more
      conservative, but other than for cardiovascular disease mortality prevention,
      most respondents indicated a minimum benefit greater than these interventions
      achieve. A lower level of education was associated with higher estimates of
      minimum acceptable benefit for all interventions. CONCLUSION: Patients
      overestimated the risk reduction achieved with 4 examples of screening and
      preventive medications. A lower level of education was associated with higher
      minimum benefit to justify intervention use. This tendency to overestimate
      benefits may affect patients' decisions to use such interventions, and
      practitioners should be aware of this tendency when discussing these
      interventions with patients.

PMID- 23149526
TI  - Projecting US primary care physician workforce needs: 2010-2025.
AB  - PURPOSE: We sought to project the number of primary care physicians required to
      meet US health care utilization needs through 2025 after passage of the
      Affordable Care Act. METHODS: In this projection of workforce needs, we used the
      Medical Expenditure Panel Survey to calculate the use of office-based primary
      care in 2008. We used US Census Bureau projections to account for demographic
      changes and the American Medical Association's Masterfile to calculate the number
      of primary care physicians and determine the number of visits per physician. The
      main outcomes were the projected number of primary care visits through 2025 and
      the number of primary care physicians needed to conduct those visits. RESULTS:
      Driven by population growth and aging, the total number of office visits to
      primary care physicians is projected to increase from 462 million in 2008 to 565
      million in 2025. After incorporating insurance expansion, the United States will
      require nearly 52,000 additional primary care physicians by 2025. Population
      growth will be the largest driver, accounting for 33,000 additional physicians,
      while 10,000 additional physicians will be needed to accommodate population
      aging. Insurance expansion will require more than 8,000 additional physicians, a
      3% increase in the current workforce. CONCLUSIONS: Population growth will be the
      greatest driver of expected increases in primary care utilization. Aging and
      insurance expansion will also contribute to utilization, but to a smaller extent.

PMID- 23149527
TI  - Incidental chest radiographic findings in adult patients with acute cough.
AB  - PURPOSE: Imaging may produce unexpected or incidental findings with consequences
      for patients and ordering of future investigations. Chest radiography in patients
      with acute cough is among the most common reasons for imaging in primary care,
      but data on associated incidental findings are lacking. We set out to describe
      the type and prevalence of incidental chest radiography findings in primary care
      patients with acute cough. METHODS: We report on data from a cross-sectional
      study in 16 European primary care networks on 3,105 patients with acute cough,
      all of whom were undergoing chest radiography as part of a research study workup.
      Apart from assessment for specified signs of pneumonia and acute bronchitis,
      local radiologists were asked to evaluate any additional finding on the
      radiographs. For the 2,823 participants with good-quality chest radiographs,
      these findings were categorized according to clinical relevance based on previous
      research evidence and analyzed for type and prevalence by network, sex, age, and
      smoking status. RESULTS: Incidental findings were reported in 19% of all
      participants, and ranged from 0% to 25% by primary care network, with the network
      being an independent contributor (P <.001). Of all participants 3% had clinically
      relevant incidental findings. Suspected nodules and shadows were reported in
      1.8%. Incidental findings were more common is older participants and smokers (P
      <. 001). CONCLUSIONS: Clinically relevant incidental findings on chest
      radiographs in primary care adult patients with acute cough are uncommon, and
      prevalence varies by setting.

PMID- 23149528
TI  - Promoting safe prescribing in primary care with a contraceptive vital sign: a
      cluster-randomized controlled trial.
AB  - PURPOSE: Routine assessment of women's pregnancy intentions and contraceptive use
      a so-called contraceptive vital sign-may help primary care physicians identify
      patients who need preconception or contraceptive counseling and be of particular
      benefit when teratogenic medications are prescribed. METHODS: We conducted a
      cluster-randomized controlled trial to evaluate the effect of a contraceptive
      vital sign on primary care documentation of contraceptive use and change in
      primary care physicians' provision of family planning services. Academic
      internists in the intervention group (n = 26) were provided with information on
      their female patients' pregnancy intentions and contraceptive use immediately
      before visits; internists in the control group (n = 27) received only standard
      intake information. Data were abstracted from the electronic health record for
      5,371 visits by 2,304 women aged 18 to 50 years. RESULTS: Documentation of
      contraception increased from baseline, from 23% to 57% in the intervention group,
      but remained 28% in the control group, a change of +77.4 (95% confidence interval
      [CI], 70.7 to 84.1) adjusted percentage points in the former vs +3.1 (95% CI, 1.2
      to 5.0) in the latter (P <.001). For visits involving a teratogenic prescription,
      documentation increased from 14% to 48% in the intervention group and decreased
      from 29% to 26% in the control group, a change of +61.5 (95% CI, 35.8 to 87.1)
      adjusted percentage points in the former vs -0.3 (95% CI, -4.3 to 3.6) in the
      latter (P <.001). Provision of new family planning services increased only
      minimally with this intervention, however. When women with documented nonuse of
      contraception were prescribed potential teratogens, only 7% were provided family
      planning services. CONCLUSIONS: A contraceptive vital sign improves documentation
      of contraceptive use; however, ongoing efforts are needed to improve provision of
      preconception and contraceptive services.

PMID- 23149529
TI  - Airway obstruction and bronchodilator responsiveness in adults with acute cough.
AB  - PURPOSE: We sought to determine the prevalence of airway obstruction and
      bronchodilator responsiveness in adults consulting for acute cough in primary
      care. METHODS: Family physicians recruited 3,105 adult patients with acute cough
      (28 days or shorter) attending primary care practices in 12 European countries.
      After exclusion of patients with preexisting physician-diagnosed asthma or
      chronic obstructive pulmonary disease (COPD), we undertook complete case analysis
      of spirometry results (n = 1,947) 28 to 35 days after inclusion. Bronchodilator
      responsiveness was diagnosed if there were recurrent complaints of wheezing,
      cough, or dyspnea and an increase of the forced expiratory volume in 1 second
      (FEV(1)) of 12% or more after bronchodilation. Airway obstruction was diagnosed
      according to 2 thresholds for the (postbronchodilator) ratio of FEV(1) to forced
      vital capacity (FEV(1):FVC): less than 0.7 and less than the lower limit of
      normal. RESULTS: There were 240 participants who showed bronchodilator
      responsiveness (12%), 193 (10%) had a FEV(1)/FVC ratio of less than 0.7, and 126
      (6%) had a ratio of less than the lower limit of normal. Spearman's correlation
      between the 2 definitions of obstruction was 0.71 (P <.001), with discordance
      most pronounced among those younger than 30 years and in older participants.
      CONCLUSIONS: Both bronchodilator responsiveness and persistent airway obstruction
      are common in adults without established asthma or COPD who consult for acute
      cough in primary care, which suggests a high risk of undiagnosed asthma and COPD.
      Different accepted methods to define airway obstruction detected different
      numbers of patients, especially at the extremes of age. As both conditions
      benefit from appropriate and timely interventions, clinicians should be aware and
      responsive to potential underdiagnosis.

PMID- 23149530
TI  - Low primary cesarean rate and high VBAC rate with good outcomes in an Amish
      birthing center.
AB  - PURPOSE: Recent national guidelines encourage a trial of labor after cesarean
      (TOLAC) as a means of increasing vaginal births after cesarean (VBACs) and
      decreasing the high US cesarean birth rate and its consequences (2010 National
      Institute of Health Consensus Statement and American College of Obstetricians and
      Gynecologists revised guideline). A birthing center serving Amish women in
      Southwestern Wisconsin offered an opportunity to look at the effects of local
      culture and practices that support vaginal birth and TOLAC. This study describes
      childbirth and perinatal outcomes during a 17-year period in LaFarge, Wisconsin.
      METHODS: We undertook a retrospective analysis of the records of all women
      admitted to the birth center in labor. Main outcome measures include rates of
      cesarean deliveries, TOLAC and VBAC deliveries, and perinatal outcomes for 927
      deliveries between 1993 and 2010. RESULTS: The cesarean rate was 4% (35 of 927),
      the TOLAC rate was 100%, and the VBAC rate was 95% (88 of 92). There were no
      cases of uterine rupture and no maternal deaths. The neonatal death rate of 5.4
      of 1,000 was comparable to that of Wisconsin (4.6 of 1,000) and the United States
      (4.5 of 1,000). CONCLUSIONS: Both the culture of the population served and a
      number of factors relating to the management of labor at the birthing center have
      affected the rates of cesarean delivery and TOLAC. The results of the LaFarge
      Amish study support a low-technology approach to delivery where good outcomes are
      achieved with low cesarean and high VBAC rates.

PMID- 23149531
TI  - Interventions to improve influenza and pneumococcal vaccination rates among
      community-dwelling adults: a systematic review and meta-analysis.
AB  - PURPOSE: Influenza and pneumococcal vaccination rates remain below national
      targets. We systematically reviewed the effectiveness of quality improvement
      interventions for increasing the rates of influenza and pneumococcal vaccinations
      among community-dwelling adults. METHODS: We included randomized and
      nonrandomized studies with a concurrent control group. We estimated pooled odds
      ratios using random effects models, and used the Downs and Black tool to assess
      the quality of included studies. RESULTS: Most studies involved elderly primary
      care patients. Interventions were associated with improvements in the rates of
      any vaccination (111 comparisons in 77 studies, pooled odds ratio [OR] = 1.61,
      95% CI, 1.49-1.75), and influenza (93 comparisons, 65 studies, OR = 1.46, 95% CI,
      1.35-1.57) and pneumococcal (58 comparisons, 35 studies, OR = 2.01, 95% CI, 1.72
      2.3) vaccinations. Interventions that appeared effective were patient financial
      incentives (influenza only), audit and feedback (influenza only), clinician
      reminders, clinician financial incentives (influenza only), team change, patient
      outreach, delivery site changes (influenza only), clinician education
      (pneumococcus only), and case management (pneumococcus only). Patient outreach
      was more effective if personal contact was involved. Team changes were more
      effective where nurses administered influenza vaccinations independently.
      Heterogeneity in some pooled odds ratios was high, however, and funnel plots
      showed signs of potential publication bias. Study quality varied but was not
      associated with outcomes. CONCLUSIONS: Quality improvement interventions,
      especially those that assign vaccination responsibilities to nonphysician
      personnel or that activate patients through personal contact, can modestly
      improve vaccination rates in community-dwelling adults. To meet national policy
      targets, more-potent interventions should be developed and evaluated.

PMID- 23149532
TI  - Vitamin D supplementation for nonspecific musculoskeletal pain in non-Western
      immigrants: a randomized controlled trial.
AB  - PURPOSE: Many non-Western immigrants report musculoskeletal pains that are hard
      to treat. We studied the effect of high-dose vitamin D(3) on nonspecific
      persistent musculoskeletal complaints in vitamin D-deficient non-Western
      immigrants and assessed correlation of pain patterns with benefit. METHODS: We
      conducted a semi-crossover randomized controlled trial between February 2008 and
      February 2010 in primary care in 84 non-Western immigrants visiting their general
      practitioner for nonspecific musculoskeletal pain. At baseline, patients were
      randomized to placebo or vitamin D (150,000 IU vitamin D(3) orally); at week 6,
      patients in the original vitamin D group were randomized a second time to receive
      vitamin D (again) or to switch to placebo, whereas patients in the original
      placebo group were all switched to vitamin D. The main outcome was self-assessed
      change in pain after the first 6 weeks. RESULTS: Patients in the vitamin D group
      were significantly more likely than their counterparts in the placebo group to
      report pain relief 6 weeks after treatment (34.9% vs 19.5%, P = .04). The former
      were also more likely to report an improved ability to walk stairs (21.0% vs
      8.4%, P = .008). Pain pattern was not correlated with the success of treatment.
      In a nonsignificant trend, patients receiving vitamin D over 12 weeks were more
      likely to have an improvement than patients receiving it over 6 weeks.
      CONCLUSIONS: There is a small positive effect 6 weeks after high-dose vitamin
      D(3) on persistent nonspecific musculoskeletal pain. Future research should focus
      on longer follow-up, higher supplementation doses, and mental health.

PMID- 23149533
TI  - Treatment of ingrown toenail with proximolateral matrix partial excision and
      matrix phenolization.
AB  - PURPOSE: Ingrown toenail is one of the most common nail conditions. Although many
      surgical treatments are described for complicated cases, recurrence of pain and
      postoperative disability are common. We evaluated the long-term efficacy of
      proximolateral matrix partial excision followed by chemical matricectomy with
      phenol. METHODS: We performed 348 proximolateral partial matricectomies and
      phenol ablations in 225 patients with stage 2 or 3 ingrown toenail. Patients were
      examined weekly until full wound healing was achieved and were observed for 24
      months to assess the long-term efficacy of the treatment. RESULTS: Short-term
      results were good. We observed only 1 recurrence during the 24-month follow-up
      period, at 8 months. The success rate was therefore 99.7%. No severe
      complications occurred. Cosmetic results were remarkably good. CONCLUSIONS:
      Proximolateral partial matricectomy with phenol ablation is an excellent surgical
      method for the treatment of ingrown toenails, having low morbidity and a high
      success rate, even in the long term.

PMID- 23149534
TI  - A model for the electronic support of practice-based research networks.
AB  - PURPOSE: The principal goal of the electronic Primary Care Research Network
      (ePCRN) is to enable the development of an electronic infrastructure to support
      clinical research activities in primary care practice-based research networks
      (PBRNs). We describe the model that the ePCRN developed to enhance the growth and
      to expand the reach of PBRN research. METHODS: Use cases and activity diagrams
      were developed from interviews with key informants from 11 PBRNs from the United
      States and United Kingdom. Discrete functions were identified and aggregated into
      logical components. Interaction diagrams were created, and an overall composite
      diagram was constructed describing the proposed software behavior. Software for
      each component was written and aggregated, and the resulting prototype
      application was pilot tested for feasibility. A practical model was then created
      by separating application activities into distinct software packages based on
      existing PBRN business rules, hardware requirements, network requirements, and
      security concerns. RESULTS: We present an information architecture that provides
      for essential interactions, activities, data flows, and structural elements
      necessary for providing support for PBRN translational research activities. The
      model describes research information exchange between investigators and clusters
      of independent data sites supported by a contracted research director. The model
      was designed to support recruitment for clinical trials, collection of aggregated
      anonymous data, and retrieval of identifiable data from previously consented
      patients across hundreds of practices. CONCLUSIONS: The proposed model advances
      our understanding of the fundamental roles and activities of PBRNs and defines
      the information exchange commonly used by PBRNs to successfully engage community
      health care clinicians in translational research activities. By describing the
      network architecture in a language familiar to that used by software developers,
      the model provides an important foundation for the development of electronic
      support for essential PBRN research activities.

PMID- 23149536
TI  - Independent practice authority for nurse practitioners could splinter care,
      undermine patient-centered medical home.

PMID- 23149535
TI  - Reconciling primary care and specialist perspectives on prostate cancer
      screening.
AB  - When specialists propose screening guidelines for primary care clinicians to
      implement, differences in perspectives between the 2 groups can create conflicts.
      Two recent specialty organization guidelines illustrate this issue. The American
      Urological Association guideline panel and National Comprehensive Cancer Network
      recommend that average-risk men first be counseled about the risks and benefits
      of prostate-specific antigen screening for prostate cancer at age 40 rather than
      at the previously recommended age of 50 years. There is no direct evidence,
      however, that this recommendation has any impact on prostate cancer-specific
      mortality. To avoid distracting primary care clinicians from providing services
      with proven benefit and value for patients, professional organizations should
      follow appropriate standards for developing guidelines. Primary care societies
      and health care systems should also be encouraged to evaluate the evidence and
      decide whether implementing the recommendations are feasible and appropriate.

PMID- 23149537
TI  - Knowledge assessment responses in the ABFM self-assessment modules (SAMs).

PMID- 23149538
TI  - At STFM, research is a priority.

PMID- 23149539
TI  - It's not about us: moving the focus to the team and the patient.

PMID- 23149540
TI  - CERA: what? So what? Now what?

PMID- 23149541
TI  - PBRN conference a success.

PMID- 23149543
TI  - piggyBac transposon system modification of primary human T cells.
AB  - The piggyBac transposon system is naturally active, originally derived from the
      cabbage looper moth. This non-viral system is plasmid based, most commonly
      utilizing two plasmids with one expressing the piggyBac transposase enzyme and a
      transposon plasmid harboring the gene(s) of interest between inverted repeat
      elements which are required for gene transfer activity. PiggyBac mediates gene
      transfer through a "cut and paste" mechanism whereby the transposase integrates
      the transposon segment into the genome of the target cell(s) of interest.
      PiggyBac has demonstrated efficient gene delivery activity in a wide variety of
      insect, mammalian, and human cells6 including primary human T cells. Recently, a
      hyperactive piggyBac transposase was generated improving gene transfer
      efficiency. Human T lymphocytes are of clinical interest for adoptive
      immunotherapy of cancer. Of note, the first clinical trial involving transposon
      modification of human T cells using the Sleeping beauty transposon system has
      been approved. We have previously evaluated the utility of piggyBac as a non
      viral methodology for genetic modification of human T cells. We found piggyBac to
      be efficient in genetic modification of human T cells with a reporter gene and a
      non-immunogenic inducible suicide gene. Analysis of genomic integration sites
      revealed a lack of preference for integration into or near known proto-oncogenes.
      We used piggyBac to gene-modify cytotoxic T lymphocytes to carry a chimeric
      antigen receptor directed against the tumor antigen HER2, and found that gene
      modified T cells mediated targeted killing of HER2-positive tumor cells in vitro
      and in vivo in an orthotopic mouse model. We have also used piggyBac to generate
      human T cells resistant to rapamycin, which should be useful in cancer therapies
      where rapamycin is utilized. Herein, we describe a method for using piggyBac to
      genetically modify primary human T cells. This includes isolation of peripheral
      blood mononuclear cells (PBMCs) from human blood followed by culture, gene
      modification, and activation of T cells. For the purpose of this report, T cells
      were modified with a reporter gene (eGFP) for analysis and quantification of gene
      expression by flow cytometry. PiggyBac can be used to modify human T cells with a
      variety of genes of interest. Although we have used piggyBac to direct T cells to
      tumor antigens, we have also used piggyBac to add an inducible safety switch in
      order to eliminate gene modified cells if needed. The large cargo capacity of
      piggyBac has also enabled gene transfer of a large rapamycin resistant mTOR
      molecule (15 kb). Therefore, we present a non-viral methodology for stable gene
      modification of primary human T cells for a wide variety of purposes.

PMID- 23149544
TI  - Novel glucosamine hydrochloride-rectorite nanocomposites with antioxidant and
      anti-ultraviolet activity.
AB  - In this study, an attempt was made to prepare novel D-glucosamine hydrochloride
      rectorite (DGH-REC) nanocomposites with improved antioxidant and anti-ultraviolet
      activity via the solution-intercalation method. The structure and morphology of
      DGH-REC nanocomposites were characterized by XRD, TEM, (13)C CP/MAS NMR, FT-IR,
      XPS and SEM. The results showed that the interlayer distance of REC was enlarged
      after intercalation of DGH; the largest value reached 11.76 nm, and in this case
      exfoliation of the REC layer was observed. Moreover, most strong crystals of DGH
      were greatly disrupted while two other weak crystals of DGH were stronger after
      intercalation of DGH into REC. More importantly, it was found that DGH-REC
      nanocomposites showed pronounced antioxidant activity, in contrast with DGH, and
      the nanocomposites had anti-ultraviolet capacity, which was not observed in DGH.
      Furthermore, the nanocomposites did not show apparent cytotoxicity. Therefore,
      DGH-REC nanocomposites have great potential in health or functional food
      application as compared to DGH.

PMID- 23149545
TI  - Contribution of the AcrAB-TolC efflux pump to high-level fluoroquinolone
      resistance in Escherichia coli isolated from dogs and humans.
AB  - Fluoroquinolone resistance is mainly caused by mutations in quinolone resistance
      determining regions of DNA gyrase and topoisomerase IV in Escherichia coli. The
      AcrAB-TolC efflux pump contributes to resistance against fluoroquinolone and
      other antimicrobials. In this study, we investigated a high-level mechanism of
      fluoroquinolone resistance in E. coli that was isolated from human clinical
      samples and canine fecal samples. E. coli strains with high levels of
      fluoroquinolone resistance have been found to be frequently resistant to
      cephalosporins. Strains with high-level fluoroquinolone resistance exhibited
      lower intracellular enrofloxacin (ENR) concentrations, higher expression of AcrA,
      and a greater reduction in the fluoroquinolone minimum inhibitory concentration
      for treatment with an efflux pump inhibitor. The frequency of strains with
      enhanced ENR resistance selection and the survival rate of E. coli in the
      presence of ENR in vitro were correlated well with AcrA protein expression levels
      in the parental strains. These results suggest that AcrAB-TolC efflux pump over
      expression is related to high-level fluoroquinolone resistance and the selection
      of strains with enhanced fluoroquinolone resistance.

PMID- 23149546
TI  - Escherichia coli isolates from calf diarrhea in Korea and their virulent genetic
      characteristics.
AB  - Escherichia coli strains were isolated from the feces of 130 diarrheic calves at
      different farms locations in Korea. The presence of the virulence genes, such as
      fanC, f41, f17a, eaeA, clpG, afa-8D, sta, stx1 and stx2, in each E. coli isolate
      was examined. Among the 314 isolates, 157 carried one or more of the virulence
      genes tested in this study. The most prevalent virulence gene was clpG (45.9%),
      although f17A (36.9%) and afa-8D (21.7%) were also frequently observed. The sta,
      stx1 and eaeA genes were detected in between approximately 13 and 17% of the
      isolates, and the fanC and fim41a genes were detected to a lesser extent.
      Collectively, our data indicated that diarrhea in calves in these locations can
      be ascribed to various virulence factors, and the pathogenesis may be more
      related to virulence genes such as, clpG, f17A, and afa-8D.

PMID- 23149547
TI  - The defect of Ku70 affects sensitivity to x-ray and radiation-induced caspase
      dependent apoptosis in lung cells.
AB  - The DNA repair protein Ku70 is a key player in chemoresistance to anticancer
      agents (e.g., etoposide) or radioresistance. The responses of different organs to
      radiation vary widely and likely depend on the cell population in the organs.
      Previously, we established and characterized Ku70-deficient murine lung
      epithelial (Ku70 -/- MLE) cells and found that these cells are more sensitive
      than Ku70 +/- MLE cells (control cells) to X-irradiation, as determined by
      clonogenic survival assay; however, the mechanism underlying this sensitivity
      remains unclear. In this study, we examined the mechanism by which X-irradiation
      triggers the death of Ku70 -/- MLE cells. Our results showed that Ku70 -/- MLE
      cells were more sensitive to radiation-induced apoptosis than control cells,
      although X-irradiation activated caspase-3 and caspase-7, and cleaved PARP in
      both cell lines. We also examined the expression level of phosphorylated H2AX
      (gammaH2AX), which is a marker of DSB, and observed the phosphorylation of H2AX
      and the elimination of gammaH2AX in both cell lines after X-irradiation. The
      elimination in Ku70 -/- MLE cells was slower than that in control cells,
      suggesting that DSB repair activity in the Ku70 -/- MLE cells is lower than that
      in control cells. These findings suggest that Ku70 might play a key role in the
      inhibition of apoptosis through the DSB repair pathway in lung epithelial cells.
      Our findings also suggest that these cell lines might be useful for the study of
      Ku70 functions and the Ku70-dependent DSB repair pathway in lung epithelial
      cells.

PMID- 23149548
TI  - Metal-only Lewis pairs featuring unsupported Pt->M (M = Zn or Cd) dative bonds.
AB  - Reactions of [Pt(PCy(3))(2)] (Cy = cyclohexyl) with group 12 metal dihalides have
      afforded the novel metal only Lewis pair (MOLP) complexes, [(Cy(3)P)(2)Pt->MX(2)]
      (M = Zn or Cd, X = Br or I), or the oxidative addition product, trans
      [(Cy(3)P)(2)(I)PtHgI]. The zinc complex represents the first MOLP to contain an
      unsupported Pt->Zn linkage.

PMID- 23149549
TI  - Characterization of cultured epithelial cells using a novel technique not
      requiring enzymatic digestion for subculturing.
AB  - Our laboratory had developed a methodology to expand epithelial cells in culture
      by growing keratinocyte monolayers, under large volumes of medium that produces
      large numbers of keratinocytes that leave the monolayer and move into suspension.
      The cells have been defined as epithelial Pop Up Keratinocytes or ePUKs cells and
      appear to be highly suitable for clinical applications. In this publication we
      extend the characterization of the cells with a detailed analysis of the
      capabilities of the monolayer of a single culture flask to produce, over time,
      ePUK cells. The cells were characterized using standard epithelial markers for
      proliferation and differentiation. Analysis of morphology of the monolayer formed
      and total number of cells produced is presented for a variety of human epithelial
      cell strains. These keratinocytes provide an additional controlled human cell
      system for investigation of the mechanisms regulating epithelia cell growth and
      differentiation and since they are produced in large numbers, they are highly
      suitable for use in epithelial cell banking.

PMID- 23149550
TI  - Microarrays of gold nanoparticle clusters fabricated by Stop&Go convective self
      assembly for SERS-based sensor chips.
AB  - SERS substrates fabricated from chemically synthesized nanoparticles (NPs) offer
      a distinct advantage of localizing and enhancing the electromagnetic fields by
      facile tuning of NP size, shape and interparticle distances. In this report, two
      dimensional arrays of micrometre-sized clusters of gold nanoparticles protected
      by (i) sodium citrate and (ii) tris(2,4-dimethyl-5-sulfonatophenyl)phosphine
      (TDSP) ligands were directly assembled from colloidal suspensions onto flat, non
      patterned substrates by discontinuous ('Stop&Go') convective self-assembly. The
      micrometric spacing between the NP clusters makes it easy to address them
      individually by confocal Raman microscopy. The packing of the gold NPs within
      these clusters with interparticle spacings of the order of nanometres leads to an
      optical response dominated by coupled surface plasmon resonances, and favours a
      strong enhancement of electromagnetic fields useful for surface enhanced Raman
      scattering (SERS). These NP clusters make very uniform SERS substrates, with
      reproducible SERS responses from cluster to cluster. The potential of these NP
      clusters for optical biosensing is demonstrated by the SERS detection of a
      biologically relevant molecule, cytosine, adsorbed onto the NP clusters. The
      presented results are promising for designing an original class of nanoparticle
      based SERS microarrays. The new paradigm of convective self-assembly could be
      exploited generally for the patterning of various other types of colloidal micro-
      and nano-objects, such as semiconducting NPs, magnetic NPs, bacteria or proteins.

PMID- 23149551
TI  - The modulation rate transfer function of a harbour porpoise (Phocoena phocoena).
AB  - During echolocation, toothed whales produce ultrasonic clicks at extremely rapid
      rates and listen for the returning echoes. The auditory brainstem response (ABR)
      duration was evaluated in terms of latency between single peaks: 5.5 ms (from
      peak I to VII), 3.4 ms (I-VI), and 1.4 ms (II-IV). In comparison to the killer
      whale and the bottlenose dolphin, the ABR of the harbour porpoise has shorter
      intervals between the peaks and consequently a shorter ABR duration. This
      indicates that the ABR duration and peak latencies are possibly related to the
      relative size of the auditory structures of the central nervous system and thus
      to the animal's size. The ABR to a sinusoidal amplitude modulated stimulus at 125
      kHz (sensitivity threshold 63 dB re 1 MUPa rms) was evaluated to determine the
      modulation rate transfer function of a harbour porpoise. The ABR showed distinct
      envelope following responses up to a modulation rate of 1,900 Hz. The
      corresponding calculated equivalent rectangular duration of 263 MUs indicates a
      good temporal resolution in the harbour porpoise auditory system similar to the
      one for the bottlenose dolphin. The results explain how the harbour porpoise can
      follow clicks and echoes during echolocation with very short inter click
      intervals.

PMID- 23149552
TI  - Long-term clinical and radiological results of endovascular internal trapping in
      vertebral artery dissection.
AB  - INTRODUCTION: Previous reports have suggested that endovascular parent artery
      occlusion is an effective and safe procedure for the treatment of vertebral
      artery dissection (VAD). However, the results of long-term outcomes are still
      unclear. This study reviewed the clinical and imaging outcomes of patients with
      VAD treated by endovascular internal trapping. METHODS: A total of 73 patients
      were treated for VAD by endovascular internal trapping between March 1998 and
      March 2011. Patients were regularly followed up by magnetic resonance imaging,
      magnetic resonance angiography, and clinical examinations. Clinical outcomes were
      evaluated using the modified Rankin Scale. RESULTS: Forty-five patients had
      ruptured VADs, and 28 had unruptured VADs. Clinical follow-up of at least 6
      months data was obtained for 61 patients (83.6 %). The follow-up period ranged
      from 6 to 145 months (mean +/- SD, 55.6 +/- 8.9 months). Two patients with
      ruptured VADs had recurrence (2.74 %). Cranial nerve paresis (CNP) was observed
      in six patients (8.21 %), spinal cord infarction in two patients (2.74 %), and a
      perforating artery ischemia was diagnosed in seven patients (9.59 %); all
      patients with CNP and five of the patients with partial Wallenberg syndrome
      experienced only temporary symptoms; two of the patients with partial Wallenberg
      syndrome had permanent neurological deficits. Despite their symptoms, most
      patients were in good general condition, as shown by their clinical scores.
      CONCLUSIONS: The results of this study have proven that endovascular internal
      trapping is a stable and durable treatment for closure of VADs. Recanalization is
      rather rare and occurred only in ruptured cases, both within 3 months after
      initial treatment without rupture. CNPs were observed in 8.21 %, perforating
      ischemia in 9.59 %, and spinal cord infarction in 2.74 %. The former two are
      temporary, while the last can be a factor that affects the modified Rankin Scale.
      Patients rated their quality of life as good, as corroborated by their
      posttreatment clinical score. Endovascular internal trapping for VAD is a therapy
      with a satisfactory long-term outcome.

PMID- 23149553
TI  - Early brain injury alters the blood-brain barrier phenotype in parallel with beta
      amyloid and cognitive changes in adulthood.
AB  - Clinical studies suggest that traumatic brain injury (TBI) hastens cognitive
      decline and development of neuropathology resembling brain aging. Blood-brain
      barrier (BBB) disruption following TBI may contribute to the aging process by
      deregulating substance exchange between the brain and blood. We evaluated the
      effect of juvenile TBI (jTBI) on these processes by examining long-term
      alterations of BBB proteins, beta-amyloid (Abeta) neuropathology, and cognitive
      changes. A controlled cortical impact was delivered to the parietal cortex of
      male rats at postnatal day 17, with behavioral studies and brain tissue
      evaluation at 60 days post-injury (dpi). Immunoglobulin G extravasation was
      unchanged, and jTBI animals had higher levels of tight-junction protein claudin 5
      versus shams, suggesting the absence of BBB disruption. However, decreased P
      glycoprotein (P-gp) on cortical blood vessels indicates modifications of BBB
      properties. In parallel, we observed higher levels of endogenous rodent Abeta in
      several brain regions of the jTBI group versus shams. In addition at 60 dpi, jTBI
      animals displayed systematic search strategies rather than relying on spatial
      memory during the water maze. Together, these alterations to the BBB phenotype
      after jTBI may contribute to the accumulation of toxic products, which in turn
      may induce cognitive differences and ultimately accelerate brain aging.

PMID- 23149554
TI  - Assessment of leptomeningeal collaterals using dynamic CT angiography in patients
      with acute ischemic stroke.
AB  - Whole-brain dynamic time-resolved computed tomography angiography (CTA) is a
      technique developed on the new 320-detector row CT scanner capable of generating
      time-resolved cerebral angiograms from skull base to vertex. Unlike a
      conventional cerebral angiogram, this technique visualizes pial arterial filling
      in all vascular territories, thereby providing additional hemodynamic
      information. Ours was a retrospective study of consecutive patients with ischemic
      stroke and M1 middle cerebral artery +/- intracranial internal carotid artery
      occlusions presenting to our center from June 2010 and undergoing dynamic time
      resolved CTA and perfusion CT within 6 hours of symptom onset. Leptomeningeal
      collateral status was assessed by determining relative prominence of pial
      arteries in the ischemic region, rate and extent of retrograde flow, and various
      topographical patterns of pial arterial filling. Twenty-five patients were
      included in the study. We demonstrate the existence of the following novel
      properties of leptomeningeal collaterals in humans: (a) posterior (posterior
      cerebral artery (PCA)-MCA) dominant collateralization, (b) intra-territorial
      'within MCA region' leptomeningeal collaterals, and (c) significant variability
      in size, extent, and retrograde filling time in pial arteries. We also describe a
      simple and reliable collateral grading template that, for the first time on
      dynamic CTA, incorporates back-filling time as well as size and extent of
      collateral filling.

PMID- 23149555
TI  - Ischemic-LTP in striatal spiny neurons of both direct and indirect pathway
      requires the activation of D1-like receptors and NO/soluble guanylate
      cyclase/cGMP transmission.
AB  - Striatal medium-sized spiny neurons (MSNs) are highly vulnerable to ischemia. A
      brief ischemic insult, produced by oxygen and glucose deprivation (OGD), can
      induce ischemic long-term potentiation (i-LTP) of corticostriatal excitatory
      postsynaptic response. Since nitric oxide (NO) is involved in the pathophysiology
      of brain ischemia and the dopamine D1/D5-receptors (D1-like-R) are expressed in
      striatal NOS-positive interneurons, we hypothesized a relation between NOS
      positive interneurons and striatal i-LTP, involving D1R activation and NO
      production. We investigated the mechanisms involved in i-LTP induced by OGD in
      corticostriatal slices and found that the D1-like-R antagonist SCH-23390
      prevented i-LTP in all recorded MSNs. Immunofluorescence analysis confirmed the
      induction of i-LTP in both substance P-positive, (putative D1R-expressing) and
      adenosine A2A-receptor-positive (putative D2R-expressing) MSNs. Furthermore, i
      LTP was dependent on a NOS/cGMP pathway since pharmacological blockade of NOS,
      guanylate-cyclase, or PKG prevented i-LTP. However, these compounds failed to
      prevent i-LTP in the presence of a NO donor or cGMP analog, respectively.
      Interestingly, the D1-like-R antagonism failed to prevent i-LTP when
      intracellular cGMP was pharmacologically increased. We propose that NO, produced
      by striatal NOS-positive interneurons via the stimulation of D1-like-R located on
      these cells, is critical for i-LTP induction in the entire population of MSNs
      involving a cGMP-dependent pathway.

PMID- 23149556
TI  - Glibenclamide enhances neurogenesis and improves long-term functional recovery
      after transient focal cerebral ischemia.
AB  - Glibenclamide is neuroprotective against cerebral ischemia in rats. We studied
      whether glibenclamide enhances long-term brain repair and improves behavioral
      recovery after stroke. Adult male Wistar rats were subjected to transient middle
      cerebral artery occlusion (MCAO) for 90 minutes. A low dose of glibenclamide
      (total 0.6 MUg) was administered intravenously 6, 12, and 24 hours after
      reperfusion. We assessed behavioral outcome during a 30-day follow-up and animals
      were perfused for histological evaluation. In vitro specific binding of
      glibenclamide to microglia increased after pro-inflammatory stimuli. In vivo
      glibenclamide was associated with increased migration of doublecortin-positive
      cells in the striatum toward the ischemic lesion 72 hours after MCAO, and
      reactive microglia expressed sulfonylurea receptor 1 (SUR1) and Kir6.2 in the
      medial striatum. One month after MCAO, glibenclamide was also associated with
      increased number of NeuN-positive and 5-bromo-2-deoxyuridine-positive neurons in
      the cortex and hippocampus, and enhanced angiogenesis in the hippocampus.
      Consequently, glibenclamide-treated MCAO rats showed improved performance in the
      limb-placing test on postoperative days 22 to 29, and in the cylinder and water
      maze test on postoperative day 29. Therefore, acute blockade of SUR1 by
      glibenclamide enhanced long-term brain repair in MCAO rats, which was associated
      with improved behavioral outcome.

PMID- 23149557
TI  - Intravenous HOE-642 reduces brain edema and Na uptake in the rat permanent middle
      cerebral artery occlusion model of stroke: evidence for participation of the
      blood-brain barrier Na/H exchanger.
AB  - Cerebral edema forms in the early hours of ischemic stroke by processes involving
      increased transport of Na and Cl from blood into brain across an intact blood
      brain barrier (BBB). Our previous studies provided evidence that the BBB Na-K-Cl
      cotransporter is stimulated by the ischemic factors hypoxia, aglycemia, and
      arginine vasopressin (AVP), and that inhibition of the cotransporter by
      intravenous bumetanide greatly reduces edema and infarct in rats subjected to
      permanent middle cerebral artery occlusion (pMCAO). More recently, we showed that
      BBB Na/H exchanger activity is also stimulated by hypoxia, aglycemia, and AVP.
      The present study was conducted to further investigate the possibility that a BBB
      Na/H exchanger also participates in edema formation during ischemic stroke.
      Sprague-Dawley rats were subjected to pMCAO and then brain edema and Na content
      assessed by magnetic resonance imaging diffusion-weighed imaging and magnetic
      resonance spectroscopy Na spectroscopy, respectively, for up to 210 minutes. We
      found that intravenous administration of the specific Na/H exchange inhibitor HOE
      642 significantly decreased brain Na uptake and reduced cerebral edema, brain
      swelling, and infarct volume. These findings support the hypothesis that edema
      formation and brain Na uptake during the early hours of cerebral ischemia involve
      BBB Na/H exchanger activity as well as Na-K-Cl cotransporter activity.

PMID- 23149558
TI  - Critical closing pressure determined with a model of cerebrovascular impedance.
AB  - Critical closing pressure (CCP) is the arterial blood pressure (ABP) at which
      brain vessels collapse and cerebral blood flow (CBF) ceases. Using the concept of
      impedance to CBF, CCP can be expressed with brain-monitoring parameters: cerebral
      perfusion pressure (CPP), ABP, blood flow velocity (FV), and heart rate. The
      novel multiparameter method (CCPm) was compared with traditional transcranial
      Doppler (TCD) calculations of CCP (CCP1). Digital recordings of ABP, intracranial
      pressure (ICP), and TCD-based FV from previously published studies of 29 New
      Zealand White rabbits were reanalyzed. Overall, CCP1 and CCPm showed correlation
      across wide ranges of ABP, ICP, and PaCO2 (R=0.93, P<0.001). Three physiological
      perturbations were studied: increase in ICP (n=29) causing both CCP1 and CCPm to
      increase (P<0.001 for both); reduction of ABP (n=10) resulting in decrease of
      CCP1 (P=0.006) and CCPm (P=0.002); and controlled increase of PaCO2 (n=8) to
      hypercapnic levels, which decreased CCP1 and CCPm, albeit insignificantly
      (P=0.123 and P=0.306 respectively), caused by a spontaneous significant increase
      in ABP (P=0.025). Multiparameter mathematical model of critical closing pressure
      explains the relationship of CCP on brain-monitoring variables, allowing the
      estimation of CCP during cases such as hypercapnia-induced hyperemia, where
      traditional calculations, like CCP1, often reach negative non-physiological
      values.

PMID- 23149559
TI  - Higher coated-platelet levels are associated with stroke recurrence following
      nonlacunar brain infarction.
AB  - Coated-platelets are procoagulant platelets observed upon dual-agonist
      stimulation with collagen and thrombin. Coated-platelet levels are elevated in
      patients with nonlacunar (large-vessel) ischemic stroke and decreased in patients
      with spontaneous intracerebral hemorrhage as compared with controls. The purpose
      of this study was to investigate a possible relationship between coated-platelet
      levels and stroke recurrence in patients with nonlacunar ischemic stroke. We
      assayed coated-platelet levels in 190 consecutive patients with nonlacunar stroke
      who were followed for up to 12 months; 20 subjects experienced recurrent stroke.
      Subjects were categorized into tertiles of coated-platelet levels. The
      distributions of time-to-recurrent stroke were estimated for each tertile using
      cumulative incidence curves and compared statistically using a log-rank test. The
      cumulative incidence of recurrent stroke at 12 months differed among the coated
      platelet tertiles: 2% for the first tertile (lowest coated-platelet levels), 18%
      for the second tertile, and 17% for the third tertile (overall log-rank test,
      P=0.019). These data suggest that higher levels of coated-platelets, measured
      shortly after a nonlacunar stroke, are associated with an increased incidence of
      stroke recurrence. This observation offers an additional tool for identifying
      patients at highest risk for stroke recurrence following a nonlacunar (large
      vessel) infarct.

PMID- 23149560
TI  - In vivo imaging of dopaminergic neurotransmission after transient focal ischemia
      in rats.
AB  - The precise biologic mechanisms involved in functional recovery processes in
      response to stroke such as dopaminergic neurotransmission are still largely
      unknown. For this purpose, we performed in parallel in vivo magnetic resonance
      imaging and positron emission tomography (PET) with [(18)F]fluorodeoxyglucose
      ([(18)F]FDG) and [(11)C]raclopride at 1, 3, 7, 14, 21, and 28 days after middle
      cerebral artery occlusion in rats. In the ischemic territory, PET [(18)F]FDG
      showed a initial decrease in cerebral metabolism followed by a time-dependent
      recovery to quasi-normal values at day 14 after ischemia. The PET with
      [(11)C]raclopride, a ligand for dopamine D(2) receptor, showed a sustained
      binding during the first week after ischemia that declined dramatically from day
      14 to day 28. Interestingly, a slight increase in [(11)C]raclopride binding was
      observed at days 1 to 3 followed by the uppermost binding at day 7 in the
      contralateral territory. Likewise, in vitro autoradiography using
      [(3)H]raclopride confirmed these in vivo results. Finally, the neurologic test
      showed major neurologic impairment at day 1 followed by a recovery of the
      cerebral function at day 28 after cerebral ischemia. Taken together, these
      results might suggest that dopamine D(2) receptor changes in the contralateral
      hemisphere could have a key role in functional recovery after cerebral ischemia.

PMID- 23149562
TI  - Pulse wave analysis of aortic pressure:  diastole should also be considered.
AB  - BACKGROUND: The systolic augmentation index (sAix), calculated from the central
      aortic pulse wave (reconstructed from the noninvasive recording of the radial
      pulse with applanation tonometry), is widely used as a simple index of central
      arterial stiffness, but has the disadvantage of also being influenced by the
      timing of the reflected with respect to the forward pressure wave, as shown by
      its inverse dependence on heart rate (HR). During diastole, the central aortic
      pulse also contains reflected waves, but their relationship to arterial stiffness
      and HR has not been studied. METHODS: In 48 men and 45 women, all healthy, with
      ages ranging from 19 to 70 years, we measured pulse wave velocity (PWV, patients
      supine), a standard evaluator of arterial stiffness, and carried out radial
      applanation tonometry (patients sitting and supine). The impact of reflected
      waves on the diastolic part of the aortic pressure waveform was quantified in the
      form of a diastolic augmentation index (dAix). RESULTS: Across ages, sexes, and
      body position, there was an inverse relationship between the sAix and the dAix.
      When PWV and HR were added as covariates to a prediction model including age, sex
      and body position as main factors, the sAix was directly related to PWV (P <
      0.0001) and inversely to HR (P < 0.0001). With the same analysis, the dAix was
      inversely related to PWV (P < 0.0001) and independent of HR (P = 0.52).
      CONCLUSION: The dAix has the same degree of linkage to arterial stiffness as the
      more conventional sAix, while being immune to the confounding effect of HR. The
      quantification of diastolic aortic pressure augmentation by reflected waves could
      be a useful adjunct to pulse wave analysis.

PMID- 23149561
TI  - Hyperforin attenuates brain damage induced by transient middle cerebral artery
      occlusion (MCAO) in rats via inhibition of TRPC6 channels degradation.
AB  - Hyperforin, a lipophilic constituent of medicinal herb St John's wort, has been
      identified as the main active ingredient of St John's wort extract for
      antidepressant action by experimental and clinical studies. Hyperforin is
      currently known to activate transient receptor potential canonical (subtype) 6
      (TRPC6) channel, increase the phosphorylated CREB (p-CREB), and has N-methyl-D
      aspartate receptor-antagonistic effect that convert potential neuroprotective
      effects in vitro. However, the protective effects of hyperforin on ischemic
      stroke in vivo remain controversial and its neuroprotective mechanisms are still
      unclear. This study was designed to examine the effects of
      intracerebroventricular (i.c.v.) injection of hyperforin on transient focal
      cerebral ischemia in rats. Hyperforin, when applied immediately after middle
      cerebral artery occlusion (MCAO) onset, significantly reduced infarct volumes and
      apoptotic cells, and also increased neurologic scores at 24 hours after
      reperfusion accompanied by elevated TRPC6 and p-CREB activity and decreased
      SBDP145 activity. When MEK or CaMKIV activity was specifically inhibited, the
      neuroprotective effect of hyperforin was attenuated, and we observed a correlated
      decrease in CREB activity. In conclusion, our results clearly showed that i.c.v.
      injection of hyperforin immediately after MCAO onset blocked calpain-mediated
      TRPC6 channels degradation, and then to stimulate the Ras/MEK/ERK and CaMKIV
      pathways that converge on CREB activation, contributed to neuroprotection.

PMID- 23149563
TI  - Heredity and cardiometabolic risk: naturally occurring polymorphisms in the human
      neuropeptide Y(2) receptor promoter disrupt multiple transcriptional response
      motifs.
AB  - OBJECTIVES: The neuropeptide Y(2) G-protein-coupled receptor (NPY2R) relays
      signals from PYY or neuropeptide Y toward satiety and control of body mass.
      Targeted ablation of the NPY2R locus in mice yields obesity, and studies of NPY2R
      promoter genetic variation in more than 10,000 human participants indicate its
      involvement in control of obesity and BMI. Here we searched for genetic variation
      across the human NPY2R locus and probed its functional effects, especially in the
      proximal promoter. METHODS AND RESULTS: Twin pair studies indicated substantial
      heritability for multiple cardiometabolic traits, including BMI, SBP, DBP, and
      PYY, an endogenous agonist at NPY2R. Systematic polymorphism discovery by
      resequencing across NPY2R uncovered 21 genetic variants, 10 of which were common
      [minor allele frequency (MAF) >5%], creating one to two linkage disequilibrium
      blocks in multiple biogeographic ancestries. In vivo, NPY2R haplotypes were
      associated with both BMI (P = 3.75E-04) and PYY (P = 4.01E-06). Computational
      approaches revealed that proximal promoter variants G-1606A, C-599T, and A-224G
      disrupt predicted IRF1 (A>G), FOXI1 (T>C), and SNAI1 (A>G) response elements. In
      neuroendocrine cells transfected with NPY2R promoter/luciferase reporter
      plasmids, all three variants and their resulting haplotypes influenced
      transcription (G-1606A, P < 2.97E-06; C-599T, P < 1.17E-06; A-224G, P < 2.04E
      06), and transcription was differentially augmented or impaired by coexpression
      of either the cognate full-length transcription factors or their specific siRNAs
      at each site. Endogenous expression of transcripts for NPY2R, IRF1, and SNAI1 was
      documented in neuroendocrine cells, and the NPY2R mRNA was differentially
      expressed in two neuroendocrine tissues (adrenal gland, brainstem) of a rodent
      model of hypertension and the metabolic syndrome, the spontaneously hypertensive
      rat. CONCLUSION: We conclude that common genetic variation in the proximal NPY2R
      promoter influences transcription factor binding so as to alter gene expression
      in neuroendocrine cells, and consequently cardiometabolic traits in humans. These
      results unveil a novel control point, whereby cis-acting genetic variation
      contributes to control of complex cardiometabolic traits, and point to new
      transcriptional strategies for intervention into neuropeptide actions and their
      cardiometabolic consequences.

PMID- 23149564
TI  - Antioxidant ability and mechanism of rhizoma Atractylodes macrocephala.
AB  - Rhizoma Atractylodes macrocephala (AM) has been used in Traditional Chinese
      Medicine (TCM) for about 2,000 years. In the study, we firstly determined the
      antioxidant levels of five AM extracts by *OH-scavenging, *O2--scavenging, Fe2+
      chelating, Cu2+-chelating, DPPH.-scavenging, and ABTS+.-scavenging assays. After
      measurement of the chemical contents in five AM extracts, we quantitatively
      analyzed the correlations between antioxidant levels and chemical contents. It
      was observed that total phenolics and total flavonoids had significant positive
      correlations with antioxidant levels (R = 0.685 and 0.479, respectively). In
      contrast, total sugars and total saponins presented lower correlations with
      antioxidant levels (R=-0.272 and 0.244, respectively). It means that antioxidant
      activity of AM should be attributed to total phenolics (including phenolic acids
      and flavonoids), and not total sugars and total saponins. Further analysis
      indicated that phenolic acids exhibited higher R values with radical-scavenging
      assays (R=0.32-1.00), while flavonoids showed higher R values with metal
      chelating assays (R=0.86 and 0.90). In conclusion, AM exerts its antioxidant
      effect through metal-chelating, and radical-scavenging which is via donating
      hydrogen atom and donating electron. Its metal-chelating may result from
      flavonoids, while its radical-scavenging can be attributed to phenolic acids,
      especially caffeic acid, ferulic acid, and protocatechuic acid.

PMID- 23149565
TI  - Wild Argentinian Amaryllidaceae, a new renewable source of the
      acetylcholinesterase inhibitor galanthamine and other alkaloids.
AB  - The Amaryllidaceae family is well known for its pharmacologically active
      alkaloids. An important approach to treat Alzheimer's disease involves the
      inhibition of the enzyme acetylcholinesterase (AChE). Galanthamine, an
      Amaryllidaceae alkaloid, is an effective, selective, reversible, and competitive
      AchE inhibitor. This work was aimed at studying the alkaloid composition of four
      wild Argentinian Amarillydaceae species for the first time, as well as analyzing
      their inhibitory activity on acetylcholinesterase. Alkaloid content was
      characterized by means of GC-MS analysis. Chloroform basic extracts from
      Habranthus jamesonii, Phycella herbertiana, Rhodophiala mendocina and
      Zephyranthes filifolia collected in the Argentinian Andean region all contained
      galanthamine, and showed a strong AChE inhibitory activity (IC50 between 1.2 and
      2 ug/mL). To our knowledge, no previous reports on alkaloid profiles and AChEIs
      activity of wild Argentinian Amarillydaceae species have been publisihed. The
      demand for renewable sources of industrial products like galanthamine and the
      need to protect plant biodiversity creates an opportunity for Argentinian farmers
      to produce such crops.

PMID- 23149566
TI  - CAFM investigations of filamentary conduction in Cu2O ReRAM devices fabricated
      using stencil lithography technique.
AB  - With the objective of understanding the role of size and current level of
      filamentary regions on the resistive switching parameters, detailed conductive
      atomic force microscope investigations of resistive memory cells having different
      dimensions have been carried out in this study. Cu-Cu(2)O-Ti memory cells having
      dimensions of 150, 50 and 25 MUm have been fabricated on the same substrate using
      a stencil lithography technique. The dependence of resistive switching parameters
      on the device dimensions can be directly related to the average size, current
      level of the filaments and difference in these parameters between the low
      resistance state (LRS) and high resistance state (HRS). It is observed that the
      large increase in the ratio of current in the two states in cells having lower
      dimensions is mainly due to the smaller number of conducting regions in the HRS,
      indicating efficient switching from the LRS to the HRS at lower dimensions.

PMID- 23149567
TI  - Instabilities and diffusion in a hydrodynamic model of a fluid membrane coupled
      to a thin active fluid layer.
AB  - We construct a coarse-grained effective two-dimensional (2d hydrodynamic theory
      as a theoretical model for a coupled system of a fluid membrane and a thin layer
      of a polar active fluid in its ordered state that is anchored to the membrane. We
      show that such a system is prone to generic instabilities through the interplay
      of nonequilibrium drive, polar order and membrane fluctuation. We use our model
      equations to calculate diffusion coefficients of an inclusion in the membrane and
      show that their values depend strongly on the system size, in contrast to their
      equilibrium values. Our work extends the work of S. Sankararaman and S. Ramaswamy
      (Phys. Rev. Lett., 102, 118107 (2009)) to a coupled system of a fluid membrane
      and an ordered active fluid layer. Our model is broadly inspired by and should be
      useful as a starting point for theoretical descriptions of the coupled dynamics
      of a cell membrane and a cortical actin layer anchored to it.

PMID- 23149568
TI  - Perceptions, barriers, and suggestions for creation of a tobacco and health
      website among American Indian/Alaska Native college students.
AB  - Information concerning American Indian/Alaska Native (AI/AN) Internet use and
      health information needs is dearth. Our research team explored Internet use among
      AI/AN college students to determine Internet use in relation to health
      information seeking behaviors. We used a tobacco site example for participants to
      describe what they desired in a health site designed specifically for AI/AN.
      Using a community-based participatory research approach, we conducted 14 focus
      groups with AI/AN college students (N = 108), to better understand their
      perceptions of and attitudes toward Internet use and health information needs.
      Daily Internet use was reported across strata yet health topics investigated
      differed among groups. Participants in all strata desired a health website that
      was easy to navigate and interactive. Respectful representation of Native culture
      was a concern, yet no consensus was reached for a multi-tribal audience.
      Participants felt a website should use caution with cultural depictions due to
      the possible misinterpretation. Overall, participants agreed that recreational
      and traditional tobacco use should be differentiated and the variation of
      traditional use among tribes acknowledged. Data concerning Internet use for
      health information among AI/AN college students are needed to establish baseline
      indicators to effectively address disparities.

PMID- 23149569
TI  - Willingness to access peer-delivered HIV testing and counseling among people who
      inject drugs in Bangkok, Thailand.
AB  - Peer-based models for human immunodeficiency virus (HIV) testing have been
      implemented to increase access to testing in various settings. However, little is
      known about the acceptability of peer-delivered testing and counseling among
      people who inject drugs (IDU). During July and October 2011, data derived from
      the Mitsampan Community Research Project were used to construct three
      multivariate logistic regression models identifying factors associated with
      willingness to receive peer-delivered pre-test counseling, rapid HIV testing, and
      post-test counseling. Among a total of 348 IDU, 44, 38, and 36 % were willing to
      receive peer-delivered pre-test counseling, rapid HIV testing, and post-test
      counseling, respectively. In multivariate analyses, factors associated with
      willingness to access peer-delivered pre-test counseling included: male gender
      (adjusted odds ratio (AOR) = 0.48), higher than secondary education (AOR = 1.91),
      and binge drug use (AOR = 2.29) (all p < 0.05). Factors associated with
      willingness to access peer-delivered rapid HIV testing included: higher than
      secondary education (AOR = 2.06), binge drug use (AOR = 2.23), incarceration (AOR
      = 2.68), avoiding HIV testing (AOR = 0.24), and having been to the Mitsampan Harm
      Reduction Center (AOR = 1.63) (all p < 0.05). Lastly, binge drug use (AOR =
      2.40), incarceration (AOR = 1.94), and avoiding HIV testing (AOR = 0.23) (all p <
      0.05) were significantly associated with willingness to access peer-delivered
      post-test counseling. We found that a substantial proportion of Thai IDU were
      willing to receive peer-delivered HIV testing and counseling. These findings
      highlight the potential of peer-delivered testing to complement existing HIV
      testing programs that serve IDU.

PMID- 23149570
TI  - Iterative optimization of DNA duplexes for crystallization of SeqA-DNA complexes.
AB  - Escherichia coli SeqA is a negative regulator of DNA replication that prevents
      premature reinitiation events by sequestering hemimethylated GATC clusters within
      the origin of replication. Beyond the origin, SeqA is found at the replication
      forks, where it organizes newly replicated DNA into higher ordered structures.
      SeqA associates only weakly with single GATC sequences, but it forms high
      affinity complexes with DNA duplexes containing multiple GATC sites. The minimal
      functional and structural unit of SeqA is a dimer, thereby explaining the
      requirement of at least two GATC sequences to form a high-affinity complex with
      hemimethylated DNA. Additionally, the SeqA architecture, with the oligomerization
      and DNA-binding domains separated by a flexible linker, allows binding to GATC
      repeats separated by up to three helical turns. Therefore, understanding the
      function of SeqA at a molecular level requires the structural analysis of SeqA
      bound to multiple GATC sequences. In protein-DNA crystallization, DNA can have
      none to an exceptional effect on the packing interactions depending on the
      relative sizes and architecture of the protein and the DNA. If the protein is
      larger than the DNA or footprints most of the DNA, the crystal packing is
      primarily mediated by protein-protein interactions. Conversely, when the protein
      is the same size or smaller than the DNA or it only covers a fraction of the DNA,
      DNA-DNA and DNA-protein interactions dominate crystal packing. Therefore,
      crystallization of protein-DNA complexes requires the systematic screening of DNA
      length and DNA ends (blunt or overhang). In this report, we describe how to
      design, optimize, purify and crystallize hemimethylated DNA duplexes containing
      tandem GATC repeats in complex with a dimeric variant of SeqA (SeqADelta(41-59)
      A25R) to obtain crystals suitable for structure determination.

PMID- 23149571
TI  - Socio-demographic inequalities in stage of cancer diagnosis: evidence from
      patients with female breast, lung, colon, rectal, prostate, renal, bladder,
      melanoma, ovarian and endometrial cancer.
AB  - BACKGROUND: Understanding socio-demographic inequalities in stage at diagnosis
      can inform priorities for cancer control. PATIENTS AND METHODS: We analysed data
      on the stage at diagnosis of East of England patients diagnosed with any of 10
      common cancers, 2006-2010. Stage information was available on 88 657 of 98 942
      tumours (89.6%). RESULTS: Substantial socio-demographic inequalities in advanced
      stage at diagnosis (i.e. stage III/IV) existed for seven cancers, but their
      magnitude and direction varied greatly by cancer: advanced stage at diagnosis was
      more likely for older patients with melanoma but less likely for older patients
      with lung cancer [odds ratios for 75-79 versus 65-69 1.60 (1.38-1.86) and 0.83
      (0.77-0.89), respectively]. Deprived patients were more likely to be diagnosed in
      advanced stage for melanoma, prostate, endometrial and (female) breast cancer:
      odds ratios (most versus least deprived quintile) from 2.24 (1.66-3.03) for
      melanoma to 1.31 (1.15-1.49) for breast cancer. In England, elimination of socio
      demographic inequalities in stage at diagnosis could decrease the number of
      patients with cancer diagnosed in advanced stage by ~5600 annually. CONCLUSIONS:
      There are substantial socio-demographic inequalities in stage at diagnosis for
      most cancers. Earlier detection interventions and policies can be targeted on
      patients at higher risk of advanced stage diagnosis.

PMID- 23149572
TI  - Fabrication of different morphologies of ZnO superstructures in presence of
      synthesized ethylammonium nitrate (EAN) ionic liquid: synthesis, characterization
      and analysis.
AB  - ZnO particles were synthesized by hydrothermal route at 95  degrees C, with
      different ethylammonium nitrate (EAN) : water volume ratio (0.01 to 1) in
      reaction media. Morphology of ZnO particles changed from initial cylindrical to
      intermediate spindle and finally to spherical with increasing concentration of
      EAN in reaction media whereas pH of aliquots remained within range of 7-7.5.
      Aggregates of EAN bind to Zn(2+) enriched both terminal planes as well as to
      Zn(2+) and O(2-) enriched side planes of basis units which finally resulted to
      formation of spherical ZnO superstructures. Favorable H-bond and electrostatic
      interaction helped to bind EAN aggregates with surfaces of ZnO crystals. It was
      found that the spherical ZnO superstructures showed novel photoluminescent
      property and enhanced photocatalytic activity compared to that of the
      commercially available ZnO.

PMID- 23149573
TI  - The presence of sinusoidal CD163(+) macrophages in lymph nodes is associated with
      favorable nodal status in patients with breast cancer.
AB  - As macrophages are some of the first cells to encounter metastatic tumor cells in
      sentinel lymph nodes (SLN) and natural killer (NK) cells are critical to the
      cytotoxicity of abnormal cells, we sought to determine if these cell populations
      were altered in the presence of nodal metastasis. We used immunohistochemistry to
      assess the SLN of 47 patients with breast cancer (36 with nodal metastasis and 11
      without nodal metastasis) and 10 control lymph nodes. We assessed metastatic
      areas and nonmetastatic areas separately for CD163, a marker of macrophages, and
      ANK-1, a marker for precursors of activated NK cells. Positively stained cells
      were manually counted in multiple high-power fields and averaged. Groups were
      compared with the Kruskal-Wallis test. Spearman rank order test was used for
      correlations. There was a lower frequency of CD163(+) macrophages in the SLN of
      patients with breast cancer (median, 11.0 %; range, 4.1-20.4 %) than controls
      (median, 16.5 %; range, 8.9-19.6 %; p = 0.002). There were no differences in the
      expression of ANK between patients with cancer (median, 1.4 %; range, 0.23-6.3 %)
      and controls (median, 1.5 %; range, 0.60-5.4 %; p = 0.5). In patients with nodal
      metastasis, the accumulation of CD163(+) cells in the sinuses correlated
      negatively with CD8(+) tumor-infiltrating lymphocytes (r (2) = 0.23; p = 0.001).
      These results suggest that the reduction of CD163(+) macrophages in the sinuses
      of the SLN is associated with nodal metastasis and may have a role in regional
      immunity.

PMID- 23149574
TI  - Association of modified cytosines and the methylated DNA-binding protein MeCP2
      with distinctive structural domains of lampbrush chromatin.
AB  - We have investigated the association of DNA methylation and proteins interpreting
      methylation state with the distinctive closed and open chromatin structural
      domains that are directly observable in the lampbrush chromosomes (LBCs) of
      amphibian oocytes. To establish the distribution in LBCs of MeCP2, one of the key
      proteins binding 5-methylcytosine-modified DNA (5mC), we expressed HA-tagged
      MeCP2 constructs in Xenopus laevis oocytes. Full-length MeCP2 was predominantly
      targeted to the closed, transcriptionally inactive chromomere domains in a
      pattern proportional to chromomeric DNA density and consistent with a global role
      in determining chromatin state. A minor fraction of HA-MeCP2 was also found to
      associate with a distinctive structural domain, namely a short region at the
      bases of some of the extended lateral loops. Expression in oocytes of deleted
      constructs and of point mutants derived from Rett syndrome patients demonstrated
      that the association of MeCP2 with LBCs was determined by its 5mC-binding domain.
      We also examined more directly the distribution of 5mC by immunostaining Xenopus
      and axolotl LBCs and confirmed the pattern suggested by MeCP2 targeting of
      intense staining of the chromomeres and of some loop bases. In addition, we found
      in the longer loops of axolotl LBCs that short interstitial regions could also be
      clearly stained for 5mC. These 5mC regions corresponded precisely to unusual
      segments of active transcription units from which RNA polymerase II (pol II) and
      nascent transcripts were simultaneously absent. We also examined by
      immunostaining the distribution in lampbrush chromatin of the oxidized 5mC
      derivative, 5-hydroxymethylcytosine (5hmC). Although in general, the pattern
      resembled that obtained for 5mC, one antibody against 5hmC produced intense
      staining of restricted chromosomal foci. These foci corresponded to a third type
      of lampbrush chromatin domain, the transcriptionally active but less extended
      structures formed by clusters of genes transcribed by pol III. This raises the
      possibility that 5hmC may play a role in establishing the distinctive patterns of
      gene repression and activation that characterize specific pol III-transcribed
      gene families in amphibian genomes.

PMID- 23149575
TI  - Precocious detection on amphibian oocyte lampbrush chromosomes of subtle changes
      in the cellular localisation of the Ro52 protein induced by in vitro culture.
AB  - Subterminal lampbrush loops of one of the 12 bivalents of the oocyte karyotype of
      Pleurodeles waltl (Amphibian, Urodele) underwent prominent morphological changes
      upon in vitro culture. These loops exhibited a fine ribonucleoprotein (RNP)
      granular matrix, which evolved during culture into huge structures that we have
      named 'chaussons' (slippers). This phenomenon involved progressive accumulation
      of proteins in the RNP matrix without protein neosynthesis. One of these
      proteins, which translocated into the nucleus during the culture, was identified
      as a homolog of the human Ro52 E3 ubiquitin ligase. RNA polymerase III was also
      found to accumulate on the same loops. These results suggest that the subterminal
      loops of bivalent XII act as a storage site for the components of a nuclear
      machinery involved in the quality control of RNA synthesis and maturation in
      response to cellular stress. They also emphasise the considerable value of the
      lampbrush chromosome system for a direct visualisation of modifications in gene
      expression and open the question of a nuclear accumulation of Ro52 in human or
      animal oocytes cultured in vitro for assisted reproductive technologies (ART).

PMID- 23149576
TI  - Class-IA phosphoinositide 3-kinase p110beta Triggers GPCR-induced superoxide
      production in p110gamma-deficient murine neutrophils.
AB  - Studies with knockout mice have indicated that the only isoform of
      phosphoinositide 3-kinase (PI3K) functioning in the oxidative burst of mouse
      neutrophils in response to heterotrimeric guanine nucleotide-binding protein
      coupled receptor (GPCR) agonists is a class-IB PI3K, p110gamma. In the present
      study, we observed that the cells from p110gamma(-/-) mice gain a response to N
      formyl-Met-Leu-Phe (fMLP) after priming with cytochalasin E. Even the unprimed
      cells, which show no response to fMLP, produce a significant amount of
      superoxide, when an effective agonist of the mouse-type fMLP receptors, Trp-Lys
      Tyr-Met-Val-D-Met, is used to stimulate the cells. These results suggested that
      the class-IA isoforms (p110alpha, p110beta, and p110delta) of PI3K are sufficient
      to trigger and maintain superoxide production. Examination of the effects of
      isoform-specific inhibitors suggested that the p110beta isoform is the primary
      PI3K triggering the response to GPCR agonists when p110gamma is absent.

PMID- 23149577
TI  - Synergistic effects of galantamine and memantine in attenuating scopolamine
      induced amnesia in mice.
AB  - We investigated a possible drug efficacy enhancement obtained by combining
      inactive doses of galantamine and memantine in the scopolamine-induced amnesia
      model in mice. We evaluated the effects of the two drugs, either alone or in
      combination, using the spontaneous alternation and object recognition tasks. In
      both tests, combination of low doses of galantamine (0.1 mg/kg, s.c.) and
      memantine (0.5 mg/kg, i.p.), which were sub-active per se, rescued the memory
      impairment induced by scopolamine (1 mg/kg, i.p.). The results suggest that
      combinations of galantamine and memantine might provide a more effective
      treatment of memory impairments in cognitive disorders than either drug used
      alone.

PMID- 23149578
TI  - Nicotine- and tar-free cigarette smoke extract induces cell injury via
      intracellular Ca2+-dependent subtype-specific protein kinase C activation.
AB  - Nicotine- and tar-free cigarette smoke extract (CSE) is reported to induce cell
      damage via activation of protein kinase C (PKC) and NADPH oxidase (NOX) in rat C6
      glioma cells. Here we determined PKC isozyme(s) activated by CSE and their
      activation mechanism. In C6 glioma cells, mRNAs for PKCalpha, PKCdelta,
      PKCepsilon, and PKCiota were expressed. CSE triggered translocation of PKCalpha
      and PKCepsilon to plasma membrane. CSE-induced cell damage and PKC translocation
      were inhibited by chelating intracellular Ca(2+) but not extracellular Ca(2+).
      These results suggest that CSE induces cell damage through intracellular Ca(2+)
      dependent activation of PKCalpha and PKCepsilon and subsequent NOX activation.

PMID- 23149579
TI  - The growth and enhanced catalytic performance of Au@Pd core-shell nanodendrites.
AB  - Au@Pd core-shell nanodendrites were synthesized by reducing H(2)PdCl(4) with
      ascorbic acid onto the surface of Au polyhedra at room temperature. The Au@Pd
      core-shell nanodendrites consisting of a Au core and nanoporous Pd shell,
      exhibited plasmonic properties and higher catalytic activity in comparison with
      Au@Pd core-shell nanocubes.

PMID- 23149580
TI  - Evaluation of rK-39 strip test using urine for diagnosis of visceral
      leishmaniasis in an endemic region of India.
AB  - The definitive diagnosis of visceral leishmaniasis (VL) requires invasive
      procedures for demonstration of parasites in tissue smear or culture. These
      procedures need expertise and laboratory supports and cannot be performed in the
      field. The aim of the present study was to evaluate the existing rK-39
      immunochromatographic nitrocellulose strips test (ICT) with some modification in
      human urine for diagnosis of VL. The test was performed on both sera and urine
      samples on the same 786 subjects (365 confirmed VL and 421 control subjects). The
      sensitivity of the rK-39 ICT in serum was 100%, whereas the specificity was
      93.8%, 100%, and 96.2% in healthy controls from endemic, non-endemic, and other
      infectious diseases, respectively. However, in urine samples, the test showed
      96.1% sensitivity and 100% specificity. Considering sensitivity and feasibility
      of the test in the field, rK-39 ICT using urine samples can be an alternative to
      conventional invasive VL diagnosis.

PMID- 23149581
TI  - Dengue virus type 2 modulates endothelial barrier function through CD73.
AB  - Dengue hemorrhagic fever is characterized by a unique vascular leakage syndrome.
      The mechanisms of endothelial barrier dysfunction in dengue hemorrhagic fever are
      not well understood. We examined the modulation of endothelial barrier function
      in dengue virus type 2 (DENV2) infections using primary human umbilical vein
      endothelial cells. We demonstrated that the increase in endothelial barrier
      function within 72 hours after DENV2 infection is mediated by type I interferon
      dependent CD73 up-regulation. After 72 hours, DENV2 slowed the recovery of
      endothelial barrier function in response to tumor necrosis factor-alpha or
      vascular endothelial growth factor. This phenomenon was likely caused by type I
      interferon receptor signaling inhibition and lower CD73 levels in DENV2-infected
      endothelial cells. Our findings suggest that during DENV2 infection, endothelial
      barrier homeostasis is maintained by a balance between pro-inflammatory and pro
      angiogenic cytokines, and type I interferon-dependent CD73 expression and
      activity.

PMID- 23149582
TI  - Controlled human malaria infections by intradermal injection of cryopreserved
      Plasmodium falciparum sporozoites.
AB  - Controlled human malaria infection with sporozoites is a standardized and
      powerful tool for evaluation of malaria vaccine and drug efficacy but so far only
      applied by exposure to bites of Plasmodium falciparum (Pf)-infected mosquitoes.
      We assessed in an open label Phase 1 trial, infection after intradermal injection
      of respectively 2,500, 10,000, or 25,000 aseptic, purified, vialed, cryopreserved
      Pf sporozoites (PfSPZ) in three groups (N = 6/group) of healthy Dutch volunteers.
      Infection was safe and parasitemia developed in 15 of 18 volunteers (84%), 5 of 6
      volunteers in each group. There were no differences between groups in time until
      parasitemia by microscopy or quantitative polymerase chain reaction, parasite
      kinetics, clinical symptoms, or laboratory values. This is the first successful
      infection by needle and syringe with PfSPZ manufactured in compliance with
      regulatory standards. After further optimization, the use of such PfSPZ may
      facilitate and accelerate clinical development of novel malaria drugs and
      vaccines.

PMID- 23149583
TI  - Decreasing intestinal parasites in recent Northern California refugees.
AB  - Beginning in 2005, the Centers for Disease Control and Prevention (CDC) expanded
      the overseas presumptive treatment of intestinal parasites with albendazole to
      include refugees from the Middle East. We surveyed the prevalence of helminths
      and protozoa in recent Middle Eastern refugees (2008-2010) in comparison with
      refugees from other geographical regions and from a previous survey (2001-2004)
      in Santa Clara County, California. Based on stool microscopy, helminth infections
      decreased, particularly in Middle Eastern refugees (0.1% versus 2.3% 2001-2004, P
      = 0.01). Among all refugees, Giardia intestinalis was the most common protozoan
      found. Protozoa infections also decreased somewhat in Middle Eastern refugees
      (7.2%, 2008-2010 versus 12.9%, 2001-2004, P = 0.08). Serology for Strongyloides
      stercoralis and Schistosoma spp. identified more infected individuals than stool
      exams. Helminth infections are increasingly rare in refugees to Northern
      California. Routine screening stool microscopy may be unnecessary in all
      refugees.

PMID- 23149584
TI  - Cross-sectional study of Leptospira seroprevalence in humans, rats, mice, and
      dogs in a main tropical sea-port city.
AB  - Samples were collected from 128 symptomatic humans, 83 dogs, 49 mice, and 20 rats
      (Rattus rattus: 16; Rattus norvegicus: 4) in neighborhoods where human
      leptospirosis have been reported within the principal sea-port city of Colombia.
      Seroprevalences were assessed against 19 pathogenic, 1 intermediate pathogenic,
      and 1 saprophytic Leptospira serogroups. Pathogenic Leptospira were confirmed
      using conventional Leptospira-specific polymerase chain-reaction and pulsed-field
      gel electrophoresis analysis was used for serovar identification. Seroprevalences
      of 20.4%, 12.5%, 25.0%, 22.9%, and 12.4% were obtained against one to seven
      different serogroups in mice, R. rattus, R. norvegicus, dogs, and humans,
      respectively. The DNA was confirmed to be from pathogenic Leptospira by detecting
      the lipL32 gene in 12.5%, 3.7%, and 0.03% of the R. rattus, dog, and human
      samples, respectively. The first genetically typed Colombian isolate was obtained
      from a rat and identified as Leptospira interrogans serovar
      Icterohaemorrhagiae/Copenhageni.

PMID- 23149585
TI  - Pre-travel health care of immigrants returning home to visit friends and
      relatives.
AB  - Immigrants returning home to visit friends and relatives (VFR travelers) are at
      higher risk of travel-associated illness than other international travelers. We
      evaluated 3,707 VFR and 17,507 non-VFR travelers seen for pre-travel consultation
      in Global TravEpiNet during 2009-2011; all were traveling to resource-poor
      destinations. VFR travelers more commonly visited urban destinations than non-VFR
      travelers (42% versus 30%, P < 0.0001); 54% of VFR travelers were female, and 18%
      of VFR travelers were under 6 years old. VFR travelers sought health advice
      closer to their departure than non-VFR travelers (median days before departure
      was 17 versus 26, P < 0.0001). In multivariable analysis, being a VFR traveler
      was an independent predictor of declining a recommended vaccine. Missed
      opportunities for vaccination could be addressed by improving the timing of pre
      travel health care and increasing the acceptance of vaccines. Making pre-travel
      health care available in primary care settings may be one step to this goal.

PMID- 23149587
TI  - Adaptive segmentation of vertebral bodies from sagittal MR images based on local
      spatial information and Gaussian weighted chi-square distance.
AB  - We present a novel method for the automatic segmentation of the vertebral bodies
      from 2D sagittal magnetic resonance (MR) images of the spine. First, a new
      affinity matrix is constructed by incorporating neighboring information, which
      local intensity is considered to depict the image and overcome the noise
      effectively. Second, the Gaussian kernel function is to weight chi-square
      distance based on the neighboring information, which the vital spatial structure
      of the image is introduced to improve the accuracy of the segmentation task.
      Third, an adaptive local scaling parameter is utilized to facilitate the image
      segmentation and avoid the optimal configuration of controlling parameter
      manually. The encouraging results on the spinal MR images demonstrate the
      advantage of the proposed method over other methods in terms of both efficiency
      and robustness.

PMID- 23149586
TI  - West Nile virus ecology in a tropical ecosystem in Guatemala.
AB  - West Nile virus ecology has yet to be rigorously investigated in the Caribbean
      Basin. We identified a transmission focus in Puerto Barrios, Guatemala, and
      established systematic monitoring of avian abundance and infection,
      seroconversions in domestic poultry, and viral infections in mosquitoes. West
      Nile virus transmission was detected annually between May and October from 2005
      to 2008. High temperature and low rainfall enhanced the probability of chicken
      seroconversions, which occurred in both urban and rural sites. West Nile virus
      was isolated from Culex quinquefasciatus and to a lesser extent, from Culex
      mollis/Culex inflictus, but not from the most abundant Culex mosquito, Culex
      nigripalpus. A calculation that combined avian abundance, seroprevalence, and
      vertebrate reservoir competence suggested that great-tailed grackle (Quiscalus
      mexicanus) is the major amplifying host in this ecosystem. West Nile virus
      transmission reached moderate levels in sentinel chickens during 2007, but less
      than that observed during outbreaks of human disease attributed to West Nile
      virus in the United States.

PMID- 23149588
TI  - Stent salvage using the Enterprise stent for procedure-related complication
      during coil embolization of ruptured intracranial aneurysms.
AB  - BACKGROUND: Despite accumulated experience and improved understanding of the
      tools, endovascular treatment of intracranial aneurysms continues to have risks
      linked to the technique itself, and induces procedure-related complications. The
      purpose of this study was to report our series of stent salvage using the
      Enterprise stent for procedure-related complication during coil embolization in
      patients with ruptured intracranial aneurysms. METHODS: Parent artery thrombosis,
      parent artery dissection, and coil protrusion were considered to be the procedure
      related complications. There were 18 consecutive cases (3 unruptured and 15
      ruptured aneurysms) with procedure-related complications rescued by the
      Enterprise stent from December 2008 to December 2011. Follow-up angiography was
      performed in 14 of the 15 patients with ruptured aneurysms between 6 and 30
      months (mean 14.6 months) after the procedure. RESULTS: The procedure-related
      complications were parent artery dissection (n = 1), parent artery thrombosis (n
      = 4), and coil protrusion (n = 10). There was no complication related to
      delivering or deploying of the Enterprise stent. Initial radiographic results
      showed 8 cases of complete occlusion and 7 cases of neck remnant. There was no
      change in the angiographic results during the follow-up periods. CONCLUSIONS:
      Facing with procedure-related complications during coil embolization of ruptured
      intracranial aneurysms, the closed-cell designed Enterprise stent might be a
      useful option for the salvage technique by restoring blood flow and minimizing
      thromboembolic events.

PMID- 23149589
TI  - Vestibular schwannoma presenting with psychosis.

PMID- 23149590
TI  - Endoscopic treatment of convexity arachnoid cysts.
AB  - OBJECTIVE: The aim of this study was to investigate the endoscopic treatment of
      cerebral hemisphere convexity arachnoid cyst. METHODS: Eight cases of hemisphere
      convexity arachnoid cyst treated with cyst-ventricular or cisternal endoscopic
      approach in September 2007 to March 2011 were retrospectively recruited. The
      clinical symptoms, radiological findings, surgical indications, surgical
      approach, complications, and follow-up studies were analyzed. RESULTS: All
      patients showed convexity arachnoid cysts adjacent to the ventricles or
      cisternal. After treatment, all patients showed decrease in size of the cysts
      (100 %), with preoperative symptoms disappeared in six patients and improved in
      two cases. In one case, postoperative subdural effusion was found without
      symptoms reported. CONCLUSION: Endoscopic surgery is ideal for treatment of
      arachnoid cysts adjacent to the ventricles or cisternal.

PMID- 23149591
TI  - Endoscopic third ventriculocisternostomy in hydrocephalic children under 2 years
      of age: appropriate or not? A single-center retrospective cohort study.
AB  - PURPOSE: Treating hydrocephalus can be difficult in children under the age of 2
      years because a high amount of uncertainty exists as to which treatment to
      perform. In this retrospective cohort study, we analyzed children under the age
      of 2 years with hydrocephalus undergoing an endoscopic third
      ventriculocisternostomy (ETV) with respect to ETV outcome. METHODS: In 59
      consecutive patients under the age of 2 years, an ETV was performed between 1999
      and 2010 at the Erasmus MC, Sophia Children's Hospital. Demographics, etiology of
      hydrocephalus, and radiological data were extracted retrospectively from the
      patients' medical records and operative reports and related to outcome. ETV
      Success Score (ETVSS) was used to retrospectively calculate the probability of
      success related to the actual outcome. RESULTS: In this series, 42.4 % of
      patients had a successful ETV. The only statistically significant finding
      concerned age. The failed ETV patients appeared to be younger (0.52 +/- 0.60 vs.
      0.86 +/- 0.56 year, p = 0.005), and when using a cutoff age of 6 months only,
      five out of 32 infants had a successful ETV (p = 0.002). Of the children with an
      arachnoid cyst, 57.1 % were treated successfully with an ETV. Of the five
      patients with a high probability of ETV success, four (80 %) were indeed
      successfully treated with ETV (p = 0.049). CONCLUSIONS: Our data confirm the
      overall ineffectiveness of an ETV in children under the age of 6 months.
      Nevertheless, using the ETVSS is recommended to aid in the decision-making
      process even in patients under the age of 6 months.

PMID- 23149592
TI  - [Daptomycin for the treatment of gram-positive infections after cardiac surgery].
AB  - BACKGROUND AND METHOD: Surgical infection remains a main cause of death after
      heart surgery, despite advances in pharmacological therapy. Daptomycin is a
      cyclic lipopeptide antibiotic, useful in gram-positive organisms resistant to
      standard treatment, including vancomycin. The aim of this study was to describe
      the use of daptomycin regarding efficacy, efficiency and safety in patients with
      gram-positive infections after heart surgery using a retrospective analysis on 49
      adult patients. CONCLUSION: Daptomycin shows excellent in vitro and in vivo
      activity against gram-positive organisms, such as Enterococcus faecalis,
      Enterococcus faecium, Staphylococcus aureus, especially MRSA. Daptomycin is also
      effective against increasing vancomycin-resistant or vancomycin-intermediate S.
      aureus.

PMID- 23149593
TI  - Preparation and antibacterial properties of laser-generated silver-anatase
      nanocomposite film against Escherichia coli and Staphylococcus aureus.
AB  - Anatase-based titanium dioxide (TiO(2)) naturally possesses a well recognized
      antibacterial effect under ultraviolet excitation. However, anatase modified with
      silver nanoparticles (Ag NPs) exhibits even stronger antibacterial action in
      natural daylight. The purpose of our present research is to evaluate the
      photocatalytic antibacterial effects of laser-generated silver-anatase
      nanocomposite film against Escherichia coli (E. coli) and Staphylococcus aureus
      (S. aureus). A sol-gel TiO(2) precursor was spin-coated on a clean glass slide
      and silver ions were self-adsorbed from aqueous solution. A pulsed beam of KrF
      excimer laser (248 nm, 13 ns) was traversed over the amorphous film, leading to
      the crystallization of the anatase and formation of cubic as well as hexagonal Ag
      NPs. A scanning transmission electron microscope analysis revealed a 30-40 nm
      anatase crystallite size, whereas an average size of 9.6 nm was obtained from Ag
      NPs. The photo-absorption of plain anatase was red-shifted to 516 nm with the
      addition of Ag NPs after the laser treatment. Moreover, no colonies of E. coli
      and S. aureus cells were observed to survive after 60 min of contact with the
      laser-modified silver-anatase films in the dark and in daylight conditions.

PMID- 23149594
TI  - Diastolic spontaneous calcium release from the sarcoplasmic reticulum increases
      beat-to-beat variability of repolarization in canine ventricular myocytes after
      beta-adrenergic stimulation.
AB  - RATIONALE: Spontaneous Ca(2+) release (SCR) from the sarcoplasmic reticulum can
      cause delayed afterdepolarizations and triggered activity, contributing to
      arrhythmogenesis during beta-adrenergic stimulation. Excessive beat-to-beat
      variability of repolarization duration (BVR) is a proarrhythmic marker. Previous
      research has shown that BVR is increased during intense beta-adrenergic
      stimulation, leading to SCR. OBJECTIVE: We aimed to determine ionic mechanisms
      controlling BVR under these conditions. METHODS AND RESULTS: Membrane potentials
      and cell shortening or Ca(2+) transients were recorded from isolated canine left
      ventricular myocytes in the presence of isoproterenol. Action-potential (AP)
      durations after delayed afterdepolarizations were significantly prolonged.
      Addition of slowly activating delayed rectifier K(+) current (I(Ks)) blockade led
      to further AP prolongation after SCR, and this strongly correlated with
      exaggerated BVR. Suppressing SCR via inhibition of ryanodine receptors,
      Ca(2+)/calmodulin-dependent protein kinase II inhibition, or by using Mg(2+) or
      flecainide eliminated delayed afterdepolarizations and decreased BVR independent
      of effects on AP duration. Computational analyses and voltage-clamp experiments
      measuring L-type Ca(2+) current (I(CaL)) with and without previous SCR indicated
      that I(CaL) was increased during Ca(2+)-induced Ca(2+) release after SCR, and
      this contributes to AP prolongation. Prolongation of QT, T(peak)-T(end)
      intervals, and left ventricular monophasic AP duration of beats after
      aftercontractions occurred before torsades de pointes in an in vivo dog model of
      drug-induced long-QT1 syndrome. CONCLUSIONS: SCR contributes to increased BVR by
      interspersed prolongation of AP duration, which is exacerbated during I(Ks)
      blockade. Attenuation of Ca(2+)-induced Ca(2+) release by SCR underlies AP
      prolongation via increased I(CaL.) These data provide novel insights into
      arrhythmogenic mechanisms during beta-adrenergic stimulation besides triggered
      activity and illustrate the importance of I(Ks) function in preventing excessive
      BVR.

PMID- 23149596
TI  - Molecular evolution of the genomic RNA of Apple stem grooving capillovirus.
AB  - The complete genome of the German isolate AC of Apple stem grooving virus (ASGV)
      was sequenced. It encodes two overlapping open reading frames (ORFs), similarly
      to previously described ASGV isolates. Two regions of high variability were
      detected between the ASGV isolates, variable region 1 (V1, from amino acids (aa)
      532 to 570), and variable region 2 (V2, from aa 1,583 to 1,868). The phylogenetic
      analysis of the V1 and V2 regions suggested that the ASGV diversity was
      structured by host plant species rather than geographical origin. The dN/dS ratio
      between nonsynonymous and synonymous nucleotide substitution rates varied greatly
      along the ASGV genome. Most of ORF1 showed predominant negative selection except
      for the two regions V1 and V2. V1 showed an elevated dN and an average dS when
      compared to the ORF1 background but no significant positive selection was
      detected. The V2 region of ORF1 showed an elevated dN and a low dS when compared
      to the ORF1 background with an average dN/dS ~ 3.0 indicative of positive
      selection. However, the V2 area includes overlapping ORFs, making the dN/dS
      estimate biased. Joint estimates of the selection intensity in the different ORFs
      by a recent method indicated that this region of ORF1 was in fact evolving close
      to neutrality. This was convergent with previous results showing that
      introduction of stop codons in this region of ORF1 did not impair plant
      infection. These data suggest that the elimination of a stop codon caused the
      overprinting of a novel coding region over the ancestral ORF.

PMID- 23149597
TI  - Bioluminescent bacterial imaging in vivo.
AB  - This video describes the use of whole body bioluminesce imaging (BLI) for the
      study of bacterial trafficking in live mice, with an emphasis on the use of
      bacteria in gene and cell therapy for cancer. Bacteria present an attractive
      class of vector for cancer therapy, possessing a natural ability to grow
      preferentially within tumors following systemic administration. Bacteria
      engineered to express the lux gene cassette permit BLI detection of the bacteria
      and concurrently tumor sites. The location and levels of bacteria within tumors
      over time can be readily examined, visualized in two or three dimensions. The
      method is applicable to a wide range of bacterial species and tumor xenograft
      types. This article describes the protocol for analysis of bioluminescent
      bacteria within subcutaneous tumor bearing mice. Visualization of commensal
      bacteria in the Gastrointestinal tract (GIT) by BLI is also described. This
      powerful, and cheap, real-time imaging strategy represents an ideal method for
      the study of bacteria in vivo in the context of cancer research, in particular
      gene therapy, and infectious disease. This video outlines the procedure for
      studying lux-tagged E. coli in live mice, demonstrating the spatial and temporal
      readout achievable utilizing BLI with the IVIS system.

PMID- 23149595
TI  - Effects of rare and common blood pressure gene variants on essential
      hypertension: results from the Family Blood Pressure Program, CLUE, and
      Atherosclerosis Risk in Communities studies.
AB  - RATIONALE: Hypertension affects ~30% of adults in industrialized countries and is
      the major risk factor for cardiovascular disease. OBJECTIVE: We sought to study
      the genetic effect of coding and conserved noncoding variants in syndromic
      hypertension genes on systolic blood pressure (BP) and diastolic BP to assess
      their overall impact on essential hypertension. METHODS AND RESULTS: We
      resequenced 11 genes (AGT, CYP11B1, CYP17A1, HSD11B2, NR3C1, NR3C2, SCNN1A,
      SCNN1B, SCNN1G, WNK1, and WNK4) in 560 European American (EA) and African
      American ancestry GenNet participants with extreme systolic BP. We investigated
      genetic associations of 2535 variants with BP in 19997 EAs and in 6069 African
      Americans in 3 types of analyses. First, we studied the combined effects of all
      variants in GenNet. Second, we studied 1000 Genomes imputed polymorphic variants
      in 9747 EA and 3207 African American Atherosclerosis Risk in Communities
      subjects. Finally, we genotyped 37 missense and common noncoding variants in 6591
      EAs and in 6521 individuals (3659 EA/2862 African American) from the CLUE and
      Family Blood Pressure Program studies, respectively. None of the variants
      individually reached significant false-discovery rates <=0.05 for systolic BP and
      diastolic BP. However, on pooling all coding and noncoding variants, we
      identified at least 5 loci (AGT, CYP11B1, NR3C2, SCNN1G, and WNK1) with higher
      association at evolutionary conserved sites. CONCLUSIONS: Both rare and common
      variants at these genes affect BP in the general population with modest effects
      sizes (<0.05 standard deviation units), and much larger sample sizes are required
      to assess the impact of individual genes. Collectively, conserved noncoding
      variants affect BP to a greater extent than missense mutations.

PMID- 23149598
TI  - Interstitial cystitis patients' use and rating of complementary and alternative
      medicine therapies.
AB  - INTRODUCTION AND HYPOTHESIS: The purpose of this study was to describe the use of
      complementary and alternative medicine (CAM) therapies among interstitial
      cystitis (IC) patients, patients' perception of CAM therapies' effectiveness, and
      the association of time since diagnosis with perceived effectiveness of these
      therapies. METHODS: In April 2009, the Interstitial Cystitis Association (ICA)
      initiated an Internet-based survey on CAM. Respondents indicated whether they
      received an IC diagnosis and how long ago, whether they tried CAM, and who
      recommended it. On a 5-point scale, respondents rated 49 therapies. For
      respondents confirming a diagnosis, we used a chi-square goodness-of-fit test to
      assess which therapies were rated positively or negatively by a majority of
      patients who tried them. Using separate one-way analyses of variance, we assessed
      differences in mean perceived effectiveness among groups based on time since
      diagnosis and conducted post hoc tests, if necessary. Using chi-square tests, we
      explored the association of time since diagnosis with the use of CAM and the
      number of therapies tried. RESULTS: A total of 2,101 subjects responded to the
      survey; 1,982 confirmed an IC diagnosis. Most (84.2 %) had tried CAM, and 55 %
      said physicians had recommended CAM. Of those trying CAM, 82.8 % had tried diet
      or physical therapy and 69.2 % other therapies. Of the therapies, 22 were rated
      positively and 20 negatively; 7 were inconclusive. Therapies patients perceived
      to be helpful included dietary management and pain management adjuncts such as
      physical therapy, heat and cold, meditation and relaxation, acupuncture, stress
      reduction, exercise, and sleep hygiene. Many therapies worked better for those
      diagnosed recently than for those diagnosed long before. CONCLUSIONS: Randomized,
      placebo-controlled studies are needed to demonstrate which therapies may indeed
      control IC symptoms and help send research in new and productive directions.

PMID- 23149599
TI  - Asymptomatic microscopic hematuria in women requires separate guidelines.
AB  - The guidelines recently updated by the American Urological Association for the
      evaluation of asymptomatic microscopic hematuria (AMH) are based on data derived
      predominantly from men. They cannot be reliably applied to females as the
      epidemiology of AMH is gender dependent. The research on women in this area has
      been limited. It is incumbent on the experts in the field of female pelvic
      medicine to advance the science and develop management algorithms for AMH in
      women.

PMID- 23149600
TI  - 'Stroke-like syndrome' caused by intrathecal methotrexate in patients treated
      during the UKALL 2003 trial.

PMID- 23149601
TI  - Tube radial distribution of solvents observed in an aqueous ionic liquid mixed
      solution delivered into a capillary tube.
AB  - The tube radial distribution of solvents was observed in an aqueous ionic liquid
      mixed solution of 1-butyl-3-methylimidazolium chloride fed into a capillary tube.
      A phase diagram was constructed with 1-butyl-3-methylimidazolium chloride and
      potassium hydroxide, which included boundary curves between homogeneous and
      heterogeneous solutions at 15 and 20 degrees C. As an example, an aqueous ionic
      liquid mixed homogeneous solution, comprising the ratio of 1-butyl-3
      methylimidazolium chloride:potassium hydroxide (30.5:16.5 wt/wt%), which were
      positioned near the boundary at 20 degrees C, were delivered into a fused-silica
      capillary tube (75 MUm i.d., 110 cm length, 15 degrees C tube temperature) at a
      flow rate of 1.0 MUL min(-1). The homogeneous solution changed to a heterogeneous
      solution with two phases: the inner (the aqueous phase merely containing the
      ionic liquid) and the outer (the ionic liquid-rich) phases, in the capillary
      tube. The radial distribution of the solvents in the aqueous ionic liquid mixed
      solution was observed through a bright-light microscope-CCD camera system.

PMID- 23149602
TI  - Experimental investigations of trimer ion contributions in the low resolution
      mass spectrometry of hydrogen isotope mixtures.
AB  - This paper reports on some preliminary experimental results of a work in progress
      regarding a problem involving the quantitative analysis of hydrogen isotopes by
      mass spectrometry of low resolution: the triatomic (trimer) ions interferences
      with the isotopic hydrogen species having the same mass/charge. These results
      indicate that, in complex mixtures of hydrogen isotopes, trimer ions are strongly
      affected by the presence of other species, and a new approach that takes into
      account the destruction mechanism of trimer ions is necessary for a proper
      determination of their contributions.

PMID- 23149603
TI  - Placement of nanospace on an electrode for biosensing.
AB  - Electrical and electrochemical methods are well established as very useful
      techniques in the field of biosensing because they can easily handle signals and
      devices.  This paper provides an overview of biosensing using a nanometer-sized
      space functionally.  Placed effectively on the electrode, the nanospace offers
      several advantages, such as increased sensitivity, improved selectivity,
      decreased response time, and the potential for instrument miniaturization.  Given
      the impressive technological progress of nanospace biosensors and its growing
      impact on analytical science, this review offers an easy-to-understand
      presentation describing the history, recent advances, new methods, and future
      prospects of nanospace biosensors.

PMID- 23149604
TI  - Stable lipid bilayers based on micro- and nano-fabrication as a platform for
      recording ion-channel activities.
AB  - In this review, we will discuss our recent approaches for the formation of
      mechanically stable bilayer lipid membranes (BLMs) by combining with BLM
      formation and micro- and nano-fabrication techniques. BLMs were prepared across a
      microaperture fabricated in silicon (Si) chips or nanoporous alumina films using
      a minimized amount of organic solvent. Although BLMs spanned over the porous
      alumina film showed better electrical properties, such as background current
      noise and current transient, BLMs suspended in a thin Si(3)N(4) septum showed a
      much superior BLM stability. The BLMs showed tolerance to a high voltage of +/-1
      V, a membrane lifetime of >40 h, and tolerance to repetitive solution exchanges.
      Application to a drug screening system has been examined by using the human ether
      a-go-go-related gene (hERG) potassium channel as an illustrative example. The
      potentiality of the present system as a platform of the high-throughput analysis
      for ion-channel protein is also discussed.

PMID- 23149605
TI  - A pivot-hinge-style DNA immobilization method with adaptable surface
      concentration based on oligodeoxynucleotide-phosphorothioate chemisorption on
      gold surfaces.
AB  - The chemisorption of oligodeoxynucleotide phosphorothioate (s-oligo) is reported.
      A series of s-oligo DNAs was designed for use as capture probe DNA molecules. The
      s-oligo DNAs consist of the K-ras gene (5'-GGA GCT GGT GGC-3') and a dodecamer
      deoxyriboadenosine, both of which lie on either side of an s-oligo DNA sequence.
      By primarily focusing on the capture probe DNA having five-successive s-oligo
      sequences, e37, the immobilization chemistry of e37 was examined; atomic force
      microscopy achieved the direct visualization of individual molecules on Au(111)
      substrates, while a series of surface analyses, including IR, ellipsometry, and
      microgravimetry, showed that the s-oligo functional groups played a pivotal role
      in the surface-adlayer through the gold-thiol interaction. Interestingly, the
      amount of immobilization showed a definite relationship with the number of s
      oligo linkages introduced, which should be important to regulate the
      concentration of the capture probe DNA molecules on the surface. Some preliminary
      studies using ferrocene-modified complementary sequences indicated that
      electrochemical labeling and readouts were possible.

PMID- 23149606
TI  - Microviscosity of supercooled water confined within aminopropyl-modified
      mesoporous silica as studied by time-resolved fluorescence spectroscopy.
AB  - The fluorescence dynamics of rhodamine B (RhB) immobilized on the pore surface of
      aminopropyl (AP)-modified mesoporous silica (diameter of the silica framework,
      3.1 nm) was examined at temperatures between 293 and 193 K to study the
      microviscosity of supercooled water confined inside the pores. The mesoporous
      silica specimen with a dense AP layer (2.1 molecules nm(-2)) was prepared, and
      RhB isothiocyanate was covalently bound to part of the surface AP groups. The
      fluorescence lifetime of the surface RhB increased with decreasing temperature
      from 293 to 223 K, indicating that freezing of the confined water did not occur
      in this temperature range. The microviscosity of the supercooled confined water
      was evaluated from an analysis of the lifetime data based on a frequency
      dependent friction model.

PMID- 23149607
TI  - Development of an anti-analyte ion remover used for ion chromatography: Part 1.
      Examination of a device for anion analysis.
AB  - Herein, we report on the fabrication of a device for removing cations of an anti
      analyte ion contained in a sample and an eluent under an electric field.  The
      space in which the electrode is set on both sides of the device is separated into
      three cells using anion and cation exchange membranes.  Each of the cells is
      packed with either an anion or cation exchange resin.  Cation removal is
      performed by electrical regeneration, based on the electrokinetic phenomenon on
      both the surface of the ion exchange resins and the membranes.  It was verified
      that the developed device has a very low dead volume, and sufficient capacity for
      the continuous removal of cations from the sample and the eluent.  In addition,
      the detection sensitivity of ion chromatography (IC) was improved using this
      device as a suppressor, and a detection limit of anions on the sub-ppb order was
      achieved.

PMID- 23149608
TI  - Flow injection amperometric detection of sulfide using a prussian blue modified
      glassy carbon electrode.
AB  - This study investigates a new approach for the electrocatalytic determination of
      sulfide in a flow injection analysis (FIA) system using a Prussian blue modified
      glassy carbon electrode (PB/GCE). The results from experiments show that PB/GCE
      significantly enhances the electrocatalytic activity towards sulfide oxidation. A
      homemade flow electrochemical cell was used to perform the electrocatalytic
      determination of sulfide in the FIA system. The currents obtained from
      amperometric measurements in the FIA system at optimum conditions (carrier
      solution, pH 8.0; Britton-Robinson buffer solution containing 0.1 M KCl; flow
      rate, 1.4 mL/min; transmission tubing length, 10 cm; injection volume, 100 MUL;
      constant applied potential, +150 mV vs. Ag/AgCl/KClsat) were linearly correlated
      with the sulfide concentration. A calibration curve was obtained for sulfide
      concentrations in the range of 0.5 - 100 MUM. The detection limit was found to be
      0.3 MUM for the amperometric method. The proposed method was successfully applied
      to wastewater sample. Finally, results from sulfide measurements by PB/GCE were
      in good agreement with those obtained from the spectrophotometric method.

PMID- 23149609
TI  - Simple, rapid, and simultaneous assay of multiple carboxyl containing
      phytohormones in wounded tomatoes by UPLC-MS/MS using single SPE purification and
      isotope dilution.
AB  - An efficient simplified isotope dilution method was developed to determine four
      carboxyl containing phytohormones simultaneously in 200 mg of fresh tomato
      tissues using ultra high performance liquid chromatography-triple quadrupole mass
      spectrometry (UPLC-MS/MS) with negative electrospray ionization. The four
      phytohormones are indole-3-acetic acid (IAA), abscisic acid (ABA), jasmonic acid
      (JA), and salicylic acid (SA). Only one purification step of Oasis MAX solid
      phase extraction (SPE) was employed to enrich target phytohormones after crude
      extraction. In addition, two endogenous isomers of JA, (-)-JA and (+)-7-iso-JA,
      were separated directly. The validated method has been applied to monitor changes
      of JA, SA, IAA, and ABA in both local and systemic leaves of wild-type and
      transgenic 35S::prosystemin (35S::PS) tomato lines. Meanwhile, the JA burst
      amplified by the overexpressed prosystemin in 35S::PS was verified. Furthermore,
      the spatial and temporal changes of JA, SA, ABA, and IAA were analyzed.

PMID- 23149610
TI  - Characterization of certified reference material for the quantification of water
      in bioethanol.
AB  - The National Metrology Institute of Japan has issued a certified reference
      material of bioethanol (NMIJ CRM 8301-a) for the quantification of water,
      methanol, sulfur, and copper. This paper presents technical details for the
      characterization of the water in NMIJ CRM 8301-a. The characterization was
      performed using coulometric and volumetric Karl-Fischer (KF) titrations. To
      reduce moisture absorption, sample handling and KF titration were performed in a
      glove box under a dried nitrogen atmosphere. In addition, a rubber cap with a
      three-way valve was attached to the ampoule immediately after opening so as to
      minimize the influence of moisture. Sample aliquots were obtained using a gas
      tight microsyringe through the valve, and injected into the KF cell as soon as
      possible. The certified value of water obtained from coulometric and volumetric
      KF titrations was 1.688 mg g(-1), and the expanded uncertainty (coverage factor,
      k = 2) was 0.028 mg g(-1). This CRM would be suitable for the monitoring of water
      in bioethanol and similar matrices.

PMID- 23149611
TI  - Four-way self-weighted alternating normalized residue fitting algorithm with
      application for the analysis of serotonin in human plasma.
AB  - A novel algorithm, four-way self-weighted alternating normalized residue fitting
      (SWANRF), which is an extension of its three-way form, for the decomposition of
      quadrilinear data with new weight factors, was proposed and applied to the
      quantitative analysis of serotonin contents in plasma samples. It was observed
      that the third-order calibration could not only retain a "second-order advantage"
      and but also obtain other advantages. The introduction of a fourth mode can
      relieve the serious problem of collinearity, which seems to be one of the "third
      order advantages". The proposed algorithm shows great potential as a promising
      alternative for the third-order calibration of a four-way data array by
      contrasting with four-way parallel factor analysis (four-way PARAFAC).
      Furthermore, both algorithms mentioned above were utilized to analyze the 5
      hydroxytryptamine (serotonin) contents in plasma samples by obtaining four-way
      array (excitation-emission-pH-sample) data, and produced satisfactory results.
      The serotonin contents in plasma samples obtained by using four-way SWANRF and
      four-way PARAFAC were 0.324 +/- 0.005 and 0.348 +/- 0.006 nmol mL(-1),
      respectively.

PMID- 23149612
TI  - Evaluation on the stability of Hg in ABS disk CRM during measurements by
      wavelength dispersive X-ray fluorescence spectrometry.
AB  - The stability of Hg in an acrylonitrile-butadiene-styrene disk certified
      reference material (ABS disk CRM, NMIJ CRM 8116-a) during measurements by
      wavelength dispersion X-ray fluorescence (WD-XRF) analysis was evaluated in this
      study. The XRF intensities of Hg (L(alpha)) and Pb (L(alpha)) as well as the XRF
      intensity ratios of Hg (L(alpha))/Pb (L(alpha)) observed under different X-ray
      tube current conditions as well as their irradiation time were examined to
      evaluate the stability of Hg in the ABS disk CRM. The observed XRF intensities
      and the XRF intensity ratios for up to 32 h of measurements under 80 mA of X-ray
      tube current condition were constant, even though the surface of the ABS disk CRM
      was charred by the X-ray irradiation with high current for a long time. Moreover,
      the measurements on Hg and Pb in the charred disks by an energy dispersive XRF
      (ED-XRF) spectrometer showed constant XRF intensity ratios of Hg (L(alpha))/Pb
      (L(alpha)). From these results, Hg in the ABS disk CRM was evaluated to be
      sufficiently stable for XRF analysis.

PMID- 23149613
TI  - Control of the electrostatic effect on DAM-adsorbent for the water-soluble
      compounds by HPLC.
AB  - The effect of the mobile phase pH on the control of the electrostatic interaction
      was evaluated on a column packed with water-holding adsorbent on which
      diallylamine-maleic acid copolymers were immobilizing. The adsorbent showed
      extraordinary retention behaviors of water-soluble solutes under acidic
      conditions, however, their behavior became stable along with increasing pH.
      Hydrating water contents tended to level off at pH above 8. Thus, the
      electrostatic interaction with the stationary phase can be controlled by
      adjusting the mobile phase pH above 8. In this region, the retention of water
      soluble solutes appears to be mainly governed by the hydrophilic partition
      interaction.

PMID- 23149614
TI  - Determination of molybdate in environmental water by ion chromatography coupled
      with a preconcentration method employing a selective chelating resin.
AB  - A simple and sensitive suppressed ion chromatography (IC) method with
      conductivity detection for the determination of molybdate in environmental water
      is proposed. Molybdate in highly saline water was extracted and preconcentrated.
      Preconcentration was accomplished by using a chelating resin using a chelating
      resin immobilized with carboxymethylated polyethylenimine (Presep((r))
      PolyChelate). This resin is able to trap a variety of metal elements without any
      interference of alkali and alkaline-earth metals. A 30-mL volume of brackish
      water was adjusted for appropriate pH and then flushed through 100 mg of the
      chelating resin. Molybdate concentrated on the resin could be easily eluted with
      6 mL of 0.1 M NaOH. A large volume injection method for IC was achieved with in
      line neutralization of the effluent. The determination of 0.6 MUg L(-1) molybdate
      in highly saline water was made possible with a 500-MUL injection. Samples of
      brackish water were taken at various distances from the river mouth. The
      determined concentrations of molybdate correlated closely with concentrations of
      chloride.

PMID- 23149615
TI  - Glucose transporter 1 (GLUT1) and its emerging role as a significant prognostic
      marker in systemic malignancies.

PMID- 23149616
TI  - Late optic neuropathy in propionic acidemia following surgical intervention.

PMID- 23149617
TI  - Surgical management of an optic nerve glioma with perineural arachnoidal
      gliomatosis growth pattern.
AB  - We describe a vision sparing surgical approach for optic nerve glioma. A 7-year
      old girl experienced declining academic performance and social withdrawal
      attributed to progressive disfiguring proptosis. Three years earlier, she had
      undergone a limited biopsy, a course of chemotherapy, and orbital radiation
      therapy for a right optic nerve glioma with perineural arachnoidal gliomatosis
      (PAG). Because of marked proptosis, another surgery was performed via a lateral
      orbitotomy. After cutting a window in the thickened dura of the optic nerve,
      rouge colored spongy tissue was suctioned from the subarachnoid space. Small,
      more solidified areas were excised with unipolar cautery. Care was taken to avoid
      identifiable blood vessels and the optic nerve, and approximately 60%-70% of the
      tumor was removed. The dural window was approximated with interrupted sutures.
      Postoperatively, there was 9 mm reduction in right proptosis and visual acuity
      improved to from 20/70 to 20/60. This case illustrates the possibility of
      debulking optic nerve gliomas without sacrificing vision. It should be stressed
      that this technique is only applicable to gliomas with PAG and the durability of
      the surgical benefit is unknown.

PMID- 23149619
TI  - [To Prof. Dr. Johann H. Karstens on the occasion of his retirement].

PMID- 23149618
TI  - Radiotherapy with or without chemotherapy in the treatment of anal cancer: 20
      year experience from a single institute.
AB  - PURPOSE: To report the efficacy and toxicity of radio(chemo)therapy (RCT) in the
      management of squamous cell anal carcinoma (SQ-AC) and to evaluate the prognostic
      factors influencing the outcomes. PATIENTS AND METHODS: A consecutive cohort of
      138 patients with cT1-4, cN0-3, cM0 SQ-AC were treated with RCT between 1988 and
      2011 at our department. Median follow-up time for surviving patients from the
      start of RCT was 98 months (range, 1-236 months). Patients were treated with a
      median radiation dose of 56 Gy (range, 4-61 Gy). Concurrent chemotherapy was
      administered to 119 patients (86%). RESULTS: The survival rates at 2, 5, and 10
      years were 88 +/- 3, 82 +/- 4, and 59 +/- 6%, respectively, with a median overall
      survival (OS) of 167 months. The cumulative incidence for local recurrence at 2
      and 5 years was 8 +/- 2 and 11 +/- 3%, respectively. The median disease-free
      survival (DFS) and colostomy-free survival (CFS) times were 132 and 135 months,
      respectively. In 19 patients (14%), a distant metastasis was diagnosed after a
      median time of 19 months. In the multivariate analysis, UICC (International Union
      Against Cancer) stage I-II, female gender, Eastern Cooperative Oncology Group
      (ECOG) performance status of 0-1, and good/moderate histologic differentiation
      (G1-2) were significantly associated with a better OS, DFS, and CFS. Conformal
      radiotherapy planning techniques were significantly associated with a lower
      cumulative incidence of local recurrence (11 +/- 3% vs. 38 +/- 19% at 5 years, p
      = 0.006). A higher radiation dose beyond 54 Gy was not associated with an
      improvement in outcome, neither for smaller-(T1/T2) nor for larger tumors
      (T3/T4). CONCLUSION: RCT leads to excellent outcomes-especially in patients with
      stage I/II and G1/G2 tumors-with acceptable toxicity. The probable advantages of
      high-dose radiotherapy should be considered carefully against the risk of a
      higher rate of toxicity. Future studies are needed to investigate the role of a
      more intensified (systemic) treatment for patients with unfavorable prognostic
      factors such as T3/T4, N+, and/or poor cell differentiation.

PMID- 23149622
TI  - Comparison of brown and white adipose tissue fat fractions in ob, seipin, and
      Fsp27 gene knockout mice by chemical shift-selective imaging and (1)H-MR
      spectroscopy.
AB  - Brown adipose tissue (BAT) plays a key role in thermogenesis to protect the body
      from cold and obesity. White adipose tissue (WAT) stores excess energy in the
      form of triglycerides. To better understand the genetic effect on regulation of
      WAT and BAT, we investigated the fat fraction (FF) in two types of adipose
      tissues in ob/ob, human BSCL2/seipin gene knockout (SKO), Fsp27 gene knockout
      (Fsp27(-/-)), and wild-type (WT) mice in vivo using chemical shift selective
      imaging and (1)H-MR spectroscopy. We reported that the visceral fat volume in WAT
      was significantly larger in ob/ob mice, but visceral fat volumes were lower in
      SKO and Fsp27(-/-) mice compared with WT mice. BAT FF was significantly higher in
      ob/ob mice than the WT group and similar to that of WAT. In contrast, WAT FFs in
      SKO and Fsp27(-/-) mice were lower and similar to that of BAT. The adipocyte size
      of WAT in ob/ob mice and the BAT adipocyte size in ob/ob, SKO, and Fsp27 mice
      were significantly larger compared with WT mice. However, the WAT adipocyte size
      was significantly smaller in SKO mice than in WT mice. Positive correlations were
      observed between the adipocyte size and FFs of WAT and BAT. These results
      suggested that smaller adipocyte size correlates with lower FFs of WAT and BAT.
      In addition, the differences in FFs in WAT and BAT measured by MR methods in
      different mouse models were related to the different regulation effects of ob,
      seipin, or Fsp27 gene on developing WAT and BAT.

PMID- 23149620
TI  - The opposite roles of glucocorticoid and alpha1-adrenergic receptors in stress
      triggered apoptosis of rat Leydig cells.
AB  - The stress-induced initiation of proapoptotic signaling in Leydig cells is
      relatively well defined, but the duration of this signaling and the mechanism(s)
      involved in opposing the stress responses have not been addressed. In this study,
      immobilization stress (IMO) was applied for 2 h daily, and animals were
      euthanized immediately after the first (IMO1), second (IMO2), and 10th (IMO10)
      sessions. In IMO1 and IMO2 rats, serum corticosterone and adrenaline were
      elevated, whereas serum androgens and mRNA transcription of insulin-like factor-3
      in Leydig cells were inhibited. Reduced oxygen consumption and the mitochondrial
      membrane potential coupled with a leak of cytochrome c from mitochondria and
      increased caspase-9 expression, caspase-3 activity, and number of apoptotic
      Leydig cells was also observed. Corticosterone and adrenaline were also elevated
      in IMO10 rats but were accompanied with a partial recovery of androgen secretion
      and normalization of insulin-like factor-3 transcription coupled with increased
      cytochrome c expression, abolition of proapoptotic signaling, and normalization
      of the apoptotic events. Blockade of intratesticular glucocorticoid receptors
      diminished proapoptotic effects without affecting antiapoptotic effects, whereas
      blockade of intratesticular alpha(1)-adrenergic receptors diminished the
      antiapoptotic effects without affecting proapoptotic effects. These results
      confirmed a critical role of glucocorticoids in mitochondria-dependent apoptosis
      and showed for the first time the relevance of stress-induced upregulation of
      alpha(1)-adrenergic receptor expression in cell apoptotic resistance to
      repetitive IMOs. The opposite role of two hormones in control of the apoptotic
      rate in Leydig cells also provides a rationale for a partial recovery of androgen
      production in chronically stressed animals.

PMID- 23149623
TI  - Improved glycemic control in mice lacking Sglt1 and Sglt2.
AB  - Sodium-glucose cotransporter 2 (SGLT2) is the major, and SGLT1 the minor,
      transporter responsible for renal glucose reabsorption. Increasing urinary
      glucose excretion (UGE) by selectively inhibiting SGLT2 improves glycemic control
      in diabetic patients. We generated Sglt1 and Sglt2 knockout (KO) mice,
      Sglt1/Sglt2 double-KO (DKO) mice, and wild-type (WT) littermates to study their
      relative glycemic control and to determine contributions of SGLT1 and SGLT2 to
      UGE. Relative to WTs, Sglt2 KOs had improved oral glucose tolerance and were
      resistant to streptozotocin-induced diabetes. Sglt1 KOs fed glucose-free high-fat
      diet (G-free HFD) had improved oral glucose tolerance accompanied by delayed
      intestinal glucose absorption and increased circulating glucagon-like peptide-1
      (GLP-1), but had normal intraperitoneal glucose tolerance. On G-free HFD, Sglt2
      KOs had 30%, Sglt1 KOs 2%, and WTs <1% of the UGE of DKOs. Consistent with their
      increased UGE, DKOs had lower fasting blood glucose and improved intraperitoneal
      glucose tolerance than Sglt2 KOs. In conclusion, 1) Sglt2 is the major renal
      glucose transporter, but Sglt1 reabsorbs 70% of filtered glucose if Sglt2 is
      absent; 2) mice lacking Sglt2 display improved glucose tolerance despite UGE that
      is 30% of maximum; 3) Sglt1 KO mice respond to oral glucose with increased
      circulating GLP-1; and 4) DKO mice have improved glycemic control over mice
      lacking Sglt2 alone. These data suggest that, in patients with type 2 diabetes,
      combining pharmacological SGLT2 inhibition with complete renal and/or partial
      intestinal SGLT1 inhibition may improve glycemic control over that achieved by
      SGLT2 inhibition alone.

PMID- 23149621
TI  - Angiotensin II type 2 receptor promotes adipocyte differentiation and restores
      adipocyte size in high-fat/high-fructose diet-induced insulin resistance in rats.
AB  - This study was aimed at establishing whether specific activation of angiotensin
      II (ANG II) type 2 receptor (AT2R) modulates adipocyte differentiation and
      function. In primary cultures of subcutaneous (SC) and retroperitoneal (RET)
      preadipocytes, both AT2R and AT1R were expressed at the mRNA and protein level.
      Cells were stimulated with ANG II or the AT2R agonist C21/M24, alone or in the
      presence of the AT1R antagonist losartan or the AT2R antagonist PD123,319. During
      differentiation, C21/M24 increased PPARgamma expression in both RET and SC
      preadipocytes while the number of small lipid droplets and lipid accumulation
      solely increased in SC preadipocytes. In mature adipocytes, C21/M24 decreased the
      mean size of large lipid droplets. Upon abolishment of AT2R expression using AT2R
      targeted shRNAs, expressions of AT2R, aP2, and PPARgamma remained very low, and
      cells were unable to differentiate. In Wistar rats fed a 6-wk high-fat/high
      fructose (HFHF) diet, a significant shift toward larger adipocytes was observed
      in RET and SC adipose tissue depots. C21/M24 treatments for 6 wk restored normal
      adipocyte size distribution in both these tissue depots. Moreover, C21/M24 and
      losartan decreased hyperinsulinemia and improved insulin sensitivity impaired by
      HFHF diet. A strong correlation between adipocyte size area and glucose infusion
      rate during euglycemic-hyperinsulinemic clamp was observed. These results
      indicate that AT2R is involved in early adipocyte differentiation, while in
      mature adipocytes and in a model of insulin resistance AT2R activation restores
      normal adipocyte morphology and improves insulin sensitivity.

PMID- 23149624
TI  - Current concepts in refractory migraine.
AB  - OPINION STATEMENT: The Refractory or Intractable Migraine (RM) patient has long
      been a challenge to all healthcare providers (HCP). Headache specialists have
      recognized this sub group of patients who remain refractory to treatment. Despite
      this recognition, there are no formal criteria that characterize RM. This article
      will attempt to provide treatment approaches, some scientifically based and
      others that are empiric. A reasonable goal is to lessen disability. Combining the
      various modalities will improve the chances for successful treatment. The
      foundation of treatment is an emphasis on wellness. This includes optimizing
      mood, minimizing stress, practicing good sleep hygiene, and avoiding triggers.
      All comorbid factors should be addressed, including sleep and mood disorders,
      chronic neck pain, and obesity. Preventive treatment is necessary in the majority
      of patients, and a plan for "rescue" approaches is essential. Avoiding medication
      overuse, particularly narcotics, is advisable. Additional options for treatment
      include onabotulinumtoxinA, and more invasive modalities, such as
      neurostimulation. Adjunct treatment including supplements and relaxation may also
      be considered. Keeping a headache calendar is almost mandatory in management with
      attention to particular headache triggers, patterns and medication overuse (MOH).
      A trusting physician-patient relationship is also very important and will enhance
      compliance and foster communication. Patients often lapse from the management
      plan and the treating physician should be open minded about continuing care. RM
      is a long-term disease and requires close physician-patient interaction and
      cooperation for management of the problem. In those RM patients with multiple
      comorbidities, a multidisciplinary team should optimize management.

PMID- 23149626
TI  - The influence of carbon content on the structure and properties of MoS(x)C(y)
      photocatalysts for light-driven hydrogen generation.
AB  - Carbon containing nano-sized molybdenum sulfide composites (MoS(x)C(y)) obtained
      by thermal decomposition reactions of (R(4)N)(2)MoS(4) (R = -H (C(0)), -CH(3)
      (C(1)), -C(3)H(7) (C(3)), and -C(6)H(13) (C(6))) show promising performance in
      visible-light driven photocatalytic hydrogen generation.

PMID- 23149625
TI  - Improved growth media and culture techniques for genetic analysis and assessment
      of biomass utilization by Caldicellulosiruptor bescii.
AB  - Methods for efficient growth and manipulation of relatively uncharacterized
      bacteria facilitate their study and are essential for genetic manipulation. We
      report new growth media and culture techniques for Caldicellulosiruptor bescii,
      the most thermophilic cellulolytic bacterium known. A low osmolarity defined
      growth medium (LOD) was developed that avoids problems associated with
      precipitates that form in previously reported media allowing the monitoring of
      culture density by optical density at 680 nm (OD(680)) and more efficient DNA
      transformation by electroporation. This is a defined minimal medium and does not
      support growth when a carbon source is omitted, making it suitable for selection
      of nutritional markers as well as the study of biomass utilization by C. bescii.
      A low osmolarity complex growth medium (LOC) was developed that dramatically
      improves growth and culture viability during storage, making it a better medium
      for routine growth and passaging of C. bescii. Both media contain significantly
      lower solute concentration than previously published media, allowing for
      flexibility in developing more specialized media types while avoiding the issues
      of growth inhibition and cell lysis due to osmotic stress. Plating on LOD medium
      solidified by agar results in ~1,000-fold greater plating efficiency than
      previously reported and allows the isolation of discrete colonies. These new
      media represent a significant advance for both genetic manipulation and the study
      of biomass utilization in C. bescii, and may be applied broadly across the
      Caldicellulosiruptor genus.

PMID- 23149627
TI  - Sperm ultrastructure in the diatoms Melosira and Thalassiosira and the
      significance of the 9 + 0 configuration.
AB  - The most complete account to date of the ultrastructure of flagellate cells in
      diatoms is given for the sperm of Thalassiosira lacustris and Melosira
      moniliformis var. octogona, based on serial sections. The sperm are
      uniflagellate, with no trace of a second basal body, and possess a 9 + 0 axoneme.
      The significance of the 9 + 0 configuration is discussed: lack of the central
      pair microtubules and radial spokes does not compromise the mastigoneme-bearing
      flagellum's capacity to perform planar beats and thrust reversal and may perhaps
      be related to sensory/secretory function of the sperm flagellum during
      plasmogamy. The basal bodies of diatoms are confirmed to contain doublets rather
      than triplets, which may correlate with the absence of some centriolar proteins
      found in most cells producing active flagella. Whereas Melosira possesses a
      normal cartwheel structure in the long basal body, no such structure is present
      in Thalassiosira, which instead possesses 'intercalary fibres' linking the basal
      body doublets. No transitional helices or transitional plates are present in
      either species studied. Cones of microtubules are associated with the basal body
      and partially enclose the nucleus in M. moniliformis and T. lacustris. They do
      not appear to be true microtubular roots and may arise through transformation of
      the meiosis II spindle. A close association between cone microtubules and tubules
      containing mastigonemes may indicate a function in intracellular mastigoneme
      transport. No correlation can yet be detected between methods of spermatogenesis
      and phylogeny in diatoms, contrary to previous suggestions.

PMID- 23149628
TI  - Formation of one-dimensional Ag-Au solid solution colloids with Au nanorods as
      seeds, their alloying mechanisms, and surface plasmon resonances.
AB  - In this work, one dimensional (1D) Ag-Au solid solution nanoalloys were
      synthesized by rapidly diffusing Ag into the preformed Au nanorod (AuNR) seeds at
      ambient temperature in aqueous solution. By varying the molar ratio of AgCl/AuNR
      (in gold atoms), two kinds of 1D Ag-Au alloy nanostructures with a narrow size
      distribution--AgAu nanowires and Ag(33)Au(67) nanorods--could be obtained in high
      yields when NaCl and polyvinylpyrrolidone (PVP) were used as an additive and
      capping reagent, respectively. Based on HRTEM imaging combined with a series of
      control experiments, it is conceivable that vacancy/defect-motivated
      interdiffusion of Ag and Au atoms coupled with oxidative etching is a crucial
      stage in the mechanism responsible for this room-temperature alloying process,
      and the subsequent conjugation of the fused Ag-Au alloyed nanostructures is
      associated with the formation of the AgAu nanowires. The resulting 1D Ag-Au
      nanoalloys form stable colloidal dispersions and show unique localized surface
      plasmon resonance (LSPR) peaks in the ensemble extinction spectra.

PMID- 23149629
TI  - Vibrational modes of GaN nanowires in the gigahertz range.
AB  - Brillouin-light-scattering measurements and finite-element modeling of
      vibrational spectra in the range of 5-40 GHz are presented for an array of
      monocrystalline GaN nanowires with hexagonal cross sections. Analysis of the
      spectra is substantially complicated by the presence of a distribution of
      nanowire diameters. The measurements and calculations reveal a variety of modes
      with simple flexural, higher-order flexural, approximately 'plane-strain',
      approximately longitudinal and torsional displacement patterns that are similar
      to the corresponding modes of isotropic cylinders. The largest peaks in the
      spectra with acoustic angular wavenumbers in the range of 4 to ~15 MUm(-1) were
      determined to arise from modes with relatively large transverse displacements,
      consistent with inelastic light scattering arising predominantly from surface
      ripple. These dominant modes have finite frequencies in the limit of zero
      wavenumber, corresponding to transverse standing waves. At higher wavenumbers,
      the spectra provide evidence for increased scattering through elasto-optic
      coupling, especially with respect to the emergence of a peak from a mode
      analogous to the longitudinal guided modes of thin films.

PMID- 23149630
TI  - Linking genome annotation projects with genetic disorders using ontologies.
AB  - Genome sequencing projects generate vast amounts of data of a wide variety of
      types and complexities, and at a growing pace. Traditionally, the annotation of
      such sequences was difficult to share with other researchers. Despite the fact
      that this has improved with the development and application of biological
      ontologies, such annotation efforts remain isolated since the amount of
      information that can be used from other annotation projects is limited. In
      addition to this, they do not benefit from the translational information
      available for the genomic sequences. In this paper, we describe a system that
      supports genome annotation processes by providing useful information about
      orthologous genes and the genetic disorders which can be associated with a gene
      identified in a sequence. The seamless integration of such data will be
      facilitated by an ontological infrastructure which, following best practices in
      ontology engineering, will reuse existing biological ontologies like Sequence
      Ontology or Ontological Gene Orthology.

PMID- 23149631
TI  - The role of 1-h physical activity every day in preventing obesity in adolescents
      in Shandong, China.
AB  - Several studies have reported that physical inactivity and sedentary lifestyle
      are associated with being overweight and obese in children and adults. A new
      policy of 1-h physical activity (PA) every day was released by the Chinese
      government. The present study examined the role of 1-h PA every day in preventing
      obesity in adolescents in Shandong, China. A total of 29,030 students (14,578
      boys and 14,452 girls) aged 10-18 years participated in this study. Height,
      weight, waist circumference (WC), and skinfold thickness (SFT) of all subjects
      were measured; body mass index (BMI) of adolescents was calculated from their
      height and weight, and the prevalence of overweight and obesity was obtained
      according to the International Obesity Task Force cutoffs. All subjects were
      divided into two groups. Group 1 had a PA of more than 1 h/day while group 2 had
      less than 1 h/day. Comparisons of BMI, WC, SFT, and prevalences of overweight and
      obesity between the two groups were made. The overall percentages of students in
      group 1 were 34.29 % in boys and 30.15 % in girls. The prevalences of overweight
      and obesity for both boys and girls were all significantly lower in group 1 than
      in group 2 in all age categories. In conclusion, 1-h PA every day has a
      beneficial effect in preventing obesity in adolescents in Shandong, China. These
      observations highlight the importance of PA in the prevention of overweight and
      obesity in adolescents.

PMID- 23149632
TI  - Neonatal respiratory support strategies in the intensive care unit: an Italian
      survey.
AB  - We carried out a survey of current practices of neonatal respiratory support in
      neonatal intensive care units (NICUs) in Italy with the aim of comparing the
      current reality with evidence from the literature. We sent a questionnaire by
      email to the 103 level III neonatal units in Italy. There was a 61 % (73/120)
      response rate to the questionnaire. We found that synchronized intermittent
      positive pressure ventilation is mostly used in infants in the acute phase of
      respiratory distress syndrome (RDS), while the majority of the units prefer
      volume-targeted ventilation for those in the weaning phase. Nasal continuous
      positive airway pressure is the most commonly used non-invasive mode of
      respiratory support, both in the acute and post-extubation phase of RDS.
      Surfactant is mainly given as rescue treatment. Infants receive caffeine before
      extubation and analgesia under mechanical ventilation, while post-natal steroids
      are given after the first week of life in the majority of the units. In
      conclusion, respiratory support strategies in Italian NICUs are frequently
      evidence-based. However, since there are areas where this does not occur, we
      suggest that focused interventions take place on these areas to help improve
      clinical practice and increase their adherence to evidence-based medical
      criteria.

PMID- 23149633
TI  - Juvenile Systemic Lupus Erythematosus: neuropsychiatric manifestations.
AB  - Juvenile Systemic Lupus Erythematosus (jSLE) is a chronic and multisystemmic
      autoimmune disease, which appears before 16 years old with an incidence of 10 to
      20 cases per 100,000 children. The clinical spectrum of jSLE can be quite
      variable. The most common symptoms are constitutional, followed by the cutaneous,
      musculoskeletal, renal, and neuropsychiatric involvement. Neuropsychiatric
      involvement in jSLE has a prevalence ranging from 20 to 50.9% and results in
      significant morbidity and mortality. The most common clinical manifestations of
      juvenile neuropsychiatric SLE (NPSLE) are headache, cognitive dysfunction, mood
      disturbances and seizures. The pathophysiology of juvenile NPSLE is not yet fully
      known, but immunological and inflammatory factors, such as autoantibodies,
      cytokines and prothrombotic states are widely described. The role of
      autoantibodies in the onset of specific clinical manifestations has also been
      recognized. Juvenile NPSLE manifestations are often difficult to diagnose. In
      addition to semiological aspects, the study and validation of neuropsychological
      testing and neurocognitive assessment for the juvenile SLE population are
      essential. The role of advanced imaging techniques should be explored. The
      treatment of juvenile NPSLE must be individualized according to the type and
      severity of clinical manifestations, relying on symptomatic therapy,
      anticoagulants or steroids. New therapeutic approaches, including biotherapies
      need controlled randomized trials for further validation. This article aims to
      review the pathogenesis, clinical manifestations, diagnosis and treatment of
      juvenile NPSLE.

PMID- 23149634
TI  - [Validity and reliability of the Portuguese version of the Pain Coping
      Inventory].
AB  - OBJECTIVE: To analyze the validity and reliability of the Portuguese version of
      the Pain Coping Inventory (PCI) in order to perform a cultural adaptation to
      permit its use in Portuguese population of non-oncological chronic pain patients.
      METHODS: The PCI was translated to Portuguese and then again to English; moreover
      a spoken reflection was made. 180 participants with clinical diagnosis associated
      to chronic pain (namely, fibromyalgia and rheumatoid arthritis) were asked to
      fill in the self-report measure. Procedures of exploratory factorial analysis,
      confirmatory factorial analysis, and internal consistency were performed.
      RESULTS: Based on the methodological procedures, results have shown evidence of a
      factorial structure comprised by five factors which assess distinct chronic pain
      coping strategies namely, withdrawal, worrying, distraction, pain transformation,
      and reducing demands. CONCLUSIONS: The Portuguese version of PCI has shown
      evidence of validity and reliability which supports the relevance of its use in
      both research and clinical context.

PMID- 23149635
TI  - Finding Rheumatoid Arthritis Impact on Life (FRAIL Study): economic burden.
AB  - INTRODUCTION: The economic impact of rheumatoid arthritis (RA) is related with
      the costs supported by the society. It is of the utmost importance to estimate
      the costs of RA in Portugal in order to access its true social impact and improve
      the clinical management of this disease. OBJECTIVES: To determine the yearly
      direct and indirect costs of RA supported by the society in Portugal. METHODS:
      Observational, cross-sectional study with collection of retrospective data,
      involving patients with RA, diagnosed accordingly to 1987 American College of
      Rheumatology (ACR) criteria, independently of disease stage, with attendance to a
      specialist visit between October and December 2009 in a Rheumatology Clinic in
      Portugal. Data were obtained through the fulfillment of medical and patient
      questionnaires. Data being covered included socio-demographic and clinical
      characteristics and health resources. The societal perspective was considered
      including direct and indirect costs. Unitary costs were obtained from official
      national sources. RESULTS: The FRAIL study included 353 patients, 84% females,
      with an average age of 59 (range: 23-85 years). In the previous year: 97.2% of
      patients had a Rheumatology appointment (average: 4) and 35.6% a GP appointments
      (average: 6); 8.2% were hospitalized at least once, 9.3% had an urgency admission
      and 41.4% went to the day hospital. Most of the patients (96.0%) were on DMARD;
      94.3% performed routine exams; 35.7% had rehabilitation treatments; 21.4% had
      alternative medicine treatments; 5.7% needed house adaptations; 9.3% needed
      prosthesis; 5.1% needed permanent home support, 2.9% partial; 31% of the patients
      referred sick leave because of RA. We estimate that the annual mean cost of
      treating one RA patient in Portugal is about 3.415 ?, of which 77.3%, 9.6% and
      11.4%, corresponds to direct medical, direct non-medical and indirect cost,
      respectively. Total cost of the disease increase with disease activity. RA in
      remission has an average cost of 2.205 ?/patient/year versus 5.634 ? in high
      activity RA. CONCLUSIONS: Results of the FRAIL study allow a better understanding
      of the real economic impact of RA for society, which increased very significantly
      in the last 10 years. If we consider 35,000 patients with RA in Portugal, the
      annual cost would be 119,525,000 ? per year.

PMID- 23149636
TI  - Autoantibodies are not associated with familial mediterranean fever.
AB  - OBJECTIVE: It has been suggested that Mediterranean fever (MEFV) gene mutations
      are also seen in certain autoimmune diseases and are related to severity of the
      disease activity. As most of the clinical symptoms of these inflammatory diseases
      are related to autoantibody positivity, we assessed autoantibody prevalence in
      patients with Familial Mediterranean fever (FMF) and investigated the
      relationship between clinical involvement of FMF and the autoantibodies. There
      are a few studies on this subject with conflicting results. PATIENTS AND METHODS:
      Fifty patients with FMF without attack and 27 healthy controls were enrolled to
      the study. Clinical characteristics of the patient group were questioned.
      Rheumatoid factor (RF), anti-cyclic citrullinated peptide (anti-CCP) values,
      Fluorescent antinuclear antibody (ANA), extractable nuclear antigen (ENA) profile
      was studied in both groups. RESULTS: No statistically significant difference was
      found in ANA, ENA profile, anti-CCP, and RF positivity between the groups
      (p>0.05). There was no relationship between the autoantibodies and the clinical
      status in patients with FMF. MEFV gene mutations were identified in 98% of the
      FMF patients. CONCLUSION: In conclusion, autoantibody positivity is similar to
      the healthy population in FMF. Although MEFV mutations affect clinical course in
      other autoantibody mediated diseases, it is not related to autoantibody formation
      in FMF.

PMID- 23149637
TI  - Anti-Ro antibodies in rheumatoid arthritis.
AB  - BACKGROUND: Some autoantibodies are associated with peculiar clinical findings.
      Patients with rheumatoid arthritis (RA) may have anti-Ro antibodies. OBJECTIVE:
      To study prevalence and clinical associations of anti-Ro antibodies in RA
      patients. METHODS: We studied 385 patients with RA for anti-Ro by Elisa testing
      and for clinical profile, functional assessment, DAS-28 4v. (ESR), extra
      articular manifestations, thyroid function, autoantibodies and treatment.
      RESULTS: The prevalence of anti-Ro was 8.31%. There was no significant difference
      in sex distribution, HAQ, DAS-28 or functional classification in patients with
      positive anti-Ro (p=ns). Patients with anti-Ro were younger at diagnosis
      (p=0.02). Analyzing extra-articular disorders we found a greater prevalence of
      cardiac valvular lesions (p<0.001) in patients with anti-Ro antibodies. No
      differences were found in other extra-articular manifestations, associated
      hypothyroidism, amyloidosis, treatment requirements, presence of rheumatoid
      factor (RF) or anti citrullinated protein antibodies (ACPA). CONCLUSIONS: We
      conclude that in RA patients with anti-Ro have disease onset at an earlier age.
      Anti-Ro may be a risk factor for the development of cardiac valvular lesions.
      There was no association between this antibody and thyroid disease, amyloidosis
      and treatment needs.

PMID- 23149638
TI  - Lack of association between carotid intima-media wall thickness and carotid
      plaques and markers of endothelial cell activation in rheumatoid arthritis
      patients undergoing anti-TNF therapy.
AB  - INTRODUCTION: To determine the relationship between biomarkers of endothelial
      cell activation, and carotid artery intima-media wall thickness (IMT) and
      plaques, two surrogate markers of atherosclerosis, in a series of rheumatoid
      arthritis (RA) patients undergoing anti-TNF therapy. METHODS: 29 consecutive
      Spanish patients who fulfilled the 1987 American College of Rheumatology
      classification criteria for RA, had no history of cardiovascular (CV) disease,
      and had at least one year of follow-up after disease diagnosis were selected. All
      patients were undergoing anti-TNF-infliximab therapy because of severe disease
      refractory to conventional disease modifying antirheumatic drugs. Carotid
      ultrasonography was performed to determine IMT and carotid plaques. Levels of
      sICAM-3, sICAM-1, sVCAM-1, sPselectin and sE-selectin were assessed by ELISA
      immediately before an infusion of infliximab. RESULTS: The median disease
      duration was 14 years. Despite infliximab, no patient experienced a disease
      remission (DAS28: median 4.17). Only a marginally significant correlation between
      sVCAM-1 and carotid IMT was observed when both total correlation using Spearman
      correlation coefficient (p= 0.08) or partial correlation adjusting for sex, age
      at the time of study, disease duration, rheumatoid factor, and classic CV risk
      factors was performed (p= 0.09). Also, no association between presence of carotid
      plaques and levels of biomarkers of endothelial cell activation was observed.
      CONCLUSION: In long-standing RA patients without CV disease undergoing anti-TNF
      therapy no association between levels of soluble markers of endothelial cell
      activation and carotid ultrasonography abnormalities was observed. Further
      studies are needed to establish the best tools to be used in the assessment of CV
      risk of RA.

PMID- 23149639
TI  - [Portuguese recommendations for pain management by pharmocotherapy in
      inflammatory arthritis].
AB  - OBJECTIVES: To develop Portuguese evidence-based recommendations for pain
      management by pharmocotherapy in inflammatory arthritis. METHODS: The Portuguese
      project was integrated in the multinational 3E Initiative (Evidence, Expertise,
      Exchange) 2010 where a total of 453 rheumatologists from 17 countries have
      participated. The clinical questions concerning pain were formulated and the
      Portuguese group added 2 more questions. A systematic literature search was
      performed in Medline, Embase, Cochrane Library and 2008-2009 EULAR and ACR
      abstracts. The selected articles were systematically reviewed and the evidence
      was defined according to the Oxford Levels of Evidence. In each country a group
      of experts joined to discuss their national recommendations. In Portugal, the
      national meeting was held in October 2010, where 33 rheumatologists discussed and
      voted by Delphi method the national recommendations. Finally, the agreement among
      the rheumatologists and the potential impact on their clinical practice was
      assessed. RESULTS: Thirteen national recommendations were formulated: pain
      measure scores; analgesic combination therapy; pharmacotherapy in preconception,
      pregnancy and lactation periods; pharmacotherapy according to comorbilities;
      safety of NSAIDs and/or paracetamol with methotrexate combination therapy;
      efficacy and safety of continuous/on-demand NSAIDs; opioids, paracetamol,
      corticosteroids, antidepressants, neuromodulators and muscle relaxants role and
      effectiveness; risk factors for the development of chronic pain and the role of
      topic analgesics. CONCLUSION: The portuguese recommendations for the pain
      management by pharmacotherapy in inflammatory arthritis were formulated according
      to the best evidence and supported by a panel of 63 rheumatologists. The
      differences between the national and international recommendations are reported
      in this article.

PMID- 23149640
TI  - [Rheumatic expression of secondary syphilis].
AB  - Syphilis is a disease caused by Treponema pallidum infection with protean
      clinical manifestations. Musculoskeletal complaints are however uncommon and most
      of the time mild. Occasionally they can dominate the clinical picture and
      simulate a variety of rheumatic diseases. The authors present the clinical case
      of a 33-year-old woman who developed a lupus-like syndrome in the postpartum,
      characterized by polyarthritis, elevated acute phase reactants and positive
      antinuclear antibodies (ANA). Physical examination revealed a macular non
      pruriginous skin rash involving the trunk, upper limbs and palms. The Rapid
      Plasma Reagin (RPR) and Treponema Pallidum Hemaglutination (TPHA) tests gave a
      positive result and the patient was diagnosed as secondary syphilis and medicated
      with 2.4 MU of benzathine penicillin intramuscular weekly for 3 weeks, with
      complete resolution of clinical signs and ANA negativation. The association of
      rash and arthritis may occur in several rheumatic diseases but in the presence of
      palmoplantar involvement, the possibility of syphilis infection should not be
      overlooked.

PMID- 23149641
TI  - [Adalimumab induced-inflammatory myopathy in rheumatoid arthritis].
AB  - The application of immunobiologics for the rheumatoid arthritis treatment may
      present as a rare complication the development of inflammatory myopathy. Until
      this moment, there have been described in literature only seven cases of
      inhibitors of tumor necrosis factor induced-myositis. In this paper, we report
      the case of the patient with 39 years-old with eight years of arthritis
      rheumatoid and that due to refractory to various immunosuppressive drugs, the
      adalimumab was introduced, and evolved to dermatomyositis status.

PMID- 23149642
TI  - [Non-traumatic osteonecrosis of the patella, a rare cause of knee pain].
AB  - Non-traumatic osteonecrosis of the patella is a rare cause of knee pain that must
      be present in the diagnostic discussion of disability of the knee with subacute
      character. The author describes a case in which the characteristic images had an
      important role in defining the etiology of disabling knee pain, developing
      pathophysiological hypotheses that may have contributed to the clinical
      presentation, including situations of overuse of the joint.

PMID- 23149643
TI  - Rapid progression of a severe femoral bone loss in a stable revision hip
      prosthesis: causes and management.
AB  - We report a case of a severe bone loss of the proximal femur with a rapid
      progression, in a 72-year-old male patient with a stable total revision hip
      prosthesis. The patient had a persistent mechanical thigh pain. The blood
      laboratory values were normal. Infection disease and osteolytic bone tumor were
      excluded. A surgical procedure was performed. The native bone of the proximal
      femur was resorbed and replaced by a dense fibrous tissue with some sclerotic
      bone fragments. A large amount of a brownish fluid and a red-brown and friable
      tissue were found in the pseudojoint cavity. The proximal femur was reconstructed
      using a large amount of cryopreserved cancellous bone allograft, with retention
      of the femoral prosthesis. The mechanism of the bone lesion can be related not
      only to the host response to the wear particles, but mainly to the fluid pressure
      in the effective joint space. Femoral progressive osteolysis in a stable hip
      prosthesis is an indication for surgery in useful time, before adverse bone
      remodeling can begin and lead to major bone loss.

PMID- 23149644
TI  - Posterior reversible encephalopathy syndrome: the importance of its recognition
      in patients with systemic lupus erythematosus.
AB  - The posterior reversible encephalopathy syndrome (PRES) is a clinical
      radiological entity characterized by the association of clinical neurological
      signs (headache, confusion, vision changes, vomiting and seizures) and the
      typical changes in magnetic resonance imaging of the brain. Its pathogenesis is
      still poorly defined but seems to imply a vascular and endothelial dysfunction.
      It occurs more frequently in patients with hypertensive encephalopathy,
      eclampsia, renal failure and has also been associated with the use of
      immunosuppressive drugs. The authors present a case of PRES in a young woman with
      systemic lupus erythematosus with active and severe manifestations of the
      disease.

PMID- 23149645
TI  - [Gorham-Stout syndrome--a pediatric clinical case].

PMID- 23149646
TI  - Amyloid deposition in rheumatoid arthritis patients.

PMID- 23149647
TI  - Posttraumatic stress disorder and its comorbidities among American Indian
      veterans.
AB  - Goal consists of describing the demographic and comorbid characteristics
      associated with Posttraumatic Stress Disorder (PTSD) among American Indian
      veterans with any lifetime Axis 1 disorder. Sample included 252 American Indian
      veterans, obtained from a community sample of 557, using targeted sampling
      designed to provide a representative sample, structured to include equal numbers
      of rural and urban veterans and a twofold over sample of women. Data collection
      involved lifetime diagnoses based on the Diagnostic Interview Schedule/Quick
      Version/DSM-III-R, demographic characteristics, and combat exposure. Findings
      Bivariate comparisons showed positive relationships of PTSD with combat exposure,
      mood disorder and anxiety disorders (excluding PTSD), but a negative relationship
      with substance use disorder. Binary logistic regression analyses showed an
      independent association of PTSD with mood and anxiety disorders as well as combat
      exposure. 

PMID- 23149648
TI  - Perspectives of people who are deaf and hard of hearing on mental health,
      recovery, and peer support.
AB  - This qualitative study sought to better understand the experiences of deaf and
      hard of hearing individuals with accessing recovery-oriented mental health
      services and peer support via a focus group and interviews. Cultural brokers were
      used to facilitate culturally-sensitive communication with study participants.
      Findings indicate that access to adequate mental health services, not just
      recovery-oriented and peer support services, is not widely available for this
      population, largely due to communication barriers. Feelings of isolation and
      stigma are high among this population. Public mental health systems need to adapt
      and expand services for various cultural groups to insure recovery. 

PMID- 23149649
TI  - The association between breastfeeding, maternal smoking in utero, and birth
      weight with bone mass and fractures in adolescents: a 16-year longitudinal study.
AB  - The aim of this birth cohort study was to determine whether early life factors
      (birth weight, breastfeeding, and maternal smoking) were associated with bone
      mass and fractures in 16-year-old adolescents. The results suggest that
      breastfeeding is associated with higher bone mass and lower fracture risk at age
      16 but not in utero smoking or birth weight. INTRODUCTION: There are limited data
      on early life influences on bone mass in adolescence but we have previously
      reported in utero smoking, breastfeeding, and birth weight were associated with
      bone mass at age 8. METHODS: Birth weight, breastfeeding intention and habit, and
      maternal smoking during pregnancy were assessed at phase one in 1988-1999 and by
      recall during phase two in 1996-1997. Bone mineral density (BMD) was measured by
      dual-energy X-ray densitometry. Fractures were assessed by questionnaire.
      Subjects included 415 male and female adolescents from Southern Tasmania
      representing 29 % of those who originally took part in a birth cohort study in
      1988 and 1989. RESULTS: Breastfeeding (assessed in a number of ways) was
      associated with a 2-3 % increase in BMD at all sites apart from the radius and
      around a one third reduction in fracture risk which persisted after adjustment
      for confounders. In univariate analysis, birth weight was associated with BMD at
      the hip, radius, and total body but this did not persist in multivariate analysis
      and there was no association with fracture. Smoking in utero had no association
      with BMD at any site or fracture. CONCLUSIONS: Breastfeeding is associated with a
      beneficial increase in bone mass at age 16 and a reduction in fracture risk
      during adolescence. The association previously observed at 8 years of age is no
      longer present for birth weight or smoking in utero.

PMID- 23149650
TI  - Inflammatory myofibroblastic tumor of the lung: a rare cause of atelectasis in
      children.
AB  - Although rare, inflammatory myofibroblastic tumor is the most common primary lung
      mass in children. We report the case of an 11-year-old boy investigated for
      persistent cough and dyspnea with complete left lung atelectasis mimicking
      pneumonia. CT and MRI showed an endobronchial mass of the left main bronchus. The
      boy underwent endoscopic resection of the tumor and histology was in favor of an
      inflammatory myofibroblastic tumor of the lung. This diagnosis should be
      suspected in children with recurrent pneumonia. The prognosis is good after
      complete resection.

PMID- 23149651
TI  - Radiologic differences in white matter maturation between preterm and full-term
      infants: TBSS study.
AB  - BACKGROUND: Widespread white matter (WM) pathology in preterm children has been
      proposed. OBJECTIVE: The purpose of this study was to investigate maturational
      differences of WM between preterm infants with thinning of the corpus callosum
      and full-term infants. MATERIALS AND METHODS: A total of 18 preterm children and
      18 full-term children were divided into three subgroups according to the
      corrected age at the time of diffusion tensor imaging scanning. Tract-based
      spatial statistics was used for assessing differences in fractional anisotropy
      (FA) between preterm and full-term children, and between each age-related
      subgroup in preterm and in full-term children. RESULTS: In the preterm group, FA
      values of overall WM showed an increase with age. This trend indicates that WM
      maturation is a gradual occurrence during a child's first 2 years. In the full
      term group, most WM structures had reached maturation at around 1 year of age;
      however, centrum semiovale level showed sustained maturation during the first 2
      years. CONCLUSION: Results of our study demonstrate radiologic maturational
      differences of WM and provide evidence of the need for therapeutic intervention
      within 2 years of birth to prevent specific functional impairment and to improve
      clinical outcome in preterm children.

PMID- 23149652
TI  - Hydrops foetalis with pulmonary hypoplasia in Cheviot and Cheviot-Texel cross
      lambs.

PMID- 23149653
TI  - Physical activity counselling in sports medicine: a call to action.
AB  - Physical activity (PA) is a key component of healthy lifestyle and disease
      prevention. In contrast, physical inactivity accounts for a significant
      proportion of premature deaths worldwide. Physicians are in a critical position
      to help patients develop healthy lifestyles by actively counseling on PA. Sports
      medicine physicians, with their focus on sports and exercise medicine are
      uniquely trained to provide such expertise to patients, learners and colleagues.
      To succeed, physicians need clinical tools and processes that support PA
      assessment and counseling. Linking patients to community resources, and
      specifically to health and fitness professionals is a key strategy. Efforts
      should be made to expand provider education during medical school, residency and
      fellowship training, and continuing medical education. Lastly, physically active
      physicians are more likely to counsel patients to be active. A key message for
      the sports medicine community is the importance of serving as a positive PA role
      model.

PMID- 23149654
TI  - Mass cytometry: protocol for daily tuning and running cell samples on a CyTOF
      mass cytometer.
AB  - In recent years, the rapid analysis of single cells has commonly been performed
      using flow cytometry and fluorescently-labeled antibodies. However, the issue of
      spectral overlap of fluorophore emissions has limited the number of simultaneous
      probes. In contrast, the new CyTOF mass cytometer by DVS Sciences couples a
      liquid single-cell introduction system to an ICP-MS. Rather than fluorophores,
      chelating polymers containing highly-enriched metal isotopes are coupled to
      antibodies or other specific probes. Because of the metal purity and mass
      resolution of the mass cytometer, there is no "spectral overlap" from neighboring
      isotopes, and therefore no need for compensation matrices. Additionally, due to
      the use of lanthanide metals, there is no biological background and therefore no
      equivalent of autofluorescence. With a mass window spanning atomic mass 103-203,
      theoretically up to 100 labels could be distinguished simultaneously. Currently,
      more than 35 channels are available using the chelating reagents available from
      DVS Sciences, allowing unprecedented dissection of the immunological profile of
      samples. Disadvantages to mass cytometry include the strict requirement for a
      separate metal isotope per probe (no equivalent of forward or side scatter), and
      the fact that it is a destructive technique (no possibility of sorting recovery).
      The current configuration of the mass cytometer also has a cell transmission rate
      of only ~25%, thus requiring a higher input number of cells. Optimal daily
      performance of the mass cytometer requires several steps. The basic goal of the
      optimization is to maximize the measured signal intensity of the desired metal
      isotopes (M) while minimizing the formation of oxides (M+16) that will decrease
      the M signal intensity and interfere with any desired signal at M+16. The first
      step is to warm up the machine so a hot, stable ICP plasma has been established.
      Second, the settings for current and make-up gas flow rate must be optimized on a
      daily basis. During sample collection, the maximum cell event rate is limited by
      detector efficiency and processing speed to 1000 cells/sec. However, depending on
      the sample quality, a slower cell event rate (300-500 cells/sec) is usually
      desirable to allow better resolution between cells events and thus maximize
      intact singlets over doublets and debris. Finally, adequate cleaning of the
      machine at the end of the day helps minimize background signal due to free metal.

PMID- 23149655
TI  - Serum alkaline phosphatase, body composition, and risk of metabolic syndrome in
      middle-aged Korean.
AB  - Some papers have suggested that alkaline phosphatase (ALP) level is a predictor
      of the metabolic syndrome (MetS) in the general population. However, the
      association is still controversial, and the mechanisms underlying an association
      between ALP level and the MetS have not been elucidated. We analyzed the
      association between serum ALP level and the development of the MetS over a 4-year
      period. A total of 14,224 subjects who visited the Health Promotion Center for a
      medical examination in 2005 were followed up after 4 years. Serum ALP level
      correlated positively with body fat mass and visceral fat mass. The adjusted
      geometric mean ALP levels were higher in subjects with elevated C-reactive
      protein level or greater fat mass (P < 0.001). None of the subjects had the MetS
      at baseline, but 1,179 exhibited the MetS at the 4-year follow-up. After multiple
      adjustments, the odds ratio (OR) was substantially higher for development of the
      MetS (OR 1.56, 95% confidence intervals, 1.21-2.01) in subjects in the highest
      ALP quintile compared with those in the lowest quintile. After adjusting for
      various covariates, we found significant associations between the quintile of
      serum ALP level and abdominal obesity, low high-density lipoprotein cholesterol
      level, and high triglyceride level. Higher serum ALP level was a significant
      predictor of the MetS in middle-aged Koreans. Serum ALP level correlated
      positively with body fat mass and independently with a more atherogenic lipid
      profile in the general population in Korea.

PMID- 23149657
TI  - Short duration of diabetes and disuse of sulfonylurea have any association with
      insulin cessation of the patients with type 2 diabetes in a clinical setting in
      Japan (JDDM 30).
AB  - Insulin therapy is often required to achieve good glycemic control for the
      patients with type 2 diabetes mellitus (T2DM), while protraction of glycemic
      control without insulin therapy may be preferable for patients. To determine the
      characteristics of and therapeutic regimen in outpatients with T2DM who were able
      to stop insulin therapy with satisfactory glycemic control in a real clinical
      practice setting in Japan by a case-control study. The present study was
      performed on 928 patients with T2DM who started insulin therapy in 2007. Data
      regarding age, sex, body mass index, duration of diabetes, HbA1c, postprandial
      plasma glucose, plasma fasting C-peptide immunoreactivity and treatment modality
      were compared between patients who were able to stop insulin therapy and those
      who continued with insulin. Of the 928 patients, 37 had stopped insulin therapy
      within 1 year. In the patients who stopped insulin therapy, the duration of
      diabetes was significantly shorter and the daily insulin dosage at initiation and
      the prevalence of sulfonylurea pretreatment significantly lower compared with
      patients who continued on insulin. In conclusion, almost 4% of T2DM patients were
      able to stop insulin therapy with satisfactory glycemic control in a real
      clinical practice setting in Japan. Shorter duration of diabetes and disuse of
      sulfonylureas prior to insulin may associate with stopping insulin therapy as a
      near-normoglycemic remission in outpatients with T2DM in Japan.

PMID- 23149658
TI  - Homeostasis model assessment of insulin resistance for evaluating insulin
      sensitivity in patients with type 2 diabetes on insulin therapy.
AB  - Homeostasis model assessment of insulin resistance (HOMA-IR) is a simple and
      useful method for evaluating insulin sensitivity. But it is difficult to apply to
      type2 diabetes patients treated with insulin. We have devised a method for
      measuring HOMA-IR and investigated the validity of HOMA-IR for evaluating insulin
      sensitivity in patients with type 2 diabetes on insulin therapy. In the first arm
      of the study, 19 poorly controlled diabetic subjects were treated with insulin
      and underwent euglycemic clamp study. Then the relationship between insulin
      resistance index assessed by the clamp test (clamp-IR) and HOMA-IR was
      investigated in these subjects. Log transformed HOMA-IR correlated with log
      transformed M/I values derived from the standard euglycemic clamp (r=-0.753,
      p=0.002). In the second arm of the study, we investigated the relationship
      between HOMA-IR and various clinical parameters in 156 patients with poorly
      controlled diabetes after glycemic control. Log transformed HOMA-IR correlated
      negatively with age (r=-0.292, p=0.0002), HDL-C (r=-0.342, p<0.0001), log
      transformed serum adiponectin (r=-0.309, p=0.0006) and log transformed KITT (r=
      0.264, p=0.0009), and positively with body mass index (r=0.499, p<0.0001), waist
      circumstance (r=0.461, p<0.0001), visceral fat area (r=0.401, p<0.0001),
      diastolic blood pressure (r=0.223, p=0.0054), log transformed triglyceride
      (r=0.497, p<0.0001), urinary CPR (r=0.216, p=0.0099), DeltaCPR of glucagon
      stimulation test (r=0.496, p<0.0001) and log transformed insulinogenic index
      (r=0.325, p=0.0002). These results suggest that HOMA-IR is a useful test for the
      evaluation of insulin sensitivity even in patients with type 2 diabetes treated
      with insulin.

PMID- 23149659
TI  - Direct effects of IL-4 on mast cells drive their intestinal expansion and
      increase susceptibility to anaphylaxis in a murine model of food allergy.
AB  - Interleukin (IL)-4 has critical roles in allergic disorders, including food
      hypersensitivity. The direct effects of the cytokine on the survival and function
      of mast cells, the key effectors of food anaphylaxis, have not been established.
      In this study, we demonstrate that IL-4 induces a marked intestinal mastocytosis
      in mice. This phenotype is reproduced in animals expressing Il4ralphaF709, an
      activating variant of the IL-4 receptor alpha-chain (IL-4Ralpha). Il4ralphaF709
      mice exhibit enhanced anaphylactic reactions but unaltered physiological
      responses to vasoactive mediators. IL-4 induces Bcl-2 and Bcl-X(L) and enhances
      survival and stimulates proliferation in cultured bone marrow-derived mast cells
      (BMMC). These effects are STAT6 (signal transducer and activator of transcription
      factor 6)-dependent and are amplified in Il4ralphaF709 BMMC. In competitive bone
      marrow chimeras, Il4ralphaF709 mast cells display a substantial competitive
      advantage over wild-type mast cells, which, in turn, prevail over IL-4Ralpha-/-
      mast cells in populating the intestine, establishing a cell-intrinsic effect of
      IL-4 in intestinal mast cell homeostasis. Our results demonstrate that IL-4
      signaling is a key determinant of mast cell expansion in food allergy.

PMID- 23149660
TI  - Host-dependent control of early regulatory and effector T-cell differentiation
      underlies the genetic susceptibility of RAG2-deficient mouse strains to transfer
      colitis.
AB  - De novo differentiation of CD4(+)Foxp3(+) regulatory T cells (induced (i) Tregs)
      occurs preferentially in the gut-associated lymphoid tissues (GALT). We addressed
      the contribution of background genetic factors in affecting the balance of iTreg,
      T helper type 1 (Th1), and Th17 cell differentiation in GALT in vivo following
      the transfer of naive CD4(+)CD45RB(high) T cells to strains of RAG2-deficient
      mice with differential susceptibility to inflammatory colitis. iTregs represented
      up to 5% of CD4(+) T cells in mesenteric lymph nodes of less-susceptible C57BL/6
      RAG2(-/-) mice compared with <1% in highly susceptible C57BL/10 RAG2(-/-) mice 2
      weeks following T-cell transfer before the onset of colitis. Early Treg induction
      was correlated inversely with effector cell expansion and the severity of colitis
      development, was controlled primarily by host and not T-cell-dependent factors,
      and was strongly associated with interleukin-12 (IL-12)/23 production by host
      CD11c(+)CD103(+) dendritic cells. These data highlight the importance of genetic
      factors regulating IL-12/23 production in controlling the balance between iTreg
      differentiation and effector-pathogenic CD4(+) T-cell expansion in lymphopenic
      mice and indicate a direct role for iTregs in the regulation of colonic
      inflammation in vivo.

PMID- 23149661
TI  - Preferential depletion of gut CD4-expressing iNKT cells contributes to systemic
      immune activation in HIV-1 infection.
AB  - Chronic inappropriate immune activation is the central defect-driving loss of
      CD4(+) T helper cells and progression to AIDS in persons with HIV-1 infection,
      but the mechanisms remain controversial. We examined key regulatory invariant
      receptor natural killer T (iNKT) cells in the gut, the largest reservoir of
      lymphocytes and a key arena of HIV-1 pathogenesis. In healthy control persons,
      the anti-inflammatory CD4(+) iNKT-cell subset predominated over the pro
      inflammatory CD4(-) iNKT-cell subset in the gut, but not in the blood,
      compartment. HIV-1 infection resulted in a preferential loss of this anti
      inflammatory CD4(+) iNKT-cell subset within the gut. The degree of loss of the
      CD4(+) iNKT-cell subset in the gut, but not in the blood, correlated to the
      systemic immune activation and exhaustion that have been linked to disease
      progression. These results suggest a potentially important contribution of gut
      iNKT-cell imbalance in determining the systemic immune activation that is the
      hallmark of HIV-1 pathogenesis.

PMID- 23149663
TI  - MUC1 and MUC13 differentially regulate epithelial inflammation in response to
      inflammatory and infectious stimuli.
AB  - The MUC1 cell-surface mucin is highly expressed on the gastric mucosal surface,
      while MUC13 is highly expressed on the intestinal mucosal surface. Polymorphisms
      in both MUC1 and MUC13 have been linked to inflammatory bowel diseases. MUC1 can
      act as a decoy molecule on the apical cell surface of epithelial cells and
      thereby limit bacterial adherence, infection, and inflammation. In this study, we
      examined whether and how MUC1 and MUC13 modulate infectious and inflammatory
      signaling. Using gastrointestinal tissue from Muc1- or Muc13-deficient mice in ex
      vivo culture, MUC1 small interfering RNA (siRNA) silencing in MKN7 gastric
      epithelial cells, and MUC13 siRNA silencing in LS513 intestinal epithelial cells,
      we showed that loss of MUC1 increased chemokine secretion, whereas loss of MUC13
      decreased chemokine secretion in response to tumor necrosis factor-alpha. Anti
      inflammatory activity of MUC1 and pro-inflammatory activity of MUC13 were also
      seen after exposure to pathogens, NOD1 (nucleotide-binding oligomerisation domain
      containing protein-1), and Toll-like receptor ligands. MUC1 and MUC13 both
      regulate chemokine secretion in gastrointestinal epithelial cells through a
      nuclear factor-kappaB-dependent pathway, although MUC13 modulation could also
      involve other pathways. Our studies demonstrate that MUC1 and MUC13 are important
      components of gastrointestinal homeostasis and that disruption or inappropriate
      expression of these mucins could predispose to infectious and inflammatory
      disease and inflammation-induced cancer.

PMID- 23149664
TI  - Antenatal ureaplasma infection impairs development of the fetal ovine gut in an
      IL-1-dependent manner.
AB  - Ureaplasma infection of the amniotic cavity is associated with adverse postnatal
      intestinal outcomes. We tested whether interleukin-1 (IL-1) signaling underlies
      intestinal pathology following ureaplasma exposure in fetal sheep. Pregnant ewes
      received intra-amniotic injections of ureaplasma or culture media for controls at
      3, 7, and 14 d before preterm delivery at 124 d gestation (term 150 d). Intra
      amniotic injections of recombinant human interleukin IL-1 receptor antagonist
      (rhIL-1ra) or saline for controls were given 3 h before and every 2 d after
      Ureaplasma injection. Ureaplasma exposure caused fetal gut inflammation within 7
      d with damaged villus epithelium and gut barrier loss. Proliferation,
      differentiation, and maturation of enterocytes were significantly reduced after 7
      d of ureaplasma exposure, leading to severe villus atrophy at 14 d. Inflammation,
      impaired development and villus atrophy of the fetal gut was largely prevented by
      intra-uterine rhIL-1ra treatment. These data form the basis for a clinical
      understanding of the role of ureaplasma in postnatal intestinal pathologies.

PMID- 23149662
TI  - PD-L2 modulates asthma severity by directly decreasing dendritic cell IL-12
      production.
AB  - Studies examining the role of programmed death 1 (PD-1) ligand 2 (PD-L2)/PD-1 in
      asthma have yielded conflicting results. To clarify its role, we examined the PD
      L2 expression in biopsies from human asthmatics and the lungs of aeroallergen
      treated mice. PD-L2 expression in bronchial biopsies correlated with the severity
      of asthma. In mice, allergen exposure increased PD-L2 expression on pulmonary
      myeloid dendritic cells (DCs), and PD-L2 blockade diminished allergen-induced
      airway hyperresponsiveness (AHR). By contrast, PD-1 blockade had no impact,
      suggesting that PD-L2 promotes AHR in a PD-1-independent manner. Decreased AHR
      was associated with enhanced serum interleukin (IL)-12 p40, and in vitro
      stimulation of DCs with allergen and PD-L2-Fc reduced IL-12 p70 production,
      suggesting that PD-L2 inhibits allergen-driven IL-12 production. In our model, IL
      12 did not diminish T helper type 2 responses but rather directly antagonized IL
      13-inducible gene expression, highlighting a novel role for IL-12 in regulation
      of IL-13 signaling. Thus, allergen-driven enhancement of PD-L2 signaling through
      a PD-1-independent mechanism limits IL-12 secretion, exacerbating AHR.

PMID- 23149665
TI  - TIM-4, expressed by medullary macrophages, regulates respiratory tolerance by
      mediating phagocytosis of antigen-specific T cells.
AB  - Respiratory exposure to antigen induces T cell tolerance via several overlapping
      mechanisms that limit the immune response. While the mechanisms involved in the
      development of Treg cells have received much attention, those that result in T
      cell deletion are largely unknown. Herein, we show that F4/80(+) lymph node
      medullary macrophages expressing TIM-4, a phosphatidylserine receptor, remove
      antigen-specific T cells during respiratory tolerance, thereby reducing secondary
      T cell responses. Blockade of TIM-4 inhibited the phagocytosis of antigen
      specific T cells by TIM-4 expressing lymph node medullary macrophages, resulting
      in an increase in the number of antigen-specific T cells and the abrogation of
      respiratory tolerance. Moreover, specific depletion of medullary macrophages
      inhibited the induction of respiratory tolerance, highlighting the key role of
      TIM-4 and medullary macrophages in tolerance. Therefore, TIM-4-mediated clearance
      of antigen specific T cells represents an important previously unrecognized
      mechanism regulating respiratory tolerance.

PMID- 23149666
TI  - The C-C motif chemokine ligands CCL5, CCL11, and CCL24 induce the migration of
      circulating fibrocytes from patients with severe asthma.
AB  - The C-C motif chemokine ligand 5 (CCL5), CCL11, and CCL24 are involved in the
      pathogenesis of asthma, and their function is mainly associated with the airway
      recruitment of eosinophils. This study tested their ability to induce the
      migration of circulating fibrocytes, which may contribute to the development of
      irreversible airflow obstruction in severe asthma. The sputum fluid phase (SFP)
      from patients with severe/treatment-refractory asthma (PwSA) contained elevated
      concentrations of CCL5, CCL11, and CCL24 in comparison with the SFP from patients
      with non-severe/treatment-responsive asthma (PwNSA). The circulating fibrocytes
      from PwSA expressed the receptors for these chemokines at increased levels and
      migrated in response to recombinant CCL5, CCL11, and CCL24. The SFP from PwSA
      induced the migration of autologous fibrocytes, and its activity was
      significantly attenuated by neutralization of endogenous CCL5, CCL11, and CCL24.
      These findings suggest that CCL5, CCL11, and CCL24 may contribute to the airway
      recruitment of fibrocytes in severe asthma.

PMID- 23149668
TI  - Attenuating endoplasmic reticulum stress as a novel therapeutic strategy in
      pulmonary hypertension.
AB  - BACKGROUND: Evidence suggestive of endoplasmic reticulum (ER) stress in the
      pulmonary arteries of patients with pulmonary arterial hypertension has been
      described for decades but has never been therapeutically targeted. ER stress is a
      feature of many conditions associated with pulmonary arterial hypertension like
      hypoxia, inflammation, or loss-of-function mutations. ER stress signaling in the
      pulmonary circulation involves the activation of activating transcription factor
      6, which, via induction of the reticulin protein Nogo, can lead to the disruption
      of the functional ER-mitochondria unit and the increasingly recognized cancer
      like metabolic shift in pulmonary arterial hypertension that promotes
      proliferation and apoptosis resistance in the pulmonary artery wall. We
      hypothesized that chemical chaperones known to suppress ER stress signaling, like
      4-phenylbutyrate (PBA) or tauroursodeoxycholic acid, will inhibit the disruption
      of the ER-mitochondrial unit and prevent/reverse pulmonary arterial hypertension.
      METHODS AND RESULTS: PBA in the drinking water both prevented and reversed
      chronic hypoxia-induced pulmonary hypertension in mice, decreasing pulmonary
      vascular resistance, pulmonary artery remodeling, and right ventricular
      hypertrophy and improving functional capacity without affecting systemic
      hemodynamics. These results were replicated in the monocrotaline rat model. PBA
      and tauroursodeoxycholic acid improved ER stress indexes in vivo and in vitro,
      decreased activating transcription factor 6 activation (cleavage, nuclear
      localization, luciferase, and downstream target expression), and inhibited the
      hypoxia-induced decrease in mitochondrial calcium and mitochondrial function. In
      addition, these chemical chaperones suppressed proliferation and induced
      apoptosis in pulmonary artery smooth muscle cells in vitro and in vivo.
      CONCLUSIONS: Attenuating ER stress with clinically used chemical chaperones may
      be a novel therapeutic strategy in pulmonary hypertension with high translational
      potential.

PMID- 23149669
TI  - Timing, predictive factors, and prognostic value of cerebrovascular events in a
      large cohort of patients undergoing transcatheter aortic valve implantation.
AB  - BACKGROUND: The objective of this study was to evaluate the timing, predictive
      factors, and prognostic value of cerebrovascular events (CVEs) after
      transcatheter aortic valve implantation. METHODS AND RESULTS: The study included
      1061 consecutive patients who underwent transcatheter aortic valve implantation
      with a balloon-expandable (64%) or self-expandable (36%) valve. CVEs were
      classified as acute (<=24 hours), subacute (1-30 days), or late (>30 days). CVEs
      occurred in 54 patients (5.1%; stroke, 4.2%) within 30 days after transcatheter
      aortic valve implantation (acute in 54% of cases). The predictors of acute CVEs
      were balloon postdilation of the valve prosthesis (odds ratio, 2.46; 95%
      confidence interval,1.07-5.67) and valve dislodgment/embolization (odds ratio,
      4.36; 95% CI, 1.21-15.69); new-onset atrial fibrillation (odds ratio, 2.76; 95%
      CI, 1.11-6.83) was a predictor of subacute CVEs. Late CVEs occurred in 35
      patients (3.3%; stroke, 2.1%) at a median follow-up of 12 months (3-23 months).
      The predictors of late CVEs were chronic atrial fibrillation (2.84; 95% CI, 1.46
      5.53), peripheral vascular disease (hazard ratio, 2.02; 95% CI, 1.02-3.97), and
      prior cerebrovascular disease (hazard ratio, 2.04; 95% CI, 1.01-4.15). Major
      stroke was associated with 30-day (odds ratio, 7.43; 95% CI, 2.45-22.53) and late
      (hazard ratio, 1.75; 95% CI, 1.01-3.04) mortality. CONCLUSIONS: In a large cohort
      of patients undergoing transcatheter aortic valve implantation, the rates of
      acute and subacute CVEs were 2.7% and 2.4%, respectively. While balloon
      postdilation and valve dislodgment/embolization were the predictors of acute
      CVEs, new-onset atrial fibrillation determined a higher risk for subacute events.
      Late events were determined mainly by a history of chronic atrial fibrillation
      and peripheral and cerebrovascular disease. The occurrence of major stroke was
      associated with increased early and late mortality. These results provide
      important insights for the implementation of preventive measures for CVEs after
      transcatheter aortic valve implantation.

PMID- 23149670
TI  - Retinal pigment epithelium folds as a diagnostic finding of Vogt-Koyanagi-Harada
      disease.
AB  - OBJECTIVE: To examine using the folds of the retinal pigment epithelium (RPE) to
      diagnose Vogt-Koyanagi-Harada (VKH) disease. METHODS: Retrospective clinical
      review of 57 Japanese patients between July 2005 and April 2009. Optical
      coherence tomography (OCT), fundus photographs and fluorescein angiography (FA)
      were studied to investigate Kendall's coefficients of concordance in seven
      findings by four ophthalmologists. The sensitivity and specificity of each
      finding were examined to confirm its efficacy. Each result was defined as
      positive when more than three of the ophthalmologists judged that the finding
      existed. RESULTS: The folds of the RPE on OCT were observed in 30/42 (71.4 %)
      eyes having VKH disease, but none in the other 72 eyes. Kendall's coefficient of
      concordance in the detection of the folds of the RPE was 0.90 and was the highest
      among all other findings. Sensitivity was higher in the detection of the RPE
      folds on OCT and in optic nerve staining on FA than other findings and the
      specificity was 100 % for the RPE folds and 26.7 % for the optic nerve staining.
      CONCLUSION: The detection of the folds of the RPE on OCT is a simple and
      effective method to help diagnose VKH disease at its acute stage which does not
      require pupil dilation.

PMID- 23149671
TI  - Isoenzyme and ultrastructural characterization of Leishmania tropica axenic
      amastigotes and promastigotes.
AB  - Leishmania tropica is one of the main etiological agents of cutaneous
      leishmaniasis in Iran. For ultrastructural and isoenzyme study, axenic
      amastigotes were cultured in a brain-heart infusion medium containing 20 % fetal
      calf serum, pH 4.5, and incubated at 37  degrees C in 5 % CO(2). Different stages
      of L. tropica revealed the same isoenzyme profiles after comparing four enzyme
      systems including phosphoglucomutase, 6-phosphogluconate dehydrogenase, malate
      dehydrogenase, and nucleoside hydrolase II. Different isoenzyme patterns for
      glucose-phosphate isomerase, glucose-6-phosphate dehydrogenase, nucleoside
      hydrolase I, and malic enzyme enzymic systems were seen; thus, these isoenzyme
      systems among the eight systems studied were more efficient in characterizing L.
      tropica amastigotes. The structure of the axenic amastigotes was essentially
      similar to that of the promastigotes except for some important characteristics
      including the flagellum, flagellar pocket, paraxial rod, and the subpellicular
      microtubules.

PMID- 23149672
TI  - Socio-ethical education in nanotechnology engineering programmes: a case study in
      Malaysia.
AB  - The unique properties of nanotechnology have made nanotechnology education and
      its related subjects increasingly important not only for students but for mankind
      at large. This particular technology brings educators to work together to prepare
      and produce competent engineers and scientists for this field. One of the key
      challenges in nanotechnology engineering is to produce graduate students who are
      not only competent in technical knowledge but possess the necessary attitude and
      awareness toward the social and ethical issues related to nanotechnology. In this
      paper, a research model has been developed to assess Malaysian nanotechnology
      engineering students' attitudes and whether their perspectives have attained the
      necessary objectives of ethical education throughout their programme of study.
      The findings from this investigation show that socio ethical education has a
      strong influence on the students' knowledge, skills and attitudes pertaining to
      socio ethical issues related to nanotechnology.

PMID- 23149673
TI  - High quality gold nanorods and nanospheres for surface-enhanced Raman scattering
      detection of 2,4-dichlorophenoxyacetic acid.
AB  - Nearly monodisperse Au nanorods (NRs) with different aspect ratios were separated
      from home-synthesized polydisperse samples using a gradient centrifugation
      method. The morphology, size and its distribution, and photo-absorption property
      were analyzed by transmission electron microscopy, atomic force microscopy and UV
      visible spectroscopy. Subsequently, using colloidal Au NRs (36.2 nm *10.7 nm)
      with 97.4% yield after centrifugation and Au nanospheres (NSs) (22.9 +/- 1.0 nm
      in diameter) with 97.6% yield as Au substrates, surface-enhanced Raman scattering
      (SERS) spectra of 2,4-dichlorophenoxyacetic acid (2,4-D) were recorded using
      laser excitation at 632.8 nm. Results show that surface enhancement factors (EF)
      for Au NRs and NSs are 6.2 * 10(5) and 5.7 * 10(4) using 1.0 * 10(-6) M 2,4-D,
      respectively, illustrating that EF value is a factor of ~10 greater for Au NRs
      substrates than for Au NSs substrates. As a result, large EF are a mainly result
      of chemical enhancement mechanisms. Thus, it is expected that Au NPs can find a
      comprehensive SERS application in the trace detection of pesticide residues.

PMID- 23149674
TI  - Combination between [B-alpha-SiW9O34] unit and triangular inorganic Ni6 core
      under hydrothermal conditions: from monomer to rare dimer with malposed dodeca
      nickel centers.
AB  - The hydrothermal reactions of alpha-K(4)SiW(12)O(40) with NiCl(2).6H(2)O yielded
      two unprecedented silicotungstates containing a triangular inorganic Ni(6) core.
      Furthermore, Na(2)[Ni(6)(MU(3)-OH)(3)(H(2)O)(9)SiW(9)O(34)](2).17H(2)O (1)
      presents a rare dimer, in which two SiW(9) units sandwich double Ni(6) cores by W
      O-Ni linking instead of conventional Ni-O-Ni.

PMID- 23149675
TI  - An in situ polymerization approach for the synthesis of superhydrophobic and
      superoleophilic nanofibrous membranes for oil-water separation.
AB  - Superhydrophobic and superoleophilic nanofibrous membranes exhibiting robust oil
      water separation performance were prepared by a facile combination of electrospun
      cellulose acetate (CA) nanofibers and a novel in situ polymerized fluorinated
      polybenzoxazine (F-PBZ) functional layer that incorporated silica nanoparticles
      (SiO(2) NPs). By employing the F-PBZ/SiO(2) NPs modification, the pristine
      hydrophilic CA nanofibrous membranes were endowed with a superhydrophobicity with
      the water contact angle of 161 degrees  and a superoleophilicity with the oil
      contact angle of 3 degrees . Surface morphological studies have indicated that
      the wettability of resultant membranes could be manipulated by tuning the surface
      composition as well as the hierarchical structures. The quantitative hierarchical
      roughness analysis using the N(2) adsorption method has confirmed the major
      contribution of SiO(2) NPs on enhancing the porous structure, and a detailed
      correlation between roughness and solid-liquid interface pinning is proposed.
      Furthermore, the as-prepared membranes exhibited fast and efficient separation
      for oil-water mixtures and excellent stability over a wide range of pH
      conditions, which would make them a good candidate in industrial oil-polluted
      water treatments and oil spill cleanup, and also provided a new insight into the
      design and development of functional nanofibrous membranes through F-PBZ
      modification.

PMID- 23149676
TI  - Stress response pathways, toxicity pathways and adverse outcome pathways.

PMID- 23149677
TI  - The fate and role of bone graft-derived cells after autologous tendon and bone
      transplantation into the bone tunnel.
AB  - BACKGROUND: Grafting bone between the tendon graft and the bone tunnel in
      anterior cruciate ligament reconstruction increases the mechanical strength of
      the tendon graft. However, the biological role of the bone graft is unclear. The
      purpose of this research was to elucidate the role of bone graft cells after
      autologous tendon graft into the bone tunnel with an autologous bone graft in
      green fluorescent protein (GFP) transgenic rats. METHODS: The Achilles tendons of
      Sprague-Dawley (SD) wild-type rats and bone of GFP rats were harvested and
      transplanted into bone tunnels drilled in the femurs at the knees of SD rats. The
      femurs were harvested at 1, 2, and 4 weeks after transplantation and
      histologically investigated using hematoxylin and eosin staining and
      immunostaining of heat shock protein 47 (HSP47), macrophages, and type I and type
      III collagens. Biomechanical tests were performed on the tendon graft 2 and 4
      weeks after transplantation to evaluate the ultimate force to failure. RESULTS: A
      small number of GFP-positive cells was seen in the tendon graft 2 weeks after
      transplantation. The cell count in the tendon graft was increased at 4 weeks
      after transplantation. HSP47-positive cells and macrophage-stained cells present
      in the tendon graft corresponded with the GFP-positive cells. By 2 weeks after
      transplantation, the relative areas of immunostained type I and III collagens in
      the tendon graft had declined significantly in the bone graft group compared to
      the control. The ultimate failure load in the bone graft group was higher than
      that in the control group at both 2 and 4 weeks after transplantation.
      CONCLUSIONS: This research showed that, within 4 weeks of transplantation, bone
      graft cells migrate to the tendon graft, where they differentiate into cells
      involved in collagen production and macrophages. Bone graft cells may contribute
      to the early stage remodeling of tendon grafts.

PMID- 23149679
TI  - Identification of gntK, a gene required for the methylation of purpurosamine C-6'
      in gentamicin biosynthesis.
AB  - Gentamicin and sisomicin are two different aminoglycoside antibiotics. The
      comparison of their chemical structure and biosynthetic gene clusters, coupled
      with bioinformatic analysis, suggested that the gntK gene would be associated
      with methylation. The gntK gene fragment in M. purpurea G1008 was inactivated by
      genetic engineering and its mutant strain M. purpurea GK1101 (DeltagntK) was
      screened. The metabolites of G1008 and GK1101 was analyzed by HPLC-MS, which
      revealed that GK1101 no longer produced gentamicin C(1) or C(2), while mainly
      synthesizing gentamicin C(1a), and the production of C(1a) increased
      significantly. This indicated that the metabolic flow for the gentamicin C(1) and
      C(2) biosynthesis was blocked by disrupting the gntK gene, which substantiated
      that the gntK gene encoded the enzyme that catalyzes the methylation of
      purpurosamine C-6'. The mutant GK1101 has good prospects for industrial
      application. In addition, our study provides information that can be used to
      clarify the function of a single gene and simplify the targeted genetic breeding
      of important pharmaceutical microorganisms.

PMID- 23149678
TI  - Toxic effects, uptake, and translocation of Cd and Pb in perennial ryegrass.
AB  - Cadmium (Cd) and lead (Pb) are regarded as the most toxic environmental
      pollutants because they are a threat not only to plants, but also to humans.
      Better understanding of the growth response, uptake and translocation of Cd and
      Pb in perennial ryegrass (Lolium perenne L.) would be helpful to evaluate the
      role of this grass species as a potential candidate used for phyto-remediation.
      Perennial ryegrass seedlings were subjected to three Pb levels (0, 0.5, and 3.2
      mM) for 6 days and three Cd levels (0, 0.2, and 0.5 mM) for 7 days in a walk-in
      growth room. The Cd and Pb reduced the normalized transpiration and growth rate.
      Greater amount of Cd and Pb accumulated in roots relative to shoots. The
      enrichment coefficient (EC) and translocation factor (TF) were greater in plants
      treated with Cd than those with Pb. The dose of Cd had no effect on EC and TF.
      However, the plants subjected to higher dose of Pb had a greater TF and a lower
      EC relative to that with lower dose of Pb. Meanwhile, removal rates were
      decreased when the doses of Pb and Cd increased. The results indicated that
      perennial ryegrass preferred Cd assimilation to Pb, and can be considered as one
      of the plant species which accumulate high levels of Cd and Pb.

PMID- 23149680
TI  - Novosphingobium sediminis sp. nov., isolated from the sediment of a eutrophic
      lake.
AB  - A Gram-negative, rod-shaped, aerobic, non-motile, bacterium (YG-17(T)) was
      isolated from eutrophic Taihu lake sediment. Colonies grown on YG agar plates
      were circular, convex, and yellow-colored. On the basis of 16S rRNA gene sequence
      similarity, strain YG-17(T) was shown to be closely related to Novosphingobium
      aromaticivorum (97.9%), followed by Novosphingobium stygium (97.5%),
      Novosphingobium subterranea (96.9%) and Novosphingobium taihuense (96.7%). The
      DNA-DNA relatedness values of strain YG-17(T) to the most phylogenetically
      related species N. aromaticivorum and N. stygium were 14% and 21%, respectively.
      The G+C content of the genomic DNA was 63.2 mol%. The major respiratory quinone
      was ubiquinone-10 and major fatty acids were C(18:1 omega7c), C(17:1 omega6c) and
      C(14:0)2-OH. Sphingoglycolipids were present, and spermidine was detected as the
      major polyamine. According to comparative physiological and chemotaxonomic
      analysis, strain YG-17(T) is proposed to be a novel species of the genus
      Novosphingobium, with the name of Novosphingobium sediminis sp. nov. The type
      strain is YG-17(T) (NBRC 106119(T)= CGMCC 1.9114(T)).

PMID- 23149681
TI  - Genome-wide survey of polyketide synthase and nonribosomal peptide synthetase
      gene clusters in Streptomyces turgidiscabies NBRC 16081.
AB  - Although members of the genus Streptomyces are useful producers of secondary
      metabolites, Streptomyces turgidiscabies, a cause of potato scab, has not been
      investigated for this purpose. To examine the potential of S. turgidiscabies as a
      secondary metabolite producer, its polyketide synthase (PKS) and nonribosomal
      peptide synthetase (NRPS) gene clusters, conferring major biosynthetic pathways
      in actinomycetes, were surveyed using whole genome analysis of S. turgidiscabies
      NBRC 16081. This strain possessed seventeen PKS and NRPS gene clusters composed
      of two type-I PKS, two type-II PKS, seven NRPS, and six PKS/NRPS hybrid clusters.
      Abundance of these gene clusters was not only comparable to those of industrially
      useful strains such as S. avermitilis MA-4680 and S. griseus subsp. griseus NBRC
      13350, but also superior to those of genetically well-studied S. coelicolor A3(2)
      and potato scab-causing S. scabiei 87.22. Remarkably, its PKS/NRPS gene clusters
      were more diverse in their module organization than those of other Streptomyces
      strains, although it possessed the lowest number of type-I PKS gene clusters. Our
      results suggest that S. turgidiscabies, unlike S. scabiei, harbors considerable
      genetic potential for producing diverse polyketide and peptide compounds.

PMID- 23149682
TI  - Citricoccus yambaruensis sp. nov., a racemic phenylsuccinate stereospecifically
      assimilating actinomycete isolated from soil in Okinawa.
AB  - A bacterial strain, designated PS9(T), was isolated from soil in the Ryukyu
      Archipelago, Japan. The bacterium grew with racemic phenylsuccinate as the sole
      carbon and energy source. Phylogenetic analysis based on the 16S rRNA gene
      sequence showed that strain PS9(T) was closely related to Citricoccus muralis, C.
      alkalitolerans and C. nitrophenolicus with sequence similarities of 97.5, 97.8,
      and 98.3%, respectively, suggesting that the strain belonged to the genus
      Citricoccus. Strain PS9(T) was a Gram-positive, non-motile, circular-shaped and
      aerobic bacterium. The major respiratory quinone was MK-8 (H(2)) and the
      predominant cellular fatty acid was C(15:0) anteiso, C(17:0) anteiso, and C(15:0)
      iso. The G+C content was 72.4 mol%. Based on the phylogenetic and phenotypic
      traits, it was concluded that the organism represents a new species in the genus
      Citricoccus, with the name Citricoccus yambaruensis. The type strain is PS9(T)
      (=NBRC102121(T) = DSM18783(T)).

PMID- 23149683
TI  - Spongitalea numazuensis gen. nov., sp. nov., a new marine bacterium of the family
      Flavobacteriaceae isolated from an unidentified marine sponge.
AB  - Polyphasic taxonomic investigation was conducted on a strictly aerobic, Gram
      negative, non-motile, pale-yellow-pigmented, rod-shaped strain designated HJ24(T)
      which was isolated from an unidentified orange-colored marine sponge.
      Phylogenetic analysis based on the 16S rRNA gene sequence revealed that the novel
      isolate could be affiliated with the family Flavobacteriaceae of the phylum
      Bacteroidetes and that it showed highest sequence similarity (88.6%) with
      Pseudozobellia thermophila KMM 3531(T). The novel isolate is phenotypically and
      physiologically different from other related genera. The DNA G+C contents were 41
      mol%, MK-6 was the major menaquinone and iso-C15:0, iso-C15:1 and iso-C17:0 3-OH
      were the predominant fatty acids. On the basis of polyphasic taxonomic studies,
      it was concluded that the novel strain represents a new genus and a novel species
      of the family Flavobacteriaceae. We propose the name Spongitalea numazuensis gen.
      nov., sp. nov. for this strain; its type strain is HJ24(T) (= DSM 21243(T)).

PMID- 23149684
TI  - An examination of an Antarctic soil metagenomic-derivate putative
      methylthioadenosine phosphorylase gene as a novel reporter gene for promoter
      trapping.

PMID- 23149685
TI  - Description of Komagataeibacter gen. nov., with proposals of new combinations
      (Acetobacteraceae).

PMID- 23149686
TI  - Competition between species can stabilize public-goods cooperation within a
      species.
AB  - Competition between species is a major ecological force that can drive evolution.
      Here, we test the effect of this force on the evolution of cooperation within a
      species. We use sucrose metabolism of budding yeast, Saccharomyces cerevisiae, as
      a model cooperative system that is subject to social parasitism by cheater
      strategies. We find that when cocultured with a bacterial competitor, Escherichia
      coli, the frequency of cooperator phenotypes in yeast populations increases
      dramatically as compared with isolated yeast populations. Bacterial competition
      stabilizes cooperation within yeast by limiting the yeast population density and
      also by depleting the public goods produced by cooperating yeast cells. Both of
      these changes induced by bacterial competition increase the cooperator frequency
      because cooperator yeast cells have a small preferential access to the public
      goods they produce; this preferential access becomes more important when the
      public good is scarce. Our results indicate that a thorough understanding of
      species interactions is crucial for explaining the maintenance and evolution of
      cooperation in nature.

PMID- 23149688
TI  - Regulation of yeast central metabolism by enzyme phosphorylation.
AB  - As a frequent post-translational modification, protein phosphorylation regulates
      many cellular processes. Although several hundred phosphorylation sites have been
      mapped to metabolic enzymes in Saccharomyces cerevisiae, functionality was
      demonstrated for few of them. Here, we describe a novel approach to identify in
      vivo functionality of enzyme phosphorylation by combining flux analysis with
      proteomics and phosphoproteomics. Focusing on the network of 204 enzymes that
      constitute the yeast central carbon and amino-acid metabolism, we combined
      protein and phosphoprotein levels to identify 35 enzymes that change their degree
      of phosphorylation during growth under five conditions. Correlations between
      previously determined intracellular fluxes and phosphoprotein abundances provided
      first functional evidence for five novel phosphoregulated enzymes in this
      network, adding to nine known phosphoenzymes. For the pyruvate dehydrogenase
      complex E1 alpha subunit Pda1 and the newly identified phosphoregulated glycerol
      3-phosphate dehydrogenase Gpd1 and phosphofructose-1-kinase complex beta subunit
      Pfk2, we then validated functionality of specific phosphosites through absolute
      peptide quantification by targeted mass spectrometry, metabolomics and
      physiological flux analysis in mutants with genetically removed phosphosites.
      These results demonstrate the role of phosphorylation in controlling the
      metabolic flux realised by these three enzymes.

PMID- 23149687
TI  - Modelling reveals novel roles of two parallel signalling pathways and homeostatic
      feedbacks in yeast.
AB  - The high osmolarity glycerol (HOG) pathway in yeast serves as a prototype
      signalling system for eukaryotes. We used an unprecedented amount of data to
      parameterise 192 models capturing different hypotheses about molecular mechanisms
      underlying osmo-adaptation and selected a best approximating model. This model
      implied novel mechanisms regulating osmo-adaptation in yeast. The model suggested
      that (i) the main mechanism for osmo-adaptation is a fast and transient non
      transcriptional Hog1-mediated activation of glycerol production, (ii) the
      transcriptional response serves to maintain an increased steady-state glycerol
      production with low steady-state Hog1 activity, and (iii) fast negative feedbacks
      of activated Hog1 on upstream signalling branches serves to stabilise adaptation
      response. The best approximating model also indicated that homoeostatic adaptive
      systems with two parallel redundant signalling branches show a more robust and
      faster response than single-branch systems. We corroborated this notion to a
      large extent by dedicated measurements of volume recovery in single cells. Our
      study also demonstrates that systematically testing a model ensemble against data
      has the potential to achieve a better and unbiased understanding of molecular
      mechanisms.

PMID- 23149691
TI  - Screening for injurious falls in acute care hospitals.
AB  - BACKGROUND: Injurious fall is a serious hospital-acquired condition. Screening
      tools for injurious falls in hospitalized patients have received limited
      evaluation. OBJECTIVE: To compare operating characteristics of a succinct
      screening tool for injurious falls, the University of Pittsburgh Medical Center
      (UPMC) screening tool (based on mobility, fall history, and nursing judgment),
      with the ABCS injurious fall screening tool (based on Age, Bone, Coagulation, and
      recent Surgery). DESIGN: Case control study. METHODS: Hospitalized patients with
      injurious falls were identified from the UPMC adverse events database for 2007
      2008 (N = 43). Controls (n = 86) matched for age, location, and period of fall
      event were selected from the hospital's administrative database. Tools were
      evaluated independently by 2 screeners using electronic charts. Interrater
      agreement, sensitivity, specificity, positive predictive value (PPV), negative
      predictive value (NPV), and c-statistics for the screening tools were calculated.
      RESULTS: Case and control groups were similar in age, sex, and race. Interrater
      agreement was 71% for ABCS and 72% for UPMC screens. ABCS and UPMC screens had
      sensitivity of 60.5% (95% CI, 52.0%-68.9%) and 62.8% (95% CI, 54.5%-71.1%),
      specificity of 41.9% (95% CI, 33.4%-50.4%) and 58.1% (95% CI 49.6%-66.7%), and c
      statistics of 51.2% and 59.3%, respectively. With a 33% prevalence of injurious
      fall, the PPV was 34.2%, and NPV was 67.9% for ABCS, and the PPV was 42.9%, and
      NPV was 75.8% for UPMC. Operating characteristics were not statistically
      significantly different, although the UPMC screen was 8% more accurate in
      predicting injurious falls and had a lower false-positive rate (44.2% versus
      65.1%). CONCLUSIONS: Compared with the ABCS screen, the UPMC screen is a simple,
      practical tool. Prospective studies are needed to establish the UPMC tool's
      predictive value in hospital practices with lower rates of injurious falls. In
      general, better screening tools for injurious falls should be developed to meet
      quality standards.

PMID- 23149692
TI  - Inpatient fall prevention: use of in-room Webcams.
AB  - OBJECTIVES: Patient falls are a challenging safety and quality issue in acute
      care settings. This study compared inpatient falls on medical-surgical units with
      and without Webcams and assessed the Morse Risk Assessment (MRA) for
      effectiveness in identifying fall risk. METHODS: Ten hospitals in one health
      system that exceeded the benchmark for falls were chosen for a 6-month study. One
      medical-surgical unit in each of the 10 hospitals was randomly assigned to an
      intervention or control group. The intervention group used Webcams that viewed
      the bed with a central monitoring system. A "virtual bed rail" function was used
      for those patients with a Morse Risk Assessment (MRA) of greater than 25.
      RESULTS: Consent rate was 20.7% for the intervention group. A significant
      difference (P <= 0.05) between groups was found in fall rate per 1000 admissions,
      but no significant difference was found in fall rate per 1000 patient days. The
      Morse Risk Assessment was a significant predictor of risk. CONCLUSIONS: Webcams
      are one option to increase surveillance for high-risk patients. The use of the
      MRA with a 50+ score for high risk is recommended. More research is needed on
      patient acceptance of this form of intervention and effectiveness in preventing
      falls on various inpatient units or with specific age groups.

PMID- 23149693
TI  - Detection of systemic and mucosal HPV-specific IgG and IgA antibodies in
      adolescent girls one and two years after HPV vaccination.
AB  - The bivalent HPV16/18 vaccine induces high antibody concentrations in serum while
      data about antibody responses in the cervix are limited. In this study, we
      investigated pre- and post-vaccination antibody responses against seven high-risk
      HPV types by detection of IgG and IgA HPV-specific antibodies in cervical
      secretion samples (CVS) and serum. From an HPV vaccine monitoring study CVS and
      serum samples were available (pre-vaccination (n = 297), one year (n = 211) and
      two years (n = 141) post-dose-one vaccination) from girls aged 14-16 y. The girls
      were vaccinated with the bivalent HPV vaccine at months 0, 1 and 6. CVS was self
      sampled using a tampon. Samples were tested for HPV-specific antibodies
      (HPV16/18/31/33/45/52/58) by a VLP-based multiplex immunoassay. Post-vaccination,
      IgG and IgA antibody levels for HPV16/18 were detectable in CVS and amounted to
      2% and 1% of the IgG and IgA antibody levels observed in serum, respectively. The
      antibody levels remained constant between one and two years after vaccination.
      The correlation between CVS and serum was similar for IgG and IgA vaccine-derived
      antibody levels for HPV16 (rs = 0.58, rs = 0.54) and HPV18 (rs = 0.50, rs =
      0.55). Vaccine-derived IgG antibody levels against cross-reactive HPV types in
      CVS and in serum were highest for HPV45. No IgA cross-reactive antibody responses
      could be detected in CVS. Post-vaccination, HPV16/18 IgG and IgA antibodies are
      not only detectable in serum but also in CVS. The correlation of HPV16/18 IgG
      antibody levels between serum and CVS suggests that vaccine induced HPV
      antibodies transudate and/or exudate from the systemic circulation to the
      cervical mucosa to provide protection against HPV infections. 

PMID- 23149694
TI  - Time-dependent network analysis reveals molecular targets underlying the
      development of diet-induced obesity and non-alcoholic steatohepatitis.
AB  - Prolonged high-fat diet leads to the development of obesity and multiple
      comorbidities including non-alcoholic steatohepatitis (NASH), but the underlying
      molecular basis is not fully understood. We combine molecular networks and time
      course gene expression profiles to reveal the dynamic changes in molecular
      networks underlying diet-induced obesity and NASH. We also identify hub genes
      associated with the development of NASH. Core diet-induced obesity networks were
      constructed using Ingenuity pathway analysis (IPA) based on 332 high-fat diet
      responsive genes identified in liver by time course microarray analysis (8 time
      points over 24 weeks) of high-fat diet-fed mice compared to normal diet-fed mice.
      IPA identified five core diet-induced obesity networks with time-dependent gene
      expression changes in liver. These networks were associated with cell-to-cell
      signaling and interaction (Network 1), lipid metabolism (Network 2), hepatic
      system disease (Network 3 and 5), and inflammatory response (Network 4). When we
      merged these core diet-induced obesity networks, Tlr2, Cd14, and Ccnd1 emerged as
      hub genes associated with both liver steatosis and inflammation and were altered
      in a time-dependent manner. Further, protein-protein interaction network analysis
      revealed Tlr2, Cd14, and Ccnd1 were interrelated through the ErbB/insulin
      signaling pathway. Dynamic changes occur in molecular networks underlying diet
      induced obesity. Tlr2, Cd14, and Ccnd1 appear to be hub genes integrating
      molecular interactions associated with the development of NASH. Therapeutics
      targeting hub genes and core diet-induced obesity networks may help ameliorate
      diet-induced obesity and NASH.

PMID- 23149695
TI  - Study of the DNA damage checkpoint using Xenopus egg extracts.
AB  - On a daily basis, cells are subjected to a variety of endogenous and
      environmental insults. To combat these insults, cells have evolved DNA damage
      checkpoint signaling as a surveillance mechanism to sense DNA damage and direct
      cellular responses to DNA damage. There are several groups of proteins called
      sensors, transducers and effectors involved in DNA damage checkpoint signaling
      (Figure 1). In this complex signaling pathway, ATR (ATM and Rad3-related) is one
      of the major kinases that can respond to DNA damage and replication stress.
      Activated ATR can phosphorylate its downstream substrates such as Chk1
      (Checkpoint kinase 1). Consequently, phosphorylated and activated Chk1 leads to
      many downstream effects in the DNA damage checkpoint including cell cycle arrest,
      transcription activation, DNA damage repair, and apoptosis or senescence (Figure
      1). When DNA is damaged, failing to activate the DNA damage checkpoint results in
      unrepaired damage and, subsequently, genomic instability. The study of the DNA
      damage checkpoint will elucidate how cells maintain genomic integrity and provide
      a better understanding of how human diseases, such as cancer, develop. Xenopus
      laevis egg extracts are emerging as a powerful cell-free extract model system in
      DNA damage checkpoint research. Low-speed extract (LSE) was initially described
      by the Masui group. The addition of demembranated sperm chromatin to LSE results
      in nuclei formation where DNA is replicated in a semiconservative fashion once
      per cell cycle. The ATR/Chk1-mediated checkpoint signaling pathway is triggered
      by DNA damage or replication stress. Two methods are currently used to induce the
      DNA damage checkpoint: DNA damaging approaches and DNA damage-mimicking
      structures. DNA damage can be induced by ultraviolet (UV) irradiation, gamma
      irradiation, methyl methanesulfonate (MMS), mitomycin C (MMC), 4-nitroquinoline-1
      oxide (4-NQO), or aphidicolin. MMS is an alkylating agent that inhibits DNA
      replication and activates the ATR/Chk1-mediated DNA damage checkpoint. UV
      irradiation also triggers the ATR/Chk1-dependent DNA damage checkpoint. The DNA
      damage-mimicking structure AT70 is an annealed complex of two oligonucleotides
      poly-(dA)70 and poly-(dT)70. The AT70 system was developed in Bill Dunphy's
      laboratory and is widely used to induce ATR/Chk1 checkpoint signaling. Here, we
      describe protocols (1) to prepare cell-free egg extracts (LSE), (2) to treat
      Xenopus sperm chromatin with two different DNA damaging approaches (MMS and UV),
      (3) to prepare the DNA damage-mimicking structure AT70, and (4) to trigger the
      ATR/Chk1-mediated DNA damage checkpoint in LSE with damaged sperm chromatin or a
      DNA damage-mimicking structure.

PMID- 23149697
TI  - Thirty years of progress in cutaneous lymphoma research.
AB  - Primary cutaneous lymphomas are a heterogeneous group of T-cell and B-cell
      neoplasms that present in the skin without any evidence of extracutaneous disease
      at the time of diagnosis. In 1980 primary cutaneous lymphomas other than mycosis
      fungoides, Sezary syndrome and some related disorders, collectively termed
      cutaneous T-cell lymphoma had not yet been recognized. This historic review
      describes the history of cutaneous lymphoma research in Europe over the last
      thirty years. European collaborative studies by dermatologists and pathologists,
      often coordinated by the European Organization for Research and Treatment of
      Cancer (EORTC) Cutaneous Lymphoma Group, resulted in the definition of new types
      of cutaneous T-cell lymphomas (CTCL) and cutaneous B-cell lymphomas (CBCL), and
      the development of consensus classifications for primary cutaneous lymphomas
      (EORTC classification; WHO-EORTC classification; WHO classification 2008), which
      resulted in better diagnosis and treatment of these diseases. More recent
      activities described herein are the development of guidelines for staging,
      treatment and the design of clinical trials, often in close collaboration with
      the International Society for Cutaneous Lymphomas, the formation of an EORTC CTCL
      trials platform and attempts to translate the results of molecular genetic
      studies into clinical practise. In this review the importance of a
      multidisciplinary approach and continued international collaboration not only in
      clinical trials and guideline development, but also in basic research is
      emphasized.

PMID- 23149696
TI  - Personality traits, interpersonal identity, and relationship stability:
      longitudinal linkages in late adolescence and young adulthood.
AB  - Adolescence and young adulthood are characterized by important changes in
      personality, changes toward a more stable identity, and the establishment of
      intimate relationships. We examined the role of personality traits in
      establishing intimate relationships, the interplay between personality traits and
      interpersonal identity processes during these relationships, and the role of
      interpersonal identity processes and personality traits in the dissolution
      thereof. For this purpose, we used longitudinal data on 424 female college
      students (mean age at T1 = 18.6 years; Sample 1) and 390 late adolescents drawn
      from a community sample (56.7% female; mean age at T1 = 19.7 years; Sample 2).
      Especially highly extraverted individuals were likely to become involved in a
      relationship. Neuroticism was associated negatively, and Agreeableness and
      Conscientiousness were associated positively with a stronger sense of
      interpersonal identity within intimate relationships. Finally, the importance of
      interpersonal identity processes was underscored by the fact that these
      processes, and not so much personality traits, predicted relational breakups.
      Overall, the present study provides important insights into the role of
      personality and identity in the initiation, maintenance, and dissolution of
      intimate relationships in late adolescence and young adulthood.

PMID- 23149698
TI  - Mycosis fungoides: disease evolution of the "lion queen" revisited.
AB  - Mycosis fungoides (MF), which represents the most common subtype of primary
      cutaneous T-cell lymphoma (CTCL), is an epidermotropic lymphoma included as an
      indolent form in the recent WHO/EORTC classification. From a clinical point of
      view, the classic disease progression usually is slow and takes over years or
      even decades, and characterized by the evolution from patches to more infiltrated
      plaques and eventually to tumours or erythroderma. However, the analysis of the
      MF disease course has been greatly impaired by the rarity of the disease, thus
      data about the time course of disease progression and pattern of relapse during
      time are not well known. In this review, a summary of published data on MF large
      patients cohorts will be presented, together with the results obtained by a
      retrospective analysis of clinical features and follow-up data of 1,422 MF
      patients diagnosed and followed-up from 1975 to 2010 in 27 Italian Centres
      (Italian Study Group for Cutaneous Lymphoma). From a clinical perspective, the
      amount of data support the relevance of a stage-tailored, differentiated follow
      up strategy, in as much as the TNMB staging appears not only to be associated
      with different progression rates, but also shows as a new finding a relationship
      with different patterns of disease progression. From a biological point of view,
      there is the need to understand the molecular basis of the different clinical
      pathways of disease progression, to be able to potentially identify at an earlier
      phase of disease evolution, the patients who are more likely to develop
      erythroderma or tumour-stage progression. In conclusion, if MF is indeed a true
      "lion queen", as dermatologists we need to be expert and wise tamers to keep it
      under control.

PMID- 23149699
TI  - Erythrodermic CTCL: updated clues to diagnosis and treatment.
AB  - Erythroderma is a rare but severe cutaneous condition characterized from a
      clinical point of view by a complete involvement (as per definition more than 80%
      body surface) of the skin surface. Pre-existing dermatoses account for about 70%
      of erythroderma cases, drug reactions are responsible for erythroderma in about
      20%, whilst primary cutaneous T-cell lymphoma (CTCL) constitute less than 10% of
      and are represented by erythrodermic mycosis fungoides and Sezary syndrome. The
      challenge in these patients is represented by the identification of the
      etiological agents or conditions, which is clearly of overwhelming relevance in
      the clinical management and treatment strategies. In recent years, the
      development of multiparameter flow-cytometry, which allows to identify specific
      antigens expressed or not expressed on the surface of atypical lymphoid T-cells,
      and T-cell molecular biology techniques, which are aimed to identify the presence
      of a clonal T-cell population in the skin and blood on the basis of the finding
      of rearrangement of the T-cell receptor, have represented relevant useful tool in
      the differential diagnosis between benign and lymphomatous erythroderma.
      Moreover, a better understanding of the immunological and molecular pathways in
      CTCL disease evolution provided the identification of specific therapeutical
      targets, as well as the constant improvement in the laboratory techniques lead to
      the development of new and promising agents in CTCL.

PMID- 23149700
TI  - CD30+ lymphoproliferative disorders of the skin: still an open question.
AB  - CD30+ lymphoproliferative disorders of the skin represent a well-defined spectrum
      of primary cutaneous T-cell lymphomas. They include lymphomatoid papulosis and
      cutaneous anaplastic large-cell lymphoma which are characterized by the common
      expression of the CD30 antigen, but different clinical, histological and
      molecular features. Recent progress in the pathobiology and identification of
      therapeutic targets has contributed to our current understanding of this peculiar
      group of cutaneous lymphoproliferative disorders. The characteristic features of
      this group of cutaneous lymphoproliferative disorders are reviewed with
      particular emphasis to their diagnosis and treatment strategies.

PMID- 23149701
TI  - Cutaneous peripheral T-cell lymphomas, unspecified/NOS and rare subtypes: a
      heterogeneous group of challenging cutaneous lymphomas.
AB  - Cutaneous peripheral T-cell lymphoma, unspecified/not otherwise specified (PTL
      NOS) represents a phenotypically and prognostically heterogenous group of
      cutaneous T-cell lymphomas (CTCL) that do not fit into any of well defined
      defined CTCL subtypes. In the WHO-EORTC classification as well as the WHO
      classification, three entities have been delineated as provisional rare subtypes
      of PTL based on their characteristic clinico-pathological, immunophenotypic and
      prognostic features and have been separated out from PTL, NOS: Primary cutaneous
      CD4-positive small/medium T-cell lymphoma (CD4+ SMTL), primary cutaneous CD8
      positive aggressive epidermotropic T-cell lymphoma (CD8+ AECTCL), and primary
      cutaneous gamma/delta T-cell lymphoma (CGD-TCL). CD4+ SMTL manifests in most
      patients with a solitary nodule in the head and neck area and nodular infiltrates
      of CD4+ small to medium-sized lymphocytes with nuclear pleomorphism. The
      prognosis of this lymphoproliferation is excellent in patients with a solitary
      lesion, but may be impaired in patients with multifocal disease. Rapidly evolving
      erosive or necrotic plaques and nodules with an epidermotropic infiltrate of CD8+
      atypical lymphocytes are the hallmark of CD8+ AECTCL, which exhibits a poor
      prognosis. CGD-TCL displays a broad spectrum of clinical and histological
      manifestations with expression of the T-cell receptor gamma/delta chain as the
      common denominator and diagnostic marker. As most of other forms of PTL, CGD-TCL
      carries a poor prognosis. Despite the rarity of PTL NOS, clinicians as well as
      dermatopathologists and pathologists should be familiar with these rare CTC,
      especially since most of these lymphomas exhibit an unfavourable prognosis.
      Immediate intense treatment with multiagent chemotherapy and hematopoietic stem
      cell transplantation is indicated in patients with PTL NOS. This review focuses
      on the clinicopathological aspects, the diagnostic criteria and the
      classification of the rare subtypes of PTL and PTL NOS.

PMID- 23149702
TI  - Advanced/aggressive CTCL: improving the efficacy of treatment.
AB  - Treatment regimens of patients with cutaneous T-cell lymphoma (CTCL) vary widely
      based on clinician preference and patient tolerance. Skin directed therapies are
      recommended for patients with early stage IA and IB MF, with combinations used in
      refractory cases. While no regimen has been proven to prolong survival in
      advanced stages, immunomodulatory regimens should be used initially to reduce the
      need for cytotoxic therapies. In more advanced stages of disease, treatment
      efforts should strive for palliation and improvement of quality of life. With
      many new therapies and strategies on the horizon, the future looks promising for
      CTCL patients.

PMID- 23149703
TI  - Combination treatment in CTCL: the current role of bexarotene.
AB  - Primary cutaneous T-cell lymphomas are a heterogeneous group of extranodal NH
      lymphomas primarily presenting in the skin without extracutaneos involvement at
      diagnosis. Treatment choices closely depend on clinic-pathologic entity and
      disease stage. Among available choices, oral bexarotene has shown efficacy and
      safety both in monotherapy and in association with other treatments, by virtue of
      its versatility and high synergism with alpha-interferon, photochemotherapy
      (PUVA), and chemotherapy. Moreover, when associated with a wise management of its
      side effects, bexarotene is well tolerated if used in long-term administration,
      and it is therefore a good candidate to maintenance treatment after different
      induction therapies. Recently, the Gruppo Italiano Linfomi Cutanei (GILC) has
      started some pilot studies, with the aim to investigate bexarotene potential in
      association with PUVA and single agent chemotherapy (as pegylated liposomal
      doxorubicin and gemcitabine), and as consolidation/maintenance treatment. The
      preliminary results of GILC pilot studies confirm the good tolerability and
      safety of low-intermediate dose bexarotene, and its potential synergism with PUVA
      and chemotherapy. In addition, its use in consolidation/maintenance has proven
      efficacy in improving overall response rate.

PMID- 23149704
TI  - Indolent cutaneous B-cell lymphoma: diagnosis and treatment 2012.
AB  - Among primary cutaneous B-cell lymphomas (CBCL), two main clinico-pathologic
      entities are recognized, i.e. marginal zone lymphoma (MZL), otherwise defined as
      extranodal MZL, MALT (Mucosa-Associated Lymphoid Tissue) type, and follicle
      center lymphoma (FCL). They are mostly characterized by indolent course (very
      limited risk of extracutaneous spread), very good response to non-aggressive
      treatment (radiotherapy is the gold standard), and excellent prognosis (>90% 5
      year survival overall). The clinical presentation of MZL and FCL slightly differ
      concerning site predilection (trunk and upper limbs in the former, head&neck and
      trunk in the latter) and frequency of cases with multiple, non-contiguous lesions
      (higher in MZL). Histologically, MZL and FCL share the multiphasic evolution of
      lesions, while some distinctive features are clues to diagnosis and differential
      diagnosis: CD5-/CD10-/bcl2+ phenotype of neoplastic cells, "colonization" of
      reactive lymphoid follicles by neoplastic cells, lymphoplasmacytoid and plasma
      cells at the periphery of nodular infiltrates in MZL; CD5-, CD10 +/-, bcl6+, MUM
      1 neg, FOX-P1 neg, IRF4 neg, IgM neg phenotype of neoplastic cells (centrocytes),
      and neoplastic follicles (in early lesions) in FCL.

PMID- 23149705
TI  - Primary cutaneous diffuse large B-cell lymphoma (PCDLBCL), leg-type and other: an
      update on morphology and treatment.
AB  - Primary cutaneous B-cell lymphoma (PCBCL) is an heterogeneous group of
      lymphoproliferative disorders, which account for 25-30% of all primary cutaneous
      lymphoma and include three main histotypes: 1) primary cutaneous marginal zone B
      cell lymphoma (PCMZL); 2) primary cutaneous follicular center cell lymphoma
      (PCFCL); 3) primary cutaneous diffuse large B-cell lymphoma (DLBCL), leg type
      (PCDLBCL-LT). PCMZL and PCFCL are indolent lymphomas, with an excellent prognosis
      despite an high rate of cutaneous recurrences; in contrast, PCDLBCL-LT is
      clinically more aggressive and usually requires to be treated with multi-agent
      chemotherapy and anti-CD20 monoclonal antibodies. PCDLBCL-LT histologically
      consists of large round cells (centroblasts and immunoblasts), is characterized
      by strong bcl-2 expression, in the absence of t(14;18) translocation, and
      resembles the activated B-cell type of nodal DLBCL. Recently, the term primary
      cutaneous DLBCL-other (PCDLBCL-O) has been proposed to include diffuse lymphomas
      composed of large transformed B-cells that lack the typical features of PCDLBCL
      LT and do not conform to the definition of PCFCL. Some clinical studies suggested
      that such cases have an indolent clinical course and may be treated in a
      conservative manner; however, data regarding the actual prognosis and clinical
      behaviour of these peculiar cases are still too limited. The spectrum of primary
      cutaneous DLBCL also encompasses some rare morphological variants, such as
      anaplastic or plasmablastic subtypes and T-cell rich B-cell lymphoma, and some
      recently described, exceedingly rare DLBCL subtypes, such as intravascular large
      B-cell lymphoma and EBV-associated large B-cell lymphoma of the elderly, which
      often present in the skin.

PMID- 23149706
TI  - Blastic plasmacytoid dendritic cell neoplasm (BPDCN): the cutaneous sanctuary.
AB  - AIM: Blastic plasmacytoid dendritic cell neoplasm (BPDNC) is a rare tumour, which
      stems from plasmacytoid dendritic cells. Although the aetiology is still unclear,
      in the last few years various reports suggested a potential role of chromosomal
      aberrations in the oncogenesis. The disease is currently enclosed among "acute
      myeloid leukemia (AML) and related precursor neoplasms" in the last WHO
      classification. BPDCN has an aggressive course, however, it has been suggested
      that an exclusive cutaneous involvement at presentation is related to a better
      clinical outcome. METHODS: We review the literature about BPDCN, and we present a
      series of 11 cases, all characterised by disease limited to the skin at
      presentation. Furthermore, we examined all cases of the last 10 years stored in
      the database of the multidisciplinary study group on cutaneous lymphomas of the
      University of Florence. RESULTS: Basing on the clinical features, patient were
      classified into two groups: with a single-lesion or multiple eruptive-lesions
      presentation. The former were treated with radiotherapy (limited field, electron
      beam therapy). The latter were treated with different therapeutic options,
      depending on age and co-morbidities. All patients with a single lesion achieved
      complete response. Five of 6 patients with eruptive lesions achieved a clinical
      response (2 complete and 3 partial response). Notably, the progression free
      survival was higher in the single-lesion than in the eruptive-lesion group (23
      vs. 9 months). However all patients relapsed and 8 of 11 died. CONCLUSION:
      Although the small number of selected patients, we could speculate that the
      concept of "cutaneous sanctuary" is particularly true in patients with a single
      lesion-presentation. In these patients, especially if >70 year-old aged,
      radiotherapy should be encouraged as the treatment of choice.

PMID- 23149707
TI  - Consensus on the use of the fixed combination calcipotriol/betamethasone
      dipropionate in the treatment of plaque psoriasis.
AB  - Calcipotriol, a vitamin D analogue, and betamethasone dipropionate, a high
      potency corticosteroid, are complementary agents for the topical treatment of
      psoriasis vulgaris. Robust evidence on the efficacy and safety of their fixed
      combination has been provided by randomized, double-blind, controlled clinical
      trials involving more than 7000 patients with the ointment formulation in
      psoriasis of the body and more than 4000 patients with the gel formulation in
      scalp psoriasis. These trials have shown that the fixed combination ointment is
      more effective and better tolerated, not only than placebo, but also than
      calcipotriol and tacalcitol monotherapies. In addition, it has proved, in most
      instances, to be more effective than betamethasone and at least as well
      tolerated. The same applies to the gel for scalp and body psoriasis. Safety
      studies have excluded that repeated courses of treatment with the fixed
      combination for up to one year produce systemic effects. Studies have also shown
      that the fixed combination treatment improves quality of life to a significantly
      greater extent than calcipotriol, with the once daily regimen most appreciated by
      patients, in both active disease and recurrency. Because of the extensive
      evidence, American and European guidelines recommend the
      calcipotriol/betamethasone dipropionate fixed combination as first line topical
      treatment for mild to moderate plaque psoriasis of the body and scalp.

PMID- 23149708
TI  - Efficacy of Iralfaris shampoo in the treatment of scalp psoriasis: a
      videodermoscopy evaluation prospective study in 70 patients.
AB  - AIM: This work has the aim to test the sensibility of VSCAPSI method in the
      evaluation of effectiveness of a medicated shampoo for the treatment of scalp
      psoriasis. Psoriasis is a chronic inflammatory skin disease histologically
      characterized by proliferation and loss of differentiation of keratinocytes,
      angiogenesis with vasodilatation and increased permeability, and inflammation.
      Scalp involvement is a common clinical feature of psoriasis, that is present in
      the 25% of patients who suffer of it. Videodermoscopy (VD) permits a magnified
      view of the surface components of the epidermis and papillary dermis, which are
      not visible to the naked eye, together with the ability to capture digitally the
      viewed images and to store them for later use. Moreover videodermoscopy is a non
      invasive technique, used to analyze cutaneous peripheral microcirculation.
      Therefore VD could be an useful tool in evaluating the efficacy of treatments for
      scalp psoriasis. The clinical benefit of currently available medicated shampoos
      for the treatment of scalp psoriasis is restricted, due to their limited
      efficacy, low cosmetic appeal and safety and tolerability problems. Therefore
      effective and safe products are needed especially for the long term management of
      scalp psoriasis. A specific shampoo designed for the scalp hygiene in psoriatic
      patients has been recently developed. This shampoo contains urea, glycolic acid,
      salicylic acid, icthyol pale and laureth 9 (polidocanol). Aim of the study was to
      evaluate in a 12-week prospective monocenter, open-study the efficacy and
      tolerability of an emollient, keratolytic shampoo (Iralfaris shampoo ISDIN,
      Barcelona; Ir-S) applied three times a week in patients with scalp psoriasis. The
      efficacy of the shampoo has been valuated with VSCAPSI. METHODS: Seventy subjects
      with mild to moderate/severe scalp psoriasis were enrolled in the trial, after
      their informed consent. Efficacy was assessed using a specific and validated
      videodermoscopy scalp psoriasis severity index (VSCAPSI) score, performed at
      baseline, after 45 and 90 days. Patients were evaluated for itching. RESULTS:
      VSCAPSI score at baseline was 8.5. Ir-S induced a significant reduction of
      VSCAPSI score in comparison with baseline value both after 45 and 90 days of
      treatment. The use of shampoo lead to a progressive reduction of VSCAPSI score
      getting a score of 4.2 at T45 and a score of 4.0 at T90 (P=0.001 vs. baseline).
      The use of Ir-S has significantly reduced the percentage of patients reporting
      itching sensation. CONCLUSION: The treatment was safe and well-tolerated with an
      high cosmetic acceptance. Ir-S is a good alternative to other medicated shampoo
      in the treatment of mild to moderate scalp psoriasis. Moreover, in the treatment
      of severe scalp psoriasis, it can lead to an improvement if associated with
      topical medications.

PMID- 23149709
TI  - Skin diseases in geriatric patients: our experience from a public skin outpatient
      clinic in Siena.
AB  - AIM: With the progressive aging of the Italian population, geriatric health care
      has become a major issue for health authorities. However, little data is
      available regarding geriatric skin diseases. In order to provide rapid access to
      specialist help, in 2003 we created a dermatology clinic dedicated only to
      geriatric patients age 65 and older. METHODS: To determine the characteristic
      pattern and the prevalence of various skin disorders among the geriatric patients
      seen at the clinic, we performed a retrospective and descriptive study of all
      skin diseases in patients seen in our office from January 2003 to December 2009.
      We evaluated: age, proportion and gender for all skin disease categories.
      RESULTS: A total of 2100 geriatric patients were examined. The male to female
      ratio was 1.4 to 1. The most common disorder was pruritus "sine materia" (18.9%)
      followed by benign tumors (13.5%); 9.1% of our patients presented with actinic
      keratoses and 13.2% with malignant tumors. As reported by others, the quality of
      life in patients with skin cancer was better than patients with rashes as skin
      cancer patients tended to wait longer before seeking specialist care. To improve
      the assessment of skin diseases, we often worked closely with CONCLUSION: The
      prevalence of skin diseases in our patients emphasized the importance of
      educating the elderly about sun protection, the early detection of skin cancer,
      the use of emollients and proper skin care in general.

PMID- 23149710
TI  - Vitiligo: recent insights and new therapeutic approaches.
AB  - Vitiligo represents a selective destruction of the melanocytes. It is a
      relatively common, probably autoimmune disorder that affects people of all
      backgrounds and both genders. No particular group seems to be preferentially
      affected. Half of vitiligo patients have an onset before the age of 18 years. In
      regions where leprosy is endemic, individuals with vitiligo are often stigmatized
      due to similarities in appearance between the two diseases. We will review this
      important subject, emphasizing the latest therapeutic advances.

PMID- 23149711
TI  - Appearance of a reservoir of hookworm-related cutaneous larva migrans in
      Brittany?
AB  - We describe two cases of hookworm-related cutaneous larva migrans acquired in
      Brittany (North-Western France). The patients were a 23-year-old woman and a 28
      year-old man. In both patients the feet were involved. In the second patient, a
      superinfection due to Staphylococcus aureus was recorded. The appearance in
      Brittany of a reservoir of nematodes capable of causing hookworm-related
      cutaneous larva migrans is hypothesized.

PMID- 23149712
TI  - Cutaneous neonatal lupus: two cases.

PMID- 23149713
TI  - Bullous pemphigoid of lever and celiac disease: a coincidental occurrence or an
      unusual association?

PMID- 23149714
TI  - Control of the harmful alga Microcystis aeruginosa and absorption of nitrogen and
      phosphorus by Candida utilis.
AB  - This study is aimed at controlling eutrophication through converting the
      nutrients such as nitrogen and phosphorus into microbial protein and
      simultaneously inhibiting the growth of Microcystis aeruginosa by Candida utilis.
      C. utilis and M. aeruginosa (initial cell density was 2.25 * 10(7) and 4.15 *
      10(7) cells.mL(-1)) were cultured together in the absence or presence of a carbon
      source (glucose) during a 10-day experiment. In the absence of carbon source, the
      measured removal efficiencies of NH(4) (+)-N and PO(4) (3-)-P were 41.39 +/- 2.19
      % and 82.93 +/- 3.95 %, respectively, at the second day, with the removal
      efficiency of 67.82 +/- 2.29 % for M. aeruginosa at the fourth day. In contrast,
      the removal efficiencies of NH(4) (+)-N and PO(4) (3-)-P were increased to 87.45
      +/- 4.25 % and 83.73 +/- 3.55 %, respectively, while the removal efficiency of M.
      aeruginosa decreased to 37.89 +/- 8.41 % in the presence of the carbon source
      (C/N = 2:1). These results showed that the growth of M. aeruginosa was inhibited
      by C. utilis. Our finding sheds light on a novel potential approach for yeast to
      consume nutrients and control harmful algal during bloom events.

PMID- 23149715
TI  - Extracellular enzymes of the white-rot fungus Fomes fomentarius and purification
      of 1,4-beta-glucosidase.
AB  - Production of the lignocellulose-degrading enzymes endo-1,4-beta-glucanase, 1,4
      beta-glucosidase, cellobiohydrolase, endo-1,4-beta-xylanase, 1,4-beta-xylosidase,
      Mn peroxidase, and laccase was characterized in a common wood-rotting fungus
      Fomes fomentarius, a species able to efficiently decompose dead wood, and
      compared to the production in eight other fungal species. The main aim of this
      study was to characterize the 1,4-beta-glucosidase produced by F. fomentarius
      that was produced in high quantities in liquid stationary culture (25.9 U ml(
      1)), at least threefold compared to other saprotrophic basidiomycetes, such as
      Rhodocollybia butyracea, Hypholoma fasciculare, Irpex lacteus, Fomitopsis
      pinicola, Pleurotus ostreatus, Piptoporus betulinus, and Gymnopus sp. (between
      0.7 and 7.9 U ml(-1)). The 1,4-beta-glucosidase enzyme was purified to
      electrophoretic homogeneity by both anion-exchange and size-exclusion
      chromatography. A single 1,4-beta-glucosidase was found to have an apparent
      molecular mass of 58 kDa and a pI of 6.7. The enzyme exhibited high
      thermotolerance with an optimum temperature of 60  degrees C. Maximal activity
      was found in the pH range of 4.5-5.0, and K (M) and V (max) values were 62 MUM
      and 15.8 MUmol min(-1) l(-1), respectively, when p-nitrophenylglucoside was used
      as a substrate. The enzyme was competitively inhibited by glucose with a K (i) of
      3.37 mM. The enzyme also acted on p-nitrophenylxyloside, p
      nitrophenylcellobioside, p-nitrophenylgalactoside, and p-nitrophenylmannoside
      with optimal pH values of 6.0, 3.5, 5.0, and 4.0-6.0, respectively. The
      combination of relatively low molecular mass and low K (M) value make the 1,4
      beta-glucosidase a promising enzyme for biotechnological applications.

PMID- 23149716
TI  - Enzymatic characterization of human immunodeficiency virus type 1 reverse
      transcriptase for use in cDNA synthesis.
AB  - The aim of this study is to explore the advantages of using human
      immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) in cDNA
      synthesis. Recombinant HIV-1 group M (HIV-1 M) RT and HIV-1 group O (HIV-1 O) RT
      were produced in an Escherichia coli expression system. In the incorporation of
      dTTP into poly(rA)-p(dT)(15) (T/P), the K (m) values for dTTP of HIV-1 M RT and
      HIV-1 O RT were 8 and 12 % of that of Moloney murine leukemia virus (MMLV) RT,
      respectively, and the K (m) values for T/P were 25 and 23 % of that of MMLV RT,
      respectively. Compared with MMLV RT, HIV-1 M RT and HIV-1 O RT were less
      susceptible to formamide, which is frequently used for cDNA synthesis with a G +
      C-rich RNA to improve specificity. The high substrate affinity and low
      susceptibility to formamide of HIV-1 RT might be advantageous for its use in cDNA
      synthesis.

PMID- 23149717
TI  - Lentiviral-mediated over-expression of hyaluronan synthase-1 (HAS-1) decreases
      the cellular inflammatory response and results in regenerative wound repair.
AB  - Fetal wounds have been found to have increased levels of high-molecular-weight
      hyaluronan (HMW-HA) compared with those of adults. The primary enzyme responsible
      for producing HMW-HA is hyaluronic acid synthase-1 (HAS-1). We hypothesized that
      over-expression of HAS-1 in adult dermal wounds would decrease inflammation and
      promote regenerative healing. To test this hypothesis, the flanks of adult
      C57Bl/6 mice were treated with a lentiviral construct containing either HAS-1-GFP
      or GFP transgenes. After 48 h, a 4-mm excisional wound was made at the site of
      treatment. Wounds were harvested at days 3, 7, or 28 after wounding. Wound
      phenotype was assessed by histology to examine tissue architecture and
      immunohistochemistry for CD45. At 7 and 28 days, lenti-HAS-1-treated wounds
      demonstrated the restoration of the normal dermal elements and organized collagen
      fiber orientation. In contrast, the lenti-GFP-treated wounds lacked normal dermal
      architecture and demonstrated a disorganized collagen scar. At 3 and 7 days,
      wounds treated with lenti-HAS-1 exhibited a significant decrease in the number of
      inflammatory cells when compared with wounds treated with lenti-GFP. Thus, HAS-1
      over-expression promotes dermal regeneration, in part by decreasing the
      inflammatory response and by recapitulation of fetal extracellular matrix HMW-HA
      content.

PMID- 23149718
TI  - Gene expression changes in the secondary palate and mandible of Prdm16(-/-) mice.
AB  - Loss of Prdm16 expression in the mouse leads to a complete cleft of the secondary
      palate. We have now determined changes in gene expression in the secondary
      palates of Prdm16(-/-) fetuses in an attempt to reveal the mechanism(s) leading
      to the failure of palate closure in these mice. Defined pathway-based polymerase
      chain reaction arrays were used to analyze the expression of genes associated
      with the extracellular matrix and the transforming growth factor-beta and bone
      morphogenetic protein signaling networks, perturbations of which can lead to
      palatal clefting. Loss of Prdm16 expression in the secondary palate leads to
      alterations in numerous genes within these groups, many of which have been linked
      to chondrogenesis and osteogenesis. The expression of several genes linked to
      bone development was significantly changed in the developing secondary palate.
      Analysis of gene expression in the mandibles of Prdm16(-/-) fetuses revealed
      similar alterations in the same gene set. These data suggest that one function of
      Prdm16 is the regulation of genes that play a role in the differentiation of
      mesenchymal cells into chondro-/osteocytes.

PMID- 23149720
TI  - Antibacterial effect of zinc oxide nanoparticles combined with ultrasound.
AB  - Using Staphylococcus aureus (S. aureus), the present study investigated the
      antibacterial effect of ZnO nanoparticles both in the absence and presence of
      ultrasound stimulation. While the antibacterial effect of control nanoparticle
      chemistries (Al(2)O(3)) alone was either weak or unobservable under the
      conditions tested, the antibacterial effect of ZnO alone was significant,
      providing over a four log reduction (equivalent to antibiotics) compared to no
      treatment after just 8 h. The antibacterial effect was enhanced as ZnO particle
      diameter decreased. Specifically, when testing the antibacterial effect against
      bacteria populations relevant to infection, a 500 MUg ml(-1) dose of zinc oxide
      nanoparticles with a diameter of 20 nm reduced S. aureus populations by four
      orders of magnitude after 8 and 24 h, compared to control groups with no
      nanoparticles. This was accomplished without the use of antibiotics, to which
      bacteria are developing a resistance anyway. The addition of ultrasound
      stimulation further reduced the number of viable colony-forming units present in
      a planktonic cell suspension by 76% compared to nanoparticles alone. Lastly, this
      study provided a mechanism for how ZnO nanoparticles in the presence of
      ultrasound decrease bacteria functions by demonstrating greater hydrogen peroxide
      generation by S. aureus compared to controls. These results indicated that small
      diameter ZnO nanoparticles exhibited strong antibacterial properties that can be
      additionally enhanced in the presence of ultrasound and, thus, should be further
      studied for a wide range of medical device anti-infection applications.

PMID- 23149719
TI  - Developmental changes in the responsiveness of rat spiral ganglion neurons to
      neurotrophic factors in dissociated culture: differential responses for survival,
      neuritogenesis and neuronal morphology.
AB  - The way that the development of the inner ear innervation is regulated by various
      neurotrophic factors and/or their combinations at different postnatal
      developmental stages remains largely unclear. Moreover, survival and
      neuritogenesis in deafferented adult neurons is important for cochlear implant
      function. To address these issues, developmental changes in the responsiveness of
      postnatal rat spiral ganglion neurons (SGNs) to neurotrophin-3 (NT-3), brain
      derived neurotrophic factor (BDNF) and leukemia inhibitory factor (LIF) were
      examined by using a dissociated cell culture system. SGNs at postnatal day (P) 0,
      P5 and P20 (young adult) were cultured with the addition of NT-3, BDNF, or LIF or
      of a combination of NT-3 and BDNF (N + B) or of NT-3, BDNF and LIF (ALL factors).
      SGNs were analyzed for three parameters: survival, longest neurite length (LNL)
      and neuronal morphology. At P0, SGNs required exposure to N + B or ALL factors
      for enhanced survival and the ALL factors combination showed a synergistic effect
      much greater than the sum of the individual factors. At P5, SGNs responded to a
      wider range of treatment conditions for enhanced survival and combinations showed
      only an additive improvement over individual factors. The survival percentage of
      untreated SGNs was highest at P20 but combinations of neurotrophic factors were
      no more effective than individual factors. LNL of each SGN was enhanced by LIF
      alone or ALL factors at P0 and P5 but was suppressed by NT-3, BDNF and N + B at
      P5 in a dose-dependent manner. The LNL at P20 was enhanced by ALL factors and
      suppressed by N + B. Treatment with ALL factors increased the proportion of SGNs
      that had two or more primary neurites in all age groups. These findings suggest
      that NT-3, BDNF, LIF and their combinations predominantly support different
      ontogenetic events at different developmental stages in the innervation of the
      inner ear.

PMID- 23149721
TI  - Heterometallic appended {MMn(III)4} cubanes encapsulated by lacunary
      polytungstate ligands.
AB  - The heterometallic appended {MMn(III)(4)} (M = Dy(3+) and K(+)) cubanes were
      firstly trapped by two diamagnetic POM shells, which were robust enough to
      construct inorganic crystalline tubular materials. Magnetic study reveals the
      presence of a SMM-like slow magnetic relaxation feature in the heterometallic
      cluster-containing POM.

PMID- 23149722
TI  - An arsenic-contaminated field trial to assess the uptake and translocation of
      arsenic by genotypes of rice.
AB  - Compared to other cereals, rice has particular strong As accumulation. Therefore,
      it is very important to understand As uptake and translocation among different
      genotypes. A field study in Chenzhou city, Hunan province of China, was employed
      to evaluate the effect of arsenic-contaminated soil on uptake and distribution in
      34 genotypes of rice (including unpolished rice, husk, shoot, and root). The soil
      As concentrations ranged from 52.49 to 83.86 mg kg(-1), with mean As
      concentration 64.44 mg kg(-1). The mean As concentrations in rice plant tissues
      were different among the 34 rice genotypes. The highest As concentrations were
      accumulated in rice root (196.27-385.98 mg kg(-1) dry weight), while the lowest
      was in unpolished rice (0.31-0.52 mg kg(-1) dry weight). The distribution of As
      in rice tissue and paddy soil are as follows root ? soil > shoot > husk >
      unpolished rice. The ranges of concentrations of inorganic As in all of
      unpolished rice were from 0.26 to 0.52 mg kg(-1) dry weight. In particular, the
      percentage of inorganic As in the total As was more than 67 %, indicating that
      the inorganic As was the predominant species in unpolished rice. The daily
      dietary intakes of inorganic As in unpolished rice ranged from 0.10 to 0.21 mg
      for an adult, and from 0.075 to 0.15 mg for a child. Comparison with tolerable
      daily intakes established by FAO/WHO, inorganic As in most of unpolished rice
      samples exceeded the recommended intake values. The 34 genotypes of rice were
      classified into four clusters using a criteria value of rescaled distance between
      5 and 10. Among the 34 genotypes, the genotypes II you 416 (II416) with the
      lowest enrichment of As and the lowest daily dietary intakes of inorganic As
      could be selected as the main cultivar in As-contaminated field.

PMID- 23149723
TI  - Hydrogeochemistry and statistical analysis applied to understand fluoride
      provenance in the Guarani Aquifer System, Southern Brazil.
AB  - High fluoride concentrations (up to 11 mg/L) have been reported in the
      groundwater of the Guarani Aquifer System (Santa Maria Formation) in the central
      region of the state of Rio Grande do Sul, Southern Brazil. In this area, dental
      fluorosis is an endemic disease. This paper presents the geochemical data and the
      combination of statistical analysis (Principal components and cluster analyses)
      and geochemical modeling to achieve the hydrogeochemistry of the groundwater and
      discusses the possible fluoride origin. The groundwater from the Santa Maria
      Formation is comprised of four different geochemical groups. The first group
      corresponds to a sodium chloride groundwater which evolves to sodium bicarbonate,
      the second one, both containing fluoride anomalies. The third group is
      represented by calcium bicarbonate groundwater, and in the fourth, magnesium is
      the distinctive parameter. The statistical and geochemical analyses supported by
      isotopic measurements indicated that groundwater may have originated from
      mixtures of deeper aquifers and the fluoride concentrations could be derived from
      rock/water interactions (e.g., desorption from clay minerals).

PMID- 23149724
TI  - Chirality-controlled synthesis of single-wall carbon nanotubes using vapour-phase
      epitaxy.
AB  - Chirality-controlled synthesis of single-wall carbon nanotubes with predefined
      chiralities has been an important but elusive goal for almost two decades. Here
      we demonstrate a general strategy for producing carbon nanotubes with predefined
      chiralities by using purified single-chirality nanotubes as seeds for subsequent
      metal catalyst free growth, resembling vapour-phase epitaxy commonly used for
      semiconductor films. In particular, we have successfully synthesized (7, 6), (6,
      5) and (7, 7) nanotubes, and used Raman spectroscopy to show unambiguously that
      the original chiralities of the nanotube seeds are preserved. Furthermore, we
      have performed electrical measurements on synthesized individual (7, 6) and (6,
      5) nanotubes, confirming their semiconducting nature. The vapour-phase epitaxy
      approach is found to be highly robust and should enable a wide range of
      fundamental studies and technological developments.

PMID- 23149725
TI  - Chimpanzees and humans harbour compositionally similar gut enterotypes.
AB  - Microbes inhabiting the human gastrointestinal tract tend to adopt one of three
      characteristic community structures, called 'enterotypes', each of which is
      overrepresented by a distinct set of bacterial genera. Here we report that the
      gut microbiotae of chimpanzees also assort into enterotypes and that these
      chimpanzee enterotypes are compositionally analogous to those of humans. Through
      the analysis of longitudinal samples, we show that the microbial signatures of
      the enterotypes are stable over time, but that individual hosts switch between
      enterotypes over periods longer than a year. These results support the hypothesis
      that enterotypic variation was present in populations of great apes before the
      divergence of humans and chimpanzees.

PMID- 23149726
TI  - Symmetry breaking and optical negative index of closed nanorings.
AB  - Metamaterials have extraordinary abilities, such as imaging beyond the
      diffraction limit and invisibility. Many metamaterials are based on split-ring
      structures, however, like atomic orbital currents, it has long been believed that
      closed rings cannot produce negative refractive index. Here we report a low-loss
      and polarization-independent negative-index metamaterial made solely of closed
      metallic nanorings. Using symmetry breaking that negatively couples the discrete
      nanorings, we measured negative phase delay in our composite 'chess
      metamaterial'. The formation of an ultra-broad Fano-resonance-induced optical
      negative-index band, spanning wavelengths from 1.3 to 2.3 MUm, is experimentally
      observed in this structure. This discrete and mono-particle negative-index
      approach opens exciting avenues towards symmetry-controlled topological
      nanophotonics with on-demand linear and nonlinear responses.

PMID- 23149727
TI  - Determination of monolayer-protected gold nanoparticle ligand-shell morphology
      using NMR.
AB  - It is accepted that the ligand shell morphology of nanoparticles coated with a
      monolayer of molecules can be partly responsible for important properties such as
      cell membrane penetration and wetting. When binary mixtures of molecules coat a
      nanoparticle, they can arrange randomly or separate into domains, for example,
      forming Janus, patchy or striped particles. To date, there is no straightforward
      method for the determination of such structures. Here we show that a combination
      of one-dimensional and two-dimensional NMR can be used to determine the ligand
      shell structure of a series of particles covered with aliphatic and aromatic
      ligands of varying composition. This approach is a powerful way to determine the
      ligand shell structure of patchy particles; it has the limitation of needing a
      whole series of compositions and ligands' combinations with NMR peaks well
      separated and whose shifts due to the surrounding environment can be large
      enough.

PMID- 23149729
TI  - Behavioural and neurobiological implications of linear and non-linear features in
      larynx phonations of horseshoe bats.
AB  - Mammalian vocalizations exhibit large variations in their spectrotemporal
      features, although it is still largely unknown which result from intrinsic
      biomechanical properties of the larynx and which are under direct neuromuscular
      control. Here we show that mere changes in laryngeal air flow yield several non
      linear effects on sound production, in an isolated larynx preparation from
      horseshoe bats. Most notably, there are sudden jumps between two frequency bands
      used for either echolocation or communication in natural vocalizations. These
      jumps resemble changes in 'registers' as in yodelling. In contrast, simulated
      contractions of the main larynx muscle produce linear frequency changes, but are
      limited to echolocation or communication frequencies. Only by combining non
      linear and linear properties can this larynx, therefore, produce sounds covering
      the entire frequency range of natural calls. This may give behavioural meaning to
      yodelling-like vocal behaviour and reshape our thinking about how the brain
      controls the multitude of spectral vocal features in mammals.

PMID- 23149730
TI  - A peptide derived from laminin-gamma3 reversibly impairs spermatogenesis in rats.
AB  - Cellular events that occur across the seminiferous epithelium in the mammalian
      testis during spermatogenesis are tightly coordinated by biologically active
      peptides released from laminin chains. Laminin-gamma3 domain IV is released at
      the apical ectoplasmic specialization during spermiation and mediates
      restructuring of the blood-testis barrier, which facilitates the transit of
      preleptotene spermatocytes. Here we determine the biologically active domain in
      laminin-gamma3 domain IV, which we designate F5 peptide, and show that the
      overexpression of this domain, or the use of a synthetic F5 peptide, in Sertoli
      cells with an established functional blood-testis barrier reversibly perturbs
      blood-testis barrier integrity in vitro and in the rat testis in vivo. This
      effect is mediated via changes in protein distribution at the Sertoli and Sertoli
      germ-cell cell interface and by phosphorylation of focal adhesion kinase at
      Tyr(407). The consequences are perturbed organization of actin filaments in
      Sertoli cells, disruption of the blood-testis barrier and spermatid loss. The
      impairment of spermatogenesis suggests that this laminin peptide fragment may
      serve as a contraceptive in male rats.

PMID- 23149732
TI  - An insect-induced novel plant phenotype for sustaining social life in a closed
      system.
AB  - Foraging, defense and waste disposal are essential for sustaining social insect
      colonies. Hence, their nest generally has an open structure, wherein specialized
      castes called workers and soldiers perform these tasks. However, some social
      aphids form completely closed galls, wherein hundreds to thousands of insects
      grow and reproduce for several months in isolation. Why these social aphids are
      not drowned by accumulated honeydew has been an enigma. Here we report a
      sophisticated biological solution to the waste problem in the closed system: the
      gall inner surface is specialized for absorbing water, whereby honeydew is
      promptly removed via the plant vascular system. The water-absorbing closed galls
      have evolved at least twice independently among social aphids. The plant-mediated
      waste removal, which entails insect's manipulation of plant morphogenesis and
      physiology, comprises a previously unknown mechanism of nest cleaning, which can
      be regarded as 'extended phenotype' and 'indirect social behavior' of the social
      aphids.

PMID- 23149731
TI  - Structural modelling and mutant cycle analysis predict pharmacoresponsiveness of
      a Na(V)1.7 mutant channel.
AB  - Sodium channel Na(V)1.7 is critical for human pain signalling. Gain-of-function
      mutations produce pain syndromes including inherited erythromelalgia, which is
      usually resistant to pharmacotherapy, but carbamazepine normalizes activation of
      Na(V)1.7-V400M mutant channels from a family with carbamazepine-responsive
      inherited erythromelalgia. Here we show that structural modelling and
      thermodynamic analysis predict pharmacoresponsiveness of another mutant channel
      (S241T) that is located 159 amino acids distant from V400M. Structural modelling
      reveals that Na(v)1.7-S241T is ~2.4 A apart from V400M in the folded channel, and
      thermodynamic analysis demonstrates energetic coupling of V400M and S241T during
      activation. Atomic proximity and energetic coupling are paralleled by
      pharmacological coupling, as carbamazepine (30 MUM) depolarizes S214T activation,
      as previously reported for V400M. Pharmacoresponsiveness of S241T to
      carbamazepine was further evident at a cellular level, where carbamazepine
      normalized the hyperexcitability of dorsal root ganglion neurons expressing
      S241T. We suggest that this approach might identify variants that confer enhanced
      pharmacoresponsiveness on a variety of channels.

PMID- 23149733
TI  - Room temperature self-assembly of mixed nanoparticles into photonic structures.
AB  - Manufacturing complex composites and structures using incompatible materials is
      central to next-generation technologies. In photonics, silica offers passivity,
      low loss and robustness, making it the ideal material platform for optical
      transport. However, these properties partly stem from the high-temperature
      processing conditions necessary for silica waveguide fabrication, restricting the
      functionalisation of waveguides to robust inorganic dopants. This means for many
      sensor and active device applications, large numbers of materials are excluded.
      These include many organic and carbon systems such as dyes and diamond. Here we
      propose using intermolecular forces to bind nanoparticles together at room
      temperature and demonstrate the room-temperature self-assembly of long microwires
      (length ~7 cm, width ~10 MUm) with and without rhodamine B. Further we report on
      mixed self-assembly of silica and single-photon-emitting nitrogen-vacancy
      containing diamond nanoparticles, opening up a new direction in material science.

PMID- 23149734
TI  - Surface symmetry-breaking and strain effects on orbital occupancy in transition
      metal perovskite epitaxial films.
AB  - The electron occupancy of 3d-orbitals determines the properties of transition
      metal oxides. This can be achieved, for example, through thin-film
      heterostructure engineering of ABO(3) oxides, enabling emerging properties at
      interfaces. Interestingly, epitaxial strain may break the degeneracy of 3d-e(g)
      and t(2g) orbitals, thus favoring a particular orbital filling with consequences
      for functional properties. Here we disclose the effects of symmetry breaking at
      free surfaces of ABO(3) perovskite epitaxial films and show that it can be
      combined with substrate-induced epitaxial strain to tailor at will the electron
      occupancy of in-plane and out-of-plane surface electronic orbitals. We use X-ray
      linear dichroism to monitor the relative contributions of surface, strain and
      atomic terminations to the occupancy of 3z(2)-r(2) and x(2)-y(2) orbitals in
      La(2/3)Sr(1/3)MnO(3) films. These findings open the possibility of an active
      tuning of surface electronic and magnetic properties as well as chemical
      properties (catalytic reactivity, wettability and so on).

PMID- 23149735
TI  - Spectroscopic observation of iodosylarene metalloporphyrin adducts and
      manganese(V)-oxo porphyrin species in a cytochrome P450 analogue.
AB  - Different metalloporphyrin model compounds have been synthesized to study the
      mechanisms of cytochrome P450s with various terminal oxidants, and numerous
      intermediates have been reported. However, the detailed mechanism of the oxygen
      atom transfer from iodosylarene to the substrates remains unclear. Here we report
      the direct ultraviolet-visible spectroscopic observation of the soluble
      iodosylarene-manganese porphyrin adduct following catalytic oxidation using 2,4,6
      tri-tert-butylphenol as the reductant. When the reductant is changed to cis
      stilbene, the rate-determining step also changes. Both the iodosylarene-manganese
      porphyrin adduct and [(porphyrin)Mn(V)=O] species may be simultaneously observed.
      In the absence of reductant, the adduct of iodosylarene with sterically hindered
      [Mn(meso-tetrakis(2,6-dichlorophenyl)porphinato)Cl] is immediately formed, and
      smoothly converted into a high-valent [(porpyrinato)Mn=O]. Electrospray
      ionization mass spectrometry analysis of the reaction further confirms the
      transformation between these species. This study provides an insight into the
      mechanism of oxygen transfer within the haem-containing enzymatic systems.

PMID- 23149736
TI  - Control of exciton spin statistics through spin polarization in organic
      optoelectronic devices.
AB  - Spintronics based on organic semiconductor materials is attractive because of its
      rich fundamental physics and potential for device applications. Manipulating
      spins is obviously important for spintronics, and is usually achieved by using
      magnetic electrodes. Here we show a new approach where spin populations can be
      controlled primarily by energetics rather than kinetics. We find that exciton
      spin statistics can be substantially controlled by spin-polarizing carriers after
      injection using high magnetic fields and low temperatures, where the Zeeman
      energy is comparable with the thermal energy. By using this method, we
      demonstrate that singlet exciton formation can be suppressed by up to 53% in
      organic light-emitting diodes, and the dark conductance of organic photovoltaic
      devices can be increased by up to 45% due to enhanced formation of triplet charge
      transfer states, leading to less recombination to the ground state.

PMID- 23149737
TI  - Observation of a topological crystalline insulator phase and topological phase
      transition in Pb(1-x)Sn(x)Te.
AB  - A topological insulator protected by time-reversal symmetry is realized via spin
      orbit interaction-driven band inversion. The topological phase in the Bi(1
      x)Sb(x) system is due to an odd number of band inversions. A related spin-orbit
      system, the Pb(1-x)Sn(x)Te, has long been known to contain an even number of
      inversions based on band theory. Here we experimentally investigate the
      possibility of a mirror symmetry-protected topological crystalline insulator
      phase in the Pb(1-x)Sn(x)Te class of materials that has been theoretically
      predicted to exist in its end compound SnTe. Our experimental results show that
      at a finite Pb composition above the topological inversion phase transition, the
      surface exhibits even number of spin-polarized Dirac cone states revealing mirror
      protected topological order distinct from that observed in Bi(1-x)Sb(x). Our
      observation of the spin-polarized Dirac surface states in the inverted Pb(1
      x)Sn(x)Te and their absence in the non-inverted compounds related via a
      topological phase transition provide the experimental groundwork for opening the
      research on novel topological order in quantum devices.

PMID- 23149738
TI  - Self-luminescing BRET-FRET near-infrared dots for in vivo lymph-node mapping and
      tumour imaging.
AB  - Strong autofluorescence from living tissues, and the scattering and absorption of
      short-wavelength light in living tissues, significantly reduce sensitivity of in
      vivo fluorescence imaging. These issues can be tackled by using imaging probes
      that emit in the near-infrared wavelength range. Here we describe self
      luminescing near-infrared-emitting nanoparticles employing an energy transfer
      relay that integrates bioluminescence resonance energy transfer and fluorescence
      resonance energy transfer, enabling in vivo near-infrared imaging without
      external light excitation. Nanoparticles were 30-40 nm in diameter, contained no
      toxic metals, exhibited long circulation time and high serum stability, and
      produced strong near-infrared emission. Using these nanoparticles, we
      successfully imaged lymphatic networks and vasculature of xenografted tumours in
      living mice. The self-luminescing feature provided excellent tumour-to-background
      ratio (>100) for imaging very small tumours (2-3 mm in diameter). Our results
      demonstrate that these new nanoparticles are well suited to in vivo imaging
      applications such as lymph-node mapping and cancer imaging.

PMID- 23149739
TI  - Direct writing of electronic devices on graphene oxide by catalytic scanning
      probe lithography.
AB  - Reduction of graphene oxide at the nanoscale is an attractive approach to
      graphene-based electronics. Here we use a platinum-coated atomic force microscope
      tip to locally catalyse the reduction of insulating graphene oxide in the
      presence of hydrogen. Nanoribbons with widths ranging from 20 to 80 nm and
      conductivities of >10(4) S m(-1) are successfully generated, and a field effect
      transistor is produced. The method involves mild operating conditions, and uses
      arbitrary substrates, atmospheric pressure and low temperatures (<=115  degrees
      C).

PMID- 23149741
TI  - Coherent optical wavelength conversion via cavity optomechanics.
AB  - Both classical and quantum systems utilize the interaction of light and matter
      across a wide range of energies. These systems are often not naturally compatible
      with one another and require a means of converting photons of dissimilar
      wavelengths to combine and exploit their different strengths. Here we
      theoretically propose and experimentally demonstrate coherent wavelength
      conversion of optical photons using photon-phonon translation in a cavity
      optomechanical system. For an engineered silicon optomechanical crystal
      nanocavity supporting a 4-GHz localized phonon mode, optical signals in a 1.5 MHz
      bandwidth are coherently converted over a 11.2 THz frequency span between one
      cavity mode at wavelength 1,460 nm and a second cavity mode at 1,545 nm with a
      93% internal (2% external) peak efficiency. The thermal- and quantum-limiting
      noise involved in the conversion process is also analysed, and in terms of an
      equivalent photon number signal level are found to correspond to an internal
      noise level of only 6 and 4 * 10(-3) quanta, respectively.

PMID- 23149740
TI  - Localizing internal friction along the reaction coordinate of protein folding by
      combining ensemble and single-molecule fluorescence spectroscopy.
AB  - Theory, simulations and experimental results have suggested an important role of
      internal friction in the kinetics of protein folding. Recent experiments on
      spectrin domains provided the first evidence for a pronounced contribution of
      internal friction in proteins that fold on the millisecond timescale. However, it
      has remained unclear how this contribution is distributed along the reaction and
      what influence it has on the folding dynamics. Here we use a combination of
      single-molecule Forster resonance energy transfer, nanosecond fluorescence
      correlation spectroscopy, microfluidic mixing and denaturant- and viscosity
      dependent protein-folding kinetics to probe internal friction in the unfolded
      state and at the early and late transition states of slow- and fast-folding
      spectrin domains. We find that the internal friction affecting the folding rates
      of spectrin domains is highly localized to the early transition state, suggesting
      an important role of rather specific interactions in the rate-limiting
      conformational changes.

PMID- 23149743
TI  - Dual-polarity plasmonic metalens for visible light.
AB  - Surface topography and refractive index profile dictate the deterministic
      functionality of a lens. The polarity of most lenses reported so far, that is,
      either positive (convex) or negative (concave), depends on the curvatures of the
      interfaces. Here we experimentally demonstrate a counter-intuitive dual-polarity
      flat lens based on helicity-dependent phase discontinuities for circularly
      polarized light. Specifically, by controlling the helicity of the input light,
      the positive and negative polarity are interchangeable in one identical flat
      lens. Helicity-controllable real and virtual focal planes, as well as magnified
      and demagnified imaging, are observed on the same plasmonic lens at visible and
      near-infrared wavelengths. The plasmonic metalens with dual polarity may empower
      advanced research and applications in helicity-dependent focusing and imaging
      devices, angular-momentum-based quantum information processing and integrated
      nano-optoelectronics.

PMID- 23149742
TI  - The metastasis-promoting S100A4 protein confers neuroprotection in brain injury.
AB  - Identification of novel pro-survival factors in the brain is paramount for
      developing neuroprotective therapies. The multifunctional S100 family proteins
      have important roles in many human diseases and are also upregulated by brain
      injury. However, S100 functions in the nervous system remain unclear. Here we
      show that the S100A4 protein, mostly studied in cancer, is overexpressed in the
      damaged human and rodent brain and released from stressed astrocytes. Genetic
      deletion of S100A4 exacerbates neuronal loss after brain trauma or
      excitotoxicity, increasing oxidative cell damage and downregulating the
      neuroprotective protein metallothionein I+II. We identify two neurotrophic motifs
      in S100A4 and show that these motifs are neuroprotective in animal models of
      brain trauma. Finally, we find that S100A4 rescues neurons via the Janus
      kinase/STAT pathway and, partially, the interleukin-10 receptor. Our data
      introduce S100A4 as a therapeutic target in neurodegeneration, and raise the
      entire S100 family as a potentially important factor in central nervous system
      injury.

PMID- 23149744
TI  - The Hedgehog signalling pathway regulates autophagy.
AB  - Autophagy is a highly conserved degradative process that removes damaged or
      unnecessary proteins and organelles, and recycles cytoplasmic contents during
      starvation. Autophagy is essential in physiological processes such as embryonic
      development but how autophagy is regulated by canonical developmental pathways is
      unclear. Here we show that the Hedgehog signalling pathway inhibits autophagosome
      synthesis, both in basal and in autophagy-induced conditions. This mechanism is
      conserved in mammalian cells and in Drosophila, and requires the orthologous
      transcription factors Gli2 and Ci, respectively. Furthermore, we identify that
      activation of the Hedgehog pathway reduces PERK levels, concomitant with a
      decrease in phosphorylation of the translation initiation factor eukaryotic
      initiation factor 2alpha, suggesting a novel target of this pathway and providing
      a possible link between Hedgehog signalling and autophagy.

PMID- 23149745
TI  - Tracking lithium transport and electrochemical reactions in nanoparticles.
AB  - Expectations for the next generation of lithium batteries include greater energy
      and power densities along with a substantial increase in both calendar and cycle
      life. Developing new materials to meet these goals requires a better
      understanding of how electrodes function by tracking physical and chemical
      changes of active components in a working electrode. Here we develop a new,
      simple in-situ electrochemical cell for the transmission electron microscope and
      use it to track lithium transport and conversion in FeF(2) nanoparticles by
      nanoscale imaging, diffraction and spectroscopy. In this system, lithium
      conversion is initiated at the surface, sweeping rapidly across the FeF(2)
      particles, followed by a gradual phase transformation in the bulk, resulting in 1
      3 nm iron crystallites mixed with amorphous LiF. The real-time imaging reveals a
      surprisingly fast conversion process in individual particles (complete in a few
      minutes), with a morphological evolution resembling spinodal decomposition. This
      work provides new insights into the inter- and intra-particle lithium transport
      and kinetics of lithium conversion reactions, and may help to pave the way to
      develop high-energy conversion electrodes for lithium-ion batteries.

PMID- 23149747
TI  - Virtual metagenome reconstruction from 16S rRNA gene sequences.
AB  - Microbial ecologists have investigated roles of species richness and diversity in
      a wide variety of ecosystems. Recently, metagenomics have been developed to
      measure functions in ecosystems, but this approach is cost-intensive. Here we
      describe a novel method for the rapid and efficient reconstruction of a virtual
      metagenome in environmental microbial communities without using large-scale
      genomic sequencing. We demonstrate this approach using 16S rRNA gene sequences
      obtained from denaturing gradient gel electrophoresis analysis, mapped to fully
      sequenced genomes, to reconstruct virtual metagenome-like organizations.
      Furthermore, we validate a virtual metagenome using a published metagenome for
      cocoa bean fermentation samples, and show that metagenomes reconstructed from
      biofilm formation samples allow for the study of the gene pool dynamics that are
      necessary for biofilm growth.

PMID- 23149746
TI  - Genome sequences of wild and domestic bactrian camels.
AB  - Bactrian camels serve as an important means of transportation in the cold desert
      regions of China and Mongolia. Here we present a 2.01 Gb draft genome sequence
      from both a wild and a domestic bactrian camel. We estimate the camel genome to
      be 2.38 Gb, containing 20,821 protein-coding genes. Our phylogenomics analysis
      reveals that camels shared common ancestors with other even-toed ungulates about
      55-60 million years ago. Rapidly evolving genes in the camel lineage are
      significantly enriched in metabolic pathways, and these changes may underlie the
      insulin resistance typically observed in these animals. We estimate the genome
      wide heterozygosity rates in both wild and domestic camels to be 1.0 * 10(-3).
      However, genomic regions with significantly lower heterozygosity are found in the
      domestic camel, and olfactory receptors are enriched in these regions. Our
      comparative genomics analyses may also shed light on the genetic basis of the
      camel's remarkable salt tolerance and unusual immune system.

PMID- 23149748
TI  - A monomeric red fluorescent protein with low cytotoxicity.
AB  - Multicolour labelling with fluorescent proteins is frequently used to
      differentially highlight specific structures in living systems. Labelling with
      fusion proteins is particularly demanding and is still problematic with the
      currently available palette of fluorescent proteins that emit in the red range
      due to unsuitable subcellular localization, protein-induced toxicity and low
      levels of labelling efficiency. Here we report a new monomeric red fluorescent
      protein, called FusionRed, which demonstrates both high efficiency in fusions and
      low toxicity in living cells and tissues.

PMID- 23149749
TI  - Hyperlenses and metalenses for far-field super-resolution imaging.
AB  - The resolution of conventional optical lens systems is always hampered by the
      diffraction limit. Recent developments in artificial metamaterials provide new
      avenues to build hyperlenses and metalenses that are able to image beyond the
      diffraction limit. Hyperlenses project super-resolution information to the far
      field through a magnification mechanism, whereas metalenses not only super
      resolve subwavelength details but also enable optical Fourier transforms.
      Recently, there have been numerous designs for hyperlenses and metalenses,
      bringing fresh theoretical and experimental advances, though future directions
      and challenges remain to be overcome.

PMID- 23149750
TI  - Detection and differential diagnosis of colon cancer by a cumulative analysis of
      promoter methylation.
AB  - Alterations in the methylation of promoters of cancer-related genes are promising
      biomarkers for the early detection of disease. Compared with single methylation
      alteration, assessing combined methylation alterations can provide higher
      association with specific cancer. Here we use cationic conjugated polymer-based
      fluorescence resonance energy transfer to quantitatively analyse DNA methylation
      levels of seven colon cancer-related genes in a Chinese population. Through a
      stepwise discriminant analysis and cumulative detection of methylation
      alterations, we acquire high accuracy and sensitivity for colon cancer detection
      (86.3 and 86.7%) and for differential diagnosis (97.5 and 94%). Moreover, we
      identify a correlation between the CpG island methylator phenotype and clinically
      important parameters in patients with colon cancer. The cumulative analysis of
      promoter methylation alterations by the cationic conjugated polymer-based
      fluorescence resonance energy transfer may be useful for the screening and
      differential diagnosis of patients with colon cancer, and for performing clinical
      correlation analyses.

PMID- 23149751
TI  - Orthogonal switching of a single supramolecular complex.
AB  - Orthogonal control over systems represents an advantage over mono-functional
      switches as both the nature and order of distinctly different stimuli manifest
      themselves in a wide array of outcomes. Host-guest complexes with multiple,
      simultaneously bound guests offer unique opportunities to address a set of 'on'
      and 'off' states accessible on demand. Here we report cucurbit[8]uril-mediated
      host-guest heteroternary complexes constructed with both redox- and light
      responsive guests in a single, supramolecular entity. The complex responds to
      orthogonal stimuli in a controlled, reversible manner generating a
      multifunctional switch between a 'closed' heteroternary complex, a redox-driven
      'closed' homoternary complex and a photo-driven 'open' uncomplexed state. We
      exploit both photochemical and electrochemical control over the supramolecular
      coding system and its surface wettability to demonstrate the system's complexity,
      which could be readily visualized on a macroscopic level, thus offering new
      opportunities in the construction of memory devices.

PMID- 23149752
TI  - Declining rates of tobacco use in the Japanese medical profession, 1965-2009.
AB  - BACKGROUND: Although there has been a downward trend in smoking rates among
      medical doctors in recent years, rates have been higher among Japanese doctors
      when compared internationally. METHODS: We extensively reviewed all published
      English- and Japanese-language articles that reported the smoking rates of
      Japanese doctors. RESULTS: A total of 36 articles were examined, most of which
      had been conducted as postal surveys, usually by a national, prefectural, or
      local medical association. Sample sizes ranged from 17 to 11 773, and response
      rates ranged from 33% to 91%. National surveys conducted between 1965 and 2009
      suggest that there has been a statistically significant (P < 0.0001) decline in
      smoking rates among Japanese doctors (from around 68% to 16% among males and from
      19% to 5% among females). CONCLUSIONS: Overall, the published data reveal a
      significant decline in smoking rates among Japanese doctors since 1965,
      especially among men. Although less than one-fifth of Japanese male doctors now
      smoke, more work needs to be done in tobacco control to help further reduce the
      burden of smoking, especially in medical schools.

PMID- 23149753
TI  - Mutant firefly luciferases with improved specific activity and dATP
      discrimination constructed by yeast cell surface engineering.
AB  - Pyrosequencing system utilizing luciferase is one of the next-generation DNA
      sequencing systems. However, there is a crucial problem with the current
      pyrosequencing system: luciferase cannot discriminate between ATP and dATP
      completely, and dATPalphaS must be used as the dATP analogue. dATPalphaS is
      expensive and has low activity for the enzyme. If luciferase can clearly
      recognize the difference between ATP and dATP, dATP could be used instead of the
      expensive dATPalphaS in the pyrosequencing system. We attempted to prepare a
      novel luciferase with improved specific activity and dATP discrimination with the
      molecular display method. First, we selected two amino acid residues, Ser440 and
      Ser456, as target residues for mutation from the whole sequence of Photinus
      pyralis luciferase; we comprehensively mutated these two amino acids. A mutant
      luciferase library was constructed using yeast cell surface engineering. Through
      three step-wide screenings with individual conditions, we easily and speedily
      isolated three candidate mutants from 1,152 candidates and analyzed the
      properties of these mutants. Consequently, we succeeded in obtaining interesting
      mutant luciferases with improved specific activity and dATP discrimination more
      conveniently than with other methods.

PMID- 23149754
TI  - Construction and expression of sTRAIL-melittin combining enhanced anticancer
      activity with antibacterial activity in Escherichia coli.
AB  - Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), as an anticancer
      protein with tumor-selective apoptotic activity, has been examined for use in
      clinical application. Melittin, an antibacterial peptide isolated from the bee
      Apis mellifera, has shown strong cytotoxicity to both tumor and normal cells. To
      ameliorate the cytotoxicity of melittin on cells and enhance the activity of
      TRAIL on cancer cells, we constructed a novel fusion protein, sTRAIL-melittin,
      containing a small ubiquitin-related modifier (SUMO) tag and expressed this
      fusion protein in Escherichia coli. Data showed that expression of the soluble
      fusion protein with the SUMO tag was approximately 85% of total target protein
      which was much higher than that without the SUMO tag (approximately 10%); sTRAIL
      melittin was easily purified using Ni-NTA affinity chromatography and the tag was
      removed easily using SUMO-specific protease. To assay anticancer activity and
      side effects, methyl thiazolyl tetrazolium, hemolytic, and apoptosis assays were
      employed. Results demonstrated that sTRAIL-melittin had cytotoxic and apoptotic
      activity in K562 leukemia cells and HepG2 liver carcinoma cells, while it had
      only a minimal effect on erythrocytes and normal HEK293 cells. This indicates
      that the cytotoxicity of sTRAIL-melittin in normal cells was low and the
      anticancer activity of the fusion protein in tumor cells was significantly
      enhanced compared with sTRAIL (P<0.01). Furthermore, we found that sTRAIL
      melittin also showed antibacterial activity to Staphylococcus aureus due to the
      presence of the melittin domain. Therefore, TRAIL fused with an antibacterial
      peptide may be a promising novel TRAIL-based anticancer treatment strategy.

PMID- 23149755
TI  - Rational and efficient preparation of a chimeric protein containing a tandem
      dimer of thrombopoietin mimetic peptide fused to human growth hormone in
      Escherichia coli.
AB  - The 14-mer thrombopoietin mimetic peptide (TMP), especially in the form of dimer,
      displayed potent megakaryocytopoiesis activity in vitro. However, it is difficult
      to prepare such short peptide with high bioactivity through gene-engineering
      approaches. In this study, a chimeric protein containing a tandem dimer of TMP
      (dTMP) fused to human growth hormone (hGH), a kind of hematopoietic growth factor
      that activates the same signal pathways as thrombopoietin, was produced in
      Escherichia coli by soluble expression. By rational utilization of the XmnI and
      EcoRV restriction sites, a PCR fragment encoding dTMP-GH was inserted into the
      plasmid vector pMAL-p2X at the position right after Xa factor cleavage site, in
      frame with maltose-binding protein (MBP) gene. Under optimized conditions, a high
      level expression of soluble MBP-dTMP-GH fusion protein was obtained. By
      application of amylose resin chromatography, Xa factor digestion, hydrophobic
      chromatography followed by gel filtration, the dTMP-GH fusion protein was
      separated. Finally, a relatively high yield of dTMP-GH fusion protein with high
      purity (>98%) and without redundant amino acid was achieved, as identified by
      high-performance liquid chromatography, mass spectrometry, and amino acid
      sequencing. The functional assays showed that dTMP-GH could promote the
      proliferation of megakaryoblast cells and maturation of murine megakaryocytes
      derived from bone marrow, in a dose-dependent manner. Moreover, an enhanced
      effect of dTMP-GH on megakaryocytopoiesis was found as compared with equimolar
      concentration of dTMP and rhGH. This work provides a new avenue to generate
      thrombopoietic agents based on TMP.

PMID- 23149756
TI  - Biochemical characterization of a thermostable beta-1,3-xylanase from the
      hyperthermophilic eubacterium, Thermotoga neapolitana strain DSM 4359.
AB  - The biochemical properties of a putative beta-1,3-xylanase from the
      hyperthermophilic eubacterium Thermotoga neapolitana DSM 4359 were determined
      from a recombinant protein (TnXyn26A) expressed in Escherichia coli. This enzyme
      showed specific hydrolytic activity against beta-1,3-xylan and released beta-1,3
      xylobiose and beta-1,3-xylotriose as main products. It displayed maximum activity
      at 85  degrees C during a 10-min incubation, and its activity half-life was 23.9
      h at 85  degrees C. Enzyme activity was stable in the pH range 3-10, with pH 6.5
      being optimal. Enzyme activity was significantly inhibited by the presence of N
      bromosuccinimide (NBS). The insoluble beta-1,3-xylan K m value was 10.35 mg/ml
      and the k cat value was 588.24 s(-1). The observed high thermostability and
      catalytic efficiency of TnXyn26A is both industrially desirable and also aids an
      understanding of the chemistry of its hydrolytic reaction.

PMID- 23149757
TI  - Overcoming recalcitrant transformation and gene manipulation in Pucciniomycotina
      yeasts.
AB  - The red yeasts of the Pucciniomycotina have rarely been transformed with DNA
      molecules. Transformation methods were recently developed for a species of
      Sporobolomyces, based on selection using uracil auxotrophs and plasmids carrying
      the wild-type copies of the URA3 and URA5 genes. However, these plasmids were
      ineffective in the transformation of closely related species. Using the genome
      sequenced strain of Rhodotorula graminis as a starting point, the URA3 and URA5
      genes were cloned and tested for the transformation ability into different
      Pucciniomycotina species by biolistic and Agrobacterium-mediated transformations.
      Transformation success depended on the red yeast species and the origin of the
      URA3 or URA5 genes, which may be related to the high G + C DNA content found in
      several species. A new vector was generated to confer resistance to
      nourseothricin, using a native promoter from R. graminis and the naturally high G
      + C nourseothricin acetyltransferease gene. This provides a second selectable
      marker in these species. Targeted gene disruption was tested in Sporobolomyces
      sp. IAM 13481 using different lengths of homologous DNA with biolistic and
      Agrobacterium transformation methods. Both DNA delivery methods were effective
      for targeted replacement of a gene required for carotenoid pigment biosynthesis.
      The constructs also triggered transgene silencing. These developments open the
      way to identify and manipulate gene functions in a large group of basidiomycete
      fungi.

PMID- 23149758
TI  - Inhibition of hydrogen sulfide, methane, and total gas production and sulfate
      reducing bacteria in in vitro swine manure by tannins, with focus on condensed
      quebracho tannins.
AB  - Management practices from large-scale swine production facilities have resulted
      in the increased collection and storage of manure for off-season fertilization
      use. Odor and emissions produced during storage have increased the tension among
      rural neighbors and among urban and rural residents. Production of these
      compounds from stored manure is the result of microbial activity of the anaerobic
      bacteria populations during storage. In the current study, the inhibitory effects
      of condensed quebracho tannins on in vitro swine manure for reduction of
      microbial activity and reduced production of gaseous emissions, including the
      toxic odorant hydrogen sulfide produced by sulfate-reducing bacteria (SRB), was
      examined. Swine manure was collected from a local swine facility, diluted in
      anaerobic buffer, and mixed with 1 % w/v fresh feces. This slurry was combined
      with quebracho tannins, and total gas and hydrogen sulfide production was
      monitored over time. Aliquots were removed periodically for isolation of DNA to
      measure the SRB populations using quantitative PCR. Addition of tannins reduced
      overall gas, hydrogen sulfide, and methane production by greater than 90 % after
      7 days of treatment and continued to at least 28 days. SRB population was also
      significantly decreased by tannin addition. qRT-PCR of 16S rDNA bacteria genes
      showed that the total bacterial population was also decreased in these
      incubations. These results indicate that the tannins elicited a collective effect
      on the bacterial population and also suggest a reduction in the population of
      methanogenic microorganisms as demonstrated by reduced methane production in
      these experiments. Such a generalized effect could be extrapolated to a reduction
      in other odor-associated emissions during manure storage. 

PMID- 23149759
TI  - An Internet-based tailored hearing protection intervention for firefighters:
      development process and users' feedback.
AB  - BACKGROUND: Noise-induced hearing loss is a significant occupational injury for
      firefighters exposed to intermittent noise on the job. It is important to educate
      firefighters about using hearing protection devices whenever they are exposed to
      loud noise. Computer technology is a relatively new health education approach and
      can be useful for tailoring specific aspects of behavioral change training. The
      purpose of this study is to present the development process of an Internet-based
      tailored intervention program and to assess its efficacy. METHOD: The
      intervention programs were implemented for 372 firefighters (mean age = 44 years,
      Caucasian = 82%, male = 95%) in three states (California, Illinois, and Indiana).
      The efficacy was assessed from firefighters' feedback through an Internet-based
      survey. RESULTS: A multimedia Internet-based training program was developed
      through (a) determining program content and writing scripts, (b) developing
      decision-making algorithms for tailoring, (c) graphic design and audio and video
      productions, (d) creating computer software and a database, and (e)
      postproduction quality control and pilot testing. Participant feedback regarding
      the training has been very positive. Participants reported that they liked
      completing the training via computer (83%) and also that the Internet-based
      training program was well organized (97%), easy to use (97%), and effective (98%)
      and held their interest (79%). Almost all (95%) would recommend this Internet
      training program to other firefighters. CONCLUSION: Interactive multimedia
      computer technology using the Internet was a feasible mode of delivery for a
      hearing protection intervention among firefighters. Participants' favorable
      feedback strongly supports the continued utilization of this approach for
      designing and developing interventions to promote healthy behaviors.

PMID- 23149760
TI  - Assessing the quantum mechanical level of theory for prediction of linear and
      nonlinear optical properties of push-pull organic molecules.
AB  - In this paper, we assessed the quantum mechanical level of theory for prediction
      of linear and nonlinear optical (NLO) properties of push-pull organic molecules.
      The electric dipole moment (MU), mean polarizability ([Symbol: see
      text]alpha[Symbol: see text]) and total static first hyperpolarizability (betat)
      were calculated for a set of benzene, styrene, biphenyl and stilbene derivatives
      using HF, MP2 and DFT (31 different functionals) levels and over 71 distinct
      basis sets. In addition, we propose two new basis sets, NLO-V and aNLO-V, for NLO
      properties calculations. As the main outcomes it is shown that long-range
      corrected DFT functionals such as M062X, omegaB97, cam-B3LYP, LC-BLYP and LC
      omegaPBE work satisfactorily for NLO properties when appropriate basis sets such
      as those proposed here (NLO-V or aNLO-V) are used. For most molecules with beta
      ranging from 0 to 190 esu, the average absolute deviation was 13.2 esu for NLO-V
      basis sets, compared to 27.2 esu for the standard 6-31 G(2d) basis set.
      Therefore, we conclude that the new basis sets proposed here (NLO-V and aNLO-V),
      together with the cam-B3LYP functional, make an affordable calculation scheme to
      predict NLO properties of large organic molecules.

PMID- 23149761
TI  - Aqueous solvent effects on the conformational space of tryptamine. Structural and
      electronic analysis.
AB  - The TRA (3-[2-aminoethyl]indole) is an important neurotransmitter with a close
      structural and chemical similarity to the neurotransmitter serotonin (5
      hydroxytryptamine), and to melatonin (5-methoxy-N-acetyltryptamine), which plays
      a key role in daily human behavior. Moreover, TRA, and other indolic compounds
      are very efficient antioxidants. In this work the conformational space of TRA was
      scanned in aqueous solution, simulating the solvent by the polarizable continuum
      model. Geometry optimizations were performed at B3LYP/6-31+G** level. Electronic
      distributions were analyzed at a better calculation level, thus improving the
      basis set (6-311++G**). A topological study based on Bader's theory (atoms in
      molecules) and natural bond orbital (NBO) framework was performed. Structural
      changes found in solution were related with charge delocalization mechanisms,
      which explained the changes in the conformational relative population in aqueous
      phase. Solvent effects on molecular electrostatic potential (MEPs) were also
      quantified and rationalized through charge delocalization mechanisms, thus
      connecting changes in MEPs with changes in structure, bond polarization, orbital
      bonding populations, natural charges, and bond topological properties. Moreover,
      polarizabilities and dipolar moments were calculated. All conformers were taken
      into account. Our results are the first prediction of TRA polarizabilities. The
      results reported contribute to the understanding of the structure, stability and
      reactivity of TRA and other indole derivatives.

PMID- 23149762
TI  - Specificities of boron disubstituted sumanenes.
AB  - In this article we focused on computational research of sumanenes disubstituted
      by boron where the two carbon atoms are substituted by two boron atoms.
      Disubstitution of rim carbon atoms with boron atoms significantly affected the
      geometry of the bowl. The main stability factors were used to determine the
      stability of isomers. The most stable, the shallowest and the deepest isomers
      were subjected to further study of NMR parameters, chemical shielding and NICS,
      aromaticity, bowl to bowl inversion barrier and NBO/NPA analysis. The
      introduction of boron atoms significantly affected the above parameters, changing
      the aromatic nature of rings, reducing bowl to bowl inversion barrier and
      produced charge transfer. The NICS are correlated with bowl depth having the
      result that the function of the fourth degree of bowl depth does not only
      correlate well to the bowl to bowl inversion barrier with bowl depth, but also
      finely correlates the change of the NICS and NICSzz with bowl depth.

PMID- 23149763
TI  - Can cyclic HIV protease inhibitors bind in a non-preferred form? An ab initio,
      DFT and MM-PB(GB)SA study.
AB  - X-ray crystallography studies have identified that most cyclic inhibitors of HIV
      protease (including cyclic ureas) bind in a symmetric manner, however some cyclic
      inhibitors, such as cyclic sulfamides, bind in a non-symmetric manner. This
      raises the question as to whether it is possible for cyclic sulfamides to bind
      symmetrically and conversely for cyclic ureas to bind non-symmetrically. Herein
      we report an analysis of the conformational preference of cyclic ureas and
      sulfamides both free in solution and bound to HIV protease, including an
      investigation of the effect of branching. Quantum chemical calculations (B3LYP,
      M06-2X, MP2, CCSD(T)) predict the cyclic urea to prefer a symmetric conformation
      in solution, with a large activation barrier towards inter-conversion to the non
      symmetric conformation. This differs from the cyclic sulfamides, which marginally
      prefer a non-symmetric conformation with a much smaller barrier to inter
      conversion making it more likely for a non-preferred conformation to be observed.
      It is predicted that the cyclic scaffold itself favours a symmetric form, while
      branching induces a preference for a non-symmetric form. MD simulations on the
      free inhibitors identified inter-conversion with the cyclic sulfamides but not
      the cyclic ureas, in support of the quantum chemical results. MM-PB(GB)SA
      calculations on the cyclic inhibitors bound to HIV protease corroborate the X-ray
      crystallography studies, identifying the cyclic ureas to bind symmetrically and
      the cyclic sulfamides in a non-symmetrical manner. While the non-preferred form
      of the sulfamide may well be present as a free molecule in solution, our results
      suggest that it is unlikely to bind to HIV protease in a symmetric manner.

PMID- 23149764
TI  - Theoretical study on the encapsulation of Pd3-based transition metal clusters
      inside boron nitride nanotubes.
AB  - Chemical functionalization of the boron nitride nanotube (BNNT) allows a wider
      flexibility in engineering its electronic and magnetic properties as well as
      chemical reactivity, thus making it have potential applications in many fields.
      In the present work, the encapsulation of 13 different Pd(3)M (M = Sc, Ti, V, Cr,
      Mn, Fe, Co, Ni, Cu, Zn, Pd, Pt, and Au) clusters inside the (10, 0) BNNT has been
      studied by performing comprehensive density functional theory (DFT) calculations.
      Particular attention is paid to searching for the stable configurations,
      calculating the corresponding binding energies, and evaluating the effects of the
      encapsulation of Pd(3)M cluster on the electronic and magnetic properties of
      BNNT. The results indicate that all the studied Pd(3)M clusters can be stably
      encapsulated inside the (10, 0) BNNT, with binding energies ranging from -0.96
      (for Pd(3)Sc) to -5.31 eV (for Pd(3)V). Moreover, due to a certain amount of
      charge transfer from Pd(3)M clusters to BNNT, certain impurity states are induced
      within the band gap of pristine BNNT, leading to the reduction of the band gap in
      various ways. Most Pd(3)M@BNNT nanocomposites exhibit nonzero magnetic moments,
      which mainly originate from the contribution of the Pd(3)M clusters. In
      particular, the adsorption of O(2) molecule on BNNT is greatly enhanced due to
      Pd(3)M encapsulation. The elongation of O-O bonds of the adsorbed O(2) molecules
      indicates that Pd(3)M@BNNT could be used to fabricate the oxidative catalysis.

PMID- 23149765
TI  - Expression of connexin 30 and connexin 32 in hippocampus of rat during
      epileptogenesis in a kindling model of epilepsy.
AB  - OBJECTIVE: Understanding the molecular and cellular mechanisms underlying
      epileptogenesis yields new insights into potential therapies that may ultimately
      prevent epilepsy. Gap junctions (GJs) create direct intercellular conduits
      between adjacent cells and are formed by hexameric protein subunits called
      connexins (Cxs). Changes in the expression of Cxs affect GJ communication and
      thereby could modulate the dissemination of electrical discharges. The
      hippocampus is one of the main regions involved in epileptogenesis and has a wide
      network of GJs between different cell types where Cx30 is expressed in astrocytes
      and Cx32 exists in neurons and oligodendrocytes. In the present study, we
      evaluated the changes of Cx30 and Cx32 expression in rat hippocampus during
      kindling epileptogenesis. METHODS: Rats were stereotaxically implanted with
      stimulating and recording electrodes in the basolateral amygdala, which was
      electrically stimulated once daily at afterdischarge threshold. Expression of
      Cx30 and Cx32, at both the mRNA and protein levels, was measured in the
      hippocampus at the beginning, in the middle (after acquisition of focal
      seizures), and at the end (after establishment of generalized seizures) of the
      kindling process, by real-time PCR and Western blot. RESULTS: Cx30 mRNA
      expression was upregulated at the beginning of kindling and after acquisition of
      focal seizures. Then it was downregulated when the animals acquired generalized
      seizures. Overexpression of Cx30 mRNA at the start of kindling was consistent
      with the respective initial protein increase. Thereafter, no change was found in
      protein abundance during kindling. Regarding Cx32, mRNA expression decreased
      after acquisition of generalized seizures and no other significant change was
      detected in mRNA and protein abundance during kindling. CONCLUSION: We speculate
      that Cx32 GJ communication in the hippocampus does not contribute to kindling
      epileptogenesis. The Cx30 astrocytic network localized to perivascular regions in
      the hippocampus is, however, overexpressed at the initiation of kindling to clear
      excitotoxic molecules from the milieu.

PMID- 23149766
TI  - [Anorectal diagnostics for proctological diseases].
AB  - The majority of proctological diseases can be defined by a structured evaluation
      of the symptoms and a physical examination. Magnetic resonance imaging (MRI) and
      anal endosonography can detect complex anal fistulas with a high accuracy but MRI
      should be preferred because of its objective visualization. Functional anorectal
      disorders are multifactorial and show morphological and functional irregularities
      in different compartments of the pelvic floor which is why MR defecography is now
      one of the most important methods in diagnostic algorithms. Interpreting the
      results of anal endosonography, anal manometry and neurophysiological testing is
      highly demanding because of large interindividual variability. Scores are used
      for objective measurement of symptom severity and quality of life. In clinical
      practice, well validated scores evaluated in large patient groups with
      predetermined circumstances are needed. Bringing together morphological results
      with scores based on subjective perception is required to optimize diagnostics
      and therapy evaluation in proctology.

PMID- 23149767
TI  - [Open transosseous reconstruction of the rotator cuff: clinical outcome,
      influencing factors and complications].
AB  - BACKGROUND: Open transosseous rotator cuff reconstruction (RCR) still plays a
      prominent role in current treatment of rotator cuff tears. This study aimed to
      examine mid-term and long-term results of clinical outcome, determine influencing
      factors and analyze complications. PATIENTS: This retrospective cohort study
      included 104 Patients following standardized open transosseous RCR. After a mean
      follow-up period of 38.3 months (range 12-71 months) 88 Patients (89 shoulders)
      were available for examination. The mean age of Patients at surgery was 57.1
      years (range 29-83 years). Standardized clinical examination included sonography
      and assessment of the absolute, relative and intra-individual constant scores
      (CS(abs), CS(rel), CS(intra)), Oxford shoulder score (OSS), American shoulder and
      elbow surgeons' score (ASESS) and single assessment numeric evaluation score
      (SANES). The level of significance for analysis of variance (ANOVA) was set at p
      < 0.05 (95% confidence interval). RESULTS: Mean values and standard deviations
      (sigma) were: CS(abs) = 71 points (sigma: 20.3), CS(rel) = 76 points (sigma:
      20.7), CS(intra) = 86 % (sigma: 19.5), OSS(mod) = 77 points (sigma: 20.6), ASESS
      = 73 points (sigma: 23.3) and SANES = 72 % (sigma: 22.0). Clinical results were
      superior when the complaints were initiated by trauma (p < 0.05). Patients with
      massive tears showed inferior results relative to all outcome measures (p <
      0.05). Concomitant pathologies even without surgical relevance were associated
      with inferior outcome (p < 0.05). The factors surgeon, suture material and
      acromioplasty did not exert a significant influence. Revision surgery was
      required in 12 out of 89 (13.5 %) cases and re-ruptures occurred in 19.1%.
      CONCLUSIONS: Objective and subjective clinical results following open
      transosseous RCR were comparable to those of previously described open and
      arthroscopic techniques. Results were superior when the complaints were initiated
      by trauma. Massive tears and concomitant pathologies even without surgical
      relevance were associated with inferior clinical outcome. Open or arthroscopic
      acromioplasty did not add further benefits. A standardized operative procedure
      led to reproducible results irrespective of the factor surgeon.

PMID- 23149768
TI  - [Branch-duct IPMN: underestimated risk of malignancy].

PMID- 23149769
TI  - Design and study of ultrasound-based automatic patient movement monitoring device
      for quantifying the intrafraction motion during teletherapy treatment.
AB  - The aim of the present study is to fabricate indigenously ultrasonic-based
      automatic patient's movement monitoring device (UPMMD) that immediately halts
      teletherapy treatment if a patient moves, claiming accurate field treatment. The
      device consists of circuit board, magnetic attachment device, LED indicator,
      speaker, and ultrasonic emitter and receiver, which are placed on either side of
      the treatment table. The ultrasonic emitter produces the ultrasound waves and the
      receiver accepts the signal from the patient. When the patient moves, the
      receiver activates the circuit, an audible warning sound will be produced in the
      treatment console room alerting the technologist to stop treatment.
      Simultaneously, the electrical circuit to the teletherapy machine will be
      interrupted and radiation will be halted. The device and alarm system can detect
      patient movements with a sensitivity of about 1 mm. Our results indicate that, in
      spite of its low-cost, low-power, high-precision, nonintrusive, light weight,
      reusable and simplicity features, UPMMD is highly sensitive and offers accurate
      measurements. Furthermore, UPMMD is patient-friendly and requires minimal user
      training. This study revealed that the device can prevent the patient's normal
      tissues from unnecessary radiation exposure, and also it is helpful to deliver
      the radiation to the correct tumor location. Using this alarming system the
      patient can be repositioned after interrupting the treatment machine manually. It
      also enables the technologists to do their work more efficiently.

PMID- 23149770
TI  - Dose variations in tumor volumes and organs at risk during IMRT for head-and-neck
      cancer.
AB  - Many head-and-neck cancer (HNC) patients treated with radiotherapy suffer
      significant anatomical changes due to tumor shrinkage or weight loss. The purpose
      of this study was to assess dose changes over target volumes and organs at risk
      during intensity-modulated radiotherapy for HNC patients. Sixteen HNC IMRT
      patients, all requiring bilateral neck irradiation, were enrolled in the study. A
      CTplan was performed and the initial dose distribution was calculated. During the
      treatment, two subsequent CTs at the 15th (CT15) and 25th (CT25) fractions were
      acquired. The initial plan was calculated on the CT15 and CT25, and dose-volume
      differences related to the CTplan were assessed. For target volumes, mean values
      of near-maximun absorbed dose (D2%) increased at the 25th fraction, and doses
      covering 95% and 98% of volume decreased significantly at the 15th fraction.
      Contralateral and ipsilateral parotid gland mean doses increased by 6.1% (range: 
      5.4, 23.5%) and 4.7% (range: -9.1, 22.3%), respectively, at CT25. The D2% in the
      spinal cord increased by 1.8 Gy at CT15. Mean absorbed dose increases at CT15 and
      CT25 were observed in: the lips, 3.8% and 5.3%; the oral cavity, 3.5% and 2.5%;
      and lower middle neck structure, 1.9% and 1.6%. Anatomical changes during
      treatment of HNC patients affect dose distribution and induce a loss of dose
      coverage to target volumes and an overdosage to critical structures. Appropriate
      organs at risk have to be contoured and monitored in order to know if the initial
      plan remains suitable during the course of the treatment. Reported dosimetric
      data can help to identify patients who could benefit from adaptive radiotherapy.

PMID- 23149771
TI  - Sensitivity analysis of physics and planning SmartArc parameters for single and
      partial arc VMAT planning.
AB  - We investigate the sensitivity of various physics and planning SmartArc
      parameters to generate single and partial arc VMAT plans with equivalent or
      better plan quality as IMRT. Patients previously treated with step-and-shoot IMRT
      for several treatment sites were replanned using SmartArc. These treatment sites
      included head and neck, prostate, lung, and spine. Effect of various physics and
      planning SmartArc parameters, such as continuous vs. binned dose rate, dynamic
      leaf gap, leaf speed, maximum delivery time, number of arcs, and control point
      spacing, were investigated for Elekta Axesse and Synergy linacs. Absolute dose
      distribution was measured by using the ArcCHECK 3D cylindrical diode array. For
      all cases investigated, plan metrics such as conformity indices and dose
      homogeneity indices increased, while plan QA decreased with increasing leaf
      speed. Leaf speed had a significant impact on the segment size for low dose per
      fractionation cases. Constraining leaf motion to a lower speed not only avoids
      tiny large leaf travel and low-dose rate value, but also achieves better PTV
      coverage (defined as the volume receiving prescription dose) with less total MUs.
      Maximum delivery time, the number of arcs, and the spacing of control points all
      had similar effects as the leaf motion constraint on dose rate and segment size.
      The maximum delivery time had a significant effect on the optimization, acting as
      a hard constraint. Increasing the control point spacing from 2 to 6 degrees
      increased the PTV coverage, but reduced the absolute dose gamma passing rate.
      Plans generated using continuous and binned dose rate modes did not show any
      difference in the quality and the delivery for the Elekta machines. Dosimetric
      analysis with a 3D cylindrical QA phantom resulted in 93.6%-99.3% of detectors
      with a gamma index (3%/2 mm) < 1 for all cases.

PMID- 23149772
TI  - Noncoplanar intensity-modulated radiation therapy for young female patients with
      mediastinal lymphoma.
AB  - The purpose of this study is to apply noncoplanar intensity-modulated radiation
      therapy (Nonco_IMRT) to young female patients with mediastinal lymphoma.
      Nonco_IMRT was evaluated through a planning comparison study with coplanar IMRT
      (Co_IMRT) and conventional anteroposterior and posteroanterior fields (AP-PA)
      plans. Co_IMRT was performed with five equally spaced beams starting from a
      gantry angle of 216 degrees . Nonco_IMRT used two noncoplanar beams in the
      sagittal plane to replace the Co_IMRT beams that directly irradiated the breasts.
      Nineteen young female patients were enrolled in the retrospective study. Dose
      coverage of the planning target volume (PTV) and the dose delivered to organs at
      risk (OARs) were analyzed. For all patients, PTV coverage and heart V30 were
      similar between the two IMRT techniques (p > 0.05). Compared to Co_IMRT, the mean
      dose delivered and regions receiving a low radiation dose were significantly
      reduced for bilateral breasts and lungs in Nonco_IMRT (p < 0.05). Breast V5 and
      lung V5 were relatively reduced by 21% and 12%, respectively. Compared with the
      conventional AP-PA plan, Nonco_IMRT had better PTV coverage and OARs sparing,
      except for being larger in V5 to breast and lung. In IMRT for young female
      patients with mediastinal lymphoma, using of Nonco_IMRT significantly reduces the
      radiation dose to the breasts and lungs compared with Co_IMRT, and consequently
      reduces the risk of breast second cancer and pulmonary toxicity. Besides young
      female patients, Nonco_IMRT can also benefit other mediastinal lymphoma patients.

PMID- 23149773
TI  - Comparing post-operative human breast specimen radiograph and MRI in lesion
      margin and volume assessment.
AB  - The purpose of this research is to evaluate the potential for identifying
      malignant breast lesions and their margins on large specimen MRI, in comparison
      to specimen radiography and clinical dynamic contrast enhanced MRI (DCE-MRI).
      Breast specimens were imaged with an MR scanner immediately after surgery, with
      an IRB-approved protocol and with the patients' informed consent. Specimen sizes
      were at least 5 cm in diameter and approximately 1 to 4 cm thick. Coronal and
      axial gradient echo MR images without fat suppression were acquired over the
      whole specimens using a 9.4T animal scanner. Findings on specimen MRI were
      compared with findings on specimen radiograph, and their volumes were compared
      with measurements obtained from clinical DCE-MRI. The results showed that
      invasive ductal carcinoma (IDC) lesions were easily identified using MRI and the
      margins were clearly distinguishable from nearby tissue. However, ductal
      carcinoma in situ (DCIS) lesions were not clearly discernible and were diffused
      with poorly defined margins on MRI. Calcifications associated with DCIS were
      visualized in all specimens on specimen radiograph. There is a strong correlation
      between the maximum diameter of lesions as measured by radiograph and MRI (r =
      0.93), as well as the maximum diameter measured by pathology and radiograph/MRI
      (r>0.75). The volumes of IDC measured on specimen MRI were slightly smaller than
      those measured on DCE-MRI. Imaging of excised human breast lumpectomy specimens
      with high magnetic field MRI provides promising results for improvements in
      lesion identification and margin localization for IDC. However, there are
      technical challenges in visualization of DCIS lesions. Improvements in specimen
      imaging are important, as they will provide additional information to standard
      radiographic analysis.

PMID- 23149774
TI  - Ion recombination correction factors (P(ion)) for Varian TrueBeam high-dose-rate
      therapy beams.
AB  - Ion recombination is approximately corrected for in the Task Group 51 protocol by
      Pion, which is calculated by a two-voltage measurement. This measurement approach
      may be a poor estimate of the true recombination, particularly if Pion is large
      (greater than 1.05). Concern exists that Pion in high-dose-per-pulse beams, such
      as flattening filter free (FFF) beams, may be unacceptably high, rendering the
      two-voltage measurement technique inappropriate. Therefore, Pion was measured for
      flattened beams of 6, 10, 15, and 18 MV and for FFF beams of 6 and 10 MV. The
      values for the FFF beams were verified with 1/V versus 1/Q curves (Jaffe plots).
      Pion was also measured for electron beams of 6, 12, 16, 18, and 20 MeV on a
      traditional accelerator, as well as on the high-dose-rate Varian TrueBeam
      accelerator. The measurements were made at a range of depths and with PTW, NEL,
      and Exradin Farmer-type chambers. Consistent with the increased dose per pulse,
      Pion was higher for FFF beams than for flattening filter beams. However, for all
      beams, measurement locations, and chambers examined, Pion never exceeded 1.018.
      Additionally, Pion was always within 0.3% of the recombination calculated from
      the Jaffe plots. We conclude that ion recombination can be adequately accounted
      for in high-dose-rate FFF beams using Pion determined with the standard two
      voltage technique.

PMID- 23149775
TI  - Evaluation of mechanical accuracy for couch-based tracking system (CBTS).
AB  - This study evaluated the mechanical accuracy of an in-house-developed couch-based
      tracking system (CBTS) according to respiration data. The overall delay time of
      the CBTS was calculated, and the accuracy, reproducibility, and loading effect of
      the CBTS were evaluated according to the sinusoidal waveform and various
      respiratory motion data of real patients with and without a volunteer weighing
      75kg. The root mean square (rms) error of the accuracy, the reproducibility, and
      the sagging measurements were calculated for the three axes (X, Y, and Z
      directions) of the CBTS. The overall delay time of the CBTS was 0.251 sec. The
      accuracy and reproducibility in the Z direction in real patient data were poor,
      as indicated by high rms errors. The results of the loading effect were within
      1.0 mm in all directions. This novel CBTS has the potential for clinical
      application for tumor tracking in radiation therapy.

PMID- 23149776
TI  - Measurement of low-energy backscatter factors using GAFCHROMIC film and OSLDs.
AB  - Some of the lowest voltages used in radiotherapy are termed Grenz and superficial
      X-rays of ~ 20 and ~ 100 kVp, respectively. Dosimetrically, the surface doses
      from these beams are calculated with the use of a free in-air air kerma
      measurement combined with a backscatter factor and the appropriate ratio of mass
      energy absorption coefficients from the measurement material to water.
      Alternative tools to the standard ion chamber for measuring the BSF are
      GAFCHROMIC EBT2 film and optically stimulated luminescent dosimeter (OSLD)
      crystals made from Al2O3. The scope of this project included making three
      different backscatter measurements with an Xstrahl-D3100 X-ray unit on the Grenz
      ray and superficial settings. These measurements were with OSLDs, GAFCHROMIC EBT2
      film, and a PTW ionization chamber. The varied measurement methods allowed for
      intercomparison to determine the accuracy of the results. The ion chamber
      measurement was the least accurate, as expected from previous experimental
      findings. GAFCHROMIC EBT2 film proved to be a useful tool which gave reasonable
      results, and Landauer OSLDs showed good results for smaller field sizes and an
      increasing overresponse with larger fields. The specific backscatter factors for
      this machine demonstrated values about 5% higher than the universal values
      suggested by the AAPM and IPEMB codes of practice for the 100 kVp setting. The 20
      kvp measured data from both techniques showed general agreement with those found
      in the BJR Supplement No. 10, indicating that this unit's Grenz ray spectrum is
      similar to those used in previous experimental work.

PMID- 23149777
TI  - An automated method for comparing motion artifacts in cine four-dimensional
      computed tomography images.
AB  - The aim of this study is to develop an automated method to objectively compare
      motion artifacts in two four-dimensional computed tomography (4D CT) image sets,
      and identify the one that would appear to human observers with fewer or smaller
      artifacts. Our proposed method is based on the difference of the normalized
      correlation coefficients between edge slices at couch transitions, which we
      hypothesize may be a suitable metric to identify motion artifacts. We evaluated
      our method using ten pairs of 4D CT image sets that showed subtle differences in
      artifacts between images in a pair, which were identifiable by human observers.
      One set of 4D CT images was sorted using breathing traces in which our clinically
      implemented 4D CT sorting software miscalculated the respiratory phase, which
      expectedly led to artifacts in the images. The other set of images consisted of
      the same images; however, these were sorted using the same breathing traces but
      with corrected phases. Next we calculated the normalized correlation coefficients
      between edge slices at all couch transitions for all respiratory phases in both
      image sets to evaluate for motion artifacts. For nine image set pairs, our method
      identified the 4D CT sets sorted using the breathing traces with the corrected
      respiratory phase to result in images with fewer or smaller artifacts, whereas
      for one image pair, no difference was noted. Two observers independently assessed
      the accuracy of our method. Both observers identified 9 image sets that were
      sorted using the breathing traces with corrected respiratory phase as having
      fewer or smaller artifacts. In summary, using the 4D CT data of ten pairs of 4D
      CT image sets, we have demonstrated proof of principle that our method is able to
      replicate the results of two human observers in identifying the image set with
      fewer or smaller artifacts.

PMID- 23149778
TI  - Using four-dimensional computed tomography images to optimize the internal target
      volume when using volume-modulated arc therapy to treat moving targets.
AB  - In this work we used 4D dose calculations, which include the effects of shape
      deformations, to investigate an alternative approach to creating the ITV. We
      hypothesized that instead of needing images from all the breathing phases in the
      4D CT dataset to create the outer envelope used for treatment planning, it is
      possible to exclude images from the phases closest to the inhale phase. We used
      4D CT images from 10 patients with lung cancer. For each patient, we drew a gross
      tumor volume on the exhale-phase image and propagated this to the images from
      other phases in the 4D CT dataset using commercial image registration software.
      We created four different ITVs using the N phases closest to the exhale phase
      (where N = 10, 8, 7, 6). For each ITV contour, we created a volume-modulated arc
      therapy plan on the exhale-phase CT and normalized it so that the prescribed dose
      covered at least 95% of the ITV. Each plan was applied to CT images from each CT
      phase (phases 1-10), and the calculated doses were then mapped to the exhale
      phase using deformable registration. The effect of the motion was quantified
      using the dose to 95% of the target on the exhale phase (D95) and tumor control
      probability. For the three-dimensional and 4D dose calculations of the plan where
      N = 10, differences in the D95 value varied from 3% to 14%, with an average
      difference of 7%. For 9 of the 10 patients, the reduction in D95 was less than 5%
      if eight phases were used to create the ITV. For three of the 10 patients, the
      reduction in the D95 was less than 5% if seven phases were used to create the
      ITV. We were unsuccessful in creating a general rule that could be used to create
      the ITV. Some reduction (8/10 phases) was possible for most, but not all, of the
      patients, and the ITV reduction was small.

PMID- 23149779
TI  - Accuracy of lung nodule density on HRCT: analysis by PSF-based image simulation.
AB  - A computed tomography (CT) image simulation technique based on the point spread
      function (PSF) was applied to analyze the accuracy of CT-based clinical
      evaluations of lung nodule density. The PSF of the CT system was measured and
      used to perform the lung nodule image simulation. Then, the simulated image was
      resampled at intervals equal to the pixel size and the slice interval found in
      clinical high-resolution CT (HRCT) images. On those images, the nodule density
      was measured by placing a region of interest (ROI) commonly used for routine
      clinical practice, and comparing the measured value with the true value (a known
      density of object function used in the image simulation). It was quantitatively
      determined that the measured nodule density depended on the nodule diameter and
      the image reconstruction parameters (kernel and slice thickness). In addition,
      the measured density fluctuated, depending on the offset between the nodule
      center and the image voxel center. This fluctuation was reduced by decreasing the
      slice interval (i.e., with the use of overlapping reconstruction), leading to a
      stable density evaluation. Our proposed method of PSF-based image simulation
      accompanied with resampling enables a quantitative analysis of the accuracy of CT
      based evaluations of lung nodule density. These results could potentially reveal
      clinical misreadings in diagnosis, and lead to more accurate and precise density
      evaluations. They would also be of value for determining the optimum scan and
      reconstruction parameters, such as image reconstruction kernels and slice
      thicknesses/intervals.

PMID- 23149780
TI  - MAGAT gel and EBT2 film-based dosimetry for evaluating source plugging-based
      treatment plan in Gamma Knife stereotactic radiosurgery.
AB  - This work illustrates a procedure to assess the overall accuracy associated with
      Gamma Knife treatment planning using plugging. The main role of source plugging
      or blocking is to create dose falloff in the junction between a target and a
      critical structure. We report the use of MAGAT gel dosimeter for verification of
      an experimental treatment plan based on plugging. The polymer gel contained in a
      head-sized glass container simulated all major aspects of the treatment process
      of Gamma Knife radiosurgery. The 3D dose distribution recorded in the gel
      dosimeter was read using a 1.5T MRI scanner. Scanning protocol was: CPMG pulse
      sequence with 8 equidistant echoes, TR = 7 s, echo step = 14 ms, pixel size =
      0.5mm * 0.5mm, and slice thickness of 2 mm. Using a calibration relationship
      between absorbed dose and spin-spin relaxation rate (R2), we converted R2 images
      to dose images. Volumetric dose comparison between treatment planning system
      (TPS) and gel measurement was accomplished using an in-house MATLAB-based
      program. The isodose overlay of the measured and computed dose distribution on
      axial planes was in close agreement. Gamma index analysis of 3D data showed more
      than 94% voxel pass rate for different tolerance criteria of 3%/2 mm, 3%/1 mm and
      2%/2 mm. Film dosimetry with GAFCHROMIC EBT 2 film was also performed to compare
      the results with the calculated TPS dose. Gamma index analysis of film
      measurement for the same tolerance criteria used for gel measurement evaluation
      showed more than 95% voxel pass rate. Verification of gamma plan calculated dose
      on account of shield is not part of acceptance testing of Leksell Gamma Knife
      (LGK). Through this study we accomplished a volumetric comparison of dose
      distributions measured with a polymer gel dosimeter and Leksell GammaPlan (LGP)
      calculations for plans using plugging. We propose gel dosimeter as a quality
      assurance (QA) tool for verification of plug-based planning.

PMID- 23149781
TI  - A comprehensive dosimetric evaluation of using RapidArc volumetric-modulated arc
      therapy for the treatment of early-stage nasopharyngeal carcinoma.
AB  - The purpose of this study was to investigate the potential benefits of using
      triple-arc volumetric-intensity modulated arc radiotherapy (RapidArc (RA)) for
      the treatment of early-stage nasopharyngeal carcinoma (NPC). A comprehensive
      evaluation was performed including plan quality, integral doses, and peripheral
      doses. Twenty cases of stage I or II NPC were selected for this study. Nine-field
      sliding window IMRT, double-arc, and triple-arc RA treatment plans were compared
      with respect to target coverage, dose conformity, critical organ sparing, and
      integral doses. Measurement of peripheral doses was performed using
      thermoluminescent dosimeters in an anthropomorphic phantom. While similar
      conformity and target coverage were achieved by the three types of plans, triple
      arc RA produced better sparing of parotid glands and spinal cord than double-arc
      RA or IMRT. Double-arc RA plans produced slightly inferior parotid sparing and
      dose homogeneity than the other two delivery methods. The monitor units (MU)
      required for triple-arc were about 50% less than those of IMRT plans, while there
      was no significant difference in the required MUs between triple-arc and double
      arc RA plans. The peripheral dose in triple-arc RA was found to be 50% less
      compared to IMRT near abdominal and pelvic region. Triple-arc RA improves both
      the plan quality and treatment efficiency compared with IMRT for the treatment of
      early stage NPC. It has become the preferred choice of treatment delivery method
      for early stage NPC at our center.

PMID- 23149782
TI  - Six degrees of freedom CBCT-based positioning for intracranial targets treated
      with frameless stereotactic radiosurgery.
AB  - Frameless radiosurgery is an attractive alternative to the framed procedure if it
      can be performed with comparable precision in a reasonable time frame. Here, we
      present a positioning approach for frameless radiosurgery based on in-room
      volumetric imaging coupled with an advanced six-degrees-of-freedom (6 DOF) image
      registration technique which avoids use of a bite block. Patient motion is
      restricted with a custom thermoplastic mask. Accurate positioning is achieved by
      registering a cone-beam CT to the planning CT scan and applying all translational
      and rotational shifts using a custom couch mount. System accuracy was initially
      verified on an anthropomorphic phantom. Isocenters of delineated targets in the
      phantom were computed and aligned by our system with an average accuracy of 0.2
      mm, 0.3 mm, and 0.4 mm in the lateral, vertical, and longitudinal directions,
      respectively. The accuracy in the rotational directions was 0.1 degrees , 0.2
      degrees , and 0.1 degrees  in the pitch, roll, and yaw, respectively. An
      additional test was performed using the phantom in which known shifts were
      introduced. Misalignments up to 10 mm and 3 degrees  in all directions/rotations
      were introduced in our phantom and recovered to an ideal alignment within 0.2 mm,
      0.3 mm, and 0.4 mm in the lateral, vertical, and longitudinal directions,
      respectively, and within 0.3 degrees  in any rotational axis. These values are
      less than couch motion precision. Our first 28 patients with 38 targets treated
      over 63 fractions are analyzed in the patient positioning phase of the study.
      Mean error in the shifts predicted by the system were less than 0.5 mm in any
      translational direction and less than 0.3 degrees  in any rotation, as assessed
      by a confirmation CBCT scan. We conclude that accurate and efficient frameless
      radiosurgery positioning is achievable without the need for a bite block by using
      our 6DOF registration method. This system is inexpensive compared to a couch
      based 6 DOF system, improves patient comfort compared to systems that utilize a
      bite block, and is ideal for the treatment of pediatric patients with or without
      general anesthesia, as well as of patients with dental issues. From this study,
      it is clear that only adjusting for 4 DOF may, in some cases, lead to significant
      compromise in PTV coverage. Since performing the additional match with 6 DOF in
      our registration system only adds a relatively short amount of time to the
      overall process, we advocate making the precise match in all cases.

PMID- 23149783
TI  - A Monte Carlo and experimental investigation of the dosimetric behavior of low-
      and medium-perturbation diodes used for entrance in vivo dosimetry in megavoltage
      photon beams.
AB  - Full buildup diodes can cause significant dose perturbation if they are used on
      most or all of radiotherapy fractions. Given the importance of frequent in vivo
      measurements in complex treatments, using thin buildup (low-perturbation) diodes
      instead is gathering interest. However, such diodes are strictly unsuitable for
      high-energy photons; therefore, their use requires evaluation and careful
      measurement of correction factors (CFs). There is little published data on such
      factors for low-perturbation diodes, and none on diode characterization for 9 MV
      X-rays. We report on MCNP4c Monte Carlo models of low-perturbation (EDD5) and
      medium-perturbation (EDP10) diodes, and a comparison of source-to-surface
      distance, field size, temperature, and orientation CFs for cobalt-60 and 9 MV
      beams. Most of the simulation results were within 4% of the measurements. The
      results suggest against the use of the EDD5 in axial angles beyond +/- 50 degrees
      and exceeding the range 0 degrees  to +50 degrees  tilt angle at 9 MV. Outside
      these ranges, although the EDD5 can be used for accurate in vivo dosimetry at 9
      MV, its CF variations were found to be 1.5-7.1 times larger than the EDP10 and,
      therefore, should be applied carefully. Finally, the MCNP diode models are
      sufficiently reliable tools for independent verification of potentially
      inaccurate measurements.

PMID- 23149784
TI  - Patient handling system for carbon ion beam scanning therapy.
AB  - Our institution established a new treatment facility for carbon ion beam scanning
      therapy in 2010. The major advantages of scanning beam treatment compared to the
      passive beam treatment are the following: high dose conformation with less
      excessive dose to the normal tissues, no bolus compensator and patient
      collimator/multi-leaf collimator, better dose efficiency by reducing the number
      of scatters. The new facility was designed to solve several problems encountered
      in the existing facility, at which several thousand patients were treated over
      more than 15 years. Here, we introduce the patient handling system in the new
      treatment facility. The new facility incorporates three main systems, a scanning
      irradiation system (S-IR), treatment planning system (TPS), and patient handling
      system (PTH). The PTH covers a wide range of functions including imaging,
      geometrical/position accuracy including motion management (immobilization,
      robotic arm treatment bed), layout of the treatment room, treatment workflow,
      software, and others. The first clinical trials without respiratory gating have
      been successfully started. The PTH allows a reduction in patient stay in the
      treatment room to as few as 7 min. The PTH plays an important role in carbon ion
      beam scanning therapy at the new institution, particularly in the management of
      patient handling, application of image-guided therapy, and improvement of
      treatment workflow, and thereby allows substantially better treatment at minimum
      cost.

PMID- 23149785
TI  - Measurements of the dose delivered during CT exams using AAPM Task Group Report
      No. 111.
AB  - The computed tomography dose index (CTDI) measured with a 10 cm long pencil
      ionization chamber placed in a 14 cm long PMMA phantom is typically used to
      evaluate the doses delivered during CT procedure. For the new generation of CT
      scanners, the efficiency of this methodology is low because it excludes the
      contribution of radiation scattered beyond the 100 mm range of integration along
      z. The AAPM TG111 Report proposes a new measurement modality using a small volume
      ionization chamber positioned in a phantom long enough to establish dose
      equilibrium at the location of the chamber. In this work, the AAPM report was
      implemented. The minimum scanning length needed to obtain cumulative dose
      equilibrium was evaluated. The equilibrium dose was determined and compared to
      CTDI values informed by the CT scanner, and the dose values were confirmed with
      TLD measurements. The difference between doses measured with TLD and with the
      ionization chamber (IC) was below 1% and the repeatability of the measurements'
      setup was 0.4%. The measurements showed that the scanning lengths needed to reach
      the cumulated dose equilibrium were 450 mm and 380 mm for the central and
      peripheral axes, respectively, which justifies the phantom length. For the
      studied clinical protocols, the doses measured were about 30% higher than those
      informed by the CT scanner. For the new generation of CT systems with wider
      longitudinal detector size or cone-beam technology, the current CTDI measurements
      may no longer be adequate, and the informed CTDI tends to undervalue the dose
      delivered. It is therefore important to evaluate CT radiation doses following the
      AAPM TG111 methodology.

PMID- 23149786
TI  - A light field-based method to adjust rounded leaf end MLC position for split
      shape dose calculation correction in a radiation therapy treatment planning
      system.
AB  - We present an analytical and experimental study of split shape dose calculation
      correction by adjusting the position of the round leaf end position in an
      intensity-modulated radiation therapy treatment planning system. The precise
      light field edge position (Xtang.p ) was derived from 50% of the central axis
      dose created by nominal light field using geometry and mathematical methods. Leaf
      position (Xmlc.p), defined in the treatment planning system for monitor unit
      calculation, could be derived from Xtang.p. Offset (correction) could be obtained
      by the position corresponding to 50% of the central axis dose minus the Xmlc.p
      position. For SSD from 90 cm to 120 cm at 6 MV and 10 MV, the 50% dose position
      was located outside of Xmlc,p in the MLC leaf position range of +8 cm to -8 cm,
      where the offset correction positively increased, whereas the offset correction
      negatively increased when the MLC leaf position was in the range of -12 cm to -8
      cm and +20 cm to +8 cm when the 50% position was located inside Xmlc,p. The
      monitor unit calculation could provide underdosage or overdosage of 7.5% per mm
      without offset correction. Calibration could be performed at a certain SSD to fit
      all SSD offset corrections. With careful measurement and an accurate offset
      correction, it is possible to achieve the dose calculation with 0.5% error for
      the adjusted MLC leaf edge location in the treatment planning system.

PMID- 23149787
TI  - Development and implementation of an EPID-based method for localizing isocenter.
AB  - The aim of this study was to develop a phantom and analysis software that could
      be used to quickly and accurately determine the location of radiation isocenter
      to an accuracy of less than 1 mm using the EPID (Electronic Portal Imaging
      Device). The proposed solution uses a collimator setting of 10 * 10 cm2 to
      acquire EPID images of a new phantom constructed from LEGO blocks. Images from a
      number of gantry and collimator angles are analyzed by automated analysis
      software to determine the position of the jaws and center of the phantom in each
      image. The distance between a chosen jaw and the phantom center is then compared
      to the same distance measured after a 180 degrees  collimator rotation to
      determine if the phantom is centered in the dimension being investigated.
      Repeated tests show that the system is reproducibly independent of the imaging
      session, and calculated offsets of the phantom from radiation isocenter are a
      function of phantom setup only. Accuracy of the algorithm's calculated offsets
      were verified by imaging the LEGO phantom before and after applying the
      calculated offset. These measurements show that the offsets are predicted with an
      accuracy of approximately 0.3 mm, which is on the order of the detector's pitch.
      Comparison with a star-shot analysis yielded agreement of isocenter location
      within 0.5 mm. Additionally, the phantom and software are completely independent
      of linac vendor, and this study presents results from two linac manufacturers. A
      Varian Optical Guidance Platform (OGP) calibration array was also integrated into
      the phantom to allow calibration of the OGP while the phantom is positioned at
      radiation isocenter to reduce setup uncertainty in the calibration. This solution
      offers a quick, objective method to perform isocenter localization as well as
      laser alignment and OGP calibration on a monthly basis.

PMID- 23149788
TI  - Impact of proton beam availability on patient treatment schedule in radiation
      oncology.
AB  - Proton beam therapy offers unique physical properties with potential for reduced
      toxicity and better patient care. There is an increased interest in radiation
      oncology centers to acquire proton therapy capabilities. The operation of a
      proton treatment center is quite different than a photon-based clinic because of
      the more complex technology involved, as well as the single proton beam source
      serving multiple treatment rooms with no backup source available. There is
      limited published data which investigates metrics that can be used to determine
      the performance of a proton facility. The purpose of this study is to evaluate
      performance metrics of Indiana University Cyclotron Operations (IUCO), including
      availability, mean time between failures, and mean time to repair, and to
      determine how changes in these metrics impact patient treatments. We utilized a
      computerized maintenance management system to log all downtime occurrences and
      servicing operations for the facility. These data were then used to calculate the
      availability as well as the mean time between failures and mean time to repair.
      Impact on patient treatments was determined by analyzing delayed and missed
      treatments, which were recorded in an electronic medical record and database
      maintained by the therapists. The availability of the IUCO proton beam has been
      increasing since beginning of operation in 2003 and averaged 96.9% for 2009
      through 2011. The mean time between failures and mean time to repair were also
      determined and correlated with improvements in the maintenance and operating
      procedures of the facility, as well as environmental factors. It was found that
      events less than 15 minutes in duration have minimal impact on treatment delays,
      while events lasting longer than one hour may result in missed treatments. The
      availability of the proton beam was more closely correlated with delayed than
      with missed treatments, demonstrating the utility and limitations of the
      availability metric. In conclusion, we suggest that the availability metric and
      other performance parameters, such as the mean time between failures and the mean
      time to repair, should be used in combination with downtime impact on patient
      treatments in order to adequately evaluate the operational success of a proton
      therapy facility.

PMID- 23149789
TI  - Commissioning kilovoltage cone-beam CT beams in a radiation therapy treatment
      planning system.
AB  - The feasibility of accounting of the dose from kilovoltage cone-beam CT in
      treatment planning has been discussed previously for a single cone-beam CT (CBCT)
      beam from one manufacturer. Modeling the beams and computing the dose from the
      full set of beams produced by a kilovoltage cone-beam CT system requires
      extensive beam data collection and verification, and is the purpose of this work.
      The beams generated by Elekta X-ray volume imaging (XVI) kilovoltage CBCT (kV
      CBCT) system for various cassettes and filters have been modeled in the Philips
      Pinnacle treatment planning system (TPS) and used to compute dose to stack and
      anthropomorphic phantoms. The results were then compared to measurements made
      using thermoluminescent dosimeters (TLDs) and Monte Carlo (MC) simulations. The
      agreement between modeled and measured depth-dose and cross profiles is within 2%
      at depths beyond 1 cm for depth-dose curves, and for regions within the beam
      (excluding penumbra) for cross profiles. The agreements between TPS-calculated
      doses, TLD measurements, and Monte Carlo simulations are generally within 5% in
      the stack phantom and 10% in the anthropomorphic phantom, with larger variations
      observed for some of the measurement/calculation points. Dose computation using
      modeled beams is reasonably accurate, except for regions that include bony
      anatomy. Inclusion of this dose in treatment plans can lead to more accurate dose
      prediction, especially when the doses to organs at risk are of importance.

PMID- 23149790
TI  - Gantry angle determination during arc IMRT: evaluation of a simple EPID-based
      technique and two commercial inclinometers.
AB  - The increasing popularity of intensity-modulated arc therapy (IMAT) treatments
      requires specifically designed linac quality assurance (QA) programs. Gantry
      angle is one of the parameters that has a major effect on the outcome of IMAT
      treatments since dose reconstruction for patient-specific QA relies on the gantry
      angle; therefore, it is essential to ensure its accuracy for correct delivery of
      the prescribed dose. In this study, a simple measurement method and algorithm are
      presented for QA of gantry angle measurements based on integrated EPID images
      acquired at distinct gantry angles and cine EPID images during an entire 360
      degrees  arc. A comprehensive study was carried out to evaluate this method, as
      well as to evaluate two commercially available inclinometers (NG360 and IBA GAS
      supplied in conjunction with popular array dosimeters Delta4 and
      MatriXXEvolution, respectively) by comparing their simultaneous angle measurement
      results with the linac potentiometer readouts at five gantry speeds. In all
      tested measurement systems, the average differences with the reference angle data
      were less than 0.3 degrees  in static mode. In arc mode, at all tested gantry
      speeds the average difference was less than 0.1 degrees  for the IBA GAS and the
      proposed EPID-based method, and 0.6 degrees  for the NG360 after correction for
      the inherent systematic time delay of the inclinometer. The gantry rotation speed
      measured by the three independent systems had an average deviation of about 0.01
      degrees /s from the nominal gantry speed.

PMID- 23149791
TI  - Improving dose calculations on tomotherapy MVCT images.
AB  - The purpose of this investigation was the creation of a new protocol allowing
      more precise dose calculations on megavoltage CT (MVCT) images for tomotherapy,
      both for adaptive and StatRT planning. Daily MVCT images offer, next to
      positioning purposes, the possibility for daily dose check and adaptive planning.
      Dose calculations use the image value to density table (IVDT) to calculate
      physical densities from Hounsfield Units (HUs). These measured HUs change over
      time, leading to a dose calculation error. We noticed dose calculation variations
      due to IVDT changes of: 0.2% dose during a day, up to 1.6% dose from long-term
      variations, and up to 1.5% dose due to technical interventions. An analysis was
      performed applying the general methodology of a calibration problem. A model HU =
      brhoc - 1020 was obtained using a weighted least squares inverse prediction
      method (HU as function of density) taking into account the heteroscedasticity.
      The b parameter is the major variable and depends also on the dose rate (DR). We
      demonstrate the correction for DR variations and the constance of the c
      parameter. Instead of scanning the whole tissue characterization phantom daily,
      we propose a simplified daily protocol: (a) morning airscan-like procedure with
      only two inserts on the table (defining b and thus the IVDT curve), (b) DR
      variations throughout the day can be corrected for using the DR model. A patient
      specific protocol for which two inserts next to the patient are scanned could
      also be used, but results in equal uncertainties and is less practical. Therefore
      we recommend the morning procedure with dose rate variation correction. Applying
      the proposed transformations and the model, the correct IVDT of the moment can be
      reconstructed, with a simple measurement in the morning, and corrected with DR
      changes during the day. This corresponds with a linear mapping in time of the
      proposed IVDT function. The dosimetric variation is hereby reduced from up to 3%
      to 0.4 % for the tested pelvic and head-and-neck cases. In practice, several IVDT
      curves corresponding to "b" values can be entered. The correct IVDT curve of that
      moment can then be chosen from the list. Instead of the two high-density inserts
      on table, any calibrated single density phantom could be used in order to create
      the IVDT curve of the day, but it should have a larger size than the current
      inserts.

PMID- 23149792
TI  - Accuracy and sensitivity of four-dimensional dose calculation to systematic
      motion variability in stereotatic body radiotherapy (SBRT) for lung cancer.
AB  - The dynamic movement of radiation beam in real-time tumor tracking may cause
      overdosing to critical organs surrounding the target. The primary objective of
      this study was to verify the accuracy of the 4D planning module incorporated in
      CyberKnife treatment planning system. The secondary objective was to evaluate the
      error that may occur in the case of a systematic change of motion pattern.
      Measurements were made using a rigid thorax phantom. Target motion was simulated
      with two waveforms (sin and cos4) of different amplitude and frequency. Inversely
      optimized dose distributions were calculated in the CyberKnife treatment planning
      system using the 4D Monte Carlo dose calculation algorithm. Each plan was
      delivered to the phantom assuming (1) reproducible target motion,and (2)
      systematic change of target motion pattern. The accuracy of 4D dose calculation
      algorithm was assessed using GAFCHROMIC EBT2 films based on 5%/3 mm gamma
      criteria. Treatment plans were considered acceptable if the percentage of pixels
      passing the 5%/3 mm gamma criteria was greater than 90%. The mean percentages of
      pixels passing were 95% for the target and 91% for the static off-target
      structure, respectively, with reproducible target motion. When systematic changes
      of the motion pattern were introduced during treatment delivery, the mean
      percentages of pixels passing decreased significantly in the off-target films
      (48%; p < 0.05), but did not change significantly in the target films (92%; p =
      0.324) compared to results of reproducible target motion. These results suggest
      that the accuracy of 4D dose calculation, particularly in off-target stationary
      structure, is strongly tied to the reproducibility of target motion and that the
      solutions of 4D planning do not reflect the clinical nature of nonreproducible
      target motion generally.

PMID- 23149793
TI  - Reference dosimetry using radiochromic film.
AB  - The objectives of this study are to identify and quantify factors that influence
      radiochromic film dose response and to determine whether such films are suitable
      for reference dosimetry. The influence of several parameters that may introduce
      systematic dose errors when performing reference dose measurements were
      investigated. The effect of the film storage temperature was determined by
      comparing the performance of three lots of GAFCHROMIC EBT2 films stored at either
      4oC or room temperature. The effect of high (> 80%) or low (< 20%) relative
      humidity was also determined. Doses measured in optimal conditions with EBT and
      EBT2 films were then compared with an A12 ionization chamber measurement.
      Intensity-modulated radiation therapy quality controls using EBT2 films were also
      performed in reference dose. The results obtained using reference dose
      measurements were compared with those obtained using relative dose measurements.
      Storing the film at 4oC improves the stability of the film over time, but does
      not eliminate the noncatalytic film development, seen as a rise in optical
      density over time in the absence of radiation. Relative humidity variations
      ranging from 80% to 20% have a strong impact on the optical density and could
      introduce dose errors of up to 15% if the humidity were not controlled during the
      film storage period. During the scanning procedure, the film temperature
      influences the optical density that is measured. When controlling for these three
      parameters, the dose differences between EBT or EBT2 and the A12 chamber are
      found to be within +/- 4% (2sigma level) over a dose range of 20-350 cGy. Our
      results also demonstrate the limitation of the Anisotropic Analytical Algorithm
      for dose calculation of highly modulated treatment plans.

PMID- 23149794
TI  - Practical methods for improving dose distributions in Monte Carlo-based IMRT
      planning of lung wall-seated tumors treated with SBRT.
AB  - Current commercially available planning systems with Monte Carlo (MC)-based final
      dose calculation in IMRT planning employ pencil-beam (PB) algorithms in the
      optimization process. Consequently, dose coverage for SBRT lung plans can feature
      cold-spots at the interface between lung and tumor tissue. For lung wall (LW)
      seated tumors, there can also be hot spots within nearby normal organs (example:
      ribs). This study evaluated two different practical approaches to limiting cold
      spots within the target and reducing high doses to surrounding normal organs in
      MC-based IMRT planning of LW-seated tumors. First, "iterative reoptimization",
      where the MC calculation (with PB-based optimization) is initially performed. The
      resultant cold spot is then contoured and used as a simultaneous boost volume.
      The MC-based dose is then recomputed. The second technique uses noncoplanar beam
      angles with limited path through lung tissue. Both techniques were evaluated
      against a conventional coplanar beam approach with a single MC calculation. In
      all techniques the prescription dose was normalized to cover 95% of the PTV.
      Fifteen SBRT lung cases with LW-seated tumors were planned. The results from
      iterative reoptimization showed that conformity index (CI) and/or PTV dose
      uniformity (UPTV) improved in 12/15 plans. Average improvement was 13%, and 24%,
      respectively. Nonimproved plans had PTVs near the skin, trachea, and/or very
      small lung involvement. The maximum dose to 1cc volume (D1cc) of surrounding OARs
      decreased in 14/15 plans (average 10%). Using noncoplanar beams showed an average
      improvement of 7% in 10/15 cases and 11% in 5/15 cases for CI and UPTV,
      respectively. The D1cc was reduced by an average of 6% in 10/15 cases to
      surrounding OARs. Choice of treatment planning technique did not statistically
      significantly change lung V5. The results showed that the proposed practical
      approaches enhance dose conformity in MC-based IMRT planning of lung tumors
      treated with SBRT, improving target dose coverage and potentially reducing
      toxicities to surrounding normal organs.

PMID- 23149795
TI  - Analysis of the advantage of individual PTVs defined on axial 3D CT and 4D CT
      images for liver cancer.
AB  - The purpose of this study was to compare positional and volumetric differences of
      planning target volumes (PTVs) defined on axial three dimensional CT (3D CT) and
      four dimensional CT (4D CT) for liver cancer. Fourteen patients with liver cancer
      underwent 3D CT and 4D CT simulation scans during free breathing. The tumor
      motion was measured by 4D CT. Three internal target volumes (ITVs) were produced
      based on the clinical target volume from 3DCT (CTV3D): i) A conventional ITV
      (ITVconv) was produced by adding 10 mm in CC direction and 5 mm in LR and and AP
      directions to CTV3D; ii) A specific ITV (ITVspec) was created using a specific
      margin in transaxial direction; iii) ITVvector was produced by adding an
      isotropic margin derived from the individual tumor motion vector. ITV4D was
      defined on the fusion of CTVs on all phases of 4D CT. PTVs were generated by
      adding a 5 mm setup margin to ITVs. The average centroid shifts between PTVs
      derived from 3DCT and PTV4D in left-right (LR), anterior-posterior (AP), and
      cranial-caudal (CC) directions were close to zero. Comparing PTV4D to PTVconv,
      PTVspec, and PTVvector resulted in a decrease in volume size by 33.18% +/-
      12.39%, 24.95% +/- 13.01%, 48.08% +/- 15.32%, respectively. The mean degree of
      inclusions (DI) of PTV4D in PTVconv, and PTV4D in PTVspec, and PTV4D in PTVvector
      was 0.98, 0.97, and 0.99, which showed no significant correlation to tumor motion
      vector (r = -0.470, 0.259, and 0.244; p = 0.090, 0.371, and 0.401). The mean DIs
      of PTVconv in PTV4D, PTVspec in PTV4D, and PTVvector in PTV4D was 0.66, 0.73, and
      0.52. The size of individual PTV from 4D CT is significantly less than that of
      PTVs from 3DCT. The position of targets derived from axial 3DCT images scatters
      around the center of 4D targets randomly. Compared to conventional PTV, the use
      of 3D CT-based PTVs with individual margins cannot significantly reduce normal
      tissues being unnecessarily irradiated, but may contribute to reducing the risk
      of missing targets for tumors with large motion.

PMID- 23149796
TI  - The influence of field size on stopping-power ratios in- and out-of-field:
      quantitative data for the BrainLAB m3 micro-multileaf collimator.
AB  - The objective of this work is to quantify the systematic errors introduced by the
      common assumption of invariant secondary electron spectra with changing field
      sizes, as relevant to stereotactic radiotherapy and other treatment modes
      incorporating small beam segments delivered with a linac-based stereotactic unit.
      The EGSnrc/BEAMnrc Monte Carlo radiation transport code was used to construct a
      dosimetrically-matched model of a Varian 600C linear accelerator with mounted
      BrainLAB micro-multileaf collimator. Stopping-power ratios were calculated for
      field sizes ranging from 6 * 6 mm2 up to the maximum (98 * 98 mm2), and
      differences between these and the reference field were computed. Quantitative
      stopping power data for the BrainLAB micro-multileaf collimator has been
      compiled. Field size dependent differences to reference conditions increase with
      decreasing field size and increasing depth, but remain a fraction of a percent
      for all field sizes studied. However, for dosimetry outside the primary field,
      errors induced by the assumption of invariant electron spectra can be greater
      than 1%, increasing with field size. It is also shown that simplification of the
      Spencer-Attix formulation by ignoring secondary electrons below the cutoff
      kinetic energy applied to the integration results in underestimation of stopping
      power ratios of about 0.3% (and is independent of field size and depth). This
      work is the first to quantify stopping powers from a BrainLAB micro-multileaf
      collimator. Many earlier studies model simplified beams, ignoring collimator
      scatter, which is shown to significantly influence the spectrum. Importantly, we
      have confirmed that the assumption of unchanging electron spectra with varying
      field sizes is justifiable when performing (typical) in-field dosimetry of
      stereotactic fields. Clinicians and physicists undertaking precise out-of-field
      measurements for the purposes of risk estimation, ought to be aware that the more
      pronounced spectral variation results in stopping powers (and hence doses) that
      differ more than for in-field dosimetry.

PMID- 23149797
TI  - The impact of continuously-variable dose rate VMAT on beam stability, MLC
      positioning, and overall plan dosimetry.
AB  - A recent control system update for Elekta linear accelerators includes the
      ability to deliver volumetric-modulated arc therapy (VMAT) with continuously
      variable dose rate (CVDR), rather than a number of fixed binned dose rates (BDR).
      The capacity to select from a larger range of dose rates allows the linac to
      maintain higher gantry speeds, resulting in faster, smoother deliveries. The
      purpose of this study is to investigate two components of CVDR delivery - the
      increase in average dose rate and gantry speed, and a determination of their
      effects on beam stability, MLC positioning, and overall plan dosimetry.
      Initially, ten VMAT plans (5 prostate, 5head and neck) were delivered to a Delta4
      dosimetric phantom using both the BDR and CVDR systems. The plans were found to
      be dosimetrically robust using both delivery methods, although CVDR was observed
      to give higher gamma pass rates at the 2%/2 mm gamma level for prostates (p <
      0.01). For the dual arc head-and-neck plans, CVDR delivery resulted in improved
      pass rates at all gamma levels (2%/2 mm to 4%/4 mm) for individual arc
      verifications (p < 0.01), but gave similar results to BDR when both arcs were
      combined. To investigate the impact of increased gantry speed on MLC positioning,
      a dynamic leaf-tracking tool was developed using the electronic portal imaging
      device (EPID). Comparing the detected MLC positions to those expected from the
      plan, CVDR was observed to result in a larger mean error compared to BDR (0.13 cm
      and 0.06 cm, respectively, p < 0.01). The EPID images were also used to monitor
      beam stability during delivery. It was found that the CVDR deliveries had a lower
      standard deviation of the gun-target (GT) and transverse (AB) profiles (p <
      0.01). This study has determined that CVDR may offer a dosimetric advantage for
      VMAT plans. While the higher gantry speed of CVDR appears to increase deviations
      in MLC positioning, the relative effect on dosimetry is lower than the positive
      impact of a flatter and more stable beam profile.

PMID- 23149798
TI  - Impact of backscattered radiation from the bunker structure on EPID dosimetry.
AB  - Amorphous silicon electronic portal imaging devices (EPIDs) have been
      investigated and used for dosimetry in radiotherapy for several years. The
      presence of a phosphor scintillator layer in the structure of these EPIDs has
      made them sensitive to low-energy scattered and backscattered radiation. In this
      study, the backscattered radiation from the walls, ceiling, and floor of a linac
      bunker has been investigated as a possible source of inaccuracy in EPID
      dosimetry. EPID images acquired in integrated mode at discrete gantry angles and
      cine images taken during arcs were used with different field setups (18 * 18 and
      10 * 10 cm2 open square fields at 150 and 105 cm source-to-detector distances) to
      compare the EPID response at different gantry angles. A sliding gap and a dynamic
      head-and-neck IMRT field and a square field with a 15 cm thick cylindrical
      phantom in the beam were also investigated using integrated EPID images at
      several gantry angles. The contribution of linac output variations at different
      angles was evaluated using a 2D array of ion chambers. In addition, a portable
      brick wall was moved to different distances from the EPID to check the effect at
      a single angle. The results showed an agreement of within 0.1% between the arc
      mode and gantry-static mode measurements, and the variation of EPID response
      during gantry rotation was about 1% in all measurement conditions.

PMID- 23149800
TI  - Early growth of Mexican-American children: lagging in preliteracy skills but not
      social development.
AB  - Latino toddlers fall behind White peers at 24 months of age in oral language and
      interactive skills with their mothers in English or Spanish. But Latino children
      enter kindergarten with social skills that rival White peers, despite social
      class disparities. We ask whether cognitive trajectories widen during the 24-48
      month period, how these patterns differ for Latinos, especially Mexican
      Americans, and whether similar gaps in social-emotional growth appear. We
      analyzed growth patterns for a nationally representative birth sample (n = 4,690)
      drawn in 2001, estimating levels of change in development from 24 to 48 months of
      age, focusing on Latino subgroups. The mean gap in cognitive processing for
      Mexican-American children, already wide at 24-months of age relative to Whites
      (three-fourths of a standard deviation), remained constant at 48 months. But
      differences in social-emotional status were statistically insignificant at both
      24 and 48 months. Mexican-American mothers were observed to be equally warm and
      supportive relative to White peers during interaction tasks. Yet the former group
      engaged less frequently in cognitive facilitation, oral language, and preliteracy
      activities in the home. Growth in both cognitive and social domains was
      considerably lower in larger families, placing children raised in poor or Spanish
      speaking homes within a large household at greater risk of delays. Pediatricians
      and practitioners must carefully gauge the social-emotional well-being of Latino
      children, in developmental surveillance activities. Growth in cognitive and
      social domains unfolds independently for children of Mexican heritage, even when
      raised in economically poor families. 

PMID- 23149801
TI  - A novel surgical approach for intratracheal administration of bioactive agents in
      a fetal mouse model.
AB  - Prenatal pulmonary delivery of cells, genes or pharmacologic agents could provide
      the basis for new therapeutic strategies for a variety of genetic and acquired
      diseases. Apart from congenital or inherited abnormalities with the requirement
      for long-term expression of the delivered gene, several non-inherited perinatal
      conditions, where short-term gene expression or pharmacological intervention is
      sufficient to achieve therapeutic effects, are considered as potential future
      indications for this kind of approach. Candidate diseases for the application of
      short-term prenatal therapy could be the transient neonatal deficiency of
      surfactant protein B causing neonatal respiratory distress syndrome(1,2) or
      hyperoxic injuries of the neonatal lung(3). Candidate diseases for permanent
      therapeutic correction are Cystic Fibrosis (CF)(4), genetic variants of
      surfactant deficiencies(5) and alpha1-antitrypsin deficiency(6). Generally, an
      important advantage of prenatal gene therapy is the ability to start therapeutic
      intervention early in development, at or even prior to clinical manifestations in
      the patient, thus preventing irreparable damage to the individual. In addition,
      fetal organs have an increased cell proliferation rate as compared to adult
      organs, which could allow a more efficient gene or stem cell transfer into the
      fetus. Furthermore, in utero gene delivery is performed when the individual's
      immune system is not completely mature. Therefore, transplantation of
      heterologous cells or supplementation of a non-functional or absent protein with
      a correct version should not cause immune sensitization to the cell, vector or
      transgene product, which has recently been proven to be the case with both
      cellular and genetic therapies(7). In the present study, we investigated the
      potential to directly target the fetal trachea in a mouse model. This procedure
      is in use in larger animal models such as rabbits and sheep(8), and even in a
      clinical setting(9), but has to date not been performed before in a mouse model.
      When studying the potential of fetal gene therapy for genetic diseases such as
      CF, the mouse model is very useful as a first proof-of-concept because of the
      wide availability of different transgenic mouse strains, the well documented
      embryogenesis and fetal development, less stringent ethical regulations, short
      gestation and the large litter size. Different access routes have been described
      to target the fetal rodent lung, including intra-amniotic injection(10-12),
      (ultrasound-guided) intrapulmonary injection(13,14) and intravenous
      administration into the yolk sac vessels(15,16) or umbilical vein(17). Our novel
      surgical procedure enables researchers to inject the agent of choice directly
      into the fetal mouse trachea which allows for a more efficient delivery to the
      airways than existing techniques(18).

PMID- 23149802
TI  - Diagnostic workup for diffuse parenchymal lung disease: schematic flowchart,
      literature review, and pitfalls.
AB  - PURPOSE: The term diffuse parenchymal lung disease (DPLD) refers to a group of
      disorders affecting the lung parenchyma that can be categorized into those of
      known and those of unknown etiology. Early diagnosis is important since some
      forms of DPLD are characterized by a rapid progression to respiratory failure.
      Notwithstanding the fact that recently guidelines have been published, some
      issues concerning the practical evaluation of a patient with suspected DPLD
      remain unclear. METHODS: In this article we propose a practical approach to the
      diagnosis and differentiation of DPLD. Moreover, a critical appraisal is provided
      based on the current literature and frequent pitfalls are highlighted.
      CONCLUSION: we propose a practical workup, but in spite of increasing evidence
      concerning the diagnosis of DPLD, further studies will be needed to clarify
      several issues for efficient investigation of newly diagnosed patients with DPLD.

PMID- 23149803
TI  - Mortality, asthma, smoking and acute chest syndrome in young adults with sickle
      cell disease.
AB  - PURPOSE: Sickle cell disease (SCD) patients with asthma have an increased risk of
      death. Acute chest syndrome (ACS) is a major cause of mortality in patients with
      SCD, and ACS may be more common in SCD patients who smoke. The purpose of this
      study was to test the hypothesis that mortality in young adults with SCD would be
      greater than that of controls during a 10-year period and to determine whether
      asthma, reduced lung function, ACS episodes, and/or smoking predicted mortality
      during the follow-up period. METHODS: The outcomes during a 10-year period were
      ascertained of SCD patients and race-matched controls who had taken part in a
      pulmonary function study when they were between age 19 and 27 years. Smoking and
      asthma status and whether they had had ACS episodes were determined, and lung
      function was measured at the initial assessment. RESULTS: Seventy-five subjects
      with SCD were followed for 683 patient years. There were 11 deaths with a
      mortality rate of 1.6 deaths per 100 patient years, which was higher than that of
      the controls; one death in 47 controls was observed for 469 patient years with a
      mortality rate of 0.2 per 100 patient years (p = 0.03). There were no significant
      associations of body mass index, recurrent episodes of acute chest, steady state
      haemoglobin, or gender with mortality. Adjusting for baseline lung function in
      SCD patients, "current" asthma [hazard ratio (HR) 11.2; 95 % confidence interval
      (CI) 2.5-50.6; p = 0.002] and smoking [HR 2.7; (95 % CI 1.3-5.5); p = 0.006] were
      significantly associated with mortality during the 10-year period. CONCLUSIONS:
      Our results indicate that young adults with SCD should be discouraged from
      smoking and their asthma aggressively treated.

PMID- 23149805
TI  - Discovery of novel SERMs with a ferrocenyl entity based on the
      oxabicyclo[2.2.1]heptene scaffold and evaluation of their antiproliferative
      effects in breast cancer cells.
AB  - We have synthesized a series of novel SERMs bearing a ferrocenyl unit based on a
      three-dimensional oxabicyclo[2.2.1]heptene core scaffold. These compounds
      displayed high receptor binding affinities as well as ERalpha or ERbeta
      selectivity. In cell proliferation assays, we found that these ligands were
      cytotoxic at micromolar concentrations in both ER-positive and ER-negative breast
      cancer cells. On further examination, we found that the antiproliferative effects
      of compounds 9b, 10h and 11b on MCF-7 cells line does not arise from
      antiestrogenicity, but rather proceeds through a cytotoxic pathway. Possible
      mechanisms for the unique activities of these ligands were also investigated by
      molecular modeling. These new ligands could act as scaffolds for the development
      of novel anti-breast cancer agents.

PMID- 23149804
TI  - Diffuse alveolar hemorrhage in coumarin users: a fibrosing interstitial pneumonia
      trigger?
AB  - BACKGROUND: Fibrosing interstitial pneumonias (IPs) include idiopathic pulmonary
      fibrosis (IPF) and nonspecific interstitial pneumonia (NSIP). It has been
      suggested that oxidative damage plays a role in the pathophysiology of idiopathic
      interstitial pneumonias. Diffuse alveolar hemorrhage (DAH) can cause oxidative
      stress. Accordingly, we hypothesized that episodes of DAH might trigger fibrosing
      IP development. METHODS: Patients using coumarins with confirmed DAH were
      retrospectively gathered during a 9 year period and reviewed for the development
      of IPF or fibrosing NSIP. RESULTS: A total of 65 patients with DAH could finally
      be included, 31 (48 %) of whom subsequently developed a fibrosing IP. The
      majority of these 31 patients developed the fibrosing IP within 3 years after DAH
      confirmation. A total of 41 (63 %) patients died within 3.0 +/- 0.9 (range 1.3
      4.7) years after the DAH diagnosis had been confirmed. Twenty-two of the deceased
      (54 %) had finally developed fibrosing IP. CONCLUSIONS: Almost half of the
      patients with established episodes of DAH developed fibrosing IP; therefore it
      seems that DAH might be a trigger for the development of fibrosing IP. This
      observation warrants prospective studies to further evaluate the clinical impact
      of these findings.

PMID- 23149806
TI  - Hydrazinonicotinamide prolongs quantum dot circulation and reduces
      reticuloendothelial system clearance by suppressing opsonization and phagocyte
      engulfment.
AB  - In this study, we investigated the effects of hydrazinonicotinamide (HYNIC)-a
      bifunctional crosslinker widely used to (99m)Tc radiolabel protein and
      nanoparticles for imaging studies-on quantum dot opsonization, macrophage
      engulfment and in vivo kinetics. In streptavidin-coated quantum dots (SA-QDots),
      conjugation with HYNIC increased the net negative charge without affecting the
      zeta potential. Confocal microscopy and fluorescence-activated cell sorting
      showed HYNIC attachment to suppress SA-QDot engulfment by macrophages.
      Furthermore, HYNIC conjugation suppressed surface opsonization by serum protein
      including IgG. When intravenously injected into mice, HYNIC conjugation
      significantly prolonged the circulation of SA-QDots and reduced their
      hepatosplenic uptake. Diminished reticuloendothelial system clearance of SA-QDots
      and aminoPEG-QDots by HYNIC conjugation was also demonstrated by in vivo and ex
      vivo optical imaging. The effects of HYNIC on the opsonization, phagocytosis and
      in vivo kinetics of quantum dots were reversed by removal of the hydrazine
      component from HYNIC. Thus, surface functionalization with HYNIC can improve the
      in vivo kinetics of quantum dots by reducing phagocytosis via suppression of
      surface opsonization.

PMID- 23149807
TI  - Effect of prolonged refrigeration on the lipid profile, lipase activity, and
      oxidative status of human milk.
AB  - OBJECTIVE: The study was aimed at evaluating the effect of prolonged
      refrigeration of fresh human milk (HM) on its fatty acid profile, free fatty acid
      content, lipase activities, and oxidative status. METHODS: HM from mothers of
      preterm newborns was collected, pooled, and placed in the neonatal intensive care
      unit (NICU) refrigerator. Pooled milk was aliquoted and analyzed within 3 hours
      of collection, and after 24, 48, 72, and 96 hours of storage. The milk samples
      were analyzed for pH, total and free fatty acid profile, lipase activity at room
      temperature and at 4 degrees C, lipase activity at room temperature in presence
      of sodium cholate (bile salt-dependent lipase), total antioxidant capacity,
      thiobarbituric acid reactive species, malondialdehyde, and conjugated diene
      concentration. The experiment was replicated in 3 independent trials. RESULTS:
      Prolonged refrigeration did not affect the fatty acid composition of breast milk,
      and preserved both its overall oxidative status and the activity of HM lipolytic
      enzymes. In particular, bile salt-dependent lipase activity, long-chain
      polyunsaturated fatty acids, and medium-chain saturated fatty acid concentrations
      were unaffected for up to 96 hours of refrigerated storage. CONCLUSIONS:
      Prolonged refrigeration of fresh HM for 96 hours maintained its overall lipid
      composition. The limited lipolysis during storage should be ascribed to the
      activity of lipoprotein lipase, responsible for the decrease in pH. Our study
      demonstrates that infants who receive expressed milk stored for up to 96 hours
      receive essentially the same supply of fatty acids and active lipases as do
      infants fed directly at the breast.

PMID- 23149808
TI  - The celiac iceberg: characterization of the disease in primary schoolchildren.
AB  - OBJECTIVE: Celiac disease (CD) has a prevalence of 0.55% to 1% in Italy.
      Identifying CD in schoolchildren to characterize CD iceberg and evaluate the
      effect of diagnosis in screening-detected children. METHODS: A total of 7377 5-
      to 8-year-old children were invited to participate. A total of 5733 salivary
      samples were collected and tested for anti-transglutaminase antibodies (tTGAb),
      using a fluid-phase radioimmunoassay. Salivary tTGAb-positive children were
      analyzed for serum antibodies (anti-endomysium antibodies, radioimmunoassay, and
      enzyme-linked immunosorbent assay tTGAb). Positive children underwent endoscopy
      and then started gluten-free diet (GFD) and periodical follow-up. RESULTS: Forty
      six subjects were found salivary tTGAb-positive and 16 border-line. Forty-five of
      46 and 5 of 15 of them were also serum antibody-positive. Forty-two children
      showed duodenal villous atrophy and 1 had only type 1 lesions. Three children
      started GFD without performing endoscopy. CD prevalence (including 23 previously
      diagnosed children with CD) was 1.2%. Considering all 65 celiacs in our sample, a
      silent CD was found in 64%, typical in 28%, atypical in 7%, and potential in 1%.
      All patients showed strict adherence to GFD, weight and stature increase, and
      well-being improvement. Eighty-five percent and all but 2 screening-detected
      children with CD had Italian parents. CONCLUSIONS: Our sample size,
      representative of primary schoolchildren of our region, demonstrated that CD
      prevalence is growing in Italy, with a modified clinical spectrum and iceberg
      deepness.

PMID- 23149810
TI  - Air contaminant statistical distributions with application to PM10 in Santiago,
      Chile.
AB  - The use of statistical distributions to predict air quality is valuable for
      determining the impact of air chemical contaminants on human health.
      Concentrations of air pollutants are treated as random variables that can be
      modeled by a statistical distribution that is positively skewed and starts from
      zero. The type of distribution selected for analyzing air pollution data and its
      associated parameters depend on factors such as emission source and local
      meteorology and topography. International environmental guideline use appropriate
      distributions to compute exceedance probabilities and percentiles for setting
      administrative targets and issuing environmental alerts. The distribution bears a
      relationship to the normal distribution, and there are theoretical - and physical
      based mechanistic arguments that support its use when analyzing air-pollutant
      data. Others distribution have also been used to model air population data, such
      as the beta, exponential, gamma, Johnson, log-logistic, Pearson, and Weibull
      distribution. One model also developed from physical-mechanistic considerations
      that has received considerable interest in recent year is the Birnbaum-Saunders
      distribution. This distribution has theoretical arguments and properties similar
      to those of the log-normal distribution, which renders it useful for modeling air
      contamination data. In this review, we have addressed the range of common
      atmospheric contaminants and the health effects they cause. We have also reviewed
      the statistical distributions that have been use to model air quality, after
      which we have detailed the problem of air contamination in Santiago, Chile. We
      have illustrated a methodology that is based on the Birnbaum-Saunders
      distributions to analyze air contamination data from Santiago, Chile. Finally, in
      the conclusions, we have provided a list of synoptic statements designed to help
      readers understand the significance of air pollution in Chile, and in Santiago,
      in particular, but that can be useful to other cites and countries.

PMID- 23149809
TI  - Ferulic acid modulates fluoride-induced oxidative hepatotoxicity in male Wistar
      rats.
AB  - The present study is aimed to evaluate the protective effect of ferulic acid (FA)
      on fluoride-induced oxidative hepatotoxicity in male Wistar rats. Fluoride (25
      mg/L) was given orally to induce hepatotoxicity for 12 weeks. Hepatic damage were
      assessed using status of pathophysiological markers like serum marker enzymes
      like aspartate transaminase, alanine transaminase, alkaline phosphatase, acid
      phosphatase, gamma glutamyl transferase, lactate dehydrogenase, bilirubin, lipid
      profile, total protein content levels, and histopathological studies. Treatment
      with FA significantly reduced the degree of histological aberrations and rescued
      lipid peroxidation, as observed from reduced levels of lipid hydroperoxides,
      nitric oxide, restored levels of enzymic and non-enzymic antioxidants, and total
      protein content, with a concomitant decline in the levels of marker enzymes and
      lipid profile in fluoride-induced rats. These results suggest that ferulic acid
      has the ability to protect fluoride-induced hepatic damage.

PMID- 23149811
TI  - Advances in the application of plant growth-promoting rhizobacteria in
      phytoremediation of heavy metals.
AB  - In this review, we briefly describe the biological application of PGPR for
      purposes of phytoremediating heavy metals. We address the agronomic practices
      that can be used to maximize the remediation potential of plants. Plant roots
      have limited ability ability mental from soil, mainly because metals have low
      solubility in the soil solution. The phytoavailability of metal is closely tired
      to the soil properties and the metabolites that are released by PGPR (e.g.,
      siderophores, organ acids, and plant growth regulators). The role played by PGPR
      may be accomplished by their direct effect on plant growth dynamics, or
      indirectly by acidification, chelation, precipitation, or immobilization of heavy
      metals in the rhizosphere. From performing this review we have formed the
      following conclusions: The most critical factor is determining how efficient
      phytoremediation of metal-contaminated soil will be is the rate of uptake of the
      metal by plants. In turn, this depends on the rate of bioavailability. We know
      from our review that beneficial bacteria exist tha can alter metal
      bioavailability of plants. Using these beneficial bacteria improves the
      performance of phytoremediation of the metal-contaminated sites. Contaminated
      sites are often nutrient poor. Such soil can be nutrient enriched by applying
      metal-tolerant microbes that provide key needed plant nutrients. Applying metal
      tolerant microbes therefore may be vital in enhancing the detoxification of heavy
      metal-contaminated soils (Glick 2003). Plant stress generated by metal
      contaminated soils can be countered by enhancing plant defense responses.
      Responses can be enhanced by alleviating the stress-mediated impact on plants by
      enzymatic hydrolysis of ACC, which is intermediate in the biosynthetic pathway of
      ethylene. These plant-microbe partnerships can act as decontaminators by
      improving phytoremediation. Soil microorganisms play a central role in
      maintaining soil structure, fertility and in remediating contaminated soils.
      Although not yet widely applied, utilizing a plant-microbe partnership is now
      being recognized as an important tool to enhance successful phytoremediaton of
      metal-contaminated sites. Hence, soil microbes are essential to soil health and
      sustainability. The key to their usefulness is their close association with, and
      positive influence on, plant growth and function. To capitalize on the early
      success of this technique and to improve it, additional research is needed on
      successful colonization and survival of inoculums under field conditions, because
      there are vital for the success of this approach. In addition, the effects of the
      interaction of PGPR and plant root-mediated process on the metal mobilization in
      soil are required, to better elucidate the mechanism that underlines bacterial
      assisted phytoremediation is important. Finally, applying PGPR-associated
      phytoremediation under field conditions is important, because, to date, only
      locally contaminated sites have been treated with this technique, by using
      microbes cultured in the laboratory.

PMID- 23149812
TI  - Toxicity reference values and tissue residue criteria for protecting avian
      wildlife exposed to methylmercury in China.
AB  - MeHg is the most biologically available and toxic from of mercury, and has the
      potential to bioaccumulate and biomagnify as it moves up the food chain. These
      characteristics result in MeHg exposure to avian wildlife at high trophic levels
      that can produce adverse effects. The toxicity of MeHg to birds was reviewed, and
      using available data, TRVs and TRCs were derived for protecting birds in China.
      The TRV and TRC values were based on concentrations of MeHg in diet (or fish
      tissue based) and tissues of birds. Two methods were applied to derive TRVs from
      concentrations in the diet or in tissues. These were the CSA and SSD approaches.
      Results of published studies show that reproductive productivity of while ibis
      was the most sensitive endpoint for MeHg exposure, and study results on white
      ibises were used for deriving the TRV and TRC values, which included applying a
      UF of 2.0. For the SSD approach, data for ten species were used to construct the
      SSD for MeHg, and to calculate the dietary-based TRV and TRC values. Using the
      CSA approach, the TRV was based on MeHg in the diet and was derived as 5.0 ng
      MeHg/g (bm).day; for feathers and blood, the TRV's were 3.16 MUg THg/g (wwt), and
      0.365 MUg THg/g (wwt), respectively. The corresponding TRCs were 15.47 ng MeHg/g
      (wwt), 3.16 MUg THg/g (wwt)respectively. The dietary-based TRV and TRC derived by
      SSD were 3.09 ng MeHg (bm)/day and 9.56 ng MeHg/g (wwt) respectively. However,
      birds tissue residue-based criteria were not available because insufficient MeHg
      effects data existed to construct an SSD for birds. We compared the criteria
      derived in our study to those developed by others, and concluded that our results
      provided more reasonable protection to Chinese avian wildlife. By comparing the
      criteria derived values we calculated to actual MeHg levels in fish and bird
      tissues, we concluded that these criteria values are useful indicators for
      screening-level risk assessments of avian wildlife in Chinese aquatic systems.
      The results of this meta-analysis might therefore have important implications for
      assessing the risk of Hg exposure to birds and for environmental management in
      China and in other regions. Moreover, because humans and top avian wildlife
      consumers are at the same trophic level, these criteria may also be used as a
      reference for human health risk assessment. The diet of birds consists of aquatic
      species from different trophic levels. However, the structure of the food web for
      avian wildlife and the environmental factors that effect their exposure to MeHg
      vary among aquatic systems. Therefore, further research results are needed on the
      food web structure of avian wildlife in Chinese aquatic systems to provide more
      insight into what constitutes adequate protection for avian wildlife.

PMID- 23149813
TI  - The biological effects and possible modes of action of nanosilver.
AB  - Novel physicochemical and biological properties have led to a versatile spectrum
      of applications for nanosized silver particles. Silver nanoparticles are applied
      primarily for their antimicrobial effects, and may variety of commercially
      available products have emerged. To better predict and prevent possible
      environmental impacts from silver nanoparticles that are derived from increasing
      production volumes and environmental release, more data on the biological effects
      are needed on appropriate model organisms. We examined the literature that
      addressed the adverse effects of silver nanoparticles on different levels of
      biological integration, including in vitro and in vivo test systems. Results of
      in vitro studies indicate a dose-dependent programmed cell death included by
      oxidative stress as main possible pathway of toxicity. Furthermore, silver
      nanoparticles may affect cellular enzymes by interference with free thiol groups
      and mimicry of endogenous ions. Similar mechanisms may apply for antibacterial
      effects produced by nonasilver. These effects are primary from the interference
      nanosilver has with bacterial cell membranes. Few in vivo studies have been
      performed to evaluated the toxic mode of action of nanosilver or to provide
      evidence for oxidative stress as an important mechanism of nanosilver toxicity.
      Organisms that are most acutely sensitive to nanosilver toxicity are the
      freshwater filter-freeding organisms. Both in vitro and in vivo studies have
      demonstrated tha silver ions released from nanoparticle surface contribute to the
      toxicity, and, indeed, some findings indicated a unique nanoparticles effect. For
      an adequate evaluation of the environmental impact of nanosilver, greater
      emphasis should be placed on combining mechanistic investigations that are
      performed in vitro, with results obtained in in vivo test systems. Future in vivo
      test system studies should emphasize long-term exposure scenarios. Moreover, the
      dietary uptake of silver nanoparticles and the potential to bioaccumulate through
      the food web should be examined in detail.

PMID- 23149814
TI  - Diazinon-chemistry and environmental fate: a California perspective.
AB  - Diazinon, first introduced in USA in 1956, is a broad-spectrum contact
      organophosphate pesticide that has been used as an insecticide, and nematicide.
      It has been ond of the most widely used insecticides in the USA for household and
      agricultural pest control. In 2004, residential use of diazinon was discontinued;
      as a result, the total amount applied has drastically decreased. [corrected].
      Consequently, the amounts of diazinon applied have been drastically decreased.
      For example, in California, the amount of diazinon applied decreased from 501,784
      kg in 2000 to 64,122 kg in 2010. Diazinon has a K(oc) value of 40-432 and is
      considered to be moderately mobile in soils. Diazinon residues have been detected
      in groundwater, drinking water wells, monitoring wells, and agricultural well.
      The highest detection frequencies and highest percentages of exceedance of the
      water quality criterion value of 0.1 MUg/L have been reported from the top five
      agricultural counties n California that had the highest diazinon use. Diazinon is
      transported in air via atmospheric processes such as direct air movement and wet
      deposition in snow and rain, although concentrations decrease with distance and
      evaluation from the source. In the environment, diazinon undergoes degradation by
      several processes, the most important of which is microbial degradation in soils.
      The rate of diazinon degradation is affected by pH, soil type, organic
      amendments, soil moisture, and the concentration of diazinon in the soil, with
      soil pH being a major influencing factor in diazinon degradation rate. Studies
      indicate tha soil organic matter is the most important factor that influences
      diazinon sorption by soils, although clay content and soil ph also play an
      important role in diazinon sorption. Diazinon is very highly to moderately toxic
      aquatic arganisms, Diazinon inhibits the enzyme acetylcholinesterase, which
      hydrolyzes the neurotransmitter acetylcholine and leads to a suite of
      intermediate syndromes including anorexia, diarrhea, generalized weakness, muscle
      tremors, abnormal posturing and behavior, depression, and health. Differences in
      metabolism among species and exposure concentrations play a vital role in
      diazinon's bioaccumulation among different aquatic organisms in a wide range of
      accumulating rates and efficiencies.

PMID- 23149815
TI  - Stromal cell-derived factor-1alpha as a novel biomarker for hyperlipidemia.
AB  - Stromal cell-derived factor-1 (SDF-1) is expressed in a wide variety of organs,
      such as heart, and plays a pivotal role in the mobilization of hematopoietic stem
      and progenitor cells in bone marrow. SDF-1alpha, a common subtype of SDF-1, may
      control hematopoiesis and angiogenesis, but its role in the pathogenesis of
      hyperlipidemia is unknown. The aim of this study was to determine the role of SDF
      1alpha in the pathogenesis of hyperlipidemia. First, log-transformed SDF-1alpha
      serum levels (logSDF-1alpha) were significantly higher in male patients with
      borderline high lipid profile (BHLP; n=28; 2.15+/-0.08 ng/ml) compared to control
      subjects (n=37; 1.94+/-0.06 ng/ml; P<0.01). The logSDF-1alpha in male patients
      with high lipid profile (HLP; n=33; 1.95+/-0.08 ng/ml) were lower than BHLP
      patients (P<0.01). The logSDF-1alpha was positively associated with HDL-C only in
      female patients (n=125; r=0.379, P=0.016). These results suggest the different
      pathophysiology in male and female patients with hyperlipidemia. Moreover, flow
      cytometry analysis showed that expression of the SDF-1alpha receptor, CXC
      chemokine receptor 4, was lower in peripheral blood mononuclear cells of patients
      with BHLP (n=10) and HLP (n=10), compared to control subjects (n=10; P<0.001).
      Lastly, peripheral blood leukocyte, neutrophil and lymphocyte counts were higher
      in BHLP patients (n=62; P<0.05). Taken together, we suggest SDF-1alpha as a
      biomarker of hyperlipidemia that may be helpful to uncover the pathogenesis of
      hyperlipidemia.

PMID- 23149816
TI  - Clinical impact of genetically determined platelet reactivity.
AB  - Dual antiplatelet therapy with aspirin and clopidogrel dramatically reduced the
      rate of major adverse cardiac events following percutaneous coronary
      intervention. Clopidogrel is a prodrug which requires a two-step hepatic
      biotransformation thanks to the cytochrome P450 (CYP450) enzyme system. Genetic
      polymorphism of CYP450 system (e.g., CYP2C19*2) responsible for altered
      clopidogrel metabolism is a major cause of high on-treatment platelet reactivity
      (HTPR), which translates into thrombotic events in stented patients. Studies
      demonstrated that HTPR could be overcome in poor metabolizers thanks to increased
      loading doses or maintenance doses of clopidogrel or with the use of more potent
      antiplatelet agents such as prasugrel. Other genetic polymorphisms have also been
      correlated with HTPR: ABCB1, ATP2B2, and TIAM2. Large-scale randomized trials
      with clinical endpoints remain necessary to determine the optimal antiplatelet
      therapy in patients carrying genetic polymorphism associated with HTPR and
      thrombotic events.

PMID- 23149817
TI  - Evaluation of arene ruthenium(II) N-heterocyclic carbene complexes as
      organometallics interacting with thiol and selenol containing biomolecules.
AB  - Metal complexes with N-heterocyclic carbene (NHC) ligands have been widely used
      in catalytic chemistry and are now increasingly considered for the development of
      new chemical tools and metal based drugs. Ruthenium complexes of the type (p
      cymene)(NHC)RuCl(2) interacted with biologically relevant thiols and selenols,
      which resulted in the inhibition of enzymes such as thioredoxin reductase or
      cathepsin B. Pronounced antiproliferative effects could be obtained provided that
      an appropriate cellular uptake was achieved. Inhibition of tumor cell growth was
      accompanied by a perturbation of metabolic parameters such as cellular
      respiration.

PMID- 23149818
TI  - Interleukin 15 provides relief to CTLs from regulatory T cell-mediated
      inhibition: implications for adoptive T cell-based therapies for lymphoma.
AB  - PURPOSE: Systemic administration of recombinant interleukin (IL)-2 is used to
      support the expansion and persistence of adoptively transferred antigen-specific
      CTLs in patients with cancer. However, IL-2 also expands regulatory T cells
      (Treg) that in turn impair the antitumor activity of CTLs. As recombinant IL-15
      is approaching clinical applications, we assessed the effects of this cytokine on
      the proliferation and antitumor activity of CTLs in the presence of Tregs. We
      used the model of adoptive transfer of Epstein-Barr virus (EBV)-CTLs, as these
      cells induce responses in patients with EBV-associated Hodgkin lymphoma, and
      Tregs are frequently abundant in these patients. EXPERIMENTAL DESIGN: Tregs were
      isolated from the peripheral blood of healthy donors and patients with Hodgkin
      lymphoma or from Hodgkin lymphoma tumors and assessed for their ability to
      inhibit the proliferation and antitumor activity of EBV-CTLs in the presence of
      IL-15 or IL-2. Specific molecular pathways activated by IL-15 were also explored.
      RESULTS: We found that in the presence of Tregs, IL-15, but not IL-2, promoted
      the proliferation, effector function, and resistance to apoptosis of effectors T
      cells and EBV-CTLs. IL-15 did not reverse or block Tregs but instead
      preferentially supported the proliferation of CTLs and effector T cells as
      compared with Tregs. CONCLUSIONS: IL-15 selectively favors the survival,
      proliferation, and effector function of antigen-specific CTLs in the presence of
      Tregs, and thus IL-15, unlike IL-2, would have a significant impact in sustaining
      expansion and persistence of adoptively transferred CTLs in patients with cancer,
      including those infused with EBV-CTLs for treatment of EBV-associated
      malignancies.

PMID- 23149819
TI  - Progression-free survival as a surrogate endpoint for median overall survival in
      metastatic colorectal cancer: literature-based analysis from 50 randomized first
      line trials.
AB  - PURPOSE: To evaluate progression-free survival (PFS) as a potential surrogate
      endpoint (SEP) for overall survival (OS) in metastatic colorectal cancer (mCRC)
      with a focus on applicability to trials containing targeted therapy with anti
      VEGF- or anti-EGF receptor (EGFR)-directed monoclonal antibodies. EXPERIMENTAL
      DESIGN: A systematic literature search of randomized trials of first-line
      chemotherapy for mCRC reported from January 2000 to January 2012 was conducted.
      Adjusted weighted linear regression was used to calculate correlations within PFS
      and OS (endpoints; R(EP)) and between treatment effects on PFS and on OS
      (treatment effects; R(TE)). RESULTS: Fifty trials reflecting 22,736 patients met
      the inclusion criteria. Correlation between treatment effects on PFS and OS and
      between the endpoints PFS and OS was high across all studies (R(TE) = 0.87, R(EP)
      = 0.86). This was also observed in chemotherapy-only trials (R(TE) = 0.93, R(EP)
      = 0.81) but less so for trials containing monoclonal antibodies (R(TE) = 0.47;
      R(EP) = 0.52). Limiting the analysis to bevacizumab-based studies (11 trials,
      3,310 patients) again yielded high correlations between treatment effects on PFS
      and on OS (R(TE) = 0.84), whereas correlation within PFS and OS was low (R(EP) =
      0.45). In 7 trials (1,335 patients) investigating cetuximab- or panitumumab-based
      studies, contrasting correlations with very wide confidence intervals were
      observed (R(TE) = 0.28; R(EP) = 0.96). CONCLUSIONS: PFS showed consistently high
      correlation with OS of an order that would justify its use as an SEP in
      chemotherapy regimens. For validation of surrogacy in anti-VEGF and anti-EGFR
      directed therapies, further research and a larger set of trials is needed.

PMID- 23149820
TI  - Targeting CXCR1/2 significantly reduces breast cancer stem cell activity and
      increases the efficacy of inhibiting HER2 via HER2-dependent and -independent
      mechanisms.
AB  - PURPOSE: Breast cancer stem-like cells (CSC) are an important therapeutic target
      as they are predicted to be responsible for tumor initiation, maintenance, and
      metastases. Interleukin (IL)-8 is upregulated in breast cancer and is associated
      with poor prognosis. Breast cancer cell line studies indicate that IL-8 via its
      cognate receptors, CXCR1 and CXCR2, is important in regulating breast CSC
      activity. We investigated the role of IL-8 in the regulation of CSC activity
      using patient-derived breast cancers and determined the potential benefit of
      combining CXCR1/2 inhibition with HER2-targeted therapy. EXPERIMENTAL DESIGN: CSC
      activity of metastatic and invasive human breast cancers (n = 19) was assessed ex
      vivo using the mammosphere colony-forming assay. RESULTS: Metastatic fluid IL-8
      level correlated directly with mammosphere formation (r = 0.652; P < 0.05; n =
      10). Recombinant IL-8 directly increased mammosphere formation/self-renewal in
      metastatic and invasive breast cancers (n = 17). IL-8 induced activation of
      EGFR/HER2 and downstream signaling pathways and effects were abrogated by
      inhibition of SRC, EGFR/HER2, phosphoinositide 3-kinase (PI3K), or MEK.
      Furthermore, lapatinib, which targets EGFR/HER2, inhibited the mammosphere
      promoting effect of IL-8 in both HER2-positive and negative patient-derived
      cancers. CXCR1/2 inhibition also blocked the effect of IL-8 on mammosphere
      formation and added to the efficacy of lapatinib in HER2-positive cancers.
      CONCLUSIONS: These studies establish a role for IL-8 in the regulation of patient
      derived breast CSC activity and show that IL-8/CXCR1/2 signaling is partly
      mediated via a novel SRC and EGFR/HER2-dependent pathway. Combining CXCR1/2
      inhibitors with current HER2-targeted therapies has potential as an effective
      therapeutic strategy to reduce CSC activity in breast cancer and improve the
      survival of HER2-positive patients.

PMID- 23149822
TI  - EJNMMI: the European way of communicating science.

PMID- 23149821
TI  - Should HIV-infected patients be screened for silent myocardial ischaemia using
      gated myocardial perfusion SPECT?
AB  - PURPOSE: A higher prevalence of cardiovascular risk factors (CRFs) in HIV
      infected patients, together with chronic infection and treatments, has resulted
      in an increased risk of silent myocardial ischaemia (SMI). The objective of this
      study was to evaluate whether myocardial SPECT should be used for screening HIV
      infected patients with no clinical symptoms of coronary artery disease. METHODS:
      The prevalence of SMI detected by myocardial SPECT was determined in 94 HIV
      infected patients with a normal clinical cardiovascular examination in relation
      to anthropomorphic parameters, CRFs, inflammatory and HIV infection status, and
      treatment. RESULTS: Coronary artery disease was detected in nine patients (eight
      with ischaemia, one with myocardial infarction), corresponding to 9.6 %
      positivity. All but two of the scintigraphic diagnoses of ischaemia were
      confirmed by coronarography. Univariate analysis revealed that the overall number
      of CRFs and the combination of gender and age were associated with a diagnosis of
      SMI (p < 0.05). According to multivariate analysis, the only independent
      parameter significantly associated with the scintigraphic diagnosis of SMI was
      the combination of gender and age (p = 0.01). All the positive myocardial SPECT
      scans were in men older than 52 years with at least two other CRFs. In this
      subpopulation of 47 patients, the prevalence of SMI detected by myocardial SPECT
      reached 19.2 %. CONCLUSION: In male HIV-infected patients older than 52 years and
      with at least two other CRFs, screening for SMI using myocardial SPECT was about
      four times more likely to be positive than in the general population. This may
      motivate physicians to advise these patients to undergo more systematic screening
      for SMI using this technique.

PMID- 23149823
TI  - Negative regulatory responses to metabolically triggered inflammation impair
      renal epithelial immunity in diabetes mellitus.
AB  - Diabetes mellitus is characterized by chronic inflammation and increased risk of
      infections, particularly of tissues exposed to the external environment. However,
      the causal molecular mechanisms that affect immune cells and their functions in
      diabetes are unclear. Here we show, by transcript and protein analyses,
      signatures of glucose-induced tissue damage, chronic inflammation, oxidative
      stress, and dysregulated expression of multiple inflammation- and immunity
      related molecules in diabetic kidneys compared with non-diabetic controls.
      Abnormal signaling involving cytokines, G-protein coupled receptors, protein
      kinase C isoforms, mitogen-activated protein kinases, nuclear factor-kappaB
      (NFkappaB), and Toll-like receptors (TLR) were evident. These were accompanied by
      overexpression of negative regulators of NFkappaB, TLR, and other proinflammatory
      pathways, e.g., A20, SOCS1, IRAK-M, IkappaBalpha, Triad3A, Tollip, SIGIRR, and
      ST2L. Anti-inflammatory and immunomodulatory molecules, e.g., IL-10, IL-4, and
      TSLP that favor TH2 responses were strongly induced. These molecular indicators
      of immune dysfunction led us to detect the cryptic presence of bacteria and human
      cytomegalovirus in more than one third of kidneys of diabetic subjects but none
      in non-diabetic kidneys. Similar signaling abnormalities could be induced in
      primary human renal tubular epithelial (but not mesangial) cell cultures exposed
      to high glucose, proinflammatory cytokines and methylglyoxal, and were reversed
      by combined pharmacological treatment with an antioxidant and a PKC inhibitor.
      Our results suggest that diabetes impairs epithelial immunity as a consequence of
      chronic and inappropriate activation of counter-regulatory immune responses,
      which are otherwise physiological protective mechanisms against inflammation. The
      immune abnormalities and cryptic renal infections described here may contribute
      to progression of diabetic nephropathy.

PMID- 23149824
TI  - The chloride channel/transporter Slc26a9 regulates the systemic arterial pressure
      and renal chloride excretion.
AB  - Apical chloride secretory pathways in the kidney medullary collecting duct are
      thought to play an important role in the modulation of final urine composition
      and regulation of systemic vascular volume and/or blood pressure. However, the
      molecular identity of these molecules has largely remained unknown. Here, we
      demonstrate that Slc26a9, an electrogenic chloride channel/transporter, is
      localized on the apical membrane of principal cells in the kidney medullary
      collecting duct and mediates chloride secretion. Mice with the genetic deletion
      of Slc26a9 show significant reduction in renal chloride excretion when fed a diet
      high in salt or subjected to water deprivation. Arterial pressure measurements
      indicated that Slc26a9 knockout (Slc26a9(-/-)) mice are hypertensive under
      baseline conditions and increase their blood pressure further within 48 h of
      switching to a high-salt diet. These results suggest that Slc26a9 plays an
      important role in renal chloride/fluid excretion and arterial pressure
      regulation. We propose that impaired SLC26A9 activity in humans may interfere
      with the excretion of excess salt and result in hypertension.

PMID- 23149825
TI  - Direct rAAV SOX9 administration for durable articular cartilage repair with
      delayed terminal differentiation and hypertrophy in vivo.
AB  - Direct gene transfer strategies are of promising value to treat articular
      cartilage defects. Here, we tested the ability of a recombinant adeno-associated
      virus (rAAV) SOX9 vector to enhance the repair of cartilage lesions in vivo. The
      candidate construct was provided to osteochondral defects in rabbit knee joints
      vis-a-vis control (lacZ) vector treatment and to cells relevant of the repair
      tissue (mesenchymal stem cells, chondrocytes). Efficient, long-term transgene
      expression was noted within the lesions (up to 16 weeks) and in cells in vitro
      (21 days). Administration of the SOX9 vector was capable of stimulating the
      biological activities in vitro and over time in vivo. SOX9 treatment in vivo was
      well tolerated, leading to improved cartilage repair processes with enhanced
      production of major matrix components. Remarkably, application of rAAV SOX9
      delayed premature terminal differentiation and hypertrophy in the newly formed
      cartilage, possible due to contrasting effects of SOX9 on RUNX2 and beta-catenin
      osteogenic expression in this area. Most strikingly, SOX9 treatment improved the
      reconstitution of the subchondral bone in the defects, possibly due to an
      increase in RUNX2 expression in this location. These findings show the potential
      of direct rAAV gene delivery as an efficient tool to treat cartilage lesions.

PMID- 23149827
TI  - Coronary artery disease. Are beta-blockers truly helpful in patients with CAD?
AB  - In a large, new, observational study, beta-blocker treatment did not improve
      clinical outcomes in patients with coronary artery disease (CAD), including those
      with previous myocardial infarction, and was associated with more events in
      individuals with risk factors only. The role of beta-blockers for secondary
      prevention in these patients should be reconsidered.

PMID- 23149828
TI  - Intervention: Logistic Clinical SYNTAX score.

PMID- 23149826
TI  - Possible involvement of PPARgamma-associated eNOS signaling activation in
      rosuvastatin-mediated prevention of nicotine-induced experimental vascular
      endothelial abnormalities.
AB  - Nicotine exposure via cigarette smoking and tobacco chewing is associated with
      vascular complications. The present study investigated the effect of rosuvastatin
      in nicotine (2 mg/kg/day, i.p., 4 weeks)-induced vascular endothelial dysfunction
      (VED) in rats. The development of VED was assessed by employing isolated aortic
      ring preparation and estimating aortic and serum nitrite/nitrate concentration.
      Further, scanning electron microscopy and hematoxylin-eosin staining of thoracic
      aorta were performed to assess the vascular endothelial integrity. Moreover,
      oxidative stress was assessed by estimating aortic superoxide anion generation
      and serum thiobarbituric acid-reactive substances. The nicotine administration
      produced VED by markedly reducing acetylcholine-induced endothelium-dependent
      relaxation, impairing the integrity of vascular endothelium, decreasing aortic
      and serum nitrite/nitrate concentration, increasing oxidative stress, and
      inducing lipid alteration. However, treatment with rosuvastatin (10 mg/kg/day,
      i.p., 4 weeks) markedly attenuated nicotine-induced vascular endothelial
      abnormalities, oxidative stress, and lipid alteration. Interestingly, the co
      administration of peroxisome proliferator-activated receptor gamma (PPARgamma)
      antagonist, GW9662 (1 mg/kg/day, i.p., 2 weeks) submaximally, significantly
      prevented rosuvastatin-induced improvement in vascular endothelial integrity,
      endothelium-dependent relaxation, and nitrite/nitrate concentration in rats
      administered nicotine. However, GW9662 co-administration did not affect
      rosuvastatin-associated vascular anti-oxidant and lipid-lowering effects. The
      incubation of aortic ring, isolated from rosuvastatin-treated nicotine
      administered rats, with L-NAME (100 MUM), an inhibitor of nitric oxide synthase
      (NOS), significantly attenuated rosuvastatin-induced improvement in acetylcholine
      induced endothelium-dependent relaxation. Rosuvastatin prevents nicotine-induced
      vascular endothelial abnormalities by activating PPARgamma and endothelial NOS
      signaling pathways. Moreover, the PPARgamma-independent anti-oxidant and lipid
      lowering effects of rosuvastatin might additionally play a role in the
      improvement of vascular endothelial function.

PMID- 23149829
TI  - Heart failure: Exercise training--a magic bullet for chronic heart failure?

PMID- 23149830
TI  - Screening for rheumatic heart disease: current approaches and controversies.
AB  - Rheumatic heart disease (RHD) is a leading cause of cardiac disease among
      children in developing nations, and in indigenous populations of some
      industrialized countries. In endemic areas, RHD has long been a target of
      screening programmes that, historically, have relied on cardiac auscultation. The
      evolution of portable echocardiographic equipment has changed the face of
      screening for RHD over the past 5 years, with greatly improved sensitivity.
      However, concerns have been raised about the specificity of echocardiography, and
      the interpretation of minor abnormalities poses new challenges. The natural
      history of RHD in children with subclinical abnormalities detected by
      echocardiographic screening remains unknown, and long-term follow-up studies are
      needed to evaluate the significance of detecting these changes at an early stage.
      For a disease to be deemed suitable for screening from a public health
      perspective, it needs to fulfil a number of criteria. RHD meets some, but not
      all, of these criteria. If screening programmes are to identify additional cases
      of RHD, parallel improvements in the systems that deliver secondary prophylaxis
      are essential.

PMID- 23149832
TI  - Dyslipidemia: Phase III trial of mipomersen in heterozygous FH.

PMID- 23149833
TI  - Device therapy: Reuse of ICDs in developing countries--'proof of concept' data
      published.

PMID- 23149831
TI  - Surgical ventricular restoration for the treatment of heart failure.
AB  - Heart failure (HF) is an emerging epidemic affecting 15 million people in the USA
      and Europe. HF-related mortality was unchanged between 1995 and 2009, despite a
      decrease in the incidence of cardiovascular disease. Conventional explanations
      include an aging population and improved treatment of acute myocardial infarction
      and HF. An adverse relationship between structure and function is the central
      theme in patients with systolic dysfunction. The normal elliptical ventricular
      shape becomes spherical in ischemic, valvular, and nonischemic dilated
      cardiomyopathy. Therapeutic decisions should be made on the basis of ventricular
      volume rather than ejection fraction. When left ventricular end-systolic volume
      index exceeds 60 ml/m2, medical therapy, CABG surgery, and mitral repair have
      limited benefit. This form-function relationship can be corrected by surgical
      ventricular restoration (SVR), which returns the ventricle to a normal volume and
      shape. Consistent early and late benefits in the treatment of ischemic dilated
      cardiomyopathy with SVR have been reported in >5,000 patients from various
      international centers. The prospective, randomized STICH trial did not confirm
      these findings and the reasons for this discrepancy are examined in detail.
      Future surgical options for SVR in nonischemic and valvular dilated
      cardiomyopathy, and its integration with left ventricular assist devices and cell
      therapy, are described.

PMID- 23149835
TI  - Valvular disease: Aortic valve-in-valve replacement.

PMID- 23149836
TI  - Atrial fibrillation. First-line catheter ablation therapy--too much too soon?

PMID- 23149837
TI  - Risk factors: Long-term effects of air pollution.

PMID- 23149834
TI  - Adipose tissue: friend or foe?
AB  - The perception of adipose tissue has changed considerably with the dramatic
      increase in the incidence of obesity and obesity-related comorbidities over the
      past 3 decades. Excess fat is no longer associated with wealth, but is instead
      recognized as a risk factor for many diseases. Adipose tissue is increasingly
      being identified as a vital, complex endocrine organ, and not simply as a fat
      store. Not all fat is created equal--regional, developmental, structural, and
      functional variations exist. Epicardial adipose tissue is a metabolically active
      organ producing a number of factors that modulate cardiac structure and function.
      The global epidemic of obesity and metabolic syndrome imposes a major disease
      burden, particularly of cardiovascular disease. In this Review, we describe the
      various types of adipose tissue--their developmental biology, differentiation,
      cell heterogeneity, and functional characteristics. We discuss the link between
      adipose tissue and inflammation, the signaling factors released by adipose
      tissue, as well as cardiac adiposity and its relevance to cardiovascular
      diseases. Finally, we review the myocardial regenerative potential of adipose
      tissue-derived stem cells. We believe that a thorough understanding of adipose
      tissue is of great clinical value.

PMID- 23149838
TI  - Arrhythmias: Epinephrine test for sudden cardiac death--is it too early?

PMID- 23149839
TI  - Sedimentation and remobilization of radiocesium in the coastal area of Ibaraki,
      70 km south of the Fukushima Dai-ichi Nuclear Power Plant.
AB  - Sedimentation and remobilization processes of radiocesium were investigated from
      time-series observations at nine stations in the coastal area of Ibaraki, 70-110
      km south of the Fukushima Dai-ichi Nuclear Power Plant (1FNPP). Sediment samples
      were collected four times between June 2011 and January 2012, and concentrations
      of radiocesium as well as sediment properties such as grain size and elemental
      compositions were analyzed. Cumulative inventory of (137)Cs in sediment (0-10 cm)
      ranged between 4 * 10(3) and 3 * 10(4) Bq/m(2) as of January 2012. This amount
      was generally higher at stations nearer 1FNPP and has remained at the same level
      since August 2011. From these results, it can be inferred that dissolved
      radiocesium advected southward from the region adjacent to the 1FNPP and was
      deposited to the sediment of the study area in the early stage after the
      accident. The incorporation of radiocesium into sediments was almost
      irreversible, and higher concentrations of (137)Cs were obtained from the finer
      grained fraction of sediments. In the northern offshore stations, resuspension of
      the fine-grained sediments formed a high-turbidity layer 10-20 m above the
      seabed. These results indicate that radiocesium-enriched fine particles were
      transported from the coast to offshore regions through the bottom high-turbidity
      layer.

PMID- 23149840
TI  - Macrophytes, epipelic biofilm, and invertebrates as biotic indicators of physical
      habitat degradation of lowland streams (Argentina).
AB  - Our objective was to assess the effect of the physical habitat degradation in
      three lowland streams of Argentina that are subject to different land uses. To
      address this matter, we looked into some physical habitat alterations, mainly the
      water quality and channel changes, the impact on macrophytes' community, and the
      structural and functional descriptors of the epipelic biofilm and invertebrate
      assemblages. As a consequence of physical and chemical perturbations, we
      differentiated sampling sites with different degradation levels. The low degraded
      sites were affected mainly for the suburban land use, the moderately degraded
      sites for the rural land use, and the highly degraded sites for the urban land
      use. The data shows that the biotic descriptors that best reflected the
      environmental degradation were vegetation cover and macrophytes richness, the
      dominance of tolerant species (epipelic biofilm and invertebrates), algal
      biomass, O2 consumption by the epipelic biofilm, and invertebrates' richness and
      diversity. Furthermore, the results obtained highlight the importance of the
      macrophytes in the lowland streams, where there is a poor diversification of
      abiotic substrates and where the macrophytes not only provide shelter but also a
      food source for invertebrates and other trophic levels such as fish. We also
      noted that both in benthic communities, invertebrates and epipelic biofilm
      supplied different information: the habitat's physical structure provided by the
      macrophytes influenced mainly the invertebrate descriptors; meanwhile, the water
      quality mainly influenced most of the epipelic biofilm descriptors.

PMID- 23149841
TI  - Air quality assessment of Estarreja, an urban industrialized area, in a coastal
      region of Portugal.
AB  - Despite the increasing concern given to air quality in urban and industrial areas
      in recent years, particular emphasis on regulation, control, and reduction of air
      pollutant emissions is still necessary to fully characterize the chain emissions
      air quality-exposure-dose-health effects, for specific sources. The Estarreja
      region was selected as a case study because it has one of the largest chemical
      industrial complexes in Portugal that has been recently expanded, together with a
      growing urban area with an interesting location in the Portuguese coastland and
      crossed by important road traffic and rail national networks. This work presents
      the first air quality assessment for the region concerning pollutant emissions
      and meteorological and air quality monitoring data analysis, over the period 2000
      2009. This assessment also includes a detailed investigation and characterization
      of past air pollution episodes for the most problematic pollutants: ozone and
      PM10. The contribution of different emission sources and meteorological
      conditions to these episodes is investigated. The stagnant meteorological
      conditions associated with local emissions, namely industrial activity and road
      traffic, are the major contributors to the air quality degradation over the study
      region. A set of measures to improve air quality--regarding ozone and PM10 levels
      -is proposed as an air quality management strategy for the study region.

PMID- 23149843
TI  - Effects of bis-carbazole based D-pi-A sensitizers on solar energy capture in
      DSSCs.
AB  - A new series of molecular engineered dyes having a carbazole (CA) based bulky
      donor was synthesized and compared to a previously studied set of dyes having a
      diphenyl amine (DP) donor for their use in dye sensitized solar cells. In this
      work, their photophysical, electrochemical, and kinetic properties were measured
      and molecular modeling methods were used to predict their electronic and physical
      properties. Regarding the latter, TDDFT studies adopting different exchange
      correlation functionals were performed to predict solar capture behavior of these
      sensitizers. The calculated electronic energies showed that the introduction of
      the bulky CA donor gave a greater negative shift on E(HOMO) rather than E(LUMO),
      imparting the CA series of dyes a red shifted absorption. On the other hand,
      tuning of the spacer unit by using different heterocylic rings was sensitive to
      the shift of E(LUMO) shift. Better light absorption and driving force of devices
      based on the CA series were counteracted with negative effects related to the
      electron injection yield and electron recombination lifetime. The origin of the
      lower efficiency of the CA dye based devices was investigated in terms of dye
      load, charge recombination lifetime, in tandem with modeling studies. Results
      from assessing the effects of different heterocyclic rings, as a pi conjugation
      unit on photovoltaic performance showed that the thiophene unit gave the highest
      current. On the other hand, CA- and DP-based dyes having an N-methyl pyrrole unit
      afforded the highest V(oc). The best DSSC performance in the CA series was
      achieved by the thiophene derivative, where eta = 3.05% with J(sc) = 6.29 mA cm(
      2), V(oc) = 673 mV and FF = 0.72 under 100 mW m(-2) irradiation.

PMID- 23149842
TI  - An inherited NBN mutation is associated with poor prognosis prostate cancer.
AB  - BACKGROUND: To establish the contribution of eight founder alleles in three DNA
      damage repair genes (BRCA1, CHEK2 and NBS1) to prostate cancer in Poland, and to
      measure the impact of these variants on survival among patients. METHODS: Three
      thousand seven hundred fifty men with prostate cancer and 3956 cancer-free
      controls were genotyped for three founder alleles in BRCA1 (5382insC, 4153delA,
      C61G), four alleles in CHEK2 (1100delC, IVS2+1G>A, del5395, I157T), and one
      allele in NBS1 (657del5). RESULTS: The NBS1 mutation was detected in 53 of 3750
      unselected cases compared with 23 of 3956 (0.6%) controls (odds ratio (OR)=2.5;
      P=0.0003). A CHEK2 mutation was seen in 383 (10.2%) unselected cases and in 228
      (5.8%) controls (OR=1.9; P<0.0001). Mutation of BRCA1 (three mutations combined)
      was not associated with the risk of prostate cancer (OR=0.9; P=0.8). In a
      subgroup analysis, the 4153delA mutation was associated with early-onset (age <=
      60 years) prostate cancer (OR=20.3, P=0.004). The mean follow-up was 54 months.
      Mortality was significantly worse for carriers of a NBS1 mutation than for non
      carriers (HR=1.85; P=0.008). The 5-year survival for men with an NBS1 mutation
      was 49%, compared with 72% for mutation-negative cases. CONCLUSION: A mutation in
      NBS1 predisposes to aggressive prostate cancer. These data are relevant to the
      prospect of adapting personalised medicine to prostate cancer prevention and
      treatment.

PMID- 23149844
TI  - Vascular Gas6 contributes to thrombogenesis and promotes tissue factor up
      regulation after vessel injury in mice.
AB  - Gas6 (growth-arrest specific gene 6) plays a role in thrombus stabilization. Gas6
      null (-/-) mice are protected from lethal venous and arterial thromboembolism
      through platelet signaling defects induced only by 5 MUM ADP and 10 MUM of the
      thromboxane analog, U46619. This subtle platelet defect, despite a dramatic
      clinical phenotype, raises the possibility that Gas6 from a source other than
      platelets contributes to thrombus formation. Thus, we hypothesize that Gas6
      derived from the vascular wall plays a role in venous thrombus formation. Bone
      marrow transplantation and platelet depletion/reconstitution experiments
      generating mice with selective ablations of Gas6 from either the hematopoietic or
      nonhematopoietic compartments demonstrate an approximately equal contribution by
      Gas6 from both compartments to thrombus formation. Tissue factor expression was
      significantly reduced in the vascular wall of Gas6(-/-) mice compared with WT. In
      vitro, thrombin-induced tissue factor expression was reduced in Gas6(-/-)
      endothelial cells compared with wild-type endothelium. Taken together, these
      results demonstrate that vascular Gas6 contributes to thrombus formation in vivo
      and can be explained by the ability of Gas6 to promote tissue factor expression
      and activity. These findings support the notion that vascular wall-derived Gas6
      may play a pathophysiologic role in venous thromboembolism.

PMID- 23149845
TI  - Outcome and pathologic classification of children and adolescents with
      mediastinal large B-cell lymphoma treated with FAB/LMB96 mature B-NHL therapy.
AB  - Mediastinal large B-cell lymphoma (MLBL) represents 2% of mature B-cell non
      Hodgkin lymphoma in patients <= 18 years of age. We analyzed data from childhood
      and adolescent patients with stage III MLBL (n = 42) and non-MLBL DLBCL (n = 69)
      treated with Group B therapy in the French-American-British/Lymphome Malins de
      Burkitt (FAB/LMB) 96 study. MLBL patients had a male/female 26/16; median age,
      15.7 years (range, 12.5-19.7); and LDH < 2 versus >= 2 * the upper limit of
      normal, 23:19. Six MLBL patients (14%) had < a 20% response to initial COP
      (cyclophosphamide, vincristine, and prednisone) therapy. Central pathology
      revealed approximately 50% with classical features of primary MLBL. Five-year
      event-free survival for the stage III MLBL and non-MLBL DLBCL groups was 66% (95%
      confidence interval [CI], 49%-78%) and 85% (95% CI, 71%-92%), respectively (P <
      .001; 14%). The 5-year overall survival in the 42 MLBL patients was 73% (95% CI,
      56%-84%). We conclude that MLBL in adolescent patients is associated with
      significantly inferior event-free survival compared with stage III non-MLBL DLBCL
      and can be of multiple histologies. Alternate treatment strategies should be
      investigated in the future taking into account both adult MLBL approaches and
      more recent biologic findings in adult MLBL.

PMID- 23149846
TI  - How I treat thrombocytopenia in pregnancy.
AB  - A mild thrombocytopenia is relatively frequent during pregnancy and has generally
      no consequences for either the mother or the fetus. Although representing no
      threat in the majority of patients, thrombocytopenia may result from a range of
      pathologic conditions requiring closer monitoring and possible therapy. Two
      clinical scenarios are particularly relevant for their prevalence and the issues
      relating to their management. The first is the presence of isolated
      thrombocytopenia and the differential diagnosis between primary immune
      thrombocytopenia and gestational thrombocytopenia. The second is thrombocytopenia
      associated with preeclampsia and its look-alikes and their distinction from
      thrombotic thrombocytopenic purpura and the hemolytic uremic syndrome. In this
      review, we describe a systematic approach to the diagnosis and treatment of these
      disease entities using a case presentation format. Our discussion includes the
      antenatal and perinatal management of both the mother and fetus.

PMID- 23149847
TI  - CD59 deficiency is associated with chronic hemolysis and childhood relapsing
      immune-mediated polyneuropathy.
AB  - CD59 deficiency is a common finding in RBCs and WBCs in patients with chronic
      hemolysis suffering from paroxysmal nocturnal hemoglobinuria in which the
      acquired mutation in the PIGA gene leads to membrane loss of
      glycosylphosphatidylinositol-anchored membrane proteins, including CD59. The
      objective of the present study was to elucidate the molecular basis of childhood
      familial chronic Coombs-negative hemolysis and relapsing polyneuropathy
      presenting as chronic inflammatory demyelinating polyradiculoneuropathy in
      infants of North-African Jewish origin from 4 unrelated families. A founder
      mutation was searched for using homozygosity mapping followed by exome
      sequencing. The expression of CD59, CD55, and CD14 was examined in blood cells by
      flow cytometry followed by Western blot of the CD59 protein. A homozygous
      missense mutation, p.Cys89Tyr in CD59, was identified in all patients. The
      mutation segregated with the disease in the families and had a carrier rate of
      1:66 among Jewish subjects of North-African origin. The mutated protein was
      present in the patients' cells in reduced amounts and was undetectable on the
      membrane surface. Based on the results of the present study, we conclude that the
      Cys89Tyr mutation in CD59 is associated with a failure of proper localization of
      the CD59 protein in the cell surface. This mutation is manifested clinically in
      infancy by chronic hemolysis and relapsing peripheral demyelinating disease.

PMID- 23149849
TI  - Surgical resection after downsizing chemotherapy for initially unresectable
      locally advanced biliary tract cancer: a retrospective single-center study.
AB  - BACKGROUND: Surgical resection is the only method for curative treatment of
      biliary tract cancer (BTC). Recently, an improved efficacy has been revealed in
      patients with initially unresectable locally advanced BTC to improve the
      prognosis by the advent of useful cancer chemotherapy. The aim of this study was
      to evaluate the effect of downsizing chemotherapy in patients with initially
      unresectable locally advanced BTC. METHODS: Initially unresectable locally
      advanced cases were defined as those in which therapeutic resection could not be
      achieved even by proactive surgical resection. Gemcitabine was administered
      intravenously once a week for 3 weeks followed by 1 week's respite. Patients
      whose disease responded to chemotherapy were reevaluated to determine whether
      their tumor was resectable. RESULTS: Chemotherapy with gemcitabine was provided
      to 22 patients with initially unresectable locally advanced BTC. Tumor was
      significantly downsized in nine patients, and surgical resection was performed in
      8 (36.4%) of 22 patients. Surgical resection resulted in R0 resection in four
      patients and R1 resection in four patients. Patients who underwent surgical
      resection had a significantly longer survival compared with those unable to
      undergo surgery. CONCLUSIONS: Preoperative chemotherapy enables the downsizing of
      initially unresectable locally advanced BTC, with radical resection made possible
      in a certain proportion of patients. Downsizing chemotherapy should be
      proactively carried out as a multidisciplinary treatment strategy for patients
      with initially unresectable locally advanced BTC with the aim of expanding the
      surgical indication.

PMID- 23149848
TI  - Biased agonism of protease-activated receptor 1 by activated protein C caused by
      noncanonical cleavage at Arg46.
AB  - Activated protein C (APC) exerts endothelial cytoprotective actions that require
      protease-activated receptor 1 (PAR1), whereas thrombin acting via PAR1 causes
      endothelial disruptive, proinflammatory actions. APC's activities, but not
      thrombin's, require PAR1 located in caveolae. PAR1 is a biased 7-transmembrane
      receptor because G proteins mediate thrombin's signaling, whereas beta-arrestin 2
      mediates APC's signaling. Here we elucidate novel mechanisms for APC's initiation
      of signaling. Biochemical studies of APC's protease specificity showed that APC
      cleaved PAR1 sequences at both Arg41 and Arg46. That PAR1 cleavage at Arg46 can
      occur on cells was supported by APC's cleavage of N-terminal-SEAP-tagged R41Q
      PAR1 but not R41Q/R46Q-PAR1 mutants transfected into cells and by anti-PAR1
      epitope mapping of APC-treated endothelial cells. A synthetic peptide composing
      PAR1 residues 47-66, TR47, stimulated protective signaling in endothelial cells
      as reflected in Akt and glycogen synthase kinase 3beta phosphorylation, Ras
      related C3 botulinum toxin substrate 1 activation, and barrier stabilization
      effects. In mice, the TR47 peptide reduced VEGF-induced vascular leakage. These
      in vitro and in vivo data imply that the novel PAR1 N-terminus beginning at
      residue Asn47, which is generated by APC cleavage at Arg46, mediates APC's
      cytoprotective signaling and that this unique APC-generated N-terminal peptide
      tail is a novel biased agonist for PAR1.

PMID- 23149850
TI  - A systematic review of microvascular invasion in hepatocellular carcinoma:
      diagnostic and prognostic variability.
AB  - Selected patients with hepatocellular carcinoma are candidates to receive
      potentially curative treatments, such as hepatic resection or liver
      transplantation, but nevertheless there is a high risk of tumor recurrence.
      Microvascular invasion is a histological feature of hepatocellular carcinoma
      related to aggressive biological behavior. We systematically reviewed 20
      observational studies that addressed the prognostic impact of microvascular
      invasion, either after liver transplantation or resection. Outcomes were disease
      free survival and overall survival. In liver transplantation, the presence of
      microvascular invasion shortened disease-free survival at 3 years (relative risk
      (RR)=3.41 [2.05-5.7]; five studies, n=651) and overall survival both at 3 years
      (RR=2.41 [1.72-3.37]; five studies, n=1,938) and 5 years (RR=2.29 [1.85-2.83];
      six studies, n=2,003). After liver resection, microvascular invasion impacted
      disease-free survival at 3 and 5 years (RR=1.82 [1.61-2.07] and RR=1.51 [1.29
      1.77]; four studies, n=1,501 for both comparisons). However inter/intraobserver
      variability in reporting and the lack of definition and grading of microvascular
      invasion has led to great heterogeneity in evaluating this histological feature
      in hepatocellular carcinoma. Thus, there is an urgent need to clarify this issue,
      because determining prognosis and response to therapy have become important in
      the current management of hepatocellular carcinoma. In this systematic review, we
      summarize the diagnostic and prognostic data concerning microvascular invasion in
      hepatocellular carcinoma and present a basis for consensus on its definition.

PMID- 23149852
TI  - The current role of surgery in metastatic spine disease: a new era.

PMID- 23149851
TI  - Outcome and status of microsatellite stability in Japanese atomic bomb survivors
      with early gastric carcinoma.
AB  - BACKGROUND: In the decade after the 1945 atomic bombing of Hiroshima, a high
      incidence of leukemia was observed among atomic bomb survivors. However, the
      incidence of other cancers gradually increased, while that of leukemia decreased
      after this period. We evaluated the clinical outcome of early gastric cancer and
      microsatellite stability over a long-term period in atomic bomb survivors.
      METHODS: The results of surgical treatment for early gastric cancer were reviewed
      for 117 atomic bomb survivors and 394 control patients between 1995 and 2006. In
      addition, immunohistochemical staining for hMSH2 and hMLH1 expression was
      performed to evaluate the status of microsatellite stability in 57 atomic bomb
      survivors and 82 control patients. RESULTS: The long-term survival rate for early
      gastric cancer in atomic bomb survivors was significantly lower than that in
      control patients (p < 0.01). Multivariable analysis revealed that age and sex
      were significant and independent prognostic factors for early gastric cancer.
      Defective hMSH2 and/or hMLH1 expression was also significantly higher in
      survivors than in control patients (p < 0.001). Logistic regression analysis
      revealed that atomic bomb survivorship was related to defective hMSH2 and/or
      hMLH1 expression. CONCLUSIONS: The prognosis of early gastric cancer in atomic
      bomb survivors was poor and was related to age and sex, rather than to being an
      atomic bomb survivor. Furthermore, a higher rate of defective hMSH2 and/or hMLH1
      expression was observed in the survivors.

PMID- 23149853
TI  - Dosimetric feasibility and acute toxicity in a prospective trial of ultrashort
      course accelerated partial breast irradiation (APBI) using a multi-lumen balloon
      brachytherapy device.
AB  - BACKGROUND: Shorter courses of APBI, including single-fraction intraoperative
      therapy, are under active investigation. We designed a prospective trial to
      identify and address the potential radiobiological and logistical shortcomings of
      single-fraction APBI. METHODS: We designed a single-arm, multi-institutional,
      prospective phase II trial that sequentially treats 3 cohorts of women (each n =
      30) with 3 progressively hypofractionated schedules. Eligible women were age >=50
      years with unifocal invasive or in situ tumors <=3.0 cm, excised with negative
      margins, and with negative lymph nodes and positive hormone receptors. We defined
      strict dosimetric criteria for appropriateness. RESULTS: A total of 30 patients
      were enrolled at the 7 Gy * 4 fractions dose-level and followed for 6 months. The
      median skin dose as a percent of prescription dose (PD) was 84 % (40-100), and
      the median rib dose was 71 % (16-119). Also, 95 % of the PTV_eval received a
      median of 95 % of PD (range 85-103). The V150 (range 14-48 cc) and V200 (range 0
      29 cc) criteria were met in all cases. One breast infection occurred and was
      treated; 2 cases of symptomatic fat necrosis and 2 cases of symptomatic seromas
      occurred. CONCLUSION: Short-course APBI is dosimetrically feasible using the
      Contura MLB and appears to be tolerable in terms of acute toxicities. Our
      approach is based on well-defined radiobiological parameters and allows for an
      abbreviated course of treatment that is guided by full pathological review and
      the ability to objectively achieve and validate acceptable dosimetric criteria in
      each case. We have opened enrollment to the next schedule of 8.25 Gy for 3
      fractions.

PMID- 23149854
TI  - Seventh edition (2010) of the AJCC/UICC staging system for gastric
      adenocarcinoma: is there room for improvement?
AB  - BACKGROUND: The gastric cancer AJCC/UICC staging system recently underwent
      significant revisions, but studies on Asian patients have reported a lack of
      adequate discrimination between various consecutive stages. We sought to validate
      the new system on a U.S. population database. METHODS: California Cancer Registry
      data linked to the Office of Statewide Health Planning and Development discharge
      abstracts were used to identify patients with gastric adenocarcinoma
      (esophagogastric junction and gastric cardia tumors excluded) who underwent
      curative-intent surgical resection in California from 2002 to 2006. AJCC/UICC
      stage was recalculated based on the latest seventh edition. Overall survival
      probabilities were calculated using the Kaplan-Meier method. RESULTS: Of 1905
      patients analyzed, 54 % were males with a median age of 70 years. Median number
      of pathologically examined lymph nodes was 12 (range, 1-90); 40 % of patients
      received adjuvant chemotherapy, and 31 % received adjuvant radiotherapy. The
      seventh edition AJCC/UICC system did not distinguish outcome adequately between
      stages IB and IIA (P = 0.40), or IIB and IIIA (P = 0.34). By merging stage II
      into 1 category and moving T2N1 to stage IB and T2N2, T1N3 to stage IIIA, we
      propose a new grouping system with improved discriminatory ability CONCLUSIONS:
      In this first study validating the new seventh edition AJCC/UICC staging system
      for gastric cancer on a U.S. population with a relatively limited number of lymph
      nodes examined, we found stages IB and IIA, as well as IIB and IIIA to perform
      similarly. We propose a revised stage grouping for the AJCC/UICC staging system
      that better discriminates between outcomes.

PMID- 23149855
TI  - Drosophila SUUR protein associates with PCNA and binds chromatin in a cell cycle
      dependent manner.
AB  - Drosophila SUUR (Suppressor of UnderReplication) protein was shown to regulate
      the DNA replication elongation process in endocycling cells. This protein is also
      known to be the component of silent chromatin in polyploid and diploid cells. To
      mark the different cell cycle stages, we used immunostaining patterns of PCNA,
      the main structural component of replication fork. We demonstrate that SUUR
      chromatin binding is dynamic throughout the endocyle in Drosophila salivary
      glands. We observed that SUUR chromosomal localization changed along with PCNA
      pattern and these proteins largely co-localized during the late S-phase in
      salivary glands. The hypothesized interaction between SUUR and PCNA was confirmed
      by co-immunoprecipitation from embryonic nuclear extracts. Our findings support
      the idea that the effect of SUUR on replication elongation depends on the cell
      cycle stage and can be mediated through its physical interaction with replication
      fork.

PMID- 23149856
TI  - Repair of a critical-sized calvarial defect model using adipose-derived stromal
      cells harvested from lipoaspirate.
AB  - Craniofacial skeletal repair and regeneration offers the promise of de novo
      tissue formation through a cell-based approach utilizing stem cells. Adipose
      derived stromal cells (ASCs) have proven to be an abundant source of multipotent
      stem cells capable of undergoing osteogenic, chondrogenic, adipogenic, and
      myogenic differentiation. Many studies have explored the osteogenic potential of
      these cells in vivo with the use of various scaffolding biomaterials for cellular
      delivery. It has been demonstrated that by utilizing an osteoconductive,
      hydroxyapatite-coated poly(lactic-co-glycolic acid) (HA-PLGA) scaffold seeded
      with ASCs, a critical-sized calvarial defect, a defect that is defined by its
      inability to undergo spontaneous healing over the lifetime of the animal, can be
      effectively show robust osseous regeneration. This in vivo model demonstrates the
      basis of translational approaches aimed to regenerate the bone tissue - the
      cellular component and biological matrix. This method serves as a model for the
      ultimate clinical application of a progenitor cell towards the repair of a
      specific tissue defect.

PMID- 23149857
TI  - How parents make decisions to use medication to treat their child's ADHD: a
      grounded theory study.
AB  - BACKGROUND: Despite evidence of efficacy, a substantial percentage of children
      with attention deficit hyperactivity disorder (ADHD) either do not begin
      medication prescribed for their core symptoms or fail to continue treatment.
      OBJECTIVE: The purpose of this study was to understand (a) how parents decide to
      use medication to treat their child's ADHD and (b) the factors that influence
      their adherence to medication over time. DESIGN: Grounded theory guided data
      collection and analysis. Sixteen semistructured interviews with parents (13
      mothers, 3 fathers) of children with ADHD were conducted. RESULTS: The
      substantive theory developed from the data demonstrates that in seeking to help
      their child and restore a sense of stability around family life, parents engage
      in a process of "doing what helps most" in deciding to use medication to treat
      their child's ADHD. CONCLUSIONS: Interventions to support and guide parents
      throughout the decisional process are critical to meet the needs of families of
      children with ADHD.

PMID- 23149858
TI  - Angiostatic properties of sulindac and celecoxib in the experimentally induced
      inflammatory colorectal cancer.
AB  - Initiation of various cancers has been observed to be regulated via a prolonged
      inflammatory state in the tissues. However, molecular role of such a localized
      inflammation is not clear in the advanced stages of colorectal cancer. In this
      study, we have elaborated the role of various pro- and anti-inflammatory
      cytokines, transcription, and angiogenic factors in the progression of the 1,2
      dimethylhydrazine dihydrochloride (DMH)-induced late phage colorectal cancer and
      also observed the chemopreventive role of the two non-steroidal anti-inflammatory
      drugs (NSAIDs), viz., Sulindac and Celecoxib. Carcinogenic changes were observed
      with morphological and histopathological studies, whereas mRNA and protein
      regulations of various biomolecules were identified via RT- or qRT-PCR, western
      blot and immunofluorescence analysis, respectively. Activity of inducible nitric
      oxide (NO) and cyclooxygenase-2 enzymes were analyzed using standard NO assay and
      prostaglandin E2 immunoassay, whereas activities of matrix metalloproteinases
      (MMP-2 and-9) were identified by gelatin zymography. Flowcytometry was performed
      for the relative quantification of the apoptotic events. Molecular docking
      studies of Sulindac and Celecoxib were also performed with different target
      proteins to observe their putative mechanisms of action. As a result, we found
      that DMH-treated animals were having over-expression of various pro-inflammatory
      cytokines (IL-1beta, IL-2, and IFNgamma), aberrant nuclear localization of
      activated cell survival transcription factors (NF-kappaB and Stat3) along with
      the increased incidence of activated angiogenic factors (MMP-2 and MMP-9)
      suggesting a marked role of inflammation in the tumor progression. However,
      NSAIDs co-administration has significantly reduced the angiogenic potential of
      the growing neoplasm.

PMID- 23149859
TI  - Alpha-tocopheryl polyethylene glycol succinate-emulsified poly(lactic-co-glycolic
      acid) nanoparticles for reversal of multidrug resistance in vitro.
AB  - Multidrug resistance (MDR) is one of the factors in the failure of anticancer
      chemotherapy. In order to enhance the anticancer effect of P-glycoprotein (P-gp)
      substrates, inhibition of the P-gp efflux pump on MDR cells is a good tactic. We
      designed novel multifunctional drug-loaded alpha-tocopheryl polyethylene glycol
      succinate (TPGS)/poly(lactic-co-glycolic acid) (PLGA) nanoparticles (TPGS/PLGA/SN
      38 NPs; SN-38 is 7-ethyl-10-hydroxy-camptothecin), with TPGS-emulsified PLGA NPs
      as the carrier and modulator of the P-gp efflux pump and SN-38 as the model drug.
      TPGS/PLGA/SN-38 NPs were prepared using a modified solvent extraction/evaporation
      method. Physicochemical characterizations of TPGS/PLGA/SN-38 NPs were in
      conformity with the principle of nano-drug delivery systems (nDDSs), including a
      diameter of about 200 nm, excellent spherical particles with a smooth surface,
      narrow size distribution, appropriate surface charge, and successful drug-loading
      into the NPs. The cytotoxicity of TPGS/PLGA/SN-38 NPs to MDR cells was increased
      by 3.56 times compared with that of free SN-38. Based on an intracellular
      accumulation study relative to the time-dependent uptake and efflux inhibition,
      we suggest novel mechanisms of MDR reversal of TPGS/PLGA NPs. Firstly,
      TPGS/PLGA/SN-38 NPs improved the uptake of the loaded drug by clathrin-mediated
      endocytosis in the form of unbroken NPs. Simultaneously, intracellular NPs
      escaped the recognition of P-gp by MDR cells. After SN-38 was released from
      TPGS/PLGA/SN-38 NPs in MDR cells, TPGS or/and PLGA may modulate the efflux
      microenvironment of the P-gp pump, such as mitochondria and the P-gp domain with
      an ATP-binding site. Finally, the controlled-release drug entered the nucleus of
      the MDR cell to induce cytotoxicity. The present study showed that TPGS
      emulsified PLGA NPs could be functional carriers in nDDS for anticancer drugs
      that are also P-gp substrates. More importantly, to enhance the therapeutic
      effect of P-gp substrates, this work might provide a new insight into the design
      of pharmacologically inactive excipients that can serve as P-gp modulators
      instead of drugs that are P-gp inhibitors.

PMID- 23149860
TI  - Economics of the hydrolysis of cellulosic sludge to glucose.
AB  - Cellulosic sludge from paper mills making bleached products can be enzymatically
      converted to glucose. A kinetic model that accounts for product inhibition was
      used to estimate the cost:benefits of the process. In the proposed scheme, the
      sludge is enzymatically hydrolyzed in a sequence of CSTRs, the ash separated, and
      the product glucose concentrated through reverse osmosis. The water recovered is
      mostly recycled. By far, the most important economic variable is the value of the
      glucose. However, even if the glucose is assumed to be of no value the avoided
      cost of sludge disposal approximately offsets the process costs. The approach
      should generate significant revenue if the glucose is valued at market. 

PMID- 23149861
TI  - Nitrosonifedipine ameliorates angiotensin II-induced vascular remodeling via
      antioxidative effects.
AB  - Nifedipine is unstable under light and decomposes to a stable nitroso analog,
      nitrosonifedipine (NO-NIF). The ability of NO-NIF to block calcium channels is
      quite weak compared with that of nifedipine. Recently, we have demonstrated that
      NO-NIF reacts with unsaturated fatty acid leading to generate NO-NIF radical,
      which acquires radical scavenging activity. However, the effects of NO-NIF on the
      pathogenesis related with oxidative stress, such as atherosclerosis and
      hypertension, are unclear. In this study, we investigated the effects of NO-NIF
      on angiotensin II (Ang II)-induced vascular remodeling. Ang II-induced thickening
      and fibrosis of aorta were inhibited by NO-NIF in mice. NO-NIF decreased reactive
      oxygen species (ROS) in the aorta and urinary 8-hydroxy-20-deoxyguanosine. Ang II
      stimulated mRNA expressions of p22(phox), CD68, F4/80, monocyte chemoattractant
      protein-1, and collagen I in the aorta were inhibited by NO-NIF. Moreover, NO-NIF
      inhibited Ang II-induced cell migration and proliferation of vascular smooth
      muscle cells (VSMCs). NO-NIF reduced Ang II-induced ROS to the control level
      detected by dihydroethidium staining and lucigenin chemiluminescence assay in
      VSMCs. NO-NIF suppressed phosphorylations of Akt and epidermal growth factor
      receptor induced by Ang II. However, NO-NIF had no effects on intracellular
      Ca(2+) increase and protein kinase C-delta phosphorylation induced by Ang II in
      VSMCs. The electron paramagnetic resonance spectra indicated the continuous
      generation of NO-NIF radical of reaction with cultured VSMCs. These findings
      suggest that NO-NIF improves Ang II-induced vascular remodeling via the
      attenuation of oxidative stress.

PMID- 23149862
TI  - Racial differences in weight loss, payment method, and complications following
      Roux-en-Y gastric bypass and sleeve gastrectomy.
AB  - OBJECTIVES: Obesity affects approximately one-third of the US adult population.
      Although more black adults are considered to be obese compared to white adults,
      black adults are less likely to undergo bariatric surgery for weight loss. Black
      adults typically lose less weight and are more prone to adverse events following
      bariatric surgery than white adults. The objectives of this study were to compare
      weight loss, payment methods, and early postoperative complications between black
      and white adults. DESIGN: A retrospective chart review of 420 Roux-en-Y gastric
      bypass (RYGB) patients and 454 sleeve gastrectomy (SG) patients (all female) was
      conducted. A mixed-model analysis was used to assess statistical significance of
      differences in weight loss between surgeries and races. A Chi-square test was
      used to assess racial differences in payment method (insurance or private pay)
      and postoperative complications by operation. Statistical significance was set as
      P > 0.05. RESULTS: RYGB patients lost significantly more weight at 26, 52, 78,
      and 104 weeks postoperatively compared to SG patients. White females (WF) lost
      significantly more weight than black females (BF) at 26, 52, 78, and 104 weeks
      postoperatively. WF experienced more minor and major complications in the
      perioperative period than BF, but BF experienced more minor and overall
      complications in the postoperative period than WF. A greater percentage of black
      patients had insurance coverage compared to white patients for both surgeries.
      CONCLUSION: WF appear to lose more weight than BF regardless of surgery, but both
      races experience surgical complications. Black patients may be less likely to
      undergo bariatric surgery without insurance coverage.

PMID- 23149864
TI  - Association of estrogen with glucocorticoid levels in visceral fat in
      postmenopausal women.
AB  - OBJECTIVE: The aim of this study is to clarify the association between estrogen
      and glucocorticoid levels in adipose tissues of premenopausal and postmenopausal
      women. METHODS: Forty (15 premenopausal and 25 postmenopausal) women aged 22 to
      79 years were recruited through elective gynecological surgical operation, and
      both subcutaneous and visceral fat were collected during the surgical operation.
      Messenger RNA (mRNA) expressions of 11beta hydroxysteroid dehydrogenase type 1
      (HSD1), which catalyzes cortisone to cortisol, and 17beta-HSD1 and 17beta
      hydroxysteroid dehydrogenase type 2 (HSD2), which catalyze the interconversion of
      estrone (E1) and estradiol (E2), were measured by real-time reverse transcription
      polymerase chain reaction. The levels of E1, E2, cortisol, and cortisone in
      adipose tissues were measured by liquid chromatography tandem mass spectrometry.
      RESULTS: The visceral fat area was significantly increased (P < 0.01) in
      postmenopausal women compared with that in premenopausal women. The
      cortisol/cortisone ratio (P < 0.01) and the expression of 11beta-HSD1 mRNA (P <
      0.001) in visceral fat, but not in subcutaneous fat, in postmenopausal women were
      significantly higher than those in premenopausal women. There was a significant
      correlation (r = 0.69, P < 0.05) between the E1/E2 ratio of visceral fat and body
      mass index in postmenopausal women. A significant correlation (r = 0.54, P <
      0.05) between the cortisol/cortisone ratio and the E1/E2 ratio of visceral fat
      was observed in postmenopausal women. CONCLUSIONS: The expression of 11beta-HSD1
      mRNA in visceral fat increases in postmenopausal women, and the E1/E2 ratio in
      visceral fat may be associated with local glucocorticoid levels after menopause.

PMID- 23149866
TI  - Risk of metabolic syndrome in postmenopausal breast cancer survivors.
AB  - OBJECTIVE: The aim of this study was to assess the risk of metabolic syndrome
      (MetS) in postmenopausal breast cancer survivors as compared with postmenopausal
      women without breast cancer. METHODS: In this cross-sectional study, 104
      postmenopausal breast cancer survivors were compared with 208 postmenopausal
      women (controls) attending a university hospital. Eligibility criteria included
      the following: amenorrhea longer than 12 months and aged 45 years or older,
      treated for breast cancer, and metastasis-free for at least 5 years. The control
      group consisted of women with amenorrhea longer than 12 months and aged 45 years
      or older and without breast cancer, matched by age and menopause status (in a
      proportion of 1:2 as sample calculation). Clinical and anthropometric data were
      collected. Biochemical parameters, including total cholesterol, high-density
      lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides,
      glucose, and C-reactive protein, were measured. Women showing three or more
      diagnostic criteria were diagnosed as having MetS: waist circumference of 88 cm
      or larger, blood pressure of 130/85 mm Hg or higher, triglycerides level of 150
      mg/dL or higher, high-density lipoprotein cholesterol level lower than 50 mg/dL,
      and glucose level of 100 mg/dL or higher. For statistical analysis, Student's t
      test, chi2 test, and logistic regression (odds ratio [OR]) were used. RESULTS:
      The mean (SD) age of breast cancer survivors was 60.6 (8.6) years, with a mean
      (SD) follow-up of 9.4 (4.4) years. A higher percentage of breast cancer survivors
      (46.2%) were obese as compared with controls (32.7%; P < 0.05), and a smaller
      percentage showed optimal values for low-density lipoprotein cholesterol,
      glucose, and C-reactive protein versus controls (P < 0.05). MetS was diagnosed in
      50% of breast cancer survivors and in 37.5% of control group women (P < 0.05).
      Among the MetS diagnostic criteria, the most prevalent was abdominal obesity
      (waist circumference >88 cm), affecting 62.5% and 67.8% of the participants,
      respectively. In the control group, breast cancer survivors had a higher risk for
      MetS (OR, 1.66; 95% CI, 1.04-2.68), dysglycemia (OR, 1.05; 95% CI, 1.09-3.03),
      and hypertension (OR, 1.71; 95% CI, 1.02-2.89). CONCLUSIONS: Postmenopausal
      breast cancer survivors present a higher risk of developing MetS as compared with
      women without breast cancer.

PMID- 23149867
TI  - Effects of applied relaxation on vasomotor symptoms in postmenopausal women: a
      randomized controlled trial.
AB  - OBJECTIVE: This work aimed to study the efficacy of group therapy with applied
      relaxation on vasomotor symptoms and health-related quality of life in
      postmenopausal women. METHODS: In this open, randomized controlled trial, 60
      healthy postmenopausal women with at least seven moderate to severe hot flashes
      per 24 hours were randomized to either group therapy with applied relaxation (n =
      33) or untreated control group (n = 27) for 12 weeks. A follow-up visit was
      scheduled 3 months after the end of therapy or participation in the control
      group. Salivary cortisol was measured three times during a 6-month period. Hot
      flashes were recorded in self-registered diaries, and health-related quality of
      life was assessed with the Women's Health Questionnaire. RESULTS: The number of
      hot flashes decreased by 5.0 per 24 hours in the applied relaxation group
      compared with 1.9 in the control group on the 12th week (P < 0.001) and still
      remained at the same level at the 3-month follow-up (P < 0.001). Health-related
      quality of life for vasomotor symptoms, sleep, and memory improved significantly
      on the 12th week measurement in the applied relaxation group compared with the
      control group. Salivary cortisol concentration was lowered markedly in the
      applied relaxation group on a single measurement but was otherwise mainly stable
      in both groups. CONCLUSIONS: Applied relaxation can be used to treat vasomotor
      symptoms in healthy postmenopausal women.

PMID- 23149870
TI  - Do Italian surgeons use antibiotic prophylaxis in thyroid surgery? Results from a
      national study (UEC--Italian Endocrine Surgery Units Association).
AB  - Thyroid surgery is a clean procedure and therefore antibiotic prophylaxis is not
      routinely recommended by most international guidelines. However, antibiotics are
      often used in clinical practice. We enrolled 2926 patients who performed a
      thyroid surgical operation between the years 2009 and 2011 in the 38 centers of
      endocrine surgery that joined the UEC--Italian Endocrine Surgery Units
      Association. Antibiotic prophylaxis was used in 1132 interventions (38.7%). In
      case of antibiotic prophylaxis, cephalosporins or aminopenicillins +/- beta
      lactamase inhibitors were employed. At logistic regression analysis the use of
      drainage or device and the presence of malignancy were independent predictors of
      antibiotic prophylaxis employment. In conclusion our study shows that antibiotic
      prophylaxis was not rarely used in clinical practice in the setting of thyroid
      surgery. Drainage apposition, use of device, and malignant disease were
      independent predictors for antibiotic prophylaxis employment. More data on
      everyday practice and infection rate in well-designed studies are warranted to
      provide definitive recommendations on the utility of antibiotic prophylaxis in
      this setting. According to our experience, we don't consider to be strictly
      necessary the antibiotic prophylaxis employment in order to reduce infection rate
      in thyroid surgery.

PMID- 23149871
TI  - Safety, tolerability, pharmacokinetics and pharmacodynamics of single doses of
      empagliflozin, a sodium glucose cotransporter 2 (SGLT2) inhibitor, in healthy
      Japanese subjects.
AB  - This randomized, placebo-controlled within dose groups, double-blind, single
      rising dose study investigated the safety, tolerability, pharmacokinetics and
      pharmacodynamics of 1 mg to 100 mg doses of empagliflozin in 48 healthy Japanese
      male subjects. Empagliflozin was rapidly absorbed, reaching peak levels in 1.25
      to 2.50 h; thereafter, plasma concentrations declined in a biphasic fashion, with
      mean terminal elimination half-life ranging from 7.76 to 11.7 h. Increase in
      empagliflozin exposure was proportional to dose. Oral clearance was dose
      independent and ranged from 140 to 172 mL/min. In the 24 h following 100 mg
      empagliflozin administration, the mean (%CV) amount of glucose excreted in urine
      was 74.3 (17.1) g. The amount and the maximum rate of glucose excreted via urine
      increased with dose of empagliflozin. Nine adverse events, all of mild intensity,
      were reported by 8 subjects (7 with empagliflozin and 1 with the placebo). No
      hypoglycemia was reported. In conclusion, 1 mg to 100 mg doses of empagliflozin
      had a good safety and tolerability profile in healthy Japanese male subjects.
      Exposure to empagliflozin was dose proportional. The amount and rate of urinary
      glucose excretion were higher with empagliflozin than with the placebo, and
      increased with empagliflozin dose.

PMID- 23149872
TI  - Influence of SLCO1B3 genetic variations on tacrolimus pharmacokinetics in renal
      transplant recipients.
AB  - The immunosuppressive drug tacrolimus requires strict therapeutic monitoring due
      to its narrow therapeutic index and high interindividual variability. Organic
      anion transporting polypeptide 1B3 (OATP1B3) is a human hepatocyte transporter
      involved in the hepatobiliary elimination of diverse endogenous and exogenous
      substances. Genetic variations within the solute carrier (SLCO) 1B3 gene that
      encodes OATP1B3 may contribute to interindividual differences in tacrolimus
      disposition. The purpose of the present study is to investigate the association
      between SLCO1B3 polymorphisms and tacrolimus pharmacokinetics in renal transplant
      recipients. We found significant correlations between two linked coding
      nonsynomymous polymorphisms, T334G and G699A, and mean dose-adjusted tacrolimus
      trough blood concentrations during the first week post-transplantation (p = 0.04)
      and when the target dose (10-12 ng/ml) was obtained (p = 0.01). Patients carrying
      the homozygous mutant haplotype had 14.3-fold higher risk (95% confidence
      interval: 1.43-100; p = 0.02) of having blood tacrolimus concentrations above the
      median level, and thus being classified as poor OATP1B3 transporters, than
      carriers of one or two copies of the wild-type haplotype. This study shows, for
      the first time, that SLCO1B3 polymorphism is associated with tacrolimus exposure
      in the early post-transplant period.

PMID- 23149873
TI  - beta-hydroxy-beta-methylbutyrate did not enhance high intensity resistance
      training-induced improvements in myofiber dimensions and myogenic capacity in
      aged female rats.
AB  - Older women exhibit blunted skeletal muscle hypertrophy following resistance
      training (RT) compared to other age and gender cohorts that is partially due to
      an impaired regenerative capacity. In the present study, we examined whether beta
      hydroxy-beta-methylbutyrate (HMB) provision to aged female rodents would enhance
      regenerative mechanisms and facilitate RT-induced myofiber growth. Nineteen-month
      old female Sprague-Dawley rats were randomly divided into three groups: HMB (0.48
      g/kg/d; n = 6), non-HMB (n = 6), and control (n = 4). HMB and non-HMB groups
      underwent RT every third day for 10 weeks using a ladder climbing apparatus.
      Whole body strength, grip strength, and body composition was evaluated before and
      after RT. The gastrocnemius and soleus muscles were analyzed using magnetic
      resonance diffusion tensor imaging, RT-PCR, and immunohistochemistry to determine
      myofiber dimensions, transcript expression, and satellite cells/myonuclei,
      respectively. ANOVAs were used with significance set at p < 0.05. There were
      significant time effects (pre vs. post) for whole body strength (+262%), grip
      strength (+17%), lean mass (+20%), and fat mass (-19%). Both RT groups exhibited
      significant increases in the mean myofiber cross-sectional area (CSA) in the
      gastrocnemius and soleus (+8-22%) compared to control. Moreover, both groups
      demonstrated significant increases in the numbers of satellite cells (+100-108%)
      and myonuclei (+32%) in the soleus but not the gastrocnemius. A significant IGF-I
      mRNA elevation was only observed in soleus of the HMB group (+33%) whereas MGF
      and myogenin increased significantly in both groups (+32-40%). Our findings
      suggest that HMB did not further enhance intense RT-mediated myogenic mechanisms
      and myofiber CSA in aged female rats.

PMID- 23149874
TI  - Nicotine induces the expression of C-reactive protein via MAPK-dependent signal
      pathway in U937 macrophages.
AB  - Atherosclerosis is an inflammatory disease in the vessel wall. Nicotine, a major
      component of cigarette smoke, is an independent risk factor for cardiovascular
      diseases including atherosclerosis. As an inflammatory molecule, C- reactive
      protein (CRP) participates in atherogenesis. Although it has been confirmed that
      CRP level in smoking patient is significantly higher than non-smokers and
      cigarette withdrawal, it is unknown whether nicotine induces CRP expression in
      macrophages. The present study was to observe effect of nicotine on CRP
      production and the related signal pathway in U937 macrophages. The results showed
      that nicotine significantly increased mRNA and protein expression of CRP in U937
      macrophages in time- and concentration-dependent ways. Nicotinic acetylcholine
      receptor (nAChR) blocker hexamethonium, MEK1/2 inhibitor PD98059, p38 MAPK
      inhibitor SB203580 and NF-kappaB inhibitor PDTC almost completely abolished
      nicotineinduced CRP expression in mRNA and protein levels in U937 macrophages.
      The further study indicated that hexamethonium, PD98059, and SB203580
      significantly inhibited ERK1/2 and p38 MAPK phosphorylation. These demonstrate
      that nicotine has ability to induce CRP expression in macrophages through nAChR
      ERK1/2/p38 MAPK-NF-kappaB signal pathway, which contributes to better
      understanding of the pro-inflammatory and pro-atherosclerotic effects of nicotine
      in cigarette smokers.

PMID- 23149875
TI  - The association between difficulty using positive airway pressure equipment and
      adherence to therapy: a pilot study.
AB  - PURPOSE: Little is known about the ease of use of positive airway pressure (PAP)
      equipment and whether PAP equipment usability is associated with adherence. This
      pilot project aims to determine whether perceived difficulty with the mechanics
      of using PAP equipment is associated with nonadherence. METHODS: Within a larger
      study of insomnia treatments, we screened (via telephone interview) 148 adults
      for sleep apnea/prior PAP use and asked them to describe the degree of difficulty
      putting on their PAP mask, adjusting their mask straps, turning dials/pushing PAP
      machine buttons, disconnecting tubing, and removing the machine's water chamber
      (five items; five-point Likert-like scale) and to report their PAP use (0 versus
      >=1 days in the past week). RESULTS: Mean age of participants was 66.7 years (SD
      7.0). Thirty respondents (20.3 %) reported at least "some difficulty" with at
      least one aspect of PAP equipment usability, and 15 respondents (10.1 %) reported
      at least "quite a lot of difficulty" with one or more aspects of PAP equipment
      usability. Of the participants, 43.9 % reported not using PAP equipment at all
      during the past week. Participants (73.3 %) with substantial PAP equipment
      difficulty (at least quite a lot of difficulty) versus 40.6 % without substantial
      difficulty reported zero nights of PAP use in the past week (chi-square 5.86, p =
      .015). CONCLUSIONS: Difficulty using PAP equipment is associated with PAP
      nonadherence. Studies are needed to confirm these findings and to identify
      determinants of poor usability. If findings are confirmed, strategies could be
      developed to improve PAP usability, which may improve adherence.

PMID- 23149876
TI  - Reduced left atrial early strain rate following acute sleep deprivation: chance
      finding or chance to find out more on the conundrum of sleep and cardiovascular
      disease?

PMID- 23149877
TI  - Impact of type D personality on adherence to oral appliance therapy for sleep
      disordered breathing.
AB  - PURPOSE: Type D personality, defined as a combination of social inhibition and
      negative affectivity, has been associated with poor medication adherence and
      lower adherence to continuous positive airway pressure in patients with sleep
      disordered breathing. Up to this date, the association of patient's personality
      with adherence with a mandibular advancement device (MAD) has not been studied.
      The purposes of this study were to examine the association between type D
      personality and poor adherence to MAD treatment and to examine the impact of type
      D personality on perceived side effects during this treatment. METHODS: Eighty
      two patients out of 113 patients with a known baseline type D scale who have
      started MAD treatment between June 2006 and December 2009 were included.
      Information about side effects and adherence were collected via a postal
      questionnaire. Thirty-three patients were using a monobloc MAD and 49 patients
      were using a duobloc MAD. RESULTS: Forty-five percent of type D patients
      discontinued MAD treatment, whereas only 15 % of non-type D patients reported
      treatment discontinuation. The odds ratio for treatment discontinuation was 6.03
      (95 % confidence interval 1.22-29.81; p = 0.027) for type D personality, adjusted
      for age, gender, MAD type (monobloc or duobloc), and decrease in apnea severity.
      In continuing MAD users, no significant difference in perceived side effects was
      reported between the personality types. CONCLUSION: This is the first study to
      examine the relationship between type D personality and adherence to MAD
      treatment. Type D patients reported a significantly higher discontinuation rate
      when compared to patients without type D personality.

PMID- 23149878
TI  - Urea cycle defects and hyperammonemia: effects on functional imaging.
AB  - The urea-cycle disorders (UCDs) are a group of congenital enzyme and carrier
      deficiencies predisposing to hyperammonemia (HA). HA causes changes in the
      central nervous system (CNS) including alterations of neurotransmitter function,
      cell volume, and energy deprivation ultimately leading to cerebral edema.
      Neuropathological findings of UCDs primarily reflect changes in astrocyte
      morphology. Neurological features accompanying acute HA include changes in
      behavior and consciousness in the short term, and potential for impairments in
      memory and executive function as long-term effects. Plasma measures of ammonia
      and glutamine, although useful for clinical monitoring, prove poor markers of CNS
      function. Multimodal neuroimaging has potential to investigate impact on
      cognitive function by interrogating neural networks, connectivity and
      biochemistry. As neuroimaging methods become increasingly sophisticated, they
      will play a critical role in clinical monitoring and treatment of metabolic
      disease. We describe our findings in UCDs; with focus on Ornithine
      Transcarbamylase deficiency (OTCD) the only X linked UCD.

PMID- 23149879
TI  - Mammalian glutaminase isozymes in brain.
AB  - Glutamine/glutamate homeostasis must be exquisitely regulated in mammalian brain
      and glutaminase (GA, E.C. 3.5.1.2) is one of the main enzymes involved. The
      products of GA reaction, glutamate and ammonia, are essential metabolites for
      energy and biosynthetic purposes but they are also hazardous compounds at
      concentrations beyond their normal physiological thresholds. The classical
      pattern of GA expression in mammals has been recently challenged by the discovery
      of novel transcript variants and protein isoforms. Furthermore, the interactome
      of brain GA is also starting to be uncovered adding a new level of regulatory
      complexity. GA may traffic in brain and unexpected locations, like cytosol and
      nucleus, have been found for GA isoforms. Finally, the expression of GA in glial
      cells has been reported and its potential implications in ammonia homeostasis are
      discussed.

PMID- 23149880
TI  - [Preclinical treatment of severe burn trauma due to an electric arc on an
      overhead railway cable].
AB  - Severe burns due to electrical accidents occur rarely in Germany but represent a
      challenge for emergency physicians and their team. Apart from extensive burns
      cardiac arrhythmia, neurological damage caused by electric current and osseous
      injury corresponding to the trauma mechanism are also common. It is important to
      perform a survey of the pattern of injuries and treat acute life-threatening
      conditions immediately in the field. Furthermore, specific conditions related to
      burns must be considered, e.g. fluid resuscitation, thermal management and
      analgesia. In addition, a correct strategy for further medical care in an
      appropriate hospital is essential. Exemplified by this case guidelines for the
      treatment of severe burns and typical pitfalls are presented. 

PMID- 23149881
TI  - [Percutaneous stabilization of thoracolumbar fractures. Techniques of fracture
      reduction and spinal cord decompression].
AB  - Minimally invasive percutaneous instrumentations are increasingly being used for
      stabilization of thoracolumbar fractures, mainly due to the advantages of reduced
      soft tissue damage. While percutaneous instrumentation can be generally used in
      less displaced fractures, it remains controversial whether such techniques should
      also be performed in patients with severe fracture dislocation. This includes
      patients with severe traumatic kyphosis and/or dislocation in the coronar plane,
      particularly in concomitant neurological deficits that require additional
      decompression surgery. Here we show the different indirect fracture reduction
      techniques in three cases with severe fracture dislocation and discuss the use of
      percutaneous stabilization techniques in combination with an additional midline
      approach for decompressing laminectomy. 

PMID- 23149882
TI  - [Pediatric calcaneal fracture after supination trauma: conservative therapy with
      an orthosis].
AB  - We report the case of a 12-year-old boy with a calcaneal fracture due to a simple
      supination trauma. As magnetic resonance imaging (MRI) showed a non-displaced
      extra-articular fracture no surgical treatment was necessary. A conservative
      therapy using calcaneal fracture orthosis with full weight bearing was carried
      out. Using this procedure allowed a comfortable means of movement without the
      need for a plaster cast immobilization or forearm crutches accompanied by a rapid
      return of the child to the normal daily routine. 

PMID- 23149883
TI  - Amino-acid-based, lipid-directed, in situ synthesis and fabrication of gold
      nanoparticles on silica: a metamaterial framework with pronounced catalytic
      activity.
AB  - We introduce a new example of the in situ preparation and fabrication of stable
      gold nanoparticles on silica in an aqueous medium, by using only lipid-grafted
      silica particles in HAuCl(4) solution without addition of any external reducing
      agent. The lipid-grafted silica particles have been synthesized by graft-to
      methodology and characterized by elemental analysis, thermogravimetric analysis
      and Fourier-transform infrared spectroscopy. The metamaterial particles show high
      catalytic activity for the reduction of p-nitrophenol to p-aminophenol.

PMID- 23149884
TI  - Mobility and storage sinks for chromium and other metals in soils impacted by
      leather tannery wastes.
AB  - Leather tanneries around the world, including China, introduce chromium (Cr) and
      other metals into the environment. In China, the population pressure compels the
      utilization of every piece of available land for food production. In this study,
      we investigated the content, leachability and possible storage sinks for Cr and
      other metals in soils around facilities of leather industry in southern China. It
      was found that Cr in soils impacted by tannery can be as high as 2484 mg Cr kg-1
      soil, and the mean contents of other metals such as Zn (214 mg Zn kg-1 soil), Cd
      (5.4 mg Cd kg-1 soil), As (17 mg As kg-1 soil) exceeded the soil quality
      standards and guidelines in China and Canada. Simulated leaching studies (i.e.,
      Synthetic Precipitation Leaching Procedure) indicated that these soils could
      release Cr and other metals in concentrations above the environmental quality
      guidelines and standards for water in China and Canada. As a result, the mobility
      of metals from these soils can potentially contaminate both groundwater and
      surface water. We also found differential leachability of metals with soil
      properties such as total metal and total carbon contents. Principal component
      analysis of the total contents of 32 elements showed that the possible major
      sinks for Cr are organic matter and oxides of Fe/Mn/Al, while sulfates and
      phosphates are potential storage of Cd, Zn, Cu and Pb. The information obtained
      from this study can be valuable for the restoration of ecosystem functions (i.e.,
      food production) in the study area.

PMID- 23149885
TI  - Photodynamic therapy in dermatology: past, present, and future.
AB  - Photodynamic therapy (PDT) is a noninvasive therapeutic method first introduced
      in the field of dermatology. It is mainly used for the treatment of precancerous
      and superficial malignant skin tumors. Today PDT finds new applications not only
      for nononcologic dermatoses but also in the field of other medical specialties
      such as otorhinolaryngology, ophthalmology, neurology, gastroenterology, and
      urology. We are witnessing a broadening of the spectrum of skin diseases that are
      treated by PDT. Since its introduction, PDT protocol has evolved significantly in
      terms of increasing method efficacy and patient safety. In this era of evidence
      based medicine, it is expected that much effort will be put into creating a
      worldwide accepted consensus on PDT. A review on the current knowledge of PDT is
      given, and the historical basis of the method's evolution since its introduction
      in the 1900s is presented. At the end, future challenges of PDT are focused on
      discussing gaps that exist for research in the field.

PMID- 23149887
TI  - Understandable and not surprising.

PMID- 23149886
TI  - Gender differences in the diagnostic accuracy of SPECT myocardial perfusion
      imaging: a bivariate meta-analysis.
AB  - BACKGROUND: It remains controversial whether the diagnostic accuracy of single
      photon emission computed tomography myocardial perfusion imaging (SPECT MPI) is
      different in men as compared to women. We performed a meta-analysis to
      investigate gender differences of SPECT MPI for the diagnosis of CAD (>=50%
      stenosis). METHOD: Two investigators independently performed a systematic review
      of the MEDLINE and EMBASE databases from inception through January 2012 for
      English-language studies determining the diagnostic accuracy of SPECT MPI. We
      included prospective studies that compared SPECT MPI with conventional coronary
      angiography which provided sufficient data to calculate gender-specific true and
      false positives and negatives. Data from studies evaluating <20 patients of one
      gender were excluded. Bivariate meta-analysis was used to create summary receiver
      operating curves. RESULTS: Twenty-six studies met inclusion criteria,
      representing 1,148 women and 1,142 men. Bivariate meta-analysis yielded a mean
      sensitivity and specificity of 84.2% (95% confidence interval [CI] 78.7%-88.6%)
      and 78.7% (CI 70.0%-85.3%) for SPECT MPI in women and 89.1% (CI 84.0%-92.7%) and
      71.2% (CI 60.8%-79.8%) for SPECT MPI in men. There was no significant difference
      in the sensitivity (P = .15) or specificity (P = .23) between male and female
      subjects. CONCLUSION: In a bivariate meta-analysis of the available literature,
      the diagnostic accuracy of SPECT MPI is similar for both men and women.

PMID- 23149888
TI  - The clinical evaluation of novel imaging methods for cancer management.
AB  - The National Cancer Institute (NCI) has a long-standing interest in evaluating
      and using the known advantages of molecular and functional imaging, as well as
      assessing the potential of novel imaging agents and modalities, to improve
      clinical cancer research and cancer care. In this Perspectives article, I discuss
      the strategies and resources being used by the NCI to foster and enhance these
      evaluations. Although resource and logistical challenges abound in successfully
      mounting these trials, many examples exist of real and potential solutions to
      improve the clinical evaluation process for imaging agents and modalities in the
      USA and in international collaborations.

PMID- 23149889
TI  - Abiraterone and its place in the treatment of metastatic CRPC.
AB  - An update of the COU-AA-301 study confirms a survival advantage with abiraterone
      prednisone compared to prednisone in post-docetaxel patients with metastatic
      castration-resistant prostate cancer. We place these data in the context of
      earlier disease states and other novel agents and explore practical issues
      concerning the future use of abiraterone.

PMID- 23149890
TI  - Imaging. Response in follicular lymphoma can be assessed using PET.

PMID- 23149891
TI  - Palliative care. Chemotherapy and hope of cancer cure: dying expectations.

PMID- 23149892
TI  - Imaging in oncology--over a century of advances.
AB  - Over the past 120 years, the discipline of oncology has evolved so that a
      multitude of anatomical and increasingly complex functional imaging techniques
      are now applicable in both clinical and research platforms. This Timeline article
      revisits the achievements of the pioneer techniques in cancer imaging, discusses
      how these techniques have changed over time, provides some examples of clinical
      importance, and ventures to explain how imaging will remodel the future of modern
      oncology.

PMID- 23149893
TI  - Imaging hypoxia to improve radiotherapy outcome.
AB  - Reduced oxygen levels (hypoxia) is one of the most important factors influencing
      clinical outcome after radiotherapy. This is primarily because hypoxic cells are
      resistant to radiation treatment; hence, the greater the number of clonogenic
      cancer stem cells that exist under hypoxia, the lower the local tumour control.
      Reduced local control will influence overall survival, as may the hypoxic
      conditions by increasing malignant progression; however, to fight hypoxia, we
      should first be able to see it. We need noninvasive approaches that can
      accurately and reliably image hypoxia in tumours, especially using techniques
      that are routinely available in the clinic, such as PET, MRI and CT. All these
      imaging methods are already under clinical evaluation in this context. Such data
      should allow us to identify those patients on an individual basis who have
      hypoxic tumours and, thus, at the very least should receive some form of hypoxic
      modifier in conjunction with radiotherapy. Alternatively, the radiation dose
      could be either increased to the whole tumour or, if the imaging is accurate
      enough, only to the hypoxic subvolumes. The aim of this Review is to critically
      assess the potential use of imaging to help improve clinical outcome to
      radiotherapy.

PMID- 23149895
TI  - Metastasis. Landscaping brain metastasis therapy.

PMID- 23149894
TI  - Functional imaging in adult and paediatric brain tumours.
AB  - Imaging is a key component in the management of brain tumours, with MRI being the
      preferred modality for most clinical scenarios. However, although conventional
      MRI provides mainly structural information, such as tumour size and location, it
      leaves many important clinical questions, such as tumour type, aggressiveness and
      prognosis, unanswered. An increasing number of studies have shown that additional
      information can be obtained using functional imaging methods (which probe tissue
      properties), and that these techniques can give key information of clinical
      importance. These techniques include diffusion imaging, which can assess tissue
      structure, and perfusion imaging and magnetic resonance spectroscopy, which
      measures tissue metabolite profiles. Tumour metabolism can also be investigated
      using PET, with 18F-deoxyglucose being the most readily available tracer. This
      Review discusses these methods and the studies that have investigated their
      clinical use. A strong emphasis is placed on the measurement of quantitative
      parameters, which is a move away from the qualitative nature of conventional
      radiological reporting and presents major challenges, particularly for
      multicentre studies.

PMID- 23149897
TI  - Chemotherapy. Intensified therapy for Ewing sarcoma.

PMID- 23149896
TI  - Is there still a role for SPECT-CT in oncology in the PET-CT era?
AB  - For the evaluation of biological processes using radioisotopes, there are two
      competing technologies: single-photon emission computed tomography (SPECT) and
      positron emission tomography (PET). Both are tomographic techniques that enable
      3D localization and can be combined with CT for hybrid imaging. PET-CT has clear
      technical superiority including superior resolution, speed and quantitative
      capability. SPECT-CT currently has greater accessibility, lower cost and
      availability of a wider range of approved radiotracers. However, the past decade
      has seen dramatic growth in PET-CT with decreasing costs and development of an
      increasing array of PET tracers that can substitute existing SPECT applications.
      PET-CT is also changing the paradigm of imaging from lesion measurement to lesion
      characterization and target quantification, supporting a new era of personalized
      cancer therapy. The efficiency and cost savings associated with improved
      diagnosis and clinical decision-making provided by PET-CT make a cogent argument
      for it becoming the dominant molecular technique in oncology.

PMID- 23149898
TI  - Ziv-aflibercept: binding to more than VEGF-A--does more matter?
AB  - The VELOUR and VITAL studies recently demonstrated ziv-aflibercept improved
      overall survival in patients with metastatic colorectal cancer (mCRC), including
      those previously treated with bevacizumab, but did not improve overall survival
      in non-small-cell lung cancer. Thus, VEGF-directed agents might be useful
      throughout the continuum of care in mCRC, but biomarkers are needed to identify
      patients likely to benefit.

PMID- 23149899
TI  - Brain cancer. Fine-tuning chemoradiotherapy for anaplastic oligodendroglioma.

PMID- 23149901
TI  - Comparison of non-invasive methods for measurement of local pulse wave velocity
      using FSI-simulations and in vivo data.
AB  - In the search for better predictors of cardiovascular events, pulse wave velocity
      (PWV) has gained considerable interest. We compared three single-location methods
      to locally estimate PWV based on simultaneous measurements of pressure (P),
      velocity (U) or arterial diameter (D): the PU, ln(D)U and QA-method. First, the
      performance of these methods was analyzed using 3D fluid-structure interaction
      simulations (FSI) in a tube and patient-specific carotid artery. We demonstrated
      that the outcome was dependent on whether the methods were tested in the ideal
      conditions of a 3D axisymmetrical and reflection-free tube or in the more
      realistic setup of a carotid artery. The three single-location PWV methods
      performed similarly in the tube (4.29 m/s for PU, 4.44 m/s for ln(D)U and 4.38
      m/s for QA) while the carotid data showed that the PU-method dramatically
      overestimates PWV (9.16 m/s), and the ln(D)U and QA-method underestimate (3.86
      and 3.84 m/s, respectively). The erroneously high wavespeeds from the PU-method
      were attributed to wave reflections, which was confirmed by measurements in 37
      healthy adults. This in vivo study showed similar discrepancies between the 3
      single-location techniques as present in the carotid simulations, with the
      difference between the PU- and ln(D)U-method related to the magnitude of wave
      reflection.

PMID- 23149900
TI  - First all-in-one diagnostic tool for DNA intelligence: genome-wide inference of
      biogeographic ancestry, appearance, relatedness, and sex with the Identitas v1
      Forensic Chip.
AB  - When a forensic DNA sample cannot be associated directly with a previously
      genotyped reference sample by standard short tandem repeat profiling, the
      investigation required for identifying perpetrators, victims, or missing persons
      can be both costly and time consuming. Here, we describe the outcome of a
      collaborative study using the Identitas Version 1 (v1) Forensic Chip, the first
      commercially available all-in-one tool dedicated to the concept of developing
      intelligence leads based on DNA. The chip allows parallel interrogation of
      201,173 genome-wide autosomal, X-chromosomal, Y-chromosomal, and mitochondrial
      single nucleotide polymorphisms for inference of biogeographic ancestry,
      appearance, relatedness, and sex. The first assessment of the chip's performance
      was carried out on 3,196 blinded DNA samples of varying quantities and qualities,
      covering a wide range of biogeographic origin and eye/hair coloration as well as
      variation in relatedness and sex. Overall, 95 % of the samples (N = 3,034) passed
      quality checks with an overall genotype call rate >90 % on variable numbers of
      available recorded trait information. Predictions of sex, direct match, and first
      to third degree relatedness were highly accurate. Chip-based predictions of
      biparental continental ancestry were on average ~94 % correct (further support
      provided by separately inferred patrilineal and matrilineal ancestry).
      Predictions of eye color were 85 % correct for brown and 70 % correct for blue
      eyes, and predictions of hair color were 72 % for brown, 63 % for blond, 58 % for
      black, and 48 % for red hair. From the 5 % of samples (N = 162) with <90 % call
      rate, 56 % yielded correct continental ancestry predictions while 7 % yielded
      sufficient genotypes to allow hair and eye color prediction. Our results
      demonstrate that the Identitas v1 Forensic Chip holds great promise for a wide
      range of applications including criminal investigations, missing person
      investigations, and for national security purposes.

PMID- 23149902
TI  - Temporal healing in rat achilles tendon: ultrasound correlations.
AB  - The purpose of this study was to explore whether a new ultrasound-based technique
      correlates with mechanical and biological metrics that describe the tendon
      healing. Achilles tendons in 32 rats were unilaterally transected and allowed to
      heal without repair. At 7, 9, 14, or 29 days post-injury, tendons were collected
      and examined for healing via ultrasound image analysis, mechanical testing, and
      immunohistochemistry. Consistent with previous studies, we observe that the
      healing tendons are mechanically inferior (ultimate stress, ultimate load, and
      normalized stiffness) and biologically altered (cellular and ECM factors)
      compared to contralateral controls with an incomplete recovery over healing time.
      Unique to this study, we report: (1) Echo intensity (defined by gray-scale
      brightness in the ultrasound image) in the healing tissue is related to stress
      and normalized stiffness. (2) Elongation to failure is relatively constant so
      that tissue normalized stiffness is linearly correlated with ultimate stress.
      Together, 1 and 2 suggest a method to quantify mechanical compromise in healing
      tendons. (3) The amount and type of collagen in healing tendons associates with
      their strength and normalized stiffness as well as their ultrasound echo
      intensity. (4) A significant increase of periostin in the healing tissues
      suggests an important but unexplored role for this ECM protein in tendon healing.

PMID- 23149903
TI  - Respiratory flow-sound relationship during both wakefulness and sleep and its
      variation in relation to sleep apnea.
AB  - Tracheal respiratory sound analysis is a simple and non-invasive way to study the
      pathophysiology of the upper airway and has recently been used for acoustic
      estimation of respiratory flow and sleep apnea diagnosis. However in none of the
      previous studies was the respiratory flow-sound relationship studied in people
      with obstructive sleep apnea (OSA), nor during sleep. In this study, we recorded
      tracheal sound, respiratory flow, and head position from eight non-OSA and 10 OSA
      individuals during sleep and wakefulness. We compared the flow-sound relationship
      and variations in model parameters from wakefulness to sleep within and between
      the two groups. The results show that during both wakefulness and sleep, flow
      sound relationship follows a power law but with different parameters.
      Furthermore, the variations in model parameters may be representative of the OSA
      pathology. The other objective of this study was to examine the accuracy of
      respiratory flow estimation algorithms during sleep: we investigated two
      approaches for calibrating the model parameters using the known data recorded
      during either wakefulness or sleep. The results show that the acoustical
      respiratory flow estimation parameters change from wakefulness to sleep.
      Therefore, if the model is calibrated using wakefulness data, although the
      estimated respiratory flow follows the relative variations of the real flow, the
      quantitative flow estimation error would be high during sleep. On the other hand,
      when the calibration parameters are extracted from tracheal sound and respiratory
      flow recordings during sleep, the respiratory flow estimation error is less than
      10%.

PMID- 23149904
TI  - Magnetic nanoparticle targeted hyperthermia of cutaneous Staphylococcus aureus
      infection.
AB  - The incidence of wound infections that do not adequately respond to standard-of
      care antimicrobial treatment has been increasing. To address this challenge, a
      novel antimicrobial magnetic thermotherapy platform has been developed in which a
      high-amplitude, high-frequency, alternating magnetic field is used to rapidly
      heat magnetic nanoparticles that are bound to Staphylococcus aureus (S. aureus).
      The antimicrobial efficacy of this platform was evaluated in the treatment of
      both an in vitro culture model of S. aureus biofilm and a mouse model of
      cutaneous S. aureus infection. We demonstrated that an antibody-targeted magnetic
      nanoparticle bound to S. aureus was effective at thermally inactivating S. aureus
      and achieving accelerated wound healing without causing tissue injury.

PMID- 23149905
TI  - New-onset multiple sclerosis associated with adalimumab treatment in rheumatoid
      arthritis: a case report and literature review.
AB  - Tumor necrosis factor (TNF) antagonists have brought about a significant
      advancement in treatment for autoimmune diseases such as rheumatoid arthritis
      (RA) and Crohn's disease; however, they are accompanied with a risk of severe
      adverse effects. We report the case of a 68-year-old female with a 33-year
      history of RA that developed multiple sclerosis (MS) during adalimumab (ADM)
      treatment at 22 months after the initial administration. Her first neurological
      symptom was mild dizziness, which progressed to severe dizziness with gait
      disturbance within 2 weeks. Fortunately, when she had this neurological disorder,
      ADM treatment was being transiently stopped because she was in the perioperative
      period. Repeated magnetic resonance imaging examinations revealed multiple
      demyelinating lesions in her brain, leading to the diagnosis of MS. The patient
      completely recovered spontaneously from the symptoms in several days. A review of
      the literature revealed another 15 cases of MS associated with anti-TNF-alpha
      treatment, emphasizing the importance of detecting neurological symptoms and
      discontinuing the anti-TNF-alpha therapy.

PMID- 23149906
TI  - Well-being outcomes of chiropractic intervention for lower back pain: a
      systematic review.
AB  - The usefulness of chiropractic for treatment of low back pain is a contentious
      issue. Chiropractors advocate holism and general well-being as a key principle on
      which they base their clinical practice, yet the quality of life, lifestyle,
      health and economic impacts of chiropractic intervention for back pain in adults
      have rarely been investigated. This article provides an overview of chiropractic
      principles and practices, together with the results of a systematic review of
      peer-reviewed publications between 2000 and 2010 retrieved from MEDLINE, CINAHL,
      EMBASE, AMED and Cochrane Database of Systematic Reviews. This review sought to
      determine the benefits of chiropractic treatment and care to well-being, and to
      what extent chiropractic treatment and care improve quality of life. Of 1,165
      articles, 12 articles were retained, representing six studies (four randomised
      controlled trial, two observational) of varying quality. There was a high degree
      of inconsistency and lack of standardisation in measurement instruments and
      outcome measures. Three studies reported reduced use of other/extra treatments as
      a positive outcome; two studies reported a positive effect of chiropractic
      intervention on pain, and two studies reported a positive effect on disability.
      The six studies reviewed concentrated on the impact of chiropractic care on
      physical health and disability, rather than the wider holistic view which was the
      focus of this study. It is difficult, therefore, to defend any conclusion about
      the impact of chiropractic intervention on the quality of life, lifestyle, health
      and economic impact on chiropractic patients presenting with back pain.

PMID- 23149907
TI  - High throughput sequential ELISA for validation of biomarkers of acute graft
      versus-host disease.
AB  - Unbiased discovery proteomics strategies have the potential to identify large
      numbers of novel biomarkers that can improve diagnostic and prognostic testing in
      a clinical setting and may help guide therapeutic interventions. When large
      numbers of candidate proteins are identified, it may be difficult to validate
      candidate biomarkers in a timely and efficient fashion from patient plasma
      samples that are event-driven, of finite volume and irreplaceable, such as at the
      onset of acute graft-versus-host disease (GVHD), a potentially life-threatening
      complication of allogeneic hematopoietic stem cell transplantation (HSCT). Here
      we describe the process of performing commercially available ELISAs for six
      validated GVHD proteins: IL-2Ralpha(5), TNFR1(6), HGF(7), IL-8(8), elafin(2), and
      REG3alpha(3) (also known as PAP1) in a sequential fashion to minimize freeze-thaw
      cycles, thawed plasma time and plasma usage. For this procedure we perform the
      ELISAs in sequential order as determined by sample dilution factor as established
      in our laboratory using manufacturer ELISA kits and protocols with minor
      adjustments to facilitate optimal sequential ELISA performance. The resulting
      plasma biomarker concentrations can then be compiled and analyzed for significant
      findings within a patient cohort. While these biomarkers are currently for
      research purposes only, their incorporation into clinical care is currently being
      investigated in clinical trials. This technique can be applied to perform ELISAs
      for multiple proteins/cytokines of interest on the same sample(s) provided the
      samples do not need to be mixed with other reagents. If ELISA kits do not come
      with pre-coated plates, 96-well half-well plates or 384-well plates can be used
      to further minimize use of samples/reagents.

PMID- 23149908
TI  - QT dispersion in patients with acromegaly.
AB  - Acromegaly is a rare condition caused by a pituitary adenoma that secretes growth
      hormone. The mortality rate is 72 % higher in patients with acromegaly than in
      the general population according to meta-analyses. Mortality analysis has shown
      as many as 60 % of acromegalic patients die due to cardiovascular disease. Sudden
      cardiac death may occur in patients with acromegaly and malignant ventricular
      arrhythmia may play an important role in this fatal complication; however, the
      precise mechanism is not fully known. QT dispersion (dQT) is an
      electrophysiological factor known to be associated with a tendency for
      ventricular arrhythmia and sudden cardiac death. This study aimed to evaluate dQT
      as an early predictor of ventricular tachyarrhythmia, as sudden cardiac death
      commonly occurs in acromegalic patients. This cross-sectional case-control study
      enrolled 20 patients (10 female and 10 male) with acromegaly and 20 healthy
      controls (11 female and 9 male) after exclusion criteria were applied. Each
      participant underwent 12-lead electrocardiography, including >=3 QRS complexes,
      at a speed of 25 mm/s after a 15-min rest. In each participant, the QT interval
      (beginning of the Q wave to the end of the T wave) was corrected (QTc) for heart
      rate using Bazett's formula [Formula: see text] QTc dispersion (dQTc) (QTc max -
      QTc min) was also calculated. There was no significant difference in median dQTc
      between the acromegalic patients (0.79 s) and the controls (0.45 s) (p > 0.05).
      Active acromegalic patients (n = 14) were estimated to have a median dQTc of 0.82
      s, after excluding from the analysis six patients that were under full
      biochemical control, and that had randomly obtained growth hormone levels <0.4
      ng/mL, GH <1 ng/mL based on oral glucose tolerance test, and normal IGF-I for age
      and gender. A significant difference was noted in median dQTc between the active
      acromegalic patients and the controls (p = 0.015). The dQT in active acromegalic
      patients was longer than that in the control group, which indicates that patients
      with active acromegaly might have an elevated risk for ventricular arrhythmia. We
      think that a non-invasive, simple and inexpensive marker-measurement of dQT-as
      part of cardiac monitoring could be valuable for screening complications in
      acromegalic patients.

PMID- 23149909
TI  - Hypothalamic neuropeptide S receptor blockade decreases discriminative cue
      induced reinstatement of cocaine seeking in the rat.
AB  - RATIONALE: Previous studies have shown that activation of brain neuropeptide S
      receptor (NPSR) facilitates reinstatement of cocaine seeking elicited by
      environmental cues predictive of drug availability. This finding suggests the
      possibility that blockade of NPSR receptors may be of therapeutic benefit in
      cocaine addiction. To evaluate this hypothesis, we investigated the effect of two
      newly synthetized NPSR antagonists, namely the quinolinone-amide derivative NPSR
      QA1 and the NPS peptidic analogue [D-Cys(tBu)5]NPS on cocaine self-administration
      and on discriminative cue-induced relapse to cocaine seeking in the rat. METHODS:
      Separate groups of rats self-administered food and cocaine 0.25 mg/kg/inf in FR1
      and FR5 (fixed ratio reinforcement schedules) for 30-min and 2-h sessions per
      day. After food and cocaine intake reached baseline levels, the effect of NPSR
      QA1 was tested on cocaine and food self-administration. The NPSR-QA1 was injected
      intraperitoneally and its effect on discriminative cue-induced reinstatement was
      evaluated, while [D-Cys(tBut)5]NPS was injected intracranially, intra-lateral
      hypothalamus, intra-perifornical area of the hypothalamus, and intra-central
      amygdala. The effect of the NPSR-QA1 on extinction of cocaine seeking was also
      assessed. RESULTS: Intraperitoneal administration of NPSR-QA1 (15-30 mg/kg) did
      not affect cocaine self-administration. Conversely, NPSR-QA1 (15-30 mg/kg)
      decreased discriminative cue-induced cocaine relapse. At the lowest dose, this
      effect was specific, while at the highest dose, NPSR-QA1 also reduced food self
      administration. The efficacy of NPSR antagonism on cocaine seeking was confirmed
      with [D-Cys(tBu)5]NPS (10-30 nmol/rat) as it markedly inhibited relapse behavior
      following site-specific injection into the lateral hypothalamus and the
      perifornical area of the hypothalamus but not into the central amygdala.
      CONCLUSIONS: The identification of the NPS/NPSR system as an important new
      element involved in the physiopathology of cocaine addiction and the discovery of
      the anti-addictive properties of NPSR antagonists opens the possibility of
      exploring a new mechanism for cocaine addiction treatment.

PMID- 23149910
TI  - [Academic journals: print or online?].

PMID- 23149911
TI  - RNA trafficking by acute myelogenous leukemia exosomes.
AB  - Extrinsic signaling cues in the microenvironment of acute myelogenous leukemia
      (AML) contribute to disease progression and therapy resistance. Yet, it remains
      unknown how the bone marrow niche in which AML arises is subverted to support
      leukemic persistence at the expense of homeostatic function. Exosomes are cell
      membrane-derived vesicles carrying protein and RNA cargoes that have emerged as
      mediators of cell-cell communication. In this study, we examined the role of
      exosomes in developing the AML niche of the bone marrow microenvironment,
      investigating their biogenesis with a focus on RNA trafficking. We found that
      both primary AML and AML cell lines released exosome-sized vesicles that entered
      bystander cells. These exosomes were enriched for several coding and noncoding
      RNAs relevant to AML pathogenesis. Furthermore, their uptake by bone marrow
      stromal cells altered their secretion of growth factors. Proof-of-concept studies
      provided additional evidence for the canonical functions of the transferred RNA.
      Taken together, our findings revealed that AML exosome trafficking alters the
      proliferative, angiogenic, and migratory responses of cocultured stromal and
      hematopoietic progenitor cell lines, helping explain how the microenvironmental
      niche becomes reprogrammed during invasion of the bone marrow by AML.

PMID- 23149912
TI  - DNA damage-specific control of cell death by cryptochrome in p53-mutant ras
      transformed cells.
AB  - The main feedback loop driving circadian rhythm in mice is controlled, in part,
      by the genes encoding the cryptochromes Cry1 and Cry2. Targeted mutation of both
      Cry1 and Cry2 delay the early onset of tumor formation in p53-null mutant mice.
      Furthermore, Ras-transformed p53- and Cry-null mouse skin fibroblasts are more
      sensitive than p53 mutants to apoptotic cell death initiated by agents that
      activate either the intrinsic or the extrinsic apoptosis pathways. Here, we
      investigated the effect of Cry1 and Cry2 mutations on cell death by other
      genotoxic agents that generate alkylated bases, interstrand crosslinks, DNA
      protein crosslinks, and double-strand breaks. Both ultraviolet (UV) and the UV
      mimetic compound oxaliplatin and the radiomimetic compound doxorubicin promoted
      apoptosis by upregulating the tumor suppressor p73. However, only the UV and
      oxaliplatin-induced upregulation of p73 mediated by the transcription factor
      Egr1, but not the doxorubicin-induced upregulation mediated by the transcription
      factor E2F1, was enhanced by Cry1/Cry2 double mutation. Accordingly, Egr1
      downregulation reduced oxaliplatin-induced apoptosis, whereas E2F1 downregulation
      reduced doxorubicin-induced apoptosis. Our findings establish distinct roles for
      cryptochromes in intrinsic apoptosis induced by UV mimetic and radiomimetic
      agents.

PMID- 23149913
TI  - Autophagy control by the VEGF-C/NRP-2 axis in cancer and its implication for
      treatment resistance.
AB  - A major contributor to cancer mortality is recurrence and subsequent metastatic
      transformation following therapeutic intervention. Therefore, in order to develop
      new treatment modalities and improve the efficacy of current ones, it is
      important to understand the molecular mechanisms that promote resistance to
      therapy in cancer cells. One pathway contributing to therapy resistance is
      autophagy, a self-digestive process that can eliminate unnecessary or damaged
      organelles to protect cancer cells from death. We have found that the VEGF-C/NRP
      2 axis is involved in the activation of autophagy, which helps cancer cell
      survival following treatment. Inhibition of mTOR complex 1 activity by this axis
      is the underlying mechanism for the activation of autophagy. Furthermore, we
      identified two VEGF-C/NRP-2-regulated genes, LAMP-2 and WDFY-1, that have
      previously been suggested to participate in autophagy and vesicular trafficking.
      Upregulation of WDFY-1 following VEGF-C or NRP-2 depletion contributes to
      cytotoxic drug-mediated cell death. Together, these data suggest a link between
      the VEGF-C/NRP-2 axis and cancer cell survival despite the presence of
      chemotherapy-induced stress. Effective targeting of this pathway may lead to the
      development of new cancer therapies.

PMID- 23149915
TI  - Bcl3 selectively promotes metastasis of ERBB2-driven mammary tumors.
AB  - Bcl3 is a putative proto-oncogene deregulated in hematopoietic and solid tumors.
      Studies in cell lines suggest that its oncogenic effects are mediated through the
      induction of proliferation and inhibition of cell death, yet its role in
      endogenous solid tumors has not been established. Here, we address the oncogenic
      effect of Bcl3 in vivo and describe how this Stat3-responsive oncogene promotes
      metastasis of ErbB2-positive mammary tumors without affecting primary tumor
      growth or normal mammary function. Deletion of the Bcl3 gene in ErbB2-positive
      (MMTV-Neu) mice resulted in a 75% reduction in metastatic tumor burden in the
      lungs with a 3.6-fold decrease in cell turnover index in these secondary lesions
      with no significant effect on primary mammary tumor growth, cyclin D1 levels, or
      caspase-3 activity. Direct inhibition of Bcl3 by siRNA in a transplantation model
      of an Erbb2-positive mammary tumor cell line confirmed the effect of Bcl3 in
      malignancy, suggesting that the effect of Bcl3 was intrinsic to the tumor cells.
      Bcl3 knockdown resulted in a 61% decrease in tumor cell motility and a
      concomitant increase in the cell migration inhibitors Nme1, Nme2, and Nme3, the
      GDP dissociation inhibitor Arhgdib, and the metalloprotease inhibitors Timp1 and
      Timp2. Independent knockdown of Nme1, Nme2, and Arhgdib partially rescued the
      Bcl3 motility phenotype. These results indicate for the first time a cell
      autonomous disease-modifying role for Bcl3 in vivo, affecting metastatic disease
      progression rather than primary tumor growth.

PMID- 23149914
TI  - Common single-nucleotide polymorphisms in the estrogen receptor beta promoter are
      associated with colorectal cancer survival in postmenopausal women.
AB  - Loss of estrogen receptor beta (ERbeta) expression in the gut is associated with
      colorectal cancer (CRC) initiation and progression. Germline single-nucleotide
      polymorphisms (SNP) in genes for the sex-steroid hormone receptors are not
      strongly associated with CRC risk; however, these SNPs have not previously been
      evaluated in relation to survival after diagnosis. We enrolled 729 women, ages 50
      to 74, diagnosed with invasive CRC between 1997 and 2002 in 13 counties covered
      by the Seattle-Puget Sound Surveillance Epidemiology and End Results cancer
      registry. Participants provided germline DNA. We selected 99 tag-SNPs for the
      androgen receptor (AR), ERalpha (ESR1), ERbeta (ESR2), and progesterone receptor
      (PGR) genes. Mortality outcomes were ascertained from the National Death Index.
      During a median of 6.6 years of follow-up, 244 deaths occurred (161 from CRC). We
      identified 20 SNPs (12 of ESR2 and 8 of PGR) for replication in 1,729 women
      diagnosed with incident invasive CRC (555 deaths; 405 from CRC) from three
      prospective cohort studies that participate in the Genetics and Epidemiology of
      Colorectal Cancer Consortium. Three correlated SNPs in the promoter of ESR2
      (rs2987983, rs3020443, and rs2978381) were statistically significant predictors
      of CRC-specific and overall survival. Minor alleles of each were associated with
      improved survival [for rs2987983, CRC-specific HR, 0.77; 95% confidence interval
      (CI), 0.60-0.99 in the initial study, and HR, 0.79; CI, 0.64-0.98 in
      replication]. No associations were noted for SNPs of AR, ESR1, or PGR. SNPs in
      the promoter of ESR2 may be important to pathways related to the association
      between ERbeta and tumor progression and metastasis.

PMID- 23149917
TI  - Angiopoietin-2 functions as a Tie2 agonist in tumor models, where it limits the
      effects of VEGF inhibition.
AB  - The angiopoietins Ang1 (ANGPT1) and Ang2 (ANGPT2) are secreted factors that bind
      to the endothelial cell-specific receptor tyrosine kinase Tie2 (TEK) and regulate
      angiogenesis. Ang1 activates Tie2 to promote blood vessel maturation and
      stabilization. In contrast, Ang2, which is highly expressed by tumor endothelial
      cells, is thought to inhibit Tie2 activity and destabilize blood vessels, thereby
      facilitating VEGF-dependent vessel growth. Here, we show that the inhibition of
      tumor xenograft growth caused by an Ang2-specific antibody (REGN910) is reversed
      by systemic administration of the Tie2 agonist Ang1. These results indicate that
      Ang2 blockade inhibits tumor growth by decreasing Tie2 activity, showing that
      Ang2 is a Tie2 activator. REGN910 treatment of tumors resulted in increased
      expression of genes that are repressed by Tie2 activation, providing further
      evidence that REGN910 inhibits Tie2 signaling. Combination treatment with REGN910
      plus the VEGF blocker aflibercept reduced tumor vascularity and tumor perfusion
      more dramatically than either single agent, resulting in more extensive tumor
      cell death and more potent inhibition of tumor growth. Challenging the prevailing
      model of Ang2 as a destabilizing factor, our findings indicate that Ang2 plays a
      protective role in tumor endothelial cells by activating Tie2, thereby limiting
      the antivascular effects of VEGF inhibition. Thus, blockade of Ang2 might enhance
      the clinical benefits currently provided by anti-VEGF agents. .

PMID- 23149916
TI  - Tasquinimod Is an Allosteric Modulator of HDAC4 survival signaling within the
      compromised cancer microenvironment.
AB  - Tasquinimod is an orally active antiangiogenic drug that is currently in phase
      III clinical trials for the treatment of castration-resistant prostate cancer.
      However, the target of this drug has remained unclear. In this study, we applied
      diverse strategies to identify the histone deacetylase HDAC4 as a target for the
      antiangiogenic activity of tasquinimod. Our comprehensive analysis revealed
      allosteric binding (Kd 10-30 nmol/L) to the regulatory Zn(2+) binding domain of
      HDAC4 that locks the protein in a conformation preventing HDAC4/N-CoR/HDAC3
      complex formation. This binding inhibited colocalization of N-CoR/HDAC3, thereby
      inhibiting deacetylation of histones and HDAC4 client transcription factors, such
      as HIF-1alpha, which are bound at promoter/enhancers where epigenetic
      reprogramming is required for cancer cell survival and angiogenic response.
      Through this mechanism, tasquinimod is effective as a monotherapeutic agent
      against human prostate, breast, bladder, and colon tumor xenografts, where its
      efficacy could be further enhanced in combination with a targeted thapsigargin
      prodrug (G202) that selectively kills tumor endothelial cells. Together, our
      findings define a mechanism of action of tasquinimod and offer a perspective on
      how its clinical activity might be leveraged in combination with other drugs that
      target the tumor microenvironment. Cancer Res; 73(4); 1386-99. (c)2012 AACR.

PMID- 23149918
TI  - mTOR inhibitor RAD001 promotes metastasis in a rat model of pancreatic
      neuroendocrine cancer.
AB  - Inhibition of mTOR is commonly considered a valid target in cancer treatment, but
      this assertion does not address effects on the immune microenvironment that may
      be detrimental to cancer treatment. Here we show how administration of the mTOR
      inhibitor RAD001 (everolimus) results in the occurrence of distant metastasis in
      a rat model of pancreatic cancer. RAD001 was administered twice weekly for 4.5
      weeks as a single treatment or combined with [(177)Lu-DOTA,Tyr3]octreotate
      ((177)Lu-DOTATATE), where the latter targets the somatostatin receptor-2. The
      hypothesized synergistic therapeutic effect of RAD001 combined with (177)Lu
      DOTATATE was, however, not observed in our experiments. The combination was shown
      to be less effective than (177)Lu-DOTATATE alone. Unexpectedly, tumor metastasis
      was observed in 77% of the subjects treated with RAD001, either alone or as part
      of the combination treatment. This was a striking effect, because metastasis did
      not occur in control or (177)Lu-DOTATATE-treated animals, including those where
      the primary tumor was surgically removed. These findings may be important
      clinically among noncompliant patients or patients that discontinue RAD001
      therapy because of adverse effects.

PMID- 23149919
TI  - Antitumor immunotherapeutic and toxic properties of an HDL-conjugated chimeric IL
      15 fusion protein.
AB  - Interleukin (IL)-15 effects on CD8 T and natural killer (NK) lymphocytes hold
      promise to treat cancer. Fusion proteins have been engineered to provide IL-15
      receptor alpha (IL-15Ralpha) mediated trans-presentation to lymphocytes and
      extend the plasma half-life of the cytokine. In this study, we report on a triple
      fusion protein combining apolipoprotein A-I (Apo A-I), IL-15, and IL-15Ralpha's
      sushi domain. Apo A-I conveys IL-15 to high-density lipoproteins (HDL), from
      which the cytokine is trans-presented by the IL-15Ralpha's sushi domain. Such a
      construction was tested by hydrodynamic gene transfer to the liver of mice.
      Lethal toxicity was observed upon injection of 10 MUg of the expression plasmid.
      Mice died from an acute lymphocytic pneumonitis in which T and NK cells dominate
      a severe inflammatory infiltrate. Importantly, mice devoid of NK cells were not
      susceptible to such toxicity and mice lacking granzymes A and B also survived the
      otherwise lethal gene transfer. Lower plasmid doses (<2.5 MUg) were tolerated and
      dramatically increased the numbers of NK and memory CD8 T lymphocytes in the
      liver, spleen, and lungs, to the point of rescuing the deficiency of such
      lymphocyte subsets in IL-15Ralpha(-/-) mice. Doses of plasmid within the
      therapeutic window successfully treated metastatic tumor models, including B16OVA
      lung metastasis of melanoma and MC38 colon cancer liver metastasis. Sushi-IL-15
      Apo as a recombinant protein was also bioactive in vivo, became conjugated to
      HDL, and displayed immunotherapeutic effects against metastatic disease.

PMID- 23149920
TI  - Definition of molecular determinants of prostate cancer cell bone extravasation.
AB  - Advanced prostate cancer commonly metastasizes to bone, but transit of malignant
      cells across the bone marrow endothelium (BMEC) remains a poorly understood step
      in metastasis. Prostate cancer cells roll on E-selectin(+) BMEC through E
      selectin ligand-binding interactions under shear flow, and prostate cancer cells
      exhibit firm adhesion to BMEC via beta1, beta4, and alphaVbeta3 integrins in
      static assays. However, whether these discrete prostate cancer cell-BMEC adhesive
      contacts culminate in cooperative, step-wise transendothelial migration into bone
      is not known. Here, we describe how metastatic prostate cancer cells breach BMEC
      monolayers in a step-wise fashion under physiologic hemodynamic flow. Prostate
      cancer cells tethered and rolled on BMEC and then firmly adhered to and traversed
      BMEC via sequential dependence on E-selectin ligands and beta1 and alphaVbeta3
      integrins. Expression analysis in human metastatic prostate cancer tissue
      revealed that beta1 was markedly upregulated compared with expression of other
      beta subunits. Prostate cancer cell breaching was regulated by Rac1 and Rap1
      GTPases and, notably, did not require exogenous chemokines as beta1, alphaVbeta3,
      Rac1, and Rap1 were constitutively active. In homing studies, prostate cancer
      cell trafficking to murine femurs was dependent on E-selectin ligand, beta1
      integrin, and Rac1. Moreover, eliminating E-selectin ligand-synthesizing alpha1,3
      fucosyltransferases in transgenic adenoma of mouse prostate mice dramatically
      reduced prostate cancer incidence. These results unify the requirement for E
      selectin ligands, alpha1,3 fucosyltransferases, beta1 and alphaVbeta3 integrins,
      and Rac/Rap1 GTPases in mediating prostate cancer cell homing and entry into bone
      and offer new insight into the role of alpha1,3 fucosylation in prostate cancer
      development.

PMID- 23149922
TI  - MIG-7 controls COX-2/PGE2-mediated lung cancer metastasis.
AB  - More effective treatments for metastatic lung cancer remain a pressing clinical
      need. In this study, we identified migration inducting gene-7 (MIG-7) protein as
      critical for COX-2/prostaglandin E2 (PGE2)- and Akt/GSK-3beta-dependent tumor
      invasion/metastasis. COX-2/PGE2 activated EP4 to enhance Akt and GSK-3beta
      phosphorylation and beta-catenin/T-cell factor/lymphoid enhancer factor signaling
      leading to MIG-7 upregulation. RNAi-mediated attenuation of MIG-7 blocked COX
      2/PGE2- and Akt/GSK-3beta-mediated migration/invasion effects. Furthermore, MIG-7
      protein inhibited protein phosphatase 2A to sustain Akt/GSK-3beta phosphorylation
      and cancer-cell migration/invasion. Cancer cells overexpressing MIG-7 exhibited
      increased expression of ZEB-1 and Twist in parallel with epithelial-mesenchymal
      transition, metastasis and cancer lethality. MIG-7 protein level positively
      correlated with advanced stages of human lung cancers. MIG-7 thus offers a
      theranostic target for cancer metastases arising from aberrant activation of the
      cellular COX-2/PGE2 and Akt/GSK-3beta signaling pathways.

PMID- 23149921
TI  - STAT5 is crucial to maintain leukemic stem cells in acute myelogenous leukemias
      induced by MOZ-TIF2.
AB  - MOZ-TIF2 is a leukemogenic fusion oncoprotein that confers self-renewal
      capability to hematopoietic progenitor cells and induces acute myelogenous
      leukemia (AML) with long latency in bone marrow transplantation assays. Here, we
      report that FLT3-ITD transforms hematopoietic cells in cooperation with MOZ-TIF2
      in vitro and in vivo. Coexpression of FLT3-ITD confers growth factor independent
      survival/proliferation, shortens disease latency, and results in an increase in
      the number of leukemic stem cells (LSC). We show that STAT5, a major effector of
      aberrant FLT3-ITD signal transduction, is both necessary and sufficient for this
      cooperative effect. In addition, STAT5 signaling is essential for MOZ-TIF2
      induced leukemic transformation itself. Lack of STAT5 in fetal liver cells caused
      rapid differentiation and loss of replating capacity of MOZ-TIF2-transduced cells
      enriched for LSCs. Furthermore, mice serially transplanted with Stat5(-/-) MOZ
      TIF2 leukemic cells develop AML with longer disease latency and finally
      incomplete penetrance when compared with mice transplanted with Stat5(+/+) MOZ
      TIF2 leukemic cells. These data suggest that STAT5AB is required for the self
      renewal of LSCs and represents a combined signaling node of FLT3-ITD and MOZ-TIF2
      driven leukemogenesis. Therefore, targeting aberrantly activated STAT5 or rewired
      downstream signaling pathways may be a promising therapeutic option.

PMID- 23149924
TI  - Up to date service evaluations and needs assessments would be useful in caring
      for elderly prisoners.

PMID- 23149925
TI  - Restoration impact of an uncontrolled phosphogypsum dump site on the seasonal
      distribution of abiotic variables, phytoplankton and zooplankton along the near
      shore of the south-western Mediterranean coast.
AB  - 'In connection with the Taparura Project, we studied the distribution of
      phytoplankton and zooplankton communities in relation to environmental variables
      at 18 stations sampled during four coastal cruises conducted between October 2009
      and July 2010 on the north coast of Sfax (Tunisia, western Mediterranean Sea).
      The inshore location was largely dominated by diatoms (66 %) represented
      essentially by members of the genera Navicula, Grammatophora, and Licmophora.
      Dinophyceae were numerically the second largest group and showed an enhanced
      species richness. Cyanobacteriae developed in association with an important
      proliferation of colonial Trichodesmium erythraeum, contributing 39.4 % of total
      phytoplankton abundances. The results suggest that phytoplankters are generally
      adapted to specific environmental conditions. Copepods were the most abundant
      zooplankton group (82 %) of total zooplankton. A total of 21 copepod species were
      identified in all stations, with an overwhelming abundance of Oithona similis in
      autumn and summer, Euterpina acutifrons in winter, and Oncaea conifera in spring.
      The phosphogypsum restoration had been acutely necessary allowing dominant
      zooplankton species to exploit a wide range of food resources including
      phytoplankton and thus improving water quality.

PMID- 23149926
TI  - Transperitoneal laparoscopic adrenalectomy. Our experience.
AB  - AIM: Laparoscopic adrenalectomy is considered the standard technique for the
      surgical removal of the adrenal gland. This report is about a 4-year single
      experience in our Endocrine and General Surgery Unit with laparoscopic
      adrenalectomy. METHODS: A total of 24 lateral transperitoneal laparoscopic
      adrenalectomies were performed. The indications for laparoscopic surgery were:
      aldosteronoma in 3 patients, pheochromocytoma in 6 patients, nonfunctioning
      adenoma in 6 patients, adenoma causing Cushing's syndrome in 3 patients, 1
      lymphangioma-like adenomatoid tumor, 1 myelolipoma, 1 complicated adrenal cyst, 2
      adrenocortical carcinomas, 1 lung metastasis. RESULTS: All except two had
      successful laparoscopic adrenalectomy. Complication occurred in one patient. 3
      patients underwent other associated laparoscopic procedures. Operative time
      ranged from 100 to 240 minutes for laparoscopic adrenalectomy, from 180 to 210
      minutes in the cases with two associated laparoscopic procedures, 5 hours for
      bilateral adrenalectomy; the postoperative hospital stay for laparoscopic
      adrenalectomy ranged from 4 to 8 days (6,79 days) and from 7 to 13 days (9,12
      days) for patients undergoing the open or converted procedure. CONCLUSIONS:
      Laparoscopic adrenalectomy is technically feasible and reproducible. We evaluate
      the effectiveness of laparoscopic adrenalectomy for a variety of endocrine
      disorders except in the case of invasive carcinoma or large masses. Antonio
      Cardarelli Endocrine and General Surgery Unit in Naples is known as a specialized
      center for thyroid and parathyroid surgery; in future, we could also become a
      high-volume laparoscopic referral center for adrenal gland pathologies.

PMID- 23149927
TI  - Longitudinal cystic fibrosis care.
AB  - Cystic fibrosis is a complex disease entity that presents considerable lifelong
      challenges. Implementation of medical and surgical treatment options involves
      multisystem interventions to prevent and treat lung and gastrointestinal
      manifestations of cystic fibrosis and associated comorbidities. From birth
      through adulthood, cystic fibrosis care entails a longitudinal regimen aimed at
      achieving relief of disease symptoms and enhanced life expectancy. With increased
      knowledge of the molecular behavior of the cystic fibrosis transmembrane
      conductance regulator (CFTR) in health and disease, clinical practice has been
      enriched by the prospect of novel strategies, including mutation-specific drug
      and gene therapy targeting restoration of corrupted transepithelial ion
      transport. Emerging paradigms of comprehensive care increasingly enable
      personalized solutions to address the root cause of disease-transforming
      management options for individuals with cystic fibrosis.

PMID- 23149928
TI  - CYP2B6 and bupropion's smoking-cessation pharmacology: the role of
      hydroxybupropion.
AB  - Bupropion is indicated to promote smoking cessation. Animal studies suggest that
      the pharmacologic activity of bupropion can be mediated by its major metabolite,
      hydroxybupropion. We measured plasma bupropion and its metabolite levels in a
      double-blind, placebo controlled, randomized smoking-cessation trial. Among the
      treatment-adherent individuals, higher hydroxybupropion concentrations (per
      MUg/ml) resulted in better smoking-cessation outcomes (week 3, 7, and 26 odds
      ratio (OR) = 2.82, 2.96, and 2.37, respectively, P = 0.005-0.040); this was not
      observed with bupropion levels (OR = 1.00-1.03, P = 0.59-0.90). Genetic variation
      in CYP2B6, the enzyme that metabolizes bupropion to hydroxybupropion, was
      identified as a significant source of variability in hydroxybupropion formation.
      Our data indicate that hydroxybupropion contributes to the pharmacologic effects
      of bupropion for smoking cessation, and that variability in response to bupropion
      treatment is related to variability in CYP2B6-mediated hydroxybupropion
      formation. These findings suggest that dosing of bupropion to achieve a
      hydroxybupropion level of 0.7 MUg/ml or increasing bupropion dose for CYP2B6 slow
      metabolizers could improve bupropion's cessation outcomes.

PMID- 23149929
TI  - Proarrhythmic safety of repeat doses of mirabegron in healthy subjects: a
      randomized, double-blind, placebo-, and active-controlled thorough QT study.
AB  - Potential effects of the selective beta(3)-adrenoceptor agonist mirabegron on
      cardiac repolarization were studied in healthy subjects. The four-arm, parallel,
      two-way crossover study was double-blind and placebo- and active (moxifloxacin)
      controlled. After 2 baseline ECG days, subjects were randomized to one of eight
      treatment sequences (22 females and 22 males per sequence) of placebo crossed
      over with once-daily (10 days) 50, 100, or 200 mg mirabegron or a single 400-mg
      moxifloxacin dose on day 10. In each period, continuous ECGs were recorded at two
      baselines and on the last drug administration day. The lower one-sided 95%
      confidence interval for moxifloxacin effect on QTcI was >5 ms, demonstrating
      assay sensitivity. According to ICH E14 criteria, mirabegron did not cause QTcI
      prolongation at the 50-mg therapeutic and 100-mg supratherapeutic doses in either
      sex. Mirabegron prolonged QTcI interval at the 200-mg supratherapeutic dose
      (upper one-sided 95% CI >10 ms) in females, but not in males.

PMID- 23149930
TI  - Beeping and piping: characterization of two mechano-acoustic signals used by
      honey bees in swarming.
AB  - Of the many signals used by honey bees during the process of swarming, two of
      them--the stop signal and the worker piping signal--are not easily distinguished
      for both are mechano-acoustic signals produced by scout bees who press their
      bodies against other bees while vibrating their wing muscles. To clarify the
      acoustic differences between these two signals, we recorded both signals from the
      same swarm and at the same time, and compared them in terms of signal duration,
      fundamental frequency, and frequency modulation. Stop signals and worker piping
      signals differ in all three variables: duration, 174 +/- 64 vs. 602 +/- 377 ms;
      fundamental frequency, 407 vs. 451 Hz; and frequency modulation, absent vs.
      present. While it remains unclear which differences the bees use to distinguish
      the two signals, it is clear that they do so for the signals have opposite
      effects. Stop signals cause inhibition of actively dancing scout bees whereas
      piping signals cause excitation of quietly resting non-scout bees.

PMID- 23149931
TI  - Mechanistic modelling of cancer: some reflections from software engineering and
      philosophy of science.
AB  - There is a growing interest in mathematical mechanistic modelling as a promising
      strategy for understanding tumour progression. This approach is accompanied by a
      methodological change of making research, in which models help to actively
      generate hypotheses instead of waiting for general principles to become apparent
      once sufficient data are accumulated. This paper applies recent research from
      philosophy of science to uncover three important problems of mechanistic
      modelling which may compromise its mainstream application, namely: the dilemma of
      formal and informal descriptions, the need to express degrees of confidence and
      the need of an argumentation framework. We report experience and research on
      similar problems from software engineering and provide evidence that the
      solutions adopted there can be transferred to the biological domain. We hope this
      paper can provoke new opportunities for further and profitable interdisciplinary
      research in the field.

PMID- 23149932
TI  - Hexagonal comb cells of honeybees are not produced via a liquid equilibrium
      process.
AB  - The nests of European honeybees (Apis mellifera) are organised into wax combs
      that contain many cells with a hexagonal structure. Many previous studies on comb
      building behaviour have been made in order to understand how bees produce this
      geometrical structure; however, it still remains a mystery. Direct construction
      of hexagons by bees was suggested previously, while a recent hypothesis
      postulated the self-organised construction of hexagonal comb cell arrays;
      however, infrared and thermographic video observations of comb building in the
      present study failed to support the self-organisation hypothesis because bees
      were shown to be engaged in direct construction. Bees used their antennae,
      mandibles and legs in a regular sequence to manipulate the wax, while some bees
      supported their work by actively warming the wax. During the construction of
      hexagonal cells, the wax temperature was between 33.6 and 37.6  degrees C. This
      is well below 40  degrees C, i.e. the temperature at which wax is assumed to
      exist in the liquid equilibrium that is essential for self-organised building.

PMID- 23149933
TI  - Oxidized DJ-1 inhibits p53 by sequestering p53 from promoters in a DNA-binding
      affinity-dependent manner.
AB  - DJ-1 is an oncogene and the causative gene for familial Parkinson's disease.
      Although the oxidative status of DJ-1 at cysteine 106 (C106) is thought to affect
      all of the activities of DJ-1 and excess oxidation leads to the onset of various
      diseases, the precise molecular mechanisms underlying the effects of oxidation of
      DJ-1 on protein-protein interactions of DJ-1 remain unclear. In this study, we
      found that DJ-1 bound to the DNA-binding region of p53 in a manner dependent on
      the oxidation of C106. Of the p53 target genes, the expression level and promoter
      activity of the DUSP1 gene, but not those of the p21 gene, were increased in
      H(2)O(2)-treated DJ-1(-/-) cells and were decreased in wild-type DJ-1- but not
      C106S DJ-1-transfected H1299 cells through sequestration of p53 from the DUSP1
      promoter by DJ-1. DUSP1 downregulated by oxidized DJ-1 activated extracellular
      signal-regulated kinase (ERK) and decreased apoptosis. The DUSP1 and p21
      promoters harbor nonconsensus and consensus p53 recognition sequences,
      respectively, which have low affinity and high affinity for p53. However, DJ-1
      inhibited p21 promoter activity exhibited by p53 mutants harboring low DNA
      binding affinity but not by wild-type p53. These results indicate that DJ-1
      inhibits the expression of p53 target genes and depend on p53 DNA-binding
      affinity and oxidation of DJ-1 C106.

PMID- 23149934
TI  - FOXM1 promotes allergen-induced goblet cell metaplasia and pulmonary
      inflammation.
AB  - Chronic airway disorders, including chronic obstructive pulmonary disease (COPD),
      cystic fibrosis, and asthma, are associated with persistent pulmonary
      inflammation and goblet cell metaplasia and contribute to significant morbidity
      and mortality worldwide. While the molecular pathogenesis of these disorders is
      actively studied, little is known regarding the transcriptional control of goblet
      cell differentiation and mucus hyperproduction. Herein, we demonstrated that
      pulmonary allergen sensitization induces expression of FOXM1 transcription factor
      in airway epithelial and inflammatory cells. Conditional deletion of the Foxm1
      gene from either airway epithelium or myeloid inflammatory cells decreased goblet
      cell metaplasia, reduced lung inflammation, and decreased airway resistance in
      response to house dust mite allergen (HDM). FOXM1 induced goblet cell metaplasia
      and Muc5AC expression through the transcriptional activation of Spdef. FOXM1
      deletion reduced expression of CCL11, CCL24, and the chemokine receptors CCR2 and
      CX3CR1, resulting in decreased recruitment of eosinophils and macrophages to the
      lung. Deletion of FOXM1 from dendritic cells impaired the uptake of HDM antigens
      and decreased cell surface expression of major histocompatibility complex II (MHC
      II) and costimulatory molecule CD86, decreasing production of Th2 cytokines by
      activated T cells. Finally, pharmacological inhibition of FOXM1 by ARF peptide
      prevented HDM-mediated pulmonary responses. FOXM1 regulates genes critical for
      allergen-induced lung inflammation and goblet cell metaplasia.

PMID- 23149935
TI  - The SnAC domain of SWI/SNF is a histone anchor required for remodeling.
AB  - The SWI/SNF chromatin remodeling complex changes the positions where nucleosomes
      are bound to DNA, exchanges out histone dimers, and disassembles nucleosomes. All
      of these activities depend on ATP hydrolysis by the catalytic subunit Snf2,
      containing a DNA-dependent ATPase domain. Here we examine the role of another
      domain in Snf2 called SnAC (Snf2 ATP coupling) that was shown previously to
      regulate the ATPase activity of SWI/SNF. We have found that SnAC has another
      function besides regulation of ATPase activity that is even more critical for
      nucleosome remodeling by SWI/SNF. We have found that deletion of the SnAC domain
      strongly uncouples ATP hydrolysis from nucleosome movement. Deletion of SnAC does
      not adversely affect the rate, processivity, or pulling force of SWI/SNF to
      translocate along free DNA in an ATP-dependent manner. The uncoupling of ATP
      hydrolysis from nucleosome movement is shown to be due to loss of SnAC binding to
      the histone surface of nucleosomes. While the SnAC domain targets both the ATPase
      domain and histones, the SnAC domain as a histone anchor plays a more critical
      role in remodeling because it is required to convert DNA translocation into
      nucleosome movement.

PMID- 23149936
TI  - Rad51 paralog complexes BCDX2 and CX3 act at different stages in the BRCA1-BRCA2
      dependent homologous recombination pathway.
AB  - The Rad51 paralogs are required for homologous recombination (HR) and the
      maintenance of genomic stability. The molecular mechanisms by which the five
      vertebrate Rad51 paralogs regulate HR and genomic integrity remain unclear. The
      Rad51 paralogs associate with one another in two distinct complexes: Rad51B
      Rad51C-Rad51D-XRCC2 (BCDX2) and Rad51C-XRCC3 (CX3). We find that the BCDX2 and
      CX3 complexes act at different stages of the HR pathway. In response to DNA
      damage, the BCDX2 complex acts downstream of BRCA2 recruitment but upstream of
      Rad51 recruitment. In contrast, the CX3 complex acts downstream of Rad51
      recruitment but still has a marked impact on the measured frequency of homologous
      recombination. Both complexes are epistatic with BRCA2 and synthetically lethal
      with Rad52. We conclude that human Rad51 paralogs facilitate BRCA2-Rad51
      dependent homologous recombination at different stages in the pathway and
      function independently of Rad52.

PMID- 23149937
TI  - RBFOX2 is an important regulator of mesenchymal tissue-specific splicing in both
      normal and cancer tissues.
AB  - Alternative splicing provides a critical and flexible layer of regulation
      intervening in many biological processes to regulate the diversity of proteins
      and impact cell phenotype. To identify alternative splicing differences that
      distinguish epithelial from mesenchymal tissues, we have investigated hundreds of
      cassette exons using a high-throughput reverse transcription-PCR (RT-PCR)
      platform. Extensive changes in splicing were noted between epithelial and
      mesenchymal tissues in both human colon and ovarian tissues, with many changes
      from mostly one splice variant to predominantly the other. Remarkably, many of
      the splicing differences that distinguish normal mesenchymal from normal
      epithelial tissues matched those that differentiate normal ovarian tissues from
      ovarian cancer. Furthermore, because splicing profiling could classify cancer
      cell lines according to their epithelial/mesenchymal characteristics, we used
      these cancer cell lines to identify regulators for these specific splicing
      signatures. By knocking down 78 potential splicing factors in five cell lines, we
      provide an extensive view of the complex regulatory landscape associated with the
      epithelial and mesenchymal states, thus revealing that RBFOX2 is an important
      driver of mesenchymal tissue-specific splicing.

PMID- 23149938
TI  - A quantitative signaling screen identifies CARD11 mutations in the CARD and LATCH
      domains that induce Bcl10 ubiquitination and human lymphoma cell survival.
AB  - Antigen receptor signaling to NF-kappaB, essential for normal lymphocyte
      activation, is dysregulated in several types of lymphoma. During normal
      signaling, the multidomain adapter CARD11 transitions from a closed, inactive
      state to an open, active scaffold that assembles a multiprotein complex, leading
      to NF-kappaB activation. The regulation of CARD11 scaffold function is bypassed
      by lymphoma-associated oncogenic CARD11 mutations that induce spontaneous
      signaling. We report an unbiased high-throughput quantitative signaling screen
      that identifies new CARD11 hyperactive variants and defines a LATCH domain that
      functions with the CARD to promote CARD11 autoinhibition. Gain-of-function
      mutations in the LATCH or CARD disrupt inhibitory domain binding, promote Bcl10
      association, and induce Bcl10 ubiquitination, NF-kappaB activation, and human
      lymphoma cell survival. Our results identify CARD11 mutations with oncogenic
      potential, provide a mechanistic explanation for their signaling potency, and
      offer a straightforward method for the discovery of variants that promote the
      tumorigenesis of NF-kappaB-dependent lymphomas.

PMID- 23149939
TI  - A specific set of exon junction complex subunits is required for the nuclear
      retention of unspliced RNAs in Caenorhabditis elegans.
AB  - The exon junction complex (EJC) is highly conserved in many organisms and is
      involved in various steps of mRNA metabolism. During the course of investigating
      the role of EJC in the germ line sex determination of the nematode Caenorhabditis
      elegans, we found that depletion of one of the three core subunits (Y14, MAG-1,
      and eukaryotic translation initiation factor 4III [eIF4AIII]) or one auxiliary
      subunit (UAP56) of EJC resulted in the cytoplasmic leakage of unspliced RNAs from
      almost all of the C. elegans protein-coding genes examined thus far. This leakage
      was also observed with the depletion of several splicing factors, including SF3b,
      IBP160, and PRP19, all of which genetically interacted with Y14. We also found
      that Y14 physically interacts with both pre-mRNA and spliceosomal U snRNAs,
      especially U2 snRNA, and that the interaction was abolished when both IBP160 and
      PRP19 were depleted. Our results strongly suggest that a specific set of EJC
      subunits is recruited onto introns and interacts with components of the
      spliceosome, including U2 snRNP, to provide a critical signal for the
      surveillance and nuclear retention of unspliced RNAs in C. elegans.

PMID- 23149940
TI  - Blt1 and Mid1 provide overlapping membrane anchors to position the division plane
      in fission yeast.
AB  - Spatial control of cytokinesis is essential for proper cell division. The
      molecular mechanisms that anchor the dynamic assembly and constriction of the
      cytokinetic ring at the plasma membrane remain unclear. In the fission yeast
      Schizosaccharomyces pombe, the cytokinetic ring is assembled in the cell middle
      from cortical node precursors that are positioned by the anillin-like protein
      Mid1. During mitotic entry, cortical nodes mature and then compact into a
      contractile ring positioned in the cell middle. The molecular link between Mid1
      and medial cortical nodes remains poorly defined. Here we show that Blt1, a
      previously enigmatic cortical node protein, promotes the robust association of
      Mid1 with cortical nodes. Blt1 interacts with Mid1 through the RhoGEF Gef2 to
      stabilize nodes at the cell cortex during the early stages of contractile ring
      assembly. The Blt1 N terminus is required for localization and function, while
      the Blt1 C terminus promotes cortical localization by interacting with
      phospholipids. In cells lacking membrane binding by both Mid1 and Blt1, nodes
      detach from the cell cortex and generate aberrant cytokinetic rings. We conclude
      that Blt1 acts as a scaffolding protein for precursors of the cytokinetic ring
      and that Blt1 and Mid1 provide overlapping membrane anchors for proper division
      plane positioning.

PMID- 23149941
TI  - Novel checkpoint pathway organization promotes genome stability in stationary
      phase yeast cells.
AB  - Most DNA alterations occur during DNA replication in the S phase of the cell
      cycle. However, the majority of eukaryotic cells exist in a nondividing,
      quiescent state. Little is known about the factors involved in preventing DNA
      instability within this stationary-phase cell population. Previously, we utilized
      a unique assay system to identify mutations that increased minisatellite
      alterations specifically in quiescent cells in Saccharomyces cerevisiae. Here we
      conducted a modified version of synthetic genetic array analysis to determine if
      checkpoint signaling components play a role in stabilizing minisatellites in
      stationary-phase yeast cells. Our results revealed that a subset of checkpoint
      components, specifically MRC1, CSM3, TOF1, DDC1, RAD17, MEC3, TEL1, MEC1, and
      RAD53, prevent stationary-phase minisatellite alterations within the quiescent
      cell subpopulation of stationary-phase cells. Pathway analysis revealed at least
      three pathways, with MRC1, CSM3, and TOF1 acting in a pathway independent of MEC1
      and RAD53. Overall, our data indicate that some well-characterized checkpoint
      components maintain minisatellite stability in stationary-phase cells but are
      regulated differently in those cells than in actively growing cells. For the MRC1
      dependent pathway, the checkpoint itself may not be the important element;
      rather, it may be loss of the checkpoint proteins' other functions that
      contributes to DNA instability.

PMID- 23149943
TI  - A-kinase-anchoring protein-Lbc connects stress signaling to cardiac hypertrophy.

PMID- 23149942
TI  - A novel function of adipocytes in lipid antigen presentation to iNKT cells.
AB  - Systemic low-grade chronic inflammation has been intensively investigated in
      obese subjects. Recently, various immune cell types, such as macrophages,
      granulocytes, helper T cells, cytotoxic T cells, and B cells, have been
      implicated in the pathogenesis of adipose tissue inflammation. However, the roles
      of invariant natural killer T cells (iNKT cells) and the regulation of iNKT cell
      activity in adipose tissue are not thoroughly understood. Here, we demonstrated
      that iNKT cells were decreased in number in the adipose tissue of obese subjects.
      Interestingly, CD1d, a molecule involved in lipid antigen presentation to iNKT
      cells, was highly expressed in adipocytes, and CD1d-expressing adipocytes
      stimulated iNKT cell activity through physical interaction. iNKT cell population
      and CD1d expression were reduced in the adipose tissue of obese mice and humans
      compared to those of lean subjects. Moreover, iNKT cell-deficient Jalpha18
      knockout mice became more obese and exhibited increased adipose tissue
      inflammation at the early stage of obesity. These data suggest that adipocytes
      regulate iNKT cell activity via CD1d and that the interaction between adipocytes
      and iNKT cells may modulate adipose tissue inflammation in obesity.

PMID- 23149944
TI  - Altered binding site selection of p53 transcription cassettes by hepatitis B
      virus X protein.
AB  - The key cellular regulator p53 is a common target of viral oncoproteins. However,
      the mechanism by which p53 transcription regulation is modulated by hepatitis B
      virus X protein (HBx), a transcription cofactor implicated in hepatitis B virus
      associated hepatocellular carcinoma (HCC), is poorly understood. By integrating
      p53 chromatin immunoprecipitation (ChIP)-on-chip and expression profiling of an
      HBx-expressing cell culture system, we report that HBx alters p53 binding site
      selectivity in the regulatory regions of genes, and this is associated with their
      aberrant expression. Using an HBx-deregulated gene, p53AIP1, as a model, we show
      that HBx aberrantly increases p53AIP1 expression by conferring p53 selectivity
      for a more conserved binding site in its regulatory region. We further
      demonstrate that HBx-deregulated increased p53AIP1 expression is relevant in HCC
      livers and define a functional role for p53AIP1 in mediating HBx-induced
      apoptosis in vitro. Significantly, we provide evidence that specific p53
      associated transcription cofactors and coregulators are differentially recruited
      in the presence of HBx, effecting a PCAF-mediated "p53 Lys320 acetylation switch"
      that results in altered binding site selection of distinct p53 transcription
      cassettes. The findings here clarify the role of HBx in modulating p53
      transcription regulation and provide a novel mechanistic insight into this
      deregulation.

PMID- 23149945
TI  - Senataxin, defective in the neurodegenerative disorder ataxia with oculomotor
      apraxia 2, lies at the interface of transcription and the DNA damage response.
AB  - The neurodegenerative disorder ataxia with oculomotor apraxia 2 (AOA-2) is caused
      by defects in senataxin, a putative RNA/DNA helicase thought to be involved in
      the termination of transcription at RNA polymerase pause sites. RNA/DNA hybrids
      (R loops) that arise during transcription pausing lead to genome instability
      unless they are resolved efficiently. We found that senataxin forms distinct
      nuclear foci in S/G(2)-phase human cells and that the number of these foci
      increases in response to impaired DNA replication or DNA damage. Senataxin
      colocalizes with 53BP1, a key DNA damage response protein, and with other factors
      involved in DNA repair. Inhibition of transcription using alpha-amanitin, or the
      dissolution of R loops by transient expression of RNase H1, leads to the loss of
      senataxin foci. These results indicate that senataxin localizes to sites of
      collision between components of the replisome and the transcription apparatus and
      that it is targeted to R loops, where it plays an important role at the interface
      of transcription and the DNA damage response.

PMID- 23149947
TI  - Ultrananocrystalline diamond tip integrated onto a heated atomic force microscope
      cantilever.
AB  - We report a wear-resistant ultrananocrystalline (UNCD) diamond tip integrated
      onto a heated atomic force microscope (AFM) cantilever and UNCD tips integrated
      into arrays of heated AFM cantilevers. The UNCD tips are batch-fabricated and
      have apex radii of approximately 10 nm and heights up to 7 MUm. The solid-state
      heater can reach temperatures above 600  degrees C and is also a resistive
      temperature sensor. The tips were shown to be wear resistant throughout 1.2 m of
      scanning on a single-crystal silicon grating at a force of 200 nN and a speed of
      10 MUm s(-1). Under the same conditions, a silicon tip was completely blunted. We
      demonstrate the use of these heated cantilevers for thermal imaging in both
      contact mode and intermittent contact mode, with a vertical imaging resolution of
      1.9 nm. The potential application to nanolithography was also demonstrated, as
      the tip wrote hundreds of polyethylene nanostructures.

PMID- 23149946
TI  - Evaluation of CHI3L-1 and CHIT-1 expression in differentiated and polarized
      macrophages.
AB  - Chitinase 3-like protein 1 (CHI3L-1) and chitotriosidase (CHIT-1) are members of
      the chitinase family. CHI3L-1 is a newly recognized protein that is secreted by
      activated macrophages and neutrophils and expressed in a broad spectrum of
      inflammatory conditions and cancers. In human plasma, CHIT-1 activity has been
      proposed as a biochemical marker of macrophage activation. Although CHI3L-1
      expression in inflammation is under examination, little is known regarding its
      regulation during macrophages' full maturation and polarization. In this study,
      we compared CHI3L-1 and CHIT-1 modulation during monocyte to macrophage
      transition and polarization. Gene expression analysis was investigated by real
      time PCR. We found that during the maturation of monocytes into macrophages, the
      expression of both CHI3L-1 and CHIT-1 increased exponentially over time.
      Additionally, we observed a different regulation of CHI3L-1 and CHIT-1 in
      undifferentiated monocytes under stimulation with lipopolysaccharide, interferon
      gamma, and interleukin-4, at the same concentration used to polarize macrophages.
      Our finding suggests that in the immune response, the role of CHI3L-1 and CHIT-1
      is not restricted to innate immunity, but they are also protagonists in acquired
      immunity.

PMID- 23149948
TI  - Statement on matching language to the type of evidence used in describing
      outcomes data.
AB  - All scientific manuscripts should be written and edited not only for scientific
      accuracy but also for appropriateness of language used in describing the level of
      evidence. Therefore, the editors of the HEART Group (representing the world's
      cardiovascular journals) recommend that all investigators and editors carefully
      select language to 'match' the type of study conducted.

PMID- 23149949
TI  - The NHJ 2012 in retrospect: which articles are cited most?

PMID- 23149950
TI  - Source apportionment of aerosol particles near a steel plant by electron
      microscopy.
AB  - The size, morphology and chemical composition of 37,715 individual particles
      collected over 22 sampling days in the vicinity of a large integrated steel
      production were studied by scanning and transmission electron microscopy. Based
      on the morphology, chemistry and beam stability the particles were classified
      into the following fourteen groups: silicates, sea salt, calcium sulfates,
      calcium carbonates, carbonate-silicate mixtures, sulfate-silicate mixtures, iron
      oxides, iron mixtures, metal oxide-metals, complex secondary particles, soot, Cl
      rich particles, P-rich particles, and other particles. The majority of iron oxide
      (~85%) and metal oxide-metal (~70%) particles as well as ~20% of the silicate
      particles are fly ashes from high temperature processes. The emissions from the
      steel work are dominated by iron oxide particles. For source apportionment, seven
      source categories and two sectors of local wind direction (industrial and urban
      background) were distinguished. In both sectors PM10 consists of four major
      source categories: 35% secondary, 20% industrial, 17% soil and 16% soot in the
      urban background sector compared to 45% industrial, 20% secondary, 13% soil, and
      9% soot in the industrial sector. As the secondary and the soot components are
      higher in the urban background sector than in the industrial sector, it is
      concluded that both components predominantly originate from urban background
      sources (traffic, coal burning, and domestic heating). Abatement measures should
      not only focus on the steel work but should also include the urban background
      aerosol.

PMID- 23149951
TI  - Axial spondylectomy and circumferential reconstruction via a posterior approach.
AB  - BACKGROUND: Spinal metastases of the second cervical vertebra are a subset of
      tumors that are particularly difficult to address surgically. Previously
      described techniques require highly morbid circumferential dissection posterior
      to the pharynx for resection and reconstruction. OBJECTIVE: To perform a
      biomechanical analysis of instrumented reconstruction configurations used after
      axial spondylectomy and to demonstrate safe use of a novel construct in a patient
      case report. METHODS: Several different published and novel reconstruction
      configurations were inserted into 7 occipitocervical spines that underwent axial
      spondylectomy. A biomechanical analysis of the stiffness of the constructs in
      flexion and extension, lateral bending, and rotation was performed. A patient
      then underwent a posterior-only approach for axial spondylectomy and
      circumferential reconstruction. RESULTS: Biomechanical analysis of different
      constructs demonstrated that anterior column reconstruction with bilateral cages
      spanning the C1 lateral mass to the C3 facet in combination with occipitocervical
      instrumentation was superior in flexion-extension and equivalent in lateral
      bending and rotation to currently used constructs. The patient in whom this
      construct was placed via a posterior-only approach for axial spondylectomy and
      instrumentation remained at neurological baseline and demonstrated no recurrence
      of local disease or failure of instrumentation to date. CONCLUSION: When C1
      lateral mass to C3 facet bilateral cage plus occipitocervical instrumentation is
      compared with existing anterior and posterior constructs, this novel
      reconstruction is biomechanically equivalent if not superior in performance. In a
      patient, the posterior-only approach for C2 spondylectomy with the novel
      reconstruction was safe and durable and avoided the morbidity of the anterior
      approach.

PMID- 23149952
TI  - Combined "hybrid" open and minimally invasive surgical correction of adult
      thoracolumbar scoliosis:  a retrospective cohort study.
AB  - BACKGROUND: Surgery for scoliosis requires extensive exposure, resulting in
      significant tissue injury and longer recovery times. To minimize morbidity in
      scoliosis surgery, several studies have shown successful application of a
      combination of minimally invasive techniques; however, the extent of scoliosis
      treated has been modest. OBJECTIVE: To achieve some of the benefits of minimally
      invasive surgery and yet treat curves of greater degree, we have used a combined
      approach, incorporating both open and minimally invasive techniques. METHODS: We
      analyzed a prospectively acquired database in addition to reviewing electronic
      records of patients undergoing hybrid surgery for thoracolumbar scoliosis. Nine
      patients were identified. The minimally invasive portion involved the lumbar
      region in all cases. Pain was assessed by the visual analog scale and disability
      was measured by the Oswestry Disability Index. RESULTS: Mean preoperative
      scoliosis was 47.8 degrees, which was corrected to a mean 15.2 degrees. An
      average of 7.8 spinal levels was treated. Estimated blood loss averaged 1094.4
      mL, and length of hospital stay averaged 7.2 days. Acute complications occurred
      in 2 patients. Longer term complications occurred in 2 patients, consisting of
      adjacent segment disease. The mean improvement in the visual analog scale score
      was 3.7 and the mean improvement on the Oswestry Disability Index was 30.5.
      Average follow-up was 29.2 months. CONCLUSION: The hybrid approach for the
      treatment of scoliosis results in acceptable radiographic and clinical outcomes.
      Complications did not appear increased compared with those expected with
      scoliosis surgery. Although decreased adjacent tissue injury was achieved with
      the minimally invasive component of the procedure, a larger comparative study is
      required to determine magnitude of this benefit.

PMID- 23149953
TI  - Intracranial hemangiopericytoma and the role of radiation therapy:  a population
      based analysis.
AB  - BACKGROUND: Intracranial hemangiopericytoma (HPC) is a rare malignancy for which
      treatment recommendations vary. OBJECTIVE: We sought to characterize outcomes of
      HPC patients treated with postoperative external beam radiotherapy (PORT).
      METHODS: A retrospective analysis was conducted using the Surveillance,
      Epidemiology and End Results (SEER) Program of the US National Cancer Institute.
      We identified patients with intracranial hemangiopericytoma who underwent surgery
      alone or PORT. RESULTS: We identified 88 patients with a diagnosis of HPC between
      1982 and 2009 treated with surgery alone or PORT. The majority of patients were
      female (53%) and white (84%) with a median age of 50.5 years (range, 0-92 years).
      Gross total resection (GTR) was achieved in 55%, and PORT was delivered to 48% of
      the entire cohort. The median overall survival (OS) and cause-specific survival
      (CSS) were 111 months and 161 months, respectively. On univariate analysis, age
      older than 50 years correlated with poor OS (hazard ratio [HR]: 3.43; 95%
      confidence interval [CI]: 1.70-6.95; P = .001) and CSS (HR: 2.77; 95% CI: 1.18
      6.48; P = .019). On multivariate analysis (MVA), age >50 years correlated with
      poor OS (HR: 3.69; 95% CI: 1.72-7.93; P = .001) and CSS (HR: 2.67; 95% CI: 1.08
      6.59; P = .034). On MVA, GTR correlated with improved OS (HR: 0.28; 95% CI: 0.11
      0.71; P = .007) and CSS (HR: 0.23; 95% CI: 0.07-0.76; P = .016). In addition,
      PORT correlated with improved OS (MVA HR: 0.02; 95% CI: 0.00-0.31; P = .005) and
      CSS (MVA HR: 0.02; 95% CI: 0.00-0.45; P = .015). Patients undergoing STR with
      PORT compared favorably with those undergoing GTR alone with respect to OS (HR:
      0.43; 95% CI: 0.15-1.26; P = .13) and CSS (HR: 0.51; 95% CI: 0.15-1.78; P = .29).
      CONCLUSION: In intracranial HPC, both PORT and GTR independently correlate with
      improved OS and CSS.

PMID- 23149954
TI  - Everything to gain: Sir Hugh Cairns' treatment of central nervous system
      infection at Oxford and abroad.
AB  - Antibiotics have revolutionized survival from central nervous system (CNS)
      infections. Sixty years after the death of Sir Hugh Cairns, we present archive
      material of historical interest from the Radcliffe Infirmary in Oxford from the
      time of his first trials of penicillin for CNS infection. We discuss Cairns'
      important wartime and subsequent contributions to antibiosis in CNS infection and
      include drawings by Audrey Arnott illustrating the surgical techniques used to
      treat abscesses at the time.

PMID- 23149955
TI  - Familial intracranial dural arteriovenous fistulas.
AB  - BACKGROUND AND IMPORTANCE: Intracranial dural arteriovenous fistulas (DAVFs) are
      acquired abnormal communications between dural arteries and veins. Risk factors
      for development include sinus thrombosis and hypercoagulability, such as occurs
      in heritable thrombophilias. While there have been reports of other types of
      vascular anomalies (such as cavernous and arteriovenous malformations) occurring
      in families, to our knowledge there have been no reports of familial intracranial
      DAVFs. We describe the first 2 cases of intracranial DAVFs occurring in first
      degree relatives. CLINICAL PRESENTATION: A 66-year-old woman presented with an 18
      month history of bilateral pulsatile tinnitus. Neurological examination was
      significant for a prominent pulsatile bruit over the left mastoid region.
      Laboratory studies demonstrated heterozygosity for Prothrombin G20210A mutation.
      Imaging disclosed a large left Type I Borden DAVF involving the distal transverse
      sigmoid sinus junction. She underwent uncomplicated stereotactic radiosurgery to
      the fistula that led to complete resolution of her tinnitus and the fistula. A 73
      year-old woman, the sister of the previous patient, presented with a 24-month
      history of pulsatile tinnitus affecting the left ear. Laboratory studies
      demonstrated heterozygosity for the Prothrombin G20210A mutation. Imaging
      revealed a left Type I Borden DAVF involving the left transverse and sigmoid
      sinuses. The patient's symptoms resolved spontaneously without treatment. Repeat
      imaging revealed interval involution of the fistula. CONCLUSION: We describe 2
      sisters who were heterozygous for Prothrombin G20210A mutation and found to have
      DAVFs. Clinicians should be aware of the potential for these fistulas to
      congregate in first-degree relatives via heritable thrombophilias such as the
      Prothrombin G20210A mutation.

PMID- 23149956
TI  - Effect of severity of rod contour on posterior rod failure in the setting of
      lumbar pedicle subtraction osteotomy (PSO): a biomechanical study.
AB  - BACKGROUND: Rod failure has been reported clinically in pedicle subtraction
      osteotomy (PSO) to correct flat back deformity. OBJECTIVE: To characterize the
      fatigue life of posterior screw-rod constructs in the setting of PSO as a
      function of the severity of rod contour angle. METHODS: A modified ASTM F1717 to
      04 was used. Rods were contoured to the appropriate angle for the equivalent 20-,
      40-, or 60-degree PSO angles. Testing was performed on a mechanical test frame at
      400/40 N and 250/25 N, and specimens were cycled at 4 Hz to failure or run-out at
      2,000,000 cycles. The effect of the screw-rod system on fatigue strength of
      curved rods was compared using Cox proportional hazards regression. RESULTS: At
      400 N/40 N, Cox proportional hazards regression indicated that contouring rods
      from a 20-degree PSO angle to either 40 or 60 degrees significantly decreased
      fatigue life (hazard ratio = 7863.6, P = .0144). However, contouring rods from a
      40-degree PSO angle to 60 degrees had no significant effect on the fatigue life
      (P > .05). At 250 N/25 N, Cox proportional hazards regression indicated that
      contouring rods from a 20-degree PSO angle to either 40 or 60 degrees
      significantly decreased fatigue life (hazard ratio = 7863.6, P = .0144).
      Furthermore, contouring rods from a 40-degree PSO angle to 60 degrees had a
      significant effect on the fatigue life (hazard ratio = 7863.6, P = .0144).
      CONCLUSION: Results suggest that in the setting of PSO, the fatigue life of
      posterior spinal fixation rods depends largely on the severity of the rod angle
      used to maintain the vertebral angle created by the PSO and is significantly
      lowered by rod contouring.

PMID- 23149957
TI  - Direct lateral approach to pathology at the craniocervical junction.

PMID- 23149958
TI  - Thoracolumbar spinal extradural arachnoid cysts.

PMID- 23149959
TI  - In reply. Direct lateral approach to pathology at the craniocervical junction.

PMID- 23149960
TI  - Transcranial Doppler derived pulsatility index in the assessment of intracranial
      pressure:  the trend is your friend.

PMID- 23149961
TI  - The genetics of moyamoya disease:  recent insights into the pathogenesis of the
      disease.

PMID- 23149962
TI  - In reply. The genetics of moyamoya disease: recent insights into the pathogenesis
      of the disease.

PMID- 23149963
TI  - 5-aminolevulinic acid fluorescence-guided resection of intramedullary ependymoma:
      report of 9 cases.
AB  - BACKGROUND: Resection guided by 5-aminolevulinic acid (5-ALA) fluorescence has
      proved to be useful in intracranial glioma surgery. However, the effects of 5-ALA
      on spinal cord tumors remain unknown. OBJECTIVE: To evaluate the usefulness of 5
      ALA fluorescence-guided resection of intramedullary ependymoma for achieving
      maximum tumor resection. METHODS: This study included 10 patients who underwent
      surgical resection of an intramedullary ependymoma. Nine patients were orally
      administered 5-ALA (20 mg/kg) 2 hours before the induction of anesthesia. 5-ALA
      fluorescence was visualized with an operating microscope. Tumors were removed in
      a standardized manner with electrophysiological monitoring. The extent of
      resection was evaluated on the basis of intraoperative findings and postoperative
      magnetic resonance imaging. Histopathological diagnosis was established according
      to World Health Organization 2007 criteria. Cell proliferation was assessed by Ki
      67 labeling index. RESULTS: 5-ALA fluorescence was positive in 7 patients (6
      grade II and 1 grade III) and negative in 2 patients (grade II). Intraoperative
      findings were dichotomized: Tumors covered by the cyst were easily separated from
      the normal parenchyma, whereas tumors without the cyst appeared to be continuous
      to the spinal cord. In these cases, 5-ALA fluorescence was especially valuable in
      delineating the ventral and cranial and caudal margins. Ki-67 labeling index was
      significantly higher in 5-ALA-positive cases compared with 5-ALA-negative cases.
      All patients improved neurologically or stabilized after surgery. CONCLUSION: 5
      ALA fluorescence was useful for detecting tumor margins during surgery for
      intramedullary ependymoma. When combined with electrophysiological monitoring,
      fluorescence-guided resection could help to achieve maximum tumor resection
      safely.

PMID- 23149964
TI  - Simplified azygos anterior cerebral bypass: y-shaped superficial temporal artery
      interposition graft from A2 with double reimplantation of pericallosal arteries:
      technical case report.
AB  - BACKGROUND AND IMPORTANCE: Trapping with distal revascularization is a
      therapeutic option for giant aneurysms that cannot be clipped or coiled. In skull
      base lesions such as meningiomas, arterial encasement is often present,
      requiring, in some cases, revascularization procedures: extracranial-to
      intracranial bypass and more recently intracranial-to-intracranial techniques.
      These techniques are used only in exceptional cases of tumors in other
      localizations. CLINICAL PRESENTATION: We report a case of a recurrent malignant
      frontal falx meningioma with encasement of both pericallosal arteries (PcaAs).
      During resection of the lesion, the left PcaA was sectioned and the right PcaA
      was occluded for manipulation and coagulation of the tumor. The occlusion was
      diagnosed with indocyanine green videoangiography. A Y-shaped superficial
      temporal artery graft was obtained in the right side, and the anterior cerebral
      artery circulation was reconstructed using an intracranial-to-intracranial bypass
      in the following fashion: right A2 to superficial temporal artery Y-shaped graft
      for both PcaAs. The patient's postoperative period was uneventful with no
      deficit, and the computed tomography angiography showed the preservation of both
      PcaAs. CONCLUSION: To the best of our knowledge, this microsurgical
      reconstruction of the PcaAs has not been performed before in a meningioma or a
      complex aneurysm case. We think the use of a superficial temporal artery as an in
      situ graft is more straightforward compared with other interposition grafts such
      as the radial artery graft or saphenous vein graft. The use of intracranial-to
      intracranial techniques is the proper evolution of the use of classic
      extracranial-to-intracranial cerebral revascularization techniques.

PMID- 23149965
TI  - Intraoperative monitoring of an aspect of executive functions: administration of
      the Stroop test in 9 adult patients during awake surgery for resection of frontal
      glioma.
AB  - BACKGROUND: Awake brain surgery allows extensive intraoperative monitoring of not
      only motor and sensory functions and language but also executive functions.
      OBJECTIVE: To administer the Stroop test intraoperatively to avoid dramatic side
      effects such as akinetic mutism and to monitor executive functions in an attempt
      to optimize the benefit/risk balance of surgery. METHODS: A series of 9 adult
      patients with frontal glioma were operated on for gross tumor resection under
      local anesthesia. All procedures involved the anterior cingulate cortex (ACC).
      RESULTS: Three types of response to the Stroop test were observed: 3 patients had
      a Stroop effect only for stimulation of the contralateral ACC; 3 patients had a
      Stroop effect for stimulation of the ipsilateral ACC; and 3 patients had no
      Stroop effect. Preoperative and postoperative neuropsychological and surgical
      results are presented and discussed. Stimulation sites eliciting a Stroop effect
      are compared with published image-based data, and insight provided by these
      surgical data regarding ACC function and plasticity is discussed. No operative
      complication related to intraoperative administration of the Stroop test was
      observed. CONCLUSION: Administration of the Stroop test during resection of
      gliomas involving the ACC in adult patients is an option for intraoperative
      monitoring of executive functions during awake surgery. Globally, these results
      suggest functional compensation, mediated by plasticity mechanisms, by
      contralateral homologous regions of the ACC in adult patients with frontal
      glioma.

PMID- 23149966
TI  - Prevalence and characteristics of concurrent down syndrome in patients with
      moyamoya disease.
AB  - BACKGROUND: An association between moyamoya disease and Down syndrome appears to
      exist on the basis of reported anecdotal cases in the literature. OBJECTIVE: To
      determine the prevalence of Down syndrome associated with moyamoya disease in
      inpatients and to identify the demographic and clinical features of moyamoya
      disease that may be unique when associated with Down syndrome. METHODS: In this
      observational study, we analyzed data from the Nationwide Inpatient Sample
      between 2002 and 2009 using International Classification of Diseases codes for
      moyamoya disease and Down syndrome for patient identification. Data including
      patient age, sex, race/ethnicity, secondary diagnosis, procedures, hospital
      costs, and patient outcomes were obtained. RESULTS: From 2002 to 2009, an
      estimated 518 patients (mean +/- SD age, 16.2 +/- 1.68 years) with coexisting
      moyamoya disease and Down syndrome were admitted. The estimated prevalence was
      3.8% (3760 per 100,000) among patients admitted with moyamoya disease and 9.5%
      (9540 per 100,000) among moyamoya patients < 15 years of age. Patients admitted
      with moyamoya disease and Down syndrome were most frequently white and Hispanic
      (P = .02). They were more likely to present with ischemic stroke and less
      commonly with hemorrhagic stroke (15.3% and 2.7%, respectively; P < .05).
      CONCLUSION: This is the first study to estimate the prevalence of Down syndrome
      in patients with moyamoya disease. The 26-fold-greater prevalence of Down
      syndrome in patients with coexisting moyamoya disease compared with the
      prevalence of Down syndrome among live births (145 per 100,000) highlights the
      need for a better understanding of the common pathophysiology of the 2
      conditions.

PMID- 23149967
TI  - Cranioplasty with custom-made titanium plates--14 years experience.
AB  - BACKGROUND: There is no consensus on which material is best suited for repair of
      cranial defects. OBJECTIVE: To investigate the outcomes following custom-made
      titanium cranioplasty. METHODS: The medical records for all patients who had
      titanium cranioplasty at 2 major neurosurgical centers in Western Australia were
      retrieved and analyzed for this retrospective cohort study. RESULTS: Altogether,
      127 custom-made titanium cranioplasties on 113 patients were included. Two
      patients had 3 titanium cranioplasties and 10 patients had 2. Infected bone flap
      (n = 61, 54%), either from previous craniotomy or autologous cranioplasty, and
      contaminated bone flap (n = 16, 14%) from the initial injury were the main
      reasons for requiring titanium cranioplasty. Complications attributed to titanium
      cranioplasty were common (n = 33, 29%), with infection being the most frequent
      complication (n = 18 patients, 16%). Complications were, on average, associated
      with an extra 7 days of hospital stay (interquartile range 2-17). The use of
      titanium as the material for the initial cranioplasty (P = .58), the presence of
      skull fracture(s) (P > .99) or scalp laceration(s) (P = .32) at the original
      surgery, and proven local infection before titanium cranioplasty (P = .78) were
      not significantly associated with an increased risk of infection. Infection was
      significantly more common after titanium cranioplasty for large defects
      (hemicraniectomy [39%] and bifrontal craniectomy [28%]) than after cranioplasty
      for small defects (P = .04). CONCLUSION: Complications after using titanium plate
      for primary or secondary cranioplasty were common (29%) and associated with an
      increased length of hospital stay. Infection was a major complication (16%), and
      this suggested that more vigorous perioperative infection prophylaxis is needed
      for titanium plate cranioplasty.

PMID- 23149968
TI  - Culture of olfactory ensheathing cells for central nerve repair:  the limitations
      and potential of endoscopic olfactory mucosal biopsy.
AB  - BACKGROUND: Autotransplantation of olfactory ensheathing cells (OECs) into the
      damaged central nervous system is a potential therapeutic strategy for spinal
      cord and root cord injuries. One limiting factor has been the poor OEC yields
      from human mucosal biopsies. Previous studies have only commented on their
      success in obtaining mucosal specimens containing olfactory mucosa, but have not
      commented on the yield of OECs from those specimens. OBJECTIVE: To describe a
      reproducible and safe surgical technique for obtaining human olfactory mucosa and
      identify patient factors that possibly affect the yield of OEC cultures from the
      human olfactory mucosa. METHODS: We obtained mucosal biopsies from 43 consecutive
      patients by using a novel reproducible surgical technique and our laboratory
      culture protocol. The Spearman rank correlation coefficient was used to assess
      the relationship between OECs and fibroblast yield with patient characteristics
      and specimen factors. RESULTS: A greater yield of OECs was obtained from patients
      of younger age. In addition, patients with worse mucosal disease yielded poorer
      cell cultures. Greatest yields were found in patients with absence of mucosal
      disease. Furthermore, a higher yield of OECs was obtained from specimens
      harvested from the more caudal portions of the superior turbinate, and OEC yield
      did not correlate with the ventroposterior location of the biopsy. CONCLUSION: We
      have provided evidence that biopsies closer to the cribriform plate can produce
      larger yields of OECs, and that patient factors like age and mucosal disease
      adversely affect the culture yield.

PMID- 23149969
TI  - Cavity volume dynamics after resection of brain metastases and timing of
      postresection cavity stereotactic radiosurgery.
AB  - BACKGROUND: An alternative treatment option to whole-brain irradiation after
      surgical resection of brain metastases is resection cavity stereotactic
      radiosurgery (SRS). OBJECTIVE: To review the dynamics of cavity volume change
      after surgical resection with the goal of determining the optimal timing for
      cavity SRS. METHODS: Preresection tumor, postresection/pre-SRS cavity, and post
      SRS cavity volumes were measured for 68 cavities in 63 patients treated with
      surgery and postresection cavity SRS. Percent differences between volumes were
      calculated and correlation analyses were performed to assess volume changes
      before and after SRS. RESULTS: For the majority of tumors, the postresection
      cavity volume was smaller than the preresection tumor volume by a median percent
      volume change of -29% (range, -82% to 1258%), with larger preresection tumors
      resulting in greater cavity shrinkage (P < .001). To determine the optimal timing
      for cavity SRS, we examined cavity volume dynamics by comparing the early
      postresection (postoperative days 0-3) and treatment planning magnetic resonance
      imaging scans (median time to magnetic resonance imaging, 20 days; range, 9-33
      days) and found no association between the postresection day number and volume
      change (P = .75). The volume decrease resulting from tumor resection was offset
      by the addition of a 2-mm clinical target volume margin, which is our current
      technique. CONCLUSION: The greatest volume change occurs immediately after
      surgery (postoperative days 0-3) with no statistically significant volume change
      occurring up to 33 days after surgery for most patients. Therefore, there is no
      benefit of cavity shrinkage in waiting longer than the first 1 to 2 weeks to
      perform cavity SRS.

PMID- 23149970
TI  - Feasibility, safety, and periprocedural complications associated with
      endovascular treatment of selected ruptured aneurysms under conscious sedation
      and local anesthesia.
AB  - BACKGROUND: Endovascular coil embolization of ruptured aneurysms is performed
      under general anesthesia at most centers for perceived improved image quality and
      patient safety. OBJECTIVE: To report the feasibility of and outcomes associated
      with endovascular treatment of subarachnoid hemorrhage (SAH) patients with
      ruptured cerebral aneurysms performed under conscious sedation with local
      anesthetics. METHODS: Between January 2005 and December 2009, 187 patients with
      aneurysmal SAH were treated with coil embolization at the authors' hospital. For
      each patient, procedural details, mode of anesthesia, and clinical and
      radiographic outcomes were reviewed retrospectively (retrospective case series).
      RESULTS: A total of 197 coil embolizations were performed: 112 under general
      anesthesia, 78 under conscious sedation with local anesthetics, and 7 converted
      from conscious sedation to general anesthesia. None of the patients who presented
      with Hunt & Hess grade IV or V were treated under conscious sedation. For
      patients who presented with Hunt & Hess grades I, II, and III, 79.2%, 66.7%, and
      32.6% of patients, respectively, underwent successful completion of treatment
      under conscious sedation. The symptomatic procedural complication rate was 2.5%
      overall and 2.4% for the conscious sedation group alone. Among the 14
      interventions with intraprocedural perforation, 11 were performed under general
      anesthesia and 3 were performed under conscious sedation. CONCLUSION: In the
      authors' experience, conscious sedation with local anesthetics for endovascular
      treatment of ruptured intracranial aneurysms is feasible and safe in most
      patients with low-grade SAH. It may allow direct evaluation of the patient's
      neurological status, potentially leading to earlier detection and response to
      intraprocedural complications.

PMID- 23149971
TI  - Electroencephalographic changes following direct current deep brain stimulation
      of auditory cortex:  a new model for investigating neuromodulation.
AB  - BACKGROUND: Although deep brain (DBS) and transcranial direct current stimulation
      (tDCS) are used as investigative tools and therapies for a variety of
      neurological and psychiatric conditions, their mechanisms of action remain poorly
      understood. Therefore, there is a need for new animal models of neuromodulation.
      OBJECTIVE: To introduce and validate a direct current DBS (DC-DBS) model that
      will use the anatomic precision of intracranial electrodes, as used in DBS, to
      apply direct current, as used in tDCS, over primary auditory cortex (A1) and
      induce electroencephalographic (EEG) changes. METHODS: Twenty-four mice were
      assigned to 1 of 2 stimulation groups or a sham group and were implanted with
      electrodes in A1. Stimulation groups underwent DC-DBS stimulation for 20 minutes
      at 20 MUA. Auditory EEG was recorded before stimulation and at 1 hour, 1 week,
      and 2 weeks poststimulation. EEG was analyzed for changes in N1 (N100 in humans,
      N40 in mice) amplitude and latency as well as delta and theta power. RESULTS: DC
      DBS led to significant EEG changes (all P values < .05). Among the stimulated
      animals, there were durable reductions in delta and theta power. There were no
      differences within the sham group, and neither N40 latencies nor amplitudes
      changed across time. CONCLUSION: Our results show DC-DBS-induced reductions in
      slow-wave activity consistent with recent tDCS studies. We propose that this
      model will provide a means to explore basic mechanisms of neuromodulation and
      could facilitate future application of DC-DBS in humans.

PMID- 23149972
TI  - Results of stent-assisted vs non-stent-assisted endovascular therapies in 489
      cerebral aneurysms: single-center experience.
AB  - BACKGROUND: Whether the addition of stenting to intracranial aneurysm coil
      embolization results in benefit in terms of occlusion rates or additional risk in
      terms of periprocedural adverse events is not clear. OBJECTIVE: To report
      retrospectively analyzed results of endovascular aneurysm treatment comparing
      stent-assisted coiling with coiling without stents at our hospital from 2005 to
      2009. METHODS: In this retrospectively reviewed case series, aneurysms were
      grouped as intent-to-treat or initially treated with stent-assisted coiling (A)
      vs coiling alone (B) or as-treated-those that ultimately received a stent (C) or
      not (D). Complication and occlusion rates were compared between groups. Some
      patients crossed from group B to C after receiving stent placement at a later
      treatment following the initial therapeutic modality (without a stent). RESULTS:
      In 459 patients, 489 aneurysms were treated by group as follows: A = 181, B =
      308, C = 225, and D = 264. In stent groups (A and C), there were significantly
      lower frequencies of ruptured aneurysms (A vs B = 11% vs 62%, P < .001; C vs D =
      20.4% vs 62.5%, P < .001) and more giant aneurysms (A vs B = 7.3% vs 1.0%, P =
      .001; C vs D = 5.9% vs 1.1%, P < .001). There was no statistically significant
      difference in permanent event-related morbidity (A vs B = 4.4% vs 4.2%, P = 1.0;
      C vs D = 4.4% vs 4.2%, P = 1.0). Average angiographic follow-up after last
      treatment was 18.2 +/- 15 months (median = 14). Higher rates of complete
      occlusion at last angiographic follow-up were observed in stented aneurysms (A vs
      B = 64.6% vs 49.7%, P = .001; C vs D = 62.7% vs 48.9%, P = .003). CONCLUSION:
      Stent-assisted aneurysm treatment resulted in higher total occlusion rates than
      non-stent-assisted treatment, with acceptable, comparable periprocedural event
      rates.

PMID- 23149973
TI  - Autologous iliac bone graft with anterior plating is advantageous over the stand
      alone cage for segmental lordosis in single-level cervical disc disease.
AB  - BACKGROUND: Anterior cervical discectomy and fusion (ACDF) with autologous iliac
      bone graft and plating has been a standard surgical method for single-level
      cervical disc disease. The stand-alone cage was introduced to reduce graft
      related morbidity. However, problems due to focal kyphosis at the operated level
      have been on the rise. It has been difficult to derive a conclusive answer from
      previous studies for the indications of each method. OBJECTIVE: An interim
      analysis of a prospective randomized study was performed to compare the sagittal
      alignment between a stand-alone cage (ACDF cage) and autologous iliac bone graft
      and plating (ACDF plate). METHODS: Twenty-nine patients were allocated to the
      ACDF-cage group (M:F = 17:12) and 23 to the ACDF-plate group (M:F = 14:9). Cobb
      angles at the operated segment (segmental angle, SA; lordosis vs kyphosis) were
      compared at postoperative 12 months and the other confounding factors were
      explored. RESULTS: Demographic features were not different between groups. The
      fusion method significantly affected segmental alignment at 12 months (P = .03;
      odds ratio, 5.52). Preoperatively, the SA was not different between the groups (P
      = .18) and was similar (P = .22) immediately following the operation. However,
      the SA was significantly more lordotic (P < .05) in the ACDF-plate group at
      postoperative 12 months in comparison with the ACDF-cage group. There was no
      other significant risk factor for segmental kyphosis. CONCLUSION: The stand-alone
      cage and autologous bone graft with plating had similar clinical outcomes, but
      stand-alone cage fusion may be disadvantageous from a radiological viewpoint.

PMID- 23149974
TI  - Endoscopic transsphenoidal surgery for cushing disease:  techniques, outcomes,
      and predictors of remission.
AB  - BACKGROUND: The efficacy of endoscopic transsphenoidal surgery (ETS) for Cushing
      disease has not been clearly established. OBJECTIVE: To assess efficacy of a pure
      endoscopic approach for treatment of Cushing disease and determine predictors of
      remission. METHODS: A prospectively acquired database of 61 patients undergoing
      ETS was reviewed. Remission was defined as postoperative morning serum cortisol
      of <5 MUg/dL or normal or decreased 24-hour urine-free cortisol level in follow
      up. RESULTS: Overall, hypercortisolemia resolved in 58 of 61 patients (95%) by
      discharge. Tumor size did not predict resolution of hypercortisolemia at
      discharge (microadenomas [97%], magnetic resonance imaging-negative Cushing
      [100%], macroadenomas [87%]). At 2- to 3-month evaluations, 45 of 49 patients
      (91.8%) were in remission. Fifty patients were followed for at least 12 months
      (mean, 28 months; range, 12-72). Forty-two (84%) achieved remission from a single
      ETS. In these patients, there was no significant difference in remission rates
      between microadenomas (93%), magnetic resonance imaging-negative (70%), and
      macroadenomas (77%). Patients with history of previous surgery (n = 14, 23%) were
      9 times less likely to achieve follow-up remission (P = .021). In-house cortisol
      level of <5.7 MUg/dL provided the best prediction of follow-up remission
      (sensitivity 88.6%, specificity 83.3%). Postoperative diabetes insipidus occurred
      transiently in 7 patients (9%) and permanently in 3 (5%). One patient experienced
      postoperative cerebrospinal fluid leak that resolved with further surgery.
      CONCLUSION: ETS for Cushing disease provides high rates of remission with low
      rates of complications regardless of size. Although patients with a history of
      previous surgery are less likely to achieve remission, the majority can still
      achieve remission following treatment.

PMID- 23149975
TI  - Long-term outcomes of deep brain stimulation for neuropathic pain.
AB  - BACKGROUND: Deep brain stimulation (DBS) to treat neuropathic pain refractory to
      pharmacotherapy has reported variable outcomes and has gained United Kingdom but
      not USA regulatory approval. OBJECTIVE: To prospectively assess long-term
      efficacy of DBS for chronic neuropathic pain in a single-center case series.
      METHODS: Patient reported outcome measures were collated before and after
      surgery, using a visual analog score, short-form 36-question quality-of-life
      survey, McGill pain questionnaire, and EuroQol-5D questionnaires (EQ-5D and
      health state). RESULTS: One hundred ninety-seven patients were referred over 12
      years, of whom 85 received DBS for various etiologies: 9 amputees, 7 brachial
      plexus injuries, 31 after stroke, 13 with spinal pathology, 15 with head and face
      pain, and 10 miscellaneous. Mean age at surgery was 52 years, and mean follow-up
      was 19.6 months. Contralateral DBS targeted the periventricular gray area (n =
      33), the ventral posterior nuclei of the thalamus (n = 15), or both targets (n =
      37). Almost 70% (69.4%) of patients retained implants 6 months after surgery.
      Thirty-nine of 59 (66%) of those implanted gained benefit and efficacy varied by
      etiology, improving outcomes in 89% after amputation and 70% after stroke. In
      this cohort, >30% improvements sustained in visual analog score, McGill pain
      questionnaire, short-form 36-question quality-of-life survey, and EuroQol-5D
      questionnaire were observed in 15 patients with >42 months of follow-up, with
      several outcome measures improving from those assessed at 1 year. CONCLUSION: DBS
      for pain has long-term efficacy for select etiologies. Clinical trials retaining
      patients in long-term follow-up are desirable to confirm findings from
      prospectively assessed case series.

PMID- 23149976
TI  - Iatrogenic vascular complications associated with external ventricular drain
      placement: a report of 8 cases and review of the literature.
AB  - BACKGROUND: Placement of an external ventricular drain (EVD) is a commonly
      performed and often lifesaving procedure. Although hemorrhage is one of the
      commonest complications associated with the procedure, ventricular catheter
      induced vascular injury is rarely reported. OBJECTIVE: To describe 9 cases of EVD
      related vascular trauma: 7 arteriovenous fistulas and 2 traumatic aneurysms.
      METHODS: During a 3-year period, 299 patients had EVDs placed. Eight patients
      (2.75%), 3 male and 5 female (mean age, 48 +/- 20 years), developed vascular
      lesions associated with EVDs. Six patients developed arteriovenous fistulas and 2
      patients developed a traumatic aneurysm. The arterial feeders of 5 superficial
      draining fistulas arose from the middle meningeal artery, and the arterial feeder
      of a deep-draining fistula originated from a lenticulostriate artery. One
      traumatic aneurysm arose from a distal branch of the anterior cerebral artery,
      and the second from a branch of the superficial temporal artery. Four of the
      superficial fistulas were treated with transarterial embolization. RESULTS: Two
      superficial fistulas and the deep-draining fistula resolved spontaneously after
      EVD removal. The intracranial aneurysm was embolized with Onyx18, and the
      superficial temporal artery aneurysm was managed conservatively. There were no
      hemorrhages associated with any of these vascular lesions and no complications
      after treatment. CONCLUSION: Our data suggest that iatrogenic vascular trauma
      associated with EVD insertions (2.75%) may be more common than is currently
      appreciated. Endovascular treatment is effective and may be necessary when these
      lesions do not resolve spontaneously.

PMID- 23149977
TI  - Generation of human induced pluripotent stem cells from peripheral blood using
      the STEMCCA lentiviral vector.
AB  - Through the ectopic expression of four transcription factors, Oct4, Klf4, Sox2
      and cMyc, human somatic cells can be converted to a pluripotent state, generating
      so-called induced pluripotent stem cells (iPSCs)(1-4). Patient-specific iPSCs
      lack the ethical concerns that surround embryonic stem cells (ESCs) and would
      bypass possible immune rejection. Thus, iPSCs have attracted considerable
      attention for disease modeling studies, the screening of pharmacological
      compounds, and regenerative therapies(5). We have shown the generation of
      transgene-free human iPSCs from patients with different lung diseases using a
      single excisable polycistronic lentiviral Stem Cell Cassette (STEMCCA) encoding
      the Yamanaka factors(6). These iPSC lines were generated from skin fibroblasts,
      the most common cell type used for reprogramming. Normally, obtaining fibroblasts
      requires a skin punch biopsy followed by expansion of the cells in culture for a
      few passages. Importantly, a number of groups have reported the reprogramming of
      human peripheral blood cells into iPSCs(7-9). In one study, a Tet inducible
      version of the STEMCCA vector was employed(9), which required the blood cells to
      be simultaneously infected with a constitutively active lentivirus encoding the
      reverse tetracycline transactivator. In contrast to fibroblasts, peripheral blood
      cells can be collected via minimally invasive procedures, greatly reducing the
      discomfort and distress of the patient. A simple and effective protocol for
      reprogramming blood cells using a constitutive single excisable vector may
      accelerate the application of iPSC technology by making it accessible to a
      broader research community. Furthermore, reprogramming of peripheral blood cells
      allows for the generation of iPSCs from individuals in which skin biopsies should
      be avoided (i.e. aberrant scarring) or due to pre-existing disease conditions
      preventing access to punch biopsies. Here we demonstrate a protocol for the
      generation of human iPSCs from peripheral blood mononuclear cells (PBMCs) using a
      single floxed-excisable lentiviral vector constitutively expressing the 4
      factors. Freshly collected or thawed PBMCs are expanded for 9 days as
      described(10,11) in medium containing ascorbic acid, SCF, IGF-1, IL-3 and EPO
      before being transduced with the STEMCCA lentivirus. Cells are then plated onto
      MEFs and ESC-like colonies can be visualized two weeks after infection. Finally,
      selected clones are expanded and tested for the expression of the pluripotency
      markers SSEA-4, Tra-1-60 and Tra-1-81. This protocol is simple, robust and highly
      consistent, providing a reliable methodology for the generation of human iPSCs
      from readily accessible 4 ml of blood.

PMID- 23149979
TI  - Dietary information improves cardiovascular disease risk prediction models.
AB  - BACKGROUND/OBJECTIVES: Data are limited on cardiovascular disease (CVD) risk
      prediction models that include dietary predictors. Using known risk factors and
      dietary information, we constructed and evaluated CVD risk prediction models.
      SUBJECTS/METHODS: Data for modeling were from population-based prospective cohort
      studies comprised of 9026 men and women aged 40-69 years. At baseline, all were
      free of known CVD and cancer, and were followed up for CVD incidence during an 8
      year period. We used Cox proportional hazard regression analysis to construct a
      traditional risk factor model, an office-based model, and two diet-containing
      models and evaluated these models by calculating Akaike information criterion
      (AIC), C-statistics, integrated discrimination improvement (IDI), net
      reclassification improvement (NRI) and calibration statistic. RESULTS: We
      constructed diet-containing models with significant dietary predictors such as
      poultry, legumes, carbonated soft drinks or green tea consumption. Adding dietary
      predictors to the traditional model yielded a decrease in AIC (delta AIC=15), a
      53% increase in relative IDI (P-value for IDI <0.001) and an increase in NRI
      (category-free NRI=0.14, P <0.001). The simplified diet-containing model also
      showed a decrease in AIC (delta AIC=14), a 38% increase in relative IDI (P-value
      for IDI <0.001) and an increase in NRI (category-free NRI=0.08, P<0.01) compared
      with the office-based model. The calibration plots for risk prediction
      demonstrated that the inclusion of dietary predictors contributes to better
      agreement in persons at high risk for CVD. C-statistics for the four models were
      acceptable and comparable. CONCLUSIONS: We suggest that dietary information may
      be useful in constructing CVD risk prediction models.

PMID- 23149984
TI  - The cover: Strike on the pier.

PMID- 23149987
TI  - Treatment of substance abuse in military hampered by "old-fashioned" approach.

PMID- 23149980
TI  - Alcohol dehydrogenase and aldehyde dehydrogenase gene polymorphisms, alcohol
      intake and the risk of colorectal cancer in the European Prospective
      Investigation into Cancer and Nutrition study.
AB  - BACKGROUND/OBJECTIVES: Heavy alcohol drinking is a risk factor of colorectal
      cancer (CRC), but little is known on the effect of polymorphisms in the alcohol
      metabolizing enzymes, alcohol dehydrogenase (ADH) and aldehyde dehydrogenase
      (ALDH) on the alcohol-related risk of CRC in Caucasian populations.
      SUBJECTS/METHODS: A nested case-control study (1269 cases matched to 2107
      controls by sex, age, study centre and date of blood collection) was conducted
      within the European Prospective Investigation into Cancer and Nutrition (EPIC) to
      evaluate the impact of rs1229984 (ADH1B), rs1573496 (ADH7) and rs441 (ALDH2)
      polymorphisms on CRC risk. Using the wild-type variant of each polymorphism as
      reference category, CRC risk estimates were calculated using conditional logistic
      regression, with adjustment for matching factors. RESULTS: Individuals carrying
      one copy of the rs1229984(A) (ADH1B) allele (fast metabolizers) showed an average
      daily alcohol intake of 4.3 g per day lower than subjects with two copies of the
      rs1229984(G) allele (slow metabolizers) (P(diff)<0.01). None of the polymorphisms
      was associated with risk of CRC or cancers of the colon or rectum. Heavy alcohol
      intake was more strongly associated with CRC risk among carriers of the
      rs1573496(C) allele, with odds ratio equal to 2.13 (95% confidence interval: 1.26
      3.59) compared with wild-type subjects with low alcohol consumption
      (P(interaction)=0.07). CONCLUSIONS: The rs1229984(A) (ADH1B) allele was
      associated with a reduction in alcohol consumption. The rs1229984 (ADH1B),
      rs1573496 (ADH7) and rs441 (ALDH2) polymorphisms were not associated with CRC
      risk overall in Western-European populations. However, the relationship between
      alcohol and CRC risk might be modulated by the rs1573496 (ADH7) polymorphism.

PMID- 23149988
TI  - Record heat may have contributed to a banner year for West Nile virus. Interview
      with Lyle Petersen.

PMID- 23149995
TI  - Adjuvant chemotherapy for resected periampullary adenocarcinoma.

PMID- 23149997
TI  - Treatment with silymarin for hepatitis C virus.

PMID- 23149999
TI  - Reduction of trans-fatty acids from food.

PMID- 23150000
TI  - Reduction of trans-fatty acids from food.

PMID- 23150002
TI  - White matter integrity in the brains of professional soccer players without a
      symptomatic concussion.

PMID- 23150005
TI  - Prevention of fatal opioid overdose.

PMID- 23150006
TI  - Rethinking opioid prescribing to protect patient safety and public health.

PMID- 23150007
TI  - A piece of my mind: The unasked question.

PMID- 23150008
TI  - Structural brain changes in migraine.
AB  - CONTEXT: A previous cross-sectional study showed an association of migraine with
      a higher prevalence of magnetic resonance imaging (MRI)-measured ischemic lesions
      in the brain. OBJECTIVE: To determine whether women or men with migraine (with
      and without aura) have a higher incidence of brain lesions 9 years after initial
      MRI, whether migraine frequency was associated with progression of brain lesions,
      and whether progression of brain lesions was associated with cognitive decline.
      DESIGN, SETTING, AND PARTICIPANTS: In a follow-up of the 2000 Cerebral
      Abnormalities in Migraine, an Epidemiological Risk Analysis cohort, a prospective
      population-based observational study of Dutch participants with migraine and an
      age- and sex-matched control group, 203 of the 295 baseline participants in the
      migraine group and 83 of 140 in the control group underwent MRI scan in 2009 to
      identify progression of MRI-measured brain lesions. Comparisons were adjusted for
      age, sex, hypertension, diabetes, and educational level. The participants in the
      migraine group were a mean 57 years (range, 43-72 years), and 71% were women.
      Those in the control group were a mean 55 years (range, 44-71 years), and 69%
      were women. MAIN OUTCOME MEASURES Progression of MRI-measured cerebral deep white
      matter hyperintensities, infratentorial hyperintensities, and posterior
      circulation territory infarctlike lesions. Change in cognition was also measured.
      RESULTS: Of the 145 women in the migraine group, 112 (77%) vs 33 of 55 women
      (60%) in the control group had progression of deep white matter hyperintensities
      (adjusted odds ratio [OR], 2.1; 95%CI, 1.0-4.1; P = .04). There were no
      significant associations of migraine with progression of infratentorial
      hyperintensities: 21 participants (15%) in the migraine group and 1 of 57
      participants (2%) in the control group showed progression (adjusted OR, 7.7; 95%
      CI, 1.0-59.5; P = .05) or new posterior circulation territory infarctlike
      lesions: 10 of 203 participants (5%) in the migraine group but none of 83 in the
      control group (P = .07). There was no association of number or frequency of
      migraine headaches with progression of lesions. There was no significant
      association of high vs nonhigh deep white matter hyperintensity load with change
      in cognitive scores (-3.7 in the migraine group vs 1.4 in the control group; 95%
      CI, -4.4 to 0.2; adjusted P = .07). CONCLUSIONS: In a community-based cohort
      followed up after 9 years, women with migraine had a higher incidence of deep
      white matter hyperintensities but did not have significantly higher progression
      of other MRI-measured brain changes. There was no association of migraine with
      progression of any MRI-measured brain lesions in men.

PMID- 23150010
TI  - A right wrist lump.

PMID- 23150009
TI  - Genetic variants and associations of 25-hydroxyvitamin D concentrations with
      major clinical outcomes.
AB  - CONTEXT: Lower serum 25-hydroxyvitamin D concentrations are associated with
      greater risks of many chronic diseases across large, prospective community-based
      studies. Substrate 25-hydroxyvitamin D must be converted to 1,25-dihydroxyvitamin
      D for full biological activity, and complex metabolic pathways suggest that
      interindividual variability in vitamin D metabolism may alter the clinical
      consequences of measured serum 25-hydroxyvitamin D. OBJECTIVE: To investigate
      whether common variation within genes encoding the vitamin D-binding protein,
      megalin, cubilin, CYP27B1, CYP24A1, and the vitamin D receptor (VDR) modify
      associations of low 25-hydroxyvitamin D with major clinical outcomes. DESIGN,
      SETTING, AND PARTICIPANTS: Examination of 141 single-nucleotide polymorphisms in
      a discovery cohort of 1514 white participants (who were recruited from 4 US
      regions) from the community-based Cardiovascular Health Study. Participants had
      serum 25-hydroxyvitamin D measurements in 1992-1993 and were followed up for a
      median of 11 years (through 2006). Replication meta-analyses were conducted
      across the independent, community-based US Health, Aging, and Body Composition (n
      = 922; follow-up: 1998-1999 through 2005), Italian Invecchiare in Chianti (n =
      835; follow-up: 1998-2000 through 2006), and Swedish Uppsala Longitudinal Study
      of Adult Men (n = 970; follow-up: 1991-1995 through 2008) cohort studies. MAIN
      OUTCOME MEASURE: Composite outcome of incident hip facture, myocardial
      infarction, cancer, and mortality over long-term follow-up. RESULTS: Interactions
      between 5 single-nucleotide polymorphisms and low 25-hydroxyvitamin D
      concentration were identified in the discovery phase and 1 involving a variant in
      the VDR gene replicated in independent meta-analysis. Among Cardiovascular Health
      Study participants, low 25-hydroxyvitamin D concentration was associated with
      hazard ratios for risk of the composite outcome of 1.40 (95% CI, 1.12-1.74) for
      those who had 1 minor allele at rs7968585 and 1.82 (95% CI, 1.31-2.54) for those
      with 2 minor alleles at rs7968585. In contrast, there was no evidence of an
      association (estimated hazard ratio, 0.93 [95% CI, 0.70-1.24]) among participants
      who had 0 minor alleles at this single-nucleotide polymorphism. CONCLUSION: Known
      associations of low 25-hydroxyvitamin D with major health outcomes may vary
      according to common genetic differences in the vitamin D receptor.

PMID- 23150011
TI  - Multiplicities in the assessment of multiple vitamins: is it too soon to tell men
      that vitamins prevent cancer?

PMID- 23150012
TI  - White matter hyperintensities in migraine: reason for optimism.

PMID- 23150016
TI  - JAMA patient page: Antibiotic resistance.

PMID- 23150017
TI  - Identification of cardiac glycoside molecules as inhibitors of c-Myc IRES
      mediated translation.
AB  - Translation initiation is a fine-tuned process that plays a critical role in
      tumorigenesis. The use of small molecules that modulate mRNA translation provides
      tool compounds to explore the mechanism of translational initiation and to
      further validate protein synthesis as a potential pharmaceutical target for
      cancer therapeutics. This report describes the development and use of a click
      beetle, dual luciferase cell-based assay multiplexed with a measure of compound
      toxicity using resazurin to evaluate the differential effect of natural products
      on cap-dependent or internal ribosome entry site (IRES)-mediated translation
      initiation and cell viability. This screen identified a series of cardiac
      glycosides as inhibitors of IRES-mediated translation using, in particular, the
      oncogene mRNA c-Myc IRES. Treatment of c-Myc-dependent cancer cells with these
      compounds showed a decrease in c-Myc protein associated with a significant
      modulation of cell viability. These findings suggest that inhibition of IRES
      mediated translation initiation may be a strategy to inhibit c-Myc-driven
      tumorigenesis.

PMID- 23150018
TI  - Endoscopic ultrasound guided fine needle aspiration: results are reproducible.

PMID- 23150019
TI  - Epidemiology of viral hepatitis in Saudi Arabia: are we off the hook?
AB  - Some 400 million people worldwide are currently infected with the hepatitis B
      virus (HBV), and the infection is common in the Middle East. Another 170 million
      people around the globe presently live with chronic hepatitis C virus (HCV)
      infection. Both HBV and HCV represent a worldwide epidemic. Despite significant
      decline in the prevalence of HBV and HCV infection in Saudi Arabia, these viral
      diseases cause significant morbidity and mortality, and impose a great burden on
      the country's healthcare system. On the other hand, Saudi epidemiology studies
      have shown that the hepatitis A virus seroprevalence in the country has reduced
      considerably over the past two decades. The progress in mapping the
      epidemiological pattern of viral hepatitis in Saudi Arabia has not only aided our
      understanding of the disease, but has also exposed the small but relevant gaps in
      our identification of the intricate details concerning the disease's clinical
      expression. In this review, we aim to document the timeline of viral hepatitis
      epidemiology in Saudi Arabia, while summarizing the relevant published literature
      on the subject.

PMID- 23150020
TI  - Efficacy of endoscopic ultrasound guided fine needle aspiration in patients with
      solid pancreatic neoplasms.
AB  - BACKGROUND/AIM: Endosonography is a distinct method for evaluating the structural
      lesions of the gastrointestinal (GI) tract, particularly the pancreatobilliary
      region. This procedure has made a fundamental change in the diagnosis of
      pancreatic mass lesion through providing fine needle aspiration. This study aims
      at evaluating the results and efficacy of endoscopic ultrasound fine needle
      aspiration (EUS-FNA) in patients with pancreatic solid mass. PATIENTS AND
      METHODS: The present study is an observational, prospective case series nature,
      evaluated patients with pancreatic solid mass referred to Imam Khomeini
      educational hospital in Tehran for a duration of one year since November 2010. In
      order to determine the false negative cases, the patients were followed-up from 6
      to 12 months. RESULTS: EUS-FNA was conducted on all 53 patients without any
      complication. The majority of patients included in the study were males (68%) and
      81% of patients had a mass in the head of pancreas. The result of cytopathology
      revealed 36 adenocarcinomas (68%), 7 other malignancies (13%), benign lesions
      (6%) and 7 non-diagnostic cases (13%). The frequency of non-diagnostic results
      was significantly high in masses smaller than 3 cm (6 vs. 1, P < 0.002). Patients
      with non-diagnostic result were younger than those with malignant cytopathology
      (52 +/- 7.5 vs. 66 +/- 7.5 years, P < 0.001).. Sensitivity, specificity, positive
      predictive value, negative predictive value and accuracy of this procedure
      concerning Adenocarcinoma were 88%, 100%, 100%, 70% and 90%, respectively.
      CONCLUSION: EUS - FNA is an effective and safe procedure in histopathologic
      diagnosis of pancreatic tumors. This procedure is useful in all pancreatic mass
      cases including resectable and non-resectable ones.

PMID- 23150021
TI  - Role of proteases and antiprotease in the etiology of chronic pancreatitis.
AB  - BACKGROUND/AIM: Chronic pancreatitis (CP) is the progressive and irreversible
      destruction of the pancreas characterized by the permanent loss of endocrine and
      exocrine function. Trypsin, the most important digestive enzyme plays a central
      role in the regulation of all other digestive enzymes. Chymotrypsin, an
      endopeptidase hydrolyzes peptides at amino acids with aromatic side chains. Alpha
      1-antitrypsin is a principal antiprotease which protects the mucosal tissue from
      the proteolytic effects of trypsin and chymotrypsin by the formation of molar
      complexes. The present study is aimed at examining the role of proteases (trypsin
      and chymotrypsin) and anti-protease (alpha1-anti-trypsin) in the etiopathogenesis
      of chronic pancreatitis. PATIENTS AND METHODS: A total of 90 CP patients and 110
      age and sex matched controls were considered for the study. Serum trypsin,
      chymotrypsin and alpha1-anti-trypsin levels were determined prospectively in CP
      patients and compared to healthy controls as described previously. RESULTS: The
      mean activity of trypsin were found to be increased in CP patients (X +/- SD =
      0.82 +/- 0.838) in comparison to normal control group (X +/- SD = 0.55 +/-
      0.328), (P = 0.001). Chymotrypsin activity were also found to be elevated in CP
      patients (X +/- SD = 0.63 +/- 0.278) in comparison to control group (X +/- SD =
      0.39 +/- 0.295), (P = 0.0001). The mean alpha-1-anti-trypsin activity were found
      to be lowered in CP patients (X +/- SD = 0.42 +/- 0.494) in comparison to control
      group (X +/- SD = 0.67 +/- 0.465), with the variation being significant (P =
      0.0003). CONCLUSION: The findings suggest an imbalance in the synthesis and
      degradation of proteolytic enzymes and antiprotease indicating an altered
      aggressive and defensive role in the pathogenesis of chronic pancreatitis.

PMID- 23150022
TI  - Correlation of serology with morphological changes in gastric biopsy in
      Helicobacter pylori infection and evaluation of immunohistochemistry for H.
      pylori identification.
AB  - BACKGROUND/AIM: Helicobacter pylori is implicated in various gastroduodenal
      diseases and many tests are available for its detection. The present study
      attempted to document the morphological changes in the gastric mucosa induced by
      H. pylori colonization and correlate them with the severity of the infection. The
      study also compared various diagnostic tests and evaluated the different staining
      methods used for H. pylori detection, especially immunohistochemical
      identification. PATIENTS AND METHODS: One hundred and two patients with dyspepsia
      were included. Enzyme-linked immunosorbent assay (ELISA) for H. pylori-specific
      immunoglobulin G (IgG), immunoglobulin A (IgA), and immunoglobulin M (IgM) was
      used. Rapid urease test was performed on endoscopic biopsy and it was stained
      with hematoxylin and eosin (H and E), modified Giemsa, and immunohistochemical
      stains. RESULTS: A significant correlation was found between the density of H.
      pylori and severity of gastritis. A significant correlation was observed between
      serology (especially when used in combination, IgG and IgA) and status of H.
      pylori. Immunohistochemical staining enhanced the diagnostic yield of H. pylori
      detection. CONCLUSIONS: Immunohistochemistry (IHC) should be used judiciously,
      whereas simple and economical tests like modified Giemsa should be used routinely
      for the detection of H. pylori. Combined ELISA (IgG and IgA) should be preferred
      over single ELISA. Simultaneous morphological and serological detection of H.
      pylori is preferable as H. pylori may not be detected on morphology alone due to
      its patchy distribution in the stomach.

PMID- 23150023
TI  - Persistent oxidative stress in patients with chronic active hepatitis-C infection
      after antiviral therapy failure.
AB  - BACKGROUND/AIMS: Oxidative stress and hepatocellular pathological changes are
      common associations with chronic hepatitis C virus (CHC) disease. The aim of this
      study was to assess serum antioxidant-oxidant (Redox) balance in patients with
      CHC infection before and after intake of the traditional antiviral therapy
      (pegylated interferon alpha-2b and oral ribavirin). PATIENTS AND METHODS: Blood
      samples from 50 biopsy-proven CHC patients, with no prior anti-viral treatment
      and persistently elevated serum transaminase levels for 6 months, as well as 15
      age- and sex-matched healthy subjects were used for determination of the
      antioxidants: reduced glutathione (GSH), superoxide dismutase (SOD), alpha
      tocopherol and ascorbic acid as well as lipid peroxidation (LPO) index
      (malondialdehyde [MDA]). The measurements were repeated in the diseased group 25
      weeks after pegylated interferon alpha-2b and ribavirin combination therapy.
      RESULTS: Serum levels of bilirubin, aspartate aminotransferase (AST), and alanine
      aminotransferase (ALT) were significantly higher in CHC patients than in the
      control group (P < 0.05). Pretreatment serum MDA values were significantly higher
      in patients with CHC infection than the control group (P < 0.001), while serum
      antioxidant levels were significantly lower (P < 0.001). Responders (10 patients)
      had lower pretreatment serum levels of MDA than non-responders (35 patients) (P <
      0.001). Both groups were comparable for the antioxidant serum levels. There was
      significant negative correlation between serum MDA and serum SOD, GSH, alpha
      tocopherol, and ascorbic acid concentrations in CHC patients. On the other hand,
      there was no correlation between the studied parameters and serum bilirubin,
      albumin, ALT, and AST. CONCLUSIONS: Redox imbalance was detected in patients with
      CHC. Responders had significantly lower levels of MDA than non-responders. Serum
      MDA may be used as a pretreatment predictor of response to antiviral treatment in
      patients with CHC.

PMID- 23150024
TI  - Portal hypertension: effect of early splenic artery ligation on platelets count
      during splenectomy.
AB  - BACKGROUND/AIM: Hypersplenism due to splenic congestion is observed in portal
      hypertensive patients. This study was done to know the change in platelets count
      following early ligation of splenic artery during splenectomy in patients with
      thrombocytopenia due to portal hypertension with a hypothesis that splenic
      decongestion results in increased platelets count; thereby platelet transfusion
      can be avoided. MATERIALS AND METHODS: Patients with platelets count <100,000 per
      mm(3) due to portal hypertension were involved and we followed a protocol of
      ligating splenic artery first, followed by 30 minutes waiting period for splenic
      decongestion. Blood sample was collected at 5 and 30 minutes for the estimation
      of platelets count. RESULTS: Significant rise in platelets was observed after 5
      and 30 minutes of early ligation of splenic artery with mean rise being 23735 +/-
      15417 and 35085 +/- 20458 per mm(3), respectively. The rise in platelets at 30
      minutes was significant when compared with 5 minutes rise with mean platelets
      count being 91661 and 103070 per mm(3) at 5 and 30 minutes, respectively. The
      platelets rise was equal to 4 and 6 units of platelets concentrates,
      respectively. CONCLUSION: Early ligation of splenic artery during splenectomy for
      portal hypertension results in significant rise in platelets after 5 and 30
      minutes. This method conserves platelets and avoids platelets transfusion and its
      complications.

PMID- 23150025
TI  - Intra-arterial CT angiography visualization of arterial supply to inferior vena
      cava tumor thrombus prior to radioembolization of hepatocellular carcinoma.
AB  - Unresectable hepatocellular carcinoma has a high frequency of vascular invasion
      and arterial parasitization. Trans-arterial radioembolization using yttrium-90
      (Y90) microspheres is a possible treatment option. Paramount to its success is
      the meticulous angiographic interrogation of tumor feeding arteries and extra
      hepatic supply. We describe a patient with tumor invasion of the inferior vena
      cava with arterial supply from the right inferior phrenic artery, which was
      exquisitely visualized using intra-arterial computed tomographic angiography
      (IACTA) during the planning technetium-99m macro aggregated albumin phase. This
      technique was useful in planning which artery to administer Y90 microspheres into
      for maximal brachytherapy. Although patient outcome was poor due to significant
      arterio-portal shunting, we believe that IACTA is a useful adjunct to
      conventional digital subtraction angiography in planning radioembolization
      therapy.

PMID- 23150026
TI  - An incidentally discovered asymptomatic para-aortic paraganglioma with Peutz
      Jeghers syndrome.
AB  - Peutz-Jeghers syndrome (PJS) is an autosomal dominant inherited disorder
      characterized by mucocutaneous melanin pigmentation and gastrointestinal (GI)
      tract hamartomatous polyps and an increased risk of malignancy. In addition to
      polyposis, previous studies have reported increased risk of GI and extraGI
      malignancies in PJS patients, compared with that of the general population. The
      most common extraintestinal malignancies reported in previous studies are
      pancreatic, breast, ovarian and testicular cancers.We report the case of a 17
      year-old boy who presented with generalized weakness, recurrent sharp abdominal
      pain and melena, had exploratory laparotomy and ileal resection for ileo-ileal
      intussusception. Pigmentation of the buccal mucosa was noted. An abdominal
      computed tomography scan (CT) revealed multiple polyps in small bowel loops.
      Gastroscopy revealed multiple dimunitive polyps in stomach and pedunculated polyp
      in duodenum. Colonoscopy revealed multiple colonic polyps. Pathological
      examination of the polyps confirmed hamartomas with smooth muscle arborization,
      compatible with Peutz-Jeghers polyps. CT scan guided left para-aortic lymph node
      biopsy revealed the characteristic features of extra-adrenal para-aortic
      paraganglioma. Although cases of various GI and extra GI malignancies in PJS
      patients has been reported, the present case appears to be the first in
      literature in which the PJS syndrome was associated with asymptomatic
      extraadrenal para-aortic paraganglioma. Patients with PJS should be treated by
      endoscopic or surgical resection and need whole-body screening.

PMID- 23150027
TI  - A mysterious cause of stool ova.

PMID- 23150028
TI  - Collective action in the management of a tropical dry forest ecosystem: effects
      of Mexico's property rights regime.
AB  - Dilemmas of natural resources governance have been a central concern for
      scholars, policy makers, and users. Major debates occur over the implications of
      property rights for common resources management. After the Mexican Revolution
      (1910-1917), land was distributed mainly as ejidos conceived as a hereditary but
      unalienable collective form of property. In 1992, a new Agrarian Law was decreed
      that allows individual ownership by removing various restrictions over the
      transfer of land. Scholars have examined the reform mainly focusing on land
      tenure changes and environmental fragmentation. This study examines how the new
      ownership regime is affecting collective decision-making in ejidos located in a
      tropical dry forest (TDF) ecosystem. Information on decision-making processes
      before and after the 1992 reform was gathered through 52 interviews conducted in
      four ejidos selected along a gradient including agricultural, cattle-raising, and
      TDF use. The new individualized land property system reduced collective action in
      ejidos but did not trigger it. Collective action responses to the 1992 reform
      were buffered by self-organization each ejido already had. Heterogeneous users
      who shared a short history and showed little understanding of TDF and low
      dependence on its resources seemed to explain why ejidos have not been able to
      share a sense of community that would shape the construction of institutions for
      the collective management of forest resources. However, when a resource is scarce
      and highly valuable such as water the same users showed capacities for
      undertaking costly co-operative activities.

PMID- 23150029
TI  - Prognostic and predictive markers in medullary thyroid carcinoma.
AB  - Unlike papillary thyroid carcinoma, medullary thyroid carcinoma is insensitive to
      adjuvant treatment with radioactive iodine. The clinical management of patients
      with advanced or metastatic disease remains challenging since no effective
      systemic adjuvant therapy is available. We aimed to identify markers of
      aggressive disease and novel drugable protein targets that would provide systemic
      adjuvant treatment for patients with advanced medullary thyroid carcinoma. We
      therefore examined morphologic features of aggressive behavior and the expression
      of 41 proteins involved in apoptosis, cell cycle, angiogenesis, inflammation,
      cell adhesion, tumor-specific markers, and WNT, SHH, and AKT pathways using
      tissue microarray from 23 patients with medullary thyroid carcinoma. Protein
      expression was determined using computerized image analysis software. Statistical
      analysis was carried out to correlate clinical data with the average score for
      each marker. Angioinvasion proved to be the most reliable predictor of disease
      recurrence and death. The rate of angioinvasion was 43 %. All angioinvasive
      medullary thyroid carcinomas had locoregional and/or distant metastasis; 60 % of
      angioinvasive medullary thyroid carcinomas developed distant metastasis. We
      identified expression of several potentially important protein targets such as
      COX-1/2, Bcl-2a, Gst-pi, Gli-1, Gli-2, Gli-3, and Bmi-1 that may be
      therapeutically targeted in medullary thyroid carcinoma. More importantly, the
      immunohistochemical profile of SSTRs in medullary thyroid carcinoma may also have
      clinical relevance for the administration of peptide receptor radionuclide
      treatment. Successful outcome of clinical trials directed against these novel
      targets would provide much needed systemic adjuvant treatment for patients with
      advanced medullary thyroid carcinoma, and our data suggest the possibility of
      stratifying patients who are likely to require adjuvant therapy before their
      burden of disease precludes successful therapeutic effect.

PMID- 23150031
TI  - An adolescent boy with acute kidney injury and fever. Hemorrhagic fever with
      renal syndrome (HFRS).

PMID- 23150030
TI  - Is obesity a risk factor for chronic kidney disease in children?
AB  - There is a rapid increase worldwide in the prevalence of obesity in adults and
      children. Obesity is not only a comorbidity for chronic kidney disease (CKD) but
      may also be a risk factor for CKD. Epidemiological correlations and
      pathophysiological changes have been observed associating obesity with CKD. Low
      birth weight may be associated with both obesity and low nephron mass, leading to
      CKD later in life. Elevated levels of adipokines, such as leptin and adiponectin,
      in obesity may be factors in CKD pathogenesis and progression. Furthermore,
      various other factors, such as hypertension, increased cardiovascular morbidity,
      insulin resistance, dyslipidemia, and lipotoxicity, may play significant roles in
      the pathogenesis of CKD in obesity. Reduction in obesity, which is a potentially
      modifiable risk factor, might help decrease the burden of CKD in the population.
      Apart from individualized options, community-based interventions have the
      potential to create a strong impact in this condition. 

PMID- 23150033
TI  - Change in evolution.

PMID- 23150035
TI  - Inflammatory bowel disease: the Indian augury.

PMID- 23150034
TI  - Neuroimmunology of the atherosclerotic plaque: a morphological approach.
AB  - Atherosclerosis is a chronic inflammatory process, lasting for several decades
      until the onset of its clinical manifestations. The progression of the
      atherosclerotic lesion to a stable fibrotic plaque, narrowing the vascular lumen,
      or to a vulnerable plaque leading to main vascular complications, is associated
      to the involvement of several cell subpopulations of the innate as well as of the
      adaptive immunity, and to the release of chemokines and pro-inflammatory
      cytokines. Emerging evidence outlines that the cardiovascular risk is dependent
      on stress-mediators influencing cell migration and vascular remodeling. The view
      that atherosclerosis is initiated by monocytes and lymphocytes adhering to
      dysfunctional endothelial cells is substantiated by experimental and clinical
      observations. Macrophages, dendritic cells, T and B lymphocytes, granulocytes
      accumulating into the subendothelial space secrete and are stimulated by soluble
      factors, including peptides, proteases and cytokines acting synergistically. The
      final step of the disease, leading to plaque destabilization and rupture, is
      induced by the release, at the level of the fibrous cap, of metalloproteinases
      and elastases by the activated leukocytes which accumulate locally. Recruitment
      of specific cell subpopulations as well as the progression of atherosclerotic
      lesions towards a stable or an unstable phenotype, are related to the unbalance
      between pro-atherogenic and anti-atherogenic factors. In this connection stress
      hormones deserve particular attention, since their role in vascular remodeling,
      via vascular smooth cell proliferation, as well as in neoangiogenesis, via
      stimulation of endothelial cell proliferation and migration, has been already
      established.

PMID- 23150037
TI  - Molecular evolution: epistasis prevails.

PMID- 23150036
TI  - Text-mining solutions for biomedical research: enabling integrative biology.
AB  - In response to the unbridled growth of information in literature and biomedical
      databases, researchers require efficient means of handling and extracting
      information. As well as providing background information for research, scientific
      publications can be processed to transform textual information into database
      content or complex networks and can be integrated with existing knowledge
      resources to suggest novel hypotheses. Information extraction and text data
      analysis can be particularly relevant and helpful in genetics and biomedical
      research, in which up-to-date information about complex processes involving
      genes, proteins and phenotypes is crucial. Here we explore the latest
      advancements in automated literature analysis and its contribution to innovative
      research approaches.

PMID- 23150039
TI  - Molecular evolution: new layers to recombination patterns.

PMID- 23150040
TI  - Gene regulation: bivalency buffer makes pluripotency connections.

PMID- 23150038
TI  - Studying genomic processes at the single-molecule level: introducing the tools
      and applications.
AB  - To understand genomic processes such as transcription, translation or splicing,
      we need to be able to study their spatial and temporal organization at the
      molecular level. Single-molecule approaches provide this opportunity, allowing
      researchers to monitor molecular conformations, interactions or diffusion
      quantitatively and in real time in purified systems and in the context of the
      living cell. This Review introduces the types of application of single-molecule
      approaches that can enhance our understanding of genome function.

PMID- 23150041
TI  - Gene expression: dynamic omics responses.

PMID- 23150042
TI  - A nanoporous alumina microelectrode array for functional cell-chip coupling.
AB  - The design of electrode interfaces has a strong impact on cell-based
      bioelectronic applications. We present a new type of microelectrode array chip
      featuring a nanoporous alumina interface. The chip is fabricated in a combination
      of top-down and bottom-up processes using state-of-the-art clean room technology
      and self-assembled generation of nanopores by aluminum anodization. The electrode
      characteristics are investigated in phosphate buffered saline as well as under
      cell culture conditions. We show that the modified microelectrodes exhibit
      decreased impedance compared to planar microelectrodes, which is caused by a
      nanostructuring effect of the underlying gold during anodization. The stability
      and biocompatibility of the device are demonstrated by measuring action
      potentials from cardiomyocyte-like cells growing on top of the chip. Cross
      sections of the cell-surface interface reveal that the cell membrane seals the
      nanoporous alumina layer without bending into the sub-50 nm apertures. The
      nanoporous microelectrode array device may be used as a platform for combining
      extracellular recording of cell activity with stimulating topographical cues.

PMID- 23150043
TI  - Randomized trial of a peer resistance skill-building game for Hispanic early
      adolescent girls.
AB  - BACKGROUND: Adolescents can use peer resistance skills to avoid being pressured
      into risky behavior, such as early sexual behavior. Avatar-based virtual reality
      technology offers a novel way to help build these skills. OBJECTIVES: The aims of
      this study were to evaluate the feasibility of an avatar-based virtual reality
      peer resistance skill building game (DRAMA-RAMA), to explore the impact of game
      play on peer resistance self-efficacy, and to assess how positively the game was
      perceived. METHODS: Forty-four low-income early adolescent Hispanic girls were
      assigned randomly to either the intervention (DRAMA-RAMA) or attention control
      game (Wii Dancing With the Stars) condition. All participants were offered a five
      session curriculum that included peer resistance skill content before playing
      their respective game for 15 minutes, once a week, for 2 weeks. Participants
      completed electronic surveys at baseline, after game play, and at 2 months to
      assess demographics, peer resistance self-efficacy, and sexual behavior. They
      also completed a paper-pencil game experience questionnaire immediately after
      game play. Data were analyzed using descriptive statistics, t test, chi-square,
      and analyses of covariance. RESULTS: Separate analyses of covariance showed a
      significant game effect at posttest for the peer resistance self-efficacy measure
      (F = 4.21, p < .05), but not at follow-up (F = 0.01, p = .92). DRAMA-RAMA was
      rated as positively as the Wii Dancing With the Stars (p > .26). DISCUSSION: This
      randomized control trial provides preliminary support for the hypothesis that
      playing an avatar-based virtual reality technology game can strengthen peer
      resistance skills, and early adolescent Hispanic girls will have a positive
      response to this game.

PMID- 23150044
TI  - Risk factors for poor vision-related quality of life among cataract patients.
      Evaluation of baseline data.
AB  - BACKGROUND: Our study aims to investigate the possible risk factors for poor
      vision-related quality of life in patients scheduled to undergo
      phacoemulsification. METHODS: Participants in our study were 220 patients who
      were eligible for phacoemulsification cataract surgery. All participants
      underwent a routine ophthalmological examination and completed the Visual
      Function Questionnaire-25 (VFQ-25), which encompasses 12 subscales and the
      composite score. Sociodemographic and lifestyle parameters were evaluated as
      potential risk factors for low VFQ-25 composite score, as well as subscale
      scores. Multivariate regression analysis was performed. RESULTS: Composite score
      did not exhibit any significant associations. General Health subscale score was
      positively associated with higher educational level. Patients who currently
      worked presented with lower Vision Specific Mental Health subscale score (OR:
      0.33, 95 % CI: 0.18 to 0.63). Vision Specific Role Difficulties subscale score
      was positively associated with exercise (OR: 1.89, 95 % CI: 1.30 to 2.75). Vision
      Specific Dependency subscale score was independently positively associated with
      marital status (married vs single/widowed/divorced, OR: 1.83, 95 % CI: 1.08 to
      3.12) but inversely with current working status (OR: 0.40, 95 % CI: 0.20 to
      0.79). Males exhibited lower Peripheral Vision subscale score compared with
      females (OR: 0.19, 95 % CI: 0.04 to 0.91). CONCLUSIONS: Baseline vision-related
      quality of life in cataract patients presenting for surgery seems affected by
      inherent sociodemographic and lifestyle parameters, such as gender, educational
      level, marital status, current working status and exercise. Therefore, clinicians
      should be aware of the discrepancies that risk factors may confer, and should
      thus focus on the most vulnerable subgroups.

PMID- 23150046
TI  - [Clinical appearance and differential diagnosis of intracranial arterial
      stenoses].
AB  - Intracranial arterial stenoses clinically present as acute, fluctuating or
      recurrent neurological deficits which are caused by hemodynamically impaired
      perfusion of the corresponding area of the brain. The type and the extent of the
      deficit, however, are not only determined by the location of the stenosis but
      also depend on the individual anatomical conditions of the patient, such as the
      degree of collateralization and variants of the circle of Willis.

PMID- 23150045
TI  - Amniotic bands as a cause of congenital anterior staphyloma.
AB  - BACKGROUND: Congenital anterior staphyloma is a rare, complex malformation
      syndrome of the anterior segment. Only a few reports on associated systemic
      malformations have been published. We herein present a rare manifestation of
      congenital anterior staphyloma (CAS) combined with amniotic band disruption
      syndrome (ABS). PATIENT AND METHODS: Shortly after birth, a massive enlargement
      of the left eye was observed in a female child. Furthermore, an extensive
      bilateral congenital cleft lip and cleft alveolar ridge with oblique facial cleft
      extending into the left medial canthal region, coloboma(s) of the left eyelids,
      extensive adhesions between lids and eye bulb, as well as circumferential
      grooves, clubfeet, and terminal transverse defects in both hands and feet were
      present. Due to severe progression of eye bulb protrusion with thinning of the
      sclera, enucleation of the left eye was performed at the age of 3 years in order
      to prevent complications including perforation of the globe and with the aim of
      improving cosmetic aspects. RESULTS: Histopathological examination of the
      enucleated eye disclosed findings typical of congenital anterior staphyloma,
      including massive corneal staphylomatic deformation with superficial
      vascularization and elapsed corneoscleral margin, destruction of Bowman's layer,
      absence of Descemet's layer, corneal endothelium, and angle structures. The lens
      was only partially formed, and had mainly dissolved. The neural retina appeared
      normal. The optic nerve disc revealed a pronounced excavation. Facial clefts, lid
      colobomas, congenital constriction bands, and amputation of distal limbs match
      ABS. This malformation complex develops in early pregnancy, probably prior to 35
      days post conception. CONCLUSION: This is the first report on an association of
      these two rare complex congenital malformations, congenital anterior staphyloma
      and amniotic band syndrome. The anterior staphyloma was unilateral, and related
      to facial clefts and lid coloboma in the area adjacent to the anterior
      staphyloma. Furthermore, the systemic deformities are clearly due to the amniotic
      bands, and the timing of the development of both complex malformations seems to
      be similar. All findings suggest that the presence of amniotic bands is a
      causative factor for all observed abnormalities including anterior staphyloma.

PMID- 23150047
TI  - A long-term follow-up of peripapillary retinoschisis with optic disc hypoplasia.
AB  - Peripapillary and macular retinoschisis are usually associated with optic disc
      pits. We report a rare case of peripapillary retinoschisis with optic disc
      hypoplasia. A 59-year-old woman presented with asthenopia. Her best-corrected
      visual acuity was 20/20 OD. Ophthalmoscopy of the right eye revealed
      peripapillary retinoschisis, optic disc hypoplasia and dilated and tortuous
      radial peripapillary capillaries. There was no obvious optic disc pit or vitreous
      traction on optical coherence tomography (OCT) or fluorescein angiography. OCT
      showed retinoschisis around the optic disc, a thin sheet of fenestrated tissue on
      the optic disc and absence of serous retinal detachment. These findings had been
      almost the same at a previous visit to our hospital 17 years previously.
      Peripapillary retinoschisis may occur in patients with optic disc hypoplasia. We
      report a case in which visual acuity and symptoms did not change significantly
      after 17 years of follow-up. 

PMID- 23150048
TI  - How do we make the Liverpool care pathway's laudable aspirations reality?

PMID- 23150049
TI  - Vibrational spectroscopies for the analysis of cutaneous permeation: experimental
      limiting factors identified in the case of caffeine penetration.
AB  - Caffeine is utilised as a reference for permeation studies in dermatology and
      cosmetology. The present work aimed to monitor the permeation of a caffeine
      solution through the skin. For this purpose, Raman and infrared studies were
      performed. Raman microspectroscopy permitted a dynamic follow-up of the caffeine
      diffusion. In complementary, infrared microimaging provided information of the
      caffeine localization in the skin by applying multivariate statistical processing
      on skin tissue sections. Herein, we prove the possibility of tracking low
      concentrations of caffeine through the skin and we highlight some experimental
      limitations of vibrational spectroscopies.

PMID- 23150050
TI  - Letter to the editor regarding "Simultaneous determination of ?9
      tetrahydrocannabinol and 11-nor-9-carboxy-?9-tetrahydrocannabinol in oral fluid
      using isotope dilution liquid chromatography tandem mass spectrometry".

PMID- 23150051
TI  - Comparison of different extraction methods for simultaneous determination of B
      complex vitamins in nutritional yeast using LC/MS-TOF and stable isotope dilution
      assay.
AB  - The application of LC/MS-TOF method combined with stable isotope dilution assay
      was studied for determination of thiamine, riboflavin, nicotinamide, nicotinic
      acid, pantothenic acid, pyridoxal, and pyridoxine in food. Nutritional yeast
      powder was used as a model food matrix. Acid extraction was compared with various
      enzymatic treatments in ammonium formate buffer to find a suitable method for the
      conversion of more complex vitamers into the same forms as the used isotope
      labeled internal standards. The enzyme preparations alpha-amylase, takadiastase,
      beta-glucosidase, and acid phosphatase were all able to liberate thiamine and
      riboflavin. The diastatic enzyme preparations alpha-amylase and takadiastase also
      expressed proteolytic side activities resulting in the formation of small
      peptides which interfered with the mass spectra of thiamine and riboflavin.
      Liberation of nicotinamide and pantothenic acid from NAD(+) and CoA,
      respectively, could not be achieved with any of the studied enzyme preparations.
      Hydrochloric acid extraction at 121  degrees C for 30 min was found to be
      destructive to pantothenic acid, but increased the liberation of pyridoxal.

PMID- 23150052
TI  - In situ electrochemical evaluation of anticancer drug temozolomide and its
      metabolites-DNA interaction.
AB  - Temozolomide (TMZ) is an antineoplastic alkylating agent with activity against
      serious and aggressive types of brain tumours. It has been postulated that TMZ
      exerts its antitumor activity via its spontaneous degradation at physiological
      pH. The in vitro evaluation of the interaction of TMZ and its final metabolites,
      5-aminoimidazole-4-carboxamide (AIC) and methyldiazonium ion, with double
      stranded DNA (dsDNA) was studied using differential pulse voltammetry at a glassy
      carbon electrode. The DNA damage was electrochemically detected following the
      changes in the oxidation peaks of guanosine and adenosine residues. The results
      obtained revealed the decrease of the dsDNA oxidation peaks with incubation time,
      showing that TMZ and AIC/methyldiazonium ion interact with dsDNA causing its
      condensation. Furthermore, the experiments of the in situ TMZ and
      AIC/methyldiazonium ion-dsDNA interaction using the multilayer dsDNA
      electrochemical biosensor confirmed the condensation of dsDNA caused by these
      species and showed evidence for a specific interaction between the guanosine
      residues and TMZ metabolites, since free guanine oxidation peak was detected. The
      oxidative damage caused to DNA bases by TMZ metabolites was also detected
      electrochemically by monitoring the appearance of the 8-oxoguanine/2,8
      dyhydroxyadenine oxidation peaks. Nondenaturing agarose gel electrophoresis of
      AIC/methyldiazonium ion-dsDNA samples confirmed the occurrence of dsDNA
      condensation and oxidative damage observed in the electrochemical results. The
      importance of the dsDNA-electrochemical biosensor in the in situ evaluation of
      TMZ-dsDNA interactions is clearly demonstrated.

PMID- 23150053
TI  - Replicating distinctive facial features in lineups: identification performance in
      young versus older adults.
AB  - Criminal suspects with distinctive facial features, such as tattoos or bruising,
      may stand out in a police lineup. To prevent suspects from being unfairly
      identified on the basis of their distinctive feature, the police often manipulate
      lineup images to ensure that all of the members appear similar. Recent research
      shows that replicating a distinctive feature across lineup members enhances
      eyewitness identification performance, relative to removing that feature on the
      target. In line with this finding, the present study demonstrated that with young
      adults (n = 60; mean age = 20), replication resulted in more target
      identifications than did removal in target-present lineups and that replication
      did not impair performance, relative to removal, in target-absent lineups. Older
      adults (n = 90; mean age = 74) performed significantly worse than young adults,
      identifying fewer targets and more foils; moreover, older adults showed a minimal
      benefit from replication over removal. This pattern is consistent with the
      associative deficit hypothesis of aging, such that older adults form weaker links
      between faces and their distinctive features. Although replication did not
      produce much benefit over removal for older adults, it was not detrimental to
      their performance. Therefore, the results suggest that replication may not be as
      beneficial to older adults as it is to young adults and demonstrate a new
      practical implication of age-related associative deficits in memory.

PMID- 23150055
TI  - Iron deficiency: what are the future trends in diagnostics and therapeutics?

PMID- 23150054
TI  - Quantitative proteomics reveals that the specific methyltransferases Txr1p and
      Ezl2p differentially affect the mono-, di- and trimethylation states of histone
      H3 lysine 27 (H3K27).
AB  - Nuclear DNA in eukaryotic cells is assembled into the hierarchical chromatin
      structure via a process that is dynamically affected by the combinatorial set of
      post-translational modifications (PTMs) of histones in a dynamic manner
      responsive to physiological and environmental changes. The precise quantification
      of these complex modifications is challenging. Here we present a robust MS-based
      quantitative proteomics method for studying histone PTMs using (15)N
      metabolically labeled histones as the internal reference. Using this approach, we
      identified Tetrahymena trithorax related 1 (Txr1p) as a histone methyltransferase
      in Tetrahymena thermophila and characterized the relationships of the Txr1p and
      Ezl2p methyltransferases to histone H3 modification. We identified 32 PTMs in
      more than 60 tryptic peptides from histone H3 of the ciliate model organism
      Tetrahymena thermophila, and we quantified them (average coefficient of
      variation: 13%). We examined perturbations to histone modification patterns in
      two knockout strains of SET-domain-containing histone methyltransferases (HMT).
      Knockout of TXR1 led to progressively decreased mono-, di-, and tri-methylation
      of H3K27 and apparent reduced monomethylation of H3K36 in vivo. In contrast, EZL2
      knockout resulted in dramatic reductions in both di- and tri-methylation of H3K27
      in vivo, whereas the levels of monomethylation of H3K27 increased significantly.
      This buildup of monomethyl H3K27 is consistent with its role as a substrate for
      Ezl2p. These results were validated via immunoblotting using modification site
      specific antibodies. Taken together, our studies define Txr1p as an H3K27
      monomethylation-specific HMT that facilitates the buildup of H3K27 di- and
      trimethylation by the canonical H3K27-specific HMT, Ezl2p. Our studies also
      delineate some of the interdependences between various H3 modifications, as
      compensatory increases in monomethylation at H3K4, H3K23, and H3K56 were also
      observed for both TXR1 and ELZ2 mutants.

PMID- 23150056
TI  - Cancer chemoprevention: successes and failures.
AB  - BACKGROUND: Cancer has traditionally been considered a single disease, but it is
      now known to be far more complex, with an unfolding etiology. In less than 2
      centuries, hundreds--if not thousands--of drugs for the treatment of cancer and
      for palliative care have been developed and tested, with 143 having achieved
      approval by the US Food and Drug Administration (MediLexicon International;
      "Cancer Drugs & Oncology Drugs," http://www.medilexicon.com/drugs
      list/cancer.php). Just 13 agents have been approved, however, for treating
      precancerous lesions or for reducing risk. CONTENT: Nonsteroidal antiinflammatory
      drugs, vitamins, food constituents and spice components, antidiabetic drugs,
      omega-3 fatty acids, and fiber are just a few of the many classes of compounds
      that have been tested for their cancer-preventive potential. We highlight some of
      the agents that have been scrutinized by way of randomized clinical trials in
      humans for their cancer prevention potential. We summarize the major definitive
      cancer chemoprevention studies that (a) were successful in demonstrating efficacy
      and ultimately received regulatory approval; (b) were not successful in
      demonstrating efficacy or had unacceptable toxicities, but from which the field
      has learned important lessons; and (c) showed compelling efficacy against
      surrogate end points but failed to achieve regulatory approval because of a lack
      of consensus regarding the relevance of those end points to clinical benefit.
      SUMMARY: Chemopreventive studies have provided new insights into early disease
      pathogenesis, stimulated new risk assessments and models, fostered important
      research in end point biomarkers, and led to 13 approved agents. The development
      of safe and effective chemopreventive agents holds tremendous potential for
      reducing the burden of cancer.

PMID- 23150057
TI  - New opportunities from the cancer metabolome.
AB  - BACKGROUND: Metabolomics, the study of all metabolites produced in the body,
      which often includes flora and drug metabolites, is the omics approach that can
      be considered most closely related to a patient's phenotype. Metabolomics has a
      great and largely untapped potential in the field of oncology, and the analysis
      of the cancer metabolome to identify biofluid markers and novel druggable targets
      can now be undertaken in many research laboratories. CONTENT: The cancer
      metabolome has been used to identify and begin to evaluate potential biomarkers
      and therapeutic targets in a variety of malignancies, including breast, prostate,
      and kidney cancer. We discuss the several standard techniques for metabolite
      separation and identification, with their potential problems and drawbacks.
      Validation of biomarkers and targets may entail intensive use of labor and
      technology and generally requires a large number of study participants as well as
      laboratory validation studies. The field of pharmacometabolomics, in which
      specific therapies are chosen on the basis of a patient's metabolomic profile,
      has shown some promise in the translation of metabolomics into the arena of
      personalized medicine. SUMMARY: The relatively new approach using metabolomics
      has just begun to enter the mainstream of cancer diagnostics and therapeutics. As
      this field advances, metabolomics will take its well-deserved place next to
      genomics, transcriptomics, and proteomics in both clinical and basic research in
      oncology.

PMID- 23150058
TI  - The riddle of protein diagnostics: future bleak or bright?

PMID- 23150059
TI  - The stem cell marker prominin-1/CD133 interacts with vascular endothelial growth
      factor and potentiates its action.
AB  - Prominin-1, a pentaspan transmembrane protein, is a unique cell surface marker
      commonly used to identify stem cells, including endothelial progenitor cells and
      cancer stem cells. However, recent studies have shown that prominin-1 expression
      is not restricted to stem cells but also occurs in modified forms in many mature
      adult human cells. Although prominin-1 has been studied extensively as a stem
      cell marker, its physiological function of the protein has not been elucidated.
      We investigated prominin-1 function in two cell lines, primary human endothelial
      cells and B16-F10 melanoma cells, both of which express high levels of prominin
      1. We found that prominin-1 directly interacts with the angiogenic and tumor
      survival factor vascular endothelial growth factor (VEGF) in both the primary
      endothelial cells and the melanoma cells. Knocking down prominin-1 in the
      endothelial cells disrupted capillary formation in vitro and decreased
      angiogenesis in vivo. Similarly, tumors derived from prominin-1 knockdown
      melanoma cells had a reduced growth rate in vivo. Further, melanoma cells with
      knocked down prominin-1 had diminished ability to interact with VEGF, which was
      associated with decreased bcl-2 protein levels and increased apoptosis. In vitro
      studies with soluble prominin-1 showed that it stabilized dimer formation of
      VEGF164, but not VEGF121. Taken together, our findings support the notion that
      prominin-1 plays an active role in cell growth through its ability to interact
      and potentiate the anti-apoptotic and pro-angiogenic activities of VEGF.
      Additionally, prominin-1 promotes tumor growth by supporting angiogenesis and
      inhibiting tumor cell apoptosis.

PMID- 23150060
TI  - Internal hernia through the foramen of Winslow: the "narrowed portal vein" sign
      on abdominal CT.
AB  - We report a case of ileal internal hernia through the foramen of Winslow into the
      lesser sac. Preoperative computed tomography (CT) demonstrated that the herniated
      ileum, which showed a closed-loop obstruction, was located behind the portal
      vein, and the vein was subsequently compressed and narrowed by the herniated
      ileum. We found that similar cases in the literature of Winslow's foramen hernias
      that caused portal vein compression; however, portal vein narrowing has not been
      described as a characteristic CT finding. The narrowed portal vein sign could be
      useful in diagnosing the hernia through the foramen of Winslow.

PMID- 23150061
TI  - On the universality of the living: a few epistemological notes.

PMID- 23150062
TI  - Factors associated with change in aerobic capacity following an exercise program
      for individuals with stroke.
AB  - OBJECTIVE: Community exercise programs are effective in improving aerobic
      capacity after stroke, but individual variability in training responses has not
      previously been studied. This study examined explanatory factors for post-program
      responses in aerobic capacity (VO2peak) with respect to training parameters and
      participant characteristics. DESIGN: Secondary analysis of data from a
      prospective cohort study. SUBJECTS: Thirty-two participants, mean age 63 years
      (standard deviation (SD) 13), 29 months (SD 26) post-stroke. METHOD: Following a
      6-month community exercise program, multivariate regression analysis was
      performed to assess for correlates with change in VO2peak with respect to
      training parameters (exercise duration and intensity) and participant
      characteristics (lower limb and balance impairment, aerobic and walking
      capacity). RESULTS: The mean improvement in VO2peak was 11% (SD 19), but
      individually, changes ranged from 32% decline to 56% improvement. Regression
      analysis revealed that only 2 variables, baseline aerobic capacity and balance
      impairment, accounted for the training-related change in VO2peak (R2 = 0.20, p =
      0.045). CONCLUSIONS: There is considerable inter-individual variability in stroke
      exercise program responses in aerobic capacity. Lower baseline aerobic capacity
      and better balance were associated with greater training-related improvements in
      VO2peak. Identifying individuals who are more likely to respond to exercise
      programs may inform future work in establishing effective interventions suited
      for different subsets of the stroke population.

PMID- 23150064
TI  - Exposure to heavy metals and polycyclic aromatic hydrocarbons and DNA damage in
      taiwanese traffic conductors.
AB  - BACKGROUND: Exposure to traffic-related air pollutants, including polycyclic
      aromatic hydrocarbons (PAH) and heavy metals, has been associated with the
      etiology and prognosis of many illnesses. However, the specific causal agents and
      underlying mechanisms for different health outcomes remain unclear. The aims of
      this study were to assess the relations between urinary biomarkers of exposure to
      PAHs (1-hydroxypyrene-glucuronide, 1-OHPG) and heavy metals (cadmium, Cd; nickel,
      Ni; arsenic, As; lead, Pb; and copper, Cu) and the effect of their interaction on
      DNA damage (8-oxo-7,8-dihydro-guanine, 8-oxodG). METHODS: We recruited 91 traffic
      conductors and 53 indoor office workers between May 2009 and June 2011 in Taipei,
      Taiwan. Postshift urine samples from 2 consecutive days were analyzed for 1-OHPG,
      Cd, Ni, As, Pb, Cu, and 8-oxodG. To estimate the effects from PAHs and metals on
      DNA damage, we constructed a linear mixed model adjusted for confounding
      variables. RESULTS: We found that urinary 1-OHPG and Cd levels were independent
      predictors of urinary 8-oxodG levels (beta = 0.112; P = 0.015 for 1-OHPG; beta =
      0.138; P = 0.031 for urinary Cd). The joint effect of urinary 1-OHPG and Cd
      levels was associated with urinary 8-oxodG levels (P = 0.001). CONCLUSIONS: Co
      exposure to environmental PAHs and Cd could cause oxidative DNA damage. IMPACT:
      These findings suggest that the additive interaction between exposure to
      environmental PAHs and Cd could enhance the burden of oxidative stress.

PMID- 23150063
TI  - Postdiagnosis alcohol consumption and breast cancer prognosis in the after breast
      cancer pooling project.
AB  - BACKGROUND: Alcohol consumption is an established risk factor for incident breast
      cancer. However, its role in breast cancer prognosis remains unclear. METHODS: We
      conducted an investigation of postdiagnosis alcohol consumption with recurrence
      and mortality among 9,329 breast cancer patients in the After Breast Cancer
      Pooling Project. Women were diagnosed from 1990 to 2006 with AJCC Stage I-III
      breast tumors from three prospective US cohorts. Alcohol intake was assessed at
      cohort entry (mean 2.1 years postdiagnosis) using a food frequency questionnaire.
      HR and 95% confidence intervals (CI) were estimated using delayed entry Cox
      proportional hazards models with adjustment for known prognostic factors.
      RESULTS: After a mean follow-up of 10.3 years, 1,646 recurrences and 1,543 deaths
      were ascertained. 5,422 women (58%) were considered drinkers (>=0.36 g/day of
      alcohol, >=0.25 drinks/week) with a median of 5.3 g/day. Overall, compared with
      nondrinking, regular alcohol intake (>=6.0 g/day) was not associated with risk of
      recurrence (HR for 6 to less than 12 g/day, 1.03; 95% CI, 0.86-1.24; HR for 12 to
      less than 24 g/day, 1.12; 95% CI, 0.93-1.34; HR for >=24 g/day, 1.04; 95% CI,
      0.84-1.31). However, risk varied significantly by menopausal status (P for
      interaction < 0.05). Postmenopausal women who regularly consumed alcohol (>=6.0
      g/day) had increased risk of recurrence (HR, 1.19; 95% CI, 1.01-1.40). Alcohol
      intake was not associated with mortality. CONCLUSIONS: Regular alcohol
      consumption was not associated with breast cancer recurrence and total mortality
      overall, yet recurrence risk was only elevated in postmenopausal women. IMPACT:
      The association between alcohol intake and recurrence may depend on menopausal
      status at breast cancer diagnosis.

PMID- 23150065
TI  - A high-content imaging workflow to study Grb2 signaling complexes by expression
      cloning.
AB  - Signal transduction by growth factor receptors is essential for cells to maintain
      proliferation and differentiation and requires tight control. Signal transduction
      is initiated by binding of an external ligand to a transmembrane receptor and
      activation of downstream signaling cascades. A key regulator of mitogenic
      signaling is Grb2, a modular protein composed of an internal SH2 (Src Homology 2)
      domain flanked by two SH3 domains that lacks enzymatic activity. Grb2 is
      constitutively associated with the GTPase Son-Of-Sevenless (SOS) via its N
      terminal SH3 domain. The SH2 domain of Grb2 binds to growth factor receptors at
      phosphorylated tyrosine residues thus coupling receptor activation to the SOS-Ras
      MAP kinase signaling cascade. In addition, other roles for Grb2 as a positive or
      negative regulator of signaling and receptor endocytosis have been described. The
      modular composition of Grb2 suggests that it can dock to a variety of receptors
      and transduce signals along a multitude of different pathways(1-3). Described
      here is a simple microscopy assay that monitors recruitment of Grb2 to the plasma
      membrane. It is adapted from an assay that measures changes in sub-cellular
      localization of green-fluorescent protein (GFP)-tagged Grb2 in response to a
      stimulus(4-6). Plasma membrane receptors that bind Grb2 such as activated
      Epidermal Growth Factor Receptor (EGFR) recruit GFP-Grb2 to the plasma membrane
      upon cDNA expression and subsequently relocate to endosomal compartments in the
      cell. In order to identify in vivo protein complexes of Grb2, this technique can
      be used to perform a genome-wide high-content screen based on changes in Grb2 sub
      cellular localization. The preparation of cDNA expression clones, transfection
      and image acquisition are described in detail below. Compared to other genomic
      methods used to identify protein interaction partners, such as yeast-two-hybrid,
      this technique allows the visualization of protein complexes in mammalian cells
      at the sub-cellular site of interaction by a simple microscopy-based assay. Hence
      both qualitative features, such as patterns of localization can be assessed, as
      well as the quantitative strength of the interaction.

PMID- 23150066
TI  - Potent activity against multidrug-resistant Mycobacterium tuberculosis of alpha
      mangostin analogs.
AB  - A new series of mangostin analogs of natural alpha-mangostin from mangosteen was
      prepared and their antimycobacterial activity was evaluated in vitro against
      Mycobacterium tuberculosis H(37)Ra. The results showed that the monoalkyl
      tetrahydro alpha-mangostin analogs displayed increased antimycobacterial activity
      as compared with the lead natural xanthone, alpha-mangostin. Among the tested
      compounds, 6-methoxytetrahydro alpha-mangostin (16) exhibited the most potent
      antimycobacterial activity with minimum inhibitory concentration (MIC) of 0.78
      ug/mL. The activity of the monoalkylated and monoacylated tetrahydro alpha
      mangostins decreases as the length of carbon chain increases. The methyl ether
      analog was also active against the multidrug-resistant (MDR) strains with
      pronounced MICs of 0.78-1.56 ug/mL.

PMID- 23150067
TI  - Design, synthesis and anticancer activity of N(3),N(11)-bis(2-hydroxyethyl)-14
      aryl-14H-dibenzo[a,j]xanthenes-3,11-dicarboxamide.
AB  - A series of novel N(3),N(11)-bis(2-hydroxyethyl)-14-aryl-14H
      dibenzo[a,j]xanthenes-3,11-dicarboxamide, three N(3),N(11)-bis(2-hydroxyethyl)-14
      aryl-14H-dibenzo[a,j]xanthene-3,11-dimethanamine derivatives and their
      intermediates 14-aryl-14H-dibenzo[a,j]xanthenes-3,11-dicarboxylic acid, were
      synthesized, and the structures of which were characterized by (1)H-NMR, (13)C
      NMR, high resolution (HR)-MS, and IR spectra. The antitumor activities of these
      molecules were evaluated on five cancer cell lines. The results of in vitro assay
      against human hepatocellular carcinoma cell lines (SK-HEP-1 and HepG2 and SMMC
      7721 cells), acute promyelocytic leukemia NB4 cells and uterine cervix cancer
      HeLa cells, show several compounds to be endowed with cytotoxicity in micromolar
      to submicromolar range. The carboxamide derivatives 6c and 6e exhibitted good
      inhibition on NB4 cancer cells, and the IC(50) values of which were 0.82 uM and
      0.96 uM, respectively, much lower than 5.01 uM of the positive control As(2)O(3).
      Flow cytometric analysis results revealed that compounds 6e and 6f may induce
      tumor cell apoptosis.

PMID- 23150068
TI  - Integrated care: treatment initiation following positive depression screens.
AB  - BACKGROUND: Primary Care-Mental Health Integration (PC-MHI) may improve mental
      health services access and continuity of care. OBJECTIVE: To assess whether
      receipt of integrated PC-MHI services on the date of an initial positive
      depression screen influences receipt of depression treatment among primary care
      (PC) patients in the Veterans Health Administration. DESIGN: Retrospective cohort
      study. SUBJECTS: Thirty-six thousand, two hundred and sixty-three PC patients
      with positive depression screens between October 1, 2009 and September 30, 2010.
      MAIN MEASURES: Subjects were assessed for depression diagnosis and initiation of
      antidepressants or psychotherapy on the screening day, within 12 weeks, and
      within 6 months. Among individuals with PC encounters on the screening day,
      setting of services received that day was categorized as PC only, PC-MHI, or
      Specialty Mental Health (SMH). Using multivariable generalized estimating
      equations (GEE) logistic regression, we assessed likelihood of treatment
      initiation, adjusting for demographic and clinical measures, including depression
      screening score. KEY RESULTS: Patients who received same-day PC-MHI services were
      more likely to initiate psychotherapy (OR: 8.16; 95 % CI: 6.54-10.17) and
      antidepressant medications (OR: 2.33, 95 % CI: 2.10-2.58) within 12 weeks than
      were those who received only PC services on the screening day. CONCLUSIONS:
      Receipt of same-day PC-MHI may facilitate timely receipt of depression treatment.

PMID- 23150069
TI  - A missed opportunity.

PMID- 23150071
TI  - Flexible single-walled carbon nanotube/polycellulose papers for lithium-ion
      batteries.
AB  - Flexible and highly conductive single-walled carbon nanotube/polycellulose papers
      (SWCNT/PPs) were developed as current collectors for lithium-ion batteries by a
      simple and scalable process. The flexible electrodes based on SWCNT/PP conductors
      consisted of a unique three-dimensional interwoven structure of electrode
      materials and cellulose fibers with CNTs and exhibited flexibility, good
      electrochemical performance and excellent cyclic stability. Full cells using
      Li(4)Ti(5)O(12) and LiFePO(4) electrodes based on SWCNT/PPs showed a first
      discharge capacity of 153.5 mA h g(-1) with Coulombic efficiencies of 90.6% at
      0.1 C and discharge capacity of 102.6 mA h g(-1) at high rate (10 C). Full cells
      based SWCNT/PP conductors showed higher capacities and lower electrochemical
      interfacial resistance compared to metallic current collectors. Half cells using
      anatase TiO(2) hierarchical spheres based on SWCNT/PP conductors also exhibited
      outstanding electrochemical performance, verifying the stability of SWCNT/PP
      conductors to various electrode materials. Our results demonstrated the potential
      versatility of composite electrodes and conductive SWCNT/PPs for flexible and
      portable micropower devices.

PMID- 23150070
TI  - The Interconnections Project: development and evaluation of a community-based
      depression program for African American violence survivors.
AB  - BACKGROUND: Multi-faceted depression care programs based within the healthcare
      system have been found to be effective, but may not fully address the needs of
      African American Intimate Partner Violence (IPV) survivors, many of whom are not
      seeking depression care in healthcare settings. OBJECTIVES: To develop and
      evaluate a multifaceted, community-based depression care program (the
      Interconnections Project) for African American women with a history of IPV.
      METHODS: We used a community-based participatory research (CBPR) approach to
      develop, implement, and evaluate the intervention. Participants were African
      American women who had current depressive symptoms and a lifetime history of IPV.
      They participated in a 6-month intervention where a peer advocate provided
      education, skills training, and case management services, and used Motivational
      Interviewing to support self-management behaviors. We conducted pre-intervention
      and post-intervention assessments using quantitative and qualitative data.
      RESULTS: Fifty-nine women participated, with 92 % attending any sessions and 51 %
      attending at least 6 h of intervention activities. Intervention changes made to
      better accommodate participants' unpredictable schedules improved participation
      rates. Participants noted high levels of satisfaction with the program. There
      were significant improvements in depression severity (PHQ-9 13.9 to 7.9, p <
      0.001), self-efficacy, self-management behaviors, and self-esteem (all p <
      0.001), but no increase in use of antidepressants. Common themes related to why
      the program was helpful included that the program was by and for African American
      women, that it fostered trust, and that it taught self-management strategies with
      practical, lasting value. CONCLUSION: Culturally specific, community-based
      interventions led by peer advocates may be a promising way to help African
      American IPV survivors effectively address depression.

PMID- 23150072
TI  - World Health Organization Global Initiative for Emergency and Essential Surgical
      Care: 2011 and beyond.

PMID- 23150073
TI  - In vitro metabolism of grandisin, a lignan with anti-chagasic activity.
AB  - Tetrahydrofuran lignans represent a well-known group of phenolic compounds
      capable of acting as antiparasitic agents. In the search for new medicines for
      the treatment of Chagas disease, one promising compound is grandisin which has
      shown significant activity on trypomastigote forms of Trypanosoma cruzi. In this
      work, the in vitro metabolism of grandisin was studied in the pig cecum model and
      by biomimetic phase I reactions, aiming at an ensuing a preclinical
      pharmacokinetic investigation. Although grandisin exhibited no metabolization by
      the pig microbiota, one putative metabolite was formed in a biomimetic model
      using Jacobsen catalyst. The putative metabolite was tested against T. cruzi
      revealing loss of activity in comparison to grandisin.

PMID- 23150074
TI  - Cytotoxic dihydrothiophene-condensed chromones from marine-derived fungus
      Penicillium oxalicum.
AB  - Two new dihydrothiophene-condensed chromones and a new natural chromone, namely
      oxalicumones A-C (1-3), respectively, were isolated from a culture broth of a
      marine-derived fungus Penicillium oxalicum SCSGAF 0023, Meripilaceae family. The
      structures of 1-3 and acetylated derivatives of 1 (4-7) were elucidated on the
      basis of spectroscopic methods and chemical reactions. The absolute configuration
      of 1 was established by using the modified Mosher ester method and circular
      dichroism data of in situ formed [Rh2(OCOCF3)4] and [Mo2(OAc)4] complexes. (R)
      MTPA ester of 1 showed cytotoxicity against A375, SW-620, and HeLa carcinoma cell
      lines with IC50 values of 8.9, 7.8, and 18.4 uM, respectively. Compound 1
      displayed cytotoxicity against A375 and SW-620 cell lines with IC50 values of
      11.7 and 22.6 uM, respectively. The structure-biological activity relationship of
      1 is discussed.

PMID- 23150075
TI  - Neuroprotective lignans from the stems of Schisandra glaucescens.
AB  - Two new tetrahydrofuran lignans, schiglaucin A and B (1-2), together with eight
      known analogues (3-10), were isolated from the stems of Schisandra glaucescens
      Diels. Their structures were elucidated on the basis of spectroscopic techniques
      (HRESIMS, UV, IR, NMR, and CD experiments). All of the compounds were tested for
      their neuroprotective activities against H2O2- and CoCl2-induced cell injuries in
      SH-SY5Y cells, respectively. Compounds 1-10 showed significant neuroprotective
      effects against H2O2-induced SH-SY5Y cell death, while compounds 1-5 and 8-10
      exhibited significant neuroprotective effects against CoCl2-induced SH-SY5Y cell
      injury.

PMID- 23150076
TI  - Myrtucommulone from Myrtus communis: metabolism, permeability, and systemic
      exposure in rats.
AB  - Nonsteroidal anti-inflammatory drug intake is associated with a high prevalence
      of gastrointestinal side effects, and severe cardiovascular adverse reactions
      challenged the initial enthusiasm in cyclooxygenase-2 inhibitors. Recently, it
      was shown that myrtucommulone, the active ingredient of the Mediterranean shrub
      Myrtus communis, dually and potently inhibits microsomal prostaglandin E2
      synthase-1 and 5-lipoxygenase, suggesting a substantial anti-inflammatory
      potential. However, one of the most important prerequisites for the anti
      inflammatory effects in vivo is sufficient bioavailability of myrtucommulone.
      Therefore, the present study was aimed to determine the permeability and
      metabolic stability in vitro as well as the systemic exposure of myrtucommulone
      in rats. Permeation studies in the Caco-2 model revealed apparent permeability
      coefficient values of 35.9 . 10-6 cm/s at 37  degrees C in the apical to
      basolateral direction, indicating a high absorption of myrtucommulone. In a pilot
      rat study, average plasma levels of 258.67 ng/mL were reached 1 h after oral
      administration of 4 mg/kg myrtucommulone. We found that myrtucommulone undergoes
      extensive phase I metabolism in human and rat liver microsomes, yielding
      hydroxylated and bihydroxylated as well as demethylated metabolites.
      Physiologically-based pharmacokinetic modeling of myrtucommulone in the rat
      revealed rapid and extensive distribution of myrtucommulone in target tissues
      including plasma, skin, muscle, and brain. As the development of selective
      microsomal prostaglandin E2 synthase-1 inhibitors represents an interesting
      alternative strategy to traditional nonsteroidal anti-inflammatory drugs and
      cyclooxygenase-2 inhibitors for the treatment of chronic inflammation, the
      present study encourages further detailed pharmacokinetic investigations on
      myrtucommulone.

PMID- 23150077
TI  - Diuretic effect of compounds from Hibiscus sabdariffa by modulation of the
      aldosterone activity.
AB  - Recent studies of Hibiscus sabdariffa Linn. have demonstrated that it presents
      diuretic, natriuretic, and potassium sparing effects. However, the mechanism that
      induces these effects has not yet been elucidated. The aim of this study was to
      explore the possible mechanism of action for the diuretic effect of Hibiscus
      sabdariffa extract and its fractions.The aqueous extract from this plant and the
      fractions obtained with solvents of different polarities were administered to
      adrenalectomized rats, and the diuretic effect was measured in the presence of
      deoxycorticosterone acetate (aldosterone analog).The effect on renal filtration
      was also evaluated in an in situ kidney model, and finally, the effect of
      diuretic active extracts on gene expression of the alpha subunit from the
      transporter (alphaENaC) of renal epithelial cell was quantified. The subsequent
      results were obtained: The aqueous extract of Hibiscus sabdariffa presented the
      following chemical composition, 32.4 mg/g delphinidin-3-O-sambubioside, 11.5 mg/g
      cyanidin-3-O-sambubioside, 11.5 mg/g quercetin, and chlorogenic acid 2.7 mg/g.
      The concentration of anthocyanins was diminished until disappearance due to
      decrease of the polarity of the solvents used in the extraction process, in
      contrast to the flavonoids and chlorogenic acid, which had their concentration
      increased. The diuretic effect caused by adrenalectomy in rats was reversed by
      deoxycorticosterone acetate activity. However, the effect of deoxycorticosterone
      acetate was antagonized by spironolactone, the aqueous extract of Hibiscus
      sabdariffa, and the acetonitrile : methanol 5 : 5 mixture extract, administered
      orally. A similar effect was observed on renal filtration obtained from the
      isolated kidney model.When the gene expression levels of alphaENaC was measured
      in adrenalectomized rats, it was observed that spironolactone, the aqueous
      extract of Hibiscus sabdariffa, the acetonitrile : methanol 5 : 5 mixture, as
      well as the acetonitrile extract significantly decreased the expression of this
      protein.The conclusion of this work is that the diuretic, natriuretic, and
      potassium sparing effects of Hibiscus sabdariffa are due in part to the
      modulation of aldosterone activity by the presence in the extract of this plant
      of compounds potentially responsible for this modulation, as anthocyanins,
      flavonoids, and chlorogenic acid.

PMID- 23150078
TI  - Phytoecdysteroids from the stem bark of Vitex doniana and their anti-inflammatory
      effects.
AB  - With reference to the ethnopharmacological significance of Vitex doniana Sweet
      (Lamiaceae) leaves in the treatment of stomach and rheumatic pains as well as
      inflammatory disorders, biological studies on its stem bark extracts have also
      reported anti-inflammatory and analgesic activities, with no attempt to identify
      the active components. Chromatographic and spectroscopic procedures identified
      three new phytoecdysteroids: 21-hydroxyshidasterone (1), 11beta-hydroxy-20
      deoxyshidasterone (2), and 2,3-acetonide-24-hydroxyecdysone (3) from the stem
      bark methanol extracts along with known ecdysteroids shidasterone (4),
      ajugasterone C (5), 24-hydroxyecdysone (6), and 11beta,24-hydroxyecdysone (7).
      The compounds (1-7) showed significant (p <= 0.05) inhibitory effect at 100 mg/kg
      dose on rat paw oedema development due to carrageenan-induced inflammation in
      Sprague Dawley rats. These results suggest a possible contribution of
      ecdysteroids to the anti-inflammatory effect of some V. doniana stem bark
      extracts.

PMID- 23150079
TI  - How can ethics relate to science? The case of stem cell research.
AB  - We live in an era of an important turning point in the relationship between
      ethics (or, more accurately, bioethics) and science, notably due to both public
      interest and the gradual tightening of the gap in time between scientific
      discoveries and ethical reflection. The current bioethics debates of emerging
      situations (pluripotent stem cells, gene therapy, nanotechnology) have
      undoubtedly contributed to this change. Today, science happens and bioethics
      reflects on the possibilities, considers the risks, and advances proposals,
      which, without being scientific, can also imprint a mark on the path of
      scientific development. In this article, through the narrative of stem cell
      research, we will try to illustrate how bringing a bioethical viewpoint to the
      scientific debate can become a healthy exercise in both ethics and science,
      especially as narratives shift, as was the case in this field due to the
      introduction of induced pluripotent stem cells, the advent of which is not easily
      dissociated from the controversies related to embryo research. We should perhaps
      welcome this trend as promising for the future relationship between ethics and
      scientific research, providing a stimulus (and not a block) to the ever-evolving
      scientific discourse.

PMID- 23150080
TI  - The experience of 3 years of external quality assessment of preimplantation
      genetic diagnosis for cystic fibrosis.
AB  - Preimplantation genetic diagnosis (PGD) was first performed over 20 years ago and
      has become an accepted part of genetic testing and assisted reproduction
      worldwide. The techniques and protocols necessary to carry out genetic testing at
      the single-cell level can be difficult to master and have been developed
      independently by the laboratories worldwide offering preimplantation testing.
      These factors indicated the need for an external quality assessment (EQA) scheme
      for monogenic disease PGD. Toward this end, the European Society for Human
      Reproduction and Embryology came together with United Kingdom National External
      Quality Assessment Services for Molecular Genetics, to create a pilot EQA scheme
      followed by practical EQA schemes for all interested parties. Here, we detail the
      development of the pilot scheme as well as development and findings from the
      practical (clinical) schemes that have followed. Results were generally
      acceptable and there was marked improvement in results and laboratory scores for
      those labs that participated in multiple schemes. Data from the first three
      schemes indicate that the EQA scheme is working as planned and has helped
      laboratories improve their techniques and result reporting. The EQA scheme for
      monogenic PGD will continue to be developed to offer assessment for other
      monogenic disorders. 

PMID- 23150081
TI  - The next controversy in genetic testing: clinical data as trade secrets?
AB  - Sole-source business models for genetic testing can create private databases
      containing information vital to interpreting the clinical significance of human
      genetic variations. But incomplete access to those databases threatens to impede
      the clinical interpretation of genomic medicine. National health systems and
      insurers, regulators, researchers, providers and patients all have a strong
      interest in ensuring broad access to information about the clinical significance
      of variants discovered through genetic testing. They can create incentives for
      sharing data and interpretive algorithms in several ways, including: promoting
      voluntary sharing; requiring laboratories to share as a condition of payment for
      or regulatory approval of laboratory services; establishing - and compelling
      participation in - resources that capture the information needed to interpret the
      data independent of company policies; and paying for sharing and interpretation
      in addition to paying for the test itself. US policies have failed to address the
      data-sharing issue. The entry of new and established firms into the European
      genetic testing market presents an opportunity to correct this failure.

PMID- 23150087
TI  - Spring leaf phenology and the diurnal temperature range in a temperate maple
      forest.
AB  - Spring leaf phenology in temperate climates is intricately related to numerous
      aspects of the lower atmosphere [e.g., surface energy balance, carbon flux,
      humidity, the diurnal temperature range (DTR)]. To further develop and improve
      the accuracy of ecosystem and climate models, additional investigations of the
      specific nature of the relationships between spring leaf phenology and various
      ecosystem and climate processes are required in different environments. This
      study used visual observations of maple leaf phenology, below-canopy light
      intensities, and micrometeorological data collected during the spring seasons of
      2008, 2009, and 2010 to examine the potential influence of leaf phenology on a
      seasonal transition in the trend of the DTR. The timing of a reversal in the DTR
      trend occurred near the time when the leaves were unfolding and expanding. The
      results suggest that the spring decline in the DTR can be attributed primarily to
      the effect of canopy closure on daily maximum temperature. These findings improve
      our understanding of the relationship between leaf phenology and the diurnal
      temperature range in temperate maple forests during the spring. They also
      demonstrate the necessity of incorporating accurate phenological data into
      ecosystem and climate models and warrant a careful examination of the extent to
      which canopy phenology is currently incorporated into existing models. 

PMID- 23150086
TI  - Systemic treatment of gastrointestinal cancer in elderly patients.
AB  - PURPOSE: Gastrointestinal cancer (GI) incidence increases with each decade of
      life and is the leading cause of death in patients aged >70 years. Nevertheless,
      elderly patients are often excluded or underrepresented in clinical trials. We
      performed a review of current recommendations in the management of GI elderly
      cancer patients. METHODS: A comprehensive literature review was performed
      analyzing data about several meta-analysis and studies regarding chemotherapeutic
      regimens in elderly patients with colorectal and gastroesophageal cancers.
      RESULTS: Most of the studies demonstrated that the elderly experience the same
      advantages and toxicities from chemotherapy as younger individuals despite the
      fact that the data reviewed in this article provide evidence that elderly with GI
      cancers are underrepresented in clinical trials and few trials are conducted
      addressing the different risks and aims in older population. Each individual
      should be assessed for an appropriate regimen of treatment in the adjuvant or
      metastatic gastrointestinal cancer setting, and the decision of how to treat
      elderly must incorporate goals and preferences of the patient after a careful
      discussion of risks and benefits. CONCLUSION: Chronological age alone is not a
      sufficient factor to withhold curative/palliative treatment from an elderly GI
      cancer patient, and cofactors regarding their functional, social, and mental
      status have to be considered. For this purpose, several tools exist that may be
      utilized, such as geriatric assessment scores, comorbidity indices, frailty
      indices, scores for predicting toxicity from chemotherapy, and prognostic indices
      for survival.

PMID- 23150088
TI  - Climate change and thermal comfort in Hong Kong.
AB  - Thermal comfort is a major issue in cities and it is expected to change in the
      future due to the changing climate. The objective of this paper is to use the
      universal thermal comfort index (UTCI) to compare the outdoor thermal comfort in
      Hong Kong in the past (1971-2000) and the future (2046-2065 and 2081-2100). The
      future climate of Hong Kong was determined by the general circulation model (GCM)
      simulations of future climate scenarios (A1B and B1) established by the
      Intergovernmental Panel on Climate Change (IPCC). Three GCMs were chosen, GISS
      ER, GFDL-CM2.1 and MRI-CGCM2.3.2, based on their performance in simulating past
      climate. Through a statistical downscaling procedure, the future climatic
      variables were transferred to the local scale. The UTCI is calculated by four
      predicted climate variables: air temperature, wind speed, relative humidity and
      solar radiation. After a normalisation procedure, future UTCI profiles for the
      urban area of Hong Kong were created. Comparing the past UTCI (calculated by
      observation data) and future UTCI, all three GCMs predicted that the future
      climate scenarios have a higher mode and a higher maximum value. There is a shift
      from 'No Thermal Stress' toward 'Moderate Heat Stress' and 'Strong Heat Stress'
      during the period 2046-2065, becoming more severe for the later period (2081
      2100). Comparing the two scenarios, B1 exhibited similar projections in the two
      time periods whereas for A1B there was a significant difference, with both the
      mode and maximum increasing by 2 degrees C from 2046-2065 to 2081-2100.

PMID- 23150089
TI  - [Intermediate and high risk prostate cancer patients. Clinical significance of
      extended lymphadenectomy].
AB  - INTRODUCTION: We examined the quantity and localization of pelvic lymph node (LN)
      metastases in patients undergoing extended pelvic lymphadenectomy (ePLND).
      MATERIALS AND METHODS: A total of 174 patients with intermediate and high-risk
      prostate cancer underwent radical prostatectomy (RP) and ePLND. We analyzed the
      relationship between the number of LNs removed and the number, frequency and
      topography of LN metastases. RESULTS: In group 1 (intermediate risk patients,
      n=115) the average number of LNs removed was 20.5, LN metastases were found in 15
      patients (13 %) and the localizations were in the external iliac artery 19 %, the
      internal iliac artery 32 %, the  obturator foramen 36 %, the common iliac artery
      7 %, Marcille's triangle 3 % and sacral regions 3 %. In group 2 (high-risk
      patients, n=59) the average number of LNs removed was 23.9, LN metastases were
      found in 19 patients (32 %) and the localizations were the external iliac artery
      15 %, the internal iliac artery 26 %, the obturator foramen 19 %, the common
      iliac artery 29 %, Marcille's triangle 6 % and sacral regions 5 %. The full
      number of metastases was detected only if more than 15 LNs were removed in group
      1 and 18 LNs in group 2. CONCLUSIONS: At least 15 LNs in the intermediate risk
      group and at least 18 LNs in high risk group should be removed. The ePLND should
      include the common iliac artery, the internal iliac artery, Marcille's triangle
      and sacral regions.

PMID- 23150090
TI  - [Radiotherapy in the treatment of advanced and recurrent prostate cancer].
AB  - The incidence of advanced prostate cancer has decreased since the introduction of
      prostate-specific antigen (PSA) measurements. The treatment of these patients
      remains a challenge due to the bad prognosis and continues to be controversially
      discussed. The article discusses the questions concerning radiotherapy including
      pelvic lymph nodes as well as an additional androgen deprivation therapy. The
      risk of recurrent cancer has increased since the introduction of radical
      prostatectomy for patients with high risk factors or locally advanced tumors. In
      these cases adjuvant and salvage radiotherapy represent a mainstay of therapy.
      Low-dose rate (LDR) and high-dose rate (HDR) brachytherapy are primary treatment
      options for patients with low and high risk factors and localized disease. An
      elaborate management of treatment-related toxicities is mandatory and may provide
      persistent symptom relief. A comprehensive assessment of radiation side effects
      and treatment concepts is provided. The development of secondary cancers after
      radiotherapy represents a most severe side effect for which an assessment of
      available data is presented.

PMID- 23150092
TI  - Hepatitis C virus promotes T-helper (Th)17 responses through thymic stromal
      lymphopoietin production by infected hepatocytes.
AB  - Hepatitis C virus (HCV) is a major cause of liver cirrhosis and hepatocellular
      carcinoma. Here we report that infection of hepatic cells by HCV stimulates
      nuclear factor kappa B (NFkappaB)-dependent production of thymic stromal
      lymphopoietin (TSLP). Hepatocyte-derived TSLP in turn conditions dendritic cells
      (DCs) to drive T-helper (Th)17 differentiation. The TSLP secreted by HCV-infected
      hepatoma cells is capable of activating human monocyte-derived DCs by up
      regulating the expression of CD40, CD86, CCL17, CCL22, and CCL20 which are
      activating markers of DCs. In addition, the production of key cytokines for Th17
      differentiation, transforming growth factor beta (TGF-beta), interleukin (IL)-6,
      and IL-21, is enhanced by human monocytes upon coculture with HCV-infected cells.
      Importantly, the blockade of TSLP using neutralizing antibody prevented the
      activation and maturation of DCs as well as the production of Th17
      differentiation cytokines. DC conditioning by TSLP secreted from HCV-infected
      cells activated naive CD4+ T lymphocytes, resulting in Th17 differentiation.
      Furthermore, we can detect substantial levels of hepatocyte TSLP in fibrotic
      liver tissue from chronic HCV patients. Thus, blockade of TSLP released by HCV
      infected hepatocytes may suppress the induction/maintenance of hepatic Th17
      responses and halt the progression of chronic liver disease to fibrosis and liver
      failure. CONCLUSION: Hepatocyte-derived TSLP conditions DCs to drive Th17
      differentiation. Treatment of TSLP neutralizing antibody in HCV-infected
      hepatocyte/DC coculture abrogates DC conditioning and thereby inhibits Th17
      differentiation.

PMID- 23150093
TI  - Transmastoid galvanic stimulation does not affect the vergence-mediated gain
      increase of the human angular vestibulo-ocular reflex.
AB  - Vergence is one of several viewing contexts that require an increase in the
      angular vestibular-ocular reflex (aVOR) response. A previous monkey study found
      that the vergence-mediated gain (eye/head velocity) increase of the aVOR was
      attenuated by 64 % when anodic currents, which preferentially lower the activity
      of irregularly firing vestibular afferents, were delivered to both labyrinths. We
      sought to determine whether there was similar evidence implicating a role for
      irregular afferents in the vergence-mediated gain increase of the human aVOR. Our
      study is based upon analysis of the aVOR evoked by head rotations, delivered
      passively while subjects viewed a near (15 cm) or far (124 cm) target and
      applying galvanic vestibular stimulation (GVS) via surface electrodes. We tested
      12 subjects during 2-3 sessions each. Vestibular stimuli consisted of passive
      whole-body rotations (sinusoids from 0.05-3 Hz and 12-25 degrees /s, and
      transients with peak ~15 degrees , 50 degrees /s, 500 degrees /s(2)) and head-on
      body impulses (peak ~30 degrees , 150 degrees /s, 3,000 degrees /s(2)). GVS was
      on for 10 s every 20 s. All polarity combinations were tested, with emphasis on
      uni- and bi-lateral anodic inhibition. The average stimulus current was 5.9 +/-
      1.6 mA (range: 3-9.5 mA), vergence angle (during near viewing) was 22.6 +/- 2.8
      degrees  and slow-phase eye velocity caused by left anodic current stimulation
      with head stationary was -3.4 +/- 1.1 degrees /s, -0.2 +/- 0.6 degrees /s and 2.5
      +/- 1.4 degrees /s (torsion, vertical, horizontal). No statistically significant
      GVS effects were observed, suggesting that surface electrode GVS has no effect on
      the vergence-mediated gain increase of the aVOR at the current levels (~6 mA)
      tolerated by most humans. We conclude that clinically practical transmastoid GVS
      does not effectively silence irregular afferents and hypothesize that currents
      >10 mA are needed to reproduce the monkey results.

PMID- 23150094
TI  - Cochlear implantation via the middle fossa approach:  surgical and programming
      considerations.
AB  - OBJECTIVES: To report the results of cochlear implantation via the middle fossa
      approach in 4 patients, discuss the complications, and present a detailed
      description of the programming specifications in these cases. STUDY DESIGN:
      Retrospective case review. SETTING: Tertiary-care referral center with a well
      established cochlear implant program. PATIENTS: Four patients with bilateral
      canal wall down mastoid cavities who underwent the middle fossa approach for
      cochlear implantation. INTERVENTIONS: Cochlear implantation and subsequent
      rehabilitation. A middle fossa approach with cochleostomy was successfully
      performed on the most superficial part of the apical turn in 4 patients. A
      Nucleus 24 cochlear implant system was used in 3 patients and a MED-EL Sonata
      Medium device in 1 patient. The single electrode array was inserted through a
      cochleostomy from the cochlear apex and occupied the apical, middle, and basal
      turns. Telemetry and intraoperative impedance recordings were performed at the
      end of surgery. A CT scan of the temporal bones was performed to document
      electrode insertion for all of the patients. MAIN OUTCOME MEASURES:
      Complications, hearing thresholds, and speech perception outcomes were evaluated.
      RESULTS: Neural response telemetry showed present responses in all but 1 patient,
      who demonstrated facial nerve stimulation during the test. Open-set speech
      perception varied from 30% to 100%, despite the frequency allocation order of the
      MAP. CONCLUSION: Cochlear implantation via the middle cranial fossa is a safe
      approach, although it is a challenging procedure, even for experienced surgeons.

PMID- 23150095
TI  - Healing large traumatic eardrum perforations in humans using fibroblast growth
      factor applied directly or via gelfoam.
AB  - OBJECTIVE: The goal of this study was to evaluate the effects of conservative
      treatment and fibroblast growth factor (FGF) applied directly or via Gelfoam on
      the healing of large traumatic tympanic membrane perforations (TMPs) in humans.
      STUDY DESIGN: Prospective, randomized, controlled trial. METHODS: A randomized
      prospective analysis was performed between February 2009 and January 2011 for the
      treatment of traumatic TMPs in humans that affected greater than 50% of the TM.
      The closure rate, closure time, hearing gain, and rate of otorrhea were compared
      among the direct application of FGF, FGF via Gelfoam, and conservative treatment.
      RESULTS: A total of 94 patients were analyzed. The closure rates of large
      perforations in the direct FGF application, FGF via Gelfoam, and observation
      groups were 100%, 97%, and 55%, respectively. FGF-treated groups had
      significantly improved closure rates compared with the observation group (p <
      0.05). However, the closure rate did not differ significantly between patients
      who received FGF only and those who received FGF via Gelfoam (p > 0.05). FGF
      treated groups showed shorter mean closure times compared with the observation
      group (p < 0.05). However, the closure time did not differ significantly between
      FGF-treated groups (p > 0.05).All perforations were closed within 2 weeks,
      regardless of the presence of curled edges in the FGF-treated groups.

PMID- 23150096
TI  - Association of benign intracranial hypertension and spontaneous encephalocele
      with cerebrospinal fluid leak.
AB  - OBJECTIVE: To determine the incidence of intracranial hypertension in patients
      with spontaneous encephalocele with cerebrospinal fluid (CSF) leak. STUDY DESIGN:
      Retrospective case review. SETTING: Tertiary care neurotology practice. PATIENTS:
      Patients presenting between 2008 and 2011 with spontaneous encephalocele and CSF
      leak in the temporal bone. INTERVENTION(S): Lumbar puncture with opening pressure
      measurement after encephalocele repair. MAIN OUTCOME MEASURES: Patient age, sex,
      postoperative course, body mass index, and postoperative intracranial pressure.
      RESULTS: Of the 26 patients identified with spontaneous encephalocele with CSF
      leak, 9 patients had postoperative lumbar puncture data. Of those 9, 89% were
      female subjects, and 11% were male, with a mean age of 57 and a mean BMI of 41
      kg/m (morbidly obese). The mean opening pressure was 24.5 cm H(2)O. Approximately
      33% had normal intracranial pressure (mean, 15 cm H(2)O; range, 10-17 cm H(2)O);
      67% had elevated intracranial pressure (mean, 29 cm H(2)O; range, 23.5-40 cm
      H(2)O). The incidence of BIH in the general population is 0.001%. Of the 6 with
      intracranial hypertension, 3 (50%) were placed on acetazolamide for fundoscopic
      findings, postoperative headache, and/or visual changes. Mean time to LP after
      repair of encephalocele was 13 months (range, 4 days to 75 months). CONCLUSION:
      This study shows that benign intracranial hypertension is prevalent in a
      significant number of patients presenting with spontaneous encephalocele with CSF
      otorrhea at a rate much higher than is found in the general population. This
      finding has direct clinical implications and suggests that all patients with
      spontaneous encephalocele/CSF leak warrant evaluation for benign intracranial
      hypertension.

PMID- 23150097
TI  - Effect of cochlear window fixation on air- and bone-conduction thresholds.
AB  - HYPOTHESIS: In the absence of patent cochlear windows, cochlear fluid inertia
      depends on the presence of a "third window" as a major component of the bone
      conduction response. BACKGROUND: Studies have shown conflicting results regarding
      changes in air and bone conduction whenever, the round window, oval window, or
      both windows were occluded. METHOD: The study was performed in a tertiary
      university-affiliated medical center. Auditory brain responses to clicks and 1
      kHz tone bursts delivered by air and bone conduction were tested in 5 adult-size
      fat sand rats. The round window membrane (total, 7 ears) was sealed with Super
      Glue, and auditory brain response testing was repeated. Thereafter, the stapes
      footplate was firmly fixated, and auditory brain responses were recorded for a
      third time. RESULTS: Round-window fixation induced a significant increase in air
      conduction thresholds to clicks from 36.4 +/- 0.9 to 69.3 +/- 4.1 dB SPL, with no
      significant change in bone-conduction thresholds. When the stapes footplate was
      immobilized as well, air conduction increased by another 20 dB, on average, with
      no change in bone conduction. A similar deterioration was seen in response to 1
      kHz stimulus. CONCLUSION: These findings support and complement earlier studies
      in the same animal model, suggesting that when the pressure outlet through the
      cochlear windows are abolished, still bone conduction displaces the cochlear
      partition probably because of a functioning "third window."

PMID- 23150098
TI  - Cold-adapted arsenite oxidase from a psychrotolerant Polaromonas species.
AB  - Polaromonas sp. str. GM1 is an aerobic, psychrotolerant, heterotrophic member of
      the Betaproteobacteria and is the only isolate capable of oxidising arsenite at
      temperatures below 10  degrees C. Sequencing of the aio gene cluster in GM1
      revealed the presence of the aioB and aioA genes, which encode the arsenite
      oxidase but the regulatory genes typically found upstream of aioB in other
      members of the Proteobacteria were absent. The GM1 Aio was purified to
      homogeneity and was found to be a heterodimer. The enzyme contained Mo and Fe as
      cofactors and had, using the artificial electron acceptor 2,6
      dichlorophenolindophenol, a Km for arsenite of 111.70 +/- 0.88 MUM and a Vmax of
      12.16 +/- 0.30 U mg(-1), which is the highest reported specific activity for any
      known Aio. The temperature-activity profiles of the arsenite oxidases from GM1
      and the mesophilic betaproteobacterium Alcaligenes faecalis were compared and
      showed that the GM1 Aio was more active at low temperatures than that of A.
      faecalis. A homology model of the GM1 Aio was made using the X-ray crystal
      structure of the Aio from A. faecalis as the template. Structural changes that
      account for cold adaptation were identified and it was found that these resulted
      in increased enzyme flexibility and a reduction in the hydrophobicity of the
      core.

PMID- 23150099
TI  - Risk of premature ovarian failure is associated to the PvuII polymorphism at
      estrogen receptor gene ESR1.
AB  - PURPOSE: Estrogen plays an important role in the human reproductive system and it
      action is mediated mainly by two specific receptors: alpha (ERalpha) and beta
      (ERbeta). There were described polymorphic variants in ESR1 and ESR2 genes and
      studies showed controversial results regarding their association with premature
      ovarian failure. We aimed to determine the prevalence of ESR1 and ESR2
      polymorphisms in Brazilian patients and controls. After associate the
      polymorphisms with premature ovarian failure (POF). METHODS: Genetic association
      study was performed with 70 women with POF and 73 normally menopaused controls.
      Detection of ESR1 (PvuII/and XbaI) and ESR2 (AluI and RsaI) gene polymorphisms
      were performed using TaqMan PCR. The single-nucleotide polymorphism (SNPs) and
      haplotype effects were analyzed by multivariate logistic regression and haplotype
      analysis and a p-value < 0.05 was considered significant. RESULTS: Individual SNP
      analysis revealed that PvuII polymorphism was statistically associated with POF
      (p = 0.034) under a recessive model. Regarding XbaI, AluI and RsaI SNPs, no
      statistical difference was observed between POF group and controls (p = 0.575, p
      = 0.258 and p = 0.483, respectively). Combined genotypes of ESR1 and ESR2
      polymorphisms did not identify a risk haplotype associated with POF. CONCLUSION:
      In Brazilian population evaluated results have demonstrated that the genetic
      variation in ESR1 gene (PvuII polymorphism) is associated to POF risk.

PMID- 23150100
TI  - Predicting enzymatic function from global binding site descriptors.
AB  - Due to the rising number of solved protein structures, computer-based techniques
      for automatic protein functional annotation and classification into families are
      of high scientific interest. DoGSiteScorer automatically calculates global
      descriptors for self-predicted pockets based on the 3D structure of a protein.
      Protein function predictors on three levels with increasing granularity are built
      by use of a support vector machine (SVM), based on descriptors of 26632 pockets
      from enzymes with known structure and enzyme classification. The SVM models
      represent a generalization of the available descriptor space for each enzyme
      class, subclass, and substrate-specific sub-subclass. Cross-validation studies
      show accuracies of 68.2% for predicting the correct main class and accuracies
      between 62.8% and 80.9% for the six subclasses. Substrate-specific recall rates
      for a kinase subset are 53.8%. Furthermore, application studies show the ability
      of the method for predicting the function of unknown proteins and gaining
      valuable information for the function prediction field.

PMID- 23150101
TI  - The Validity of Implicit Association Test (IAT) measures of sexual attraction to
      children: a meta-analysis.
AB  - The current study presents a quantitative review of the discriminative and
      convergent validity of Implicit Association Test (IAT) measures adapted to assess
      sexual interest in children. IAT measures were able to distinguish sex offenders
      against children (SOC) from non-SOC (M weighted d from random-effects = 0.63, 95
      % CI [0.42-0.83], N = 707, k = 12). The largest group differences were found
      between SOC and non-offenders, followed by non-sex offenders and rapists. IAT
      measures using sex versus not sex (and similar attribute categories, such as sex
      vs. neutral) provided superior discrimination compared to IAT measures using sexy
      versus not sexy (and similar attribute categories, such as erotic vs. non
      erotic). The IAT measures had a moderate relationship to self-report (r = .27, 95
      % CI [.13-.40], N = 182), sexual offense history variables (r = .27, 95 % CI [.08
      .43], N = 145), and viewing time (r = .30, 95 % CI [.16-.43], N = 180) measures
      of sexual interest in children. Although these IAT measures can discriminate
      between groups and show convergence with other measures of sexual interest, a
      better understanding of the construct validity of these tools is required before
      their use in the assessment, treatment, and supervision of sex offenders.

PMID- 23150102
TI  - Adults' attitudes about gender nonconformity in childhood.
AB  - This study examined attitudes about outcomes associated with childhood gender
      nonconformity. Participants were 518 undergraduate students (337 female; 181
      male) at a midwestern university in the U.S. Participants were presented with 1
      of 10 vignettes describing a target child (male or female) who varied in gendered
      traits, interests, and behaviors (strongly masculine, moderately masculine,
      neutral, moderately feminine or strongly feminine). They completed a 50-item
      questionnaire including demographics, predicted outcomes for the target (e.g.,
      masculinity and femininity in adulthood, pressure to change, psychological
      adjustment in childhood and adulthood, and sexual orientation), and the Attitudes
      toward Women Scale (Spence et al., 1973). Participants thought masculine and
      feminine targets would be masculine and feminine in adulthood, respectively:
      thus, stability was expected for both sexes. Feminine targets, boys or girls,
      were thought to be more likely to display internalizing (e.g., anxiety,
      depression) behaviors and masculine targets more likely to display externalizing
      (e.g., aggression, conduct disorders) behaviors in both childhood and adulthood.
      Gender-nonconforming children were expected to experience more pressure to change
      their behavior and less likely to be exclusively heterosexual adults, the latter
      particularly so for strongly feminine boys. There were few significant effects of
      participant sex and no effects of attitudes about gender on any of these
      measures. These findings add to the literature by demonstrating that degrees of
      masculinity and femininity as well as of gender nonconformity are expected to be
      associated with predictable outcomes in a linear fashion in both sexes, with only
      a few differences between expectations for boys and girls.

PMID- 23150104
TI  - Should a psychiatrist give legal advice on cosmetic genital surgery?

PMID- 23150103
TI  - The development of conventional sexual partner trajectories among african
      american male adolescents.
AB  - African American male youth disproportionately report involvement with multiple
      sexual partners, which increases their risk for sexually transmitted infections
      and initiation of unplanned pregnancies. Little is known about the developmental
      precursors of sexual partner trajectories among African American male youth.
      Moreover, few studies focus on the many African American youth who evince highly
      conventional sexual partner trajectories, i.e., youth who have only one partner
      or abstain from sexual activity across time. Using four waves of data from a
      longitudinal study, we hypothesized that an accumulation of social and economic
      disadvantages in early adolescence would negatively influence youths'
      conventional sexual partner trajectories in late adolescence. We expected these
      disadvantages to affect youths' receipt of protective family processes and their
      reports of a set of intrapersonal processes (self-regulation, hope, and low
      levels of anger) linked to generally conventional behavior. Hypotheses were
      tested with data from 315 African American male youth from 11 to 18.5 years of
      age and their primary caregivers. Our results supported the hypotheses.
      Socioeconomic disadvantages during preadolescence predicted less involvement in
      conventional sexual partner trajectories from ages 16 to 18.5 years. This
      association was mediated by protective family processes and a set of interrelated
      intrapersonal protective processes. Preventive interventions designed to promote
      protective parenting and intrapersonal processes can be expected to promote
      sexual behavior trajectories characterized by abstinence or relations with very
      few partners. 

PMID- 23150105
TI  - Palliative care for all?

PMID- 23150106
TI  - [Frequency of cardiac arrhythmia in patients with liver cirrhoses and evaluation
      of associated factors].
AB  - INTRODUCTION: Studies analysing the frequency of rhythm disorders in patients
      with cirrhosis are rare. Nevertheless, factors triggering rhythm disorders occur
      frequently in cirrhosis. Therefore, a retrospective case control study was
      performed investigating the frequency of cardiac arrhythmia in a population of
      patients with cirrhosis while evaluating several associated factors. METHODS: The
      files of patients with cirrhosis (n  =  293) in the period 2004 - 2008 were
      analysed retrospectively regarding cardiac arrhythmia. The frequency of cardiac
      arrhythmia in the presence of relevant risk factors was analysed using chi 2tests
      and logistic regression models. RESULTS: 61.1  % of all patients were male (mean
      age 61.7 years) and 38.9  % female (mean age 62.8 years). The severity of
      cirrhosis according to the Child-Pugh score (CP) was as follows: CP A 43.3  %, CP
      B 32.8  % and CP C 23.9  %. Altogether, rhythm disorders were diagnosed in 16.4 
      % (48/293) of the study population, most frequently atrial fibrillation (68.8  %)
      and atrial flutter (6.7  %). An advanced age and comorbidities such as
      arteriosclerotic diseases, hypercholesterinemia (p  <  0.001, each) and diabetes
      mellitus (p  =  0.013) correlated significantly with the frequency of rhythm
      disorders which occurred more often in males than in females (p  = 0.066).
      Ongoing alcohol abuse, the severity of cirrhosis and arterial hypertension were
      not associated significantly with the onset of rhythm disorders. 84.4  % of all
      patients with cardiac arrhythmia were treated by diuretics. Decreased (<  3.5
      mmol/L) and elevated (>  5 mmol/L) potassium values were observed in 60.6  % of
      the study collective. Rhythm disorders were more often observed in patients with
      hyperkalemia (especially atrioventricular block, p  < 0.01). CONCLUSION: Compared
      to the average population, the prevalence of atrial fibrillation was increased in
      our cirrhotic cohort. The occurrence of rhythm disorders was significantly
      associated with arteriosclerotic diseases, hypercholesterinaemia and diabetes
      mellitus. Additionally, cardiac arrhythmia must be considered under diuretic
      therapy and in the presence of electrolyte disturbances.

PMID- 23150107
TI  - [Current clinical practice among German Internists regarding the prophylaxis of
      gastroduodenal ulcers associated with NSAIDs, aspirin and Helicobacter pylori].
AB  - OBJECTIVE: Rapidly growing information on adverse gastrointestinal effects of non
      steroidal anti-inflammatory drugs (NSAIDs) and Helicobacter pylori (Hp) causes
      continuous changes in clinical patient management. Decisions on the prevention of
      gastroduodenal ulcers in individual patients often do not follow guidelines. We
      aimed to assess the current management of gastroduodenal ulcers by internists in
      southern Germany. METHODS: All 965 members of the Association of Bavarian
      Internists, a German province with about 8000 internists, were invited to
      participate in answering a 12-item questionnaire. The questions addressed
      different clinical scenarios regarding ulcer disease associated with traditional
      NSAIDs (tNSAIDs), aspirin and Hp. Particularly, we asked for the clinical
      approach to patients with NSAID-/aspirin-associated ulcers and prophylactic
      measures before the beginning of a potentially ulcerogenic medication. RESULTS: N
      = 225 (23.3 %) physicians returned completed questionnaires. In patients with Hp
      negative, NSAID-/aspirin-associated ulcers, > 80 % of respondents would initiate
      long-term proton pump inhibitor (PPI) therapy, whereas 20 % and 17.8 % would
      prescribe COX-2 selective inhibitors or opiates instead of non-selective NSAIDs
      and clopidogrel instead of aspirin. The management of Hp-positive ulcers,
      especially in cases with additional use of aspirin or NSAIDs, was very
      heterogenous, including Hp-eradication only, eradication +  long-term PPI,
      eradication +  clopidogrel or COX-2-inhibitors/opiates. CONCLUSION: This survey
      depicts individual discrepancies in the clinical management of patients receiving
      NSAIDs and/or aspirin, regarding the prophylaxis of gastroduodenal ulcer disease.

PMID- 23150108
TI  - An unusual case of paralytic ileus.
AB  - A 26-year-old female patient presented with the clinical picture of an acute
      ileus. Since childhood the patient has been diagnosed as having a MELAS syndrome,
      a mitochondriopathy. A subtotal colectomy was performed some years ago because of
      a similar ileus episode. The further diagnostic work-up revealed an expanded
      small intestine in abdominal radiography. Laboratory analysis showed increased
      levels of serum lactate with a consecutive respiratory compensated metabolic
      acidosis. A conservative treatment regime with nasogastric tube, fluid therapy,
      parental nutrition via peripheral veins and peristalsis inducing drugs was
      initiated, but did not resolve ileus symptoms. Under the hypothesis that in MELAS
      syndrome the ileus-related catabolic state aggravates the ileus symptoms in terms
      of a circulus vitiosus, we started high-caloric parenteral nutrition by using a
      central venous catheter. A few hours after this intervention, a clear clinical
      improvement could be observed. Since this initial presentation, the patient was
      admitted to our hospital several times with the same ileus symptoms. Each of the
      episodes was successfully and rapidly treated by this high-caloric parenteral
      nutrition therapy. The reproducible rapid clinical improvement after starting
      parenteral nutrition supports the hypothesis that an optimal energy supply is the
      key therapy not only for cerebral but also for gastrointestinal symptoms in
      patients with MELAS syndrome.

PMID- 23150109
TI  - [Phytobezoar in the common hepatic duct - rare cause of obstructive jaundice
      following pancreatoduodenectomy: case report and review of the literature].
AB  - Obstruction of bile flow following pancreatoduodenectomy can be caused by
      stenosis of the hepaticojejunostomy created at the time of surgery, obstruction
      of the bile-draining jejunal loop, stones or, very rarely, ingested foreign
      bodies in the common hepatic duct. In analogy with endoscopic sphincterotomy or
      the once popular side-to-side-choledochduodenostomy, the creation of a
      hepaticojejunostomy eliminates the barrier of the sphincter Oddi, enabling
      intestinal content such as ingested foreign bodies or food fibers to migrate into
      the bile duct. We report on the case of a patient developing biliary tract
      obstruction due to fibrous material in the common hepatic duct 15 years after
      pancreatoduodenectomy. In addition, an overview of the literature on the rare
      phenomenon of foreign body-associated obstructive jaundice is given.

PMID- 23150110
TI  - [Human beta-defensin 1: from defence to offence].
AB  - The human gut is colonised by about one kilogram of commensal bacteria. These
      microorganisms are a potential threat, thus an efficient defence system is
      crucial in preventing bacterial translocation and infection. Besides other
      mechanisms of protection humans produce antimicrobial peptides (AMPs) that are
      able to kill a broad range of microorganisms. The human beta-defensin 1 (hBD-1)
      plays a major role because it is produced constitutively by all human epithelia
      and some immune cells. In contrast to other AMPs, however, the biological
      function of hBD-1 has remained unclear since the antibiotic activity of hBD-1 in
      vitro was only marginal. But still, several diseases have been associated with
      genetic polymorphisms in the hBD-1 encoding gene. Herein we discuss why the
      biological role of hBD-1 has been overlooked and how hBD-1 can be activated by
      chemical reduction. We elaborate on the biological significance of this
      activation and its importance for inflammatory bowel disease.

PMID- 23150113
TI  - [In Memoriam. Obituary: Max Michel Forell].

PMID- 23150111
TI  - [S3-Consensus guidelines on definition, etiology, diagnosis and medical,
      endoscopic and surgical management of chronic pancreatitis German Society of
      Digestive and Metabolic Diseases (DGVS)].

PMID- 23150112
TI  - [Method report to the S3 guideline chronic pancreatitis: definition, etiology,
      diagnostics and conservative, interventional endoscopic and surgical therapy of
      the chronic pancreatitis].

PMID- 23150114
TI  - Associations between EEG beta power abnormality and diagnosis in cognitive
      impairment post cerebral infarcts.
AB  - Cerebral infarct is a common disease of older adults, which could increase the
      risk for cognitive impairment and dementia. Electroencephalogram (EEG)
      characteristics were analyzed to investigate the applied value in the assessment
      of cognitive impairment of the cerebral infarct patients. One hundred ten
      subjects with cerebral infarcts (including 65 cases of cognitive impairment
      patients (CI-CI) and 45 cases of cognitive normality patients (CI-NC)) and 110
      normal health persons (NC) were recruited between July 2009 and March 2011 at the
      Department of Neurology. All of the patients were analyzed by EEG within 1 day
      they were hospitalized. The EEG analysis results were compared with the Montreal
      Cognitive Assessment (MoCA) scale (assessed within 2 weeks) with the methods of
      correlation analysis, clustering analysis, and concordance analysis. The results
      indicated that CI-CI patients had significantly lower EEG beta power (0.832 +/-
      0.203 mcV(2)) relative to the CI-NC group (1.493 +/- 0.271 mcV(2), P < 0.01) or
      NC group (1.565 +/- 0.345 mcV(2), P < 0.01). Significant negative correlation
      between the beta power and infarct size (as well as infarct number) was
      discovered (r = -0.88881 and -0.66498, respectively, both P < 0.001). There was a
      good concordance between K-means clustering algorithm calculating the beta power
      and MoCA scoring (Kappa = 0.851, P < 0.001). The preliminary findings suggest
      that the recognition techniques of EEG hold considerable promise for the
      assessment of cognitive impairment post cerebral infarcts within 2 weeks and
      which related to the size of infarcts and number of infarcts.

PMID- 23150116
TI  - Ursodeoxycholic acid and its emerging role in attenuation of tumor growth in
      gastrointestinal malignancies.

PMID- 23150117
TI  - Bile acids for cachexia therapy : Reply to the letter by Shailendra Kapoor:
      Ursodeoxycholic acid and its emerging role in attenuation of tumor growth in
      gastrointestinal malignancies.

PMID- 23150115
TI  - Genotyping of skin and soft tissue infection (SSTI)-associated methicillin
      resistant Staphylococcus aureus (MRSA) strains among outpatients in a teaching
      hospital in Japan: application of a phage-open reading frame typing (POT) kit.
AB  - We aimed to elucidate the current epidemiological features of outpatient skin and
      soft tissue infection (SSTI)-associated methicillin-resistant Staphylococcus
      aureus (MRSA) in Japan. Altogether, we evaluated the performance of a phage-open
      reading frame typing (POT) kit for genotyping these MRSA strains. We collected 57
      MRSA strains from all outpatients with SSTIs attending a teaching hospital in
      Japan. Drug susceptibility measurement and genotyping including SCCmec typing,
      spa typing, multilocus sequence typing, pulsed-field gel electrophoresis, and
      commercial POT-kit were performed. The majority of strains (39 strains, 68 %) had
      the SCCmec-II element. Seventeen strains (30 %) with SCCmec-IV accounted for the
      second largest population. Strains with SCCmec-IV and SCCmec-V appeared
      multiclonal, and a predominance of Panton-Valentine leukocidin (PVL) gene
      negative CC8/spa-CC008 strains, as well as the first isolate of an ST93 strain in
      Japan, was observed among them. Only one USA300 strain was identified. Strains
      with SCCmec-IV and SCCmec-V were significantly susceptible to antimicrobials. The
      PVL gene was found in 5 SCCmec-IV strains and 1 SCCmec-V strain. The POT-kit
      successfully predicted the SCCmec type in 54 strains (95 %), and typing by POT1
      scores was highly concordant with SCCmec typing and spa typing. Moreover, three
      PVL-positive strains fell into a particular POT type (POT scores, 106-77-113).
      Simpson's index of the POT-kit was 0.977. In conclusion, the present study
      clarified the multiclonal nature of outpatient SSTI-associated MRSA in a teaching
      hospital in Japan. These data also underscore the utility of the POT-kit for non
      outbreak surveillance through its simple platform consisting of two multiplex
      PCRs without sequencing.

PMID- 23150118
TI  - Patient dose during carotid artery stenting with embolic-protection devices:
      evaluation with radiochromic films and related diagnostic reference levels
      according to factors influencing the procedure.
AB  - PURPOSE: To measure the maximum entrance skin dose (MESD) on patients undergoing
      carotid artery stenting (CAS) using embolic-protection devices, to analyze the
      dependence of dose and exposure parameters on anatomical, clinical, and technical
      factors affecting the procedure complexity, to obtain some local diagnostic
      reference levels (DRLs), and to evaluate whether overcoming DRLs is related to
      procedure complexity. MATERIALS AND METHODS: MESD were evaluated with
      radiochromic films in 31 patients (mean age 72 +/- 7 years). Five of 33 (15 %)
      procedures used proximal EPD, and 28 of 33 (85 %) procedures used distal EPD.
      Local DRLs were derived from the recorded exposure parameters in 93 patients (65
      men and 28 women, mean age 73 +/- 9 years) undergoing 96 CAS with proximal (33 %)
      or distal (67 %) EPD. Four bilateral lesions were included. RESULTS: MESD values
      (mean 0.96 +/- 0.42 Gy) were <2 Gy without relevant dependence on procedure
      complexity. Local DRL values for kerma area product (KAP), fluoroscopy time (FT),
      and number of frames (NFR) were 269 Gy cm(2), 28 minutes, and 251, respectively.
      Only simultaneous bilateral treatment was associated with KAP (odds ratio [OR]
      10.14, 95 % confidence interval [CI] 1-102.7, p < 0.05) and NFR overexposures (OR
      10.8, 95 % CI 1.1-109.5, p < 0.05). Type I aortic arch decreased the risk of FT
      overexposure (OR 0.4, 95 % CI 0.1-0.9, p = 0.042), and stenosis >= 90 % increased
      the risk of NFR overexposure (OR 2.8, 95 % CI 1.1-7.4, p = 0.040). At
      multivariable analysis, stenosis >= 90 % (OR 2.8, 95 % CI 1.1-7.4, p = 0.040) and
      bilateral treatment (OR 10.8, 95 % CI 1.1-109.5, p = 0.027) were associated with
      overexposure for two or more parameters. CONCLUSION: Skin doses are not
      problematic in CAS with EPD because these procedures rarely lead to doses >2 Gy.

PMID- 23150119
TI  - Quality improvement guidelines for transcatheter embolization for acute
      gastrointestinal nonvariceal hemorrhage.

PMID- 23150120
TI  - Hemophilic chronic synovitis: therapy of hemarthrosis using endovascular
      embolization of knee and elbow arteries.
AB  - PURPOSE: Congenital hemophilia is a hereditary bleeding disorder that affects 1
      in 5,000 males and is characterized by repetitive musculoskeletal bleeding
      episodes. Selective embolization of the knee and elbow arteries can prevent
      bleeding episodes. To evaluate the long-term efficacy of these procedures, we
      assessed the outcomes of 30 procedures performed in our center. METHODS: We
      performed 30 procedures in 27 hemophilic patients, including 23 knee, and 7 elbow
      procedures. To evaluate the efficacy of selective embolization of knee and elbow
      arteries in people with hemophilia, we analyzed the number of bleeding episodes
      during 12 months before the procedure compared with the amount of episodes that
      occurred 3, 6, and 12 months after embolization. RESULTS: Twenty-nine of 30
      procedures were classified as successful. The median of 1.25 episodes per month
      (range 0-3) observed before the procedure was reduced to 0 (range 0-1.67; p <
      0.001) at 3 months, 0.17 (range 0-1.67; p < 0.001) at 6 months, and 0.33 (range 0
      1.67; p = 0.024) at 12 months. Three patients remained free of bleeding events
      for more than 6 months. Additionally, after the procedure there was a significant
      reduction in factor FVIII usage that sustained up to 12 months after the
      procedures. No serious adverse events were observed. CONCLUSIONS: Selective
      angiographic embolization of knee and elbow arteries is a feasible procedure that
      can prevent repetitive bleedings, which would translate in better joint outcomes
      for these patients.

PMID- 23150121
TI  - The use of biodegradable stents in malignant oesophageal strictures for the
      treatment of dysphagia before neoadjuvant treatment or radical radiotherapy: a
      feasibility study.
AB  - PURPOSE: To evaluate the clinical results of the use of biodegradable oesophageal
      stents in malignant strictures. METHODS: Eleven patients were included in this
      prospective analysis in which a woven polydioxanone biodegradable oesophageal
      stent was used. The inclusion criterion was that the patient underwent
      neoadjuvant treatment or radical radiotherapy after the stent insertion. Primary
      end points were dysphagia score at discharge, stent patency, and complication
      rate. Secondary end points were overall survival and surgical outcome of surgery.
      RESULTS: There was a 100% procedure technical success rate. Early complications
      occurred in three patients resulting in failure to restore oral nutrition. In the
      remaining eight patients, dysphagia was significantly improved at discharge. Mean
      stent patency rate in this group was 71.5 days. Stent dysfunction occurred in
      five of eight patients (62.5%); in two of five patients this was due to local
      inflammatory reaction, and in three of five patients it was due to tumour growth
      after a mean time of 97.8 days, and a new metallic stent was consequently placed
      in four of five patients. One patient was successfully treated with
      esophagectomy. At the end of follow-up (mean time 102.1 days), three of eight
      stents were patent. The overall patient survival rate was 81.8%. CONCLUSION:
      Although short-term dysphagia scores improved, biodegradable stents do not appear
      to offer a clear beneficial effect in most cases of malignant strictures,
      particularly due to a local inflammatory reaction that may be induced. Technical
      improvement of the device and delineation of the patient group that would benefit
      from its use is necessary if further studies are to be conducted in the future.

PMID- 23150122
TI  - Diagnosis and management of puerperal hematomas: two cases.

PMID- 23150123
TI  - Rare anomalous origin of superior left pulmonary artery from left subclavian
      vein.
AB  - We report for the first time an extremely rare anomalous origin of the superior
      left pulmonary artery in a 60 year-old man. Although it was occult in clinical
      indications, such a malformation still ought to be considered, especially during
      endovascular procedures.

PMID- 23150124
TI  - Gold(I)-catalyzed divergence in the preparation of bicyclic enol esters: from
      exclusively [3C+2C]-cycloaddition reactions to exclusive formation of
      vinylcyclopropanes.
AB  - With the use of benzonitrile-stabilized Au(I) catalyst [Au(IPr)(NCPh)]SbF(6) (Ic;
      IPr=1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene), a spectrum of reactivity
      is observed for propargyl ester 4a with cyclic vinyl ethers, ranging from
      exclusively [3C+2C] cycloaddition reactions to exclusively cyclopropanation
      depending only on the structure of the substrate. Some initially formed
      cyclopropanation products rearrange into the corresponding formally [3C+2C]
      cycloaddition products after treatment with fresh Au(I) complex at 80  degrees C.
      Vinylcyclopropanes formed from dihydrofuran and dihydropyran resisted such
      rearrangement, even in the presence of fresh Au(I) catalyst at elevated
      temperature. This study addresses an important mechanistic question concerning
      whether the five-membered-ring products were produced by a direct [3C+2C]
      cycloaddition reaction or by a sequential cyclopropanation/ring-expansion
      reaction. A dual pathway is proposed for the Au(I)-catalyzed reactions between
      propargyl esters and cyclic vinyl ethers. The different behavior among vinyl
      cyclic ethers is attributed to the difference in the polarization of the pi bond.
      Highly polarized bonds appear to undergo the cycloaddition reaction whereas less
      polar pi-bonds produce cyclopropanes.

PMID- 23150125
TI  - High antioxidant activity mixture of extruded whole quality protein maize and
      common bean flours for production of a nutraceutical beverage elaborated with a
      traditional Mexican formulation.
AB  - The objective of this study was to determine the best combination of extrusion
      process variables for the production of whole quality protein maize (EQPMF) and
      common bean (ECBF) flours to prepare a high antioxidant activity mixture (EQPMF +
      ECBF) suitable to produce a nutraceutical beverage with high acceptability
      elaborated with a traditional Mexican formulation. Processing conditions were
      obtained from a factorial combination of barrel temperature (BT = 120-170 
      degrees C) and screw speed (SS = 120-200 rpm). Response surface methodology was
      applied to obtain maximum values for antioxidant activity (A ( ox ) A) of the
      flour mixture (EQPMF + ECBF) and acceptability (A) of the nutraceutical beverage.
      The best combinations of extrusion process variables for EQPMF and ECBF to
      prepare an optimized mixture (60%EQPMF + 40%ECBF) were BT = 98  degrees C/SS =
      218 rpm and BT = 105  degrees C/SS = 83 rpm, respectively. The optimized mixture
      had A ( ox ) A = 14,320 MUmol Trolox equivalent (TE)/100 g sample dry weight (dw)
      and a calculated protein efficiency ratio (C-PER) of 2.17. A 200 ml portion of a
      beverage prepared with 25 g of the optimized flour mixture had A ( ox ) A = 3,222
      MUmol TE, and A = 89 (level of satisfaction "I like it extremely"). This
      nutraceutical beverage could be used as an alternative to beverages with low
      nutritional/nutraceutical value, such as those prepared with water, simple
      sugars, artificial flavoring and colorants, which are widely offered in the
      market.

PMID- 23150127
TI  - [Patient safety in clinical medicine].

PMID- 23150126
TI  - Influence of red pepper spice and turmeric on inflammation and oxidative stress
      biomarkers in overweight females: a metabolomics approach.
AB  - Red pepper spice (RP) and turmeric (TM) are used as flavorings in foods and for
      medicinal purposes. Utilizing a randomized, doubled-blinded, placebo-controlled,
      crossover design (2-week washout), 4-week supplementation with RP (1 g/d) or TM
      (2.8 g/d) was tested for influences on inflammation and oxidative stress in 62
      overweight/obese (body mass index >= 27 kg/m2) females (40-75 years) with
      systemic inflammation (C-reactive protein, CRP >= 2 mg/l). Overnight, fasted
      blood samples were collected pre- and post-supplementation, and analyzed for
      oxidative stress (F2-isoprostanes, oxidized low density lipoprotein),
      inflammation (CRP and seven inflammatory cytokines), and metabolic profiles using
      gas chromatography-mass spectrometry with multivariate partial least square
      discriminant analysis (PLS-DA). Pre- to post-supplementation measures of
      inflammation and oxidative stress for both RP and TM did not differ when compared
      to placebo (all interaction effects, P > 0.05), and global metabolic difference
      scores calculated through PLS-DA were non-significant (both spices, Q2Y < 0.40).
      These data indicate that 4-week supplementation with RP or TM at culinary levels
      does not alter oxidative stress or inflammation in overweight/obese females with
      systemic inflammation, or cause a significant shift in the global metabolic
      profile.

PMID- 23150128
TI  - [Cases from the expert commission of the North Rhine medical council: expert
      commissions and arbitration boards by medical councils].
AB  - Following a description of the structure and function of the expert commission
      for medical malpractice of the North Rhine medical council, important legal
      technical terms and the consequences, such as the definition of accusable medical
      malpractice and severe (in legal terms gross) negligence will be presented. The
      article reports on the legal consequences of the lack of informed consent, on the
      significance of insufficient informed consent and under which conditions a
      transfer of liability becomes valid. From the statistical information in the
      archives of the expert commission it can be seen that in processes against
      urologists approximately 31% of urologists in private practice were affected
      compared to 69% of hospital urologists. Approximately 20% involved accusations of
      false diagnosis and 80% involved accusations of false treatment. Of the processes
      involving urological diagnostic errors prostate cancer was at the forefront,
      followed by processes involving delayed or falsely diagnosed bladder cancer. For
      processes due to operative treatment errors prostate cancer also occupied first
      place, followed by accusations of treatment errors involving penile and urethral
      operations. A differentiated presentation of processes involving non-operative
      treatment errors revealed an accumulation of accusations for mistakes in the
      treatment of urolithiasis, in medicinal treatment and also in tumor therapy.
      Following a description of typical individual cases, indications for avoidance of
      legal proceedings will be given.

PMID- 23150129
TI  - [Patient safety: data on the topic and ways out of the crisis].
AB  - Studies have shown for many years that the cause of errors or patient injury is
      in a high proportion of cases to be found under human factors. Human factors
      include all those factors which determine the safety and capabilities of humans
      especially in complex situations or systems. Up to now this topic has barely been
      systematically dealt with in training and there is a large deficit. Modern
      simulation team training with systematic use of established principles of adult
      education and the implementation of crisis resource management (CRM) for teams
      can have enormous positive effects for patient safety. The concept of CRM for
      increasing human reliability is, however, barely used systematically for
      training. Simulation team training for critical events (not for emergency cases)
      is barely used. Professional performance at the highest level can only be
      expected from teams which regularly participate in team training for critical
      situations. In addition to simulation training with human factors, other aspects
      of patient safety are also essential. The concept of high reliability
      organizations (HRO) could make an important contribution in the sense of a safe
      hospital concept and includes the collection and analysis of critical incidents
      (critical incident reporting system CIRS) as well as the focus on the system of
      patient safety instead of individual persons and errors.

PMID- 23150130
TI  - [Learning from errors: applying aviation safety concepts to medicine].
AB  - Health care safety levels range below other complex industries. Civil aviation
      has throughout its history developed methods and concepts that have made the
      airplane into one of the safest means of mass transport. Key elements are
      accident investigations that focus on cause instead of blame, human-centered
      design of machinery and processes, continuous training of all personnel and a
      shared safety culture. These methods and concepts can basically be applied to
      medicine which has successfully been achieved in certain areas, however, a
      comprehensive implementation remains to be completed. This applies particularly
      to including the topic of safety into relevant curricula. Physicians are obliged
      by the oath"primum nil nocere" to act, but economic as well as political pressure
      will eventually confine professional freedom if initiative is not taken soon.

PMID- 23150131
TI  - [Introduction of operating room checklists as a part of clinical risk management:
      are there hard facts on complication prevention available?].
AB  - For approximately the past 10 years the aspects of quality and risk management
      have spread widely not only into the realm of hospitals but also into overall
      general medicine, which is viewed by many physicians as a paradigmatic change.
      The required use of the WHO operating room (OR) checklist has in the meantime
      become routine procedure in many hospitals but with varying degrees of
      acceptance. Current data reaffirm the positive effect of the checklist in
      lowering complication and mortality rates. This effect can be directly traced to
      a higher level for safety culture in the OR.

PMID- 23150136
TI  - Primary culture of embryonic rat olfactory receptor neurons.
AB  - Embryonic cells are very robust in surviving dissection and culturing protocols
      and easily adapt to their in vitro environment. Despite these advantages,
      research in the olfactory field on cultured embryonic olfactory neurons is
      sparse. In this study, two primary rat olfactory explant cultures of different
      embryonic d (E17 and E20) were established, comprising epithelium and bulb. The
      functionality of these neurons was tested by measuring intracellular calcium
      responses to cAMP-inducing agents forskolin (FSK) and 3-isobutyl-1-methylxanthine
      (IBMX) with fluorescence microscopy. For E17, the responsive cell fraction
      increased over time, from an initial 3% at the 1 d in vitro (DIV) to a maximum of
      19% at 11 DIV. The response of E20 neurons fluctuated over time around a more or
      less stable 13%. A logistic regression analysis indicated a significant
      difference between both embryonic d in the response to FSK + IBMX. In addition,
      of these functional neurons, 23.3% of E17 and 54.3% of E20 cultures were
      responsive to the odorant isoamyl acetate.

PMID- 23150137
TI  - Lhx8 promote differentiation of hippocampal neural stem/progenitor cells into
      cholinergic neurons in vitro.
AB  - Lhx8, also named L3, is a recently identified member of the LIM homeobox gene
      family. Previously, we found acetylcholinesterase (AChE)-positive cells in
      fimbria-fornix (FF) transected rat hippocampal subgranular zone (SGZ). In the
      present study, we detected choline acetyltransferase (ChAT)-positive cholinergic
      cells in hippocampal SGZ after FF transaction, and these ChAT-positive cells were
      double labeled by Lhx8. Then we overexpressed Lhx8 during neural differentiation
      of hippocampal neural stem/progenitor cells on adherent conditions using
      lentivirus Lenti6.3-Lhx8. The result indicated that overexpression of Lhx8 did
      not affect the proportion of MAP2-positive neurons, but increased the proportion
      of ChAT-positive cells in vitro. These results suggested that FF-transected
      hippocampal niche promoted the ChAT/Lhx8-positive cholinergic neurons generation
      in rodent hippocampus, and Lhx8 was not associated with the MAP2-positive neurons
      differentiation on adherent conditions, but played a role in the specification of
      cholinergic neurons derived from hippocampal neural stem/progenitor cells in
      vitro.

PMID- 23150139
TI  - Efficient establishment of primary fibroblast cultures from the hawksbill sea
      turtle (Eretmochelys imbricata).
AB  - The hawksbill sea turtle (Eretmochelys imbricata) is a critically endangered
      species at a risk of extinction. Preservation of the genomic and cellular
      information of endangered animals is important for future genetic and biological
      studies. Here, we report the efficient establishment of primary fibroblast
      cultures from skin tissue of the hawksbill sea turtle. We succeeded in
      establishing 19 primary cultures from 20 hawksbill sea turtle individuals (a
      success rate of 95%). These cells exhibited a fibroblast-like morphology and grew
      optimally at a temperature of 26 degrees C, but experienced a loss of viability
      when cultured at 37 degrees C. Chromosomal analysis using the primary cells
      derived here revealed that hawksbill sea turtles have a 2n = 56 karyotype.
      Furthermore, we showed that our primary cell cultures are free of several fish
      related viruses, and this finding is important for preservation purposes. To our
      knowledge, this report is the first to describe primary cell cultures established
      from normal tissues of the hawksbill sea turtle. The results will contribute to
      the preservation of biodiversity, especially for the sea turtles that are
      critically endangered owing to human activities.

PMID- 23150138
TI  - Characterization of three newly established rat sarcoma cell clones.
AB  - Establishment of new animal models using selected cell lines with different
      behaviour is very important for cancer investigations. In this study, we describe
      three morphologically distinct rat sarcoma clones-C4, C7 and D6-isolated from the
      R5-28 cell line. Cells of all clones expressed vimentin, fibronectin, laminin,
      collagen IV and matrix metalloproteinases 2 and 9. However, desmin, cytokeratins
      8 and 18, ZO-1 and desmoplakins I and II were not detected. Significant
      proliferative capacity was documented by proliferating cell nuclear antigen
      expression and BrdU positivity. Karyotype of the C4, C7 and D6 cells greatly
      differed from diploid chromosome number of normal rat somatic cells. High
      expression of three cytokines-monocyte chemoattractant protein 1, tissue
      inhibitor of metalloproteinases 1 and vascular endothelial growth factor-was
      observed in all three clones. However, they varied in concentration of chemokines
      associated with neutrophil migration and activation-cytokine induced neutrophil
      chemoattractant 2 and lipopolysaccharide induced CXC chemokine. The C4 clone
      showed spontaneous tumour regression in vivo that was associated with significant
      changes in lymphocyte subpopulations.

PMID- 23150140
TI  - Controlled activity of mouse astrocytes on electrospun PCL nanofiber containing
      polysaccharides from brown seaweed.
AB  - The central nervous system (CNS), once injured, rarely recovers original function
      mainly due to its limited regeneration ability. Astrocytes are cells that play
      critical roles in neural regeneration. Several biomaterials have been studied to
      replace and regenerate lost tissues within injured CNS. Seaweeds have
      extracellular polymeric substances (EPS) with bioactive properties such as
      antiviral and antioxidant properties. In this study, astrocyte activity was
      assessed, after being cultured on an electrospun polycaprolactone (PCL)
      nanofibrous mat containing a brown seaweed EPS. Laminarin and fucoidan, two main
      components of EPS extract from the brown seaweed, were concluded to increase or
      decrease astrocyte activity with respect to their concentration. When the
      concentration was under 10 MUg/ml, the astrocytes tended to increase their
      viability. In contrast, over 10 MUg/ml EPS in media suppressed the viability of
      astrocytes. In addition, when contained in PCL nanofiber, the EPS extract was
      also proven to influence astrocyte activity in the same way as the case when
      astrocytes were exposed to EPS in solution. This implies that the brown seaweed
      EPS-PCL nanofiber mat can be used for temporal control of astrocyte activity by
      EPS concentration. Through this research, we propose that the electrospun EPS-PCL
      nanofiber could be used as a nanomedicine or scaffold to treat CNS injuries.

PMID- 23150141
TI  - Divided consciousness: dissociation in DSM-5.

PMID- 23150142
TI  - Pilot intervention outcomes of an educational program for biospecimen research
      participation.
AB  - Biospecimen banking programs are critically dependent on participation of diverse
      population members. The purpose of this study was to test a pilot intervention to
      enhance recruitment to a biospecimen bank among racially diverse community
      members. A mixed methods, community-based participatory research (CBPR)
      orientation was used to develop and pilot an intervention to educate and recruit
      participants to a biospecimen bank. Pre- and post-assessments of knowledge about
      research, perceived costs and benefits of participation (expected utility), and
      emotional states associated with research participation (affective associations)
      as well as post-intervention participation in biobanking were examined to
      determine intervention effectiveness. The pilot intervention educated 148
      community members; 107 (73 %) donated blood and 77 (52 %) completed a 36-page
      lifestyle questionnaire. Thirty-two percent of participants were African American
      and 11 % were Native American. Participating in the educational program
      significantly reduced negative affect associated with research involving
      collection of genetic material or completion of a survey. Improved knowledge and
      understanding of biobanking and research through a CBPR approach are likely to
      increase participation rates in biobanking for diverse community members.
      Accurate information and improved knowledge can reduce individual anxiety and
      concerns that serve as barriers to research participation.

PMID- 23150143
TI  - The reporting of blinding in physical medicine and rehabilitation randomized
      controlled trials: a systematic review.
AB  - OBJECTIVE: To conduct a systematic review evaluating the reporting of blinding in
      randomized controlled trials published in the field of Physical Medicine and
      Rehabilitation over two time periods. DATA SOURCES: We searched MEDLINE via
      PubMed for all randomized controlled trials published in American Journal of
      Physical Medicine and Rehabilitation, Archives of Physical Medicine and
      Rehabilitation, Clinical Rehabilitation, Disability and Rehabilitation and
      (Scandinavian) Journal of Rehabilitation Medicine in the years 2000 and 2010.
      STUDY SELECTION: We initially identified 222 articles, and 139 (62.6%) met our
      selection criteria. DATA EXTRACTION: Two independent investigators collected data
      regarding study characteristics and blinding from each article. Consistency of
      data extraction was evaluated. DATA SYNTHESIS: When comparing articles from 2010
      and 2000, the former showed significantly higher rates for reporting of blinding,
      explicitly describing key persons' blinding status, and discussing the absence of
      blinding as a study limitation. There was a trend for lower reporting among
      trials with positive outcomes. No improvement was observed in other CONSORT
      enforced parameters. CONCLUSIONS: Although the reporting of blinding in Physical
      Medicine and Rehabilitation randomized controlled trials shows some improvement
      over the past decade, it still does not fulfill current recommendations. Given
      its critical role in determining internal validity, stricter enforcement of
      CONSORT guidelines is needed.

PMID- 23150144
TI  - A novel monthly dosing regimen of risedronate for the treatment of postmenopausal
      osteoporosis: 2-year data.
AB  - This 2-year trial evaluated the efficacy and tolerability of a monthly oral
      regimen of risedronate. Postmenopausal women with osteoporosis were randomly
      assigned to double-blind treatment with risedronate 75 mg on 2 consecutive days
      each month (2CDM) or 5 mg daily. The primary end point was the percentage change
      from baseline in lumbar spine bone mineral density (BMD) at 12 months. Secondary
      end points included the change in BMD of the lumbar spine and proximal femur and
      in bone turnover markers as well as the number of subjects with at least one new
      vertebral fracture over 24 months. Among 1,229 patients who were randomized and
      received at least one dose of risedronate, lumbar spine BMD was increased in both
      treatment groups: mean percentage change from baseline was 4.2 +/- 0.19 and 4.3
      +/- 0.19 % in the 75 mg 2CDM and 5 mg daily groups, respectively, at month 24.
      The treatment difference was 0.17 (95 % confidence interval -0.35 to 0.68). There
      were no statistically significant differences between treatment groups on any
      secondary efficacy parameters. Both treatment regimens were well tolerated.
      Risedronate 75 mg 2CDM was noninferior in BMD efficacy and did not show a
      difference in tolerability compared to 5 mg daily after 24 months of treatment in
      women with postmenopausal osteoporosis. This monthly regimen may provide a more
      convenient dosing schedule to some patients with postmenopausal osteoporosis.

PMID- 23150145
TI  - Forster resonance energy transfer in a nanoscopic system on a dielectric
      interface.
AB  - We investigate picosecond-resolved energy transfer between a quantum dot (donor)
      and an organic molecule (acceptor) in the proximity of a reflecting  metallic/non
      metallic surface. We demonstrate experimentally that the Forster resonance energy
      transfer (FRET) is significantly influenced by the proximity of the mirror.
      Locating a cadmium selenide quantum dot (donor: D) attached to an organic dye
      merocyanine (acceptor: A) at well-defined positions from the reflecting
      silver/silicon surface allows the transfer rate to be determined as a function of
      distance from the surface. An attempt to fit the experimental data to a model
      relying upon the change of the apparent energy transfer rate due to interference
      of direct and reflected light waves reveals reasonably good results. The results
      show that the observed FRET rate in a D-A pair on the mirror surface is
      oscillating in nature, providing information for the measured energy transfer,
      which could be potentially different from that of the actual transfer due to
      optical interference.

PMID- 23150146
TI  - Role of iron carbonyls in the inhibition of oxygen activation for the oxidation
      of CO catalyzed by iron oxide-supported gold.
AB  - Iron oxide-supported gold samples were prepared by co-precipitation from HAuCl(4)
      and Fe(NO(3))(3). The activities of the samples as CO oxidation catalysts were
      tested without thermal treatment and following treatments in flows of He and O(2)
      at various temperatures. It was found that the untreated samples and those
      treated in a flow of He at 150  degrees C were more active than samples that had
      been treated at 400  degrees C in either a flow of O(2) or of He. Infrared
      spectra recorded during CO oxidation catalysis indicate the presence of bonded CO
      molecules to cationic gold on all samples, whereas spectra of the least active
      catalysts indicate a predominant presence of Fe(2+) carbonyls, which were highly
      stable under the conditions of our experiments. Our results indicate that in the
      least active samples the Fe(2+)-bound CO blocks sites that would otherwise be
      available for oxygen activation.

PMID- 23150147
TI  - Reciprocal inhibition and slow calcium decay in perigeniculate interneurons
      explain changes of spontaneous firing of thalamic cells caused by cortical
      inactivation.
AB  - The role of cortical feedback in the thalamocortical processing loop has been
      extensively investigated over the last decades. With an exception of several
      cases, these searches focused on the cortical feedback exerted onto thalamo
      cortical relay (TC) cells of the dorsal lateral geniculate nucleus (LGN). In a
      previous, physiological study, we showed in the cat visual system that cessation
      of cortical input, despite decrease of spontaneous activity of TC cells,
      increased spontaneous firing of their recurrent inhibitory interneurons located
      in the perigeniculate nucleus (PGN). To identify mechanisms underlying such
      functional changes we conducted a modeling study in NEURON on several networks of
      point neurons with varied model parameters, such as membrane properties, synaptic
      weights and axonal delays. We considered six network topologies of the retino
      geniculo-cortical system. All models were robust against changes of axonal delays
      except for the delay between the LGN feed-forward interneuron and the TC cell.
      The best representation of physiological results was obtained with models
      containing reciprocally connected PGN cells driven by the cortex and with
      relatively slow decay of intracellular calcium. This strongly indicates that the
      thalamic reticular nucleus plays an essential role in the cortical influence over
      thalamo-cortical relay cells while the thalamic feed-forward interneurons are not
      essential in this process. Further, we suggest that the dependence of the
      activity of PGN cells on the rate of calcium removal can be one of the key
      factors determining individual cell response to elimination of cortical input.

PMID- 23150150
TI  - Personalizing antiplatelet therapy-moving to clinics.

PMID- 23150149
TI  - NAT2 genotype guided regimen reduces isoniazid-induced liver injury and early
      treatment failure in the 6-month four-drug standard treatment of tuberculosis: a
      randomized controlled trial for pharmacogenetics-based therapy.
AB  - OBJECTIVE: This study is a pharmacogenetic clinical trial designed to clarify
      whether the N-acetyltransferase 2 gene (NAT2) genotype-guided dosing of isoniazid
      improves the tolerability and efficacy of the 6-month four-drug standard regimen
      for newly diagnosed pulmonary tuberculosis. METHODS: In a multicenter, parallel,
      randomized, and controlled trial with a PROBE design, patients were assigned to
      either conventional standard treatment (STD-treatment: approx. 5 mg/kg of
      isoniazid for all) or NAT2 genotype-guided treatment (PGx-treatment: approx. 7.5
      mg/kg for patients homozygous for NAT2 4: rapid acetylators; 5 mg/kg, patients
      heterozygous for NAT2 4: intermediate acetylators; 2.5 mg/kg, patients without
      NAT2 4: slow acetylators). The primary outcome included incidences of 1)
      isoniazid-related liver injury (INH-DILI) during the first 8 weeks of therapy,
      and 2) early treatment failure as indicated by a persistent positive culture or
      no improvement in chest radiographs at the 8th week. RESULTS: One hundred and
      seventy-two Japanese patients (slow acetylators, 9.3 %; rapid acetylators, 53.5
      %) were enrolled in this trial. In the intention-to-treat (ITT) analysis, INH
      DILI occurred in 78 % of the slow acetylators in the STD-treatment, while none of
      the slow acetylators in the PGx-treatment experienced either INH-DILI or early
      treatment failure. Among the rapid acetylators, early treatment failure was
      observed with a significantly lower incidence rate in the PGx-treatment than in
      the STD-treatment (15.0 % vs. 38 %). Thus, the NAT2 genotype-guided regimen
      resulted in much lower incidences of unfavorable events, INH-DILI or early
      treatment failure, than the conventional standard regimen. CONCLUSION: Our
      results clearly indicate a great potential of the NAT2 genotype-guided dosing
      stratification of isoniazid in chemotherapy for tuberculosis.

PMID- 23150152
TI  - Structure and compositional control of MoO3 hybrids assembled by nanoribbons for
      improved pseudocapacitor rate and cycle performance.
AB  - Hierarchical structures of transition metal oxides with well-defined compositions
      are crucial for achieving advanced electrodes for energy storage devices. Herein,
      we first demonstrate the hierarchically structured MoO(3) assembled by twisted
      nanoribbons with a hybrid composition for improved rate capability and cycle
      stability of the pseudocapacitor. The hierarchical, flower-like structures of
      MoO(3) assembled by hybrid nanoribbons were induced by the specific interactions
      of MoO(3) interlayers with ionic liquids (ILs), as proven by spectroscopic and
      electrochemical analyses. Furthermore, the interlayer modification of MoO(3)
      crystallites through IL interaction enabled unique pseudocapacitive behaviors for
      fast and reversible proton intercalation/extraction that could not be observed by
      conventional MoO(3). In this research, we used control samples to prove our
      hypothesis that the capacitor performances of MoO(3) can be improved by a
      hierarchical structure and hybrid composition. These structural and compositional
      features of the hybrids greatly enhanced the rate capability by fast ion
      diffusion while improving cycle stability due to efficient stress release. More
      importantly, we observed the dramatic enhancement of ion diffusion coefficients
      of hybrids for good rate capability, because ion diffusion into the layered
      structure is very critical for maintaining specific capacitance at the high
      current density. The facilitated ion diffusion is attributed to the hierarchical
      nanostructure for a short diffusion length and ion accessibility, the high ion
      mobility in hybrids, and the interlayer modification of MoO(3) by IL coating.
      Therefore, this research offers new insight into the rational design of advanced
      electrode materials on the basis of the hierarchical complex structures of
      transition metal oxides with well-defined hybrid compositions for future
      applications in energy conversion and storage.

PMID- 23150151
TI  - Effect of the CYP2C19 2 and 3 genotypes, ABCB1 C3435T and PON1 Q192R alleles on
      the pharmacodynamics and adverse clinical events of clopidogrel in Chinese people
      after percutaneous coronary intervention.
AB  - PURPOSE: Chinese people are more frequent carriers of cytochrome P450 2C19
      (CYP2C19) loss-of-function alleles than Caucasians. The effect of the ATP-binding
      cassette, sub-family B, member 1 (ABCB1), and paraoxonase 1 (PON1) variants on
      platelet reactivity and clinical outcomes of clopidogrel treatment has not yet
      been reported in Chinese patients after percutaneous coronary intervention. The
      aim of this study was to investigate the effect of the CYP2C19, ABCB1, and PON1
      variants on clopidogrel pharmacodynamics and clinical outcomes in these patients.
      METHODS: Six hundred and seventy patients after percutaneous coronary
      intervention were enrolled in a single-center registry. The antiplatelet effect
      of clopidogrel was assessed by thromboelastography, and the CYP2C19, ABCB1, and
      PON1 genotypes were detected by the ligase detection reaction. Primary clinical
      endpoints included cardiovascular death, nonfatal myocardial infarction, target
      vessel revascularization, and stent thrombosis. The secondary clinical endpoints
      were thrombolysis in myocardial infarction bleeding. The follow-up period was 12
      months. RESULTS: The frequency of the CYP2C19 loss-of-function alleles was
      relatively high (57.3 %). The risk of a low response to clopidogrel and composite
      ischemic events increased with the number of CYP2C19 loss-of-function alleles.
      However, there were not significant differences in clopidogrel pharmacodynamics
      and clinical outcomes across the ABCB1 and PON1 genotype groups; bleeding was not
      significantly different across the CYP2C19, ABCB1, and PON1 genotype groups.
      CONCLUSIONS: The CYP2C19 loss-of-function alleles had a gene dose effect on the
      pharmacodynamics and composite ischemic events of clopidogrel in our study
      population. Neither the ABCB1 nor the PON1 genotype significantly influenced the
      antiplatelet effect and clinical outcomes of clopidogrel in these patients.

PMID- 23150153
TI  - Management of unilateral true vocal cord paralysis in children.
AB  - PURPOSE OF REVIEW: Historically, information gained from the treatment of
      unilateral true vocal cord paralysis (UVCP) in adults was the same used to treat
      children. Today, there is a growing body of literature aimed specifically at the
      treatment of this condition in children. It is an area of growing interest as
      UVCP can significantly impact a child's quality of life. RECENT FINDINGS:
      Children with UVCP may present with stridor, dysphonia, aspiration, feeding
      difficulties, or a combination of these symptoms. Diagnosis relies on
      laryngoscopy, but other adjuncts such as ultrasound and laryngeal
      electromyography may also be helpful in making the diagnosis and forming a
      treatment plan. In many instances, there is effective compensation by the
      contralateral vocal fold, making surgical intervention unnecessary. Children who
      cannot compensate for a unilateral defect may suffer from significant dysphonia
      that can affect their quality of life because their ability to be understood may
      be diminished. In these patients, treatment in the form of medialization or
      reinnervation of the affected recurrent laryngeal nerve may be warranted.
      SUMMARY: UVCP is a well recognized problem in pediatric patients with disordered
      voice and feeding problems. Some patients will spontaneously recover their
      laryngeal function. For those who do not, a variety of reliable techniques are
      available for rehabilitative treatment. Improved diagnostics and a growing
      understanding of prognosis can help guide therapy decisions along with the goals
      and desires of the patient and his or her family.

PMID- 23150154
TI  - Anatomical considerations in multiligament knee injury and surgery.
AB  - The management of multiligament knee injury mandates a comprehensive
      understanding of the anatomy on all sides of the joint. Imperative to repair or
      reconstructive procedures is an intimate knowledge of the structure of the
      cruciate and collateral ligaments, as well as the complex confluence of
      structures that comprise the posteromedial and posterolateral corners. Beyond the
      ligamentous anatomy, the surgeon must also be aware of the potential for
      neurologic and vascular compromise-both from injury and from treatment-that can
      often complicate multiligament knee injuries. In this article, we outline the
      basic anatomy and biomechanical function of the ligamentous structures of the
      knee, structures at risk, and the patterns of injury seen with knee dislocations
      and multiple ligament knee injuries in general.

PMID- 23150155
TI  - Initial evaluation of the acute and chronic multiple ligament injured knee.
AB  - Multiple ligament injuries of the knee are rare, and severe injuries are often
      present following a knee dislocation. Appropriate initial evaluation and
      management is of critical importance for maximizing the potential outcome and
      avoiding disastrous consequences associated with these difficult injuries. While
      many of these injuries present acutely in an emergency department or clinic,
      presentation on a delayed basis is not uncommon. Injuries can present in a
      variety of situations, such as an isolated knee injury in an athlete or as part
      of a multisystem-injured trauma patient. In this publication, we review the
      etiology, classification, and comprehensive initial evaluation of the acute and
      chronic multiple-ligament injured knee.

PMID- 23150156
TI  - Current concepts in knee dislocations: PCL, ACL, and medial sided injuries.
AB  - Dislocations resulting in multiligament knee injuries are challenging to treat
      and diagnose. With proper diagnosis and anatomic reconstruction techniques,
      patients can have successful outcomes. This article describes the senior author's
      (J.P.S.'s) preferred reconstruction techniques, timing for surgery, and
      rehabilitation techniques for injuries involving the anterior cruciate ligament
      (ACL), posterior cruciate ligament (PCL), and posteromedial corner (PMC). We
      prefer to address these injuries in a staged fashion. The PCL, PMC, and any
      additional meniscal pathology are addressed in the index procedure. The ACL is
      reconstructed approximately 6 weeks later to ensure that acceptable range of
      motion has been regained. Staging procedures also allow time to maximize
      rehabilitation protocols for both the PCL and the ACL.

PMID- 23150157
TI  - Treatment of PCL, ACL, and lateral-side knee injuries: acute and chronic.
AB  - Combined posterior cruciate ligament, anterior cruciate ligament, and lateral
      side disruption is one of the more common patterns of multiligament knee injury.
      This is a devastating injury with significant long-term functional sequelae,
      making accurate diagnosis and management extremely important. While surgical
      intervention is necessary to restore function, the specific management strategies
      remain controversial. This article will review the current literature and the
      authors' preferred approach including physical examination, imaging, timing of
      surgery, surgical technique, and postoperative rehabilitation.

PMID- 23150158
TI  - Surgical treatment of combined PCL-ACL medial and lateral side injuries (global
      laxity): surgical technique and 2- to 18-year results.
AB  - The multiple ligament injured knee is a severe injury that may also involve
      neurovascular injuries, fractures, and other systemic injuries. Surgical
      treatment offers good functional results documented in the literature by physical
      examination, arthrometer testing, stress radiography, and knee ligament rating
      scales. Mechanical tensioning devices are helpful with cruciate ligament
      tensioning. Some low grade medial collateral ligament (MCL) complex injuries may
      be amenable to brace treatment, while high grade medial side injuries require
      combined surgical repair-reconstruction. Lateral posterolateral injuries are most
      successfully treated with combined surgical repair-reconstruction. Surgical
      timing in acute multiple ligament injured knee cases depends on the ligaments
      injured, injured extremity vascular status, skin condition of the extremity,
      degree of instability, and the patients overall health. Allograft tissue is
      preferred for these complex surgical procedures. Delayed reconstruction of 2 to 3
      weeks may decrease the incidence of arthrofibrosis, and it is important to
      address all components of the instability. Currently, there is no conclusive
      evidence that double-bundle posterior cruciate ligament (PCL) reconstruction
      provides superior results to single-bundle PCL reconstruction in the multiple
      ligament injured knee. The purpose of this article is to discuss G.F.'s surgical
      technique for combined PCL and anterior cruciate ligament, medial, and lateral
      side reconstructions in acute and chronic multiple ligament injured knees with
      global laxity. This article will focus on recognizing and defining the
      instability pattern, the use of external fixation, surgical timing, graft
      selection and preparation, G.F.'s preferred surgical technique, mechanical graft
      tensioning, perioperative antibiotics, specialized operating teams, postoperative
      rehabilitation, and our results of treatment in these complex surgical cases.

PMID- 23150159
TI  - Outcomes of treatment of multiple ligament knee injuries.
AB  - Knee dislocations are rare and potentially devastating injuries. Significant
      displacement of the tibia and femur commonly disrupts multiple knee ligaments and
      also often results in profound disruption to the surrounding soft tissue
      envelope. Open wounds and neurologic and vascular insult can put the involved
      limb in jeopardy. Following reduction, the optimal management of the dislocated
      knee is unknown. Surgery to repair and/or reconstruct torn structures likely
      affords superior long-term function over nonoperative immobilization strategies.
      The role of early versus delayed surgery, repair versus reconstruction, and
      autograft versus allograft tissue for reconstruction remain topics of debate.
      High-quality research efforts to investigate these controversies are hampered by
      the heterogeneous nature of the injuries themselves and the many treatment
      strategies available.

PMID- 23150160
TI  - Tendon transfers for peroneal nerve injuries in the multiple ligament injured
      knee.
AB  - Although knee dislocations are relatively rare injuries; associated drop foot
      complication as a consequence of common peroneal nerve palsy (CPN) is
      substantially high. Even after successful ligament constructions; unresolved CPN
      palsy is a factor contributing to bad outcome after knee dislocations. CPN palsy
      is seen more after open dislocations, rotatory dislocations, and especially in
      patients with posterolateral corner injuries. CPN palsy can readily be diagnosed
      clinically, although high index of suspicion is needed. Surgical exploration in
      the acute setting is still debatable. Conservative management can be appropriate
      in early phase of treatment, however surgery is the choice of treatment for
      persistent nerve damage. Neurolysis, primary nerve repair, nerve grafting, and
      posterior tibialis tendon transfer are all reasonable choices for surgical
      treatment. Late surgery results have an exceedingly low success. Tibialis
      posterior tendon transfer is indicated primarily in the setting of a drop foot
      and a steppage gait. Tibialis posterior tendon transfer procedures have had
      acceptable success in allowing patients to return to ambulation without assistive
      device.

PMID- 23150161
TI  - Quadriceps tendon rupture: a biomechanical comparison of transosseous equivalent
      double-row suture anchor versus transosseous tunnel repair.
AB  - Quadriceps rupture off the patella is traditionally repaired by a transosseous
      tunnel technique, although a single-row suture anchor repair has recently been
      described. This study biomechanically tested a new transosseous equivalent (TE)
      double-row suture anchor technique compared with the transosseous repair for
      quadriceps repair. After simulated quadriceps-patella avulsion in 10 matched
      cadaveric knees, repairs were completed by either a three tunnel transosseous (TT
      = 5) or a TE suture anchor (TE = 5) technique. Double-row repairs were done using
      two 5.5 Bio-Corkscrew FT (fully threaded) (Arthrex, Inc., Naples, FL, USA) and
      two 3.5 Bio-PushLock anchors (Arthrex, Inc., Naples, FL, USA) with all 10 repairs
      done with #2 FiberWire suture (Arthrex, Inc., Naples, FL). Cyclic testing from 50
      to 250 N for 250 cycles and pull to failure load (1 mm/s) were undertaken. Gap
      formation and ultimate tensile load (N) were recorded and stiffness data (N/mm)
      were calculated. Statistical analysis was performed using a Mann-Whitney U test
      and survival characteristics examined with Kaplan-Meier test. No significant
      difference was found between the TE and TT groups in stiffness (TE = 134 +/- 15
      N/mm, TT = 132 +/- 26 N/mm, p = 0.28). The TE group had significantly less
      ultimate tensile load (N) compared with the TT group (TE = 447 +/- 86 N, TT = 591
      +/- 84 N, p = 0.04), with all failures occurring at the suture eyelets. Although
      both quadriceps repairs were sufficiently strong, the transosseous repairs were
      stronger than the TE suture anchor repairs. The repair stiffness and gap
      formation were similar between the groups.

PMID- 23150162
TI  - Validation of a novel smartphone accelerometer-based knee goniometer.
AB  - Loss of full knee extension following anterior cruciate ligament surgery has been
      shown to impair knee function. However, there can be significant difficulties in
      accurately and reproducibly measuring a fixed flexion of the knee. We studied the
      interobserver and the intraobserver reliabilities of a novel, smartphone
      accelerometer-based, knee goniometer and compared it with a long-armed
      conventional goniometer for the assessment of fixed flexion knee deformity. Five
      healthy male volunteers (age range 30 to 40 years) were studied. Measurements of
      knee flexion angle were made with a telescopic-armed goniometer (Lafayette
      Instrument, Lafayette, IN) and compared with measurements using the smartphone
      (iPhone 3GS, Apple Inc., Cupertino, CA) knee goniometer using a novel
      trigonometric technique based on tibial inclination. Bland-Altman analysis of
      validity and reliability including statistical analysis of correlation by
      Pearson's method was undertaken. The iPhone goniometer had an interobserver
      correlation (r) of 0.994 compared with 0.952 for the Lafayette. The intraobserver
      correlation was r = 0.982 for the iPhone (compared with 0.927). The datasets from
      the two instruments correlate closely (r = 0.947) are proportional and have mean
      difference of only -0.4 degrees (SD 3.86 degrees). The Lafayette goniometer had
      an intraobserver reliability +/- 9.6 degrees. The interobserver reliability was
      +/- 8.4 degrees. By comparison the iPhone had an interobserver reliability +/-
      2.7 degrees and an intraobserver reliability +/- 4.6 degrees. We found the iPhone
      goniometer to be a reliable tool for the measurement of subtle knee flexion in
      the clinic setting.

PMID- 23150163
TI  - Computer navigated versus conventional total knee arthroplasty.
AB  - In total knee arthroplasty (TKA), reconstruction of a neutral mechanical axis is
      of great importance. The main goal of this study was to compare the accuracy of
      alignment after conventional versus computer-assisted TKA. Additionally, the
      effect of computer-assisted surgery (CAS) on functional outcome was analyzed. Out
      of a consecutive series, 50 conventional TKA were compared with 50 computer
      assisted TKA. Except for the use of CAS, all perioperative and postoperative
      interventions were comparable. Radiological outcome was analyzed on standardized
      standing long-leg radiographs. Functional outcome was assessed using the Oxford
      Knee Score (OKS) and the Knee Society Score (KSS). No significant difference in
      mean mechanical axis alignment between the two groups was found. The number of
      outliers deviating more than 3 degrees from the mechanical axis was significantly
      reduced by using CAS, with 50% outliers in the conventional group and 26%
      outliers in the CAS group (p = 0.023). At midterm follow-up, the OKS and KSS knee
      and function scores did not show statistical difference between the two groups.
      The present study showed a reduction of the number of outliers exceeding 3
      degrees from the tibiofemoral mechanical axis using CAS-TKA. This improvement in
      accuracy did not result in improvement of the functional outcome at mid-term
      follow-up.

PMID- 23150167
TI  - Inactivation of Cdc42 in embryonic brain results in hydrocephalus with ependymal
      cell defects in mice.
AB  - The establishment of a polarized cellular morphology is essential for a variety
      of processes including neural tube morphogenesis and the development of the
      brain. Cdc42 is a Ras-related GTPase that plays an essential role in controlling
      cell polarity through the regulation of the actin and microtubule cytoskeleton
      architecture. Previous studies have shown that Cdc42 plays an indispensable role
      in telencephalon development in earlier embryo developmental stage (before
      E12.5). However, the functions of Cdc42 in other parts of brain in later embryo
      developmental stage or in adult brain remain unclear. Thus, in order to address
      the role of Cdc42 in the whole brain in later embryo developmental stage or in
      adulthood, we used Cre/loxP technology to generate two lines of tissue-specific
      Cdc42-knock-out mice. Inactivation of Cdc42 was achieved in neuroepithelial cells
      by crossing Cdc42/ flox mice with Nestin-Cre mice and resulted in hydrocephalus,
      causing death to occur within the postnatal stage. Histological analyses of the
      brains from these mice showed that ependymal cell differentiation was disrupted,
      resulting in aqueductal stenosis. Deletion of Cdc42 in the cerebral cortex also
      induced obvious defects in interkinetic nuclear migration and hypoplasia. To
      further explore the role of Cdc42 in adult mice brain, we examined the effects of
      knocking-out Cdc42 in radial glial cells by crossing Cdc42/flox mice with human
      glial fibrillary acidic protein (GFAP)-Cre mice. Inactivation of Cdc42 in radial
      glial cells resulted in hydrocephalus and ependymal cell denudation. Taken
      together, these results highlight the importance of Cdc42 for ependymal cell
      differentiation and maintaining, and suggest that these functions likely
      contribute to the essential roles played by Cdc42 in the development of the
      brain.

PMID- 23150165
TI  - MicroRNA-548 down-regulates host antiviral response via direct targeting of IFN
      lambda1.
AB  - Interferon (IFN)-mediated pathways are a crucial part of the cellular response
      against viral infection. Type III IFNs, which include IFN-lambda1, 2 and 3,
      mediate antiviral responses similar to Type I IFNs via a distinct receptor
      complex. IFN-lambda1 is more effective than the other two members. Transcription
      of IFN-lambda1 requires activation of IRF3/7 and nuclear factor-kappa B (NF
      kappaB), similar to the transcriptional mechanism of Type I IFNs. Using reporter
      assays, we discovered that viral infection induced both IFN-lambda1 promoter
      activity and that of the 3'-untranslated region (UTR), indicating that IFN
      lambda1 expression is also regulated at the post-transcriptional level. After
      analysis with microRNA (miRNA) prediction programs and 3'UTR targeting site
      assays, the miRNA-548 family, including miR-548b-5p, miR-548c-5p, miR-548i, miR
      548j, and miR-548n, was identified to target the 3'UTR of IFN-lambda1. Further
      study demonstrated that miRNA-548 mimics down-regulated the expression of IFN
      lambda1. In contrast, their inhibitors, the complementary RNAs, enhanced the
      expression of IFN-lambda1 and IFN-stimulated genes. Furthermore, miRNA-548 mimics
      promoted infection by enterovirus-71 (EV71) and vesicular stomatitis virus (VSV),
      whereas their inhibitors significantly suppressed the replication of EV71 and
      VSV. Endogenous miRNA-548 levels were suppressed during viral infection. In
      conclusion, our results suggest that miRNA-548 regulates host antiviral response
      via direct targeting of IFN-lambda1, which may offer a potential candidate for
      antiviral therapy.

PMID- 23150168
TI  - Weight status, quality of life, and cigarette smoking among adolescents in
      Washington State.
AB  - PURPOSE: We examine age- and sex-specific associations between weight status and
      intensity of cigarette smoking in a large sample of adolescents. Additionally, we
      test whether quality of life (QOL) and weight control behaviors (i.e., trying to
      lose, gain, or stay the same weight) mediate the association. METHODS: We used
      cross-sectional data from the 2010 Washington State Healthy Youth Survey
      collected in grades 8, 10, and 12 (n = 11,222). Multinomial logistic regression
      was used to model cigarette smoking (none, light, frequent) as a function of
      weight status, weight control behaviors, and QOL by sex and age. Indirect effects
      of presumed mediators were assessed using the product of coefficients approach.
      RESULTS: Weight status was not associated with smoking. Trying to stay the same
      weight was associated with lower odds of light smoking for younger girls (OR =
      0.25; 95% CI = 0.08, 0.84), whereas trying to lose weight was associated with
      higher odds of light smoking for older girls (OR = 1.73; 95% CI = 1.11, 2.70).
      Low QOL was associated with higher odds of light and frequent smoking for both
      girls and boys (P < 0.001). The mediation effects of weight control behavior and
      QOL combined were significant in the associations between body mass index
      percentile and smoking among older girls. CONCLUSION: Targeted interventions
      designed to promote QOL and healthy weight control behaviors among youth may help
      to decrease the prevalence of smoking.

PMID- 23150169
TI  - Morphological and functional asymmetry of the human recurrent laryngeal nerve.
AB  - PURPOSE: The aim of the current study was to analyze some parameters that are
      involved in nerve conduction in the right and left recurrent laryngeal nerves
      (RLNs) in humans. We have studied two morphological parameters such as the length
      of the two nerves, and the total intraperineural area (TIPA) from necropsies, and
      one functional parameter such as the latency of the thyroarytenoid muscle from
      operated patients. METHODS: The morphological parameters of six white female
      adult cadavers were analyzed. The RLNs were totally removed on both sides with
      the vagus nerve from their origin to the entrance in the larynx at the
      cricothyroid joint. The lengths were measured with the help of a digitalized
      caliper. Selected sections were obtained from each third of the RLNs for
      histological analysis. The TIPA was estimated at each selected level using
      digitized images of nerve sections and a manual micrometer. All the measurements
      were carried out by specialists in histology. The intraoperative vagal nerve
      stimulations were conducted using the NIM3 Medtronic((r)) monitoring system
      (Medtronic Xomed Inc., Jacksonville, FL, USA) in ten adult patients without
      laryngeal or nervous disease during thyroid gland surgery. The evocated laryngeal
      electromyography was performed with the Medtronic bipolar needle electrode
      directly inserted into the thyroarytenoid muscle. The direct vagal nerve
      stimulation was achieved with the Medtronic stimulation from 0.5 to 1 mA. The
      latency of the thyroarytenoid muscle was recorded on the NIM-response monitor.
      RESULTS: The mean lengths of the left and right RLNs were, respectively, 136.6
      and 75.0 mm with a mean difference of 61.6 mm (range 50-75 mm). The quantitative
      comparison of the TIPA between proximal segments of the left and right RLN showed
      no significant difference. The distal and proximal TIPA ratio demonstrated
      differences between the left and right RLN, respectively, 53.76 and 38.88 %
      without any statistical meaning. The comparison of the TIPA of the distal
      segments of the RLNs showed no significant difference. The intraoperative vagal
      nerve stimulation (0.5 and 1 mA) displayed a mean latency of the right and left
      thyroarytenoid muscle, respectively, of 3.55-3.68 and 5.90-5.98 ms with a mean
      difference of 2.35-2.30 ms (range 1.75-3.30 ms). CONCLUSION: If length and
      latency asymmetry of the right and left RLNs in humans can be demonstrated, the
      synchronicity of the vocal folds requiring precise controlled variations within
      intrinsic laryngeal muscles needs further investigations.

PMID- 23150172
TI  - Successful treatment with alitretinoin of dissecting cellulitis of the scalp in
      keratitis-ichthyosis-deafness syndrome.

PMID- 23150170
TI  - Big effects of small RNAs: a review of microRNAs in anxiety.
AB  - Epigenetic and regulatory elements provide an additional layer of complexity to
      the heterogeneity of anxiety disorders. MicroRNAs (miRNAs) are a class of small,
      noncoding RNAs that have recently drawn interest as epigenetic modulators of gene
      expression in psychiatric disorders. miRNAs elicit their effects by binding to
      target messenger RNAs (mRNAs) and hindering translation or accelerating
      degradation. Considering their role in neuronal differentiation and synaptic
      plasticity, miRNAs have opened up new investigative avenues in the aetiology and
      treatment of anxiety disorders. In this review, we provide a thorough analysis of
      miRNAs, their targets and their functions in the central nervous system (CNS),
      focusing on their role in anxiety disorders. The involvement of miRNAs in CNS
      functions (such as neurogenesis, neurite outgrowth, synaptogenesis and synaptic
      and neural plasticity) and their intricate regulatory role under stressful
      conditions strongly support their importance in the aetiology of anxiety
      disorders. Furthermore, miRNAs could provide new avenues for the development of
      therapeutic targets in anxiety disorders.

PMID- 23150171
TI  - A non-transgenic mouse model (icv-STZ mouse) of Alzheimer's disease: similarities
      to and differences from the transgenic model (3xTg-AD mouse).
AB  - Alzheimer's disease (AD) can be divided into sporadic AD (SAD) and familial AD
      (FAD). Most AD cases are sporadic and result from multiple etiologic factors,
      including environmental, genetic, and metabolic factors, whereas FAD is caused by
      mutations in the presenilins or amyloid-beta (Abeta) precursor protein (APP)
      genes. A commonly used animal model for AD is the 3xTg-AD transgenic mouse model,
      which harbors mutated presenilin 1, APP, and tau genes and thus represents a
      model of FAD. There is an unmet need in the field to characterize animal models
      representing different AD mechanisms, so that potential drugs for SAD can be
      evaluated preclinically in these animal models. A mouse model generated by
      intracerebroventricular (icv) administration of streptozocin (STZ), the icv-STZ
      mouse, shows many aspects of SAD. In this study, we compared the non-cognitive
      and cognitive behaviors as well as biochemical and immunohistochemical
      alterations between the icv-STZ mouse and the 3xTg-AD mouse. We found that both
      mouse models showed increased exploratory activity as well as impaired learning
      and spatial memory. Both models also demonstrated neuroinflammation, altered
      synaptic proteins and insulin/IGF-1 (insulin-like growth factor-1) signaling, and
      increased hyperphosphorylated tau in the brain. The most prominent brain
      abnormality in the icv-STZ mouse was neuroinflammation, and in the 3xTg-AD mouse
      it was elevation of hyperphosphorylated tau. These observations demonstrate the
      behavioral and neuropathological similarities and differences between the icv-STZ
      mouse and the 3xTg-AD mouse models and will help guide future studies using these
      two mouse models for the development of AD drugs.

PMID- 23150173
TI  - Cucurbitacin D induces growth inhibition, cell cycle arrest, and apoptosis in
      human endometrial and ovarian cancer cells.
AB  - Cucurbitacin D, a newly isolated triterpenoid cucurbitacin, has been found to
      possess anticancer effects. The purpose of this study was to elucidate the
      effects of cucurbitacin D on human endometrial and ovarian cancer cells. Human
      endometrial and ovarian cancer cells were treated with various concentrations of
      cucurbitacin D, and its effects on cell growth, the cell cycle, apoptosis, and
      their related measurements were investigated in vitro. All endometrial and
      ovarian cancer cell lines were sensitive to the growth-inhibitory effect of
      cucurbitacin D. Cell cycle analysis indicated that their exposure to cucurbitacin
      D increased the proportion in the sub-G0/G1 phases and G2/M phases of the cell
      cycle. Induction of apoptosis was confirmed by annexin V staining of externalized
      phosphatidylserine and loss of the transmembrane potential of mitochondria. This
      induction occurred in concert with altered expression of genes related to cell
      growth, malignant phenotype, and apoptosis. Our results suggest that cucurbitacin
      D might be a new therapeutic option for the treatment of endometrial and ovarian
      cancers.

PMID- 23150174
TI  - CD133 induces tumour-initiating properties in HEK293 cells.
AB  - The pentaspan protein CD133 (Prominin-1) is part of the signature of tumour
      initiating cells for various cancer entities. The aim of the present study was to
      investigate the impact of ectopic CD133 expression on tumourigenic properties of
      otherwise CD133-negative, non-tumourigenic cells in vitro and in vivo. CD133 was
      stably transfected into human embryonic kidney 293 (HEK293) which was then sorted
      for the expression of CD133. The effects of CD133 on cell proliferation were
      assessed upon standard cell counting of sorted cells at various time points.
      Severe combined immunodeficient (SCID) mice (n = 30) were injected with HEK293
      CD133(high) and CD133(low) transfectants (5 * 10(3), 1 * 10(5), or 5 * 10(6)
      cells per injection). The expression of CD133, Ki67, CD44s, CD44v6, and EpCAM was
      analysed upon immunohistochemical staining of cryosections with specific
      antibodies. In vitro, ectopic expression of CD133 did influence neither cell
      proliferation nor cell cycle distribution of otherwise CD133-negative HEK293
      cells. However, CD133(high) cells generated tumours in vivo in SCID mice with at
      least 1,000-fold increased frequency compared to CD133(low) cells. Tumour load
      was also significantly increased in CD133(high) cells as compared to those
      tumours formed by high numbers of CD133(low) cells. Immunohistochemistry
      stainings disclosed no changes in Ki67, CD44s, CD44v6, or EpCAM once tumours were
      formed by either cell type. CD133 induces tumour-initiating properties in HEK293
      cells in vivo and is potentially involved in the regulation of tumourigenicity.
      Future research will aim at the elucidation of molecular mechanisms of CD133
      induced tumourigenicity.

PMID- 23150175
TI  - Expression of TWIST1, Snail, Slug, and NF-kappaB and methylation of the TWIST1
      promoter in mammary phyllodes tumor.
AB  - TWIST1, Slug, Snail, SIP1, and NF-kappaB are overexpressed in various tumors and
      associated with metastasis and poor prognosis. In this study, we examined their
      potential roles in phyllodes tumor (PT). The expression of TWIST1, Snail, Slug,
      SIP1, and NF-kappaB in benign (n = 103), borderline (n = 38), and malignant (n =
      38) PTs was examined by immunostaining. The methylation status of the TWIST1
      promoter was analyzed by methylation-specific PCR. We detected high expression
      levels of TWIST1 in 47.4 % of borderline/malignant PTs and 31.1 % of benign PTs,
      Slug in 64 % of borderline/malignant PTs and 62.1 % of benign PTs, epithelial
      SIP1 in 75.0 % of borderline/malignant PTs and 86.3 % of benign PTs, stromal SIP1
      in 35.5 % of borderline/malignant PTs and 22.3 % of benign PTs, and NF-kappaB in
      63.2 % of borderline/malignant PTs and 52.4 % of benign PTs. Snail expression was
      detected in all cases. A high expression of TWIST1 (p = 0.026) and TWIST1
      promoter methylation (p = 0.000) were significantly more frequent in
      borderline/malignant PTs than in benign PTs. Moreover, a high expression of at
      least four of the five antibodies was more commonly observed in
      borderline/malignant PTs than in benign PTs (p = 0.026). However, no relationship
      was found between the expression of TWIST1 or the other proteins examined and the
      clinical outcome. Our results suggest that a high expression of TWIST1 and
      related proteins plays a pivotal role in the malignant progression of PT.

PMID- 23150176
TI  - MiR-210 expression in tumor tissue and in vitro effects of its silencing in renal
      cell carcinoma.
AB  - Renal cell carcinoma (RCC) is the most common neoplasm of adult kidney accounting
      for about 3 % of adult malignancies. MicroRNAs (miRNAs) are a class of naturally
      occurring, short non-coding RNAs that regulate gene expression at the post
      transcriptional level. We determined global miRNA expression profiles of RCC and
      parallel renal parenchyma tissues by using quantitative reverse transcriptase
      polymerase chain reaction-based TaqMan low-density arrays. Afterward, we
      validated the difference in miR-210 expression levels on the larger group of RCC
      patients (35 RCC versus 10 non-tumorous parenchyma samples). Functional in vitro
      experiments were performed on ACHN and CAKI-2 RCC cell lines transfected with
      miRNA-210 inhibitor. Cell viability, apoptosis, cell cycle, scratch wound
      migration assay, and invasion assay (xCELLigence) were performed. We have
      identified original ccRCC-specific miRNA signature in clinical samples (73 miRNAs
      were significantly downregulated and five miRNAs upregulated (P < 0.003)).
      Increased expression levels of miR-210 in RCC tumor tissue were independently
      validated. We observed decreased viability of ACHN and CAKI-2 cells and
      accumulation of CAKI-2 in G2 phase of cell cycle after silencing of miR-210
      expression. Downregulation of miR-210 also reduced the migratory and invasive
      potential of ACHN metastatic RCC cells. Moreover, we showed downregulation of
      HIF1a protein in both cell lines after miR-210 silencing indicating participation
      of miR-210 in hypoxic processes of RCC not only through regulation of its target
      mRNAs but also by indirect regulation of HIF1a. To our knowledge, this is the
      first report to show miR-210 regulatory effects on cell migration, invasive
      potential, and HIF1a protein in RCC cells.

PMID- 23150177
TI  - Lack of mutational events of RAS genes in sporadic thyroid cancer but high risk
      associated with HRAS T81C single nucleotide polymorphism (case-control study).
AB  - High incidence of thyroid cancer worldwide indicates the importance of studying
      genetic alterations that lead to its carcinogenesis. Specific acquired RAS
      mutations have been found to predominate in different cancers, and HRAS T81C
      polymorphism has been determined to contribute the risk of various cancers,
      including thyroid cancer. We screened the exons 1 and 2 of RAS genes (HRAS, KRAS,
      and NRAS) in 60 consecutive thyroid tissue (tumor and adjacent normal) samples,
      and a case-control study was also conducted for HRAS T81C polymorphism in HRAS
      codon 27 using the polymerase chain reaction-restriction fragment length
      polymorphism to test the genotype distribution of 140 thyroid cancer patients in
      comparison with 170 cancer-free controls from a Kashmiri population. No mutation
      was found in any of the thyroid tumor tissue samples, but we frequently detected
      polymorphism at nucleotide 81 (T > C) in exon 1 of HRAS gene. In HRAS T81C SNP,
      frequencies of TT, TC, and CC genotypes among cases were 41.4, 38.6, and 20.0 %,
      while in controls genotype frequencies were 84.1, 11.7, and 4.2 %, respectively.
      A significant difference was observed in variant allele frequencies (TC + CC)
      between the cases and controls (58.6 vs. 16 %) with odds ratio = 7.4; confidence
      interval (CI) = 4.3-12.7 (P < 0.05). Interestingly, combined TC and CC genotype
      abundantly presented in follicular thyroid tumor (P < 0.05). Moreover, a
      significant association of the variant allele (TC + CC) was found with nonsmokers
      (P < 0.05). This study shows that although thyroid cancer is highly prevalent in
      this region, the mutational events for RAS genes do not seem to be involved.
      Contrary to this HRAS T81C SNP of HRAS gene moderately increases thyroid cancer
      risk with rare allele as a predictive marker for follicular tumors.

PMID- 23150178
TI  - Serum soluble MICB (sMICB) correlates with disease progression and survival in
      melanoma patients.
AB  - Recently, it was reported that soluble MICB (sMICB) may impair tumor
      immunogenicity by reducing natural killer group 2D ligand densities on malignant
      cells. The aim of this study was to elucidate the role of sMICB in melanoma
      patients. In the present study, we determined sMICB serum concentration in 125
      melanoma patients of different clinical stages of disease compared with 30
      healthy controls using an ELISA. The correlations between sMICB serum
      concentration and clinicopathologic variables were analyzed. sMICB serum level
      was significantly elevated (P < 0.0005) in melanoma patients (mean +/- SE = 8.60
      +/- 0.26 ng/ml) compared with healthy controls (mean +/- SE = 6.27 +/- 0.25
      ng/ml). Univariate analysis revealed a correlation of sMICB serum concentration
      with advanced stages of disease (P = 0.009). Only a slight increase in sMICB
      serum level (P = 0.057) could be observed in regard to the tumor burden. Patients
      undergoing current treatment with cytostatics (n = 18) revealed a strong increase
      in sMICB serum level (P < 0.0005), whereas treatment with IFN-alpha alone or
      combined with cytostatics (n = 19) showed no change in serum sMICB concentration.
      According to Kaplan-Meier analysis, elevated sMICB serum levels were associated
      with a poor overall and a progression-free survival. Multivariate analysis
      revealed sMICB serum concentration as an independent predictive factor for
      progression-free and overall survival. Our results show a prognostic relevance of
      serum sMICB in melanoma patients, indicating that the evaluation of sMICB serum
      level may be important for the selection of therapeutic strategies.

PMID- 23150179
TI  - TROP2 expression and its evolving role in tumor pathogenesis in systemic tumors.

PMID- 23150180
TI  - cAMP response element binding protein H mediates fenofibrate-induced suppression
      of hepatic lipogenesis.
AB  - AIMS/HYPOTHESIS: Fenofibrate is a drug used to treat hyperlipidaemia that works
      by inhibiting hepatic triacylglycerol synthesis. Sterol regulatory element
      binding protein-1c (SREBP-1c) is a major regulator of the expression of genes
      involved in hepatic triacylglycerol synthesis. In addition, endoplasmic reticulum
      (ER)-bound transcription factor families are involved in the control of various
      metabolic pathways. Here, we show a novel function for an ER-bound transcription
      factor, cAMP response element binding protein H (CREBH), in fenofibrate-mediated
      inhibition of hepatic lipogenesis. METHODS: The effects of fenofibrate and
      adenovirus-mediated Crebh (also known as Creb313) overexpression (Ad-Crebh) on
      hepatic SREBP-1c production and lipogenesis in vitro and in vivo were
      investigated. We also examined whether downregulation of endogenous hepatic Crebh
      by small interfering (si)RNA restores the fenofibrate effect on hepatic
      lipogenesis and SREBP-1c production. Finally, we examined the mechanism by which
      CREBH inhibits hepatic SREBP-1c production. RESULTS: Fasting and fenofibrate
      treatment induced CREBH production and decreased SREBP-1c levels. Indeed, Ad
      Crebh inhibited insulin- and liver X receptor agonist TO901317-induced Srebp-1c
      (also known as Srebf1) mRNA expression in cultured hepatocytes. Moreover,
      increased production of CREBH in the liver of mice following tail-vein injection
      of Ad-Crebh inhibited high-fat diet-induced hepatic steatosis through inhibition
      of Srebp-1c expression. The inhibition of endogenous Crebh expression by siRNA
      restored fenofibrate-induced suppression of Srebp-1c expression and hepatic lipid
      accumulation both in vitro and in vivo. CONCLUSIONS/INTERPRETATION: These results
      show that fenofibrate decreases hepatic lipid synthesis through induction of
      CREBH. This study suggests CREBH as a novel negative regulator of SREBP-1c
      production and hepatic lipogenesis.

PMID- 23150182
TI  - Self-sacrificial templating synthesis of porous quaternary Cu-Fe-Sn-S
      semiconductor nanotubes via microwave irradiation.
AB  - Uniform quaternary Cu(2)FeSnS(4) (CITS) nanotubes of outer diameter 400-800 nm
      and thickness 100-200 nm have been synthesized for the first time by a simple,
      rapid and easily scaled-up microwave nonaqueous route using benzyl alcohol as the
      microwave absorbing solvent. An interesting in situ generated one-dimensional
      Cu(Tu)Cl nanorod acting as a self-sacrificial template was crucial for the
      formation of the well-defined CITS nanotubes. Based on the designed time
      dependent experiments, a formation mechanism for the CITS nanotubes was also
      proposed. The resulting CITS nanotubes had a strong absorption in the visible
      region with a bandgap of 1.71 eV that was optimal for photovoltaic applications.
      Our study provided a microwave nonaqueous route generally applicable for the
      synthesis of quaternary chalcogenide semiconductor nanotubes.

PMID- 23150181
TI  - Circulating levels of the shed scavenger receptor sCD163 and association with
      outcome of critically ill patients.
AB  - PURPOSE: CD163, a scavenger receptor for haptoglobin-hemoglobin complexes, is
      almost exclusively expressed by monocytes and macrophages and is shedded (as
      sCD163) by inflammatory stimuli. Thus, high serum levels of sCD163 predicted
      mortality in certain inflammatory diseases. We investigated baseline levels, time
      course of sCD163 levels and CD163 gene expression in relation to mortality and
      clinical complications in a large heterogeneous cohort of critically ill
      patients. METHODS: In this pre-planned secondary analysis of two randomized
      clinical studies, critically ill patients (n = 1657) were randomized to
      "conventional" (insulin administered only for blood glucose levels above 215
      mg/dL) or "intensive" insulin therapy (glycemia maintained at 80-110 mg/dL) and
      compared with healthy controls (n = 112). RESULTS: Upon admission, critically ill
      patients had 1.6-fold higher sCD163 levels than controls (P < 0.0001). Long-stay
      patients (ICU stay >5 days), non-survivors and patients who developed liver
      dysfunction or kidney injury had higher baseline sCD163 levels. In multivariable
      analyses, elevated baseline sCD163 levels were independently associated with ICU
      mortality, liver dysfunction, and time to discharge from ICU and hospital. sCD163
      further increased during ICU stay in patients who developed organ dysfunction and
      in non-survivors. Avoiding hyperglycemia with insulin slightly reduced
      circulating sCD163 levels. Hepatic CD163 gene expression in patients was higher
      than in controls (P = 0.002) and correlated positively with sCD163 levels (P =
      0.345, P < 0.0001). CONCLUSIONS: This study hallmarks the association of elevated
      sCD163 with organ dysfunction and adverse outcome of critical illness and may
      point to the liver as a potential source.

PMID- 23150183
TI  - The high prevalence of vitamin D inadequacy and dress style of women in the sunny
      UAE.
AB  - In the UAE, 255 women with different dressing styles (veiled and non-veiled)
      underwent assay for vitamin D(3). The vitamin level was suboptimal in all groups
      including those dressed in Western style. The contribution of hypovitaminosis D
      to osteoporosis was less impressive compared to that of age factor. INTRODUCTION:
      Vitamin D deficiency is attributed to several causes including clothing styles
      that hinder exposure to sunlight. This work represents our experience of such
      issue and its relevance to osteoporosis. METHODS: Two hundred and fifty-five
      women either fully covered (96, group G1), covered but face and hands exposed
      (104, group G2) or dressed in Western style (55, group G3) all underwent
      immunoassay of 25(OH)D; 78 % of them were Middle Easterners and North Africans.
      The mean age was 44.8 +/- 14.6 years. RESULTS: In the entire cohort,
      hypovitaminosis D prevalence was found to be 90.5 % (mean of 25(OH)D, 19.3 +/-
      9.35 ng/ml). The prevalence was 90.5, 94 and 83 % (all p = not significant (NS)),
      with a mean value of 17.6 +/- 5.45, 16 +/- 5.23 and 18.6 +/- 6.18 ng/ml in the
      three groups, respectively. Significant differences in the mean value were
      observed between G1 vs. G2 (p = 0.04) and G2 vs. G3 (p = 0.01). Fifty-one women
      in G1 had longer adherence to their dressing habit than 68 in G2, yet the mean
      level of 25(OH)D was significantly lower in the latter (p = 0.008). Osteoporosis
      was found in 45/202 (22 %): 24.5, 22.5 and 14.5 % in the three groups,
      respectively (all p = NS). Patients with osteoporosis were significantly older
      than others with normal dual X-ray absorptiometry outcome. Values of serum
      calcium, phosphorus, alkaline phosphatase, mild to moderate secondary
      hyperparathyroidism and low 25(OH)D were comparable in the two groups.
      CONCLUSIONS: The pattern and longevity of dressing style should not be used as
      pretext for the hypovitaminosis D before other factors are being examined or
      considered.

PMID- 23150184
TI  - Heme oxygenase-1 attenuates epithelial-to-mesenchymal transition of human
      peritoneal mesothelial cells.
AB  - BACKGROUND: Epithelial-to-mesenchymal transition (EMT) of peritoneal mesothelial
      cells has been regarded as an early mechanism of peritoneal fibrosis. A
      substantial and rapidly growing literature indicates that HO-1 provides the
      provenance for pathways that can interrupt virtually all major mechanisms of
      tissue injury. The effects of HO-1 expression on EMT, which plays a critical role
      in the development of peritoneal membrane (PM) fibrosis, are unknown and its
      roles in peritoneal fibrosis has not been studied, yet. METHODS: A piece of human
      omentum obtained from consenting patients undergoing elective abdominal surgery
      was used for study. We treated the human peritoneal mesothelial cells (HPMCs)
      with high glucose solution and HO-1 inducer (hemin, 10 MUmol/L). To further
      investigate the pure effect of HO-1 on EMT of mesothelium, gene transfer of
      recombinant Adenovirus-harboring human HO-1 (Adv-HO-1 gene) to HPMCs was done.
      RESULTS: Exposure of HPMCs to HG solution resulted in an increase of the
      expression of mesenchymal markers such as alpha-smooth muscle actin (alpha-SMA)
      and was associated with a decrease in the expression of epithelial markers, E
      cadherin. HO-1 protein expression was decreased in the same situation. Treatment
      of HPMCs with HO-1 inducer, hemin showed a dosage-dependent amelioration of HG
      induced changes in markers of EMT with increase of expression of HO-1. Human HO-1
      gene transfection resulted in a significant increase in HO-1 expression and
      ameliorated HG-induced changes in expression of E-cadherin and alpha-SMA.
      CONCLUSION: Taken together, our results suggest that HO-1 has a critical role in
      the modulation of peritoneal fibrosis, and, more important, the suppression of
      EMT. This study is the first to show the beneficial effect of HO-1 on reversing
      EMT in MC.

PMID- 23150185
TI  - Association between high-molecular-weight adiponectin and bone mineral density in
      hemodialysis patients.
AB  - BACKGROUND: Chronic kidney disease-mineral and bone disorder is a regular
      complication seen in hemodialysis patients and leads to substantial increases in
      the fracture rate, morbidity, and mortality. Discovered a few years ago, several
      clinical studies have shown a negative correlation between adiponectin and bone
      mineral density (BMD) independently of confounding factors. The relationship
      between adiponectin and bone metabolism in hemodialysis patients has not been
      fully described yet. We conducted this study to investigate the relationship
      between serum adiponectin concentration and the BMD in hemodialysis patients.
      METHODS: We enrolled 92 hemodialysis patients who were receiving maintenance
      hemodialysis therapy at Towa Hospital. A peripheral blood sample was obtained,
      and standard biological data and the serum high-molecular-weight (HMW)
      adiponectin level were measured. BMD was assessed using dual-energy X-ray
      absorptiometry scans. RESULTS: In male hemodialysis patients, BMD was negatively
      related to age (r = -0.299, P = 0.012), duration of hemodialysis therapy (r = 
      0.31, P = 0.009), and log [HMW-adiponectin] (r = -0.31, P = 0.009) and positively
      related to body weight (r = 0.332, P = 0.004) and BMI (r = 0.297, P = 0.013). In
      female hemodialysis patients, BMD was negatively related to age (r = -0.499, P =
      0.018) and log [HMW-adiponectin] (r = -0.46, P = 0.030) and positively related to
      triglyceride (r = 0.491, P = 0.020). CONCLUSIONS: HMW adiponectin may affect bone
      metabolism in both male and female hemodialysis patients.

PMID- 23150186
TI  - Hereditary nephrogenic diabetes insipidus in Japanese patients: analysis of 78
      families and report of 22 new mutations in AVPR2 and AQP2.
AB  - BACKGROUND: Familial form of nephrogenic diabetes insipidus (NDI) is a rare
      hereditary disease caused by arginine vasopressin type 2 receptor (AVPR2) or
      water channel aquaporin 2 (AQP2) gene mutations. It is speculated that 90% of NDI
      families carry disease-causing mutations in AVPR2 and 10% carry the mutations in
      AQP2; however, these percentages have not been supported by actual data. It is
      also unknown whether these percentages vary in different ethnic groups. METHODS:
      Gene mutation analyses were performed for 78 Japanese NDI families. All exons and
      intron-exon boundaries of the AVPR2 and AQP2 genes were directly sequenced.
      RESULTS: A total of 62 families (79%) carried disease-causing mutations in AVPR2,
      while nine families (12%) carried mutations in AQP2. We identified 22 novel
      putatively disease-causing mutations (19 in AVPR2 and 3 in AQP2). Regarding
      AVPR2, 52 disease-causing mutations were identified. Among them, missense
      mutations were most common (54%), followed by deletion mutations. In the 64 women
      who had monoallelic disease-causing AVPR2 mutations, 16 (25%) had NDI symptoms,
      including 4 complete NDI subjects. Regarding AQP2, 9 disease-causing mutations
      were identified in nine families. Two missense mutations and one deletion
      mutation showed a recessive inheritance, while one missense mutation and five
      small deletion mutations in the C-terminus of AQP2 showed a dominant inheritance.
      CONCLUSIONS: Most Japanese NDI families carry disease-causing mutations in AVPR2
      and 12% carry mutations in AQP2. A total of 22 novel putatively disease-causing
      mutations were identified. The relatively high occurrence of symptomatic carriers
      of AVPR2 mutations needs attention.

PMID- 23150189
TI  - Power of metabolomics in diagnosis and biomarker discovery of hepatocellular
      carcinoma.
AB  - Hepatocellular carcinoma (HCC) is the commonest primary hepatic malignancy and
      the third most common cause of cancer-related death worldwide. Incidence remains
      highest in the developing world and is steadily increasing across the developed
      world. Current diagnostic modalities, of ultrasound and alpha-fetoprotein, are
      expensive and lack sensitivity in tumor detection. Because of its asymptomatic
      nature, HCC is usually diagnosed at late and advanced stages, for which there are
      no effective therapies. Thus, biomarkers for early detection and molecular
      targets for treating HCC are urgently needed. Emerging high-throughput
      metabolomics technologies have been widely applied, aiming at the discovery of
      candidate biomarkers for cancer staging, prediction of recurrence and prognosis,
      and treatment selection. Metabolic profiles, which are affected by many
      physiological and pathological processes, may provide further insight into the
      metabolic consequences of this severe liver disease. Small-molecule metabolites
      have an important role in biological systems and represent attractive candidates
      to understand HCC phenotypes. The power of metabolomics allows an unparalleled
      opportunity to query the molecular mechanisms of HCC. This technique-driven
      review aims to demystify the metabolomics pathway, while also illustrating the
      potential of this technique, with recent examples of its application in HCC.

PMID- 23150187
TI  - Platelet gel in cutaneous radiation dermatitis.
AB  - INTRODUCTION: Radiotherapy, alone or in combination with chemotherapy and/or
      surgery, is a fundamental and irreplaceable method of treating tumours.
      Nonetheless, although the technological advances made during recent years and the
      associated improvements in this type of treatment have reduced the incidence of
      complications, 5-15 % of patients still experience damage to the healthy tissues
      exposed to radiation. Cutaneous and mucosal lesions are severe collateral effects
      of radiotherapy that have an enormous impact on a patient's quality of life.
      Unfortunately, however, the efficacy of conventional treatments, while
      demonstrably useful in acute lesions, remains disputed in chronic cases.
      Nevertheless, numerous studies and clinical findings have demonstrated that
      topical, non-transfusional plasma-rich platelet gel is able to accelerate the
      regeneration and repair of tissues through the action of the various growth
      factors contained within the alpha granules of platelets. We therefore set out to
      evaluate the efficacy of autologous platelet gel, chosen for its limited cost and
      ease of preparation, in chronic cutaneous radiation dermatitis. METHODS: "Home
      made" platelet gel was produced by treating platelets with autologous thrombin.
      The safety of the product was ensured by microbiological tests. The autologous
      platelet gel was applied topically once a week, for a mean duration of 35 days,
      to chronic third- and fourth-degree (European Pressure Ulcer Advisory Panel
      classification and Common Terminology Criteria for Adverse Events score)
      cutaneous radiation dermatitis in a group of ten patients previously treated for
      moderate-to-high grade (histology G2-G3) limb sarcoma by tumour excision and post
      surgical radiotherapy (dose 50-64 Gy). The radiation dermatitis had appeared at
      different intervals after treatment and had all proved resistant to conventional
      treatments. RESULTS: The autologous platelet gel was found to be successful in
      seven out of the ten patients treated. The various phases of the healing process
      were observed in all cases. Platelet gel application was suspended in three
      patients: in one patient after one application due to tumour progression, in
      another patient after two applications due to development of distant metastases
      and in the third after six applications with only partial tissue response. At 5
      year follow-up, six of the seven successfully treated patients remained free of
      both disease and lesion, while the remaining patient, the eldest, had passed away
      in the interim due to extraneous causes. CONCLUSION: Platelet gel treatment could
      therefore be used to bring about healing in chronic cutaneous radiation
      dermatitis, lending itself to better patient compliance and a favourable
      cost/benefit ratio, due to a reduction in the number of medications and hospital
      visits required.

PMID- 23150188
TI  - The use of Ginkgo biloba for the prevention of chemotherapy-related cognitive
      dysfunction in women receiving adjuvant treatment for breast cancer, N00C9.
AB  - PURPOSE: Patients undergoing treatment for cancer often report problems with
      their cognitive function, which is an essential component of health-related
      quality of life. Pursuant to this, a two-arm randomized, placebo-controlled,
      double-blind, phase III clinical trial was conducted to evaluate Ginkgo biloba
      (EGB 761) for the prevention of chemotherapy-related cognitive dysfunction in
      patients with breast cancer. METHODS: Previously chemotherapy naive women about
      to receive adjuvant chemotherapy for breast cancer were randomized to receive 60
      mg of EGB 761 or a matching placebo twice daily. The study agent was to begin
      before their second cycle of chemotherapy and to be taken throughout chemotherapy
      and 1 month beyond completion. The primary measure for cognitive function was the
      High Sensitivity Cognitive Screen (HSCS), with a secondary measure being the
      Trail Making Tests (TMT) A and B. Subjective assessment of cognitive function was
      evaluated by the cognitive subscale of the Perceived Health Scale (PHS) and the
      Profile of Mood States (POMS). Data were collected at baseline and at intervals
      throughout and after chemotherapy, up to 24 months after completion of adjuvant
      treatment. The primary statistical analysis included normalized area under the
      curve (AUC) comparisons of the HSCS, between the arms. Secondary analyses
      included evaluation of the other measures of cognition as well as correlational
      analyses between self-report and cognitive testing. RESULTS: One hundred and
      sixty-six women provided evaluable data. There were no significant differences in
      AUC up to 12 months on the HSCS between arms at the end of chemotherapy or at any
      other time point after adjuvant treatment. There were also no significant
      differences in TMT A or B at any data point. Perceived cognitive functions, as
      measured by the PHS and confusion/bewilderment subscale of the POMS, were not
      different between arms at the end of chemotherapy. There was also little
      correlation between self-reported cognition and cognitive testing. No differences
      were observed in toxicities per Common Terminology Criteria for Adverse Events
      (CTCAE) assessment between Ginkgo biloba and placebo throughout the study;
      however, after chemotherapy, the placebo group reported worse nausea (p = .05).
      CONCLUSION: This study did not provide any support for the notion that Ginkgo
      biloba, at a dose of 60 mg twice a day, can help prevent cognitive changes from
      chemotherapy. These analyses do provide data to further support the low
      associations between patients' self-report of cognition and cognitive
      performance, based on more formal testing.

PMID- 23150191
TI  - A chiral phthalocyanine dimer with well-defined supramolecular symmetry based on
      pi-pi interactions.
AB  - Cooperation is the name of the game: The first example of a chiral phthalocyanine
      dimer with well-defined supramolecular weight and symmetry formed through
      cooperative multiple pi-pi interactions among nine pairs of aromatic moieties
      between two chiral phthalocyaninato zinc molecules has been clarified (see
      figure).

PMID- 23150190
TI  - Intrinsic properties of tumour cells have a key impact on the bystander effect
      mediated by genetically engineered mesenchymal stromal cells.
AB  - BACKGROUND: Engineered mesenchymal stromal cells (MSC) have been used in many
      preclinical studies of gene directed enzyme/prodrug therapy. We aimed to compare
      the efficacy of two most frequently used systems, as well as evaluate the extent
      of a bystander effect mediated by therapeutic MSC towards cell lines derived from
      different tumours. METHODS: Two approaches were compared: (i) herpes simplex
      virus thymidine kinase (TK)/ganciclovir (GCV) and (ii) yeast cytosine deaminase
      fused with uracil phosphoribosyltransferase (CD::UPRT)/5-fluorocytosine (5-FC).
      The cytotoxic effect mediated by therapeutic MSC was evaluated in direct co
      culture by a fluorimetric assay. The expression profile of tumour cells was
      analyzed by a quantitative polymerase chain reaction, and the ability of gap
      junctional intercellular communication (GJIC) was evaluated by a dye transfer
      assay. RESULTS: Both systems were effective only on glioblastoma cells (8-MG-BA).
      The CD::UPRT-MSC/5-FC system showed efficiency on melanoma A375 cells. We
      decreased the sensitivity of 8-MG-BA cells and A375 cells to the CD::UPRT-MSC/5
      FC system by pharmacological inhibition of thymidylate synthase, and we achieved
      a similar result in A375 cells by inhibition of thymidine phosphorylase. Although
      we demonstrated functional GJIC in A375 cells, TK-MSC were ineffective in
      mediating the bystander effect similarly to HeLa cells, which were also
      relatively resistant to CD::UPRT-MSC/5-FC treatment. TK-MSC/GCV treatment had a
      strong cytotoxic effect on MDA-MB-231 cells (breast carcinoma), whereas CD::UPRT
      MSC/5-FC treatment failed as a result of overexpression of the gene for ABCC11.
      Transfection of the MDA-MB-231 cell line with small interference RNA specific to
      ABCC11 led to a significantly increased sensitivity to the CD::UPRT-MSC/5-FC
      approach. CONCLUSIONS: GJIC, expression of enzymes involved in drug metabolism
      and ABC transporters correlate with the response of tumour cells to treatment by
      MSC-expressing prodrug-converting genes.

PMID- 23150192
TI  - Photocatalytic removal of soot: unravelling of the reaction mechanism by EPR and
      in situ FTIR spectroscopy.
AB  - Photocatalytic soot oxidation is studied on P25 TiO(2)  as an important model
      reaction for self-cleaning processes by means of electron paramagnetic resonance
      (EPR) and Fourier transform infrared (FTIR) spectroscopy. Contacting of carbon
      black with P25 leads on the one hand to a reduction of the local dioxygen
      concentration in the powder. On the other hand, the weakly adsorbed radicals on
      the carbon particles are likely to act as alternative traps for the
      photogenerated conduction-band electrons. We find furthermore that the presence
      of dioxygen and oxygen-related radicals is vital for the photocatalytic soot
      degradation. The complete oxidation of soot to CO(2)  is evidenced by in situ
      FTIR spectroscopy, no intermediate CO is detected during the photocatalytic
      process.

PMID- 23150193
TI  - Hybrid MRI/PET of the heart: a new complementary imaging technique for
      simultaneous acquisition of MRI and PET data.

PMID- 23150194
TI  - Reversal of aortic root inflammation after treatment of Wegener's granulomatosis.

PMID- 23150195
TI  - Extremely cold and hot temperatures increase the risk of ischaemic heart disease
      mortality: epidemiological evidence from China.
AB  - OBJECTIVE: To examine the effects of extremely cold and hot temperatures on
      ischaemic heart disease (IHD) mortality in five cities (Beijing, Tianjin,
      Shanghai, Wuhan and Guangzhou) in China; and to examine the time relationships
      between cold and hot temperatures and IHD mortality for each city. DESIGN: A
      negative binomial regression model combined with a distributed lag non-linear
      model was used to examine city-specific temperature effects on IHD mortality up
      to 20 lag days. A meta-analysis was used to pool the cold effects and hot effects
      across the five cities. PATIENTS: 16 559 IHD deaths were monitored by a sentinel
      surveillance system in five cities during 2004-2008. RESULTS: The relationships
      between temperature and IHD mortality were non-linear in all five cities. The
      minimum-mortality temperatures in northern cities were lower than in southern
      cities. In Beijing, Tianjin and Guangzhou, the effects of extremely cold
      temperatures were delayed, while Shanghai and Wuhan had immediate cold effects.
      The effects of extremely hot temperatures appeared immediately in all the cities
      except Wuhan. Meta-analysis showed that IHD mortality increased 48% at the 1st
      percentile of temperature (extremely cold temperature) compared with the 10th
      percentile, while IHD mortality increased 18% at the 99th percentile of
      temperature (extremely hot temperature) compared with the 90th percentile.
      CONCLUSIONS: Results indicate that both extremely cold and hot temperatures
      increase IHD mortality in China. Each city has its characteristics of heat
      effects on IHD mortality. The policy for response to climate change should
      consider local climate-IHD mortality relationships.

PMID- 23150196
TI  - Addressing commissioning difficulties is a priority for elderly prisoners.

PMID- 23150198
TI  - Latent-variable approaches to the Jamesian model of importance-weighted averages.
AB  - The individually importance-weighted average (IIWA) model posits that the
      contribution of specific areas of self-concept to global self-esteem varies
      systematically with the individual importance placed on each specific component.
      Although intuitively appealing, this model has weak empirical support; thus,
      within the framework of a substantive-methodological synergy, we propose a
      multiple-item latent approach to the IIWA model as applied to a range of self
      concept domains (physical, academic, spiritual self-concepts) and subdomains
      (appearance, math, verbal self-concepts) in young adolescents from two countries.
      Tests considering simultaneously the effects of self-concept domains on trait
      self-esteem did not support the IIWA model. On the contrary, support for a
      normative group importance model was found, in which importance varied as a
      function of domains but not individuals. Individuals differentially weight the
      various components of self-concept; however, the weights are largely determined
      by normative processes, so that little additional information is gained from
      individual weightings.

PMID- 23150197
TI  - Understanding the basis of a class of paradoxical mutations in AraC through
      simulations.
AB  - Most mutations at position 15 in the N-terminal arm of the regulatory protein
      AraC leave the protein incapable of responding to arabinose and inducing the
      proteins required for arabinose catabolism. Mutations at other positions of the
      arm do not have this behavior. Simple energetic analysis of the interactions
      between the arm and bound arabinose do not explain the uninducibility of AraC
      with mutations at position 15. Extensive molecular dynamics (MD) simulations,
      carried out largely on the Open Science Grid, were done of the wild-type protein
      with and without bound arabinose and of all possible mutations at position 15,
      many of which were constructed and measured for this work. Good correlation was
      found for deviation of arm position during the simulations and inducibility as
      measured in vivo of the same mutant proteins. Analysis of the MD trajectories
      revealed that preservation of the shape of the arm is critical to inducibility.
      To maintain the correct shape of the arm, the strengths of three interactions
      observed to be strong in simulations of the wild-type AraC protein need to be
      preserved. These interactions are between arabinose and residue 15, arabinose and
      residues 8-9, and residue 13 and residue 15. The latter interaction is notable
      because residues L9, Y13, F15, W95, and Y97 form a hydrophobic cluster which
      needs to be preserved for retention of the correct shape.

PMID- 23150199
TI  - When to use your head and when to use your heart: the differential value of
      perspective-taking versus empathy in competitive interactions.
AB  - Four studies explored whether perspective-taking and empathy would be
      differentially effective in mixed-motive competitions depending on whether the
      critical skills for success were more cognitively or emotionally based. Study 1
      demonstrated that individual differences in perspective-taking, but not empathy,
      predicted increased distributive and integrative performance in a multiple-round
      war game that required a clear understanding of an opponent's strategic
      intentions. Conversely, both measures and manipulations of empathy proved more
      advantageous than perspective-taking in a relationship-based coalition game that
      required identifying the strength of interpersonal connections (Studies 2-3).
      Study 4 established a key process: perspective-takers were more accurate in
      cognitive understanding of others, whereas empathy produced stronger accuracy in
      emotional understanding. Perspective-taking and empathy were each useful but in
      different types of competitive, mixed-motive situations-their success depended on
      the task-competency match. These results demonstrate when to use your head versus
      your heart to achieve the best outcomes for oneself.

PMID- 23150200
TI  - Detection of circulating tumor cells in peripheral blood of colorectal cancer
      patients without distant organ metastases.
AB  - PURPOSE: Recently, the detection of circulating tumor cells (CTCs) in peripheral
      blood has become an important tool for the non-invasive assessment of
      micrometastases and to predict clinical outcome. The objective of this study was
      to investigate if the presence of CTCs in peripheral blood influences the
      prognosis in colorectal cancer (CRC) patients without distant organ metastases.
      METHODS: The GCC mRNA and CK20 mRNA levels in peripheral blood and the serum
      levels of CEA of 92 CRC patients without distant organ metastasis were analyzed
      by quantitative RT-PCR and ELISA, respectively. Its associations with overall
      survival (OS) and disease-free survival (DFS) rates were analyzed. RESULTS:
      Univariate analyses showed that lower OS and DFS rates were significantly
      associated with GCC and CK20 mRNA levels, the presence of lymph node metastases,
      the presence of mesenteric root lymph node metastases, and the presence of tumor
      emboli in vessels (p < 0.05), but not with CEA levels. Multivariate analyses
      showed a significant association between 1) OS and GCC mRNA levels and
      differentiation types and 2) DFS and the presence of tumor emboli in the vessels.
      Kaplan-Meier curves showed that DFS was significantly associated with the
      presence of poorly differentiated cells, the presence of mesenteric root lymph
      node metastases having received prior chemotherapy, and the presence of tumor
      emboli in vessels. CONCLUSION: The detection of CTCs in peripheral blood may be
      useful for the prediction of clinical outcome in CRC patients without distant
      organ metastases.

PMID- 23150201
TI  - Haemophilia A associated with Down's syndrome.

PMID- 23150202
TI  - Oligoclonal reconstitution masquerading as myeloma relapse.

PMID- 23150203
TI  - ZnO dense nanowire array on a film structure in a single crystal domain texture
      for optical and photoelectrochemical applications.
AB  - A single crystal domain texture quality (a unique in-plane and out-of-plane
      crystalline orientation over a large area) ZnO nanostructure of a dense nanowire
      array on a thick film has been homogeneously synthesized on a-plane sapphire
      substrates over large areas through a one-step chemical vapor deposition (CVD)
      process. The growth mechanism is clarified: a single crystal [02(-)1] oriented
      ZnAl(2)O(4) buffer layer was formed at the ZnO film and the a-plane sapphire
      substrate interface via a diffusion reaction process during the CVD process,
      providing improved epitaxial conditions that enable the synthesis of the high
      crystalline quality ZnO nanowire array on a film structure. The high
      optoelectronic quality of the ZnO nanowire array on a film sample is evidenced by
      the free exitonic emissions in the low-temperature photoluminescence
      spectroscopy. A carrier density of ~10(17) cm(-3) with an n-type conductivity of
      the ZnO nanowire array on a film sample is obtained by electrochemical impedance
      analysis. Finally, the ZnO nanowire array on a film sample is demonstrated to be
      an ideal template for a further synthesis of a single crystal quality ZnO
      ZnGa(2)O(4) core-shell nanowire array on a film structure. The fabricated ZnO
      ZnGa(2)O(4) sample revealed an enhanced anticorrosive ability and
      photoelectrochemical performance when used as a photoanode in a
      photoelectrochemical water splitting application.

PMID- 23150204
TI  - Print-to-print: a facile multi-object micro-patterning technique.
AB  - In recent years, micropatterning techniques have gained increasing popularity
      from a broad range of engineering and biology communities for the promise to
      establish highly quantitative investigations on miniature biological objects
      (e.g., cells and bacteria) with spatially defined microenvironments. However,
      majority of the existing techniques rely on cleanroom-based microfabrication and
      cannot be easily extended to a regular biological laboratory. In this paper, we
      present a simple versatile printing-based method, referred to as Print-to-Print
      (P2P), to form multi-object micropatterns for potential biological applications,
      along with our recent efforts to deliver out-of-cleanroom microfabrication
      solutions to the general public (Zhao et al. 2009), (Xing et al. 2011), (Wang et
      al. 2009), (Pan and Wang 2011), (Zhao et al. 2011). The P2P method employs only a
      commercially available solid-phase printer and custom-made superhydrophobic
      films. The entire patterning process does not involve any thermal or chemical
      treatment. Moreover, the non-contact nature of droplet transferring and printing
      steps can be highly advantageous for sensitive biological uses. Using the P2P
      process, a minimal feature resolution of 229 +/- 17 MUm has been successfully
      demonstrated. In addition, this approach has been applied to form biological
      micropatterning on various substrates as well as multi-object co-patterns on the
      commonly used surfaces. Finally, the reusability of superhydrophobic substrates
      has also been illustrated.

PMID- 23150205
TI  - A micro blood sampling system for catheterized neonates and pediatrics in
      intensive care unit.
AB  - A new micro blood sampling system has been designed, fabricated, and
      characterized to reduce iatrogenic blood loss from the catheterized neonates and
      pediatrics in intensive care unit by providing micro-volume of blood to
      analytical biomedical microdevices which can do point-of-care testing for their
      critical care. The system can not only save enormous iatrogenic blood loss
      through 1 to 10 MUL of blood sampling and re-infusion of 1 to 5 mL of discard
      blood but also reduce the infection risk through the closed structure while
      satisfying the key criteria of the blood sampler. The sampled blood preserved its
      quality without rupturing of red blood cells verified by blood potassium
      concentrations of 3.86 +/- 0.07 mM on the sampled blood which is similar to 3.81
      +/- 0.04 mM measured from the blood which did not go through the system. The
      sampling volume among the sampling channels showed consistency with the relative
      standard deviation of 1.41 %. In addition to the micro blood sampling capability,
      the sampling system showed negligible sample cross-contamination. The analyte
      free samples collected after aspirating 7,500 times higher signal sample showed
      the same output signal as blank. The system was also demonstrated not to cause
      air-embolism by having no bubble generation during flushing procedure and the
      system was verified as leak-free since there was no fluid leakage under 30 times
      higher pressure than central venous pressure for 24 h.

PMID- 23150207
TI  - Fibrous nanostructures from the self-assembly of designed repeat protein modules.
AB  - Single-protein-chain superhelical filaments are obtained from monomeric repeat
      proteins by controlling the chemistry and solvent exposure at their terminal
      interfaces. The assembly was achieved in aqueous solution, at neutral pH value,
      and at room temperature. The building block was a recombinantly engineered
      designed tetratricopeptide repeat protein. Directed head-to-tail self-assembly
      was driven by genetically encoded orthogonal native chemical ligation.

PMID- 23150206
TI  - Serum vitamin D increases with weight loss in obese subjects 6 months after Roux
      en-Y gastric bypass.
AB  - BACKGROUND: Malabsorptive surgical procedures lead to deficiencies in fat-soluble
      vitamins. However, results concerning serum vitamin D (25OHD) after gastric
      bypass (GBP) are controversial. The aim of the study was to assess the influence
      of GBP on 25OHD and calcium metabolism. METHODS: Parameters of calcium metabolism
      were evaluated in 202 obese subjects before and 6 months after GBP. Thirty of
      them were matched for age, gender, weight, skin color, and season with 30
      subjects who underwent sleeve gastrectomy (SG). A multivitamin preparation that
      provides 200 to 500 IU vitamin D3 per day was systematically prescribed after
      surgery. RESULTS: In the 202 patients after GBP, serum 25OHD significantly
      increased from 13.4 +/- 9.1 to 22.8 +/- 11.3 ng/ml (p < 0.0001), whereas
      parathyroid hormone (PTH) did not change. Despite a decrease in calcium intake (p
      < 0.0001) and urinary calcium/creatinine ratio (p = 0.015), serum calcium
      increased after GBP (p < 0.0001). Preoperatively, 91 % of patients had 25OHD
      insufficiency (< 30 ng/ml), 80% deficiency (< 20 ng/ml), and 19% secondary
      hyperparathyroidism (> 65 pg/ml) vs. 76, 44, and 17%, respectively, following
      GBP. Serum 25OHD was negatively correlated with BMI at 6 months after GBP (R = 
      0.299, p < 0.0001). In the two groups of 30 subjects, serum 25OHD and PTH did not
      differ at 6 months after GBP or SG. CONCLUSIONS: At 6 months after GBP, serum
      25OHD significantly increased in subjects supplemented with multivitamins
      containing low doses of vitamin D. These data suggest that weight loss at 6
      months after surgery has a greater influence on vitamin D status than
      malabsorption induced by GBP.

PMID- 23150209
TI  - Metal ions do not play a direct role in the formation of carbon-carbon triple
      bonds during reduction of trihaloalkyls by Cr(II) or V(II).
AB  - Carbyne radicals: Reactions of trihaloalkyl compounds with Cr(2+) or V(2+) in
      aqueous solutions yield alkynes and other products. Stepwise halogen abstractions
      from the trihaloalkyls form alkyl carbyne triradicals in solution. These radicals
      undergo coupling reactions, producing triply bonded alkyne molecules (see
      scheme). This process is not metal-assisted and does not occur in the
      coordination sphere of the metal ions.

PMID- 23150208
TI  - Preexisting epithelial diversity in normal human livers: a tissue-tethered
      cytometric analysis in portal/periportal epithelial cells.
AB  - Routine light microscopy identifies two distinct epithelial cell populations in
      normal human livers: hepatocytes and biliary epithelial cells (BECs).
      Considerable epithelial diversity, however, arises during disease states when a
      variety of hepatocyte-BEC hybrid cells appear. This has been attributed to
      activation and differentiation of putative hepatic progenitor cells (HPC)
      residing in the canals of Hering and/or metaplasia of preexisting mature
      epithelial cells. A novel analytic approach consisting of multiplex labeling,
      high-resolution whole-slide imaging (WSI), and automated image analysis was used
      to determine if more complex epithelial cell phenotypes preexist in normal adult
      human livers, which might provide an alternative explanation for disease-induced
      epithelial diversity. "Virtually digested" WSI enabled quantitative cytometric
      analyses of individual cells displayed in a variety of formats (e.g.,
      scatterplots) while still tethered to the WSI and tissue structure. We employed
      biomarkers specifically associated with mature epithelial forms (HNF4alpha for
      hepatocytes, CK19 and HNF1beta for BEC) and explored for the presence of cells
      with hybrid biomarker phenotypes. The results showed abundant hybrid cells in
      portal bile duct BEC, canals of Hering, and immediate periportal hepatocytes.
      These bipotential cells likely serve as a reservoir for the epithelial diversity
      of ductular reactions, appearance of hepatocytes in bile ducts, and the rapid and
      fluid transition of BEC to hepatocytes, and vice versa. CONCLUSION: Novel imaging
      and computational tools enable increased information extraction from tissue
      samples and quantify the considerable preexistent hybrid epithelial diversity in
      normal human liver. This computationally enabled tissue analysis approach offers
      much broader potential beyond the results presented here.

PMID- 23150210
TI  - Synthesis and quantitative structure-activity relationships of selective BCRP
      inhibitors.
AB  - The breast cancer resistance protein (BCRP/ABCG2) is a member of the ABC
      transporter superfamily. This protein has a number of physiological functions,
      including protection of the human body from xenobiotics. The overexpression of
      BCRP in certain tumor cell lines causes cross-resistance against various drugs
      used in chemotherapeutic treatment. In a previous work we showed that a new class
      of compounds derived from XR9576 (tariquidar) selectively inhibits BCRP. In this
      work we synthesized more members of this class, with modification on the second
      and third aromatic rings. The inhibitory activities against BCRP and P-gp were
      assayed using a Hoechst 33342 assay for BCRP and a calcein AM assay for P-gp.
      Finally, quantitative structure-activity relationships for both aromatic rings
      were established. The results obtained show the importance of the electron
      density on the third aromatic ring, influenced by substituents, pointing to
      interactions with aromatic residues of the protein binding site. In the second
      aromatic ring the activity of compounds is influenced by the steric volume of the
      substituents.

PMID- 23150212
TI  - Editorial commentary: extended-spectrum beta-lactamase-producing escherichia coli
      in the united states: time to rethink empirical treatment for suspected E. coli
      infections?

PMID- 23150211
TI  - Community-associated extended-spectrum beta-lactamase-producing Escherichia coli
      infection in the United States.
AB  - Background. The occurrence of community-associated infections due to extended
      spectrum beta-lactamase (ESBL)-producing Escherichia coli has been recognized as
      a major clinical problem in Europe and other regions. Methods. We conducted a
      prospective observational study to examine the occurrence of community-associated
      infections due to ESBL-producing E. coli at centers in the United States. Five
      academic and community hospitals and their affiliated clinics participated in
      this study in 2009 and 2010. Sites of acquisition of the organisms (community
      associated or healthcare-associated), risk factors, and clinical outcome were
      investigated. Screening for the global epidemic sequence type (ST) 131 and
      determination of the ESBL types was conducted by polymerase chain reaction and
      sequencing. Results. Of the 291 patients infected or colonized with ESBL
      producing E. coli as outpatients or within 48 hours of hospitalization, 107
      (36.8%) had community-associated infection (81.5% of which represented urinary
      tract infection), while the remainder had healthcare-associated infection.
      Independent risk factors for healthcare-associated infection over community
      associated infection were the presence of cardiovascular disease, chronic renal
      failure, dementia, solid organ malignancy, and hospitalization within the
      previous 12 months. Of the community-associated infections, 54.2% were caused by
      the globally epidemic ST131 strain, and 91.3% of the isolates produced CTX-M-type
      ESBL. Conclusions. A substantial portion of community-onset, ESBL-producing E.
      coli infections now occur among patients without discernible healthcare
      associated risk factors in the United States. This epidemiologic shift has
      implications for the empiric management of community-associated infection when
      involvement of E. coli is suspected.

PMID- 23150214
TI  - Structure-from-motion: dissociating perception, neural persistence, and sensory
      memory of illusory depth and illusory rotation.
AB  - In the structure-from-motion paradigm, physical motion on a screen produces the
      vivid illusion of an object rotating in depth. Here, we show how to dissociate
      illusory depth and illusory rotation in a structure-from-motion stimulus using a
      rotationally asymmetric shape and reversals of physical motion. Reversals of
      physical motion create a conflict between the original illusory states and the
      new physical motion: Either illusory depth remains constant and illusory rotation
      reverses, or illusory rotation stays the same and illusory depth reverses. When
      physical motion reverses after the interruption in presentation, we find that
      illusory rotation tends to remain constant for long blank durations (T (blank) >=
      0.5 s), but illusory depth is stabilized if interruptions are short (T (blank) <=
      0.1 s). The stability of illusory depth over brief interruptions is consistent
      with the effect of neural persistence. When this is curtailed using a mask,
      stability of ambiguous vision (for either illusory depth or illusory rotation) is
      disrupted. We also examined the selectivity of the neural persistence of illusory
      depth. We found that it relies on a static representation of an interpolated
      illusory object, since changes to low-level display properties had little
      detrimental effect. We discuss our findings with respect to other types of
      history dependence in multistable displays (sensory stabilization memory, neural
      fatigue, etc.). Our results suggest that when brief interruptions are used during
      the presentation of multistable displays, switches in perception are likely to
      rely on the same neural mechanisms as spontaneous switches, rather than switches
      due to the initial percept choice at the stimulus onset.

PMID- 23150213
TI  - The clinical relevance of plasma protein binding changes.
AB  - Controversy reigns as to how protein binding changes alter the time course of
      unbound drug concentrations in patients. Given that the unbound concentration is
      responsible for drug efficacy and potential drug toxicity, this area is of
      significant interest to clinicians and academics worldwide. The present
      uncertainty means that many questions relating to this area exist, including "How
      important is protein binding?", "Is protein binding always constant?", "Do pH and
      temperature changes alter binding?" and "How do protein binding changes affect
      dosing requirements?". In this paper, we seek to address these questions and
      consider the data associated with altered pharmacokinetics in the presence of
      changes in protein binding and the clinical consequences that these may have on
      therapy, using examples from the critical care area. The published literature
      consistently indicates that a change in the protein binding and unbound
      concentrations of some drugs are common in certain specific patient groups such
      as the critically ill. Changes in pharmacokinetic parameters, including clearance
      and apparent volume of distribution (V(d)), may be dramatic. Drugs with high
      protein binding, high intrinsic clearance (e.g. clearance by glomerular
      filtration) and where dosing is not titrated to effect are most likely to be
      affected in a clinical context. Drugs such as highly protein bound antibacterials
      with multiple half-lives within a dosing interval and that have some level of
      renal clearance, such as ertapenem, teicoplanin, ceftriaxone and flucloxacillin,
      are commonly affected. In response to these challenges, clinicians need to adapt
      dosing regimens rationally based on the pharmacokinetic/pharmacodynamic
      characteristics of the drug. We propose that further pharmacokinetic modelling
      based research is required to enable the design of robust dosing regimens for
      drugs affected by altered protein binding.

PMID- 23150215
TI  - The effect of vertical and horizontal symmetry on memory for tactile patterns in
      late blind individuals.
AB  - Visual stimuli that exhibit vertical symmetry are easier to remember than stimuli
      symmetric along other axes, an advantage that extends to the haptic modality as
      well. Critically, the vertical symmetry memory advantage has not been found in
      early blind individuals, despite their overall superior memory, as compared with
      sighted individuals, and the presence of an overall advantage for identifying
      symmetric over asymmetric patterns. The absence of the vertical axis memory
      advantage in the early blind may depend on their total lack of visual experience
      or on the effect of prolonged visual deprivation. To disentangle this issue, in
      this study, we measured the ability of late blind individuals to remember tactile
      spatial patterns that were either vertically or horizontally symmetric or
      asymmetric. Late blind participants showed better memory performance for
      symmetric patterns. An additional advantage for the vertical axis of symmetry
      over the horizontal one was reported, but only for patterns presented in the
      frontal plane. In the horizontal plane, no difference was observed between
      vertical and horizontal symmetric patterns, due to the latter being recalled
      particularly well. These results are discussed in terms of the influence of the
      spatial reference frame adopted during exploration. Overall, our data suggest
      that prior visual experience is sufficient to drive the vertical symmetry memory
      advantage, at least when an external reference frame based on geocentric cues
      (i.e., gravity) is adopted.

PMID- 23150216
TI  - In vitro binding of a radio-labeled positive allosteric modulator for
      metabotropic glutamate receptor subtype 5.
AB  - The positive allosteric modulator (PAM) binding site for metabotropic glutamate
      receptor subtype 5 (mGlu(5)) lacks a readily available radio-labeled tracer
      fordetailed structure-activity studies. This communication describes a selective
      mGlu(5) compound, 7-methyl-2-(4-(pyridin-2-yloxy)benzyl)-5-(pyridin-3
      yl)isoindolin-1-one (PBPyl) that binds with high affinity to human mGlu(5) and
      exhibits functional PAM activity. Analysis of PBPyl by FLIPR revealed an EC(50)
      of 87 nM with an 89% effect in transfected HEK293 cells and an EC(50) of 81 nM
      with a 42% effect in rat primary neurons. PBPyl exhibited 5-fold higher
      functional selectivity for mGlu(5) in a full mGlu receptor panel. Unlabeled PBPyl
      was tested for specific binding using a liquid chromatography mass spectrometry
      (LC/MS/MS)-based filtration binding assay and exhibited 40% specific binding in
      recombinant membranes, a value higher than any candidate compound tested. In
      competition binding studies with [(3)H]MPEP, the mGlu(5) receptor negative
      allosteric modulator (NAM), PBPyl exhibited a k(i) value of 34 nM. PBPyl also
      displaced [(3)H]ABP688, a mGluR(5) receptor NAM, in tissue sections from mouse
      and rat brain using autoradiography. Areas of specific binding included the
      frontal cortex, striatum and nucleus accumbens. PBPyl was radiolabeled to a
      specific activity of 15 Ci/mmol and tested for specific binding in a filter plate
      format. In recombinant mGlu(5b) membranes, [(3)H] PBPyl exhibited saturable
      binding with a K(d) value of 18.6 nM. In competition binding experiments, [(3)H]
      PBPyl was displaced by high affinity mGlu(5) positive and negative modulators.
      Further tests showed that PBPyl displays less than optimal characteristics as an
      in vivo tool, including a high volume of distribution and ClogP, making it more
      suitable as an in vitro compound. However, as a first report of direct binding of
      an mGlu(5) receptor PAM, this study offers value toward the development of novel
      PET imaging agents for this important therapeutic target.

PMID- 23150217
TI  - Comments on "SEOM guidelines for endometrial cancer".

PMID- 23150218
TI  - Management and outcome of ovarian malignancy complicating pregnancy: an analysis
      of 41 cases and review of the literature.
AB  - OBJECTIVE: The aims of this study are to summarize our experience of managing
      ovarian malignancy complicating pregnancy, to discuss the maternal and fetal
      outcomes, and to review the literature concerned. METHODS: Forty-one patients
      with ovarian malignancies complicating pregnancy at Peking Union Medical College
      Hospital between 1990 and 2012 were retrospectively reviewed. RESULTS: Of the 41
      patients, malignancies included epithelial ovarian cancers (13/41, 31.7 %),
      epithelial borderline ovarian tumors (12/41, 29.3 %), ovarian malignant germ cell
      tumors (10/41, 24.4 %), sexcord stromal tumors (3/41, 7.3 %), metastatic ovarian
      tumors (2/41, 4.9 %), and primary ovarian choriocarcinoma (1/41, 2.4 %). The
      median overall survival was 30 months (range 3-165), with an overall mortality
      rate of 24.4 %. The pregnancy outcomes included termination in the first
      trimester (8/41, 19.5 %), full-term vaginal delivery (7/41, 17.0 %), full-term
      cesarean section (17/41, 41.5 %), and therapeutic cesarean section for premature
      birth (9/41, 22.0 %). One preterm newborn died, and the remaining 32 survived in
      healthy status. All patients underwent surgery, and those who deliberately
      delayed radical surgery had gloomy prognosis. Two patients received chemotherapy
      during pregnancy, and 24 patients started chemotherapy after pregnancy
      termination. CONCLUSIONS: Management priority should be given to the malignancy
      of ovarian tumors at any stage of pregnancy. Surgical intervention is the main
      treatment modality, and delaying of radical surgery is not recommended for
      patients with suspicion of high malignancy. Early diagnosis and appropriate
      treatment could offer satisfactory prognosis.

PMID- 23150219
TI  - CHEK2 c.1100delC mutation among non-BRCA1/2 Spanish hereditary breast cancer
      families.

PMID- 23150220
TI  - Depicting the evolving scenario of translational-guided drug development.

PMID- 23150221
TI  - Surface segregation in TiO2-based nanocomposite thin films.
AB  - The morphology of nanocomposites plays a pivotal role in understanding their
      functionality and determines their capabilities for applications. The use of
      nanocomposite coatings requires a study of the size effects on their functional
      properties. Noble metal nanoparticles are promising candidates for nanocomposite
      thin film applications due to their antibacterial, plasmonic and photocatalytic
      properties. In this contribution, the morphology of Ag-TiO(2) and Au-TiO(2)
      nanocomposite thin films has been investigated experimentally using electron
      tomography in transmission electron microscopy in combination with UV/vis
      spectroscopy. Based on the additional 3D information obtained from tomography, we
      propose a two-step model towards the observed bimodal particle size in these
      nanocomposite thin films prepared by co-sputtering from two different sources.
      Furthermore, we show that the optical properties exhibit a well-defined relation
      with the morphology of the nanocomposite thin films.  The present investigations
      demonstrate the potential of electron tomography for revealing the complex
      structure and formation processes of functional nanocomposites.

PMID- 23150222
TI  - Combination of phage display and molecular grafting generates highly specific
      tumor-targeting miniproteins.
AB  - Frankenstein's peptide: the grafting of the binding domain from miniprotein Min
      23 into the sunflower trypsin inhibitor (SFTI-I) peptide scaffold preserved its
      in vitro and in vivo binding specificity and proteolytic stability. The
      combination of these peptides was shown to be tumor-specific with a good binding
      affinity for delta-like ligand 4 (Dll4) protein. The use of SFTI-I as a peptide
      scaffold is ideal for hit-to-lead development.

PMID- 23150223
TI  - John Bell's conflict of interest.

PMID- 23150225
TI  - Direct sp3 C-H amination of nitrogen-containing benzoheterocycles mediated by
      visible-light-photoredox catalysts.
AB  - Visible-light-mediated direct sp(3) C-H amination of benzocyclic amines via alpha
      aminoalkyl radicals by using photoredox catalysts is described here. The obtained
      N,N-acetals were also successfully applied for carbon-carbon bond forming
      reactions with carbon nucleophiles. The procedure is suitable for a late-stage
      modification of C-H bonds to C-C bonds.

PMID- 23150224
TI  - Chimeric hepatitis B virus/hepatitis C virus envelope proteins elicit broadly
      neutralizing antibodies and constitute a potential bivalent prophylactic vaccine.
AB  - The development of a prophylactic vaccine against hepatitis C virus (HCV) has
      become an important medical priority, because 3-4 million new HCV infections are
      thought to occur each year worldwide. Hepatitis B virus (HBV) is another major
      human pathogen, but infections with this virus can be prevented with a safe,
      efficient vaccine, based on the remarkable ability of the envelope protein (S) of
      this virus to self-assemble into highly immunogenic subviral particles. Chimeric
      HBV-HCV envelope proteins in which the N-terminal transmembrane domain of S was
      replaced with the transmembrane domain of the HCV envelope proteins (E1 or E2)
      were efficiently coassembled with the wild-type HBV S protein into subviral
      particles. These chimeric particles presented the full-length E1 and E2 proteins
      from a genotype 1a virus in an appropriate conformation for formation of the E1
      E2 heterodimer. Produced in stably transduced Chinese hamster ovary cells and
      used to immunize New Zealand rabbits, these particles induced a strong specific
      antibody (Ab) response against the HCV and HBV envelope proteins in immunized
      animals. Sera containing anti-E1 or anti-E2 Abs elicited by these particles
      neutralized infections with HCV pseudoparticles and cell-cultured viruses derived
      from different heterologous 1a, 1b, 2a, and 3 strains. Moreover, the anti
      hepatitis B surface response induced by these chimeric particles was equivalent
      to the response induced by a commercial HBV vaccine. CONCLUSIONS: Our results
      provide support for approaches based on the development of bivalent HBV-HCV
      prophylactic vaccine candidates potentially able to prevent initial infection
      with either of these two hepatotropic viruses.

PMID- 23150226
TI  - Reduction of helical content by insertion of a disulfide bond leads to an
      antimicrobial peptide with decreased hemolytic activity.
AB  - CAPs off to the S-S bond: Application of a strategy involving the introduction of
      intramolecular disulfide bonds to amphipathic cationic antimicrobial peptides
      (CAPs) led to decreased alpha-helicity and hydrophobicity. The mutant peptides
      were observed to have significantly increased (250-fold) minimum hemolytic
      concentrations while maintaining MIC values against E. coli, affording more
      therapeutically selective CAPs.

PMID- 23150227
TI  - Perspectives: Professionalism and cardio-thoracic surgery.

PMID- 23150228
TI  - Mortality and morbidity in extremely low birth weight (ELBW) infants in a
      neonatal intensive care unit.
AB  - OBJECTIVE: To determine the morbidity and mortality in ELBW babies till discharge
      from a Neonatal Intensive Care Unit (NICU). METHODS: This study was a prospective
      observational study conducted in a 40 bed well equipped level III care NICU
      between 01.12.2006 and 30.04.2008. All ELBW babies admitted during this period
      were assessed for morbidities and interventions required during NICU stay and for
      their outcome like survival or death. RESULTS: The survival rate of 87 ELBW
      babies admitted during this period was 56.1 %. Pulmonary hemorrhage was the
      commonest cause of death (25 %) followed by respiratory distress syndrome (22.5
      %), intraventricular hemorrhage (22.5 %) and sepsis (20 %). Significantly higher
      number of non-survivors were <750 g at birth (p = 0.0001) and <28 wk gestation (p
      = 0.0001). Small for gestational babies had better chances of survival compared
      to those appropriate for gestational age (p = 0.005). RDS (67.8 %), probable
      sepsis (62.1 %) and hyperbilirubinemia (59.8 %) were the most frequent
      morbidities. Conventional ventilation (72.4 %) and nasal CPAP(48.3 %) were the
      commonest respiratory interventions. Surfactant replacement therapy was required
      in 47.1 % babies. CONCLUSIONS: ELBW babies have a major contribution to mortality
      in a NICU. Babies with birth weight <750 g and gestation <28 wk have poor
      survival. RDS, pulmonary hemorrhage, IVH and sepsis are the common causes of
      death while RDS, sepsis and hyperbilirubinemia are the most common morbidities.

PMID- 23150229
TI  - Adolescents living with HIV in India - the clock is ticking.
AB  - The term "Adolescence" literally means "to emerge" or "to attain identity" and is
      essentially the period of rapid physical and psychological development starting
      from the onset of puberty to complete growth. All adolescents go through a myriad
      of physical, psychological, neurobehavioural, hormonal and social developmental
      changes. Given the social taboos often surrounding puberty, the lives of millions
      of adolescents worldwide are at risk because they do not have the information,
      skills, health services and support they need to go through the enormous, rapid
      changes that adolescence brings. A HIV infected adolescent particularly presents
      enormous challenges in the current cultural and social context of India. The
      distinct groups of adolescents in the context of HIV are those who were infected
      at birth and survived and those who became infected during adolescence. Risk
      factors and situations for adolescents contracting HIV infection are life on
      streets, lack of adult love/care and support, extreme poverty, child trafficking,
      migrant population, exploitation in terms of sex and labor. HIV-infected
      adolescents with long standing HIV infection often face considerable physical
      challenges - delayed growth and development, late puberty, stunting/wasting,
      malnutrition, etc. Added to this are many other challenges related mainly to
      disclosure of HIV status, developmental delay, and transition from pediatric to
      adult care, including the choice of appropriate treatment regimens and adherence.
      Psychological and social factors deeply impact the ability to deal with the
      illness and must be addressed at all levels to encourage and support this
      vulnerable group.

PMID- 23150230
TI  - De novo design, synthesis and characterisation of MP3, a new catalytic four-helix
      bundle hemeprotein.
AB  - A new artificial metalloenzyme, MP3 (MiniPeroxidase 3), designed by combining the
      excellent structural properties of four-helix bundle protein scaffolds with the
      activity of natural peroxidases, was synthesised and characterised. This new
      hemeprotein model was developed by covalently linking the deuteroporphyrin to two
      peptide chains of different compositions to obtain an asymmetric helix-loop
      helix/heme/helix-loop-helix sandwich arrangement, characterised by 1) a His
      residue on one chain that acts as an axial ligand to the iron ion; 2) a vacant
      distal site that is able to accommodate exogenous ligands or substrates; and 3)
      an Arg residue in the distal site that should assist in hydrogen peroxide
      activation to give an HRP-like catalytic process. MP3 was synthesised and
      characterised as its iron complex. CD measurements revealed the high helix
      forming propensity of the peptide, confirming the appropriateness of the model
      procedure; UV/Vis, MCD and EPR experiments gave insights into the coordination
      geometry and the spin state of the metal. Kinetic experiments showed that Fe(III)
      MP3 possesses peroxidase-like activity comparable to R38A-hHRP, highlighting the
      possibility of mimicking the functional features of natural enzymes. The
      synergistic application of de novo design methods, synthetic procedures, and
      spectroscopic characterisation, described herein, demonstrates a method by which
      to implement and optimise catalytic activity for an enzyme mimetic.

PMID- 23150231
TI  - Chemical probes for drug-resistance assessment by binding competition (RABC):
      oseltamivir susceptibility evaluation.
AB  - The wizard of OS (resistance): the binding difference of neuraminidase inhibitors
      (zanamivir versus oseltamivir (OS)) was used to establish an assay to identify
      the influenza subtypes that are resistant to OS but still sensitive to zanamivir.
      This assay used a zanamivir-biotin conjugate to determine the OS susceptibility
      of a wide range of influenza viruses and over 200 clinical isolates.

PMID- 23150233
TI  - A facile one-pot synthesis of layered protonated titanate nanosheets loaded with
      silver nanoparticles with enhanced visible-light photocatalytic performance.
AB  - Layered protonated titanate nanosheets (LPTNs) loaded with silver nanoparticles
      are prepared by a simple one-pot hydrothermal route in silver-ammonia solution.
      The as-synthesized Ag-loaded LPTNs possess large specific surface area. The Ag
      nanoparticles are highly dispersed on the surface of the LPTNs. They have
      negligible effects on the crystal structure, crystallinity, and surface area of
      the LPTNs but result in considerable enhancement of visible-light absorption and
      in a red-shift of the band gap for the LPTNs. The Ag-loaded LPTNs show enhanced
      photocatalytic activity for both liquid- and gas-phase reactions under visible
      light irradiation. Moreover, the photocatalytic activity first increases
      gradually with increasing Ag loading content, and then decreases after maximizing
      at an optimal Ag content. At the Ag loading content of 2.87 mol% and 1.57 mol%,
      the Ag-loaded LPTNs exhibit the highest visible-light photocatalytic activity for
      degradation of rhodamine B in water and mineralization of benzene in air,
      respectively. An alternative possible mechanism for the enhancement of the
      visible-light photocatalytic activity is also proposed.

PMID- 23150232
TI  - Increased susceptibility of natural killer T-cell-deficient mice to acetaminophen
      induced liver injury.
AB  - Acetaminophen (APAP) overdose causes severe, fulminant liver injury. The
      underlying mechanism of APAP-induced liver injury (AILI), studied by a murine
      model, displays similar characteristics of injury as those observed in patients.
      Previous studies suggest that aside from APAP-induced direct damage to
      hepatocytes, the hepatic innate immune system is activated and may contribute to
      the overall pathogenesis of AILI. The current study employed the use of two
      murine natural killer (NK) cells with T-cell receptor (NKT) cell knockout models
      (CD1d(-/-) and Jalpha18(-/-) ) to elucidate the specific role of NKT cells in
      AILI. Compared to wild-type (WT) mice, NKT cell-deficient mice were more
      susceptible to AILI, as indicated by higher serum alanine transaminase levels and
      mortality. Increased levels of cytochrome P450 2E1 (CYP2E1) protein expression
      and activities, which resulted in increased APAP protein adduct formation, were
      observed in livers of APAP-treated NKT cell-deficient mice, compared to WT mice.
      Compared to WT mice, starvation of NKT cell-deficient mice induced a higher
      increase of ketone bodies, which up-regulate CYP2E1 through protein
      stabilization. CONCLUSION: Our data revealed a novel role of NKT cells in
      regulating responses to starvation-induced metabolic stress. Elevated ketone body
      production in NKT cell-deficient mice resulted in increased CYP2E1-mediated APAP
      biotransformation and susceptibility to AILI.

PMID- 23150234
TI  - An electronic diary study of the effects of patient avoidance and partner social
      constraints on patient momentary affect in metastatic breast cancer.
AB  - BACKGROUND: Metastatic breast cancer patients experience significance distress.
      Although talking with close others about cancer-related concerns may help to
      alleviate distress, patients often avoid such discussions, and their partners can
      engage in social constraints that may limit subsequent patient disclosures and
      exacerbate distress. PURPOSE: We examined how partner constraints unfold, how
      they influence patient affect, and whether they exacerbate patient avoidance of
      cancer-related disclosures. METHODS: Fifty-four patients and 48 of their partners
      completed electronic diary assessments for 14 days. RESULTS: Partners' social
      constraints carried over from one day to the next, but patients' avoidance of
      discussing cancer-related concerns did not. When partners engaged in more social
      constraints one day, patients reported greater negative affect the following day
      (p < 0.05). CONCLUSION: Findings suggest a temporal link between partner
      constraints and patient momentary affect. Helping partners to become aware of
      their constraining behaviors and teaching them skills to overcome this may
      facilitate patient adjustment to metastatic breast cancer.

PMID- 23150235
TI  - Spectroscopic evidence for the structure directing role of the solvent in the
      synthesis of two iron carboxylates.
AB  - Crystal engineering: The synthesis of the known compounds MIL-100(Fe) and MIL
      45(Fe) is characterized by spectroscopy. The products are obtained under
      identical conditions by varying the solvent from pure water to a mixture of water
      and acetone. The starting solution, the gel, and the final reaction product were
      characterized by X-ray absorption spectroscopy (see picture).

PMID- 23150236
TI  - Targeting androgen receptor in bone marrow mesenchymal stem cells leads to better
      transplantation therapy efficacy in liver cirrhosis.
AB  - Transplantation of bone marrow mesenchymal stem cells (BM-MSCs) has been
      considered as an alternative therapy, replacing liver transplantation in clinical
      trials, to treat liver cirrhosis, an irreversible disease that may eventually
      lead to liver cancer development. However, low survival rate of the BM-MSCs
      leading to unsatisfactory efficacy remains a major concern. Gender differences
      have been suggested in BM-MSCs therapeutic application, but the effect of the
      androgen receptor (AR), a key factor in male sexual phenotype, in this
      application is not clear. Using two liver cirrhosis mouse models induced by CCl4
      or thioacetamide, we showed that targeting AR in the BM-MSCs improved their self
      renewal and migration potentials and increased paracrine effects to exert anti
      inflammatory and anti-fibrotic actions to enhance liver repair. Mechanism
      dissection studies suggested that knocking out AR in BM-MSCs led to improved self
      renewal and migration by alteration of the signaling of epidermal growth factor
      receptor and matrix metalloproteinase 9 and resulted in suppression of
      infiltrating macrophages and hepatic stellate cell activation through modulation
      of interleukin (IL)1R/IL1Ra signaling. Therapeutic approaches using either
      AR/small interfering RNA or the AR degradation enhancer, ASC-J9, to target AR in
      BM-MSCs all led to increased efficacy for liver repair. CONCLUSION: Targeting AR,
      a key factor in male sexual phenotype, in BM-MSCs improves transplantation
      therapeutic efficacy for treating liver fibrosis.

PMID- 23150237
TI  - Lanthanide(III) complexes of bis-semicarbazone and bis-imine-substituted
      phenanthroline ligands: solid-state structures, photophysical properties, and
      anion sensing.
AB  - Phenanthroline-based hexadentate ligands L(1) and L(2) bearing two achiral
      semicarbazone or two chiral imine moieties as well as the respective mononuclear
      complexes incorporating various lanthanide ions, such as La(III), Eu(III),
      Tb(III), Lu(III), and Y(III) metal ions, were synthesized, and the crystal
      structures of [ML(1)Cl(3)] (M=La(III), Eu(III), Tb(III), Lu(III), or Y(III))
      complexes were determined. Solvent or water molecules act as coligands for the
      rare-earth metals in addition to halide anions. The big Ln(III) ion exhibits a
      coordination number (CN) of 10, whereas the corresponding Eu(III), Tb(III),
      Lu(III), and Y(III) centers with smaller ionic radii show CN=9. Complexes of
      L(2), namely [ML(2)Cl(3)] (M=Eu(III), Tb(III), Lu(III), or Y(III)) ions could
      also be prepared. Only the complex of Eu(III) showed red luminescence, whereas
      all the others were nonluminescent. The emission properties of the Eu derivative
      can be applied as a photophysical signal for sensing various anions. The addition
      of phosphate anions leads to a unique change in the luminescence behavior. As a
      case study, the quenching behavior of adenosine-5'-triphosphate (ATP) was
      investigated at physiological pH value in an aqueous solvent. A specificity of
      the sensor for ATP relative to adenosine-5'-diphosphate (ADP) and adenosine-5'
      monophosphate (AMP) was found. (31)P NMR spectroscopic studies revealed the
      formation of a [EuL(2)(ATP)] coordination species.

PMID- 23150239
TI  - Corticosteroids and open-angle glaucoma in the elderly: a population-based cohort
      study.
AB  - BACKGROUND: It is largely unknown if corticosteroid-induced open-angle glaucoma
      (OAG) is an entity that is limited to a few susceptible individuals or whether it
      contributes significantly to the overall population burden of OAG. OBJECTIVE: The
      aim of this study was to determine whether there is an association between
      corticosteroid use and the incidence of OAG in the general elderly population.
      METHODS: A prospective population-based cohort study was conducted in a general
      community setting. 3,939 participants of the Rotterdam Study aged 55 years and
      older for whom data from ophthalmic examinations at baseline and follow-up were
      available and who did not have glaucoma at baseline were included (baseline
      examination from 1991 to 1993; follow-up examinations from 1997 to 1999 and from
      2002 to 2006). Ophthalmic examinations, including measurement of the intraocular
      pressure, assessment of the optic nerve head and perimetry, were performed at
      baseline and follow-up. The use of corticosteroids was monitored continuously
      during follow-up. Corticosteroids were stratified into five groups: ophthalmic
      steroids, inhaled steroids, nasal steroids, oral steroids and steroid ointments.
      Associations between the use of corticosteroids and incident OAG were assessed
      using logistic regression models. The study outcome measures were the odds ratios
      (ORs) of associations between the use of corticosteroids and incident OAG.
      RESULTS: During a mean follow-up of 9.8 years, 108 participants (2.8%) developed
      OAG. The median number of steroid prescriptions during follow-up was 2 for
      ophthalmic, 7 for inhaled, 2 for nasal and 2 for oral steroids, and 3 for steroid
      ointments. The OR of the use of ophthalmic steroids was 1.04 [95% confidence
      interval (CI) 0.66, 1.65; p = 0.86], inhaled steroids 0.79 (95% CI 0.42, 1.48; p
      = 0.46), nasal steroids 1.26 (95% CI 0.74, 2.13; p = 0.40), oral steroids 1.03
      (95% CI 0.65, 1.64; p = 0.89) and steroid ointments 0.70 (95% CI 0.47, 1.05; p =
      0.086). These analyses were adjusted for age, sex, high myopia and family history
      of glaucoma. The small median numbers of prescriptions made it difficult to
      evaluate dose-response relationships. CONCLUSION: None of the classes of steroids
      were associated with the incidence of OAG in this elderly population.

PMID- 23150241
TI  - Synthesis of carbohydrates in a continuous flow reactor by immobilized
      phosphatase and aldolase.
AB  - Herein, we report a new flow process with immobilized enzymes to synthesize
      complex chiral carbohydrate analogues from achiral inexpensive building blocks in
      a three-step cascade reaction. The first reactor contained immobilized acid
      phosphatase, which phosphorylated dihydroxyacetone to dihydroxyacetone phosphate
      using pyrophosphate as the phosphate donor. The second flow reactor contained
      fructose-1,6-diphosphate aldolase (RAMA, rabbit muscle aldolase) or rhamnulose-1
      phosphate aldolase (RhuA from Thermotoga maritima) and acid phosphatase. The
      immobilized aldolases coupled the formed dihydroxyacetone phosphate to aldehydes,
      resulting in phosphorylated carbohydrates. A final reactor containing acid
      phosphatase that dephosphorylated the phosphorylated product yielded the final
      product. Different aldehydes were used to synthesize carbohydrates on a gram
      scale. To demonstrate the feasibility of the flow systems, we synthesized 0.6 g
      of the D-fagomine precursor. By using immobilized aldolase RhuA we were also able
      to obtain other stereoisomers of the D-fagomine precursor.

PMID- 23150243
TI  - Dihydrooxazine oxides as key intermediates in organocatalytic Michael additions
      of aldehydes to nitroalkenes.
AB  - Pause and play: dihydrooxazine oxides are stable intermediates that are
      protonated directly, without the intermediacy of the zwitterions, in
      organocatalytic Michael additions of aldehydes and nitroalkenes (see scheme,
      R=alkyl). Protonation of these species explains both the role of the acid co
      catalyst in these reactions, and the observed stereochemistry when the reaction
      is conducted with alpha-alkylnitroalkenes.

PMID- 23150242
TI  - Glycemic variability in hospitalized patients: choosing metrics while awaiting
      the evidence.
AB  - Hyperglycemia, hypoglycemia, preexisting diabetes, and glycemic variability each
      may affect hospital outcomes. Observational findings derived from randomized
      trials or retrospective studies suggest that independent of hypoglycemia and
      hyperglycemia, a relationship exists between variability and hospital outcomes. A
      review of studies conducted in diverse hospital populations is reported here,
      showing a relationship between measures of variability and nonglycemic outcomes,
      including ICU and hospital mortality and length of stay. "Glycemic variability"
      has an intuitive meaning, understood as a propensity of a single patient to
      develop repeated episodes of excursions of BG over a relatively short period of
      time that exceed the amplitude expected in normal physiology. It is proposed that
      each of 3 dimensions of variability should be separately studied: (1) magnitude
      of glycemic excursions during intervals of relative stability of the moving
      average of BG, (2) frequency with which a critical magnitude of excursion is
      exceeded, and (3) presence or absence of fine tuning. Multiple hospital studies
      have found that the standard deviation (SD) of the data set of blood glucose
      values (BG) of individual patients predicts outcomes. An appropriate refinement
      would be to report the "Reverse-transformed group mean of the SD of the
      logarithmically transformed BG data set of each patient," with confidence
      intervals. In logarithmic space, group means of the SD of BGs of each patient may
      be compared, using an appropriate parametric test. Upon reverse transformation,
      the upper and lower bounds of the confidence intervals become asymmetric about
      the reverse-transformed group mean of the SD. There is a need to understand what
      patterns of dispersion of BG over time are captured by SD as a predictor of
      outcomes. Among the causes of high SD, a subgroup may consist of patients having
      frequent oscillations of BG. Another subgroup may consist of patients
      experiencing a major change of overall glycemia during the timeframe of data
      collection. Appropriate metrics should be developed to recognize both variability
      in the sense of recurrent large oscillations of BG, and separately to recognize
      any time-dependent change of overall glycemia during hospitalization. Especially
      in relation to uncontrolled diabetes, there is a need to know whether rapid
      correction of chronic hyperglycemia adversely affects hospital outcomes. We have
      some understanding of how to control or prevent change of overall glycemia, and
      less understanding of how to control variability. Each may be associated with
      outcomes, and each may be detected by a high SD, but it remains uncertain whether
      intervention to prevent either pattern of changing glycemia would affect
      outcomes.

PMID- 23150244
TI  - Chromatin organization, epigenetics and differentiation: an evolutionary
      perspective.
AB  - Genome packaging is a universal phenomenon from prokaryotes to higher mammals.
      Genomic constituents and forces have however, travelled a long evolutionary
      route. Both DNA and protein elements constitute the genome and also aid in its
      dynamicity. With the evolution of organisms, these have experienced several
      structural and functional changes. These evolutionary changes were made to meet
      the challenging scenario of evolving organisms. This review discusses in detail
      the evolutionary perspective and functionality gain in the phenomena of genome
      organization and epigenetics.

PMID- 23150245
TI  - Secondary structures of the core histone N-terminal tails: their role in
      regulating chromatin structure.
AB  - The core histone N-terminal tails dissociate from their binding positions in
      nucleosomes at moderate salt concentrations, and appear unstructured in the
      crystal. This suggested that the tails contributed minimally to chromatin
      structure. However, in vitro studies have shown that the tails were involved in a
      range of intra- and inter-nucleosomal as well as inter-fibre contacts. The H4
      tail, which is essential for chromatin compaction, was shown to contact an
      adjacent nucleosome in the crystal. Acetylation of H4K16 was shown to abolish the
      ability of a nucleosome array to fold into a 30 nm fibre. The application of
      secondary structure prediction software has suggested the presence of extended
      structured regions in the histone tails. Molecular Dynamics studies have further
      shown that sections of the H3 and H4 tails assumed alpha-helical and beta-strand
      content that was enhanced by the presence of DNA, and that post-translational
      modifications of the tails had a major impact on these structures. Circular
      dichroism and NMR showed that the H3 and H4 tails exhibited significant alpha
      helical content, that was increased by acetylation of the tail. There is thus
      strong evidence, both from biophysical and from computational approaches, that
      the core histones tails, particularly that of H3 and H4, are structured, and that
      these structures are influenced by post-translational modifications. This chapter
      reviews studies on the position, binding sites and secondary structures of the
      core histone tails, and discusses the possible role of the histone tail
      structures in the regulation of chromatin organization, and its impact on human
      disease.

PMID- 23150246
TI  - Megabase replication domains along the human genome: relation to chromatin
      structure and genome organisation.
AB  - In higher eukaryotes, the absence of specific sequence motifs, marking the
      origins of replication has been a serious hindrance to the understanding of (i)
      the mechanisms that regulate the spatio-temporal replication program, and (ii)
      the links between origins activation, chromatin structure and transcription. In
      this chapter, we review the partitioning of the human genome into megabased-size
      replication domains delineated as N-shaped motifs in the strand compositional
      asymmetry profiles. They collectively span 28.3% of the genome and are bordered
      by more than 1,000 putative replication origins. We recapitulate the comparison
      of this partition of the human genome with high-resolution experimental data that
      confirms that replication domain borders are likely to be preferential
      replication initiation zones in the germline. In addition, we highlight the
      specific distribution of experimental and numerical chromatin marks along
      replication domains. Domain borders correspond to particular open chromatin
      regions, possibly encoded in the DNA sequence, and around which replication and
      transcription are highly coordinated. These regions also present a high
      evolutionary breakpoint density, suggesting that susceptibility to breakage might
      be linked to local open chromatin fiber state. Altogether, this chapter presents
      a compartmentalization of the human genome into replication domains that are
      landmarks of the human genome organization and are likely to play a key role in
      genome dynamics during evolution and in pathological situations.

PMID- 23150247
TI  - Role of DNA methyltransferases in epigenetic regulation in bacteria.
AB  - In prokaryotes, alteration in gene expression was observed with the modification
      of DNA, especially DNA methylation. Such changes are inherited from generation to
      generation with no alterations in the DNA sequence and represent the epigenetic
      signal in prokaryotes. DNA methyltransferases are enzymes involved in DNA
      modification and thus in epigenetic regulation of gene expression. DNA
      methylation not only affects the thermodynamic stability of DNA, but also changes
      its curvature. Methylation of specific residues on DNA can affect the protein-DNA
      interactions. DNA methylation in prokaryotes regulates a number of physiological
      processes in the bacterial cell including transcription, DNA mismatch repair and
      replication initiation. Significantly, many reports have suggested a role of DNA
      methylation in regulating the expression of a number of genes in virulence and
      pathogenesis thus, making DNA methlytransferases novel targets for the designing
      of therapeutics. Here, we summarize the current knowledge about the influence of
      DNA methylation on gene regulation in different bacteria, and on bacterial
      virulence.

PMID- 23150248
TI  - Metabolic aspects of epigenome: coupling of S-adenosylmethionine synthesis and
      gene regulation on chromatin by SAMIT module.
AB  - Histone and DNA methyltransferases utilize S-adenosyl-L-methionine (SAM), a key
      intermediate of sulfur amino acid metabolism, as a donor of methyl group. SAM is
      biosynthesized by methionine adenosyltransferase (MAT) using two substrates,
      methionine and ATP. Three distinct forms of MAT (MATI, MATII and MATIII), encoded
      by two distinct genes (MAT1A and MAT2A), have been identified in mammals. MATII
      consists of alpha2 catalytic subunit encoded by MAT2A and beta regulatory subunit
      encoded by MAT2B, but the physiological function of the beta subunit is not
      clear. MafK is a member of Maf oncoproteins and functions as both transcription
      activator and repressor by forming diverse heterodimers to bind to DNA elements
      termed Maf recognition elements. Proteomics analysis of MafK-interactome revealed
      its interaction with both MATIIalpha and MATIIbeta. They are recruited
      specifically to MafK target genes and are required for their repression by MafK
      and its partner Bach1. Because the catalytic activity of MATIIalpha is required
      for the MafK target gene repression, MATIIalpha is suggested to provide SAM
      locally on chromatin where it is recruited. One of the unexpected features of
      MATII is that MATIIalpha interacts with many chromatin-related proteins of
      diverse functions such as histone modification, chromatin remodeling,
      transcription regulation, and nucleo-cytoplasmic transport. MATIIalpha appears to
      generate multiple, heterogenous regulatory complexes where it provides SAM.
      Considering their function, the heterooligomer of MATIIalpha and beta is named
      SAMIT (SAM-integrating transcription) module within their interactome where it
      serves SAM for nuclear methyltransferases.

PMID- 23150249
TI  - Epigenetic regulation of male germ cell differentiation.
AB  - Male germ cell differentiation is a complex developmental program that produces
      highly specialized mature spermatozoa capable of independent movement and
      fertilization of an egg. Germ cells are unique in their capability to generate
      new organisms, and extra caution has to be taken to secure the correct
      inheritance of genetic and epigenetic information. Male germ cells are
      epigenetically distinct from somatic cells and they undergo several important
      epigenetic transitions. In primordial germ cells (PGCs), epigenome is
      reprogrammed by genome-wide resetting of epigenetic marks, including the sex
      specific imprinting of certain genes. Postnatal spermatogenesis is characterized
      by drastic chromatin rearrangements during meiotic recombination, sex chromosome
      silencing, and compaction of sperm nuclei, which is accomplished by replacing
      near to all histones by sperm-specific protamines. Small RNAs, including
      microRNAs (miRNAs), endogenous small interfering RNAs (endo-siRNAs) and PIWI
      interacting RNAs (piRNAs) are also involved in the control of male gamete
      production. The activities of small RNAs in male germ cells are diverse, and
      include miRNA- and endo-siRNA-mediated posttranscriptional mRNA regulation and
      piRNA-driven transposon silencing and the control of DNA methylation in PGCs. In
      this chapter, we give a brief review on the epigenetic processes that govern
      chromatin organization and germline-specific gene expression in differentiating
      male germ cells.

PMID- 23150250
TI  - Epigenetic regulation of skeletal muscle development and differentiation.
AB  - Skeletal muscle cells have served as a paradigm for understanding mechanisms
      leading to cellular differentiation. Formation of skeletal muscle involves a
      series of steps in which cells are committed towards the myogenic lineage,
      undergo expansion to give rise to myoblasts that differentiate into
      multinucleated myotubes, and mature to form adult muscle fibers. The commitment,
      proliferation, and differentiation of progenitor cells involve both genetic and
      epigenetic changes that culminate in alterations in gene expression. Members of
      the Myogenic regulatory factor (MRF), as well as the Myocyte Enhancer Factor
      (MEF2) families control distinct steps of skeletal muscle proliferation and
      differentiation. In addition, -growing evidence indicates that chromatin
      modifying enzymes and remodeling complexes epigenetically reprogram muscle
      promoters at various stages that preclude or promote MRF and MEF2 activites.
      Among these, histone deacetylases (HDACs), histone acetyltransferases (HATs),
      histone methyltransferases (HMTs) and SWI/SNF complexes alter chromatin structure
      through post-translational modifications to impact MRF and MEF2 activities. With
      such new and emerging knowledge, we are beginning to develop a true molecular
      understanding of the mechanisms by which skeletal muscle development and
      differentiation is regulated. Elucidation of the mechanisms by which epigenetic
      regulators control myogenesis will likely provide a new foundation for the
      development of novel therapeutic drugs for muscle dystrophies, ageing-related
      regeneration defects that occur due to altered proliferation and differentiation,
      and other malignancies.

PMID- 23150251
TI  - Small changes, big effects: chromatin goes aging.
AB  - Aging is a complex trait and is influenced by multiple factors that are both
      intrinsic and extrinsic to the organism (Kirkwood et al. 2000; Knight 2000).
      Efforts to understanding the mechanisms that extend or shorten lifespan have been
      made since the early twentieth century. Aging is characteristically associated
      with a progressive decline in the overall fitness of the organism. Several
      studies have provided valuable information about the molecular events that
      accompany this process and include accumulation of nuclear and mitochondrial
      mutations, shortened and dysfunctional telomeres, oxidative damage of
      protein/DNA, senescence and apoptosis (Muller 2009). Clinical studies and work on
      model organisms have shown that there is an increased susceptibility to
      conditions such as neurological disorders, diabetes, cardiovascular diseases,
      degenerative syndromes and even cancers, with age (Arvanitakis et al. 2006; Lee
      and Kim 2006; Rodriguez and Fraga 2010).

PMID- 23150252
TI  - Homeotic gene regulation: a paradigm for epigenetic mechanisms underlying
      organismal development.
AB  - The organization of eukaryotic genome into chromatin within the nucleus
      eventually dictates the cell type specific expression pattern of genes. This
      higher order of chromatin organization is established during development and
      dynamically maintained throughout the life span. Developmental mechanisms are
      conserved in bilaterians and hence they have body plan in common, which is
      achieved by regulatory networks controlling cell type specific gene expression.
      Homeotic genes are conserved in metazoans and are crucial for animal development
      as they specify cell type identity along the anterior-posterior body axis. Hox
      genes are the best studied in the context of epigenetic regulation that has led
      to significant understanding of the organismal development. Epigenome specific
      regulation is brought about by conserved chromatin modulating factors like
      PcG/trxG proteins during development and differentiation. Here we discuss the
      conserved epigenetic mechanisms relevant to homeotic gene regulation in
      metazoans.

PMID- 23150254
TI  - The RNA polymerase II transcriptional machinery and its epigenetic context.
AB  - RNA polymerase II (Pol II) is the main engine that drives transcription of
      protein-encoding genes in eukaryotes. Despite its intrinsic subunit complexity,
      Pol II is subject to a host of factors that regulate the multistep transcription
      process. Indeed, the hallmark of the transcription cycle is the dynamic
      association of Pol II with initiation, elongation and other factors. In addition,
      Pol II transcription is regulated by a series of cofactors (coactivators and
      corepressors). Among these, the Mediator has emerged as one of the key regulatory
      factors for Pol II. Transcription by Pol II takes place in the context of
      chromatin, which is subject to numerous epigenetic modifications. This chapter
      mainly summarizes the various biochemical mechanisms that determine formation and
      function of a Pol II preinitiation complex (PIC) and those that affect its
      progress along the gene body (elongation). It further examines the various
      epigenetic modifications that the Pol II machinery encounters, especially in
      certain developmental contexts, and highlights newer evidence pointing to a
      likely close interplay between this machinery and factors responsible for the
      chromatin modifications.

PMID- 23150255
TI  - RNA polymerase III transcription - regulated by chromatin structure and regulator
      of nuclear chromatin organization.
AB  - RNA polymerase III (Pol III) transcription is regulated by modifications of the
      chromatin. DNA methylation and post-translational modifications of histones, such
      as acetylation, phosphorylation and methylation have been linked to Pol III
      transcriptional activity. In addition to being regulated by modifications of DNA
      and histones, Pol III genes and its transcription factors have been implicated in
      the organization of nuclear chromatin in several organisms. In yeast, the ability
      of the Pol III transcription system to contribute to nuclear organization seems
      to be dependent on direct interactions of Pol III genes and/or its transcription
      factors TFIIIC and TFIIIB with the structural maintenance of chromatin (SMC)
      protein-containing complexes cohesin and condensin. In human cells, Pol III genes
      and transcription factors have also been shown to colocalize with cohesin and the
      transcription regulator and genome organizer CCCTC-binding factor (CTCF).
      Furthermore, chromosomal sites have been identified in yeast and humans that are
      bound by partial Pol III machineries (extra TFIIIC sites - ETC; chromosome
      organizing clamps - COC). These ETCs/COC as well as Pol III genes possess the
      ability to act as boundary elements that restrict spreading of heterochromatin.

PMID- 23150256
TI  - The role of DNA methylation and histone modifications in transcriptional
      regulation in humans.
AB  - Although the field of genetics has grown by leaps and bounds within the last
      decade due to the completion and availability of the human genome sequence,
      transcriptional regulation still cannot be explained solely by an individual's
      DNA sequence. Complex coordination and communication between a plethora of well
      conserved chromatin modifying factors are essential for all organisms. Regulation
      of gene expression depends on histone post translational modifications (HPTMs),
      DNA methylation, histone variants, remodeling enzymes, and effector proteins that
      influence the structure and function of chromatin, which affects a broad spectrum
      of cellular processes such as DNA repair, DNA replication, growth, and
      proliferation. If mutated or deleted, many of these factors can result in human
      disease at the level of transcriptional regulation. The common goal of recent
      studies is to understand disease states at the stage of altered gene expression.
      Utilizing information gained from new high-throughput techniques and analyses
      will aid biomedical research in the development of treatments that work at one of
      the most basic levels of gene expression, chromatin. This chapter will discuss
      the effects of and mechanism by which histone modifications and DNA methylation
      affect transcriptional regulation.

PMID- 23150257
TI  - Histone variants and transcription regulation.
AB  - Histones are the protein components of chromatin and are important for its
      organization and compaction. Although core histones are exclusively expressed
      during S phase of the cell cycle, there exist variants of canonical histones that
      are expressed throughout the cell cycle. These histone variants are often
      deposited at defined regions of the genome and they play important roles in a
      variety of cellular processes, such as transcription regulation, heterochromatin
      formation and DNA repair. In this chapter, we will focus on several histone
      variants that have been linked to transcription regulation, and highlight their
      physical and functional features that facilitate their activities in this
      context.

PMID- 23150253
TI  - Basic mechanisms in RNA polymerase I transcription of the ribosomal RNA genes.
AB  - RNA Polymerase (Pol) I produces ribosomal (r)RNA, an essential component of the
      cellular protein synthetic machinery that drives cell growth, underlying many
      fundamental cellular processes. Extensive research into the mechanisms governing
      transcription by Pol I has revealed an intricate set of control mechanisms
      impinging upon rRNA production. Pol I-specific transcription factors guide Pol I
      to the rDNA promoter and contribute to multiple rounds of transcription
      initiation, promoter escape, elongation and termination. In addition, many
      accessory factors are now known to assist at each stage of this transcription
      cycle, some of which allow the integration of transcriptional activity with
      metabolic demands. The organisation and accessibility of rDNA chromatin also
      impinge upon Pol I output, and complex mechanisms ensure the appropriate
      maintenance of the epigenetic state of the nucleolar genome and its effective
      transcription by Pol I. The following review presents our current understanding
      of the components of the Pol I transcription machinery, their functions and
      regulation by associated factors, and the mechanisms operating to ensure the
      proper transcription of rDNA chromatin. The importance of such stringent control
      is demonstrated by the fact that deregulated Pol I transcription is a feature of
      cancer and other disorders characterised by abnormal translational capacity.

PMID- 23150258
TI  - Noncoding RNAs in chromatin organization and transcription regulation: an
      epigenetic view.
AB  - The Genome of a eukaryotic cell harbors genetic material in the form of DNA which
      carries the hereditary information encoded in their bases. Nucleotide bases of
      DNA are transcribed into complimentary RNA bases which are further translated
      into protein, performing defined set of functions. The central dogma of life
      ensures sequential flow of genetic information among these biopolymers. Noncoding
      RNAs (ncRNAs) serve as exceptions for this principle as they do not code for any
      protein. Nevertheless, a major portion of the human transcriptome comprises
      noncoding RNAs. These RNAs vary in size, as well as they vary in the spatio
      temporal distribution. These ncRnAs are functional and are shown to be involved
      in diverse cellular activities. Precise location and expression of ncRNA is
      essential for the cellular homeostasis. Failures of these events ultimately
      results in numerous disease conditions including cancer. The present review lists
      out the various classes of ncRNAs with a special emphasis on their role in
      chromatin organization and transcription regulation.

PMID- 23150259
TI  - Chromatin structure and organization: the relation with gene expression during
      development and disease.
AB  - The elementary level of chromatin fiber, namely the nucleofilament, is known to
      undergo a hierarchical compaction leading to local chromatin loops, then
      chromatin domains and ultimately chromosome territories. These successive folding
      levels rely on the formation of chromatin loops ranging from few kb to some Mb.
      In addition to a packaging and structural role, the high-order organization of
      genomes functionally impacts on gene expression program. This review summarises
      to which extent each level of chromatin compaction does affect gene regulation.
      In addition, we point out the structural and functional changes observed in
      diseases. Emphasis will be mainly placed on the large-scale organization of the
      chromatin.

PMID- 23150260
TI  - Cancer: an epigenetic landscape.

PMID- 23150261
TI  - Epigenetic regulation of cancer stem cell gene expression.
AB  - The concept of cancer as a stem cell disease has slowly gained ground over the
      last decade. A 'stem-like' state essentially necessitates that some cells in the
      developing tumor express the properties of remaining quiescent, self-renewing and
      regenerating tumors through establishment of aberrant cellular hierarchies.
      Alternatively, such capacities may also be reacquired through a de
      differentiation process. The abnormal cellular differentiation patterns involved
      during either process during carcinogenesis are likely to be driven through a
      combination of genetic events and epigenetic regulation. The role(s) of the
      latter is increasingly being appreciated in acquiring the requisite genomic
      specificity and flexibility required for phenotypic plasticity, specifically in a
      context wherein genome sequences are not altered for differentiation to ensue. In
      this chapter, the recent advances in elucidating epigenetic mechanisms that
      govern the self-renewal, differentiation and regenerative potentials of cancer
      stem cells will be presented.

PMID- 23150262
TI  - Role of epigenetic mechanisms in the vascular complications of diabetes.
AB  - Diabetes and metabolic disorders are leading causes of micro- and macrovascular
      complications. Furthermore, efforts to treat these complications are hampered by
      metabolic memory, a phenomenon in which prior exposure to hyperglycemia
      predisposes diabetic patients to the continued development of vascular diseases
      despite subsequent glycemic control. Persistently increased levels of oxidant
      stress and inflammatory genes are key features of these pathologies. Biochemical
      and molecular studies showed that hyperglycemia induced activation of NF-kappaB,
      signaling and actions of advanced glycation end products and other inflammatory
      mediators play key roles in the expression of pathological genes. In addition,
      epigenetic mechanisms such as posttranslational modification of histones and DNA
      methylation also play central roles in gene regulation by affecting chromatin
      structure and function. Recent studies have suggested that dysregulation of such
      epigenetic mechanisms may be involved in metabolic memory leading to persistent
      changes in the expression of genes associated with diabetic vascular
      complications. Further exploration of these mechanisms by also taking advantages
      of recent advances in high throughput epigenomics technologies will greatly
      increase our understanding of epigenetic variations in diabetes and its
      complications. This in turn can lead to the development of novel new therapies.

PMID- 23150263
TI  - Epigenetic changes in inflammatory and autoimmune diseases.
AB  - In higher eukaryotic organisms epigenetic modifications are crucial for proper
      chromatin folding and thereby proper regulation of gene expression. In the last
      years the involvement of aberrant epigenetic modifications in inflammatory and
      autoimmune diseases has been recognized and attracted significant interest.
      However, the epigenetic mechanisms underlying the different disease phenotypes
      are still poorly understood. As autoimmune and inflammatory diseases are at least
      partly T cell mediated, we will provide in this chapter an introduction to the
      epigenetics of T cell differentiation followed by a summary of the current
      knowledge on aberrant epigenetic modifications that dysfunctional T cells display
      in various diseases such as type 1 diabetes, rheumatoid arthritis, systemic lupus
      erythematosus, multiple sclerosis, inflammatory bowel disease, and asthma.

PMID- 23150264
TI  - Epigenetic regulation of HIV-1 persistence and evolving strategies for virus
      eradication.
AB  - Despite the intense effort put by researchers globally to understand Human
      Immunodeficiency Virus (HIV-1) pathogenesis since its discovery 30 years ago, the
      acquired knowledge till date is not good enough to eradicate HIV-1 from an
      infected individual. HIV-1 infects cells of the human immune system and
      integrates into the host cell genome thereby leading to persistent infection in
      these cells. Based on the activation status of the cells, the infection could be
      productive or result in latent infection. The current regimen used to treat HIV-1
      infection in an AIDS patient includes combination of antiretroviral drugs called
      Highly Active Anti-Retroviral Therapy (HAART). A major challenge for the success
      of HAART has been these latent reservoirs of HIV which remain hidden and pose
      major hurdle for the eradication of virus. Combination of HAART therapy with
      simultaneous activation of latent reservoirs of HIV-1 seems to be the future of
      anti-retroviral therapy; however, this will require a much better understanding
      of the mechanisms and regulation of HIV-1 latency. In this chapter, we have tried
      to elaborate on HIV-1 latency, highlighting the strategies employed by the virus
      to ensure persistence in the host with specific focus on epigenetic regulation of
      latency. A complete understanding of HIV-1 latency will be extremely essential
      for ultimate eradication of HIV-1 from the human host.

PMID- 23150265
TI  - Epigenetics in Parkinson's and Alzheimer's diseases.
AB  - Neurodegenerative disorders, such as Parkinson's and Alzheimer's disease, are
      highly complex, due to their multifactorial origin, not only depending on genetic
      but also on environmental factors. Several genetic risk factors have already been
      associated with both the diseases, however, the precise way through which the
      environment contributes to neurodegeneration is still unclear.Recently,
      epigenetic mechanisms, such as DNA methylation, chromatin remodeling or miRNAs,
      which may induce alterations in genes expression, have started to be implicated
      in both AD and PD. Epigenetic modulation is present since pre-natal stages and
      throughout lifetime, and depends on lifestyle conditions and environmental
      exposures, and consequently could represent the missing link between risk factors
      and the development of sporadic disorders. This chapter will discusses the role
      of epigenetics in AD and PD.

PMID- 23150266
TI  - Cellular redox, epigenetics and diseases.
AB  - Since the Central dogma of Molecular Biology was proposed about 40 years ago; our
      understanding of the intricacies of gene regulation has undergone tectonic shifts
      almost every decade. It is now widely accepted that the complexity of an organism
      is not directed by the sheer number of genes it carries but how they are decoded
      by a myriad of regulatory modules. Over the years, it has emerged that the
      organizations chromatins and its remodeling; splicing and polyadenylation of pre
      mRNAs, stability and localization of mRNAs and modulation of their expression by
      non-coding and miRNAs play pivotal roles in metazoan gene expression.
      Nevertheless, in spite of tremendous progress in our understanding of all these
      mechanisms of gene regulation, the way these events are coordinated leading
      towards a highly defined proteome of a given cell type remains enigmatic. In that
      context, the structures of many metazoan genes cannot fully explain their pattern
      of expression in different tissues, especially during embryonic development and
      progression of various diseases. Further, numerous studies done during the past
      quarter of a century suggested that the heritable states of transcriptional
      activation or repression of a gene can be influenced by the covalent
      modifications of constituent bases and associated histones; its chromosomal
      context and long-range interactions between various chromosomal elements
      (Holliday 1987; Turner 1998; Lyon 1993). However, molecular dissection of these
      phenomena is largely unknown and is an exciting topic of research under the sub
      discipline epigenetics (Gasser et al. 1998).

PMID- 23150267
TI  - Stem cell plasticity in development and cancer: epigenetic origin of cancer stem
      cells.
AB  - Stem cells are unique cells that can self-renew and differentiate into many cell
      types. Plasticity is a fundamental characteristic of stem cells and it is
      regulated by reversible epigenetic modifications. Although gene-restriction
      programs are established during embryonic development when cell lineages are
      formed, stem cells retain a degree of flexibility that is essential for tissue
      regeneration. For instance, quiescent adult stem cells can be induced to
      proliferate and trans-differentiate in response to injury. The same degree of
      plasticity is observed in cancer, where cancer cells with stem cell
      characteristics (or cancer stem cells) are formed by transformation of normal
      stem cells or de-differentiation of somatic cells. Reprogramming experiments with
      normal somatic cells and cancer cells show that epigenetic landscapes are more
      plastic than originally thought and that their manipulation can induce changes in
      cell fate. Our knowledge of stem cell function is still limited and only by
      understanding the mechanisms regulating developmental potential together with the
      definition of epigenetic maps of normal and diseased tissues we can reveal the
      true extent of their plasticity. In return, the control of plastic epigenetic
      programs in stem cells will allow us to develop effective treatments for
      degenerative diseases and cancer.

PMID- 23150268
TI  - Histone acetylation as a therapeutic target.
AB  - The recent developments in the field of epigenetics have changed the way the
      covalent modifications were perceived from mere chemical tags to important
      biological recruiting platforms as well as decisive factors in the process of
      transcriptional regulation and gene expression. Over the years, the parallel
      investigations in the area of epigenetics and disease have also shown the
      significance of the epigenetic modifications as important regulatory nodes that
      exhibit dysfunction in disease states. In the present scenario where epigenetic
      therapy is also being considered at par with the conventional therapeutic
      strategies, this article reviews the role of histone acetylation as an epigenetic
      mark involved in different biological processes associated with normal as well as
      abnormal gene expression states, modulation of this acetylation by small
      molecules and warrants the possibility of acetylation as a therapeutic target.

PMID- 23150269
TI  - DNA methylation and cancer.
AB  - Cancer has been considered a genetic disease with a wide array of well
      characterized gene mutations and chromosomal abnormalities. Of late, aberrant
      epigenetic modifications have been elucidated in cancer, and together with
      genetic alterations, they have been helpful in understanding the complex traits
      observed in neoplasia. "Cancer Epigenetics" therefore has contributed
      substantially towards understanding the complexity and diversity of various
      cancers. However, the positioning of epigenetic events during cancer progression
      is still not clear, though there are some reports implicating aberrant epigenetic
      modifications in very early stages of cancer. Amongst the most studied aberrant
      epigenetic modifications are the DNA methylation differences at the promoter
      regions of genes affecting their expression. Hypomethylation mediated increased
      expression of oncogenes and hypermethylation mediated silencing of tumor
      suppressor genes are well known examples. This chapter also explores the
      correlation of DNA methylation and demethylation enzymes with cancer.

PMID- 23150270
TI  - Role of epigenetics in inflammation-associated diseases.
AB  - There is considerable evidence suggesting that epigenetic mechanisms may mediate
      development of chronic inflammation by modulating the expression of pro
      inflammatory cytokine TNF-alpha, interleukins, tumor suppressor genes, oncogenes
      and autocrine and paracrine activation of the transcription factor NF-kappaB.
      These molecules are constitutively produced by a variety of cells under chronic
      inflammatory conditions, which in turn leads to the development of major diseases
      such as autoimmune disorders, chronic obstructive pulmonary diseases,
      neurodegenerative diseases and cancer. Distinct or global changes in the
      epigenetic landscape are hallmarks of chronic inflammation driven diseases.
      Epigenetics include changes to distinct markers on the genome and associated
      cellular transcriptional machinery that are copied during cell division (mitosis
      and meiosis). These changes appear for a short span of time and they necessarily
      do not make permanent changes to the primary DNA sequence itself. However, the
      most frequently observed epigenetic changes include aberrant DNA methylation, and
      histone acetylation and deacetylation. In this chapter, we focus on pro
      inflammatory molecules that are regulated by enzymes involved in epigenetic
      modifications such as arginine and lysine methyl transferases, DNA
      methyltransferase, histone acetyltransferases and histone deacetylases and their
      role in inflammation driven diseases. Agents that modulate or inhibit these
      epigenetic modifications, such as HAT or HDAC inhibitors have shown great
      potential in inhibiting the progression of these diseases. Given the plasticity
      of these epigenetic changes and their readiness to respond to intervention by
      small molecule inhibitors, there is a tremendous potential for the development of
      novel therapeutics that will serve as direct or adjuvant therapeutic compounds in
      the treatment of these diseases.

PMID- 23150271
TI  - Plasmodium falciparum: epigenetic control of var gene regulation and disease.
AB  - Plasmodium falciparum, one of the deadliest parasites on earth causes human
      malaria resulting one million deaths annually. Central to the parasite
      pathogenicity and morbidity is the switching of parasite virulence (var) gene
      expression causing host immune evasion. The regulation of Plasmodium var gene
      expression is poorly understood. The complex life cycle of Plasmodium and
      mutually exclusive expression pattern of var genes make this disease difficult to
      control. Recent studies have demonstrated the pivotal role of epigenetic
      mechanism for control of coordinated expression of var genes, important for
      various clinical manifestations of malaria. In this review, we discuss about
      different Plasmodium histones and their various modifications important for gene
      expression and gene repression.Contribution of epigenetic mechanism to understand
      the var gene expression is also highlighted. We also describe in details P.
      falciparum nuclear architecture including heterochromatin, euchromatin and
      telomeric regions and their importance in subtelomeric and centrally located var
      gene expression. Finally, we explore the possibility of using Histone Acetyl
      Transferase (HAT) and Histone Deacetylase (HDAC)inhibitors against multi-drug
      resistance malaria parasites to provide another line of treatment for malaria.

PMID- 23150272
TI  - Gold catalysis: catalyst oxidation state dependent dichotomy in the cyclization
      of furan-yne systems with aromatic tethers.
AB  - Four different synthetic strategies led to a variety of furan-yne systems that
      contained an aryl system in the tether. Due to the short routes to these systems
      (four steps or less), a small library of substrates could easily be prepared.
      These were treated with AuCl(3) or with the Gagosz's catalyst Ph(3)PAuNTf(2)
      complex. The AuCl(3)-catalyzed reactions delivered highly substituted fluorene
      derivatives, a class of compounds of great importance as precursors for
      luminophores with extraordinary abilities. Conversely, a different mechanistic
      pathway was observed with the cationic gold(I) catalyst. In the latter case, a
      mechanistically interesting reaction cascade initiated a formal alkyne insertion
      into the furyl-sp(3)-C bond, which gave indene derivatives as the final products.
      This new reaction pathway depends on the aromatic moiety in the tether, which
      stabilizes a crucial cationic intermediate as a benzylic cation.

PMID- 23150274
TI  - The financial costs of sadness.
AB  - We hypothesized a phenomenon that we term myopic misery. According to our
      hypothesis, sadness increases impatience and creates a myopic focus on obtaining
      money immediately instead of later. This focus, in turn, increases intertemporal
      discount rates and thereby produces substantial financial costs. In three
      experiments, we randomly assigned participants to sad- and neutral-state
      conditions, and then offered intertemporal choices. Disgust served as a
      comparison condition in Experiments 1 and 2. Sadness significantly increased
      impatience: Relative to median neutral-state participants, median sad-state
      participants accepted 13% to 34% less money immediately to avoid waiting 3 months
      for payment. In Experiment 2, impatient thoughts mediated the effects. Experiment
      3 revealed that sadness made people more present biased (i.e., wanting something
      immediately), but not globally more impatient. Disgusted participants were not
      more impatient than neutral participants, and that lack of difference implies
      that the same financial effects do not arise from all negative emotions. These
      results show that myopic misery is a robust and potentially harmful phenomenon.

PMID- 23150273
TI  - The adaptor protein LAT serves as an integration node for signaling pathways that
      drive T cell activation.
AB  - T cells are essential for the adaptive immune response to pathogens. However,
      dysfunctional T cell activity has been implicated in numerous diseases, including
      the failure of organ transplants, allergic reactions, asthma, autoimmune
      disorders, and coronary artery disease. T cell responses to pathogens require the
      induction of the primary activating receptor, the T cell receptor (TCR), along
      with other costimulatory and adhesion receptors. Signal transduction pathways
      activated downstream of these receptors drive T cell responses required for the
      immune response and disease progression. A key question in our understanding of
      the mechanism of T cell activation is how signaling pathways emanating from
      multiple receptors integrate together to alter T cell effector functions. One
      integration node for intracellular signaling is the membrane-associated adaptor
      protein linker for the activation of T cells or LAT. Upon stimulation of the TCR
      and other receptors, LAT is phosphorylated at several tyrosines residues on its
      cytoplasmic tail. This leads to the binding of SH2 domain-containing proteins and
      their associated molecules and the formation of large multiprotein complexes.
      These dynamic and highly regulated signaling complexes facilitate the production
      of second messengers, activate downstream pathways, induce actin cytoskeleton
      polymerization, and stimulate the activity of multiple transcription factors.
      Thus, signaling pathways from several receptors feed into LAT, which then
      integrates this information and selectively induces pathways critical for T cell
      activation and the adaptive immune response.

PMID- 23150275
TI  - The road to language learning is iconic: evidence from British Sign Language.
AB  - An arbitrary link between linguistic form and meaning is generally considered a
      universal feature of language. However, iconic (i.e., nonarbitrary) mappings
      between properties of meaning and features of linguistic form are also widely
      present across languages, especially signed languages. Although recent research
      has shown a role for sign iconicity in language processing, research on the role
      of iconicity in sign-language development has been mixed. In this article, we
      present clear evidence that iconicity plays a role in sign-language acquisition
      for both the comprehension and production of signs. Signed languages were taken
      as a starting point because they tend to encode a higher degree of iconic form
      meaning mappings in their lexicons than spoken languages do, but our findings are
      more broadly applicable: Specifically, we hypothesize that iconicity is
      fundamental to all languages (signed and spoken) and that it serves to bridge the
      gap between linguistic form and human experience.

PMID- 23150276
TI  - Unlocking past emotion: verb use affects mood and happiness.
AB  - In the research reported here, I examined whether the verbs applied to
      descriptions of past emotional experiences influence present mood and happiness.
      Participants who described a positive experience using the imperfective aspect,
      which implies ongoing progression, subsequently reported more positive mood and
      greater happiness than did participants who described a positive experience using
      the perfective aspect, which implies completion; likewise, participants who
      described a negative experience using the imperfective aspect subsequently
      reported more negative mood and less happiness than did participants who
      described a negative experience using the perfective aspect. These effects were
      traced to enhanced memory for the described emotional experience in the
      imperfective condition relative to the perfective condition. The findings
      demonstrate how formal features of language shape both the reinstatement of past
      affective reactions and happiness judgments, and may have practical applications
      for improving subjective well-being.

PMID- 23150277
TI  - Tall, dark, and stable: embodiment motivates mate selection preferences.

PMID- 23150279
TI  - Association between urinary markers of nucleic acid oxidation and mortality in
      type 2 diabetes: a population-based cohort study.
AB  - OBJECTIVE: We recently showed that RNA oxidation, estimated by urinary excretion
      of 8-oxo-7,8-dihydroguanosine (8-oxoGuo), independently predicted mortality in a
      cohort of 1,381 treatment-naive patients with newly diagnosed type 2 diabetes. In
      the present investigation, we analyzed urine collected 6 years after the
      diagnosis to assess the association between urinary markers of nucleic acid
      oxidation and mortality in patients with established and treated diabetes.
      RESEARCH DESIGN AND METHODS: We used data from the 970 patients who attended the
      screening for diabetes complications 6 years after the diagnosis. Cox
      proportional hazards regression was used to examine the relationship between
      urinary markers of DNA oxidation (8-oxo-7,8-dihydro-2'-deoxyguanosine [8-oxodG]
      [n = 938]) and RNA oxidation (8-oxoGuo [n = 936]) and mortality. RESULTS: During
      a median of 9.8 years of follow-up, 654 patients died. Urinary 8-oxoGuo assessed
      6 years after the diagnosis was significantly associated with mortality. The
      multivariate-adjusted hazard ratios for all-cause and diabetes-related mortality
      of patients with 8-oxoGuo levels in the highest quartile compared with those in
      the lowest quartile were 1.86 (95% CI 1.34-2.58) and 1.72 (1.11-2.66),
      respectively. Conversely, 8-oxodG was not associated with mortality. In addition,
      we found an association between changes in 8-oxoGuo from diagnosis to 6-year
      follow-up and mortality, with increased risk in patients with an increase and
      decreased risk in patients with a decrease in 8-oxoGuo. CONCLUSIONS: The RNA
      oxidation marker 8-oxoGuo is an independent predictor of mortality in patients
      with established and treated type 2 diabetes, and changes in 8-oxoGuo during the
      first 6 years after diagnosis are associated with mortality.

PMID- 23150278
TI  - Tandem mass spectrometry for characterization of covalent adducts of DNA with
      anticancer therapeutics.
AB  - The chemotherapeutic activities of many anticancer and antibacterial drugs arise
      from their interactions with nucleic acid substrates. Some of these ligands
      interact with DNA in a way that causes conformational changes or damage to the
      nucleic acid targets, ultimately altering recognition by key DNA-specific
      enzymes, interfering with DNA transcription or prohibiting replication, and
      terminating cell growth and proliferation. The design and synthesis of ligands
      that bind to nucleic acids remains a dynamic field in medicinal chemistry and
      pharmaceutical research. The quest for more selective and efficacious DNA
      interactive anticancer chemotherapeutics has likewise catalyzed the need for
      sensitive analytical methods that can provide structural information about the
      nature of the resulting DNA adducts and provide insight into the mechanistic
      pathways of the DNA/drug interactions and the impact on the cellular processes in
      biological systems. This review focuses on the array of tandem mass spectrometric
      strategies developed and applied for characterization of covalent adducts formed
      between DNA and anticancer ligands.

PMID- 23150280
TI  - Transient neonatal diabetes, ZFP57, and hypomethylation of multiple imprinted
      loci: a detailed follow-up.
AB  - OBJECTIVE: Transient neonatal diabetes mellitus 1 (TNDM1) is the most common
      cause of diabetes presenting at birth. Approximately 5% of the cases are due to
      recessive ZFP57 mutations, causing hypomethylation at the TNDM locus and other
      imprinted loci (HIL). This has consequences for patient care because it has
      impact on the phenotype and recurrence risk for families. We have determined the
      genotype, phenotype, and epigenotype of the first 10 families to alert health
      professionals to this newly described genetic subgroup of diabetes. RESEARCH
      DESIGN AND METHODS: The 10 families (14 homozygous/compound heterozygous
      individuals) with ZFP57 mutations were ascertained through TNDM1 diagnostic
      testing. ZFP57 was sequenced in probands and their relatives, and the methylation
      levels at multiple maternally and paternally imprinted loci were determined.
      Medical and family histories were obtained, and clinical examination was
      performed. RESULTS: The key clinical features in probands were transient neonatal
      diabetes, intrauterine growth retardation, macroglossia, heart defects, and
      developmental delay. However, the finding of two homozygous relatives without
      diabetes and normal intelligence showed that the phenotype could be very
      variable. The epigenotype always included total loss of methylation at the TNDM1
      locus and reproducible combinations of differential hypomethylation at other
      maternally imprinted loci, including tissue mosaicism. CONCLUSIONS: There is yet
      no clear genotype-epigenotype-phenotype correlation to explain the variable
      clinical presentation, and this results in difficulties predicting the prognosis
      of affected individuals. However, many cases have a more severe phenotype than
      seen in other causes of TNDM1. Further cases and global epigenetic testing are
      needed to clarify this.

PMID- 23150281
TI  - Population-based cohort analyses of the bidirectional relationship between type 2
      diabetes and depression.
AB  - OBJECTIVE: This study addresses the strength of association for the bidirectional
      relationship between type 2 diabetes and depression. RESEARCH DESIGN AND METHODS:
      We used two cohort studies with the same source of database to determine the link
      between depression and type 2 diabetes. The data analyzed included a random
      sample of 1 million beneficiaries selected from the National Health Insurance
      claims in 2000. The analysis of diabetes predicting the depression onset
      consisted of 16,957 diabetic patients and the same number of sex- and age-matched
      nondiabetic control subjects. The analysis of depression predicting diabetes
      onset included 5,847 depressive patients and 5,847 sex- and age-matched
      nondepressive control subjects. The follow-up period was between 2000 and 2006,
      and onset of end points was identified from ambulatory care claims. The Cox
      proportional hazards regression model adjusted for potential confounders was used
      to estimate relative hazards. RESULTS: The first cohort analysis noted an
      incidence density (ID) of 7.03 per 1,000 person-years (PY) and 5.04 per 1,000 PY
      for depression in diabetic and nondiabetic subjects, respectively, representing a
      covariate-adjusted hazard ratio (HR) of 1.43 (95% CI 1.16-1.77). The second
      cohort analysis noted an ID of 27.59 per 1,000 PY and 9.22 per 1,000 PY for
      diabetes in depressive and nondepressive subjects, respectively. The covariate
      adjusted HR was stronger at 2.02 (1.80-2.27) for incident diabetes associated
      with baseline depression. CONCLUSIONS: The two cohort studies provided evidence
      for the bidirectional relationship between diabetes and depression, with a
      stronger association noted for the depression predicting onset of diabetes.

PMID- 23150282
TI  - Decreased reactivity of skin microcirculation in response to L-arginine in later
      onset type 1 diabetes.
AB  - OBJECTIVE: The aim of our study was to evaluate the vasodilatory effect of l
      arginine infusion on the skin microcirculation and to assess the relationship
      between this effect and the presence of microangiopathy in patients with type 1
      diabetes. RESEARCH DESIGN AND METHODS: Capillaroscopy was performed before and
      after l-arginine infusion in 48 diabetic patients (26 women and 22 men; age, 39.8
      +/- 6.3 years) and 24 volunteers free of any chronic disease (13 women and 11
      men; age, 38.0 +/- 6.7 years). The skin microcirculation reactivity, as expressed
      by the percentage of area covered by capillaries (coverage) and the distance
      between capillaries (distance), and the relationship between microcirculation
      reactivity and the presence of microangiopathic complications were assessed.
      RESULTS: The distance before l-arginine infusion was significantly lower in
      patients than in controls (221 [153-311] vs. 240 [185-356] um; P = 0.02) and did
      not differ after l-arginine infusion (223.5 [127-318] vs. 242.5 [181-341] um; P =
      0.27). The difference between the coverage values obtained before and after l
      arginine infusion (Deltacoverage) was significantly different from zero in the
      control group but not in the diabetes group. Patients with later onset of
      diabetes were characterized by decreased skin microcirculation reactivity when
      compared with patients with earlier onset of diabetes (-1.18 [-5.07 to 11.60] vs.
      1.36 [-6.00 to 8.06]; P = 0.02) despite the higher prevalence of retinopathy in
      patients with earlier onset of diabetes (64% vs. 26%; P = 0.02). CONCLUSIONS:
      Skin microvascular reactivity is impaired in patients with later onset of type 1
      diabetes. Capillaroscopy with l-arginine infusion is useful for the
      identification of skin microangiopathy in type 1 diabetes.

PMID- 23150283
TI  - Heterogeneity in phenotype of usher-congenital hyperinsulinism syndrome: hearing
      loss, retinitis pigmentosa, and hyperinsulinemic hypoglycemia ranging from severe
      to mild with conversion to diabetes.
AB  - OBJECTIVE: To evaluate the phenotype of 15 children with congenital
      hyperinsulinism (CHI) and profound hearing loss, known as Homozygous 11p15-p14
      Deletion syndrome (MIM #606528). RESEARCH DESIGN AND METHODS: Prospective
      clinical follow-up and genetic analysis by direct sequencing, multiplex ligation
      dependent probe amplification, and microsatellite markers. RESULTS: Genetic
      testing identified the previous described homozygous deletion in 11p15,
      USH1C:c.(90+592)_ABCC8:c.(2694-528)del. Fourteen patients had severe CHI
      demanding near-total pancreatectomy. In one patient with mild, transient neonatal
      hypoglycemia and nonautoimmune diabetes at age 11 years, no additional mutations
      were found in HNF1A, HNF4A, GCK, INS, and INSR. Retinitis pigmentosa was found in
      two patients aged 9 and 13 years. No patients had enteropathy or renal tubular
      defects. Neuromotor development ranged from normal to severe delay with epilepsy.
      CONCLUSIONS: The phenotype of Homozygous 11p15-p14 Deletion syndrome, or Usher
      CHI syndrome, includes any severity of neonatal-onset CHI and severe,
      sensorineural hearing loss. Retinitis pigmentosa and nonautoimmune diabetes may
      occur in adolescence.

PMID- 23150284
TI  - Generic medications and blood pressure control in diabetic hypertensive subjects:
      results from the REasons for Geographic And Racial Differences in Stroke
      (REGARDS) study.
AB  - OBJECTIVE: To investigate temporal improvements in blood pressure (BP) control in
      subjects with diabetes and policy changes regarding generic antihypertensives.
      RESEARCH DESIGN AND METHODS: In a cross-sectional study we used logistic
      regression models to investigate the temporal relationship between access to
      generic antihypertensive medications and BP control (<130/80 mmHg) in 5,375
      subjects (mean age, 66 +/- 9 years; 61% African American) with diabetes and
      hypertension (HTN) enrolled in the national Results from the REasons for
      Geographic And Racial Differences in Stroke (REGARDS) cohort study between 2003
      and 2007. At enrollment, BP was measured and medications in the home determined
      by medication label review by a trained professional. Generic antihypertensive
      medication status was ascertained from the U.S. Food and Drug Administration.
      RESULTS: The percentage of subjects accessing generically available
      antihypertensive medications increased significantly from 66% in 2003 to 81% in
      2007 (P < 0.0001), and the odds of achieving a BP <130/80 mmHg in 2007 was 66%
      higher (odds ratio 1.66 [95% CI 1.30-2.10]) than in 2003. Nevertheless, <50% of
      participants achieved this goal. African American race, male sex, limited income,
      and medication nonadherence were significant predictors of inadequate BP control.
      There was no significant relationship between access to generic antihypertensives
      and BP control when other demographic factors were included in the model (0.98
      [0.96-1.00]). CONCLUSIONS: Among African American and white subjects with HTN and
      diabetes, BP control remained inadequate relative to published guidelines, and
      racial disparities persisted. Although access to generic antihypertensives
      increased, this was not independently associated with improved BP control,
      suggesting that poor BP control is multifactorial.

PMID- 23150285
TI  - A simple risk stratification for time to development of sight-threatening
      diabetic retinopathy.
AB  - OBJECTIVE: The American Diabetes Association and the English NHS Diabetic Eye
      Screening Program recommend annual screening for diabetic retinopathy (DR) with
      referral to ophthalmology clinics of patients with sight-threatening DR (STDR).
      Using only longitudinal data from retinal photographs in the population-based NHS
      Diabetic Eye Screening Program in Gloucestershire, we developed a simple means to
      estimate risk of STDR. RESEARCH DESIGN AND METHODS: From 2005, 14,554 patients
      with no DR or mild nonproliferative DR only at two consecutive annual digital
      photographic screenings were categorized by the presence of DR in neither, one,
      or both eyes at each screening and were followed for a further median 2.8 years.
      RESULTS: Of 7,246 with no DR at either screening, 120 progressed to STDR,
      equivalent to an annual rate of 0.7%. Of 1,778 with no DR in either eye at first
      screening and in one eye at second screening, 80 progressed to STDR, equivalent
      to an annual rate of 1.9% and to a hazard ratio (HR) of 2.9 (95% CI 2.2-3.8)
      compared with those with no DR. Of 1,159 with background DR in both eyes at both
      screenings, 299 progressed to STDR equivalent to an annual rate of 11% and an HR
      of 18.2 (14.7-22.5) compared with individuals with no DR. CONCLUSIONS: Combining
      the results from 2 consecutive years of photographic screening enables estimation
      of the risk of future development of STDR. In countries with systematic screening
      programs, these results could inform decisions about screening frequency.

PMID- 23150288
TI  - Total spontaneous resolution by deracemization of isoindolinones.
AB  - Separated: 3-hydroxy-3-phenylisoindolin-1-ones have been resolved by dynamic
      preferential crystallization. The compounds were effectively racemized through
      ring-opening and ring-closing reactions via achiral intermediates under basic
      conditions. Crystallization from a toluene solution containing 1,8
      diazabicyclo[5.4.0]undec-7-ene (DBU) with stirring and evaporation of the solvent
      gave optically active crystals quantitatively with high ee values.

PMID- 23150287
TI  - Diagnostic and prognostic performances over 9 years of a selective screening
      strategy for gestational diabetes mellitus in a cohort of 18,775 subjects.
AB  - OBJECTIVE: We aimed to evaluate a selective screening strategy for gestational
      diabetes mellitus (GDM) based on the presence of risk factors: BMI >=25 kg/m(2),
      age >=35 years, family history of diabetes, personal history of GDM, or birth of
      a child with macrosomia. RESEARCH DESIGN AND METHODS: Of 20,630 deliveries
      between 2002 and 2010, we selected 18,775 deliveries in women with no known
      diabetes and for whom all risk factors were known. GDM was universally screened
      and defined as fasting plasma glucose level >=5.3 mmol/L and/or 2-h postload (75
      g) glucose level >=7.8 mmol/L. RESULTS: The prevalence of at least one risk
      factor has increased since 2002 (P < 0.001) from 51.7 to 61.5%, with no change in
      the GDM prevalence (mean 14.4%, intention to screen). At least one risk factor
      was present in 58.5% of women who represented 65.3% of all those with GDM. The
      presence of risk factors was significantly associated with GDM (odds ratio 1.4
      [95% CI 1.3-1.5], P < 0.001) and with GDM-related events (preeclampsia/large for
      gestational age/dystocia) (P < 0.001) with the following incidences: no GDM/no
      risk factor 8.8%, no GDM/risk factor 11.1%, GDM/no risk factor 16.7%, and
      GDM/risk factor 18.2%. CONCLUSIONS: The presence of risk factors increased during
      the last decade. This condition is predictive of GDM and GDM-related events.
      However, a selective screening would lead to missing one-third of the women with
      GDM who, even without risk factors, had more events than women without GDM.
      Therefore, these data stand against the present selective screening currently
      proposed in the French guidelines.

PMID- 23150286
TI  - Impact of sleep duration on obesity and the glycemic level in patients with type
      2 diabetes: the Fukuoka Diabetes Registry.
AB  - OBJECTIVE: Few studies are currently available regarding the influence of sleep
      duration on glycemic control in diabetic patients. The objective of the current
      study was to examine the relationship between sleep duration, obesity, and the
      glycemic level in type 2 diabetic patients. RESEARCH DESIGN AND METHODS: A total
      of 4,870 Japanese type 2 diabetic patients aged >=20 years were divided into six
      groups according to their self-reported sleep duration: less than 4.5 h, 4.5-5.4
      h, 5.5-6.4 h, 6.5-7.4 h, 7.5-8.4 h, and more than 8.5 h. The associations of
      sleep duration with obesity and the HbA(1c) levels were examined in a cross
      sectional manner. RESULTS: The HbA(1c) levels showed a quadratic association with
      sleep duration; namely, a shorter or longer sleep duration was associated with a
      higher level compared with a sleep duration of 6.5-7.4 h (P for quadratic trend
      <0.001). This association remained significant after adjusting for potential
      confounders, including the total energy intake and depressive symptoms.
      Furthermore, additional adjustments for obesity, which also showed a U-shaped
      relationship with sleep duration, did not attenuate the U-shaped sleep-HbA(1c)
      association. A significant interaction between sleep duration and age or the use
      of insulin was observed for the HbA(1c) levels. CONCLUSIONS: Sleep duration was
      shown to have U-shaped associations with obesity and the HbA(1c) levels in type 2
      diabetic patients, independent of potential confounders, and therefore may be an
      important modifiable factor for the clinical management of patients with type 2
      diabetes.

PMID- 23150290
TI  - Production of polyclonal antisera.
AB  - All immunochemical procedures require a suitable antiserum or monoclonal antibody
      raised against the antigen of interest Polyclonal antibodies are raised by
      injecting an immunogen into an animal and, after an appropriate time, collecting
      the blood fraction containing the antibodies of interest. In producing
      antibodies, several parameters must be considered with respect to the final use
      to which the antibody will be put. These include (1) the specificity of the
      antibody, i.e., the ability to distinguish between different antigens, (2) the
      avidity of the antibody, i.e., the strength of binding, and (3) the titer of the
      antibody, which determines the optimal dilution of the antibody in the assay
      system. A highly specific antibody with high avidity may be suitable for
      immunohistochemistry, where it is essential that the antibody remains attached
      during the extensive washing procedures, but may be less useful for
      immunoaffinity chromatography, as it may prove impossible to elute the antigen
      from the column without extensive denaturation.

PMID- 23150289
TI  - Application and mechanistic studies of a water-oxidation catalyst in alcohol
      oxidation by employing oxygen-transfer reagents.
AB  - By using a dimeric ruthenium complex in combination with tert-butyl hydrogen
      peroxide (TBHP) as stoichiometric oxidant, a mild and efficient protocol for the
      oxidation of secondary benzylic alcohols was obtained, thereby giving the
      corresponding ketones in high yields within 4 h. However, in the oxidation of
      aliphatic alcohols, the TBHP protocol suffered from low conversions owing to a
      competing Ru-catalyzed disproportionation of the oxidant. Gratifyingly, by
      switching to Oxone (2 KHSO(5)?KHSO(4)?K(2)SO(4) triple salt) as stoichiometric
      oxidant, a more efficient and robust system was obtained that allowed for the
      oxidation of a wide range of aliphatic and benzylic secondary alcohols, giving
      the corresponding ketones in excellent yields. The mechanism for these reactions
      is believed to involve a high-valent Ru(V)-oxo species. We provide support for
      such an intermediate by means of mechanistic studies.

PMID- 23150291
TI  - Efficient Elution of Purified Proteins from Polyvinylidene Difluoride Membranes
      (Immobilon) After Transfer from SDS-PAGE and Their Use as Immunogens.
AB  - The great analytical power of sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis (SDS-PAGE) makes it one of the most effective tools of protein
      chemistry and molecular biology. In the past, there have been many attempts to
      convert the technique from analytical to preparative scale because, by SDS-PAGE,
      one can resolve more than one hundred protein species in 5-6 h. The number of
      papers that describe preparative elution from polyacrylamide gels is immense (for
      example, see refs. 1-5), In spite of the numerous variations in the procedure of
      elution, none of the available methods is entirely satisfactory. Some of the
      methods are very laborious, and others lead to loss of resolution or poor
      recovery.

PMID- 23150292
TI  - Raising polyclonal antibodies using nitrocellulose-bound antigen.
AB  - Highly specific antibodies directed against minor proteins, present in small
      amounts in biological fluids, or against nonsoluble cytoplasmic or membraneous
      proteins, are often difficult to obtain. The main reasons for this are the small
      amounts of protein available after the various classical purification processes
      and the low purity of the proteins.

PMID- 23150293
TI  - Synthesis of peptides for use as immunogens.
AB  - An increasing problem in cell and molecular biology is the preparation of
      antibodies specific to proteins that are present in minute quantities within
      cells or tissues. With the advent of recombinant DNA technology, it is now often
      possible to deduce the primary amino acid sequence of a polypeptide without its
      purification. Two strategies then exist to raise appropriate antibodies. Either
      the gene can be expressed in a heterologous species, usually bacteria, and the
      resultant protein used as an immunogen, or alternatively, small synthetic
      peptides can be made that contain amino acid sequences inferred from that of the
      gene. Such antipeptide antibodies crossreact with the intact native protein with
      surprisingly high frequency and have the additional advantage that the epitope
      recognized by the antibody is already well defined (1). In this way, antibodies
      can be raised against novel gene products that are specifically directed against
      sites of interest, for example, unique regions, highly conserved regions, active
      sites, extracellular or intracellular domains. Moreover, the ready availability
      of the pure peptide immunogen against which the antibody was raised means that
      sera can be rapidly and easily screened, e.g., using an enzyme-linked
      immunosorbent assay (ELISA) for antipeptide activity. Free peptide can also be
      used to block antibody binding and so demonstrate immunological specificity, and
      it may be coupled to a solid support (e.g., agarose) to generate an affinity
      matrix for antibody purification.

PMID- 23150294
TI  - Production and characterization of antibodies against synthetic peptides.
AB  - Immunization protocols vary greatly between laboratories. In general, there are
      no hard and fast rules and most protocols give satisfactory results. The methods
      described below are designed to give optimal results with minimal injury to the
      test animal, and we have used them extensively and successfully for several years
      (1-5). Peptide immunizations differ from those in which the immunogen is a larger
      macromolecule in that maximal antipeptide titers (which arise rapidly after 2-3
      immunizations) do not always coincide with maximal titers against the intact
      protein (which tend to peak rather later at 4-6 immunizations). Thus, although
      antipeptide enzyme-linked immunosorbent assays (ELISAs) are useful gages of
      immune response, there is no substitute for eventual screening on the intact
      protein (e.g., by immunoprecipitation, Western blotting, and so on). Individual
      variation in antipeptide response is very marked, so it is advisable to use
      several animals (three to six) per immunogen. Rabbit responses are generally
      poorer in specific pathogen-free (SPF) animals, probably reflecting their greater
      immune naivity. Mouse responses are often best in F(1) crosses (e.g., BALB/c *
      C57B1/6) rather than pure strains. Alternatively, SJL mice generally respond
      well.

PMID- 23150295
TI  - Preparation and testing of monoclonal antibodies to recombinant proteins.
AB  - Monoclonal antibodies (MAbs) are useful, often essential, reagents for the
      isolation, identification, and cellular localization of specific gene products
      and for the determination of macromolecular structure. The ability to clone and
      sequence specific genes has revolutionized our understanding of cellular
      structure and function, and the ability to prepare recombinant proteins or to
      synthesize peptides based on protein sequences derived from cDNA clones provides
      sufficient material for generating specific antibodies. The recombinant proteins
      may be derived from prokaryotic systems, such as E. coli, or from eukaryotic
      expression systems, such as Chinese hamster ovary cells (CHO) or insect cells
      expressing constructs in baculovirus. The eucary-otic systems are being used
      increasingly for expression of glycoproteins because the recombinant material is
      glycosylated. A number of protocols will be described here that we have used
      successfully with both rat (Y3 and IR983F) and mouse (SP2/0) myelomas to generate
      MAbs to recombinant material or peptides based on cDNA sequences.

PMID- 23150296
TI  - Screening of monoclonal antibodies using antigens labeled with
      acetylcholinesterase.
AB  - The production of large quantities of monoclonal antibodies (MAbs) of
      predetermined specificity has been rendered possible by the pioneering work of
      Kohler and Milstein (1). These workers have shown that lymphocytes can be
      immortalized and subsequently cultured after somatic fusion with genetically
      selected myeloma cells. Usually, once fusion between spleen cells and myeloma
      cells has been performed, cells are suspended in a large volume of selective
      medium and distributed in culture wells, so that hybridomas are brought to clonal
      dilution. If fusion is successful, the first hybridoma colonies will be
      detectable within a few days (5-15 d). As fusion is a random process, most clones
      code for MAbs of unknown specificity, characterizing the immunological past of
      the host. It is then necessary to select the different colonies that secrete MAbs
      of the desired specificity. Owing to the great number of wells to be tested
      (often a few hundred), and to the small quantities of MAbs available (at best,
      300 uL at a few ug/mL), it is not easy at this stage to characterize the fine
      specificity of the antibodies (i.e., recognition of a precise epitope, inhibitory
      effect on a biological system, properties suitable for purifying antigen, or for
      histochemical characterization, and so on). Initially, it is generally preferable
      to use a simple method to select all the hybridomas producing MAbs directed
      against the immunizing antigen. Further characterization of these MAbs is
      performed later, after expansion of the clones.

PMID- 23150297
TI  - Purification of immunoglobulin g (IgG).
AB  - Several immunological procedures can be successfully carried out using
      nonpurified antibodies, such as unfractionated antisera, or ascitic fluid/culture
      supernatant containing monoclonal antibodies (MAbs). However, a much "cleaner"
      result can often be obtained if some form of enrichment or isolation of
      immunoglobulin is employed. Some procedures, such as conjugation with isotopes,
      fluorochromes, or enzymes, and preparation of immunoaffinity columns cannot
      usually be efficiently performed with nonpurified immunoglobulin, and some
      procedures may yield artifactual results if whole antiserum or ascitic fluid is
      used as a source of antibody. Purification of immunoglobulins is therefore
      essential or, at least, useful for a range of immunological methods. This process
      may consist of purification of total IgG or subpopulations (e.g., subclasses) of
      IgG from antisera/ascitic fluid/culture supernatant, or the isolation of a
      particular antigen binding fraction from such fluids. The former can be achieved
      by biochemical procedures, whereas the latter usually requires some form of
      affinity purification.

PMID- 23150298
TI  - Epitope mapping.
AB  - Monoclonal antibodies (MAbs) are specific immunological tools because they bind
      to a precise determinant (the epitope) on the surface of a protein. The procedure
      of identifying the binding site of a MAb is often termed "epitope mapping."

PMID- 23150299
TI  - Enzyme-antienzyme method for immunohistochemistry.
AB  - Immunohistochemical stains use antibodies to identify specific constituents in
      tissue sections. In order to detect the site of reaction, the antibody is labeled
      with an enzyme that can be reacted with a suitable substrate to give a colored
      product. The alternative is to use a fluorescent label. The advantage of an
      enzyme label is that the nuclei can be counterstained, thereby revealing the
      tissue architecture, and that the stain fades slowly, if at all, with time,
      allowing the slides to be stored.

PMID- 23150300
TI  - Double label immunohistochemistry on tissue sections using alkaline phosphatase
      and peroxidase conjugates.
AB  - One of the most common methods in immunohistochemistry involves the use of an
      antibody to the antigen of interest detected indirectly with an enzyme-labeled
      antispecies secondary antibody. The enzyme catalyzes the formation of a colored
      insoluble reaction product at the antigen site. It is possible, with careful
      choice of reagents, to label two antigens simultaneously, resulting in two
      different colored reaction products (1). Cells or tissue sections can also be
      double-labeled with two antispecies secondary antibodies carrying different
      fluorochromes (see this vol., Chapter 42 ), or by using suitable antibodies
      conjugated to different sizes of colloidal gold (see this vol., Chapter 19 ).

PMID- 23150301
TI  - Immunohistochemical detection of bromodeoxyuridine-labeled nuclei for in vivo
      cell kinetic studies.
AB  - The classical technique for identifying cells engaged in DNA synthesis is by
      their uptake of [(3)H]-thymidine, detected using autoradiography. However, this
      method can be inconvenient, as specialized darkroom and radioisotope facilities
      are required, with the potential health hazard that handling isotopes entails.
      Bromodeoxyuridine (BrdU), the halogenated 5-substituted derivative of
      deoxyuridine, is a thymidine analog specifically incorporated into the DNA of
      proliferating cells during S phase. This is now a well-established alternative to
      (3)H thymidine, since it has been shown that labeling indices for the two
      molecules are the same (1,2). The development of a monoclonal antibody (3) that
      recognizes BrdU incorporated into single-stranded DNA has resulted in several
      techniques using immunocytochemical staining to detect incorporated BrdU in
      frozen, paraffin- and plastic-embedded sections of tissue by light microscopy. It
      has also proved extremely valuable for studies in conjunction with flow cytometry
      and even, for in vivo studies of human tumor cell kinetics (see this vol.,
      Chapter 43 ). We describe here a method to detect DNA synthesis by in vivo
      labeling of nuclei with BrdU, followed by indirect immunological detection in
      paraffin-embedded tissue (4).

PMID- 23150302
TI  - Avidin-biotin technology : preparation of biotinylated probes.
AB  - During the past decade, the avidin-biotin complex has become a useful and
      versatile tool for application in a variety of biological disciplines (1-3). One
      of the major applications is in immunology and related areas (4).

PMID- 23150303
TI  - Avidin-biotin technology : preparation of avidin conjugates.
AB  - The second step required in the application of avidin-biotin technology is to
      prepare an appropriate avidin-associated probe or probes for the desired
      application (for general reviews, see refs. 1 and 2). For example, a fluorescent
      form of avidin can be used for fluorescence microscopy, fluorescence-activated
      cell sorting, and in some cases, for immunoassay. Like-wise, an avidin-enzyme
      conjugate can be used for immunoblotting, immunoassay, light microscopy, and in
      some cases, electron microscopy. An immobilized form of avidin can be used for
      isolation purposes (see Note 1).

PMID- 23150304
TI  - Immunochemical applications of avidin-biotin technology.
AB  - The major advantage in the use of avidin-biotin technology for isolation purposes
      is that an improved capacity for purification of an antigen often results (1,2).
      The antibody, bound to the column via an avidin-biotin bridge, is less affected
      by the chemistry of immobilization or by physical interactions (hydrophobic,
      electrostatic, salting-out effects, precipitation, and so on) with the solid
      support. Such potential deleterious effects are borne by avidin, which is a
      highly stable protein, and thus serves as a physicochemical buffer for the
      antibody.

PMID- 23150305
TI  - Preparation of gold probes.
AB  - Colloidal gold probes are widely used in the biological sciences for both light
      and electron microscopy. A gold probe is an electron dense sphere of gold coated
      with an immunologically active protein. There are two aspects to be considered
      when making the probe.

PMID- 23150306
TI  - Immunogold probes for light microscopy.
AB  - Light microscope immunocytochemistry was initiated by the classical work of Coons
      et al. (1,2), who developed the immunofluorescent technique for antigen
      localization. All other immunocytochemical techniques are based on the same
      philosophy, but use different microscopically dense markers. For instance,
      Avrameas and Uriel (3) and Nakane and Pierce (4) described the use of the enzyme
      peroxidase as a dense marker for immunocytochemistry, and this was later
      developed by Sternberger (5), who described the sensitive peroxidase
      antiperoxidase techniques. The initial immunoenzyme techniques have been further
      expanded by the use of alkaline phosphatase as a marker (6, see also this vol.,
      Chapter 10 ). These techniques, including the original immunofluorescent
      technique, are all routinely used for immunohistochemistry. Recently, the use of
      colloidal gold probes as immunocytochemical markers has been described for
      electron immunocytochemistry (7), and these are now proving to be of use at the
      light microscope level.

PMID- 23150307
TI  - Immunogold probes in electron microscopy.
AB  - Electron microscopy permits the detailed study of cell relationships within
      tissues and organelles within cells. Electron immunocytochemistry is the high
      resolution study of antigens within cells and their relation to cell
      ultrastructure. Fixation to achieve optimal fine structural detail for electron
      microscopy is exactly that which damages antigens with respect to reaction with
      specific antibody. Cell preparation for electron microscopy is therefore a
      compromise between retaining sufficient antigenicity while preserving the cell
      ultrastructure.

PMID- 23150308
TI  - Electron microscopic silver enhancement for double labeling with antibodies
      raised in the same species.
AB  - In immunoelectron microscopy (IEM), simultaneous labeling of two or more antigens
      on the same section is desirable for many applications. If the antibodies (Ab) to
      be used are raised in the same species, as is usually the case with monoclonal
      antibodies (MAb), the difficulty arises that the labeled secondary, antispecies
      Ab used in the first labeling step traps the primary Ab directed against the
      second antigen, thus leading to a nonspecific signal for the second antigen.

PMID- 23150309
TI  - Quantitative and qualitative immunoelectrophoresis : general comments on
      principles, reagents, equipment, and procedures.
AB  - The immunoelectrophoretic methods presented in Chapters 21 to 23 are all based on
      the electrophoretic migration of antigens in antibody-containing agarose and the
      specific immunoprecipitation of antigens with the corresponding antibodies. These
      methods exploit the property of immunoglobulins of remaining essentially
      stationary during electrophoresis at pH 8.6 (buffer pH most often used) and the
      property of most of the proteins to migrate in these conditions. Precipitating
      antibodies are required for these methods. For each antibody/antigen system, an
      individual precipitate is formed. The area enclosed by the precipitate is
      directly proportional to the concentration of antigen applied. These principles
      may, therefore, be used in a standardized procedure for immunological
      identification and quantitation of antigens and/or antibodies.

PMID- 23150310
TI  - Rocket immunoelectrophoresis technique or electroimmunodiffusion.
AB  - The rocket immunoelectrophoresis technique or electroimmunodiffusion (EID) (1) is
      a simple, fast, and reproducible technique for quantitation of a single protein,
      and is also applicable in a protein mixture. Several unknown samples can be
      analyzed on a single plate. Known reference solutions have to be included in each
      plate. To obtain an accurate quantitation, the proteins in the reference
      solutions and in the unknown samples have to be physicochemically and
      immunologically identical. The samples are applied in wells punched out of an
      agarose gel containing the corresponding monospecific antiserum. One-dimensional
      electrophoresis is performed and rocket-shaped precipitates are formed. The
      quantitation is based on measuring the height of the precipitate peak.

PMID- 23150311
TI  - Crossed immunoelectrophoresis.
AB  - Ressler first described in 1960 (1) a form of immunoelectrophoresis now called
      crossed immunoelectrophoresis (CIE) or two-dimensional immunoelectrophoresis,
      which was later improved by Laurell (2), Clarke and Freeman (3), and Weeke (4),
      among others. CIE is superior to the classical immunoelectrophoresis, according
      to Grabar and Williams (5), particularly in providing better resolution and
      quantitative capabilities. It combines the electrophoretic separation of the
      sample proteins in agarose gel with electrophoresis at right angles to the
      initial separation in an antibody-containing agarose. Each protein separated
      during the first dimension forms a separate precipitation peak during the second
      dimension. Moreover, the area under any protein peak is directly proportional to
      the concentration of that protein in the analyzed sample and inversely
      proportional to the concentration of antibody to that protein in the antiserum
      used.

PMID- 23150312
TI  - Crossed immunoaffinoelectrophoresis.
AB  - The crossed immunoaffinoelectrophoresis technique (CIAE) combines the principle
      of biospecific interaction with the principle of identification of proteins by
      immunoprecipitation in CIE. Biospecific interaction of macro-molecular components
      during electrophoresis was first described by Nakamura et al. (1). Lectins, or
      plant agglutinins, are proteins that react with carbohydrate groups with high
      specificity. Very rapidly, a combination of CIE and affinity electrophoresis with
      lectins was developed for identification and characterization of glycoproteins.
      Among the lectins, concanavalin A (Con A) is the most commonly used. Originally,
      Con A was introduced into an intermediate gel as immobilized Con A bound to
      Sepharose or free Con A (2). Glycoproteins can be partially characterized with
      respect to the number of lectin binding sites per molecule (e.g., ref. 3). Bog
      Hansen et al. (4) modified the procedure by introducing the lectin into the first
      dimension gel. Con A is electrophoretically immobile under the experimental
      conditions used for CIAE. The procedure can be used with other lectins, but their
      electrophoretic mobility must be checked beforehand. This procedure allows
      detection and separation of microheterogeneous forms of a glycoprotein. The
      degree of retardation during the first dimension electrophoresis in the gel with
      lectin is an expression of the affinity between the glycoprotein and the lectin.
      Higher affinity means stronger binding, which in turn means a higher degree of
      retardation.

PMID- 23150313
TI  - Immunodetection of proteins by Western blotting.
AB  - The technique of protein immunoblotting, more commonly known as "Western"
      blotting, was first described a decade ago by Towbin et al., (1), using electric
      current to transfer polypeptides from polyacrylamide gels to nitrocellulose,
      although several groups had previously reported the use of capillary forces to
      effect the transfer of DNA ("Southern" blotting [2]), RNA ("Northern" blotting [3
      5]), and protein (6,7) from agarose and polyacrylamide gels.

PMID- 23150314
TI  - Erasable Western blots.
AB  - Western blotting (reviewed in 1-3; see also this vol., Chapter 24 ) refers to
      formation and detection of an antibody-antigen complex between an antibody and a
      polypeptide that is immobilized on derivatized paper. Most commonly, polypeptides
      in a complex mixture are separated by electrophoresis through polyacrylamide gels
      in the presence of sodium dodecylsulfate (SDS), electrophoretically transferred
      to thin sheets of nitrocellulose or nylon, and reacted sequentially with one or
      more antibody-containing solutions. This sequence of manipulations can be
      utilized to determine whether a polypeptide recognized by a specific antiserum is
      present in a particular biological sample (cell type, subcellular fraction, or
      biological fluid), to follow the purification of the polypeptide, or to assess
      the location of epitopes within the polypeptide during chemical or enzymatic
      degradation. Alternatively, the same series of manipulations can be utilized to
      determine whether antibodies that recognize a particular polypeptide are
      detectable in a sample of biological fluid. Since Western blotting takes
      advantage of the power of electrophoresis for separating complex mixtures of
      polypeptides, it is possible to derive large amounts of information from this
      technique without necessarily purifying the antigen being studied.

PMID- 23150315
TI  - Colloidal gold staining and immunoprobing on the same Western blot.
AB  - Proteins, blotted from polyacrylamide gels onto nitrocellulose sheets (Western
      Blots) can be stained nonspecifically with a variety of dyes, or they can be
      identified individually by probing with appropriate antibodies. These procedures
      may be performed on duplicate blots, staining the total protein pattern on one
      blot and using the second blot for the immune reaction (1,2). This chapter
      describes how to combine both methods on one blot, i.e., staining the blot first
      for total protein, followed by an indirect immune reaction (3).

PMID- 23150316
TI  - Colloidal gold staining and immunodetection in 2-d protein mapping.
AB  - This chapter extends the use of the technique described in the previous chapter
      to two-dimensional (2D) protein gels, as well as containing some alternatives and
      modifications to the method.

PMID- 23150317
TI  - Fluorescent protein staining on nitrocellulose with subsequent immunodetection of
      antigen.
AB  - The transfer of proteins from gels to nitrocellulose or other immobilizing
      matrices has become increasingly popular as a powerful tool for the subsequent
      analysis of proteins. Most frequently, the blotted proteins are analyzed for
      their antigenic properties by Western blotting.

PMID- 23150318
TI  - Competitive ELISA.
AB  - Enzyme-linked immunosorbent assay (ELISA) is a very useful technique for the
      specific and sensitive assay of certain compounds, in which suitable antibodies,
      monoclonal or polyclonal, to the compounds are available. The technique has found
      particular application in the monitoring of environmental contaminants and
      toxins, either studying the primarily contaminated materials, e.g., foodstuffs,
      or body fluids of potentially exposed humans. The technique has been increasingly
      applied to monitoring the carcinogenic mycotoxins, the aflatoxins.

PMID- 23150319
TI  - Twin-Site ELISAs for fos and myc Oncoproteins Using the AMPAK System.
AB  - Twin-site ELISA is a simple technique for quantitation of specific proteins in
      cell or tissue extracts. The application of this method to fos and myc
      oncoproteins is described. There are two basic procedures: 1. Extraction of fos
      and myc proteins from biological material in a form suitable for immunoassay. 2.
      Determination of the amount of fos or myc protein in the extract by ELISA using
      specific antibodies, one of which is conjugated to alkaline phosphatase (AP) and
      is detected by the AMPAKTM amplifier system.

PMID- 23150320
TI  - Preparation of cytotoxic antibody-toxin conjugates.
AB  - Conjugates of antibodies with plant toxins, such as ricin and abrin, are potent
      cytotoxic agents that selectively eliminate target cells from mixed cell cultures
      in vitro, and have great promise as antitumor agents in cancer therapy (1). Ricin
      and abrin are protein toxins consisting of two different polypeptide subunits,
      the A and B chains, which are of similar size (between 30 and 34 kDa) and are
      joined by a single disulfide bond. The A chain is a ribosome-inactivating protein
      (RIP) that inactivates eukaryotic ribosomes by a specific irreversible covalent
      modification of the ribosomal RNA (2). The B chain binds to cell surface
      galactose-containing oligosaccharide residues. Following receptor-mediated
      endocytosis of toxin bound to the cell surface, the A chain gains access to the
      cytosol and destroys the ability of the cell to make protein (3).

PMID- 23150321
TI  - Immunoaffinity purification and quantification of antibody-toxin conjugates.
AB  - Cytotoxic antibody-toxin conjugates made using antibodies and ribs some
      inactivating proteins (RIPs) are prepared using chemical crosslinking methods
      (1,2 and this vol., Chapter 31 ). Gel permeation chromatography is used as a
      first step to purify conjugate molecules from the reaction mixture. This
      procedure removes protein aggregates, the excess of RIP employed in the
      conjugation reaction, and low molecular weight byproducts. However, a significant
      fraction of the resulting conjugate preparation consists of unconjugated antibody
      that cannot be completely separated from the conjugate on the basis of size
      discrimination alone (see chapter 31 ).

PMID- 23150322
TI  - An immuno-slot-blot assay for detection and quantitation of alkyldeoxyguanosines
      in DNA.
AB  - The detection and quantitation of DNA adducts plays a central role in the
      determination of dose-response relationships for chemical carcinogens, mutagens,
      and chemotherapeutic agents in experimental laboratory investigations.
      Furthermore, it serves in molecular dosimetry and risk estimation of humans
      chronically exposed to environmental carcinogens, and of cancer patients
      undergoing treatment with alkylating cytostatic drugs (1,2). These investigations
      require sensitive methods that do not necessitate the administration of
      radioactively labeled compounds.

PMID- 23150323
TI  - Production of monoclonal antibodies for the detection of chemically modified DNA.
AB  - Monoclonal antibodies that are specific for sites of base modification in DNA
      have a number of applications in, for example, studies of carcinogenesis, drug
      action, or DNA repair (1). The production of antibodies of the appropriate
      specificity entails practical considerations that are specific to this type of
      antigen.

PMID- 23150324
TI  - Sensitive competitive enzyme-linked immunoassay for quantitation of modified
      bases in DNA.
AB  - A widely used configuration for competitive enzyme-linked immunosorbent assay
      (ELISA) of modified regions in polymeric DNA involves competition between a
      standardized quantity of antigen bound to the assay well and a variable quantity
      and/or quality of antigen in solution. These are competing for a limited
      standardized quantity of antibody in solution. The amount of antibody that binds
      to the immobilized antigen is measured and expressed as a percentage of the
      amount that binds in the absence of competing dissolved antigen. In this
      situation the amount of immobilized antigen is not generally known, but this is
      of no consequence, the essential feature being that the amount is highly uniform
      from well to well (see ref. 1 for a treatise on enzyme immunoassays).

PMID- 23150325
TI  - An Immunochemical Assay for Detecting Transition of B-DNA to Z-DNA.
AB  - The enzyme immunoassay technique described below is a simple and sensitive method
      to detect left-handed Z-DNA formation in synthetic polynucleotides, recombinant
      plasmids, and native DNAs. This method utilizes the differences in the antigenic
      properties of right-handed B-DNA and left-handed Z-DNA.

PMID- 23150326
TI  - Cell sorting using immunomagnetic beads.
AB  - Immunomagnetic beads are uniform, polymer particles coated with a polystyrene
      shell that provides both a smooth hydrophobic surface to facilitate physical
      absorption of molecules, such as antibodies, and surface hydroxyl groups that
      allow covalent chemical binding of other bioreactive molecules, such as
      streptavidin, lectins, and peptides. Iron (III) oxide (Fe(2)O(3)) deposited in
      the core gives the beads superparamagnetic properties that lead to consistent and
      reproducible reactions to a magnetic field without permanent magnetization of the
      particles. These are the two qualities on which immunomagnetic separation (IMS)
      depends.

PMID- 23150327
TI  - Cell preparation for flow cytometry.
AB  - For flow cytometry, a suspension of single cells, free of large clumps and excess
      debris, is essential. The quality of the data obtained depends as much on the
      quality of the preparation as on that of the flow cytometer.

PMID- 23150328
TI  - Preparation of rat lung cells for flow cytometry.
AB  - Morphologically, the lung is a complex organ containing over 40 different cell
      types (1). Although species and strain dependent, in the Fischer rat, the most
      common cell types include: endothelial, 33%; Type I, 6.5%; Type II, 12%;
      macrophages, 8%; ciliated and nonciliated bronchiolar epithelial (Clara) cells,
      1.3 and 0.7%, respectively (2,3). The lungs from an "adult" rat comprise about 4
      * 10(8) cells (3). Unlike the liver, there is no one enzyme, such as collagenase,
      universally used for cell dispersion. Instead, a wide variety of proteases, such
      as Protease I or XIV (4,5), have been recommended. Enzyme cocktails have often
      been adjusted to suit the cell type being isolated: e.g.,
      collagenase/trypsin/elastase for Type I cells (6), elastase/trypsin for Type II
      cells (7), and hyaluronidase/cytochalasin for tracheal epithelial cells (8).
      However, such proteolytic enzymes may lead to the loss of specific cell surface
      markers. There is general agreement that DNAse is necessary to minimize cellular
      reaggregation once the lung cells have been isolated. This procedure describes
      the use of the proteolytic enzyme subtilisin, recently introduced for the
      isolation of lung cells (9), which has been particularly effective in the
      preparation of functional Clara cells following their separation by flow
      cytometry (10). Type II cells have also been isolated using similar procedures
      (unpublished), and macrophages are lavaged from the lung during the perfusion
      process and can be recovered if required.

PMID- 23150329
TI  - The isolation of rat hepatocytes for flow cytometry.
AB  - The isolation and subsequent study of hepatocytes in in vitro conditions was
      first transformed by Berry and Friend (1), who developed a collagenase liver
      perfusion method, allowing the isolation of large numbers of cells with high
      viability.

PMID- 23150330
TI  - Flow cytometric analysis of cells using an antibody to a surface antigen.
AB  - Identifying a subset of cells, particularly peripheral blood lymphocytes, by
      means of a fluorescently-tagged antibody is one of the commonest applications of
      flow cytometry. There are many methods, all of them basically similar, for
      labeling antigens on cell surfaces. Two slightly different procedures are given
      in this chapter; these can be adapted to meet most needs.

PMID- 23150331
TI  - Multiple immunofluorescence analysis of cells using flow cytometry.
AB  - Prior to 1982, the measurement of more than one antigen simultaneously by flow
      cytometry required two lasers-an argon-ion laser to excite fluorescein (at 488
      nm) and a krypton or a dye laser to excite rhodamine or one of its derivatives.
      The discovery of a naturally occurring fluorochrome, phycoerythrin (PE), changed
      this (1). PE is a phycobiloprotein found in red algae. It can be excited
      efficiently at 488 nm (simultaneously with fluorescein) and has a peak
      fluorescence at 578 nm, sufficiently removed from the peak of 520 nm from
      fluorescein. There is some overlap in the emission spectra from the two dyes (in
      particular, there is still some emission from fluorescein above 580 nm) and this
      must be corrected, either electronically or by the computer software.

PMID- 23150332
TI  - Cell kinetic studies using a monoclonal antibody to bromodeoxyuridine.
AB  - The study of cell kinetics has traditionally involved the use of radioactive
      precursors of DNA, such as tritiated thymidine ((3)HTdR), and autoradiography to
      detect their incorporation into DNA. These techniques have provided detailed
      knowledge of cell kinetics in both in vitro and in vivo experimental systems. The
      technique, however, is time consuming and arduous and is not readily applicable
      to human tumor research because of ethical problems involved in incorporation of
      a radioisotope into DNA.

PMID- 23150333
TI  - Production and use of nonradioactive hybridization probes.
AB  - Molecular hybridization is a useful technique for identifying specific target
      sequences even when they are present as a single copy in a complex population. It
      can be performed either on a solid matrix on which pure DNA (or RNA) is bound
      (blot hybridization) or on tissue sections (in situ hybridization). Until
      recently, the probes used in hybridization were usually labeled with
      radioisotopes. However, the short half-life, disposal, and safety problems of
      radioactive probes stimulated the development of nonradioactive hybridization
      techniques. In these, the probes are labeled with nonradioactive reporter
      molecules, which can be haptens, proteins, digoxigenin, biotin, and so forth.
      These reporter molecules can then be detected by enzyme-labeled antibodies or
      streptavidin (in the case of biotinylated probes). Of these reporter molecules,
      biotin and digoxigenin have several advantages over the others because of their
      small size. Therefore, they minimally interfere with hybridization efficiency. In
      addition, the high affinity of the binding of biotin and streptavidin (K ( d ) =
      10(-15) M) is almost equivalent to covalent bonds. In fact, the biotin system was
      the first nonradioactive hybridization technique sensitive enough for routine use
      on Mot hybridization (1) and in situ hybridization (2).

PMID- 23150334
TI  - Cellular human and viral DNA detection by nonisotopic in situ hybridization.
AB  - In situ hybridization may be defined as the detection of nucleic acids in situ in
      cells, tissues, chromosomes, and isolated cell organelles. The technique was
      described in 1969 by two separate groups, who demonstrated repetitive ribosomal
      sequences in nuclei of Xenopus oocytes using radiolabeled probes (1,2).
      Refinements in recombinant DNA technology and the development of nonisotopic
      probe labeling and detection obviate the need for radiation protection and
      disposal facilities, and have converted nonisotopic in situ hybridization (NISH)
      from a purely research technique to one that can be used in routine laboratory
      testing.

PMID- 23150335
TI  - Chromosomal mapping of genes by nonisotopic in situ hybridization.
AB  - With the advent of nonradioactive labels, in situ hybridization (ISH) has become
      a useful technique for the detection of viral DNA in infected tissue (1), mRNA
      expression (2), sex determination (3), human gene mapping (4), and interphase
      cytogenetics (5-8). For chromosomal mapping of genes by ISH, labeled DNA probe is
      hybridized to metaphase spreads. If the label is a radioisotope, the signal is
      detected by autoradiography (9). Nonradioactive labels, such as biotin (4),
      digoxigenin (10), or 2-acetylaminofluorene (AAF), are detected by
      immunocytochemistry. AAF is incorporated by chemical modification of the DNA
      probe. Biotin and digoxigenin are incorporated enzymatically by nick translation
      or by random primer extension (11), although both can be incorporated by chemical
      modification (12). In the authors' laboratory, biotin has been successfully used
      in mapping genes with probes of 0.8 Kb (10). The method described here,
      therefore, applies to biotin-labeled probes although, with minor modifications,
      can be adapted to probes labeled by digoxigenin or AAF. An example of chromosomal
      mapping of a unique sequence is shown in Fig. 1. Fig. 1. Human chromosome spread
      probed with a biotdnylated beta-globin probe. There is a signal at band pl.5
      (arrow) on chromosome 11.

PMID- 23150336
TI  - Nonisotopic in situ hybridization : immunocytochemical detection of specific
      repetitive sequences on chromosomes and interphase nuclei.
AB  - The term in situ hybridization describes a wide range of techniques concerned
      with the detection of DNA or RNA sequences within individual cells, tissues, or
      on identifiable regions of chromosomes. The technique utilizes an ability to
      label DNA or RNA probes so that, following hybridization with complementary
      sequences in the target tissues, the labeled DNA or RNA can be detected by
      various techniques.

PMID- 23150337
TI  - Biotinylated probes in colony hybridization.
AB  - Colony hybridization is a procedure that allows the detection of cells containing
      nucleic acid sequences of interest (1). In this method, microbial colonies grown
      on, or transferred to, a supporting membrane are lysed and their nucleic adds
      denatured to single strands and fixed in place on the membrane. The membrane is
      then exposed to a similarly denatured "probe" sequence, which is identical or
      homologous to all or part of the target sequence, under conditions favoring
      reannealling. Probe sequences hybridize to complementary sequences on the
      membrane. Positive hybridization events are then detected by determining the
      presence and location of probe sequences on the membrane.

PMID- 23150338
TI  - Screening of lambdagt11 cDNA Libraries Using Monoclonal Antibodies.
AB  - The screening of a lambdagt11 library with monoclonal antibodies described here
      is a relatively uncomplicated procedure, but it requires a little introduction
      nevertheless. For simplicity, it is assumed that you have in your possession a
      library that is ready to screen, i.e., either a library bought from a company or
      a library that you have made. Construction of a lambdagt11 library is described
      in Volume 4, Chapter 19 .

PMID- 23150339
TI  - Expression of foreign genes in Mammalian cells using an antibody fusion system.
AB  - Whereas the expression of foreign genes in mammalian cells usually proves
      successful, the purification of gene products is often a difficult and time
      consuming process. The availability of monoclonal antibodies to the foreign
      protein can greatly assist in small scale purification, but where antibodies are
      not available, alternatives have to be sought One useful approach involves the
      fusion of the foreign gene adjacent to a gene segment encoding an antibody heavy
      chain variable region (1). By transfection of this construct into a cell line
      producing a compatible light chain or by cotransfection of the fusion product
      with a light chain gene, an antibody-like molecule can be produced and purified
      using the corresponding antigen.

PMID- 23150340
TI  - Interactions between the tumor suppressor p53 and immune responses.
AB  - PURPOSE OF REVIEW: The p53 tumor suppressor is a master regulator of antitumor
      defenses through its control of growth arrest, senescence and apoptosis. In
      recent years, p53 regulation was found to extend to a variety of biological
      processes including autophagy, fertility, metabolism and immune responses. Here,
      we focus on the role of p53 in the immune system. We explore the relationship
      between p53 and the innate immune response with particular emphasis on the Toll
      like receptor (TLR) pathway and implications for cancer therapy. RECENT FINDINGS:
      Numerous studies have shown that the immune system, especially innate immunity,
      has a critical role in tumor development. It appears that p53 can influence
      innate immune responses as part of its tumor suppressor activities and recent
      work suggests that the complete set of innate immune TLR genes are responsive to
      chromosomal stress and the transcriptional network regulated by p53. Activation
      of p53 by common antitumor agents results in p53 dependent regulation of
      expression of most TLR genes in human primary and cancer cell lines, resulting in
      modulation of TLR downstream responses to cognate ligands. In addition several
      tumor-associated p53 mutants can also affect TLR gene expression. These
      observations together with the discovery of other immune-related p53 target genes
      provide new insights into the relationship between p53 and immunity and suggest
      approaches that might be useful in cancer therapies. SUMMARY: The tumor
      suppressor p53 can modulate innate immune gene responses in response to factors
      that can activate p53. This is expected to provide new opportunities in cancer
      diagnosis and in chemotherapeutic strategies that employ specific TLR agonists or
      antagonists that target the TLR pathway.

PMID- 23150341
TI  - Targeting the hallmarks of cancer:  towards a rational approach to next
      generation cancer therapy.

PMID- 23150342
TI  - Synucleins: are they two-edged swords?
AB  - The synuclein family consists of three distinct highly homologous genes, alpha
      synuclein, beta-synuclein, and gamma-synuclein, which have so far been found only
      in vertebrates. Proteins encoded by these genes are characterized by an acidic C
      terminal region and five or six imperfect repeat motifs (KTKEGV) distributed
      throughout the highly conserved N-terminal region. Numerous data demonstrate that
      synucleins are implicated in two groups of the most devastating human disorders,
      i.e., neurodegenerative diseases (NDDs) and cancer. Mutations in the alpha
      synuclein gene are associated with familial forms of Parkinson's disease (PD),
      and accumulation of alpha-synuclein inclusions is a hallmark of this disorder. In
      breast cancer, increased expression of gamma-synuclein correlates with disease
      progression. Conversely, some results indicate that the members of the synuclein
      family may have a protective effect. How might these small proteins combine such
      controversial properties? We present evidence that synuclein's features are
      basically regulated by two mechanisms, i.e., posttranslational modifications
      (PTMs) and the level of their expression. We also discuss a new, emerging area of
      investigation of synucleins, namely, their role in the cell-to-cell propagation
      of pathology.

PMID- 23150343
TI  - Posterolateral capsular release for correction of valgus deformity.
AB  - Achieving coronal balance during arthroplasty of a valgus knee presents a
      challenge for the surgeon. Various techniques for lateral release had been
      described with no consensus among surgeons. We retrospectively reviewed 42
      consecutive patients (38 women, mean age 72.7 years, follow-up 42 +/- 23 months)
      with a valgus deformity who were operated while using a posterolateral capsular
      release as the sole method of lateral release. All knees were successfully
      balanced, without the need for further release of other structures. Valgus angles
      improved from 17.5 +/- 4.6 degrees (range 11 to 31) to 6.3 +/- 2.2 degrees (range
      2 to 11) (p < 0.0001), and the knee and functional scores improved from 5.4 +/-
      17.7 and 24.8 +/- 24.7 to 88.2 +/- 15.8 and 70 +/- 30, respectively (p < 0.0001)
      at last follow-up. One patient developed transient peroneal palsy after
      correction of severe deformity. The posterolateral capsule release, which is
      similar to that of the "inside-out" technique, provides a simple and safe
      solution for balancing a valgus knee.

PMID- 23150345
TI  - Unicompartmental knee arthroplasty: factors influencing the outcome.
AB  - Currently, the outcome and indications of unicompartmental knee arthroplasty
      (UKA) are still controversial. We retrospectively reviewed a consecutive case
      series of UKA done by a single surgeon between 2004 and 2007 including 178 knees
      (140 patients). There were 31 lateral UKA and 147 medial UKA. With a minimum
      follow-up of 24 months (average 54 months) in 159 knees (other 19 knees were lost
      to follow-up at 3 to 18 months after surgery), 6 knees (3.8%, all medial UKA)
      were converted to total knee arthroplasty in 17 to 66 months (average 33 months).
      We found that the outcome of UKA was not influenced by the patient's age, body
      mass index, or early degeneration in the patellofemoral joint (PFJ). Compared
      with other reports, there was a greater proportion of lateral UKA in our series
      (17.4%). Although lateral UKA showed a trend toward less complications and
      implant failure compared with medial UKA, WOMAC scores (Western Ontario and
      McMaster Universities Osteoarthritis Index) were similar between the two types of
      partial knee arthroplasty. Our results indicate that young age, obesity, and
      early degeneration in the PFJ may not be contraindications to UKA, and lateral
      UKA functions as well as, if not better than medial UKA. However, a long-term
      follow-up is required to confirm these findings.

PMID- 23150346
TI  - Correction of proximal tibia varus with external fixation.
AB  - Correction of proximal tibia varus deformity has been used with success. Our
      Protocol is to use monolateral frame to correct varus of less than 10 degrees and
      to use the Taylor spatial frame for deformities greater than 10 degrees and for
      multiplanar deformities. Is this protocol successful? Ninety-one limbs in 68
      patients with proximal tibia varus were treated with percutaneous proximal tibial
      osteotomy and external fixation. The monolateral and spatial frames were used for
      36 and 55 limbs, respectively. Each group was further subdivided into neutral or
      intentionally overcorrected subgroups. Monolateral group time of correction and
      time in frame was 15 days (8 to 20) and 101 days (81 to 133), respectively. The
      preoperative mechanical axis deviation (MAD) was 22 mm medial (10 to 44).
      Postoperative MAD in the neutral subgroup was 5 mm lateral (2 to 10) and 3 mm
      medial (0 to 7). Postoperative MAD in the overcorrected subgroup was 10 mm
      lateral (4 to 20) and one patient was 5 mm medial. Medial proximal tibial angle
      (MPTA) improved from 85 degrees (79 to 89) to 90 degrees (85 to 96) in the
      neutral group and to 92 degrees (85 to 98) in the overcorrected group. Spatial
      frame group time of correction and time in frame was 34 days (7 to 99) and 130
      days (95 to 177), respectively. The preoperative MAD was 40 mm medial (range 5 to
      155). This improved to 5 mm medial (0 to 30) and 4 mm lateral (0 to 7) in the
      neutral group, and 17 mm medial (0 to 35) and 11 mm lateral (4 to 28) in the
      overcorrection group. MPTA improved from 80 degrees (40 to 87) to 88 degrees (83
      to 96) in the neutral group and to 84 degrees (89 to 97) in the overcorrected
      group. In both groups, there was no significant change in the ankle or knee range
      of motion. There was one refracture in both groups. Our algorithm for treating
      proximal tibial varus deformities is safe and effective. For simple varus
      deformities, we recommend use of the monolateral frame. We reserve the use of the
      spatial frame for large or complex deformity correction.

PMID- 23150347
TI  - Testing of double-stranded allografts used in ACL reconstruction.
AB  - We used bovine tibiae and two-stranded human anterior tibialis tendon grafts to
      compare biomechanical properties of two tibial fixation devices, the Milagro
      Interference Screw (Milagro) and the Bio-Intrafix Soft Tissue Tibial Fixation
      System (Bio-Intrafix). A total of 24 constructs (12 with each type of fixation)
      underwent biomechanical testing with 12 matched constructs undergoing uniaxial
      loading to failure (rate of 1 mm/sec) and the other 12 matched constructs
      undergoing cyclic loading (10,000 cycles at 1 Hz with a loading range of 125 to
      375 N). All constructs failed by slippage of one or both ends of the anterior
      tibialis graft past the fixation device. One of the six Bio-Intrafix specimens
      failed before 10,000 cycles; four of the six Milagro specimens failed before
      10,000 cycles. Bio-Intrafix, which is designed for a four-stranded graft,
      provided superior fixation to a traditional bioabsorbable interference screw in a
      two-stranded soft tissue graft at one of the weakest links in anterior cruciate
      ligament reconstruction surgery.

PMID- 23150348
TI  - Results of medial retinacular imbrication in patients with unilateral patellar
      dislocation.
AB  - Many surgical methods are used for treating malaligned patella after patellar
      dislocation, but one surgical method may not be appropriate for all patients. The
      purpose of this study was to determine the radiographic and subjective outcomes
      of patients who underwent imbrication of redundant medial structures. A total of
      42 patients met the inclusion criteria of suffering a traumatic, unilateral
      patellar dislocation and had no J-sign, no patella alta, asymmetry on Merchant
      view radiograph with normal patella alignment on the noninvolved side, and MRI
      showing injury to the medial retinaculum. Patients were prospectively evaluated.
      A total of 38 patients (mean age 19.2 years) completed follow-up evaluations at a
      mean of 31.7 months postoperatively. Mean congruence angle improved from 19.7
      degrees  preoperatively to 5.4 degrees  postoperatively (p < 0.001) and was not
      statistically significantly different than the noninvolved knee of 4.1 (p =
      0.5194). The mean linear displacement measurement improved from 6.0 mm
      preoperatively to 1.6 mm postoperatively (p < 0.001) and was not statistically
      significantly different than the noninvolved knee of 1.4 mm (p = 0.6294). Total
      33 of 38 patients (87%) returned to their preinjury activity level including
      sports. Three patients had recurrence of patellar dislocation after surgery while
      playing sports. For patients who have the specific indications for imbrication of
      the medial retinaculum, surgery can be successful for re-establishing normal
      patellofemoral alignment and restoring function.

PMID- 23150344
TI  - Femoral tunnel malposition in ACL revision reconstruction.
AB  - The Multicenter Anterior Cruciate Ligament (ACL) Revision Study (MARS) group was
      formed to study a large cohort of revision ACL reconstruction patients. The
      purpose of this subset analysis study of the MARS database is to describe
      specific details of femoral tunnel malposition and subsequent management
      strategies that surgeons chose in the revision setting. The design of this study
      is a case series. The multicenter MARS database is compiled from a questionnaire
      regarding 460 ACL reconstruction revision cases returned by 87 surgeons. This
      subset analysis described technical aspects and operative findings in
      specifically those cases in which femoral tunnel malposition was cited as the
      cause of primary ACL reconstruction failure. Of the 460 revisions included for
      study, 276 (60%) cases cited a specific "technical cause of failure." Femoral
      tunnel malposition was cited in 219 (47.6%) of 460 cases. Femoral tunnel
      malposition was cited as the only cause of failure in 117 cases (25.4%). Surgeons
      judged the femoral tunnel too vertical in 42 cases (35.9%), too anterior in 35
      cases (29.9%), and too vertical and anterior in 31 cases (26.5%). Revision
      reconstruction involved the drilling of an entirely new femoral tunnel in 91
      cases (82.1%). For primary reconstruction, autograft tissue was used in 82 cases
      (70.1%). For revision reconstruction, autograft tissue was used in 61 cases
      (52.1%) and allograft tissue in 56 cases (47.9%). Femoral tunnel malposition in
      primary ACL reconstruction was the most commonly cited reason for graft failure
      in this cohort. Graft selection is widely variable among surgeons.

PMID- 23150349
TI  - Suture repair versus arrow repair for symptomatic meniscus tears of the knee: a
      systematic review.
AB  - A healthy meniscus is important for normal function of the knee. Numerous studies
      support that the repair of a torn meniscus is important to prevent degenerative
      changes in the knee. The ability to repair torn menisci is based on several
      factors including location, tear orientation, chronicity, and concomitant
      ligamentous knee injuries. In this systematic review, meniscal repair technology
      is evaluated. Specifically, the retear rates are compared between the arrow
      repair and the suture repair techniques. After searching three databases (PubMed,
      Cochrane Central Register of Controlled Trials, and Embase) and reviewing annual
      meeting abstracts from the American Orthopaedic Society for Sports Medicine (2005
      to 2010), four studies (two observational and two randomized controlled trials)
      were selected for this systematic review. Due to the limited study number and
      variability between studies (study design, sample population, outcome measures,
      and surgical technique), a meta-analysis was not performed. The overall quality
      of the literature was poor and thus conclusions are limited. No clear superiority
      of one technique was determined by this review.

PMID- 23150350
TI  - Knee sports injury is associated with an increased prevalence of unilateral knee
      replacement: a case-controlled study.
AB  - Injury to the knee during athletics is common and may limit future sports
      participation, but its long-term effects on patients are less well characterized.
      Examining the development of end-stage osteoarthritis (OA) in these patients may
      help better clarify this relationship. We hypothesize that sports-related knee
      injuries are associated with subsequent unilateral knee OA and need for total
      knee arthroplasty (TKA) relative to bilateral knee replacement. We present a
      single-hospital case-control study of 124 consecutive patients undergoing primary
      TKA over a 6-month period for end-stage OA. Patients were interviewed at the time
      of surgery using a standardized questionnaire to detect and characterize a
      history of athletic knee injury. The presence of contralateral knee arthritis
      based on preoperative assessment was noted for all patients. A control population
      was derived from patients with diagnosed or known bilateral OA undergoing TKA.
      Patients were all assessed for exposure to earlier sports or athletic injury.
      Prestudy power analysis and uni- and multivariate statistical analyses were
      performed. Of the 124 patients, 27 (22%) recorded a history of athletic knee
      injury. Evidence of bilateral significant knee OA was found in 73 patients and
      unilateral arthritis in 51 patients. Patients with unilateral OA were found to
      have an increased likelihood of previous athletic injury relative to those with
      bilateral disease (odds ratio: 6.08, p = 0.0001). There is a significant
      prevalence of sports-related injuries in patients with unilateral knee OA. This
      study suggests that patients with such injuries may develop arthritis via a
      different process, sports-related trauma, than patients with bilateral
      nontraumatic OA.

PMID- 23150351
TI  - Effect of flexion and rotation on measures of coronal alignment after TKA.
AB  - Attainment of a neutral mechanical axis is one of the primary goals in total knee
      arthroplasty (TKA). The accuracy of the procedure is evaluated by measuring the
      hip-knee-ankle angle (HKAA) on long leg radiographs. Rotation of the lower limb
      and knee flexion could possibly affect the HKAA measured on plain radiographs. In
      this study, a TKA was performed on a saw-bone model of the lower limb. Long leg
      radiographs from the femoral head to the ankle were obtained after sequentially
      varying the alignment of the knee model in 5-degree increments of flexion and
      rotation, from 0 to 20 degrees. Flexion or external rotation alone, up to 20
      degrees changed the HKAA by no more than 1 degree. A combination of flexion and
      external rotation progressively altered the HKAA. The HKAA was altered by 5
      degrees at a combination of 15- or 20-degree flexion and 20-degree external
      rotation. While flexion or external rotation alone had little effect on the HKAA,
      a combination of the two altered it substantially.

PMID- 23150352
TI  - Is there an association between chronicity of patellar instability and
      patellofemoral cartilage lesions? An arthroscopic assessment of chondral injury.
AB  - The purpose of this study was to investigate the association between chronicity
      of patellar instability on the prevalence, grade, and location of chondral
      lesions in patients with recurrent patellar instability. Patellofemoral chondral
      status was documented and graded according to the Outerbridge classification in
      38 patients who underwent arthroscopic examination at the time of a medial
      patellofemoral ligament reconstruction procedure. Chondral lesions of any
      location were observed in 63.2% of patients. Patellar and trochlear lesions were
      observed in 57.9 and 13.2% of patients, respectively. There was a significantly
      higher duration of patellar instability in patients with a trochlear lesion
      versus those without a trochlear lesion (p < 0.01), and in patients with combined
      patellar and trochlear lesions versus those without both patellar and trochlear
      lesions (p < 0.01). There was a significant correlation between chronicity of
      patellar instability and Outerbridge grade of trochlear chondral injury (p =
      0.01). Chi-squared analysis revealed that chronicity of patellar instability
      greater than 5 years was significantly associated with the likelihood of
      trochlear lesions (p < 0.05). We conclude that patients with increasing
      chronicity of patellar instability may have a higher likelihood of and higher
      grade of patellofemoral chondral injuries, specifically for trochlear lesions.

PMID- 23150353
TI  - Improvement in quality of life with use of an unloader knee brace in active
      patients with OA: a prospective cohort study.
AB  - The purpose of this study was to determine if short form (SF)-12 physical
      component would increase with unloader brace use. Patient expectations and
      predictors of significant improvement were determined. Our hypothesis was that
      patients with unloader braces will have increases in general physical health (SF
      12) and function (Western Ontario and McMaster Universities Arthritis Index
      [WOMAC]). Patients were enrolled in institutional review board-approved
      prospective cohort study. They completed a self-administered questionnaire (SF
      12; WOMAC, Tegner activity scale, expectations) at enrollment, 3 weeks, 6 weeks,
      and 6 months. In this study, 39 patients, 23 males and 16 females (average age =
      61 years [range 44 to 87]), were prescribed an unloader brace. Patients had
      significant improvement in quality of life (SF-12) (p < 0.05). There was
      significant improvement in pain, stiffness, and function (WOMAC) (p < 0.05).
      Patients who reported Tegner of 3 or greater at final follow-up had significantly
      higher SF-12 physical component (48 vs. 37; p = 0.023). Return to recreational
      sports was very important in 83% and somewhat important in 17%. Improving ability
      to walk was very important in 89%. Pain relief was very important in 69%,
      somewhat important in 17%. Of these, 39% expected most pain to be relieved and
      57% expected all pain to be relieved. The most important expectations were to
      have confidence in knee (97% very important), avoid future knee degeneration (90%
      very important), and improve ability to maintain general health (93% very
      important). Patients demonstrated a significant decrease in pain and disability.
      Patients saw improvement in SF-12 physical component. Braces specifically
      designed to unload the degenerative compartment of the knee can be an effective
      treatment to decrease pain and maintain activity level to increase overall
      physical health.

PMID- 23150354
TI  - MI TKA: a risk factor for early revision surgery.
AB  - Minimal incision total knee arthroplasty (MI TKA) was developed with the
      potential to decrease surgical trauma, pain, and recovery time. While this
      procedure has increased in popularity, some surgeons have questioned its safety
      and long-term efficacy. In this study 58 consecutive revision total knee
      arthroplasties (TKAs) (57 patients) performed at one academic medical center from
      2006 to 2008 are reviewed. Prospectively collected clinical and radiographic data
      included: incision length, gender, age, time to revision surgery, and primary
      diagnosis at time of revision. Of these, 34 knees involving infection and
      rerevision were excluded. Of the remaining 24 knees, 11 knees that met inclusion
      criteria had undergone MI TKA. There were no differences between the groups with
      regard to age, diagnosis, body mass index, and gender. Average time to revision
      was shorter for the MI TKA patients (29 vs. 65 months, p < 0.032, odds ratio
      14.7). Reasons for revision were aseptic loosening (55%), pain/stiffness (27%),
      malrotation (9%), and instability (9%) in the MI TKA group and aseptic loosening
      (53%), instability (15%), pain/stiffness (8%), malrotation (8%), combined
      malrotation and instability (8%), and polyethylene wear/osteolysis (8%) in the
      traditional TKA group. These data suggest that MI TKA may be a risk factor for
      early revision.

PMID- 23150355
TI  - Posteromedial corner injury in knee dislocations.
AB  - Surgeons are often faced with very limited data available to make informed
      decisions regarding the appropriate treatment of patients with posteromedial
      corner (PMC) injuries of the knee. This study compared the outcomes of surgical
      repair versus reconstruction in knee dislocation patients who have sustained
      injury to the PMC of the knee. Senior author treated 113 consecutive knee
      dislocations with 115 PMC injuries over 7 years. A total of 71 knee dislocation
      patients with 73 PMC tears qualified for the study and were followed for a mean
      of 43 months. Patients who had a PMC repair were assigned to treatment Group A.
      Group B included patients who had autograft reconstruction of the PMC. Patients
      who had an allograft PMC were assigned to Group C. A total of 25 patients had a
      repair, with 5 failures (20%), whereas 48 patients had reconstruction of the PMC
      with 2 failures (4%). There was a significant difference between the failure rate
      of PMC repairs and PMC reconstructions. Reconstruction of the PMC using a
      technique that reestablishes the critical triangle of the medial collateral
      ligament, the posterior oblique ligament, and the semitendinosus yielded better
      stability than repair in patients with a knee dislocation that included PMC
      instability.

PMID- 23150356
TI  - Photoelectrocatalysis to improve cycloreversion quantum yields of photochromic
      dithienylethene compounds.
AB  - An open and shut case: photoirradiation of the 9-mesityl-10-methylacridinium ion,
      which acts as a photoredox catalyst, evoked catalytic cycloreversion of the
      photochromic 1,2-dithienylethene (DTE) compounds with one order of magnitude
      enhancement in quantum yields. Mechanistic studies revealed that the back
      electron transfer and electron transfer from the neutral closed form of DTE
      compounds to the open-form radical cation are key steps.

PMID- 23150357
TI  - Identification and analysis of inherited retinal disease genes.
AB  - Inherited retinal diseases display a very high degree of clinical and genetic
      heterogeneity, which poses challenges in identifying the underlying defects in
      known genes and in identifying novel retinal disease genes. Here, we outline the
      state-of-the-art techniques to find the causative DNA variants, with special
      attention for next-generation sequencing which can combine molecular diagnostics
      and retinal disease gene identification.

PMID- 23150358
TI  - Mouse models for studies of retinal degeneration and diseases.
AB  - Mouse models, with their well-developed genetics and similarity to human
      physiology and anatomy, serve as powerful tools with which to investigate the
      etiology of human retinal degeneration. Mutant mice also provide reproducible,
      experimental systems for elucidating pathways of normal development and function.
      Here, I describe the tools used in the discoveries of many retinal degeneration
      models, including indirect ophthalmoscopy (to look at the fundus appearance),
      fundus photography and fluorescein angiography (to document the fundus
      appearance), electroretinography (to check retinal function), as well as the
      heritability test (for genetic characterization).

PMID- 23150359
TI  - Retinal fundus imaging in mouse models of retinal diseases.
AB  - The development of in vivo retinal fundus imaging in mice has opened a new
      research horizon, not only in ophthalmic research. The ability to monitor the
      dynamics of vascular and cellular changes in pathological conditions, such as
      neovascularization or degeneration, longitudinally without the need to sacrifice
      the mouse, permits longer observation periods in the same animal. With the
      application of the high-resolution confocal scanning laser ophthalmoscopy in
      experimental mouse models, access to a large spectrum of imaging modalities in
      vivo is provided.

PMID- 23150360
TI  - Functional phenotyping of mouse models with ERG.
AB  - In many situations it is important to be able to assess the degree of retinal
      function, e.g., for the characterization of mouse models with unknown retinal
      involvement, when studying degenerative processes, for the analysis of visual
      signal processing, and during the follow-up of therapeutic interventions. Full
      field electroretinography (ERG), yielding a sum response of event-related
      transient electrical activity of the entire retina to light stimulation, is
      widely applied in human as well as experimental functional diagnostics. ERG
      examinations normally include initial dark-adapted (scotopic) measurements that
      enable rod-driven activity to be studied, followed by light-adapted (photopic)
      recordings to obtain information about cone system contributions. The results
      allow the correlation of acute or long-term disease-related changes or their
      alleviation by therapy with morphological data, in order to obtain a
      comprehensive understanding of the underlying processes and mechanisms.

PMID- 23150361
TI  - Phenotyping of mouse models with OCT.
AB  - Optical coherence tomography (OCT) is an invaluable technique to perform
      noninvasive retinal imaging in small animal models such as mice. It provides
      virtual cross sections that correlate well with histomorphometric data with the
      advantage that multiple iterative measurements can be acquired in time line
      analyses to detect dynamic changes and reduce the amount of animals needed per
      study.

PMID- 23150362
TI  - Light damage as a model of retinal degeneration.
AB  - The induction of retinal degeneration by light exposure is widely used to study
      mechanisms of cell death. The advantage of such light-induced lesions over
      genetically determined degenerations is that light exposures can be manipulated
      according to the needs of the experimenter. Bright white light exposure can
      induce a synchronized burst of apoptosis in photoreceptors in a large retinal
      area which permits to study cellular and molecular events in a controlled
      fashion. Blue light of high energy induces a hot spot of high retinal irradiance
      within very short exposure durations (seconds to minutes) and may help to unravel
      the initial events after light absorption which may be similar for all damage
      regimens. These initial events may then induce various molecular signaling
      pathways and secondary effects such as lipid and protein oxidation, which may be
      varying in different light damage setups and different strains or species,
      respectively. Blue light lesions also allow to study cellular responses in a
      circumscribed retinal area (hot spot) in comparison with the surrounding
      tissue.Here we describe the methods for short-term exposures (within the hours
      range) to bright full-spectrum white light and for short exposures (seconds to
      minutes) to high-energy monochromatic blue or green light.

PMID- 23150363
TI  - N-methyl-D-aspartate (NMDA)-mediated excitotoxic damage: a mouse model of acute
      retinal ganglion cell damage.
AB  - The animal model of N-methyl-D-aspartate (NMDA)-induced excitotoxic damage of
      retinal ganglion cells (RGC) is widely used to study the molecular mechanisms of
      RGC apoptosis and/or its prevention by neuroprotective agents. This chapter
      provides protocols for applying NMDA-induced excitotoxic damage to RGC of mouse
      eyes and for subsequent measuring of the extent of the resulting damage.

PMID- 23150364
TI  - Generation of transgenic X. laevis models of retinal degeneration.
AB  - Transgenic models are invaluable tools for researching retinal degenerative
      disease mechanisms. However, they are time-consuming and expensive to generate
      and maintain. We have developed an alternative to transgenic rodent models of
      retinal degeneration using transgenic Xenopus laevis. We have optimized this
      system to allow rapid analysis of transgene effects in primary transgenic
      animals, thereby providing an alternative to establishing transgenic lines, and
      simultaneously allowing rigorous comparisons between the effects of different
      transgenes.

PMID- 23150365
TI  - Analysis of photoreceptor degeneration in the zebrafish Danio rerio.
AB  - Disturbances in the general mRNA metabolism have been recognized as a major
      defect in a growing number of hereditary human diseases. One prominent example of
      this disease group is Retinitis pigmentosa (RP), characterized by selective loss
      of photoreceptor cells. RP can be caused by dominant mutations in key factors of
      the pre-mRNA processing spliceosome. In these cases, the complex events leading
      to the RP phenotype can only insufficiently be analyzed in rodents or other model
      organisms due to the essential functions of these splice factors. Here we
      introduce the zebrafish Danio rerio as a valuable vertebrate model system to
      study RP and related diseases.

PMID- 23150366
TI  - Analysis of optokinetic response in zebrafish by computer-based eye tracking.
AB  - Large-field movements in the visual surround trigger spontaneous, compensatory
      eye movements known as optokinetic response (OKR) in all vertebrates. In
      zebrafish (Danio rerio) the OKR is well developed at 5 days post fertilization
      and can be used in the laboratory for screening of visual performance following
      genetic manipulations or pharmaceutical treatments. Several setups for
      measurement of the zebrafish OKR have been described. All of them are based on
      the presentation of moving gratings to the larva or to the adult fish. However,
      they differ in the way of presenting gratings and in the method of analysis.
      Here, we describe a detailed protocol for our newest software that enables
      computer-generation of the moving stripes and automatic tracking of eye movement.
      This protocol makes it possible to quantitatively measure OKR in both larvae and
      adult fishes in a fast and reliable way.

PMID- 23150367
TI  - Analysis of the Drosophila compound eye with light and electron microscopy.
AB  - The Drosophila compound eye is a regular structure, in which about 750 units,
      called ommatidia, are arranged in a highly regular pattern. Eye development
      proceeds in a stereotypical fashion, where epithelial cells of the eye imaginal
      discs are specified, recruited, and differentiated in a sequential order that
      leads to the highly precise structure of an adult eye. Even small perturbations,
      for example in signaling pathways that control proliferation, cell death, or
      differentiation, can impair the regular structure of the eye, which can be easily
      detected and analyzed. In addition, the Drosophila eye has proven to be an ideal
      model for studying the genetic control of neurodegeneration, since the eye is not
      essential for viability. Several human neurodegeneration diseases have been
      modeled in the fly, leading to a better understanding of the function/misfunction
      of the respective gene. In many cases, the genes involved and their function are
      conserved between flies and human. More strikingly, when ectopically expressed in
      the fly eye some human genes without a Drosophila counterpart can induce
      neurodegeneration, detectable by aberrant phototaxis, impaired electrophysiology,
      or defects in eye morphology. These defects are often rather subtle alteration in
      shape, size, or arrangement of the cells, and can be easily scored at the
      ultrastructural level. This chapter aims to provide an overview regarding the
      analysis of the retina by various means.

PMID- 23150368
TI  - Cell-specific markers for the identification of retinal cells by
      immunofluorescence microscopy.
AB  - Identification and visualization of specific cells and cellular structures in the
      retina are fundamental for understanding the visual process, retinal development,
      disease progression, and therapeutic intervention. The increased usage of
      transgenic and naturally occurring mutant mice has further emphasized the need
      for retinal cell-specific imaging. Immunofluorescence microscopy of retinal
      cryosections and whole mount tissue labeled with cell-specific markers has
      emerged as the method of choice for identifying specific cell populations and
      mapping their distribution within the retina. In most cases indirect labeling
      methods are employed in which lightly fixed retinal samples are first labeled
      with a primary antibody targeted against a cell-specific protein of interest and
      then labeled with a fluorescent dye-tagged secondary antibody that recognizes the
      primary antibody. The localization and relative abundance of the protein can
      readily be imaged under a conventional fluorescent or confocal scanning
      microscope. Immunofluorescence labeling can be adapted for imaging more than one
      protein antigen through the use of multiple antibodies and different,
      nonoverlapping fluorescent dyes. A number of well-characterized immunochemical
      markers are now available for detecting photoreceptors, bipolar cells, amacrine
      cells, horizontal cells, Muller cells, and retinal pigment epithelial cells in
      the retina of mice, and other mammals.

PMID- 23150369
TI  - A method of horizontally sliced preparation of the retina.
AB  - Various types of retinal neurons, including amacrine, ganglion, and horizontal
      cells, expand neurites (dendrites or axons) in horizontal direction and make
      synaptic or electrical contacts with other cells to integrate the visual
      information. Many types of ion-channels and receptors are located along these
      neurites, and these horizontal connections critically contribute to the
      information processing in the retinal circuits. However, many of previous
      electrophysiological and immunocytochemical studies employed slice preparations
      cut by vertical direction in which most of these cells and their neurites were
      severely damaged and removed. This might lead to the underestimation of active
      and passive conductance in horizontally expanding neurites, and also missing of
      morphological information of horizontal structures. Here, we describe an
      alternative slicing method of horizontally cut preparation of the retina. The
      slice is made horizontally at the inner layer of the retina using a vibratome
      slicer after the retina is embedded in the low-temperature melting agarose gel.
      This horizontal slice preparation enables us to directly access cells in the
      inner retina by patch-clamp recording, calcium imaging, single RT-PCR, and
      immunocytochemistry. The method described here would offer an alternative
      strategy for studying the functions of neurons and neural circuits in the retina.

PMID- 23150370
TI  - Detection of DNA fragmentation in retinal apoptosis by TUNEL.
AB  - Terminal dUTP nick end labeling (TUNEL) is an invaluable technique used in the
      study of late-stage apoptosis. The technique is based upon detection of
      fragmented DNA, a well-recognized characteristic of apoptosis, usually with
      fluorescent markers. Here, we describe the TUNEL technique (1) employing two
      different detection techniques, fluorescence microscopy and fluorescence
      activated cell sorting (2) which can be applied to the analysis of apoptosis in
      retinal tissues or retinal cell cultures, respectively.

PMID- 23150371
TI  - High-throughput RNA in situ hybridization in mouse retina.
AB  - The introduction of large-scale gene expression profiling studies has greatly
      increased the need to rapidly obtain high-quality cellular expression patterns of
      genes found to exhibit differential expression. The use of large-scale
      nonradioactive RNA in situ hybridization makes this possible, and greatly
      increases the general usefulness of this data. Here, we describe protocols for
      parallel analysis of up to 50 different gene-specific probes in mouse retinal
      sections.

PMID- 23150372
TI  - Assessment of mitochondrial damage in retinal cells and tissues using
      quantitative polymerase chain reaction for mitochondrial DNA damage and
      extracellular flux assay for mitochondrial respiration activity.
AB  - Mitochondrial dysfunction and genomic instability are associated with a number of
      retinal pathologies including age-related macular degeneration, diabetic
      retinopathy, and glaucoma. Consequences of mitochondrial dysfunction within cells
      include elevation of the rate of ROS production due to damage of electron
      transport chain proteins, mitochondrial DNA (mtDNA) damage, and loss of metabolic
      capacity. Here we introduce the quantitative polymerase chain reaction assay
      (QPCR) and extracellular flux assay (XF) as powerful techniques to study
      mitochondrial behavior. The QPCR technique is a gene-specific assay developed to
      analyze the DNA damage repair response in mitochondrial and nuclear genomes. QPCR
      has proved particularly valuable for the measurement of oxidative-induced mtDNA
      damage and kinetics of mtDNA repair. To assess the functional consequence of
      mitochondrial oxidative damage, real-time changes in cellular bioenergetics of
      cell monolayers can be measured with a Seahorse Biosciences XF24 analyzer. The
      advantages and limitations of these procedures will be discussed and detailed
      methodologies provided with particular emphasis on retinal oxidative stress.

PMID- 23150373
TI  - Analysis of photoreceptor rod outer segment phagocytosis by RPE cells in situ.
AB  - Counting rhodopsin-positive phagosomes residing in the retinal pigment epithelium
      (RPE) in the eye at different times of day allows a quantitative assessment of
      engulfment and digestion phases of diurnal RPE phagocytosis, which efficiently
      clears shed photoreceptor outer segment fragments (POS) from the neural retina.
      Comparing such activities among age- and background-matched experimental wild
      type and mutant mice or rats serves to identify roles for specific proteins in
      the phagocytic process. Here, we describe experimental procedures for mouse eye
      harvest, embedding, sectioning, immunofluorescence labeling of rod POS phagosomes
      in RPE cells in sagittal eye sections, imaging of POS phagosomes in the RPE by
      laser scanning confocal microscopy, and POS quantification.

PMID- 23150374
TI  - Ca2+ microfluorimetry in retinal Muller glial cells.
AB  - Calcium acts as a prominent second messenger in virtually every cell type and
      modulates a plethora of cell functions. Thus, Ca(2+) microfluorimetry became a
      valuable tool to assess information about mechanisms involved in the regulation
      of the intracellular calcium level in research on living tissues. Here we offer
      insight into distinct approaches to detect changes in calcium levels specifically
      in Muller cells, the principal macroglial cells of the retina.

PMID- 23150375
TI  - Functional analysis of retinal microglia and their effects on progenitors.
AB  - The identification of stem/progenitor cells within the retinal neural environment
      has opened up the possibility of therapy via cellular replacement and/or
      reprogramming of resident cell populations. Within the neuro-retinal niche,
      following injury or in disease states (including inflammation and degeneration),
      cellular responses affect tissue homeostasis, reduce cell density, disrupt tissue
      architecture, and produce scar formation. Microglia (resident retinal immune cell
      tissue macrophage) are key to the maintenance of retinal homeostasis and are
      implicated in responses that may influence the control and behavior of retinal
      progenitors. Factors to consider in the generation of a transplantable cell
      resource with good migratory and integrative capacity include their yield,
      purity, and functional viability. Utilizing human postmortem retina, we have
      created a research platform to isolate, culture, and characterize adult retinal
      microglia as well as analyze their effect on retinal progenitors. Here, we
      describe techniques using magnetic labeled bead cell separation to isolate pure
      populations of retinal CD133(+) precursor cells and CD11b(+) microglia from
      primary adult retinal cell suspensions (RCSs), enabling flow cytometric cell
      phenotypic and qPCR genotypic analysis, as well as functional analysis by real
      time ratiometric calcium imaging.

PMID- 23150376
TI  - Analysis of photoreceptor outer segment phagocytosis by RPE cells in culture.
AB  - Retinal pigment epithelial (RPE) cells are among the most actively phagocytic
      cells in nature. Primary RPE and stable RPE cell lines provide experimental model
      systems that possess the same phagocytic machinery as RPE in situ. Upon
      experimental challenge with isolated photoreceptor outer segment fragments (POS),
      these cells promptly and efficiently recognize, bind, internalize, and digest
      POS. Here, we describe experimental procedures to isolate POS from porcine eyes
      and to feed POS to RPE cells in culture. Furthermore, we describe three different
      and complementary methods to quantify total POS uptake by RPE cells and to
      discriminate surface-bound from engulfed POS.

PMID- 23150377
TI  - Ca2+-imaging techniques to analyze Ca2+ signaling in cells and to monitor
      neuronal activity in the retina.
AB  - Ca(2+) is an important regulator of many cell functions including proliferation,
      apoptosis, movements, secretion, contraction, excitation, and differentiation.
      The regulation of these different cell functions is encoded by the specific
      temporal and spatial distribution of Ca(2+) signals. In degenerative diseases
      mutations can lead to changes in cell functions in the worst case to apoptosis.
      Thus analysis of signals arising as changes in intracellular free Ca(2+)
      represent an important step towards the understanding of mutation-dependent or
      environmental impact into cell function. The classic approach to study changes in
      intracellular free Ca(2+) is the measurement of intracellular Ca(2+) by using
      Ca(2+)-sensitive fluorescence dyes in conjunction with fluorescence microscopy as
      a method called Ca(2+) imaging. In this chapter the basic method and a short
      theoretical background will be provided to perform Ca(2+)-imaging experiments. As
      a model cultured retinal pigment epithelial cells will be used. The basic steps
      of the method are the loading of the cells with the fluorescence dye by
      incubation with a membrane permeable ester of the dye. The next step would be the
      application of an agonist which can be further analyzed by blockers of enzymes or
      by manipulating the different Ca(2+)-storing compartments which contribute to
      changes in intracellular free Ca(2+). At the end of an experiment an on-cell type
      of calibration will be performed to calculate the underlying concentration of
      intracellular free Ca(2+). Furthermore, the successful calibration of an
      experiment can be used as a measure of a reliable experiment. In addition to
      that, three examples for basic experiments will be given which can lead to a
      first insight into the mechanism underlying changes in cytosolic free Ca(2+)as a
      second messenger.

PMID- 23150378
TI  - Double chromatin immunoprecipitation: analysis of target co-occupancy of retinal
      transcription factors.
AB  - Combinatorial binding of transcription factors (TFs) and cofactors to specific
      regulatory regions of target genes in vivo is an important mechanism of
      transcriptional regulation. Chromatin immunoprecipitation (ChIP) is a powerful
      technique to detect protein binding to specific regions of target genes in vivo.
      However, conventional ChIP analysis for individual factors (single ChIP) does not
      provide information on co-occupancy of two interacting TFs on target genes, even
      if both bind to the same chromatin regions. Double ChIP analysis involves
      sequential (double) immunoprecipitation of two chromatin-binding proteins and can
      be used to study co-occupancy of two or more factors on specific regions of the
      same DNA allele. Furthermore, by including a cell type-specific protein in double
      ChIP, target co-occupancy in a specific cell type can be studied even if the
      other partner is more widely expressed. In this chapter, we describe a detailed
      protocol for double ChIP analysis in mouse retinas. Using the rod-specific
      transcription factor NR2E3 and the cone/rod homeobox protein CRX as examples, we
      show that NR2E3 and CRX are co-enriched on the promoter of active Rho and Rbp3
      genes in rods, but are present to a much lesser degree on the promoters of silent
      cone opsin genes. These results suggest a new mechanism by which rod and cone
      genes are differentially regulated by these transcription factors in rod
      photoreceptors.

PMID- 23150379
TI  - Quantifying the activity of cis-regulatory elements in the mouse retina by
      explant electroporation.
AB  - Transcription factors control gene expression by binding to noncoding regions of
      DNA known as -cis-regulatory elements (CREs; i.e., enhancer/promoters).
      Traditionally, cis-regulatory analysis has been carried out via mouse
      transgenesis which is time-consuming and nonquantitative. Electroporation of DNA
      reporter constructs into living mouse tissue is a rapid and effective alternative
      to transgenesis which permits quantitative assessment of cis-regulatory activity.
      Here, we present a simple technique for quantifying the activity of photoreceptor
      specific CREs in living explanted mouse retinas.

PMID- 23150380
TI  - Optimized technique for subretinal injections in mice.
AB  - Subretinal injections in mice become increasingly important. Currently, the most
      prominent application is in gene therapy of inherited eye diseases by means of
      viral vector delivery to photoreceptors or the retinal pigment epithelium (RPE).
      Since there are no large animal models for most of these diseases, genetically
      modified mouse models are commonly used in preclinical proof-of-concept studies.
      However, because of the relatively small mouse eye, adverse effects of the
      subretinal delivery procedure itself may interfere with the therapeutic outcome.
      The protocol described here concerns a transscleral pars plana subretinal
      injection in small eyes, and may be used for but not limited to virus-mediated
      gene transfer.

PMID- 23150381
TI  - Adeno-associated viral vectors for gene therapy of inherited retinal
      degenerations.
AB  - Adeno-associated virus (AAV) vectors are in wide use for in vivo gene transfer
      for the treatment of inherited retinal disease. AAV vectors have been tested in
      many animal models and have demonstrated efficacy with low toxicity. In this
      chapter we describe some of the recent methods for small-scale production of
      these vectors for use in a laboratory setting in volumes and purity appropriate
      for testing in small and large animals.

PMID- 23150382
TI  - Barrier modulation in drug delivery to the retina.
AB  - The inner blood-retina barrier (iBRB) is essential in restricting the movement of
      systemic components such as enzymes, anaphylatoxins, or pathogens that could
      otherwise enter the neural retina and cause extensive damage. The barrier has
      evolved to confer protection to the delicate microenvironment of the retina, and
      the tight junctions located between adjacent microvascular endothelial cells can
      restrict the passage of up to 98% of clinically validated low-molecular-weight
      therapeutics which could hold significant promise for a range of degenerative
      retinal conditions. Here, we describe a method for the selective RNAi-mediated
      targeting of one component of the tight junction, claudin-5. We outline the
      generation of a doxycycline inducible adeno-associated viral vector for the
      localized, inducible, and size-selective modulation of the iBRB and describe how
      this vector can be used in ophthalmology research.

PMID- 23150383
TI  - Synthesis of imides by palladium-catalyzed C-H functionalization of aldehydes
      with secondary amides.
AB  - An efficient palladium-catalyzed C-H functionalization of aldehydes with various
      N-substituted N-heteroarene-2-carboxamides has been developed for the synthesis
      of secondary imides. The reaction tolerates various functionalities, such as
      methoxy, fluoro, chloro, and bromo groups. A tentative radical mechanism for a
      Pd(II)/Pd(IV) catalytic cycle is proposed.

PMID- 23150384
TI  - The diverse functions of germline P-granules in Caenorhabditis elegans.
AB  - P-granules are conserved cytoplasmic organelles, similar to nuage, that are
      present in Caenorhabditis elegans germ cells. Based on the prevailing sterility
      phenotype of the component mutants, P-granules have been seen as regulators of
      germ cell development and function. Yet, specific germline defects resulting from
      P-granule failure vary, depending on which component(s) are inactivated, at which
      stage of development, as well as on the presence of stress factors during animal
      culture. This review discusses the unifying themes in many P-granule functions,
      with the main focus on their role as organizing centers nucleating RNA regulation
      in the germ cell cytoplasm.

PMID- 23150385
TI  - Catalytic [4+2] cyclization of alpha,beta-unsaturated acyl chlorides with 3
      alkylenyloxindoles: highly diastereo- and enantioselective synthesis of
      spirocarbocyclic oxindoles.
AB  - Cinchona alkaloids were used as Lewis base catalysts in the title reaction. The
      [4+2] cyclization of alpha,beta-unsaturated acyl chlorides with electron
      deficient alkenes derived from oxindole gave the corresponding spirocarbocyclic
      oxindoles.

PMID- 23150387
TI  - Identification of legionella in the environment.
AB  - Legionella is ubiquitous in freshwater systems worldwide and can also be found in
      soil. Legionellosis may be caused by inhalation of aerosolized water or soil
      particles containing Legionella. Isolation of Legionella from the environment is
      an essential step in outbreak investigation and may also be performed within the
      context of a hazard analysis and control risk management plan. Culture remains
      the gold standard for detection of Legionella in environmental samples. Specific
      properties of environmental sites that could be a source of Legionella
      contamination, collection of samples from such sites, and procedures for culture
      of these samples for Legionella are described in this chapter.

PMID- 23150386
TI  - TGF-beta/BMP signaling pathway is involved in cerium-promoted osteogenic
      differentiation of mesenchymal stem cells.
AB  - The extensive applications of cerium (Ce) increased the chance of human exposure
      to Ce and its compounds. It was reported that Ce was mainly deposited in the bone
      after administration. However, the potential effect and mechanism of Ce on bone
      metabolism are not well understood. In this study, we investigated the cellular
      effects of Ce on the differentiation of mesenchymal stem cells (MSCs) and the
      associated molecular mechanisms. The results indicated that Ce promoted the
      osteogenic differentiation and inhibited the adipogenic differentiation of MSCs
      at cell level. Genes involved in transforming growth factor-beta/bone
      morphogenetic proteins (TGF-beta/BMP) signaling pathway were significantly
      changed when the MSCs were exposed to 0.0001 uM Ce by RT(2) ProfilerTM PCR Array
      analysis. The expression of genes and proteins related to pathways, osteogenic,
      and adipogenic biomarkers of MSCs upon interaction with Ce was further confirmed
      by quantitative real-time reverse transcriptase polymerase chain reaction (Q-PCR)
      and Western blot analysis. The results suggest that Ce exerts the effects by
      interacting with bone morphogenetic protein receptor (BMPR) and activates TGF
      beta/BMP signaling pathway, leads to the up-regulation of the osteogenic master
      transcription factor, runt-related transcription factor 2 (Runx 2), and the down
      regulation of the adipocytic master transcription factor, peroxisome proliferator
      activated receptor gamma 2 (PPARgamma2). Runx2, which subsequently up-regulates
      osteoblast (OB) marker genes collagen I (Col I) and BMP2 at early stages,
      alkaline phosphatase (ALP), and osteocalcin (OCN) at later stages of
      differentiation, thus driving MSCs to differentiate into OBs. The results provide
      novel evidence to elucidate the mechanisms of bone metabolism by Ce.

PMID- 23150389
TI  - Sequence-based identification of legionella.
AB  - Legionella strains are considered biologically inert with respect to traditional
      identification schemes. Various phenotypic alternatives have been attempted but
      all have lacked resolution as additional species have been added to what is
      proving to be a large genus. Only sequence-based schemes have the required
      resolution to confidently speciate or recognize potentially novel strains. The
      mip gene target is the most comprehensive currently available, with the added
      advantage of a Web-based analysis tool. Other gene targets are available for most
      if not all species, the best of which target 16S rRNA, rpoB, rnpB, or proA genes.
      One or several of these should be used to confirm important strains or clarify
      apparent novelness. The increased resolution of these sequence-based schemes has
      recognized many new species, and many more remain to be characterized. I provide
      a mip analysis of 44 such strains along with the recognized species, and a
      SplitsTree network analysis of recognized species and 20 novel strains for which
      sequence for the five targets is available.

PMID- 23150388
TI  - Identification of legionella in clinical samples.
AB  - Currently, several methods are used for the detection of Legionella in clinical
      samples, and these methods constitute part of the criteria for defining
      legionellosis cases. Urinary antigen detection is the first-line diagnostic test,
      although this test is limited to L. pneumophila serogroup 1 (Lp1) (Helbig et al.,
      J Clin Microbiol 41:838-840, 2003). The use of molecular techniques can improve
      Legionaire's disease (LD) diagnosis by detecting other serogroups and species
      (Diederen et al., J Clin Microbiol 46:671-677, 2008). The isolation of Legionella
      strains from pulmonary samples by axenic culture is still required to perform
      further epidemiological investigations (Blyth et al., N S W Public Health Bull
      20:157-161, 2009; Fields et al., Clin Microbiol Rev 15:506-526, 2002) but
      demonstrates various sensitivities. Amoebic coculture has been described as a
      method to recover Legionella from clinical culture-negative specimens (La Scola
      et al., J Clin Microbiol 39:365-366, 2001; Rowbotham, J Clin Pathol 36:978-986,
      1983) and can be proposed for optimizing Legionella strain isolation from samples
      contaminated by oropharyngeal flora. Identification of Legionella isolates is
      based on serological characterization, genotypic methods (with sequencing of the
      mip gene as the standard method) and, more recently, the Matrix-assisted laser
      desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) method.This
      chapter is limited to the identification of Legionella in clinical samples;
      antibody detection in human serum will not be discussed.

PMID- 23150390
TI  - Investigation of outbreaks: epidemiology.
AB  - Outbreaks of Legionnaires' disease create high levels of public anxiety and media
      interest and inevitably consume a great deal of public health resources.
      Investigations should begin as early as possible in order to rapidly identify
      suspected sources of infection, control the outbreak and prevent further cases
      occurring. The investigations should be coordinated by an outbreak control team
      who work collaboratively within local/national/international public health
      guidelines and with clear terms of reference. The actions carried out by
      epidemiologists when investigating community-, hospital-, or travel-associated
      outbreaks are comprehensively outlined in this chapter. The microbiological and
      environmental actions that complement this work are discussed in the accompanying
      chapters.

PMID- 23150391
TI  - Outbreak investigations and identification of legionella in contaminated water.
AB  - To avoid further cases arising from an infectious source it is essential to
      ensure the early identification of all potential source(s) within an identified
      area, or buildings, to determine if they are being managed safely; to take
      appropriate samples and ensure appropriate remedial actions are taken to remove
      the risk of further cases. If samples are to give representative results of the
      system at the time of sampling it is essential to ensure that they are processed
      appropriately using methods which are both sensitive and specific. It is also
      imperative that results are interpreted in context and transmitted as soon as
      possible to the outbreak control team to ensure appropriate and timely action is
      taken on sites which still pose a risk of infection. A multidisciplinary team
      approach and forward planning are essential to ensure that there are sufficiently
      trained and competent personnel and resources. Recognition of sources is
      dependent on many factors including thorough epidemiological investigations to
      narrow down the potential geographical area or water system that maybe common to
      the patients as agreed within the outbreak case definition. qPCR can be useful in
      both the elimination and identification of suspect systems/sites. However, it
      requires expert interpretation of results in the context of the sample site and
      factors which may affect the results such as the use of biocides together with
      the use of an algorithm for interpretation and actions to be taken to put the
      results in context.

PMID- 23150392
TI  - Typing methods for legionella.
AB  - In this chapter we describe the methods currently used for subgrouping Legionella
      pneumophila and other non-pneumophila species. In the first part we describe
      monoclonal antibody (mAb) subgrouping, either by indirect immunofluorescence or
      indirect ELISA methods. These monoclonal antibodies are not commercially
      available but can be obtained for noncommercial purposes from one of the authors.
      Further, we describe pulsed-field gel electrophoresis (PFGE), amplified fragment
      length polymorphism (AFLP) and sequence-based typing (SBT) as well standardized
      and reproducible methods for genotyping. The SBT schema is currently available
      for L. pneumophila whereas PFGE and AFLP can be used for all Legionella species.
      For certain applications it might be useful to use spoligotyping to distinguish
      strains belonging to the same sequence type (ST).

PMID- 23150393
TI  - Culturing, media, and handling of legionella.
AB  - This chapter describes methods for culturing Legionella pneumophila in both
      complex and defined media. The first protocol describes the use of buffered
      charcoal yeast extract (BCYE) agar, the solid medium that is most commonly used
      for culturing L. pneumophila. The next procedure details the cultivation of L.
      pneumophila in buffered yeast extract (BYE) broth, i.e., the liquid medium
      version of BCYE agar. We describe how culturing in BYE broth can also be used for
      investigating proteins that are secreted by the type II secretion system of L.
      pneumophila. The next part of the chapter explains the cultivation of L.
      pneumophila in a chemically defined liquid media (CDM). CDM contains a mixture of
      amino acids, metals, alpha-ketoglutarate, and pyruvate. Because of its defined
      nature, CDM provides a simple means for controlling the concentration of
      nutrients and thereby allows for investigations of physiology and metabolism. To
      illustrate this point, the use of deferrated CDM for the purpose of assessing
      Legionella siderophore production is outlined. Finally, the chapter ends with a
      brief discussion of the storage and shipping of L. pneumophila.

PMID- 23150394
TI  - The intracellular metabolism of legionella by isotopologue profiling.
AB  - Metabolic pathways and fluxes can be analyzed under in vivo conditions by
      incorporation experiments using general (13)C-labeled precursors. On the basis of
      the isotopologue compositions in amino acids or other metabolites, the
      incorporation rates of the supplied precursors and the pathways of their
      utilization can be studied in considerable detail. In this chapter, the method of
      isotopologue profiling is illustrated with recent work on the metabolism of
      intracellular living Legionella pneumophila.

PMID- 23150395
TI  - Induction of competence for natural transformation in Legionella pneumophila and
      exploitation for mutant construction.
AB  - Many Gram-positive and Gram-negative bacteria possess natural competence
      mechanisms for DNA -capture and internalization that play an important role in
      diversifying adaptation of bacteria through horizontal gene transfer. Natural
      transformation and other mechanisms of horizontal gene transfer are dependent on
      DNA recombination. Natural competence can be exploited both for studying
      adaptation and horizontal gene transfer as well as for genetic engineering of a
      strain. We report here different approaches to measure competence on solid and in
      liquid media by using a reporter plasmid where GFP is fused to the comEA gene or
      by inducing competence and measuring transformability induced by DNA-damaging
      stress. Finally we describe a method where competence is induced through a
      combined temperature and aeration shift, which may be exploited for the
      construction of mutants in Legionella pneumophila. This approach seems to be less
      prone to the appearance of secondary mutations during mutant construction as
      compared to procedures using electroporation.

PMID- 23150396
TI  - Constructing unmarked gene deletions in Legionella pneumophila.
AB  - The ability to construct recombinant alleles efficiently in strains of interest,
      particularly unmarked deletions that reduce the potential for polar effects, is
      essential to studies of both pathogenesis and basic bacterial physiology. Here we
      describe a three-phase approach for generating unmarked deletions in Legionella
      pneumophila by constructing a mutant allele in E. coli using lambda-Red
      recombination, so-called recombineering; transferring the allele onto the L.
      pneumophila chromosome by natural transformation; and then removing the
      selectable marker by utilizing the Flp site-specific recombinase. This strategy
      can decrease the amount of clone screening required while also increasing the
      percentage of the time the desired allele is obtained on the first attempt. The
      approach is particularly suited for constructing multiple unmarked deletions in a
      single strain in fewer steps than traditional methods.

PMID- 23150397
TI  - Natural biofilm formation with Legionella pneumophila.
AB  - Biofilm formation could be studied in various conditions. Most of the studies
      with Legionella pneumophila used monospecies biofilm in culture media. In some
      cases, it is important to study bacteria in conditions more close to
      environmental conditions. In this paper, we describe protocols to produce natural
      biofilms from river water that were spiked with L. pneumophila.

PMID- 23150398
TI  - Production of L. pneumophila monospecies biofilms in a low-nutrient-concentration
      medium.
AB  - In aquatic environments such as water distribution systems, Legionella
      pneumophila persistence is -correlated to the presence of a biofilm. The method
      described here permits the formation of a monospecies L. pneumophila biofilm in
      microplates, enabling the screening of multiple parameters. The culture medium
      used has a low nutrient concentration compared to the classical Buffered Yeast
      Extract culture medium. Hence, bacterial growth occurs in the sessile phase,
      allowing the formation of three-dimensional structures.

PMID- 23150399
TI  - Enrichment of outer membrane vesicles shed by Legionella pneumophila.
AB  - The production of outer membrane vesicles (OMVs) is a widespread phenomenon
      employed by bacteria to secrete cell envelope components into the environment. A
      contribution of Legionella pneumophila OMVs to the pathogenesis of Legionnaires'
      disease is likely due to the high number of virulence-related proteins in the
      vesicles. OMVs are isolated from the supernatant of liquid cultures of L.
      pneumophila. After low-speed centrifugation, residual bacteria and cell fragments
      are eliminated by passing the supernatant through a filter. OMVs are pelleted by
      ultracentrifugation and resuspended in buffer. The isolated OMVs can be analyzed
      for their molecular components and their interactions with host structures,
      bacterial cells, or surfaces.

PMID- 23150400
TI  - Analysis of legionella infection by flow cytometry.
AB  - Legionella pneumophila infects and replicates in environmental protozoa and
      metazoan macrophages within a specific vacuole. The infection of phagocytes by L.
      pneumophila can be assessed by an agar plating assay or by fluorescence
      microscopy. Here, we describe the analysis of Legionella infection by automated
      flow cytometry using wild-type and mutant bacteria that constitutively produce
      the green fluorescent protein (GFP). Advantages of the flow cytometry technique
      include (1) a software-assisted multiple parameter analysis of Legionella
      infections in real-time at distinct stages of the infection cycle, (2) the
      simultaneous and fast acquisition of a high number of data points, and (3) a
      characterization of the infecting bacteria in parallel with the infected host
      cells.

PMID- 23150401
TI  - Analysis of Legionella infection using RNAi in Drosophila cells.
AB  - RNA interference (RNAi) is the process of specific gene silencing by the use of
      double-stranded RNA (dsRNA). In cultured Drosophila cells, RNAi methodologies are
      well established and easily executed: dsRNA, when added to the cell culture
      medium, is efficiently internalized by the cells and, through the activity of
      endogenous processing machinery, targets the specified mRNA for degradation
      resulting in reduced levels of its encoded protein. This technique has proven
      very useful in studying the role of host genes during Legionella pneumophila
      infections, as it allows the effect of host factor depletion on intracellular
      growth of the bacterium to be examined. In this chapter we present the methods
      commonly used in our laboratory to study intracellular growth of L. pneumophila
      using dsRNA in Drosophila cells.

PMID- 23150402
TI  - Immunofluorescence imaging of legionella infection in vitro.
AB  - Upon uptake into a host cell, the intracellular bacterium Legionella pneumophila
      is not degraded on the lysosomal pathway but efficiently establishes a highly
      specialized replicative vacuole in which it readily multiplies. As many Icm/Dot
      type 4 secretion translocated bacterial effectors contribute to the establishment
      of this subcellular compartment in close interaction with host cell trafficking
      pathways, the analysis of the intracellular localization of this bacterium during
      infection is of pivotal importance to dissect the cellular and bacterial
      components of this process. In this chapter we describe a protocol for
      immunofluorescence microscopy in fixed mammalian and amoebal cells as well as
      transfection protocols to produce host cells expressing fluorescently labeled
      proteins as intracellular trafficking markers.

PMID- 23150403
TI  - Electron microscopy of legionella and legionella-infected cells.
AB  - Those investigators who study the morphology of Legionella and Legionella
      infected cells have greatly benefited from the superior resolution afforded by
      electron microscopy (EM). It can also be said with confidence that EM will
      continue to reveal as yet to be discovered features of this fascinating
      intracellular pathogen. In this chapter we detail our practical experience in the
      application of three transmission electron microscopy (TEM) techniques to the
      study of Legionella: conventional ultrastructural analysis, immuno-gold labeling,
      and negative staining. Each of these techniques has particular, well-defined
      applications, which are discussed in the context of our in-house developed
      methods. We invite researchers to try the methods given here in the study of
      Legionella, and adopt TEM as part of their research tools arsenal.

PMID- 23150404
TI  - Pathogen vacuole purification from legionella-infected amoeba and macrophages.
AB  - Legionella pneumophila replicates intracellularly in environmental and immune
      phagocytes within a unique membrane-bound compartment, the Legionella-containing
      vacuole (LCV). Formation of LCVs is strictly dependent on the Icm/Dot type IV
      secretion system and the translocation of "effector" proteins into the cell. Some
      effector proteins decorate the LCV membrane and subvert host cell vesicle
      trafficking pathways. Here we describe a method to purify intact LCVs from
      Dictyostelium discoideum amoebae and RAW 264.7 murine macrophages. The method
      comprises a two-step protocol: first, LCVs are enriched by immuno-magnetic
      separation using an antibody against a bacterial effector protein specifically
      localizing to the LCV membrane, and second, the LCVs are further purified by
      density gradient centrifugation. The purified LCVs can be characterized by
      proteomics and other biochemical approaches.

PMID- 23150405
TI  - Methods for determining protein translocation by the Legionella pneumophila
      Dot/Icm type IV secretion system.
AB  - Legionella pneumophila the causative agent of Legionnaires' disease, actively
      manipulates host cell -processes to establish a membrane-bound replication
      vacuole permissive for its replication. Establishment of such replication niche
      requires the Dot/Icm type IV secretion system which translocates a plethora of
      effectors into host cells. Determining whether a particular protein is a
      substrate of the transporter is a prerequisite for subsequent functional studies.
      Thus, a variety of methods have been developed in the last decade to measure
      Dot/Icm-dependent delivery of protein into the host cell. The combination of
      these methods and the appropriate screening strategies has allowed for the
      identification of more than 270 translocated proteins. These efforts have laid a
      solid foundation for further study of the roles of these proteins in the
      interactions between L. pneumophila and its host. Here, we summarized the
      experimental details of these methods.

PMID- 23150406
TI  - Subcellular localization of legionella Dot/Icm effectors.
AB  - The translocation of effector proteins by the Dot/Icm type IV secretion system is
      central to the ability of Legionella pneumophila to persist and replicate within
      eukaryotic cells. The subcellular localization of translocated Dot/Icm proteins
      in host cells provides insight into their function. Through co-staining with host
      cell markers, effector proteins may be localized to specific subcellular
      compartments and membranes, which frequently reflects their host cell target and
      mechanism of action. In this chapter, we describe protocols to (1) localize
      effector proteins within cells by ectopic expression using green fluorescent
      protein fusions and (2) localize effector proteins within infected cells using
      epitope-tagged effector proteins and immuno-fluorescence microscopy.

PMID- 23150407
TI  - Purification and characterization of legionella U-box-type E3 ubiquitin ligase.
AB  - Bacterial virulence proteins often mimic host eukaryotic proteins to modify or
      disturb host cellular -pathways. Increasing lines of evidence show that many
      bacterial effector proteins have E3 ubiquitin ligase activity. The effector
      protein LubX is one such bacterial E3 ubiquitin ligase. We describe here the
      method to purify soluble LubX protein using GST-tag and Escherichia coli
      overexpression systems. Using the purified protein together with recombinant
      ubiquitin, E1, and E2 enzymes, ubiquitin ligase activity is analyzed by the in
      vitro ubiquitination assay.

PMID- 23150408
TI  - Legionella phospholipases implicated in infection: determination of enzymatic
      activities.
AB  - The intracellularly replicating lung pathogen Legionella pneumophila expresses a
      multitude of different phospholipases which are important virulence tools during
      host cell infection. To study the lipolytic properties including substrate
      specificities of potential L. pneumophila phospholipases A (PLA), we used
      different assays to monitor lipid hydrolysis. Here we describe methods for
      quantitative analysis of liberated fatty acids via a photometric assay and for
      identification of specific lipids which are generated by PLA action by means of
      lipid extraction and thin-layer chromatography. The latter approach also
      identifies glycerophospholipid:cholesterol acyltransferase activity which may be
      associated with PLA activity and is responsible for the transfer of fatty acids
      derived from a phospholipid to an acceptor molecule, such as cholesterol. These
      methods applied for specific L. pneumophila enzyme knockout mutants compared to
      the wild type or for recombinantly expressed protein allow to conclude on
      substrate specificity and/or contribution of a specific enzyme to the total
      lipolytic activity. Further, via analysis of separated cellular fractions, such
      as culture supernatants and cell lysates, information on the localization of the
      enzymes will be obtained.

PMID- 23150409
TI  - Interactions of legionella effector proteins with host phosphoinositide lipids.
AB  - By means of the Icm/Dot type IV secretion system Legionella pneumophila
      translocates several effector proteins into host cells, where they anchor to the
      cytoplasmic face of the LCV membrane by binding to phosphoinositide (PI) lipids.
      Thus, phosphatidylinositol-4-phosphate anchors the effector proteins SidC and
      SidM, which promote the interaction of LCVs with the ER and the secretory vesicle
      trafficking -pathway. In this chapter, we describe protocols to (1) identify PI
      binding proteins in Legionella lysates using PI-beads, (2) determine PI-binding
      specificities and affinities of recombinant Legionella effector proteins by
      protein-lipid overlays, and (3) use Legionella effectors to identify cellular PI
      lipids.

PMID- 23150410
TI  - Characterization of legionella lipopolysaccharide.
AB  - The lipopolysaccharide(LPS) of Legionella spp. is an immuno-dominant antigen and
      the basis for Legionella pneumophila serogroup classification. The LPS shows a
      peculiar structure composed of a very hydrophobic lipid A acylated by long chain
      fatty acids and an O-antigen-specific chain consisting of homopolymeric
      legionaminic acid. In this chapter we describe a method for the isolation of LPS
      from L. pneumophila. In the first part we describe the chemical purification, in
      the second part we outline the application of monoclonal antibody (mAb) in
      Western blot and immuno-localization by indirect immunofluorescence. This report
      does not describe physico-chemical methods that analyze the structure of
      lipopolysaccharide entities.

PMID- 23150411
TI  - The tetrahymena and acanthamoeba model systems.
AB  - Although the study of protozoology has been active for centuries, very few
      current academic curricula incorporate requirements or even options for
      coursework on the study of protists; yet, protozoa are becoming widely recognized
      by investigators as organisms that play a significant role in the evolution,
      pathogenicity, protection and amplification of human pathogens in the
      environment. This is particularly true for the study of Legionella, as this
      accidental human pathogen has naturally evolved to infect protozoa in fresh water
      environments. Researchers have made great progress in the study of pathogenicity,
      evolution, and ecology of Legionella and its protozoan hosts, which include
      amoebae and ciliated protozoa. Our own collaboration in this field has been
      active for over a decade, and we have gained a valuable experience working with
      these protozoa, particularly aspects of their biology and the methods needed to
      address new experimental concepts. Therefore, in this chapter we provide the most
      effective procedures that we have developed or modified through our years of
      practice. We also offer notes on what procedures, in our opinion, should be
      avoided; and we provide the rationale for such precautions.

PMID- 23150412
TI  - Dictyostelium host response to legionella infection: strategies and assays.
AB  - The professional phagocyte Dictyostelium discoideum is a simple eukaryotic
      microorganism, whose natural habitat is deciduous forest soil and decaying
      leaves, where the amoebae feed on bacteria and grow as separate, independent,
      single cells. In the last decade, the organism has been successfully used as a
      host for several human pathogens, including Legionella pneumophila, Mycobacterium
      avium and Mycobacterium marinum,Pseudomonas aeruginosa, Klebsiella pneumoniae,
      Cryptococcus neoformans, and Salmonella typhimurium. To dissect the complex cross
      talk between host and pathogen Dictyostelium offers easy cultivation, a high
      quality genome sequence and excellent molecular genetic and biochemical tools.
      Dictyostelium cells are also extremely suitable for cell biological studies,
      which in combination with in vivo expression of fluorescence-tagged proteins
      allow investigating the dynamics of bacterial uptake and infection. Inactivation
      of genes by homologous recombination as well as gene rescue and overexpression
      are well established and a large mutant collection is available at the
      Dictyostelium stock center, favoring identification of host resistance or
      susceptibility genes. Here, we briefly introduce the organism, address the value
      of Dictyostelium as model host, describe strategies to identify host cell factors
      important for infection followed by protocols for cell culture and storage,
      uptake and infection, and confocal microscopy of infected cells.

PMID- 23150413
TI  - The Caenorhabditis elegans model of Legionella infection.
AB  - Caenorhabditis elegans can serve as a simple genetic host to study interactions
      between Legionellaceae and their hosts, and to examine the contribution of
      specific gene products to virulence and immunity. C. elegans nematodes have
      several appealing attributes as a host organism; they are inexpensive, have
      robust genetic analysis tools, have a simple anatomy yet display a wide range of
      complex behaviors, and, as invertebrates, do not require animal ethics protocols.
      Use of C. elegans as a host model complements cell-based models, providing
      additional support and consistency of the experimental data obtained from
      multiple models. The C. elegans innate immune system functions similarly to that
      of the alveolar macrophage including the apoptosis [e.g. programmed cell death
      (PCD)] pathway located within the germline. The digestive tract of C. elegans is
      a primary interface between the innate immune system and bacterial pathogens.
      Thus, the C. elegans host model provides an alternative approach to investigate
      Legionella pneumophila immunopathogenesis.

PMID- 23150414
TI  - Infection of nonphagocytic host cells by legionella.
AB  - Legionella pneumophila is an intracellular pathogen of free-living protozoa that
      can also infect alveolar macrophages, L929 fibroblast cells, and HeLa cells.
      Infection of nonphagocytic cells by L. pneumophila can be used to study invasion
      mechanisms, compare infectivity of different strains and identify factors
      important for virulence. Virulent strains of L. pneumophila exposed to monolayers
      of L929 cells are able to invade and form virus-like plaques, which can be
      enumerated as a measure of infectivity. Invasiveness of HeLa cells can also be
      used to evaluate relative infectivity and to study mechanisms of invasion and to
      track the development of cyst-like forms. The detailed methods of both the L929
      plaque assay and HeLa cell invasion assay are described.

PMID- 23150415
TI  - Analyzing caspase-1 activation during Legionella pneumophila infection in
      macrophages.
AB  - Caspase-1 is a critical factor in the innate immune response to Legionella
      pneumophila. The development of methods for analyzing caspase-1 activation
      pathways and downstream caspase-1-associated activities has helped in
      understanding the regulation of this protease and the signaling components
      involved. Here we outline methods for directly detecting active caspase-1,
      measuring caspase-1 activities and analyzing components involved in the
      regulation of caspase-1 during L. pneumophila infection in macrophages.

PMID- 23150416
TI  - The mouse as a model for pulmonary legionella infection.
AB  - Legionella pneumophila is an intracellular bacterium that was evolutionarily
      selected to survive in freshwater environments by infecting free-living
      unicellular protozoa. Once humans inhale contaminated water droplets, the
      bacteria reach the pulmonary alveoli where they are phagocytized by resident
      alveolar macrophages. Depending on host immunity and bacterial virulence genes,
      the infection may progress to an acute pneumonia called Legionnaires' disease,
      which can be fatal. Of note, an effective immune response is critical to the
      outcome of the human infection. These clinical observations highlight the
      importance of animal models of pulmonary infection for in vivo investigation of
      bacterial pathogenesis and host responses. In this chapter we provide detailed
      protocols for intranasal infection of mouse with L. pneumophila.

PMID- 23150417
TI  - Assessment of legionella-specific immunity in mice.
AB  - Legionella pneumophila is the causative agent of the potentially fatal
      Legionnaires' disease in humans. Mice have proved to be valuable model organisms
      to study the pathogenesis of this intracellular bacterium, as well as immune
      responses against it. In this chapter we describe a selection of mouse infection
      protocols to study the innate and adaptive immune responses raised after an
      infection with Legionella. Included are protocols for systemic and pulmonary
      infections, surgical collection of organs as well as determination of cell
      composition, cytokines, and antibody titers therein. Furthermore, we describe an
      immunohistology protocol to analyze lung tissue sections by fluorescence
      microscopy.

PMID- 23150418
TI  - The Guinea pig model of legionnaires' disease.
AB  - The guinea pig pneumonia model mimics Legionnaires' disease as seen in
      immunocompromised humans, with high untreated fatality rates and as such lends
      itself to studies of experimental chemotherapy. Guinea pig infection is also used
      to assess relative virulence of different Legionella bacterial strains, and has
      also been used to study host immune defenses. Here I describe the method used to
      produce Legionella sp. pneumonia in the guinea pig using the intratracheal
      infection technique. This method uses directly observed intratracheal injection
      of a bacterial suspension, requiring surgical exposure of the trachea.

PMID- 23150419
TI  - Human susceptibility to legionnaires' disease.
AB  - Legionella pneumophila is a facultative intracellular pathogen that is an
      important cause of pneumonia. Although host factors that may predispose to
      acquisition of Legionnaire's Disease (LD) include comorbid illnesses (e.g.,
      diabetes, chronic lung disease), age, male sex, and smoking, many individuals
      have no identifiable risk factors. Some studies suggest that genetic factors may
      enhance susceptibility to LD. In this chapter we discuss current techniques and
      scientific methods to identify genetic susceptibility factors. These genetic
      studies provide insight into the human immune response to intracellular pathogens
      and may improve strategies for treatment and vaccine development.

PMID- 23150420
TI  - cDNA library construction for next-generation sequencing to determine the
      transcriptional landscape of Legionella pneumophila.
AB  - The adaptation of Legionella pneumophila to the different conditions it
      encounters in the environment and in the host is governed by a complex regulatory
      system. Current knowledge of these regulatory networks and the transcriptome
      responses of L. pneumophila is mainly based on microarray analysis and limited to
      transcriptional products of annotated protein-coding genes. The application of
      the Next-Generation Sequencing (NGS) technology allows now genome-wide strand
      specific sequencing and accurate determination of all expressed regions of the
      genome to reveal the complete transcriptional network and the dynamic interplay
      of specific regulators on a genome-wide level. NGS-based techniques promote
      deeper understanding of the global transcriptional organization of L. pneumophila
      by identifying transcription start sites (TSS), alternative TSS and operon
      organization, noncoding RNAs, antisense RNAs, and 5'-/3'-untranslated regions. In
      this chapter we describe the construction of cDNA libraries for (1) RNA deep
      sequencing (RNA-seq) and (2) TSS mapping using the Illumina technology.

PMID- 23150421
TI  - Methods to study legionella transcriptome in vitro and in vivo.
AB  - The study of transcriptome responses can provide insight into the regulatory
      pathways and genetic factors that contribute to a specific phenotype. For
      bacterial pathogens, it can identify putative new virulence systems and shed
      light on the mechanisms underlying the regulation of virulence factors.
      Microarrays have been previously used to study gene regulation in Legionella
      pneumophila. In the past few years a sharp reduction of the costs associated with
      microarray experiments together with the availability of relatively inexpensive
      custom-designed commercial microarrays has made microarray technology an
      accessible tool for the majority of researchers. Here we describe the
      methodologies to conduct microarray experiments from in vitro and in vivo
      samples.

PMID- 23150422
TI  - Co-immunoprecipitation: protein-RNA and protein-DNA interaction.
AB  - Transcriptional and posttranscriptional regulators play a critical role in
      allowing a bacterium to adapt to the diverse environments and conditions it
      encounters. In order to characterize the role of these regulators the
      identification of their specific interaction partners is of utmost importance. Co
      immunoprecipitation (IP) is based on antigen/antibody complex formation to purify
      a protein of interest from the rest of the samples together with its interaction
      partner. This method allows us to study direct interaction of a regulator with
      its specific binding partners like protein-RNA, protein-DNA, or protein-protein
      interactions. IP typically requires careful optimization and troubleshooting
      depending on the varying physicochemical characteristics of the protein of
      interest. In this chapter we present a starting point and the basic guidelines to
      obtain the best possible results from an IP experiment with subsequent use of new
      generation sequencing techniques to detect mRNA or ncRNA targets (RIPseq) and
      protein-DNA interactions (ChIPseq).

PMID- 23150423
TI  - Identification of legionella effectors using bioinformatic approaches.
AB  - Legionella pneumophila the causative agent of Legionnaires' disease, actively
      manipulates host cell processes to establish a replication niche inside host
      cells. The establishment of its replication niche requires a functional Icm/Dot
      type IV secretion system which translocates about 300 effector proteins into host
      cells during infection. Many of these effectors were first identified as effector
      candidates by several bioinformatic approaches, and these predicted effectors
      were later examined experimentally for translocation and a large number of which
      were validated as effector proteins. Here, I summarized the bioinformatic
      approaches that were used to identify these effectors.

PMID- 23150425
TI  - The management of wound-related procedural pain (volitional incident pain) in
      advanced illness.
AB  - PURPOSE OF REVIEW: The prevention and treatment of wound-related procedural pain
      is one of the greatest areas of unmet need within wound management. Also referred
      to as 'Volitional Incident Pain', it is the most prevalent subtype of
      breakthrough pain experienced by patients afflicted with wounds. Novel
      formulations of existing analgesics are now available to address this challenge.
      RECENT FINDINGS: This review focuses on the principles of breakthrough pain
      assessment including those patients with cognitive impairment. Current management
      principles are discussed with an emphasis on the novel formulations of fentanyl
      citrate that may be delivered through the sublingual, buccal, and nasal mucosal
      routes. SUMMARY: Novel formulations of fentanyl citrate, delivered through an
      array of noninvasive routes, allow for rapid-onset and short-acting effects that
      better match the onset and duration of wound-related procedural pain.

PMID- 23150426
TI  - Change of boron substitution improves the lasing performance of Bodipy dyes: a
      mechanistic rationalisation.
AB  - Bodipy laser dyes are highly efficient but degrade rapidly in solution by
      reacting with in situ generated singlet oxygen ((1)O(2)). To increase the lasing
      lifetimes of these dyes, we have designed and synthesised two different congeners
      of the widely studied Pyrromethene 567 (PM567) by substitution at the boron
      centre and/or at both the boron centre and the meso position. The two new dyes
      showed high lasing efficiencies with increased photostability. The results of
      theoretical and pulse radiolysis studies revealed that the substitution at the
      boron centre reduced the (1)O(2) generation capacity of these dyes as well as
      their rate of reaction with (1)O(2), thereby enhancing their lifetimes even under
      lasing conditions.

PMID- 23150424
TI  - An investigation of risk factors for renal cell carcinoma by histologic subtype
      in two case-control studies.
AB  - To investigate whether renal cell carcinoma (RCC) histologic subtypes possess
      different etiologies, we conducted analyses of established RCC risk factors by
      subtype (clear cell, papillary and chromophobe) in two case-control studies
      conducted in the United States (1,217 cases, 1,235 controls) and Europe (1,097
      cases, 1,476 controls). Histology was ascertained for 706 U.S. cases (58% of
      total) and 917 European cases (84%) through a central slide review conducted by a
      single pathologist. For the remaining cases, histology was abstracted from the
      original diagnostic pathology report. Case-only analyses were performed to
      compute odds ratios (ORs) and 95% confidence intervals (CI) summarizing subtype
      differences by age, sex and race. Case-control analyses were performed to compute
      subtype-specific ORs for other risk factors using polytomous regression. In case
      only analyses, papillary cases (N = 237) were older (OR = 1.2, 95% CI = 1.1-1.4
      per 10-year increase), less likely to be female (OR = 0.5, 95% CI = 0.4-0.8) and
      more likely to be black (OR = 2.6, 95% CI = 1.8-3.9) as compared to clear cell
      cases (N = 1,524). In case-control analyses, BMI was associated with clear cell
      (OR = 1.2, 95% CI = 1.1-1.3 per 5 kg/m(2) increase) and chromophobe RCC (N = 80;
      OR = 1.2, 95% CI = 1.1-1.4), but not papillary RCC (OR = 1.1, 95% CI = 1.0-1.2;
      test versus clear cell, p = 0.006). No subtype differences were observed for
      associations with smoking, hypertension or family history of kidney cancer. Our
      findings support the existence of distinct age, sex and racial distributions for
      RCC subtypes, and suggest that the obesity-RCC association differs by histology.

PMID- 23150427
TI  - In vitro cytochrome p450 activity decreases in children with high pediatric end
      stage liver disease scores.
AB  - To improve the modeling and simulation of pharmacokinetics in pediatric patients,
      research into developmental and disease-specific determinants is needed. This
      article describes the evaluation of the activity of in vitro cytochrome P450
      (P450), an important enzyme family in drug metabolism, in children with hepatic
      dysfunction. The activity of six P450 isoforms (CYP1A2, 2C9, 2C19, 2D6, 2E1, and
      3A4) was evaluated in 31 patients with different pathologies, predominantly
      biliary atresia (n = 23). Hypervariable activity was observed for all the
      isoforms. Compared with average adult activity, low activity levels were seen for
      CYP1A2, 2C19, 2E1, and 3A4. For CYP2E1 and 3A4, a positive correlation between
      activity and abundance was observed. Age, comedication, and genotype could not be
      used as predictors for P450 activity in this patient population. In contrast, the
      pediatric end-stage liver disease score was negatively correlated with the
      ln(activity). This finding suggests a decrease in P450 activity with
      deteriorating hepatic function. Moreover, the activity of all isoforms was
      correlated, demonstrating a concomitant decrease of all isoforms in young
      patients with liver disease. To our knowledge, this is the first study to
      evaluate P450 activity in children with hepatic impairment. The presented data
      may provide support in the further optimization of a disease-specific model in
      this patient population.

PMID- 23150429
TI  - Gamma-amino butyric acid and the A-type receptor suppress decidualization of
      mouse uterine stromal cells by down-regulating cyclin D3.
AB  - Uterine decidualization, characterized by stromal cell proliferation and
      differentiation into polyploid decidual cells, is critical to the establishment
      of pregnancy in mice, although the mechanism underlying this process remains
      poorly understood. This study is the first to investigate the expression of gamma
      amino butyric acid (GABA) and the GABA A-type receptor pi subunit (GABPR) in the
      early-pregnancy mouse uterus and their roles in decidualization. The expression
      of GABRP was detected from Day 4 to 8 of pregnancy. The effects of GABA and GABA
      A-type receptor on cell proliferation and apoptosis were investigated using the
      Cell Titer 96(r) AQueous One Solution Cell Proliferation Assay and flow
      cytometry. The levels of cyclin D3 protein were measured in cultured stromal
      cells artificially induced to undergo decidualization, and treated with GABA and
      a GABA A-type receptor agonist or antagonist, respectively, at the same time.
      mRNA expression of gabrp in implantation sites was lower than that in inter
      implanted sites. GABA and GABRP protein were localized in the luminal and
      glandular epithelium, stromal cells, and decidual cells. In vitro, GABPR protein
      level was decreased in cultured stromal cells during the decidualization process.
      The addition of GABA and the GABA A-type receptor agonist Muscimol inhibited
      stromal cell proliferation, promoted apoptosis, and arrested cells in S-phase,
      followed by decreased expression of cyclin D3. These results show that in mice,
      GABA was actively involved in inhibiting stromal cell proliferation and
      suppresses decidualization progress through GABA A-type receptors by down
      regulating cyclin D3 level.

PMID- 23150428
TI  - Hepatic Cyp2d and Cyp26a1 mRNAs and activities are increased during mouse
      pregnancy.
AB  - There is considerable evidence that drug disposition is altered during human
      pregnancy and based on probe drug studies, CYP2D6 activity increases during human
      pregnancy. The aim of this study was to determine whether the changes of CYP2D6
      activity observed during human pregnancy could be replicated in the mouse, and
      explore possible mechanisms of increased CYP2D6 activity during pregnancy.
      Cyp2d11, Cyp2d22, Cyp2d26 and Cyp2d40 mRNA was increased (P < 0.05) on
      gestational days (GD) 15 and 19 compared with the non-pregnant controls. There
      was no change (P > 0.05) in Cyp2d9 and Cyp2d10 mRNA. In agreement with the
      increased Cyp2d mRNA, Cyp2d-mediated dextrorphan formation from dextromethorphan
      was increased 2.7-fold (P < 0.05) on GD19 (56.8+/-39.4 pmol/min/mg protein) when
      compared with the non-pregnant controls (20.8+/-11.2 pmol/min/mg protein). An
      increase in Cyp26a1 mRNA (10-fold) and retinoic acid receptor (Rar)beta mRNA (2.8
      fold) was also observed during pregnancy. The increase in Cyp26a1 and Rarbeta
      mRNA during pregnancy indicates increased retinoic acid signaling in the liver
      during pregnancy. A putative retinoic acid response element was identified within
      the Cyp2d40 promoter and the mRNA of Cyp2d40 correlated (P < 0.05) with Cyp26a1
      and Rarbeta. These results show that Cyp2d mRNA is increased during mouse
      pregnancy the and mouse may provide a suitable model to investigate the
      mechanisms underlying the increased clearance of CYP2D6 probes observed during
      human pregnancy. Our findings also suggest that retinoic acid signaling in the
      liver is increased during pregnancy, which may have broader implications to
      energy homeostasis in the liver during pregnancy.

PMID- 23150430
TI  - Tailoring encodable lanthanide-binding tags as MRI contrast agents.
AB  - Lanthanide-binding tags (LBTs), peptide-based coexpression tags with high
      affinity for lanthanide ions, have previously been applied as luminescent probes
      to provide phasing for structure determination in X-ray crystallography and to
      provide restraints for structural refinement and distance information in NMR. The
      native affinity of LBTs for Gd(3+)  indicates their potential as the basis for
      engineering of peptide-based MRI agents. However, the lanthanide coordination
      state that enhances luminescence and affords tightest binding would not be ideal
      for applications of LBTs as contrast agents, due to the exclusion of water from
      the inner coordination sphere. Herein, we use structurally defined LBTs as the
      starting point for re-engineering the first coordination shell of the lanthanide
      ion to provide for high contrast through direct coordination of water to Gd(3+) 
      (resulting in the single LBT peptide, m-sLBT). The effectiveness of LBTs as MRI
      contrast agents was examined in vitro through measurement of binding affinity and
      proton relaxivity. For imaging applications that require targeted observation,
      fusion to specific protein partners is desirable. However, a fusion protein
      comprising a concatenated double LBT (dLBT) as an N-terminal tag for the model
      protein ubiquitin had reduced relaxivity compared with the free dLBT peptide.
      This limitation was overcome by the use of a construct based on the m-sLBT
      sequence (q-dLBT-ubiquitin). The structural basis for the enhanced contrast was
      examined by comparison of the X-ray crystal structure of xq-dLBT-ubiquitin
      (wherein two tryptophan residues are replaced with serine), to that of dLBT
      ubiquitin. The structure shows that the backbone conformational dynamics of the
      MRI variant may allow enhanced water exchange. This engineered LBT represents a
      first step in expanding the current base of specificity-targeted agents
      available.

PMID- 23150431
TI  - CREB-mediated Bcl-2 expression contributes to RCAN1 protection from hydrogen
      peroxide-induced neuronal death.
AB  - Regulator of calcineurin 1 (RCAN1) is located on the Down syndrome critical
      region (DSCR) locus in human chromosome 21. In this study, we investigated the
      functional role of RCAN1 in the reactive oxygen species (ROS)-mediated neuronal
      death signaling. We found that RCAN1 was able to protect the cells from H(2)O(2) 
      induced cytotoxicity. The expression of RCAN1 caused an inhibition of the
      H(2)O(2) -induced activation of mitogen-activated protein kinases (MAPKs) and AP
      1. In contrast, RCAN1 significantly enhanced the activity of cAMP response
      element-binding protein (CREB). Furthermore, RCAN1 induced the expression of the
      CREB target gene, Bcl-2. Consistently, knockdown of endogenous RCAN1 using shRNA
      down regulated the phosphorylation of CREB and the expression of Bcl-2, which
      protects the cells from H(2)O(2) -induced cytotoxicity. Our data provide a new
      mechanism for the cytoprotective function of RCAN1 in response to oxidant-induced
      apoptosis.

PMID- 23150433
TI  - Detecting and quantifying p53 isoforms at mRNA level in cell lines and tissues.
AB  - The TP53 gene expresses at least nine different mRNA variants (p53 isoform
      mRNAs), including the one encoding the canonical p53 tumor suppressor protein. We
      have developed scientific tools to specifically detect and quantify p53 isoform
      expression at mRNA level by nested RT-PCR (reverse transcription-polymerase chain
      reaction) and quantitative real-time RT-PCR (RT-qPCR using the TaqMan((r))
      chemistry). Here, we describe these two methods, while highlighting essential
      points with regard to the analysis of p53 isoform mRNA expression.

PMID- 23150432
TI  - Cell-based selection provides novel molecular probes for cancer stem cells.
AB  - Cancer stem cells (CSC) represent a malignant subpopulation of cells in
      hierarchically organized tumors. They constitute a subpopulation of malignant
      cells within a tumor mass and possess the ability to self-renew giving rise to
      heterogeneous tumor cell populations with a complex set of differentiated tumor
      cells. CSC may be the cause of metastasis and therapeutic refractory disease.
      Because few markers exist to identify and isolate pure CSC, we used cell-based
      Systematic Evolution of Ligands by EXponential enrichment (cell-SELEX) to create
      DNA aptamers that can identify novel molecular targets on the surfaces of live
      CSC. Out of 22 putative DNA sequences, 3 bound to ~90% and 5 bound to ~15% of
      DU145 prostate cancer cells. The 15% of cells that were positive for the second
      panel of aptamers expressed high levels of E-cadherin and CD44, had high aldehyde
      dehydrogenase 1 activity, grew as spheroids under nonadherent culture conditions,
      and initiated tumors in immune-compromised mice. The discovery of the molecular
      targets of these aptamers could reveal novel CSC biomarkers.

PMID- 23150434
TI  - Detecting p53 isoforms at protein level.
AB  - The human p53 protein isoforms are expressed in several cell lines and modulate
      p53 tumor suppressor -activity, mainly through modulation of gene expression (1
      4). Thus, identifying the pattern of p53 isoforms expression in cell lines is a
      key step for future studies of the p53 network (5). At the moment, the detection
      of p53 protein isoforms is based on the use of a panel of antibodies allowing
      their identification by comparing their molecular weights and their detection
      pattern by different antibodies (6). Here, classical protocols supplemented with
      technical know-how are described to detect p53 protein isoforms at protein level
      by Western blotting and immunoprecipitation. Furthermore, a simple method to
      study the impact of p53 protein isoforms on p53 transcriptional activity through
      luciferase reporter gene assays is provided.

PMID- 23150435
TI  - Autophagy, senescence, and apoptosis.
AB  - This chapter presents methods for interrogating the involvement of p53 in
      signaling to apoptosis, autophagy, and senescence. The well-known association of
      p53 with the stress response to chemotherapy and radiation is the basis for
      presenting these approaches. The development of quantitative and efficient in
      vitro assays has enabled researchers to overcome the limitations of previous
      methodologies. This chapter provides up-to-date procedures relating to the
      molecular networks in which the p53 protein has been shown to play a central role
      that allows damaged cells either to adapt to stress (autophagy and/or senescence)
      or to progress towards programmed cell death (apoptosis).

PMID- 23150436
TI  - p53 and cell cycle effects after DNA damage.
AB  - Flow cytometry, a valuable technique that employs the principles of light
      scattering, light excitation, and emission of fluorochrome molecules, can be used
      to assess the cell cycle position of individual cells based on DNA content. After
      the permeabilization of cells, the DNA can be stained with a fluorescent dye.
      Cells which have a 2N amount of DNA can be distinguished from cells with a 4N
      amount of DNA, making flow cytometry a very useful tool for the analysis of cell
      cycle checkpoints following DNA damage. A critical feature of the cellular
      response to DNA damage is the ability to pause and repair the damage so that
      consequential mutations are not passed along to daughter generations of cells. If
      cells arrest prior to DNA replication, they will contain a 2N amount of DNA,
      whereas arrest after replication but before mitosis will result in a 4N amount of
      DNA. Using this technique, the role that p53 plays in cell cycle checkpoints 
      following DNA damage can be evaluated based on changes in the profile of the G1,
      S, and G2/M phases of the cell cycle.

PMID- 23150437
TI  - p53 Ubiquitination and proteasomal degradation.
AB  - p53 levels and activity are controlled in large part through regulated
      ubiquitination and subsequent destruction by the 26S proteasome.
      Monoubiquitination of p53 is mediated primarily by the RING-finger E3 ubiquitin
      ligase MDM2 and impacts p53 activity through modulation of p53 localization and
      transcription activities. Recently, several E4 ubiquitin ligases (E4s) have been
      identified which serve to extend these monoubiquitin chains. The ubiquitin ligase
      activity of these factors toward p53, and their contribution to p53 degradation,
      can be studied using a variety of in vitro and in vivo methods and reagents which
      will be described in this chapter. These methods include in vivo ubiquitination
      of p53 using HA-ubiquitin or his-ubiquitin; the in vitro E3 ubiquitin ligase
      assay, in which ubiquitin reaction components (URC) are incubated with a purified
      E3 or E4 ligase; a one-step E4 assay, in which URC are incubated with a
      substrate, E3, and E4; and a two-step E4 assay in which p53 is monoubiquitinated
      in an E3 reaction, and subsequently purified and incubated with an E4. Finally,
      we will describe an in vitro degradation assay in which ubiquitinated p53 is
      incubated with purified 26S proteasomes. Together, these assays can be used to
      provide insight into the biochemical nature of p53 ubiquitination and
      degradation.

PMID- 23150438
TI  - Identification of p53 in mitochondria.
AB  - p53 is a master regulator of cell death pathways and has transcription-dependent
      and transcription-independent modes of action. Mitochondria are major signal
      transducers in apoptosis and are critical for p53-dependent cell death. Our lab
      and others have discovered that a fraction of stress-induced wild-type p53
      protein rapidly translocates to mitochondria upon various stress stimuli and
      exerts p53-dependent apoptosis. Suborganellar localization by various methods
      shows that p53 localizes to the surface of mitochondria. Direct targeting of p53
      to mitochondria is sufficient to induce apoptosis in p53-null cells, without
      requiring further DNA damage. Recently, p53 has been also shown to localize to
      other mitochondrial compartments such as the mitochondrial matrix where it plays
      a role in maintaining mitochondrial genome integrity. Here, we describe
      subcellular fractionation as a classic technique for detecting mitochondrial p53
      in cell extracts. It consists of cell homogenization by hypo-osmotic swelling,
      removal of nuclear components by low-speed centrifugation, and mitochondrial
      isolation by a discontinuous sucrose density gradient. Additionally, we describe
      a method for submitochondrial fractionation, performed by phosphate buffer
      mediated swelling/shrinking. p53 and other mitochondrial proteins can then be
      detected by standard immunoblotting procedures. The quality of mitochondrial
      isolates/subfractions can be verified for purity and intactness.

PMID- 23150439
TI  - Identification of novel mutant p53 interacting proteins by proteomic analysis.
AB  - Protein-protein interaction studies can provide valuable insight into protein
      function. One of the most practical and high-yielding approaches is
      immunoprecipitation of a bait protein followed by mass spectrometry to identify
      co-precipitating proteins. Here we describe an effective and simplified version
      of this method that can be performed in most laboratories using standard
      laboratory equipment (apart from the mass spectrometer). We further demonstrate
      the utility of this method to identify proteins that specifically interact with
      mutant forms of the tumor suppressor protein, p53.

PMID- 23150440
TI  - Identification of small molecules affecting p53-MDM2/MDMX interaction by
      fluorescence polarization.
AB  - Fluorescence polarization (FP) has become a powerful technique to quantitatively
      analyze the binding of a small soluble fluorescence-labeled probe to a larger
      soluble protein and its displacement by other molecules. Here, we describe a
      detailed protocol to identify small molecules capable of targeting p53-MDM2/MDMX
      interactions using a fluorescence polarization assay with Rhodamine-labeled p53
      peptides.

PMID- 23150441
TI  - Determine the effect of p53 on chemosensitivity.
AB  - The p53 tumor suppressor protein plays a central role in mediating the cellular
      response to a variety of stresses. Activation of p53 signaling will trigger cell
      cycle arrest or apoptosis in normal cells, depending on such factors as cell type
      and genetic context. The ability of a cell to circumvent either of these p53
      directed outcomes leads to inappropriate proliferation, thereby contributing to
      the development of cancer. As such, tumors frequently escape the apoptotic
      pathway in response to cell stress. DNA-damaging agents, however, achieve
      significant tumor cytotoxicity in spite of this hallmark characteristic. Tumors
      treated with DNA-damaging drugs often undergo alternate forms of cell death, such
      as senescence or mitotic catastrophe, in addition to apoptosis that may
      ultimately lead to regression. Although not a predictor of chemotherapy response
      in patients per se, p53 status in tumor-derived cells is frequently a determinant
      of the death pathway promoted by these agents. The cytotoxic effects of DNA
      damaging agents can be readily appreciated using such tools as cell cycle
      analysis, phopsho-H3(Ser10) immunoblotting, and annexin V detection.

PMID- 23150442
TI  - Measurement of chemosensitivity and growth rate in p53 expressing cells.
AB  - Chemoresistance and increased growth rate are two gain-of-function functions that
      mutant p53 is thought to possess. Here, we describe two methods for measuring the
      sensitiveness of cells to chemotherapeutic drugs and the rate of cell growth.
      Both of which can be used with a wide range of cell types. The clonogenic assay
      can be used with many different chemotoxic drugs and the growth assay described
      here presents an alternative to the MTT assay and allows for a long-term
      measurement of cell growth. These protocols are both easy, flexible, require
      relatively little effort, and are inexpensive to carry out.

PMID- 23150443
TI  - Mutant p53 in cell adhesion and motility.
AB  - Pro-oncogenic properties of mutant p53 were investigated with the aid of
      migration assays, adhesion assays, and soft agar growth assays using cells stably
      expressing gain-of-function p53 mutants. To determine cell migration, "wound
      healing" (scratch) assays and haptotactic (chamber) assays were used. H1299 cells
      expressing mutant p53 were found to migrate more rapidly than cells transfected
      with empty vector alone. Results from both types of migration assay were broadly
      similar. Migratory ability differed for different p53 mutants, suggesting allele
      specific effects. Cells expressing p53 mutants also showed enhanced adhesion to
      extracellular matrix compare to controls. Furthermore, stable transfection of
      mutant p53-H179L into NIH3T3 fibroblasts was sufficient to allow anchorage
      independent growth in soft agar.

PMID- 23150444
TI  - Use of the DNA fiber spreading technique to detect the effects of mutant p53 on
      DNA replication.
AB  - DNA replication involves a coordinated progression through S phase, and
      disruption of these regulated steps may cause gene abnormalities, which may lead
      to cancer. Different stages of DNA replication can be detected
      immunofluorescently that would indicate how replication is progressing in a cell
      population or under specific conditions. We describe a method for labeling
      replicating DNA with two nucleotide analogs, and then detecting the sequential
      patterns of incorporation using fluorescently labeled antibodies on DNA spread
      onto a glass slide. Quantification of the different types of replication patterns
      produced by this method reveals how replication is achieved under different
      conditions by the predominance and lengths of elongating replication forks
      progressing from single or clustered origins, as well as the sites of termination
      from two converging forks.

PMID- 23150445
TI  - Generation of p53-deficient induced pluripotent stem cells from mouse embryo
      fibroblasts.
AB  - Here we describe a method for generating induced pluripotent stem (iPS) cells
      from mouse embryonic fibroblasts (MEFs). Recombinant retroviruses carrying human
      transcription factors for Klf4, Oct3/4, Sox2, with or without c-Myc, are used to
      transduce early passage MEFs several times. Based on morphologic criteria, the
      resulting iPS colonies are picked manually at first, and then propagated and
      expanded by standard methods. iPS cells can then be differentiated into virtually
      any cell type or lineage, thus allowing for discoveries of new functions of p53
      and mutant p53.

PMID- 23150446
TI  - p53 actions on microRNA expression and maturation pathway.
AB  - The tumor suppressor p53 orchestrates multiple cellular pathways as a central
      node of anti-oncogenic programs in response to DNA damage, oncogene activation,
      and several stresses. In addition to the principal role as a transcription factor
      that transactivates many target genes involved in apoptosis and cell cycle
      control, p53 has been shown to exert various transactivation-independent effects
      both in the nucleus and in the cytoplasm. Diversity of p53 activities is further
      emphasized by the recent studies revealing the close interaction between the p53
      and microRNA (miRNA) world. We recently demonstrated that p53 promotes the
      processing of several primary miRNA transcripts through association with Drosha,
      a central RNase III in miRNA biogenesis, under DNA damage-inducing conditions. In
      contrast to wild-type p53, cancer-derived p53 mutants attenuate miRNA maturation.
      These findings reveal a novel aspect of p53 activities and suggest complex
      crosstalks between miRNA biogenesis and intracellular signaling pathways. In this
      chapter, we describe the methods for evaluation of the effects of p53 on miRNA
      expression, an interaction between pri-miRNA and Drosha complex, and pri-miRNA
      processing activity of the Drosha complex.

PMID- 23150447
TI  - Isolation and characterization of murine multipotent lung stem cells.
AB  - Cancer stem cells possess the ability to self-renew and differentiate into
      specific cells found in tumor types, a characteristic feature of normal
      multipotent stem cells. These cells harbor within the bulk of tumors and if the
      tumor suppressor p53 is mutated in these cells, can be more likely to cause
      relapse and metastasis by giving rise to new tumors. This new paradigm of
      oncogenesis has been observed in various cancers, including lung cancer.
      Determining the interaction of critical cellular pathways in the ontogeny of lung
      tumors is expected to lead to identification of molecular targets for effective
      therapeutic strategies. To achieve this, it is important to characterize and
      dissect the differences between the cancer cells with aberrant stem cell like
      properties and normal multipotent stem cells that contribute to regeneration.
      This could be accomplished by using cell surface markers unique for certain cell
      types by employing techniques such as flow cytometry and magnetic bead isolation.
      This chapter summarizes the isolation process of the resident stem cell Sca1
      (+ve), CD-45 (-ve), and CD-31 (-ve) populations for its potential use in
      assessing correlations between specific p53 gain of function phenotypes in
      different murine lung cancer models.

PMID- 23150448
TI  - Generation of p53 knock-down cell lines.
AB  - In order to study the functions of a cell's endogenous mutant p53, the p53
      protein levels must be knocked-down. Transient transfection of small interfering
      RNAs is one way to accomplish this. Another is the stable expression of short
      hairpin RNAs. This chapter presents a method by which a short hairpin RNA (shRNA)
      targeting p53 is inserted into the genome of a cell via lentivirus infection.
      These p53 knock-down cell lines are stable and may be grown long term for use in
      a wide range of applications.

PMID- 23150449
TI  - ChIP for identification of p53 responsive DNA promoters.
AB  - Chromatin immunoprecipitation assay (ChIP) has been frequently used to determine
      whether a transcriptional regulator can bind to a specific DNA element in the
      chromatin content of cells. Here, we describe a detailed protocol for this assay
      with hands-on tips based on our own experience in working on the transcriptional
      regulator and tumor suppressor p53.

PMID- 23150450
TI  - ChIP-on-chip to identify mutant p53 targets.
AB  - Chromatin immunoprecipitation (ChIP) followed by microarray hybridization (on
      chip) is a technique well suited for a comprehensive analysis of transcription
      factor binding sites, histone modification patterns, and nucleosome occupancy. It
      can be restricted to a subset of genes or regions but also expanded up to a
      genome-wide range yielding insight into the functional elements of gene
      regulatory networks. Mutant p53 proteins have lost their capacity to bind to its
      cognate binding sites, but it is well established that it has retained the
      ability to bind indirectly to DNA via other transcription factors and therefore
      change the expression of several target genes. The identification of those
      transcription factors and binding regions sheds light on how mutant p53 is able
      to exert oncogenic functions.

PMID- 23150451
TI  - ChIP sequencing to identify p53 targets.
AB  - Mutant p53 may activate target genes through the interaction of transcription
      factors or through histone modifications. Chromatin immunoprecipitation (ChIP) is
      a method commonly used to study these types of protein interactions. In order to
      generate a list of target genes that may be activated through this mechanism,
      ChIP sequencing may be used. ChIP sequencing involves the mass parallel
      sequencing of ChIP DNA fragments. We describe a method by which to prepare
      chromatin immunoprecipitation sequencing libraries and how to analyze sequencing
      data. In this procedure, prepared libraries have been sent to a core facility.
      The results have been verified using quantitative PCR.

PMID- 23150452
TI  - Catalytic and mechanistic insights of the low-temperature selective oxidation of
      methane over Cu-promoted Fe-ZSM-5.
AB  - The partial oxidation of methane to methanol presents one of the most challenging
      targets in catalysis. Although this is the focus of much research, until
      recently, approaches had proceeded at low catalytic rates (<10 h(-1)), not
      resulted in a closed catalytic cycle, or were unable to produce methanol with a
      reasonable selectivity. Recent research has demonstrated, however, that a system
      composed of an iron- and copper-containing zeolite is able to catalytically
      convert methane to methanol with turnover frequencies (TOFs) of over 14,000 h(-1)
      by using H(2)O(2) as terminal oxidant. However, the precise roles of the catalyst
      and the full mechanistic cycle remain unclear. We hereby report a systematic
      study of the kinetic parameters and mechanistic features of the process, and
      present a reaction network consisting of the activation of methane, the formation
      of an activated hydroperoxy species, and the by-production of hydroxyl radicals.
      The catalytic system in question results in a low-energy methane activation
      route, and allows selective C(1)-oxidation to proceed under intrinsically mild
      reaction conditions.

PMID- 23150453
TI  - Evaluating the impact of patient, tumor, and treatment characteristics on the
      development of jaw complications in patients treated for oral cancers: a SEER
      Medicare analysis.
AB  - BACKGROUND: Jaw complications, including osteoradionecrosis, are significant
      sequelae of radiation therapy (RT) for oral cancers. This study identifies the
      impact of patient, tumor, and treatment characteristics on the development of jaw
      complications in patients treated with RT. METHODS: The Surveillance,
      Epidemiology, and End Results (SEER)-Medicare database was used to identify
      patients treated with RT for oral cancers from 1999 to 2007. Jaw complications
      were identified by International Classification of Diseases 9th revision (ICD-9)
      diagnosis codes and/or related procedures using Current Procedural Terminology
      (CPT) and ICD-9 codes. RESULTS: A total of 1848 patients were identified. With a
      median follow-up of 2.5 years, 297 patients (16.1%) developed jaw complications:
      226 patients had a diagnosis, 41 patients had a procedure, and 30 patients had
      both. On multivariate analysis, female sex, lack of chemotherapy use, and fewer
      comorbidities were associated with a statistically significant increase in jaw
      complications. CONCLUSIONS: Even with modern techniques, jaw complications are a
      notable and potentially devastating side effect of RT for oral cancers.

PMID- 23150454
TI  - New insights into the biosynthesis of prenylated xanthones: Xptb from Aspergillus
      nidulans catalyses an O-prenylation of xanthones.
AB  - Gene-inactivation experiments have indicated that the putative prenyltransferase
      XptB from Aspergillus nidulans was likely to be responsible for the prenylation
      of 1,7-dihydroxy-6-methyl-8-hydroxymethylxanthone. Recently, it was suggested
      that this enzyme might also accept as substrate the benzophenone arugosin H,
      which is assumed to be a precursor of prenylated xanthones. In this study, five
      benzophenones and ten xanthones were incubated with purified recombinant XptB in
      the presence of dimethylallyl diphosphate (DMAPP). XptB accepted four xanthones
      as substrates, including the proposed natural substrate, and catalysed
      regiospecific O-prenylations at C-7 of the xanthone core. K(m) values in the
      range of 0.081-1.1 mM and turnover numbers (k(cat)) between 0.02 and 0.5 s(-1)
      were determined for the accepted xanthones. The kinetic parameters for DMAPP were
      found to be 0.024 mM (K(m)) and 0.13 s(-1) (k(cat)). Arugosin H was not accepted
      by XptB under the tested conditions. XptB was relatively specific towards its
      prenyl donor and did not accept geranyl or farnesyl diphosphate as substrate.
      Mn(2+) and Co(2+) strongly enhanced XptB activity (up to eightfold); this has not
      been reported before for prenyltransferases of the DMATS superfamily.

PMID- 23150455
TI  - Risk of cardiovascular disease in family members of young sudden cardiac death
      victims.
AB  - AIMS: Descriptive and genetic studies suggest that relatives of sudden cardiac
      death (SCD) victims have an increased risk of several cardiovascular diseases
      (CVDs). Given the severe consequences of undiagnosed CVD and the availability of
      effective treatment, the potential for prevention in this group is enormous if
      they do have an increased CVD risk. This nationwide prospective population-based
      cohort study described the risk of CVDs in relatives of young SCD victims,
      compared with the general population. METHODS AND RESULTS: All SCD victims aged 1
      35 years in Denmark, 2000-2006, were identified (n = 470), along with their first
      and second-degree relatives (n = 3073). We compared the incidence of CVD in
      those relatives with that in the background population using standardized
      incidence ratios (SIRs). The observed number of CVDs over 11 years of follow-up
      was 292, compared with 219 expected based on national rates [SIR 1.33, 95%
      confidence interval (CI) 1.19-1.50]. Risks varied significantly with age; the SIR
      for those <35 years was 3.53 (95% CI 2.65-4.69), compared with SIRs of 1.59 (95%
      CI 1.35-1.89) and 0.91 (95% CI 0.75-1.10) for those aged 35-60 years or >60
      years, respectively (P(homogeneity) < 0.0001). For first-degree relatives <35
      years, SIRs for ischaemic heart disease, cardiomyopathy, and ventricular
      arrhythmia were 5.99 (95% CI 1.95-0.13.98), 17.91 (95% CI 4.88-45.87), and 19.15
      (95% CI 7.70-39.45), respectively. CONCLUSION: CVDs co-aggregated significantly
      with SCD in families, with young first-degree relatives at greatest risk. Results
      clearly indicate that family members of young SCD victims should be offered
      comprehensive and systematic screening, with focus on the youngest relatives.

PMID- 23150456
TI  - New insights into the role of Runx1 in epithelial stem cell biology and
      pathology.
AB  - The transcription factor Runx1 has been studied in leukemia and blood for
      decades, but recently it has been also implicated in epithelial biology and
      pathology. Particularly in mouse skin Runx1 modulates Wnt signaling levels
      thereby regulating timely induction of hair follicle specification, proper
      maturation of the emerging adult hair follicle stem cells in embryogenesis, and
      timely stem cell (SC) activation during adult homeostasis. Moreover, Runx1 acts
      as a tumor promoter in mouse skin squamous tumor formation and maintenance,
      likely by repressing p21 and promoting Stat3 activation. Similarly, Runx1 is
      essential for oral epithelium tumorigenesis mediated in mice by Ras, and for
      growth of three kinds of human epithelial cancer cells. In contrast, Runx1 has a
      tumor suppressor function in the mouse intestine and shows tumor subtype specific
      behavior in human breast cancer. Multiple studies revealed Runx1 SNPs to be
      associated with human cancers and autoimmune disease. With this information as
      background, the field is poised for functional and mechanistic studies to
      elucidate the role of Runx1 in formation and/or progression of epithelial-based
      human disease.

PMID- 23150457
TI  - Design of alginate-based aerogel for nonsteroidal anti-inflammatory drugs
      controlled delivery systems using prilling and supercritical-assisted drying.
AB  - In this study, a novel preparation method for alginate-based aerogels charged
      with nonsteroidal anti-inflammatory drugs (NSAIDs) was developed using prilling
      in combination with supercritical fluid technique. Nanoporous carriers were
      prepared by laminar jet breakup of drug/alginate solutions or suspensions
      followed by cross-linking in ethanol or aqueous CaCl(2) solutions, water
      replacement, and supercritical-CO(2) -assisted drying. A substantial drug loss
      was observed for highly soluble ketoprofen lysinate, whereas encapsulation
      efficiency was satisfying for slightly soluble ketoprofen. The tandem technique
      successfully produced almost spherical aerogels (sphericity coefficient 0.97
      0.99) in narrow size distribution with reduced particle shrinkage and smooth
      surface (surface roughness 1.10-1.13); the internal porous texture of the parent
      hydrogels was preserved and appeared as a network of nanopores with diameters
      around 200 nm. Drug release profiles were monitored using a pH change method to
      evaluate the possible application of the aerogels as fast dissolving NSAIDs
      formulation. Aqueous cross-linking led to aerogels encapsulating ketoprofen in
      the amorphous form and with an enhanced burst effect in simulated gastric fluid
      (75% in 30 min), whereas ethanol cross-linking produced aerogels embedding drug
      in crystal clusters with slower dissolution rate. The system appears an
      interesting potential carrier for the fast delivery of slightly soluble drugs in
      the upper gastrointestinal tract.

PMID- 23150458
TI  - A two-stage molecular retractable cable featuring push-button and rotary two-way
      switching modes.
AB  - A molecular cage based [2]rotaxane is reported in which the linear thread
      component can be elongated and contracted in a stepwise manner, mimicking a two
      stage retractable cable that can be operated in both push-button (free-selection)
      and rotary (continuous-change) modes, depending on the choice of reagents.

PMID- 23150459
TI  - [Particuliarities of immunisation in the elderly].

PMID- 23150460
TI  - Localization of phenolics in phloem parenchyma cells of Norway spruce (Picea
      abies).
AB  - Norway spruce (Picea abies) bark contains specialized phloem parenchyma cells
      that swell and change their contents upon attack by the bark beetle Ips
      typographus and its microbial associate, the blue stain fungus Ceratocystis
      polonica. These cells exhibit bright autofluorescence after treatment with
      standard aldehyde fixatives, and so have been postulated to contain phenolic
      compounds. Laser microdissection of spruce bark sections combined with cryogenic
      NMR spectroscopy demonstrated significantly higher concentrations of the stilbene
      glucoside astringin in phloem parenchyma cells than in adjacent sieve cells.
      After infection by C. polonica, the flavonoid (+)-catechin also appeared in
      phloem parenchyma cells and there was a decrease in astringin content compared to
      cells from uninfected trees. Analysis of whole-bark extracts confirmed the
      results obtained from the cell extracts and revealed a significant increase in
      dimeric stilbene glucosides, both astringin and isorhapontin derivatives
      (piceasides A to H), in fungus-infected versus uninfected bark that might explain
      the reduction in stilbene monomers. Phloem parenchyma cells thus appear to be a
      principal site of phenolic accumulation in spruce bark.

PMID- 23150461
TI  - Endometrial cancer: utility of diffusion-weighted magnetic resonance imaging with
      background body signal suppression at 3T.
AB  - PURPOSE: To prospectively assess the usefulness of diffusion-weighted magnetic
      resonance imaging (MRI) with background body signal suppression (DWIBS) at 3T for
      the preoperative evaluation of endometrial cancer. MATERIALS AND METHODS: Fifty
      two consecutive patients with biopsy-proven endometrial cancer were examined with
      a 3T MR scanner, followed by a hysterectomy. MR examinations included T2-weighted
      (T2WI), DWIBS, and dynamic contrast-enhanced T1-weighted imaging (DCEI). The
      apparent diffusion coefficient (ADC) was calculated in the tumor and normal
      myometrium. According to tumor grade, the mean ADC of the tumor was analyzed. The
      depth of myometrial invasion was independently assessed by two radiologists for
      three MRI datasets on a five-point scale. RESULTS: The mean ADC of the tumors was
      significantly lower than that of normal myometrium (P < 0.001). The mean ADC of
      grades 2 or 3 was significantly lower than grade 1 (P < 0.01). For predicting
      myometrial invasion, the specificity, accuracy, and area under the curve of
      combined T2WI and DWIBS in both readers were similar to DCEI (P > 0.05).
      Interreader agreement in all MRI datasets was excellent. CONCLUSION: DWIBS at 3T
      has potential for being an effective method for the preoperative evaluation of
      endometrial cancer.

PMID- 23150462
TI  - The current state of bone loss research: data from spaceflight and microgravity
      simulators.
AB  - Bone loss is a well documented phenomenon occurring in humans both in short- and
      in long-term spaceflights. This phenomenon can be also reproduced on the ground
      in human and animals and also modeled in cell-based analogs. Since space flights
      are infrequent and expensive to study the biomedical effects of microgravity on
      the human body, much of the known pathology of bone loss comes from experimental
      studies. The most commonly used in vitro simulators of microgravity are
      clinostats while in vivo simulators include the bed rest studies in humans and
      hindlimb unloading experiments in animals. Despite the numerous reports that have
      documented bone loss in wide ranges in multiple crew members, the pathology
      remains a key concern and development of effective countermeasures is still a
      major task. Thus far, the offered modalities have not shown much success in
      preventing or alleviating bone loss in astronauts and cosmonauts. The objective
      of this review is to capture the most recent research on bone loss from
      spaceflights, bed rest and hindlimb unloading, and in vitro studies utilizing
      cellular models in clinostats. Additionally, this review offers projections on
      where the research has to focus to ensure the most rapid development of effective
      countermeasures.

PMID- 23150463
TI  - On the catalytic mechanism of (S)-2-hydroxypropylphosphonic acid epoxidase
      (HppE): a hybrid DFT study.
AB  - The mechanism of oxidative epoxidation catalyzed by HppE, which is the ultimate
      step in the biosynthesis of fosfomycin, was studied by using hybrid DFT quantum
      chemistry methods. An active site model used in the computations was based on the
      available crystal structure for the HppE-Fe(II)-(S)-HPP complex and it comprised
      first-shell ligands of iron as well as second-shell polar groups interacting with
      the substrates. The reaction energy profiles were constructed for three a priori
      plausible mechanisms proposed in the literature, and it was found that the most
      likely scenario for the native substrate, that is, (S)-HPP, involves generation
      of the reactive Fe(III)-O./Fe(IV)=O species, which is responsible for the C-H
      bond-cleavage. At the subsequent reaction stage, the OH-rebound, which would lead
      to a hydroxylated product, is prevented by a fast protonation of the OH ligand
      and, as a result, ring closure is the energetically preferred step. For the R
      enantiomer of the substrate ((R)-HPP), which is oxidized to a keto product,
      comparable barrier heights were found for the C-H bond activation by both the
      Fe(III)-O(2). and Fe(IV)=O species.

PMID- 23150464
TI  - The effect of relative humidity on the physical properties of two melibiose
      monohydrate batches with differing particle size distributions and surface
      properties.
AB  - Melibiose monohydrate has shown promise when employed as a pharmaceutical
      excipient, but its physical properties have not been adequately characterized.
      Therefore, two different melibiose monohydrate batches were analyzed as received
      or after storage under different relative humidity (RH) atmospheres. The particle
      size distributions and specific surface areas of the two batches were shown to
      differ considerably, which also had an effect on their water sorption tendencies
      and on the intermolecular structure of melibiose after storage. The relatively
      large primary particles that were more abundant in one of the batches were shown
      to possess a porous surface structure, and water evaporation from them occurred
      in two phases when heated. Furthermore, storing the batch with smaller mean
      particle size under dry conditions affected the crystal structure and molecular
      vibrations of the sample more than in the case of the batch with larger mean
      particle size. It was concluded that the physical properties of melibiose
      monohydrate after storage at different RH atmospheres is largely governed by the
      primary particle size and porosity.

PMID- 23150465
TI  - Photophysics of Schiff bases: theoretical study of salicylidene methylamine.
AB  - The proton-transfer reaction in a model aromatic Schiff base, salicylidene
      methylamine (SMA), in the ground and in the lowest electronically-excited singlet
      states, is theoretically analyzed with the aid of second-order approximate
      coupled-cluster model CC2, time-dependent density functional theory (TD-DFT)
      using the Becke, three-parameter Lee-Yang-Parr (B3LYP) functional, and complete
      active space perturbation theory CASPT2 electronic structure methods. Computed
      vertical-absorption spectra for the stable ground-state isomers of SMA fully
      confirm the photochromism of SMA. The potential-energy profiles of the ground and
      the lowest excited singlet state are calculated and four photophysically relevant
      isomeric forms of SMA; alpha, beta, gamma, and delta are discussed. The
      calculations indicate two S(1)/S(0) conical intersections which provide non
      adiabatic gates for a radiationless decay to the ground state. The photophysical
      scheme which emerges from the theoretical study is related to recent experimental
      results obtained for SMA and its derivatives in the low-temperature argon
      matrices (J. Grzegorzek, A. Filarowski, Z. Mielke, Phys. Chem. Chem. Phys. 2011,
      13, 16596-16605). Our results suggest that aromatic Schiff bases are potential
      candidates for optically driven molecular switches.

PMID- 23150467
TI  - Reactivity of a frustrated lewis pair and small-molecule activation by an
      isolable Arduengo carbene-B{3,5-(CF3)2C6H3}3 complex.
AB  - Tris[3,5-bis(trifluoromethyl)phenyl]borane reacts with the sterically demanding
      Arduengo carbenes 1,3-di-tert-butylimidazolin-2-ylidene and 1,3-bis(2,6
      diisopropylphenyl)imidazolin-2-ylidene to form isolable normal adducts. In the
      case of 1,3-di-tert-butylimidazolin-2-ylidene, the adduct exhibits dynamic
      behaviour in solution and frustrated-Lewis-pair (FLP) reactivity. Fast cleavage
      of dihydrogen and THF, the C-H activation of phenylacetylene, and carbon dioxide
      fixation were achieved by using solutions of this adduct in benzene. This adduct
      is stable at room temperature in the absence of suitable substrates; however,
      thermal rearrangement into an abnormal carbene-borane adduct can be observed. In
      contrast, the 1,3-bis(2,6-diisopropylphenyl)imidazolin-2-ylidene adduct exhibits
      no evidence of FLP reactivity or of dissociation in solution. DFT calculations
      confirmed the experimental behaviour and stability of these carbene-borane
      adducts.

PMID- 23150466
TI  - Subject tolerance of 7 T MRI examinations.
AB  - PURPOSE: To determine the subjective experiences and the sources of discomfort
      for subjects undergoing 7 T magnetic resonance imaging (MRI) examinations on a
      whole-body 7 T system in a hospital setting MATERIALS AND METHODS: A postscan
      survey was filled out by 101 healthy subjects who participated in a 7 T
      examination. All participants answered questions regarding different potential
      sensations of discomfort including dizziness, claustrophobia, and scanner noise.
      RESULTS: Dizziness was reported most frequently, with 34% of subjects
      experiencing dizziness while moving into the scanner and 30% while moving out of
      the magnet. Scanner noise was also frequently mentioned as uncomfortable (33% of
      the subjects). In 11% of the cases a metallic taste was reported. The overall
      experience was rated by 3% as unpleasant, 51% as neutral, and 46% as pleasant.
      CONCLUSION: The reported side effects are larger than previously reported for
      lower field strengths. However, overall, 7 T examinations are well tolerated,
      with only 3% of subjects rating it as unpleasant. These results agree well with
      previous in-depth studies, and provide further evidence that 7 T MRI would be
      accepted by patients in clinical practice.

PMID- 23150468
TI  - Biocompatible microemulsion modifies the pharmacokinetic profile and
      cardiotoxicity of doxorubicin.
AB  - Doxorubicin (DOX) is an anthracycline antibiotic with a broad antitumor spectrum.
      However, the clinical use of DOX is limited because of its cardiotoxicity, a dose
      dependent effect. Colloidal drug delivery systems, such as microemulsions (MEs),
      allow the incorporation of drugs, modifying the pharmacokinetic (PK) profile and
      toxic effects. In this study, we evaluated the PK profile and cardiotoxicity of a
      new DOX ME (DOX-ME). The PK profile of DOX-ME was determined and compared with
      that of the conventional DOX after single-dose administration (6 mg/kg,
      intravenous) in male Wistar rats (n = 12 per group). The cardiotoxicity of DOX
      formulations was evaluated by serum creatine kinase MB (CKMB) activity in both
      animal groups before and after drug administration. The plasma DOX measurements
      were performed by high-performance liquid chromatography with fluorescence
      detection, and the CKMB levels were assayed using the CKMB Labtest(r) kit. The ME
      system showed a significant increase in plasma DOX concentrations and lower
      distribution volume when compared with conventional DOX. Serum CKMB activity
      increased after conventional DOX administration but was unchanged in the DOX-ME
      group. These results demonstrate modifications in drug access to susceptible
      sites using DOX-ME. DOX-ME displayed features that make it a promising system for
      future therapeutic application.

PMID- 23150469
TI  - Dopamine agonists and delusional jealousy in Parkinson's disease: a cross
      sectional prevalence study.
AB  - BACKGROUND: Delusional jealousy (DJ) has been described in patients with
      Parkinson's disease (PD) on dopaminergic therapy, but a role for dopaminergic
      therapy in DJ has not been established. METHODS: The current cross-sectional
      study on DJ investigated its association with dopaminergic therapies compared
      with their associations with hallucinations and its prevalence in PD patients.
      Eight hundred five consecutive patients with PD were enrolled between January
      2009 and June 2010. RESULTS: DJ was identified in 20 patients (2.48%) and
      hallucinations in 193 patients (23.98%). In the multivariate logistic regression
      analyses, dopamine agonists were significantly associated with DJ (odds ratio,
      18.1; 95% CI, 3.0-infinity; P = .0002) but not with hallucinations (odds ratio,
      0.73; 95% CI, 0.49-1.10; P = .133). CONCLUSIONS: These findings suggest that
      dopamine agonist treatment represents a risk factor for DJ in PD independent of
      the presence of a dementing disorder, and the presence of this additional
      nonmotor side effect should be investigated in this clinical population.

PMID- 23150470
TI  - Effects of age and gender on neuroanatomical volumes.
AB  - PURPOSE: To investigate age-related differences, gender differences, and age-by
      gender interactions on the volumes of 18 neuroanatomical structures, with a large
      sample at a single institution. MATERIALS AND METHODS: A total of 861 normal
      subjects (mean age = 56.1 +/- 9.8 years, age range = 24.0-84.8 years) were
      included in this study. All subjects were scanned at 3.0 T. Measurement of the 18
      neuroanatomical volumes was performed with FreeSurfer v. 4.5. Differences in
      volumes of neuroanatomical structures were tested using analysis of covariance
      with intracranial volume-normalized volume as the dependent variable, and
      independent variables of age, sex, age * sex, age * age, age * age * sex, and
      scanner. Nonsignificant higher-order terms were removed sequentially from the
      model. A P value of < 0.0028 (=0.5/18) was considered to indicate a statistically
      significant difference. RESULTS: All neuroanatomical volumes, except for the
      caudate nucleus, pallidum, and 4th ventricle, were significantly related to age
      (linearly or quadratically). Significant gender differences were found in all
      neuroanatomical volumes, except for cerebral white matter, cerebellar cortex,
      caudate nucleus, and amygdala. No neuroanatomical volume showed a significant
      interaction between age (age * age) and gender. CONCLUSION: Our results showed
      age and gender effects on neuroanatomical volumes, and indicate no gender
      difference in the aging process of neuroanatomical volumes.

PMID- 23150471
TI  - Stereo- and regioselective direct multi-deuterium-labeling methods for sugars.
AB  - Deuterium-labeled sugars can be utilized as powerful tools for the architectural
      analyses of high-sugar-containing molecules represented by the nucleic acids and
      glycoproteins, and chiral building blocks for the syntheses of new drug
      candidates (heavy drugs) due to their potential characteristics, such as
      simplifying the (1)H NMR spectra and the stability of C-D bonds compared with C-H
      bonds. We have established a direct and efficient synthetic method of deuterated
      sugars from non-labeled sugars by using the heterogeneous Ru/C-catalyzed H-D
      exchange reaction in D(2)O under a hydrogen atmosphere with perfect chemo- and
      stereoselectivities. The direct H-D exchange reaction can selectively proceed on
      carbons adjacent to the free hydroxyl groups, and the deuterium labeling of
      various pyranosides (such as glucose and disaccharides), as well as furanosides,
      represented by ribose and deoxyribose was realized. Furthermore, the desired
      number of deuterium atoms can be freely incorporated into selected positions by
      the site-selective protection of the hydroxyl groups using acetal-type protective
      groups because the deuterium exchange reaction never proceeds on positions
      adjacent to the protected hydroxyl groups.

PMID- 23150472
TI  - Childhood constipation.

PMID- 23150474
TI  - Let us now praise famous men and women.

PMID- 23150473
TI  - Efficacy and safety of novel oral anticoagulants for treatment of acute venous
      thromboembolism: direct and adjusted indirect meta-analysis of randomised
      controlled trials.
AB  - OBJECTIVE: To critically review the effectiveness of the novel oral
      anticoagulants (rivaroxaban, dabigatran, ximelagatran, and apixaban) in the
      treatment of acute venous thromboembolism. DESIGN: Systematic review and random
      effects meta-analysis. Data were extracted independently by two investigators. An
      adjusted indirect comparison was performed to compare between novel oral
      anticoagulants. DATA SOURCES: Medline, Embase, and Cochrane Library (from
      inception to April 2012). Hand searching of relevant scientific works and contact
      with experts. STUDY SELECTION: Randomised controlled trials of novel oral
      anticoagulants compared with vitamin K antagonists for acute venous
      thromboembolism. Selected outcomes were recurrent events, major bleeding, and all
      cause mortality. RESULTS: Nine studies met our inclusion criteria, involving
      16,701 patients evaluated for efficacy and 16,611 for safety. Data were
      stratified according to different novel oral anticoagulants. For recurrent acute
      venous thromboembolism, there were no significant differences in events rates
      between any of the anticoagulants and conventional treatment (rivaroxaban (four
      studies): relative risk 0.85, 95% confidence interval 0.55 to 1.31; dabigatran
      (two studies): 1.09, 0.76 to 1.57; ximelagatran (two studies): 1.06, 0.62 to
      1.80; and apixaban (one study): 0.98, 0.20 to 4.79). Rivaroxaban reduced the risk
      of major bleeding compared with conventional treatment (0.57, 0.39 to 0.84),
      whereas other novel oral anticoagulants did not (0.76 (0.49 to 1.18) for
      dabigatran; 0.54 (0.28 to 1.03) for ximelagatran; 2.95 (0.12 to 71.82) for
      apixaban). For all cause mortality there were no significant differences between
      the novel oral anticoagulants and conventional treatment (0.96 (0.72 to 1.27) for
      rivaroxaban; 1.00 (0.67 to 1.50) for dabigatran; 0.67 (0.42 to 1.08) for
      ximelagatran; 6.89 (0.36 to 132.06) for apixaban). The adjusted indirect
      comparison between rivaroxaban and dabigatran did not show superiority of either
      drug over the others for major bleeding (0.75, 0.41 to 1.34) or the other
      endpoints. CONCLUSIONS: Compared with vitamin K antagonists, the novel oral
      anticoagulants had a similar risk of recurrence of acute venous thromboembolism
      and all cause mortality, though rivaroxaban was associated with a reduced risk of
      bleeding.

PMID- 23150475
TI  - Active adults live longer.

PMID- 23150476
TI  - Therapeutic manipulation of HDL fails to benefit adults with heart disease.

PMID- 23150477
TI  - Privatisation in Spain provokes protests among doctors.

PMID- 23150478
TI  - Malaria vaccine trial shows lower efficacy in younger than in older infants.

PMID- 23150479
TI  - Awareness of symptoms could eliminate 5600 late cancer diagnoses in England each
      year.

PMID- 23150480
TI  - MRSA in waste treatment water poses potential risk.

PMID- 23150481
TI  - London medical education boss quits amid plans to break up deanery.

PMID- 23150482
TI  - GPs will not negotiate with government "with a gun to their head," GP leader
      says.

PMID- 23150483
TI  - Italian police arrest nine cardiologists.

PMID- 23150484
TI  - A systematic multitechnique approach for detection and characterization of
      reversible self-association during formulation development of therapeutic
      antibodies.
AB  - In addition to controlling typical instabilities such as physical and chemical
      degradations, understanding monoclonal antibodies' (mAbs) solution behavior is a
      key step in designing and developing process and formulation controls during
      their development. Reversible self-association (RSA), a unique solution property
      in which native, reversible oligomeric species are formed as a result of the
      noncovalent intermolecular interactions has been recognized as a developability
      risk with the potential to negatively impact manufacturing, storage stability,
      and delivery of mAbs. Therefore, its identification, characterization, and
      mitigation are key requirements during formulation development. Considering the
      large number of available analytical methods, choice of the employed technique is
      an important contributing factor for successful investigation of RSA. Herein, a
      multitechnique (dynamic light scattering, multiangle static light scattering, and
      analytical ultracentrifugation) approach is employed to comprehensively
      characterize the self-association of a model immunoglobulin G1 molecule. Studies
      herein discuss an effective approach for detection and characterization of RSA
      during biopharmaceutical development based on the capabilities of each technique,
      their complementarity, and more importantly their suitability for the stage of
      development in which RSA is investigated.

PMID- 23150485
TI  - Induction of multidrug resistance transporter ABCG2 by prolactin in human breast
      cancer cells.
AB  - The multidrug transporter, breast cancer resistance protein, ABCG2, is up
      regulated in certain chemoresistant cancer cells and in the mammary gland during
      lactation. We investigated the role of the lactogenic hormone prolactin (PRL) in
      the regulation of ABCG2. PRL dose-dependently induced ABCG2 expression in T-47D
      human breast cancer cells. This induction was significantly reduced by short
      interfering RNA-mediated knockdown of Janus kinase 2 (JAK2). Knockdown or
      pharmacologic inhibition of the down-stream signal transducer and activator of
      transcription-5 (STAT5) also blunted the induction of ABCG2 by PRL, suggesting a
      role for the JAK2/STAT5 pathway in PRL-induced ABCG2 expression. Corroborating
      these findings, we observed PRL-stimulated STAT5 recruitment to a region
      containing a putative gamma-interferon activation sequence (GAS) element at -434
      base pairs upstream of the ABCG2 transcription start site. Introduction of a
      single mutation to the -434 GAS element significantly attenuated PRL-stimulated
      activity of a luciferase reporter driven by the ABCG2 gene promoter and 5'
      flanking region containing the -434 GAS motif. In addition, this GAS element
      showed strong copy number dependency in its response to PRL treatment.
      Interestingly, inhibitors against the mitogen-activated protein kinase and
      phosphoinositide-3-kinase signaling pathways significantly decreased the
      induction of ABCG2 by PRL without altering STAT5 recruitment to the GAS element.
      We conclude that the JAK2/STAT5 pathway is required but not sufficient for the
      induction of ABCG2 by PRL.

PMID- 23150487
TI  - Obtusilactone B from Machilus Thunbergii targets barrier-to-autointegration
      factor to treat cancer.
AB  - Targeting specific molecules is a promising cancer treatment because certain
      types of cancer cells are dependent on specific oncogenes. This strategy led to
      the development of therapeutics that use monoclonal antibodies or small-molecule
      inhibitors. However, the continued development of novel molecular targeting
      inhibitors is required to target the various oncogenes associated with the
      diverse types and stages of cancer. Obtusilactone B is a butanolide derivative
      purified from Machilus thunbergii. In this study, we show that obtusilactone B
      functions as a small-molecule inhibitor that causes abnormal nuclear envelope
      dynamics and inhibits growth by suppressing vaccinia-related kinase 1 (VRK1)
      mediated phosphorylation of barrier-to-autointegration factor (BAF). BAF is
      important in maintaining lamin integrity, which is closely associated with
      diseases that include cancer. Specific binding of obtusilactone B to BAF
      suppressed VRK1-mediated BAF phosphorylation and the subsequent dissociation of
      the nuclear envelope from DNA that allows cells to progress through the cell
      cycle. Obtusilactone B potently induced tumor cell death in vitro, indicating
      that specific targeting of BAF to block cell cycle progression can be an
      effective anticancer strategy. Our results demonstrate that targeting a major
      constituent of the nuclear envelope may be a novel and promising alternative
      approach to cancer treatment.

PMID- 23150489
TI  - More than 1500 patients recalled after team finds serious shortcomings in
      surgeon's work.

PMID- 23150488
TI  - Influence of drug lipophilicity on drug release from sclera after iontophoretic
      delivery of mixed micellar carrier system to human sclera.
AB  - Mixed micelles prepared using sodium taurocholate (TA) and egg lecithin (LE) were
      previously found to be an effective carrier for sustained release of a poorly
      water-soluble drug in transscleral iontophoretic delivery. The objectives of the
      present study were to investigate the effects of drug lipophilicity upon micellar
      carrier solubilization potential and drug release profiles from the sclera after
      iontophoretic delivery of model lipophilic drugs dexamethasone (DEX),
      triamcinolone acetonide (TRIAM), and beta-estradiol (E2beta) with a mixed
      micellar carrier system of TA-LE (1:1 mole ratio). In this study, the micellar
      carrier system was characterized for drug solubilization. The micelles
      encapsulating these drugs were evaluated for transscleral passive and 2-mA
      iontophoretic delivery (both cathodal and anodal) and drug release from excised
      human sclera in vitro. The results show that drug solubility enhancement of the
      micellar carrier system increased with increasing drug lipophilicity. The more
      lipophilic drugs E2beta and TRIAM displayed slower drug release from the sclera
      compared with the less lipophilic drug DEX after iontophoretic drug delivery with
      the mixed micelles. These results suggest that the combination of transscleral
      iontophoresis and micellar carriers is more effective in sustaining transscleral
      delivery of the more lipophilic drugs studied in this investigation.

PMID- 23150486
TI  - Writing and rewriting the epigenetic code of cancer cells: from engineered
      proteins to small molecules.
AB  - The epigenomic era has revealed a well-connected network of molecular processes
      that shape the chromatin landscape. These processes comprise abnormal methylomes,
      transcriptosomes, genome-wide histone post-transcriptional modifications
      patterns, histone variants, and noncoding RNAs. The mapping of these processes in
      large scale by chromatin immunoprecipitation sequencing and other methodologies
      in both cancer and normal cells reveals novel therapeutic opportunities for
      anticancer intervention. The goal of this minireview is to summarize
      pharmacological strategies to modify the epigenetic landscape of cancer cells.
      These approaches include the use of novel small molecule inhibitors of epigenetic
      processes specifically deregulated in cancer cells and the design of engineered
      proteins able to stably reprogram the epigenetic code in cancer cells in a way
      that is similar to normal cells.

PMID- 23150490
TI  - The rise in growth hormone during starvation does not serve to maintain glucose
      levels or lean mass but is required for appropriate adipose tissue response in
      female mice.
AB  - In mice, GH levels rise in response to short-term fasting or starvation (food
      restriction to 40% of ad libitum intake), similar to that which occurs in humans
      in response to fasting or anorexia. Recent studies using acyl-ghrelin knockout
      mice have suggested that the rise in GH during food restriction is essential to
      support glucose levels. To directly test this hypothesis, adult-onset isolated GH
      deficient (AOiGHD) mice and their GH-replete littermate controls were provided
      40% of ad libitum food intake for 11 d. As previously shown, food restriction
      increased GH levels in controls, and this response was not observed in AOiGHD
      mice. In both controls and AOiGHD, food restriction resulted in an initial
      decline in glucose, which stabilized to 82-85% of ad libitum-fed values by d 2.
      In addition, loss of lean mass in response to food restriction was not altered by
      GH status. However, the loss of fat mass and the associated rise in circulating
      free fatty acids and ketones was blunted in starved AOiGHD mice compared with
      controls. Taken together, these results suggest a rise of GH during starvation is
      not required to support glucose levels and muscle mass but may be important in
      supporting fat mobilization.

PMID- 23150491
TI  - Maternal and fetal exposure to bisphenol a is associated with alterations of
      thyroid function in pregnant ewes and their newborn lambs.
AB  - The putative thyroid-disrupting properties of bisphenol A (BPA) highlight the
      need for an evaluation of fetal exposure and its consequence on the
      mother/newborn thyroid functions in models relevant to human. The goals of this
      study were to characterize in sheep a relevant model for human pregnancy and
      thyroid physiology, the internal exposures of the fetuses and their mothers to
      BPA and its main metabolite BPA-glucuronide (Gluc), and to determine to what
      extent it might be associated with thyroid disruption. Ewes were treated with BPA
      [5 mg/(kg . d) sc] or vehicle from d 28 until the end of pregnancy. Unconjugated
      BPA did not appear to accumulate in pregnant ewes, and its concentration was
      similar in the newborns and their mothers (0.13 +/- 0.02 and 0.18 +/- 0.03
      nmol/ml in cord and maternal blood, respectively). In amniotic fluid and cord
      blood, BPA-Gluc concentrations were about 1300-fold higher than those of BPA.
      Total T(4) concentrations were decreased in BPA-treated pregnant ewes and in the
      cord and the jugular blood of their newborns (30% decrease). A similar difference
      was observed for free T(4) plasma concentrations in the jugular blood of the
      newborns. Our results show in a long-gestation species with a similar regulatory
      scheme of thyroid function as humans that BPA in utero exposure can be associated
      with hypothyroidism in the newborns. If such an effect were to be confirmed for a
      more relevant exposure scheme to BPA, this would constitute a major issue for BPA
      risk assessment.

PMID- 23150492
TI  - GnRH neuronal migration and olfactory bulb neurite outgrowth are dependent on FGF
      receptor 1 signaling, specifically via the PI3K p110alpha isoform in chick
      embryo.
AB  - Fibroblast growth factor (FGF) signaling is essential for both olfactory bulb
      (OB) morphogenesis and the specification, migration, and maturation of the GnRH
      secreting neurons. Disruption of FGF signaling contributes to Kallmann syndrome
      characterized by both anosmia and sexual immaturity. However, several unanswered
      questions remain as to which specific FGF receptor (FGFR)-1 signaling pathways
      are necessary for OB and GnRH neuronal development. Here, using pharmacological
      phosphatidylinositol 3-kinase (PI3K) isoform-specific inhibitors, we demonstrate
      a central role for the PI3K p110alpha isoform as a downstream effector of FGFR1
      signaling for both GnRH neuronal migration and OB development. We show that
      signaling via the PI3K p110alpha isoform is required for GnRH neuronal migration
      in explant cultures of embryonic day (E) 4 chick olfactory placodes. We also show
      that in ovo administration of LY294002, a global PI3K inhibitor as well as an
      inhibitor to the PI3K p110alpha isoform into the olfactory placode of E3 chick
      embryo impairs GnRH neuronal migration toward the forebrain. In contrast, in ovo
      PI3K inhibitor treatment produced no obvious defects on primary olfactory sensory
      neuron axonal targeting and bundle formation. We also demonstrate that anosmin-1
      and FGF2 induced neuronal migration of immortalized human embryonic GnRH
      neuroblast cells (FNC-B4-hTERT) is mediated by modulating FGFR1 signaling via the
      PI3K p110alpha isoform, specifically through phosphorylation of the PI3K
      downstream effectors, Akt and glycogen synthase kinase-3beta. Finally, we show
      that neurite outgrowth and elongation of OB neurons in E10 chick OB explants are
      also dependent on the PI3K p110alpha isoform downstream of FGFR1. This study
      provides mechanistic insight into the etiology of Kallmann syndrome.

PMID- 23150493
TI  - Susceptibility to fatty acid-induced beta-cell dysfunction is enhanced in
      prediabetic diabetes-prone biobreeding rats: a potential link between beta-cell
      lipotoxicity and islet inflammation.
AB  - beta-Cell lipotoxicity is thought to play an important role in the development of
      type 2 diabetes. However, no study has examined its role in type 1 diabetes,
      which could be clinically relevant for slow-onset type 1 diabetes. Reports of
      enhanced cytokine toxicity in fat-laden islets are consistent with the hypothesis
      that lipid and cytokine toxicity may be synergistic. Thus, beta-cell lipotoxicity
      could be enhanced in models of autoimmune diabetes. To determine this, we
      examined the effects of prolonged free fatty acids elevation on beta-cell
      secretory function in the prediabetic diabetes-prone BioBreeding (dp-BB) rat, its
      diabetes-resistant BioBreeding (dr-BB) control, and normal Wistar-Furth (WF)
      rats. Rats received a 48-h iv infusion of saline or Intralipid plus heparin (IH)
      (to elevate free fatty acid levels ~2-fold) followed by hyperglycemic clamp or
      islet secretion studies ex vivo. IH significantly decreased beta-cell function,
      assessed both by the disposition index (insulin secretion corrected for IH
      induced insulin resistance) and in isolated islets, in dp-BB, but not in dr-BB or
      WF, rats, and the effect of IH was inhibited by the antioxidant N-acetylcysteine.
      Furthermore, IH significantly increased islet cytokine mRNA and plasma cytokine
      levels (monocyte chemoattractant protein-1 and IL-10) in dp-BB, but not in dr-BB
      or WF, rats. All dp-BB rats had mononuclear infiltration of islets, which was
      absent in dr-BB and WF rats. In conclusion, the presence of insulitis was
      permissive for IH-induced beta-cell dysfunction in the BB rat, which suggests a
      link between beta-cell lipotoxicity and islet inflammation.

PMID- 23150495
TI  - Ablation of Egr2-positive cells in male mouse anterior pituitary leads to
      atypical isolated GH deficiency.
AB  - In this study, we have investigated the expression and function of the
      transcription factor early growth response factor 2 (Egr2)/Krox20 in the
      developing anterior pituitary. Egr2 is initially expressed in all differentiating
      hormonal cells types, but its expression is mostly restricted to the somatotroph
      lineage after birth. Egr2 knockout results in anterior pituitary hypoplasia.
      However, the analysis of a conditional mutant demonstrates that this phenotype
      does not originate from a lack of Egr2 expression in the pituitary. Using an Egr2
      allele driving a Cre-activable toxin gene, we performed a genetic ablation of
      Egr2-positive cells in the pituitary. During the postnatal period, this ablation
      leads to specific and progressive depletion of the somatotroph population,
      creating a novel model of early-onset isolated GH deficiency (GHD). Mutant
      animals were subjected to a complete metabolic analysis, revealing atypical and
      expected features. Consistent with an adult-onset isolated GHD model, mutant
      animals are hypoglycemic and display increased insulin sensitivity and glucose
      clearance. This latter phenotype is in contrast to the glucose intolerance
      observed in another early-onset GHD model. Surprisingly, increased insulin
      sensitivity is not accompanied by a modified balance between fat and lean
      tissues, but by reduced metabolic adaptability between glucose and lipid
      oxidation conditions. This suggests that the relationship between these metabolic
      features and insulin sensitivity should be reconsidered. In conclusion, our
      mutant may be a valuable genetic model with which to study the effects of long
      term GH deficiency, in conditions of normal pancreatic function and unaffected
      balance between fat and glucose metabolism.

PMID- 23150494
TI  - Release of norepinephrine in the preoptic area activates anteroventral
      periventricular nucleus neurons and stimulates the surge of luteinizing hormone.
AB  - The role of norepinephrine (NE) in regulation of LH is still controversial. We
      investigated the role played by NE in the positive feedback of estradiol and
      progesterone. Ovarian-steroid control over NE release in the preoptic area (POA)
      was determined using microdialysis. Compared with ovariectomized (OVX) rats,
      estradiol-treated OVX (OVX+E) rats displayed lower release of NE in the morning
      but increased release coincident with the afternoon surge of LH. OVX rats treated
      with estradiol and progesterone (OVX+EP) exhibited markedly greater NE release
      than OVX+E rats, and amplification of the LH surge. The effect of NE on LH
      secretion was confirmed using reverse microdialysis. The LH surge and c-Fos
      expression in anteroventral periventricular nucleus neurons were significantly
      increased in OVX+E rats dialyzed with 100 nm NE in the POA. After Fluoro-Gold
      injection in the POA, c-Fos expression in Fluoro-Gold/tyrosine hydroxylase
      immunoreactive neurons increased during the afternoon in the A2 of both OVX+E and
      OVX+EP rats, in the locus coeruleus (LC) of OVX+EP rats, but was unchanged in the
      A1. The selective lesion of LC terminals, by intracerebroventricular N-(2
      chloroethyl)-N-ethyl-2-bromobenzylamine, reduced the surge of LH in OVX+EP but
      not in OVX+E rats. Thus, estradiol and progesterone activate A2 and LC neurons,
      respectively, and this is associated with the increased release of NE in the POA
      and the magnitude of the LH surge. NE stimulates LH secretion, at least in part,
      through activation of anteroventral periventricular neurons. These findings
      contribute to elucidation of the role played by NE during the positive feedback
      of ovarian steroids.

PMID- 23150497
TI  - Raising price of alcohol in one Canadian province led to fall in drinking, finds
      study.

PMID- 23150496
TI  - The effect of fish matrix on the enzyme-linked immunosorbent assay of
      antibiotics.
AB  - BACKGROUND: The matrix effect is considered to be a problem in the immunoassay of
      foodstuffs. However, information on the interference from aquatic products, as
      well as the mechanism involved, is very limited. In this study, using three
      flatfishes (Scophthalmus maximus, Paralichthys olivaceus and Cymoglossus
      robustus) as samples, the effect of the fish matrix on the competitive indirect
      enzyme-linked immunosorbent assay (ci-ELISA) of antibiotic (norfloxacin) residues
      was investigated. The mechanism of the observed matrix effect is also
      preliminarily discussed. RESULTS: Within the working range of the calibration
      curves, a significant (P = 0.05) but irregular variation in the inhibition ratio
      was observed in the presence of fish extracts. Further experiments revealed that
      such a matrix effect could be caused by some water-soluble fish proteins with a
      wide range of molecular weight (from below 14.4 kDa to about 116.0 kDa), and the
      ions from fish muscles may also contribute to the interference. The results of
      western blotting indicated that some fish protein components might effectively
      bind with antibody reagents used. CONCLUSION: Significant interference in the
      immunoassay of norfloxacin was observed in the presence of fish matrix. Some
      proteins and ions were demonstrated to contribute to the matrix effect
      investigated. Although the detailed mechanism is still unclear, the non-specific
      interaction between fish proteins and immunoglobulin G (IgG) or horseradish
      peroxidase (HRP) labelled IgG was assumed to be an important source of the matrix
      effect in immunoassays.

PMID- 23150498
TI  - Effects on DPPH inhibition of egg-white protein polypeptides treated by pulsed
      electric field technology.
AB  - BACKGROUND: Egg-white protein polypeptides are potentially used as a functional
      ingredient in food products. In this study, the effects on DPPH inhibition of egg
      white protein polypeptides ranging from 10 to 30 kDa treated by pulsed electric
      field (PEF) technology were investigated. RESULTS: 2, 2-Diphenyl-1-picrylhydrazyl
      (DPPH) inhibition (%) was used to evaluate the antioxidant activity of
      polypeptides. In order to develop and optimize a pulsed electric field (PEF)
      mathematical model for improving the antioxidant activity, we have investigated
      three variables, including concentration (6, 8 and 10 mg mL(-1)), electric field
      intensity (10, 20 and 30 kV cm(-1)) and pulse frequency (2000, 2350 and 2700 Hz)
      and subsequently optimized them by response surface methodology (RSM). The
      concentration (8 mg mL(-1)), electric field intensity (10 kV cm(-1)) and pulse
      frequency (2000 Hz) were found to be the optimal conditions under which the DPPH
      inhibition increased 28.44%, compared to the sample without PEF treatment. Both
      near-infrared spectroscopy (NIR) and mid-infrared spectroscopy (MIR) were used to
      analyze the change of functional groups. CONCLUSION: The results showed that PEF
      technology could improve the antioxidant activity of antioxidant polypeptides
      from egg-white protein under the optimized conditions.

PMID- 23150499
TI  - Sale of out of hours care company for L48m brings GPs big profits.

PMID- 23150500
TI  - Contrast-enhanced intraoperative ultrasonography for vascular imaging of
      hepatocellular carcinoma: clinical and biological significance.
AB  - Abnormal tumor vascularity is one of the typical features of hepatocellular
      carcinoma (HCC). In this study, the significance of contrast-enhanced
      intraoperative ultrasonography (CEIOUS) images of HCC vasculature was evaluated
      by clinicopathological and gene expression analyses. We enrolled 82 patients who
      underwent curative hepatic resection for HCC with CEIOUS. Clinicopathological and
      gene expression analyses were performed according to CEIOUS vasculature patterns.
      CEIOUS images of HCC vasculatures were classified as reticular HCC or thunderbolt
      HCC. Thunderbolt HCC was significantly correlated with higher alpha-fetoprotein
      levels, tumor size, histological differentiation, portal vein invasion, and tumor
      node-metastasis stage, and these patients demonstrated a significantly poorer
      prognosis for both recurrence-free survival (P = 0.0193) and overall survival (P
      = 0.0362) compared with patients who had reticular HCC. Gene expression analysis
      revealed that a rereplication inhibitor geminin was significantly overexpressed
      in thunderbolt HCCs (P = 0.00326). In vitro knockdown of geminin gene reduced
      significantly the proliferation of human HCC cells. Immunohistochemical analysis
      confirmed overexpression of geminin protein in thunderbolt HCC (P < 0.0001).
      Multivariate analysis revealed geminin expression to be an independent factor in
      predicting poor survival in HCC patients (P = 0.0170). CONCLUSION: CEIOUS
      vascular patterns were distinctly identifiable by gene expression profiling
      associated with cellular proliferation of HCC and were significantly related to
      HCC progression and poor prognosis. These findings might be clinically useful as
      a determinant factor in the postoperative treatment of HCC.

PMID- 23150501
TI  - Renal sympathetic denervation provides ventricular rate control but does not
      prevent atrial electrical remodeling during atrial fibrillation.
AB  - Renal denervation (RDN) reduces renal efferent and afferent sympathetic activity
      thereby lowering blood pressure in resistant hypertension. The effect of
      modulation of the autonomic nervous system by RDN on atrial electrophysiology and
      ventricular rate control during atrial fibrillation (AF) is unknown. Here we
      report a reduction of ventricular heart rate in a patient with permanent AF
      undergoing RDN. Subsequently, we investigated the effect of RDN on AF-induced
      shortening of atrial effective refractory period, AF inducibility, and
      ventricular rate control during AF maintained by rapid atrial pacing in 12 pigs
      undergoing RDN (n=7) or sham procedure (n=5). During sinus rhythm, RDN reduced
      heart rate (RR-interval, 708+/-12 versus 577+/-19 ms; P=0.0021) and increased
      atrioventricular node conduction time (PQ-interval, 112+/-12 versus 88+/-9 ms;
      P=0.0001). Atrial tachypacing for 30 minutes increased AF inducibility and
      decreased AF cycle length. This was not influenced by RDN. RDN reduced
      ventricular rate during AF episodes by ~24% (119+/-9 versus 158+/-19 bpm;
      P=0.0001). AF episodes were shorter after RDN compared with sham (12+/-3 versus
      34+/-4 s; P=0.0091), but atrial effective refractory period was not modified by
      RDN. RDN reduced heart rate and reduced atrioventricular node conduction time
      during sinus rhythm and provided rate control during AF. AF-induced atrial
      electrical remodeling, AF inducibility, and AF cycle length were not modified,
      but duration of AF episodes was shorter after RDN. Modulation of the autonomic
      nervous system by RDN might provide rate control and reduce susceptibility to AF.
      Whether RDN may provide rate control in a larger number of patients with AF
      deserves further clinical studies.

PMID- 23150503
TI  - Does dairy food intake predict arterial stiffness and blood pressure in men?:
      Evidence from the Caerphilly Prospective Study.
AB  - Arterial stiffness is an independent predictor of cardiovascular disease events
      and mortality, and like blood pressure, may be influenced by dairy food intake.
      Few studies have investigated the effects of consumption of these foods on
      prospective measures of arterial stiffness. The present analysis aimed to
      investigate the prospective relationship between milk, cheese, cream, and butter
      consumption and aortic pulse wave velocity, augmentation index, systolic and
      diastolic blood pressure, as well as cross-sectional relationships between these
      foods and systolic and diastolic blood pressure and metabolic markers using data
      from the Caerphilly Prospective Study. Included in this cohort were 2512 men,
      aged 45 to 59 years, who were followed up at 5-year intervals for a mean of 22.8
      years (number follow-up 787). Augmentation index was 1.8% lower in subjects in
      the highest quartiles of dairy product intake compared with the lowest (P
      trend=0.021), whereas in the highest group of milk consumption systolic blood
      pressure was 10.4 mm Hg lower (P trend=0.033) than in nonmilk consumers after a
      22.8-year follow-up. Cross-sectional analyses indicated that across increasing
      quartiles of butter intake, insulin (P trend=0.011), triacylglycerol (P
      trend=0.023), total cholesterol (P trend=0.002), and diastolic blood pressure (P
      trend=0.027) were higher. Across increasing groups of milk intake and quartiles
      of dairy product intake, glucose (P trend=0.032) and triglyceride concentrations
      (P trend=0.031) were lower, respectively. The present results confirm that
      consumption of milk predicts prospective blood pressure, whereas dairy product
      consumption, excluding butter, is not detrimental to arterial stiffness and
      metabolic markers. Further research is needed to better understand the mechanisms
      that underpin these relationships.

PMID- 23150502
TI  - Addition of highly sensitive troponin T and N-terminal pro-B-type natriuretic
      peptide to electrocardiography for detection of left ventricular hypertrophy:
      results from the Dallas Heart Study.
AB  - Left ventricular hypertrophy (LVH) is an independent, modifiable risk factor for
      cardiovascular disease. However, current screening strategies are limited. In
      2478 participants without clinical disease from the Dallas Heart Study, we
      evaluated a multimarker screening strategy that complements electrocardiographic
      (ECG) criteria for LVH with 2 biomarkers, amino-terminal pro-B-type natriuretic
      peptide and highly sensitive cardiac troponin T. An integer LVH risk score from 0
      to 3 was determined as the sum of the following: (1) LVH by Sokolow-Lyon ECG; (2)
      amino-terminal pro-B-type natriuretic peptide in the highest sex-specific
      quartile; and (3) detectable cardiac troponin T. Cardiac magnetic resonance
      imaging-determined LVH served as the primary outcome. The probability of LVH
      increased from 2% with an LVH risk score of 0 to 50% with a score of 3 (P<0.001).
      Sokolow-Lyon ECG afforded low sensitivity (26% [95% confidence interval {CI}, 17
      32%]) and high specificity (96% [95% CI, 95-97%]), whereas a risk score >=2
      offered higher sensitivity (44% [95% CI, 34-51%]) with good specificity (90% [95%
      CI, 89-93%]) and a score threshold of 1 offered reasonable sensitivity (76% [95%
      CI, 67-83%]) with lower specificity (55% [95% CI, 53-61%]) and high negative
      predictive value (98% [95% CI, 97-98%]). Area under the receiver operator
      characteristic curve improved from 0.760 (95% CI, 0.716-0.804) for ECG alone to
      0.798 (95% CI, 0.754-0.842) for the LVH risk score (P=0.0012), consistent with
      modest improvement in overall discrimination. Better screening for LVH may be
      achieved by combining simple tests, which collectively provide additional
      information compared with ECG alone. Further studies are needed to evaluate the
      impact and cost-effectiveness of a multimarker screening strategy.

PMID- 23150504
TI  - Functional regulation of ClC-3 in the migration of vascular smooth muscle cells.
AB  - Migration of vascular smooth muscle cells (VSMCs) into neointima contributes to
      atherosclerosis and restenosis. This migration requires coordinated plasmalemmal
      fluxes of water and ions. Here, we show that aortic VSMC migration depends on the
      regulation of transmembrane Cl(-) flux by ClC-3, a Cl(-) channel/transporter. The
      contribution of ClC-3 to plasmalemmal Cl(-) current was studied in VSMCs by
      electrophysiological recordings. Cl(-) current was negligible in cells perfused
      with 0 [Ca(2+)]. Raising intracellular [Ca(2+)] to 0.5 MUM activated a Cl(-)
      current (I(Cl.Ca)), approximately half of which was eliminated on inhibition by
      KN-93 of calmodulin-dependent protein kinase II. I(Cl.Ca) was also halved by
      inositol-3,4,5,6-tetrakisphosphate, a cellular signal with the biological
      function of specifically preventing calmodulin-dependent protein kinase II from
      activating I(Cl.Ca). Gene disruption of ClC-3 reduced I(Cl.Ca) by 50%. Moreover,
      I(Cl.Ca) in the ClC-3 null VSMCs was not affected by either KN-93 or inositol
      3,4,5,6-tetrakisphosphate. We conclude that I(Cl.Ca) is composed of 2 components,
      one is ClC-3 independent whereas the other is ClC-3 dependent, activated by
      calmodulin-dependent protein kinase II and inhibited by inositol-3,4,5,6
      tetrakisphosphate. We also assayed VSMC migration in transwell assays. Migration
      was halved in ClC-3 null cells versus wild-type cells. In addition, inhibition of
      ClC-3 by niflumic acid, KN-93, or inositol-3,4,5,6-tetrakisphosphate each reduced
      cell migration in wild-type cells but not in ClC-3 null cells. These cell
      signaling roles of ClC-3 in VSMC migration suggest new therapeutic approaches to
      vascular remodeling diseases.

PMID- 23150505
TI  - Common polymorphisms in the CYP11B1 and CYP11B2 genes: evidence for a digenic
      influence on hypertension.
AB  - The locus encompassing the corticosteroidogenic genes CYP11B2 and CYP11B1 is of
      potential importance in essential hypertension. We analyzed the association of
      polymorphisms at this locus with risk of essential hypertension, using 2 white
      case-control collections for discovery (n=3340) and confirmation (n=2929). Single
      marker and haplotype analyses were performed, with the CYP11B2 Intron 2
      Conversion polymorphism showing strongest association with hypertension in both
      cohorts and in combined analysis (odds ratio=1.16, P=8.54*10(-5)). The CYP11B1
      ACA haplotype associated with increased risk of hypertension relative to the
      alternative, GTC (odds ratio=1.11; P=7.4*10(-3)), whereas the CYP11B2 TWtC
      haplotype seemed protective relative to the contrasting CConvT (odds ratio=0.88,
      P=2.2*10(-3)). Analysis spanning the whole CYP11B1/CYP11B2 locus showed that
      haplotypes associated with raised risk of hypertension tend to coexist.
      Functional analysis of heterozygous human adrenal tissue demonstrated decreased
      CYP11B2 expression and increased CYP11B1 expression for those alleles associating
      with reduced risk of hypertension. These results confirm the hypertensive
      influence of this locus, with data suggesting a complex digenic mechanism whereby
      altered relative CYP11B1 and CYP11B2 gene expression could have a chronic effect
      on enzyme activity and corticosteroid synthesis.

PMID- 23150506
TI  - A role for TRPV1 in influencing the onset of cardiovascular disease in obesity.
AB  - Obesity induced by Western diets is associated with type 2 diabetes mellitus and
      cardiovascular diseases, although underlying mechanisms are unclear. We
      investigated a murine model of diet-induced obesity to determine the effect of
      transient potential receptor vanilloid 1 (TRPV1) deletion on hypertension and
      metabolic syndrome. Wild-type and TRPV1 knockout mice were fed normal or high-fat
      diet from 3 to 15 weeks. High-fat diet-fed mice from both genotypes became obese,
      with similar increases in body and adipose tissue weights. High-fat diet-fed
      TRPV1 knockout mice showed significantly improved handling of glucose compared
      with high-fat diet-fed wild-type mice. Hypertension, vascular hypertrophy, and
      altered nociception were observed in high-fat diet-fed wild-type but not high-fat
      diet-fed TRPV1 knockout mice. Wild-type, but not high-fat diet-fed TRPV1
      knockout, mice demonstrated remodeling in terms of aortic vascular hypertrophy
      and increased heart and kidney weight, although resistance vessel responses were
      similar in each. Moreover, the wild-type mice had significantly increased plasma
      levels of leptin, interleukin 10 and interleukin 1beta, whereas samples from
      TRPV1 knockout mice did not show significant increases. Our results do not
      support the concept that TRPV1 plays a major role in influencing weight gain.
      However, we identified a role of TRPV1 in the deleterious effects observed with
      high-fat feeding in terms of inducing hypertension, impairing thermal nociception
      sensitivity, and reducing glucose tolerance. The observation of raised levels of
      adipokines in wild-type but not TRPV1 knockout mice is in keeping with TRPV1
      involvement in stimulating the proinflammatory network that is central to obesity
      induced hypertension and sensory neuronal dysfunction.

PMID- 23150507
TI  - Physical activity and blood pressure in primary school children: a longitudinal
      study.
AB  - High blood pressure (BP) is becoming increasingly common during childhood.
      Regular physical activity (PA) reduces BP in adults, but limited studies have
      reported inconsistent results among children. The aim of this study is to
      examine, for the first time, the cross-sectional and longitudinal associations
      between BP and objectively measured PA in young children of predominantly South
      Asian background. Data from the Birmingham healthy Eating and Active lifestyle
      for CHildren Study were analyzed. Five hundred seventy-four children, aged 5 to 7
      years, underwent a series of measures at baseline and were followed up 2 years
      later. PA was objectively measured using accelerometry and converted to counts
      per minute (total PA, cpm), and time spent in moderate-vigorous PA (minutes per
      day). BP was measured by trained staff using standard protocols. Data were
      available for 512 children at baseline (mean age 6.5 years, range 5.4-7.8 years),
      and 427 of these children were followed up. Baseline total PA was inversely
      associated with diastolic BP at both baseline (adjusted regression coefficient: 
      0.75 mm Hg [95% CI -1.33 to -0.18] per 20 cpm) and follow-up (-0.74 mm Hg [95% CI
      -1.40 to -0.08]). All associations remained unchanged after further adjustment
      for weight status. This study strengthens evidence of a causal association
      between higher PA and lower BP in children as young as 5, independent of weight
      status. The results provide support for development of interventions to increase
      PA in young children.

PMID- 23150508
TI  - Thromboxane receptors in smooth muscle promote hypertension, vascular remodeling,
      and sudden death.
AB  - The prostanoid thromboxane A2 has been implicated to contribute to the
      pathogenesis of many cardiovascular diseases, including hypertension. To study
      the role of vascular thromboxane-prostanoid (TP) receptors in blood pressure
      regulation, we generated mice with cell-specific deletion of TP receptors in
      smooth muscle using Cre/Loxp technology. We crossed the KISM22alpha-Cre
      transgenic mouse line expressing Cre recombinase in smooth muscle cells with a
      mouse line bearing a conditional allele of the Tbxa2r gene (Tp(flox)). In
      KISM22alpha-Cre(+)Tp(flox/flox) (TP-SMKO) mice, TP receptors were efficiently
      deleted from vascular smooth muscle cells. In TP-SMKOs, acute vasoconstrictor
      responses to the TP agonist U46619 were attenuated to a similar extent in both
      the peripheral and renal circulations. Yet, acute vascular responses to
      angiotensin II were unaffected at baseline and after chronic angiotensin II
      administration. Infusion of high-dose U46619 caused circulatory collapse and
      death in a majority of control mice but had negligible hemodynamic effects in TP
      SMKOs, which were completely protected from U46619-induced sudden death. Baseline
      blood pressures were normal in TP-SMKOs. However, the absence of TP receptors in
      vascular smooth muscle cells was associated with significant attenuation of
      angiotensin II-induced hypertension and diminished vascular remodeling. This was
      also associated with reduced urinary thromboxane production after chronic
      angiotensin II. Thus, TP receptors in vascular smooth muscle cells play a major
      role in mediating the actions of thromboxane A(2) in TP agonist-induced shock,
      hypertension, and vascular remodeling of the aorta.

PMID- 23150509
TI  - Prenatal programming of hypertension: role of sympathetic response to physical
      stress.

PMID- 23150510
TI  - Higher ambulatory blood pressure is associated with aortic valve calcification in
      the elderly: a population-based study.
AB  - Aortic valve calcification (AVC) without outflow obstruction (stenosis) is common
      in the elderly and increases the risk of cardiovascular morbidity and mortality.
      Although high blood pressure (BP) measured at the doctor's office is known to be
      associated with AVC, little is known about the association between 24-hour
      ambulatory BP (ABP) and AVC. Our objective was to clarify the association between
      ABP variables and AVC. The study population consisted of 737 patients (mean age,
      71+/-9 years) participating in the Cardiovascular Abnormalities and Brain Lesions
      study who underwent 24-hour ABP monitoring. Each aortic valve leaflet was graded
      on a scale of 0 (normal) to 3 (severe calcification). A total valve score (values
      0-9) was calculated as the sum of all leaflet scores. Advanced AVC (score >=4)
      was present in 77 subjects (10.4%). All of the systolic ABP variables (except
      systolic BP nocturnal decline) and mean asleep diastolic BP were positively
      associated with advanced calcification, whereas normal dipping status and
      diastolic BP nocturnal decline were negatively associated. Multiple regression
      analysis indicated that mean awake diastolic BP (odds ratio, 1.31 [95% CI, 1.01
      1.71]) and asleep diastolic BP (odds ratio, 1.34 [95% CI, 1.04-1.72]) remained
      independently associated with advanced calcification after adjustment for age,
      sex, cigarette smoking, diabetes mellitus, hypercholesterolemia, hypertension,
      serum creatinine, and any degree of aortic insufficiency. Diastolic ABP is
      independently associated with advanced calcification. This finding may have
      important implications in gaining further insight into the mechanism of AVC.

PMID- 23150512
TI  - Morning surge, dipping, and sleep-time blood pressure as prognostic markers of
      cardiovascular risk.

PMID- 23150511
TI  - Carotid arterial stiffness and its relationship to exercise intolerance in older
      patients with heart failure and preserved ejection fraction.
AB  - Heart failure with a preserved ejection fraction (HFpEF) is the dominant form of
      heart failure in the older population. The primary chronic symptom in HFpEF is
      severe exercise intolerance; however, its pathophysiology and therapy are not
      well understood. We tested the hypothesis that older patients with HFpEF have
      increased arterial stiffness beyond what occurs with normal aging and that this
      contributes to their severe exercise intolerance. Sixty-nine patients >=60 years
      of age with HFpEF and 62 healthy volunteers (24 young healthy subjects <=30 years
      and 38 older healthy subjects >=60 years old) were examined. Carotid arterial
      stiffness was assessed using high-resolution ultrasound, and peak exercise oxygen
      consumption was measured using expired gas analysis. Peak exercise oxygen
      consumption was severely reduced in the HFpEF patients compared with older
      healthy subjects (14.1+/-2.9 versus 19.7+/-3.7 mL/kg per minute; P<0.001) and in
      both was reduced compared with young healthy subjects (32.0+/-7.2 mL/kg per
      minute; both P<0.001). In HFpEF compared with older healthy subjects, carotid
      arterial distensibility was reduced (0.97+/-0.45 versus 1.33+/-0.55*10(-3) mm Hg(
      1); P=0.008) and Young's elastic modulus was increased (1320+/-884 versus 925+/
      530 kPa; P<0.02). Carotid arterial distensibility was directly (0.28; P=0.02) and
      Young's elastic modulus was inversely (-0.32; P=0.01) related to peak exercise
      oxygen consumption. Carotid arterial distensibility is decreased in HFpEF beyond
      the changes attributed to normal aging and is related to peak exercise oxygen
      consumption. This supports the hypothesis that increased arterial stiffness
      contributes to exercise intolerance in HFpEF and is a potential therapeutic
      target.

PMID- 23150513
TI  - Endothelial NO synthase augments fetoplacental blood flow, placental
      vascularization, and fetal growth in mice.
AB  - It is not known whether eNOS deficiency in the mother or the conceptus (ie,
      placenta and fetus) causes fetal growth restriction in mice lacking the
      endothelial NO synthase gene (eNOS knockout [KO]). We hypothesized that eNOS
      sustains fetal growth by maintaining low fetoplacental vascular tone and
      promoting fetoplacental vascularity and that this is a conceptus effect and is
      independent of maternal genotype. We found that eNOS deficiency blunted fetal
      growth, and blunted the normal increase in umbilical blood flow and umbilical
      venous diameter and the decrease in umbilical arterial Resistance Index in late
      gestation (14.5-17.5 days) in eNOS KO relative to C57Bl/6J controls. On day 17.5,
      fetoplacental capillary lobule length and capillary density in vascular corrosion
      casts were reduced in eNOS KO placentas. Reduced vascularization may be a result
      of decreased vascular endothelial growth factor mRNA and protein expression in
      eNOS KO placentas at this stage. These factors, combined with significant anemia
      found in eNOS KO fetuses, would be anticipated to reduce fetal oxygen delivery
      and contribute to the fetal tissue hypoxia that was detected in the heart, lung,
      kidney, and liver by immunohistochemistry using pimonidazole. Although maternal
      eNOS deficiency impairs uteroplacental adaptations to pregnancy, maternal
      genotype was not a significant factor affecting growth in heterozygous
      conceptuses. This indicates that fetal growth restriction was primarily caused by
      conceptus eNOS deficiency. In mice, placental hemodynamic and vascular changes
      with gestation and growth restriction showed strong parallels with human
      pregnancy. Thus, the eNOS KO model could provide insights into the pathogenesis
      of human intrauterine growth restriction.

PMID- 23150514
TI  - Prenatal programming of hypertension induces sympathetic overactivity in response
      to physical stress.
AB  - Small-for-gestational-age infants are known to develop hypertension in adulthood.
      This prenatal programming of hypertension (PPH) can result from several insults
      including maternal dietary protein deprivation, uteroplacental insufficiency, and
      prenatal administration of glucocorticoids. The mechanisms underlying the
      development of hypertension remain unclear although the sympathetic nervous
      system has been indirectly implicated. This study was designed to directly
      measure renal sympathetic nerve activity both at rest and during physical stress
      in an animal model of PPH. The adult male offspring of rats fed either a 6% (PPH)
      or 20% protein diet (control) were investigated. Conscious systolic blood
      pressure measured by tail cuff was significantly higher in PPH compared with
      control (140 +/- 3 versus 128 +/- 3 mm Hg; P<0.05). Baseline mean arterial
      pressure, heart rate, and renal sympathetic activity were not different between
      groups during isoflurane anesthesia or after decerebration. Physical stress was
      induced in decerebrate animals by activating the exercise pressor reflex during
      static muscle contraction. Stimulation of the exercise pressor reflex evoked
      significantly larger changes from baseline in mean arterial pressure (40 +/- 7
      versus 20 +/- 4 mm Hg; P<0.05), heart rate (19 +/- 3 versus 5 +/- 1 bpm; P<0.05),
      and renal sympathetic activity (198 +/- 29% versus 68 +/- 14%; P<0.05) in PPH as
      compared with control. The data demonstrate that the sympathetic response to
      physical stress is markedly exaggerated in PPH and may play a significant role in
      the development of hypertension in adults born small for gestational age.

PMID- 23150516
TI  - Genomic association analysis identifies multiple loci influencing
      antihypertensive response to an angiotensin II receptor blocker.

PMID- 23150515
TI  - Influence of lower body positive pressure on upper airway cross-sectional area in
      drug-resistant hypertension.
AB  - We previously showed that in hypertensive patients the amount of fluid displaced
      from the legs overnight is directly related to the severity of obstructive sleep
      apnea and that the rostral fluid shift was greater in drug-resistant hypertensive
      patients. The findings suggested that this fluid redistribution increases upper
      airway collapsibility, yet more direct evidence is lacking. The present study
      examines the effects of graded lower body positive pressure on leg fluid volume,
      upper airway cross-sectional area, and neck circumference in patients with drug
      resistant hypertension (n=25) and controlled hypertension (n=15). In both groups,
      the reduction in mean upper airway cross-sectional area and oropharyngeal
      junction area, assessed by acoustic pharyngometry, and the increase in neck
      circumference, determined by mercury strain gauge plethysmography, were related
      to the amount of fluid displaced from the legs (R(2)=0.41, P<0.0001; R(2)=0.42,
      P<0.0001; and R(2)=0.47, P<0.0001, respectively). Displacement of leg fluid
      volume was significantly greater in patients with drug-resistant hypertension
      than in controlled hypertension (P<0.0001), and as a consequence, the former
      experienced greater reductions in mean upper airway cross-sectional area and
      oropharyngeal junction area (P=0.001 and P<0.0001, respectively). The findings
      support the concept that in hypertensive subjects, rostral fluid displacement may
      participate in the pathogenesis of obstructive sleep apnea by narrowing the upper
      airway and making it more susceptible to collapse during sleep. The exaggerated
      fluid volume displacement from the legs and upper airway response to lower body
      positive pressure in patients with drug-resistant hypertension provide additional
      evidence of an important link between drug-resistant hypertension and obstructive
      sleep apnea.

PMID- 23150517
TI  - Effect of SR manipulation on conduit artery dilation in humans.
AB  - The impact of manipulating shear stress on conduit artery vasodilation has not
      been comprehensively described in vivo. We hypothesized that manipulation of SR
      through the brachial and radial arteries would be associated with corresponding
      changes in diameter. We performed a series of studies involving the following:
      (1) leg cycle exercise at increasing intensities (~70 and 85% maximum heart rate
      [HRmax]) with simultaneous bilateral measurement of SR in the radial arteries;
      (2) leg cycle exercise for 30 minutes at 80% HRmax with simultaneous bilateral
      measurement of velocity and diameter in the brachial arteries; and (3) bilateral
      forearm heating for 30 minutes with simultaneous bilateral measurement of
      brachial artery diameter and blood velocity. Cycling and forearm heating
      interventions were performed in the presence of unilateral cuff inflation
      throughout the experiment, or starting during the intervention (15 minutes), to
      manipulate SR responses. Cuff placement was associated with lower radial artery
      SR responses (cuffed versus uncuffed, 248+/-49 versus 349+/-105 L/s 85% HRmax;
      P<0.01), and diameter responses were similarly attenuated (2.45+/-0.30 versus
      2.78+/-0.20 mm 85% HRmax; P<0.05). Exercise performed at 80% HRmax in the
      presence of unilateral cuff inflation also reduced brachial artery SR (cuffed
      versus uncuffed; 258+/-107 versus 454+/-157 L/s; P<0.01) and diameter (3.96+/
      0.39 versus 4.20+/-0.45 mm). Finally, cuff inflation decreased the impact of
      forearm heating on brachial SR (cuffed versus uncuffed; 262+/-97 versus 440+/-106
      L/s; P<0.01) and diameter (4.35+/-0.54 versus 4.87+/-0.47 mm; P<0.05). Similar
      significant differences between the cuffed and uncuffed limbs in SR and diameter
      were observed when cuff inflation occurred during exercise or heating. Our
      findings strongly implicate SR as an important stimulus to increase conduit
      artery diameter in humans.

PMID- 23150518
TI  - Pulsatile hemodynamics and microcirculation: evidence for a close relationship in
      hypertensive patients.
AB  - The possible relationships between indicators of small resistance artery
      structure and of arterial stiffness and central hemodynamics have not yet been
      evaluated. Aim of this study was to assess the relationship between indicators of
      large arteries stiffness, including carotido-femoral pulse wave velocity and of
      vascular alterations in small resistance arteries (media/lumen ratio, M/L) in
      patients with primary and secondary hypertension. In 73 patients (mean age, 53+/
      14 years, 34 females, 25 with type 2 diabetes mellitus, 18 never treated) with
      essential (n=37) and secondary (n=36) hypertension, carotido-femoral pulse wave
      velocity was measured. In all patients, small resistance arteries were dissected
      from subcutaneous fat biopsies and mounted on an isometric myograph, for the
      measurement of the M/L. Pulse wave analysis was performed in 67 patients. M/L
      ratio was significantly related to brachial systolic blood pressure and pulse
      pressure (r=0.36 and 0.31, P<0.001, respectively) and to central systolic and
      pulse pressure (r=0.44 and 0.42, P<0.001, respectively). A positive correlation
      was observed between M/L ratio and carotido-femoral pulse wave velocity (r=0.45;
      P<0.001); this correlation remained statistically significant after adjustment
      for age and mean blood pressure. M/L ratio was also associated to aortic
      augmentation index (r=0.33; P=0.008), and this correlations remained
      statistically significant after adjustment for potential confounders. In
      hypertensive patients, the presence of structural alterations of small resistance
      arteries may be associated with the increase in large arteries stiffness and
      possibly contribute to an increase in central pressure by increasing the
      magnitude of wave reflections.

PMID- 23150519
TI  - Lack of specificity of commercial antibodies leads to misidentification of
      angiotensin type 1 receptor protein.
AB  - The angiotensin II type 1 receptor (AT(1)R) mediates most hypertensive actions of
      angiotensin II. To understand the molecular regulation of the AT(1)R in normal
      physiology and pathophysiology, methods for sensitive and specific detection of
      AT(1)R protein are required. Here, we examined the specificity of a panel of
      putative AT(1)R antibodies that are commonly used by investigators in the field.
      For these studies, we carried out Western blotting and immunohistochemistry with
      kidney tissue from wild-type mice and genetically modified mice lacking the major
      murine AT(1)R isoform, AT(1A) (AT(1A)KO), or with combined deficiency of both the
      AT(1A) and AT(1B) isoforms (AT(1AB)KO). For the 3 antibodies tested, Western
      blots of protein homogenates from wild-type kidneys yielded distinct bands with
      the expected size range for AT(1)R. In addition, these bands appeared identical
      in samples from mice lacking 1 or both murine AT(1)R isoforms. Additionally, the
      pattern of immunohistochemical staining in kidneys, liver, and adrenal glands of
      wild-type mice was very similar to that of AT(1AB)KO mice completely lacking all
      AT(1)R. We verified the absence of AT(1)R subtypes in each mouse line by the
      following: (1) quantitative polymerase chain reaction documenting the absence of
      mRNA species, and (2) functionally by assessing angiotensin II-dependent
      vasoconstriction, which was substantially blunted in both AT(1A)KOs and
      AT(1AB)KOs. Finally, these antibodies failed to detect epitope-tagged AT(1A)R
      protein overexpressed in human embryonic kidney cells. We conclude that anti
      AT(1)R antibodies available from commercial sources and commonly used in
      published studies exhibit nonspecific binding in mouse tissue that may lead to
      erroneous results.

PMID- 23150520
TI  - Tissue-specific oxidative stress and loss of mitochondria in CoQ-deficient Pdss2
      mutant mice.
AB  - Primary human CoQ(10) deficiencies are clinically heterogeneous diseases caused
      by mutations in PDSS2 and other genes required for CoQ(10) biosynthesis. Our in
      vitro studies of PDSS2 mutant fibroblasts, with <20% CoQ(10) of control cells,
      revealed reduced activity of CoQ(10)-dependent complex II+III and ATP synthesis,
      without amplification of reactive oxygen species (ROS), markers of oxidative
      damage, or antioxidant defenses. In contrast, COQ2 and ADCK3 mutant fibroblasts,
      with 30-50% CoQ(10) of controls, showed milder bioenergetic defects but
      significantly increased ROS and oxidation of lipids and proteins. We hypothesized
      that absence of oxidative stress markers and cell death in PDSS2 mutant
      fibroblasts were due to the extreme severity of CoQ(10) deficiency. Here, we have
      investigated in vivo effects of Pdss2 deficiency in affected and unaffected
      organs of CBA/Pdss2(kd/kd) mice at presymptomatic, phenotypic-onset, and end
      stages of the disease. Although Pdss2 mutant mice manifest widespread CoQ(9)
      deficiency and mitochondrial respiratory chain abnormalities, only affected
      organs show increased ROS production, oxidative stress, mitochondrial DNA
      depletion, and reduced citrate synthase activity, an index of mitochondrial mass.
      Our data indicate that kidney-specific loss of mitochondria triggered by
      oxidative stress may be the cause of renal failure in Pdss2(kd/kd) mice.

PMID- 23150522
TI  - Generation of Rag1-knockout immunodeficient rats and mice using engineered
      meganucleases.
AB  - Despite the recent availability of gene-specific nucleases, such as zinc-finger
      nucleases (ZFNs) and transcription activator-like nucleases (TALENs), there is
      still a need for new tools to modify the genome of different species in an
      efficient, rapid, and less costly manner. One aim of this study was to apply, for
      the first time, engineered meganucleases to mutate an endogenous gene in animal
      zygotes. The second aim was to target the mouse and rat recombination activating
      gene 1 (Rag1) to describe, for the first time, Rag1 knockout immunodeficient
      rats. We microinjected a plasmid encoding a meganuclease for Rag1 into the
      pronucleus of mouse and rat zygotes. Mutant animals were detected by PCR
      sequencing of the targeted sequence. A homozygous RAG1-deficient rat line was
      generated and immunophenotyped. Meganucleases were efficient, because 3.4 and
      0.6% of mouse and rat microinjected zygotes, respectively, generated mutated
      animals. RAG1-deficient rats showed significantly decreased proportions and
      numbers of immature and mature T and B lymphocytes and normal NK cells vs.
      littermate wild-type controls. In summary, we describe the use of engineered
      meganucleases to inactivate an endogenous gene with efficiencies comparable to
      those of ZFNs and TALENs. Moreover, we generated an immunodeficient rat line
      useful for studies in which there is a need for biological parameters to be
      analyzed in the absence of immune responses.

PMID- 23150521
TI  - MRI reveals differential effects of amphetamine exposure on neuroglia in vivo.
AB  - How amphetamine affects the neuroglia in living brains is not well understood. In
      an effort to elucidate this effect, we investigated neuroglia in response to
      amphetamine exposure using antisense (AS) or sense (S) phosphorothioate-modified
      oligodeoxynucleotide (sODN) sequences that correspond to glial fibrillary acidic
      protein (GFAP) mRNA (AS-gfap or S-gfap, respectively) expression. The control is
      a random-sequence sODN (Ran). Using cyanine 5.5-superparamagnetic iron oxide
      nanoparticle (Cy5.5-SPION) labeling and fluorescent microscopy, we demonstrated
      that living neural progenitor cells (PC-12.1), as well as the cells in fresh
      brain slices and intact brains of male C57BL6 mice, exhibited universal uptake of
      all of the sODNs but rapidly excluded all sODN-Ran and most S-gfap. Moreover,
      transmission electron microscopy revealed electron-dense nanoparticles only in
      the neuroglia of normal or transgenic mice [B6;DBA-Tg(Fos-tTA, Fos
      EGFP*)1MmayTg(tetO-lacZ,tTA*)1Mmay/J] that had been administered AS-gfap or Cy5.5
      SPION-gfap. Subtraction R2* maps from mice with acute and chronic amphetamine
      exposure demonstrated, validated by postmortem immunohistochemistry, a reduction
      in striatal neuroglia, with gliogenesis in the subventricular zone and the
      somatosensory cortex in vivo. The sensitivity of our unique gene transcript
      targeted MRI was illustrated by a positive linear correlation (r(2)=1.0) between
      in vivo MRI signal changes and GFAP mRNA copy numbers determined by ex vivo
      quantitative RT-PCR. The study provides direct evidence for targeting neuroglia
      by antisense DNA-based SPION-gfap that enables in vivo MRI of inaccessible tissue
      with PCR sensitivity. The results enable us to conclude that amphetamine induces
      toxicity to neuroglia in vivo, which may cause remodeling or reconnectivity of
      neuroglia.

PMID- 23150523
TI  - Neurosteroid-mediated regulation of brain innate immunity in HIV/AIDS: DHEA-S
      suppresses neurovirulence.
AB  - Neurosteroids are cholesterol-derived molecules synthesized within the brain,
      which exert trophic and protective actions. Infection by human and feline
      immunodeficiency viruses (HIV and FIV, respectively) causes neuroinflammation and
      neurodegeneration, leading to neurological deficits. Secretion of
      neuroinflammatory host and viral factors by glia and infiltrating leukocytes
      mediates the principal neuropathogenic mechanisms during lentivirus infections,
      although the effect of neurosteroids on these processes is unknown. We
      investigated the interactions between neurosteroid-mediated effects and
      lentivirus infection outcomes. Analyses of HIV-infected (HIV(+)) and uninfected
      human brains disclosed a reduction in neurosteroid synthesis enzyme expression.
      Human neurons exposed to supernatants from HIV(+) macrophages exhibited
      suppressed enzyme expression without reduced cellular viability. HIV(+) human
      macrophages treated with sulfated dehydroepiandrosterone (DHEA-S) showed
      suppression of inflammatory gene (IL-1beta, IL-6, TNF-alpha) expression. FIV
      infected (FIV(+)) animals treated daily with 15 mg/kg body weight. DHEA-S
      treatment reduced inflammatory gene transcripts (IL-1beta, TNF-alpha, CD3epsilon,
      GFAP) in brain compared to vehicle-(beta-cyclodextrin)-treated FIV(+) animals
      similar to levels found in vehicle-treated FIV(-) animals. DHEA-S treatment also
      increased CD4(+) T-cell levels and prevented neurobehavioral deficits and
      neuronal loss among FIV(+) animals, compared to vehicle-treated FIV(+) animals.
      Reduced neuronal neurosteroid synthesis was evident in lentivirus infections, but
      treatment with DHEA-S limited neuroinflammation and prevented neurobehavioral
      deficits. Neurosteroid-derived therapies could be effective in the treatment of
      virus- or inflammation-mediated neurodegeneration.

PMID- 23150525
TI  - Regulation of co- and post-translational myristoylation of proteins during
      apoptosis: interplay of N-myristoyltransferases and caspases.
AB  - Myristoylation occurs cotranslationally on nascent proteins and post
      translationally during apoptosis after caspase cleavages expose cryptic
      myristoylation sites. We demonstrate a drastic change in the myristoylated
      protein proteome in apoptotic cells, likely as more substrates are revealed by
      caspases. We show for the first time that both N-myristoyltransferases (NMTs) 1
      and 2 are cleaved during apoptosis and that the caspase-3- or -8-mediated
      cleavage of NMT1 at Asp-72 precedes the cleavage of NMT2 by caspase-3 mainly at
      Asp-25. The cleavage of NMTs did not significantly affect their activity in
      apoptotic cells until the 8 h time point. However, the cleavage of the
      predominantly membrane bound NMT1 (64%) removed a polybasic domain stretch and
      led to a cytosolic relocalization (>55%), whereas predominantly cytosolic NMT2
      (62%) relocalized to membranes when cleaved (>80%) after the removal of a
      negatively charged domain. The interplay between caspases and NMTs during
      apoptosis is of particular interest since caspases may not only control the rates
      of substrate production but also their myristoylation rate by regulating the
      location and perhaps the specificity of NMTs. Since apoptosis is often suppressed
      in cancer, the reduced caspase activity seen in cancer cells might also explain
      the higher NMT levels observed in many cancers.

PMID- 23150524
TI  - Embryonic exposure to propylthiouracil disrupts left-right patterning in Xenopus
      embryos.
AB  - Antithyroid medications are the preferred therapy for the treatment of Graves'
      disease during pregnancy. Propylthiouracil (PTU) is favored over methimazole
      (MMI) due to potential teratogenic concerns with MMI. This study was to determine
      the teratogenic potential of MMI and PTU using a validated Xenopus tropicalis
      embryo model. Embryos were exposed to 1 mM PTU (EC(50)=0.88 mM), 1 mM MMI, or
      vehicle control (water) from stages 2 to 45. Treated embryos were examined for
      gross morphological defects, ciliary function, and gene expression by in situ
      hybridization. Exposure to PTU, but not MMI, led to cardiac and gut looping
      defects and shortening along the anterior-posterior axis. PTU exposure during
      gastrulation (stage 8-12.5) was identified as the critical period of exposure
      leading to left-right (LR) patterning defects. Abnormal cilia polarization,
      abnormal cilia-driven leftward flow at the gastrocoel roof plate (GRP), and
      aberrant expression of both Coco and Pitx2c were associated with abnormal LR
      symmetry observed following PTU exposure. PTU is teratogenic during late
      blastula, gastrulation, and neurulation; whereas MMI is not. PTU alters ciliary
      driven flow and disrupts the normal genetic program involved in LR axis
      determination. These studies have important implications for women taking PTU
      during early pregnancy.

PMID- 23150527
TI  - Relatives' experiences of frontal-variant frontotemporal dementia.
AB  - In this article we address how relatives of people with frontal-variant
      frontotemporal dementia (fvFTD) experience the illness and how it impacts their
      lives. We interviewed 6 participants and carried out interpretative
      phenomenological analysis. We report on 11 themes that reflect distinctive
      challenges. Five themes relate to witnessing bizarre and strange changes: changed
      appetites and drives, loss of planning ability, loss of inhibition leading to
      social embarrassment, risky behavior, and communication problems. Four relate to
      managing these changes and two to the impact on the person and his or her
      relationships. Relatives must live with unusual changes in the person with fvFTD
      and the stigma this carries in social settings. They learn to act assertively for
      their relatives and put effort into promoting quality of life, using strategies
      adapted for fvFTD. Relatives grieve the loss of the person with fvFTD and their
      mutual relationship, but nonetheless find sources of solace and hope.

PMID- 23150528
TI  - Transforming community members into diabetes cultural health brokers: the
      Neighborhood Health Talker project.
AB  - PURPOSE: The purpose of this study was to evaluate a community-based diabetes
      education pilot project. The Neighborhood Health Talker project aimed to train
      and implement cultural health brokers primarily targeting communities of color to
      improve community members' diabetes knowledge and diabetes self-management
      skills. A secondary aim was to establish diabetes resource libraries accessible
      to communities that normally experience barriers to these resources. METHODS:
      Recruited community members completed 1 week of formal training developed by a
      multidisciplinary team in Buffalo, NY. The effect of training was evaluated
      through the use of baseline surveys, a pretest/posttest covering all training
      content, and daily quizzes evaluating knowledge relevant to each of the five
      training modules. Trained NHTs then held at least five community conversations in
      various locations and administered anonymous postconversation surveys to
      participants. Descriptive statistics and qualitative analysis techniques were
      used to summarize test, quiz, and survey results. RESULTS: Twelve women and 1 man
      completed the training program. Working alone as well as in pairs, each held at
      least five community conversations reaching over 700 community members of all
      ages over 3 months and established 8 diabetes resource libraries in the
      community. All trainees increased their diabetes knowledge and confidence as well
      as their abilities to perform the tasks of a cultural health broker. Trainees
      also indicated that the goals they set at training initiation were met.
      CONCLUSIONS: The training was successful in increasing trainee knowledge and
      confidence about diabetes prevention and self-management. Participants not only
      developed proficiency in discussing diabetes, they also made important lifestyle
      changes that demonstrated their commitment to the cause and the project. Low-cost
      initiatives like this are easily reproducible in other communities of color and
      could be modified to meet the needs of other communities as well.

PMID- 23150529
TI  - The impact of point-of-care A1C testing on provider compliance and A1C levels in
      a primary setting.
AB  - PURPOSE: The purpose of the research was to investigate the impact of point-of
      care (POC) A1C testing among patients with type 2 diabetes in a primary care
      setting. METHODS: This study used a pretest-posttest design with data from
      patient charts matched for age, sex, race, body mass index, insurance status, and
      the number of comorbidities. A random sample of charts of patients with type 2
      diabetes in the primary care setting was reviewed 6 months and 3 months pre- and
      post-implementation of the POC A1C testing. RESULTS: There was a significant
      difference in the number of A1Cs documented in the medical record pre- versus
      post-implementation of POC A1C. There was also a significant difference in A1C
      values pre- versus post-implementation. There was also a difference in the
      treatment changes pre- versus post-implementation of POC A1C. CONCLUSION: Point
      of-care A1C testing represents an opportunity for improved care of people with
      diabetes. The significance of this improvement will become more critical as the
      number of people with type 2 diabetes continues to increase.

PMID- 23150526
TI  - Substrate specificity of Pasteurella multocida toxin for alpha subunits of
      heterotrimeric G proteins.
AB  - Pasteurella multocida is the causative agent of a number of epizootic and
      zoonotic diseases. Its major virulence factor associated with atrophic rhinitis
      in animals and dermonecrosis in bite wounds is P. multocida toxin (PMT). PMT
      stimulates signal transduction pathways downstream of heterotrimeric G proteins,
      leading to effects such as mitogenicity, blockade of apoptosis, or inhibition of
      osteoblast differentiation. On the basis of Galpha(i2), it was demonstrated that
      the toxin deamidates an essential glutamine residue of the Galpha(i2) subunit,
      leading to constitutive activation of the G protein. Here, we studied the
      specificity of PMT for its G-protein targets by mass spectrometric analyses and
      by utilizing a monoclonal antibody, which recognizes specifically G proteins
      deamidated by PMT. The studies revealed deamidation of 3 of 4 families of
      heterotrimeric G proteins (Galpha(q/11), Galpha(i1,2,3), and Galpha(12/13) of
      mouse or human origin) by PMT but not by a catalytic inactive toxin mutant. With
      the use of G-protein fragments and chimeras of responsive or unresponsive G
      proteins, the structural basis for the discrimination of heterotrimeric G
      proteins was studied. Our results elucidate substrate specificity of PMT on the
      molecular level and provide evidence for the underlying structural reasons of
      substrate discrimination.

PMID- 23150530
TI  - Readiness for living independently among emerging adults with type 1 diabetes.
AB  - PURPOSE: The purpose of the study was to examine the association of time (high
      school to post-high school), living situation (independent of parents or not),
      diabetes-specific self-efficacy, and worry about hypoglycemia and how diabetes
      specific self-efficacy and worry about hypoglycemia are associated with diabetes
      management among emerging adults with type 1 diabetes. METHODS: Participants (N =
      114) completed measures on diabetes management, diabetes-specific self-efficacy,
      and worry about hypoglycemia during the last 6 months in high school (T1) and
      diabetes management, diabetes-specific self-efficacy, and living situation post
      high school (T2). General linear mixed model for the diabetes management outcome
      was used to test associations with diabetes-specific self-efficacy, worry about
      hypoglycemia, time, and living situation independent variables. Moderation by
      diabetes-specific self-efficacy and worry about hypoglycemia was also tested.
      RESULTS: Diabetes management increased from high school to post-high school but
      was not significantly associated with living situation (independent of parents or
      not). Diabetes management was better for youth with greater diabetes-specific
      self-efficacy. However, neither diabetes-specific self-efficacy nor worry about
      hypoglycemia moderated the relationship between diabetes management and time or
      between diabetes management and living situation. CONCLUSIONS: Diabetes
      management improved over time for these emerging adults with type 1 diabetes.
      Diabetes-specific self-efficacy is important for diabetes management regardless
      of whether youth are in high school or post-high school and whether living with
      parents or not.

PMID- 23150531
TI  - Developing and piloting the Journey to Native Youth Health program in Northern
      Plains Indian communities.
AB  - PURPOSE: The purpose of this study was to develop a lifestyle change program for
      Native American youth by modifying the Diabetes Prevention Program (DPP) and
      assess implementation indicators and short term behavioral and physiological
      outcomes of the intervention among a small pilot sample. METHODS: Community
      members and project staff modified the original DPP to be developmentally and
      culturally appropriate for youth targeting healthy weight maintenance, lowering
      fat intake, and increasing physical activity. Modifications included
      incorporating cultural aspects and delivering the program in small groups led by
      community members. Sixty-four Native American youth, aged 10-14 years old were
      recruited from 2 Montana Indian reservations to participate in the project,
      titled "Journey to Native Youth Health." Participants were randomized to the
      Journey DPP or a health-oriented comparison condition. Pretest and posttest
      measures included body mass index (BMI), dietary intake, physical activity (PA),
      and nutrition knowledge, attitudes and beliefs (KAB). RESULTS: The target number
      of participants was recruited and 84% completed the program and final measures.
      Changes favoring the Journey DPP group were observed on measures of PA, KAB, and
      kilocalories from fat consumed. As expected given the short (3-month) duration of
      treatment, there was no overall effect on BMI at end of treatment. Among youth
      who were overweight or obese at baseline, however, the Journey DPP had lower BMI
      growth. CONCLUSIONS: Results suggest the Journey DPP is feasible to implement and
      has the potential to impact behaviors and weight gain associated with risk for
      type-2 diabetes in Native American youth.

PMID- 23150532
TI  - Traumatic brain injury, paraquat exposure, and their relationship to Parkinson
      disease.
AB  - OBJECTIVES: Traumatic brain injury (TBI) increased risk of Parkinson disease (PD)
      in many but not all epidemiologic studies, giving rise to speculations about
      modifying factors. A recent animal study suggested that the combination of TBI
      with subthreshold paraquat exposure increases dopaminergic neurodegeneration. The
      objective of our study was to investigate PD risk due to both TBI and paraquat
      exposure in humans. METHODS: From 2001 to 2011, we enrolled 357 incident
      idiopathic PD cases and 754 population controls in central California. Study
      participants were asked to report all head injuries with loss of consciousness
      for >5 minutes. Paraquat exposure was assessed via a validated geographic
      information system (GIS) based on records of pesticide applications to
      agricultural crops in California since 1974. This GIS tool assesses ambient
      pesticide exposure within 500 m of residences and workplaces. RESULTS: In
      logistic regression analyses, we observed a 2-fold increase in risk of PD for
      subjects who reported a TBI (adjusted odds ratio [AOR] 2.00, 95% confidence
      interval [CI] 1.28-3.14) and a weaker association for paraquat exposures (AOR
      1.36, 95% CI 1.02-1.81). However, the risk of developing PD was 3-fold higher
      (AOR 3.01, 95% CI 1.51-6.01) in study participants with a TBI and exposure to
      paraquat than those exposed to neither risk factor. CONCLUSIONS: While TBI and
      paraquat exposure each increase the risk of PD moderately, exposure to both
      factors almost tripled PD risk. These environmental factors seem to act together
      to increase PD risk in a more than additive manner.

PMID- 23150533
TI  - Parkinson disease and driving: an evidence-based review.
AB  - The growing literature on driving in Parkinson disease (PD) has shown that
      driving is impaired in PD compared to healthy comparison drivers. PD is a complex
      neurodegenerative disorder leading to motor, cognitive, and visual impairments,
      all of which can affect fitness to drive. In this review, we examined studies of
      driving performance (on-road tests and simulators) in PD for outcome measures and
      their predictors. We searched through various databases and found 25 (of 99)
      primary studies, all published in English. Using the American Academy of
      Neurology criteria, a study class of evidence was assigned (I-IV, I indicating
      the highest level of evidence) and recommendations were made (Level A: predictive
      or not; B: probably predictive or not; C: possibly predictive or not; U: no
      recommendations). From available Class II and III studies, we identified various
      cognitive, visual, and motor measures that met different levels of evidence
      (usually Level B or C) with respect to predicting on-road and simulated driving
      performance. Class I studies reporting Level A recommendations for definitive
      predictors of driving performance in drivers with PD are needed by policy makers
      and clinicians to develop evidence-based guidelines.

PMID- 23150534
TI  - Contrast-enhanced ultrasound and detection of carotid plaque neovascularization.
AB  - A 62-year-old man was admitted after recurrent transient left-sided weakness and
      sensory loss. Ultrasound (US) examination revealed a 70% narrowing of the right
      proximal internal carotid artery (ICA). Contrast-enhanced US suggested plaque
      neovascularization (figure, A). Carotid endarterectomy of the right ICA was
      performed. Immunohistochemistry of the specimen showed, corresponding to the US
      findings, extensive plaque neovascularization associated with dense macrophage
      infiltration (figure, B, C). Plaque neovascularization is associated with
      inflammation and plaque progression.(1) The detection of plaque
      neovascularization by contrast-enhanced US could give further evidence of plaque
      vulnerability, but further study is needed to determine its value.

PMID- 23150535
TI  - Emerging subspecialties in neurology: neuroimmunology.

PMID- 23150536
TI  - Teaching neuroimages: a case of tubercular arteritis and stroke after early
      discontinuation of antibiotic therapy.

PMID- 23150537
TI  - Teaching neuroimages:crossed cerebellar diaschisis in hemispheric status
      epilepticus.

PMID- 23150540
TI  - Quantitative single-cell characterization of bacterial interactions reveals type
      VI secretion is a double-edged sword.
AB  - Interbacterial interaction pathways play an important role in defining the
      structure and complexity of bacterial associations. A quantitative description of
      such pathways offers promise for understanding the forces that contribute to
      community composition. We developed time-lapse fluorescence microscopy methods
      for quantitation of interbacterial interactions and applied these to the
      characterization of type VI secretion (T6S) in Pseudomonas aeruginosa. Our
      analyses allowed a direct determination of the efficiency of recipient cell lysis
      catalyzed by this intercellular toxin delivery pathway and provided evidence that
      its arsenal extends beyond known effector proteins. Measurement of T6S apparatus
      localization revealed correlated activation among neighboring cells, which, taken
      together with genetic data, implicate the elaboration of a functional T6S
      apparatus with a marked increase in susceptibility to intoxication. This
      possibility was supported by the identification of T6S-inactivating mutations in
      a genome-wide screen for resistance to T6S-mediated intoxication and by time
      lapse fluorescence microscopy analyses showing a decreased lysis rate of
      recipient cells lacking T6S function. Our discoveries highlight the utility of
      single-cell approaches for measuring interbacterial phenomena and provide a
      foundation for studying the contribution of a widespread bacterial interaction
      pathway to community structure.

PMID- 23150538
TI  - Generalized reproduction numbers and the prediction of patterns in waterborne
      disease.
AB  - Understanding, predicting, and controlling outbreaks of waterborne diseases are
      crucial goals of public health policies, but pose challenging problems because
      infection patterns are influenced by spatial structure and temporal asynchrony.
      Although explicit spatial modeling is made possible by widespread data mapping of
      hydrology, transportation infrastructure, population distribution, and
      sanitation, the precise condition under which a waterborne disease epidemic can
      start in a spatially explicit setting is still lacking. Here we show that the
      requirement that all the local reproduction numbers R0 be larger than unity is
      neither necessary nor sufficient for outbreaks to occur when local settlements
      are connected by networks of primary and secondary infection mechanisms. To
      determine onset conditions, we derive general analytical expressions for a
      reproduction matrix G0, explicitly accounting for spatial distributions of human
      settlements and pathogen transmission via hydrological and human mobility
      networks. At disease onset, a generalized reproduction number Lambda0 (the
      dominant eigenvalue of G0) must be larger than unity. We also show that
      geographical outbreak patterns in complex environments are linked to the dominant
      eigenvector and to spectral properties of G0. Tests against data and computations
      for the 2010 Haiti and 2000 KwaZulu-Natal cholera outbreaks, as well as against
      computations for metapopulation networks, demonstrate that eigenvectors of G0
      provide a synthetic and effective tool for predicting the disease course in space
      and time. Networked connectivity models, describing the interplay between
      hydrology, epidemiology, and social behavior sustaining human mobility, thus
      prove to be key tools for emergency management of waterborne infections.

PMID- 23150539
TI  - Bacterial quorum sensing, cooperativity, and anticipation of stationary-phase
      stress.
AB  - Acyl-homoserine lactone-mediated quorum sensing (QS) regulates diverse activities
      in many species of Proteobacteria. QS-controlled genes commonly code for
      production of secreted or excreted public goods. The acyl-homoserine lactones are
      synthesized by members of the LuxI signal synthase family and are detected by
      cognate members of the LuxR family of transcriptional regulators. QS affords a
      means of population density-dependent gene regulation. Control of public goods
      via QS provides a fitness benefit. Another potential role for QS is to anticipate
      overcrowding. As population density increases and stationary phase approaches, QS
      might induce functions important for existence in stationary phase. Here we
      provide evidence that in three related species of the genus Burkholderia QS
      allows individuals to anticipate and survive stationary-phase stress. Survival
      requires QS-dependent activation of cellular enzymes required for production of
      excreted oxalate, which serves to counteract ammonia-mediated alkaline toxicity
      during stationary phase. Our findings provide an example of QS serving as a means
      to anticipate stationary phase or life at the carrying capacity of a population
      by activating the expression of cytoplasmic enzymes, altering cellular
      metabolism, and producing a shared resource or public good, oxalate.

PMID- 23150542
TI  - Implantable microenvironments to attract hematopoietic stem/cancer cells.
AB  - The environments that harbor hematopoietic stem and progenitor cells are critical
      to explore for a better understanding of hematopoiesis during health and disease.
      These compartments often are inaccessible for controlled and rapid
      experimentation, thus limiting studies to the evaluation of conventional cell
      culture and transgenic animal models. Here we describe the manufacture and image
      guided monitoring of an engineered microenvironment with user-defined properties
      that recruits hematopoietic progenitors into the implant. Using intravital
      imaging and fluorescence molecular tomography, we show in real time that the cell
      homing and retention process is efficient and durable for short- and long-term
      engraftment studies. Our results indicate that bone marrow stromal cells,
      precoated on the implant, accelerate the formation of new sinusoidal blood
      vessels with vascular integrity at the microcapillary level that enhances the
      recruitment hematopoietic progenitor cells to the site. This implantable
      construct can serve as a tool enabling the study of hematopoiesis.

PMID- 23150541
TI  - Reading and doing arithmetic nonconsciously.
AB  - The modal view in the cognitive and neural sciences holds that consciousness is
      necessary for abstract, symbolic, and rule-following computations. Hence,
      semantic processing of multiple-word expressions, and performing of abstract
      mathematical computations, are widely believed to require consciousness. We
      report a series of experiments in which we show that multiple-word verbal
      expressions can be processed outside conscious awareness and that multistep,
      effortful arithmetic equations can be solved unconsciously. All experiments used
      Continuous Flash Suppression to render stimuli invisible for relatively long
      durations (up to 2,000 ms). Where appropriate, unawareness was verified using
      both objective and subjective measures. The results show that novel word
      combinations, in the form of expressions that contain semantic violations, become
      conscious before expressions that do not contain semantic violations, that the
      more negative a verbal expression is, the more quickly it becomes conscious, and
      that subliminal arithmetic equations prime their results. These findings call for
      a significant update of our view of conscious and unconscious processes.

PMID- 23150543
TI  - Looking just below the eyes is optimal across face recognition tasks.
AB  - When viewing a human face, people often look toward the eyes. Maintaining good
      eye contact carries significant social value and allows for the extraction of
      information about gaze direction. When identifying faces, humans also look toward
      the eyes, but it is unclear whether this behavior is solely a byproduct of the
      socially important eye movement behavior or whether it has functional importance
      in basic perceptual tasks. Here, we propose that gaze behavior while determining
      a person's identity, emotional state, or gender can be explained as an adaptive
      brain strategy to learn eye movement plans that optimize performance in these
      evolutionarily important perceptual tasks. We show that humans move their eyes to
      locations that maximize perceptual performance determining the identity, gender,
      and emotional state of a face. These optimal fixation points, which differ
      moderately across tasks, are predicted correctly by a Bayesian ideal observer
      that integrates information optimally across the face but is constrained by the
      decrease in resolution and sensitivity from the fovea toward the visual periphery
      (foveated ideal observer). Neither a model that disregards the foveated nature of
      the visual system and makes fixations on the local region with maximal
      information, nor a model that makes center-of-gravity fixations correctly predict
      human eye movements. Extension of the foveated ideal observer framework to a
      large database of real-world faces shows that the optimality of these strategies
      generalizes across the population. These results suggest that the human visual
      system optimizes face recognition performance through guidance of eye movements
      not only toward but, more precisely, just below the eyes.

PMID- 23150544
TI  - Implantable, multifunctional, bioresorbable optics.
AB  - Advances in personalized medicine are symbiotic with the development of novel
      technologies for biomedical devices. We present an approach that combines
      enhanced imaging of malignancies, therapeutics, and feedback about therapeutics
      in a single implantable, biocompatible, and resorbable device. This confluence of
      form and function is accomplished by capitalizing on the unique properties of
      silk proteins as a mechanically robust, biocompatible, optically clear
      biomaterial matrix that can house, stabilize, and retain the function of
      therapeutic components. By developing a form of high-quality microstructured
      optical elements, improved imaging of malignancies and of treatment monitoring
      can be achieved. The results demonstrate a unique family of devices for in vitro
      and in vivo use that provide functional biomaterials with built-in optical signal
      and contrast enhancement, demonstrated here with simultaneous drug delivery and
      feedback about drug delivery with no adverse biological effects, all while slowly
      degrading to regenerate native tissue.

PMID- 23150545
TI  - Tissue-resident memory CD8+ T cells continuously patrol skin epithelia to quickly
      recognize local antigen.
AB  - Recent work has demonstrated that following the clearance of infection a stable
      population of memory T cells remains present in peripheral organs and contributes
      to the control of secondary infections. However, little is known about how tissue
      resident memory T cells behave in situ and how they encounter newly infected
      target cells. Here we demonstrate that antigen-specific CD8(+) T cells that
      remain in skin following herpes simplex virus infection show a steady-state
      crawling behavior in between keratinocytes. Spatially explicit simulations of the
      migration of these tissue-resident memory T cells indicate that the migratory
      dendritic behavior of these cells allows the detection of antigen-expressing
      target cells in physiologically relevant time frames of minutes to hours.
      Furthermore, we provide direct evidence for the identification of rare antigen
      expressing epithelial cells by skin-patrolling memory T cells in vivo. These data
      demonstrate the existence of skin patrol by memory T cells and reveal the value
      of this patrol in the rapid detection of renewed infections at a previously
      infected site.

PMID- 23150546
TI  - Gated rotation mechanism of site-specific recombination by phiC31 integrase.
AB  - Integrases, such as that of the Streptomyces temperate bacteriophage phiC31,
      promote site-specific recombination between DNA sequences in the bacteriophage
      and bacterial genomes to integrate or excise the phage DNA. phiC31 integrase
      belongs to the serine recombinase family, a large group of structurally related
      enzymes with diverse biological functions. It has been proposed that serine
      integrases use a "subunit rotation" mechanism to exchange DNA strands after
      double-strand DNA cleavage at the two recombining att sites, and that many rounds
      of subunit rotation can occur before the strands are religated. We have analyzed
      the mechanism of phiC31 integrase-mediated recombination in a topologically
      constrained experimental system using hybrid "phes" recombination sites, each of
      which comprises a phiC31 att site positioned adjacent to a regulatory sequence
      recognized by Tn3 resolvase. The topologies of reaction products from circular
      substrates containing two phes sites support a right-handed subunit rotation
      mechanism for catalysis of both integrative and excisive recombination. Strand
      exchange usually terminates after a single round of 180 degrees  rotation.
      However, multiple processive "360 degrees  rotation" rounds of strand exchange
      can be observed, if the recombining sites have nonidentical base pairs at their
      centers. We propose that a regulatory "gating" mechanism normally blocks multiple
      rounds of strand exchange and triggers product release after a single round.

PMID- 23150547
TI  - Estrogen dependent activation function of ERbeta is essential for the sexual
      behavior of mouse females.
AB  - We previously generated and characterized a genuine estrogen receptor (ER) beta
      null mouse line (named ERbeta(ST)(L-/L-)) and showed that ERbeta(ST)(L-/L-) mice
      were sterile, due to an ovulation impairment in females and to an unknown reason
      in males, as their reproductive organs and spermatozoid motility appeared normal.
      We report here an assessment of the sexual behavior of ERbeta(ST)(L-/L-) null
      mice. We found that ERbeta(ST)(L-/L-) males display mildly impaired sexual
      behavior and that ERbeta(ST)(L-/L-) females are significantly less receptive and
      less attractive than wild-type (WT) females. Decreased attractivity is also
      exhibited by ERbetaAF2(0) but not by ERbetaAF1(0) mutant females (females devoid
      of either AF2 or AF1 activation function of ERbeta). Interestingly, by using an
      odor preference test, we have determined that the low attractiveness of
      ERbeta(ST)(L-/L-) and ERbetaAF2(0) females is related to a deficiency of a
      volatile chemosignal.

PMID- 23150550
TI  - Neural basis of contagious itch and why some people are more prone to it.
AB  - Watching someone scratch himself can induce feelings of itchiness in the
      perceiver. This provides a unique opportunity to characterize the neural basis of
      subjective experiences of itch, independent of changes in peripheral inputs. In
      this study, we first established that the social contagion of itch is essentially
      a normative response (experienced by most people), and that the degree of
      contagion is related to trait differences in neuroticism (i.e., the tendency to
      experience negative emotions), but not to empathy. Watching video clips of
      someone scratching (relative to control videos of tapping) activated, as
      indicated by functional neuroimaging, many of the neural regions linked to the
      physical perception of itch, including anterior insular, primary somatosensory,
      and prefrontal (BA44) and premotor cortices. Moreover, activity in the left BA44,
      BA6, and primary somatosensory cortex was correlated with subjective ratings of
      itchiness, and the responsivity of the left BA44 reflected individual differences
      in neuroticism. Our findings highlight the central neural generation of the
      subjective experience of somatosensory perception in the absence of somatosensory
      stimulation. We speculate that the habitual activation of this central "itch
      matrix" may give rise to psychogenic itch disorders.

PMID- 23150548
TI  - Multimodal imaging of the self-regulating developing brain.
AB  - Self-regulation refers to the ability to control behavior, cognition, and
      emotions, and self-regulation failure is related to a range of neuropsychiatric
      problems. It is poorly understood how structural maturation of the brain brings
      about the gradual improvement in self-regulation during childhood. In a large
      scale multicenter effort, 735 children (4-21 y) underwent structural MRI for
      quantification of cortical thickness and surface area and diffusion tensor
      imaging for quantification of the quality of major fiber connections. Brain
      development was related to a standardized measure of cognitive control (the
      flanker task from the National Institutes of Health Toolbox), a critical
      component of self-regulation. Ability to inhibit responses and impose cognitive
      control increased rapidly during preteen years. Surface area of the anterior
      cingulate cortex accounted for a significant proportion of the variance in
      cognitive performance. This finding is intriguing, because characteristics of the
      anterior cingulum are shown to be related to impulse, attention, and executive
      problems in neurodevelopmental disorders, indicating a neural foundation for self
      regulation abilities along a continuum from normality to pathology. The
      relationship was strongest in the younger children. Properties of large-fiber
      connections added to the picture by explaining additional variance in cognitive
      control. Although cognitive control was related to surface area of the anterior
      cingulate independently of basic processes of mental speed, the relationship
      between white matter quality and cognitive control could be fully accounted for
      by speed. The results underscore the need for integration of different aspects of
      brain maturation to understand the foundations of cognitive development.

PMID- 23150549
TI  - Injectable preformed scaffolds with shape-memory properties.
AB  - Injectable biomaterials are increasingly being explored to minimize risks and
      complications associated with surgical implantation. We describe a strategy for
      delivery via conventional needle-syringe injection of large preformed macroporous
      scaffolds with well-defined properties. Injectable 3D scaffolds, in the form of
      elastic sponge-like matrices, were prepared by environmentally friendly
      cryotropic gelation of a naturally sourced polymer. Cryogels with shape-memory
      properties may be molded to a variety of shapes and sizes, and may be optionally
      loaded with therapeutic agents or cells. These scaffolds have the capability to
      withstand reversible deformations at over 90% strain level, and a rapid
      volumetric recovery allows the structurally defined scaffolds to be injected
      through a small-bore needle with nearly complete geometric restoration once
      delivered. These gels demonstrated long-term release of biomolecules in vivo.
      Furthermore, cryogels impregnated with bioluminescent reporter cells provided
      enhanced survival, higher local retention, and extended engraftment of
      transplanted cells at the injection site compared with a standard injection
      technique. These injectable scaffolds show great promise for various biomedical
      applications, including cell therapies.

PMID- 23150552
TI  - Sculpting of an erodible body by flowing water.
AB  - Erosion by flowing fluids carves striking landforms on Earth and also provides
      important clues to the past and present environments of other worlds. In these
      processes, solid boundaries both influence and are shaped by the surrounding
      fluid, but the emergence of morphology as a result of this interaction is not
      well understood. We study the coevolution of shape and flow in the context of
      erodible bodies molded from clay and immersed in a fast, unidirectional water
      flow. Although commonly viewed as a smoothing process, we find that erosion
      sculpts pointed and cornerlike features that persist as the solid shrinks. We
      explain these observations using flow visualization and a fluid mechanical model
      in which the surface shear stress dictates the rate of material removal.
      Experiments and simulations show that this interaction ultimately leads to self
      similarly receding boundaries and a unique front surface characterized by nearly
      uniform shear stress. This tendency toward conformity of stress offers a
      principle for understanding erosion in more complex geometries and flows, such as
      those present in nature.

PMID- 23150551
TI  - A critical role for Mnt in Myc-driven T-cell proliferation and oncogenesis.
AB  - Mnt (Max's next tango) is a Max-interacting transcriptional repressor that can
      antagonize both the proproliferative and proapoptotic functions of Myc in vitro.
      To ascertain the physiologically relevant functions of Mnt and to help define the
      relationship between Mnt and Myc in vivo, we generated a series of mouse strains
      in which Mnt was deleted in T cells in the absence of endogenous c-Myc or in the
      presence of ectopic c-Myc. We found that apoptosis caused by loss of Mnt did not
      require Myc but that ectopic Myc expression dramatically decreased the survival
      of both Mnt-deficient T cells in vivo and Mnt-deficient MEFs in vitro.
      Consequently, Myc-driven proliferative expansion of T cells in vitro and thymoma
      formation in vivo were prevented by the absence of Mnt. Consistent with T-cell
      models, mouse embryo fibroblasts (MEFs) lacking Mnt were refractory to oncogenic
      transformation by Myc. Tumor suppression caused by loss of Mnt was linked to
      increased apoptosis mediated by reactive oxygen species (ROS). Thus, although
      theoretically and experimentally a Myc antagonist, the dominant physiological
      role of Mnt appears to be suppression of apoptosis. Our results redefine the
      physiological relationship between Mnt and Myc and requirements for Myc-driven
      oncogenesis.

PMID- 23150553
TI  - Catalytic control of enzymatic fluorine specificity.
AB  - The investigation of unique chemical phenotypes has led to the discovery of
      enzymes with interesting behaviors that allow us to explore unusual function. The
      organofluorine-producing microbe Streptomyces cattleya has evolved a fluoroacetyl
      CoA thioesterase (FlK) that demonstrates a surprisingly high level of
      discrimination for a single fluorine substituent on its substrate compared with
      the cellularly abundant hydrogen analog, acetyl-CoA. In this report, we show that
      the high selectivity of FlK is achieved through catalysis rather than molecular
      recognition, where deprotonation at the C(alpha) position to form a putative
      ketene intermediate only occurs on the fluorinated substrate, thereby
      accelerating the rate of hydrolysis 10(4)-fold compared with the nonfluorinated
      congener. These studies provide insight into mechanisms of catalytic selectivity
      in a native system where the existence of two reaction pathways determines
      substrate rather than product selection.

PMID- 23150554
TI  - Epitranscriptional orchestration of genetic reprogramming is an emergent property
      of stress-regulated cardiac microRNAs.
AB  - Cardiac stress responses are driven by an evolutionarily conserved gene
      expression program comprising dozens of microRNAs and hundreds of mRNAs.
      Functionalities of different individual microRNAs are being studied, but the
      overall purpose of interactions between stress-regulated microRNAs and mRNAs and
      potentially distinct roles for microRNA-mediated epigenetic and conventional
      transcriptional genetic reprogramming of the stressed heart are unknown. Here we
      used deep sequencing to interrogate microRNA and mRNA regulation in pressure
      overloaded mouse hearts, and performed a genome-wide examination of microRNA-mRNA
      interactions during early cardiac hypertrophy. Based on abundance and regulatory
      patterns, cardiac microRNAs were categorized as constitutively expressed
      housekeeping, regulated homeostatic, or dynamic early stress-responsive
      microRNAs. Regulation of 62 stress-responsive cardiac microRNAs directly affected
      levels of only 66 mRNAs, but the global impact of microRNA-mediated epigenetic
      regulation was amplified by preferential targeting of mRNAs encoding
      transcription factors, kinases, and phosphatases exerting amplified secondary
      effects. Thus, an emergent cooperative property of stress-regulated microRNAs is
      orchestration of transcriptional and posttranslational events that help determine
      the stress-reactive cardiac phenotype. This global functionality explains how
      large end-organ effects can be induced through modest individual changes in
      target mRNA and protein content by microRNAs that sense and respond dynamically
      to a changing physiological milieu.

PMID- 23150555
TI  - Role for kisspeptin/neurokinin B/dynorphin (KNDy) neurons in cutaneous
      vasodilatation and the estrogen modulation of body temperature.
AB  - Estrogen withdrawal in menopausal women leads to hot flushes, a syndrome
      characterized by the episodic activation of heat dissipation effectors. Despite
      the extraordinary number of individuals affected, the etiology of flushes remains
      an enigma. Because menopause is accompanied by marked alterations in hypothalamic
      kisspeptin/neurokinin B/dynorphin (KNDy) neurons, we hypothesized that these
      neurons could contribute to the generation of flushes. To determine if KNDy
      neurons participate in the regulation of body temperature, we evaluated the
      thermoregulatory effects of ablating KNDy neurons by injecting a selective toxin
      for neurokinin-3 expressing neurons [NK(3)-saporin (SAP)] into the rat arcuate
      nucleus. Remarkably, KNDy neuron ablation consistently reduced tail-skin
      temperature (T(SKIN)), indicating that KNDy neurons facilitate cutaneous
      vasodilatation, an important heat dissipation effector. Moreover, KNDy ablation
      blocked the reduction of T(SKIN) by 17beta-estradiol (E(2)), which occurred in
      the environmental chamber during the light phase, but did not affect the E(2)
      suppression of T(SKIN) during the dark phase. At the high ambient temperature of
      33  degrees C, the average core temperature (T(CORE)) of ovariectomized (OVX)
      control rats was significantly elevated, and this value was reduced by E(2)
      replacement. In contrast, the average T(CORE) of OVX, KNDy-ablated rats was lower
      than OVX control rats at 33  degrees C, and not altered by E(2) replacement.
      These data provide unique evidence that KNDy neurons promote cutaneous
      vasodilatation and participate in the E(2) modulation of body temperature.
      Because cutaneous vasodilatation is a cardinal sign of a hot flush, these results
      support the hypothesis that KNDy neurons could play a role in the generation of
      flushes.

PMID- 23150556
TI  - Linking ligand perception by PEPR pattern recognition receptors to cytosolic Ca2+
      elevation and downstream immune signaling in plants.
AB  - Little is known about molecular steps linking perception of pathogen invasion by
      cell surface sentry proteins acting as pattern recognition receptors (PRRs) to
      downstream cytosolic Ca(2+) elevation, a critical step in plant immune signaling
      cascades. Some PRRs recognize molecules (such as flagellin) associated with
      microbial pathogens (pathogen-associated molecular patterns, PAMPs), whereas
      others bind endogenous plant compounds (damage-associated molecular patterns,
      DAMPs) such as peptides released from cells upon attack. This work focuses on the
      Arabidopsis DAMPs plant elicitor peptides (Peps) and their receptors, PEPR1 and
      PEPR2. Pep application causes in vivo cGMP generation and downstream signaling
      that is lost when the predicted PEPR receptor guanylyl cyclase (GC) active site
      is mutated. Pep-induced Ca(2+) elevation is attributable to cGMP activation of a
      Ca(2+) channel. Some differences were identified between Pep/PEPR signaling and
      the Ca(2+)-dependent immune signaling initiated by the flagellin peptide flg22
      and its cognate receptor Flagellin-sensing 2 (FLS2). FLS2 signaling may have a
      greater requirement for intracellular Ca(2+) stores and inositol phosphate
      signaling, whereas Pep/PEPR signaling requires extracellular Ca(2+). Maximal FLS2
      signaling requires a functional Pep/PEPR system. This dependence was evidenced as
      a requirement for functional PEPR receptors for maximal flg22-dependent Ca(2+)
      elevation, H(2)O(2) generation, defense gene [WRKY33 and Plant Defensin 1.2
      (PDF1.2)] expression, and flg22/FLS2-dependent impairment of pathogen growth. In
      a corresponding fashion, FLS2 loss of function impaired Pep signaling. In
      addition, a role for PAMP and DAMP perception in bolstering effector-triggered
      immunity (ETI) is reported; loss of function of either FLS2 or PEPR receptors
      impaired the hypersensitive response (HR) to an avirulent pathogen.

PMID- 23150557
TI  - Optimizing the temporal dynamics of light to human perception.
AB  - No previous research has tuned the temporal characteristics of light-emitting
      devices to enhance brightness perception in human vision, despite the potential
      for significant power savings. The role of stimulus duration on perceived
      contrast is unclear, due to contradiction between the models proposed by Bloch
      and by Broca and Sulzer over 100 years ago. We propose that the discrepancy is
      accounted for by the observer's "inherent expertise bias," a type of experimental
      bias in which the observer's life-long experience with interpreting the sensory
      world overcomes perceptual ambiguities and biases experimental outcomes. By
      controlling for this and all other known biases, we show that perceived contrast
      peaks at durations of 50-100 ms, and we conclude that the Broca-Sulzer effect
      best describes human temporal vision. We also show that the plateau in perceived
      brightness with stimulus duration, described by Bloch's law, is a previously
      uncharacterized type of temporal brightness constancy that, like classical
      constancy effects, serves to enhance object recognition across varied lighting
      conditions in natural vision-although this is a constancy effect that normalizes
      perception across temporal modulation conditions. A practical outcome of this
      study is that tuning light-emitting devices to match the temporal dynamics of the
      human visual system's temporal response function will result in significant power
      savings.

PMID- 23150558
TI  - Fluctuating shells under pressure.
AB  - Thermal fluctuations strongly modify the large length-scale elastic behavior of
      cross-linked membranes, giving rise to scale-dependent elastic moduli. Whereas
      thermal effects in flat membranes are well understood, many natural and
      artificial microstructures are modeled as thin elastic shells. Shells are
      distinguished from flat membranes by their nonzero curvature, which provides a
      size-dependent coupling between the in-plane stretching modes and the out-of
      plane undulations. In addition, a shell can support a pressure difference between
      its interior and its exterior. Little is known about the effect of thermal
      fluctuations on the elastic properties of shells. Here, we study the statistical
      mechanics of shape fluctuations in a pressurized spherical shell, using
      perturbation theory and Monte Carlo computer simulations, explicitly including
      the effects of curvature and an inward pressure. We predict novel properties of
      fluctuating thin shells under point indentations and pressure-induced
      deformations. The contribution due to thermal fluctuations increases with
      increasing ratio of shell radius to thickness and dominates the response when the
      product of this ratio and the thermal energy becomes large compared with the
      bending rigidity of the shell. Thermal effects are enhanced when a large uniform
      inward pressure acts on the shell and diverge as this pressure approaches the
      classical buckling transition of the shell. Our results are relevant for the
      elasticity and osmotic collapse of microcapsules.

PMID- 23150559
TI  - ARL13B, PDE6D, and CEP164 form a functional network for INPP5E ciliary targeting.
AB  - Mutations affecting ciliary components cause a series of related genetic
      disorders in humans, including nephronophthisis (NPHP), Joubert syndrome (JBTS),
      Meckel-Gruber syndrome (MKS), and Bardet-Biedl syndrome (BBS), which are
      collectively termed "ciliopathies." Recent protein-protein interaction studies
      combined with genetic analyses revealed that ciliopathy-related proteins form
      several functional networks/modules that build and maintain the primary cilium.
      However, the precise function of many ciliopathy-related proteins and the
      mechanisms by which these proteins are targeted to primary cilia are still not
      well understood. Here, we describe a protein-protein interaction network of
      inositol polyphosphate-5-phosphatase E (INPP5E), a prenylated protein associated
      with JBTS, and its ciliary targeting mechanisms. INPP5E is targeted to the
      primary cilium through a motif near the C terminus and prenyl-binding protein
      phosphodiesterase 6D (PDE6D)-dependent mechanisms. Ciliary targeting of INPP5E is
      facilitated by another JBTS protein, ADP-ribosylation factor-like 13B (ARL13B),
      but not by ARL2 or ARL3. ARL13B missense mutations that cause JBTS in humans
      disrupt the ARL13B-INPP5E interaction. We further demonstrate interactions of
      INPP5E with several ciliary and centrosomal proteins, including a recently
      identified ciliopathy protein centrosomal protein 164 (CEP164). These findings
      indicate that ARL13B, INPP5E, PDE6D, and CEP164 form a distinct functional
      network that is involved in JBTS and NPHP but independent of the ones previously
      defined by NPHP and MKS proteins.

PMID- 23150560
TI  - Function of glycoprotein E of herpes simplex virus requires coordinated assembly
      of three tegument proteins on its cytoplasmic tail.
AB  - Glycoprotein E (gE) of HSV plays a key role in cell-to-cell spread and virus
      induced cell fusion. Here, we report that this function of gE requires the
      cooperation of tegument proteins UL11, UL16, and UL21. We found that the four
      proteins come together with very high efficiency to form a complex in transfected
      cells and in a manner that is regulated and coordinated. In particular, the
      inefficient interaction of UL16 with each membrane protein (UL11 and gE) observed
      in pairwise transfections became efficient when other binding partners were
      present. The significance of these interactions was revealed in studies of viral
      mutants, which showed that each of these tegument proteins is critical for
      processing, transport, and biological activity of gE. These findings provide
      insights into the mechanisms of how gE executes its function and also have
      implications in understanding HSV assembly and budding.

PMID- 23150561
TI  - Bidirectional influence of sodium channel activation on NMDA receptor-dependent
      cerebrocortical neuron structural plasticity.
AB  - Neuronal activity regulates brain development and synaptic plasticity through N
      methyl-D-aspartate receptors (NMDARs) and calcium-dependent signaling pathways.
      Intracellular sodium ([Na(+)](i)) also exerts a regulatory influence on NMDAR
      channel activity, and [Na(+)](i) may, therefore, function as a signaling
      molecule. In an attempt to mimic the influence of neuronal activity on synaptic
      plasticity, we used brevetoxin-2 (PbTx-2), a voltage-gated sodium channel (VGSC)
      gating modifier, to manipulate [Na(+)](i) in cerebrocortical neurons. The acute
      application of PbTx-2 produced concentration-dependent increments in both
      intracellular [Na(+)] and [Ca(2+)]. Pharmacological evaluation showed that PbTx-2
      induced Ca(2+) influx primarily involved VGSC activation and NMDAR-mediated
      entry. Additionally, PbTx-2 robustly potentiated NMDA-induced Ca(2+) influx. PbTx
      2-exposed neurons showed enhanced neurite outgrowth, increased dendritic arbor
      complexity, and increased dendritic filopodia density. The appearance of
      spontaneous calcium oscillations, reflecting synchronous neuronal activity, was
      accelerated by PbTx-2 treatment. Parallel to this response, PbTx-2 increased
      cerebrocortical neuron synaptic density. PbTx-2 stimulation of neurite outgrowth,
      dendritic arborization, and synaptogenesis all exhibited bidirectional
      concentration-response profiles. This profile paralleled that of NMDA, which also
      produced bidirectional concentration-response profiles for neurite outgrowth and
      synaptogenesis. These data are consistent with the hypothesis that PbTx-2
      enhanced neuronal plasticity involves NMDAR-dependent signaling. Our results
      demonstrate that PbTx-2 mimics activity-dependent neuronal structural plasticity
      in cerebrocortical neurons through an increase in [Na(+)](i), up-regulation of
      NMDAR function, and engagement of downstream Ca(2+)-dependent signaling pathways.
      These data suggest that VGSC gating modifiers may represent a pharmacologic
      strategy to regulate neuronal plasticity through NMDAR-dependent mechanisms.

PMID- 23150562
TI  - FoxO is a critical regulator of stem cell maintenance in immortal Hydra.
AB  - Hydra's unlimited life span has long attracted attention from natural scientists.
      The reason for that phenomenon is the indefinite self-renewal capacity of its
      stem cells. The underlying molecular mechanisms have yet to be explored. Here, by
      comparing the transcriptomes of Hydra's stem cells followed by functional
      analysis using transgenic polyps, we identified the transcription factor forkhead
      box O (FoxO) as one of the critical drivers of this continuous self-renewal. foxO
      overexpression increased interstitial stem cell and progenitor cell proliferation
      and activated stem cell genes in terminally differentiated somatic cells. foxO
      down-regulation led to an increase in the number of terminally differentiated
      cells, resulting in a drastically reduced population growth rate. In addition, it
      caused down-regulation of stem cell genes and antimicrobial peptide (AMP)
      expression. These findings contribute to a molecular understanding of Hydra's
      immortality, indicate an evolutionarily conserved role of FoxO in controlling
      longevity from Hydra to humans, and have implications for understanding cellular
      aging.

PMID- 23150564
TI  - Carbon dioxide reduction to methane and coupling with acetylene to form propylene
      catalyzed by remodeled nitrogenase.
AB  - A doubly substituted form of the nitrogenase MoFe protein (alpha-70(Val)(->Ala),
      alpha-195(His->Gln)) has the capacity to catalyze the reduction of carbon dioxide
      (CO(2)) to yield methane (CH(4)). Under optimized conditions, 1 nmol of the
      substituted MoFe protein catalyzes the formation of 21 nmol of CH(4) within 20
      min. The catalytic rate depends on the partial pressure of CO(2) (or
      concentration of HCO(3)(-)) and the electron flux through nitrogenase. The doubly
      substituted MoFe protein also has the capacity to catalyze the unprecedented
      formation of propylene (H(2)C = CH-CH(3)) through the reductive coupling of CO(2)
      and acetylene (HC=CH). In light of these observations, we suggest that an
      emerging understanding of the mechanistic features of nitrogenase could be
      relevant to the design of synthetic catalysts for CO(2) sequestration and
      formation of olefins.

PMID- 23150565
TI  - Exploring conformational states of the bacterial voltage-gated sodium channel
      NavAb via molecular dynamics simulations.
AB  - The X-ray structure of the bacterial voltage-gated sodium channel NavAb has been
      reported in a conformation with a closed conduction pore. Comparison between this
      structure and the activated-open and resting-closed structures of the voltage
      gated Kv1.2 potassium channel suggests that the voltage-sensor domains (VSDs) of
      the reported structure are not fully activated. Using the aforementioned
      structures of Kv1.2 as templates, molecular dynamics simulations are used to
      identify analogous functional conformations of NavAb. Specifically, starting from
      the NavAb crystal structure, conformations of the membrane-bound channel are
      sampled along likely pathways for activation of the VSD and opening of the pore
      domain. Gating charge computations suggest that a structural rearrangement
      comparable to that occurring between activated-open and resting-closed states is
      required to explain experimental values of the gating charge, thereby confirming
      that the reported VSD structure is likely an intermediate along the channel
      activation pathway. Our observation that the X-ray structure exhibits a low pore
      domain-opening propensity further supports this notion. The present molecular
      dynamics study also identifies conformations of NavAb that are seemingly related
      to the resting-closed and activated-open states. Our findings are consistent with
      recent structural and functional studies of the orthologous channels NavRh,
      NaChBac, and NavMs and offer possible structures for the functionally relevant
      conformations of NavAb.

PMID- 23150567
TI  - Molecular response in one-photon absorption via natural thermal light vs. pulsed
      laser excitation.
AB  - Photoinduced biological processes occur via one-photon absorption in natural
      light, which is weak, continuous wave, and incoherent, but are often studied in
      the laboratory using pulsed coherent light. Here, we compare the response of a
      molecule to these two very different sources within a quantized radiation field
      picture. The latter is shown to induce coherent time evolution in the molecule,
      whereas the former does not. As a result, the coherent time dependence observed
      in the laboratory experiments will not be relevant to the natural biological
      process. Emphasis is placed on resolving confusions regarding this issue that are
      shown to arise from aspects of quantum measurement and from a lack of
      appreciation of the proper description of the absorbed photon.

PMID- 23150569
TI  - Averaging principle for second-order approximation of heterogeneous models with
      homogeneous models.
AB  - Typically, models with a heterogeneous property are considerably harder to
      analyze than the corresponding homogeneous models, in which the heterogeneous
      property is replaced by its average value. In this study we show that any outcome
      of a heterogeneous model that satisfies the two properties of differentiability
      and symmetry is O(epsilon(2)) equivalent to the outcome of the corresponding
      homogeneous model, where epsilon is the level of heterogeneity. We then use this
      averaging principle to obtain new results in queuing theory, game theory
      (auctions), and social networks (marketing).

PMID- 23150568
TI  - Inducible, reversible system for the rapid and complete degradation of proteins
      in mammalian cells.
AB  - Inducible degradation is a powerful approach for identifying the function of a
      specific protein or protein complex. Recently, a plant auxin-inducible degron
      (AID) system has been shown to degrade AID-tagged target proteins in nonplant
      cells. Here, we demonstrate that an AID-tagged protein can functionally replace
      an endogenous protein depleted by RNAi, leading to an inducible null phenotype
      rapidly after auxin addition. The AID system is shown to be capable of
      controlling the stability of AID-tagged proteins that are in either nuclear or
      cytoplasmic compartments and even when incorporated into protein complexes.
      Induced degradation occurs rapidly after addition of auxin with protein half-life
      reduced to as little as 9 min and proceeding to completion with first-order
      kinetics. AID-mediated instability is demonstrated to be rapidly reversible.
      Induced degradation is shown to initiate and continue in all cell cycle phases,
      including mitosis, making this system especially useful for identifying the
      function(s) of proteins of interest during specific points in the mammalian cell
      cycle.

PMID- 23150570
TI  - Hierarchical mesoporous perovskite La0.5Sr0.5CoO2.91 nanowires with ultrahigh
      capacity for Li-air batteries.
AB  - Lithium-air batteries have captured worldwide attention due to their highest
      energy density among the chemical batteries. To provide continuous oxygen
      channels, here, we synthesized hierarchical mesoporous perovskite
      La(0.5)Sr(0.5)CoO(2.91) (LSCO) nanowires. We tested the intrinsic oxygen
      reduction reaction (ORR) and oxygen evolution reaction (OER) activity in both
      aqueous electrolytes and nonaqueous electrolytes via rotating disk electrode
      (RDE) measurements and demonstrated that the hierarchical mesoporous LSCO
      nanowires are high-performance catalysts for the ORR with low peak-up potential
      and high limiting diffusion current. Furthermore, we fabricated Li-air batteries
      on the basis of hierarchical mesoporous LSCO nanowires and nonaqueous
      electrolytes, which exhibited ultrahigh capacity, ca. over 11,000 mAh?g(-1), one
      order of magnitude higher than that of LSCO nanoparticles. Besides, the possible
      reaction mechanism is proposed to explain the catalytic activity of the LSCO
      mesoporous nanowire.

PMID- 23150571
TI  - Unexpected nondenitrifier nitrous oxide reductase gene diversity and abundance in
      soils.
AB  - Agricultural and industrial practices more than doubled the intrinsic rate of
      terrestrial N fixation over the past century with drastic consequences, including
      increased atmospheric nitrous oxide (N(2)O) concentrations. N(2)O is a potent
      greenhouse gas and contributor to ozone layer destruction, and its release from
      fixed N is almost entirely controlled by microbial activities. Mitigation of
      N(2)O emissions to the atmosphere has been attributed exclusively to denitrifiers
      possessing NosZ, the enzyme system catalyzing N(2)O to N(2) reduction. We
      demonstrate that diverse microbial taxa possess divergent nos clusters with genes
      that are related yet evolutionarily distinct from the typical nos genes of
      denitirifers. nos clusters with atypical nosZ occur in Bacteria and Archaea that
      denitrify (44% of genomes), do not possess other denitrification genes (56%), or
      perform dissimilatory nitrate reduction to ammonium (DNRA; (31%). Experiments
      with the DNRA soil bacterium Anaeromyxobacter dehalogenans demonstrated that the
      atypical NosZ is an effective N(2)O reductase, and PCR-based surveys suggested
      that atypical nosZ are abundant in terrestrial environments. Bioinformatic
      analyses revealed that atypical nos clusters possess distinctive regulatory and
      functional components (e.g., Sec vs. Tat secretion pathway in typical nos), and
      that previous nosZ-targeted PCR primers do not capture the atypical nosZ
      diversity. Collectively, our results suggest that nondenitrifying populations
      with a broad range of metabolisms and habitats are potentially significant
      contributors to N(2)O consumption. Apparently, a large, previously unrecognized
      group of environmental nosZ has not been accounted for, and characterizing their
      contributions to N(2)O consumption will advance understanding of the ecological
      controls on N(2)O emissions and lead to refined greenhouse gas flux models.

PMID- 23150572
TI  - Measurement of energy landscape roughness of folded and unfolded proteins.
AB  - The dynamics of protein conformational changes, from protein folding to smaller
      changes, such as those involved in ligand binding, are governed by the properties
      of the conformational energy landscape. Different techniques have been used to
      follow the motion of a protein over this landscape and thus quantify its
      properties. However, these techniques often are limited to short timescales and
      low-energy conformations. Here, we describe a general approach that overcomes
      these limitations. Starting from a nonnative conformation held by an aromatic
      disulfide bond, we use time-resolved spectroscopy to observe nonequilibrium
      backbone dynamics over nine orders of magnitude in time, from picoseconds to
      milliseconds, after photolysis of the disulfide bond. We find that the
      reencounter probability of residues that initially are in close contact decreases
      with time following an unusual power law that persists over the full time range
      and is independent of the primary sequence. Model simulations show that this
      power law arises from subdiffusional motion, indicating a wide distribution of
      trapping times in local minima of the energy landscape, and enable us to quantify
      the roughness of the energy landscape (4-5 k(B)T). Surprisingly, even under
      denaturing conditions, the energy landscape remains highly rugged with deep traps
      (>20 k(B)T) that result from multiple nonnative interactions and are sufficient
      for trapping on the millisecond timescale. Finally, we suggest that the
      subdiffusional motion of the protein backbone found here may promote rapid
      folding of proteins with low contact order by enhancing contact formation between
      nearby residues.

PMID- 23150573
TI  - Nucleosome-depleted chromatin gaps recruit assembly factors for the H3.3 histone
      variant.
AB  - Most nucleosomes that package eukaryotic DNA are assembled during DNA
      replication, but chromatin structure is routinely disrupted in active regions of
      the genome. Replication-independent nucleosome replacement using the H3.3 histone
      variant efficiently repackages these regions, but how histones are recruited to
      these sites is unknown. Here, we use an inducible system that produces nucleosome
      depleted chromatin at the Hsp70 genes in Drosophila to define steps in the
      mechanism of nucleosome replacement. We find that the Xnp chromatin remodeler and
      the Hira histone chaperone independently bind nucleosome-depleted chromatin.
      Surprisingly, these two factors are only displaced when new nucleosomes are
      assembled. H3.3 deposition assays reveal that Xnp and Hira are required for
      efficient nucleosome replacement, and double-mutants are lethal. We propose that
      Xnp and Hira recognize exposed DNA and serve as a binding platform for the
      efficient recruitment of H3.3 predeposition complexes to chromatin gaps. These
      results uncover the mechanisms by which eukaryotic cells actively prevent the
      exposure of DNA in the nucleus.

PMID- 23150574
TI  - Electronic sensor and actuator webs for large-area complex geometry cardiac
      mapping and therapy.
AB  - Curved surfaces, complex geometries, and time-dynamic deformations of the heart
      create challenges in establishing intimate, nonconstraining interfaces between
      cardiac structures and medical devices or surgical tools, particularly over large
      areas. We constructed large area designs for diagnostic and therapeutic
      stretchable sensor and actuator webs that conformally wrap the epicardium,
      establishing robust contact without sutures, mechanical fixtures, tapes, or
      surgical adhesives. These multifunctional web devices exploit open, mesh layouts
      and mount on thin, bio-resorbable sheets of silk to facilitate handling in a way
      that yields, after dissolution, exceptionally low mechanical moduli and
      thicknesses. In vivo studies in rabbit and pig animal models demonstrate the
      effectiveness of these device webs for measuring and spatially mapping
      temperature, electrophysiological signals, strain, and physical contact in sheet
      and balloon-based systems that also have the potential to deliver energy to
      perform localized tissue ablation.

PMID- 23150575
TI  - Variable evolutionary routes to host establishment across repeated rabies virus
      host shifts among bats.
AB  - Determining the genetic pathways that viruses traverse to establish in new host
      species is crucial to predict the outcome of cross-species transmission but
      poorly understood for most host-virus systems. Using sequences encoding 78% of
      the rabies virus genome, we explored the extent, repeatability and dynamic
      outcome of evolution associated with multiple host shifts among New World bats.
      Episodic bursts of positive selection were detected in several viral proteins,
      including regions associated with host cell interaction and viral replication.
      Host shifts involved unique sets of substitutions, and few sites exhibited
      repeated evolution across adaptation to many bat species, suggesting diverse
      genetic determinants over host range. Combining these results with genetic
      reconstructions of the demographic histories of individual viral lineages
      revealed that although rabies viruses shared consistent three-stage processes of
      emergence in each new bat species, host shifts involving greater numbers of
      positively selected substitutions had longer delays between cross-species
      transmission and enzootic viral establishment. Our results point to multiple
      evolutionary routes to host establishment in a zoonotic RNA virus that may
      influence the speed of viral emergence.

PMID- 23150576
TI  - Proteasome allostery as a population shift between interchanging conformers.
AB  - Protein degradation plays a critical role in cellular homeostasis, in regulating
      the cell cycle, and in the generation of peptides that are used in the immune
      response. The 20S proteasome core particle (CP), a barrel-like structure
      consisting of four heptameric protein rings stacked axially on top of each other,
      is central to this process. CP function is controlled by activator complexes that
      bind 75 A away from sites catalyzing proteolysis, and biochemical data are
      consistent with an allosteric mechanism by which binding is communicated to
      distal active sites. However, little structural evidence has emerged from the
      high-resolution images of the CP. Using methyl TROSY NMR spectroscopy, we
      demonstrate that in solution, the CP interconverts between multiple conformations
      whose relative populations are shifted on binding of the 11S activator or
      mutation of residues that contact activators. These conformers differ in
      contiguous regions of structure that connect activator binding to the CP active
      sites, and changes in their populations lead to differences in substrate
      proteolysis patterns. Moreover, various active site modifications result in
      conformational changes to the activator binding site by modulating the relative
      populations of these same CP conformers. This distribution is also affected by
      the binding of a small-molecule allosteric inhibitor of proteolysis, chloroquine,
      suggesting an important avenue in the development of therapeutics for proteasome
      inhibition.

PMID- 23150577
TI  - Atypical angiopoietin-like protein that regulates ANGPTL3.
AB  - Angiopoietin-like proteins (ANGPTLs) play major roles in the trafficking and
      metabolism of lipids. Inactivation of ANGPTL3, a gene located in an intron of
      DOCK7, results in very low levels of LDL-cholesterol (C), HDL-C and triglyceride
      (TAG). We identified another ANGPTL family member, ANGPTL8, which is located in
      the corresponding intron of DOCK6. A variant in this family member (rs2278426,
      R59W) was associated with lower plasma LDL-C and HDL-C levels in three
      populations. ANGPTL8 is expressed in liver and adipose tissue, and circulates in
      plasma of humans. Expression of ANGPTL8 was reduced by fasting and increased by
      refeeding in both mice and humans. To examine the functional relationship between
      the two ANGPTL family members, we expressed ANGPTL3 at physiological levels alone
      or together with ANGPTL8 in livers of mice. Plasma TAG level did not change in
      mice expressing ANGPTL3 alone, whereas coexpression with ANGPTL8 resulted in
      hypertriglyceridemia, despite a reduction in circulating ANGPTL3. ANGPTL8
      coimmunoprecipitated with the N-terminal domain of ANGPTL3 in plasma of these
      mice. In cultured hepatocytes, ANGPTL8 expression increased the appearance of N
      terminal ANGPTL3 in the medium, suggesting ANGPTL8 may activate ANGPTL3.
      Consistent with this scenario, expression of ANGPTL8 in Angptl3(-/-) mice failed
      to promote hypertriglyceridemia. Thus, ANGPTL8, a paralog of ANGPTL3 that arose
      through duplication of an ancestral DOCK gene, regulates postprandial TAG and
      fatty acid metabolism by controlling activation of its progenitor, and perhaps
      other ANGPTLs. Inhibition of ANGPTL8 provides a new therapeutic strategy for
      reducing plasma lipoprotein levels.

PMID- 23150578
TI  - Anti-inflammatory lipoxin A4 is an endogenous allosteric enhancer of CB1
      cannabinoid receptor.
AB  - Allosteric modulation of G-protein-coupled receptors represents a key goal of
      current pharmacology. In particular, endogenous allosteric modulators might
      represent important targets of interventions aimed at maximizing therapeutic
      efficacy and reducing side effects of drugs. Here we show that the anti
      inflammatory lipid lipoxin A(4) is an endogenous allosteric enhancer of the CB(1)
      cannabinoid receptor. Lipoxin A(4) was detected in brain tissues, did not compete
      for the orthosteric binding site of the CB(1) receptor (vs. (3)H-SR141716A), and
      did not alter endocannabinoid metabolism (as opposed to URB597 and MAFP), but it
      enhanced affinity of anandamide at the CB1 receptor, thereby potentiating the
      effects of this endocannabinoid both in vitro and in vivo. In addition, lipoxin
      A(4) displayed a CB(1) receptor-dependent protective effect against beta-amyloid
      (1-40)-induced spatial memory impairment in mice. The discovery of lipoxins as a
      class of endogenous allosteric modulators of CB(1) receptors may foster the
      therapeutic exploitation of the endocannabinoid system, in particular for the
      treatment of neurodegenerative disorders.

PMID- 23150579
TI  - alphavbeta3-integrin is a major sensor and activator of innate immunity to herpes
      simplex virus-1.
AB  - Pathogens are sensed by Toll-like receptors (TLRs) and a growing number of non
      TLR receptors. Integrins constitute a family of signaling receptors exploited by
      viruses and bacteria to access cells. By gain- and loss-of-function approaches we
      found that alphavbeta3-integrin is a sensor of and plays a crucial role in the
      innate defense against herpes simplex virus (HSV). alphavbeta3-integrin signaled
      through two pathways. One concurred with TLR2, affected activation/induction of
      interferons type 1 (IFNs-1), NF-kappaB (nuclear factor kappa-light-chain-enhancer
      of activated B cells), and a polarized set of cytokines and receptors. The virion
      glycoproteins gH/gL sufficed to induce IFN1 and NF-kappaB via this pathway. The
      other pathway was TLR2-independent, involved sarcoma (SRC)-spleen tyrosine kinase
      (SYK)-Caspase recruitment domain-containing protein 9 (CARD9)-TRIF (TIR-domain
      containing adapter-inducing interferon-beta), and affected interferon regulatory
      factor 3 and 7 (IRF3-IRF7). The importance of alphavbeta3-integrin-mediated
      defense is reflected in the observation that HSV evolved the immediate-early
      infected cellular protein 0 (ICP0) protein to counteract it. We propose that
      alphavbeta3-integrin is considered a class of non-TLR pattern recognition
      receptors, a role likely exerted toward viruses and bacteria that interact with
      integrins and mount an innate response.

PMID- 23150580
TI  - Synergistic dual positive feedback loops established by molecular sequestration
      generate robust bimodal response.
AB  - Feedback loops are ubiquitous features of biological networks and can produce
      significant phenotypic heterogeneity, including a bimodal distribution of gene
      expression across an isogenic cell population. In this work, a combination of
      experiments and computational modeling was used to explore the roles of multiple
      feedback loops in the bimodal, switch-like response of the Saccharomyces
      cerevisiae galactose regulatory network. Here, we show that bistability underlies
      the observed bimodality, as opposed to stochastic effects, and that two unique
      positive feedback loops established by Gal1p and Gal3p, which both regulate
      network activity by molecular sequestration of Gal80p, induce this bimodality.
      Indeed, systematically scanning through different single and multiple feedback
      loop knockouts, we demonstrate that there is always a concentration regime that
      preserves the system's bimodality, except for the double deletion of GAL1 and the
      GAL3 feedback loop, which exhibits a graded response for all conditions tested.
      The constitutive production rates of Gal1p and Gal3p operate as bifurcation
      parameters because variations in these rates can also abolish the system's
      bimodal response. Our model indicates that this second loss of bistability ensues
      from the inactivation of the remaining feedback loop by the overexpressed
      regulatory component. More broadly, we show that the sequestration binding
      affinity is a critical parameter that can tune the range of conditions for
      bistability in a circuit with positive feedback established by molecular
      sequestration. In this system, two positive feedback loops can significantly
      enhance the region of bistability and the dynamic response time.

PMID- 23150582
TI  - The basis of musical consonance as revealed by congenital amusia.
AB  - Some combinations of musical notes sound pleasing and are termed "consonant," but
      others sound unpleasant and are termed "dissonant." The distinction between
      consonance and dissonance plays a central role in Western music, and its origins
      have posed one of the oldest and most debated problems in perception. In modern
      times, dissonance has been widely believed to be the product of "beating":
      interference between frequency components in the cochlea that has been believed
      to be more pronounced in dissonant than consonant sounds. However, harmonic
      frequency relations, a higher-order sound attribute closely related to pitch
      perception, has also been proposed to account for consonance. To tease apart
      theories of musical consonance, we tested sound preferences in individuals with
      congenital amusia, a neurogenetic disorder characterized by abnormal pitch
      perception. We assessed amusics' preferences for musical chords as well as for
      the isolated acoustic properties of beating and harmonicity. In contrast to
      control subjects, amusic listeners showed no preference for consonance, rating
      the pleasantness of consonant chords no higher than that of dissonant chords.
      Amusics also failed to exhibit the normally observed preference for harmonic over
      inharmonic tones, nor could they discriminate such tones from each other. Despite
      these abnormalities, amusics exhibited normal preferences and discrimination for
      stimuli with and without beating. This dissociation indicates that, contrary to
      classic theories, beating is unlikely to underlie consonance. Our results instead
      suggest the need to integrate harmonicity as a foundation of music preferences,
      and illustrate how amusia may be used to investigate normal auditory function.

PMID- 23150581
TI  - Bacteria of the human gut microbiome catabolize red seaweed glycans with
      carbohydrate-active enzyme updates from extrinsic microbes.
AB  - Humans host an intestinal population of microbes--collectively referred to as the
      gut microbiome--which encode the carbohydrate active enzymes, or CAZymes, that
      are absent from the human genome. These CAZymes help to extract energy from
      recalcitrant polysaccharides. The question then arises as to if and how the
      microbiome adapts to new carbohydrate sources when modern humans change eating
      habits. Recent metagenome analysis of microbiomes from healthy American,
      Japanese, and Spanish populations identified putative CAZymes obtained by
      horizontal gene transfer from marine bacteria, which suggested that human gut
      bacteria evolved to degrade algal carbohydrates-for example, consumed in form of
      sushi. We approached this hypothesis by studying such a polysaccharide
      utilization locus (PUL) obtained by horizontal gene transfer by the gut bacterium
      Bacteroides plebeius. Transcriptomic and growth experiments revealed that the PUL
      responds to the polysaccharide porphyran from red algae, enabling growth on this
      carbohydrate but not related substrates like agarose and carrageenan. The X-ray
      crystallographic and biochemical analysis of two proteins encoded by this PUL,
      BACPLE_01689 and BACPLE_01693, showed that they are beta-porphyranases belonging
      to glycoside hydrolase families 16 and 86, respectively. The product complex of
      the GH86 at 1.3 A resolution highlights the molecular details of porphyran
      hydrolysis by this new porphyranase. Combined, these data establish experimental
      support for the argument that CAZymes and associated genes obtained from
      extrinsic microbes add new catabolic functions to the human gut microbiome.

PMID- 23150583
TI  - Isotopic evidence for an early shift to C4 resources by Pliocene hominins in
      Chad.
AB  - Foods derived from C(4) plants were important in the dietary ecology of early
      Pleistocene hominins in southern and eastern Africa, but the origins and
      geographic variability of this relationship remain unknown. Carbon isotope data
      show that Australopithecus bahrelghazali individuals from Koro Toro in Chad are
      significantly enriched in (13)C, indicating a dependence on C(4) resources. As
      these sites are over 3 million years in age, the results extend the pattern of
      C(4) dependence seen in Paranthropus boisei in East Africa by more than 1.5
      million years. The Koro Toro hominin fossils were found in argillaceous sandstone
      levels along with abundant grazing and aquatic faunal elements that, in
      combination, indicate the presence of open to wooded grasslands and stream
      channels associated with a greatly enlarged Lake Chad. In such an environment,
      the most abundant C(4) plant resources available to A. bahrelghazali were grasses
      and sedges, neither of which is usually considered as standard great ape fare.
      The results suggest an early and fundamental shift in hominin dietary ecology
      that facilitated the exploitation of new habitats.

PMID- 23150584
TI  - Human mitochondrial holocytochrome c synthase's heme binding, maturation
      determinants, and complex formation with cytochrome c.
AB  - Proper functioning of the mitochondrion requires the orchestrated assembly of
      respiratory complexes with their cofactors. Cytochrome c, an essential electron
      carrier in mitochondria and a critical component of the apoptotic pathway,
      contains a heme cofactor covalently attached to the protein at a conserved CXXCH
      motif. Although it has been known for more than two decades that heme attachment
      requires the mitochondrial protein holocytochrome c synthase (HCCS), the
      mechanism remained unknown. We purified membrane-bound human HCCS with endogenous
      heme and in complex with its cognate human apocytochrome c. Spectroscopic
      analyses of HCCS alone and complexes of HCCS with site-directed variants of
      cytochrome c revealed the fundamental steps of heme attachment and maturation. A
      conserved histidine in HCCS (His154) provided the key ligand to the heme iron.
      Formation of the HCCS:heme complex served as the platform for interaction with
      apocytochrome c. Heme was the central molecule mediating contact between HCCS and
      apocytochrome c. A conserved histidine in apocytochrome c (His19 of CXXCH)
      supplied the second axial ligand to heme in the trapped HCCS:heme:cytochrome c
      complex. We also examined the substrate specificity of human HCCS and converted a
      bacterial cytochrome c into a robust substrate for the HCCS. The results allow us
      to describe the molecular mechanisms underlying the HCCS reaction.

PMID- 23150585
TI  - Host epithelial geometry regulates breast cancer cell invasiveness.
AB  - Breast tumor development is regulated in part by cues from the local
      microenvironment, including interactions with neighboring nontumor cells as well
      as the ECM. Studies using homogeneous populations of breast cancer cell lines
      cultured in 3D ECM have shown that increased ECM stiffness stimulates tumor cell
      invasion. However, at early stages of breast cancer development, malignant cells
      are surrounded by normal epithelial cells, which have been shown to exert a tumor
      suppressive effect on cocultured cancer cells. Here we explored how the
      biophysical characteristics of the host microenvironment affect the proliferative
      and invasive tumor phenotype of the earliest stages of tumor development, by
      using a 3D microfabrication-based approach to engineer ducts composed of normal
      mammary epithelial cells that contained a single tumor cell. We found that the
      phenotype of the tumor cell was dictated by its position in the duct:
      proliferation and invasion were enhanced at the ends and blocked when the tumor
      cell was located elsewhere within the tissue. Regions of invasion correlated with
      high endogenous mechanical stress, as shown by finite element modeling and bead
      displacement experiments, and modulating the contractility of the host epithelium
      controlled the subsequent invasion of tumor cells. Combining microcomputed
      tomographic analysis with finite element modeling suggested that predicted
      regions of high mechanical stress correspond to regions of tumor formation in
      vivo. This work suggests that the mechanical tone of nontumorigenic host
      epithelium directs the phenotype of tumor cells and provides additional insight
      into the instructive role of the mechanical tumor microenvironment.

PMID- 23150586
TI  - Bioinspired multivalent DNA network for capture and release of cells.
AB  - Capture and isolation of flowing cells and particulates from body fluids has
      enormous implications in diagnosis, monitoring, and drug testing, yet monovalent
      adhesion molecules used for this purpose result in inefficient cell capture and
      difficulty in retrieving the captured cells. Inspired by marine creatures that
      present long tentacles containing multiple adhesive domains to effectively
      capture flowing food particulates, we developed a platform approach to capture
      and isolate cells using a 3D DNA network comprising repeating adhesive aptamer
      domains that extend over tens of micrometers into the solution. The DNA network
      was synthesized from a microfluidic surface by rolling circle amplification where
      critical parameters, including DNA graft density, length, and sequence, could
      readily be tailored. Using an aptamer that binds to protein tyrosine kinase-7
      (PTK7) that is overexpressed on many human cancer cells, we demonstrate that the
      3D DNA network significantly enhances the capture efficiency of lymphoblast CCRF
      CEM cells over monovalent aptamers and antibodies, yet maintains a high purity of
      the captured cells. When incorporated in a herringbone microfluidic device, the
      3D DNA network not only possessed significantly higher capture efficiency than
      monovalent aptamers and antibodies, but also outperformed previously reported
      cell-capture microfluidic devices at high flow rates. This work suggests that 3D
      DNA networks may have broad implications for detection and isolation of cells and
      other bioparticles.

PMID- 23150587
TI  - Dynamic force sensing of filamin revealed in single-molecule experiments.
AB  - Mechanical forces are important signals for cell response and development, but
      detailed molecular mechanisms of force sensing are largely unexplored. The
      cytoskeletal protein filamin is a key connecting element between the cytoskeleton
      and transmembrane complexes such as integrins or the von Willebrand receptor
      glycoprotein Ib. Here, we show using single-molecule mechanical measurements that
      the recently reported Ig domain pair 20-21 of human filamin A acts as an
      autoinhibited force-activatable mechanosensor. We developed a mechanical single
      molecule competition assay that allows online observation of binding events of
      target peptides in solution to the strained domain pair. We find that filamin
      force sensing is a highly dynamic process occurring in rapid equilibrium that
      increases the affinity to the target peptides by up to a factor of 17 between 2
      and 5 pN. The equilibrium mechanism we find here can offer a general scheme for
      cellular force sensing.

PMID- 23150588
TI  - Phototactic personality in fruit flies and its suppression by serotonin and
      white.
AB  - Drosophila typically move toward light (phototax positively) when startled. The
      various species of Drosophila exhibit some variation in their respective mean
      phototactic behaviors; however, it is not clear to what extent genetically
      identical individuals within each species behave idiosyncratically. Such
      behavioral individuality has indeed been observed in laboratory arthropods;
      however, the neurobiological factors underlying individual-to-individual
      behavioral differences are unknown. We developed "FlyVac," a high-throughput
      device for automatically assessing phototaxis in single animals in parallel. We
      observed surprising variability within every species and strain tested, including
      identically reared, isogenic strains. In an extreme example, a domesticated
      strain of Drosophila simulans harbored both strongly photopositive and strongly
      photonegative individuals. The particular behavior of an individual fly is not
      heritable and, because it persists for its lifetime, constitutes a model system
      for elucidating the molecular mechanisms of personality. Although all strains
      assayed had greater than expected variation (assuming binomial sampling), some
      had more than others, implying a genetic basis. Using genetics and pharmacology,
      we identified the metabolite transporter White and white-dependent serotonin as
      suppressors of phototactic personality. Because we observed behavioral
      idiosyncrasy in all experimental groups, we suspect it is present in most
      behaviors of most animals.

PMID- 23150589
TI  - Hydroperiod regime controls the organization of plant species in wetlands.
AB  - With urban, agricultural, and industrial needs growing throughout the past
      decades, wetland ecosystems have experienced profound changes. Most critically,
      the biodiversity of wetlands is intimately linked to its hydrologic dynamics,
      which in turn are being drastically altered by ongoing climate changes.
      Hydroperiod regimes, e.g., percentage of time a site is inundated, exert critical
      control in the creation of niches for different plant species in wetlands.
      However, the spatial signatures of the organization of plant species in wetlands
      and how the different drivers interact to yield such signatures are unknown.
      Focusing on Everglades National Park (ENP) in Florida, we show here that cluster
      sizes of each species follow a power law probability distribution and that such
      clusters have well-defined fractal characteristics. Moreover, we individuate and
      model those signatures via the interplay between global forcings arising from the
      hydroperiod regime and local controls exerted by neighboring vegetation. With
      power law clustering often associated with systems near critical transitions, our
      findings are highly relevant for the management of wetland ecosystems. In
      addition, our results show that changes in climate and land management have a
      quantifiable predictable impact on the type of vegetation and its spatial
      organization in wetlands.

PMID- 23150590
TI  - McClintock's challenge in the 21st century.
AB  - In 1950, Barbara McClintock published a Classic PNAS article, "The origin and
      behavior of mutable loci in maize," which summarized the evidence leading to her
      discovery of transposition. The article described a number of genome alterations
      revealed through her studies of the Dissociation locus, the first mobile genetic
      element she identified. McClintock described the suite of nuclear events,
      including transposon activation and various chromosome aberrations and
      rearrangements, that unfolded in the wake of genetic crosses that brought
      together two broken chromosomes 9. McClintock left future generations with the
      challenge of understanding how genomes respond to genetic and environmental
      stresses by mounting adaptive responses that frequently include genome
      restructuring.

PMID- 23150591
TI  - Carbon and other light element contents in the Earth's core based on first
      principles molecular dynamics.
AB  - Carbon (C) is one of the candidate light elements proposed to account for the
      density deficit of the Earth's core. In addition, C significantly affects
      siderophile and chalcophile element partitioning between metal and silicate and
      thus the distribution of these elements in the Earth's core and mantle.
      Derivation of the accretion and core-mantle segregation history of the Earth
      requires, therefore, an accurate knowledge of the C abundance in the Earth's
      core. Previous estimates of the C content of the core differ by a factor of ~20
      due to differences in assumptions and methods, and because the metal-silicate
      partition coefficient of C was previously unknown. Here we use two-phase first
      principles molecular dynamics to derive this partition coefficient of C between
      liquid iron and silicate melt. We calculate a value of 9 +/- 3 at 3,200 K and 40
      GPa. Using this partition coefficient and the most recent estimates of bulk Earth
      or mantle C contents, we infer that the Earth's core contains 0.1-0.7 wt% of C.
      Carbon thus plays a moderate role in the density deficit of the core and in the
      distribution of siderophile and chalcophile elements during core-mantle
      segregation processes. The partition coefficients of nitrogen (N), hydrogen,
      helium, phosphorus, magnesium, oxygen, and silicon are also inferred and found to
      be in close agreement with experiments and other geochemical constraints.
      Contents of these elements in the core derived from applying these partition
      coefficients match those derived by using the cosmochemical volatility curve and
      geochemical mass balance arguments. N is an exception, indicating its retention
      in a mantle phase instead of in the core.

PMID- 23150592
TI  - More than one way to TRIM a capsid.

PMID- 23150594
TI  - alpha-Tubulin acetylation from the inside out.

PMID- 23150595
TI  - Entropy-enthalpy transduction caused by conformational shifts can obscure the
      forces driving protein-ligand binding.
AB  - Molecular dynamics simulations of unprecedented duration now can provide new
      insights into biomolecular mechanisms. Analysis of a 1-ms molecular dynamics
      simulation of the small protein bovine pancreatic trypsin inhibitor reveals that
      its main conformations have different thermodynamic profiles and that
      perturbation of a single geometric variable, such as a torsion angle or
      interresidue distance, can select for occupancy of one or another conformational
      state. These results establish the basis for a mechanism that we term entropy
      enthalpy transduction (EET), in which the thermodynamic character of a local
      perturbation, such as enthalpic binding of a small molecule, is camouflaged by
      the thermodynamics of a global conformational change induced by the perturbation,
      such as a switch into a high-entropy conformational state. It is noted that EET
      could occur in many systems, making measured entropies and enthalpies of folding
      and binding unreliable indicators of actual thermodynamic driving forces. The
      same mechanism might also account for the high experimental variance of measured
      enthalpies and entropies relative to free energies in some calorimetric studies.
      Finally, EET may be the physical mechanism underlying many cases of entropy
      enthalpy compensation.

PMID- 23150596
TI  - Sprouty genes function in suppression of prostate tumorigenesis.
AB  - Expression of Sprouty genes is frequently decreased or absent in human prostate
      cancer, implicating them as suppressors of tumorigenesis. Here we show they
      function in prostate tumor suppression in the mouse. Concomitant inactivation of
      Spry1 and Spry2 in prostate epithelium causes ductal hyperplasia and low-grade
      prostatic intraepithelial neoplasia (PIN). However, when Spry1 and Spry2 loss-of
      function occurs in the context of heterozygosity for a null allele of the tumor
      suppressor gene Pten, there is a striking increase in PIN and evidence of
      neoplastic invasion. Conversely, expression of a Spry2 gain-of-function transgene
      in Pten null prostatic epithelium suppresses the tumorigenic effects of loss of
      Pten function. We show that Sprouty gene loss-of-function results in hyperactive
      RAS/ERK1/2 signaling throughout the prostate epithelium and cooperates with
      heterozygosity for a Pten null allele to promote hyperactive PI3K/AKT signaling.
      Furthermore, Spry2 gain-of-function can suppress hyperactivation of AKT caused by
      the absence of PTEN. Together, these results point to a key genetic interaction
      between Sprouty genes and Pten in prostate tumorigenesis and provide strong
      evidence that Sprouty genes can function to modulate signaling via the RAS/ERK1/2
      and PI3K/AKT pathways. The finding that Sprouty genes suppress tumorigenesis
      caused by Pten loss-of-function suggests that therapeutic approaches aimed at
      restoring normal feedback mechanisms triggered by receptor tyrosine kinase
      signaling, including Sprouty gene expression, may provide an effective strategy
      to delay or prevent high-grade PIN and invasive prostate cancer.

PMID- 23150597
TI  - toca-1 is in a novel pathway that functions in parallel with a SUN-KASH nuclear
      envelope bridge to move nuclei in Caenorhabditis elegans.
AB  - Moving the nucleus to an intracellular location is critical to many fundamental
      cell and developmental processes, including cell migration, differentiation,
      fertilization, and establishment of cellular polarity. Bridges of SUN and KASH
      proteins span the nuclear envelope and mediate many nuclear positioning events,
      but other pathways function independently through poorly characterized
      mechanisms. To identify and characterize novel mechanisms of nuclear migration,
      we conducted a nonbiased forward genetic screen for mutations that enhanced the
      nuclear migration defect of unc-84, which encodes a SUN protein. In
      Caenorhabditis elegans larvae, failure of hypodermal P-cell nuclear migration
      results in uncoordinated and egg-laying-defective animals. The process of P-cell
      nuclear migration in unc-84 null animals is temperature sensitive; at 25 degrees 
      migration fails in unc-84 mutants, but at 15 degrees  the migration occurs
      normally. We hypothesized that an additional pathway functions in parallel to the
      unc-84 pathway to move P-cell nuclei at 15 degrees . In support of our
      hypothesis, forward genetic screens isolated eight emu (enhancer of the nuclear
      migration defect of unc-84) mutations that disrupt nuclear migration only in a
      null unc-84 background. The yc20 mutant was determined to carry a mutation in the
      toca-1 gene. TOCA-1 functions to move P-cell nuclei in a cell-autonomous manner.
      TOCA-1 is conserved in humans, where it functions to nucleate and organize actin
      during endocytosis. Therefore, we have uncovered a player in a previously
      unknown, likely actin-dependent, pathway that functions to move nuclei in
      parallel to SUN-KASH bridges. The other emu mutations potentially represent other
      components of this novel pathway.

PMID- 23150598
TI  - Defining the epigenetic mechanism of asymmetric cell division of
      Schizosaccharomyces japonicus yeast.
AB  - A key question in developmental biology addresses the mechanism of asymmetric
      cell division. Asymmetry is crucial for generating cellular diversity required
      for development in multicellular organisms. As one of the potential mechanisms,
      chromosomally borne epigenetic difference between sister cells that changes
      mating/cell type has been demonstrated only in the Schizosaccharomyces pombe
      fission yeast. For technical reasons, it is nearly impossible to determine the
      existence of such a mechanism operating during embryonic development of
      multicellular organisms. Our work addresses whether such an epigenetic mechanism
      causes asymmetric cell division in the recently sequenced fission yeast, S.
      japonicus (with 36% GC content), which is highly diverged from the well-studied
      S. pombe species (with 44% GC content). We find that the genomic location and DNA
      sequences of the mating-type loci of S. japonicus differ vastly from those of the
      S. pombe species. Remarkably however, similar to S. pombe, the S. japonicus cells
      switch cell/mating type after undergoing two consecutive cycles of asymmetric
      cell divisions: only one among four "granddaughter" cells switches. The DNA
      strand-specific epigenetic imprint at the mating-type locus1 initiates the
      recombination event, which is required for cellular differentiation. Therefore
      the S. pombe and S. japonicus mating systems provide the first two examples in
      which the intrinsic chirality of double helical structure of DNA forms the
      primary determinant of asymmetric cell division. Our results show that this
      unique strand-specific imprinting/segregation epigenetic mechanism for asymmetric
      cell division is evolutionary conserved. Motivated by these findings, we
      speculate that DNA-strand-specific epigenetic mechanisms might have evolved to
      dictate asymmetric cell division in diploid, higher eukaryotes as well.

PMID- 23150599
TI  - Genetic dissection of peroxisome-associated matrix protein degradation in
      Arabidopsis thaliana.
AB  - Peroxisomes are organelles that sequester certain metabolic pathways; many of
      these pathways generate H(2)O(2), which can damage proteins. However, little is
      known about how damaged or obsolete peroxisomal proteins are degraded. We exploit
      developmentally timed peroxisomal content remodeling in Arabidopsis thaliana to
      elucidate peroxisome-associated protein degradation. Isocitrate lyase (ICL) is a
      peroxisomal glyoxylate cycle enzyme necessary for early seedling development. A
      few days after germination, photosynthesis begins and ICL is degraded. We
      previously found that ICL is stabilized when a peroxisome-associated ubiquitin
      conjugating enzyme and its membrane anchor are both mutated, suggesting that
      matrix proteins might exit the peroxisome for ubiquitin-dependent cytosolic
      degradation. To identify additional components needed for peroxisome-associated
      matrix protein degradation, we mutagenized a line expressing GFP-ICL, which is
      degraded similarly to endogenous ICL, and identified persistent GFP-ICL
      fluorescence (pfl) mutants. We found three pfl mutants that were defective in
      PEROXIN14 (PEX14/At5g62810), which encodes a peroxisomal membrane protein that
      assists in importing proteins into the peroxisome matrix, indicating that
      proteins must enter the peroxisome for efficient degradation. One pfl mutant was
      missing the peroxisomal 3-ketoacyl-CoA thiolase encoded by the PEROXISOME
      DEFECTIVE1 (PED1/At2g33150) gene, suggesting that peroxisomal metabolism
      influences the rate of matrix protein degradation. Finally, one pfl mutant that
      displayed normal matrix protein import carried a novel lesion in PEROXIN6
      (PEX6/At1g03000), which encodes a peroxisome-tethered ATPase that is involved in
      recycling matrix protein receptors back to the cytosol. The isolation of pex6-2
      as a pfl mutant supports the hypothesis that matrix proteins can exit the
      peroxisome for cytosolic degradation.

PMID- 23150600
TI  - An ancestral recombination graph for diploid populations with skewed offspring
      distribution.
AB  - A large offspring-number diploid biparental multilocus population model of Moran
      type is our object of study. At each time step, a pair of diploid individuals
      drawn uniformly at random contributes offspring to the population. The number of
      offspring can be large relative to the total population size. Similar "heavily
      skewed" reproduction mechanisms have been recently considered by various authors
      (cf. e.g., Eldon and Wakeley 2006, 2008) and reviewed by Hedgecock and Pudovkin
      (2011). Each diploid parental individual contributes exactly one chromosome to
      each diploid offspring, and hence ancestral lineages can coalesce only when in
      distinct individuals. A separation-of-timescales phenomenon is thus observed. A
      result of Mohle (1998) is extended to obtain convergence of the ancestral process
      to an ancestral recombination graph necessarily admitting simultaneous multiple
      mergers of ancestral lineages. The usual ancestral recombination graph is
      obtained as a special case of our model when the parents contribute only one
      offspring to the population each time. Due to diploidy and large offspring
      numbers, novel effects appear. For example, the marginal genealogy at each locus
      admits simultaneous multiple mergers in up to four groups, and different loci
      remain substantially correlated even as the recombination rate grows large. Thus,
      genealogies for loci far apart on the same chromosome remain correlated.
      Correlation in coalescence times for two loci is derived and shown to be a
      function of the coalescence parameters of our model. Extending the observations
      by Eldon and Wakeley (2008), predictions of linkage disequilibrium are shown to
      be functions of the reproduction parameters of our model, in addition to the
      recombination rate. Correlations in ratios of coalescence times between loci can
      be high, even when the recombination rate is high and sample size is large, in
      large offspring-number populations, as suggested by simulations, hinting at how
      to distinguish between different population models.

PMID- 23150601
TI  - Long-range targeted manipulation of the Drosophila genome by site-specific
      integration and recombinational resolution.
AB  - Significant advances in genomics underscore the importance of targeted
      mutagenesis for gene function analysis. Here we have developed a scheme for long
      range targeted manipulation of genes in the Drosophila genome. Utilizing an attP
      attachment site for the phiC31 integrase previously targeted to the nbs gene, we
      integrated an 80-kb genomic fragment at its endogenous locus to generate a tandem
      duplication of the region. We achieved reduction to a single copy by inducing
      recombination via a site-specific DNA break. We report that, despite the large
      size of the DNA fragment, both plasmid integration and duplication reduction can
      be accomplished efficiently. Importantly, the integrating genomic fragment can
      serve as a venue for introducing targeted modifications to the entire region. We
      successfully introduced a new attachment site 70 kb from the existing attP using
      this two-step scheme, making a new region susceptible to targeted mutagenesis. By
      experimenting with different placements of the future DNA break site in the
      integrating vector, we established a vector configuration that facilitates the
      recovery of desired modifications. We also show that reduction events can occur
      efficiently through unequal meiotic crossing over between the large duplications.
      Based on our results, we suggest that a collection of 1200 lines with attachment
      sites inserted every 140 kb throughout the genome would render all Drosophila
      genes amenable to targeted mutagenesis. Excitingly, all of the components
      involved are likely functional in other eukaryotes, making our scheme for long
      range targeted manipulation readily applicable to other systems.

PMID- 23150602
TI  - The effect of genomic inversions on estimation of population genetic parameters
      from SNP data.
AB  - In recent years it has emerged that structural variants have a substantial impact
      on genomic variation. Inversion polymorphisms represent a significant class of
      structural variant, and despite the challenges in their detection, data on
      inversions in the human genome are increasing rapidly. Statistical methods for
      inferring parameters such as the recombination rate and the selection coefficient
      have generally been developed without accounting for the presence of inversions.
      Here we exploit new software for simulating inversions in population genetic
      data, invertFREGENE, to assess the potential impact of inversions on such
      methods. Using data simulated by invertFREGENE, as well as real data from several
      sources, we test whether large inversions have a disruptive effect on widely
      applied population genetics methods for inferring recombination rates, for
      detecting selection, and for controlling for population structure in genome-wide
      association studies (GWAS). We find that recombination rates estimated by LDhat
      are biased downward at inversion loci relative to the true contemporary
      recombination rates at the loci but that recombination hotspots are not falsely
      inferred at inversion breakpoints as may have been expected. We find that the
      integrated haplotype score (iHS) method for detecting selection appears robust to
      the presence of inversions. Finally, we observe a strong bias in the genome-wide
      results of principal components analysis (PCA), used to control for population
      structure in GWAS, in the presence of even a single large inversion, confirming
      the necessity to thin SNPs by linkage disequilibrium at large physical distances
      to obtain unbiased results.

PMID- 23150603
TI  - A mammalian-like DNA damage response of fission yeast to nucleoside analogs.
AB  - Nucleoside analogs are frequently used to label newly synthesized DNA. These
      analogs are toxic in many cells, with the exception of the budding yeast. We show
      that Schizosaccharomyces pombe behaves similarly to metazoans in response to
      analogs 5-bromo-2'-deoxyuridine (BrdU) and 5-ethynyl-2'-deoxyuridine (EdU).
      Incorporation causes DNA damage that activates the damage checkpoint kinase Chk1
      and sensitizes cells to UV light and other DNA-damaging drugs. Replication
      checkpoint mutant cds1Delta shows increased DNA damage response after exposure.
      Finally, we demonstrate that the response to BrdU is influenced by the
      ribonucleotide reductase inhibitor, Spd1, suggesting that BrdU causes dNTP pool
      imbalance in fission yeast, as in metazoans. Consistent with this, we show that
      excess thymidine induces G1 arrest in wild-type fission yeast expressing
      thymidine kinase. Thus, fission yeast responds to nucleoside analogs similarly to
      mammalian cells, which has implications for their use in replication and damage
      research, as well as for dNTP metabolism.

PMID- 23150604
TI  - Captured segment exchange: a strategy for custom engineering large genomic
      regions in Drosophila melanogaster.
AB  - Site-specific recombinases (SSRs) are valuable tools for manipulating genomes. In
      Drosophila, thousands of transgenic insertions carrying SSR recognition sites
      have been distributed throughout the genome by several large-scale projects. Here
      we describe a method with the potential to use these insertions to make custom
      alterations to the Drosophila genome in vivo. Specifically, by employing
      recombineering techniques and a dual recombinase-mediated cassette exchange
      strategy based on the phiC31 integrase and FLP recombinase, we show that a large
      genomic segment that lies between two SSR recognition-site insertions can be
      "captured" as a target cassette and exchanged for a sequence that was engineered
      in bacterial cells. We demonstrate this approach by targeting a 50-kb segment
      spanning the tsh gene, replacing the existing segment with corresponding
      recombineered sequences through simple and efficient manipulations. Given the
      high density of SSR recognition-site insertions in Drosophila, our method affords
      a straightforward and highly efficient approach to explore gene function in situ
      for a substantial portion of the Drosophila genome.

PMID- 23150605
TI  - Demographic inference reveals African and European admixture in the North
      American Drosophila melanogaster population.
AB  - Drosophila melanogaster spread from sub-Saharan Africa to the rest of the world
      colonizing new environments. Here, we modeled the joint demography of African
      (Zimbabwe), European (The Netherlands), and North American (North Carolina)
      populations using an approximate Bayesian computation (ABC) approach. By testing
      different models (including scenarios with continuous migration), we found that
      admixture between Africa and Europe most likely generated the North American
      population, with an estimated proportion of African ancestry of 15%. We also
      revisited the demography of the ancestral population (Africa) and found-in
      contrast to previous work-that a bottleneck fits the history of the population of
      Zimbabwe better than expansion. Finally, we compared the site-frequency spectrum
      of the ancestral population to analytical predictions under the estimated
      bottleneck model.

PMID- 23150606
TI  - Extensive divergence between mating-type chromosomes of the anther-smut fungus.
AB  - Genomic regions that determine mating compatibility are subject to distinct
      evolutionary forces that can lead to a cessation of meiotic recombination and the
      accumulation of structural changes between members of the homologous chromosome
      pair. The relatively recent discovery of dimorphic mating-type chromosomes in
      fungi can aid the understanding of sex chromosome evolution that is common to
      dioecious plants and animals. For the anther-smut fungus, Microbotryum lychnidis
      dioicae (= M. violaceum isolated from Silene latifolia), the extent of
      recombination cessation on the dimorphic mating-type chromosomes has been
      conflictingly reported. Comparison of restriction digest optical maps for the two
      mating-type chromosomes shows that divergence extends over 90% of the chromosome
      lengths, flanked at either end by two pseudoautosomal regions. Evidence to
      support the expansion of recombination cessation in stages from the mating-type
      locus toward the pseudoautosomal regions was not found, but evidence of such
      expansion could be obscured by ongoing processes that affect genome structure.
      This study encourages the comparison of forces that may drive large-scale
      recombination suppression in fungi and other eukaryotes characterized by
      dimorphic chromosome pairs associated with sexual life cycles.

PMID- 23150608
TI  - Resource use and cost implications of switching among warfarin formulations in
      atrial fibrillation patients.
AB  - BACKGROUND: Despite the uncertainty surrounding the safety of switching warfarin
      formulations, limited data exist on the resource use and costs associated with
      this switching pattern. OBJECTIVE: To evaluate health care resource use and costs
      associated with switching warfarin formulations among patients with atrial
      fibrillation (AF) in a managed care organization. METHODS: Patients diagnosed
      with AF (ICD-9 427.31) between July 2004 and August 2008 and who received
      warfarin therapy were identified in the HealthCore Integrated Research Database
      and categorized into 3 groups: users of generic warfarin formulations from a
      single drug manufacturer (generic-only group), users of branded warfarin
      formulations only (brand-only group), and patients who used generic and branded
      warfarin therapy interchangeably or who may have used generic drugs from 1 or
      more manufacturers (generic/brand switching group). Patients were followed 12
      months or longer after their index warfarin prescription date to compare all
      cause resource use and costs using multivariable regression analysis. RESULTS:
      The analysis included 12,908 patients: 71.82% were in the genericonly group,
      9.61% were in the brand-only group, and 18.57% were in the generic/brand
      switching group. Patients in the generic/brand switching group were more likely
      to be hospitalized (relative risk [RR] = 1.43, p < 0.0001) or to use emergency
      department services (RR = 1.20, p < 0.01), compared to the brand-only users.
      Hospitalizations were more likely (RR = 1.26, p < 0.001) to occur among generic
      only users versus brand-only users. Adjusted mean pharmacy costs per member per
      month were lower in the generic/brand switching group compared to the brand-only
      group ($257 vs $273, p = 0.038), but inpatient costs were higher ($1250 vs $972,
      p < 0.001), resulting in higher ($2125 vs $1847, p < 0.001) total costs. Generic
      only users had lower pharmacy costs compared to brand-only users ($246 vs $273, p
      < 0.001), but total health care costs trended to be higher in the generic-only
      group ($1957 vs $1847, p = 0.053). CONCLUSIONS: The use of both generic and
      branded formulations of warfarin interchangeably, or the use of generics from
      more than 1 manufacturer, was associated with increased use of all-cause health
      care resources and total costs in patients with AF.

PMID- 23150607
TI  - Genetic variants contribute to gene expression variability in humans.
AB  - Expression quantitative trait loci (eQTL) studies have established convincing
      relationships between genetic variants and gene expression. Most of these studies
      focused on the mean of gene expression level, but not the variance of gene
      expression level (i.e., gene expression variability). In the present study, we
      systematically explore genome-wide association between genetic variants and gene
      expression variability in humans. We adapt the double generalized linear model
      (dglm) to simultaneously fit the means and the variances of gene expression among
      the three possible genotypes of a biallelic SNP. The genomic loci showing
      significant association between the variances of gene expression and the
      genotypes are termed expression variability QTL (evQTL). Using a data set of gene
      expression in lymphoblastoid cell lines (LCLs) derived from 210 HapMap
      individuals, we identify cis-acting evQTL involving 218 distinct genes, among
      which 8 genes, ADCY1, CTNNA2, DAAM2, FERMT2, IL6, PLOD2, SNX7, and TNFRSF11B, are
      cross-validated using an extra expression data set of the same LCLs. We also
      identify ~300 trans-acting evQTL between >13,000 common SNPs and 500 randomly
      selected representative genes. We employ two distinct scenarios, emphasizing
      single-SNP and multiple-SNP effects on expression variability, to explain the
      formation of evQTL. We argue that detecting evQTL may represent a novel method
      for effectively screening for genetic interactions, especially when the multiple
      SNP influence on expression variability is implied. The implication of our
      results for revealing genetic mechanisms of gene expression variability is
      discussed.

PMID- 23150609
TI  - Suboptimal access to primary healthcare among street-based sex workers in
      southwest Switzerland.
AB  - OBJECTIVES: Street-based sex workers (SSWs) in Lausanne, Switzerland, are poorly
      characterised. We set out to quantify potential vulnerability factors in this
      population and to examine SSW healthcare use and unmet healthcare requirements.
      METHODS: We conducted a cross-sectional questionnaire-based survey among SSWs
      working in Lausanne's red light district between 1 February and 31 July 2010,
      examining SSW socio-demographic characteristics and factors related to their
      healthcare. RESULTS: We interviewed 50 SSWs (76% of those approached). A fifth
      conducted their interviews in French, the official language in Lausanne. 48
      participants (96%) were migrants, of whom 33/48 (69%) held no residence permit.
      22/50 (44%) had been educated beyond obligatory schooling. 28/50 (56%) had no
      health insurance. 18/50 (36%) had been victims of physical violence. While 36/50
      (72%) had seen a doctor during the preceding 12 months, only 15/50 (30%) were
      aware of a free clinic for individuals without health insurance. Those unaware of
      free services consulted emergency departments or doctors outside Switzerland.
      Gynaecology, primary healthcare and dental services were most often listed as
      needed. Two individuals (of 50, 4%) disclosed positive HIV status; of the others,
      24/48 (50%) had never had an HIV test. CONCLUSIONS: This vulnerable population
      comprises SSWs who, whether through mobility, insufficient education or language
      barriers, are unaware of services they are entitled to. With half the
      participants reporting no HIV testing, there is a need to enhance awareness of
      available facilities as well as to increase provision and uptake of HIV testing.

PMID- 23150610
TI  - Cell penetration peptides for enhanced entry of alphaB-crystallin into lens
      cells.
AB  - PURPOSE: The prevalence of cataract increases with age. Conversely, the abundance
      of native alpha-crystallin diminishes with age and cataract development. We
      hypothesize replenishing lens alpha-crystallin may delay or prevent cataract.
      Herein we investigated the ability of cell penetration peptides (CPP) to enhance
      entry of alpha-crystallins into lens-derived cells. METHODS: Recombinant alphaB
      crystallins were modified by the addition of CPPs. Candidate CPP were designed
      with reference to the HSV-1 glycoprotein C gene (gC) or the HIV-1 TAT peptide.
      alphaB-crystallins produced by fusing gC or TAT were over-expressed in E. coli.
      Purified proteins were subjected to size exclusion chromatography (SEC) to
      characterize oligomeric complexes (OC). Chaperone-like activity (CLA) was
      evaluated by measuring the ability of alpha-crystallins to suppress chemically
      induced protein aggregation. To evaluate protein uptake, labeled alpha
      crystallins were incubated with HLE B3 cells and monitored by fluorescence
      microscopy for 48 hours. RESULTS: We examined the effects of the addition of CPP
      on the structure, CLA, and cell transduction properties of alphaB-crystallins. C
      terminal CPP fused crystallins had poor solubility. In contrast, N-terminal
      tagged alphaB-crystallins were soluble. These modified alphaB-crystallins formed
      OC that were larger than wild-type based on SEC. Wild-type and gC tagged alphaB
      crystallin displayed robust CLA. Subunit exchange was observed when gC-fused
      alphaB-crystallin was mixed with alphaA. In contrast to wild-type, modified alpha
      crystallins accumulated in HLE B3 cells. CONCLUSIONS: Addition of CPP improves
      the uptake of alphaB-crystallins into HLE B3 cells. No undesirable changes to the
      chaperone-like abilities of alpha-crystallins were observed in alphaB-crystallin
      modified by the addition of the gC-derived CPP.

PMID- 23150611
TI  - The relationship between growth spurts and myopia in Singapore children.
AB  - PURPOSE: We aimed to determine the relationship between puberty and growth spurts
      with peak spherical equivalent (SE) or axial length (AL) velocity in Singapore
      schoolchildren. METHODS: In the Singapore Cohort Study of the Risk Factors for
      Myopia of 1779 schoolchildren, the longitudinal refractive and pubertal status of
      892 boys and 887 girls from ages 6 to 14 years were assessed. The study sample
      included 1329 Chinese, 316 Malays, 114 Indians, and 20 children of other races.
      Information regarding puberty parameters, age of peak height velocity, age of
      menarche, and break of voice (BOV) was obtained. Peak velocity was defined as the
      greatest change in measurements over a period of 1 year. Tanner stage 1 for pubic
      hair or breast development, in boys and girls, respectively, at age 12 was
      categorized as "later puberty," whereas stages 2 to 5 corresponded to "earlier
      puberty." Refractive error was determined by cycloplegic autorefraction using the
      Canon RK-F5, and AL was measured using the A-scan biometry machine. RESULTS: The
      children were examined annually, and the mean number of visits was 5.7 +/- 1.3.
      Age of peak height velocity occurred earlier in girls than in boys (11.0 +/- 1.2
      vs. 12.0 +/- 1.7 years, P < 0.001). Girls with earlier peak height velocity
      experienced peak AL velocity and peak SE velocity approximately half a year
      earlier than those with later puberty (mean age of 10.3 +/- 1.6 vs. 10.8 +/- 1.7
      years, P < 0.001; and 10.0 +/- 1.5 vs. 10.6 +/- 1.25 years, P < 0.001,
      respectively). Similarly, boys who had earlier peak height velocity also achieved
      peak AL and peak SE velocity earlier than those who experienced later peak height
      velocity (mean age of 10.4 +/- 1.6 vs. 11.1 +/- 1.8 years, P < 0.001; and 10.1 +/
      1.5 vs. 10.6 +/- 1.7 years, P = 0.01). Both girls and boys who had early peak
      height velocity had earlier age of onset of myopia than those with later peak
      height velocity (9.7 +/- 1.4 vs. 10.1 +/- 1.5 years for girls, P = 0.04; and 9.9
      +/- 1.5 vs. 10.4 +/- 1.6 years for boys, P = 0.03). Myopia progression, in terms
      of AL velocity, also occurred earlier in boys and girls with earlier peak height
      velocity (10.2 +/- 1.5 vs. 11.0 +/- 1.9 for boys, P < 0.001; and 10.2 +/- 1.5 vs.
      10.7 +/- 1.7 for girls, P = 0.004, respectively). The associations were not
      significant when Tanner staging, age of menarche, or BOV was used to determine
      stage of puberty. CONCLUSIONS: Boys and girls with earlier peak height velocity
      experienced earlier peak SE and AL velocity, and age of myopia onset. Thus,
      variations in the onset and peak progression of myopia may be associated with
      height spurts.

PMID- 23150612
TI  - Mutations in RPGR and RP2 account for 15% of males with simplex retinal
      degenerative disease.
AB  - PURPOSE: To determine the proportion of male patients presenting simplex retinal
      degenerative disease (RD: retinitis pigmentosa [RP] or cone/cone-rod dystrophy
      [COD/CORD]) with mutations in the X-linked retinal degeneration genes RPGR and
      RP2. METHODS: Simplex males were defined as patients with no known affected
      family members. Patients were excluded if they had a family history of parental
      consanguinity. Blood samples from a total of 214 simplex males with a diagnosis
      of retinal degeneration were collected for genetic analysis. The patients were
      screened for mutations in RPGR and RP2 by direct sequencing of PCR-amplified
      genomic DNA. RESULTS: We identified pathogenic mutations in 32 of the 214
      patients screened (15%). Of the 29 patients with a diagnosis of COD/CORD, four
      mutations were identified in the ORF15 mutational hotspot of the RPGR gene. Of
      the 185 RP patients, three patients had mutations in RP2 and 25 had RPGR
      mutations (including 12 in the ORF15 region). CONCLUSIONS: This study represents
      mutation screening of RPGR and RP2 in the largest cohort, to date, of simplex
      males affected with RP or COD/CORD. Our results demonstrate a substantial
      contribution of RPGR mutations to retinal degenerations, and in particular, to
      simplex RP. Based on our findings, we suggest that RPGR should be considered as a
      first tier gene for screening isolated males with retinal degeneration.

PMID- 23150613
TI  - Vascular Endothelial Growth Factor Receptor 1 morpholino increases graft survival
      in a murine penetrating keratoplasty model.
AB  - PURPOSE: This study sought to determine whether a Vascular Endothelial Growth
      Factor Receptor 1 (VEGFR1)-specific morpholino (MO) could decrease
      neovascularization, thereby enhancing murine cornea transplant survival, and if
      this effect is synergistic with steroid therapy. METHODS: Graft survival, corneal
      neovascularization, and corneal lymphangiogenesis were compared among the
      VEGFR1_MO, STD MO and PBS groups following subconjunctival injection in mice that
      underwent normal risk penetrating keratoplasty (NR PK) and high-risk penetrating
      keratoplasty (HR PK). Graft survival, corneal neovascularization, and corneal
      lymphangiogenesis in groups treated with both VEGFR1_MO and steroid therapy were
      also analyzed in HR PK. RESULTS: In NR PK, the VEGFR1_MO decreased angiogenesis,
      lymphangiogenesis, and increased graft survival compared with the PBS group (P =
      0.055, P = 0.003, P = 0.043, respectively). In HR PK, VEGFR1_MO decreased
      angiogenesis, lymphangiogenesis, and increased graft survival compared with the
      STD MO (P = 0.000, P = 0.000, P = 0.029, respectively) and PBS groups (P = 0.004,
      P = 0.002, P = 0.024). In HR PK, when the VEGFR1_MO was combined with steroid
      therapy, a significant increase in graft survival was seen compared with steroid
      treatment alone (P = 0.045). The 2-month graft survival rate for HR PK was 27% in
      the combination group compared with 0% in the triamcinolone only group.
      CONCLUSIONS: VEGFR1_MO decreased angiogenesis and lymphangiogenesis, resulting in
      increased graft survival in both NR PK and HR PK. This beneficial effect is
      synergistically enhanced with steroid treatment in HR PK.

PMID- 23150614
TI  - An ENU mutagenesis screen in zebrafish for visual system mutants identifies a
      novel splice-acceptor site mutation in patched2 that results in Colobomas.
AB  - PURPOSE: To identify recessive mutations affecting development and/or maintenance
      of the zebrafish visual system. METHODS: A three-generation ENU (N-Nitroso-N
      ethylurea)-based forward genetic screen was performed. F3 embryos were screened
      visually from 1 to 5 days postfertilization (dpf) for ocular abnormalities, and 5
      dpf embryos were fixed and processed for cryosectioning, after which eye sections
      were screened for defects in cellular organization within the retina, lens, and
      cornea. A combination of PCR and DNA sequencing, in situ hybridization, and
      pharmacological treatments were used to clone and characterize a coloboma mutant.
      RESULTS: A total of 126 F2 families were screened, and, from these, 18 recessive
      mutations were identified that affected eye development. Phenotypes included lens
      malformations and cataracts, photoreceptor defects, oculocutaneous albinism,
      microphthalmia, and colobomas. Analysis of one such coloboma mutant, uta(1),
      identified a splice-acceptor mutation in the patched2 gene that resulted in an in
      frame deletion of 19 amino acids that are predicted to contribute to the first
      extracellular loop of Patched2. ptch2(uta1) mutants possessed elevated Hedgehog
      (Hh) pathway activity, and blocking the Hh pathway with cyclopamine prevented
      colobomas in ptch2(uta1) mutant embryos. CONCLUSIONS: We have identified 18
      recessive mutations affecting development of the zebrafish visual system and we
      have characterized a novel splice-acceptor site mutation in patched2 that results
      in enhanced Hh pathway activity and colobomas.

PMID- 23150615
TI  - Evaluation of lipid oxidative stress status in Sjogren syndrome patients.
AB  - PURPOSE: We evaluated the levels of lipid oxidative stress markers and
      inflammatory cells from tears and conjunctiva of patients with Sjogren syndrome
      (SS) and normal subjects. METHODS: We examined 31 eyes of 16 patients (16
      females) with SS and 15 eyes of 10 healthy controls (2 males and 8 females) in
      this prospective study. All subjects underwent a Schirmer test, measurement of
      tear film break-up time, vital stainings, confocal microscopy of the conjunctiva,
      tear collection for hexanoyl-lysine (HEL), ELISA, and conjunctival brush
      cytology. Brush cytology samples underwent immunohistochemistry (IHC) staining
      with HEL and 4-hydroxy-2-nonenal (4HNE). Hematoxylin-eosin and IHC staining with
      HEL and 4HNE also were performed on conjunctival samples of SS patients and
      controls. RESULTS: The tear stability and vital staining scores were
      significantly worse in eyes of SS patients compared to the controls. Conjunctival
      inflammatory cell density was significantly higher in SS subjects compared to
      controls. The numbers of conjunctival cells stained positively for HEL and 4HNE
      were significantly higher in SS patients compared to controls. Tear HEL
      concentrations correlated significantly with staining scores and inflammatory
      cell density in confocal microscopy. Conjunctival specimens also revealed higher
      numbers of cells stained positively for inflammatory markers, as well as HEL and
      4HNE in the IHC stainings. CONCLUSIONS: Increase of the oxidative stress status
      in the conjunctiva of SS patients appears to have a role in the pathogenesis of
      dry eye disease. A close relationship may exist between reactive oxygen species
      (ROS) production, lipid peroxidation related membrane damage, and inflammatory
      processes in dry eye.

PMID- 23150616
TI  - In vivo confocal intrinsic optical signal identification of localized retinal
      dysfunction.
AB  - PURPOSE: The purposes of this study were to investigate the physiological
      mechanism of stimulus-evoked fast intrinsic optical signals (IOSs) recorded in
      dynamic confocal imaging of the retina, and to demonstrate the feasibility of in
      vivo confocal IOS mapping of localized retinal dysfunctions. METHODS: A rapid
      line-scan confocal ophthalmoscope was constructed to achieve in vivo confocal IOS
      imaging of frog (Rana pipiens) retinas at cellular resolution. In order to
      investigate the physiological mechanism of confocal IOS, comparative IOS and
      electroretinography (ERG) measurements were made using normal frog eyes activated
      by variable-intensity stimuli. A dynamic spatiotemporal filtering algorithm was
      developed to reject the contamination of hemodynamic changes on fast IOS
      recording. Laser-injured frog eyes were employed to test the potential of
      confocal IOS mapping of localized retinal dysfunctions. RESULTS: Comparative IOS
      and ERG experiments revealed a close correlation between the confocal IOS and
      retinal ERG, particularly the ERG a-wave, which has been widely used to evaluate
      photoreceptor function. IOS imaging of laser-injured frog eyes indicated that the
      confocal IOS could unambiguously detect localized (30 MUm) functional lesions in
      the retina before a morphological abnormality is detectable. CONCLUSIONS: The
      confocal IOS predominantly results from retinal photoreceptors, and can be used
      to map localized photoreceptor lesion in laser-injured frog eyes. We anticipate
      that confocal IOS imaging can provide applications in early detection of age
      related macular degeneration, retinitis pigmentosa, and other retinal diseases
      that can cause pathological changes in the photoreceptors.

PMID- 23150617
TI  - Sphingosine 1-phosphate elicits proinflammatory responses in ARPE-19 cells.
AB  - PURPOSE: To investigate the effects of sphingosine 1-phosphate (S1P) on the
      production of inflammatory mediators and the signaling pathways involved in S1P
      mediated production of cytokines by ARPE-19 cells. METHODS: Expression of S1P
      receptors was examined using RT-PCR and real-time PCR. ARPE-19 cells were
      stimulated with S1P or TNF-alpha, and by coculturing with S1P in the presence or
      absence of pertussis toxin (PTX) or a series of kinase inhibitors. The induction
      of inflammatory cytokine production was determined by ELISA. Western blot
      analysis was used to detect the activation of signaling mediators and S1P(3)
      receptor. RESULTS: ARPE-19 cells express all the known receptors for S1P.
      Moreover, exogenously applied S1P induces ARPE-19 cell secretion of interleukin-8
      (IL-8) in a dose- and time-dependent manner, but not IL-6 and monocyte
      chemotactic protein-1 (MCP-1). S1P-mediated IL-8 secretion is regulated by PTX,
      extracellular regulated protein kinases 1/2 (ERK1/2), and p38 mitogen-activated
      protein kinase (MAPK). Interestingly, treatment of ARPE-19 cells with TNF-alpha
      increases S1P(3) expression and correlates with the enhancement of S1P-induced IL
      8 and IL-6 production. CONCLUSIONS: This study demonstrates that S1P
      significantly promoted ARPE-19 cells to secrete inflammatory mediators.
      extracellular regulated protein kinases 1/2 (ERK1/2), p38 MAPK, and G(i)
      dependent pathways are important signaling components in S1P-mediated IL-8
      secretion by ARPE-19 cells. Moreover, these results provide evidence that S1P
      stimulation of RPE cells may play a role in regulating leukocyte function during
      ocular inflammation.

PMID- 23150618
TI  - Chemokine expression in retinal pigment epithelial ARPE-19 cells in response to
      coculture with activated T cells.
AB  - PURPOSE: To investigate the effects of T-cell-derived cytokines on gene and
      protein expression of chemokines in a human RPE cell line (ARPE-19). METHODS: We
      used an in vitro coculture system in which the RPE and CD3/CD28-activated T-cells
      were separated by a membrane. RPE cell expression of chemokine genes was
      quantified using three different types of microarrays. Protein expression was
      determined by single and multiplex ELISA and immunoblotting. RESULTS: Coculture
      with activated T-cells increased RPE mRNA and protein expression of chemokines
      CCL2 (MCP-1); CCL5 (RANTES); CCL7 (MCP-3); CCL8 (MCP-2); CXCL1 (GRO-alpha); IL8
      (CXCL8); CXCL9 (MIG); CXCL10 (IP10); CXCL11 (ITAC); and CX3CL1 (fractalkine).
      CCL7, CXCL9, CXCL10, and CXCL11 were secreted significantly more in the apical
      direction. Using recombinant human cytokines and neutralizing antibodies, we
      identified IFNgamma and TNFalpha as the two major T-cell-derived cytokines
      responsible for the RPE response. For CCL5, CXCL9, CXCL10, CXCL11, CXCL16, and
      CX3CL1, we observed a synergistic effect of IFNgamma and TNFalpha in combination.
      CCL20, CXCL1, CXCL6, and IL8 were negatively regulated by IFNgamma. CONCLUSIONS:
      RPE cells responded to exposure to T-cell-derived cytokines by upregulating
      expression of multiple chemokines related to microglial, T-cell, and monocyte
      chemotaxis and activation. This inflammatory stress response may have
      implications for immune homeostasis in the retina, and for the further
      understanding of inflammatory ocular diseases such as uveitis and AMD.

PMID- 23150619
TI  - Pharmacokinetics of ocriplasmin in vitreous.
AB  - PURPOSE: Ocriplasmin contains the active moiety of plasmin enzyme. At a
      physiologic pH, ocriplasmin is highly proteolytic and autolytic, limiting its
      duration of activity. Specific inhibitors of plasmin are present in the vitreous
      under normal and disease conditions and could affect its activity. Each may
      contribute to its mode of action. METHODS: Degradation characteristics were
      determined in porcine, human vitreous, and PBS under reducing conditions with
      different incubation periods between 0 and 24 hours on SDS-PAGE Tris-glycine
      gels. Residual activity was determined by spectrophotometry of p-nitroaniline
      release through hydrolysis of L-pyroglutamyl-L-phenylalanyl-L-lysine-p
      nitroaniline hydrochloride. The presence of endogenous inactivators of
      ocriplasmin in human vitreous was determined in a series of vitreous samples
      using an ELISA specific for alpha(2)-antiplasmin, antithrombin, and antitrypsin.
      RESULTS: Degradation productions from autolysis are similar between vitreous and
      PBS with a significant prolongation of the effect in vitreous. Both follow a
      nonlinear pattern over time. The degradation corresponds best to a second-order
      kinetic process. The resulting rate constants were 207 +/- 60 M(-1) s(-1) in PBS,
      81 +/- 15 M(-1) s(-1) in porcine vitreous, and 195 M(-1) s(-1) in human vitreous
      natural inhibitors were identified in samples of donor vitreous. Amounts differed
      significantly between samples, which may help explain the observed variability in
      human subjects. CONCLUSIONS: Ocriplasmin is autolytic in vitreous. Biologic
      activity extends to several days following injection. The exact duration will
      vary based on the presence and concentration of serine protease inhibitors.

PMID- 23150620
TI  - In vitro and in vivo comparative toxicological study of a new preservative-free
      latanoprost formulation.
AB  - PURPOSE: To compare in vitro, on the human reconstituted corneal epithelial
      SkinEthics model, and in vivo, using an acute rabbit toxicological model, the
      effects of a benzalkonium chloride (BAK)-preserved solution of latanoprost and a
      preservative-free (PF) latanoprost solution. METHODS: In vitro, the three
      dimensional (3D) reconstituted human corneal epithelia (HCE) were treated with
      PBS, BAK-latanoprost, PF-latanoprost, or 0.02% BAK for 24 hours followed or not
      followed by a 24 hour post incubation recovery period. Cellular viability was
      evaluated using the 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide
      (MTT) test at 24 hours and the apoptotic cells were counted using TUNEL labeling
      on frozen sections at 24 hours and 24 hours plus 24 hours. In vivo, rabbits
      received 50 MUL of the same solutions, which were applied at 5 minute intervals a
      total of 15 times. Ocular surface toxicity was investigated using slit lamp
      biomicroscopy examination, conjunctival impression cytology (CIC), and corneal in
      vivo confocal microscopy (IVCM). Standard immunohistology also assessed
      inflammatory CD45-positive cells. RESULTS: In vitro, BAK-latanoprost and 0.02%
      BAK induced significant apoptosis in the apical layers that correlated with the
      significant decrease of cell viability as assessed by the MTT test. PF
      latanoprost slightly decreased cell viability and few apoptotic cells were found
      in the superficial layers, without reaching statistical significance compared
      with PBS. In vivo, clinical observation and IVCM images showed the lowest ocular
      surface toxicity with PBS and PF-latanoprost, while BAK-latanoprost and BAK
      induced abnormal corneoconjunctival aspects. PF-latanoprost showed the lowest CIC
      score, close to the PBS score and induced fewer CD45-positive cells in both the
      limbus and the conjunctiva compared with BAK and latanoprost, as assessed by
      immunohistology. CONCLUSIONS: We confirm that rabbit corneoconjunctival surfaces
      presented better tolerance when treated with PF-latanoprost compared with the
      standard BAK-latanoprost preparation or the BAK solution.

PMID- 23150621
TI  - Postural control in nonamblyopic children with early-onset strabismus.
AB  - PURPOSE: In healthy subjects, the postural stability in orthostatic position is
      better when fixating at near than at far. Increase in the convergence angle
      contributes to this effect. Children with strabismus present a deficit in
      vergence. We evaluated postural control in children with respect to the vergence
      angle as they fixated at different depths, thereby engaging in active vergence
      movements. METHODS: A TechnoConcept platform was used to record the postural
      stability of 11 subjects (mean age 11.18 +/- 4.02 years) with convergent
      strabismus and 13 (mean age 11.31 +/- 3.54 years) with divergent strabismus in 3
      conditions: fixation at 40 cm, at 2 m, and active vergence movements between 20
      and 50 cm. RESULTS: The mediolateral body sway decreased significantly with
      proximity for convergent strabismus (from 3.78-2.70 mm) but increased
      significantly for divergent strabismus (from 3.27-3.97). Relative to fixation,
      vergence eye movements resulted in a statistically significant increase in
      mediolateral body sway for convergent strabismus (3.55 vs. 2.70) and a decrease
      for divergent strabismus (3.11 vs. 3.97, P = 0.047). Vergence eye movements were
      associated with the least variance of speed (99 mm(2)/s(2) for convergent and 117
      mm(2)/s(2) for divergent strabismus), so less energy was required to control body
      sway. CONCLUSIONS: The fixation depth at which postural stability is best is
      proximal for convergent strabismus and distal for divergent strabismus. Optimal
      postural stability might be mediated by preponderant eye movement signals related
      to the angle of strabismus. Reduction of variance of speed in the active vergence
      condition corroborates our hypothesis.

PMID- 23150622
TI  - The bioelectric field of the pattern electroretinogram in the mouse.
AB  - PURPOSE: To compare the bioelectric field associated with the pattern
      electroretinogram (PERG) with that of the flash electroretinogram (FERG) in the
      mouse. METHODS: PERGs and FERGs were recorded from each eye in 32 C57BL/6J mice
      using corneal silver loops referenced to a subcutaneous needle on the back of the
      head. PERG stimuli were horizontal gratings of 0.05 cycles per degree and 98%
      contrast reversing 2 times per second. Light-adapted FERG stimuli were bright
      strobe flashes. Stimuli were presented either monocularly or binocularly. In some
      experiments, TTX was injected in one eye and saline in the contralateral eye.
      RESULTS: The PERG recorded from the contralateral, occluded eye had slightly
      larger amplitude (1.14 *, P < 0.01) and longer latency (+1.57 ms, P < 0.01)
      compared with the ipsilateral eye. Under binocular stimulation, the PERG
      amplitude was much larger (1.67 *, P < 0.01) than the monocular amplitude. TTX
      injected in the stimulated eye drastically reduced the PERG in both eyes.
      Monocular FERGs were recordable from the stimulated eye only and were moderately
      reduced by TTX. Binocular and monocular FERGs had similar amplitudes.
      CONCLUSIONS: PERG and FERG generate different bioelectric fields in the mouse.
      The PERG bioelectric field is consistent with a dipole model whose axis is
      orthogonal to the eye axis, whereas the standard dipole model for the FERG is
      coaxial. Possible sources of the PERG bioelectric field are unmyelinated optic
      nerve axons adjacent to the sclera. Results provide new insights on the
      generators of the PERG signal and its alterations in mouse models of glaucoma and
      optic nerve diseases.

PMID- 23150623
TI  - Silica hybrid for corneal replacement: optical, biomechanical, and ex vivo
      biocompatibility studies.
AB  - PURPOSE: To investigate compositions of silica-collagen hybrid materials as
      potential artificial corneal substitutes, how these components affect the optical
      and biomechanical properties of the hybrids, and their biocompatibility in an
      organ culture model. METHODS: Hybrid materials were created from different
      proportions of collagen and silica precursors and manufactured to specific
      dimensions. The microstructure of the materials was determined by electron
      microscopy and mechanical strength was measured by using suture pullout tests.
      The refractive index and transmittance were measured by using an Abbe
      refractometer and a spectrophotometer. Materials were implanted into rabbit
      corneas to determine their epithelialization in organ culture. RESULTS: Scanning
      electron microscopy demonstrated that the hybrid material consisted of silica
      encapsulating collagen fibrils. The refractive index ranged from 1.332 to 1.403
      depending upon the composition and manufacturing characteristics. The rupture
      strength of a 3:1 (silica:collagen ratio by weight) rehydrated xerogel was 0.161
      +/- 0.073 N/mm (n = 12), while the hydrogels and 9:1 xerogel were too fragile for
      suturing. Re-epithelialization of 5- to 6-mm-wide rabbit corneal epithelial
      defects was complete in 5.5 +/- 2.4 days (n = 6), with evidence of epithelial
      stratification. CONCLUSIONS: Silica-collagen hybrid materials can be manufactured
      to specific dimensions to serve as a possible artificial corneal substitute. In
      preliminary studies, the materials had favorable optical, biomechanical, and
      biocompatibility properties necessary for replacing the corneal stroma.

PMID- 23150624
TI  - Automated "disease/no disease" grading of age-related macular degeneration by an
      image mining approach.
AB  - PURPOSE: To describe and evaluate an automated grading system for age-related
      macular degeneration (AMD) by color fundus photography. METHODS: An automated
      "disease/no disease" grading system for AMD was developed based on image-mining
      techniques. First, image preprocessing was performed to normalize color and
      nonuniform illumination of the fundus images to define a region of interest and
      to identify and remove pixels belonging to retinal vessels. To represent images
      for the prediction task, a graph-based image representation using quadtrees was
      then adopted. Next, a graph-mining technique was applied to the generated graphs
      to extract relevant features (in the form of frequent subgraphs) from images of
      both AMD and healthy volunteers. Features of the training data were then fed into
      a classifier generator for training purposes before employing the trained
      classifiers to classify new "unseen" images. RESULTS: The algorithm was evaluated
      on two publically available fundus-image datasets comprising 258 images (160 AMD
      and 98 normal). Ten-fold cross validation was used. The experiments produced a
      best specificity of 100% and a best sensitivity of 99.4% with an overall accuracy
      of 99.6%. Our approach outperformed previous approaches reported in the
      literature. CONCLUSIONS: This study has demonstrated a proof-of-concept, image
      mining technique for automated AMD grading. This technique has the potential to
      be further developed as an automated grading tool for future whole-scale AMD
      screening programs.

PMID- 23150625
TI  - Regulation of vascular endothelial growth factor expression by extra domain B
      segment of fibronectin in endothelial cells.
AB  - PURPOSE: Diabetic retinopathy entails proliferation of vascular endothelial cells
      (ECs) and unregulated angiogenesis. We have previously shown that ECs increase
      the expression of an embryonic variant of fibronectin (FN), called extra domain-B
      FN (ED-B FN) in response to high glucose. We also showed that ED-B FN regulates
      EC tube morphogenesis, possibly through vascular endothelial growth factor
      (VEGF). In the present study, we have attempted to decipher the mechanisms by
      which ED-B FN may modulate EC phenotype. METHODS: We hypothesized that ED-B FN
      regulates VEGF expression in ECs through interaction with selected integrin
      receptors. To test this hypothesis, we first cultured ECs in high levels of
      glucose to investigate for any alteration. We then used integrin-specific matrix
      mimetic peptides, neutralizing antibodies, and RNAi to identify the integrin(s)
      involved in VEGF expression. Finally, we used an animal model of diabetes to
      study whether these in vitro mechanisms also take place in the retina. RESULTS:
      Our results show that exposure of ECs to high levels of glucose increased VEGF
      expression. ED-B FN mediated this increase since knockdown of ED-B FN completely
      prevented glucose-induced VEGF expression. We then identified beta1 integrin as
      the essential receptor involved in high glucose-induced VEGF expression. We also
      showed that diabetes increased beta1 integrin and VEGF expression in the retina,
      which normalized upon ED-B knockdown. CONCLUSIONS: These findings showed that
      high levels of glucose in diabetes increased VEGF expression in ECs through ED-B
      FN and beta1 integrin interaction. These results provide novel mechanistic basis
      of increased VEGF expression in diabetes.

PMID- 23150626
TI  - Topical treatment with a new matrix therapy agent (RGTA) for the treatment of
      corneal neurotrophic ulcers.
AB  - PURPOSE: Neurotrophic keratopathy is a degenerative disease of the corneal
      epithelium resulting from impaired corneal innervation, possibly leading to
      perforation. We aimed to assess the efficacy and tolerance of a new matrix
      therapy agent (RGTA, Cacicol20), mimicking heparan sulfates, for the management
      of neurotrophic keratopathy. METHODS: We carried out an uncontrolled,
      prospective, single-center clinical study on 11 patients (11 eyes) with severe
      corneal neurotrophic ulcers, despite the use of preservative-free artificial
      tears, for 15 days. Patients were treated with RGTA eye drops, instilled at a
      dosage of one drop in the morning, on alternate days. Evolution and follow-up
      during treatment were evaluated by slit-lamp examination, photography,
      fluorescein-dye testing, tests of corneal sensitivity, and best corrected visual
      acuity. The main outcome measures for each patient were healing of the corneal
      surface and best corrected visual acuity before and after RGTA therapy. RESULTS:
      Eight patients displayed complete corneal healing after a mean period of 8.7
      weeks (range; 1 to 22 weeks). Mean ulcer area decreased significantly, from
      11.12% to 6.37% (P = 0.048) in the first week, and to 1.56% (P = 0.005) at 1
      month. Treatment failure was observed in three cases, requiring amniotic membrane
      transplantation in two patients and penetrating keratoplasty in one patient. At
      the end of the study, none of the patients displayed significant improvement in
      visual acuity. There were no systemic or local side effects of treatment.
      CONCLUSIONS: RGTA seems to be a potentially useful, alternative, noninvasive
      therapeutic approach in neurotrophic keratopathy management. However, randomized
      studies are necessary.

PMID- 23150627
TI  - Effects of gold nanoparticles on endotoxin-induced uveitis in rats.
AB  - PURPOSE: This study evaluates the effects of the gold nanoparticle in endotoxin
      induced uveitis in rats. METHODS: Adult male Wistar rats were divided into five
      groups: saline + saline, lipopolysaccharide (LPS) + saline, LPS + prednisolone,
      LPS + gold salt (GS) and LPS + gold nanoparticle (GNP). Two hours after LPS
      administration, prednisolone acetate 1%, GS, and GNP were topically applied to
      both eyes of rats and repeated every 6 hours for 24 hours. After 24 hours, rats
      were anesthetized and aqueous humor was sampled and the irides were removed.
      Aqueous humor TNF-alpha, myeloperoxidase activity were determined. Irides
      oxidative damage and content of toll-like receptor 4 (TLR4) and nuclear factor
      kappaB (NF-kappaB) were determined. RESULTS: The administration of LPS-induced
      eye inflammatory response characterized by an increase in aqueous humor TNF
      alpha, myeloperoxidase, and by irides oxidative damage. All these parameters were
      decreased by the administration of GNP. Since the inflammatory response secondary
      to LPS administration depends, in part, to the activation of the TLR4-NF-kappaB
      pathway we demonstrated here that a potential mechanism to explain the GNP
      effects was the decrease on TLR4 content and NF-kappaB activation. CONCLUSIONS:
      These findings suggest that topical GNP decreases intraocular inflammation and
      oxidative damage by interfering in the TLR4-NF-kappaB pathway.

PMID- 23150629
TI  - Accuracy and reproducibility of automated drusen segmentation in eyes with non
      neovascular age-related macular degeneration.
AB  - PURPOSE: To evaluate the accuracy and reproducibility of drusen quantification by
      an automated drusen segmentation algorithm in spectral domain optical coherence
      tomography (SD-OCT) images of eyes with non-neovascular age-related macular
      degeneration (AMD). METHODS: Drusen segmentation was performed using both a
      commercial automated algorithm (Cirrus OCT RPE analysis tool) and manual
      segmentation in 44 eyes of 30 subjects with dry AMD who underwent volume OCT
      scanning. The drusen (space between outer RPE layer and Bruch's membrane) was
      segmented automatically using an automated RPE tool and manually by 3D-OCTOR
      software. Drusen area and volume were calculated in all eyes. Age and visual
      acuity data were also collected. Reproducibility of manual and automated
      measurements was assessed by intraclass correlation (ICC). RESULTS: The mean age
      of subjects was 78.24 (+/- 9.4; range, 56-97 years). The mean logMAR (logarithm
      of the minimum angle of resolution) visual acuity was 0.4 (Snellen equivalent,
      ~20/50) (standard deviation, 0.40; range, 0-1.3). The mean (standard deviation)
      drusen area was 5.05 (3.67) mm(2) with manual segmentation and 4.66 (3.51) mm(2)
      with the automated RPE tool; the absolute difference was 2.63 (2.5) mm(2). The
      mean drusen volume was 1.49 (0.42) mm(3) with manual segmentation and 1.42 (0.43)
      mm(3) with the automated RPE tool; the absolute difference was 1.42 (0.43) mm(3).
      The agreement between manual and automated measurements of drusen volume (highest
      ICC = 0.95) was better than the agreement for drusen area (ICC = 0.65).
      CONCLUSIONS: The quantification of drusen area and volume using an automated RPE
      yielded better agreement for volume than for area when compared with human expert
      manual segmentation. Using this software, drusen volume measurements may be a
      useful tool for quantifying drusen burden in clinical trials and clinical
      practice.

PMID- 23150628
TI  - Immunoproteomic analysis of potential serum biomarker candidates in human
      glaucoma.
AB  - PURPOSE: Evidence supporting the immune system involvement in glaucoma includes
      increased titers of serum antibodies to retina and optic nerve proteins, although
      their pathogenic importance remains unclear. This study using an antibody-based
      proteomics approach aimed to identify disease-related antigens as candidate
      biomarkers of glaucoma. METHODS: Serum samples were collected from 111 patients
      with primary open-angle glaucoma and an age-matched control group of 49 healthy
      subjects without glaucoma. For high-throughput characterization of antigens,
      serum IgG was eluted from five randomly selected glaucomatous samples and
      analyzed by linear ion trap mass spectrometry (LC-MS/MS). Serum titers of
      selected biomarker candidates were then measured by specific ELISAs in the whole
      sample pool (including an additional control group of diabetic retinopathy).
      RESULTS: LC-MS/MS analysis of IgG elutes revealed a complex panel of proteins,
      including those detectable only in glaucomatous samples. Interestingly, many of
      these antigens corresponded to upregulated retinal proteins previously identified
      in glaucomatous donors (or that exhibited increased methionine oxidation).
      Moreover, additional analysis detected a greater immunoreactivity of the patient
      sera to glaucomatous retinal proteins (or to oxidatively stressed cell culture
      proteins), thereby suggesting the importance of disease-related protein
      modifications in autoantibody production/reactivity. As a narrowing-down strategy
      for selection of initial biomarker candidates, we determined the serum proteins
      overlapping with the retinal proteins known to be up-regulated in glaucoma. Four
      of the selected 10 candidates (AIF, cyclic AMP-responsive element binding
      protein, ephrin type-A receptor, and huntingtin) exhibited higher ELISA titers in
      the glaucomatous sera. CONCLUSIONS: A number of serum proteins identified by this
      immunoproteomic study of human glaucoma may represent diseased tissue-related
      antigens and serve as candidate biomarkers of glaucoma.

PMID- 23150630
TI  - Phosphatidic acid regulates microtubule organization by interacting with MAP65-1
      in response to salt stress in Arabidopsis.
AB  - Membrane lipids play fundamental structural and regulatory roles in cell
      metabolism and signaling. Here, we report that phosphatidic acid (PA), a product
      of phospholipase D (PLD), regulates MAP65-1, a microtubule-associated protein, in
      response to salt stress. Knockout of the PLDalpha1 gene resulted in greater NaCl
      induced disorganization of microtubules, which could not be recovered during or
      after removal of the stress. Salt affected the association of MAP65-1 with
      microtubules, leading to microtubule disorganization in pldalpha1cells, which was
      alleviated by exogenous PA. PA bound to MAP65-1, increasing its activity in
      enhancing microtubule polymerization and bundling. Overexpression of MAP65-1
      improved salt tolerance of Arabidopsis thaliana cells. Mutations of eight amino
      acids in MAP65-1 led to the loss of its binding to PA, microtubule-bundling
      activity, and promotion of salt tolerance. The pldalpha1 map65-1 double mutant
      showed greater sensitivity to salt stress than did either single mutant. These
      results suggest that PLDalpha1-derived PA binds to MAP65-1, thus mediating
      microtubule stabilization and salt tolerance. The identification of MAP65-1 as a
      target of PA reveals a functional connection between membrane lipids and the
      cytoskeleton in environmental stress signaling.

PMID- 23150631
TI  - Regulatory impact of RNA secondary structure across the Arabidopsis
      transcriptome.
AB  - The secondary structure of an RNA molecule plays an integral role in its
      maturation, regulation, and function. However, the global influence of this
      feature on plant gene expression is still largely unclear. Here, we use a high
      throughput, sequencing-based, structure-mapping approach in conjunction with
      transcriptome-wide sequencing of rRNA-depleted (RNA sequencing), small RNA, and
      ribosome-bound RNA populations to investigate the impact of RNA secondary
      structure on gene expression regulation in Arabidopsis thaliana. From this
      analysis, we find that highly unpaired and paired RNAs are strongly correlated
      with euchromatic and heterochromatic epigenetic histone modifications,
      respectively, providing evidence that secondary structure is necessary for these
      RNA-mediated posttranscriptional regulatory pathways. Additionally, we uncover
      key structural patterns across protein-coding transcripts that indicate RNA
      folding demarcates regions of protein translation and likely affects microRNA
      mediated regulation of mRNAs in this model plant. We further reveal that RNA
      folding is significantly anticorrelated with overall transcript abundance, which
      is often due to the increased propensity of highly structured mRNAs to be
      degraded and/or processed into small RNAs. Finally, we find that secondary
      structure affects mRNA translation, suggesting that this feature regulates plant
      gene expression at multiple levels. These findings provide a global assessment of
      RNA folding and its significant regulatory effects in a plant transcriptome.

PMID- 23150632
TI  - Identification and characterization of an epi-allele of FIE1 reveals a regulatory
      linkage between two epigenetic marks in rice.
AB  - DNA methylation and histone H3 Lys 9 dimethylation (H3K9me2) are important
      epigenetic repression marks for silencing transposons in heterochromatin and for
      regulating gene expression. However, the mechanistic relationship to other
      repressive marks, such as histone H3 Lys 27 trimethylation (H3K27me3) is unclear.
      FERTILIZATION-INDEPENDENT ENDOSPERM1 (FIE1) encodes an Esc-like core component of
      the Polycomb repressive complex 2, which is involved in H3K27me3-mediated gene
      repression. Here, we identify a gain-of-function epi-allele (Epi-df) of rice
      (Oryza sativa) FIE1; this allele causes a dwarf stature and various floral
      defects that are inherited in a dominant fashion. We found that Epi-df has no
      changes in nucleotide sequence but is hypomethylated in the 5' region of FIE1 and
      has reduced H3K9me2 and increased H3K4me3. In Epi-df, FIE1 was ectopically
      expressed and its imprinting was disrupted. FIE1 interacted with rice Enhancer of
      Zeste homologs, consistent with its role in H3K27me3 repression. Ectopic
      expression of FIE1 in Epi-df resulted in alteration of H3K27me3 levels in
      hundreds of genes. In summary, this work identifies an epi-allele involved in
      H3K27me3-mediated gene repression that itself is highly regulated by DNA
      methylation and histone H3K9me2, thereby shedding light on the link between DNA
      methylation and histone methylation, the two important epigenetic marks
      regulating rice development.

PMID- 23150633
TI  - FIMBRIN1 is involved in lily pollen tube growth by stabilizing the actin fringe.
AB  - An actin fringe structure in the subapex plays an important role in pollen tube
      tip growth. However, the precise mechanism by which the actin fringe is generated
      and maintained remains largely unknown. Here, we cloned a 2606-bp full-length
      cDNA encoding a deduced 77-kD fimbrin-like protein from lily (Lilium
      longiflorum), named FIMBRIN1 (FIM1). Ll-FIM1 was preferentially expressed in
      pollen and concentrated at actin fringe in the subapical region, as well as in
      longitudinal actin-filament bundles in the shank of pollen tubes. Microinjection
      of Ll-FIM1 antibody into lily pollen tubes inhibited tip growth and disrupted the
      actin fringe. Furthermore, we verified the function of Ll-FIM1 in the fim5 mutant
      of its closest relative, Arabidopsis thaliana. Pollen tubes of fim5 mutants grew
      with a larger diameter in early stages but could recover into normal forms in
      later stages, despite significantly slower growth rates. The actin fringe of the
      fim5 mutants, however, was impaired during both early and late stages.
      Impressively, stable expression of fim5pro:GFP:Ll-FIM1 rescued the actin fringe
      and the growth rate of Arabidopsis fim5 pollen tubes. In vitro biochemical
      analysis showed that Ll-FIM1 could bundle actin filaments. Thus, our study has
      identified a fimbrin that may stabilize the actin fringe by cross-linking actin
      filaments into bundles, which is important for proper tip growth of lily pollen
      tubes.

PMID- 23150634
TI  - Metabolic interactions between the Lands cycle and the Kennedy pathway of
      glycerolipid synthesis in Arabidopsis developing seeds.
AB  - It has been widely accepted that the primary function of the Lands cycle is to
      provide a route for acyl remodeling to modify fatty acid (FA) composition of
      phospholipids derived from the Kennedy pathway. Lysophosphatidylcholine
      acyltransferase (LPCAT) is an evolutionarily conserved key enzyme in the Lands
      cycle. In this study, we provide direct evidence that the Arabidopsis thaliana
      LPCATs, LPCAT1 and LPCAT2, participate in the Lands cycle in developing seeds. In
      spite of a substantially reduced initial rate of nascent FA incorporation into
      phosphatidylcholine (PC), the PC level in the double mutant lpcat1 lpcat2-2
      remained unchanged. LPCAT deficiency triggered a compensatory response of de novo
      PC synthesis and a concomitant acceleration of PC turnover that were attributable
      at least in part to PC deacylation. Acyl-CoA profile analysis revealed
      complicated metabolic alterations rather than merely reduced acyl group shuffling
      from PC in the mutant. Shifts in FA stereo-specific distribution in
      triacylglycerol of the mutant seed suggested a preferential retention of
      saturated acyl chains at the stereospecific numbering (sn)-1 position from PC and
      likely a channeling of lysophosphatidic acid, derived from PC, into the Kennedy
      pathway. Our study thus illustrates an intricate relationship between the Lands
      cycle and the Kennedy pathway.

PMID- 23150636
TI  - Author response: Axial length changes with shifts of gaze in myopes and
      emmetropes.

PMID- 23150637
TI  - Pupil dynamics and response amplitude: only size matters.

PMID- 23150635
TI  - Arabidopsis FHY3 and HY5 positively mediate induction of COP1 transcription in
      response to photomorphogenic UV-B light.
AB  - As sessile organisms, higher plants have evolved the capacity to sense and
      interpret diverse light signals to modulate their development. In Arabidopsis
      thaliana, low-intensity and long-wavelength UV-B light is perceived as an
      informational signal to mediate UV-B-induced photomorphogenesis. Here, we report
      that the multifunctional E3 ubiquitin ligase, CONSTITUTIVE PHOTOMORPHOGENESIS1
      (COP1), a known key player in UV-B photomorphogenic responses, is also a UV-B
      inducible gene. Two transcription factors, FAR-RED ELONGATED HYPOCOTYL3 (FHY3)
      and ELONGATED HYPOCOTYL5 (HY5), directly bind to distinct regulatory elements
      within the COP1 promoter, which are essential for the induction of the COP1 gene
      mediated by photomorphogenic UV-B signaling. Absence of FHY3 results in impaired
      UV-B-induced hypocotyl growth and reduced tolerance against damaging UV-B. Thus,
      FHY3 positively regulates UV-B-induced photomorphogenesis by directly activating
      COP1 transcription, while HY5 promotes COP1 expression via a positive feedback
      loop. Furthermore, FHY3 and HY5 physically interact with each other, and this
      interaction is diminished by UV-B. Together, our findings reveal that COP1 gene
      expression in response to photomorphogenic UV-B is controlled by a combinatorial
      regulation of FHY3 and HY5, and this UV-B-specific working mode of FHY3 and HY5
      is distinct from that in far-red light and circadian conditions.

PMID- 23150638
TI  - Is the diabetes educator better off now compared to last year?

PMID- 23150639
TI  - As one chapter ends, another begins.

PMID- 23150643
TI  - Intestinal volvulus in cetaceans.
AB  - Intestinal volvulus was recognized as the cause of death in 18 cetaceans,
      including 8 species of toothed whales (suborder Odontoceti). Cases originated
      from 11 institutions from around the world and included both captive (n = 9) and
      free-ranging (n = 9) animals. When the clinical history was available (n = 9),
      animals consistently demonstrated acute dullness 1 to 5 days prior to death. In 3
      of these animals (33%), there was a history of chronic gastrointestinal illness.
      The pathological findings were similar to those described in other animal species
      and humans, and consisted of intestinal volvulus and a well-demarcated segment of
      distended, congested, and edematous intestine with gas and bloody fluid contents.
      Associated lesions included congested and edematous mesentery and mesenteric
      lymph nodes, and often serofibrinous or hemorrhagic abdominal effusion. The
      volvulus involved the cranial part of the intestines in 85% (11 of 13). Potential
      predisposing causes were recognized in most cases (13 of 18, 72%) but were
      variable. Further studies investigating predisposing factors are necessary to
      help prevent occurrence and enhance early clinical diagnosis and management of
      the condition.

PMID- 23150644
TI  - NaStEP: a proteinase inhibitor essential to self-incompatibility and a positive
      regulator of HT-B stability in Nicotiana alata pollen tubes.
AB  - In Solanaceae, the self-incompatibility S-RNase and S-locus F-box interactions
      define self-pollen recognition and rejection in an S-specific manner. This
      interaction triggers a cascade of events involving other gene products unlinked
      to the S-locus that are crucial to the self-incompatibility response. To date,
      two essential pistil-modifier genes, 120K and High Top-Band (HT-B), have been
      identified in Nicotiana species. However, biochemistry and genetics indicate that
      additional modifier genes are required. We recently reported a Kunitz-type
      proteinase inhibitor, named NaStEP (for Nicotiana alata Stigma-Expressed
      Protein), that is highly expressed in the stigmas of self-incompatible Nicotiana
      species. Here, we report the proteinase inhibitor activity of NaStEP. NaStEP is
      taken up by both compatible and incompatible pollen tubes, but its suppression in
      Nicotiana spp. transgenic plants disrupts S-specific pollen rejection; therefore,
      NaStEP is a novel pistil-modifier gene. Furthermore, HT-B levels within the
      pollen tubes are reduced when NaStEP-suppressed pistils are pollinated with
      either compatible or incompatible pollen. In wild-type self-incompatible N.
      alata, in contrast, HT-B degradation occurs preferentially in compatible
      pollinations. Taken together, these data show that the presence of NaStEP is
      required for the stability of HT-B inside pollen tubes during the rejection
      response, but the underlying mechanism is currently unknown.

PMID- 23150645
TI  - Identification and characterization of the missing pyrimidine reductase in the
      plant riboflavin biosynthesis pathway.
AB  - Riboflavin (vitamin B2) is the precursor of the flavin coenzymes flavin
      mononucleotide and flavin adenine dinucleotide. In Escherichia coli and other
      bacteria, sequential deamination and reduction steps in riboflavin biosynthesis
      are catalyzed by RibD, a bifunctional protein with distinct pyrimidine deaminase
      and reductase domains. Plants have two diverged RibD homologs, PyrD and PyrR;
      PyrR proteins have an extra carboxyl-terminal domain (COG3236) of unknown
      function. Arabidopsis (Arabidopsis thaliana) PyrD (encoded by At4g20960) is known
      to be a monofunctional pyrimidine deaminase, but no pyrimidine reductase has been
      identified. Bioinformatic analyses indicated that plant PyrR proteins have a
      catalytically competent reductase domain but lack essential zinc-binding residues
      in the deaminase domain, and that the Arabidopsis PyrR gene (At3g47390) is
      coexpressed with riboflavin synthesis genes. These observations imply that PyrR
      is a pyrimidine reductase without deaminase activity. Consistent with this
      inference, Arabidopsis or maize (Zea mays) PyrR (At3g47390 or GRMZM2G090068)
      restored riboflavin prototrophy to an E. coli ribD deletant strain when
      coexpressed with the corresponding PyrD protein (At4g20960 or GRMZM2G320099) but
      not when expressed alone; the COG3236 domain was unnecessary for complementing
      activity. Furthermore, recombinant maize PyrR mediated NAD(P)H-dependent
      pyrimidine reduction in vitro. Import assays with pea (Pisum sativum)
      chloroplasts showed that PyrR and PyrD are taken up and proteolytically
      processed. Ablation of the maize PyrR gene caused early seed lethality. These
      data argue that PyrR is the missing plant pyrimidine reductase, that it is
      plastid localized, and that it is essential. The role of the COG3236 domain
      remains mysterious; no evidence was obtained for the possibility that it
      catalyzes the dephosphorylation that follows pyrimidine reduction.

PMID- 23150649
TI  - Lifestyle risk factors for ischemic stroke and transient ischemic attack in young
      adults in the Stroke in Young Fabry Patients study.
AB  - BACKGROUND AND PURPOSE: Although many stroke patients are young or middle-aged,
      risk factor profiles in these age groups are poorly understood. METHODS: The
      Stroke in Young Fabry Patients (sifap1) study prospectively recruited a large
      multinational European cohort of patients with cerebrovascular events aged 18 to
      55 years to establish their prevalence of Fabry disease. In a secondary analysis
      of patients with ischemic stroke or transient ischemic attack, we studied age-
      and sex-specific prevalences of various risk factors. RESULTS: Among 4467
      patients (median age, 47 years; interquartile range, 40-51), the most frequent
      well-documented and modifiable risk factors were smoking (55.5%), physical
      inactivity (48.2%), arterial hypertension (46.6%), dyslipidemia (34.9%), and
      obesity (22.3%). Modifiable less well-documented or potentially modifiable risk
      factors like high-risk alcohol consumption (33.0%) and short sleep duration
      (20.6%) were more frequent in men, and migraine (26.5%) was more frequent in
      women. Women were more often physically inactive, most pronouncedly at ages <35
      years (18-24: 38.2%; 25-34: 51.7%), and had high proportions of abdominal obesity
      at age 25 years or older (74%). Physical inactivity, arterial hypertension,
      dyslipidemia, obesity, and diabetes mellitus increased with age. CONCLUSIONS: In
      this large European cohort of young patients with acute ischemic cerebrovascular
      events, modifiable risk factors were highly prevalent, particularly in men and
      older patients. These data emphasize the need for vigorous primary and secondary
      prevention measures already in young populations targeting modifiable lifestyle
      vascular risk factors.

PMID- 23150650
TI  - Prestroke modified rankin stroke scale has moderate interobserver reliability and
      validity in an acute stroke setting.
AB  - BACKGROUND AND PURPOSE: The modified Rankin Scale (mRS) is the recommended
      functional outcome assessment in stroke trials. Utility of mRS may be limited by
      interobserver variability. prestroke function, described using mRS, is often used
      as trial entry criterion. We assessed the reliability and validity of prestroke
      mRS in acute stroke. METHODS: We present two complementary analyses of the
      properties of prestroke mRS: (1) Paired interviewers (trained in mRS) performed
      independently a blinded assessment of mRS and prestroke mRS. Interobserver
      variability was described using percentage agreement and weighted (kw) kappa
      statistics with 95% confidence interval (95% CI). Validity was assessed by
      comparing prestroke mRS with other markers of function (comorbidity; medication
      count; need for carers). (2) We further assessed validity using a larger
      retrospective dataset. We compared prestroke mRS with Charlson comorbidity index
      (CCI) and the Rockwood frailty index. Rank correlation coefficient or Fisher
      exact test were used as appropriate. RESULTS: Paired interviewers assessed 74
      stroke survivors. Median standard mRS was 4 (interquartile range [IQR], 2-4),
      median prestroke mRS was 1 (IQR, 0-3; range, 0-4). Reliability for standard mRS
      interview was 56% agreement, kw=0.55 (95% CI, 0.39-0.71). Reliability for
      prestroke mRS was 70%, kw=0.70 (95% CI, 0.53-0.87). The retrospective dataset
      described 231 subjects. In this data set, Spearman Rho for prestroke mRS and
      frailty index was J. 0.82 (95% CI, 0.78-0.86); CCI 0.50 (95% CI, 0.40-0.59);
      patient age 0.45 (95% CI, 0.34-0.54); medication count 0.28 (95% CI, 0.15-0.40).
      There was no association between need for carers and prestroke mRS (p=0.10).
      CONCLUSIONS: Interobserver reliability of prestroke mRS is limited but comparable
      with standard mRS. Poor correlation of prestroke mRS with certain markers of
      function suggests limited validity. Our data would suggest that relying on mRS
      alone may be a suboptimal measure of prestroke function and could potentially
      bias trial samples.

PMID- 23150651
TI  - Antithrombotic therapy and bleeding risk in a prospective cohort study of
      patients with cerebral cavernous malformations.
AB  - BACKGROUND AND PURPOSE: Cerebral cavernous malformations (CCMs) are one of the
      most frequently diagnosed vascular malformations of the brain and constitute a
      potential source of intracranial hemorrhage. In CCM patients suffering ischemic
      stroke or heart disease, the use of anticoagulants or antiplatelet therapy is
      generally avoided by fear of hemorrhagic complications, but no systematic studies
      exist to support this hypothesis. METHODS: We prospectively followed-up
      consecutive patients with a diagnosis of one or more CCMs in a prospective
      database since 2008. Retrospective data collection was used for patients with a
      diagnostic event or imaging studies done before first assessment. Symptomatic
      hemorrhage and other focal neurological events during prospective follow-up were
      defined according to the current guidelines of the Angioma Alliance Scientific
      Advisory board. RESULTS: A total of 87 patients were prospectively enrolled in
      our cohort [50 women (57%), mean age 44.8 years (SD+/-17.6), mean follow-up 3.9
      years], harboring a total of 738 CCMs. Fifty-five patients (63%) had a single
      CCM, and 32 patients (37%) had multiple CCMs. Longitudinal follow-up included 16
      (18%) patients receiving long-term antithrombotic therapy by antiplatelet
      treatment (n=11) or oral anticoagulants (n=5). During 5536 lesion-years of
      observation, none of the patients under antithrombotic therapy experienced CCM
      hemorrhage on follow-up. CONCLUSIONS: Our observational data suggest that long
      term antithrombotic treatment by antiplatelet drugs or warfarin does not increase
      the frequency of CCM-related hemorrhage. Patients harboring single or multiple
      CCMs suffering ischemic stroke or heart disease should not be withheld
      antithrombotic therapy.

PMID- 23150652
TI  - Impairment of cerebral autoregulation predicts delayed cerebral ischemia after
      subarachnoid hemorrhage: a prospective observational study.
AB  - BACKGROUND AND PURPOSE: Delayed cerebral ischemia (DCI) is a recognized
      contributor to unfavorable outcome after subarachnoid hemorrhage (SAH). Recent
      data challenge the concept of vasospasm as the sole cause of ischemia and suggest
      a multifactorial process with dysfunctional cerebral autoregulation as a
      component. We tested the hypothesis that early autoregulatory failure, detected
      using near-infrared spectroscopy-based index, TOxa and transcranial Doppler-based
      index, Sxa, can predict DCI. METHODS: In this prospective observational study we
      enrolled consecutive patients with aneurysmal SAH that occurred <5 days from
      admission. The primary end point was the occurrence of DCI within 21 days of
      ictus. The predictive value of autoregulatory disturbances detected in the first
      5 days was assessed using univarate proportional hazards model and a multivariate
      model. RESULTS: Ninety-eight patients were included. Univariate analysis
      demonstrated increased odds of developing DCI when early autoregulation failure
      was detected (odds ratio [OR], 7.46; 95% confidence interval [CI], 3.03-18.40 and
      OR, 4.52; 95% CI, 1.84-11.07 for Sxa and TOxa, respectively) but not TCD
      vasospasm (OR, 1.36; 95% CI, 0.56-3.33). In a multivariate model Sxa and TOxa
      remained independent predictors of DCI (OR, 12.66; 95% CI, 2.97-54.07 and OR,
      5.34; 95% CI, 1.25-22.84 for Sxa and TOxa, respectively). CONCLUSIONS: Disturbed
      autoregulation in the first 5 days after SAH significantly increases the risk of
      DCI. Autoregulatory disturbances can be detected using near-infrared spectroscopy
      and transcranial Doppler technologies.

PMID- 23150653
TI  - Soluble urokinase plasminogen activator receptor is associated with inflammation
      in the vulnerable human atherosclerotic plaque.
AB  - BACKGROUND AND PURPOSE: Recently, plasma soluble urokinase plasminogen activator
      receptor (suPAR) has gained interest as a marker of cardiovascular risk. suPAR is
      released through the cleavage of urokinase plasminogen activator receptor (uPAR),
      which is found in monocytes, activated T-lymphocytes and endothelial cells, all
      involved in atherosclerosis. suPAR levels have been well studied in plasma, but
      no studies have focused on suPAR in human atherosclerotic plaques. The aim of
      this study was to determine whether suPAR measured in the plaque is associated
      with symptomatic plaques and plaque inflammation. METHODS: Plasma and carotid
      plaques from 162 patients were analyzed. Lipids, collagen, uPAR, and macrophages
      were measured histologically. Cytokines and suPAR were measured in homogenized
      plaque extracts using multiplex immunoassay and ELISA, respectively. Plasma
      levels of suPAR were analysed with ELISA. CD3, CD4, as well as uPAR mRNA
      expression were assessed with quantitative real-time polymerase chain reaction in
      plaque homogenates from 123 patients. RESULTS: Plaque and plasma suPAR levels
      were higher in symptomatic patients compared with asymptomatic patients. Plaque
      suPAR levels correlated with plaque content of lipids and macrophages and with
      proinflammatory chemokines and cytokines monocyte chemoattractant protein 1,
      tumor necrosis factor alpha, interleukin 1beta, interleukin 6, platelet-derived
      growth factor AB/BB, monocyte inflammatory protein 1beta, regulated on activation
      normal T-cell expressed and secreted, and s-CD40L. uPAR mRNA and histological
      staining for uPAR correlated with plaque content of suPAR. CONCLUSIONS: This
      study shows that suPAR in human carotid plaques and plasma is associated with the
      presence of symptoms and that plaque suPAR is associated with the vulnerable
      inflammatory plaque. These findings strengthen the hypothesis of suPAR as a
      future marker of vulnerable atherosclerotic plaques.

PMID- 23150654
TI  - Nonvitamin-K-antagonist oral anticoagulants in patients with atrial fibrillation
      and previous stroke or transient ischemic attack: a systematic review and meta
      analysis of randomized controlled trials.
AB  - BACKGROUND AND PURPOSE: To assess whether the combined analysis of all phase III
      trials of nonvitamin-K-antagonist (non-VKA) oral anticoagulants in patients with
      atrial fibrillation and previous stroke or transient ischemic attack shows a
      significant difference in efficacy or safety compared with warfarin. METHODS: We
      searched PubMed until May 31, 2012, for randomized clinical trials using the
      following search items: atrial fibrillation, anticoagulation, warfarin, and
      previous stroke or transient ischemic attack. Studies had to be phase III trials
      in atrial fibrillation patients comparing warfarin with a non-VKA currently on
      the market or with the intention to be brought to the market in North America or
      Europe. Analysis was performed on intention-to-treat basis. A fixed-effects model
      was used as more appropriate than a random-effects model when combining a small
      number of studies. RESULTS: Among 47 potentially eligible articles, 3 were
      included in the meta-analysis. In 14 527 patients, non-VKAs were associated with
      a significant reduction of stroke/systemic embolism (odds ratios, 0.85 [95% CI,
      074-0.99]; relative risk reduction, 14%; absolute risk reduction, 0.7%; number
      needed to treat, 134 over 1.8-2.0 years) compared with warfarin. Non-VKAs were
      also associated with a significant reduction of major bleeding compared with
      warfarin (odds ratios, 0.86 [95% CI, 075-0.99]; relative risk reduction, 13%;
      absolute risk reduction, 0.8%; number needed to treat, 125), mainly driven by the
      significant reduction of hemorrhagic stroke (odds ratios, 0.44 [95% CI, 032
      0.62]; relative risk reduction, 57.9%; absolute risk reduction, 0.7%; number
      needed to treat, 139). CONCLUSIONS: In the context of the significant limitations
      of combining the results of disparate trials of different agents, non-VKAs seem
      to be associated with a significant reduction in rates of stroke or systemic
      embolism, hemorrhagic stroke, and major bleeding when compared with warfarin in
      patients with previous stroke or transient ischemic attack.

PMID- 23150655
TI  - Secondary signal change and an apparent diffusion coefficient decrease of the
      substantia nigra after striatal infarction.
AB  - BACKGROUND AND PURPOSE: Diffusion-weighted imaging can depict secondary signal
      change of the substantia nigra of patients with ipsilateral striatal infarction
      via a decrease in the apparent diffusion coefficient (ADC). Clinical predictors
      of this phenomenon remain unclear. METHODS: We assessed 98 stroke patients with
      acute ischemic lesions in the hemilateral basal ganglia, external capsule, or
      internal capsule. The ADC values of the bilateral substantia nigra obtained from
      a follow-up MRI, various clinical factors, and patients' outcome were analyzed.
      Nineteen patients who underwent a follow-up MRI within 3 days were excluded from
      analysis because none of them demonstrated a significant ADC change of substantia
      nigra. RESULTS: Of 79 patients, 21 (26.6%) revealed a decreased ADC in the
      substantia nigra. Ischemic lesions in the globus pallidus (odds ratio 12.90) and
      the presence of emboligenic diseases (odds ratio 6.95) were independent
      predictors for an ADC decrease in the substantia nigra. The clinical outcome 3
      months after stroke onset was not different between patients with an ADC decrease
      and patients without. CONCLUSIONS: A reduction of ADC in the substantia nigra
      after acute striatal infarction was more frequently observed when the globus
      pallidus was affected or when the patient had emboligenic diseases, however, did
      not necessarily relate to the patient's clinical outcome.

PMID- 23150656
TI  - Prevalence of poststroke cognitive impairment: South London Stroke Register 1995
      2010.
AB  - BACKGROUND AND PURPOSE: Stroke is a common long-term condition with an increasing
      incidence as the population ages. This study evaluates temporal changes in the
      prevalence of cognitive impairment after first-ever stroke stratified by
      sociodemography, vascular risk factors, and stroke subtypes, up to 15 years after
      stroke. METHODS: Data were collected between 1995 and 2010 (n=4212) from the
      community-based South London Stroke Register covering an inner-city multiethnic
      population of 271 817 inhabitants. Patients were assessed for cognitive function
      using Abbreviated Mental Test or Mini-Mental State Examination at the onset, 3
      months, and annually thereafter. All estimates were age adjusted to the European
      standard. RESULTS: The overall prevalence of cognitive impairment 3 months after
      stroke and at annual follow-up remained relatively unchanged at 22% (24% [95% CI,
      21.2-27.8] at 3 months; 22% [17.4-26.8] at 5 years to 21% [3.6-63.8] at 14
      years). In multivariate analyses, the poststroke prevalence ratio of cognitive
      impairment increased with older age (2% [1-3] for each year of age), ethnicity
      (2.2 [1.65-2.89]-fold higher among black group) and socioeconomic status (42% [8
      86] increased among manual workers). A significant, progressive trend of
      cognitive impairment was observed among patients with small vessel occlusion and
      lacunar infarction (average annual percentage change: 10% [7.9-12.8] and 2% [0.3
      2.7], respectively, up to 5 years after stroke). CONCLUSIONS: The prevalence of
      cognitive impairment after stroke remains persistently high over time, with
      variations being predominantly explained by sociodemographic characteristics.
      Given population growth and ageing demographics, effective preventive strategies
      and poststroke surveillance are needed to manage survivors with cognitive
      impairment.

PMID- 23150657
TI  - Analysis of a coordinated stroke center and regional stroke network on access to
      acute therapy and clinical outcomes.
AB  - BACKGROUND AND PURPOSE: Compare access and outcomes in a tertiary care community
      hospital (Saint Luke's Neuroscience Institute) and its stroke network to
      hospitals in 3 national databases. METHODS: Retrospective analysis of ischemic
      stroke patients (2005, 2007, 2010) in Saint Luke's (n=1576), Get With The
      Guidelines-Stroke (n=423 809), Premier (n=91 598), and Merci Registry (n=966).
      Study measures were use of computed tomography scans and tissue plasminogen
      activator (tPA), symptomatic intracranial hemorrhage, discharge disposition,
      discharge National Institutes of Health Stroke Scale scores, and 90-day modified
      Rankin Scores. RESULTS: Saint Luke's increased access to care with higher tPA use
      than other hospitals (17.2% received intravenous tPA therapy compared with 5.8%
      at Get With The Guidelines-Stroke hospitals, P<0.001; 22.1% of Saint Luke's
      patients received tPA by any route compared with 3.5% of Premier patients,
      P<0.001). Use of intravenous tPA within 4.5 hours of onset was associated with
      more discharges to home (odds ratio, 2.123; 95% confidence interval, 1.394-3.246)
      and improved National Institutes of Health Stroke Scale scores (P=0.001). Saint
      Luke's patients also were more likely than those in other hospitals to receive
      computed tomography scans (99.4% vs 58.6% at Premier hospitals). Embolectomy at
      Saint Luke's was associated with better outcomes than peer hospitals, and
      treatment at Saint Luke's was independently associated with more discharges to
      home (odds ratio, 3.92; 95% confidence interval, 1.84-8.32). In 2010, symptomatic
      intracranial hemorrhages after tPA therapy was similar for Saint Luke's patients
      and Premier patients (2.2% vs 1.5%; P=0.590). CONCLUSIONS: Regionally coordinated
      stroke programs can substantially improve access and patient outcomes.

PMID- 23150658
TI  - Treatment decisions after severe stroke: uncertainty and biases.

PMID- 23150659
TI  - Assembly of subtype 1 influenza neuraminidase is driven by both the transmembrane
      and head domains.
AB  - Neuraminidase (NA) is one of the two major influenza surface antigens and the
      main influenza drug target. Although NA has been well characterized and thought
      to function as a tetramer, the role of the transmembrane domain (TMD) in
      promoting proper NA assembly has not been systematically studied. Here, we
      demonstrate that in the absence of the TMD, NA is synthesized and transported in
      a predominantly inactive state. Substantial activity was rescued by progressive
      truncations of the stalk domain, suggesting the TMD contributes to NA maturation
      by tethering the stalk to the membrane. To analyze how the TMD supports NA
      assembly, the TMD was examined by itself. The NA TMD formed a homotetramer and
      efficiently trafficked to the plasma membrane, indicating the TMD and enzymatic
      head domain drive assembly together through matching oligomeric states. In
      support of this, an unrelated strong oligomeric TMD rescued almost full NA
      activity, whereas the weak oligomeric mutant of this TMD restored only half of
      wild type activity. These data illustrate that a large soluble domain can force
      assembly with a poorly compatible TMD; however, optimal assembly requires
      coordinated oligomerization between the TMD and the soluble domain.

PMID- 23150660
TI  - Activation of liver X receptor induces macrophage interleukin-5 expression.
AB  - IL-5 stimulates production of T15/EO6 IgM antibodies that can block the uptake of
      oxidized low density lipoprotein by macrophages, whereas a deficiency in
      macrophage IL-5 expression accelerates development of atherosclerosis. Liver X
      receptors (LXRs) are ligand-activated transcription factors that can induce
      macrophage ABCA1 expression and cholesterol efflux, thereby inhibiting the
      development of atherosclerosis. However, it remains unknown whether additional
      mechanisms, such as the regulation of macrophage IL-5 expression, are related to
      the anti-atherogenic properties of LXR. We initially defined IL-5 expression in
      macrophages where the LXR ligand (T0901317) induced macrophage IL-5 protein
      expression and secretion. The overexpression of LXR increased, whereas its
      knockdown inhibited IL-5 expression. Furthermore, we found that LXR activation
      increased IL-5 transcripts, promoter activity, formation of an LXR.LXR-responsive
      element complex, and IL-5 protein stability. In vivo, we found that T0901317
      increased IL-5 and total IgM levels in plasma and IL-5 expression in multiple
      tissues in wild type mice. In LDL receptor knock-out (LDLR(-/-)) mice, T0901317
      increased IL-5 expression in the aortic root area. Taken together, our studies
      demonstrate that macrophage IL-5 is a target gene for LXR activation, and the
      induction of macrophage IL-5 expression can be related to LXR-inhibited
      atherosclerosis.

PMID- 23150661
TI  - Cysteine cross-linking defines the extracellular gate for the Leishmania donovani
      nucleoside transporter 1.1 (LdNT1.1).
AB  - Equilibrative nucleoside transporters are a unique family of proteins that enable
      uptake of nucleosides/nucleobases into a wide range of eukaryotes and internalize
      a myriad of drugs used in the treatment of cancer, heart disease, AIDs, and
      parasitic infections. In previous work we generated a structural model for such a
      transporter, the LdNT1.1 nucleoside permease from the parasitic protozoan
      Leishmania donovani, using ab initio computation. The model suggested that
      aromatic residues present in transmembrane helices 1, 2, and 7 interact to form
      an extracellular gate that closes the permeation pathway in the inward-open
      conformation. Mutation of residues Phe-48(TM1) and Trp-75(TM2) abrogated
      transport activity, consistent with such prediction. In this study cysteine
      mutagenesis and oxidative cross-linking were combined to analyze proximity
      relationships of helices 1, 2, and 7 in LdNT1.1. Disulfide bond formation between
      introduced paired cysteines at the interface of such helices
      (A61C(TM1)/F74C(TM2), A61C(TM1)/G350C(TM7), and F74C(TM2)/G350C(TM7)) was
      analyzed by transport measurement and gel mobility shifts upon oxidation with Cu
      (II)-(1,10-phenanthroline)(3). In all cases cross-linking inhibited transport.
      However, if LdNT1.1 ligands were included during cross-linking, inhibition of
      transport was reduced, suggesting that ligands moved the three gating helices
      apart. Moreover, all paired cysteine mutants exhibited a mobility shift upon
      oxidation, corroborating the formation of a disulfide bond. These data support
      the notion that helices 1, 2, and 7 constitute the extracellular gate of LdNT1.1,
      thus further validating the computational model and the previously demonstrated
      importance of F48(TM1) and Trp-75(TM2) in tethering together helices that are
      part of the gate.

PMID- 23150662
TI  - Mycobacterium tuberculosis ESAT-6 exhibits a unique membrane-interacting activity
      that is not found in its ortholog from non-pathogenic Mycobacterium smegmatis.
AB  - Mycobacterium tuberculosis ESAT-6 (MtbESAT-6) reportedly shows membrane/cell
      lysis activity, and recently its biological roles in pathogenesis have been
      implicated in rupture of the phagosomes for bacterial cytosolic translocation.
      However, molecular mechanism of MtbESAT-6-mediated membrane interaction,
      particularly in relation with its biological functions in pathogenesis, is poorly
      understood. In this study, we investigated the pH-dependent membrane interaction
      of MtbESAT-6, MtbCFP-10, and the MtbESAT-6/CFP-10 heterodimer, by using liposomal
      model membranes that mimic phagosomal compartments. MtbESAT-6, but neither MtbCFP
      10 nor the heterodimer, interacted with the liposomal membranes at acidic
      conditions, which was evidenced by release of K(+) ions from the liposomes. Most
      importantly, the orthologous ESAT-6 from non-pathogenic Mycobacterium smegmatis
      (MsESAT-6) was essentially inactive in release of K(+). The differential membrane
      interactions between MtbESAT-6 and MsESAT-6 were further confirmed in an
      independent membrane leakage assay using the dye/quencher pair, 8-aminonapthalene
      1,3,6 trisulfonic acid (ANTS)/p-xylene-bis-pyridinium bromide (DPX). Finally,
      using intrinsic and extrinsic fluorescence approaches, we probed the pH-dependent
      conformational changes of MtbESAT-6 and MsESAT-6. At acidic pH conditions,
      MtbESAT-6 underwent a significant conformational change, which was featured by an
      increased solvent-exposed hydrophobicity, while MsESAT-6 showed little
      conformational change in response to acidification. In conclusion, we have
      demonstrated that MtbESAT-6 possesses a unique membrane-interacting activity that
      is not found in MsESAT-6 and established the utility of rigorous biochemical
      approaches in dissecting the virulence of M. tuberculosis.

PMID- 23150663
TI  - Dual function of mitochondrial Nm23-H4 protein in phosphotransfer and
      intermembrane lipid transfer: a cardiolipin-dependent switch.
AB  - The nucleoside diphosphate kinase Nm23-H4/NDPK-D forms symmetrical hexameric
      complexes in the mitochondrial intermembrane space with phosphotransfer activity
      using mitochondrial ATP to regenerate nucleoside triphosphates. We demonstrate
      the complex formation between Nm23-H4 and mitochondrial GTPase OPA1 in rat liver,
      suggesting its involvement in local and direct GTP delivery. Similar to OPA1,
      Nm23-H4 is further known to strongly bind in vitro to anionic phospholipids,
      mainly cardiolipin, and in vivo to the inner mitochondrial membrane. We show here
      that such protein-lipid complexes inhibit nucleoside diphosphate kinase activity
      but are necessary for another function of Nm23-H4, selective intermembrane lipid
      transfer. Mitochondrial lipid distribution was analyzed by liquid chromatography
      mass spectrometry using HeLa cells expressing either wild-type Nm23-H4 or a
      membrane binding-deficient mutant at a site predicted based on molecular modeling
      to be crucial for cardiolipin binding and transfer mechanism. We found that wild
      type, but not the mutant enzyme, selectively increased the content of cardiolipin
      in the outer mitochondrial membrane, but the distribution of other more abundant
      phospholipids (e.g. phosphatidylcholine) remained unchanged. HeLa cells
      expressing the wild-type enzyme showed increased accumulation of Bax in
      mitochondria and were sensitized to rotenone-induced apoptosis as revealed by
      stimulated release of cytochrome c into the cytosol, elevated caspase 3/7
      activity, and increased annexin V binding. Based on these data and molecular
      modeling, we propose that Nm23-H4 acts as a lipid-dependent mitochondrial switch
      with dual function in phosphotransfer serving local GTP supply and cardiolipin
      transfer for apoptotic signaling and putative other functions.

PMID- 23150664
TI  - Altering hydrophobic sequence lengths shows that hydrophobic mismatch controls
      affinity for ordered lipid domains (rafts) in the multitransmembrane strand
      protein perfringolysin O.
AB  - The hypothesis that mismatch between transmembrane (TM) length and bilayer width
      controls TM protein affinity for ordered lipid domains (rafts) was tested using
      perfringolysin O (PFO), a pore-forming cholesterol-dependent cytolysin. PFO forms
      a multimeric barrel with many TM segments. The properties of PFO mutants with
      lengthened or shortened TM segments were compared with that of PFO with wild type
      TM sequences. Both mutant and wild type length PFO exhibited cholesterol
      dependent membrane insertion. Maximal PFO-induced pore formation occurred in
      vesicles with wider bilayers for lengthened TM segments and in thinner bilayers
      for shortened TM segments. In diC(18:0) phosphatidylcholine (PC)/diC(14:1)
      PC/cholesterol vesicles, which form ordered domains with a relatively thick
      bilayer and disordered domains with a relatively thin bilayer, affinity for
      ordered domains was greatest with lengthened TM segments and least with shortened
      TM segments as judged by FRET. Similar results were observed by microscopy in
      giant vesicles containing sphingomyelin in place of diC(18:0) PC. In contrast, in
      diC(16:0) PC/diC(14:0) PC/diC(20:1) PC/cholesterol vesicles, which should form
      ordered domains with a relatively thin bilayer and disordered domains with a
      relatively thick bilayer, relative affinity for ordered domains was greatest with
      shortened TM segments and least with lengthened TM segments. The inability of
      multi-TM segment proteins (unlike single TM segment proteins) to adapt to
      mismatch by tilting may explain the sensitivity of raft affinity to mismatch. The
      difference in width sensitivity for single and multi-TM helix proteins may link
      raft affinity to multimeric state and thus control the assembly of multimeric TM
      complexes in rafts.

PMID- 23150666
TI  - The polybasic insertion in autotaxin alpha confers specific binding to heparin
      and cell surface heparan sulfate proteoglycans.
AB  - Autotaxin (ATX) is a secreted lysophospholipase D that generates the lipid
      mediator lysophosphatidic acid (LPA), playing a key role in diverse physiological
      and pathological processes. ATX exists in distinct splice variants, but isoform
      specific functions remain elusive. Here we characterize the ATXalpha isoform,
      which differs from the canonical form (ATXbeta) in having a 52-residue polybasic
      insertion of unknown function in the catalytic domain. We find that the ATXalpha
      insertion is susceptible to cleavage by extracellular furin-like endoproteases,
      but cleaved ATXalpha remains structurally and functionally intact due to strong
      interactions within the catalytic domain. Through ELISA and surface plasmon
      resonance assays, we show that ATXalpha binds specifically to heparin with high
      affinity (K(d) ~10(-8) M), whereas ATXbeta does not; furthermore, heparin
      moderately enhanced the lysophospholipase D activity of ATXalpha. We further show
      that ATXalpha, but not ATXbeta, binds abundantly to SKOV3 carcinoma cells.
      ATXalpha binding was abolished after treating the cells with heparinase III, but
      not after chondroitinase treatment. Thus, the ATXalpha insertion constitutes a
      cleavable heparin-binding domain that mediates interaction with heparan sulfate
      proteoglycans, thereby targeting LPA production to the plasma membrane.

PMID- 23150667
TI  - Identification of the components of a glycolytic enzyme metabolon on the human
      red blood cell membrane.
AB  - Glycolytic enzymes (GEs) have been shown to exist in multienzyme complexes on the
      inner surface of the human erythrocyte membrane. Because no protein other than
      band 3 has been found to interact with GEs, and because several GEs do not bind
      band 3, we decided to identify the additional membrane proteins that serve as
      docking sites for GE on the membrane. For this purpose, a method known as "label
      transfer" that employs a photoactivatable trifunctional cross-linking reagent to
      deliver a biotin from a derivatized GE to its binding partner on the membrane was
      used. Mass spectrometry analysis of membrane proteins that were biotinylated
      following rebinding and photoactivation of labeled GAPDH, aldolase, lactate
      dehydrogenase, and pyruvate kinase revealed not only the anticipated binding
      partner, band 3, but also the association of GEs with specific peptides in alpha-
      and beta-spectrin, ankyrin, actin, p55, and protein 4.2. More importantly, the
      labeled GEs were also found to transfer biotin to other GEs in the complex,
      demonstrating for the first time that GEs also associate with each other in their
      membrane complexes. Surprisingly, a new GE binding site was repeatedly identified
      near the junction of the membrane-spanning and cytoplasmic domains of band 3, and
      this binding site was confirmed by direct binding studies. These results not only
      identify new components of the membrane-associated GE complexes but also provide
      molecular details on the specific peptides that form the interfacial contacts
      within each interaction.

PMID- 23150668
TI  - Polycomb group protein PHF1 regulates p53-dependent cell growth arrest and
      apoptosis.
AB  - Polycomb group protein PHF1 is well known as a component of a novel EED
      EZH2.Polycomb repressive complex 2 complex and plays important roles in H3K27
      methylation and Hox gene silencing. PHF1 is also involved in the response to DNA
      double-strand breaks in human cells, promotes nonhomologous end-joining processes
      through interaction with Ku70/Ku80. Here, we identified another function of PHF1
      as a potential p53 pathway activator in a pathway screen using luminescence
      reporter assay. Subsequent studies showed PHF1 directly interacts with p53
      proteins both in vivo and in vitro and co-localized in nucleus. PHF1 binds to the
      C-terminal regulatory domain of p53. Overexpression of PHF1 elevated p53 protein
      level and prolonged its turnover. Knockdown of PHF1 reduced p53 protein level and
      its target gene expression both in normal state and DNA damage response.
      Mechanically, PHF1 protects p53 proteins from MDM2-mediated ubiquitination and
      degradation. Furthermore, we showed that PHF1 regulates cell growth arrest and
      etoposide-induced apoptosis in a p53-dependent manner. Finally, PHF1 expression
      was significantly down-regulated in human breast cancer samples. Taken together,
      we establish PHF1 as a novel positive regulator of the p53 pathway. These data
      shed light on the potential roles of PHF1 in tumorigenesis and/or tumor
      progression.

PMID- 23150669
TI  - The mammalian proteins MMS19, MIP18, and ANT2 are involved in cytoplasmic iron
      sulfur cluster protein assembly.
AB  - Iron-sulfur (Fe-S) clusters are essential cofactors of proteins with a wide range
      of biological functions. A dedicated cytosolic Fe-S cluster assembly (CIA) system
      is required to assemble Fe-S clusters into cytosolic and nuclear proteins. Here,
      we show that the mammalian nucleotide excision repair protein homolog MMS19 can
      simultaneously bind probable cytosolic iron-sulfur protein assembly protein CIAO1
      and Fe-S proteins, confirming that MMS19 is a central protein of the CIA
      machinery that brings Fe-S cluster donor proteins and the receiving apoproteins
      into proximity. In addition, we show that mitotic spindle-associated MMXD complex
      subunit MIP18 also interacts with both CIAO1 and Fe-S proteins. Specifically, it
      binds the Fe-S cluster coordinating regions in Fe-S proteins. Furthermore, we
      show that ADP/ATP translocase 2 (ANT2) interacts with Fe-S apoproteins and MMS19
      in the CIA complex but not with the individual proteins. Together, these results
      elucidate the composition and interactions within the late CIA complex.

PMID- 23150670
TI  - Peptide derived from HIV-1 TAT protein destabilizes a monolayer of endothelial
      cells in an in vitro model of the blood-brain barrier and allows permeation of
      high molecular weight proteins.
AB  - Most chemotherapeutic agents are blood-brain barrier (BBB) impermeants. HIV-1
      derived TAT protein variants contain a transmembrane domain, which may enable
      them to cross the BBB and reach the brain. Here we synthesized CAYGRKKRRQRRR, a
      peptide containing a cysteine moiety attached to the N terminus of the
      transmembrane domain (C-TAT peptide), and studied its effects in an in vitro BBB
      model, which we found to reflect penetration by a receptor-independent pathway.
      Incubation of the brain capillary endothelial cell monolayer with 0.3-0.6
      MUmol/ml of this C-TAT peptide, for a period of 1-2 h, destabilizes brain
      capillary endothelial cell monolayer and introduces the ability of impermeant
      therapeutic agents including high molecular weight proteins to penetrate it
      substantially. The cysteinyl moiety at position 1 of the C-TAT peptide
      contributes largely to the destabilizing potency and the penetration efficacy of
      impermeant substances. The destabilizing effect was reversed using heparin. In
      summary, experimental conditions allowing a significant increase in entry of
      impermeant low and high molecular weight substances from the luminal (blood) to
      the abluminal side (brain) were found in an in vitro BBB model reflecting in vivo
      protein penetrability by a receptor-independent pathway.

PMID- 23150671
TI  - Characterization of the Staphylococcus aureus rRNA methyltransferase encoded by
      orfX, the gene containing the staphylococcal chromosome Cassette mec (SCCmec)
      insertion site.
AB  - The gene orfX is conserved among all staphylococci, and its complete sequence is
      maintained upon insertion of the staphylococcal chromosome cassette mec (SCCmec)
      genomic island, containing the gene encoding resistance to beta-lactam
      antibiotics (mecA), into its C terminus. The function of OrfX has not been
      determined. We show that OrfX was constitutively produced during growth, that
      orfX could be inactivated without altering bacterial growth, and that insertion
      of SCCmec did not alter gene expression. We solved the crystal structure of OrfX
      at 1.7 A and found that it belongs to the S-adenosyl-L-methionine (AdoMet)
      dependent alpha/beta-knot superfamily of SPOUT methyltransferases (MTases), with
      a high structural homology to YbeA, the gene product of the Escherichia coli 70 S
      ribosomal MTase RlmH. MTase activity was confirmed by demonstrating the OrfX
      dependent methylation of the Staphylococcus aureus 70 S ribosome. When OrfX was
      crystallized in the presence of its AdoMet substrate, we found that each monomer
      of the homodimeric structure bound AdoMet in its active site. Solution studies
      using isothermal titration calorimetry confirmed that each monomer bound AdoMet
      but with different binding affinities (K(d) = 52 +/- 0.4 and 606 +/- 2 MUm). In
      addition, the structure shows that the AdoMet-binding pocket, formed by a deep
      trefoil knot, contains a bound phosphate molecule, which is the likely nucleotide
      methylation site. This study represents the first characterization of a
      staphylococcal ribosomal MTase and provides the first crystal structure of a
      member of the alpha/beta-knot superfamily of SPOUT MTases in the RlmH or COG1576
      family with bound AdoMet.

PMID- 23150672
TI  - The first structure of polarity suppression protein, Psu from enterobacteria
      phage P4, reveals a novel fold and a knotted dimer.
AB  - Psu is a capsid decoration protein of bacteriophage P4 and acts as an
      antiterminator of Rho-dependent transcription termination in bacteria. So far, no
      structures have been reported for the Psu protein or its homologues. Here, we
      report the first structure of Psu solved by the Hg(2+) single wavelength
      anomalous dispersion method, which reveals that Psu exists as a knotted homodimer
      and is first of its kind in nature. Each monomer of Psu attains a novel fold
      around a tight coiled-coil motif. CD spectroscopy and the structure of an
      engineered disulfide-bridged Psu derivative reveal that the protein folds
      reversibly and reassembles by itself into the knotted dimeric conformation
      without the requirement of any chaperone. This structure would help to explain
      the functional properties of the protein and can be used as a template to design
      a minimal peptide fragment that can be used as a drug against Rho-dependent
      transcription termination in bacteria.

PMID- 23150673
TI  - C1q-induced LRP1B and GPR6 proteins expressed early in Alzheimer disease mouse
      models, are essential for the C1q-mediated protection against amyloid-beta
      neurotoxicity.
AB  - Complement protein C1q is induced in the brain in response to a variety of
      neuronal injuries, including Alzheimer disease (AD), and blocks fibrillar amyloid
      beta (fAbeta) neurotoxicity in vitro. Here, we show that C1q protects immature
      and mature primary neurons against fAbeta toxicity, and we report for the first
      time that C1q prevents toxicity induced by oligomeric forms of amyloid-beta
      (Abeta). Gene expression analysis reveals C1q-activated phosphorylated cAMP
      response element-binding protein and AP-1, two transcription factors associated
      with neuronal survival and neurite outgrowth, and increased LRP1B and G protein
      coupled receptor 6(GPR6) expression in fAbeta-injured neurons. Silencing of cAMP
      response element-binding protein, LRP1B or GPR6 expression inhibited C1q-mediated
      neuroprotection from fAbeta-induced injury. In addition, C1q altered the
      association of oligomeric Abeta and fAbeta with neurons. In vivo, increased
      hippocampal expression of C1q, LRP1B, and GPR6 is observed as early as 2 months
      of age in the 3 * Tg mouse model of AD, whereas no such induction of LRP1B and
      GPR6 was seen in C1q-deficient AD mice. In contrast, expression of C1r and C1s,
      proteases required to activate the classical complement pathway, and C3 showed a
      significant age-dependent increase only after 10-13 months of age when Abeta
      plaques start to accumulate in this AD model. Thus, our results identify pathways
      by which C1q, up-regulated in vivo early in response to injury without the
      coordinate induction of other complement components, can induce a program of gene
      expression that promotes neuroprotection and thus may provide protection against
      Abeta in preclinical stages of AD and other neurodegenerative processes.

PMID- 23150674
TI  - An advanced glycation end product (AGE)-receptor for AGEs (RAGE) axis restores
      adipogenic potential of senescent preadipocytes through modulation of p53 protein
      function.
AB  - The impaired adipogenic potential of senescent preadipocytes is a hallmark of
      adipose aging and aging-related adipose dysfunction. Although advanced glycation
      end products (AGEs) derived from both foods and endogenous nonenzymatic glycation
      and AGE-associated signaling pathways are known to play a key role in aging and
      its related diseases, the role of AGEs in adipose aging remains elusive. We show
      a novel pro-adipogenic function of AGEs in replicative senescent preadipocytes
      and mouse embryonic fibroblasts, as well as primary preadipocytes isolated from
      aged mice. Using glycated bovine serum albumin (BSA) as a model protein of AGEs,
      we found that glycated BSA restores the impaired adipogenic potential of
      senescent preadipocytes in vitro and ex vivo. However, glycated BSA showed no
      effect on adipogenesis in nonsenescent preadipocytes. The AGE-induced receptor
      for AGE (RAGE) expression is required for the pro-adipogenic function of AGEs in
      senescent preadipocytes. RAGE is required for impairment of p53 expression and
      p53 function in regulating p21 expression in senescent preadipocytes. We also
      observed a direct binding between RAGE and p53 in senescent preadipocytes. Taken
      together, our findings reveal a novel pro-adipogenic function of the AGE-RAGE
      axis in p53-regulated adipogenesis of senescent preadipocytes, providing new
      insights into aging-dependent adiposity by diet-driven and/or endogenous glycated
      proteins.

PMID- 23150675
TI  - Myotubularin-related protein 4 (MTMR4) attenuates BMP/Dpp signaling by
      dephosphorylation of Smad proteins.
AB  - Bone morphogenetic proteins (BMPs) signaling essentially regulates a wide range
      of biological responses. Although multiple regulators at different layers of the
      receptor-effectors axis have been identified, the mechanisms of homeostatic BMP
      signaling remain vague. Herein we demonstrated that myotubularin-related protein
      4 (MTMR4), a FYVE domain-containing dual-specificity protein phosphatase (DUSP),
      preferentially associated with and dephosphorylated the activated R-Smads in
      cytoplasm, which is a critical checkpoint in BMP signal transduction. Therefore,
      transcriptional activation by BMPs was tightly controlled by the expression level
      and the intrinsic phosphatase activity of MTMR4. More profoundly, ectopic
      expression of MTMR4 or its Drosophila homolog CG3632 genetically interacted with
      BMP/Dpp signaling axis in regulation of the vein development of Drosophila wings.
      By doing so, MTMR4 could interact with and dephosphorylate Mothers against
      Decapentaplegic (Mad), the sole R-Smad in Drosophila BMP pathway, and hence
      affected the target genes expression of Mad. In conclusion, this study has
      suggested that MTMR4 is a necessary negative modulator for the homeostasis of
      BMP/Dpp signaling.

PMID- 23150677
TI  - Further insights into the pathogenesis of primary hyperparathyroidism: a nested
      case-control study.
AB  - CONTEXT: The pathogenesis of primary hyperparathyroidism (PHPT) is largely
      unknown. OBJECTIVE: The objective of the study was to ascertain the plasma levels
      of calcium, PTH, and 25-hydroxyvitamin D (25OHD) as measured prior to a clinical
      diagnosis of PHPT. STUDY SUBJECTS: Within three population-based cohorts, we
      identified participants diagnosed with PHPT after their inclusion. Cases (n =
      117) were compared with age, gender, and season-matched controls (n = 233).
      RESULTS: Time from inclusion until a diagnosis of PHPT was median 5.6 yr.
      Parathyroidectomy was performed in 97%. At the cohort inclusion, undiagnosed PHPT
      was present in 63% of the cases. Among those without PHPT at inclusion (n = 43),
      55% had normocalcemic hyperparathyroidism (vs. 21% in the matched controls, P <
      0.01), and 31% had normoparathyroid hypercalcemia. Overall, 25OHD levels were
      lower in the cases. Compared with their matched controls, 25OHD levels were lower
      in normocalcemic hyperparathyroidism but not in normoparathyroid hypercalcemia.
      An adenoma was removed from 78% of the cases with normocalcemic
      hyperparathyroidism, whereas 39% of the cases with normoparathyroid hypercalcemia
      had parathyroid hyperplasia (P = 0.02). Overlap performance showed a positive
      predictive value for later PHPT of 95% for plasma calcium levels greater than
      2.52 mmol/liter. Excluding cases with vitamin D insufficiency, the positive
      predictive value for later PHPT was 83% for PTH levels greater than 5.0
      pmol/liter. CONCLUSION: Years prior to a clinical diagnosis of PHPT, calcium
      homeostasis shows signs of perturbations. Latent PHPT may be characterized by
      either normocalcemic hyperparathyroidism or normoparathyroid hypercalcemia. Such
      patients should be offered long-term follow-up to ascertain whether their
      biochemical profile represents an early state of PHPT.

PMID- 23150676
TI  - Activation of placental mTOR signaling and amino acid transporters in obese women
      giving birth to large babies.
AB  - CONTEXT: Babies of obese women are often large at birth, which is associated with
      perinatal complications and metabolic syndrome later in life. The mechanisms
      linking maternal obesity to fetal overgrowth are largely unknown. OBJECTIVE: We
      tested the hypothesis that placental insulin/IGF-I and mammalian target of
      rapamycin (mTOR) signaling is activated and amino acid transporter activity is
      increased in large babies of obese women. DESIGN AND SETTING: Pregnant women were
      recruited prospectively for collection of placental tissue at a university
      hospital and academic biomedical center. PATIENTS OR OTHER PARTICIPANTS: Twenty
      three Swedish pregnant women with first trimester body mass index ranging from
      18.5 to 44.9 kg/m(2) and with uncomplicated pregnancies participated in the
      study. INTERVENTIONS: There were no interventions. MAIN OUTCOME MEASURES: We
      determined the phosphorylation of key signaling molecules (including Akt, IRS-1,
      S6K1, 4EBP-1, RPS6, and AMPK) in the placental insulin/IGF-I, AMPK, and mTOR
      signaling pathways. The activity and protein expression of the amino acid
      transporter systems A and L were measured in syncytiotrophoblast microvillous
      plasma membranes. RESULTS: Birth weights (range, 3025-4235 g) were positively
      correlated to maternal body mass index (P < 0.05). The activity of placental
      insulin/IGF-I and mTOR signaling was positively correlated (P < 0.001), whereas
      AMPK phosphorylation was inversely (P < 0.05) correlated to birth weight.
      Microvillous plasma membrane system A, but not system L, activity and protein
      expression of the system A isoform SNAT2 were positively correlated to birth
      weight (P < 0.001). CONCLUSIONS: Up-regulation of specific placental amino acid
      transporter isoforms may contribute to fetal overgrowth in maternal obesity. This
      effect may be mediated by activation of insulin/IGF-I and mTOR signaling
      pathways, which are positive regulators of placental amino acid transporters.

PMID- 23150678
TI  - The importance of palmitoleic acid to adipocyte insulin resistance and whole-body
      insulin sensitivity in type 1 diabetes.
AB  - CONTEXT: Type 1 diabetes is an insulin-resistant state, but it is less clear
      which tissues are affected. Our previous report implicated skeletal muscle and
      liver insulin resistance in people with type 1 diabetes, but this occurred
      independently of generalized, visceral, or ectopic fat. OBJECTIVE: The aim of the
      study was to measure adipose tissue insulin sensitivity and plasma triglyceride
      composition in individuals with type 1 diabetes after overnight insulin infusion
      to lower fasting glucose. DESIGN, PATIENTS, AND METHODS: Fifty subjects (25
      individuals with type 1 diabetes and 25 controls without) were studied. After 3 d
      of dietary control and overnight insulin infusion, we performed a three-stage
      hyperinsulinemic/euglycemic clamp infusing insulin at 4, 8, and 40 mU/m(2) . min.
      Infusions of [1,1,2,3,3-(2)H(2)]glycerol and [1-(13)C]palmitate were used to
      quantify lipid metabolism. RESULTS: Basal glycerol and palmitate rates of
      appearance were similar between groups, decreased more in control subjects during
      the first two stages of the clamp, and similarly suppressed during the highest
      insulin dose. The concentration of insulin required for 50% inhibition of
      lipolysis was twice as high in individuals with type 1 diabetes. Plasma
      triglyceride saturation was similar between groups, but palmitoleic acid in
      plasma triglyceride was inversely related to adipocyte insulin sensitivity.
      Unesterified palmitoleic acid in plasma was positively related to insulin
      sensitivity in controls, but not in individuals with type 1 diabetes.
      CONCLUSIONS: Adipose tissue insulin resistance is a significant feature of type 1
      diabetes. Palmitoleic acid is not related to insulin sensitivity in type 1
      diabetes, as it was in controls, suggesting a novel mechanism for insulin
      resistance in this population.

PMID- 23150680
TI  - Normal insulin-like peptide-3 levels despite low testosterone in adult males with
      Prader-Willi syndrome: variations in Leydig cell function from infancy through
      adulthood.
AB  - BACKGROUND: Cryptorchidism, incomplete pubertal development, and low testosterone
      are manifestations of hypogonadism in Prader-Willi syndrome (PWS). Insulin-like
      peptide-3 (INSL3) facilitates testicular descent in the fetus and reflects Leydig
      cell number in adults. INSL3 levels in PWS have not been previously reported.
      OBJECTIVES: The objectives of the study were to characterize the age-related
      changes in INSL3 in PWS males and correlate INSL3 with unilateral vs. bilateral
      cryptorchidism, body mass index, gonadotropins, testosterone, anti-mullerian
      hormone (AMH), and inhibin B. STUDY DESIGN AND PARTICIPANTS: We measured INSL3,
      LH, FSH, testosterone, AMH, and inhibin B in 40 PWS males (23 deletion, 17
      uniparental disomy) aged 2 months to 36 yr. Control samples for INSL3 were
      obtained from 365 normal males, aged 1 d to 36 yr. RESULTS: INSL3 levels (mean
      and range) for PWS age groups younger than 6 months, 0.5-10.0 yr, 10.1-19.0 yr,
      and older than 19.0 yr were 217 (68-380), 42 (16-112), 390 (16-1028), and 642
      (290-964) pg/ml, respectively, and did not differ significantly from values for
      normal males. In seven of 14 boys aged 10.1-19 yr, INSL3, testosterone, and LH
      were low (37.4 +/- 19.4 pg/ml, 1.44 +/- 0.46 nmol/liter, 0.3 +/- 0.6 IU/liter).
      The other seven with higher INSL3, testosterone, and LH (693.1 +/- 305.8 pg/ml,
      5.91 +/- 2.77 nmol/liter, 2.7 +/-1.9 IU/liter) had more advanced pubertal
      development. INSL3 was normal in seven of nine males aged older than 19 yr,
      despite low testosterone in six. After controlling for age, INSL3 correlated with
      LH (P = 0.005) and testosterone (P < 0.001) but not with FSH, AMH, or inhibin B.
      CONCLUSIONS: Most PWS males have normal INSL3 levels. By contrast, testosterone
      levels after infancy are low. These findings suggest a specific defect in Leydig
      cell function.

PMID- 23150679
TI  - MicroRNA expression array identifies novel diagnostic markers for conventional
      and oncocytic follicular thyroid carcinomas.
AB  - OBJECTIVE: The most difficult thyroid tumors to be diagnosed by cytology and
      histology are conventional follicular carcinomas (cFTCs) and oncocytic follicular
      carcinomas (oFTCs). Several microRNAs (miRNAs) have been previously found to be
      consistently deregulated in papillary thyroid carcinomas; however, very limited
      information is available for cFTC and oFTC. The aim of this study was to explore
      miRNA deregulation and find candidate miRNA markers for follicular carcinomas
      that can be used diagnostically. DESIGN: Thirty-eight follicular thyroid
      carcinomas (21 cFTCs, 17 oFTCs) and 10 normal thyroid tissue samples were studied
      for expression of 381 miRNAs using human microarray assays. Expression of
      deregulated miRNAs was confirmed by individual RT-PCR assays in all samples. In
      addition, 11 follicular adenomas, two hyperplastic nodules (HNs), and 19 fine
      needle aspiration samples were studied for expression of novel miRNA markers
      detected in this study. RESULTS: The unsupervised hierarchical clustering
      analysis demonstrated individual clusters for cFTC and oFTC, indicating the
      difference in miRNA expression between these tumor types. Both cFTCs and oFTCs
      showed an up-regulation of miR-182/-183/-221/-222/-125a-3p and a down-regulation
      of miR-542-5p/-574-3p/-455/-199a. Novel miRNA (miR-885-5p) was found to be
      strongly up-regulated (>40-fold) in oFTCs but not in cFTCs, follicular adenomas,
      and HNs. The classification and regression tree algorithm applied to fine-needle
      aspiration samples demonstrated that three dysregulated miRNAs (miR-885-5p/-221/
      574-3p) allowed distinguishing follicular thyroid carcinomas from benign HNs with
      high accuracy. CONCLUSIONS: In this study we demonstrate that different
      histopathological types of follicular thyroid carcinomas have distinct miRNA
      expression profiles. MiR-885-5p is highly up-regulated in oncocytic follicular
      carcinomas and may serve as a diagnostic marker for these tumors. A small set of
      deregulated miRNAs allows for an accurate discrimination between follicular
      carcinomas and hyperplastic nodules and can be used diagnostically in fine-needle
      aspiration biopsies.

PMID- 23150681
TI  - Sympathetic paraganglioma in a patient with unrepaired tetralogy of Fallot: a
      case report and review of the literature.
AB  - CONTEXT: Paragangliomas are a type of neuroendocrine tumor that has been reported
      to be present in patients with cyanotic congenital heart disease. This report
      documents the first case of a patient with successful resection of a sympathetic
      paraganglioma in the setting of unrepaired tetralogy of Fallot, the most common
      cause of cyanotic heart disease, with pulmonary atresia. OBJECTIVE: We present a
      33-yr-old woman with hypertensive crises from a paraganglioma who presented for
      surgical resection. PATIENT AND METHODS: The patient's preoperative workup was
      consistent with a functioning sympathetic paraganglioma. Preoperative
      transesophageal echocardiogram displayed normal ventricular function, moderate
      severe right ventricular hypertrophy, severe right ventricular hypertension, an
      overriding aorta, bidirectional shunting, pulmonary atresia, and aortopulmonary
      collaterals. RESULTS: The patient underwent a successful laparoscopic resection
      of a functioning 7-cm paraganglioma after careful preoperative preparation and
      intraoperative monitoring. Pathology returned as a well-defined, partially
      hemorrhagic mass measuring 7.0 * 4.5 * 4.5 cm adjacent to and compressing the
      adrenal gland. CONCLUSION: Surgical resection of paraganglioma tumors in rare
      patients such as this one is appropriate; however, surgery requires meticulous
      perioperative management with a multidisciplinary approach. Future studies are
      needed to determine whether there is a link between neuroendocrine tumors and
      cyanotic congenital heart disease.

PMID- 23150682
TI  - Association of postburn fatty acids and triglycerides with clinical outcome in
      severely burned children.
AB  - CONTEXT: Free fatty acids (FFAs) and triglycerides (TGs) are altered postburn,
      but whether these alterations are associated with postburn outcomes is not clear.
      OBJECTIVE: The aim of the present study was to analyze lipid metabolic profiles
      in pediatric burn patients and to correlate these profiles with patient outcomes
      and hospital courses. DESIGN AND SETTING: We conducted a prospective cohort study
      at an academic pediatric hospital burn center. PATIENTS: Our study included 219
      pediatric burn patients. MAIN OUTCOME MEASURES: Patients were stratified
      according to their plasma TG and FFA levels. Main patient outcomes, such as
      postburn morbidity and mortality, and clinical metabolic markers were analyzed.
      RESULTS: All groups were similar in demographics and injury characteristics.
      Patients with elevated TGs had significantly worse clinical outcomes associated
      with increased acute-phase protein synthesis indicating augmented inflammation
      and hypermetabolism, whereas increased FFAs did not seem to profoundly alter
      postburn outcomes. CONCLUSIONS: Elevated TGs, but not FFAs, postburn are
      associated with worsened organ function and clinical outcomes.

PMID- 23150683
TI  - A retrospective cohort analysis of the efficacy of adjuvant radiotherapy after
      primary surgical resection in patients with adrenocortical carcinoma.
AB  - CONTEXT: Adrenocortical carcinoma (ACC) is a rare malignancy with high recurrence
      and mortality rates. The role of adjuvant radiation therapy (RT) to improve
      outcome remains unclear. OBJECTIVE: The aim of this study was to evaluate the
      impact of adjuvant RT on overall survival and recurrence rates of ACC patients.
      DESIGN: We conducted a retrospective cohort study of select ACC patients who were
      seen at The University of Texas MD Anderson Cancer Center (MDACC) between 1998
      and 2011. All patients in this study underwent primary tumor resection and
      received adjuvant RT within 3 months of primary surgical resection prior to
      referral to the MDACC. We compared patients who had surgery and adjuvant RT with
      patients who had surgery alone. RESULTS: Baseline characteristics and adjuvant
      mitotane use were not significantly different between the adjuvant RT group (n =
      16) and the non-RT group (n = 32). Local recurrence occurred in seven patients
      (43.8%) who received RT and 10 patients (31.3%) in the control group. At 5 yr,
      the estimated local recurrence-free rate (95% confidence interval) was 53% (32
      87%) in the RT group and 67% (52-86%) in the non-RT group (P = 0.53). The
      distributions of time to distant recurrence and recurrence-free survival were not
      significantly different between the two groups. Using a multivariate Cox
      proportional hazards model for overall survival, the hazard ratio for RT use was
      1.593 (95% confidence interval, 0.707-3.589; P = 0.26) after adjusting for stage
      and adjuvant mitotane therapy. CONCLUSIONS: ACC has high rates of recurrence. In
      our study, RT did not improve clinical outcomes in patients who received their
      initial care in the community. We believe there is a need for a collaborative,
      multicenter, prospective randomized trial to evaluate the role of adjuvant
      treatments (both mitotane and RT) to assess their impact on recurrence patterns
      and survival.

PMID- 23150684
TI  - NGAL controls the metastatic potential of anaplastic thyroid carcinoma cells.
AB  - CONTEXT: We have previously identified neutrophil gelatinase-associated lipocalin
      (NGAL) as one of the genes mediating the oncogenic activity of nuclear factor
      kappaB in human anaplastic thyroid carcinomas (ATCs). OBJECTIVES: To further
      investigate the role of NGAL in thyroid cancer, we established NGAL knocked-down
      and NGAL overexpressing ATC cell lines. RESULTS: We found that the ability of
      NGAL knocked-down cells to degrade Matrigel in a transwell invasion assay and to
      form lung metastasis in nude mice was decreased. Because NGAL binds matrix
      metalloproteinase-9 (MMP-9), to form a macromolecular complex involved in the
      regulation of metastatic spread of cancer cells and given the strong expression
      of both genes in tissue specimens from human ATCs, we analyzed the MMP-9
      enzymatic activity in NGAL-null ATC cells. Enzymatic immunoassays show that MMP-9
      activity is reduced in NGAL-null ATC cells, even if its expression is not
      affected by NGAL inhibition. Ectopic expression of NGAL in an ATC cell line not
      expressing NGAL determines an increase of its metastatic property. The use of a
      mutated form of NGAL, unable to bind MMP-9, has no positive effect on the
      invasive potential of ATC cells and does not improve the MMP-9 enzymatic
      activity. CONCLUSIONS: Our results indicate NGAL as a novel target of nuclear
      factor-kappaB prometastatic activity in thyroid cancer through enhancement of MMP
      9 enzymatic activity.

PMID- 23150685
TI  - Mild cold exposure modulates fibroblast growth factor 21 (FGF21) diurnal rhythm
      in humans: relationship between FGF21 levels, lipolysis, and cold-induced
      thermogenesis.
AB  - CONTEXT: Cold exposure stimulates fibroblast growth factor 21 (FGF21) secretion
      in animals, enhancing the cold-induced thermogenesis (CIT) response through
      browning of white adipose tissue. In humans, the effects of cold exposure on
      circulating FGF21 levels are unknown. OBJECTIVE: Our objective was to evaluate
      the effects of mild cold exposure on circulating FGF21 and its relationship with
      CIT and lipolysis in humans. DESIGN AND SETTING: We conducted a randomized,
      single-blind, crossover intervention study at the National Institutes of Health
      Clinical Center. PARTICIPANTS: Participants were healthy adults. INTERVENTION:
      Subjects were exposed to a 12-h exposure to 24 or 19 C in a whole-room indirect
      calorimeter. OUTCOME MEASURES: Energy expenditure, plasma FGF 21, nonesterified
      fatty acid, and adipose tissue microdialysis glycerol concentrations were
      evaluated. RESULTS: At 24 C, plasma FGF21 exhibited a diurnal rhythm, peaking at
      0800 h [110 (59-178) pg/ml], and progressively dropped to a nadir at 1700 h [41
      (21-71) pg/ml, P < 0.0001] before rising at 1900 h [60 (11-81) pg/ml, P <
      0.0001]. Exposure at 19 C lessened the diurnal reduction of FGF21 observed at 24
      C from 0800-1700 h and augmented overall FGF21 levels by 37 +/- 45% (P = 0.01).
      The change in area under the curve plasma FGF21 between 19 and 24 C correlated
      positively with the change in area under the curve adipose microdialysate
      glycerol (R(2) = 0.35, P = 0.04) but not with nonesterified fatty acid. Cold
      induced increase in FGF21 predicted greater rise in energy expenditure during
      cold exposure (beta = 0.66, P = 0.027), independent of age, gender, fat mass, and
      lean mass. CONCLUSIONS: Mild cold exposure increased circulating FGF21 levels,
      predicting greater lipolysis and CIT. A small reduction in environmental
      temperature is sufficient to modulate FGF21 diurnal rhythm in humans, which may
      mediate cold-induced metabolic changes similar to those in animals.

PMID- 23150686
TI  - Diurnal cortisol changes in newborn infants suggesting entrainment of peripheral
      circadian clock in utero and at birth.
AB  - BACKGROUND: In the rodent and human fetus, a diurnal cortisol rhythm is observed
      that is entrained in antiphase to the maternal rhythm. However, after birth, the
      adrenal circadian rhythm becomes unsynchronized with the clock time, and an adult
      type, 24-h rhythm is observed only after a few months. Little is known about when
      and how the fetal adrenal circadian rhythm is synchronized with the day-night
      cycle. METHODS: To investigate the function of adrenal circadian clock in the
      newborn infant, eight serial saliva samples were collected every 3 h over 24 h
      (starting at 0900 h) in 27 newborn infants. RESULTS: Cortisol levels were higher
      during the period 1500 to earlier than 2100 h than during 0900 to earlier than
      1500 h and 0300 to earlier than 0900 h (both P < 0.05). Salivary cortisol levels
      collected during 0 to <6, 6 to <12, and 12 to <18 hours after the clock time at
      birth (birth time) were higher than those collected during 18 to <24 hours after
      the birth time (P < 0.005, 0.05, and 0.05, respectively). The acrophase of
      salivary cortisol was linearly correlated with the birth time within the first 5
      d of life (P < 0.005) but not thereafter. CONCLUSION: In the newborn infant,
      diurnal increase in cortisol was observed in the late afternoon and in
      correspondence with the birth time. The adrenal circadian rhythm acquired in
      utero may be reentrained by endocrinological events at birth. Such complex
      regulation of the adrenal circadian clock may inhibit a swift synchronization of
      the circadian clock to the day-night rhythm.

PMID- 23150687
TI  - Life expectancy is reduced in differentiated thyroid cancer patients >= 45 years
      old with extensive local tumor invasion, lateral lymph node, or distant
      metastases at diagnosis and normal in all other DTC patients.
AB  - OBJECTIVE: Differentiated thyroid carcinoma (DTC) generally has a good prognosis.
      As yet, however, it is unclear whether life expectancy is reduced in these
      patients and, if so, to what extent. The aim of this study was to determine how
      the all-cause mortality rate in DTC patients compares to that of the general
      population. DESIGN: A prospective database study was conducted. PATIENTS: The
      study included 2011 DTC patients treated in our hospital from 1980-2011. All
      patients received total thyroidectomy with subsequent (131)I ablation, except for
      those with an isolated papillary microcarcinoma. Survival data for the general
      German population were obtained from the German Federal Statistics Agency and
      matched to our DTC population for age and sex. RESULTS: Patients who were at
      least 45 yr old at diagnosis and had extensive perithyroidal invasion (UICC/AJCC
      TNM system, 7th edition, stages IVa and IVb), lateral cervical lymph node
      metastases (TNM stage IVa), or distant metastases (TNM stage IVc) showed a
      clearly reduced life expectancy [relative cumulative survival rate
      (observed:expected) for stage IVc after 20 yr, 0.295; 95% confidence interval,
      0.033-0.556]. In patients over 60 yr of age at diagnosis, the loss of life
      expectancy was (much) greater than for those aged 45-59 yr in all groups. Life
      expectancy was not reduced in patients with TNM stages I, II, or III (86% of
      patients). CONCLUSION: Life expectancy is not significantly reduced in 86% of DTC
      patients; only patients at least 45 yr old with extensive local invasion, lateral
      lymph node metastases, and/or distant metastases (TNM stages IVa, IVb, and IVc)
      at diagnosis showed a clearly lower life expectancy.

PMID- 23150688
TI  - A comparison of the use of urinary cortisol to creatinine ratios and nocturnal
      salivary cortisol in the evaluation of cyclicity in patients with Cushing's
      syndrome.
AB  - CONTEXT: Cyclical Cushing's syndrome is detected in our center by collecting
      sequential early morning urine (EMU) samples for cortisol to creatinine ratio
      over 28 d. The Endocrine Society suggests that nocturnal salivary cortisol (NSC)
      may be used to assess patients for cyclical Cushing's. However, there is only
      very limited evidence that it correlates with EMU testing or that it demonstrates
      cycling over 28 d. OBJECTIVE: We sought to correlate NSC with EMU results
      collected the following morning and to determine whether NSC could be used to
      detect cyclical Cushing's. DESIGN AND SETTING: An observation study of 28-d
      collections for NSC and EMU was performed in a tertiary referral center over 1
      yr. PATIENTS: A 28-d collection of NSC and EMU was performed in 10 patients with
      confirmed or suspected Cushing's syndrome. MAIN OUTCOME MEASURE: The main outcome
      of the study was the correlation of salivary and urinary cortisol with graphical
      assessment of results for cycling. RESULTS: Eleven collections were performed.
      One patient with cyclical Cushing's completed the collection before and after
      cabergoline therapy. Two hundred seventy matched salivary and urinary results
      were correlated (r = 0.79; P < 0.001). In two patients with cyclical Cushing's,
      EMU and NSC followed a similar cyclical pattern. In one patient with recurrent
      cyclical Cushing's, cortisol was elevated in both saliva and urine but with more
      prominent cycles in saliva. CONCLUSION: NSC correlated well with EMU. NSC
      detected all cases of cyclical Cushing's. Therefore, NSC may prove to be an
      additional option or replacement for EMU in detecting cyclical Cushing's
      syndrome.

PMID- 23150689
TI  - Distinct developmental signatures of human abdominal and gluteal subcutaneous
      adipose tissue depots.
AB  - CONTEXT: Fat distribution differs in men and women, but in both sexes, a
      predominantly gluteal-femoral compared with abdominal (central) fat distribution
      is associated with lower metabolic risk. Differences in cellular characteristics
      and metabolic functions of these depots have been described, but the molecular
      mechanisms involved are not understood. OBJECTIVE: Our objective was to identify
      depot- and sex-dependent differences in gene expression in human abdominal and
      gluteal sc adipose tissues. DESIGN AND METHODS: Abdominal and gluteal adipose
      tissue aspirates were obtained from 14 premenopausal women [age 27.5 +/- 7.0 yr,
      body mass index (BMI) 27.3 +/- 6.2 kg/m(2), and waist-to-hip ratio 0.82 +/- 0.04]
      and 21 men (age 29.7+/-7.4 yr, BMI 27.2 +/- 4.5 kg/m(2), and waist-to-hip ratio
      0.91 +/- 0.07) and transcriptomes were analyzed using Illumina microarrays.
      Expression of selected genes was determined in isolated adipocytes and stromal
      vascular fractions from each depot, and in in vitro cultures before and after
      adipogenic differentiation. RESULTS: A total of 284 genes were differentially
      expressed between the abdominal and gluteal depot, either specifically in males
      (n = 66) or females (n = 159) or in both sexes (n = 59). Most notably, gene
      ontology and pathway analysis identified homeobox genes (HOXA2, HOXA3, HOXA4,
      HOXA5, HOXA9, HOXB7, HOXB8, HOXC8, and IRX2) that were down-regulated in the
      gluteal depot in both sexes (P = 2 * 10(-10)). Conversely, HOXA10 was up
      regulated in gluteal tissue and HOXC13 was detected exclusively in this depot.
      These differences were independent of BMI, were present in both adipocytes and
      stromal vascular fractions of adipose tissue, and were retained throughout in
      vitro differentiation. CONCLUSIONS: We conclude that developmentally programmed
      differences may contribute to the distinct phenotypic characteristics of
      peripheral fat.

PMID- 23150690
TI  - Low levels of serum 25-hydroxyvitamin D are associated with increased risk of
      myocardial infarction, especially in women: results from the MONICA/KORA Augsburg
      case-cohort study.
AB  - CONTEXT AND OBJECTIVE: A growing body of evidence suggests that vitamin D
      deficiency may adversely affect the cardiovascular system. Therefore, we thought
      to prospectively assess the association between serum 25-hydroxyvitamin D, the
      most commonly used index of vitamin D status, and incident coronary heart
      disease. DESIGN, SETTING, AND PATIENTS: We measured serum levels of 25[OH]D in
      1783 healthy middle-aged subjects (964 men, 819 women) in the population-based
      Monitoring of Trends and Determinants in Cardiovascular Disease/Cooperative
      Health Research in the Region of Augsburg studies. A total of 298 coronary heart
      disease cases were identified over a mean follow-up period of 11 yr. RESULTS:
      After adjustment for age, survey, and season of blood sampling, the hazard ratio
      (HR) and 95% confidence interval comparing tertile extremes of serum levels of
      25[OH]D was 0.32 (0.16-0.65) (P for trend = 0.001) in women and 0.56 (0.38-0.82)
      (P for trend = 0.005) in men. Further adjustment for traditional cardiovascular
      risk factors slightly attenuated the association in women [HR 0.39 (0.18-0.84); P
      for trend = 0.013], whereas it became nonsignificant in men [HR 0.76 (0.49-1.17);
      P for trend = 0.215]. After additional adjustment for C-reactive protein, IL-6,
      soluble intercellular adhesion molecule-1, and interferon-gamma-inducible protein
      10, the association still remained significant in women [HR 0.42 (0.19-0.93); P
      for trend = 0.028], and it was further reduced in men [HR 0.84 (0.52-1.35); P for
      trend = 0.461]. CONCLUSION: Our findings suggest that higher vitamin D levels are
      associated with decreased risk of coronary heart disease. This effect is more
      pronounced in women than in men. Further clinical and experimental studies are
      needed to investigate the sex differences and whether vitamin D supplementation
      could contribute to the prevention of coronary heart disease.

PMID- 23150692
TI  - Diabetes and risk of hearing impairment in adults: a meta-analysis.
AB  - CONTEXT: Recently, several studies have investigated the relationship between
      diabetes and hearing impairment, but results were inconsistent. OBJECTIVE: Our
      objective was to compare the prevalence of hearing impairment between diabetic
      and nondiabetic adults. DATA SOURCES: We performed a systematic literature search
      using MEDLINE (1950 to May 30, 2011) and EMBASE (1974 to May 30, 2011). STUDY
      SELECTION: Cross-sectional studies were included if data on numbers of hearing
      impaired and non-hearing-impaired cases with diabetes were presented. Hearing
      impairment was limited to that assessed by pure-tone audiometry that included at
      least 2 kHz of frequency range and was defined as progressive, chronic,
      sensorineural, or without specified cause. DATA EXTRACTION: Two authors
      independently extracted relevant data. Odd ratios (ORs) of hearing impairment
      related to diabetes calculated in each study were pooled with the random-effects
      model. DATA SYNTHESIS: Data were obtained from 13 eligible studies (20,194
      participants and 7,377 cases). Overall pooled OR (95% confidence interval) of
      hearing impairment for diabetic participants compared with nondiabetic
      participants was 2.15 (1.72-2.68). OR was higher in younger participants (mean
      age, <=60 yr) than in those over 60 yr among which the OR remained significant
      (2.61 and 1.58, P = 0.008). The strength of the association between diabetes and
      prevalence of hearing impairment was not significantly influenced by whether
      participants were matched for age and gender (P = 0.68) or whether participants
      chronically exposed to noisy environments were excluded (P = 0.19). CONCLUSIONS:
      Current meta-analysis suggests that the higher prevalence of hearing impairment
      in diabetic patients compared with nondiabetic patients was consistent regardless
      of age.

PMID- 23150691
TI  - The role of surgery in the management of recurrent adrenocortical carcinoma.
AB  - CONTEXT: Surgery is the standard of care for localized adrenocortical carcinomas,
      but its role for recurrent disease is not well defined. OBJECTIVE: Our objective
      was to evaluate clinical outcome after surgery for recurrence. DESIGN: We
      conducted a retrospective analysis in 154 patients with first recurrence after
      initial radical resection from the German Adrenocortical Carcinoma Registry. MAIN
      OUTCOME MEASURES: We evaluated progression-free survival (PFS) and overall
      survival (OS) by Kaplan-Meier method and identified prognostic factors by Cox
      regression analysis. RESULT: A total of 101 patients underwent repeated surgery
      (radical resection, n = 78), and 99 received (additional) nonsurgical therapy.
      After a median of 6 (1-221) months, 144 patients (94%) experienced progression.
      Multivariate analysis adjusted for age, sex, tumor burden, time to first
      recurrence (TTFR), surgery for recurrence (including resection status), and
      additional therapy indicated that only two factors were significantly associated
      with shorter PFS [hazard ratio for progression: for TTFR <= 12 months, 1.8 (95%
      confidence interval = 1.3-2.6) vs. TTFR > 12 months; for macroscopically
      incomplete resection, 3.4 (1.5-7.9), and for no surgery, 3.4 (1.6-7.0) vs.
      microscopically complete (R0)-resection and OS [hazard ratio for death: for TTFR
      > 12 months, 3.1 (2.0-4.7) vs. TTFR <= 12 months; for macroscopically incomplete
      resection, 2.7 (1.1-6.9), and no surgery, 4.2 (1.8-9.6) vs. R0-resection].
      Patients who had both TTFR over 12 months and R0-resection of recurrent tumors (n
      = 22) had the best prognosis (median PFS, 24 months; median OS, >60 months).
      CONCLUSIONS: The best predictors of prolonged survival after first recurrence are
      TTFR over 12 months and R0-resection. Our data suggest that patients with longer
      TTFR and tumors amenable to radical resection should be operated, whereas
      individualized treatment decisions are needed for patients with short TTFR or
      with not completely resectable tumors.

PMID- 23150693
TI  - Higher mitochondrial respiration and uncoupling with reduced electron transport
      chain content in vivo in muscle of sedentary versus active subjects.
AB  - OBJECTIVE: This study investigated the disparity between muscle metabolic rate
      and mitochondrial metabolism in human muscle of sedentary vs. active individuals.
      RESEARCH DESIGN AND METHODS: Chronic activity level was characterized by a
      physical activity questionnaire and a triaxial accelerometer as well as a maximal
      oxygen uptake test. The ATP and O(2) fluxes and mitochondrial coupling (ATP/O(2)
      or P/O) in resting muscle as well as mitochondrial capacity (ATP(max)) were
      determined in vivo in human vastus lateralis muscle using magnetic resonance and
      optical spectroscopy on 24 sedentary and seven active subjects. Muscle biopsies
      were analyzed for electron transport chain content (using complex III as a
      representative marker) and mitochondrial proteins associated with antioxidant
      protection. RESULTS: Sedentary muscle had lower electron transport chain complex
      content (65% of the active group) in proportion to the reduction in ATP(max)
      (0.69 +/- 0.07 vs. 1.07 +/- 0.06 mM sec(-1)) as compared with active subjects.
      This lower ATP(max) paired with an unchanged O(2) flux in resting muscle between
      groups resulted in a doubling of O(2) flux per ATP(max) (3.3 +/- 0.3 vs. 1.7 +/-
      0.2 MUM O(2) per mM ATP) that reflected mitochondrial uncoupling (P/O = 1.41 +/-
      0.1 vs. 2.1 +/- 0.3) and greater UCP3/complex III (6.0 +/- 0.7 vs. 3.8 +/- 0.3)
      in sedentary vs. active subjects. CONCLUSION: A smaller mitochondrial pool
      serving the same O(2) flux resulted in elevated mitochondrial respiration in
      sedentary muscle. In addition, uncoupling contributed to this higher
      mitochondrial respiration. This finding resolves the paradox of stable muscle
      metabolism but greater mitochondrial respiration in muscle of inactive vs. active
      subjects.

PMID- 23150694
TI  - Maternal thyroid hormone parameters during early pregnancy and birth weight: the
      Generation R Study.
AB  - CONTEXT: Maternal hyperthyroidism during pregnancy is associated with an
      increased risk of low birth weight, predisposing to neonatal morbidity and
      mortality. However, the effects of variation in maternal serum thyroid parameters
      within the normal range on birth weight are largely unknown. OBJECTIVE: The aim
      was to study the effects of early pregnancy maternal serum thyroid parameters
      within the normal range on birth weight, as well as the relation between
      umbilical cord thyroid parameters and birth weight. DESIGN, SETTING, AND
      PARTICIPANTS: In early pregnancy, serum TSH, FT4 (free T(4)), and thyroid
      peroxidase antibody levels were determined in 4464 pregnant women. Cord serum TSH
      and FT4 levels were determined in 2724 newborns. Small size for gestational age
      at birth (SGA) was defined as a gestational age-adjusted birth weight below the
      2.5th percentile. The associations between normal-range maternal and cord thyroid
      parameters, birth weight, and SGA were studied using regression analyses.
      RESULTS: In mothers with normal-range FT4 and TSH levels, higher maternal FT4
      levels were associated with lower birth weight [beta = -15.4 (3.6) g/pmol .
      liter, mean (SE); P = 1.6 * 10(-5)], as well as with an increased risk of SGA
      newborns [odds ratio (95% confidence interval) = 1.09 (1.01-1.17); P = 0.03].
      Birth weight was positively associated with both cord TSH [beta = 4.1 (1.4) g/mU
      . liter; P = 0.007] and FT4 levels [beta = 23.0 (3.2) g/pmol . liter; P = 9.2 *
      10(-13)]. CONCLUSIONS: We show that maternal high-normal FT4 levels in early
      pregnancy are associated with lower birth weight and an increased risk of SGA
      newborns. Additionally, birth weight is positively associated with cord TSH and
      FT4 levels. These data demonstrate that even mild variation in thyroid function
      within the normal range can have important fetal consequences.

PMID- 23150695
TI  - Percutaneous ultrasound-guided laser ablation is effective for treating selected
      nodal metastases in papillary thyroid cancer.
AB  - CONTEXT: Mini-invasive procedures may be useful for control of local neck nodal
      metastases of papillary thyroid cancer (PTC) in high-risk patients. OBJECTIVE:
      Our objective was to assess the effectiveness and safety of ultrasound (US)
      guided laser ablation (LA) for nonsurgical treatment of small-size neck
      metastases of PTC. DESIGN AND SETTING: We conducted a pilot study on a surgically
      controlled metastasis, followed by a prospective trial with a 12-month follow-up.
      PARTICIPANTS: Participants included five patients with previous total
      thyroidectomy and neck dissection for PTC, with eight new lymph node metastases
      in an area already treated with surgical dissection and lymph node volume less
      than 2 ml and absent radioiodine uptake. OUTCOME MEASURES: We evaluated
      thyroglobulin (Tg) and US changes of the lymph nodes 6 and 12 months after LA as
      well as tolerability and side effects of the procedure. RESULTS: A single LA
      treatment induced progressive volume reduction of the eight metastatic lymph
      nodes. Mean baseline volume decreased from 0.64 +/- 0.58 to 0.07 +/- 0.06 ml at
      12-month control. Mean volume reduction was 64.4 +/- 0.19% at 6 months (P < 0.02
      vs. baseline) and 87.7 +/- 0.11% at 12 months (P < 0.01 vs. baseline). No
      regrowth was registered. Mean serum Tg on LT4 decreased from 8.0 +/- 3.2 ng/ml to
      2.0 +/- 2.5 ng/ml at 12-month control (P < 0.02 vs baseline). In three patients
      (60%) Tg levels were undetectable at 12-month control. Pain was tolerable in two
      cases and mild in three cases. Transient dysphonia in one patient was the only
      complication. After 1 yr, no cancer seeding was present. CONCLUSION: LA is a well
      tolerated outpatient procedure that results in a rapid cytoreduction of cervical
      nodal metastases of PTC. Mini-invasive procedures may be used in lieu of surgery
      as an adjunctive therapy for small-burden local/regional disease recurrence. They
      are occasionally associated with an anatomical or biochemical cure, but long-term
      follow-up or controlled trials are needed.

PMID- 23150696
TI  - Hodgkin lymphoma: protecting the victims of our success.

PMID- 23150697
TI  - Risk of venous thromboembolism in patients with cancer treated with Cisplatin: a
      systematic review and meta-analysis.
AB  - PURPOSE: Several reports suggest that cisplatin is associated with an increased
      risk of thromboembolism. However, because the excess risk of venous
      thromboembolic events (VTEs) with cisplatin-based chemotherapy has not been well
      described, we conducted a systemic review and meta-analysis of randomized
      controlled trials evaluating the incidence and risk of VTEs associated with
      cisplatin-based chemotherapy. METHODS: PubMed was searched for articles published
      from January 1, 1990, to December 31, 2010. Eligible studies included prospective
      randomized phase II and III trials evaluating cisplatin-based versus non
      cisplatin-based chemotherapy in patients with solid tumors. Data on all-grade
      VTEs were extracted. Study quality was calculated using Jadad scores. Incidence
      rates, relative risks (RRs), and 95% CIs were calculated using a random effects
      model. RESULTS: A total of 8,216 patients with various advanced solid tumors from
      38 randomized controlled trials were included. The incidence of VTEs was 1.92%
      (95% CI, 1.07 to 2.76) in patients treated with cisplatin-based chemotherapy and
      0.79% (95% CI, 0.45 to 1.13) in patients treated with non-cisplatin-based
      regimens. Patients receiving cisplatin-based chemotherapy had a significantly
      increased risk of VTEs (RR, 1.67; 95% CI, 1.25 to 2.23; P = .01). Exploratory
      subgroup analysis revealed the highest RR of VTEs in patients receiving a weekly
      equivalent cisplatin dose > 30 mg/m(2) (2.71; 95% CI, 1.17 to 6.30; P = .02) and
      in trials reported during 2000 to 2010 (1.72; 95% CI, 1.27 to 2.34; P = .01).
      CONCLUSION: Cisplatin is associated with a significant increase in the risk of
      VTEs in patients with advanced solid tumors when compared with non-cisplatin
      based chemotherapy.

PMID- 23150698
TI  - Routine bone marrow biopsy has little or no therapeutic consequence for positron
      emission tomography/computed tomography-staged treatment-naive patients with
      Hodgkin lymphoma.
AB  - PURPOSE: To investigate whether bone marrow biopsy (BMB) adds useful information
      to [(18)F]fluorodeoxyglucose (FDG) positron emission tomography/computed
      tomography (PET/CT) staging in patients with Hodgkin lymphoma (HL). PATIENTS AND
      METHODS: Newly diagnosed patients with HL undergoing a pretherapeutic staging
      that encompasses both PET/CT and BMB were included in this retrospective study.
      The pattern of skeletal FDG uptake was categorized as uni-, bi-, or multifocal
      (>= three lesions). Clinical stage, risk assessment, and treatment plan were
      determined with and without the contribution of BMB results according to the Ann
      Arbor classification and the guidelines from the German Hodgkin Study Group.
      RESULTS: A total of 454 patients with HL were included of whom 82 (18%) had focal
      skeletal PET/CT lesions and 27 (6%) had positive BMB. No patients with positive
      BMB were assessed as having stage I to II disease by PET/CT staging. BMB upstaged
      five patients, assessed as being stage III before BMB; none of the 454 patients
      would have been allocated to another treatment on the basis of BMB results. Focal
      skeletal PET/CT lesions identified positive and negative BMBs with a sensitivity
      and specificity of 85% and 86%, respectively. The positive and negative
      predictive values of focal skeletal PET/CT lesions for BMB results were 28% and
      99%, respectively. CONCLUSION: A consistent finding of this study was the absence
      of positive BMBs in PET/CT-assessed stage I to II disease. The omission of
      staging BMB would not have changed the risk assessment or treatment strategy in
      this cohort of 454 newly diagnosed patients with HL.

PMID- 23150699
TI  - Procarbazine and infertility in low-grade gliomas in children.

PMID- 23150700
TI  - Associations between end-of-life discussion characteristics and care received
      near death: a prospective cohort study.
AB  - PURPOSE: National guidelines recommend that discussions about end-of-life (EOL)
      care planning happen early for patients with incurable cancer. We do not know
      whether earlier EOL discussions lead to less aggressive care near death. We
      sought to evaluate the extent to which EOL discussion characteristics, such as
      timing, involved providers, and location, are associated with the aggressiveness
      of care received near death. PATIENTS AND METHODS: We studied 1,231 patients with
      stage IV lung or colorectal cancer in the Cancer Care Outcomes Research and
      Surveillance Consortium, a population- and health system-based prospective cohort
      study, who died during the 15-month study period but survived at least 1 month.
      Our main outcome measure was the aggressiveness of EOL care received. RESULTS:
      Nearly half of patients received at least one marker of aggressive EOL care,
      including chemotherapy in the last 14 days of life (16%), intensive care unit
      care in the last 30 days of life (9%), and acute hospital-based care in the last
      30 days of life (40%). Patients who had EOL discussions with their physicians
      before the last 30 days of life were less likely to receive aggressive measures
      at EOL, including chemotherapy (P = .003), acute care (P < .001), or any
      aggressive care (P < .001). Such patients were also more likely to receive
      hospice care (P < .001) and to have hospice initiated earlier (P < .001).
      CONCLUSION: Early EOL discussions are prospectively associated with less
      aggressive care and greater use of hospice at EOL.

PMID- 23150702
TI  - Mitochondrial DNA mutation in serous ovarian cancer: implications for
      mitochondria-coded genes in chemoresistance.

PMID- 23150701
TI  - Optimal morphologic response to preoperative chemotherapy: an alternate outcome
      end point before resection of hepatic colorectal metastases.
AB  - PURPOSE: The purposes of this study were to confirm the prognostic value of an
      optimal morphologic response to preoperative chemotherapy in patients undergoing
      chemotherapy with or without bevacizumab before resection of colorectal liver
      metastases (CLM) and to identify predictors of the optimal morphologic response.
      PATIENTS AND METHODS: The study included 209 patients who underwent resection of
      CLM after preoperative chemotherapy with oxaliplatin- or irinotecan-based
      regimens with or without bevacizumab. Radiologic responses were classified as
      optimal or suboptimal according to the morphologic response criteria. Overall
      survival (OS) was determined, and prognostic factors associated with an optimal
      response were identified in multivariate analysis. RESULTS: An optimal
      morphologic response was observed in 47% of patients treated with bevacizumab and
      12% of patients treated without bevacizumab (P < .001). The 3- and 5-year OS
      rates were higher in the optimal response group (82% and 74%, respectively)
      compared with the suboptimal response group (60% and 45%, respectively; P <
      .001). On multivariate analysis, suboptimal morphologic response was an
      independent predictor of worse OS (hazard ratio, 2.09; P = .007). Receipt of
      bevacizumab (odds ratio, 6.71; P < .001) and largest metastasis before
      chemotherapy of <= 3 cm (odds ratio, 2.12; P = .025) were significantly
      associated with optimal morphologic response. The morphologic response showed no
      specific correlation with conventional size-based RECIST criteria, and it was
      superior to RECIST in predicting major pathologic response. CONCLUSION:
      Independent of preoperative chemotherapy regimen, optimal morphologic response is
      sufficiently correlated with OS to be considered a surrogate therapeutic end
      point for patients with CLM.

PMID- 23150703
TI  - Bortezomib-related diffuse alveolar hemorrhage.

PMID- 23150704
TI  - Mitomycin in anal cancer: still the standard of care.
AB  - A 52-year-old woman presents with a 2-month history of bright red blood per
      rectum. Her bleeding is associated with bowel movements and a sense of incomplete
      evacuation. She denies fecal incontinence or change in stool caliber. On digital
      rectal examination, the tumor is palpated approximately 3 cm from the anal verge,
      posterior and slightly to the right, positioned at the top of the anal canal and
      extending into the rectum, measuring approximately 2.5 cm. Additionally, a firm
      1.5-cm left-sided inguinal node is palpated. The patient is then referred for
      colonoscopy, which reveals a mass in the anal canal; biopsy of the mass shows
      squamous cell carcinoma. Positron emission tomography-computed tomography (PET
      CT) demonstrates thickening in the low rectum with [(18)F]fluorodeoxyglucose
      (FDG) avidity (Figs 1A, 1B). The left inguinal node is visualized, as is a
      perirectal lymph node with associated FDG avidity (Figs 1C, 1D). The patient is
      staged as having T2N3 squamous cell carcinoma of the anal canal (Table 1). Her
      medical history is otherwise unremarkable, including for HIV, prior abnormal
      Papanicolaou smears, and other risk factors for human papillomavirus (HPV)
      exposure.

PMID- 23150705
TI  - RET fusion genes in non-small-cell lung cancer.

PMID- 23150706
TI  - RET fusions define a unique molecular and clinicopathologic subtype of non-small
      cell lung cancer.
AB  - PURPOSE: The RET fusion gene has been recently described in a subset of non-small
      cell lung cancers (NSCLCs). Because we have limited knowledge about these tumors,
      this study was aimed at determining the clinicopathologic characteristics of
      patients with NSCLC harboring the RET fusion gene. PATIENTS AND METHODS: We
      examined the RET fusion gene in 936 patients with surgically resected NSCLC using
      a reverse transcriptase polymerase chain reaction (PCR) plus quantitative real
      time PCR strategy, with validation using immunohistochemical and fluorescent in
      situ hybridization assays. A subset of 633 lung adenocarcinomas was also studied
      for EGFR, KRAS, HER2, and BRAF mutations, as well as ALK rearrangements. Patient
      characteristics, including age, sex, smoking history, stage, grade, International
      Association for the Study of Lung Cancer/American Thoracic Society/European
      Respiratory Society classification of subtypes of lung adenocarcinoma, and
      relapse-free survival, were collected. RESULTS: Of 936 patients with NSCLC, the
      RET fusion gene was exclusively detected in 13 patients (11 of 633 patients with
      adenocarcinomas and two of 24 patients with adenosquamous cell carcinomas). Of
      the 13 patients, nine patients had KIF5B-RET, three patients had CCDC6-RET, and
      one patient had a novel NCOA4-RET fusion. Patients with lung adenocarcinomas with
      RET fusion gene had more poorly differentiated tumors (63.6%; P = .029 for RET v
      ALK, P = .007 for RET v EGFR), with a tendency to be younger (<= 60 years; 72.7%)
      and never-smokers (81.8%) and to have solid subtype (63.6%) and a smaller tumor
      (<= 3 cm) with N2 disease (54.4%). The median relapse-free survival was 20.9
      months. CONCLUSION: RET fusion occurs in 1.4% of NSCLCs and 1.7% of lung
      adenocarcinomas and has identifiable clinicopathologic characteristics,
      warranting further clinical consideration and targeted therapy investigation.

PMID- 23150708
TI  - Primary follicular lymphoma of the GI tract: an increasingly recognized entity.

PMID- 23150707
TI  - Long-term update of US GI intergroup RTOG 98-11 phase III trial for anal
      carcinoma: survival, relapse, and colostomy failure with concurrent
      chemoradiation involving fluorouracil/mitomycin versus fluorouracil/cisplatin.
AB  - PURPOSE: On initial publication of GI Intergroup Radiation Therapy Oncology Group
      (RTOG) 98-11 [A Phase III Randomized Study of 5-Fluorouracil (5-FU), Mitomycin,
      and Radiotherapy Versus 5-Fluorouracil, Cisplatin and Radiotherapy in Carcinoma
      of the Anal Canal], concurrent chemoradiation (CCR) with fluorouracil (FU) plus
      mitomycin (MMC) decreased colostomy failure (CF) when compared with induction
      plus concurrent FU plus cisplatin (CDDP), but did not significantly impact
      disease-free survival (DFS) or overall survival (OS) for anal canal carcinoma.
      The intent of the updated analysis was to determine the long-term impact of
      treatment on survival (DFS, OS, colostomy-free survival [CFS]), CF, and relapse
      (locoregional failure [LRF], distant metastasis) in this patient group. PATIENTS
      AND METHODS: Stratification factors included sex, clinical node status, and
      primary size. DFS and OS were estimated univariately by the Kaplan-Meier method,
      and treatment arms were compared by log-rank test. Time to relapse and CF were
      estimated by the cumulative incidence method and treatment arms were compared by
      using Gray's test. Multivariate analyses used Cox proportional hazard models to
      test for treatment differences after adjusting for stratification factors.
      RESULTS: Of 682 patients accrued, 649 were analyzable for outcomes. DFS and OS
      were statistically better for RT + FU/MMC versus RT + FU/CDDP (5-year DFS, 67.8%
      v 57.8%; P = .006; 5-year OS, 78.3% v 70.7%; P = .026). There was a trend toward
      statistical significance for CFS (P = .05), LRF (P = .087), and CF (P = .074).
      Multivariate analysis was statistically significant for treatment and clinical
      node status for both DFS and OS, for tumor diameter for DFS, and for sex for OS.
      CONCLUSION: CCR with FU/MMC has a statistically significant, clinically
      meaningful impact on DFS and OS versus induction plus concurrent FU/CDDP, and it
      has borderline significance for CFS, CF, and LRF. Therefore, RT + FU/MMC remains
      the preferred standard of care.

PMID- 23150709
TI  - Gonadal function and fertility in survivors after Hodgkin lymphoma treatment
      within the German Hodgkin Study Group HD13 to HD15 trials.
AB  - PURPOSE: To optimize fertility advice in patients with Hodgkin lymphoma (HL)
      before therapy and during survivorship, information on the impact of chemotherapy
      is needed. Therefore, we analyzed gonadal functions in survivors of HL. PATIENTS
      AND METHODS: Women younger than age 40 and men younger than 50 years at diagnosis
      in ongoing remission at least 1 year after therapy within the German Hodgkin
      Study Group HD13 to HD15 trials for early- and advanced-stage HL were included.
      Hormone parameters, menstrual cycle, symptoms of hypogonadism, and offspring were
      evaluated. RESULTS: A total of 1,323 (55%) of 2,412 contacted female and male
      survivors were evaluable for the current analysis (mean follow-up, 46 and 48
      months, respectively). Follicle-stimulating hormone, anti-Mullerian hormone, and
      inhibin B levels correlated significantly with therapy intensity (P < .001). Low
      birth rates were observed in survivors after advanced-stage treatment within the
      observation time (women, 6.5%; men, 3.3%). Regular menstrual cycle was reported
      by more than 90% of female survivors of early-stage HL (recovery time mostly <=
      12 months). After six to eight cycles of bleomycin, etoposide, doxorubicin,
      cyclophosphamide, vincristine, procarbazine, and prednisone, menstrual activity
      was strongly related to age (< v >= 30 years: 82% v 45%, respectively; P < .001;
      prolonged recovery time). Thirty-four percent of women age >= 30 years suffered
      severe menopausal symptoms (three- to four-fold more frequently than expected).
      In contrast, male survivors had mean levels of testosterone within the normal
      range and reported no increased symptoms of hypogonadism. CONCLUSION: The present
      analysis in a large group of survivors of HL provides well-grounded information
      on gonadal toxicity of currently used treatment regimens and allows risk-adapted
      fertility preservation and comprehensive support during therapy and follow-up.

PMID- 23150712
TI  - Antibody C region influences TGN1412-like functional activity in vitro.
AB  - The unexpected outcome of the clinical trial of the superagonistic CD28 mAb
      TGN1412 (IgG4kappa) continues to stimulate interest. We show that TGN1412 binds
      similarly to human and cynomolgus macaque FcgammaR, eliminating the possibility
      that differences in Fc-mediated interactions with FcgammaR contributed to the
      failure of preclinical testing in macaques to predict toxicity in humans. The
      influence of the Fc domain and C region structure on the in vitro functional
      activity of TGN1412 was investigated using F(ab')(2) and Fab fragments derived
      from TGN1412 recovered from the trial and recombinant TGN1412 subclass variants
      and mutants. Superagonistic activity, as measured by cytokine release and
      proliferation, was assessed by exposing PBMCs to immobilized mAbs/fragments or to
      aqueous mAbs/fragments in the presence of HUVEC monolayers. Removing the Fc
      generally curtailed or abolished PBMC activation. However, eliminating detectable
      FcgammaR-binding of the IgG4 by mutation (L235E) did not abrogate activity.
      Stabilizing the "wild-type" IgG4 hinge (S228P) enhanced activity without
      increasing FcgammaR binding, which could only partially be explained by
      inhibition of Fab arm-exchange. Subclass switching the IgG4 mAb to IgG1 decreased
      activity, whereas switching to IgG2 markedly increased activity. We conclude that
      the C region strongly influences in vitro CD28-mediated superagonistic signaling.
      Superagonism requires an intact Fc, as shown by the absence of activity of
      TGN1412 Fab and F(ab')(2) fragments, but, notably, appears to be relatively
      independent of FcgammaR-binding properties. We propose that the Fc, potentially
      through restricting flexibility, maintains a favorable V region conformation to
      allow superagonistic activity. These findings have important implications for Ab
      design strategies.

PMID- 23150713
TI  - Serum-derived plasminogen is activated by apoptotic cells and promotes their
      phagocytic clearance.
AB  - The elimination of apoptotic cells, called efferocytosis, is fundamentally
      important for tissue homeostasis and prevents the onset of inflammation and
      autoimmunity. Serum proteins are known to assist in this complex process. In the
      current study, we performed a multistep chromatographic fractionation of human
      serum and identified plasminogen, a protein involved in fibrinolysis, wound
      healing, and tissue remodeling, as a novel serum-derived factor promoting
      apoptotic cell removal. Even at levels significantly lower than its serum
      concentration, purified plasminogen strongly enhanced apoptotic prey cell
      internalization by macrophages. Plasminogen acted mainly on prey cells, whereas
      on macrophages no enhancement of the engulfment process was observed. We further
      demonstrate that the efferocytosis-promoting activity essentially required the
      proteolytic activation of plasminogen and was completely abrogated by the
      urokinase plasminogen activator inhibitor-1 and serine protease inhibitor
      aprotinin. Thus, our study assigns a new function to plasminogen and plasmin in
      apoptotic cell clearance.

PMID- 23150715
TI  - Cutting edge: FcgammaRIII (CD16) and FcgammaRI (CD64) are responsible for anti
      glycoprotein 75 monoclonal antibody TA99 therapy for experimental metastatic B16
      melanoma.
AB  - mAb therapy for experimental metastatic melanoma relies on activating receptors
      for the Fc portion of IgG (FcgammaR). Opposing results on the respective
      contribution of mouse FcgammaRI, FcgammaRIII, and FcgammaRIV have been reported
      using the gp75-expressing B16 melanoma and the protective anti-gp75 mAb TA99. We
      analyzed the contribution of FcgammaRs to this therapy model using bioluminescent
      measurement of lung metastases loads, novel mouse strains, and anti-FcgammaR
      blocking mAbs. We found that the TA99 mAb-mediated effects in a combination
      therapy using cyclophosphamide relied on activating FcgammaRs. The combination
      therapy, however, was not more efficient than mAb therapy alone. We demonstrate
      that FcgammaRI and, unexpectedly, FcgammaRIII contributed to TA99 mAb therapeutic
      effects, whereas FcgammaRIV did not. Therefore, FcgammaRIII and FcgammaRI are,
      together, responsible for anti-gp75 mAb therapy of B16 lung metastases. Our
      finding that mouse FcgammaRIII contributes to Ab-induced tumor reduction
      correlates with clinical data on its human functional equivalent human
      FcgammaRIIIA (CD16A).

PMID- 23150714
TI  - Cutting edge: B cells are essential for protective immunity against Salmonella
      independent of antibody secretion.
AB  - Typhoid fever and nontyphoidal bacteremia caused by Salmonella remain critical
      human health problems. B cells are required for protective immunity to
      Salmonella, but the mechanism of protection remains unclear. In this study, we
      immunized wild-type, B cell-deficient, Ab-deficient, and class-switched Ab
      deficient mice with attenuated Salmonella and examined protection against
      secondary infection. As expected, wild-type mice were protected and B cell
      deficient mice succumbed to secondary infection. Interestingly, mice with B cells
      but lacking secreted Ab or class-switched Ab had little deficiency in resistance
      to Salmonella infection. The susceptibility of B cell-deficient mice correlated
      with marked reductions in CD4 T cell IFN-gamma production after secondary
      infection. Taken together, these data suggest that the primary role of B cells in
      acquired immunity to Salmonella is via the development of protective T cell
      immunity.

PMID- 23150716
TI  - Mice deficient in ficolin, a lectin complement pathway recognition molecule, are
      susceptible to Streptococcus pneumoniae infection.
AB  - Mannose-binding lectin (MBL) and ficolin are complexed with MBL-associated serine
      proteases, key enzymes of complement activation via the lectin pathway, and act
      as soluble pattern recognition molecules in the innate immune system. Although
      numerous reports have revealed the importance of MBL in infectious diseases and
      autoimmune disorders, the role of ficolin is still unclear. To define the
      specific role of ficolin in vivo, we generated model mice deficient in ficolins.
      The ficolin A (FcnA)-deficient (Fcna(-/-)) and FcnA/ficolin B double-deficient
      (Fcna(-/-)b(-/-)) mice lacked FcnA-mediated complement activation in the sera,
      because of the absence of complexes comprising FcnA and MBL-associated serine
      proteases. When the host defense was evaluated by transnasal infection with a
      Streptococcus pneumoniae strain, which was recognized by ficolins, but not by
      MBLs, the survival rate was significantly reduced in all three ficolin-deficient
      (Fcna(-/-), Fcnb(-/-), and Fcna(-/-)b(-/-)) mice compared with wild-type mice.
      Reconstitution of the FcnA-mediated lectin pathway in vivo improved survival rate
      in Fcna(-/-) but not in Fcna(-/-)b(-/-) mice, suggesting that both FcnA and
      ficolin B are essential in defense against S. pneumoniae. These results suggest
      that ficolins play a crucial role in innate immunity against pneumococcal
      infection through the lectin complement pathway.

PMID- 23150717
TI  - B cell TLR7 expression drives anti-RNA autoantibody production and exacerbates
      disease in systemic lupus erythematosus-prone mice.
AB  - Systemic lupus erythematosus (SLE) is a chronic systemic autoimmune disease
      characterized by the production of antinuclear autoantibodies. Antinuclear
      autoantibody development is recognized as one of the initial stages of disease
      that often results in systemic inflammation, kidney disease, and death. The
      etiology is complex, but it is clear that innate pathways may play an important
      role in disease progression. Recent data have highlighted an important role for
      the TLR family, particularly TLR7, in both human disease and murine models. In
      this study, we have presented a low copy conditional TLR7 transgenic (Tg7) mouse
      strain that does not develop spontaneous autoimmunity. When we combine Tg7 with
      the Sle1 lupus susceptibility locus, the mice develop severe disease. Using the
      CD19(Cre) recombinase system, we normalized expression of TLR7 solely within the
      B cells. Using this method we demonstrated that overexpression of TLR7 within the
      B cell compartment reduces the marginal zone B cell compartment and increases B
      and T cell activation but not T follicular helper cell development. Moreover,
      this enhanced B cell TLR7 expression permits the specific development of Abs to
      RNA/protein complexes and exacerbates SLE disease.

PMID- 23150718
TI  - Regulation of allograft survival by inhibitory FcgammaRIIb signaling.
AB  - Fcgamma receptors (FcgammaR) provide important immunoregulation. Targeting
      inhibitory FcgammaRIIb may therefore prolong allograft survival, but its role in
      transplantation has not been addressed. FcgammaRIIb signaling was examined in
      murine models of acute or chronic cardiac allograft rejection by transplanting
      recipients that either lacked FcgammaRIIb expression (FcgammaRIIb(-/-)) or
      overexpressed FcgammaRIIb on B cells (B cell transgenic [BTG]). Acute heart
      allograft rejection occurred at the same tempo in FcgammaRIIb(-/-) C57BL/6 (B6)
      recipients as wild type recipients, with similar IgG alloantibody responses. In
      contrast, chronic rejection of MHC class II-mismatched bm12 cardiac allografts
      was accelerated in FcgammaRIIb(-/-) mice, with development of more severe
      transplant arteriopathy and markedly augmented effector autoantibody production.
      Autoantibody production was inhibited and rejection was delayed in BTG
      recipients. Similarly, whereas MHC class I-mismatched B6.K(d) hearts survived
      indefinitely and remained disease free in B6 mice, much stronger alloantibody
      responses and progressive graft arteriopathy developed in FcgammaRIIb(-/-)
      recipients. Notably, FcgammaRIIb-mediated inhibition of B6.K(d) heart graft
      rejection was abrogated by increasing T cell help through transfer of additional
      H2.K(d)-specific CD4 T cells. Thus, inhibitory FcgammaRIIb signaling regulates
      chronic but not acute rejection, most likely because the supra-optimal helper CD4
      T cell response in acute rejection overcomes FcgammaRIIb-mediated inhibition of
      the effector B cell population. Immunomodulation of FcgammaRIIb in clinical
      transplantation may hold potential for inhibiting progression of transplant
      arteriopathy and prolonging transplant survival.

PMID- 23150719
TI  - Regulation of mitochondrial oxidative metabolism by tumor suppressor FLCN.
AB  - BACKGROUND: Birt-Hogg-Dube (BHD) syndrome is a hereditary hamartoma syndrome that
      predisposes patients to develop hair follicle tumors, lung cysts, and kidney
      cancer. Genetic studies of BHD patients have uncovered the causative gene, FLCN,
      but its function is incompletely understood. METHODS: Mice with conditional
      alleles of FLCN and/or peroxisome proliferator-activated receptor gamma
      coactivator 1-alpha (PPARGC1A), a transcriptional coactivator that regulates
      mitochondrial biogenesis, were crossbred with mice harboring either muscle
      creatine kinase (CKM) -Cre or myogenin (MYOG) -Cre transgenes to knock out FLCN
      and/or PPARGC1A in muscle, or cadherin 16 (CDH16)- Cre transgenes to knock out
      FLCN and/or PPARGC1A in kidney. Real-time polymerase chain reaction,
      immunoblotting, electron microscopy, and metabolic profiling assay were performed
      to evaluate mitochondrial biogenesis and function in muscle. Immunoblotting,
      electron microscopy, and histological analysis were used to investigate
      expression and the pathological role of PPARGC1A in FLCN-deficient kidney. Real
      time polymerase chain reaction, oxygen consumption measurement, and flow
      cytometry were carried out using a FLCN-null kidney cancer cell line. All
      statistical analyses were two-sided. RESULTS: Muscle-targeted FLCN knockout mice
      underwent a pronounced metabolic shift toward oxidative phosphorylation,
      including increased mitochondrial biogenesis (FLCN ( f/f ) vs FLCN ( f/f ) /CKM
      Cre: % mitochondrial area mean = 7.8% vs 17.8%; difference = 10.0%; 95%
      confidence interval = 5.7% to 14.3%; P < .001), and the observed increase in
      mitochondrial biogenesis was PPARGC1A dependent. Reconstitution of FLCN-null
      kidney cancer cells with wild-type FLCN suppressed mitochondrial metabolism and
      PPARGC1A expression. Kidney-targeted PPARGC1A inactivation partially rescued the
      enlarged kidney phenotype and abrogated the hyperplastic cells observed in the
      FLCN-deficient kidney. CONCLUSION: FLCN deficiency and subsequent increased
      PPARGC1A expression result in increased mitochondrial function and oxidative
      metabolism as the source of cellular energy, which may give FLCN-null kidney
      cells a growth advantage and drive hyperplastic transformation.

PMID- 23150720
TI  - Roles played by chemolipiodolization and embolization in chemoembolization for
      hepatocellular carcinoma: single-blind, randomized trial.
AB  - BACKGROUND: The aim of our study was to compare the efficacy and safety of: 1)
      transarterial chemolipiodolization with gelatin sponge embolization vs
      chemolipiodolization without embolization, and 2) chemolipiodolization with
      triple chemotherapeutic agents vs epirubicin alone. METHODS: A single-blind,
      three parallel arm, randomized trial was conducted at three clinical centers with
      patients with biopsy-confirmed unresectable hepatocellular carcinoma. Arm 1
      received triple-drug chemolipiodolization and sponge embolization, whereas Arm 2
      received triple-drug chemolipiodolization only. Patients in arm 3 were treated
      with single-drug chemolipiodolization and sponge embolization. We compared
      overall survival and time to progression. Event-time distributions were estimated
      by the Kaplan-Meier method. All statistical tests were two-sided. RESULTS: From
      July 2007 to November 2009, 365 patients (Arm 1: n = 122; Arm 2: n = 121; Arm 3:
      n = 122) were recruited. The median tumor size was 10.9cm (range = 7-22cm), and
      34.5% had macrovascular invasion. The median survivals and time to progression in
      Arm 1, Arm 2, and Arm 3 were 10.5 and 3.6 months, 10.1 and 3.1 months, and 5.9
      and 3.1 months, respectively. Survival was statistically significantly better in
      Arm 1 than in Arm 3 (P < .001), whereas there was no statistically significant
      difference between Arm 1 and Arm 2 (P = .20). Objective response rates were
      45.9%, 29.7%, and 18.9% for Arm 1, Arm 2, and Arm 3, respectively. CONCLUSIONS:
      Chemolipiodolization played an important role in transarterial chemoembolization,
      and the choice of chemotherapy regimen may largely affect survival outcomes.
      However, the removal of embolization from chemoembolization might not
      statistically significantly decrease survival.

PMID- 23150721
TI  - Thermally sensitive block copolymer particles prepared via aerosol flow reactor
      method: Morphological characterization and behavior in water.
AB  - This work describes properties of thermo-sensitive submicron sized particles
      having the same chemical composition but different morphologies. These particles
      have been prepared with an aerosol technique using dimethylformamide solutions of
      linear polystyrene-block-poly(N-isopropylacrylamide-block-polystyrene, PS-b
      PNIPAM-b-PS. The particles were characterized by cryo-electron microscopy,
      microcalorimetry, and light scattering. Block-copolymers self-assembled within
      the particles forming onion-like, gyroid-like, and spherical morphologies having
      poly(N-isopropylacrylamide) matrix and physically cross-linking polystyrene
      domains. The particles were dispersed in aqueous media and their behavior in
      water was studied both below and above the lower critical solution temperature of
      poly(N-isopropylacrylamide). We found out that the particles with spherical and
      gyroid-like morphologies swell considerably in water at 20  degrees C, whereas at
      40  degrees C the particles resemble more of those studied without water
      treatment. Light scattering experiments showed that the particles gradually
      aggregate and precipitate with time at 40  degrees C. Microcalorimetric studies
      revealed for all three studied morphologies that PNIPAM undergoes a two-step
      transition due to the different hydration levels of PNIPAM inside and outside the
      particles. Thicknesses of the PS and PNIPAM layers within the onion-like
      particles were analyzed using the TEM micrographs by fitting a model of electron
      density to the integrated electron intensity data. The surface layer of the
      particles was found out to be PNIPAM, which was supported by light scattering and
      microcalorimetry. It was also found out from the TEM micrograph analysis that the
      width of the outmost PS layer is considerably thinner than the one in the dry
      state prior to immersion in water, and a degradation scheme is proposed to
      explain these results.

PMID- 23150723
TI  - Five-year follow-up of patients with early stage breast cancer after a randomized
      study comparing additional treatment with viscum album (L.) extract to
      chemotherapy alone.
AB  - Additional therapy with extracts of Viscum album [L.] (VaL) increases the quality
      of life of patients suffering from early stage breast cancer during chemotherapy.
      In the current study patients received chemotherapy, consisting of six cycles of
      cyclophosphamide, anthracycline, and 5-Fluoro-Uracil (CAF). Two groups also
      received one of two VaL extracts differing in their preparation as subcutaneous
      injection three times per week. A control group received CAF with no additional
      therapy. Six of 28 patients in one of the VaL groups and eight of 29 patients in
      the control group developed relapse or metastasis within 5 years. Subgroup
      analysis for hormone- and radiotherapy also showed no difference between groups.
      Additional VaL therapy during chemotherapy of early stage breast cancer patients
      appears not to influence the frequency of relapse or metastasis within 5 years.

PMID- 23150722
TI  - Vitreous analysis in the management of uveitis.
AB  - A correct diagnosis of uveitis is often challenging, given the wide range of
      possible underlying conditions and the lack of typical phenotypes. Management
      decisions may be difficult in view of the risk of visual loss with either
      inappropriate or delayed therapy. Analysis of the vitreous may therefore be used
      to provide the clinician with valuable information. In this paper, we describe
      the main clinical situations in which vitreous sampling is indicated and provide
      some guidance to clinicians for tailoring their requests. These situations
      include suspected intraocular infection and suspected intraocular malignancy. We
      describe the principal tests carried out on vitreous samples, including cultures,
      polymerase chain reaction-based testing, and cytokine analysis. Limitations of
      the tests used are likely to become less as more advanced testing methods are
      introduced. The importance of selecting the appropriate investigations to support
      a clinical suspicion is emphasised, as is the interpretation of test results
      within a clinical context.

PMID- 23150724
TI  - Fate of dietary tryptophan in young Japanese women.
AB  - The purpose of this study was to determine, using the high-performance liquid
      chromatographic methods recently modified by us, the fate of dietary tryptophan
      in 17 healthy female Japanese adults who ate self-selected food. The experimental
      period was 22 days. The habitual intake of tryptophan was 3328.4 MUmol/day. 24
      hour urine samples were collected at the beginning of the experiment and then
      once per week. Blood was collected at the beginning and end of the experiment.
      Levels of tryptophan and its metabolites were measured in blood and urine.
      Tryptophan, nicotinamide and 2-oxoadipic acid were the major compounds of the
      blood. The urinary excretion amounts of tryptophan, 5-hydroxyindole-3-acetic
      acid, kynurenine, anthranilic acid, kynurenic acid, 3-hydroxykynurenine,
      xanthurenic acid, 3-hydroxyanthranilic acid and quinolinic acid were about 40,
      20, 4, 1, 10, 4, 3, 5 and 20 MUmol/day, respectively.

PMID- 23150725
TI  - In Vitro and In Vivo Characterizations of Chiglitazar, a Newly Identified PPAR
      Pan-Agonist.
AB  - Solid rationales are still present for the identification of synthetic ligands to
      simultaneously target multiple PPAR subtypes for the treatment of T2DM. The
      purpose of this study was to characterize the in vitro and in vivo differential
      effects of chiglitazar, a non-TZD type of PPAR pan-agonist currently in phase III
      clinic development in China, from PPARgamma-selective agonist like rosiglitazone.
      Chiglitazar showed transactivating activity in each PPARalpha, gamma, and delta
      subtype and upregulated the expression of PPARalpha and/or PPARdelta downstream
      genes involved in the key processes of lipid metabolism and thermogenesis.
      Comparable blood glucose lowering effect was observed between chiglitazar and
      rosiglitazone, but chiglitazar did not significantly increase the body weight in
      KKAy and fat pad weight in db/db mice. Chiglitazar had high distribution in
      liver, pancreas, and skeleton muscles but was less present in kidney, heart, and
      adipose in rats. Heart weight increase was not observed in rats treated with
      chiglitazar for 6 months at a dose as high as 45 mg kg(-1). The in vitro and in
      vivo differential features of chiglitazar are informative and encouraging for the
      further development of this synthetic ligand for the potential use in T2DM.

PMID- 23150727
TI  - Sex steroids and bone health status in men.
AB  - Male osteoporosis is a health problem which deserves more attention as nearly 30%
      of osteoporotic fractures happen in men aged 50 years and above. Although men do
      not experience an accelerated bone loss phase and testosterone deficiency is not
      a universal characteristic for aged men, osteoporosis due to age-related
      testosterone deficiency does have a negative impact on bone health status of men.
      Observations from epidemiological studies indicate that elderly men with higher
      testosterone can preserve their BMD better and thus are less prone to fracture.
      Observations on men with estrogen resistance or aromatase deficiency indicate
      that estrogen is equally important in the maintenance of bone health status. This
      had been validated in several epidemiological studies which found that the
      relationships between estrogen and bone health indices are significant and
      sometimes stronger than testosterone. Studies on the relationship between
      quantitative ultrasound and bone remodeling markers suggest that testosterone and
      estrogen may have differential effects on bone, but further evidence was needed.
      In conclusion, both testosterone and estrogen are important in the maintenance of
      bone health in men.

PMID- 23150726
TI  - Regulation of Genes Involved in Carnitine Homeostasis by PPARalpha across
      Different Species (Rat, Mouse, Pig, Cattle, Chicken, and Human).
AB  - Recent studies in rodents convincingly demonstrated that PPARalpha is a key
      regulator of genes involved in carnitine homeostasis, which serves as a
      reasonable explanation for the phenomenon that energy deprivation and fibrate
      treatment, both of which cause activation of hepatic PPARalpha, causes a strong
      increase of hepatic carnitine concentration in rats. The present paper aimed to
      comprehensively analyse available data from genetic and animal studies with mice,
      rats, pigs, cows, and laying hens and from human studies in order to compare the
      regulation of genes involved in carnitine homeostasis by PPARalpha across
      different species. Overall, our comparative analysis indicates that the role of
      PPARalpha as a regulator of carnitine homeostasis is well conserved across
      different species. However, despite demonstrating a well-conserved role of
      PPARalpha as a key regulator of carnitine homeostasis in general, our
      comprehensive analysis shows that this assumption particularly applies to the
      regulation by PPARalpha of carnitine uptake which is obviously highly conserved
      across species, whereas regulation by PPARalpha of carnitine biosynthesis appears
      less well conserved across species.

PMID- 23150728
TI  - Palm tocotrienol supplementation enhanced bone formation in oestrogen-deficient
      rats.
AB  - Postmenopausal osteoporosis is the commonest cause of osteoporosis. It is
      associated with increased free radical activity induced by the oestrogen
      deficient state. Therefore, supplementation with palm-oil-derived tocotrienols, a
      potent antioxidant, should be able to prevent this bone loss. Our earlier studies
      have shown that tocotrienol was able to prevent and even reverse osteoporosis due
      to various factors, including oestrogen deficiency. In this study we compared the
      effects of supplementation with palm tocotrienol mixture or calcium on bone
      biomarkers and bone formation rate in ovariectomised (oestrogen-deficient) female
      rats. Our results showed that palm tocotrienols significantly increased bone
      formation in oestrogen-deficient rats, seen by increased double-labeled surface
      (dLS/Bs), reduced single-labeled surface (sLS/BS), increased mineralizing surface
      (MS/BS), increased mineral apposition rate (MAR), and an overall increase in bone
      formation rate (BFR/BS). These effects were not seen in the group supplemented
      with calcium. However, no significant changes were seen in the serum levels of
      the bone biomarkers, osteocalcin, and cross-linked C-telopeptide of type I
      collagen, CTX. In conclusion, palm tocotrienol is more effective than calcium in
      preventing oestrogen-deficient bone loss. Further studies are needed to determine
      the potential of tocotrienol as an antiosteoporotic agent.

PMID- 23150729
TI  - Relationship of morning cortisol to circadian phase and rising time in young
      adults with delayed sleep times.
AB  - The present study was aimed at further elucidating the relationship between
      circadian phase, rising time, and the morning cortisol awakening response (CAR).
      The results presented here are a secondary analysis of experimental data obtained
      from a study of advanced sleep-wake schedules and light exposures on circadian
      phase advances measured by dim-light melatonin onset (DLMO). The present results
      demonstrate that morning CAR is strongly related to rising time and more weakly
      related to DLMO phase.

PMID- 23150730
TI  - Patterns of cancer genetic testing: a randomized survey of Oregon clinicians.
AB  - Introduction. Appropriate use of genetic tests for population-based cancer
      screening, diagnosis of inherited cancers, and guidance of cancer treatment can
      improve health outcomes. We investigated clinicians' use and knowledge of eight
      breast, ovarian, and colorectal cancer genetic tests. Methods. We conducted a
      randomized survey of 2,191 Oregon providers, asking about their experience with
      fecal DNA, OncoVue, BRCA, MMR, CYP2D6, tumor gene expression profiling, UGT1A1,
      and KRAS. Results. Clinicians reported low confidence in their knowledge of
      medical genetics; most confident were OB-GYNs and specialists. Clinicians were
      more likely to have ordered/recommended BRCA and MMR than the other tests, and OB
      GYNs were twice as likely to have ordered/recommended BRCA testing than primary
      care providers. Less than 10% of providers ordered/recommended OncoVue, fecal
      DNA, CYP2D6, or UGT1A1; less than 30% ordered/recommended tumor gene expression
      profiles or KRAS. The most common reason for not ordering/recommending these
      tests was lack of familiarity. Conclusions. Use of appropriate, evidence-based
      testing can help reduce incidence and mortality of certain cancers, but these
      tests need to be better integrated into clinical practice. Continued evaluation
      of emerging technologies, dissemination of findings, and an increase in provider
      confidence and knowledge are necessary to achieve this end.

PMID- 23150731
TI  - Barriers and facilitators for utilization of genetic counseling and risk
      assessment services in young female breast cancer survivors.
AB  - Introduction. Women diagnosed with breast cancer at a young age are more likely
      to carry a cancer predisposing genetic mutation. Per the current NCCN
      recommendations, women diagnosed under age 50 should be referred to cancer
      genetic counseling for further risk evaluation. This study seeks to assess
      patient-reported barriers and facilitators to receiving genetic counseling and
      risk assessment among a community-based population of young breast cancer
      survivors (YBCS). Methods. Through the Michigan Cancer Surveillance Program, a
      state-based cancer registry, 488 women diagnosed with breast cancer before age 50
      in 2006-2007 were identified. They received a mail survey regarding family
      history and facilitators and barriers to receiving genetic counseling and risk
      assessment. Results. Responses were received from 289 women (59.2%). One hundred
      twenty-two (42.2%) reported having received cancer genetic counseling. The most
      frequent reason identified for receiving services was to benefit their family's
      future. The top reasons for not attending were "no one recommended it" and
      "medical insurance coverage issues." Discussion. This study is the first
      published report using a state cancer registry to determine facilitators and
      barriers to receiving genetic counseling and risk assessment among YBCS. These
      findings demonstrate the need for additional awareness and education about
      appropriate indications for genetic services.

PMID- 23150732
TI  - Sciatic hernia mimicking perianal abscess in a cirrhotic patient.
AB  - Abdominal hernias are very frequent in cirrhotic patients with ascites. The
      hernias usually present as umbilical, inguinal, incisional, or femoral. However,
      these patients can also develop uncommon hernias such as pelvic hernias because
      of pelvic floor weakness and high abdominal pressure due to ascites. We present
      the first case of a cirrhotic patient with ascites that developed a giant sciatic
      hernia mimicking a perianal abscess.

PMID- 23150733
TI  - Metastasis of dermatofibrosarcoma from the abdominal wall to the thyroid gland:
      case report.
AB  - Metastases in the thyroid gland are very rare. Even the rarer are sarcoma
      metastases. A 52-year-old woman was referred to our department for evaluation of
      a nodule in the right lobe of the thyroid gland. She had a history dermatosarcoma
      of the abdominal wall with known metastasis in the lung. Clinically she had neck
      pain and worsened swallowing. Objective assessment (ultrasound, computed
      tomography, and magnetic resonance) indicated a voluminous right lobe nodule with
      mechanical syndrome, and a fine-needle aspiration biopsy revealed a very
      suspicious malignant finding. After surgery, the diagnosis was metastasis of
      dermatofibrosarcoma protuberans. Subsequent treatment was radio- and
      chemotherapy.

PMID- 23150734
TI  - Giant pelvic retroperitoneal epidermoid cyst: a rare case report.
AB  - Epidermoid cyst is a frequent benign cutaneous tumor. The pelvic localization
      does not occur very often. The literature that taps into such cases is very
      limited in scope. Here is a report of a 27-year-old woman with a giant pelvic
      retroperitoneal epidermoid cyst. The use of ultrasound exploration and computed
      tomography has indicated ovarian origins. The surgery also revealed a
      retroperitoneal epidermoid cyst, uterus and ovaries were all intact. The
      evacuation of a cyst was found to contain lamellas of keratin. Histology
      permitted us to confirm the diagnosis. The patient was faring well after two
      years of followup.

PMID- 23150735
TI  - Effects of intravenous administration of human umbilical cord blood stem cells in
      3-acetylpyridine-lesioned rats.
AB  - Cerebellar ataxias include a heterogeneous group of infrequent diseases
      characterized by lack of motor coordination caused by disturbances in the
      cerebellum and its associated circuits. Current therapies are based on the use of
      drugs that correct some of the molecular processes involved in their
      pathogenesis. Although these treatments yielded promising results, there is not
      yet an effective therapy for these diseases. Cell replacement strategies using
      human umbilical cord blood mononuclear cells (HuUCBMCs) have emerged as a
      promising approach for restoration of function in neurodegenerative diseases. The
      aim of this work was to investigate the potential therapeutic activity of
      HuUCBMCs in the 3-acetylpyridine (3-AP) rat model of cerebellar ataxia.
      Intravenous administered HuUCBMCs reached the cerebellum and brain stem of 3-AP
      ataxic rats. Grafted cells reduced 3-AP-induced neuronal loss promoted the
      activation of microglia in the brain stem, and prevented the overexpression of
      GFAP elicited by 3-AP in the cerebellum. In addition, HuUCBMCs upregulated the
      expression of proteins that are critical for cell survival, such as phospho-Akt
      and Bcl-2, in the cerebellum and brain stem of 3-AP ataxic rats. As all these
      effects were accompanied by a temporal but significant improvement in motor
      coordination, HuUCBMCs grafts can be considered as an effective cell replacement
      therapy for cerebellar disorders.

PMID- 23150736
TI  - Neuronal modulation of airway and vascular tone and their influence on
      nonspecific airways responsiveness in asthma.
AB  - The autonomic nervous system provides both cholinergic and noncholinergic neural
      inputs to end organs within the airways, which includes the airway and vascular
      smooth muscle. Heightened responsiveness of the airways to bronchoconstrictive
      agents is a hallmark feature of reactive airways diseases. The mechanisms
      underpinning airways hyperreactivity still largely remain unresolved. In this
      paper we summarize the substantial body of evidence that implicates dysfunction
      of the autonomic nerves that innervate smooth muscle in the airways and
      associated vasculature as a prominent cause of airways hyperresponsiveness in
      asthma.

PMID- 23150737
TI  - The contribution of allergen-specific IgG to the development of th2-mediated
      airway inflammation.
AB  - In both human asthmatics and animal models of allergy, allergen-specific IgG can
      contribute to Th2-mediated allergic inflammation. Mouse models have elucidated an
      important role for IgG and Fc-gamma receptor (FcgammaR) signaling on antigen
      presenting cells (APC) for the induction of airway inflammation. These studies
      suggest a positive feedback loop between IgG produced by the adaptive B cell
      response and FcgammaR signaling on innate immune cells. Studies of IgG and
      FcgammaRs in humans with asthma or allergic lung disease have been more
      controversial. Some reports have identified associations between allergen
      specific IgG and severity of allergic responses, while other studies have found
      associations of IgG subclass IgG4 with allergic tolerance. In this paper, we
      review the literature to help define the nature of IgG and FcgammaR signaling on
      innate immune cells and how it contributes to the development of allergic immune
      responses.

PMID- 23150738
TI  - Nutritional aspects in diagnosis and management of food hypersensitivity-the
      dietitians role.
AB  - Many common foods including cow's milk, hen's egg, soya, peanut, tree nuts, fish,
      shellfish, and wheat may cause food allergies. The prevalence of these immune
      mediated adverse reactions to foods ranges from 0.5% to 9% in different
      populations. In simple terms, the cornerstone of managing food allergy is to
      avoid consumption of foods causing symptoms and to replace them with
      nutritionally equivalent foods. If poorly managed, food allergy impairs quality
      of life more than necessary, affects normal growth in children, and causes an
      additional economic burden to society. Delay in diagnosis may be a further
      incremental factor. Thus, an increased awareness of the appropriate procedures
      for both diagnosis and management is of importance. This paper sets out to
      present principles for taking an allergy-focused diet history as part of the
      diagnostic work-up of food allergy. A short overview of guidelines and principles
      for dietary management of food allergy is discussed focusing on the nutritional
      management of food allergies and the particular role of the dietitian in this
      process.

PMID- 23150739
TI  - In Vivo Study on the Pharmacological Interactions between a Chinese Herbal
      Formula ELP and Antiresorptive Drugs to Counteract Osteoporosis.
AB  - Antiresorptive drugs, alendronate and raloxifene, are effective in lowering bone
      mineral density (BMD) loss in postmenopausal women. However, long-term treatment
      may be associated with serious side effects. Our research group has recently
      discovered that a Chinese herbal formula, ELP, could significantly reduce BMD
      loss in animal and human studies. Therefore, the present study aimed to
      investigate the potential synergistic bone-protective effects of different herb
      drug combinations using ovariectomized rats. To assess the efficacy of different
      combinations, the total BMD was monitored biweekly in the 8-week course of daily
      oral treatment. Bone microarchitecture, bone strength, and deoxypyridinoline
      level were also determined after 8 weeks. From our results, coadministration of
      ELP and raloxifene increased the total tibial BMD by 5.26% (2.5 mg/kg/day of
      raloxifene; P = 0.014) and 5.94% (0.25 mg/kg/day of raloxifene; P = 0.026) when
      compared with the respective dosage groups with raloxifene alone. Similar
      synergistic effects were also observed in BMD increase at distal femur (0.25
      mg/kg/day; P = 0.001) and reduction in urinary deoxypyridinoline crosslink
      excretion (2.5 and 0.25 mg/kg/day; both P = 0.02). However, such interactions
      could not be observed in all alendronate-treated groups. Our data provide first
      evidence that ELP could synergistically enhance the therapeutic effects of
      raloxifene, so that the clinical dosage of raloxifene could be reduced.

PMID- 23150740
TI  - Using the K-nearest neighbor algorithm for the classification of lymph node
      metastasis in gastric cancer.
AB  - Accurate tumor, node, and metastasis (TNM) staging, especially N staging in
      gastric cancer or the metastasis on lymph node diagnosis, is a popular issue in
      clinical medical image analysis in which gemstone spectral imaging (GSI) can
      provide more information to doctors than conventional computed tomography (CT)
      does. In this paper, we apply machine learning methods on the GSI analysis of
      lymph node metastasis in gastric cancer. First, we use some feature selection or
      metric learning methods to reduce data dimension and feature space. We then
      employ the K-nearest neighbor classifier to distinguish lymph node metastasis
      from nonlymph node metastasis. The experiment involved 38 lymph node samples in
      gastric cancer, showing an overall accuracy of 96.33%. Compared with that of
      traditional diagnostic methods, such as helical CT (sensitivity 75.2% and
      specificity 41.8%) and multidetector computed tomography (82.09%), the diagnostic
      accuracy of lymph node metastasis is high. GSI-CT can then be the optimal choice
      for the preoperative diagnosis of patients with gastric cancer in the N staging.

PMID- 23150741
TI  - Environment-Responsive Polymers for Coating of Pharmaceutical Nanocarriers(,).
AB  - Polyethylene glycol derivatives, such as block copolymers of polyethylene glycol
      and diacyllipids (for example, phosphatidylethanolamine) are widely used for
      surface modification of various pharmaceutical carriers in order to impart them
      longevity in the body. To make polyethylene glycol detachable from the surface of
      pharmaceutical carrier and facilitate the interaction of the carrier with target
      cells when in pathological zone, we have prepared a set of polyethylene glycol
      phosphatidylethanolamine block copolymers with the pH sensitive hydrazone bond
      between polyethylene glycol and phosphatidylethanolamine, which destabilizes at
      lowered pH values typical for tumors and inflammation zones. We have demonstrated
      that the stability of the hydrazone bond at normal physiological pH (7.4) as well
      as the rate of its hydrolysis at pH 6 and below strongly depend on the type of
      substitutions at this bond. Using aliphatic and aromatic aldehydes and ketones,
      polyethylene glycol-phosphatidylethanolamine block copolymers were prepared with
      different stabilities and degradation rates, which can be useful in constructing
      stimuli-sensitive pharmaceutical carriers.

PMID- 23150742
TI  - Myocardial chemokine expression and intensity of myocarditis in Chagas
      cardiomyopathy are controlled by polymorphisms in CXCL9 and CXCL10.
AB  - BACKGROUND: Chronic Chagas cardiomyopathy (CCC), a life-threatening inflammatory
      dilated cardiomyopathy, affects 30% of the approximately 8 million patients
      infected by Trypanosoma cruzi. Even though the Th1 T cell-rich myocarditis plays
      a pivotal role in CCC pathogenesis, little is known about the factors controlling
      inflammatory cell migration to CCC myocardium. METHODS AND RESULTS: Using
      confocal immunofluorescence and quantitative PCR, we studied cell surface
      staining and gene expression of the CXCR3, CCR4, CCR5, CCR7, CCR8 receptors and
      their chemokine ligands in myocardial samples from end-stage CCC patients. CCR5+,
      CXCR3+, CCR4+, CCL5+ and CXCL9+ mononuclear cells were observed in CCC
      myocardium. mRNA expression of the chemokines CCL5, CXCL9, CXCL10, CCL17, CCL19
      and their receptors was upregulated in CCC myocardium. CXCL9 mRNA expression
      directly correlated with the intensity of myocarditis, as well as with mRNA
      expression of CXCR3, CCR4, CCR5, CCR7, CCR8 and their ligands. We also analyzed
      single-nucleotide polymorphisms for genes encoding the most highly expressed
      chemokines and receptors in a cohort of Chagas disease patients. CCC patients
      with ventricular dysfunction displayed reduced genotypic frequencies of CXCL9
      rs10336 CC, CXCL10 rs3921 GG, and increased CCR5 rs1799988CC as compared to those
      without dysfunction. Significantly, myocardial samples from CCC patients carrying
      the CXCL9/CXCL10 genotypes associated to a lower risk displayed a 2-6 fold
      reduction in mRNA expression of CXCL9, CXCL10, and other chemokines and
      receptors, along with reduced intensity of myocarditis, as compared to those with
      other CXCL9/CXCL10 genotypes. CONCLUSIONS: Results may indicate that genotypes
      associated to reduced risk in closely linked CXCL9 and CXCL10 genes may modulate
      local expression of the chemokines themselves, and simultaneously affect
      myocardial expression of other key chemokines as well as intensity of
      myocarditis. Taken together our results may suggest that CXCL9 and CXCL10 are
      master regulators of myocardial inflammatory cell migration, perhaps affecting
      clinical progression to the life-threatening form of CCC.

PMID- 23150743
TI  - Structural and binding properties of two paralogous fatty acid binding proteins
      of Taenia solium metacestode.
AB  - BACKGROUND: Fatty acid (FA) binding proteins (FABPs) of helminths are implicated
      in acquisition and utilization of host-derived hydrophobic substances, as well as
      in signaling and cellular interactions. We previously demonstrated that secretory
      hydrophobic ligand binding proteins (HLBPs) of Taenia solium metacestode (TsM), a
      causative agent of neurocysticercosis (NC), shuttle FAs in the surrounding host
      tissues and inwardly transport the FAs across the parasite syncytial membrane.
      However, the protein molecules responsible for the intracellular trafficking and
      assimilation of FAs have remained elusive. METHODOLOGY/PRINCIPAL FINDINGS: We
      isolated two novel TsMFABP genes (TsMFABP1 and TsMFABP2), which encoded 133- and
      136-amino acid polypeptides with predicted molecular masses of 14.3 and 14.8 kDa,
      respectively. They shared 45% sequence identity with each other and 15-95% with
      other related-members. Homology modeling demonstrated a characteristic beta
      barrel composed of 10 anti-parallel beta-strands and two alpha-helices. TsMFABP2
      harbored two additional loops between beta-strands two and three, and beta
      strands six and seven, respectively. TsMFABP1 was secreted into cyst fluid and
      surrounding environments, whereas TsMFABP2 was intracellularly confined.
      Partially purified native proteins migrated to 15 kDa with different isoelectric
      points of 9.2 (TsMFABP1) and 8.4 (TsMFABP2). Both native and recombinant proteins
      bound to 11-([5-dimethylaminonaphthalene-1-sulfonyl]amino)undecannoic acid,
      dansyl-DL-alpha-amino-caprylic acid, cis-parinaric acid and retinol, which were
      competitively inhibited by oleic acid. TsMFABP1 exhibited high affinity toward FA
      analogs. TsMFABPs showed weak binding activity to retinol, but TsMFABP2 showed
      relatively high affinity. Isolation of two distinct genes from an individual
      genome strongly suggested their paralogous nature. Abundant expression of
      TsMFABP1 and TsMFABP2 in the canal region of worm matched well with the
      histological distributions of lipids and retinol. CONCLUSIONS/SIGNIFICANCE: The
      divergent biochemical properties, physiological roles and cellular distributions
      of the TsMFABPs might be one of the critical mechanisms compensating for
      inadequate de novo FA synthesis. These proteins might exert harmonized or
      independent roles on lipid assimilation and intracellular signaling. The
      specialized distribution of retinol in the canal region further implies that
      cells in this region might differentiate into diverse cell types during
      metamorphosis into an adult worm. Identification of bioactive systems pertinent
      to parasitic homeostasis may provide a valuable target for function-related drug
      design.

PMID- 23150744
TI  - Cytokine responses to novel antigens in an Indian population living in an area
      endemic for visceral leishmaniasis.
AB  - BACKGROUND: There are no effective vaccines for visceral leishmaniasis (VL), a
      neglected parasitic disease second only to malaria in global mortality. We
      previously identified 14 protective candidates in a screen of 100 Leishmania
      antigens as DNA vaccines in mice. Here we employ whole blood assays to evaluate
      human cytokine responses to 11 of these antigens, in comparison to known defined
      and crude antigen preparations. METHODS: Whole blood assays were employed to
      measure IFN-gamma, TNF-alpha and IL-10 responses to peptide pools of the novel
      antigens R71, Q51, L37, N52, L302.06, J89, M18, J41, M22, M63, M57, as well as to
      recombinant proteins of tryparedoxin peroxidase (TRYP), Leishmania homolog of the
      receptor for activated C kinase (LACK) and to crude soluble Leishmania antigen
      (SLA), in Indian patients with active (n = 8) or cured (n = 16) VL, and in
      modified Quantiferon positive (EHC(+ve), n = 20) or modified Quantiferon negative
      (EHC(-ve), n = 9) endemic healthy controls (EHC). RESULTS: Active VL, cured VL
      and EHC(+ve) groups showed elevated SLA-specific IFN-gamma, but only active VL
      patients produced IL-10 and EHC(+ve) did not make TNF-alpha. IFN-gamma to IL-10
      and TNF-alpha to IL-10 ratios in response to TRYP and LACK antigens were higher
      in cured VL and EHC(+ve) exposed individuals compared to active VL. Five of the
      eleven novel candidates (R71, L37, N52, J41, and M22) elicited IFN-gamma and TNF
      alpha, but not IL-10, responses in cured VL (55-87.5% responders) and EHC(+ve)
      (40-65% responders) subjects. CONCLUSIONS: Our results are consistent with an
      important balance between pro-inflammatory IFNgamma and TNFgamma cytokine
      responses and anti-inflammatory IL-10 in determining outcome of VL in India, as
      highlighted by response to both crude and defined protein antigens. Importantly,
      cured VL patients and endemic Quantiferon positive individuals recognise 5 novel
      vaccine candidate antigens, confirming our recent data for L. chagasi in Brazil,
      and their potential as cross-species vaccine candidates.

PMID- 23150745
TI  - Comparative evaluation of silver-containing antimicrobial dressings on in vitro
      and in vivo processes of wound healing.
AB  - OBJECTIVES: To compare the in vitro and in vivo effects of silver products on
      wound healing. METHODS: Eight silver products were compared to determine:
      fibroblast function using fibroblast-populated collagen lattices (FPCLs),
      fibroblast viability using the Trypan Blue exclusion test, and fibroblast
      mitochondrial activity using the MTT [yellow tetrazolium salt; 3-(4,5
      Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay. In vivo effects of
      9 silver products were evaluated utilizing a rat model of contaminated wounds.
      Serial quantitative bacteriology was performed on tissue biopsies over a 10-day
      period and serial wound areas were obtained over 12 days. RESULTS: Fibroblast
      cytotoxicity occurred for all of the silver products evaluated. Remaining viable
      fibroblasts were insufficient to allow FPCL contraction. Mitochondrial activity
      of the fibroblasts allowed a separation of the various silver compounds. Actisorb
      Silver and Silvercel had the greatest viable fibroblast activity, but less than
      the control. Despite in vitro cytotoxicity, all of the silver products except
      Contreet Foam and Acticoat Moisture Control accelerated wound healing.
      CONCLUSIONS: Silver-containing dressings appeared to benefit healing of the
      wounds. Just as in vitro bacterial analyses do not fully predict the effect of an
      antimicrobial in the in vivo setting, in vitro cytotoxicity tests do not fully
      predict the effect of an agent on wound healing trajectories. Because of the
      varied antimicrobial and wound healing responses among products, a careful
      consideration of the particular effects of individual silver-containing dressings
      or drugs is warranted.

PMID- 23150746
TI  - Elephantiasis nostras verrucosa.

PMID- 23150747
TI  - A Rapid Response to Matrix Therapy With RGTA in Severe Epidermolysis Bullosa.

PMID- 23150748
TI  - Reversible oxidation of myometrial voltage-gated potassium channels with hydrogen
      peroxide.
AB  - The uteri, spontaneously active or Ca(2+) (6 mM) induced, were allowed to
      equilibrate, and to inhibit voltage-gated potassium (K(V)) channels 1 mM 4-amino
      pyridine (4-AP) was applied for 15 min before adding H(2)O(2). H(2)O(2) was added
      cumulatively: 2 MUM, 20 MUM, 200 MUM, 400 MUM, and 3 mM. Average time for
      H(2)O(2) concentrations (2, 20, 200, and 400) MUM to reach its full effect was 15
      min. H(2)O(2) 3 mM had a prolonged effect and therefore was left to act for 30
      min. Two-way ANOVA showed significant differences in time dependency between
      spontaneous and Ca(2+)-induced rat uteri after applying 3 mM H(2)O(2) (type of
      contraction, P = 0.0280), but not 400 MUM H(2)O(2) (P = 0.9271). Our results
      indicate that H(2)O(2) oxidises channel intracellular thiol groups and activates
      the channel, inducing relaxation. Cell antioxidative defence system quickly
      activates glutathione peroxidase (GSHPx) defence mechanism but not catalase (CAT)
      defence mechanism. Intracellular redox mechanisms repair the oxidised sites and
      again establish deactivation of K(V) channels, recuperating contractility. In
      conclusion, our results demonstrate that K(V) channels can be altered in a time
      dependent manner by reversible redox-dependent intracellular alterations.

PMID- 23150751
TI  - Monographs editor.

PMID- 23150750
TI  - Cocoa polyphenols and their potential benefits for human health.
AB  - This paper compiles the beneficial effects of cocoa polyphenols on human health,
      especially with regard to cardiovascular and inflammatory diseases, metabolic
      disorders, and cancer prevention. Their antioxidant properties may be responsible
      for many of their pharmacological effects, including the inhibition of lipid
      peroxidation and the protection of LDL-cholesterol against oxidation, and
      increase resistance to oxidative stress. The phenolics from cocoa also modify the
      glycemic response and the lipid profile, decreasing platelet function and
      inflammation along with diastolic and systolic arterial pressures, which, taken
      together, may reduce the risk of cardiovascular mortality. Cocoa polyphenols can
      also modulate intestinal inflammation through the reduction of neutrophil
      infiltration and expression of different transcription factors, which leads to
      decreases in the production of proinflammatory enzymes and cytokines. The
      phenolics from cocoa may thus protect against diseases in which oxidative stress
      is implicated as a causal or contributing factor, such as cancer. They also have
      antiproliferative, antimutagenic, and chemoprotective effects, in addition to
      their anticariogenic effects.

PMID- 23150749
TI  - Therapeutic targeting of redox signaling in myofibroblast differentiation and age
      related fibrotic disease.
AB  - Myofibroblast activation plays a central role during normal wound healing.
      Whereas insufficient myofibroblast activation impairs wound healing, excessive
      myofibroblast activation promotes fibrosis in diverse tissues (including benign
      prostatic hyperplasia, BPH) leading to organ dysfunction and also promotes a
      stromal response that supports tumor progression. The incidence of impaired wound
      healing, tissue fibrosis, BPH, and certain cancers strongly increases with age.
      This paper summarizes findings from in vitro fibroblast-to-myofibroblast
      differentiation systems that serve as cellular models to study fibrogenesis of
      diverse tissues. Supported by substantial in vivo data, a large body of evidence
      indicates that myofibroblast differentiation induced by the profibrotic cytokine
      transforming growth factor beta is driven by a prooxidant shift in redox
      homeostasis due to elevated production of NADPH oxidase 4 (NOX4)-derived hydrogen
      peroxide and supported by concomitant decreases in nitric oxide/cGMP signaling
      and reactive oxygen species (ROS) scavenging enzymes. Fibroblast-to-myofibroblast
      differentiation can be inhibited and reversed by restoring redox homeostasis
      using antioxidants or NOX4 inactivation as well as enhancing nitric oxide/cGMP
      signaling via activation of soluble guanylyl cyclases or inhibition of
      phosphodiesterases. Current evidence indicates the therapeutic potential of
      targeting the prooxidant shift in redox homeostasis for the treatment of age
      related diseases associated with myofibroblast dysregulation.

PMID- 23150752
TI  - Mdm2 and tumorigenesis: evolving theories and unsolved mysteries.
AB  - Since the discovery of Mdm2, the contribution of this RING E3 ubiquitin ligase to
      the pathobiology of cancer has focused almost exclusively on its role as a
      negative regulator of the p53 tumor suppressor. Under normal conditions, Mdm2
      promotes the ubiquitin- and proteasome-dependent degradation of p53. Levels of
      p53 are thus kept sufficiently low to allow for cell survival and cell cycle
      progression. In the context of such insults as DNA damage or ribosomal stress,
      however, the Mdm2-p53 interaction is disrupted and p53 is stabilized. The myriad
      intracellular outcomes of p53 activation together comprise a robust program of
      tumor suppression that is short-circuited in cancer. Over half of all human
      malignancies are known to have lost p53 expression or sustained p53 mutation,
      whereas many of the remaining tumors harbor other alterations in key mediators of
      p53 activity that include overexpression of Mdm2. Therapies targeting the
      interaction between Mdm2 and p53 represent a possible means of pharmacologically
      reactivating the p53 pathway in this latter setting. The degree of overlap across
      the biological consequences of either p53 loss or Mdm2 overexpression, however,
      has not been thoroughly explored. Indeed, a body of evidence for several p53
      independent functions of Mdm2 suggests that disrupting the Mdm2-p53 interaction
      may fail to address the full spectrum of oncogenic effects specific to tumors
      that overexpress Mdm2.

PMID- 23150753
TI  - The Regulation of Multiple p53 Stress Responses is Mediated through MDM2.
AB  - The MDM2 oncogene is a key negative regulator of the p53 tumor suppressor
      protein. MDM2 and p53 form an autoregulatory feedback loop to tightly control the
      proper cellular responses to various stress signals in order to prevent mutations
      and tumor formation. The levels and function of the MDM2 protein, an E3 ubiquitin
      ligase, are regulated by a wide variety of extracellular and intracellular stress
      signals through distinct signaling pathways and mechanisms. These signals
      regulate the E3 ubiquitin ligase activity of MDM2, the ability of MDM2 to
      interact with p53 and a number of other proteins, and the cellular localization
      of MDM2, which in turn impact significantly upon p53 function. This review
      provides an overview of the regulation of MDM2 activities by the signals and
      factors that regulate the MDM2 protein, including genotoxic stress signals,
      oncogenic activation, cell cycle transition, ribosomal stress, chronic stress,
      neurohormones, and microRNAs. Disruption of the proper regulation of the MDM2-p53
      negative feedback loop impacts significantly upon the frequency of tumorigenesis
      in a host. A better understanding of the complex regulation of MDM2 and its
      impact upon p53 function in cells under different conditions will help to develop
      novel and more effective strategies for cancer therapy and prevention.

PMID- 23150754
TI  - Using Mouse Models to Explore MDM-p53 Signaling in Development, Cell Growth, and
      Tumorigenesis.
AB  - The p53 transcription factor regulates the expression of numerous genes whose
      products affect cell proliferation, senescence, cellular metabolism, apoptosis,
      and DNA repair. These p53-mediated effects can inhibit the growth of stressed or
      mutated cells and suppress tumorigenesis in the organism. However, the various
      growth-inhibitory properties of p53 must be kept in check in nondamaged cells in
      order to facilitate proper embryogenesis or the homeostatic maintenance of adult
      tissues. This requisite inhibition of p53 is performed primarily by the MDM
      oncoproteins, Mdm2 and MdmX. These p53-binding proteins limit p53 activity both
      in normal cells and in stressed cells seeking to promote resolution of their p53
      stress response. Many mouse models bearing genetic alterations in Mdm2 or MdmX
      have been generated to explore the function and regulation of MDM-p53 signaling
      in development, in tissue homeostasis, in aging, and in cancer. These models not
      only have demonstrated a critical need for Mdm2 and MdmX in normal cell growth
      and in development but more recently have identified the MDM-p53 signaling axis
      as a key regulator of the cellular response to a wide variety of genetic or
      metabolic stresses. In this review, we discuss what has been learned from various
      studies of these Mdm2 and MdmX mouse models and highlight a few of the many
      important remaining questions.

PMID- 23150755
TI  - p53 Regulation Goes Live-Mdm2 and MdmX Co-Star: Lessons Learned from Mouse
      Modeling.
AB  - Classically, p53 is considered to be an overarching tumor suppressor gene,
      important in its role as a transcription factor for a number of genes critical
      for cell cycle arrest, apoptosis, and senescence. More recently, the scope of p53
      function has been further broadened, with evidence emerging that supports
      essential roles for p53 in reproduction and metabolism. The homologous proteins
      Mdm2 and MdmX function as the primary negative regulators of p53 stability and
      activity. Canonically, Mdm2 is thought to regulate p53 through 2 mechanisms: 1)
      through directly binding the p53 transactivation domain, suppressing p53
      activity, and 2) through functioning as an E3 ubiquitin ligase capable of
      ubiquitinating p53, targeting it for nuclear export and degradation. MdmX
      similarly functions to bind the p53 transactivation domain; however, it is not
      characterized to harbor any intrinsic E3 ubiquitin ligase activity. Despite
      extensive study, the advent of a number of mouse models has brought to light the
      necessity of studying the p53 pathway at physiological levels and emphasized the
      major differences that can exist between in vitro and in vivo analysis. While
      many questions remain, a focus on the use of in vivo models in p53 study is
      providing a clearer view of how this pathway is regulated, with a newfound
      emphasis on the role of the Mdm2:MdmX heterodimer, and with that a better
      understanding of how this pathway could be better manipulated for therapeutic
      gains.

PMID- 23150757
TI  - Dual Roles of MDM2 in the Regulation of p53: Ubiquitination Dependent and
      Ubiquitination Independent Mechanisms of MDM2 Repression of p53 Activity.
AB  - MDM2 oncogenic protein is the principal cellular antagonist of the p53 tumor
      suppresser gene. p53 activity needs exquisite control to elicit appropriate
      responses to differential cellular stress conditions. p53 becomes stabilized and
      active upon various types of stresses. However, too much p53 is not beneficial to
      cells and causes lethality. At the steady state, p53 activity needs to be leashed
      for cell survival. Early studies suggested that the MDM2 oncoprotein negatively
      regulates p53 activity through the induction of p53 protein degradation. MDM2
      serves as an E3 ubiquitin ligase of p53; it catalyzes polyubiquitination and
      subsequently induces proteasome degradation to downregulate p53 protein level.
      However, the mechanism by which MDM2 represses p53 is not a single mode. Emerging
      evidence reveals another cellular location of MDM2-p53 interaction. MDM2 is
      recruited to chromatin, specifically the p53 responsive promoter regions, in a
      p53 dependent manner. MDM2 is proposed to directly inhibit p53 transactivity at
      chromatin. This article provides an overview of the mechanism by which p53 is
      repressed by MDM2 in both ubiquitination dependent and ubiquitination independent
      pathways.

PMID- 23150756
TI  - The Many Faces of MDM2 Binding Partners.
AB  - Mdm2 is an essential regulator of the p53 tumor suppressor. Mdm2 is modified at
      transcriptional, post-transcriptional, and post-translational levels to control
      p53 activity in normal versus stressed cells. Importantly, errors in these
      regulatory mechanisms can result in aberrant Mdm2 expression and failure to
      initiate programmed cell death in response to DNA damage. Such errors can have
      severe consequences as evidenced by tumor phenotypes resulting from amplification
      at the Mdm2 locus and changes in post-transcriptional and post-translational
      regulation of Mdm2. Although Mdm2 mediated inhibition of p53 is well
      characterized, Mdm2 interacts with many additional proteins and also targets many
      of these for proteosomal degradation. Mdm2 also has E3-ligase independent
      functions and p53-independent functions that have important implications for
      genome stability and cancer.

PMID- 23150758
TI  - It Takes 15 to Tango: Making Sense of the Many Ubiquitin Ligases of p53.
AB  - The transcription factor p53 regulates numerous cellular processes to guard
      against tumorigenesis. Cell-cycle inhibition, apoptosis, and autophagy are all
      regulated by p53 in a cell- and context-specific manner, underscoring the need
      for p53 activity to be kept low in most circumstances. p53 is kept in check
      primarily through its regulated ubiquitination and degradation by a number of
      different factors, whose contributions may reflect complex context-specific needs
      to restrain p53 activity. Chief among these E3 ubiquitin ligases in p53
      homeostasis is the ubiquitously expressed proto-oncogene MDM2, whose loss renders
      vertebrates unable to limit p53 activity, resulting in early embryonic lethality.
      MDM2 has been validated as a critical, universal E3 ubiquitin ligase for p53 in
      numerous tissues and organisms to date, but additional E3 ligases have also been
      identified for p53 whose contribution to p53 activity is unclear. In this review,
      we summarize the recent advances in our knowledge regarding how p53 activity is
      apparently controlled by a multitude of ubiquitin ligases beyond MDM2.

PMID- 23150759
TI  - Mdm2 and MdmX as Regulators of Gene Expression.
AB  - p53 is an important tumor suppressor, functioning as a transcriptional activator
      and repressor. Upon receiving signals from multiple stress related pathways, p53
      regulates numerous activities such as cell cycle arrest, senescence, and cell
      death. When p53 activities are not required, the protein is held in check by
      interacting with 2 key homologous regulators, Mdm2 and MdmX, and a search for
      inhibitors of these interactions is well underway. However, it is now recognized
      that Mdm2 and MdmX function beyond simple inhibition of p53, and a complete
      understanding of Mdm2 and MdmX functions is ever more important. Indeed,
      increasing evidence suggests that Mdm2 and MdmX affect p53 target gene
      specificity and influence the activity of other transcription factors, and Mdm2
      itself may even function as a transcription co-factor through post-translational
      modification of chromatin. Additionally, Mdm2 affects post-transcriptional
      activities such as mRNA stability and translation of a variety of transcripts.
      Thus, Mdm2 and MdmX influence the expression of many genes through a wide variety
      of mechanisms, which are discussed in this review.

PMID- 23150760
TI  - The Roles of MDM2 and MDMX Phosphorylation in Stress Signaling to p53.
AB  - The p53 tumor suppressor is highly responsive to different physiological stresses
      such as abnormal cell proliferation, nutrient deprivation, and DNA damage.
      Distinct signaling mechanisms have evolved to activate p53, which in turn
      modulate numerous pathways to enhance fitness and survival of the organism.
      Elucidating the molecular mechanisms of these signaling events is critical for
      understanding tumor suppression by p53 and development of novel therapeutics.
      Studies in the past decade have established that MDM2 and MDMX are important
      targets of signaling input from different pathways. Here, we focus our discussion
      on MDM2 and MDMX phosphorylation, which is important for p53 activation by DNA
      damage. Investigations in this area have generated new insight into the inner
      workings of MDM2 and MDMX and underscore the importance of allosteric
      communication between different domains in achieving an efficient response to
      phosphorylation. It is likely that MDM2 and MDMX regulation by phosphorylation
      will share mechanistic similarities to other signaling hub molecules.
      Phosphorylation-independent p53 activators such as ARF and ribosomal proteins
      ultimately achieve the same outcome as phosphorylation, suggesting that they may
      induce similar changes in the structure and function of MDM2 and MDMX through
      protein-protein interactions.

PMID- 23150761
TI  - Protecting the genome from mdm2 and mdmx.
AB  - The contribution of Mdm2, and its recently identified family member Mdmx (Mdm4),
      to tumorigenesis has primarily focused on their negative regulation of the p53
      tumor suppressor. Although Mdm2 and Mdmx clearly inhibit p53, which can lead to
      tumor development, both have also been shown to affect tumorigenesis independent
      of p53. Given that Mdm2 and/or Mdmx overexpression is common and likely
      underestimated in human cancers, understanding the functions of these proteins
      beyond p53 control is critical. In recent years, new functions of Mdm2 and Mdmx
      that lead to genome instability, a hallmark of malignancy, have emerged.
      Specifically, roles in the DNA damage response that are distinct from their
      regulation of p53 have been identified. Inhibition of p53 as well as other
      components of the DNA damage response by Mdm2 and Mdmx can result in delayed DNA
      repair and increased genome instability, making Mdm2 and Mdmx a danger to the
      genome when aberrantly expressed. However, the genome instability caused by
      altered levels of Mdm2 and Mdmx could be used therapeutically for the treatment
      of cancer. Specifically, drugs/small molecules that target the interaction
      between Mdm2 and p53 can stabilize Mdm2, resulting in negative consequences on
      the genome that could be exploited for cancer treatment, particularly
      malignancies lacking functional p53.

PMID- 23150762
TI  - Concepts in MDM2 Signaling: Allosteric Regulation and Feedback Loops.
AB  - The function and regulation of MDM2 as a component of a p53-dependent negative
      feedback loop has formed a core paradigm in the p53 field. This concept, now 20
      years old, has been solidified by fields of protein science, transgenic
      technology, and drug discovery in human cancer. However, it has been noted that a
      simple negative feedback loop between p53 and MDM2 lacks an intrinsic
      "activating" step that counteracts this inhibition and permits oscillation of the
      feedback to occur as p53 is switched on and off. More recent work has identified
      a solution to the missing piece of the picture that counters the negative
      feedback loop, which is MDM2 itself. Under conditions of genotoxic stress, MDM2
      helps to activate p53 by increasing its rate of protein synthesis. This simple
      observation makes certain aspects of the p53 response more comprehensible such as
      why MDM2 is upregulated by p53 early on following DNA damage and how
      phosphorylation of MDM2 at the C-terminal Ser395 by ATM translates into p53
      activation. The latter acts by inducing allosteric changes in the RING domain of
      MDM2 that expose its RNA binding pocket, support p53 synthesis, and suppress its
      degradation. This allosteric nature of MDM2 in the C-terminus mirrors the
      allosteric effects of the binding of small molecules to the p53 interacting
      pocket at the N-terminus of MDM2, which opens the core domain of MDM2 to central
      domains of p53, which controls p53 ubiquitination. Thus, the highly allosteric
      nature of MDM2 provides the basis for dynamic protein-protein interactions and
      protein-RNA interactions through which MDM2's activity is regulated in p53
      protein destruction or in p53 protein synthesis. We discuss these mechanisms and
      how this information can be exploited for drug development programs aimed at
      activating p53 via targeting MDM2.

PMID- 23150765
TI  - Mdm2 in evolution.
AB  - While the presence, in the invertebrates, of genes related in sequence and
      function to the vertebrate p53 family has been known since the discovery of the
      fly Drosophila melanogaster Dmp53 and the worm Caenorhabditis elegans cep-1 gene,
      the failure to discover homologs of the essential vertebrate negative regulator
      of p53 Mdm2 in these species led to the false assumption that Mdm2 was only
      present in vertebrates. Very recently, clear homologs of Mdm2 have been
      discovered in a wide range of invertebrate species, raising a series of
      interesting questions about the evolution of the p53 pathway. Here, a personal
      account of the discovery of Mdm2-like genes in the Placozoa and Arthropoda is
      used to speculate on aspects of the evolution, structure, and function of the p53
      pathway.

PMID- 23150763
TI  - Scission of the p53-MDM2 Loop by Ribosomal Proteins.
AB  - The oncoprotein MDM2 is both the transcriptional target and the predominant
      antagonist of the tumor suppressor p53. MDM2 inhibits the functions of p53 via a
      negative feedback loop that can be circumvented by several ribosomal proteins in
      response to nucleolar or ribosomal stress. Stress conditions in the nucleolus can
      be triggered by a variety of extracellular and intracellular insults that impair
      ribosomal biogenesis and function, such as chemicals, nutrient deprivation, DNA
      damaging agents, or genetic alterations. The past decade has witnessed a
      tremendous progress in understanding this previously underinvestigated ribosomal
      stress-MDM2-p53 pathway. Here, we review the recent progress in understanding
      this unique signaling pathway, discuss its biological and pathological
      significance, and share with readers our insight into the research in this field.

PMID- 23150764
TI  - Splicing up mdm2 for cancer proteome diversity.
AB  - Cancer cells often have high expression of Mdm2. However, in many cancers mdm2 is
      alternatively spliced, with more than 40 mRNA variants identified. Many of the
      alternative spliced mdm2 mRNAs have the potential to encode truncated Mdm2
      isoforms. These putative Mdm2 isoforms can theoretically increase the diversity
      of the cancer proteome. The 3 best characterized are Mdm2-A, Mdm2-B, and Mdm2-C.
      As described in this review, the exogenous expression of these isoforms results
      in paradoxical phenotypes of transformation-associated growth as well as the
      inhibition of growth. Interestingly, these Mdm2 isoforms contribute tumor
      promoting capacity in p53-null backgrounds. Herein we describe how alternative
      splicing of mdm2 may result in Mdm2 protein products that alter signal
      transduction to promote tumorigenesis. The tumor promoting capacity of Mdm2
      isoforms is discussed in the context of functions that do not require the
      inhibition of p53. When N-terminal portions of Mdm2 are missing, the biochemical
      functions encoded by exon 12 are proposed to become more important. This may
      result in growth promoting functions when wild-type p53 is absent or compromised.
      The p53-independent tumor promoting activity of Mdm2 is proposed to result from C
      terminal biochemical contributions of DNA binding, RNA binding, nucleolar
      localization, and nucleotide binding.

PMID- 23150766
TI  - Equilibrium radionuclide angiocardiography: Its usefulness in current practice
      and potential future applications.
AB  - The routine and potential future applications of equilibrium radionuclide
      angiocardiography/multigated acquisition (MUGA) in clinical decision making are
      explored in this review. The non-invasive nature of the test, less operator
      dependence, lower radiation dose and ease of performing, even in ill patients,
      are important considerations in clinical cardiology practice. Two important
      routine uses of this modality in day-to-day clinical practice include the
      following: serial assessment of left ventricular ejection fraction (LVEF) in
      patients receiving cardiotoxic chemotherapy, and determination of accurate LVEF
      in patients with intractable heart failure. Other potential utilities of MUGA
      that could be translated into clinical practice include determination of regional
      LVEF, obtaining information about both right and left ventricle in suitable
      patients as a part of first pass angiocardiography, identification of diastolic
      dysfunction in patients with heart failure with preserved LVEF, and demonstration
      of dyssynchrony prior to cardiac resynchronisation, specifically by MUGA single
      photon emission tomography.The last two indications are particularly important
      and evolving at this point.

PMID- 23150767
TI  - A dose comparison survey in CT departments of dedicated paediatric hospitals in
      Australia and Saudi Arabia.
AB  - AIM: To measure and compare computed tomography (CT) radiation doses delivered to
      patients in public paediatric hospitals in Australia and Saudi Arabia. METHODS:
      Doses were measured for routine CT scans of the head, chest and abdomen/pelvis
      for children aged 3-6 years in all dedicated public paediatric hospitals in
      Australia and Saudi Arabia using a CT phantom measurement cylinder. RESULTS: CT
      doses, using the departments' protocols for 3-6 year old, varied considerably
      between hospitals. Measured head doses varied from 137.6 to 528.0 mGy(.)cm, chest
      doses from 21.9 to 92.5 mGy(.)cm, and abdomen/pelvis doses from 24.9 to 118.0
      mGy(.)cm. Mean head and abdomen/pelvis doses delivered in Saudi Arabian
      paediatric CT departments were significantly higher than those in their
      Australian equivalents. CONCLUSION: CT dose varies substantially across
      Australian and Saudi Arabian paediatric hospitals. Therefore, diagnostic
      reference levels should be established for major anatomical regions to
      standardise dose.

PMID- 23150768
TI  - Volvulus of the ascending colon in a non-rotated midgut: Plain film and MDCT
      findings.
AB  - Colonic volvulus is a relatively uncommon cause of large bowel obstruction
      usually involving mobile, intra-peritoneal, colonic segments. Congenital or
      acquired anatomic variation may be associated with an increased risk of colonic
      volvulus which can occasionally involve retro-peritoneal segments. We report a
      case of 54-year-old female who presented to our Institution to perform a plain
      abdominal film series for acute onset of cramping abdominal pain. Both the
      upright and supine films showed signs of acute colonic obstruction which was
      thought to be due to an internal hernia of the transverse colon into the lesser
      sac. The patient was therefore submitted to a multi-detector contrast-enhanced
      computed tomography (CT). CT findings were initially thought to be consistent
      with the presumed diagnosis of internal hernia but further evaluation and coronal
      reformatting clearly depicted the presence of a colonic volvulus possibly
      resulting from a retro-gastric colon. At surgery, a volvulus of the ascending
      colon was found and a right hemi-colectomy had to be performed. However, a non
      rotated midgut with a right-sided duodeno-jejunal flexure and a left sided colon
      was also found at laparotomy and overlooked in the pre-operative CT.
      Retrospective evaluation of CT images was therefore performed and a number of CT
      signs of intestinal malrotation could be identified.

PMID- 23150769
TI  - Vortex domain structure in ferroelectric nanoplatelets and control of its
      transformation by mechanical load.
AB  - Vortex domain patterns in low-dimensional ferroelectrics and multiferroics have
      been extensively studied with the aim of developing nanoscale functional devices.
      However, control of the vortex domain structure has not been investigated
      systematically. Taking into account effects of inhomogeneous electromechanical
      fields, ambient temperature, surface and size, we demonstrate significant
      influence of mechanical load on the vortex domain structure in ferroelectric
      nanoplatelets. Our analysis shows that the size and number of dipole vortices can
      be controlled by mechanical load, and yields rich temperature-stress (T-S) phase
      diagrams. Simulations also reveal that transformations between "vortex states"
      induced by the mechanical load are possible, which is totally different from the
      conventional way controlled on the vortex domain by the electric field. These
      results are relevant to application of vortex domain structures in ferroelectric
      nanodevices, and suggest a novel route to applications including memories,
      mechanical sensors and transducers.

PMID- 23150770
TI  - Leidenfrost levitation: beyond droplets.
AB  - Friction is a major inhibitor in almost every mechanical system. Enlightened by
      the Leidenfrost effect - a droplet can be levitated by its own vapor layer on a
      sufficiently hot surface - we demonstrate for the first time that a small cart
      can also be levitated by Leidenfrost vapor. The levitated cart can carry certain
      amount of load and move frictionlessly over the hot surface. The maximum load
      that the cart can carry is experimentally tested over a range of surface
      temperatures. We show that the levitated cart can be propelled not only by
      gravitational force over a slanted flat surface, but also self-propelled over a
      ratchet shaped horizontal surface. In the end, we experimentally tested water
      consumption rate for sustaining the levitated cart, and compared the results to
      theoretical calculations. If perfected, this frictionless Leidenfrost cart could
      be used in numerous engineering applications where relative motion exists between
      surfaces.

PMID- 23150771
TI  - Obesity-induced endoplasmic reticulum stress causes chronic inflammation in
      adipose tissue.
AB  - Adipose tissue plays a central role in maintaining metabolic homeostasis under
      normal conditions. Metabolic diseases such as obesity and type 2 diabetes are
      often accompanied by chronic inflammation and adipose tissue dysfunction. In this
      study, we observed that endoplasmic reticulum (ER) stress and the inflammatory
      response occurred in adipose tissue of mice fed a high-fat diet for a period of
      16 weeks. After 16 weeks of feeding, ER stress markers increased and chronic
      inflammation occurred in adipose tissue. We found that ER stress is induced by
      free fatty acid (FFA)-mediated reactive oxygen species (ROS) generation and up
      regulated gene expression of inflammatory cytokines in 3T3-L1 adipocytes. Oral
      administration to obese mice of chemical chaperons, which alleviate ER stress,
      improved chronic inflammation in adipose tissue, followed by the suppression of
      increased body weight and improved insulin signaling. These results indicate that
      ER stress plays important pathophysiological roles in obesity-induced adipose
      tissue dysfunction.

PMID- 23150772
TI  - You mob my owl, I'll mob yours: birds play tit-for-tat game.
AB  - Reciprocity is fundamental to cooperative behaviour and has been verified in
      theoretical models. However, there is still limited experimental evidence for
      reciprocity in non-primate species. Our results more decisively clarify that
      reciprocity with a tit-for-tat enforcement strategy can occur among breeding pied
      flycatchers Ficedula hypoleuca separate from considerations of byproduct
      mutualism. Breeding pairs living in close proximity (20-24 m) did exhibit
      byproduct mutualism and always assisted in mobbing regardless of their
      neighbours' prior actions. However, breeding pairs with distant neighbours (69-84
      m) either assisted or refused to assist in mobbing a predatory owl based on
      whether or not the distant pair had previously helped them in their own nest
      defense against the predator. Clearly, these birds are aware of their specific
      spatial security context, remember their neighbours' prior behaviour, and choose
      a situation-specific strategic course of action, which could promote their longer
      term security, a capacity previously thought unique to primates.

PMID- 23150773
TI  - Differential network entropy reveals cancer system hallmarks.
AB  - The cellular phenotype is described by a complex network of molecular
      interactions. Elucidating network properties that distinguish disease from the
      healthy cellular state is therefore of critical importance for gaining systems
      level insights into disease mechanisms and ultimately for developing improved
      therapies. By integrating gene expression data with a protein interaction network
      we here demonstrate that cancer cells are characterised by an increase in network
      entropy. In addition, we formally demonstrate that gene expression differences
      between normal and cancer tissue are anticorrelated with local network entropy
      changes, thus providing a systemic link between gene expression changes at the
      nodes and their local correlation patterns. In particular, we find that genes
      which drive cell-proliferation in cancer cells and which often encode oncogenes
      are associated with reductions in network entropy. These findings may have
      potential implications for identifying novel drug targets.

PMID- 23150774
TI  - Assignment and secondary structure of the YadA membrane protein by solid-state
      MAS NMR.
AB  - We report the complete solid-state MAS NMR resonance assignment of a medium
      sized, trimeric membrane protein, YadA-M. The protein YadA (Yersinia adhesin A)
      is an important virulence factor of enteropathogenic Yersinia species (such as
      Yersinia enterocolitica and Yersinia pseudotuberculosis). YadA is localized on
      the bacterial cell surface and is involved in adhesion to host cells and tissues.
      It is anchored in the outer membrane by a transmembrane anchor domain (YadA-M).
      This domain hosts the so-called autotransporter function of YadA: it transports
      its own N-terminal domain through the outer membrane. The assignment is based on
      a dataset that consisted of several MAS NMR correlation spectra, recorded on a
      single, uniformly (13)C, (15)N- labelled microcrystalline preparation. Except for
      the single C-terminal residue and the mobile strep tag, we were able to
      completely assign YadA-M. From this, secondary structure elements were predicted,
      which, combined with several long-range interstrand restraints, yielded the
      architecture of the beta-sheet.

PMID- 23150775
TI  - White Band Disease transmission in the threatened coral, Acropora cervicornis.
AB  - The global rise in coral diseases has severely impacted coral reef ecosystems,
      yet often little is known about these diseases, including how they are
      transmitted. White Band Disease (WBD), for example, has caused unparalleled
      declines in live Acropora cover, spreading rapidly throughout the Caribbean by
      unknown means. Here we test four putative modes of WBD transmission to the
      staghorn coral Acropora cervicornis: two animal vectors (Coralliophila abbreviata
      and C. caribaea) and waterborne transmission to intact and injured coral tissues.
      Using aquarium-based infection experiments, we determine that C. abbreviata, but
      not C. caribaea, acts as both a vector and reservoir for transmission of the WBD
      pathogen. We also demonstrate waterborne transmission to injured, but not intact
      staghorn coral tissues. The combination of transmission by both animal vectors
      and through the water column helps explain how WBD is spread locally and across
      the Caribbean.

PMID- 23150776
TI  - Dishevelled3 is a novel arginine methyl transferase substrate.
AB  - Dishevelled, a phosphoprotein scaffold, is a central component in all the Wnt
      sensitive signaling pathways. In the present study, we report that Dishevelled is
      post-translationally modified, both in vitro and in vivo, via arginine
      methylation. We also show protein arginine methyl transferases 1 and 7 as the key
      enzymes catalyzing Dishevelled methylation. Interestingly, Wnt3a stimulation of
      F9 teratocarcinoma cells results in reduced Dishevelled methylation. Similarly,
      the methylation-deficient mutant of Dishevelled, R271K, displayed spontaneous
      membrane localization and robust activation of Wnt signaling; suggesting that
      differential methylation of Dishevelled plays an important role in Wnt signaling.
      Thus arginine methylation is shown to be an important switch in regulation of
      Dishevelled function and Wnt signaling.

PMID- 23150777
TI  - APOBEC3B can impair genomic stability by inducing base substitutions in genomic
      DNA in human cells.
AB  - Human APOBEC3 proteins play pivotal roles in intracellular defense against viral
      infection by catalyzing deamination of cytidine residues, leading to base
      substitutions in viral DNA. Activation-induced cytidine deaminase (AID), another
      member of the APOBEC family, is capable of editing immunoglobulin (Ig) and non-Ig
      genes, and aberrant expression of AID leads to tumorigenesis. However, it remains
      unclear whether APOBEC3 (A3) proteins affect stability of human genome. Here we
      demonstrate that both A3A and A3B can induce base substitutions into human genome
      as AID can. A3B is highly expressed in several lymphoma cells and somatic
      mutations occur in some oncogenes of the cells highly expressing A3B.
      Furthermore, transfection of A3B gene into lymphoma cells induces base
      substitutions in cMYC gene. These data suggest that aberrant expression of A3B
      can evoke genomic instability by inducing base substitutions into human genome,
      which might lead to tumorigenesis in human cells.

PMID- 23150778
TI  - Hapten mediated display and pairing of recombinant antibodies accelerates assay
      assembly for biothreat countermeasures.
AB  - A bottle-neck in recombinant antibody sandwich immunoassay development is
      pairing, demanding protein purification and modification to distinguish captor
      from tracer. We developed a simple pairing scheme using microliter amounts of E.
      coli osmotic shockates bearing site-specific biotinylated antibodies and
      demonstrated proof of principle with a single domain antibody (sdAb) that is both
      captor and tracer for polyvalent Marburgvirus nucleoprotein. The system could
      also host pairs of different sdAb specific for the 7 botulinum neurotoxin (BoNT)
      serotypes, enabling recognition of the cognate serotype. Inducible supE co
      expression enabled sdAb populations to be propagated as either phage for more
      panning from repertoires or expressed as soluble sdAb for screening within a
      single host strain. When combined with streptavidin-g3p fusions, a novel
      transdisplay system was formulated to retrofit a semi-synthetic sdAb library
      which was mined for an anti-Ebolavirus sdAb which was immediately immunoassay
      ready, thereby speeding up the recombinant antibody discovery and utilization
      processes.

PMID- 23150779
TI  - The miR-290-295 cluster suppresses autophagic cell death of melanoma cells.
AB  - We compared the expression levels of 307 miRNAs in six different B16F1 melanoma
      cell lines of differing malignant properties and found that the miR-290-295
      cluster showed a strong upregulation in the more malignant B16F1 daughter cell
      lines. Its overexpression in B16F1 cells had no major effects on cell
      proliferation, migration or anchorage-independent growth, but conferred
      resistance to glucose starvation. This was mediated by miR-290-295-induced
      downregulation of several essential autophagy genes, including Atg7 and ULK1,
      which resulted in inhibition of autophagic cell death induced by glucose
      starvation. Similar effects were observed after knockdown of Atg7 or ULK1 in
      B16F1 melanoma cells, and after treatment with two chemical inhibitors of
      autophagy. Together, these results indicate that autophagy mediates cell death of
      melanoma cells under chronic nutrient deprivation, and they reveal an
      unanticipated role of the miR-290-295 cluster in conferring a survival advantage
      to melanoma cells by inhibiting autophagic cell death.

PMID- 23150780
TI  - Surface-plasmon-enhanced deep-UV light emitting diodes based on AlGaN multi
      quantum wells.
AB  - We report the development of complete structural AlGaN-based deep-ultraviolet
      light-emitting diodes with an aluminum thin layer for increasing light extraction
      efficiency. A 217% enhancement in peak photoluminescence intensity at 294 nm is
      observed. Cathodoluminescence measurement demonstrates that the internal quantum
      efficiency of the deep-UV LEDs coated with Al layer is not enhanced. The emission
      enhancement of deep-UV LEDs is attributed to the higher LEE by the surface
      plasmon-transverse magnetic wave coupling. When the proportion of the TM wave to
      the Al layer increases with the Al content in the Al(x)Ga(1-x)N multiple quantum
      wells, i.e., the band edge emission energy, the enhancement ratio of the Al
      coated deep-UV LEDs increases.

PMID- 23150781
TI  - A monolithically integrated polarization entangled photon pair source on a
      silicon chip.
AB  - Integrated photonic circuits are one of the most promising platforms for large
      scale photonic quantum information systems due to their small physical size and
      stable interferometers with near-perfect lateral-mode overlaps. Since many
      quantum information protocols are based on qubits defined by the polarization of
      photons, we must develop integrated building blocks to generate, manipulate, and
      measure the polarization-encoded quantum state on a chip. The generation unit is
      particularly important. Here we show the first integrated polarization-entangled
      photon pair source on a chip. We have implemented the source as a simple and
      stable silicon-on-insulator photonic circuit that generates an entangled state
      with 91 +/- 2% fidelity. The source is equipped with versatile interfaces for
      silica-on-silicon or other types of waveguide platforms that accommodate the
      polarization manipulation and projection devices as well as pump light sources.
      Therefore, we are ready for the full-scale implementation of photonic quantum
      information systems on a chip.

PMID- 23150783
TI  - Asymmetric light propagation in composition-graded semiconductor nanowires.
AB  - Asymmetric light propagation is crucial to the development of optical-based
      functional components in nanophotonics. Diverse configurations and structures
      have been proposed to allow asymmetrical propagation of photonic signal, but on
      chip integration is difficult to achieve due to their complex structure and/or
      relatively large footprint. Here we report the first design and realization of
      asymmetric light propagation in single semiconductor nanowires with a composition
      gradient along the length. We show the asymmetric nanowire waveguides can be
      synthesized using a simple thermal evaporation and vapor transport approach
      without involving complicated and costly fabrication processes. Our studies
      demonstrate the asymmetric nanowire waveguides offer some significant advantages
      over previous designs, including ultra-low operation power, tunable working
      wavelength and nanoscale footprint, making them attractive building blocks for
      integrated photonic circuits.

PMID- 23150782
TI  - Optical trapping, driving, and arrangement of particles using a tapered fibre
      probe.
AB  - The ability of manipulating mesoscopic objects with high precision and
      flexibility is extremely important for a wide variety of fields from physics,
      biochemistry, to biomedicine. Particularly, the ability of arranging
      particles/cells into desired patterns precisely is a challenge for numerous
      physical and biological applications. Here, we report a strategy of realizing
      highly flexible trapping, driving, and precise arrangement of particles using a
      tapered fibre probe. Using randomly distributed 3-um-diameter silica particles as
      an example, we demonstrate that the strategy is able to stably trap the particles
      and drive them to targeted regions, subsequently arrange the particles into
      desired patterns. To further demonstrate the ability of this strategy,
      experiments were done using sub-micron sized particles and biological samples
      (bacteria and cells). This strategy provides a new approach to manipulate
      mesoscopic objects precisely and flexibly, and hopefully can be used in future
      fundamental and applied researches of interdiscipline.

PMID- 23150784
TI  - Biomaterial evolution parallels behavioral innovation in the origin of orb-like
      spider webs.
AB  - Correlated evolution of traits can act synergistically to facilitate organism
      function. But, what happens when constraints exist on the evolvability of some
      traits, but not others? The orb web was a key innovation in the origin of >12,000
      species of spiders. Orb evolution hinged upon the origin of novel spinning
      behaviors and innovations in silk material properties. In particular, a new major
      ampullate spidroin protein (MaSp2) increased silk extensibility and toughness,
      playing a critical role in how orb webs stop flying insects. Here, we show
      convergence between pseudo-orb-weaving Fecenia and true orb spiders. As in the
      origin of true orbs, Fecenia dragline silk improved significantly compared to
      relatives. But, Fecenia silk lacks the high compliance and extensibility found in
      true orb spiders, likely due in part to the absence of MaSp2. Our results suggest
      how constraints limit convergent evolution and provide insight into the evolution
      of nature's toughest fibers.

PMID- 23150785
TI  - Comparing the performance of FA, DFA and DMA using different synthetic long-range
      correlated time series.
AB  - Notwithstanding the significant efforts to develop estimators of long-range
      correlations (LRC) and to compare their performance, no clear consensus exists on
      what is the best method and under which conditions. In addition, synthetic tests
      suggest that the performance of LRC estimators varies when using different
      generators of LRC time series. Here, we compare the performances of four
      estimators [Fluctuation Analysis (FA), Detrended Fluctuation Analysis (DFA),
      Backward Detrending Moving Average (BDMA), and Centred Detrending Moving Average
      (CDMA)]. We use three different generators [Fractional Gaussian Noises, and two
      ways of generating Fractional Brownian Motions]. We find that CDMA has the best
      performance and DFA is only slightly worse in some situations, while FA performs
      the worst. In addition, CDMA and DFA are less sensitive to the scaling range than
      FA. Hence, CDMA and DFA remain "The Methods of Choice" in determining the Hurst
      index of time series.

PMID- 23150786
TI  - Virus-induced gene complementation reveals a transcription factor network in
      modulation of tomato fruit ripening.
AB  - Plant virus technology, in particular virus-induced gene silencing, is a widely
      used reverse- and forward-genetics tool in plant functional genomics. However the
      potential of virus technology to express genes to induce phenotypes or to
      complement mutants in order to understand the function of plant genes is not well
      documented. Here we exploit Potato virus X as a tool for virus-induced gene
      complementation (VIGC). Using VIGC in tomato, we demonstrated that ectopic viral
      expression of LeMADS-RIN, which encodes a MADS-box transcription factor (TF),
      resulted in functional complementation of the non-ripening rin mutant phenotype
      and caused fruits to ripen. Comparative gene expression analysis indicated that
      LeMADS-RIN up-regulated expression of the SBP-box (SQUAMOSA promoter binding
      protein-like) gene LeSPL-CNR, but down-regulated the expression of LeHB-1, an HD
      Zip homeobox TF gene. Our data support the hypothesis that a transcriptional
      network may exist among key TFs in the modulation of fruit ripening in tomato.

PMID- 23150787
TI  - Time-gated orthogonal scanning automated microscopy (OSAM) for high-speed cell
      detection and analysis.
AB  - We report a new development of orthogonal scanning automated microscopy (OSAM)
      incorporating time-gated detection to locate rare-event organisms regardless of
      autofluorescent background. The necessity of using long-lifetime (hundreds of
      microseconds) luminescent biolabels for time-gated detection implies long
      integration (dwell) time, resulting in slow scan speed. However, here we achieve
      high scan speed using a new 2-step orthogonal scanning strategy to realise on-the
      fly time-gated detection and precise location of 1-MUm lanthanide-doped
      microspheres with signal-to-background ratio of 8.9. This enables analysis of a
      15 mm * 15 mm slide area in only 3.3 minutes. We demonstrate that detection of
      only a few hundred photoelectrons within 100 MUs is sufficient to distinguish a
      target event in a prototype system using ultraviolet LED excitation. Cytometric
      analysis of lanthanide labelled Giardia cysts achieved a signal-to-background
      ratio of two orders of magnitude. Results suggest that time-gated OSAM represents
      a new opportunity for high-throughput background-free biosensing applications.

PMID- 23150789
TI  - Nano-materials enabled thermoelectricity from window glasses.
AB  - With a projection of nearly doubling up the world population by 2050, we need
      wide variety of renewable and clean energy sources to meet the increased energy
      demand. Solar energy is considered as the leading promising alternate energy
      source with the pertinent challenge of off sunshine period and uneven worldwide
      distribution of usable sun light. Although thermoelectricity is considered as a
      reasonable renewable energy from wasted heat, its mass scale usage is yet to be
      developed. Here we show, large scale integration of nano-manufactured pellets of
      thermoelectric nano-materials, embedded into window glasses to generate
      thermoelectricity using the temperature difference between hot outside and cool
      inside. For the first time, this work offers an opportunity to potentially
      generate 304 watts of usable power from 9 m(2) window at a 20 degrees C
      temperature gradient. If a natural temperature gradient exists, this can serve as
      a sustainable energy source for green building technology.

PMID- 23150788
TI  - BDNF gene therapy induces auditory nerve survival and fiber sprouting in deaf
      Pou4f3 mutant mice.
AB  - Current therapy for patients with hereditary absence of cochlear hair cells, who
      have severe or profound deafness, is restricted to cochlear implantation, a
      procedure that requires survival of the auditory nerve. Mouse mutations that
      serve as models for genetic deafness can be utilized for developing and enhancing
      therapies for hereditary deafness. A mouse with Pou4f3 loss of function has no
      hair cells and a subsequent, progressive degeneration of auditory neurons. Here
      we tested the influence of neurotrophin gene therapy on auditory nerve survival
      and peripheral sprouting in Pou4f3 mouse ears. BDNF gene transfer enhanced
      preservation of auditory neurons compared to control ears, in which nearly all
      neurons degenerated. Surviving neurons in treated ears exhibited pronounced
      sprouting of nerve fibers into the auditory epithelium, despite the absence of
      hair cells. This enhanced nerve survival and regenerative sprouting may improve
      the outcome of cochlear implant therapy in patients with hereditary deafness.

PMID- 23150790
TI  - MicroRNA-mediated mRNA translation activation in quiescent cells and oocytes
      involves recruitment of a nuclear microRNP.
AB  - MicroRNAs can promote translation of specific mRNAs in quiescent (G0) mammalian
      cells and immature Xenopus laevis oocytes. We report that microRNA-mediated
      upregulation of target mRNAs in oocytes is dependent on nuclear entry of the
      microRNA; cytoplasmically-injected microRNA repress target mRNAs. Components of
      the activation microRNP, AGO, FXR1 (FXR1-iso-a) and miR16 are present in the
      nucleus and cytoplasm. Importantly, microRNA target mRNAs for upregulation, Myt1,
      TNFalpha and a reporter bearing the TNFalpha AU-rich, microRNA target sequence,
      are associated with AGO in immature oocyte nuclei and AGO2 in G0 human nuclei,
      respectively. mRNAs that are repressed or lack target sites are not associated
      with nuclear AGO. Crosslinking-coupled immunopurification revealed greater
      association of AGO2 with FXR1 in the nucleus compared to cytoplasm. Consistently,
      overexpression of FXR1-iso-a rescues activation of cytoplasmically-injected RNAs
      and in low density, proliferating cells. These data indicate the importance of a
      compartmentalized AGO2-FXR1-iso-a complex for selective recruitment for microRNA
      mediated upregulation.

PMID- 23150792
TI  - The evolution of homophily.
AB  - Biologists have devoted much attention to assortative mating or homogamy, the
      tendency for sexual species to mate with similar others. In contrast, there has
      been little theoretical work on the broader phenomenon of homophily, the tendency
      for individuals to interact with similar others. Yet this behaviour is also
      widely observed in nature. Here, we model how natural selection can give rise to
      homophily when individuals engage in social interaction in a population with
      multiple observable phenotypes. Payoffs to interactions depend on whether or not
      individuals have the same or different phenotypes, and each individual has a
      preference that determines how likely they are to interact with others of their
      own phenotype (homophily) or of opposite phenotypes (heterophily). The results
      show that homophily tends to evolve under a wide variety of conditions, helping
      to explain its ubiquity in nature.

PMID- 23150791
TI  - GTPases IF2 and EF-G bind GDP and the SRL RNA in a mutually exclusive manner.
AB  - Translational GTPases (trGTPases) are involved in all four stages of protein
      biosynthesis: initiation, elongation, termination and ribosome recycling. The
      trGTPases Initiation Factor 2 (IF2) and Elongation Factor G (EF-G) respectively
      orchestrate initiation complex formation and translocation of the peptidyl
      tRNA:mRNA complex through the bacterial ribosome. The ribosome regulates the
      GTPase cycle and efficiently discriminates between the GDP- and GTP-bound forms
      of these proteins. Using Isothermal Titration Calorimetry, we have investigated
      interactions of IF2 and EF-G with the sarcin-ricin loop of the 23S rRNA, a
      crucial element of the GTPase-associated center of the ribosome. We show that
      binding of IF2 and EF-G to a 27 nucleotide RNA fragment mimicking the sarcin
      ricin loop is mutually exclusive with that of GDP, but not of GTP, providing a
      mechanism for destabilization of the ribosome-bound GDP forms of translational
      GTPases.

PMID- 23150793
TI  - Effects of gestational age and surface modification on materno-fetal transfer of
      nanoparticles in murine pregnancy.
AB  - Nanoparticle exposure in pregnancy may result in placental damage and
      fetotoxicity; however, the factors that determine fetal nanoparticle exposure are
      unclear. Here we have assessed the effect of gestational age and nanoparticle
      composition on fetal accumulation of maternally-administered nanomaterials in
      mice. We determined the placental and fetal uptake of 13 nm gold nanoparticles
      with different surface modifications (ferritin, PEG and citrate) following
      intravenous administration at E5.5-15.5. We showed that prior to E11.5, all
      tested nanoparticles could be visualized and detected in fetal tissues in
      significant amounts; however, fetal gold levels declined dramatically post-E11.5.
      In contrast, Au-nanoparticle accumulation in the extraembryonic tissues (EET)
      increased 6-15 fold with gestational age. Fetal and EET accumulation of ferritin-
      and PEG-modified nanoparticles was considerably greater than citrate-capped
      nanoparticles. No signs of toxicity were observed. Fetal exposure to
      nanoparticles in murine pregnancy is, therefore, influenced by both stage of
      embryonic/placental maturation and nanoparticle surface composition.

PMID- 23150794
TI  - A novel role for lipid droplets in the organismal antibacterial response.
AB  - We previously discovered histones bound to cytosolic lipid droplets (LDs); here
      we show that this forms a cellular antibacterial defense system. Sequestered on
      droplets under normal conditions, in the presence of bacterial lipopolysaccharide
      (LPS) or lipoteichoic acid (LTA), histones are released from the droplets and
      kill bacteria efficiently in vitro. Droplet-bound histones also function in vivo:
      when injected into Drosophila embryos lacking droplet-bound histones, bacteria
      grow rapidly. In contrast, bacteria injected into embryos with droplet-bound
      histones die. Embryos with droplet-bound histones displayed more than a fourfold
      survival advantage when challenged with four different bacterial species. Our
      data suggests that this intracellular antibacterial defense system may function
      in adult flies, and also potentially in
      mice.DOI:http://dx.doi.org/10.7554/eLife.00003.001.

PMID- 23150795
TI  - Nascent-Seq reveals novel features of mouse circadian transcriptional regulation.
AB  - A substantial fraction of the metazoan transcriptome undergoes circadian
      oscillations in many cells and tissues. Based on the transcription feedback loops
      important for circadian timekeeping, it is commonly assumed that this mRNA
      cycling reflects widespread transcriptional regulation. To address this issue, we
      directly measured the circadian dynamics of mouse liver transcription using
      Nascent-Seq (genome-wide sequencing of nascent RNA). Although many genes are
      rhythmically transcribed, many rhythmic mRNAs manifest poor transcriptional
      rhythms, indicating a prominent contribution of post-transcriptional regulation
      to circadian mRNA expression. This analysis of rhythmic transcription also showed
      that the rhythmic DNA binding profile of the transcription factors CLOCK and
      BMAL1 does not determine the transcriptional phase of most target genes. This
      likely reflects gene-specific collaborations of CLK:BMAL1 with other
      transcription factors. These insights from Nascent-Seq indicate that it should
      have broad applicability to many other gene expression regulatory
      issues.DOI:http://dx.doi.org/10.7554/eLife.00011.001.

PMID- 23150796
TI  - Sodium taurocholate cotransporting polypeptide is a functional receptor for human
      hepatitis B and D virus.
AB  - Human hepatitis B virus (HBV) infection and HBV-related diseases remain a major
      public health problem. Individuals coinfected with its satellite hepatitis D
      virus (HDV) have more severe disease. Cellular entry of both viruses is mediated
      by HBV envelope proteins. The pre-S1 domain of the large envelope protein is a
      key determinant for receptor(s) binding. However, the identity of the receptor(s)
      is unknown. Here, by using near zero distance photo-cross-linking and tandem
      affinity purification, we revealed that the receptor-binding region of pre-S1
      specifically interacts with sodium taurocholate cotransporting polypeptide
      (NTCP), a multiple transmembrane transporter predominantly expressed in the
      liver. Silencing NTCP inhibited HBV and HDV infection, while exogenous NTCP
      expression rendered nonsusceptible hepatocarcinoma cells susceptible to these
      viral infections. Moreover, replacing amino acids 157-165 of nonfunctional monkey
      NTCP with the human counterpart conferred its ability in supporting both viral
      infections. Our results demonstrate that NTCP is a functional receptor for HBV
      and HDV.DOI:http://dx.doi.org/10.7554/eLife.00049.001.

PMID- 23150797
TI  - Non-canonical TAF complexes regulate active promoters in human embryonic stem
      cells.
AB  - The general transcription factor TFIID comprises the TATA-box-binding protein
      (TBP) and approximately 14 TBP-associated factors (TAFs). Here we find,
      unexpectedly, that undifferentiated human embryonic stem cells (hESCs) contain
      only six TAFs (TAFs 2, 3, 5, 6, 7 and 11), whereas following differentiation all
      TAFs are expressed. Directed and global chromatin immunoprecipitation analyses
      reveal an unprecedented promoter occupancy pattern: most active genes are bound
      by only TAFs 3 and 5 along with TBP, whereas the remaining active genes are bound
      by TBP and all six hESC TAFs. Consistent with these results, hESCs contain a
      previously undescribed complex comprising TAFs 2, 6, 7, 11 and TBP. Altering the
      composition of hESC TAFs, either by depleting TAFs that are present or
      ectopically expressing TAFs that are absent, results in misregulated expression
      of pluripotency genes and induction of differentiation. Thus, the selective
      expression and use of TAFs underlies the ability of hESCs to self
      renew.DOI:http://dx.doi.org/10.7554/eLife.00068.001.

PMID- 23150799
TI  - Getting to grips with hepatitis.
AB  - The receptor that allows hepatitis B and hepatitis D viruses to enter human liver
      cells has been identified as a protein that transports bile acids in the liver.

PMID- 23150798
TI  - Membrane immersion allows rhomboid proteases to achieve specificity by reading
      transmembrane segment dynamics.
AB  - Rhomboid proteases reside within cellular membranes, but the advantage of this
      unusual environment is unclear. We discovered membrane immersion allows
      substrates to be identified in a fundamentally-different way, based initially
      upon exposing 'masked' conformational dynamics of transmembrane segments rather
      than sequence-specific binding. EPR and CD spectroscopy revealed that the
      membrane restrains rhomboid gate and substrate conformation to limit proteolysis.
      True substrates evolved intrinsically-unstable transmembrane helices that both
      become unstructured when not supported by the membrane, and facilitate
      partitioning into the hydrophilic, active-site environment. Accordingly,
      manipulating substrate and gate dynamics in living cells shifted cleavage sites
      in a manner incompatible with extended sequence binding, but correlated with a
      membrane-and-helix-exit propensity scale. Moreover, cleavage of diverse non
      substrates was provoked by single-residue changes that destabilize transmembrane
      helices. Membrane immersion thus bestows rhomboid proteases with the ability to
      identify substrates primarily based on reading their intrinsic transmembrane
      dynamics.DOI:http://dx.doi.org/10.7554/eLife.00173.001.

PMID- 23150800
TI  - Histones join the fight against bacteria inside cells.
AB  - Experiments on Drosophila have shown that the histones that are normally bound to
      lipid droplets inside cells can be released to provide protection against
      infection.

PMID- 23150801
TI  - The use of cellular technologies in treatment of liver pathologies.
AB  - Cell techniques find increasing application in modern clinical practice. The II
      and III phases of clinical trials are already under way for various cellular
      products used for the restoration of the functions of the cornea, larynx, skin,
      etc. However, the obtainment of functional cell types specific to different
      organs and tissues still remains a subject of laboratory research. Liver is one
      of the most important organs; the problems and prospects of cellular therapy for
      liver pathologies are currently being actively studied. Cellular therapy of liver
      pathologies is a complex multistage process requiring a thorough understanding of
      the molecular mechanisms occurring in liver cells during differentiation and
      regeneration. An analysis of the current cellular therapy for liver pathologies
      is presented, the use of various cell types is described, the main molecular
      mechanisms of hepatocyte differentiation are analyzed, and the challenges and
      prospects of cell therapy for liver disorders are discussed in this review.

PMID- 23150802
TI  - Receptor properties and features of cytokinin signaling.
AB  - Cytokinins belong to one of the most important and well-known classes of plant
      hormones. Discovered over half a century ago, cytokinins have retained the
      attention of researchers due to the variety of the effects they have on the
      growth and development of vegetable organisms, their participation in a plant
      adaptation to external conditions, and the potential to be used in biotechnology,
      agriculture, medicine and even cosmetics. The molecular mechanism by which
      cytokinins function remained unknown for a long time. Things started to change
      only in the 21(st)century, after the discovery of the receptors for these
      phytohormones. It appeared that plants found ways to adapt a two-component signal
      transduction system borrowed from prokaryotic organisms for cytokinin signalling.
      This review covers the recent advances in research of the molecular basis for the
      perception and transduction of the cytokinin signal. Emphasis is placed on
      cytokinin receptors, their domain and three-dimensional structures, subcellular
      localization, signalling activity, effect of mutations, ligand-binding
      properties, and phylogeny.

PMID- 23150803
TI  - Lipopolysaccharide of Yersinia pestis, the Cause of Plague: Structure, Genetics,
      Biological Properties.
AB  - The present review summarizes data pertaining to the composition and structure of
      the carbohydrate moiety (core oligosaccharide) and lipid component (lipid A) of
      the various forms of lipopolysaccharide (LPS), one of the major pathogenicity
      factors ofYersinia pestis, the cause of plague. The review addresses the
      functions and the biological significance of genes for the biosynthesis of LPS,
      as well as the biological properties of LPS in strains from various intraspecies
      groups ofY. pestis and their mutants, including the contribution of LPS to the
      resistance of bacteria to factors of the innate immunity of both insect-vectors
      and mammal-hosts. Special attention is paid to temperature-dependent variations
      in the LPS structure, their genetic control and roles in the pathogenesis of
      plague. The evolutionary aspect is considered based on a comparison of the
      structure and genetics of the LPS ofY. pestis and other enteric bacteria,
      including otherYersinia species. The prospects of development of live plague
      vaccines created on the basis ofY. pestis strains with the genetically modified
      LPS are discussed.

PMID- 23150804
TI  - A Polygenic Approach to the Study ?of Polygenic Diseases.
AB  - Polygenic diseases are caused by the joint contribution of a number of
      independently acting or interacting polymorphic genes; the individual
      contribution of each gene may be small or even unnoticeable. The carriage of
      certain combinations of genes can determine the occurrence of clinically
      heterogeneous forms of the disease and treatment efficacy. This review describes
      the approaches used in a polygenic analysis of data in medical genomics, in
      particular, pharmacogenomics, aimed at identifying the cumulative effect of
      genes. This effect may result from the summation of gains of different genes or
      be caused by the epistatic interaction between the genes. Both cases are
      undoubtedly of great interest in investigating the nature of polygenic diseases.
      The means that allow one to discriminate between these two possibilities are
      discussed. The methods for searching for combinations of alleles of different
      genes associated with the polygenic phenotypic traits of the disease, as well as
      the methods for presenting and validating the results, are described and
      compared. An attempt is made to evaluate the applicability of the existing
      methods to an epistasis analysis. The results obtained by the authors using the
      APSampler software are described and summarized.

PMID- 23150805
TI  - Cardiological biopharmaceuticals in the conception of drug targeting delivery:
      practical results and research perspectives.
AB  - The results of the clinical use of thrombolytic and antithrombotic preparations
      developed on the basis of protein conjugates obtained within the framework of the
      conception of drug targeting delivery in the organism are considered. A decrease
      has been noted in the number of biomedical projects focused on these derivatives
      as a result of various factors: the significant depletion of financial and
      organizational funds, the saturation of the pharmaceutical market with
      preparations of this kind, and the appearance of original means for
      interventional procedures. Factors that actively facilitate the conspicuous
      potentiation of the efficacy of bioconjugates were revealed: the biomedical
      testing of protein domains and their selected combinations, the optimization of
      molecular sizes for the bioconjugates obtained, the density of target
      localization, the application of cell adhesion molecules as targets, and the
      application of connected enzyme activities. Enzyme antioxidants and the
      opportunity for further elaboration of the drug delivery conception via the
      elucidation and formation of therapeutic targets for effective drug reactions by
      means of pharmacological pre- and postconditioning of myocardium arouse
      significant interest.

PMID- 23150806
TI  - Non-thermal Plasma Causes p53-Dependent Apoptosis in Human Colon Carcinoma Cells.
AB  - Non-thermal plasma (NTP) consists of a huge amount of biologically active
      particles, whereas its temperature is close to ambient. This combination allows
      one to use NTP as a perspective tool for solving different biomedical tasks,
      including antitumor therapy. The treatment of tumor cells with NTP caused dose
      dependent effects, such as growth arrest and apoptosis. However, while the
      outcome of NTP treatment has been established, the molecular mechanisms of the
      interaction between NTP and eukaryotic cells have not been thoroughly studied
      thus far. In this work, the mechanisms and the type of death of human colon
      carcinoma HCT 116 cells upon application of non-thermal argon plasma were
      studied. The effect of NTP on the major stress-activated protein p53 was
      investigated. The results demonstrate that the viability of HCT116 cells upon
      plasma treatment is dependent on the functional p53 protein. NTP treatment caused
      an increase in the intracellular concentration of p53 and the induction of the
      p53-controlled regulon. The p53-dependent accumulation of active proapoptotic
      caspase-3 was shown in NTP-treated cells. The study was the first to demonstrate
      that treatment of human colon carcinoma cells with NTP results in p53-dependent
      apoptosis. The results obtained contribute to our understanding of the
      applicability of NTP in antitumor therapy.

PMID- 23150807
TI  - Mitochondrial Pathway of alpha-Tocopheryl Succinate-Induced Apoptosis in Human
      Epidermoid Carcinoma A431 Cells.
AB  - Vitamin E derivatives are known to act as agents exhibiting cytotoxity against
      tumor cells. The effect of vitamin E succinate on human epidermoid carcinoma cell
      line A431 was investigated in this study using live imaging, immunocytochemistry,
      and transmission electron microscopy. alpha-Tocopheryl succinate-induced
      apoptotic cell death in A431 cells was shown to be both dose- and time-dependent.
      The hyperproduction of reactive oxygen species, changes in size, shape and
      ultrastructural characteristics of mitochondria followed by the release of
      cytochromecfrom mitochondria to cytosol were observed. These results suggest that
      alpha-tocopheryl succinate induces apoptosis that occurs via the mitochondrial
      pathway. Mitochondria are shown to be crucial targets in alpha-tocopheryl
      succinate-induced caspase-dependent cell death in human carcinoma A431 cells.

PMID- 23150808
TI  - Gene Expression upon Proliferation and Differentiation of Hematopoietic Cells
      with Ph Chromosome ex vivo.
AB  - The genesp53, mdm2, p21, c-myc,bcr/abl, bcr, bcl2, bax, and gapdh participate in
      the regulation of cell proliferation and differentiation, apoptosis and cell
      distribution for the cell cycle ex vivo in the Ph(+)cells of chronic myeloid
      leukemia containing the Ph chromosome andbcr/abloncogene. Expression of these
      genes correlates with regulation of cell proliferation and differentiation by
      alternating proliferation and maturation stages for three main Ph+cell types that
      occur under chronic myeloid leukemia. Thep53, p21, mdm2, and gapdh genes
      overexpress in active proliferating myeloid cells in the cell cycle S+ G2/M
      phases and when the phases are coincident with the proliferation stage.
      Expression of these genes decreases to a considerable level under alternation of
      the Ph(+)cell proliferation and maturation stages and whenever the expression is
      greatly diminished under significant neutrophil accumulation and especially under
      repeated alternation of the stages. In the course of neutrophil maturation, gene
      expression levels decrease in the range of gapdh > actin > c-myc, bcr/abl,p21 >
      p53 > bcl2 > bax.The expression levels of these genes in neutrophils are lower
      than those in myelocytes and lower by an order of magnitude than that in the
      cells with a prolonged proliferation stage. TheBcr/ablexpression gene under
      prolonged maturation and neutrophil accumulation is inhibited; however it is
      enhanced by 2-3 times for the proliferation stage with myelocyte accumulation.
      Minimalbcr/ablexpression is observed under overexpression ofp53, mdm2, p21, c
      myc,as well as under cell maximum at the S and G2/M phases. Bcr/abloverexpression
      is observed under low expression of thep53, p21, mdm2genes. In the Ph(+ )cells
      with a high P/D efficiency index (5-20), overexpression of the genes in the range
      ofbcr> gapdh>bcr/abl, as well as a decreased expression of thep53, bcl2, mdm2,
      p21<< gapdh genes is observed for Ph(+)cells from the CML blast crisis and CML
      acceleration phase. Low control of cell proliferation and cell cycle by gene
      regulators presumably promotesbcr/abloverexpression and activates the production
      ofbcr/abl+ cells. Apoptosis in the Ph(+ )cells is induced by expression of thebax
      > bcl2, r53, p21, c-myc andgapdhgenes. The blocking of Ph(+)cell apoptosis,
      neutrophil accumulation, and decrease in the expression of the p53, mdm2 and p21,
      c-myc,bcr/abl genes occur at the maturation stage.

PMID- 23150809
TI  - Dioxaphosphorinane-constrained nucleic Acid dinucleotides as tools for structural
      tuning of nucleic acids.
AB  - We describe a rational approach devoted to modulate the sugar-phosphate backbone
      geometry of nucleic acids. Constraints were generated by connecting one oxygen of
      the phosphate group to a carbon of the sugar moiety. The so-called
      dioxaphosphorinane rings were introduced at key positions along the sugar
      phosphate backbone allowing the control of the six-torsion angles alpha to zeta
      defining the polymer structure. The syntheses of all the members of the D-CNA
      family are described, and we emphasize the effect on secondary structure
      stabilization of a couple of diastereoisomers of alpha,beta-D-CNA exhibiting
      wether B-type canonical values or not.

PMID- 23150811
TI  - Screening tests of reproductive immunology in systemic lupus erythematosus.
AB  - Female patients in reproductive age with systemic lupus erythematosus and
      fertility complications together are observed by rheumatologists, gynecologists,
      and reproductive immunologists. The paper notes the presence of autoantibodies to
      zona pellucida, to phospholipids (phosphatidyl serine, phosphatidyl ethanolamine,
      phosphatidyl inositol, phosphatidyl glycerol, phosphatidic acid, annexin V, beta
      2 glycoprotein I, and cardiolipin) and of isoantibodies to sperm cells.
      Isoantibodies to sperm cells are not significantly predominant, but autoimmunity
      is well expressed in IgG positivity against phosphatidyl inositol, phosphatidyl
      ethanolamine, phosphatidyl serine, cardiolipin, and beta-2 glycoprotein I, as
      well as antizona pellucida antibodies in IgG isotype. According to the levels of
      autoantibodies we have to choose preventive treatment to protect mother and her
      foetus.

PMID- 23150812
TI  - Impact of ramadan intermittent fasting on oxidative stress measured by urinary 15
      f(2t)-isoprostane.
AB  - Fasting and caloric restriction have been associated with reduced incidence of
      chronic diseases and cancers. These effects have been attributed to reduced
      oxidative stress. Since Ramadan intermittent fasting (RIF) has been associated
      with reduced caloric intake, it was hypothesized that RIF would alleviate
      oxidative stress in healthy volunteers. The study was designed to elucidate the
      impact of RIF on oxidative stress measured by 15-F(2t)-Isoprostane (15FIP). Fifty
      healthy subjects (23 men and 27 women) who intended to fast Ramadan were
      recruited. Urine and serum sampling and anthropometric and dietary assessments
      were conducted one week before Ramadan (T0), at the end of the third week of
      Ramadan (T1), and one month after Ramadan (T2). Biochemical measurements included
      urinary 15FIP, creatinine, and hematological indices. Results revealed that the
      urinary level of 15FIP measured at T0 was normal, while they showed a
      significantly (P < 0.05) higher level when measured at T1 concomitant with a
      significant (P < 0.05) increase in the body weight and total body fat percent. In
      conclusion, results suggest that increased body weight is associated with
      increased lipid peroxidation and oxidative stress, and the impact of RIF on
      oxidative stress is mediated by the changes in body weight at the end of the
      month.

PMID- 23150813
TI  - Relationship between Plasma Ferritin Level and Siderocyte Number in
      Splenectomized beta-Thalassemia/HbE Patients.
AB  - Introduction. In iron overload status, excess iron deposits in
      reticuloendothelial cells and tissues and can be detected using Prussian blue
      staining. The aim of this paper was to investigate the relationship between
      siderocyte numbers and plasma ferritin levels (a practically standard marker of
      iron overload) in the blood of the splenectomized and nonsplenectomized beta
      thalassemia/HbE patients, who are at risk of iron overload. Methods. EDTA blood
      samples from 64 patients with 35 splenectomized and 29 nonsplenectomized beta
      thalassemia/HbE patients, who received regular blood transfusions, and 20 normal
      individuals were investigated for siderocyte numbers, plasma ferritin levels, and
      complete blood counts. Results. The average percent siderocytes in splenectomized
      and nonsplenectomized beta-thalassemia/HbE patients were 11.5% and 0.08%,
      respectively, and plasma ferritin levels of 2,332 MUg/L and 1,279 MUg/L,
      respectively. Percent siderocytes showed a good correlation with plasma ferritin
      levels only in splenectomized patients (r = 0.69, P < 0.001). A receiver
      operating curve analysis from splenectomized patients' data indicated that
      siderocytes at 3% cut-off are the best predictor for plasma ferritin level
      >=1,000 MUg/L with 92.9% sensitivity and 42.9% specificity. Conclusion.
      Circulating siderocyte numbers can be used as a screening test for the assessment
      of the iron overload in splenectomized beta-thalassemia/HbE patients in the place
      where serum ferritin is not available.

PMID- 23150810
TI  - Challenges and opportunities for small molecule aptamer development.
AB  - Aptamers are single-stranded oligonucleotides that bind to targets with high
      affinity and selectivity. Their use as molecular recognition elements has emerged
      as a viable approach for biosensing, diagnostics, and therapeutics. Despite this
      potential, relatively few aptamers exist that bind to small molecules. Small
      molecules are important targets for investigation due to their diverse biological
      functions as well as their clinical and commercial uses. Novel, effective
      molecular recognition probes for these compounds are therefore of great interest.
      This paper will highlight the technical challenges of aptamer development for
      small molecule targets, as well as the opportunities that exist for their
      application in biosensing and chemical biology.

PMID- 23150814
TI  - Phylogenetic analysis of hepatitis e virus in northwest India.
AB  - Genotyping and subtyping are important to understand epidemiology of the
      hepatitis E virus so as to improve control measures to prevent transmission of
      virus in the community. Hence, the aim of the current study was to identify the
      prevalent HEV genotypes in Rajasthan in acute sporadic hepatitis E cases with
      varying degree of liver failure. We studied hepatitis E virus (HEV) isolates from
      hospitalized patients in Rajasthan, western India. In a total of seventeen HEV
      sequences, six acute viral hepatitis, seven acute liver failure, and 4 acute- on
      chronic cases were analyzed. Subtypes 1a and 1c of HEV are prevalent in Northwest
      India.

PMID- 23150815
TI  - Factors Affecting Acceptance and Intention to Receive Pandemic Influenza A H1N1
      Vaccine among Primary School Children: A Cross-Sectional Study in Birmingham, UK.
AB  - UK pandemic influenza strategy focused on vaccination of high risk groups,
      although evidence shows that school-age children have the highest infection
      rates. Vaccination of children might be an additional strategy. We undertook a
      cross-sectional study amongst 149 parents of primary school children aged 4-7
      years in Birmingham, UK to quantify intention to accept pandemic influenza
      vaccine and identify factors affecting uptake. Ninety-one (61.1%, 95% CI 52.8,
      68.9) had or would accept vaccine for their child. The most common reasons for
      declining vaccine were concerns about safety (58.6% reported this), side effects
      (55.2%), or believing their child had already had swine flu (12.1%). Parents of
      nonwhite ethnicity (OR 2.4 (1.1, 5.0)) and with asthmatic children (OR 6.6 (1.4,
      32.1)) were significantly more likely to accept pandemic vaccine, as were those
      whose children had ever received seasonal vaccine and those who believed swine
      flu to be a serious threat (OR 4.2 (1.9, 9.1)). Parents would be more likely to
      accept vaccination if they received a letter of invite, if the government
      strongly encouraged them, if it were administered at school, and if it were more
      thoroughly tested. Accurate media portrayal of safety of the vaccine during
      future pandemics will be essential.

PMID- 23150816
TI  - Effectiveness of international surgical program model to build local
      sustainability.
AB  - Background. Humanitarian medical missions may be an effective way to temporarily
      overcome limitations and promote long-term solutions in the local health care
      system. Operation Smile, an international medical not-for-profit organization
      that provides surgery for patients with cleft lip and palate, not only provides
      surgery through short-term international missions but also focuses on developing
      local capacity. Methods. The history of Operation Smile was evaluated globally,
      and then on a local level in 3 countries: Colombia, Bolivia, and Ethiopia.
      Historical data was assessed by two-pronged success of (1) treating the surgical
      need presented by cleft patients and (2) advancing the local capacity to provide
      primary and ongoing care to patients. Results. The number of patients treated by
      Operation Smile has continually increased. Though it began by using only
      international teams to provide care, by 2012, this had shifted to 33% of patients
      being treated by international teams, while the other 67% received treatment from
      local models of care. The highest level of sustainability was achieved in
      Columbia, where two permanent centers have been established, followed by Bolivia
      and lastly Ethiopia. Conclusions. International missions have value because of
      the patients that receive surgery and the local sustainable models of care that
      they promote.

PMID- 23150818
TI  - Thrombosis and aspirin: clinical aspect, aspirin in cardiology, aspirin in
      neurology, and pharmacology of aspirin.

PMID- 23150817
TI  - A comparative study of facial asymmetry in philippine, colombian, and ethiopian
      families with nonsyndromic cleft lip palate.
AB  - Objective. To compare the asymmetry displayed by Philippine, Colombian, and
      Ethiopian unaffected parents of patients with nonsyndromic cleft palate (NSCLP)
      and a control population. Methods. Facial measurements were compared between
      unaffected parents of NSCLP patients and those in the control group for three
      populations from South America, Asia, and Africa by anthropometric and
      photographic measurements. Fluctuating and directional asymmetries, height and
      width proportions, were analyzed and compared. Results. Fluctuating asymmetries
      (ear length, middle line to Zigion perpendicular for left and right sides) and
      variations in the facial thirds demonstrated statistical significance in the
      study group of unaffected parents from Colombia and Philippines, while increased
      interorbital distance was evident in the unaffected Ethiopian parents of NSCLP
      patients. Conclusions. The facial differences in unaffected parents could
      indicate an underlying genetic liability. Identification of these differences has
      relevance in the understanding of the etiology of NSCLP.

PMID- 23150819
TI  - Pain narratives in breast cancer survivors.
AB  - In-depth interviews were conducted with French breast cancer survivors 24 month
      after cancer diagnosis (N = 21 women). We documented their experience of chronic
      pain, compared their pain narratives with their answers to the WHOQOL-BREF
      questionnaire, and studied both the meaning they gave to their pain and how they
      dealt with it in their daily lives. Half of participants reported are suffering
      from iatrogenic chronic pain. Most of the time, this pain was not captured by the
      WHOQOL questionnaire and was not medically treated. Patients "normalized" their
      pain in various ways: they considered it either as a necessary step on the road
      to recovery, as the proof of treatment efficacy, or as a permanent condition one
      must learn to live with. They learned to deal with pain by taking precautions,
      giving up certain activities, and changing the way they performed others.
      Participants were also prone to compare themselves with other patients suffering
      worse pain. Breast cancer survivors should be better informed about chronic pain
      and how to alleviate it. Physicians should contribute to fighting pain-related
      beliefs which lead patients to conceal their pain. Techniques used by patients to
      cope with chronic pain in their daily lives should also be promoted.

PMID- 23150820
TI  - Pain management in laparoscopic donor nephrectomy: a review.
AB  - The management of postoperative pain is a key to patient early recovery, in
      particular, where the surgery was performed to benefit another human being. In
      recent years it has been recognized that multimodal analgesic methods are
      superior for postoperative pain relief. It is also imperative to remember that
      inadequately managed acute postoperative pain opens the doorway to possible
      suffering from chronic postoperative pain later. Although the laparoscopic donor
      nephrectomy has reduced the disincentives associated with open surgery, still
      significant percentage of donors suffers from postoperative pain. In the UK,
      patient-controlled analgesic system (PCAS) using morphine for postoperative pain
      relief is being used in majority of the transplant centres. Though opioids
      provide good analgesia, they are far from being an ideal analgesic due to their
      adverse effects. This paper pragmatically looks in depth on different modalities
      of pain management in patients undergoing laparoscopic live donor nephrectomy.

PMID- 23150821
TI  - Lung compliance and chronic obstructive pulmonary disease.
AB  - Chronic obstructive pulmonary disease, namely, pulmonary emphysema and chronic
      bronchitis, is a chronic inflammatory response of the airways to noxious
      particles or gases, with resulting pathological and pathophysiological changes in
      the lung. The main pathophysiological aspects of the disease are airflow
      obstruction and hyperinflation. The mechanical properties of the respiratory
      system and its component parts are studied by determining the corresponding
      volume-pressure (P-V) relationships. The consequences of the inflammatory
      response on the lung structure and function are depicted on the volume-pressure
      relationships.

PMID- 23150822
TI  - Stereotactic body radiotherapy for metachronous multisite oligo-recurrence: a
      long-surviving case with sequential oligo-recurrence in four different organs
      treated using locally radical radiotherapy and a review of the literature.
AB  - Stereotactic body radiotherapy (SBRT) for oligometastases represents a recent
      trend in radiation oncology. While abundant data are available regarding the use
      of SBRT for the treatment of lung or liver oligometastases from various
      retrospective series and prospective trials, relatively little information has
      been accumulated for the treatment of oligometastases at sites other than the
      lungs and liver, particularly for sequential oligometastases in multiple organs.
      Oligometastases with primary lesions controlled is called "oligo-recurrence." We
      describe herein the case of a lung cancer patient who developed repeated oligo
      recurrence at multiple sites that were each controlled by radical radiotherapy
      and achieved long-term survival and discuss the merits of locally aggressive
      radiotherapy for this type of disease condition with reviewing the literature.
      Although further investigation should be undertaken to clarify the benefits,
      objectives, and methods of SBRT for the treatment of oligometastases, we believe
      utilization of SBRT may be worthwhile for patients with remote metastases who
      hope for treatment to acquire better local control and possible longer survival.

PMID- 23150823
TI  - White Matter Atrophy in Patients with Mesial Temporal Lobe Epilepsy: Voxel-Based
      Morphometry Analysis of T1- and T2-Weighted MR Images.
AB  - Introduction. Mesial temporal lobe epilepsy (MTLE) associated with hippocampal
      sclerosis is highly refractory to clinical treatment. MRI voxel-based morphometry
      (VBM) of T1-weighted images has revealed a widespread pattern of gray matter (GM)
      and white matter (WM) atrophy in MTLE. Few studies have investigated the role of
      T2-weighted images in revealing WM atrophy using VBM. Objectives. To compare the
      results of WM atrophy between T1- and T2-weighted images through VBM. Methods. We
      selected 28 patients with left and 27 with right MTLE and 60 normal controls. We
      analyzed T1- and T2- weighted images with SPM8, using VBM/DARTEL algorithm to
      extract maps of GM and WM. The second level of SPM was used to investigate areas
      of WM atrophy among groups. Results. Both acquisitions showed bilateral
      widespread WM atrophy. T1-weighted images showed higher sensibility to detect
      areas of WM atrophy in both groups of MTLE. T2-weighted images also showed areas
      of WM atrophy in a more restricted pattern, but still bilateral and with a large
      area of superposition with T1-weighted images. Conclusions. In MTLE, T1-weighted
      images are more sensitive to detect subtle WM abnormalities using VBM, compared
      to T2 images, although both present a good superposition of statistical maps.

PMID- 23150824
TI  - Rheumatoid arthritis and primary biliary cirrhosis: cause, consequence, or
      coincidence?
AB  - Primary biliary cirrhosis (PBC) is a progressive cholestatic liver disease
      characterized serologically by cholestasis and the presence of high-titre
      antimitochondrial antibodies and histologically by chronic nonsuppurative
      cholangitis and granulomata. PBC patients often have concomitant autoimmune
      diseases, including arthropathies. This raises the question as to whether there
      are shared features in the pathogenesis of those diseases with the pathogenesis
      of PBC. Epidemiological and large case studies have indicated that although the
      incidence of rheumatoid arthritis (RA) is not significantly raised in PBC
      patients, there appears to be a higher rate of RA in PBC patients and their
      relatives. Genetic studies have demonstrated that several genes implicated in PBC
      have also been implicated in RA. Epigenetic studies provided a wealth of data
      regarding RA, but the findings on epigenetic changes in PBC are very limited. As
      well, certain infectious agents identified in the pathogenesis of PBC may also
      play a role in the pathogenesis of RA. These data suggest that although RA is not
      significantly present in PBC, some individuals with certain genetic traits and
      environmental exposures may develop both conditions. This concept may also apply
      to other concomitant diseases found in PBC patients.

PMID- 23150825
TI  - The use of epidermal growth factor receptor monoclonal antibodies in squamous
      cell carcinoma of the head and neck.
AB  - Targeting of the EGF receptor (EGFR) has become a standard of care in several
      tumor types. In squamous cell carcinoma of the head and neck, monoclonal
      antibodies directed against EGFR have become a regular component of therapy for
      curative as well as palliative treatment strategies. These agents have anti-tumor
      efficacy as a single modality and have demonstrated synergistic tumor killing
      when combined with radiation and/or chemotherapy. While cetuximab has been the
      primary anti-EGFR monoclonal antibody used in the US, variant anti-EGFR
      monoclonal antibodies have been used in several clinical studies and shown
      benefit with improved toxicity profiles. Next generation anti-EGFR monoclonal
      antibodies may demonstrate multi-target epitope recognition, enhanced immune cell
      stimulation, or conjugation with radioisotopes in order to improve clinical
      outcomes. Identification of the specific patient subset that would optimally
      benefit from anti-EGFR monoclonal antibodies remains an elusive goal.

PMID- 23150826
TI  - Host-pathogen interactions of retroviruses.

PMID- 23150827
TI  - The Presence of Anti-HLA Antibodies before and after Allogeneic Hematopoietic
      Stem Cells Transplantation from HLA-Mismatched Unrelated Donors.
AB  - Although anti-human leukocyte antigen antibodies (anti-HLA Abs) are important
      factors responsible for graft rejection in solid organ transplantation and play a
      role in post-transfusion complications, their role in allogeneic hematopoietic
      stem cell transplantation (allo-HSCT) has not been finally defined. Enormous
      polymorphism of HLA-genes, their immunogenicity and heterogeneity of antibodies,
      as well as the growing number of allo-HSCTs from partially HLA-mismatched donors,
      increase the probability that anti-HLA antibodies could be important factors
      responsible for the treatment outcomes. We have examined the incidence of anti
      HLA antibodies in a group of 30 allo-HSCT recipients from HLA-mismatched
      unrelated donors. Anti-HLA Abs were identified in sera collected before and after
      allo-HSCT. We have used automated DynaChip assay utilizing microchips bearing
      purified class I and II HLA antigens for detection of anti-HLA Abs. We have
      detected anit-HLA antibodies against HLA-A, B, C, DR, DQ and DP, but no donor or
      recipient-specific anti-HLA Abs were detected in the studied group. The
      preliminary results indicate that anti-HLA antibodies are present before and
      after allo-HSCT in HLA-mismatched recipients.

PMID- 23150828
TI  - The role of large-format histopathology in assessing subgross morphological
      prognostic parameters: a single institution report of 1000 consecutive breast
      cancer cases.
AB  - Breast cancer subgross morphological parameters (disease extent, lesion
      distribution, and tumor size) provide significant prognostic information and
      guide therapeutic decisions. Modern multimodality radiological imaging can
      determine these parameters with increasing accuracy in most patients. Large
      format histopathology preserves the spatial relationship of the tumor components
      and their relationship to the resection margins and has clear advantages over
      traditional routine pathology techniques. We report a series of 1000 consecutive
      breast cancer cases worked up with large-format histology with detailed
      radiological-pathological correlation. We confirmed that breast carcinomas often
      exhibit complex subgross morphology in both early and advanced stages. Half of
      the cases were extensive tumors and occupied a tissue space >=40 mm in its
      largest dimension. Because both in situ and invasive tumor components may exhibit
      unifocal, multifocal, and diffuse lesion distribution, 17 different breast cancer
      growth patterns can be observed. Combining in situ and invasive tumor components,
      most cases fall into three aggregate growth patterns: unifocal (36%), multifocal
      (35%), and diffuse (28%). Large-format histology categories of tumor size and
      disease extent were concordant with radiological measurements in approximately
      80% of the cases. Noncalcified, low-grade in situ foci, and invasive tumor foci
      <5 mm were the most frequent causes of discrepant findings.

PMID- 23150829
TI  - Hepatocytes polyploidization and cell cycle control in liver physiopathology.
AB  - Most cells in mammalian tissues usually contain a diploid complement of
      chromosomes. However, numerous studies have demonstrated a major role of "diploid
      polyploid conversion" during physiopathological processes in several tissues. In
      the liver parenchyma, progressive polyploidization of hepatocytes takes place
      during postnatal growth. Indeed, at the suckling-weaning transition, cytokinesis
      failure events induce the genesis of binucleated tetraploid liver cells. Insulin
      signalling, through regulation of the PI3K/Akt signalling pathway, is essential
      in the establishment of liver tetraploidization by controlling cytoskeletal
      organisation and consequently mitosis progression. Liver cell polyploidy is
      generally considered to indicate terminal differentiation and senescence, and
      both lead to a progressive loss of cell pluripotency associated to a markedly
      decreased replication capacity. Although adult liver is a quiescent organ, it
      retains a capacity to proliferate and to modulate its ploidy in response to
      various stimuli or aggression (partial hepatectomy, metabolic overload (i.e.,
      high copper and iron hepatic levels), oxidative stress, toxic insult, and chronic
      hepatitis etc.). Here we review the mechanisms and functional consequences of
      hepatocytes polyploidization during normal and pathological liver growth.

PMID- 23150830
TI  - Antimicrobial or subantimicrobial antibiotic therapy as an adjunct to the
      nonsurgical periodontal treatment: a meta-analysis.
AB  - The use of antibiotics in nonsurgical periodontal treatment is indicated in cases
      in which scaling and root planing present important limitations. However, their
      use is controversial due to the secondary effects associated with them and the
      disagreements regarding their prescription. The aim of this study is to determine
      the effectiveness of systemic antibiotics in the management of aggressive and
      chronic periodontitis. The study was based on a search of randomized, controlled
      clinical trials. Common data were concentrated and evaluated by means of an
      analysis of variance (ANOVA), and a meta-analysis of the results was performed.
      The meta-analysis (P < 0.05, 95% confidence interval, post hoc Bonferroni)
      determined that the supplementation of nonsurgical periodontal therapy with a
      systemic antibiotic treatment-amoxicillin with clavulanic acid and metronidazole
      or subantimicrobial dose doxycycline-provides statistically significant results
      in patients with aggressive or chronic periodontitis under periodontal treatment,
      whilst increasing the clinical attachment level of the gingiva and reducing
      periodontal probing depth.

PMID- 23150831
TI  - Critical analysis of esophageal multichannel intraluminal impedance monitoring 20
      years later.
AB  - Multichannel intraluminal impedance (MII) for the evaluation of esophageal
      diseases was created in 1991 trying to solve previous limitations of esophageal
      function test. MII-pH is able to determine the physical characteristics of the
      refluxate (liquid, gas, or mixed) and nonacidic GER. MII-manometry can determine
      the presence of bolus and its relation with peristalsis. This paper makes a
      critical analysis of the clinical applications of MII 20 years after its
      creation. Literature review shows that MII made great contributions for the
      understanding of esophageal physiology; however, direct clinical applications are
      few. MII-pH was expected to identify patients with normal acid reflux and
      abnormal nonacidic reflux. These patients are rarely found off therapy, that is,
      nonacidic reflux parallels acid reflux. Furthermore, the significance of isolated
      nonacidic reflux is unclear. Contradictory MII-manometry and conventional
      manometry findings lack better understanding and clinical implication as well as
      the real significance of bolus transit.

PMID- 23150832
TI  - Evaluation of X-Chromosome Inactivation Patterns in Patients with Acute Myeloid
      Leukemia during Remission.
AB  - The aim of this study was to evaluate the patterns of X-chromosome inactivation
      during the remission in acute myeloid leukemia (AML) at the RNA level. Two
      hundred normal females and 45 female patients with AML entered the study. The
      frequency of heterozygosity was 48.5% (119/245) for P55, 40% (93/245) for IDS,
      and only 28.9% (71/245) for G6PD. Some individuals were heterozygous for more
      than one gene polymorphism. Overall, one hundred normal individuals proved showed
      to be heterozygous for at least one of the above polymorphisms. 92/100 (92%)
      normal females showed a polyclonal pattern. Clonal patterns were observed in
      44/45 (98%) AML patients at presentation. Of 27 patients who were followed after
      remission, 23 (85.2%) patients showed a clonal pattern. Ten patients were
      available for a longer followup (up to 12 months) and the clonal pattern was
      observed in seven patients. It can be concluded that clonality at remission is a
      frequent event in AML and does not necessarily mean relapse of the disease. There
      is also a possibility of conversion of clonality to polyclonality over time.

PMID- 23150833
TI  - The association of hypovitaminosis d with the metabolic syndrome is independent
      of the degree of obesity.
AB  - Background. It remains uncertain whether the metabolic syndrome (MS) or insulin
      resistance contribute to the association between vitamin D deficiency and
      obesity. Methods. We conducted a cross-sectional survey of 343 subjects who were
      overweight or obese. We analyzed anthropometric data and the presence or absence
      of MS. Additionally, we determined 25-hydroxyvitamin D (25OHD) and insulin
      concentrations, and the HOMA index was calculated. Chi-square test,Mann-Whitney U
      test, Student's t-tests,and logistic regression analysis were used. Results. The
      mean age of the patients was 42 +/- 11 years, and 65.9% were women. The mean BMI
      was 34.7 +/- 8.3 kg/m(2) and 25(OH)D levels were 53.7 +/- 29.8 nmol/L. Forty-six
      patients (13.4%) had MS. Vitamin D status was associated with the degree of
      obesity, especially with a BMI > 40 kg/m(2). Patients with MS had lower levels of
      25(OH)D than patients without (43.3 +/- 29.0 versus 55.3 +/- 29.6 mmol/L, resp.),
      and the odds ratio for hypovitaminosis D was 2.7 (confidence interval (CI), 1.14
      6.4) (P = .023) for patients with MS versus patients without MS, irrespective of
      the degree of obesity. Conclusions. Our data confirm the association between
      vitamin D and MS and suggest that this association is independent of the degree
      of obesity.

PMID- 23150834
TI  - Therapeutic role of mobilized bone marrow cells in children with nonischemic
      dilated cardiomyopathy.
AB  - Dilated cardiomyopathy is an important cause of congestive cardiac failure in
      infants and children. Mobilizing hematopoietic progenitor cells is a promising
      intervention to this deadly disease. Aim. Evaluate granulocyte colony stimulating
      factor (GCSF) as therapeutic modality in children with idiopathic dilated
      cardiomyopathy (IDCM). Subjects and Methods. This case-control prospective study
      was conducted on 20 children with IDCM following up at Cardiology Clinic
      Children's Hospital, Ain Shams University (group 1) who were compared to another
      10 age-, sex-, duration-of-illness-, and systolic-function-matched children with
      IDCM as control (group 2). They were subjected to history taking, clinical
      examination, echocardiography, and peripheral blood CD34+ cell assessment before
      and one week after GCSF intake for 5 consecutive days (by group 1 but not group
      2). Results. A significant improvement in echocardiographic data and CD34+-T-cell
      increase was found in group 1 one week after GCSF intake and for the next 6
      months CD34+ T cells percentage of change showed no significant correlation with
      the that of the left ventricular dimensions and systolic function. Conclusion.
      Administration of GCSF to children with IDCM resulted in clinical and
      echocardiographic improvement not correlated to mobilized CD34+ T cells, implying
      involvement of additional mechanisms over simple stem cell mobilization.

PMID- 23150835
TI  - Guided self-help for prevention of depression and anxiety in women with breast
      cancer.
AB  - Depression and anxiety are prevalent in women with breast cancer. We developed a
      self-help kit as a self-learning package of necessary preparatory information
      (basic knowledge on chemotherapy, side effects, and problem-solving skills). We
      provided an oncology nurse-guided self-help kit with a cognitive behavioral
      therapy approach to 46 women with breast cancer in the intervention group and
      usual care to 36 in the control group in outpatient chemotherapy settings. The
      oncology nurse monitored and facilitated the patient's progress using the diary
      during the patient's chemotherapy. We also provided professional-led support
      group programs. Depression, anxiety, and quality of life were measured at
      baseline, 1 week, 3 months, and 6 months. The chi-square test and t were used to
      examine differences between the two groups, and repeated measures analysis of
      variance was used to test the effects of the intervention on the measures over
      time. All depression and anxiety scores were improved in both the intervention
      and control groups, but there were no significant differences between the two
      groups. Further studies are needed to evaluate the effectiveness of an oncology
      nurse-guided self-help approach for cancer patients.

PMID- 23150837
TI  - Isolated axillary lymph node metastasis from serous ovarian cancer.
AB  - A 68-year-old female with past medical history of stage IIIc serous ovarian
      cancer after cytoreductive surgery and adjuvant chemotherapy came to clinic for
      regular follow-up visit. Physical examination was completely normal except for an
      isolated left axillary lymph node enlargement. Patient's abdominal sonogram and
      CT scan of abdomen and pelvis did not show any other new metastasis. Surgical
      excisional biopsy of the lymph node was performed and pathology revealed features
      of metastatic serous ovarian carcinoma.

PMID- 23150838
TI  - Pelvic nephroureterectomy for renal cell carcinoma in an ectopic kidney.
AB  - We present a case of an ectopic renal tumor in a 61-year-old morbidly obese man
      with a pelvic kidney found after presenting with hematuria and irritative voiding
      symptoms. The mass, along with the ectopic kidney and ureter, was radically
      resected through an open operation that involved removing both them and the renal
      vessels from the underlying iliac vessels. Pathological analysis demonstrated an
      8.3 cm papillary renal cell carcinoma (RCC) with oncocytic features, Fuhrman
      nuclear grade 3, with angiolymphatic invasion and negative margins. The patient
      has been recurrence-free for over four years since tumor resection.

PMID- 23150839
TI  - Primary renal embryonal rhabdomyosarcoma in adults: a case report and review of
      the literature.
AB  - Adult renal rhabdomyosarcoma is a rare subtype of renal sarcoma. We present a
      case of a renal mass treated with radical nephrectomy that subsequently was shown
      to be renal rhabdomyosarcoma. We discuss the clinical presentation, imaging
      findings, and histology for this case and review the available literature.

PMID- 23150836
TI  - Effects of antipsychotics on dentate gyrus stem cell proliferation and survival
      in animal models: a critical update.
AB  - Schizophrenia is a complex psychiatric disorder. Although a number of different
      hypotheses have been developed to explain its aetiopathogenesis, we are far from
      understanding it. There is clinical and experimental evidence indicating that
      neurodevelopmental factors play a major role. Disturbances in neurodevelopment
      might result in alterations of neuroanatomy and neurochemistry, leading to the
      typical symptoms observed in schizophrenia. The present paper will critically
      address the neurodevelopmental models underlying schizophrenia by discussing the
      effects of typical and atypical antipsychotics in animal models. We will
      specifically discuss the vitamin D deficiency model, the poly I:C model, the
      ketamine model, and the postnatal ventral hippocampal lesion model, all of which
      reflect core neurodevelopmental issues underlying schizophrenia onset.

PMID- 23150840
TI  - Cholesterol granuloma of the frontal sinus: a case report.
AB  - Cholesterol granulomas are common in the mastoid antrum and air cells of the
      temporal bone. In the paranasal sinuses, especially in the frontal sinus, they
      have occasionally been mentioned in the literature. The pathogenesis is unknown,
      but the majority of the authors support the concept of airway obstruction in the
      cells well pneumatised of temporal bone and paranasal sinuses. The authors report
      a case of cholesterol granuloma of the frontal sinus treated with radical
      surgical techniques, and they also recommend an endoscopic approach to frontal
      sinus to restore or enlarge the nose-frontal canal and promote drainage and
      ventilation of the frontal sinus.

PMID- 23150841
TI  - Radiographically negative, asymptomatic, sentinel lymph node positive cutaneous T
      cell lymphoma in a 3-year-old male: a case report.
AB  - We present a case of a 3-year-old male originally diagnosed with a CD30+
      anaplastic cutaneous T-cell lymphoma with no evidence of systemic disease after
      CT scan, PET scan, and bone marrow aspiration. Sentinel lymph node biopsy (SLNB)
      was performed as an additional step in the workup and showed microscopic disease.
      Current management/recommendations for cutaneous T-cell lymphoma do not include
      SLNB. Medical and surgical management of cutaneous malignancies is dramatically
      different for local versus advanced disease. Therefore adequate evaluation is
      necessary to properly stage patients for specific treatment. Such distinction in
      extent of disease suggests more extensive therapy including locoregional
      radiation and systemic chemotherapy versus local excision only. Two international
      case reports have described SLNB in cutaneous T-cell lymphoma with one
      demonstrating evidence of node positive microscopic disease despite a negative
      metastatic disease workup. This case is being presented as a novel case in a
      child with implications including lymphoscintigraphy and SLNB as a routine
      procedure for evaluation and staging of cutaneous T-cell lymphoma if the patient
      does not demonstrate evidence of metastatic disease on routine workup.

PMID- 23150842
TI  - H1N1 Influenza Viral Infection in a Postpartum Young Woman Causes Respiratory
      Failure: What the Care Providers Ought to Know?
AB  - Pregnant and postpartum women are considered a population at increased risk of
      hospitalization of H1N1 infection. We report the case of a young postpartum
      woman, who developed evidence of respiratory failure reaching the point of
      requiring intubation due to an H1N1 influenza virus infection two days after a
      caesarean delivery. We emphasize the diagnosis, management, and the outcome
      focusing on the question "what the care providers, including obstetric health
      care workers, ought to know?" Diagnostic and management strategy for pregnant or
      postpartum women with novel influenza A (H1N1) viral infection and increased
      awareness amongst patients and health care professionals may result in improved
      survival.

PMID- 23150843
TI  - Clinical manifestations of aortocaval fistulas in ruptured abdominal aortic
      aneurysm: report of two cases.
AB  - Aortocaval fistula (ACF) is an unusual complication of ruptured abdominal aortic
      aneurysm (AAA), involving less than 3-6% of all ruptured cases. The clinical
      presentation is often obscure, depending on the coexistence of retroperitoneal
      rupture and hemodynamic instability. Prompt preoperative diagnosis is essential
      in order to plan the operative approach and improve patient's outcome. We report
      the surgical treatment of two patients presented in the emergency department with
      ACF due to ruptured AAA, each with different clinical presentation, emphasizing
      the high index of suspicion needed by the clinician to early diagnose and treat
      this often lethal condition. Operative strategy and special considerations in the
      management of this subgroup of patients are also discussed.

PMID- 23150844
TI  - Falls and fractures in the elderly with sinus node disease: the impact of
      pacemaker implantation.
AB  - Background. Falls and fractures in the elderly are among the leading causes of
      disability. We investigated whether pacemaker implantation prevents falls in
      patients with SND in a large cohort of patients. Methods. Patient demographics
      and medical history were collected prospectively. Fall history was
      retrospectively reconstituted from available medical records. The 10-year
      probability for major osteoporotic fractures was calculated retrospectively from
      available medical records using the Swiss fracture risk assessment tool FRAX
      Switzerland. Results. During a mean observation period of 2.3 years after
      implantation, the rates of fallers and injured fallers with fracture were reduced
      to 15% and 6%, respectively. This corresponds to a relative reduction in the
      number of fallers of 75% (P < 0.001) and of injured fallers of 63% (P = 0.014)
      after pacemaker implantation. Similarly, the number of falls was reduced from 60
      (48%) before pacemaker implantation to 22 (18%) thereafter (relative reduction
      63%, P = 0.035) and the number of falls with injury from 22 (18%) to 7 (6%),
      which corresponds to a relative reduction of 67%, P = 0.013. Conclusion. In
      patients with SND, pacemaker implantation significantly reduces the number of
      patients experiencing falls, the total number of falls, and the risk for
      osteoporotic fractures.

PMID- 23150845
TI  - Congratulations to the 2012 RSNA Outstanding Educator: Marilyn J. Goske, MD.

PMID- 23150846
TI  - Complications of aortic valve surgery: manifestations at CT and MR imaging.
AB  - Aortic valve replacement accounts for a significant portion of cardiac surgeries
      in the United States. Despite advances in prosthetic heart valve design, surgical
      technique, and postoperative care, complications after aortic valve replacement
      remain a leading cause of morbidity and mortality. Routine surveillance of
      prosthetic heart valves with transthoracic echocardiography (TTE),
      transesophageal echocardiography (TEE), and fluoroscopy is important, as these
      techniques allow accurate detection of prosthetic valve dysfunction. However,
      echocardiography and fluoroscopy may not allow identification of the specific
      underlying cause, including paravalvular leak, dehiscence, endocarditis,
      obstruction, structural failure, pseudoaneurysm formation, aortic dissection, and
      hemolysis. Magnetic resonance (MR) imaging and computed tomography (CT) have an
      emerging role as diagnostic tools complementary to conventional imaging for
      detection and monitoring of complications after aortic valve replacement. The
      choice between CT and MR imaging depends on individual patient characteristics,
      the type of prosthetic valve, and the acuity of the clinical situation. In
      general, screening with TTE followed by TEE is recommended. When results of TTE
      and TEE are inconclusive, cardiac CT and MR imaging should be considered. The
      choice between these imaging techniques depends on the presence of patient
      specific contraindications to CT or MR imaging.

PMID- 23150847
TI  - Multidetector CT angiography in evaluation of prosthetic heart valve dysfunction.
AB  - Prosthetic heart valves (PHVs) are commonly implanted to replace diseased native
      heart valves. PHV dysfunction is an infrequent but potentially life-threatening
      condition. In daily clinical practice, transthoracic and transesophageal
      echocardiography and fluoroscopy are the imaging modalities used for diagnostic
      evaluation of suspected PHV dysfunction. These modalities may not allow
      determination of the cause of PHV dysfunction, mostly because of acoustic
      shadowing. Multidetector computed tomographic (CT) angiography is a promising
      complementary technique for evaluation of PHVs, especially in patients with PHV
      obstruction and endocarditis. The CT image quality of PHVs mainly depends on
      their composition, with most causing only limited artifacts. Retrospectively
      electrocardiographically gated acquisition is advisable for PHV imaging because
      it enables dynamic leaflet evaluation and anatomic assessment in both systole and
      diastole. For accurate image interpretation, dedicated reconstruction in plane
      with and perpendicular to the PHV leaflets is mandatory. Besides PHV assessment,
      CT also provides information on the coronary arteries, the location and patency
      of bypass grafts, the dimensions of the aorta, and the distance between the
      sternum and right ventricle, information valuable for planning repeat surgery. To
      achieve the optimal diagnostic yield in PHV imaging, multidisciplinary
      cooperation between the departments of cardiology, cardiothoracic surgery, and
      radiology is crucial.

PMID- 23150848
TI  - Radiopaque jaw lesions: an approach to the differential diagnosis.
AB  - Radiopaque jaw lesions are frequently encountered at radiography and computed
      tomography, but they are usually underevaluated or underdescribed in radiology
      reports. A systematic approach to the evaluation of radiopaque jaw lesions is
      necessary to diagnose the lesion or at least provide a meaningful differential
      diagnosis. To evaluate a radiopaque jaw lesion, the first, most important step is
      to categorize the lesion according to its attenuation, its relationship to the
      teeth, and its location with respect to the tooth. These basic observations are
      essential to the evaluation of any type of jaw lesion. Once these observations
      have been made, it is easy to create a proper differential diagnosis. The
      presence of important characteristics, such as margination, a perilesional halo,
      bone expansion, and growth pattern, as well as whether the lesion is sclerotic,
      has ground-glass attenuation, or is mixed lytic and sclerotic, further narrows
      the differential diagnosis. It is important to note that some radiopaque jaw
      lesions may be entirely lucent early in their evolution. Awareness of the
      demographic distribution of these lesions and their associated clinical features,
      as well as the radiologic approach, is important to explore the "terra incognita"
      of radiopaque jaw lesions.

PMID- 23150849
TI  - Teeth: what radiologists should know.
AB  - Disease of the teeth and their support structures is common and frequently seen
      at imaging of the head and neck. Recognition of dental disease by the
      interpreting radiologist has the potential to alter the course of patient care,
      such as when periapical disease is identified as the cause of sinusitis or
      pericoronitis is identified as the cause of deep neck infection. Furthermore,
      incidental recognition of carious lesions in both children and adults who are
      undergoing CT for other reasons may alert the patient and care team of the need
      for a dental consultation. In fact, most of the images of dental and periodontal
      conditions that are used in this article were obtained from CT studies that were
      performed to investigate other problems. Familiarity with the imaging appearance
      of common dental conditions, such as hyperdontia and hypodontia, tooth trauma,
      periodontal disease, caries, periapical disease, odontogenic sinusitis, and deep
      neck infections, allows the radiologist to render a timely, confident, and
      specific diagnosis of dental abnormalities, even when such findings are
      unexpected.

PMID- 23150850
TI  - IgG4-related disease of the head and neck: CT and MR imaging manifestations.
AB  - Immunoglobulin G4 (IgG4)-related disease is a recently established systemic
      disease that commonly involves the head and neck, including the salivary glands,
      lacrimal glands, orbits, thyroid gland, lymph nodes, sinonasal cavities,
      pituitary gland, and larynx. Although the definitive diagnosis of IgG4-related
      disease requires histopathologic analysis, elevated serum IgG4 levels are helpful
      in making the diagnosis. Because of the proposed clinical diagnostic criteria for
      this disease, cross-sectional imaging modalities such as computed tomography (CT)
      and magnetic resonance (MR) imaging play an important diagnostic role. CT and MR
      imaging findings of IgG4-related disease are usually nonspecific. At CT, involved
      organs may demonstrate enlargement or decreased attenuation; at T2-weighted MR
      imaging, they may have relatively low signal intensity owing to their increased
      cellularity and amount of fibrosis. Some pathologic entities involving the head
      and neck are now considered to be part of the IgG4-related disease spectrum,
      including idiopathic orbital inflammatory syndrome (inflammatory pseudotumor),
      orbital lymphoid hyperplasia, Mikulicz disease, Kuttner tumor, Hashimoto
      thyroiditis, Riedel thyroiditis, and pituitary hypophysitis. Because involvement
      of multiple sites is common in IgG4-related disease, radiologists should be
      familiar with manifestations of this systemic process outside the head and neck,
      in organs such as the pancreas, bile ducts, gallbladder, kidneys,
      retroperitoneum, mesentery, lungs, gastrointestinal tract, and blood vessels.
      Moreover, IgG4-related disease usually demonstrates a dramatic response to
      corticosteroid therapy, and radiologists should be familiar with its clinical and
      imaging manifestations to avoid a delay in diagnosis or unnecessary invasive
      interventions.

PMID- 23150851
TI  - Diabetic musculoskeletal complications and their imaging mimics.
AB  - Diabetes mellitus is increasingly prevalent and results in various clinically
      important musculoskeletal disorders affecting the limbs, feet, and spine as well
      as in widely recognized end-organ complications such as neuropathy, nephropathy,
      and retinopathy. Diabetic muscle ischemia-a self-limited disorder-may be confused
      with infectious or inflammatory myositis, venous thrombosis, or compartment
      syndrome. The absence of fever and leukocytosis, combined with the presence of
      bilaterally distributed lesions in multiple and often noncontiguous muscles in
      the legs, including the thighs, is suggestive of ischemia; by contrast, the
      presence of well-defined intramuscular abscesses with rimlike enhancement favors
      a diagnosis of infectious pyomyositis. In the diabetic foot, an ulcer, sinus
      tract, or abscess with an adjacent region of abnormal signal intensity in bone
      marrow favors the diagnosis of pedal osteomyelitis over that of neuropathic
      arthropathy. Contrast material-enhanced magnetic resonance imaging is important
      when planning the treatment of foot infections in diabetic patients because it
      allows the differentiation of viable tissue from necrotic regions that require
      surgical debridement in addition to antibiotic therapy. Subtraction images are
      particularly useful for visualizing nonviable tissue. Dialysis-associated
      spondyloarthropathy characteristically occurs in diabetic patients with a long
      history of hemodialysis. Intervertebral disk space narrowing without T2 signal
      hyperintensity, extensive endplate erosions without endplate remodeling, and
      facet joint involvement are suggestive of spondyloarthropathy instead of
      infectious diskitis or degenerative disk disease. Although the clinical features
      of these conditions may overlap, knowledge of the patient's medical history,
      coupled with recognition of key imaging characteristics, allows the radiologist
      to make a prompt and correct diagnosis that leads to appropriate management.

PMID- 23150852
TI  - Practice corner: a perfect fit.

PMID- 23150853
TI  - LI-RADS: a case-based review of the new categorization of liver findings in
      patients with end-stage liver disease.
AB  - Hepatocellular carcinoma (HCC) is a global health problem, with the burden of
      disease expected to increase in the coming years. Patients who are at increased
      risk for developing HCC undergo routine imaging surveillance, and once a focal
      abnormality is detected, evaluation with multiphasic contrast material-enhanced
      computed tomography or magnetic resonance imaging is necessary for diagnosis and
      staging. Currently, findings at liver imaging are inconsistently interpreted and
      reported by most radiologists. The Liver Imaging-Reporting and Data System (LI
      RADS) is an initiative supported by the American College of Radiology that aims
      to reduce variability in lesion interpretation by standardizing report content
      and structure; improving communication with clinicians; and facilitating decision
      making (eg, for transplantation, ablative therapy, or chemotherapy), outcome
      monitoring, performance auditing, quality assurance, and research. Five
      categories that follow the diagnostic thought process are used to stratify
      individual observations according to the level of concern for HCC, with the most
      worrisome imaging features including a masslike configuration, arterial phase
      hyperenhancement, portal venous phase or later phase hypoenhancement, an increase
      of 10 mm or more in diameter within 1 year, and tumor within the lumen of a vein.
      LI-RADS continues to evolve and is expected to integrate a series of improvements
      in future versions that will positively affect the care of at-risk patients.

PMID- 23150854
TI  - Radiologic findings in cases of attempted suicide and other self-injurious
      behavior.
AB  - Suicide is one of the leading causes of death in multiple age groups. Therefore,
      it is important that radiologists be aware of this commonly encountered entity.
      Attempted suicide may take a variety of forms; those discussed by the authors
      include sharp force injury, immolation and inhalation, ingestion, hanging,
      firearm use, jumping from a height, and drowning. Certain radiologic findings are
      commonly seen in cases of attempted suicide and other self-injurious behaviors.
      In some cases, especially when the patient is unconscious or is unwilling to
      provide a history, it may not be apparent that suicide has been attempted until
      characteristic imaging findings are recognized. Correct identification of suicide
      attempts on the basis of such findings will ensure that these patients receive
      appropriate psychiatric treatment. When a suicide attempt is unsuccessful, it is
      important to be familiar with the complications that may contribute to delayed
      mortality and morbidity. The radiologist plays an integral role in the acute
      medical or surgical management of patients who have attempted suicide. In
      addition, imaging examinations may provide useful forensic information.

PMID- 23150855
TI  - AIRP best cases in radiologic-pathologic correlation: localized amyloidosis of
      the renal pelvis.

PMID- 23150856
TI  - Endometriosis of abdominal and pelvic wall scars: multimodality imaging findings,
      pathologic correlation, and radiologic mimics.
AB  - Implantation of an endometriotic lesion within a pelvic or abdominal wall scar is
      an uncommon but well-described condition that may be the underlying cause of
      acute or chronic recurrent abdominal or pelvic pain, especially after cesarean
      section. Radiologists may not consider scar endometriosis when it is encountered
      at cross-sectional imaging. Cesarean section scars are the most common site of
      extraovarian or extrauterine endometriosis. The condition also has been
      identified in other uterine surgery-related scars and in the skin, subcutaneous
      tissues, and abdominal and pelvic wall musculature adjacent to these scars. The
      most plausible cause of scar endometriosis is implantation of endometrial stem
      cells at the surgical site at the time of uterine surgery. Patients with scar
      endometriosis may be asymptomatic or present with cyclical pain corresponding to
      the menstrual cycle. Cross-sectional imaging findings vary from the nonspecific
      to those suggestive of the diagnosis when combined with clinical history. In
      particular, the presence of blood products in an anterior abdominal wall mass at
      magnetic resonance (MR) imaging with no other explanation is strongly suggestive
      of scar endometriosis. Ultrasonography, computed tomography, and MR imaging may
      be used to depict an endometriotic lesion, exclude endometriosis, or provide
      evidence for an alternative diagnosis.

PMID- 23150857
TI  - AIRP best cases in radiologic-pathologic correlation: coal workers'
      pneumoconiosis.

PMID- 23150858
TI  - Alveolar echinococcosis: spectrum of findings at cross-sectional imaging.
AB  - Alveolar echinococcosis is a rare parasitic disease caused by the fox tapeworm
      Echinococcus multilocularis, which is endemic in many parts of the world. Without
      timely diagnosis and therapy, the prognosis is dismal, with death the eventual
      outcome in most cases. Diagnosis is usually based on findings at radiologic
      imaging and in serologic analyses. Because echinococcal lesions can occur almost
      anywhere in the body, familiarity with the spectrum of cross-sectional imaging
      appearances is advantageous. Echinococcal lesions may produce widely varied
      imaging appearances depending on the parasite's growth stage, the tissues or
      organs affected, and the presence of associated complications. Although the liver
      is the initial site of mass infestation by E multilocularis, the parasite may
      disseminate from there to other organs and tissues, such as the lung, heart,
      brain, bones, and ligaments. In severe infestations, the walls of the bile ducts
      and blood vessels may be invaded. Disseminated parasitic lesions in unusual
      locations with atypical imaging appearances may make it difficult to narrow the
      differential diagnosis. Ultrasonography, computed tomography (CT), magnetic
      resonance (MR) imaging with standard and diffusion-weighted sequences, and MR
      cholangiopancreatography all provide useful information and play complementary
      roles in detecting and characterizing echinococcal lesions. Cross-sectional
      imaging is crucial for differentiating echinococcosis from malignant processes:
      CT is most useful for depicting the peripheral calcifications surrounding
      established echinococcal cysts, and MR imaging is most helpful for identifying
      echinococcosis of the central nervous system.

PMID- 23150859
TI  - From the radiologic pathology archives: precocious puberty: radiologic-pathologic
      correlation.
AB  - Precocious puberty represents a unique diagnostic problem in which imaging plays
      an important role. Development of secondary sex characteristics may result from
      inappropriate activation of the hypothalamic-pituitary axis with release of
      gonadotropin, or from gonadotropin-independent secretion of sex steroids by the
      adrenal glands or gonads. A variety of lesions can manifest with precocious
      puberty, including various central nervous system (CNS) lesions, adrenal lesions,
      and sex cord-stromal tumors of the testis or ovary. CNS lesions causing
      precocious puberty are much more common in boys than in girls and are well
      evaluated with brain magnetic resonance imaging. Neoplastic (hypothalamic
      chiasmatic astrocytoma, suprasellar germinoma) and nonneoplastic (hypothalamic
      hamartoma, hydrocephalus, trauma, empty sella, infection, congenital midline
      anomalies) conditions may affect the function of the hypothalamic-pituitary axis.
      The adrenal cortex may produce sex hormones. Some adrenal cortical neoplasms
      (ACNs) in patients under 5 years of age are related to a mutation of the tumor
      suppressor gene p53 and represent a disease that is distinct from ACNs in older
      children and adults. Adrenal cortical hyperplasia secondary to an enzymatic
      defect in steroid biosynthesis causes virilization and salt wasting, which
      usually manifest in the neonatal period; however, milder forms of the disease may
      manifest in childhood. Female precocious puberty may be caused by an autonomously
      functioning ovarian cyst or a juvenile granulosa cell tumor of the ovary. Male
      precocious puberty may be caused by a sex steroid-producing Leydig or Sertoli
      cell tumor of the testis. Ultrasonography is the primary modality for evaluating
      the sex organs and may also be used to evaluate for adrenal abnormalities.

PMID- 23150860
TI  - Craniospinal abnormalities and neurologic complications of osteogenesis
      imperfecta: imaging overview.
AB  - Osteogenesis imperfecta is a rare genetic disorder that leads to progressive
      skeletal deformities due to deficits in type I collagen, the main
      pathophysiologic effect of the disease. In addition, it may lead to a wide range
      of associated neurologic abnormalities: The central nervous system is usually
      involved because of softening of bone at the base of the skull, with resultant
      upward migration of the upper cervical spine and odontoid process into the skull
      base. Upward migration of the spine may cause compression of the brainstem,
      mechanical impingement of the spinal canal with restriction of cerebrospinal
      fluid circulation, and impingement of the cranial nerves. Osteogenesis imperfecta
      also may directly involve neurovascular structures, leading to cavernous fistulas
      of the carotid artery, dissection of the cervical arteries, and cerebral
      aneurysms. The brain parenchyma is frequently affected by the disease, with
      manifestations including cerebral atrophy, communicating hydrocephalus, and
      cerebellar hypoplasia. The imaging features of the disorder vary as widely as its
      clinical manifestations, depending on the severity of disease. Severe forms
      accompanied by debilitating skeletal fractures and progressive neurologic
      impairments may lead to perinatal death, whereas milder asymptomatic forms might
      cause only a modest reduction in life span. The most important advance in medical
      therapy for osteogenesis imperfecta has been the introduction of bisphosphonate
      therapy to slow the resorption of bone in patients with moderate to severe forms
      of the disease (ie, type III or IV). In some patients, neurosurgery may be
      necessary to correct the effects of severe basilar invagination by the odontoid
      process.

PMID- 23150861
TI  - Quality initiatives: statistical control charts: simplifying the analysis of data
      for quality improvement.
AB  - Quality improvement (QI) projects are an integral part of today's radiology
      practice, helping identify opportunities for improving outcomes by refining work
      processes. QI projects are typically driven by outcome measures, but the data can
      be difficult to interpret: The numbers tend to fluctuate even before a process is
      altered, and after a QI intervention takes place, it may be even more difficult
      to determine the cause of such vacillations. Control chart analysis helps the QI
      project team identify variations that should be targeted for intervention and
      avoid tampering in processes in which variation is random or harmless.
      Statistical control charts make it possible to distinguish among random variation
      or noise in the data, outlying tendencies that should be targeted for future
      intervention, and changes that signify the success of previous intervention. The
      data on control charts are plotted over time and integrated with various graphic
      devices that represent statistical reasoning (eg, control limits) to allow
      visualization of the intensity and overall effect-negative or positive-of
      variability. Even when variability has no substantial negative effect,
      appropriate intervention based on the results of control chart analysis can help
      increase the efficiency of a process by optimizing the central tendency of the
      outcome measure. Different types of control charts may be used to analyze the
      same outcome dataset: For example, paired charts of individual values (x) and the
      moving range (mR) allow robust and reliable analyses of most types of data from
      radiology QI projects. Many spreadsheet programs and templates are available for
      use in creating x-mR charts and other types of control charts.

PMID- 23150862
TI  - Scenes from the past: CT-guided endoscopic recovery of a foreign object from the
      cranial cavity of an ancient Egyptian mummy.
AB  - The aim of this study was to test the value of computed tomography (CT)-guided
      endoscopy in the scientific study of mummified remains and the recovery of
      unidentified objects from ancient mummified remains. CT-guided endoscopy was
      performed on an Egyptian mummy from the Late Period to help retrieve an
      unidentified object from its skull. The combined use of CT and endoscopy
      facilitated the recovery of the object, minimizing further damage to the remains
      and to the object itself. The successful recovery of the brittle object allowed
      detailed analysis of the item to be performed in an attempt to determine the
      nature of its presence in the cranial cavity. It was confirmed that the object
      was a monocotyledon stem fragment. Relying on the existing literature on
      mummification and excerebration methods in ancient Egypt, we concluded that the
      stick was probably used for transnasal removal of the brain. The results of this
      study demonstrate the great potential of CT-guided endoscopy for minimally
      invasive recovery of small unidentified items from mummies that could yield
      important information about mummification procedures and the materials used to
      preserve bodies.

PMID- 23150863
TI  - Cystic lesions of the pancreas: radiologic-endosonographic correlation.
AB  - Cystic lesions of the pancreas are relatively common findings at cross-sectional
      imaging; however, classification of these lesions on the basis of imaging
      features alone can sometimes be difficult. Complementary evaluation with
      endoscopic ultrasonography and fine-needle aspiration may be helpful in the
      diagnosis of these lesions. Cystic lesions of the pancreas may range from benign
      to malignant and include both primary cystic lesions of the pancreas (including
      intraductal papillary mucinous neoplasms, mucinous cystic neoplasms, serous
      cystadenomas, pseudocysts, and true epithelial cysts) and solid neoplasms
      undergoing cystic degeneration (including neuroendocrine tumors, solid
      pseudopapillary neoplasms, and, rarely, adenocarcinoma and its variants).
      Familiarity with the imaging features of these lesions and the basic treatment
      algorithms is essential for radiologists, as collaboration with
      gastroenterologists and surgeons is often necessary to obtain an early and
      accurate diagnosis.

PMID- 23150864
TI  - MR imaging of thoracic abnormalities in the fetus.
AB  - In recent years, with the development of ultrafast sequences, magnetic resonance
      (MR) imaging has been established as a valuable diagnostic modality complementary
      to ultrasonography (US). MR imaging offers several technical advantages over US,
      including a larger field of view, fewer limitations due to maternal habitus, and
      the ability to visualize fetal anatomy regardless of fetal presentation. The
      authors discuss the most frequently found thoracic abnormalities, including
      congenital diaphragmatic hernia, congenital cystic adenomatoid malformation,
      bronchopulmonary sequestration, bronchogenic cyst, congenital high airway
      obstruction syndrome, and bronchial obstruction by a mucus plug, specifically
      with respect to the effect of fetal MR imaging on diagnosis and treatment. MR
      imaging can assist in establishing the prognosis and in perinatal management,
      especially in the case of congenital diaphragmatic hernia, which is the most
      common indication for thoracic MR imaging. MR imaging can demonstrate hernial
      contents and quantify lung volume better than US, allowing the prognosis to be
      determined and postpartum extracorporeal membrane oxygenation needs to be
      estimated. MR imaging can also be used to distinguish different types of cystic
      adenomatoid malformations, identify the anomalous vessels of pulmonary
      sequestration, and assess the functional effects of bronchogenic cysts. Balanced
      sequences (steady-state free precession sequences) allow performance of
      unenhanced thoracic vascular studies, which are useful in the diagnosis of
      intralobar or extralobar sequestration. In summary, fetal MR imaging can provide
      additional data useful in establishing prognosis and in perinatal management of
      thoracic malformations.

PMID- 23150865
TI  - Stereoscopic digital mammography: improved specificity and reduced rate of recall
      in a prospective clinical trial.
AB  - PURPOSE: To compare stereoscopic digital mammography (DM) with standard DM for
      the rate of patient recall and the detection of cancer in a screening population
      at elevated risk for breast cancer. MATERIALS AND METHODS: Starting in September
      2004 and ending in December 2007, this prospective HIPAA-compliant, institutional
      review board-approved screening trial, with written informed consent, recruited
      female patients at elevated risk for breast cancer (eg, personal history of
      breast cancer or breast cancer in a close relative). A total of 1298 examinations
      from 779 patients (mean age, 58.6 years; range, 32-91 years) comprised the
      analyzable data set. A paired study design was used, with each enrolled patient
      serving as her own control. Patients underwent both DM and stereoscopic DM
      examinations in a single visit, findings of which were interpreted independently
      by two experienced radiologists, each using a Breast Imaging Reporting and Data
      System (BI-RADS) assessment (BI-RADS category 0, 1, or 2). All patients
      determined to have one or more findings with either or both modalities were
      recalled for standard diagnostic evaluation. The results of 1-year follow-up or
      biopsy were used to determine case truth. RESULTS: Compared with DM, stereoscopic
      DM showed significantly higher specificity (91.2% [1167 of 1279] vs 87.8% [1123
      of 1279]; P = .0024) and accuracy (90.9% [1180 of 1298] vs 87.4% [1135 of 1298];
      P = .0023) for detection of cancer. Sensitivity for detection of cancer was not
      significantly different for stereoscopic DM (68.4% [13 of 19]) compared with DM
      (63.2% [12 of 19], P .99). The recall rate for stereoscopic DM was 9.6% (125 of
      1298) and that for DM was 12.9% (168 of 1298) (P = .0018). CONCLUSION: Compared
      with DM, stereoscopic DM significantly improved specificity for detection of
      cancer, while maintaining comparable sensitivity. The recall rate was
      significantly reduced with stereoscopic DM compared with DM. SUPPLEMENTAL
      MATERIAL: http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.12120382/
      /DC1.

PMID- 23150867
TI  - Modern treatment planning approach facing a failure of conventional treatment.
      Part I: Analysis of treatment options.
AB  - In this two-part case presentation, the benchmarks of our treatment planning
      principles are briefly explained and their application is discussed in the case
      of a 35-year old patient with multiple failing restorations and an esthetic
      complaint regarding the maxillary anterior teeth. In this first part, the four
      principles are proposed, the patient's main problems are presented and three
      treatment options are discussed. In the second part, the treatment choice will be
      disclosed as well as the decision making process, the respective diagnostic
      procedures involved, and finally the sequential treatment. The aim of these
      articles is to stimulate the debate and to promote therapeutic choices that take
      into account evolution of contemporary dental medicine.

PMID- 23150868
TI  - The autogenous immediate implant supported single-tooth restoration: a 5-year
      follow-up.
AB  - When replacing a missing tooth in the esthetic zone, the implant supported single
      tooth restoration can result in a very natural and pleasing solution for the
      patient, being also a conservative procedure that preserves the adjacent
      remaining dentition. Immediate implant placement with an immediate provisional
      crown can avoid stressful and uncomfortable healing time for the patient who no
      longer has to wear an interim removable appliance. In selected clinical
      situations, excellent tooth esthetics for implant supported single tooth
      restorations can be achieved by using the natural extracted tooth as both
      provisional and final restoration. No longterm data is available today as far as
      the survival rate of such restorations and the predictability of such a treatment
      modality. This case report describes a technique for utilizing the patient's
      extracted tooth for the fabrication of an inconspicuous final anterior
      restoration, reporting a 5-year follow-up.

PMID- 23150869
TI  - Mechanical, biological and clinical aspects of zirconia implants.
AB  - The objective of this narrative overview is to discuss several in vitro and in
      vivo studies regarding the performance of one-piece zirconia implants in
      combination with the description of two clinical scenarios where zirconia implant
      prototypes were utilized with emphasis on the possible scientific and clinical
      concerns that may affect the functional, biological and esthetic long-term
      outcomes.

PMID- 23150870
TI  - Identification of monoclinic phase in CAD/CAM zirconia FPD frameworks.
AB  - OBJECTIVE: The aim of this study was to identify the presence of monoclinic
      zirconia phase (m-ZrO2) in 5 computeraided design/computer-assisted manufacture
      zirconia systems composed of yttria-stabilized tetragonal zirconia polycrystals
      (Y-TZP). MATERIALS AND METHODS: Three-unit fixedpartial dentures were prepared
      from Cercon (CR); Lava (LW); Zenotec Zr Bridge (WD); In-Ceram YZ (YZ); and IPS e
      max ZirCAD (ZC), all milled in a pre-sintered stage and then fully sintered
      according to the manufacturers' instructions. Raman spectroscopy was used to
      identify and map the distribution of the m-ZrO2 phase at cervical crown margins,
      pontic and connector regions. Three sets of data were obtained from each material
      (n = 2) and the percentage volume (%Vm) of the m-ZrO2 phase was calculated per
      region. Statistical analysis was performed by two-way analysis of variance and
      Tukey test (a = 0.05). RESULTS: The m-ZrO2 phase was detected in all the
      specimens, with the highest intensity located at the crown margins. WD showed the
      lowest %Vm content (0- 3.14%), followed by LW (10.26-12.39%), CR (11.72-13.19%),
      ZC (11.13-14.10%) and YZ (12.15-14.99%). No statistically significant difference
      was found among LW, CR, ZC, YZ per region. Within each material group,
      significant differences were found between margin-pontic/connector (WD, YZ),
      margin-connector (CR, ZC) and margin-pontic (LW). SIGNIFICANCE: The Y-TZP
      destabilizing m-ZrO2 phase was identified in all the fully sintered frameworks
      tested, with the highest %Vm located at the margins. The extent to which the
      presence of this phase may be implicated with zirconia low temperature
      degradation or porcelain to zirconia bonding is unknown.

PMID- 23150871
TI  - Comparative study between the radiopacity levels of high viscosity and of
      flowable composite resins, using digital imaging.
AB  - INTRODUCTION: The development of countless types and trends of high viscosite and
      flowable composite resins, with different physical and chemical properties
      applicable to their broad use in dental clinics calls for further studies
      regarding their radiopacity level. PURPOSE OF THE STUDY: The aim of this study
      was to evaluate the radiopacity levels of high viscosity and the flowable
      composite resins, using digital imaging. MATERIALS AND METHODS: 96 composite
      resin discs 5 mm in diameter and 3 mm thick were radiographed and analyzed. The
      image acquisition system used was the Digora(r) Phosphor Storage System and the
      images were analyzed with the Digora software for Windows. The exposure
      conditions were: 70 kVp, 8 mA, and 0.2 s. The focal distance was 40 cm. The image
      densities were obtained with the pixel values of the materials in the digital
      image. RESULTS: Most of the high viscosity composite resins presented higher
      radiopacity levels than the flowable composite resins, with statistically
      significant differences between the trends and groups analyzed (P < 0.05).
      CONCLUSIONS: Among the high viscosity composite resins, Tetric(r)Ceram presented
      the highest radiopacity levels and Glacier(r) presented the lowest. Among the
      flowable composite resins, Tetric(r)Flow presented the highest radiopacity levels
      and Wave(r) presented the lowest.

PMID- 23150872
TI  - The occurrence of phi in dento-facial beauty of fine art from antiquity through
      the Renaissance.
AB  - External beauty is a complex construct that influences lives and may be impacted
      by dentists. Beauty is not easily quantified, but one cited anthropometric of
      beauty is the ratio phi, the number 1.618033(...). This study examined phi as a
      measure of female frontal facial beauty in classic Western art, using pre-
      Renaissance (N = 30), and Renaissance (N = 30) artwork. Four horizontal and five
      vertical ratios were determined in the works of art, which were then compared
      with the phi ratio. All horizontal ratios for both pre-Renaissance and
      Renaissance artwork were similar to each other, but did not contain the phi ratio
      (P < 0.001). Nevertheless, all vertical ratios for pre-Renaissance and
      Renaissance art-work did contain the phi ratio within their confidence intervals
      with the exception of the vertical ratio, "intereye point to soft tissue menton/
      intereye point to stomion", that was found to be less than phi in the Renaissance
      group. The study provides evidence of the presence of the phi ratio in vertical
      aspect of females in artwork from pre-Renaissance through the Renaissance
      demonstrating consistent temporal preferences. Therefore, the phi ratio seems to
      be an important consideration in altering vertical facial dimensions in full
      mouth rehabilitation and reconstructive orthognathic surgery involving females.

PMID- 23150873
TI  - The effects of forehead and neck positions on profile esthetics.
AB  - INTRODUCTION: Each facial feature might affect the perception of the balance of
      the other features so the whole of the face must be considered in facial
      evaluation. There are no studies that have examined the effect of forehead and
      neck position on profile esthetics. The objective of this study was to evaluate
      the effects of forehead and neck positions on profile esthetics judged by lay
      people, dental students and art students. MATERIALS AND METHODS: A straight
      silhouette (black right-facing profile in white background) was digitally
      manipulated to make variations of profiles. The positions of all compartments of
      face were similar except for anteroposterior position of forehead and neck. The
      310 raters (100 dental students, 100 art students and 110 lay people) were asked
      to rate profiles with a Likert scale. The nonparametric Mann-Whitney test,
      chisquare tests, Spearman rank correlation coefficients, one-way analysis of
      variance (ANOVA) and Kruskal-Wallis analyses were used in data analysis. RESULTS:
      The scores given to profiles with straight, retruded and protruded necks and
      foreheads were significantly different. (P < 0.05). In three groups, the most and
      least attractive profiles judged by raters were comparable (P > 0.05).
      CONCLUSION: This study showed that the position of the forehead and the neck has
      an effect on the beauty of profile silhouettes and this effect is so noticeable
      that all of the raters could perceive the differences. It is necessary to
      evaluate the whole of the face, including the forehead and neck, in a facial
      evaluation.

PMID- 23150875
TI  - Detection of cancer cells using a peptide nanotube-folic acid modified graphene
      electrode.
AB  - This article describes the preparation of a graphene electrode modified with a
      new conjugate of peptide nanotubes and folic acid for the selective detection of
      human cervical cancer cells over-expressing folate receptors. The
      functionalization of peptide nanotubes with folic acid was confirmed by
      fluorescence microscopy and atomic force microscopy. The peptide nanotube-folic
      acid modified graphene electrode was characterized by scanning electron
      microscopy and cyclic voltammetry. The modification of the graphene electrode
      with peptide nanotube-folic acid led to an increase in the current signal. The
      human cervical cancer cells were bound to the modified electrode through the
      folic acid-folate receptor interaction. Cyclic voltammograms in the presence of
      [Fe(CN)(6)](3-/4-) as a redox species demonstrated that the binding of the folate
      receptor from human cervical cancer cells to the peptide nanotube-folic acid
      modified electrode lowered the electron transfer resulting in a decrease in the
      measured current. A detection limit of 250 human cervical cancer cells per mL was
      obtained. Control experiments confirmed that the peptide nanotube-folic acid
      electrode specifically recognized folate receptors. The modified electrode
      described here opens up new possibilities for future applications in early stage
      diagnoses of diseases where cells over-express folate receptors, such as in
      cancer or leishmaniasis disease.

PMID- 23150874
TI  - Human TNRC6A is an Argonaute-navigator protein for microRNA-mediated gene
      silencing in the nucleus.
AB  - GW182 family proteins play important roles in microRNA (miRNA)-mediated gene
      silencing. They interact with Argonaute (Ago) proteins and localize in processing
      bodies, which are cytoplasmic foci involved in mRNA degradation and storage.
      Here, we demonstrated that human GW182 paralog, TNRC6A, is a nuclear-cytoplasmic
      shuttling protein, and its subcellular localization is conducted by a nuclear
      export signal (NES) and a nuclear localization signal (NLS) identified in this
      study. TNRC6A with mutations in its NES region was predominantly localized in the
      nucleus in an Ago-independent manner. However, it was found that TNRC6A could
      bring Ago protein into the nucleus via its Ago-interacting motif(s). Furthermore,
      miRNAs were also colocalized with nuclear TNRC6A-Ago and exhibited gene silencing
      activity. These results proposed the possibility that TNRC6A plays an important
      role in navigating Ago protein into the nucleus to lead miRNA-mediated gene
      silencing.

PMID- 23150877
TI  - Asymmetric binary acid catalysis: chiral phosphoric acid as dual ligand and acid.
AB  - Recently, chiral Bronsted acids as dual ligand and acid catalysts in the context
      of metal catalysis have been developed. Such binary catalytic systems
      synergistically integrate chiral Bronsted acids and metal catalysts as a result
      of their weakly coordinating behaviors. The resulting binary acid catalysts have
      enabled effective reactions of a range of olefins/aromatics, beyond the scope of
      typical acid catalysis. Our endeavors in developing asymmetric binary acid
      catalysis are summarized in this feature article.

PMID- 23150876
TI  - Toward development of a surface-enhanced Raman scattering (SERS)-based cancer
      diagnostic immunoassay panel.
AB  - Proteomic analyses of readily obtained human fluids (e.g., serum, urine, and
      saliva) indicate that the diagnosis of complex diseases will be enhanced by the
      simultaneous measurement of multiple biomarkers from such samples. This paper
      describes the development of a nanoparticle-based multiplexed platform that has
      the potential for simultaneous read-out of large numbers of biomolecules. For
      this purpose, we have chosen pancreatic adenocarcinoma (PA) as a test bed for
      diagnosis and prognosis. PA is a devastating form of cancer in which an estimated
      86% of diagnoses resulted in death in the United States in 2010. The high
      mortality rate is due, in part, to the asymptomatic development of the disease
      and the dearth of sensitive diagnostics available for early detection. One
      promising route lies in the development of a serum biomarker panel that can
      generate a signature unique to early stage PA. We describe the design and
      development of a proof-of-concept PA biomarker immunoassay array coupled with
      surface-enhanced Raman scattering (SERS) as a sensitive readout method.

PMID- 23150878
TI  - Supramolecular approaches to metal-organic gels using 'Chevrel-type' coordination
      clusters as building units.
AB  - A novel hexanuclear {Mn(6)} coordination complex with octahedral topology has
      been prepared and was subsequently used as a building unit for the construction
      of coordination polymers and metal-organic gels; the latter exhibit thixotropic
      behavior and reversible sol-gel phase transitions.

PMID- 23150879
TI  - PTEN: an intercellular peacekeeper?
AB  - It is generally assumed that cells synthesize their own intracellular enzymes.
      Therefore, if expression of a specific gene is silenced in a potential cancer
      cell, it is expected that loss of protein function will follow. A provocative
      study indicates an unexpected mechanism of intercellular tumor suppression,
      showing that PTEN (phosphatase and tensin homolog deleted from chromosome 10), a
      cytosolic enzyme, can be transferred between cells in exosomes to suppress
      signaling and proliferation in target cells.

PMID- 23150880
TI  - Single amino acid substitutions confer the antiviral activity of the TRAF3
      adaptor protein onto TRAF5.
AB  - The TRAF [tumor necrosis factor receptor-associated factor] family of cytoplasmic
      adaptor proteins link cell-surface receptors to intracellular signaling pathways
      that regulate innate and adaptive immune responses. In response to activation of
      RIG-I (retinoic acid-inducible gene I), a component of a pattern recognition
      receptor that detects viruses, TRAF3 binds to the adaptor protein Cardif [caspase
      activation and recruitment domain (CARD) adaptor-inducing interferon-beta (IFN
      beta)], leading to induction of type I IFNs. We report the crystal structures of
      the TRAF domain of TRAF5 and that of TRAF3 bound to a peptide from the TRAF
      interacting motif of Cardif. By comparing these structures, we identified two
      residues located near the Cardif binding pocket in TRAF3 (Tyr(440) and Phe(473))
      that potentially contributed to Cardif recognition. In vitro and cellular
      experiments showed that forms of TRAF5 with mutation of the corresponding
      residues to those of TRAF3 had TRAF3-like antiviral activity. Our results provide
      a structural basis for the critical role of TRAF3 in activating RIG-I-mediated
      IFN production.

PMID- 23150881
TI  - The tetraspanin CD37 orchestrates the alpha(4)beta(1) integrin-Akt signaling axis
      and supports long-lived plasma cell survival.
AB  - Signaling by the serine and threonine kinase Akt (also known as protein kinase
      B), a pathway that is common to all eukaryotic cells, is central to cell
      survival, proliferation, and gene induction. We sought to elucidate the
      mechanisms underlying regulation of the kinase activity of Akt in the immune
      system. We found that the four-transmembrane protein CD37 was essential for B
      cell survival and long-lived protective immunity. CD37-deficient (Cd37(-/-)) mice
      had reduced numbers of immunoglobulin G (IgG)-secreting plasma cells in lymphoid
      organs compared to those in wild-type mice, which we attributed to increased
      apoptosis of plasma cells in the germinal centers of the spleen, areas in which B
      cells proliferate and are selected. CD37 was required for the survival of IgG
      secreting plasma cells in response to binding of vascular cell adhesion molecule
      1 to the alpha(4)beta(1) integrin. Impaired alpha(4)beta(1) integrin-dependent
      Akt signaling in Cd37(-/-) IgG-secreting plasma cells was the underlying cause
      responsible for impaired cell survival. CD37 was required for the mobility and
      clustering of alpha(4)beta(1) integrins in the plasma membrane, thus regulating
      the membrane distribution of alpha(4)beta(1) integrin necessary for activation of
      the Akt survival pathway in the immune system.

PMID- 23150882
TI  - MOFs for CO2 capture and separation from flue gas mixtures: the effect of
      multifunctional sites on their adsorption capacity and selectivity.
AB  - Microporous metal-organic frameworks (MOFs) have attracted tremendous attention
      because of their versatile structures and tunable porosity that allow almost
      unlimited ways to improve their properties and optimize their functionality,
      making them very promising for a variety of important applications, especially in
      the adsorption and separation of small gases and hydrocarbons. Numerous studies
      have demonstrated that MOFs with multifunctional groups, such as open metal sites
      (OMSs) and Lewis basic sites (LBSs), interact strongly with carbon dioxide and
      are particularly effective in its capture and separation from binary mixtures of
      CO(2) and N(2). In this feature article, we briefly review the current state of
      MOF development in this area, with an emphasis on the effect of multifunctional
      groups on the selectivity and capacity of MOFs for the CO(2) capture from flue
      gas mixtures.

PMID- 23150884
TI  - One-step synthesis of alloyed dual-emitting semiconductor nanocrystals.
AB  - Alloyed Zn(1-x-y)Cd(x)Mn(y)Se nanocrystals exhibiting bright intrinsic dual
      emission attractive for ratiometric optical nanothermometry are reported.
      Relative to earlier materials with related dual emission, these alloy
      nanocrystals require shorter syntheses, contain less Cd(2+), and show dual
      emission that is less sensitive to nanocrystal shape, size, or surfaces.

PMID- 23150883
TI  - The emergency medical services safety champions.
AB  - The overarching mission of prehospital emergency medical services (EMS) is to
      deliver lifesaving care for people when their needs are greatest. Fulfilling this
      mission is challenged by threats to patient and provider safety. The EMS setting
      is a high-risk one because care is delivered rapidly in the out-of-hospital
      setting where resources of benefit to patients are limited. There is growing
      evidence that safety culture varies widely across EMS agencies. A poor safety
      culture may manifest as error in medication, back injuries, and other poor
      outcomes for patient and provider. Recently, federal and national leaders of EMS
      (ie, the National Highway Traffic Safety Administration) have made improving EMS
      safety culture a national priority. Unfortunately, few initiatives can help local
      EMS leaders achieve that priority. The authors describe the successful EMS Champs
      Fellowship program, supported by the Jewish Healthcare Foundation, designed to
      train EMS leaders to improve safety for patients and providers. 

PMID- 23150885
TI  - Proceedings of the Christiana Care Health System Value Institute Value Symposium.

PMID- 23150886
TI  - Total syntheses of mitragynine, paynantheine and speciogynine via an
      enantioselective thiourea-catalysed Pictet-Spengler reaction.
AB  - The pharmacologically interesting indole alkaloids (-)-mitragynine, (+)
      paynantheine and (+)-speciogynine were synthesised in nine steps from 4
      methoxytryptamine by a route featuring (i) an enantioselective thiourea-catalysed
      Pictet-Spengler reaction, providing the tetrahydro-beta-carboline ring and (ii) a
      Pd-catalysed Tsuji-Trost allylic alkylation, closing the D-ring.

PMID- 23150887
TI  - DNA-induced chirality in water-soluble poly(cobaltoceniumethylene).
AB  - Poly(cobaltoceniumethylene), a water-soluble cationic metal-containing
      polyelectrolyte, adopts a chiral structure when bound electrostatically to DNA.

PMID- 23150888
TI  - Pitch discrimination and melodic memory in children with autism spectrum
      disorders.
AB  - BACKGROUND: Pitch perception is enhanced among persons with autism. We extended
      this finding to memory for pitch and melody among school-aged children.
      OBJECTIVE: The purpose of this study was to investigate pitch memory in musically
      untrained children with autism spectrum disorders, aged 7-13 years, and to
      compare it to that of age- and IQ-matched typically developing children. METHODS:
      The children were required to discriminate isolated tones in two differing
      contexts as well to remember melodies after a period of 1 week. The tasks were
      designed to employ both short- and long-term memory for music. For the pitch
      discrimination task, the children first had to indicate whether two isolated
      tones were the same or different when the second was the same or had been altered
      to be 25, 35, or 45 cents sharp or flat. Second, the children discriminated the
      tones within the context of melody. They were asked whether two melodies were the
      same or different when the leading tone of the second melody was the same or had
      been altered to be 25, 35, or 45 cents sharp or flat. Long-term memory for melody
      was also investigated, as the children attempted to recall four different two-bar
      melodies after 1 week. RESULTS: The children with autism spectrum disorders
      demonstrated elevated pitch discrimination ability in the single-tone and melodic
      context as well as superior long-term memory for melody. Pitch memory correlated
      positively with scores on measures of nonverbal fluid reasoning ability.
      CONCLUSION: Superior short- and long-term pitch memory was found among children
      with autism spectrum disorders. The results indicate an aspect to cognitive
      functioning that may predict both enhanced nonverbal reasoning ability and
      atypical language development.

PMID- 23150889
TI  - Axonal loss of white matter in migraine without aura: a tract-based spatial
      statistics study.
AB  - AIM: Multiple diffusion tensor imaging (DTI) derived indices may help to deduce
      the pathophysiological type of white matter (WM) changes and provide more
      specific biomarkers of WM neuropathology in the whole brain of migraine patients
      without aura (MWoA). METHODS: Twenty MWoA and 20 age-, education- and gender
      matched healthy volunteers participated in this study. Tract-based spatial
      statistics (TBSS) was employed to investigate the WM abnormalities in MWoA by
      integrating multiple indices, including fractional anisotropy (FA), mean
      diffusivity (MD), radial diffusivity (RD), and axial diffusivity (AD). RESULTS:
      Compared with healthy controls, MWoA showed significantly lower FA, MD and AD in
      multiple brain regions, whereas no difference in RD was observed. Specifically,
      the overlap among the lower FA, MD, and AD was found in the genu, body, and
      splenium part of the corpus callosum (CC), the right anterior limb of the
      internal capsule (ALIC) and the posterior limb of the internal capsule (PLIC) in
      MWoA compared with healthy controls. Additionally, some of the above WM findings
      were significantly correlated with duration and headache frequency in MWoA.
      CONCLUSION: Given that decreased AD may suggest axonal loss, our findings may
      reveal axonal loss in MWoA.

PMID- 23150890
TI  - Ophthalmoplegic migraine: migraine or oculomotor neuropathy?
AB  - BACKGROUND: Ophthalmoplegic migraine (OM) is a rare condition characterized by
      the association of headaches and an oculomotor nerve palsy. The third cranial
      nerve is commonly involved in recurrent attacks, whereas involvement of the sixth
      and fourth nerves is uncommon. It is still debated whether an uncontrolled
      migraine or an oculomotor neuropathy may be the primary cause of ophthalmoplegic
      migraine. CASES: We report two patients affected by OM with normal magnetic
      resonance imaging findings and a history of uncontrolled migraine before an
      attack of OM. CONCLUSION: The cases reported allow us to hypothesize that OM may
      be considered a form of migraine rather than a cranial neuralgia. It is possible
      that different factors such as inflammatory or structural factors, may represent
      a vulnerability of the nerve during a severe migraine attack causing
      ophthalmoplegia.

PMID- 23150891
TI  - Circulating microRNA-126 increases after different forms of endurance exercise in
      healthy adults.
AB  - BACKGROUND: MicroRNAs (miRNAs) are small non-coding molecules regulating gene
      expression. Recently circulating miRNAs could be detected in the plasma, serving
      as novel biomarkers. Different forms of exercise mobilize progenitor cells from
      the bone marrow, helping in tissue repair. Data of different forms of exercise on
      endothelial cell damage are lacking. The aim of the study was to evaluate the
      impact of different exercise modalities on the plasma concentration of miRNA-126,
      as a marker for endothelial damage. METHODS: The plasma concentration of miRNA
      126 and miRNA-133 (marker for muscle damage) was assessed by qRT-PCR analysis in
      plasma samples from healthy individuals performing one of the following exercise
      tests: (1) maximal symptom-limited exercise test, (2) bicycling for 4 h, (3)
      running a marathon, and (4) resistance exercise. RESULTS: A maximal symptom
      limited exercise test resulted in a significant increase of circulating miRNA-126
      at maximum power (2.1-fold versus begin), whereas the concentration of miRNA-133
      remained unchanged. In line, four hours of cycling increased plasma concentration
      of miRNA-126 with a maximum 30 minutes after begin (4.6-fold versus begin)
      without an impact on miRNA-133 concentration. Finishing a marathon race resulted
      in an increase of miRNA-126 and miRNA-133. In contrast, eccentric resistance
      training led to an isolated increase of miRNA-133 level (2.1-fold versus begin)
      with unchanged miRNA-126. CONCLUSION: Different endurance exercise protocols lead
      to damage of the endothelial cell layer as evident by an increase in miRNA-126.
      On the other hand, resistance exercise has no impact on the endothelial cells,
      but leads to a destruction of muscular cells.

PMID- 23150893
TI  - Role of Fe-N-C geometry flip-flop in bistability in Fe(tetrazol-2-yl)4(C2H5CN)2
      type core based coordination network.
AB  - [Fe(ebtz)(2)(C(2)H(5)CN)(2)](ClO(4))(2) was prepared in the reaction of 1,2
      di(tetrazol-2-yl)ethane (ebtz) with Fe(ClO(4))(2).6H(2)O in propionitrile. The
      compound crystallizes as a one-dimensional (1D) network, where bridging of
      neighboring iron(II) ions by two ebtz ligand molecules results in formation of a
      [Fe(ebtz)(2)](infinity) polymeric skeleton. The 1D chains are assembled into
      supramolecular layers with axially coordinated nitrile molecules directed
      outward. The complex in the high spin (HS) form reveals a very rare feature,
      namely, a bent geometry of the Fe-N-C(propionitrile) fragment (149.1(3) degrees 
      at 250 K). The HS to low spin (LS) HS->LS transition triggers reorientation of
      the propionitrile molecule resulting in accommodation of a typical linear
      geometry of the Fe-N-C(nitrile) fragment. The switching of the propionitrile
      molecule orientation in relation to the coordination octahedron is associated
      with increase of the distance between the supramolecular layers. When the crystal
      is in the LS phase, raising the temperature does not cause reduction of the
      distance between supramolecular layers, which contributes to further
      stabilization of the more linear geometry of Fe-N-C(C(2)H(5)) and the LS form of
      the complex. Thus, a combination of Fe-N-C(C(2)H(5)) geometry lability and
      lattice effects contributes to the appearance of hysteretic behavior (T(1/2)(?) ~
      112 K, T(1/2)(?) ~ 141 K).

PMID- 23150892
TI  - Development of isotope labeling LC-MS for human salivary metabolomics and
      application to profiling metabolome changes associated with mild cognitive
      impairment.
AB  - Saliva is a readily available biofluid that may contain metabolites of interest
      for diagnosis and prognosis of diseases. In this work, a differential (13)C/(12)C
      isotope dansylation labeling method, combined with liquid chromatography Fourier
      transform ion cyclotron resonance mass spectrometry (LC-FTICR-MS), is described
      for quantitative profiling of the human salivary metabolome. New strategies are
      presented to optimize the sample preparation and LC-MS detection processes. The
      strategies allow the use of as little of 5 MUL of saliva sample as a starting
      material to determine the concentration changes of an average of 1058 ion pairs
      or putative metabolites in comparative saliva samples. The overall workflow
      consists of several steps including acetone-induced protein precipitation, (12)C
      dansylation labeling of the metabolites, and LC-UV measurement of the total
      concentration of the labeled metabolites in individual saliva samples. A pooled
      sample was prepared from all the individual samples and labeled with (13)C
      dansylation to serve as a reference. Using this metabolome profiling method, it
      was found that compatible metabolome results could be obtained after saliva
      samples were stored in tubes normally used for genetic material collection at
      room temperature, -20  degrees C freezer, and -80  degrees C freezer over a
      period of 1 month, suggesting that many saliva samples already collected in
      genomic studies could become a valuable resource for metabolomics studies,
      although the effect of much longer term of storage remains to be determined.
      Finally, the developed method was applied for analyzing the metabolome changes of
      two different groups: normal healthy older adults and comparable older adults
      with mild cognitive impairment (MCI). Top-ranked 18 metabolites successfully
      distinguished the two groups, among which seven metabolites were putatively
      identified while one metabolite, taurine, was definitively identified.

PMID- 23150894
TI  - The social and economic burden of stroke survivors in Italy: a prospective,
      incidence-based, multi-centre cost of illness study.
AB  - BACKGROUND: The aim of this study was to estimate the one-year societal costs due
      to a stroke event in Italy and to investigate variables associated with costs in
      different phases following hospital admission. METHODS: The patients were
      enrolled in 44 hospitals across the country and data on socio-demographic,
      clinical variables and resource consumption were prospectively surveyed for 411
      stroke survivors at admission, discharge and 3, 6 and 12 months post the event.
      We adopted a micro-costing procedure to identify cost generating components and
      the attribution of appropriate unit costs for three cost categories: direct
      healthcare, direct non-healthcare (including informal care costs) and
      productivity losses. The relation between costs of stroke management and socio
      demographic and clinical characteristics as well as disability levels was
      evaluated in a series of bivariate analyses using non parametric tests (Mann
      Whitney and Kruskal-Wallis). Multiple linear regression analyses were performed
      to determine predictors of costs incurred by stroke patients during the acute
      phase and follow-up of 1 year. RESULTS: On average, one-year healthcare and
      societal costs amounted to ?11,747 and ? 19,953 per stroke survivor,
      respectively. The major cost component of societal costs was informal care
      accounting for ? 6,656 (33.4% of total), followed by the initial hospitalisation,
      (? 5,573; 27.9% of total), rehabilitation during follow up (? 4,112; 20.6 %),
      readmissions (? 439) and specialist and general practioner visits (? 326). Mean
      drug costs per patient over the follow-up period was about ? 50 per month. Costs
      associated to the provision of paid and informal care followed different pattern
      and were persistent over time (ranging from ? 639 to ? 597 per month in the first
      and the second part of the year, respectively). Clinical variables (presence of
      diabetes mellitus and hemorrhagic stroke) were significant predictors of total
      healthcare costs while functional outcomes (Barthel Index and Modified Ranking
      Scale scores) were significantly associated with both healthcare and societal
      costs at one year. CONCLUSIONS: The significant role of informal care in stroke
      management and different distribution of costs over time suggest that appropriate
      planning should look at both incident and prevalent stroke cases to forecast
      health infrastructure needs and more importantly, to assure that stroke patients
      have adequate "social" support.

PMID- 23150895
TI  - Differentiating organic from conventional peppermints using chromatographic and
      flow injection mass spectrometric (FIMS) fingerprints.
AB  - High-performance liquid chromatography (HPLC) and flow injection mass
      spectrometric (FIMS) fingerprinting techniques were tested for their potential in
      differentiating organic and conventional peppermint samples. Ten organic and ten
      conventional peppermint samples were examined using HPLC-UV and FIMS methods.
      Principal component analysis (PCA) showed that both HPLC and FIMS fingerprints
      could determine the difference in the commercial organic and conventional
      peppermints. FIMS fingerprinting provided a rapid test to differentiate organic
      and conventional peppermints in 1 min of analysis and has potential for high
      throughput applications. On the other hand, HPLC fingerprints provide more
      information about the chemical composition of the samples, but take a longer time
      to differentiate organic and conventional peppermint samples.

PMID- 23150896
TI  - Colloidal graphene quantum dots with well-defined structures.
AB  - When the size of a semiconductor crystal is reduced to the nanometer scale, the
      crystal boundary significantly modifies electron distribution, making properties
      such as bandgap and energy relaxation dynamics size dependent. This phenomenon,
      known as quantum confinement, has been demonstrated in many semiconductor
      materials, leading to practical applications in areas such as bioimaging,
      photovoltaics, and light-emitting diodes. Graphene, a unique type of
      semiconductor, is a two-dimensional crystal with a zero bandgap and a zero
      effective mass of charge carriers. Consequently, we expect new phenomena from
      nanometer-sized graphene, or graphene quantum dots (QDs), because the energy of
      charge carriers in graphene follows size-scaling laws that differ from those in
      other semiconductors. From a chemistry point of view, graphene is made of carbon,
      an element for which researchers have developed a whole branch of chemistry.
      Thus, it is possible to synthesize graphene QDs through stepwise, well-controlled
      organic chemistry, achieving structures with an atomic precision that has not
      been possible for any other semiconductor materials. Recently, we developed a new
      solubilizing strategy that led to synthesis of stable colloidal graphene QDs with
      more than 100 conjugated carbon atoms, allowing us to study their properties in a
      new size regime. In this Account, we review our recent progress working with the
      colloidal graphene QDs, including their synthesis and stabilization, tuning of
      their properties, and new phenomena in energy relaxation dynamics. In particular,
      we have observed extraordinarily slow "electron cooling"--the relaxation of
      electrons from high excited states to lower ones. With further investigation,
      these high-energy electrons could potentially be harvested in solar energy
      applications, for example, creating more efficient photovoltaic cells. We discuss
      additional emerging opportunities with these new materials and current
      challenges, hoping to draw the interest of researchers in various fields to
      overcome these obstacles.

PMID- 23150897
TI  - Functional networks in temporal-lobe epilepsy: a voxel-wise study of resting
      state functional connectivity and gray-matter concentration.
AB  - Temporal-lobe epilepsy (TLE) involves seizures that typically originate in the
      hippocampus. There is evidence that seizures involve anatomically and
      functionally connected brain networks within and beyond the temporal lobe. Many
      studies have explored the effect of TLE on gray matter and resting-state
      functional connectivity in the brain. However, the relationship between
      structural and functional changes has not been fully explored. The goal of this
      study was to investigate the relationship between gray matter concentration (GMC)
      and functional connectivity in TLE at the voxel level. A voxel-wise linear
      regression analysis was performed between GMC maps and whole-brain resting-state
      functional connectivity maps to both the left thalamus (Lthal) and the left
      hippocampus (LH) in a group of 15 patients with left TLE. Twenty regions were
      found that exhibited GMC decreases linearly correlated with resting-state
      functional connectivity to either the LH or the Lthal in the patient group only.
      A subset of these regions had significantly reduced GMC, and one of these regions
      also had reduced functional connectivity to the LH in TLE compared to the
      controls. These results suggest a network of impairment in left TLE where more
      severe reductions in GMC accompany decreases (LH, Lthal, right midcingulate
      gyrus, left precuneus, and left postcentral gyrus) or increases (LH to right
      thalamus) in resting functional connectivity. However, direct relationships
      between these imaging parameters and disease characteristics in these regions
      have yet to be established.

PMID- 23150899
TI  - Script-driven processing affords protection from retrieval-induced forgetting in
      the recall of everyday activities.
AB  - Using the retrieval-practice paradigm, we examined the effects of script and
      selective retrieval on the recall of high- and low-typicality actions of everyday
      activities. The participants studied two activities, Getting up in the morning
      and Going to a restaurant, each consisting of high-typicality and low-typicality
      actions. They then practised half of the high- or low-typicality actions of an
      activity, with recall of the unpractised activity serving as baseline. Script
      driven processing prompted the recall of high-typicality actions and produced
      more high-typicality than low-typicality intrusions. Selective retrieval practice
      of the high-typicality script actions did not have an adverse effect on the
      recall of high- or low-typicality actions, while practising low-typicality
      actions not representative of the scripts produced retrieval-induced forgetting
      of other low-typicality actions. Scripts provide the cognitive system with
      flexibility and economy, but side-effects such as high-typicality intrusions and
      poor memory for detail can also derive from script processing. 

PMID- 23150898
TI  - Evaluation of seven common lipid associated loci in a large Indian sib pair
      study.
AB  - BACKGROUND: Genome wide association studies (GWAS), mostly in Europeans have
      identified several common variants as associated with key lipid traits.
      Replication of these genetic effects in South Asian populations is important
      since it would suggest wider relevance for these findings. Given the rising
      prevalence of metabolic disorders and heart disease in the Indian sub-continent,
      these studies could be of future clinical relevance. METHODS: We studied seven
      common variants associated with a variety of lipid traits in previous GWASs. The
      study sample comprised of 3178 sib-pairs recruited as participants for the Indian
      Migration Study (IMS). Associations with various lipid parameters and
      quantitative traits were analyzed using the Fulker genetic association model.
      RESULTS: We replicated five of the 7 main effect associations with p-values
      ranging from 0.03 to 1.97x10(-7). We identified particularly strong association
      signals at rs662799 in APOA5 (beta=0.18 s.d, p=1.97 x 10(-7)), rs10503669 in LPL
      (beta =-0.18 s.d, p=1.0 x 10(-4)) and rs780094 in GCKR (beta=0.11 s.d, p=0.001)
      loci in relation to triglycerides. In addition, the GCKR variant was also
      associated with total cholesterol (beta=0.11 s.d, p=3.9x10(-4)). We also
      replicated the association of rs562338 in APOB (p=0.03) and rs4775041 in LIPC
      (p=0.007) with LDL-cholesterol and HDL-cholesterol respectively. CONCLUSIONS: We
      report associations of five loci with various lipid traits with the effect size
      consistent with the same reported in Europeans. These results indicate an overlap
      of genetic effects pertaining to lipid traits across the European and Indian
      populations.

PMID- 23150900
TI  - An efficient synthesis of symmetric and unsymmetric bis-(beta-aminoamides) via
      Ugi multicomponent reaction.
AB  - A library of symmetrical and unsymmetrical bis-(beta-aminoamides) has been
      prepared starting from symmetrical secondary diamines by using a double Ugi four
      component reaction. A sacrifical Mumm rearrangement, thanks to the use of 2
      hydroxymethyl benzoic acid, is necessary to suppress the competing split-Ugi
      reaction, increasing the yield and simplifying the purification step. The scope,
      the reaction conditions, and the role of water in trapping the nitrilium
      intermediate are also discussed.

PMID- 23150901
TI  - Tuberculosis and poverty: the contribution of patient costs in sub-Saharan Africa
      -a systematic review.
AB  - BACKGROUND: Tuberculosis (TB) is known to disproportionately affect the most
      economically disadvantaged strata of society. Many studies have assessed the
      association between poverty and TB, but only a few have assessed the direct
      financial burden TB treatment and care can place on households. Patient costs can
      be particularly burdensome for TB-affected households in sub-Saharan Africa where
      poverty levels are high; these costs include the direct costs of medical and non
      medical expenditures and the indirect costs of time utilizing healthcare or lost
      wages. In order to comprehensively assess the existing evidence on the costs that
      TB patients incur, we undertook a systematic review of the literature. METHODS:
      PubMed, EMBASE, Science Citation Index, Social Science Citation Index, EconLit,
      Dissertation Abstracts, CINAHL, and Sociological Abstracts databases were
      searched, and 5,114 articles were identified. Articles were included in the final
      review if they contained a quantitative measure of direct or indirect patient
      costs for treatment or care for pulmonary TB in sub-Saharan Africa and were
      published from January 1, 1994 to Dec 31, 2010. Cost data were extracted from
      each study and converted to 2010 international dollars (I$). RESULTS: Thirty
      articles met all of the inclusion criteria. Twenty-one studies reported both
      direct and indirect costs; eight studies reported only direct costs; and one
      study reported only indirect costs. Depending on type of costs, costs varied from
      less than I$1 to almost I$600 or from a small fraction of mean monthly income for
      average annual income earners to over 10 times average annual income for income
      earners in the income-poorest 20% of the population. Out of the eleven types of
      TB patient costs identified in this review, the costs for hospitalization,
      medication, transportation, and care in the private sector were largest.
      CONCLUSION: TB patients and households in sub-Saharan Africa often incurred high
      costs when utilizing TB treatment and care, both within and outside of Directly
      Observed Therapy Short-course (DOTS) programs. For many households, TB treatment
      and care-related costs were considered to be catastrophic because the patient
      costs incurred commonly amounted to 10% or more of per capita incomes in the
      countries where the primary studies included in this review were conducted. Our
      results suggest that policies to decrease direct and indirect TB patient costs
      are urgently needed to prevent poverty due to TB treatment and care for those
      affected by the disease.

PMID- 23150903
TI  - Comparison of walking overground and in a Computer Assisted Rehabilitation
      Environment (CAREN) in individuals with and without transtibial amputation.
AB  - BACKGROUND: Due to increased interest in treadmill gait training, recent research
      has focused on the similarities and differences between treadmill and overground
      walking. Most of these studies have tested healthy, young subjects rather than
      impaired populations that might benefit from such training. These studies also do
      not include optic flow, which may change how the individuals integrate sensory
      information when walking on a treadmill. This study compared overground walking
      to treadmill walking in a computer assisted virtual reality environment (CAREN)
      in individuals with and without transtibial amputations (TTA). METHODS: Seven
      individuals with traumatic TTA and 27 unimpaired controls participated. Subjects
      walked overground and on a treadmill in a CAREN at a normalized speed. The CAREN
      applied optic flow at the same speed that the subject walked. Temporal-spatial
      parameters, full body kinematics, and kinematic variability were collected during
      all trials. RESULTS: Both subject groups decreased step time and control subjects
      decreased step length when walking in the CAREN. Differences in lower extremity
      kinematics were small (< 2.5(?)) and did not exceed the minimal detectable change
      values for these measures. Control subjects exhibited decreased transverse and
      frontal plane range of motion of the pelvis and trunk when walking in the CAREN,
      while patients with TTA did not. Both groups exhibited increased step width
      variability during treadmill walking in the CAREN, but only minor changes in
      kinematic variability. CONCLUSIONS: The results of this study suggest that
      treadmill training in a virtual environment should be similar enough to
      overground that changes should carry over. Caution should be made when comparing
      step width variability and step time results from studies utilizing a treadmill
      to those overground.

PMID- 23150902
TI  - Genome-level identification, gene expression, and comparative analysis of porcine
      beta-defensin genes.
AB  - BACKGROUND: Beta-defensins (beta-defensins) are innate immune peptides with
      evolutionary conservation across a wide range of species and has been suggested
      to play important roles in innate immune reactions against pathogens. However,
      the complete beta-defensin repertoire in the pig has not been fully addressed.
      RESULT: A BLAST analysis was performed against the available pig genomic sequence
      in the NCBI database to identify beta-defensin-related sequences using previously
      reported beta-defensin sequences of pigs, humans, and cattle. The porcine beta
      defensin gene clusters were mapped to chromosomes 7, 14, 15 and 17. The gene
      expression analysis of 17 newly annotated porcine beta-defensin genes across 15
      tissues using semi-quantitative reverse transcription polymerase chain reaction
      (RT-PCR) showed differences in their tissue distribution, with the kidney and
      testis having the largest pBD expression repertoire. We also analyzed single
      nucleotide polymorphisms (SNPs) in the mature peptide region of pBD genes from 35
      pigs of 7 breeds. We found 8 cSNPs in 7 pBDs. CONCLUSION: We identified 29
      porcine beta-defensin (pBD) gene-like sequences, including 17 unreported pBDs in
      the porcine genome. Comparative analysis of beta-defensin genes in the pig genome
      with those in human and cattle genomes showed structural conservation of beta
      defensin syntenic regions among these species.

PMID- 23150904
TI  - Acute traumatic coagulopathy among major trauma patients in an urban tertiary
      hospital in sub Saharan Africa.
AB  - BACKGROUND: Mortality from trauma remains a major public health issue as it is
      the leading cause of death in persons aged 5 to 44 years. Uncontrolled hemorrhage
      and coagulopathy is responsible for over 50% of all trauma related deaths within
      the first 48 hrs of admission. Coagulation profiles are not routinely done among
      trauma patients in resource limited settings and there is a paucity of data on
      acute traumatic coagulopathy (ATC) in sub Saharan Africa. The study was conducted
      to evaluate the prothrombin time and partial thromboplastin time (PT/PTT) as
      predictors of mortality and morbidity among major trauma patients. METHODS: A
      prospective cohort study was carried out, in which major trauma patients admitted
      in A&E department between December 2011 to April 2012 were recruited. Five (5)
      mls of venous blood was drawn from a convenient vein within 10 minutes of the
      patient's arrival at A&E for analysis of PT/PTT. Patients were stratified into
      two groups by the presence/absence of coagulopathy then followed up for a 2 week
      period for morbidity and mortality. RESULTS: A total of 182 major trauma patients
      were recruited; 149 (81.9%) were males, the mean age was 29.5 years (SD 9.8).
      Prevalence of coagulopathy was 54% (98/182). The mean ISS for the ATC group was
      36.9 and the non ATC group was 26.9 (p=0.001). Patients with ATC stayed longer in
      hospital 11.24 days than non ATC patients 8 days (p=0.001). ATC was strongly
      associated with ARI (p= 0.003). Mortality was more in the ATC group 29 deaths
      compared to 9 deaths in the non ATC group. PTT was a strong independent predictor
      of mortality. CONCLUSION: A significant proportion of major trauma patients were
      coagulopathic. Initial coagulation profile is useful in predicting outcomes for
      major trauma patients.

PMID- 23150905
TI  - Scaffold fiber diameter regulates human tendon fibroblast growth and
      differentiation.
AB  - The diameter of collagen fibrils in connective tissues, such as tendons and
      ligaments is known to decrease upon injury or with age, leading to inferior
      biomechanical properties and poor healing capacity. This study tests the
      hypotheses that scaffold fiber diameter modulates the response of human tendon
      fibroblasts, and that diameter-dependent cell responses are analogous to those
      seen in healthy versus healing tissues. Particularly, the effect of the fiber
      diameter (320 nm, 680 nm, and 1.80 MUm) on scaffold properties and the response
      of human tendon fibroblasts were determined over 4 weeks of culture. It was
      observed that scaffold mechanical properties, cell proliferation, matrix
      production, and differentiation were regulated by changes in the fiber diameter.
      More specifically, a higher cell number, total collagen, and proteoglycan
      production were found on the nanofiber scaffolds, while microfibers promoted the
      expression of phenotypic markers of tendon fibroblasts, such as collagen I, III,
      V, and tenomodulin. It is possible that the nanofiber scaffolds of this study
      resemble the matrix in a state of injury, stimulating the cells for matrix
      deposition as part of the repair process, while microfibers represent the healthy
      matrix with micron-sized collagen bundles, thereby inducing cells to maintain the
      fibroblastic phenotype. The results of this study demonstrate that controlling
      the scaffold fiber diameter is critical in the design of scaffolds for functional
      and guided connective tissue repair, and provide new insights into the role of
      matrix parameters in guiding soft tissue healing.

PMID- 23150906
TI  - Independence, institutionalization, death and treatment costs 18 months after
      rehabilitation of older people in two different primary health care settings.
AB  - BACKGROUND: The optimal setting and content of primary health care rehabilitation
      of older people is not known. Our aim was to study independence,
      institutionalization, death and treatment costs 18 months after primary care
      rehabilitation of older people in two different settings. METHODS: Eighteen
      months follow-up of an open, prospective study comparing the outcome of multi
      disciplinary rehabilitation of older people, in a structured and intensive
      Primary care dedicated inpatient rehabilitation (PCDIR, n=202) versus a less
      structured and less intensive Primary care nursing home rehabilitation (PCNHR,
      n=100). PARTICIPANTS: 302 patients, disabled from stroke, hip-fracture,
      osteoarthritis and other chronic diseases, aged >=65years, assessed to have a
      rehabilitation potential and being referred from general hospital or own
      residence. OUTCOME MEASURES: Primary: Independence, assessed by Sunnaas ADL
      Index(SI). Secondary: Hospital and short-term nursing home length of stay (LOS);
      institutionalization, measured by institutional residence rate; death; and costs
      of rehabilitation and care. Statistical tests: T-tests, Correlation tests,
      Pearson's chi2, ANCOVA, Regression and Kaplan-Meier analyses. RESULTS: Overall SI
      scores were 26.1 (SD 7.2) compared to 27.0 (SD 5.7) at the end of rehabilitation,
      a statistically, but not clinically significant reduction (p=0.003 95%CI(0.3
      1.5)). The PCDIR patients scored 2.2points higher in SI than the PCNHR patients,
      adjusted for age, gender, baseline MMSE and SI scores (p=0.003, 95%CI(0.8-3.7)).
      Out of 49 patients staying >28 days in short-term nursing homes, PCNHR-patients
      stayed significantly longer than PCDIR-patients (mean difference 104.9 days,
      95%CI(0.28-209.6), p=0.05). The institutionalization increased in PCNHR (from 12%
      28%, p=0.001), but not in PCDIR (from 16.9%-19.3%, p= 0.45). The overall one year
      mortality rate was 9.6%. Average costs were substantially higher for PCNHR versus
      PCDIR. The difference per patient was 3528? for rehabilitation (p<0.001,
      95%CI(2455-4756)), and 10134? for the at-home care (p=0.002, 95%CI(4066-16202)).
      The total costs of rehabilitation and care were 18702? (=1.6 times) higher for
      PCNHR than for PCDIR. CONCLUSIONS: At 18 months follow-up the PCDIR-patients
      maintained higher levels of independence, spent fewer days in short-term nursing
      homes, and did not increase the institutionalization compared to PCNHR. The costs
      of rehabilitation and care were substantially lower for PCDIR. More communities
      should consider adopting the PCDIR model. TRIAL REGISTRATION: Clinicaltrials.gov
      ID NCT01457300.

PMID- 23150907
TI  - Beyond race-related disparities: is myelodysplastic syndrome the same everywhere?

PMID- 23150909
TI  - A study of the occurrence of symptons of disease of the temporomandibular joint
      masticatory musculature and related structures.
AB  - An examination of the temporomandibular joints, masticatory musculature and
      related structures was made on 1069 persons working in a ship-building yard in
      the south of Sweden. One-fifth of the persons reported that they had frequent
      headache and one-fourth of the persons reported TMJ-sounds. Clinical examination
      of the temporomandibular joints and masticatory musculature showed that clicking
      of the TMJ was the most common symptom (65%) followed by tenderness of the
      masticatory musculature to palpation (37%) and tenderness of the
      temporomandibular joint (10%). Thirty per cent of the persons examined reported
      two or more of these symptoms. Severe abrasion was noted in 12%. The results of
      the investigation suggested that the frequency of diseases related to function of
      the masticatory system is high. It was estimated that some 25-30% of the persons
      examined were in need of treatment.

PMID- 23150910
TI  - Tooth preparation for full coverage-basic principles and rationalized clinical
      procedures.
AB  - The basic principles of tooth preparation for full coverage are discussed and an
      efficient method is described for the operative procedure. The purpose of each of
      the four stages in this technique and of the five different diamond instruments
      which are used in their performance, is discussed. Modifications of the procedure
      are given for posterior and anterior teeth as well as for teeth with periodontal
      involvement. Comparing the relative merit of different types of finishing lines,
      the chamfer type was found most suitable for the majority of preparations.

PMID- 23150908
TI  - Variant of TREM2 associated with the risk of Alzheimer's disease.
AB  - BACKGROUND: Sequence variants, including the epsilon4 allele of apolipoprotein E,
      have been associated with the risk of the common late-onset form of Alzheimer's
      disease. Few rare variants affecting the risk of late-onset Alzheimer's disease
      have been found. METHODS: We obtained the genome sequences of 2261 Icelanders and
      identified sequence variants that were likely to affect protein function. We
      imputed these variants into the genomes of patients with Alzheimer's disease and
      control participants and then tested for an association with Alzheimer's disease.
      We performed replication tests using case-control series from the United States,
      Norway, The Netherlands, and Germany. We also tested for a genetic association
      with cognitive function in a population of unaffected elderly persons. RESULTS: A
      rare missense mutation (rs75932628-T) in the gene encoding the triggering
      receptor expressed on myeloid cells 2 (TREM2), which was predicted to result in
      an R47H substitution, was found to confer a significant risk of Alzheimer's
      disease in Iceland (odds ratio, 2.92; 95% confidence interval [CI], 2.09 to 4.09;
      P=3.42*10(-10)). The mutation had a frequency of 0.46% in controls 85 years of
      age or older. We observed the association in additional sample sets (odds ratio,
      2.90; 95% CI, 2.16 to 3.91; P=2.1*10(-12) in combined discovery and replication
      samples). We also found that carriers of rs75932628-T between the ages of 80 and
      100 years without Alzheimer's disease had poorer cognitive function than
      noncarriers (P=0.003). CONCLUSIONS: Our findings strongly implicate variant TREM2
      in the pathogenesis of Alzheimer's disease. Given the reported antiinflammatory
      role of TREM2 in the brain, the R47H substitution may lead to an increased
      predisposition to Alzheimer's disease through impaired containment of
      inflammatory processes. (Funded by the National Institute on Aging and others.).

PMID- 23150911
TI  - A method of determining the tensile bond strength of fissure sealant materials.
AB  - A simple and reliable method for the determination of the tensile bond strength
      of sealant materials to enamel is described. Using this method, the tensile bond
      strength of Nuva Seal to enamel after 7 days in water at 37( degrees ) C was
      found to be 36.6+/-9.0 kg/cm(2)  with a coefficient of variation of 24.5%. This
      method would be useful for screening of new and modified sealant materials and
      the evaluation of new application procedures to ensure an adequate tensile bond
      strength for clinical use. A tensile bond strength in the range 26-36 kg/cm(2) 
      could be used as the base line value for comparison of new materials and
      procedures involving fissure sealants.

PMID- 23150912
TI  - Masticatory function-a review of the literature: (II) Speed of movement of the
      mandible, rate of chewing and forces developed in chewing.

PMID- 23150913
TI  - Cleanser solution effects on denture base resins: Electronmicroscopic
      investigation.
AB  - Scanning electron microscopic investigations were conducted to determine
      morphostructural alterations on denture base resin surfaces after immersions in
      commercially available oxygen liberating denture cleansers. The topography of
      properly processed denture resins did not show corrosive effects, whereas
      inconsistent surface characteristics of improperly processed wet-mix acrylates
      could suggest less resistance. In spite of thorough rinsing after immersion,
      deposits were noted on the resins of varying amount, size, and quality according
      to the cleanser used. A possible clinical relevance of such deposits is yet to be
      evaluated.

PMID- 23150914
TI  - Elastic tissue in the temporomandibular disc of miniature swine.
AB  - Six intraarticular discs from the temporomandibular joints of three miniature
      swine were examined for the distribution and orientation of elastic fibres.
      Elastic tissue was abundant in the posterior portion of the disc, less tissue was
      seen anteriorly and marginally and the least amount in the central portion.

PMID- 23150915
TI  - Some properties of dental ceramics.
AB  - The rather exacting aesthetic requirements of dental restorations has largely
      dictated the composition of dental ceramic materials. The so-called dental
      porcelains have evolved from the traditional whiteware formula of feldspar, clay
      and quartz. One of the first variables which might be considered is that of
      chemical composition. It is, however, generally accepted that for ceramic
      materials small variations in composition are not critical. Since the early work
      of Watts in 1918, little interest has been expressed in the chemical composition
      of dental porcelain. The composition of traditional dental porcelains has evolved
      over a period of many years by practical trial and error, as discussed by Jones
      (1971). The development of dental porcelains advanced to the point where any
      major improvements in physical properties could only be achieved by major changes
      in composition and technique as advocated by McLean & Hughes (1965). The
      resulting alumina/glass composites which have been developed use a technique
      which involves the build up of an inner core which contains a high proportion of
      crystalline alumina (45-50 %) embedded in a glass matrix surrounded by a
      transparent outer veneer. This work compares the effect of such inter-related
      variables as composition, inclusion of filler, viscosity, texture, hardness, and
      strength of the fired product.

PMID- 23150916
TI  - Bite force in patients with functional disturbances of the masticatory system.
AB  - In thirty patients (24 women and 6 men) treated because of dysfunction of the
      masticatory system at the department of Stomatognathic Physiology, University of
      Gothenburg, bite force was registered before, during and after treatment had been
      completed. In the controls, thirty-six dental students and trainee dental nurses,
      with no dysfunction of the masticatory system, bite force was registered on two
      occasions. Bite force was measured between the first molars on each side and
      between the central incisors. Also finger force was registered. The force
      measurements were made at five different levels, increasing from very weak to
      maximum force. Repeated tests of bite force in the control group, made at
      intervals of about 1 week, gave almost identical results. Bite force in the
      patient group was lower than in the control group at the first registration but
      increased with palliation of the symptoms during treatment. There was no
      significant difference in bite force between the affected and the unaffected
      side.

PMID- 23150917
TI  - A two-year clinical study comparing the effect of dentifrices on selected dental
      materials.
AB  - 1 A two-year double-blind human clinical study has been conducted to determine
      the comparative effect of two commercially available dentifrices on selected
      dental materials. 2 Forty-three adult subjects were selected to participate. They
      received either acrylic resin or silicate restorations in their anterior teeth,
      or a full cast gold veneer crown with an acrylic surface. 3 The subjects were
      randomly assigned to either one of the two dentifrices and utilized the
      dentifrice in their normal manner at least 3 times per day. 4 The dental
      restorations were clinically evaluated in reference to their surface
      characteristics immediately after placement, and after 3, 6, 12 and 24 months'
      use of the dentifrices. The acrylic surfaces of the veneer crowns were also
      evaluated at these same time periods; however, in this case an in vivo tooth
      surface reflectance measurement technique was also utilized. 5 The results of
      this clinical study provide the following conclusion after 24 months use of the
      two dentifrices: There was no difference between the two dentifrices in that
      neither dentifrice produced any abnormal or unusual effect on the surface
      characteristics of either the acrylic or silicate anterior restorations, or the
      acrylic surfaces of the veneer crowns.

PMID- 23150918
TI  - Identification of patients with painful diabetic peripheral neuropathy who have a
      favorable cost profile with pregabalin treatment.
AB  - OBJECTIVE: To characterize patient populations with favorable costs after the
      initiation of pregabalin for the treatment of painful diabetic peripheral
      neuropathy (pDPN) relative to duloxetine, gabapentin, and amitriptyline. METHODS:
      Patients were identified from MarketScan having >= 1 claim for pDPN (ICD-9-CM
      codes 250.6 or 357.2) within 60 days of first prescription (index) for
      pregabalin, duloxetine, gabapentin, or amitriptyline in 2008 and continuous
      enrollment 12 months pre- and postindex. Pregabalin patients were propensity
      score-matched to each comparator. Using cutoff values >= 80% proportion of days
      covered (PDC) and >= 65 years for age, pre- to postindex changes in healthcare
      costs were estimated for pregabalin vs. comparators. RESULTS: Of 987 patients
      initiated on pregabalin, 349 matched to duloxetine; 987 to gabapentin; 276 to
      amitriptyline. The pre- to postindex changes in total healthcare costs were
      similar between cohorts: $3272 with pregabalin vs. $2290 with duloxetine (P =
      0.5280); $3687 with pregabalin vs. $5498 with amitriptyline (P = 0.5863); $3869
      with pregabalin vs. $4106 with gabapentin (P = 0.8303). For the high-age/high-PDC
      population, the pre- to postindex differences in mean total costs were
      significantly lower with pregabalin (P < 0.001) relative to comparators ($3573
      vs. $8288 for duloxetine; $1423 vs. $3167 for gabapentin; $2285 vs. $6160 for
      amitriptyline). CONCLUSIONS: The association of lower total costs among older
      individuals with pDPN who maintain high adherence to pregabalin therapy relative
      to key comparators suggests a pharmacoeconomic advantage of pregabalin in this
      population combined with a need for strategies promoting adherence.

PMID- 23150919
TI  - Phase I/II trial assessing bendamustine plus bortezomib combination therapy for
      the treatment of patients with relapsed or refractory multiple myeloma.
AB  - Bendamustine, active in multiple myeloma (MM), is a bifunctional mechlorethamine
      derivative with alkylating properties. Bortezomib, approved to treat MM, is
      effective in combination with alkylators. The tolerability and efficacy of
      bendamustine plus bortezomib in relapsed/refractory MM was assessed in an open
      label, dose-escalating, phase I/II study. Patients aged >=18 years received
      intravenous bendamustine 50, 70, or 90 mg/m(2)  (days 1 and 4) plus bortezomib
      1.0 mg/m(2)  (days 1, 4, 8, and 11) for up to eight 28-day cycles. No dose
      limiting toxicity was observed after cycle 1; bendamustine 90 mg/m(2)  plus
      bortezomib 1.0 mg/m(2)  was designated the maximum tolerated dose (MTD). The most
      common grade 3/4 adverse events were leucopenia (58%), neutropenia (50%),
      lymphopenia (45%), and thrombocytopenia (30%). Primary efficacy measure was
      overall response rate (ORR), which was the combined complete response (CR), very
      good partial response (VGPR), partial response (PR), and minimal response (MR).
      ORR was 48% (one CR, two VGPR, nine PR, and seven MR) for all 40 enrolled
      patients, 52% (16/31) at the MTD (90 mg/m(2) ), and 42% and 46% for prior use of
      bortezomib (n = 31) or alkylators (n = 28) respectively. Bendamustine plus
      bortezomib was well tolerated with promising efficacy in this heavily pretreated
      population.

PMID- 23150920
TI  - A review on one-dimensional ternary germanate nanomaterials.
AB  - One-dimensional ternary germanate nanomaterials exhibited wide application
      potential in the fields of magnetic devices, photocatalysis, sensors and lithium
      ion batteries owing to their good magnetic, photocatalytic, electrochemical and
      optical properties. The article reviewed the recent progress and patents on one
      dimensional ternary germanate nanomaterials. The recent progress and patents on
      the synthesis of ternary germanate nanowires, nanorods and nanobelts synthesized
      by thermal evaporation, hydrothermal method and chemical vapor deposition process
      were demonstrated. The experimental progress and patents on the application of
      one-dimensional ternary germanate nanomaterials as magnetic devices,
      electrochemical sensors, photocatalysis and lithium ion batteries were discussed
      in detail. Finally, the future development direction of one-dimensional ternary
      germanate nanomaterials for the synthesis and application was also discussed. 

PMID- 23150921
TI  - The kidney and the sympathetic system: a short review.
AB  - Despite the well documented and very effective non pharmacologic and
      pharmacologic therapies, hypertension remains often poorly controlled. There is
      still room for improvements in blood pressure control and recent technological
      advances have generated a regained interest in the physiopathology of renal
      sympathetic innervation in hypertension. In this article we review the evidence
      that renal sympathetic activity is increased in essential hypertension. The
      postganglionic sympathetic fibers are directed to the afferent and efferent renal
      arterioles, the juxtaglomerular apparatus, the proximal renal tubule, the loop of
      Henle, as well as the distal renal tubule and are under the control of many
      reflex loops, which are summarized in a most comprehensive manner for an
      unfamiliar reader within this field of research. Studies on renal denervation
      have provided further insights on the role of the sympathetic system in the
      kidneys, however their proper interpretation requires a special attention to the
      experimental protocols, as is explained in the text. Last, the possibility of
      kidney reinnervation is discussed, as well as the emerging evidence that the
      kidney is also a sensory organ. In summary, this review article provides a strong
      scientific background to understand not only the mechanisms of the hypotensive
      effects, but also those of possible pitfalls, of renal denervation. 

PMID- 23150922
TI  - Kinetic analysis of Arabidopsis glucosyltransferase UGT74B1 illustrates a general
      mechanism by which enzymes can escape product inhibition.
AB  - Plant genomes encode numerous small molecule glycosyltransferases which modulate
      the solubility, activity, immunogenicity and/or reactivity of hormones,
      xenobiotics and natural products. The products of these enzymes can accumulate to
      very high concentrations, yet somehow avoid inhibiting their own biosynthesis.
      Glucosyltransferase UGT74B1 (UDP-glycosyltransferase 74B1) catalyses the
      penultimate step in the core biosynthetic pathway of glucosinolates, a group of
      natural products with important functions in plant defence against pests and
      pathogens. We found that mutation of the highly conserved Ser284 to leucine [wei9
      1 (weak ethylene insensitive)] caused only very mild morphological and metabolic
      phenotypes, in dramatic contrast with knockout mutants, indicating that steady
      state glucosinolate levels are actively regulated even in unchallenged plants.
      Analysis of the effects of the mutation via a structural modelling approach
      indicated that the affected serine interacts directly with UDP-glucose, but also
      predicted alterations in acceptor substrate affinity and the kcat value, sparking
      an interest in the kinetic behaviour of the wild-type enzyme. Initial velocity
      and inhibition studies revealed that UGT74B1 is not inhibited by its glycoside
      product. Together with the effects of the missense mutation, these findings are
      most consistent with a partial rapid equilibrium ordered mechanism. This model
      explains the lack of product inhibition observed both in vitro and in vivo,
      illustrating a general mechanism whereby enzymes can continue to function even at
      very high product/precursor ratios.

PMID- 23150923
TI  - Adverse drug reactions: trends in a tertiary care hospital.
AB  - BACKGROUND: Pharmacovigilance (PV) System is an integral part of drug therapy
      which helps in detection, monitoring and designing strategies to minimize the
      occurrence of adverse drug reaction (ADRs). Present study was planned to study
      the patterns of ADRs in a tertiary care government hospital. METHODS: The present
      study was carried out for a period of one year. Suspected adverse drug reaction
      reports due to medications submitted to the Department of Pharmacology under the
      Pharmacovigilance Programme of India were included. The reports were analyzed for
      their type, severity, organ system involvement, and the causality assessment was
      performed using Naranjo Probability Scale. RESULTS: A total of 520 ADRs were
      received. The highest percentage (66.2%) of ADRs was seen in adult patients.
      Female patients experienced more (57.5%) ADRs. 95% of ADRs occurred in patients
      receiving 5 or more drugs. Medicine department reported the maximum number
      (38.46%) of ADRs. Antimicrobial agents (AMA) (35.7%) were the commonest group of
      drugs causing ADRs. Amongst the organ systems affected, skin constituted a major
      component (40.4%). Causality assessment revealed that 55% of the ADRs were
      possible. Majority of the ADRs were non-serious and only 7 cases were serious and
      required hospitalization. CONCLUSION: The results suggest that healthcare
      professionals (HCP) at this institution are cognizant of PV. However a closer
      liaison between the HCPs and the hospital PV centre, periodic reinforcement of
      the HCPs regarding the need for PV can further improve spontaneous reporting. The
      data will also help in designing strategies for framing policies towards safer
      use of drugs in future.

PMID- 23150924
TI  - The pressure/volume relationship during dobutamine stress echocardiography in
      transplanted heart: comparison with quality of life and coronary anatomy.
AB  - BACKGROUND: Cardiac allograft vasculopathy (CAV) is a major late complication in
      cardiac transplant recipients and has a relevant impact on outcome of these
      patients. AIMS OF THIS STUDY: to compare, in cardiac transplant recipients
      patients, the diagnostic value of pressure/volume relationship (ESPVR) during
      dobutamine stress echocardiography (DSE) for coronary artery disease, assessed by
      Multislice Computed Tomography (MSCT), and by coronary angiography (CA). We also
      analyzed any possible relationship between ESPVR and the Health Related Quality
      of Life of the patients (HRQoL), evaluated by SF-36 questionnaire. METHODS: 25
      consecutive patients underwent DSE within 24 hours after MSCT coronary angiogram
      and then they underwent CA. The HRQoL questionnaire was administered to the
      patients in the settings of DSE. They were followed-up for 6 months. RESULTS: DSE
      has a sensitivity in detecting CAV of 67%, specificity of 95%, positive
      predictive value of 67% and negative predictive value of 95%; DSE with ESPVR has
      a sensitivity of 100%, specificity of 95%, positive predictive value of 75%,
      negative predictive value of 100%; MSCT has a sensitivity of 100%; specificity of
      82%; positive predictive value of 43%; negative predictive value of 100%. Htx
      recipients with a flat-biphasic ESPVR, although asymptomatic, perceived a worst
      HRQoL compared with the up-sloping ESPVR population, and this is statistically
      significant for the general health (p 0.0004), the vitality (p 0.0013) and the
      mental health (p 0.021) SF-36 subscale. CONCLUSIONS: Evaluation with DSE and
      ESPVR is accurate in the clinical control of heart transplant recipients
      reserving invasive evaluation only for patients with abnormal contractility
      indexes.

PMID- 23150925
TI  - The cytological observation of immune adherence of porcine erythrocyte.
AB  - The immune adherence (IA) between the porcine erythrocytes and the opsonized
      Escherichia coli carried green fluorescent protein gene (GFP-E.coli) were
      detected by the fluorescence microscopy, scanning electron microscopy (SEM) and
      transmission electron microscopy (TEM) with an attempt to verify the existence of
      IA between the porcine erythrocytes and complemented-opsonized microbes. Under
      fluorescence microscopy, GFP-E.coli opsonized by fresh rabbit serum complement
      adhered to the erythrocytes and could not be detached by PBS washing, and no IA
      was observed between the erythrocytes and nonopsonized GFP-E.coli after co
      incubation. SEM and TEM also revealed the existence of IA between the serum
      complement-opsonized GFP-E.coli membrane and the erythrocyte membrane. The
      partial complement receptor type 1 (CR1)-like gene from porcine was generated by
      RT-PCR and rapid amplification of cDNA 3' end (3' RACE) (157bp and 578bp), both
      of which have high similarity with published mammal's CR1 gene. The sequences
      were spliced based on homology comparison and submitted to GenBank (GenBank
      Accession No. JX033989). These results indicated that the porcine erythrocytes
      were able to bind to the opsonized microorganisms. Furthermore, the sequencing
      results confirmed that the CR1-like gene exists in porcine.

PMID- 23150927
TI  - Sublingual misoprostol versus standard surgical care for treatment of incomplete
      abortion in five sub-Saharan African countries.
AB  - BACKGROUND: In low-resource settings, where abortion is highly restricted and
      self-induced abortions are common, access to post-abortion care (PAC) services,
      especially treatment of incomplete terminations, is a priority. Standard post
      abortion care has involved surgical intervention but can be hard to access in
      these areas. Misoprostol provides an alternative to surgical intervention that
      could increase access to abortion care. We sought to gather additional evidence
      regarding the efficacy of 400 mcg of sublingual misoprostol vs. standard surgical
      care for treatment of incomplete abortion in the environments where need for
      economical non-surgical treatments may be most useful. METHODS: A total of 860
      women received either sublingual misoprostol or standard surgical care for
      treatment of incomplete abortion in a multi-site randomized trial. Women with
      confirmed incomplete abortion, defined as past or present history of vaginal
      bleeding during pregnancy and an open cervical os, were eligible to participate.
      Participants returned for follow-up one week later to confirm clinical status. If
      abortion was incomplete at that time, women were offered an additional follow-up
      visit or immediate surgical evacuation. RESULTS: Both misoprostol and surgical
      evacuation are highly effective treatments for incomplete abortion (misoprostol:
      94.4%, surgical: 100.0%). Misoprostol treatment resulted in a somewhat lower
      chance of success than standard surgical practice (RR = 0.90; 95% CI: 0.89-0.92).
      Both tolerability of side effects and women's satisfaction were similar in the
      two study arms. CONCLUSION: Misoprostol, much easier to provide than surgery in
      low-resource environments, can be used safely, successfully, and satisfactorily
      for treatment of incomplete abortion. Focus should shift to program
      implementation, including task-shifting the provision of post-abortion care to
      mid- and low- level providers, training and assurance of drug availability. TRIAL
      REGISTRATION: This study has been registered at clinicaltrials.gov as NCT00466999
      and NCT01539408.

PMID- 23150929
TI  - IK6 isoform with associated cytogenetic and molecular abnormalities in Chinese
      patients with Philadelphia chromosome-positive adult acute lymphoblastic
      leukemia.
AB  - The IK6 isoform plays an important role in Philadelphia chromosome-positive adult
      acute lymphoblastic leukemia (Ph + ALL). This study was designed to monitor the
      expression of the IK6 isoform with associated cytogenetic and molecular
      abnormalities. The IK6 isoform, cytogenetic and molecular abnormalities were
      detected in 100 Chinese patients with de novo Ph+ adult ALL. Expression levels of
      the IK6 isoform and BCR-ABL1 transcripts were monitored during treatment. BCR
      ABL1 mutation was identified in 45 paired samples. Strong correlations were found
      between the expression status of the IK6 isoform and blast cells, additional
      cytogenetic abnormalities, BCR-ABL1 transcripts, increased risk of relapse,
      shorter relapse-free survival and overall survival at diagnosis. Higher
      frequencies of single IK6 expression and ABL mutation, including the types and
      shifts thereof, were confirmed in relapsed patients. Furthermore, expression of
      the IK6 isoform was dynamically consistent with BCR-ABL1 transcript levels during
      treatment in the single expression group, whereas no such correlation was
      observed in the co-expression group. The expression pattern of the IK6 isoform
      was altered in three patients from the co-expression group. The findings of this
      study in Chinese patients with Ph+ adult ALL exhibit some discrepancies with data
      reported in other countries, thereby enhancing current knowledge on the
      therapeutic response and prognosis of this disease.

PMID- 23150928
TI  - Characteristics and treatment outcomes of tuberculosis patients who "transfer-in"
      to health facilities in Harare City, Zimbabwe: a descriptive cross-sectional
      study.
AB  - BACKGROUND: Zimbabwe is among the 22 Tuberculosis (TB) high burden countries
      worldwide and runs a well-established, standardized recording and reporting
      system on case finding and treatment outcomes. During TB treatment, patients
      transfer-out and transfer-in to different health facilities, but there are few
      data from any national TB programmes about whether this process happens and if so
      to what extent. The aim of this study therefore was to describe the
      characteristics and outcomes of TB patients that transferred into Harare City
      health department clinics under the national TB programme. Specific objectives
      were to determine i) the proportion of a cohort of TB patients registered as
      transfer-in, ii) the characteristics and treatment outcomes of these transfer-in
      patients and iii) whether their treatment outcomes had been communicated back to
      their respective referral districts after completion of TB treatment. METHODS:
      Data were abstracted from patient files and district TB registers for all
      transfer-in TB patients registered from January to December 2010 within Harare
      City. Descriptive statistics were calculated. RESULTS: Of the 7,742 registered TB
      patients in 2010, 263 (3.5%) had transferred-in: 148 (56%) were males and overall
      median age was 33 years (IQR, 26-40). Most transfer-in patients (74%) came during
      the intensive phase of TB treatment, and 58% were from rural health-facilities.
      Of 176 patients with complete data on the time period between transfer-in and
      transfer-out, only 85 (48%) arrived for registration in Harare from referral
      districts within 1 week of being transferred-out. Transfer-in patients had 69%
      treatment success, but in 21% treatment outcome status was not evaluated.
      Overall, 3/212 (1.4%) transfer-in TB patients had their TB treatment outcomes
      reported back to their referral districts. CONCLUSION: There is need to devise
      better strategies of following up TB patients to their referral Directly Observed
      Treatment (DOT) centres from TB diagnosing centres to ensure that they arrive
      promptly and on time. Recording and reporting of information must improve and
      this can be done through training and supervision. Use of mobile phones and other
      technology to communicate TB treatment outcomes back to the referral districts
      would seem the obvious way to move forward on these issues.

PMID- 23150926
TI  - Protein-hydrogel interactions in tissue engineering: mechanisms and applications.
AB  - Recent advances in our understanding of the sophistication of the cellular
      microenvironment and the dynamics of tissue remodeling during development,
      disease, and regeneration have increased our appreciation of the current
      challenges facing tissue engineering. As this appreciation advances, we are
      better equipped to approach problems in the biology and therapeutics of even more
      complex fields, such as stem cells and cancer. To aid in these studies, as well
      as the established areas of tissue engineering, including cardiovascular,
      musculoskeletal, and neural applications, biomaterials scientists have developed
      an extensive array of materials with specifically designed chemical, mechanical,
      and biological properties. Herein, we highlight an important topic within this
      area of biomaterials research, protein-hydrogel interactions. Due to inherent
      advantages of hydrated scaffolds for soft tissue engineering as well as
      specialized bioactivity of proteins and peptides, this field is well-posed to
      tackle major needs within emerging areas of tissue engineering. We provide an
      overview of the major modes of interactions between hydrogels and proteins (e.g.,
      weak forces, covalent binding, affinity binding), examples of applications within
      growth factor delivery and three-dimensional scaffolds, and finally future
      directions within the area of hydrogel-protein interactions that will advance our
      ability to control the cell-biomaterial interface.

PMID- 23150930
TI  - Functional hamstrings: quadriceps ratios in elite women's soccer players.
AB  - We compared starters and non-starters for various isokinetic strength variables
      in elite women's soccer players. A convenience sample of 10 starters (mean +/- s;
      age = 20 +/- 2 years; height = 170 +/- 4 cm; body mass = 65 +/- 5 kg) and 7 non
      starters (age = 20 +/- 1 years; height = 164 +/- 3 cm; body mass = 63 +/- 4 kg)
      performed maximal voluntary muscle actions of the leg extensors (concentric) and
      flexors (eccentric) on an isokinetic dynamometer in order to measure concentric
      peak torque for the leg extensors, eccentric peak torque for the leg flexors, and
      the functional hamstrings:quadriceps (H:Q) ratio at 1.047 rad . s(-1) and 4.189
      rad . s(-1) concentric peak torque for the leg extensors was not different
      between starters and non-starters. However, it was greater at 1.047 rad . s(-1)
      than at 4.189 rad . s(-1) in both groups. Eccentric peak torque for the leg
      flexors was greater for the starters versus non-starters at 4.189 rad . s(-1).
      Eccentric strength of the leg flexors at fast movement velocities may be used as
      an effective physiological profile and may discriminate between playing status in
      elite women's soccer players.

PMID- 23150931
TI  - Self-reported adherence with the use of a device in a clinical trial as validated
      by electronic monitors: the VIBES study.
AB  - BACKGROUND: Adherences to treatments that require a behavioral action often rely
      on self-reported recall, yet it is vital to determine whether real time self
      reporting of adherence using a simple logbook accurately captures adherence. The
      purpose of this study was to determine whether real time self-reported adherence
      is an accurate measurement of device usage during a clinical trial by comparing
      it to electronic recording. METHODS: Using data collected from older adult men
      and women (N=135, mean age 82.3 yrs; range 66 to 98 yrs) participating in a
      clinical trial evaluating a vibrating platform for the treatment of osteoporosis,
      daily adherence to platform treatment was monitored using both self-reported
      written logs and electronically recorded radio-frequency identification card
      usage, enabling a direct comparison of the two methods over one year. Agreement
      between methods was also evaluated after stratification by age, gender, time in
      study, and cognition status. RESULTS: The two methods were in high agreement
      (overall intraclass correlation coefficient = 0.96). The agreement between the
      two methods did not differ between age groups, sex, time in study and cognitive
      function. CONCLUSIONS: Using a log book to report adherence to a daily
      intervention requiring a behavioral action in older adults is an accurate and
      simple approach to use in clinical trials, as evidenced by the high degree of
      concordance with an electronic monitor.

PMID- 23150932
TI  - Phylogenetic relationships of the glycoprotein gene of bovine ephemeral fever
      virus isolated from mainland China, Taiwan, Japan, Turkey, Israel and Australia.
AB  - BACKGROUND: The glycoprotein (G) gene sequences of bovine ephemeral fever virus
      (BEFV) strains derived from mainland China have not been compared with those of
      the isolates from other countries or areas. Therefore, the G genes of four BEFV
      isolates obtained from mainland China were amplified and sequenced. A
      phylogenetic tree was constructed in order to compare and analyze the genetic
      relationships of the BEFV isolates derived from mainland China and different
      countries and areas. RESULTS: The complete BEFV G gene was successfully amplified
      and sequenced from four isolates that originated from mainland China. A total of
      fifty-one BEFV strains were analyzed based on the G gene sequence and were found
      to be highly conserved. A phylogenetic tree showed that the isolates were grouped
      into three distinct lineages depending on their source of origin. The antigenic
      sites of G1, G2 and G3 are conserved among the isolates, except for several
      substitutions in a few strains. CONCLUSIONS: The phylogenetic relationships of
      the BEFV isolates that originated from mainland China, Taiwan, Japan, Turkey,
      Israel and Australia were closely related to their source of origin, while the
      antigenic sites G1, G2 and G3 are conserved among the BEFV isolates used in this
      work.

PMID- 23150933
TI  - National Essential Medicines List and policy practice: a case study of China's
      health care reform.
AB  - BACKGROUND: In 2009, China implemented the national essential medicines system by
      enacting the National Essential Medicines List 2009. According to the policy of
      this system, primary health care institutions can only stock and use essential
      medicines on the prescribed List. Meanwhile, each province can choose to make its
      own list of supplemented medicines. The goal of the study is to provide
      suggestions for emerging problems and identify future policy-making trends.
      METHODS: In this study, we statistically analyzed the National Essential
      Medicines List 2009 and lists of supplemented medicines of all 29 provinces. We
      also examined the rationality of such medicines based on the DELPHI method and
      literature review, after which we studied the provincial supplements in relation
      to the national essential medicines system. RESULTS: We demonstrated that the
      National Essential Medicines List 2009 provides a comprehensive coverage of
      diseases as well as reasonable varieties of drugs for their treatment. The
      average number of supplemented medicines in 29 provinces is 207, with each
      medicine included in 2.9 provincial lists on average. Only 2.6% supplemented
      medicines are included by more than half of the provinces (>15), indicating great
      regional variance. Among the 32 most frequently supplemented medicines, only 18
      meet the selection principles, including two with strict usage restrictions.
      CONCLUSION: The structure and selection of the National Essential Medicines List
      2009 are relatively reasonable. The main problems, however, include the excessive
      and non-scientific selection of medicines on the supplemented medicines list. The
      function of the provincial lists of supplemented medicines has not been achieved,
      which has influenced the effectiveness of the national essential medicines system
      in China.

PMID- 23150935
TI  - Development of a genetic tool for product regulation in the diverse British pig
      breed market.
AB  - BACKGROUND: The application of DNA markers for the identification of biological
      samples from both human and non-human species is widespread and includes use in
      food authentication. In the food industry the financial incentive to substituting
      the true name of a food product with a higher value alternative is driving food
      fraud. This applies to British pork products where products derived from
      traditional pig breeds are of premium value. The objective of this study was to
      develop a genetic assay for regulatory authentication of traditional pig breed
      labelled products in the porcine food industry in the United Kingdom. RESULTS:
      The dataset comprised of a comprehensive coverage of breed types present in
      Britain: 460 individuals from 7 traditional breeds, 5 commercial purebreds, 1
      imported European breed and 1 imported Asian breed were genotyped using the
      PorcineSNP60 beadchip. Following breed-informative SNP selection, assignment
      power was calculated for increasing SNP panel size. A 96-plex assay created using
      the most informative SNPs revealed remarkably high genetic differentiation
      between the British pig breeds, with an average FST of 0.54 and Bayesian
      clustering analysis also indicated that they were distinct homogenous
      populations. The posterior probability of assignment of any individual of a
      presumed origin actually originating from that breed given an alternative breed
      origin was > 99.5% in 174 out of 182 contrasts, at a test value of log(LR) > 0.
      Validation of the 96-plex assay using independent test samples of known origin
      was successful; a subsequent survey of market samples revealed a high level of
      breed label conformity. CONCLUSION: The newly created 96-plex assay using
      selected markers from the PorcineSNP60 beadchip enables powerful assignment of
      samples to traditional breed origin and can effectively identify mislabelling,
      providing a highly effective tool for DNA analysis in food forensics.

PMID- 23150936
TI  - Evaluation of an assistive technology product design using a paired comparisons
      method within a mixed methods approach: a case study evaluating preferences for
      four types of cutlery with 34 upper limb impaired participants.
AB  - The purpose of the study was the assessment of preferences for four types of
      assistive technology (AT) domestic cutlery with 24 female and 10 male
      participants who had a range of upper limb impairments. A mixed-methods
      methodology, that included a paired comparisons analysis, was used to inform
      product development. Qualitative and quantitative data collected at the time
      provided triangulation of cohort preferences and insight into the reasoning of
      the participants. The results indicate that a high friction surface on AT cutlery
      handles is useful for all upper limb impaired users; however, the unconventional
      shapes of the Caring Cutlery better match the grip patterns generated by those
      with arthritis. Conventionally shaped handles are favoured by those who generate
      conventional grip patterns. Statistical analysis of the paired comparisons
      results indicated a clear preference for the Caring Cutlery by those with
      arthritis. The Etan Cutlery set was favoured by those using one hand that
      predominantly had hemiplegia following a stroke. The paired comparisons method
      was used as part of a mixed methodology that was considered to be cost effective.
      The authors concluded that the methodology was useful to help validate a new
      inclusive/universal product design when the desired attributes are not accurately
      known.

PMID- 23150937
TI  - Lyotropic chiral nematic liquid crystalline aliphatic conjugated polymers based
      on disubstituted polyacetylene derivatives that exhibit high dissymmetry factors
      in circularly polarized luminescence.
AB  - We synthesized disubstituted liquid crystalline polyacetylene (diLCPA)
      derivatives bearing 4-nonyloxy phenyl groups with lyotropic and thermotropic LC
      behavior. The poly(diphenylacetylene) main chain structure of the diLCPAs and the
      chirality induced with either chiral moieties or chiral dopants allow the
      formation of a highly ordered lyotropic N*-LC phase. Circular dichroism (CD)
      spectra of the diLCPAs imply that one-handed intrachain helical structures are
      formed in solution, while interchain helical pi-stacking between the polymer main
      chains are formed in cast film and in the N*-LC state. Absorption dissymmetry
      factors (g(abs)) in the N*-LC state show values on the order of 10(-1). The N*-LC
      state facilitates the formation of helically pi-stacked structures with a high
      degree of helical ordering of the diLCPA and is indispensable for the generation
      of circularly polarized luminescence (CPL) with high emission dissymmetry factors
      (g(em)) on the order of 10(-1). To the best of our knowledge, this is the highest
      reported value of CPL achieved for aliphatic, conjugated polymers. As an
      alternative to the thermotropic N*-LC phase, we have found that the lyotropic N*
      LC phase of diLCPA could be promising materials possessing CPL functionality for
      use in next-generation  pi-conjugated organic optoelectronic devices, displays,
      and sensors.

PMID- 23150938
TI  - Influence of methane in CO2 transport and storage for CCS technology.
AB  - CO(2) Capture and Storage (CCS) is a good strategy to mitigate levels of
      atmospheric greenhouse gases. The type and quantity of impurities influence the
      properties and behavior of the anthropogenic CO(2), and so must be considered in
      the design and operation of CCS technology facilities. Their study is necessary
      for CO(2) transport and storage, and to develop theoretical models for specific
      engineering applications to CCS technology. In this work we determined the
      influence of CH(4), an important impurity of anthropogenic CO(2), within
      different steps of CCS technology: transport, injection, and geological storage.
      For this, we obtained new pressure-density-temperature (PrhoT) and vapor-liquid
      equilibrium (VLE) experimental data for six CO(2) + CH(4) mixtures at
      compositions which represent emissions from the main sources in the European
      Union and United States. The P and T ranges studied are within those estimated
      for CO(2) pipelines and geological storage sites. From these data we evaluated
      the minimal pressures for transport, regarding the density and pipeline's
      capacity requirements, and values for the solubility parameter of the mixtures, a
      factor which governs the solubility of substances present in the reservoir before
      injection. We concluded that the presence of CH(4) reduces the storage capacity
      and increases the buoyancy of the CO(2) plume, which diminishes the efficiency of
      solubility and residual trapping of CO(2), and reduces the injectivity into
      geological formations.

PMID- 23150939
TI  - Normalizing and integrating metabolomics data.
AB  - Metabolomics research often requires the use of multiple analytical platforms,
      batches of samples, and laboratories, any of which can introduce a component of
      unwanted variation. In addition, every experiment is subject to within-platform
      and other experimental variation, which often includes unwanted biological
      variation. Such variation must be removed in order to focus on the biological
      information of interest. We present a broadly applicable method for the removal
      of unwanted variation arising from various sources for the identification of
      differentially abundant metabolites and, hence, for the systematic integration of
      data on the same quantities from different sources. We illustrate the versatility
      and the performance of the approach in four applications, and we show that it has
      several advantages over the existing normalization methods.

PMID- 23150940
TI  - Copper coordination to native N-terminally modified versus full-length amyloid
      beta: second-sphere effects determine the species present at physiological pH.
AB  - Alzheimer's disease is characterized by senile plaques in which metallic ions
      (copper, zinc, and iron) are colocalized with amyloid-beta peptides of different
      sequences in aggregated forms. In addition to the full-length peptides (Abeta1
      40/42), N-terminally truncated Abeta3-40/42 forms and their pyroglutamate
      counterparts, Abetap3-40/42, have been proposed to play key features in the
      aggregation process, leading to the senile plaques. Furthermore, they have been
      shown to be more toxic than the full-length Abeta, which made them central
      targets for therapeutic approaches. In order to better disentangle the possible
      role of metallic ions in the aggregation process, copper(II) coordination to the
      full-length amyloid peptides has been extensively studied in the last years.
      However, regarding the N-terminally modified forms at position 3, very little is
      known. Therefore, copper(I) and copper(II) coordination to those peptides have
      been investigated in the present report using a variety of complementary
      techniques and as a function of  pH. Copper(I) coordination is not affected by
      the N-terminal modifications. In contrast, copper(II) coordination is different
      from that previously reported for the full-length peptide. In the case of the
      pyroglutamate form, this is due to preclusion of N-terminal amine binding. In the
      case of the N-terminally truncated form, alteration in copper(II) coordination is
      caused by second-sphere effects that impact the first binding shell and the pH
      dependent repartition of the various [Cu(peptide)] complexes. Such second-sphere
      effects are anticipated to apply to a variety of metal ions and peptides, and
      their importance on changing the first binding shell has not been fully
      recognized yet.

PMID- 23150934
TI  - TREM2 variants in Alzheimer's disease.
AB  - BACKGROUND: Homozygous loss-of-function mutations in TREM2, encoding the
      triggering receptor expressed on myeloid cells 2 protein, have previously been
      associated with an autosomal recessive form of early-onset dementia. METHODS: We
      used genome, exome, and Sanger sequencing to analyze the genetic variability in
      TREM2 in a series of 1092 patients with Alzheimer's disease and 1107 controls
      (the discovery set). We then performed a meta-analysis on imputed data for the
      TREM2 variant rs75932628 (predicted to cause a R47H substitution) from three
      genomewide association studies of Alzheimer's disease and tested for the
      association of the variant with disease. We genotyped the R47H variant in an
      additional 1887 cases and 4061 controls. We then assayed the expression of TREM2
      across different regions of the human brain and identified genes that are
      differentially expressed in a mouse model of Alzheimer's disease and in control
      mice. RESULTS: We found significantly more variants in exon 2 of TREM2 in
      patients with Alzheimer's disease than in controls in the discovery set (P=0.02).
      There were 22 variant alleles in 1092 patients with Alzheimer's disease and 5
      variant alleles in 1107 controls (P<0.001). The most commonly associated variant,
      rs75932628 (encoding R47H), showed highly significant association with
      Alzheimer's disease (P<0.001). Meta-analysis of rs75932628 genotypes imputed from
      genomewide association studies confirmed this association (P=0.002), as did
      direct genotyping of an additional series of 1887 patients with Alzheimer's
      disease and 4061 controls (P<0.001). Trem2 expression differed between control
      mice and a mouse model of Alzheimer's disease. CONCLUSIONS: Heterozygous rare
      variants in TREM2 are associated with a significant increase in the risk of
      Alzheimer's disease. (Funded by Alzheimer's Research UK and others.).

PMID- 23150943
TI  - Chemical subtleties in small-molecule modulation of peptide receptor function:
      the case of CXCR3 biaryl-type ligands.
AB  - The G protein-coupled chemokine receptor CXCR3 plays a role in numerous
      inflammatory events. The endogenous ligands for the chemokine receptors are
      peptides, but in this study we disclose small-molecule ligands that are able to
      activate CXCR3. A class of biaryl-type compounds that is assembled by convenient
      synthetic routes is described as a new class of CXCR3 agonists. Intriguingly,
      structure-activity relationship and structure-function relationship studies
      reveal that subtle chemical modifications on the outer aryl ring (e.g., either
      the size or position of a halogen atom) result in a full spectrum of agonist
      efficacies on CXCR3. Quantum mechanics calculations and nuclear Overhauser effect
      spectroscopy NMR studies suggest that the biaryl dihedral angle and the
      electronic nature of ortho-substituents play an important role in determining
      agonist efficacies. Compounds 38 (VUF11222) and 39 (VUF11418) are the first
      reported nonpeptidomimetic agonists on CXCR3, rendering them highly useful
      chemical tools for detailed assessment of CXCR3 activation as well as for
      studying downstream CXCR3 signaling.

PMID- 23150942
TI  - Cross-linking mass spectrometry and mutagenesis confirm the functional importance
      of surface interactions between CYP3A4 and holo/apo cytochrome b(5).
AB  - Cytochrome b(5) (cyt b(5)) is one of the key components in the microsomal
      cytochrome P450 monooxygenase system. Consensus has not been reached about the
      underlying mechanism of cyt b(5) modulation of CYP catalysis. Both cyt b(5) and
      apo b(5) are reported to stimulate the activity of several P450 isoforms. In this
      study, the surface interactions of both holo and apo b(5) with CYP3A4 were
      investigated and compared for the first time. Chemical cross-linking coupled with
      mass spectrometric analysis was used to identify the potential electrostatic
      interactions between the protein surfaces. Subsequently, the models of
      interaction of holo/apo b(5) with CYP3A4 were built using the identified
      interacting sites as constraints. Both cyt b(5) and apo b(5) were predicted to
      bind to the same groove on CYP3A4 with close contacts to the B-B' loop of CYP3A4,
      a substrate recognition site. Mutagenesis studies further confirmed that the
      interacting sites on CYP3A4 (Lys96, Lys127, and Lys421) are functionally
      important. Mutation of these residues reduced or abolished cyt b(5) binding
      affinity. The critical role of Arg446 on CYP3A4 in binding to cyt b(5) and/or
      cytochrome P450 reductase was also discovered. The results indicated that
      electrostatic interactions on the interface of the two proteins are functionally
      important. The results indicate that apo b(5) can dock with CYP3A4 in a manner
      analogous to that of holo b(5), so electron transfer from cyt b(5) is not
      required for its effects.

PMID- 23150944
TI  - Difluoro-C4'-oxidized abasic site for efficient amine modification in biological
      systems.
AB  - An oligodeoxynucleotide (ODN) containing a 2',2'-difluorinated analogue of a C4'
      oxidized abasic site (C4'-OAS) was designed for the amine modification of
      biomolecules that interact with nucleic acids. In contrast to the parent C4'-OAS,
      which yielded amine-modified products accompanied by DNA strand scission, the ODN
      containing the difluoro C4'-OAS efficiently yielded products carrying ODNs. The
      amine modification proceeded without additional reagents being required and might
      be applicable to reactions in biological systems.

PMID- 23150945
TI  - Computational modeling and simulation of the Bcl-2 family: paving the way for
      rational drug design.
AB  - Bcl-2 (B-cell lymphoma 2) family proteins have been studied intensively due to
      their association with cancer and other human diseases. These proteins were
      originally associated with the regulation of outer mitochondrial membrane
      integrity and apoptosis. However, there is experimental evidence that suggests
      that several members of this family play instrumental roles in other cellular
      pathways including autophagy, endoplasmic reticulum signaling, mitochondrial
      morphology and synaptic activity among others. Bcl-2 family proteins have been
      explored using diverse experimental and theoretical methods to obtain structural
      information that can provide valuable insight for drug development. This review
      is focused on computational studies related to Bcl-2 family proteins. Different
      strategies are described and evaluated, such as Molecular Dynamics simulations,
      docking, and rational drug design with the aim of demonstrating the importance of
      structural details of either ligands or proteins. The relevance of the knowledge
      obtained using these tools to drug design is discussed.

PMID- 23150946
TI  - Mutations of the apolipoprotein A5 gene with inherited hypertriglyceridaemia:
      review of the current literature.
AB  - Apoliporotein A5 (APOA5), a member of the apolipoprotein family, plays a key
      regulatory role in triglyceride (TG) metabolism. Even though the exact
      biochemical background of its mechanism is not yet fully understood, diseases
      associated with this particular gene highlighted its key role in the metabolism
      of triglycerides in humans. Naturally occurring functional variants of the gene
      and their natural major haplotypes are known to associate with moderately
      elevated triglyceride levels, and are also known to confer risk or protection for
      major polygenic diseases, like coronary heart disease, stroke, or metabolic
      syndrome. On the other hand, case reports and even robust resequencing studies
      verified APOA5 mutations as underlying genetic defects behind extreme
      hypertriglyceridemic phenotype. Soon after the recognition of the first cases,
      there were indications which suggest the existence of less frequent genetic
      variants which, in combination with the common allelic variants of the gene, can
      define haplotypes that are associated with substantial triglyceride level
      increase. In addition, it became evident, that there are rare mutations of the
      APOA5 gene which can be associated with specific complex phenotypes and different
      types of hyperlipoproteinemia, which includes extremely high triglyceride levels
      with multiple organ pathology. These rare mutations may cause inheritable
      hypertriglyceridemia, but they presented at a low frequency and could not be
      captured by standard genotyping array screenings. The identification of new
      mutations still relies on the direct sequencing of APOA5 gene of patients with
      hypertriglyceridemia with an unusual pattern, individually or in huge
      resequencing studies.

PMID- 23150949
TI  - Adherence patterns in patients with type 2 diabetes on basal insulin analogues:
      missed, mistimed and reduced doses.
AB  - OBJECTIVE: To describe basal insulin analogue dosing irregularities, the effect
      of these events on patient functioning, well-being and diabetes management, and
      the identification of patients most at risk. RESEARCH DESIGN AND METHODS: The
      GAPP2 (Global Attitude of Patients and Physicians 2) study was an online
      multinational cross-sectional study of patients with type 2 diabetes currently
      treated with basal insulin, and healthcare professionals (HCPs) involved in the
      care of such patients. Basal insulin adherence patterns were evaluated with
      respect to three types of dosing irregularity: missed, mistimed [+/- 2 hours from
      prescribed time], and reduced dose over the last 30 days. RESULTS: A total of
      3042 patients treated with basal insulin analogues and 1222 prescribers completed
      the full survey; 38% of patients reported any type of basal insulin dosing
      irregularity in the last 30 days. Patients reported missing (22% on 3 +/- 0.16
      occasions), mistiming (24% on 4.2 +/- 0.21 occasions) or reducing (14% on 4.2 +/-
      0.24 occasions) basal insulin doses, with 15% of patients reporting multiple
      types of dosing irregularities. For most patients, missed (83%) and mistimed
      doses (82%) were unintentional, whereas the majority (87%) of patients reducing
      doses did so intentionally. Patients who intentionally missed or reduced a dose
      of basal insulin were significantly more likely to have performed this dosing
      irregularity on multiple occasions. Fifty-three percent of patients increased the
      frequency of blood glucose monitoring, and 17% of patients extended the duration
      of more frequent blood glucose monitoring by one or more days as a result of
      unintentional missed doses. Reduced dosing was highest in a subset of patients
      reporting self-treated hypoglycaemia. CONCLUSIONS: Basal insulin dosing
      irregularities including missed, mistimed and reduced doses are common. A
      significant proportion of patients also report undertaking these irregular dosing
      behaviours at a frequency that would be considered by prescribers to negatively
      impact diabetes management. This is despite the potential under-reporting due to
      recall or social bias that may be a limitation of a self-reported survey around
      these behaviours.

PMID- 23150947
TI  - Single nucleotide polymorphisms and the risk of venous thrombosis: results from a
      Danish case-cohort study.
AB  - A number of single nucleotide polymorphisms (SNP) have been linked to higher risk
      of venous thromboembolism (VTE). We investigated the VTE risk associated with
      SNPs in the GP6 (rs1613662), SERPINC1 (rs2227589), F11 (rs2036914 and rs2289252),
      FGG (rs2066865), and F12 (rs1801020) genes. In F11, the CC genotype for rs2036914
      and the CT and TT genotypes for rs2289252 were associated with a significantly
      higher VTE risk. A trend toward a thrombogenic effect was observed for the risk
      alleles of the GP6 and FGG SNPs. Risk estimates were unaffected by adjustments
      for blood type and F5 rs6025 (Factor V Leiden) mutation.

PMID- 23150948
TI  - Transcriptional regulatory cascades in Runx2-dependent bone development.
AB  - The development of the musculoskeletal system is a complex process that involves
      very precise control of bone formation and growth as well as remodeling during
      postnatal life. Although the understanding of the transcriptional mechanisms of
      osteogenesis has increased considerably, the molecular regulatory basis,
      especially the gene regulatory network of osteogenic differentiation, is still
      poorly understood. This review provides the reader with an overview of the key
      transcription factors that govern bone formation, highlighting their function and
      regulation linked to Runt-related transcription factor 2 (Runx2). Runx2 as the
      master transcription factor of osteoblast differentiation, Twist, Msh homeobox 2
      (Msx2), and promyelocytic leukemia zinc-finger protein (PLZF) acting upstream of
      Runx2, Osterix (Osx) acting downstream of Runx2, and activating transcription
      factor 4 (ATF4) and zinc-finger protein 521 (ZFP521) acting as cofactors of Runx2
      are discussed, and their relevance for tissue engineering is presented.
      References are provided for more in-depth personal study.

PMID- 23150950
TI  - Impact of self-treated hypoglycaemia in type 2 diabetes: a multinational survey
      in patients and physicians.
AB  - OBJECTIVES: The objectives were to estimate the prevalence of self-treated
      hypoglycaemia in patients using basal insulin analogues; identify demographic,
      treatment related and behavioural risk factors; and describe patient and
      physician responses to these events. RESEARCH DESIGN AND METHODS: The GAPP2
      (Global Attitude of Patients and Physicians 2) study was an online multinational
      cross-sectional study of patients with type 2 diabetes currently treated with
      basal insulin, and healthcare professionals involved in the care of such
      patients. The primary variable of interest was self-treated hypoglycaemia within
      the last 30 days. RESULTS: A total of 3042 patients treated with basal insulin
      analogues and 1222 prescribers completed the full survey. Overall, 36% of
      patients had experienced self-treated hypoglycaemia during the previous 30 days.
      In response to self-treated hypoglycaemia, patients reported missing (7%),
      reducing (11%) or mistiming (4%) basal insulin doses, increasing the level of
      glucose monitoring (40%) or utilising healthcare resources (7%). Patients
      reporting irregular basal insulin dosing by missing, mistiming or reducing a dose
      were also significantly more likely to report an episode of self-treated
      hypoglycaemia in the same time period: 41% versus 34% (p = 0.004), 43% versus 33%
      (p < 0.001), and 56% versus 32% (p < 0.001) respectively. Nocturnal events
      worried significantly more patients than diurnal events (42% versus 23%, p <
      0.001). Patient worry about hypoglycaemia, insulin regimen and reduced basal
      dosing were identified as the key differentiating variables associated with
      increased risk of self-treated hypoglycaemic events. Most prescribers (76%)
      believed that insulin analogues minimised the risk of nocturnal hypoglycaemia
      when compared to NPH insulin; 46% also reported being contacted at least once a
      month by insulin analogue patients after self-treated hypoglycaemic events.
      CONCLUSIONS: Self-treated hypoglycaemia is common in approximately one third of
      patients using insulin analogue regimens. Additionally, self-treated
      hypoglycaemia was found to be associated with clinically significant effects on
      patient well-being and functioning, patient and physician management and
      healthcare utilisation despite the potential limitations of an online self
      complete survey such as the need to be topic focused, the potential for under
      reporting and social bias.

PMID- 23150953
TI  - Association between depression, nutritional status, and inflammatory markers in
      peritoneal dialysis patients.
AB  - BACKGROUND: To investigate the relationship between depression, nutritional
      status, and inflammatory markers in patients on peritoneal dialysis (PD).
      PATIENTS AND METHODS: This prospective study included 40 PD patients and 20
      healthy people. The severity of depressive symptoms was assessed using the Beck
      depression inventory, the Hamilton depression rating scale, and the Hamilton
      anxiety rating scale. The depressive patients received antidepressant drug for 8
      weeks. Blood samples were taken before and after antidepressant treatment for the
      high-sensitive C-reactive protein (hs-CRP), interleukin (IL)-1, IL-6, and tumor
      necrosis factor-alpha (TNF-alpha) levels. RESULTS: Ten (25%) of the 40 PD
      patients had depression. No significant difference was determined between
      depressive patients and nondepressive patients. The mean erythrocyte
      sedimentation rate was higher in depressive patients. There was no significant
      difference for other inflammation parameters, including hs-CRP, TNF-alpha, IL-1,
      and IL-6, between depressive patients and nondepressive patients. In the
      depressive patients, we did not observe any significant change in nutritional
      parameters after antidepressant treatment. When we evaluated inflammation
      parameters of the depressive patients before and after antidepressant treatment,
      only IL-1 and IL-6 levels were significantly increased after antidepressant
      treatment. CONCLUSION: The depressive disorder in PD patients is a common
      psychopathology and has no significant effects on nutritional status and
      inflammation.

PMID- 23150952
TI  - Balanced pan-PPAR activator bezafibrate in combination with statin: comprehensive
      lipids control and diabetes prevention?
AB  - All fibrates are peroxisome proliferators-activated receptors (PPARs)-alpha
      agonists with ability to decrease triglyceride and increase high density
      lipoprotein- cholesterol (HDL-C). However, bezafibrate has a unique
      characteristic profile of action since it activates all three PPAR subtypes
      (alpha, gamma and delta) at comparable doses. Therefore, bezafibrate operates as
      a pan-agonist for all three PPAR isoforms. Selective PPAR gamma agonists
      (thiazolidinediones) are used to treat type 2 diabetes mellitus (T2DM). They
      improve insulin sensitivity by up-regulating adipogenesis, decreasing free fatty
      acid levels, and reversing insulin resistance. However, selective PPAR gamma
      agonists also cause water retention, weight gain, peripheral edema, and
      congestive heart failure. The expression of PPAR beta/ delta in essentially all
      cell types and tissues (ubiquitous presence) suggests its potential fundamental
      role in cellular biology. PPAR beta/ delta effects correlated with enhancement of
      fatty acid oxidation, energy consumption and adaptive thermogenesis. Together,
      these data implicate PPAR beta/delta in fuel combustion and suggest that pan-PPAR
      agonists that include a component of PPAR beta/delta activation might offset some
      of the weight gain issues seen with selective PPAR gamma agonists, as was
      demonstrated by bezafibrate studies. Suggestively, on the whole body level all
      PPARs acting as one orchestra and balanced pan-PPAR activation seems as an
      especially attractive pharmacological goal. Conceptually, combined PPAR gamma and
      alpha action can target simultaneously insulin resistance and atherogenic
      dyslipidemia, whereas PPAR beta/delta properties may prevent the development of
      overweight. Bezafibrate, as all fibrates, significantly reduced plasma
      triglycerides and increased HDL-C level (but considerably stronger than other
      major fibrates). Bezafibrate significantly decreased prevalence of small, dense
      low density lipoproteins particles, remnants, induced atherosclerotic plaque
      regression in thoracic and abdominal aorta and improved endothelial function. In
      addition, bezafibrate has important fibrinogen-related properties and anti
      inflammatory effects. In clinical trials bezafibrate was highly effective for
      cardiovascular risk reduction in patients with metabolic syndrome and atherogenic
      dyslipidemia. The principal differences between bezafibrate and other fibrates
      are related to effects on glucose level and insulin resistance. Bezafibrate
      decreases blood glucose level, HbA1C, insulin resistance and reduces the
      incidence of T2DM compared to placebo or other fibrates. Currently statins are
      the cornerstone of the treatment and prevention of cardiovascular diseases
      related to atherosclerosis. However, despite the increasing use of statins as
      monotherapy for low density lipoprotein- cholesterol (LDL-C) reduction, a
      significant residual cardiovascular risk is still presented in patients with
      atherogenic dyslipidemia and insulin resistance, which is typical for T2DM and
      metabolic syndrome. Recently, concerns were raised regarding the development of
      diabetes in statin-treated patients. Combined bezafibrate/statin therapy is more
      effective in achieving a comprehensive lipid control and residual cardiovascular
      risk reduction. Based on the beneficial effects of pan-PPAR agonist bezafibrate
      on glucose metabolism and prevention of new-onset diabetes, one could expect a
      neutralization of the adverse pro-diabetic effect of statins using the strategy
      of a combined statin/fibrate therapy.

PMID- 23150955
TI  - Lessons learned preparing for Medicare bundled payments.

PMID- 23150954
TI  - In silico biosynthesis of virenose, a methylated deoxy-sugar unique to Coxiella
      burnetii lipopolysaccharide.
AB  - BACKGROUND: Coxiella burnetii is Gram-negative bacterium responsible for the
      zoonosis Q-fever. While it has an obligate intracellular growth habit, it is able
      to persist for extended periods outside of a host cell and can resist
      environmental conditions that would be lethal to most prokaryotes. It is these
      extracellular bacteria that are the infectious stage encountered by eukaryotic
      hosts. The intracellular form has evolved to grow and replicate within acidified
      parasitophorous vacuoles. The outer coat of C. burnetii comprises a complex
      lipopolysaccharide (LPS) component that includes the unique methylated-6
      deoxyhexose, virenose. Although potentially important as a biomarker for C.
      burnetii, the pathway for its biosynthesis remains obscure. RESULTS: The 6
      deoxyhexoses constitute a large family integral to the LPS of many eubacteria. It
      is believed that precursors of the methylated-deoxyhexoses traverse common early
      biosynthetic steps as nucleotide-monosaccharides. As a prelude to a full
      biosynthetic characterization, we present herein the results from bioinformatics
      based, proteomics-supported predictions of the pathway for virenose synthesis.
      Alternative possibilities are considered which include both GDP-mannose and TDP
      glucose as precursors. CONCLUSION: We propose that biosynthesis of the unique C.
      burnetii biomarker, virenose, involves an early pathway similar to that of other
      C-3'-methylated deoxysugars which then diverges depending upon the nucleotide
      carrier involved. The alternatives yield either the D- or L-enantiomers of
      virenose. Both pathways require five enzymatic steps, beginning with either
      glucose-6-phosphate or mannose-6-phosphate. Our in silico results comprise a
      model for virenose biosynthesis that can be directly tested. Definition of this
      pathway should facilitate the development of therapeutic agents useful for
      treatment of Q fever, as well as allowing improvements in the methods for
      diagnosing this highly infectious disease.

PMID- 23150956
TI  - Reducing administrative costs and improving the health care system.

PMID- 23150957
TI  - The reciprocity of recognition--what medicine exposes about self and other.

PMID- 23150958
TI  - Differentiation of reinfection from relapse in recurrent Lyme disease.
AB  - BACKGROUND: Erythema migrans is the most common manifestation of Lyme disease.
      Recurrences are not uncommon, and although they are usually attributed to
      reinfection rather than relapse of the original infection, this remains somewhat
      controversial. We used molecular typing of Borrelia burgdorferi isolates obtained
      from patients with culture-confirmed episodes of erythema migrans to distinguish
      between relapse and reinfection. METHODS: We determined the genotype of the gene
      encoding outer-surface protein C (ospC) of B. burgdorferi strains detected in
      cultures of skin or blood specimens obtained from patients with consecutive
      episodes of erythema migrans. After polymerase-chain-reaction amplification, ospC
      genotyping was performed by means of reverse line-blot analysis or DNA sequencing
      of the nearly full-length gene. Most strains were further analyzed by determining
      the genotype according to the 16S-23S ribosomal RNA intergenic spacer type,
      multilocus sequence typing, or both. Patients received standard courses of
      antibiotics for erythema migrans. RESULTS: B. burgdorferi isolates obtained from
      17 patients who received a diagnosis of erythema migrans between 1991 and 2011
      and who had 22 paired episodes of this lesion (initial and second episodes) were
      available for testing. The ospC genotype was found to be different at each
      initial and second episode. Apparently identical genotypes were identified on
      more than one occasion in only one patient, at the first and third episodes, 5
      years apart, but different genotypes were identified at the second and fourth
      episodes. CONCLUSIONS: None of the 22 paired consecutive episodes of erythema
      migrans were associated with the same strain of B. burgdorferi on culture. Our
      data show that repeat episodes of erythema migrans in appropriately treated
      patients were due to reinfection and not relapse. (Funded by the National
      Institutes of Health and the William and Sylvia Silberstein Foundation.).

PMID- 23150960
TI  - Accidental hypothermia.

PMID- 23150959
TI  - Trends in survival after in-hospital cardiac arrest.
AB  - BACKGROUND: Despite advances in resuscitation care in recent years, it is not
      clear whether survival and neurologic function after in-hospital cardiac arrest
      have improved over time. METHODS: We identified all adults who had an in-hospital
      cardiac arrest at 374 hospitals in the Get with the Guidelines-Resuscitation
      registry between 2000 and 2009. Using multivariable regression, we examined
      temporal trends in risk-adjusted rates of survival to discharge. Additional
      analyses explored whether trends were due to improved survival during acute
      resuscitation or postresuscitation care and whether they occurred at the expense
      of greater neurologic disability in survivors. RESULTS: Among 84,625 hospitalized
      patients with cardiac arrest, 79.3% had an initial rhythm of asystole or
      pulseless electrical activity, and 20.7% had ventricular fibrillation or
      pulseless ventricular tachycardia. The proportion of cardiac arrests due to
      asystole or pulseless electrical activity increased over time (P<0.001 for
      trend). Risk-adjusted rates of survival to discharge increased from 13.7% in 2000
      to 22.3% in 2009 (adjusted rate ratio per year, 1.04; 95% confidence interval
      [CI], 1.03 to 1.06; P<0.001 for trend). Survival improvement was similar in the
      two rhythm groups and was due to improvement in both acute resuscitation survival
      and postresuscitation survival. Rates of clinically significant neurologic
      disability among survivors decreased over time, with a risk-adjusted rate of
      32.9% in 2000 and 28.1% in 2009 (adjusted rate ratio per year, 0.98; 95% CI, 0.97
      to 1.00; P=0.02 for trend). CONCLUSIONS: Both survival and neurologic outcomes
      after in-hospital cardiac arrest have improved during the past decade at
      hospitals participating in a large national quality-improvement registry. (Funded
      by the American Heart Association.).

PMID- 23150961
TI  - Images in clinical medicine. Thoracolumbar fracture with preservation of
      neurologic function.

PMID- 23150962
TI  - Case records of the Massachusetts General Hospital. Case 35-2012. A 69-year-old
      chronically ill man with weakness, anorexia, and diffuse pain.

PMID- 23150963
TI  - Reinfection versus relapse in Lyme disease.

PMID- 23150964
TI  - From clinical observation to mechanism--Heyde's syndrome.

PMID- 23150966
TI  - Thyroid nodules with indeterminate cytology.

PMID- 23150967
TI  - Thyroid nodules with indeterminate cytology.

PMID- 23150968
TI  - Thyroid nodules with indeterminate cytology.

PMID- 23150970
TI  - Tofacitinib in active ulcerative colitis.

PMID- 23150971
TI  - Tofacitinib in active ulcerative colitis.

PMID- 23150973
TI  - Effect of HIV-2 infection on HIV-1 disease progression.

PMID- 23150974
TI  - Effect of HIV-2 infection on HIV-1 disease progression.

PMID- 23150975
TI  - Effect of HIV-2 infection on HIV-1 disease progression.

PMID- 23150977
TI  - Patient access to medical devices.

PMID- 23150978
TI  - Patient access to medical devices.

PMID- 23150979
TI  - Images in clinical medicine. Hemolytic anemia after mitral-valve repair.

PMID- 23150980
TI  - Feasibility of evidence-based diagnosis and management of heart failure in older
      people in care: a pilot randomised controlled trial.
AB  - BACKGROUND: Many older people in long-term care do not receive evidence-based
      diagnosis or management for heart failure; it is not known whether this can be
      achieved for this population. We initiated an onsite heart failure service,
      compared with 'usual care' with the aim of establishing the feasibility of
      accurate diagnosis and appropriate management. METHODS: A pilot randomised
      controlled trial which randomised residents from 33 care facilities in North-East
      England with left ventricular systolic dysfunction (LVSD) to usual care or an
      onsite heart failure service. The primary outcome was the optimum prescription of
      angiotensin-converting enzyme inhibitors and beta-adrenergic antagonists at 6
      months. RESULTS: Of 399 echocardiographically-screened residents aged 65-100
      years, 30 subjects with LVSD were eligible; 28 (93%) consented and were
      randomised (HF service: 16; routine care: 12). Groups were similar at baseline;
      six month follow-up was completed for 25 patients (89%); 3 (11%) patients died.
      Results for the primary outcome were not statistically significant but there was
      a consistent pattern of increased drug use and titration to optimum dose in the
      intervention group (21% compared to 0% receiving routine care, p=0.250).
      Hospitalisation rates, quality of life and mortality at 6 months were similar
      between groups. CONCLUSIONS: This study demonstrated the feasibility of an on
      site heart failure service for older long-term care populations. Optimisation of
      medication appeared possible without adversely affecting quality of life; this
      questions clinicians' concerns about adverse effects in this group. This has
      international implications for managing such patients. These methods should be
      replicated in a large-scale study to quantify the scale of benefit. TRIAL
      REGISTRATION: ISRCTN19781227 http://www.controlled-trials.com/ISRCTN19781227

PMID- 23150981
TI  - Higher lipocalin 2 expression may represent an independent favorable prognostic
      factor in cytogenetically normal acute myeloid leukemia.
AB  - Abstract Several molecular markers, such as NPM1, FLT3 and CEBPA, have been
      incorporated into both the World Health Organization and European LeukemiaNet
      classifications as routine assessments for the diagnosis and evaluation of
      prognostic significance in acute myeloid leukemia (AML). Lipocalin 2 (LCN2) is
      related to cancer development and is believed to be associated with the outcome
      of cytogenetically normal (CN)-AML. In the present study, we analyzed the
      prognostic effects and interactions of LCN2 expression (by molecular analysis,
      quantitative real-time polymerase chain reaction [qRT-PCR]) with neucleophosmin
      1, fms-related tyrosine kinase 3 (FLT3) and CCAAT/enhancer-binding protein alpha
      mutations in 85 patients with CN-AML receiving intensive induction chemotherapy.
      Our results indicate that patients with higher LCN2 mRNA expression in the bone
      marrow (LCN2high), especially in combination with wild type FLT3-ITD, had better
      prognoses. FLT3-ITD compensated LCN2-overexpression-enhanced oxidative stress
      induced apoptosis in cell line studies. In conclusion, LCN2high was associated
      with better prognosis, and FLT3 status had an adjuvant effect on overall
      survival. 

PMID- 23150983
TI  - Synthesis and antitubercular activity of 2-(substituted phenyl/benzyl-amino)-6-(4
      chlorophenyl)-5-(methoxycarbonyl)-4-methyl-3,6-dihydropyrimidin-1-ium chlorides.
AB  - A series of 2-(substituted phenyl/benzyl-amino)-6-(4-chlorophenyl)-5
      (methoxycarbonyl)-4-methyl-3,6-dihydropyrimidin-1-ium chlorides 7-13 and 15 was
      synthesized in their hydrochloride salt form. The title compounds were
      characterized by FT-IR, NMR ((1)H and (13)C) and elemental analysis. They were
      evaluated for their in vitro antitubercular activity against Mycobacterium
      tuberculosis H37Rv, multidrug resistance tuberculosis and extensively drug
      resistance tuberculosis by agar diffusion method and tested for the cytotoxic
      action on peripheral blood mononuclear cells by MTT assay. Among all the tested
      compounds in the series, compounds 7 and 11 emerged as promising antitubercular
      agents at 16 MUg/mL against multidrug resistance tuberculosis and over 64 MUg/mL
      against extensively drug resistance tuberculosis. The conformational features and
      supramolecular assembly of the promising compounds 7 and 11 were determined by
      single crystal X-ray study.

PMID- 23150982
TI  - Stochastic amplitude-modulated stretching of rabbit flexor digitorum profundus
      tendons reduces stiffness compared to cyclic loading but does not affect tenocyte
      metabolism.
AB  - BACKGROUND: It has been demonstrated that frequency modulation of loading
      influences cellular response and metabolism in 3D tissues such as cartilage, bone
      and intervertebral disc. However, the mechano-sensitivity of cells in linear
      tissues such as tendons or ligaments might be more sensitive to changes in strain
      amplitude than frequency. Here, we hypothesized that tenocytes in situ are
      mechano-responsive to random amplitude modulation of strain. METHODS: We compared
      stochastic amplitude-modulated versus sinusoidal cyclic stretching. Rabbit tendon
      were kept in tissue-culture medium for twelve days and were loaded for 1h/day for
      six of the total twelve culture days. The tendons were randomly subjected to one
      of three different loading regimes: i) stochastic (2 - 7% random strain
      amplitudes), ii) cyclic_RMS (2-4.42% strain) and iii) cyclic_high (2 - 7%
      strain), all at 1 Hz and for 3,600 cycles, and one unloaded control. RESULTS: At
      the end of the culture period, the stiffness of the "stochastic" group was
      significantly lower than that of the cyclic_RMS and cyclic_high groups (both, p <
      0.0001). Gene expression of eleven anabolic, catabolic and inflammatory genes
      revealed no significant differences between the loading groups. CONCLUSIONS: We
      conclude that, despite an equivalent metabolic response, stochastically stretched
      tendons suffer most likely from increased mechanical microdamage, relative to
      cyclically loaded ones, which is relevant for tendon regeneration therapies in
      clinical practice.

PMID- 23150984
TI  - Hetero-multinuclear ruthenium(III)/platinum(II) complexes that potentially
      exhibit both antimetastatic and antineoplastic properties.
AB  - Hetero-multinuclear, platinum/ruthenium species were synthesized and tested for
      their effect on the motility of A549 (nonsmall cell lung) and MDA-MB-231 (breast)
      cancer cells and for their ability to inhibit DNA mobility using gel
      electrophoresis. It was found that the Ru(2)Pt trinuclear species
      [Na(2)]{[Ru(III)Cl(4)(DMSO-S)(-MU-pyz)](2)Pt(II)Cl(2)}, AH197, was much more
      efficient at inhibiting cell motility than [C(3)N(2)H(5)][Ru(III)Cl(4)(DMSO
      S)(C(3)N(2)H(4))], NAMI-A, while the dinuclear RuPt species [K][Ru(III)Cl(4)(DMSO
      S)(-MU-pyz)Pt(II)(DMSO-S)Cl(2)], IT127, was slightly better than NAMI-A. However,
      the dinuclear species retarded the electrophoretic mobility of DNA greater than
      both the trinuclear complex and cisplatin. The metal complexes and their
      respective BSA protein/metal adducts were studied by X-ray absorption
      spectroscopy. The spectra led to the conclusion that BSA donor atoms have
      substituted for the chloride ligands and perhaps the DMSO ligands.

PMID- 23150985
TI  - One substrate, five products: reactions catalyzed by the dihydroneopterin
      aldolase from Mycobacterium tuberculosis.
AB  - Tetrahydrofolate cofactors are required for one carbon transfer reaction involved
      in the synthesis of purines, amino acids, and thymidine. Inhibition of
      tetrahydrofolate biosynthesis is a powerful therapeutic strategy in the treatment
      of several diseases, and the possibility of using antifolates to inhibit enzymes
      from  Mycobacterium tuberculosis  has been explored. This work focuses on the
      study of the first enzyme in tetrahydrofolate biosynthesis that is unique to
      bacteria, dihydroneopterin aldolase (MtDHNA). This enzyme requires no metals or
      cofactors and does not form a protein-mediated Schiff base with the substrate,
      unlike most aldolases. Here, we were able to demonstrate that the reaction
      catalyzed by MtDHNA generates three different pterin products, one of which is
      not produced by other wild-type DHNAs. The enzyme-substrate complex partitions
      51% in the first turnover to form the aldolase products, 24% to the epimerase
      product and 25% to the oxygenase products. The aldolase reaction is strongly pH
      dependent, and apparent pK(a) values were obtained for the first time for this
      class of enzyme. Furthermore, chemistry is rate limiting for the aldolase
      reaction, and the analysis of solvent kinetic isotope effects in steady-state and
      pre-steady-state conditions, combined with proton inventory studies, revealed
      that two protons and a likely solvent contribution are involved in formation and
      breakage of a common intermediate. This study provides information about the
      plasticity required from a catalyst that possesses high substrate specificity
      while being capable of utilizing two distinct epimers with the same efficiency to
      generate five distinct products.

PMID- 23150986
TI  - Structure and glycolipid binding properties of the nematicidal protein Cry5B.
AB  - Crystal (Cry) proteins are globally used in agriculture as proteinaceous
      insecticides. They have also been recently recognized to have great potential as
      anthelmintic agents in targeting parasitic roundworms (e.g., hookworms). The most
      extensively characterized of the anthelmintic Cry proteins is Cry5B. We report
      here the 2.3 A resolution structure of the proteolytically activated form of
      Cry5B. This structure, which is the first for a nematicidal Cry protein, shows
      the familiar three-domain arrangement seen in insecticidal Cry proteins. However,
      domain II is unusual in that it more closely resembles a banana lectin than it
      does other Cry proteins. This result is consistent with the fact that the
      receptor for Cry5B consists of a set of invertebrate-specific glycans (attached
      to lipids) and also suggests that domain II is important for receptor binding. We
      found that not only galactose but also N-acetylgalactosamine (GalNAc) is an
      efficient competitor for binding between Cry5B and glycolipids. GalNAc is one of
      the core arthroseries tetrasaccharides of the Cry5B receptor and galactose an
      antennary sugar that emanates from this core. These and prior data suggest that
      the minimal binding determinant for Cry5B consists of a core GalNAc and two
      antennary galactoses. Lastly, the protoxin form of Cry5B was found to bind
      nematode glycolipids with a specificity equal to that of activated Cry5B, but
      with lower affinity. This suggests that the initial binding of Cry5B protoxin to
      glycolipids can be stabilized at the nematode cell surface by proteolysis. These
      results lay the groundwork for the design of effective Cry5B-based anthelmintics.

PMID- 23150987
TI  - Community-level influences on women's experience of intimate partner violence and
      terminated pregnancy in Nigeria: a multilevel analysis.
AB  - BACKGROUND: Intimate partner violence (IPV) is a major public health problem with
      serious consequences for women's physical, mental, sexual and reproductive
      health. Reproductive health outcomes such as unwanted and terminated pregnancies,
      fetal loss or child loss during infancy, non-use of family planning methods, and
      high fertility are increasingly recognized. However, little is known about the
      role of community influences on women's experience of IPV and its effect on
      terminated pregnancy, given the increased awareness of IPV being a product of
      social context. This study sought to examine the role of community-level norms
      and characteristics in the association between IPV and terminated pregnancy in
      Nigeria. METHODS: Multilevel logistic regression analyses were performed on
      nationally-representative cross-sectional data including 19,226 women aged 15-49
      years in Nigeria. Data were collected by a stratified two-stage sampling
      technique, with 888 primary sampling units (PSUs) selected in the first sampling
      stage, and 7,864 households selected through probability sampling in the second
      sampling stage. RESULTS: Women who had experienced physical IPV, sexual IPV, and
      any IPV were more likely to have terminated a pregnancy compared to women who had
      not experienced these IPV types.IPV types were significantly associated with
      factors reflecting relationship control, relationship inequalities, and socio
      demographic characteristics. Characteristics of the women aggregated at the
      community level (mean education, justifying wife beating, mean age at first
      marriage, and contraceptive use) were significantly associated with IPV types and
      terminated pregnancy. CONCLUSION: Findings indicate the role of community
      influence in the association between IPV-exposure and terminated pregnancy, and
      stress the need for screening women seeking abortions for a history of abuse.

PMID- 23150989
TI  - Comment on "Solubility of CO2, H2S, and their mixture in the ionic liquid 1-octyl
      3-methylimidazolium bis(trifluoromethyl)sulfonylimide".

PMID- 23150988
TI  - Large-scale sequencing based on full-length-enriched cDNA libraries in pigs:
      contribution to annotation of the pig genome draft sequence.
AB  - BACKGROUND: Along with the draft sequencing of the pig genome, which has been
      completed by an international consortium, collection of the nucleotide sequences
      of genes expressed in various tissues and determination of entire cDNA sequences
      are necessary for investigations of gene function. The sequences of expressed
      genes are also useful for genome annotation, which is important for isolating the
      genes responsible for particular traits. RESULTS: We performed a large-scale
      expressed sequence tag (EST) analysis in pigs by using 32 full-length-enriched
      cDNA libraries derived from 28 kinds of tissues and cells, including seven
      tissues (brain, cerebellum, colon, hypothalamus, inguinal lymph node, ovary, and
      spleen) derived from pigs that were cloned from a sow subjected to genome
      sequencing. We obtained more than 330,000 EST reads from the 5'-ends of the cDNA
      clones. Comparison with human and bovine gene catalogs revealed that the ESTs
      corresponded to at least 15,000 genes. cDNA clones representing contigs and
      singlets generated by assembly of the EST reads were subjected to full-length
      determination of inserts. We have finished sequencing 31,079 cDNA clones
      corresponding to more than 12,000 genes. Mapping of the sequences of these cDNA
      clones on the draft sequence of the pig genome has indicated that the clones are
      derived from about 15,000 independent loci on the pig genome. CONCLUSIONS: ESTs
      and cDNA sequences derived from full-length-enriched libraries are valuable for
      annotation of the draft sequence of the pig genome. This information will also
      contribute to the exploration of promoter sequences on the genome and to
      molecular biology-based analyses in pigs.

PMID- 23150991
TI  - Mechanistic study of 17alpha-ethinylestradiol biodegradation by Pleurotus
      ostreatus: tracking of extracelullar and intracelullar degradation mechanisms.
AB  - The white rot fungus Pleurotus ostreatus is able to completely remove the
      synthetic hormone 17alpha-ethinylestradiol (EE2, 200 MUg in 20 mL) from a liquid
      complex or mineral medium in 3 or 14 days, respectively. Its efficiency has also
      been documented in the removal of estrogenic activity that correlated with the
      EE2 degradation. A set of in vitro experiments using various cellular and enzyme
      fractions has been performed and the results showed that EE2 was degraded by
      isolated laccase (about 90% within 24 h). The degradation was also tested with
      concentrated extracellular liquid where degradation reached 50% mainly due to the
      laccase activity; however, after a supplementation with H2O2 and Mn2+, residual
      manganese-dependent peroxidase activities (40 times lower than Lac) raised the
      degradation to 100%. Moreover, the intracellular fraction and also laccase-like
      activity associated with fungal mycelium were found to be efficient in the
      degradation too. Isolated microsomal proteins appeared to also be involved in the
      process. The degradation was completely suppressed in the presence of cytochrome
      P-450 inhibitors, piperonylbutoxide and carbon monoxide, indicating a role of
      this monooxygenase in the degradation process. Attention was also paid to
      monitoring of changes in the estrogenic activity during these particular in vitro
      experiments when mainly degradations related to ligninolytic enzymes were found
      to decrease the estrogenic activity with EE2 removal proportionally. Several
      novel metabolites of EE2 were detected using different chromatographic method
      with mass spectrometric techniques (LC-MS, GC-MS) including also [13C]-labeled
      substrates. The results document the involvement of various different
      simultaneous mechanisms in the EE2 degradation by P. ostreatus by both the
      ligninolytic system and the eukaryotic machinery of cytochromes P-450.

PMID- 23150990
TI  - The effects of age and carbon black on airway resistance in mice.
AB  - CONTEXT: Ambient particulate matter (PM) is associated with acute exacerbations
      of airflow obstruction. Additionally, elderly individuals are more susceptible to
      increased functional morbidity following acute PM exposure. OBJECTIVE: The
      purpose of this study is to determine the aging effects of PM exposure on the
      responsiveness of airway smooth muscle in mice. We hypothesized that airway
      reactivity induced by methacholine (Mch) will increase with age in PM exposed
      mice. MATERIALS AND METHODS: Male C57BL/6 (B6) mice at 11, 39, 67, and 96 weeks
      of age were exposed to carbon black (CB) or room air (RA) for 3 h on 3
      consecutive days. One day after the last exposure, mice were anesthetized and
      airways resistance (R(aw)) was measured by forced oscillation following half-log
      dose increases of aerosolized Mch. RESULTS: Baseline R(aw) was significantly
      lower in 67 and 96 week mice compared to 11-week mice (p < 0.05). In RA exposed
      mice, an age-dependent decline in Mch-induced airway reactivity occurred in
      association with the highest Mch doses at ages 67 and 96 weeks (p < 0.05). A
      significantly (p < 0.05) greater Mch-induced R(aw) response occurred in 67-week
      mice exposed to CB compared with age-matched RA-exposed mice. DISCUSSION AND
      CONCLUSION: Our results show a progressive decrease in the Mch-induced R(aw)
      response with age in mice. The effect of CB exposure resulted in greater airway
      reactivity in middle-aged mice, which highlights the effects of PM exposure on
      the lung as it relates to increased morbidity and mortality with older age.

PMID- 23150993
TI  - Multiplexed evaluation of serum and CSF pharmacokinetics of brain-targeting
      single-domain antibodies using a NanoLC-SRM-ILIS method.
AB  - FC5 and FC44 are single-domain antibodies (VHHs), selected by functional panning
      of phage-display llama VHH library for their ability to internalize human brain
      endothelial cells (BEC) and to transmigrate the in vitro BBB model.
      Quantification of brain delivery of FC5 and FC44 in vivo was challenging using
      classical methods because of their short plasma half-life and their loss of
      functionality with radioactive labeling. A highly sensitive (detection limit <2
      ng/mL) and specific SRM-ILIS method to detect and quantify unlabeled VHHs in
      multiplexed assays was developed and applied to comparatively evaluate brain
      delivery of FC5 and FC44, and two control VHHs, EG2 and A20.1. FC5 and FC44
      compared to control VHHs demonstrated significantly (p < 0.01) enhanced transport
      (50-100-fold) across rat in vitro BBB model as well as in vivo brain targeting
      assessed by optical imaging. The multiplexed SRM-ILIS analyses of plasma and CSF
      levels of codosed VHHs demonstrated that while all 4 VHHs have similar blood
      pharmacokinetics, only FC5 and FC44 show elevated CSF levels, suggesting that
      they are potential novel carriers for delivery of drugs and macromolecules across
      the BBB.

PMID- 23150992
TI  - Effect of early anti-retroviral therapy on the pathogenic changes in mucosal
      tissues of SIV infected rhesus macaques.
AB  - BACKGROUND: The gastrointestinal tissue plays an important role in the
      pathogenesis of HIV/SIV infection and serves as a viral reservoir in infected
      individuals under antiretroviral therapy (ART). However, the effect of ART
      administration in the very early stage of infection on HIV/SIV replication and
      pathogenesis in gastrointestinal tissue has not been fully studied. In this
      current study, rhesus monkeys infected with SIV were treated with ART starting at
      day 7 post-infection. The effect of early ART on SIV replication and infection
      related pathogenic changes in mucosal tissues of the infected monkeys was
      examined. METHODS: Nuclear acids were extracted from snap frozen ileum and colon
      tissues and mesentery lymph nodes from SIV infected monkeys with or without ART.
      SIV RNA and DNA loads as well as levels of CD3, CD4 and cytokine mRNA were
      measured by PCR and RT PCR from the isolated nuclear acids. Tissue sections were
      stained by immuno-fluorescence labeled antibodies for CD3 and CD4. RESULTS:
      Without ART treatment, these monkeys underwent a mild SIV infection with low
      viral loads and slightly decreased CD4+ T cell counts in peripheral blood. In ART
      treated monkeys, SIV RNA loads were undetectable in blood with normal CD4+ T cell
      counts, however, SIV RNA and DNA were detected in the intestinal tissues and
      mesentery lymph nodes although the levels were lower than those in untreated
      monkeys. The levels of CD3 and CD4 positive cells in the tissues were similar
      between the infected untreated monkeys and infected ART treated monkeys based on
      RT-PCR and immune-fluorescence staining of the tissue sections. Furthermore,
      compatible levels of IL-6, TNF-a, IL-1b and MyD88 mRNAs were detected in most of
      intestinal tissues and mesentery lymph nodes of infected ART treated and infected
      untreated monkeys. CONCLUSIONS: These results suggest that early ART
      administration could not effectively inhibit SIV replication in intestinal
      tissues and mesentery lymph nodes and could not reduce the immune activation
      induced by SIV infection in the intestinal tissues.

PMID- 23150994
TI  - Mechanistic insight into the formal [1,3]-migration in the thermal Claisen
      rearrangement.
AB  - The thermal formal [1,3]-sigmatropic shift of allyl aryl ethers has been studied
      in depth experimentally with the aid of the density functional theory (DFT)
      calculations of the B3LYP function. Three mechanistic possibilities, referred to
      as the radical, ionic, and concerted mechanisms, have previously been put forth
      to explain the thermal [1,3]-rearrangement process. However, the intercrossing
      and radical trapping experiments indicate the rearrangement is an intramolecular
      process. The computational studies reveal that the concerted C[1,3]-sigmatropic
      shift suffered from a higher energetic barrier to allow the rearrangement to
      proceed under the conditions used. However, a tandem O[1,3]-sigmatropic shift
      with a configuration inversion of the oxygen atom and [3,3]-sigmatropic shift
      (the Claisen rearrangement) is the most likely pathway for the formal [1,3]
      rearrangement. Furthermore, the rearrangement experiments with a designed
      optically active substrate and O[1,3]-sigmatropic shift examples verify the new
      cascade rearrangement. In addition, computational and experimental studies
      indicate that water molecule assists the proton shift during the isomerization.
      The combined methods provide the new insight into the mechanism of the thermal
      formal [1,3]-migration in the Claisen rearrangement and the novel O[1,3]
      sigmatropic shift as well.

PMID- 23150995
TI  - Noninvasive type 2 diabetes screening: clinical evaluation of SCOUT DS in an
      Asian Indian cohort.
AB  - OBJECTIVE: This study evaluated the noninvasive, point-of-care diabetes screening
      device, Scout DS (VeraLight Inc., Albuquerque, NM) (SCOUT), in a native Asian
      Indian cohort. RESEARCH DESIGN AND METHODS: SCOUT is a tabletop, skin
      fluorescence spectrometer that reports a risk score following a 3-4-min
      noninvasive measurement of a subject's left volar forearm. SCOUT, fasting plasma
      glucose (FPG), and hemoglobin A(1c) (A1C) were compared for detection of abnormal
      glucose tolerance (AGT) in a cohort of 256 subjects without previous diagnosis of
      diabetes or impaired glucose tolerance in Chennai, India. After an overnight
      fast, a 75-g, 2-h oral glucose tolerance test was administered, and AGT was
      defined as a plasma glucose value >= 140 mg/dL (7.8 mmol/dL). Sensitivity, false
      positive rate (FPR), and receiver-operating characteristics area under the curve
      for AGT detection were computed for SCOUT, FPG, and A1C. Intra-day
      reproducibility of SCOUT was assessed. RESULTS: SCOUT, FPG, and A1C (at
      respective thresholds of 50, 110 mg/dL, and 5.7%) exhibited sensitivities of 87%,
      32%, and 86%, respectively, and FPR of 52%, 3%, and 58%, respectively. For the
      177 subjects receiving a valid SCOUT Diabetes Score on both measurement attempts,
      the coefficient of variation was 5.8%, and the Pearson correlation was 0.91. A
      SCOUT score could be obtained on 91% of subjects after two attempts. CONCLUSIONS:
      The performance of SCOUT is similar to that of A1C, whereas FPG had a much lower
      sensitivity. SCOUT is an effective tool for AGT screening in Asian Indians.

PMID- 23150996
TI  - High-resolution epifluorescence and time-of-flight secondary ion mass
      spectrometry chemical imaging comparisons of single DNA microarray spots.
AB  - DNA microarray assay performance is commonly compromised by spot-spot probe and
      signal variations as well as heterogeneity within printed microspots. Accurate
      metrics for captured DNA target signal rely upon uniform spot distribution of
      both probe and target DNA to yield reliable hybridized signal. While often
      presumed, this is neither easily achieved nor often proven experimentally. High
      resolution imaging techniques were used to determine spot heterogeneity in
      identical DNA array microspots comprising varied ratios of unlabeled and dye
      labeled DNA probes contact-printed onto commercial arraying surfaces.
      Epifluorescence imaging data for individual array microspots were correlated with
      time-of-flight secondary ion mass spectrometry (TOF-SIMS) chemical state imaging
      of the same spots. Epifluorescence imaging intensity distinguished varying DNA
      density distributed both within a given spot and from spot to spot. TOF-SIMS
      chemical analysis confirmed these heterogeneous printed DNA distributions by
      tracking bound Cy3 dye, DNA base, and phosphate specific ion fragments often
      correlating to fluorescence patterns within identical spots. TOF-SIMS ion
      fragments originating from probe DNA and Cy3 dye are enriched in microspot
      centers, correlating with high fluorescence intensity regions. Both TOF-SIMS and
      epifluorescence support Marangoni flow effects on spot drying, with high-density
      DNA-Cy3 located in spot centers and nonhomogeneous DNA distribution within
      printed spots. Microspot image dimensional analysis results for DNA droplet
      spreading show differing DNA densities across printed spots. The study directly
      supports different DNA probe chemical and spatial microenvironments within spots
      that yield spot-spot signal variations known to affect DNA target hybridization
      efficiencies and kinetics. These variations critically affect probe-target duplex
      formation and DNA array signal generation.

PMID- 23150998
TI  - Editorial: regulation of GPCRs by the membrane environment.

PMID- 23150997
TI  - Response assessment in Waldenstrom macroglobulinaemia: update from the VIth
      International Workshop.
AB  - This report represents a further update of the consensus panel criteria for the
      assessment of clinical response in patients with Waldenstrom macroglobulinaemia
      (WM). These criteria have been updated in light of further data demonstrating an
      improvement in categorical responses with new drug regimens as well as
      acknowledgement of the fact that such responses are predictive of overall
      outcome. A number of key changes are proposed but challenges do however remain
      and these include the variability in kinetics of immunoglobulin M (IgM) reduction
      with different treatment modalities and the apparent discrepancy between IgM and
      bone marrow/tissue response noted with some regimens. Planned sequential bone
      marrow assessments are encouraged in clinical trials.

PMID- 23150999
TI  - Membrane domains and the "lipid raft" concept.
AB  - The bulk structure of biological membranes consists of a bilayer of amphipathic
      lipids. According to the fluid mosaic model proposed by Singer and Nicholson, the
      glycerophospholipid bilayer is a two-dimensional fluid construct that allows the
      lateral movement of membrane components. Different types of lateral interactions
      among membrane components can take place, giving rise to multiple levels of
      lateral order that lead to highly organized structures. Early observations
      suggested that some of the lipid components of biological membranes may play
      active roles in the creation of these levels of order. In the late 1980s, a
      diverse series of experimental findings collectively gave rise to the lipid raft
      hypothesis. Lipid rafts were originally defined as membrane domains, i.e.,
      ordered structures created as a consequence of the lateral segregation of
      sphingolipids and differing from the surrounding membrane in their molecular
      composition and properties. This definition was subsequently modified to
      introduce the notion that lipid rafts correspond to membrane areas stabilized by
      the presence of cholesterol within a liquid-ordered phase. During the past two
      decades, the concept of lipid rafts has become extremely popular among cell
      biologists, and these structures have been suggested to be involved in a great
      variety of cellular functions and biological events. During the same period,
      however, some groups presented experimental evidence that appeared to contradict
      the basic tenets that underlie the lipid raft concept. The concept is currently
      being re-defined, with greater consistency regarding the true nature and role of
      lipid rafts. In this article we will review the concepts, criticisms, and the
      novel confirmatory findings relating to the lipid raft hypothesis.

PMID- 23151000
TI  - Molecular modeling and simulation of membrane lipid-mediated effects on GPCRs.
AB  - Functioning of G protein-coupled receptors (GPCRs) is tightly linked to the
      membrane environment, but a molecular level understanding of the modulation of
      GPCR by membrane lipids is not available. However, specific receptor-lipid
      interactions as well as unspecific effects mediated by the bulk properties of the
      membrane (thickness, curvature, etc.) have been proposed to be key regulators of
      GPCR modulation. In this review, we examine computational efforts made towards
      modeling and simulation of (i) the complex behavior of membrane lipids, (ii)
      membrane lipid-GPCR interactions as well as membrane lipid-mediated effects on
      GPCRs and (iii) GPCR oligomerization in a native-like membrane environment. We
      propose that, from the perspective of computational modeling, all three of these
      components need to be addressed in order to achieve a deeper understanding of
      GPCR functioning. Presently, we are able to simulate numerous lipid properties
      applying advanced computational techniques, although some barriers, such as the
      time-length of these simulations, need to be overcome. Implementing three
      dimensional structures of GPCRs in such validated membrane systems can give novel
      insights in membrane-dependent receptor modulation and formation of higher order
      receptor complexes. Finally, more realistic GPCR-membrane models would provide a
      very useful tool in studying receptor behavior and its modulation by small drug
      like ligands, a relevant issue for drug discovery.

PMID- 23151001
TI  - Regulation of G protein-coupled receptor kinases by phospholipids.
AB  - G protein coupled-receptor (GPCR) kinases (GRKs) initiate the deactivation of
      GPCRs by phosphorylating their cytoplasmic loops and C-terminal tails. They are
      regulated not only by allosteric interactions with activated GPCRs, but also by
      the membrane environment itself. Herein we describe how the various GRKs are
      recruited to lipid bilayers and, where evident, how specific anionic
      phospholipids help regulate their activity. Using crystal structures representing
      each of the three vertebrate GRK subfamilies, we map the lipid binding sites in
      order to better understand how these enzymes are oriented at the cell surface.
      This analysis suggests that GRKs bind lipid and active GPCRs in a coordinated
      manner.

PMID- 23151002
TI  - Membrane lipids in the function of serotonin and adrenergic receptors.
AB  - G-protein coupled receptors (GPCRs) are the largest class of molecules involved
      in signal transduction across membranes, and represent major targets in the
      development of novel drug candidates in all clinical areas. Since GPCRs are
      integral membrane proteins, interaction of membrane lipids such as cholesterol
      and sphingolipids with GPCRs constitutes an emerging area of research in
      contemporary biology. Cholesterol and sphingolipids represent important lipid
      components of eukaryotic membranes and play a crucial role in a variety of
      cellular functions. In this review, we highlight the role of these vital lipids
      in the function of two representative GPCRs, the serotonin(1A) receptor and the
      adrenergic receptor. We believe that development in deciphering molecular details
      of the nature of GPCR-lipid interaction would lead to better insight into our
      overall understanding of GPCR function in health and disease.

PMID- 23151003
TI  - Metabotropic purinergic receptors in lipid membrane microdomains.
AB  - There is broad evidence that association of transmembrane receptors and
      signalling molecules with lipid rafts/caveolae provides an enriched environment
      for protein-protein interactions necessary for signal transduction, and a
      mechanism for the modulation of neurotransmitter and/or growth factor receptor
      function. Several receptors translocate into submembrane compartments after
      ligand binding, while others move in the opposite direction. The role of such a
      dynamic localization and functional facilitation is signalling modulation and
      receptor desensitization or internalization. Purine and pyrimidine nucleotides
      have been viewed as primordial precursors in the evolution of all forms of
      intercellular communication, and they are now regarded as fundamental
      extracellular signalling molecules. They propagate the purinergic signalling by
      binding to ionotropic and metabotropic receptors expressed on the plasma membrane
      of almost all cell types, tissues and organs. Here, we have illustrated the
      localization in lipid rafts/caveolae of G protein-coupled P1 receptors for
      adenosine and P2Y receptors for nucleoside tri- and di-phosphates. We have
      highlighted that microdomain partitioning of these purinergic GPCRs is cell
      specific, as is the overall expression levels of these same receptors. Moreover,
      we have described that disruption of submembrane compartments can shift the
      purinergic receptors from raft/caveolar to non-raft/non-caveolar fractions, and
      then abolish their ability to activate lipid signalling pathways and to integrate
      with additional lipid-controlled signalling events. This modulates the biological
      response to purinergic ligands and most of all indicates that the topology of the
      various purinergic components at the cell surface not only organizes the signal
      transduction machinery, but also controls the final cellular response.

PMID- 23151004
TI  - GPR55 and its interaction with membrane lipids: comparison with other
      endocannabinoid-binding receptors.
AB  - A number of integral membrane G protein-coupled receptors (GPCRs) share common
      structural features (including palmytoilated aminoacid residues and consensus
      sequences specific for interaction with cholesterol) that allow them to interact
      with lipid rafts, membrane cholesterol-rich microdomains able to regulate GPCR
      signalling and functions. Among GPCRs, type-1 and type-2 cannabinoid receptors,
      the molecular targets of endocannabinoids (eCBs), control many physiological and
      pathological processes through the activation of several signal transduction
      pathways. Recently, the orphan GPR55 receptor has been proved to be activated by
      many eCBs, thus leading to the hypothesis that it might be the "type-3"
      cannabinoid receptor. While the biological activity of eCBs and the influence of
      membrane lipids on their functions are rather well established, information
      regarding GPR55 is still scarce and often controversial. Based on this
      background, here we shall review current data about GPR55 pharmacology and
      signalling, highlighting its involvement in several pathophysiological
      conditions. We shall also outline the structural features that allow GPR55 to
      interact with cholesterol and to associate with lipid rafts; how the latter lipid
      microdomains impact the biological activity of GPR55 is also addressed, as well
      as their potential for the discovery of new therapeutics useful for the treatment
      of those human diseases that might be associated with alterations of GPR55
      activity.

PMID- 23151005
TI  - Cycloartane-3,24,25-triol inhibits MRCKalpha kinase and demonstrates promising
      anti prostate cancer activity in vitro.
AB  - BACKGROUND: Given the high occurrence of prostate cancer worldwide and one of
      the major sources of the discovery of new lead molecules being medicinal plants,
      this research undertook to investigate the possible anti-cancer activity of two
      natural cycloartanes; cycloartane-3,24,25-diol (extracted in our lab from
      Tillandsia recurvata) and cycloartane-3,24,25-triol (purchased). The inhibition
      of MRCKalpha kinase has emerged as a potential solution to restoring the tight
      regulation of normal cellular growth, the loss of which leads to cancer cell
      formation. METHODS: Kinase inhibition was investigated using competition binding
      (to the ATP sites) assays which have been previously established and
      authenticated and cell proliferation was measured using the WST-1 assay. RESULTS:
      Cycloartane-3,24,25-triol demonstrated strong selectivity towards the MRCKalpha
      kinase with a Kd50 of 0.26 MUM from a total of 451 kinases investigated.
      Cycloartane-3,24,25-triol reduced the viability of PC-3 and DU145 cell lines with
      IC50 values of 2.226 +/- 0.28 MUM and 1.67 +/- 0.18 MUM respectively.
      CONCLUSIONS: These results will prove useful in drug discovery as Cycloartane
      3,24,25-triol has shown potential for development as an anti-cancer agent against
      prostate cancer.

PMID- 23151006
TI  - Experts' opinions on terminology for complementary and integrative medicine - a
      qualitative study with leading experts.
AB  - BACKGROUND: Integrative medicine (IM) is currently the most commonly used term to
      describe the integration of complementary and alternative medicine (CAM) into
      conventional medicine. In the definitions of IM the most important feature is the
      focus on evidence as crucial factor for therapeutic decision-making. However,
      there are discussions on the term "integrative medicine" with the most notable
      critique from within CAM that it describes the integration of complementary
      methods into conventional institutions and into a "conventional framework of
      thinking". The aim of this qualitative study was to understand the thoughts of
      leading experts on IM and on the scientific debate in the field as well as their
      personal opinions about terminology in general. METHODS: We have conducted semi
      standardized interviews with ten leading experts in the field of CAM and
      integrative medicine in the USA, England, and Germany, who have had leading
      positions at medical schools or the NIH in 2010 and 2011. Interviews were
      recorded, transcribed and analyzed using content analysis with the qualitative
      analysis software maxqda. RESULTS: Overall the current terminology was seen as a
      problem, although most experts agreed that the term "integrative medicine" (IM)
      described well what they do or they think is useful for medical care. The
      terminology debate was discussed from four perspectives: 1) from the perspective
      of medical practice, 2) from the perspective of research, 3) from the perspective
      of public relations, and 4) from the perspective of health care delivery. These
      perspectives may be used to evaluate the appropriateness of different terms in
      use in the field. When interviewees discussed the terminology question, they also
      discussed the type of health care system they envisioned. Such reflections led
      the interviewees to caution about too narrow a focus on the terminology question.
      The question of naming was one about influencing and changing medicine.
      CONCLUSION: The discussion of the experts demonstrated that the discussion about
      terminology is an important debate about the shaping of medicine. The experts
      discussed terminology in the light of "how health care systems" should look like
      in the future.

PMID- 23151008
TI  - Arterial stiffness is increased in Hodgkin lymphoma survivors treated with
      radiotherapy.
AB  - Radiotherapy has been associated with an increased risk for cardiovascular
      disease (CVD) in Hodgkin lymphoma survivors (HLS). Identifying subjects most
      likely to develop these complications is challenging. Arterial stiffness has been
      frequently used as an early marker of CVD, but has never previously been
      investigated in patients treated with radiotherapy. The carotid-femoral pulse
      wave velocity (PWV) and the distensibility coefficient (DC) of the common carotid
      artery were used as markers of arterial stiffness. Eighty-two HLS and 40 age- and
      gender-matched control subjects were studied. The aorta and the carotid arteries
      were situated within the radiation field in 50 and 39 patients. Mean PWV was not
      significantly different in HLS treated with radiotherapy on the mediastinum when
      compared to HLS treated without mediastinal radiotherapy and to controls. If HLS
      were 40 years or older at radiotherapy their PWV was significantly higher (8.54
      m/s) than patients irradiated at a younger age (7.14 m/s, p = 0.004) and controls
      (6.91 m/s, p < 0.001), after adjusting for current age and other CVD risk
      factors. Mean DC was lower, indicative of stiffer arteries, in HLS treated with
      radiotherapy on the common carotid artery (2.79) than in HLS without radiotherapy
      (3.35, p = 0.029) and versus controls (3.60, p = 0.001). DC was lowest in HLS
      treated at 35 years of age or later (2.05), compared to HLS irradiated at a
      younger age (2.98, p = 0.046). In HLS, radiotherapy is associated with increased
      arterial stiffness. The effect of radiotherapy seems most evident when
      radiotherapy is administered at ages above 35-40 years.

PMID- 23151007
TI  - ROCK inhibitor Y-27632 increases the cloning efficiency of limbal stem/progenitor
      cells by improving their adherence and ROS-scavenging capacity.
AB  - Rho-associated coiled-coil kinase (ROCK) inhibitor Y-27632 has been shown to
      increase proliferative capacity and even immortalize primary keratinocytes. Here,
      we demonstrate that rabbit primary limbal epithelial cells (LECs) treated with Y
      27632 also exhibited improved colony-forming efficiency by enhancing the
      expansion of the stem/progenitor cells. Moreover, Y-27632 treatment improved the
      rapid adherence of limbal stem/progenitor cells in the initial inoculation of
      primary cells. In addition, Y-27632 treatment elevated the intracellular
      glutathione level and decreased cellular reactive oxygen species (ROS)
      accumulation during the expansion of LECs. Therefore, ROCK inhibitor Y-27632
      increased the cloning efficiency of rabbit limbal stem/progenitor cells by
      improving their adherence and ROS scavenging capacity.

PMID- 23151009
TI  - Integrated working between residential care homes and primary care: a survey of
      care homes in England.
AB  - BACKGROUND: Older people living in care homes in England have complex health
      needs due to a range of medical conditions, mental health needs and frailty.
      Despite an increasing policy expectation that professionals should operate in an
      integrated way across organisational boundaries, there is a lack of understanding
      between care homes and the National Health Service (NHS) about how the two
      sectors should work together, meaning that residents can experience a poor "fit"
      between their needs, and services they can access. This paper describes a survey
      to establish the current extent of integrated working that exists between care
      homes and primary and community health and social services. METHODS: A self
      completion, online questionnaire was designed by the research team. Items on the
      different dimensions of integration (funding, administrative, organisational,
      service delivery, clinical care) were included. The survey was sent to a random
      sample of residential care homes with more than 25 beds (n = 621) in England in
      2009. Responses were analysed using quantitative and qualitative methods.
      RESULTS: The survey achieved an overall response rate of 15.8%. Most care homes
      (78.7%) worked with more than one general practice. Respondents indicated that a
      mean of 14.1 professionals/ services (other than GPs) had visited the care homes
      in the last six months (SD 5.11, median 14); a mean of .39 (SD.163)
      professionals/services per bed. The most frequent services visiting were district
      nursing, chiropody and community psychiatric nurses. Many (60%) managers
      considered that they worked with the NHS in an integrated way, including sharing
      documents, engaging in integrated care planning and joint learning and training.
      However, some care home managers cited working practices dictated by NHS methods
      of service delivery and priorities for care, rather than those of the care home
      or residents, a lack of willingness by NHS professionals to share information,
      and low levels of respect for the experience and knowledge of care home staff.
      CONCLUSIONS: Care homes are a hub for a wide range of NHS activity, but this is
      ad hoc with no recognised way to support working together. Integration between
      care homes and local health services is only really evident at the level of
      individual working relationships and reflects patterns of collaborative working
      rather than integration. More integrated working between care homes and primary
      health services has the potential to improve quality of care in a cost-effective
      manner, but strategic decisions to create more formal arrangements are required
      to bring this about. Commissioners of services for older people need to
      capitalise on good working relationships and address idiosyncratic patterns of
      provision to care homes.The low response rate is indicative of the difficulty of
      undertaking research in care homes.

PMID- 23151010
TI  - Expression of both matrix metalloproteinase-2 and its tissue inhibitor-2 in
      tunica media of radial artery in uremic patients.
AB  - OBJECTIVE: To investigate the expression and clinical significance of both matrix
      metalloproteinase-2 (MMP-2) and its tissue inhibitor (tissue inhibitor of
      metalloproteinase-2 (TIMP-2)) in tunica media of radial artery in uremic
      patients. METHODS: The modified radial arteries from 80 uremic patients during
      internal arteriovenous fistula surgery were selected and used as experimental
      specimens. The calcification of tunica media was observed by alizarin red
      staining, and the expression status of MMP-2, TIMP-2, osteoprotegerin (OPG), and
      osteopontin (OPN) in tunica media of radial arteries of these patients was
      detected by immunohistochemical method. The semiquantitative analysis and
      comparison were conducted based on the calcification grading and the expression
      of each test protein in tunica media of radial artery. RESULTS: Of the 80 cases
      of radial artery specimens, 37 cases were presented with various degrees of
      calcification of tunica media, and the calcification rate was 46.25%; the
      expression of MMP-2, TIMP-2, OPG, and OPN could be detected in the calcificated
      tunica media of the radial artery and was positively correlated with the degree
      of vascular calcification (p < 0.05). CONCLUSION: The incidence of vascular
      calcification in uremic patients was high. The occurrence of calcification in
      tunica media of the radial artery was correlated with the expression of MMP-2 and
      TIMP-2.

PMID- 23151011
TI  - Picosecond pulse radiolysis study on the distance dependent reaction of the
      solvated electron with organic molecules in ethylene glycol.
AB  - The decay of solvated electron e(s)(-) is observed by nanosecond and picosecond
      pulsed radiolysis, in diluted and highly concentrated solutions of
      dichloromethane, CH(2)Cl(2), trichloromethane, CHCl(3), tribromomethane, CHBr(3),
      acetone, CH(3)COCH(3), and nitromethane, CH(3)NO(2), prepared in ethylene glycol.
      First, second-order rate constants for the reactions between e(-)(s) and the
      organic scavengers have been determined. The ratio between the highest rate
      constant that was found for CH(3)NO(2) and the lowest one that was found for
      acetone is 3. This difference in reactivity cannot be explained by the change of
      viscosity or the size of the molecules. Then, from the analysis of decay kinetics
      obtained using ultrafast pulse-probe method, the distance dependent first-order
      rate constant of electron transfer for each scavenger has been determined. The
      amplitude of the transient effect observed on the picosecond time scale differs
      strongly between these solvated electron scavengers. For an identical scavenger
      concentration, the transient effect lasts ~650 ps for CH(3)NO(2) compared to ~200
      ps for acetone. For acetone, the distance dependent first-order rate constant of
      electron transfer is decreasing very rapidly with increasing distance, whereas
      for nitromethane and tribromomethane the rate constant is decreasing gradually
      with the distance and its value remains non-negligible even at ~10 A. This rate
      constant is controlled mostly by the free energy of the reaction. For
      nitromethane and tribromomethane, the driving force is great, and the reaction
      can occur even at long distance, whereas for acetone the driving force is small
      and the reaction occurs almost at the contact distance. For nitromethane and
      acetone, the one-electron reduction reaction needs less internal reorganization
      energy than for alkyl halide compounds for which the reaction occurs in concert
      with bond breaking and geometric adjustment.

PMID- 23151012
TI  - Prenatal diagnostic conundrum involving a novel ATP7A duplication.

PMID- 23151013
TI  - Carbamate derivatives of indolines as cholinesterase inhibitors and antioxidants
      for the treatment of Alzheimer's disease.
AB  - The cascade of events that occurs in Alzheimer's disease involving oxidative
      stress and the reduction in cholinergic transmission can be better addressed by
      multifunctional drugs than cholinesterase inhibitors alone. For this purpose, we
      prepared a large number of derivatives of indoline-3-propionic acids and esters.
      They showed scavenging activity against different radicals in solution and
      significant protection against cytotoxicity in cardiomyocytes and primary
      cultures of neuronal cells exposed to H2O2 species and serum deprivation at
      concentrations ranging from 1 nM to 10 MUM depending on the compound. For most of
      the indoline-3-propionic acid derivatives, introduction of N-methyl-N-ethyl or N
      methyl-N-(4-methoxyphenyl) carbamate moieties at positions 4, 6, or 7 conferred
      both acetyl (AChE) and butyryl (BuChE) cholinesterase inhibitory activities at
      similar concentrations to those that showed antioxidant activity. The most potent
      AChE inhibitors were 120 (3-(2-aminoethyl) indolin-4-yl ethyl(methyl)carbamate
      dihydrochloride) and 94 (3-(3-methoxy-3-oxopropyl)-4-(((4-methoxyphenyl)(methyl)
      carbamoyl)oxy)indolin-1-ium hydrochloride) with IC50s of 0.4 and 1.2 MUM,
      respectively.

PMID- 23151014
TI  - Luminescent rhenium and ruthenium complexes of an amphoteric poly(amidoamine)
      functionalized with 1,10-phenanthroline.
AB  - A new amphoteric copolymer, PhenISA, has been obtained by copolymerization of 4
      (4'-aminobutyl)-1,10-phenanthroline (BAP) with 2-methylpiperazine and
      bis(acrylamido)acetic acid (BAC) (6% of phenanthroline-containing repeating
      units). The copolymer showed excellent solubility in water, where it self
      aggregated to give clear nanoparticle suspensions (hydrodynamic diameter = 21 +/-
      2 nm, by dynamic light scattering (DLS) analysis). The phenanthroline pendants of
      the polymer stably coordinated either Re(CO)(3)(+) or Ru(phen)(2)(2+) fragments,
      affording luminescent Re-PhenISA, Re-Py-PhenISA, and Ru-PhenISA polymer
      complexes, emitting from triplet metal-to-ligand charge transfer ((3)MLCT)
      excited states (with lambda(em) = 608, 571, and 614 nm, respectively, and
      photoluminescence quantum yields Phi(em) = 0.7%, 4.8%, and 4.1%, in aerated water
      solution, respectively). DLS analyses indicated that the polymer complexes
      maintained the nanosize of PhenISA. All the complexes were stable under
      physiological conditions (pH 7.4, 0.15 M NaCl) in the presence of an excess of
      the ubiquitous competitor cysteine. In vitro viability assays showed no toxicity
      of Re-Py-PhenISA and Ru-PhenISA complexes, at concentrations in the range of 0.5
      50 MUM (calculated on the metal-containing unit), toward HEK-293 (human embryonic
      kidney) cells. A preliminary investigation of internalization in HEK-293 cells,
      by means of fluorescence confocal microscopy, showed that Ru-PhenISA enters cells
      via an endocytic pathway and, subsequently, homogeneously diffuse within the
      cytoplasm across the vesicle membranes.

PMID- 23151016
TI  - Self-supporting oxygen reduction electrocatalysts made from a nitrogen-rich
      network polymer.
AB  - We report the design, synthesis, and evaluation of a new type of non-precious
      metal catalyst made from network polymers. 2,6-Diaminopyridine was selected as a
      building-block monomer for the formation of a nitrogen-rich network polymer that
      forms self-supporting spherical backbone structures and contains a high density
      of metal-coordination sites. A Co-/Fe-coordinating pyrolyzed polymer exhibited a
      high specific oxygen reduction activity with onset and half-wave potentials of
      0.87 and 0.76 V vs RHE, respectively, in neutral media. There was no crossover
      effect of organics on its activity. The power output of a microbial fuel cell
      equipped with this catalyst on its cathode was more than double the output with a
      commercial 20 wt % Pt/C catalyst.

PMID- 23151015
TI  - Toll-like receptor 3 gene polymorphisms and severity of pandemic A/H1N1/2009
      influenza in otherwise healthy children.
AB  - BACKGROUND: Toll-like receptors (TLRs) form an essential part of the innate
      immune system, which plays a fundamental role in rapidly and effectively
      controlling infections and initiating adaptive immunity. There are no published
      data concerning the importance of polymorphisms of TLRs in conditioning
      susceptibility to influenza or the severity of the disease. The aim of this study
      was to evaluate whether selected polymorphisms of TLR2, TLR3 and TLR4 influence
      the incidence and clinical picture of pandemic A/H1N1/2009 influenza. RESULTS:
      The study involved 272 healthy children attending our Emergency Room for
      influenza-like illness (ILI), including 51 (18.8%) with pandemic A/H1N1/2009
      influenza as revealed by real-time polymerase chain reaction, and 164 healthy
      controls examined after minor surgery. Genomic DNA was extracted from whole blood
      samples and five single-nucleotide polymorphisms (SNPs) were studied: TLR2
      rs5743708, TLR3 rs5743313, TLR3 rs5743315, TLR4 rs4986790 and TLR4 rs4986791. The
      TLR3 rs5743313/CT polymorphism was found in all of the children with pneumonia
      and influenza infection, but in a significantly smaller number of those with
      A/H1N1/2009 influenza without pneumonia (<0.0001). TLR2, TLR3 rs5743315/AC and
      TLR4 polymorphisms were equally distributed in all of the groups regardless of
      the presence of the pandemic A/H1N1/2009 virus and clinical diagnosis. Viral load
      was comparable in all of the study groups. CONCLUSIONS: There is a close
      relationship between the presence of TLR3 rs5743313/CT and an increased risk of
      pneumonia in children infected by the pandemic A/H1N1/2009 influenza virus.

PMID- 23151017
TI  - Prevalence of glucose intolerance among children and adolescents in urban South
      India (ORANGE-2).
AB  - AIM: This study was designed to determine the prevalence of glucose intolerance
      (prediabetes or diabetes) in children and adolescents in urban South India.
      SUBJECTS AND METHODS: Children (6-11 years old) and adolescents (12-19 years old)
      (n=1,519; 777 boys and 742 girls) were randomly selected from residential
      apartments representing the 10 corporation zones of Chennai city. Height, weight,
      waist circumference, body fat percentage, and blood pressure were measured using
      standardized techniques. Investigations included oral glucose tolerance test
      (OGTT), lipid profile, and fasting insulin. Insulin resistance (IR) was assessed
      by homeostasis model assessment (HOMA-IR). RESULTS: The overall prevalence of
      glucose intolerance was 3.7% but was higher in girls compared with boys (4.2% vs.
      3.2%, P<0.001) and increased to 12.7% in girls with abdominal obesity. On
      univariate regression, the following risk factors showed significant association
      with glucose intolerance in girls: adolescent age group (odds ratio [OR] 2.94;
      confidence interval (CI) 1.12, 7.76), waist circumference (OR 4.45; CI 1.95,
      10.14), body mass index (OR 2.73; CI 1.32, 5.65), acanthosis nigricans (OR 2.35;
      CI 1.14, 4.83), family history of diabetes (OR 2.52; CI 1.07, 5.92), and HOMA-IR
      (OR 9.30; CI 3.59, 24.12). On multivariate analysis, only family history of
      diabetes (OR 4.11; CI 1.28, 13.22; P=0.018) and HOMA-IR (OR 11.22; CI 4.19,
      30.05; P<0.001) remained significant. In boys only HOMA-IR (OR 5.19; CI 1.54,
      17.44; P=0.008) was associated with glucose intolerance. CONCLUSIONS: The
      prevalence of glucose intolerance is high in Asian Indian adolescents,
      particularly in girls with abdominal obesity.

PMID- 23151018
TI  - Detection of ligand binding to proteins through observation of hydration water.
AB  - Drug development is impeded by the need to design for each drug target a test
      that detects the binding of drug candidate molecules to the target protein.
      Therefore, a general method to detect ligand binding is highly desirable. Here,
      we present an observation toward developing such a method, which is based on
      monitoring a change in water absorption by infrared spectroscopy. Infrared
      spectroscopy has high sensitivity for water, and changes in its hydrogen bond
      pattern can be observed. We studied absorption changes of water upon the addition
      of phosphenolpyruvate or Mg(2+) to pyruvate kinase. In each case, there is a
      decrease in the absorption of water in the 3000-3100 cm(-1) region on the low
      wavenumber side of the OH stretching vibration when a ligand binds to the
      protein. Our results suggest that the weaker water absorption is due to the
      release of protein-bound water into bulk water during ligand binding. This
      observation has high potential for drug development as well as for basic research
      because it can lead to a general method for detecting molecular association
      events that (i) is label-free, (ii) works with both binding partners being in
      aqueous solution, and (iii) is based on a universal process that takes place in
      all binding events.

PMID- 23151020
TI  - Molecular design of organic superbases, azacalix[3](2,6)pyridines: catalysts for
      1,2- and 1,4-additions.
AB  - The molecular design, characteristics, and catalytic activity of macrocyclic
      amino compounds, azacalix[3](2,6)pyridine derivatives, were studied. The
      introduction of an electron-donating group on the pyridine moiety and bridging
      amino phenyl group enabled the enhancement of the basicity of
      azacalix[3](2,6)pyridine up to pK(BH(+)) = 29.5 in CD(3)CN. These derivatives
      were shown to be efficient catalysts for 1,4-addition reactions of nitroalkanes
      or primary alcohols to alpha,beta-unsaturated carbonyl compounds and 1,2-addition
      reactions of nitroalkanes to aromatic aldehydes.

PMID- 23151019
TI  - An efficient and practical radiosynthesis of [11C]temozolomide.
AB  - Temozolomide (TMZ) is a prodrug for an alkylating agent used for the treatment of
      malignant brain tumors. A positron emitting version, [(11)C]TMZ, has been
      utilized to help elucidate the mechanism and biodistribution of TMZ. Challenges
      in [(11)C]TMZ synthesis and reformulation make it difficult for routine
      production. A highly reproducible one-pot radiosynthesis of [(11)C]TMZ with a
      radiochemical yield of 17 +/- 5% and >=97% radiochemical purity is reported.

PMID- 23151021
TI  - Molecular characterisation of cell line models for triple-negative breast
      cancers.
AB  - BACKGROUND: Triple-negative breast cancers (BC) represent a heterogeneous subtype
      of BCs, generally associated with an aggressive clinical course and where
      targeted therapies are currently limited. Target validation studies for all BC
      subtypes have largely employed established BC cell lines, which have proven to be
      effective tools for drug discovery. RESULTS: Given the lines of evidence
      suggesting that BC cell lines are effective tools for drug discovery, we assessed
      the similarities between triple-negative BCs and cell lines, to identify in vitro
      representatives, modelling the diversity within this BC subtype. 25 BC cell
      lines, enriched for those lacking ER, PR and HER2 expression, were subjected to
      transcriptomic, genomic and epigenomic profiling analyses and comparisons were
      made to existing knowledge of corresponding perturbations in triple-negative BCs.
      Transcriptional analysis segregated ER-negative BC cell lines into three groups,
      displaying distinctive abundances for genes involved in epithelial-mesenchymal
      transition, apocrine and high-grade carcinomas. DNA copy number aberrations of
      triple-negative BCs were well represented in cell lines and genes with
      coordinately altered gene expression showed similar patterns in tumours and cell
      lines. Methylation events in triple-negative BCs were mostly retained in
      epigenomes of cell lines. Combined methylation and gene expression analyses
      revealed a subset of genes characteristic of the Claudin-low BC subtype,
      exhibiting epigenetic-regulated gene expression in BC cell lines and tumours,
      suggesting that methylation patterns are likely to underpin subtype-specificity.
      CONCLUSION: Here, we provide a comprehensive analysis of triple-negative BC
      features on several molecular levels in BC cell lines, thereby creating an in
      depth resource to access the suitability of individual lines as experimental
      models for studying BC tumour biology, biomarkers and possible therapeutic
      targets in the context of preclinical target validation.

PMID- 23151022
TI  - In vitro and in vivo anti-tumor effect of metformin as a novel therapeutic agent
      in human oral squamous cell carcinoma.
AB  - BACKGROUND: Metformin, which is widely used as an antidiabetic agent, has
      recently been reported to reduce cancer risk and improve prognosis in certain
      malignancies. However, the specific mechanisms underlying the effect of metformin
      on the development and progression of several cancers including oral squamous
      cell carcinoma (OSCC) remain unclear. In the present study, we investigated the
      effects of metformin on OSCC cells in vitro and in vivo. METHODS: OSCC cells
      treated with or without metformin were counted using a hemocytometer. The
      clonogenic ability of OSCC cells after metformin treatment was determined by
      colony formation assay. Cell cycle progression and apoptosis were assessed by
      flow cytometry, and the activation of related signaling pathways was examined by
      immunoblotting. The in vivo anti-tumor effect of metformin was examined using a
      xenograft mouse model. Immunohistochemistry and TUNEL staining were used to
      determine the expression of cyclin D1 and the presence of apoptotic cells in
      tumors from mice treated with or without metformin. RESULTS: Metformin inhibited
      proliferation in the OSCC cell lines CAL27, WSU-HN6 and SCC25 in a time- and dose
      dependent manner, and significantly reduced the colony formation of OSCC cells in
      vitro. Metformin induced an apparent cell cycle arrest at the G0/G1 phase, which
      was accompanied by an obvious activation of the AMP kinase pathway and a strongly
      decreased activation of mammalian target of rapamycin and S6 kinase. Metformin
      treatment led to a remarkable decrease of cyclin D1, cyclin-dependent kinase
      (CDK) 4 and CDK6 protein levels and phosphorylation of retinoblastoma protein,
      but did not affect p21 or p27 protein expression in OSCC cells. In addition,
      metformin induced apoptosis in OSCC cells, significantly down-regulating the anti
      apoptotic proteins Bcl-2 and Bcl-xL and up-regulating the pro-apoptotic protein
      Bax. Metformin also markedly reduced the expression of cyclin D1 and increased
      the numbers of apoptotic cells in vivo, thus inhibiting the growth of OSCC
      xenografts. CONCLUSIONS: Our data suggested that metformin could be a potential
      candidate for the development of new treatment strategies for human OSCC.

PMID- 23151024
TI  - Visualizing and quantifying dose distribution in a UV reactor using three
      dimensional laser-induced fluorescence.
AB  - Evaluating the performance of typical water treatment UV reactors is challenging
      due to the complexity in assessing spatial and temporal variation of UV fluence,
      resulting from highly unsteady, turbulent nature of flow and variation in UV
      intensity. In this study, three-dimensional laser-induced fluorescence (3DLIF)
      was applied to visualize and quantitatively analyze a lab-scale UV reactor
      consisting of one lamp sleeve placed perpendicular to flow. Mapping the spatial
      and temporal fluence delivery and MS2 inactivation revealed the highest local
      fluence in the wake zone due to longer residence time and higher UV exposure,
      while the lowest local fluence occurred in a region near the walls due to short
      circuiting flow and lower UV fluence rate. Comparing the tracer based
      decomposition between hydrodynamics and IT revealed similar coherent structures
      showing the dependency of fluence delivery on the reactor flow. The location of
      tracer injection, varying the height and upstream distance from the lamp center,
      was found to significantly affect the UV fluence received by the tracer. A
      Lagrangian-based analysis was also employed to predict the fluence along specific
      paths of travel, which agreed with the experiments. The 3DLIF technique developed
      in this study provides new insight on dose delivery that fluctuates both
      spatially and temporally and is expected to aid design and optimization of UV
      reactors as well as validate computational fluid dynamics models that are widely
      used to simulate UV reactor performances.

PMID- 23151023
TI  - Electric nets and sticky materials for analysing oviposition behaviour of gravid
      malaria vectors.
AB  - BACKGROUND: Little is known about how malaria mosquitoes locate oviposition sites
      in nature. Such knowledge is important to help devise monitoring and control
      measures that could be used to target gravid females. This study set out to
      develop a suite of tools that can be used to study the attraction of gravid
      Anopheles gambiae s.s. towards visual or olfactory cues associated with aquatic
      habitats. METHODS: Firstly, the study developed and assessed methods for using
      electrocuting nets to analyse the orientation of gravid females towards an
      aquatic habitat. Electric nets (1m high * 0.5m wide) were powered by a 12V
      battery via a spark box. High and low energy settings were compared for mosquito
      electrocution and a collection device developed to retain electrocuted mosquitoes
      when falling to the ground. Secondly, a range of sticky materials and a detergent
      were tested to quantify if and where gravid females land to lay their eggs, by
      treating the edge of the ponds and the water surface. A randomized complete block
      design was used for all experiments with 200 mosquitoes released each day.
      Experiments were conducted in screened semi-field systems using insectary-reared
      An. gambiae s.s. Data were analysed by generalized estimating equations. RESULTS:
      An electric net operated at the highest spark box energy of a 400 volt direct
      current made the net spark, creating a crackling sound, a burst of light and a
      burning smell. This setting caught 64% less mosquitoes than a net powered by
      reduced voltage output that could neither be heard nor seen (odds ratio (OR)
      0.46; 95% confidence interval (CI) 0.40-0.53, p < 0.001). Three sticky boards
      (transparent film, glue coated black fly-screen and yellow film) were evaluated
      as catching devices under electric nets and the transparent and shiny black
      surfaces were found highly attractive (OR 41.6, 95% CI 19.8 - 87.3, p < 0.001 and
      OR 28.8, 95% CI 14.5 - 56.8, p < 0.001, respectively) for gravid mosquitoes to
      land on compared to a yellow sticky film board and therefore unsuitable as
      collection device under the e-nets. With a square of four e-nets around a pond
      combined with yellow sticky boards on average 33% (95% CI 28-38%) of mosquitoes
      released were collected. Sticky materials and detergent in the water worked well
      in collecting mosquitoes when landing on the edge of the pond or on the water
      surface. Over 80% of collected females were found on the water surface (mean 103,
      95% CI 93-115) as compared to the edge of the artificial pond (mean 24, 95% CI 20
      28). CONCLUSION: A square of four e-nets with yellow sticky boards as a
      collection device can be used for quantifying the numbers of mosquitoes
      approaching a small oviposition site. Shiny sticky surfaces attract gravid
      females possibly because they are visually mistaken as aquatic habitats. These
      materials might be developed further as gravid traps. Anopheles gambiae s.s.
      primarily land on the water surface for oviposition. This behaviour can be
      exploited for the development of new trapping and control strategies.

PMID- 23151025
TI  - Identification of SLC26A4 c.919-2A>G compound heterozygosity in hearing-impaired
      patients to improve genetic counseling.
AB  - BACKGROUND: Mutations in the SLC26A4 gene, which encodes the anion transporter,
      pendrin, are a major cause of autosomal recessive non-syndromic hearing loss
      (NSHL) in some Asian populations. SLC26A4 c.919-2A>G (IVS7-2A>G) is the most
      common mutation in East Asian deaf populations. To provide a basis for improving
      the clinical diagnosis of deaf patients, we evaluated 80 patients with the
      SLC26A4 c.919-2A>G monoallelic mutation from 1065 hearing-impaired subjects and
      reported the occurrence of a second mutant allele in these patients. METHODS: The
      occurrence of a second mutant allele in these 80 patients with a single c.919
      2A>G mutation was investigated. Mutation screening was performed by bidirectional
      sequencing in SLC26A4 exons 2 to 6 and 9 to 21. RESULTS: We found that 47/80
      patients carried another SLC26A4 c.919-2A>G compound mutation. The five most
      common mutations were: p.H723R, p.T410M, 15+5G>A (c.1705+5G>A), p.L676Q and
      p.N392Y. We found a Chinese-specific SLC26A4 mutation spectrum and an associated
      SLC26A4 contribution to deafness. CONCLUSION: Our study illustrates that mutation
      analysis of other SLC26A4 exons should be undertaken in deaf patients with a
      single heterozygous SLC26A4 mutation. Moreover, a model of compound
      heterozygosity may partially explain the disease phenotype.

PMID- 23151026
TI  - Crystal structures and kinetics of monofunctional proline dehydrogenase provide
      insight into substrate recognition and conformational changes associated with
      flavin reduction and product release.
AB  - Proline dehydrogenase (PRODH) catalyzes the FAD-dependent oxidation of proline to
      Delta(1)-pyrroline-5-carboxylate, which is the first step of proline catabolism.
      Here, we report the structures of proline dehydrogenase from Deinococcus
      radiodurans in the oxidized state complexed with the proline analogue L
      tetrahydrofuroic acid and in the reduced state with the proline site vacant. The
      analogue binds against the si face of the FAD isoalloxazine and is protected from
      bulk solvent by helix alpha8 and the beta1-alpha1 loop. The FAD ribityl chain
      adopts two conformations in the E-S complex, which is unprecedented for
      flavoenzymes. One of the conformations is novel for the PRODH superfamily and may
      contribute to the low substrate affinity of Deinococcus PRODH. Reduction of the
      crystalline enzyme-inhibitor complex causes profound structural changes,
      including 20 degrees  butterfly bending of the isoalloxazine, crankshaft rotation
      of the ribityl, shifting of alpha8 by 1.7 A, reconfiguration of the beta1-alpha1
      loop, and rupture of the Arg291-Glu64 ion pair. These changes dramatically open
      the active site to facilitate product release and allow electron acceptors access
      to the reduced flavin. The structures suggest that the ion pair, which is
      conserved in the PRODH superfamily, functions as the active site gate.
      Mutagenesis of Glu64 to Ala decreases the catalytic efficiency 27-fold, which
      demonstrates the importance of the gate. Mutation of Gly63 decreases the
      efficiency 140-fold, which suggests that flexibility of the beta1-alpha1 loop is
      essential for optimal catalysis. The large conformational changes that are
      required to form the E-S complex suggest that conformational selection plays a
      role in substrate recognition.

PMID- 23151027
TI  - Subset optimization by reference matching (STORM): an optimized statistical
      approach for recovery of metabolic biomarker structural information from 1H NMR
      spectra of biofluids.
AB  - We describe a new multivariate statistical approach to recover metabolite
      structure information from multiple (1)H NMR spectra in population sample sets.
      Subset optimization by reference matching (STORM) was developed to select subsets
      of (1)H NMR spectra that contain specific spectroscopic signatures of biomarkers
      differentiating between different human populations. STORM aims to improve the
      visualization of structural correlations in spectroscopic data by using these
      reduced spectral subsets containing smaller numbers of samples than the number of
      variables (n ? p). We have used statistical shrinkage to limit the number of
      false positive associations and to simplify the overall interpretation of the
      autocorrelation matrix. The STORM approach has been applied to findings from an
      ongoing human metabolome-wide association study on body mass index to identify a
      biomarker metabolite present in a subset of the population. Moreover, we have
      shown how STORM improves the visualization of more abundant NMR peaks compared to
      a previously published method (statistical total correlation spectroscopy,
      STOCSY). STORM is a useful new tool for biomarker discovery in the "omic"
      sciences that has widespread applicability. It can be applied to any type of
      data, provided that there is interpretable correlation among variables, and can
      also be applied to data with more than one dimension (e.g., 2D NMR spectra).

PMID- 23151028
TI  - Collective magnetism at multiferroic vortex domain walls.
AB  - Cross-coupled phenomena of multiferroic domains and domain walls are of
      fundamental scientific and technological interest. Using cryogenic magnetic force
      microscopy, we find alternating net magnetic moments at ferroelectric domain
      walls around vortex cores in multiferroic hexagonal ErMnO(3), which correlate
      with each other throughout the entire vortex network. This collective nature of
      domain wall magnetism originates from the uncompensated Er(3+) moments at domain
      walls and the self-organization of the vortex network. Our results demonstrate
      that the collective domain wall magnetism can be controlled by external magnetic
      fields and represent a major advancement in the manipulation of local magnetic
      moments by harnessing cross-coupled domain walls.

PMID- 23151029
TI  - Effects of Launaea procumbens on brain antioxidant enzymes and cognitive
      performance of rat.
AB  - BACKGROUND: Launaea procumbens is used in the treatment of oxidative stress and
      mental disorders. The effects of Launaea procumbens methanolic extracts (LPMEs),
      i.e., 100 and 200 LPME mg/kg body weight (b.w.), on cognitive performance as well
      as on the activity of acetylcholinesterase, and antioxidant enzymes in rat brain
      tissue homogenates were evaluated. METHODS: Thirty male Sprague-Dawley rats were
      divided equally into three groups. Rats in group I (control) were given saline
      (vehicle), group II received LPME (100 mg/kg b.w., p.o.), and group III were
      treated with LPME (200 mg/kg b.w., p.o.) in dimethyl sulfoxide (DMSO) for 7 days.
      Antioxidant potential was assessed by measuring the activity of the antioxidant
      enzymes superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase
      (GSHpx), glutathione reductase (GSR) and glutathione-S-transferase (GST) as well
      as lipid peroxidation and glutathione (GSH) contents in brain tissue homogenates.
      Activity of acetylcholinesterase (AChE) and cognitive performance were also
      assessed. RESULTS: LPME administration reduced the levels of lipid peroxidation
      products (TBARS contents), increased GSH levels and enhanced the activities of
      SOD, CAT, GSHpx, GSR and GST. AChE activity was reduced by LPME treatment
      compared with untreated controls. CONCLUSION: These findings suggested the
      significant impact of LPMEs on brain function. These effects could be through the
      antioxidant effects of the bioactive constituents present in LPME.

PMID- 23151030
TI  - Autoantibodies to erythropoietin receptor in patients with immune-mediated
      diseases: relationship to anaemia with erythroid hypoplasia.
AB  - The prevalence, clinical associations and pathogenic role of newly identified
      autoantibodies to the erythropoietin receptor (EPOR) in patients with anaemia
      were investigated. Sera from 203 patients with immune-related or chronic kidney
      diseases were screened for anti-EPOR antibodies by enzyme-linked immunosorbent
      assay, and antibody specificity was evaluated by immunoprecipitating EPOR from AS
      E2 cells using purified immunoglobulin (Ig) fractions. In addition, the
      pathogenic role of anti-EPOR antibodies was determined by examining their
      inhibitory effects on AS-E2 cell proliferation. Clinical findings were compared
      between patients with and without anti-EPOR antibodies, in all patients and those
      with systemic lupus erythematosus (SLE). Serum anti-EPOR antibodies were detected
      in 52 patients. Purified IgG or IgM fractions from anti-EPOR antibody-positive
      sera immunoprecipitated EPOR and inhibited the EPO-dependent proliferation of AS
      E2 cells in a dose-dependent manner. Anti-EPOR antibodies were associated with
      low haemoglobin concentrations and reticulocytopenia in all patients enrolled and
      those with SLE. Further, there was a negative correlation between the levels of
      anti-EPOR antibodies and the number of bone marrow erythroblasts in patients who
      underwent bone marrow examinations. These findings suggest that EPOR
      autoantibodies are present in a subset of patients with anaemia and that impaired
      erythropoiesis can be mediated by anti-EPOR antibodies, which functionally
      neutralize EPO activity.

PMID- 23151032
TI  - Biofuel combustion. Energetics and kinetics of hydrogen abstraction from carbon-1
      in n-butanol by the hydroperoxyl radical calculated by coupled cluster and
      density functional theories and multistructural variational transition-state
      theory with multidimensional tunneling.
AB  - Multistructural canonical variational transition-state theory with small
      curvature multidimensional tunneling (MS-CVT/SCT) is employed to calculate
      thermal rate constants for hydrogen-atom abstraction from carbon-1 of n-butanol
      by the hydroperoxyl radical over the temperature range 250-2000 K. The M08-SO
      hybrid meta-GGA density functional was validated against CCSD(T)-F12a explicitly
      correlated wave function calculations with the jul-cc-pVTZ basis set. It was then
      used to compute the properties of all stationary points and the energies and
      Hessians of a few nonstationary points along the reaction path, which were then
      used to generate a potential energy surface by the multiconfiguration Shepard
      interpolation (MCSI) method. The internal rotations in the transition state for
      this reaction (like those in the reactant alcohol) are strongly coupled to each
      other and generate multiple stable conformations, which make important
      contributions to the partition functions. It is shown that neglecting to account
      for the multiple-structure effects and torsional potential anharmonicity effects
      that arise from the torsional modes would lead to order-of-magnitude errors in
      the calculated rate constants at temperatures of interest in combustion.

PMID- 23151031
TI  - Identification of two heterozygous deafness mutations in SLC26A4 (PDS) in a
      Chinese family with two siblings.
AB  - OBJECTIVE: To detect genetic cause of two Chinese siblings (patient 1 and 2) with
      Pendred syndrome. DESIGN: Patients and their parents underwent clinical and
      genetic evaluations. To identify genetic mutations, sequencing of SLC26A4 was
      carried out. STUDY SAMPLE: Two siblings and their parents. RESULTS: Clinical
      evaluations showed that patient 1 suffered from bilateral postlingual progressive
      sensorineural hearing loss with enlarged vestibular aqueduct and slight diffuse
      multinodular goiter with euthyroid, and patient 2 suffered from bilateral
      prelingual progressive sensorineural hearing loss with enlarged vestibular
      aqueduct and no goiter with euthyroid. Furthermore, the sequence analysis of
      SLC26A4 indicated that either of the two siblings presented a compound
      heterozygote for the c.919A>G mutation in the splice site of intron 7 and for the
      c.1548insC mutation in exon 14. Their mother was a heterozygous carrier of the
      splice site mutation in intron 7, and their father was a heterozygous carrier of
      the insertion mutation in exon 14. CONCLUSIONS: Mutation analysis identified a
      compound heterozygous mutation (c.919A>G/c.1548insC) in SLC26A4 in two Chinese
      siblings with Pendred syndrome. Also, c.1548insC was first reported in the
      Chinese population. Although the two siblings from the same family carried the
      same genotype, they presented different phenotypes.

PMID- 23151034
TI  - The tuning fork and the at-risk foot.

PMID- 23151033
TI  - Design of a novel cyclotide-based CXCR4 antagonist with anti-human
      immunodeficiency virus (HIV)-1 activity.
AB  - Herein, we report for the first time the design and synthesis of a novel
      cyclotide able to efficiently inhibit HIV-1 viral replication by selectively
      targeting cytokine receptor CXCR4. This was accomplished by grafting a series of
      topologically modified CVX15 based peptides onto the loop 6 of cyclotide MCoTI-I.
      The most active compound produced in this study was a potent CXCR4 antagonist
      (EC50~20 nM) and an efficient HIV-1 cell-entry blocker (EC50~2 nM). This
      cyclotide also showed high stability in human serum, thereby providing a
      promising lead compound for the design of a novel type of peptide-based
      anticancer and anti-HIV-1 therapeutics.

PMID- 23151038
TI  - Deciphering the chemical bonding in anionic thallium clusters.
AB  - The chemical bonding schemes of thallium cluster anions commonly comply with
      neither Wade-Mingos's rules nor the Zintl-Klemm concept and thus far have escaped
      a fully consistent description. In general, the number of electrons available for
      the cluster skeleton bonding fall below those required according to the
      qualitative concepts mentioned and the clusters were labeled "hypoelectronic".
      Based on fully relativistic band structure calculations on respective complete
      extended solids and electronic structure calculations on excised, charge
      compensated, and geometrically optimized clusters, we have identified two
      mechanisms that are suited to lift the degeneracy of partially filled electronic
      states and to open a HOMO-LUMO gap, the Jahn-Teller effect and relativistic spin
      orbit coupling. Treatment on this level of theory shows that, in accordance with
      experiment, the thallium cluster anions known are electronically saturated and
      not deficient in valence electrons. We provide qualitative group theoretical
      procedures for analyzing the Jahn-Teller effect and spin-orbit coupling in
      lifting the degeneracy of frontier orbitals in highly symmetric thallium cluster
      anions.

PMID- 23151039
TI  - Recombination dynamics of charge pairs in a push-pull polyfluorene-derivative.
AB  - We investigate the properties of long-lived species in F8BT films through time
      resolved photoluminescence (PL) measurements at room temperature and 10 K. The
      kinetics consist of an initial exponential decay (tau = 2.26 ns) followed by a
      weak power-law decay (I(t) [proportionality] t(-1)) up to at least 1 ms, both of
      which depend weakly on temperature. From fluence-dependent PL and ultrafast
      transient absorption (TA) measurements, we confirm that this emission arises from
      the recombination of geminate charge-pairs generated through singlet-singlet
      annihilation. This behavior is a consequence of the donor-acceptor nature of this
      polymer, which enhances singlet-singlet annihilation and facilitates the
      formation of long-lived geminate-pairs from energetic singlet states.

PMID- 23151037
TI  - The acellular myocardial flap: a novel extracellular matrix scaffold enriched
      with patent microvascular networks and biocompatible cell niches.
AB  - There is a great need for acellular, fully vascularized, and biocompatible
      myocardial scaffolds that provide agreeable biological, nutritional, and
      biomechanical niches for reseeded cells for in vitro and in vivo applications. We
      generated myocardial flap scaffolds comprising porcine left-anterior ventricular
      myocardium and its associated coronary arteries and veins and investigated the
      combinatorial effects of sodium dodecyl sulfate (SDS) and sodium hydroxide (NaOH)
      perfusion on both the myocardial extracellular matrix (ECM) and the vascular ECM.
      Results showed that all scaffolds displayed a fully intact and patent
      vasculature, with arterial burst pressures indistinguishable from native coronary
      arteries and perfusion to the level of capillaries. Scaffolds were free of
      cellular proteins and retained collagen and elastin ECM components, exhibited
      excellent mechanical properties, and were cytocompatible toward relevant seeded
      cells. SDS perfusion preserved collagen IV, laminin, and fibronectin well, but
      only reduced DNA content by 33%; however, this was further improved by post-SDS
      nuclease treatments. By comparison, NaOH was very effective in removing cells and
      eliminated more than 95% of tissue DNA, but also significantly reduced levels of
      laminin and fibronectin. Such constructs can be readily trimmed to match the size
      of the infarct and might be able to functionally integrate within host myocardium
      and be nourished by direct anastomotic connection with the host's own
      vasculature; they might also be useful as physiologically accurate models for in
      vitro studies of cardiac physiology and pathology.

PMID- 23151036
TI  - Nitric oxide and superoxide mediate diesel particle effects in cytokine-treated
      mice and murine lung epithelial cells--implications for susceptibility to traffic
      related air pollution.
AB  - BACKGROUND: Epidemiologic studies associate childhood exposure to traffic-related
      air pollution with increased respiratory infections and asthmatic and allergic
      symptoms. The strongest associations between traffic exposure and negative health
      impacts are observed in individuals with respiratory inflammation. We
      hypothesized that interactions between nitric oxide (NO), increased during lung
      inflammatory responses, and reactive oxygen species (ROS), increased as a
      consequence of traffic exposure ? played a key role in the increased
      susceptibility of these at-risk populations to traffic emissions. METHODS: Diesel
      exhaust particles (DEP) were used as surrogates for traffic particles. Murine
      lung epithelial (LA-4) cells and BALB/c mice were treated with a cytokine mixture
      (cytomix: TNFalpha, IL-1beta, and IFNgamma) to induce a generic inflammatory
      state. Cells were exposed to saline or DEP (25 MUg/cm(2)) and examined for
      differential effects on redox balance and cytotoxicity. Likewise, mice undergoing
      nose-only inhalation exposure to air or DEP (2 mg/m(3) * 4 h/d * 2 d) were
      assessed for differential effects on lung inflammation, injury, antioxidant
      levels, and phagocyte ROS production. RESULTS: Cytomix treatment significantly
      increased LA-4 cell NO production though iNOS activation. Cytomix +  DEP-exposed
      cells incurred the greatest intracellular ROS production, with commensurate
      cytotoxicity, as these cells were unable to maintain redox balance. By contrast,
      saline + DEP-exposed cells were able to mount effective antioxidant responses.
      DEP effects were mediated by: (1) increased ROS including superoxide anion
      (O(2)(.-)), related to increased xanthine dehydrogenase expression and reduced
      cytosolic superoxide dismutase activity; and (2) increased peroxynitrite
      generation related to interaction of O(2)(.-) with cytokine-induced NO. Effects
      were partially reduced by superoxide dismutase (SOD) supplementation or by
      blocking iNOS induction. In mice, cytomix +  DEP-exposure resulted in greater ROS
      production in lung phagocytes. Phagocyte and epithelial effects were, by and
      large, prevented by treatment with FeTMPyP, which accelerates peroxynitrite
      catalysis. CONCLUSIONS: During inflammation, due to interactions of NO and O(2)(.
      ), DEP-exposure was associated with nitrosative stress in surface epithelial
      cells and resident lung phagocytes. As these cell types work in concert to
      provide protection against inhaled pathogens and allergens, dysfunction would
      predispose to development of respiratory infection and allergy. Results provide a
      mechanism by which individuals with pre-existing respiratory inflammation are at
      increased risk for exposure to traffic-dominated urban air pollution.

PMID- 23151040
TI  - Cerebrospinal fluid CD19(+)  B-cell expansion in N-methyl-D-aspartate receptor
      encephalitis.
AB  - There is increasing interest in the role of autoantibodies in acquired autoimmune
      central nervous system disorders. N-methyl-D-aspartate receptor (NMDAR)
      encephalitis is an autoimmune encephalitis defined by the presence of
      autoantibodies that bind to the NMDAR. Although there is evidence of NMDAR
      antibody pathogenicity, it is unclear which treatment results in the best
      outcome. We measured the proportion of B-cells in the cerebrospinal fluid of two
      children with NMDAR encephalitis (a 6-year-old male and a 4-year-old female), one
      in the acute phase and one in the relapsing phase. The proportion of CD19(+) B
      cells in both children was greater than 10%, significantly higher than seen in
      non-inflammatory neurological disorders (<1%). This finding supports the use of
      drugs, such as rituximab, that deplete B-cells in severe or refractory cases of
      NMDAR encephalitis, and lends further support to the humoral autoimmune
      hypothesis in NMDAR encephalitis.

PMID- 23151041
TI  - Mild one-step synthesis of dibromo compounds from cyclic ethers.
AB  - A novel one-step method for mildly converting cyclic ethers into dibromo
      compounds is reported. Alcohols, oximes, aldehydes, and ketones are known to
      react under Appel or Corey-Fuchs reaction conditions, but apparently these have
      never been applied to oxetanes or larger cyclic ethers. Treatment of 3,3
      dimethyloxetane (1) with tetrabromomethane and triphenylphosphine gave the
      corresponding dibromo compound 1,3-dibromo-2,2-dimethylpropane (2). The less
      strained homologue oxolane (6) was also reacted giving 1,4-dibromobutane (7) in a
      93% yield. Mechanistic interpretations are offered to explain the observed
      reaction rates of the conversions described.

PMID- 23151042
TI  - Total synthesis of the proposed structure of roxbin B; the nonidentical outcome.
AB  - A proposed structure of roxbin B was synthesized. For the synthesis, a new
      synthetic method for the preparation of the hexahydroxydiphenoyl (HHDP) bridge
      was developed that involved the stepwise esterification of axially chiral HHDP
      acid anhydride. The synthesized compound was not identical to the natural roxbin
      B.

PMID- 23151043
TI  - Chemical analysis of single cells.

PMID- 23151044
TI  - Acute traumatic brain injury: is current management evidence based? An empirical
      analysis of systematic reviews.
AB  - Traumatic brain injury (TBI) is a major health and socioeconomic problem
      worldwide with a high rate of death and long-term disability. Previous studies
      have summarized evidence from large-scale randomized trials, finding no
      intervention showing convincing efficacy for acute TBI management. The present
      empirical study set out to assess another crucial component of evidence base
      systematic review, which contributes a lot to evidence-based health care, in
      terms of clinical issues, methodological aspects, and implication for practice
      and research. A total of 44 systematic reviews pertaining to therapeutic
      interventions for acute TBI were identified through electronic database
      searching, clinical guideline retrieval, and expert consultation, of which 21
      were published in Cochrane Library and 23 in peer-reviewed journals. Their
      methodological quality was generally satisfactory, with the median Overview
      Quality Assessment Questionnaire score of 5.5 (interquartile range 2-7). Cochrane
      reviews are of better quality than regular journal reviews. Twenty-nine high
      quality reviews provided no conclusive evidence for the investigated 22
      interventions except for an adverse effect of corticosteroids. Less than one
      third of the component trials were reported with adequate allocation concealment.
      Additionally other methodological flaws in design-for example, ignoring
      heterogeneity among the TBI population-also contributed to the failure of past
      clinical research. Based on the above findings, evidence from both systematic
      reviews and clinical trials does not fully support current management of acute
      TBI. Translating from laboratory success to clinical effect remains an unique
      challenge. Accordingly it may be the time to rethink the way in future practice
      and clinical research in TBI.

PMID- 23151045
TI  - MMpred: functional miRNA--mRNA interaction analyses by miRNA expression
      prediction.
AB  - BACKGROUND: MicroRNA (miRNA) directed gene repression is an important mechanism
      of posttranscriptional regulation. Comprehensive analyses of how microRNA
      influence biological processes requires paired miRNA-mRNA expression datasets.
      However, a review of both GEO and ArrayExpress repositories revealed few such
      datasets, which was in stark contrast to the large number of messenger RNA (mRNA)
      only datasets. It is of interest that numerous primary miRNAs (precursors of
      microRNA) are known to be co-expressed with coding genes (host genes). RESULTS:
      We developed a miRNA-mRNA interaction analyses pipeline. The proposed solution is
      based on two miRNA expression prediction methods - a scaling function and a
      linear model. Additionally, miRNA-mRNA anti-correlation analyses are used to
      determine the most probable miRNA gene targets (i.e. the differentially expressed
      genes under the influence of up- or down-regulated microRNA). Both the
      consistency and accuracy of the prediction method is ensured by the application
      of stringent statistical methods. Finally, the predicted targets are subjected to
      functional enrichment analyses including GO, KEGG and DO, to better understand
      the predicted interactions. CONCLUSIONS: The MMpred pipeline requires only mRNA
      expression data as input and is independent of third party miRNA target
      prediction methods. The method passed extensive numerical validation based on the
      binding energy between the mature miRNA and 3' UTR region of the target gene. We
      report that MMpred is capable of generating results similar to that obtained
      using paired datasets. For the reported test cases we generated consistent output
      and predicted biological relationships that will help formulate further testable
      hypotheses.

PMID- 23151046
TI  - Retreatment with bendamustine-containing regimens in patients with
      relapsed/refractory chronic lymphocytic leukemia and indolent B-cell lymphomas
      achieves high response rates and some long lasting remissions.
AB  - Bendamustine and bendamustine/rituximab combinations have shown high efficacy in
      relapsed/refractory chronic lymphocytic leukemia (CLL) and indolent B-cell
      malignancies (non-Hodgkin lymphoma, NHL). No data exist about bendamustine
      retreatment after relapse, concerning efficacy and toxicity in this patient
      population. Eighty-eight outpatients (57 patients with CLL, 31 patients with NHL)
      who had previously been treated with bendamustine were retreated with a
      bendamustine regimen. Treatment consisted of bendamustine (B) or bendamustine +
      mitoxantrone (BM) or bendamustine + rituximab (BR) or bendamustine + mitoxantrone
      + rituximab (BMR). Median age was 72 years (50-88). A reversible grade 3 or 4
      leukocytopenia or thrombocytopenia was observed in 24% and 13%, respectively. The
      overall response rate (ORR) was 76% (7% complete remission [CR], 69% partial
      remission [PR]) with 77% (6% CR, 71% PR) in CLL and 71% (8% CR, 63% PR) in NHL.
      ORR according to regimen was as follows: B: 57% (14% CR, 43% PR), BM: 70% (4% CR,
      66% PR), BR: 55% (10% CR, 45% PR), BMR: 84% (7% CR, 78% PR). Bendamustine
      retreatment is feasible and achieves high response rates and some long lasting
      remissions.

PMID- 23151047
TI  - Red/green cyanobacteriochromes: sensors of color and power.
AB  - Phytochromes are red/far-red photoreceptors using cysteine-linked linear
      tetrapyrrole (bilin) chromophores to regulate biological responses to light.
      Light absorption triggers photoisomerization of the bilin between the 15Z and 15E
      photostates. The related cyanobacteriochromes (CBCRs) extend the photosensory
      range of the phytochrome superfamily to shorter wavelengths of visible light.
      Several subfamilies of CBCRs have been described. Representatives of one such
      subfamily, including AnPixJ and NpR6012g4, exhibit red/green photocycles in which
      the 15Z photostate is red-absorbing like that of phytochrome but the 15E
      photoproduct is instead green-absorbing. Using recombinant expression of
      individual CBCR domains in Escherichia coli, we fully survey the red/green
      subfamily from the cyanobacterium Nostoc punctiforme. In addition to 14 new
      photoswitching CBCRs, one apparently photochemically inactive protein exhibiting
      intense red fluorescence was observed. We describe a novel orange/green
      photocycle in one of these CBCRs, NpF2164g7. Dark reversion varied in this panel
      of CBCRs; some examples were stable as the 15E photoproduct for days, while
      others reverted to the 15Z dark state in minutes or even seconds. In the case of
      NpF2164g7, dark reversion was so rapid that reverse photoconversion of the green
      absorbing photoproduct was not significant in restoring the dark state, resulting
      in a broadband response to light. Our results demonstrate that red/green CBCRs
      can thus act as sensors for the color or intensity of the ambient light
      environment.

PMID- 23151048
TI  - Trop-2 protein overexpression is an independent marker for predicting disease
      recurrence in endometrioid endometrial carcinoma.
AB  - BACKGROUND: Endometrial cancer is the most common gynecologic malignancy in
      developed countries. Trop-2 is a glycoprotein involved in cellular signal
      transduction and is differentially overexpressed relative to normal tissue in a
      variety of human adenocarcinomas, including endometrioid endometrial carcinomas
      (EEC). Trop-2 overexpression has been proposed as a marker for biologically
      aggressive tumor phenotypes. METHODS: Trop-2 protein expression was quantified
      using tissue microarrays consisting of formalin-fixed paraffin-embedded specimens
      from 118 patients who underwent surgical staging from 2001-9 by laparotomy for
      EEC. Clinicopathologic characteristics including age, stage, grade,
      lymphovascular space invasion, and medical comorbidities were correlated with
      immunostaining score. Univariate and multivariate analyses were performed for
      overall survival, disease-free survival, and progression-free survival in
      relation to clinical parameters and Trop-2 protein expression. RESULTS: Clinical
      outcome data were available for 103 patients. Strong Trop-2 immunostaining was
      significantly associated with higher tumor grade (p=0.02) and cervical
      involvement (p<0.01). Univariate analyses showed a significant association with
      reduced disease-free survival (DFS) (p=0.01), and a trend towards significance
      for overall and progression-free survival (p=0.06 and p=0.05, respectively).
      Multivariate analyses revealed Trop-2 overexpression and advanced FIGO stage to
      be independent prognostic factors for poor DFS (p=0.04 and p <0.001,
      respectively). CONCLUSIONS: Trop-2 protein overexpression is significantly
      associated with higher tumor grade and serves as an independent prognostic factor
      for DFS in endometrioid endometrial cancer.

PMID- 23151050
TI  - Photochemical and photophysical properties of sequentially functionalized
      fullerenes in the aqueous phase.
AB  - The vast range of C60 derivatives makes it difficult to assess the potential
      environmental impact of this class of materials, while past environmental studies
      mostly focused only on pristine C60. Central to derivatized C60's potential to
      negatively impact (micro)biological receptors upon unintended release is its
      unique property of mediating the transfer of light energy to ambient oxygen,
      producing 1O2. To initiate the process of establishing a thorough understanding
      of the photoinduced adverse biological effects of functionalized fullerenes and
      their aqueous dispersions, the photochemical properties relevant to 1O2
      production were evaluated using three selected series of mono-, bis-, and tris
      adducted fullerene materials. Differential 1O2 production of derivatives in
      toluene were explained by spectral variations under visible and UVA light
      conditions. Of the nine functionalities studied only aggregates of two positively
      charged derivatives showed significant photoactivity under experimental
      conditions. Laser flash photolysis revealed a triplet excited state in the
      photoactive aggregates with a sufficiently long lifetime to be quenched by 3O2.
      Dynamic light scattering, transmission electron microscopy, and electron
      diffraction patterns revealed aggregates with sizes typical of aqueous C60
      colloids that varied in crystallinity based on functionality. Results raised
      questions about our current understanding of the photoactivity of fullerene
      aggregates.

PMID- 23151049
TI  - A mechanical model for predicting the probability of osteoporotic hip fractures
      based in DXA measurements and finite element simulation.
AB  - BACKGROUND: Osteoporotic hip fractures represent major cause of disability, loss
      of quality of life and even mortality among the elderly population. Decisions on
      drug therapy are based on the assessment of risk factors for fracture, from BMD
      measurements. The combination of biomechanical models with clinical studies could
      better estimate bone strength and supporting the specialists in their decision.
      METHODS: A model to assess the probability of fracture, based on the Damage and
      Fracture Mechanics has been developed, evaluating the mechanical magnitudes
      involved in the fracture process from clinical BMD measurements. The model is
      intended for simulating the degenerative process in the skeleton, with the
      consequent lost of bone mass and hence the decrease of its mechanical resistance
      which enables the fracture due to different traumatisms. Clinical studies were
      chosen, both in non-treatment conditions and receiving drug therapy, and fitted
      to specific patients according their actual BMD measures. The predictive model is
      applied in a FE simulation of the proximal femur. The fracture zone would be
      determined according loading scenario (sideway fall, impact, accidental loads,
      etc.), using the mechanical properties of bone obtained from the evolutionary
      model corresponding to the considered time. RESULTS: BMD evolution in untreated
      patients and in those under different treatments was analyzed. Evolutionary
      curves of fracture probability were obtained from the evolution of mechanical
      damage. The evolutionary curve of the untreated group of patients presented a
      marked increase of the fracture probability, while the curves of patients under
      drug treatment showed variable decreased risks, depending on the therapy type.
      CONCLUSION: The FE model allowed to obtain detailed maps of damage and fracture
      probability, identifying high-risk local zones at femoral neck and
      intertrochanteric and subtrochanteric areas, which are the typical locations of
      osteoporotic hip fractures.The developed model is suitable for being used in
      individualized cases. The model might better identify at-risk individuals in
      early stages of osteoporosis and might be helpful for treatment decisions.

PMID- 23151051
TI  - The clinical usefulness of nuclear matrix protein-22 in patients with end-stage
      renal disease and microscopic hematuria.
AB  - OBJECTIVES: To evaluate the sensitivity, specificity, and false-positive rate of
      the nuclear matrix protein-22 (NMP22) test in patients with end-stage renal
      disease (ESRD) and microscopic hematuria in order to avoid unnecessary follow-up
      tests for patients with false-positive NMP22 test results. PATIENTS AND METHODS:
      Patients with ESRD were screened for microscopic hematuria as part of the pre
      transplant workup. Patients with documented microscopic hematuria underwent
      workup as recommended by the American Urological Association. RESULTS: Between
      January 2006 and April 2012, 277 patients with ESRD were referred to the
      Department of Urology for pre-transplant evaluation. Fifty-seven (22.6%) patients
      were found to have microscopic hematuria and underwent further testing. Nineteen
      (33.3%) patients demonstrated a positive NMP22 test result and 38 (66.7%) had a
      negative NMP22 test result. The false-positive rate was 32.7%. The sensitivity
      and specificity of the NMP22 test in this patient population were 50% and 67%,
      respectively. The positive predictive value of the test was 52.6% and the
      negative predictive value 97.3%. Especially noteworthy, the two detected
      transitional cell cancers of the urinary bladder were both demonstrated during
      cystoscopy, independent of their NMP22 or urine cytology test result.
      CONCLUSIONS: Our study revealed a significantly increased NMP22 test false
      positive rate, low sensitivity, and specificity in the setting of high prevalence
      of microscopic hematuria, proteinuria, and low glomerular filtration rate in
      patients with ESRD. Therefore, cystoscopy remains the gold standard for patients
      with ESRD and microscopic hematuria for pre-transplant evaluation.

PMID- 23151052
TI  - Leucocytosis and thrombosis at diagnosis are associated with poor survival in
      polycythaemia vera: a population-based study of 327 patients.
AB  - Three hundred and twenty-seven patients from two population-based cohorts with an
      established diagnosis of polycythaemia vera were studied for prognostic risk
      factors for survival and leukaemia in a long-term survey. The relative survival
      (RS) was 72% and 46% at 10 and 20 years respectively, from the time of diagnosis.
      Multivariate analysis identified age >70 years, white blood cell count >13 *
      10(9) /l and thrombo-embolism at diagnosis as independent risk factors. Patients
      with two or three of these factors had a 10 year RS of 26%, compared with 59% and
      84% in patients with one and no risk factors, respectively. Age and leucocyte
      count are the main predicting factors for survival in polycythaemia vera.

PMID- 23151053
TI  - Identifying specific non-attending groups in breast cancer screening--population
      based registry study of participation and socio-demography.
AB  - BACKGROUND: A population-based breast cancer screening programme was implemented
      in the Central Denmark Region in 2008-09. The objective of this registry-based
      study was to examine the association between socio-demographic characteristics
      and screening participation and to examine whether the group of non-participants
      can be regarded as a homogeneous group of women. METHOD: Participation status was
      obtained from a regional database for all women invited to the first screening
      round in the Central Denmark Region in 2008-2009 (n=149,234). Participation data
      was linked to registries containing socio-demographic information. Distance to
      screening site was calculated using ArcGIS. Participation was divided into
      'participants' and 'non-participants', and non-participants were further
      stratified into 'active non-participants' and 'passive non-participants' based on
      whether the woman called and cancelled her participation or was a 'no-show'.
      RESULTS: The screening participation rate was 78.9%. In multivariate analyses,
      non-participation was associated with older age, immigrant status, low OECD
      adjusted household income, high and low level education compared with middle
      level education, unemployment, being unmarried, distance to screening site >20
      km, being a tenant and no access to a vehicle. Active and passive non
      participants comprised two distinct groups with different socio-demographic
      characteristics, with passive non-participants being more socially deprived
      compared with active non-participants. CONCLUSION: Non-participation was
      associated with low social status e.g. low income, unemployment, no access to
      vehicle and status as tenant. Non-participants were also more likely than
      participants to be older, single, and of non-Danish origin. Compared to active
      non-participants, passive non-participants were characterized by e.g. lower
      income and lower educational level. Different interventions might be warranted to
      increase participation in the two non-participant groups.

PMID- 23151054
TI  - Rational design of highly selective spleen tyrosine kinase inhibitors.
AB  - A novel approach to design selective spleen tyrosine kinase (Syk) inhibitors is
      described. Inhibition of spleen tyrosine kinase has attracted much attention as a
      mechanism for the treatment of autoimmune diseases such as asthma, rheumatoid
      arthritis, and SLE. Fostamatinib, a Syk inhibitor that successfully completed
      phase II clinical trials, also exhibits some undesirable side effects. More
      selective Syk inhibitors could offer safer, alternative treatments. Through a
      systematic evaluation of the kinome, we identified Pro455 and Asn457 in the Syk
      ATP binding site as a rare combination among sequence aligned kinases and
      hypothesized that optimizing the interaction between them and a Syk inhibitor
      molecule would impart high selectivity for Syk over other kinases. We report the
      structure-guided identification of three series of selective spleen tyrosine
      kinase inhibitors that support our hypothesis and offer useful guidance to other
      researchers in the field.

PMID- 23151055
TI  - Normal values of aortic dimensions, distensibility, and pulse wave velocity in
      children and young adults: a cross-sectional study.
AB  - BACKGROUND: Aortic enlargement and impaired bioelasticity are of interest in
      several cardiac and non-cardiac diseases as they can lead to cardiovascular
      complications. Cardiovascular magnetic resonance (CMR) is increasingly accepted
      as a noninvasive tool in cardiovascular evaluation. Assessment of aortic anatomy
      and bioelasticity, namely aortic distensibility and pulse wave velocity (PWV), by
      CMR is accurate and reproducible and could help to identify anatomical and
      bioelastic abnormalities of the aorta. However, normal CMR values for healthy
      children and young adults are lacking. METHODS: Seventy-one heart-healthy
      subjects (age 16.4 +/- 7.6 years, range 2.3-28.3 years) were examined using a 3.0
      Tesla CMR scanner. Aortic cross-sectional areas and aortic distensibility were
      measured at four positions of the ascending and descending thoracic aorta. PWV
      was assessed from aortic blood flow velocity measurements in a aortic segment
      between the ascending aorta and the proximal descending aorta. The Lambda-Mu
      Sigma (LMS) method was used to obtain percentile curves for aortic cross
      sectional areas, aortic distensibility and PWV according to age. RESULTS: Aortic
      areas, PWV and aortic distensibility (aortic cross-sectional areas: r = 0.8 to
      0.9, p < 0.001; PWV: r = 0.25 to 0.32, p = 0.047 to 0.009; aortic distensibility
      r = -0.43 to -0.62, p < 0.001) correlated with height, weight, body surface area,
      and age. There were no significant sex differences. CONCLUSIONS: This study
      provides percentile curves for cross-sectional areas, distensibility and pulse
      wave velocity of the thoracic aorta in children and young adolescents between
      their 3rd and 29th year of life. These data may serve as a reference for the
      detection of pathological changes of the aorta in cardiovascular disease.

PMID- 23151056
TI  - Aedes albopictus in Lebanon, a potential risk of arboviruses outbreak.
AB  - BACKGROUND: The mosquito Aedes albopictus is undergoing a worldwide expansion
      with potential consequences on transmission of various arboviruses. This species
      has been first detected in Lebanon in 2003. METHODS: We performed a phylogenetic
      study of Lebanese specimens and assessed their host preference by detecting
      human, cat, dog and chicken immunoglobulins in mosquito blood-meals. Their
      capacity to transmit arboviruses was investigated by providing infectious blood
      meals using an artificial feeding system followed by detection of viral particles
      in mosquito saliva. RESULTS: Our results suggest that Lebanese strains are part
      of the recent wave of Ae. albopictus expansion and are related to some European,
      African and North American strains. They exhibited a host preference towards
      humans and an important capacity to transmit arboviruses. Indeed, we showed that
      Ae. albopictus was able to transmit chikungunya (CHIKV), dengue (DENV) and West
      Nile (WNV) viruses. At day 10 after an infectious blood-meal at a titer of 108
      MID50/ml, 30% of mosquitoes delivered an average of 515 +/- 781 viral particles
      of CHIKV in saliva collected using a forced salivation technique and 55% with an
      average of 245 +/- 304 viral particles when infected with WNV. Whereas DENV was
      not found in saliva at day 10 post-infection (pi), an average of 174 +/- 455
      viral particles was detected in 38.1% of mosquitoes tested at day 21 after an
      infectious blood-meal at a higher titer of 109 MID50/ml. CONCLUSION: These
      observations suggest that Ae. albopictus around Beirut is a potential vector of
      the three tested arboviruses.

PMID- 23151057
TI  - Serum transaminase elevation in children with rotavirus gastroenteritis: seven
      years' experience.
AB  - BACKGROUND: There are no studies on clinically significant transaminase elevation
      due to rotavirus gastroenteritis in the literature. Also, there are significant
      discrepancies among previous studies regarding the prevalence of increased serum
      transaminase levels in rotavirus infection. METHODS: Patients investigated for
      rotavirus by stool antigen testing, who were followed between January 2005 and
      May 2012, were retrospectively enrolled in this study. Patients were divided into
      2 groups according to their rotavirus results: rotavirus-positive acute
      gastroenteritis (RPAG) and rotavirus-negative acute gastroenteritis (RNAG)
      groups. RESULTS: A total of 4317 children who presented with acute
      gastroenteritis were assessed. The study was completed with 642 patients who met
      the inclusion criteria. In the RPAG group (n = 272), elevated alanine
      aminotransferase (ALT) was found in 42 (15.4%) patients and elevated aspartate
      aminotransferase (AST) in 69 (25.4%), while in the RNAG group (n = 370), these
      numbers were 25 (6.8%) and 44 (11.9%), respectively. The elevated ALT and AST
      levels were found to be significantly higher in the RPAG group than in the RNAG
      group (both p < 0.001). The prevalence of elevated transaminase levels was found
      to be similar with respect to gastroenteritis severity score (p > 0.05). The high
      serum transaminase levels normalized uneventfully in all patients in the RPAG and
      RNAG groups during follow-up. CONCLUSIONS: In this study, our results clearly
      signify a liver influence in rotavirus infections. Therefore, rotavirus
      infections should be kept in mind when evaluating the aetiology of transaminase
      elevation in patients with acute gastroenteritis.

PMID- 23151058
TI  - Moxifloxacin-associated neutropenia.
AB  - A 32-y-old woman presented with pneumonia. Treatment was started with
      moxifloxacin. On day 2 of moxifloxacin treatment the patient developed
      neutropenia. After discontinuing the moxifloxacin, neutrophil counts were normal
      on day 4. Clinicians should be aware of the possibility of this adverse effect in
      patients treated with moxifloxacin.

PMID- 23151059
TI  - Variational calculations of vibrational energies and IR spectra of trans- and cis
      HOCO using new ab initio potential energy and dipole moment surfaces.
AB  - We report ab initio potential energy and dipole moment surfaces that span the
      regions describing the minima of trans- and cis-HOCO and the barrier separating
      them. We use the new potential in three types of variational calculations of the
      vibrational eigenstates, for zero total angular momentum. Two use the code
      MULTIMODE (MM) in the so-called single-reference and reaction path versions. The
      third uses the exact Hamiltonian in diatom-diatom Jacobi coordinates. The single
      reference version of MM is limited to a description of states that are localized
      at each minimum separately, whereas the reaction-path version and the Jacobi
      approach describe localized and delocalized states. The vibrational IR spectrum
      for zero total angular momentum is also reported for the trans and cis
      fundamentals and selected overtone and combination states with significant
      oscillator strength. 

PMID- 23151060
TI  - Respiratory and sleep disorders in female children with atypical Rett syndrome
      caused by mutations in the CDKL5 gene.
AB  - AIM: In female children with drug-resistant seizures and developmental delay from
      birth, atypical Rett syndrome caused by mutations in the CDKL5 gene should be
      considered. Several clinical features resemble classic Rett syndrome. Respiratory
      and sleep abnormalities are frequently present in Rett syndrome, whereas little
      is known in patients with CDKL5 mutations. METHOD: In four genetically confirmed
      female patients with CDKL5 mutations (age range 2-15 y), the presence of
      breathing and sleep abnormalities was evaluated using the validated Sleep
      Disturbance Scale for Children and polysomnography (PSG). RESULTS: The Sleep
      Disturbance Scale for Children indicated disorders of initiating and maintaining
      sleep, daytime somnolence, and sleep breathing disorders. In one patient, PSG
      showed central apnoeas during sleep: her total apnoea-hypopnoea index (AHI) was
      4.9, of which the central AHI was 3.4/h. When awake, central apnoeas were present
      in two of the four female children (central AHI 28/h and 41/h respectively), all
      preceded by hyperventilation. PSG showed low rapid eye movement (REM) sleep (9.7
      18.3%), frequent awakenings, and low sleep efficiency (range 59-78%).
      INTERPRETATION: Episodic hyperventilation followed by central apnoeas was present
      while awake in two of four patients. This may indicate failure of brainstem
      respiratory centres. In addition, low REM sleep, frequent arousals (not caused by
      apnoeas/seizures), and low sleep efficiency were present. Similar to Rett
      syndrome, in patients with CDKL5 mutations PSG seems warranted to evaluate
      breathing and sleep disturbances.

PMID- 23151061
TI  - Efficient 2-aryl benzothiazole formation from aryl ketones and 2
      aminobenzenethiols under metal-free conditions.
AB  - 2-Aryl benzothiazole formation from aryl ketones and 2-aminobenzenethiols under
      metal- and I(2)-free conditions was described. Various 2-aryl benzothiazoles were
      selectively obtained in good yields using molecular oxygen as oxidant. DMSO
      played an important role in this transformation. Functional groups such as
      methyl, methoxy, fluoro, chloro, bromo and nitro groups were tolerated under the
      optimized reaction conditions.

PMID- 23151062
TI  - A solid state density functional study of crystalline thiophene-based oligomers
      and polymers.
AB  - We present the results of a molecular modeling study of several thiophene-based
      oligomers and polymers by solid state density functional theory (DFT)
      calculations. In particular, we consider two polymers for which limit-ordered
      crystal structures have been reported by our group, on the basis of powder X-ray
      data analysis: poly(3-(S)-2-methylbutylthiophene) (P3MBT) and forms I' and II of
      poly(3-butylthiophene) (P3BT). The calculations employing the functional by
      Perdew and Wang (PWC) in conjunction with the double-zeta polarized numerical
      basis set (DNP) demonstrate that a standard quantum mechanical (QM) approach for
      solid phases can provide a balanced description of the overall structure and
      energetics of thiophene-based oligomers and polymers maintaining a moderate
      computational cost. In addition, the results compare well with those provided by
      specific force field parametrization developed by our group. In many cases,
      PWC/DNP models show even closer agreement with experimental crystal structures,
      making it the method of choice for computationally accessible problems. Finally,
      solid state DFT minimizations confirm that the reported crystal structures of
      P3MBT and P3BT correspond to well-defined energy minima.

PMID- 23151063
TI  - Powerful binders for the D-dimer by conjugation of the GPRP peptide to
      polypeptides from a designed set--illustrating a general route to new binders for
      proteins.
AB  - The synthetic tetrapeptide GPRP based on the amino-terminal GPR sequence of the
      fibrin alpha-chain binds the D-dimer protein with a dissociation constant K(D) of
      25 MUM. The D-dimer protein, a well-known biomarker for thrombosis, contains two
      cross-linked D fragments from the fibrinogen protein formed upon degradation of
      the fibrin gel, the core component of blood clots. In order to develop a specific
      high-affinity binder for the D-dimer protein, GPRP was conjugated via an
      aliphatic spacer to each member of a set of sixteen polypeptides designed for the
      development of binder molecules for proteins in general. The binders were
      individually characterized and ranked using surface plasmon resonance (SPR)
      analysis. The dissociation constant of the complex formed from the D-dimer and 4
      D15L8-GPRP labeled with fluorescein was determined by fluorescense titration and
      found to be 3 nM, an affinity 4 orders of magnitude higher than that of free
      GPRP. According to SPR analysis, binding was completely inhibited by free GPRP at
      mM concentrations and the polypeptide conjugate was therefore shown to bind
      specifically to the binding site of GPRP. Affinities were further enhanced by
      dimerization of the polypeptide conjugates via a bifunctional linker resulting in
      dissociation constants that were further decreased (affinities increased) by
      factors of 2-4. The results suggest an efficient route to specific binders for
      proteins based on short peptides with affinities that need only to be modest,
      thus shortening the time of binder development dramatically.

PMID- 23151064
TI  - Glycoluril dimer isomerization under aqueous acidic conditions related to
      cucurbituril formation.
AB  - A water-soluble methylene-bridged glycoluril dimer 2S was isolated. It was shown
      that 2S is the only kinetic product of the reaction between glycoluril derivative
      1 and paraformaldehyde. Compound 2S is subsequently intermolecularly transformed
      into its diastereomer 2C. The kinetics and thermodynamics of the S- to C-shaped
      dimer isomerization were investigated under reaction conditions similar to those
      for cucurbituril synthesis.

PMID- 23151065
TI  - Microscopic rates of peptide-phospholipid bilayer interactions from single
      molecule residence times.
AB  - The binding of glucagon-like peptide-1 (GLP-1) to a planar phospholipid bilayer
      is measured using single-molecule total internal reflection fluorescence
      microscopy. From several reports in the literature, GLP-1 has been shown to be a
      random coil in free solution, adopting a folded, alpha-helix conformation when
      intercalated into membrane environments. Single-molecule fluorescence
      measurements of GLP-1 binding to supported lipid bilayers show evidence of two
      populations of membrane-associated molecules having different residence times,
      suggesting weakly adsorbed peptides and strongly bound peptides in the lipid
      bilayer. The path to and from a strongly bound (folded, intercalated) state would
      likely include an adsorbed state as an intermediate, so that the resulting
      kinetics would correspond to a consecutive first-order reversible three-state
      model. In this work, the relationships between measured single-molecule residence
      times and the microscopic rates in a three-state kinetic model are derived and
      used to interpret the binding of GLP-1 to a supported lipid bilayer. The system
      of differential equations associated with the proposed consecutive-three state
      kinetics scheme is solved, and the solution is applied to interpret histograms of
      single-molecule, GLP-1 residence times in terms of the microscopic rates in the
      sequential two-step model. These microscopic rates are used to estimate the free
      energy barrier to adsorption, the fraction of peptides adsorbing to the membrane
      surface that successfully intercalate in the bilayer, the lifetime of inserted
      peptides in the membrane, and the free energy change of insertion into the lipid
      bilayer from the adsorbed state. The transition from a random coil in solution to
      a folded state in a membrane has been recognized as a common motif for insertion
      of membrane active peptides. Therefore, the relationships developed here could
      have wide application to the kinetic analysis of peptide-membrane interactions.

PMID- 23151066
TI  - Strategy to enhance the wettability of bioacive paper-based sensors.
AB  - This paper reports a potential method that can restore the wettability of
      bioactive paper-based sensors while maintaining their bioactivity. This study is
      driven by the need to increase the wettability of the antibody-loaded blood
      typing paper devices in order to increase the blood typing assaying speed using
      such paper devices. Plasma treatment is used to improve the wettability of
      bioactive paper; the protective effect of bovine serum albumin (BSA) to
      biomolecules against plasma deactivation is investigated. In the first stage,
      horseradish peroxidase (HRP) was used as a model biomolecule, because of the
      convenience of its quantifiable colorimetric reaction with a substrate. By using
      this protection approach, the inactivation of biomolecules on paper during the
      plasma treatment is significantly slowed down. This approach enables plasma
      treatment to be used for fabricating paper-based bioactive sensors to achieve
      strong wettability for rapid penetration of liquid samples or reagents. Finally,
      we demonstrate the use of plasma treatment to increase the wettability of
      antibody treated blood typing paper. After the treatment, the blood typing paper
      becomes highly wettable; it allows much faster penetration of blood samples into
      the plasma treated testing paper. Antibodies on the paper are still sufficiently
      active for blood typing and can report patients' blood type accurately.

PMID- 23151067
TI  - Selective inhibition of alpha/beta-hydrolase domain 6 attenuates
      neurodegeneration, alleviates blood brain barrier breakdown, and improves
      functional recovery in a mouse model of traumatic brain injury.
AB  - 2-arachidonylglycerol (2-AG) is the most abundant endocannabinoid in the central
      nervous system and is elevated after brain injury. Because of its rapid
      hydrolysis, however, the compensatory and neuroprotective effect of 2-AG is short
      lived. Although inhibition of monoacylglycerol lipase, a principal enzyme for 2
      AG degradation, causes a robust increase of brain levels of 2-AG, it also leads
      to cannabinoid receptor desensitization and behavioral tolerance. Alpha/beta
      hydrolase domain 6 (ABHD6) is a novel 2-AG hydrolytic enzyme that accounts for a
      small portion of 2-AG hydrolysis, but its inhibition is believed to elevate the
      levels of 2-AG within the therapeutic window without causing side effect. Using a
      mouse model of traumatic brain injury (TBI), we found that post-insult chronic
      treatment with a selective ABHD6 inhibitor WWL70 improved motor coordination and
      working memory performance. WWL70 treatment reduced lesion volume in the cortex
      and neurodegeneration in the dendate gyrus. It also suppressed the expression of
      inducible nitric oxide synthase and cyclooxygenase-2 and enhanced the expression
      of arginase-1 in the ipsilateral cortex at 3 and 7 days post-TBI, suggesting
      microglia/macrophages shifted from M1 to M2 phenotypes after treatment. The blood
      brain barrier dysfunction at 3 and 7 days post-TBI was dramatically reduced.
      Furthermore, the beneficial effects of WWL70 involved up-regulation and
      activation of cannabinoid type 1 and type 2 receptors and were attributable to
      the phosphorylation of the extracellular signal regulated kinase and the
      serine/threonine protein kinase AKT. This study indicates that the fine-tuning of
      2-AG signaling by modulating ABHD6 activity can exert anti-inflammatory and
      neuroprotective effects in TBI.

PMID- 23151068
TI  - Gender differences in predictors of self-rated health in Armenia: a population
      based study of an economy in transition.
AB  - INTRODUCTION: Self-rated health is a widely used health outcome measure that
      strongly correlates with physical and mental health status and predicts
      mortality. This study identified the set of predictors of fair/poor self-rated
      health in adult female and male populations of Armenia during a period of long
      lasting socio-economic transition to a market economy. METHODS: Differences in
      self-rated health were analyzed along three dimensions: socioeconomic,
      behavioral/attitudinal, and psychosocial. The study utilized data from a 2006
      nationwide household health survey that used a multi-stage probability
      proportional to size cluster sampling with a combination of interviewer
      administered and self-administered surveys. Both female and male representatives
      of a household aged 18 and over completed the self-administered survey.
      Multivariate odds ratios (OR) for fair/poor self-rated health were calculated for
      different sets of variables and logistic regression models fitted separately for
      women and men to identify the determinants of fair/poor self-rated health.
      RESULTS: Overall, 2310 women and 462 men participated in the survey. The rate of
      fair/poor self-rated health was 61.8% among women and 59.7% among men. For women,
      the set of independent predictors of fair/poor self-rated health included age,
      unemployment, poverty, low affordability of healthcare, depression, and weak
      social support. For men, the set included age, lower education, depression, weak
      social support, and drinking alcohol less than once a week. For both genders,
      depression and weak social support demonstrated the strongest independent
      association with fair/poor self-rated health. CONCLUSIONS: The prevalence of
      fair/poor self-rated health was similar among men and women in this study, but
      the sets of independent predictors of perceived health differed somewhat,
      possibly, reflecting lifestyle differences between men and women in Armenia.
      Nevertheless, psychosocial variables were the strongest predictors of fair/poor
      self-rated health for both genders, indicating the importance of improving the
      country's psychosocial environment through social reforms and poverty reduction.

PMID- 23151069
TI  - Live virus-free or die: coupling of antivirus immunity and programmed suicide or
      dormancy in prokaryotes.
AB  - BACKGROUND: The virus-host arms race is a major theater for evolutionary
      innovation. Archaea and bacteria have evolved diverse, elaborate antivirus
      defense systems that function on two general principles: i) immune systems that
      discriminate self DNA from nonself DNA and specifically destroy the foreign, in
      particular viral, genomes, whereas the host genome is protected, or ii)
      programmed cell suicide or dormancy induced by infection. PRESENTATION OF THE
      HYPOTHESIS: Almost all genomic loci encoding immunity systems such as CRISPR-Cas,
      restriction-modification and DNA phosphorothioation also encompass suicide genes,
      in particular those encoding known and predicted toxin nucleases, which do not
      appear to be directly involved in immunity. In contrast, the immunity systems do
      not appear to encode antitoxins found in typical toxin-antitoxin systems. This
      raises the possibility that components of the immunity system themselves act as
      reversible inhibitors of the associated toxin proteins or domains as has been
      demonstrated for the Escherichia coli anticodon nuclease PrrC that interacts with
      the PrrI restriction-modification system. We hypothesize that coupling of diverse
      immunity and suicide/dormancy systems in prokaryotes evolved under selective
      pressure to provide robustness to the antivirus response. We further propose that
      the involvement of suicide/dormancy systems in the coupled antivirus response
      could take two distinct forms:1) induction of a dormancy-like state in the
      infected cell to 'buy time' for activation of adaptive immunity; 2) suicide or
      dormancy as the final recourse to prevent viral spread triggered by the failure
      of immunity. TESTING THE HYPOTHESIS: This hypothesis entails many experimentally
      testable predictions. Specifically, we predict that Cas2 protein present in all
      cas operons is a mRNA-cleaving nuclease (interferase) that might be activated at
      an early stage of virus infection to enable incorporation of virus-specific
      spacers into the CRISPR locus or to trigger cell suicide when the immune function
      of CRISPR-Cas systems fails. Similarly, toxin-like activity is predicted for
      components of numerous other defense loci. IMPLICATIONS OF THE HYPOTHESIS: The
      hypothesis implies that antivirus response in prokaryotes involves key decision
      making steps at which the cell chooses the path to follow by sensing the course
      of virus infection. REVIEWERS: This article was reviewed by Arcady Mushegian,
      Etienne Joly and Nick Grishin. For complete reviews, go to the Reviewers' reports
      section.

PMID- 23151070
TI  - Measuring uptake dynamics of multiple identifiable carbon nanotube species via
      high-speed confocal Raman imaging of live cells.
AB  - Carbon nanotube uptake was measured via high-speed confocal Raman imaging in live
      cells. Spatial and temporal tracking of two cell-intrinsic and nine nanotube
      derived Raman bands was conducted simultaneously in RAW 264.7 macrophages. Movies
      resolved single (n, m) species, defects, and aggregation states of nanotubes
      transiently as well as the cell position, denoted by lipid and protein signals.
      This work portends the real-time molecular imaging of live cells and tissues
      using Raman spectroscopy, affording multiplexing and complete photostability.

PMID- 23151071
TI  - Incidence, clinical features, laboratory findings and outcome of patients with
      multiple myeloma presenting with extramedullary relapse.
AB  - Extramedullary plasmacytomas constitute a rare and not well studied subset of
      multiple myeloma (MM) relapses. We report the incidence, clinical-laboratory
      features and outcome of patients with MM and extramedullary relapse (ExMeR). A
      total of 303 patients with symptomatic MM were recorded in a 13-year period in
      two institutions. Twenty-eight cases of ExMeR (9%) were recorded. There was an
      increased frequency of elevated lactate dehydrogenase (LDH) (p = 0.026), bone
      plasmacytomas (p = 0.001) and fractures (p = 0.002) at diagnosis, in patients
      with ExMeR compared to the others. ExMeR was associated with an ominous outcome,
      high LDH, constitutional symptoms and a statistically significant decrease of
      monoclonal paraprotein compared to levels at diagnosis (p = 0.009). Prior
      treatment with bortezomib was associated with a decreased hazard of ExMeR (p =
      0.041). Overall survival (OS) was decreased in patients with ExMeR compared to
      the others (38 vs. 59 months, p = 0.006). Patients with MM with ExMeR have a
      lower OS and their clinical and laboratory features differ from those without.

PMID- 23151072
TI  - Ischemic tolerance induced by normobaric hyperoxia and evaluation of group I and
      II metabotropic glutamate receptors.
AB  - Preconditioning-induced ischemic tolerance is one of the most important
      mechanisms, responsible for the increased brain resistance after stroke. Recent
      studies over the past years have provided interesting insights into the molecular
      mechanisms of this neuroprotective phenomenon. In this research, we attempted to
      see changes in the expression of group I and II metabotropic glutamate receptors
      (mGluR I and II) following intermittent hyperoxia preconditioning. Rats were
      divided into five groups (hyperoxia-intact, hyperoxia-MCAO, room air-intact, room
      air- MCAO, room air-sham). Hyperoxia groups were exposed to 95% inspired O2 for 4
      h/day and 6 consecutive days. Oxygen level in room air groups was %21. 48 hours
      after pretreatment, MCAO-operated groups were subjected to focal cerebral
      ischemia for 60 min. 24 hours after reperfusion, neurologic deficit score (NDS)
      and brain infarct volume (IV) were evaluated in MCAO-operated subgroups. Sham
      operated and intact groups were used to assess expression of group I and II mGluR
      and glutathione (GSH) levels of core, penumbra and subcortex regions. The results
      of this study showed that preconditioning with intermittent HO decreased NDS and
      IV, increased GSH levels in subcortex, and upregulated mGluRs I and II
      significantly. Although additional studies will be required to further elucidate
      precise mechanism(s) of ischemic tolerance, it seems that intermittent HO may
      exert its protective effects in part through upregulation of mGluR I and II.

PMID- 23151073
TI  - Vascular factors and mitochondrial dysfunction: a central role in the
      pathogenesis of Alzheimer's disease.
AB  - The pathogenesis of Alzheimer's disease (AD) is complex, and only a minority of
      cases appears to be primarily genetic. A relationship between genetic and
      acquired vascular factors in AD has been hypothesized. Many vascular risk factors
      for AD, such as atherosclerosis, stroke and cardiac disease in the aging
      individual, could result in cerebrovascular dysfunction. A major vascular
      susceptibility factor gene is the apolipoprotein E gene, found to be associated
      with sporadic late-onset AD cases. Oxidative damage and mitochondrial dysfunction
      have been also implicated in the pathogenesis of AD, but the question as to
      whether they are involved in the onset and progression of the pathology or rather
      represent a consequence of neurodegeneration is still debated. Recent evidence
      suggests that chronic hypoperfusion may trigger mitochondrial dysfunction in
      vascular cells which, in turn, may enhance the production of reactive oxygen
      species. In this short review we revise the link between vascular factors and
      mitochondrial dysfunction in AD pathogenesis.

PMID- 23151074
TI  - Tissue plasminogen activator prevents restoration of tight junction proteins
      through upregulation of angiopoietin-2.
AB  - We examined the temporal profiles of changes in the expressions of tight junction
      proteins (TJPs; namely, claudin-5, occludin, and ZO-1) after focal cerebral
      ischemia/reperfusion in mice. We also examined the effects of delayed treatment
      with tissue plasminogen activator (tPA) on the expressions of TJPs and
      angiopoietin (Ang) -1/2/Tie2. Mice subjected to a 6-h filamental middle cerebral
      artery (MCA) occlusion were treated with tPA (10 mg/kg, intravenously, just after
      the start of reperfusion) or vehicle. The expressions of TJPs were significantly
      decreased in the early phase of ischemia/reperfusion, and then gradually
      recovered. A delayed treatment with tPA decreased the expressions of TJPs when
      examined at 42 h after reperfusion. In contrast, delayed tPA treatment markedly
      increased Ang-2, but not Ang-1 expression, when examined at 30 h after
      reperfusion. Treatment with tPA at 300 MUg/ml also significantly decreased Ang-
      2, but not Tie2 expression, in an in vitro monolayer model generated using human
      brain microvascular endothelial cells subjected to serum-deprivation. These
      findings suggest that delayed tPA treatment prevents recovery of TJPs following
      focal cerebral ischemia/reperfusion, partially via upregulation of Ang-2.

PMID- 23151075
TI  - Regional cerebral blood flow and cerebrovascular reactivity in Alzheimer's
      disease and vascular dementia assessed by arterial spinlabeling magnetic
      resonance imaging.
AB  - Hemodynamic disturbance in cerebral blood flow (CBF) is common in both
      Alzheimer's disease (AD) and vascular dementia (VaD).The aim of this study is to
      investigate the different patterns of regional cerebral blood flow (rCBF) change
      and cerebrovascular reactivity (CVR) in these two types of dementia. Mean flow
      velocity (MFV) of middle cerebral artery and rCBF were measured by Transcranial
      Doppler ultrasound (TCD) and arterial spin-labeling (ASL) magnetic resonance,
      separately. CVR was evaluated by MFV or rCBF change in response to 5% CO2
      inhalation. The ASL results showed that, rCBF was significantly lower in both the
      bilateral frontal and temporal lobes in AD group and lower in left frontal and
      temporal white matter in patients with VaD. CVR calculated by rCBF was impaired
      more severely in bilateral frontal cortices in AD. Conversely, TCD tests failed
      to demonstrate significant difference in MFV and CVR between the two groups. It
      is concluded that the different patterns detected by ASL in resting rCBF change
      and cerebrovascular reactivity in response to carbogen inhalation may serve as a
      potential marker to distinguish AD and VaD.

PMID- 23151076
TI  - Safety and efficacy of umbilical cord mesenchymal stem cell therapy in hereditary
      spinocerebellar ataxia.
AB  - Hereditary spinocerebellar ataxia (SCA) is a devastating, incurable disease. Stem
      cell-based therapies represent new promise for clinical research in neurology.
      The objectives of this study were to assess the feasibility, efficacy, and
      potential toxicity of human umbilical cord mesenchymal stem cells (UCMSCs)
      therapy in patients with SCA. Sixteen genomically diagnosed SCA patients were
      enrolled and received intravenous and intrathecal infusion of UCMSCs. Clinical,
      laboratory, and radiographic evaluations were conducted to assess the safety of
      UCMSC therapy. Efficacy was evaluated by the Berg Balance Scale (BBS) and
      International Cooperative Ataxia Rating Scale (ICARS) scores. Among the 16 cases,
      there were no serious transplant-related adverse events happened in 12 months
      follow-up. The majority of patients showed improved BBS and ICARS scores
      continuing for at least 6 months which indicated UCMSC therapy could alleviate
      SCA symptoms. This study suggested that UCMSC transplantation was safe and might
      delay the progression of SCA. This may represent a new therapeutic strategy for
      SCA and other genetic neurological diseases.

PMID- 23151078
TI  - CIAPIN1 siRNA inhibits proliferation, migration and promotes apoptosis of VSMCs
      by regulating Bcl-2 and Bax.
AB  - Migration, proliferation and apoptosis of vascular smooth muscle cells (VSMCs)
      have recently been identified as important processes in a variety of human
      vascular diseases, including atherosclerosis, arterial injury, and restenosis
      after angioplasty. These processes are regulated by interactions between the
      local cell-cell and cytokine environment. Cytokine induced apoptosis inhibitor
      (CIAPIN1) is a novel antiapoptotic molecule and plays a vitally important role in
      malignant phenotypes of cancers. However, the effect of CIAPIN1 on VSMCs has not
      been reported. In the present study, we constructed the adenovirus encoding
      CIAPIN1 siRNA and transduced it into VSMCs. The results demonstrated that CIAPIN1
      siRNA inhibited proliferation, migration and promotes apoptosis of VSMCs by
      regulating Bcl-2 and Bax. Our results suggest that CIAPIN1 siRNA might play the
      key role in VSMC biological function and provide the new therapeutic strategy for
      vascular diseases.

PMID- 23151079
TI  - Neuronal nitric oxide synthase and sympathetic nerve activity in neurovascular
      and metabolic systems.
AB  - Nitric oxide, derived from nitric oxide synthase (NOS), plays an important role
      in regulating sympathetic nerve activity. Neuronal NOS (nNOS) is expressed
      throughout the central and peripheral nervous system. nNOS has a
      sympathoinhibitory effect under physiological conditions by acting on different
      sites of the nervous system, including the paraventricular nucleus, the nucleus
      of the solitary tract, the rostral ventrolateral medulla, the carotid body and
      nerves in the kidney. nNOS is sympathoinhibitory in a range of diseases including
      chronic heart failure, chronic renal failure, hypertension and diabetes. nNOS is
      believed to mediate sympathoinhibitory effects induced by a range of signaling
      pathways including those promoted by angiotensin-converting enzyme 2 over
      expression; statin therapy; angiotensin II type 1 receptor blockers; exercise
      training; tumor necrosis factor-alpha blockade; superoxide dismutase mimetics;
      and estrogen replacement therapy. Increase in nNOS can increase
      sympathoinhibitory gamma-aminobutyric acid activity and decrease
      sympathoexcitatory angiotensin II signaling and glutamate activity. nNOS may have
      sympathoexcitatory effects in some circumstances such as chronic heart failure
      induced by prolonged high salt treatment. The effectiveness of nNOS upregulation
      in treating sympathetic overactive conditions including chronic heart failure
      needs to be further investigated.

PMID- 23151077
TI  - WISP1 neuroprotection requires FoxO3a post-translational modulation with
      autoregulatory control of SIRT1.
AB  - As a member of the secreted extracellular matrix associated proteins of the CCN
      family, Wnt1 inducible signaling pathway protein 1 (WISP1/CCN4) is garnering
      increased attention not only as a potent proliferative entity, but also as a
      robust cytoprotective agent during toxic insults. Here we demonstrate that WISP1
      prevents forkhead transcription factor FoxO3a mediated caspase 1 and caspase 3
      apoptotic cell death in primary neurons during oxidant stress. Phosphoinositide 3
      kinase (PI 3-K) and protein kinase B (Akt1) are necessary for WISP1 to foster
      posttranslational phosphorylation of FoxO3a and sequester FoxO3a in the cytoplasm
      of neurons with protein 14-3-3. Through an autoregulatory loop, WISP1 also
      minimizes deacytelation of FoxO3a, prevents caspase 1 and 3 activation, and
      promotes an effective neuroprotective level of SIRT1 activity through SIRT1
      nuclear trafficking and prevention of SIRT1 caspase degradation. Elucidation of
      the critical pathways of WISP1 that determine neuronal cell survival during
      oxidative stress may offer novel therapeutic avenues for neurodegenerative
      disorders.

PMID- 23151080
TI  - Membrane insertion of new AMPA receptors and LTP induced by glycine is prevented
      by blocking NR2A-containing NMDA receptors in the rat visual cortex in vitro.
AB  - N-methyl-D-aspartate receptors (NMDA-Rs) activation has been implicated in
      various forms of synaptic plasticity depending on the receptor subtypes involved.
      However, the contribution of NR2A and NR2B subunits in glycine-induced long-term
      potentiation (LTP) of miniature excitatory postsynaptic currents (mEPSCs) in
      layer II/III pyramidal neurons of the rat visual cortex remains unclear. The
      present study used whole-cell patch-clamp recordings in vitro to investigate the
      role of NR2A-containing and NR2B-containing NMDA-Rs in glycine-induced LTP in
      visual cortical slices from 13-15 day old rats. We found that glycine-induced LTP
      of mEPSCs was readily induced in layer II/III pyramidal neurons of the rat visual
      cortex with glycine. D-APV, a selective NMDA-R antagonist, blocked the
      glycineinduced LTP. Moreover, the selective NR2B-containing NMDA-R antagonists
      (Ro 25-6981) displayed no influence on the glycine-induced LTP. However, Zn2+, a
      voltage-independent NR2A-containing NMDA-R antagonist, prevented glycine-induced
      LTP. These results suggest that the glycine-induced LTP in layer II/III pyramidal
      neurons of the rat visual cortex is NMDA-R-dependent and requires NR2A-containing
      NMDA-Rs, not NR2B-containing NMDA-Rs.

PMID- 23151081
TI  - Unusual domain architecture of aminoacyl tRNA synthetases and their paralogs from
      Leishmania major.
AB  - BACKGROUND: Leishmania major, a protozoan parasite, is the causative agent of
      cutaneous leishmaniasis. Due to the development of resistance against the
      currently available anti-leishmanial drugs, there is a growing need for specific
      inhibitors and novel drug targets. In this regards, aminoacyl tRNA synthetases,
      the linchpins of protein synthesis, have received recent attention among the
      kinetoplastid research community. This is the first comprehensive survey of the
      aminoacyl tRNA synthetases, their paralogs and other associated proteins from L.
      major. RESULTS: A total of 26 aminoacyl tRNA synthetases were identified using
      various computational and bioinformatics tools. Phylogenetic analysis and domain
      architectures of the L. major aminoacyl tRNA synthetases suggest a probable
      archaeal/eukaryotic origin. Presence of additional domains or N- or C-terminal
      extensions in 11 aminoacyl tRNA synthetases from L. major suggests possibilities
      such as additional tRNA binding or oligomerization or editing activity. Five
      freestanding editing domains were identified in L. major. Domain assignment
      revealed a novel asparagine tRNA synthetase paralog, asparagine synthetase A
      which has been so far reported from prokaryotes and archaea. CONCLUSIONS: A
      comprehensive bioinformatic analysis revealed 26 aminoacyl tRNA synthetases and
      five freestanding editing domains in L. major. Identification of two EMAP
      (endothelial monocyte-activating polypeptide) II-like proteins similar to human
      EMAP II-like proteins suggests their participation in multisynthetase complex
      formation. While the phylogeny of tRNA synthetases suggests a probable
      archaeal/eukaryotic origin, phylogeny of asparagine synthetase A strongly
      suggests a bacterial origin. The unique features identified in this work provide
      rationale for designing inhibitors against parasite aminoacyl tRNA synthetases
      and their paralogs.

PMID- 23151084
TI  - Relations between molecular, crystalline, and lamellar structures of amylopectin.
AB  - Chain (branch) length distributions (CLD) from size-exclusion chromatography of a
      series of waxy starches were parametrized using both an empirical and a
      biosynthesis-based method and correlated with their crystalline-amorphous
      lamellar properties obtained from X-ray scattering. Correlations were best seen
      with the biosynthesis-based parametrization. This showed for the first time that
      the following links between the CLD and lamellar parameters, the average
      interlamellar repeat distance and the distribution of these distances, were
      decreased by an increase in the proportion of very short branches and were
      increased by an increase in the proportion of intermediate and longer chains;
      further, the shoulder and linear sections of the CLD were found to affect the
      lamellar repeat distance and distribution. These effects are rationalized in
      terms of branch-length effects on the production of crystallites and the presence
      of portions of longer branches in the amorphous regions.

PMID- 23151082
TI  - Applying a Health Network approach to translate evidence-informed policy into
      practice: a review and case study on musculoskeletal health.
AB  - BACKGROUND: While translation of evidence into health policy and practice is
      recognised as critical to optimising health system performance and health-related
      outcomes for consumers, mechanisms to effectively achieve these goals are neither
      well understood, nor widely communicated. Health Networks represent a framework
      which offers a possible solution to this dilemma, particularly in light of
      emerging evidence regarding the importance of establishing relationships between
      stakeholders and identifying clinical leaders to drive evidence integration and
      translation into policy. This is particularly important for service delivery
      related to chronic diseases. In Western Australia (WA), disease and population
      specific Health Networks are comprised of cross-discipline stakeholders who work
      collaboratively to develop evidence-informed policies and drive their
      implementation. Since establishment of the Health Networks in WA, over 50
      evidence-informed Models of Care (MoCs) have been produced across 18 condition or
      population-focused Networks. The aim of this paper is to provide an overview of
      the Health Network framework in facilitating the translation of evidence into
      policy and practice with a particular focus on musculoskeletal health. CASE
      PRESENTATION: A review of activities of the WA Musculoskeletal Health Network was
      undertaken, focussing on outcomes and the processes used to achieve them in the
      context of: development of policy, procurement of funding, stakeholder
      engagement, publications, and projects undertaken by the Network which aligned to
      implementation of MoCs.The Musculoskeletal Health Network has developed four MoCs
      which reflect Australian National Health Priority Areas. Establishment of
      community-based services for consumers with musculoskeletal health conditions is
      a key recommendation from these MoCs. Through mapping barriers and enablers to
      policy implementation, working groups, led by local clinical leaders and
      supported by the broader Network and government officers, have undertaken a range
      of integrated projects, such as the establishment of a community-based,
      multidisciplinary rheumatology service. The success of these projects has been
      contingent on developing relationships between key stakeholders across the health
      system. CONCLUSIONS: In WA, Networks have provided a sustainable mechanism to
      meaningfully engage consumers, carers, clinicians and other stakeholders;
      provided a forum to exchange ideas, information and evidence; and collaboratively
      plan and deliver evidence-based and contextually-appropriate health system
      improvements for consumers.

PMID- 23151083
TI  - Hashimoto's thyroiditis: celebrating the centennial through the lens of the Johns
      Hopkins hospital surgical pathology records.
AB  - Hashimoto's thyroiditis is now considered the most prevalent autoimmune disease,
      as well as the most common endocrine disorder. It was initially described in
      1912, but only rarely reported until the early 1950s. To celebrate this
      centennial, we reviewed the surgical pathology archives of the Johns Hopkins
      hospital for cases of Hashimoto's thyroiditis, spanning the period from May 1889
      to October 2012. Approximately 15,000 thyroidectomies were performed at this
      hospital over 124 years. The first surgical case was reported in 1942, 30 years
      after the original description. Then, 867 cases of Hashimoto's thyroiditis were
      seen from 1942 to 2012, representing 6% of all thyroidectomies. Hashimoto's
      thyroiditis was the sole pathological finding in 462 cases; it accompanied other
      thyroid pathologies in the remaining 405 cases. The most commonly associated
      pathology was papillary thyroid cancer, an association that increased
      significantly during the last two decades. The most common indication for
      thyroidectomy was a thyroid nodule that was cytologically suspicious for
      malignancy. Hashimoto's thyroiditis remains a widespread, intriguing, and
      multifaceted disease of unknown etiology one century after its description.
      Advances in the understanding of its pathogenesis and preoperative diagnosis will
      improve recognition and treatment of this disorder, and may one day lead to its
      prevention.

PMID- 23151085
TI  - Design, synthesis, and pharmacological evaluation of bis-2-(5-phenylacetamido
      1,2,4-thiadiazol-2-yl)ethyl sulfide 3 (BPTES) analogs as glutaminase inhibitors.
AB  - Bis-2-(5-phenylacetamido-1,2,4-thiadiazol-2-yl)ethyl sulfide (BPTES) is a potent
      and selective allosteric inhibitor of kidney-type glutaminase (GLS) that has
      served as a molecular probe to determine the therapeutic potential of GLS
      inhibition. In an attempt to identify more potent GLS inhibitors with improved
      drug-like molecular properties, a series of BPTES analogs were synthesized and
      evaluated. Our structure-activity relationship (SAR) studies revealed that some
      truncated analogs retained the potency of BPTES, presenting an opportunity to
      improve its aqueous solubility. One of the analogs, N-(5-{2-[2-(5-amino
      [1,3,4]thiadiazol-2-yl)-ethylsulfanyl]-ethyl}-[1,3,4]thiadiazol-2-yl)-2-phenyl
      acetamide 6, exhibited similar potency and better solubility relative to BPTES
      and attenuated the growth of P493 human lymphoma B cells in vitro as well as in a
      mouse xenograft model.

PMID- 23151086
TI  - Combination of recombinant factor VIIa and fibrinogen corrects clot formation in
      primary immune thrombocytopenia at very low platelet counts.
AB  - Haemostatic treatment modalities alternative to platelet transfusion are
      desirable to control serious acute bleeds in primary immune thrombocytopenia
      (ITP). This study challenged the hypothesis that recombinant activated factor VII
      (rFVIIa) combined with fibrinogen concentrate may correct whole blood (WB) clot
      formation in ITP. Blood from ITP patients (n = 12) was drawn into tubes
      containing 3.2% citrate and corn trypsin inhibitor 18.3 MUg/ml. WB [mean platelet
      count 22 * 10(9) /l (range 0-42)] was spiked in vitro with buffer, donor
      platelets (+40 * 10(9) /l), rFVIIa (1 or 4 MUg/ml), fibrinogen (1 or 3 mg/ml), or
      combinations of rFVIIa and fibrinogen. Coagulation profiles were recorded by
      tissue factor (0.03 pmol/l) activated thromboelastometry. Coagulation in ITP was
      characterized by a prolonged clotting time (CT, 1490 s (mean)) and a low maximum
      velocity (MaxVel, 3.4 mm * 100/s) and maximum clot firmness (MCF, 38.2 mm).
      Fibrinogen showed no haemostatic effect, whereas rFVIIa reduced the CT and
      increased the MaxVel. The combination of fibrinogen and rFVIIa revealed a
      significant synergistic effect, improving all parameters (CT 794 s, MaxVel 7.9 mm
      * 100/s, MCF 50.7 mm) even at very low platelet counts. These data suggest that
      rFVIIa combined with fibrinogen corrects the coagulopathy of ITP even at very low
      platelet counts, and may represent an alternative to platelet transfusion.

PMID- 23151087
TI  - Environmental justice implications of arsenic contamination in California's San
      Joaquin Valley: a cross-sectional, cluster-design examining exposure and
      compliance in community drinking water systems.
AB  - BACKGROUND: Few studies of environmental justice examine inequities in drinking
      water contamination. Those studies that have done so usually analyze either
      disparities in exposure/harm or inequitable implementation of environmental
      policies. The US EPA's 2001 Revised Arsenic Rule, which tightened the drinking
      water standard for arsenic from 50 MUg/L to 10 MUg/L, offers an opportunity to
      analyze both aspects of environmental justice. METHODS: We hypothesized that
      Community Water Systems (CWSs) serving a higher proportion of minority residents
      or residents of lower socioeconomic status (SES) have higher drinking water
      arsenic levels and higher odds of non-compliance with the revised standard. Using
      water quality sampling data for arsenic and maximum contaminant level (MCL)
      violation data for 464 CWSs actively operating from 2005-2007 in California's San
      Joaquin Valley we ran bivariate tests and linear regression models. RESULTS:
      Higher home ownership rate was associated with lower arsenic levels (beta
      coefficient= -0.27 MUg As/L, 95% (CI), -0.5, -0.05). This relationship was
      stronger in smaller systems (beta-coefficient = -0.43, CI, -0.84, -0.03). CWSs
      with higher rates of homeownership had lower odds of receiving an MCL violation
      (OR, 0.33; 95% CI, 0.16, 0.67); those serving higher percentages of minorities
      had higher odds (OR, 2.6; 95% CI, 1.2, 5.4) of an MCL violation. CONCLUSIONS: We
      found that higher arsenic levels and higher odds of receiving an MCL violation
      were most common in CWSs serving predominantly socio-economically disadvantaged
      communities. Our findings suggest that communities with greater proportions of
      low SES residents not only face disproportionate arsenic exposures, but unequal
      MCL compliance challenges.

PMID- 23151088
TI  - MicroRNA-100 is a potential molecular marker of non-small cell lung cancer and
      functions as a tumor suppressor by targeting polo-like kinase 1.
AB  - BACKGROUND: Polo-like kinase 1 (PLK1) is highly expressed in many human cancers
      and regulates critical steps in mitotic progression. Previously, we have reported
      that PLK1 was overexpressed in non-small cell lung cancer (NSCLC), but the
      underlying molecular mechanisms are not well understood. By using microRNA (miR)
      target prediction algorithms, we identified miR-100 that might potentially bind
      the 3'-untranslated region of PLK1 transcripts. The purpose of this study was to
      investigate the roles of miR-100 and its association with PLK1 in NSCLC
      development. METHODS: Taqman real-time quantitative RT-PCR assay was performed to
      detect miR-100 expression 10 NSCLC tissues and corresponding nontumor tissues.
      Additionally, the expression of miR-100 in 110 NSCLC tissues and its correlation
      with clinicopathological factors or prognosis of patients was analyzed. Finally,
      the effects of miR-100 expression on growth, apoptosis and cell cycle of NSCLC
      cells by posttranscriptionally regulating PLK1 expression were determined.
      RESULTS: MiR-100 was significantly downregulated in NSCLC tissues, and low miR
      100 expression was found to be closely correlated with higher clinical stage,
      advanced tumor classification and lymph node metastasis of patients. The overall
      survival of NSCLC patients with low miR-100 was significantly lower than that of
      those patients with high miR-100, and univariate and multivariate analyses
      indicated that low miR-100 expression might be a poor prognostic factor. Also,
      miR-100 mimics could lead to growth inhibition, G2/M cell cycle arrest and
      apoptosis enhancement in NSCLC cells. Meanwhile, miR-100 mimics could
      significantly inhibit PLK1 mRNA and protein expression and reduce the luciferase
      activity of a PLK1 3' untranslated region-based reporter construct in A549 cells.
      Furthermore, small interfering RNA (siRNA)-mediated PLK1 downregulation could
      mimic the effects of miR-100 mimics while PLK1 overexpression could partially
      rescue the phenotypical changes of NSCLC cells induced by miR-100 mimics.
      CONCLUSIONS: Our findings indicate that low miR-100 may be a poor prognostic
      factor for NSCLC patients and functions as a tumor suppressor by
      posttranscriptionally regulating PLK1 expression.

PMID- 23151089
TI  - The influence of music therapy on perceived stressors and anxiety levels of
      hemodialysis patients.
AB  - BACKGROUND: This study was designed as a pretest-posttest control group
      experiment. The aim was to identify the influence of music therapy on the
      perceived stressors and anxiety levels of hemodialysis (HD) patients. METHODS:
      The data were collected in HD Units of Ataturk University Yakutiye Research
      Hospital and Regional Education, Application and Research Hospital between
      February and March. The study population consisted of 104 patients who received
      dialysis. Since four patients refused to participate, the study was completed
      with 100 patients. While one-half of the patients formed a control group, the
      other half consisted of an experimental group. Patient introduction form,
      hemodialysis stressor scale, and state-trait anxiety inventory (STAI) forms were
      used to collect the data. HSS was used to identify the stressors perceived by the
      patients, and STAI form was used to classify anxiety levels. Data were analyzed
      by using t-test and chi-square test. RESULTS: It was found that differences
      between average pretest and posttest scores of perceived psychosocial,
      physiological, and total stressors were statistically significant. It was also
      found that differences between average pretherapy and posttherapy test scores of
      state and trait anxiety were statistically significant. CONCLUSIONS: Music
      therapy was influential in reducing anxiety levels and perceived stressors of HD
      patients. It is concluded that music therapy-as an independent nursing initiative
      can be used to help in fulfilling the physical, emotional, and psychological
      requirements of patients.

PMID- 23151090
TI  - A case of Mycobacterium goodii prosthetic valve endocarditis in a non
      immunocompromised patient: use of 16S rDNA analysis for rapid diagnosis.
AB  - BACKGROUND: Mycobacterium goodii is a rare cause of significant infection. M.
      goodii has mainly been associated with lymphadenitis, cellulitis, osteomyelitis,
      and wound infection. CASE PRESENTATION: A case of a 76-year-old Caucasian female
      is presented. The patient developed a prosthetic valve endocarditis caused by M.
      goodii. She had also suffered from severe neurological symptoms related to a
      septic emboli that could be demonstrated as an ischemic lesion found on CT of the
      brain. Transesophageal echocardiography verified a large vegetation attached to
      the prosthetic valve. Commonly used blood culture bottles showed growth of the
      bacteria after 3 days. CONCLUSIONS: Although M. goodii is rarely involved in
      these kinds of severe infections, rapidly growing mycobacteria should be
      recognized during conventional bacterial investigations and identified by
      molecular tools such as analysis of 16S rDNA. Species identification of
      nontuberculous mycobacteria is demanding and is preferably done in collaboration
      with a mycobacterial laboratory. An early diagnosis provides the opportunity for
      adequate treatment. In the present case, prolonged antimicrobial treatment and
      surgery with replacement of the prosthetic valve was successful.

PMID- 23151091
TI  - Preincubation in the Prothrombinase-induced Clotting Time test (PiCT) is
      necessary for in vitro evaluation of fondaparinux and to be avoided for the
      reversible, direct factor Xa inhibitor, rivaroxaban.
AB  - INTRODUCTION: There is no clear consensus about tests in vitro that are suitable
      for evaluating various factor Xa inhibitors. The availability of reversible and
      irreversible inhibitors further complicates the application of available assays.
      METHODS: We evaluated the suitability of the prothrombinase-induced clotting test
      (PiCT) for fondaparinux and rivaroxaban, as representatives for irreversible and
      reversible inhibition of factor Xa, with specific attention to preincubation
      times prior to re-calcification, in the context of automate program limitations.
      RESULTS: We demonstrate that the PiCT assay requires a preincubation step to
      allow inhibitory activity by fondaparinux. Without this step, inhibition in the
      test is minimal and lacking sufficient dynamic range. In contrast, to measure the
      reversible inhibition by rivaroxaban, we found any preincubation introduced an
      artifact in inhibition as exemplified by a biphasic pattern and only the test
      without a preincubation phase gave informative results. CONCLUSION: It is
      concluded that PiCT in its format with two steps is suitable for fondaparinux
      evaluation, while its format without preincubation (the one-addition format) is
      suitable for reversible inhibitors such as rivaroxaban. Unfortunately, both types
      of inhibitors cannot be compared in vitro in a single assay format.

PMID- 23151093
TI  - Ultrasound-triggered BSA/SPION hybrid nanoclusters for liver-specific magnetic
      resonance imaging.
AB  - Nanoclusters of superparamagnetic iron oxide nanoparticles (SPION) are developed
      for liver-specific magnetic resonance imaging (MRI) by a unique synthesis route.
      The process is efficient, environmentally benign, and straight forward within
      five minutes. The clustering effect is triggered in the presence of bovine serum
      albumin (BSA) aqueous phase under ultrasonication condition. The hydrophobic
      SPION are densely self-assembled into BSA/SPION hybrid nanoclusters with a
      uniform size of ~86 nm. The as-prepared BSA/SPION hybrid nanoclusters are found
      to be biocompatible and stable. They exhibit high transverse relaxivity and
      longitudinal relaxivity in water (r(2) and r(1) values are 600.8 and 4.3 s(-1)
      per mM of Fe(3+), respectively). In vivo T(2)-weighted MRI shows excellent
      enhancement in liver with an imaging time-window up to 48 h. In vivo
      biodistribution study indicates a gradual excretion of the nanoclusters via
      hepatobiliary (HB) processing. No toxicity is observed in the in vivo and ex vivo
      experiments. The BSA/SPION hybrid nanoclusters present great potential in MRI as
      the liver-specific contrast agents (CAs).

PMID- 23151092
TI  - Catalysis kinetics and porous analysis of rolling activated carbon-PTFE air
      cathode in microbial fuel cells.
AB  - The microbial fuel cell (MFC), being an environment-friendly technology for
      wastewater treatment, is limited by low efficiency and high cost. Power output
      based on capital cost had been greatly increased in our previous work by
      introducing a novel activated carbon (AC) air-cathode (ACAC). The catalysis
      behavior of this ACAC was studied here based on catalysis kinetics and pore
      analysis of both carbon powders and catalyst layers (CLs). Plain AC (AC1#),
      ultracapacitor AC (AC2#), and non-AC (XC-72) powders were used as catalysts. The
      electron transfer number (n) of oxygen reduction reaction (ORR) with CLs
      increased by 5-23% compared to those n values of corresponding carbon powders
      before being rolled to CLs with PTFE, while the n value of Pt/C decreased by 38%
      when it was brushed with Nafion as the CL, indicating that rolling procedure with
      PTFE binder substantially increased the catalytic activity of carbon catalysts.
      Two-four times larger in micropore area of AC powders than non-AC powder resulted
      in 1.3-1.9 times increase in power density of MFCs. In addition, more uniform
      distribution of microporosity was found in AC1# than in AC2#, which could be the
      reason for the 25% increase in power density of ACAC1# (1355 +/- 26 mW.m(-2))
      compared to 1086 +/- 8 mW.m(-2) of ACAC2#.

PMID- 23151094
TI  - Anti-inflammatory action of Tamarind seeds reduces hyperglycemic excursion by
      repressing pancreatic beta-cell damage and normalizing SREBP-1c concentration.
AB  - CONTEXT: Tamarindus indica L. (Leguminosae) is widely used as a traditional
      medicine for the management of diabetes mellitus (DM) in India, in addition to
      its anti-inflammatory activity. The present study has been designed to understand
      the correlation involved between antidiabetic and anti-inflammatory action of
      aqueous seed extract of T. indica (TSE) in diabetic rats. OBJECTIVE: In view of
      the fact that fatty acid synthesis and insulin release from islets of pancreas
      are regulated by sterol regulatory element-binding proteins (SREBP-1c) and
      cytosolic calcium, respectively, the objectives of present study were to
      determine the influence of TSE on SREBP-1c mRNA and to investigate the
      intracellular islets calcium [Ca2+](I) involvement and beta-cell mass
      preservation in insulin secretagogue action of TSE. MATERIALS AND METHODS: The
      effect of 4 weeks oral treatment (120 and 240 mg/kg) of high-performance liquid
      chromatography (HPLC) standardized TSE was studied in streptozotocin (STZ)
      induced diabetic male Wistar rats. Reverse transcription-PCR (RT-PCR) and a
      spectrofluorometer were used for mRNA concentration and islets [Ca2+](I)
      determination, respectively. The TUNEL assay was followed to study the pancreatic
      apoptosis. RESULTS: TSE (120 and 240 mg/kg) showed positive correlation with
      [Ca2+](I) and insulin release. The anti-inflammatory action of TSE was
      significant on nitric oxide (NO) and tumor necrosis factor-alpha (TNF-alpha) in
      addition to a favorable effect on beta-cell neogenesis and improved mRNA
      concentration of SREBP-1c. DISCUSSION AND CONCLUSION: The results suggest that
      anti-inflammatory action of Tamarind seeds on beta-cell cells of islets and
      cytokines contribute toward its antidiabetic activity by way of complex
      mechanisms of [Ca2+](I) handling and through SREBP-1c gene in liver.

PMID- 23151095
TI  - Halocycloalkenones as Diels-Alder dienophiles. Applications to generating useful
      structural patterns.
AB  - Halocycloalkenones are demonstrated to function as potent dienophiles in inter-
      and intramolecular Diels-Alder cycloadditions. We have found 2-brominated
      cycloalkenone dienophiles to be both highly endo selective and significantly more
      reactive than their nonhalogenated parent compounds. A method for the facile
      conversion of brominated cyclobutanone DA adducts to synthetically useful
      cyclopropyl functional handles is described.

PMID- 23151096
TI  - Atomic mobility in a polymer glass after shear and thermal cycles.
AB  - Molecular dynamics simulations and energy landscape analyses are carried out to
      study the atomic mobility of a polymer glass during the physical aging process
      that follows shear and thermal cycles. The mobility is characterized by the
      fraction of atoms moving more than their diameter in a given time interval. The
      mobility is enhanced after a shear or thermal cycle, and this enhancement decays
      with time. These mobility results are related to the position of the system on
      the energy landscape, as characterized by the average energy of the energy minima
      visited by the system; the mobility over longer time scales increases with the
      average energy of the energy minima visited, but the mobility over shorter time
      scales does not show a correlation with this average energy. From these results,
      we conclude that barriers separating metabasins composed of proximate energy
      minima, rather than barriers between individual energy minima, control the
      physical aging process. We also show that, after some finite time, the mobility
      following shear and thermal cycle appears to behave similarly to the mobility
      without perturbations; however, the system is at different regions of the energy
      landscape in these two cases, which implies that mobility alone does not
      characterize the state of the system.

PMID- 23151097
TI  - Spirituality: the Holy Grail of contemporary nursing practice.

PMID- 23151098
TI  - Spiritual care in nursing: an overview of published international research.
AB  - AIMS: This paper provides an overview of 80 papers on research into spiritual
      care in nursing between 2006 and 2010, to enable nurses and nurse managers to
      make use of evidence available to them to improve quality of care and implement
      best practice. BACKGROUND: Research into spiritual care has grown rapidly since a
      review of the field in 2006. EVALUATION: The CINAHL database was used to search
      for 'spirituality' OR 'spiritual care' AND 'nursing, looking for original
      research papers involving health-care practitioners. KEY ISSUES: Research is
      discussed in the following themes: nursing education; care of health-care
      practitioners, including nurses; descriptive and correlational research;
      assessment tools used in research; palliative care and oncology; culture and
      spiritual care research. Future research should take into account the risks of
      research that does not involve patients and the need for research that is
      translatable into contexts other than the setting under study. IMPLICATIONS FOR
      NURSING MANAGEMENT: Spiritual care research has implications for staff training
      and education, staff motivation and health, organisational culture, best
      practice, quality of care and, most importantly, for the health of patients.
      Nurse managers, and indeed all involved in management of nursing, should use this
      growing body of evidence to inform their spiritual care training, planning and
      delivery.

PMID- 23151099
TI  - An integrative review of spiritual assessment: implications for nursing
      management.
AB  - AIMS: To describe the current 'state of the art' in relation to spiritual
      assessment, focusing on quantitative, qualitative and generic approaches; to
      explore the professional implications of spiritual assessment; and to make
      practical recommendations to managers seeking to promote spiritual assessment in
      their places of work. METHOD: The paper integrates aspects of a recent systematic
      review of quantitative approaches to measuring spirituality and a recent meta
      synthesis of qualitative research into client perspectives of spiritual needs in
      health and the principles of generic assessment, before drawing on the wider
      literature to discuss a number of professional implications and making
      recommendations to nurse managers. IMPLICATIONS FOR NURSING MANAGEMENT: The
      issues to emerge from this paper are (1) that spiritual assessment is an
      increasingly important issue for nursing practice, (2) that the range of reliable
      and valid quantitative instruments for use in clinical practice is limited, (3)
      that there is overlap in the domains and categories of spirituality identified by
      quantitative and qualitative researchers, and (4) that nurse managers seeking to
      introduce spiritual assessment will do so in the context of a professional debate
      about the relevance of spirituality to contemporary practice.

PMID- 23151100
TI  - Who can give 'spiritual care'? The management of spiritually sensitive
      interactions between nurses and patients.
AB  - AIMS: This article considers the purpose of contemporary 'spiritual care' in
      order to help managers make informed decisions about its appropriate delivery in
      a clinical context. BACKGROUND: Although there are national policies in place
      concerning spiritual care, surveys indicate that nurses are reluctant to engage
      with the spiritual needs of patients. EVALUATION: A consideration of the
      character of spiritual care indicates the need to take account of the context of
      contemporary Western society. A model drawn from the social psychology of
      religion is used to analyse the different types of nurse-patient interaction
      available in the provision of spiritual care. KEY ISSUES: Although religious and
      spiritual commitments can vary widely, they are subject to the same pressures in
      a secular and pluralist social context. This enables some general guidelines to
      be developed. CONCLUSIONS: Effective spiritual care requires a consideration of
      both the patient's and the nurse's implicit and explicit religious commitments.
      IMPLICATIONS FOR NURSING MANAGEMENT: Nurse managers need to take account of the
      personal commitments of nurses when directing them to offer spiritual care. This
      article offers a diagnostic tool for deploying nurses in an appropriate way.

PMID- 23151101
TI  - Spirituality and spiritual care from a Careful Nursing perspective.
AB  - AIM: To provide a brief historical background of spirituality in nursing and
      describe spiritual care from the perspective of the Careful Nursing philosophy
      and professional practice model. BACKGROUND: The previously overshadowed role of
      spirituality in modern nursing has re-emerged and been widely debated. Less
      attention has been given to how spiritual care is implemented in practice.
      EVALUATION: Findings from historical research. Elaboration of a previously
      derived Careful Nursing concept and dimensions as a model of spiritual nursing
      practice values. KEY ISSUES: In spite of the diversity of nurses' philosophical
      beliefs about spirituality, common ground can be found when these are translated
      into spiritual nursing practice values. Spiritual care in nursing is primarily
      expressed in the attitudes and actions of nursing practice guided by spiritual
      nursing values, particularly recognition of human dignity, kindness, compassion,
      calmness, tenderness, and nurses' caring for themselves and one another.
      CONCLUSIONS: Spirituality is timelessly interwoven with nursing and health.
      Careful Nursing suggests a spiritual values model that could be useful in
      assisting nurses to reach a shared understanding of spirituality and a spiritual
      approach to nursing practice. IMPLICATIONS FOR NURSING MANAGEMENT: Spiritual
      nursing values can be shared and developed in practical ways so that they become
      truly integrated into everyday nursing practice.

PMID- 23151102
TI  - Creating conditions for good nursing by attending to the spiritual.
AB  - AIM: To note similarities, differences, and gaps in the literature on good
      nursing and spiritual care. BACKGROUND: Good nursing care is essential for
      meeting patient health needs. With growing recognition of the role of
      spirituality in health, understanding spiritual care as it relates to good
      nursing is important, especially as spiritual care has been recognized as the
      most neglected area of nursing care. METHODS: Nursing research, reports and
      discussion articles from a variety of countries were reviewed on the topics of
      good nursing, spiritual care and spirituality. KEY ISSUES: A nurse's spirituality
      and the nurse-patient relationship are integral to spiritual care and good
      nursing. CONCLUSIONS: There are many commonalities between good nursing and
      spiritual care. Personal attributes of the nurse are described in similar terms
      in research on spiritual care and good nursing. Professional attributes common to
      good nursing and spiritual care are the nurse-patient relationship, assessment
      skills and communication skills. IMPLICATIONS FOR NURSING MANAGEMENT: Good
      nursing through spiritual care is facilitated by personal spirituality, training
      in spiritual care and a culture that implements changes supportive of spiritual
      care. Further research is needed to address limitations in the scope of
      literature.

PMID- 23151103
TI  - Perspectives of spiritual care for nurse managers.
AB  - AIM: The purpose of this article is to explore the current status, perspectives
      and attitudes of nurse managers, nurses and others toward spiritual care.
      BACKGROUND: The nursing profession has not defined what is expected of the nurses
      and some question the need for teaching it in nursing education. The leadership
      roles of chief executive officers, nursing leaders, chaplains and others are
      considered. Gallup polls indicate people consider religion very important in
      their lives, but studies show patients report receiving none or limited care.
      EVALUATION: While the spiritual dimension of holistic care is considered
      essential to healing, its practice has yet to be achieved. KEY ISSUES:
      Requirements and criteria are in place through accreditation agencies and
      professional codes identifying spiritual care as part of the role of nursing, but
      guidelines for implementing spiritual care are vague and broadly stated.
      CONCLUSIONS: If nurse managers implement agency-wide programmes of spiritual care
      then clear direction can be provided for the nursing staff. IMPLICATIONS FOR
      NURSING MANAGEMENT: An agency-wide programme of spiritual care practice for
      nurses needs to be developed not only to provide evidence for accreditation but
      also to provide guidelines for nursing staff.

PMID- 23151104
TI  - A health services framework of spiritual care.
AB  - AIMS: To introduce a health services framework of spiritual care that addresses
      the empirical and applied issues surrounding spirituality and nursing practice.
      BACKGROUND: Despite over 20 years of study, the concept of spirituality is still
      under development, which limits application to nursing practice. METHODS: Three
      studies using a health services framework are reviewed: (1) a survey study of
      dying patients and family that describes the providers, types and outcomes of
      spiritual care; (2) an exploratory study of the process of spiritual care; and
      (3) a multi-level study of the structure and outcomes of spiritual care in long
      term care facilities. RESULTS: Spiritual care recipients identify family or
      friends (41%), clergy (17%) and health care providers (29%) as spiritual care
      providers. The most frequently reported type of spiritual care was help in coping
      with illness (87%). Just over half (55%) were satisfied with the care that they
      received. The processes of spiritual care involved: (1) presence, (2) opening
      eyes, and; (3) co-creating, which was a mutual and fluid activity between
      patients, family members and care providers. In long term care facilities,
      decedents who received spiritual care were perceived as receiving better overall
      care in the last month of life, when compared with those decedents who did not
      receive spiritual care. CONCLUSIONS: A health services framework provides a
      holistic view of spiritual care, one that is consistent with integrated nursing
      models. IMPLICATIONS FOR NURSING MANAGEMENT: By focusing on the structure,
      process and outcome elements of spiritual care within organisational settings,
      nursing management can develop feasible approaches to implement, improve and
      evaluate the delivery of this unique type of care.

PMID- 23151105
TI  - Discourses of spirituality and leadership in nursing: a mixed methods analysis.
AB  - AIM: To explore nursing discourses of spirituality and leadership. BACKGROUND:
      Global migration has brought unprecedented plurality to modern societies, and
      spirituality and religion into the purview of nurse leaders. METHOD: An
      innovative mixed methods approach, including a literature review, qualitative
      research and philosophic analysis, was utilized to examine discourses of
      spirituality in contexts of nursing leadership. After a literature synthesis
      protocol, 38 nursing literature sources were reviewed. Two qualitative studies
      examining plurality in hospital and home health settings provided data from 13
      nurse leaders. Philosophic inquiry added further depth and uncovered important
      underlying assumptions. RESULTS: Integrated analysis revealed a heterogeneous
      discourse in the nursing literature. Nurse leaders in the qualitative study
      evidenced awareness of the influence of spirituality and concern for inclusive
      health services, yet were cautious in integrating spirituality into leadership
      practices because of organisational and social influences. Assumptions regarding
      the role of leaders' spiritual values and the integration of spirituality into
      the workplace were revealed. CONCLUSION: Spirituality in nursing leadership is a
      relatively understudied field that is influenced by many contextual factors.
      IMPLICATIONS FOR NURSING MANAGEMENT: Scholarly engagement and research are needed
      to analyse the grounds for and appropriate approaches to the integration of
      spirituality in nursing leadership. Nurse managers are positioned to facilitate
      this process in their organisations.

PMID- 23151106
TI  - The impact of workplace spirituality dimensions on organisational citizenship
      behaviour among nurses with the mediating effect of affective organisational
      commitment.
AB  - AIM: To investigate the relationship between workplace spirituality dimensions
      and organisational citizenship behaviour (OCB) among nurses through the mediating
      effect of affective organisational commitment. BACKGROUND: Nurses' OCB has been
      considered recently to improve the quality of services to patients and
      subsequently, their performance. As an influential attitude, affective
      organisational commitment has been recognized to influence OCB, and ultimately,
      organisational performance. Meanwhile, workplace spirituality is introduced as a
      new organisational behaviour concept to increase affective commitment influencing
      employees' OCB. METHODS: The cross-sectional study and the respective data were
      collected with a questionnaire-based survey. The questionnaires were distributed
      to 305 nurses employed in four public and general Iranian hospitals. To analyse
      the data, descriptive statistics, Pearson coefficient, simple regression,
      multiple regression and path analyses were also conducted. RESULTS: The results
      indicated that workplace spirituality dimensions including meaningful work, a
      sense of community and an alignment with organisational values have a significant
      positive relationship with OCB. Moreover, affective organisational commitment
      mediated the impact of workplace spirituality on OCB. CONCLUSION: The concept of
      workplace spirituality through its dimensions predicts nurses' OCB, and affective
      organisational commitment partially mediated the relationship between workplace
      spirituality and OCB. IMPLICATIONS FOR NURSING MANAGEMENT: Nurses' managers
      should consider the potentially positive influence of workplace spirituality on
      OCB and affective commitment among their nurses. With any plan to increase
      workplace spirituality, the respective managers can improve nurses' performance
      and would be of considerable importance in the healthcare system.

PMID- 23151107
TI  - How undergraduate nursing students learn to care for patients spiritually in
      clinical studies--a review of literature.
AB  - AIM: To gain knowledge about what is known about how undergraduate nursing
      students learn to care for patients spiritually in their clinical studies.
      BACKGROUND: Spirituality is related to meaning, hope and comfort and spiritual
      care is part of nurses' responsibility. Clinical studies are vital for students
      to integrate knowledge, clinical reasoning and formation. However, nurses are
      important in role modelling. METHOD: A literature search was undertaken using
      international databases from 1980 to 2012. Articles were thoroughly evaluated and
      10 papers reviewed for this article. RESULTS: Four main areas emerged as
      essential for learning spiritual care in clinical studies: (1) the importance of
      learning in real-life situations with repeated exposure to patients in diverse
      placements; (2) use of pedagogical methods that assist students to understand,
      work with and reflect on patients' spirituality; (3) to be aware of and overcome
      conditions prohibiting spiritual care learning; and (4) to see spiritual care
      learning in connection with how students are prepared and how they are followed
      up after clinical studies. CONCLUSION: Clinical studies are fundamental to
      students' learning of spiritual care in nursing. IMPLICATIONS FOR NURSING
      MANAGEMENT: Nurse leaders play a key role in keeping holistic care a nursing
      focus and creating a good learning environment.

PMID- 23151109
TI  - Spiritual leadership and spiritual care in neonatology.
AB  - AIM: This article aims to explore spiritual care in the neonatal care environment
      in addition to highlighting the importance of spiritual leadership of a health
      team in that context. BACKGROUND: Neonatal care is an ethically demanding and
      stressful area of practice. Babies and families require spiritual needs to be
      recognized in the context of holistic care. Literature around spiritual
      leadership is explored to nurture workplace spirituality. EVALUATION: Analysis of
      a range of sources provides a theoretical reflection on spiritual leadership and
      spiritual care in neonatal care settings. KEY ISSUES: The literature identifies
      that the carers should consider carefully on how care given may affect the infant
      and family. Themes relating to the baby's and family's spiritual needs and those
      of the staff in this area are identified. Spiritual leadership by the manager
      will provide support to the staff and help spiritual need to be met in this area
      of practice. CONCLUSION: Spiritual needs should be acknowledged within neonatal
      care whether these are of babies, families or the team itself. IMPLICATIONS FOR
      NURSING MANAGEMENT: Managers have responsibility to ensure that spiritual care is
      carried out for babies and their families and to care for the team as spiritual
      leaders.

PMID- 23151108
TI  - Health-related religious rituals of the Greek Orthodox Church: their uptake and
      meanings.
AB  - AIM: To examine the uptake of religious rituals of the Greek Orthodox Church by
      relatives of patients in critical condition in Greece and to explore their
      symbolic representations and spiritual meanings. BACKGROUND: Patients and their
      relatives want to be treated with respect and be supported for their beliefs,
      practices, customs and rituals. However nurses may not be ready to meet the
      spiritual needs of relatives of patients, while the health-related religious
      beliefs, practices and rituals of the Greek Orthodox Christian denomination have
      not been explored. METHOD: This study was part of a large study encompassing 19
      interviews with 25 informants, relatives of patients in intensive care units of
      three large hospitals in Athens, Greece, between 2000 and 2005. In this paper
      data were derived from personal accounts of religious rituals given by six
      participants. RESULTS: Relatives used a series of religious rituals, namely
      blessed oil and holy water, use of relics of saints, holy icons, offering names
      for pleas and pilgrimage. CONCLUSION: Through the rituals, relatives experience a
      sense of connectedness with the divine and use the sacred powers to promote
      healing of their patients. IMPLICATIONS FOR NURSING MANAGEMENT: Nurse managers
      should recognize, respect and facilitate the expression of spirituality through
      the practice of religious rituals by patients and their relatives.

PMID- 23151110
TI  - Screening for spiritual distress in the oncology inpatient: a quality improvement
      pilot project between nurses and chaplains.
AB  - AIMS: A quality improvement initiative of nursing/chaplain collaboration on the
      early identification and referral of oncology patients at risk of spiritual
      distress. BACKGROUND: Research shows that spiritual distress may compromise
      patient health outcomes. These patients are often under-identified, and
      chaplaincy staffing is not sufficient to assess every patient. The current
      nursing admission form with a question of 'Any spiritual practices that may
      affect your care?' is ineffective in screening for spiritual distress. METHOD(S):
      Ten nurses on the oncology unit were recruited and trained in a two-question
      screening tool to be utilized upon admission. RESULTS: Six nurses made referrals;
      a total of 14 patients. Four (28%) were at risk of spiritual distress and were
      assessed by the chaplains. CONCLUSIONS: Nurses are interested in the spiritual
      well-being of their patients and observe spiritual distress. They appreciate
      terminology/procedures by which they can assess more productively the spiritual
      needs of their patients and make appropriate chaplain referrals. IMPLICATIONS FOR
      NURSING MANAGEMENT: The use of a brief spiritual screening protocol can improve
      nursing referrals to chaplains. The better utilization of chaplains that this
      enables can improve patient trust and satisfaction with their overall care and
      potentially reduce the harmful effects of spiritual distress.

PMID- 23151111
TI  - Quadrivalent Ann Arbor strain live-attenuated influenza vaccine.
AB  - Influenza B is responsible for significant morbidity in children and adults
      worldwide. For more than 25 years, two antigenically distinct lineages of
      influenza B viruses, B/Yamagata and B/Victoria, have cocirculated globally.
      Current influenza vaccine formulations are trivalent and contain two influenza
      subtype A strains (A/H1N1 and A/H3N2) but only one B strain. In a half of recent
      influenza seasons, the predominant circulating influenza B lineage was different
      from that contained in trivalent influenza vaccines. A quadrivalent live
      attenuated influenza vaccine (Q/LAIV) that contains two B strains, one from each
      lineage, has been developed to help provide broad protection against influenza B.
      Q/LAIV was recently approved for use in the USA in eligible individuals 2-49
      years of age. This review summarizes clinical trial data in support of Q/LAIV.

PMID- 23151112
TI  - Regarding: comparison of medial-to-lateral versus traditional lateral-to-medial
      laparoscopic dissection sequences for resection of rectosigmoid cancers:
      randomized controlled clinical trial.

PMID- 23151113
TI  - Is it possible for "traditional" laparoscopic surgery to leave "invisible" scars?
AB  - BACKGROUND: Improved cosmesis is widely recognized as the main benefit of single
      port laparoscopy (SPL). Recently, some centers have started to perform SPL in
      infants and neonates. However, in our experience, the cosmetic result following
      traditional laparoscopic surgery in this age range is excellent. This study
      assessed infants' postoperative scars following traditional laparoscopic surgery.
      SUBJECTS AND METHODS: Ten successive patients who previously underwent
      transperitoneal dismembered pyeloplasty were invited to attend for photographs of
      their abdominal wounds. All patients had had a 5-mm infra-umbilical port and two
      3.5-mm ports (epigastrium and iliac fossa). Photographs were all taken in the
      hospital's medical photography studio by the same medical photographer. Life-size
      photographs were then shown to 10 junior doctors who were asked to identify any
      visible scars and rate the cosmetic result. RESULTS: Six patients with a median
      age at surgery of 8 months (range, 4-15 months) attended for photographs a median
      of 13 months postoperatively (range, 8-19 months). None of the junior doctors was
      able to identify all three scars on any photo. No individual scar was
      identifiable by all reviewers. No scars were identified in over half (31) of the
      total of 60 photograph reviews. Of 180 scar reviews, only 37 (21%) were
      identified. The umbilical scars were least noticeable (3/60), followed by iliac
      fossa scars (11/60) and epigastric scars (23/60). Where any scars were correctly
      identified, the cosmetic result was always rated good (44%) or excellent (56%).
      CONCLUSIONS: Traditional laparoscopic surgery in infants can have an excellent
      cosmetic result with "invisible" scars. The cosmetic benefit and thus the role of
      SPL in infants are therefore questionable.

PMID- 23151114
TI  - Laparoscopic choledocholithotomy with rigid nephroscope.
AB  - BACKGROUND: Apart from the required expertise, a major deterrent to laparoscopic
      common bile duct (CBD) lithotomy (LCDL) remains the relatively prohibitive cost
      of the flexible choledochoscope, and it also has a shortcoming of not being
      effective in removal of large impacted CBD stones. SUBJECTS AND METHODS: All
      patients presenting with CBD stones were treated, without exclusion, by
      laparoscopic cholecystectomy plus transdochal LCDL after relevant investigations.
      LCDL was performed using a rigid nephroscope. The CBD was closed either with
      running 3-0 polyglactin acid (Vicryl; Ethicon) sutures without a stent or around
      a T tube in a few patients. Perioperative parameters were recorded in all
      patients. RESULTS: Transdochal LCDL was performed on 172 consecutive patients.
      Five patients had a prior open cholecystectomy, 26 patients presented with acute
      cholecystitis, 5 patients presented with mild acute pancreatitis, and 12 patients
      presented after failed endoscopic retrograde cholangiopancreatography. Twenty
      eight (16.28%) patients had multiple stones, 2 had biliary sludge, and no stone
      was found in 3 patients. Stone size varied from 4 to 12 mm. The average operative
      time was 68 minutes (range, 45-127 minutes). Primary repair was performed with 3
      0 Vicryl continuous sutures, and the T tube was left in place in 13 (7.56%)
      patients. Conversion to an open procedure was required in 8 patients (4.65%).
      Postoperatively, mild acute pancreatitis occurred in 1 patient, and biliary
      peritonitis occurred in 5 patients. CONCLUSIONS: Rigid scope transdochal LCDL is
      feasible, probably easier, better for impacted large CBD stones, and definitely
      more affordable.

PMID- 23151115
TI  - Self-injury among early adolescents: identifying segments protected and at risk.
AB  - BACKGROUND: Self-injury has been described as a "silent school crisis,"
      reflecting insufficient knowledge, confusion, lack of effective interventions,
      and the tendency for adults and youth to shy away from dealing directly with the
      issue. This purpose of this study was to identify distinct subgroups of youth who
      may be at increased risk of or reduced risk of nonsuicidal self-injury (NSSI).
      METHODS: The middle-school Youth Risk Behavior Survey was administered in 8
      district public middle schools in a large, southeastern county in Florida. A
      final sample size of 1748, representing approximately 92% of participants who
      self-reported attendance at 1 of the 8 middle schools (N = 1907) and 74% of the
      2350 surveys originally distributed, was used in this study. Chi-squared
      automatic interaction detection (CHAID) was used to identify distinct segments at
      risk for or protected from NSSI. RESULTS: CHAID analyses suggested large groups
      of youth at risk for (and not at risk) having ever tried self-injury including
      suicidal tendencies, substance use, low belief in life possibilities, and
      exposure to peer self-injury. Protective factors identified included having low
      to zero levels of suicidal tendencies, high belief in life possibilities, lack of
      substance use, and not being a victim of bullying. CONCLUSION: Engaging
      adolescents in prevention programs at early stage can reduce the chances of
      suicidal behavior as well as physical injury. Schools should take the lead in
      advocating for the development of evidence-based interventions that are capable
      of addressing factors that contribute to self-injury at multiple levels of
      youth's environments.

PMID- 23151116
TI  - SNAP participation in preschool-aged children and prevalence of overweight and
      obesity.
AB  - BACKGROUND: An increased prevalence of overweight and obesity for adults on
      government-funded nutrition assistance, such as the Supplemental Nutrition
      Assistance Program (SNAP), has been observed; however, this association among
      preschool-aged children is not well understood. Longitudinal research designs
      tracking changes in body mass index-for-age (BMI) in children of low-income
      households may provide a clearer picture of the association between SNAP
      participation and overweight and obesity among this age group. To determine if
      there is a relationship between SNAP participation and overweight and obesity
      prevalence in low-income, preschool children, we conducted a cross-sectional
      analysis of children in a Head Start program, and a longitudinal analysis of
      those children who were enrolled for 2 years. METHODS: Height and weight data and
      SNAP participation of 386 students (207 male, 179 female, 4.2 +/- 0.5 years)
      enrolled in a Head Start program were analyzed; data for 2 years were available
      for 167 of the students. Height and weight measures were used to determine BMI
      percentile per Centers for Disease Control and Prevention guidelines. SNAP
      participation was obtained through a nutritional questionnaire given to parents
      at time of Head Start Program enrollment. RESULTS: No significant differences
      were found between SNAP and non-SNAP participants for BMI percentile in either
      the cross-sectional or longitudinal analysis. BMI percentile increased for both
      groups over time, but failed to reach significance (p = .13). CONCLUSION: Future
      studies are warranted with an inclusion of a larger and more geographically
      diverse sample to further determine the association between SNAP participation
      and overweight and obesity in preschool-aged children.

PMID- 23151117
TI  - Physical activity and BMI: evidence from the Panel Study of Income Dynamics Child
      Development Supplement.
AB  - BACKGROUND: This study assessed the association between amount of physical
      activity and body mass index (BMI) percentile among middle and high school
      children. Total daily physical activity needs to include both in and out of
      school physical activity. METHODS: A secondary data analysis was performed on
      1306 children drawn from the Panel Study of Income Dynamics Child Development
      Supplement (CDS III, 2007). The dependent variable in this study was BMI
      percentile, while the independent variable was physical activity. The multinomial
      logistic regression model was used to assess the associations between physical
      activity and BMI percentile controlling for age, gender, race/ethnicity, parental
      income, and neighborhood safety. RESULTS: Children who engaged in low daily
      physical activity levels had 1.8 times the odds of being obese versus normal
      weight than those who engaged in moderate levels [odds ratio (OR) = 1.80,
      confidence interval (CI) = 1.31, 2.48]. African-American children had 1.6 times
      the odds of being obese than normal weight (OR = 1.55, CI = 0.99, 2.43) and
      Hispanic children had approximately 1.8 times the odds of being obese than normal
      weight in comparison to non-Hispanic white children (OR = 1.79, CI = 1.00, 3.21).
      Females had about 1.5 times the odds of being overweight than normal weight than
      males (OR = 1.49, CI = 1.04, 2.13). CONCLUSIONS: This study suggests that the
      accumulation of 30 minutes or more of daily physical activity may be effective in
      decreasing obesity prevalence among middle and high school-aged children.

PMID- 23151118
TI  - A modified obesity proneness model predicts adolescent weight concerns and
      inability to self-regulate eating.
AB  - BACKGROUND: The prevalence of obesity among high school students has risen in
      recent decades. Many high school students report trying to lose weight and some
      engage in disordered eating to do so. The obesity proneness model suggests that
      parents may influence their offspring's development of disordered eating. This
      study examined the viability of a modified obesity proneness model in a high
      school population. METHODS: Cross-sectional survey data from a random cluster
      sample of 1533 students in grades 9-12 from a Florida school district were
      analyzed using structural equation modeling. Variables included adolescents'
      weight concerns; inability to self-regulate eating; and perceptions about
      maternal comments about adolescents' weight, restrictive feeding practices, and
      maternal weight-related concern and values. RESULTS: All the model's originally
      proposed relationships were statistically significant, for example perceived
      maternal weight comments were associated with adolescents' weight concerns (beta
      = 0.64; p < .0001), and perceived maternal restrictive feeding practices were
      associated with adolescents' inability to self-regulate eating (beta = 0.22; p <
      .001). CONCLUSION: Some points of intervention should be subjected to empirical
      study. These interventions should give mothers guidance about appropriate feeding
      practices and discourage mothers from making weight-related comments to their
      offspring. Together, as 1 component of a multilevel intervention, these behaviors
      may help prevent disordered eating and obesity.

PMID- 23151119
TI  - Promoting healthy lifestyle behaviors: the Heart Smart Discussion Activity.

PMID- 23151120
TI  - Bring food and culture to the classroom.

PMID- 23151122
TI  - Response to Condon et al. comments on "Cancer clusters in the USA: what do the
      last twenty years of state and federal investigations tell us?".

PMID- 23151123
TI  - Stereodivergence in amine-catalyzed regioselective [4 + 2] cycloadditions of beta
      substituted cyclic enones and polyconjugated malononitriles.
AB  - Switchable reaction patterns of beta-substituted cyclic enones via amine-based
      dienamine activation are reported. While gamma-regioselective vinylogous Michael
      addition was observed with alkylidenemalononitriles, a completely different [4 +
      2] cycloaddition was obtained with allylidene- or alkynylidenemalononitrile
      substrates, affording densely substituted bicyclo[2.2.2]octanes or analogous
      architectures with moderate to excellent diastereo- and enantioselectivity by the
      catalysis of primary amines from natural quinidine or quinine. Importantly, high
      diastereodivergence was achieved through unusual hydrogen-bonding interactions of
      multifunctional primary-amine catalytic systems. Endo cycloadducts were
      efficiently produced using a combination of 9-amino-9-deoxyepiquinidine and
      salicylic acid, while exo variants were obtained using 6'-hydroxy-9-amino-9
      deoxyepiquinidine. Moreover, we successfully isolated the Michael addition
      intermediates in some cases, indicating that the above [4 + 2] reaction via
      dienamine catalysis may proceed by a stepwise Michael-Michael cascade rather than
      by a concerted Diels-Alder cycloaddition pathway.

PMID- 23151124
TI  - Analysis of genetic ancestry in the admixed Brazilian population from Rio de
      Janeiro using 46 autosomal ancestry-informative indel markers.
AB  - The Brazilian population is highly heterogeneous as a result of five centuries of
      inter-ethnic mating between native Amerindians, European colonizers and Africans
      arrived during slavery. This study aimed to assess the proportions of inter
      ethnic admixture in the Brazilian population of Rio de Janeiro using autosomal
      Ancestry-Informative Markers (AIMs). The autosomal data were also compared to the
      results expected from uniparental genetic markers. A total of 413 individuals
      were genotyped for 46 AIM-Indels and ancestry estimates were then assessed using
      HGDP-CEPH samples as ancestral reference. Individuals from Rio de Janeiro
      presented highly diverse admixture patterns. The global admixture estimates
      showed a predominantly European ancestry, above 55%, followed by African and
      Amerindian contributions. A separate self-declared Afro-descendant group also
      included in this study revealed an increased African ancestry, from ~30% to ~50%.
      The inter-ethnic admixture landscape of Rio de Janeiro captured by autosomal AIM
      Indels is in agreement with historical records and similar to that expected from
      uniparental mtDNA and Y-chromosome information. The AIM-Indel panel proved to be
      a rapid strategy to estimate autosomal genetic ancestry at individual and
      population levels in Rio de Janeiro, which is useful in population genetics and
      in case-control association studies.

PMID- 23151125
TI  - Youth report of healthcare transition counseling and autonomy support from their
      rheumatologist.
AB  - BACKGROUND: To increase understanding of the healthcare transition (HCT) process
      for young people living with Juvenile Idopathic Arthritis (JIA) by examining: 1)
      the extent to which youth report discussing HCT topics with their rheumatologist
      and 2) the association between youth perceptions of autonomy support from their
      rheumatologist and HCT discussions. METHODS: Data are from an online survey of
      youth in the United States with rheumatologic conditions (n= 134). HCT discussion
      was measured by 4 questions from the National Survey of Children with Special
      Health Care Needs. Youth perception of autonomy support was measured using a
      validated 6-item scale. RESULTS: One third of the youth (33.7%) reported talking
      to their rheumatologist about transferring to adult medicine. Less than half
      (40.8%) of respondents talked with their rheumatologist about adult healthcare
      needs, and less than a quarter (22.0%) discussed acquiring health insurance as an
      adult. Nearly two-thirds of respondents (62.7%) reported that their
      rheumatologist usually/always encourages self-care responsibility. Multivariate
      analyses revealed significant associations between rheumatologist support for
      youth autonomy and HCT counseling. CONCLUSION: The low frequency of HCT
      counseling reported indicates a continuing need to increase awareness among
      rheumatologist in the USA. The strong associations between rheumatologist's
      support for youth autonomy and HCT counseling suggest that developmentally "in
      tune" providers may deliver the best guidance about transition planning for youth
      living with arthritis.

PMID- 23151126
TI  - A qualitative study evaluating experiences of a lifestyle intervention in men
      with prostate cancer undergoing androgen suppression therapy.
AB  - BACKGROUND: The severe iatrogenic hypogonadal state induced by medical castration
      used for treatment of prostate cancer is associated with adverse effects
      including fatigue, increased fracture risk, and a decrease in skeletal muscle
      function, which negatively impact quality of life. We have previously reported
      beneficial changes in healthy lifestyle behaviors, physical function and fatigue
      as a result of a novel combined exercise and dietary advice intervention (a
      lifestyle intervention) in men with prostate cancer on androgen suppression
      therapy (AST). The aim of this research was to conduct a qualitative evaluation
      of the lifestyle intervention in these men with advanced prostate cancer
      receiving androgen suppression therapy (AST). METHODS: Twelve men with prostate
      cancer on AST took part in three focus groups in a UK higher education
      institution following the 12 week intervention. Sessions lasted between 45 and 60
      minutes in duration. All discussions were audio-taped and transcribed. A
      framework analysis approach was applied to the focus group data. An initial
      coding framework was developed from a priori issues listed in the topic guide and
      extended and refined following initial familiarization with the focus group
      transcripts. Line by line indexing of the transcripts was undertaken iteratively
      to allow for the incorporation of new codes. Coded sections of text were grouped
      together (charted) into themes and subthemes prior to a further process of
      comparison and interpretation. RESULTS: None of the participants involved in the
      trial were provided with information on how lifestyle changes might be beneficial
      to men with prostate cancer during the course of their standard medical
      treatment. We present novel findings that this intervention was considered
      beneficial for reducing anxiety around treatment and fear of disease progression.
      Men were supportive of the benefits of the intervention over conventional cancer
      survival discussion group arrangements as it facilitated peer support in addition
      to physical rehabilitation. CONCLUSIONS: The benefits of lifestyle changes in men
      with prostate cancer are not well appreciated by care providers despite a range
      of benefits becoming apparent. Strategies to implement exercise and dietary
      interventions in standard care should be further evaluated. TRIAL REGISTRATION:
      Current Controlled Trials ISRCTN88605738.

PMID- 23151127
TI  - Irradiation of cellulosic pulps: understanding its impact on cellulose oxidation.
AB  - Different pulp samples were irradiated by three energy sources: plasma, electron
      beaming, and gamma radiation. The effect of increased exposure to irradiation was
      studied by multidetector gel permeation chromatography with fluorescence labeling
      of carbonyl groups to quantify changes of the cellulose. Whereas plasma treatment
      had no effect, for gamma and electron beam the degradation primarily affects the
      high molar mass area. Kinetic calculations based on DPw were performed. They show
      close-to-linear relations with slopes in the same order of magnitude, suggesting
      that wood-derived pulps degrade slower than pulps from annual plants. The rise in
      carbonyl group content is linear with increasing dose. In particular, in pulps
      from annual plants, most detected carbonyl structures originate from the new
      reducing end groups. Therefore, oxidative modification of cellulose molecules by
      means of radiation appears to be viable for pulps produced from wood. Here the
      increase in oxidized functionalities is partially disconnected from chain
      scission.

PMID- 23151128
TI  - Novel type of linear mitochondrial genomes with dual flip-flop inversion system
      in apicomplexan parasites, Babesia microti and Babesia rodhaini.
AB  - BACKGROUND: Mitochondrial (mt) genomes vary considerably in size, structure and
      gene content. The mt genomes of the phylum Apicomplexa, which includes important
      human pathogens such as the malaria parasite Plasmodium, also show marked
      diversity of structure. Plasmodium has a concatenated linear mt genome of the
      smallest size (6-kb); Babesia and Theileria have a linear monomeric mt genome
      (6.5-kb to 8.2-kb) with terminal inverted repeats; Eimeria, which is distantly
      related to Plasmodium and Babesia/Theileria, possesses a mt genome (6.2-kb) with
      a concatemeric form similar to that of Plasmodium; Cryptosporidium, the earliest
      branching lineage within the phylum Apicomplexa, has no mt genome. We are
      interested in the evolutionary origin of linear mt genomes of Babesia/Theileria,
      and have investigated mt genome structures in members of archaeopiroplasmid, a
      lineage branched off earlier from Babesia/Theileria. RESULTS: The complete mt
      genomes of archaeopiroplasmid parasites, Babesia microti and Babesia rodhaini,
      were sequenced. The mt genomes of B. microti (11.1-kb) and B. rodhaini (6.9-kb)
      possess two pairs of unique inverted repeats, IR-A and IR-B. Flip-flop inversions
      between two IR-As and between two IR-Bs appear to generate four distinct genome
      structures that are present at an equi-molar ratio. An individual parasite
      contained multiple mt genome structures, with 20 copies and 2 - 3 copies per
      haploid nuclear genome in B. microti and B. rodhaini, respectively. CONCLUSION:
      We found a novel linear monomeric mt genome structure of B. microti and B.
      rhodhaini equipped with dual flip-flop inversion system, by which four distinct
      genome structures are readily generated. To our knowledge, this study is the
      first to report the presence of two pairs of distinct IR sequences within a
      monomeric linear mt genome. The present finding provides insight into further
      understanding of evolution of mt genome structure.

PMID- 23151131
TI  - Emerging role of the ubiquitin-proteasome system as drug targets.
AB  - The ubiquitin-proteosome system (UPS) regulates a wide range of cellular
      processes including protein degradation, DNA repair, transcription regulation,
      and cell signaling. Alterations and mutations in UPS components give rise to
      various human diseases, most prominently cancer and neurodegenerative disorders.
      Here, we review recent advances in UPS-based drug discovery highlighting the
      emerging relationships between the UPS and disease and discuss potential future
      therapeutic interventions. In particular, we focus on recent structural
      approaches in UPS and explain how the knowledge of protein structural details can
      guide the design of specifically targeted inhibitors.

PMID- 23151132
TI  - Comprehensive profiling of protein ubiquitination for drug discovery.
AB  - Alterations of the ubiquitin proteasome system (UPS) contribute to the
      progression of many diseases, such as cancer, neurodegenerative diseases,
      immunological disorders, and inflammation. Pharmacologic inhibition of specific
      ubiquitin regulatory enzymes and ubiquitination events is an important challenge
      in drug discovery. Identifying the substrates of the various enzymes that
      participate in the UPS is needed to determine which enzymes are potential drug
      candidates. Additionally, identifying the ubiquitination events regulated by
      pharmacological drugs can potentially discover new applications. In this review
      we describe mass spectrometry-based proteomic approaches for the identification
      of ubiquitinated proteins and their modification sites on a proteome-wide scale,
      focusing on the ubiquitin remnant profiling, a newly developed ubiquitination
      profiling technique. We then discuss the application of this approach for the
      profiling of ubiquitination events regulated by cell signaling pathways and
      explore its future applications for drug discovery in the UPS.

PMID- 23151133
TI  - Proteasome inhibition in transplantation-focusing on the experience with
      bortezomib.
AB  - The proteasome inhibition has been proved to be effective in the treatment of
      multiple myeloma and other malignancies. In addition to direct antitumor effects,
      proteasome inhibition also exerts strong effects on immune cells, such as T
      cells, B cells and DCs. Therefore, proteasome inhibition, through the utilization
      of small molecule drugs like bortezomib, could be used therapeutically to
      modulate immune responses in transplantation. In the current review, we discuss
      the emerging data, both preclinical and clinical, of using proteasome inhibition
      in treating complications of transplantation, such as antibody-mediated organ
      rejection (AMR) and graft-versus-host disease (GVHD). The therapy based on
      proteasome inhibition may present substantial opportunities as new therapeutic
      paradigms in transplantation.

PMID- 23151130
TI  - Deubiquitinating enzymes as promising drug targets for infectious diseases.
AB  - Deubiquitinating enzymes (DUBs) remove ubiquitin and ubiquitin-like modifications
      from proteins and they have been known to contribute to processes relevant in
      microbial infection, such as immune responses pathways. Numerous viral and
      bacterial DUBs have been identified, and activities of several host DUBs are
      known to be modulated during the infection process, either by a pathogen or by a
      host. Recently there have been attempts to take advantage of this feature and
      design therapeutic inhibitors of DUBs that can be used to limit the spread of
      infection. This review is focused on exploring the potential of DUBs in the
      treatment of infectious diseases.

PMID- 23151134
TI  - Dissecting bortezomib: development, application, adverse effects and future
      direction.
AB  - Bortezomib is the first-in-class proteasome inhibitor which has been used
      worldwide for the treatment of multiple myeloma and mantle cell lymphoma.
      Bortezomib is under evaluation as a single agent or in combination with other
      drugs for solid cancers and stem cell transplantation in clinical settings.
      However, adverse effects and drug resistance have been observed in patients,
      which is now emerging as a great challenge for the extended application of
      bortezomib. In this review, we will comprehensively discuss the development of
      bortezomib, the mechanism underlying its therapeutics, adverse effects and
      resistance. Second generation of bortezomib and its future directions will also
      be discussed.

PMID- 23151135
TI  - Targeting the ubiquitin E1 as a novel anti-cancer strategy.
AB  - The proteasomal pathway of protein degradation involves two discrete steps:
      ubiquitination and degradation. Blocking protein degradation by inhibiting the
      proteasome has well described biologic effects and proteasome inhibitors are
      approved for the treatment of multiple myeloma and mantle cell lymphoma. In
      contrast, the biological effects and potential therapeutic utility of inhibiting
      the ubiquitination cascade and the initiating enzyme UBA1 are less well
      understood. UBA1 is the initial enzyme in the ubiquitination cascade and
      initiates the transfer of ubiquitin molecules to target proteins where they are
      degraded by the proteasome. Here, we review the biological effects of UBA1
      inhibition and discuss UBA1 inhibitors as potential anti-cancer agents. Similar
      to proteasome inhibition, blocking UBA1 elicits an unfolded protein response and
      induces cell death in malignant cells over normal cells. Chemical UBA1 inhibitors
      have been developed that target different regions of the enzyme and inhibit its
      function through different mechanisms. These molecules are useful tools to
      understand the biology of UBA1 and highlight the potential of inhibiting this
      target for the treatment of malignancy.

PMID- 23151129
TI  - Targeting the ubiquitin-mediated proteasome degradation of p53 for cancer
      therapy.
AB  - Within the past decade, there has been a revolution in the types of drugs
      developed to treat cancer. Therapies that selectively target cancer-specific
      aberrations, such as kinase inhibitors, have made a dramatic impact on a subset
      of patients. In spite of these successes, there is still a dearth of treatment
      options for the vast majority of patients. Therefore, there is a need to design
      therapies with broader efficacy. The p53 tumor suppressor pathway is one of the
      most frequently altered in human cancers. However, about half of all cancers
      retain wild-type p53, yet through various mechanisms, the p53 pathway is
      otherwise inactivated. Targeting this pathway for reactivation truly represents
      the "holy grail" in cancer treatment. Most commonly, destabilization of p53 by
      various components of ubiquitin- proteasome system, notably the ubiquitin ligase
      MDM2 and its partner MDMX as well as various deubiquitinating enzymes (DUBs),
      render p53 inert and unresponsive to stress signals. Reinstating its function in
      cancer has been a long sought-after goal. Towards this end, a great deal of work
      has been devoted to the development of compounds that either interfere with the
      p53-MDM2 and p53- MDMX interactions, inhibit MDM2 E3 activity, or target
      individual DUBs. Here we review the current progress that has been made in the
      field, with a special emphasis on both MDM2 and DUB inhibitors. Developing
      inhibitors targeting the upstream of the p53 ubiquitination pathway will likely
      also be a valuable option.

PMID- 23151136
TI  - Regulation of skeletal muscle plasticity by glycogen synthase kinase-3beta: a
      potential target for the treatment of muscle wasting.
AB  - Muscle wasting is a prevalent and disabling condition in chronic disease and
      cancer and has been associated with increased mortality and impaired efficacy of
      surgical and medical interventions. Pharmacological therapies to combat muscle
      wasting are currently limited but considered as an important unmet medical need.
      Muscle wasting has been attributed to increased muscle proteolysis, and in
      particular ubiquitin 26S-proteasome system (UPS)-dependent protein breakdown.
      However, rates of muscle protein synthesis are also subject to extensive (patho)
      physiological regulation, and the balance between synthesis and degradation
      ultimately determines net muscle protein turnover. As multinucleated muscle
      fibers accommodate threshold changes in muscle protein content by the accretion
      and loss of muscle nuclei, myonuclear turnover may additionally determine muscle
      mass. Current insights in the mechanisms dictating muscle mass plasticity not
      only reveal intricate interactions and crosstalk between these processes, but
      imply the existence of signaling molecules that act as molecular switchboards,
      which coordinate and integrate cellular responses upon conditions that evoke
      changes in muscle mass. These "master regulators" of skeletal muscle mass
      plasticity are preferred targets for pharmacological modulation of skeletal
      muscle wasting. In this review Glycogen synthase kinase-3beta (GSK-3beta) is
      highlighted as a master regulator of muscle mass plasticity since, in addition to
      its role in UPS-mediated muscle protein degradation, it also controls protein
      synthesis, and influences myonuclear accretion and cell death. Moreover, the
      regulation of GSK-3beta activity as well as currently available pharmacological
      inhibitors are described and discussed in the context of multimodal treatment
      strategies aimed at the inhibition of GSK-3beta, and optimal exploitation of its
      potential role as a central regulator of skeletal muscle mass plasticity for the
      treatment of muscle wasting.

PMID- 23151138
TI  - The ubiquitin proteasome system as a potential target for the treatment of
      neurodegenerative diseases.
AB  - Neurodegenerative diseases are severe disorders characterized by progressive
      neurodegeneration in specific brain regions. The ubiquitin-proteasome system
      (UPS) is closely linked to neurodegenerative disease. In most cases, UPS
      impairment and dysregulation of the UPS components are frequently observed.
      Moreover, toxin-induced neurodegeneration produces neuronal cell death
      accompanied by decreased UPS function. These studies suggest an involvement of
      the UPS in these diseases. In this review, we summarize the changes to UPS
      components in neurodegenerative diseases and the association between the UPS and
      disease pathology. Dysfunction of the UPS results in the abnormal accumulation of
      proteins; thus, the UPS plays a critical role in disease pathogenesis. Drugs
      targeting specific components of the UPS may provide promising strategies for
      disease treatment.

PMID- 23151137
TI  - Cullin-RING Ligases as attractive anti-cancer targets.
AB  - The ubiquitin-proteasome system (UPS) promotes the timely degradation of short
      lived proteins with key regulatory roles in a vast array of biological processes,
      such as cell cycle progression, oncogenesis and genome integrity. Thus, abnormal
      regulation of UPS disrupts the protein homeostasis and causes many human
      diseases, particularly cancer. Indeed, the FDA approval of bortezomib, the first
      class of general proteasome inhibitor, for the treatment of multiple myeloma,
      demonstrated that the UPS can be an attractive anti-cancer target. However,
      normal cell toxicity associated with bortezomib, resulting from global inhibition
      of protein degradation, promotes the focus of drug discovery efforts on targeting
      enzymes upstream of the proteasome for better specificity. E3 ubiquitin ligases,
      particularly those known to be activated in human cancer, become an attractive
      choice. Cullin-RING Ligases (CRLs) with multiple components are the largest
      family of E3 ubiquitin ligases and are responsible for ubiquitination of ~20% of
      cellular proteins degraded through UPS. Activity of CRLs is dynamically regulated
      and requires the RING component and cullin neddylation. In this review, we will
      introduce the UPS and CRL E3s and discuss the biological processes regulated by
      each of eight CRLs through substrate degradation. We will further discuss how
      cullin neddylation controls CRL activity, and how CRLs are being validated as the
      attractive cancer targets by abrogating the RING component through genetic means
      and by inhibiting cullin neddylation via MLN4924, a small molecule indirect
      inhibitor of CRLs, currently in several Phase I clinical trials. Finally, we will
      discuss current efforts and future perspectives on the development of additional
      inhibitors of CRLs by targeting E2 and/or E3 of cullin neddylation and CRL
      mediated ubiquitination as potential anti-cancer agents.

PMID- 23151139
TI  - Cdc20: a potential novel therapeutic target for cancer treatment.
AB  - The Anaphase Promoting Complex (APC) has been characterized to play pivotal roles
      in regulating the timely cell cycle progression by forming two functionally
      distinct E3 ubiquitin ligase sub-complexes, APC(Cdc20) and APC(Cdh1).
      Interestingly, recent studies have shown that Cdh1 is functioning as a tumor
      suppressor whereas Cdc20 may function as an oncoprotein to promote the
      development and progression of human cancers. In this review, we will discuss the
      physiological role of Cdc20 and its downstream substrates in vitro and in the
      transgenic mouse model reminiscent of the pathogenesis of human cancers.
      Furthermore, we summarize recent findings to indicate that Cdc20 may represent a
      promising therapeutic target, thus development of Cdc20 inhibitors could be
      useful for achieving better treatment outcome of cancer patients.

PMID- 23151141
TI  - Pharmaceutical perspectives of HECT-type ubiquitin ligase Smurf1.
AB  - Smad ubiquitylation regulatory factor-1 (Smurf1) is a HECT-type ubiquitin ligase.
      The role of Smurf1 in cell development and migration, viral autophagy and immune
      responses has been the subject of intensive study in recent years. Smurf1
      regulates multiple biological networks, including TGF-beta and BMP signaling
      pathways, the non-canonical pathway and the Toll-like receptor pathway, and is
      linked to certain diseases and disorders, such as bone formation and embryonic
      development disorders. Increasing evidence suggests that Smurf1 could be a good
      candidate for further translational studies and a potential target for novel drug
      design. In this review, we summarize the physiological functions of Smurf1 and
      its associated disorders; and discuss the current state of drug discovery in the
      context of the ubiquitin-proteasomal system, and feasible pharmaceutical
      strategies toward Smurf1 and its regulators, as well as RNA interference and
      structure-based chemical drug selection.

PMID- 23151142
TI  - Targeting the ubiquitin-proteasome pathway--current perspectives and future
      directions.

PMID- 23151143
TI  - Effects of case management in community aged care on client and carer outcomes: a
      systematic review of randomized trials and comparative observational studies.
AB  - BACKGROUND: Case management has been applied in community aged care to meet frail
      older people's holistic needs and promote cost-effectiveness. This systematic
      review aims to evaluate the effects of case management in community aged care on
      client and carer outcomes. METHODS: We searched Web of Science, Scopus, Medline,
      CINAHL (EBSCO) and PsycINFO (CSA) from inception to 2011 July. Inclusion criteria
      were: no restriction on date, English language, community-dwelling older people
      and/or carers, case management in community aged care, published in refereed
      journals, randomized control trials (RCTs) or comparative observational studies,
      examining client or carer outcomes. Quality of studies was assessed by using such
      indicators as quality control, randomization, comparability, follow-up rate,
      dropout, blinding assessors, and intention-to-treat analysis. Two reviewers
      independently screened potentially relevant studies, extracted information and
      assessed study quality. A narrative summary of findings were presented. RESULTS:
      Ten RCTs and five comparative observational studies were identified. One RCT was
      rated high quality. Client outcomes included mortality (7 studies), physical or
      cognitive functioning (6 studies), medical conditions (2 studies), behavioral
      problems (2 studies) , unmet service needs (3 studies), psychological health or
      well-being (7 studies) , and satisfaction with care (4 studies), while carer
      outcomes included stress or burden (6 studies), satisfaction with care (2
      studies), psychological health or well-being (5 studies), and social consequences
      (such as social support and relationships with clients) (2 studies). Five of the
      seven studies reported that case management in community aged care interventions
      significantly improved psychological health or well-being in the intervention
      group, while all the three studies consistently reported fewer unmet service
      needs among the intervention participants. In contrast, available studies
      reported mixed results regarding client physical or cognitive functioning and
      carer stress or burden. There was also limited evidence indicating significant
      effects of the interventions on the other client and carer outcomes as described
      above. CONCLUSIONS: Available evidence showed that case management in community
      aged care can improve client psychological health or well-being and unmet service
      needs. Future studies should investigate what specific components of case
      management are crucial in improving clients and their carers' outcomes.

PMID- 23151140
TI  - When ubiquitin meets NF-kappaB: a trove for anti-cancer drug development.
AB  - During the last two decades, the studies on ubiquitination in regulating
      transcription factor NF-kappaB activation have elucidated the expanding role of
      ubiquitination in modulating cellular events by non-proteolytic mechanisms, as
      well as by proteasomal degradation. The significance of ubiquitination has also
      been recognized in regulating gene transcription, epigenetic modifications,
      kinase activation, DNA repair and subcellular translocation. This progress has
      been translated into novel strategies for developing anti-cancer therapeutics,
      exemplified by the success of the first FDA-approved proteasome inhibitor drug
      Bortezomib. Here we discuss the current understanding of the ubiquitin-proteasome
      system and how it is involved in regulating NF-kappaB signaling pathways in
      response to a variety of stimuli. We also focus on the recent progress of anti
      cancer drug development targeting various steps of ubiquitination process, and
      the potential of these drugs in cancer treatment as related to their impact on NF
      kappaB activation.

PMID- 23151144
TI  - Microwaves in the cold war: the Moscow embassy study and its interpretation.
      Review of a retrospective cohort study.
AB  - BACKGROUND: From 1953 to 1976, beams of microwaves of 2.5 to 4.0 GHz were aimed
      at the US embassy building in Moscow. An extensive study investigated the health
      of embassy staff and their families, comparing Moscow embassy staff with staff in
      other Eastern European US embassies. The resulting large report has never been
      published in peer reviewed literature. METHODS: The original report and other
      published comments or extracts from the report were reviewed. RESULTS: The
      extensive study reports on mortality and morbidity, recorded on medical records
      and by regular examinations, and on self-reported symptoms. Exposure levels were
      low, but similar or greater than present-day exposures to radiofrequencies
      sources such as cell phone base stations. The conclusions were that no adverse
      health effects of the radiation were shown. The study validity depends on the
      assumption that staff at the other embassies were not exposed to similar
      radiofrequencies. This has been questioned, and other interpretations of the data
      have been presented. CONCLUSIONS: The conclusions of the original report are
      supported. Contrary conclusions given in some other reports are due to
      misinterpretation of the results.

PMID- 23151145
TI  - Using longitudinal data from the Health Survey for England to resolve
      discrepancies in thresholds for haemoglobin in older adults.
AB  - Anaemia increases with age and is common among older people. Due to its
      relationship with morbidity and mortality, accurate diagnosis is important.
      Thresholds defining the diagnosis of anaemia have been the subject of
      considerable scientific debate, with both higher and lower cut-offs proposed.
      High haemoglobin is also a health risk in some but not all studies. Using
      nationally representative data of 5,329 adults aged 65 + years (Health Survey for
      England 1998, 2005, 2006), linked to administrative mortality data, this paper
      describes the relationship between haemoglobin levels and mortality, adjusted for
      age and other confounders. Among men, a reverse J shaped relationship was
      observed: relative to the modal group (140-149 g/l), those with 'mild anaemia' of
      120-129 g/l haemoglobin had a 56% (95% confidence interval 24-96%) greater
      mortality hazard, and those with 'severe anaemia', haemoglobin <120 g/l, had an
      87% (39-153%) greater hazard. At the other end of the range, those with
      haemoglobin >=160 g/l had 32% (2-70%) greater mortality hazard. Haemoglobin
      levels in women showed a similar but smaller, non-significant pattern: hazard
      ratio 1.32 (0.91-1.92) for severe anaemia (<110 g/l), and 1.30 (0.95-1.79) for
      high haemoglobin (>=150 g/l). This research supports the use of the World Health
      Organization thresholds (130 g/l for men, 120 g/l for women).

PMID- 23151146
TI  - Calciphylaxis: a report of six cases and review of literature.
AB  - Calciphylaxis is usually a fatal condition that develops in a few chronic renal
      failure patients, and it is characterized by calcifications in subcutaneous
      arteries, infarcts in skin, and the neighboring subcutis. Calciphylaxis, once
      considered as a rare condition, has been reported to have an annual incidence of
      1% and a prevalence of 4% in dialysis patients. We describe our clinical
      experience in six end-stage renal disease patients on dialysis that presented
      with calciphylaxis and died due to sepsis, and review the pathogenesis,
      epidemiology, clinical and histopathologic features, and treatment of
      calciphylaxis. Physicians should initially consider the possibility of
      calciphylaxis in case of development of skin lesions in chronic renal failure
      patients with impaired calcium, phosphorus, and parathyroid hormone levels. The
      most important cause of mortality in this condition is infection. Therefore,
      differential diagnosis of these lesions from systemic vasculitis in their early
      stages and withdrawal of immunosuppressive therapy that increases the tendency to
      infections are essential.

PMID- 23151148
TI  - Enhancing charge transfer kinetics by nanoscale catalytic cermet interlayer.
AB  - Enhancing the density of catalytic sites is crucial for improving the performance
      of energy conversion devices. This work demonstrates the kinetic role of 2 nm
      thin YSZ/Pt cermet layers on enhancing the oxygen reduction kinetics for low
      temperature solid oxide fuel cells. Cermet layers were deposited between the
      porous Pt cathode and the dense YSZ electrolyte wafer using atomic layer
      deposition (ALD). Not only the catalytic role of the cermet layer itself but the
      mixing effect in the cermet was explored. For cells with unmixed and fully mixed
      cermet interlayers, the maximum power density was enhanced by a factor of 1.5 and
      1.8 at 400  degrees C, and by 2.3 and 2.7 at 450  degrees C, respectively, when
      compared to control cells with no cermet interlayer. The observed enhancement in
      cell performance is believed to be due to the increased triple phase boundary
      (TPB) density in the cermet interlayer. We also believe that the sustained
      kinetics for the fully mixed cermet layer sample stems from better thermal
      stability of Pt islands separated by the ALD YSZ matrix, which helped to maintain
      the high-density TPBs even at elevated temperature.

PMID- 23151147
TI  - Serological identification of Tektin5 as a cancer/testis antigen and its
      immunogenicity.
AB  - BACKGROUND: Identification of new cancer antigens is necessary for the efficient
      diagnosis and immunotherapy. A variety of tumor antigens have been identified by
      several methodologies. Among those antigens, cancer/testis (CT) antigens have
      became promising targets. METHODS: The serological identification of antigens by
      the recombinant expression cloning (SEREX) methodology has been successfully used
      for the identification of cancer/testis (CT) antigens. We performed the SEREX
      analysis of colon cancer. RESULTS: We isolated a total of 60 positive cDNA clones
      comprising 38 different genes. They included 2 genes with testis-specific
      expression profiles in the UniGene database, such as TEKT5 and a CT-like gene, A
      kinase anchoring protein 3 (AKAP3). Quantitative real-time RT-PCR analysis showed
      that the expression of TEKT5 was restricted to the testis in normal adult
      tissues. In malignant tissues, TEKT5 was aberrantly expressed in a variety of
      cancers, including colon cancer. A serological survey of 101 cancer patients with
      different cancers by ELISA revealed antibodies to TEKT5 in 13 patients, including
      colon cancer. None of the 16 healthy donor serum samples were reactive in the
      same test. CONCLUSION: We identified candidate new CT antigen of colon cancer,
      TEKT5. The findings indicate that TEKT5 is immunogenic in humans, and suggest its
      potential use as diagnostic as well as an immunotherapeutic reagent for cancer
      patients.

PMID- 23151149
TI  - Designing an interprofessional training program for shared decision making.
AB  - For implementation of patient-centered treatment in interprofessional health care
      units, such as rehabilitation teams, external participation (interaction between
      patient and health care professionals) and internal participation (communication,
      coordination and cooperation in the interprofessional team) need to be
      considered. The aim of this study is to identify the preferences of patients and
      health care professionals concerning internal and external participation in
      rehabilitation clinics, in order to develop an interprofessional shared decision
      making (SDM) training program for health care professionals to enhance both types
      of participation. Therefore, a cross-sectional mixed-methods study was
      implemented in four rehabilitation clinics. The study consists of two parts:
      focus groups with patients and a survey of experts (senior health care
      professionals from medicine, psychotherapy, physical therapy and nursing). More
      time, more respect from the health care professionals and the desire for more
      participation in decision-making processes were mentioned most frequently by
      patients (n = 36) in the focus groups. The health care professionals (n = 32) saw
      most deficits in internal participation, e.g. management of feedback, talking
      with difficult team members and moderate conflict discussion. The results of both
      assessments have been used to develop an interprofessional SDM training program
      for implementing internal and external participation in interprofessional teams
      in medical rehabilitation.

PMID- 23151150
TI  - Visible light-driven alpha-Fe2O3 nanorod/graphene/BiV1-xMoxO4 core/shell
      heterojunction array for efficient photoelectrochemical water splitting.
AB  - We report the design, synthesis, and characterization of a novel heterojunction
      array of alpha-Fe(2)O(3)/graphene/BiV(1-x)Mo(x)O(4) core/shell nanorod for
      photoelectrochemical water splitting. The heterojunction array was prepared by
      hydrothermal deposition of alpha-Fe(2)O(3) nanorods onto Ti substrate, with
      subsequent coating of graphene interlayer and BiV(1-x)Mo(x)O(4) shell by
      photocatalytic reduction and a spin-coating approach, respectively. The
      heterojunction yielded a pronounced photocurrent density of ~1.97 mA/cm(2) at 1.0
      V vs Ag/AgCl and a high photoconversion efficiency of ~0.53% at -0.04 V vs
      Ag/AgCl under the irradiation of a Xe lamp. The improved photoelectrochemical
      properties benefited from (1) the enhanced light absorption due to behavior of
      the "window effect" between the alpha-Fe(2)O(3) cores and BiV(1-x)Mo(x)O(4)
      shells, and (2) the improved separation of photogenerated carriers at the alpha
      Fe(2)O(3) nanorod/graphene/BiV(1-x)Mo(x)O(4) interfaces. Our results demonstrate
      the advantages of the novel graphene-mediated core/shell heterojunction array and
      provide a valuable insight for the further development of such materials.

PMID- 23151151
TI  - Solvent effect on the potential energy surfaces for the one-electron reduction of
      CF3X (X = Cl, Br, I) molecules: a DFT PCM study.
AB  - In this article, an effect of solvent on potential energy surfaces, constructed
      at the PBE1PBE/aug-cc-pVTZ level vs C-X distances for the neutral molecules
      CF(3)X (X = Cl, Br, I) and the corresponding radical anions CF(3)X-, is studied
      using the polarizable continuum model (PCM). The properties and energy changes in
      these compounds in the presence of argon, acetonitrile (ACN), and dimethyl
      sulfoxide (DMSO) are compared to the results obtained earlier in vacuo. The
      presence of solvent very weakly influences the neutral molecules, but it
      significantly changes properties of radical anions, such as structural parameters
      and partial charges on atoms. The effect of solvent is manifested also in strong
      modification of the potential energy surfaces, on which the minima corresponding
      to the locally stabilized forms of CF(3)X- are shallower in argon, and in ACN and
      DMSO, they almost disappear. This in turn results in much higher energy barriers
      (by about 0.2-0.3 eV) for the reductive cleavage of C-X bonds in polar solvents
      than in vacuo. Despite different dielectric constants of ACN and DMSO, the
      potential energy surfaces obtained in these two solvents are very similar, and
      the activation energies equal, respectively, 0.635 and 0.637 eV for CF(3)Cl;
      0.479 and 0.481 eV for CF(3)Br; and 0.336 and 0.337 eV for CF(3)I.

PMID- 23151152
TI  - Decolonization of patients and health care workers to control nosocomial spread
      of methicillin-resistant Staphylococcus aureus: a simulation study.
AB  - BACKGROUND: Control of methicillin-resistant Staphylococcus aureus (MRSA)
      transmission has been unsuccessful in many hospitals. Recommended control
      measures include isolation of colonized patients, rather than decolonization of
      carriage among patients and/or health care workers. Yet, the potential effects of
      such measures are poorly understood. METHODS: We use a stochastic simulation
      model in which health care workers can transmit MRSA through short-lived hand
      contamination, or through persistent colonization. Hand hygiene interrupts the
      first mode, decolonization strategies the latter. We quantified the effectiveness
      of decolonization of patients and health care workers, relative to patient
      isolation in settings where MRSA carriage is endemic (rather than sporadic
      outbreaks in non-endemic settings caused by health care workers). RESULTS:
      Patient decolonization is the most effective intervention and outperforms patient
      isolation, even with low decolonization efficacy and when decolonization is not
      achieved immediately. The potential role of persistently colonized health care
      workers in MRSA transmission depends on the proportion of persistently colonized
      health care workers and the likelihood per colonized health care worker to
      transmit. As stand-alone intervention, universal screening and decolonization of
      persistently colonized health care workers is generally the least effective
      intervention, especially in high endemicity settings. When added to patient
      isolation, such a strategy would have maximum benefits if few health care workers
      cause a large proportion of the acquisitions. CONCLUSIONS: In high-endemicity
      settings regular screening of health care workers followed by decolonization of
      MRSA-carriers is unlikely to reduce nosocomial spread of MRSA unless there are
      few persistently colonized health care workers who are responsible for a large
      fraction of the MRSA acquisitions by patients. In contrast, decolonization of
      patients can be very effective.

PMID- 23151153
TI  - Cardiac rhabdomyomas associated with tuberous sclerosis complex in 11 children:
      presentation to outcome.
AB  - Cardiac rhabdomyomas (CRs) are the most common heart tumors in children and
      closely associated with tuberous sclerosis complex (TSC). This study was
      performed to assess the presentation type, clinical course, treatment modalities,
      and outcome of the patients with rhabdomyoma, associated with TSC. We reviewed
      our patients with cardiac rhabdomyomas (CRs), who had received a diagnosis of TSC
      previously or during the follow-up period between June 1996 and January 2012,
      retrospectively. Thirty-two patients with TSC were evaluated and among them 11
      patients (34%) were associated with CRs. Five patients (45%) had multiple tumors
      and consequently a total of 29 CRs were analyzed in our study. The median follow
      up period was 2 years (range: 1 week-15 years). Clinical presentation was cardiac
      murmur in three patients, cyanosis in two patients and arrhythmia in one patient.
      Five patients were asymptomatic at the diagnosis and CRs were detected during
      routine cardiac evaluation for TSC. Cardiac tumors were diagnosed prenatally in
      two patients. Spontaneous regression rate was 31% and we experienced a complete
      regression of a tumor with an echogenic bordered tissue defect and septal
      thinning in a patient. Three patients had hemodynamically significant tumor
      obstruction; two of them underwent surgery. The other patient, who had multiple
      CRs, was treated medically with everolimus because of high-risk potential of
      surgery. Although surgical resection is the preferred treatment in most of the
      patients with hemodynamic instability, we need novel alternative medical
      therapies in some critically ill patients who cannot be operated due to various
      reasons.

PMID- 23151154
TI  - Clustering of time-course gene expression profiles using normal mixture models
      with autoregressive random effects.
AB  - BACKGROUND: Time-course gene expression data such as yeast cell cycle data may be
      periodically expressed. To cluster such data, currently used Fourier series
      approximations of periodic gene expressions have been found not to be
      sufficiently adequate to model the complexity of the time-course data, partly due
      to their ignoring the dependence between the expression measurements over time
      and the correlation among gene expression profiles. We further investigate the
      advantages and limitations of available models in the literature and propose a
      new mixture model with autoregressive random effects of the first order for the
      clustering of time-course gene-expression profiles. Some simulations and real
      examples are given to demonstrate the usefulness of the proposed models. RESULTS:
      We illustrate the applicability of our new model using synthetic and real time
      course datasets. We show that our model outperforms existing models to provide
      more reliable and robust clustering of time-course data. Our model provides
      superior results when genetic profiles are correlated. It also gives comparable
      results when the correlation between the gene profiles is weak. In the
      applications to real time-course data, relevant clusters of coregulated genes are
      obtained, which are supported by gene-function annotation databases. CONCLUSIONS:
      Our new model under our extension of the EMMIX-WIRE procedure is more reliable
      and robust for clustering time-course data because it adopts a random effects
      model that allows for the correlation among observations at different time
      points. It postulates gene-specific random effects with an autocorrelation
      variance structure that models coregulation within the clusters. The developed R
      package is flexible in its specification of the random effects through user-input
      parameters that enables improved modelling and consequent clustering of time
      course data.

PMID- 23151155
TI  - Controlling the particle size of ZrO2 nanoparticles in hydrothermally stable
      ZrO2/MWCNT composites.
AB  - The composite of multiwalled carbon nanotubes (MWCNTs) decorated with ZrO(2)
      nanoparticles, synthesized by a grafting method followed by high-temperature
      annealing, was studied. The oxygen functionalized MWCNT surface uniformly
      disperses and stabilizes the oxide nanoparticles to an extent that is controlled
      by the metal oxide loading and thermal annealing temperature. This ZrO(2)/MWCNT
      also withstands decomposition in a hydrothermal environment providing potential
      applications in the catalysis of biomass conversion (e.g., aqueous phase
      reforming). The ZrO(2)/MWCNT have been characterized by (scanning) transmission
      electron microscopy ((S)TEM), X-ray diffraction (XRD), in situ small-angle X-ray
      scattering (SAXS), in situ wide-angle X-ray scattering (WAXS), and near edge X
      ray fine structure (NEXAFS) for the purpose of a comprehensive analysis of the
      ZrO(2) particle size and particle size stability.

PMID- 23151156
TI  - Acupuncture, Counseling, and Usual care for Depression (ACUDep): study protocol
      for a randomized controlled trial.
AB  - BACKGROUND: The evidence on the effect of acupuncture or counseling for
      depression is not conclusive yet is sufficient to warrant further research. Our
      aim is to conduct a full-scale RCT to determine the clinical and cost
      effectiveness of acupuncture and counseling compared to usual care alone. We will
      explore the experiences and perspectives of patients and practitioners.
      METHODS/DESIGN: Randomized controlled trial with three parallel arms: acupuncture
      plus usual care, counseling plus usual care, and usual care alone, in conjunction
      with a nested qualitative study using in-depth interviews with purposive samples
      of trial participants. PARTICIPANTS: Patients aged over 18 years diagnosed with
      depression or mood disorder by their GP and with a score of 20 or above on the
      Beck Depression Inventory (BDI-II).Randomization: Computer randomization by York
      Trials Unit to acupuncture, counseling, and usual care alone in proportions of
      2:2:1, respectively, with secure allocation concealment. INTERVENTIONS: Patients
      allocated to acupuncture and counseling groups receive the offer of up to 12
      weekly sessions. Both interventions allow flexibility to address patient
      variation, yet are constrained within defined protocols. Acupuncture is based on
      traditional Chinese medicine and counseling is non-directive within the
      humanistic tradition. OUTCOME: The PHQ-9 is the primary outcome measure,
      collected at baseline, 3, 6, 9, and 12 months. Also measured is BDI-II, SF-36
      Bodily pain subscale, and EQ-5D. Texted mood scores are collected weekly over the
      first 15 weeks. Health-related resource use is collected over 12 months.
      ANALYSIS: The sample size target was for 640 participants, calculated for an
      effect size of 0.32 on the PHQ-9 when comparing acupuncture with counseling given
      90% power, 5% significance, and 20% loss to follow-up. ANALYSIS of covariance
      will be used on an intention-to-treat basis. Thematic analysis will be used for
      qualitative data. We will compare incremental cost-effectiveness of the three
      treatment options at 12 months. DISCUSSION: Ethical approval was obtained in
      October 2009. There were six subsequent protocol amendments, the last of which
      was approved in January 2012. Recruitment of 755 participants took place over 18
      months. Data collection will be completed by June 2012. No interim analyses have
      been conducted. TRIAL REGISTRATION: ISRCTN63787732.

PMID- 23151157
TI  - Microbial structures, functions, and metabolic pathways in wastewater treatment
      bioreactors revealed using high-throughput sequencing.
AB  - The objective of this study was to explore microbial community structures,
      functional profiles, and metabolic pathways in a lab-scale and a full-scale
      wastewater treatment bioreactors. In order to do this, over 12 gigabases of
      metagenomic sequence data and 600,000 paired-end sequences of bacterial 16S rRNA
      gene were generated with the Illumina HiSeq 2000 platform, using DNA extracted
      from activated sludge in the two bioreactors. Three kinds of sequences (16S rRNA
      gene amplicons, 16S rRNA gene sequences obtained from metagenomic sequencing, and
      predicted proteins) were used to conduct taxonomic assignments. Specially,
      relative abundances of ammonia-oxidizing archaea (AOA) and ammonia-oxidizing
      bacteria (AOB) were analyzed. Compared with quantitative real-time PCR (qPCR),
      metagenomic sequencing was demonstrated to be a better approach to quantify AOA
      and AOB in activated sludge samples. It was found that AOB were more abundant
      than AOA in both reactors. Furthermore, the analysis of the metabolic profiles
      indicated that the overall patterns of metabolic pathways in the two reactors
      were quite similar (73.3% of functions shared). However, for some pathways (such
      as carbohydrate metabolism and membrane transport), the two reactors differed in
      the number of pathway-specific genes.

PMID- 23151159
TI  - Using the internet to estimate influenza vaccine effectiveness.

PMID- 23151158
TI  - Norovirus vaccine development: next steps.

PMID- 23151160
TI  - Moving Helicobacter pylori vaccine development forward with bioinformatics and
      immunomics.

PMID- 23151161
TI  - Neutrophils found to boost antibody production; potential application for
      vaccines.

PMID- 23151162
TI  - CD8(+) T-cell-mediated immunity against malaria: a novel heterologous prime-boost
      strategy.
AB  - Recently, a vaccine against malaria was successfully tested in a human Phase III
      trial. The efficacy of this vaccine formulation, based on the Plasmodium
      falciparum circumsporozoite protein, was approximately 50% and correlated with
      the presence of antibodies specific to the infective stages of the malaria
      parasites. Different strategies are being pursued to improve vaccine efficacy
      levels. One such strategy is the induction of specific cytotoxic T cells that can
      destroy the intracellular hepatocyte stages of the malaria parasite. In this
      study, a novel vaccination protocol was developed to elicit strong immune
      responses mediated by CD8(+) cytotoxic cells specific to the circumsporozoite
      protein. As proof-of-concept, the authors used the rodent malaria Plasmodium
      yoelii parasite. The vaccination strategy consisted of a heterologous prime-boost
      vaccination regimen involving porcine parvovirus-like particles for priming and
      the modified vaccinia virus Ankara for the booster immunization, both of which
      expressed the immunodominant CD8 epitope of the P. yoelii circumsporozoite
      protein. Results from this experimental model were extremely meaningful. This
      vaccination strategy led to a significant T-cell immune response mediated by
      CD8(+) multifunctional T effector and effector-memory cells. However, most
      importantly for the malaria vaccine development was the fact that following a
      sporozoite challenge, immunized mice eliminated more than 97% of the malaria
      parasites during the hepatocyte stages. These results confirm and extend a vast
      body of knowledge showing that a heterologous prime-boost vaccination strategy
      can elicit strong CD8(+) T-cell-mediated protective immunity and may increase the
      efficacy of malaria vaccines.

PMID- 23151164
TI  - Towards the development of a fully protective Plasmodium falciparum antimalarial
      vaccine.
AB  - If ever there were a truism then it would be that a completely protective
      Plasmodium falciparum malaria vaccine is desperately needed. Our institute has
      devoted all its efforts during the last 30 years to developing a fully
      protective, minimal subunit-based, multiepitope, multistage (targeting sporozoite
      and merozoite proteins), chemically synthesized antimalarial vaccine, given that
      peptides with high binding activity to their corresponding host cells (liver
      cells or red blood cells) form the springboard for vaccine design. However, such
      conserved high activity binding peptides have to be specifically modified to
      render them into highly immunogenic and protection-inducing peptides since they
      are immunologically silent. These modifications, analyzed at the 3D structural
      level by (1)H-NMR, allow them a better fit into the MHC II-peptide-T-cell
      receptor complex to induce an appropriate immune response, providing a rational
      and logical approach (analyzed at the single atom level) for vaccine development,
      particularly in the field of malaria.

PMID- 23151165
TI  - Plasmodium falciparum malaria vaccines: current status, pitfalls and future
      directions.
AB  - Currently, a vaccine against malaria has not yet been licensed. Different
      approaches have been explored with different immune responses, but neither has
      fulfilled the criteria for being approved. The most advanced candidate, RTS,S, is
      undergoing Phase III studies and comprises virus-like particles, liposomes and
      immunostimulatory molecules. Other strategies are based on the use of polymeric
      particles, viral vectors or virosomes. Here, the authors have summarized the
      clinical advances that have been made in the field of Plasmodium falciparum to
      date, since it is the main causal agent of severe malaria. The best strategies to
      further develop a vaccine against malaria have also been discussed. In fact, an
      appropriate formulation should be immunogenic, safe and well tolerated, and as
      far as possible, avoid the use of needles and require a low number of
      immunizations. Moreover, issues such as storage, costs and so on, have to be
      taken into account.

PMID- 23151163
TI  - Accelerating the development of a therapeutic vaccine for human Chagas disease:
      rationale and prospects.
AB  - Chagas disease is a leading cause of heart disease affecting approximately 10
      million people in Latin America and elsewhere worldwide. The two major drugs
      available for the treatment of Chagas disease have limited efficacy in
      Trypanosoma cruzi-infected adults with indeterminate (patients who have
      seroconverted but do not yet show signs or symptoms) and determinate (patients
      who have both seroconverted and have clinical disease) status; they require
      prolonged treatment courses and are poorly tolerated and expensive. As an
      alternative to chemotherapy, an injectable therapeutic Chagas disease vaccine is
      under development to prevent or delay Chagasic cardiomyopathy in patients with
      indeterminate or determinate status. The bivalent vaccine will be comprised of
      two recombinant T. cruzi antigens, Tc24 and TSA-1, formulated on alum together
      with the Toll-like receptor 4 agonist, E6020. Proof-of-concept for the efficacy
      of these antigens was obtained in preclinical testing at the Autonomous
      University of Yucatan. Here the authors discuss the potential for a therapeutic
      Chagas vaccine as well as the progress made towards such a vaccine, and the
      authors articulate a roadmap for the development of the vaccine as planned by the
      nonprofit Sabin Vaccine Institute Product Development Partnership and Texas
      Children's Hospital Center for Vaccine Development in collaboration with an
      international consortium of academic and industrial partners in Mexico, Germany,
      Japan, and the USA.

PMID- 23151167
TI  - Vaccines and vaccination against tick-borne encephalitis.
AB  - Tick-borne encephalitis (TBE) is an emerging viral zoonosis and is endemic from
      Japan, China, Mongolia and Russia, to Central Europe and France. There is no
      specific treatment and TBE can be fatal. The four licensed prophylactic vaccines
      are produced according to WHO manufacturing requirements. Large clinical trials
      and postmarketing surveillance demonstrated safety and efficacy of the two
      European vaccines. The two Russian vaccines showed their effectiveness in daily
      use, but limited published data are available on controlled clinical trials.
      Vaccination recommendations in endemic areas vary significantly. In some
      countries, public vaccination programs are implemented. The WHO has recently
      issued recommendations on evidence-based use of TBE vaccines. However, more data
      are needed regarding safety, efficacy and long-term protection after vaccination.

PMID- 23151169
TI  - Optimizing efficacy of mucosal vaccines.
AB  - In general, there are only a few vaccines administered via mucosal routes, as the
      mucosal immune system presents numerous hurdles, including diversity in mucosal
      surface structure, complexity in immune cell interaction and limitations in
      experimental methodology. This therefore necessitates a range of strategies to be
      used for each target area. With reference to the three main routes of delivery
      and associated mucosal surfaces (oral/intestinal, nasal/respiratory and female
      genital tract), this review examines how coadministration of immune-stimulatory
      molecules, adjuvants, delivery systems and mucoadhesives are used to improve
      mucosal vaccine efficacy. Key considerations to the development of next
      generation mucosal vaccines include improved efficacy and safety, technological
      advancements in medical devices to enable convenience and better administration,
      as well as reduced manufacturing costs.

PMID- 23151168
TI  - Resurgence of pertussis calls for re-evaluation of pertussis animal models.
AB  - Pertussis has recently re-emerged in well-vaccinated populations most likely due
      to a combination of pathogen adaptation and waning of vaccine-induced pertussis
      immunity. Changes in genomic content of the etiologic agent, Bordetella
      pertussis, observed in the postvaccination era can have a bearing on the efficacy
      of vaccines currently in use. Moreover, protective immune responses in vaccinees
      wane gradually depending on their originally induced size and breadth, and memory
      responses may not be as regularly boosted by circulating strains as was the case
      in the prevaccination era. This pertussis scenario asks for new, improved
      vaccines with at least a longer duration of protection. Pertussis vaccine
      research, development and postmarketing surveillance require re-evaluation and
      innovation of the currently available pertussis animal models, with emphasis on
      the use of circulating B. pertussis strains.

PMID- 23151171
TI  - Single trial ERP reading based on parallel factor analysis.
AB  - The extraction of task-related single trial ERP features has recently gained much
      interest, in particular in simultaneous EEG-fMRI applications. In this study, a
      specific decomposition known as parallel factor analysis (PARAFAC) was used, in
      order to retrieve the task-related activity from the raw signals. Using visual
      detection task data, acquired in normal circumstances and simultaneously with
      fMRI, differences between distinct task-related conditions can be captured in the
      trial signatures of specific PARAFAC components when applied to ERP data arranged
      in Channels * Time * Trials arrays, but the signatures did not correlate with the
      fMRI data. Despite the need for parameter tuning and careful preprocessing, the
      approach is shown to be successful, especially when prior knowledge about the
      expected ERPs is incorporated.

PMID- 23151166
TI  - Chikungunya virus and prospects for a vaccine.
AB  - In 2004, chikungunya virus (CHIKV) re-emerged from East Africa to cause
      devastating epidemics of debilitating and often chronic arthralgia that have
      affected millions of people in the Indian Ocean Basin and Asia. More limited
      epidemics initiated by travelers subsequently occurred in Italy and France, as
      well as human cases exported to most regions of the world, including the Americas
      where CHIKV could become endemic. Because CHIKV circulates during epidemics in an
      urban mosquito-human cycle, control of transmission relies on mosquito abatement,
      which is rarely effective. Furthermore, there is no antiviral treatment for CHIKV
      infection and no licensed vaccine to prevent disease. Here, we discuss the
      challenges to the development of a safe, effective and affordable chikungunya
      vaccine and recent progress toward this goal.

PMID- 23151172
TI  - Nitric oxide as a mediator for defense responses.
AB  - Sequential recognition of invading microbes and rapid induction of plant immune
      responses comprise at least two recognition systems. Early basal defenses are
      initiated by pathogen-associated molecular patterns and pattern recognition
      receptors (PRR) in the plasma membrane. Pathogens produce effectors to suppress
      defense but plants, in turn, can sense such effectors by dominant plant
      resistance (R) gene products. Plant PRR and R proteins modulate signaling
      networks for defense responses that rely on rapid production of reactive nitrogen
      species (RNS) and reactive oxygen species (ROS). Recent research has shown that
      nitric oxide (NO) mainly mediates biological function through chemical reactions
      between locally controlled accumulation of RNS and proteins leading to potential
      alteration of protein function. Many proteins specifically regulated by NO and
      participating in signaling during plant defense response have been identified,
      highlighting the physiological relevance of these modifications in plant
      immunity. ROS function independently or in cooperation with NO during defense,
      modulating the RNS signaling functions through the entire process. This review
      provides an overview of current knowledge about regulatory mechanisms for NO
      burst and signaling, and crosstalk with ROS in response to pathogen attack.

PMID- 23151173
TI  - Framework and components for effective discharge planning system: a Delphi
      methodology.
AB  - BACKGROUND: To reduce avoidable hospital readmissions, effective discharge
      planning and appropriate post discharge support care are key requirements. This
      study is a 3-staged process to develop, pretest and pilot a framework for an
      effective discharge planning system in Hong Kong. This paper reports on the
      methodology of Delphi approach and findings of the second stage on pre-testing
      the framework developed so as to validate and attest to its applicability and
      practicability in which consensus was sought on the key components of discharge
      planning. METHODS: Delphi methodology was adopted to engage a group of
      experienced healthcare professionals to rate and discuss the framework and
      components of an effective discharge planning. The framework was consisted 36
      statements under 5 major themes: initial screening, discharge planning process,
      coordination of discharge, implementation of discharge, and post discharge follow
      up. Each statement was rated independently based on 3 aspects including clarity,
      validity and applicability on a 5-point Likert-scale. Statement with 75% or above
      of participants scoring 4-5 on all 3 aspects would be included in the discharge
      planning framework. For those statements not reaching 75% of consensus in any one
      of the aspect, it would be revised or discarded following the group discussion,
      and be re-rated in another round. RESULTS: A total of 24 participants
      participated in the consensus-building process. In round one rating, consensus
      was achieved in 25 out of 36 statements. Among those 11 statements not reaching
      consensus, the major concern was related to the "applicability" of the
      statements. The participants expressed a lack of manpower, skills and time in
      particular during weekends and long holidays in carrying out assessment and care
      plans within 24 h after admission. There were also timeliness and availability
      issue in providing transportation and necessary equipment to the patients. To
      make the statements more applicable, the wordings of some of the statements were
      revised to provide greater flexibility. Due to the lack of a statement in
      clarifying the role of the members of the healthcare professional team, one
      additional statement on the role and responsibility of the multidisciplinary team
      members was added. The first theme on "initial screening" was further revised to
      "initial screening and assessment" to better reflect the first stage of discharge
      planning process. After two rounds of rating process, all the 36 statements and
      the newly added statement reached consensus CONCLUSIONS: A structured, systematic
      and coordinated system of hospital discharge system is required to facilitate the
      discharge process to ensure a smooth patient transition from the hospital to the
      community and improve patient health outcome in both clinical and social aspect.
      The findings of this paper provide a reference framework helping policymakers and
      hospital managers to facilitate the development of a coherent and systematized
      discharge planning process. Adopting a Delphi approach also demonstrates the
      values of the method as a pre-test (before the clinical run) of the components
      and requirements of a discharge planning system taking into account of the local
      context and system constraints, which would lead to improvements to its
      applicability and practicability. To confirm the applicability and practicability
      of this consensus framework for discharge planning system, the third stage of
      process of development of the discharge planning framework is to apply and pilot
      the framework in a hospital setting to evaluate its feasibility, applicability
      and impact in hospital including satisfaction from both the perspectives of staff
      and patients.

PMID- 23151174
TI  - The effect of a year of highly active antiretroviral therapy on immune
      reconstruction and cytokines in HIV/AIDS patients.
AB  - To investigate the effect of a year of highly active antiretroviral therapy
      (HAART) on immune reconstruction and cytokine production in HIV/AIDS patients, 35
      AIDS patients were recruited for HAART treatment and 35 healthy volunteers were
      assigned as controls. The dynamic changes in HIV load, blood T cell subset
      counts, as well as interleukin (IL)-12, interferon (IFN)-gamma, and interferon
      inducible protein-10 (IP-10) levels in AIDS patients were evaluated before HAART
      and at 6 and 12 months after therapy. Our results revealed that HIV virus load in
      HIV/AIDS patients was reduced below the detectable limit after patients received
      6 months of HAART. CD3(+)CD4(+), CD4(+)CD45RA(+)62L(+), and CD4(+)CD45RO(+) T
      cells were found to be significantly decreased in HIV/AIDS patients compared to
      the healthy controls, but increased after HAART. CD3(+)CD8(+) and CD8(+)CD38(+)
      cells were found to be increased in HIV/AIDS patients but decreased after HAART.
      Plasma IL-12 and IFN-gamma levels were lower but IP-10 level was higher in AIDS
      patients compared to controls. HAART significantly improved IL-12 and IFN- gamma
      levels but reduced IP-10 level in AIDS patients (p<0.01). CD4(+)CD45RA(+)62L(+)
      and CD4(+)CD45RO(+) T cells were positively correlated with plasma IL-12/IFN
      gamma levels (p<0.05), but negatively correlated with plasma IP-10 level.
      However, CD3(+)CD8(+) cells were negatively correlated with plasma IL-12 and IFN
      gamma levels, but positively correlated with IP-10 level (p<0.05). HAART benefits
      HIV/AIDS patients by not only inhibiting virus replication but also by
      contributing to immune reconstruction, such as restoring subsets of T cells and
      adjusting cytokine production in HIV/AIDS patients.

PMID- 23151175
TI  - Tetrakis(hydroxymethyl) phosphonium chloride as a covalent cross-linking agent
      for cell encapsulation within protein-based hydrogels.
AB  - Native tissues provide cells with complex, three-dimensional (3D) environments
      comprised of hydrated networks of extracellular matrix proteins and sugars. By
      mimicking the dimensionality of native tissue while deconstructing the effects of
      environmental parameters, protein-based hydrogels serve as attractive, in vitro
      platforms to investigate cell-matrix interactions. For cell encapsulation, the
      process of hydrogel formation through physical or covalent cross-linking must be
      mild and cell compatible. While many chemical cross-linkers are commercially
      available for hydrogel formation, only a subset are cytocompatible; therefore,
      the identification of new and reliable cytocompatible cross-linkers allows for
      greater flexibility of hydrogel design for cell encapsulation applications. Here,
      we introduce tetrakis(hydroxymethyl) phosphonium chloride (THPC) as an
      inexpensive, amine-reactive, aqueous cross-linker for 3D cell encapsulation in
      protein-based hydrogels. We characterize the THPC-amine reaction by demonstrating
      THPC's ability to react with primary and secondary amines of various amino acids.
      In addition, we demonstrate the utility of THPC to tune hydrogel gelation time
      (6.7+/-0.2 to 27+/-1.2 min) and mechanical properties (storage moduli ~250 Pa to
      ~2200 Pa) with a recombinant elastin-like protein. Lastly, we show
      cytocompatibility of THPC for cell encapsulation with two cell types, embryonic
      stem cells and neuronal cells, where cells exhibited the ability to differentiate
      and grow in elastin-like protein hydrogels. The primary goal of this
      communication is to report the identification and utility of
      tetrakis(hydroxymethyl) phosphonium chloride (THPC) as an inexpensive but widely
      applicable cross-linker for protein-based materials.

PMID- 23151176
TI  - Lessons from 90 consecutive laparoscopic dismembered pyeloplasties in a residency
      program.
AB  - OBJECTIVE: The aim of this study was to report on the safety and efficacy of 90
      consecutive laparoscopic pyeloplasties carried out in a university hospital.
      MATERIAL AND METHODS: The outcomes of 90 transperitoneal dismembered
      pyeloplasties that were performed by residents at the hospital from March 2004 to
      March 2010 were analyzed. All of the surgeries were performed because of
      symptomatic ureteropelvic junction obstruction. The laparoscopic Anderson-Hynes
      dismembered technique was used in all cases, and a double-J stent was routinely
      placed and left in place for 4 weeks. The patients were followed up clinically
      and with imaging studies. Clinical data, outcomes and complication rates for the
      patients were retrospectively reviewed using a prospectively maintained database.
      RESULTS: The mean patient age was 38.9 (10-80) years, and 46 patients (51.1%)
      were males. The mean operative time was 222.5 (125-400) min. The surgery was
      completed laparoscopically in 96.6% of cases (87 patients). Conversion was
      required owing to technical difficulties in three cases. Overall, four (4.4%)
      patients had major complications. Seventy-six of the 87 patients (87.3%)
      presented improvements in symptomatology at a median follow-up of 39.7 (6-75)
      months. CONCLUSION: Laparoscopic pyeloplasty is feasible and associated with high
      success and low complication rates, even in a residency program.

PMID- 23151177
TI  - Renoprevention: A new concept for reengineering nephrology care--an economic
      impact and patient outcome analysis of two hypothetical patient management
      paradigms in the CCU.
AB  - BACKGROUND: The impact of acute kidney injury (AKI) on chronic kidney disease
      (CKD) progression remains uncertain; the common belief is that AKI in CKD is
      short-lived with subsequent full recovery. However 25.2% of end-stage renal
      disease (ESRD) Medicare patients all experienced antecedent AKI. We recently
      described a new syndrome of ESRD following AKI, the syndrome of rapid-onset end
      stage renal disease (SORO-ESRD). Renoprevention, which we described in 2009, is
      the application of preventative measures to reduce AKI incidence. METHODS: This
      is a descriptive study based on real clinical experience. Two hypothetical 69
      year-old Caucasian male patients, A and B, with symptomatic coronary artery
      disease (CAD) presented for elective cardiac catheterization and subsequent
      coronary artery bypass graft procedures; renoprevention was applied in patient A
      but not in B. RESULTS: Aggressive fluid repletion, withholding Lisinopril 40 mg
      once daily (QD) 1 week before hospitalization (hydralazine substituted) in A
      earlier discharge after 6 days, transient minimal change in serum creatinine.
      Patient B continued on Lisinopril 40 mg QD, experienced prolonged hypotension
      needing pressors-severe oliguric AKI, volume overload, daily RRT for 6 days,
      recovered kidney function, was discharged after 20 days. Hospital charges were
      $68,580 (A) versus $154,650 (B). If patient B had developed ESRD (SORO-ESRD), the
      savings would be humongous. CONCLUSION: A more forceful and pragmatic application
      of renoprevention strategies in the coronary care unit (CCU)-preemptive
      withholding of nephrotoxics including renin angiotensin aldosterone system (RAAS)
      blockers, aggressive prevention of perioperative hypotension, avoiding
      nephrotoxic exposure as contrast, and antibiotics-leads to less AKI, potentially
      less SORO-ESRD, better patient outcomes, and massive dollar savings. Such
      paradigm shifts would constitute major rethinking in current nephrology practice,
      a form of nephrology practice reengineering.

PMID- 23151178
TI  - Improved outcome for children with non-high risk acute lymphoblastic leukaemia
      after using an ALL IC-BFM 2002-based protocol in Shanghai, China.
AB  - We report the outcome of 92 non-high risk children with acute lymphoblastic
      leukaemia (ALL) following a Berlin-Frankfurt-Munster (BFM) Intercontinental ALL 
      based protocol. Compared with a matched historical control group, we found a
      lower incidence of treatment-related early death (1.2% vs. 10.9%, P = 0.015), a
      higher 6-year event-free survival (75.4 +/- 4.9% vs. 58.2 +/- 6.7%, P = 0.02),
      reduced total in-hospital costs per person (US $) (10267.0 vs. 18331.0, P <
      0.001) and fewer total in-hospital days (164 vs. 296, P < 0.001). This ALL-BFM
      based protocol was quite tolerable in our institution and will be extended to
      high-risk patients.

PMID- 23151180
TI  - Anisotropic epitaxial ZnO/CdO core/shell heterostructure nanorods.
AB  - Various surface structures and polarities of one-dimensional nanostructures
      offer additional control in synthesizing heterostructures suitable for
      optoelectronic and electronic applications. In this work, we report synthesis and
      characterization of ZnO-CdO nanorod-based heterostructures grown on a-plane
      sapphire. The heterojunction formed on the sidewall surface of the nanorod shows
      that wurtzite ZnO {1010} planes are interfaced with rocksalt CdO {100}. This is
      evidently different from the heterojunction formed on the nanorod top surface,
      where a ZnO (0001) top plane is interfaced with a CdO (111) plane. Such
      anisotropic heterostructures are determined by different surface structures of
      the nanorods and their polarities. Revelation of such anisotropic heterojunctions
      will provide a clue for understanding charge transport properties in electronic
      and optoelectronic nanodevices.

PMID- 23151179
TI  - High-resolution genome-wide scan of genes, gene-networks and cellular systems
      impacting the yeast ionome.
AB  - BACKGROUND: To balance the demand for uptake of essential elements with their
      potential toxicity living cells have complex regulatory mechanisms. Here, we
      describe a genome-wide screen to identify genes that impact the elemental
      composition ('ionome') of yeast Saccharomyces cerevisiae. Using inductively
      coupled plasma - mass spectrometry (ICP-MS) we quantify Ca, Cd, Co, Cu, Fe, K,
      Mg, Mn, Mo, Na, Ni, P, S and Zn in 11890 mutant strains, including 4940 haploid
      and 1127 diploid deletion strains, and 5798 over expression strains. RESULTS: We
      identified 1065 strains with an altered ionome, including 584 haploid and 35
      diploid deletion strains, and 446 over expression strains. Disruption of protein
      metabolism or trafficking has the highest likelihood of causing large ionomic
      changes, with gene dosage also being important. Gene over expression produced
      more extreme ionomic changes, but over expression and loss of function phenotypes
      are generally not related. Ionomic clustering revealed the existence of only a
      small number of possible ionomic profiles suggesting fitness tradeoffs that
      constrain the ionome. Clustering also identified important roles for the
      mitochondria, vacuole and ESCRT pathway in regulation of the ionome. Network
      analysis identified hub genes such as PMR1 in Mn homeostasis, novel members of
      ionomic networks such as SMF3 in vacuolar retrieval of Mn, and cross-talk between
      the mitochondria and the vacuole. All yeast ionomic data can be searched and
      downloaded at http://www.ionomicshub.org. CONCLUSIONS: Here, we demonstrate the
      power of high-throughput ICP-MS analysis to functionally dissect the ionome on a
      genome-wide scale. The information this reveals has the potential to benefit both
      human health and agriculture.

PMID- 23151182
TI  - The interplay between the gut immune system and microbiota in health and disease:
      nutraceutical intervention for restoring intestinal homeostasis.
AB  - Gut immune system is daily exposed to a plethora of antigens contained in the
      environment as well as in food. Both secondary lymphoid tissue, such as Peyer's
      patches, and lymphoid follicles (tertiary lymphoid tissue) are able to respond to
      antigenic stimuli releasing cytokines or producing antibodies (secretory IgA).
      Intestinal epithelial cells are in close cooperation with intraepithelial
      lymphocytes and possess Toll-like receptors on their surface and Nod-like
      receptors (NLRs) which sense pathogens or pathogen-associated molecular patterns.
      Intestinal microbiota, mainly composed of Bacteroidetes and Firmicutes, generates
      tolerogenic response acting on gut dendritic cells and inhibiting the T helper
      (h)-17 cell anti-inflammatory pathway. This is the case of Bacteroides fragilis
      which leads to the production of interleukin-10, an anti-inflammatory cytokine,
      from both T regulatory cells and lamina propria macrophages. Conversely,
      segmented filamentous bacteria rather induce Th17 cells, thus promoting
      intestinal inflammation. Intestinal microbiota and its toxic components have been
      shown to act on both Nod1 and Nod2 receptors and their defective signaling
      accounts for the development of inflammatory bowel disease (IBD). In IBD a loss
      of normal tolerance to intestinal microbiota seems to be the main trigger of
      mucosal damage. In addition, intestinal microbiota thanks to its regulatory
      function of gut immune response can prevent or retard neoplastic growth. In fact,
      chronic exposure to environmental microorganisms seems to be associated with low
      frequency of cancer risk. Major nutraceuticals or functional foods employed in
      the modulation of intestinal microbiota are represented by prebiotics,
      probiotics, polyunsaturated fatty acids, amino acids and polyphenols. The
      cellular and molecular effects performed by these natural products in terms of
      modulation of the intestinal microbiota and mostly attenuation of the
      inflammatory pathway are described.

PMID- 23151181
TI  - Neurobehavioral function and low-level exposure to brominated flame retardants in
      adolescents: a cross-sectional study.
AB  - BACKGROUND: Animal and in vitro studies demonstrated a neurotoxic potential of
      brominated flame retardants, a group of chemicals used in many household and
      commercial products to prevent fire. Although the first reports of detrimental
      neurobehavioral effects in rodents appeared more than ten years ago, human data
      are sparse. METHODS: As a part of a biomonitoring program for environmental
      health surveillance in Flanders, Belgium, we assessed the neurobehavioral
      function with the Neurobehavioral Evaluation System (NES-3), and collected blood
      samples in a group of high school students. Cross-sectional data on 515
      adolescents (13.6-17 years of age) was available for the analysis. Multiple
      regression models accounting for potential confounders were used to investigate
      the associations between biomarkers of internal exposure to brominated flame
      retardants [serum levels of polybrominated diphenyl ether (PBDE) congeners 47,
      99, 100, 153, 209, hexabromocyclododecane (HBCD), and tetrabromobisphenol A
      (TBBPA)] and cognitive performance. In addition, we investigated the association
      between brominated flame retardants and serum levels of FT3, FT4, and TSH.
      RESULTS: A two-fold increase of the sum of serum PBDE's was associated with a
      decrease of the number of taps with the preferred-hand in the Finger Tapping test
      by 5.31 (95% CI: 0.56 to 10.05, p = 0.029). The effects of the individual PBDE
      congeners on the motor speed were consistent. Serum levels above the level of
      quantification were associated with an average decrease of FT3 level by 0.18
      pg/mL (95% CI: 0.03 to 0.34, p = 0.020) for PBDE-99 and by 0.15 pg/mL (95% CI:
      0.004 to 0.29, p = 0.045) for PBDE-100, compared with concentrations below the
      level of quantification. PBDE-47 level above the level of quantification was
      associated with an average increase of TSH levels by 10.1% (95% CI: 0.8% to
      20.2%, p = 0.033), compared with concentrations below the level of
      quantification. We did not observe effects of PBDE's on neurobehavioral domains
      other than the motor function. HBCD and TBBPA did not show consistent
      associations with performance in the neurobehavioral tests. CONCLUSIONS: This
      study is one of few studies and so far the largest one investigating the
      neurobehavioral effects of brominated flame retardants in humans. Consistently
      with experimental animal data, PBDE exposure was associated with changes in the
      motor function and the serum levels of the thyroid hormones.

PMID- 23151183
TI  - Effect of fibrin-binding synthetic oligopeptide on the healing of full-thickness
      skin wounds in streptozotocin-induced diabetic rats.
AB  - The aim of this study was to investigate whether topical application of fibrin
      binding oligopeptides derived from FN promotes wound healing in streptozotocin
      (STZ)-induced diabetic rats. Oligopeptides including fibrin-binding sequences
      (FF3: CFDKYTGNTYRV, FF5 : CTSRNRCNDQ) of FN repeats were synthesized. Each
      peptide was loaded in 15 x 15 mm fibrous alginate dressings, and the release
      kinetics of the peptides was evaluated using trinitrobenzene sulfonic acid for
      336 hours. Two full-thickness cutaneous wounds were prepared on the dorsal skin
      of each 75 diabetes induced rats. Each wound was divided into FF3-loaded alginate
      dressing group, FF5-loaded alginate dressing group, alginate dressing group and
      negative control group. Animals were sacrificed at day 0,3,7 and 14. The wound
      closure rate, inflammation degree, expression of TGF-beta1 and hydroxyproline
      contents were evaluated. Both FF3 and FF5 peptides were released rapidly within
      the first 24 hours. FF3-loaded dressing treated wounds closed significantly
      faster than other wounds at day 3. And at day 14, FF3- & FF5- loaded dressing
      treated wounds demonstrated less inflammatory cells infiltration than alginate
      dressing treated and negative group wounds. TGF-beta1 positive cells were more
      abundant in FF3-, FF5-treated alginate dressing treated wound at day 3 and 14. At
      last, the hyrdroxyproline contents in the FF3, FF5 group were higher at day 7 and
      day 14. Topical application of fibrin-binding domain synthetic oligopeptides from
      FN resulted in acceleration of full-thickness cutaneous wound healing in diabetic
      rats.

PMID- 23151185
TI  - Enhanced electrical conductivity of silver nanoparticles for high frequency
      electronic applications.
AB  - An enhancement in the electrical performance of low temperature screen-printed
      silver nanoparticles (nAg) has been measured at frequencies up to 220 GHz. We
      show that for frequencies above 80 GHz the electrical losses in coplanar
      waveguide structures fabricated using nAg at 350  degrees C are lower than those
      found in conventional thick film Ag conductors consisting of micrometer-sized
      grains and fabricated at 850  degrees C. The improved electrical performance is
      attributed to the better packing of the silver nanoparticles resulting in lower
      surface roughness by a factor of 3. We discuss how the use of silver
      nanoparticles offers new routes to high frequency applications on temperature
      sensitive conformal substrates and in sub-THz metamaterials.

PMID- 23151184
TI  - Overexpression of Snail is associated with lymph node metastasis and poor
      prognosis in patients with gastric cancer.
AB  - BACKGROUND: Epithelial-mesenchymal transition (EMT) plays a significant role in
      tumor progression and invasion. Snail is a known regulator of EMT in various
      malignant tumors. This study investigated the role of Snail in gastric cancer.
      METHODS: We examined the effects of silenced or overexpressed Snail using lenti
      viral constructs in gastric cancer cells. Immunohistochemical analysis of tissue
      microarrays from 314 patients with gastric adenocarcinoma (GC) was used to
      determine Snail's clinicopathological and prognostic significance. Differential
      gene expression in 45 GC specimens with Snail overexpression was investigated
      using cDNA microarray analysis. RESULTS: Silencing of Snail by shRNA decreased
      invasion and migration in GC cell lines. Conversely, Snail overexpression
      increased invasion and migration of gastric cancer cells, in line with increased
      VEGF and MMP11. Snail overexpression (>=75% positive nuclear staining) was also
      significantly associated with tumor progression (P < 0.001), lymph node
      metastases (P = 0.002), lymphovascular invasion (P = 0.002), and perineural
      invasion (P = 0.002) in the 314 GC patients, and with shorter survival (P =
      0.023). cDNA microarray analysis revealed 213 differentially expressed genes in
      GC tissues with Snail overexpression, including genes related to metastasis and
      invasion. CONCLUSION: Snail significantly affects invasiveness/migratory ability
      of GCs, and may also be used as a predictive biomarker for prognosis or
      aggressiveness of GCs.

PMID- 23151186
TI  - Rapid and accurate detection of RMP- and INH- resistant Mycobacterium
      tuberculosis in spinal tuberculosis specimens by CapitalBioTM DNA microarray: a
      prospective validation study.
AB  - BACKGROUND: DNA microarrays can detect tuberculosis and its multi-drug resistant
      form in M. tuberculosis isolates and sputum specimens with high sensitivity and
      specificity. However, no performance data currently exists for its use in spinal
      tuberculosis specimens. This study was aimed to assess the performance of the
      CapitalBioTM DNA microarray in the detection of isoniazid (INH) and rifampicin
      (RMP) resistance in spinal tuberculosis compared with the BACT/MGIT 960 system.
      METHODS: From March 2009 to December 2011, 153 consecutive patients from
      Southwest Hospital, Chongqing with clinically and pathologically diagnosed spinal
      tuberculosis were enrolled into this study. Specimens collected during surgery
      from the tuberculosis patients were subjected to M. tuberculosis species
      identification and drug-resistance detection by the CapitalBioTM DNA microarray,
      and results were compared with those obtained from the absolute concentration
      drug susceptibility testing. RESULTS: The CapitalBioTM DNA microarray achieved
      93.55% sensitivity for the correct M. tuberculosis species identification of the
      93 specimens that tested positive for spinal tuberculosis through culture. In
      addition, twenty-seven additional patients (45.0%) were detected by the DNA
      microarray to be positive for M. tuberculosis among sixty spinal tuberculosis
      patients who were culture negative. Moreover, the DNA microarray had a
      sensitivity of 88.9% and a specificity of 90.7% for RMP resistance, and the
      microarray had a sensitivity of 80.0% and a specificity of 91.0% for INH
      resistance. The mean turn-around time of M. tuberculosis species identification
      and drug resistance detection using the DNA microarray was 5.8 (range, 4-9)
      hours. CONCLUSIONS: The CapitalBioTM DNA microarray is a feasible and accurate
      tool for the species identification of M. tuberculosis and for directly detecting
      RMP and INH resistance from spinal tuberculosis specimens in fewer than 9 hours.

PMID- 23151187
TI  - Role of neutral lipids in tear fluid lipid layer: coarse-grained simulation
      study.
AB  - Tear fluid lipid layer (TFLL) residing at the air-water interface of tears has
      been recognized to play an important role in the development of dry eye syndrome.
      Yet, the composition, structure, and mechanical properties of TFLL are only
      partly known. Here, we report results of coarse-grained simulations of a lipid
      layer comprising phospholipids, free fatty acids, cholesteryl esters, and
      triglycerides at the air-water interface to shed light on the properties of TFLL.
      We consider structural as well as dynamical properties of the lipid layer as a
      function of surface pressure. Simulations revealed that neutral lipids reside
      heterogeneously between phospholipids at relatively low pressures but form a
      separate hydrophobic phase with increasing surface pressure, transforming the
      initial lipid monolayer to a two-layered structure. When the model of TFLL was
      compared to a one-component phospholipid monolayer system, we found drastic
      differences in both structural and dynamical properties that explain the
      prominent role of neutral lipids as stabilizers of the TFLL. Based on our
      results, we suggest that neutral lipids are able to increase the stability of the
      TFLL by modulating its dynamical and structural behavior, which is important for
      the proper function of tear film.

PMID- 23151189
TI  - Novel prostaglandin receptor modulators: a patent review (2002 - 2012) - part I:
      non-EP receptor modulators.
AB  - INTRODUCTION: Prostaglandins and their G-protein coupled receptors play numerous
      physiological and pathophysiological roles especially in inflammation and its
      resolution. The variety of physiological effects mediated by prostanoids makes
      prostanoid receptors valuable drug targets and the research on prostaglandin
      receptor modulators is intensive. Prostaglandin receptor targeting drugs might be
      beneficial for the treatment of inflammatory, allergic, respiratory and
      cardiovascular disorders as well as treatment of pain but several novel fields of
      use such as cancer and ophthalmic diseases have also been found apart from these
      classical indications. AREAS COVERED: Evaluation of the patent activity over the
      last decade (2002 - 2012) illustrates many potent and selective modulators of the
      distinct prostanoid receptors and some novel methods for their use besides the
      classical indications. By now, some prostaglandin receptor antagonists already
      have reached clinical development. EXPERT OPINION: Though the structural
      diversity of compounds targeting prostanoid receptors is not really large,
      several highly potent agents with favorable properties have been developed. The
      clinical potential of FP, IP, TP and DP modulators remains to be investigated,
      while first very promising clinical results are available as far as CRTH2 is
      concerned.

PMID- 23151188
TI  - Nitrogen fertilization of the host plant influences production and pathogenicity
      of Botrytis cinerea secondary inoculum.
AB  - The influence of nitrogen (N) nutrition on a plant's susceptibility to Botrytis
      spp. and other pathogens is well documented. However, little is known of possible
      effects on sporulation of the pathogen on diseased tissue and on the
      pathogenicity of resulting secondary inoculum. To address this question,
      sporulation by two strains of Botrytis cinerea was quantified on tomato plants
      produced under different N irrigation regimes with inputs of NO(3)- at 0.5 to 45
      mmol liter(-1) (mM). Sporulation decreased significantly (P < 0.05) with
      increasing N fertilization up to NO(3)- at 15 to 30 mM. The secondary inoculum
      was collected and used to inoculate pruning wounds on tomato plants produced
      under a standard fertilization regime. Pathogenicity of the spores was
      significantly influenced by the nutritional status of their production substrate.
      Disease severity was highest with spores produced on plants with very low or very
      high N fertilization (NO(3)- at 0.5 or 30 mM). It was lowest for inoculum from
      plants with moderate levels of N fertilization. These results suggest that it may
      be possible to find an optimum level of N fertilization to reduce the production
      of secondary inoculum and its pathogenicity to tomato.

PMID- 23151190
TI  - Systemic associations of dynamic retinal vessel analysis: a review of current
      literature.
AB  - Endothelial dysfunction is a key pathogenic mechanism of CVD. The retinal
      microvascular network offers a unique, non-invasive window to study endothelial
      function. Recently, dynamic measurement of retinal vessel caliber using flicker
      light stimulation has been used to evaluate potential endothelial dysfunction and
      other mechanisms in CVD. A variety of studies now indicate that retinal
      vasodilation during flicker light simulation is reduced in diabetes,
      hypertension, hyperlipidemia and obesity, and may be influenced by age and
      race/ethnicity. These data suggest that flicker light-induced retinal
      vasodilation may be a unique and non-invasive measure of endothelial dysfunction.
      This review focuses recent studies on systemic associations of flicker light
      induced retinal vasodilation, and discusses the potential for future research in
      this area.

PMID- 23151192
TI  - Allergic contact dermatitis caused by a black permanent marker.

PMID- 23151191
TI  - Effect of persistency of first-line HIV antiretroviral therapy on clinical
      outcomes.
AB  - Persistency is the time from initiation to discontinuation of therapy. Previous
      research has described factors that affect the persistency of initial
      antiretroviral therapy (ART); however, the impact of persistency on clinical
      outcomes is unknown. A retrospective study was conducted of treatment-naive HIV
      patients initiating ART between January 1, 2000 and December 31, 2010 at an
      academic medical center. Descriptive statistics and Cox proportional hazards
      regression models with persistency as a time-varying covariate were fit for (1)
      immunologic failure (subsequent CD4 lower than initial CD4); (2) development of
      an opportunistic infection (OI) or malignancy; and (3) mortality. Analyses were
      repeated with an interaction term of persistency (per 180 days) and time (before
      and after 1 year of ART). Among 879 patients who started ART, the mean age was 38
      years (+/-10) and most patients were racial/ethnic minority (59%), males (80%),
      and with baseline CD4 <200 cells/mm(3) (52%). There were 100 deaths, 94
      OIs/malignancy, and 183 immunologic failures; the mean persistency=723 days. In
      multivariable modeling, increased persistency decreased the overall and long-term
      hazard for immunologic failure (0.84 per 180 additional days; 0.70-1.00; 0.045).
      Increased persistency exhibited a potential trend toward decreased hazard for the
      occurrence of OI/malignancy (0.91; 0.80-1.03; 0.124) overall and after 1 year.
      Persistency exhibited a trend toward less risk of mortality in the first year of
      ART (0.42; 0.17-1.06; 0.067). In this study of the relationship between initial
      ART persistency and clinical outcomes, increased persistency was associated with
      a decreased hazard for the development of immunologic failure, a trend toward a
      decreased hazard for OI/malignancy, and a trend toward a decreased risk of first
      year mortality. Given these findings, the relationship between persistency and
      clinical outcomes merits further study.

PMID- 23151193
TI  - A case of anaphylaxis caused by macrogol 3350 after injection of a
      corticosteroid.

PMID- 23151194
TI  - Occupational allergic contact dermatitis caused by (R)-3-(2-chloro-1
      hydroxyethyl)-phenol.

PMID- 23151195
TI  - Facial allergic contact dermatitis caused by fragrance ingredients released by an
      electric shaver.

PMID- 23151196
TI  - Are reusable rubber gloves associated with latex allergy?

PMID- 23151197
TI  - Occupational allergic contact dermatitis caused by oxycodone.

PMID- 23151198
TI  - Nickel may be released from laptop computers.

PMID- 23151199
TI  - Allergic or irritant contact dermatitis after patch testing with alcohol--that is
      the point.

PMID- 23151201
TI  - Information on blinding in registered records of clinical trials.
AB  - Information on blinding is part of the data that should be provided upon
      registration of a trial at a clinical trials registry. Reporting of blinding is
      often absent or of low quality in published articles of clinical trials. This
      study researched the presence and quality of information on blinding in
      registered records of clinical trials and highlights the important role of data
      recording formats at clinical trial registries in ensuring high-quality
      registration.

PMID- 23151202
TI  - Stereoselective cascade double-annulations provide diversely ring-fused
      tetracyclic benzopyrones.
AB  - A cascade double-annulation strategy employing diverse pairs of zwitterions with
      3-formylchromones is presented that provides stereoselective access to complex
      tetracyclic benzopyrones. Different zwitterions incorporated different rings that
      include aza-, oxa-, and carbocycles fused to a common benzopyrone scaffold and in
      the process created three contiguous chiral centers including an all-carbon
      quaternary center with high efficiency and excellent stereoselectivity.

PMID- 23151203
TI  - Interferon stimulated genes and hepatitis C virus infection.
AB  - Hepatitis C Virus (HCV) is a major cause of chronic liver disease worldwide. In
      addition to viral and environmental behavioral factors, host genetic diversity is
      believed to contribute to the spectrum of the disease. The sequencing of the
      human genome, together with the development of high-throughput technologies that
      measure the function of the genome, have afforded unique opportunities to develop
      profiles that can distinguish and classify discrete subsets of a disease and
      predict a response to therapy. In 2011, 2 directly acting antivirals (DAAs) have
      been approved for chronic HCV genotype 1 infection, Telaprevir and Boceprevir,
      and open a new area for HCV therapy. These 2 NS3/4 protease inhibitors are given
      in combination with pegylated interferon and ribavirin. Several DAAs are in
      development. Since a significant number of patients will fail to respond to
      treatment, or will have significant side effects, it is of major interest to
      predict a response to treatment as early as possible. Several studies are ongoing
      to identify biomarkers that could predict treatment outcome in patients with
      hepatitis C before treatment. Many of the genes upregulated in the liver between
      nonresponders and responders codes molecules secreted in the serum and can
      constitute a logical functional approach for the development of serum markers
      predictors of response to treatment. In the next future, further studies have
      several challenges to fight. First, large prospective cohorts with well
      phenotyped patients and appropriate tissue controls are needed. For response to
      treatment, the appropriate definition of sustained response and the same
      treatment regimen have to be addressed. Furthermore, improved technology and
      analytical procedures and the use of large numbers of patients for validation are
      needed.

PMID- 23151204
TI  - Injectable hydrogels from segmented PEG-bisurea copolymers.
AB  - We describe the preparation of an injectable, biocompatible, and elastic
      segmented copolymer hydrogel for biomedical applications, with segmented
      hydrophobic bisurea hard segments and hydrophilic PEG segments. The segmented
      copolymers were obtained by the step growth polymerization of amino-terminated
      PEG and aliphatic diisocyanate. Due to their capacity for multiple hydrogen
      bonding within the hydrophobic segments, these copolymers can form highly stable
      gels in water at low concentrations. Moreover, the gels show shear thinning by a
      factor of 40 at large strain, which allows injection through narrow gauge
      needles. Hydrogel moduli are highly tunable via the physical cross-link density
      and the length of the hydrophilic segments. In particular, the mechanical
      properties can be optimized to match the properties of biological host tissues
      such as muscle tissue and the extracellular matrix.

PMID- 23151205
TI  - Application of bifidobacterial phytases in infant cereals: effect on phytate
      contents and mineral dialyzability.
AB  - Phytase activity was recently described in probiotic bifidobacterial strains,
      opening the possibilities for their use in foods, due to the generally regarded
      as safe/qualified presumption of safety status of these bacteria. Two raw
      materials for infant cereals (multicereal and gluten-free) were examined by
      measuring the myo-inositol phosphates content and the in vitro Ca, Fe, and Zn
      availability after a dephytinization process with purified phytases from
      Bifidobacterium longum spp. infantis and Bifidobacterium pseudocatenulatum.
      Treatment with both enzymes reduced the contents of phytate as compared to
      control samples (untreated or treated with fungal phytase) and led to increased
      levels of myo-inositol triphosphate. Dephytinization followed by an in vitro
      model of intestinal digestion increased the solubility of Zn. However, phytase
      treatment did not increase significantly the mineral dialyzability as compared to
      untreated samples. This is the first example of the application of purified
      bifidobacterial phytases in food processing and shows the potential of these
      enzymes to be used in products for human consumption.

PMID- 23151206
TI  - NRE: a tool for exploring neutral loci in the human genome.
AB  - BACKGROUND: Analyzing regions of the genome where genetic variation is free from
      the confounding effects of natural selection is essential for many population
      genetic studies. Several recent studies in humans have stressed the large effect
      of natural selection at linked neutral sites and have shown that the choice of
      putatively neutral regions can have a marked effect on estimates of demographic
      history. RESULTS: NRE (Neutral Region Explorer) provides a mechanism for the easy
      extraction and analysis of nearly neutral regions from the human genome. It can
      combine many genomic filters, including filters for selection, recombination
      rate, genetic distance to the nearest gene, percent overlap with annotated
      regions, and user-provided loci. The program implements a two-step filtering
      process for greater versatility, allowing users to compile a basic set of
      neutrality criteria, explore their effect, and use this knowledge to refine
      filtering. Results can be instantly downloaded in standard formats, along with
      summary and ranking statistics, or exported to genome browsers such as those from
      the 1000 Genomes and UCSC. The applicability and value of NRE are demonstrated
      through an example in the estimation of the ratio of chromosome X-to-autosomal
      effective population size using different strategies for the selection of neutral
      regions. CONCLUSIONS: The combined features of NRE make possible the sort of
      flexible, rigorous mining and analysis of neutral loci increasingly demanded by
      population genetic studies. NRE is available at http://nre.cb.bscb.cornell.edu.

PMID- 23151207
TI  - Increased risk of cancer mortality associated with cadmium exposures in older
      Americans with low zinc intake.
AB  - Cadmium (Cd) exposure has been associated with increased cancer risk, and zinc
      (Zn) appears to reduce that risk. However, little is known about the combined
      influence of Cd and Zn on cancer risk. The aim of this study was to examine
      relationships between Cd exposure, Zn intake, and cancer mortality risks. The
      analyses used 5204 subjects aged 50 yr or older from the Third National Health
      and Nutrition Examination Survey (NHANES III, 1988-1994) and the mortality follow
      up through December 31, 2006. Cox proportional hazards models were used to test
      associations. In total, 569 cancer deaths were recorded during an average follow
      up of 12.4 yr, including 155 from lung, 61 from prostate, and 26 from breast
      cancer. A positive association between Cd and cancer mortality risk was
      identified for both genders. Despite limited cause-specific deaths, the increased
      risk associated with Cd was significant for lung cancer in men. All-cause cancer
      mortality risk was significantly elevated among women with Zn intakes below the
      recommended dietary allowance (RDA) compared with women who met the RDA. The
      effect of low dietary Zn was not observed in men. Similar trends for prostate and
      breast cancer deaths were not significant. There was a significant inverse
      association between cancer deaths and the Zn-to-Cd ratio for both genders. Cd
      exposure is an important independent risk factor of cancer mortality in older
      Americans and the risk appears exaggerated in those with inadequate dietary Zn.
      Additional studies are required to elucidate the mechanism(s) by which Zn
      participates in the carcinogenic influence of Cd.

PMID- 23151208
TI  - Dibenzo[def,p]chrysene (DBC) suppresses antibody formation in spleen cells
      following oral exposures of mice.
AB  - Dibenzo[def,p]chrysene (DBC) is a potent environmental carcinogen in rodents,
      fish, and human cells examined in culture. There are numerous similarities
      between the patterns of cytochrome P-450 (P450) activation of DBC and its
      covalent binding to DNA and proteins with another polycyclic aromatic hydrocarbon
      (PAH), 7,12-dimethylbenz[a]anthracene (DMBA). Our lab has previously shown that
      DMBA produces immunosuppression in rodents and human cell systems. Therefore, the
      purpose of these studies was to examine the immunotoxicity of DBC in a rodent
      model that was found to be sensitive to the immunosuppressive effects of DMBA.
      Data showed that DBC had similar potency to DMBA in producing suppression of a T
      dependent antibody response (TDAR) and altered spleen cell subsets in a similar
      manner as DMBA when DMBA was given by gavage for 5 d in corn oil to mice at doses
      of 1-100 mg/kg total cumulative doses. T-cell-independent antigen (TNP-Ficoll)
      responses were quantitatively less sensitive to DBC suppression. It was also
      found that as with DMBA, DBC produced a persistent immunosuppression, which
      lasted for at least 4 wk following dosing with a novel pill method for self
      administration of DBC. In conclusion, DBC appears to possess many of the same
      characteristics of DMBA in terms of its immunotoxicity.

PMID- 23151210
TI  - Effect of pregnancy on the levels of blood cadmium, lead, and mercury for females
      aged 17-39 years old: data from National Health and Nutrition Examination Survey
      2003-2010.
AB  - Data from the National Health and Nutrition Examination survey for the years 2003
      2010 were used (n = 4700) to evaluate the effect of age, parity, body mass index
      (BMI), race/ethnicity, pregnancy, iron (Fe) storage status, smoking status, and
      fish/shellfish consumption on the levels of blood cadmium (Cd), lead (Pb), and
      total mercury (Hg)for females aged 17-39 years old. Regression analysis was used
      to fit models for each of the three metals. For all three metals, age was
      positively and BMI was negatively associated with levels of these metals in
      blood. Smokers had statistically significantly higher levels of Cd and Pb
      irrespective of race/ethnicity and Fe storage status as compared to nonsmokers.
      Novel to this study, pregnancy was found to be associated with significantly
      lower levels of Cd, Pb, and Hg irrespective of race/ethnicity and Fe storage
      status as compared to nonpregnant females. It is conceivable that pregnancy may
      thus accelerate clearance of these metals from blood. Fish/shellfish consumption
      was associated with higher levels of Hg but not with Cd levels.

PMID- 23151211
TI  - A critical examination of the time and workload involved in the design and
      delivery of an e-module in postgraduate clinical education.
AB  - BACKGROUND: Although there is increasing pressure on Universities to implement e
      learning, this 'glorious revolution' has been met with disappointing results and
      universities have struggled to engage academic staff, who are major stakeholders,
      with its use. Although literature suggests online teaching adds to traditional
      faculty workload, information surrounding the actual 'cost' to individuals is
      sparse. For academics involved in postgraduate clinical education, it is even
      more incomplete. Involvement can be a risky undertaking for academics unfamiliar
      with the resources required. AIMS: This study outlines staff resources required
      to create an e-module for busy, practicing clinicians. METHOD: Data (web
      analytics, email traffic, and work logs) was collected and statistical analysis
      performed outlining time involved, work patterns and responsibilities. RESULTS:
      Data analysis revealed 75% of academic time occurred out of normal office hours.
      Sixteen total staff hours (12 planning and four delivery) were required to
      support one hour student online activity. Technical responsibilities were
      essential throughout, but unpredictable. CONCLUSIONS: Universities struggle to
      engage staff with e-learning due to its unrecognized and (many academics believe)
      unsustainable workload. Avoiding 'traditional' workload assumptions that are
      inaccurate, this study provides academics and managers involved in clinical
      education clear guidance and an increased understanding of workload with a goal
      to inform practice.

PMID- 23151209
TI  - Development of PBPK models for PFOA and PFOS for human pregnancy and lactation
      life stages.
AB  - Perfluoroalkyl acid carboxylates and sulfonates (PFAA) have many consumer and
      industrial applications. Developmental toxicity studies in animals have raised
      concern about potential reproductive/developmental effects of perfluorooctanoic
      acid (PFOA) and perfluorooctane sulfonate (PFOS); however, in humans conflicting
      results have been reported for associations between maternal PFAA levels and
      these outcomes. Risk assessments and interpretation of available human data
      during gestation and lactation are hindered due to lack of a framework for
      understanding and estimating maternal, fetal, and neonatal pharmacokinetics (PK).
      Physiologically based pharmacokinetic (PBPK) models were developed for PFOA and
      PFOS for the gestation and lactation life stages in humans to understand how the
      physiological changes associated with development affect pharmacokinetics of
      these compounds in the mother, fetus, and infant. These models were derived from
      PBPK models for PFOA/PFOS that were previously developed for adult humans and
      rats during gestation and lactation and from existing human pregnancy and
      lactation models developed for other chemicals. The models simulated PFOA and
      PFOS concentrations in fetal, infant, and maternal plasma and milk, were compared
      to available data in humans, and also were used to estimate maternal exposure.
      The models reported here identified several research needs, which include (1) the
      identification of transporters involved in renal resorption to explain the
      multiyear half-lives of these compounds in humans, (2) factors affecting
      clearance of PFOA/PFOS during gestation and lactation, and (3) data to estimate
      clearance of PFOA/PFOS in infants. These models may help address concerns
      regarding possible adverse health effects due to PFOA/PFOS exposure in the fetus
      and infant and may be useful in comparing pharmacokinetics across life stages.

PMID- 23151212
TI  - Chronic kidney disease epidemiology collaboration equation accuracy in predicting
      peritoneal dialysis-delivered creatinine clearance.
AB  - INTRODUCTION: Measuring total (residual kidney plus peritoneal) creatinine
      clearance (CrCl) with 24-h urine and dialysate collections is recommended for
      peritoneal dialysis (PD) adequacy evaluation. Prediction equations applied in
      this instance could simplify the approach. Cockcroft-Gault and modification of
      diet in renal disease (MDRD) four (MDRD-4) and six (MDRD-6) variables equations
      have been tested in this setting, and conflicting results have been reported. The
      Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation is currently
      considered to be more sensitive than the established equations for kidney
      function estimation. However, its performance in PD adequacy evaluation has not
      been studied. Our aim was to assess CKD-EPI equation's performance in predicting
      total measured CrCl (MCC) in PD patients. MATERIAL AND METHODS: A group of 23
      consecutive PD patients, male/female: 5/18, median age: 66 (32-91) years, median
      time on PD 32 (2-126) months, were enrolled in the study. All were treated by
      automated PD (APD). Sixteen out of twenty-three had residual renal function
      (RRF). MCC was determined from 24-h dialysate and urine collections and also
      predicted by Cockcroft-Gault, MDRD (4 and 6), and CKD-EPI equations. RESULTS: CKD
      EPI and MDRD-6 estimation results were similar to MCC (9.01 +/- 3.90 and 9.54 +/-
      2.98 vs. 8.64 +/- 3.75 mL/min/1.73 m(2) p = 0.49 and 0.09, respectively). Neither
      the presence nor the volume of residual urine affected the accuracy of
      prediction. Cockcroft-Gault and MDRD-4 equations differed significantly from MCC
      and were not accurately predictive. CONCLUSION: CKD-EPI equation could be used
      with accuracy for predicting MCC in PD patients. Only MDRD-6 showed similar
      accuracy, whereas MDRD-4 and Cockcroft-Gault equations were found to be
      inappropriate in this setting.

PMID- 23151213
TI  - Study Protocol: establishing good relationships between patients and health care
      providers while providing cardiac care. Exploring how patient-clinician
      engagement contributes to health disparities between indigenous and non
      indigenous Australians in South Australia.
AB  - BACKGROUND: Studies that compare Indigenous Australian and non-Indigenous
      patients who experience a cardiac event or chest pain are inconclusive about the
      reasons for the differences in-hospital and survival rates. The advances in
      diagnostic accuracy, medication and specialised workforce has contributed to a
      lower case fatality and lengthen survival rates however this is not evident in
      the Indigenous Australian population. A possible driver contributing to this
      disparity may be the impact of patient-clinician interface during key
      interactions during the health care process. METHODS/DESIGN: This study will
      apply an Indigenous framework to describe the interaction between Indigenous
      patients and clinicians during the continuum of cardiac health care, i.e. from
      acute admission, secondary and rehabilitative care. Adopting an Indigenous
      framework is more aligned with Indigenous realities, knowledge, intellects,
      histories and experiences. A triple layered designed focus group will be employed
      to discuss patient-clinician engagement. Focus groups will be arranged by
      geographic clusters i.e. metropolitan and a regional centre. Patient informants
      will be identified by Indigenous status (i.e. Indigenous and non-Indigenous) and
      the focus groups will be convened separately. The health care provider focus
      groups will be convened on an organisational basis i.e. state health providers
      and Aboriginal Community Controlled Health Services. Yarning will be used as a
      research method to facilitate discussion. Yarning is in congruence with the oral
      traditions that are still a reality in day-to-day Indigenous lives. DISCUSSION:
      This study is nestled in a larger research program that explores the drivers to
      the disparity of care and health outcomes for Indigenous and non-Indigenous
      Australians who experience an acute cardiac admission. A focus on health status,
      risk factors and clinical interventions may camouflage critical issues within a
      patient-clinician exchange. This approach may provide a way forward to reduce the
      appalling health disadvantage experienced within the Indigenous Australian
      communities.

PMID- 23151216
TI  - Cosynthesis of cargo-loaded hydroxyapatite/alginate core-shell nanoparticles
      (HAP@Alg) as pH-responsive nanovehicles by a pre-gel method.
AB  - A new core-shell nanostructure consisting of inorganic hydroxyapatite (HAP)
      nanoparticles as the core and organic alginate as the shell (denoted as HAP@Alg)
      was successfully synthesized by a pre-gel method and applied to pH-responsive
      drug delivery systems (DDS). HAP@Alg nanoparticles have the advantages of
      hydroxyapatite and alginate, where hydroxyapatite provides pH-responsive
      degradability, and alginate provides excellent biocompatibility and COOH
      functionality. Through the subsequent addition of CaCl(2) and phosphate solutions
      to the alginate solution, HAP@Alg nanoparticles with controllable particle sizes
      (ranging from 160 to 650 nm) were obtained, and their core-shell structure was
      confirmed through transmission electron microscopy (TEM) observation. Rhodamine
      6G (R6G), a positively charged dye, was selected as a model drug for pH-sensitive
      DDS. R6G was encapsulated in the HAP/Alg nanoparticles upon synthesis, and its
      loading efficiency could reach up to approximately 63.0%. The in vitro release
      behavior of the loaded R6G at different pH values was systematically studied, and
      the results indicated that more R6G molecules were released at lower pH
      conditions. For example, after releasing for 8 h, the release amount of R6G at pH
      2.0 was 2.53-fold the amount at pH 7.4. We attributed this pH-sensitive release
      behavior to the dissolution of the HAP core in acidic conditions. The results of
      the MTT assay and confocal laser scanning microscopy indicated that the HAP@Alg
      were successfully uptaken by liver cancer cells (HepG2) without apparent
      cytotoxicity. The synthesized HAP@Alg nanoparticles show great potential as drug
      nanovehicles with high biocompatibility, enhanced drug loading, and pH-responsive
      features for future intracellular DDS.

PMID- 23151214
TI  - Functional genomics of fuzzless-lintless mutant of Gossypium hirsutum L. cv. MCU5
      reveal key genes and pathways involved in cotton fibre initiation and elongation.
AB  - BACKGROUND: Fuzzless-lintless cotton mutants are considered to be the ideal
      material to understand the molecular mechanisms involved in fibre cell
      development. Although there are few reports on transcriptome and proteome
      analyses in cotton at fibre initiation and elongation stages, there is no
      comprehensive comparative transcriptome analysis of fibre-bearing and fuzzless
      lintless cotton ovules covering fibre initiation to secondary cell wall (SCW)
      synthesis stages. In the present study, a comparative transcriptome analysis was
      carried out using G. hirsutum L. cv. MCU5 wild-type (WT) and it's near isogenic
      fuzzless-lintless (fl) mutant at fibre initiation (0 dpa/days post anthesis),
      elongation (5, 10 and 15 dpa) and SCW synthesis (20 dpa) stages. RESULTS:
      Scanning electron microscopy study revealed the delay in the initiation of fibre
      cells and lack of any further development after 2 dpa in the fl mutant.
      Transcriptome analysis showed major down regulation of transcripts (90%) at fibre
      initiation and early elongation (5 dpa) stages in the fl mutant. Majority of the
      down regulated transcripts at fibre initiation stage in the fl mutant represent
      calcium and phytohormone mediated signal transduction pathways, biosynthesis of
      auxin and ethylene and stress responsive transcription factors (TFs). Further,
      transcripts involved in carbohydrate and lipid metabolisms, mitochondrial
      electron transport system (mETS) and cell wall loosening and elongation were
      highly down-regulated at fibre elongation stage (5-15 dpa) in the fl mutant. In
      addition, cellulose synthases and sucrose synthase C were down-regulated at SCW
      biosynthesis stage (15-20 dpa). Interestingly, some of the transcripts (~50%)
      involved in phytohormone signalling and stress responsive transcription factors
      that were up-regulated at fibre initiation stage in the WT were found to be up
      regulated at much later stage (15 dpa) in fl mutant. CONCLUSIONS: Comparative
      transcriptome analysis of WT and its near isogenic fl mutant revealed key genes
      and pathways involved at various stages of fibre development. Our data implicated
      the significant role of mitochondria mediated energy metabolism during fibre
      elongation process. The delayed expression of genes involved in phytohormone
      signalling and stress responsive TFs in the fl mutant suggests the need for a
      coordinated expression of regulatory mechanisms in fibre cell initiation and
      differentiation.

PMID- 23151215
TI  - Late relapses following reduced intensity allogeneic transplantation in patients
      with multiple myeloma: a long-term follow-up study.
AB  - We analysed the long-term outcomes of 60 multiple myeloma patients who underwent
      reduced intensity allogeneic stem cell transplantation between August 2000 and
      March 2008. Regimens included fludarabine and melphalan conditioning (flu-mel
      regimen) for allogeneic haematopoietic cell transplant (HCT) or a planned tandem
      regimen consisting of high-dose melphalan conditioning for autograft followed by
      low-dose total body irradiation conditioning for allogeneic HCT (auto-allo
      regimen). Donors included human-leucocyte-antigen-matched siblings (n = 55) or
      matched unrelated donors (n = 5). With a median follow-up of 9.8 years, 7-year
      overall survival (OS) and progression-free survival (PFS) were 60% and 31%,
      respectively. By multivariate Cox regression analysis, disease status of complete
      response (CR) or partial response (PR) at transplant and the presence of chronic
      graft-versus-host disease were significantly associated with improved OS. Only
      disease status was significantly associated with improved PFS. We noted a
      surprising number of very late relapses, with six patients (10%) relapsing
      between 6 and 12 years post-transplant. Among the six late relapse patients, all
      were transplanted within 14 months of diagnosis, five had normal karyotypes, and
      five were in CR/PR. Our data provide additional evidence that, while survival may
      be extended by reduced intensity allogeneic transplant, ultimately, it may not
      offer a cure.

PMID- 23151218
TI  - Atmospheric PCDD/F concentrations in 38 cities of China monitored with pine
      needles, a passive biosampler.
AB  - Many studies have shown that pine needles are a good biomonitor for atmospheric
      concentrations of polychlorinated dibenzo-p-dioxins (PCDDs) and polychlorinated
      dibenzofurans (PCDFs). However, this biomonitor has not been tested in large
      areas, and the quantitative relationship between concentrations in pine needles
      and air has not been established. In the present study, we collected pine needles
      from 38 cities in China. The concentrations of 2,3,7,8-PCDD/Fs were measured by
      gas chromatography combined with high-resolution mass spectrometry. The total
      PCDD/F concentrations ranged from 5.4 to 330 pg/g dry weight of pine needles. The
      pine needles from cities located in central China and three major city
      agglomerations contained high concentrations of PCDD/Fs, while those from cities
      in the west and on the coast contained relatively low concentrations. Primary
      emission and diffusion processes were the main controls of the PCDD/F
      concentrations in pine needles. Homologue profiles of PCDD/Fs in pine needles
      were characterized by PCDFs/PCDDs >1 in the industrialized cities and <1 in
      unindustrialized cities. The congener patterns were dominated by 1,2,3,4,6,7,8
      HpCDF and OCDD, indicating that combustion was the major source of the PCDD/Fs.
      By comparing the PCDD/F concentrations in the pine needles and those in air, we
      established a preliminary linear relationship between them. Finally, the
      concentrations in air of PCDD/Fs in the 38 cities of China could be predicted
      from this relationship.

PMID- 23151217
TI  - Depressive symptoms in people with chronic physical conditions: prevalence and
      risk factors in a Hong Kong community sample.
AB  - BACKGROUND: Depression is predicted to become one of the two most burdensome
      diseases worldwide by 2020 and is common in people with chronic physical
      conditions. However, depression is relatively uncommon in Asia. Family support is
      an important Asian cultural value that we hypothesized could protect people with
      chronic physical conditions from developing depression. We investigated
      depressive symptom prevalence and risk factors in a Chinese sample with chronic
      medical conditions, focusing on the possible protective role of family
      relationships. METHODS: Data were obtained from the Hong Kong Jockey Club FAMILY
      Project cohort study in 2009-2011, which included 6,195 participants (age >=15)
      with self-reported chronic conditions. Depressive symptoms were recorded using
      the Patient Health Questionnaire-9 (PHQ-9). Demographic and lifestyle variables,
      stressful life events, perceived family support and neighborhood cohesion were
      assessed. Factors associated with a non-somatic (PHQ-6) depression score were
      also examined. RESULTS: The prevalence of depressive symptoms (PHQ-9 scores >=5)
      was 17% in those with one or more chronic conditions, and was more prevalent in
      women than in men (19.7% vs. 13.9%; p < 0.001). In multilevel analyses, life
      stress, number of chronic conditions and satisfaction with family support
      explained 43% of the variance in PHQ-9 scores (standardized regression
      coefficients of 0.46, 0.15, and -0.12 respectively, all p <0.001). Body mass
      index, problem alcohol drinking, physical activity, and unmarried status were
      significantly associated with PHQ-9 scores, although these associations were
      weak. Variables associated with depression explained 35% of the variance in non
      somatic (PHQ-6) depression scores. Satisfaction with family support played a
      stronger protective role against depressive symptoms (both PHQ-9 and PHQ-6
      scores) among women than men (p < 0.05). CONCLUSIONS: Acute life stress and the
      number of chronic conditions, together with socio-demographic factors, explain
      most variance in depressive symptoms among chronically ill Chinese individuals.
      Somatic items in the PHQ-9 increased the depression scores but they did not alter
      the pattern of predictors. Family support appears to be an important protective
      factor in Chinese cultures for individuals with chronic conditions.

PMID- 23151219
TI  - Optoelectronic characteristics of YAG phosphor-incorporated ZnO films deposited
      by ultrasonic spray pyrolysis.
AB  - This work presents a novel white light device. An yttrium aluminum garnet (YAG)
      phosphor-incorporated zinc oxide (ZnO) film is deposited on a slide glass
      substrate by ultrasonic spray pyrolysis. A nanoflower consisting of a hexagonal
      nanopetal is formed on the surfaces of the samples, and the sizes of the
      nanopetal are approximately 200 to 700 nm. Additionally, the nanopetal becomes
      blunted with an increasing incorporated amount of YAG. As the incorporated amount
      is 1.5 and 2.5 wt.%, the photoluminescence color of the YAG-incorporated ZnO film
      is nearly white, possibly contributing to the YAG emission and the band-to-deep
      level transition in the ZnO film.

PMID- 23151222
TI  - The correlates of psychological health among the Turkish unemployed:
      psychological burden of financial help during unemployment.
AB  - The purpose of this study is to examine the major determinants of psychological
      health during unemployment. With this in mind, 438 (17% female and 83% male)
      unemployed individuals were contacted through Turkey's State Employment Office.
      It was expected that the relationship between duration of unemployment and
      psychological wellbeing would be nonlinear. Additionally it was hypothesized that
      perceived social support would moderate the relationship between length of
      unemployment and psychological health. Further, we suggested that self-esteem
      would be related to psychological health and moderate the relationship between
      length of unemployment and psychological health. The results supported the
      curvilinearity hypothesis of the relationship between unemployment duration and
      psychological health as measured by General Health Questionnaire. However, social
      support was not found to moderate the relationship between unemployment duration
      and psychological health. The hypothesis that self-esteem would moderate the
      relationship between length of unemployment and psychological distress was not
      supported, although self-esteem was a strong negative determinant of
      psychological distress during unemployment. Regression analysis showed that the
      best predictors of psychological health were self-esteem, perceived social
      support and perceived adequacy of financial aid received from relatives.
      Interestingly, perceived adequacy of the financial aid was negatively related to
      psychological health. This result was contradictory with the previous literature
      pointing out that financial aid reduces the effects of poverty due to
      unemployment. The findings of this study are important since the relationship
      between unemployment duration and psychological health was nonlinear, indicating
      that relevant services should be especially careful to intervene to increase
      social support and self-esteem during these critical times. The other results and
      limitations are discussed. 

PMID- 23151223
TI  - Repeptization by dissolution in a colloidal system of iron(III) pyrophosphate.
AB  - Repeptization (redispersion) from an aggregated state is usually only possible in
      charge-stabilized colloidal systems if the system is either coagulated in the
      secondary minimum of the interaction potential or if the system cannot settle
      completely into the primary minimum. In this work, we analyze the zeta potential,
      conductivity, and long-term stability of colloidal systems of iron(III)
      pyrophosphate and surprisingly find that the system seems to defy conventional
      wisdom as it can be repeptized from its coagulated state regardless of aging time
      and background ions. Moreover, after having been stored for up to a month in 2 M
      NaCl, dialysis of iron pyrophosphate will yield a colloidal dispersion that is
      actually stable for a longer period of time than a fresh system with background
      electrolyte removed.

PMID- 23151221
TI  - Multivitamin supplementation in HIV infected adults initiating antiretroviral
      therapy in Uganda: the protocol for a randomized double blinded placebo
      controlled efficacy trial.
AB  - BACKGROUND: Use of multivitamin supplements during the pre-HAART era has been
      found to reduce viral load, enhance immune response, and generally improve
      clinical outcomes among HIV-infected adults. However, immune reconstitution is
      incomplete and significant mortality and opportunistic infections occur in spite
      of HAART. There is insufficient research information on whether multivitamin
      supplementation may be beneficial as adjunct therapy for HIV-infected individuals
      taking HAART. We propose to evaluate the efficacy of a single recommended daily
      allowance (RDA) of micronutrients (including vitamins B-complex, C, and E) in
      slowing disease progression among HIV-infected adults receiving HAART in Uganda.
      METHODS/DESIGN: We are using a randomized, double-blind, placebo-controlled trial
      study design. Eligible patients are HIV-positive adults aged at least 18 years,
      and are randomized to receive either a placebo; or multivitamins that include a
      single RDA of the following vitamins: 1.4 mg B1, 1.4 mg B2, 1.9 mg B6, 2.6 mcg
      B12, 18 mg niacin, 70 mg C, 10 mg E, and 0.4 mg folic acid. Participants are
      followed for up to 18 months with evaluations at baseline, 6, 12 and 18 months.
      The study is primarily powered to examine the effects on immune reconstitution,
      weight gain, and quality of life. In addition, we will examine the effects on
      other secondary outcomes including the risks of development of new or recurrent
      disease progression event, including all-cause mortality; ARV regimen change from
      first- to second-line therapy; and other adverse events as indicated by incident
      peripheral neuropathy, severe anemia, or diarrhea. DISCUSSIONS: The conduct of
      this trial provides an opportunity to evaluate the potential benefits of this
      affordable adjunct therapy (multivitamin supplementation) among HIV-infected
      adults receiving HAART in a developing country setting. TRIAL REGISTRATION:
      Clinical Trial Registration-URL: http://www.clinicaltrials.gov. Unique
      identifier: NCT01228578.

PMID- 23151220
TI  - Characteristics of CD44 alternative splice pattern in the course of human
      colorectal adenocarcinoma progression.
AB  - BACKGROUND: CD44 is considered as 'a' metastasis associated gene, despite the
      fact that it is an umbrella term for a group of molecules produced from a single
      gene by alternative splicing. However, little consideration is given to the above
      in the literature of colorectal carcinomas as well as other tumour types, leading
      to confusion and contradictory results about its possible role in tumour
      progression. METHODS: We compared the CD44 alternative splice pattern (ASP) of
      three genetically different human colorectal cancer cell lines (HT25, HT29,
      HCT116) using a series of PCR reactions and next- generation sequencing method,
      as well as identified a colorectal adenocarcinoma specific CD44 ASP. This ASP was
      further investigated in terms of its qualitative and quantitative stability in
      our experimental iso- and xenograft mouse models for colorectal cancer
      progression. A complex preclinical experimental set-up was established to
      separately test the different steps of tumour progression and the role of tumour
      microenvironment, respectively, focusing on the role of 'CD44' in this process.
      RESULTS: We managed to present a colorectal cancer-specific CD44 ASP, which
      remained unchanged from cell lines throughout primary tumour formation and
      metastatic progression. Furthermore, we report a unique roster of all expressed
      CD44 variant isoforms characteristic to colorectal cancer. Finally, on
      quantitative assessment of the variable exons v3 and v6, higher co-expression
      levels were found to be characteristic to metastatically potent tumour cells.
      CONCLUSION: Particular CD44 variant isoforms seem to act as "metastasis genes"
      via tumour microenvironment-driven shifts in v3 and v6 expressions. However, this
      function may just affect a minority of tumour subclones. This fact and the huge
      potential number of different CD44 splice variants that can contain v3 and v6
      domains can explain incoherence of clinical studies regarding functional
      asessment of CD44 variants, as well as diminish the chances of using CD44
      variants for predictive purpose.

PMID- 23151224
TI  - Not as transient: patients with transient ischaemic attack or minor stroke
      experience cognitive and communication problems; an exploratory study.
AB  - BACKGROUND: Patients with transient ischaemic attack (TIA) or minor stroke
      generally receive, besides secondary prevention, no regular follow up care after
      discharge directly home from the Emergency Room or TIA outpatient clinic; because
      it is believed that they will experience no consequences. OBJECTIVES: To explore
      whether the TIA and minor stroke patients have persistent problems due to the
      event. METHODS: This study has a cross-sectional, comparative non-randomized,
      exploratory design. Patients with TIA or minor stroke, not requiring hospital
      admission, and a control group of stroke patients, recently discharged home, were
      selected and interviewed with a questionnaire by telephone or home visit, between
      one and eight months after the event. Patients with angina pectoris (AP) were
      recruited as a second control group. RESULTS: Data showed that 51% of the TIA and
      minor stroke patients and 71% of the stroke patients experienced five or more
      problems, as opposed to 32% of patients with AP. Between 39 and 49% of the TIA,
      minor stroke and the stroke patients reported cognitive and communicative
      difficulties. Moreover, the TIA and minor stroke patients had more cognitive
      deficits (n = 27, 49%) and communicative limitations (n = 23, 42%) than the AP
      group (n = 7, 10% and n = 4, 6%, respectively). CONCLUSION: About half of the TIA
      and minor stroke patients experienced problems regarding cognition and
      communication, which were specific to the event. General practitioners should be
      aware of these potential problems and monitor patients regularly. Future research
      should focus on prognostic indicators to identify patients at risk.

PMID- 23151226
TI  - Spontaneous uterine rupture in a primigravid woman in the early third trimester
      attributed to adenomyosis: a case report and review of the literature.
AB  - We report a rare case of spontaneous uterine rupture of an unscarred uterus
      caused by adenomyosis in the early third trimester. A 33-year-old primigravid
      woman was referred to our department because of severe acute abdominal pain and
      signs and symptoms of hemorrhagic shock. Ultrasound exanimation performed at
      admission revealed a living, intrauterine fetus of 28 weeks gestational age with
      reduced amniotic fluid and presence of free peritoneal fluid. The fetal heart
      rate was non-reassuring with variable decelerations and severe fetal bradycardia.
      Emergency cesarean section revealed massive hemoperitoneum and complete rupture
      in the uterine fundus. Subtotal peripartum hysterectomy with conservation of
      adnexae was performed. Histological examination revealed adenomyosis at the site
      of uterine rupture.

PMID- 23151228
TI  - Assembly of spirooxindole derivatives via organocatalytic iminium-enamine cascade
      reactions.
AB  - The assembly of complex spirocyclopentaneoxindoles via a novel organocatalytic
      iminium-enamine cascade process is reported. Reactions between 3-substituted
      oxindoles and alpha,beta-unsaturated aldehydes catalyzed by second generation
      prolinol ethers provided the desired products in high yield with excellent levels
      of enantioselectivity in a single step.

PMID- 23151227
TI  - Treatment-emergent adverse events after infusion of adherent stem cells: the
      MiSOT-I score for solid organ transplantation.
AB  - BACKGROUND: Cellular therapy after organ transplantation is emerging as an
      intriguing strategy to achieve dose reduction of classical immunosuppressive
      pharmacotherapy. Here, we introduce a new scoring system to assess treatment
      emergent adverse events (TEAEs) of adherent stem cell therapies in the clinical
      setting of allogeneic liver transplantation (for example, the MiSOT-I trial
      Eudract CT: 2009-017795-25). METHODS: The score consists of three independent
      modalities (set of parameters) that focus on clinically relevant events early
      after intravenous or intraportal stem cell infusion: pulmonary toxicity,
      intraportal-infusional toxicity and systemic toxicity. For each modality, values
      between 0 (no TEAE) and 3 (severe TEAE) were defined. The score was validated
      retrospectively on a cohort of n=187 recipients of liver allografts not receiving
      investigational cell therapy between July 2004 and December 2010. These patients
      represent a control population for further trials. Score values were calculated
      for days 1, 4, and 10 after liver transplantation. RESULTS: Grade 3 events were
      most commonly related to the pulmonary system (3.5% of study cohort on day 4).
      Almost no systemic-related TEAEs were observed during the study period. The
      relative frequency of grade 3 events never exceeded 5% over all modalities and
      time points. A subgroup analysis for grade 3 patients provided no descriptors
      associated with severe TEAEs. CONCLUSION: The MiSOT-I score provides an
      assessment tool to score specific adverse events that may occur after adherent
      stem cell therapy in the clinical setting of organ transplantation and is thus a
      helpful tool to conduct a safety study.

PMID- 23151229
TI  - Identification of a novel binding site between HIV type 1 Nef C-terminal flexible
      loop and AP2 required for Nef-mediated CD4 downregulation.
AB  - HIV-1 Nef is an accessory protein necessary for HIV-1 virulence and rapid AIDS
      development. Nef promotes viral replication and infection by connecting CD4 and
      several other cell surface receptors to the clathrin adaptor protein AP2,
      resulting in the internalization and degradation of the receptors interacting
      with Nef. We investigated how Nef can mediate constitutive receptor endocytosis
      through the interaction of the dileucine motif in its C-terminal flexible loop (C
      loop) with AP2, whereas AP2 binding of the transmembrane receptors usually
      results in an equilibrated (recycled) endocytosis. Our results indicated that in
      addition to the dileucine motif, there is a second motif in the Nef C-loop
      involved in the Nef-AP2 interaction. Nef-mediated CD4 downregulation was impaired
      when the residue in the hydrophobic region in the Nef C-loop (LL165HPMSLHGM173)
      was mutated to a basic residue K/R or an acidic residue E/D or to the rigid
      residue P, or when M168L170, L170H171, or G172M173 was mutated to AA. A pull-down
      assay indicated that AP2 was not coprecipitated with Nef mutants that did not
      downregulate CD4. Molecular modeling of the Nef C-terminal flexible loop in
      complex with AP2 suggests that M168L170 occupies a pocket in the AP2 sigma2
      subunit. Our data suggest a new model in the Nef-AP2 interaction in which the
      hydrophobic region in the Nef C-loop with the dileucine (L164L165) motif and
      M168L170 motif binds to AP2(sigma2), while the acidic motif E174 and D175 binds
      to AP2(alpha), which explains how Nef through the flexible loop connects CD4 to
      AP2 for constitutive CD4 downregulation.

PMID- 23151231
TI  - Cancer cell resistance to aurora kinase inhibitors: identification of novel
      targets for cancer therapy.
AB  - Drug resistance is the major obstacle to successful cancer therapy. Our study
      focuses on resistance to Aurora kinase inhibitors tested as anti-cancer drugs in
      clinical trials. We have used 2D electrophoresis in the pH ranges of 4-7 and 6-11
      followed by protein identification using MALDI-TOF/TOF to compare the protein
      composition of HCT116 colon cancer cells either sensitive to CYC116 and ZM447439
      inhibitors or resistant toward these drugs. The analysis also included p53(+/+)
      and p53(-/-) phenotypes of HCT116 cells. Our findings demonstrate that platelet
      activating factor acetylhydrolase and GTP-binding nuclear protein Ran contribute
      to the development of resistance to ZM447439 only where resistance is related to
      p53. On the other hand, serine hydroxymethyltransferase was found to promote the
      tumor growth in cells resistant to CYC116 without the influence of p53. Computer
      modeling of interaction networks highlighted a direct link of the p53-independent
      mechanism of resistance to CYC116 with autophagy. Importantly, serine
      hydroxymethyltransferase, serpin B5, and calretinin represent the target proteins
      that may help overcome resistance in combination therapies. In addition, serpin
      B5 and calretinin appear to be candidate biomarkers that may be accessible in
      patients for monitoring of cancer therapy with ease.

PMID- 23151232
TI  - Pros and cons of prognostic disclosure to Japanese cancer patients and their
      families from the family's point of view.
AB  - BACKGROUND: The primary goals of this analysis were to explore the pros and cons
      of prognostic disclosure to patients and their families from the bereaved
      family's point of view. METHODS: Semistructured interviews were conducted with 60
      bereaved family members of patients with cancer in Japan. RESULTS: There were
      eight categories of influence related to the disclosure of prognosis to the
      family, including pros (e.g., "Enabling mental preparedness for the patient's
      death") and cons (e.g., "Being distressed by acknowledging the patient's
      prognosis"); and seven categories of influence of not disclosing the prognosis to
      family, including pros (e.g., "Being able to maintain hope") and cons (e.g.,
      "Being prevented from providing adequate care for the patient"). There were also
      nine categories of influence related to the disclosure of prognosis to patients
      (e.g., "Enabling various discussions regarding death with the patient"), and
      eight categories of influence related to not disclosing the prognosis to patients
      (e.g., "Maintaining the patient's hope"). CONCLUSIONS: Although prognostic
      disclosure to family members can contribute to psychological distress and
      hopelessness, at the same time, it has the potential to prepare them for the
      future both emotionally and practically, and also to make the time until the
      patient's death as meaningful as possible. It is useful for physicians to
      introduce pros and cons of prognostic disclosure to family members at the time of
      decision making, to understand the family members' psychological state, and to
      provide support considering pros and cons whether or not they disclosed
      prognosis.

PMID- 23151233
TI  - PolySac3DB: an annotated data base of 3 dimensional structures of
      polysaccharides.
AB  - BACKGROUND: Polysaccharides are ubiquitously present in the living world. Their
      structural versatility makes them important and interesting components in
      numerous biological and technological processes ranging from structural
      stabilization to a variety of immunologically important molecular recognition
      events. The knowledge of polysaccharide three-dimensional (3D) structure is
      important in studying carbohydrate-mediated host-pathogen interactions,
      interactions with other bio-macromolecules, drug design and vaccine development
      as well as material science applications or production of bio-ethanol.
      DESCRIPTION: PolySac3DB is an annotated database that contains the 3D structural
      information of 157 polysaccharide entries that have been collected from an
      extensive screening of scientific literature. They have been systematically
      organized using standard names in the field of carbohydrate research into 18
      categories representing polysaccharide families. Structure-related information
      includes the saccharides making up the repeat unit(s) and their glycosidic
      linkages, the expanded 3D representation of the repeat unit, unit cell dimensions
      and space group, helix type, diffraction diagram(s) (when applicable),
      experimental and/or simulation methods used for structure description, link to
      the abstract of the publication, reference and the atomic coordinate files for
      visualization and download. The database is accompanied by a user-friendly
      graphical user interface (GUI). It features interactive displays of
      polysaccharide structures and customized search options for beginners and
      experts, respectively. The site also serves as an information portal for
      polysaccharide structure determination techniques. The web-interface also
      references external links where other carbohydrate-related resources are
      available. CONCLUSION: PolySac3DB is established to maintain information on the
      detailed 3D structures of polysaccharides. All the data and features are
      available via the web-interface utilizing the search engine and can be accessed
      at http://polysac3db.cermav.cnrs.fr.

PMID- 23151234
TI  - Aged rats are susceptible to nephrotoxicity induced by iodinated contrast media.
AB  - OBJECTIVE: The objective of this study is to evaluate the effect and mechanism of
      aging on iodinated-contrast-media-induced nephropathy in male rats. METHODS:
      Twenty-four healthy male rats were initially divided into 12-month-old and 24
      month-old age groups (adult and older age groups, respectively; n = 12/group);
      subsequently, each age group was randomly divided into saline control (NS) and
      contrast media (CM) groups (n = 6/group). CM (76% diatrizoate, 10 mL/kg b.w.) was
      given through the caudal vein. Urinary creatinine (Ucr) and serum creatinine
      (Scr) were detected by an automatic biochemical analyzer. The activities of renal
      malondialdehyde (MDA), superoxide dismutase (SOD), angiotensin-converting enzyme
      (ACE), angiotensin II (Ang II), and reduced form of nicotinamide adenine
      dinucleotide phosphate oxidase (NADPH oxidase) were determined by
      spectrophotometric assays with commercially available kits according to the
      manufacturers' protocols. Renal histological changes were observed by hematoxylin
      and eosin staining and scored semiquantitatively. RESULTS: In diatrizoate
      injected aged rats, Scr, the activities of ACE, Ang II, MDA, and NADPH oxidase in
      renal tissues were significantly increased (p < 0.01). The histologic scores were
      higher in the aged animals with CM treatment than those of control or adult rats
      (p < 0.01). There was an increasing trend but no significant statistical
      difference in renal ACE, Ang II, MDA, and NADPH oxidase or histologic scores in
      adult CM-injected rats compared with control animals (p > 0.05). CONCLUSIONS:
      Older age is an aggravating factor of iodinated-contrast-media-induced
      nephropathy in male rats. Oxidative stress and the renin-angiotensin system (RAS)
      may play an important role in nephrotoxicity induced by iodinated contrast media,
      especially in aged male rats.

PMID- 23151238
TI  - Effects of lifestyle modification on metabolic syndrome: a systematic review and
      meta-analysis.
AB  - BACKGROUND: To evaluate the effect of lifestyle modifications on metabolic
      syndrome (MetS) as assessed by its resolution and improved values for its
      components. METHODS: This was a systematic review and meta-analysis. Searches
      were performed of MEDLINE and the Cochrane Database from January 1966 to October
      2011 to identify randomized controlled trials (RCTs) related to the study
      objective. The included studies were RCTs restricted to the English language,
      with a follow-up period of 6 months or more, which reported overall resolution of
      MetS or values of MetS components (fasting blood glucose, waist circumference,
      high-density lipoprotein (HDL), triglycerides, and systolic and diastolic blood
      pressure (SBP, DBP)). Two investigators independently assessed study eligibility.
      The effect sizes were the relative proportion of patients with resolved MetS and
      mean differences in MetS component values from baseline to 1-year follow-up in a
      lifestyle-modification intervention (LMI) group versus a control (conventional
      lifestyle education or no treatment) group. Meta-analyses were conducted using a
      random-effects model. RESULTS: Eleven interventions in eight RCTs were used for
      the meta-analyses. The relative proportion of patients with resolved MetS in the
      intervention group was approximately 2.0 (95% CI 1.5 to 2.7) times greater in the
      intervention group compared with the control group (7 interventions, n = 2.839).
      LMI (5 interventions, n = 748) significantly reduced mean values for SBP by -6.4
      mmHg (95% CI -9.7 to -3.2), DBP by -3.3 mmHg (95% CI -5.2 to -1.4), triglycerides
      by -12.0 mg/dl (95% CI -22.2 to -1.7), waist circumference by -2.7 cm (95% CI 
      4.6 to -0.9), and fasting blood glucose by -11.5 mg/dl (95% CI -22.4 to -0.6) (5
      interventions), but reductions were not significant for HDL (1.3 mg/dl; 95% CI 
      0.6 to 3.1). CONCLUSIONS: The LMI was effective in resolving MetS and reducing
      the severity of related abnormalities (fasting blood glucose, waist
      circumference, SBP and DBP, and triglycerides) in subjects with MetS.

PMID- 23151237
TI  - Do self-report and medical record comorbidity data predict longitudinal
      functional capacity and quality of life health outcomes similarly?
AB  - BACKGROUND: The search for a reliable, valid and cost-effective comorbidity risk
      adjustment method for outcomes research continues to be a challenge. The most
      widely used tool, the Charlson Comorbidity Index (CCI) is limited due to frequent
      missing data in medical records and administrative data. Patient self-report data
      has the potential to be more complete but has not been widely used. The purpose
      of this study was to evaluate the performance of the Self-Administered
      Comorbidity Questionnaire (SCQ) to predict functional capacity, quality of life
      (QOL) health outcomes compared to CCI medical records data. METHOD: An SCQ-score
      was generated from patient interview, and the CCI score was generated by medical
      record review for 525 patients hospitalized for Acute Coronary Syndrome (ACS) at
      baseline, three months and eight months post-discharge. Linear regression models
      assessed the extent to which there were differences in the ability of comorbidity
      measures to predict functional capacity (Activity Status Index [ASI] scores) and
      quality of life (EuroQOL 5D [EQ5D] scores). RESULTS: The CCI (R2 = 0.245; p =
      0.132) did not predict quality of life scores while the SCQ self-report method
      (R2 = 0.265; p < 0.0005) predicted the EQ5D scores. However, the CCI was almost
      as good as the SCQ for predicting the ASI scores at three and six months and
      performed slightly better in predicting ASI at eight-month follow up (R2 = 0.370;
      p < 0.0005 vs. R2 = 0.358; p < 0.0005) respectively. Only age, gender, family
      income and Center for Epidemiologic Studies-Depression (CESD) scores showed
      significant association with both measures in predicting QOL and functional
      capacity. CONCLUSIONS: Although our model R-squares were fairly low, these
      results show that the self-report SCQ index is a good alternative method to
      predict QOL health outcomes when compared to a CCI medical record score. Both
      measures predicted physical functioning similarly. This suggests that patient
      self-reported comorbidity data can be used for predicting physical functional
      capacity and QOL and can serve as a reliable risk adjustment measure. Self-report
      comorbidity data may provide a cost-effective alternative method for risk
      adjustment in clinical research, health policy and organizational improvement
      analyses. TRIAL REGISTRATION: Clinical Trials.gov NCT00416026.

PMID- 23151239
TI  - Severe cutaneous toxicity related to Eltrombopag.

PMID- 23151230
TI  - Ion channel associated diseases: overview of molecular mechanisms.

PMID- 23151240
TI  - The large universal Pantoea plasmid LPP-1 plays a major role in biological and
      ecological diversification.
AB  - BACKGROUND: Pantoea spp. are frequently isolated from a wide range of ecological
      niches and have various biological roles, as plant epi- or endophytes, biocontrol
      agents, plant-growth promoters or as pathogens of both plant and animal hosts.
      This suggests that members of this genus have undergone extensive genotypic
      diversification. One means by which this occurs among bacteria is through the
      acquisition and maintenance of plasmids. Here, we have analyzed and compared the
      sequences of a large plasmid common to all sequenced Pantoea spp. RESULTS AND
      DISCUSSION: The Large PantoeaPlasmids (LPP-1) of twenty strains encompassing
      seven different Pantoea species, including pathogens and endo-/epiphytes of a
      wide range of plant hosts as well as insect-associated strains, were compared.
      The LPP-1 plasmid sequences range in size from ~281 to 794 kb and carry between
      238 and 750 protein coding sequences (CDS). A core set of 46 proteins,
      encompassing 2.2% of the total pan-plasmid (2,095 CDS), conserved among all LPP-1
      plasmid sequences, includes those required for thiamine and pigment biosynthesis.
      Phylogenetic analysis reveals that these plasmids have arisen from an ancestral
      plasmid, which has undergone extensive diversification. Analysis of the proteins
      encoded on LPP-1 also showed that these plasmids contribute to a wide range of
      Pantoea phenotypes, including the transport and catabolism of various substrates,
      inorganic ion assimilation, resistance to antibiotics and heavy metals,
      colonization and persistence in the host and environment, pathogenesis and
      antibiosis. CONCLUSIONS: LPP-1 is universal to all Pantoea spp. whose genomes
      have been sequenced to date and is derived from an ancestral plasmid. LPP-1
      encodes a large array of proteins that have played a major role in the adaptation
      of the different Pantoea spp. to their various ecological niches and their
      specialization as pathogens, biocontrol agents or benign saprophytes found in
      many diverse environments.

PMID- 23151241
TI  - Dose-dependent effect of antipsychotic drugs on autonomic nervous system activity
      in schizophrenia.
AB  - BACKGROUND: Antipsychotic drugs are considered a trigger factor for autonomic
      dysregulation, which has been shown to predict potentially fatal arrhythmias in
      schizophrenia. However, the dose-dependent effect of antipsychotic drugs and
      other psychotropic drugs on autonomic nervous system (ANS) activity remain
      unclear. The purpose of this study was to investigate the dose-dependent effect
      of antipsychotic drugs and other clinical factors on ANS activity in an adequate
      sample size of patients with schizophrenia. METHODS: A total of 211 Japanese
      patients with schizophrenia and 44 healthy subjects participated in this study.
      ANS activity was assessed by means of heart rate variability (HRV) power spectral
      analysis. Antipsychotic drug treatment and various clinical factors were
      investigated for each participant. The patient group was categorized into three
      subgroups according to daily dose of antipsychotic drug, and HRV was compared
      between groups. RESULTS: The results showed significantly decreased low-frequency
      and high-frequency components of HRV in the patient group compared to the control
      group. The high-dose group showed a significantly lower HRV than the medium-dose
      group and an even lower HRV than the low-dose group. In addition, a significant
      association between HRV and antipsychotic drug dose was identified by multiple
      regression analysis. HRV was not associated with age, sex, body mass index,
      duration of illness, or daily dose of other psychotropic drugs. CONCLUSION: These
      results suggest that antipsychotic drugs exert a significant dose-dependent
      effect on the extent of decline in ANS activity, and that optimal antipsychotic
      medication is required to avoid possible cardiovascular adverse events in
      patients with schizophrenia.

PMID- 23151243
TI  - Inhibition of uncoupling protein 2 with genipin exacerbates palmitate-induced
      hepatic steatosis.
AB  - BACKGROUND: Uncoupling protein 2 (UCP2) was reported to be involved in lipid
      metabolism through regulating the production of superoxide anion. However, the
      role of UCP2 in hepatocytes steatosis has not been determined. We hypothesized
      that UCP2 might regulate hepatic steatosis via suppressing oxidative stress.
      RESULTS: We tested this hypothesis in an in vitro model of hepatocytic steatosis
      in HepG2 cell lines induced by palmitic acid (PA). We found that treatment with
      PA induced an obvious lipid accumulation in HepG2 cells and a significant
      increase in intracellular triglyceride content. Moreover, the specific inhibition
      of UCP2 by genipin remarkably exacerbated PA-induced hepatocytes steatosis.
      Interestingly, the PA-induced superoxide overproduction can also be enhanced by
      incubation with genipin. In addition, administration with the antioxidant tempol
      abolished genipin-induced increase in intracellular lipid deposition. We further
      found that genipin significantly increased the protein expression of fatty acid
      translocase (FAT)/CD36. CONCLUSIONS: These findings suggest that UCP2 plays a
      protective role in PA-induced hepatocytic steatosis through ameliorating
      oxidative stress.

PMID- 23151245
TI  - Copper catalyzed N-arylation of amidines with aryl boronic acids and one-pot
      synthesis of benzimidazoles by a Chan-Lam-Evans N-arylation and C-H activation/C
      N bond forming process.
AB  - Mono-N-arylation of benzamidines 1 with aryl boronic acids 2 was effectively
      achieved in the presence of a catalytic amount of Cu(OAc)(2) and NaOPiv under
      mild aerobic conditions. Combining this step with an intramolecular direct C-H
      bond functionalization, catalyzed by the same catalytic system but under oxygen
      at 120  degrees C, afforded benzimidazoles 3 in good to excellent yields.

PMID- 23151244
TI  - Distribution and preliminary exposure assessment of bisphenol AF (BPAF) in
      various environmental matrices around a manufacturing plant in China.
AB  - Increasing attention has been paid to bisphenol A and bisphenol (BP) analogues
      due to high production volumes, wide usage and potential adverse effects.
      Bisphenol AF (BPAF) is considered a new bisphenol analogue which is used as raw
      material in plastic industry, but little is known about its occurrence in the
      environment and the potential associated risk. In this work, BPAF levels and
      environmental distribution were reported in samples collected around a
      manufacturing plant and a preliminary exposure risk assessment to local residents
      was conducted. BPAF was detected in most of the samples, with levels in river
      ranging between <LOD to 1.53 * 104 ng/L, sediments (0.520-2.00 * 103 ng/g dry
      weight, dw), soils (<LOD to 331 ng/g dw) and indoor dusts (7.82-739 ng/g dw) and
      well water (<LOD to 300 ng/L). Exponential declining trends were observed for
      BPAF levels with increasing distance from the manufacturing plant. Based on the
      quantitative data and quantitative structure-property relationship (QSPR) model
      deduction, BPAF was predicted to mainly retain in sediment and soil after
      released into the ambient environment and organic carbon was the domain factor
      during the process. The preliminary BPAF exposure assessment based on the CSOIL
      model suggested that children could have higher intake of BPAF than adults
      through inhalation of soils, dermal exposure by soils contact and bathing with
      well water.

PMID- 23151246
TI  - NICE clinical guideline (CG152): the management of Crohn's disease in adults,
      children and young people.
AB  - BACKGROUND: The guideline offers best practice advice on the care of adults,
      children and young people with Crohn's disease. AIM: To provide clinically
      effective and cost-effective evidence-based recommendations to guide clinical
      practice in a clinical guideline commissioned by the National Institute for
      Health and Clinical Excellence (NICE). METHODS: A systematic review of the
      evidence including critical appraisal, meta-analysis and cost-effectiveness
      modelling. RESULTS: Thirty-one evidence-based recommendations covering induction
      and maintenance therapy are available. Five key priorities for implementation are
      identified together with nine future research recommendations. Three guideline
      versions are available: short (containing just the recommendations), full
      (containing the full evidence base) and an Understanding NICE guidance for
      patients and carers. Algorithms have been produced together with a NICE pathway
      and implementation tools. CONCLUSION: These are the first evidence-based clinical
      and cost-effectiveness guidelines for Crohn's disease in the United Kingdom.

PMID- 23151247
TI  - Improved base-calling and quality scores for 454 sequencing based on a Hurdle
      Poisson model.
AB  - BACKGROUND: 454 pyrosequencing is a commonly used massively parallel DNA
      sequencing technology with a wide variety of application fields such as
      epigenetics, metagenomics and transcriptomics. A well-known problem of this
      platform is its sensitivity to base-calling insertion and deletion errors,
      particularly in the presence of long homopolymers. In addition, the base-call
      quality scores are not informative with respect to whether an insertion or a
      deletion error is more likely. Surprisingly, not much effort has been devoted to
      the development of improved base-calling methods and more intuitive quality
      scores for this platform. RESULTS: We present HPCall, a 454 base-calling method
      based on a weighted Hurdle Poisson model. HPCall uses a probabilistic framework
      to call the homopolymer lengths in the sequence by modeling well-known 454 noise
      predictors. Base-calling quality is assessed based on estimated probabilities for
      each homopolymer length, which are easily transformed to useful quality scores.
      CONCLUSIONS: Using a reference data set of the Escherichia coli K-12 strain, we
      show that HPCall produces superior quality scores that are very informative
      towards possible insertion and deletion errors, while maintaining a base-calling
      accuracy that is better than the current one. Given the generality of the
      framework, HPCall has the potential to also adapt to other homopolymer-sensitive
      sequencing technologies.

PMID- 23151248
TI  - A comprehensive model for intimate partner violence in South African primary
      care: action research.
AB  - BACKGROUND: Despite extensive evidence on the magnitude of intimate partner
      violence (IPV) as a public health problem worldwide, insubstantial progress has
      been made in the development and implementation of sufficiently comprehensive
      health services. This study aimed to implement, evaluate and adapt a published
      protocol for the screening and management of IPV and to recommend a model of care
      that could be taken to scale in our underdeveloped South African primary health
      care system. METHODS: Professional action research utilised a co-operative
      inquiry group that consisted of four nurses, one doctor and a qualitative
      researcher. The inquiry group implemented the protocol in two urban and three
      rural primary care facilities. Over a period of 14 months the group reflected on
      their experience, modified the protocol and developed recommendations on a
      practical but comprehensive model of care. RESULTS: The original protocol had to
      be adapted in terms of its expectations of the primary care providers, overly
      forensic orientation, lack of depth in terms of mental health, validity of the
      danger assessment and safety planning process, and need for ongoing empowerment
      and support. A three-tier model resulted: case finding and clinical care
      provision by primary care providers; psychological, social and legal assistance
      by 'IPV champions' followed by a group empowerment process; and then ongoing
      community-based support groups. CONCLUSION: The inquiry process led to a model of
      comprehensive and intersectoral care that is integrated at the facility level and
      which is now being piloted in the Western Cape, South Africa.

PMID- 23151249
TI  - Carotid sinus syndrome as the presenting symptom of cystadenolymphoma.
AB  - Carotid sinus syndrome is a serious manifestation of head and neck malignancy.
      The purpose of this study was to clarify the presence of carotid sinus syndrome
      in a patient with cystadenolymphoma. To our knowledge carotid sinus syndrome
      secondary to cystadenolymphoma has not been reported to date. A 45-year-old woman
      with one-week-old swelling in the left mandibular angle having disturbing
      symptoms of vertigo, consciousness and sinus arrest. Holter monitoring revealed
      several episodes of sinus arrest. Ultrasonography showed a well-defined space
      occupying lesion of about 31 mm in length and 17 mm in width located in the deep
      lobe of the left parotid gland. Computerized tomography (CT) showed a large mass
      extending into the carotid space and protruding into the parapharyngeal space.
      Parotidectomy was performed. Surgical removal of the tumor resulted in complete
      amelioration of symptoms and disappearance of electrocardiogram abnormalities.
      Here we report on a clinical case of carotid sinus syndrome associated with
      cystadenolymphoma. To our knowledge carotid sinus syndrome secondary to
      cystadenolymphoma has not been reported to date, and is made more remarkable as a
      possible differential diagnosis after clarification of all possible causes. Early
      diagnosis and immediate management can minimize complications.

PMID- 23151250
TI  - Stabilizing the pro-apoptotic BimBH3 helix (BimSAHB) does not necessarily enhance
      affinity or biological activity.
AB  - An attractive approach for developing therapeutic peptides is to enhance binding
      to their targets by stabilizing their alpha-helical conformation, for example,
      stabilized BimBH3 peptides (BimSAHB) designed to induce apoptosis. Unexpectedly,
      we found that such modified peptides have reduced affinity for their targets, the
      pro-survival Bcl-2 proteins. We attribute this loss in affinity to disruption of
      a network of stabilizing intramolecular interactions present in the bound state
      of the native peptide. Altering this network may compromise binding affinity, as
      in the case of the BimBH3 stapled peptide studied here. Moreover, cells exposed
      to these peptides do not readily undergo apoptosis, strongly indicating that
      BimSAHB is not inherently cell permeable.

PMID- 23151251
TI  - Editorial.

PMID- 23151252
TI  - Commentary on the clinical management of metabolic syndrome: why a healthy
      lifestyle is important.
AB  - Metabolic syndrome (MS) is associated with an increased risk of type 2 diabetes
      mellitus and cardiovascular diseases. There is no recognized method to manage MS.
      Many physicians treat the individual characteristics of MS (high blood pressure,
      high triglycerides, and so on) instead of the syndrome as a whole, placing
      particular emphasis on those components that are easily amenable to drug
      treatment. However, regular physical exercise and a healthy diet have been
      demonstrated to improve the health of a number of populations, but few studies
      have assessed their effects in patients with MS. A meta-analysis by Yamaoka and
      Tango in BMC Medicine found that a lifestyle change program (dietary counseling
      and encouragement to exercise) resulted in improvements in components of MS and
      in reducing the proportion of patients with MS. The effects may not be impressive
      in absolute terms, but the data should be interpreted with the heterogeneity of
      the included studies in mind. Because of the many adverse side effects of the
      drugs used to correct individual aspects of MS, this meta-analysis provides
      strong evidence that lifestyle changes must be the first-line approach to manage
      MS.See related article http://www.biomedcentral.com/1741-7015/10/138/abstract.

PMID- 23151253
TI  - Neutrophil gelatinase-associated lipocalin (NGAL) may play a protective role
      against rats ischemia/reperfusion renal injury via inhibiting tubular epithelial
      cell apoptosis.
AB  - We investigated the protective effect and mechanism of neutrophil gelatinase
      associated lipocalin (NGAL) on rats ischemia/reperfusion (I/R) renal injury.
      Eighteen Sprague-Dawley male rats were randomly divided into three groups.
      Control group (n = 6) suffered left unilateral nephrectomy, I/R + NS (normal
      saline) (n = 6) and I/R + NGAL (n = 6) group were subjected to 45 min right renal
      ischemia/24 h reperfusion after left unilateral nephrectomy. Serum creatinine
      (Scr) and blood urea nitrogen (Bun) were measured on automatic biochemistry
      analyzer; kidney sections were stained with hematoxylin-eosin; terminal dUTP nick
      labeling method was used to examine the apoptosis of tubular epithelial cells;
      Cleaved caspase-3 and Bax protein expression were detected by
      immunohistochemistry and Western Blot; real-time polymerase chain reaction was
      used to detect the expression of Bax mRNA. Rats with NGAL displayed an attenuated
      renal damage and a decreased number of tubular epithelial cell apoptosis compared
      to the I/R + NS group (Scr 63.400 +/- 11.908 vs. 121.857 +/- 17.151 MUmol/L, Bun
      14.840 +/- 2.868 vs. 28.557 +/- 6.434 mmol/L, apoptosis cell number 7.800 +/-
      1.924 vs. 15.400 +/- 3.049/high power field (HPF), p < 0.05), the values were
      lower in the control group (24.000 +/- 3.829 MUmol/L, 5.814 +/- 1.961 mmol/L,
      1.800 +/- 0.837/HPF, p < 0.05) compared to two groups above; NGAL-treated rats
      showed down-regulated Cleaved caspase-3 protein (0.284 +/- 0.066 vs. 0.409 +/-
      0.073, p < 0.05), Bax protein (0.346 +/- 0.055 vs. 0.443 +/- 0.041, p < 0.05),
      Bax mRNA (1.423 +/- 0.187 vs. 2.550 +/- 0.217, p < 0.05) compared to I/R + NS
      group, but the values were higher in both of the two groups than those in the
      control group (Cleaved caspase-3 protein 0.104 +/- 0.029, Bax protein 0.155 +/-
      0.027, Bax mRNA 1.000 +/- 0.000, p < 0.05). We supposed that exogenous NGAL can
      inhibit the activation of caspase-3, reduce the expression of Bax, and thus
      reduce renal tubular cell apoptosis and protect renal function in I/R injury
      rats.

PMID- 23151255
TI  - What do patients find helpful in psychotherapy? Implications for the therapeutic
      relationship in mental health nursing.
AB  - This study examined client perception of the therapeutic impact of two models of
      therapy delivered by mental health nurses and clinical psychologists respectively
      - psychodynamic interpersonal therapy (PIT) and cognitive behavioural therapy
      (CBT). A non-equivalent groups design was used in order to benchmark results
      against Llewelyn et al.: one group received PIT and the other received CBT. This
      design was utilized principally because the research was conducted across two
      practice settings where randomization was not feasible. We used two intact groups
      in practice research settings that received the therapies as reported in Llewelyn
      et al. Sixty-one clients receiving CBT or PIT in practice research settings
      completed a Helpful Aspects of Therapy form after each session in order to
      measure client perceptions of helpful and hindering events in therapy. Only two
      out of the 13 impacts were rated as significantly different. PIT clients reported
      higher levels of 'awareness' than CBT clients, whereas CBT clients reported
      higher levels of problem solution than PIT clients. The results replicate
      Llewelyn et al.'s findings in that clients experienced theoretically different
      models of therapy as broadly similar in their therapeutic impact. We argue that
      this provides some support for the influence of 'common' rather than 'specific'
      factors in psychotherapy effectiveness in mental health nursing.

PMID- 23151254
TI  - Quantitative assessment of gait and neurochemical correlation in a classical
      murine model of Parkinson's disease.
AB  - BACKGROUND: Gait deficits are important clinical symptoms of Parkinson's disease
      (PD). However, existing behavioral tests for the detection of motor impairments
      in rodents with systemic dopamine depletion only measure akinesia and dyskinesia,
      and data focusing on gait are scarce. We evaluated gait changes in the methyl-4
      phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced C57BL/6 murine model of PD by
      using a computer-assisted CatWalk system. Correlations of gait parameters with
      tyrosine hydroxylase (TH) protein levels in the substantia nigra (SN) were also
      investigated. RESULTS: The gait readouts, including the walking duration,
      variation of walking speed, step cycle, duty cycle, stance, initial dual stance,
      terminal dual stance, three- and four-point supports, and the base of support
      between hind limbs was noted to increase significantly one week after MPTP
      injection. In contrast, values of the stride length, cadence, swing speed, and
      diagonal dual support decreased substantially following MPTP treatment (p <
      0.05). All of these changes lasted for three weeks after the last MPTP
      administration. Except for the stance in the fore limbs and the swing speed in
      the hind limbs, the gait variability in the PD mice showed a closer correlation
      with the protein levels of TH in the SN than the walking distances in the
      conventional open field test. Coordination parameters of the regularity index and
      step pattern were not affected in mice treated with MPTP. CONCLUSION: Data of the
      study suggest that the computer-assisted CatWalk system can provide reliable and
      objective criteria to stratify gait changes arising from MPTP-induced bilateral
      lesions in C57/BL6 mice. The extent of gait changes was noted to correlate with
      the expression of the biomarker for dopaminergic neurons. This novel analytical
      method may hold promise in the study of disease progression and new drug
      screening in a murine PD model.

PMID- 23151257
TI  - Adsorption-desorption study of BSA conjugated silver nanoparticles (Ag/BSA NPs)
      on collagen immobilized substrates.
AB  - There has been a growing interest in the use of protein conjugated nanoparticles
      for applications in biomedical, sensing, and advanced imaging. The objective of
      this study was to understand the interaction of protein conjugated silver
      nanoparticles (Ag/BSA NPs) with biological substrate (collagen layer). The
      adsorption behavior of synthesized Ag/BSA NPs on collagen immobilized silanized
      surface was followed by UV-vis spectroscopy by initially studying the formation
      of collagen layer and subsequent adsorption of Ag/BSA NPs to the immobilized
      layer. Surface plasmon resonance (SPR) data provided the real time profile of
      adsorption of Ag/BSA NPs from solution onto collagen immobilized and control
      substrates as well as desorption of nanoparticles from the substrates. The
      retention of NPs to substrate is sensitive to chemistry of the underlying
      substrate and on the external environment. UV-vis and atomic absorption
      spectrometric analysis of Ag/BSA NPs desorption performed under different pH
      conditions showed more NPs retained at physiological pH than the acidic and basic
      conditions. Nanoparticles retention on collagen immobilized substrate at
      physiological pH could influence properties of biological interest such as
      circulation lifetime and biodistribution of nanoparticles in the body.

PMID- 23151256
TI  - APOA5 Q97X mutation identified through homozygosity mapping causes severe
      hypertriglyceridemia in a Chilean consanguineous family.
AB  - BACKGROUND: Severe hypertriglyceridemia (HTG) has been linked to defects in LPL,
      APOC2, APOA5, LMF1 and GBIHBP1 genes. However, a number of severe HTG cases are
      probably caused by as yet unidentified mutations. Very high triglyceride plasma
      levels (>112 mmol/L at diagnosis) were found in two sisters of a Chilean
      consanguineous family, which is strongly suggestive of a recessive highly
      penetrant mutation. The aim of this study was to determine the genetic locus
      responsible for the severe HTG in this family. METHODS: We carried out a genome
      wide linkage study with nearly 300,000 biallelic markers (Illumina Human CytoSNP
      12 panel). Using the homozygosity mapping strategy, we searched for chromosome
      regions with excess of homozygous genotypes in the affected cases compared to non
      affected relatives. RESULTS: A large homozygous segment was found in the long arm
      of chromosome 11, with more than 2,500 consecutive homozygous SNP shared by the
      proband with her affected sister, and containing the APOA5/A4/C3/A1 cluster.
      Direct sequencing of the APOA5 gene revealed a known homozygous nonsense Q97X
      mutation (p.Gln97Ter) found in both affected sisters but not in non-affected
      relatives nor in a sample of unrelated controls. CONCLUSION: The Q97X mutation of
      the APOA5 gene in homozygous status is responsible for the severe
      hypertriglyceridemia in this family. We have shown that homozygosity mapping
      correctly pinpointed the genomic region containing the gene responsible for
      severe hypertriglyceridemia in this consanguineous Chilean family.

PMID- 23151258
TI  - Probing the nature of chemical bonding in uranyl(VI) complexes with quantum
      chemical methods.
AB  - To assess the nature of chemical bonds in uranyl(VI) complexes with Lewis base
      ligands, such as F(-), Cl(-), OH(-), CO(3)(2-), and O(2)(2-), we have used
      quantum chemical observables, such as the bond distances, the internal
      symmetric/asymmetric uranyl stretch frequencies, and the electron density with
      its topology analyzed using the quantum theory of atoms-in-molecules. This
      analysis confirms that complex formation induces a weakening of the uranium-axial
      oxygen bond, reflected by the longer U-O(yl) bond distance and reduced uranyl
      stretching frequencies. The strength of the ligand-induced effect increases in
      the order H(2)O < Cl(-) < F(-) < OH(-) < CO(3)(2-) < O(2)(2-). In-depth analysis
      reveals that the trend across the series does not always reflect an increasing
      covalent character of the uranyl-ligand bond. By using a point-charge model for
      the uranyl tetra-fluoride and tetra-chloride complexes, we show that a
      significant part of the uranyl bond destabilization arises from purely
      electrostatic interactions, the remaining part corresponding either to charge
      transfer from the negatively charged ligands to the uranyl unit or a covalent
      interaction. The charge-transfer and the covalent interaction are qualitatively
      different due to the absence of a charge build up in the uranyl-halide bond
      region in the latter case. In all the charged complexes, the uranyl-ligand bond
      is best described as an ionic interaction. However, there are covalent
      contributions in the very stable peroxide complex and, to some extent, also in
      the carbonate complex. This study demonstrates that it is possible to describe
      the nature of chemical bond by observables rather than by ad hoc quantities such
      as atomic populations or molecular orbitals.

PMID- 23151259
TI  - Characterization of fibrinogen glycosylation and its importance for serum/plasma
      N-glycome analysis.
AB  - The majority of proteins present in human serum/plasma are glycoproteins,
      validating this fluid as an ideal starting material for N-glycan analysis and
      discovery of potential biomarkers. The glycoprotein content for both serum and
      plasma is very similar, except for proteins removed in the coagulation process,
      including fibrinogen. Our aim was to characterize fibrinogen glycosylation in
      order to determine its contribution to differences between serum and plasma N
      glycomes. N-Glycans from human fibrinogen were released, labeled, and analyzed by
      HILIC-HPLC and MS. Structural characterization of fibrinogen subunits revealed
      that the alpha chain was not N-glycosylated, whereas beta and gamma contained
      identical oligosaccharide structures, mainly biantennary digalactosylated
      monosialylated structures (A2G2S1) and biantennary digalactosylated disialylated
      structures (A2G2S2). Blood was collected from five healthy volunteers into four
      testing tubes: silicone-coated glass for serum and EDTA, Na-heparin, and Li
      heparin glass tubes for plasma. N-Glycans were analyzed using the high-throughput
      HILIC-HPLC method. N-Glycan profiles from serum and plasma samples differed
      largely in glycans identified in fibrinogen, suggesting that this glycoprotein
      represents a major factor distinguishing these body fluids. This result
      emphasizes the important of consistent body fluid collection practices in
      biomarker discovery studies.

PMID- 23151260
TI  - Blink rate in ALS.

PMID- 23151261
TI  - Parental age and the risk of amyotrophic lateral sclerosis.
AB  - Sporadic ALS is a multifactorial disease for which there are probably multiple
      genetic risk factors. An association with increased parental age might suggest
      there is a role for specific (epi)genetic changes. Previous studies have shown
      conflicting results on the association between parental age and the risk of ALS.
      A large, population based study might help in the search for specific
      (epi)genetic risk factors. We performed a population based, case-control study in
      the Netherlands. Date of birth of both mother and father was retrieved from the
      National Register. Multivariate logistic regression analysis was performed in 769
      patients with sporadic ALS, 49 patients with a hexanucleotide repeat expansion in
      C9orf72, and 1929 age-, gender- and geographically-matched controls. Multivariate
      analyses showed no difference in either paternal or maternal age at delivery
      (adjusted for age of subject, age of other parent at delivery, and level of
      education) in patients with sporadic ALS, nor in patients with a hexanucleotide
      repeat expansion in C9orf72 compared to controls. In conclusion, parental age was
      not associated with an increased risk of ALS in our study. (Epi)genetic
      alterations that are associated with increased parental age are not, therefore,
      likely to contribute to the aetiology of sporadic ALS.

PMID- 23151262
TI  - Nucleophilic substitution reaction at the nitrogen of arylsulfonamides with
      phosphide anion.
AB  - A novel nucleophilic substitution reaction at the nitrogen of arylsulfonamides by
      means of phosphide anions has been described. This reaction allows for the
      efficient transformation of arylsulfonamides into synthetically valuable
      phosphamides, amines, and a variety of protected amines.

PMID- 23151264
TI  - Synthesis and biological activity of nitric oxide-releasing derivatives of
      ferulic acid as potential agents for the treatment of chronic kidney diseases.
AB  - In order to search for novel potential agents for the treatment of chronic kidney
      diseases (CKD), nitric oxide (NO)-releasing derivatives (5a-c) of ferulic acid
      were synthesized and characterized by MS, 1H NMR, and elementary analysis. They
      showed different NO-releasing rate in the absence or presence of L-cysteine in
      vitro. In the adenine induced CKD rats, these compounds revealed reno-protective
      effect via lowering blood urea nitrogen (BUN), creatinine (Cr) in serum and
      malondialdehyde (MDA) in kidney, increasing NO and superoxide dismutase (SOD)
      level in kidney. Among them, 3-methoxy-4-(nitrooxy)ethoxy cinnamic acid (5a) was
      confirmed to have a higher NO-releasing rate in vitro and better effect in
      ameliorating adenine-induced kidney damage in rats. 

PMID- 23151263
TI  - Prevalence of HIV among MSM in Europe: comparison of self-reported diagnoses from
      a large scale internet survey and existing national estimates.
AB  - BACKGROUND: Country level comparisons of HIV prevalence among men having sex with
      men (MSM) is challenging for a variety of reasons, including differences in the
      definition and measurement of the denominator group, recruitment strategies and
      the HIV detection methods. To assess their comparability, self-reported data on
      HIV diagnoses in a 2010 pan-European MSM internet survey (EMIS) were compared
      with pre-existing estimates of HIV prevalence in MSM from a variety of European
      countries. METHODS: The first pan-European survey of MSM recruited more than
      180,000 men from 38 countries across Europe and included questions on the year
      and result of last HIV test. HIV prevalence as measured in EMIS was compared with
      national estimates of HIV prevalence based on studies using biological
      measurements or modelling approaches to explore the degree of agreement between
      different methods. Existing estimates were taken from Dublin Declaration
      Monitoring Reports or UNAIDS country fact sheets, and were verified by contacting
      the nominated contact points for HIV surveillance in EU/EEA countries. RESULTS:
      The EMIS self-reported measurements of HIV prevalence were strongly correlated
      with existing estimates based on biological measurement and modelling studies
      using surveillance data (R(2)=0.70 resp. 0.72). In most countries HIV positive
      MSM appeared disproportionately likely to participate in EMIS, and prevalences as
      measured in EMIS are approximately twice the estimates based on existing
      estimates. CONCLUSIONS: Comparison of diagnosed HIV prevalence as measured in
      EMIS with pre-existing estimates based on biological measurements using varied
      sampling frames (e.g. Respondent Driven Sampling, Time and Location Sampling)
      demonstrates a high correlation and suggests similar selection biases from both
      types of studies. For comparison with modelled estimates the self-selection bias
      of the Internet survey with increased participation of men diagnosed with HIV has
      to be taken into account. For most countries self-reported EMIS prevalence is
      higher than measured prevalence, which is likely due to a combination of
      different time points of measurement, measurement errors for small sample sizes,
      different sampling methods, and an indicator-inherent overestimate of prevalence
      among the untested fraction of MSM.

PMID- 23151265
TI  - Synthesis of benzophenonehydrazone Schiff bases and their in vitro antiglycating
      activities.
AB  - Benzophenonehydrazone Schiff bases 1-25 were synthesized and their in vitro
      antiglycation potential has been studied. Out of twenty-five compounds, thirteen
      showed varying degrees of antiglycation activity with IC50 values ranging between
      25.7 - 305 MUM, if compared with the standard rutin (IC50 = 70.5 +/- 0.50 MUM).
      Compounds 21 (2,3- dihydroxybenzaldehyde N-(diphenylmethylene)hydrazine) IC50 =
      25.7 +/- 0.003 MUM, 14 (diphenylmethanone N-[1-(2,4- dihydroxy-5
      nitrophenyl)ethylidene]hydrazine) IC50 = 36.6 +/- 0.004 MUM, 6 (3,4
      dihydroxybenzaldehyde N- (diphenylmethylene)hydrazine) IC50 = 49.5 +/- 0.001 MUM,
      13 (diphenylmethanone N-[1-(2,5-dihydroxyphenyl)ethylidene] hydrazine) IC50 =
      52.6 +/- 0.023 MUM, and 15 (diphenylmethanone N-[1-(3,4
      dihydroxyphenyl)ethylidene]hydrazine) IC50 = 57 +/- 0.002 MUM, showed showed much
      better antiglycation potential superior to the standard rutin. The compounds 7
      (2,5- dihydroxybenzaldehyde N-(diphenylmethylene)hydrazine) IC50 = 66 +/- 0.002
      MUM, and 25 (diphenylmethanone N-[1-(2,5- dihydroxyphenyl)propylidene] hydrazine)
      IC50 = 67.9 +/- 0.001 MUM showed compareably good antiglycation activity to
      standard rutin. All compounds were characterized by spectroscopic techniques and
      gave satisfactory elemental analysis.

PMID- 23151266
TI  - In-silico analysis of chromone containing sulfonamide derivatives as human
      carbonic anhydrase inhibitors.
AB  - Computational tools of analysis were used on a set of synthetic chromone
      containing sulfonamide derivatives for evaluation of their enzyme inhibitory
      activity against Carbonic Anhydrase (CA) isozymes. GOLD docking software was
      utilized to dock the compounds against two human Carbonic Anhydrase (hCA)
      proteins; hCAII and hCA-IX. Differences in conformation and orientation of
      molecules within hCA-II and hCA-IX binding pockets were studied in detail which
      revealed that compounds with fluorine at R1 position and phenyl sulfonamide
      substituent at para position served as potent inhibitors against both proteins
      due to anomalous chemistry of fluorine atom. It was also noticed that the
      activity was decreased when sulfonamide moiety was shifted from para to meta
      position since it dragged the interacting specie of compounds away from Zn metal.
      Similarly, when substituents were replaced by F > Br > C2H5 > H, the activity
      declined due to the electronegativity effect. Binding interaction results against
      CA-IX seemed to be better than CA-II due to large binding cavity, predicting the
      more potent inhibitory activity against hCA-IX.

PMID- 23151267
TI  - Mycobacterium bovis infection at the interface between domestic and wild animals
      in Zambia.
AB  - BACKGROUND: In Zambia, the presence of bovine tuberculosis in both wild and
      domestic animals has long been acknowledged and mutual transmission between them
      has been predicted without any direct evidence. Elucidation of the circulating
      Mycobacterium bovis strains at wild and domestic animals interphase area in
      Zambia, where bovine tuberculosis was diagnosed in wildlife seemed to be
      important. RESULTS: A PCR identified 15 and 37 M. bovis isolates from lechwe and
      cattle, respectively. Spoligotype analysis revealed that M. bovis strains from
      lechwe and cattle in Kafue basin clustered into a major node SB0120, where
      isolates outside the Kafue basin clustered into different nodes of SB0131 and
      SB0948. The comparatively higher variety of strains in cattle compared to lechwe
      elucidated by Mycobacterial Interspersed Repetitive Units-Variable Number Tandem
      Repeats analyses are consistent with cattle being the probable source of M. bovis
      in wild and domestic animals interphase area in Zambia. CONCLUSIONS: These
      results provide strong evidence of M. bovis strains transfer between cattle and
      lechwe, with the latter having developed into a sylvatic reservoir host.

PMID- 23151268
TI  - Newly proposed therapy-related myelodysplastic syndrome prognostic score predicts
      significant differences in overall survival and leukemia-free survival in
      patients treated with azacitidine.

PMID- 23151269
TI  - Hepato-protective effects of alpha lipoic acid besides its role in preventing
      fatty liver disease.

PMID- 23151270
TI  - Decreased proportions of indoor feeding and endophily in Anopheles gambiae s.l.
      populations following the indoor residual spraying and insecticide-treated net
      interventions in Benin (West Africa).
AB  - BACKGROUND: In many parts of Africa as in Benin, the main strategies of vector
      control are based on the scaling-up of Long Lasting Insecticide Treated Nets
      (LLITNs) and indoor residual spraying (IRS). The need to understand the
      biological implications of IRS in large scale and full coverage of LLITNs is
      paramount. It is in this context that the present study was conducted. It aims to
      evaluate the effect of a large scale IRS using a non-pyrethroid insecticide and
      full coverage of deltamethrin treated nets on the behavior of An. gambiae s.l. in
      the intervention areas compared to untreated areas used as controls. METHODS:
      Mosquitoes were collected using human landing catches, pyrethrum spray catches
      and window exit traps to assess reduction of entry rate, endophily rate,
      endophagy rate and overall mortality rate in natural populations of An. gambiae
      s.l. before IRS and LLITNs intervention (2007) and after in 2008 and 2010.
      RESULTS: In the IRS arm, endophily rate was 67.13% before intervention and 4.5%
      after intervention, whereas in the control arm it was stable at 51.67% (P > 0
      .05). In the LLITN arm endophily rates also decreased after intervention. After
      the IRS, no gravid mosquitoes were collected from all treated localities, but
      LLITN performance was not that spectacular. The proportion of mosquitoes biting
      indoors in the IRS arm decreased from 67.09% before intervention to 42.85% after
      intervention, compared to a low but significant decrease (71.31% to 57. 46%) in
      the LLITN arm.The use of vector control tools and behavior of the host would be
      the main factors that modify the behavior of taking a human blood meal observed
      on An. gambiae s.l. inside human dwellings. CONCLUSION: The impact on the
      behavior of An. gambiae s.l. observed with the bendiocarb used in IRS was highly
      effective compared with the free distribution of LLITNs in terms of mortality and
      the decrease of proportions of indoor feeding. Despite this efficacy, there is a
      need for complementary tools and research of alternative strategy oriented on
      effective health education, and the use of powerful tools such as IRS, LLITNs,
      larviciding and repellents.

PMID- 23151271
TI  - Interphase chromosome positioning in in vitro porcine cells and ex vivo porcine
      tissues.
AB  - BACKGROUND: In interphase nuclei of a wide range of species chromosomes are
      organised into their own specific locations termed territories. These chromosome
      territories are non-randomly positioned in nuclei which is believed to be related
      to a spatial aspect of regulatory control over gene expression. In this study we
      have adopted the pig as a model in which to study interphase chromosome
      positioning and follows on from other studies from our group of using pig cells
      and tissues to study interphase genome re-positioning during differentiation. The
      pig is an important model organism both economically and as a closely related
      species to study human disease models. This is why great efforts have been made
      to accomplish the full genome sequence in the last decade. RESULTS: This study
      has positioned most of the porcine chromosomes in in vitro cultured adult and
      embryonic fibroblasts, early passage stromal derived mesenchymal stem cells and
      lymphocytes. The study is further expanded to position four chromosomes in ex
      vivo tissue derived from pig kidney, lung and brain. CONCLUSIONS: It was
      concluded that porcine chromosomes are also non-randomly positioned within
      interphase nuclei with few major differences in chromosome position in interphase
      nuclei between different cell and tissue types. There were also no differences
      between preferred nuclear location of chromosomes in in vitro cultured cells as
      compared to cells in tissue sections. Using a number of analyses to ascertain by
      what criteria porcine chromosomes were positioned in interphase nuclei; we found
      a correlation with DNA content.

PMID- 23151272
TI  - Estimation of the solubility parameters of model plant surfaces and
      agrochemicals: a valuable tool for understanding plant surface interactions.
AB  - BACKGROUND: Most aerial plant parts are covered with a hydrophobic lipid-rich
      cuticle, which is the interface between the plant organs and the surrounding
      environment. Plant surfaces may have a high degree of hydrophobicity because of
      the combined effects of surface chemistry and roughness. The physical and
      chemical complexity of the plant cuticle limits the development of models that
      explain its internal structure and interactions with surface-applied
      agrochemicals. In this article we introduce a thermodynamic method for estimating
      the solubilities of model plant surface constituents and relating them to the
      effects of agrochemicals. RESULTS: Following the van Krevelen and Hoftyzer
      method, we calculated the solubility parameters of three model plant species and
      eight compounds that differ in hydrophobicity and polarity. In addition, intact
      tissues were examined by scanning electron microscopy and the surface free
      energy, polarity, solubility parameter and work of adhesion of each were
      calculated from contact angle measurements of three liquids with different
      polarities. By comparing the affinities between plant surface constituents and
      agrochemicals derived from (a) theoretical calculations and (b) contact angle
      measurements we were able to distinguish the physical effect of surface roughness
      from the effect of the chemical nature of the epicuticular waxes. A solubility
      parameter model for plant surfaces is proposed on the basis of an increasing
      gradient from the cuticular surface towards the underlying cell wall.
      CONCLUSIONS: The procedure enabled us to predict the interactions among
      agrochemicals, plant surfaces, and cuticular and cell wall components, and
      promises to be a useful tool for improving our understanding of biological
      surface interactions.

PMID- 23151273
TI  - Influence of gamma-radiation on the structure and function of soybean trypsin
      inhibitor.
AB  - Soybean trypsin inhibitor (STI) is a known antinutrient and food allergen present
      in soybean. gamma-Radiation has the potential to inactivate the TI protein.
      However, a systematic study on the influence of different moisture levels during
      gamma radiation on structure and function of the molecule has not been reported.
      Pure STI was irradiated up to 200 kGy, in dry state, with 50% moisture and in
      aqueous solution. The radiation damage in molecular structure was assessed using,
      SDS-PAGE, size exclusion chromatography, fluorescence measurement, and circular
      dichroism, while functional damage was assessed by the TI assay. In aqueous
      solution, both the structure and function of TI were almost destroyed at the 10
      kGy dose. While with 50% moisture and in dry state, the loss in functional and
      structural attributes was discernible only at 30 and 100 kGy, respectively. The
      TI activity was found to be unaffected in dry and soaked seeds of soybean as well
      as other legumes up to irradiation doses of 100 and 50 kGy, respectively.

PMID- 23151274
TI  - Sepsis in transit: from clinical to molecular classification.
AB  - In the previous issue of Critical Care, Maslove and colleagues studied
      circulating neutrophil transcriptional expression to discover and validate a
      molecular subclassification of adult patients with sepsis. The authors divided
      patients into small derivation (n = 55) and validation (n = 71) cohorts. Their
      complex methodology included partitioning around medoid and hierarchical
      clustering methods to define two transcriptionally distinct subtypes of sepsis.
      Pathway analysis found that chemokine and cytokine pathways as well as Toll-like
      receptor signaling were enhanced. Investigation of specific drug target genes
      relevant to sepsis found significantly different expression levels between the
      two molecular subtypes. Interestingly, most patient characteristics did not
      differ between groups, except for an increase in the proportion of severe sepsis
      in molecular subtype 1. Possible confounders of this study were the small sample
      size, population stratification, and lack of information regarding drug
      interventions, all of which support the need for more studies with larger cohorts
      that include transcriptional profiles. This thought-provoking hypothesis
      generating study could lead to a new neutrophil expression-based molecular
      classification of adult sepsis. 

PMID- 23151276
TI  - Effect of a prostaglandin F2alpha analogue on the cyclic corpus luteum during its
      refractory period in cows.
AB  - BACKGROUND: The goal of this study was to examine the response of the cyclic
      corpus luteum of cows to the administration of a prostaglandin F2alpha analogue
      (PGF) during the transition of refractoriness to responsiveness by investigating
      ultrasonographic changes in the corpus luteum and changes in plasma progesterone
      concentration in cows following the administration of PGF 3 and 5 days after
      ovulation. RESULTS: All cows that responded to PGF given on day 5 ovulated on day
      9. In the cows that did not respond on day 5, the luteal cross-sectional area
      stagnated after treatment, whereas the plasma progesterone concentration
      continued to increase. In the cows that received PGF on day 3 of the oestrous
      cycle, the luteal cross-sectional area and the plasma progesterone concentration
      continued to increase. CONCLUSIONS: The results of this study suggest that the
      transition of the bovine corpus luteum from refractoriness to responsiveness to
      PGF occurs during day 5 of the oestrous cycle because in 5 of 8 cows given PGF on
      day 5, early luteal regression was evident during the examination 24 hours after
      PGF administration.

PMID- 23151275
TI  - Relationships between serum MCP-1 and subclinical kidney disease: African
      American-Diabetes Heart Study.
AB  - AB BACKGROUND: Monocyte chemoattractant protein-1 (MCP-1) plays important roles
      in kidney disease susceptibility and atherogenesis in experimental models.
      Relationships between serum MCP-1 concentration and early nephropathy and
      subclinical cardiovascular disease (CVD) were assessed in African Americans (AAs)
      with type 2 diabetes (T2D). METHODS: Serum MCP-1 concentration, urine
      albumin:creatinine ratio (ACR), estimated glomerular filtration rate (eGFR), and
      atherosclerotic calcified plaque (CP) in the coronary and carotid arteries and
      infrarenal aorta were measured in 479 unrelated AAs with T2D. Generalized linear
      models were fitted to test for associations between MCP-1 and urine ACR, eGFR,
      and CP. RESULTS: Participants were 57% female, with mean +/- SD (median) age 55.6
      +/- 9.5 (55.0) years, diabetes duration 10.3 +/- 8.2 (8.0) years, urine ACR 149.7
      +/- 566.7 (14.0) mg/g, CKD-EPI eGFR 92.4 +/- 23.3 (92.0) ml/min/1.73 m(2), MCP-1
      262.9 +/- 239.1 (224.4) pg/ml, coronary artery CP 280.1 +/- 633.8 (13.5), carotid
      artery CP 47.1 +/- 132.9 (0), and aorta CP 1616.0 +/- 2864.0 (319.0). Adjusting
      for age, sex, smoking, HbA1c, BMI, and LDL, serum MCP-1 was positively associated
      with albuminuria (parameter estimate 0.0021, P=0.04) and negatively associated
      with eGFR (parameter estimate -0.0003, P=0.001). MCP-1 remained associated with
      eGFR after adjustment for urine ACR. MCP-1 levels did not correlate with the
      extent of CP in any vascular bed, HbA1c or diabetes duration, but were positively
      associated with BMI. No interaction between BMI and MCP-1 was detected on
      nephropathy outcomes. CONCLUSIONS: Serum MCP-1 levels are associated with eGFR
      and albuminuria in AAs with T2D. MCP-1 was not associated with subclinical CVD in
      this population. Inflammation appears to play important roles in development
      and/or progression of kidney disease in AAs.

PMID- 23151277
TI  - Left atrial endocarditis as a rare complication of mitral valve endocarditis: a
      clinical case.
AB  - BACKGROUND: Infective Endocarditis (IE) is considered as a multifaceted problem
      in every aspect from etiology and presentation to diagnosis and management. Early
      recognition of this disease and especially its complications, remain a critical
      task for the cardiologist. Atrial endocarditis is a rare and sometimes
      unrecognized complication of mitral valve endocarditis. CASE PRESENTATION: We
      present a 48 year-old male patient who was admitted to our clinic because of
      recent onset of malaise, fever, jaundice and peripheral edema. Important physical
      findings were peripheral stigmata of IE in addition to holosystolic murmur over
      the left sternal border. Transthoracic and transesophageal echocardiophy revealed
      a severe eccentric MR due to a flailed posterior mitral valve caused by IE. The
      presence of atrial septal endocarditis caused by jet streaming was also observed.
      Blood culture was positive for streptococcus oralis and antibiotic therapy was
      immediately initiated. Considering the large burden of infective tissue, the
      patient was planned for an early surgical intervention. A minimally invasive
      resection of the atrial mass, direct closure of the defect, resection of the
      diseased portions of mitral leaflets and implantation of a biological mitral
      valve prosthesis was performed. Intra-operative and histological findings
      confirmed provisional diagnosis by echocardiography. CONCLUSIONS: Together with
      comprehensive echocardiographic evaluation, attention should be placed on mural
      vegetations and excluded among all cases of mitral valve endocarditis,
      particularly those with severe eccentric regurgitant jets.

PMID- 23151278
TI  - Competition of hydrophobic steroids with sodium dodecyl sulfate,
      dodecyltrimethylammonium bromide, or dodecyl beta-D-maltoside for the
      dodecane/water interface.
AB  - The surface tension lowering abilities of insoluble steroids, progesterone and
      testosterone, were examined at the dodecane/water interface in the presence and
      absence of surfactants, sodium dodecyl sulfate, dodecyltrimethylammonium bromide,
      and dodecyl maltoside. In the absence of these surfactants, the steroids
      significantly lowered the interfacial tension while exhibiting no activity at the
      air/water and air/dodecane surfaces. Further, in mixtures of surfactants and
      steroids, significant enhancement of interfacial tension lowering was observed.
      At a sufficiently high concentration of surfactant, no further lowering of
      tension was observed in the presence of the steroids. The synergistic effects on
      interfacial tension of steroids and surfactants were characterized by the free
      energy of transfer to the interface of each solute based on a two-dimensional
      solution equation of state. Assuming no significant interaction between the
      steroids and the surfactants in the interface, predictions of interfacial
      tensions were made based on the calculated free energies of transfer and
      interfacial area occupied. Good agreement was found between the predicted values
      and experimental values for interfacial tension. The results of these studies
      show that progesterone and testosterone, molecules not normally thought of as
      surface active, exhibit significant interfacial activity and can successfully
      compete with surfactants for the dodecane/water interface.

PMID- 23151279
TI  - Repackaging cigarettes--will the courts thwart the FDA?

PMID- 23151280
TI  - Facing uncertainty--dispatch from Beth Israel Medical Center, Manhattan.

PMID- 23151281
TI  - The storm and the aftermath.

PMID- 23151282
TI  - Seeing in the dark.

PMID- 23151283
TI  - Palladium catalyzed one-pot sequential Suzuki cross-coupling-direct C-H
      functionalization of imidazo[1,2-a]pyrazines.
AB  - An efficient "one-pot" selective functionalization at C3/C6 of imidazo[1,2
      a]pyrazines has been developed via a palladium-catalyzed sequential Suzuki
      Miyaura cross-coupling/direct C-H arylation, vinylation, and benzylation. The
      procedure remains effective in the presence of a methyl thioether group at C8,
      which may in turn be successfully engaged in a cross-coupling method to afford
      3,6,8-trisubstituted imidazo[1,2-a]pyrazines. This work paves the way for the
      design of biologically relevant compounds in an imidazo[1,2-a]pyrazine series.

PMID- 23151284
TI  - The challenges of health care reform for hospital social work in the United
      States.
AB  - This article examines the potential impact of the Patient Protection and
      Affordable Care Act (ACA) of 2010 on the practice of hospital social work in the
      United States and its implications for social work education and training. It
      briefly traces the history of hospital social work, outlines some contemporary
      issues in the health care field, particularly those that create persistent health
      disparities, summarizes the major provisions of the Act that have implications
      for social work practice, and discusses how social workers in hospital settings
      might respond effectively to the changes produced by the legislation.

PMID- 23151285
TI  - Shared decision making in health care settings: a role for social work.
AB  - Shared decision making (SDM) is a process integral to social work practice, one
      where the provider/professional and the consumer/patient discuss treatment
      alternatives based on patient values and life circumstances and make a shared
      decision about whether and how to proceed with treatment. Evidence-based medicine
      suggests that for many health conditions, having the choice of several effective
      treatment options is not uncommon. In these cases treatment should be based on
      what is best for the individual, since many factors influence an individual's
      treatment preference, including the psychological, social, cultural, and
      spiritual history she/he brings to the medical encounter; a history that has long
      been ignored in somatic health care. This article develops the argument that
      medical social workers possess the professional knowledge and skill base to
      provide decisional coaching, and implementing SDM in primary care settings. Of
      particular importance are the values that guide professional social work
      practice, including client self-determination, which is the basis of SDM, and the
      ability to maintain neutrality.

PMID- 23151286
TI  - To live close to a person with cancer--experiences of family caregivers.
AB  - The purpose of this study was to obtain a deeper understanding of the experiences
      of Family Caregivers (FC) living close to a patient with cancer. This article
      reports on the findings from individual interviews with 15 FCs of patients with
      cancer. The interview transcripts were analyzed using qualitative hermeneutic
      analysis. This study revealed that living close to a cancer patient over the
      course of his or her illness affected many aspects of FCs lives in significant
      ways. Their experiences can be summarized with two major themes: (1) living in an
      ever changing life world and (2) balancing between conflicting interests and
      dilemmas. This study contributed to deeper insights into FC's experiences than
      previously reported in the literature.

PMID- 23151287
TI  - Epilepsy postings on YouTube: exercising individuals' and organizations' right to
      appear.
AB  - Philosopher Hannah Arendt maintains that everyone has the right to appear in
      public as an embodied, singular individual. Because of the stigma attached to
      epilepsy, many with this condition are denied this right. Using grounded theory
      techniques, the author analyzes uploads of epilepsy on YouTube. The author argues
      that personal uploads on YouTube are the only mass media examples in which those
      with epilepsy can exercise their right to appear without the interpretation of
      intermediaries. Emerging themes relating to "the right to appear" allow social
      workers to deepen understanding of this and other devastating, often invisible
      and sometimes life-threatening illnesses.

PMID- 23151293
TI  - Effect of periodontal therapy on prevention of gastric Helicobacter pylori
      recurrence: a systematic review and meta-analysis.
AB  - AIM: The aim of this review is to assess the effect of dental plaque control and
      periodontal therapy on prevention of gastric Helicobacter pylori (H. pylori)
      recurrence. MATERIALS AND METHODS: We conducted searches of electronic databases,
      and included controlled trials comparing periodontal treatment and eradication
      therapy of H. pylori with eradication therapy alone for prevention of recurrence
      of gastric H. pylori. We used the absence of recurrence of gastric H. pylori
      after the first 3 months as an outcome measure to determine relative risk of
      persistence of gastric H. pylori. We estimated the degree of heterogeneity among
      trial results using Q and I(2)  statistics. RESULTS: Three trials including 298
      patients were eligible according to our inclusion criteria. As significant
      heterogeneity was indicated by the Q statistics (p = 0.04) and I(2)  (69%), we
      used a random-effects model to combine the data. Compared with eradication
      therapy alone, the adjunction of periodontal therapy significantly reduced the
      relative risk of persistence of gastric H. pylori by 63% (0.37 [95% CI 0.21
      0.64], p = 0.0004) in patients with gastric diseases. CONCLUSIONS: The adjunction
      of periodontal treatment to eradication therapy appears to reduce gastric H.
      pylori recurrence compared with eradication therapy alone among patients with
      gastric diseases associated with H. pylori. The results of this meta-analysis
      should be taken with caution because of the limitations in the primary data.

PMID- 23151294
TI  - RCT comparing implants with turned and anodically oxidized surfaces: a pilot
      study, a 3-year follow-up.
AB  - AIM: This 3-year prospective randomized controlled trial compared the clinical,
      microbiological and biochemical outcome of minimally (Turned, Tur) and moderately
      rough (TiUnite((r)) , TiU) implant surfaces in a split-mouth design. MATERIAL AND
      METHODS: The study population included 14 subjects: nine fully edentulous and
      five partially edentulous subjects with a history of periodontitis. Implants (n =
      78, 39 Tur and 39 TiU) were installed randomly in each patient. Peri-implant
      clinical parameters and intra-oral radiographs were recorded after 3 years of
      loading. Subgingival plaque and peri-implant crevicular fluid samples were
      collected and analysed using culture and quantitative polymerase chain reaction
      for the biofilm, and enzyme-linked immunosorbent assay for the concentration of
      osteoprotegerin and receptor activator of nuclear factor kappa-B ligand,
      respectively. RESULTS: No statistically significant differences in clinical,
      microbiological and biochemical parameters could be observed when comparing the
      Tur and TiU implant surfaces. CONCLUSION: After 3 years of loading, in
      periodontitis susceptible patients, the moderately rough, TiU implants
      demonstrated a similar clinical outcome compared with the smoother, turned
      implants. Longer follow-up and studies using different implant types are needed
      to confirm the statement that minimally and moderately rough implant surfaces
      perform similar, both from a clinical and from a microbiological point of view.

PMID- 23151295
TI  - The incidence of peri-implantitis for two different implant systems over a period
      of thirteen years.
AB  - OBJECTIVES: To study the incidence of peri-implantitis over 13 years between two
      types of dental implants. MATERIALS AND METHODS: Peri-implantitis incidence was
      defined as bone loss >= 1.0 mm after 1 year, and with BOP or suppuration.
      RESULTS: Nineteen subjects with TioBlast AstraTech(TM)  (AT) and 22 subjects with
      machine-etched Branemark Nobel Biocare((r))  (NB) implants were studied. The
      incidences of peri-implantitis between years 1 and 7 and between years 7 and 13
      were 26.2% and 7.1% for AT implants, and 30.4% and 11.5% for NB implants (NS). A
      history of periodontitis was a risk for future incidence of peri-implantitis
      (Likelihood ratio: 4.1, 95% CI: 2.0, 8.4, p < 0.001). Subjects with a history of
      systemic disease had a higher incidence of peri-implantitis (p < 0.05).
      CONCLUSIONS: No difference in the incidence of peri-implantitis over a period of
      13 years as an effect implant surface and design was found. Bone loss during the
      first 7 years after implant installation was greater than thereafter.
      Microbiological information at year 7 did not predict incidence of peri
      implantitis at year 13. Subjects with a previous history of periodontitis and
      with systemic disease were at higher risk for future incidence of peri
      implantitis.

PMID- 23151296
TI  - Efficient induction of pluripotent stem cells from menstrual blood.
AB  - The technology to reprogram human somatic cells back to pluripotency allows the
      production of patient-specific induced pluripotent stem cells (iPSCs) and holds a
      great promise for regenerative medicine. Choosing the most suitable cell type for
      induction and reducing the risk of viral transgene activation, especially
      oncogene activation, are important for iPSC research. To date, human dermal
      fibroblasts (HDFs) are the most frequent cell source used for iPSC generation,
      but they have several limitations. An invasive skin biopsy must be performed to
      obtain HDFs, and HDFs must be cultured for a prolonged period before they can be
      used for experiments. Thus, in an effort to develop a suitable source for iPSC
      studies to avoid the limitations mentioned above, we have here identified stromal
      cells derived from menstrual blood (MenSCs) as suitable candidates. In the
      present study, we found that MenSCs can be reprogrammed to pluripotent status by
      doxycycline-inducible lentiviral transduction of OCT4, SOX2, and KLF4.
      Additionally, we found that MenSCs have a significantly higher reprogramming
      efficiency than HDFs. The combination of OCT4 and SOX2 is sufficient to reprogram
      MenSCs into iPSCs without the use of c-MYC or KLF4. The resulting MenSC-iPSCs
      showed the same characteristics as human embryonic stem cells with regard to
      morphology, pluripotent markers, gene expression, and the epigenetic status of
      pluripotent-cell-specific genes. These cells were able to differentiate into
      various cell types of all 3 germ layers both in vitro and in vivo. Therefore,
      MenSCs may be a preferred candidate for generation of iPSCs.

PMID- 23151298
TI  - Turn-on luminescent sensing of metal cations via quencher displacement: rational
      design of a highly selective chemosensor for chromium(III).
AB  - A highly selective luminescent chemosensor for Cr(3+) in aqueous solution was
      assembled by a low-selectivity luminogenic receptor with Cu(2+) as a metal
      quencher. Three tetranitrogen chelating sites were integrated into the
      multichannel receptor with a tris(1,10-phenanthroline)ruthenium(II) luminophore
      at the core. This receptor (2) exhibits chelating affinity for many transition
      metal cations, among which Cu(2+) efficiently quenches the emission. The further
      addition of Cr(3+) into the Cu(2+)-titrated solution of 2 results in a metal
      exchange reaction and a sensitive turn-on luminescence response highly selective
      over other metal cations. The quencher displacement sensing strategy in this
      design can be a simple but efficient approach for OFF-ON luminescent sensing of
      metal cations that inherently lack selective ligands.

PMID- 23151297
TI  - Hypovitaminosis A coupled to secondary bacterial infection in beef cattle.
AB  - BACKGROUND: Vitamin A is essential for normal growth, development, reproduction,
      cell proliferation, cell differentiation, immune function and vision.
      Hypovitaminosis A can lead to a series of pathological damage in animals. This
      report describes the case of hypovitaminosis A associated with secondary
      complications in calves. CASE PRESENTATION: From February to March in 2011, 2-and
      3-month old beef calves presented with decreased eyesight, apparent blindness and
      persistent diarrhea occurred in a cattle farm of Hubei province, China. Based on
      history inspection and clinical observation, we made a tentative diagnosis of
      hypovitaminosis A. The disease was confirmed as a congenital vitamin A deficiency
      by determination of the concentrations of vitamin A in serum and feed samples.
      Furthermore, pathological and microbiological examination showed that the disease
      was associated with pathogenic Escherichia coli (E. coli) infection and mucosal
      barriers damage in intestines. The corresponding treatments were taken
      immediately, and the disease was finally under control for a month. CONCLUSIONS:
      To our knowledge, this is the first report of hypovitaminosis A coupled to
      secondary infection of E. coli in beef cattle, advancing our knowledge of how
      vitamin A affects infection and immunity in animals. This study could also be
      contributed to scientific diagnosis and treatments of complex hypovitaminosis A
      in cattle.

PMID- 23151299
TI  - Work stress, life stress, and smoking among rural-urban migrant workers in China.
AB  - BACKGROUND: Stimulated by rapid modernization and industrialization, there is
      massive rural-urban migration in China. The migrants are highly susceptible to
      smoking and mental health problems. This study examined the association between
      both perceived work stress and perceived life stress with smoking behavior among
      this group during the period of migration. METHODS: Participants (n = 1,595) were
      identified through stratified, multi-stage, systematic sampling. Smoking status
      separated non-smokers from daily and occasional smokers, and migration history,
      work stress, and life stress were also measured. Analyses were conducted using
      the Chi-square test and multiple logistic regression. Two models were utilized.
      The first was the full model that comprised sociodemographic and migration
      related characteristics, as well as the two stress variables. In addressing
      potential overlap between life and work stress, the second model eliminated one
      of the two stress variables as appropriate. RESULTS: Overall smoking prevalence
      was 64.9% (95% CI: 62.4-67.2%). In the regression analysis, under the full model,
      migrants with high perceived life stress showed a 45% excess likelihood to be
      current smokers relative to low-stress counterparts (OR: 1.45; 95% CI: 1.05 -
      2.06). Applying the second model, which excluded the life stress variable,
      migrants with high perceived work stress had a 75% excess likelihood to be
      current smokers relative to opposites (OR: 1.75; 95% CI: 1.26-2.45). CONCLUSIONS:
      Rural-urban migrant workers manifested a high prevalence of both life stress and
      work stress. While both forms of stress showed associations with current smoking,
      life stress appeared to outweigh the impact of work stress. Our findings could
      inform the design of tobacco control programs that would target Chinese rural
      urban migrant workers as a special population.

PMID- 23151301
TI  - Life: asteroid target, witness from the early Earth, and ubiquitous effect on
      global geology.

PMID- 23151300
TI  - The miniaturized Raman system and detection of traces of life in halite from the
      Atacama Desert: some considerations for the search for life signatures on Mars.
AB  - Raman spectroscopy is being adopted as a nondestructive instrumentation for the
      robotic exploration of Mars to search for traces of life in the geological
      record. Here, miniaturized Raman spectrometers of two different types equipped
      with 532 and 785 nm lasers for excitation, respectively, were compared for the
      detection of microbial biomarkers in natural halite from the hyperarid region of
      the Atacama Desert. Measurements were performed directly on the rock as well as
      on the homogenized, powdered samples prepared from this material-the effects of
      this sample preparation and the excitation wavelength employed in the analysis
      are compared and discussed. From these results, 532 nm excitation was found to be
      superior for the analysis of powdered specimens due to its high sensitivity
      toward carotenoids and hence a higher capability for their detection at
      relatively low concentration in bulk powdered specimens. For the same reason,
      this wavelength was a better choice for the detection of carotenoids in direct
      measurements made on the rock samples. The 785 nm excitation wavelength, in
      contrast, proved to be more sensitive toward the detection of scytonemin.

PMID- 23151303
TI  - Is pocket ultrasound ready for prime time?

PMID- 23151302
TI  - Is bruxism a risk factor for dental implants? A systematic review of the
      literature.
AB  - PURPOSE: To systematically review the literature on the role of bruxism as a risk
      factor for the different complications on dental implant-supported
      rehabilitations. MATERIAL AND METHODS: A systematic search in the National
      Library of Medicine's Medline Database was performed to identify all peer
      reviewed papers in the English literature assessing the role of bruxism, as
      diagnosed with any other diagnostic approach (i.e., clinical assessment,
      questionnaires, interviews, polysomnography, and electromyography), as a risk
      factor for biological (i.e., implant failure, implant mobility, and marginal bone
      loss) or mechanical (i.e., complications or failures of either prefabricated
      components or laboratory-fabricated suprastructures) complications on dental
      implant-supported rehabilitations. The selected articles were reviewed according
      to a structured summary of the articles in relation to four main issues, viz.,
      "P" - patients/problem/population, "I" - intervention, "C" - comparison, and "O" 
      outcome. RESULTS: A total of 21 papers were included in the review and split
      into those assessing biological complications (n = 14) and those reporting
      mechanical complications (n = 7). In general, the specificity of the literature
      for bruxism diagnosis and for the study of the bruxism's effects on dental
      implants was low. From a biological viewpoint, bruxism was not related with
      implant failures in six papers, while results from the remaining eight studies
      did not allow drawing conclusions. As for mechanical complications, four of the
      seven studies yielded a positive relationship with bruxism. CONCLUSIONS: Bruxism
      is unlikely to be a risk factor for biological complications around dental
      implants, while there are some suggestions that it may be a risk factor for
      mechanical complications.

PMID- 23151304
TI  - A novel NOTCH1 PEST domain mutation in a case of chronic lymphocytic leukemia.

PMID- 23151305
TI  - TGF beta1 and related-Smads contribute to pulmonary metastasis of hepatocellular
      carcinoma in mice model.
AB  - BACKGROUND: Recent studies indicate that Transforming Growth Factor beta (TGF
      beta) correlated with pulmonary metastasis of cancers. However, the correlation
      between TGF beta and pulmonary metastasis of hepatocellular carcinoma (HCC) is
      till unknown. METHODS: We detected the in vitro and in vivo expression levels of
      TGF beta1/Smads by Real-time PCR and Western blot in MHCC97-H and MHCC97-L cell
      lines, which are HCC cell lines and have higher and lower pulmonary metastatic
      potential respectively. RESULTS: TGF beta1 mRNA level in MHCC97-L tumors were
      higher than that in MHCC97-H tumors, (2.81+/-1.61 vs. 1.24+/-0.96, P=0.002), TGF
      beta1 protein level in MHCC97-L tumors were also higher than that in MHCC97-H
      tumors (1.37+/-0.95 vs. 0.32+/-0.22, P<0.001). In addition, the TGF beta1 mRNA
      level positively correlated with pulmonary metastasis, and the relations between
      TGF beta1 and Smads were also found (R2=0.12 and 0.40, respectively).
      CONCLUSIONS: Our results suggest that TGF beta/ Smads promote pulmonary
      metastasis of HCC.

PMID- 23151306
TI  - First signal from a broadband cryogenic preamplifier cooled by circulating liquid
      nitrogen in a 7 T Fourier transform ion cyclotron resonance mass spectrometer.
AB  - Despite the outstanding performance of Fourier transform ion cyclotron/mass
      spectrometry (FTICR/MS), the complexity of the cellular proteome or natural
      compounds presents considerable challenges. Sensitivity is a key performance
      parameter of a FTICR mass spectrometer. By improving this parameter, the dynamic
      range of the instrument can be increased to improve the detection signal of low
      abundance compounds or fragment ion peaks. In order to improve sensitivity, a
      cryogenic detection system was developed by the KBSI (Korean Basic Science
      Institute) in collaboration with Stahl-Electronics (Mettenheim, Germany). A
      simple, efficient liquid circulation cooling system was designed and a cryogenic
      preamplifier implemented inside a FTICR mass spectrometer. This cooling system
      circulates a cryoliquid from a Dewar to the "liquid circulation unit" through a
      CF flange to cool a copper block and a cryopreamplifier; the cooling medium is
      subsequently exhausted into the air. The cryopreamplifier can be operated over a
      very wide temperature range, from room temperature to low temperature
      environments (4.2 K). First, ion signals detected by the cryopreamplifier using a
      circulating liquid nitrogen cooling system were observed and showed a signal-to
      noise ratio (S/N) about 130% better than that obtained at room temperature.

PMID- 23151307
TI  - Immune correlates of aging in outdoor-housed captive rhesus macaques (Macaca
      mulatta).
AB  - BACKGROUND: Questions remain about whether inflammation is a cause, consequence,
      or coincidence of aging. The purpose of this study was to define baseline
      immunological characteristics from blood to develop a model in rhesus macaques
      that could be used to address the relationship between inflammation and aging.
      Hematology, flow cytometry, clinical chemistry, and multiplex cytokine/chemokine
      analyses were performed on a group of 101 outdoor-housed captive rhesus macaques
      ranging from 2 to 24 years of age, approximately equivalent to 8 to 77 years of
      age in humans. RESULTS: These results extend earlier reports correlating changes
      in lymphocyte subpopulations and cytokines/chemokines with increasing age. There
      were significant declines in numbers of white blood cells (WBC) overall, as well
      as lymphocytes, monocytes, and polymorphonuclear cells with increasing age. Among
      lymphocytes, there were no significant declines in NK cells and T cells, whereas
      B cell numbers exhibited significant declines with age. Within the T cell
      populations, there were significant declines in numbers of CD4+ naive T cells and
      CD8+ naive T cells. Conversely, numbers of CD4+CD8+ effector memory and
      CD8+effector memory T cells increased with age. New multiplex analyses revealed
      that concentrations of a panel of ten circulating cytokines/chemokines, IFNgamma,
      IL1b, IL6, IL12, IL15, TNFalpha, MCP1, MIP1alpha, IL1ra, and IL4, each
      significantly correlated with age and also exhibited concordant pairwise
      correlations with every other factor within this group. To also control for
      outlier values, mean rank values of each of these cytokine concentrations in
      relation to age of each animal and these also correlated with age. CONCLUSIONS: A
      panel of ten cytokines/chemokines were identified that correlated with aging and
      also with each other. This will permit selection of animals exhibiting relatively
      higher and lower inflammation status as a model to test mechanisms of
      inflammation status in aging with susceptibility to infections and vaccine
      efficacy.

PMID- 23151309
TI  - Protective effect of heparin in the end organ ischemia/reperfusion injury of the
      lungs and heart.
AB  - BACKGROUND: Ischemia/reperfusion (I/R) injury is harmful to the cardiovascular
      system and is responsible for the inflammatory response and multiple organ
      dysfunctions. In this study we investigated the effect of activated clotting time
      level on the aortic cross-clamping triggers a systemic inflammatory response and
      it effects to lungs and heart. METHODS: End organ concentrations of interleukin-6
      (IL-6), myeloperoxidase (MPO) and heat shock protein 70 (HSP-70) were determined
      in four groups of Spraque Dawley rats: ischemic control (operation with cross
      clamping received IP of 0.9% saline at 2 ml/kg n=7) Sham (operation without cross
      clamping, n=7), heparin (ACT level about 200), High dose heparin (ACT level up to
      600) The infrarenal aorta was clamped for 45 minutes by a mini cross clamp
      approximately 1cm below the renal artery and 1cm iliac bifurcation in all groups
      without sham group. Heparin was given intraperitoneal (IP) before the procedure.
      All rats were sacrificed 48 h later. In a second experiment, the effects of I/R
      on remote organs (lungs and heart) were harvested for analysis. We evaluated
      tissue levels of myeloperoxidase, interleukin-6, and heat shock protein (HSP-70)
      were analyzed as markers oxidative stress and inflammation. Histological analyses
      of the organs were performed. RESULTS: The lungs paranchymal MPO and HSP-70
      levels significantly decreased (p<0.05), but IL-6 level was not significant
      (p>0.05) in heparinized and high dose heparinized groups when compared to
      ischemic control group. Histopathological evaluation as edema, cell degeneration,
      inflammation statistically significantly decreased in both group heparinized and
      high dose heparinized compared with ischemic control group (p<0.05). The heart
      paranchymal MPO levels significantly decreased in heparinized and high dose
      heparinized groups when compared to ischemic control group (p=0.023). IL-6, HSP
      70 levels were not significant heparinized and high dose heparinized groups when
      compared to ischemic control group (p=0.0489, p=0.0143). Histopathological
      evaluation as degeneration statistically significantly decreased in both group
      heparinized and High dose heparinized compared with ischemic control group
      (p=0.005). CONCLUSION: Heparin decreased remote organs injury on the lung and
      heart after ischemia/reperfusion of infra-renal section of the body in the rat
      model. So, we should be balance to act level for avoid to I/R injury per
      operative and early post operative period as providing ACT level nearly 200.

PMID- 23151310
TI  - Conformational analysis of thioflavin T bound to the surface of amyloid fibrils.
AB  - The interaction of small molecules with the surface of amyloid assemblies is
      important for the detection and inhibition of amyloid formation. Thioflavin T
      (ThT), a small molecular rotor, has been used for the detection of amyloid
      fibrils for over half a century. The basis for detection is simple in that in the
      presence of fibrils the fluorescence of ThT is dramatically enhanced. The
      mechanism for this enhancement is not well understood but may depend on the
      determination of the conformation of ThT bound to the fibril surface. Here, we
      first use solution-state (1)H NMR to show that the on-off binding of ThT to the
      surface of insulin amyloid fibrils correlates with the enhancement of ThT
      fluorescence. We then show that the conformation of surface-bound ThT is twisted.
      The implications of this result in light of recent experimental and computational
      studies of the binding of ThT to amyloid or amyloid-like assemblies are
      discussed.

PMID- 23151311
TI  - Drastic differences between the local and the average structures of Sr2MSbO5.5 (M
      = Ca, Sr, Ba) oxygen-deficient double perovskites.
AB  - For many disordered materials, knowing their average crystal structure is
      insufficient for explaining and predicting their macroscopic properties. It has
      been found that a description of the short-range atomic arrangements is needed to
      understand such materials. In order to understand the conduction pathways in
      ionic conductors which have random distributions of vacancies it is imperative to
      know the local structures which are present. In this study the local structures
      of three oxygen-deficient double perovskites, Sr(2)MSbO(5.5) (M = Ca, Sr, Ba),
      have been investigated by neutron pair distribution function analysis. The ions
      in these compounds are all found to have local coordination environments which
      are radically different than those given by their average structures. While there
      is no long-range ordering of the oxygen vacancies in these compounds, a
      considerable amount of short-range order does exist. The conditions which drive
      the short-range ordering are discussed as are the possible mechanisms for
      achieving it. It is proposed that the SbO(5) polyhedra form distorted trigonal
      bipyramids by moving oxygen atoms into interstitial positions. In the M = Sr
      compound 45 degrees  rotations of SbO(6) octahedra are also present, which add
      additional oxygen atoms into the interstitial sites. Large displacements of the
      Ca(2+), Sr(2+), and Ba(2+) cations are also present, the directions of which are
      correlated with the occupancies of the interstitial oxygen sites. Reverse Monte
      Carlo modeling of the pair distribution function data has provided the actual
      bond length distributions for the cations.

PMID- 23151308
TI  - Molecular evolution and phylogenetics of rodent malaria parasites.
AB  - BACKGROUND: Over the last 6 decades, rodent Plasmodium species have become key
      model systems for understanding the basic biology of malaria parasites. Cell and
      molecular parasitology have made much progress in identifying genes underpinning
      interactions between malaria parasites, hosts, and vectors. However, little
      attention has been paid to the evolutionary genetics of parasites, which provides
      context for identifying potential therapeutic targets and for understanding the
      selective forces shaping parasites in natural populations. Additionally,
      understanding the relationships between species, subspecies, and strains, is
      necessary to maximize the utility of rodent malaria parasites as medically
      important infectious disease models, and for investigating the evolution of host
      parasite interactions. RESULTS: Here, we collected multi-locus sequence data from
      58 rodent malaria genotypes distributed throughout 13 subspecies belonging to P.
      berghei, P. chabaudi, P. vinckei, and P. yoelii. We employ multi-locus methods to
      infer the subspecies phylogeny, and use population-genetic approaches to
      elucidate the selective patterns shaping the evolution of these organisms. Our
      results reveal a time-line for the evolution of rodent Plasmodium and suggest
      that all the subspecies are independently evolving lineages (i.e. species). We
      show that estimates of species-level polymorphism are inflated if subspecies are
      not explicitly recognized, and detect purifying selection at most loci.
      CONCLUSIONS: Our work resolves previous inconsistencies in the phylogeny of
      rodent malaria parasites, provides estimates of important parameters that relate
      to the parasite's natural history and provides a much-needed evolutionary context
      for understanding diverse biological aspects from the cross-reactivity of immune
      responses to parasite mating patterns.

PMID- 23151312
TI  - EBV-positive diffuse large B-cell lymphoma in a patient with primary Sjogren's
      syndrome and membranous glomerulonephritis.
AB  - BACKGROUND: Sjogren's syndrome is a systemic autoimmune disease in which
      lymphatic cells destroy the salivary and lacrimal glands. Glomerulonephritis is
      thought to be a rare occurrence in primary Sjogren's syndrome. Furthermore,
      concurrent glomerular involvement and lymphoma in patients with Sjogren's
      syndrome has seldom been reported. CASE PRESENTATION: A 52-year-old woman with
      primary Sjogren's syndrome developed membranous glomerulonephritis and Epstein
      Barr virus-positive diffuse large B-cell lymphoma (DLBCL). She was diagnosed with
      Sjogren's syndrome based on the dry eyes, dry mouth, positive anti-nuclear
      antibody test, anti-Ro (SS-A) antibody, salivary gland biopsy, and salivary
      scintigraphy. Moreover, renal biopsy confirmed the diagnosis of membranous
      glomerulonephritis. Three months later, her small bowel was perforated with
      pneumoperitoneum, and the biopsy revealed Epstein-Barr virus-positive DLBCL.
      CONCLUSIONS: We observed the first case of primary Sjogren's syndrome associated
      with Epstein-Barr Virus-positive DLBCL and membranous glomerulonephritis. Because
      of the possibility of malignancy-associated membranous glomerulonephritis in
      patients with primary Sjogren's syndrome, we should be careful and examine such
      patients for hidden malignancy.

PMID- 23151313
TI  - The first row anomaly and recoupled pair bonding in the halides of the late p
      block elements.
AB  - The dramatic differences between the properties of molecules formed from the late
      p-block elements of the first row of the periodic table (N-F) and those of the
      corresponding elements in subsequent rows is well recognized as the first row
      anomaly. Certain properties of the atoms, such as the relative energies and
      spatial extents of the ns and np orbitals, can explain some of these differences,
      but not others.  In this Account, we summarize the results of our recent
      computational studies of the halides of the late p-block elements. Our studies
      point to a single underlying cause for many of these differences: the ability of
      the late p-block elements in the second and subsequent rows of the periodic table
      to form recoupled pair bonds and recoupled pair bond dyads with very
      electronegative ligands. Recoupled pair bonds form when an electron in a singly
      occupied ligand orbital recouples the pair of electrons in a doubly occupied lone
      pair orbital on the central atom, leading to a central atom-ligand bond.
      Recoupled pair bond dyads occur when a second ligand forms a bond with the
      orbital left over from the initial recoupled pair bond.  Recoupled pair bonds and
      recoupled pair bond dyads enable the late p-block elements to form remarkably
      stable hypervalent compounds such as PF(5) and SF(6) and lead to unexpected
      excited states in smaller halides of the late p-block elements such as SF and
      SF(2). Recoupled pair bonding also causes the F(n-1)X-F bond energies to
      oscillate dramatically once the normal valences of the central atoms have been
      satisfied. In addition, recoupled pair bonding provides a lower-energy pathway
      for inversion in heavily fluorinated compounds (PF(3) and PF(2)H, but not PH(2)F
      and PH(3)) and leads to unusual intermediates and products in reactions involving
      halogens and late p-block element compounds, such as (CH(3))(2)S + F(2). 
      Although this Account focuses on the halides of the second row, late p-block
      elements, recoupled pair bonds and recoupled pair bond dyads are important in the
      chemistry of p-block elements beyond the second row (As, Se, and Br) and for
      compounds of these elements with other very electronegative ligands, such as OH
      and O. Knowledge of recoupled pair bonding is thus critical to understanding the
      properties and reactivity of molecules containing the late p-block elements
      beyond the first row.

PMID- 23151314
TI  - Can neonatal lung ultrasound monitor fluid clearance and predict the need of
      respiratory support?
AB  - INTRODUCTION: At birth, lung fluid is rapidly cleared to allow gas exchange. As
      pulmonary sonography discriminates between liquid and air content, we have used
      it to monitor extrauterine fluid clearance and respiratory adaptation in term and
      late preterm neonates. Ultrasound data were also related to the need for
      respiratory support. METHODS: Consecutive infants at 60 to 120 minutes after
      birth underwent lung echography. Images were classified using a standardized
      protocol of adult emergency medicine with minor modifications. Neonates were
      assigned to type 1 (white lung image), type 2 (prevalence of comet-tail artifacts
      or B-lines) or type 3 profiles (prevalence of horizontal or A lines). Scans were
      repeated at 12, 24 and 36 hours. The primary endpoint was the number of infants
      admitted to the neonatal ICU (NICU) by attending staff who were unaware of the
      ultrasound. Mode of respiratory support was also recorded. RESULTS: A total of
      154 infants were enrolled in the study. Fourteen neonates were assigned to the
      type 1, 46 to the type 2 and 94 to the type 3 profile. Within 36 hours there was
      a gradual shift from types 1 and 2 to type 3. All 14 type 1 and 4 type 2 neonates
      were admitted to the NICU. Sensitivity was 77.7%, specificity was 100%, positive
      predictive value was 100%, negative predictive value was 97%. Four type 1 infants
      were mechanically ventilated. CONCLUSIONS: In the late preterm and term neonate,
      the lung ultrasound scan follows a reproducible pattern that parallels the
      respiratory status and can be used as a predictor of respiratory support.

PMID- 23151315
TI  - Variant TREM2 as risk factor for Alzheimer's disease.

PMID- 23151316
TI  - Exogenous hyperinsulinemia and atherosclerosis in type 1 diabetic patients.

PMID- 23151317
TI  - Affective decision-making on the Iowa gambling task in children and adolescents
      with fetal alcohol spectrum disorders.
AB  - Individuals with fetal alcohol spectrum disorders (FASD) have difficulties with
      cognitive-based executive function (EF) tasks. The goal of the present study was
      to determine if children with FASD have impairments on the Iowa Gambling Task
      (IGT), which measures affective EF (i.e., decision-making and risk-taking).
      Individuals with FASD (n = 31) and healthy controls (n = 31), aged 8-17 completed
      the IGT. Children with FASD were significantly impaired on the IGT compared to
      controls. Over the course of the task, control scores improved, whereas children
      with FASD exhibited an overall decrease in scores. Scores increased significantly
      with age in the control group but did not differ significantly with age for FASD
      participants. Children with FASD exhibited decision-making and risk-taking
      impairments on a hot EF task. Children with FASD did not appear to learn from
      negative experiences and shift to making more positive decisions over time and
      their performance did not improve with age. The implications of poor task
      performance and a lack of age-related findings in children with FASD are
      discussed.

PMID- 23151318
TI  - Revaluing unmanaged forests for climate change mitigation.
AB  - BACKGROUND: Unmanaged or old-growth forests are of paramount importance for
      carbon sequestration and thus for the mitigation of climate change among further
      implications, e.g. biodiversity aspects. Still, the importance of those forests
      for climate change mitigation compared to managed forests is under controversial
      debate. We evaluate the adequacy of referring to CO2 flux measurements alone and
      include external impacts on growth (nitrogen immissions, increasing temperatures,
      CO2 enrichment, changed precipitation patterns) for an evaluation of central
      European forests in this context. RESULTS: We deduce that the use of CO2 flux
      measurements alone does not allow conclusions on a superiority of unmanaged to
      managed forests for mitigation goals. This is based on the critical consideration
      of uncertainties and the application of system boundaries. Furthermore, the
      consideration of wood products for material and energetic substitution obviously
      overrules the mitigation potential of unmanaged forests. Moreover, impacts of
      nitrogen immissions, CO2 enrichment of the atmosphere, increasing temperatures
      and changed precipitation patterns obviously lead to a meaningful increase in
      growth, even in forests of higher age. CONCLUSIONS: An impact of unmanaged
      forests on climate change mitigation cannot be valued by CO2 flux measurements
      alone. Further research is needed on cause and effect relationships between
      management practices and carbon stocks in different compartments of forest
      ecosystems in order to account for human-induced changes. Unexpected growth rates
      in old-growth forests - managed or not - can obviously be related to external
      impacts and additionally to management impacts. This should lead to the
      reconsideration of forest management strategies.

PMID- 23151319
TI  - Tumorigenesis role and clinical significance of DJ-1, a negative regulator of
      PTEN, in supraglottic squamous cell carcinoma.
AB  - BACKGROUND: DJ-1 can induce the tumor cell proliferation and invasion via down
      regulating PTEN in many malignant tumors, and correlated to prognostic
      significance. However, the tumorigenesis role and clinical significance of DJ-1
      in supraglottic squamous cell carcinoma (SSCC) is unclear. We aimed to evaluate
      the DJ-1 the relationship between DJ-1 and clinicopathological data including
      patient survival. METHODS: The expression of DJ-1 and PTEN in SSCCs (52) and
      adjacent non-cancerous tissues (42) was assessed by immunohistochemistry (IHC),
      and the relationship between DJ-1 and clinicopathological data was analyzed.
      RESULTS: DJ-1 was detected mainly in SSCCs (88.5%) and less frequently in
      adjacent non-cancerous tissues (21.0%). PTEN expression was detected in 46.2% of
      SSCCs and in 90.5% of adjacent non-cancerous tissues. DJ-1 expression was linked
      to nodal status (P = 0.009), a highly significant association of DJ-1 expression
      with shortened patient overall survival (5-year survival rate 88.0% versus 53.9%;
      P = 0.007; log rank test) was demonstrated. CONCLUSIONS: Our data suggested that
      DJ-1 over-expression was linked to nodal status, and might be an independent
      prognostic marker for patients with SSCC.

PMID- 23151320
TI  - Scaffold hopping strategy toward original pyrazolines as selective CB2 receptor
      ligands.
AB  - In line of a scaffold hopping strategy of pyrazole structures, especially known
      as potent CB(2) receptor antagonists, we exploited an original and convergent
      synthesis of a new class of C4-benzyl pyrazolines and derivatives from readily
      available hydrazones and enones (two or three steps). Making use of a mixture of
      resin supported reagents strategy an efficient domino process allowed the easy
      construction of various dihydropyrazoles in 63-83% yields. The obtained family of
      pyrazolines featured significant hCB(2)/hCB(1) selectivity in favor of hCB(2)
      receptors while more than 1000-3000 nM affinity was only measured for hCB(1)
      receptors. This is closely related to pyrazole SR144528 inverse
      agonist/antagonist, although a partial agonist behavior in the [(35)S]-GTPgammaS
      binding assay was mainly measured in our case pointing out a functional switch in
      action. Furthermore, this hCB(2) selectivity is unique within the pyrazoline CB
      ligands although the affinity ranging from 251 to 689 nM remains to be improved
      which give, however, an opportunity for further structure-activity relationship.

PMID- 23151321
TI  - Synthesis and in vitro antiproliferative activity of new 11-aminoalkylamino
      substituted chromeno[2,3-b]indoles.
AB  - To search for new biological activities of the chromeno[2,3-b]indoles, the 5-oxa
      analog of the indolo[2,3-b]quinolines that are known to have a potent antitumor
      activity, a series of 11-amino derivatives with various substituents at the C-2
      position were prepared. The synthesis of the chromeno[2,3-b]indole structure
      involves the cyclization of 2-phenoxy-3-indolecarboxylates 3, accessible from the
      indole-3-carboxylate 1 and phenols 2, producing the chromeno[2,3-b]indol-11(6H)
      ones 4, which is followed by dehydroxychlorination with phosphorus oxychloride to
      afford the 11-chlorochromeno[2,3-b]indoles 5. The treatment of 5 with various
      amines produced the corresponding 11-aminated chromeno[2,3-b]indoles 6, while
      some of the 11-omega-aminoalkylamino derivatives 6 were transformed into the 11
      omega-sulfonylaminoalkylamino derivatives 8. The antiproliferative activity of
      these 11-aminochromeno[2,3-b]indoles 6 and 8 in vitro were tested using MV4-11
      (human leukemia), A549 (lung cancer), HCT116 (colon cancer), and the normal mice
      fibroblast (BALB/3T3) and their potencies were described.

PMID- 23151322
TI  - Facile water promoted synthesis of 1,2,3-triazolyl dihydropyrimidine-2-thione
      hybrids - highly potent antibacterial agents.
AB  - An elegant and efficient synthesis of hitherto novel 1,2,3-triazolyl
      dihydropyrimidine-2-thione hybrids has been accomplished for the first time in a
      green solvent viz. water. The hybrid molecules exhibit significant antibacterial
      activity when screened against four human pathogens viz. Streptococcus pneumonia,
      Staphylococcus aureus, Pseudomonas aeruginosa and Salmonella typhi. In comparison
      to the commercially marketed tetracycline, some of them were equally potent and a
      few more potent.

PMID- 23151323
TI  - Synthesis and characterization of the europium(III) pentakis(picrate) complexes
      with imidazolium countercations: structural and photoluminescence study.
AB  - Six new lanthanide complexes of stoichiometric formula (C)(2)[Ln(Pic)(5)]--where
      (C) is a imidazolium cation coming from the ionic liquids 1-butyl-3
      methylimidazolium picrate (BMIm-Pic), 1-butyl-3-ethylimidazolium picrate (BEIm
      Pic), and 1,3-dibutylimidazolium picrate (BBIm-Pic), and Ln is Eu(III) or Gd(III)
      ions--have been prepared and characterized. To the best of our knowledge, these
      are the first cases of Ln(III) pentakis(picrate) complexes. The crystal
      structures of (BEIm)(2)[Eu(Pic)(5)] and (BBIm)(2)[Eu(Pic)(5)] compounds were
      determined by single-crystal X-ray diffraction. The [Eu(Pic)(5)](2-) polyhedra
      have nine oxygen atoms coordinated to the Eu(III) ion, four oxygen atoms from
      bidentate picrate, and one oxygen atom from monodentate picrate. The structures
      of the Eu complexes were also calculated using the sparkle model for lanthanide
      complexes, allowing an analysis of intramolecular energy transfer processes in
      the coordination compounds. The photoluminescence properties of the Eu(III)
      complexes were then studied experimentally and theoretically, leading to a
      rationalization of their emission quantum yields.

PMID- 23151324
TI  - Neuropsychological, functional, and behavioral outcome in South African traumatic
      brain injury litigants.
AB  - Few studies address the extent to which, during the process of litigation,
      individuals with moderate-to-severe traumatic brain injury might malinger in
      their performance on neuropsychological assessment batteries. This study explored
      whether financial settlement influenced neuropsychological test performance and
      activities of daily living in litigants (N = 31) who were tested and interviewed
      both during litigation and 1 year or more after case settlement. Results showed
      that neuropsychological test scores did not change from assessment during
      forensic proceedings to assessment after settlement. Although some improvement
      was evident in activities of daily living, the gains were small and their
      clinical significance questionable. We found no evidence that individuals with
      moderate-to-severe TBI, despite clear potential for secondary gain, malingered or
      delivered sub-optimal effort during neuropsychological evaluation taking place in
      the context of litigation.

PMID- 23151326
TI  - [A woman with skin abnormalities around the mouth].
AB  - A 33-year-old healthy woman consulted her dermatologist when an acute and painful
      perioral pustular dermatosis erupted one day after she had taken azitromycin for
      a throat infection. A preliminary diagnosis of acute localized exanthematous
      pustulosis (ALEP) was made, which was later confirmed by cultures and
      histopathological examination. Medication was cessated immediately and the
      dermatosis disappeared completely afterwards.

PMID- 23151325
TI  - A survey on infection management practices in Italian ICUs.
AB  - INTRODUCTION: An online survey was conducted to characterize current infection
      management practices in Italian intensive care units (ICUs), including the
      antibacterial and antifungal drug regimens prescribed for various types of
      infections. METHODS: During February and March 2011, all 450 ICUs in public
      hospitals in Italy were invited to take part in an online survey. The
      questionnaire focused on ICU characteristics, methods used to prevent, diagnose,
      and treat infections, and antimicrobials prescribing policies. The frequency of
      each reported practice was calculated as a percentage of the total number of
      units answering the question. The overall response rate to the questionnaire was
      38.8% (175 of the 450 ICUs contacted) with homogeneous distribution across the
      country and in terms of unit type. RESULTS: Eighty-eight percent of the
      responding facilities performed periodical surveillance cultures on all patients.
      In 71% of patients, cultures were also collected on admission.
      Endotracheal/bronchial aspirates were the most frequently cultured specimens at
      both time points. Two-thirds of the responding units had never performed
      screening cultures for methicillin-resistant Staphylococcus aureus. Around 67% of
      the ICUs reported the use of antimicrobial de-escalation strategies during the
      treatment phase. In general, the use of empirical antimicrobial drug regimens was
      appropriate. Although the rationale for the choice was not always clearly
      documented, the use of a combination therapy was preferred over antibiotic
      monotherapy. The preferred first-line agents for invasive candidiasis were
      fluconazole and an echinocandin (64% and 25%, respectively). Two-thirds of the
      ICUs monitored vancomycin serum levels and administered it by continuous infusion
      in 86% of cases. For certain antibiotics, reported doses were too low to ensure
      effective treatment of severe infections in critically ill patients; conversely,
      inappropriately high doses were administered for certain antifungal drugs.
      CONCLUSIONS: Although infection control policies and management practices are
      generally appropriate in Italian ICUs, certain aspects, such as the extensive use
      of multidrug empirical regimens and the inappropriate antimicrobial dosing,
      deserve careful management and closer investigation.

PMID- 23151327
TI  - [Lung cancer staging by endobronchial ultrasound with transbronchial needle
      aspiration].
AB  - OBJECTIVE: To determine the diagnostic yield of endobronchial ultrasound with
      transbronchial needle aspiration (EBUS-TBNA) and to investigate the number of
      cervical mediastinoscopies that could be avoided when this technique was used as
      the initial modality in the invasive mediastinal staging of lung cancer. DESIGN:
      Retrospective cohort study. METHOD: At the St. Antonius Hospital, Nieuwegein, the
      Netherlands, results from all patients who had undergone EBUS-TBNA for
      mediastinal staging in lung cancer from September 2008 to January 2011 were
      collected. If metastases in the mediastinal lymph nodes had been demonstrated by
      EBUS-TBNA, no indication for additional mediastinoscopy ensued. The diagnostic
      yield of EBUS-TBNA as well as the number of mediastinoscopies that had been
      avoided, were calculated. RESULTS: EBUS-TBNA had been used for mediastinal
      staging in lung cancer in 77 patients. In 39 of these 77 patients (51%),
      mediastinal lymph node metastases was found using EBUS-TBNA and mediastinoscopy
      could thus be avoided. In 9 out of 38 (24%) patients whose EBUS-TBNA cytology
      results were found to be either benign or not representative, mediastinoscopy or
      endoscopic ultrasound eventually did reveal mediastinal lymph node metastases. In
      13 of these 38 patients (34%), no additional cytologic or histologic testing was
      performed. Diagnostic yield was calculated for the two scenarios. The sensitivity
      and negative-predictive values for EBUS-TBNA were 64-81% and 42-76%,
      respectively. CONCLUSION: In more than 50% of lung cancer patients with suspected
      mediastinal lymph node metastases, cervical mediastinoscopy can be avoided when
      EBUS-TBNA is used. This examination is the technique of first choice for the
      invasive staging of the mediastinum in lung cancer, but it can not replace
      mediastinoscopy completely.

PMID- 23151329
TI  - [Smoking during pregnancy: trends between 2001 and 2010].
AB  - OBJECTIVE: To establish trends in the prevalence of smoking during pregnancy
      between 2001 and 2010 and to relate these to differences in educational gradient
      in the Netherlands. DESIGN: National surveys. METHOD: In 2001, 2002, 2003, 2005,
      2007 and 2010, 28,720 questionnaires were handed out to mothers with infants aged
      up to 6 months at periodic check-ups at well baby clinics. A total of 16,358
      (57%) mothers completed this questionnaire. RESULTS: Between 2001 and 2010, the
      number of women who smoked daily during their pregnancy dropped by half. In 2010
      6.3% (95% CI: 5.0-7.6) smoked. The prevalence of smoking was highest among
      mothers with a low level of education (13.8% in 2010; 95% CI 9.3-18.4%) and
      lowest among mothers with a high level of education (2.4% in 2010; 95% CI 1.2
      3.6). Four percent of pregnant smokers stopped smoking during pregnancy. Women
      limited the median number of ten cigarettes per day during the six months prior
      to pregnancy to five per day during pregnancy. The difference in prevalence of
      smoking in pregnancy between women with a low level of education and those with a
      high level of education was 18.9% in 2001 and 11.4% in 2010. The difference in
      smoking prevalence between mothers with an average level of education and mothers
      with a higher level education was 6.5% in 2001 and 5.4% in 2010. CONCLUSION:
      Between 2001 and 2010, the percentage of women who smoked throughout pregnancy
      dropped by half. In 2010, 6.3% of Dutch pregnant women were still smoking. The
      prevalence of smoking differed strongly between different levels of education and
      this difference did not change during the study.

PMID- 23151330
TI  - [Competing risks in clinical research].
AB  - In clinical research, study populations are often followed up until the
      occurrence of a certain outcome, such as breast cancer or death. Survival
      analysis, used to analyse the time-to-event data, is usually focused on one
      particular event; however, study participants may experience other events that
      prevent the event of interest from occurring. This is a situation of competing
      risks. An example is the risk of death in a study investigating breast cancer
      recurrence, as women who have died without having recurrent disease are no longer
      at risk of this recurrent disease. Competing risks can lead to biased results if
      not taken into account. Competing risks are important in studies including
      patients with a high risk of varying clinical outcomes, and in those studies with
      a long follow-up period. If competing risks are present, the competing outcomes
      can be combined into one outcome measure or should be taken into account in
      adapted survival analysis.

PMID- 23151334
TI  - [Ileus due to oranges in Meckel's diverticulum].
AB  - BACKGROUND: A Meckel's diverticulum is a remnant of the primitive bowel and the
      yolk sac which occurs in 1-5% of the population. It causes problems in only very
      few people. CASE DESCRIPTION: A 39-year-old man developed acute abdominal pain
      after eating two oranges. The cause of the pain was found during a lower
      abdominal laparotomy - the small bowel was obstructed by a Meckel's diverticulum
      and a phytobezoar composed of orange fibres. Both were removed surgically.
      CONCLUSION: A symptomatic Meckel's diverticulum should be removed; however, in an
      asymptomatic Meckel's diverticulum this approach is controversial. One of the
      problems that can arise is an obstructive ileus. Patients who in the past have
      had an obstructive ileus resulting from a phytobezoar are advised to avoid eating
      large quantities of fruit rich in fibre and to chew very well.

PMID- 23151335
TI  - [Youth Healthcare guideline 'Skin disorders'].
AB  - There is a high incidence of skin disorders; these are also frequently
      encountered within Youth Healthcare (YHC). Some skin disorders are caused by an
      underlying disease, syndrome or child abuse. Therefore, detection of these causes
      in an early stage is important. Skin disorders can have a huge psychosocial
      impact on both child and parents. This is one of the reasons why prevention,
      detection, diagnosis, treatment, referral, and uniform advice and guidance are of
      great importance. The YHC Guideline examines counselling and advice, criteria for
      referral to primary or secondary healthcare, and skincare in general. It also
      describes the disorders that should be actively detected. The Guideline also
      looks at specific aspects of dark skins and ethnic diversity, and the impact of
      skin disorders on general wellbeing. The accompanying web-based tool includes
      argumentation and opinions from experts on more than 75 skin disorders, including
      illustrations and decision trees, to aid the drawing up of a treatment plan.

PMID- 23151336
TI  - Restructuring emergency surgery staffing improves outcomes and reduces costs.

PMID- 23151337
TI  - Molecular-based detection of the gastrointestinal pathogen Campylobacter
      ureolyticus in unpasteurized milk samples from two cattle farms in Ireland.
AB  - Campylobacter jejuni and coli are collectively regarded as the most prevalent
      cause of bacterial foodborne illness worldwide. An emerging species,
      Campylobacter ureolyticus has recently been detected in patients with
      gastroenteritis, however, the source of this organism has, until now, remained
      unclear. Herein, we describe the molecular-based detection of this pathogen in
      bovine faeces (1/20) and unpasteurized milk (6/47) but not in poultry (chicken
      wings and caeca). This is, to the best of our knowledge, the first report of the
      presence of this potential gastrointestinal pathogen in an animal source,
      possibly suggesting a route for its transmission to humans.

PMID- 23151338
TI  - RMol: a toolset for transforming SD/Molfile structure information into R objects.
AB  - BACKGROUND: The graph-theoretical analysis of molecular networks has a long
      tradition in chemoinformatics. As demonstrated frequently, a well designed format
      to encode chemical structures and structure-related information of organic
      compounds is the Molfile format. But when it comes to use modern programming
      languages for statistical data analysis in Bio- and Chemoinformatics, R as one of
      the most powerful free languages lacks tools to process Molfile data collections
      and import molecular network data into R. RESULTS: We design an R object which
      allows a lossless information mapping of structural information from Molfiles
      into R objects. This provides the basis to use the RMol object as an anchor for
      connecting Molfile data collections with R libraries for analyzing graphs.
      Associated with the RMol objects, a set of R functions completes the toolset to
      organize, describe and manipulate the converted data sets. Further, we bypass R
      typical limits for manipulating large data sets by storing R objects in bz
      compressed serialized files instead of employing RData files. CONCLUSIONS: By
      design, RMol is a R toolset without dependencies to other libraries or
      programming languages. It is useful to integrate into pipelines for serialized
      batch analysis by using network data and, therefore, helps to process sdf-data
      sets in R efficiently. It is freely available under the BSD licence. The script
      source can be downloaded from http://sourceforge.net/p/rmol-toolset.

PMID- 23151339
TI  - How vegetables make the meal: their hedonic and heroic impact on perceptions of
      the meal and of the preparer.
AB  - OBJECTIVE: Although most parents know that vegetables are healthful, vegetables
      are served at only 23% of American dinners. If added nutrition is not a
      sufficient motivation, might a parent be more inspired to serve vegetables if
      doing so improved either the taste of the entree or how loving and thoughtful the
      server would be perceived? The present paper details two studies which
      investigated whether serving vegetables changes the perception of the cook and
      the perception of an entree's taste. DESIGN: In Study 1, people evaluated the
      personality of a cook who either did or did not include a vegetable in a family
      dinner. In Study 2, five different meals that either included or did not include
      a vegetable were rated in terms of the taste of the entree and of the whole meal.
      SETTING: US-based online survey. SUBJECTS: American mothers (n 500), ranging in
      age from 18 to 65 years (mean age 38.4 years), with at least two children under
      the age of 18 years living at home. RESULTS: Serving vegetables improved taste
      expectations for the entree as well as for the whole meal. Additionally, serving
      a vegetable with a meal also enhanced perceptions of the meal preparer. They were
      evaluated as being more thoughtful and attentive as well as less lazy, boring and
      self-absorbed. CONCLUSIONS: These two studies show new hedonic and heroic
      motivations for serving vegetables: (i) they increase the hedonic appeal of the
      meal and (ii) they increase the heroic appeal of the cook. More vegetables are
      likely to be served with a meal if preparers know that the addition of vegetables
      makes them appear to be both a better cook and a better person.

PMID- 23151340
TI  - Chromosomal Aberrations in ETV6/RUNX1-positive Childhood Acute Lymphoblastic
      Leukemia using 244K Oligonucleotide Array Comparative Genomic Hybridization.
AB  - BACKGROUND: Acute lymphoblastic leukemia (ALL) is a heterogeneous form of
      hematological cancer consisting of various subtypes. We are interested to study
      the genetic aberration in precursor B-cell ALL with specific t(12;21)
      translocation in childhood ALL patients. A high resolution 244K array-based
      Comparative Genomic Hybridization (array-CGH) was used to study eleven ETV6/RUNX1
      positive childhood acute lymphoblastic leukemia (ALL) patients. RESULT: 155
      chromosomal aberrations (119 losses, 36 gains) were reported in the array
      findings, corresponding to 76.8% deletions and 23.2% amplifications. The ETV6
      gene deletion occurred in 4 of the patients, corresponding to 45% of the sample.
      The most common alterations above 1 Mb were deletion 6q (13%), 12p (12%) and 9p
      (8%), and duplication 4q (6%) and Xq (4%). Other genes important in ALL were also
      identified in this study including RUNX1, CDKN2A, FHIT, and PAX5. The array-CGH
      technique was able to detect microdeletion as small as 400 bp. CONCLUSION: The
      results demonstrate the usefulness of high resolution array-CGH as a
      complementary tool in the investigation of ALL.

PMID- 23151341
TI  - Dose-response to 3 months of quercetin-containing supplements on metabolite and
      quercetin conjugate profile in adults.
AB  - Quercetin, a flavonol in fruits and vegetables, has been demonstrated to have
      antioxidant, anti-inflammatory and immunomodulating influences. The purpose of
      the present study was to determine if quercetin, vitamin C and niacin supplements
      (Q-500 = 500 mg/d of quercetin, 125 mg/d of vitamin C and 5 mg/d of niacin; Q
      1000 = 1000 mg/d of quercetin, 250 mg/d of vitamin C and 10 mg/d of niacin) would
      alter small-molecule metabolite profiles and serum quercetin conjugate levels in
      adults. Healthy adults (fifty-eight women and forty-two men; aged 40-83 years)
      were assigned using a randomised double-blinded placebo-controlled trial to one
      of three supplement groups (Q-1000, Q-500 or placebo). Overnight fasted blood
      samples were collected at 0, 1 and 3 months. Quercetin conjugate concentrations
      were measured using ultra-performance liquid chromatography (UPLC)-MS/MS, and
      metabolite profiles were measured using two MS platforms (UPLC-quadrupole time-of
      flight MS (TOFMS) and GC-TOFMS). Statistical procedures included partial least
      square discriminant analysis (PLS-DA) and linear mixed model analysis with
      repeated measures. After accounting for age, sex and BMI, quercetin
      supplementation was associated with significant shifts in 163
      metabolites/quercetin conjugates (false discovery rate, P<0.05). The top five
      metabolite shifts were an increase in serum guaiacol, 2-oxo-4-methylthiobutanoic
      acid, allocystathionine and two bile acids. Inflammatory and oxidative stress
      metabolites were not affected. PLS-DA revealed a clear separation only between
      the 1000 mg/d and placebo groups (Q(2)Y = 0.763). The quercetin conjugate,
      isorhamnetin-3-glucuronide, had the highest concentration at 3 months followed by
      quercetin-3-glucuronide, quercetin-3-sulphate and quercetin diglucuronide. In
      human subjects, long-term quercetin supplementation exerts disparate and wide
      ranging metabolic effects and changes in quercetin conjugate concentrations.
      Metabolic shifts were apparent at the 1000 mg/d dose; further research is
      required to understand the health implications of these shifts.

PMID- 23151342
TI  - Hypoxia induces myocardial regeneration in zebrafish.
AB  - BACKGROUND: Hypoxia plays an important role in many biological/pathological
      processes. In particular, hypoxia is associated with cardiac ischemia. which,
      although initially inducing a protective response, will ultimately lead to the
      death of cardiomyocytes and loss of tissue, severely affecting cardiac
      functionality. Although myocardial damage/loss remains an insurmountable problem
      for adult mammals, the same is not true for adult zebrafish, which are able to
      completely regenerate their heart after extensive injury. Myocardial regeneration
      in zebrafish involves the dedifferentiation and proliferation of cardiomyocytes
      to replace the damaged/missing tissue; at present, however, little is known about
      what factors regulate this process. METHODS AND RESULTS: We surmised that
      ventricular amputation would lead to hypoxia induction in the myocardium of
      zebrafish and that this may play a role in regulating the regeneration of the
      missing cardiac tissue. Using a combination of O(2) perturbation, conditional
      transgenics, in vitro cell culture, and microarray analysis, we found that
      hypoxia induces cardiomyocytes to dedifferentiate and proliferate during heart
      regeneration in zebrafish and have identified a number of genes that could play a
      role in this process. CONCLUSION: These results indicate that hypoxia plays a
      positive role during heart regeneration, which should be taken into account in
      future strategies aimed at inducing heart regeneration in humans.

PMID- 23151343
TI  - CKIP-1 inhibits cardiac hypertrophy by regulating class II histone deacetylase
      phosphorylation through recruiting PP2A.
AB  - BACKGROUND: Sustained cardiac pressure overload-induced hypertrophy and
      pathological remodeling frequently leads to heart failure. Casein kinase-2
      interacting protein-1 (CKIP-1) has been identified to be an important regulator
      of cell proliferation, differentiation, and apoptosis. However, the physiological
      role of CKIP-1 in the heart is unknown. METHODS AND RESULTS: The results of
      echocardiography and histology demonstrate that CKIP-1-deficient mice exhibit
      spontaneous cardiac hypertrophy with aging and hypersensitivity to pressure
      overload-induced pathological cardiac hypertrophy, as well. Transgenic mice with
      cardiac-specific overexpression of CKIP-1 showed resistance to cardiac
      hypertrophy in response to pressure overload. The results of GST pull-down and
      coimmunoprecipitation assays showed the interaction between CKIP-1 and histone
      deacetylase 4 (HDAC4), through which they synergistically inhibited
      transcriptional activity of myocyte-specific enhancer factor 2C. By directly
      interacting with the catalytic subunit of phosphatase 2A, CKIP-1 overexpression
      enhanced the binding of catalytic subunit of phosphatase-2A to HDAC4 and promoted
      HDAC4 dephosphorylation. CONCLUSIONS: CKIP-1 was found to be an inhibitor of
      cardiac hypertrophy by upregulating the dephosphorylation of HDAC4 through the
      recruitment of protein phosphatase 2A. These results demonstrated a unique
      function of CKIP-1, by which it suppresses cardiac hypertrophy through its
      capacity to regulate HDAC4 dephosphorylation and fetal cardiac genes expression.

PMID- 23151344
TI  - Body mass index and risk of incident hypertension over the life course: the Johns
      Hopkins Precursors Study.
AB  - BACKGROUND: The obesity-hypertension link over the life course has not been well
      characterized, although the prevalence of obesity and hypertension is increasing
      in the United States. METHODS AND RESULTS: We studied the association of body
      mass index (BMI) in young adulthood, into middle age, and through late life with
      risk of developing hypertension in 1132 white men of The Johns Hopkins Precursors
      Study, a prospective cohort study. Over a median follow-up period of 46 years,
      508 men developed hypertension. Obesity (BMI >=30 kg/m(2)) in young adulthood was
      strongly associated with incident hypertension (hazard ratio, 4.17; 95%
      confidence interval, 2.34-7.42). Overweight (BMI 25 to <30 kg/m(2)) also signaled
      increased risk (hazard ratio, 1.58; 95% confidence interval, 1.28-1.96). Men of
      normal weight at age 25 years who became overweight or obese at age 45 years were
      at increased risk compared with men of normal weight at both times (hazard ratio,
      1.57; 95% confidence interval, 1.20-2.07), but not men who were overweight or
      obese at age 25 years who returned to normal weight at age 45 years (hazard
      ratio, 0.91; 95% confidence interval, 0.43-1.92). After adjustment for time
      dependent number of cigarettes smoked, cups of coffee taken, alcohol intake,
      physical activity, parental premature hypertension, and baseline BMI, the rate of
      change in BMI over the life course increased the risk of incident hypertension in
      a dose-response fashion, with the highest risk among men with the greatest
      increase in BMI (hazard ratio, 2.52; 95% confidence interval, 1.82-3.49).
      CONCLUSIONS: Our findings underscore the importance of higher weight and weight
      gain in increasing the risk of hypertension from young adulthood through middle
      age and into late life.

PMID- 23151345
TI  - Incidence, predisposing factors, management and survival following cardiac arrest
      due to subarachnoid haemorrhage: a review of the literature.
AB  - INTRODUCTION: The prevalence of cardiac arrest among patients with subarachnoid
      haemorrhage [SAH], and the prevalence of SAH as the cause following out-of
      hospital cardiac arrest [OHCA] or in-hospital cardiac arrest [IHCA] is unknown.
      In addition it is unclear whether cardiopulmonary resuscitation [CPR] and post
      resuscitation care management differs, and to what extent this will lead to
      meaningful survival following cardiac arrest [CA] due to SAH. AIM: We reviewed
      the literature in order to describe; 1.The prevalence and predisposing factors of
      CA among patients with SAH 2.The prevalence of SAH as the cause of OHCA or IHCA
      and factors characterising CPR 3.The survival and management of SAH patients with
      CA. MATERIAL AND METHODS: The following sources, PubMed, CinAHL and The Cochrane
      DataBase were searched using the following Medical Subheadings [MeSH]; 1. OHCA,
      IHCA, heart arrest and 2. subarachnoid haemorrhage. Articles containing relevant
      data based on the abstract were reviewed in order to find results relevant to the
      proposed research questions. Manuscripts in other languages than English, animal
      studies, reviews and case reports were excluded. RESULTS: A total of 119
      publications were screened for relevance and 13 papers were included. The
      prevalence of cardiac or respiratory arrest among all patients with SAH is
      between 3-11%, these patients commonly have a severe SAH with coma, large bleeds
      and evidence of raised intracerebral pressure on computed tomography scans
      compared to those who did not experience a CA. The prevalence of patients with
      SAH as the cause of the arrest among OHCA cases vary between 4 to 8% among those
      who die before hospital admission, and between 4 to 18% among those who are
      admitted. The prevalence of SAH as the cause following IHCA is low, around 0.5%
      according to one recent study. In patients with OHCA survival to hospital
      discharge is poor with 0 to 2% surviving. The initial rhythm is commonly asystole
      or pulseless electrical tachycardia. In IHCA the survival rate is variable with 0
      27% surviving. All survivors experience brief cardiac arrests with short
      latencies to ROSC. CONCLUSION: Cardiac arrest is a fairly common complication
      following severe SAH and these patients are encountered both in the pre-hospital
      and in-hospital setting. Survival is possible if the arrest occurs in the
      hospital and the latency to ROSC is short. In OHCA the outcome seems to be
      uniformly poor despite initially successful resuscitation.

PMID- 23151346
TI  - GmDREB2A;2, a canonical DEHYDRATION-RESPONSIVE ELEMENT-BINDING PROTEIN2-type
      transcription factor in soybean, is posttranslationally regulated and mediates
      dehydration-responsive element-dependent gene expression.
AB  - Soybean (Glycine max) is an important crop around the world. Abiotic stress
      conditions, such as drought and heat, adversely affect its survival, growth, and
      production. The DEHYDRATION-RESPONSIVE ELEMENT-BINDING PROTEIN2 (DREB2) group
      includes transcription factors that contribute to drought and heat stress
      tolerance by activating transcription through the cis-element dehydration
      responsive element (DRE) in response to these stress stimuli. Two modes of
      regulation, transcriptional and posttranslational, are important for the
      activation of gene expression by DREB2A in Arabidopsis (Arabidopsis thaliana).
      However, the regulatory system of DREB2 in soybean is not clear. We identified a
      new soybean DREB2 gene, GmDREB2A;2, that was highly induced not only by
      dehydration and heat but also by low temperature. GmDREB2A;2 exhibited a high
      transactivation activity via DRE and has a serine/threonine-rich region, which
      corresponds to a negative regulatory domain of DREB2A that is involved in its
      posttranslational regulation, including destabilization. Despite the partial
      similarity between these sequences, the activity and stability of the GmDREB2A;2
      protein were enhanced by removal of the serine/threonine-rich region in both
      Arabidopsis and soybean protoplasts, suggestive of a conserved regulatory
      mechanism that involves the recognition of serine/threonine-rich sequences with a
      specific pattern. The heterologous expression of GmDREB2A;2 in Arabidopsis
      induced DRE-regulated stress-inducible genes and improved stress tolerance.
      However, there were variations in the growth phenotypes of the transgenic
      Arabidopsis, the induced genes, and their induction ratios between GmDREB2A;2 and
      DREB2A. Therefore, the basic function and regulatory machinery of DREB2 have been
      maintained between Arabidopsis and soybean, although differentiation has also
      occurred.

PMID- 23151349
TI  - Application of cathodoluminescence microscopy and spectroscopy in geosciences.
AB  - Cathodoluminescence (CL) microscopy and spectroscopy are luminescence techniques
      with widespread applications in geosciences. Many rock-forming and accessory
      minerals show CL characteristics, which can be successfully used in geoscientific
      research. One of the most spectacular applications is the visualization of growth
      textures and other internal structures that are not discernable with other
      analytical techniques. In addition, information from CL imaging and spectroscopy
      can be used for the reconstruction of processes of mineral formation and
      alteration to provide information about the real structure of minerals and
      materials, and to prove the presence and type of lattice incorporation of several
      trace elements. In the present article, an overview about CL properties of
      selected minerals is given, and several examples of applications discussed. The
      presented data illustrate that best results are achieved when luminescence
      studies are performed under standardized conditions and combined with other
      analytical techniques with high sensitivity and high spatial resolution.

PMID- 23151348
TI  - Thioredoxin m4 controls photosynthetic alternative electron pathways in
      Arabidopsis.
AB  - In addition to the linear electron flow, a cyclic electron flow (CEF) around
      photosystem I occurs in chloroplasts. In CEF, electrons flow back from the donor
      site of photosystem I to the plastoquinone pool via two main routes: one that
      involves the Proton Gradient Regulation5 (PGR5)/PGRL1 complex (PGR) and one that
      is dependent of the NADH dehydrogenase-like complex. While the importance of CEF
      in photosynthesis and photoprotection has been clearly established, little is
      known about its regulation. We worked on the assumption of a redox regulation and
      surveyed the putative role of chloroplastic thioredoxins (TRX). Using Arabidopsis
      (Arabidopsis thaliana) mutants lacking different TRX isoforms, we demonstrated in
      vivo that TRXm4 specifically plays a role in the down-regulation of the NADH
      dehydrogenase-like complex-dependent plastoquinone reduction pathway. This result
      was confirmed in tobacco (Nicotiana tabacum) plants overexpressing the TRXm4
      orthologous gene. In vitro assays performed with isolated chloroplasts and
      purified TRXm4 indicated that TRXm4 negatively controls the PGR pathway as well.
      The physiological significance of this regulation was investigated under steady
      state photosynthesis and in the pgr5 mutant background. Lack of TRXm4 reversed
      the growth phenotype of the pgr5 mutant, but it did not compensate for the
      impaired photosynthesis and photoinhibition sensitivity. This suggests that the
      physiological role of TRXm4 occurs in vivo via a mechanism distinct from direct
      up-regulation of CEF.

PMID- 23151347
TI  - The impact of global change factors on redox signaling underpinning stress
      tolerance.

PMID- 23151350
TI  - Spanish versions of the 6-item carpal tunnel syndrome symptoms scale (CTS-6) and
      palmar pain scale.

PMID- 23151351
TI  - The proximal first dorsal metacarpal artery free flap for reconstruction of
      complex digital defects.
AB  - We describe our experience and outcome with the 'Proximal first dorsal metacarpal
      artery free flap'. Ten consecutive cases utilizing the proximal first dorsal
      metacarpal artery free flap for complex digital defects were studied. Surgical
      technique, patient demographics, and flap outcome data were collected. Patient
      satisfaction was analysed using a questionnaire. All defects healed successfully
      with no loss of free flaps. The short-pedicle proximal first dorsal metacarpal
      artery free flap enables primary closure of the donor site up to 2 cm of width
      (in nine of the ten donor sites). The flap is a reliable and versatile
      alternative in selected cases of complex digital injuries.

PMID- 23151352
TI  - Surgical treatment of primary Dupuytren's contractures of the fingers in the UK:
      surgeons' preferences and research priorities.

PMID- 23151354
TI  - Kiwifruit consumption favourably affects plasma lipids in a randomised controlled
      trial in hypercholesterolaemic men.
AB  - The unique composition of green kiwifruit has the potential to benefit CVD risk.
      The aim of the present study was to investigate the effect of consuming two green
      kiwifruits daily in conjunction with a healthy diet on plasma lipids and other
      metabolic markers and to examine response according to APOE genotype in
      hypercholesterolaemic men. After undergoing a 4-week healthy diet, eighty-five
      hypercholesterolaemic men (LDL-cholesterol (LDL-C) > 3.0 mmol/l and TAG < 3
      mmol/l) completed an 8-week randomised controlled cross-over study of two 4-week
      intervention sequences of two green kiwifruits per d plus healthy diet
      (intervention) or healthy diet alone (control). Anthropometric measures, blood
      pressure (BP) and fasting blood samples (plasma lipids, serum apoA1 and apoB,
      insulin, glucose, high-sensitivity C-reactive protein (hs-CRP)) were taken at
      baseline, and at 4 and 8 weeks. After the kiwifruit intervention, plasma HDL
      cholesterol (HDL-C) concentrations were significantly higher (mean difference
      0.04; 95% CI 0.01, 0.07 mmol/l; P = 0.004) and the total cholesterol (TC):HDL-C
      ratio was significantly lower (mean difference 20.5; 95% CI 20.24, 20.05 mmol/l;
      P = 0.002) compared with the control. In carriers of the APOE4 allele, TAG
      decreased significantly (mean difference -0.18; 95% CI -0.34, -0.02 mol/l; P =
      0.03) with kiwifruit compared with control. There were no significant differences
      between the two interventions for plasma TC, LDL-C, insulin, glucose, hs-CRP and
      BP. The small but significant increase in HDL-C and decrease in TC:HDL-C ratio
      and TAG (in APOE4 carriers) suggest that the regular inclusion of green kiwifruit
      as part of a healthy diet may be beneficial in improving the lipid profiles of
      men with high cholesterol.

PMID- 23151355
TI  - Amantadine and the place of acupuncture in the treatment of fatigue in patients
      with multiple sclerosis: an observational study.
AB  - BACKGROUND: Fatigue is a common symptom in patients with multiple sclerosis (MS).
      It has significant negative effects on the quality of life of patients with the
      condition. There are few therapeutic modalities for fatigue, which are also
      usually not sufficiently effective. The aim of this study was to evaluate the
      efficacy of acupuncture on this common symptom of patients with MS. METHODS: In
      this before-and-after clinical trial, 40 patients with definite diagnoses of MS,
      according to the 'McDonald' criteria, were studied. Patients who had Expanded
      Disability Status Scale (EDSS) scores greater than 4, or who had another disease
      that could be potentially responsible for their fatigue, were excluded from the
      study. In all, 20 patients with fatigue refractory to amantadine underwent 12
      sessions of acupuncture. Fatigue was scored according to the Fatigue Severity
      Scale (FSS). RESULTS: A total of 15 (37.5%) patients with MS with fatigue
      responded to amantadine. The mean FSS score reduction after 2 months of treatment
      was 8+/-4, which was statistically significant (p<0.001). Of the 20 patients who
      were resistant to amantadine, 5 (25%) responded to acupuncture combined with
      amantadine treatment. The FSS scores of the 20 patients who were refractory were
      significantly reduced after this treatment (mean: 13+/-6, p<0.001). CONCLUSIONS:
      Acupuncture appears to be associated with benefits for a proportion of patients
      with fatigue who are resistant to conventional drugs such as amantadine, and this
      finding justifies further research.

PMID- 23151353
TI  - Completion of the swine genome will simplify the production of swine as a large
      animal biomedical model.
AB  - BACKGROUND: Anatomic and physiological similarities to the human make swine an
      excellent large animal model for human health and disease. METHODS: Cloning from
      a modified somatic cell, which can be determined in cells prior to making the
      animal, is the only method available for the production of targeted modifications
      in swine. RESULTS: Since some strains of swine are similar in size to humans,
      technologies that have been developed for swine can be readily adapted to humans
      and vice versa. Here the importance of swine as a biomedical model, current
      technologies to produce genetically enhanced swine, current biomedical models,
      and how the completion of the swine genome will promote swine as a biomedical
      model are discussed. CONCLUSIONS: The completion of the swine genome will enhance
      the continued use and development of swine as models of human health, syndromes
      and conditions.

PMID- 23151356
TI  - Socially responsible genetic research with descendants of the First Australians.
AB  - Aboriginal Australians, one of the world's indigenous peoples now outnumbered
      through colonization, are the most under-represented in genetic research because
      they feel that the benefits do not outweigh the social cost of involvement.
      Descendants of the First Australians have survived a period of European
      occupation during which time they were dispossessed of land, language and
      cultural identity resulting in inequities in health, education, and employment
      opportunities. Compared to Maori and Native American peoples, the ability to form
      organizations that help to control their affairs is very recent. The desire to
      control is understandably strong yet the 'gate-keeping' role of some
      organizations risks shifting the control away from smaller communities and has
      become increasingly politicized. In the past, research practices by Western
      scientists were poorly presented and have resulted in resistance to proposals
      that are perceived to have no beneficial outcomes for participants. In this age
      of advanced technological expertise in genetics, benefits to all humanity are
      clear to those carrying out research projects, yet not always to those being
      asked to participate, presenting extra challenges. Excellent guidelines for
      ethical conduct in research are available to assist researchers, prospective
      participants, and ethics committees or review boards that approve and monitor
      procedures. The essence of these guidelines are that research should be carried
      out with a spirit of integrity, respect, reciprocity, parity, recognition of
      survival and protection of social and cultural values, a need for control and
      shared responsibility. Specific Aboriginal organizations, with which researchers
      need to work to negotiate partnerships, vary within and between Australian states
      and will always expect Aboriginal personnel to be involved. People experienced in
      the consultation process are necessary as part of a team. By working patiently
      through lengthy negotiations with Aboriginal Australians, scientists can achieve
      valuable results, but failure to do so with respect and understanding will not
      yield hoped for outcomes. My own experience working with communities in the
      Darling River region of western New South Wales has been an enriching and
      rewarding one, with a long period of successful research lately delayed by
      increased expectation of monitoring and involvement at state level.

PMID- 23151357
TI  - Contrasts between the effects of zinc-alpha2-glycoprotein, a putative beta3/2
      adrenoceptor agonist and the beta3/2-adrenoceptor agonist BRL35135 in C57Bl/6
      (ob/ob) mice.
AB  - Previous studies by Tisdale et al. have reported that zinc-alpha(2)-glycoprotein
      (ZAG (AZGP1)) reduces body fat content and improves glucose homeostasis and the
      plasma lipid profile in Aston (ob/ob) mice. It has been suggested that this might
      be mediated via agonism of beta(3)- and possibly beta(2)-adrenoceptors. We
      compared the effects of dosing recombinant human ZAG (100 MUg, i.v.) and BRL35135
      (0.5 mg/kg, i.p.), which is in rodents a 20-fold selective beta(3)- relative to
      beta(2)-adrenoceptor agonist, given once daily for 10 days to male C57Bl/6
      Lep(ob)/Lep(ob) mice. ZAG, but not BRL35135, reduced food intake. BRL35135, but
      not ZAG, increased energy expenditure acutely and after sub-chronic
      administration. Only BRL35135 increased plasma concentrations of glycerol and non
      esterified fatty acid. Sub-chronic treatment with both ZAG and BRL35135 reduced
      fasting blood glucose and improved glucose tolerance, but the plasma insulin
      concentration 30 min after administration of glucose was lowered only by
      BRL35135. Both ZAG and BRL35135 reduced beta(1)-adrenoceptor mRNA levels in white
      adipose tissue, but only BRL35135 reduced beta(2)-adrenoceptor mRNA. Both ZAG and
      BRL35135 reduced beta(1)-adrenoceptor mRNA levels in brown adipose tissue, but
      neither influenced beta(2)-adrenoceptor mRNA, and only BRL35135 increased beta(3)
      adrenoceptor and uncoupling protein-1 (UCP1) mRNA levels in brown adipose tissue.
      Thus, ZAG and BRL35135 had similar effects on glycaemic control and shared some
      effects on beta-adrenoceptor gene expression in adipose tissue, but ZAG did not
      display the thermogenic effects of the beta-adrenoceptor agonist, nor did it
      increase beta(3)-adrenoceptor or UCP1 gene expression in brown adipose tissue.
      ZAG does not behave as a typical beta(3/2)-adrenoceptor agonist.

PMID- 23151358
TI  - The lipocalin-type prostaglandin D2 synthase knockout mouse model of insulin
      resistance and obesity demonstrates early hypothalamic-pituitary-adrenal axis
      hyperactivity.
AB  - Obesity and diabetes are closely associated with hyperactivation of the
      hypothalamic-pituitary-adrenal (HPA) axis. In this study, the diet-induced obese
      C57BL/6 mouse was used to test the hypothesis that chronically elevated metabolic
      parameters associated with the development of obesity such as cholesterol and
      glucose can aggravate basal HPA axis activity. Because the lipocalin-type
      prostaglandin D(2) synthase (L-PGDS) knockout (KO) mouse is a model of
      accelerated insulin resistance, glucose intolerance, and obesity, it was further
      hypothesized that HPA activity would be greater in this model. Starting at 8
      weeks of age, the L-PGDS KO and C57BL/6 mice were maintained on a low-fat or high
      fat diet. After 20 or 37 weeks, fasting metabolic parameters and basal HPA axis
      hormones were measured and compared between genotypes. Correlation analyses were
      performed to identify associations between obesity-related chronic metabolic
      changes and changes in the basal activity of the HPA axis. Our results have
      identified strong positive correlations between total cholesterol, LDL
      cholesterol, glucose, and HPA axis hormones that increase with age in the C57BL/6
      mice. These data confirm that obesity-related elevations in cholesterol and
      glucose can heighten basal HPA activity. Additionally, the L-PGDS KO mice show
      early elevations in HPA activity with no age-related changes relative to the
      C57BL/6 mice.

PMID- 23151359
TI  - Thyroid hormone regulation of Sirtuin 1 expression and implications to integrated
      responses in fasted mice.
AB  - Sirtuin 1 (SIRT1), a NAD(+)-dependent deacetylase, has been connected to
      beneficial effects elicited by calorie restriction. Physiological adaptation to
      starvation requires higher activity of SIRT1 and also the suppression of thyroid
      hormone (TH) action to achieve energy conservation. Here, we tested the
      hypothesis that those two events are correlated and that TH may be a regulator of
      SIRT1 expression. Forty-eight-hour fasting mice exhibited reduced serum TH and
      increased SIRT1 protein content in liver and brown adipose tissue (BAT), and
      physiological thyroxine replacement prevented or attenuated the increment of
      SIRT1 in liver and BAT of fasted mice. Hypothyroid mice exhibited increased liver
      SIRT1 protein, while hyperthyroid ones showed decreased SIRT1 in liver and BAT.
      In the liver, decreased protein is accompanied by reduced SIRT1 activity and no
      alteration in its mRNA. Hyperthyroid and hypothyroid mice exhibited increases and
      decreases in food intake and body weight gain respectively. Food-restricted
      hyperthyroid animals (pair-fed to euthyroid group) exhibited liver and BAT SIRT1
      protein levels intermediary between euthyroid and hyperthyroid mice fed ad
      libitum. Mice with TH resistance at the liver presented increased hepatic SIRT1
      protein and activity, with no alteration in Sirt1 mRNA. These results suggest
      that TH decreases SIRT1 protein, directly and indirectly, via food ingestion
      control and, in the liver, this reduction involves TRbeta. The SIRT1 reduction
      induced by TH has important implication to integrated metabolic responses to
      fasting, as the increase in SIRT1 protein requires the fasting-associated
      suppression of TH serum levels.

PMID- 23151361
TI  - Investigation of the mechanisms contributing to the compensatory increase in
      insulin secretion during dexamethasone-induced insulin resistance in rhesus
      macaques.
AB  - Dexamethasone has well-described effects to induce insulin resistance and
      increase insulin secretion. Herein, we examined potential contributors to the
      effect of dexamethasone to increase insulin secretion in rhesus macaques. Six
      male rhesus macaques received daily injections of either saline or dexamethasone
      (0.25 mg/kg i.m. for 7 days) in random order with 3 weeks between treatments. At
      the end of the treatment period, animals were fasted overnight and underwent a
      feeding study the next day, during which blood samples were taken before and for
      60 min after a meal in order to assess islet hormone and incretin secretion.
      Dexamethasone induced marked increases in fasting plasma insulin, glucagon,
      leptin, and adiponectin concentrations (P<0.05). Surprisingly, the glycemic
      response after meal ingestion was decreased twofold during dexamethasone
      treatment (P<0.05). Dexamethasone-treated animals exhibited a significant
      increase in both insulin and glucose-dependent insulinotropic polypeptide (GIP)
      secretion during the feeding study (P<0.05). However, glucagon-like peptide-1
      secretion was significantly lower in dexamethasone-treated animals compared with
      controls (P<0.01). Fasting and meal-stimulated pancreatic polypeptide
      concentrations (an index of the parasympathetic input to the islet) did not
      differ between saline and dexamethasone treatments. However, the
      proinsulin:insulin ratio was decreased throughout the feeding study with
      dexamethasone treatment suggesting an improvement of beta-cell function (P<0.05).
      In conclusion, the maintenance of euglycemia and reduction of postprandial
      glycemia with short-term dexamethasone treatment appears to be due to the marked
      elevations of fasting and meal-stimulated insulin secretion. Furthermore,
      increases in postprandial GIP secretion with dexamethasone treatment appear to
      contribute to the effect of dexamethasone treatment to increase insulin
      secretion.

PMID- 23151360
TI  - Poor pubertal protein nutrition disturbs glucose-induced insulin secretion
      process in pancreatic islets and programs rats in adulthood to increase fat
      accumulation.
AB  - Similar to gestation/lactation, puberty is also a critical phase in which
      neuronal connections are still being produced and during which metabolic changes
      may occur if nutrition is disturbed. In the present study we aimed to determine
      whether peripubertal protein restriction induces metabolic programming. Thirty
      day-old male rats were fed either a low protein (LP group) diet (4% w/w protein)
      or a normal protein (NP group) diet (23%) until 60 days of age, when they
      received the NP diet until they were 120 days old. Body weight (BW), food intake,
      fat tissue accumulation, glucose tolerance, and insulin secretion were evaluated.
      The nerve electrical activity was recorded to evaluate autonomous nervous system
      (ANS) function. Adolescent LP rats presented hypophagia and lower BW gain during
      the LP diet treatment (P<0.001). However, the food intake and BW gain by the LP
      rats were increased (P<0.001) after the NP diet was resumed. The LP rats
      presented mild hyperglycemia, hyperinsulinemia, severe hyperleptinemia upon
      fasting, peripheral insulin resistance and increased fat tissue accumulation and
      vagus nerve activity (P<0.05). Glucose-induced insulin secretion was greater in
      the LP islets than in the NP islets; however, the cholinergic response was
      decreased (P<0.05). Compared with the islets from the NP rats, the LP islets
      showed changes in the activity of muscarinic receptors (P<0.05); in addition, the
      inhibition of glucose-induced insulin secretion by epinephrine was attenuated
      (P<0.001). Protein restriction during adolescence caused high-fat tissue
      accumulation in adult rats. Islet dysfunction could be related to an ANS
      imbalance.

PMID- 23151362
TI  - Preliminary study of online machine translation use of nursing literature:
      quality evaluation and perceived usability.
AB  - BACKGROUND: Japanese nurses are increasingly required to read published
      international research in clinical, educational, and research settings. Language
      barriers are a significant obstacle, and online machine translation (MT) is a
      tool that can be used to address this issue. We examined the quality of Google
      Translate(r) (English to Japanese and Korean to Japanese), which is a
      representative online MT, using a previously verified evaluation method. We also
      examined the perceived usability and current use of online MT among Japanese
      nurses. FINDINGS: Randomly selected nursing abstracts were translated and then
      evaluated for intelligibility and usability by 28 participants, including
      assistants and research associates from nursing universities throughout Japan.
      They answered a questionnaire about their online MT use. From simple comparison
      of mean scores between two language pairs, translation quality was significantly
      better, with respect to both intelligibility and usability, for Korean-Japanese
      than for English-Japanese. Most respondents perceived a language barrier. Online
      MT had been used by 61% of the respondents and was perceived as not useful
      enough. CONCLUSION: Nursing articles translated from Korean into Japanese by an
      online MT system could be read at an acceptable level of comprehension, but the
      same could not be said for English-Japanese translations. Respondents with
      experience using online MT used it largely to grasp the overall meanings of the
      original text. Enrichment in technical terms appeared to be the key to better
      usability. Users will be better able to use MT outputs if they improve their
      foreign language proficiency as much as possible. Further research is being
      conducted with a larger sample size and detailed analysis.

PMID- 23151363
TI  - Dietary fish oil reduces glomerular injury and elevated renal
      hydroxyeicosatetraenoic acid levels in the JCR:LA-cp rat, a model of the
      metabolic syndrome.
AB  - We have previously shown nutritional intervention with fish oil (n-3 PUFA) to
      reduce numerous complications associated with the metabolic syndrome (MetS) in
      the JCR:LA-corpulent (cp) rat. In the present study, we sought to explore the
      potential role of fish oil to prevent glomerulosclerosis in JCR:LA-cp rats via
      renal eicosanoid metabolism and lipidomic analysis. Male lean and MetS JCR:LA-cp
      rats were fed a lipid-balanced diet supplemented with fish oil (5 or 10 % of
      total fat). After 16 weeks of feeding, albuminuria was significantly reduced in
      MetS rats supplemented with 5 or 10 % fish oil ( - 53 and - 70 %, respectively,
      compared with the untreated MetS rats). The 5 % fish oil diet resulted in
      markedly lower glomerulosclerosis ( - 43 %) in MetS rats and to a lesser extent
      in those supplemented with 10 % fish oil. Interestingly, untreated MetS rats had
      higher levels of 11- and 12-hydroxyeicosatetraenoic acids (HETE) v. lean rats.
      Dietary fish oil reduced these levels, as well as other (5-, 9- and 15-) HETE.
      Whilst genotype did not alter prostanoid levels, fish oil reduced endogenous
      renal levels of 6-keto PGF1alpha (PGI2 metabolite), thromboxane B2 (TxB2),
      PGF2alpha and PGD2 by approximately 60 % in rats fed 10 % fish oil, and TxB2 ( -
      50 %) and PGF2alpha ( - 41 %) in rats fed 5 % fish oil. In conclusion, dietary
      fish oil prevented glomerular damage in MetS rats and mitigated the elevation in
      renal HETE levels. These results suggest a potential role for dietary fish oil to
      improve dysfunctional renal eicosanoid metabolism associated with kidney damage
      during conditions of the MetS.

PMID- 23151364
TI  - The effect of distance to formal health facility on childhood mortality in rural
      Tanzania, 2005-2007.
AB  - BACKGROUND: Major improvements are required in the coverage and quality of
      essential childhood interventions to achieve Millennium Development Goal Four
      (MDG 4). Long distance to health facilities is one of the known barriers to
      access. We investigated the effect of networked and Euclidean distances from home
      to formal health facilities on childhood mortality in rural Tanzania between 2005
      and 2007. METHODS: A secondary analysis of data from a cohort of 28,823 children
      younger than age 5 between 2005 and 2007 from Ifakara Health and Demographic
      Surveillance System was carried out. Both Euclidean and networked distances from
      the household to the nearest health facility were calculated using geographical
      information system methods. Cox proportional hazard regression models were used
      to investigate the effect of distance from home to the nearest health facility on
      child mortality. RESULTS: Children who lived in homes with networked distance>5
      km experienced approximately 17% increased mortality risk (HR=1.17; 95% CI 1.02
      1.38) compared to those who lived <5 km networked distance to the nearest health
      facility. Death of a mother (HR=5.87; 95% CI 4.11-8.40), death of preceding
      sibling (HR=1.9; 95% CI 1.37-2.65), and twin birth (HR=2.9; 95% CI 2.27-3.74)
      were the strongest independent predictors of child mortality. CONCLUSIONS:
      Physical access to health facilities is a determinant of child mortality in rural
      Tanzania. Innovations to improve access to health facilities coupled with birth
      spacing and care at birth are needed to reduce child deaths in rural Tanzania.

PMID- 23151365
TI  - Accuracy of regional cerebral oxygen saturation in predicting postoperative
      cognitive dysfunction after total hip arthroplasty: regional cerebral oxygen
      saturation predicts POCD.
AB  - To estimate the accuracy of regional cerebral oxygen saturation (rSO(2)) in
      predicting postoperative cognitive dysfunction (POCD) for patients undergoing
      total hip arthroplasty, 46 patients aged more than 50years old were enrolled. We
      measured the patients' cognitive function by using a battery of six
      neuropsychological tests before surgery and then 7days after surgery again.
      rSO(2) was continuously monitored by near-infrared spectroscopy during surgery.
      POCD was present in 9 (19.6%) patients 1week after surgery. Logistic regression
      analysis showed that increasing age [OR=1.224, P=0.035] and maximum percentage
      drop in rSO(2) (rSO(2%max)) [OR=1.618, P=0.011] were significant risk factors for
      POCD. The area under the receiver operating characteristic curve of rSO(2%max)
      was 0.833 [95% confidence interval (CI) 0.615-1.051] at cutoff value of 11%. The
      specificity and sensitivity of rSO(2%max) >11% in predicting POCD were 77.8% and
      86.5%, respectively. rSO(2%max) more than 11% was a potential predictor for POCD.

PMID- 23151366
TI  - Unsatisfactory accuracy as determined by computer navigation of VISIONAIRE
      patient-specific instrumentation for total knee arthroplasty.
AB  - This investigation evaluated the Smith and Nephew VISIONAIRE patient-specific
      cutting block (PSCB) system for total knee arthroplasty. A consecutive series of
      60 patients was recruited. Intraoperative computer navigation was used to
      evaluate the accuracy of the cutting blocks in the coronal and sagittal planes
      for the tibia, as well as rotational plane for the femur. The PSCB would have
      placed 79.3% of the sample within +/-3 degrees  of the preoperative plan in the
      coronal plane, while the rotational and sagittal alignment results within +/-3
      degrees  were 77.2% and 54.5% respectively. The VISIONAIRE PSCB system achieved
      unacceptable accuracy when assessed by computer navigation. There might be many
      sources of error, but caution is recommended before using this system routinely
      without objective verification of alignment.

PMID- 23151367
TI  - Stair ascending and descending in hip resurfacing and large head total hip
      arthroplasty patients.
AB  - Large head total hip arthroplasty (THA) and hip resurfacing arthroplasty (HRA)
      are alternatives to standard THA that generally have head sizes larger than 36mm.
      This study examined 20 patients (10 large head THA and 10 HRA), at an average of
      18months postoperatively, and 15 healthy control subjects during stair
      negotiation. Hip kinetic and kinematic variables and ground reaction forces were
      measured. The THA and HRA groups ascended the stairs with increased peak hip
      flexion angles and decreased hip extension angles as compared with controls. The
      operative groups also descended the stairs with decreased hip flexion moments. No
      differences between the operative groups were observed. Eighteen months
      postoperatively, patients with large head THA or HRA display abnormal flexion and
      extension during a physically-demanding task.

PMID- 23151368
TI  - Treatment of prosthetic joint infections: validation of a surgical algorithm and
      proposal of a simplified alternative.
AB  - The Del Pozo and Patel (DPP) algorithm permits to identify suitable candidates
      for debridement and implant retention (DR) in prosthetic joint infections (PJI),
      but does not include gram-negative bacilli (GNB) as a risk factor of worst
      outcome. We conducted a retrospective study to validate the DPP algorithm and
      propose a simplified algorithm including GNB PJI. From 2002 to 2009, 73 PJI
      underwent surgery; 55% were chosen according to PDD algorithm. Non-adherence
      increased the risk of treatment failure (HR = 4.2). Performing DR in the presence
      of GNB PJI and performing DR in a joint prosthesis implanted for >3 months
      without hematogenous infection were independent risk factors. Our simplified
      algorithm, based on these 2 criteria, showed comparable performance to the DPP
      algorithm but increased eligibility for DR by a 2.4 fold.

PMID- 23151369
TI  - The progress of nations: what we can learn from Taiwan.

PMID- 23151370
TI  - Changing trends in the prevalence of common mental disorders in Taiwan: a 20-year
      repeated cross-sectional survey.
AB  - BACKGROUND: Macrosocial changes might affect mental health. We investigated
      whether the prevalence of common mental disorders (CMDs) changed over a 20-year
      period of industrialisation in Taiwan. METHODS: We used the 12-item Chinese
      Health Questionnaire to assess mental status of Taiwanese adults in 1990, 1995,
      2000, 2005, and 2010. Respondents with scores of 3 or higher were classified as
      having probable CMDs. We assessed trends of probable CMDs with the Cochran
      Armitage test and their risk factors (sex, age, marital status, educational
      level, employment status, and physical health) with multivariable logistic
      regression. The trends were compared with national rates of unemployment,
      divorce, and suicide. FINDINGS: Of 10,548 respondents, 9079 (86.1%) completed
      questionnaires. The prevalence of probable CMDs doubled from 11.5% in 1990 to
      23.8% in 2010 (time trend p<0.001). Increases paralleled rises in national rates
      of unemployment, divorce, and suicide at all five timepoints. Significant risk
      factors for probable CMDs were female sex (adjusted odds ratio 1.6, 95% CI 1.4
      1.8), 6 or fewer years of education (1.3, 1.1-1.5), unemployment (1.4, 1.1-1.7),
      and poor physical health that limited daily activities (6.5, 5.4-8.0). When we
      controlled for these factors in multivariable models, the time trends remained
      significant (p<0.0001). INTERPRETATION: National rates of unemployment, divorce,
      and suicide increased in parallel with prevalence of probable CMDs in Taiwan.
      Therefore, clinical and social preventive measures both seem important during
      times of change to the economy and labour market. FUNDING: Taiwan National
      Science Council.

PMID- 23151371
TI  - 3D ultrasound and Doppler angiography for evaluation of fetal cardiovascular
      anomalies.
AB  - OBJECTIVE: To highlight the value of 3D ultrasound in the prenatal assessment of
      fetal cardiovascular anomalies through offline diagnosis and/or second opinion
      (e.g. via internet link). METHODS: A retrospective offline analysis of volume
      datasets of fetuses diagnosed with cardiovascular anomalies by 2D ultrasound was
      conducted. RESULTS: Thirty-three fetuses with 38 cardiac malformations were
      evaluated. Mean gestational age at diagnosis was 26 weeks (range, 20-34 weeks).
      Isolated cardiovascular malformations were detected in 23 fetuses. Extracardiac
      abnormalities were identified in 8 fetuses, of which 2 had trisomy 21 and 1 had
      trisomy 18. One fetus exhibited 22q11 microdeletion. Ten pregnancy terminations
      were performed. CONCLUSION: Offline analysis of cardiovascular anomalies
      conferred significant diagnostic advantages over 2D ultrasound. 3D ultrasound is
      invaluable for the prenatal diagnosis and management of congenital heart
      diseases. It may be used to facilitate scientific cooperation between high- and
      low-income countries.

PMID- 23151372
TI  - Effects of an extended free-of-fee strategy on the rate of cervical Papanicolaou
      smear screening in Israel.
AB  - OBJECTIVE: To investigate the influence of an extended free-of-fee strategy on
      the rate of cervical Papanicolaou (Pap) smear screening in Israel. METHODS: A
      retrospective analysis was conducted of data obtained from a computer-generated
      list of women aged 15-74 years who attended appointments with Clalit Health
      Services between January 1, 2008, and November 30, 2011, during which Pap smears
      were taken. The basic strategy allowed a no-fee Pap smear once every 3 years
      between the ages of 35 and 54 years; the extended strategy allowed a no-fee Pap
      smear once every 3 years between the ages of 25 and 54 years. RESULTS: In all, 65
      565 Pap smears were taken. The mean monthly study population was 161 438 women.
      The mean monthly Pap smear rate for the basic strategy was 0.64% +/- 0.5% (95%
      confidence interval [CI], 0.59-0.68) versus 0.75% +/- 0.6% (95% CI, 0.70-0.79)
      for the extended strategy (P=0.004). Age group (P<0.001), Pap smear strategy type
      (P<0.001), and combined age group and strategy type (P=0.028) each predicted the
      monthly rate of Pap smear screening in a univariate analysis. CONCLUSION:
      Implementation of the extended free-of-fee strategy increased the rate of Pap
      smear screening among Israeli women.

PMID- 23151374
TI  - Neuroprotective effect of cocaine- and amphetamine-regulated transcript peptide
      in spinal cord injury in mice.
AB  - We explored the effect of cocaine- and amphetamine-regulated transcript peptide
      (CART), alone and in combination with methylprednisolone (MP), on the cellular
      pathology and locomotor recovery of mice following spinal cord injury (SCI).
      While cellular pathology was evaluated in terms of spinal cord histology and
      profile of astrocytes following immunolabeling with antibodies against glial
      fibrillary acidic protein (GFAP), locomotor recovery was monitored using hindlimb
      motor function scoring system. At 24 h post-SCI, there was a massive loss of
      motor function and cysts formation in the spinal cord. The SCI mice, following 3
      days and onwards, showed a significant (P < 0.001) increase in the population and
      hypertrophy of GFAP + astrocytes, suggesting the occurrence of reactive
      astrogliosis. Intra-fourth ventricular administration of CART (54-102) or
      intravenous treatment with MP, dose dependently improved motor function score,
      while CART-antibody (intra-fourth ventricular) was ineffective. This
      neuroprotective effect of MP was potentiated by the subeffective dose of CART and
      antagonized by CART-antibody. CART or MP treatment not only prevented the cysts
      formation, but also significantly attenuated the population of GFAP + astrocytes
      at days 3, 7, 14, 21 and 28 post-SCI and the hypertrophy of astrocytes at day 14
      and 28. The histological consequence of SCI, like cysts formation in the spinal
      cord, was rapidly improved by CART and/or MP. Taken together, the data suggest
      that CART may exert its neuroprotective effect via inhibition of post-SCI
      astrogliosis and participate in the MP mediated neuroprotection.

PMID- 23151373
TI  - Combined chelation therapy with deferasirox and deferoxamine in thalassemia.
AB  - Iron overload is the primary cause of mortality and morbidity in thalassemia
      major despite advances in chelation therapy. We performed a pilot clinical trial
      to evaluate the safety and efficacy of combined therapy with deferasirox (DFX, 20
      30 mg/kg daily) and deferoxamine (DFO, 35-50mg/kg on 3-7 days/week) in 22
      patients with persistent iron overload or organ damage. In the 18 subjects
      completing 12 months of therapy, median liver iron concentration decreased by 31%
      from 17.4 mg/g (range 3.9-38.2mg/g) to 12.0mg/g (range 0.96-26.7 mg/g, p<0.001).
      Median ferritin decreased by 24% from 2465 ng/mL (range 1110-10,700 ng/mL) to
      1875 ng/mL (range 421-5800 ng/mL, p=0.002). All 6 subjects with elevated
      myocardial iron showed improvement in MRI T2* (p=0.031). The mean+/-S.E. plasma
      non-transferrin-bound iron (NTBI) declined from 3.10+/-0.25MUM to 2.15+/-0.29MUM
      (p=0.028). The administration of DFX during infusion of DFO further lowered NTBI
      (-0.28+/-0.08 MUM, p=0.004) and labile plasma iron (LPI, -0.03+/-0.01 MUM,
      p=0.006). The simultaneous administration of DFO and DFX rapidly reduced systemic
      and myocardial iron, and provided an excellent control of the toxic labile plasma
      iron species without an increase in toxicity.

PMID- 23151375
TI  - Testing evolutionary theories of discriminative grandparental investment.
AB  - This study tests two evolutionary hypotheses on grandparental investments
      differentiated by the child's sex: the paternity uncertainty hypothesis and the
      Trivers-Willard hypothesis. Data are from two culturally different countries: the
      Dutch Longitudinal Aging Study Amsterdam (n=2375) and the Chinese Anhui Survey
      (n=4026). In the Netherlands, grandparental investments are biased towards
      daughters' children, which is in accordance with the paternity uncertainty
      hypothesis. But in China, grandparental investments are biased towards sons'
      children, which is in conflict with the paternity uncertainty hypothesis. This
      study found no support for the Trivers-Willard hypothesis. These results raise
      doubts over the relevance of paternity uncertainty as an explanation of a
      grandparental investment bias towards daughters' children that is often found in
      Western populations. The results suggest that discriminative grandparental
      investments are better understood as the outcome of cultural prescriptions and
      economic motives.

PMID- 23151376
TI  - Uncovering the link between malfunctions in Drosophila neuroblast asymmetric cell
      division and tumorigenesis.
AB  - Asymmetric cell division is a developmental process utilized by several
      organisms. On the most basic level, an asymmetric division produces two daughter
      cells, each possessing a different identity or fate. Drosophila melanogaster
      progenitor cells, referred to as neuroblasts, undergo asymmetric division to
      produce a daughter neuroblast and another cell known as a ganglion mother cell
      (GMC). There are several features of asymmetric division in Drosophila that make
      it a very complex process, and these aspects will be discussed at length. The
      cell fate determinants that play a role in specifying daughter cell fate, as well
      as the mechanisms behind setting up cortical polarity within neuroblasts, have
      proved to be essential to ensuring that neurogenesis occurs properly. The role
      that mitotic spindle orientation plays in coordinating asymmetric division, as
      well as how cell cycle regulators influence asymmetric division machinery, will
      also be addressed. Most significantly, malfunctions during asymmetric cell
      division have shown to be causally linked with neoplastic growth and tumor
      formation. Therefore, it is imperative that the developmental repercussions as a
      result of asymmetric cell division gone awry be understood.

PMID- 23151377
TI  - Quantification of active and total transforming growth factor-beta levels in
      serum and solid organ tissues by bioassay.
AB  - BACKGROUND: Transforming growth factor-beta (TGF-beta) is a multi-factorial
      peptide growth factor that has a vital role in the regulation of cell growth,
      differentiation, inflammation, and tissue repair. Quantification of biologically
      active TGF-beta levels in tissues is crucial to illustrate mechanisms involved in
      various physiological and pathological processes, but direct measurement of
      bioactive TGF-beta level in the tissue has been hampered by lack of reliable
      methods. Here, we introduced mink lung epithelial cell bioassay to quantify both
      active and total TGF-beta levels in serum and protein lysates from solid organs
      in the mouse model. FINDINGS: Mink lung epithelial cells were stably transfected
      with plasminogen activator inhibitor-1 promoter/luciferase construct, in which
      bioactive TGF-beta level was represented by luciferase activity. Serum total TGF
      beta levels were comparable between the bioassay and enzyme-linked immunosorbent
      assay (ELISA), but active TGF-beta levels measured by ELISA were significantly
      lower than those obtained by the bioassay. Active and total TGF-beta levels in
      the solid organs including heart, liver, and kidney were also measured. Total TGF
      beta levels were relatively comparable among these organs, but active TGF-beta
      levels were slightly higher in hearts and kidneys than in livers. Positive
      luciferase activities in the bioassay were almost completely inhibited by adding
      pan-TGF-beta neutralizing antibodies, suggesting its high specificity to
      bioactive TGF-beta. We also measured myocardial TGF-beta levels after myocardial
      infarction and sham control by the bioassay, and compared the values with those
      obtained by ELISA. The bioassay demonstrated that both active and total tissue
      TGF-beta levels were significantly higher in post-myocardial infarction than in
      sham myocardium. ELISA was markedly less sensitive in detecting both active and
      total TGF-beta levels than our bioassay and failed to show any statistically
      significant difference in TGF-beta levels between myocardial infarction and sham
      myocardium. CONCLUSIONS: Our data suggested that the bioassay was significantly
      more sensitive than ELISA in detecting active TGF-beta in serum and both active
      and total TGF-beta in solid organ tissues. The bioassay will be useful in
      investigating TGF-beta profile in various solid organs in physiological and
      pathological conditions.

PMID- 23151378
TI  - Quality and mutagenicity of water and sediment of the streams impacted by the
      former uranium mine area Olsi-Drahonin (Czech Republic).
AB  - The water quality research performed in the years 2003-2010 demonstrated an
      impact of the mine water pumped from the closed Olsi uranium mine and discharged
      from the mine water treatment plant (MWTP) and groundwater from springs in the
      area on the water quality of the Haduvka stream. The water ecosystems of the
      lower part of the Haduvka stream are impacted mainly by water originated from the
      springs located in the stream valley and drained syenit subsoil, naturally rich
      in uranium. Those inflows caused a very high concentration of uranium measured in
      the water of the stream, which exceeds the given limit value. No negative impact
      on the water ecosystems of the receiving Bobruvka River was found. This reduction
      of impact is caused by five times higher average daily flow rate of the Bobruvka
      River in comparison with the Haduvka stream, which results in a sufficient
      dilution of pollution from the Haduvka.

PMID- 23151379
TI  - Mycobacterium bovis vertebral osteomyelitis and discitis with adjacent mycotic
      abdominal aortic aneurysm caused by intravesical BCG therapy: a case report in an
      elderly gentleman.
AB  - The bacille Calmette-Guerin, a live attenuated form of Mycobacterium bovis, has
      been used as anti-cancer immunotherapy for superficial bladder cancer since 1976
      [  1]. It is now the mainstay of therapy for this condition, which is partly
      attributable to the low complication rate; indeed 95% have no significant side
      effects [  2]. However, proven disseminated M. bovis infection has been
      documented, as is the case with our elderly patient.

PMID- 23151380
TI  - Multiple organ dysfunction: a delayed envenomation syndrome caused by tentacle
      extract from the jellyfish Cyanea capillata.
AB  - The delayed jellyfish envenomation syndrome (DJES) with serious multiple organ
      dysfunction or systemic damages, generally developed 2 h after jellyfish stings,
      deserves special attention for it is very meaningful to the clinical
      interventions. To set up a DJES model as well as to obtain more details about its
      process, an integrative approach, including clinical chemistry, pathology and
      immunohistochemistry, was conducted to simultaneously monitor the effects of
      tentacle extract (TE) from the jellyfish Cyanea capillata on the vital target
      organs (heart, lung, liver and kidney). Our results showed that the TE from C.
      capillata could induce diverse toxic effects on these organs, among which the
      liver and kidney injuries seemed to be more serious than cardiopulmonary injuries
      and might be the leading causes of death in rats with DJES. In summary, we have
      established a DJES model with multiple organ dysfunction, which could facilitate
      the research on its underlying mechanism as well as the development of specific
      prevention or therapy strategies against jellyfish envenomation. The application
      of this model suggested that the possible mechanism of DJES might be attributed
      to the synergy of cytotoxicity, vasoconstriction effect and other specific target
      organ toxicities of jellyfish venom.

PMID- 23151381
TI  - Effect of Australian elapid venoms on blood coagulation: Australian Snakebite
      Project (ASP-17).
AB  - Snake venoms contain toxins that activate the coagulation network and cause venom
      induced consumption coagulopathy. A previously developed mathematical model of
      the coagulation network was refined and used to describe and predict the time
      course of changes in the coagulation factors following envenomation by Brown
      snake (Pseudonaja spp.), Tiger snake (Notechis scutatus), Rough-scaled snake
      (Tropidechis carinatus) and Hoplocephalus spp. (Stephens banded, Pale headed and
      Broad headed). Simulations of the time course of the change in coagulation
      factors were compared to data obtained from a large prospective study of
      Australian snake bites - the Australian Snakebite Project. The model predictions
      were also compared against data for partial and complete VICC obtained from the
      same study. The model simulations were used to understand the differences in
      consumption and recovery of clotting factors in partial versus complete VICC as
      well as among bites from different snake types. The model suggested that the
      venoms were absorbed almost instantaneously and provided a reasonable prediction
      of the observed concentration of clotting factors over time in patients bitten by
      Australian elapid snakes. The model predictions suggested a higher consumption of
      factors (fibrinogen, II and IX in particular) in patients with complete VICC
      compared to those with partial VICC. The model also predicted that snakes with
      "Xa-like" venoms may produce a less severe VICC than snakes with "Xa:Va-like"
      venoms.

PMID- 23151382
TI  - Pre-B cell colony enhancing factor (PBEF/NAMPT/Visfatin) and vascular endothelial
      growth factor (VEGF) cooperate to increase the permeability of the human
      placental amnion.
AB  - Fluid efflux across the region of the amnion overlying the placenta is an
      essential component of the intramembranous absorption pathway that maintains
      amniotic fluid volume homeostasis. Dysregulation of this pathway may result in
      adverse pregnancy outcomes, however the factors controlling amnion permeability
      are unknown. Here, we report a novel mechanism that increases placental amnion
      permeability. Pre-B Cell Colony Enhancing Factor (PBEF) is a stress-responsive
      cytokine expressed by the human amnion, and is known to induce Vascular
      Endothelial Growth Factor (VEGF) production by other cell types. Interestingly,
      VEGF is up-regulated in the ovine amnion when intramembranous absorption is
      augmented. In this study, we show that PBEF induced VEGF secretion by primary
      human amniotic epithelial cells (AEC) derived from the placental amnion, as well
      as from the reflected amnion that lines the remainder of the gestational sac.
      Further, PBEF treatment led to the increased expression of VEGFR2 in placental
      AEC, but not reflected AEC. To test the hypothesis that PBEF and VEGF increase
      placental amnion permeability, we monitored the transfer of 2',7'
      dichlorofluorescein (DCF) from the fetal to the maternal side of human amnion
      explants. A treatment regimen including both PBEF and VEGF increased the rate of
      DCF transfer across the placental amnion, but not the reflected amnion. In
      summary, our results suggest that by augmenting VEGFR2 expression in the
      placental amnion, PBEF primes the tissue for a VEGF-mediated increase in
      permeability. This mechanism may have important implications in amniotic fluid
      volume control throughout gestation.

PMID- 23151384
TI  - Hydrothermal synthesis and tunable luminescence of persimmon-like sodium
      lanthanum tungstate:Tb3+, Eu3+ hierarchical microarchitectures.
AB  - Persimmon-like NaLa(WO(4))(2) microarchitectures were prepared via hydrothermal
      process with using trisodium citrate (Na(3)Cit) as chelated reagent and
      characterized by X-ray diffraction (XRD), field emission scanning electron
      microscope (FE-SEM), photoluminescence (PL), and fluorescent dynamics. The
      influences of Na(3)Cit concentration, organic additivities, and reaction time on
      the morphologies of NaLa(WO(4))(2) phosphor were studied. The results revealed
      that Na(3)Cit species had double functions of strong ligand and structure
      directing reagent that could efficiently control the formation of persimmon-like
      NaLa(WO(4))(2) microarchitectures. The possible mechanism for the growth of
      persimmon-like NaLa(WO(4))(2) microarchitectures was attributed to the Ostwald
      ripening mechanism. The energy transfer from Tb(3+) to Eu(3+) in the persimmon
      like NaLa(WO(4))(2) phosphors was observed. The energy transfer efficiencies and
      emission colors can be tuned by changing the concentration of Eu(3+). Finally, it
      was deduced that the electric dipole-dipole interaction (D-D) is the main
      mechanism for energy transfer between Tb(3+) and Eu(3+) in the persimmon-like
      NaLa(WO(4))(2) phosphor.

PMID- 23151383
TI  - Diversity and transmission competence in lymphatic filariasis vectors in West
      Africa, and the implications for accelerated elimination of Anopheles-transmitted
      filariasis.
AB  - Lymphatic Filariasis (LF) is targeted for elimination by the Global Programme for
      the Elimination of Lymphatic Filariasis (GPELF). The strategy adopted is based on
      the density dependent phenomenon of Facilitation, which hypothesizes that in an
      area where the vector species transmitting Wuchereria bancrofti are Anopheles
      mosquitoes, it is feasible to eliminate LF using Mass Drug Administration (MDA)
      because of the inability of Anopheles species to transmit low-density
      microfilaraemia. Even though earlier studies have shown Anopheles species can
      exhibit the process of Facilitation in West Africa, observations point towards
      the process of Limitation in certain areas, in which case vector control is
      recommended. Studies on Anopheles species in West Africa have also shown genetic
      differentiation, cryptic taxa and speciation, insecticide resistance and the
      existence of molecular and chromosomal forms, all of which could influence the
      vectorial capacity of the mosquitoes and ultimately the elimination goal. This
      paper outlines the uniqueness of LF vectors in West Africa and the challenges it
      poses to the 2020 elimination goal, based on the current MDA strategies.

PMID- 23151385
TI  - Protein-resistance performance enhanced by formation of highly-ordered
      perfluorinated alkyls on fluorinated polymer surfaces.
AB  - In this paper, the relationship between the surface structure of fluorinated
      polymers and their protein-resistant property was studied by preparing films of
      poly(n-alkyl methacrylate) end-capped with 2-perfluorooctylethyl methacrylate
      (FMA) (PFMA(y)-ec-PnAMA(x)-ec-PFMA(y)) with various ordered structures of
      perfluorinated alkyls. These fluorinated polymers were synthesized via a
      controlled/living atom-transfer radical polymerization (ATRP) method. Both the
      surface free energy and the CF(3)/CF(2) ratio obtained by X-ray photoelectron
      spectroscopy (XPS) were employed to scale the ordered structures of the
      perfluorinated alkyls. Protein adsorption studies using fibrinogen as a test
      molecule were undertaken on the various films by XPS. The results show that the
      adsorbed mass of fibrinogen decreased linearly with increasing CF(3)/CF(2) ratio
      on the fluorinated polymer surfaces. When the CF(3)/CF(2) ratio reaches 0.26,
      there was almost no fibrinogen adsorption. This work not only demonstrates the
      design of a fluorinated copolymer film on glass substrate with desirable protein
      resistant performance, but also provides a fundamental understanding of how the
      orientation of perfluoroalkyl side chains affects protein-resistant behavior on
      fluorinated surfaces.

PMID- 23151386
TI  - Improved neurologic prognosis for a patient with propionic acidemia who received
      early living donor liver transplantation.
AB  - Despite medical therapy, patients with propionic academia (PA) still display a
      tendency to develop epilepsy. Patients with neonatal-onset PA who have received
      early living donor liver transplantation (LDLT) are limited in number, and the
      effect on neurologic prognosis, including epilepsy, is not clear. We report a
      patient with PA whose EEG findings improved dramatically after undergoing LDLT at
      age 7 months. The patient's neurologic development and brain MRI findings were
      quite satisfactory at age 2 years and 3 months. LDLT is effective not only in
      preventing metabolic decompensation, but also in improving neurologic function to
      ensure better quality of life.

PMID- 23151388
TI  - Prevalence of consanguineous marriages in west and south of Afghanistan.
AB  - The prevalence of consanguinity in eight provinces of Afghanistan has recently
      been reported by Saify & Saadat (2012). The present cross-sectional study was
      done in order to illustrate the prevalence and types of consanguineous marriages
      among other populations of Afghanistan. Data on types of marriages were collected
      using a simple questionnaire. The total number of couples in this study was 5200
      from the following provinces: Farah, Ghazni, Herat, Hilmand, Kabul, Kandahar,
      Logar, Parwan and Wardak. Consanguineous marriages were classified by the degree
      of relationship between couples: double first cousins, first cousins, first
      cousins once removed, second cousins and beyond second cousins. The coefficient
      of inbreeding (F) was calculated for each couple and the mean coefficient of
      inbreeding (alpha) estimated for each population. The alpha in the country was
      0.0226, ranging from 0.0203 in Farah province to 0.0246 in Herat province. There
      were significant differences between provinces for frequencies of different types
      of marriages (p<0.001). First cousin marriages (21.7%) were the most common type
      of consanguineous marriages, followed by second cousins (16.0%), first cousins
      once removed (14.0%), beyond second cousins (6.9%) and double first cousins
      (1.6%). There was significant difference between ethnic groups for the types of
      marriages (p<0.001). Tajiks (Soni) and Sadats showed the lowest (alpha=0.0215)
      and highest (alpha=0.0242) levels of consanguinity among ethnic groups in
      Afghanistan, respectively. The present study shows that the Afghani populations,
      the same as other Islamic populations, have high levels of consanguinity.

PMID- 23151387
TI  - Sequencing from dried blood spots in infants with "false positive" newborn screen
      for MCAD deficiency.
AB  - BACKGROUND: Newborn screening (NBS) for medium chain acyl-CoA dehydrogenase
      deficiency (MCADD), one of the most common disorders identified, uses measurement
      of octanoylcarnitine (C8) from dried blood spots. In the state of Ohio, as in
      many places, primary care providers, with or without consultation from a
      metabolic specialist, may perform "confirmatory testing", with the final
      diagnostic decision returned to the state. Confirmatory testing may involve
      measurement of metabolites, enzyme analysis, mutation screening, or sequencing.
      We now report sequencing results for infants said to have "false positive" NBS
      results for MCAD deficiency, or who died before confirmatory testing could be
      performed. METHODS: Dried blood spots (DBS) were obtained from all 18 available
      NBS cards identified as "false positive" by NBS for the 3 year period after
      screening began in Ohio in 2003 (N=20, thus 2 had no DBS available), and from all
      6 infants with abnormal screens who died before confirmatory testing could be
      obtained. DNA extracted from DBS was screened for the common c.985A>G mutation in
      exon 11 of the ACADM gene, using a specific restriction digest method, followed
      by sequencing of the 12 exons, intron-exon junctions, and several hundred base
      pairs of the 5' untranslated region. RESULTS: The NBS cut-off value for C8 used
      was 0.7 MUmol/L. Sequencing of ACADM in six neonates with elevated C8 on NBS who
      died before confirmatory testing was obtained did not identify any significant
      variants in the coding region of the gene, suggesting that MCADD was not a
      contributing factor in these deaths. The mean C8 for the 18 surviving infants
      labeled as "False Positives" was 0.90 (95%CI 0.77-1.15), much lower than the mean
      value for confirmed cases. Ten of the 18 were premature births weighing <1200 g,
      the rest were normal sized and full term. Eight infants, mostly full term with
      appropriate birth weight, were heterozygous for the common c.985A>G mutation; one
      of those also has a novel sequence change identified in exon 9 that predicts a
      PRO to LEU change at residue 258 of the protein. Both the phase and any possible
      clinical significance of the variant are unknown, but several lines of evidence
      suggest that it could lead to protein malfunction. That child had an NBS C8 of
      2.2, more than double the mean for the False Positive group. Unfortunately, the
      study design did not provide clinical outcome data, but the child is not known to
      have presented clinically by age 7 years. CONCLUSIONS: These results suggest that
      sequencing of ACADM from dried blood spots can be one useful follow-up tool to
      provide accurate genetic counseling in the situation of an infant with elevated
      C8 on NBS who dies before confirmatory testing is obtained. Of surviving
      neonates, there appear to be two populations of infants with false positive NBS
      C8 values: 1) term AGA infants who are heterozygous for the common c.985A>G
      mutation, and, 2) premature infants, regardless of carrier status. The finding of
      two sequence variants in an infant reported to the state as not affected suggests
      the possibility that some infants with two mutations may be reported as normal at
      follow-up. State registries may wish to consider asking that metabolic
      specialists, who are most familiar with the variability of these rare disorders,
      be involved in the final diagnostic evaluation. Finally, providers may wish to
      consider ACADM sequencing, or other diagnostic testing, as part of the
      confirmatory evaluation for infants with NBS C8 concentrations that are
      significantly above the cut-off value, even if plasma and urine metabolites are
      not strikingly increased.

PMID- 23151389
TI  - Canavan disease, a rare early-onset human spongiform leukodystrophy: insights
      into its genesis and possible clinical interventions.
AB  - The brain contains high concentrations of the amino acid N-acetyl-l-aspartate
      (NAA) and its' glutamate adduct N-acetyl-l-aspartylglutamate (NAAG), both
      synthesized primarily by and stored in neurons. Upon depolarization both are
      exported to extracellular fluid (ECF) with NAA targeted to oligodendrocytes and
      NAAG targeted to astrocytes where they are hydrolyzed by specific enzymes. While
      the functions of these substances are incompletely known, their unique tri
      cellular metabolism is apparently vital to normal brain function. Canavan disease
      (CD) is a globally occurring but rare early-onset human spongiform leukodystrophy
      associated with inborn genetic errors affecting the activity of aspartoacylase
      (ASPA), the enzyme highly expressed in oligodendrocytes that hydrolyzes NAA.
      Several hypotheses attempt to explain how the lack of ASPA activity results in
      the inability of oligodendrocytes to build or maintain axon-enveloping myelin
      sheaths, a failure reflected in the CD syndrome by profound neurological
      disturbances. Based on evidence provided by recent studies, as well as on
      descriptions of several atypical mild cases of CD and of a singular human case of
      an inborn error where NAA cannot be synthesized, we provide insights into the
      possible genesis of the CD syndrome and many of its phenotypic expressions. In
      this article we also evaluate current hypotheses, and discuss possible clinical
      interventions that may be of value in treatment of CD.

PMID- 23151390
TI  - Neural responses to threat and reward interact to predict stress-related problem
      drinking: A novel protective role of the amygdala.
AB  - BACKGROUND: Research into neural mechanisms of drug abuse risk has focused on
      the role of dysfunction in neural circuits for reward. In contrast, few studies
      have examined the role of dysfunction in neural circuits of threat in mediating
      drug abuse risk. Although typically regarded as a risk factor for mood and
      anxiety disorders, threat-related amygdala reactivity may serve as a protective
      factor against substance use disorders, particularly in individuals with
      exaggerated responsiveness to reward. FINDINGS: We used well-established
      neuroimaging paradigms to probe threat-related amygdala and reward-related
      ventral striatum reactivity in a sample of 200 young adult students from the
      ongoing Duke Neurogenetics Study. Recent life stress and problem drinking were
      assessed using self-report. We found a significant three-way interaction between
      threat-related amygdala reactivity, reward-related ventral striatum reactivity,
      and recent stress, wherein individuals with higher reward-related ventral
      striatum reactivity exhibit higher levels of problem drinking in the context of
      stress, but only if they also have lower threat-related amygdala reactivity. This
      three-way interaction predicted both contemporaneous problem drinking and problem
      drinking reported three-months later in a subset of participants. CONCLUSIONS:
      These findings suggest complex interactions between stress and neural
      responsiveness to both threat and reward mediate problem drinking. Furthermore,
      they highlight a novel protective role for threat-related amygdala reactivity
      against drug use in individuals with high neural reactivity to reward.

PMID- 23151391
TI  - Being in-between and lost in the discharge process--an excursus of two empirical
      studies of older persons', their relatives', and care professionals' experience.
AB  - The discharge process (DP) is full of well-known risks, and a comprehensive and
      well-executed DP is especially important for older people with multiple health
      problems and continuing care needs, as well as for their relatives. Few studies
      focus on the experiences with the DP by older people in need of home care nursing
      and their relatives. Therefore, the aim was to deepen the understanding of the DP
      as a phenomenon described by older people, their relatives, and care
      professionals. The method is an excursus of the findings of two previously
      published research studies. By using the Reflective Lifeworld Research approach,
      the empirical findings were further interpreted with lifeworld theory. The
      results describe the essential meaning of the phenomenon of DP in relation to
      healthcare needs. The illness and the DP can be viewed as a course of action
      where the familiar becomes unfamiliar for older people and their relatives,
      entailing an insecure future existence characterized by the experience of being
      in-between. The DP is marked by bodily and existential needs. The older persons
      and their relatives are lost in the hospital context and trying to influence life
      and adapt to life circumstances, while being relentlessly dependent on care
      professionals. Care professionals work from both an organizational and a medical
      approach. Disharmony and disagreement seem to arise easily among the
      professionals regarding the planning negatively affecting the patients and their
      relatives. More efforts are needed in the DP to empower older people and their
      relatives to go on with their life at home. The caring practice needs to more
      clearly meet and address the individual needs of older people and their relatives
      and their understanding of their illness. It needs to give them lifeworld and
      life goals to alleviate their suffering and to help them adjust to their new
      situation.

PMID- 23151392
TI  - Support systems for and barriers to diabetes management in South Asians and
      Whites in the UK: qualitative study of patients' perspectives.
AB  - OBJECTIVES: To explore experiences of UK-based South Asian and White patients
      with diabetes in relation to their support systems for and barriers to diabetes
      management. DESIGN: Qualitative study (semistructured interviews analysed using a
      form of Interpretative Phenomenological Analysis). PARTICIPANTS: 20 outpatients
      with diabetes (12 British South Asians and 8 British Whites) with either good or
      poor glycaemic control. SETTING: Hillingdon Hospital, Uxbridge, UK. RESULTS:
      Qualitative analysis revealed distinct themes for the two ethnic groups. For the
      South Asian participants, challenges surrounding diet management and social
      stigma attached to having diabetes were the two predominant barriers to effective
      diabetes management. Support from immediate family members was commonly reported
      as a strong support system for optimising diabetes management by the South Asian
      sample in addition to the perceived positive impact of religion (healing power of
      prayer), the valuable informational support from their diabetes-care team,
      patient leaflets and diabetes magazines. Similar to the South Asians, adhering to
      dietary recommendations was the most difficult aspect of diabetes management for
      the White participants followed by the inconveniences surrounding injecting
      insulin. The hospital diabetes-care team was considered as the most effective
      support system for diabetes management by the White sample and interestingly,
      this was the only dominant theme in their reported sources of support.
      CONCLUSIONS: Both South Asian and White participants emphasised adherence to
      dietary recommendations as the most difficult aspect of living with diabetes. In
      addition, social stigma attached to diabetes was a prominent concern among South
      Asian participants that seemed to have a significant negative impact on their
      diabetes control and overall management. Given South Asian patients' reliance on
      their family for the management of their condition, interventions targeting
      improved diabetes outcomes in this population may prove more successful if they
      are designed to involve significant family members.

PMID- 23151394
TI  - How might the London 2012 Olympics influence health and the determinants of
      health? Local newspaper analysis of pre-Games pathways and impacts.
AB  - OBJECTIVES: To conduct a content analysis of pre-Games local media coverage of
      the potential impact on health and the determinants of health in Newham, the site
      of the Olympic Park. DESIGN: Local newspaper content analysis. SETTING: Olympic
      park host site of the London Borough of Newham. OUTCOME MEASURES: Media coverage
      of employment, physical activity and well-being. RESULTS: Three hundred and 51
      articles meeting the inclusion criteria were included in the analysis. The
      overwhelming majority of the articles took a positive perspective on the Olympic
      Games being hosted in Newham with less than 10% (32/351) addressing potential
      adverse effects. The frequency of articles reporting on both employment and well
      being increased significantly over time (p=0.002 and p=0.006, respectively). A
      non-significant increasing trend was observed for physical activity (p=0.146).
      New employment opportunities and the promotion of physical activity in young
      people were the pathways most frequently reported in the local media. However,
      much less attention is devoted to understanding the uncertainties about how much
      of these new opportunities will directly improve the determinants of health in
      the Newham population. CONCLUSIONS: Pre-Games reporting on the impact on health
      and the determinants of health increased over time in the London Borough of
      Newham, and is overwhelmingly positive. However, specific uncertainties around
      the true nature of its impact on local employment and physical activity were
      articulated. Further evaluation of the tangible impacts on population health, and
      the determinants of health and health inequalities from the London 2012 Olympics,
      is required.

PMID- 23151393
TI  - Assessment of simple risk markers for early mortality among HIV-infected patients
      in Guinea-Bissau: a cohort study.
AB  - BACKGROUND: Decisions about when to start an antiretroviral therapy (ART) are
      normally based on CD4 cell counts and viral load (VL). However, these
      measurements require equipment beyond the capacity of most laboratories in low
      income and middle-income settings. Thus, there is an urgent need to identify and
      test simple markers to guide the optimal time for starting and for monitoring the
      effect of ART in developing countries. OBJECTIVES: (1) To evaluate anthropometric
      measurements and measurement of plasma-soluble form of the urokinase plasminogen
      activator receptor (suPAR) levels as potential risk factors for early mortality
      among HIV-infected patients; (2) to assess whether these markers could help
      identify patients to whom ART should be prioritised and (3) to determine if these
      markers may add information to CD4 cell count when VL is not available. DESIGN:
      An observational study. SETTING: The largest ART centre in Bissau, Guinea-Bissau.
      PARTICIPANTS: 1083 ART-naive HIV-infected patients. OUTCOME MEASURES:
      Associations between baseline anthropometric measurements, CD4 cell counts,
      plasma suPAR levels and survival were examined using Cox proportional hazards
      models. RESULTS: Low body mass index (BMI<=18.5 kg/m(2)), low mid-upper-arm
      circumference (MUAC<=250 mm), low CD4 cell count (<=350 cells/MUl) and high suPAR
      plasma levels (>5.3 ng/ml) were independent predictors of death. Furthermore,
      mortality among patients with low CD4 cell count, low MUAC or low BMI was
      concentrated in the highest suPAR quartile. CONCLUSIONS: Irrespective of ART
      initiation and baseline CD4 count, MUAC and suPAR plasma levels were independent
      predictors of early mortality in this urban cohort. These markers could be useful
      in identifying patients at the highest risk of short-term mortality and may aid
      triage for ART when CD4 cell count is not available or when there is shortness of
      antiretroviral drugs.

PMID- 23151395
TI  - Efficacy of multimodal, systematic non-surgical treatment of knee osteoarthritis
      for patients not eligible for a total knee replacement: a study protocol of a
      randomised controlled trial.
AB  - INTRODUCTION: It is recommended that non-operative treatment of knee
      osteoarthritis (KOA) should be individually tailored and include multiple
      treatment modalities. Despite these recommendations, no one has yet investigated
      the efficacy of combining several non-surgical treatment modalities in a
      randomised controlled study. The purpose of this randomised controlled study is
      to examine if an optimised, combined non-surgical treatment programme results in
      greater improvements in pain, function and quality of life in comparison with
      usual care in patients with KOA who are not eligible for total knee arthroplasty
      (TKA). METHODS AND ANALYSIS: This study will include 100 consecutive patients
      from the North Denmark Region not eligible for TKA with radiographic KOA (K-L
      grade >=1) and mean pain during the previous week of <=60 mm (0-100). The
      participants will be randomised to receive either a 12-week non-surgical
      treatment programme consisting of patient education, exercise, diet, insoles,
      paracetamol and/or NSAIDs or usual care (two information leaflets containing
      information on KOA and advice regarding the above non-surgical treatment). The
      primary outcome will be the change from baseline to 12 months on the self-report
      questionnaire Knee Injury and Osteoarthritis Outcome Score (KOOS)(4) defined as
      the average score for the subscale scores for pain, symptoms, activities of daily
      living and quality of life. Secondary outcomes include the five individual KOOS
      subscale scores, pain on a 100 mm Visual Analogue Scale, EQ-5D, self-efficacy,
      pain pressure thresholds, postural control and isometric knee flexion and knee
      extension strength. ETHICS AND DISSEMINATION: This study was approved by the
      local Ethics Committee of The North Denmark Region (N-20110085) and the protocol
      conforms to the principles of the Declaration of Helsinki. Data collection will
      be completed by April 2014. Publications will be ready for submission in the
      summer of 2014. TRIAL REGISTRATION NUMBER: This study is registered with
      http://clinicaltrials.gov (NCT01535001).

PMID- 23151396
TI  - Optimizing molluscicide treatment strategies in different control stages of
      schistosomiasis in the People's Republic of China.
AB  - BACKGROUND: The application of chemical molluscicides is still one of the most
      effective measures for schistosomiasis control in P. R. China. By applying
      diverse molluscicide treatment scenarios on different snail densities in the
      field, we attempted to understand the cost-effectiveness of molluscicide
      application so as to prescribe an optimal management approach to control
      intermediate host snail Oncomelania hupensis under acceptable thresholds based on
      the goal of the National Schistosomiasis Control Programme. METHODS: The
      molluscicidal field trial was carried out in the marshland of an island along the
      Yangtze River, Jiangsu province, P.R. China in October 2010. Three plots in the
      island representing low-density, medium-density and high-density groups were
      identified after the baseline survey on snail density. Each snail density plot
      was divided into four experimental units in which molluscicide (50% niclosamide
      ethanolamine salt wettable powder) was applied once, twice, trice and four times,
      respectively. The logistic regression model to correlate snail mortality rate
      with the covariates of number of molluscicidal treatment and snail density, and a
      linear regression model to investigate the relationship between cost
      effectiveness and number of molluscicidal treatment as well as snail density were
      established. RESULTS: The study revealed that increase in the number of
      molluscicide treatments led to increased snail mortality across all three
      population density groups. The most cost-effective regimen was seen in the high
      snail density group with a single molluscicide treatment. For both high and low
      density groups, the more times molluscicide were applied, the less cost
      effectiveness was. However, for the median density group, the level of cost
      effectiveness for two applications was slightly higher than that in one time.
      CONCLUSIONS: We concluded that different stages of the national schistosomiasis
      control/elimination programme, namely morbidity control, transmission control and
      transmission interruption, should utilize different molluscicide treatment
      strategies to maximize cost-effectiveness.

PMID- 23151397
TI  - Take it as read: origins of trust in knowledge gained from print.
AB  - The ability to read opens up the possibility of learning about the world
      indirectly via print sources, providing a powerful new opportunity for children
      who have for years learned effectively from what people tell them. We compared
      children's trust in printed versus oral information. We also examined whether
      children who showed preferential trust in an informant with print assumed that
      the informant was still reliable about new information offered without print
      support. Children (N=89 aged 3-6 years) received conflicting suggestions from two
      dolls about which picture showed an unfamiliar target. Only one doll's suggestion
      referred to a printed label read aloud. Prereaders, despite their exposure to
      print and presumed experience of others treating print sources as authoritative,
      showed no clear evidence of preferential trust in the suggestions with print
      support. Early readers, in contrast, consistently preferred the suggestions with
      print support. Importantly, despite having treated the doll with print as having
      a history of accuracy, early readers no longer showed trust in that doll when it
      subsequently had no print support. Children at the very earliest stages of
      reading treated the doll with print appropriately as having gained only specific
      information from the print sources.

PMID- 23151398
TI  - The concurrent and predictive validity of symptomatic remission criteria in first
      episode schizophrenia.
AB  - BACKGROUND: Since the introduction of consensus criteria for symptomatic
      remission in 2005, most first-episode studies focused on cross-sectional
      relationship between remission status and functional outcome. Predictive validity
      of the proposed remission definition was under-studied. Relationship of remission
      with subjective quality of life (QoL) was inadequately addressed with
      inconsistent findings being observed. METHOD: One hundred and four Hong Kong
      Chinese aged 18 to 55years presenting with first-episode schizophrenia-spectrum
      disorder were studied. Socio-demographics, baseline clinical and functioning
      profiles were obtained. Psychopathological and functional reassessments were
      conducted at 6, 12 and 24months. Subjective QoL was measured at 12 and 24months.
      Symptomatic remission was operationally defined according to the consensus
      criteria developed by the Remission in Schizophrenia Working Group (RSWG),
      comprising both symptom-severity and 6-month duration components. RESULTS: At
      12months, 59.6% of patients achieved symptomatic remission. Remitted patients had
      significantly lower symptom severity, more favorable psychosocial functioning and
      better subjective QoL at 12months than non-remitted counterparts. Attainment of
      remission at 12months was significantly associated with fewer positive, negative,
      depressive and disorganization symptoms, higher levels of functioning and
      subjective QoL at 24months. Linear regression analysis indicated that remission
      status independently predicted functional outcome even when the effects of
      educational level, baseline functioning and negative symptom scores were
      controlled for. CONCLUSION: The operationally defined symptomatic remission
      formulated by the RSWG represented a clinically valid construct that was found to
      be closely related to both concurrent and longitudinal outcomes on
      psychopathology, functioning and subjective QoL in the early stage of
      schizophrenia.

PMID- 23151399
TI  - Access to contraceptive methods and prevalence of use.
AB  - Survey data on contraceptive use for about 80 countries are related to measures
      of contraceptive access, by method, from 1999 to 2009. Cross-tabulation and
      correlational methods are employed, with geographic comparisons and time trends.
      Total prevalence of use for five modern contraceptive methods correlates well to
      a variety of access measures. Greater access is also accompanied by a better
      balance among methods for both access and use. Sub-Saharan African countries show
      similar patterns though at lower levels. Improved access to multiple methods is
      consistently associated with higher levels of contraceptive use.

PMID- 23151400
TI  - In situ formation deposited ZnO nanoparticles on silk fabrics under ultrasound
      irradiation.
AB  - Deposition of zinc(II) oxide (ZnO) nanoparticles on the surface of silk fabrics
      was prepared by sequential dipping steps in alternating bath of potassium
      hydroxide and zinc nitrate under ultrasound irradiation. This coating involves in
      situ generation and deposition of ZnO in a one step. The effects of ultrasound
      irradiation, concentration and sequential dipping steps on growth of the ZnO
      nanoparticles have been studied. Results show a decrease in the particles size as
      increasing power of ultrasound irradiation. Also, increasing of the concentration
      and sequential dipping steps increase particle size. The physicochemical
      properties of the nanoparticles were determined by powder X-ray diffraction
      (XRD), scanning electron microscopy (SEM) and wavelength dispersive X-ray (WDX).

PMID- 23151402
TI  - The enigmatic root cell - emerging roles contributing to fluid homeostasis within
      the cochlear outer sulcus.
AB  - Despite their curious morphology prompting numerous hypotheses of their normal
      function, the root cells lining the cochlear outer sulcus have long evaded
      physiological characterization. A growing body of evidence now suggests that they
      regulate the solute content of the endolymph and/or the perilymph, and may be
      essential in safe-guarding the global homeostasis of the cochlea. Immuno-labeling
      experiments have demonstrated polarized expression of key ion transport proteins,
      and recent electrophysiological recordings have identified specific membrane
      conductances. These studies have painted a clearer picture of how this unusual
      cell type may contribute to the maintenance of sound transduction, and how they
      may be central to pathological processes associated with various forms of hearing
      loss. This article is part of a Special Issue entitled "Annual Reviews 2013". 

PMID- 23151403
TI  - Do randomized clinical trials with inadequate blinding report enhanced placebo
      effects for intervention groups and nocebo effects for placebo groups? A protocol
      for a meta-epidemiological study of PDE-5 inhibitors.
AB  - BACKGROUND: Patients' expectations of treatment effects may contribute to
      positive (placebo) and negative (nocebo) outcomes. The effect of patient
      expectations may be pronounced in subjectively assessed conditions, such as male
      erectile dysfunction. The aim of this project is to examine the magnitude of
      expectancy in trials of phosphodiesterase-5 inhibitors. We hypothesize that
      randomized controlled trials with inadequate blinding will report enhanced
      placebo effects for intervention groups and nocebo effects for placebo groups,
      compared with adequately blinded studies. METHODS/DESIGN: We will quantify the
      magnitude of expectancy by comparing the effect estimates of trials with
      inadequate and adequate blinding. Blinding will be assessed using four domains
      from the Cochrane 'risk-of-bias' tool: allocation concealment; blinding of
      patient; caregiver; and outcome assessor. Our secondary aim is to identify
      factors that can modify expectations, such as prior experience with the
      intervention and drug side effects.We will perform an electronic search using a
      combination of controlled vocabulary and free text words in the following
      databases: MEDLINE, EMBASE, CENTRAL, and a clinical trials register. We will
      include randomized controlled trials, with either parallel or crossover design,
      that compare one phosphodiesterase-5 inhibitor with a placebo. The study's
      primary aim should be to investigate the efficacy of phosphodiesterase-5
      inhibitors for treating male erectile dysfunction. Screening will take place at
      two levels: abstracts and titles, followed by full text reports. Two reviewers
      will independently extract data on the primary outcome and assess risk of bias.We
      will meta-analyze treatment effects, if appropriate, to assess the magnitude of
      enhanced placebo effects and nocebo effects in intervention and placebo groups,
      respectively. We will explore possible mediators of placebo and nocebo effects
      with subgroup and meta-regression analyses. DISCUSSION: Treatments may confer
      significant costs and risk of adverse effects; it is important, therefore, to
      determine whether the effects of treatments are larger than expectancy alone. If
      treatment expectations can be used in a non-deceptive way to produce clinically
      advantageous outcomes, then it may be possible to incorporate such mechanisms
      into evidence-based healthcare decision-making.

PMID- 23151404
TI  - Expert evidence by mental health professionals: the communication challenge posed
      by evidence about Autism Spectrum Disorder, brain injuries, and Huntington's
      Disease.
AB  - By drawing upon mental health assessment issues about three non-mainstream
      conditions - Autism Spectrum Disorder, brain injuries, including Foetal Alcohol
      Syndrome, and Huntington's Disease - the author argues for the need for subtle,
      empathic and informed expert evidence about the potential nexus between such
      conditions and accused persons' criminal responsibility and culpability. He
      contends that what is forensically required is enhancement of the capacity of
      triers of fact to appreciate informedly and authentically, sometimes in a nuanced
      way, how persons with different, damaged or deteriorating brains experience
      situations and others' behaviour so that accused persons' conduct can fairly be
      evaluated without imposition of assumptions or expectations in respect of "normal
      persons" that may not be apposite.

PMID- 23151406
TI  - Polymorphisms of the fat mass and obesity-associated gene and the increased risk
      of systemic carcinogenesis.

PMID- 23151407
TI  - The European Commission should require better medicines, not just faster
      reimbursements.

PMID- 23151405
TI  - Association of C-reactive protein and interleukin-6 with new-onset fatigue in the
      Whitehall II prospective cohort study.
AB  - BACKGROUND: Although basic research on neuroimmune interactions suggests that
      inflammatory processes may play a role in the development of fatigue, population
      based evidence on this association is limited. This study examined whether plasma
      C-reactive protein (CRP) and interleukin-6 (IL-6), biomarkers of systemic
      inflammation, predict fatigue onset. METHOD: The Whitehall II study is a large
      scale cohort study conducted in 20 civil service departments in London. Plasma
      CRP and IL-6 were measured in 4847 non-fatigued participants at phase 3 (1991
      1993, aged 39-63 years). Fatigue was assessed using the Vitality subscale of the
      36-item Short Form Health Survey (SF-36) at phase 3 and phase 4 (1995-1996).
      RESULTS: During a mean follow-up of 3.1 years, 957 new fatigue cases (19.7%) were
      identified using the pre-established cut-off score of <= 50 on the Vitality
      subscale. CRP values were dichotomized as low (<1.0 mg/l ) or high (>= 1.0 mg/l)
      using the Centers for Disease Control/American Heart Association recommendations.
      Similarly, IL-6 values were also dichotomized as low (<1.5 pg/ml) or high (>= 1.5
      pg/ml). After full adjustment for sociodemographic and biobehavioral covariates,
      the odds ratios for new-onset fatigue were 1.28 [95% confidence interval (CI)
      1.09-1.49, p = 0.003] for high CRP and 1.24 (95% CI 1.06-1.45, p = 0.008) for
      high IL-6. Similar results were found when CRP and IL-6 were treated as
      continuous variables. CONCLUSIONS: Plasma CRP and IL-6 were prospectively
      associated with new-onset fatigue, supporting the hypothesis that low-grade
      inflammation has a role in the development of fatigue.

PMID- 23151409
TI  - Transparent layer constancy.
AB  - In transparency perception the visual system assigns transmission-related
      attributes to transparent layers. Based on a filter model of perceptual
      transparency we investigate to what extent these attributes remain constant
      across changes of background and illumination. On a computational level, we used
      computer simulations to test how constant the parameters of the filter model
      remain under realistic changes in background reflectances and illumination and
      found almost complete constancy. This contrasts with systematic deviations from
      constancy found in cross-context matches of transparent filters. We show that
      these deviations are of a very regular nature and can be understood as a
      compromise between a proximal match of the mean stimulus color and complete
      constancy as predicted by the filter model.

PMID- 23151408
TI  - Resistance to visceral leishmaniasis is severely compromised in mice deficient of
      bradykinin B2-receptors.
AB  - BACKGROUND: Kinins liberated from plasma-borne kininogens, are potent innate
      stimulatory signals. We evaluated whether resistance to infection by Leishmania
      (L.) chagasi depends on activation of G-protein coupled bradykinin B2 receptors
      (B2R). FINDINGS: B2R-/- C57BL/6 knock-out (KOB2) and B2R+/+ C57BL/6-wild type
      control mice (C57) were infected with amastigotes of Leishmania (L.) chagasi.
      Thirty days after infection, the KOB2 mice showed 14% and 32% relative increases
      of liver (p< 0.017) and spleen weights (p<0.050), respectively, whereas liver
      parasite load increased 65% (p< 0.011) in relation to wild type mice. The
      relative weight increases of liver and spleen and the parasite load were
      positively correlated (R = 0.6911; p< 0.007 to R = 0.7629; p< 0.001,
      respectively). Conversely, we found a negative correlation between the increased
      liver relative weight and the weakened DTH response (a strong correlate to
      protection or natural resistance to VL) or the decreased levels of IgG2b
      antibodies to leishmanial antigen. Finally, we also found that IFN-gamma
      secretion by splenocytes, an adaptive response that was significantly decreased
      in KOB2 mice (p< 0.002), was (i) negatively correlated to the increase in liver
      LDU (R = -0.6684; p = 0.035) and liver/body relative weight (R = -0.6946; p =
      0.026) and (ii) positively correlated to serum IgG2b levels (R = 0.8817; p =
      0.001). CONCLUSIONS: We found that mice lacking B2R display increased
      susceptibility to the infection by Leishmania (L.) chagasi. Our findings suggest
      that activation of the bradykinin/B2R pathway contributes to development of host
      resistance to visceral leishmaniasis.

PMID- 23151410
TI  - Visual stability across combined eye and body motion.
AB  - In order to maintain visual stability during self-motion, the brain needs to
      update any egocentric spatial representations of the environment. Here, we use a
      novel psychophysical approach to investigate how and to what extent the brain
      integrates visual, extraocular, and vestibular signals pertaining to this spatial
      update. Participants were oscillated sideways at a frequency of 0.63 Hz while
      keeping gaze fixed on a stationary light. When the motion direction changed, a
      reference target was shown either in front of or behind the fixation point. At
      the next reversal, half a cycle later, we tested updating of this reference
      location by asking participants to judge whether a briefly flashed probe was
      shown to the left or right of the memorized target. We show that updating is not
      only biased, but that the direction and magnitude of this bias depend on both
      gaze and object location, implying that a gaze-centered reference frame is
      involved. Using geometric modeling, we further show that the gaze-dependent
      errors can be caused by an underestimation of translation amplitude, by a bias of
      visually perceived objects towards the fovea (i.e., a foveal bias), or by a
      combination of both.

PMID- 23151411
TI  - There's more behind it: perceived depth order biases perceived
      numerosity/density.
AB  - Humans have a clear sense of the numerosity of elements in a surface. However,
      recent studies showed that the binding of features to the single elements is
      severely limited. By studying the relationship of depth order and perceived
      numerosity of overlapping, pseudotransparent surfaces, we show that the binding
      of elements to the surfaces is also limited. In transparent motion, anisotropies
      for perceived depth order and perceived numerosity were highly correlated:
      directions that were more likely to be perceived in the back were also more
      likely to be perceived as more numerous. The magnitude of anisotropies, however,
      was larger for depth order than for numerosity, and the correlation with eye
      movement anisotropies also developed earlier for depth order than for numerosity
      judgments. Presenting the surfaces at different disparities removed the
      anisotropies but lead to a consistent bias to overestimate the numerosity of the
      surface in the back and to underestimate the surface in the front. The magnitude
      of this bias did not depend on dot density or lifetime. However when the speed of
      motion was reduced or when the two surfaces were presented at different luminance
      polarities, the magnitude of anisotropies and the numerosity bias were greatly
      reduced. These results show that the numerosity of pseudotransparent surfaces is
      not processed independent of the depth structure in the scene. Instead there is a
      strong prior for higher numerosity in the back surface.

PMID- 23151412
TI  - Hemodynamic adaptation to pregnancy in women with structural heart disease.
AB  - BACKGROUND: Many women with structural heart disease reach reproductive age and
      contemplate motherhood. Pregnancy induces and requires major hemodynamic changes.
      Pregnant women with structural heart disease may have a reduced cardiac reserve.
      There are no longitudinal data on cardiovascular adaptation throughout pregnancy
      in women with structural heart disease. METHODS: Thirty-five women with
      structural heart disease were included in a prospective observational trial.
      Maternal hemodynamics were assessed before conception, during pregnancy and 6
      months postpartum by transthoracic echocardiography. Uteroplacental perfusion was
      analyzed by obstetric Dopplers. Longitudinal evolution over time was analyzed as
      well as the long term influence of pregnancy on cardiac function. RESULTS:
      Cardiac output (CO), stroke volume (SV), left ventricular mass (LV mass) and E/E'
      ratio significantly increased and ejection fraction (EF) and fractional
      shortening (FS) decreased during pregnancy. There was a statistically significant
      difference in EF, FS and E/E' ratio before and after pregnancy. CONCLUSIONS: The
      characteristic pattern of hemodynamic adaptation to pregnancy is attenuated in
      women with structural heart disease. The pregnancy related volume load induces
      progression of diastolic dysfunction. Our data suggest a persistent reduction in
      systolic and diastolic cardiac functions after pregnancy in women with structural
      heart disease.

PMID- 23151414
TI  - Serotype distribution and characteristics of antimicrobial resistance in Shigella
      isolated from Henan province, China, 2001-2008.
AB  - The serotype distribution and susceptibility to 14 antimicrobial agents of 526
      isolates of Shigella spp. from four hospitals in Sun county, Henan province,
      China during 2001-2008, were analysed to identify associations of serotypes with
      resistance trends. S. flexneri was the most frequent species (92.4%), the
      remainder was S. sonnei. The prevalent serotype of S. flexneri was 2a (26.7%).
      Almost all (>99%) isolates were resistant to tetracycline, nalidixic acid and
      pipemidic acid; >80% were resistant to chloramphenicol, amoxicillin and co
      trimoxazole but less than 5% were resistant to polymyxin B, furazolidone,
      cefotaxime and gentamicin. S. flexneri showed statistically significant higher
      resistance than S. sonnei to amoxicillin, ampicillin, chloramphenicol and
      ciprofloxacin but resistance to co-trimoxazole was more common in S. sonnei than
      in S. flexneri. These results emphasize that monitoring of emerging resistance in
      Shigella isolates is essential for timely and appropriate recommendations for
      antimicrobial therapy.

PMID- 23151413
TI  - MRI perfusion in determining pseudoprogression in patients with glioblastoma.
AB  - We examine the role of dynamic susceptibility contrast (DSC) magnetic resonance
      imaging (MRI) perfusion in differentiating pseudoprogression from progression in
      20 consecutive patients with treated glioblastoma. MRI perfusion was performed,
      and relative cerebral blood volume (rCBV), relative peak height (rPH), and
      percent signal recovery (PSR) were measured. Pseudoprogression demonstrated lower
      median rCBV (P=.009) and rPH (P<.001), and higher PSR (P=.039) than progression.
      DSC MRI perfusion successfully identified pseudoprogression in patients who did
      not require a change in treatment despite radiographic worsening following
      chemoradiotherapy.

PMID- 23151415
TI  - Efficacy and side effects of intravenous remifentanil patient-controlled
      analgesia used in a stepwise approach for labour: an observational study.
AB  - BACKGROUND: Remifentanil has a suitable pharmacological profile for labour
      analgesia. In this prospective, observational study, intravenous patient
      controlled analgesia with remifentanil, using stepwise bolus doses without
      background infusion, was examined during the first and second stages of labour.
      Outcomes were pain reduction, maternal satisfaction, maternal and neonatal side
      effects and remifentanil metabolism in the neonate. METHODS: Parturients with
      normal term singleton pregnancies were recruited. The initial remifentanil bolus
      dose was 0.15 MUg/kg, increasing in steps of 0.15 MUg/kg, with a 2-min lock-out.
      Pain scores using a 100 mm visual analogue scale, systolic and diastolic blood
      pressures, respiratory rate and maternal sedation were recorded every 15 min.
      Maternal oxygen saturation and heart rate were monitored continuously. Neonatal
      data included Apgar scores, clinical examination, naloxone use, resuscitation,
      umbilical cord blood gases and remifentanil concentrations. RESULTS: Forty-one
      parturients were enrolled. Pain scores were significantly reduced in the first 3
      h of patient-controlled analgesia use compared to baseline, and at the end of the
      first and second stages of labour (P<0.05). Maximal pain reduction was 60%
      (P<0.01). One patient had inadequate pain relief and converted to epidural
      analgesia. The mean highest dose of remifentanil was 0.7 MUg/kg [range 0.3-1.05].
      Ninety-three percent of patients were satisfied with their analgesia. The lowest
      oxygen saturation was 91% and the lowest respiratory rate was 9 breaths/min.
      Eleven parturients (27%) received supplemental oxygen due to oxygen saturations
      <92%. Maternal sedation was moderate, and neonatal data reassuring. CONCLUSIONS:
      Remifentanil intravenous patient-controlled analgesia provides adequate pain
      relief and high maternal satisfaction during the first and second stages of
      labour. Maternal sedation and respiratory depression may occur, but no serious
      neonatal side effects were recorded. Careful monitoring is mandatory.

PMID- 23151416
TI  - Genetic variants at 10q23 are associated with risk of head and neck cancer in a
      Chinese population.
AB  - BACKGROUND: A recent genome-wide association study (GWAS) focused on esophageal
      squamous cell carcinoma (ESCC) has identified several susceptible regions (5q11,
      21q22, 6p21 10q23, and 12q24) in Chinese population. We hypothesized that single
      nucleotide polymorphisms (SNPs) identified in these regions for ESCC were also
      associated with the risk of head and neck cancer (HNC) which share similar risk
      factors with ESCC. METHODS: To test this hypothesis, we genotyped three SNPs
      (rs2274223, rs2014300 and rs10484761) in a case-control study with 503 HNC cases
      and 900 cancer-free controls in a Chinese population. RESULTS: We found that
      rs2274223 was associated with a significantly increased risk of HNC in our
      population [GG vs. AA: adjusted odds ratio (OR)=1.86, 95% confidence interval
      (CI)=1.09-3.16; GG vs. (AG/AA): adjusted OR=1.85, 95% CI=1.09-3.12], and the
      effect appeared to be more prominent among drinkers (P=0.024) and patients with
      oral cavity cancer (P=0.019). In contrast, rs2014300 and rs10484761 variant were
      not observed any significantly association with risk of HNC. CONCLUSIONS: These
      results indicate that rs2274223 may be a marker SNP for HNC susceptibility in
      Chinese population.

PMID- 23151417
TI  - Reliability and validity of the Attitudes to Ageing Questionnaire (AAQ) in older
      people in Spain.
AB  - BACKGROUND: As ageing is a personal experience, an attitude to ageing
      questionnaire is essential for capturing the most realistic appraisal of this
      important stage of life. Our aim was to study the psychometric properties of the
      Attitudes to Ageing Questionnaire (AAQ) in a sample of Spanish older people.
      METHODS: A total of 242 participants aged 60 years and older were recruited from
      community centers, primary care centers, and family associations for the mentally
      ill and dementia. In addition to the AAQ, participants provided information on
      demographics, self-perception of health, comorbidity, health status (SF-12),
      depressive symptoms (GDS-30), and quality of life (WHOQOL-BREF and WHOQOL-OLD).
      Analysis was performed using standard psychometric techniques with SPSS v15.0.
      RESULTS: No floor and ceiling effects were found, and missing data were low. The
      internal consistency measured by Cronbach's alpha for AAQ subscales were 0.59,
      0.70, and 0.73. Exploratory Factor Analysis produced a three-factors solution
      accounting for 34% of the variance. A priori expected associations were found
      between some AAQ subscales with WHOQOL-BREF domains, with WHOQOL-OLD, SF-12, and
      the GDS-30 indicating good construct validity. In general, AAQ subscales
      differentiated between participants with lower and higher levels of education,
      and between a priori defined groups of older people (non-depressed vs. depressed;
      those with higher vs. lower physical comorbidities, and non-carers vs. carers).
      CONCLUSIONS: The Spanish version of the AAQ questionnaire showed acceptable
      psychometric properties in a convenience sample of Spanish older people. It is a
      useful measure of attitude for use with older people in social and clinical
      services.

PMID- 23151418
TI  - Measurement and validation of GHz-band whole-body average SAR in a human
      volunteer using reverberation chamber.
AB  - The World Health Organization's (WHO) recommendation on the need for further
      research for radio-frequency dosimetry has promoted studies on the whole-body
      average-specific absorption rate (WBA-SAR) in various kinds of anatomical-based
      numerical models. For experimental validation of GHz-band WBA-SARs in a real
      human, however, there have not so far been any published papers, despite the fact
      that, in 1982, Hill measured WBA-SARs at frequencies less than 40 MHz in human
      volunteers using a TEM-cell exposure system. In this study, we provide a
      measurement technique with a reverberation chamber for validating numerical
      dosimetry results on GHz-band WBA-SARs in living humans. We measured WBA-SARs at
      1, 1.5 and 2 GHz for a 22 year old male volunteer, with a height of 173 cm and a
      weight of 73 kg, in the reverberation chamber, and compared the results with the
      finite-difference time-domain (FDTD) simulation. The reverberation chamber was
      excited by using a signal generator through an amplifier with an output power of
      30-40 mW, which produced inside the chamber with the volunteer an average
      electric field strength of 5 V m(-1) equivalent to an average power spectral
      density of 6.6 MUW cm(-2). The WBA-SARs were obtained from the measured S(11) and
      S(21) together with the power density. On the other hand, the WBA-SARs have been
      calculated using the FDTD method for an adult male model with almost the same
      physique as that of the volunteer exposed to the electromagnetic field in the
      reverberation chamber. From the comparison between the measured and the
      calculated WBA-SARs, we could confirm that the measured GHz-band WBA-SARs
      approximately agree with the FDTD calculated results.

PMID- 23151419
TI  - Translating genomics to the clinic: implications of cancer heterogeneity.
AB  - BACKGROUND: Sequencing of cancer genomes has become a pivotal method for
      uncovering and understanding the deregulated cellular processes driving tumor
      initiation and progression. Whole-genome sequencing is evolving toward becoming
      less costly and more feasible on a large scale; consequently, thousands of tumors
      are being analyzed with these technologies. Interpreting these data in the
      context of tumor complexity poses a challenge for cancer genomics. CONTENT: The
      sequencing of large numbers of tumors has revealed novel insights into oncogenic
      mechanisms. In particular, we highlight the remarkable insight into the
      pathogenesis of breast cancers that has been gained through comprehensive and
      integrated sequencing analysis. The analysis and interpretation of sequencing
      data, however, must be considered in the context of heterogeneity within and
      among tumor samples. Only by adequately accounting for the underlying complexity
      of cancer genomes will the potential of genome sequencing be understood and
      subsequently translated into improved management of patients. SUMMARY: The
      paradigm of personalized medicine holds promise if patient tumors are thoroughly
      studied as unique and heterogeneous entities and clinical decisions are made
      accordingly. Associated challenges will be ameliorated by continued collaborative
      efforts among research centers that coordinate the sharing of mutation,
      intervention, and outcomes data to assist in the interpretation of genomic data
      and to support clinical decision-making.

PMID- 23151420
TI  - Quantum dots shed light on diagnoses.

PMID- 23151422
TI  - Ultrasound visual image-guided vs Doppler auditory-assisted radial artery
      cannulation in infants and small children by non-expert anaesthesiologists: a
      randomized prospective study.
AB  - BACKGROUND: Cannulation of the radial artery in infants and small children can be
      challenging, even for the most experienced providers. Utilizing Doppler to aid in
      radial artery cannulation has been well described. Recent studies have
      demonstrated the efficacy of ultrasound (US) image-guided vascular access
      techniques in the paediatric population. The utility of these two techniques,
      when used by non-expert personnel, has not been studied. METHODS: This is a
      randomized prospective study to compare the utility of two different radial
      arterial cannulation techniques in paediatric patients weighing <12 kg: US-guided
      technique (US group) vs Doppler-assisted technique (Doppler group) when used by
      trainees with limited experience. The primary objective was to compare the first
      attempt success rate between each group. As a secondary objective, success rate
      within 10 min was compared. RESULTS: The trial was prematurely terminated after
      50% of paediatric patients (n=104) were included in the study and 52 of each were
      randomized to the US or Doppler group. A total of 12 anaesthesia trainees
      performed radial arterial cannulations. The first-attempt success rate was
      greater in the US group compared with the Doppler group [17/52 (33%) vs 8/52
      (15%), P=0.039, odds ratio (OR): 2.67, confidence interval (CI): 1.03-6.91]. The
      overall success rate within 10 min was 34/52 (65%) in the US group and 24/52
      (46%) in the Doppler group (P=0.048, OR: 2.20, CI: 1.00-4.85). CONCLUSIONS: US
      guided radial arterial cannulation in infants and small children provided a
      greater chance for success at the first attempt compared with the Doppler
      assisted technique.

PMID- 23151421
TI  - Combined paravertebral and intrathecal vs thoracic epidural analgesia for post
      thoracotomy pain relief.
AB  - BACKGROUND: Although thoracic epidural analgesia (TEA) is considered the gold
      standard for post-thoracotomy pain relief, thoracic paravertebral block (PVB) and
      intrathecal opioid (ITO) administration have also been shown to be efficacious.
      We hypothesized that the combination of PVB and ITO provides analgesia comparable
      with that of TEA. METHODS: After local ethics committee approval, 84 consecutive
      patients undergoing open thoracic procedures were randomized to the TEA
      (ropivacaine 0.2%+sufentanil) or the PVB (ropivacaine 0.5%)+ITO
      (sufentanil+morphine) group. The primary endpoints were pain intensities at rest
      and during coughing/movement at 1, 2, 4, 8, 12, 24, 48, and 72 h after operation
      assessed by visual analogue scale (VAS) score. Data were analysed by multivariate
      analysis (anova; P<0.05). RESULTS: Patient and surgical characteristics were
      comparable between the groups. The mean and maximal VAS scores were lower in the
      TEA (n=43) than in the PVB+ITO group (n=37) at several time points at rest
      (P<0.026) and during coughing/movement (P<0.021). However, in the PVB+ITO group,
      the mean VAS scores never exceeded 1.9 and 3.5 at rest and during
      coughing/movement, respectively; and the maximal differences between the groups
      (TEA vs PVB+ITO) in the maximal VAS scores were only 1.2 (3.4 vs 4.6) at rest,
      and 1.3 (4.4 vs 5.7) during coughing/movement. CONCLUSIONS: Although VAS scores
      were statistically lower in the TEA compared with the PVB+ITO group at some
      observation points, the differences were small and of questionable clinical
      relevance. Thus, combined PVB and ITO can be considered a satisfactory
      alternative to TEA for post-thoracotomy pain relief. ClinicalTrials.gov number.
      NCT00493909.

PMID- 23151423
TI  - Weekly topotecan and cisplatin (TOPOCIS) as neo-adjuvant chemotherapy for locally
      advanced squamous cervical carcinoma: Results of a phase II multicentric study.
AB  - OBJECTIVES: The aim of this phase II multicentric study was to evaluate the
      efficacy and toxicity of neo-adjuvant chemotherapy with weekly topotecan and
      cisplatin in locally-advanced squamous cervical cancer. PATIENTS AND METHODS:
      From November 2008 to January 2011, 92 patients met the inclusion criteria and
      were enrolled. Eligibility criteria were: squamous or adenosquamous cervical
      cancer; clinical stages IB2, IIA, IIB; Eastern Cooperative Oncology Group (ECOG)
      Performance Status (PS)<= 2; neutrophils >=1500/MUL; platelets >=100,000/MUL,
      normal renal and liver function. Treatment consisted of six courses of weekly
      topotecan (2mg/m(2)) and cisplatin (40 mg/m(2)). All responsive and stable
      patients were submitted to radical surgery, while progressed cases underwent
      definitive radiotherapy+/-chemotherapy. Primary end-point was evaluation of
      efficacy and toxicity. All patients are evaluable for toxicity and efficacy.
      RESULTS: Ninety-six percent of patients completed the six planned courses of
      chemotherapy, and 95% of courses were administered at a full dose and without
      interruption or delay. Mean age was 49 years (35-64 years). FIGO Stage
      distribution was 30 IB2, 13 IIA and 49 IIB. Treatment was well tolerated and no
      death occurred. G3-G4 haematological toxicity was observed in 28% of patients (5%
      out of cycles). Support therapies (blood transfusions and/or erythropoietin
      and/or Granocyte-Colony Stimulating Factor) were given to 24% of patients.
      Clinical response rate was 77%. The nine progressed cases were irradiated, while
      the remaining 83 patients were submitted to radical surgery. An overall
      pathologic response was observed in 67% of patients, with an optimal response
      rate of 32% and a disease downstage in 57% of patients. Nodal metastases occurred
      in 36% of patients. Adjuvant therapy (radiotherapy and or chemotherapy) was
      prescribed in 55% of patients, because of lymph node metastases, parametrial or
      vaginal involvement or cut-through margins. Median follow-up was 18 months: 76%
      of patients are alive and free from recurrence, 24% of patients relapsed and 13%
      died. CONCLUSIONS: Weekly topotecan and cisplatin showed an acceptable toxicity
      profile; the promising response rate warrants further investigation.

PMID- 23151424
TI  - Frequency and clinical correlates of retrocollis in Parkinson's disease.
AB  - PURPOSE: To investigate the incidence of retrocollis and to determine its
      clinical correlates in patients with idiopathic Parkinson's disease (PD).
      METHODS: Seventy-four patients with PD at Hoehn and Yahr stage 5 were examined
      for abnormal neck postures and were classified according to neck posture.
      Differences in age, age at PD onset, disease duration, years from PD onset to
      Hoehn and Yahr stage 5, cognitive state, the levodopa equivalent dose (LED) for
      dopaminergic drugs, and rigidity of the neck and upper and lower extremities were
      examined to determine the clinical correlates of abnormal neck posture. We also
      evaluated retrocollis in 356 patients with PD at Hoehn and Yahr stage 1, 2, 3,
      and 4 and 65 age matched normal controls. RESULTS: Of the 74 patients with PD at
      Hoehn and Yahr stage 5 examined, 21 (28.4%) had retrocollis, 3 (4.1%) had
      antecollis, and 1 (1.4%) had antecollis and torticollis. Whereas, only one
      patient had retrocollis in PD patients at Hoehn and Yahr stage 4 and under.
      Patients with antecollis were significantly younger than those with normal neck
      posture and retrocollis. There were no differences in age at PD onset, disease
      duration, sex, years from PD motor symptom onset to Hoehn and Yahr stage 5,
      cognitive state, or LED between patients with and without abnormal neck postures.
      Neck rigidity scores were significantly higher in patients with retrocollis and
      antecollis than in those with normal neck posture. CONCLUSIONS: Retrocollis is
      not rare in patients with PD at Hoehn and Yahr stage 5, and the incidence
      appeared to increase as axial rigidity increased.

PMID- 23151426
TI  - Motor cortex stimulation modulates defective central beta rhythms in patients
      with neuropathic pain.
AB  - OBJECTIVE: Motor cortex stimulation therapy (MCS) is increasingly used to control
      refractory neuropathic pain. Post-movement beta synchronization (PMBS) is defined
      as a sharp increase in beta-frequency electroencephalographic power following
      movement offset and may reflect sensorimotor cortex inhibition induced, at least
      in part, by cortical processing of movement-related sensory afferent inputs. PMBS
      pattern is then often altered in case of neuropathic pain. The main objective of
      the present study was to test the hypothesis that implanted MCS modulates PMBS in
      patients presenting with neuropathic pain. METHODS: Using a high-resolution, 128
      electrode electroencephalographic system, we recorded and compared, before and
      during MCS, PMBS patterns during brisk, unilateral right and left index finger
      extension in 8 patients presenting with neuropathic pain. RESULTS: The pre
      operative PMBS patterns were altered in all cases. MCS increased the spatial
      distribution and amplitude of PMBS in most of cases and restored maximum
      intensity of PMBS contralateral to the painful body side. These modifications
      appeared significantly correlated with the analgesic effect of MCS. CONCLUSION:
      This study provides evidence of central beta rhythms neuromodulation induced by
      MCS. SIGNIFICANCE: The restoration by MCS of defective cortical inhibition in
      patients with neuropathic pain is evoked.

PMID- 23151425
TI  - Benign course of tumour-like multiple sclerosis. Report of five cases and
      literature review.
AB  - BACKGROUND: Multiple sclerosis (MS) with initial neuroradiological features
      suggestive of brain tumour (tumour-like MS) may represent a challenging
      diagnosis. METHODS: Among the patients seen at the MS centre of our Institution
      between 2000 and 2010, we identified cases presenting with a large (diameter>2
      cm), well-defined lesion, suggestive of brain tumour on initial brain magnetic
      resonance imaging (MRI). Only patients with at least 10 years follow-up were
      included. RESULTS: Five young women with MS who presented with a tumour-like
      lesion on initial brain MRI are described. All cases presented with sudden-onset
      neurological deficits due to a single large brain lesion compatible with neoplasm
      at MRI. Two cases underwent brain stereotactic biopsy, both misdiagnosed as
      astrocytoma. However, the subsequent clinical and MRI follow-up was consistent
      with MS in all cases. Unnecessary surgery and radiotherapy were responsible for
      disability in two cases. In three cases, the course of the disease remains benign
      after more than 13 years from symptoms onset. CONCLUSIONS: Our report of
      clinical, radiological and pathological features of five tumour-like MS cases
      confirms that it is mandatory to consider a demyelinating process in the
      differential diagnosis of tumour-like brain lesions. Many tumour-like MS cases
      may have a favourable long term prognosis.

PMID- 23151427
TI  - Changes in body mass in later life and incident dementia.
AB  - BACKGROUND: There is ongoing debate about whether a decline in body mass
      represents a true risk factor for dementia, whether it is a phenotypic marker of
      incipient dementia, or perhaps a marker of another process that increases
      dementia risk. This study was designed to determine if changes in body mass index
      (BMI) in later life are associated with hazard of incident dementia over a follow
      up period of up to eight years. METHODS: Method followed was a prospective cohort
      study of 4,181 men aged 65-84 years, resident in Perth, Australia. The exposure
      of interest was change in BMI measured between 1996-1998 and 2001-2004. The
      outcome was incident dementia, established using the Western Australia Data
      Linkage System until 2009. We used Cox regression models to establish crude and
      adjusted hazard of dementia for change in BMI. RESULTS: Compared with men with a
      stable BMI, those with a decrease in BMI >1 kg/m2 had a higher adjusted hazard of
      dementia (hazard ratio (HR) = 1.89, 95% CI = 1.32-2.70). The cumulative hazard of
      dementia over follow-up for changes in BMI was greatest for men with a decrease
      in BMI >1 kg/m2; this trend was apparent for men in all BMI categories
      (underweight, normal, overweight, obese). A reverse "J-shaped" association
      between BMI change and incident dementia was observed, with the lowest dementia
      rate being for men whose BMI remained stable. CONCLUSIONS: Men who maintained a
      stable body mass had the lowest incidence of dementia. Further studies are needed
      to clarify causality and assess feasibility of interventional studies to preserve
      body mass in aging men.

PMID- 23151428
TI  - Comparison of bilateral pulse arrival time before and after induced vasodilation
      by axillary block.
AB  - The propagation time of arterial pulse waves provides information about arterial
      stiffness. Pulse arrival time (PAT) is calculated as the time between the R-wave
      (ECG) and three reference points on photoplethysmographic (PPG) pulse waves:
      foot, first derivative and peak. Because large variation in PAT-values between
      patients exists, measurements of the contra-lateral arm as reference could be a
      solution. However, anatomical differences between arteries of the arms could
      introduce an offset of PAT. Furthermore, when arterial stiffness decreases (e.g.
      after axillary blockade (AxB)) and pulse wave amplitude increases (vasodilation),
      the pulse waveform can change. The aim of this study was to investigate whether
      there is a difference between the PAT of both arms and to evaluate the effect of
      vasodilation after AxB on PAT. ECG and PPG was measured on both hands in 34
      patients, starting 2 min before the injection of local anaesthetic of an AxB and
      continuing for a period of 30 min after block placement. PAT of the baseline and
      after AxB were calculated and compared. The mean-PAT of both arms were not
      significantly different for the three reference points. After AxB, PAT
      significantly increased for all reference points. PAT can be used for intra
      subject comparison.

PMID- 23151429
TI  - Molecular hybridization of bioactives: synthesis and antitubercular evaluation of
      novel dibenzofuran embodied homoisoflavonoids via Baylis-Hillman reaction.
AB  - A novel series of natural product like dibenzofuran embodied homoisoflavonoids
      [(E)-3-(dibenzo[b,d]furan-2-ylmethylene)chroman-4-ones] designed by molecular
      hybridization were synthesized in very good yields via a sequence of reactions
      involving base catalyzed Baylis-Hillmann (BH) reaction of 2-dibenzofuran
      carboxaldehyde and methyl acrylate; bromination of BH adduct; condensation of
      resulted allylic bromide with substituted phenols or 2-dibenzofuranol followed by
      cyclization. Among the all 11 new compounds screened for in vitro
      antimycobacterial activity against Mycobacterium tuberculosis H37Rv (MTB), (E)-3
      (dibenzo[b,d]furan-2-ylmethylene)-6-fluorochroman-4-one (7f) and (E)-3
      (dibenzo[b,d] furan-2-ylmethylene)-6-fluorochroman-4-one (7 g) were found to be
      active with MIC 12.5 MUg/mL.

PMID- 23151430
TI  - Harms versus benefits with duration of androgen suppression.

PMID- 23151431
TI  - Quality of life in men with locally advanced prostate cancer treated with
      leuprorelin and radiotherapy with or without zoledronic acid (TROG 03.04 RADAR):
      secondary endpoints from a randomised phase 3 factorial trial.
AB  - BACKGROUND: Adjuvant androgen suppression and bisphosphonates with escalating
      doses of radiotherapy might improve efficacy outcomes in men with locally
      advanced prostate cancer. In this study, we investigated whether these treatments
      had a detrimental effect on patient-reported-outcome (PRO) scores. METHODS: We
      undertook a phase 3 trial with a 2*2 factorial design in 23 centres in Australia
      and New Zealand in men with non-metastatic adenocarcinoma of the prostate (stage
      T2b-4 or T2a, Gleason score >=7, and baseline prostate-specific antigen
      concentration [PSA] >=10 MUg/L), and without previous lymph node or systemic
      metastases or comorbidities that could reduce life expectancy to less than 5
      years. The men were randomly assigned in a 1:1:1:1 ratio to 6 months of
      neoadjuvant (short-term) androgen suppression (STAS) with leuprorelin (22.5 mg
      every 3 months, intramuscularly) or an additional 12 months (intermediate-term
      androgen suppression [ITAS]) of leuprorelin with or without 18 months of
      zoledronic acid (4 mg every 3 months, intravenously). Study drug administration
      commenced at randomisation after which radiotherapy started within the fifth
      month in all groups. Treatment allocation was open-label, and computer-generated
      randomisation, stratified by centre, baseline concentrations of PSA, clinical
      stage of the tumour, Gleason score, and use of a brachytherapy boost, was done by
      use of the minimisation technique. PRO scores were calculated from European
      Organization for Research and Treatment of Cancer quality-of-life and prostate
      specific quality-of-life module questionnaires and compared with multiple
      regression models at baseline, and end of radiotherapy, and 18 months and 36
      months according to group and radiation dose. The trial is ongoing and the
      primary endpoint, prostate-cancer-specific mortality, will be reported in 2014.
      This study is the final report of PRO scores (a secondary endpoint). Analysis was
      by intention to treat. This trial is registered with ClinicalTrials.gov, number
      NCT00193856. FINDINGS: 1071 men were randomly assigned to STAS (n=268), STAS plus
      zoledronic acid (n=268), ITAS (n=268), and ITAS plus zoledronic acid (n=267). At
      the end of radiotherapy, significant detrimental changes in PRO scores (p<0.01)
      occurred in all groups. There were no significant differences in global health
      status between groups at any timepoint. At 18 months, PROs that were
      significantly worse in the ITAS groups when compared with STAS were hormone
      treatment-related symptoms (HTRS; STAS, 10.20 [95% CI 8.66-11.75]; ITAS, 17.36
      [13.63-21.08], p<0.01; and ITAS plus zoledronic acid, 19.14 [15.43-22.85],
      p<0.01), sexual activity (STAS, 26.38 [23.50-29.27]; ITAS, 14.40 [7.44-21.36],
      p<0.01; and ITAS plus zoledronic acid, 16.34 [9.39-23.28], p<0.01), social
      function (STAS, 90.31 [87.89-92.73]; ITAS, 87.35 [81.52-93.18], p=0.09; and ITAS
      plus zoledronic acid, 83.66 [77.85-89.48], p<0.01), fatigue (STAS, 17.05 [14.58
      19.51]; ITAS 24.52 [18.58-30.46], p<0.01; and ITAS plus zoledronic acid, 24.26
      [18.33-30.18], p<0.01), and financial problems (STAS, 3.39 [1.29-5.48]; ITAS,
      8.97 [3.92-14.02], p<0.01; and ITAS plus zoledronic acid, 8.92 [3.89-13.96],
      p<0.01). With the exception of HTRS, in which marginal differences remained,
      persisting significant differences disappeared by 36 months. Other factors
      associated with significant detrimental changes in PRO scores were a
      brachytherapy boost, incomplete testosterone and haemoglobin recoveries, age, and
      smoking. INTERPRETATION: Compared with 6 months of androgen suppression, 18
      months of androgen suppression causes additional detrimental changes at the 18
      month follow-up in some PRO scores but not in global quality-of-life scores.
      However, with the exception of HTRS, these differences resolved by 36 months. The
      use of zoledronic acid every 3 months over 18 months does not result in
      additional detrimental changes, but the use of a brachytherapy boost to achieve
      radiation dose escalation in the prostate can adversely affect emotional function
      and financial problems. FUNDING: National Health and Medical Research Council of
      Australia, Novartis Pharmaceuticals Australia, Abbott Pharmaceuticals Australia,
      New Zealand Health Research Council, New Zealand Cancer Society, University of
      Newcastle (Australia), Hunter Medical Research Institute, Calvary Mater Radiation
      Oncology Fund, and Maitland Cancer Appeal.

PMID- 23151432
TI  - Keeping active channels in their place: membrane phosphoinositides regulate TRPM
      channel activity in a compartment-selective manner.
AB  - We have long appreciated that the controlled movement of ions and solutes across
      the cell surface or plasma membrane affects every aspect of cell function,
      ranging from membrane excitability to metabolism to secretion, and is also
      critical for the long-term maintenance of cell viability. Studies examining these
      physiological transport processes have revealed a vast array of ion channels,
      transporters and ATPase-driven pumps that underlie these transmembrane ionic
      movements and how acquired or genetic disruption of these processes are linked to
      disease. More recently, it has become evident that the ongoing function of
      intracellular organelles and subcellular compartments also depends heavily on the
      controlled movement of ions to establish distinct pH or ionic environments.
      However, limited experimental access to these subcellular domains/structures has
      hampered scientific progress in this area, due in large part to the difficulty of
      applying proven functional assays, such as patch clamp and radiotracer
      methodologies, to these specialized membrane locations. Using both functional and
      immune-labeling assays, we now know that the types and complement of channels,
      transporters and pumps located within intracellular membranes and organelles
      often differ from those present on the plasma membrane. Moreover, it appears that
      this differential distribution is due to the presence of discrete tags/signals
      present within these transport proteins that dictate their sorting/trafficking to
      spatially discrete membrane compartments, where they may also interact with
      scaffolding proteins that help maintain their localization. Such targeting
      signals may thus operate in a manner analogous to the way a postal code is used
      to direct the delivery of a letter.

PMID- 23151433
TI  - A new device concept for directly modulating spinal cord pathways: initial in
      vivo experimental results.
AB  - We describe a novel spinal cord (SC) stimulator that is designed to overcome a
      major shortcoming of existing stimulator devices: their restricted capacity to
      selectively activate targeted axons within the dorsal columns. This device
      overcomes that limitation by delivering electrical stimuli directly to the pial
      surface of the SC. Our goal in testing this device was to measure its ability to
      physiologically activate the SC and examine its capacity to modulate
      somatosensory evoked potentials (SSEPs) triggered by peripheral stimulation. In
      this acute study on adult sheep (n = 7), local field potentials were recorded
      from a grid placed in the subdural space of the right hemisphere during
      electrical stimulation of the left tibial nerve and the spinal cord. Large
      amplitude SSEPs (>200 uV) in response to SC stimulation were consistently
      obtained at stimulation strengths well below the thresholds inducing neural
      injury. Moreover, stimulation of the dorsal columns with signals employed
      routinely by devices in standard clinical use, e.g., 50 Hz, 0.2 ms pulse width,
      produced long-lasting changes (>4.5 h) in the SSEP patterns produced by
      subsequent tibial nerve stimulation. The results of these acute experiments
      demonstrate that this device can be safely secured to the SC surface and
      effectively activate somatosensory pathways.

PMID- 23151434
TI  - A novel Notch3 deletion mutation in a Chinese patient with cerebral autosomal
      dominant arteriopathy with subcortical infarcts and leucoencephalopathy
      (CADASIL).
AB  - Cerebral autosomal dominant arteriopathy with subcortical infarcts and
      leucoencephalopathy (CADASIL) is a rare autosomal dominant hereditary
      cerebrovascular disease characterised by migraine attacks, recurrent subcortical
      transient ischemic attacks or strokes, cognitive decline, and dementia. It is
      caused by mutations in the Notch3 gene on chromosome 19p13.1, which is the only
      gene currently known to be closely associated with CADASIL. We describe a novel
      100 base pair base fragment deletion mutation (ENST 00000263388, c.512-611del) in
      the Notch3 gene from a Chinese patient with CADASIL. The present patient has the
      characteristic clinical and family history for CADASIL, which suggests that
      C.512del611 may be a cause of CADASIL as well as most of the previously reported
      Notch3 mutations.

PMID- 23151435
TI  - E. Graeme Robertson--dynamics in fluid and light.
AB  - An eponymous lecture at the Australian and New Zealand Association of
      Neurologists Annual Scientific Meeting commemorates E. Graeme Robertson (1903
      75), and some neurologists will know that particular Australian practices in
      clinical neurology, so far as they exist, have origins in his career. This is a
      historical article on the literary record of a man who had his own sense of
      history--an affinity with the past as well as an awareness of future generations
      of readers. He wrote authoritative texts on pneumoencephalography before new
      technology made it obsolete, and he produced a series of books on decorative
      architectural cast iron in Australian cities. A talent for visual interpretation
      seems to have drawn him to both of these topics; a common theme is contrast
      between light and dark, which is expatiated in images and in clear, well-written
      prose in his publications. We review his medical writings, including some largely
      forgotten principles of cerebrospinal fluid physics that he discovered when
      researching pneumoencephalography. We also explore his obsession with cast iron-
      its architectural historical significance, his techniques for photographing it,
      and some of the ways that it related to his life's work as a clinical
      neurologist.

PMID- 23151436
TI  - Genetic association study of glucocerebrosidase gene L444P mutation in essential
      tremor and multiple system atrophy in mainland China.
AB  - The glucocerebrosidase (GBA) gene mutation is emerging as an important risk
      factor for Parkinson's disease. We previously reported that the GBA gene L444P
      mutation is an important risk factor for PD in the Chinese population. The
      prevalence of this mutation in other neurodegenerative diseases and movement
      disorders remains completely unexplored in mainland China. In the present study,
      we extended the screening of GBA gene L444P mutation to Chinese patients with
      essential tremor (ET) and multiple system atrophy (MSA). We searched for the GBA
      gene L444P mutation in 109 patients with ET, 54 patients with MSA, and 657
      controls from mainland China. None of the 109 patients with ET or 54 patients
      with MSA carried the GBA gene L444P mutation. Among the 657 controls, we found
      one L444P heterozygote. The difference in mutation frequencies between patients
      with ET or MSA and the control group was not statistically significant (chi
      squared test, p = 1, respectively). The results suggest that the GBA gene L444P
      mutation may be not responsible for ET in mainland China. Whether the GBA gene
      L444P mutation modifies the risk for MSA deserves further study in larger
      samples.

PMID- 23151437
TI  - Measurement of insulin-mediated glucose uptake: direct comparison of the modified
      insulin suppression test and the euglycemic, hyperinsulinemic clamp.
AB  - BACKGROUND: Two direct measurements of peripheral insulin sensitivity are the M
      value derived from the euglycemic, hyperinsulinemic clamp (EC) and the steady
      state plasma glucose (SSPG) concentration derived from the insulin suppression
      test (IST). Prior work suggests that these measures are highly correlated, but
      the agreement between them is unknown. To determine the agreement between SSPG
      and M and to develop transformation equations to convert SSPG to M and vice
      versa, we directly compared these two measurements in the same individuals.
      METHODS: A total of 15 nondiabetic subjects (9 women and 6 men) underwent both an
      EC and a modified version of the IST within a median interval of 5days. We
      performed standard correlation metrics of the two measures and developed
      transformation regression equations for the two measures. RESULTS: The mean+/-SD
      age of the subjects was 57+/-7years and body mass index, 27.7+/-3.9kg/m(2). The
      median (interquartile range) SSPG concentration was 6.7 (5.1, 9.8) mmol/L and M
      value, 49.6 (28.9, 64.2) MUmol/min/kg-LBM. There was a highly significant
      correlation between SSPG and M (r=-0.87, P <0.001). The relationship was best fit
      by regression models with exponential/logarithmic functions (R(2)=0.85). Bland
      Altman plots demonstrated an excellent agreement between these measures of
      insulin action. CONCLUSION: The SSPG and M are highly related measures of insulin
      sensitivity and the results provide the means to directly compare the two
      measurements.

PMID- 23151439
TI  - Restenosis after carotid endarterectomy and stenting--authors' reply.

PMID- 23151438
TI  - The effect of varying ratios of docosahexaenoic acid and arachidonic acid in the
      prevention and reversal of biochemical essential fatty acid deficiency in a
      murine model.
AB  - OBJECTIVE: Essential fatty acids (EFA) are necessary for growth, development, and
      biological function, and must be acquired through the diet. While linoleic acid
      (LA) and alpha-linolenic acid (ALA) have been considered the true EFAs, we
      previously demonstrated that docosahexaenoic acid (DHA) and arachidonic acid (AA)
      taken together as the sole source of dietary fatty acids can prevent biochemical
      essential fatty acid deficiency (EFAD). This study evaluates the effect of
      varying dietary ratios of DHA:AA in the prevention and reversal of biochemical
      EFAD in a murine model. METHODS: Using a murine model of EFAD, we provided mice
      with 2.1% of daily caloric intake in varying DHA:AA ratios (1:1, 5:1, 10:1, 20:1,
      200:1, 100:0) for 19 days in association with a liquid high-carbohydrate fat-free
      diet to evaluate the effect on fatty acid profiles. In a second experiment, we
      evaluated the provision of varying DHA:AA ratios (20:1, 200:1, 100:0) on the
      reversal of biochemical EFAD. RESULTS: Mice provided with DHA and AA had no
      evidence of biochemical EFAD, regardless of the ratio (1:1, 5:1, 10:1, 20:1,
      200:1, 100:0) administered. Biochemical EFAD was reversed with DHA:AA ratios of
      20:1, 200:1, and 100:0 following 3 and 5 weeks of dietary provision, although the
      20:1 ratio was most effective in the reversal and stabilization of the
      triene:tetraene ratio. CONCLUSION: Provision of DHA and AA, at 2.1% of daily
      caloric intake in varying ratios can prevent biochemical evidence of EFAD and
      hepatic steatosis over the short-term, with a ratio of 20:1 DHA:AA most
      effectively reversing EFAD.

PMID- 23151440
TI  - Restenosis after carotid endarterectomy and stenting.

PMID- 23151441
TI  - Situs inversus totalis and congenital hypoglossia associated with atrial ectopic
      bradycardia and normal neurodevelopmental outcome.

PMID- 23151442
TI  - Steady-state indicators of the intracranial pressure dynamic system using
      geodesic distance of the ICP pulse waveform.
AB  - Normal functioning of the brain depends on the homeostasis (~ steady state) of
      its various physiological sub-systems, one of which is the intracranial pressure
      (ICP) dynamic system. The ICP dynamic system of an injured brain is susceptible
      to various acute changes that should ideally be detected by ICP monitoring even
      for comatose patients. However, the status quo of ICP monitoring solely targets
      mean ICP. We aimed to demonstrate a novel approach to detect acute deviation from
      steady state of an ICP dynamic system in an absence of significant mean ICP
      changes. We hypothesized that steady state of ICP dynamic systems is reflected as
      ICP pulses of similar mean ICP levels resembling each other for a given subject.
      A general framework was used to derive such a steady-state indicator that can
      accommodate different metrics of inter-pulse distance and different statistics of
      the distance histograms. In addition to conventional Euclidean distance and
      Pearson correlation, geodesic distance between pulses was introduced as a novel
      metric. These different ways of calculating steady-state indicators under the
      proposed framework were evaluated on three types of continuous ICP recordings:
      (1) those between two consecutive brain imaging studies that demonstrated acute
      ventricular enlargement for slit ventricle syndrome (SVS) patients undergoing a
      trial of shunt externalization and clamping (SVS+); (2) those between consecutive
      brain imaging studies from the SVS patients under the same trial but without
      ventricular enlargement (SVS-); (3) overnight recordings from normal pressure
      hydrocephalus (NPH) patients. It was observed that only the standard deviation of
      geodesic distance correctly differentiated between SVS+ and SVS- and between SVS+
      and NPH while avoiding discriminating between SVS- and NPH. It was also found
      that 45% SVS+ cases had a multimodal geodesic distance histogram while none of
      SVS- and 3.8% of NPH cases had such a multimodal histogram. Pulses with a large
      number of distant pulses for the five multimodal-histogram SVS+ cases fell in
      short time windows indicating that acute ventricular changes may have occurred in
      these confined time windows during which no significant changes of mean ICP were
      observed. In contrast, the pulses with a large number of distant pulses for the
      two multimodal-histogram NPH cases did not cluster temporally. In conclusion, the
      geodesic inter-pulse distance is a promising metric to quantify distance
      intrinsic to the underneath geometric structure of ICP signals and hence is a
      more suitable way to derive a steady-state indicator of an ICP dynamic system.

PMID- 23151443
TI  - Human vaccines: news.

PMID- 23151445
TI  - Letter from the editor.

PMID- 23151446
TI  - Electrogenetherapy of B16.F10 murine melanoma tumors with an interleukin-28
      expressing DNA plasmid.
AB  - Augmented delivery of cytokine-expressing DNA plasmids to subcutaneous tumors has
      been demonstrated to result in a level of enhanced anti-tumor activity. One
      delivery enhancement method which has been evaluated is in vivo electroporation
      (EP), a contact-dependent delivery technique where electric pulses are
      hypothesized to augment the transfer of DNA into cells and tissues through the
      induction of temporary cell membrane pores. Previous work by members of our
      group, as well as others, has demonstrated the anti-tumor effects of DNA plasmids
      expressing the cytokines IL-12 and IL-15. In this report the potential anti-tumor
      activity of a relatively newly-described cytokine, IL-28, was measured when
      administered intratumorally as a DNA expression plasmid (designated pIL28) to
      established murine (B16.F10) melanoma tumors. The administration of the IL-28
      expressing plasmid was performed through enhanced delivery methods. One method
      was EP and the other a non-contact dependent technique using a helium plasma
      stream. IL-28 is a member of the type III interferon family of cytokines that has
      been characterized as possessing potent anti-viral activity. This cytokine has
      been demonstrated to function as an adjuvant in small animal model vaccination
      protocols and stimulates CD8+ CTL responses. In addition, stimulation of anti
      tumor activity has been demonstrated in several studies using IL-28. Based on
      these activities, it was hypothesized that this cytokine could, when delivered
      through a DNA expression plasmid, mediate anti-tumor activity. The results of
      this study indicated that enhanced delivery of pIL-28 resulted in attenuation of
      tumor growth, compared with non-enhanced delivery. Of note, this is the first
      proof-of-concept experiment, of our knowledge, documenting the ability of a non
      contact dependent helium plasma-based delivery method to mediate the enhancement
      of an anti-tumor effect by a cytokine-expressing DNA plasmid. This suggests the
      use of the helium plasma delivery method as an alternative or adjunctive method
      to EP for the effective delivery of agents that possess potential anti-tumor
      activity.

PMID- 23151447
TI  - Plasmid IL-12 electroporation in melanoma.
AB  - Intratumoral gene electroporation uses electric charges to facilitate entry of
      plasmid DNA into cells in a reproducible and highly efficient manner, especially
      to accessible sites such as cutaneous and subcutaneous melanomas. Effective for
      locally treated disease, electroporation of plasmid DNA encoding interleukin-12
      can also induce responses in untreated distant disease, suggesting that adaptive
      immune responses are being elicited that can target melanoma-associated antigens.
      In vivo electroporation with immunomodulatory cytokine DNA is a promising
      approach that can trigger systemic anti-tumor immune responses without the
      systemic toxicity associated with intravenous cytokine delivery and potentially
      offer complete long-term tumor regression.

PMID- 23151448
TI  - Vaccination with synthetic constructs expressing cytomegalovirus immunogens is
      highly T cell immunogenic in mice.
AB  - There is no licensed vaccine or cure for human cytomegalovirus (CMV), a
      ubiquitous beta-herpesvirus infecting 60-95% of adults worldwide. Infection can
      cause congenital abnormalities, result in severe disease in immunocompromised
      patients, and is a major impediment during successful organ transplantation. In
      addition, it has been associated with numerous inflammatory diseases and cancers,
      as well as being implicated in the development of essential hypertension, a major
      risk factor for heart disease. To date, limited data regarding the identification
      of immunogenic viral targets has frustrated CMV vaccine development. Based upon
      promising clinical data suggesting an important role for T cells in protecting
      against disease in the transplantation setting, we designed a novel panel of
      highly-optimized synthetic vaccines encoding major CMV proteins and evaluated
      their immune potential in murine studies. Vaccination induced robust CD8+ and
      CD4+ T cells of great epitopic breadth as extensively analyzed using a novel
      modified T cell assay described herein. Together with improved levels of CMV
      specific T cells as driven by a vaccine, further immune evaluation of each target
      is warranted. The present model provides an important tool for guiding future
      immunization strategies against CMV.

PMID- 23151449
TI  - Pilot study on the immunogenicity of paired Env immunogens from mother-to-child
      transmitted HIV-1 isolates.
AB  - Recent studies have reported that founder viruses play unique roles in
      establishing HIV-1 infection. Understanding the biological and immunological
      features of envelope glycoproteins (Env) from such viruses may facilitate the
      development of effective vaccines against HIV-1. In this report, we evaluated the
      immunogenicity of gp120 immunogens from two pairs of clade B and two pairs of
      clade C mother-to-child transmitted (MTCT) HIV-1 variants that had various levels
      of sensitivity to broadly neutralizing monoclonal antibodies. Individual gp120
      DNA and protein vaccines were produced from each of the eight MTCT Env antigens
      included in the current study. Rabbits were immunized with these gp120 immunogens
      by the DNA prime-protein boost approach. High level Env-specific antibody
      responses were elicited by all MTCT gp120 immunogens. However, their abilities to
      elicit neutralizing antibody (NAb) responses differed and those from relatively
      neutralization-resistant variants tended to be more effective in eliciting
      broader NAb. Results of this pilot study indicated that not all MTCT Env proteins
      have the same potential to elicit NAb. Understanding the mechanism(s) behind such
      variation may provide useful information in formulating the next generation of
      HIV vaccines.

PMID- 23151450
TI  - Electroporation driven delivery of both an IL-12 expressing plasmid and cisplatin
      synergizes to inhibit B16 melanoma tumor growth through an NK cell mediated tumor
      killing mechanism.
AB  - Combined therapy using chemotherapeutic drugs and immunotherapeutics offers some
      promise for treating patients with cancer. In this study, we evaluated whether
      cisplatin delivered by intratumoral (IT)-electroporation (EP) might enhance
      antitumor activity against established B16 melanoma and whether further addition
      of intramuscular (IM)-EP of IL-12 cDNA to IT-EP of cisplatin might augment
      antitumor therapeutic activity, with a focus on the underlining antitumor
      mechanism(s). When tumor (7 mm)-bearing animals were treated locally with
      cisplatin by IT-EP, they showed tumor growth inhibition significantly more than
      those without IT-EP. Moreover, IL-12 cDNA delivered by IM-EP was also able to
      inhibit tumor growth significantly more than control vector delivery. This tumor
      growth inhibition was mediated by NK cells, but not CD4+ T or CD8+ T cells, as
      determined by immune cell subset depletion and IFN-gamma induction. Moreover,
      concurrent therapy using IT-EP of cisplatin plus IM-EP of IL-12 cDNA displayed
      antitumor therapeutic synergy. This therapeutic synergy appeared to be mediated
      by increased sensitivity of cisplatin-treated tumors to NK cell-mediated tumor
      killing. Taken together, these data support that cisplatin delivery by IT-EP plus
      IL-12 gene delivery by IM-EP are more effective at inducing antitumor therapeutic
      responses through increased sensitivity of cisplatin-treated tumors to NK cell
      mediated tumor killing. This combined approach might have some implication for
      treating melanoma in patients.

PMID- 23151452
TI  - Sequential administration of cytokine genes to enhance cellular immune responses
      and CD4 (+) T memory cells during DNA vaccination.
AB  - Antigen specific memory T cells (Tm) have shown to be an important factor in
      protecting hosts against subsequent infection by previously encountered
      pathogens. During T-cell activation, several cytokines including IL-6, IL-7 and
      IL-15, play crucial roles in the development of T cells into memory T cells. With
      the aim of generating specific Tm, we examined a strategy of sequential
      administration of molecular adjuvants. In this strategy a DNA vaccine encoding
      the VP1 capsid protein of foot and mouth disease virus (designated pcD-VP1) was
      co-delivered to mice along with an IL-6 expressing plasmid (pVAX-IL-6) as an
      initial molecular adjuvant and boosted with either an IL-7 or IL-15 expressing
      plasmid, (pVAX-IL-7 or proVAX-IL-15) as the secondary adjuvant. During the pcD
      VP1 immunization, we demonstrated that the groups primed with IL-6 and boosted
      with either IL-7 or IL-15 resulted in the enhancement of cellular and humoral
      immune responses, maturation of dendritic cells (DCs) and macrophages, and a
      higher frequency of CD4 (+) Tm (characterized by expressing CD44 (high) CD62L
      (low) markers, compared with the other groups). Thus, we took advantage of the
      different effects of cytokines on T cell development, not only to induce a higher
      level of immune responses after vaccination, but also to generate a higher ratio
      of CD4 (+) Tm in this sequential cytokine prime-boost study. This would then lead
      to the mounting of an effective long-term antigen specific immune response.

PMID- 23151451
TI  - Clinical trial in healthy malaria-naive adults to evaluate the safety,
      tolerability, immunogenicity and efficacy of MuStDO5, a five-gene,
      sporozoite/hepatic stage Plasmodium falciparum DNA vaccine combined with
      escalating dose human GM-CSF DNA.
AB  - When introduced in the 1990s, immunization with DNA plasmids was considered
      potentially revolutionary for vaccine development, particularly for vaccines
      intended to induce protective CD8 T cell responses against multiple antigens. We
      conducted, in 1997-1998, the first clinical trial in healthy humans of a DNA
      vaccine, a single plasmid encoding Plasmodium falciparum circumsporozoite protein
      (PfCSP), as an initial step toward developing a multi-antigen malaria vaccine
      targeting the liver stages of the parasite. As the next step, we conducted in
      2000-2001 a clinical trial of a five-plasmid mixture called MuStDO5 encoding pre
      erythrocytic antigens PfCSP, PfSSP2/TRAP, PfEXP1, PfLSA1 and PfLSA3. Thirty-two,
      malaria-naive, adult volunteers were enrolled sequentially into four cohorts
      receiving a mixture of 500 MUg of each plasmid plus escalating doses (0, 20, 100
      or 500 MUg) of a sixth plasmid encoding human granulocyte macrophage-colony
      stimulating factor (hGM-CSF). Three doses of each formulation were administered
      intramuscularly by needle-less jet injection at 0, 4 and 8 weeks, and each cohort
      had controlled human malaria infection administered by five mosquito bites 18 d
      later. The vaccine was safe and well-tolerated, inducing moderate antigen
      specific, MHC-restricted T cell interferon-gamma responses but no antibodies.
      Although no volunteers were protected, T cell responses were boosted post malaria
      challenge. This trial demonstrated the MuStDO5 DNA and hGM-CSF plasmids to be
      safe and modestly immunogenic for T cell responses. It also laid the foundation
      for priming with DNA plasmids and boosting with recombinant viruses, an approach
      known for nearly 15 y to enhance the immunogenicity and protective efficacy of
      DNA vaccines.

PMID- 23151453
TI  - IL-4 and IFN-gamma induced by human immunodeficiency virus vaccine in a
      schistosome infection model.
AB  - The co-infection of HIV and helminth parasites, such as Schistosoma spp, has
      increased in sub-Saharan Africa. Many HIV vaccine candidate studies have been
      completed or are in ongoing clinical trials, but it is not clear how HIV vaccines
      might affect the course of schistosome infections. In this study, we immunized S.
      mansoni-infected mice with an efficient DNA vaccine that included HIV gag. Using
      this model, we found that Th2 cytokines, such as IL-4 and IL-13, were highly
      induced after schistosome infection. Treatment of infected mice with the HIV DNA
      vaccine resulted in a significant attenuation of this rise in IL-13 expression
      and an increase in expression of the Th1 cytokine, TNF-alpha. However, vaccine
      administration did not significantly influence the expression of IL-4, or IFN
      gamma, and did not affect T cell proliferative capacity. Interestingly, the IL-4
      (+) IFN-gamma (+) phenotype appears in schistosome-infected mice that received
      HIV vaccination, and is associated with the expression of transcription factors
      GATA3 (+) T-bet (+) in these mice. These studies indicate that DNA vaccination
      can have an impact on ongoing chronic infection.

PMID- 23151454
TI  - Generation of antigen-specific immunity following systemic immunization with DNA
      vaccine encoding CCL25 chemokine immunoadjuvant.
AB  - A significant hurdle in vaccine development for many infectious pathogens is the
      ability to generate appropriate immune responses at the portal of entry, namely
      mucosal sites. The development of vaccine approaches resulting in secretory IgA
      and mucosal cellular immune responses against target pathogens is of great
      interest and in general, requires live viral infection at mucosal sites. Using
      HIV-1 and influenza A antigens as models, we report here that a novel
      systemically administered DNA vaccination strategy utilizing co-delivery of the
      specific chemokine molecular adjuvant CCL25 (TECK) can produce antigen-specific
      immune responses at distal sites including the lung and mesenteric lymph nodes in
      mice. The targeted vaccines induced infiltration of cognate chemokine receptor,
      CCR9+/CD11c+ immune cells to the site of immunization. Furthermore, data shows
      enhanced IFN-lambda secretion by antigen-specific CD3+/CD8+ and CD3+/CD4+ T
      cells, as well as elevated HIV-1-specific IgG and IgA responses in secondary
      lymphoid organs, peripheral blood, and importantly, at mucosal sites. These
      studies have significance for the development of vaccines and therapeutic
      strategies requiring mucosal immune responses and represent the first report of
      the use of plasmid co-delivery of CCL25 as part of the DNA vaccine strategy to
      boost systemic and mucosal immune responses following intramuscular injection.

PMID- 23151455
TI  - Dietary downregulation of mutant p53 levels via glucose restriction: mechanisms
      and implications for tumor therapy.
AB  - The majority of human tumors express mutant forms of p53 at high levels,
      promoting gain of oncogenic functions and correlating with disease progression,
      resistance to therapy and unfavorable prognosis. p53 mutant accumulation in
      tumors is attributed to the ability to evade degradation by the proteasome, the
      only currently recognized machinery for p53 disruption. We report here that
      glucose restriction (GR) induces p53 mutant deacetylation, routing it for
      degradation via autophagy. Depletion of p53 leads, in turn, to robust autophagic
      activation and to cell death, while expression of degradation-defective mutant
      p53 blocks autophagy and enables survival to GR. Furthermore, we found that a
      carbohydrate-free dietetic regimen that lowers the fasting glucose levels blunts
      p53 mutant expression and oncogenic activity relative to a normal diet in several
      animal model systems. These findings indicate that the stability of mutant forms
      of p53 is influenced by the levels of glucose and by dietetic habits. They also
      unravel the existence of an inhibitory loop between autophagy and mutant p53 that
      can be exploited therapeutically.

PMID- 23151456
TI  - Local gene delivery of heme oxygenase-1 by adeno-associated virus into
      osteoarthritic mouse joints exhibiting synovial oxidative stress.
AB  - OBJECTIVE: To evaluate the role of synovial oxidative stress on joint pathology
      in a spontaneous mouse model of osteoarthritis (OA) by intra-articular (IA)
      delivery of recombinant adeno-associated virus (rAAV) expressing anti-oxidant
      protein heme oxygenase-1 (HO-1). METHODS: Joint transduction by rAAV vectors was
      evaluated with serotype 1, 2, 5 and 8 capsids carrying LacZ gene administered by
      IA injections into STR/ort mice. Transduced cell types were identified by beta
      galactosidase staining in sectioned joints. Effect of oxidative stress on AAV
      transduction of primary synoviocytes in vitro was quantitated by fluorescence
      activated cell sorting (FACS) analysis. In vivo, the efficacy of rAAV1/HO-1 was
      tested by IA administration into STR/ort mice followed by histopathological
      scoring of cartilage. Levels of 3-nitrotyrosine (3-NT) and HO-1 were assessed by
      immunohistochemistry (IHC) of joint sections. RESULTS: Administration of a rAAV1
      based vector into OA mouse joints resulted in transduction of the synovium, joint
      capsule, adipocytes and skeletal muscle while none of the serotypes showed
      significant cartilage transduction. All OA joints exhibited significantly
      elevated levels of oxidative stress marker, 3-NT, in the synovium compared to OA
      resistant CBA-strain of mice. In vitro studies demonstrated that AAV transgene
      expression in primary synoviocytes was augmented by oxidative stress induced by
      H(2)O(2) and that a rAAV expressing HO-1 reduced the levels of oxidative stress.
      In vivo, HO-1 was increased in the synovium of STR/ort mice. However, delivery of
      rAAV1/HO-1 into OA joints did not reduce cartilage degradation. CONCLUSIONS: AAV
      mediated HO-1 delivery into OA joints during active disease was not sufficient to
      improve cartilage pathology in this model.

PMID- 23151457
TI  - Perturbations in the HDL metabolic pathway predispose to the development of
      osteoarthritis in mice following long-term exposure to western-type diet.
AB  - OBJECTIVE: Recent data suggest that obesity and related metabolic aberrations are
      associated with osteoarthritis (OA) development, a phenomenon that is attributed
      at least in part to the consumption of lipid-rich diets. To date, the molecular
      mechanisms that govern the lipid-OA connection remain largely unknown. Given the
      important role of high-density lipoprotein (HDL) in plasma and tissue lipid
      metabolism, the main purpose of the present study was to investigate the role of
      HDL metabolism in the pathobiology of OA. METHODS: We used apolipoprotein A-I
      (apoA-I)(-/-) mice that lack classical apoA-I containing HDL, LCAT(-/-) mice that
      have only immature HDL and relatively reduced HDL-cholesterol levels and control
      C57BL/6 mice. Mice were placed on chow or western-type (WTD) and monitored for 24
      weeks. Knee joints were removed and articular cartilage was isolated for further
      analyses. RESULTS: The LCAT(-/-) mice were significantly more sensitive to the
      development of diet-induced obesity compared to the C57BL/6 and apoA-I(-/-) mice.
      Morphological, biochemical and molecular analyses revealed that the LCAT(-/-)
      obese mice developed OA, while the C57BL/6 mice that were fed WTD did not.
      Notably, apoA-I(-/-) mice that received WTD also developed OA although their body
      weight gain was similar to their wild-type counterparts. Interestingly, bone
      marrow from LCAT(-/-) and apoA-I(-/-) mice contained significantly increased
      number of adipocytes, compared to the other groups. CONCLUSIONS: Our findings
      suggest that perturbations in HDL metabolism predispose to OA following chronic
      insult with WTD and raise the challenging possibility that HDL has a causative
      relation to OA in patients with metabolic syndrome.

PMID- 23151458
TI  - Regulation of mesenchymal stem cell chondrogenesis by glucose through protein
      kinase C/transforming growth factor signaling.
AB  - OBJECTIVE: Effective induction of human mesenchymal stem cell (hMSC)
      differentiation for regenerative medicine applications remains a great challenge.
      While much research has studied hMSC activity during differentiation, it is
      unclear whether pre-differentiation culture can modulate differentiation
      capacity. We investigate the effect of glucose concentration in pre
      differentiation/expansion culture on modulating chondrogenic capacity of hMSCs,
      and explore the underlying molecular mechanism. DESIGN: The extent of
      chondrogenesis of hMSCs previously cultured with different concentrations of
      glucose was evaluated. Transforming growth factor-beta (TGF-beta) signaling
      molecules and protein kinase C (PKC) were analyzed to identify the role of these
      molecules in the regulation of glucose on chondrogenesis. In addition, hMSCs in
      high-glucose expansion culture were treated with the PKC inhibitor to modulate
      the activity of PKC and TGF-beta signaling molecules. RESULTS: High-glucose
      maintained hMSCs were less chondrogenic than low-glucose maintained cells upon
      receiving differentiation signals. Interestingly, we found that high-glucose
      culture increased the phosphorylation of PKC and expression of type II TGF-beta
      receptor (TGFbetaRII) in pre-differentiation hMSCs. However, low-glucose
      maintained hMSCs became more responsive to chondrogenic induction with increased
      PKC activation and TGFbetaRII expression than high-glucose maintained hMSCs
      during differentiation. Inhibiting the PKC activity of high-glucose maintained
      hMSCs during expansion culture upregulated the TGFbetaRII expression of
      chondrogenic cell pellets, and enhanced chondrogenesis. CONCLUSION: Our findings
      demonstrate the effect of glucose concentration on regulating the chondrogenic
      capability of pre-differentiation hMSCs, and provide insight into the mechanism
      of how glucose concentration regulates PKC and TGF-beta signaling molecules to
      prime pre-differentiation hMSCs for subsequent chondrogenesis.

PMID- 23151459
TI  - Learning, awareness, and instruction: subjective contingency awareness does
      matter in the colour-word contingency learning paradigm.
AB  - In three experiments, each of a set colour-unrelated distracting words was
      presented most often in a particular target print colour (e.g., "month" most
      often in red). In Experiment 1, half of the participants were told the word
      colour contingencies in advance (instructed) and half were not (control). The
      instructed group showed a larger learning effect. This instruction effect was
      fully explained by increases in subjective awareness with instruction. In
      Experiment 2, contingency instructions were again given, but no contingencies
      were actually present. Although many participants claimed to be aware of these
      (non-existent) contingencies, they did not produce an instructed contingency
      effect. In Experiment 3, half of the participants were given contingency
      instructions that did not correspond to the correct contingencies. Participants
      with these false instructions learned the actual contingencies worse than
      controls. Collectively, our results suggest that conscious contingency knowledge
      might play a moderating role in the strength of implicit learning.

PMID- 23151461
TI  - A wireless body measurement system to study fatigue in multiple sclerosis.
AB  - Fatigue is reported as the most common symptom by patients with multiple
      sclerosis (MS). The physiological and functional parameters related to fatigue in
      MS patients are currently not well established. A new wearable wireless body
      measurement system, named Fatigue Monitoring System (FAMOS), was developed to
      study fatigue in MS. It can continuously measure electrocardiogram, body-skin
      temperature, electromyogram and motions of feet. The goal of this study is to
      test the ability of distinguishing fatigued MS patients from healthy subjects by
      the use of FAMOS. This paper presents the realization of the measurement system
      including the design of both hardware and dedicated signal processing algorithms.
      Twenty-six participants including 17 MS patients with fatigue and 9 sex- and age
      matched healthy controls were included in the study for continuous 24 h
      monitoring. The preliminary results show significant differences between fatigued
      MS patients and healthy controls. In conclusion, the FAMOS enables continuous
      data acquisition and estimation of multiple physiological and functional
      parameters. It provides a new, flexible and objective approach to study fatigue
      in MS, which can distinguish between fatigued MS patients and healthy controls.
      The usability and reliability of the FAMOS should however be further improved and
      validated through larger clinical trials.

PMID- 23151460
TI  - Interindividual variability and co-regulation of DNA methylation differ among
      blood cell populations.
AB  - DNA methylation regulates gene expression in a cell-type specific way. Although
      peripheral blood mononuclear cells (PBMCs) comprise a heterogeneous cell
      population, most studies of DNA methylation in blood are performed on total
      mononuclear cells. In this study, we investigated high resolution methylation
      profiles of 58 CpG sites dispersed over eight immune response genes in multiple
      purified blood cells from healthy adults and newborns. Adjacent CpG sites showed
      methylation levels that were increasingly correlated in adult blood vs. cord
      blood. Thus, while interindividual variability increases from newborn to adult
      blood, the underlying methylation changes may not be merely stochastic, but seem
      to be orchestrated as clusters of adjacent CpG sites. Multiple linear regression
      analysis showed that interindividual methylation variability was influenced by
      distance of average methylation levels to the closest border (0 or 100%),
      presence of transcription factor binding sites, CpG conservation across species
      and age. Furthermore, CD4+ and CD14+ cell types were negative predictors of
      methylation variability. Concerns that PBMC methylation differences may be
      confounded by variations in blood cell composition were justified for CpG sites
      with large methylation differences across cell types, such as in the IFN-gamma
      gene promoter. Taken together, our data suggest that unsorted mononuclear cells
      are reasonable surrogates of CD8+ and, to a lesser extent, CD4+ T cell
      methylation in adult peripheral, but not in neonatal, cord blood.

PMID- 23151462
TI  - Endogenous hydrogen sulfide formation mediates the liver damage in endotoxemic
      rats.
AB  - BACKGROUND: Hydrogen sulfide (H2S) is a naturally occurring gaseous transmitter
      and may play important roles in normal physiology and liver disease. AIMS: To
      investigate the relationships between the formation of liver H2S and liver damage
      in endotoxemic rats caused by lipopolysaccharide (LPS). METHODS: Male SD rats
      were sacrificed to acute endotoxemia and pretreated with H2S donor sodium
      hydrogen sulfide (NaHS) or H2S inhibitor dl-propargylglycine (PAG). Liver H2S
      concentration, liver cystathionine-gamma-lyase (CSE) mRNA, alanine
      aminotransferase (ALT) and aspartate aminotransferase (AST) level, liver
      histopathological alteration in different time after treatment were determined.
      RESULTS: Endotoxemia resulted in an increase in serum levels of ALT and AST. In
      the liver, endotoxemia induced a significant increase in the H2S concentration,
      and in the expression of the H2S-synthesizing enzymes CSE. Pretreatment with NaHS
      promoted the increase the liver H2S concentration and aggravated the LPS-induced
      liver damage, However, administration of PAG abolished the increase the liver H2S
      concentration and reduced the liver injury caused by endotoxemia. CONCLUSIONS:
      These findings support the view that an enhanced formation of H2S contributes to
      the liver injury in endotoxemia. We propose that inhibition of H2S synthesis may
      be a useful therapeutic strategy against the liver injury associated with
      endotoxemia.

PMID- 23151463
TI  - Quantitative assessment of bronchiolar smooth muscle in healthy and diseased
      porcine lungs.
AB  - Smooth muscle cells are major components of bronchiolar wall. Bronchiolar smooth
      muscle is reported to increase in some veterinary pulmonary disorders, but such
      assumption is not supported by detailed morphometric analyses. The present
      investigation aimed at quantitatively evaluating bronchiolar smooth muscle in
      healthy and diseased pig lungs. Our results suggest that bronchiolar smooth
      muscle cells significantly modify in size and number under different disease
      conditions, namely parasitic bronchopneumonia and Mycoplasma hyopneumoniae
      induced enzootic pneumonia. Further studies are needed in order to understand the
      pathogenesis and the functional impact of such changes.

PMID- 23151464
TI  - Free radical scavenging properties of pyrimidine derivatives.
AB  - Free radicals are well known for playing a dual role in our body- deleterious as
      well as beneficial. It includes a metabolic pathway for its generation. Oxidative
      stress in our body occurs due to excessive generation of free radicals and
      reduced level of antioxidants, but at low concentrations, these radicals help to
      perform normal physiological functions of the body. Scientific evidence suggests
      that antioxidants reduce the risk for chronic diseases including cancer and heart
      disease. This review shows current tendency in the pyrimidine synthesis and
      reveals the pyrimidine core to be a very potent moiety which can be a rich source
      for the synthesis of new compounds having desirable antioxidant activity.

PMID- 23151466
TI  - A role for pharmacotherapy in the treatment of "internet addiction".
AB  - The advent of the Internet is among the most significant changes in recent
      decades and has greatly affected the entire range of human experience. However,
      it has, in turn, led to the emergence of psychopathological features of addiction
      linked to its use. Literature on the clinical management of the distress related
      to Internet use systematically measures up to an evolving nosography, with
      ambiguous definitions of the phenomenon and a diversity of diagnostic,
      prognostic, and therapeutic criteria. To date, case studies on "Internet
      addiction" treatment are rather limited, and no standard clinical treatment
      protocols exist. With regard to pharmacological treatment options, empirical or
      anecdotal assessments are mostly referred to. The aim of this article was to
      review current literature on Internet addiction treatment and assess the extent
      to which specific pharmacological interventions alleviate these patients'
      symptomatic burden, to propose a rationale that may guide the therapeutic
      approach. To this end, we also explored pharmacological interventions that target
      patterns of comorbidity and underlying psychopathological dimensions shared with
      other behavioral or substance addictions.

PMID- 23151467
TI  - Nocturnal eating/drinking syndrome with restless legs syndrome caused by
      neuroleptics improved by Yi-Gan San add-on treatment: a case report.
AB  - Nocturnal eating/drinking syndrome is characterized by awakening in the middle
      of the night, getting out of bed, and consuming large quantities of food quickly
      and uncontrollably. We report a middle-aged male patient with schizophrenia who
      had nocturnal eating/drinking syndrome with restless legs syndrome whose
      condition improved with the administration of the herbal medicine Yi-Gan San
      (Yokukan-San in Japanese).

PMID- 23151468
TI  - Orofacial dyskinesia after moxifloxacin treatment--a case with normal hepatorenal
      function and review of literature.
AB  - BACKGROUND: Orofacial dyskinesia is rarely reported with antibiotics. Among
      antibiotics, third-generation fluoroquinolones are known to cause movement
      disorders. We report the first patient who developed orofacial dyskinesia after
      taking a fourth-generation fluoroquinolone, namely, moxifloxacin. METHODS: The
      patient is a 58-year-old woman who was treated with moxifloxacin for acute
      bronchitis. She developed orofacial dyskinesia involving the tongue, lips, and
      facial muscles after treatment. RESULTS: Discontinuation of moxifloxacin and
      treatment with clonidine resulted in significant reduction of orofacial
      dyskinesia over the period of 8 to 12 weeks. A review of literature shows reports
      of a variety of involuntary movements with third-generation fluoroquinolones,
      mostly manifesting in patients with impaired renal and kidney function.
      CONCLUSIONS: The fourth-generation fluoroquinolone moxifloxacin can cause
      orofacial dyskinesia like third-generation fluoroquinolone antibiotics and in a
      patient with normal renal and liver function.

PMID- 23151465
TI  - Rapalogs in cancer prevention: anti-aging or anticancer?
AB  - Common cancer is an age-related disease. Slow aging is associated with reduced
      and delayed carcinogenesis. Calorie restriction (CR), the most studied anti-aging
      intervention, prevents cancer by slowing down the aging process. Evidence is
      emerging that CR decelerates aging by deactivating MTOR (Target of Rapamycin).
      Rapamycin and other rapalogs suppress cellular senescence, slow down aging and
      postpone age-related diseases including cancer. At the same time, rapalogs are
      approved for certain cancer treatments. Can cancer prevention be explained by
      direct targeting of cancer cells? Or does rapamycin prevent cancer indirectly
      through slowing down the aging process? Increasing evidence points to the latter
      scenario.

PMID- 23151469
TI  - Eslicarbazepine acetate in the management of refractory bipolar disorder.
AB  - Eslicarbazepine acetate is a novel third-generation antiepileptic related to
      carbamazepine and oxcarbazepine with a benign adverse effect profile. We report a
      patient with bipolar mania with intolerance to multiple antimanic drugs,
      responding to eslicarbazepine without any serious adverse effect.

PMID- 23151470
TI  - Pantothenate's possible role in schizophrenia pathogenesis.

PMID- 23151471
TI  - Antipsychotics and abnormal liver function tests.

PMID- 23151472
TI  - Juvenile myoclonic epilepsy: the impact of clinical variables and psychiatric
      disorders on executive profile assessed with a comprehensive neuropsychological
      battery.
AB  - Executive dysfunction is reported in juvenile myoclonic epilepsy (JME). However,
      batteries employed in previous studies included no more than three tests of
      executive function. In this study, we aimed to assess executive and attentional
      functions in JME using a comprehensive battery of eight tests (encompassing
      fifteen subtests). We also evaluated neuropsychological profiles using a clinical
      criterion of severity and correlated these findings with epilepsy clinical
      variables and the presence of psychiatric disorders. We prospectively evaluated
      42 patients with JME and a matched control group with Digit Span tests (forward
      and backward), Stroop Color-Word Test, Trail Making Test, Wisconsin Card-Sorting
      Test, Matching Familiar Figures Test and Word Fluency Test. We estimated IQ with
      the Matrix Reasoning and Vocabulary subtests of the Wechsler Abbreviated
      Intelligence Scale. The patients with JME showed specific deficits in working
      memory, inhibitory control, concept formation, goal maintenance, mental
      flexibility, and verbal fluency. We observed attentional deficits in processes
      such as alertness and attention span and those requiring sustained and divided
      attention. We found that 83.33% of the patients had moderate or severe executive
      dysfunction. In addition, attentional and executive impairment was correlated
      with higher frequency of seizures and the presence of psychiatric disorders.
      Furthermore, executive dysfunction correlated with a longer duration of epilepsy.
      Our findings indicate the need for comprehensive neuropsychological batteries in
      patients with JME, in order to provide a more extensive evaluation of attentional
      and executive functions and to show that some relevant deficits have been
      overlooked.

PMID- 23151473
TI  - Virtual screening and QSAR study of some pyrrolidine derivatives as alpha
      mannosidase inhibitors for binding feature analysis.
AB  - Virtual screening and QSAR analysis were carried out to investigate the binding
      features of (2R, 3R, 4S)-2-aminomethylpyrrolidine 3,4-diol and the functionalized
      pyrrolidine derivatives to the alpha-mannosidase I and II enzymes. The QSAR
      models (possessed considerable R(2), Q(2) values, etc.) suggested that the
      presence of polar property on the vdW surface (vsurf_W, vsurf_Wp, etc.) of the
      molecules is important along with the presence of aromatic rings (opr_violation)
      in the molecules (which also provide hydrophobicity to the molecules). The
      docking study performed on alpha-mannosidase I and II enzymes pointed that the
      main interactions occur by hydrogen bonds, hydrophobic pi-pi stacking contacts
      and salt bridges with the cation calcium (for alpha-mannosidase I) and close
      interaction with zinc ion (alpha-mannosidase II), respectively. The bond
      flexibility orientates the aromatic ring in the molecules toward the hydrophobic
      cavity for pi-pi stacking contacts with the aromatic amino acids (Phe528, Phe329
      and Phe659 for alpha-mannosidase I and Trp95, Tyr269, Phe312, Tyr102 for alpha
      mannosidase II). The pharmacophore analysis also supports the results derived
      from the docking and QSAR studies. Our results suggest that the best compound to
      inhibit both classes of alpha-mannosidase is the compound 30, which may be used
      to design similar and better inhibitors to next generation drugs.

PMID- 23151474
TI  - Circadian rhythms: Depression brought to light.

PMID- 23151475
TI  - RNAi triggered by specialized machinery silences developmental genes and
      retrotransposons.
AB  - RNA interference (RNAi) is a conserved mechanism in which small interfering RNAs
      (siRNAs) guide the degradation of cognate RNAs, but also promote heterochromatin
      assembly at repetitive DNA elements such as centromeric repeats. However, the
      full extent of RNAi functions and its endogenous targets have not been explored.
      Here we show that, in the fission yeast Schizosaccharomyces pombe, RNAi and
      heterochromatin factors cooperate to silence diverse loci, including sexual
      differentiation genes, genes encoding transmembrane proteins, and
      retrotransposons that are also targeted by the exosome RNA degradation machinery.
      In the absence of the exosome, transcripts are processed preferentially by the
      RNAi machinery, revealing siRNA clusters and a corresponding increase in
      heterochromatin modifications across large domains containing genes and
      retrotransposons. We show that the generation of siRNAs and heterochromatin
      assembly by RNAi is triggered by a mechanism involving the canonical poly(A)
      polymerase Pla1 and an associated RNA surveillance factor Red1, which also
      activate the exosome. Notably, siRNA production and heterochromatin modifications
      at these target loci are regulated by environmental growth conditions, and by
      developmental signals that induce gene expression during sexual differentiation.
      Our analyses uncover an interaction between RNAi and the exosome that is
      conserved in Drosophila, and show that differentiation signals modulate RNAi
      silencing to regulate developmental genes.

PMID- 23151477
TI  - Low-temperature physics: a chilling effect for molecules.

PMID- 23151476
TI  - Aberrant light directly impairs mood and learning through melanopsin-expressing
      neurons.
AB  - The daily solar cycle allows organisms to synchronize their circadian rhythms and
      sleep-wake cycles to the correct temporal niche. Changes in day-length, shift
      work, and transmeridian travel lead to mood alterations and cognitive function
      deficits. Sleep deprivation and circadian disruption underlie mood and cognitive
      disorders associated with irregular light schedules. Whether irregular light
      schedules directly affect mood and cognitive functions in the context of normal
      sleep and circadian rhythms remains unclear. Here we show, using an aberrant
      light cycle that neither changes the amount and architecture of sleep nor causes
      changes in the circadian timing system, that light directly regulates mood
      related behaviours and cognitive functions in mice. Animals exposed to the
      aberrant light cycle maintain daily corticosterone rhythms, but the overall
      levels of corticosterone are increased. Despite normal circadian and sleep
      structures, these animals show increased depression-like behaviours and impaired
      hippocampal long-term potentiation and learning. Administration of the
      antidepressant drugs fluoxetine or desipramine restores learning in mice exposed
      to the aberrant light cycle, suggesting that the mood deficit precedes the
      learning impairments. To determine the retinal circuits underlying this
      impairment of mood and learning, we examined the behavioural consequences of this
      light cycle in animals that lack intrinsically photosensitive retinal ganglion
      cells. In these animals, the aberrant light cycle does not impair mood and
      learning, despite the presence of the conventional retinal ganglion cells and the
      ability of these animals to detect light for image formation. These findings
      demonstrate the ability of light to influence cognitive and mood functions
      directly through intrinsically photosensitive retinal ganglion cells.

PMID- 23151478
TI  - Rapid coupling between ice volume and polar temperature over the past 150,000
      years.
AB  - Current global warming necessitates a detailed understanding of the relationships
      between climate and global ice volume. Highly resolved and continuous sea-level
      records are essential for quantifying ice-volume changes. However, an unbiased
      study of the timing of past ice-volume changes, relative to polar climate change,
      has so far been impossible because available sea-level records either were dated
      by using orbital tuning or ice-core timescales, or were discontinuous in time.
      Here we present an independent dating of a continuous, high-resolution sea-level
      record in millennial-scale detail throughout the past 150,000 years. We find that
      the timing of ice-volume fluctuations agrees well with that of variations in
      Antarctic climate and especially Greenland climate. Amplitudes of ice-volume
      fluctuations more closely match Antarctic (rather than Greenland) climate
      changes. Polar climate and ice-volume changes, and their rates of change, are
      found to covary within centennial response times. Finally, rates of sea-level
      rise reached at least 1.2 m per century during all major episodes of ice-volume
      reduction.

PMID- 23151479
TI  - Tet1 controls meiosis by regulating meiotic gene expression.
AB  - Meiosis is a germ-cell-specific cell division process through which haploid
      gametes are produced for sexual reproduction. Before the initiation of meiosis,
      mouse primordial germ cells undergo a series of epigenetic reprogramming steps,
      including the global erasure of DNA methylation at the 5-position of cytosine
      (5mC) in CpG-rich DNA. Although several epigenetic regulators, such as Dnmt3l and
      the histone methyltransferases G9a and Prdm9, have been reported to be crucial
      for meiosis, little is known about how the expression of meiotic genes is
      regulated and how their expression contributes to normal meiosis. Using a loss-of
      function approach in mice, here we show that the 5mC-specific dioxygenase Tet1
      has an important role in regulating meiosis in mouse oocytes. Tet1 deficiency
      significantly reduces female germ-cell numbers and fertility. Univalent
      chromosomes and unresolved DNA double-strand breaks are also observed in Tet1
      deficient oocytes. Tet1 deficiency does not greatly affect the genome-wide
      demethylation that takes place in primordial germ cells, but leads to defective
      DNA demethylation and decreased expression of a subset of meiotic genes. Our
      study thus establishes a function for Tet1 in meiosis and meiotic gene activation
      in female germ cells.

PMID- 23151480
TI  - Sisyphus cooling of electrically trapped polyatomic molecules.
AB  - Polar molecules have a rich internal structure and long-range dipole-dipole
      interactions, making them useful for quantum-controlled applications and
      fundamental investigations. Their potential fully unfolds at ultracold
      temperatures, where various effects are predicted in many-body physics, quantum
      information science, ultracold chemistry and physics beyond the standard model.
      Whereas a wide range of methods to produce cold molecular ensembles have been
      developed, the cooling of polyatomic molecules (that is, with three or more
      atoms) to ultracold temperatures has seemed intractable. Here we report the
      experimental realization of optoelectrical cooling, a recently proposed cooling
      and accumulation method for polar molecules. Its key attribute is the removal of
      a large fraction of a molecule's kinetic energy in each cycle of the cooling
      sequence via a Sisyphus effect, allowing cooling with only a few repetitions of
      the dissipative decay process. We demonstrate the potential of optoelectrical
      cooling by reducing the temperature of about one million CH(3)F molecules by a
      factor of 13.5, with the phase-space density increased by a factor of 29 (or a
      factor of 70 discounting trap losses). In contrast to other cooling mechanisms,
      our scheme proceeds in a trap, cools in all three dimensions and should work for
      a large variety of polar molecules. With no fundamental temperature limit
      anticipated down to the photon-recoil temperature in the nanokelvin range, we
      expect our method to be able to produce ultracold polyatomic molecules. The low
      temperatures, large molecule numbers and long trapping times of up to 27 seconds
      should allow an interaction-dominated regime to be attained, enabling collision
      studies and investigation of evaporative cooling towards a Bose-Einstein
      condensate of polyatomic molecules.

PMID- 23151482
TI  - Structure and function of the initially transcribing RNA polymerase II-TFIIB
      complex.
AB  - The general transcription factor (TF) IIB is required for RNA polymerase (Pol) II
      initiation and extends with its B-reader element into the Pol II active centre
      cleft. Low-resolution structures of the Pol II-TFIIB complex indicated how TFIIB
      functions in DNA recruitment, but they lacked nucleic acids and half of the B
      reader, leaving other TFIIB functions enigmatic. Here we report crystal
      structures of the Pol II-TFIIB complex from the yeast Saccharomyces cerevisiae at
      3.4 A resolution and of an initially transcribing complex that additionally
      contains the DNA template and a 6-nucleotide RNA product. The structures reveal
      the entire B-reader and protein-nucleic acid interactions, and together with
      functional data lead to a more complete understanding of transcription
      initiation. TFIIB partially closes the polymerase cleft to position DNA and
      assist in its opening. The B-reader does not reach the active site but binds the
      DNA template strand upstream to assist in the recognition of the initiator
      sequence and in positioning the transcription start site. TFIIB rearranges active
      site residues, induces binding of the catalytic metal ion B, and stimulates
      initial RNA synthesis allosterically. TFIIB then prevents the emerging DNA-RNA
      hybrid duplex from tilting, which would impair RNA synthesis. When the RNA grows
      beyond 6 nucleotides, it is separated from DNA and is directed to its exit tunnel
      by the B-reader loop. Once the RNA grows to 12-13 nucleotides, it clashes with
      TFIIB, triggering TFIIB displacement and elongation complex formation. Similar
      mechanisms may underlie all cellular transcription because all eukaryotic and
      archaeal RNA polymerases use TFIIB-like factors, and the bacterial initiation
      factor sigma has TFIIB-like topology and contains the loop region 3.2 that
      resembles the B-reader loop in location, charge and function. TFIIB and its
      counterparts may thus account for the two fundamental properties that distinguish
      RNA from DNA polymerases: primer-independent chain initiation and product
      separation from the template.

PMID- 23151484
TI  - Craving: a research update: editorial to a special issue.

PMID- 23151485
TI  - Association of ANXA11 genetic variation with sarcoidosis in African Americans and
      European Americans.
AB  - A recent genome-wide association study in a German population and two subsequent
      studies in European populations found that a non-synonymous single-nucleotide
      polymorphism (SNP), rs1049550, within the annexin A11 (ANXA11) gene was
      associated with susceptibility to sarcoidosis. We sought to identify additional
      ANXA11 variants independently associated with sarcoidosis, determine whether any
      sarcoidosis-associated ANXA11 variants were associated with chest radiographic
      phenotypes, and explore human leukocyte antigen (HLA) SNP-SNP interactions with
      ANXA11. A total of 209 SNPs spanning 100 kb including the 5' promoter, coding,
      and 3' untranslated regions of ANXA11 were genotyped for 1689 sarcoidosis cases
      and 1252 controls. After adjustment for rs1049550, two additional novel ANXA11
      sarcoidosis associations were identified only in African Americans--rs61860052
      (odds ratio (OR)=0.62; 95% confidence interval (CI)=0.40-0.97) and rs4377299
      (OR=1.31; 95% CI=1.06-1.63). These associations were more pronounced in
      radiologically-classified Scadding stage IV sarcoidosis cases. We also identified
      a significant SNP-SNP interaction between rs1049550 and a sarcoidosis risk SNP
      (rs9268839) near the HLA-DRA locus. This further genetic dissection of ANXA11 may
      provide additional insight into the immune dysregulation characteristic of
      sarcoidosis pathophysiology.

PMID- 23151486
TI  - Variation in the TLR10/TLR1/TLR6 locus is the major genetic determinant of
      interindividual difference in TLR1/2-mediated responses.
AB  - Toll-like receptor (TLR)-mediated innate immune responses are important in early
      host defense. Using a candidate gene approach, we previously identified genetic
      variation within TLR1 that is associated with hyper-responsiveness to a TLR1/2
      agonist in vitro and with death and organ dysfunction in patients with sepsis.
      Here we report a genome-wide association study (GWAS) designed to identify
      genetic loci controlling whole blood cytokine responses to the TLR1/2 lipopeptide
      agonist, Pam(3)CSK(4) (N-palmitoyl-S-dipalmitoylglyceryl Cys-Ser-(Lys)(4)) ex
      vivo. We identified a very strong association (P<1 * 10(-27)) between genetic
      variation within the TLR10/1/6 locus on chromosome 4, and Pam(3)CSK(4)-induced
      cytokine responses. This was the predominant association explaining over 35% of
      the population variance for this phenotype. Notably, strong associations were
      observed within TLR10, suggesting that genetic variation in TLR10 may influence
      bacterial lipoprotein-induced responses. These findings establish the TLR10/1/6
      locus as the dominant common genetic factor controlling interindividual
      variability in Pam(3)CSK(4)-induced whole blood responses in the healthy
      population.

PMID- 23151488
TI  - Resistance to plague of Mus spretus SEG/Pas mice requires the combined action of
      at least four genetic factors.
AB  - We have previously described SEG/Pas as the first mouse inbred strain able to
      survive subcutaneous injection of virulent Yersinia pestis, the agent of plague,
      and we identified Yprl1, Yprl2 and Yprl3 as three quantitative trait loci (QTLs)
      controlling this exceptional phenotype in females from a backcross between
      SEG/Pas and C57BL/6 strains. We have now developed congenic strains to further
      characterize the extent and effect of these genomic regions. In this study, we
      confirm the importance of two of these regions, both in males and females, while
      the third one may well be a spurious association. We show that no genomic region
      alone is able to increase the survival of C57BL/6 mice, but that C57BL/6 mice
      carrying both Yprl2 and Yprl3 exhibit intermediate resistance. Each of these two
      QTLs contains at least two subregions, which are required to increase survival.
      Finally, through the analysis of congenic strains in an F1 background, we
      establish the mode of inheritance of the SEG-derived resistance alleles.
      Altogether, this study has clarified and enhanced our understanding of the
      genetic architecture of resistance to plague in SEG/Pas mice.

PMID- 23151487
TI  - Influence of intragenic CCL3 haplotypes and CCL3L copy number in HIV-1 infection
      in a sub-Saharan African population.
AB  - Two CCL3 haplotypes (HapA1 and Hap-A3) and two polymorphic positions shared by
      the haplotypes (Hap-2SNP (single nucleotide polymorphism)) were investigated
      together with CCL3L copy number (CN), for their role in HIV-1 disease. Hap-A1 was
      associated with protection from in utero HIV-1 infection: exposed uninfected (EU)
      infants had higher representation of wild type (WT)/Hap-A1 than infected infants
      (excluding intrapartum (IP)-infected infants), which maintained significance post
      maternal Nevirapine (mNVP) and viral load (MVL) correction (P=0.04; odds ratio
      (OR)=0.33). Mother-infant pair analyses showed the protective effect of Hap-A1 is
      dependent on its presence in the infant. Hap-A3 was associated with increased IP
      transmission: WT/Hap-A3 was increased in IP-transmitting vs non-transmitting (NT)
      mothers, and remained significant post mNVP and MVL correction (P=0.02; OR=3.50).
      This deleterious effect of Hap-A3 seemed dependent on its presence in the mother.
      Hap-2SNP was associated with lower CD4 count in the NT mothers (P=0.03). CCL3 Hap
      A1 was associated with high CCL3L CN in total (P=0.001) and EU infants (P=0.006);
      the effect was not additive, however, having either Hap-A1 or high CCL3L CN was
      more significantly (P=0.0008) associated with protection from in utero infection
      than Hap-A1 (P=0.028) or high CCL3L CN (P=0.002) alone. Linkage disequilibrium
      between Hap-A1 and high CCL3L CN appears unlikely given that a Nigerian
      population showed an opposite relationship.

PMID- 23151489
TI  - Multiple sclerosis-associated single-nucleotide polymorphisms in CLEC16A
      correlate with reduced SOCS1 and DEXI expression in the thymus.
AB  - Genome-wide association studies have revealed that the 16p13 chromosomal region,
      including CLEC16A, DEXI, CIITA and SOCS1, is associated with susceptibility to
      autoimmune diseases. As non-coding single-nucleotide polymorphisms (SNPs) may
      confer susceptibility to disease by affecting expression of nearby genes, we
      examined whether autoimmune-associated intronic CLEC16A SNPs (rs12708716,
      rs6498169 and rs7206912) correlate with the expression of CLEC16A itself as well
      as neighboring genes in whole-blood and thymic samples. Real-time quantitative
      PCR analyses show that SOCS1 and DEXI expression was lower in thymic samples
      carrying at least one of the CLEC16A risk alleles compared with non-carriers of
      the risk allele. Linear regression analysis revealed a significant correlation
      between the expression level of CLEC16A and that of SOCS1 and DEXI in thymic
      samples. These data indicate a possible regulatory role for multiple sclerosis
      associated non-coding CLEC16A SNPs and a common control mechanism for the
      expression of CLEC16A, SOCS1 and DEXI.

PMID- 23151490
TI  - Solid-state STRAFI NMR probe for material imaging of quadrupolar nuclei.
AB  - Stray field imaging (STRAFI) has provided an alternative imaging method to study
      solid materials that are typically difficult to obtain using conventional MRI
      methods. For small volume samples, image resolution is a challenge since
      extremely strong gradients are required to examine narrow slices. Here we present
      a STRAFI probe for imaging materials with quadrupolar nuclei. Experiments were
      performed on a 19.6 T magnet which has a fringe field gradient strength of 72
      T/m, nearly 50 times stronger than commercial microimagers. We demonstrate the
      ability to acquire (7)Li 1D profiles of liquid and solid state lithium phantoms
      with clearly resolved features in the micrometer scale and as a practical example
      a Li ion battery electrode material is also examined.

PMID- 23151491
TI  - Planned home birth: the professional responsibility response.
AB  - This article addresses the recrudescence of and new support for midwife
      supervised planned home birth in the United States and the other developed
      countries in the context of professional responsibility. Advocates of planned
      home birth have emphasized patient safety, patient satisfaction, cost
      effectiveness, and respect for women's rights. We provide a critical evaluation
      of each of these claims and identify professionally appropriate responses of
      obstetricians and other concerned physicians to planned home birth. We start with
      patient safety and show that planned home birth has unnecessary, preventable,
      irremediable increased risk of harm for pregnant, fetal, and neonatal patients.
      We document that the persistently high rates of emergency transport undermines
      patient safety and satisfaction, the raison d'etre of planned home birth, and
      that a comprehensive analysis undermines claims about the cost-effectiveness of
      planned home birth. We then argue that obstetricians and other concerned
      physicians should understand, identify, and correct the root causes of the
      recrudescence of planned home birth; respond to expressions of interest in
      planned home birth by women with evidence-based recommendations against it;
      refuse to participate in planned home birth; but still provide excellent and
      compassionate emergency obstetric care to women transported from planned home
      birth. We explain why obstetricians should not participate in or refer to
      randomized clinical trials of planned home vs planned hospital birth. We call on
      obstetricians, other concerned physicians, midwives and other obstetric
      providers, and their professional associations not to support planned home birth
      when there are safe and compassionate hospital-based alternatives and to advocate
      for a safe home-birth-like experience in the hospital.

PMID- 23151492
TI  - Allogeneic transplantation: when is a mismatch better than a match?

PMID- 23151493
TI  - In search of immunodominant minor histocompatibility antigens.

PMID- 23151494
TI  - Quantitative falls risk estimation through multi-sensor assessment of standing
      balance.
AB  - Falls are the most common cause of injury and hospitalization and one of the
      principal causes of death and disability in older adults worldwide. Measures of
      postural stability have been associated with the incidence of falls in older
      adults. The aim of this study was to develop a model that accurately classifies
      fallers and non-fallers using novel multi-sensor quantitative balance metrics
      that can be easily deployed into a home or clinic setting. We compared the
      classification accuracy of our model with an established method for falls risk
      assessment, the Berg balance scale. Data were acquired using two sensor
      modalities--a pressure sensitive platform sensor and a body-worn inertial sensor,
      mounted on the lower back--from 120 community dwelling older adults (65 with a
      history of falls, 55 without, mean age 73.7 +/- 5.8 years, 63 female) while
      performing a number of standing balance tasks in a geriatric research clinic.
      Results obtained using a support vector machine yielded a mean classification
      accuracy of 71.52% (95% CI: 68.82-74.28) in classifying falls history, obtained
      using one model classifying all data points. Considering male and female
      participant data separately yielded classification accuracies of 72.80% (95% CI:
      68.85-77.17) and 73.33% (95% CI: 69.88-76.81) respectively, leading to a mean
      classification accuracy of 73.07% in identifying participants with a history of
      falls. Results compare favourably to those obtained using the Berg balance scale
      (mean classification accuracy: 59.42% (95% CI: 56.96-61.88)). Results from the
      present study could lead to a robust method for assessing falls risk in both
      supervised and unsupervised environments.

PMID- 23151495
TI  - Resistance to antibody neutralization in HIV-2 infection occurs in late stage
      disease and is associated with X4 tropism.
AB  - OBJECTIVES: To characterize the nature and dynamics of the neutralizing antibody
      (NAb) response and escape in chronically HIV-2 infected patients. METHODS: Twenty
      eight chronically infected adults were studied over a period of 1-4 years. The
      neutralizing activity of plasma immunoglobulin G (IgG) antibodies against
      autologous and heterologous primary isolates was analyzed using a standard assay
      in TZM-bl cells. Coreceptor usage was determined in ghost cells. The sequence and
      predicted three-dimensional structure of the C2V3C3 Env region were determined
      for all isolates. RESULTS: Only 50% of the patients consistently produced IgG
      NAbs to autologous and contemporaneous virus isolates. In contrast, 96% of the
      patients produced IgG antibodies that neutralized at least two isolates of a
      panel of six heterologous R5 isolates. Breadth and potency of the neutralizing
      antibodies were positively associated with the number of CD4(+) T cells and with
      the titer and avidity of C2V3C3-specific binding IgG antibodies. X4 isolates were
      obtained only from late stage disease patients and were fully resistant to
      neutralization. The V3 loop of X4 viruses was longer, had a higher net charge,
      and differed markedly in secondary structure compared to R5 viruses. CONCLUSION:
      Most HIV-2 patients infected with R5 isolates produce C2V3C3-specific
      neutralizing antibodies whose potency and breadth decreases as the disease
      progresses. Resistance to antibody neutralization occurs in late stage disease
      and is usually associated with X4 viral tropism and major changes in V3 sequence
      and conformation. Our studies support a model of HIV-2 pathogenesis in which the
      neutralizing antibodies play a central role and have clear implications for the
      vaccine field.

PMID- 23151496
TI  - Putting risk compensation to rest:  reframing the relationship between risk
      behavior and antiretroviral therapy among injection drug users.

PMID- 23151497
TI  - Serotonin syndrome following drug-drug interactions and CYP2D6 and CYP2C19
      genetic polymorphisms in an HIV-infected patient.

PMID- 23151498
TI  - Undiagnosed HIV prevalence in France:  no evidence against universal HIV
      screening.

PMID- 23151500
TI  - Raltegravir in the prevention of mother-to-child transmission of HIV-1: 
      effective transplacental transfer and delayed plasma clearance observed in
      preterm neonates.

PMID- 23151501
TI  - FGFR1 amplification and the progression of non-invasive to invasive breast
      cancer.
AB  - The incidence of invasive breast cancer (IBC) can be dramatically reduced by
      improving our abilities to detect and treat ductal carcinoma in situ (DCIS).
      Progress will be based on a detailed understanding of molecular mechanisms
      responsible for tumor progression. An interesting study by Jang and colleagues
      evaluated and compared the frequency of amplification of four oncogenes (HER2, c
      MYC, CCND1 and FGFR1) in large cohorts of pure DCIS, in the DCIS component of
      IBC, and in corresponding IBC. Of particular interest, they found a twofold
      increase in FGFR1 amplification in IBC versus pure DCIS, and significantly
      reduced disease-free survival in amplified versus unamplified IBC - leading the
      authors to conclude that FGFR1 plays an important role in the development and
      progression of IBC. These observations indeed provide hints that FGFR1 is
      important in this setting, although the issue is very complex and far from
      resolved. 

PMID- 23151502
TI  - Renegotiating sex and intimacy after cancer: resisting the coital imperative.
AB  - BACKGROUND: Previous research on sex and intimacy in the context of cancer has
      focused on documenting sexual changes and difficulties, primarily focusing on
      heterosexual individuals who have sexual or reproductive cancers. Analyses of
      sexual renegotiation and the social construction of sex are largely absent from
      the research agenda. OBJECTIVE: The objective of this study was to explore
      renegotiation of sex in individuals with cancer, and in partners, across a broad
      range of cancer types and relational contexts. METHODS: Semistructured interviews
      were conducted with 44 people with cancer (23 women, 21 men) and 35 partners (18
      women, 17 men), 86% of whom identified as heterosexual. The data were analyzed
      with theoretical thematic analysis, from a material-discursive-intrapsychic
      perspective. RESULTS: Renegotiation of sex or intimacy was reported by 70% of
      participants, reflected in 3 themes: "resisting the coital imperative: redefining
      'sex,'" "resisting the coital imperative: embracing intimacy," and "adopting the
      coital imperative: refiguring the body through techno-medicine." The importance
      of relational context was reflected in the theme "the inter-subjective nature of
      sexual re-negotiation: relationship context and communication." CONCLUSIONS:
      Whereas previous research has focused on embodied changes associated with
      sexuality after cancer, or their psychological consequences, the findings of the
      present study suggest that hegemonic constructions of "sex," in particular the
      coital imperative, are central to the experience and negotiation of sex and
      intimacy after cancer. IMPLICATIONS FOR PRACTICE: Resistance of the coital
      imperative should be a fundamental aspect of information and support provided by
      health professionals who seek to reduce distress associated with sexual changes
      after cancer.

PMID- 23151503
TI  - Patterns and correlates of missed nursing care in inpatient oncology units.
AB  - BACKGROUND: Missed nursing care influences the quality of hospital care, yet this
      problem has not been explored in the oncology setting, nor are the correlates of
      missed nursing care in inpatient oncology settings understood. OBJECTIVE: We
      examined the frequency of missed care in oncology units, differences in missed
      care between oncology and non-oncology units, and the relationship between unit
      staffing and missed care. METHODS: We performed secondary analysis of survey data
      collected in 2008 to 2009 across 9 hospitals. The MISSCARE Survey was
      administered to nurses and medical assistants employed in 62 units (n = 2318).
      Descriptive statistics and linear regression were used to examine the frequency
      of missed care, differences between oncology (n = 12) and non-oncology units
      (n=50), and the relationship between unit staffing and missed care. RESULTS:
      Oncology nursing unit personnel reported ambulation, care conference attendance,
      and mouth care as most frequently missed. Oncology units had significantly lower
      missed care than did non-oncology units (P < .05). Higher patient assignments
      were associated with an increase in reported missed care (P < .05). CONCLUSIONS:
      Missed care is a problem shared by inpatient oncology and non-oncology units.
      Missed ambulation and mouth care are worrisome, given their importance to
      oncology patients. Suboptimal staffing increases missed care. IMPLICATIONS FOR
      PRACTICE: These data motivate quality improvement and evidence-based management.
      Clinicians can strategize to ensure patients receive adequate ambulation and
      mouth care. Managers can use our findings to support the importance of stable
      nurse staffing to reduce untoward patient outcomes.

PMID- 23151504
TI  - Attitudes and experiences of nurses toward death and caring for dying patients in
      Turkey.
AB  - BACKGROUND: Caring of the dying patients and facing the death can be a stressful
      and difficult experience for nurses. Besides personal and professional
      experiences, nurses' own attitudes toward death may affect the care given to
      dying individuals. OBJECTIVE: The aim of this study was to examine Turkish
      nurses' attitudes toward and experiences with death and caring for dying
      patients. METHODS: A descriptive, cross-sectional study was conducted at 2
      university hospitals and 1 state hospital located in Ankara, Turkey. Data were
      collected via sociodemographics form, the Death Attitude Profile-Revised, and
      Frommelt's Attitude Toward Caring for Dying Patients. RESULTS: The attitudes of
      Turkish nurses toward death and caring for dying patients are less positive than
      the reported attitudes of nurses in other studies. Significant relationships were
      found among level of education, willingness to care for dying patients, and
      scores on Frommelt's Attitude Toward Caring for Dying Patients and on Death
      Attitude Profile-Revised subscales (P < .05). Although the majority of nurses
      (85%) stated that they had received education on end of life, most of them (82%)
      were not comfortable talking about death. CONCLUSIONS: A lack of education and
      experience may contribute to the negative attitudes. Providing a reflective
      narrative environment in which nurses can express their personal feelings about
      death and dying could be a potentially effective approach. IMPLICATIONS FOR
      PRACTICE: This study highlights the need for further educational research and
      development of better educational programs to help nurses to explore and
      understand their attitudes toward death, overcome fears, increase communication
      skills, and enhance coping strategies.

PMID- 23151506
TI  - Frequency modulation entrains slow neural oscillations and optimizes human
      listening behavior.
AB  - The human ability to continuously track dynamic environmental stimuli, in
      particular speech, is proposed to profit from "entrainment" of endogenous neural
      oscillations, which involves phase reorganization such that "optimal" phase comes
      into line with temporally expected critical events, resulting in improved
      processing. The current experiment goes beyond previous work in this domain by
      addressing two thus far unanswered questions. First, how general is neural
      entrainment to environmental rhythms: Can neural oscillations be entrained by
      temporal dynamics of ongoing rhythmic stimuli without abrupt onsets? Second, does
      neural entrainment optimize performance of the perceptual system: Does human
      auditory perception benefit from neural phase reorganization? In a human
      electroencephalography study, listeners detected short gaps distributed uniformly
      with respect to the phase angle of a 3-Hz frequency-modulated stimulus.
      Listeners' ability to detect gaps in the frequency-modulated sound was not
      uniformly distributed in time, but clustered in certain preferred phases of the
      modulation. Moreover, the optimal stimulus phase was individually determined by
      the neural delta oscillation entrained by the stimulus. Finally, delta phase
      predicted behavior better than stimulus phase or the event-related potential
      after the gap. This study demonstrates behavioral benefits of phase realignment
      in response to frequency-modulated auditory stimuli, overall suggesting that
      frequency fluctuations in natural environmental input provide a pacing signal for
      endogenous neural oscillations, thereby influencing perceptual processing.

PMID- 23151505
TI  - Merck Ad5/HIV induces broad innate immune activation that predicts CD8+ T-cell
      responses but is attenuated by preexisting Ad5 immunity.
AB  - To better understand how innate immune responses to vaccination can lead to
      lasting protective immunity, we used a systems approach to define immune
      signatures in humans over 1 wk following MRKAd5/HIV vaccination that predicted
      subsequent HIV-specific T-cell responses. Within 24 h, striking increases in
      peripheral blood mononuclear cell gene expression associated with inflammation,
      IFN response, and myeloid cell trafficking occurred, and lymphocyte-specific
      transcripts decreased. These alterations were corroborated by marked serum
      inflammatory cytokine elevations and egress of circulating lymphocytes. Responses
      of vaccinees with preexisting adenovirus serotype 5 (Ad5) neutralizing antibodies
      were strongly attenuated, suggesting that enhanced HIV acquisition in Ad5
      seropositive subgroups in the Step Study may relate to the lack of appropriate
      innate activation rather than to increased systemic immune activation.
      Importantly, patterns of chemoattractant cytokine responses at 24 h and
      alterations in 209 peripheral blood mononuclear cell transcripts at 72 h were
      predictive of subsequent induction and magnitude of HIV-specific CD8(+) T-cell
      responses. This systems approach provides a framework to compare innate responses
      induced by vectors, as shown here by contrasting the more rapid, robust response
      to MRKAd5/HIV with that to yellow fever vaccine. When applied iteratively, the
      findings may permit selection of HIV vaccine candidates eliciting innate immune
      response profiles more likely to drive HIV protective immunity.

PMID- 23151507
TI  - G9a functions as a molecular scaffold for assembly of transcriptional
      coactivators on a subset of glucocorticoid receptor target genes.
AB  - Histone H3 lysine-9 methyltransferase G9a/EHMT2/KMT1C is a key corepressor of
      gene expression. However, activation of a limited number of genes by G9a
      (independent of its catalytic activity) has also been observed, although the
      precise molecular mechanisms are unknown. By using RNAi in combination with gene
      expression microarray analysis, we found that G9a functions as a positive and a
      negative transcriptional coregulator for discrete subsets of genes that are
      regulated by the hormone-activated Glucocorticoid Receptor (GR). G9a was
      recruited to GR-binding sites (but not to the gene body) of its target genes and
      interacted with GR, suggesting recruitment of G9a by GR. In contrast to its
      corepressor function, positive regulation of gene expression by G9a involved G9a
      mediated enhanced recruitment of coactivators CARM1 and p300 to GR target genes.
      Further supporting a role for G9a as a molecular scaffold for its coactivator
      function, the G9a-specific methyltransferase inhibitor UNC0646 did not affect G9a
      coactivator function but selectively decreased G9a corepressor function for
      endogenous target genes. Overall, G9a functioned as a coactivator for hormone
      activated genes and as a corepressor in support of hormone-induced gene
      repression, suggesting that the positive or negative actions of G9a are
      determined by the gene-specific regulatory environment and chromatin
      architecture. These findings indicate distinct mechanisms of G9a coactivator vs.
      corepressor functions in transcriptional regulation and provide insight into the
      molecular mechanisms of G9a coactivator function. Our results also suggest a
      physiological role of G9a in fine tuning the set of genes that respond to
      glucocorticoids.

PMID- 23151508
TI  - p10, the N-terminal domain of p35, protects against CDK5/p25-induced
      neurotoxicity.
AB  - Cyclin-dependent kinase 5(CDK5) in complex with its activator, p35 (protein of 35
      kDa), is essential for early neurodevelopment in mammals. However, endogenous
      cleavage of p35 to p25 is associated with neuron death and neurodegenerative
      disease. Here we show that a peptide (p10') encoding the N-terminal domain of p35
      protects against CDK5/p25-induced toxicity in neurons. p10' also prevented the
      death of neurons treated with the neurotoxin, 1-methyl-4-phenylpyridinium
      (MPP(+)), which induces conversion of endogenous p35 to p25, and Parkinson
      disease (PD)-like symptoms in animals. MPP(+) induces CDK5/p25-dependent
      phosphorylation of peroxiredoxin 2 (Prx2), resulting in inhibition of its
      peroxireductase activity and accumulation of reactive oxygen species (ROS). We
      found that p10' expression inhibited both Prx2 phosphorylation and ROS
      accumulation in neurons. In addition, p10' inhibited the p25-induced appearance
      of antigen of the Ki67 antibody (Ki67) and phosphohistone H2AX (gammaH2AX),
      classic markers of cell cycle activity and DNA double-strand breakage,
      respectively, associated with neuron death. Our results suggest that p10 (protein
      of 10 kDa) is a unique prosurvival domain in p35, essential for normal CDK5/p35
      function in neurons. Loss of the p10 domain results in CDK5/p25 toxicity and
      neurodegeneration in vivo.

PMID- 23151509
TI  - Microbial conversion of choline to trimethylamine requires a glycyl radical
      enzyme.
AB  - Choline and trimethylamine (TMA) are small molecules that play central roles in
      biological processes throughout all kingdoms of life. These ubiquitous
      metabolites are linked through a single biochemical transformation, the
      conversion of choline to TMA by anaerobic microorganisms. This metabolic
      activity, which contributes to methanogenesis and human disease, has been known
      for over a century but has eluded genetic and biochemical characterization. We
      have identified a gene cluster responsible for anaerobic choline degradation
      within the genome of a sulfate-reducing bacterium and verified its function using
      both a genetic knockout strategy and heterologous expression in Escherichia coli.
      Bioinformatics and electron paramagnetic resonance (EPR) spectroscopy revealed
      the involvement of a C-N bond cleaving glycyl radical enzyme in TMA production,
      which is unprecedented chemistry for this enzyme family. Our discovery provides
      the predictive capabilities needed to identify choline utilization clusters in
      numerous bacterial genomes, underscoring the importance and prevalence of this
      metabolic activity within the human microbiota and the environment.

PMID- 23151510
TI  - Cholesterol increases kinetic, energetic, and mechanical stability of the human
      beta2-adrenergic receptor.
AB  - The steroid cholesterol is an essential component of eukaryotic membranes, and it
      functionally modulates membrane proteins, including G protein-coupled receptors.
      To reveal insight into how cholesterol modulates G protein-coupled receptors, we
      have used dynamic single-molecule force spectroscopy to quantify the mechanical
      strength and flexibility, conformational variability, and kinetic and energetic
      stability of structural segments stabilizing the human beta(2)-adrenergic
      receptor (beta(2)AR) in the absence and presence of the cholesterol analog
      cholesteryl hemisuccinate (CHS). CHS considerably increased the kinetic,
      energetic, and mechanical stability of almost every structural segment at
      sufficient magnitude to alter the structure and functional relationship of
      beta(2)AR. One exception was the structural core segment of beta(2)AR, which
      establishes multiple ligand binding sites, and its properties were not
      significantly influenced by CHS.

PMID- 23151511
TI  - The DNA virus Invertebrate iridescent virus 6 is a target of the Drosophila RNAi
      machinery.
AB  - RNA viruses in insects are targets of an RNA interference (RNAi)-based antiviral
      immune response, in which viral replication intermediates or viral dsRNA genomes
      are processed by Dicer-2 (Dcr-2) into viral small interfering RNAs (vsiRNAs).
      Whether dsDNA virus infections are controlled by the RNAi pathway remains to be
      determined. Here, we analyzed the role of RNAi in DNA virus infection using
      Drosophila melanogaster infected with Invertebrate iridescent virus 6 (IIV-6) as
      a model. We show that Dcr-2 and Argonaute-2 mutant flies are more sensitive to
      virus infection, suggesting that vsiRNAs contribute to the control of DNA virus
      infection. Indeed, small RNA sequencing of IIV-6-infected WT and RNAi mutant
      flies identified abundant vsiRNAs that were produced in a Dcr-2-dependent manner.
      We observed a highly uneven distribution with strong clustering of vsiRNAs to
      small defined regions (hotspots) and modest coverage at other regions
      (coldspots). vsiRNAs mapped in similar proportions to both strands of the viral
      genome, suggesting that long dsRNA derived from convergent overlapping
      transcripts serves as a substrate for Dcr-2. In agreement, strand-specific RT-PCR
      and Northern blot analyses indicated that antisense transcripts are produced
      during infection. Moreover, we show that vsiRNAs are functional in silencing
      reporter constructs carrying fragments of the IIV-6 genome. Together, our data
      indicate that RNAi provides antiviral defense against dsDNA viruses in animals.
      Thus, RNAi is the predominant antiviral defense mechanism in insects that
      provides protection against all major classes of viruses.

PMID- 23151512
TI  - Highly efficient full-length hepatitis C virus genotype 1 (strain TN) infectious
      culture system.
AB  - Chronic infection with hepatitis C virus (HCV) is an important cause of end stage
      liver disease worldwide. In the United States, most HCV-related disease is
      associated with genotype 1 infection, which remains difficult to treat. Drug and
      vaccine development was hampered by inability to culture patient isolates
      representing HCV genotypes 1-7 and subtypes; only a recombinant 2a genome (strain
      JFH1) spontaneously replicated in vitro. Recently, we identified three mutations
      F1464L/A1672S/D2979G (LSG) in the nonstructural (NS) proteins, essential for
      development of full-length HCV 2a (J6) and 2b (J8) culture systems in Huh7.5
      cells. Here, we developed a highly efficient genotype 1a (strain TN) full-length
      culture system. We initially found that the LSG substitutions conferred viability
      to an intergenotypic recombinant composed of TN 5' untranslated region (5'UTR)
      NS5A and JFH1 NS5B-3'UTR; recovered viruses acquired two adaptive mutations
      located in NS3 and NS4B. Introduction of these changes into a replication
      deficient TN full-length genome, harboring LSG, permitted efficient HCV
      production. Additional identified NS4B and NS5B mutations fully adapted the TN
      full-length virus. Thus, a TN genome with 8 changes (designated TN cell-culture
      derived, TNcc) replicated efficiently and released infectious particles of ~5
      log(10) focus-forming units per mL; passaged TNcc did not require additional
      changes. IFN-alpha and directly acting antivirals targeting the HCV protease,
      NS5A, and NS5B, each inhibited full-length TN infection dose-dependently. Given
      the unique importance of genotype 1 for pathogenesis, this infectious 1a culture
      system represents an important advance in HCV research. The approach used and the
      mutations identified might permit culture development for other HCV isolates,
      thus facilitating vaccine development and personalized treatment.

PMID- 23151513
TI  - A model system for mitochondrial biogenesis reveals evolutionary rewiring of
      protein import and membrane assembly pathways.
AB  - The controlled biogenesis of mitochondria is a key cellular system coordinated
      with the cell division cycle, and major efforts in systems biology currently are
      directed toward understanding of the control points at which this coordination is
      achieved. Here we present insights into the function, evolution, and regulation
      of mitochondrial biogenesis through the study of the protein import machinery in
      the human fungal pathogen, Candida albicans. Features that distinguish C.
      albicans from baker's yeast (Saccharomyces cerevisiae) include the stringency of
      metabolic control at the level of oxygen consumption, the potential for ATP
      exchange through the porin in the outer membrane, and components and domains in
      the sorting and assembling machinery complex, a molecular machine that drives the
      assembly of proteins in the outer mitochondrial membrane. Analysis of targeting
      sequences and assays of mitochondrial protein import show that components of the
      electron transport chain are imported by distinct pathways in C. albicans and S.
      cerevisiae, representing an evolutionary rewiring of mitochondrial import
      pathways. We suggest that studies using this pathogen as a model system for
      mitochondrial biogenesis will greatly enhance our knowledge of how mitochondria
      are made and controlled through the course of the cell-division cycle.

PMID- 23151514
TI  - Strong signatures of selection in the domestic pig genome.
AB  - Domestication of wild boar (Sus scrofa) and subsequent selection have resulted in
      dramatic phenotypic changes in domestic pigs for a number of traits, including
      behavior, body composition, reproduction, and coat color. Here we have used whole
      genome resequencing to reveal some of the loci that underlie phenotypic evolution
      in European domestic pigs. Selective sweep analyses revealed strong signatures of
      selection at three loci harboring quantitative trait loci that explain a
      considerable part of one of the most characteristic morphological changes in the
      domestic pig--the elongation of the back and an increased number of vertebrae.
      The three loci were associated with the NR6A1, PLAG1, and LCORL genes. The latter
      two have repeatedly been associated with loci controlling stature in other
      domestic animals and in humans. Most European domestic pigs are homozygous for
      the same haplotype at these three loci. We found an excess of derived
      nonsynonymous substitutions in domestic pigs, most likely reflecting both
      positive selection and relaxed purifying selection after domestication. Our
      analysis of structural variation revealed four duplications at the KIT locus that
      were exclusively present in white or white-spotted pigs, carrying the Dominant
      white, Patch, or Belt alleles. This discovery illustrates how structural changes
      have contributed to rapid phenotypic evolution in domestic animals and how
      alleles in domestic animals may evolve by the accumulation of multiple causative
      mutations as a response to strong directional selection.

PMID- 23151516
TI  - Effects of corticotropin-releasing factor on intermediolateral cell column
      neurons of newborn rats.
AB  - Corticotropin-releasing factor (CRF) is a neuropeptide that mediates
      neuroendocrine, autonomic, and behavioral processes associated with the stress
      response. CRF-containing fibers and receptors are found in various regions of the
      central nervous system including the spinal cord. Here, we report excitatory
      effects of CRF on sympathetic preganglionic neurons in the intermediolateral cell
      column (IML) of in vitro spinal cord preparations from newborn rats. We also
      examine the receptor subtypes that are involved in the CRF effects. Application
      of CRF significantly depolarized the IML neurons and increased the frequency of
      excitatory postsynaptic potentials (EPSPs) in the IML neurons. These effects were
      blocked by the CRF receptor 1 antagonist, antalarmin. Menthol, a transient
      receptor potential channel M8 agonist, depressed EPSPs enhanced by CRF. Our
      findings suggested that CRF depolarized the IML neurons via direct postsynaptic
      action and CRF-affected interneurons located in the spinal cord send EPSPs to IML
      neurons. These excitatory effects of CRF may be caused through CRF1 receptors but
      not CRF2 receptors.

PMID- 23151515
TI  - New insights into the effects of age and sex on arterial baroreflex function at
      rest and during dynamic exercise in humans.
AB  - The arterial baroreflex (ABR) performs an important role in regulating blood
      pressure (BP) both at rest and during exercise, by carefully orchestrating
      autonomic neural activity to the heart and blood vessels. Reduced ABR sensitivity
      (i.e., gain) has been associated with increased cardiovascular risk, cardiac
      electrical instability and orthostatic intolerance, while 'normal' ABR function
      during exercise is important for ensuring an appropriate cardiovascular response
      is elicited. Previous studies examining the influence of age and sex on resting
      ABR function in humans have primarily used pharmacological methods (e.g.,
      modified Oxford technique) to change BP and alter baroreceptor input. With this
      approach only reflex control of heart rate and sympathetic nerve activity may be
      evaluated, and as such the influence of age and sex on ABR control of BP per se
      remains incompletely understood. Furthermore, the majority of previous studies
      examining ABR function during exercise have principally assessed young men.
      Whether these findings can be extrapolated to young women or older men and women
      remains unclear. Recently the potential for age and sex to modulate the
      integrative neural control of the cardiovascular system is becoming appreciated.
      This review article will provide a detailed update of such recent advances into
      our understanding of the effects of age and sex on ABR control of BP both at rest
      and during dynamic exercise in humans.

PMID- 23151517
TI  - Stimulation of adult resident cardiac progenitor cells by durable myocardial
      expression of thymosin beta 4 with ultrasound-targeted microbubble delivery.
AB  - It has been proposed that thymosin beta 4 (TB4)-protein delivery stimulates
      differentiation of resident adult WT1-positive cardiac progenitor cells, but with
      very low efficiency. We determined whether gene therapy with human TB4 stimulates
      proliferation of resident adult cardiac progenitor cells in normal rat heart.
      Ultrasound-targeted microbubble destruction (UTMD) was used to deliver the human
      TB4 gene under a piggybac transposon plasmid to normal rat heart. The rat hearts
      were assayed by quantitative reverse transcription-PCR and immunohistology with a
      confocal microscope at 1, 2, 3, 4 and 12 weeks after UTMD. Exogenous TB4
      stimulation resulted in the presence of WT1-positive cardiac progenitor cells
      from epicardium to endocardium. TB4 stimulated angiogenesis and arteriogenesis.
      One month after TB4 gene therapy by UTMD, the percentage of NKX2.5-positive
      cardiomyocytes was 5.5+/-1.0% and NKX2.5 mRNA was 24-fold higher than in the
      control groups (P<0.001). Similar results were found for ISL-1, BrDu, Ki-67, PHH3
      and aurora B (P<0.001). Cardiac-specific delivery of exogenous human TB4 gene
      efficiently stimulates proliferation and differentiation of resident WT1-positive
      adult cardiac progenitor cells into three intact cardiac cell lineages-vascular
      endothelial cells, coronary artery smooth muscle cells and cardiac muscle cells
      in normal adult rat heart.

PMID- 23151518
TI  - Intramyocardial transfer of hepatocyte growth factor as an adjunct to CABG: phase
      I clinical study.
AB  - The purpose of this phase I clinical trial was to evaluate the safety,
      tolerability and potential efficacy of VM202, naked DNA expressing two isoforms
      of hepatocyte growth factor, as an adjunct therapy to coronary artery bypass
      grafting (CABG) in patients with ischemic heart disease (IHD). Nine patients were
      assigned to receive increasing doses (0.5 to 2.0 mg) of VM202 injected into the
      right coronary artery (RCA) territory following completion of CABG for the left
      coronary artery territory. Patients were evaluated for safety and tolerability,
      and changes in myocardial functions were monitored via echocardiography, cardiac
      magnetic resonance imaging and myocardial single photon emission computed
      tomography throughout 6-month follow-up period. No serious complication related
      to VM202 was observed throughout the 6-month follow-up period. Global myocardial
      functions (wall motion score index, P=0.0084; stress perfusion, P=0.0002)
      improved during the follow-up period. In the RCA region, there was an increase in
      the stress perfusion (baseline vs 3-month, P=0.024; baseline vs 6-month, P=0.024)
      and also in the wall thickness of the diastolic and systolic phases.
      Intramyocardial injection of VM202 can be safely used in IHD patients with the
      tolerable dose of 2.0 mg. In addition, VM202 might appear to have improved
      regional myocardial perfusion and wall thickness in the injected region.

PMID- 23151519
TI  - Hairpin-end conformation of adeno-associated virus genome determines interactions
      with DNA-repair pathways.
AB  - The palindromic terminal repeats (TRs) of adeno-associated virus (AAV) form DNA
      hairpins (HPs) are essential for replication and for priming the conversion of
      single-stranded virion DNA to double strand. In recombinant AAV (rAAV) gene
      delivery vectors, they are targets for the DNA-repair pathways leading to
      circularization, concatemerization and, infrequently, chromosomal integration. We
      investigated the effect of the TR HP on recombination by comparing specific DNA
      substrates transfected into wild-type and DNA-repair-deficient cells. DNA
      molecules with the TR sequences constrained in the T-shaped HP conformation at
      one or both ends were subject to a loss of gene expression, which was partially
      relieved in ataxia telangiectasia mutated (ATM(-/-)) cells. The ATM-dependent
      effect was mediated by transcriptional silencing of a subset of HP-containing
      molecules in cis rather than a loss of DNA, and was dependent on the specific T
      shaped structure of the HP and not the primary sequence. DNA molecules with
      simple U-shaped HP ends were unaffected by ATM-dependent silencing. The silenced
      molecules remained in a linear conformation, in contrast to the expressed
      molecules, which were circularized. In the absence of ATM activity, this subset
      remained linear but was actively expressed. DNA molecules with the TR sequence in
      the open duplex conformation, or without TR sequences, were unaffected by ATM
      mutation and were predominantly converted to circular forms. A separate HP
      specific effect in normal cells resulted in a loss of DNA substrate in the
      nucleus and was ATM independent. These results suggest that the presence of the
      HP structure on rAAV vector genomes subjects them to specific, and sometimes
      unproductive, DNA-repair/recombination pathways.

PMID- 23151521
TI  - In vivo delivery of DN:REST improves transcriptional changes of REST-regulated
      genes in HD mice.
AB  - Current therapeutic strategies for Huntington's disease (HD) are focused on
      symptom management of disease progression. Transcriptional dysregulation is one
      of the major characteristics in HD. REST is a transcriptional repressor that
      silences gene expression through binding to RE1/NRSE sites found in the
      regulatory regions of numerous neuronal genes. Dysregulation of REST and its
      targeted genes has been reported in different cell and mouse HD models, as well
      as in biopsies from human patients. In this work, we characterized
      transcriptional dysregulation associated with REST in two different HD mouse
      models and assessed the therapeutic effect of interfering with REST function by
      overexpressing a dominant-negative form (DN:REST). We show that delivery of
      DN:REST in the motor cortex restores brain-derived neurotrophic factor (BDNF)
      mRNA and protein levels by reducing endogenous REST occupancy at the Bdnf locus.
      Similarly, expression of other REST-regulated genes such as Synapsin I (Syn1),
      Proenkephalin (Penk1) and Cholinergic receptor muscarinic 4 (Chrm4) were restored
      to normal levels while non-REST-regulated genes were unaffected. This is the
      first study conducted to investigate REST's role in vivo in a neurodegenerative
      disease. Our data show that DN:REST in motor cortex reversed RESTs repressive
      effects on target genes. However, the lack of therapeutic effect on motor
      function suggests that a more widespread rescue of REST-regulated sites in the
      affected brain regions may be necessary.

PMID- 23151520
TI  - scAAV-mediated gene transfer of interleukin-1-receptor antagonist to synovium and
      articular cartilage in large mammalian joints.
AB  - With the long-term goal of developing a gene-based treatment for osteoarthritis
      (OA), we performed studies to evaluate the equine joint as a model for adeno
      associated virus (AAV)-mediated gene transfer to large, weight-bearing human
      joints. A self-complementary AAV2 vector containing the coding regions for human
      interleukin-1-receptor antagonist (hIL-1Ra) or green fluorescent protein was
      packaged in AAV capsid serotypes 1, 2, 5, 8 and 9. Following infection of human
      and equine synovial fibroblasts in culture, we found that both were only
      receptive to transduction with AAV1, 2 and 5. For these serotypes, however,
      transgene expression from the equine cells was consistently at least 10-fold
      higher. Analyses of AAV surface receptor molecules and intracellular trafficking
      of vector genomes implicate enhanced viral uptake by the equine cells. Following
      delivery of 1 * 10(11) vector genomes of serotypes 2, 5 and 8 into the forelimb
      joints of the horse, all three enabled hIL-1Ra expression at biologically
      relevant levels and effectively transduced the same cell types, primarily
      synovial fibroblasts and, to a lesser degree, chondrocytes in articular
      cartilage. These results provide optimism that AAV vectors can be effectively
      adapted for gene delivery to large human joints affected by OA.

PMID- 23151522
TI  - Better services . . . are we there yet?

PMID- 23151523
TI  - Inputs and outcomes: what do staff in services for people with intellectual
      disabilities perceive they bring to and receive from their work-based
      relationships?
AB  - A number of studies involving staff working in services for people with
      intellectual disabilities have utilised equity theory as a theoretical framework.
      According to this theory, people evaluate social relationships through the
      comparison of inputs and outcomes, respectively, with what a person brings to and
      receives from a relationship. Little is known about what constitute inputs and
      outcomes for staff working in services for people with intellectual disabilities.
      Semi-structured interviews were conducted with 15 staff to find out what
      constitute inputs and outcomes for staff who work with people with intellectual
      disabilities. The interviews were conducted in the first half of 2008 in the
      United Kingdom. Data were analysed using template analysis. A wide range of
      inputs and outcomes was identified by staff, which were grouped under high-level
      themes relating to relationships with their employers, their co-workers and the
      service users. The utility of the findings, in terms of informing future
      research, is discussed.

PMID- 23151525
TI  - Propranolol inhibits endothelial progenitor cell homing: a possible treatment
      mechanism of infantile hemangioma.
AB  - BACKGROUND: Propranolol effectively treats infantile hemangioma, but its
      mechanisms of action remain poorly understood. Although the antiangiogenesis role
      of propranolol has been previously demonstrated, several lines of evidence
      suggest that this therapeutic agent may affect the neovascular formation in
      infantile hemangioma by targeting vasculogenesis. In addition, the homing of
      endothelial progenitor cells to the lesion of infantile hemangioma plays an
      important role during the process of vasculogenesis. The purpose of this study
      was to investigate whether propranolol inhibits the vasculogenesis in infantile
      hemangioma by targeting endothelial progenitor cells recruitment. METHODS:
      Endothelial progenitor cells were treated with different concentrations (0, 1, 5,
      10, 20, 40, 60, 80, 100 MUM) of propranolol for indicated times (24, 48, 72 h).
      Cell proliferation and viability were assessed by MTT assay and trypan blue
      staining. Cell migration was determined by wound healing assay and Boyden chamber
      assay. The expression levels of extracellular signal regulated kinase, phospho
      extracellular signal regulated kinase, Akt, and phospho-Akt were measured by
      Western blot analysis to explore the molecular mechanism of propranolol on
      endothelial progenitor cells. In addition, the expression of CXCR4 was measured
      by Western blot and reverse transcriptase polymerase chain reaction. RESULTS:
      Propranolol did not significantly affect the proliferation of endothelial
      progenitor cells. It inhibited stromal-cell-derived factor 1alpha-induced
      migration of endothelial progenitor cells through the Akt and MAPK pathways and
      the expression of CXCR4 in a dose- and time-dependent manner. In addition, the
      expression of CXCR4 was suppressed by propranolol most likely through the Akt and
      MAPK pathways. CONCLUSIONS: Propranolol inhibits stromal-cell-derived factor
      1alpha-induced endothelial progenitor cell homing by suppressing the expression
      of CXCR4 most likely through the Akt and MAPK pathways.

PMID- 23151526
TI  - Organ specific complement proteins inhibition can reduce the risk of
      antiphospholipid antibodies mediated fetal loss.
AB  - Antiphospholipid syndrome is a pregnancy related, systemic autoimmune disorder in
      which antibodies directed against cell membrane phospholipids with multiple
      venous/arterial thromboses. Though the etiology of antiphospholipid syndrome has
      not been identified exactly, experimental evidences suggest the possible
      mechanisms involved in the pathogenicity of this syndrome. Antiphospholipid
      antibodies mediate deposition of complement proteins in placenta and over
      expression of tissue factor on the surface of neutrophils which are reported to
      be the prominent cause of prothrombotic phenotype. The activation complement
      components C3 and C5 by antiphospholipid antibodies would eventually activates
      blood coagulation pathway that leads to thrombosis. Inhibition of activated
      complement components C3a and C5a by anticomplement agents protects from
      antiphospholipid antibody mediated fetal loss. Since the interference of
      complement pathway may lead to deleterious effects, we hypothesis that local
      inhibition of complement proteins C3a and C5a at placenta would reduce the risk
      of antiphospholipid antibody mediated placental thrombosis and pregnancy
      complications.

PMID- 23151527
TI  - Association of glucocorticoid receptor gene NR3C1 genetic variants with
      angiographically documented coronary artery disease and its risk factors.
AB  - BACKGROUND AND AIMS: Glucocorticoids and their receptors are involved in
      inflammation and many cardiovascular risk factors. We examined associations of
      Tth111I, N363S and ER22/23EK NR3C1 gene polymorphisms and haplotypes, with
      coronary artery disease (CAD), severity of CAD (single-vessel vs. multivessel
      disease) and risk factors. METHODS: Three hundred ten individuals were submitted
      to coronary angiography. Selected genotypes were determined by PCR-RFLP. RESULTS:
      Carriers of the Tth111I allele T were found significantly less often in the CAD
      compared with the non-CAD group (49.7 vs. 64.6%, p = 0.013); this association was
      similar for TGA haplotype carriers (49.2 vs. 62.8%, p = 0.024); the T allele was
      more frequent in females (66.3 vs. 51.1%, p = 0.020) and its presence was
      associated with higher levels of HDL-cholesterol (46.6 +/- 12.7 vs. 43.5 +/- 10.1
      mg/dL for T-carriers vs. noncarriers, p = 0.045). The TT genotype proved to be
      less common in MVD than SVD (5.9 vs. 14.1%, p = 0.075). The 363S allele was
      significantly associated with diabetes mellitus (DM) (24.4 vs. 10.9%; carriers in
      DM and non-DM subjects, respectively, p = 0.027), the TT genotype or TGA/TGA
      diplotype (in which the 363S allele was absent) were less frequent in DM than in
      non-DM subjects (p = 0.012 for Tth111I-TT and p = 0.020 for TGA/TGA diplotype).
      No significant associations between CAD and N363S or ER22/23EK polymorphisms were
      found. CONCLUSIONS: Our results suggest that the Tth111I NR3C1 polymorphism may
      play a protective role in the development of CAD, and homozygous TT in
      development of MVD. The N363S polymorphisms may contribute to the development of
      diabetes in the Polish population.

PMID- 23151528
TI  - Russian war surgery in 1812: 200 years since Russia's war triumph.
AB  - Specific wounds inflicted on soldiers and officers of the Russian Army by French
      firearms and cold weapon and wound treatment by Russian surgeons during 1812
      Napoleon's invasion (better known in Russia as the Patriotic War of 1812) are
      discussed. An inference is made that the then surgical treatment was not only
      administered at a high level but was also versatile and efficient and thus could
      make a certain contribution to the victory of the Russian arms.

PMID- 23151529
TI  - Age-related changes in physical examination and gait parameters in normally
      developing children and adolescents.
AB  - This study aimed to examine the correlations between physical examinations and
      gait kinematics, and age-related changes in 47 normally developing children.
      Physical examinations were not found to be significantly correlated with
      kinematics, except for Thomas and Staheli tests. Unilateral and bilateral
      popliteal angles decreased significantly by 2.2 and 1.6 degrees  per annum, and
      ankle dorsiflexion with knee extension and 90 degrees  flexion decreased
      significantly by 0.7 and 0.8 degrees . Physical examinations and gait parameters
      might represent different dimensions of gait, and care should be taken when
      assessing gait problems. Age-related changes should be considered when
      interpreting physical examination and gait kinematics for surgery.

PMID- 23151530
TI  - A clocked finite state machine built from DNA.
AB  - We implement a finite state machine by representing state, transition rules and
      input symbols with DNA components. Transitions between states are triggered by a
      clock signal which allows synchronized, parallel operation of two (or more) state
      machines. The state machine can be re-programmed by changing the input symbols.

PMID- 23151531
TI  - Folate in pregnancy and imprinted gene and repeat element methylation in the
      offspring.
AB  - BACKGROUND: Epigenetic regulation of imprinted genes and transposable elements
      has been implicated in human disease and may be affected by maternal diet.
      OBJECTIVE: The objective was to determine the effect on offspring epigenetic
      status of nutritional and genetic factors that influence folate exposure in
      pregnancy. DESIGN: We measured folate intake from diet, the use of folic acid
      supplements and the period of consumption, maternal and cord red blood cell (RBC)
      folate, and genotypes for 5 methylation cycle enzymes in a prospective cohort
      study of pregnancies in the United Kingdom between 2000 and 2006. We related
      these to offspring methylation status within 3 maternally methylated imprinted
      genes: paternally expressed gene 3 (PEG3), insulin-like growth factor 2 (IGF2),
      and small nuclear ribonucleoprotein polypeptide N, and the long interspersed
      nuclear element 1 (LINE-1) in genomic DNA extracted from whole blood in 913
      pregnancies. RESULTS: Supplement use after 12 wk of gestation was associated with
      a higher level of methylation in IGF2 (+0.7%; 95% CI: 0.02, 1.4; P = 0.044) and
      reduced methylation in both PEG3 (-0.5%; 95% CI: -0.9, -0.1; P = 0.018) and LINE
      1 (-0.3%; 95% CI: -0.6, -0.04; P = 0.029). The same pattern was observed in
      relation to RBC folate in the cord blood at birth: IGF2 (P = 0.038), PEG3 (P <
      0.001), and LINE-1 (P < 0.001). LINE-1 methylation was related to maternal RBC
      folate (P = 0.001) at 19 wk. No effect of supplement use up to 12 wk (current
      recommendation) was found. CONCLUSIONS: Folic acid use after 12 wk of gestation
      influences offspring repeat element and imprinted gene methylation. We need to
      understand the consequences of these epigenetic effects.

PMID- 23151532
TI  - Effects of vitamin A and beta-carotene supplementation on birth size and length
      of gestation in rural Bangladesh: a cluster-randomized trial.
AB  - BACKGROUND: Micronutrient deficiencies may be related to poor fetal growth and
      short gestation. Few studies have investigated the contribution of maternal
      vitamin A deficiency to these outcomes. OBJECTIVE: In rural northwestern
      Bangladesh, we examined the effects of weekly antenatal vitamin A and beta
      carotene supplementation on birth weight, length, circumferential body measures,
      and length of gestation. DESIGN: With the use of a cluster-randomized, placebo
      controlled trial design, pregnant women were enrolled in the first trimester and
      began receiving their allocated supplements (vitamin A, beta-carotene, or
      placebo) weekly until 3 mo postpartum. Birth anthropometric measures were made at
      home. RESULTS: Of 13,709 newborns whose birth weight was measured within 72 h of
      birth, mean (+/-SD) weight was 2.44 +/- 0.42 kg, the prevalence of low birth
      weight (LBW) was 54.4%, and that of small-for-gestational age (SGA) was 70.5%.
      Birth weight, length, and chest, head, and arm circumferences did not differ
      between supplementation and placebo groups nor did rates of LBW and SGA. Mean
      gestational age at birth was 38.3 +/- 2.9 wk, and 25.6% of births occurred before
      37 wk. Neither gestational age nor preterm birth rate differed with vitamin A or
      beta-carotene supplementation. CONCLUSIONS: In this rural South Asian population
      with a high burden of LBW and preterm birth but modest levels of maternal vitamin
      A deficiency, antenatal vitamin A or beta-carotene supplementation did not
      benefit these birth outcomes. Other nutritional and nonnutritional interventions
      should be examined to reduce risks of these adverse outcomes in rural South Asia.
      This trial was registered at clinicaltrials.gov as NCT00198822.

PMID- 23151533
TI  - Increased intestinal absorption by segmental reversal of the small bowel in adult
      patients with short-bowel syndrome: a case-control study.
AB  - BACKGROUND: Segmental reversal of the small bowel (SRSB) is proposed in patients
      with short-bowel syndrome (SBS) as a rehabilitative therapy, but its effects on
      absorption have not been studied. OBJECTIVE: We aimed to determine intestinal
      macronutrient absorption and home parenteral nutrition (HPN) dependence in SBS
      patients with intestinal failure. DESIGN: We included in a retrospective study
      all consecutive patients who had an SRSB between 1985 and 2010 and underwent a
      study of macronutrient absorption. Patients were matched to SBS controls with the
      same digestive characteristics. Energy and macronutrient absorption were
      measured. The dependence on HPN was expressed by the number of infusions per week
      and by the calories infused daily divided by the basal energy expenditure
      multiplied by 1.5. RESULTS: Seventeen patients who had an SRSB were matched to 17
      control patients. Intestinal absorption was higher in the SRSB group for total
      calories (69.5% compared with 58.0%), fat (48.4% compared with 33.2%), and
      protein (62.7% compared with 53.4%) (P < 0.05). Median oral autonomy was 100% +/-
      38.4% in the SRSB group, whereas it was 79% +/- 39.6% in the control group (P <
      0.05). The number of calories infused was lower in the SRSB group (500 +/- 283
      compared with 684 +/- 541; P < 0.05), as was HPN dependence (33% +/- 20% compared
      with 48% +/- 38%; P < 0.05) at the time of the study. CONCLUSION: SRSB allows a
      gain in macronutrient absorption, which is associated with a lower HPN
      dependence. To our view, SRSB should be integrated in intestinal rehabilitative
      adult programs.

PMID- 23151534
TI  - Fetal growth, omega-3 (n-3) fatty acids, and progression of subclinical
      atherosclerosis: preventing fetal origins of disease? The Cardiovascular Risk in
      Young Finns Study.
AB  - BACKGROUND: Impaired fetal growth is independently associated with an increased
      risk of cardiovascular events in adulthood. Prevention strategies that can be
      implemented during adulthood have not been identified. OBJECTIVE: The objective
      was to determine whether habitual omega-3 (n-3) fatty acid intake is associated
      with the rate of increase of carotid intima-media thickness during adulthood in
      individuals with impaired fetal growth. DESIGN: This was a population-based,
      prospective cohort study of 1573 adults in Finland. Carotid intima-media
      thickness was assessed in 2001 (at ages 24-39 y) and in 2007. Participants were
      categorized as having had impaired fetal growth (term birth with birth weight
      <10th percentile for sex or preterm birth with birth weight <25th percentile for
      gestational age and sex; n = 193) or normal fetal growth (all other participants;
      n = 1380). Omega-3 fatty acid intake was assessed by using a food-frequency
      questionnaire and on the basis of serum fatty acid concentrations. RESULTS: In
      multivariable models, the 6-y progression of carotid intima-media thickness was
      inversely associated with dietary omega-3 fatty acids in those with impaired
      fetal growth (P = 0.04). Similarly, serum omega-3 fatty acid concentrations were
      inversely associated with the 6-y progression of carotid intima-media thickness
      in those with impaired fetal growth (P = 0.04) but were not noted in those with
      normal fetal growth (P = 0.94 and P = 0.26, respectively). CONCLUSION: Dietary
      intake of omega-3 fatty acids is associated with a slower rate of increase in
      carotid intima-media thickness in those with impaired fetal growth.

PMID- 23151535
TI  - Caffeinated and caffeine-free beverages and risk of type 2 diabetes.
AB  - BACKGROUND: Consumption of caffeinated beverages such as coffee and tea has been
      associated with a lower risk of type 2 diabetes (T2D). Paradoxically, short-term
      metabolic studies have shown that caffeine impairs postprandial glycemic control.
      OBJECTIVE: The objective was to prospectively examine the association of
      caffeinated compared with caffeine-free beverages, including coffee, tea, sugar
      sweetened beverages (SSBs), and carbonated artificially sweetened beverages
      (ASBs), with T2D risk. DESIGN: We prospectively observed 74,749 women from the
      Nurses' Health Study (NHS, 1984-2008) and 39,059 men from the Health
      Professionals Follow-Up Study (HPFS, 1986-2008) who were free of diabetes,
      cardiovascular diseases, and cancer at baseline. RESULTS: We documented 7370
      incident cases of T2D during 24 y of follow-up in the NHS and 2865 new cases
      during 22 y of follow-up in the HPFS. After major lifestyle and dietary risk
      factors were controlled for, caffeinated and caffeine-free SSB intake was
      significantly associated with a higher risk of T2D in the NHS (RR per serving:
      13% for caffeinated SSBs, 11% for caffeine-free SSBs; P < 0.05) and in the HPFS
      (RR per serving: 16% for caffeinated SSBs, 23% for caffeine-free SSBs; P < 0.01).
      Only caffeine-free ASB intake in NHS participants was associated with a higher
      risk of T2D (RR: 6% per serving; P < 0.001). Conversely, the consumption of
      caffeinated and decaffeinated coffee was associated with a lower risk of T2D [RR
      per serving: 8% for both caffeinated and decaffeinated coffee in the NHS (P <
      0.0001) and 4% for caffeinated and 7% for decaffeinated coffee in the HPFS (P <
      0.01)]. Only caffeinated tea was associated with a lower T2D risk among NHS
      participants (RR per serving: 5%; P < 0.0001). CONCLUSION: Irrespective of the
      caffeine content, SSB intake was associated with a higher risk of T2D, and coffee
      intake was associated with a lower risk of T2D.

PMID- 23151536
TI  - Supplementation with 1000 IU vitamin D/d leads to parathyroid hormone
      suppression, but not increased fractional calcium absorption, in 4-8-y-old
      children: a double-blind randomized controlled trial.
AB  - BACKGROUND: The effects of vitamin D supplementation in healthy prepubertal
      children on physiologic outcomes have not been investigated. OBJECTIVE: The
      objective was to evaluate the effects of supplementation with 1000 IU vitamin
      D(3)/d on calcium absorption. DESIGN: In a double-blind, placebo-controlled
      trial, we randomly assigned 64 children to 1000 IU vitamin D(3)/d (n = 32) or
      placebo (n = 32) for 8 wk. Stable isotopes were used to assess calcium
      absorption. The main outcome measure was calcium absorption before and after
      supplementation. RESULTS: All of the data are shown as means +/- SDs. At
      baseline, vitamin D intake was 221 +/- 79 IU/d and calcium intake was 830 +/- 197
      mg/d. Baseline serum 25-hydroxyvitamin D [25(OH)D] was not significantly
      correlated with fractional or total calcium absorption. After 8 wk, with baseline
      values used as a covariate, no differences were seen in fractional or total
      calcium absorption based on supplementation group (P = 0.75 and 0.36,
      respectively). Supplemented children had a significant increase in 25(OH)D
      concentrations (from 27.7 +/- 7.4 to 36.0 +/- 10.3 ng/mL; P < 0.0001) and a
      decrease in parathyroid hormone (from 21.4 +/- 10.4 to 12.9 +/- 7.1 pg/mL; P <
      0.001); no significant changes in the placebo group were observed. No adverse
      side effects were noted in either group. CONCLUSIONS: Vitamin D(3)
      supplementation at 1000 IU/d increases 25(OH)D and decreases parathyroid hormone
      in children with average vitamin D intakes below the dietary recommendations of
      the Institute of Medicine. However, no significant effects of this change on
      calcium absorption occurred. This trial was registered at clinicaltrials.gov as
      NCT 00868738.

PMID- 23151538
TI  - In vitro protein digestibility and physico-chemical properties of flours and
      protein concentrates from two varieties of lentil (Lens culinaris).
AB  - The chemical composition of whole lentil flours and lentil protein concentrates
      prepared by alkaline extraction and iso-electric precipitation from Blaze and
      Laird varieties of lentil were studied. The protein composition of the flours and
      concentrates, determined by sodium dodecyl sulphate polyacrylamide gel
      electrophoresis (SDS-PAGE) and size-exclusion high-performance liquid
      chromatography (SE-HPLC) showed that the extracted proteins were composed mainly
      of globulins and albumins. Trypsin inhibitor activity ranged between 0.94 and
      1.94 trypsin inhibitor units (TIU) mg(-1) for the flours, but was markedly lower
      in the protein concentrates ranging between 0.17 and 0.66 TIU mg(-1). In vitro
      protein digestibility ranged between 75.90 and 77.05% for the flours, whereas
      significantly (P < 0.05) higher values, ~82.80 to 83.20%, were determined for the
      concentrates. Significant (P < 0.05) differences in colour (DeltaE) were observed
      between the flours and the concentrates from both varieties. Thermal properties
      of both flours as studied by differential scanning calorimetry (DSC) were
      comparable. However, the endothermic parameters of the two protein concentrates
      were significantly (P < 0.05) different. Overall, the results show that in vitro
      protein digestibility of lentil protein concentrates is higher than that of the
      flours, however, both lentil flours and protein concentrates contain useful
      proteins that could serve as value-added ingredients in food formulations.

PMID- 23151537
TI  - Simulating light transport through skin for color prediction of port wine stain
      lesions: a review.
AB  - A survey of the literature is presented regarding the simulation of port wine
      stain (PWS) skin color. Knowledge of PWS features, such as the depths and
      diameters of affected vessels, is essential for informing laser treatment. These
      may be determined through the inverse application of a skin model. The techniques
      which have been applied to achieve this are analyzed in detail. Radiative
      transfer (RT) is found to be the preferred method of simulation. By far the most
      common approximations to RT are the diffusion approximations, which have been
      applied successfully in the past and Monte Carlo techniques, which are now the
      methods of choice. As the requirements for improvement of laser treatment on an
      individual basis continues, the needs for further work towards accurate
      estimations of individual optical coefficients and robust, flexible simulation
      techniques are identified.

PMID- 23151539
TI  - Hetero-metal cation control of CuO nanostructures and their high catalytic
      performance for CO oxidation.
AB  - A controllable synthesis of various morphologies of CuO nanostructures with
      tuning by hetero-metal cations has been developed in aqueous solution at room
      temperature. The morphologies of CuO can be engineered from nanosheets to
      nanoparticles with different length ratios of the long axis to the short axis.
      The formation of many metal-ion complexes plays an important role in slowing the
      release rate of OH(-) and affects the reaction kinetics further. We found that
      the effect of hetero-metal cations on the final morphology of the CuO
      nanostructures was the same as that of the cooling temperature. A series of
      temperature-controlled experiments demonstrated this. Furthermore, among all the
      synthesized CuO nanostructures, the fascinating colloidal mesoporous CuO quasi
      monocrystalline nanosheets prepared at 25  degrees C with a thickness of ca. 10
      nm and large specific surface area of 80.32 m(2) g(-1) is investigated
      intensively. These CuO nanosheets demonstrate a superior catalytic activity for
      CO oxidation, with features of high CO conversion efficiency (47.77 mmol(CO) g(
      1)(CuO) h(-1) at 200  degrees C), which is close to that reported for previously
      investigated supported-CuO catalysts, and a low apparent activation energy E(a)
      (53.3 kJ mol(-1)).

PMID- 23151540
TI  - Dysbiosis of bifidobacteria and Clostridium cluster XIVa in the cystic fibrosis
      fecal microbiota.
AB  - BACKGROUND: Recurrent antimicrobial interventions and disease-related intestinal
      dysfunction are suspected to contribute to the dysbiosis of the gastrointestinal
      microbial ecosystem in patients with cystic fibrosis (CF). The present study set
      out to detect and identify microbial discriminants in the gut microbiota
      composition that are associated with CF-related intestinal dysbiosis. METHODS: An
      in-depth description of CF-associated gut dysbiosis was obtained by screening
      denaturing gradient gel electrophoresis (DGGE) fingerprints for potentially
      discriminating bacterial species, and quantification by means of real-time PCR
      analyses using group-specific primers. RESULTS: A total of 8 DGGE band-classes
      assigned to the genus Bifidobacterium (n=3), and members of Clostridium clusters
      XIVa (n=3) and IV (n=2), were significantly (p<0.05) underrepresented in samples
      of patients with CF. Real-time PCR analyses confirmed a significantly lower
      abundance and temporal stability of bifidobacteria and Clostridium cluster XIVa
      in the fecal microbiota of patients with CF. CONCLUSION: This study is the first
      to report specific microbial determinants of dysbiosis in patients with CF.

PMID- 23151541
TI  - Be persuasive. Be brave. Be arrested (if necessary).

PMID- 23151554
TI  - Snow survey hopes for avalanche of data.

PMID- 23151553
TI  - Obama reasserts research focus.

PMID- 23151555
TI  - Chelation-therapy heart trial draws fire.

PMID- 23151556
TI  - Pig geneticists go the whole hog.

PMID- 23151557
TI  - Investment relief for biotech sector.

PMID- 23151558
TI  - Berlin aims to create research powerhouse.

PMID- 23151559
TI  - Reproductive biology: Fertile mind.

PMID- 23151560
TI  - Simulation: Quantum leaps.

PMID- 23151561
TI  - Computing: secure the internet.

PMID- 23151567
TI  - Human behaviour: environmental stress seen since antiquity.

PMID- 23151562
TI  - Biotechnology: Bring more rigour to GM research.

PMID- 23151568
TI  - Lab animals: Standardize the diet for zebrafish model.

PMID- 23151569
TI  - University of California: union improves postdocs' rights.

PMID- 23151570
TI  - Energy: Clean stoves already in use in rural India.

PMID- 23151571
TI  - Collaboration: Biomedical network in South America.

PMID- 23151572
TI  - Edward Donnall Thomas (1920-2012).

PMID- 23151573
TI  - Climate science: Historical drought trends revisited.

PMID- 23151574
TI  - Animal behaviour: Personality in the wild.

PMID- 23151575
TI  - Quantum physics: Putting a spin on photon entanglement.

PMID- 23151576
TI  - Metabolism and disease.

PMID- 23151577
TI  - Circadian topology of metabolism.
AB  - Biological clocks are genetically encoded oscillators that allow organisms to
      anticipate changes in the light-dark environment that are tied to the rotation of
      Earth. Clocks enhance fitness and growth in prokaryotes, and they are expressed
      throughout the central nervous system and peripheral tissues of multicelled
      organisms in which they influence sleep, arousal, feeding and metabolism.
      Biological clocks capture the imagination because of their tie to geophysical
      time, and tools are now in hand to analyse their function in health and disease
      at the cellular and molecular level.

PMID- 23151578
TI  - Central nervous system control of metabolism.
AB  - Although it is a widely held thought that direct hormone action on peripheral
      tissues is sufficient to mediate the control of nutrient handling, the role of
      the central nervous system in certain aspects of metabolism has long been
      recognized. Furthermore, recent findings have suggested a more general role for
      the central nervous system in metabolic control, and have revealed the importance
      of a number of cues and hypothalamic circuits. The brain's contributions to
      metabolic control are more readily revealed and play a crucial part in catabolic
      states or in hormone deficiencies that mimic starvation.

PMID- 23151579
TI  - How cancer metabolism is tuned for proliferation and vulnerable to disruption.
AB  - Cancer metabolism has received a substantial amount of interest over the past
      decade. The advances in analytical tools have, along with the rapid progress of
      cancer genomics, generated an increasingly complex understanding of metabolic
      reprogramming in cancer. As numerous connections between oncogenic signalling
      pathways and metabolic activities emerge, the importance of metabolic
      reprogramming in cancer is being increasingly recognized. The identification of
      metabolic weaknesses of cancer cells has been used to create strategies for
      treating cancer, but there are still challenges to be faced in bringing the drugs
      that target cancer metabolism to the clinic.

PMID- 23151580
TI  - Mitochondrial disorders as windows into an ancient organelle.
AB  - Much of our current knowledge about mitochondria has come from studying patients
      who have respiratory chain disorders. These disorders comprise a large collection
      of individually rare syndromes, each presenting in a unique and often devastating
      way. In recent years, there has been great progress in defining their genetic
      basis, but we still know little about the cascade of events that gives rise to
      such diverse pathology. Here, we review these disorders and explore them in the
      context of a contemporary understanding of mitochondrial evolution, biochemistry
      and genetics. Fully deciphering their pathogenesis is a challenging next step
      that will inspire the development of drug treatments for rare and common
      diseases.

PMID- 23151581
TI  - Metabolic phenotyping in clinical and surgical environments.
AB  - Metabolic phenotyping involves the comprehensive analysis of biological fluids or
      tissue samples. This analysis allows biochemical classification of a person's
      physiological or pathological states that relate to disease diagnosis or
      prognosis at the individual level and to disease risk factors at the population
      level. These approaches are currently being implemented in hospital environments
      and in regional phenotyping centres worldwide. The ultimate aim of such work is
      to generate information on patient biology using techniques such as patient
      stratification to better inform clinicians on factors that will enhance diagnosis
      or the choice of therapy. There have been many reports of direct applications of
      metabolic phenotyping in a clinical setting.

PMID- 23151584
TI  - A primordial origin for misalignments between stellar spin axes and planetary
      orbits.
AB  - The existence of gaseous giant planets whose orbits lie close to their host stars
      ('hot Jupiters') can largely be accounted for by planetary migration associated
      with viscous evolution of proto-planetary nebulae. Recently, observations of the
      Rossiter-McLaughlin effect during planetary transits have revealed that a
      considerable fraction of hot Jupiters are on orbits that are misaligned with
      respect to the spin axes of their host stars. This observation has cast doubt on
      the importance of disk-driven migration as a mechanism for producing hot
      Jupiters. Here I show that misaligned orbits can be a natural consequence of disk
      migration in binary systems whose orbital plane is uncorrelated with the spin
      axes of the individual stars. The gravitational torques arising from the
      dynamical evolution of idealized proto-planetary disks under perturbations from
      massive distant bodies act to misalign the orbital planes of the disks relative
      to the spin poles of their host stars. As a result, I suggest that in the absence
      of strong coupling between the angular momentum of the disk and that of the host
      star, or of sufficient dissipation that acts to realign the stellar spin axis and
      the planetary orbits, the fraction of planetary systems (including systems of
      'hot Neptunes' and 'super-Earths') whose angular momentum vectors are misaligned
      with respect to their host stars will be commensurate with the rate of primordial
      stellar multiplicity.

PMID- 23151583
TI  - Broad and potent neutralization of HIV-1 by a gp41-specific human antibody.
AB  - Characterization of human monoclonal antibodies is providing considerable insight
      into mechanisms of broad HIV-1 neutralization. Here we report an HIV-1 gp41
      membrane-proximal external region (MPER)-specific antibody, named 10E8, which
      neutralizes ~98% of tested viruses. An analysis of sera from 78 healthy HIV-1
      infected donors demonstrated that 27% contained MPER-specific antibodies and 8%
      contained 10E8-like specificities. In contrast to other neutralizing MPER
      antibodies, 10E8 did not bind phospholipids, was not autoreactive, and bound cell
      surface envelope. The structure of 10E8 in complex with the complete MPER
      revealed a site of vulnerability comprising a narrow stretch of highly conserved
      gp41-hydrophobic residues and a critical arginine or lysine just before the
      transmembrane region. Analysis of resistant HIV-1 variants confirmed the
      importance of these residues for neutralization. The highly conserved MPER is a
      target of potent, non-self-reactive neutralizing antibodies, suggesting that HIV
      1 vaccines should aim to induce antibodies to this region of HIV-1 envelope
      glycoprotein.

PMID- 23151585
TI  - Quantum-dot spin-photon entanglement via frequency downconversion to telecom
      wavelength.
AB  - Long-distance quantum teleportation and quantum repeater technologies require
      entanglement between a single matter quantum bit (qubit) and a telecommunications
      (telecom)-wavelength photonic qubit. Electron spins in III-V semiconductor
      quantum dots are among the matter qubits that allow for the fastest spin
      manipulation and photon emission, but entanglement between a single quantum-dot
      spin qubit and a flying (propagating) photonic qubit has yet to be demonstrated.
      Moreover, many quantum dots emit single photons at visible to near-infrared
      wavelengths, where silica fibre losses are so high that long-distance quantum
      communication protocols become difficult to implement. Here we demonstrate
      entanglement between an InAs quantum-dot electron spin qubit and a photonic
      qubit, by frequency downconversion of a spontaneously emitted photon from a
      singly charged quantum dot to a wavelength of 1,560 nanometres. The use of sub-10
      picosecond pulses at a wavelength of 2.2 micrometres in the frequency
      downconversion process provides the necessary quantum erasure to eliminate which
      path information in the photon energy. Together with previously demonstrated
      indistinguishable single-photon emission at high repetition rates, the present
      technique advances the III-V semiconductor quantum-dot spin system as a promising
      platform for long-distance quantum communication.

PMID- 23151586
TI  - Observation of entanglement between a quantum dot spin and a single photon.
AB  - Entanglement has a central role in fundamental tests of quantum mechanics as well
      as in the burgeoning field of quantum information processing. Particularly in the
      context of quantum networks and communication, a main challenge is the efficient
      generation of entanglement between stationary (spin) and propagating (photon)
      quantum bits. Here we report the observation of quantum entanglement between a
      semiconductor quantum dot spin and the colour of a propagating optical photon.
      The demonstration of entanglement relies on the use of fast, single-photon
      detection, which allows us to project the photon into a superposition of red and
      blue frequency components. Our results extend the previous demonstrations of
      single-spin/single-photon entanglement in trapped ions, neutral atoms and
      nitrogen-vacancy centres to the domain of artificial atoms in semiconductor
      nanostructures that allow for on-chip integration of electronic and photonic
      elements. As a result of its fast optical transitions and favourable selection
      rules, the scheme we implement could in principle generate nearly deterministic
      entangled spin-photon pairs at a rate determined ultimately by the high
      spontaneous emission rate. Our observation constitutes a first step towards
      implementation of a quantum network with nodes consisting of semiconductor spin
      quantum bits.

PMID- 23151587
TI  - Little change in global drought over the past 60 years.
AB  - Drought is expected to increase in frequency and severity in the future as a
      result of climate change, mainly as a consequence of decreases in regional
      precipitation but also because of increasing evaporation driven by global
      warming. Previous assessments of historic changes in drought over the late
      twentieth and early twenty-first centuries indicate that this may already be
      happening globally. In particular, calculations of the Palmer Drought Severity
      Index (PDSI) show a decrease in moisture globally since the 1970s with a
      commensurate increase in the area in drought that is attributed, in part, to
      global warming. The simplicity of the PDSI, which is calculated from a simple
      water-balance model forced by monthly precipitation and temperature data, makes
      it an attractive tool in large-scale drought assessments, but may give biased
      results in the context of climate change. Here we show that the previously
      reported increase in global drought is overestimated because the PDSI uses a
      simplified model of potential evaporation that responds only to changes in
      temperature and thus responds incorrectly to global warming in recent decades.
      More realistic calculations, based on the underlying physical principles that
      take into account changes in available energy, humidity and wind speed, suggest
      that there has been little change in drought over the past 60 years. The results
      have implications for how we interpret the impact of global warming on the
      hydrological cycle and its extremes, and may help to explain why palaeoclimate
      drought reconstructions based on tree-ring data diverge from the PDSI-based
      drought record in recent years.

PMID- 23151588
TI  - Slowdown of the Walker circulation driven by tropical Indo-Pacific warming.
AB  - Global mean sea surface temperature (SST) has risen steadily over the past
      century, but the overall pattern contains extensive and often uncertain spatial
      variations, with potentially important effects on regional precipitation.
      Observations suggest a slowdown of the zonal atmospheric overturning circulation
      above the tropical Pacific Ocean (the Walker circulation) over the twentieth
      century. Although this change has been attributed to a muted hydrological cycle
      forced by global warming, the effect of SST warming patterns has not been
      explored and quantified. Here we perform experiments using an atmospheric model,
      and find that SST warming patterns are the main cause of the weakened Walker
      circulation over the past six decades (1950-2009). The SST trend reconstructed
      from bucket-sampled SST and night-time marine surface air temperature features a
      reduced zonal gradient in the tropical Indo-Pacific Ocean, a change consistent
      with subsurface temperature observations. Model experiments with this trend
      pattern robustly simulate the observed changes, including the Walker circulation
      slowdown and the eastward shift of atmospheric convection from the Indonesian
      maritime continent to the central tropical Pacific. Our results cannot establish
      whether the observed changes are due to natural variability or anthropogenic
      global warming, but they do show that the observed slowdown in the Walker
      circulation is presumably driven by oceanic rather than atmospheric processes.

PMID- 23151590
TI  - Variation in receipt of radiation therapy after breast-conserving surgery:
      assessing the impact of physicians and geographic regions.
AB  - BACKGROUND: Among older women with early-stage breast cancer, patients with a
      short life expectancy (LE) are much less likely to benefit from adjuvant
      radiation therapy (RT). Little is known about the impact of physicians and
      regional factors on the use of RT across LE groups. OBJECTIVE: To determine the
      relative contribution of patient, physician, and regional factors on the use of
      RT. DESIGN: Retrospective cohort. SUBJECTS: Women aged 67-94 years diagnosed with
      stage I breast cancer between 1998 and 2007 receiving breast-conserving surgery.
      MEASURES: We evaluated patient, physician, and regional factors for their
      association with RT across strata of LE using a 3-level hierarchical logistic
      regression model. Risk-standardized treatment rates (RSTRs) for the receipt of
      radiation were calculated according to primary surgeon and region. RESULTS:
      Approximately 43.6% of the 2253 women with a short LE received RT, compared with
      90.8% of the 11,027 women with a long LE. Among women with a short LE, the
      probability of receiving RT varied substantially across primary surgeons; RSTRs
      ranged from 27.7% to 67.3% (mean, 43.9%). There was less variability across
      geographic regions; RSTRs ranged from 42.0% to 45.2% (mean, 43.6%). Short LE
      patients were more likely to receive RT in areas with high radiation oncologist
      density (odds ratio, 1.59; 95% confidence interval, 1.07-2.36). CONCLUSIONS:
      Although there is a wide variation across geographic regions in the use of RT
      among women with breast cancer and short LE, the regional variation was
      substantially diminished after accounting for the operating surgeon.

PMID- 23151592
TI  - Unilateral mastitis obliterans presented as a palpable breast mass in a patient
      with long-standing diabetes mellitus.
AB  - Mastitis obliterans is an uncommon and late manifestation of ductal ectasia. We
      report a case of a woman with a long-term type 2 diabetes, referred to us because
      of a palpable right breast mass. Mammography showed an asymmetry in the palpated
      area. Ultrasonography was consistent with a an irregular, hypoechoic mass with
      indistinct margins and linear tracts to the skin. The biopsy showed a fibrotic
      component surrounding dilated galactophore ducts, which were collapsed by an
      infiltrate of lymphocytes and histiocytes corresponding to mastitis obliterans.
      The differential diagnosis should be made between diabetic fibrous mastopathy,
      granulomatous mastitis and lobular carcinoma. In our opinion, the therapeutic
      approach should depend on the symptomatology and should be individualized for
      each patient owing to the lack of information on this pathology, adopting
      therefore a conservative attitude.

PMID- 23151591
TI  - Hospital nursing and 30-day readmissions among Medicare patients with heart
      failure, acute myocardial infarction, and pneumonia.
AB  - BACKGROUND: Provisions of the Affordable Care Act that increase hospitals'
      financial accountability for preventable readmissions have heightened interest in
      identifying system-level interventions to reduce readmissions. OBJECTIVES: To
      determine the relationship between hospital nursing; that is, nurse work
      environment, nurse staffing levels, and nurse education, and 30-day readmissions
      among Medicare patients with heart failure, acute myocardial infarction, and
      pneumonia. METHOD AND DESIGN: Analysis of linked data from California, New
      Jersey, and Pennsylvania that included information on the organization of
      hospital nursing (ie, work environment, patient-to-nurse ratios, and proportion
      of nurses holding a BSN degree) from a survey of nurses, as well as patient
      discharge data, and American Hospital Association Annual Survey data. Robust
      logistic regression was used to estimate the relationship between nursing factors
      and 30-day readmission. RESULTS: Nearly 1 quarter of heart failure index
      admissions [23.3% (n=39,954)], 19.1% (n=12,131) of myocardial infarction
      admissions, and 17.8% (n=25,169) of pneumonia admissions were readmitted within
      30 days. Each additional patient per nurse in the average nurse's workload was
      associated with a 7% higher odds of readmission for heart failure [odds ratio
      (OR)=1.07; confidence interval CI, 1.05-1.09], 6% for pneumonia patients
      (OR=1.06; CI, 1.03-1.09), and 9% for myocardial infarction patients (OR=1.09; CI,
      1.05-1.13). Care in a hospital with a good versus poor work environment was
      associated with odds of readmission that were 7% lower for heart failure
      (OR=0.93; CI, 0.89-0.97), 6% lower for myocardial infarction (OR=0.94; CI, 0.88
      0.98), and 10% lower for pneumonia (OR=0.90; CI, 0.85-0.96) patients.
      CONCLUSIONS: Improving nurses' work environments and staffing may be effective
      interventions for preventing readmissions.

PMID- 23151582
TI  - Analyses of pig genomes provide insight into porcine demography and evolution.
AB  - For 10,000 years pigs and humans have shared a close and complex relationship.
      From domestication to modern breeding practices, humans have shaped the genomes
      of domestic pigs. Here we present the assembly and analysis of the genome
      sequence of a female domestic Duroc pig (Sus scrofa) and a comparison with the
      genomes of wild and domestic pigs from Europe and Asia. Wild pigs emerged in
      South East Asia and subsequently spread across Eurasia. Our results reveal a deep
      phylogenetic split between European and Asian wild boars ~1 million years ago,
      and a selective sweep analysis indicates selection on genes involved in RNA
      processing and regulation. Genes associated with immune response and olfaction
      exhibit fast evolution. Pigs have the largest repertoire of functional olfactory
      receptor genes, reflecting the importance of smell in this scavenging animal. The
      pig genome sequence provides an important resource for further improvements of
      this important livestock species, and our identification of many putative disease
      causing variants extends the potential of the pig as a biomedical model.

PMID- 23151594
TI  - Emotional intimacy is the best predictor of sexual satisfaction of men and women
      with sexual arousal problems.
AB  - This study investigates the association between variables related to individual
      body appearance and relationship variables with sexual satisfaction (SS) in a
      sample of men and women with sexual arousal problems (SAP). An anonymous cross
      sectional survey was conducted in a clinical setting with a non-representative
      sample of people diagnosed (DSP) with SAP and with a sample of people who
      identified themselves (SISP) as having a SAP. A total of 193 participants was
      recruited. SS and variables related to body appearance and relationship were
      measured. Hierarchical regression was used to study the contribution of different
      sets of variables on SS of men and women. No differences were found in terms of
      demographic variables, except for gender. Women in the SISP group presented
      significantly higher levels of SS than women in the DSP group. The predictive
      models proved to be statistically significant and explained many of the variance
      of SS in both men (R(2)=0.44) and women (R(2)=0.40). In both genders, emotional
      intimacy was revealed to be the main predictor of SS. Our results support the
      need to address relationship variables in patients diagnosed with SAP,
      specifically intimacy. This latter component must be considered for assessment,
      intervention and referral.

PMID- 23151593
TI  - Loss of pigment epithelium-derived factor: a novel mechanism for the development
      of endocrine resistance in breast cancer.
AB  - INTRODUCTION: Despite the benefits of endocrine therapies such as tamoxifen and
      aromatase inhibitors in treating estrogen receptor (ER) alpha-positive breast
      cancer, many tumors eventually become resistant. The molecular mechanisms
      governing resistance remain largely unknown. Pigment epithelium-derived factor
      (PEDF) is a multifunctional secreted glycoprotein that displays broad anti-tumor
      activity based on dual targeting of the tumor microenvironment (anti-angiogenic
      action) and the tumor cells (direct anti-tumor action). Recent studies indicate
      that PEDF expression is significantly reduced in several tumor types, including
      breast cancer, and that its reduction is associated with disease progression and
      poor patient outcome. In the current study, we investigated the role of PEDF in
      the development of endocrine resistance in breast cancer. METHODS: PEDF mRNA and
      protein levels were measured in several endocrine-resistant breast cancer cell
      lines including MCF-7:5C, MCF-7:2A, and BT474 and in endocrine-sensitive cell
      lines MCF-7, T47D, and ZR-75-1 using real-time PCR and western blot analyses.
      Tissue microarray analysis and immunohistochemistry were used to assess the PEDF
      protein level in tamoxifen-resistant breast tumors versus primary tumors.
      Lentiviruses were used to stably express PEDF in endocrine-resistant breast
      cancer cell lines to determine their sensitivity to tamoxifen following PEDF re
      expression. RESULTS: We found that PEDF mRNA and protein levels were dramatically
      reduced in endocrine-resistant MCF-7:5C, MCF-7:2A, and BT474 breast cancer cells
      compared with endocrine-sensitive MCF-7, T47D, and ZR-75-1 cells, and that loss
      of PEDF was associated with enhanced expression of pSer167ERalpha and the
      receptor tyrosine kinase rearranged during transfection (RET). Importantly, we
      found that silencing endogenous PEDF in tamoxifen-sensitive MCF-7 and T47D breast
      cancer cells conferred tamoxifen resistance whereas re-expression of PEDF in
      endocrine-resistant MCF-7:5C and MCF-7:2A cells restored their sensitivity to
      tamoxifen in vitro and in vivo through suppression of RET. Lastly, tissue
      microarray studies revealed that PEDF protein was reduced in ~52.4% of recurrence
      tumors (31 out of 59 samples) and loss of PEDF was associated with disease
      progression and poor patient outcome. CONCLUSION: Overall, these findings suggest
      that PEDF silencing might be a novel mechanism for the development of endocrine
      resistance in breast cancer and that PEDF expression might be a predictive marker
      of endocrine sensitivity.

PMID- 23151595
TI  - Hospital and nursing home use from 2002 to 2008 among U.S. older adults with
      cognitive impairment, not dementia in 2002.
AB  - Little is known about health care use in the cognitive impairment, not dementia
      (CIND) subpopulation. Using a cohort of 7130 persons aged 71 years or over from
      the Health and Retirement Survey, we compared mean and total health care use from
      2002 to 2008 for those with no cognitive impairment, CIND, or dementia in 2002.
      Cognitive status was determined using a validated method based on self or proxy
      interview measures. Health care use was also based on self or proxy reports. On
      the basis of the Health and Retirement Survey, the CIND subpopulation in 2002 was
      5.3 million or 23% of the total population 71 years of age or over. Mean hospital
      nights was similar and mean nursing home nights was less in persons with CIND
      compared with persons with dementia. The CIND subpopulation, however, had more
      total hospital and nursing home nights--71,000 total hospital nights and 223,000
      total nursing home nights versus 32,000 hospital nights and 138,000 nursing home
      nights in the dementia subpopulation. A relatively large population and high
      health care use result in a large health care impact of the CIND subpopulation.

PMID- 23151597
TI  - Association between the +104T/C polymorphism in the 5'UTR of GDF5 and
      susceptibility to knee osteoarthritis: a meta-analysis.
AB  - Although the +104T/C polymorphism in the 5' untranslated region (UTR) of growth
      differentiation factor 5 (GDF5) plays a role in the pathogenesis of knee
      osteoarthritis, the results have been inconsistent. In this study, we performed a
      meta-analysis to assess the association of +104T/C polymorphism with knee
      osteoarthritis. Published literature from PubMed, Google Scholar and China
      National Knowledge Infrastructure data was retrieved. Pooled odds ratios (ORs)
      with 95% confidence intervals (CIs) were calculated using fixed- or random
      effects models. A total of 6 case-control studies containing 2,744 patients and
      4,518 controls were enrolled in this meta-analysis. Overall, a statistically
      significant association was found between the +104T/C polymorphism and risk of
      knee osteoarthritis (TT vs. CC: OR 1.68, 95% CI=1.41-2.01; TT vs. TC: OR 1.18,
      95% CI=1.01-1.38; dominant model: OR 0.72, 95% CI=0.61-0.86). Taking into account
      the effect of ethnicity, further stratified analyses were performed. In the
      subgroup analysis, the same association was identified in Caucasian (TT vs. CC:
      OR 1.45, 95% CI=1.13-1.85) and Asian (TT vs. CC: OR 1.99, 95% CI=1.53-2.60; TT
      vs. TC: OR 1.33, 95% CI=1.16-1.52; dominant model: OR 0.64, 95% CI=0.56-0.72;
      recessive model: OR 1.77, 95% CI=1.37-2.29) populations. The meta-analysis
      results demonstrated that the +104T/C polymorphism in the 5'-UTR of GDF5 is
      associated with risk of knee osteoarthritis.

PMID- 23151596
TI  - Developing dementia prevention trials: baseline report of the Home-Based
      Assessment study.
AB  - This report describes the baseline experience of the multicenter, Home-Based
      Assessment study, designed to develop methods for dementia prevention trials
      using novel technologies for test administration and data collection. Nondemented
      individuals of 75 years of age or more were recruited and evaluated in-person
      using established clinical trial outcomes of cognition and function, and
      randomized to one of 3 assessment methodologies: (1) mail-in questionnaire/live
      telephone interviews [mail-in/phone (MIP)]; (2) automated telephone with
      interactive voice recognition; and (3) internet-based computer Kiosk. Brief
      versions of cognitive and noncognitive outcomes were adapted to each methodology
      and administered at baseline and repeatedly over a 4-year period. "Efficiency"
      measures assessed the time from screening to baseline, and staff time required
      for each methodology. A total of 713 individuals signed consent and were
      screened; 640 met eligibility and were randomized to one of 3 assessment arms;
      and 581 completed baseline. Dropout, time from screening to baseline, and total
      staff time were highest among those assigned to internet-based computer Kiosk.
      However, efficiency measures were driven by nonrecurring start-up activities
      suggesting that differences may be mitigated over a long trial. Performance among
      Home-Based Assessment instruments collected through different technologies will
      be compared with established outcomes over this 4-year study. 

PMID- 23151598
TI  - Usefulness of the combined application of the Mood Disorder Questionnaire and
      Bipolar Spectrum Diagnostic Scale in screening for bipolar disorder.
AB  - OBJECTIVE: This study aimed to examine whether combined application of the Mood
      Disorder Questionnaire (MDQ) and Bipolar Spectrum Diagnostic Scale (BSDS) is more
      effective than exclusive application of either tool in screening for bipolar
      disorder (BD). METHOD: The MDQ and BSDS were completed by a total of 113 patients
      diagnosed with BD and major depressive disorder who were experiencing a current
      major depressive episode. The initial diagnosis of the subject was confirmed
      during a 1-year follow-up period. When each MDQ and BSDS optimal cutoff score was
      calculated, a modified scoring method for the MDQ that considered only one item
      was used to increase its performance in this population. The following three
      combinations of the cutoff scores for the two tools were used to screen for BD:
      (A) The score on either the MDQ or BSDS was greater than or equal to the cutoff
      score; (B) the scores on both the MDQ and BSDS were greater than or equal to the
      cutoff score; and (C) Reducing either cutoff score by 1 point resulted in the MDQ
      and BSDS scores being greater than or equal to the cutoff score. The sensitivity,
      specificity, positive predictive value, and negative predictive value of the
      three methods, the MDQ, and the BSDS were compared for screening BD. RESULTS: The
      sensitivity and specificity of the MDQ were 0.741 and 0.844, respectively, and
      those for the BSDS were 0.731 and 0.742, respectively. These indicators for the
      combined application of the MDQ and BSDS were as follows, respectively: method A
      0.901 and 0.688, method B 0.580 and 0.875, and method C 0.691 and 0.844. Method A
      was superior to using one measure alone as well as to methods B and C with regard
      to sensitivity and negative predictive values. Method A also showed a higher
      sensitivity for BD subtypes than did the individual tools. Compared with the use
      of individual instruments, method A showed a similar positive predictive value.
      CONCLUSION: This study suggests that combined use of the MDQ and BSDS is more
      effective than the individual use of either of these measures in screening for
      BD. The data also showed that when both tools were used, the most effective
      interpretation of the results in terms of screening for BD was achieved when
      positive scores were defined as those that were equal to or greater than the
      cutoff for the MDQ or BSDS.

PMID- 23151599
TI  - The novel focal adhesion gene kindlin-2 promotes the invasion of gastric cancer
      cells mediated by tumor-associated macrophages.
AB  - Kindlin-2 is a novel focal adhesion gene mediating the cell-extracellular matrix
      (ECM) adhesion. Tumor-associated macrophages (TAMs) play an important role in
      linking chronic inflammation to cancer progression. Both kindlin-2 and TAMs have
      been found to promote the invasion of gastric cancer cells in our previous
      studies. However, the correlation between kindlin-2 and TAMs remains unclear.
      Real-time RT-PCR was used to investigate kindlin-2 expression in the AGS, NCI and
      Hs-746T gastric cancer cell lines co-cultured with TAMs under normal or hypoxic
      conditions. IL8, IL10, IL11, IL17b, IL18, IL22 and IL24 expressions were measured
      by real-time RT-PCR in the gastric cancer lines with varying levels of kindlin-2
      expression, as well as after downregulation of kindlin-2 mRNA expression by the
      siRNA method. We found that kindlin-2 was upregulated in all three gastric cancer
      cell lines when co-cultured with TAMs under normal conditions. Under hypoxic
      conditions, the induction of kindlin-2 expression induced by macrophages was
      significantly downregulated in the Hs-746T cell line. IL8, IL11, IL17b, IL22 and
      IL24 expression was significantly higher in gastric cell lines with high kindlin
      2 expression. Downregulation of kindlin-2 mRNA decreased IL10, IL11, IL17b, IL22
      and IL24 expression but IL8 and IL18 expression was upregulated. Therefore, the
      novel focal adhesion gene kindlin-2 may play an important role in promoting the
      invasion of gastric cancer cells mediated by TAMs through regulating interleukin
      expression.

PMID- 23151600
TI  - Growth inhibition and apoptosis-inducing effect on human cancer cells by RCE-4, a
      spirostanol saponin derivative from natural medicines.
AB  - Reineckia carnea has been used to treat several diseases in folk remedies. RCE-4
      has been isolated from several plants of the family Liliaceae, but its biological
      activity has not yet been reported. In the present study, we found that RCE-4
      exhibited potent cytotoxicity to the tested human cancer cell lines, and the
      CaSki cell line was the most sensitive with an IC50 of 3.37 uM. Thus, we
      presented the apoptosis-inducing effect of RCE-4 on CaSki cervical cancer cells
      and investigated the relevant mechanisms. Based on observations using
      transmission electron microscopy, RCE-4-treated cells manifested nuclear
      shrinkage, condensation and fragmentation. Annexin V/PI dual staining flow
      cytometry assay further confirmed that RCE-4 caused a dose-dependent early
      apoptotic effect. Prior to these events, RCE-4 triggered a rapid decrease of the
      mitochondrial membrane potential and caused the release of cytochrome c from the
      mitochondria into the cytoplasm. RCE-4 increased the expression of Bax and
      decreased the expression of Bcl-2, thus augmenting the Bax/Bcl-2 ratio. These
      findings suggest that RCE-4 induces mitochondrial-mediated apoptosis in CaSki
      cells and has the potential to be developed as an anticancer agent.

PMID- 23151601
TI  - Leukaemia: Early changes.

PMID- 23151602
TI  - Lymphoma: Epigenetic therapy gains momentum.

PMID- 23151604
TI  - Metabolism: Warburg behind the butyrate paradox?

PMID- 23151603
TI  - Future directions in cancer prevention.
AB  - Prevention of cancer remains the most promising strategy for reducing both its
      incidence and the mortality due to this disease. For more than four decades,
      findings from epidemiology, basic research and clinical trials have informed the
      development of lifestyle and medical approaches to cancer prevention. These
      include selective oestrogen receptor modulators and aromatase inhibitors for
      breast cancer, the 5-alpha-reductase inhibitors finasteride and dutasteride for
      prostate cancer, and the development of vaccines for viruses that are associated
      with specific cancers. Future directions include genetic, proteomic and other
      molecular approaches for identifying pathways that are associated with cancer
      initiation and development, as well as refining the search for immunologically
      modifiable causes of cancer.

PMID- 23151606
TI  - Protein co-evolution: how do we combine bioinformatics and experimental
      approaches?
AB  - Molecular co-evolution is manifested by compensatory changes in proteins designed
      to enable adaptation to their natural environment. In recent years,
      bioinformatics approaches allowed for the detection of co-evolution at the level
      of the whole protein or of specific residues. Such efforts enabled prediction of
      protein-protein interactions, functional assignments of proteins and the
      identification of interacting residues, thereby providing information on protein
      structure. Still, despite such advances, relatively little is known regarding the
      functional implications of sequence divergence resulting from protein co
      evolution. While bioinformatics approaches usually analyze thousands of proteins
      to obtain a broad view of protein co-evolution, experimental evaluation of
      protein co-evolution serves to study only individual proteins. In this review, we
      describe recent advances in bioinformatics and experimental efforts aimed at
      examining protein co-evolution. Accordingly, we discuss possible modes of
      crosstalk between the bioinformatics and experimental approaches to facilitate
      the identification of co-evolutionary signals in proteins and to understand their
      implications for the structure and function of proteins.

PMID- 23151608
TI  - Free and pedicled appendix transfer for various reconstructive procedures.
AB  - INTRODUCTION: The appendix has a constant vascular anatomy and provides a small
      lumen that always maintains its patency because of mucosal secretion and
      motility; thus, it serves as an ideal conduit structurally. The appendix has been
      used in urologic surgeries as a pedicled flap and as a free flap in isolated case
      reports for the reconstruction of the urethra. However, this study proposes more
      extended applications of the appendix in different kinds of reconstruction.
      METHODS: From 2002 to 2011, 11 patients were included in this study
      retrospectively. Of these cases, 8 were transferred as free flaps, whereas the
      other 3 were pedicle flaps. Among the 8 free appendix transfers (A and B), 5 of
      them were used for voice reconstruction by creating a tracheoesophageal fistula;
      the other 3 were transferred to reconstruct the male urethra. Among the 3
      pedicled appendix transfer, 2 were used for reconstruction of cervix and vagina,
      whereas the other was used for reconstruction of esophagus and voice tube
      simultaneously after ablation of cancers in the hypopharynx and esophagus.
      RESULTS: All cases showed successful results not only structurally but also
      functionally. As for voice reconstruction, the appendix serves as an autologous
      fistula between the trachea and the esophagus with minimal complications and no
      aspirations. The intelligibility and loudness were fair to excellent, whereas
      fluency required persistent training and practice.For patients who underwent
      urethral reconstruction, their micturition was smooth with ease postoperatively.
      Two of the patients also received penile reconstruction with fibula
      osteocutaneous flap simultaneously during the urethral reconstruction.As for
      reconstruction of cervix and vagina, pedicled appendix-cecum-colon-complex is a
      great option offering long-term patency with an expandable diameter up to 2.5 cm.
      CONCLUSIONS: Appendix has a reliable vascularity and a unique structure for
      reconstruction of conduit-like organs, and combining its adjacent bowel segments,
      including ileum, cecum, and colon, during tissue transfer not only increases its
      length but provides more applications and possibilities for reconstruction of
      different parts of the body. Removal of the appendix carries minimal morbidity.
      Our study proved the applicability and reliability of free and pedicled appendix
      transfer.

PMID- 23151609
TI  - A survey of bio-inspired compliant legged robot designs.
AB  - The roles of biological springs in vertebrate animals and their implementations
      in compliant legged robots offer significant advantages over the rigid legged
      ones in certain types of scenarios. A large number of robotics institutes have
      been attempting to work in conjunction with biologists and incorporated these
      principles into the design of biologically inspired robots. The motivation of
      this review is to investigate the most published compliant legged robots and
      categorize them according to the types of compliant elements adopted in their
      mechanical structures. Based on the typical robots investigated, the trade-off
      between each category is summarized. In addition, the most significant
      performances of these robots are compared quantitatively, and multiple available
      solutions for the future compliant legged robot design are suggested. Finally,
      the design challenges for compliant legged robots are analysed. This review will
      provide useful guidance for robotic designers in creating new designs by
      inheriting the virtues of those successful robots according to the specific
      tasks.

PMID- 23151610
TI  - One hundred years of helicene chemistry. Part 2: stereoselective syntheses and
      chiral separations of carbohelicenes.
AB  - Carbohelicenes generally incorporate a helical, distorted, conjugated,
      polyaromatic system with ortho-fused benzenoid rings, which is a fundamental
      molecular characteristic of this class of compounds. They have been described as
      "molecules in distress" due to their distortion. The generation of a chiral
      helicity in helicenes was observed because of a severe intramolecular steric
      strain. Helicity is a molecular necessity in the higher series of carbohelicenes,
      when at some point, a helical pitch occurs when a second coil is formed. The most
      interesting properties resulting from such molecular distortion are the very high
      chiroptical and circular dichroism values. For instance, the resolution of some
      helicene racemates by "hand picking" of a few homochiral single enantiomeric
      crystals allowed for a measurement of their optical rotation. Due to that
      intrinsic chirality spanned over a large polyaromatic template, preliminary
      results clearly established the efficiency of carbohelicenes to induce asymmetry
      and chirality in organic synthesis and in supramolecular chemistry. Additionally,
      they have some potential uses in several fields: materials science, nanoscience,
      chemical biology and supramolecular chemistry. It has encouraged many attempts to
      develop new asymmetric syntheses of carbohelicenes, as well as some chiral
      separations of enantiomers and diastereoisomers. This review is thus dedicated to
      carbohelicene chirality. It gathered a substantial collection of data, and a
      comprehensive review on the preparations of enantioenriched helicenes, either
      from an asymmetric synthesis or from a chiral separation. Utilizations of non
      racemic helicenes and their applications will be treated in the following review
      (Part 3), and will not be the subject of this manuscript.

PMID- 23151607
TI  - Efficient synthesis of RITA and its analogues: derivation of analogues with
      improved antiproliferative activity via modulation of p53/miR-34a pathway.
AB  - A novel approach to synthesize RITA by practical palladium-catalyzed C-C bond
      forming Suzuki reactions at room temperature was developed, which was used for
      deriving a series of substituted tricyclic alpha-heteroaryl (furan/thiophene)
      analogues of RITA under mild conditions. These novel analogues showed notable
      antiproliferative activity against cancer cell lines with wild-type p53 (i.e.,
      HCT116, A549, MCF-7 and K562), but much less activity in HCT116/p53(-/-) cells.
      In particular, compound 1f demonstrated promising antiproliferative activity
      compared to RITA, with IC(50) = 28 nM in MCF-7 vs. 54 nM for RITA, and cancer
      cell selectivity. Compound 1f markedly activated p53 in HCT116 cells at 100 nM,
      triggering apoptosis. Importantly, we found that both RITA and compound 1f
      induced G(0)/G(1) cell cycle arrest by up-regulating miR-34a, which in turn down
      regulated the expression of cell cycle-related proteins CDK4 and E2F1. In
      summary, this study reports an effective synthetic approach for RITA and its
      analogues, and elucidates a novel antiproliferative mechanism of these compounds.

PMID- 23151611
TI  - Antidepressant-like effect of oleanolic acid in mice exposed to the repeated
      forced swimming test.
AB  - The study aimed to explore the antidepressant-like effect of oleanolic acid and
      its possible mechanism related to the monoaminergic system and neurotrophin in
      mice exposed to the repeated forced swimming test (FST). Both the duration and
      the latency of immobility affected by oleanolic acid (10, 20 and 40 mg/kg) were
      evaluated in the FST repeated at intervals on days 1, 7 and 14, followed by
      neurochemical and brain-derived neurotrophic factor (BDNF) analyses in the mouse
      brain regions of frontal cortex and whole hippocampus. A repeated analysis of
      variance (ANOVA) indicated that over retesting the immobility time increased,
      whereas latency to immobility tended to decrease. Minute-by-minute analysis
      showed that immobility time also increased during the 4-min course of the test.
      In addition, post-hoc Dunnett's test demonstrated that sub-chronic and chronic,
      but not acute, oleanolic acid treatment reduced the immobility time (sub-chronic:
      20 mg/kg, 43.5%; chronic: 10 mg/kg, 19.3%; 20 mg/kg, 31.8%) and increased the
      latency to immobility (sub-chronic: 10 mg/kg, 60.6%; 20 mg/kg, 80.1%; chronic: 10
      mg/kg, 121.8%; 20 mg/kg, 140.8%; 40 mg/kg, 80.0%). Furthermore, chronic
      administration of oleanolic acid significantly increased serotonin (5-HT) levels
      (frontal cortex: 44.5%, 41.9%, 27.5% for 10, 20, 40 mg/kg; hippocampus: 57.2%,
      80.9% for 10, 20 mg/kg), decreased 5-hydroxyindoleacetic acid (5-HIAA)/5-HT ratio
      (frontal cortex: 31.6%, 30.1%, 23.5%; hippocampus: 40.6%, 47.7%, 29.2% for 10,
      20, 40 mg/kg) and elevated norepinephrine (NE) levels (hippocampus: 20 mg/kg,
      45.4%) but did not alter dopamine (DA) levels. Moreover, BDNF levels in the two
      brain regions were also elevated by chronic oleanolic acid treatment (frontal
      cortex: 20 mg/kg, 67.2%; hippocampus: 10 mg/kg, 36.4%; 20 mg/kg, 55.1%). Taken
      together, these findings imply that functions of 5-HT, NE and BDNF may be
      involved in the antidepressant-like effect of oleanolic acid.

PMID- 23151605
TI  - Immunogenic cell death and DAMPs in cancer therapy.
AB  - Although it was thought that apoptotic cells, when rapidly phagocytosed,
      underwent a silent death that did not trigger an immune response, in recent years
      a new concept of immunogenic cell death (ICD) has emerged. The immunogenic
      characteristics of ICD are mainly mediated by damage-associated molecular
      patterns (DAMPs), which include surface-exposed calreticulin (CRT), secreted ATP
      and released high mobility group protein B1 (HMGB1). Most DAMPs can be recognized
      by pattern recognition receptors (PRRs). In this Review, we discuss the role of
      endoplasmic reticulum (ER) stress and reactive oxygen species (ROS) in regulating
      the immunogenicity of dying cancer cells and the effect of therapy-resistant
      cancer microevolution on ICD.

PMID- 23151612
TI  - A review of anti-inflammatory agents for symptoms of schizophrenia.
AB  - Schizophrenia is a chronic debilitating mental disorder that affects about 1% of
      the US population. The pathophysiology and etiology remain unknown, thus new
      treatment targets have been challenging and few novel treatments with new
      mechanisms of action have come to market in the past few decades. Increasing
      attention has been paid to the role of inflammation in schizophrenia and new data
      suggests that decreasing inflammation and inflammatory biomarkers may play some
      role in schizophrenia treatment. This review summarizes the clinical trial
      literature regarding medications that possess anti-inflammatory properties that
      have been tested for schizophrenia symptoms and covers such medications as non
      steroidal anti-inflammatory agents, such as the cyclo-oxygenase-2 (COX-2)
      inhibitors and aspirin, omega-3 fatty acids, neurosteroids and minocycline.
      Overall, there is accumulating evidence, albeit mostly adjunctive treatments,
      that agents working on inflammatory pathways have some benefits in people with
      schizophrenia. In the next few years the field will begin to see data on many
      treatments with anti-inflammatory properties that are currently under study.
      Hopefully advancements in understanding inflammation and effective treatments
      having anti-inflammatory properties may help revolutionize our understanding and
      provide new targets for prevention and treatment in schizophrenia.

PMID- 23151614
TI  - Salivary markers of oxidative stress and their relation to periodontal and dental
      status in children.
AB  - BACKGROUND: Previous studies have shown that salivary thiobarbituric acid
      reactive substances are related to the periodontal status in adults. Such an
      analysis has not been done on children yet. The aim of our study was to analyze
      salivary markers of oxidative stress in relation to periodontal and dental status
      in children. METHODS: The periodontal and dental status of 82 consecutive
      pediatric dental patients was assessed. The oral hygiene index (OHI), the
      papillary bleeding index (PBI) and the caries index (CI) were assessed as
      clinical parameters. Markers of oxidative stress and antioxidant status were
      measured in whole saliva samples. RESULTS: Multivariate analysis of covariance
      showed that the variability of PBI explains 10.9% of the variance of salivary
      thiobarbituric acid reacting substances (TBARS). Advanced oxidation protein
      products (AOPP) were related to CI (eta 8.6%). Measures of antioxidant status
      (total antioxidant capacity and ferric reducing ability of saliva) were partially
      determined by OHI (13.6% and 7.2%) and PBI (16.9% and 7.9%). CONCLUSIONS:
      Antioxidant status in saliva is related to oral hygiene and periodontal status.
      Salivary TBARS are a potential sensitive marker of periodontitis in children,
      similarly to adults, at least on a population level. Salivary AOPP are related to
      caries. Potential diagnostic value of the analyzed markers should be analyzed in
      further interventional studies.

PMID- 23151615
TI  - Psoriasin: a novel marker linked obesity with psoriasis.
AB  - To evaluate the role of psoriasin, koebnerisin, interleukn (IL)-12 and IL-23 in
      the pathogenesis of psoriasis and their relations to Psoriasis Area Severity
      Index (PASI) and obesity. Thirty patients had chronic plaque psoriasis and 30
      healthy subjects matched in age and sex were enrolled in this study. Serum from
      all subjects were used for determination of psoriasin, koebnerisin, IL-12 and IL
      23 by ELISA kits. IL-23 and psoriasin were significantly higher in skin psoriasis
      compared to controls and psoriatic arthritis (PsA). There was a correlation
      between psoriasin and both PASI and obesity. On the other hand, IL-12 was
      significantly increased in PsA compared to skin psoriasis (p=0.000) and controls.
      Its sensitivity and specificity were 87%, 93%; respectively. To our knowledge,
      psoriasin is the first biomarker confirm the link between obesity and psoriasis.
      The risk of developing psoriasis is directly related to higher BMI.

PMID- 23151613
TI  - Roles of dopaminergic innervation of nucleus accumbens shell and dorsolateral
      caudate-putamen in cue-induced morphine seeking after prolonged abstinence and
      the underlying D1- and D2-like receptor mechanisms in rats.
AB  - Drug-associated cues can elicit relapse to drug seeking after abstinence. Studies
      with extinction-reinstatement models implicate dopamine (DA) in the nucleus
      accumbens shell (NAshell) and dorsolateral caudate-putamen (dlCPu) in cocaine
      seeking. However, less is known about their roles in cue-induced opiate seeking
      after prolonged abstinence. Using a morphine self-administration and abstinence
      relapse model, we explored the roles of NAshell and dlCPu DA and the D1/D2-like
      receptor mechanisms underlying morphine rewarding and/or seeking. Acquisition of
      morphine self-administration was examined following 6-Hydroxydopamine
      hydrobromide (6-OHDA) lesions of the NAshell and dlCPu. For morphine seeking,
      rats underwent 3 weeks' morphine self-administration followed by 3 weeks'
      abstinence from morphine and the training environment. Prior to testing, 6-OHDA,
      D1 antagonist SCH23390, or D2 antagonist eticlopride was locally injected; then
      rats were exposed to morphine-associated contextual and discrete cues. Results
      show that acquisition of morphine self-administration was inhibited by NAshell
      (not dlCPu) lesions, while morphine seeking was attenuated by lesions of either
      region, by D1 (not D2) receptor blockade in NAshell, or by blockade of either D1
      or D2 receptors in dlCPu. These data indicate a critical role of dopaminergic
      transmission in the NAshell (via D1-like receptors) and dlCPu (via D1- and D2
      like receptors) in morphine seeking after prolonged abstinence.

PMID- 23151616
TI  - Effect of non-surgical periodontal therapy on interleukin-29 levels in gingival
      crevicular fluid of chronic periodontitis and aggressive periodontitis patients.
AB  - Recently discovered interleukin 29 (IL-29) has antiviral properties and its
      production is induced by herpes viruses. This study was aimed at analyzing the
      effect of non-surgical periodontal treatment on IL-29 levels in gingival
      crevicular fluid (GCF) of chronic and aggressive periodontitis patients. A total
      of 60 participants were divided into healthy group (group 1; n=20), chronic
      periodontitis group (group 2; n=20), and aggressive periodontitis group (group 3;
      n=20). GCF samples collected from each subject at baseline and 6-8 weeks after
      scaling and root planing were quantified for IL-29 levels using ELISA. The mean
      IL-29 concentration in GCF was found to be highest in group 3 (92.37 pg/MUl). The
      mean IL-29 level in group 1 and group 2 was 36.88 pg/MUl and 69.35 pg/MUl
      respectively. After scaling and root planing, the mean concentration of IL-29 in
      GCF was increased to 85.99 pg/MUl in group 2 and to 114.64 pg/MUl in group 3.
      Results of the present study indicate that antiviral IL-29 level was highest in
      GCF of aggressive periodontitis patients and least in subjects with healthy
      periodontium, while that of chronic periodontitis lying in between. After non
      surgical periodontal therapy, IL-29 levels increased both in chronic and
      aggressive periodontitis patients and deserve further investigation as a
      potential therapeutic agent in treating periodontitis.

PMID- 23151617
TI  - Association between RAS gene polymorphisms (ACE I/D, AGT M235T) and Henoch
      Schonlein purpura in a Turkish population.
AB  - Henoch-Schonlein purpura (HSP) is a small-vessel vasculitis of autoimmune
      hypersensitivity, and renin-angiotensin system (RAS) regulates vascular
      homeostasis and inflammation with activation of cytokine release. Thus, we aimed
      to investigate the association between HSP and ACE I/D and AGT M235T
      polymorphisms. Genotyping was determined by allele specific PCR and PCR-RFLP. We
      obtained a significant difference in genotype distribution (p=0.003) and allele
      frequencies (p<0.001) of ACE I/D polymorphism between patients and controls,
      while no significant association was detected in genotype distribution (p> 0.05)
      and allele frequencies (p> 0.05) of the AGT M235T polymorphism. Risk assessment
      showed significant risk for HSP in the subjects both with the ID + DD genotype
      (p=0.019, OR: 2.288, 95% CI: 1.136-4.609) and D allele (OR: D vs. I: 2.0528, 95%
      CI: 1.3632-3.0912, p=0.001) while no significant risk was obtained for HSP in the
      subjects both with the MT + TT genotype (p=0.312, OR: 1.3905, 95% T vs. M: 1.065,
      95% CI: 0.7326-2.6391) and T allele (OR: patients were stratified by the presence
      of certain systemic complications of HSP, no significant association was detected
      with ACE I/D, and AGT M235T polymorphisms. Our findings suggest that ACE I/D
      polymorphism is significantly associated with HSP susceptibility.

PMID- 23151618
TI  - Aurora A overexpression and pVHL reduced expression are correlated with a bad
      kidney cancer prognosis.
AB  - We investigate the expression and localization of the tumor suppressor protein
      pVHL as well as the oncoprotein Aurora A kinase in kidney cancer. Both Aurora A
      kinase and pVHL protein status were evaluated using immunohistochemistry. The
      Aurora A expression is correlated with the Fuhrman grade and the TNM stage, while
      the pVHL expression is correlated with the capsule rupture and the TNM stage.
      Aurora A kinase expression increases in malignant tissue comparing to the non
      malignant one. And there is a decrease in pVHL expression from the adjacent
      healthy tissues to the tumor's ones. The two kinds of opposite tumor profiles
      display significant distribution difference according to TNM stages. It could be
      proposed that the absence of Aurora A protein associated with a strong expression
      of pVHL in clear cells kidney carcinoma are of good prognosis for the disease.

PMID- 23151619
TI  - The mechanisms of energy crisis in human astrocytes after subarachnoid
      hemorrhage.
AB  - BACKGROUND: Calcium (Ca2+) is a cofactor of multiple cellular processes. The
      mechanisms that lead to elevated cytosolic Ca2+ concentration are unclear.
      OBJECTIVE: To illuminate how bloody cerebrospinal fluid (bCSF) from patients with
      intraventricular hemorrhage causes cell death of cultured human astrocytes.
      METHODS: Cultured astrocytes were incubated with bCSF. In control experiments,
      native CSF was used. Cytosolic Ca2+ concentration was measured by fura-2
      fluorescence. Apoptosis and necrosis were evaluated by staining with Hoechst-3342
      and propidium iodide. RESULTS: Incubation of astrocytes with bCSF provoked a
      steep Ca2+ concentration peak that was followed by a slow Ca2+ rise during the
      observation period of 50 minutes. Necrosis, but not apoptosis, was induced.
      Blockade of ATP-sensitive P2 receptors with suramin inhibited the bCSF-induced
      initial Ca2+ peak and necrosis. Blockade of P1 receptors with 8
      phenyltheophylline or of N-methyl-D-aspartate receptors with D(-)-2-amino-5
      phosphopentanoic acid had no significant effect. Preincubation with xestospongin
      D, a blocker of inositol 1,4,5-trisphosphate receptors, prevented the initial
      Ca2+ rise and reduced the rate of necrosis. Preemptying of the endoplasmic
      reticulum with thapsigargin protected astrocytes from the bCSF-induced Ca2+ peak.
      Inhibition of mitochondrial permeability transition pores opening with
      cyclosporin A reduced the rate of astrocytic necrosis significantly, although it
      did not influence the initial Ca peak. CONCLUSION: bCSF elicits a steep,
      transient Ca rise when administered to human astrocytes by activation of ATP
      sensitive P2 receptors and subsequent inositol 1,4,5-trisphosphate-dependent Ca
      release from endoplasmic reticulum. This massive Ca overload leads to subsequent
      mitochondrial permeability transition pores opening and necrosis of the cells.

PMID- 23151620
TI  - Staggered transverse tripoles with quadripolar lateral anodes using percutaneous
      and surgical leads in spinal cord stimulation.
AB  - BACKGROUND: In spinal cord stimulation for low-back pain, the use of electrode
      arrays with both low-power requirements and selective activation of target dorsal
      column (DC) fibers is desired. The aligned transverse tripolar lead configuration
      offers the best DC selectivity. Electrode alignment of the same configuration
      using 3 parallel percutaneous leads is possible, but compromised by longitudinal
      migration, resulting in loss of DC selectivity. This loss might be repaired by
      using the adjacent anodal contacts on the lateral leads. OBJECTIVE: To
      investigate if stimulation using adjacent anodal contacts on the lateral
      percutaneous leads of a staggered transverse tripole can restore DC selectivity.
      METHODS: Staggered transverse tripoles with quadripolar lateral anodes were
      modeled on the low-thoracic vertebral region (T10-T12) of the spinal cord using
      (a) percutaneous lead with staggered quadripolar lateral anodal configuration
      (PERC QD) and (b) laminotomy lead with staggered quadripolar lateral anodal
      configuration (LAM QD), of the same contact dimensions. The commercially
      available LAM 565 surgical lead with 16 widely spaced contacts was also modeled.
      For comparison with PERC QD, staggered transverse tripoles with dual lateral
      anodes were modeled by using percutaneous lead with staggered dual lateral anodal
      configuration (PERC ST). RESULTS: The PERC QD improved the depth of DC
      penetration and enabled selective recruitment of DCs in comparison with PERC ST.
      Mediolateral selectivity of DCs could not be achieved with the LAM 565.
      CONCLUSION: Stimulation using PERC QD improves anodal shielding of dorsal roots
      and restores DC selectivity. Based on our modeling study, we hypothesize that, in
      clinical practice, LAM QD can provide an improved performance compared with the
      PERC QD. Our model also predicts that the same configuration realized on the
      commercial LAM 565 surgical lead with widely spaced contacts cannot selectively
      stimulate DCs essential in treating low-back pain.

PMID- 23151621
TI  - Infection risk in neurointervention and cerebral angiography.
AB  - BACKGROUND: The risk of infection with cerebral angiography and
      neurointerventional procedures has not been defined. Likewise, although the use
      of routine prophylactic antibiotics has been advocated by some
      neurointerventionalists, the utility of prophylactic antibiotics in this setting
      has not been determined. OBJECTIVE: To determine the rate of infection associated
      with neuroangiographic procedures in a clinical setting in which prophylactic
      antibiotics are not routinely given. METHODS: All cerebral angiograms and
      neurointerventional procedures done by a single neurointerventionalist over a
      recent 7-year period were retrospectively reviewed. Patients with infections
      directly attributable to the procedure were identified. A sample size calculation
      was done to determine the necessary size of a randomized, controlled trial aimed
      at determining whether prophylactic antibiotics can lower the rate of infection.
      RESULTS: Among a total of 2918 cerebral angiograms and neurointerventional
      procedures done without prophylactic antibiotics, there were 3 infections (0.1%)
      attributable to the procedure. All infections were localized femoral artery
      infections with no systemic complications. One infection occurred in a patient
      who was immunosuppressed because of treatment for cancer. Two of the patients
      required surgical debridement; all were treated with intravenous antibiotics with
      resolution of all infections. There were no central nervous system infections and
      no deaths associated with the infections. CONCLUSION: These data suggest that the
      overall risk of infection associated with most neuroangiographic procedures is
      very low. Prophylactic antibiotic use may be a reasonable option for selected
      patients but is probably unnecessary for standard use in the context of
      meticulous care during procedures.

PMID- 23151622
TI  - Vessel wall magnetic resonance imaging identifies the site of rupture in patients
      with multiple intracranial aneurysms:  proof of principle.
AB  - BACKGROUND: High-resolution magnetic resonance vessel wall imaging (MR-VWI) is
      increasingly used to study steno-occlusive cerebrovascular disease, but has not
      yet been applied to patients with aneurysmal subarachnoid hemorrhage (SAH).
      OBJECTIVE: To study the ability of high-resolution MR-VWI to determine the site
      of rupture in patients with aneurysmal SAH. METHODS: Medical records of patients
      admitted with aneurysmal SAH between December 2011 and May 2012 were reviewed. MR
      VWI was routinely performed for patients treated in the IMRIS Neurovascular Suite
      immediately before definitive treatment of the ruptured aneurysm. RESULTS: We
      report for the first time high-resolution MR-VWI in 5 patients with aneurysmal
      SAH. Three patients harbored multiple intracranial aneurysms. The ruptured
      aneurysms demonstrated thick vessel wall enhancement in all cases. None of the
      associated unruptured aneurysms demonstrated this MR imaging finding. CONCLUSION:
      High-resolution MR-VWI identified the site of rupture in patients with aneurysmal
      SAH, including those patients harboring multiple intracranial aneurysms. It may
      represent a useful tool in the investigation of aneurysmal SAH.

PMID- 23151624
TI  - The structure of a thermostable mutant of pro-papain reveals its activation
      mechanism.
AB  - Papain is the archetype of a broad class of cysteine proteases (clan C1A) that
      contain a pro-peptide in the zymogen form which is required for correct folding
      and spatio-temporal regulation of proteolytic activity in the initial stages
      after expression. This study reports the X-ray structure of the zymogen of a
      thermostable mutant of papain at 2.6 A resolution. The overall structure, in
      particular that of the mature part of the protease, is similar to those of other
      members of the family. The structure provides an explanation for the molecular
      basis of the maintenance of latency of the proteolytic activity of the zymogen by
      its pro-segment at neutral pH. The structural analysis, together with biochemical
      and biophysical studies, demonstrated that the pro-segment of the zymogen
      undergoes a rearrangement in the form of a structural loosening at acidic pH
      which triggers the proteolytic activation cascade. This study further explains
      the bimolecular stepwise autocatalytic activation mechanism by limited
      proteolysis of the zymogen of papain at the molecular level. The possible factors
      responsible for the higher thermal stability of the papain mutant have also been
      analyzed.

PMID- 23151623
TI  - Thymosin beta4 reduces senescence of endothelial progenitor cells via the
      PI3K/Akt/eNOS signal transduction pathway.
AB  - We previously demonstrated that thymosin beta4 (Tbeta4) regulates a variety of
      endothelial progenitor cell (EPC) functions, including cell migration,
      proliferation, survival and angiogenesis. However, the effect of Tbeta4 on the
      senescence of circulating EPCs remains unclear. In the present study, the effect
      of Tbeta4 on EPC senescence and the signal transduction pathways involved in this
      process was investigated. Circulating EPCs isolated from healthy volunteers were
      cultured in the absence or presence of Tbeta4 and various signal cascade
      inhibitors. Tbeta4 inhibited EPC senescence in a concentration-dependent manner.
      In addition, Tbeta4 increased telomerase activity and expression of telomerase
      reverse transcriptase mRNA in EPCs. Tbeta4 also regulated the expression of p21,
      p27 and cyclin D1. The effects of Tbeta4 on EPC senescence were eliminated by the
      phosphoinositide 3'-kinase (PI3K) inhibitor, wortmannin and the endothelial
      nitric oxide synthase inhibitor, L-nitroarginine methyl ester hydrochloride (L
      NAME). In conclusion, the inhibitory effect on EPC senescence mediated by Tbeta4
      may be attributed, at least in part, to activation of the PI3K-Akt-eNOS signaling
      pathway.

PMID- 23151625
TI  - Structure-activity correlations of variant forms of the B pentamer of Escherichia
      coli type II heat-labile enterotoxin LT-IIb with Toll-like receptor 2 binding.
AB  - The pentameric B subunit of the type II heat-labile enterotoxin of Escherichia
      coli (LT-IIb-B(5)) is a potent signaling molecule capable of modulating innate
      immune responses. It has previously been shown that LT-IIb-B(5), but not the LT
      IIb-B(5) Ser74Asp variant [LT-IIb-B(5)(S74D)], activates Toll-like receptor
      (TLR2) signaling in macrophages. Consistent with this, the LT-IIb-B(5)(S74D)
      variant failed to bind TLR2, in contrast to LT-IIb-B(5) and the LT-IIb-B(5)
      Thr13Ile [LT-IIb-B(5)(T13I)] and LT-IIb-B(5) Ser74Ala [LT-IIb-B(5)(S74A)]
      variants, which displayed the highest binding activity to TLR2. Crystal
      structures of the Ser74Asp, Ser74Ala and Thr13Ile variants of LT-IIb-B(5) have
      been determined to 1.90, 1.40 and 1.90 A resolution, respectively. The structural
      data for the Ser74Asp variant reveal that the carboxylate side chain points into
      the pore, thereby reducing the pore size compared with that of the wild-type or
      the Ser74Ala variant B pentamer. On the basis of these crystallographic data, the
      reduced TLR2-binding affinity of the LT-IIb-B(5)(S74D) variant may be the result
      of the pore of the pentamer being closed. On the other hand, the explanation for
      the enhanced TLR2-binding activity of the LT-IIb-B(5)(S74A) variant is more
      complex as its activity is greater than that of the wild-type B pentamer, which
      also has an open pore as the Ser74 side chain points away from the pore opening.
      Data for the LT-IIb-B(5)(T13I) variant show that four of the five variant side
      chains point to the outside surface of the pentamer and one residue points
      inside. These data are consistent with the lack of binding of the LT-IIb
      B(5)(T13I) variant to GD1a ganglioside.

PMID- 23151627
TI  - AMPLE: a cluster-and-truncate approach to solve the crystal structures of small
      proteins using rapidly computed ab initio models.
AB  - Protein ab initio models predicted from sequence data alone can enable the
      elucidation of crystal structures by molecular replacement. However, the
      calculation of such ab initio models is typically computationally expensive.
      Here, a computational pipeline based on the clustering and truncation of cheaply
      obtained ab initio models for the preparation of structure ensembles is
      described. Clustering is used to select models and to quantitatively predict
      their local accuracy, allowing rational truncation of predicted inaccurate
      regions. The resulting ensembles, with or without rapidly added side chains,
      solved 43% of all test cases, with an 80% success rate for all-alpha proteins. A
      program implementing this approach, AMPLE, is included in the CCP4 suite of
      programs. It only requires the input of a FASTA sequence file and a diffraction
      data file. It carries out the modelling using locally installed Rosetta, creates
      search ensembles and automatically performs molecular replacement and model
      rebuilding.

PMID- 23151626
TI  - Structure of the catalytic domain of the Salmonella virulence factor SseI.
AB  - SseI is secreted into host cells by Salmonella and contributes to the
      establishment of systemic infections. The crystal structure of the C-terminal
      domain of SseI has been solved to 1.70 A resolution, revealing it to be a member
      of the cysteine protease superfamily with a catalytic triad consisting of Cys178,
      His216 and Asp231 that is critical to its virulence activities. Structure-based
      analysis revealed that SseI is likely to possess either acyl hydrolase or
      acyltransferase activity, placing this virulence factor in the rapidly growing
      class of enzymes of this family utilized by bacterial pathogens inside eukaryotic
      cells.

PMID- 23151628
TI  - Structural studies of human insulin cocrystallized with phenol or resorcinol via
      powder diffraction.
AB  - The effects of the ligands phenol and resorcinol on the crystallization of human
      insulin have been investigated as a function of pH. Powder diffraction data were
      used to characterize several distinct polymorphic forms. A previously unknown
      polymorph with monoclinic symmetry (P2(1)) was identified for both types of
      ligand with similar characteristics [the unit-cell parameters for the insulin
      resorcinol complex were a = 114.0228 (8), b = 335.43 (3), c = 49.211 (6) A, beta
      = 101.531 (8) degrees ].

PMID- 23151629
TI  - Substrate channels revealed in the trimeric Lactobacillus reuteri bacterial
      microcompartment shell protein PduB.
AB  - Lactobacillus reuteri metabolizes two similar three-carbon molecules, 1,2
      propanediol and glycerol, within closed polyhedral subcellular bacterial
      organelles called bacterial microcompartments (metabolosomes). The outer shell of
      the propanediol-utilization (Pdu) metabolosome is composed of hundreds of mainly
      hexagonal protein complexes made from six types of protein subunits that share
      similar domain structures. The structure of the bacterial microcompartment
      protein PduB has a tandem structural repeat within the subunit and assembles into
      a trimer with pseudo-hexagonal symmetry. This trimeric structure forms sheets in
      the crystal lattice and is able to fit within a polymeric sheet of the major
      shell component PduA to assemble a facet of the polyhedron. There are three pores
      within the trimer and these are formed between the tandem repeats within the
      subunits. The structure shows that each of these pores contains three glycerol
      molecules that interact with conserved residues, strongly suggesting that these
      subunit pores channel glycerol substrate into the metabolosome. In addition to
      the observation of glycerol occupying the subunit channels, the presence of
      glycerol on the molecular threefold symmetry axis suggests a role in locking
      closed the central region.

PMID- 23151630
TI  - Structural basis for the influence of a single mutation K145N on the
      oligomerization and photoswitching rate of Dronpa.
AB  - The crystal structure of the on-state of PDM1-4, a single-mutation variant of the
      photochromic fluorescent protein Dronpa, is reported at 1.95 A resolution. PDM1-4
      is a Dronpa variant that possesses a slower off-switching rate than Dronpa and
      thus can effectively increase the image resolution in subdiffraction optical
      microscopy, although the precise molecular basis for this change has not been
      elucidated. This work shows that the Lys145Asn mutation in PDM1-4 stabilizes the
      interface available for dimerization, facilitating oligomerization of the
      protein. No significant changes were observed in the chromophore environment of
      PDM1-4 compared with Dronpa, and the ensemble absorption and emission properties
      of PDM1-4 were highly similar to those of Dronpa. It is proposed that the slower
      off-switching rate in PDM1-4 is caused by a decrease in the potential flexibility
      of certain beta-strands caused by oligomerization along the AC interface.

PMID- 23151631
TI  - X-ray study of the conformational changes in the molecule of phosphopantetheine
      adenylyltransferase from Mycobacterium tuberculosis during the catalyzed
      reaction.
AB  - Structures of recombinant phosphopantetheine adenylyltransferase (PPAT) from
      Mycobacterium tuberculosis (PPATMt) in the apo form and in complex with the
      substrate ATP were determined at 1.62 and 1.70 A resolution, respectively, using
      crystals grown in microgravity by the counter-diffusion method. The ATP molecule
      of the PPATMt-ATP complex was located with full occupancy in the active-site
      cavity. Comparison of the solved structures with previously determined structures
      of PPATMt complexed with the reaction product dephosphocoenzyme A (dPCoA) and the
      feedback inhibitor coenzyme A (CoA) was performed using superposition on C(alpha)
      atoms. The peculiarities of the arrangement of the ligands in the active-site
      cavity of PPATMt are described. The conformational states of the PPAT molecule in
      the consequent steps of the catalyzed reaction in the apo enzyme and the enzyme
      substrate and enzyme-product complexes are characterized. It is shown that the
      binding of ATP and dPCoA induces the rearrangement of a short part of the
      polypeptide chain restricting the active-site cavity in the subunits of the
      hexameric enzyme molecule. The changes in the quaternary structure caused by this
      rearrangement are accompanied by a variation of the size of the inner water
      filled channel which crosses the PPAT molecule along the threefold axis of the
      hexamer. The molecular mechanism of the observed changes is described.

PMID- 23151632
TI  - Structural insights into the specific anti-HIV property of actinohivin: structure
      of its complex with the alpha(1-2)mannobiose moiety of gp120.
AB  - Actinohivin (AH) is an actinomycete lectin with a potent specific anti-HIV
      activity. In order to clarify the structural evidence for its specific binding to
      the alpha(1-2)mannobiose (MB) moiety of the D1 chains of high-mannose-type
      glycans (HMTGs) attached to HIV-1 gp120, the crystal structure of AH in complex
      with MB has been determined. The AH molecule is composed of three identical
      structural modules, each of which has a pocket in which an MB molecule is bound
      adopting a bracket-shaped conformation. This conformation is stabilized through
      two weak C-H...O hydrogen bonds facilitated by the alpha(1-2) linkage. The
      binding features in the three pockets are quite similar to each other, in
      accordance with the molecular pseudo-threefold symmetry generated from the three
      tandem repeats in the amino-acid sequence. The shape of the pocket can accept two
      neighbouring hydroxyl groups of the O(3) and O(4) atoms of the equatorial
      configuration of the second mannose residue. To recognize these atoms through
      hydrogen bonds, an Asp residue is located at the bottom of each pocket. Tyr and
      Leu residues seem to block the movement of the MB molecules. Furthermore, the
      O(1) atom of the axial configuration of the second mannose residue protrudes from
      each pocket into an open space surrounded by the conserved hydrophobic residues,
      suggesting an additional binding site for the third mannose residue of the
      branched D1 chain of HMTGs. These structural features provide strong evidence
      indicating that AH is only highly specific for MB and would facilitate the highly
      specific affinity of AH for any glycoprotein carrying many HMTGs, such as HIV-1
      gp120.

PMID- 23151634
TI  - ScrewFit: combining localization and description of protein secondary structure.
AB  - A new application of the ScrewFit algorithm [Kneller & Calligari (2006), Acta
      Cryst. D62, 302-311] is presented which adds the detection of protein secondary
      structure elements to their detailed geometrical description in terms of a curve
      with intrinsic torsion. The extension is based on confidence and persistence
      criteria for the ScrewFit parameters which are established by analyzing the
      structural fluctuations of standard motifs in the SCOP fold classes. The
      agreement with the widely used DSSP method is comparable with the general
      consensus among other methods in the literature. This combination of secondary
      structure detection and analysis is illustrated for the enzyme adenylate kinase.

PMID- 23151635
TI  - Measurement of detergent concentration using 2,6-dimethylphenol in membrane
      protein crystallization.
AB  - Methods have previously been developed to measure detergent concentration in
      membrane-protein samples, but most have significant limitations, such as
      requiring specialized equipment or consuming a significant amount of precious
      sample. This work explores the use of 2,6-dimethylphenol in a phenol-sulfuric
      acid assay to accurately measure the concentration of common glycosidic-based
      detergents used in crystallization. This method is amenable to routine laboratory
      use, provides excellent sensitivity and significantly reduces the sample volume
      required. Using an Escherichia coli tyrosine kinase (Etk) construct as an
      example, it is shown that the crystallization potential of Etk is directly
      influenced by measurable changes in detergent concentration.

PMID- 23151633
TI  - Dimeric structure of the N-terminal domain of PriB protein from
      Thermoanaerobacter tengcongensis solved ab initio.
AB  - PriB is one of the components of the bacterial primosome, which catalyzes the
      reactivation of stalled replication forks at sites of DNA damage. The N-terminal
      domain of the PriB protein from the thermophilic bacterium Thermoanaerobacter
      tengcongensis (TtePriB) was expressed and its crystal structure was solved at the
      atomic resolution of 1.09 A by direct methods. The protein chain, which
      encompasses the first 104 residues of the full 220-residue protein, adopts the
      characteristic oligonucleotide/oligosaccharide-binding (OB) structure consisting
      of a five-stranded beta-barrel filled with hydrophobic residues and equipped with
      four loops extending from the barrel. In the crystal two protomers dimerize,
      forming a six-stranded antiparallel beta-sheet. The structure of the N-terminal
      OB domain of T. tengcongensis shows significant differences compared with
      mesophile PriBs. While in all other known structures of PriB a dimer is formed by
      two identical OB domains in separate chains, TtePriB contains two consecutive OB
      domains in one chain. However, sequence comparison of both the N-terminal and the
      C-terminal domains of TtePriB suggests that they have analogous structures and
      that the natural protein possesses a structure similar to a dimer of two N
      terminal domains.

PMID- 23151636
TI  - Nearest-cell: a fast and easy tool for locating crystal matches in the PDB.
AB  - When embarking upon X-ray diffraction data collection from a potentially novel
      macromolecular crystal form, it can be useful to ascertain whether the measured
      data reflect a crystal form that is already recorded in the Protein Data Bank
      and, if so, whether it is part of a large family of related structures. Providing
      such information to crystallographers conveniently and quickly, as soon as the
      first images have been recorded and the unit cell characterized at an X-ray
      beamline, has the potential to save time and effort as well as pointing to
      possible search models for molecular replacement. Given an input unit cell, and
      optionally a space group, Nearest-cell rapidly scans the Protein Data Bank and
      retrieves near-matches.

PMID- 23151637
TI  - Microbial diversity and impact on carbonate geochemistry across a changing
      geochemical gradient in a karst aquifer.
AB  - Although microbes are known to influence karst (carbonate) aquifer ecosystem
      level processes, comparatively little information is available regarding the
      diversity of microbial activities that could influence water quality and
      geological modification. To assess microbial diversity in the context of aquifer
      geochemistry, we coupled 16S rRNA Sanger sequencing and 454 tag pyrosequencing to
      in situ microcosm experiments from wells that cross the transition from fresh to
      saline and sulfidic water in the Edwards Aquifer of central Texas, one of the
      largest karst aquifers in the United States. The distribution of microbial groups
      across the transition zone correlated with dissolved oxygen and sulfide
      concentration, and significant variations in community composition were explained
      by local carbonate geochemistry, specifically calcium concentration and
      alkalinity. The waters were supersaturated with respect to prevalent aquifer
      minerals, calcite and dolomite, but in situ microcosm experiments containing
      these minerals revealed significant mass loss from dissolution when colonized by
      microbes. Despite differences in cell density on the experimental surfaces,
      carbonate loss was greater from freshwater wells than saline, sulfidic wells.
      However, as cell density increased, which was correlated to and controlled by
      local geochemistry, dissolution rates decreased. Surface colonization by
      metabolically active cells promotes dissolution by creating local disequilibria
      between bulk aquifer fluids and mineral surfaces, but this also controls rates of
      karst aquifer modification. These results expand our understanding of microbial
      diversity in karst aquifers and emphasize the importance of evaluating active
      microbial processes that could affect carbonate weathering in the subsurface.

PMID- 23151639
TI  - Shifts of functional gene representation in wheat rhizosphere microbial
      communities under elevated ozone.
AB  - Although the influence of ozone (O(3)) on plants has been well studied in
      agroecosystems, little is known about the effect of elevated O(3) (eO(3)) on soil
      microbial functional communities. Here, we used a comprehensive functional gene
      array (GeoChip 3.0) to investigate the functional composition, and structure of
      rhizosphere microbial communities of Yannong 19 (O(3)-sensitive) and Yangmai 16
      (O(3)-relatively sensitive) wheat (Triticum aestivum L.) cultivars under eO(3).
      Compared with ambient O(3) (aO(3)), eO(3) led to an increase in soil pH and total
      carbon (C) percentages in grain and straw of wheat plants, and reduced grain
      weight and soil dissolved organic carbon (DOC). Based on GeoChip hybridization
      signal intensities, although the overall functional structure of rhizosphere
      microbial communities did not significantly change by eO(3) or cultivars, the
      results showed that the abundance of specific functional genes involved in C
      fixation and degradation, nitrogen (N) fixation, and sulfite reduction did
      significantly (P<0.05) alter in response to eO(3) and/or wheat cultivars. Also,
      Yannong 19 appeared to harbor microbial functional communities in the rhizosphere
      more sensitive in response to eO(3) than Yangmai 16. Additionally, canonical
      correspondence analysis suggested that the functional structure of microbial
      community involved in C cycling was largely shaped by soil and plant properties
      including pH, DOC, microbial biomass C, C/N ratio and grain weight. This study
      provides new insight into our understanding of the influence of eO(3) and wheat
      cultivars on soil microbial communities.

PMID- 23151640
TI  - The unaccounted yet abundant nitrous oxide-reducing microbial community: a
      potential nitrous oxide sink.
AB  - Nitrous oxide (N(2)O) is a major radiative forcing and stratospheric ozone
      depleting gas emitted from terrestrial and aquatic ecosystems. It can be
      transformed to nitrogen gas (N(2)) by bacteria and archaea harboring the N(2)O
      reductase (N(2)OR), which is the only known N(2)O sink in the biosphere. Despite
      its crucial role in mitigating N(2)O emissions, knowledge of the N(2)OR in the
      environment remains limited. Here, we report a comprehensive phylogenetic
      analysis of the nosZ gene coding the N(2)OR in genomes retrieved from public
      databases. The resulting phylogeny revealed two distinct clades of nosZ, with one
      unaccounted for in studies investigating N(2)O-reducing communities. Examination
      of N(2)OR structural elements not considered in the phylogeny revealed that the
      two clades differ in their signal peptides, indicating differences in the
      translocation pathway of the N(2)OR across the membrane. Sequencing of
      environmental clones of the previously undetected nosZ lineage in various
      environments showed that it is widespread and diverse. Using quantitative PCR, we
      demonstrate that this clade was most often at least as abundant as the other,
      thereby more than doubling the known extent of the overall N(2)O-reducing
      community in the environment. Furthermore, we observed that the relative
      abundance of nosZ from either clade varied among habitat types and environmental
      conditions. Our results indicate a physiological dichotomy in the diversity of
      N(2)O-reducing microorganisms, which might be of importance for understanding the
      relationship between the diversity of N(2)O-reducing microorganisms and N(2)O
      reduction in different ecosystems.

PMID- 23151641
TI  - Pre-exposure to drought increases the resistance of tropical forest soil
      bacterial communities to extended drought.
AB  - Global climate models project a decrease in the magnitude of precipitation in
      tropical regions. Changes in rainfall patterns have important implications for
      the moisture content and redox status of tropical soils, yet little is known
      about how these changes may affect microbial community structure. Specifically,
      does exposure to prior stress confer increased resistance to subsequent
      perturbation? Here we reduced the quantity of precipitation throughfall to
      tropical forest soils in the Luquillo Mountains, Puerto Rico. Treatments included
      newly established throughfall exclusion plots (de novo excluded), plots
      undergoing reduction for a second time (pre-excluded) and ambient control plots.
      Ten months of throughfall exclusion led to a small but statistically significant
      decline in soil water potential and bacterial populations clearly adapted to
      increased osmotic stress. Although the water potential decline was small and
      microbial biomass did not change, phylogenetic diversity in the de novo-excluded
      plots decreased by ~40% compared with the control plots, yet pre-excluded plots
      showed no significant change. On the other hand, the relative abundances of
      bacterial taxa in both the de novo-excluded and pre-excluded plots changed
      significantly with throughfall exclusion compared with control plots. Changes in
      bacterial community structure could be explained by changes in soil pore water
      chemistry and suggested changes in soil redox. Soluble iron declined in treatment
      plots and was correlated with decreased soluble phosphorus concentrations, which
      may have significant implications for microbial productivity in these P-limited
      systems.

PMID- 23151643
TI  - Strain-specific functional and numerical responses are required to evaluate
      impacts on predator-prey dynamics.
AB  - We use strains recently collected from the field to establish cultures; then,
      through laboratory studies we investigate how among strain variation in protozoan
      ingestion and growth rates influences population dynamics and intraspecific
      competition. We focused on the impact of changing temperature because of its well
      established effects on protozoan rates and its ecological relevance, from daily
      fluctuations to climate change. We show, first, that there is considerable inter
      strain variability in thermal sensitivity of maximum growth rate, revealing
      distinct differences among multiple strains of our model species Oxyrrhis marina.
      We then intensively examined two representative strains that exhibit distinctly
      different thermal responses and parameterised the influence of temperature on
      their functional and numerical responses. Finally, we assessed how these
      responses alter predator-prey population dynamics. We do this first considering a
      standard approach, which assumes that functional and numerical responses are
      directly coupled, and then compare these results with a novel framework that
      incorporates both functional and numerical responses in a fully parameterised
      model. We conclude that: (i) including functional diversity of protozoa at the
      sub-species level will alter model predictions and (ii) including directly
      measured, independent functional and numerical responses in a model can provide a
      more realistic account of predator-prey dynamics.

PMID- 23151642
TI  - Comparative analysis of the distribution of segmented filamentous bacteria in
      humans, mice and chickens.
AB  - Segmented filamentous bacteria (SFB) are indigenous gut commensal bacteria. They
      are commonly detected in the gastrointestinal tracts of both vertebrates and
      invertebrates. Despite the significant role they have in the modulation of the
      development of host immune systems, little information exists regarding the
      presence of SFB in humans. The aim of this study was to investigate the
      distribution and diversity of SFB in humans and to determine their phylogenetic
      relationships with their hosts. Gut contents from 251 humans, 92 mice and 72
      chickens were collected for bacterial genomic DNA extraction and subjected to SFB
      16S rRNA-specific PCR detection. The results showed SFB colonization to be age
      dependent in humans, with the majority of individuals colonized within the first
      2 years of life, but this colonization disappeared by the age of 3 years. Results
      of 16S rRNA sequencing showed that multiple operational taxonomic units of SFB
      could exist in the same individuals. Cross-species comparison among human, mouse
      and chicken samples demonstrated that each host possessed an exclusive
      predominant SFB sequence. In summary, our results showed that SFB display host
      specificity, and SFB colonization, which occurs early in human life, declines in
      an age-dependent manner.

PMID- 23151644
TI  - Geoarchaeota: a new candidate phylum in the Archaea from high-temperature acidic
      iron mats in Yellowstone National Park.
AB  - Geothermal systems in Yellowstone National Park (YNP) provide an outstanding
      opportunity to understand the origin and evolution of metabolic processes
      necessary for life in extreme environments including low pH, high temperature,
      low oxygen and elevated concentrations of reduced iron. Previous phylogenetic
      studies of acidic ferric iron mats from YNP have revealed considerable diversity
      of uncultivated and undescribed archaea. The goal of this study was to obtain
      replicate de novo genome assemblies for a dominant archaeal population inhabiting
      acidic iron-oxide mats in YNP. Detailed analysis of conserved ribosomal and
      informational processing genes indicates that the replicate assemblies represent
      a new candidate phylum within the domain Archaea referred to here as
      'Geoarchaeota' or 'novel archaeal group 1 (NAG1)'. The NAG1 organisms contain
      pathways necessary for the catabolism of peptides and complex carbohydrates as
      well as a bacterial-like Form I carbon monoxide dehydrogenase complex likely used
      for energy conservation. Moreover, this novel population contains genes involved
      in the metabolism of oxygen including a Type A heme copper oxidase, a bd-type
      terminal oxidase and a putative oxygen-sensing protoglobin. NAG1 has a variety of
      unique bacterial-like cofactor biosynthesis and transport genes and a Type3-like
      CRISPR system. Discovery of NAG1 is critical to our understanding of microbial
      community structure and function in extant thermophilic iron-oxide mats of YNP,
      and will provide insight regarding the evolution of Archaea in early Earth
      environments that may have important analogs active in YNP today.

PMID- 23151645
TI  - Are we missing half of the viruses in the ocean?
AB  - Viruses are abundant in the ocean and a major driving force in plankton ecology
      and evolution. It has been assumed that most of the viruses in seawater contain
      DNA and infect bacteria, but RNA-containing viruses in the ocean, which almost
      exclusively infect eukaryotes, have never been quantified. We compared the total
      mass of RNA and DNA in the viral fraction harvested from seawater and using data
      on the mass of nucleic acid per RNA- or DNA-containing virion, estimated the
      abundances of each. Our data suggest that the abundance of RNA viruses rivaled or
      exceeded that of DNA viruses in samples of coastal seawater. The dominant RNA
      viruses in the samples were marine picorna-like viruses, which have small genomes
      and are at or below the detection limit of common fluorescence-based counting
      methods. If our results are typical, this means that counts of viruses and the
      rate measurements that depend on them, such as viral production, are
      significantly underestimated by current practices. As these RNA viruses infect
      eukaryotes, our data imply that protists contribute more to marine viral dynamics
      than one might expect based on their relatively low abundance. This conclusion is
      a departure from the prevailing view of viruses in the ocean, but is consistent
      with earlier theoretical predictions.

PMID- 23151646
TI  - Environmental distribution of coral-associated relatives of apicomplexan
      parasites.
AB  - A lineage of plastid-bearing eukaryotic microbes that is closely related to
      apicomplexan parasites was recently found in a specific association with coral
      reefs (apicomplexan-related lineage-V, or ARL-V). Here, we address the possible
      nature of this association using plastid 'contamination' in fine-scale bacterial
      sequence surveys. In a transect between corals and associated macroalgae, ARL-V
      is specifically associated with the coral, in contrast to all microalgal types
      (including diatoms, haptophytes, pelagophytes and photosynthetic apicomplexan
      relatives, Chromera and Vitrella), which are associated with macroalgae. ARL-V is
      associated with at least 20 species of symbiotic corals through extended time
      periods and large geographic distances. It is significantly enriched in healthy
      coral tissue and shallow reef depths. Altogether, the evidence points to a
      specific relationship between ARL-V and corals, and is suggestive of symbiosis,
      perhaps based on photosynthesis.

PMID- 23151638
TI  - Diversity and population structure of Marine Group A bacteria in the Northeast
      subarctic Pacific Ocean.
AB  - Marine Group A (MGA) is a candidate phylum of Bacteria that is ubiquitous and
      abundant in the ocean. Despite being prevalent, the structural and functional
      properties of MGA populations remain poorly constrained. Here, we quantified MGA
      diversity and population structure in relation to nutrients and O(2)
      concentrations in the oxygen minimum zone (OMZ) of the Northeast subarctic
      Pacific Ocean using a combination of catalyzed reporter deposition fluorescence
      in situ hybridization (CARD-FISH) and 16S small subunit ribosomal RNA (16S rRNA)
      gene sequencing (clone libraries and 454-pyrotags). Estimates of MGA abundance as
      a proportion of total bacteria were similar across all three methods although
      estimates based on CARD-FISH were consistently lower in the OMZ (5.6%+/-1.9%)
      than estimates based on 16S rRNA gene clone libraries (11.0%+/-3.9%) or pyrotags
      (9.9%+/-1.8%). Five previously defined MGA subgroups were recovered in 16S rRNA
      gene clone libraries and five novel subgroups were defined (HF770D10, P262000D03,
      P41300E03, P262000N21 and A714018). Rarefaction analysis of pyrotag data
      indicated that the ultimate richness of MGA was very nearly sampled. Spearman's
      rank analysis of MGA abundances by CARD-FISH and O(2) concentrations resulted in
      significant correlation. Analyzed in more detail by 16S rRNA pyrotag sequencing,
      MGA operational taxonomic units affiliated with subgroups Arctic95A-2 and A714018
      comprised 0.3-2.4% of total bacterial sequences and displayed strong correlations
      with decreasing O(2) concentration. This study is the first comprehensive
      description of MGA diversity using complementary techniques. These results
      provide a phylogenetic framework for interpreting future studies on ecotype
      selection among MGA subgroups, and suggest a potentially important role for MGA
      in the ecology and biogeochemistry of OMZs.

PMID- 23151647
TI  - Spectrum of ocular toxicities from epidermal growth factor receptor inhibitors
      and their intermediate-term follow-up: a five-year review.
AB  - PURPOSE: Epidermal growth factor receptor (EGFR) inhibitors and kinases are
      commonly used in the treatment regimen of various solid tumors including non
      small cell lung, colorectal, head and neck, breast, and pancreatic cancers. The
      aim of this study is to describe common ocular adverse effects associated with
      EGFR inhibitor treatment, outline successful management options, and provide data
      on intermediate-term follow-up of these patients. METHODS: A retrospective chart
      review was performed of all patients presenting to the ophthalmology clinic with
      an adverse ocular effect while on an EGFR inhibitor. Duration of EGFR inhibitor
      treatment, symptoms, diagnosis, and treatment information were collected.
      Statistical analyses were done to ascertain differences in adverse effects based
      on duration and type of EGFR inhibitor treatment using the Fisher exact test.
      RESULTS: The two most common EGFR inhibitors in this group of patients were
      erlotinib and cetuximab. The most common adverse ocular effects for patients on
      EGFR inhibitors were dysfunctional tear syndrome (DTS), followed by blepharitis
      and eyelash changes (trichomegaly and trichiasis). Two patients had epithelial
      defects (corneal abrasions). There was no significant difference in adverse
      effects based on specific EGFR inhibitor medication or duration of treatment.
      Almost all patients were successfully managed with treatment regimens that we
      have outlined in this paper. Intermediate-term follow-up (range 6-17 months)
      showed a persistence of DTS and eyelash changes. CONCLUSION: We present what is,
      to our knowledge, the largest reported cohort of patients with ocular toxicities
      from EGFR inhibitors--the spectrum of eye toxicities, their management, and the
      intermediate-term follow-up of patients with eye toxicities. Awareness of this
      information is important for oncologists and oncology nurses to facilitate proper
      counseling and management/referral of patients developing eye toxicity while on
      EGFR inhibitors.

PMID- 23151648
TI  - Predictors of high score patient-reported barriers to controlling cancer pain: a
      preliminary report.
AB  - PURPOSE: Pain is one of the most common and devastating symptoms in cancer
      patients, and misunderstandings on the patient's part can cause major obstacles
      in pain management. METHOD: We evaluated factors associated with patient's high
      barrier score to managing cancer-associated pain by having 201 patients complete
      the Korean Barriers Questionnaire II, the Brief Pain Inventory--Korean, the
      European Organization for Research and Treatment of Cancer Quality of Life
      Questionnaire Core 30, and the Korean Beck Depression Inventory. The Pain
      Management Index (PMI) was also assessed. RESULTS: The patients were from nine
      oncology clinics in university hospitals and a veterans' hospital in South Korea.
      The median pain score (0-10 scale) was 4, with a median percentage of pain
      improvement during the last 24 h of 70 %. A total of 150 patients (75 %) received
      strong opioids, and 177 (88 %) achieved adequate analgesia (positive PMI). Mean
      scores +/- SD for the Barriers Questionnaire II ranged from 1.5 +/- 1 to 2.8 +/-
      1.1, with the harmful effects subscale the highest. In the multiple regression
      model, depression was significantly associated with total barrier score to pain
      management (p < 0.0001). Pain reduction was significantly associated with the
      fatalism subscale. CONCLUSIONS: Depression was associated with high barrier score
      in patients with cancer pain. Management of cancer pain should include screening
      for depression, and management of depression could reduce patient-reported
      barriers to pain management.

PMID- 23151649
TI  - Assessment of patient-reported measures of bowel function before and after pelvic
      radiotherapy: an ancillary study of the North Central Cancer Treatment Group
      study N00CA.
AB  - PURPOSE: The Bowel Function Questionnaire (BFQ) has been used in clinical trials
      to assess symptoms during and after pelvic radiotherapy (RT). This study
      evaluated the importance of symptoms in the BFQ from a patient perspective.
      METHODS: Patients reported presence or absence of symptoms and rated importance
      of symptoms at baseline, 4 weeks after completion of pelvic RT, and 12 and 24
      months after RT. The BFQ measured overall quality of life (QOL) and symptoms of
      nocturnal bowel movements, incontinence, clustering, need for protective
      clothing, inability to differentiate stool from gas, liquid bowel movements,
      urgency, cramping, and bleeding. Bowel movement frequency also was recorded. A
      content validity questionnaire (CVQ) was used to rate symptoms as "not very
      important," "moderately unimportant," "neutral," "moderately important," or "very
      important." RESULTS: Most of the 125 participating patients rated all symptoms as
      moderately or very important. Generally, patients gave similar ratings for
      symptom importance at all study points, and ratings were independent of whether
      the patient experienced the symptom. Measures of greatest importance (moderately
      or very important) at baseline were ability to control bowel movements (94 %),
      not having to wear protective clothing (90 %), and not having rectal bleeding (94
      %). With the exception of need for protective clothing, the presence of a symptom
      at 4 weeks was associated with significantly worse QOL (P < .01 for all).
      CONCLUSIONS: The BFQ has excellent content validity. Patients rated most symptoms
      as moderately or very important, indicating the BFQ is an appropriate tool for
      symptom assessment during and after pelvic RT.

PMID- 23151650
TI  - Efficacy of prophylactic lamivudine to prevent hepatitis B virus reactivation in
      B-cell lymphoma treated with rituximab-containing chemotherapy.
AB  - PURPOSE: Reactivation of hepatitis B virus (HBV) is a common complication in
      patients with HBV infection who receive cytotoxic chemotherapy. In rituximab
      containing chemotherapy for B-cell lymphoma, severe hepatitis due to HBV
      reactivation occurred. The aim of this study is to estimate the effect of
      prophylactic lamivudine on the risk of HBV reactivation in patients with HBV
      infection who receive rituximab-containing chemotherapy. METHODS: In this study,
      HBV markers and liver function tests were monitored in 268 consecutive patients
      with B-cell lymphoma, who received rituximab-containing chemotherapy between
      January 2008 and November 2011. Sixty-nine patients (25.7 %) with either chronic
      HBV infection or past HBV infection received prophylaxis with lamivudine 100 mg
      daily by oral intake. RESULTS: In the HBsAg-positive group, six (6/38) patients
      developed hepatitis, only one of which was attributed to HBV reactivation. In the
      HBsAg-negative and HBcAb-positive group, two (2/31) patients developed hepatitis,
      none of which was attributed to HBV reactivation. CONCLUSIONS: These results
      support that prophylactic lamivudine can prevent HBV reactivation for B-cell
      lymphoma with HBV infection who was receiving rituximab-containing chemotherapy.

PMID- 23151652
TI  - Supportive care and not only palliative care in the route of cancer patients.

PMID- 23151651
TI  - In search of the sixth vital sign: cancer care in Romania.
AB  - PURPOSE: Romania still has to adapt and develop psychosocial assessment protocols
      which would allow standardized screening for the sixth vital sign in cancer
      patients, namely distress and quality of life. The present study screens for the
      psychosocial and communication needs of cancer outpatients in palliative care and
      in rehabilitation. These data are also compared with those obtained from a sample
      of cancer inpatients. METHODS: Subjects for this study were recruited from cancer
      care services from the Transylvania region in Romania. A total of 203 persons
      with cancer were included in the screening. Of this number, 68 were in the
      hospitalized group, 71 were from the rehabilitation group, and 64 were palliative
      care cases. FACT-G 4.0 and BDI screening instruments were used in these clinical
      samples. Statistical analysis performed was: associational and comparative
      statistics, one-way analysis of variance. RESULTS: Statistically and clinically
      significant results were found in relation to symptoms of depression, physical
      and functional well-being, and overall quality of life. However, with regard to
      psychosocial well-being, there were no clinically relevant or significant
      differences among cancer patients under hospital treatment, or in rehabilitation
      and palliative care programs. More than 40 % of the cancer patients included in
      our pilot screening were not open to talk about their illness and their related
      needs. CONCLUSIONS: Cancer is an unmet psychosocial challenge to patients and to
      the specialized services, regardless of care type. The urgency of psychosocial
      screening in the Romanian cancer care system is revealed. Based on these
      findings, there is a need for psychosocial screening and related supportive care
      services that need to be integrated into Romania's cancer care programs. A
      recommendation is to pilot psychosocial and supportive care model within the four
      regional cancer care institutions.

PMID- 23151653
TI  - Mass spectrometric techniques for characterizing low-molecular-weight resins used
      as paint varnishes.
AB  - The molecular structure of three low-molecular-weight resins used as paint
      varnishes has been characterized by use of an approach based on three different
      mass spectrometric techniques. We investigated the ketone resin MS2A, the
      aldehyde resin Laropal A81, and the hydrocarbon resin Regalrez 1094, now commonly
      used in restoration. To date, the molecular structures of these resins have not
      been completely elucidated. To improve current knowledge of the chemical
      composition of these materials, information obtained by gas chromatography-mass
      spectrometry (GC/MS), pyrolysis-gas chromatography-mass spectrometry (Py/GC/MS),
      and electrospray ionization mass spectrometry (ESI-Q-ToF) was combined. Analysis,
      in solution, of the whole polymeric fraction of the resins by flow-injection ESI
      Q-ToF, and of the non-polymeric fraction by GC-MS, enabled us to identify
      previously unreported features of the polymer structures. In addition, the Py
      GC/MS profiles that we obtained will help to enhance the databases currently
      available in the literature. The proposed approach can be extended to other low
      molecular-weight resins used as varnishes in conservation.

PMID- 23151654
TI  - The effect of optical substrates on micro-FTIR analysis of single mammalian
      cells.
AB  - The study of individual cells with infrared (IR) microspectroscopy often requires
      living cells to be cultured directly onto a suitable substrate. The surface
      effect of the specific substrates on the cell growth-viability and associated
      biochemistry-as well as on the IR analysis-spectral interference and optical
      artifacts-is all too often ignored. Using the IR beamline, MIRIAM (Diamond Light
      Source, UK), we show the importance of the substrate used for IR absorption
      spectroscopy by analyzing two different cell lines cultured on a range of seven
      optical substrates in both transmission and reflection modes. First, cell
      viability measurements are made to determine the preferable substrates for normal
      cell growth. Successively, synchrotron radiation IR microspectroscopy is
      performed on the two cell lines to determine any genuine biochemically induced
      changes or optical effect in the spectra due to the different substrates.
      Multivariate analysis of spectral data is applied on each cell line to visualize
      the spectral changes. The results confirm the advantage of transmission
      measurements over reflection due to the absence of a strong optical standing wave
      artifact which amplifies the absorbance spectrum in the high wavenumber regions
      with respect to low wavenumbers in the mid-IR range. The transmission spectra
      reveal interference from a more subtle but significant optical artifact related
      to the reflection losses of the different substrate materials. This means that,
      for comparative studies of cell biochemistry by IR microspectroscopy, it is
      crucial that all samples are measured on the same substrate type.

PMID- 23151655
TI  - Effect-based proteomic detection of growth promoter abuse.
AB  - Unregulated growth promoter use in food-producing animals is an issue of concern
      both from food safety and animal welfare perspectives. However, the monitoring of
      such practices is analytically challenging due to the concerted actions of users
      to evade detection. Techniques based on the monitoring of biological responses to
      exogenous administrations have been proposed as more sensitive methods to
      identify treated animals. This study has, for the first time, profiled plasma
      proteome responses in bovine animals to treatment with nortestosterone decanoate
      and 17beta-oestradiol benzoate, followed by dexamethasone administration. Two
      dimensional fluorescence differential in-gel electrophoresis analysis revealed a
      series of hepatic and acute-phase proteins within plasma whose levels were up- or
      down-regulated within phases of the treatment regime. Surface plasmon resonance
      (SPR) immuno-assays were developed to quantify responses of identified protein
      markers during the experimental treatment study with a view to developing methods
      which can be used as screening tools for growth promoter abuse detection. SPR
      analysis demonstrated the potential for plasma proteins to be used as indicative
      measures of growth promoter administrations and concludes that the sensitivity
      and robustness of any detection approach based on plasma proteome analysis would
      benefit from examination of a range of proteins representative of diverse
      biological processes rather being reliant on specific individual markers.

PMID- 23151656
TI  - Gold nanorod separation and characterization by asymmetric-flow field flow
      fractionation with UV-Vis detection.
AB  - The application of asymmetric-flow field flow fractionation (A4F) for low aspect
      ratio gold nanorod (GNR) fractionation and characterization was comprehensively
      investigated. We report on two novel aspects of this application. The first
      addresses the analytical challenge involved in the fractionation of positively
      charged nanoparticles by A4F, due to the interaction that exists between the
      negatively charged native membrane and the analyte. We show that the mobile phase
      composition is a critical parameter for controlling fractionation and mitigating
      the membrane-analyte interaction. A mixture of ammonium nitrate and cetyl
      trimethyl ammonium bromide at different molar ratios enables separation of GNRs
      with high recovery. The second aspect is the demonstration of shape-based
      separation of GNRs in A4F normal mode elution (i.e., Brownian mode). We show that
      the elution of GNRs is due both to aspect ratio and a steric-entropic
      contribution for GNRs with the same diameter. This latter effect can be explained
      by their orientation vector inside the A4F channel. Our experimental results
      demonstrate the relevance of the theory described by Beckett and Giddings for non
      spherical fractionation (Beckett and Giddings, J Colloid and Interface Sci
      186(1):53-59, 1997). However, it is shown that this theory has its limit in the
      case of complex GNR mixtures, and that shape (i.e., aspect ratio) is the
      principal material parameter controlling elution of GNRs in A4F; the apparent
      translational diffusion coefficient of GNRs increases with aspect ratio. Finally,
      the performance of the methodology developed in this work is evaluated by the
      fractionation and characterization of individual components from a mixture of GNR
      aspect ratios.

PMID- 23151658
TI  - A vital assay.

PMID- 23151657
TI  - Inhibition of miR-96 expression reduces cell proliferation and clonogenicity of
      HepG2 hepatoma cells.
AB  - microRNAs (miRNAs) are negative regulators of gene expression and can function as
      tumor suppressors or oncogenes. Several miRNAs are associated with the
      development of hepatocellular carcinoma (HCC). miR-96 has been closely associated
      with cell proliferation and clonogenicity. Upregulation of miR-96 has been
      observed in various types of cancer. However, the biological function of miR-96
      in hepatocarcinogenesis remains largely unknown. In this study, we demonstrated
      that miR-96 was upregulated in HCC and inhibition of miR-96 significantly
      suppressed HCC cell proliferation and colony formation. The expression levels of
      forkhead box O1 (FOXO1) and forkhead box O3a (FOXO3a) were upregulated when miR
      96 was inhibited in HCC cells and the inhibition of FOXO1 and FOXO3a promoted HCC
      cell proliferation and colony formation. Collectively, these data reveal an
      important contribution of miR-96 to hepatocarcinogenesis and suggest a role for
      FOXO1 and FOXO3a dysregulation in this process. Thus, the use of a synthetic
      inhibitor of miR-96 may be a promising approach for the treatment of HCC.

PMID- 23151659
TI  - Autophagy: STAT3 maintains order.

PMID- 23151660
TI  - The conversion of H(2)S to sulfane sulfur.

PMID- 23151661
TI  - Chromosome biology: mixing it up.

PMID- 23151665
TI  - Small RNAs: controlling maturity.

PMID- 23151664
TI  - The origins of the molecular era of adhesion research.
AB  - Recognition of the importance of cell adhesion grew steadily during the twentieth
      century as it promised answers to fundamental questions in diverse fields that
      included cell biology, developmental biology, tumorigenesis, immunology and
      neurobiology. However, the route towards a better understanding of its molecular
      basis was long and difficult, with many false starts. Major progress was made in
      the late 1970s to late 1980s with the identification of the major families of
      adhesion molecules, including integrins and cadherins. This in turn set the stage
      for the explosive growth in adhesion research over the past 25 years.

PMID- 23151663
TI  - The complex world of WNT receptor signalling.
AB  - 30 years after the identification of WNTs, their signal transduction has become
      increasingly complex, with the discovery of more than 15 receptors and co
      receptors in seven protein families. The recent discovery of three receptor
      classes for the R-spondin family of WNT agonists further adds to this complexity.
      What emerges is an intricate network of receptors that form higher-order ligand
      receptor complexes routing downstream signalling. These are regulated both
      extracellularly by agonists such as R-spondin and intracellularly by post
      translational modifications such as phosphorylation, proteolytic processing and
      endocytosis.

PMID- 23151666
TI  - Activated microglia provide a neuroprotective role by balancing glial cell-line
      derived neurotrophic factor and tumor necrosis factor-alpha secretion after
      subacute cerebral ischemia.
AB  - Microglia are the major immune cells in the central nervous system and play a key
      role in brain injury pathology. However, the role of activated microglia after
      subacute cerebral ischemia (SCI) remains unknown. To address this issue, we
      established a permanent middle cerebral artery occlusion (pMCAO) rat model and
      treated pMCAO rats with N-(6-oxo-5,6-dihydro-phenanthridin-2-yl)-N,N
      dimethylacetamide (PJ34) (an inhibitor of microglial activation), or with vehicle
      alone. Finally, we determined the differences between the PJ34-and vehicle
      treated rats with respect to neurological deficits, infarct volume, neuronal loss
      and the expression of CD11b (a marker of microglial activation), glial cell line
      derived neurotrophic factor (GDNF) and tumor necrosis factor-alpha (TNF-alpha) at
      1, 3 and 7 days after treatment. We found that the PJ34-treated rats had more
      severe neurological deficits and a larger infarct volume and exhibited a
      decreased CD11b expression, more neuronal loss, decreased expression of GDNF mRNA
      and protein but increased expression of TNF-alpha mRNA and protein compared with
      the vehicle-treated rats at 3 and 7 days after treatment. These results indicate
      that activated microglia provide a neuroprotective role through balancing GDNF
      and TNF-alpha expression following SCI.

PMID- 23151667
TI  - Gastric cancer screening compliance is influenced by the weight status.
AB  - Obesity is associated with decreased compliance with cancer screening, but with
      an increased risk for cancer development. However, the relationship between
      weight status and compliance with stomach cancer screening has not been not
      studied as yet. We examined men and women aged between 40 and 80 years from the
      4th Korea National Health and Nutrition Examination Survey from 2007 to 2009. BMI
      was classified into <=18.4 kg/m (underweight), 18.5-22.9 kg/m (normal), 23-24.9
      kg/m (overweight), 25.0-29.9 kg/m (moderate obesity), and >=30.0 kg/m (severe
      obesity). Screening compliance was defined as undergoing stomach cancer screening
      every 2 years with either gastroscopy or upper gastrointestinal series. The
      overall screening rates of stomach cancer were 43.2 (0.9)% for men and 43.4
      (0.8)% for women. After adjustment for covariates, the screening rates were
      higher in overweight men (adjusted odds ratio, 1.19; 95% confidence interval,
      0.98-1.44), with a marginal significance, and significantly lower in women with
      severe obesity (adjusted odds ratio, 0.55; 95% confidence interval, 0.40-0.76).
      The difference was mainly driven by the lower acceptance of gastroscopy rather
      than upper gastrointestinal series. In conclusion, obesity is associated with
      lower compliance with stomach cancer screening in Korean women. Therefore, new
      strategies need to be developed to improve the cancer screening compliance in
      obese women.

PMID- 23151669
TI  - Left ventricular thrombus formation after acute myocardial infarction.

PMID- 23151670
TI  - Effect of NF-kappaB inhibitor on high-mobility group protein B1 expression in a
      COPD rat model.
AB  - The aim of the present study was to investigate the effect of the nuclear factor
      kappaB (NF-kappaB) inhibitor, pyrrolidine dithiocarbamate (PDTC), on high
      mobility group protein B1 (HMGB1) expression in a rat model of chronic
      obstructive pulmonary disease (COPD). The COPD model was developed by
      administering lipopolysaccharides to the airways of rats and smudging (group B).
      In addition, a model of COPD complicated with hypoxia was established by
      administering lipopolysaccharides to the airways of rats, smudging and hypoxia
      (group C). PDTC was administered to the treatment groups by intraperitoneal
      injection. Reverse transcription polymerase chain reaction (RT-PCR) and western
      blot analysis were used to detect the expression of HMGB1 and NF-kappaB in lung
      tissue. RT-PCR and western blot analysis demonstrated that HMGB1 mRNA and protein
      expression in groups B and C increased significantly (P<0.05) compared with
      control group A. In addition, HMGB1 expression in groups B and C gradually
      increased. HMGB1 mRNA and protein expression in groups B1 and C1 decreased
      (P<0.05) compared with B and C. NF-kappaB protein expression in groups B and C
      increased significantly (P<0.05) compared with A. NF-kappaB protein expression in
      groups B1 and C1 decreased compared with B and C. Therefore, HMGB1 mRNA and
      protein expression was identified to be positively correlated with NF-kappaB
      protein expression. The NF-kappaB inhibitor, PDTC, was demonstrated to
      significantly inhibit HMGB1 expression in lung tissues of rats with COPD and this
      mechanism may be associated with the NF-kappaB signal transduction pathway.

PMID- 23151668
TI  - Dual-action inhibitors of HIF prolyl hydroxylases that induce binding of a second
      iron ion.
AB  - Inhibition of the hypoxia-inducible factor (HIF) prolyl hydroxylases (PHD or EGLN
      enzymes) is of interest for the treatment of anemia and ischemia-related
      diseases. Most PHD inhibitors work by binding to the single ferrous ion and
      competing with 2-oxoglutarate (2OG) co-substrate for binding at the PHD active
      site. Non-specific iron chelators also inhibit the PHDs, both in vitro and in
      cells. We report the identification of dual action PHD inhibitors, which bind to
      the active site iron and also induce the binding of a second iron ion at the
      active site. Following analysis of small-molecule iron complexes and application
      of non-denaturing protein mass spectrometry to assess PHD2.iron.inhibitor
      stoichiometry, selected diacylhydrazines were identified as PHD2 inhibitors that
      induce the binding of a second iron ion. Some compounds were shown to inhibit the
      HIF hydroxylases in human hepatoma and renal carcinoma cell lines.

PMID- 23151674
TI  - Cytochrome b5 from Giardia lamblia.
AB  - The protozoan intestinal parasite Giardia lamblia lacks mitochondria and the
      ability to make haem yet encodes several putative haem-binding proteins,
      including three of the cytochrome b(5) family. We cloned one of these (gCYTb5-I)
      and expressed it within Escherichia coli as a soluble holoprotein. UV-visible and
      resonance Raman spectra of gCYTb5-I resemble those of microsomal cytochrome b(5),
      and homology modelling supports a structure in which a pair of invariant
      histidine residues act as axial ligands to the haem iron. The reduction potential
      of gCYTb5-I is -165 mV vs. SHE and is relatively low compared to most values (
      110 to +80 mV) for this class of protein. The amino- and carboxy-terminal
      sequences that flank the central haem-binding core of the Giardia cytochromes are
      highly charged and differ from those of other family members. A core gCYTb5-I
      variant lacking these flanking sequences was also able to bind haem. The presence
      of one actual and two probable functional cytochromes b(5) in Giardia is evidence
      of uncharacterized cytochrome-mediated metabolic processes within this medically
      important protist.

PMID- 23151675
TI  - Analysis of ZNF350/ZBRK1 promoter variants and breast cancer susceptibility in
      non-BRCA1/2 French Canadian breast cancer families.
AB  - ZNF350/ZBRK1 is a transcription factor, which associates with BRCA1 to co-repress
      GADD45A to regulate DNA damage repair, and the expression of ZNF350 is altered in
      different human carcinomas. In a previous study, we identified ZNF350 genomic
      variants potentially involved in breast cancer susceptibility in high-risk non
      BRCA1/2 breast cancer individuals, which pointed toward a potential association
      for variants in the 5'-UTR and promoter regions. Therefore, direct sequencing was
      undertaken and identified 12 promoter variants, whereas haplotype analyses put in
      evidence four common haplotypes with a frequency>2%. However, based on their
      frequency observed in breast cancer and unrelated healthy individuals, these are
      not statistically associated with breast cancer risk. Luciferase promoter assays
      in two breast cancer cell lines identified two haplotypes (H11 and H12)
      stimulating significantly the expression of ZNF350 transcript compared with the
      common haplotype H8. The high expression of the H11 allele was associated with
      the variant c.-874A. Using MatInspector and Transcription Element Search
      softwares, in silico analyses predicted that the variant c.-874A created a
      binding site for the factors c-Myc and myogenin. This study represents the first
      characterization step of the ZNF350 promoter. Additional studies in larger
      cohorts and other populations will be needed to further evaluate whether common
      and/or rare ZNF350 promoter variants and haplotypes could be associated with a
      modest risk of breast cancer.

PMID- 23151676
TI  - A commentary on the history of human populations in the Japanese Archipelago
      inferred from genome-wide SNP data with a special reference to the Ainu and the
      Ryukyuan populations.

PMID- 23151677
TI  - A commentary on confirmation and refinement of an autosomal dominant congenital
      motor nystagmus locus in chromosome 1q31.3-q32.1.

PMID- 23151678
TI  - Impact of four loci on serum tamsulosin hydrochloride concentration.
AB  - Tamsulosin hydrochloride is one of the most potent drugs for treatment of benign
      prostatic hyperplasia (BPH), however, the efficacy of tamsulosin hydrochloride
      varies among individuals. In this study, we measured the maximum serum
      concentration (Cmax) of tamsulosin hydrochloride in 182 of BPH patients and found
      remarkable individual variability. To investigate the genetic factors that
      regulate pharmacokinetics of tamsulosin hydrochloride, we conducted a genome-wide
      association study in these 182 BPH patients. As a result, rs16902947 on
      chromosome 5p13.2, rs7779057 on 7q22.3, rs35681285 on 7p21.2 and rs2122469 on
      8p21.3 indicated possible associations with Cmax of tamsulosin hydrochloride
      (P=1.29 * 10(-7), 2.15 * 10(-7), 4.35 * 10(-7) and 7.03 * 10(-7), respectively),
      although these single-nucleotide polymorphisms (SNPs) did not reach the genome
      wide significance threshold after Bonferroni correction. As these associated SNPs
      showed additive effects on serum tamsulosin hydrochloride concentration, we
      defined the 'Cmax prediction index' based on genotypes of these SNPs. This index
      clearly associated with Cmax values (P=4.5 * 10(-6)), indicating the possible
      roles of these four variants in tamsulosin hydrochloride pharmacokinetics. Our
      findings would partially explain the variability of the response to the
      tamsulosin hydrochloride treatment.

PMID- 23151680
TI  - One hundred years of helicene chemistry. Part 3: applications and properties of
      carbohelicenes.
AB  - Carbohelicenes are a class of fascinating chiral helical molecules which have a
      rich history in chemistry. Over a period of almost 100 years, chemists have
      developed many methods to prepare them in a racemic or in a non-racemic form.
      They also possess a series of interesting chiral, physical, electronic and
      optical properties. However, their utilization in chemistry or chemistry-related
      fields has rarely appeared in a detailed and comprehensive review. It is the
      purpose of this review to collect fundamental applications and functions
      involving carbohelicenes in various disciplines such as in materials science, in
      nanoscience, in biological chemistry and in supramolecular chemistry. From the
      numerous synthetic methodologies reported up to now, carbohelicenes and their
      derivatives can be tailor-made for a better involvement in several subfields.
      Among those domains are: nanosciences, chemosensing, liquid crystals, molecular
      switches, polymers, foldamers, supramolecular materials, molecular recognition,
      conductive and opto-electronic materials, nonlinear optics, chirality studies and
      asymmetric synthesis. Helicene chemistry is now at a developmental stage, where
      sufficient application data are now collected and are extremely useful. They
      provide many more ideas for setting up the basis for future innovative
      applications.

PMID- 23151679
TI  - Strong influence of variants near MC4R on adiposity in children and adults: a
      cross-sectional study in Indian population.
AB  - Common variants near melanocortin 4 receptor (MC4R) gene are shown to be
      associated with adiposity but have varied effects in different age groups. Among
      Indians, studies have shown association of these variants with obesity in adults,
      but their association in children is yet to be confirmed. We evaluated
      association of rs17782313 and rs12970134 near MC4R with adiposity and related
      traits in Indians including 1362 children and 4077 adults (consisting of 2049
      diabetic and 2028 nondiabetic adult subjects). Both variants rs17782313 and
      rs12970134 showed strong association with adiposity measures (weight, body mass
      index and waist circumference) in children (P-range 7.6 * 10(-5)-3.8 * 10(-12))
      and nominal association in nondiabetic adults (P-range 0.05-0.003). Effect sizes
      on adiposity measures in children (beta range 0.22-0.26 Z-score) were ~3-fold
      higher compared with adults (beta range 0.06-0.08). The minor alleles of both
      variants showed borderline association (P-range 0.08-0.04) with risk of type 2
      diabetes in adults. Meta-analysis of rs12970134 in >12 000 Indian adults
      corroborated its association with adiposity (P<=2.2 * 10(-9)), homeostasis model
      assessment-estimated insulin resistance (P=4.0 * 10(-5)) and type 2 diabetes
      (P=0.003) with only moderate heterogeneity, suggesting similar effect on adult
      Indians residing in different geographical regions. In conclusion, the study
      demonstrates association of variants near MC4R with obesity and related traits in
      Indian children and adults, with higher impact during childhood.

PMID- 23151681
TI  - Stereotactic radiosurgery for the treatment of melanoma and renal cell carcinoma
      brain metastases.
AB  - Renal cell carcinoma (RCC) and melanoma brain metastases have traditionally been
      considered radioresistant lesions when treated with conventional radiotherapeutic
      modalities. Radiosurgery provides high-dose radiation to a defined target volume
      with steep fall off in dose at lesion margins. Recent evidence suggests that
      stereotactic radiosurgery (SRS) is effective in improving local control and
      overall survival for a number of tumor subtypes including RCC and melanoma brain
      metastases. The purpose of this study was to compare the response rate to SRS
      between RCC and melanoma patients and to identify predictors of response to SRS
      for these 2 specific subtypes of brain metastases. We retrospectively reviewed a
      prospectively maintained database of all brain metastases treated with Gamma
      Knife SRS at the University Health Network (Toronto, Ontario) between October
      2007 and June 2010, studying RCC and melanoma patients. Demographics, treatment
      history and dosimetry data were collected; and MRIs were reviewed for treatment
      response. Log rank, Cox proportional hazard ratio and Kaplan-Meier survival
      analysis using SPSS were performed. A total of 103 brain metastases patients (41
      RCC; 62 melanoma) were included in the study. The median age, Karnofsky
      performance status score and Eastern Cooperative Oncology Group performance score
      was 52 years (range 27-81), 90 (range 70-100) and 1 (range 0-2), respectively.
      Thirty-four lesions received adjuvant chemotherapy and 56 received pre-SRS whole
      brain radiation therapy. The median follow-up, prescription dose, Radiation
      Therapy Oncology Group conformity index, target volume and number of shots was 6
      months (range 1-41 months), 21 Gy (range 15-25 Gy), 1.93 (range 1.04-9.76), 0.4
      cm3 (range 0.005-13.36 cm3) and 2 (range 1-22), respectively. Smaller tumor
      volume (P=0.007) and RCC pathology (P=0.04) were found to be positive predictors
      of response. Actuarial local control rate for RCC and melanoma combined was 89%
      at 6 months, 84% at 12 months, 76% at 18 months and 61% at 24 months. Local
      control at 12 months was 91 and 75% for RCC and melanoma, respectively. SRS is a
      valuable treatment option for local control of RCC and melanoma brain metastases.
      Smaller tumor volume and RCC pathology, predictors of response, suggest distinct
      differences in tumor biology and the extent of radioresponse between RCC and
      melanoma.

PMID- 23151682
TI  - Respiratory and sleep disorders in mucopolysaccharidosis.
AB  - MPS encompasses a group of rare lysosomal storage disorders that are associated
      with the accumulation of glycosaminoglycans (GAG) in organs and tissues. This
      accumulation can lead to the progressive development of a variety of clinical
      manifestations. Ear, nose, throat (ENT) and respiratory problems are very common
      in patients with MPS and are often among the first symptoms to appear. Typical
      features of MPS include upper and lower airway obstruction and restrictive
      pulmonary disease, which can lead to chronic rhinosinusitis or chronic ear
      infections, recurrent upper and lower respiratory tract infections, obstructive
      sleep apnoea, impaired exercise tolerance, and respiratory failure. This review
      provides a detailed overview of the ENT and respiratory manifestations that can
      occur in patients with MPS and discusses the issues related to their evaluation
      and management.

PMID- 23151683
TI  - Parental social support, coping strategies, resilience factors, stress, anxiety
      and depression levels in parents of children with MPS III (Sanfilippo syndrome)
      or children with intellectual disabilities (ID).
AB  - Mucopolysaccharidosis type III (MPS III, Sanfilippo syndrome) is a lysosomal
      storage disorder, caused by a deficiency in one of four enzymes involved in the
      catabolism of the glycosaminoglycan heparan sulphate. It is a degenerative
      disorder, with a progressive decline in children's intellectual and physical
      functioning. There is currently no cure for the disorder. To date there is a
      paucity of research on how this disorder impacts parents psychological
      functioning. Specifically, research in the area has failed to employ adequate
      control groups to assess if the impact of this disorder on parents psychological
      functioning differs from parenting a child with intellectual disability (ID). The
      current study examined child behaviour and parental psychological functioning in
      23 parents of children with MPS III and 23 parents of children with ID. Parents
      completed postal questionnaires about their child's behaviour and abilities and
      their own psychological functioning. Parents of children with MPS III reported
      fewer behavioural difficulties as their child aged, more severe level of
      intellectual disability, and similar levels of perceived social support, coping
      techniques, stress, anxiety and depression levels as parents of children with ID.
      Both groups of parents scored above the clinical cut off for anxiety and
      depression. Parents of children with MPS III rated themselves as significantly
      less future-orientated and goal directed than parents of children with ID.
      Services should develop support packages for parents of children with MPS III
      that incorporate an understanding of the unique stressors and current-difficulty
      approach of this population. Future research should examine gender differences
      between parental psychological functioning, using mixed qualitative and
      quantitative approaches, and utilise matched developmental level and typically
      developing control groups.

PMID- 23151685
TI  - Treatment of refractory obstetric antiphospholipid syndrome: the state of the art
      and new trends in the therapeutic management.
AB  - OBJECTIVE: To date, there are no reliable data regarding the actual treatment
      received by women with refractory obstetric antiphospholipid syndrome (OAPS). The
      aim of this study was to assess current clinical evidence and new trends in the
      treatment of refractory OAPS. METHODS: A non-systematic but comprehensive
      literature search using relevant keywords was made to identify relevant articles
      published in English from different computerized databases: PubMed (Medline),
      Google Scholar electronic database search and The Cochrane Library, from January
      2000 to March 2012. Studies on the treatment of poor obstetric outcomes in women
      with OAPS were included. Prospective randomized clinical trials, cohort studies,
      reviews, systematic reviews and meta-analysis were retrieved. RESULTS: A total of
      130 articles were finally selected for this review, including 17 randomized
      clinical trials and four meta-analyses. The majority of articles were non
      randomized original papers and basic and clinical reviews. CONCLUSION: Up to 20%
      of women with OAPS do not receive the currently recommended therapeutic regimen.
      Unfortunately, well-designed studies regarding the usefulness of new drugs in
      refractory OAPS are scarce. Hydroxychloroquine and low-dose prednisolone appear
      to be useful when added to standard therapy. Current data do not support the use
      of intravenous immunoglobulins in this field. The role played by double anti
      aggregant therapy, fondaparinux, vitamin D, pentoxifylline and TNF-targeted
      therapies should be tested in well-designed studies.

PMID- 23151684
TI  - Increased glucocerebrosidase (GBA) 2 activity in GBA1 deficient mice brains and
      in Gaucher leucocytes.
AB  - Lysosomal glucocerebrosidase (GBA1) deficiency is causative for Gaucher disease.
      Not all individuals with GBA1 mutations develop neurological involvement raising
      the possibility that other factors may provide compensatory protection. One
      factor may be the activity of the non-lysosomal beta-glucosidase (GBA2) which
      exhibits catalytic activity towards glucosylceramide and is reported to be highly
      expressed in brain tissue. Here, we assessed brain GBA2 enzymatic activity in
      wild type, heterozygote and GBA1 deficient mice. Additionally, we determined
      activity in leucocytes obtained from 13 patients with Gaucher disease, 10
      patients with enzymology consistent with heterozygote status and 19 controls. For
      wild type animals, GBA2 accounted for over 85 % of total brain GBA activity and
      was significantly elevated in GBA1 deficient mice when compared to heterozygote
      and wild types (GBA1 deficient; 92.4 +/- 5.6, heterozygote; 71.5 +/- 2.4, wild
      type 76.8 +/- 5.1 nmol/h/mg protein). For the patient samples, five Gaucher
      patients had GBA2 leucocyte activities markedly greater than controls. No
      difference in GBA2 activity was apparent between the control and carrier groups.
      Undetectable GBA2 activity was identified in four leucocyte preparations; one in
      the control group, two in the carrier group and one from the Gaucher disease
      group. Work is now required to ascertain whether GBA2 activity is a disease
      modifying factor in Gaucher disease and to identify the mechanism(s) responsible
      for triggering increased GBA2 activity in GBA1 deficiency states. 

PMID- 23151686
TI  - Grape seed extract as a potential remineralizing agent: a comparative in vitro
      study.
AB  - OBJECTIVE: Remineralization is an effective treatment that may stop or reverse
      early tooth decay. Grape seed extract (GSE) is the potential remineralizing agent
      under investigation. MATERIALS AND METHODS: Sound human tooth sections were
      obtained from the cervical portion of the root and stored in demineralizing
      solution at 37 degrees C for 96 hours to induce artificial root caries lesions.
      The sections were divided into four treatment groups including 6.5% grape seed
      extract, sodium monofluorophosphate (220 ppm) with 0.05% calcium
      glycerophosphate, 0.5% calcium glycerophosphate and control (no treatment). An in
      vitro pH cycling model was used to cycle the demineralized specimens through
      treatment solutions, acidic buffer and neutral buffer for 8 days at 6 cycles per
      day. Subsequently, they were evaluated using confocal laser scanning microscope.
      Data were analyzed using analysis of variance (p < 0.05). RESULTS: GSE revealed
      less demineralization and more remineralization compared with other groups.
      CONCLUSION: GSE promotes remineralization of artificial root caries lesions.
      CLINICAL SIGNIFICANCE: The search for the perfect remineralizing agent continues
      to this day. GSE could be a welcome addition to the remineralization
      armamentarium.

PMID- 23151687
TI  - Comparison of antimicrobial activities and compressive strength of alginate
      impression materials following disinfection procedure.
AB  - AIM: This study investigated the effectiveness of disinfecting solution when
      incorporated into alginate powder instead of water against some microorganisms
      and on compressive strength of alginate. MATERIALS AND METHODS: For measuring
      antimicrobial activity of alginate, 60 alginate specimens were prepared and
      divided into two groups: One with water incorporated in the mix (control) and the
      other with 0.2% chlorhexidine digluconate incorporated in the mix instead of
      water. The tested microorganisms were: gram +ve cocci, gram -ve bacilli and yeast
      (each group 10 samples). For measuring compressive strength, 20 specimens of
      alginate were divided into two groups: One with water incorporated in the mix
      (control) and the other with chlorhexidine incorporated in the mix. RESULTS: The
      statistical analysis of antimicrobial efficacy of alginate was performed with
      Mann-Whitney U-test, which revealed very high significant difference when
      comparing among groups (p < 0.000). Student t-test analyzed the compressive
      strength data which revealed nonsignificant difference between groups (p > 0.05).
      CONCLUSION: The incorporation of disinfecting agents into impression materials
      could serve an important role in dental laboratory infection control and it had
      no adverse effect on compressive strength of the hydrocolloid alginate. CLINICAL
      SIGNIFICANCE: The risk of transmitting pathogenic microorganisms to dental
      laboratories via impression has been considered a topic of importance for a
      number of years.

PMID- 23151688
TI  - Comparative study of the antimicrobial effect of three irrigant solutions
      (chlorhexidine, sodium hypochlorite and chlorhexidinated MUMS).
AB  - AIM: To compare the antimicrobial effect of 2% chlorhexidine, 2.5% sodium
      hypochlorite and MUMS containing 2% chlorhexidine. MATERIALS AND METHODS: All of
      the above irrigants were examined on Enterococcus faecalis, Streptococcus mutans,
      Candida albicans, Lactobacillus casei and E. coli. A total of 0.5 CC of each
      solution and 0.5 CC of McFarland solution bacterium were added to each
      examination tube. After 15, 30 and 45 minutes, colony count was performed for
      each tube. The difference in the number of bacteria indicated the effect taken by
      disinfectant material. RESULTS: MUMS containing chlorhexidine showed the
      antimicrobial properties just like chlorhexidine's effect against E. coli,
      Streptococcus mutans, Candida albicans, Enterococcus faecalis and Lactobacillus
      casei in preventing these entire microorganisms to incubate. Sodium hypochlorite
      was not effective against Enterococcus faecalis and Candida albicans incubated in
      15, 30 and 45 minutes and Enterococcus faecalis in 15 minutes. CONCLUSION: MUMS
      has antimicrobial properties similar to chlorhexidine. CLINICAL SIGNIFICANCE: As
      MUMS containing chlorhexidine can transfer chlorhexidine through its own
      surfactant around apical area and it can open the dentinal tubules by its own
      chelator for more penetration of chlorhexidine, it may be a choice for canal
      irrigation.

PMID- 23151689
TI  - Dynamic model of hydrogen peroxide diffusion kinetics into the pulp cavity.
AB  - AIM: To measure the time course hydrogen peroxide penetration into the pulp
      cavity and evaluate short-term tooth color changes after bleaching. MATERIALS AND
      METHODS: Twenty extracted human canines were sectioned, pulp tissue removed and
      the cavity enlarged. Teeth were painted with nail varnish to leave a 6-mm
      diameter circle on the buccal surface. Baseline color was measured
      spectrophotometrically. Teeth were randomized into a control group (n = 10)
      treated with 30 ul of glycerin base and a bleaching group (n = 10) exposed to 30
      ul of 40% hydrogen peroxide for 1 hour. A linear low density polyethylene wrap
      was placed to prevent evaporation of the material. Acetate buffer was placed into
      the cavity and replenished every 10 minutes and placed into plastic tubes.
      Hydrogen peroxide amount was estimated spectrophotometrically using leukocrystal
      violet and horseradish peroxidase. Specimen color was remeasured immediately
      after bleaching, 1 hour, 1 day 1, 2 and 6 weeks postbleaching. Color change was
      measured per Commission Internationale de l'Eclairage methodology. Mann-Whitney
      procedure was used to assess baseline color measurements and total hydrogen
      peroxide penetration amount. Friedman's test was used to assess within group
      differences for color change and hydrogen peroxide penetration. RESULTS: There
      was significantly greater hydrogen peroxide penetration in the bleaching group (p
      < 0.05). Hydrogen peroxide penetration levels were constant throughout the 1-hour
      evaluation period in the bleaching group. The groups showed no difference at
      baseline with respect to any of L*a*b color measurements (p > 0.05). The
      postbleaching color measurement showed an increase of change in overall color
      (DeltaE) and lightness (DeltaL) up to 1 week followed by a gradual stabilization
      up to 6 weeks. CONCLUSION: This dynamic model provided information about the time
      course diffusion kinetics into the pulp cavity, demonstrating constant
      penetration of hydrogen peroxide into the pulp cavity during a 1-hour bleaching
      session. CLINICAL SIGNIFICANCE: A prolonged application of 40% hydrogen peroxide
      bleaching material for 1 hour produces constant penetration of hydrogen peroxide
      into the pulp cavity in vitro.

PMID- 23151690
TI  - Effects of citric acid and EDTA on periodontally involved root surfaces: a SEM
      study.
AB  - AIM: Root debridement by scaling and root planing may not completely remove
      contaminated cementum particularly in more apical areas. The smear layer formed
      during root planing inhibits cell migration and attachment leading to impaired
      marginal periodontal healing. The present study was done to compare the
      morphological effects of root surface demineralization using citric acid and EDTA
      as root-conditioning agents. MATERIALS AND METHODS: Thirty fragments of human
      dental roots previously exposed to periodontal disease were scaled and randomly
      divided into the following groups of treatment: Group I: Hand instrumentation and
      conditioning with normal saline for 5 minutes as control; group II: Hand
      instrumentation and conditioning with citric acid (pH 1) for 5 minutes and group
      III: Hand instrumentation and conditioning with EDTA (pH-7.4) for 5 minutes.
      Scanning electron microscopy was used to check for the presence of residual smear
      layer and for measuring the number and area of exposed dentin tubules. RESULTS:
      The mean efficacy of smear layer removal was compared between groups I and II,
      groups I and III and groups II and III, it was found to be statistically
      significant at 5%. When the mean diameter of the dentinal tubules and mean total
      surface area occupied by the dentinal tubule orifices was compared between groups
      II and III it was found to be statistically significant at 1% level of
      significance. CONCLUSION: Citric acid causes greater degree of morphological
      alterations than EDTA and is considered to be a better root-conditioning agent.
      However, the use of EDTA cannot be ruled out. CLINICAL SIGNIFICANCE: This study
      supports the hypothesis that demineralizing agents can be used as an adjunct to
      the periodontal treatment aiming at restoring the biocompatibility of roots and
      helps in choosing an appropriate agent for root conditioning.

PMID- 23151691
TI  - In vitro caries-preventive effect of fluoridated orthodontic resins against
      cariogenic challenge stimulation.
AB  - AIM: The aim of the present study was to evaluate the in vitro caries preventive
      effect of fluoridated orthodontic resins under pH cycling with two types of acid
      demineralizing saliva. MATERIALS AND METHODS: Brackets were bonded to 120
      extracted human premolars, using Rely-a-bond (n = 40), Tru- Bond (n = 40) and
      Ortho-one (n = 40) orthodontic bonding agents. Each group of resin was divided
      into 2 subgroups (n = 20): immersion in remineralizing artificial saliva for 14
      days and acid saliva with pH 4.3. After 14 days of pH cycling the caries
      preventive effect on the development of white spot lesion was evaluated
      considering the presence of inhibition zones to white spot lesions using two
      scores: 0 = absence and 1 = presence. Kruskal-Wallis ANOVA and Mann-Whitney U
      tests were used. RESULTS: Formation of white spot lesions was observed only under
      pH cycling using acid saliva with pH 4.3; with Rely-a-bond and Tru-Bond being
      significantly more effective in preventing the appearance of white spot lesions
      effect than Ortho-one. CONCLUSION: The acidity of the demineralizing solution
      influenced the formation of white spot lesions around orthodontic brackets under
      highly cariogenic conditions. Rely-a-bond and Tru-bond presented higher caries
      preventive effect than Orthoone. CLINICAL SIGNIFICANCE: The development of
      fluoride-containing materials cannot be regarded as a permanent means to control
      dental caries lesions, but a complement along with other preventive methods.

PMID- 23151692
TI  - Microbial colonization and their relation with potential cofactors in patients
      with denture stomatitis.
AB  - AIM: To determine microbial prevalence in the mucous membrane and prosthesis of
      denture wearers with and without denture stomatitis and to study its relationship
      with potential clinical cofactors. MATERIALS AND METHODS: Saliva was collected
      from 200 patients (100 female and 100 male) wearing dental prosthesis for
      measurement of pH. Oral samples of the mucous membrane and of dentures were taken
      with sterile swab for microbiological analysis. Medical and dietary history of
      the subjects was recorded. Chi-square test and analysis of varience were used for
      statistical analysis. RESULTS: Diabetes, hypertension and high carbohydrate
      ingestion was observed in majority of patients. The pH average in saliva was of
      5.1. The presence of C. albicans, S. aureus and S. mutans in the mucous membrane
      was of 55.4, 56.4 and 63.6% respectively. C. albicans was isolated in 69.7% from
      the prosthesis, whereas S. aureus and S. mutans were isolated in 45.3%. The
      isolation of C.albicans was more frequent in patients with denture stomatitis.
      CONCLUSION: C. albicans, S. aureus and S. mutans frequently colonize the oral
      mucous of denture wearers. This is more frequently observed in patients with
      denture stomatitis. CLINICAL SIGNIFICANCE: Denture stomatitis is associated to
      Candida albicans, different bacteria and other cofactors, such as salivary pH,
      carbohydrate ingestion, systemic illnesses and medication.

PMID- 23151693
TI  - Comparing the effect of different mouthrinses on de novo plaque formation.
AB  - PURPOSE: Several antiplaque agents are being available in the market in spite of
      vast development of modern medical science, satisfactory treatment of 'oral
      diseases' by newer drugs is not fully achieved, rather the chemical compounds has
      exposed the patients to it is different ill effects, therefore, there is interest
      to find out effective remedy of any disease by harmless herbal drugs thus the aim
      of this study was to compare plaque formation at 24 hours after the use of
      Triphala, Hi ora, Chlorhexidine and Colgate Plax mouth washes. METHODS: A
      controlled, randomized, double-blind, crossover clinical trial was designed.
      Thirty subjects underwent four consecutive experimental phases with four
      treatments: Triphala, Hi Ora, Chlorhexidine and Colgate Plax. On the day of
      study, the subjects discontinued all other oral hygiene habits and were randomly
      assigned for treatment with the experimental mouthwash. Each experimental phase
      was preceded by a 28-day washout period. Plaque formation was recorded after one
      undisturbed day. RESULTS: Triphala, Hi Ora and Chlorhexidine reduced de novo
      plaque formation to a greater extent than the colgate plax mouthwash (p < 0.05).
      CONCLUSION: Triphala and Hi Ora presents an anti-plaque efficacy similar to that
      of chlorhexdine, and was more effective at inhibiting plaque formation than the
      Colgate Plax mouth wash.

PMID- 23151694
TI  - Comparison of chemical aging and water immersion time on durability of resin
      dentin interface produced by an etch-and-rinse adhesive.
AB  - AIM: The aim of this study was to analyze and compare the influence of short-term
      NaOCl-storage and long-term water storage on the microtensile bond strength
      (uTBS) of etch-and-rinse adhesive system to human dentin. MATERIALS AND METHODS:
      Thirty-six third human molars were randomly divided into 6 groups (n = 6)
      according to the aging protocol: G1 (water, 24 hours); G2 (water, 6 months); G3
      (water, 12 months); G4 (10% sodium hypochlorite--NaOCl, 1 hour); G5 (10% NaOCl, 3
      hours) and G6 (10% NaOCl, 5 hours). A two-step etch-and-rinse adhesive (Adper
      Single Bond 2) was applied according to the manufacturers' instructions. A
      composite (Filtek Z250) was applied in four horizontal increments and was
      individually cured. Specimens were cut following the microtensile test technique,
      submitted to the different aging protocols, and tested in tension. The fracture
      pattern was observed in a stereomicroscope (40* magnification) and in a scanning
      electron microscope. The uTBS data were analyzed by ANOVA and Tukey's test (alpha
      = 0.05). RESULTS: The effect of storage in 10% NaOCl for 1 or 3 hours was not
      significantly different from that of aging in distilled water (DW) for 6 or 12
      months (p > 0.05). Beams immersed in DW for 24 hours and in 10% NaOCl for 5 hours
      showed the highest and lowest uTBS values respectively. CONCLUSION: The aging
      protocols negatively influenced dentin bond strength. Aging specimens in 10%
      NaOCl for 1 or 3 hours can be an alternative method for long-term water storage
      (6 or 12 months) bond strength studies. CLINICAL SIGNIFICANCE: This aging
      protocol allows a quick achievement of longitudinal bond strength data, so that
      results are available to the professionals in this area while the materials are
      yet present at the dental market.

PMID- 23151695
TI  - The effect of different curing time regimens on immediate postpolymerization
      color changes of resin composites.
AB  - AIM: Light curing of resin composites may considerably change the color of resin
      composites. The aim of this study was to evaluate the changing pattern of resin
      composite's color by different curing times. MATERIALS AND METHODS: Fifteen, 1 mm
      thick, samples of each A2 shade Clearfill and Filtek P60 composites were
      prepared. First five samples were cured for 10s (400 mW/cm2) in each pole of the
      rectangular samples (right upper, right lower, left lower, left upper plus
      central zone). Consecutive sets of samples, each consists of five, were
      irradiated by doubling and tripling the curing time to 20 and 30s. Color change
      were measured by means of CIE 1976 L*a*b system equation (DeltaE) for each
      digitalized picture of the corresponding sample. RESULTS: Color of samples was
      clinically significant changed by increasing the curing time from 10 to 20s and
      from 20 to 30s for Clearfil (DeltaE = 13.86 and 14.11 respectively,) and Filtek
      P60 (DeltaE = 7.68 and 11.66 respectively). The 'b' component change was
      responsible for the most color alteration confirmed by the linear regression
      model (p < 0.001). CONCLUSION: This study revealed the contrasting pattern of
      resin composite's color change with the different curing times. Our findings
      support that light curing is accompanied by a higher attained blue chroma and
      diminished yellowness of resin composites. CLINICAL SIGNIFICANCE: A complete and
      proper curing of sample resin composites on buccal surface of particular tooth,
      as a common practice to ensure the maximize concordance composite and tooth
      color, is reassured according to the considerable differences of undercured and
      overcured in comparison to normocured composite.

PMID- 23151696
TI  - Mechanical properties of cast commercially pure titanium simulating ceramic
      firing cycles.
AB  - AIM: To evaluate the mechanical properties (ultimate tensile strength, elongation
      and hardness) of the commercially pure titanium (cp Ti) as casting and after
      ceramic firing cycles. MATERIALS AND METHODS: Dumbbell-shaped specimens were
      prepared for the tensile strength testing. Disk-shaped cast specimens were used
      for microhardness testing. The ceramic firing cycles were made simulating a low
      fusion ceramic application. Tensile testing was conducted in a universal testing
      machine at a crosshead speed of 1 mm/min until failure. Ultimate tensile strength
      and elongation were recorded. The fracture mode was analyzed by scanning electron
      microscopy. Vickers hardness was measured in a hardness tester. The data from the
      tensile and hardness tests were subjected to a one-way analysis of variance and
      Tukey's test (alpha = 0.05). RESULTS: The mean values of tensile strength were
      not changed by the ceramic firing cycles. Lower hardness was observed for cp Ti
      as casting compared with Ti cast after the firing cycles. CLINICAL SIGNIFICANCE:
      The ceramic firing cycles did not show any considerable prejudicial effects on
      the mechanical properties of the cp Ti.

PMID- 23151697
TI  - Comparative analysis for selection of resin luting cements based on filler
      content: an in vitro study.
AB  - CONTEXT: Resin luting of all-ceramic restorations results in increased
      performance; however, the strengthening mechanism and the role of the mechanical
      properties of the resin are not fully understood. OBJECTIVE: The aim of this
      study was to investigate the effect of filler content on the flexural properties
      of resin luting agents and thereby selecting an appropriate resin luting cement.
      MATERIALS AND METHODS: Three esthetic resin luting agents studied were Calibra
      (Dentsply); RelyX ARC and Panavia F. Ten beam-shaped specimen (L * W * H: 30 * 8
      * 2 mm) were made for each of the material tests carried out. The specimens were
      stored in distilled water for 24 hours at 37 degrees C. The specimens were then
      tested for flexural strength (MPa) and flexural modulus (GPa) using the three
      point bending method on a universal material testing machine at a cross head
      speed of 0.5 mm/min. Data obtained were statistically analyzed using ANOVA
      followed by post-hoc-Tukey's test with p < 0.05 for statistical significance.
      RESULTS: Increase in mean strength related to an associated increase in the
      elastic modulus which in turn was related to the filler loading of the resin
      luting cements. CONCLUSION: Strength and performance of resin-cemented allceramic
      restoration can be enhanced by the use of a resin luting cement having increased
      filler content. CLINICAL IMPLICATIONS: Resin-composite cements may be most
      suitable for adhesively bonded restorations, where margins are placed on
      supragingival enamel, and where ultimate strength and energy absorption are
      paramount. The selection criteria for a resin cement depends on its flexural
      strength. To a great extent, the flexural strength is dependent on the filler
      loading of the resin luting cement.

PMID- 23151698
TI  - Comparison of shear bond strength of metal brackets bonded to porcelain surface
      using different surface conditioning methods: an in vitro study.
AB  - AIM: To evaluate and compare the shear bond strength of metal brackets bonded to
      ceramic surfaces using different conditioning methods and to assess the site of
      bond failure after debonding. MATERIALS AND METHODS: A total of 70 ceramic
      surfaces were produced with uniform shape, size and composition. The samples were
      divided into 7 groups (each of 10 samples). Group 1 was the control group
      (untreated surface); in group 2 the surface were roughened with a diamond bur; in
      group 3 the surface were etched with hydrofluoric acid; in group 4 the surfaces
      were sandblasted; in group 5 the surfaces roughened with bur and silane applied;
      in group 6 the surfaces were etched with hydrofluoric acid and silane applied and
      in group 7 the surfaces were sandblasted and silane applied. To all the above
      groups, metal orthodontic brackets were bonded with light cure adhesive. The
      brackets were later stored in artificial saliva and incubated at 37 degrees C (24
      hours). The samples were then subjected to shear bond strength test using an
      Instron universal testing machine. The debonded porcelain surfaces were then
      studied under stereomicroscope to assess site of bond failure. RESULTS:
      Sandblasting the ceramic surface and silane application showed the highest bond
      strength. Stereomicroscope examination after debonding showed that the bond
      failure is at bracket-adhesive interface in four groups namely hydrofluoric acid,
      sandblasting, hydrofluoric acid with silane and sandblasting with silane.
      CONCLUSION: Sandblasting with silane combination produced the highest shear bond
      strength, so it is a clinically suitable method for bonding orthodontic metal
      brackets onto ceramic surface. CLINICAL RELEVANCE: Bonding orthodontic brackets
      to ceramic crowns of patients has been a tough task. In this study, different
      conditioning methods were used to treat the ceramic surfaces before bonding. The
      results showed that sandblasting the ceramic surface prior to application of
      silane produced the highest shear bond strength which is clinically suitable to
      reduce bond failures.

PMID- 23151699
TI  - Comparison of Opal self-ligating brackets with manually ligating brackets.
AB  - This study was conducted with aim to evaluate the efficiency of the newly
      introduced Opal self-ligating brackets (SLB). The chairside time saved, appliance
      efficiency, bracket bond failures, breakages and bracket staining in the Opal
      SLBs were compared with the conventional standard metal manually ligating
      brackets (MLBs) of MBT system. Seven patients were compared in each group.
      Standard light curing bonding methods were used in both the group. Chairside time
      saving, appliance efficiency and bracket bond failures were compared among the
      groups whereas staining was observed with the SLBs. Appliance efficiency was
      evaluated by PAR scores. Results showed significant chairside time being saved in
      SLBs, whereas the appliance efficiency was not significant. Bond failures were
      found only in SLBs as well as breakages along with staining. Henceforth, we could
      conclude that though SLBs had advantage of saving chairside time but also had
      disadvantage of losing more time with bond failures.

PMID- 23151700
TI  - Evaluation of the Cadiax Compact(r) II accuracy in recording preadjusted condylar
      inclinations on fully adjustable articulator.
AB  - BACKGROUND: Mandibular movement analysis is a critical step in making the
      functional occlusal morphology and improving the diagnosis and treatment of
      temporomandibular joint disorders (TMDs). Cadiax Compact(r) is an electronic
      condylograph that claims to record the horizontal condylar inclination (HCI),
      Bennett angle (BA) and relative shape of the articular eminence. This study aims
      at assessing the accuracy of Cadiax Compact(r) II in its claimed abilities.
      MATERIALS AND METHODS: The electronic condylograph (Cadiax Compact(r)II) was
      fitted on the fully adjustable articulator (gamma dental reference-SL). After
      setting of HCI and BA on the arbitrary degrees, eccentric movements were produced
      manually on the articulator. The Cadiax recorded these preadjusted angles and the
      accuracy of its recordings was assessed by comparison of the results with the
      preadjusted HCI, BA and color inserts as references. RESULTS: The majority of the
      comparisons showed statistically significant differences between articulator
      settings and Cadiax recordings. However, the maximum difference was about 2.50
      which seems acceptable for clinical practice. CONCLUSION: The obtained results
      showed that Cadiax Compact is an accurate and reliable instrument for diagnostic
      purposes, yielding reproducible measurements. Despite this, Cadiax is a
      technically sensitive device that can preclude its routine usage.

PMID- 23151701
TI  - A clinicopathological study of ossifying fibromas and comparison between central
      and peripheral ossifying fibromas.
AB  - AIMS AND OBJECTIVES: To study the clinical, histological features of peripheral
      and central ossifying fibromas and also to compare between them. MATERIALS AND
      METHODS: The sample comprised a total 50 cases of ossifying fibromas [25 central
      ossifying fibromas (COF) and 25 peripheral ossifying fibromas (POF)] inclusive of
      cemento-ossifying fibromas. RESULTS: The mean age is 28.2 years in POF and 24.7
      years in COF. The male: female ratio was 1:1.5 in POF and 1:1.8 in COF. The size
      of the lesions varied from 0.45 to 2.75 cm in cases of POF and in COF, it ranged
      from 1.25 to 13.5 cm. COF showed more duration (1-8 years) when compared with POF
      (1-3). Majority of cases of COF showed radiolucent, mixed radiolucent and
      radiopaque unilocular lesions. The predominant cell type in both POF and COF was
      a combination of both ovoid and spindle cells. Regarding vascularity it showed
      mild, moderate and intense vascularity. On comparison of all stromal changes
      between POF and COF showed no statistically significant difference. CONCLUSION:
      The clinical parameters and radiographic changes of POF and COF in our study were
      similar to the previous studies. Histopathological features like type of cells,
      cellularity and vascularity in POF and COF were similar to previous studies.
      However, when clinical and histopathological features were compared between POF
      and COF showed no statistical significance except for site of the lesion. These
      features signify the behavior of two lesions. Further research on larger sample
      might give more insights into these lesions.

PMID- 23151702
TI  - A comparative evaluation of DIAGNOdent and caries detector dye in detection of
      residual caries in prepared cavities.
AB  - AIM: The objective of this study was to determine the association between
      DIAGNOdent laser and caries detector dye in detection of the remaining caries in
      restorative cavities. MATERIALS AND METHODS: The sample consisted of 100 cavities
      prepared in patients referring to the Department of Restorative Dentistry of
      Mashhad Dental School. After confirming caries absence by tactile examination,
      the presence of any residual caries was determined by a laser fluorescence (LF)
      device (DIAGNOdent Pen) and then by caries detector dye. The data were analyzed
      through McNemar test. RESULTS: When the cut off value was considered as >=13,
      both DIAGNOdent Pen and caries detector dye found 54 cavities as without caries
      and 12 cavities as carious. There were 32 teeth diagnosed as decayed only by the
      dye and two cases that were diagnosed as having residual caries only by the
      DIAGNOdent. The McNemar test revealed a significant difference in the diagnosis
      of residual caries between the two methods (p < 0.05), as well as significant
      differences between each method and tactile examination (p < 0.05). When the cut
      off value was set at >=25, no significant difference was found between laser
      fluorescence and tactile examination in residual caries detection (p > 0.05).
      CONCLUSION: Both DIAGNOdent Pen and caries detector dye can be considered as
      adjuncts for detecting residual caries in prepared cavities. However, the use of
      laser fluorescence device can provide results that are more consistent with
      tactile examination, while relying on caries detector dye may result in excessive
      removal of tooth tissue, and thus increase the risk of pulpal exposure. CLINICAL
      SIGNIFICANCE: Incomparision with caries detector dye, Residual caries detection
      by DIAGNOdent Pen is more consistent with tactile examination.

PMID- 23151703
TI  - Clinical and histological comparison of polyglycolic acid suture with black silk
      suture after minor oral surgical procedure.
AB  - Any suture material, absorbable or nonabsorbable, elicits a kind of inflammatory
      reaction within the tissue. Nonabsorbable black silk suture and absorbable
      polyglycolic acid suture were compared clinically and histologically on various
      parameters. MATERIALS AND METHODS: This study consisted of 50 patients requiring
      minor surgical procedure, who were referred to the Department of Oral and
      Maxillofacial Surgery. Patients were selected randomly and sutures were placed in
      the oral cavity 7 days preoperatively. Polyglycolic acid was placed on one side
      and black silk suture material on the other. Seven days later, prior to surgical
      procedure the sutures will be assessed. After the surgical procedure the sutures
      will be placed postoperatively in the same way for 7 days, after which the
      sutures will be assessed clinically and histologically. RESULTS: The results of
      this study showed that all the sutures were retained in case of polyglycolic acid
      suture whereas four cases were not retained in case of black silk suture. As far
      as polyglycolic acid suture is concerned 25 cases were mild, 18 cases moderate
      and seven cases were severe. Black silk showed 20 mild cases, 21 moderate cases
      and six severe cases. The histological results showed that 33 cases showed mild,
      14 cases moderate and three cases severe in case of polyglycolic acid suture.
      Whereas in case of black silk suture 41 cases were mild. Seven cases were
      moderate and two cases were severe. Black silk showed milder response than
      polyglycolic acid suture histologically. CONCLUSION: The polyglycolic acid suture
      was more superior because in all 50 patients the suture was retained. It had less
      tissue reaction, better handling characteristics and knotting capacity.

PMID- 23151704
TI  - Association of temporomandibular joint dysfunction, condylar position and dental
      malocclusions in Davangere population.
AB  - AIMS: To study the association between dental malocclusions and temporomandibular
      joint dysfunction.To study the association between dental malocclusions and
      condylar position.To study the association between temporomandibular (TM) joint
      dysfunction and condylar position. METHODS: The subjects were divided into four
      groups for dental malocclusions viz. class I malocclusion with or without TM
      dysfunction, class II division 1 malocclusion with or without TM dysfunction,
      class II division 2 malocclusion with or without TM dysfunction and class III
      malocclusion with or without TM dysfunction. Once the patient fulfilled the
      criteria, the presence or absence of signs of TM dysfunction were elicited from
      the patient. RESULTS: It shows the association between TM dysfunction signs and
      left and right condylar positions. It shows the association between TM
      dysfunction symptom and left and right condylar positions. It shows the
      association between dental malocclusions and TM dysfunction signs and symptom. It
      shows the association between dental malocclusions and left and right condylar
      positions. CONCLUSION: There was an association between TM dysfunction signs and
      left and right condylar positions. But, there was no association between TM
      dysfunction symptoms and left and right condylar positions. There was an
      association between dental malocclusions and TM dysfunction signs. But there was
      no association between dental malocclusions and TM dysfunction symptoms. There
      was an association between dental malocclusions and left condylar position, but
      there was no association between dental malocclusion and right condylar position.
      CLINICAL SIGNIFICANCE: This study indicates that malocclusions and factors of
      condylar position should be seen as merely cofactors in the sense of one piece of
      the mosaic in the multifactorial problem of TM dysfunction. TM dysfunction
      factors that showed significant effects to various malocclusions through this
      study . This study shows clinical significance of association of various types of
      dental malocclusions to different conylar positions and TM dysfunction signs and
      symptoms. Before treating orthodontic patients, one should evaluate and treat the
      TM disorders for better prognosis.

PMID- 23151705
TI  - Assessment of maximum voluntary bite force in adults with normal occlusion and
      different types of malocclusions.
AB  - AIM: Maximum voluntary bite force (MVBF) was assessed in adults with class I
      normal occlusion and compared with different malocclusions. MATERIALS AND
      METHODS: One hundred and ten subjects in the age group of 17 to 25 years were
      classified into various groups. Thirty subjects with class I normal occlusion
      (Group A), 20 subjects with Angle's class I malocclusion (Group B), 20 subjects
      with skeletal class II malocclusion (Group C), 20 subjects with hypodivergent
      facial morphology (Group D) and 20 subjects with hyperdivergent facial morphology
      (Group E). MVBF was measured with a bite force meter at the first premolar and
      first molar region bilaterally. The values were recorded and statistically
      analyzed. RESULTS: Mean MVBF value in each of the groups in the molar and first
      premolar region were found to be 601.83N +/- 60.80, 392N +/- 31.43 (group A),
      592.60N +/- 37.66, 378.90N +/- 23.00 (group B), 586.60N +/- 49.26, 377N +/- 29.38
      (group C), 771.50N +/- 27.24, 500.60N +/- 18.25 (group D), 283.85N +/- 26.41,
      283.85N +/- 26.41 (group E). Student paired t-test was done to analyze the
      difference between two groups and considered as significant at a p-value of <
      0.05. Significant difference was found between group A and D and group A and E
      with a p-value of <0.0001. No significant difference was observed between group A
      and group B (p = 0.5481 and 0.1148) and group A and group C (p = 0.3551 and
      0.0949). ANOVA showed that there was a significant difference among groups A, D
      and E. No significant difference was found among groups A, B and C. Males had a
      higher value than females. CONCLUSION: Sagittal morphology does not significantly
      affect the MVBF value whereas there is a significant correlation with vertical
      morphology. CLINICAL SIGNIFICANCE: Assessment of maximum voluntary bite force
      (MVBF) is a chairside procedure to evaluate masticatory muscle activity based on
      which treatment planning and mechanics can be known.

PMID- 23151706
TI  - Maxillomandibular plane angle bisector (MM) adjunctive to occlusal plane to
      evaluate anteroposterior measurement of dental base.
AB  - AIM: This study was undertaken to analyze the clinical usefulness of the
      maxillomandibular bisector, its reproducibility, its validity and its
      relationship to the functional occlusal plane, the bisecting occlusal plane and
      the nature of its cant. MATERIALS AND METHODS: Thirty pretreatment lateral
      cephalograms, each of adolescents (above 18 years of age) and children (10- 12
      years), seeking orthodontic treatment were randomly selected and the Wits
      technique of anteroposterior measurement was used to compare A-B values measured
      to the new plane with those measured to the functional occlusal plane (FOP) and
      to the traditional or bisecting occlusal plane (BOP). RESULTS: Present study
      showed that MM bisector plane is more reproducible and valid reference plane,
      than the FOP and BOP. CONCLUSION: A new plane, geometrically derived from the
      dental base planes, has been tested as an occlusal plane substitute for the
      measurement of anteroposterior jaw relationships. It lies close to but at an
      angle and inferior to the traditional occlusal planes and is highly reproducible
      at all times. CLINICAL SIGNIFICANCE: Maxillomandibular planes angle bisector may
      be a useful adjunct for the cephalometric assessment of sagittal relationship of
      the patient.

PMID- 23151707
TI  - Diagnostic reliability of fine needle aspiration cytology against histopathology
      for the diagnosis of oral squamous cell carcinoma and oral leukoplakia.
AB  - AIM: The purpose of this study was to determine the possibility of using fine
      needle aspiration cytology (FNAC) as a primary diagnostic test in oral
      leukoplakia and squamous cell carcinoma. MATERIALS AND METHODS: This study
      consisted of clinically diagnosed 15 cases of leukoplakia and 15 cases of oral
      squamous cell carcinomas. FNAC and biopsy were done on all the cases. A
      cytological and histopathological correlation was undertaken to determine the
      proportion of cancers. A 23-gauge sterile disposable needle was attached to a
      disposable syringe and introduced into the lesion at the proposed biopsy site in
      one movement. In leukoplakias, the center of the lesion or erythroplakic areas
      and, in squamous cell carcinomas, proliferative areas and edges of the ulcers
      were chosen. RESULTS: In leukoplakia group, out of 15 biopsy samples, one (6.67%)
      sample was negative and 14 (93.33%) were positive. Whereas out of 15 FNAC
      samples, 14 (93.33%) were negative and one (6.67%) sample was positive. In
      squamous cell carcinoma, out of 15 biopsy samples, no sample was negative and all
      (100.00%) were positive. Whereas out of 15 FNAC samples, two (13.33%) were
      negative and 13 (86.67%) sample were positive. CONCLUSION: It is noted that FNAC
      can be employed as a sound diagnostic tool for rapid diagnosis of oral squamous
      cell carcinoma. It may be particularly useful in cases, where formal biopsy
      procedure is difficult or contraindicated due to medical reasons or in cases of
      advanced malignancy. CLINICAL SIGNIFICANCE: FNAC has been shown to be reliable
      and safe technique in the diagnosis of malignant in the head and neck. When the
      aspirations are performed by cytopathologists, it is easy to perform a rapid
      staining of the first smear and within 10 to 15 minutes to ensure that the
      material is sufficient and diagnosable and to suggest a preliminary diagnosis.

PMID- 23151708
TI  - Comparison of working length determination using apex locator, conventional
      radiography and radiovisiography: an in vitro study.
AB  - AIM: The purpose of this study was to compare the working length determination
      done using three methods, namely, apex locator (Foramatron D-10, Parkell),
      radiovisiography (Planmeca) and conventional radiography (Prostyle intra,
      Planmeca). MATERIALS AND METHODS: In this experiment, to determine the working
      length, 35 single-rooted teeth were selected and each tooth was subjected to all
      the three methods of the working length determination. This was compared with the
      actual working length measured utilizing ground sections of the individual teeth.
      RESULTS: The results revealed that all the three methods located the apex nearly
      as accurately as the actual root canal length obtained by histological ground
      sectioning, and among three methods apex locator being the closest to the actual
      root canal length. CONCLUSION: The study concludes that all the three techniques
      are equally effective in determining working length.

PMID- 23151709
TI  - The influence of cervical preflaring of root canal on determination of initial
      apical file using Gates Glidden drills, Protaper, Race and diamond-coated Galaxy
      files.
AB  - AIM: To investigate the influence of cervical preflaring on apical file size
      determination using four different rotary instruments. MATERIALS AND METHODS:
      Fifty root canals from extracted human maxillary premolars with complete root
      formation, straight roots were used for the study. Access opening was done and
      the working length established with 8 no K-file for each canal. Teeth were
      randomly divided into five groups of 10 canals. In Group 1--no preflaring was
      done and acted as control and in Groups 2, 3, 4 and 5 cervical and middle third
      preflaring of the root canals were done using Gates Glidden drills, Protaper
      instruments, Race instruments and Galaxy files respectively. After preflaring,
      the apical file size determination was done and the initial apical file (IAF) was
      fixed at the working length. Teeth were sectioned transversally 1 mm from the
      apex, with the binding file in position. The samples were imaged under
      stereomicroscope with 30* magnification. Root canal and file maximum diameters
      were recorded for each sample. The readings were subjected to analysis of
      variance test and Scheffe's multiple comparison test. RESULTS: Preflaring with
      Race instruments lead to most accurate determination of the IAF. It was followed
      by Protaper, Galaxy files and Gates Glidden drills. CONCLUSION: Traditional
      method of apical size determination may lead to a substantial underestimation of
      actual canal size. Cervical preflaring increases the accuracy of apical size
      determination. CLINICAL SIGNIFICANCE: Thus, cervical preflaring is recommended
      before selection of IAF as it increases the accuracy of apical size
      determination.

PMID- 23151710
TI  - The study of role of stress in children with behavior disorders and orofacial
      lesions.
AB  - AIM: (1) To study the behavior disorders in children between 5 to 15 years. (2)
      To study the role of stress in causing behavior disorders. (3) To interpret the
      orofacial findings in children with behavior disorders. (4) Correlate the
      orofacial findings with behavior disorder. MATERIALS AND METHODS: Ninty children
      with behavior problems between age of 5 to 15 years along with their parents who
      visited the Department of Child-Guidance Clinic, BYL Nair Charitable Hospital,
      Mumbai. Intraoral examinations were conducted. Behavioral disorders and factors
      predisposing to those disorders were recorded. RESULTS: Behavior disorders with
      orofacial lesions was more common in age group of 8 to 10 years. The children
      were continuously under stress, which manifested in the form of various orofacial
      disorders or oral lesions. Most common orofacial condition was bruxism.
      CONCLUSION: Awareness of behavior disorders in dental treatment should guide the
      pediatric dentist to seek child psychiatric consultation for behavioral disorders
      to enable early evaluation of the underlying disorder. CLINICAL SIGNIFICANCE: The
      present study suggested that orofacial and behavior characteristics can serve as
      markers to diagnose children with behavioral disorders. It also serves as a guide
      to dental clinicians to refer such children to psychiatrists or pediatricians for
      early identification, prevention and treatment.

PMID- 23151711
TI  - Epidemiological survey on edentulousness.
AB  - India has a large geriatric population of 77 millions, comprising 7.7% of its
      total population. One of the major handicaps in the elderly is loss of teeth,
      affecting their mastication, dietary intake and nutritional status. AIMS AND
      OBJECTIVES: The present study was planned to assess the level of edentulousness,
      cause of edentulousness, denture wearing and denture needs of the middle and
      elderly in the society and study was correlated between habits and socioeconomic
      variables, diet and body mass index (BMI). MATERIALS AND METHODS: A total of 500
      subjects (random sampling) from dental outpatient were studied. A prepared
      questionnaire was developed, explained, interviewed and questions were filled
      personally. RESULTS: The level of edentulousness was found to be high in the
      subjects with low socioeconomic status and in advancing age with no significant
      difference between male and females. Another finding was very low level of
      denture wearing of 62% needing complete denture and partial denture only 10.4% of
      subjects wearing dentures. Mixed diet population had higher level of
      edentulousness compared with vegetarians. The BMI was correlated with level of
      edentulousness. CONCLUSION: The study clearly showed that there is lack of dental
      awareness, so dental education and motivation in very important. The study
      concludes that the need for prosthodontics care will increase due to the increase
      in life span. This study is clinically significant with regard to knowing the
      root cause of edentulism, either partial or complete. Out of 62% tooth loss,
      dental caries (37.4%) topped the cause for tooth loss followed by combination of
      dental caries and periodontal disease (12.2%).

PMID- 23151712
TI  - Enhancing white and pink esthetics using porcelain laminates in a fluorosis
      patient.
AB  - Fluorosis can cause enamel degeneration to varying extent depending on the
      fluoride levels prevalent in that particular area. It can range from slight
      mottling of enamel to severe degeneration leading to demineralization and
      resultant discoloration. In the latter case, treatment options are limited to
      bonding of the outer surface of teeth either with composite or porcelain.
      CLINICAL SIGNIFICANCE: Porcelain laminates offer an excellent solution to enhance
      esthetics in a patient with fluorosis as it combines the advantage of being
      highly esthetic along with being conservative in its penetration to enamel.

PMID- 23151713
TI  - Therapeutic extraction of lower incisor for orthodontic treatment.
AB  - Lower incisor extraction in orthodontic treatment was very rare modality of
      orthodontic treatment because there are few patients who meet the standards for
      such treatment. Proper diagnosis and treatment planning should be done to achieve
      good occlusion and facial esthetics. Criteria for lower incisor extraction
      included degree of crowding, tooth size discrepancy, pathologic condition,
      vertical overbite, sagittal incisal relationship, skeletal growth pattern and age
      of the patient. This article comprises of a case of class I malocclusion treated
      with lower incisor extraction, with comprehensive analysis, diagnosis and
      treatment planning, treatment results were satisfactory. CLINICAL SIGNIFICANCE:
      Mandibular incisor extraction can be an effective treatment option in borderline
      cases with mild crowding in lower arch. Minimal alteration of mandibular arch
      form is key factor for success and stable results.

PMID- 23151714
TI  - Hands off and save teeth!

PMID- 23151715
TI  - Breath isoprene concentrations in persons undergoing general anesthesia and in
      healthy volunteers.
AB  - Human breath contains an abundance of volatile organic compounds (VOCs). Analysis
      of breath VOC may be used for diagnosis of various diseases or for on-line
      monitoring in anesthesia and intensive care. However, VOC concentrations largely
      depend on the breath sampling method and have a large inter-individual
      variability. For the development of breath tests, the influence of breath
      sampling methods and study subject characteristics on VOC concentrations has to
      be known. Therefore, we investigated the VOC isoprene in 62 study subjects during
      anesthesia and 16 spontaneously breathing healthy volunteers to determine (a) the
      influence of artificial and spontaneous ventilation and (b) the influence of
      study subject characteristics on breath isoprene concentrations. We used ion
      molecule reaction mass spectrometry for high-resolution breath-by-breath analysis
      of isoprene. We found that persons during anesthesia had significantly increased
      inspiratory and end-expiratory isoprene breath concentrations. Measured isoprene
      concentrations (median [first quartile-third quartile]) were in the anesthesia
      group: 54 [40-79] ppb (inspiratory) and 224 [171-309] ppb (end-expiratory),
      volunteer group: 14 [11-17] ppb (inspiratory) and 174 [124-202] ppb (end
      expiratory). Higher end-tidal CO(2) concentrations in ventilated subjects were
      associated with higher expiratory isoprene levels. Furthermore, inspiratory and
      end-expiratory isoprene concentrations were correlated during anesthesia (r =
      0.603, p < 0.001). Multivariate analysis showed that men had significantly higher
      end-expiratory isoprene concentrations than women. Rebreathing of isoprene from
      the anesthesia machine possibly accounts for the observed increase in isoprene in
      the anesthesia group.

PMID- 23151718
TI  - Neuronal circuits: Distinctly motivated circuits.

PMID- 23151719
TI  - Learning and memory: Dopamine boosts ageing memories.

PMID- 23151722
TI  - Prenatal p,p'-DDE exposure and neurodevelopment among children 3.5-5 years of
      age.
AB  - BACKGROUND: The results of previous studies suggest that prenatal exposure to
      bis[p-chlorophenyl]-1,1,1-trichloroethane (DDT) and to its main metabolite, 2,2
      bis(p-chlorophenyl)-1,1-dichloroethylene (DDE), impairs psychomotor development
      during the first year of life. However, information about the persistence of this
      association at later ages is limited. OBJECTIVES: We assessed the association of
      prenatal DDE exposure with child neurodevelopment at 42-60 months of age.
      METHODS: Since 2001 we have been monitoring the neurodevelopment in children who
      were recruited at birth into a perinatal cohort exposed to DDT, in the state of
      Morelos, Mexico. We report McCarthy Scales of Children's Abilities for 203
      children at 42, 48, 54, and 60 months of age. Maternal DDE serum levels were
      available for at least one trimester of pregnancy. The Home Observation for
      Measurement of the Environment scale and other covariables of interest were also
      available. RESULTS: After adjustment, a doubling of DDE during the third
      trimester of pregnancy was associated with statistically significant reductions
      of -1.37, -0.88, -0.84, and -0.80 points in the general cognitive index,
      quantitative, verbal, and memory components respectively. The association between
      prenatal DDE and the quantitative component was weaker at 42 months than at older
      ages. No significant statistical interactions with sex or breastfeeding were
      observed. CONCLUSIONS: These findings support the hypothesis that prenatal DDE
      impairs early child neurodevelopment; the potential for adverse effects on
      development should be considered when using DDT for malaria control.

PMID- 23151723
TI  - Interactions of everolimus and sorafenib in whole blood lymphocyte proliferation.
AB  - PURPOSE: Everolimus is an immunosuppressant that blocks growth factor-mediated
      proliferation of hematopoietic cells by targeting the mammalian target of
      rapamycin (mTOR). Sorafenib is a multikinase inhibitor that inhibits cell
      proliferation by arresting cells in the G0-G1 phase of the cell cycle. These
      agents are under investigation as combination therapy for various cancers.
      Because the two drugs individually inhibit lymphocyte proliferation, this study
      examined the effects of everolimus and sorafenib on lymphocyte proliferation in
      order to anticipate possible immunosuppression. METHODS: Inhibition of lymphocyte
      proliferation was evaluated ex vivo over a range of concentrations of these
      drugs, alone and in combination. Data analysis, using a population approach to
      characterize interactions, employed the Ariens noncompetitive interaction model,
      which was modified to accommodate interactions of the two drugs. RESULTS:
      Everolimus alone caused partial inhibition of lymphocyte proliferation, with a
      mean IC(50) of 4.5 nM for females and 10.5 nM in males. Sorafenib alone caused
      complete inhibition, with a mean IC(50) of 11.4 MUM and no difference between
      genders. CONCLUSION: The population estimate for the interaction term was greater
      than 1, suggesting that the two drugs exert slight antagonism in terms of
      inhibition of lymphocyte proliferation.

PMID- 23151725
TI  - Transplantation of bone marrow-derived endothelial progenitor cells attenuates
      cerebral ischemia and reperfusion injury by inhibiting neuronal apoptosis,
      oxidative stress and nuclear factor-kappaB expression.
AB  - The aim of the present study was to investigate the neuroprotective effects of
      bone marrow-derived endothelial progenitor cell (EPC) transplantation against
      cerebral ischemia/reperfusion (I/R) injury in rats and to delineate the possible
      underlying mechanisms. Cerebral I/R injury was established by 2 h of middle
      cerebral artery occlusion (MCAO) followed by reperfusion for 24 h. EPCs were
      isolated from bone marrow of the donor rats, grown in conditioned medium, and
      characterized by flow cytometry analysis of several surface markers. Labeled EPCs
      (106 cells) were infused into rats at the onset of reperfusion and 12 h after
      reperfusion via the tail vein. Infarct volume was assessed at 24 h after
      reperfusion by using triphenyltetrazolium chloride (TTC) staining. The expression
      of cell apoptosis-related proteins including Bcl-2 and Bax was determined by
      western blot analysis, and the activity of caspase-3 was also measured. We
      evaluated the activities of some antioxidative enzymes, such as superoxide
      dismutase (SOD), glutathione peroxidase (GSH-PX), the non-enzymatic scavenger
      glutathione (GSH) and detected the content of malondialdehyde (MDA) in the
      ischemic penumbra. Moreover, the expression of nuclear factor-kappaB (NF-kappaB)
      in the ischemic regions of rats was examined by immunohistochemical staining and
      western blot analysis. The results showed that transplantation of EPCs
      significantly reduced the cerebral infarct volume, decreased caspase-3 activity,
      upregulated Bcl-2 expression, and downregulated the expression of Bax and NF
      kappaB. Furthermore, reduced levels of MDA, significantly elevated activities of
      SOD and GSH as well as GSH-PX were also found in I/R rats transplanted with EPCs.
      Collectively, our data demonstrated that transplantation of bone marrow-derived
      EPCs exerts potent neuroprotective functions against cerebral I/R injury in rats,
      and the protective effects may be associated with its antioxidative and anti
      apoptotic properties.

PMID- 23151726
TI  - Infantile osteopetrosis with superimposed rickets.
AB  - BACKGROUND: Rickets is a complication of infantile osteopetrosis and pre
      treatment recognition of this complication is important. OBJECTIVE: To describe
      four children with infantile osteopetrosis complicated by rickets
      (osteopetrorickets) and review the relevant literature. MATERIALS AND METHODS:
      Retrospective chart analysis of four infants with osteopetrorickets and a
      systematic review of the relevant literature. RESULTS: We saw five children with
      infantile osteopetrosis, of whom four had superimposed rickets, for a period of
      12 years. The review of the literature (including the current four children),
      yielded 20 children with infantile osteopetrorickets. The children ranged in age
      from 2 months to 12 months. In all children, hepatosplenomegaly was found.
      Sixteen (80%) children had visual impairments and eight (40%) children had
      hearing impairments. Serum calcium-phosphorus product was less than 30 in 18
      children (90%). Twelve children (60%) were hypocalcemic and 18 (90%) were
      hypophosphatemic. In all children, the radiological examination demonstrated
      diffuse bony sclerosis and metaphyseal splaying and fraying of long bones. Five
      children (25%) had pathological fracture of extremities and 15 (75%) had rachitic
      rosary. CONCLUSION: Rickets as a complication to infantile osteopetrosis is not
      uncommon. Skeletal roentgenograms are of critical importance in the diagnosis of
      both osteopetrosis and superimposed rickets.

PMID- 23151728
TI  - Neuroimaging of nevoid basal cell carcinoma syndrome (NBCCS) in children.
AB  - Nevoid basal cell carcinoma syndrome (NBCCS, Gorlin syndrome) is an autosomal
      dominant condition with a wide range of manifestations, including multiple basal
      cell carcinomas, medulloblastoma, odontogenic keratocysts (OKC) and skeletal
      abnormalities. Children with NBCCS also have a predisposition for secondary
      cancers after exposure to ionising radiation. In children undergoing imaging for
      posterior fossa mass and/or maxillofacial cysts, certain additional findings can
      raise the possibility of NBCCS. Making the diagnosis can significantly impact
      patient management, especially for children with medulloblastoma.

PMID- 23151727
TI  - Nuclear medicine and multimodality imaging of pediatric neuroblastoma.
AB  - Neuroblastoma is an embryonic tumor of the peripheral sympathetic nervous system
      and is metastatic or high risk for relapse in nearly 50% of cases. Therefore,
      exact staging with radiological and nuclear medicine imaging methods is crucial
      for defining the adequate therapeutic choice. Tumor cells express the
      norepinephrine transporter, which makes metaiodobenzylguanidine (MIBG), an
      analogue of norepinephrine, an ideal tumor specific agent for imaging. MIBG
      imaging has several disadvantages, such as limited spatial resolution, limited
      sensitivity in small lesions and the need for two or even more acquisition
      sessions. Most of these limitations can be overcome with positron emission
      tomography (PET) using [F-18]2-fluoro-2-deoxyglucose [FDG]. Furthermore, new
      tracers, such as fluorodopa or somatostatin receptor agonists, have been tested
      for imaging neuroblastoma recently. However, MIBG scintigraphy and PET alone are
      not sufficient for operative or biopsy planning. In this regard, a combination
      with morphological imaging is indispensable. This article will discuss strategies
      for primary and follow-up diagnosis in neuroblastoma using different nuclear
      medicine and radiological imaging methods as well as multimodality imaging.

PMID- 23151729
TI  - Early interim FDG PET/CT prediction of treatment response and prognosis in
      pediatric Hodgkin disease-added value of low-dose CT.
AB  - BACKGROUND: Interim 18F-FDG PET helps predict outcome and tailor treatment in
      adults with Hodgkin disease (HD). OBJECTIVE: The purpose of this study was to
      assess predictive values of interim 18F-FDG PET/CT in children with HD and to
      define the potential added value to interim PET of low-dose CT. MATERIALS AND
      METHODS: Children were prospectively enrolled August 2002-April 2007. PET/low
      dose CT was performed at staging, after 2 cycles, at the end of treatment and
      during follow-up (mean 45 months). Treatment was unchanged regardless of interim
      results. PET and low-dose CT were read independently. RESULTS: Of 34 enrolled
      children (ages 3-17 years), 27 achieved complete response, 4 had progressive
      disease and 3 had relapse. Interim PET alone had positive and negative predictive
      values of 67% and 89%, respectively. Interim low-dose CT alone had positive and
      negative predictive values of 35% and 100%, respectively. Interim PET/CT had
      positive and negative predictive values of 75% and 96%, respectively.
      CONCLUSIONS: Early interim PET/CT was a good predictor of outcome. Integrated PET
      and low-dose CT improved the predictive value in children with HD.

PMID- 23151731
TI  - Humanizing work and work environment: a challenge for developing countries.

PMID- 23151730
TI  - Establishment of transgenic fibroblasts for producing recombinant human
      interferon-alpha and erythropoietin in bovine milk.
AB  - Human interferon alpha (IFN-alpha) and erythropoietin (EPO) have been used for a
      variety of purposes in clinical medicine. Human IFN-alpha has been used to treat
      several types of viral infection and cancer, as well as renal anemia, via
      stimulation of erythrocyte formation in the bone marrow. Transgenic cattle are
      excellent candidates for pharmaceutical production for humans due to their
      ability to produce recombinant proteins in milk. The purpose of the present study
      was to generate bovine transgenic fibroblasts capable of producing recombinant
      human IFN-alpha and EPO proteins in transgenic cattle milk. First, we analyzed
      the promoter activities of various bovine milk protein genes in HC11 mouse
      mammary epithelial cells. The bovine milk protein gene promoters were cloned into
      the Luc gene in a promoter-less pGL3-Basic vector. Presence of the alphaS1-casein
      promoter (-175 to +796 nt) resulted in an up to 16-fold increase in luciferase
      activity compared with that of the promoter-less construct. In addition, the
      human IFN-alpha and EPO genes were identified as significantly overexpressed in
      HC11 cells compared with the promoter-less construct. Together, the present
      results demonstrate that the construct with the alphaS1-casein promoter may
      induce secretion of recombinant human IFN-alpha and EPO into bovine milk.
      Furthermore, we generated transgenic fibroblasts expressing human IFN-alpha and
      EPO cDNA controlled by the alphaS1-casein promoter and two screening markers,
      enhanced green fluorescent protein and neomycin resistance. These transgenic
      fibroblasts may be a source of somatic cells for generating transgenic cattle
      that produce recombinant human IFN-alpha and EPO proteins during lactation.

PMID- 23151732
TI  - Design development scopes towards occupational wellness of women workers:
      specific reference to local agro based food processing industries in NE India.
AB  - Women workers constitute one of the most vulnerable segments of the country's
      labour force. They often face different workplace health challenges than men do.
      They are engaged in a range of work that extends from heavy, monotonous,
      repetitive jobs, which are in many times experienced with low-paid and involves
      in long hours of work. Women's workplace health problems are frequently
      compounded by getting more of the same at home--the "double jeopardy" of domestic
      work. Specific issues to improve the workers motivation leading to enhancement of
      productivity and improving occupational health and safety were addressed. Context
      specific application of ergonomics principles were studied in the process of
      designing of work related equipment of local fruit processing units, as well as
      in tea industry, covering 180 subjects selected purposively. Ergonomic risk
      factors prevailed among the workers associates productivity and relevant health
      issues were quantified using QEC, RULA. NMQ was used to gather data on prevalence
      of CTDs among the workers. Pineapple peeling, tea leaves plucking were found
      highly labour intensive, done manually. Postures scores found were very high.
      WRMSDs were prevalent among the workers. Scope for ergonomic design intervention
      was observed to improve productivity and occupational health.

PMID- 23151733
TI  - An integrative approach for evaluating work related musculoskeletal disorders.
AB  - OBJECTIVES: To develop a framework for evaluating the work related
      musculoskeletal disorders (WRMSDs). PARTICIPANTS: The proposed framework was
      tested on 15~jewellery manufacturing workers working at Chinchpokhli region in
      Mumbai, India and on 15 students studying in a management institute of Mumbai,
      India. METHODS: The framework has been broken into three phases. Phase 1-
      Ergonomic-risk evaluation; Phase 2--Musculoskeletal Disorders (MSD) evaluation
      and Phase 3--Clinical examination. Ergonomic-risk evaluation determines the
      relationship between work relatedness and musculoskeletal disorders.
      Musculoskeletal Disorders (MSD) evaluation tries to assess the presence of
      discomforts/disabilities in different body regions, through subjective evaluation
      tools. Ergonomic-risk evaluation involved QEC, PLIBEL and posture analysis by
      RULA. Musculoskeletal Disorders (MSD) evaluation involved administration of self
      reported questionnaires. Clinical examination involved muscle grading by a
      physiotherapist and back strength measurement. RESULTS: The framework suggested
      that ergonomic risk evaluation techniques, self reported body part questionnaires
      and physical measurement of physiological/biomechanical transients may have a
      relationship and can be used for the evaluation of work related musculoskeletal
      disorders. CONCLUSION: The proposed integrative approach will help in developing
      stage wise intervention strategies for work related musculoskeletal disorders.

PMID- 23151734
TI  - Prevalence of musculoskeletal disorders, levels of physical activity and
      perceived quality of life amongst construction site managers in Mumbai: a case
      study.
AB  - OBJECTIVE: The study aimed to explicate the levels of physical activity, the
      prevalence of musculoskeletal disorders (MSDs) and the perceived quality of life
      in construction site managers. PARTICIPANTS: Twenty two site managers working at
      a site in National Institute of Industrial Engineering (NITIE), Mumbai were
      selected for the study. METHODS: The participants responded to Nordic
      Musculoskeletal Questionnaire (NMQ) and the World Health Organization's (WHO),
      Quality of Life (QOL), and General Physical Activity (GPAQ) Questionnaires.
      RESULTS: In Quality of Life (QOL), 55% of the participants fell under 'good'
      psychological domain, while 55% categorized their work environment as 'poor'.
      Among musculoskeletal problems, low back pain and upper back pain was
      predominantly reported by the managers. Total physical activity was observed to
      be 836 Metabolic Equivalent of Task-minutes/week (MET-minutes/week). CONCLUSION:
      Although the Construction managers were not involved in any kind of rigorous work
      at the workplace, they were observed to be suffering from musculoskeletal
      problems of the back. 'Poor' category of environmental domain suggested that the
      working conditions needed to be improved and could be a reason for their ailment.

PMID- 23151735
TI  - Participatory ergonomics in redesigning a dyeing tub for fabric dyers.
AB  - OBJECTIVE: The 'saree' worn by women in India and many South Asian countries is
      dyed using a tub, usually in small scale units employing low capital and a small
      number of workers. While using these tubs, workers adopt awkward postures over
      long periods of time which results in severe discomfort in the neck, shoulders
      and lower extremities. The purpose of the study was to redesign the dyeing tub
      using a participatory approach and to study the impact of the newly designed tub
      on the reported body discomfort and rate of production. METHODS: Redesigning of
      the dyeing tub was carried out using three parallel participative processes--(1)
      eliciting the views of workers who use the tub, (2) interacting with the
      proprietors of the small scale dyeing units (the employers) and the tub
      manufacturers, and (3) iterative prototype tub development based on inputs from
      the first two processes. These processes facilitated involvement of the stake
      holders and the acceptance of change. The final prototype was tested by nine
      workers for a period of three months to evaluate the reduction in body discomfort
      and increase in rate of production (output). RESULTS: Studies on the impact of
      the new tub showed a reduction in discomfort level from 'severe' to 'moderate',
      and a mean increase of 7.9% in the output, confirming the benefits of the
      participative approach to ergonomics intervention. The involvement, trust and
      credibility generated by the participative process facilitated the acceptance of
      the final design.

PMID- 23151736
TI  - Demographic, cultural, clinical and rehabilitation associated variables
      predicting return to employment after the onset of a disability. From the editor.

PMID- 23151739
TI  - Characterisation of element profile changes induced by long-term dietary
      supplementation of zinc in the brain and cerebellum of 3xTg-AD mice by alternated
      cool and normal plasma ICP-MS.
AB  - Metal dyshomeostasis plays a crucial role in promoting several neurodegenerative
      diseases including Alzheimer's disease (AD), a condition that has been linked to
      deregulation of brain levels of Al, Fe, Mn, Cu, and Zn. Thus, quantitative multi
      element profiling of brain tissues from AD models can be of great value in
      assessing the pathogenic role of metals as well as the value of therapeutic
      interventions aimed at restoring metal homeostasis in the brain. In this study,
      we employed low resolution inductively coupled plasma mass spectrometry (ICP-MS)
      to evaluate levels of ultra-trace, trace, and major elements in brains and
      cerebella of 3xTg-AD mice, a well characterized transgenic (Tg) AD model. This
      method is based on alternated cool and hot plasma ICP-MS. The essay fulfilled
      analytical requirements for the quantification of 14 elements in the Central
      Nervous System (CNS) of our Tg model. Quantification of Li, Al, Cr, and Co, a
      procedure that requires a pre-concentration step, was validated by high
      resolution ICP-MS. Changes in element profiles occurring in 3xTg-AD mice were
      compared to the ones observed in wild type (WT) mice. We also investigated
      variations in element profiles in 3xTg-AD mice receiving a long-term (17 months)
      dietary supplementation of Zn. Our data indicate that, compared to WT animals,
      3xTg-AD mice displayed signs of altered brain metal homeostasis. We also found
      that long-term Zn administration promoted decreased brain levels of some metals
      (K, Ca, and Fe) and restored levels of Al, Cr, and Co to values found in WT mice.

PMID- 23151740
TI  - Choroid plexus coagulation for hydrocephalus not due to CSF overproduction: a
      review.
AB  - OBJECTIVE: This study aims to review the role of choroid plexus coagulation (CPC)
      for hydrocephalus not due to CSF overproduction. METHODS: The literatures
      covering CPC/cauterization/extirpation and ablation searched through PubMed were
      reviewed. RESULTS: The history of CPC goes back to early 1900s by open surgery.
      It has evolved to mainly an endoscopic surgery since 1930s. With the development
      of other treatment methods and the understanding of CSF dynamics, the application
      of CPC dramatically decreased by 1970s. In late 2000, there was a resurgence of
      CPC in combination with endoscopic third ventriculostomy (ETV) performed in
      Africa. CONCLUSIONS: CPC remains one of the options for the treatment of
      hydrocephalus in selected cases. CPC might provide a temporary reduction in CSF
      production to allow the further development of CSF absorption in infant. Adding
      CPC to ETV for infants with communicating hydrocephalus may increase the shunt
      independent rate thus avoiding the consequence of late complication related to
      the shunt device. This is important for patients who are difficult to be followed
      up, due to geographical and/or socioeconomic constrains. Adding CPC to ETV for
      obstructive hydrocephalus in infant may also increase the successful rate.
      Furthermore, CPC may be an option for cases with high chance of shunt
      complication such as hydranencephaly. In addition, CPC may act as an adjunct
      therapeutic measure for complex cases such as multiloculated hydrocephalus. In
      comparison with the traditional treatment of CSF shunting, the role of CPC needs
      to be further evaluated in particular concerning the neurocognitive development.

PMID- 23151741
TI  - Pseudoprogression after proton beam irradiation for a choroid plexus carcinoma in
      pediatric patient: MRI and PET imaging patterns.
AB  - PURPOSE: Pseudoprogression is a rare complication of radiation therapy, and
      discrimination between true progression and pseudoprogression is of paramount
      importance for further medical care. We present a case of intra-axial
      pseudoprogression following complementary proton radiation therapy for a choroid
      plexus carcinoma in a child. We aim to highlight radiological patterns of
      pseudoprogression after proton beam therapy. CASE REPORT: A 6-year-old girl
      presented with choroid plexus carcinoma, manifesting as change in behavior,
      tremor, and balance disorder. Partial resection and chemotherapy were performed.
      Complementary localized proton beam therapy (54 Gy) was administered on the
      residual tumor. Eight month follow-up MRI showed an abnormal, irregular, rim-like
      enhancement in the pons and both temporal lobes within the field of irradiation.
      These lesions had a low cerebral blood volume (CBV) on perfusion MR imaging and
      no restricted diffusion. However, the lesions were hypermetabolic on O-(2
      [18F]fluoroethyl)-L-tyrosine (FET)-PET MRI. Follow-up MRI showed disappearance of
      these lesions confirming the perfusion MR diagnosis of pseudoprogression.
      CONCLUSION: Based on this case, radiological patterns of pseudoprogression after
      proton beam therapy may be a low CBV and no restricted diffusion. Lesions can be
      hypermetabolic on FET-PET imaging.

PMID- 23151742
TI  - Fluorescent labeling of specific cysteine residues using CyMPL.
AB  - The unique reactivity and relative rarity of cysteine among amino acids makes it
      a convenient target for the site-specific chemical modification of proteins.
      Commercially available fluorophores and modifiers react with cysteine through a
      variety of electrophilic functional groups. However, it can be difficult to
      achieve specific labeling of a particular cysteine residue in a protein
      containing multiple cysteines, in a mixture of proteins, or in a protein's native
      environment. This unit describes a procedure termed CyMPL (Cysteine Metal
      Protection and Labeling), which enables specific labeling by incorporating a
      cysteine of interest into a minimal binding site for group 12 metal ions (e.g.,
      Cd2+ and Zn2+). These sites can be inserted into any region of known secondary
      structure in virtually any protein and cause minimal structural perturbation.
      Bound metal ions protect the cysteine from reaction while background cysteines
      are covalently blocked with non-fluorescent modifiers. The metal ions are
      subsequently removed and the deprotected cysteine is labeled specifically.

PMID- 23151743
TI  - Sample preparation, data collection, and preliminary data analysis in
      biomolecular solution X-ray scattering.
AB  - In addition to the classic methods of structural biology--X-ray crystallography
      and NMR--solution X-ray scattering (SAXS) is playing an increasingly important
      role in structural investigation of biological macromolecules. However, the
      simultaneous ease of SAXS data collection and sophistication of its data analysis
      tools can present challenges to the investigator. Any sample, whether pure or
      contaminated, whether monodisperse or polydisperse, will yield scattering data,
      and it is up to the user to ensure the absence of artifacts and to choose a
      proper structural modeling strategy. This unit discusses experimental aspects of
      X-ray solution scattering, including sample preparation and data collection, as
      well as the steps in data processing and preliminary analysis required to ensure
      the absence of artifacts. The goal is to summarize everything than can go wrong
      with SAXS data measurement so the user can have confidence in the data before
      undertaking structural modeling.

PMID- 23151744
TI  - Protein databases on the internet.
AB  - Protein databases have become a crucial part of modern biology. Huge amounts of
      data for protein structures, functions, and particularly sequences are being
      generated. Searching databases is often the first step in the study of a new
      protein. Comparison between proteins or between protein families provides
      information about the relationship between proteins within a genome or across
      different species, and hence offers much more information than can be obtained by
      studying only an isolated protein. In addition, secondary databases derived from
      experimental databases are also widely available. These databases reorganize and
      annotate the data or provide predictions. The use of multiple databases often
      helps researchers understand the structure and function of a protein. Although
      some protein databases are widely known, they are far from being fully utilized
      in the protein science community. This unit provides a starting point for readers
      to explore the potential of protein databases on the Internet.

PMID- 23151745
TI  - Proteolytic fingerprinting of complex biological samples using combinatorial
      libraries of fluorogenic probes.
AB  - Proteases have garnered interest as candidate biomarkers and therapeutic targets
      for many human diseases. A key challenge is the identification and
      characterization of disease-relevant proteases in the complex milieu of
      biological fluids such as serum, plasma, and bronchoalveolar lavage, in which a
      multitude of hydrolases act in concert. This unit describes a protocol to map the
      global proteolytic substrate specificities of complex biological samples using a
      concise combinatorial library of internally quenched fluorogenic peptide probes
      (IQFPs). This substrate profiling approach provides a global and quantitative
      comparison of protease specificities between different biological samples. Such a
      comparative analysis can lead to the identification of disease-specific
      'fingerprints' of proteolytic activities with potential utility in diagnosis and
      therapy.

PMID- 23151746
TI  - Circular dichroism in protein folding studies.
AB  - Protein folding is a biological process of both fundamental significance and
      practical importance, and protein misfolding is implicated in a number of serious
      diseases of both humans and animals. The study of protein folding requires a
      technique that is able to monitor changes in protein structure in solution, with
      millisecond time resolution. Ultraviolet circular dichroism (CD) is such a
      technique, providing information on both secondary and tertiary protein
      structure. This unit describes the procedures for performing CD experiments for
      the study of protein folding, and identifies commonly encountered problems and
      their solutions.

PMID- 23151747
TI  - Preparation and extraction of insoluble (inclusion-body) proteins from
      Escherichia coli.
AB  - High-level expression of many recombinant proteins in Escherichia coli leads to
      the formation of highly aggregated protein commonly referred to as inclusion
      bodies. Inclusion bodies are normally formed in the cytoplasm; however, if a
      secretion vector is used, they can form in the periplasmic space. Inclusion
      bodies can be recovered from cell lysates by low-speed centrifugation. Following
      pre-extaction (or washing), protein is extracted from washed pellets using
      guanidine?HCl. The solubilized and unfolded protein is either directly folded or
      further purified by gel filtration in the presence of guanidine?HCl as described
      in this unit. A support protocol describes the removal of guanidine?HCl from
      column fractions so they can be monitored by SDS-PAGE.

PMID- 23151749
TI  - Lack of association between STK39 and hypertension in the Chinese population.
AB  - Genome-wide association study (GWAS) has identified serine/threonine kinase 39
      (STK39) as a candidate gene for hypertension. A replication study provided
      supporting evidence that STK39 functional polymorphism rs35929607 was associated
      with hypertension. Recently, another study also showed rs6749447 within the STK39
      was associated with blood pressure responses. However, these studies were all
      conducted in Caucasians. Thus, we carried out a case-control study to test
      whether STK39 is a common candidate gene for hypertension, and to examine the
      interaction of genetic factors and non-genetic risk factors in the Chinese
      population. Thousand twenty four hypertensive cases and 1024 controls were
      genotyped for five polymorphisms. Four single-nucleotide polymorphisms (SNPs) are
      located within STK39, and rs4977950, the SNP that showed the strongest signal is
      located in a gene desert. Results indicated that none of these SNPs was
      associated with hypertension in the Chinese population. Logistic regression
      analysis found body mass index (BMI) and triglyceride level were higher in the
      hypertension group when compared with the control group. Multifactor
      dimensionality reduction analysis indicated that the interaction between BMI and
      rs4977950 may have an impact on hypertension. Taken together, the present study
      found no evidence that STK39 was associated with hypertension in the Chinese
      population. Instead, non-genetic risk factors such as BMI have an important role
      in Chinese hypertensive subjects, and the 'missing inheritability' requires
      further investigation.

PMID- 23151748
TI  - The association of c-reactive protein with arterial compliance in asymptomatic
      young adults: the Bogalusa heart study.
AB  - Atherogeneis is a chronic progressive syndrome caused by endothelial dysfunction,
      vascular inflammation, vessel wall remodeling and eventual vascular flow
      compromise. Emerging data suggest that arterial compliance inversely correlates
      with atherogenesis and cardiovascular (CV) events. However, information is scant
      on the association of chronic systemic inflammation with arterial elasticity in
      young asymptomatic adults. The association of hsC-reactive protein (CRP) and
      central-vascular compliance was studied in 641 individuals (45.2% males; 71.8%
      whites), aged 31-43 years enrolled in the Bogalusa Heart Study. The measured
      variables included large-artery compliance (capacitive, C1), representative of
      the aorta and its major branches; and small-artery compliance (oscillatory, C2),
      representative of the distal part of the circulation; hsCRP, as a measure of
      systemic inflammation; along with traditional CV risk factor variables.
      Significant race and sex differences were noted for C1 (white males>black males P
      value <0.0001; males>females P-value 0.04), C2 (whites>blacks P-value 0.0004;
      males>females P-value<0.0001) and hsCRP (blacks>whites P-value 0.03;
      females>males P-value 0.002). Mean values of C1 in subjects with high hsCRP
      levels (>3 mg l(-1)) were significantly lower than those with average (1-3 mg l(
      1)) and low levels (<1 mg l(-1)) (14.2 ml per mmHg * 10 versus 15.2 ml per mm Hg
      * 10 versus 15.7 ml per mmHg * 10, P for trend=0.02), after adjusting for age,
      race, sex and body surface area (BSA). hsCRP showed a trend toward inverse
      correlation with C1 (-0.07, P=0.07) but no such trend for C2, after adjusting for
      race and sex. In the multivariate linear regression model, adding age, race, sex,
      BSA, mean arterial pressure, insulin resistance, lipoprotein variables and
      smoking status, the effect persisted between C1 and hsCRP (beta=-0.35, P=0.01).
      In an asymptomatic population of young adults, hsCRP predicts reduced large
      artery compliance (C1). These findings support the role of systemic inflammation
      in early pathological changes in artery wall in atherogenesis. Small-artery
      compliance (C2) however did not correlate with hsCRP.

PMID- 23151750
TI  - Serum potassium predicts time to blood pressure response among African Americans
      with hypertensive nephrosclerosis.
AB  - It is not known whether serum potassium levels affect blood pressure response to
      antihypertensive medication. The African American Study of Kidney Disease and
      Hypertension (AASK) Genomics Study (N=828) is a subset of the AASK trial that
      randomized 1094 African American men and women with hypertensive nephrosclerosis
      to ramipril, amlodipine or metoprolol. Participants were also randomized to a
      usual (102-107 mm Hg) or low (<=92 mm Hg) mean arterial pressure (MAP) treatment
      goal. Time-to-event analyses were used to determine the relationship between
      serum potassium at randomization and time (days) to reach an MAP of 107 mm Hg.
      Mean baseline serum potassium was 4.22 mmol l(-1) (s.d.+/-0.56 and range 2.8-6.0)
      and the median days to reach target MAP was 32 (interquartile range 8-95). The
      adjusted hazard ratio (HR) for each 1 mmol l(-1) increase in serum potassium was
      1.31 (95% confidence interval (CI): 1.08-1.59) in the usual MAP group, and 1.21
      (95% CI: 1.02-1.44) in the low MAP group. Secondary findings suggested that women
      in the usual MAP group on amlodipine were more likely to reach target MAP
      compared with women randomized to ramipril (HR: 2.05, 95% CI: 1.30-3.21). Older
      subjects in the low MAP group (>=55 years) were also more likely to reach target
      MAP on amlodipine compared with ramipril (HR: 1.57, 95% CI: 1.03-2.38). Serum
      potassium appears to be a significant predictor of time to blood pressure
      response, independent of drug class. The effect of serum potassium on blood
      pressure response to antihypertensive medications needs to be further studied in
      different patient populations.

PMID- 23151751
TI  - Sodium and potassium intake patterns and trends in South Korea.
AB  - We examined major trends and patterns regarding sodium and potassium intake and
      the ratio of sodium and potassium in the diets of South Koreans. We used data
      from 24-h dietary recall data from 10,267, 8819 and 9264 subjects ages > or =2
      years in the 1998, 2005 and 2009 Korean National Health and Nutrition Examination
      Surveys, respectively. Mean sodium intake did not change significantly between
      1998 and 2009 (4.6 vs. 4.7 g per day), while potassium intake increased
      significantly (2.6 vs. 2.9 g per day (P<0.001)). The major dietary sodium sources
      were kimchi, salt, soy sauce and soybean paste, and most potassium came from
      unprocessed foods (white rice, vegetables, kimchi and fruits). About 50% of the
      participants consumed > or =4 g of sodium per capita per day. The proportion of
      respondents consuming four to six grams of potassium per capita per day increased
      from 10.3% in 1998 to 14.3% in 2009 (P<0.001), and the sodium-potassium ratio
      decreased from 1.88 to 1.71 (P<0.001). One major implication is that efforts to
      reduce sodium in processed foods will be ineffective and future efforts must
      focus on both education to reduce use of sodium in food preparation and sodium
      replacement in salt, possibly with potassium.

PMID- 23151752
TI  - Reply: To PMID 18371596.

PMID- 23151753
TI  - Compensation for spill-in and spill-out partial volume effects in cardiac PET
      imaging.
AB  - BACKGROUND: Partial volume effects (PVEs) in PET imaging result in incorrect
      regional activity estimates due to both spill-out and spill-in from activity in
      neighboring regions. It is important to compensate for both effects to achieve
      accurate quantification. In this study, an image-based partial volume
      compensation (PVC) method was developed and validated for cardiac PET. METHODS
      AND RESULTS: The method uses volume-of-interest (VOI) maps segmented from
      contrast-enhanced CTA images to compensate for both spill-in and spill-out in
      each VOI. The PVC method was validated with simulation studies and also applied
      to images of dog cardiac perfusion PET data. The PV effects resulting from
      cardiac motion and myocardial uptake defects were investigated and the efficacy
      of the proposed PVC method in compensating for these effects was evaluated.
      RESULTS: Results indicate that the magnitude and the direction of PVEs in cardiac
      imaging change over time. This affects the accuracy of activity distributions
      estimates obtained during dynamic studies. The defect regions have different PVEs
      as compared to the normal myocardium. Cardiac motion contributes around 10% to
      the PVEs. PVC effectively removed both spill-in and spill-out in cardiac imaging.
      CONCLUSIONS: PVC improved left ventricular wall uniformity and quantitative
      accuracy. The best strategy for PVC was to compensate for the PVEs in each
      cardiac phase independently and treat severe uptake defects as independent
      regions from the normal myocardium.

PMID- 23151754
TI  - Stress-only imaging: faster, cheaper, less radiation. So what's the hold up?

PMID- 23151755
TI  - Urinary bladder stones in women.
AB  - PURPOSE: The objective of this study was to review the history, epidemiology,
      diagnosis, and current management techniques for bladder stones (BS) in women.
      METHODS: A MEDLINE search for articles published from 1950 to 2011 was done using
      a list of terms related to BS including calculi, cystolithiasis, stones, urinary
      bladder, and women. RESULTS: Approximately 5% of all BS occur in women and are
      usually associated with foreign bodies (sutures, synthetic tapes, or meshes) or
      urinary stasis. Bladder stones can be asymptomatic but may result in hematuria,
      recurrent infections, and irritable symptoms. Stones can be detected by x-ray,
      ultrasound, or computed tomography scan and frequently at the time of routine
      cystourethroscopy performed during pelvic surgery. Because BS is a sign of an
      underlying problem, definite treatment of the underlying abnormality is nearly
      always indicated. The preferred treatment for BS is endoscopic transurethral
      fragmentation of the stone (cystolithotripsy). Any associated suture or synthetic
      mesh can be removed or cut flush with the bladder mucosa. Partial resection of
      the mesh with cystotomy should be considered whenever transurethral treatment
      failed. When stone burden is large, percutaneous endoscopic disintegration or
      open suprapubic cystolithotomy is preferable. Extracorporeal shockwave
      lithotripsy has been demonstrated to be simple, effective, and well tolerated.
      However, ancillary procedures are required in a significant number of patients.
      CONCLUSIONS: The increased usage of synthetic material in reconstructive pelvic
      floor surgery in women will probably increase the incidence of BS on intravesical
      foreign bodies. Bladder stones should be ruled out in women investigated for
      irritable bladder symptoms or recurrent urinary infection.

PMID- 23151756
TI  - Use of levonorgestrel-releasing intrauterine system in the prevention and
      treatment of endometrial hyperplasia.
AB  - Endometrial hyperplasia is a commonly seen gynecological condition that affects
      women of all age groups. Whereas hysterectomy is the most preferred treatment
      option for complex endometrial hyperplasia with atypia, there is no consensus
      regarding the first-line management of women with hyperplasia without cytological
      atypia. Oral progestogen therapy was used with some success. Nonetheless, it may
      be plausible to argue that women with endometrial hyperplasia need continuous
      treatment and high level of compliance to ensure complete regression, which may
      not be guaranteed with oral therapy. Observational studies suggested that
      levonorgestrel-releasing intrauterine system (LNG-IUS) has been successfully used
      to treat endometrial hyperplasia without cytological atypia and selected cases of
      atypical endometrial hyperplasia. Furthermore, there is strong evidence from
      randomized controlled trials that LNG-IUS prevents the development of endometrial
      hyperplasia in exogenous estrogen users; however, its protective role and safety
      in tamoxifen-treated breast cancer survivors remain uncertain. This article
      evaluates the current evidence for the use of LNG-IUS, releasing 20 MUg of LNG
      per day, in the prevention and treatment of endometrial hyperplasia.

PMID- 23151757
TI  - Uterine rupture during trial of labor: controversy of induction's methods.
AB  - The rate of attempted vaginal birth after cesarean has decreased during the past
      15 years. Most of the change since the mid 1990s is the result of increasing
      reports of uterine rupture during trial of labor, with the highest rates related
      to labor induction. Not all induction agents have the same magnitude of increased
      risk of uterine rupture, and there have been only a small number of randomized
      controlled trials of labor induction in women with previous cesarean delivery.
      Evaluation of the evidence on specific methods of induction reveals that the
      lowest rate of uterine rupture occurs with oxytocin at 1.1% (95% confidence
      interval [CI], 0.9%-1.5%) then dinoprostone at 2% (95% CI, 1.1%-3.5%), and the
      highest rate is with misoprostol, 6% (95% CI, 0.74%-51.4%). We review the
      incidence of uterine rupture during induction of labor after previous cesarean
      and examine the methods of induction and the safety of different techniques for
      cervical ripening, induction, and/or augmentation of labor in women with previous
      cesarean delivery.

PMID- 23151758
TI  - Enduring eponyms: the mystery of the Martorell ulcer.

PMID- 23151763
TI  - It's that time of year again: have you read the 2013 Office of Inspector General
      work plan?
AB  - The Work Plan is useful because it gives providers a preview of many of the OIG's
      enforcement priorities planned for fiscal year 2013.Wound care providers should
      take advantage of this opportunity to determine how to focus their compliance
      program activities over the next 12 months.Wound care providers should read the
      Work Plan for Fiscal Year 2013 for further information and references about the
      OIG issues. The Work Plan will help you to identify corporate compliance risk
      areas that you should audit and for which you should create/upgrade policies. Be
      sure to read the document and take a proactive approach by conducting internal
      audits to identify areas of improvement that you can make before you receive an
      external audit.

PMID- 23151764
TI  - Continuous topical oxygen for the treatment of chronic wounds: a pilot study.
AB  - Oxygen is essential for all stages of wound healing. Previous research has shown
      topical administration of oxygen to have positive effects on wound healing. In
      this study, the application of transdermal continuous topical oxygen therapy
      (TCOT) was evaluated for its effect on chronic wound healing in 9 patients. After
      4 weeks of treatment, mean wound surface area and wound infection checklist
      scores were significantly reduced. Signs of bacterial damage were also reduced.
      Findings from this study suggest TCOT may be beneficial in promoting chronic
      wound healing.

PMID- 23151765
TI  - Using color to guide debridement.
AB  - Chronic wounds are typically halted in the inflammatory stage of wound healing
      secondary to a prolonged inflammatory response of the body to bacterial
      colonization, as planktonic bacteria and biofilm and senescent cells present at
      the wound's edges. Surgical debridement of these wounds is a critical step taken
      by the treating physician to attain complete healing. In order for debridement to
      successfully reset the stages of wound healing, residual biofilm and senescent
      cells must be removed. Despite the importance of complete and thorough
      debridement, few methods exist, and even fewer articles have been written
      describing techniques to ensure that all portions of a wound are equally
      addressed with each procedure. Using methylene blue dye to color the wound allows
      the surgeon to address and debride all portions of the wound adequately. In
      addition, the surgeon must be very familiar with what the normal tissue colors
      are following removal of the methylene blue-dyed tissue. Getting to tissue with
      those colors provides an end point to the debridement and helps prevent removal
      of excess healthy tissue. This article describes the primary author's technique
      for staining tissues with methylene blue dye prior to wound debridement, as well
      as the colors to look for to signal completion of surgery. In addition, a review
      of biofilm and senescent cells is presented as both are targeted but frequently
      missed when wounds are incompletely debrided.

PMID- 23151766
TI  - Initial clinical assessment of a novel multifunctional topical ointment for
      difficult-to-heal wounds: a case series.
AB  - Chronic wounds are characterized by prolonged inflammation, bacterial bioburden,
      and ischemia. These factors represent the barriers to wound healing that need to
      be addressed in order to achieve wound closure. The authors performed the initial
      clinical testing of WinVivo Wound Ointment ("WinVivo"), a novel topical ointment
      containing several botanicals that have been previously shown to promote
      favorable wound environment and advance wound healing. In this series of 13
      patients with difficult-to-heal lower-extremity wounds, WinVivo was well
      tolerated and demonstrated the ability to simultaneously support granulation
      tissue formation; decrease the amount of exudate, edema, and malodor; and reduce
      pain. The ulcers included in this study have been present for a minimum of 3
      weeks and a maximum of 5 years prior to the start of treatment with WinVivo.
      Eight of 13 wounds have previously been treated with at least 1 type of advanced
      wound healing modality, such as dermal substitutes or negative-pressure wound
      therapy. Treatment with WinVivo lasted for 3 to 12 weeks and resulted in a mean
      88% wound closure, with 4 wounds healing completely. In addition to significant
      reduction in wound size, all patients have exhibited other clinical benefits,
      suggesting overall improvement in wound conditions. Future studies in a larger
      population, as well as case-control studies comparing WinVivo with a standard of
      care, are therefore warranted to further evaluate the efficacy of this new
      treatment.

PMID- 23151767
TI  - Martorell hypertensive ischemic leg ulcer: an underdiagnosed Entity(c).
AB  - Martorell hypertensive ischemic leg ulcer represents rapidly progressive and
      extremely painful ulcers that are frequently underdiagnosed. These occur most
      commonly on the lateral-dorsal calf and are associated with hypertension and
      diabetes. This article will synthesize a review of the literature for the
      accurate diagnosis and treatment of this painful debilitating condition.

PMID- 23151769
TI  - Meaningful use expectations worklist.

PMID- 23151771
TI  - Aneurysm embolization grade: a predictive tool for aneurysm recurrence after coil
      embolization.
AB  - BACKGROUND: Coil embolization has gained importance in the management of
      intracranial aneurysms over the past decade. However, the recurrence risk after
      embolization mandates closer follow-up than surgical clip ligation. Currently,
      there is no reliable system for predicting aneurysm sac thrombosis. An aneurysm
      embolization grade (AEG) reported previously by the senior author (EMD) has been
      proposed as a tool for predicting the durability of aneurysm occlusion based on
      hemodynamic characteristics. Here, we present our internal validity results.
      METHODS: AEG and Raymond-Roy Occlusion Classification (RROC) scores were
      prospectively assigned to all aneurysms coiled from June 2008 to June 2011. The
      prospectively assigned AEG and RROC scores from the cerebral angiograms were
      collected for data analysis and validity assessment of the AEG system. 110
      consecutive patients who had aneurysm coil embolization were included in this
      study. RESULTS: The post-coiling AEG significantly predicted follow-up
      angiographic filling characteristics. Pairwise comparisons revealed that the
      follow-up AEG for those initially scored 'A' (complete obliteration) was
      significantly better than the contrast-flow groups. Significant differences were
      also noted between contrast-stasis and contrast-flow groups. A pairwise
      comparison between RROC scores demonstrated that only the RROC Type 1 could be
      used to predict follow-up occlusion durability. Stent placement in wide-neck
      aneurysms had no effect on initial AEG, RROC, or long-term occlusion durability.
      Packing density significantly predicted initial AEG and RROC, but had no effect
      on long-term occlusion. CONCLUSIONS: The AEG system is uniquely based on
      angiographic filling characteristics of the aneurysm, and this study demonstrated
      its high predictive value for determining aneurysm sac thrombosis. Assigning an
      AEG to the aneurysm can guide the neurointerventionalist in discussions with the
      patient regarding the probability of aneurysm recurrence and potential need for
      retreatment.

PMID- 23151772
TI  - In vivo non-ionizing photoacoustic mapping of sentinel lymph nodes and bladders
      with ICG-enhanced carbon nanotubes.
AB  - We demonstrate the feasibility of mapping a sentinel lymph node (SLN) and urinary
      bladder by using modified single-walled carbon nanotubes (SWNTs) as a nonionizing
      photoacoustic (PA) contrast agent. To improve the PA sensitivity, indocyanine
      green (ICG) was conjugated with SWNTs and the optical absorption of SWNTs-ICG was
      enhanced by approximately four times compared to that of plain SWNTs at a
      concentration of 0.3 uM. In vivo PA imaging results showed that the SLN and
      bladder were clearly visualized due to accumulation of SWNTs-ICG. This implies
      that the SWNTs-ICG could be potentially utilized to identify SLNs in breast
      cancer patients and tracking vesicoureteral reflux in combination with PA
      imaging.

PMID- 23151773
TI  - Persistent environmental pollutants and couple fecundity: the LIFE study.
AB  - BACKGROUND: Evidence suggesting that persistent environmental pollutants may be
      reproductive toxicants underscores the need for prospective studies of couples
      for whom exposures are measured. OBJECTIVES: We examined the relationship between
      selected persistent pollutants and couple fecundity as measured by time to
      pregnancy. METHODS: A cohort of 501 couples who discontinued contraception to
      become pregnant was prospectively followed for 12 months of trying to conceive or
      until a human chorionic gonadotrophin (hCG) test confirmed pregnancy. Couples
      completed daily journals on lifestyle and provided biospecimens for the
      quantification of 9 organochlorine pesticides, 1 polybrominated biphenyl, 10
      polybrominated diphenyl ethers, 36 polychlorinated biphenyls (PCBs), and 7
      perfluorochemicals (PFCs) in serum. Using Cox models for discrete time, we
      estimated fecundability odds ratios (FORs) and 95% CIs separately for each
      partner's concentrations adjusting for age, body mass index, serum cotinine,
      serum lipids (except for PFCs), and study site (Michigan or Texas); sensitivity
      models were further adjusted for left truncation or time off of contraception (<=
      2 months) before enrollment. RESULTS: The adjusted reduction in fecundability
      associated with standard deviation increases in log-transformed serum
      concentrations ranged between 18% and 21% for PCB congeners 118, 167, 209, and
      perfluorooctane sulfonamide in females; and between 17% and 29% for p,p'-DDE and
      PCB congeners 138, 156, 157, 167, 170, 172, and 209 in males. The strongest
      associations were observed for PCB 167 (FOR 0.79; 95% CI: 0.64, 0.97) in females
      and PCB 138 (FOR = 0.71; 95% CI: 0.52, 0.98) in males. CONCLUSIONS: In this
      couple-based prospective cohort study with preconception enrollment and
      quantification of exposures in both female and male partners, we observed that a
      subset of persistent environmental chemicals were associated with reduced
      fecundity.

PMID- 23151774
TI  - Is it time to shift to better characterization of patients in trials assessing
      novel antidepressants? An example of two relapse prevention studies with
      agomelatine.
AB  - The present paper reports in parallel the findings of the two studies that
      evaluated the efficacy of agomelatine in preventing relapse of depression. It
      describes the methodological adjustments made between the first and the second
      trial, particularly in relation to patient selection and accuracy of diagnosis of
      depression. Patients with major depressive disorder who responded to an 8/10-week
      course of agomelatine 25-50 mg treatment were randomly assigned to receive
      continuation treatment with agomelatine or placebo during a 24-week, randomized,
      double-blind treatment period with an optional 18- or 20-week double-blind
      extension period. The cumulative probability of relapse was calculated using the
      Kaplan-Meier method of survival analysis. Study 1 lacked assay sensitivity
      because of an unexpectedly low relapse rate in the placebo arm, but was
      instructive in showing that the agomelatine effect was better than placebo only
      in those patients with higher symptom levels at baseline. Study 2 showed a robust
      benefit of agomelatine - a two-fold reduction in the relapse rate - observed at
      least up to 10 months in both the overall population and the more severely
      depressed patients. The methodological adjustments introduced in study 2 (e.g. a
      minimum subscore calculated from eight specific Hamilton Depression Rating Scale
      items, the use of the self-rating questionnaire Hospital Anxiety Depression Scale
      and the Sheehan questionnaire) have assured an adequate severity of depression
      not only on the basis of ratings of symptom severity but also on measures of
      functional impairment. We did not find increased severity of symptoms in study 2,
      but we hypothesize that the increased demands on investigators improved the
      quality of recruitment to represent more real-world patients. Adopting these
      innovations could contribute towards lower failure rates for future placebo
      controlled clinical trials in the field.

PMID- 23151775
TI  - Air-conducted oVEMPs provide the best separation between intact and superior
      canal dehiscent labyrinths.
AB  - OBJECTIVE: First, to define the best single-step suprathreshold screening test
      for superior canal dehiscence syndrome (SCDS); second, to obtain further insight
      into the relative sensitivity of vestibular afferents to sound vibration in the
      presence of a superior canal dehiscence. STUDY DESIGN: Prospective study.
      SETTING: Tertiary referral center. PATIENTS: Eleven patients with surgically
      confirmed SCDS (mean, 50 yr; range, 32-66 yr) and 11 age-matched, healthy
      subjects (right ear only) with no hearing or vestibular deficits (mean, 50 yr;
      range, 33-66 yr). INTERVENTION: All subjects completed ocular and cervical
      vestibular evoked myogenic potential (o- and cVEMP) testing in response to air
      conduction (click and 500 Hz tone burst) and midline bone conduction (reflex
      hammer and Mini-shaker) stimulation. MAIN OUTCOME MEASURES: OVEMP n10 amplitude
      and cVEMP corrected peak-to-peak amplitude. RESULTS: OVEMP n10 amplitudes were
      significantly higher in SCDS when compared with healthy controls in response to
      all stimuli with the exception of reflex hammer. Likewise, cVEMP-corrected peak
      to-peak amplitudes were significantly higher in SCDS when compared with healthy
      controls for air conduction stimulation (click and 500 Hz toneburst). However,
      there were no significant differences between groups for midline taps (reflex
      hammer or mini-shaker). Receiver operating characteristic curves demonstrated
      that oVEMPs in response to air conduction stimulation provided the best
      separation between SCDS and healthy controls. CONCLUSION: OVEMPs in response to
      air conduction stimulation (click and 500 Hz toneburst) provide the best
      separation between SCDS and healthy controls and are therefore the best single
      step screening test for SCDS.

PMID- 23151776
TI  - Developmental effects of family environment on outcomes in pediatric cochlear
      implant recipients.
AB  - OBJECTIVE: To examine and compare the family environment of preschool- and school
      age children with cochlear implants and assess its influence on children's
      executive function and spoken language skills. STUDY DESIGN: Retrospective
      between-subjects design. SETTING: Outpatient research laboratory. PATIENTS:
      Prelingually deaf children with cochlear implants and no additional disabilities
      and their families. INTERVENTION(S): Cochlear implantation and speech-language
      therapy. MAIN OUTCOME MEASURES: Parents completed the Family Environment Scale
      and the Behavior Rating Inventory of Executive Function (or the preschool
      version). Children were tested using the Peabody Picture Vocabulary Test-4 and
      either the Preschool Language Scales-4 or the Clinical Evaluation of Language
      Fundamentals-4. RESULTS: The family environments of children with cochlear
      implants differed from normative data obtained from hearing children, but average
      scores were within 1 standard deviation of norms on all subscales. Families of
      school-age children reported higher levels of control than those of preschool-age
      children. Preschool-age children had fewer problems with emotional control when
      families reported higher levels of support and lower levels of conflict. School
      age children had fewer problems with inhibition but more problems with shifting
      of attention when families reported lower levels of conflict. School-age
      children's receptive vocabularies were enhanced by families with lower levels of
      control and higher levels of organization. CONCLUSION: Family environment and its
      relation to language skills and executive function development differed across
      the age groups in this sample of children with cochlear implants. Because family
      dynamics is one developmental/environmental factor that can be altered with
      therapy and education, the present results have important clinical implications
      for family-based interventions for deaf children with cochlear implants.

PMID- 23151777
TI  - Mobile posturography:  posturographic analysis of daily-life mobility.
AB  - OBJECTIVE: Mobility is crucial to maintain a sufficient quality of life.
      Posturography should be therefore focused on the investigation of daily-life
      activities ("mobile posturography"). Nowadays, postural control is often
      estimated by stance tasks on a force plate under different sensorimotor
      conditions. This technique applies an indirect approximation of the center of
      body mass and is not related to tasks required for mobility. An alternative
      approach would be the direct measurement of body sway during daily-life
      conditions close to the center of body mass. The present study was aimed at
      investigating normal age-dependent postural control strategies by analyzing the
      body sway of male and female subjects in daily-life tasks. Furthermore, the
      results were compared with data of age- and sex-matched vestibular disorders to
      determine the sensitivity of the "mobile posturography". STUDY DESIGN:
      Prospective study. PATIENTS: The patient group included 76 subjects, and the
      control group comprised a total of 246 healthy volunteers. Trunk sway measures
      were performed using the Vertiguard-D device. With the device fixed by a belt at
      the hip (center of body mass), the subjects had to undergo 14 daily-life tasks
      under different sensorimotor conditions. Ankle sway was determined during the
      sensory organization test (SOT) on the BalanceMaster force plate in all patients
      by estimating the center of body mass from center of pressure changes within the
      plantar area. RESULTS: A nonlinear relationship between age and body sway was
      observed in majority of all the conditions. Furthermore, large sex-related
      differences in body sway were observed.The sensitivity of the mobile
      posturography was higher than determined during the SOT-force plate measurements
      or reported in literature before for state-of-the-art platform posturography.
      CONCLUSION: The present results indicate that the method introduced here can
      quantify postural deficits in a broad range and in an inhomogenous sample of
      patients.

PMID- 23151778
TI  - Ossiculoplasty in missing malleus and stapes patients:  experimental and
      preliminary clinical results with a new malleus replacement prosthesis with the
      otology-neurotology database.
AB  - OBJECTIVE: To present the preliminary results of new malleus replacement
      prosthesis combined with a total ossicular prosthesis in middle ear
      reconstruction in patients missing the malleus and stapes. STUDY DESIGN:
      Prospective experimental and nonrandomized clinical study. SETTING: Tertiary
      referral center. METHODS: An original titanium malleus replacement prosthesis
      (MRP) was designed to be inserted into the external auditory canal and to replace
      a missing malleus for various middle ear pathologies. The MRP was tested
      experimentally and clinically. The vibratory properties of the new prosthesis
      were measured using laser Doppler vibrometry. Ninety patients with missing
      malleus and stapes, undergoing 92 ossicular reconstructions were enrolled in this
      study from September 1994 to March 2012. Comparative analyses were made between a
      group of 34 cases of ossicular reconstructions with total prosthesis (TORP)
      positioned from the tympanic membrane to the stapes footplate (TM-to-footplate
      assembly) and a group of 58 cases of ossicular reconstructions with TORP
      positioned from a newly designed malleus replacement prosthesis (MRP) to the
      stapes footplate (MRP-to-footplate assembly). Preoperative and postoperative
      audiometric evaluation using conventional audiometry, that is, air-bone gap
      (ABG), bone-conduction thresholds (BC), and air-conduction thresholds (AC) were
      assessed. RESULTS: Experimentally, the vibratory properties of the MRP are
      promising and remain very good even when the MRP is cemented into the bony canal
      wall mimicking its complete osseous-integration, if this were to occur. This
      finding supports the short-term clinical results as in the TM-to-footplate group;
      the 3-month postoperative mean ABG was 23.3 dB compared with 12.5 dB in the MRP
      to-footplate group (difference, 10.8; 95% confidence interval, 4.0-17.6); 37.0%
      of patients from the TM-to-footplate group had a postoperative ABG of 10 dB or
      less, and 48.1% of patients had a postoperative ABG of 20 dB or less, as compared
      with 58.1% and 79.1%, respectively, in the MRP-to-footplate group. The average
      gain in AC was 11.0 dB in the TM-to-footplate group as compared with 21.3 dB in
      the MRP-to-footplate group (difference, -10.3; 95% confidence interval, -18.2 to 
      2.4). CONCLUSION: The results of this study indicate that superior postoperative
      hearing thresholds could be achieved using a MRP-to-footplate assembly, compared
      with a TM-to-footplate assembly in patients with an absent malleus undergoing
      ossiculoplasty. The postoperative AC thresholds, after 3 months and 1 year, are
      significantly lower in patients treated with the MRP-to-footplate assembly.

PMID- 23151779
TI  - Cochlear implantation rarely alters horizontal vestibulo-ocular reflex in
      motorized head impulse test.
AB  - OBJECTIVE: Determine the change in vestibular function in patients receiving a
      unilateral cochlear implant, and to compare these results with other signs and
      symptoms. STUDY DESIGN: Prospective cohort study. SETTING: Academic tertiary
      referral center. PATIENTS: Forty-four adults (mean age, 55 yr; range, 30-76 yr)
      receiving their first cochlear implant. INTERVENTION: Cochlear implantation. MAIN
      OUTCOME MEASURES: Horizontal high-frequency vestibulo-ocular reflex (VOR) was
      measured using the motorized head impulse rotator preoperatively and twice (on
      average two and 19 months) postoperatively. VOR gain and asymmetry were
      calculated (mean +/- standard deviation). Symptoms were assessed with a
      structured questionnaire. RESULTS: Gain on the operated side was 0.77 +/- 0.26
      preoperatively, 0.75 +/- 0.30 in the early and 0.73 +/- 0.33 in the late
      postoperative control, and did not change significantly. Mean asymmetry remained
      within 9% to 10% in all test occasions. Dizziness symptom score or dizziness
      related quality of life score did not change significantly. General quality-of
      life score improved significantly from that of preoperative 3.5 +/- 1.2 to that
      of 2.6 +/- 1.1 postoperatively (p = 0.01). Subjective hearing scores improved
      significantly from 4.9 +/- 0.3 to 2.4 +/- 1.0, respectively (p = 0.0000). Gain
      was decreased significantly in 4 patients (10%) in the early and in 2 patients
      (7%) in the late postoperative control. CONCLUSION: Late high-frequency loss of
      vestibular function or vestibular symptoms is rare but possible after cochlear
      implantation surgery. This should be taken into account in patient counseling
      especially when considering bilateral cochlear implant surgery.

PMID- 23151781
TI  - Etroplus suratensis (Bloch), the state fish of Kerala.

PMID- 23151782
TI  - The Sad paradox: mutations with dominant and recessive phenotypes.

PMID- 23151780
TI  - Endocannabinoid signalling is required for estrogen-dependent modulation of
      inhibitory transmission.

PMID- 23151783
TI  - Early modern natural history: contributions from the Americas and India.

PMID- 23151784
TI  - What history tells us XXIX. Transfers from plant biology: from cross protection
      to RNA interference and DNA vaccination.

PMID- 23151785
TI  - Crowding, molecular volume and plasticity: an assessment involving
      crystallography, NMR and simulations.
AB  - The discrepancy between the X-ray and NMR structures of Mycobacterium
      tuberculosis peptidyl-tRNA  hydrolase in relation to the functionally important
      plasticity of the molecule led to molecular dynamics simulations.  The X-ray and
      the NMR studies along with the simulations indicated an inverse correlation
      between crowding and molecular volume. A detailed comparison of proteins for
      which X-ray and the NMR structures appears to confirm this correlation. In
      consonance with the reported results of the investigations in cellular
      compartments and aqueous solution, the comparison indicates that the crowding
      results in compaction of the molecule as well as change in its shape, which could
      specifically involve regions of the molecule important in function. Crowding
      could thus influence the action of proteins through modulation of the
      functionally important plasticity of the molecule.

PMID- 23151786
TI  - Efficient multi-site-directed mutagenesis directly from genomic template.
AB  - In this article, the traditional multi-site-directed mutagenesis method based on
      overlap extension  PCR was improved specifically for complicated templates, such
      as genomic sequence or complementary DNA. This method was effectively applied for
      multi-site-directed mutagenesis directly from mouse genomic DNA, as well as for
      combination, deletion or insertion of DNA fragments.

PMID- 23151787
TI  - Transcription of gD and gI genes in BHV1-infected cells.
AB  - Glycoprotein D (gD) and glycoprotein I (gI) genes of bovine herpes virus 1 (BHV1)
      are contiguous genes with 141 bp region between the two open reading frames
      (ORFs). Expression of gD and gI from a bicistronic construct containing complete
      gD and gI gene has been reported either through internal ribosome entry site
      (IRES)-like element or through the scanning and leakage model (Mukhopadhyay
      2000). We here show by computational and experimental means that gD is expressed
      solely as bicistronic transcript comprising gD and gI coding region in BHV1
      infected cells. gI ORF was also shown to express separately. An IRES-like element
      was also predicted by IRES predicting software in the middle of the gD coding
      region; within that region a putative promoter was also identified by
      promoterscan. The intergenic region between the two ORF showed extensive
      secondary structure which brings the stop codon of gD very close to start codon
      of gI gene. gD gene transcript in BHV1-infected cells was solely bicistronic. gI
      transcript was also present in the BHV1-infected cells but in low copy number.
      The results indicate that gI is probably transcribed from its own transcript in
      BHV1-infected cells.

PMID- 23151788
TI  - Cx43, ZO-1, alpha-catenin and beta-catenin in cataractous lens epithelial cells.
AB  - Specimens of the anterior lens capsule with an attached monolayer of lens
      epithelial cells (LECs) were obtained from patients (n=52) undergoing cataract
      surgery. Specimens were divided into three groups based on the type of cataract:
      nuclear cataract, cortical cataract and posterior subcapsular cataract (PSC).
      Clear lenses (n=11) obtained from donor eyes were used as controls. Expression
      was studied by immunofluorescence, real-time PCR and Western blot. Statistical
      analysis was done using the student's t-test. Immunofluorescence results showed
      punctate localization of Cx43 at the cell boundaries in controls, nuclear
      cataract and PSC groups. In the cortical cataract group, cytoplasmic pools of
      Cx43 without any localization at the cell boundaries were observed. Real-time PCR
      results showed significant up-regulation of Cx43 in nuclear and cortical cataract
      groups. Western blot results revealed significant increase in protein levels of
      Cx43 and significant decrease of ZO-1 in all three cataract groups. Protein
      levels of alpha-catenin were decreased significantly in nuclear and cortical
      cataract group. There was no significant change in expression of beta-catenin in
      the cataractous groups. Our findings suggest that ZO-1 and alpha-catenin are
      important for gap junctions containing Cx43 in the LECs. Alterations in cell
      junction proteins may play a role during formation of different types of
      cataract.

PMID- 23151789
TI  - Comparative analysis of fecal microflora of healthy full-term Indian infants born
      with  different methods of delivery (vaginal vs cesarean): Acinetobacter sp.
      prevalence in vaginally born infants.
AB  - In this study fecal microflora of human infants born through vaginal delivery
      (VB) and through cesarean section (CB) were investigated using culture
      independent 16S rDNA cloning and sequencing approach. The results obtained
      clearly revealed that fecal microbiota of VB infants distinctly differ from those
      in their counterpart CB infants. The intestinal microbiota of infants delivered
      by cesarean section appears to be more diverse, in terms of bacteria species,
      than the microbiota of vaginally delivered infants. The most abundant bacterial
      species present in VB infants were Acinetobacter sp., Bifidobacterium sp. and
      Staphylococcus sp. However, CB infant's fecal microbiota was dominated with
      Citrobacter sp., Escherichia coli and Clostridium difficile. The intestinal
      microbiota of cesarean section delivered infants in this study was also
      characterized by an absence of Bifidobacteria species. An interesting finding of
      our study was recovery of large number of Acinetobacter sp. consisting of
      Acinetobacter pittii (former Acinetobacter genomic species 3), Acinetobacter
      junii and Acinetobacter baumannii in the VB infants clone library. Among these,
      Acinetobacter baumannii is a known nosocomial pathogen and Acinetobacter pittii
      (genomic species 3) is recently recognized as clinically important taxa within
      the Acinetobacter calcoaceticus-Acinetobacter baumannii (ACB) complex. Although
      none of the infants had shown any sign of clinical symptoms of disease, this
      observation warrants a closer look.

PMID- 23151790
TI  - Sialyl Lewis x expression in cervical scrapes of premalignant lesions.
AB  - Sialylated oligosaccharides of glycoproteins and glycolipids have been implicated
      in tumour progression and metastases. Altered expression of glycosidic antigens
      has been reported in cervical cancer. In cervix premalignant lesions, an
      increased expression of sialic acid has been reported. In the present study we
      determined the expression profiles of the glycosidic antigens Tn, sialyl Tn
      (sTn), Lewis a (Lea), sialyl Lewis a (sLea), Lewis x (Lex) and sialyl Lewis x
      (sLex) in cervical scrapes with cytological diagnoses of normal, low-grade
      squamous intraepithelial lesions (LGSIL) and highgrade squamous intraepithelial
      lesions (HGSIL). Cervical scrapings were collected to detect tumour antigens
      expressions by flow cytometry using monoclonal antibodies. Cytometry analysis of
      Tn, sTn, Lea and Lex did not reveal differences at the expression level among
      groups. The number of positive cells to sLea antigen increased in the HGSIL group
      with respect to the normal group (p=0.0495). The number of positive cells to sLex
      antigen in the samples increased with respect to the grade of squamous
      intraepithelial lesion (SIL) (p less than 0.001, Mann-Whitney U test). The
      intensity of expression of this antigen increased in the HGSIL samples with
      respect to normal samples (p less than 0.0068). sLex antigen could be a candidate
      to be used as biomarker for the early diagnosis of cervical cancer.

PMID- 23151791
TI  - Swainsonine promotes apoptosis in human oesophageal squamous cell carcinoma cells
      in vitro and in vivo through activation of mitochondrial pathway.
AB  - Swainsonine, a natural indolizidine alkaloid, has been reported to have
      antitumour effects, and can induce apoptosis in human gastric and lung cancer
      cells. In the present study, we evaluated the antitumour effects of swainsonine
      on several oesophageal squamous cell carcinoma cells and investigated relative
      molecular mechanisms. Swainsonine treatment inhibited the growth of Eca-109, TE-1
      and TE-10 cells in a concentration-dependent manner as measured by MTT assay.
      Morphological observation, DNA laddering detection and flow cytometry analysis
      demonstrated that swainsonine treatment induced Eca-109 cell apoptosis in vitro.
      Further results showed that swainsonine treatment up-regulated Bax, downregulated
      Bcl-2 expression, triggered Bax translocation to mitochondria, destructed
      mitochondria integrity and activated mitochondria-mediated apoptotic pathway,
      followed by the release of cytochrome c, which in turn activated caspase-9 and
      caspase-3, promoted the cleavage of PARP, resulting in Eca-109 cell apoptosis.
      Moreover, swainsonine treatment inhibited Bcl-2 expression, promoted Bax
      translocation, cytochrome c release and caspase-3 activation in xenograft tumour
      cells, resulting in a significant decrease of tumour volume and tumour weight in
      the swainsoninetreated xenograft mice groups compared with that in the control
      group. Taken together, this study demonstrated that swainsonine inhibited Eca-109
      cells growth through activation of mitochondria-mediated caspase-dependent
      pathway.

PMID- 23151792
TI  - Effects of diet-induced hypercholesterolemia on amyloid accumulation in
      ovariectomized mice.
AB  - A central hypothesis in the study of Alzheimer's disease (AD) is the accumulation
      and aggregation of  beta-amyloid peptide (A beta). Recent epidemiological studies
      suggest that patients with elevated cholesterol and decreased estrogen levels are
      more susceptible to AD through A beta accumulation. To test the above hypothesis,
      we used ovariectomized with diet-induced hypercholesterolemia (OVX) and
      hypercholesterolemia (HCL) diet alone mouse models. HPLC analysis reveals the
      presence of beta amyloid in the OVX and HCL mice brain. Congo red staining
      analysis revealed the extent of amyloid deposition in OVX and
      hypercholesterolemia mice brain. Overall, A beta levels were higher in OVX mice
      than in HCL. Secondly, estrogen receptors alpha (ER alpha) were assessed by
      immunohistochemistry and this suggested that there was a decreased expression of
      ER alpha in OVX animals when compared to hypercholesterolemic animals. A beta was
      quantified by Western blot and ELISA analysis. Overall, A beta levels were higher
      in OVX mice than in HCL mice. Our experimental results suggested that OVX animals
      were more susceptible to AD with significant increase in A beta peptide.

PMID- 23151795
TI  - Characteristic differences in metabolite profile in male and female plants of
      dioecious Piper betle L.
AB  - Piper betle is a dioecious pan-Asiatic plant having cultural and medicinal uses.
      It belongs to the family Piperaceae and is a native of the tropics although it is
      also cultivated in subtropical areas. Flowering in P. betle occurs only in
      tropical regions. Due to lack of inductive floral cycles the plant remains in its
      vegetative state in the subtropics. Therefore, due to lack of flowering, gender
      distinction cannot be made the in the subtropics. Gender distinction in P. betle
      in vegetative state can be made using Direct Analysis in Real Time Mass
      Spectroscopy (DARTMS), a robust highthroughput method. DARTMS analysis of leaf
      samples of two male and six female plants showed characteristic differences in
      the spectra between male and female plants. Semi-quantitative differences in some
      of the identified peaks in male and female landraces showed gender-based
      differences in metabolites. Cluster analysis using the peaks at m/z 151, 193, 235
      and 252 showed two distinct clusters of male and female landraces. It appears
      that male and female plants besides having flowers of different sexes also have
      characteristic differences in the metabolites representing two metabolic types.

PMID- 23151793
TI  - Identification and characterization of a gene encoding a putative
      lysophosphatidyl acyltransferase from Arachis hypogaea.
AB  - Lysophosphatidyl acyltransferase (LPAT) is the important enzyme responsible for
      the acylation of lysophosphatidic acid (LPA), leading to the generation of
      phosphatidic acid (PA) in plant. Its encoding gene is an essential candidate for
      oil crops to improve oil composition and increase seed oil content through
      genetic engineering. In this study, a full length AhLPAT4 gene was isolated via
      cDNA library screening and rapid amplification of cDNA ends (RACE); our data
      demonstrated that AhLPAT4 had 1631 nucleotides, encoding a putative 43.8 kDa
      protein with 383 amino acid residues. The deduced protein included a conserved
      acyltransferase domain and four motifs (I-IV) with putative LPA and acyl-CoA
      catalytic and binding sites. Bioinformatic analysis indicated that AhLPAT4
      contained four transmembrane domains (TMDs), localized to the endoplasmic
      reticulum (ER) membrane; detailed analysis indicated that motif I and motifs II
      III in AhLPAT4 were separated by the third TMD, which located on cytosolic and ER
      luminal side respectively, and hydrophobic residues on the surface of AhLPAT4
      protein fold to form a hydrophobic tunnel to accommodate the acyl chain.
      Subcellular localization analysis confirmed that AhLPAT4 was a cytoplasm
      protein.Phylogenetic analysis revealed that AhLPAT4 had a high homology (63.7
      78.3%) with putative LPAT4 proteins from Glycine max, Arabidopsis thaliana and
      Ricinus communis. AhLPAT4 was ubiquitously expressed in diverse tissues except in
      flower, which is almost undetectable. The expression analysis in different
      developmental stages in peanut seeds indicated that AhLPAT4 did not coincide with
      oil accumulation.

PMID- 23151796
TI  - Rates and pattern of ovule abortion vis-a-vis in situ pollen germination in some
      populations of Trifolium fragiferum L.
AB  - The present study is based on four populations of Trifolium fragiferum L. of the
      family Fabaceae growing at four different sites in Jammu region, India. The
      species, which grows as a common weed in the area of study, follows an annual
      life cycle of about three and a half months in the subtropical climates of Jammu
      region. While all of these populations were recorded in full bloom during
      February and March, they displayed a temporal scatter. Detailed studies revealed
      these population types to be morphologically similar but distinct in the many
      aspects studied. An interesting phenomenon noted for the plants of this species
      was in situ pollen germination, which was recorded in about 28.8 percent of the
      flowers studied. The species under investigation also showed an appreciable
      amount of ovule abortion. The ovule abortion in pistils was found to be non
      random, with the peduncular ovule aborting at a higher rate than the stylar one.
      The rates and patterns of ovule abortion were studied vis-a-vis in situ pollen
      germination and were compared between different populations. Interesting results
      were obtained, indicative of the fact that precocious pollen germination does
      affect the ovule abortion in one way or other.

PMID- 23151794
TI  - COCHLEATA controls leaf size and secondary inflorescence architecture via
      negative regulation of UNIFOLIATA (LEAFY ortholog) gene in garden pea Pisum
      sativum.
AB  - UNIFOLIATA [(UNI) or UNIFOLIATA-TENDRILLED ACACIA (UNI-TAC)] expression is known
      to be negatively regulated by COCHLEATA (COCH) in the differentiating stipules
      and flowers of Pisum sativum. In this study, additional roles of UNI and COCH in
      P. sativum were investigated. Comparative phenotyping revealed pleiotropic
      differences between COCH (UNI-TAC and uni-tac) and coch (UNI-TAC and uni-tac)
      genotypes of common genetic background. Secondary inflorescences were bracteole
      less and bracteolated in COCH and coch genotypes, respectively. In comparison to
      the leaves and corresponding sub-organs and tissues produced on COCH plants, coch
      plants produced leaves of 1.5-fold higher biomass, 1.5-fold broader petioles and
      leaflets that were 1.8-fold larger in span and 1.2-fold dorso-ventrally thicker.
      coch leaflets possessed epidermal cells 1.3-fold larger in number and size, 1.4
      fold larger spongy parenchyma cells and primary vascular bundles with 1.2-fold
      larger diameter. The transcript levels of UNI were at least 2-fold higher in coch
      leaves and secondary inflorescences than the corresponding COCH organs. It was
      concluded that COCH negatively regulated UNI in the differentiating leaves and
      secondary inflorescences and thereby controlled their sizes and/or structures. It
      was also surmised that COCH and UNI (LFY homolog) occur together widely in
      stipulate flowering plants.

PMID- 23151797
TI  - Aluminium localization and toxicity symptoms related to root growth inhibition in
      rice (Oryza sativa L.) seedlings.
AB  - We correlated root growth inhibition with aluminium (Al(3+)) localization and
      toxicity symptoms in rice roots using seedlings of two genotypes (tolerant and
      sensitive) that were exposed to different AlCl(3) concentrations. Al(3+)
      localization was evaluated by hematoxylin in primary roots and by morin in cross
      sections of the root tips. Neutral invertase enzyme activity and callose (1 -- 3,
      beta-D-glucan) accumulation were observed and compared with Al(3+) accumulation
      sites. Root growth was inhibited by Al(3+) in a concentration-specific manner and
      proportional to the increase of hematoxylin staining, being more pronounced in
      the sensitive genotype. Morin staining showed the presence of Al(3+) deep within
      the roots of the sensitive genotype, indicating that the metal was able to
      penetrate beyond the first few cell layers. In the tolerant genotype, Al(3+)
      penetration was restricted to the first two cell layers. Ruptures in exodermis
      and epidermis layers by lateral root protrusions in both genotypes allowed Al3+
      to enter into the roots. More intense activity of invertase in roots of the
      tolerant genotype was also observed, which could be related to greater root
      growth of this cultivar when submitted to Al(3+) stress. Moreover, Al(3+)-induced
      callose accumulation was a late response occurring in the same areas where Al(3+)
      was present.

PMID- 23151799
TI  - One hundred years of helicene chemistry. Part 1: non-stereoselective syntheses of
      carbohelicenes.
AB  - Carbohelicenes belong to a class of fascinating, chiral, and helicoidal
      molecules, which have a rich history in chemistry since the very beginning of the
      20th century. A renewed interest in polyaromatic chemistry and new synthetic
      challenges toward the search for innovative physical, biological, chemical and
      opto-electronic properties have brought high motivation in this field of studies.
      Theoretical insights gained from polyaromatic, chiral, conjugated and distorted
      pi-systems are also responsible for this development. Several synthetic avenues
      were originally reported for making lower helicenes, but for many years,
      photochemical synthesis has remained a major method for producing small amount of
      helicenes. High-dilution conditions is still a limiting factor in their
      synthesis. The fulgurous impact of organometallic chemistry, novel synthetic
      methods, and recent catalytic systems has promoted the development of helicene
      chemistry, toward a library of tailor-made and highly functionalized helicene
      molecules. Helicene chemistry is being considered as an expanding and modern
      field, leading to several applications in supramolecular chemistry, in
      nanosciences, in chemical-biology, in polymers and materials science. This first
      part of a series of three reviews on carbohelicenes will be devoted to a
      comprehensive report on non-stereoselective reactions and methods for producing
      helicenes, along with their functionalization.

PMID- 23151798
TI  - What in silico molecular docking can do for the 'bench-working biologists'.
AB  - Required by an increasing amount of scientists, the in silico docking field is in
      full expansion, new algorithms and methods appearing at an exponential rate. The
      sheer range of available programs is overwhelming for the benchworking biologist,
      which is often discouraging by the lack of a graphical user interface, good user
      manual or literature to validate a given program. This mini-review attempts to
      present the docking problem and available solutions from a non-bioinformatician
      point of view and makes a selection of the available servers and programs. These
      tools are evaluated from several points of view, as numbers of citations, ease of
      usage and computer requirements. Finally, the capabilities and limitations as
      well as specific applications of in silico docking techniques are presented.

PMID- 23151801
TI  - Sorcin modulates mitochondrial Ca(2+) handling and reduces apoptosis in neonatal
      rat cardiac myocytes.
AB  - Sorcin localizes in cellular membranes and has been demonstrated to modulate
      cytosolic Ca(2+) handling in cardiac myocytes. Sorcin also localizes in
      mitochondria; however, the effect of sorcin on mitochondrial Ca(2+) handling is
      unknown. Using mitochondrial pericam, we measured mitochondrial Ca(2+)
      concentration and fluxes in intact neonatal cardiac myocytes overexpressing
      sorcin. Our results showed that sorcin increases basal and caffeine-stimulated
      mitochondrial Ca(2+) concentration. This effect was associated with faster Ca(2+)
      uptake and release. The effect of sorcin was specific for mitochondria, since
      similar results were obtained with digitonin-permeabilized cells, where cytosolic
      Ca(2+) flux was disrupted. Furthermore, mitochondria of cardiac myocytes in which
      sorcin was overexpressed were more Ca(2+)-tolerant. Experiments analyzing
      apoptotic signaling demonstrated that sorcin prevented 2-deoxyglucose-induced
      cytochrome c release. Furthermore, sorcin prevented hyperglycemia-induced
      cytochrome c release and caspase activation. In contrast, antisense sorcin
      induced caspase-3 activation. Thus, sorcin antiapoptotic properties may be due to
      modulation of mitochondrial Ca(2+) handling in cardiac myocytes.

PMID- 23151802
TI  - Definitive evidence using enucleated cytoplasts for a nongenomic basis for the
      cystic change in endoplasmic reticulum structure caused by STAT5a/b siRNAs.
AB  - STAT5a/b species are well known as transcription factors that regulate nuclear
      gene expression. In a novel line of research in human pulmonary arterial
      endothelial cells (HPAECs), we previously observed that STAT5a associated with
      the Golgi apparatus and that siRNA-mediated knockdown of STAT5a/b led to the
      rapid development of a dramatic cystic change in the endoplasmic reticulum (ER)
      characterized by deposition along cyst membranes and tubule-to-cyst boundaries of
      the proteins reticulon-4 (RTN4; also called Nogo-B) and the ER-resident GTPase
      atlastin-3 (ATL3) and Golgi fragmentation. We now report that STAT5a can be
      observed in ER sheets in digitonin-permeabilized HPAECs and that anti-STAT5a
      cross- immunopanned ATL3 but not RTN4. Moreover, there was marked accumulation of
      the 63-kDa cytoskeleton-linking membrane protein and ER-spacer CLIMP63 (also
      called cytoskeleton-associated protein 4, CKAP4) and KDEL-mCherry within the
      cysts. That the STAT5a/b-siRNA-induced cystic ER phenotype developed in the
      presence of the transcription inhibitor 5,6-dichloro-1-beta-d
      ribofuranosylbenzimidazole (DRB) had suggested that the mechanism was independent
      of the transcription factor functions of STAT5a/b, i.e., was "nongenomic." We
      have now definitively tested the requirement for the nucleus in eliciting the
      STAT5a/b-siRNA-induced cystic ER phenotype. Enucleated HPAEC cytoplasts were
      prepared using adherent 35-mm cultures using the cytochalasin B-centrifugation
      method (typically yielding 65-75% enucleation). STAT5a/b siRNAs readily elicited
      the cystic ER phenotype including the marked luminal accumulation of CLIMP63 and
      Golgi fragmentation in the recovered HPAEC cytoplasts demonstrably lacking a
      nucleus. These studies provide unequivocal evidence using enucleated cytoplasts
      for a nongenomic mechanism(s) underlying the cystic change in ER structure
      elicited by STAT5a/b knockdown.

PMID- 23151804
TI  - Risk stratification for advanced colorectal neoplasia--letter.

PMID- 23151803
TI  - Regional distribution of SGLT activity in rat brain in vivo.
AB  - Na(+)-glucose cotransporter (SGLT) mRNAs have been detected in many organs of the
      body, but, apart from kidney and intestine, transporter expression, localization,
      and functional activity, as well as physiological significance, remain elusive.
      Using a SGLT-specific molecular imaging probe, alpha-methyl-4-deoxy-4
      [(18)F]fluoro-D-glucopyranoside (Me-4-FDG) with ex vivo autoradiography and
      immunohistochemistry, we mapped in vivo the regional distribution of functional
      SGLTs in rat brain. Since Me-4-FDG is not a substrate for GLUT1 at the blood
      brain barrier (BBB), in vivo delivery of the probe into the brain was achieved
      after opening of the BBB by an established procedure, osmotic shock. Ex vivo
      autoradiography showed that Me-4-FDG accumulated in regions of the cerebellum,
      hippocampus, frontal cortex, caudate nucleus, putamen, amygdala, parietal cortex,
      and paraventricular nucleus of the hypothalamus. Little or no Me-4-FDG
      accumulated in the brain stem. The regional accumulation of Me-4-FDG overlapped
      the distribution of SGLT1 protein detected by immunohistochemistry. In summary,
      after the BBB is opened, the specific substrate for SGLTs, Me-4-FDG, enters the
      brain and accumulates in selected regions shown to express SGLT1 protein. This
      localization and the sensitivity of these neurons to anoxia prompt the
      speculation that SGLTs may play an essential role in glucose utilization under
      stress such as ischemia. The expression of SGLTs in the brain raises questions
      about the potential effects of SGLT inhibitors under development for the
      treatment of diabetes.

PMID- 23151806
TI  - Expanding the reach of cancer metabolomics.
AB  - Metabolism is again emerging as a key property that differentiates normal cells
      from neoplastic tissues. The coupling of this phenomenon with advanced
      bioanalytic methods may now open new avenues for diagnostics in cancer via
      discovery of chemical biomarkers. In this issue of Cancer Prevention Research,
      Montrose and colleagues apply metabolic profiling to a model of chemically
      induced colorectal cancer and describe the metabolomic landscape of colorectal
      tumors and associated biofluids in great detail. Their analysis of plasma and
      fecal metabolites provides inroads into the noninvasive detection of colorectal
      cancer using biochemical markers, as some conserved metabolic changes were
      altered across tumors, plasma, and feces. Meanwhile, the specific alterations
      identified in this study offer insights into potential metabolic drivers of
      colorectal cancer. For example, elevated sarcosine and 2-hydroxyglutarate were
      detected in these induced tumors, implicating their respective metabolic pathways
      and downstream interactions in colorectal cancer progression. This work
      highlights the potential value of cancer metabolomics for the noninvasive
      analysis of colorectal neoplasias while underscoring the importance of profiling
      diverse sample sets and metabolites in relevant cancer models to identify and
      validate such findings.

PMID- 23151807
TI  - Mapping of three genetic determinants of susceptibility to estrogen-induced
      mammary cancer within the Emca8 locus on rat chromosome 5.
AB  - The ACI rat model of 17beta-estradiol (E2)-induced mammary cancer has gained wide
      use in the study of breast cancer etiology, prevention, and genetics. Emca8, a
      QTL that determines susceptibility to E2-induced mammary cancer, was previously
      mapped to rat chromosome 5 (RNO5) in an intercross between resistant Brown Norway
      (BN) and susceptible ACI rats. In this study, a panel of congenic rat strains,
      each of which carries BN alleles across a defined segment of RNO5 on the ACI
      genetic background, was generated and used to map more precisely the Emca8
      determinants of mammary cancer susceptibility. Three distinct genetic
      determinants were localized within Emca8, and two of these were mapped to
      intervals of less than 15 megabases. Emca8.1 harbors Cdkn2a, Cdkn2b, and other
      genes and is orthologous to the 9p21 breast cancer locus identified in genome
      wide and candidate gene association studies. Emca8.2 harbors Cdkn2c and other
      genes and is orthologous to the 1p32 locus in humans that is frequently deleted
      in breast cancers. Both Emca8.1 and Emca8.2 harbor copy number variants that are
      orthologous to copy number variant regions in humans. Gene expression profiles
      were defined for mammary tissues from E2-treated ACI and ACI.BN-Emca8 rats to
      define the impact of Emca8 on gene expression and identify differentially
      expressed genes residing within Emca8.1 and Emca8.2. This study further
      illustrates the relevance of the ACI rat model of E2-induced mammary cancer for
      identifying novel genetic determinants of breast cancer susceptibility and
      defining the mechanisms through which estrogens contribute to breast cancer
      development. Cancer Prev Res; 6(1); 59-69. (c)2012 AACR.

PMID- 23151808
TI  - Phase II study of the Src kinase inhibitor saracatinib (AZD0530) in metastatic
      melanoma.
AB  - BACKGROUND: Src kinases are activated in melanoma, and inhibition of Src kinase
      activity has pre-clinical anti-tumor effects. Targeting this pathway could
      therefore have therapeutic activity in patients with metastatic melanoma.
      PATIENTS AND METHODS: We conducted a multi-center, open-label study of the Src
      kinase inhibitor saracatanib (AZD0530) in patients with metastatic melanoma.
      Twenty-three patients received saracatanib at a dose of 175 mg daily. The primary
      objectives were to determine whether this agent had clinical activity in patients
      with advanced melanoma and whether it increased progression free survival.
      Functional effects on circulating T cells were also assessed. RESULTS: Twenty
      three patients received oral saracatanib on a continuous daily dosing regimen.
      There were no objective clinical responses. Saracatanib was generally well
      tolerated with few grade 3-4 adverse events. T cell function was inhibited in
      most patients, based on decreased superantigen-induced IL-2 production in post-
      versus pre-treatment samples. CONCLUSIONS: Saracatanib has minimal clinical
      activity as a single agent in an unselected population of patients with advanced
      melanoma, as evidenced by a lack of objective responses in this study. Reduced T
      cell cytokine production in most treated patients suggests potential immune
      suppressive activity by this agent.

PMID- 23151809
TI  - Inhibitory effects of Asterina pectinifera extracts on melanin biosynthesis
      through tyrosinase activity.
AB  - The control of melanogenesis is an important strategy in the treatment of
      abnormal skin pigmentation for cosmetic purposes. The aim of the present study
      was to investigate the anti-melanogenic effect of Asterina pectinifera (A.
      pectinifera) extracts by cell-free mushroom tyrosinase assay, cellular tyrosinase
      assay, melanin content assay and the analysis of related protein expression in
      melan-a cells. A. pectinifera was extracted with 80% methanol (80-MAP) and
      further fractionated with hexane (He-AP) and ethyl acetate (EA-AP). In addition,
      the enzyme extract (En-AP) of A. pectinifera, to which protease was added, was
      processed. EA-AP and En-AP among A. pectinifera extracts showed strong inhibitory
      activity against the cell-free mushroom tyrosinase activity. EA-AP and En-AP
      induced significant inhibition of melanin production and cellular tyrosinase
      activity. In the action of EA-AP and En-AP on melanogenesis, they reduced the
      expression of melanogenic genes and proteins including tyrosinase, tyrosinase
      related protein-1 (TRP-1) and dopachrome tautomerase (Dct). These results showed
      that EA-AP and En-AP inhibited melanogenesis by reducing tyrosinase activity and
      melanin production via subsequent downregulation of tyrosinase-related proteins.
      The overall results suggest that EA-AP and En-AP among A. pectinifera extracts
      may be promising candidates for the treatment of hyperpigmentation disorder and
      useful for self-tanning cosmetic products.

PMID- 23151810
TI  - Identification of a novel gene fusion RNF213-SLC26A11 in chronic myeloid leukemia
      by RNA-Seq.
AB  - Chronic myeloid leukemia (CML) was the first hematological malignancy to be
      associated with a specific genetic lesion. The Philadelphia translocation,
      producing a BCR-ABL hybrid oncogene, is the most common mechanism of CML
      development. However, in the present study, b3a2, b2a2 and ela2 fusion junctions
      of the breakpoint cluster region (BCR)-V-abl Abelson murine leukemia viral
      oncogene homolog 1 (ABL) gene were not detected in patients diagnosed with CML
      three and four years previously. RNA-Seq technology, with an average coverage of
      ~30-fold, was used to detect gene fusion events in a patient with a 6-year
      history of CML, identified to be in the chronic phase of the disease. Using
      deFuse and TopHat-fusion programs with improved filtering methods, we identified
      two reliable gene fusions in a blood sample obtained from the CML patient,
      including extremely low expression levels of the classic BCR-ABL1 gene fusion. In
      addition, a novel gene fusion involving the ring finger protein 213 (RNF213)
      solute carrier family 26, member 11 (SLC26A11) was identified and validated by
      reverse transcription polymerase chain reaction. Further bioinformatic analysis
      revealed that specific domains of SLC26A11 were damaged, which may affect the
      function of sulfate transportation of the normal gene. The present study
      demonstrated that, in specific cases, alternative gene fusions, besides BCR-ABL,
      may be associated with the development of CML.

PMID- 23151811
TI  - Characterization of the chimeric seven-transmembrane protein containing conserved
      region of helix C-F of microbial rhodopsin from Ganges River.
AB  - Proteorhodopsin (PR) is a light-driven proton pump that has been found in a
      variety of marine bacteria. Recently, many PR-like genes were found in non-marine
      environments. The goal of this study is to explore the function of rhodopsins
      that exist only as partial proteo-opsin genes using chimeras with marine green PR
      (GPR). We isolated nine partial genes of PR homologues using polymerase chain
      reaction (PCR) and chose three homologues of GPR from the surface of the Ganges
      River, which has earned them the name "CFR, Chimeric Freshwater Rhodopsin." In
      order to characterize the proteins, we constructed the cassette based on GPR
      sequence without helices C to F and inserted the isolated conserved partial
      sequences. When expressed in E. coli, we could observe light-driven proton
      pumping activity similar to proteorhodopsin, however, photocycle kinetics of CFRs
      are much slower than proteorhodopsin. Half-time decay of O intermediates of CFRs
      ranged between 143 and 333 ms at pH 10; their absorption maxima were between 515
      and 522 nm at pH 7. We can guess that the function of native rhodopsin, a retinal
      protein of fresh water bacteria, may be a light-driven proton transport based on
      the results from chimeric freshwater rhodopsins. This approach will enable many
      labs that keep reporting partial PCR-based opsin sequences to finally
      characterize their proteins.

PMID- 23151812
TI  - "Difficult-to treat" ulcers management: use of pulse dose radiofrequency.
AB  - AIM: In this paper we wanted to evaluate the impact of pain reduction on the
      evolution of "difficult-to treat" ulcers, using Radiofrequency analgesia in pulse
      dose modality. MATERIALS AND METHODS: We have performed a randomized trial to
      evaluate the efficacy of the RF in PD mode to reduce the healing time of ulcers
      of difficult management as outpatient for spontaneous and provoked pain. We
      enrolled 23 patients, including 7 males (30%) and 16 females (70%), aged between
      53 and 79 years (mean age = 67.2) sorted according to the first letter of the
      last name in ascending order and assigned alternately to one or another group.
      RESULTS: In Group A healing was obtained in 33% of patients (4/12), with an
      average healing time of 6 months while in Group B healing has been obtained in
      81% of patients (9/11) with an average time of 3 months (range 1-5 months)
      Student's T was performed to compare the average recovery time among the two
      groups; moreover we have analyzed the proportions of healed patients in the group
      A and B. DISCUSSION: Healing time significantly decreased in group B (p =
      0,013079). Even the cure rate has changed favorably, in a statistically
      significant way. CONCLUSIONS: According to the literature related to the use of
      the RF pulse dose, there is a greater effectiveness of this technique in respect
      of the classical PRF, in terms of immediate and long-term reduction of pain and
      this impacts positively on the course of ulcer healing.

PMID- 23151813
TI  - Meta-analysis of randomized trials comparing endoscopic stenting and surgical
      decompression for colorectal cancer obstruction.
AB  - PURPOSE: Surgical decompression is the traditional treatment for acute colorectal
      cancer obstruction. In recent years, colorectal stenting has been used to relieve
      the obstruction. This study used meta-analytic techniques to compare colonic
      stenting versus surgical decompression for colorectal cancer obstruction.
      METHODS: A comprehensive search of several databases was conducted. The search
      identified 321 potential abstracts and titles of which eight randomized trials
      involving 353 patients were retrieved in full text. A meta-analysis of the
      studies included was carried out to identify the differences in outcomes between
      the two procedures. RESULTS: The pooled analysis showed no significant
      differences for mortality (odds ratio (OR) 0.91) and morbidity (OR 2.05) rates
      between the two strategies while the permanent stoma creation rate was
      significantly higher in the surgical group as compared to the stent group (OR
      3.12). By comparing surgery and colonic stenting in studies which analyzed the
      use of stenting as a "bridge to surgery," the pooled analysis showed that primary
      anastomosis was more frequent in the stent group as compared to the surgical
      group (OR 0.42), and the stoma creation was more frequent in the surgical group
      as compared to the stent group (OR 2.36). CONCLUSION: Our study suggested that,
      in patients with acute colorectal cancer obstruction, stent placement improved
      several outcomes, such as primary anastomosis, stoma formation, and permanent
      stoma, while it failed to show an improvement in mortality and morbidity risk.

PMID- 23151814
TI  - The interplay between vacuolar and siderophore-mediated iron storage in
      Aspergillus fumigatus.
AB  - Iron is an essential element for all eukaryotes but its excess has deleterious
      effects. Aspergillus fumigatus produces extracellular siderophores for iron
      uptake and the intracellular siderophore ferricrocin (FC) for distribution and
      storage of iron. Iron excess has previously been shown to increase the content of
      ferric FC and the expression of the putative vacuolar iron importer CccA
      (AFUA_4G12530), indicating a role of both the vacuole and FC in iron
      detoxification. In this study, we show that CccA-deficiency decreases iron
      resistance in particular in combination with derepressed iron uptake, while
      overproduction of CccA increases iron resistance. Green fluorescence protein
      tagging confirmed localization of CccA in the vacuolar membrane. In contrast to
      CccA-deficiency, inactivation of FC biosynthesis did not affect iron resistance,
      which indicates that vacuolar rather than FC-mediated iron storage is the major
      iron detoxifying mechanism. After uptake, extracellular siderophore backbones are
      hydrolyzed and recycled. Lack of FC, CccA, and in particular lack of both
      increased the cellular content of iron chelated by siderophore breakdown
      products. These data indicate that the transfer of iron from extracellular
      siderophores to the metabolism, FC or the vacuole precedes recycling of
      siderophore breakdown products. Furthermore, this study indicates that CccA does
      not play an exclusive role in vacuolar iron storage for nutritional reuse.

PMID- 23151816
TI  - Barriers to warfarin use for stroke prevention in patients with atrial
      fibrillation in Hong Kong.
AB  - BACKGROUND: Oral anticoagulation medications such as warfarin reduce the risk of
      stroke in atrial fibrillation (AF) but have been underutilized. This study aimed
      to investigate physicians' perceptions of stroke prevention management and
      patients' knowledge of AF and warfarin therapy in Hong Kong (HK). HYPOTHESIS:
      Both physician and patient's knowledge on warfarin use were the barriers for
      stroke prevention in patients with atrial fibrillation in Hong Kong. METHODS:
      This prospective survey-based study was conducted between February 2011 and April
      2011 to assess physicians' perceptions of stroke prevention management, patients'
      knowledge of AF, and patients' knowledge of warfarin therapy. The results were
      scored and compared with those in foreign countries. RESULTS: Sixty-two
      physicians and 114 warfarin users were recruited in the study. The average score
      of HK physicians in the knowledge of stroke prevention therapy in AF patients was
      lower than that of Australian (AUS) family physicians (HK 2.48 vs AUS 4.02 out of
      7). The mean scores of AF patients in Hong Kong regarding the knowledge of AF
      were lower than that of United Kingdom (UK) (HK 1.16 vs UK 2.24 out of 4) (P <
      0.001) and that of Finland (FIN) (HK 2.77 vs FIN 5.94 out of 8) (P < 0.001),
      respectively. The mean score of AF patients in Hong Kong regarding the knowledge
      of warfarin therapy was lower than that of AF patients in the United States (US)
      (HK 2.39 vs US 3.92). CONCLUSIONS: The barriers of warfarin use for AF patients
      in Hong Kong were related to both physicians and patients. Many Hong Kong
      physicians did not comply with international recommendations of stroke prevention
      in AF patients, and AF patients had a low knowledge level about the disease and
      warfarin therapy.

PMID- 23151817
TI  - Cardiopulmonary exercise test predicts sustained ventricular arrhythmias in
      chronic heart failure.
AB  - BACKGROUND: The cardiopulmonary exercise test (CPX) is an affordable tool for
      risk prediction in patients with chronic heart failure (CHF). We aimed to
      determine the role of CPX parameters in predicting the risk of incidence of
      sustained ventricular arrhythmias (SVA) in CHF. METHODS: Sixty-one consecutive
      patients with CHF enrolled in the Daunia Heart Failure Registry underwent CPX and
      were followed for 327 +/- 247 days. Clinical follow-up was performed every month
      and anticipated in case of re-hospitalisation for cardiac disease. Incidence of
      SVA was evaluated by direct clinical examination (ECG, ambulatory ECG). RESULTS:
      Patients with episodes of SVA (N 14) showed lower values of pVO2 and PetCO2, and
      higher values of VE/VCO2, VE/VCO2 slope, and VE%. After correction for age,
      gender, diabetes, ischaemic heart disease and left ventricular ejection fraction,
      peak VO2 (hazard ratio (HR) 0.68, 95 % confidence interval (CI) 0.51-0.91, p <
      0.05), VE% (HR 1.38, 95 % CI 1.04-1.84, p < 0.05), VE/VCO2 (HR 1.38, 95 % CI 1.04
      1.82, p < 0.05), VE/VCO2 slope (HR 1.77, 95 % CI 1.31-2.39, p < 0.01), PetCO2 (HR
      0.66, 95 % CI 0.50-0.88, p < 0.01) were found as predictors of SVA. At Kaplan
      Meier analysis, lower event-free rates were found in subjects with peak VO2
      values below median (log rank p < 0.05), values of VE/VCO2 above mean (p < 0.05),
      higher VE/VCO2 slope tertiles (p <0.05), and values of PetCO2 below median (p <
      0.05). CONCLUSIONS: CPX provides prognostic independent information for risk of
      SVA in subjects with CHF.

PMID- 23151818
TI  - NF-kappaB activation by equine arteritis virus is MyD88 dependent and promotes
      viral replication.
AB  - NF-kappaB, a family of transcription factors involved in different cell functions
      and immune responses is targeted by viruses. The mechanism of NF-kappaB
      signalling and its role in replication of EAV have not been investigated. We
      demonstrate that EAV infection in BHK-21 cells activates NF-kappaB, and this
      activation was found to be mediated through the MyD88 pathway. Infection of
      IKKbeta(-/-) murine embryo fibroblasts (MEFs), which are deficient in NF-kappaB
      signalling, resulted in lower virus titre, less cytopathic effect, and reduced
      expression of viral proteins. These findings implicate the MyD88 pathway in EAV
      induced NF-kappaB activation and suggest that NF-kappaB activation is essential
      for efficient replication of EAV.

PMID- 23151819
TI  - Phylogenetic analysis of porcine epidemic diarrhea virus field strains prevailing
      recently in China.
AB  - Porcine epidemic diarrhea virus (PEDV) is the causative agent of porcine epidemic
      diarrhea (PED), which is characterized by severe diarrhea, dehydration and high
      mortality in the affected pigs. Recently, clinical outbreaks of diarrhea in
      suckling piglets emerged in pig-producing areas of China. In this study,
      molecular detection of PEDV was conducted using RT-PCR (targeting the M gene) on
      samples collected from piglets with watery diarrhea from 15 pig farms, and
      phylogenetic analysis of PEDV field strains was carried out based on their M and
      S genes. In addition, the complete genome sequence of a PEDV field strain was
      determined. PEDV was detected in 92.7 % of the samples (267/288). The 15 M genes
      that were amplified shared 99.6-100 % nucleotide identity and 99.1-100 % amino
      acid similarity with each other. The 15 S genes exhibited 98.6-99.9 % homology,
      both at the nucleotide level and at the deduced amino acid level. Phylogenetic
      analysis showed that all of the amplified M genes grouped in cluster 3, together
      with some Chinese, Korean and Thai strains, while all of the amplified S genes
      were in cluster 3 and were closely related to Korean strains. Compared with
      previous PEDV strains, all of the S genes have common characteristics, namely, a
      4-aa (GENQ) insertion between positions 55 and 56, a 1-aa (N) insertion between
      positions 135 and 136, and a 2-aa (DG) deletion between positions 155 and 156,
      similar or identical to Korean KNU-serial strains reported in recent years. The
      genome of the sequenced PEDV field strain is 28,038 nucleotides in length,
      excluding the poly (A) tail. Our findings suggest that a novel PEDV with a
      characteristic variant S gene is responsible for recent outbreaks of clinical
      diarrhea in piglets in China.

PMID- 23151821
TI  - Proof of concept of MRI-guided tracked radiation delivery: tracking one
      dimensional motion.
AB  - In radiotherapy one aims to deliver a radiation dose to a tumour with high
      geometrical accuracy while sparing organs at risk (OARs). Although image guidance
      decreases geometrical uncertainties, treatment of cancer of abdominal organs is
      further complicated by respiratory motion, requiring intra-fraction motion
      compensation to fulfil the treatment intent. With an ideal delivery system, the
      optimal method of intra-fraction motion compensation is to adapt the beam
      collimation to the moving target using a dynamic multi-leaf collimator (MLC)
      aperture. The many guidance strategies for such tracked radiation delivery tested
      up to now mainly use markers and are therefore invasive and cannot deal with
      target deformations or adaptations for OAR positions. We propose to address these
      shortcomings using the online MRI guidance provided by an MRI accelerator and
      present a first step towards demonstration of the technical feasibility of this
      proposal. The position of a phantom subjected to one-dimensional (1D) periodic
      translation was tracked using a fast 1D MR sequence. Real-time communication with
      the MR scanner and control of the MLC aperture were established. Based on the
      time-resolved position of the phantom, tracked radiation delivery to the phantom
      was realized. Dose distributions for various delivery conditions were recorded on
      a gafchromic film. Without motion a sharply defined dose distribution is
      obtained, whereas considerable blur occurs for delivery to a moving phantom. With
      compensation for motion, the sharpness of the dose distribution is nearly
      restored. The total latency in our motion management architecture is
      approximately 200 ms. Combination of the recorded phantom and aperture positions
      with the planned dose distribution enabled the reconstruction of the delivered
      dose in all cases, which illustrates the promise of online dose accumulation and
      confirms that latency compensation could further enhance our results. For a
      simple 1D tracked delivery scenario, the technical feasibility of MRI-guided
      tracked radiation delivery is confirmed. More generic tracking scenarios require
      advanced MRI, leading to increased acquisition time and more challenging image
      processing problems. Latency compensation is therefore an important subject of
      future investigations.

PMID- 23151822
TI  - Heterosis and combining ability for body weight in a diallel cross of three
      chicken genotypes.
AB  - The aim of the study was to evaluate heterotic and combining ability effects for
      growth in nine chicken genotypes. A 3 * 3 complete diallel mating system
      involving two indigenous breeds named Venda (V) and Naked Neck (N) and one
      commercial broiler breed named Ross 308 (R) were used. The nine genetic groups of
      crosses were reared up from hatch to 13 weeks of age in deep litter open house.
      Body weights of 180 chicks (20 chicks per genetic group), recorded at 0, 3, 5, 7,
      9, 11, and 13 weeks of age, were used to estimate heterosis, general combining
      ability (GCA), and specific combining ability (SCA). Results showed that the Ross
      308 had the heaviest body weight at all weeks of measurement except for hatch.
      With respect to crosses, the V * R and its reciprocal cross, R * V had the
      heaviest body weights at 13 weeks. Heterosis estimates for body weight were
      higher in the Venda male * Ross 308 female and Venda male and Naked Neck female
      crosses. GCA was significant (P <= 0.01) for body weight from hatch to 13 weeks
      of age while SCA and reciprocal effects were both significant (P <= 0.05) for
      body weight at all ages of measurement except for hatch. The Ross 308 gave the
      highest positive effect of GCA for body weight except for hatch. V * N gave the
      highest and positive effects of SCA for body weight.

PMID- 23151820
TI  - Persuasive system design does matter: a systematic review of adherence to web
      based interventions.
AB  - BACKGROUND: Although web-based interventions for promoting health and health
      related behavior can be effective, poor adherence is a common issue that needs to
      be addressed. Technology as a means to communicate the content in web-based
      interventions has been neglected in research. Indeed, technology is often seen as
      a black-box, a mere tool that has no effect or value and serves only as a vehicle
      to deliver intervention content. In this paper we examine technology from a
      holistic perspective. We see it as a vital and inseparable aspect of web-based
      interventions to help explain and understand adherence. OBJECTIVE: This study
      aims to review the literature on web-based health interventions to investigate
      whether intervention characteristics and persuasive design affect adherence to a
      web-based intervention. METHODS: We conducted a systematic review of studies into
      web-based health interventions. Per intervention, intervention characteristics,
      persuasive technology elements and adherence were coded. We performed a multiple
      regression analysis to investigate whether these variables could predict
      adherence. RESULTS: We included 101 articles on 83 interventions. The typical web
      based intervention is meant to be used once a week, is modular in set-up, is
      updated once a week, lasts for 10 weeks, includes interaction with the system and
      a counselor and peers on the web, includes some persuasive technology elements,
      and about 50% of the participants adhere to the intervention. Regarding
      persuasive technology, we see that primary task support elements are most
      commonly employed (mean 2.9 out of a possible 7.0). Dialogue support and social
      support are less commonly employed (mean 1.5 and 1.2 out of a possible 7.0,
      respectively). When comparing the interventions of the different health care
      areas, we find significant differences in intended usage (p=.004), setup
      (p<.001), updates (p<.001), frequency of interaction with a counselor (p<.001),
      the system (p=.003) and peers (p=.017), duration (F=6.068, p=.004), adherence
      (F=4.833, p=.010) and the number of primary task support elements (F=5.631,
      p=.005). Our final regression model explained 55% of the variance in adherence.
      In this model, a RCT study as opposed to an observational study, increased
      interaction with a counselor, more frequent intended usage, more frequent updates
      and more extensive employment of dialogue support significantly predicted better
      adherence. CONCLUSIONS: Using intervention characteristics and persuasive
      technology elements, a substantial amount of variance in adherence can be
      explained. Although there are differences between health care areas on
      intervention characteristics, health care area per se does not predict adherence.
      Rather, the differences in technology and interaction predict adherence. The
      results of this study can be used to make an informed decision about how to
      design a web-based intervention to which patients are more likely to adhere.

PMID- 23151823
TI  - Dynamic contrast-enhanced MR imaging of carotid atherosclerotic plaque: model
      selection, reproducibility, and validation.
AB  - PURPOSE: To compare four known pharmacokinetic models for their ability to
      describe dynamic contrast material-enhanced magnetic resonance (MR) imaging of
      carotid atherosclerotic plaques, to determine reproducibility, and to validate
      the results with histologic findings. MATERIALS AND METHODS: The study was
      approved by the institutional medical ethics committee. Written informed consent
      was obtained from all patients. Forty-five patients with 30%-99% carotid stenosis
      underwent dynamic contrast-enhanced MR imaging. Plaque enhancement was measured
      at 16 time points at approximately 25-second image intervals by using a
      gadolinium-based contrast material. Pharmacokinetic parameters (volume transfer
      constant, K(trans); extracellular extravascular volume fraction, v(e); and blood
      plasma fraction, v(p)) were determined by fitting a two-compartment model to
      plaque and blood gadolinium concentration curves. The relative fit errors and
      parameter uncertainties were determined to find the most suitable model. Sixteen
      patients underwent imaging twice to determine reproducibility. Carotid
      endarterectomy specimens from 16 patients who were scheduled for surgery were
      collected for histologic validation. Parameter uncertainties were compared with
      the Wilcoxon signed rank test. Reproducibility was assessed by using the
      coefficient of variation. Correlation with histologic findings was evaluated with
      the Pearson correlation coefficient. RESULTS: The mean relative fit uncertainty
      (+/-standard error) for K(trans) was 10% +/- 1 with the Patlak model, which was
      significantly lower than that with the Tofts (20% +/- 1), extended Tofts (33% +/-
      3), and extended graphical (29% +/- 3) models (P < .001). The relative
      uncertainty for v(p) was 20% +/- 2 with the Patlak model and was significantly
      higher with the extended Tofts (46% +/- 9) and extended graphical (35% +/- 5)
      models (P < .001). The reproducibility (coefficient of variation) for the Patlak
      model was 16% for K(trans) and 26% for v(p). Significant positive correlations
      were found between K(trans) and the endothelial microvessel content determined on
      histologic slices (Pearson rho = 0.72, P = .005). CONCLUSION: The Patlak model is
      most suited for describing carotid plaque enhancement. Correlation with
      histologic findings validated K(trans) as an indicator of plaque
      microvasculature, and the reproducibility of K(trans) was good.

PMID- 23151824
TI  - Nonselective transarterial chemoperfusion: a palliative treatment for malignant
      pleural mesothelioma.
AB  - PURPOSE: To evaluate tumor response by means of volumetric assessment, survival,
      and changes in patient symptoms after the treatment of unresectable and/or
      recurrent pleural mesothelioma by using regional nonselective transarterial
      chemoperfusion as a palliative treatment option. MATERIALS AND METHODS: This
      retrospective study was approved by the hospital ethical committee, and all
      patients signed an informed consent prior to treatment. Thirty-nine patients
      (mean age, 64.0 years; 10 women and 29 men) with unresectable pleural
      mesothelioma were treated with repetitive transarterial chemoperfusion between
      March 2007 and March 2010, with a mean of 2.9 sessions per patient at 4-week
      intervals. Transarterial chemoperfusion was performed by using mitomycin C,
      cisplatin, and gemcitabine. Computed tomography findings and patient symptoms
      were evaluated. Tumor response was evaluated by using Response Evaluation
      Criteria in Solid Tumors guidelines, and survival was assessed with the Kaplan
      Meier method. The change in volume for the partial-response group was tested by
      using the Wilcoxon signed-rank test. RESULTS: In 36% of treated tumors (14 of
      39), partial response was achieved, and tumor volume decreased from a mean value
      +/- standard deviation of 839.6 mL +/- 590.3 (range, 3.9-1972.2 mL) to 137 mL +/-
      399.8 (range, 0.88-1131.4; P = .00012). In 49% of tumors (19 of 39), stable
      disease was noted. In 15% of tumors (six of 39), progressive disease was seen.
      Mean specific growth rate of the tumor was 0.00158% per day. The mean survival
      time was 14.2 months (range, 2.1-33.1 months) from the start of treatment. For
      patients with tumors that responded to treatment, mean survival time was 15
      months (range, 4.5-33.1 months). Mean time to disease progression was 2.6 months
      for all tumors, 1.5 months for stable disease, and 1.3 months for progressive
      disease. CONCLUSION: Transarterial chemoperfusion may have the potential to yield
      positive results and response in the treatment of recurrent and/or unresectable
      pleural mesothelioma. (c) RSNA, 2012.

PMID- 23151825
TI  - Regional and global biventricular function in pulmonary arterial hypertension: a
      cardiac MR imaging study.
AB  - PURPOSE: To determine whether chronic pulmonary arterial pressure (PAP) elevation
      affects regional biventricular function and whether regional myocardial function
      may be reduced in pulmonary arterial hypertension (PAH) patients with preserved
      global right ventricular (RV) function. MATERIALS AND METHODS: After informed
      consent, 35 PAH patients were evaluated with right heart catheterization and
      cardiac magnetic resonance (MR) imaging and compared with 13 healthy control
      subjects. Biventricular segmental, section, and mean ventricular peak systolic
      longitudinal strain (E(LL)), as well as left ventricular (LV) circumferential and
      RV tangential strains were compared between PAH patients and control subjects and
      correlated with global function and catheterization of the right heart indexes.
      Spearman rho correlation with Bonferroni correction was used. Multiple linear
      regression analysis was performed to determine predictors for regional myocardial
      function. RESULTS: In the RV of PAH patients, longitudinal contractility was
      reduced at the basal, mid, and apical levels, and tangential contractility was
      reduced at the midventricular level. Mean RV E(LL) positively correlated with
      mean PAP (r = 0.62, P < .0014) and pulmonary vascular resistance index (PVRI) (r
      = 0.77, P < .0014). Mean PAP was a predictor of mean RV E(LL) (beta = .19, P =
      .005) in a multiple linear regression analysis. In the LV, reduced LV
      longitudinal and circumferential contractility were noted at the base. LV
      anteroseptal E(LL) positively correlated with increased mean PAP (r = 0.5, P =
      .03) and septal eccentricity index (r = 0.5, P = .01). In a subgroup of PAH
      patients with normal global RV function, significantly reduced RV longitudinal
      contractility was noted at basal and mid anterior septal insertions, as well as
      the mid anterior RV wall (P < .05 for all). CONCLUSION: In PAH patients, reduced
      biventricular regional function is associated with increased RV afterload (mean
      PAP and PVRI). Cardiac MR imaging helps identify regional RV dysfunction in PAH
      patients with normal global RV function. SUPPLEMENTAL MATERIAL:
      http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.12111599/-/DC1.

PMID- 23151826
TI  - Progressive supranuclear palsy: high-field-strength MR microscopy in the human
      substantia nigra and globus pallidus.
AB  - PURPOSE: To characterize changes in the magnetic resonance (MR) relaxation
      properties of progressive supranuclear palsy (PSP) and tissue from neurologically
      normal brains by using high-resolution (21.1-T, 900-MHz) MR microscopy of
      postmortem human midbrain and basal ganglia. MATERIALS AND METHODS: This HIPAA
      compliant study was approved by the institutional review board at the Mayo Clinic
      and informed consent was obtained. Postmortem tissue from age-matched PSP (n = 6)
      and control (n = 3) brains was imaged by using three-dimensional fast low-angle
      shot MR imaging with isotropic resolution of 50 MUm. Relaxation times and
      parametric relaxation maps were generated from spin-echo and gradient-recalled
      echo sequences. MR findings were correlated with histologic features by
      evaluating the presence of iron by using Prussian blue and ferritin and microglia
      burden as determined by a custom-designed color deconvolution algorithm. T2 and
      T2*, signal intensities, percent pixels (that could not be fitted in a pixel-by
      pixel regression analysis due to severe hypointensity), and histologic data
      (total iron, ferritin, and microglia burden) were statistically analyzed by using
      independent sample t tests (P < .05). RESULTS: PSP specimens showed higher iron
      burden in the cerebral peduncles and substantia nigra than did controls. However,
      only the putamen was significantly different, and it correlated with a decrease
      of T2* compared with controls (-48%; P = .043). Similarly, substantia nigra
      showed a significant decrease of T2* signal in PSP compared with controls (-57%;
      P = .028). Compared with controls, cerebral peduncles showed increased T2 (38%; P
      = .026) and T2* (34%; P = .014), as well as higher T2 signal intensity (57%; P =
      .049). Ferritin immunoreactivity was the opposite from iron burden and was
      significantly lower compared with controls in the putamen (-74%; P = .025), red
      nucleus (-61%; P = .018), and entire basal ganglia section (-63%; P = .016).
      CONCLUSION: High-field-strength MR microscopy yielded pronounced differences in
      substantia nigra and globus pallidus of PSP compared with control brains.
      Histologic data also suggested that the predominant iron in PSP is hemosiderin,
      not ferritin. Iron in the brain is a contrast enhancer and potential biomarker
      for PSP.

PMID- 23151827
TI  - Mild cognitive impairment: cerebrospinal fluid tau biomarker pathologic levels
      and longitudinal changes in white matter integrity.
AB  - PURPOSE: To evaluate the relationship between (a) pathologic levels of
      cerebrospinal fluid (CSF) total tau as an index of the intensity of ongoing
      neuronal degeneration and (b) longitudinal changes in white matter (WM) integrity
      in patients with mild cognitive impairment (MCI). MATERIALS AND METHODS:
      Participants gave written informed consent, and the Norwegian committee for
      medical research ethics approved the study. Thirty patients with MCI and
      nonpathologic CSF total tau levels, nine patients with MCI and pathologic CSF
      total tau levels, and 16 age-matched healthy control subjects underwent diffusion
      tensor imaging at baseline and after a mean follow-up of 2.6 years +/- 0.54
      (standard deviation), with range of 1.58-3.98 years. The effect of diagnosis (MCI
      vs no MCI) at baseline and CSF tau levels at fractional anisotropy (FA), mean
      diffusivity, radial diffusivity (D(R)), and axial diffusivity were tested with
      tract-based spatial statistics. Differences in WM integrity at baseline and
      follow-up and change over time were compared among patients with pathologic CSF
      total tau levels (MCI high tau), patients with normal CSF total tau levels (MCI
      low tau), and healthy control subjects. Linear mixed-model between-group within
      subject analyses were conducted to examine differences in rate of change over
      time in FA and D(R). RESULTS: Longitudinal analysis of regional WM change
      revealed significant decrease in FA (P = .038) and increase in D(R) (P = .018) in
      the MCI high-tau group relative to control subjects. For D(R), the changes were
      regionally specific to the right cingulum and the right superior and inferior
      longitudinal fasciculi. CONCLUSION: Reduction in WM integrity was greater in
      patients with MCI who had the most intense neuronal degeneration as indexed by
      using CSF total tau, suggesting that these patients might represent a subgroup of
      MCI with more intense WM degeneration who are possibly at greater risk of
      developing Alzheimer disease.

PMID- 23151828
TI  - Evaluation of adrenal metastases from renal cell carcinoma and hepatocellular
      carcinoma: use of delayed contrast-enhanced CT.
AB  - PURPOSE: To retrospectively compare absolute and relative washout of adrenal
      metastases in patients with renal cell carcinoma (RCC) and hepatocellular
      carcinoma (HCC) to that of adrenal adenoma. MATERIALS AND METHODS: Between
      November 1994 and August 2011, in this institutional review board-approved study
      (with waiver of informed consent), 16 patients with 19 adrenal metastases (16 in
      13 RCC patients, three in three HCC patients) and 20 patients with 21 adrenal
      adenomas (16 in 15 RCC patients, five in five HCC patients) underwent dedicated
      adrenal protocol consisting of unenhanced, 1-minute contrast material-enhanced,
      and 15-minute delayed contrast-enhanced computed tomography (CT). The attenuation
      values and percentage enhancement washout, including absolute percentage washout
      (APW) and relative percentage washout (RPW), were calculated. If available,
      histologic findings and the change in the size of adrenal lesions were assessed.
      Statistical analyses were performed by using generalized estimating equation and
      coefficient of variation. RESULTS: The mean APW of the metastases (observer 1,
      67% +/- 11 [standard deviation]; observer 2, 63% +/- 12) was not significantly
      different from that of adenomas (observer 1, 73% +/- 9; observer 2, 72% +/- 12)
      for observer 1 (P = .143) and was significantly different for observer 2 (P =
      .029). The mean RPW of the metastases (observer 1, 46% +/- 11; observer 2, 43% +/
      12) was significantly lower than that of adenomas (observer 1, 62% +/- 19;
      observer 2, 60% +/- 17) (all P < .001 for each observer). With a threshold of 60%
      for APW or 40% for RPW, 95% (18 of 19) and 89% (17 of 19), respectively, of the
      metastases were falsely diagnosed as lipid-poor adenomas by each observer. All
      nine metastases that were followed up at CT had a substantial growth in size.
      CONCLUSION: In patients with RCC and HCC who undergo dedicated adrenal CT imaging
      for known adrenal lesions, the percentage enhancement washout of adrenal
      metastases is similar to that of lipid-poor adrenal adenomas. Careful imaging
      follow-up or pathologic tissue confirmation is needed.

PMID- 23151829
TI  - Assessment of primary colorectal cancer heterogeneity by using whole-tumor
      texture analysis: contrast-enhanced CT texture as a biomarker of 5-year survival.
AB  - PURPOSE: To determine if computed tomographic (CT) texture features of primary
      colorectal cancer are related to 5-year overall survival rate. MATERIALS AND
      METHODS: Institutional review board waiver was obtained for this retrospective
      analysis. Texture features of the entire primary tumor were assessed with
      contrast material-enhanced staging CT studies obtained in 57 patients as part of
      an ethically approved study and by using proprietary software. Entropy,
      uniformity, kurtosis, skewness, and standard deviation of the pixel distribution
      histogram were derived from CT images without filtration and with filter values
      corresponding to fine (1.0), medium (1.5, 2.0), and coarse (2.5) textures.
      Patients were followed up until death and were censored at 5 years if they were
      still alive. Kaplan-Meier analysis was performed to determine the relationship,
      if any, between CT texture and 5-year overall survival rate. The Cox proportional
      hazards model was used to assess independence of texture parameters from stage.
      RESULTS: Follow-up data were available for 55 of 57 patients. There were eight
      stage I, 19 stage II, 17 stage III, and 11 stage IV cancers. Fine-texture feature
      Kaplan-Meier survival plots for entropy, uniformity, kurtosis, skewness, and
      standard deviation of the pixel distribution histogram were significantly
      different for tumors above and below each respective threshold receiver operating
      characteristic (ROC) curve optimal cutoff value (P = .001, P = .018, P = .032, P
      = .008, and P = .001, respectively), with poorer prognosis for ROC optimal values
      (a) less than 7.89 for entropy, (b) at least 0.01 for uniformity, (c) less than
      2.48 for kurtosis, (d) at least -0.38 for skewness, and (e) less than 61.83 for
      standard deviation. Multivariate Cox proportional hazards regression analysis
      showed that each parameter was independent from the stage predictor of overall
      survival rate (P = .001, P = .009, P = .006, P = .02, and P = .001,
      respectively). CONCLUSION: Fine-texture features are associated with poorer 5
      year overall survival rate in patients with primary colorectal cancer.
      SUPPLEMENTAL MATERIAL:
      http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.12120254/-/DC1.

PMID- 23151830
TI  - Head and neck squamous cell carcinoma: diagnostic performance of diffusion
      weighted MR imaging for the prediction of treatment response.
AB  - PURPOSE: To determine the diagnostic performance of diffusion-weighted (DW)
      imaging for the prediction of treatment failure in primary head and neck squamous
      cell carcinoma (HNSCC). MATERIALS AND METHODS: The study was approved by the
      local institutional ethics committee and conducted with informed written consent
      in patients with primary HNSCC treated with radiation therapy and chemotherapy.
      DW imaging of the primary tumor was performed before treatment in 37 patients and
      was repeated within 2 weeks of treatment in 30 patients. Histograms of apparent
      diffusion coefficients (ADCs) were analyzed, and mean ADC, kurtosis, skewness,
      and their respective percentage change were correlated for local failure and
      local control at 2 years by using the Student t test. Univariate and multivariate
      analyses of the ADC parameters, T stage, and tumor volume were performed by using
      logistic regression for prediction of local failure. RESULTS: Local failure
      occurred in 16 of 37 (43%) patients and local control occurred in 21 of 37 (57%)
      patients. Pretreatment ADC parameters showed no correlation with local failure.
      There was significant intratreatment increase in mean ADC and a decrease in
      skewness and kurtosis (P < .001, P < .001, P = .024, respectively) for the whole
      group of patients when compared with those before treatment. During treatment,
      primary tumors showed a significantly lower increase in percentage change of mean
      ADC, higher skewness, and higher kurtosis for local failure than for local
      control (P = .016, .015, and .040, respectively). These ADC parameters also were
      significant for predicting local failure with use of univariate but not
      multivariate analysis. CONCLUSION: Early intratreatment DW imaging has the
      potential to allow prediction of treatment response at the primary site in
      patients with HNSCC.

PMID- 23151831
TI  - Efficacy of computer-aided detection as a second reader for 6-9-mm lesions at CT
      colonography: multicenter prospective trial.
AB  - PURPOSE: To assess the effect of computer-aided detection (CAD) as a second
      reader on the sensitivity and specificity of computed tomographic (CT)
      colonography in detecting 6-9-mm colorectal cancer (CRC) lesions. MATERIALS AND
      METHODS: Individuals with clinical indications for colonoscopy--either for
      symptoms or as part of participating in a surveillance program or CRC screening-
      were prospectively enrolled at one of 10 academic centers between July 2007 and
      May 2009. Institutional review board approval was obtained at each clinical site,
      and all participants provided written informed consent. All participants
      underwent CT colonography and colonoscopy on the same day. Experienced readers
      interpreted the CT colonography images unassisted and then reviewed all
      colorectal lesion-like structures pinpointed by the CAD algorithm. Segmental
      unblinding of CT colonoscopy findings at colonoscopy was utilized. The
      sensitivity and specificity of unassisted and CAD-assisted reading in identifying
      individuals with 6-9-mm lesions were calculated and compared by means of pairwise
      analysis. RESULTS: A total of 618 participants (mean age, 57.9 years; 54.5% male)
      were included in the final analysis. Of these participants, 464 (75.1%) had no
      lesions 6 mm or larger, and 52 (8.4%) had 6-9-mm lesions. The sensitivity of CT
      colonography with unassisted reading and that with CAD-assisted reading in
      identifying individuals with 6-9-mm lesions was 65.4% (95% confidence interval
      [CI]: 50.9%, 78.0%) and 76.9% (95% CI: 63.2%, 87.5%; P = .016), respectively. No
      significant change in specificity was observed: The specificity of CT
      colonography with unassisted and that with CAD-assisted reading was 91.8% (95%
      CI: 88.9%, 94.1%) and 90.9% (95% CI: 88.0%, 93.4%; P = .063), respectively.
      Evaluation of CAD candidates required an additional 1.6 minutes (25th-75th
      percentile: 1.0 minute to 3.4 minutes). CONCLUSION: The addition of CAD to
      reading performed by experienced readers resulted in a significant benefit in the
      detection of 6-9-mm polyps at CT colonography in this cohort. SUPPLEMENTAL
      MATERIAL: http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.12120376/
      /DC1.

PMID- 23151832
TI  - SLCO2B1 c.935G>A single nucleotide polymorphism has no effect on the
      pharmacokinetics of montelukast and aliskiren.
AB  - OBJECTIVE: A nonsynonymous single nucleotide polymorphism (SNP) in the SLCO2B1
      gene encoding organic anion transporting polypeptide 2B1 (OATP2B1), c.935G>A
      (p.R312Q; rs12422149), has been associated with reduced plasma concentrations of
      montelukast in patients with asthma. Our aim was to examine the possible effects
      of the SLCO2B1 c.935G>A SNP on the single-dose pharmacokinetics of the suggested
      OATP2B1 substrates montelukast and aliskiren. METHODS: Sixteen healthy volunteers
      with the SLCO2B1 c.935GG genotype, 12 with the c.935GA genotype, and five with
      the c.935AA genotype ingested a single 10 mg dose of montelukast or a 150 mg dose
      of aliskiren, with a washout period of 1 week. Plasma montelukast concentrations
      were measured up to 24 h. Plasma and urine aliskiren concentrations were measured
      up to 72 and 12 h, respectively, and plasma renin activity up to 24 h after
      aliskiren intake. RESULTS: The SLCO2B1 genotypes had no significant effect on the
      pharmacokinetics of montelukast or aliskiren. The geometric mean ratios with 90%
      confidence intervals of montelukast area under the plasma concentration-time
      curve from 0 h to infinity (AUC(0-infinity)) in participants with the c.935GA or
      the c.935AA genotype to those with the c.935GG genotype were 1.02 (0.87, 1.21) or
      0.88 (0.71, 1.10), respectively (P=0.557). The geometric mean ratios (90%
      confidence interval) of aliskiren AUC(0-infinity) in participants with the
      c.935GA or the c.935AA genotype to those with the c.935GG genotype were 0.98
      (0.74, 1.30) or 1.24 (0.85, 1.80), respectively (P=0.576). CONCLUSION: These data
      do not support the suggested functional significance of the SLCO2B1 c.935G>A SNP
      on OATP2B1 activity in vivo.

PMID- 23151833
TI  - Postoperative facial nerve function in pediatric parotidectomy: a 12-year review.
AB  - OBJECTIVE: To analyze the incidence of postparotidectomy facial nerve dysfunction
      in pediatric patients and to evaluate the association between patient
      demographics or underlying pathology and functional outcomes. STUDY DESIGN: Case
      series with chart review. SETTING: Tertiary-care pediatric hospital. SUBJECTS AND
      METHODS: We reviewed charts of patients younger than 18 years who underwent
      parotidectomy performed by a pediatric otolaryngologist between 1999 and 2011 at
      a tertiary pediatric center. Distributions of postoperative facial nerve
      dysfunction and timing of recovery were noted. Chi-square and t-test analyses
      were conducted to determine the association between demographics or pathology and
      functional outcomes. RESULTS: Forty-three patients met inclusion criteria: 41
      underwent superficial parotidectomy, and 2 underwent total parotidectomy. Leading
      indications for surgery were atypical mycobacterial infection (16/43 [37.2%]) and
      first branchial cleft anomaly (8/43 [18.6]). The facial nerve was sacrificed in 1
      (2%) patient with Ewing's sarcoma involving the nerve. The incidence of immediate
      facial nerve paresis was 21% (9/43), involving the marginal mandibular nerve (n =
      7), buccal branch (n = 1), and both marginal mandibular and frontal branches (n =
      1). Full recovery of nerve function in patients with paresis occurred within 1
      month (n = 2), 2 months (n = 1), 6 months (n = 3), or 10 months (n = 2).
      CONCLUSION: Postparotidectomy paresis of distal branches of the facial nerve is a
      common occurrence in the pediatric population and should be discussed during
      preoperative evaluation. The risk is comparable to that of the adult population.
      Age, gender, and pathologic diagnosis were not predictive of postoperative nerve
      dysfunction.

PMID- 23151834
TI  - Interaural differences of distortion product otoacoustic emission amplitudes in
      patients with unilateral tinnitus.
AB  - OBJECTIVE: We aimed to determine whether abnormalities in outer hair cell (OHC)
      function were related to tinnitus through interaural comparison of distortion
      product otoacoustic emissions (DPOAEs). STUDY DESIGN: Cross-sectional study.
      SETTING: Tertiary care university teaching hospital. PARTICIPANTS: Twenty-seven
      patients with unilateral tinnitus and pure-tone average of both ears <= 25 dB
      hearing loss (HL) at 500, 1000, 2000, and 4000 Hz were included. SUBJECTS AND
      METHODS: Pure-tone thresholds observed at 500 to 16,000 Hz and DPOAE amplitudes
      at f2 frequencies of 1001 to 6348 Hz were compared between the tinnitus ears and
      nontinnitus ears in patients with unilateral tinnitus. RESULTS: The pure-tone
      averages (13 +/- 6 dB HL) in the nontinnitus ears were similar to those (15 +/- 6
      dB HL) in the tinnitus ears. There were no differences in pure-tone averages at
      all frequencies tested. While the DPOAE amplitudes measured at f2 frequencies of
      1001 to 3174 Hz in tinnitus ears were not different from those in the nontinnitus
      ears, the tinnitus ears showed significantly reduced DPOAE amplitudes when
      compared with the nontinnitus ears at frequencies of 4004 to 6348 Hz. CONCLUSION:
      OHC dysfunction was correlated with tinnitus at high frequencies, and DPOAE
      amplitudes can provide additional information about cochlear dysfunction, which
      is complementary to pure-tone audiometry.

PMID- 23151835
TI  - Heterotopic ossification and delayed foreign body reaction after hyoid suspension
      for obstructive sleep apnea.

PMID- 23151837
TI  - Health-related quality of life and psychological states in patients with
      pulmonary arterial hypertension.
AB  - BACKGROUND: Pulmonary arterial hypertension (PAH) is a chronic illness that
      impairs physical function and leads to right-sided heart failure and premature
      death. There is limited knowledge on health-related quality of life (HRQOL) and
      psychological states in patients with PAH. OBJECTIVE: The aim of this study was
      to determine the HRQOL and the psychological states of patients with PAH along
      with predictors of HRQOL. METHODS: In a cross-sectional design, participants with
      PAH completed the Medical Outcomes Study Short Form-36 v2 to measure generic
      HRQOL, the US Cambridge Pulmonary Hypertension Outcome Review to measure disease
      specific HRQOL, and the Profile of Mood States to measure the psychological
      states. Descriptive statistics were used to calculate all sociodemographic and
      clinical data and were expressed as means and standard deviations for continuous
      variables and as frequencies and proportions for dichotomous and nominal
      variables. The statistical significance level was set at P < 0.05. A multiple
      linear regression analysis was performed to examine the sociodemographic and
      clinical variables as predictors of HRQOL. A bivariate analysis of the
      sociodemographic and clinical variables was performed to determine correlates
      with HRQOL. The variables that correlated with HRQOL at the 0.20 level of
      significance were included. RESULTS: There were 149 participants, 127 women and
      22 men, with a mean age of 53.5 years. The participants demonstrated diminished
      general health, physical functioning, role physical, and vitality on the Short
      Form-36 v2. Functional class, education level, oxygen use, years since diagnosis,
      and calcium channel blocker therapy were predictive of poorer HRQOL. CONCLUSIONS:
      Patients with PAH are experiencing diminished physical health and HRQOL. Future
      studies are needed to design and test interventions to improve HRQOL.

PMID- 23151836
TI  - Patient perspectives about depressive symptoms in heart failure: a review of the
      qualitative literature.
AB  - BACKGROUND: Scientists have systematically established the prevalence and the
      consequences of depressive symptoms in patients with heart failure (HF). However,
      a comprehensive understanding of patient perspectives about depressive symptoms,
      in combination with HF, has not been published. A patient-centered approach may
      support the design of interventions that are effective and acceptable to patients
      with HF and depressive symptoms. OBJECTIVE: The aim of this study was to review
      qualitative findings about patient perspectives of contributing factors,
      associated symptoms, consequences, and self-care strategies used for depressive
      symptoms in HF. METHODS: Qualitative studies were included if they were published
      between 2000 and 2012, if they were in English, and if they described emotional
      components about living with HF. Three electronic databases were searched using
      the key words heart failure, qualitative, and depression or psychosocial or
      stress or emotional. RESULTS: Thirteen studies met the inclusion criteria.
      Patients with HF reported that financial stressors, overall poor health, past
      traumatic life experiences, and negative thinking contributed to depressive
      symptoms. The patients described cognitive-affective symptoms of depression and
      anxiety but not somatic symptoms of depression. Perceived consequences of
      depressive symptoms included hopelessness, despair, impaired social
      relationships, and a decreased ability to engage in HF self-care. Recommended
      management strategies consisted of enhanced social support and cognitive
      strategies. CONCLUSIONS: Depressive symptoms in patients with HF were associated
      with a number of contributing factors, including those not specifically related
      to their disease, and serious consequences that reduced their self-care ability.
      Nonpharmacological management approaches to depressive symptoms that include
      improved social support or cognitive interventions may be effective and
      acceptable strategies.

PMID- 23151838
TI  - Effects of wetland recovery on soil labile carbon and nitrogen in the Sanjiang
      Plain.
AB  - Soil management significantly affects the soil labile organic factors.
      Understanding carbon and nitrogen dynamics is extremely helpful in conducting
      research on active carbon and nitrogen components for different kinds of soil
      management. In this paper, we examined the changes in microbial biomass carbon
      (MBC), microbial biomass nitrogen (MBN), dissolved organic carbon (DOC), and
      dissolved organic nitrogen (DON) to assess the effect and mechanisms of land
      types, organic input, soil respiration, microbial species, and vegetation
      recovery under Deyeuxia angustifolia freshwater marshes (DAMs) and recovered
      freshwater marsh (RFM) in the Sanjiang Plain, Northeast China. Identifying the
      relationship among the dynamics of labile carbon, nitrogen, and soil
      qualification mechanism using different land management practices is therefore
      important. Cultivation and land use affect intensely the DOC, DON, MBC, and MBN
      in the soil. After DAM soil tillage, the DOC, DON, MBC, and MBN at the surface of
      the agricultural soil layer declined significantly. In contrast, their recovery
      was significant in the RFM surface soil. A long time was needed for the
      concentration of cultivated soil total organic carbon and total nitrogen to be
      restored to the wetland level. The labile carbon and nitrogen fractions can reach
      a level similar to that of the wetland within a short time. Typical wetland
      ecosystem signs, such as vegetation, microbes, and animals, can be recovered by
      soil labile carbon and nitrogen fraction restoration. In this paper, the D.
      angustifolia biomass attained natural wetland level after 8 years, indicating
      that wetland soil labile fractions can support wetland eco-function in a short
      period of time (4 to 8 years) for reconstructed wetland under suitable
      environmental conditions.

PMID- 23151839
TI  - Bioluminescent enzymatic rapid assay of water integral toxicity.
AB  - A bioluminescent rapid method was developed to estimate the integral toxicity of
      natural and wastewater. This method is based on registering the effect of the
      polluted water sample on the parameters of the bioluminescent reaction catalyzed
      by the multi-component reagent containing NADH:FMN oxidoreductase, luciferase,
      and their substrates co-immobilized in a starch carrier. Several ways to increase
      the method's sensitivity to toxic substances were suggested; conditions were
      selected to make it possible to determine, with maximum efficiency, the content
      of toxic substances corresponding to a certain maximum permissible concentration.
      The sensitivity of soluble and immobilized coupled enzymatic systems to a series
      of organic pollutants (phenols, quinones, and salts of heavy metals) was
      compared. It was shown that the reagent is the most sensitive to the effect of
      phenols and quinones. The method was tested during analysis of the wastewater
      from a pulp and paper plant and can be used for biotesting in both laboratory and
      field conditions.

PMID- 23151840
TI  - Colorectal cancer associated with abdominal aortic aneurysm: results of EVAR
      followed by colectomy.
AB  - The association of colorectal cancer and abdominal aortic aneurysm (AAA) is
      infrequent but poses special problems of priority of treatment under elective
      circumstances. The purpose of this study was to retrospectively evaluate the
      outcome of 16 consecutive patients undergoing endovascular aneurysm repair (EVAR)
      followed by colectomy. Operative mortality was nil. Operative morbidity included
      two transient rise of serum creatinine level and one extraperitoneal anastomotic
      leakage which evolved favourably with conservative treatment. EVAR allowed a very
      short delay of treatment of colorectal cancer after aneurysm repair, minimizing
      operative complications.

PMID- 23151841
TI  - Synthesis and post-polymerisation modifications of aliphatic poly(carbonate)s
      prepared by ring-opening polymerisation.
AB  - Owing to their low toxicity, biocompatibility and biodegradability, aliphatic
      poly(carbonate)s have been widely studied as materials for biomedical
      application. Furthermore, the synthetic versatility of the six-membered cyclic
      carbonates for the realization of functional degradable polymers by ring-opening
      polymerisation has driven wider interest in this area. In this review, the
      synthesis and ring-opening polymerisation of functional cyclic carbonates that
      have been reported in the literature in the past decade are discussed. Finally,
      the post-polymerisation modification methods that have been applied to the
      resulting homopolymers and copolymers and the application of the materials are
      also discussed.

PMID- 23151842
TI  - Early salvage radiation therapy combined with short-term hormonal therapy in
      recurrent prostate cancer after radical prostatectomy: single-institution 4-year
      data on outcome, toxicity, health-related quality of life and co-morbidities from
      184 consecutive patients treated with 70 Gy.
AB  - The aim of this study was to investigate the role of 70 Gy salvage radiotherapy
      (SRT) combined with short-term neoadjuvant hormonal therapy (NHT) in the
      treatment of recurrent disease after radical prostatectomy (RP), and to consider
      quality of life (QoL), survival outcomes and impact of co-morbidities on
      treatment-related rectal-genitourinary toxicity. Electronic records of 184 SRT
      patients treated consecutively between October 2001 and February 2007 were
      analyzed. Median age was 64 years (median follow-up 48 months). NHT was given to
      165 patients (median 3 months). Pre-RP and pre-SRT PSA, PSA doubling time,
      Gleason score (GS), seminal vesicle invasion (SVI) and detectable post-SRT PSA
      were recorded. Any detectable PSA or PSA >0.1 ng/ml + nadir was considered
      biochemical failure (BcF). The Charlson co-morbidity index was used to correlate
      co-morbidities and rectal-genitourinary toxicity. Scores from the health-related
      QoL EORTC QLQ-C30 and PR-25 questionnaires were also evaluated. In 116 (63%)
      patients, a long-lasting curative effect was indicated by undetectable PSA
      levels. In univariate analysis, using BcF as an outcome variable, p<0.001 was
      found for GS, pre-SRT PSA, SVI and detectable post-SRT PSA. Multivariate analysis
      showed p=0.01 for SVI, p=0.09 for GS, and detectable post-SRT PSA (p=0.01); with
      metastases as an outcome variable, only SVI was significant (p=0.007). Cancer
      specific and overall survival were 99 and 95%, respectively. Although microscopy
      showed SVI or GS 8-10 in the prostatectomy specimens 17/40 (43%) and 13/29 (45%),
      respectively, of patients still showed undetectable PSA at long-term follow-up
      (median 55 months) after SRT. Likewise, 11/31 (36%) patients with pre-SRT PSA
      >1.0 ng/ml and 80/134 (60%) patients with PSA doubling time (PSADT) <10 still
      showed undetectable PSA after 50 months. Slightly elevated acute and late rectal
      genitourinary grade 3-4 toxicity was observed. No association with co
      morbidity/toxicity was found. EORTC QLQ-C30 scores were similar to or slightly
      better than reference values. SRT with 70 Gy combined with 3-month NHT results in
      long-term undetectable PSA in >50% of patients with recurrence after RP with
      acceptable rectal-genitourinary toxicity and without negatively affecting long
      term QoL. Non-metastatic patients should not be disqualified from receiving SRT
      although presenting with poor prognostic factors at surgery.

PMID- 23151844
TI  - The next step in brain tumor classification: "Let us now praise famous men"... or
      molecules?

PMID- 23151843
TI  - Neurotrophin-4 is more potent than brain-derived neurotrophic factor in
      promoting, attracting and suppressing geniculate ganglion neurite outgrowth.
AB  - The geniculate ganglion, which provides innervation to taste buds in the anterior
      tongue and palate, is unique among sensory ganglia in that its neurons depend on
      both neurotrophin-4 (NT4) and brain-derived neurotrophic factor (BDNF) for
      survival. Whereas BDNF is additionally implicated in taste axon guidance at
      targeting stages, much less is known about the guidance role of NT4 during
      targeting, or about either neurotrophin during initial pathfinding. NT4 and BDNF
      have distinct expression patterns in vivo, raising the possibility of distinct
      roles. We characterized the influence of NT4 and BDNF on geniculate neurites in
      collagen I gels at early embryonic through postnatal stages. During early
      pathfinding to the tongue (embryonic days 12-13; E12-13), NT4 and BDNF promote
      significantly longer outgrowth than during intralingual targeting (E15-18). NT4
      is more potent than BDNF at stimulating neurite outgrowth and both factors
      exhibit concentration optima, i.e. intermediate concentrations (0.25 ng/ml NT4 or
      25 ng/ml BDNF) promote maximal neurite extension and high concentrations (10
      ng/ml NT4 or 200 ng/ml BDNF) suppress it. Only partial suppression was seen at
      E12 (when axons first emerge from the ganglion in vivo) and postnatally, but
      nearly complete suppression occurred from E13 to E18. We show that cell death is
      not responsible for suppression. Although blocking the p75 receptor reduces
      outgrowth at the optimum concentrations of NT4 and BDNF, it did not reduce
      suppression of outgrowth. We also report that NT4, like BDNF, can act as a
      chemoattractant for geniculate neurites, and that the tropic influence is
      strongest during intralingual targeting (E15-18). NT4 does not appear to act as
      an attractant in vivo, but it may prevent premature invasion of the epithelium by
      suppressing axon growth.

PMID- 23151845
TI  - Toll-like receptor activation during cutaneous allergen sensitization blocks
      development of asthma through IFN-gamma-dependent mechanisms.
AB  - Toll-like receptors (TLRs) are pattern-recognition receptors that have a pivotal
      role as primary sensors of microbial products and as initiators of innate and
      adaptive immune responses. We investigated the role of TLR2, TLR3, and TLR4
      activation during cutaneous allergen sensitization in the modulation of allergic
      asthma. The results show that dermal exposure to TLR4 ligand lipopolysaccharide
      (LPS) or TLR2 ligand Pam3Cys suppresses asthmatic responses by reducing airway
      hyperreactivity, mucus production, Th2-type inflammation in the lungs, and IgE
      antibodies in serum in a dose-dependent manner. In contrast, TLR3 ligand
      Poly(I:C) did not protect the mice from asthmatic symptoms but reduced IgE and
      induced IgG2a in serum. LPS (especially) and Pam3Cys enhanced the activation of
      dermal dendritic cell (DCs) by increasing the expression of CD80 and CD86 but
      decreased DC numbers in draining lymph nodes at early time points. Later, these
      changes in DCs led to an increased number of CD8(+) T cells and enhanced the
      production of IFN-gamma in bronchoalveolar lavage fluid. In conclusion, dermal
      exposure to LPS during sensitization modulates the asthmatic response by skewing
      the Th1/Th2 balance toward Th1 by stimulating the production of IFN-gamma. These
      findings support the hygiene hypothesis and pinpoint the importance of dermal
      microbiome in the development of allergy and asthma.

PMID- 23151846
TI  - miR-137 inhibits the invasion of melanoma cells through downregulation of
      multiple oncogenic target genes.
AB  - MicroRNAs are small noncoding RNAs that regulate gene expression and have
      important roles in various types of cancer. Previously, miR-137 was reported to
      act as a tumor suppressor in different cancers, including malignant melanoma. In
      this study, we show that low miR-137 expression is correlated with poor survival
      in stage IV melanoma patients. We identified and validated two genes (c-Met and
      YB1) as direct targets of miR-137 and confirmed two previously known targets,
      namely enhancer of zeste homolog 2 (EZH2) and microphthalmia-associated
      transcription factor (MITF). Functional studies showed that miR-137 suppressed
      melanoma cell invasion through the downregulation of multiple target genes. The
      decreased invasion caused by miR-137 overexpression could be phenocopied by small
      interfering RNA knockdown of EZH2, c-Met, or Y box-binding protein 1 (YB1).
      Furthermore, miR-137 inhibited melanoma cell migration and proliferation.
      Finally, miR-137 induced apoptosis in melanoma cell lines and decreased BCL2
      levels. In summary, our study confirms that miR-137 acts as a tumor suppressor in
      malignant melanoma and reveals that miR-137 regulates multiple targets including
      c-Met, YB1, EZH2, and MITF.

PMID- 23151848
TI  - Serum response factor controls transcriptional network regulating epidermal
      function and hair follicle morphogenesis.
AB  - Serum response factor (SRF) is a transcription factor that regulates the
      expression of growth-related immediate-early, cytoskeletal, and muscle-specific
      genes to control growth, differentiation, and cytoskeletal integrity in different
      cell types. To investigate the role for SRF in epidermal development and
      homeostasis, we conditionally knocked out SRF in epidermal keratinocytes. We
      report that SRF deletion disrupted epidermal barrier function leading to early
      postnatal lethality. Mice lacking SRF in epidermis displayed morphogenetic
      defects, including an eye-open-at-birth phenotype and lack of whiskers. SRF-null
      skin exhibited abnormal morphology, hyperplasia, aberrant expression of
      differentiation markers and transcriptional regulators, anomalous actin
      organization, enhanced inflammation, and retarded hair follicle (HF) development.
      Transcriptional profiling experiments uncovered profound molecular changes in SRF
      null E17.5 epidermis and revealed that many previously identified SRF target CArG
      box-containing genes were markedly upregulated in SRF-null epidermis, indicating
      that SRF may function to repress transcription of a subset of its target genes in
      epidermis. Remarkably, when transplanted onto nude mice, engrafted SRF-null skin
      lacked hair but displayed normal epidermal architecture with proper expression of
      differentiation markers, suggesting that although keratinocyte SRF is essential
      for HF development, a cross-talk between SRF-null keratinocytes and the
      surrounding microenvironment is likely responsible for the barrier-deficient
      mutant epidermal phenotype.

PMID- 23151847
TI  - Gene profiling of narrowband UVB-induced skin injury defines cellular and
      molecular innate immune responses.
AB  - The acute response of human skin to UVB radiation has not been fully
      characterized. We sought to define the cutaneous response at 24 hours following
      narrowband UVB (NB-UVB, 312-nm peak), a therapeutically relevant source of UVB,
      using transcriptional profiling, immunohistochemistry, and immunofluorescence.
      There were 1,522 unique differentially regulated genes, including upregulated
      genes encoding antimicrobial peptides (AMPs) (S100A7, S100A12, human beta
      defensin 2, and elafin), as well as neutrophil and monocyte/dendritic cell (DC)
      chemoattractants (IL-8, CXCL1, CCL20, CCL2). Ingenuity pathway analysis
      demonstrated activation of innate defense and early adaptive immune pathways.
      Immunohistochemistry confirmed increased epidermal staining for AMPs (S100A7,
      S100A12, human beta-defensin 2, and elafin). Inflammatory myeloid CD11c(+)BDCA1(
      ) DCs were increased in irradiated skin, which were immature as shown by minimal
      colocalization with DC-LAMP, and coexpressed inflammatory markers tumor necrosis
      factor (TNF) and TNF-related apoptosis-inducing ligand in irradiated skin. There
      were increased BDCA3(+) DCs, a cross-presenting DC subtype with immunosuppressive
      functions, and these cells have not been previously characterized as part of the
      response to UVB. These results show that the acute response of human skin to
      erythemogenic doses of NB-UVB includes activation of innate defense mechanisms,
      as well as early infiltration of multiple subtypes of inflammatory DCs, which
      could serve as a link between innate and adaptive immunity.

PMID- 23151850
TI  - Hair steroid profiling reveals racial differences in male pattern baldness
      between Korean and Caucasian populations.

PMID- 23151851
TI  - Quantitative assessment of regional cerebral blood flow by dynamic susceptibility
      contrast-enhanced MRI, without the need for arterial blood signals.
AB  - In dynamic susceptibility contrast-enhanced magnetic resonance imaging (DSC-MRI),
      an arterial input function (AIF) is usually obtained from a time-concentration
      curve (TCC) of the cerebral artery. This study was aimed at developing an
      alternative technique for reconstructing AIF from TCCs of multiple brain regions.
      AIF was formulated by a multi-exponential function using four parameters, and the
      parameters were determined so that the AIF curves convolved with a model of
      tissue response reproduced the measured TCCs for 20 regions. Systematic
      simulations were performed to evaluate the effects of possible error sources. DSC
      MRI and positron emission tomography (PET) studies were performed on 14 patients
      with major cerebral artery occlusion. Cerebral blood flow (CBF) images were
      calculated from DSC-MRI data, using our novel method alongside conventional AIF
      estimations, and compared with those from (15)O-PET. Simulations showed that the
      calculated CBF values were sensitive to variations in the assumptions regarding
      cerebral blood volume. Nevertheless, AIFs were reasonably reconstructed for all
      patients. The difference in CBF values between DSC-MRI and PET was -2.2 +/- 7.4
      ml/100 g/min (r = 0.55, p < 0.01) for our method, versus -0.2 +/- 8.2 ml/100
      g/min (r = 0.47, p = 0.01) for the conventional method. The difference in the
      ratio of affected to unaffected hemispheres between DSC-MRI and PET was 0.07 +/-
      0.09 (r = 0.82, p < 0.01) for our method, versus 0.07 +/- 0.09 (r = 0.83, p <
      0.01) for the conventional method. The contrasts in CBF images from our method
      were the same as those from the conventional method. These findings suggest the
      feasibility of assessing CBF without arterial blood signals.

PMID- 23151849
TI  - CD8(+) T cells mediate RAS-induced psoriasis-like skin inflammation through IFN
      gamma.
AB  - The RAS signaling pathway is constitutively activated in psoriatic keratinocytes.
      We expressed activated H-RAS(V12G) in suprabasal keratinocytes of adult mice and
      observed rapid development of a psoriasis-like skin phenotype characterized by
      basal keratinocyte hyperproliferation, acanthosis, hyperkeratosis, intraepidermal
      neutrophil microabscesses, and increased T helper type 1 (Th1)/Th17 and T cell
      type 1 (Tc1)/Tc17 skin infiltration. The majority of skin-infiltrating CD8(+) T
      cells coexpressed IFN-gamma and IL-17A. When RAS was expressed on a Rag1-/-
      background, microabscess formation, inducible nitric oxide synthase expression,
      and keratinocyte hyperproliferation were suppressed. Depletion of CD8(+), but not
      CD4(+), T cells reduced cutaneous and systemic inflammation, the RAS-induced
      increase in cutaneous Th17 and IL-17(+) gammadelta T cells, and epidermal
      hyperproliferation to levels similar to a Rag1-/- background. Reconstitution of
      Rag1-/- inducible RAS mice with purified CD8(+) T cells restored microabscess
      formation and epidermal hyperproliferation. Neutralization of IFN-gamma, but not
      of IL-17A, in CD8(+) T-cell-reconstituted Rag1-/- mice expressing RAS blocked CD8
      mediated skin inflammation, inducible nitric oxide synthase expression, and
      keratinocyte hyperproliferation. These results show that CD8(+) T cells can
      orchestrate skin inflammation with psoriasis-like pathology in response to
      constitutive RAS activation in keratinocytes, and this is primarily mediated
      through IFN-gamma.

PMID- 23151853
TI  - Simulation of laser radiation effects on low dimensionality structures.
AB  - This paper presents a study on a system comprised of a low-dimensional structure
      (Ga1-xAlxAs and GaAs quantum well wire), an intense laser field and an applied
      magnetic field in axial direction, resulting in a modified structure by
      interaction with the laser field. A variation of the concentration of aluminum is
      considered. So, the characteristics of the semiconductor such as the effective
      mass and width of the forbidden band vary due to the aluminum concentration. The
      electronic Lande factor control by changing of both intensity and frequency of a
      laser field on cylindrical quantum well wire was also reported. We use the laser
      dressed approximation for the treated "quantum wire + laser" system as quantum
      wire in the absence of radiation but with parameter (electronic barrier height
      and electronic effective mass) renormalized by laser effects. We consider a
      magnetic field applied in the parallel direction of symmetric axis of the quantum
      well wire. We take into account non-parabolicity and anisotropy effects on the
      conduction band by Ogg-McCombe Hamiltonian.

PMID- 23151852
TI  - Molecular dynamics and free energy studies of chirality specificity effects on
      aminobenzo[a]quinolizine inhibitors binding to DPP-IV.
AB  - The aminobenzo[a]quinolizines were investigated as a novel class of DPP-IV
      inhibitors. The stereochemistry of this class plays an important role in the
      bioactivity. In this study, the mechanisms of how different configuration of
      three chiral centers of this class influences the binding affinity were
      investigated by molecular dynamics simulations, free energy decomposition
      analysis. The S configuration for chiral center 3* is decisive for isomers to
      maintain high bioactivity; the chirality effect of chiral center 2* on the
      binding affinity is largely dependent, while the S configuration for chiral
      center 2* is preferable to R configuration for the bioactivity gain; the effect
      of chiral center 11b* on the binding affinity is insignificant. The chirality
      specificity for three chiral centers is responsible for distinction of two van
      der Waals contacts with Tyr547 and Phe357, and of H-bonding interactions with
      Arg125 and Glu206. Particularly, the Arg125 to act as a bridge in the H-bonding
      network contributes to stable H-bonding interactions of isomer in DPP-IV active
      site.

PMID- 23151854
TI  - Usefulness of plasma matrix metalloproteinase-9 level in predicting future
      coronary revascularization in patients after acute myocardial infarction.
AB  - OBJECTIVES: This study aims to determine whether plasma levels of matrix
      metalloproteinases (MMPs) and inflammatory markers can predict the long-term
      prognosis of coronary revascularization in patients after acute myocardial
      infarction (AMI). BACKGROUND: MMPs have been implicated in the development of
      atherosclerosis and plaque rupture in acute coronary syndrome. METHODS: Ninety
      six consecutive patients (63+/-11 years) diagnosed with myocardial infarction
      were enrolled. All patients were followed up for 43+/-12 months. Plasma levels of
      MMP-2 and MMP-9 were determined from blood samples collected immediately after
      hospitalization. Coronary revascularization was defined as having received a
      percutaneous coronary intervention or a coronary artery bypass graft surgery.
      RESULTS: A total of 29 patients (30%) had undergone coronary revascularization
      during the follow-up period, including 27 percutaneous coronary intervention and
      two coronary artery bypass graft surgery. The baseline characteristics were
      similar between groups with or without revascularization. Patients with coronary
      revascularization had significantly higher MMP-9 levels (P=0.048), but not MMP-2
      levels. In addition, a positive correlation was found between circulating MMP-9
      level and total cholesterol (r=0.250, P=0.016) and low-density lipoprotein
      cholesterol (r=0.284, P=0.009). All patients were divided into a high-MMP-9 group
      (highest tertile>=1.10 ng/ml) and a low-MMP-9 group (<1.10 ng/ml). The incidence
      of coronary revascularization was significantly increased in the high-MMP-9 group
      (P=0.034). In a multivariate Cox regression analysis that included MMP-9 and
      classical risk factors, the MMP-9 level was an independent predictor of coronary
      revascularization in patients after AMI (hazard ratio, 2.72; 95% confidence
      interval, 1.24-5.98; P=0.026). CONCLUSION: Increased plasma levels of MMP-9 but
      not MMP-2 or inflammatory markers predict future coronary revascularization, and
      a significant association was observed with MMP-9 and low-density lipoprotein
      cholesterol. These findings suggest a pivotal role of MMP-9 in atherothrombosis
      in AMI patients.

PMID- 23151856
TI  - Is Helicobacter pylori infection associated with Henoch-Schonlein purpura in
      Chinese children? a meta-analysis.
AB  - BACKGROUND: The prevalence of Helicobacter pylori (H. pylori) infection is high
      in China. It not only causes the damage of gastric epithelium, but also plays a
      potential pathogenic role in several extraintestinal diseases. Henoch-Schonlein
      purpura (HSP) is one of the most common vasculitis syndromes affecting children.
      Although its cause is unclear, HSP is often considered to be associated with
      infectious agents. This metaanalysis of previously published studies was
      conducted using a predefined protocol to evaluate the underlying association
      between H. pylori infection and HSP in Chinese children. METHODS: Predefined
      search strategy and inclusion criteria were set up to select studies reporting
      the prevalence of H. pylori infection among HSP children and control groups.
      Included studies were subjected to quality assessment and data extraction by two
      independent reviewers. The pooled odds ratio (OR) was calculated as the effect
      size via both traditional and cumulative meta-analysis. Heterogeneity was
      investigated by subgroup analysis, and the nonparametric "trim and fill" method
      was performed to adjust the overall estimate for the existence of publication
      bias. RESULTS: Ten eligible studies covering 749 HSP children and 560 controls
      were included for metaanalysis. Observational epidemiology studies clearly aimed
      at detecting the potential association between H. pylori infection and HSP with
      retrospective data collection from the children enrolled consecutively. Overall,
      49.27% (369/749) of HSP children had evidence of H. pylori infection compared
      with 23.39% (131/560) of children in the control group. The pooled OR of H.
      pylori infection in HSP children (10 studies with 749 HSP children) was 3.80 [95%
      confidence interval (CI): 2.54-5.68, P<0.001], and the overall estimate from the
      cumulative meta-analysis confirmed the association with more narrow confidence
      interval (OR=3.35, 95% CI: 2.95-3.81). In HSP children mainly with abdominal
      manifestations (8 studies with 337 HSP children), the pooled OR was 4.62 (95% CI:
      2.66-8.01, P<0.001). The adjusted pooled OR was 2.04 (95% CI: 1.48-2.82,
      P<0.001), determined by the nonparametric "trim-andfill" method for eliminating
      the effect of publication bias. H. pylori eradication therapy (4 studies with 266
      HSP children) was capable of reducing the recurrence of HSP (RR=0.38, 95% CI:
      0.25-0.58, P<0.001). Although the subgroup analysis for heterogeneity suggested
      that diagnostic methods and geographical diversity might be account for the
      heterogeneity, statistical analysis of differences revealed no differences
      between subgroups, indicating their limited impact on the overall estimates.
      CONCLUSIONS: These results suggest the necessity of screening H. pylori infection
      in HSP children, particularly in those with gastrointestinal manifestations in
      China. Eradication therapy may reduce the recurrence of HSP in children with H.
      pylori infection. However, further mechanistic and more clinical studies in
      different populations and regions are needed to confirm this association and the
      effect of eradication of H. pylori in HSP children.

PMID- 23151855
TI  - An overview of risk factors for poor neurodevelopmental outcome associated with
      prematurity.
AB  - BACKGROUND: Preterm birth is a major cause of neonatal mortality and morbidity.
      While advances in medical care have improved the survival of preterm infants,
      neurodevelopmental problems persist in this population. This article aims to
      review factors associated with their neurodevelopmental outcomes. DATA SOURCES:
      English language studies of neurodevelopmental outcomes in preterm infants were
      retrieved from PubMed. A total of 100 related publications were included.
      RESULTS: Early gestational age and birth weight are the most significant
      predictors of poor long-term neurological outcome. Structural changes of the
      brain, infection, male gender and neonatal intensive care unit course are also
      important factors affecting eventual outcome. Other complex biological and socio
      economic factors, which extend from prenatal through postnatal periods, up
      through and including adulthood, also affect the trajectory of brain development
      in preterm infants. CONCLUSIONS: Neurodevelopmental problems continue to affect
      the preterm population. There is a critical need for collaboration among
      geneticists, obstetricians, pediatricians, and neuroimaging and rehabilitation
      experts to determine early predictive factors and neuroprotective therapies to
      properly treat or prevent poor neurodevelopmental outcomes in these infants.

PMID- 23151857
TI  - Psychomotor development of children born after preimplantation genetic diagnosis
      and parental stress evaluation.
AB  - BACKGROUND: The increasing number of children conceived following preimplantation
      genetic diagnosis (PGD) necessitates the evaluation of their motor and cognitive
      development. The primary study objective was to evaluate the physical,
      developmental, and neurological outcome of children born after PGD in Greece. In
      addition, the secondary study objective was to compare the stress levels
      regarding parental roles between parents of PGD children and those of naturally
      conceived children. METHODS: A cross-sectional study design was applied. The
      study population consisted of 31 children (aged 2 months to 7.5 years) born after
      PGD analysis and their parents. The developmental evaluation of children included
      a detailed physical evaluation and cognitive assessment with the Bayley Scales of
      Infant Development. The parent stress index was applied to evaluate comparative
      parental stress levels between those parents of PGD children and those of
      naturally conceived healthy children. RESULTS: High rates of caesarean
      deliveries, increased incidence of prematurity, multiples and low-birth weight
      were observed among the 31 PGD children. Overall, 24 of the 31 PGD children had
      cognitive skills within normal range [general developmental quotient (GDQ): 86
      115], while 6 children had lower levels of cognitive skills (GDQ<85). With regard
      to parental stress, PGD parents reported lower levels of parenting stress as
      compared to parents of naturally conceived children (P<0.01). CONCLUSIONS: The
      enhanced frequency of poor cognitive and motor skills as well as low parental
      stress necessitates early detection and intervention for developmental delays
      among PGD children.

PMID- 23151858
TI  - Sensitization to food allergens in Iranian children with mild to moderate
      persistent asthma.
AB  - BACKGROUND: Asthma is the most common chronic respiratory disease in childhood.
      The clinical presentation of asthma may worsen after food allergen ingestion in
      sensitized patients. To avoid nonspecific dietary restrictions in children with
      asthma, laboratory-based advice about foods is potentially helpful. The purpose
      of this study was to determine food sensitization in children with asthma.
      METHODS: Seventy-nine children with mild to moderate persistent asthma were
      included in this study. Commercial food allergens including cow's milk, egg
      white, almond, potato, and soybean were used in skin prick tests. Specific IgE to
      20 common food allergens was also measured in serum. RESULTS: Twelve (15.2%) of
      the patients had a positive skin prick test to at least one of the five food
      extracts. Sensitization was detected by skin prick tests to cow's milk and egg
      white (each 6.3%), almond (3.8%), potato (2.5%) and soybean (1.3%). Specific IgE
      levels >=0.35 kAU/L were detected in the serum of 47% of the children with
      asthma. The most common food allergens were cow's milk (26.6%), hazelnuts
      (25.3%), wheat flour (15.2%) and egg white (12.6%). Patients with a history of at
      least one hospital admission due to asthma attack had a higher rate of
      sensitization to egg. CONCLUSIONS: In our study, food sensitization was frequent
      in Iranian children with asthma. Although clinical food allergy could not be
      evaluated because food challenge tests were not used in our study, skin prick
      tests and serum-specific IgE to common food allergens might be helpful in
      identifying children with food sensitization.

PMID- 23151860
TI  - +276 G/T single nucleotide polymorphism of the adiponectin gene is associated
      with the susceptibility to biliary atresia.
AB  - BACKGROUND: Biliary atresia (BA) is an intractable neonatal inflammatory and
      obliterative cholangiopathy, leading to progressive fibrosis and cirrhosis.
      Adiponectin, an anti-inflammatory adipokine, is known to play a possible role in
      liver diseases. The objective of our study was to determine the relationship
      between adiponectin gene polymorphisms and BA susceptibility. METHODS: A total of
      106 BA patients and 107 healthy controls were included in this study. Two single
      nucleotide polymorphisms (SNPs) of the adiponectin gene, +45T/G (rs2241766) and
      +276G/T (rs1501299), were genotyped by polymerase chain reaction-restriction
      fragment length polymorphism analysis. RESULTS: Genotype distributions of +45 T/G
      and +276 G/T SNPs were seen in the Hardy-Weinberg equilibrium for both BA
      patients and controls. The frequency of the G/G genotype at +276G/T was
      significantly higher in BA patients than in the controls (P=0.009). Regarding
      +45T/ G in BA patients, the frequency of the T/T genotype tended to be lower than
      in the controls, but the difference was not significant. Moreover, the G allele
      at +276G/T in BA patients was more common than in the controls (P=0.0043). In
      contrast, the frequency of the T allele at +45T/G was not significantly different
      between BA patients and the controls. None of the haplotypes studied was found to
      significantly influence the risk of BA. CONCLUSIONS: +276G/T SNP is strongly
      associated with BA, particularly with the G allele. We postulate that the +276G/T
      adiponectin gene polymorphism confers increased susceptibility to BA.

PMID- 23151859
TI  - Clinical and epidemiological characteristics of 2009 pandemic influenza A in
      hospitalized pediatric patients of the Saurashtra region, India.
AB  - BACKGROUND: The first case of 2009 pandemic influenza A or H1N1 virus infection
      in India was reported in May 2009 and in the Saurashtra region in August 2009. We
      describe the two waves clinicoepidemiological characteristics of children who
      were hospitalized with 2009 influenza A infection in the Saurashtra region.
      METHODS: From September 2009 to February 2011, we treated 117 children infected
      with 2009 influenza A virus who were admitted in different hospitals in Rajkot
      city. Real-time reverse transcriptase polymerase chain reaction (RT-PCR) test was
      used to confirm infection, and the clinico-epidemiological features of the
      disease were closely monitored. RESULTS: In the 117 patients, with a median age
      of 2 years, 59.8% were male. The median time from onset of the disease to
      influenza A diagnosis was 5 days, and that from onset of the disease to
      hospitalization was 7 days. The admitted patients took oseltamivir, but only
      11.1% of them took it within 2 days after onset of the disease. More than one
      fourth (29.1%) of the admitted patients died. The most common symptoms of the
      patients were cough (98.3%), fever (94.0%), sore throat and shortness of
      breathing. Pneumonia was detected by chest radiography in 80.2% of the patients.
      CONCLUSIONS: In children with infection-related illness, the survival rate was
      about 71% after oseltamivir treatment. The median time for virus detection with
      real-time RT-PCR is 5 days. Early diagnosis and treatment may reduce the severity
      of the disease.

PMID- 23151861
TI  - Decrease of renal aquaporins 1-4 is associated with renal function impairment in
      pediatric congenital hydronephrosis.
AB  - BACKGROUND: Renal aquaporins (AQP1-4) concentration is downregulated and is in
      proportion to the degree of hydronephrosis graded by ultrasound in pediatric
      congenital hydronephrosis (CH). However, the relationship between the expression
      of AQP1-4 with the changes of renal function impairment (RFI) evaluated by
      (99m)Tc-DTPA renal dynamic imaging is still unclear. This study aimed to
      investigate the relationship between AQP1-4 expression and degree of RFI in
      children with CH. METHODS: The expression of AQP1-4 was evaluated in 45 children
      with unilateral ureteropelvic junction obstruction (28 boys and 17 girls, average
      age: 28+/-10 months) and 15 children undergoing nephrectomy for nephroblastoma (8
      boys and 7 girls, average age: 26+/-8 months) by immunoblotting and
      immunohistochemistry. Renal function was graded into mild and severe RFI by
      (99m)Tc-DTPA renal dynamic imaging. RESULTS: One-way analysis of variance with
      Bonferonni's correction showed a significantly reduced protein expression of AQP1
      4 in the severe RFI group compared with those in both mild RFI group and controls
      (AQP1: 0.52+/-0.09 vs. 0.91+/-0.06 vs. 1.23+/-0.033; AQP2: 0.68+/-0.12 vs. 1.09+/
      0.06 vs. 1.52+/-0.08; AQP3: 0.59+/-0.16 vs. 0.94+/-0.08 vs. 1.31+/-0.07; AQP4:
      0.64+/-0.06 vs. 1.14+/-0.07 vs. 1.61+/-0.07; P<0.001, respectively). In kidneys
      with severe RFI, there was a reduction in the protein concentration of all four
      AQP isoforms which was more pronounced compared with those seen in kidneys with
      mild RFI and in the controls. CONCLUSION: AQP1-4 expression is reduced in
      proportion with the impairment degree of renal function graded by (99m)Tc-DTPA
      renal dynamic imaging in human CH.

PMID- 23151862
TI  - Diffusion-weighted MRI for detection and differentiation of musculoskeletal
      tumorous and tumor-like lesions in pediatric patients.
AB  - BACKGROUND: MRI is the diagnostic mainstay for detection and differentiation of
      musculoskeletal tumors. However, a projection regarding the biological dignity of
      lesions based on standard MRI sequences remains difficult and uncertain. This
      study was undertaken to analyse whether diffusion-weighted MRI (DWI) can
      distinguish between benign and malignant musculoskeletal tumorous and tumor-like
      lesions in pediatric patients. METHODS: MR examinations of 44 consecutive
      pediatric patients (26 girls, mean age 11+/-6 years) including standard sequences
      and DWI (b=50/800 s/mm(2)) at 1.5 or 3 Tesla were retrospectively evaluated. The
      study group contained 10 patients with non-treated malignant tumors and 34
      patients with benign lesions. Size, relative signal intensity and apparent
      diffusion coefficient (ADC, unit *10(-3) mm(2)/s) were determined in one lesion
      per patient. RESULTS: Mean ADC was 0.78+/-0.45*10(-3) mm(2)/s in patients with
      malignant tumors and 1.71+/-0.75 *10(-3) mm(2)/s in patients with benign lesions
      (P<0.001). Relative operating characteristics (ROC) analysis showed a sensitivity
      of 90% and a specificity of 91% for malignancy, based on an ADC cut-off value of
      <=1.03. On logistic regression, mean ADC and lesion size accounted for 62% of
      variability in benign vs. malignant tumors. For malignant tumors, the signal
      intensity ratio was higher on DWI than on T1w post-contrast images (P<0.002). Two
      cases of local tumor recurrence were diagnosed by DWI only. CONCLUSIONS: DWI
      shows promising results for determination of biological dignity in
      musculoskeletal tumors. Mean ADC <=1.03*10(-3) mm(2)/s is a strong indicator of
      malignancy at the first diagnosis. The use of DWI for early diagnosis of tumor
      recurrence in comparison with standard MRI sequences should be evaluated in
      prospective studies.

PMID- 23151863
TI  - Mid-term differences in right ventricular function in patients with congenital
      diaphragmatic hernia compared with controls.
AB  - BACKGROUND: Patients with congenital diaphragmatic hernia (CDH) may have abnormal
      lung development, which may cause detrimental effects on right ventricular (RV)
      function. This study aimed to determine if there are persistent echocardiographic
      differences in RV function in patients with CDH years after repair versus control
      patients. METHODS: Patients who underwent repair for CDH were recruited. RV
      function was evaluated by strain analysis and tissue Doppler imaging (TDI).
      Wilcoxon's rank-sum test was used for analysis. RESULTS: Seven CDH patients and
      16 control patients were studied. There was no difference in age between the CDH
      and control groups (6.2+/-1.7 years vs. 5.7+/-1.7 years). TDI demonstrated
      significantly lower values in the RV early diastolic wave (12.8+/-1.5 cm/s vs.
      16.1+/-3.1 cm/s) and RV systolic wave (10.2+/- 0.8cm/s vs. 13.4+/-1.3 cm/s) when
      comparing the CDH group and the control group. Interventricular apical septal
      strain was signifi cantly lower in the CDH group than in the control group (
      20.1+/-4.6% vs. -25.4+/-4.1%). There was a trend towards lower strain values in
      the RV mid-lateral segment in the CDH group (-30.8+/-9.9% versus -39.7+/-6.0%,
      P=0.06) and a lower global RV strain (-27.8+/-3.0% vs. -31.1+/-3.1%, P=0.06).
      CONCLUSIONS: Patients who underwent CDH repair continue to have differences in RV
      function years after repair. Follow-up is needed to determine how these
      differences impact cardiac function in adult survivors of CDH.

PMID- 23151864
TI  - A comparison of criteria for diagnosis of atopic dermatitis in children.
AB  - BACKGROUND: Atopic dermatitis (AD) diagnosis in children gives rise to many
      problems. Although the Hanifin and Rajka criteria are acknowledged and used
      universally in diagnosing AD, their evaluation is a major source of difficulty in
      pediatrician's daily practice. The simplified criteria, revised by Williams et
      al, seem to be more useful and represent the most common clinical manifestations
      of AD. The aim of the present study was to compare the efficacy of the two
      different criteria for diagnosing AD in children. METHODS: This study involved
      250 children with AD. All of the patients underwent clinical examinations and the
      diagnostic procedures according to the criteria of Hanifin and Rajka as well as
      those of Williams. RESULTS: According to the Hanifin-Rajka criteria, AD was
      diagnosed in 173 children, of whom 153 were diagnosed positive by the criteria of
      Williams. Among the 77 children who were diagnosed without AD according to the
      Hanifin and Rajka criteria, 4 were detected with AD by the Williams criteria.
      Four children with scabies and seborrhoeic dermatitis were misdiagnosed as having
      AD according to the Williams criteria due to the atypical locations of their
      lesions and the histories of asthma or hay fever and xerosis. CONCLUSIONS:
      Although the criteria of Hanifin and Rajka are the gold standard for diagnosing
      AD, the Williams criteria are also very useful in children older than 4 years.
      The most useful Williams criteria for AD diagnosis in children is pruritus with
      history of lesions in characteristic locations and history of generally dry skin.
      The significant increase in the detectability of AD is found by raising the
      borderline age for the first skin lesion development from 2 to 5 years of age.

PMID- 23151865
TI  - Beta-galactosidase deficiencies and novel GLB1 mutations in three Chinese
      patients with Morquio B disease or GM1 gangliosidosis.
AB  - BACKGROUND: This paper aims to report GLB1 activities and mutation analysis of
      three patients from the mainland of China, one with Morquio B disease and two
      with GM1 gangliosidosis. METHODS: GLB1 activity and GLB1 gene mutation were
      analyzed in the three patients who were clinically suspected of having Morquio B
      disease or GM1 gangliosidosis. Novel mutations were analyzed by aligning GLB1
      homologs, 100 control chromosomes, and the PolyPhen-2 tool. RESULTS: The
      enzymatic activity of GLB1 was found to be 5.03, 4.20, and 4.50 nmol/h/mg in the
      three patients, respectively. Patient 1 was a compound heterozygote for
      p.[Arg148Cys] and p.[Tyr485Cys] mutations in the GLB1 gene. Patient 2 was a
      compound heterozygote for p.[Tyr270Phe] and p.[Leu337Pro] mutations. Patient 3
      was a homozygote for p.[Asp448Val] mutation. Three mutations (p.[Tyr485Cys],
      p.[Tyr270Phe] and p.[Leu337Pro]) were novel variants and were predicted to damage
      GLB1 function. CONCLUSIONS: The enzymatic activity and related gene analysis of
      beta-galactosidase should be performed in clinically suspected individuals to
      confirm diagnosis. The three novel mutations, p.[Tyr485Cys], p.[Tyr270Phe], and
      p.[Leu337Pro], are thought to be disease-causing mutations.

PMID- 23151866
TI  - Tick-borne encephalitis in children and adolescents in the Czech Republic between
      1960 and 2007.
AB  - BACKGROUND: The Czech Republic ranks among the countries with the highest
      prevalence of tick-borne encephalitis worldwide. The region of West Bohemia has
      the second highest morbidity within the Czech Republic. METHODS: Between 1960 and
      2007, laboratories confirmed 410 cases of tick-borne encephalitis in children and
      adolescents of West Bohemia. Available epidemiological data were analyzed.
      RESULTS: The highest incidence (per 100 000 population) was found in the group of
      15-19 years for both genders (males: 6.2; females: 4.3). Data on the consumption
      of non-pasteurized milk were found in 5.4% of patients. The preschool age group
      showed its highest incidence in June and September, and the risk of infection for
      older children was in July and August. CONCLUSIONS: The current low coverage of
      vaccination leads to an insignificant improvement to the overall frequency of
      this disease.

PMID- 23151867
TI  - Peritoneal metastasis of third ventricular atypical teratoid/rhabdoid tumor after
      VP shunt implantation for unexplained hydrocephalus.
AB  - BACKGROUND: Atypical teratoid/rhabdoid tumor (AT/RT) of the central nervous
      system (CNS) is a highly malignant neoplasm seen frequently in infancy and early
      childhood. This report presents a 9-year-old girl of primary third ventricular
      AT/RT with peritoneal metastasis after ventriculoperitoneal (VP) shunt catheter
      implantation for hydrocephalus before the identification of the CNS tumor.
      METHODS: The data of clinical course, laboratory and imaging studies were
      obtained and carefully reviewed. Serial imaging studies including enhanced CT and
      MRI were performed at the first admission, during which the patient was diagnosed
      with a non-malignant communicating hydrocephalus. Secondary radiological studies
      were carried out 5 months after VP shunt, during which the patient demonstrated
      worsening clinical signs of intracranial hypertension. An imaging study
      identified a tumor in the third ventricle. RESULTS: The patient was treated by a
      surgical resection, showing the specimen was pathologically consistent with AT/RT
      5 months after VP shunt. Systematic chemotherapy and radiotherapy were prescribed
      for the patient. After 6 months, PET/CT revealed peritoneal metastasis but
      negative findings in the CNS. The parents of the patient refused further
      intervention, and she died one month later. CONCLUSION: VP shunt in a patient
      with AT/RT may cause distant seeding of the tumor in unrelated areas of the body,
      even after intensive multimodality treatment. Further studies on shunt related
      metastases are needed.

PMID- 23151868
TI  - Successful surgical repair of d-transposition of the great arteries in a
      separated conjoined twin.
AB  - Conjoined twins are very rare examples of congenital malformations. In 75% of
      thoracoomphalopagus conjoined twins, the intracardiac anatomy determines outcome
      and long-term survival. METHODS: We successfully separated one case of thoraco
      omphalopagus conjoined twins, with one having d-transposition of the great
      arteries. After control of sepsis, the twin underwent an arterial switch and
      complete repair of her cardiac defect. RESULTS: She made a full recovery and was
      discharged from the hospital 20 days after surgery. CONCLUSION: Careful planning,
      skillful surgical separation and cardiac surgery by a combined medical and
      surgical team is the key to save the twins in such a rare case.

PMID- 23151869
TI  - Reference measurement procedures for the iron saturation in human transferrin
      based on IDMS and Raman scattering.
AB  - Two reference measurement procedures are presented here that allow the
      determination of the iron saturation in human transferrin, based on different
      molecular properties. The results, directly derived from the number of ions bound
      to the protein molecule, are traceable to the SI. Up to now, the iron saturation
      has only been deduced indirectly from the amount-of-substance ratio of serum iron
      to transferrin in serum. Interlaboratory tests have shown the need for more
      accurate methods, as the results from many participant test samples for both
      parameters do not lie within the acceptable range of deviation given by relevant
      guidelines when different methods or kits are applied. Using isotope dilution, an
      HPLC ICP-MS procedure was developed in compliance with the requirements of a
      primary reference measurement procedure. In this manner, the iron saturation was
      measured with an associated relative expanded measurement uncertainty of 4%.
      Based on the results, a straightforward Raman procedure was evolved, which allows
      the determination of the iron saturation in transferrin with an associated
      relative expanded uncertainty of 7%.

PMID- 23151870
TI  - Experimental epidural hematoma causes cerebral infarction and activates
      neocortical glial and neuronal genesis in adult guinea pigs.
AB  - Epidural hematoma (EDH) is a type of life-threatening traumatic brain injury.
      Little is known about the extent to which EDH may cause neural damage and
      regenerative response in the cerebral cortex. Here we attempted to explore these
      issues by using guinea pigs as an experimental model. Unilateral EDH was induced
      by injection of 0.1 ml autologous blood into the extradural space, with
      experimental effects examined at 7, 14, 30, and 60 days postlesion. An infarct
      developed in the cortex deep to the EDH largely after 7 days postlesion, with
      neuronal death occurred from layers I to V in the central infarct region, as
      evidenced by loss of immunoreactivity (IR) for neuron-specific nuclear antigen
      (NeuN). Glial fibrillary acidic protein (GFAP) IR appeared as a cellular band
      surrounding the infarct and extending into the periinfarct cortex along the pia.
      Doublecortin (DCX) IR emerged in these same areas, with labeled cells appearing
      as astrocytic and neuronal profiles. DCX/GFAP colocalization was found in these
      regions commonly at 7 and 14 days postlesion, whereas DCX/NeuN-colabeled neurons
      were detectable at 30 and 60 days postlesion. Subpopulations of GFAP-, DCX-, or
      NeuN-immunoreactive cells colocalized with the endogenous proliferative marker Ki
      67 or bromodeoxyuridine (BrdU) after pulse-chase with this birth-dating marker.
      The results suggest that experimental EDH can cause severe neuronal loss, induce
      significant glial activation, and promote a certain degree of local neuronal
      genesis in adult guinea pig neocortex. These findings point to potential
      therapeutic targets for improving neuronal recovery in clinical management of
      EDH.

PMID- 23151871
TI  - Identification of TCT, a novel knockdown resistance allele mutation and analysis
      of resistance detection methods in the voltage-gated Na+ channel of Culex pipiens
      pallens from Shandong Province, China.
AB  - The present study aimed to investigate deltamethrin resistance in Culex pipiens
      pallens (C. pipiens pallens) mosquitoes and its correlation with knockdown
      resistance (kdr) mutations. In addition, mosquito-resistance testing methods were
      analyzed. Using specific primers in polymerase chain reaction (PCR) and allele
      specific (AS)-PCR, kdr gene sequences isolated from wild C. pipiens pallens
      mosquitoes were sequenced. Linear regression analysis was used to determine the
      correlation between the mutations and deltamethrin resistance. A kdr allelic gene
      was cloned and sequenced. Analysis of the DNA sequences revealed the presence of
      two point mutations at the L1014 residue in the IIS6 transmembrane segment of the
      voltage-gated sodium channel (VGSC): L1014F, TTA->TTT, replacing a leucine (L)
      with a phenylalanine (F); L1014S, TTA->TCA, replacing leucine (L) with serine
      (S). Two alternative kdr-like mutations, L1014F and L1014S, were identified to be
      positively correlated with the deltamethrin-resistant phenotype. In addition a
      novel mutation, TCT, was identified in the VGSC of C. pipiens pallens. PCR and AS
      PCR yielded consistent results with respect to mosquito resistance. However, the
      detection rate of PCR was higher than that of AS-PCR. Further studies are
      required to determine the specific resistance mechanism. PCR and AS-PCR
      demonstrated suitability for mosquito resistance field tests, however, the former
      method may be superior to the latter.

PMID- 23151872
TI  - Biomechanical analysis of corrective forces in spinal instrumentation for
      scoliosis treatment.
AB  - STUDY DESIGN: Computer modeling and simulations to analyze correction forces at
      the bone-screw interface in scoliosis instrumentation. OBJECTIVE: To derive the
      minimum corrective forces applied on vertebrae through pedicle screws to achieve
      desired scoliosis corrections and evaluate the actual bone-screw forces
      associated with 3 types of pedicle screws (monoaxial, polyaxial, and dorsoaxial).
      SUMMARY OF BACKGROUND DATA: The optimum screw pattern has not been established in
      the literature. The final bone-screw forces in scoliosis instrumentation consist
      of "true corrective forces" (i.e., the minimum forces required to achieve the
      desired corrections without considering adequate rod seating at all pedicle
      screws) and "extra forces" (EF) (i.e., supplementary forces applied to ensure
      proper rod seating when the attachment of some screws is not in compliance with
      the attachment of their neighboring screws; they have no benefit to overall
      corrections). METHODS.: Using patient-specific computer models, true corrective
      forces were estimated for 10 spinal instrumentation cases. EF were computed by
      simulating the instrumentations of the 10 cases using respectively monoaxial,
      polyaxial, and dorsoaxial screws. RESULTS: The average true corrective forces
      were 50 +/- 30 N. The average bone-screw forces were 229 +/- 140 N, 141 +/- 99 N,
      and 103 +/- 42 N, respectively, for monoaxial, polyaxial, and dorsoaxial screws;
      the averages of the EF magnitudes were 205 +/- 136 N, 125 +/- 93 N, and 65 +/- 39
      N, respectively. CONCLUSION: Bone-screw forces to achieve desired corrections can
      be minimized. However, EF are inevitable to secure the locking of all screws.
      Higher EF were associated with pedicle screws, with less degrees of freedom for
      connecting screw body to rod, that is, monoaxial followed by polyaxial and then
      by dorsoaxial screws.

PMID- 23151873
TI  - Use of the video telescope operating monitor (VITOM) as an alternative to the
      operating microscope in spine surgery.
AB  - STUDY DESIGN: Prospective cohort study. OBJECTIVE: To evaluate the efficacy of
      video telescope operating monitor (VITOM) as an alternative to operative
      microscope (OM) in spinal surgery. SUMMARY OF BACKGROUND DATA: The surgical
      operating microscope can be expensive, cumbersome, and ergonomically
      disadvantageous. VITOM is a novel telescope-based exoscope system that can be
      used as an alternative or supplement to OM. METHODS: Patients undergoing spinal
      surgery were enrolled in a prospective cohort study between December 2008 and
      March 2011. Age, sex, and operation-matched patients undergoing surgery using the
      standard OM served as the control group. During surgery, the VITOM system was
      used in place of the OM in 24 patients. Operative time, length of postoperative
      hospital stay, and intraoperative complications were assessed. RESULTS.: A total
      of 48 patients were studied in 2 equal cohorts of 24 patients each. Within each
      cohort, patients underwent single-level (n = 4) and 2-level (n = 7) posterior
      decompression as well as single-level (n = 11) and 2-level (n = 2) transforaminal
      lumbar interbody fusions via VITOM, with an equal number of controls using OM.
      There were no significant differences in age (P = 0.79) or sex (P = 0.77) between
      cohorts.There were no statistically significant differences in mean operative
      room time for single-level decompressions (P = 0.38), 2-level decompressions (P =
      0.12), single-level transforaminal lumbar interbody fusions (P = 0.13), or 2
      level transforaminal lumbar interbody fusions (P = 0.15). Postoperative hospital
      length of stay averaged 2.9 days for the VITOM group versus 2.8 days for the
      traditional OM group (P = 0.75). There were no intraoperative complications in
      either group. Subjectively, surgeons rated the image quality as very high and
      equal to the OM. CONCLUSION: The VITOM system for spinal surgery provides
      outstanding image quality and an ease of manipulation rivaling the OM. There were
      no statistically significant differences in mean operative room time,
      intraoperative complications, or total hospital length of stay when using this
      novel system in several common spinal procedures relative to the OM.

PMID- 23151874
TI  - Paraspinal chordoma mimicking a neurofibroma: a rare but important radiological
      pitfall.
AB  - We present an unusual case of a chordoma presenting as an extradural spinal
      tumour with extension through an expanded intervertebral foramen to form a large
      paraspinal mass. The magnetic resonance imaging appearances closely mimicked a
      neurofibroma; however, pre-operative biopsy confirmed the diagnosis of chordoma.
      This is, to our knowledge, the tenth reported case of chordoma presenting as a
      mass expanding the intervertebral foramen. Thus, while it is a rare form of
      chordoma, it can lead to a recognised radiological pitfall. Making the
      distinction from neurofibroma before surgery is essential, as radical dissection
      of chordoma is required to reduce the risk of local recurrence.

PMID- 23151875
TI  - Injecting epidural and intra-articular triamcinolone in HIV-positive patients on
      ritonavir: beware of iatrogenic Cushing's syndrome.
AB  - We report two HIV-positive patients on highly active antiretroviral therapy
      (HAART) who developed clinical features in keeping with secondary adrenal
      suppression following epidural and subacromial triamcinolone. Both patients were
      on ritonavir-boosted protease inhibitor containing HAART and both required
      maintenance hydrocortisone therapy following diagnosis. This highlights the need
      for radiologists and clinicians practicing these injections to be aware of this
      complication, to elicit an accurate drug history, and to take adequate measures
      to minimize these adverse effects.

PMID- 23151876
TI  - Magnetic resonance imaging for extramammary Paget's disease: radiological and
      pathological correlations.
AB  - Extramammary Paget's disease (EMPD) is a rare cutaneous neoplasm that is thought
      to represent intraepithelial adenocarcinoma developing in an area rich in
      apocrine glands. Magnetic resonance imaging (MRI) findings for this disease are
      not well established. We report three cases of pathologically confirmed EMPD in
      which MRI was performed before surgery. The lesions were widespread in the
      epidermis and the dermis. Lesions were sharply well enhanced on gadolinium
      enhanced T1-weighted imaging and appeared hyperintense on diffusion-weighted
      imaging in all cases. Areas with enhancement in depth corresponded well with the
      pathological lesion. In addition, different malignant legions were found on the
      same images from MRI in two cases, indicating potential associations with other
      malignancies. We describe the MRI findings and their pathological correlation.
      MRI could be useful for preoperative evaluation of disease spread and detection
      of associated malignancies.

PMID- 23151877
TI  - Cannabinoid receptor agonists upregulate and enhance serotonin 2A (5-HT(2A))
      receptor activity via ERK1/2 signaling.
AB  - Recent behavioral studies suggest that nonselective agonists of cannabinoid
      receptors may regulate serotonin 2A (5-HT(2A)) receptor neurotransmission. Two
      cannabinoids receptors are found in brain, CB1 and CB2 receptors, but the
      molecular mechanism by which cannabinoid receptors would regulate 5-HT(2A)
      receptor neurotransmission remains unknown. Interestingly, we have recently found
      that certain cannabinoid receptor agonists can specifically upregulate 5-HT(2A)
      receptors. Here, we present experimental evidence that rats treated with a
      nonselective cannabinoid receptor agonist (CP 55,940, 50 ug/kg, 7 days) showed
      increases in 5-HT(2A) receptor protein levels, 5-HT(2A) receptor mRNA levels, and
      5-HT(2A) receptor-mediated phospholipase C beta (PLCbeta) activity in prefrontal
      cortex (PFCx). Similar effects were found in neuronal cultured cells treated with
      CP 55,940 but these effects were prevented by selective CB2, but not selective
      CB1, receptor antagonists. CB2 receptors couple to the extracellular kinase (ERK)
      signaling pathway by Galpha(i/o) class of G-proteins. Noteworthy, GP 1a
      (selective CB2 receptor agonist) produced a strong upregulation of 5-HT(2A)
      receptor mRNA and protein, an effect that was prevented by selective CB2 receptor
      antagonists and by an ERK1/2 inhibitor, PD 198306. In summary, our results
      identified a strong cannabinoid-induced upregulation of 5-HT(2A) receptor
      signaling in rat PFCx. Our cultured cell studies suggest that selective CB2
      receptor agonists upregulate 5-HT(2A) receptor signaling by activation of the
      ERK1/2 signaling pathway. Activity of cortical 5-HT(2A) receptors has been
      associated with several physiological functions and neuropsychiatric disorders
      such as stress response, anxiety and depression, and schizophrenia. Therefore,
      these results may provide a molecular mechanism by which activation of
      cannabinoid receptors might be relevant to the pathophysiology of some cognitive
      and mood disorders in humans.

PMID- 23151878
TI  - Cleavage and polyadenylation specificity factor 1 (CPSF1) regulates alternative
      splicing of interleukin 7 receptor (IL7R) exon 6.
AB  - Interleukin 7 receptor, IL7R, is expressed exclusively on cells of the lymphoid
      lineage, and its expression is crucial for the development and maintenance of T
      cells. Alternative splicing of IL7R exon 6 results in membrane-bound (exon 6
      included) and soluble (exon 6 skipped) IL7R isoforms. Interestingly, the
      inclusion of exon 6 is affected by a single-nucleotide polymorphism associated
      with the risk of developing multiple sclerosis. Given the potential association
      of exon 6 inclusion with multiple sclerosis, we investigated the cis-acting
      elements and trans-acting factors that regulate exon 6 splicing. We identified
      multiple exonic and intronic cis-acting elements that impact inclusion of exon 6.
      Moreover, we utilized RNA affinity chromatography followed by mass spectrometry
      to identify trans-acting protein factors that bind exon 6 and regulate its
      splicing. These experiments identified cleavage and polyadenylation specificity
      factor 1 (CPSF1) among protein-binding candidates. A consensus polyadenylation
      signal AAUAAA is present in intron 6 of IL7R directly downstream from the 5'
      splice site. Mutations to this site and CPSF1 knockdown both resulted in an
      increase in exon 6 inclusion. We found no evidence that this site is used to
      produce cleaved and polyadenylated mRNAs, suggesting that CPSF1 interaction with
      intronic IL7R pre-mRNA interferes with spliceosome binding to the exon 6 5'
      splice site. Our results suggest that competing mRNA splicing and polyadenylation
      regulate exon 6 inclusion and consequently determine the ratios of soluble to
      membrane-bound IL7R. This may be relevant for both T cell ontogeny and function
      and development of multiple sclerosis.

PMID- 23151880
TI  - Novel Y chromosome breakpoint in an infertile male with a de novo translocation
      t(Y;16): a case report.

PMID- 23151881
TI  - Arterial pressure in animal models of fetal programming:  hypertensive or
      hyperresponsive?

PMID- 23151879
TI  - In vitro culture and morphological characterization of prepubertal buffalo
      (Bubalus bubalis) putative spermatogonial stem cell.
AB  - PURPOSE: Spermatogonial stem cells (SSCs) have the unique ability both to self
      renew and to produce progeny that undergo differentiation to spermatozoa. The
      present study has been carried out to develop a method to purify and enrich the
      pure populations of spermatogonial stem cell like cells in buffalo. METHODS: The
      spermatogonial cells were isolated from testes of 3-7 month old buffalo calves
      and disaggregated by double enzymatic digestion. Mixed population of isolated
      cells were then plated on Datura stramonium agglutinin (DSA) lectin coated dishes
      for attachment of Sertoli cells. The desired cells were obtained from suspension
      medium after 18 h of incubation and then loaded on discontinuous density gradient
      using percoll (20-65 %) and different types of spermatogonia cells were obtained
      at interface of each layer. These cells were cultured in vitro. RESULTS:
      Spermatogonial cells isolated have spherical outline and two or three
      eccentrically placed nucleoli, created a colony after proliferation during first
      week or immediately after passage. After 7-10 days of culture, the resulted
      developed colonies of spermatogonial cells expressed the spermatogonial specific
      genes like Plzf and VASA; and other pluripotency related markers viz. alkaline
      phosphtase, DBA, CD9, CD90, SSEA-1, OCT-4, NANOG and REX-1. CONCLUSION: Our
      results show that the isolated putative spermatogonial stem cells exhibit the
      expression of pluripotency related and spermatogonial specific genes. This study
      may help to establish a long term culture system for buffalo spermatogonia.

PMID- 23151882
TI  - Obesity paradox or inappropriate study designs? Time for life-course
      epidemiology.

PMID- 23151883
TI  - Augmentation index as a specific marker of large arteries distensibility:  the
      end of a beautiful tale?

PMID- 23151884
TI  - Echocardiographic left ventricular hypertrophy:  implications for clinicians.

PMID- 23151885
TI  - Hypertension:  an immunologic disease?

PMID- 23151886
TI  - Comment on ESH position paper: renal denervation--an interventional therapy of
      resistant hypertension.

PMID- 23151888
TI  - [Practical diagnostics of acid-base disorders: part I: differentiation between
      respiratory and metabolic disturbances].
AB  - The first part of this overview on diagnostic tools for acid-base disorders
      focuses on basic knowledge for distinguishing between respiratory and metabolic
      causes of a particular disturbance. Rather than taking sides in the great
      transatlantic or traditional-modern debate on the best theoretical model for
      understanding acid-base physiology, this article tries to extract what is most
      relevant for everyday clinical practice from the three schools involved in these
      keen debates: the Copenhagen, the Boston and the Stewart schools. Each school is
      particularly strong in a specific diagnostic or therapeutic field. Appreciating
      these various strengths a unifying, simplified algorithm together with an acid
      base calculator will be discussed.

PMID- 23151889
TI  - Surfactin suppresses TPA-induced breast cancer cell invasion through the
      inhibition of MMP-9 expression.
AB  - Metastasis is the main cause of cancer mortality. In this study, we investigated
      the effects of surfactin, a cyclic lipopeptide produced by Bacillus subtilis, on
      cancer metastasis in vitro and the underlying molecular mechanisms involved.
      Surfactin inhibited the 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced
      invasion, migration and colony formation of human breast carcinoma cells. Western
      blot analysis, gelatin zymography and reverse transcription-PCR analysis revealed
      that matrix metalloproteinase-9 (MMP-9) expression and activation was
      significantly suppressed by surfactin in a dose-dependent manner. Surfactin
      attenuated TPA-induced nuclear translocation and activation of nuclear factor
      kappaB (NF-kappaB) and activator protein-1 (AP-1). Furthermore, surfactin
      strongly repressed the TPA-induced phosphorylation of Akt and extracellular
      signal-regulated kinase (ERK). Treatment with specific inhibitors of Akt and ERK
      suppressed MMP-9 expression and activation. These results suggest that the
      surfactin-mediated inhibition of breast cancer cell invasion and MMP-9 expression
      involves the suppression of the NF-kappaB, AP-1, phosphatidylinositol 3-kinase
      (PI-3K)/Akt and the ERK signaling pathways. Thus surfactin may have potential
      value in therapeutic strategies for the treatment of breast cancer metastasis.

PMID- 23151891
TI  - Response to Independent association between obstructive sleep apnea and
      noncalcified coronary plaque demonstrated by noninvasive coronary computed
      tomography angiography.

PMID- 23151890
TI  - Is there any predictor for tinnitus outcome in different types of otologic
      surgery?
AB  - Our objective was to determine the effect of different types of otologic
      surgeries on tinnitus symptoms. Our study consisted of 63 patients who were
      operated between January and June 2011. Variables such as age, sex, presence of
      systemic diseases, location and size of the perforation, duration of dry period,
      type of otological surgery, peroperative presence of cholesteatoma,
      timpanosclerotic plaques and ossicular chain discontinuity were evaluated.
      Audiologic evaluation by pure tone audiometry and assessment of THI scores were
      conducted before surgery and 12 weeks after surgery. There was a very significant
      difference between preoperative and postoperative mean THI scores (p < 0.01).
      There was no significant effect of presence of ossicular discontinuity,
      cholesteatoma, tympanosclerotic plaques, type of surgery or duration of symptoms
      on the difference of preoperative and postoperative THI scores (p > 0.05). There
      was a significant positive relationship between audiological gain and THI scores
      (r = 0.355, p < 0.01). In our study, we investigated the relationship between
      many types of otological surgeries including some preoperative and peroperative
      pathological findings and tinnitus. As a result, we found that postoperative
      audiologic gain is an important factor determining outcome of tinnitus in these
      types of otological surgeries.

PMID- 23151892
TI  - Super-resolution track-density imaging of thalamic substructures: comparison with
      high-resolution anatomical magnetic resonance imaging at 7.0T.
AB  - The thalamus is one of the most important brain structures, with strong
      connections between subcortical and cortical areas of the brain. Most of the
      incoming information to the cortex passes through the thalamus. Accurate
      identification of substructures of the thalamus is therefore of great importance
      for the understanding of human brain connectivity. Direct visualization of
      thalamic substructures, however, is not easily achieved with currently available
      magnetic resonance imaging (MRI), including ultra-high field MRI such as 7.0T,
      mainly due to the limited contrast between the relevant structures. Recently,
      improvements in ultra-high field 7.0T MRI have opened the possibility of
      observing thalamic substructures by well-adjusted high-resolution T1 -weighted
      imaging. Moreover, the recently developed super-resolution track-density imaging
      (TDI) technique, based on results from whole-brain fiber-tracking, produces
      images with sub-millimeter resolution. These two methods enable us to show
      markedly improved anatomical detail of the substructures of the thalamus,
      including their detailed locations and directionality. In this study, we
      demonstrate the role of TDI for the visualization of the substructures of the
      thalamic nuclei, and relate these images to T1-weighted imaging at 7.0T MRI.

PMID- 23151894
TI  - A technique to prevent duodenal blowout after difficult gastrectomies.
AB  - A simple technique of decompressing the duodenum following difficult
      gastrectomies is described which can be applied across the country to reduce the
      incidence of this serious complication. The procedure has been used in 120
      patients with no instance of duodenal blowout.

PMID- 23151895
TI  - Rectal histoplasmosis in Job's syndrome.

PMID- 23151893
TI  - Low-level laser therapy (LLLT) combined with swimming training improved the lipid
      profile in rats fed with high-fat diet.
AB  - Obesity and associated dyslipidemia is the fastest growing health problem
      throughout the world. The combination of exercise and low-level laser therapy
      (LLLT) could be a new approach to the treatment of obesity and associated
      disease. In this work, the effects of LLLT associated with exercises on the lipid
      metabolism in regular and high-fat diet rats were verified. We used 64 rats
      divided in eight groups with eight rats each, designed: SC, sedentary chow diet;
      SCL, sedentary chow diet laser, TC, trained chow diet; TCL, trained chow diet
      laser; SH, sedentary high-fat diet; SHL, sedentary high-fat diet laser; TH,
      trained high-fat diet; and THL, trained high-fat diet laser. The exercise used
      was swimming during 8 weeks/90 min daily and LLLT (GA-Al-As, 830 nm) dose of 4.7
      J/point and total energy 9.4 J per animal, applied to both gastrocnemius muscles
      after exercise. We analyzed biochemical parameters, percentage of fat, hepatic
      and muscular glycogen and relative mass of tissue, and weight percentage gain.
      The statistical test used was ANOVA, with post hoc Tukey-Kramer for multiple
      analysis between groups, and the significant level was p < 0.001, p < 0.01, and p
      < 0.05. LLLT decreased the total cholesterol (p < 0.05), triglycerides (p <
      0.01), low-density lipoprotein cholesterol (p < 0.05), and relative mass of fat
      tissue (p < 0.05), suggesting increased metabolic activity and altered lipid
      pathways. The combination of exercise and LLLT increased the benefits of exercise
      alone. However, LLLT without exercise tended to increase body weight and fat
      content. LLLT may be a valuable addition to a regimen of diet and exercise for
      weight reduction and dyslipidemic control. 

PMID- 23151896
TI  - Rectal perforation by impacted fecaloma--a new mechanism proposed.

PMID- 23151897
TI  - Adalimumab-induced psoriasis in a patient with Crohn's disease.

PMID- 23151899
TI  - Periventricular nodular heterotopia on prenatal ultrasound and magnetic resonance
      imaging.
AB  - OBJECTIVES: To describe the prenatal ultrasound and magnetic resonance imaging
      (MRI) findings suggestive of periventricular nodular heterotopia (PNH). METHODS:
      This retrospective case series included fetuses referred to our institution for
      brain MRI between 2007 and 2012, which were diagnosed with PNH and confirmed by
      postnatal MRI or autopsy. The type of PNH, associated ventriculomegaly and
      associated malformations are reported. RESULTS: We included 11 fetuses (nine
      female, two male) with a mean gestational age at diagnosis of 31 (range, 23-34)
      weeks. PNH lesions were small and diffuse (n = 7), large and multiple (n = 1) or
      single (n = 3). A targeted ultrasound examination performed before fetal MRI
      missed the diagnosis in four cases (one diffuse and three single); a further
      ultrasound examination performed after MRI diagnosed PNH in two of these four
      cases. Ventriculomegaly was present in six cases (four unilateral and two
      bilateral). PNH appeared in all cases as nodules of intermediate echogenicity
      protruding into the ventricular lumen. In all cases of diffuse PNH, the frontal
      horns and bodies of the lateral ventricles appeared square in shape on coronal
      view, with irregular borders on axial view. Associated cerebral malformations
      were observed in seven cases and included corpus callosal agenesis (n = 4, with
      additional malformations in two) and retrocerebellar cyst (n = 3). Extracerebral
      malformations were also present in two cases. Maternal MRI was performed in five
      of the six cases of isolated small and diffuse PNH in female fetuses, and
      demonstrated PNH in two of these. CONCLUSION: PNH is underdiagnosed at prenatal
      ultrasound, even on targeted scans. Irregular ventricular borders on axial view
      and irregular square-shaped lateral ventricles on coronal view are suggestive of
      PNH at prenatal ultrasound.

PMID- 23151898
TI  - Anticancer steroids: linking natural and semi-synthetic compounds.
AB  - Steroids, a widespread class of natural organic compounds occurring in animals,
      plants and fungi, have shown great therapeutic value for a broad array of
      pathologies. The present overview is focused on the anticancer activity of
      steroids, which is very representative of a rich structural molecular diversity
      and ability to interact with various biological targets and pathways. This review
      encompasses the most relevant discoveries on steroid anticancer drugs and leads
      through the last decade and comprises 668 references.

PMID- 23151900
TI  - Hyperexcitability of inferior colliculus neurons caused by acute noise exposure.
AB  - Noise exposure is one of the most common causes of hearing loss. Recent studies
      found that noise exposure-induced cochlear damage may change the excitability and
      tonotopic organization of the central auditory system (CAS). This plasticity was
      suspected to be related to tinnitus and hyperacusis. However, how cochlear damage
      affects CAS function and causes these neurologic diseases is still not clear. CAS
      function is activity dependent, so we hypothesize that a restricted cochlear
      lesion might disrupt the balance of excitation and inhibition in the CAS and
      thereby affect its neural activity. To test this hypothesis, we studied the
      effects of narrow-band noise exposure on the firing properties of neurons in the
      inferior colliculus (IC), which has complex neural circuits and plays an
      important role in sound processing. We found that noise exposure (20 kHz, 105 dB
      SPL, 30 min) caused a dramatic decrease of the characteristic frequency in about
      two-thirds of high-frequency neurons with/without causing a significant threshold
      shift. The noise exposure also caused an increase in firing rate of the low
      frequency neurons at suprathreshold levels, whereas it dramatically decreased the
      firing rate of the high-frequency neurons. Our results suggest that acute high
      frequency noise exposure may increase low-frequency responsiveness by causing
      hyperexcitability of low-frequency neurons. The functional change of the low
      frequency neurons may be related to the disruption of side-band inhibition at the
      noise exposure frequencies caused by cochlear damage.

PMID- 23151901
TI  - De novo design of a tumor-penetrating peptide.
AB  - Poor penetration of antitumor drugs into the extravascular tumor tissue is often
      a major factor limiting the efficacy of cancer treatments. Our group has recently
      described a strategy to enhance tumor penetration of chemotherapeutic drugs
      through use of iRGD peptide (CRGDK/RGPDC). This peptide comprises two sequence
      motifs: RGD, which binds to alphavbeta3/5 integrins on tumor endothelia and tumor
      cells, and a cryptic CendR motif (R/KXXR/K-OH). Once integrin binding has brought
      iRGD to the tumor, the peptide is proteolytically cleaved to expose the cryptic
      CendR motif. The truncated peptide loses affinity for its primary receptor and
      binds to neuropilin-1, activating a tissue penetration pathway that delivers the
      peptide along with attached or co-administered payload into the tumor mass. Here,
      we describe the design of a new tumor-penetrating peptide based on the current
      knowledge of homing sequences and internalizing receptors. The tumor-homing motif
      in the new peptide is the NGR sequence, which binds to endothelial CD13. The NGR
      sequence was placed in the context of a CendR motif (RNGR), and this sequence was
      embedded in the iRGD framework. The resulting peptide (CRNGRGPDC, iNGR) homed to
      tumor vessels and penetrated into tumor tissue more effectively than the standard
      NGR peptide. iNGR induced greater tumor penetration of coupled nanoparticles and
      co-administered compounds than NGR. Doxorubicin given together with iNGR was
      significantly more efficacious than the drug alone. These results show that a
      tumor-specific, tissue-penetrating peptide can be constructed from known sequence
      elements. This principle may be useful in designing tissue-penetrating peptides
      for other diseases.

PMID- 23151903
TI  - A preclinical mouse model of invasive lobular breast cancer metastasis.
AB  - Metastatic disease accounts for more than 90% of cancer-related deaths, but the
      development of effective antimetastatic agents has been hampered by the paucity
      of clinically relevant preclinical models of human metastatic disease. Here, we
      report the development of a mouse model of spontaneous breast cancer metastasis,
      which recapitulates key events in its formation and clinical course.
      Specifically, using the conditional K14cre;Cdh1(F/F);Trp53(F/F) model of de novo
      mammary tumor formation, we orthotopically transplanted invasive lobular
      carcinoma (mILC) fragments into mammary glands of wild-type syngeneic hosts. Once
      primary tumors were established in recipient mice, we mimicked the clinical
      course of treatment by conducting a mastectomy. After surgery, recipient mice
      succumbed to widespread overt metastatic disease in lymph nodes, lungs, and
      gastrointestinal tract. Genomic profiling of paired mammary tumors and distant
      metastases showed that our model provides a unique tool to further explore the
      biology of metastatic disease. Neoadjuvant and adjuvant intervention studies
      using standard-of-care chemotherapeutics showed the value of this model in
      determining therapeutic agents that can target early- and late-stage metastatic
      disease. In obtaining a more accurate preclinical model of metastatic lobular
      breast cancer, our work offers advances supporting the development of more
      effective treatment strategies for metastatic disease.

PMID- 23151902
TI  - Histone deacetylase inhibitor AR-42 differentially affects cell-cycle transit in
      meningeal and meningioma cells, potently inhibiting NF2-deficient meningioma
      growth.
AB  - Meningiomas constitute about 34% of primary intracranial tumors and are
      associated with increased mortality in patients with neurofibromatosis type 2
      (NF2). To evaluate potential medical therapies for these tumors, we have
      established a quantifiable orthotopic model for NF2-deficient meningiomas. We
      showed that telomerase-immortalized Ben-Men-1 benign meningioma cells harbored a
      single nucleotide deletion in NF2 exon 7 and did not express the NF2 protein,
      merlin. We also showed that AR-42, a pan-histone deacetylase inhibitor, inhibited
      proliferation of both Ben-Men-1 and normal meningeal cells by increasing
      expression of p16(INK4A), p21(CIP1/WAF1), and p27(KIP1). In addition, AR-42
      increased proapoptotic Bim expression and decreased anti-apoptotic Bcl(XL)
      levels. However, AR-42 predominantly arrested Ben-Men-1 cells at G(2)-M whereas
      it induced cell-cycle arrest at G(1) in meningeal cells. Consistently, AR-42
      substantially decreased the levels of cyclin D1, E, and A, and proliferating cell
      nuclear antigen in meningeal cells while significantly reducing the expression of
      cyclin B, important for progression through G(2), in Ben-Men-1 cells. In
      addition, AR-42 decreased Aurora A and B expression. To compare the in vivo
      efficacies of AR-42 and AR-12, a PDK1 inhibitor, we generated and used luciferase
      expressing Ben-Men-1-LucB cells to establish intracranial xenografts that grew
      over time. While AR-12 treatment moderately slowed tumor growth, AR-42 caused
      regression of Ben-Men-1-LucB tumors. Importantly, AR-42-treated tumors showed
      minimal regrowth when xenograft-bearing mice were switched to normal diet.
      Together, these results suggest that AR-42 is a potential therapy for
      meningiomas. The differential effect of AR-42 on cell-cycle progression of normal
      meningeal and meningioma cells may have implications for why AR-42 is well
      tolerated while it potently inhibits tumor growth.

PMID- 23151905
TI  - National trends in incidence rates of hospitalization for stroke in children with
      sickle cell disease.
AB  - BACKGROUND: The success of primary stroke prevention for children with sickle
      cell disease (SCD) throughout the United States is unknown. Therefore, we aimed
      to generate national incidence rates of hospitalization for stroke in children
      with sickle cell disease (SCD) before and after publication of the Stroke
      Prevention Trial in Sickle Cell Anemia (STOP trial) in 1998. PROCEDURE: We
      performed a retrospective trend analysis of the 1993-2009 Nationwide Inpatient
      Sample and Kids' Inpatient Databases. Hospitalizations for SCD patients 0-18
      years old with stroke were identified by ICD-9CM code. The primary outcome, the
      trend in annual incidence rate of hospitalization for stroke in children with
      SCD, was analyzed by linear regression. Incidence rates of hospitalization for
      stroke before and after 1998 were compared by the Wilcoxon rank-sum test.
      RESULTS: From 1993 to 2009, 2,024 hospitalizations were identified for stroke.
      Using the mean annual incidence rate of hospitalization for stroke from 1993 to
      1998 as the baseline, the rate decreased from 1993 to 2009 (point estimate = 
      0.022/100 patient years [95% CI, -0.039, -0.005], P = 0.027). The mean annual
      incidence rate of hospitalization stroke decreased by 45% from 0.51 per 100
      patient years in 1993-1998 to 0.28 per 100 patient years in 1999-2009 (P =
      0.008). Total hospital days and charges attributed to stroke also decreased by
      45% and 24%, respectively. CONCLUSIONS: After publication of the STOP trial and
      hydroxyurea licensure in 1998, the incidence of hospitalization for stroke in
      children with SCD decreased across the United States, suggesting that primary
      stroke prevention has been effective nationwide, but opportunity for improvement
      remains.

PMID- 23151904
TI  - Targeting truncated retinoid X receptor-alpha by CF31 induces TNF-alpha-dependent
      apoptosis.
AB  - A truncated version of retinoid X receptor-alpha, tRXR-alpha, promotes cancer
      cell survival by activating the phosphoinositide 3-kinase (PI3K)/AKT pathway.
      However, targeting the tRXR-alpha-mediated survival pathway for cancer treatment
      remains to be explored. We report here our identification of a new natural
      product molecule, CF31, a xanthone isolated from Cratoxylum formosum ssp.
      pruniflorum, and the biologic evaluation of its regulation of the tRXR-alpha
      mediated PI3K/AKT pathway. CF31 binds RXR-alpha and its binding results in
      inhibition of RXR-alpha transactivation. Through RXR-alpha mutational analysis
      and computational studies, we show that Arg316 of RXR-alpha, known to form salt
      bridges with certain RXR-alpha ligands, such as 9-cis-retinoic acid (9-cis-RA),
      is not required for the antagonist effect of CF31, showing a distinct binding
      mode. Evaluation of several CF31 analogs suggests that the antagonist effect is
      mainly attributed to an interference with Leu451 of helix H12 in RXR-alpha. CF31
      is a potent inhibitor of AKT activation in various cancer cell lines. When
      combined with TNF-alpha, it suppresses TNF-alpha activation of AKT by inhibiting
      TNF-alpha-induced tRXR-alpha interaction with the p85alpha regulatory subunit of
      PI3K. CF31 inhibition of TNF-alpha activation of AKT also results in TNF-alpha
      dependent activation of caspase-8 and apoptosis. Together, our results show that
      CF31 is an effective converter of TNF-alpha signaling from survival to death by
      targeting tRXR-alpha in a unique mode and suggest that identification of a
      natural product that targets an RXR-mediated cell survival pathway that regulates
      PI3K/AKT may offer a new therapeutic strategy to kill cancer cells.

PMID- 23151906
TI  - Comparative study of three Plumbago L. species (Plumbaginaceae) by microscopy,
      UPLC-UV and HPTLC.
AB  - This paper presents a comparative study of anatomy of leaves, stems and roots of
      three species of Plumbago, namely P. auriculata Lam., P. indica L. and P.
      zeylanica L. by light microscopy. The paper also provides qualitative and
      quantitative analysis of the naphthoquinone, plumbagin-a major constituent
      present in these species-using UPLC-UV. Microscopic examinations revealed the
      presence of distinctive differences in the anatomical features of the leaf, stem
      and root of the three species, and these can thus be used for identification and
      authentication of these species. UPLC-UV analysis showed the highest
      concentration of plumbagin in the roots of P. zeylanica (1.62% w/w) followed by
      the roots of P. indica (0.97% w/w) and then P. auriculata (0.33-0.53% w/w). In
      contrast, plumbagin was not detected in the stems and leaves of P. indica and in
      the leaves of P. auriculata, whereas very low concentrations (<0.02% w/w) of
      plumbagin were detected in the stems and leaves of P. zeylanica and in the stems
      of P. auriculata. HPTLC fingerprints of the leaf and root of the three species
      exhibited distinguishable profiles, while those of the stems were
      undifferentiated.

PMID- 23151907
TI  - Polypharmacy (herbal and synthetic drug combination): a novel approach in the
      treatment of type-2 diabetes and its complications in rats.
AB  - The aim of present study was to evaluate the effect of aqueous leaf extract of
      Annona squamosa with Glipizide in a high fat diet and streptozocin-induced type-2
      diabetes. Nine groups (n = 6) of male Sprague-Dawley rats were used for the
      study, with. Basal blood glucose, urine volume, and body weights were measured
      and the rate were kept on a high fat diet. After 15 days, streptozocin in sub
      diabetic dose (35 mg/kg) was administered to the animals to induce diabetes. With
      1 week of consistent hyperglycemia, treatment was initiated. Aqueous extract of
      Annona squamosa was administered orally at 350 mg/kg body weight alone and in
      combination with reduced and reducing dose combinations of Glipizide. Blood
      glucose, body weight, urine volume were measured every 10th day. The elevated
      blood-glucose level in diabetic rats was controlled better with combination
      therapy compared with the synthetic drug alone or the herbal stand-alone drug.
      All the results were statistically significant (P < 0.001). A combination of
      Annona squamosa along with Glipizide may be helpful in dose reduction of
      Glipizide up to 50%, reducing the risk of the onset of insulin therapy.

PMID- 23151908
TI  - Ophiopogonin B-induced autophagy in non-small cell lung cancer cells via
      inhibition of the PI3K/Akt signaling pathway.
AB  - Ophiopogonin B (OP-B) is a bioactive component of Radix Ophiopogon Japonicus,
      which is often used in Chinese traditional medicine to treat pulmonary disease.
      However, whether or not OP-B has any potential antitumor activity has not been
      reported. Here, we show that the non-small cell lung cancer (NSCLC) cell lines
      NCI-H157 and NCI-H460 treated with OP-B grow more slowly and accumulate vacuoles
      in their cytoplasm compared to untreated control cells. Flow cytometric analysis
      showed that the cells were arrested in G0/G1 phase. Nuclear morphology, Annexin
      V/PI staining, and expression of cleaved caspase-3 all confirm that OP-B does not
      induce apoptosis. Instead, based on results from both transmission electron
      microscopy (TEM) and the expression of microtubule-associated protein 1 light
      chain 3-II (LC3-II), we determined that OP-B treatment induced autophagy in both
      cell lines. Next, we examined the PI3K/Akt/mTOR signaling pathway and found that
      OP-B inhibited phosphorylation of Akt (Ser473, Thr308) in NCI-H157 cells and also
      inhibited several key components of the pathway in NCI-H460 cells, such as p
      Akt(Ser473, Thr308), p-p70S6K (Thr389). Additionally, insulin-mediated activation
      of the PI3K/Akt/mTOR pathway provides evidence that activation of this pathway
      may correlate with induction of autophagy in H460 cells. Therefore, OP-B is a
      prospective inhibitor of PI3K/Akt and may be used as an alternative compound to
      treat NSCLC.

PMID- 23151909
TI  - 1,25-Dihydroxy vitamin D and coronary microvascular function.
AB  - PURPOSE: The active form of vitamin D (1,25(OH)(2)D) contributes to blood flow
      regulation in skeletal muscle. The aim of the present study was to determine
      whether this hormone also modulates coronary physiology, and thus whether
      abnormalities in its bioavailability contribute to excess cardiovascular risk in
      patients with disorders of mineral metabolism. METHODS: As a clinical model of
      the wide variability in 1,25(OH)(2)D bioavailability, we studied 23 patients (62
      +/- 8 years) with suspected primary hyperparathyroidism referred for myocardial
      perfusion imaging because of atypical chest pain and at least one cardiovascular
      risk factor. Dipyridamole and baseline myocardial blood flow indexes were
      assessed on G-SPECT imaging of (99m)Tc-tetrofosmin, with normalization of the
      myocardial count rate to the corresponding first-transit counts in the pulmonary
      artery. Coronary flow reserve (CFR) was defined as the ratio between dipyridamole
      and baseline myocardial blood flow indexes. In all patients, parathyroid hormone,
      25-hydroxy vitamin D (25(OH)D) and 1,25(OH)(2)D serum levels were determined.
      RESULTS: Primary hyperparathyroidism was eventually diagnosed in 15 of the 23
      patients. The mean 25(OH)D concentration was relatively low (21 +/- 10 ng/mL)
      while the concentrations of 1,25(OH)(2)D varied widely but within the normal
      range (mean 95 +/- 61 pmol/L). No patient showed reversible perfusion defects on
      G-SPECT. CFR was not correlated with either the serum concentration of 25(OH)D
      nor that of parathyroid hormone, but was strictly correlated with the serum level
      of 1,25(OH)(2)D (R = 0.8, p < 0.01). Moreover, patients with a 1,25(OH)(2)D
      concentration below the median value (86 pmol/L) had markedly lower CFR than the
      other patients (1.48 +/- 0.40 vs. 2.51 +/- 0.63, respectively; p < 0.001).
      CONCLUSION: Bioavailable 1,25(OH)(2)D modulates coronary microvascular function.
      This effect might contribute to the high cardiovascular risk of conditions
      characterized by chronic reduction in bioavailability of this hormone.

PMID- 23151910
TI  - (11)C-Choline PET/CT in patients with hormone-resistant prostate cancer showing
      biochemical relapse after radical prostatectomy.
AB  - PURPOSE: To determine the diagnostic efficacy of (11)C-choline PET/CT in patients
      with prostate cancer (PC) after radical prostatectomy who presented with
      increasing PSA levels during follow-up in spite of being on hormone treatment
      (HT), and therefore showing HT resistance. METHODS: We evaluated a large series
      of 157 consecutive PC patients previously treated by radical prostatectomy who
      presented with biochemical recurrence with increasing PSA levels in spite of
      ongoing HT (HT-resistant patients). At the time of (11)C-choline PET/CT, the mean
      value of trigger PSA level was 8.3 (range 0.2 - 60.6 ng/mL), the mean PSA
      doubling time (PSAdt) was 5.3 (range 0.4 - 35 months), and the mean PSA velocity
      (PSAvel) was 22.1 ng/mL/year (range 0.12 - 82 ng/mL/year). (11)C-Choline PET/CT
      was performed following a standard procedure at our centre to investigate
      increasing PSA levels, either as the first imaging procedure or in patients with
      negative conventional imaging. At the time of (11)C-choline PET/CT all patients
      were receiving HT (61 were receiving monotherapy and 96 multidrug therapy). PET
      positive findings were validated by: (a) transrectal US-guided biopsy in patients
      with recurrence in the prostatic bed, (b) surgical pelvic lymphadenectomy, (c)
      other imaging modalities, including repeated (11)C-choline PET/CT, performed
      during a minimum follow-up of 12-months. RESULTS: (11)C-Choline PET/CT showed
      positive findings in 104 of the 157 patients (66 %). (11)C-choline PET/CT
      detected: a single lesion in 40 patients (7 in the prostate bed, 10 in lymph
      nodes, 22 in bone, 1 at another site); two lesions in 18 patients (7 in lymph
      nodes, 7 in bone, 4 in both lymph nodes and bone); three or four lesions in 7
      patients (4 in lymph nodes, 2 in bone, 1 at another site); and more than four
      lesions in the remaining 39 patients (2 in the prostate bed, 12 in lymph nodes,
      12 in bone, 11 in both lymph nodes and bone, 2 at other sites). In (11)C-choline
      PET-negative patients, the mean values of trigger PSA, PSAdt and PSAvel were 3.8
      ng/mL (range 0.2-11.9 ng/mL) 7.0 months (range 1.21 - 35 months) and 5.8
      ng/mL/year (range 0.12 - 30.1) respectively, while in (11)C-Choline-PET-positive
      patients they were 10.5 ng/mL (range 0.2 - 60.6), 4.4 months (range 0.4 - 19.7)
      and 15.9 ng/mL/year (range 0.5 - 82.0) respectively. The differences between PET
      negative and PET-positive patients were statistically significant for all these
      parameters: trigger PSA, p < 0.01; PSAdt, p < 0.01; PSAvel, p = 0.03. CONCLUSION:
      In our patient population, (11)C-choline PET/CT was able to detect relapsed
      disease in a large proportion of HT-resistant PC patients during HT. These data,
      obtained in a large series, suggest that HT withdrawal before performing a (11)C
      choline PET/CT scan may not be necessary for the detection of recurrent disease
      if PSA levels are increasing and PSA kinetics are rapid.

PMID- 23151911
TI  - Comparison of PET metabolic indices for the early assessment of tumour response
      in metastatic colorectal cancer patients treated by polychemotherapy.
AB  - PURPOSE: To compare the performance of eight metabolic indices for the early
      assessment of tumour response in patients with metastatic colorectal cancer
      (mCRC) treated with chemotherapy. METHODS: Forty patients with advanced mCRC
      underwent two FDG PET/CT scans, at baseline and on day 14 after chemotherapy
      initiation. For each lesion, eight metabolic indices were calculated: four
      standardized uptake values (SUV) without correction for the partial volume effect
      (PVE), two SUV with correction for PVE, a metabolic volume (MV) and a total
      lesion glycolysis (TLG). The relative change in each index between the two scans
      was calculated for each lesion. Lesions were also classified as responding and
      nonresponding lesions using the Response Evaluation Criteria In Solid Tumours
      (RECIST) 1.0 measured by contrast-enhanced CT at baseline and 6-8 weeks after
      starting therapy. Bland-Altman analyses were performed to compare the various
      indices. Based on the RECIST classification, ROC analyses were used to determine
      how accurately the indices predicted lesion response to therapy later seen with
      RECIST. RESULTS: RECIST showed 27 responding and 74 nonresponding lesions. Bland
      Altman analyses showed that the four SUV indices uncorrected for PVE could not be
      used interchangeably, nor could the two SUV corrected for PVE. The areas under
      the ROC curves (AUC) were not significantly different between the SUV indices not
      corrected for PVE. The mean SUV change in a lesion better predicted lesion
      response without than with PVE correction. The AUC was significantly higher for
      SUV uncorrected for PVE than for the MV, but change in MV provided some
      information regarding the lesion response to therapy (AUC >0.5). CONCLUSION: In
      these mCRC patients, all SUV uncorrected for PVE accurately predicted the tumour
      response on day 14 after starting therapy as assessed 4 to 6 weeks later (i.e. 6
      to 8 weeks after therapy initiation) using the RECIST criteria. Neither
      correcting SUV for PVE nor measuring TLG improved the assessment of tumour
      response compared to SUV uncorrected for PVE. The change in MV was the least
      accurate index for predicting tumour response.

PMID- 23151912
TI  - Clinical usefulness of breast-specific gamma imaging as an adjunct modality to
      mammography for diagnosis of breast cancer: a systemic review and meta-analysis.
AB  - PURPOSE: The purpose of this study was to assess the diagnostic performance of
      breast-specific gamma imaging (BSGI) as an adjunct modality to mammography for
      detecting breast cancer. METHODS: Comprehensive searches of MEDLINE (1984 to
      August 2012) and EMBASE (1994 to August 2012) were performed. A summary receiver
      operating characteristic curve (SROC) was constructed to summarize the overall
      test performance of BSGI. The sensitivities for detecting subcentimetre cancer
      and ductal carcinoma in situ (DCIS) were pooled. The potential of BSGI to
      complement mammography was also evaluated by identifying mammography-occult
      breast cancer. RESULTS: Analysis of the studies revealed that the overall
      validity estimates of BSGI in detecting breast cancer were as follows:
      sensitivity 95 % (95 % CI 93-96 %), specificity 80 % (95 % CI 78-82 %), positive
      likelihood ratio 4.63 (95 % CI 3.13-6.85), negative likelihood ratio 0.08 (95 %
      CI 0.05-0.14), and diagnostic odds ratio 56.67 (95 % CI 26.68-120.34). The area
      under the SROC was 0.9552 and the Q* point was 0.8977. The pooled sensitivities
      for detecting subcentimetre cancer and DCIS were 84 % (95 % CI 80-88 %) and 88 %
      (95 % CI 81-92 %), respectively. Among patients with normal mammography, 4 % were
      diagnosed with breast cancer by BSGI, and among those with mammography suggestive
      of malignancy or new biopsy-proven breast cancer, 6 % were diagnosed with
      additional cancers in the breast by BSGI. CONCLUSION: BSGI had a high diagnostic
      performance as an excellent adjunct modality to mammography for detecting breast
      cancer. The ability to identify subcentimetre cancer and DCIS was also high.

PMID- 23151913
TI  - Predictive and prognostic value of metabolic tumour volume and total lesion
      glycolysis in solid tumours.
AB  - Data available in patients suffering from squamous cell carcinoma of the head and
      neck, lung carcinoma, oesophageal carcinoma and gynaecological malignancies
      suggest that metabolic tumour volume and to a lesser extent total lesion
      glycolysis have the potential to become valuable in the imaging of human solid
      tumours as prognostic biomarkers for short- to intermediate-term survival
      outcomes, adding value to clinical staging, for assessment of response to
      treatment with neoadjuvant and concurrent chemotherapy, and for treatment
      optimization; for example, based on early treatment response assessment using
      changes in metabolic tumour volume over time, it might be possible to select
      patients who require a more aggressive treatment to improve their outcome.
      Prospective studies enrolling consecutive patients, adopting standardized
      protocols for FDG PET acquisition and processing, adjusting for potential
      confounders in the analysis (tumour size and origin) and determining the optimal
      methodology for determination of these novel markers are mandatory.

PMID- 23151914
TI  - Performance of orthopantomography, planar scintigraphy, CT alone and SPECT/CT in
      patients with suspected osteomyelitis of the jaw.
AB  - PURPOSE: The aim of this study was to evaluate the performance of a novel flat
      panel single photon emission computed tomography (SPECT)/CT in patients with
      suspicion of osteomyelitis (OM) of the jaw in comparison with conventional
      orthopantomography (OPT), planar bone scintigraphy (PS) and CT alone. METHODS:
      Forty-two patients (21 female, 21 male, mean age 52, range 10-84 years) with
      suspected OM (n = 38) or exacerbation of a known OM (n = 4) were investigated
      with OPT, CT alone, PS and combined SPECT/CT. Images were separately reviewed by
      a nuclear physician/radiologist and jaw surgeon regarding presence of OM.
      Additionally, the different methods were rated regarding their usefulness for
      diagnosis (5-point scale: from 1 = diagnostic to 5 = useless). Biopsy served as
      the standard of reference in 30 patients and clinical/imaging follow-up of at
      least 6 months in 12 patients. RESULTS: In 35 of 42 patients the final diagnosis
      of OM was established according to the reference standard. Sensitivity,
      specificity and accuracy for OPT was 59, 100 and 66 %, for CT alone 77, 86 and 79
      %, for PS 100, 71 and 95 % and for SPECT/CT 100, 86 and 98 %. SPECT/CT was
      significantly more accurate compared with CT alone (p = 0.0078) and OPT (p =
      0.001). SPECT/CT was rated as the most useful imaging modality (mean value 1.2)
      compared with PS (2.2), CT (2.5) and OPT (3.2). CONCLUSION: SPECT/CT is an
      accurate method to assess the presence of OM of the jaw and superior to CT alone
      and OPT. SPECT/CT slightly improved the specificity of PS. However, SPECT/CT in
      this study was not significantly more accurate compared with PS and whether the
      advantages to the patient of a one-stop study as opposed to doing separate CT and
      PS justifies its routine use in terms of cost requires further study.

PMID- 23151915
TI  - Somatostatin receptor PET in neuroendocrine tumours: 68Ga-DOTA0,Tyr3-octreotide
      versus 68Ga-DOTA0-lanreotide.
AB  - PURPOSE: The aim of this study was to evaluate the impact of (68)Ga-labelled
      DOTA(0)-lanreotide ((68)Ga-DOTA-LAN) on the diagnostic assessment of
      neuroendocrine tumour (NET) patients with low to moderate uptake on planar
      somatostatin receptor (SSTR) scintigraphy or (68)Ga-labelled DOTA(0),Tyr(3)
      octreotide ((68)Ga-DOTA-TOC) positron emission tomography (PET). METHODS: Fifty
      three patients with histologically confirmed NET and clinical signs of
      progressive disease, who had not qualified for peptide receptor radionuclide
      therapy (PRRT) on planar SSTR scintigraphy or (68)Ga-DOTA-TOC PET (n = 38) due to
      lack of tracer uptake, underwent (68)Ga-DOTA-LAN PET to evaluate a treatment
      option with (90)Y-labelled lanreotide according to the MAURITIUS trial. The
      included patients received 150 +/- 30 MBq of each radiopharmaceutical
      intravenously. PET scans were acquired 60-90 min after intravenous bolus
      injection. Image results from both PET scans were compared head to head, focusing
      on the intensity of tracer uptake in terms of treatment decision. CT was used for
      morphologic correlation of tumour lesions. To further evaluate the binding
      affinities of each tracer, quantitative and qualitative values were calculated
      for target lesions. RESULTS: (68)Ga-DOTA-LAN and (68)Ga-DOTA-TOC both showed
      equivalent findings in 24/38 patients when fused PET/CT images were interpreted.
      The sensitivity, specificity and accuracy of (68)Ga-DOTA-LAN in comparison to CT
      were 0.63, 0.5 and 0.62 (n = 53; p < 0.0001) and for (68)Ga-DOTA-TOC in
      comparison to CT 0.78, 0.5 and 0.76 (n = 38; p < 0.013), respectively. (68)Ga
      DOTA-TOC showed a significantly higher maximum standardized uptake value
      (SUV(max)) regarding the primary tumour in 25 patients (p < 0.003) and regarding
      the liver in 30 patients (p < 0.009) compared to (68)Ga-DOTA-LAN. Corresponding
      values of both PET scans for tumour and liver did not show any significant
      correlation. (68)Ga-DOTA-TOC revealed more tumour sites than (68)Ga-DOTA-LAN (106
      vs 53). The tumour to background ratios for tumour and liver calculated from
      SUV(max) measurements were significantly higher for (68)Ga-DOTA-TOC than (68)Ga
      DOTA-LAN (p < 0.02). CONCLUSION: (68)Ga-DOTA-TOC PET imaging is an established
      imaging procedure for accurate staging of NET patients. (68)Ga-DOTA-LAN should
      only be considered as a PET tracer of second choice in patients with no
      pathologic tracer uptake on (68)Ga-DOTA-TOC PET. In these patients, (68)Ga-DOTA
      LAN PET can provide valuable information when evaluating PRRT as the treatment
      option, as a broader spectrum of human SSTR subtypes can be detected.

PMID- 23151916
TI  - Marked inhibition of Na+, K(+)- ATPase activity and the respiratory chain by
      phytanic acid in cerebellum from young rats: possible underlying mechanisms of
      cerebellar ataxia in Refsum disease.
AB  - Refsum disease is an autosomal recessive disorder of peroxisomal metabolism
      biochemically characterized by highly elevated concentrations of phytanic acid
      (Phyt) in a variety of tissues including the cerebellum. Reduction of plasma Phyt
      levels by dietary restriction intake ameliorates ataxia, a common clinical
      manifestation of this disorder, suggesting a neurotoxic role for this branched
      chain fatty acid. Therefore, considering that the underlying mechanisms of
      cerebellum damage in Refsum disease are poorly known, in the present study we
      tested the effects of Phyt on important parameters of bioenergetics, such as the
      activities of the respiratory chain complexes I to IV, creatine kinase and Na(+),
      K(+)- ATPase in cerebellum preparations from young rats. The activities of
      complexes I, II, I-III and II-III and Na(+), K(+)- ATPase were markedly inhibited
      (65-85%) in a dose-dependent manner by Phyt. In contrast, creatine kinase and
      complex IV activities were not altered by this fatty acid. Therefore, it is
      presumed that impairment of the electron flow through the respiratory chain and
      inhibition of Na(+), K(+)- ATPase that is crucial for synaptic function may be
      involved in the pathophysiology of the cerebellar abnormalities manifested as
      ataxia in Refsum disease and in other peroxisomal disorders in which brain Phyt
      accumulates.

PMID- 23151917
TI  - The dual PI3K/mTOR inhibitor NVP-BEZ235 and chloroquine synergize to trigger
      apoptosis via mitochondrial-lysosomal cross-talk.
AB  - On the basis of our previous identification of aberrant phosphatidylinositol-3
      kinase (PI3K)/Akt signaling as a novel poor prognostic factor in neuroblastoma,
      we evaluated the dual PI3K/mTOR inhibitor BEZ235 in the present study. Here,
      BEZ235 acts in concert with the lysosomotropic agent chloroquine (CQ) to trigger
      apoptosis in neuroblastoma cells in a synergistic manner, as calculated by
      combination index (CI < 0.5). Surprisingly, inhibition of BEZ235-induced
      autophagy is unlikely the primary mechanism of this synergism as reported in
      other cancers, since neither inhibition of autophagosome formation by knockdown
      of Atg7 or Atg5 nor disruption of the autophagic flux by Bafilomycin A1 (BafA1)
      enhance BEZ235-induced apoptosis. BEZ235 stimulates enlargement of the lysosomal
      compartment and generation of reactive oxygen species (ROS), while CQ promotes
      lysosomal membrane permeabilization (LMP). In combination, BEZ235 and CQ
      cooperate to trigger LMP, Bax activation, loss of mitochondrial membrane
      potential (MMP) and caspase-dependent apoptosis. Lysosome-mediated apoptosis
      occurs in a ROS-dependent manner, as ROS scavengers significantly reduce
      BEZ235/CQ-induced loss of MMP, LMP and apoptosis. There is a mitochondrial
      lysosomal cross-talk, since lysosomal enzyme inhibitors significantly decrease
      BEZ235- and CQ-induced drop of MMP and apoptosis. In conclusion, BEZ235 and CQ
      act in concert to trigger LMP and lysosome-mediated apoptosis via a mitochondrial
      lysosomal cross-talk. These findings have important implications for the rational
      development of PI3K/mTOR inhibitor-based combination therapies.

PMID- 23151918
TI  - Investigation of the biological properties of (hetero)aromatic
      thiosemicarbazones.
AB  - Two series of thiosemicarbazone-based iron chelators (twenty-seven compounds)
      were designed and synthesized using a microwave-assisted approach. Quinoline and
      halogenated phenyl were selected as parent scaffolds on the basis of a similarity
      search. The lipophilicity of the synthesized compounds was measured using HPLC
      and then calculated. Primary in vitro screening of the synthesized compounds was
      performed against eight pathogenic fungal strains. Only a few compounds showed
      moderate activity against fungi, and (E)-2-(quinolin-2-ylvinyl)-N,N
      dimethylhydrazine-carbothioamide appeared to be more effective than fluconazole
      against most of the fungal strains tested. Antiproliferative activity was
      measured using a human colon cancer cell line (HCT-116). Several of the tested
      compounds showed submicromolar antiproliferative activity. Compounds were also
      tested for their activity related to the inhibition of photosynthetic electron
      transport (PET) in spinach (Spinacia oleracea L.) chloroplasts. The structure
      activity relationships are discussed for all of the compounds.

PMID- 23151919
TI  - Therapeutic applications of nucleic acids and their analogues in Toll-like
      receptor signaling.
AB  - Toll-like receptors (TLRs) belong to a family of innate immune receptors that
      detect and clear invading microbial pathogens. Specifically intracellular TLRs
      such as TLR3, TLR7, TLR8 and TLR9 recognize nucleic acids such as double-stranded
      RNA, single-stranded RNA and CpG DNA respectively derived from microbial
      components. Upon infection, nucleic acid sensing TLRs signal within endosomal
      compartment triggering the induction of essential proinflammatory cytokines and
      type I interferons to initiate innate immune responses thereby leading to a
      critical role in the development of adaptive immune responses. Thus, stimulation
      of TLRs by nucleic acids is a promising area of research for the development of
      novel therapeutic strategies against pathogenic infection, allergies, malignant
      neoplasms and autoimmunity. This review summarizes the therapeutic applications
      of nucleic acids or nucleic acid analogues through the modulation of TLR
      signaling pathways.

PMID- 23151920
TI  - Is the Maternal and Child Health (MCH) handbook effective in improving health
      related behavior? Evidence from Palestine.
AB  - OBJECTIVE: This study examines the effect of the Maternal and Child Health (MCH)
      handbook--a home-based health record--on women's knowledge and behavior in the
      Jericho and Ramallah Governorates of Palestine. METHODS: This study uses a
      repeated, cross-sectional data set in which pre- and post-intervention situations
      are incorporated on two groups: those exposed and those not exposed to the MCH
      handbook. We employed a difference-in-difference regression analysis utilizing a
      pre-tested knowledge, attitude, and practice survey of women at 24 MCH
      'treatment' centers (N=260, 270, pre-/post-) in comparison with the women at 6
      MCH centers (N=70, 70, pre-/post-) where the MCH handbook was not released. A
      trained facilitator conducted a series of focus group discussions with 42 women
      who were the clients of MCH services and 25 health providers, both from the
      intervention area, to confirm the results obtained from the quantitative study.
      FINDINGS: Knowledge related to MCH such as the importance of exclusive
      breastfeeding and how to cope with the risks of rupture of membranes during
      pregnancy increased among MCH handbook users, especially among less-educated
      women. The MCH handbook may be an effective tool for communication with health
      providers and husbands, for both highly educated and less-educated women during
      their first pregnancy. Our results suggest that although less-educated women
      rarely read the handbook themselves at home, they became familiar with health
      information and options related to MCH through personalized guidance that was
      provided by health providers at health facilities utilizing MCH handbook.
      CONCLUSION: The MCH handbook may be an effective tool to improve (i)
      communication between the client and the health provider and (ii) women's
      knowledge- and health-seeking behaviors related to maternal, newborn, and child
      health.

PMID- 23151921
TI  - Community-based HIV prevention interventions that combat anti-gay stigma for men
      who have sex with men and for transgender women.
AB  - Men who have sex with men (MSM) have been disproportionately affected by HIV
      since the onset of the epidemic. Public health discourse about prevention has
      traditionally focused on individual risk behavior and less on the socio
      structural factors that place MSM at increased risk of infection. Anti-gay bias
      and stigma are key structural drivers of HIV and must therefore be treated as a
      public health threat. Community-based prevention intervention programs that
      affirm the healthy formation of gay and transgender identities are strongly
      needed. Gay affirming school-based interventions and resiliency-focused social
      marketing campaigns have shown positive impact on health outcomes and should be
      implemented on a broader scale to challenge anti-gay stigma.

PMID- 23151922
TI  - Transformational leadership and navigating change.

PMID- 23151923
TI  - Influencing the language of nursing: an interview with T. Heather Herdman and Sue
      Moorhead. Interview by Jeffrey M. Adams.
AB  - This department highlights nursing leaders who have demonstrated a commitment to
      leading change. This interview profiles the experiences and insights of nursing
      language standardization leaders T. Heather Herdman, PhD, RN, FNI, the
      CEO/executive director of NANDA-I, and Sue Moorhead, PhD, RN, FNI, the director
      of the Center for Nursing Classification and Clinical Effectiveness and associate
      professor at the University of Iowa, College of Nursing.

PMID- 23151924
TI  - The challenges of nurse-physician communication: a review of the evidence.

PMID- 23151925
TI  - How resilient are your team members?
AB  - This department highlights change management strategies that may be successful in
      strategically planning and executing organizational change initiatives. With the
      goal of presenting practical approaches helpful to nurse leaders advancing
      organizational change, content includes evidence-based projects, tools, and
      resources that mobilize and sustain organizational change initiatives. In this
      article, the author explores personal resilience as an important individual
      characteristic that affects team functioning and thus organizational adaptability
      to change. The important role of resilience in strategic leadership for change is
      presented along with suggestions for evaluating and developing resilience.

PMID- 23151926
TI  - Academic-practice partnerships fuel future success.

PMID- 23151927
TI  - A new window into nurse manager development: teaching for the practice.
AB  - An important domain that emerged from the interpretation of 91 nurse manager (NM)
      narratives was achieving the right relationship between a NM and a recalcitrant
      staff member. This article depicts the qualitative distinctions in 2 stages of NM
      practice to show the importance of reflection on experiential learning in the
      development of expertise. This work confirms that NM development is more complex
      than teaching a curriculum of business and management theory and should include
      teaching for mastery of the skilled know-how of clinical leadership practice and
      formation of the person as manager.

PMID- 23151928
TI  - Bar-code verification: reducing but not eliminating medication errors.
AB  - Using observation, eye tracking, and clinical simulation with embedded errors, we
      studied the impact of bar-code verification on error identification and recovery
      during medication administration. Data supported that bar-code verification may
      reduce but does not eliminate patient identification (ID) and medication errors
      during clinical simulation of medication administration.

PMID- 23151929
TI  - A longitudinal analysis of nursing specialty certification by Magnet(r) status
      and patient unit type.
AB  - The objective of this study was to examine nursing specialty certification trends
      by Magnet(r) status and unit type. Research exploring organizational and unit
      attributes associated with higher specialty certification rates is timely given
      the beginning evidence that certification is associated with lower patient
      adverse events. The sample included 6047 units in 1249 National Database of
      Nursing Quality Indicators hospitals. Hierarchical linear modeling was used to
      predict growth in percentage of specialty-certified RNs within each unit type and
      Magnet status. Data (Bayesian Information Criteria = 224 583.30) demonstrated
      significant growth in specialty certification rates over time (P < .0001). Magnet
      designated organizations had significantly different starting certification rates
      (P = .0002) and rates of change (P = .0002). Unit types also had significantly
      different starting certification rates (P < .0001) and different rates of change
      (P < .0001). Magnet recognition is associated with increases in specialty
      certification rates. Certification rates have risen faster in unit types such as
      pediatric critical care than in unit types such as adult step-down and adult
      surgical.

PMID- 23151930
TI  - Engagement in RNs working in Magnet(r)-designated hospitals: exploring the
      significance of work experience.
AB  - This study analyzed and evaluated the relationships between work engagement (WE)
      and work experience among acute-care RNs in Magnet(r)-designated hospitals. The
      organizational structures of Magnet-designated hospitals are recognized to
      promote RN engagement, yet limited knowledge exists on engendering engagement to
      the same degree in all nurses. The study used a descriptive, correlational
      design. A convenience sample of RNs (n = 220) completed 2 surveys to measure WE,
      RN experience, and unit longevity (years of experience in the current setting).
      Significant relationships were found between WE and RN experience in any setting,
      within the consistent organizational structures of Magnet-designated hospitals.
      This study highlights the importance of organizational structures and the
      significance of RN experience in creating engagement among nurses. Enhancing
      engagement in the RN workforce facilitates retention and improved outcomes for
      patients, nurses, and organizations.

PMID- 23151932
TI  - Decisional involvement in Magnet(r), magnet-aspiring, and non-magnet hospitals.
AB  - BACKGROUND: Empowered decision making can help establish innovative work
      cultures. OJECTIVE: This study used the Decisional Involvement Scale to determine
      differences in actual and preferred decisional involvement among staff RNs and
      administrators in Magnet(r), Magnet-aspiring, and non-Magnet hospitals. METHODS:
      : Two facilities were Magnet designated, 3 were Magnet aspiring, and 9 were non
      Magnet. A total of 5000 staff RNs and administrators were asked to participate in
      the nonexperimental descriptive survey. RESUTS: The difference observed in actual
      global scale score by Magnet status was statistically significant (P = .01).
      Respondents in Magnet hospitals had the highest actual global scale score on
      average, followed by Magnet-aspiring, then non-Magnet. CONCLUSIONS: Decisional
      involvement is higher among Magnet-designated than non-Magnet facilities.

PMID- 23151931
TI  - Quality outcomes of hospital supplemental nurse staffing.
AB  - Use of supplemental RNs (SRNs) is common practice among US hospitals to fill gaps
      in nurse staffing. The objective of this study was to examine the relationship
      between use of SRNs and patient outcomes. Multilevel modeling was performed to
      analyze hospital administrative data from 19 hospital units in a large tertiary
      medical center for the years 2003 to 2006. Patient outcomes included in-hospital
      mortality, medication errors, falls, pressure ulcers, and patient satisfaction
      with nurses. Use of SRNs ranged from 0% to 30.4% of total RN hours per unit
      quarter. Among 188 of the 304 unit quarters in which SRNs were used, the average
      SRN use was 9.8% in non-ICUs and 6.4% in ICUs. All observed effects of SRN use on
      patient outcomes were nonsignificant. Use of SRNs was substantial and varied
      widely by unit. No evidence was found that links SRN use to either adverse or
      positive patient outcomes.

PMID- 23151933
TI  - Explaining patient satisfaction with outpatient care using data-based nurse
      staffing indicators.
AB  - OBJECTIVE: This article examines the associations of nursing intensity, work
      environment intensity, and nursing resources with patient satisfaction with
      outpatient care in a university hospital in Finland. BACKGROUND: While readily
      available in hospital information systems, data-based nurse staffing indicators
      have not been maximized in ambulatory nursing management and leadership. METHODS:
      Data were analyzed using descriptive and multivariate statistical methods.
      RESULTS: Patient satisfaction scores reached target levels at all measurements in
      42% of the outpatient departments. The risk of low satisfaction scores was higher
      when patients received no information about their visits or their illness.
      Patient dissatisfaction increased linearly with the number of repeat visits.
      CONCLUSIONS: The patients were predominantly satisfied with the outpatient care.
      Better access to information improved patient satisfaction. Attention should be
      directed to the content of information in patient repeat visits.

PMID- 23151934
TI  - [Neurological deficits and ipsilateral skin lesions of the face].
AB  - A 68-year-old woman presented with unilateral herpetiform skin lesions of the
      face. She also showed reduced eye lid and mimic function as well as hearing loss.
      In addition grouped vesicles were seen in the outer ear canal. We diagnosed
      Ramsay Hunt syndrome and administered intravenous acyclovir, prednisolone and
      pentoxifylline. Within a few weeks, there was complete remission including the
      neurological symptoms.

PMID- 23151935
TI  - Defective DNA repair systems and the development of breast and prostate cancer
      (review).
AB  - Genetic defects in DNA repair and DNA damage response genes often lead to an
      increase in cancer incidence. The role of defects is also associated with the
      modulation of hormone signaling pathways. A number of studies have suggested a
      role for estrogen in the regulation of DNA repair activity. Furthermore,
      mutations or epigenetic silencing in DNA repair genes have been associated with
      the sensitivity of cancers to hormonal therapy. The molecular basis for the
      progression of cancers from hormone-dependent to hormone-independent remains a
      critical issue in the management of these types of cancer. In the present review,
      we aimed to summarize the function of DNA repair molecules from the viewpoint of
      carcinogenesis and hormone-related cell modulation, providing a comprehensive
      view of the molecular mechanisms by which hormones may exert their effects on the
      regulation of tumor progression.

PMID- 23151936
TI  - Nanostructured carbon-metal oxide composite electrodes for supercapacitors: a
      review.
AB  - This paper presents a review of the research progress in the carbon-metal oxide
      composites for supercapacitor electrodes. In the past decade, various carbon
      metal oxide composite electrodes have been developed by integrating metal oxides
      into different carbon nanostructures including zero-dimensional carbon
      nanoparticles, one-dimensional nanostructures (carbon nanotubes and carbon
      nanofibers), two-dimensional nanosheets (graphene and reduced graphene oxides) as
      well as three-dimensional porous carbon nano-architectures. This paper has
      described the constituent, the structure and the properties of the carbon-metal
      oxide composites. An emphasis is placed on the synergistic effects of the
      composite on the performance of supercapacitors in terms of specific capacitance,
      energy density, power density, rate capability and cyclic stability. This paper
      has also discussed the physico-chemical processes such as charge transport, ion
      diffusion and redox reactions involved in supercapacitors.

PMID- 23151937
TI  - Radiographic assessment of age from epiphyseal fusion at knee joint.

PMID- 23151938
TI  - Response to commentary on "radiographic analysis of epiphyseal fusion at knee
      joint to assess likelihood of having attained 18 years of age".

PMID- 23151939
TI  - Characterizing long-term land use/cover change in the United States from 1850 to
      2000 using a nonlinear bi-analytical model.
AB  - We relate the historical (1850-2000) spatial and temporal changes in cropland
      cover in the conterminous United States to several socio-economic and biophysical
      determinants using an eco-region based spatial framework. Results show population
      density as a major determinant during the nineteenth century, and biophysical
      suitability as the major determinant during the twentieth century. We further
      examine the role of technological innovations, socio-economic and socio
      ecological feedbacks that have either sustained or altered the cropland
      trajectories in different eco-regions. The cropland trajectories for each of the
      84 level-III eco-regions were analyzed using a nonlinear bi-analytical model. In
      the Eastern United States, low biophysically suitable eco-regions, e.g., New
      England, have shown continual decline in the cropland after reaching peak levels.
      The cropland trajectories in high biophysically suitable regions, e.g., Corn
      Belt, have stabilized after reaching peak levels. In the Western United States,
      low-intensity crop cover (<10 %) is sustained with irrigation support. A slower
      rate of land conversion was found in the industrial period. Significant effect of
      Conservation Reserve Program on planted crop area is found in last two decades
      (1990-2010).

PMID- 23151940
TI  - Pharmacokinetic interaction between methotrexate and chloral hydrate.
AB  - We report the case of a drug interaction between methotrexate (MTX) and chloral
      hydrate (CH) observed in a child treated for acute leukemia. Significantly slower
      MTX clearance and increased MTX exposure occurred on the first three courses of a
      high-dose chemotherapy when co-administered with CH despite normal renal
      function, adequate hydration, and alkalinization. Mean MTX area under the curve
      associated with CH administration was 1,134 umol hours/L, compared to 608 umol
      hours/L after discontinuation of CH. This interaction possibly resulted from a
      competition between anionic CH metabolites and MTX for renal tubular excretion.

PMID- 23151941
TI  - Evaluation of cervical stiffness during pregnancy using semiquantitative
      ultrasound elastography.
AB  - OBJECTIVE: To evaluate cervical stiffness during pregnancy using ultrasound
      derived elastography, a method used to estimate the average tissue displacement
      (strain) within a defined region of interest when oscillatory compression is
      applied. METHODS: Strain was calculated in two regions of interest, the
      endocervical canal and the entire cervix, from three anatomical planes of the
      cervix: mid-sagittal in the plane used for cervical length measurement and in
      cross-sectional planes located at the internal and external cervical os.
      Associations between strain values, method of ascertainment and patient
      characteristics were assessed using linear mixed models to account for within
      subject correlation. Inter-rater agreement in defining the degree of cervical
      stiffness was evaluated in 120 regions of interest acquired by two operators in
      20 patients. RESULTS: A total of 1557 strain estimations were performed in 262
      patients at 8-40 weeks of gestation. Adjusting for other sources of variation,
      (1) cervical tissue strain estimates obtained in the endocervical canal were on
      average 33% greater than those obtained in the entire cervix; (2) measurements
      obtained in the cross-sectional plane of the external cervical os and sagittal
      plane were 45% and 13% greater than those measured in the cross-sectional plane
      of the internal cervical os, respectively; (3) mean strain rates were 14% and 5%
      greater among parous women with and without a history of preterm delivery
      compared with those of nulliparous women, respectively, and were on average 13%
      greater among women with a cervical length of between 25 and 30 mm compared to
      those with a cervical length of > 30 mm; and (4) cervical tissue strain was more
      strongly associated with cervical length than with gestational age. CONCLUSION:
      Semiquantitative elastography can be employed to evaluate changes in cervical
      stiffness during pregnancy.

PMID- 23151942
TI  - Primmorphs cryopreservation: a new method for long-time storage of sponge cells.
AB  - The possibility to cryopreserve cells allows for wide opportunities of flexible
      handling of cell cultures from different sponge species. Primmorphs model, a
      multicellular 3D aggregate formed by dissociated sponge cells, is considered one
      of the best approaches to establish sponge cell culture but, in spite of the
      available protocols for freezing sponge cells, there is no information regarding
      the ability of the latter to form primmorphs after thawing. In the present work,
      we demonstrate that, after a freezing and thawing cycle using dissociated
      Petrosia ficiformis cells as a model, cells viability was high but it was not
      possible to obtain primmorphs. The same protocol for cryopreservation was then
      used to directly freeze primmorphs. In this second case, after thawing, viability
      and the cellular proliferative level were similar to unfrozen standard
      primmorphs. Spiculogenesis in thawed primmorphs was evaluated by quantifying the
      silicatein gene expression level and by assaying the silica amount in the newly
      formed spicules, then compared with the correspondent values obtained in standard
      unfrozen primmorphs. Results indicate that the freezing cycle does not affect the
      spiculogenesis rate. Finally, the expression level of heat shock protein 70, a
      well-known stress marker, was assayed and the results showed no differences
      between frozen and unfrozen samples. These findings are likely to promote
      relevant improvements in sponge cell culture technique, allowing for a worldwide
      exchange of living biological material, paving the way for cell banking of
      Porifera.

PMID- 23151943
TI  - Analysis of soluble protein contents from the nematocysts of a model sea anemone
      sheds light on venom evolution.
AB  - The nematocyst is one of the most complex intracellular structures found in
      nature and is the defining feature of the phylum Cnidaria (sea anemones, corals,
      jellyfish, and hydroids). This miniature stinging organelle contains and delivers
      venom into prey and foe yet little is known about its toxic components. In the
      present study, we identified by tandem mass spectrometry 20 proteins released
      upon discharge from the nematocyst of the model sea anemone Nematostella
      vectensis. The availability of genomic and transcriptomic data for this species
      enabled accurate identification and phylogenetic study of these components.
      Fourteen of these proteins could not be identified in other animals suggesting
      that they might be the products of taxonomically restricted genes, a finding
      which fits well their origin from a taxon-specific organelle. Further, we studied
      by in situ hybridization the localization of two of the transcripts encoding the
      putative nematocyst venom proteins: a metallopeptidase related to the Tolloid
      family and a cysteine-rich protein. Both transcripts were detected in
      nematocytes, which are the cells containing nematocysts, and the metallopeptidase
      was found also in pharyngeal gland cells. Our findings reveal for the first time
      the possible venom components of a sea anemone nematocyst and suggest their
      evolutionary origins.

PMID- 23151944
TI  - Zoledronic acid-induced expansion of gammadelta T cells from early-stage breast
      cancer patients: effect of IL-18 on helper NK cells.
AB  - Human gammadelta T cells display potent cytotoxicity against various tumor cells
      pretreated with zoledronic acid (Zol). Zol has shown benefits when added to
      adjuvant endocrine therapy for patients with early-stage breast cancer or to
      standard chemotherapy for patients with multiple myeloma. Although gammadelta T
      cells may contribute to this additive effect, the responsiveness of gammadelta T
      cells from early-stage breast cancer patients has not been fully investigated. In
      this study, we determined the number, frequency, and responsiveness of
      Vgamma2Vdelta2 T cells from early- and late-stage breast cancer patients and
      examined the effect of IL-18 on their ex vivo expansion. The responsiveness of
      Vgamma2Vdelta2 T cells from patients with low frequencies of Vgamma2Vdelta2 T
      cells was significantly diminished. IL-18, however, enhanced ex vivo
      proliferative responses of Vgamma2Vdelta2 T cells and helper NK cells from
      patients with either low or high frequencies of Vgamma2Vdelta2 T cells. Treatment
      of breast cancer patients with Zol alone decreased the number of Vgamma2Vdelta2 T
      cells and reduced their ex vivo responsiveness. These results demonstrate that
      Zol can elicit immunological responses by gammadelta T cells from early-stage
      breast cancer patients, but that frequent in vivo treatment reduces
      Vgamma2Vdelta2 T cell numbers and their responsiveness to stimulation.

PMID- 23151945
TI  - Enhancement of the anti-melanoma response of Hu14.18K322A by alphaCD40 + CpG.
AB  - Targeted monoclonal antibodies (mAb) can be used therapeutically for tumors with
      identifiable antigens such as disialoganglioside GD2, expressed on neuroblastoma
      and melanoma tumors. Anti-GD2 mAbs (alphaGD2) can provide clinical benefit in
      patients with neuroblastoma. An important mechanism of mAb therapy is antibody
      dependent cellular cytotoxicity (ADCC). Combinatorial therapeutic strategies can
      dramatically increase the anti-tumor response elicited by mAbs. We combined a
      novel alphaGD2 mAb, hu14.18K322A, with an immunostimulatory regimen of agonist
      CD40 mAb and class B CpG-ODN 1826 (CpG). Combination immunotherapy was more
      effective than the single therapeutic components in a syngeneic model of GD2
      expressing B16 melanoma with minimal tumor burden. NK cell depletion in B6 mice
      showed that NK cells were required for the anti-tumor effect; however, anti-tumor
      responses were also observed in tumor-bearing SCID/beige mice. Thus, NK cell
      cytotoxicity did not appear to be essential. Peritoneal macrophages from anti
      CD40 + CpG-treated mice inhibited tumor cells in vitro in an hu14.18K322A
      antibody-dependent manner. These data highlight the importance of myeloid cells
      as potential effectors in immunotherapy regimens utilizing tumor-specific mAb and
      suggest that further studies are needed to investigate the therapeutic potential
      of activated myeloid cells and their interaction with NK cells.

PMID- 23151947
TI  - Lysine-directed staining of proteins for MS-based analyses.
AB  - Visualization of proteins and MS-based analyses are elemental tasks in modern
      biochemistry. Nevertheless, reports about covalent protein dyes and their
      suitability for subsequent MS experiments remain scarce. In a recent work, we
      demonstrated that covalent prestaining of proteins with Uniblue A drastically
      speeds up proteomic workflows. The present study introduces dabsyl chloride as
      another truly MS-compatible protein stain. Remarkably, although Uniblue A and
      dabsyl chloride employ different nucleophilic reaction mechanisms, both are
      highly specific for lysine residues. The predictable peptide modifications allow
      easy integration into state-of-the-art bioinformatic workflows. Further, lysine
      directed derivatizations with hydrophobic reagents such as dabsyl chloride
      complement the cysteine-directed ALiPHAT strategy for increasing the sensitivity
      of peptide identifications.

PMID- 23151946
TI  - Guanosine protects against reperfusion injury in rat brains after ischemic
      stroke.
AB  - After ischemic stroke, early thrombolytic therapy to reestablish tissue perfusion
      improves outcome but triggers a cascade of deleterious cellular and molecular
      events. Using a collaborative approach, our groups examined the effects of
      guanosine (Guo) in response to ischemic reperfusion injury in vitro and in vivo.
      In a transient middle cerebral artery occlusion (MCAO) in rats, Guo significantly
      reduced infarct volume in a dose-dependent manner when given systemically either
      immediately before or 30 min, but not 60 min, after the onset of the 5.5-hr
      reperfusion period. In a separate experiment, Guo significantly reduced infarct
      volume after 24 hr of reperfusion when administered 5 min before reperfusion.
      Western blot analysis did not reveal any significant changes either in
      endoplasmic reticulum (ER) stress proteins (GRP 78 and 94) or HSP 70 or in levels
      of m-calpain. In vitro oxygen and glucose deprivation (OGD) significantly
      increased production of both reactive oxygen species (ROS) and interleukin-8 (IL
      8) in the primary astrocytes. Guo did not alter ROS or IL-8 production when given
      to the astrocytes before OGD. However, Guo when added to the cells prior to or 30
      min after reperfusion significantly reduced IL-8 release but not ROS formation.
      Our study revealed a dose- and time-dependent protective effect of Guo on
      reperfusion injury in vitro and vivo. The mechanisms by which Guo exerts its
      effect are independent of unfolded proteins in ER or the level of intracellular
      calcium or ROS formation. However, the effect may be induced, at least partially,
      by inhibiting IL-8, a marker of reperfusion-triggered proinflammatory events.

PMID- 23151948
TI  - Activation of the human immune system via toll-like receptors by the oncolytic
      parvovirus H-1.
AB  - This study aimed to investigate the function of toll-like receptors (TLRs) during
      oncolytic parvovirus H-1 (H-1PV)-induced human immune responses. First, the role
      of TLRs in the activation of the NFkappaB transcription factor was characterized;
      second, the immunologic effects of H-1PV-induced tumor cell lysates (TCL) on
      human antitumor immune responses were evaluated. A human ex vivo model was used
      to study immune responses with dendritic cells (DCs). Human embryonic kidney
      cells (HEK293) transfected to stably express TLRs were used as potential human DC
      equivalents to further investigate the role of specific TLRs during immune
      activation. TLR3 and TLR9 were activated by H-1PV infection, which correlated
      with NFkappaB translocation to the nucleus and a reduced cytoplasmic IkappaB
      expression. Using a TLR-signaling reporter plasmid (pNiFty-Luc), NFkappaB
      activity was increased following H-1PV infection. In addition, human DCs
      coincubated with H-1PV-induced TCL demonstrated increased TLR3 and TLR9
      expression. These data suggest that H-1PV-induced TCL stimulate human DCs at
      least in part through TLR-dependent signaling pathways. Thus, DC maturation
      occurred through exposure to H-1PV-induced TCL through TLR-signaling leading to
      NFkappaB-dependent activation of the adaptive immune system as indicated by the
      increased expression of CD86, TLR3 and TLR9. Furthermore, the transcription of
      various cytokines indicates the activation of immune response, therefore the
      production of the proinflammatory cytokine TNF-alpha was determined. Here, H-1PV
      induced TCL significantly enhanced the TNF-alpha level by DCs after coculture. H
      1PV oncolytic virotherapy enhances immune priming by different effects on DCs and
      generates antitumor immunity. These findings potentially offer a new approach to
      tumor therapy.

PMID- 23151949
TI  - Epilepsy in adults and access to care--United States, 2010.
AB  - Epilepsy is a neurologic disorder that negatively affects the quality of life for
      millions of persons in the United States; however, nationally representative U.S.
      estimates of the prevalence of epilepsy are scant. To determine epilepsy
      prevalence among adults, assess their access to care, and provide baseline
      estimates for a Healthy People 2020 objective ("Increase the proportion of
      persons with epilepsy and uncontrolled seizures who receive appropriate medical
      care"), CDC analyzed data from the 2010 National Health Interview Survey (NHIS).
      The results of that analysis indicated that, in 2010, an estimated 1.0% of U.S.
      adults and 1.9% of those with annual family income levels <=$34,999 had active
      epilepsy. In addition, only 52.8% of adults with active epilepsy reported seeing
      a neurologic specialist in the preceding 12 months. Public health agencies can
      work with Epilepsy Foundation state affiliates and other health and human service
      providers to eliminate identified barriers to care for persons with epilepsy.

PMID- 23151950
TI  - Comprehensive smoke-free laws--50 largest U.S. cities, 2000 and 2012.
AB  - Secondhand smoke (SHS) exposure causes heart disease and lung cancer in
      nonsmoking adults and several health conditions in children. Only completely
      eliminating smoking in indoor spaces fully protects nonsmokers from SHS. State
      and local laws can provide this protection in enclosed workplaces and public
      places by completely eliminating smoking in these settings. CDC considers a smoke
      free law to be comprehensive if it prohibits smoking in all indoor areas of
      private workplaces, restaurants, and bars, with no exceptions. In response to
      growing evidence on the health effects of SHS, communities and states have
      increasingly adopted comprehensive smoke-free (CSF) laws in recent years. To
      assess trends in protecting the population from SHS exposure, CDC and the
      American Nonsmokers' Rights Foundation (ANRF) compared coverage by local or state
      CSF laws in the 50 largest U.S. cities as of December 31, 2000, and October 5,
      2012. The analysis focused on smoking restrictions in the 50 largest cities
      because these cities represent an important indicator of nationwide trends in
      local and state policy and because they are home to an estimated 47 million
      persons, or nearly 15% of the U.S. population. The analysis found that the number
      of these cities covered by local and/or state CSF laws increased from one city
      (2%) in 2000 to 30 cities (60%) in 2012. A total of 20 cities (40%) were not
      covered by a CSF law at either the local or state level in 2012, although 14 of
      these cities had 100% smoke-free provisions in place at the local or state level
      in at least one of the three settings considered. The results of this analysis
      indicate that substantial progress has been achieved during 2000-2012 in
      implementing CSF laws in the 50 largest U.S. cities. However, gaps in coverage,
      especially in the southern United States and in states with laws that preempt
      local smoking restrictions, are contributing to disparities in SHS protections.

PMID- 23151951
TI  - Increasing prevalence of diagnosed diabetes--United States and Puerto Rico, 1995
      2010.
AB  - In 2010, an estimated 18.8 million persons in the United States had diagnosed
      diabetes mellitus and another 7.0 million had undiagnosed diabetes. Since 1990,
      the prevalence of diagnosed diabetes in the United States has risen sharply among
      all age groups, both sexes, and all racial/ethnic groups for which data are
      available. To learn whether the increase has been greater in some regions of the
      United States than in others, data on self-reported diabetes in adults collected
      during 1995-2010 by the Behavioral Risk Factor Surveillance System (BRFSS) were
      analyzed. The analysis showed that the age-adjusted prevalence of diagnosed
      diabetes increased during the interval in every state, the District of Columbia
      (DC), and Puerto Rico. In 1995, age-adjusted prevalence was >=6% in only three
      states, DC, and Puerto Rico, but by 2010 it was >=6% in every state, DC, and
      Puerto Rico, and >=10.0% in six states and Puerto Rico. Strategies to prevent
      diabetes and its preventable risk factors are needed, especially for those at
      highest risk for diabetes, to slow the rise in diabetes prevalence across the
      United States. Continued surveillance of diabetes prevalence and incidence, its
      risk factors, and prevention efforts is important to measure progress of
      prevention efforts.

PMID- 23151952
TI  - Vital signs: racial disparities in breast cancer severity--United States, 2005
      2009.
AB  - BACKGROUND: Breast cancer death rates have been declining among U.S. women since
      1990 because of early detection and advances in treatment; however, all racial
      groups have not benefited equally. METHODS: Breast cancer incidence, stage at
      diagnosis, and mortality rates for 2005-2009 for women in the United States and
      for each state were calculated using United States Cancer Statistics (USCS) data.
      Black to white mortality ratios and mortality to incidence ratios by race were
      calculated. RESULTS: Despite having lower incidence rates, black women had a 41%
      higher breast cancer death rate. More black women were diagnosed at regional or
      distant cancer stage compared with white women (45% versus 35%). For every 100
      breast cancers diagnosed, black women had nine more deaths than white women (27
      deaths per 100 breast cancers diagnosed among black women compared with 18 per
      100 among white women). CONCLUSIONS: Despite significant progress in breast
      cancer detection and treatment, black women experience higher death rates even
      though they have a lower incidence of breast cancer compared to white women.
      IMPLICATIONS FOR PUBLIC HEALTH PRACTICE: Advances in screening and treatment have
      improved survival for U.S. women with breast cancer. However, black women
      experience inequities in breast cancer screening, follow-up, and treatment after
      diagnosis, leading to greater mortality. At the individual level, the maximal
      effectiveness of screening for breast cancer can only be achieved when all women
      have timely follow-up to breast cancer exams and state-of-the-art treatment. At
      the health system level, optimal health-care delivery may be strengthened through
      performance-based reimbursement, expanded use of information technology, and
      quality assurance reporting-protocols. Proven effective interventions such as
      patient navigation could be expanded for use in other settings.

PMID- 23151954
TI  - Hantavirus infection: an emerging infectious disease causing acute renal failure.
AB  - The function of the kidney with its highly differentiated and specialized cell
      types is affected by infection with several viruses. Viral infections of the
      kidney have a negative impact not only on patients undergoing renal
      transplantation and immunosuppression. Besides the increasing number of patients
      suffering from HIV-associated nephropathy, another group of viruses infects
      immunocompetent patients and induces renal failure. Hantaviruses belong nowadays
      to the emerging zoonoses that increase in number and geographic distribution. The
      viruses are distributed worldwide in endemic areas and distribution seems to
      expand. Together with the increase in the number of cases in the last few years,
      the understanding of epidemiology and pathology has deepened and some concepts
      had to be changed. Symptoms and mortality vary between species. The
      classification refers to geographical distribution: New World hantaviruses
      causing hantavirus cardiopulmonary syndrome (HCPS) and Old World hantaviruses
      causing hemorrhagic fever with renal syndrome (HFRS). Indeed, in most HFRS cases,
      the kidney is mainly affected and HCPS is characterized by cardiopulmonary
      involvement. But the picture of strict organ tropism is changing and reports of
      pulmonary findings and nonrenal manifestations in infections with Old World
      hantaviruses are increasing. However, the overall symptoms-vascular alterations
      and leakage-that are responsible for organ failure are characteristic for all
      diseases caused by hantaviruses.

PMID- 23151955
TI  - Logical circularity in voxel-based analysis: normalization strategy may induce
      statistical bias.
AB  - Recent discussions within the neuroimaging community have highlighted the
      problematic presence of selection bias in experimental design. Although initially
      centering on the selection of voxels during the course of fMRI studies, we
      demonstrate how this bias can potentially corrupt voxel-based analyses. For such
      studies, template-based registration plays a critical role in which a
      representative template serves as the normalized space for group alignment. A
      standard approach maps each subject's image to a representative template before
      performing statistical comparisons between different groups. We analytically
      demonstrate that in these scenarios the popular sum of squared difference (SSD)
      intensity metric, implicitly surrogating as a quantification of anatomical
      alignment, instead explicitly maximizes effect size--an experimental design flaw
      referred to as "circularity bias." We illustrate how this selection bias varies
      in strength with the similarity metric used during registration under the
      hypothesis that while SSD-related metrics, such as Demons, will manifest similar
      effects, other metrics which are not formulated based on absolute intensity
      differences will produce less of an effect. Consequently, given the variability
      in voxel-based analysis outcomes with similarity metric choice, we caution
      researchers specifically in the use of SSD and SSD-related measures where
      normalization and statistical analysis involve the same image set. Instead, we
      advocate a more cautious approach where normalization of the individual subject
      images to the reference space occurs through corresponding image sets which are
      independent of statistical testing. Alternatively, one can use similarity terms
      that are less sensitive to this bias.

PMID- 23151956
TI  - A systematic overview of harvesting-induced maturation evolution in predator-prey
      systems with three different life-history tradeoffs.
AB  - There are concerns that anthropogenic harvesting may cause phenotypic adaptive
      changes in exploited wild populations, in particular maturation at a smaller size
      and younger age. In this paper, we study the evolutionarily stable size at
      maturation of prey subjected to size-selective harvesting in a simple predator
      prey model, taking into account three recognized life-history costs of early
      maturation, namely reduced fecundity, reduced growth, and increased mortality.
      Our analysis shows that harvesting large individuals favors maturation at smaller
      size compared to the unharvested system, independent of life-history tradeoff and
      the predator's prey-size preference. In general, however, the evolutionarily
      stable maturation size can either increase or decrease relative to the
      unharvested system, depending on the harvesting regime, the life-history
      tradeoff, and the predator's preferred size of prey. Furthermore, we examine how
      the predator population size changes in response to adaptive change in size at
      maturation of the prey. Surprisingly, in some situations, we find that the
      evolutionarily stable maturation size under harvesting is associated with an
      increased predator population size. This occurs, in particular, when early
      maturation trades off with growth rate. In total, we determine the evolutionarily
      stable size at maturation and associated predator population size for a total of
      forty-five different combinations of tradeoff, harvest regime, and predated size
      class.

PMID- 23151953
TI  - Percutaneous revascularization for ischemic nephropathy: the past, present, and
      future.
AB  - Occlusion of the renal arteries can threaten the viability of the kidney when
      severe, in addition to accelerating hypertension and circulatory congestion.
      Renal artery stenting procedures have evolved from a treatment mainly for
      renovascular hypertension to a maneuver capable of recovering threatened renal
      function in patients with 'ischemic nephropathy' and improving management of
      congestive heart failure. Improved catheter design and techniques have reduced,
      but not eliminated, hazards associated with renovascular stenting. Expanded use
      of endovascular stent grafts to treat abdominal aortic aneurysms has introduced a
      new indication for renal artery stenting to protect the renal circulation when
      grafts cross the origins of the renal arteries. Although controversial,
      prospective randomized trials to evaluate the added benefit of revascularization
      to current medical therapy for atherosclerotic renal artery stenosis until now
      have failed to identify major benefits regarding either renal function or blood
      pressure control. These studies have been limited by selection bias and have been
      harshly criticized. While studies of tissue oxygenation using blood-oxygen-level
      dependent (BOLD) magnetic resonance establish that kidneys can adapt to reduced
      blood flow to some degree, more severe occlusive disease leads to cortical
      hypoxia associated with microvascular rarefaction inflammatory injury, and
      fibrosis. Current research is directed toward identifying pathways of
      irreversible kidney injury due to vascular occlusion and to increase the
      potential for renal repair after restoring renal artery patency. The role of
      nephrologists likely will focus upon recognizing the limits of renal adaptation
      to vascular disease and identifying kidneys truly at risk for ischemic injury at
      a time point when renal revascularization can still be of benefit to recovering
      kidney function.

PMID- 23151958
TI  - An exactly solvable model of random site-specific recombinations.
AB  - Cre-lox and other systems are used as genetic tools to control site-specific
      recombination (SSR) events in genomic DNA. If multiple recombination sites are
      organized in a compact cluster within the same genome, a series of random
      recombination events may generate substantial cell specific genomic diversity.
      This diversity is used, for example, to distinguish neurons in the brain of the
      same multicellular mosaic organism, within the brainbow approach to neuronal
      connectome. In this paper, we study an exactly solvable statistical model for SSR
      operating on a cluster of recombination sites. We consider two types of
      recombination events: inversions and excisions. Both of these events are
      available in the Cre-lox system. We derive three properties of the sequences
      generated by multiple recombination events. First, we describe the set of
      sequences that can in principle be generated by multiple inversions operating on
      the given initial sequence. We call this description the ergodicity theorem. On
      the basis of this description, we calculate the number of sequences that can be
      generated from an initial sequence. This number of sequences is experimentally
      testable. Second, we demonstrate that after a large number of random inversions
      every sequence that can be generated is generated with equal probability. Lastly,
      we derive the equations for the probability to find a sequence as a function of
      time in the limit when excisions are much less frequent than inversions, such as
      in shufflon sequences.

PMID- 23151959
TI  - Haptic distal spatial perception mediated by strings: size at a distance and
      egocentric localization based on ellipse geometry.
AB  - Participants explored ellipse perimeters defined by fixed-length strings, held
      taut by their moving finger, with ends attached to two fixed hooks (foci).
      Participants haptically judged ellipse interfocal distance (IFD; in effect,
      exocentric separation, or size at a distance) or location of ellipse major axes
      (i.e., egocentric localization relative to the moving finger). In Experiment 1A,
      perceivers made reliable and accurate multialternative forced choice IFD
      judgments. Experiment 1B showed similar reliability for direct estimations but
      showed greater scaling error. In Experiment 2, perceivers reliably localized
      ellipse major axes. Both experiments derived from a priori geometrical analysis,
      consistent with the Gibsonian perceptual research program and previous string
      mediated haptic distal spatial studies. Results are discussed with respect to
      haptic perception as a telemodality and to dynamic touch.

PMID- 23151957
TI  - Hypoxic cell waves around necrotic cores in glioblastoma: a biomathematical model
      and its therapeutic implications.
AB  - Glioblastoma is a rapidly evolving high-grade astrocytoma that is distinguished
      pathologically from lower grade gliomas by the presence of necrosis and
      microvascular hyperplasia. Necrotic areas are typically surrounded by
      hypercellular regions known as "pseudopalisades" originated by local tumor vessel
      occlusions that induce collective cellular migration events. This leads to the
      formation of waves of tumor cells actively migrating away from central hypoxia.
      We present a mathematical model that incorporates the interplay among two tumor
      cell phenotypes, a necrotic core and the oxygen distribution. Our simulations
      reveal the formation of a traveling wave of tumor cells that reproduces the
      observed histologic patterns of pseudopalisades. Additional simulations of the
      model equations show that preventing the collapse of tumor microvessels leads to
      slower glioma invasion, a fact that might be exploited for therapeutic purposes.

PMID- 23151960
TI  - Temporal characteristics of overt attentional behavior during category learning.
AB  - Many theories of category learning incorporate mechanisms for selective
      attention, typically implemented as attention weights that change on a trial-by
      trial basis. This is because there is relatively little data on within-trial
      changes in attention. We used eye tracking and mouse tracking as fine-grained
      measures of attention in three complex visual categorization tasks to investigate
      temporal patterns in overt attentional behavior within individual categorization
      decisions. In Experiments 1 and 2, we recorded participants' eye movements while
      they performed three different categorization tasks. We extended previous
      research by demonstrating that not only are participants less likely to fixate
      irrelevant features, but also, when they do, these fixations are shorter than
      fixations to relevant features. We also found that participants' fixation
      patterns show increasingly consistent temporal patterns. Participants were
      faster, although no more accurate, when their fixation sequences followed a
      consistent temporal structure. In Experiment 3, we replicated these findings in a
      task where participants used mouse movements to uncover features. Overall, we
      showed that there are important temporal regularities in information sampling
      during category learning that cannot be accounted for by existing models. These
      can be used to supplement extant models for richer predictions of how information
      is attended to during the buildup to a categorization decision.

PMID- 23151961
TI  - Using response time distributions to examine top-down influences on attentional
      capture.
AB  - Three experiments examined contingent attentional capture, which is the finding
      that cuing effects are larger when cues are perceptually similar to a target than
      when they are dissimilar to the target. This study also analyzed response times
      (RTs) in terms of the underlying distributions for valid cues and invalid cues.
      Specifically, an ex-Gaussian analysis and a vincentile analysis examined the
      influence of top-down attentional control settings on the shift and skew of RT
      distributions and how the shift and the skew contributed to the cuing effects in
      the mean RTs. The results showed that cue/target similarity influenced the size
      of cuing effects. The RT distribution analyses showed that the cuing effects
      reflected only a shifting effect, not a skewing effect, in the RT distribution
      between valid cues and invalid cues. That is, top-down attentional control
      moderated the cuing effects in the mean RTs through distribution shifting, not
      distribution skewing. The results support the contingent orienting hypothesis
      (Folk, Remington, & Johnston, Journal of Experimental Psychology: Human
      Perception and Performance, 18, 1030-1044, 1992) over the attentional
      disengagement account (Theeuwes, Atchley, & Kramer, 2000) as an explanation for
      when top-down attentional settings influence the selection of salient stimuli.

PMID- 23151962
TI  - The perceived onset position of a moving target: effects of trial contexts are
      evoked by different attentional allocations.
AB  - Previous studies have shown that the localization of the perceived onset position
      of a moving target varies with the trial context. When the moving target appeared
      at predictable positions to the left or right of fixation (constant context),
      localization judgments of the perceived onset positions were essentially
      displaced in motion direction (Frohlich effect). In contrast, when the target
      appeared at unpredictable positions in the visual field (random context),
      localization judgments were at least drastically reduced. Four explanations of
      this influence of trial context on localization judgments were examined in three
      experiments. Findings ruled out an overcompensation mechanism effective in random
      context conditions, a predictive mechanism effective in constant-context
      conditions and a detrimental mechanism originating from more trial repetitions in
      constant-context conditions. Instead, the results indicated that different
      attentional allocations are responsible for the localization differences. They
      also demonstrated that attentional mechanisms are at the basis of the Frohlich
      effect.

PMID- 23151963
TI  - Household composition and suicidal behaviour in the adult population of Belgium.
AB  - PURPOSE: We aimed to estimate the prevalence of suicidal behaviours, i.e.
      ideation and attempt, in the adult population of Belgium, and to explore their
      association with household composition. METHODS: Data of 4,459 adults (25-64
      years) from the 2004 Belgian Health Interview Survey were used for analyses.
      Bivariate and multivariate logistic regressions were used to calculate the odds
      of engaging in suicidal behaviours according to household type, further
      controlling for age, sex, income, employment status and social support. RESULTS:
      Lifetime prevalence of ideation and attempts was 14 and 4.7 %, respectively.
      Current prevalence of ideation was 4.0 % and past year prevalence of attempts was
      0.5 %. Compared to other household compositions, living alone (A) and as lone
      parent (P) increased the odds of lifetime and current suicidal thoughts (ORA 2.3,
      95 % CI 1.7-2.9 and ORP 3.8, 95 % CI 1.9-7.7) and lifetime attempts (ORA 2.3, 95
      % CI 1.4-3.6 and ORP 4.5, 95 % CI 2.4-8.5). When controlling for confounders,
      single person and single parent households still presented increased adjusted
      odds of lifetime and current suicidal thoughts (a-ORA 1.8, 95 % CI 1.1-2.9 and a
      ORP 2.3, 95 % CI 1.0-5.5). The likelihood of ever attempted suicide was also
      higher among single parent households (a-ORP 4.5, 95 % CI 2.4-8.5) after
      adjustment, but not among those living alone (a-ORA 1.4, 95 % CI 0.8-2.8).
      CONCLUSION: Living alone or as lone parent place adults at higher risk for
      suicide behaviour, and this is only partly explained by lower socio-economic
      status or poor perceived support.

PMID- 23151964
TI  - Depuration of tetrodotoxin and changes in bacterial communities in Pleurobranchea
      maculata adults and egg masses maintained in captivity.
AB  - Depuration of tetrodotoxin (TTX) was investigated in adult grey side-gilled sea
      slugs, Pleurobranchaea maculata, maintained in captivity on a TTX-free diet.
      Three adults were harvested every 21 days for 126 days, and TTX concentrations
      were measured in organs/tissues and egg masses. Automated rRNA intergenic spacer
      analysis (ARISA) was used to investigate bacterial community structure in
      selected samples. Linear modeling of adult data demonstrated a decline (P<0.001)
      in average total TTX concentrations over time. Temporal data obtained from a wild
      population showed similar depuration rates, indicating that once adults reach a
      certain size, or sexual maturity, TTX is no longer produced or acquired
      substantially. Depuration rates differed among organs, with concentrations in the
      heart declining the fastest. The gonads had the slowest and least significant
      depuration rate indicating, at most, weak depuration of this tissue. There was a
      strong correlation (R(2)=0.66) between TTX concentrations in the first-laid egg
      masses and total TTX in the corresponding adult. These data suggest that adult P.
      maculata transfer TTX to their offspring, and presumably that functions as a
      chemical defense. ARISA data showed a shift in bacterial community structure
      within 3 weeks of introduction to captivity. Based on the combined data, the
      exact origin of TTX in P. maculata is unclear, with evidence both in favor and
      against a dietary source, and endogenous or bacterial production.

PMID- 23151965
TI  - Spin-dependent thermoelectric effects in graphene-based spin valves.
AB  - Using first-principles calculations combined with non-equilibrium Green's
      function (NEGF), we investigate spin-dependent thermoelectric effects in a spin
      valve which consists of zigzag graphene nanoribbon (ZGNR) electrodes with
      different magnetic configurations. We find that electron transport properties in
      the ZGNR-based spin valve are strongly dependent on the magnetic configurations.
      As a result, with a temperature bias, thermally-induced currents can be
      controlled by switching the magnetic configurations, indicating a thermal
      magnetoresistance (MR) effect. Moreover, based on the linear response assumption,
      our study shows that the remarkably different Seebeck coefficients in the various
      magnetic configurations lead to a very large and controllable magneto Seebeck
      ratio. In addition, we evaluate thermoelectric properties, such as the power
      factor, electron thermal conductance and figure of merit (ZT), of the ZGNR-based
      spin valve. Our results indicate that the power factor and the electron thermal
      conductance are strongly related to the transmission gap and electron-hole
      symmetry of the transmission spectrum. Moreover, the value of ZT can reach 0.15
      at room temperature without considering phonon scattering. In addition, we
      investigate the thermally-controlled magnetic distributions in the ZGNR-based
      spin valve and find that the magnetic distribution, especially the local magnetic
      moment around the Ni atom, is strongly related to the thermal bias. The very
      large, multi-valued and controllable thermal magnetoresistance and Seebeck
      effects indicate the strong potential of ZGNR-based spin valves for extremely low
      power consuming spin caloritronics applications. The thermally-controlled
      magnetic moment in the ZGNR-based spin valve indicates its possible applications
      for information storage.

PMID- 23151966
TI  - Purification and biochemical characterization of a novel alkaline (phospho)lipase
      from a newly isolated Fusarium solani strain.
AB  - An extracellular lipase from Fusarium solani strain (F. solani lipase (FSL)) was
      purified to homogeneity by ammonium sulphate precipitation, gel filtration and
      anion exchange chromatography. The purified enzyme has a molecular mass of 30 kDa
      as estimated by sodium dodecyl sulphate polyacrylamide gel electrophoresis. The
      12 NH(2)-terminal amino acid residues showed a high degree of homology with a
      putative lipase from the fungus Necteria heamatoccocae. It is a serine enzyme,
      like all known lipases from different origins. Interestingly, FSL has not only
      lipase activity but also a high phospholipase activity which requires the
      presence of Ca(2+) and bile salts. The specific activities of FSL were about
      1,610 and 2,414 U/mg on olive oil emulsion and egg-yolk phosphatidylcholine as
      substrates, respectively, at pH 8.0 and 37  degrees C. The (phospho)lipase enzyme
      was stable in the pH range of 5-10 and at temperatures below 45  degrees C.

PMID- 23151967
TI  - Industrial waste utilization for low-cost production of raw material oil through
      microbial fermentation.
AB  - In view of ever-growing demand of biodiesel, there is an urgent need to look for
      inexpensive and promising renewable raw material oils for its production. In this
      context, the aim of this study was to evaluate the potential use of industrial
      wastes for low-cost production of oils through microbial fermentation. Among the
      strains tested, Yarrowia lipolytica grew best and produced highest lipid when
      grown on decanter effluent from palm oil mill. When crude glycerol by-product
      from a biodiesel plant was added into the effluent as a co-substrate, Y.
      lipolytica produced a higher biomass of 3.21 g/L and a higher amount of lipid of
      2.21 g/L which was 68 % of the dry weight. The scale up and process improvement
      in a 5-L bioreactor increased the biomass and lipid up to 5.53 and 2.81 g/L,
      respectively. A semi-continuous mode of operation was an effective mode for
      biomass enhancement while a fed-batch mode was effective for lipid enhancement.
      These yeast lipids have potential to be used as biodiesel feedstocks because of
      their similar fatty acid composition to that of plant oil.

PMID- 23151969
TI  - Cocaine-related health emergencies in Europe: a review of sources of information,
      trends and implications for service development.
AB  - BACKGROUND: Cocaine-related health consequences are difficult to observe. Data on
      drug users in health-emergency settings may be a useful source of information on
      consequences that are not visible via other information sources. METHODS: Thirty
      European countries submit an annual national report on the drug situation to the
      EMCDDA. All reports for the period 2007-2010 were analyzed, with particular
      attention given to auditing cocaine-related mentions. Analysis was also performed
      in order to identify sources and case definitions, assess coverage, audit cases
      and, where possible, to identify long-term trends. RESULTS: Considerable
      heterogeneity existed between countries in their approach to recording drug
      related emergencies, with only Spain and the Netherlands having established
      formal indicators. The highest annual numbers of cocaine-related episodes were
      reported by the UK (3,502), Spain (2,845) and the Netherlands (1,211). A
      considerable (2- to 3-fold) increase in the numbers of cocaine-related episodes
      has been reported since the end of the 1990s in these countries; these increases
      peaked in Spain and England around 2007/08. CONCLUSIONS: The analysis reported
      here suggests the need to develop more standardized approaches to monitoring drug
      related emergencies. It points to the potential value of developing effective
      referral links between the emergency and specialized drug services working with
      cocaine users.

PMID- 23151968
TI  - Imaging of acute pulmonary embolism.
AB  - Acute pulmonary thromboembolism (PE) is a cardiovascular emergency associated
      with significant morbidity and a 5-35 % mortality for untreated pulmonary
      embolism. If promptly diagnosed and treated, the mortality rate can be
      significantly reduced. Diagnosis of acute PE continues to be a clinical
      challenge, with diagnostic imaging playing an important role. This review
      discusses the clinical challenges of diagnosing acute PE, presents an evidence
      based review of the current tests and ever-evolving imaging technology, and
      highlights special considerations related to radiation dose, contrast media use,
      and pregnant patients.

PMID- 23151971
TI  - Maternal serum placental growth factor at 11-13 weeks' gestation and fetal
      cardiac defects.
AB  - OBJECTIVE: To investigate the relationship between fetal heart defects and
      maternal serum placental growth factor (PlGF), a marker of placental
      angiogenesis. METHODS: Maternal serum PlGF, pregnancy-associated plasma protein-A
      (PAPP-A) and uterine artery pulsatility index (UtA-PI) at 11-13 weeks' gestation
      were compared in 68 cases of isolated fetal major heart defects and 340 normal
      controls. Variables were converted into multiples of the median (MoM) after
      adjustment for gestational age, maternal age, racial origin, weight, parity and
      method of conception, and then compared between groups. The cardiac defects
      included 11 cases of obstruction of the left ventricular outflow tract (LVOT), 25
      conotruncal abnormalities and 32 valve defects. RESULTS: The median PlGF-MoM in
      the heart defect group was lower than in controls (0.80 (interquartile range
      (IQR), 0.57-1.08) vs 1.00 (IQR, 0.79-1.32); P < 0.0001). Low PlGF levels were
      observed in the presence of conotruncal and valve defects but not in the presence
      of LVOT defects. There was no significant difference between the group with fetal
      heart defects and controls in PAPP-A-MoM (0.95 (IQR, 0.68-1.28) vs 1.01 (IQR,
      0.70-1.39); P = 0.292) or UtA-PI-MoM (1.01 (IQR, 0.84-1.28) vs 0.99 (IQR, 0.80
      1.20); P = 0.396). CONCLUSION: In pregnancies with isolated fetal heart defects
      there is evidence of impaired placental angiogenesis in the absence of impaired
      placental perfusion and function.

PMID- 23151970
TI  - Adapting to climate change on Western public lands: addressing the ecological
      effects of domestic, wild, and feral ungulates.
AB  - Climate change affects public land ecosystems and services throughout the
      American West and these effects are projected to intensify. Even if greenhouse
      gas emissions are reduced, adaptation strategies for public lands are needed to
      reduce anthropogenic stressors of terrestrial and aquatic ecosystems and to help
      native species and ecosystems survive in an altered environment. Historical and
      contemporary livestock production-the most widespread and long-running commercial
      use of public lands-can alter vegetation, soils, hydrology, and wildlife species
      composition and abundances in ways that exacerbate the effects of climate change
      on these resources. Excess abundance of native ungulates (e.g., deer or elk) and
      feral horses and burros add to these impacts. Although many of these consequences
      have been studied for decades, the ongoing and impending effects of ungulates in
      a changing climate require new management strategies for limiting their threats
      to the long-term supply of ecosystem services on public lands. Removing or
      reducing livestock across large areas of public land would alleviate a widely
      recognized and long-term stressor and make these lands less susceptible to the
      effects of climate change. Where livestock use continues, or where significant
      densities of wild or feral ungulates occur, management should carefully document
      the ecological, social, and economic consequences (both costs and benefits) to
      better ensure management that minimizes ungulate impacts to plant and animal
      communities, soils, and water resources. Reestablishing apex predators in large,
      contiguous areas of public land may help mitigate any adverse ecological effects
      of wild ungulates.

PMID- 23151972
TI  - Mental health disorders influence admission rates for pain in children with
      sickle cell disease.
AB  - BACKGROUND: Patients with sickle cell disease (SCD) experience a broad range of
      mental health disorders placing them at risk for more complicated
      hospitalizations for pain. The current study examined the impact of mental health
      disorders on admission rates and hospital length of stay (LOS) for vaso-occlusive
      pain events (VOE) in pediatric patients with SCD. PROCEDURE: Patients (5-18 years
      old) with a primary discharge diagnosis of SCD with crisis were acquired through
      the Pediatric Health Information System and categorized by history of mental
      health disorders (mood disorder, anxiety disorder, disruptive behavior disorder,
      and substance use disorder). Using a retrospective cohort design, hospital
      admission rates for VOE were examined as the primary outcome and LOS as a
      secondary outcome. RESULTS: A total of 5,825 patients accounted for 23,561
      admissions for SCD with crisis with approximately 8% of the patients having a
      mental health diagnosis. Longer LOS was found among patients with a history of
      any mental health diagnosis (P < 0.0001) and within the mood disorder (P <
      0.0001), anxiety disorder (P < 0.0001), and substance use disorder (P = 0.01)
      subtypes. Hospital admissions rates for VOE were higher among patients with a
      history of any mental health diagnosis (P < 0.0001) and within the mood disorder
      (P < 0.0001), anxiety disorder (P < 0.0001), disruptive behavior disorder (P =
      0.002), and substance use disorder (P < 0.0001) subtypes. CONCLUSIONS: Pediatric
      patients with SCD and a history of a mental health diagnosis have longer LOS and
      higher admission rates for management of VOE. Ultimately, these findings suggest
      that mental health pose a challenge to the management of sickle cell pain.

PMID- 23151973
TI  - Design, synthesis and preclinical evaluation of NRC-AN-019.
AB  - Imatinib mesylate is the first tyrosine kinase inhibitor developed and approved
      for the treatment of chronic myeloid leukemia (CML). In the past few years
      development of resistance towards imatinib mesylate has been reported. To
      overcome this problem a series of phenyl amino pyrimidine derivatives have been
      designed, prepared and evaluated for anti-proliferative activity against the BCR
      ABL-positive leukemia cell line K562. Among these phenyl amino pyrimidine
      derivatives, NRC-AN-019 has been found to be a promising new lead compound for
      the therapy of imatinib mesylate-resistant chronic myeloid leukemia. In this
      communication, we describe the design, preparation and preclinical studies of NRC
      AN-019.

PMID- 23151974
TI  - Smac peptide potentiates TRAIL- or paclitaxel-mediated ovarian cancer cell death
      in vitro and in vivo.
AB  - Second mitochondria-derived activator of caspases (Smac) is a recently identified
      protein that is released from mitochondria in response to apoptotic stimuli and
      promotes apoptosis by antagonizing the inhibitor of apoptosis proteins (IAPs).
      Our previous study showed that ectopic overexpression of Smac sensitizes drug
      resistant tumor cells to TRAIL- or paclitaxel-induced apoptosis in vitro. The
      present study was designed to explore the effect of the synthesized Smac N7
      peptide in a human ovarian cancer cell line and xenograft model. The results
      showed that the single-agent Smac N7 had a non-cytotoxic effect, but it
      effectively enhanced TRAIL- or paclitaxel-induced inhibition of cell
      proliferation in a dose-dependent manner, even in TRAIL-resistant A2780 cells.
      When Smac N7 was combined with TRAIL or paclitaxel in treating A2780 cell tumor
      xenografts, synergistic anticancer effects were achieved. Furthermore, the
      combination therapy caused less damage in normal tissues and more apoptosis in
      tumor xenografts compared with TRAIL or paclitaxel alone. Increased apoptosis was
      associated with the downregulation of XIAP, survivin and the increased activity
      of caspase-3, along with an increased amount of cleaved PARP. In conclusion, this
      Smac N7 peptide is a promising candidate for ovarian cancer combination therapy,
      and Smac may be the target for the development of a novel class of anticancer
      drugs.

PMID- 23151975
TI  - CZE study on adsorption processes of aliphatic and aromatic amines on PMMA chip.
AB  - Adsorption processes on a PMMA chip linked with CZE separations of a group of 13
      aliphatic and aromatic mono- and di-amines were studied. Due to the lack of
      chromophores within aliphatic amines, contact conductivity detection implemented
      directly onto the chip was used for monitoring of cationic CZE separations. To
      prevent an adsorption of studied amines to the chip channels, the surface of PMMA
      chip was modified by dynamic coating. Different surface modifiers, such as
      aliphatic oligoamines (diethylenetriamine and triethylenetetramine), were added
      to the BGE solutions filling the chip channels. The effect of various
      concentrations of surface modifiers on peak profiles and separation parameters of
      amines was monitored. Of these, mainly, aliphatic di-amines and aromatic mono
      amines adversely affected the CZE resolution of a whole group of analytes by
      their strong adsorption to the chip channels. A propionate BGE with pH 3.2
      containing 100 MUM triethylenetetramine and 25 mM 18-crown-6-ether was found
      suitable for CZE resolution of 12 from a total of 13 amines studied. Simple
      dynamic modification of the surface of PMMA chip enabled fast (analysis time
      lasted 9 min), sensitive (sub-MUM LODs reached) and reproducible (1-3% RSD of the
      peak areas) CZE analysis of the aliphatic and aromatic amines.

PMID- 23151979
TI  - Cytarabine and clofarabine after high-dose cytarabine in relapsed or refractory
      AML patients.
AB  - Clofarabine has been shown to be effective in AML patients, either as single
      agent or, mainly, in association with intermediate dose cytarabine. Based on
      these reports, we conducted a preliminary study combining clofarabine and
      intermediate dose cytarabine in AML patients who relapsed or failed to respond to
      at least two induction therapies. We treated 47 patients affected by
      relapsed/refractory AML with a regimen including clofarabine at 22.5 mg/m(2)
      daily on days 1-5, followed after 3 hr by cytarabine at 1 g/m(2) daily on days 1
      5. Ten patients received a further consolidation cycle with clofarabine at 22.5
      mg/m(2) and cytarabine at 1 g/m(2) day 1-4. Among the 47 patients, 24/47 (51%)
      achieved a complete remission, 5/47 (10.5%) a partial response, 10/47 (21%) had a
      resistant disease, and 6/47 (13%) died of complications during the aplastic
      phase. The most frequent nonhematologic adverse events were vomiting, diarrhea,
      transient liver toxicity, febrile neutropenia, and infections microbiologically
      documented. Among the 24 patients who obtained a CR 13 underwent allogeneic bone
      marrow transplantation. In 14 patients, complete remission duration was shorter
      than 12 months, whereas 10 patients experienced longer complete remission
      duration. These very preliminary results suggest that clofarabine-cytarabine
      regimen is effective in this particularly poor prognosis category of patients,
      representing a potential "bridge" toward bone marrow transplant procedures.
      Safety data were consistent with previously reported salvage therapies. Further
      studies and a longer follow up are warranted.

PMID- 23151980
TI  - Hodgkin lymphoma: 2012 update on diagnosis, risk-stratification, and management.
AB  - DISEASE OVERVIEW: Hodgkin lymphoma (HL) is an uncommon B-cell lymphoid malignancy
      affecting 9,000 new patients annually and representing approximately 11% of all
      lymphomas in the United States. DIAGNOSIS: HL is composed of two distinct disease
      entities; the more commonly diagnosed classical HL and the rare nodular
      lymphocyte predominant HL. Nodular sclerosis, mixed cellularity, lymphocyte
      depletion, and lymphocyte-rich HL are subgroups under the designation of
      classical HL. RISK STRATIFICATION: An accurate assessment of the stage of disease
      in patients with HL is critical for the selection of the appropriate therapy.
      Prognostic models that identify patients at low or high risk for recurrence are
      used to optimize therapy for patients with limited or advanced stage disease.
      RISK-ADAPTED THERAPY: Initial therapy for HL patients is based on the histology
      of the disease, the anatomical stage and the presence of poor prognostic
      features. Patients with early stage disease are treated with combined modality
      strategies utilizing abbreviated courses of combination chemotherapy followed by
      involved-field radiation therapy, while those with advanced stage disease receive
      a longer course of chemotherapy often without radiation therapy. MANAGEMENT OF
      REFRACTORY DISEASE: High-dose chemotherapy (HDCT) followed by an autologous stem
      cell transplant (ASCT) is the standard of care for most patients who relapse
      following initial therapy. For patients who fail HDCT with ASCT, brentuximab
      vedotin, palliative chemotherapy, non-myeloablative allogeneic transplant or
      participation in a clinical trial should be considered.

PMID- 23151982
TI  - Quality of reporting of randomization methodology in nephrology trials.

PMID- 23151984
TI  - Modulation of apoptosis by ischemic preconditioning: an emerging role for miR-21.
AB  - Ischemic preconditioning (IPC) is a powerful phenomenon whereby an episode of
      ischemic injury protects the kidney from subsequent injury. Xu et al. provide new
      insights into the protective effects of delayed IPC and its inhibition of
      apoptosis by implicating a modulatory role for the microRNA miR-21. This study
      adds another layer to our understanding of IPC, but also hints at the complexity
      of the system triggered by this process.

PMID- 23151985
TI  - Strategies to reverse endothelial dysfunction in diabetic nephropathy.
AB  - Endothelial dysfunction underlies the basic pathophysiology of microvascular
      complications of diabetes. Endothelial dysfunction is associated with impaired
      nitric oxide (NO) availability. Since NO production is tightly regulated by
      endothelial nitric oxide synthase (eNOS), several therapeutic strategies have
      been investigated and proposed to improve eNOS bioavailability in the
      vasculature. The findings of Cheng et al. suggest that increased availability of
      eNOS may be an effective strategy in restoring endothelial function in patients
      with diabetic nephropathy.

PMID- 23151986
TI  - Lixivaptan: a vasopressin receptor antagonist for the treatment of hyponatremia.
AB  - Hyponatremia, the most common electrolyte disorder encountered in clinical
      practice, is associated with significant morbidity and mortality. The
      introduction of medications that specifically antagonize the vasopressin V2
      receptor (vaptans) has provided a safe and effective means of therapy. Lixivaptan
      is the newest of these agents that reliably increase serum sodium levels in
      patients with euvolemic hyponatremia. However, significant questions remain
      regarding the specific indications for vaptans, and their potential impact on
      morbidity and mortality associated with hyponatremia.

PMID- 23151987
TI  - Of veins, valves, and vascular access!

PMID- 23151988
TI  - The Case. Unusual cause of chronic renal failure with elevated liver enzymes.

PMID- 23151989
TI  - Acute hepatitis C in an HIV-infected patient: a case report and review of
      literature.
AB  - With the decrease in transmission via transfusions and injection drug use, acute
      symptomatic hepatitis C is infrequently seen in developed countries. We report a
      case of a human immunodeficiency virus (HIV)-infected adult who presented with
      abdominal pain. His alanine aminotransferase was greater than sixty times the
      upper limit of normal without any evidence on examination of fulminant hepatic
      failure. His workup revealed an elevated hepatitis C viral level with a negative
      hepatitis C antibody. He was discharged once his liver function tests improved.
      As an outpatient, he had a recurrent bout of symptoms with an elevation of his
      alanine aminotransferase and hepatitis C viral levels that promoted anti
      hepatitis C virus treatment. This case illustrates the importance of considering
      acute hepatitis C as a cause of acute hepatitis in HIV-infected men who have sex
      with men. While patients with acute symptomatic hepatitis C generally have a
      higher rate of spontaneous viral clearance compared to those with an insidious
      acute infection, most still progress to chronic hepatitis C infection, and
      patients with HIV coinfection carry a higher risk of progression to chronic
      disease.

PMID- 23151991
TI  - Bench to bedside translation of antibody drug conjugates using a multiscale
      mechanistic PK/PD model: a case study with brentuximab-vedotin.
AB  - To build a multiscale mechanism based pharmacokinetic-pharmacodynamic (PK/PD)
      model for antibody drug conjugates (ADCs), using brentuximab-vedotin as an
      example, for preclinical to clinical translation of ADC efficacy. Brentuximab
      vedotin experimental data, collected from diverse publications, were employed in
      the following steps to build and validate the model: (1) characterization of ADC
      and payload PK at the cellular level, (2) characterization of payload PK in
      plasma and tumor tissue of xenograft mouse, (3) characterization of ADC PK in
      mouse plasma, (4) prediction of the tumor payload concentrations in xenograft
      mouse by integrating parameters obtained from steps 1-3 with the novel tumor
      disposition model for ADC, (5) characterization of preclinical brentuximab
      vedotin tumor growth inhibition data using the novel PK/PD model, (6)
      characterization of ADC and payload PK in cancer patients, and (7) prediction of
      clinical responses of brentuximab-vedotin using the PK/PD model, by integrating
      PK parameters obtained from step 6, and translated mouse parameters from step 5;
      and comparing them with clinical trial results. The tumor disposition model was
      able to accurately predict xenograft tumor and plasma payload concentrations.
      PK/PD model predicted progression free survival rates and complete response rates
      for brentuximab-vedotin in patients were comparable to the observed clinical
      results. It is essential to understand and characterize the disposition of ADC
      and payload, at the cellular and physiological level, to predict the clinical
      outcome of ADC. A first of its kind mechanistic model has been developed for
      ADCs, which can integrate preclinical biomeasures and PK/PD data, to predict
      clinical response.

PMID- 23151990
TI  - Stochastic dynamic causal modeling of working memory connections in cocaine
      dependence.
AB  - Although reduced working memory brain activation has been reported in several
      brain regions of cocaine-dependent subjects compared with controls, very little
      is known about whether there is altered connectivity of working memory pathways
      in cocaine dependence. This study addresses this issue by using functional
      magnetic resonance imaging-based stochastic dynamic causal modeling (DCM)
      analysis to study the effective connectivity of 19 cocaine-dependent subjects and
      14 healthy controls while performing a working memory task. Stochastic DCM is an
      advanced method that has recently been implemented in SPM8 that can obtain
      improved estimates, relative to deterministic DCM, of hidden neuronal causes
      before convolution with the hemodynamic response. Thus, stochastic DCM may be
      less influenced by the confounding effects of variations in blood oxygen level
      dependent response caused by disease or drugs. Based on the significant regional
      activation common to both groups and consistent with previous working memory
      activation studies, seven regions of interest were chosen as nodes for DCM
      analyses. Bayesian family level inference, Bayesian model selection analyses, and
      Bayesian model averaging (BMA) were conducted. BMA showed that the cocaine
      dependent subjects had large differences compared with the control subjects in
      the strengths of prefrontal-striatal modulatory (B matrix) DCM parameters. These
      findings are consistent with altered cortical-striatal networks that may be
      related to reduced dopamine function in cocaine dependence. As far as we are
      aware, this is the first between-group DCM study using stochastic methodology.

PMID- 23151992
TI  - Adaptive support ventilation with and without end-tidal CO2 closed loop control
      versus conventional ventilation.
AB  - PURPOSE: Our aim was to compare adaptive support ventilation with and without
      closed loop control by end tidal CO2 (ASVCO2, ASV) with pressure (PC) and volume
      control ventilation (VC) during simulated clinical scenarios [normal lungs (N),
      COPD, ARDS, brain injury (BI)]. METHODS: A lung model was used to simulate
      representative compliance (mL/cmH2O): resistance (cmH2O/L/s) combinations, 45:5
      for N and BI, 60:7.7 for COPD, 15:7.7 and 35:7.7 for ARDS. Two levels of PEEP
      (cmH2O) were used for each scenario, 12/16 for ARDS, and 5/10 for others. The CO2
      productions of 2, 3, 4 and 5 mL/kg predicted body weight/min were simulated.
      Tidal volume was set to 6 mL/kg during VC and PC. Outcomes of interest were end
      tidal CO2 (etCO2) and plateau pressure (P Plat). RESULTS: EtCO2 levels in N and
      BI and COPD were similar for all modes. In ARDS, etCO2 was higher in ASVCO2 than
      in other modes (p < 0.001). Under all mechanical conditions ASVCO2 revealed a
      narrower range of etCO2. P Plat was similar for all modes in all scenarios but
      ARDS where P Plat in ASV and ASVCO2 were lower than in VC (p = 0.001). When P
      Plat was >= 28 cmH2O, P plat in ASV and ASVCO2 were lower than in VC and PC (p =
      0.024). CONCLUSION: All modes performed similarly in most cases. Minor
      differences observed were in favor of the closed loop modes. Overall, ASVCO2
      maintained tighter CO2 control. The ASVCO2 had the greatest impact during ARDS
      allowing etCO2 to increase and protecting against hypocapnia evident with other
      modes while ensuring lower P plat and tidal volumes.

PMID- 23151994
TI  - Tunable Fano resonance in symmetric multilayered gold nanoshells.
AB  - We have studied the evolution of dipole-dipole all-plasmonic Fano resonances
      (FRs) in symmetric multilayered nanoshells as a function of their geometrical
      parameters. We demonstrate that symmetry breaking is not mandatory for
      controlling the Fano resonance in such multilayer structures. By carefully
      selecting the geometrical parameters, the position of the FR can be tuned between
      600 and 950 nm and its intensity can be increased up to four fold with respect to
      the non-optimized structures. Generation of FRs in such symmetric nanostructures
      presents clear advantages over their asymmetric counterparts, as they are easier
      to fabricate and can be used in a wider range of technological applications.

PMID- 23151995
TI  - Clinical and immunologic responses in melanoma patients vaccinated with MAGE-A3
      genetically modified lymphocytes.
AB  - Cancer vaccines have recently been shown to induce some clinical benefits. The
      relationship between clinical activity and anti-vaccine T cell responses is
      somewhat controversial. Indeed, in many trials it has been documented that the
      induction of vaccine-specific T cells exceeds the clinical responses observed.
      Here, we evaluate immunological and clinical responses in 23 MAGE-A3(+) melanoma
      patients treated with autologous lymphocytes genetically engineered to express
      the tumor antigen MAGE-A3 and the viral gene product thymidine kinase of the
      herpes simplex virus (HSV-TK). HSV-TK was used as safety system in case of
      adverse events and as tracer antigen to monitor the immune competence of treated
      patients. The increase of anti-TK and anti-MAGE-A3 T-cells after vaccination was
      observed in 90 and 27% of patients, respectively. Among 19 patients with
      measurable disease, we observed a disease control rate of 26.3%, with one
      objective clinical response, and four durable, stable diseases. Three patients
      out of five with no evidence of disease (NED) at the time of vaccination remained
      NED after 73+, 70+ and 50+ months. Notably, we report that only patients
      experiencing MAGE-A3-specific immune responses showed a clinical benefit.
      Additionally, we report that responder and non-responder patients activate and
      expand T cells against the tracer antigen TK in a similar way, suggesting that
      local rather than systemic immune suppression might be involved in limiting
      clinically relevant antitumor immune responses.

PMID- 23151996
TI  - Why is infant mortality higher in boys than in girls? A new hypothesis based on
      preconception environment and evidence from a large sample of twins.
AB  - Infant mortality is higher in boys than girls in most parts of the world. This
      has been explained by sex differences in genetic and biological makeup, with boys
      being biologically weaker and more susceptible to diseases and premature death.
      At the same time, recent studies have found that numerous preconception or
      prenatal environmental factors affect the probability of a baby being conceived
      male or female. I propose that these environmental factors also explain sex
      differences in mortality. I contribute a new methodology of distinguishing
      between child biology and preconception environment by comparing male-female
      differences in mortality across opposite-sex twins, same-sex twins, and all
      twins. Using a large sample of twins from sub-Saharan Africa, I find that both
      preconception environment and child biology increase the mortality of male
      infants, but the effect of biology is substantially smaller than the literature
      suggests. I also estimate the interacting effects of biology with some
      intrauterine and external environmental factors, including birth order within a
      twin pair, social status, and climate. I find that a twin is more likely to be
      male if he is the firstborn, born to an educated mother, or born in certain
      climatic conditions. Male firstborns are more likely to survive than female
      firstborns, but only during the neonatal period. Finally, mortality is not
      affected by the interactions between biology and climate or between biology and
      social status.

PMID- 23151997
TI  - Socioeconomic differences in multipartner fertility among Norwegian men.
AB  - This article analyzes male fertility, with a particular focus on multipartner
      fertility, for cohorts born 1955 to 1984 in Norway. We find that
      socioeconomically disadvantaged men have the lowest chance of becoming fathers
      and the lowest likelihood of fathering multiple children in stable unions.
      Multipartner fertility, on the other hand, is positively associated with both
      disadvantage and advantage: higher-order birth risks with a new partner are more
      prevalent among men with low as well as high socioeconomic status. An intervening
      factor among disadvantaged men may be a higher union dissolution risk, and an
      elevated risk among advantaged men may be associated with their higher
      preferences for children and other features that make these men more attractive
      to women as partners and fathers of future children.

PMID- 23151998
TI  - How many physicians do we need? A benchmark for pediatric hematology/oncology.

PMID- 23152000
TI  - The antitumor effect of human cord blood-derived dendritic cells modified by the
      livin alpha gene in lung cancer cell lines.
AB  - The growth of malignant tumors is associated with mechanisms of immune escape and
      inhibition of apoptosis. Livin is a novel member of the inhibitors of apoptosis
      (IAP) protein family that inhibits cell apoptosis. Livin is specifically
      expressed by the majority of tumor cells, but it is not expressed in normal adult
      tissues. In this study, we used umbilical cord blood (UCB)-derived dendritic
      cells (DCs) infected with a recombinant adenovirus encoding the livin gene as a
      vaccine to activate effector cells such as cytotoxic T lymphocytes (CTLs) to
      recognize and kill livin-expressing cancer cells in vitro as an improved strategy
      for overcoming the ability of these cancer cells to escape apoptosis and
      antitumor immune responses. We employed interferon-gamma (IFN-gamma) enzyme
      linked immunospot assays to confirm that our immunization strategy induced an
      antigen-specific reaction to livin and flow cytometric analysis of staining with
      Annexin V and PI to measure the cytotoxic activity of the effector cells against
      the livin-expressing lung cancer cell lines A549 and H460. Our results show that
      the recombinant adenovirus was able to promote the maturation of the UCB-derived
      DCs. This DC vaccine could activate antigen-specific T cells to produce IFN-gamma
      upon recognition of livin peptide in the context of the appropriate HLA molecule.
      The antigen-specific T cells mediate significant cytotoxicity against the cancer
      cells, but are unlikely to cause an autoimmune reaction against the human
      bronchial epithelia cells (HBE), which do not express livin.

PMID- 23152001
TI  - A dual role of Se on Cd toxicity: evidences from the uptake of Cd and some
      essential elements and the growth responses in paddy rice.
AB  - This study was carried out to investigate the effects of selenium (Se) on the
      uptake and translocation of cadmium (Cd) and essential elements in paddy rice
      (Oryza sativa L., Shuangyou 998). Selenium could alleviate/aggravate Cd toxicity
      in paddy rice, which depended on the dosages of Se and/or Cd. When Cd treatment
      level was as low as 35.6 MUM, <=12.7 MUM Se could inhibit the uptake of Cd in
      paddy rice and increase the biomass of paddy rice; however, with Cd levels
      reaching 89-178 MUM, the addition of Se resulted in increases in Cd uptake and
      exacerbated the growth of paddy rice. Cd always inhibited the uptake of Se. Cd
      alone suppressed the uptake of Ca, Mg, Mn, Cu, and Zn; however, Se reversed the
      decreases in the concentrations of the said elements, suggesting an element
      regulation mechanism to relieve Cd toxicity. Without Cd in the solution, low
      doses of Se increased the biomasses of shoots and roots at the expense of the
      more or less decreases in the concentrations of Ca, Mg, K, Fe, Mn, Cu, and shoot
      Zn, indicating an antagonistic effect of Se on these cations. The presence of Cd
      could also reverse these decreases especially at the highest treatment levels for
      both Se and Cd, also suggesting an element regulation mechanism responsible for
      the detoxification of high dosages of Se. Consequently, when Se is used to
      alleviate Cd toxicity, attention must be paid to the Cd pollution extent and
      doses of Se supplement.

PMID- 23151999
TI  - Mechanisms of memory enhancement.
AB  - The ongoing quest for memory enhancement is one that grows necessary as the
      global population increasingly ages. The extraordinary progress that has been
      made in the past few decades elucidating the underlying mechanisms of how long
      term memories are formed has provided insight into how memories might also be
      enhanced. Capitalizing on this knowledge, it has been postulated that targeting
      many of the same mechanisms, including CREB activation, AMPA/NMDA receptor
      trafficking, neuromodulation (e.g., via dopamine, adrenaline, cortisol, or
      acetylcholine) and metabolic processes (e.g., via glucose and insulin) may all
      lead to the enhancement of memory. These and other mechanisms and/or approaches
      have been tested via genetic or pharmacological methods in animal models, and
      several have been investigated in humans as well. In addition, a number of
      behavioral methods, including exercise and reconsolidation, may also serve to
      strengthen and enhance memories. By utilizing this information and continuing to
      investigate these promising avenues, memory enhancement may indeed be achieved in
      the future.

PMID- 23152002
TI  - Mercury concentration in breast milk and infant exposure assessment during the
      first 90 days of lactation in a midwestern region of Brazil.
AB  - Breast milk samples collected from 18 nursing mothers between the 15th and 90th
      day of lactation were digested in nitric acid in a microwave, and total mercury
      (THg) levels were quantified by atomic fluorescence spectrometry. Participants
      responded to a 24-h dietary recall questionnaire on the 74th and 76th day of
      lactation and to a Food Frequency Questionnaire querying the frequency of fish
      intake over the last 90 days. Usual intake was estimated using the PC-SIDE
      software package. A meal of fish was offered on the 75th day of lactation.
      Mothers' individual mean THg levels ranged from <0.76 to 22.7 ng/mL during the
      period, and the mean level for all samples (n = 142) was 6.47 +/-6.04 ng/mL. The
      multilevel mixed linear model used showed high heterogeneity of the mercury
      levels among the mothers, and THg levels did not change significantly over the
      period under study. However, a significant increase in THg levels was observed
      after the intervention with the fish meal. Exposure increased for most infants on
      the 90th day of lactation, with intakes exceeding the THg provisional tolerable
      weekly intake (PTWI) at least once during the period for 77.8 % of samples.
      Mothers consumed mostly food from the fat and grain groups, and a significant
      correlation was detected between consumption of food of these groups and breast
      milk THg levels (p = 0.006 and 0.007). A significant correlation was also found
      between vegetable consumption and carbohydrate intake and THg levels in the
      samples (p = 0.015 and 0.045, respectively). No correlation was found between
      mothers' daily fish consumption frequency and THg levels. Although this study
      showed that mercury intake by infants during lactation may exceed the
      toxicologically safe exposure level (PTWI), we nevertheless believe that the
      benefits of lactation for both the mother and the infant outweigh the eventual
      risks that this exposure may represent.

PMID- 23152003
TI  - First-trimester detection of major cardiac defects with the use of ductus venosus
      blood flow.
AB  - OBJECTIVE: To assess the best method of combining fetal nuchal translucency (NT)
      and ductus venosus (DV) blood flow measurements in the detection of major cardiac
      defects in chromosomally normal fetuses during the first-trimester scan. METHODS:
      During an 8-year period NT and DV blood flow were routinely assessed at 11-14
      weeks' gestation. Only chromosomally normal singleton pregnancies were included
      in the study. When a cardiac defect was suspected, or when increased fetal NT
      and/or absent or reversed (AR) A-wave in the DV was observed, early fetal
      echocardiography was offered. Data on routine second- and third-trimester scans,
      neonatal follow-up or postmortem examination were obtained from hospital records.
      The detection and false-positive rates for all major cardiac defects were
      calculated for several screening strategies, including: NT or DV pulsatility
      index for veins (DV-PIV) above a fixed normal centile; AR A-wave; risk based on
      NT and DV-PIV or A-wave velocity above a fixed normal centile; and combinations
      of these strategies. RESULTS: The study population included 37 chromosomally
      normal fetuses with a major cardiac defect and 12 799 unaffected pregnancies.
      Fetal NT above the 95(th) or the 99(th) centile and AR A-wave was observed in 40,
      27 and 39% of the fetuses with major cardiac defects, respectively. A 47%
      detection rate with a 2.7% false-positive rate was obtained when AR A-wave or NT
      above the 99(th) centile was used as the selection criterion. CONCLUSIONS: Half
      of major fetal cardiac defects could be detected in the first trimester if NT and
      DV Doppler are used to select 2.7% of the general pregnant population for
      extended fetal echocardiography.

PMID- 23152005
TI  - Current status of DILD in molecular targeted therapies.
AB  - Molecular targeted drugs have become the mainstream for cancer therapy, and they
      have contributed to improving the outcome for cancer patients. On the other hand,
      molecular targeted drugs are associated with a variety of adverse drug reactions.
      Drug-induced interstitial lung disease (DILD) is a typical adverse drug reaction
      that has been an important problem with regard to safety management during cancer
      treatment. In the past, there was a lack of detailed and accurate epidemiological
      data about DILD. However, most of the molecular targeted drugs have been subject
      to all-case post-marketing surveillance since gefitinib-induced ILD became a
      concern. These surveillance data present useful information about DILD, such as
      frequency of adverse events, mortality, and risk factors, and as a result, the
      epidemiological profile of DILD associated with molecular targeted drugs has
      become apparent during the past decade. Further, it has been considered that the
      principal management for DILD is early detection and cessation of the suspected
      cause. However, ILD associated with everolimus and temsirolimus requires unusual
      management; i.e., patients with asymptomatic ILD are allowed to continue
      treatment with everolimus or temsirolimus, and even after symptomatic ILD, both
      everolimus and temsirolimus are allowed to be readministered after the resolution
      of ILD. As a result of the collected data, a change has begun in the field of
      DILD associated with molecular targeted drugs. The features of DILD can differ
      for each drug, and clinicians should thus keep this information about DILD in
      mind while treating patients.

PMID- 23152004
TI  - Potent activity of the Hsp90 inhibitor ganetespib in prostate cancer cells
      irrespective of androgen receptor status or variant receptor expression.
AB  - Androgen ablation therapy represents the first line of therapeutic intervention
      in men with advanced or recurrent prostate tumors. However, the incomplete
      efficacy and lack of durable response to this clinical strategy highlights an
      urgent need for alternative treatment options to improve patient outcomes.
      Targeting the molecular chaperone heat shock protein 90 (Hsp90) represents a
      potential avenue for therapeutic intervention as its inhibition results in the
      coordinate blockade of multiple oncogenic signaling pathways in cancer cells.
      Moreover, Hsp90 is essential for the stability and function of numerous client
      proteins, a number of which have been causally implicated in the pathogenesis of
      prostate cancer, including the androgen receptor (AR). Here, we examined the
      preclinical activity of ganetespib, a small molecule inhibitor of Hsp90, in a
      panel of prostate cancer cell lines. Ganetespib potently decreased viability in
      all lines, irrespective of their androgen sensitivity or receptor status, and
      more effectively than the ansamycin inhibitor 17-allylamino-17
      demethoxygeldanamycin (17-AAG). Interestingly, while ganetespib exposure
      decreased AR expression and activation, the constitutively active V7 truncated
      isoform of the receptor was unaffected by Hsp90 inhibition. Mechanistically,
      ganetespib exerted concomitant effects on mitogenic and survival pathways, as
      well as direct modulation of cell cycle regulators, to induce growth arrest and
      apoptosis. Further, ganetespib displayed robust antitumor efficacy in both AR
      negative and positive xenografts, including those derived from the 22Rv1 prostate
      cancer cell line that co-expresses full-length and variant receptors. Together
      these data suggest that further investigation of ganetespib as a new therapeutic
      treatment for prostate cancer patients is warranted.

PMID- 23152006
TI  - Drug-induced interstitial lung disease (DILD) in molecular targeted therapy.

PMID- 23152008
TI  - Pre- and postischemic pulsed acoustic cellular expression conditioning modulates
      expression of inflammation factors in cremaster ischemia/reperfusion injury
      model.
AB  - Pulsed acoustic cellular expression (PACE) is a treatment that applies focused
      acoustic shock waves to promote tissue healing. The aim of this study was to
      assess the effect of PACE treatment on inflammatory responses in a cremaster
      muscle ischemia/reperfusion injury model. Seventeen cremaster muscle flaps were
      evaluated in four groups: nonischemic controls (n = 5), 5-hour ischemia controls
      (n = 4), preischemic (5-hour) PACE conditioning (n = 4), and postischemic (5
      hour) PACE conditioning (n = 4). The expression of proinflammatory cytokines
      (TNFalpha, IL-6, IL-1alpha, IL-1beta, GM-CSF) and chemokines (CCL3, CCL4, CXCL4)
      was assessed using TaqMan(r) real-time PCR. Expression of ELAM-1, VCAM-1, and
      ICAM-1 was assessed by immunostaining. Preischemic PACE conditioning upregulated
      expression of IL-6, CCL3, CCL4, and CXCL4, and downregulated expression of
      TNFalpha, GM-CSF, and IL-1alpha. Postischemic PACE conditioning significantly
      decreased expression of all evaluated genes. Pre- and postischemic PACE
      conditioning decreased expression of ELAM-1 and ICAM-1. Results of the study
      indicate that application of PACE conditioning may have a beneficial effect on
      the recovery of tissues subjected to the ischemia/reperfusion injury.
      Postischemic PACE conditioning revealed anti-inflammatory effect as confirmed by
      decreased expression of inflammatory cytokines, chemokines, and cell adhesion
      molecules (ELAM-1 and ICAM-1) that are responsible for leukocyte recruitment into
      ischemic tissues. Hence, PACE therapy may be used effectively in clinical
      practice as a convenient therapeutic strategy to protect tissues against
      ischemia/reperfusion related injury after microsurgical procedures of free tissue
      transfers.

PMID- 23152007
TI  - Regionally specific increased volume of the amygdala in Williams syndrome:
      evidence from surface-based modeling.
AB  - Williams syndrome (WS) is a condition caused by a contiguous deletion of
      approximately 26-28 genes from chromosome 7, and is characterized by abnormal
      social and emotional processing and abnormal structure and function of the
      amygdala. Prior studies show that the amygdala is relatively enlarged in WS, but
      very little is known regarding the regional specificity of increased amygdalar
      volume in this condition. Here we investigated the regional specificity of
      structural alterations of the amygdala in WS, compared to a typically developing
      (TD) control group. We acquired high resolution brain MRI data from 79
      participants (39 WS, 40 TD) and used a surface-based analytical modeling
      approach. The WS group exhibited several areas of increased radial expansion of
      the amygdalar surface and no areas of decreased radial expansion of the amygdalar
      surface compared to TD controls. The areas found to exhibit particularly
      increased radial expansion in WS included the bilateral posterior cortical
      nucleus, lateral nucleus, and the central nucleus. This greater regional and
      anatomical specificity of altered amygdala structure in WS contributes to a model
      relating genetic risk in WS to the development of key brain regions for social
      and emotional functioning.

PMID- 23152009
TI  - [Managing cutaneous toxicities of targeted therapies].
AB  - Molecularly targeted therapies have shown efficacy in many types of cancer, and
      the induction for their use is increasing rapidly. However, it is frequently
      associated with varied and unique cutaneous side effects, such as hand-foot
      syndrome, rash, dry skin and paronychia. These effects, when severe or mild, tend
      to terminate the therapy because they inevitably impact the quality of life of
      patients. Treatment by emollients(steroids and moisturizing creams), topical
      antibiotics(MINO), topical corticosteroids, and antihistamines are accurately
      required at the early stages. Close interaction, among prescribers,
      dermatologists and nurses, is highly recommended in order to introduce
      preventative skin care(homeostasis)based on moisture retention, clean skin, and
      protection from agents. The side effects can be diagnosed and treated early by
      the multidisciplinary team. The balances between therapeutic benefit and
      cutaneous reaction should be considered, thus allowing for potentially greater
      success of anticancer therapy.

PMID- 23152010
TI  - [Predicting drug efficacy-fluorinated pyrimidines (fluorouracil, S-1 and
      capecitabine)].
AB  - The elucidation in recent years of intracellular signaling mechanisms related to
      cancer cell growth has been accompanied by increases in both drug development and
      biomarker research. While treatment strategies using biomarkers have been
      established and put to clinical use for various types of cancers and medications,
      most are limited to drugs targeting specific molecules, and none have been
      established for traditional cytotoxic drugs. For fluoropyrimidines, the standard
      drugs used in chemotherapy for gastrointestinal cancer, biomarker research has
      been conducted on targets such as thymidylate synthase(TS), dihydropyrimidine
      dehydrogenase(DPD), and thymidine phosphorylase(TP). The results of research on
      these targets have recently been reported, albeit retrospectively, in a number of
      additional studies and large-scale clinical trials. While some studies suggested
      that there is future potential for these targets, in general, it appears that
      there are insufficient data for their clinical application as biomarkers at
      present. Given the advances made toward the realization of personalized medicine,
      the discovery of biomarkers for fluoropyrimidines is of great importance and
      warrants further study.

PMID- 23152011
TI  - [Predictive biomarkers for response to irinotecan, platinum drugs, and taxanes].
AB  - Despite extensive progress in basic and translational research, there are few
      clinically relevant predictive biomarkers for response to conventional
      chemotherapeutic agents(irinotecan, platinum drugs, taxanes)that can guide in the
      selection of an optimal chemotherapy regimen. Molecular-targeted drugs are
      designed to act on specific mutated/overexpressed molecules of cancer cells, and
      the application of predictive biomarkers for response to these drugs has been
      well explored. Conventional cytotoxic drugs also target-specific cellular
      molecules. They act on nucleic acid, enzymes related to nucleic acid metabolism,
      or microtubules. Now we can develop new predictive biomarkers for conventional
      chemotherapy using recent molecular biology techniques and molecular
      epidemiological studies. In this review, we summarize the investigation and
      application of predictive biomarkers for response to cytotoxic drugs. We focus on
      UDP-glucuronosyltransferase 1A1(UGT1A1), breast cancer resistance protein(BCRP),
      and DNA topoisomerase I (Top1)for predictive biomarkers to irinotecan therapy;
      glutathione S-transferase P1(GSTP1), excision repair cross-complementing
      1/2(ERCC1/2), and breast cancer susceptibility gene 1/2(BRCA1/2)for response to
      platinum drugs; and b-tubulin, GSTP1, and thioredoxin for taxane therapy.

PMID- 23152012
TI  - [Therapeutic biomarkers of EGFR-TKI].
AB  - Non-small cell lung cancer(NSCLC)patients with activating mutations of the
      epidermal growth factor receptor(EGFR)gene have shown a dramatic response to EGFR
      tyrosine kinase inhibitors(EGFR-TKI)such as gefitinib and erlotinib. EGFR
      activating mutations including exon 19 deletion and exon 21 L858R are recognized
      as markers ofthe sensitivity to EGFR-TKI therapy in NSCLC. However, the emergence
      of acquired resistance is virtually inevitable, thus limiting improvement in
      patient outcomes. Several acquired-resistance mechanisms and candidates,
      including exon 20 T790M secondary mutation, MET amplification, a high-level of
      HGF expression, PTEN downregulation, FAS-NF-kappaB pathway activation, epithelial
      mesenchymal transition, and conversion to small cell lung cancer, have been
      identified. Understanding the mechanisms of acquired resistance to EGFR-TKI,
      followed by the development of molecular targeted drugs that can overcome the
      resistance, could serve as an important advance for targeting EGFR, which is
      activated in NSCLC. Further studies should be performed to clarify other
      mechanisms associated with the acquired resistance to EGFR-TKI. In this review,
      we summarize recent advances in the therapeutic biomarkers to EGFR-TKI.

PMID- 23152013
TI  - [Predictive biomarkers for anti-EGFR antibodies].
AB  - The clinical significance of KRAS gene testing prior to using anti-epidermal
      growth factor receptor(EGFR)antibodies for colorectal cancer patients has been
      established in past randomized clinical trials. Thus, testing for the 7 most
      common mutations of KRAS codons 12 and 13 is now recommended as a clinical
      practice. However, pooled analysis of randomized controlled studies in Western
      countries in patients treated with cetuximab has suggested that patients with
      tumors showing the KRAS p. G13D mutation[a glycine(G)to aspartate(D)transition
      mutation] have longer overall survival and progression-free survival when
      compared to patients with other KRAS mutations. Furthermore, even among patients
      whose tumors are wild-type for KRAS codons 12 and 13, response rates are only
      13~17% for anti-EGFR antibody monotherapy. These facts suggest that additional
      activating mutations in the RAS-RAF-MAPK or PI3K-AKT-mTOR pathways may also
      confer resistance to anti-EGFR antibody therapies. Indeed, recent retrospective
      studies have shown that mutations in KRAS codon 61 and 146, BRAF, NRAS, and
      PIK3CA may also predict resistance to anti-EGFR antibodies in colorectal cancer
      patients. On the other hand, the continuous use of anti-EGFR therapies for KRAS
      wild-type patients may lead to secondary resistance. Acquired EGFR or KRAS
      mutations have occasionally been detected among specimens from these patients. We
      review the latest personalized therapy available for colorectal cancer patients
      using KRAS mutational testing. We also illustrate future perspectives for patient
      selection using KRAS, BRAF, NRAS, PIK3CA, and other mutations.

PMID- 23152014
TI  - [Serum pancreatic enzyme elevation under treatment with sorafenib].
AB  - OBJECTIVE: Sorafenib is an oral multi-kinase inhibitor of Raf-1, VEGF and PDGF
      receptors and others, resulting in tumor regression and anti-angiogenesis. We
      studied serum pancreatic enzyme increase associated with sorafenib treatment.
      PATIENTS AND METHODS: In a phase II study of Japanese patients with metastatic
      renal cell carcinoma, a total of 131 patients received sorafenib 400 mg twice per
      day. Serum levels of lipase and amylase were measured on day 7 and every 3-4
      weeks thereafter during treatment period. When grade 3 or 4 enzyme abnormalities
      were observed, ultrasound or computed tomography scan was performed to detect
      pancreatitis. RESULTS: The incidence of all-grades lipase and amylase increases
      were 55. 7% and 38. 2%, respectively, while those of grade 3 or 4 were 30. 5% and
      5. 3%, respectively. The majority of these events were observed in the first 3
      weeks of sorafenib treatment. Grade 3 or 4 lipase increase was detected in 32
      patients (24. 4%)on day 7 measurement. These abnormal elevations spontaneously
      resolved in all patients. Regarding grade 3 lipase increase, the median time to
      recovery to grade 2 and 1 were 7 and 14 days, respectively. Three patients
      required interruption of the treatment. No patient showed any clinical
      manifestation or abnormal imaging finding suggesting pancreatitis. CONCLUSION:
      Pancreatic enzyme increases observed frequently under sorafenib treatment were
      transient and asymptomatic. They were not related to symptomatic pancreatitis.

PMID- 23152015
TI  - Digestive symptoms as side effects of combination chemotherapy of docetaxel,
      nedaplatin and 5-fluorouracil for head and neck cancer.
AB  - BACKGROUND: The study was performed to determine the frequency of digestive
      symptoms in combination therapy of docetaxel, nedaplatin and 5-fluorouracil for
      head and neck cancer. METHODS: Frequencies of digestive symptoms were
      retrospectively investigated in 91 patients. Data for 203 treatment courses were
      evaluated using the JCOG/JSCO National Cancer Institute-Common Terminology
      Criteria for Adverse Events(v 4.0 in Japanese). RESULTS: The percentages of
      patients with nausea, vomiting, stomatitis, constipation, and diarrhea in the
      first course were 74%, 16%, 42%, 42%, and 13%, respectively. Nausea, vomiting and
      constipation started mostly on day 2 or 3 and peaked between day 5 and 7.
      Diarrhea and stomatitis began later and peaked between day 8 and 11. Nausea
      showed the highest frequencies, and in the late phase(day 6 to 14)of chemotherapy
      rather than the acute phase(day 1 to 5). Stratified analysis based on the
      occurrence of nausea and vomiting in previous course showed no significant
      influence in the frequency of nausea.And then, another stratified analyses showed
      higher frequency of vomiting and diarrhea in females, nausea in patients aged B65
      years old. CONCLUSION: Nausea occurred at an unexpectedly high frequency in the
      late phase of chemotherapy with docetaxel, nedaplatin and 5-fluorouracil.

PMID- 23152016
TI  - [A trial using maximum preoperative chemotherapy for metastatic colorectal
      cancer].
AB  - There are chemotherapy methods applied before operation, before and after
      operation, or after operation for metastatic colorectal cancer. But the correct
      times and periods, etc., for their administration have not been obvious. We
      perform maximum preoperative chemotherapy to control micrometastases, and
      afterwards surgically remove the metastatic lesions[including radiofrequency
      ablation(RFA)]. Complications after operation and the severity of pathological
      liver damage etc., were investigated by comparing 14 patients who received
      maximum preoperative chemotherapy(group A), with 4 patients for whom 6 courses of
      FOLFOX+bevacizumab(BV)therapy(group B)were planned. ICG15 before liver resection
      and bleeding during liver resection were not significantly different(p=0. 26 and
      p=0. 60, respectively). No severe complication after operation was seen and
      pathological liver damage was minor in both groups. No interference of maximum
      preoperative chemotherapy with BV to metastatic colorectal cancer was suggested
      from the point of view of complications after operation and the severity of
      pathological liver damage. Further investigation with many more patients is
      necessary.

PMID- 23152017
TI  - [Evaluation of palonosetron for the prevention of nausea and vomiting induced by
      colon cancer chemotherapy].
AB  - Chemotherapy-induced nausea and vomiting(CINV)is one of the side effects causing
      significant psychological and physical suffering in patients receiving
      chemotherapy. First-generation 5-HT3 receptor antagonists(ondansetron,
      granisetron and ramosetron)are available, but some patients are still not treated
      adequately. Palonosetron is a second-generation 5-HT3 receptor antagonist with a
      prolonged duration of action and a higher receptor binding affinity than first
      generation agents. In the present study, we aimed to compare the antiemetic
      efficacy of palonosetron vs. ramosetron in preventing acute and delayed CINV.
      Patients received palonosetron followed by ramosetron, and the antiemetic effects
      were evaluated by the Multinational Association of Supportive Care in Cancer
      Antiemesis Tool(MAT). A total of 22 patients with colon cancer receiving
      chemotherapy were included in the efficacy analyses. Nine patients were observed
      with acute nausea, and 11 patients with delayed nausea. Relief of symptoms was
      observed in 3 patients with acute nausea and 4 patients with delayed nausea by
      switching from ramosetron to palonosetron. There was no significant difference of
      improvement in the acute phase, there was significantly suppressed in the delayed
      phase.

PMID- 23152018
TI  - [Efficacy and toxicity of lapatinib plus capecitabine therapy in HER2-positive
      metastatic breast cancer].
AB  - We retrospectively investigated the efficacy and toxicity of lapatinib plus
      capecitabine in 45 HER2-positive breast cancer patients. The median number of
      treatment courses was 6(1-22). Brain metastasis developed in 18 cases(40%), and
      19 cases(42.2%)had received previous capecitabine treatment for metastatic breast
      cancer. The objective response rate(ORR=CR+PR)was 22.2%(10/45), and clinical
      benefit rate(CR+PR+long SD=24w)was 46.7%(21/45).The median time to
      progression(TTP)was 24.9 weeks(95% CI: 15.2 -34.6 ), and the median overall
      survival(OS)was 78.1 weeks(95% CI: 55.7 -100.5)in all 45 cases. The median TTP
      was significantly longer in patients who had not received capecitabine
      previously(30 vs 16 weeks, 95% CI: 16.3 -43.7, p=0.0051 ). There was no
      statistical difference in median OS associated with previous capecitabine
      exposure(42.7 weeks, 95% CI: 21.4 -64, p=0.057 ). The median TTP was
      significantly longer in patients who received less than 2 treatment regimens with
      trastuzumab for MBC rather than 3 regimens more(27.3 vs 16 weeks, p=0.0257 ), but
      there was no statistical difference in median OS(81 vs 40.9 weeks, p=0.26 ).
      Lapatinib in combination with capecitabine is likely more useful in patients who
      are naive to capecitabine, who received less than two regimens for metastatic
      breast cancer.

PMID- 23152019
TI  - [Assessment of contracted bladder following intravesical instillation of BCG
      (Japan)].
AB  - We assessed a situation concerning contracted bladder following intravesical
      instillation of BCG(Japan), to investigate how the disease could be prevented.
      Between March 1997 and June 2010, we selected 20 patients with clinically or
      pathologically confirmed contracted bladder to participate in the study. The
      incidence of contracted bladder tended to be higher for patients who had received
      more than 5 doses of BCG. Repeated severe bladder irritation caused by
      intravesical BCG instillation was suggested to be the major factor leading to
      contracted bladder. To prevent the onset of contracted bladder and its
      progression resulting in total cystectomy, BCG instillation should be
      discontinued in patients who have received the instillation many times and have
      developed persistent severe bladder irritation with significantly reduced bladder
      capacity. It is necessary to consider the administration of antituberculotic and
      steroid therapy for these patients quickly.

PMID- 23152020
TI  - [Reduction in oxaliplatin-related neurotoxicity by the administration of
      Keishikajutsubuto(TJ-18)and powdered processed aconite root].
AB  - Oxaliplatin (L-OHP)is an important chemotherapeutic drug for the treatment of
      colorectal cancer. Peripheral neuropathy was observed in 90% of patients who
      received L-OHP.Neuropathy often results in the discontinuation of treatment or a
      decrease the quality of life(QOL). The most effective method for reducing
      neuropathy is the discontinuation of L-OHP. To reduce neuropathy, we administered
      Keishikajutsubutou(TJ-18)with powdered processed aconite root(TJ-3023), and we
      report the effect of these compounds. The subjects comprised 11 patients with
      metastatic colorectal cancer. L-OHP(85mg/m2)was administered as part of the
      FOLFOX6(10 patients)or FOLFOX7(1 patient)regimen. All patients had experienced
      neuropathy. We administered TJ-18(7.5 g)and T-3023(1 g). After 2 weeks, the TJ
      3023 dose was increased to 2 g for nonresponders. The response was evaluated
      according to the Neurotoxicity Criteria of DEBIOPHARM. Reduction in neuropathy
      was observed in 5 cases(45.5% ). Among 6 patients whose feet and hands felt warm,
      reduction in neuropathy was observed in 5(83.3% ).

PMID- 23152021
TI  - [Cautions for pharmaceutical care in cancer patients-comparative evaluation
      between cancer and non-cancer].
AB  - Cancer patients have greater physical and mental anxiety than non-cancer patients
      because of the severity of their disease and the strong side effects of
      anticancer drugs. In this study, therefore, we sent out questionnaires to both
      cancer and noncancer patients to investigate the specific patient education for
      reducing anxiety of cancer patients, and compared the results in detail in
      Miyazaki Prefectural Miyazaki Hospital. The number of days of patient education
      was significantly more in cancer patients than in non-cancer patients. However,
      regardless of the number of days of patient education, understanding the level of
      side effects was significantly higher in cancer patients than in non-cancer
      patients. A significant correlation was shown between the relief level of
      patients and the listening level of pharmacists in both patient groups. Regarding
      the level of patient understanding, a significant correlation was shown between
      treatment methods and all of the other factors(effects of drugs, patients' degree
      of relief, pharmacists' degree of attentiveness). On the other hand, a
      significant correlation was shown only between treatment methods and effects of
      drugs on the level of understanding in non-cancer patients. These results suggest
      that characteristic patient education should be conducted for cancer patients,
      and that it would be best if it is done early on.

PMID- 23152022
TI  - [A case of effective lapatinib/capecitabine therapy for HER2-positive breast
      cancer with multiple brain metastases].
AB  - A 63-year-old woman was suffering from HER2-positive and hormone receptor
      negative breast cancer with bone metastasis. She received 16 cycles of
      paclitaxel(PTX 80mg/m2)plus trastuzumab(TRA 2mg/kg)on a 7-day cycle, and
      zoledronic acid(ZOL 4mg/body every 28 days), resulting in a near clinical
      complete response(cCR). Two years later, the patient complained of dizziness and
      nausea, and magnetic resonance imaging revealed multiple brain metastases. The
      prior treatments with PTX and TRA were changed to lapatinib(LAP)(orally at 1,
      250mg/day every day)and capecitabine(CAP)(orally at 2, 000mg/m2 every day for 2
      weeks, followed by a 1-week rest interval as 1 cycle)because of the multiple
      brain metastases. After 4 cycles of treatment, the number of brain lesions and
      the tumor sizes were significantly reduced. After 7 cycles, however, magnetic
      resonance imaging revealed the deterioration of some brain lesions. After whole
      brain irradiation(30 Gy in 10 fractions)was added to the treatment, the outcome
      was near cCR. In conclusion, combination therapy of Lap and Cap may be an
      effective treatment option for brain metastasis of HER2-positive breast cancer.

PMID- 23152023
TI  - [Bi-weekly nab-paclitaxel and trastuzumab therapy effective against recurrent
      breast cancer with multiple lung metastases in elderly patient who had previously
      undergone two chemotherapeutic regimens for treatment of metastatic disease-a
      case Report].
AB  - We herein report a 75-year-old patient with recurrent hormone-nonresponsive, HER2
      positive breast cancer who presented with multiple lung metastases. She had
      undergone a mastectomy followed by adjuvant chemotherapy with FEC, CMF, and UFT.
      Forty-six months after the surgery, multiple lung, liver, and bone metastases
      were observed. Docetaxel and trastuzumab were administered as first-line
      chemotherapy for 13 months. A partial response and stable disease were observed,
      but progressive disease in the lung and brain was subsequently revealed. The
      patient then underwent g-knife treatment for brain metastasis. Lapatinib and
      capecitabine treatment was administered as second-line chemotherapy for 9 months.
      Stable disease was observed, but progressive disease in the lung metastases with
      clinical symptoms including cough, exertional dyspnea, and general malaise was
      revealed. As third-line chemotherapy, the patient was administered low-dose, bi
      weekly nab-paclitaxel(150mg/m2)and trastuzumab therapy. Four weeks after
      beginning the nab-paclitaxel and trastuzumab treatment, the cough disappeared; 2
      months after beginning the therapy, a partialresponse in the lung metastases was
      seen. The patient is well and the treatment has been continued for 50 weeks. No
      progression has been seen. Bi-weekly nab-paclitaxel treatment appears to have few
      side effects and might be an effective treatment option for patients with
      recurrent breast cancer.

PMID- 23152024
TI  - [Liver arterial infusion chemotherapy with adjuvant trastuzumab for the
      simultaneous treatment of liver and breast cancer-a case report].
AB  - A 62-year-old woman being treated for chronic hepatitis C and high blood pressure
      was shown by computed tomography to have tumors in the lateral and medial
      segments of her liver, and in her right breast. The tumor in the lateral segment
      of the liver was excised, the tumor in the medial segment of the liver was
      treated with microwave coagulation therapy, and the breast tumor was treated with
      simple mastectomy and sentinel lymph-node biopsy. Based on pathological features,
      the liver tumors were classified as moderately differentiated liver cell
      carcinoma, and the breast tumor as estrogen receptor-negative, progesterone
      receptor-negative, and human epidermal growth factor receptor-2-positive ductal
      carcinoma. Hepatic arterial infusion chemotherapy using fluorouracil and
      cisplatin with trastuzumab as an adjuvant was administered to treat both cancers
      simultaneously. Twelve months after the operation, neither of the cancers had
      relapsed. This case suggests that when the breast cancer is human epidermal
      growth factor receptor-2-positive, trastuzumab should be administered as adjuvant
      therapy.

PMID- 23152025
TI  - [Syndrome of inappropriate secretion of ADH following chemoradiation therapy].
AB  - We report a 69-year-old female patient with pulmonary adenocarcinoma complicated
      by the syndrome of inappropriate secretion of antidiuretic
      hormone(SIADH)following systemic chemotherapy with cisplatin(CDDP)and
      vinorelbine(VNR). She was admitted to our hospital for chemo-radiotherapy for
      advanced lung cancer, and became restless 4 hours after the administration of
      CDDP and VNR. Symptoms such as restlessness and incontinence were worsening
      despite the massive infusion that was completed. Laboratory examinations on day 6
      after chemotherapy showed severe hyponatremia(107mEq/L)with decreased serum
      osmolarity(227mOsm/L)and increased urine osmolarity(452mOsm/L). The serum anti
      diuretic hormone(ADH)level was elevated to 16. 7 pg/mL despite severe
      hyponatremia. She was diagnosed with SIADH and was treated with hypertonic saline
      infusion and fluid restriction. Her restlessness and other psychiatric symptoms
      were improved. The use of carboplatin and VNR in the subsequent course did not
      develop SIADH, indicating that the SIADH was induced by CDDP. Although SIADH
      following CDDP administration is rare, the electrolyte balance should be
      carefully monitored throughout the clinical course of chemo-radiation therapy,
      when psychiatric symptoms are found in patients with lung cancer.

PMID- 23152026
TI  - [A case of pathologically complete response of esophageal carcinoma treated with
      low-dose 5-FU/CDDP as neoadjuvant chemotherapy].
AB  - The patient was a 75-year-old woman with advanced esophageal cancer and lymph
      node swelling in the mediastinum(cStage RR). We administered preoperative
      chemotherapy(5-FU 500mg/body*10, CDDP 10mg/body*10). She received the two courses
      without showing any serious side effects. The primary tumor revealed remarkable
      improvement, but the rigidity of the esophagus wall and swelling of the lymph
      nodes were not resolved, and images showed that the patient exhibited a partial
      response to the treatment. Radical resection of the esophageal carcinoma was
      performed. Pathological examination of the resected specimens revealed no
      malignant cells in the esophagus, no metastasis of the lymph node, and the
      response evaluation was grade 3. The patient showed no recurrence 4 years and
      eleven months after the operation. In lonclusion, this rare case of esophageal
      carcinoma showed a pathologically complete response when treated with low-dose 5
      FU/CDDP as neoadjuvant chemotherapy.

PMID- 23152027
TI  - [A case of advanced gastric cancer with multiple bone metastases and disseminated
      intravascular coagulation successfully treated by combination chemotherapy of S-1
      plus docetaxel].
AB  - Advanced gastric cancer (AGC) accompanied by disseminated intravascular
      coagulation(DIC)has a poor prognosis, and has no established therapy. Here, we
      report a case of a 69-year-old woman referred to our hospital due to severe
      anemia and thrombocytopenia. Esophagogastroduodenoscopy demonstrated an AGC in
      the cardiac part of the stomach, which was histologically diagnosed as poorly
      differentiated adenocarcinoma. Bone scintigraphy showed multiple metastases to
      the bone marrow. Her diagnosis was DIC resulting from AGC, with multiple bone
      metastases. She underwent chemotherapy with the following regimen: 60mg/m2
      docetaxel(DOC)infusion on day 1 and daily oral administration of 100 mg/m2 S-1
      for two weeks every three weeks. DIC subsided rapidly after initiation of the
      therapy and resolved in 12 days. She was discharged from the hospital 56 days
      after admission and survived 303 days. To our knowledge, this is the first case
      of AGC reported in the Japanese and English literature to obtain long-term
      survival in this setting. Combined chemotherapy of S-1 plus DOC may play an
      important role in the treatment of AGC developing DIC.

PMID- 23152028
TI  - [A case of recurrent gastrointestinal stromal tumor with complete response from
      treatment with reduced dose of imatinib mesylate].
AB  - We report a patient who had a complete response by treatment with 200 mg of
      imatinib mesylate daily for peritoneal recurrences of gastrointestinal stromal
      tumor(GIST)of the stomach. On March 2007, a 68-year-old woman underwent distal
      gastrectomy for GIST of the stomach. On May 2007, peritoneal recurrences were
      recognized on CT scan, and treatment with 400 mg daily of imatinib mesylate was
      started. Because grade 2 systemic edema and rash developed one week later, the
      imatinib mesylate dose had to be reduced to 200 mg daily from July 2007. After
      reduction of imatinib mesylate, the adverse reactions resolved. Peritoneal
      dissemination disappeared on CT scan from April 2010, and complete response has
      been maintained for 18 months.

PMID- 23152029
TI  - [Effective multidisciplinary therapy mainly using S-1+ gemcitabine (GEM) for a
      case of pancreatic body cancer with multiple liver metastases].
AB  - The prognosis for pancreatic cancer with distant metastasis is not good. The case
      reported here concerns a pancreatic body cancer with multiple liver metastases
      for which multidisciplinary therapy of S-1+gemcitabine(GEM)therapy, surgery, and
      radiofrequency ablation proved to be effective, resulting in complete remission.
      The patient was a 77-year-old female. She was asymptomatic and diagnosed with
      pancreatic body cancer with multiple liver metastasis at the end of December 2008
      by ultrasonography. After careful examination, GEM 1, 200mg/body was administered
      on days 1 and 15, and S-1 was administered orally at 80mg/day for two weeks,
      followed by two weeks of rest. By the end of the 15th course, the size of the
      tumor had reduced from 26. 5mm to 14. 4mm, and all but one of the liver lesions
      disappeared; the remaining one lesion was measured as 14. 5mm by ultrasonography.
      We performed pancreas body and tail resection and radiofrequency therapy for the
      remaining single liver metastasis. After operation, GEM was administered once a
      month for 4 months. S-1 was not administered, but a new lesion was revealed at
      the S8 area by ultrasonography. We restarted S-1+GEM therapy and in 5 months the
      new lesion disappeared from image examinations. She is alive and in complete
      remission 16 months after the operation.

PMID- 23152030
TI  - Primary diffuse large B-Cell lymphoma of the prostate presenting with urinary
      retention and dyschezia for which rituximab-combined CHOP therapy was effective-a
      case presentation.
AB  - We report the case of a 66-year-old man with primary diffuse large B-cell
      lymphoma of the prostate presenting with urinary retention and dyschezia as first
      manifestation. Although a colostomy was needed due to rectal obstruction,
      rituximab-combined chemotherapy resulted in complete remission. He underwent
      stoma closure safely and has remained in complete remission for over 3years.
      Primary prostatic lymphoma is extremely rare, presenting as 0.1% of newly
      diagnosed lymphomas, but rituximab-containing chemotherapy seems to be as
      effective as for nodal lymphoma.

PMID- 23152031
TI  - [Successful chemotherapy with a docetaxel regimen for primary signet-ring cell
      carcinoma of the urinary bladder-a case report].
AB  - Primary signet-ring cell carcinoma of the bladder is rare and has a poor
      prognosis. In addition, there are few successful chemotherapies for it. We report
      a case of chemotherapy with a docetaxel regimen which was efficacious in a 64
      year-old Japanese man suffering from the disease. The onset of bilateral
      hydronephrosis led to the detection of his bladder tumor, and its pathological
      diagnosis was signet-ring cell carcinoma(immunohistochemistry showed cytokeratin
      7+/20+/-). He was treated with chemotherapy rather than with surgery because the
      tumor invaded the abdominal wall and groin. To treat his disease, we performed 2
      courses of a chemotherapy regimen comprised of S-1 and cisplatin, but it was not
      efficacious. We chose docetaxel as a second-line chemotherapy regimen,(60mg/m2,
      tri-weekly), and a clinical examination including contrast-enhanced CT showed
      that his disease had successfully responded to the chemotherapy.

PMID- 23152032
TI  - [Two cases of adult T-Cell leukemia/lymphoma with main lesion in stomach treated
      by VCAP-AMP-VECP regimen].
AB  - We report two cases of adult T-cell leukemia/lymphoma(ATLL)having their main
      lesions in the stomach. Case 1 was a 74-year-old man, complaining of left upper
      abdominal mass and pain. Upper gastrointestinal endoscopy revealed an ulcerous
      lesion in the stomach. Histological analysis and southern blotting for HTLV-1 pro
      viral DNA led us to our diagnosis of ATLL. There were no apparent lesions in the
      bone marrow and other organs. He died of tumor lysis and multi-organ failure
      shortly after treatment with the VCAP-AMP-VECP regimen. Case 2 was a 68-year-old
      man complaining of abdominal bloating and pain. Upper gastrointestinal endoscopy
      disclosed an irregularity of the gastric mucosa. A biopsy sample was diagnosed
      pathohistologically as non-Hodgkin's lymphoma. We conducted total gastrectomy.
      Based on the results from the histological study and southern blotting for HTLV-1
      p ro-viral DNA in the resected specimen, a diagnosis of ATLL was made. We treated
      him with a VCAP-AMP-VECP regimen, but multiple bone metastases and pathologic
      fracture occurred, proving that the disease was progressive. ATLL having a main
      lesion in the stomach is rare, and requires an accumulation of cases analyzed
      with careful diagnostic approach to establish a standard therapy for it.

PMID- 23152033
TI  - [Safe and effective administration of carboplatin-based chemotherapy in a patient
      undergoing hemodialysis with cancer of unknown primary by monitoring observed AUC
      of carboplatin-a case report].
AB  - Here we report a case of successful treatment with combination chemotherapy of
      carboplatin(CBDCA)and paclitaxel for a patient undergoing hemodialysis(HD)with
      cancer of unknown primary, conducted by monitoring the observed AUC of
      ultrafilterable CBDCA. CBDCA was administered at a dose of 125 mg on day 1 in
      each course, an amount which had been calculated by the Calvert formula(GFR: 0,
      target AUC: 5). HD was started at a point in time one hour after the completion
      of each CBDCA administration, and performed for 5 hours in each course. Blood
      samples were collected during the first 3 courses of chemotherapy to measure the
      plasma concentration of free-platinum. The observed AUCs(o-AUC)of CBDCA in the
      first, second and third courses were 3. 03, 3. 44 and 3. 50mg.min/mL,
      respectively. The o-AUC in the first course was lower than that in the second
      course. The o-AUC in the second course was nearly equal to that in the third
      course, while each o-AUC was below the target AUC(t-AUC). Partial response was
      achieved after two courses of the CBDCA and paclitaxel combination chemotherapy,
      with adverse events of Grade 3 neutropenia and Grade 3 peripheral neuropathy
      observed in each course after the second course of chemotherapy. o-AUC of CBDCA
      administered to HD patients can not only be below t-AUC, as in this case, but
      also oppositely above t-AUC in cases with different doses of CBDCA or HD
      settings. Our results suggest that the monitoring of o-AUC of CBDCA is useful
      when practicing CBDCA-based chemotherapy safely and effectively in cancer
      patients undergoing HD.

PMID- 23152034
TI  - Inferior pancreaticoduodenal artery aneurysms associated with occlusive lesions
      of the celiac axis: diagnosis, treatment options, outcomes, and review of the
      literature.
AB  - PURPOSE: To describe the presentation, treatment, and outcomes for 14 patients
      with aneurysms of the inferior pancreaticoduodenal arteries associated with
      occlusive lesions of the celiac axis, and to review the literature for similar
      cases. METHODS: Over a period of 12 years, 14 patients (10 women and 4 men)
      ranging in age from 26 to 50 (mean 46) years were demonstrated to have aneurysms
      of the inferior pancreaticoduodenal artery origin associated with stenosis or
      occlusion of the celiac axis. All patients were treated by a combination of
      surgery and interventional radiology. RESULTS: Outcome data collected between 3
      months and 4 years (mean 2 years) demonstrated that all aneurysms remained
      excluded, and all 14 patients were well. The 49 case reports in the literature
      confirm the findings of this cohort. CONCLUSION: In inferior pancreaticoduodenal
      artery aneurysm resulting from celiac occlusive disease, endovascular treatment
      is best achieved by stenting the celiac axis and/or embolizing the aneurysm when
      necessary.

PMID- 23152035
TI  - Complications and reinterventions in uterine artery embolization for symptomatic
      uterine fibroids: a literature review and meta analysis.
AB  - PURPOSE: To perform a literature review of the spectrum of complications
      associated with UAE relative to surgery and compare the risk of reintervention as
      well as minor, major, and overall complications. MATERIALS AND METHODS:
      Literature review was conducted in PubMed, MEDLINE, Cochrane, and CINAHL
      databases, and meta-analysis was performed. RESULTS: In randomized clinical
      trials, common complications were discharge and fever (4.00 %), bilateral uterine
      artery embolization (UAE) failure (4.00 %), and postembolization syndrome (2.86
      %). Two trials showed a significantly decreased risk in major complications with
      UAE, with odds ratios (ORs) of 0.07143 (0.009426-0.5413) and 0.5196 (0.279
      0.9678). None of the trials showed a significant difference in OR for minor
      complications of UAE. None of the trials showed a significant difference in risk
      for overall complications of UAE. Three trials showed a significantly increased
      risk for reintervention with UAE with ORs of 10.45 (2.654-41.14), 2.679 (1.289
      5.564), and 9.096 (1.269-65.18). In 76 nonrandomized studies, common
      complications were amenorrhea (4.26 %), pain (3.59 %), and discharge and fever
      (3.37 %). In 41 case studies, common complications were discharge and fever (n =
      22 cases), repeat UAE (n = 6 cases), and fibroid expulsion (n = 5 cases).
      CONCLUSION: Overall, UAE has a significantly lower rate of major complications
      relative to surgery, but it comes at the cost of increased risk of reintervention
      in the future. Educating patients about the rate and types of complications of
      UAE versus surgery, as well as the potential for reintervention, should help the
      patient and clinician come to a reasoned decision.

PMID- 23152036
TI  - Pattern of retained contrast on immediate postprocedure computed tomography (CT)
      after particle embolization of liver tumors predicts subsequent treatment
      response.
AB  - PURPOSE: To determine if the pattern of retained contrast on immediate
      postprocedure computed tomography (CT) after particle embolization of hepatic
      tumors predicts modified Response Evaluation Criteria in Solid Tumors (mRECIST)
      response. MATERIALS AND METHODS: This study was approved by the Institutional
      Review Board with a waiver of authorization. One hundred four liver tumors were
      embolized with spherical embolic agents (Embospheres, Bead Block, LC Bead) and
      polyvinyl alcohol. Noncontrast CT was performed immediately after embolization to
      assess contrast retention in the targeted tumors, and treatment response was
      assessed by mRECIST criteria on follow-up CT (average time 9.0 +/- 7.7 weeks
      after embolization). Tumor contrast retention (TCR) was determined based on
      change in Hounsfield units (HUs) of the index tumors between the preprocedure and
      immediate postprocedure scans; vascular contrast retention (VCR) was rated; and
      defects in contrast retention (DCR) were also documented. The morphology of
      residual enhancing tumor on follow-up CT was described as partial,
      circumferential, or total. Association between TCR variables and tumor response
      were assessed using multivariate logistic regression. RESULTS: Of 104 hepatic
      tumors, 51 (49%) tumors had complete response (CR) by mRECIST criteria; 23
      (22.1%) had partial response (PR); 21 (20.2%) had stable disease (SD); and 9
      (8.7%) had progressive disease (PD). By multivariate analysis, TCR, VCR, and
      tumor size are independent predictors of CR (p = 0.02, 0.05, and 0.005
      respectively). In 75 tumors, DCR was found to be an independent predictor of
      failure to achieve complete response (p < 0.0001) by imaging criteria.
      CONCLUSION: TCR, VCR, and DCR on immediate posttreatment CT are independent
      predictors of CR by mRECIST criteria.

PMID- 23152037
TI  - Recanalization of acute and subacute venous and synthetic bypass-graft occlusions
      with a mechanical rotational catheter.
AB  - PURPOSE: Percutaneous mechanical thrombectomy (PMT) is now established as an
      alternative treatment of acute arterial occlusions in addition to fibrinolysis
      and surgical thrombectomy. The objective of this retrospective study was the
      investigation of a rotational atherothrombectomy catheter in terms of safety and
      efficacy in the treatment of acute and subacute femoropopliteal bypass
      occlusions. MATERIALS AND METHODS: Forty-two patients (average age 65.8 +/- 9.1
      years) with acute (<14 days [n = 31]) and subacute (14-42 days [n = 11])
      femoropopliteal bypass occlusions were treated consecutively with a rotational
      debulking and removal catheter (Straub Rotarex). The average occlusion length was
      28.4 +/- 2.9 (24-34) cm. Thirty-four (81%) patients underwent venous bypass, and
      8 (19%) patients underwent polytetrafluoroethylene bypass. RESULTS: The technical
      success rate was 97.6% (41 of 42). In 1 patient, blood flow could not be restored
      despite the use of the atherothrombectomy system. The average catheter
      intervention time was 6.9 +/- 2.1 (4-9) min. Ankle-brachial index increased from
      0.39 +/- 0.13 to 0.83 +/- 0.11 at discharge and to 0.82 +/- 0.17 after 1 month (p
      < 0.05). There were a total of 2 (4.8%) peri-interventional complications: One
      patient developed a distal embolism, which was successfully treated with local
      lysis, and another patient had a small perforation at the distal anastomosis,
      which was successfully treated with a stent. CONCLUSION: PMT with the Rotarex
      atherothrombectomy catheter represents a safe and effective option in the
      treatment of acute and subacute femoropopliteal bypass occlusions because it can
      quickly restore blood flow.

PMID- 23152038
TI  - Transthoracic adrenal biopsy procedure using artificial carbon dioxide
      pneumothorax as outpatient procedure.
AB  - Many routes have been described for percutaneous adrenal gland biopsy. They
      require either a complex non-axial path or a long hydrodissection or even pass
      through an organ thereby increasing complications. We describe here an approach
      using an artificially-induced carbon dioxide (CO2) pneumothorax, performed as an
      outpatient procedure in a 57-year-old woman. Under local anaesthesia, 200 ml of
      CO2 was injected in the pleural space through a Veress needle under computed
      tomography fluoroscopy, to clear the lung parenchyma from the biopsy route. Using
      this technique, transthoracic adrenal biopsy can be performed under simple local
      anaesthesia as an safely outpatient procedure. 

PMID- 23152040
TI  - Ureteric embolization for lower urinary tract fistulae: use of two amplatzer
      vascular plugs and N-butyl cyanoacrylate employing the "sandwich" technique.
AB  - PURPOSE: This study describes and evaluated the effectiveness of occluding distal
      ureters in the clinical setting of urinary vaginal (vesicovaginal or
      enterovesicovaginal) fistulae utilizing a new technique which combines Amplatzer
      vascular plugs and N-butyl cyanoacrylate. MATERIALS: This is a retrospective
      study (January 2007-December 2010) of patients with urinary-vaginal fistulae
      undergoing distal ureter embolization utilizing an Amplatzer-N-butyl
      cyanoacrylate-Amplatzer sandwich technique. An 8-12-mm type-I or type-II
      Amplatzer vascular plug was delivered using the sheath and deployed in the ureter
      distal to the pelvic brim. Instillation of 0.8-1.5 cc of N-butyl cyanoacrylate
      into ureter proximal to the Amplatzer plug was performed. This was followed by
      another set of 8-12-mm type-I or type-II Amplatzer vascular plugs in a technique
      referred to as the "sandwich technique." RESULTS: Five ureters in three patients
      were occluded utilizing the above-described technique during the 4-year study
      period. Mean maximum size Amplatzer used per ureter was 10.8 mm (range, 8-12).
      One ureter required three Amplatzer plugs and the rest required two. Two patients
      (3 ureters) were clinically successful with complete resolution of symptoms in 36
      48 h. The third patient (2 ureters) was partly successful and required a second
      Amplatzer-N-butyl cyanoacrylate sandwich technique embolization. The mean
      clinical follow-up was 11.3 months (range, 1.7-29.2). CONCLUSIONS: The Amplatzer
      N-butyl cyanoacrylate-Amplatzer sandwich technique for occluding the distal
      ureter is safe and effective with a quick (probably due to the N-butyl
      cyanoacrylate) and durable (probably due to the Amplatzer plugs) clinical
      response.

PMID- 23152041
TI  - Is there a role for empiric gastroduodenal artery embolization in the management
      of patients with active upper GI hemorrhage?
AB  - PURPOSE: To assess the relative efficacy of empiric gastroduodenal artery (GDA)
      embolization in reducing recurrent hemorrhage compared to image-guided targeted
      embolization. METHODS: Data were retrospectively collected for consecutive
      patients who had catheter angiography for major upper gastrointestinal hemorrhage
      from May 2008 to November 2010 (n = 40). The total number of cases were divided
      into two main groups according to angiographic findings: those that demonstrated
      a site of hemorrhage on catheter angiography (group 1, n = 13), and those where
      the site of hemorrhage was not identified on catheter angiography (group 2, n =
      27). Group 2 was then further divided into patients who received empiric
      embolization (group 2a, n = 20) and those who had no embolization performed after
      angiography (group 2b, n = 7). RESULTS: The technical and clinical success rates
      for embolization in groups 1 and 2a were, respectively, 100 vs. 95%, and 85 vs.
      80%. There was no statistical significance in the recurrent hemorrhage rate,
      reintervention rate, or 30 day mortality between targeted and empiric
      embolization groups. There were no complications attributed to embolization
      within this study cohort. CONCLUSION: Cases of duodenal-related major upper
      gastrointestinal hemorrhage where no embolization is performed have poor outcome.
      Empiric embolization of the GDA in patients with major upper gastrointestinal
      hemorrhage refractory to endoscopic treatment appears to be a safe and effective
      treatment, with low reintervention rates and good clinical outcome comparable to
      patients where the site of hemorrhage is localized and embolized with computed
      tomographic angiography or catheter angiography and embolized.

PMID- 23152043
TI  - Subintimal recanalization of occluded stents: the substent technique.
AB  - PURPOSE: Application of metal stents is complicated by neointimal hyperplasia
      leading to vessel restenosis and reocclusion. Treatment options in cases
      presenting with complete occlusion of the stented segment and recurrent critical
      limb ischemia (CLI) are limited. We present the option of the subintimal/substent
      technique in dealing with occluded stents. METHODS: The study included patients
      presenting with recurrent CLI due to impaired blood flow as a result of complete
      occlusion of previously inserted metal stents and unsuccessful intraluminal
      crossing of the lesion via either the antegrade or retrograde approach. In these
      cases, crossing the occlusion through the subintimal/substent plane was
      attempted. Primary end points included technical success, safety of the
      procedure, clinical improvement, and limb salvage, while secondary end points
      were patient survival, primary patency, and vessel restenosis rates at 1-year
      follow-up. Study end points were calculated by Kaplan-Meier survival analysis.
      RESULTS: Between July 2006 and October 2011, a total of 14 patients (mean age
      69.14 +/- 12.59 years, 12 men) were treated with the substent technique and
      included in the analysis. Technical success rate was 85.71% (12 of 14), with a
      total lesion length of 193.57 +/- 90.78 mm. The mean occluded stented segment
      length was 90.21 +/- 44.34 mm. In 10 (83.33%) of 12 cases, a new stent had to be
      placed by the side of the old occluded one, while the remaining two cases
      (16.67%) were treated only with balloon angioplasty. No serious adverse events
      were noted during the immediate postprocedural period. All successfully treated
      patients improved clinically. Estimated limb salvage was 90.9%, and patient
      survival rate was 90.0% at 1 year's follow-up. Primary patency was 45.50% and
      vessel restenosis 77.30%. CONCLUSION: Subintimal recanalization of occluded metal
      stents through the substent plane is a valuable alternative treatment option,
      especially in patients with recurrent CLI with few alternatives.

PMID- 23152042
TI  - Below-the-ankle angioplasty and stenting for limb salvage: anatomical
      considerations and long-term outcomes.
AB  - PURPOSE: To report the long-term angiographic and clinical results in a series of
      below-the-ankle (BTA) angioplasty procedures and to present some biomechanical
      issues related to the unique anatomical geometry of the ankle. METHODS: We
      performed a retrospective analysis of BTA angioplasty procedures. Clinical end
      points included technical success, patient mortality, salvage of the treated
      foot, and repeat target lesion revascularization. Imaging end points included
      primary patency, binary restenosis of the target lesion at the 50% threshold, and
      stent integrity (stent fracture, deformation, or collapse). Univariate subgroup
      analysis was performed. RESULTS: In total, 40 limbs in 37 patients (age 73.5 +/-
      8.2 years) with critical limb ischemia were included and 42 inframalleolar
      lesions (4.2 +/- 1.4 cm) were analyzed. Technical success was achieved in 95.2%
      (40 of 42). Provisional stent placement was performed in 45.2% (19 of 42). Two
      patients died, and two major amputations occurred up to 3 years. At 1 year,
      overall primary vessel patency was 50.4 +/- 9.1%, lesion binary restenosis rate
      was 64.1 +/- 8.3%, and repeat intervention-free survival was 93.6 +/- 4.3%
      according to life table analysis of all treated lesions. Pairwise subgroup
      analysis showed that BTA self-expanding stents were associated with significantly
      higher restenosis and poorer primary patency compared to plain balloon
      angioplasty or sirolimus-eluting balloon-expandable stents. Significant
      deformation and/or fracture of balloon-expandable stents placed BTA were
      identified in five of 11. Dynamic imaging showed that the dorsalis pedis artery
      is kinked during foot dorsiflexion, whereas the distal posterior tibial artery is
      kinked during plantar flexion of the foot. CONCLUSION: BTA angioplasty for
      critical limb ischemia treatment is safe and feasible with satisfactory long-term
      results. BTA stent placement must be reserved for bailout indications.

PMID- 23152044
TI  - Localised bullous eruptions after extravasation of normal saline in the forearm
      during left ventricular device-assisted surgery.
AB  - Peripheral infusion of intravenous agents is a daily routine in hospitals.
      Extravasation is an unintended complication associated with intravenous infusion
      where accidental injection or leakage of fluid occurs into the perivascular or
      subcutaneous space. Extravasation is fairly common but is usually without serious
      consequences. This has led clinicians to underestimate the potentially serious
      consequences of extravasation. Extravasation injury results from a combination of
      factors, including cytotoxicity of the solution, osmolality, vasoconstrictor
      effects, infusion pressure and other factors. We describe a case of upper
      extremity localised bullous eruptions resulting from the pressurised infusion of
      crystalloid solutions through an intravenous catheter, placed in the operating
      room during left ventricular device-assisted surgery. Peri-operative management
      of acute localised bullous eruptions requires surveillance for unforeseen
      consequences. Early recognition, diagnosis and intervention averted potential
      complications and morbidity.

PMID- 23152045
TI  - Peri-operative physiotherapy to prevent recurrent symptoms and treatment
      following prolapse surgery: supported by evidence or not?
AB  - INTRODUCTION AND HYPOTHESIS: To provide a clinical opinion based on current
      literature reporting on the effects of peri-operative pelvic floor muscle
      training (PFMT) on postoperative pelvic floor symptoms, recurrent treatment after
      pelvic organ prolapse (POP) surgery and current clinical practice in the
      Netherlands. METHODS: The PubMed database was searched, with dates from 1966 to
      May 2012, for all types of studies reporting on the effects of peri-operative
      PFMT on recurrent treatment and/or pelvic floor symptoms after POP surgery. Also,
      current clinical practice in the Netherlands was evaluated. RESULTS: Two small
      randomised controlled trials (RCTs), with differences in the population included,
      were identified. The first RCT concluded that peri-operative PFMT reduced the
      risk of pelvic floor symptoms 12 weeks after surgery and improved the quality of
      life. The second trial concluded that there is no significant beneficial effect
      12 months after surgery. However, when looking at the reported outcomes in this
      trial micturition symptoms and quality of life improved more in the treatment
      group too. Studies evaluating whether peri-operative PFMT reduced the rate of
      recurrent treatment for POP-related symptoms, were not identified. This lack of
      evidence reflects the current clinical practice, as most gynaecologists do not
      offer peri-operative PFMT to their patients. CONCLUSIONS: Peri-operative PFMT may
      reduce the risk of pelvic floor symptoms and improve the quality of life after
      POP surgery, although evidence is insufficient to implement this in current
      clinical practice. Since the results of the two RCTs on this topic are promising,
      there is an urgent need for robust, well-designed trials to evaluate the efficacy
      and (cost-)effectiveness of peri-operative PFMT.

PMID- 23152046
TI  - Functional effect of transient transurethral catheterization on micturition in
      women: reply.

PMID- 23152047
TI  - Functional effect of transient transurethral catheterization on micturition in
      women: comment.

PMID- 23152048
TI  - Measurement of the Q-tip angle before and after tension-free vaginal tape
      obturator (TVT-O): preoperative urethral mobility may predict surgical outcome.
AB  - INTRODUCTION AND HYPOTHESIS: The purpose of this study was to compare the results
      of the Q-tip test before and after the tension-free vaginal tape-obturator (TVT
      O) in women with stress urinary incontinence (SUI) to determine the value of the
      Q-tip test in predicting the outcome of transobturator tape (TOT). METHODS:
      Between June 2008 and June 2009, 59 women with SUI who underwent the TVT-O
      procedure and were followed up for at least 6 months were analyzed. Urethral
      hypermobility was defined as a maximal straining angle greater than 30 degrees 
      as measured by the Q-tip test. Parameters of evaluation included a comprehensive
      medical history, physical examination, Q-tip test, stress test, and urodynamic
      study, which included determination of the Valsalva leak point pressure. Cure was
      defined as no leakage of urine postoperatively either subjectively or
      objectively, whereas failure was defined as the objective loss of urine during
      the stress test. RESULTS: The patients were divided into two groups according to
      their preoperative Q-tip angle: <30 degrees  (group 1, n=21) and >=30 degrees 
      (group 2, n=38). The Q-tip angle decreased significantly in both groups: from
      25.9 +/- 5.98 degrees  preoperatively to 18.4 +/- 7.23 degrees  postoperatively
      in group 1 (p=0.04) and from 36.6 +/- 6.75 degrees  preoperatively to 24.1 +/-
      5.48 degrees  postoperatively in group 2 (p=0.03). The difference was obviously
      pronounced in group 2. The incontinence cure rate was significantly higher in
      group 2 (97.4 %) than in group 1 (85.7 %; p=0.04). CONCLUSIONS: Our results
      suggest that mobility of the proximal urethra is associated with a high rate of
      success of the TVT-O procedure.

PMID- 23152049
TI  - Patient reported outcome measures in women undergoing surgery for urinary
      incontinence and pelvic organ prolapse in Denmark, 2006-2011.
AB  - INTRODUCTION AND HYPOTHESIS: The aim of this study was to evaluate the impact of
      urogynecological surgery on quality of life based on patient reported outcome
      measures (PROMs). METHODS: Data were retrieved from the Danish Urogynaecological
      Database. Inclusion criteria were Danish women undergoing surgery for urinary
      incontinence (UI) or pelvic organ prolapse (POP) from 2006 to 2011. Using
      frequency of symptoms and a visual analogue scale (VAS) both pre- and
      postoperatively, their severity of symptoms and quality of life were measured by
      questionnaires. RESULTS: During the study period, 20,629 urogynecological
      procedures were performed. The questionnaires on severity of symptoms and the VAS
      had been completed both pre- and postoperatively for approximately one third of
      women undergoing surgery. For UI surgery, 83% had improved symptoms, 13% were
      unchanged, and 4% had worse symptoms postoperatively. For POP surgery, 80, 17,
      and 3% were improved, unchanged, and worsened, respectively. The postoperative
      bother of symptoms and interference in everyday life evaluated by VAS were
      significantly reduced for both UI [preoperative median VAS score 9, postoperative
      median score 1 (p < 0.001)] and POP [8 preoperatively and 0 postoperatively (p <
      0.001)]. CONCLUSIONS: Based on PROMs, surgery for UI and POP is effective in
      alleviating symptoms associated with UI or POP, and it can improve quality of
      life in symptomatic women. Pre- and postoperative questionnaires are useful tools
      in assessing symptomatic outcome measures after surgery.

PMID- 23152050
TI  - Can levator avulsion be repaired surgically? A prospective surgical pilot study.
AB  - INTRODUCTION AND HYPOTHESIS: Avulsion of the puborectalis muscle from its bony
      insertion is common in women presenting with prolapse. We present a simple
      vaginal technique for levator reconstruction. METHODS: This is a prospective
      surgical pilot study comprising 17 patients enrolled to undergo levator repair in
      the context of prolapse surgery. This was performed through a lateral colpotomy
      at the level of the hymen using a mesh patch for reinforcement. RESULTS: We
      performed 20 levator repairs in 17 women (three bilateral). There were no
      intraoperative complications. Recovery was unremarkable in all cases. Results are
      given for a mean follow-up of 1.3 years. Most (13/17, 76 %) women were satisfied
      with the outcome. Six patients complained of symptoms of recurrent prolapse,
      three of de novo dyspareunia, and four of pain related to the repair site on
      palpation. There were two mesh erosions, one of which healed with oestrogen
      treatment. Prolapse recurrence beyond the hymen was observed in five patients.
      The mean hiatal area on Valsalva was reduced from 36.84 cm(2) to 30.71 cm(2)
      (P=0.001). CONCLUSIONS: Direct surgical repair of a levator avulsion is feasible
      at the time of prolapse surgery. However, its effect on prolapse recurrence and
      hiatal dimensions is relatively disappointing, suggesting that there often is
      microscopic trauma and functional muscle impairment in addition to the avulsion.

PMID- 23152051
TI  - Perioperative management of gynecological surgery patients: does fellow
      involvement improve performance?
AB  - INTRODUCTION AND HYPOTHESIS: Physicians-in-training play a role in guiding
      patient care, and their contributions may improve adherence to clinical practice
      guidelines. However, there is scant information in the literature assessing this
      impact on perioperative decision-making. The purpose of this study was to
      determine whether involvement of urogynecology fellows results in closer
      adherence to guidelines regarding perioperative management of gynecological
      patients. METHODS: Retrospective analysis of patients undergoing major
      gynecological surgery between 1 July 2009 and 30 June 2010. Charts were
      identified using surgical procedure codes (SPT) and subdivided into:
      urogynecology (fellow co-managed) or private gynecology patients. Information was
      collected regarding pre- and postoperative deep venous thrombosis (DVT)
      prophylaxis, preoperative antibiotic type, dose, and timing. RESULTS: Included
      were 699 women: 564 (81.2%) private and 135 (19.4%) urogynecology patients.
      Significant differences were noted in preoperative DVT prophylaxis, with the
      fellow-managed group being treated appropriately more often (p=0.001).
      Postoperative management of thromboprophylaxis, however, was not found to be
      significant (p=0.163). When evaluating antibiotic utilization, both groups were
      similar with regard to the timing of cephalosporins. However, fellows were
      significantly superior in dosing antibiotics correctly (p=0.023), and their
      selection of appropriate antibiotics for penicillin-allergic subjects approached
      significance (p=0.052). CONCLUSIONS: Fellow contributions toward clinical
      decisions resulted in more appropriate DVT prophylaxis and antibiotic
      administration prior to gynecological surgery.

PMID- 23152052
TI  - Biosensors based on nanomechanical systems.
AB  - The advances in micro- and nanofabrication technologies enable the preparation of
      increasingly smaller mechanical transducers capable of detecting the forces,
      motion, mechanical properties and masses that emerge in biomolecular interactions
      and fundamental biological processes. Thus, biosensors based on nanomechanical
      systems have gained considerable relevance in the last decade. This review
      provides insight into the mechanical phenomena that occur in suspended mechanical
      structures when either biological adsorption or interactions take place on their
      surface. This review guides the reader through the parameters that change as a
      consequence of biomolecular adsorption: mass, surface stress, effective Young's
      modulus and viscoelasticity. The mathematical background needed to correctly
      interpret the output signals from nanomechanical biosensors is also outlined
      here. Other practical issues reviewed are the immobilization of biomolecular
      receptors on the surface of nanomechanical systems and methods to attain that in
      large arrays of sensors. We then describe some relevant realizations of biosensor
      devices based on nanomechanical systems that harness some of the mechanical
      effects cited above. We finally discuss the intrinsic detection limits of the
      devices and the limitation that arises from non-specific adsorption.

PMID- 23152053
TI  - Proteasome inhibition upregulates Bim and induces caspase-3-dependent apoptosis
      in human mast cells expressing the Kit D816V mutation.
AB  - The majority of patients with systemic mastocytosis exhibit a D816V mutation in
      the activating loop of the Kit receptor expressed on mast cells. The Kit ligand
      regulates mast cell survival by transcriptional repression of the proapoptotic
      BH3-only protein Bim and by promoting Bim phosphorylation that makes it
      vulnerable for proteasomal-dependent degradation. We investigated here whether
      prevention of Bim degradation by a proteasomal inhibitor, MG132, would induce
      apoptosis in mast cells with the D816V mutation. Human umbilical cord blood
      derived mast cells (CBMCs) with wild-type (wt) Kit and two different subclones of
      the human mast cell line-1 (HMC-1) were used for the study: HMC-1.1 with the
      V560G mutation in the juxtamembrane domain and HMC-1.2 carrying the V560G
      mutation together with the D816V mutation. MG132 at 1 MUM induced apoptosis in
      all cell types, an effect accompanied by increased BH3-only proapoptotic protein
      Bim. The raise of Bim was accompanied by caspase-3 activation, and a caspase-3
      inhibitor reduced MG132-induced apoptosis. Further, MG132 caused a reduction of
      activated Erk, a negative regulator of Bim expression, and thus Bim upregulation.
      We conclude that decreased phosphorylation and increased levels of Bim overcome
      the prosurvival effect of the D816V mutation and that the results warrant further
      investigations of the clinical effects of proteasomal inhibition in systemic
      mastocytosis.

PMID- 23152054
TI  - Autophagy as a new therapeutic target in Duchenne muscular dystrophy.
AB  - A resolutive therapy for Duchene muscular dystrophy, a severe degenerative
      disease of the skeletal muscle, is still lacking. Because autophagy has been
      shown to be crucial in clearing dysfunctional organelles and in preventing tissue
      damage, we investigated its pathogenic role and its suitability as a target for
      new therapeutic interventions in Duchenne muscular dystrophy (DMD). Here we
      demonstrate that autophagy is severely impaired in muscles from patients affected
      by DMD and mdx mice, a model of the disease, with accumulation of damaged
      organelles. The defect in autophagy was accompanied by persistent activation via
      phosphorylation of Akt, mammalian target of rapamycin (mTOR) and of the autophagy
      inhibiting pathways dependent on them, including the translation-initiation
      factor 4E-binding protein 1 and the ribosomal protein S6, and downregulation of
      the autophagy-inducing genes LC3, Atg12, Gabarapl1 and Bnip3. The defective
      autophagy was rescued in mdx mice by long-term exposure to a low-protein diet.
      The treatment led to normalisation of Akt and mTOR signalling; it also reduced
      significantly muscle inflammation, fibrosis and myofibre damage, leading to
      recovery of muscle function. This study highlights novel pathogenic aspects of
      DMD and suggests autophagy as a new effective therapeutic target. The treatment
      we propose can be safely applied and immediately tested for efficacy in humans.

PMID- 23152055
TI  - USP18 is a key regulator of the interferon-driven gene network modulating
      pancreatic beta cell inflammation and apoptosis.
AB  - Type 1 diabetes (T1D) is an autoimmune disease targeting pancreatic beta cells.
      Genome-wide association studies and gene expression analysis identified
      interferon (IFN)-driven gene networks as crucial pathways in the pathogenesis of
      T1D. IFNs are linked to the response to viral infections and might contribute to
      the initiation of the autoimmune process in T1D. We presently analyzed the role
      of ubiquitin-specific peptidase 18 (USP18), an interferon-stimulated gene 15
      specific protease, on IFN-induced pancreatic beta cell inflammation and
      apoptosis. Our findings indicate that USP18 inhibition induces inflammation by
      increasing the STAT signaling and exacerbates IFN-induced beta cell apoptosis by
      the mitochondrial pathway of cell death. USP18 regulates activation of three BH3
      only proteins, namely, DP5, Bim and PUMA in pancreatic beta cells, suggesting a
      direct link between regulators of the type I IFN signaling pathway and members of
      the BCL-2 family. USP18 depletion increases the expression of the T1D candidate
      gene MDA5, leading to an upregulation of double-stranded RNA-induced chemokine
      production. These data suggest a cross talk between the type I IFN signaling
      pathway and a candidate gene for T1D to increase pro-inflammatory responses in
      beta cells. The present study shows that USP18 is a key regulator of IFN
      signaling in beta cells and underlines the importance of this pathway in beta
      cell inflammation and death.

PMID- 23152056
TI  - Sensitization to the mitochondrial pathway of apoptosis augments melanoma tumor
      cell responses to conventional chemotherapeutic regimens.
AB  - Metastatic malignant melanoma is highly resistant to chemotherapy, and the
      average survival rate is under 1 year. The only FDA-approved conventional
      chemotherapy (i.e., dacarbazine) targets melanoma tumor cells by inducing a form
      of cell death referred to as apoptosis. However, dacarbazine exhibits a response
      rate of ~5%, and combination chemotherapies consisting of cisplatin, vinblastine,
      and dacarbazine often offer little clinical advantage over dacarbazine alone.
      Apoptosis is governed by the BCL-2 family of proteins, which is comprised of anti
      apoptotic and pro-apoptotic members. To determine if the anti-apoptotic BCL-2
      repertoire established the cell death threshold and chemoresistance in melanoma,
      a novel treatment strategy was designed to inhibit the anti-apoptotic BCL-2
      members with ABT-737. Using various melanoma model systems, we determined the
      affects of ABT-737 on sensitivity to dacarbazine-based regimens. Strikingly, ABT
      737 re-sensitized melanoma cell lines to common chemotherapeutics leading to
      marked BIM-mediated apoptosis. Cellular features of the ABT-737 combination
      treatments were loss of proliferation, mitochondrial fragmentation, nuclear
      condensation, phosphatidylserine exposure, and decreased clonogenic survival. We
      also observed significant anti-tumor activity in an in vivo melanoma model
      system. Our data indicate that ABT-737 may be a beneficial adjuvant therapy to
      improve melanoma response rates when conventional chemotherapy is the only
      option.

PMID- 23152057
TI  - Prognostic impact of the expression/phosphorylation of the BH3-only proteins of
      the BCL-2 family in glioblastoma multiforme.
AB  - Apoptosis has a crucial role in anti-cancer treatment. The proteins of the BCL-2
      family are core members of the apoptotic program. Thus, we postulated that
      alterations in the expression of BCL-2 protein family, and in particular in that
      of the Bcl-2 homology domain 3 (BH3)-only proteins (which can neutralized anti
      apoptotic proteins or activate pro-apoptotic proteins) could account for
      differences in the overall survival (OS) of patients. To test this hypothesis, we
      analyzed the expression of 15 members of the BCL-2 protein family (Bax, Bak, Bok,
      Bcl-2, Bcl-xl, Bcl-w, Mcl-1, Bad, Bid, Bim, Bik, Bmf, Hrk, Noxa and Puma) in
      glioblastoma multiforme (GBM) tumors, the most frequent brain tumor in adults. We
      found that none of the individual expression of these proteins is associated with
      a significant variation in OS of the patients. However, when all BH3 proteins
      were pooled to determine a BH3(score), this score was significantly correlated
      with OS of GBM patients. We also noted that patients with a have high level of
      phospho-Bad and phospho-Bim displayed a lower OS. Thus, BH3 scoring/profiling
      could be used as an independent prognostic factor in GBM when globally analyzed.

PMID- 23152058
TI  - ZNF143 transcription factor mediates cell survival through upregulation of the
      GPX1 activity in the mitochondrial respiratory dysfunction.
AB  - Mitochondrial respiratory dysfunction has intimate relationship with redox
      regulation. The key mechanism about how the mitochondrial respiration-defective
      cells survive oxidative stress is still elusive. Here, we report that
      transcription factor zinc-finger protein 143 (ZNF143) expression and glutathione
      peroxidase (GPX) activity are markedly increased in the mitochondrial respiratory
      defective cells induced by dominant-negative DNA polymerase gamma (POLGdn). In
      this work, investigation of the cellular antioxidant glutathione (GSH) and enzyme
      GPX activity in the mitochondrial dysfunction revealed the presence of an
      increased synthesis of GSH through the activation of GCLC (glutamate-cysteine
      ligase catalytic subunit) and GCLM (glutamate-cysteine ligase regulatory subunit)
      gene expression, and also a positive upregulation of glutathione peroxidase 1
      (GPX1) activity by the transcription factor ZNF143. Significant increase in gene
      expression of SepSecS, the key enzyme responsible for selenocysteine transfer RNA
      (tRNA) synthesis, further confirmed the activation of the selenocysteine
      synthesis pathway. By using both GPX1 and ZNF143 knockdown, we provided insight
      into the involvement of ZNF143 in promoting GPX1 activity and protecting cells
      from oxidative damage and cisplatin treatment in the mitochondrial dysfunction.
      Furthermore, we reported the possible regulation of mitochondrial transcription
      factor A (TFAM) in the mitochondrial dysfunction. Our findings delineate an
      important antioxidant survival pathway that allows the mitochondrial-defective
      cells to survive oxidative stress and cisplatin treatment.

PMID- 23152059
TI  - miR-204 targets Bcl-2 expression and enhances responsiveness of gastric cancer.
AB  - Micro RNAs (miRs) are small non-coding RNAs aberrantly expressed in human tumors.
      Here, we aim to identify miRs whose deregulated expression leads to the
      activation of oncogenic pathways in human gastric cancers (GCs). Thirty nine out
      of 123 tumoral and matched uninvolved peritumoral gastric specimens from three
      independent European subsets of patients were analyzed for the expression of 851
      human miRs using Agilent Platform. The remaining 84 samples were used to validate
      miRs differentially expressed between tumoral and matched peritumoral specimens
      by qPCR. miR-204 falls into a group of eight miRs differentially expressed
      between tumoral and peritumoral samples. Downregulation of miR-204 has prognostic
      value and correlates with increased staining of Bcl-2 protein in tumoral
      specimens. Ectopic expression of miR-204 inhibited colony forming ability,
      migration and tumor engraftment of GC cells. miR-204 targeted Bcl-2 messenger RNA
      and increased responsiveness of GC cells to 5-fluorouracil and oxaliplatin
      treatment. Ectopic expression of Bcl-2 protein counteracted miR-204 pro-apoptotic
      activity in response to 5-fluorouracil. Altogether, these findings suggest that
      modulation of aberrant expression of miR-204, which in turn releases oncogenic
      Bcl-2 protein activity might hold promise for preventive and therapeutic
      strategies of GC.

PMID- 23152060
TI  - Apoptosis and necrosis: two different outcomes of cigarette smoke condensate
      induced endothelial cell death.
AB  - Cigarette smoking is one of the most important and preventable risk factors for
      atherosclerosis. However, because of the complex composition of cigarette smoke,
      the detailed pathophysiological mechanisms are not fully understood. Based on
      controversial reports on the pro-atherogenic activity of cigarette smoke
      condensate, also called tar fraction (CSC), we decided to analyse the effects of
      CSC on the viability of endothelial cells in vitro. The results of this study
      show that low concentrations of the hydrophobic tar fraction induces DNA damage
      resulting in a P53-dependent and BCL-XL-inhibitable death cascade. Western blot
      analyses showed that this cascade is caspase-independent and immunofluorescence
      analysis have shown that the apoptotic death signalling is mediated by the
      release of apoptosis-inducing factor. Higher CSC concentrations also induce
      apoptotic-like signalling but the signalling cascade is then redirected to
      necrosis. Despite the fact that CSC induces a profound increase in cellular
      reactive oxygen species production, antioxidants exhibit only a minimal cell
      death protective effect. Our data indicates that not only hydrophilic
      constituents of cigarette smoke extract, but also CSC is harmful to endothelial
      cells. The mode and the outcome of CSC-induced cell death signalling are highly
      concentration dependent: lower concentrations induce caspase-independent
      apoptosis-like cell death, whereas incubation with higher concentrations
      interrupts apoptotic signalling and induces necrosis.

PMID- 23152061
TI  - CD99 ligation upregulates HSP70 on acute lymphoblastic leukemia cells and
      concomitantly increases NK cytotoxicity.
AB  - CD99 is present in many human cell types, including high-level surface expression
      on pediatric B and T leukemias and Ewing tumors (ETs). On B lymphocytes and
      respective malignancies, its level decreases with the stage of maturation. Inter
      individual variability of CD99 on B-cell precursor acute lymphoblastic leukemia
      (BCP-ALL) blasts was shown recently to be associated with distinct cytogenetic
      backgrounds. However, CD99 targets remain mainly unknown. Here, we show that
      administration of an anti-CD99 antibody to B- and T-leukemia cell lines induces
      heat shock protein 70 (HSP70), both on the cell surface and in the cytoplasm.
      Investigation of primary BCP-ALL cells rendered similar results. Intriguingly,
      CD99-induced modulation of HSP70 on ET cells had profiles different from that on
      leukemia cells. Since HSP70 expression on tumor cells is a prerequisite for
      natural killer (NK) cell-mediated tumor lysis, we hypothesized that CD99-induced
      HSP70 may allow targeting of some CD99-positive malignancies via NK-cell
      cytotoxicity. Our experiments with NK92 cell line demonstrated that leukemia
      cells with upregulated HSP70 can be successfully killed by effector cells. We
      consider our data as a new view of CD99 functions and as a basis for the
      development of a potential anti-tumor strategy based on heat-shock protein
      activation via CD99 triggering.

PMID- 23152062
TI  - Molecular targeting of NOX4 for neuropathic pain after traumatic injury of the
      spinal cord.
AB  - Neuropathic pain is a well-known type of chronic pain caused by damage to the
      nervous system. Until recently, many researchers have primarily focused on
      identifying cellular or chemical sources of neuropathic pain or have approached
      neuropathic pain via the basis of biological study. We investigated whether both
      mmu-mir-23b (miR23b) and NADPH oxidase 4 (NOX4) antibody infusion can alleviate
      neuropathic pain by compensating for abnormally downregulated miR23b via reducing
      the expression of its target gene, NOX4, a reactive oxygen species (ROS) family
      member overexpressed in neuropathic pain. Ectopic miR23b expression effectively
      downregulated NOX4 and finally normalized glutamic acid decarboxylase 65/67
      expression. Moreover, animals with neuropathic pain showed significantly improved
      paw withdrawal thresholds (PWTs) following miR23b infusion. Normalizing miR23b
      expression in tissue lesions, caused by neuropathic pain induction, reduced
      inflammatory mediators and increased several ROS scavengers. Moreover, gamma
      aminobutyric acid (GABA)ergic neurons coexpressed suboptimal levels of miR23b and
      elevated NOX4/ROS after pain induction at the cellular level. MiR23b finally
      protects GABAergic neurons against ROS/p38/c-Jun N-terminal kinase (JNK)-mediated
      apoptotic death. By evaluating the functional behavior of mice receiving
      pain/miR23b, normal/anti-miR23b, anti-miR23b/si-NOX4, pain/NOX4 antibody,
      pain/ascorbic acid, and pain/ascorbic acid/NOX4 antibody, the positive role of
      miR23b and the negative role of NOX4 in neuropathic pain were confirmed. Based on
      this study, we conclude that miR23b has a crucial role in the amelioration of
      neuropathic pain in injured spinal cord by inactivating its target gene, NOX4,
      and protection of GABAergic neurons from cell death. We finally suggest that
      infusion of miR23b and NOX4 antibody may provide attractive diagnostic and
      therapeutic resources for effective pain modulation in neuropathic pain.

PMID- 23152063
TI  - Prevalence of vitamin D deficiency and its correlates: results of a community
      based study conducted in Karachi, Pakistan.
AB  - Of the 305 premenopausal females in a cross-sectional study in randomly selected
      communities of Karachi, Pakistan, 90.1 % showed to be vitamin D deficient. Age,
      town of residence, and housing structure were significant predictors of vitamin D
      levels. Measures to address D deficiency and its associated long latency effects
      are urgently needed. AIMS: This study aims to find out the prevalence and risk
      factors of vitamin D deficiency in community-dwelling premenopausal females in
      Karachi. METHODS: A cross-sectional study was conducted in randomly selected
      communities downtown (Saddar) and suburbs (Gulshan and Malir Town) in Karachi,
      Pakistan. Information related to sociodemographics (age, education, employment,
      and household income), housing structure, sunlight exposure, and skin
      pigmentation as well as dietary intake (using a food frequency questionnaire) was
      collected. Serum vitamins D(3) levels were also measured. Mean and SD was
      computed for continuous variables and frequency and proportions were computed for
      categorical variables. Data were further analyzed by Chi-square test and ANOVA.
      Multiple linear regression analysis was done to find out determinants of vitamin
      D (VD) levels. RESULTS: Total of 305 premenopausal females were recruited. Mean
      age, BMI, and waist circumference of the study participants was 31.97 +/- 8
      years, 25.06 +/- 5.6 kg/m(2), and 88.42 +/- 13.3 cm, respectively. Majority of
      the females were vitamin D deficient (91.50 %) with mean vitamin D levels of
      21.77 +/- 21.66 nm/L. Mean vitamin D levels were significantly different among
      females residing in downtown and suburbs. High frequency of vitamin D deficiency
      was observed in females dwelling in downtown (Saddar). According to the results
      of multiple linear regression analysis, determinants of VD levels were age, town
      of residence, and housing structure. CONCLUSION: High prevalence of vitamin D
      deficiency is seen in females in the community of Karachi, Pakistan. Age, town of
      residence, and housing structure were the significant predictors of vitamin D
      levels. Measures to combat the issue of D deficiency and its associated long
      latency effects are urgently needed.

PMID- 23152064
TI  - Risk factors for diminished bone mineral density among male hemodialysis patients
      -a cross-sectional study.
AB  - This cross-sectional study was performed to characterize the factors affecting
      bone mass in male hemodialysis subjects. We found that of all the factors
      analyzed, the strongest correlation was with body mass index. In fact, after
      adjusting for body weight, the correlations with bone turnover markers and sex
      hormones were no longer significant. PURPOSE: Abnormalities in bone and mineral
      metabolism are commonly seen in patients with end-stage renal disease, reducing
      bone quality and raising the risk of fracture. This cross-sectional study was
      performed to characterize risk factors affecting bone mass among male
      hemodialysis subjects. METHODS: For this cross-sectional study, we recruited 66
      men from three local hemodialysis units. Subjects received dual emission X-ray
      absorptiometry assessment of three sites (lumbar spine, hip, and distal radius)
      and the values were correlated with the levels of sex hormones, non-renally
      excreted bone turnover markers, and mineral metabolism markers. RESULTS: Subjects
      were found to have bone mineral density (BMD) reduced predominantly at the distal
      radius, with Z score < -2 seen in 15.4 % and T score < -2.5 in 21 % of men.
      Independent predictors of bone density included levels of bone-specific alkaline
      phosphatase and tartrate-resistant acid phosphatase 5b, which were inversely
      correlated with the femoral neck Z score. Factors positively associated with an
      increased Z score included body mass index at all sites and free estradiol levels
      at the hip and distal radius. Markers of mineral metabolism (e.g., calcium,
      phosphate, and 25-hydroxyvitamin D) were not correlated with Z scores of any site
      or with bone turnover markers. After adjusting for body weight, the associations
      between BMD, sex hormones, and bone turnover markers were no longer significant.
      CONCLUSION: We recommend that future studies seeking to assess the factors
      affecting bone strength among male hemodialysis subjects incorporate a weight
      adjusted analysis. Additionally, dialysis-dependent men receiving dual emission X
      ray absorptiometry should have the distal radius site added to the standard
      assessment.

PMID- 23152065
TI  - Phalangeal bone mineral density predicts incident fractures: a prospective cohort
      study on men and women--results from the Danish Health Examination Survey 2007
      2008 (DANHES 2007-2008).
AB  - This prospective study investigates the use of phalangeal bone mineral density
      (BMD) in predicting fractures in a cohort (15,542) who underwent a BMD scan. In
      both women and men, a decrease in BMD was associated with an increased risk of
      fracture when adjusted for age and prevalent fractures. PURPOSE: The aim of this
      study was to evaluate the ability of a compact and portable scanner using
      radiographic absorptiometry (RA) to predict major osteoporotic fractures.
      METHODS: This prospective study included a cohort of 15,542 men and women aged 18
      95 years, who underwent a BMD scan in Danish Health Examination Survey 2007-2008.
      BMD at the middle phalanges of the second, third and fourth digits of the non
      dominant hand was measured using RA (Alara MetriScan(r)). These data were merged
      with information on incident fractures retrieved from the Danish National Patient
      Registry comprising the International Classification of Diseases (ICD-10). Follow
      up was 27-45 months. Major osteoporotic fractures (vertebral fractures, humerus
      fractures, forearm fractures and hip fractures) were used in the analyses.
      Fracture events were calculated as "persons with fracture" and evaluated using
      survival analysis. RESULTS: A total of 307 (1.98 %) of the participants had
      experienced a new fracture during follow-up. BMD was significantly lower in
      subjects with fracture (0.32 vs. 0.34 g/cm(2); p < 0.001 adjusted for age,
      gender, prevalent fractures, height, weight and smoking). In both women and men,
      a 1 SD decrease in BMD (T score units) was associated with an increased risk of
      fracture when adjusted for age and prevalent fractures (women: HR = 1.39, CI 1.24
      1.54, p < 0.001; men: HR = 1.47, CI 1.20-1.79, p < 0.001). CONCLUSION: Phalangeal
      BMD as measured using RA predicts the incidence of major osteoporotic fractures.

PMID- 23152066
TI  - [Asthma bronchiale: lung function is affected by coffeine].

PMID- 23152067
TI  - [Coronary heart disease: how effective are psychological interventions?].

PMID- 23152068
TI  - [Acute coronary syndrome: does additional intake of oral anticoagulation make
      sense? Triple treatment is not indicated normally].

PMID- 23152069
TI  - [How useful are diets against cancer?].
AB  - BACKGROUND: Diets against cancer are attractive for patients who try to influence
      disease progression. METHODS: In order to determine the most influential cancer
      diets in Germany, we analyzed the chatroom for cancer patients "Krebs-Kompass",
      the search machines Google and Bing and our own counseling experience as experts.
      We conducted a systematic literature review of clinical data in Medline also
      considering preclinical data on safety. RESULTS: The most often mentioned "cancer
      diets" are Budwig diet, Gerson's regimen, lowcarb diet, cancer cure of Breubeta
      and macrobiotic diet. These diets can be classified according to the principle
      idea of carcinogenesis as follows: cancer as a lack or abundance of a substance
      or as a consequence of pathological metabolism of cancer cells. Staying in line
      with a specific diet the patients are thought to be able to cure themselves or at
      least substantially contribute to cure. However, we did not find any scientific
      publication of a clinical study which describes positive results regarding
      survival. On the contrary, data show malnutrition and side effects. CONCLUSION:
      There is no indication to consume a "cancer diet". In some cases adverse effects
      can occur. Cancer patients who are discussing nutrition should be warned about
      taking up a "cancer diet".

PMID- 23152070
TI  - [De novo left ventricular thrombus during tako-tsubo cardiomyopathy].
AB  - HISTORY AND CLINICAL FINDINGS: A 70-year-old woman complained of persistent
      angina pectoris and exertional dyspnoea after a fierce row with a dog owner. Five
      days after the conflict she visited our clinic. INVESTIGATIONS: The ECG showed T
      wave inversions across the inferior and anterior leads as well as a prolonged QTc
      interval (490 ms). NTproBNP was elevated (6733 ng/l) while troponin T was normal.
      Echocardiography and ventriculography during cardiac catheterisation demonstrated
      an impaired left ventricular function (EF 55 %) with apical akinesia. Coronary
      artery disease was ruled out by coronary angiography. Based on these findings
      stress-related cardiomyopathy (Tako-tsubo syndrome) was diagnosed. TREATMENT AND
      CLINICAL COURSE: Guideline-based therapy of heart failure was performed. At
      control examination 13 days after the initial event left ventricular function had
      improved but now a new left ventricular apical thrombus was detected. Therefore,
      oral anticoagulation therapy was started. CONCLUSION: In cases of tako-tsubo
      cardiomyopathy with apical akinesia it should be noted that a left ventricular
      thrombus can develope within few days.

PMID- 23152071
TI  - [Malaria: a medical emergency].

PMID- 23152072
TI  - [Renal failure after gastrointestinal hemorrhage: case 10/2012].
AB  - HISTORY AND ADMISSION FINDINGS: We report on a 78-year-old female patient, who
      presented to the emergency department with nausea and vomiting. INVESTIGATIONS:
      Endoscopy of the upper gastrointestinal tract revealed gastric erosions and
      duodenal ulcers. The patient had iron deficiency anemia. DIAGNOSIS, TREATMENT AND
      COURSE: Following treatment with a proton pump inhibitor (PPI) the patient
      developed fever, signs of inflammation and oliguric renal failure. In the urine
      dipstick there was minimal hematuria and leukocyturia. Urinary protein
      differentiation revealed tubular proteinuria with excretion of alpha1
      microglobulin. Renal biopsy showed interstitial nephritis with infiltration of
      eosinophilic granulocytes. After stopping treatment with PPI and commencing
      glucocorticoid therapy, the patient recovered fully from renal failure.
      CONCLUSIONS: Allergic interstitial nephritis following PPI treatment is an
      important differential diagnosis of renal failure of unknown cause and has a good
      prognosis when promptly diagnosed and treated.

PMID- 23152073
TI  - [Viral infection of hepatocytes].
AB  - Many viruses infect hepatocytes. On the one hand an understanding of the
      underlying molecular mechanisms can be used to block infection by pathogenic
      viruses, on the other hand hepatotropic viruses can be utilized in gene therapy
      approaches for the directed delivery of genetic material into hepatocytes. The
      hepatitis C virus (HCV) follows a complex cell entry route utilizing at least
      four essential cell surface receptors on hepatocytes. Inhibitors of HCV cell
      entry are in early clinical development and could useful for the prevention of
      HCV reinfection of the graft after liver transplantation. Although much less is
      known about the cell entry of hepatitis B virus and hepatitis D virus (HBV; HDV)
      it can be blocked efficiently by active or passive immunization. Moreover, a
      highly specific lipopeptide entry inhibitor based on a fragment of the HBV
      envelope is in clinical development. Finally, approaches are being developed to
      use hepatotropic viruses to correct genetic defects in hepatocytes. Especially
      adeno-associated virus based vector systems have recently shown promising results
      in proof-of-concept studies.

PMID- 23152074
TI  - Associations between adolescents' perceived discrimination and prosocial
      tendencies: the mediating role of Mexican American values.
AB  - Experiences with perceived discrimination (e.g., perceptions of being treated
      unfairly due to race or ethnicity) are expected to impact negatively youths'
      prosocial development. However, resilience often occurs in light of such
      experiences through cultural factors. The current longitudinal study examined the
      influence of perceived discrimination on the emergence of Mexican American
      adolescents' later prosocial tendencies, and examined the mediating role of
      Mexican American values (e.g., familism, respect, and religiosity). Participants
      included 749 adolescents (49 % female) interviewed at 5th, 7th, and 10th grade.
      Results of the current study suggested that, although perceived discrimination
      was associated negatively with some types of prosocial tendencies (e.g.,
      compliant, emotional, and dire) and related positively to public prosocial
      helping, the associations were mediated by youths' Mexican American values.
      Directions for future research are presented and practical implications for
      promoting adolescents' resilience are discussed.

PMID- 23152075
TI  - Early growth response 1 regulates glucose deprivation-induced necrosis.
AB  - Necrosis is commonly found in the core region of solid tumours due to metabolic
      stress such as hypoxia and glucose deprivation (GD) resulting from insufficient
      vascularization. Necrosis promotes tumour growth and development by releasing the
      tumour-promoting cytokine high mobility group box 1 (HMGB1); however, the
      molecular mechanism underlying necrotic cell death remains largely unknown. In
      this study, we show that early growth response 1 (Egr-1) is induced in a reactive
      oxygen species (ROS)-dependent manner by GD in several cell lines such as A549,
      MDA-MB-231 and HepG2 cells that exhibit necrosis upon GD. We found that Egr-1
      short hairpin RNA (shRNA) prevented GD-induced necrosis and HMGB1 release.
      Necrosis-inhibiting activity of Egr-1 shRNA was also seen in multicellular tumour
      spheroids (MTSs), an in vitro tumour model system. In contrast, Egr-1
      overexpression appeared to make tumour cells more susceptible to GD-induced
      necrosis. Finally, Egr-1 shRNA suppressed the growth of MTSs. These findings
      demonstrate that Egr-1 is implicated in GD-induced necrosis and tumour
      progression.

PMID- 23152076
TI  - St. John's wort relieves pain in an animal model of migraine.
AB  - BACKGROUND: Despite the substantial improvement that antimigraine drugs brought
      to migraineurs, there is the need for a long-acting and better tolerated migraine
      treatment than actual pharmacotherapy. St. John's wort (SJW), a medicinal plant
      endowed with a favourable tolerability profile, showed numerous bioactivities. We
      here investigated the pain-relieving property of SJW and its main components,
      hypericin and flavonoids, in a mouse model induced by nitric oxide (NO) donors
      administration. METHODS: The NO donors nitroglycerin and sodium nitroprusside
      (SNP) induced allodynia (cold plate test) and hyperalgesia (hot plate test).
      Western blotting experiments were performed to detect c-Fos and protein kinase C
      (PKC) expression within periaqueductal grey matter (PAG). RESULTS: A single oral
      administration of an SJW dried extract (5 mg/kg p.o.) produced a prolonged relief
      from pain hypersensitivity. Similarly, preventive SJW administration increased
      the latency to the induction of hyperalgesia and reduced the duration of the
      painful symptomatology. Among SJW main components, hypericin showed a similar
      profile of activity, whereas flavonoids were devoid of any antihyperalgesic
      effect. To clarify the cellular pathways involved in the SJW mechanism of action,
      we examined the effects induced by the herbal drug on PKC. NO donors'
      administration upregulated and increased phosphorylation of PKCgamma and
      PKCepsilon isoforms within PAG that was prevented by SJW treatment. The absence
      of behavioural side effects or altered animals' locomotor activity by SJW was
      demonstrated. CONCLUSIONS: These results suggest SJW as a safe therapeutic
      perspective for migraine pain, and indicate PKC as an innovative target for
      antimigraine therapy.

PMID- 23152079
TI  - Zinc oxide nanoflowers make new blood vessels.
AB  - It is well established that angiogenesis is the process of formation of new
      capillaries from pre-existing blood vessels. It is a complex process, involving
      both pro- and anti-angiogenic factors, and plays a significant role in
      physiological and pathophysiological processes such as embryonic development,
      atherosclerosis, post-ischemic vascularization of the myocardium, tumor growth
      and metastasis, rheumatoid arthritis etc. This is the first report of zinc oxide
      (ZnO) nanoflowers that show significant pro-angiogenic properties (formation of
      new capillaries from pre-existing blood vessels), observed by in vitro and in
      vivo angiogenesis assays. The egg yolk angiogenesis assay using ZnO nanoflowers
      indicates the presence of matured blood vessels formation. Additionally, it helps
      to promote endothelial cell (EA.hy926 cells) migration in wound healing assays.
      Formation of reactive oxygen species (ROS), especially hydrogen peroxide
      (H(2)O(2))-a redox signaling molecule, might be the plausible mechanism for
      nanoflower-based angiogenesis. Angiogenesis by nanoflowers may provide the basis
      for the future development of new alternative therapeutic treatment strategies
      for cardiovascular and ischemic diseases, where angiogenesis plays a significant
      role.

PMID- 23152077
TI  - Management of parastomal varices: who re-bleeds and who does not? A systematic
      review of the literature.
AB  - Although first described almost half a century ago, parastomal varices are not
      easily recognised as a cause of stomal bleeding even though they occur in up to
      5% of all people who have a stoma. The main challenges associated with this
      condition are diagnosis and management. For that reason, the aim of the present
      study was to perform a systematic review of all the available literature
      pertaining to this topic. The primary end point was recurrent variceal
      haemorrhage after a particular mode of management. Several secondary endpoints
      focused on means of diagnosis and pathological conditions of abdominal organs
      that could contribute to both the formation of these varices and the rate of re
      bleeding. Sixty-six articles comprising 210 patients were analysed. Parastomal
      varices tend to be more frequent in men manifesting with bleeding in the fifth
      decade of life. The majority (72.0%) of patients who bleed from parastomal
      varices do so from an ileostomy. The most common pathology leading to stoma
      formation is ulcerative colitis (57.8%). Liver cirrhosis is the most common cause
      of portal hypertension leading to the development of parastomal varices and
      primary sclerosing cholangitis is in second place. A third of patients with
      parastomal varices also have co-existent oesophageal varices. There are no
      pathognomonic symptoms or signs of parastomal varices and only the minority of
      patients have a raspberry appearance of the stoma, visibly dilated submucosal
      veins and bluish discoloration and hyperkeratosis of the skin around it. Venous
      phase contrast angiography or portal venography is the most successful
      radiological investigation to confirm the diagnosis. The transjugular
      intrahepatic portosystemic shunt (TIPS) procedure has the highest success rate in
      preventing recurrent haemorrhage and local measures, either non-operative or
      surgical, are the least effective. Comparison of TIPS with non-operative and
      local surgical treatment groups produced a risk reduction in 4.60 and 3.85,
      respectively. Treatment of 1.37 people with a TIPS procedure prevents one person
      suffering from recurrent variceal bleeding and using TIPS can reduce the
      likelihood of re-bleeding by 78.5%. Surgical portosystemic shunting or
      embolisation alone leaves patients with approximately 50% chance of re-bleeding.
      Although TIPS has gained popularity over the last two decades almost three
      quarters of patients with parastomal varices are still treated with local
      measures as first-line management. Liver transplantation as a treatment of the
      primary cause of parastomal varices remains very rare.

PMID- 23152078
TI  - Obstructive defecation syndrome: 19 years of experience with laparoscopic
      resection rectopexy.
AB  - BACKGROUND: In obstructive defecation syndrome (ODS) combinations of morphologic
      alterations of the pelvic floor and the colorectum are nearly always evident.
      Laparoscopic resection rectopexy (LRR) aims at restoring physiological function.
      We present the results of 19 years of experience with this procedure in patients
      with ODS. METHODS: Between 1993 and 2012, 264 patients underwent LRR for ODS at
      our department. Perioperative and follow-up data were analyzed. RESULTS: The
      female/male ratio was 25.4:1, mean age was 61.3 years (+/-14.3 years), and mean
      body mass index (BMI) was 25.2 kg/m(2) (+/-4.2 kg/m(2)). The pathological
      conditions most frequently found in combination were a sigmoidocele plus a
      rectocele (n = 79) and a sigmoidocele plus a rectal prolapse or intussusception
      (n = 69). The conversion rate was 2.3 % (n = 6). The mortality rate was 0.75 % (n
      = 2), the rate of complications requiring surgical re-intervention was 4.3 % (n =
      11), and the rate of minor complications was 19.8 % (n = 51). Follow-up data were
      available for 161 patients with a mean follow-up of 58.2 months (+/-47.1 months).
      Long-term results showed that 79.5 % of patients (n = 128) reported at least an
      improvement of symptoms. In cases of a sigmoidocele (n = 63 available for follow
      up) or a rectal prolapse II degrees /III degrees  (n = 72 available for follow
      up), the improvement rates were 79.4 % (n = 50) and 81.9 % (n = 59),
      respectively. CONCLUSIONS: LRR is a safe and effective procedure. Our
      perioperative results and long-term functional outcome strengthen the evidence
      regarding benefits of LRR in patients with an outlet obstruction. However,
      careful patient selection is essential.

PMID- 23152080
TI  - The alphaVbeta3/alphaVbeta5 integrin inhibitor cilengitide augments tumor
      response to melphalan isolated limb perfusion in a sarcoma model.
AB  - Isolated limb perfusion (ILP) with melphalan and tumor necrosis factor (TNF)
      alpha is used to treat bulky, locally advanced melanoma and sarcoma. However, TNF
      toxicity suggests a need for better-tolerated drugs. Cilengitide (EMD 121974), a
      novel cyclic inhibitor of alpha-V integrins, has both anti-angiogenic and direct
      anti-tumor effects and is a possible alternative to TNF in ILP. In this study,
      rats bearing a hind limb soft tissue sarcoma underwent ILP using different
      combinations of melphalan, TNF and cilengitide in the perfusate. Further groups
      had intra-peritoneal (i.p.) injections of cilengitide or saline 2 hr before and 3
      hr after ILP. A 77% response rate (RR) was seen in animals treated i.p. with
      cilengitide and perfused with melphalan plus cilengitide. The RR was 85% in
      animals treated i.p. with cilengitide and ILP using melphalan plus both TNF and
      cilengitide. Both RRs were significantly greater than those seen with melphalan
      or cilengitide alone. Histopathology showed that high RRs were accompanied by
      disruption of tumor vascular endothelium and tumor necrosis. Compared with ILP
      using melphalan alone, the addition of cilengitide resulted in a three to
      sevenfold increase in melphalan concentration in tumor but not in muscle in the
      perfused limb. Supportive in vitro studies indicate that cilengitide both
      inhibits tumor cell attachment and increases endothelial permeability. Since
      cilengitide has low toxicity, these data suggest the agent is a good alternative
      to TNF in the ILP setting.

PMID- 23152081
TI  - Novel method for culturing Schwann cells from adult mouse sciatic nerve in vitro.
AB  - Schwann cells (SCs) are important in the recovery of peripheral nerve injury and
      are valuable cells for the tissue engineering of artificial neurons. Clinical
      applications that require pure SCs in large quantities are limited since human
      and mouse SCs do not attach well to the wall of the culture dish and have low
      proliferative potential. To obtain high quantities of highly pure SCs, we
      developed a new method for culturing SCs from the mouse sciatic nerve in vitro.
      Approximately 1.5 cm of the bilateral sciatic nerve of a c57 adult mouse was
      surgically removed and pre-cultured in DMEM containing either 10% FBS or growth
      factors. One week later, the in vitro SC culture was observed using light
      microscopy following enzyme digestion. Cell numbers and cell attachment were
      examined. The purity of the SCs was determined using s100beta and p75NTR
      staining. Sciatic nerves that had not been pre-cultured were used as the control
      group. When the excised tissue was pre-cultured in vitro, high yields of SCs were
      obtained. The SCs were more likely to adhere and the purity was approximately 98%
      at the p1 generation following simple purification steps, which was significantly
      higher than the purity obtained from the control group. The pre-culturing of the
      sciatic nerve prior to in vitro tissue culturing significantly increased the
      quantity and quality of the SCs.

PMID- 23152082
TI  - Biomimetic hydroxyapatite coating on pore walls improves osteointegration of
      poly(L-lactic acid) scaffolds.
AB  - Polymer-ceramic composites obtained as the result of a mineralization process
      hold great promise for the future of tissue engineering. Simulated body fluids
      (SBFs) are widely used for the mineralization of polymer scaffolds. In this work
      an exhaustive study with the aim of optimizing the mineralization process on a
      poly(L-lactic acid) (PLLA) macroporous scaffold has been performed. We observed
      that when an air plasma treatment is applied to the PLLA scaffold its
      hydroxyapatite nucleation ability is considerably improved. However, plasma
      treatment only allows apatite deposition on the surface of the scaffold but not
      in its interior. When a 5 wt % of synthetic hydroxyapatite (HAp) nanoparticles is
      mixed with PLLA a more abundant biomimetic hydroxyapatite layer grows inside the
      scaffold in SBF. The morphology, amount, and composition of the generated
      biomimetic hydroxyapatite layer on the pores' surface have been analyzed. Large
      mineralization times are harmful to pure PLLA as it rapidly degrades and its
      elastic compression modulus significantly decreases. Degradation is retarded in
      the composite scaffolds because of the faster and extensive biomimetic apatite
      deposition and the role of HAp to control the pH. Mineralized scaffolds, covered
      by an apatite layer in SBF, were implanted in osteochondral lesions performed in
      the medial femoral condyle of healthy sheep. We observed that the presence of
      biomimetic hydroxyapatite on the pore's surface of the composite scaffold
      produces a better integration in the subchondral bone, in comparison to bare PLLA
      scaffolds.

PMID- 23152083
TI  - Body composition in subjects with anorexia nervosa: bioelectrical impedance
      analysis and dual-energy X-ray absorptiometry.
AB  - OBJECTIVE: To evaluate the applicability and validity of bioelectrical impedance
      analysis (BIA) compared with dual-energy X-ray absorptiometry (DXA) in a
      population of girls with restrictive anorexia nervosa (AN). METHODS: A total of
      30 girls (11-19 years old) with AN were enrolled. DXA and BIA (BIA software and
      the Deurenberg equations) were used to estimate the body composition. The
      correlation between the methods was assessed by Pearson's correlation coefficient
      and the Bland-Altman method. RESULTS: The mean FFM estimates were 33.2 kg (BIA
      software), 32.8 kg (BIA, Deurenberg equation) and 33.1 kg (DXA). The mean FM
      values were 5.6 kg (BIA software), 6.2 kg (BIA, Deurenberg equation) and 6.4 kg
      (DXA). There was a high correlation between the FFM values estimated with the two
      methods (BIA software vs DXA r=0.917, p<0.001; Deurenberg equation vs DXA
      r=0.931, p<0.001). For the FFM, the limits of agreement were equal to +/-3.34 kg
      for the BIA software and +/-2.96 kg for the Deurenberg equation. For the FM, the
      limits of agreement were equal to +/-4.60 kg for the BIA software and +/-3.82 kg
      for the Deurenberg equation. CONCLUSION: The results show a good correlation
      between DXA and BIA. BIA seems to be a valid alternative for epidemiological and
      clinical evaluations.

PMID- 23152084
TI  - Microvascular changes following four-hour single arteriole occlusion.
AB  - BACKGROUND: Free tissue transplantations are lengthy procedures that result in
      prolong tissue ischemia. Restoral of blood flow is essential for free flap
      recovery; however, upon reperfusion tissue that is viable may continue to be
      nonperfused. To further elucidate this pathophysiology skeletal muscle
      microcirculation was investigated during reperfusion following 4-hour single
      arteriole occlusion. MATERIALS AND METHODS: A blunt micropipette probe was use to
      compress a single arteriole in the unanesthetized hamster (N = 20) dorsal
      skinfold chamber. Arteriole (n = 20), capillary (n = 97), and postcapillary
      venule (n = 16) diameters and blood flow were analyzed at 0, 30, 60, 120, 240 min
      and 24 hours of reperfusion after 4 hour occlusion. RESULTS: Feeding arcade
      arterioles exhibited a brief (<10 min) vasoconstriction [0.31 +/- 0.26 (mean +/-
      SE) of baseline] upon reperfusion followed by a maximum vasodilation at 120 min
      (1.3 +/- 0.10: P < 0.05). Vasodilation was observed in transverse arterioles (A3)
      (1.8 +/- 0.20: P < 0.05). Correspondingly, all arteriole and venule flow was
      increased by 120 min (P < 0.05) of reperfusion. There was a transient decrease in
      the number of flowing capillaries at 0 and 30 min reperfusion (0.73 +/- 0.09 and
      0.84 +/- 0.06: P < 0.05, respectively). CONCLUSIONS: At the onset of reperfusion
      heterogeneous arteriole flow and transient decrease in flowing capillaries was
      observed; however, return of flow in all capillaries and an eventual hyperemic
      response in all arterioles suggests the reversible nature of this response.
      Single arteriole occlusion may allow for a more controlled and detailed
      microcirculatory analysis during ischemia-reperfusion.

PMID- 23152085
TI  - Triple DMARD combination for rheumatoid arthritis resistant to methotrexate and
      steroid combination: a single-center experience.
AB  - The mainstay of RA treatment is the disease-modifying antirheumatic drugs, and
      triple DMARD combination is now known to be better than monotherapies. Our aim in
      this trial was to report our clinical experience with triple DMARD therapy for
      resistant rheumatoid arthritis. Data of 140 patients with RA resistant to
      methotrexate and steroid combination were evaluated retrospectively. One hundred
      and nineteen (85 %) were female, and the median age at diagnosis was 56 (29-82)
      years. The median time between the diagnosis and beginning of triple therapy was
      45.5 (6-564) months. Fifty-two (37.1 %) patients (group 1) on triple therapy
      protocol achieved remission, but the others (88; 62.9 %) (group 2) did not. The
      mean DAS28 scores for the study group before triple DMARD therapy and after 12
      months under triple DMARD therapy were 4.93 and 3.24, respectively. The DAS28
      scores after 12 months for groups 1 and 2 were 2.57 and 3.64. The median follow
      up period for patients in group 1 was 60 months (23-118), and the mean DAS28
      score at the time of the analysis for group 1 was 2.36. Triple DMARD combination
      may save one-third of the MTX-resistant RA patients from the serious side effects
      and the cost of anti-TNF.

PMID- 23152086
TI  - No evidence for involvement of the toll-like receptor (TLR) 4 gene Asp299Gly and
      Thr399Ile polymorphisms in susceptibility to primary gouty arthritis.
AB  - Previous studies demonstrated that toll-like receptor (TLR) 4 was involved in the
      development of autoinflammatory disease including gouty arthritis (GA). TLR4
      functional gene Asp299Gly and Thr399Ile polymorphisms play a role in some
      autoinflammatory disease susceptibility. We undertook this study to analyze the
      association between the genetic polymorphisms within TLR4 gene and the
      susceptibility to GA in Chinese Han people. Two functional variants, Asp299Gly
      and Thr399Ile, in the TLR4 gene were genotyped using 5' exonuclease TaqMan
      technology from 218 male GA patients and 226 ethnically matched controls. None
      polymorphisms of Asp299Gly and Thr399Ile were detected in all GA cases and
      controls, which indicates that there is no evidence for involvement of the TLR4
      gene Asp299Gly and Thr399Ile polymorphisms in susceptibility to primary GA in the
      Chinese Han population. Further studies with extended single nucleotide
      polymorphisms should be performed.

PMID- 23152087
TI  - A primary analysis of sexual problems in Chinese patients with ankylosing
      spondylitis.
AB  - While the physical impact of ankylosing spondylitis (AS) is central to clinical
      treatment, the sexual problems associated with AS are often overlooked. Sexual
      problems may be related to a variety of undocumented demographic parameters,
      physical impairments, and psychological problems. These associations were
      examined through a single-center cross-sectional study of 103 AS patients (78
      males and 25 females) and 121 healthy individuals (73 males and 48 females). All
      participants provided information pertaining to sexual problems,
      sociodemographics, and clinical characteristics via written questionnaires
      including multiple-choice questions conducted independently in the clinical
      setting under physician supervision. Rates of both prevalence and severity of
      sexual dysfunctions in AS patients were much higher than those observed in
      healthy individuals. Bath Ankylosing Spondylitis (BAS) Disease Activity Index and
      two parameters of body image disturbance (distress and impairment in social
      functioning) correlated with impaired partner relationships (P < 0.05). BAS
      mobility index, impaired social functioning, and BAS functionality index were the
      most significant causes of impaired sexual function (P < 0.05) in AS patients.
      Both physical and psychological factors were shown to impact sexual relationships
      and function in Chinese AS patients. To more effectively manage AS in clinical
      settings, rheumatologists and nursing specialists should be aware of the
      condition's impact on sexual health, considering both physical outcomes, such as
      disease activity and physical function, as well as psychological well-being.

PMID- 23152088
TI  - The impact of Fibromyalgia on health-related quality of life in patients
      according to age.
AB  - Previous studies show controversial results regarding the influence of age on
      health-related quality of life (HRQOL) in patients with Fibromyalgia (FM). While
      some studies suggest that elderly patients have a worse HRQOL when compared with
      younger patients, others did not find differences according to age. The aim of
      the study was to analyse the impact of FM on HRQOL as far as patients' age is
      concerned. A cross-sectional study was conducted with 76 adult Portuguese women
      with FM between 22 and 75 years ([Formula: see text]; SD = 10.07). The HRQOL was
      assessed through the generic questionnaire Short-Form 36 Health Survey (SF-36).
      To this study, we considered the direct scores on each dimension that encompasses
      the SF-36, and standardized scores of each dimension by age and gender, using
      Portuguese normative data. Data regarding clinical and psychological variables
      (anxiety, depression and social support) were also collected. Of the total
      sample, 11 patients (14.5 %) had <39 years, 54 patients (71 %) had between 40 and
      59 years and 11 subjects (14.5 %) had 60 years or more. There were no differences
      between the three patient groups in any of the clinical and psychological
      variables considered, and the same lack of differences was observed in the SF-36
      direct scores. Nevertheless, when the analysis was made using the SF-36
      standardized scores, the patients over 60 years presented a significantly lower
      deterioration on physical (Physical Function, Role Physical and General Health)
      and social dimensions when compared with patients under 59 years, on Vitality
      when compared with patients under 39 years, and on Body Pain when compared to
      patients with age between 40 and 59 years. Regarding mental dimensions, no
      differences were found in the three age groups. In conclusion, it is important to
      control age effect on HRQOL to determine the specific impact of FM. Controlling
      the age effect on the HRQOL with standardized scores, elderly women with FM (>=60
      years) have less impact of the disease on the physical and social dimensions of
      the HRQOL than younger patients.

PMID- 23152089
TI  - Prognostic factors of sciatica in the Canon of Avicenna.
AB  - Prognosis studies are fast developing and very practical types of medical
      research. Sciatica is one of the common types of low back pain and identifying
      prognostic factors of the illness can help physicians and patients to choose best
      method of practice. The prognostic factors of sciatica are presented from the
      Canon of Avicenna, one of the most famous physicians in the history of medicine. 

PMID- 23152090
TI  - Differential effects of G- and F-actin on the plasma membrane calcium pump
      activity.
AB  - We have previously shown that plasma membrane calcium ATPase (PMCA) pump activity
      is affected by the membrane protein concentration (Vanagas et al., Biochim
      Biophys Acta 1768:1641-1644, 2007). The results of this study provided evidence
      for the involvement of the actin cytoskeleton. In this study, we explored the
      relationship between the polymerization state of actin and its effects on
      purified PMCA activity. Our results show that PMCA associates with the actin
      cytoskeleton and this interaction causes a modulation of the catalytic activity
      involving the phosphorylated intermediate of the pump. The state of actin
      polymerization determines whether it acts as an activator or an inhibitor of the
      pump: G-actin and/or short oligomers activate the pump, while F-actin inhibits
      it. The effects of actin on PMCA are the consequence of direct interaction as
      demonstrated by immunoblotting and cosedimentation experiments. Taken together,
      these findings suggest that interactions with actin play a dynamic role in the
      regulation of PMCA-mediated Ca(2+) extrusion through the membrane. Our results
      provide further evidence of the activation-inhibition phenomenon as a property of
      many cytoskeleton-associated membrane proteins where the cytoskeleton is no
      longer restricted to a mechanical function but is dynamically involved in
      modulating the activity of integral proteins with which it interacts.

PMID- 23152091
TI  - Modulation of chitotriosidase during macrophage differentiation.
AB  - Macrophages as a principal component of immune system play an important role in
      the initiation, modulation, and final activation of the immune response against
      pathogens. Upon stimulation with different cytokines, macrophages can undergo
      classical or alternative activation to become M1 or M2 macrophages, which have
      different functions during infections. Although chitotriosidase is widely
      accepted as a marker of activated macrophages and is thought to participate in
      innate immunity, particularly in defense mechanisms against chitin containing
      pathogens, little is known about its expression during macrophages full
      maturation and polarization. In this study we analyzed CHIT-1 modulation during
      monocyte-to-macrophage maturation and during their polarization. The levels of
      CHIT-1 expression was investigated in human monocytes obtained from buffy coat of
      healthy volunteers, polarized to classically activated macrophages (or M1), whose
      prototypical activating stimuli are interferon-gamma and lipopolysaccharide, and
      alternatively activated macrophages (or M2) obtained by interleukin-4 exposure by
      real-time PCR and by Western blot analysis. During monocyte-macrophage
      differentiation both protein synthesis and mRNA analysis showed that CHIT-1 rises
      significantly and is modulated in M1 and M2 macrophages.Our results demonstrated
      that variations of CHIT-1 production are strikingly associated with macrophages
      polarization, indicating a different rule of this enzyme in the specialized
      macrophages.

PMID- 23152092
TI  - A higher alkaline dietary load is associated with greater indexes of skeletal
      muscle mass in women.
AB  - Conservation of muscle mass is important for fall and fracture prevention but
      further understanding of the causes of age-related muscle loss is required. This
      study found a more alkaline diet was positively associated with muscle mass in
      women suggesting a role for dietary acid-base load in muscle loss. INTRODUCTION:
      Conservation of skeletal muscle is important for preventing falls and fractures
      but age-related loss of muscle mass occurs even in healthy individuals. However,
      the mild metabolic acidosis associated with an acidogenic dietary acid-base load
      could influence loss of muscle mass. METHODS: We investigated the association
      between fat-free mass (FFM), percentage FFM (FFM%) and fat-free mass index (FFMI,
      weight/height2), measured using dual-energy X-ray absorptiometry in 2,689 women
      aged 18-79 years from the TwinsUK Study, and dietary acid-base load. Body
      composition was calculated according to quartile of potential renal acid load and
      adjusted for age, physical activity, misreporting and smoking habit (FFM, FFMI
      also for fat mass) and additionally with percentage protein. RESULTS: Fat-free
      mass was positively associated with a more alkalinogenic dietary load (comparing
      quartile 1 vs 4: FFM 0.79 kg P < 0.001, FFM% 1.06 % <0.001, FFMI 0.24 kg/m2 P =
      0.002), and with the ratio of fruits and vegetables to potential acidogenic
      foods. CONCLUSIONS: We observed a small but significant positive association
      between a more alkaline diet and muscle mass indexes in healthy women that was
      independent of age, physical activity and protein intake equating to a scale of
      effect between a fifth and one half of the observed relationship with 10 years of
      age. Although protein is important for maintenance of muscle mass, eating fruits
      and vegetables that supply adequate amounts of potassium and magnesium are also
      relevant. The results suggest a potential role for diet in the prevention of
      muscle loss.

PMID- 23152093
TI  - Bisphosphonates reduced the risk of acute myocardial infarction: a 2-year follow
      up study.
AB  - This population-based matched cohort analysis explored the effects of
      bisphosphonate treatment on acute myocardial infarction (AMI). We found that
      patients who received bisphosphonate therapy had a lower risk of AMI during a 2
      year follow-up period (hazard ratio (HR) = 0.35). Our data support that
      bisphosphonates may provide protective effects against cardiovascular events.
      INTRODUCTION: Although bisphosphonates have been suggested to have anti
      atherosclerotic effects in animal models, evidence in human subjects is still
      conflicting. Therefore, this study aimed to explore the effects of bisphosphonate
      treatment on AMI using a population-based cohort study. METHODS: We identified
      1,548 patients who received bisphosphonate therapy for osteoporotic fractures and
      randomly extracted 4,644 subjects with vertebral or hip fractures as a comparison
      cohort. Each patient was individually tracked for 2 years to identify those who
      subsequently suffered an AMI. Stratified Cox proportional hazards regressions
      were performed to assess the effect of bisphosphonate treatment on the risk of
      AMI. RESULTS: Six (0.4 %) of the patients who received bisphosphonate therapy and
      49 (1.1 %) of the comparison subjects suffered an AMI during the 2-year follow-up
      period. The incidence rate of AMI was 1.94 (95 % CI = 0.79-4.03) per 1,000 person
      years in patients who received bisphosphonate therapy and 5.28 (95 % CI = 3.95
      6.92) per 1,000 person-years in comparison patients. Regression analysis revealed
      that patients who received bisphosphonate therapy had a lower hazard of AMI
      during the 2-year follow-up period than comparison patients (HR = 0.37, 95 % CI =
      0.16-0.85, p = 0.020). After censoring cases that died from non-AMI causes and
      adjusting for both demographic and risk factors, the HR of AMI for patients who
      received bisphosphonate therapy was 0.35 (95 % CI = 0.14-0.84, p = 0.020) than
      that of comparison patients. CONCLUSIONS: Patients who received bisphosphonate
      therapy had a lower risk of AMI during the 2-year follow-up period. Our data
      support that bisphosphonates may provide protective effects against
      cardiovascular events.

PMID- 23152095
TI  - Time trends for alendronate prescription practices in women with chronic
      obstructive pulmonary disease and women exposed to systemic glucocorticoids.
AB  - Chronic obstructive pulmonary disease (COPD) and systemic glucocorticoid exposure
      are well-known risk factors of osteoporosis. We evaluated alendronate
      prescription practices related to COPD and exposure to systemic corticosteroids
      from 1996 to 2008 and showed an increasing targeting of alendronate treatment in
      patients with COPD and patients with systemic corticosteroid exposure.
      INTRODUCTION: COPD and systemic glucocorticoid exposure are well-known risk
      factors of osteoporosis and fragility fracture, but osteoporosis is often
      underdiagnosed and undertreated in these patients. This study aims to evaluate
      alendronate prescription practices related to COPD and/or to exposure to systemic
      glucocorticoids among Danish women. METHODS: A total of 388,314 female subjects
      >50 years old, 64,719 of whom initiated treatment with alendronate, and 323,595
      age- and gender-matched controls were retrospectively identified between 1996 and
      2008 from national health registers. Multivariate logistic regression was used
      for examining prescription practices, specifically if these risk factors (COPD or
      glucocorticoid exposure) increased or decreased the likelihood of beginning
      alendronate therapy. RESULTS: A diagnosis of COPD was associated with an
      increased likelihood of using alendronate (odds ratio (OR) 1.4, 95 % confidence
      interval (CI) 1.4-1.5, p < 0.001). Further, a diagnosis of COPD was associated
      with an increasing tendency of initiating alendronate treatment in the study
      period (OR 1.3 (95 % CI 1.1-1.5, years 1996-1999) to 1.5 (95 % CI 1.4-1.6, years
      2006-2008), p < 0.01). Exposure to systemic glucocorticoids was associated with a
      significantly increasing (OR 3.6, 95 % CI 3.3-3.9 to OR 5.5, 95 % CI 5.3-5.8)
      probability of receiving alendronate treatment in the same observation period.
      CONCLUSION: This nationwide register-based study on alendronate prescription
      practices in Denmark shows an increasing targeting of alendronate treatment in
      patients with COPD and an even stronger trend for patients with systemic
      glucocorticoid exposure, perhaps indicating increased awareness of well-known and
      associated conditions.

PMID- 23152096
TI  - Kounis syndrome secondary to simultaneous oral amoxicillin and parenteral
      ampicillin use in a young man.
AB  - The concurrence of acute coronary syndrome with allergy or hypersensitivity as
      well as with anaphylactic or anaphylactoid reactions is increasingly encountered
      in daily clinical practice. There are several reports associating mast cell
      activation with acute cardiovascular events in adults. This was first described
      by Kounis as 'allergic angina syndrome',progressing to 'allergic myocardial
      infarction'. The main mechanism proposed is the vasospasm of coronary arteries.
      We present a case of a 28-year-old man who was admitted to our hospital with
      thoracic pain and dyspnoea. The symptoms recurred after simultaneous use of 1 g
      amoxicillin/clavulanic acid orally and 1 g ampicillin/sulbactam parenterally for
      tonsillitis the night before presentation and on the morning of admission.

PMID- 23152097
TI  - Synthesis of colloidal metal and metal alloy nanoparticles for electrochemical
      energy applications.
AB  - This Review is focused on the recent progresses in the synthetic approaches to
      the precise control of structure, size, shape, composition and multi
      functionality of metal and metal alloy nanoparticles. Many of these strategies
      have been developed based on colloidal methods, and to limited extent, the
      galvanic and other methods. The shape, size and composition often govern the
      chemical and catalytic properties that are important for electrochemical energy
      applications. The structure-property relationship and the design in controllable
      structures and morphologies for specific reactions such as oxygen reduction
      reaction (ORR) are emphasized.

PMID- 23152094
TI  - Skeletal effects of nutrients and nutraceuticals, beyond calcium and vitamin D.
AB  - There is a need to understand the role of nutrition, beyond calcium and vitamin
      D, in the treatment and prevention of osteoporosis in adults. Results regarding
      soy compounds on bone density and bone turnover are inconclusive perhaps due to
      differences in dose and composition or in study population characteristics. The
      skeletal benefit of black cohosh and red clover are unknown.
      Dehydroepiandrosterone (DHEA) use may benefit elderly individuals with low serum
      dehydroepiandrosterone-sulfate levels, but even in this group, there are
      inconsistent benefits to bone density (BMD). Higher fruit and vegetable intakes
      may relate to higher BMD. The skeletal benefit of flavonoids, carotenoids, omega
      3-fatty acids, and vitamins A, C, E and K are limited to observational data or a
      few clinical trials, in some cases investigating pharmacologic doses. Given
      limited data, it would be better to get these nutrients from fruits and
      vegetables. Potassium bicarbonate may improve calcium homeostasis but with little
      impact on bone loss. High homocysteine may relate to fracture risk, but the
      skeletal benefit of each B vitamin is unclear. Magnesium supplementation is
      likely only required in persons with low magnesium levels. Data are very limited
      for the role of nutritional levels of boron, strontium, silicon and phosphorus in
      bone health. A nutrient rich diet with adequate fruits and vegetables will
      generally meet skeletal needs in healthy individuals. For most healthy adults,
      supplementation with nutrients other than calcium and vitamin D may not be
      required, except in those with chronic disease and the frail elderly.

PMID- 23152098
TI  - Impact of tobacco control policy on quitting and nicotine dependence among women
      in five European countries.
AB  - OBJECTIVE: To describe differences in and factors associated with former smoking
      and nicotine dependence among women in Ireland, Sweden, France, Italy and the
      Czech Republic. METHODS: A cross-sectional, random digit dial telephone survey of
      5000 women, aged 18 years and older, conducted in 2008. Analyses were conducted
      using logistic regression models. RESULTS: Respondents from Ireland and Sweden
      had statistically significantly higher odds of having quit smoking within the 5
      years before survey administration compared with respondents from the Czech
      Republic. Current smokers from Ireland, Sweden, France and Italy are more
      nicotine dependent than those from the Czech Republic. CONCLUSIONS: Respondents
      from countries with stronger tobacco control policies were more likely to have
      quit smoking compared with those living in the Czech Republic. However,
      respondents in countries with some of the strongest policies (Ireland, Sweden,
      France and Italy) had higher odds of smoking within 30 min of waking, an
      established indicator of nicotine dependence. More research in this area is
      warranted, but this study suggests that now that the Czech Republic is beginning
      to implement strong tobacco control policy, they will probably achieve a rapid
      decline in population-level smoking. Ireland, Sweden, France, Italy and other
      countries with established, strong tobacco control policies would do well to
      consider what additional programmes they can put in place to help their highly
      nicotine-dependent population of smokers successfully quit.

PMID- 23152099
TI  - Creating demand for foreign brands in a 'home run' market: tobacco company
      tactics in South Korea following market liberalisation.
AB  - OBJECTIVE: To analyse the tactics transnational tobacco companies (TTCs) used to
      increase market share in South Korea after market liberalisation in 1988, and the
      subsequent impact of TTCs' activities on the domestic industry and ultimately
      public health. METHODS: Internal tobacco industry documents were searched
      iteratively and analysed by keyword related to strategies for increasing market
      share in Korea since liberalisation. RESULTS: Following market liberalisation,
      TTCs faced entrenched cultural and institutional barriers in Korea which hindered
      increased sales of cigarette imports. TTCs identified population groups more
      favourably inclined towards imported brands, developed new distribution channels
      and used promotional activities targeting these groups. The growth in market
      share by TTCs suggests that these activities were successful at challenging the
      Korea Tobacco & Ginseng Corporation (KTGC) monopoly. In response, KTGC shifted to
      a proactive marketing approach and adopted strategies similar to TTCs. This, in
      turn, made the Korean market highly competitive. Findings show that, after market
      liberalisation, there was an upward trend in cigarette consumption and smoking
      prevalence among the targeted population groups, notably youth and young women.
      CONCLUSIONS: Governments engaging in trade negotiations that may lead to the
      opening of domestic tobacco markets need a fuller understanding of previous
      industry activities for expanding into emerging markets as well as how the
      domestic industry can change accordingly. To protect public health, the adoption
      of comprehensive tobacco control measures, guided by WHO Framework Convention on
      Tobacco Control, are needed as part of such negotiations.

PMID- 23152100
TI  - The importance of cigarette packaging in a 'dark' market: the 'Silk Cut'
      experience.
AB  - In a growing number of countries tobacco companies are severely restricted in how
      they can legally market their products. In these 'dark' markets the role of
      packaging as a promotional and communications tool becomes more pronounced. How
      packaging is used for the most expensive cigarette brands in dark markets has
      received limited attention however, even though these 'premium' cigarette brands
      significantly impact upon the profitability of tobacco companies. We outline,
      using retail trade press journals, how packaging was used for premium brand 'Silk
      Cut' in the UK from 2004 to 2011, following a comprehensive ban on tobacco
      advertising, promotions and sponsorship. From 2004 to 2008 packaging was used to
      help launch two new variants and during this period Silk Cut market share of the
      premium sector grew by 1.1%. Overall share of the cigarette market for the Silk
      Cut house (brand family) fell however due to the continuing decline of the
      premium sector. From 2008 to 2011 changes to the packaging were much more
      frequent, including the repeated use of limited-edition designs, and
      modifications to pack shape, texture, style of opening, cellophane, foil and
      inner frame. Silk Cut's share of the premium sector grew a further 2.9% from 2008
      to 2011, and overall cigarette market share increased. That a premium brand can
      report any level of growth within such a hostile market, where most advertising,
      promotion and sponsorship is banned, taxation is among the highest in the world,
      and in the midst of a recession, is testament to the value of packaging. 

PMID- 23152101
TI  - The 'diverse, dynamic new world of global tobacco control'? An analysis of
      participation in the Conference of the Parties to the WHO Framework Convention on
      Tobacco Control.
AB  - INTRODUCTION: The increasingly inequitable impacts of tobacco use highlight the
      importance of ensuring developing countries' ongoing participation in global
      tobacco control. The WHO Framework Convention on Tobacco Control (FCTC) has been
      widely regarded as reflecting the high engagement and effective influence of
      developing countries. METHODS: We examined participation in FCTC governance based
      on records from the first four meetings of the Conference of the Parties (COP),
      comparing representation and delegate diversity across income levels and WHO
      regions. RESULTS: While attendance at the COP sessions is high, there are
      substantial disparities in the relative representation of different income levels
      and regions, with lower middle and low income countries contributing only 18% and
      10% of total meeting delegates, respectively. In regional terms, Europe provided
      the single largest share of delegates at all except the Durban (2008) meeting.
      Thirty-nine percent of low income countries and 27% of those from Africa were
      only ever represented by a single person delegation compared with 10% for high
      income countries and 11% for Europe. Rotation of the COP meeting location outside
      of Europe is associated with better representation of other regions and a
      stronger presence of delegates from national ministries of health and focal
      points for tobacco control. CONCLUSIONS: Developing countries face particular
      barriers to participating in the COP process, and their engagement in global
      tobacco control is likely to diminish in the absence of specific measures to
      support their effective participation.

PMID- 23152102
TI  - Closed-loop control of zebrafish response using a bioinspired robotic-fish in a
      preference test.
AB  - In this paper, we study the response of zebrafish to a robotic-fish whose
      morphology and colour pattern are inspired by zebrafish. Experiments are
      conducted in a three-chambered instrumented water tank where a robotic-fish is
      juxtaposed with an empty compartment, and the preference of live subjects is
      scored as the mean time spent in the vicinity of the tank's two lateral sides.
      The tail-beating of the robotic-fish is controlled in real-time based on feedback
      from fish motion to explore a spectrum of closed-loop systems, including
      proportional and integral controllers. Closed-loop control systems are
      complemented by open-loop strategies, wherein the tail-beat of the robotic-fish
      is independent of the fish motion. The preference space and the locomotory
      patterns of fish for each experimental condition are analysed and compared to
      understand the influence of real-time closed-loop control on zebrafish response.
      The results of this study show that zebrafish respond differently to the pattern
      of tail-beating motion executed by the robotic-fish. Specifically, the preference
      and behaviour of zebrafish depend on whether the robotic-fish tail-beating
      frequency is controlled as a function of fish motion and how such closed-loop
      control is implemented.

PMID- 23152103
TI  - A modular versatile chip carrier for high-throughput screening of cell
      biomaterial interactions.
AB  - The field of biomaterials research is witnessing a steady rise in high-throughput
      screening approaches, comprising arrays of materials of different physico
      chemical composition in a chip format. Even though the cell arrays provide many
      benefits in terms of throughput, they also bring new challenges. One of them is
      the establishment of robust homogeneous cell seeding techniques and strong
      control over cell culture, especially for long time periods. To meet these
      demands, seeding cells with low variation per tester area is required, in
      addition to robust cell culture parameters. In this study, we describe the
      development of a modular chip carrier which represents an important step in
      standardizing cell seeding and cell culture conditions in array formats. Our
      carrier allows flexible and controlled cell seeding and subsequent cell culture
      using dynamic perfusion. To demonstrate the application of our device, we
      successfully cultured and evaluated C2C12 premyoblast cell viability under
      dynamic conditions for a period of 5 days using an automated pipeline for image
      acquisition and analysis. In addition, using computational fluid dynamics,
      lactate and BMP-2 as model molecules, we estimated that there is good exchange of
      nutrients and metabolites with the flowing medium, whereas no cross-talk between
      adjacent TestUnits should be expected. Moreover, the shear stresses to the cells
      can be tailored uniformly over the entire chip area. Based on these findings, we
      believe our chip carrier may be a versatile tool for high-throughput cell
      experiments in biomaterials sciences.

PMID- 23152104
TI  - Implications of spatially heterogeneous vaccination coverage for the risk of
      congenital rubella syndrome in South Africa.
AB  - Rubella is generally a mild childhood disease, but infection during early
      pregnancy may cause spontaneous abortion or congenital rubella syndrome (CRS),
      which may entail a variety of birth defects. Since vaccination at levels short of
      those necessary to achieve eradication may increase the average age of infection,
      and thus potentially the CRS burden, introduction of the vaccine has been limited
      to contexts where coverage is high. Recent work suggests that spatial
      heterogeneity in coverage should also be a focus of concern. Here, we use a
      detailed dataset from South Africa to explore the implications of heterogeneous
      vaccination for the burden of CRS, introducing realistic vaccination scenarios
      based on reported levels of measles vaccine coverage. Our results highlight the
      potential impact of country-wide reductions of incidence of rubella on the local
      CRS burdens in districts with small population sizes. However, simulations
      indicate that if rubella vaccination is introduced with coverage reflecting
      current estimates for measles coverage in South Africa, the burden of CRS is
      likely to be reduced overall over a 30 year time horizon by a factor of 3,
      despite the fact that this coverage is lower than the traditional 80 per cent
      rule of thumb for vaccine introduction, probably owing to a combination of
      relatively low birth and transmission rates. We conclude by discussing the likely
      impact of private-sector vaccination.

PMID- 23152105
TI  - The workings of the maximum entropy principle in collective human behaviour.
AB  - We present an exhaustive study of the rank-distribution of city-population and
      population-dynamics of the 50 Spanish provinces (more than 8000 municipalities)
      in a time-window of 15 years (1996-2010). We exhibit compelling evidence
      regarding how well the MaxEnt principle describes the equilibrium distributions.
      We show that the microscopic dynamics that governs population growth is the
      deciding factor that originates the observed macroscopic distributions. The
      connection between microscopic dynamics and macroscopic distributions is
      unravelled via MaxEnt.

PMID- 23152106
TI  - Computational modelling of T-cell formation kinetics: output regulated by initial
      proliferation-linked deferral of developmental competence.
AB  - Bone-marrow-derived progenitors must continually enter the thymus of an adult
      mouse to sustain T-cell homeostasis, yet only a few input cells per day are
      sufficient to support a yield of 5 * 10(7) immature T-cells per day and an
      eventual output of 1-2 * 10(6) mature cells per day. While substantial progress
      has been made to delineate the developmental pathway of T-cell lineage
      commitment, still little is known about the relationship between differentiation
      competence and the remarkable expansion of the earliest (DN1 stage) T-cell
      progenitors. To address this question, we developed computational models where
      the probability to progress to the next stage (DN2) is related to division
      number. To satisfy differentiation kinetics and overall cell yield data, our
      models require that adult DN1 cells divide multiple times before becoming
      competent to progress into DN2 stage. Our findings were subsequently tested by in
      vitro experiments, where putative early and later-stage DN1 progenitors from the
      thymus were purified and their progression into DN2 was measured. These
      experiments showed that the two DN1 sub-populations divided with similar rates,
      but progressed to the DN2 stage with different rates, thus providing experimental
      evidence that DN1 cells increase their commitment probability in a cell-intrinsic
      manner as they undergo cell division. Proliferation-linked shifts in eligibility
      of DN1 cells to undergo specification thus control kinetics of T-cell generation.

PMID- 23152107
TI  - Antiproliferative effects of kisspeptin-10 depend on artificial GPR54 (KISS1R)
      expression levels.
AB  - Kisspeptins are peptides derived from the metastasis suppressor gene KISS1
      interacting with GPR54 as their corresponding receptor. The KISS1/GPR54 system is
      one regulator of cellular motility mechanisms leading to decreased migration and
      invasion. Its role in cell proliferation processes is not clearly understood. In
      this study, breast cancer cell lines, T47D, ZR75-1, MDA-MB-231, MDA-MB-435s, MDA
      MB-453, HCC 70, HCC 1806, HCC 1937 and MCF-7, were investigated for their
      endogenous GPR54 expression by immunocytochemistry, RT-PCR and western blot
      analysis. The effect of kisspeptin-10 on proliferation was measured in MDA-MB
      231, MDA-MB-435s, HCC 1806 and MCF-7 cells. Further experiments on proliferation
      were carried out with cells transfected with GPR54. All of the tested breast
      cancer cell lines expressed GPR54 in different amounts. No effects on
      proliferation were detected in the breast cancer cells expressing the receptor
      endogenously. In transfected neuronal cells overexpressing GPR54, proliferation
      was significantly inhibited by kisspeptin-10. The results indicate that the
      antiproliferative action of kisspeptin depends on the nature of GPR54 expression.
      The effect was detected in an artificial system of cells transfected with GPR54
      and not in cells expressing the receptor endogenously. Thus, the
      antiproliferative action of kisspeptin seems not to be important for
      pathophysiological processes.

PMID- 23152108
TI  - Seasonal restructuring of the ground squirrel gut microbiota over the annual
      hibernation cycle.
AB  - Many hibernating mammals suspend food intake during winter, relying solely on
      stored lipids to fuel metabolism. Winter fasting in these species eliminates a
      major source of degradable substrates to support growth of gut microbes, which
      may affect microbial community structure and host-microbial interactions. We
      explored the effect of the annual hibernation cycle on gut microbiotas using deep
      sequencing of 16S rRNA genes from ground squirrel cecal contents. Squirrel
      microbiotas were dominated by members of the phyla Bacteroidetes, Firmicutes, and
      Verrucomicrobia. UniFrac analysis showed that microbiotas clustered strongly by
      season, and maternal influences, diet history, host age, and host body
      temperature had minimal effects. Phylogenetic diversity and numbers of
      operational taxonomic units were lowest in late winter and highest in the spring
      after a 2-wk period of refeeding. Hibernation increased relative abundance of
      Bacteroidetes and Verrucomicrobia, phyla that contain species capable of
      surviving on host-derived substrates such as mucins, and reduced relative
      abundance of Firmicutes, many of which prefer dietary polysaccharides.
      Hibernation reduced cecal short-chain fatty acid and ammonia concentrations, and
      increased and decreased concentrations of acetate and butyrate, respectively.
      These results indicate that the ground squirrel microbiota is restructured each
      year in a manner that reflects differences in microbial preferences for dietary
      vs. host-derived substrates, and thus the competitive abilities of different taxa
      to survive in the altered environment in the hibernator gut.

PMID- 23152109
TI  - Role of the transient receptor potential vanilloid type 1 channel in renal
      inflammation induced by lipopolysaccharide in mice.
AB  - To determine the role of the transient receptor potential vanilloid type 1
      (TRPV1) channel in the regulation of renal inflammation, lipopolysaccharide (LPS,
      3 mg/kg) was intraperitoneally injected into wild-type (WT) and TRPV1-null mutant
      (TRPV1(-/-)) mice. The kidney and serum were collected 6 or 24 h after LPS
      injection for morphological analysis and proinflammatory cytokine assay. LPS
      injection led to a similar degree of transient hypotension and bradycardia in WT
      and TRPV1(-/-) mice determined by a telemetry system. LPS administration caused
      parenchymal red blood cell congestion and fading of intact glomerular structure
      in TRPV1(-/-) compared with WT mice. Serum creatinine levels were higher 24 h
      after LPS injection in TRPV1(-/-) than in WT mice. Neutrophil and macrophage
      infiltration in the kidneys was greater 6 h for the former and 24 h for both
      after LPS injection in TRPV1(-/-) than in WT mice. Serum cytokine levels
      including tumor necrosis factor (TNF)-alpha, IL-1beta, and IL-6 were higher 6 h
      after LPS injection in TRPV1(-/-) compared with WT mice. Likewise, renal
      chemokine levels including keratinocyte-derived chemokines and macrophage
      inflammatory protein were higher 6 h after LPS injection in TRPV1(-/-) than in WT
      mice. Renal VCAM-1 and ICAM-1 expression was further elevated 6 h for the former
      and 24 h for the latter after LPS injection in TRPV1(-/-) than in WT mice. Renal
      nuclear factor-kappaB (NF-kappaB) activity was further increased 6 h after LPS
      injection in TRPV1(-/-) compared with WT mice. Pharmacological blockade TRPV1 in
      WT mice showed aggravated renal and serum inflammatory responses resembling that
      of TRPV1(-/-) mice. Thus TRPV1 gene ablation exacerbates LPS-induced renal tissue
      and function injury, including aggravated renal neutrophil and macrophage
      infiltration, chemokine and adhesion molecule levels, and glomerular
      hypercellularity accompanying with further increased serum creatinine and
      cytokine levels. These results indicate that TRPV1 is activated during LPS
      challenge, which may constitute a protect mechanism against LPS-induced renal
      injury via reducing renal inflammatory responses.

PMID- 23152110
TI  - Effect of chronic perinatal hypoxia on the role of rho-kinase in pulmonary artery
      contraction in newborn lambs.
AB  - Exposure to chronic hypoxia during gestation predisposes infants to neonatal
      pulmonary hypertension, but the underlying mechanisms remain unclear. Here, we
      test the hypothesis that moderate continuous hypoxia during gestation causes
      changes in the rho-kinase pathway that persist in the newborn period, altering
      vessel tone and responsiveness. Lambs kept at 3,801 m above sea level during
      gestation and the first 2 wk of life were compared with those with gestation at
      low altitude. In vitro studies of isolated pulmonary arterial rings found a more
      forceful contraction in response to KCl and 5-HT in high-altitude compared with
      low-altitude lambs. There was no difference between the effects of blockers of
      various pathways of extracellular Ca(2+) entry in low- and high-altitude
      arteries. In contrast, inhibition of rho-kinase resulted in significantly greater
      attenuation of 5-HT constriction in high-altitude compared with low-altitude
      arteries. High-altitude lambs had higher baseline pulmonary artery pressures and
      greater elevations in pulmonary artery pressure during 15 min of acute hypoxia
      compared with low-altitude lambs. Despite evidence for an increased role for rho
      kinase in high-altitude arteries, in vivo studies found no significant difference
      between the effects of rho-kinase inhibition on hypoxic pulmonary
      vasoconstriction in intact high-altitude and low-altitude lambs. We conclude that
      chronic hypoxia in utero results in increased vasopressor response to both acute
      hypoxia and serotonin, but that rho-kinase is involved only in the increased
      response to serotonin.

PMID- 23152111
TI  - Increasing temperature speeds intracellular PO2 kinetics during contractions in
      single Xenopus skeletal muscle fibers.
AB  - Precise determination of the effect of muscle temperature (T(m)) on mitochondrial
      oxygen consumption kinetics has proven difficult in humans, in part due to the
      complexities in controlling for T(m)-related variations in blood flow, fiber
      recruitment, muscle metabolism, and contractile properties. To address this
      issue, intracellular Po(2) (P(i)(O(2))) was measured continuously by
      phosphorescence quenching following the onset of contractions in single Xenopus
      myofibers (n = 24) while controlling extracellular temperature. Fibers were
      subjected to two identical contraction bouts, in random order, at 15 degrees C
      (cold, C) and 20 degrees C (normal, N; n = 12), or at N and 25 degrees C (hot, H;
      n = 12). Contractile properties were determined for every contraction. The time
      delay of the P(i)(O(2)) response was significantly greater in C (59 +/- 35 s)
      compared with N (35 +/- 26 s, P = 0.01) and H (27 +/- 14 s, P = 0.01). The time
      constant for the decline in P(i)(O(2)) was significantly greater in C (89 +/- 34
      s) compared with N (52 +/- 15 s; P < 0.01) and H (37 +/- 10 s; P < 0.01). There
      was a linear relationship between the rate constant for P(i)(O(2)) kinetics and
      T(m) (r = 0.322, P = 0.03). Estimated ATP turnover was significantly greater in H
      than in C (P < 0.01), but this increased energy requirement alone with increased
      T(m) could not account for the differences observed in P(i)(O(2)) kinetics among
      conditions. These results demonstrate that P(i)(O(2)) kinetics in single
      contracting myofibers are dependent on T(m), likely caused by temperature-induced
      differences in metabolic demand and by temperature-dependent processes underlying
      mitochondrial activation at the start of muscle contractions.

PMID- 23152112
TI  - Differential expression of the pro-natriuretic peptide convertases corin and
      furin in experimental heart failure and atrial fibrosis.
AB  - In heart failure (HF), the cardiac hormone natriuretic peptides (NPs) atrial
      (ANP), B-type (BNP), and C-type (CNP) play a key role to protect cardiac
      remodeling. The proprotein convertases corin and furin process their respective
      pro-NPs into active NPs. Here we define in a canine model of HF furin and corin
      gene and protein expression in normal and failing left atrium (LA) or ventricle
      (LV) testing the hypothesis that the NP proproteins convertases production is
      altered in experimental HF. Experimental canine HF was produced by rapid right
      ventricular pacing for 10 days. NPs, furin, and corin mRNA expression were
      determined by quantitative RT-PCR. Protein concentration or expression was
      determined by immunostaining, radioimmunoassay, or Western blot. Furin and corin
      proteins were present in normal canine LA and LV myocardium and vasculature and
      in smooth muscle cells. In normal canines, expression of NPs was dominant in the
      atrium compared with the ventricle. In experimental early stage HF characterized
      with marked atrial fibrosis, ANP, BNP, and CNP mRNA, and protein concentrations
      were higher in HF LA but not HF LV compared with normals. In LA, corin mRNA and
      protein expressions in HF were lower, whereas furin mRNA and protein expressions
      were higher than normals. NPs and furin expressions were augmented in the atrium
      in experimental early stage HF and, conversely, corin mRNA and protein
      expressions were decreased with atrial remodeling. Selective changes of these NP
      convertases may have significance in the regulation of pro-NP processing and
      atrial remodeling in early stage HF.

PMID- 23152113
TI  - Restoration of renal function by a novel prostaglandin EP4 receptor-derived
      peptide in models of acute renal failure.
AB  - Acute renal failure (ARF) is a serious medical complication characterized by an
      abrupt and sustained decline in renal function. Despite significant advances in
      supportive care, there is currently no effective treatment to restore renal
      function. PGE(2) is a lipid hormone mediator abundantly produced in the kidney,
      where it acts locally to regulate renal function; several studies suggest that
      modulating EP(4) receptor activity could improve renal function following kidney
      injury. An optimized peptidomimetic ligand of EP(4) receptor, THG213.29, was
      tested for its efficacy to improve renal function (glomerular filtration rate,
      renal plasma flow, and urine output) and histological changes in a model of ARF
      induced by either cisplatin or renal artery occlusion in Sprague-Dawley rats.
      THG213.29 modulated PGE(2)-binding dissociation kinetics, indicative of an
      allosteric binding mode. Consistently, THG213.29 antagonized EP(4)-mediated
      relaxation of piglet saphenous vein rings, partially inhibited EP(4)-mediated
      cAMP production, but did not affect Galpha(i) activation or beta-arrestin
      recruitment. In vivo, THG213.29 significantly improved renal function and
      histological changes in cisplatin- and renal artery occlusion-induced ARF models.
      THG213.29 increased mRNA expression of heme-oxygenase 1, Bcl2, and FGF-2 in renal
      cortex; correspondingly, in EP(4)-transfected HEK293 cells, THG213.29 augmented
      FGF-2 and abrogated EP(4)-dependent overexpression of inflammatory IL-6 and of
      apoptotic death domain-associated protein and BCL2-associated agonist of cell
      death. Our results demonstrate that THG213.29 represents a novel class of
      diuretic agent with noncompetitive allosteric modulator effects on EP(4)
      receptor, resulting in improved renal function and integrity following acute
      renal failure.

PMID- 23152115
TI  - Single-incision laparoscopic adjustable gastric banding is effective and safe:
      756 cases in an academic medical center.
AB  - BACKGROUND: Laparoscopic adjustable gastric banding (LAGB) is safe and effective.
      This less invasive option involving fewer incisions and umbilical approaches is
      coined as single-incision laparoscopic surgery (SILS). Over the last 3 years, we
      performed 46 % of our LAGBs as SILS with excellent results. METHODS: This is a
      retrospective review of 1,644 LAGBs performed between 2008 and 2010. A total of
      756 were performed as SILS bands (46 %) and 888 as standard (non-SILS) (54 %).
      Data points compared include operative time, percent of excess weight loss at 1
      and 2 years, complication, and re-operation rates. RESULTS: Groups were matched
      by age, initial BMI, and gender: 584 non-SILS and 710 SILS patients. The average
      operating time was 44.3 +/- 19.6 min for SILS and 51.1 +/- 19.4 min for non-SILS
      (p < 0.001). The 12-month percent excess weight loss (%EWL) for SILS was 45.0 +/-
      19.1; it was 40.7 +/- 17.5 for non-SILS (p = 0.003). The 24 month %EWL for SILS
      was 54.4 +/- 16.3; it was 46.4 +/- 16.1 for non-SILS (p = 0.10). Complication
      rates were 5.6 % (40 of 710) for SILS and 4.5 % (26 of 584) for non-SILS (p =
      0.34). The 30-day readmission/re-operation rates are 1 % (seven of 710) for SILS
      and 1.5 % (nine of 584) for non-SILS (p = 0.37). There was one death in the SILS
      group. CONCLUSIONS: We have been performing more SILS bands over time. Our
      operative times and weight loss figures show that it is an efficient and
      effective means of weight loss. Furthermore, the data also show that the SILS
      approach is safe and does not increase operative time. In conclusion, SILS
      laparoscopic adjustable gastric banding is a safe and effective means of
      attaining weight loss in selected patients.

PMID- 23152116
TI  - Diatom frustules as light traps enhance DSSC efficiency.
AB  - Diatoms are one of the most successful photosynthetic organisms and given the
      important role that their shells (frustules) play in light trapping we explored
      their use in multilayered materials for application as photoanodes in dye
      sensitised solar cells (DSSCs). We find a substantial improvement in energy
      conversion efficiency of 30%, increasing from 3.5% to 4.6% with diatom
      incorporation.

PMID- 23152114
TI  - Adenosine A2A receptor modulates vascular response in soluble epoxide hydrolase
      null mice through CYP-epoxygenases and PPARgamma.
AB  - The interaction between adenosine and soluble epoxide hydrolase (sEH) in vascular
      response is not known. Therefore, we hypothesized that lack of sEH in mice
      enhances adenosine-induced relaxation through A(2A) adenosine receptors (AR) via
      CYP-epoxygenases and peroxisome proliferator-activated receptor gamma
      (PPARgamma). sEH(-/-) showed an increase in A(2A) AR, CYP2J, and PPARgamma by
      31%, 65%, and 36%, respectively, and a decrease in A(1)AR and PPARalpha (30% and
      27%, respectively) vs. sEH(+/+). 5'-N-ethylcarboxamidoadenosine (NECA, an
      adenosine receptor agonist), CGS 21680 (A(2A) AR-agonist), and GW 7647 (PPARalpha
      agonist)-induced responses were tested with nitro-l-arginine methyl ester (l
      NAME) (NO-inhibitor; 10(-4) M), ZM-241385, SCH-58261 (A(2A) AR-antagonists; 10(
      6) M), 14,15-epoxyeicosa-5(Z)-enoic acid (14,15-EEZE, an epoxyeicosatrienoic acid
      antagonist; 10(-5) M), 12-(3-adamantan-1-yl-ureido) dodecanoic acid (AUDA; 10
      MUM) or trans-4-[4-(3-adamantan-1-yl-ureido)-cyclohexyloxy]-benzoic acid (t-AUCB,
      sEH-inhibitors; 10(-5) M), and T0070907 (PPARgamma-antagonist; 10(-7) M). In sEH(
      /-) mice, ACh response was not different from sEH(+/+) (P > 0.05), and l-NAME
      blocked ACh-responses in both sEH(-/-) and sEH(+/+) mice (P < 0.05). NECA (10(-6)
      M)-induced relaxation was higher in sEH(-/-) (+12.94 +/- 3.2%) vs. sEH(+/+) mice
      (-5.35 +/- 5.2%); however, it was blocked by ZM-241385 (-22.42 +/- 1.9%) and SCH
      58261(-30.04 +/- 4.2%). CGS-21680 (10(-6) M)-induced relaxation was higher in
      sEH(-/-) (+37.4 +/- 5.4%) vs. sEH(+/+) (+2.14 +/- 2.8%). l-NAME (sEH(-/-), +30.28
      +/- 4.8%, P > 0.05) did not block CGS-21680-induced response, whereas 14,15-EEZE
      (-7.1 +/- 3.7%, P < 0.05) did. Also, AUDA and t-AUCB did not change CGS-21680
      induced response in sEH(-/-) (P > 0.05), but reversed in sEH(+/+) (from +2.14 +/-
      2.8% to +45.33 +/- 4.1%, and +63.37 +/- 7.2, respectively). PPARalpha-agonist did
      not relax as CGS 21680 (-2.48 +/- 1.1 vs. +37.4 +/- 5.4%) in sEH(-/-), and
      PPARgamma-antagonist blocked (from +37.4 +/- 5.4% to +9.40 +/- 3.1) CGS 21680
      induced relaxation in sEH(-/-). Our data suggest that adenosine-induced
      relaxation in sEH(-/-) may depend on the upregulation of A(2A) AR, CYP2J, and
      PPARgamma, and the downregulation of A(1) AR and PPARalpha.

PMID- 23152117
TI  - Implementation of the ACR dose index registry at a large academic institution:
      early experience.
AB  - A rising conciousness within both the medical community and in the public has
      been created by the current levels of radiation exposure from increased use of
      computed tomography. The concern has prompted the need for more data collection
      and analysis of hospital and imaging center exam doses. This has spurred the
      American College of Radiology (ACR) to develop the Dose Index Registry (DIR),
      which will allow participating insitutions to compare the radiation dose from
      their CT exams to aggregate national CT dose data based on exam type and body
      part. We outline the steps involved in the process of enrolling in the DIR, the
      technical requirements, the challenges we encountered, and our solutions to those
      challenges. A sample of the quaterly report released by the ACR is presented and
      discussed. Enrolling in the ACR dose registry is a team effort with participation
      from IT, a site physicist, and a site radiologist. Participation in this registry
      is a great starting point to initiate a QA process for monitoring CT dose if none
      has been established at an institution. The ACR has developed an excellent
      platform for gathering, analyzing, and reporting CT dose data. Even so, each
      insititutions will have its own unique issues in joining the project.

PMID- 23152118
TI  - Defragmenting catalysis.

PMID- 23152120
TI  - Authors' reply.

PMID- 23152121
TI  - Adequacy of pathology reports of specimens from patients with differentiated
      thyroid cancer.
AB  - This study aims to investigate the adequacy of pathology reports of specimens
      from patients with differentiated thyroid cancer (DTC) operated in our
      institution. Retrospective analysis of the pathology reports of all patients
      diagnosed with DTC in our area, from 1 January 2006 through 30 June 2011, was
      done. Sixty-eight patients were diagnosed with DTC. All reports were descriptive.
      In all the reports, but one, one or more core data items (according to the Royal
      College of Pathologists) were missing. Information about 1 and 2 items was
      lacking in 7.4 and 42.6 % of the reports, respectively. The rest were missing
      three or more data. Lymphovascular invasion, histology subtype, and completeness
      of excision were, in this order, the three most frequently omitted data.
      Sometimes, the information in question was not explicitly expressed but could be
      extrapolated from the data available. The pathology reports of DTC specimens
      frequently miss some of the information considered necessary to provide a
      comprehensive patient care.

PMID- 23152122
TI  - Skipping breakfast: morningness-eveningness preference is differentially related
      to state and trait food cravings.
AB  - Eveningness preference is associated with unhealthy eating behaviors. We measured
      state and trait food cravings in chronotypes in the morning and in the evening.
      Less Evening (E)- than Morning (M)-types reported to have had breakfast.
      Accordingly, hours that had elapsed since the last meal were higher in E- than M
      types in the morning, but did not differ between groups in the evening. E-types
      reported higher anticipation of positive reinforcement that may result from
      eating than M-types in the morning, but both had the same hunger levels. On a
      trait level, M-types reported more feelings of guilt for giving into cravings
      compared to E-types. Results suggest that E-types skip breakfast more often than
      M-types, but this eating pattern does not inevitably lead to more food cravings
      in the evening or more pronounced habitual cravings. Furthermore, E-types did not
      experience more hunger in the morning although they had not been eating for a
      longer time period. Results support findings about a different lifestyle in E
      types compared to M-types.

PMID- 23152123
TI  - The use of ovarian vessels for microvascular tissue transfer in lower extremity
      limb salvage.
AB  - Limb salvage procedures in previously operated, radiated, and vessel-depleted
      fields rely heavily on the use of microvascular tissue transfer. This report
      illustrates the feasibility of the use of ovarian vessels for the
      revascularization of a free flap. We have achieved success with the use of rectus
      abdominis muscle free flap for coverage of exposed vascular reconstruction in the
      75-year-old soft tissue sarcoma patient with twice chemoradiated femoral and
      hypogastric defect, preventing external hemipelvectomy.

PMID- 23152125
TI  - Impact of transplant nephrectomy on retransplantation: a single-center
      retrospective study.
AB  - PURPOSE: Kidney retransplantation is the best treatment option for transplanted
      patients returning to dialysis. The aim of this study was to explore the effect
      of removal of a failed graft on the outcome of a subsequent transplant. METHODS:
      We identified 140 patients who underwent retransplantation at our institution.
      Retrospective comparison was performed between patients undergoing kidney
      retransplantation with (group A, n = 28) and without (group B, n = 112)
      preliminary nephrectomy. Graft and patient survival were calculated by the Kaplan
      Meier method. RESULTS: After a mean follow-up of 64.5 months, patients survival
      was comparable between the two groups (group A = 68.6 vs. group B = 63.5 months;
      p = 0.6). Mean graft survival was 65.5 versus 56.0 months in group A and B,
      respectively (p = 0.14). Surgical complications after retransplantation were
      significantly higher in group A compared to group B (57.1 vs. 19.6 %; p =
      0.0002). There was no significant difference between the two groups in the panel
      reactive antibody level at the time of retransplantation (group A = 20 % vs.
      group B = 32 %; p = 0.22). The acute rejection rate was 35.7 % in group A and 25
      % in group B (p = 0.36). The risk of delayed graft function was not significantly
      increased in group A (p = 0.63). Finally, 2 years after retransplantation,
      patients who had not undergone nephrectomy had lower serum creatinine
      concentrations (1.3 vs. 1.7 mg/dl; p = 0.01) and higher estimated GFR (77.9 vs.
      59.3 ml/min/1.73 m(2); p = 0.02). CONCLUSION: Our experience shows that there is
      no advantage in performing allograft nephrectomy before retransplantation, and
      that this procedure does not seem to significantly influence the survival of a
      subsequent graft.

PMID- 23152124
TI  - Involvement of lysosomal exocytosis in the excretion of mesoporous silica
      nanoparticles and enhancement of the drug delivery effect by exocytosis
      inhibition.
AB  - The exocytosis of phosphonate modified mesoporous silica nanoparticles (P-MSNs)
      is demonstrated and lysosomal exocytosis is identified as the mechanism
      responsible for this event. Regulation of P-MSN exocytosis can be achieved by
      inhibiting or accelerating lysosomal exocytosis. Slowing down P-MSN exocytosis
      enhances the drug delivery effect of CPT-loaded P-MSNs by improving cell killing.

PMID- 23152126
TI  - Prognostic significance of disease-free interval in head and neck cutaneous
      squamous cell carcinoma with nodal metastases.
AB  - BACKGROUND: The purpose of this study was to determine whether the disease-free
      interval (DFI) between treatment of primary head and neck cutaneous squamous cell
      carcinoma (SCC) and the development of regional metastases is an independent
      prognostic factor. METHODS: A retrospective analysis of 229 patients with
      metastatic nodal head and neck cutaneous SCC, treated with curative intent by
      surgery +/- adjuvant radiotherapy was conducted. RESULTS: After adjusting for the
      effect of nodal staging, extracapsular spread, involved margins, adjuvant
      radiotherapy, and immunosuppression, a short DFI (<=9 months vs >9 months) was a
      significant predictor of disease-related mortality (hazard ratio [HR], 3.0; 95%
      confidence interval [CI], 1.4-6.5; p = .004) and locoregional relapse (HR, 2.0;
      95% CI, 1.1-4.0; p = .044). CONCLUSION: The DFI is a potentially powerful
      independent prognostic factor in patients with regional metastases secondary to
      head and neck cutaneous SCC. It provides information before definitive treatment
      that may ultimately assist clinicians in applying a risk-adapted management
      paradigm.

PMID- 23152127
TI  - Ornithine decarboxylase and glutamate decarboxylase 65 as prognostic markers of
      gallbladder malignancy: a clinicopathological study in benign and malignant
      lesions of the gallbladder.
AB  - Ornithine decarboxylase (ODC) plays a critical role in cell proliferation and is
      overexpressed in a variety of cancers. Furthermore, gamma-aminobutyric acid
      (GABA) content and glutamate decarboxylase (GAD) activity are increased in
      neoplastic tissues in colon and breast cancer. However, few studies have examined
      these molecules in gallbladder cancer specimens. We observed the expression
      levels of ODC and GAD65 in benign and malignant lesions of the gallbladder and
      investigated their clinicopathological significance for the first time. The
      expression levels of ODC and GAD65 in specimens from gallbladder adenocarcinoma
      (n=108), peritumoral tissues (n=46), adenomatous polyps (n=15) and chronic
      cholecystitis (n=35) were detected using immunohistochemical methods. Kaplan
      Meier survival and Cox regression analyses were carried out to explore the
      clinical and pathological correlations. The levels of positive staining of ODC
      and GAD65 were significantly higher in gallbladder adenocarcinoma than in
      peritumoral tissues, adenomatous polyps and chronic cholecystitis. The Kaplan
      Meier survival analysis and Cox regression analysis showed that the expression of
      ODC and GAD65 correlated significantly with the one-year survival rate and the
      mean survival time of the patients postoperatively. We conclude that the
      overexpression of ODC and GAD65 are significant in the carcinogenesis and
      progression of gallbladder adenocarcinoma. They may be important biological
      markers for the evaluation of biological behaviors and the prognosis of
      gallbladder adenocarcinoma.

PMID- 23152128
TI  - Endoplasmic reticulum stress induces hepatic steatosis via increased expression
      of the hepatic very low-density lipoprotein receptor.
AB  - Recent evidence suggests that obese animals exhibit increased endoplasmic
      reticulum (ER) stress in the liver and adipose tissue. Although ER stress is
      closely associated with lipid homeostasis, it is largely unknown how ER stress
      contributes to hepatic steatosis. In this study, we demonstrate that the
      induction of ER stress stimulates hepatic steatosis through increased expression
      of the hepatic very low-density lipoprotein receptor (VLDLR). Among the unfolded
      protein response sensors, the protein kinase RNA-like ER kinase-activating
      transcription factor 4 signaling pathway was required for hepatic VLDLR up
      regulation. In primary hepatocytes, ER stress-dependent VLDLR expression induced
      intracellular triglyceride accumulation in the presence of very low-density
      lipoprotein. Moreover, ER stress-dependent hepatic steatosis was diminished in
      the livers of VLDLR-deficient and apolipoprotein E-deficient mice compared with
      wild-type mice. In addition, the VLDLR-deficient mice exhibited decreased hepatic
      steatosis upon high-fat diet feeding. CONCLUSION: These data suggest that ER
      stress-dependent expression of hepatic VLDLR leads to hepatic steatosis by
      increasing lipoprotein delivery to the liver, which might be a novel mechanism
      explaining ER stress-induced hepatic steatosis.

PMID- 23152129
TI  - High-density lipoprotein cholesterol subfractions and lecithin: cholesterol
      acyltransferase activity in collegiate soccer players.
AB  - Many of the published data on the lipid profile of athletes is based on studies
      of endurance athletes. The data on soccer players are rare. The purpose of this
      study was to examine serum high-density lipoprotein cholesterol subfractions and
      lecithin:cholesterol acyltransferase activity in collegiate soccer players. 31
      well-trained male collegiate soccer players were divided into 2 groups: 16
      defenders and 15 offenders. They were compared with 16 sedentary controls.
      Dietary information was obtained with a food frequency questionnaire. The
      subjects were all non-smokers and were not taking any drug known to affect the
      lipid and lipoprotein metabolism. The offenders had significantly higher high
      density lipoprotein cholesterol, high-density lipoprotein2 cholesterol, and
      apolipoprotein A-I than the defenders and controls, whereas the defenders had the
      significantly higher high-density lipoprotein2 cholesterol than the controls.
      Both groups of athletes had significantly higher lecithin:cholesterol
      acyltransferase activity than the controls. The results indicate that favorable
      lipid and lipoprotein profile could be obtained by vigorous soccer training.

PMID- 23152130
TI  - CK19 expression should be tested prior to OSNA analysis of sentinel lymph nodes
      in breast cancer.

PMID- 23152131
TI  - Nonlinearity in the relationship between bone lead concentrations and CBLI for
      lead smelter employees.
AB  - 494 smelter employees from New Brunswick participated in a bone lead survey
      conducted by McMaster University in 2008, using the four element "clover-leaf"
      geometry germanium detector system. The employees were measured at two different
      bone sites, tibia and calcaneus, each measurement lasting 30 minutes. Scattered
      photons, including Pb X-rays, were collected by the germanium detectors located
      behind the 109Cd source. A strong positive correlation was observed between tibia
      and calcaneus lead concentrations. Having been provided with blood lead levels, a
      cumulative blood lead index (CBLI) was generated. The employees were classified
      into four groups based on their date of hire, and their CBLI levels were compared
      to their tibia and calcaneus lead concentrations in the different groups. The
      slopes of bone Pb versus CBLI varied amongst groups, with those hired earliest
      showing the steepest slopes. This could be taken to imply a non-linearity in the
      uptake of Pb by bone from blood. In this paper, the association of the bone lead
      concentrations versus CBLI has been expressed by a polynomial function for the
      whole group of employees.

PMID- 23152132
TI  - Ginsenoside Rh2 mediates changes in the microRNA expression profile of human non
      small cell lung cancer A549 cells.
AB  - Non-small cell lung cancer (NSCLC) is the most common type of lung cancer
      insensitive to chemotherapy. Efforts are, therefore, directed toward
      understanding the molecular mechanisms of chemotherapy insensitivity and the
      development of new anticancer drugs. Ginsenoside Rh2, one of the components in
      ginseng saponin, has been shown to have anti-proliferative effect on human NSCLC
      cells and is being studied as a therapeutic drug for NSCLC. microRNAs (miRNAs)
      are small, non-coding RNA molecules that play a key role in cancer progression
      and prevention. However, the miRNA portrait of ginsenoside Rh2-treated NSCLC
      cells has not yet been studied. In this study, we identified a unique set of
      changes in the miRNA expression profile in response to Rh2 treatment in the human
      NSCLC cell line A549. Using miRNA microarray analysis, we identified 44 and 24
      miRNAs displaying changes in expression greater than 2-fold in Rh2-treated A549
      cells. In addition, using an miRNA target prediction program, we discovered that
      these miRNAs are predicted to have several target genes related to angiogenesis,
      apoptosis, chromatic modification, cell proliferation and differentiation. Thus,
      these results may assist in the better understanding of the anticancer mechanism
      of Rh2 in NSCLC.

PMID- 23152133
TI  - Randomized control study of the outback LTD reentry catheter versus manual
      reentry for the treatment of chronic total occlusions in the superficial femoral
      artery.
AB  - PURPOSE: To assess the efficacy and safety of the Outback device in patients with
      a chronic total occlusion (CTO) of the superficial femoral artery and evaluate
      its impact on fluoroscopy and procedural times. MATERIALS AND METHODS: From
      October 2006 to March 2007, 52 patients affected by TASC II-D superficial femoral
      artery CTO were treated with subintimal recanalization. Clinical indications for
      endovascular recanalization were: claudication, tissue loss, and at rest leg pain
      with critical limb ischemia. In 26 patients the manual reentry technique was used
      and in 26 the OUTBACK((r)) LTD Re-Entry Catheter was used. Total procedure time,
      fluoroscopy time and precision in targeting the expected reentry site have been
      compared. RESULTS: Technical success was achieved in all cases (100%). In group
      2, the planned in-target re-entry was achieved in 11/26 cases (42.3%). The
      procedure was performed with a traditional antegrade approach in 23/26 (88.4%)
      cases and in three cases (11.6%) a combined antegrade/retrograde approach was
      necessary. In group 1, the in-target re-entry was achieved in 26/26 cases (100%).
      In group 2, the mean procedural time was 55.4 +/- 14.2 min with a mean
      fluoroscopy time 39.6 +/- 13.9 min compared to 36.0 +/- 9.4 min and 29.8 +/- 8.9
      min, respectively, of group 1 (P < 0.0001). CONCLUSIONS: In our experience, the
      use of this device is very useful for the revascularization of chronic femoral
      occlusions, even calcific, in which an accurate re-entry cannot be achieved with
      the conventional subintimal technique. In these cases, the Outback device grants
      high technical success rates and a significant reduction of procedural and
      fluoroscopy times.

PMID- 23152134
TI  - What is overt and what is covert in congenital prosopagnosia?
AB  - The term covert recognition refers to recognition without awareness. In the
      context of face recognition, it refers to the fact that some individuals show
      behavioural, electrophysiological or autonomic indices of recognition in the
      absence of overt, conscious recognition. Originally described in cases of people
      that have lost their ability to overtly recognize faces (acquired prosopagnosia,
      AP), covert face recognition has more recently also been described in cases of
      congenital prosopagnosia (CP), who never develop typical overt face recognition
      skills. The presence of covert processing in a developmental disorder such as CP
      is a particularly intriguing phenomenon, and its investigation is relevant for a
      variety of reasons. From a theoretical point of view, it is useful to help shed
      light on the cognitive and neural underpinnings of face recognition deficits.
      From a clinical point of view, it has the potential to aid the design of
      rehabilitation protocols aimed at improving face recognition skills in this
      population. In the current review we selectively summarize the recent literature
      on covert face recognition in CP, highlight its main findings, and provide a
      theoretical interpretation for them.

PMID- 23152135
TI  - Decompressive hemicraniectomy reduces mortality in an animal model of
      intracerebral hemorrhage.
AB  - Decompressive hemicraniectomy (DHC) significantly reduces mortality in patients
      with large hemispheric ischemic strokes but has not been studied in intracranial
      hemorrhage (ICH). Male Sabra mice were subjected to large experimental ICH. The
      animals then underwent DHC or sham surgery. Early (1 day post-op) and late (5
      days post-op) mortality rates and neurological disability were monitored. The
      animals were perfusion-fixed at 5 days post-ICH induction, and their brains were
      studied for hematoma volume and presence of active caspase 3 as a measure of
      apoptotic death in the area surrounding the hematoma. Our results show that DHC
      significantly reduced early (7 vs. 75 %, p < 0.001) and late (46 vs. 83 %, p =
      0.017) mortality after large ICH. No significant differences in neurological
      disability were observed between surviving animals in both groups. Hematoma
      volumes did not differ between the groups on histological evaluation. The number
      of active caspase 3-positive neurons at the hematoma boundary was significantly
      higher in animals that underwent DHC. In conclusion, DHC reduces early and late
      mortality after devastating ICH without changing the hematoma volumes and without
      notable effects on motor and sensory functions in survivors. Further evaluation
      of this method to reduce mortality in ICH patients is warranted.

PMID- 23152137
TI  - Adsorption chromatography separation of the flavonols kaempferol, quercetin and
      myricetin using cross-linked collagen fibre as the stationary phase.
AB  - BACKGROUND: Kaempferol, quercetin and myricetin are typical flavonols that are
      most concentrated in many medicinal herbs. However, the separation of these
      flavonols is very challenging due to their similar molecular structures. In the
      present investigation, the chromatographic separation of the flavonols
      kaempferol, quercetin and myricetin was performed using glutaraldehyde cross
      linked collagen fibre (GCF) as the stationary phase. RESULTS: Kaempferol,
      quercetin and myricetin could be completely separated from each other by the GCF
      column by using gradient elution with different solutions of aqueous ethanol
      (100% to 70%) and 50% acetone. When the chromatographic separation was carried
      out at a flow rate of 0.75 bed volume h(-1) with a sample loading of 30 mg 7 g(
      1) GCF, the purity of kaempferol, quercetin and myricetin was 98.17%, 93.81% and
      81.76%, respectively. The separation resolution was influenced by column length,
      flow rate and sample loading amount. The separation efficiency of GCF was not
      obviously reduced after applications had been repeated five times. In the fifth
      repeated application, the purity of the recovered kaempferol, quercetin and
      myricetin was still higher than 97%, 94% and 78%, respectively. CONCLUSION: GCF
      is a promising adsorbent for use as a stationary phase in the chromatographic
      separation of flavonols from their mixtures.

PMID- 23152136
TI  - Proteomic snapshot of breast cancer cell cycle: G1/S transition point.
AB  - The biological processes that unfold during the G1-phase of the cell cycle are
      dependent on extracellular mitogenic factors that signal the cell to enter a
      state of quiescence, or commit to a cell-cycle round by passing the restriction
      point (R-point) and enter the S-phase. Unlike normal cells, cancer cells evolved
      the ability to evade the R-point and continue through the cell cycle even in the
      presence of extensive DNA damage or absence of mitogenic signals. The purpose of
      this study was to perform a quantitative proteomic evaluation of the biological
      processes that are responsible for driving MCF-7 breast cancer cells into
      division even when molecular checkpoints such as the G1/S R-point are in place.
      Nuclear and cytoplasmic fractions of the G1 and S cell-cycle phases were analyzed
      by LC-MS/MS to result in the confident identification of more than 2700 proteins.
      Statistical evaluation of the normalized data resulted in the selection of
      proteins that displayed twofold or more change in spectral counts in each cell
      state. Pathway mapping, functional annotation clustering, and protein interaction
      network analysis revealed that the top-scoring clusters that could play a role in
      overriding the G1/S transition point included DNA damage response, chromatin
      remodeling, transcription/translation regulation, and signaling proteins.

PMID- 23152138
TI  - Work-related risk factors for lateral epicondylitis and other cause of elbow pain
      in the working population.
AB  - BACKGROUND: This study was designed to assess the relationship between work
      related combined physical and psychosocial factors and elbow disorders (lateral
      epicondylitis and non-specific disorders without lateral epicondylitis) in the
      working population. METHODS: A total of 3,710 workers (58% men) in a French
      region in 2002-2005 participated in physical examinations by occupational health
      physicians and assessed their personal factors and work exposure by self
      administered questionnaire. Statistical associations between elbow disorders and
      risks factors were analyzed using multinomial logistic regression. RESULTS: A
      total of 389 (10.5%) workers had elbow pain without lateral epicondylitis and 90
      (2.4%) workers had lateral epicondylitis. Age, body mass index (>25), and low
      social support (only for men) were significant risks factors. Hard perceived
      physical exertion combined with elbow flexion/extension (>2 hr/day) and wrist
      bending (>2 hr/day) was a strong significant risk factor for elbow pain and
      epicondylitis: among men, adjusted Odds Ratio (ORa) = 2.6 (1.9-3.7) and ORa = 5.6
      (2.8-11.3), respectively; among women, ORa = 1.4 (0.9-2.2) and ORa = 2.9 (1.3
      6.5). CONCLUSIONS: This study emphasizes the strength of the associations between
      combined physical exertion and elbow movements and lateral epicondylitis. Certain
      observed differences in associations with lateral epicondylitis and elbow pain
      only indicate the need for additional longitudinal studies on different stages of
      elbow disorders and known risk factors.

PMID- 23152139
TI  - The structure of a shellfish specific GST class glutathione S-transferase from
      antarctic bivalve Laternula elliptica reveals novel active site architecture.
AB  - Glutathione-S-transferases have been identified in all the living species
      examined so far, yet little is known about their function in marine organisms. In
      a previous report, the recently identified GST from Antarctic bivalve Laternula
      elliptica (LeGST) was classified into the rho class GST, but there are several
      unique features of LeGST that may justify reclassification, which could represent
      specific shellfish GSTs. Here, we determined the crystal structure of LeGST,
      which is a shellfish specific class of GST. The structural analysis showed that
      the relatively open and wide hydrophobic H-site of the LeGST allows this GST to
      accommodate various substrates. These results suggest that the H-site of LeGST
      may be the result of adaptation to their environments as sedentary organisms.

PMID- 23152140
TI  - Autonomic dysfunction in SCN9A-associated primary erythromelalgia.
AB  - Primary erythromelalgia (EM) is an autosomal dominant disorder caused by
      mutations of SCN9A. It is clinically characterized by reddish discoloration and
      episodic burning sensation of distal extremities triggered by warmth. We report a
      49-year-old male with primary EM caused by SCN9A mutation (p.F216S), in whom an
      autonomic reflex screening test revealed a mild sudomotor dysfunction.

PMID- 23152141
TI  - Use of a combined latissimus dorsi scapular free flap revascularized with vein
      grafting to the internal mammary artery in a vessel-depleted and previously
      irradiated neck.
AB  - BACKGROUND: For patients who have extensive prior treatment, use of the internal
      mammary artery/vein (IMA/IMV) or cephalic vein has been shown to be a reliable
      option. Additionally, for those patients who require vascularized bone and
      extensive soft tissue reconstruction, the combined latissimus dorsi scapular free
      flap (mega-flap) is an excellent option. METHODS: We reviewed 3 cases in which
      extensive prior surgery and radiation precluded the use of traditional recipient
      vessels in the neck. RESULTS: Three patients with major jaw deformities were
      reconstructed using a mega-flap. In all cases, saphenous vein grafting succeeded
      in achieving arterial inflow from the IMA to the subscapular artery. Venous
      egress was achieved using a vein graft to the IMV in 1 patient and a transposed
      cephalic vein in the remaining 2 patients. CONCLUSIONS: This approach of
      restoring large oral cavity defects for patients with extensive prior therapy and
      comorbid conditions has proven to be reliable and reproducible.

PMID- 23152142
TI  - Enhanced binding of tissue factor-microparticles to collagen-IV and fibronectin
      leads to increased tissue factor activity  in vitro.
AB  - The role of tissue factor (TF)-containing microparticles in clot propagation has
      been established, but the ability of circulating microparticles to initiate
      coagulation has been disputed. However, TF-bearing microparticles, particularly
      endothelial-microparticles generated during disease, may interact with
      extracellular matrices which in turn can localise circulating TF to sites of
      injury. In order to examine this hypothesis  in vitro , microparticles were
      isolated from human coronary artery endothelial cells transfected to overexpress
      TF, tumour-necrosis factor  (TNF) alpha-treated cells or non-transfected cells
      lacking TF. The ability of microparticles to bind collagen-IV, fibronectin and
      fibrin was examined under static conditions and arterial shear rates (650 s-1),
      and also in the presence of inhibitory antibodies against beta1-, beta3-, alpha3-
      and alphav-integrins or an anti-TF antibody. TF-microparticles showed increases
      of up to 43% and 24% in adherence to collagen-IV and fibronectin, respectively,
      compared to control microparticles under shear flow. Furthermore, TF-containing
      microparticles, but not the transfected parent cells had increased levels of
      beta1-integrin compared to TF-deficient microparticles. Pre-incubation of
      microparticles with a beta1-integrin-blocking antibody counteracted the
      additional adhesion of TF-microparticles compared to control microparticles.
      Finally, adherence of TF microparticles to collagen-IV or fibronectin resulted in
      increased TF activity by concentrating TF onto the surface. In conclusion, the
      presence of TF within microparticles enhances the interactions of endothelial
      cell-derived microparticles with extracellular matrices in an integrin-dependent
      manner. Accumulation and localisation of these microparticles in turn results in
      the enhancement of TF activity. This may be an innate mechanism by which TF
      bearing microparticles induce coagulation upon vascular injury.

PMID- 23152143
TI  - Temporal trends of mercury in Greenland ringed seal populations in a warming
      climate.
AB  - Temporal trends of mercury in livers of ringed seals collected from the early
      1980s to 2010 from central West, Northwest and central East Greenland were
      studied. In this period the climate of Greenland warmed and the influences of
      climate indices such as ice coverage, water temperature and the Atlantic
      Oscillation Index on mercury concentration were evaluated using multiple
      regressions and Akaike's Information Criteria (AIC) to determine the most
      parsimonious models. Biological co-variables such as age, sex and trophic
      position (as determined by stable isotope analysis) of seals were also evaluated.
      Increasing levels of mercury in seals were found in Ittoqqortoormiit, central
      East Greenland, and Avanersuaq, Northwest Greenland, with an annual increase of
      +10.3 and +2%, respectively. Age was an important co-variable for all three
      regions and trophic position for two regions. The Atlantic Oscillation Index was
      also an important explanatory variable for all three regions and was positively
      associated with mercury concentrations in seals indicating the importance of
      global climatic processes on ringed seal populations in Greenland.

PMID- 23152145
TI  - Development and validation of an assessment of adult educators' reading
      instructional knowledge.
AB  - The purpose of this paper is to describe briefly the development and utility of
      the Assessment of Reading Instructional Knowledge-Adults (ARIK-A), the only
      nationally normed (n = 468) measure of adult reading instructional knowledge,
      created to facilitate professional development of adult educators. Developmental
      data reveal reliabilities ranging from 0.73 to 0.85 for five ARIK-A scales
      (alphabetics, fluency, vocabulary, comprehension, and assessment) and 0.91 for
      the composite score; factor analytic data and expert review provide support for
      construct validity as well. Information on how to use the ARIK-A to determine
      mastery and relative standing is presented. With two alternate forms, the ARIK-A
      is a promising and needed tool for adult education practitioners within
      continuing education and professional development contexts. 

PMID- 23152147
TI  - Direct MC conversion of absorbed dose to graphite to absorbed dose to water for
      60Co radiation.
AB  - The ARPANSA calibration service for (60)Co gamma rays is based on a primary
      standard graphite calorimeter that measures absorbed dose to graphite.
      Measurements with the calorimeter are converted to the absorbed dose to water
      using the calculation of the ratio of the absorbed dose in the calorimeter to the
      absorbed dose in a water phantom. ARPANSA has recently changed the basis of this
      calculation from a photon fluence scaling method to a direct Monte Carlo (MC)
      calculation. The MC conversion uses an EGSnrc model of the cobalt source that has
      been validated against water tank and graphite phantom measurements, a step that
      is required to quantify uncertainties in the underlying interaction coefficients
      in the MC code. A comparison with the Bureau International des Poids et Mesures
      (BIPM) as part of the key comparison BIPM.RI(I)-K4 showed an agreement of 0.9973
      (53).

PMID- 23152146
TI  - Eye lens dosimetry in interventional cardiology: results of staff dose
      measurements and link to patient dose levels.
AB  - Workers involved in interventional cardiology procedures receive high eye lens
      dose if protection is not used. Currently, there is no suitable method for
      routine use for the measurement of eye dose. Since most angiography machines are
      equipped with suitable patient dosemeters, deriving factors linking staff eye
      doses to the patient doses can be helpful. In this study the patient kerma-area
      product, cumulative dose at an interventional reference point and eye dose in
      terms of Hp(3) of the cardiologists, nurses and radiographers for interventional
      cardiology procedures have been measured. Correlations between the patient dose
      and the staff eye dose were obtained. The mean eye dose was 121 uSv for the first
      operator, 33 uSv for the second operator/nurse and 12 uSv for radiographer.
      Normalised eye lens doses per unit kerma-area product were 0.94 uSv Gy-1 cm-2 for
      the first operator, 0.33 uSv Gy-1 cm-2 for the second operator/nurse and 0.16 uSv
      Gy-1 cm-2 for radiographers. Statistical analysis indicated that there is a weak
      but significant (p < 0.01) correlation between the eye dose and the kerma-area
      product for all three staff categories. These values are based on a local
      practice and may provide useful reference for other studies for validation and
      for wider utilisation in assessing the eye dose using patient dose values.

PMID- 23152144
TI  - Postnatal isoform switch and protein localization of LEF1 and TCF7L2
      transcription factors in cortical, thalamic, and mesencephalic regions of the
      adult mouse brain.
AB  - beta-Catenin signaling, leading to the activation of lymphoid enhancer-binding
      factor 1/T cell factor (LEF1/TCF) transcription factors, plays a well-established
      role in transcription regulation during development and tissue homeostasis. In
      the adult organism, the activity of this pathway has been found in stem cell
      niches and postmitotic thalamic neurons. Recently, studies show that mutations in
      components of beta-catenin signaling networks have been associated with several
      psychiatric disorders, indicating the involvement of beta-catenin and LEF1/TCF
      proteins in the proper functioning of the brain. Here, we report a comprehensive
      analysis of LEF1/TCF protein localization and the expression profile of their
      isoforms in cortical, thalamic, and midbrain regions in mice. We detected LEF1
      and TCF7L2 proteins in neurons of the thalamus and dorsal midbrain, i.e.,
      subcortical regions specialized in the integration of diverse sources of sensory
      information. These neurons also exhibited nuclear localization of beta-catenin,
      suggesting the involvement of beta-catenin/LEF1/TCF7L2 in the regulation of gene
      expression in these regions. Analysis of alternative splicing and promoter usage
      identified brain-specific TCF7L2 isoforms and revealed a developmentally
      coordinated transition in the composition of LEF1 and TCF7L2 isoforms. In the
      case of TCF7L2, the typical brain isoforms lack the so-called C clamp; in
      addition, the dominant-negative isoforms are predominant in the embryonic
      thalamus but disappear postnatally. The present study provides a necessary
      framework to understand the role of LEF1/TCF factors in thalamic and midbrain
      development until adulthood and predicts that the regulatory role of these
      proteins in the adult brain is significantly different from their role in the
      embryonic brain or other non-neural tissues. 

PMID- 23152148
TI  - Lipase activity, mesocarp oil content, and iodine value in oil palm fruits of
      Elaeis guineensis, Elaeis oleifera, and the interspecific hybrid O*G (E. oleifera
      * E. guineensis).
AB  - BACKGROUND: One factor affecting crude palm oil quality is the formation of free
      fatty acids (FFA), often attributed to the hydrolytic action of mesocarp lipase.
      The aim of this work was to evaluate the enzyme behavior and to look toward new
      genotypes with low FFA production, high yield, and better oil quality. RESULTS:
      Lipase activity was strongly activated at low temperatures (5  degrees C). At
      this temperature PLL, SOO, POL, and POO (P, palmitic; L, linoleic; S, stearic; O,
      oleic) were the most hydrolyzed triacylglycerols in Elaeis guineensis fruits.
      Ethylene production decreased from 36 nL g(-1) h(-1) at room temperature to 2 nL
      g(-1) h(-1) at 5  degrees C. Lipase activity of E. guineensis, the E. oleifera *
      E. guineensis (O*G) hybrid, and E. oleifera were 52.7%, 32.9%, and <0.6% FFA,
      respectively. The E. guineensis showed oil in the mesocarp of 54.7%, followed by
      the O*G hybrid (47.0%), and E. oleifera (13.6%), and the iodine values were 52.0,
      66.3, and 77.4 g I(2) 100 g(-1), respectively. CONCLUSIONS: This work allowed the
      identification of interspecific O*G hybrids as promising crosses with less lipase
      activity and higher iodine value than E. guineensis. Although O*G crosses produce
      less oil in the mesocarp than commercial E. guineensis; this feature could be
      improved by further breeding to introduce new genes from E. oleifera into the
      hybrids.

PMID- 23152149
TI  - A rapid diagnostic technique of Bactrocera cucurbitae and Bactrocera zonata
      (Diptera: Tephritidae) for quarantine application.

PMID- 23152150
TI  - Comments on the contribution life, autonomy and cognition.

PMID- 23152151
TI  - [Patient education and treatment documentation -- draft law to improve the rights
      of patients].

PMID- 23152152
TI  - [Diagnostics in laser refractive surgery].

PMID- 23152153
TI  - Quantitative and qualitative 2D electrophoretic analysis of differentially
      expressed mitochondrial proteins from five mouse organs.
AB  - Mitochondria fulfill many tissue-specific functions in cell metabolism. We set
      out to identify differences in the protein composition of mitochondria from five
      tissues frequently affected by mitochondrial disorders. The proteome of highly
      purified mitochondria from five mouse organs was separated by high-resolution
      2DE. Tissue-specific spots were identified through nano-LC/ESI-MS/MS and
      quantified by densitometry in ten biological replicates. We identified 87
      consistently deviating spots representing 48 proteins. The percentage of variant
      spots ranged between 4.2% and 6.0%; 21 proteins having tissue-specific isospots.
      Consistent tissue-specific processing/regulation was seen for carbamoyl-phosphate
      synthase, aldehyde-dehydrogenase 2, ATP-synthase alpha-chain, and isocitrate
      dehydrogenase alpha-subunit. Thirty tissue-specific proteins were associated with
      mitochondrial disorders in humans. We further identified alcohol-dehydrogenase,
      catalase, quinone-oxidoreductase, cyclophilin-A, and Upf0317, a potential biotin
      carboxyl-carrier protein, which had not been annotated as "mitochondrial" in Gene
      Ontology or MitoCarta databases. Their targeting to the mitochondria was verified
      by transfection of full-length GFP-tagged plasmids. Given the high evolutionary
      conservation of mitochondrial metabolic pathways, these data further annotate the
      mitochondrial proteome and advance our understanding of the pathophysiology and
      tissue-specificity of symptoms seen in patients with mitochondrial disorders. The
      generation of 2D electrophoretic maps of the mitochondrial proteome using tissue
      specimens in the milligram range facilitates this technique for clinical
      applications and biomarker research.

PMID- 23152154
TI  - Baclofen did not modify sexually dimorphic c-Fos expression during morphine
      withdrawal syndrome.
AB  - In previous studies, we have reported sex-related differences during morphine
      withdrawal. We have also shown that the GABA(B) agonist baclofen (BAC) was able
      to prevent the morphine withdrawal syndrome in male as well as in female mice.
      Considering that early gene expression is induced by drugs of abuse, we evaluated
      the expression of c-Fos in several brain areas, in mice of either sex during
      naloxone (NAL)-precipitated withdrawal, and after pretreatment with BAC. Swiss
      Webster prepubertal mice were rendered dependent by i.p. injection of morphine (2
      mg/kg), twice daily for 9 days. On the 10th day, dependent mice were divided into
      two groups: the withdrawal group received NAL (6 mg/kg, i.p.) after the last dose
      of morphine, while the prevention group received BAC (2 mg/kg, i.p.) before NAL.
      Thirty minutes after NAL, animals were sacrificed by transcardial perfusion.
      Brains were removed and slices were obtained to perform immunohistochemical
      studies. Our results show a significant decrease in c-Fos expression in
      hippocampal dentate gyrus, CA3, and CA1 areas of morphine withdrawn males, vs.
      their control group. Conversely, in females, the number of c-Fos positive nuclei
      was not modified in any of the areas studied. BAC pretreatment had no effect on
      the decreased c-Fos expression in morphine withdrawn males. The sexual dimorphism
      observed here confirms the greater sensitivity of males over females in their
      response to morphine. The preventive action of BAC on the expression of morphine
      withdrawal would not be related to an effect on c-Fos expression.

PMID- 23152155
TI  - Protein kinase Calpha is involved in impaired perinatal hypothyroid rat brain
      development.
AB  - Protein kinase Calpha (PKCalpha) has been implicated in the regulation of a
      variety of cellular functions, such as proliferation, differentiation, and
      apoptosis, in response to a diverse range of stimuli. Activated PKCalpha mediates
      oxidative stress, apoptosis, and inflammatory reaction. Thyroid hormone (TH) is
      essential for the proper development of the mammalian central nervous system. TH
      deficiency during critical periods of brain development results in permanent
      cognitive and neurological impairments. In the present study, we attempted to
      explore whether PKCalpha is involved in impaired brain function in developing
      hypothyroid rat brain. Severe perinatal hypothyroidism was obtained by
      administration of 30 mg/day propylthiouracil to dams. Brain PKC activity in
      hypothyroid pups was increased significantly in cytosol and membrane fractions.
      The change of membrane PKC activity was more marked than that of cytosol, and
      hypothyroidism led to a higher ratio of membrane PKC activity to that in cytosol,
      which means abnormal activation of PKC in developing hypothyroid rat brain.
      Thyroxine replacement partially corrected these changes. After being treated with
      bisindolmaleimide XI, a mainly selective inhibitor for PKCalpha, the hypothyroid
      pups showed improved place navigation test results, and further Western blot
      analysis showed that PKCalpha expression in cytosol fractions was increased in
      hypothyroid rat brain with or without bisindolmaleimide XI treatment, but, after
      treatment with bisindolmaleimide XI, PKCalpha content in membrane fractions
      decreased almost to normal. Therefore, we conclude that PKCalpha appears to be
      involved in the impaired brain development observed in perinatal hypothyroid rat
      brain.

PMID- 23152156
TI  - Possible implications of acid-sensing ion channels in ischemia-induced retinal
      injury in rats.
AB  - BACKGROUND: Retinal ischemia in eyes with diabetic retinopathy and retinal vein
      occlusion leads to local tissue acidosis. Acid-sensing ion channels (ASICs) are
      expressed in photoreceptors and other neurons in the retina, and may play a role
      in acid-induced cell injury. The purpose of this study was to investigate the
      neuroprotective effects of amiloride, an ASIC blocker, on induced retinal
      ischemia in rats. METHODS: Transient retinal ischemia was induced in male Long
      Evans rats by the temporary ligation of the optic nerve. Just before the
      induction of ischemia, the experimental eyes underwent intravitreal injection of
      amiloride. On day 7, the retinal damage in eyes that underwent amiloride
      treatment (and in those that did not undergo the treatment) was evaluated by
      histology and electroretinogram (ERG). RESULTS: Transient retinal ischemia caused
      retinal degeneration with thinning of the inner layer of the retina. The blockage
      of ASICs with amiloride significantly prevented retinal degeneration. ERG
      demonstrated that the reduction in a- and b-wave amplitudes induced by the
      transient retinal ischemia was significantly prevented by the application of
      amiloride. CONCLUSIONS: The present study suggests that ASICs might, at least in
      part, play a pathophysiological role in ischemia-induced neurodegeneration.
      Blockage of ASICs may have a potential neuroprotective effect in ocular ischemic
      diseases.

PMID- 23152157
TI  - Comparative functional cell biological analysis of mesenchymal stem cells of the
      head and neck region: potential impact on wound healing, trauma, and infection.
AB  - BACKGROUND: Mesenchymal stem cells (MSCs) are multipotent mesenchymal progenitor
      cells, originally identified in bone-marrow. Little is known about MSCs of the
      head and neck region. We investigated cell biological properties with a potential
      impact on wound healing of 2 different tissue-resident MSC populations. METHODS:
      MSCs were isolated from human nasal mucosa (nmMSCs) and parotid gland (pgMSCs).
      Clonogenic potential, cell surface markers, cytokine secretion, chemokine
      receptor expression, mobility, and adhesion to extracellular matrix were examined
      in unstimulated and stimulated MSCs. RESULTS: NmMSCs had the higher clonogenic
      potential. PgMSCs showed a broader panel of chemokine receptor expression and
      displayed higher mobility, especially after challenge with bacterial
      lipopolysaccharide (LPS). NmMSCs were less mobile and showed increased LPS
      induced secretion of the inflammatory cytokine interleukin-8 (IL-8) compared with
      pgMSCs. CONCLUSION: These data highlight functional differences between tissue
      resident MSCs of the head and neck region, which may impact functional properties
      of these cells in response to trauma or infection.

PMID- 23152158
TI  - Clinical manifestations associated with Kawasaki disease shock syndrome in
      Mexican children.
AB  - Recently, there have been increasing reports of severe forms of Kawasaki disease
      (KD) associated with shock that have been managed in pediatric intensive care
      units. It has been suggested that KD is more severe in the Hispanic population.
      We conducted a study to determine the frequency of Kawasaki disease shock
      syndrome (KDSS) in our population and compared characteristics between patients
      with KD without shock and patients with KDSS. Data from 214 patients with KD
      treated in a tertiary pediatric hospital were collected during a 12-year period.
      We compared clinical and laboratory features of KD patients without shock and
      KDSS patients. Of 214 consecutive patients with KD, 11 (5 %) met the definition
      for KDSS. All of these patients received fluid resuscitation, seven (64 %)
      required inotropic treatment, and six (54 %), ventilatory support. On admission,
      seven of these patients (64 %) had an incomplete presentation of the disease,
      whereas in the group of patients without shock, the relative frequency of an
      incomplete presentation was 29 %. Twenty percent (3/11) of patients with KDSS
      presented giant coronary aneurysms versus none of 203 KD patients without shock
      (p = 0.001); myocardial infarction, 27 % (3/11), versus 1 % (2/203) (p = 0.001);
      and intravenous immunoglobulin (IVIG) resistance, 60 % (6/11), versus 12 %
      (24/203). Gastrointestinal manifestations in the acute phase occurred in 91 % of
      KDSS patients versus 30 % patients without shock (p = 0.001). CONCLUSION:
      Patients with KD presenting in shock seem to have an increase in gastrointestinal
      manifestations, incomplete presentation, IVIG resistance, and worse cardiac
      outcomes. Larger, prospective, multicentre studies should be carried out to
      corroborate these findings.

PMID- 23152159
TI  - Endothelial microparticle release is stimulated  in vitro  by purified IgG from
      patients with the antiphospholipid syndrome.
AB  - IgG antiphospholipid antibodies (aPL) exert direct effects on various cell types,
      contributing to the pathogenesis of thrombosis and pregnancy morbidity in
      patients with the antiphospholipid syndrome (APS). Some IgG samples from these
      patients activate endothelial cells (EC)  in vitro  as judged by surface
      expression of adhesion molecules such as E-selectin, which can promote
      thrombosis. Endothelial microparticles (EMP), which themselves are potentially
      prothrombotic, are released by activated EC. Though elevated circulating EMP
      levels have been reported in patients with APS, it is not known whether these EMP
      are released due to a direct effect of aPL on the cells. We tested the effect of
      purified polyclonal IgG from patients with APS (APS-IgG) and healthy controls (HC
      IgG) upon cultured human umbilical vein EC (HUVEC). HUVEC exposed to APS-IgG
      produced significantly more EMP than those exposed to HC-IgG (p=0.0036) and a
      greater proportion of these EMP carried surface E-selectin (6.2% +/- 4.0 for APS
      IgG vs.  3.4% +/- 2.0 for HC IgG, p=0.0172). This study therefore demonstrates
      that purified polyclonal APS-IgG can drive EMP release. We propose that EMP
      generation may be a useful measure of aPL-mediated pathogenic effects upon EC.

PMID- 23152160
TI  - Sampling, extraction and measurement of bacteria, endotoxin, fungi and
      inflammatory potential of settling indoor dust.
AB  - Selection of sampling device, sampling location and period are important first
      steps in the measurement of exposure to bioaerosols in indoor air. The steps
      following the sampling include treatment of samples and laboratory analysis. In
      this study, settling bacteria, endotoxin, fungi and serine protease have been
      measured in Danish homes using Electrostatic Dust Fall Collectors (EDCs). The
      effects of the presence of occupants, sampling on open surfaces versus in
      bookcases and treatment of samples have been studied. Concentrations of bacteria
      and endotoxin were significantly higher when occupants were at home than when
      they were absent. Across homes, higher concentrations of fungi were found in
      spring than in winter, as was the total inflammatory potential, while higher
      concentrations of protease were found in winter than in spring. The placement of
      the EDCs in bookcases versus on an open surface significantly affected the
      measured concentrations of bacteria and endotoxin. Direct extraction of EDC
      cloths caused a higher measured concentration of bacteria, fungi and serine
      protease than if EDC cloths were extracted post-storage at -20  degrees C.
      Extraction of EDC cloths caused an average of 51% and 58% extraction of bacteria
      and fungi respectively. In conclusion, EDCs should be placed on open surfaces
      during the sampling, how much occupants are present in their home during sampling
      and sampling season should be considered, EDC cloths should not be stored in a
      freezer before extraction of microorganisms, but extraction suspensions can be
      stored at -80  degrees C without affecting the number of microorganisms
      significantly.

PMID- 23152161
TI  - Mild hypertension: to treat or not to treat?

PMID- 23152162
TI  - Domperidone disaster: need for a single formulation?

PMID- 23152163
TI  - Hyponatremic-hypertensive syndrome: think of unilateral renal artery stenosis.
AB  - Hyponatremic hypertensive syndrome (HHS) is an uncommon disorder, in which
      hypertension is associated with profound hyponatremia. It is mostly encountered
      in adults with unilateral renal artery stenosis. Although renovascular
      hypertension is one of the commonest causes for severe hypertension in children,
      HHS is rarely reported in childhood. The authors report a 9-y old boy with
      hypertensive emergency and severe hyponatremia due to unilateral renal artery
      stenosis who was successfully managed by vascular stenting of the affected
      vessel. Prompt recognition of this disorder can be life-saving and can
      subsequently lead to appropriate referral and treatment as in the present case. 

PMID- 23152164
TI  - Influence of exogenously applied abscisic acid on carotenoid content and water
      uptake in flowers of the tea plant (Camellia sinensis).
AB  - BACKGROUND: Carotenoids are a major class of plant pigments and fulfill many
      functions in different organisms that either produce or consume them. Although
      the color of the stamina of tea (Camellia sinensis) flowers is clearly due to the
      presence of carotenoids, the carotenoid profile and content remain to be
      discovered. RESULTS: We investigated the carotenoid profile of tea flowers and
      determined changes in concentrations over the floral development. The flowers
      contained oxygenated xanthophylls such as neoxanthin, lutein and zeaxanthin, as
      well as the hydrocarbons beta-carotene and alpha-carotene. Flowers of the tea
      plant contain to vegetables comparable amounts of carotenoids. The content of 9'
      cis-epoxycarotenoids, which serve as abscisic acid precursors, as well as changes
      in concentration of abscisic acid were studied. The concentrations of carotenoids
      decreased whereas the abscisic acid content increased over the floral
      development. Exogenously applied S-abscisic acid affected water uptake, flower
      opening and carotenoid accumulation. CONCLUSION: In summary, this paper reports,
      for the first time, the carotenoid profile and content of tea flowers. The study
      revealed that carotenoids in tea flowers are an interesting target in respect of
      possible applications of tea flower extracts as well as biological functions of
      abscisic acid during floral development.

PMID- 23152165
TI  - Impaired hypoxic sensor Siah-1, PHD3, and FIH system in spinal motor neurons of
      an amyotrophic lateral sclerosis mouse model.
AB  - We recently reported spinal blood flow-metabolism uncoupling in the Cu/Zn
      superoxide dismutase 1 (SOD1)-transgenic (Tg) mouse model of amyotrophic lateral
      sclerosis (ALS), suggesting relative hypoxia in the spinal cord. However, the
      hypoxic stress sensor pathway in ALS has not been well studied. In the present
      work, we examined the temporal and spatial changes of hypoxic stress sensor
      proteins (Siah-1, PHD3, and FIH) following motor neuron (MN) degeneration in the
      spinal cord of normoxic ALS mice. The expression of Siah-1 and PHD3 proteins
      progressively increased in the surrounding glial cells of presymptomatic Tg mice
      (10 weeks, 10 weeks) compared with the large MN of the anterior horn. In
      contrast, a significant reduction in Siah-1 and PHD3 protein expression was
      evident in end-stage ALS mice (18 weeks, 18 weeks). Double-immunofluorescence
      analysis revealed PHD3 plus Siah-1 double-positive cells in the surrounding glia
      of symptomatic Tg mice (14-18 weeks), with no change in the large MNs. In
      contrast, FIH protein expression decreased in the surrounding glial cells of Tg
      mice at end-stage ALS (18 weeks). The present study suggests a partial loss in
      the neuroprotective response of spinal MNs in ALS results from a relative hypoxia
      through the Siah-1, PHD3, and FIH system under normoxic conditions. This response
      could be an important mechanism of neurodegeneration in ALS.

PMID- 23152166
TI  - Is acculturation associated with physical activity among female immigrants in
      Sweden?
AB  - BACKGROUND: Immigrant women in Sweden have lower levels of leisure time physical
      activity (LTPA) than Swedish-born women. The reasons are unclear, although
      acculturation has been suggested to play a role. METHODS: We used a cross
      sectional study design to investigate the association between LTPA and two
      indicators of acculturation: (i) language proficiency (ability to understand news
      reports on the radio and television) and (ii) age at the time of migration, and
      if there existed a modifying effect on these hypothesized associations. The study
      sample consisted of 1651 women, aged 18-65, living in Sweden and born in Finland,
      Chile or Iraq. A postal questionnaire (translated into the women's native
      language) was used to collect the variables. The International Physical Activity
      Questionnaire was used to assess LTPA. Data were collected in 2002-05 and
      analyzed in 2009-10. A partial-proportional odds model was used for the analysis.
      RESULTS: Increased language proficiency was associated with increased LTPA [odds
      ratio (OR) = 2.31, 95% confidence interval (CI) = 1.57-3.41]. Country of birth
      modified the association. Furthermore, younger age at migration was associated
      with increased LTPA (OR = 1.44, 95% CI = 1.01-2.03). CONCLUSIONS: Increased
      language proficiency has the potential to be an important health-promoting factor
      among immigrant women.

PMID- 23152167
TI  - Facilitation of fear extinction by the 5-HT(1A) receptor agonist tandospirone:
      possible involvement of dopaminergic modulation.
AB  - Fear extinction-based exposure treatment is an important component of
      psychotherapy for anxiety disorders such as posttraumatic stress disorder (PTSD).
      Recent studies have focused on pharmacological approaches combined with exposure
      therapy to augment extinction. In this study, we elucidated the therapeutic
      potential of the serotonin 1A (5-HT(1A) ) receptor agonist tandospirone compared
      with the effects of the N-methyl-D-aspartate partial agonist D-cycloserine (DCS),
      focusing on the possible involvement of dopaminergic mechanisms. We used a rat
      model of juvenile stress [aversive footshock (FS)] exposure during the third
      postnatal week (3wFS). The 3wFS group exhibited extinction deficit reflected in
      sustained fear-related behavior and synaptic dysfunction in the hippocampal CA1
      field and medial prefrontal cortex (mPFC), which are responsible for extinction
      processes. Tandospirone administration (5 mg/kg, i.p.) before and after the
      extinction trials ameliorated both the behavioral deficit and synaptic
      dysfunction, i.e., synaptic efficacy in the CA1 field and mPFC associated with
      extinction training and retrieval, respectively, was potentiated in the
      tandospirone-treated 3wFS group. Extracellular dopamine release in the mPFC was
      increased by extinction retrieval in the non-FS control group. This facilitation
      was not observed in the 3wFS group; however, tandospirone treatment increased
      cortical dopamine levels after extinction retrieval. DCS (15 mg/kg, i.p.) also
      ameliorated the extinction deficit in the 3wFS group, but impaired extinction in
      the non-FS control group. These results suggest that tandospirone has therapeutic
      potential for enhancing synaptic efficacy associated with extinction processes by
      involving dopaminergic mechanisms. Pharmacological agents that target cortical
      dopaminergic systems may provide new insights into the development of therapeutic
      treatments of anxiety disorders, including PTSD.

PMID- 23152169
TI  - Transposition of the hepatic artery as a salvage procedure for an aortic
      pseudoaneurysm after liver transplantation.

PMID- 23152168
TI  - Different mechanisms lead to convergence of reproductive strategies in two
      lacertid lizards (Takydromus wolteri and Eremias argus).
AB  - Life history traits may vary within and among species. Rarely, however, are both
      variations examined concurrently to identify the life history adaptation. We
      found that female body size, offspring number and size, and incubation period
      showed convergent evolution in two lacertid lizards (Takydromus wolteri and
      Eremias argus) that occur sympatrically in high-latitude and low-latitude
      localities. Females from the high-latitude population were larger and produced
      larger clutches than those from the low-latitude population. In both species, the
      incubation period was shorter for the high-latitude population than for the low
      latitude population. However, the physiological mechanism underlying the shorter
      incubation period differed between the species. These results suggest that: (1)
      sympatric lizards may adopt similar reproductive strategies in response to their
      common environments, and (2) embryonic development of the two species follows
      different pathways for adaptation to low temperatures. This study highlights the
      importance of understanding the adaptive evolution of life history in response to
      environmental changes at the embryonic life stages.

PMID- 23152172
TI  - [Results from the pilot project of the Techniker Krankenkasse (TK) 'quality
      monitoring in outpatient psychotherapy': the evaluators' perspective].
AB  - This is the first study to evaluate a quality assurance and feedback tool with
      regard to its practical feasibility in routine care and within the German health
      insurance system. This paper summarizes the evaluators' perspective on issues
      regarding the representativeness of the sample, consequences for therapy length
      and central assumptions and concepts of the project. The evaluation team comments
      on the paper "Pilot project of the Techniker-Krankenkasse - A comment from the
      perspective of the academic advisory council".

PMID- 23152174
TI  - Field-deployable and near-real-time optical microfluidic biosensors for single
      oocyst-level detection of Cryptosporidium parvum from field water samples.
AB  - Cryptosporidium spp. is an obligate, parasitic protozoan that is difficult to
      detect and causes diarrhea in healthy adults while potentially causing death in
      the immunocompromised and children. Its treatment options are few and treat the
      symptoms, not the actual parasite. Current methods of detection are inefficient
      and rely too heavily upon laboratory sample preparations and technician skill,
      including differential staining, negative staining, and immunofluorescence
      methods [especially U.S. Environmental Protection Agency (EPA) Method 1623].
      These assays can take from hours to days and require a laboratory environment. In
      this work, we demonstrated the microbead immunoagglutination assay combined with
      Mie scatter detection in a microfluidic device to provide a field-deployable and
      near-real-time alternative to the laboratory-based method (especially EPA Method
      1623). Two main challenges were the relatively big diameter of Cryptosporidium
      oocysts (5-6 MUm) and the contaminants in field water samples that negatively
      affected the immunoagglutination and its scatter detection. We used 4 min
      sonication to liberate Cryptosporidium oocyst wall proteins (COWP), which was
      previously used to inactivate Cryptosporidium oocysts. As for the contaminants,
      we optimized the microbead diameter (920 nm) and the wavelength of incident light
      (375 nm) to find the angle of scatter detection (45 degrees ) where the Mie
      scatter from immunoagglutinated microbeads was maximum and the background scatter
      from contaminants was minimum. This enabled the sub-single-oocyst-level detection
      despite the fact that only a very small volume of water sample (15 MUL) was
      introduced to the microfluidic biosensor. When combined with
      filtration/concentration, this method is able to detect <=1 oocyst per large
      volume of water, comparable to or potentially better than the EPA method 1623,
      while effectively reducing the time and labor necessary for staining and
      microscopic analysis. For faster, near-real-time assays, filtration/concentration
      may not be used, where the detection limit was 1-10 oocysts per mL with the total
      assay time of 10 min including the 4 min sonication time. The linear range of
      assay was over 5 orders of magnitude. The final device was compact and had the
      potential to be used in field situations, and required less technical expertise
      and/or training compared to the other methods.

PMID- 23152173
TI  - Multiphasic contrast-enhanced MRI: single-slice versus volumetric quantification
      of tumor enhancement for the assessment of renal clear-cell carcinoma fuhrman
      grade.
AB  - PURPOSE: To assess the association between clear-cell carcinoma pathology grade
      at nephrectomy and magnetic resonance imaging (MRI) tumor enhancement. MATERIALS
      AND METHODS: The Institutional Review Board approved this retrospective study and
      waived the informed consent requirement. In all, 32 patients underwent multiphase
      contrast-enhanced MRI prior to nephrectomy. MRI tumor enhancement was measured
      using two approaches: 1) the most enhancing portion of the tumor on a single
      slice and 2) volumetric analysis of enhancement in the entire tumor. Associations
      between pathological grade, tumor size, and enhancement were evaluated using the
      Kruskal-Wallis test and generalized logistic regression models. RESULTS: No
      significant association between pathology grade and enhancement was found when
      measurements were made on a single slice. When measured in the entire tumor,
      significant associations were found between higher pathology grades and lower
      mean, median, top 10%, top 25%, and top 50% tumor enhancement (P < 0.001-0.002).
      On multivariate analysis the association between grade and enhancement remained
      significant (P = 0.041-0.043), but tumor size did not make an additional
      contribution beyond tumor enhancement alone in differentiating between tumor
      grades. CONCLUSION: There is significant association between tumor grade and
      enhancement, but only when measured in the entire tumor and not on the most
      enhancing portion on a single slice.

PMID- 23152176
TI  - Bezafibrate to prevent relapsing pancreatitis in WAGR syndrome.
AB  - Recurrent episodes of acute, severe pancreatitis are a feature of the rare WAGR
      congenital anomaly syndrome. Although pancreatitis is well recognised as a life
      threatening association of WAGR syndrome, treatment to prevent pancreatitis is
      not recommended. We report the successful prevention of hypertriglyceridaemia
      associated relapsing pancreatitis in a child with WAGR syndrome with Bezafibrate.
      In addition to dietary fat restriction, Bezafibrate may be a useful therapeutic
      adjunct in WAGR related relapsing pancreatitis.

PMID- 23152177
TI  - Delayed sciatic nerve palsy following resurfacing hip arthroplasty caused by
      metal debris.
AB  - The rapid rise in the incidence of failed metal-on-metal hip articulations in
      recent years has led to many patients requiring complex revision surgery. These
      failed metal prostheses may produce local metallic debris, which promotes both
      local and systemic adverse effects. We report an unusual case of failed metal-on
      metal resurfacing hip arthroplasty presenting with ipsilateral buttock pain and
      foot drop 6 months after surgery. After thorough investigations, the metal-on
      metal bearing was revised to a metal-on-polyethylene total hip replacement. This
      resulted in marked improvement in the systemic symptoms, inflammatory marke and
      metal ion levels postoperatively. However, neither clinical nor
      neurophysiological sciatic nerve recovery followed. The patient eventually
      required tendon transfer surgery for her persistent foot drop.

PMID- 23152178
TI  - FNA diagnosis of malignant melanoma-recurrent and metastatic disease.
AB  - We present a case of a 60-year-old woman with multiple right axillary swellings.
      Patient had a history of lump with pigmentation over back for which she was
      operated upon. There was also a nodule over resected scar on back. A final
      diagnosis of malignant melanoma (recurrent and metastatic to axillary lymph
      nodes) was rendered with the help of fine-needle aspiration cytology (FNAC).
      Malignant melanomas are the most lethal of cancers of the skin and are notorious
      for the great variability of cytological presentation. We discuss the role of
      FNAC in early diagnosis and prognostication of recurrent and metastatic disease.

PMID- 23152179
TI  - The primary percutaneous coronary intervention for acute anterior myocardial
      infarction in a middle-aged male patient with bilateral coronary artery to
      pulmonary artery fistulas.
AB  - A 38-year-old man admitted to emergency department with 2 h of typical substernal
      chest pain, shortness of breath and nausea. The ECG revealed sinus rhythm with a
      3 mm ST elevation in precordial leads V1-V6. The coronary angiography revealed
      acute total occlusion in left anterior descending artery (LAD) with normal
      circumflex and right coronary artery (RCA) along with bilateral fistulas arising
      from the proximal LAD and ostial RCA draining into the main pulmonary artery.
      Therefore, primary percutaneous coronary intervention and bare metal stent
      implantation was performed to culprit LAD lesion. The electrocardiographically
      gated 64-slice multidetector-row CT showed two large, tortuous abnormal vessels
      which arose from the both ostial part of the RCA and LAD draining into the main
      pulmonary artery. We report an unusual case of bilateral coronary artery to
      pulmonary artery fistulas leading to acute anterior myocardial infarction in a
      middle-aged male patient.

PMID- 23152180
TI  - Successful laparoscopic investigation and resection of solitary colonic
      metastasis from breast cancer (with video).
AB  - Metastasis to gastrointestinal tract from breast cancer is an uncommon situation.
      We report a case of a 52-year-old woman who had a mastectomy for solid-tubular
      carcinoma of the breast 16 years ago and bilateral salpingo-oophorectomy for
      metastatic ovarian tumours 5 years ago, was incidentally found to have colonic
      metastatic tumour detected by positron emission tomography/CT (PET/CT) during
      follow-up. After identifying a definite location of the tumour in the ascending
      colon under laparoscopic investigation, laparoscopy-assisted partial colectomy
      was successfully performed. Histopathology of the resected specimen showed it to
      be metastasis from solid-tubular carcinoma of the breast. We should be aware that
      breast cancer can metastasise to the gastrointestinal tract even after the long
      interval from initial therapy. An index of high suspicion and detailed assessment
      is mandatory to make a correct diagnosis and following less invasive surgical
      treatment.

PMID- 23152181
TI  - Hypokalaemia: common but not always benign. Severe, persistent hypokalaemia
      secondary to ectopic ACTH from a carcinoid tumour.
AB  - Hypokalaemia is a common and often benign observation. There is usually an
      obvious underlying cause for the anomaly. However, hypokalaemia can very rarely
      be the sole presentation of a more sinister disease. A high index of suspicion
      and a systematic approach are therefore required to avoid delays in the
      management, especially in the context of presentation to a medical team. We
      present a case of a patient with severe and persistent hypokalaemia due to
      ectopic adrenocorticotropic hormone (ACTH) secretion secondary to a carcinoid
      tumour. The case report is followed by a brief discussion on the approach to the
      management of hypokalaemia and additional tests to confirm ectopic ACTH.

PMID- 23152182
TI  - Isolated cystic cervical oesophageal duplication: a rare congenital anomaly.
AB  - Oesophageal duplication is a rare congenital anomaly. The cystic form is the
      usual presentation of the duplication, found predominantly in the lower third.
      Less than 20 cases of isolated cystic oesophageal duplication in the cervical
      region have been reported till date in the English literature. We are reporting
      this case because of its rarity.

PMID- 23152183
TI  - DRESS syndrome and thrombotic thrombocytopaenic purpura: are they related?
AB  - A middle-aged man diagnosed with a drug reaction with eosinophilia and systemic
      symptom (DRESS) syndrome, secondary to phenytoin use, subsequently developed
      thrombotic thrombocytopaenic purpura. The patient improved with steroids and
      plasmapheresis. Their diagnosis can be challenging, and an early recognition and
      treatment are critical owing to their high mortality rates. Both diseases are
      thought to be of an autoimmune origin, and a potential relationship between them
      led to the consideration of the DRESS syndrome as an aetiology for thrombotic
      thrombocytopaenic purpura in this case. We concluded that two possibilities
      exist: some type of antibody developed during the clinical presentation of DRESS
      syndrome and subsequently resulted in an inhibition of a disintegrin and
      metalloproteinase with a thrombospondin type-1 motif, member 13 (ADAMTS13)
      leading to thrombotic thrombocytopaenic purpura, or perhaps this patient's
      autoimmune predisposition to thrombotic thrombocytopaenic purpura contributed to
      the drug reaction.

PMID- 23152184
TI  - PGI chicory (Cichorium intybus L.) traceability by means of HRMAS-NMR
      spectroscopy: a preliminary study.
AB  - BACKGROUND: Analytical traceability of PGI and PDO foods (Protected Geographical
      Indication and Protected Denomination Origin respectively) is one of the most
      challenging tasks of current applied research. RESULTS: Here we proposed a
      metabolomic approach based on the combination of (1)H high-resolution magic angle
      spinning-nuclear magnetic resonance (HRMAS-NMR) spectroscopy with multivariate
      analysis, i.e. PLS-DA, as a reliable tool for the traceability of Italian PGI
      chicories (Cichorium intybus L.), i.e. Radicchio Rosso di Treviso and Radicchio
      Variegato di Castelfranco, also known as red and red-spotted, respectively. The
      metabolic profile was gained by means of HRMAS-NMR, and multivariate data
      analysis allowed us to build statistical models capable of providing clear
      discrimination among the two varieties and classification according to the
      geographical origin. CONCLUSION: Based on Variable Importance in Projection
      values, the molecular markers for classifying the different types of red
      chicories analysed were found accounting for both the cultivar and the place of
      origin.

PMID- 23152185
TI  -  Forever young?  Exploring the link between rapamycin, longevity and cancer.

PMID- 23152186
TI  - Arsenic activates endothelin-1 Gi protein-coupled receptor signaling to inhibit
      stem cell differentiation in adipogenesis.
AB  - Dysfunctional lipid and glucose metabolism contribute to metabolic syndrome-a
      major public health concern that enhances cardiovascular disease risk. Arsenic
      (As(III)) exposure may increase metabolic syndrome and cardiovascular disease
      risk by impairing adipose tissue differentiation, function, and insulin
      sensitivity through pathogenic mechanisms that remain unclear. We hypothesized
      that As(III) signals through the Pertussis toxin (Ptx) sensitive, Gi protein
      coupled receptor (GPCR) to impair adipogenesis, as previously demonstrated for
      its stimulation of vascular oxidant generation, angiogenesis, and remodeling.
      Because both As(III) and GPCR ligands inhibit progenitor cell differentiation
      into adipocytes, we investigated the hypothesis in a model of low-passage human
      mesenchymal stem cells (hMSC). As(III) (0.1-1.0 uM) suppressed
      dexamethasone/insulin-induced hMSC adipogenesis, as indicated by decreased
      transcriptional promoters of differentiation, decreased fat droplet formation,
      and decreased expression of differentiated adipocyte markers, such as adiponectin
      and perilipin. Preincubating hMSC with Ptx prevented 90% of the suppressive
      effect of As(III). Selective competitive antagonists of Gi-coupled endothelin-1
      type A and B receptors were ~60% effective in blocking As(III) inhibition and
      combination of antagonists to both receptors were 85% effective. In contrast,
      antagonists to the sphingosine-1-phosphate type 1 receptor (previously shown to
      mediate As(III) vascular effects) or the angiotensin II type 1 receptor were
      ineffective in blocking As(III) effects. These studies suggest a majority of
      arsenic-inhibited adipocyte differentiation, and metabolism requires endothelin-1
      GPCRs and that As(III) effects on GPCR signaling are tissue and context specific.
      This may represent a significant mechanism for the contribution of arsenic
      exposure to increased metabolic and cardiovascular diseases.

PMID- 23152187
TI  - Expression of human CAR splicing variants in BAC-transgenic mice.
AB  - The nuclear receptor constitutive androstane receptor (CAR) is a key regulator
      for drug metabolism in liver. Human CAR (hCAR) transcripts are subjected to
      alternative splicing. Some hCAR splicing variants (SVs) have been shown to encode
      functional proteins by reporter assays. However, in vivo research on the activity
      of these hCAR SVs has been impeded by the absence of a valid model. This study
      engineered an hCAR-BAC-transgenic (hCAR-TG) mouse model by integrating the 8.5
      kbp hCAR gene as well as 73-kbp upstream and 91-kbp downstream human genomic DNA
      into the genome of CAR-null mice. A series of experiments demonstrate that (1)
      the expression of major hCAR mRNA SVs, SV0-4, in livers of hCAR-TG mice is
      comparable to that in human livers; (2) the hCAR SVs are predominantly expressed
      in liver, which resembles the tissue distribution of CAR in humans, but diverges
      from that in mice; and (3) major hCAR mRNA SVs increase markedly in postnatal
      livers of hCAR-TG mice, which mimics the ontogeny of CAR mRNA in humans. Thus,
      the transgene likely contains all the functional regulatory elements controlling
      proper spatial and temporal expression of the hCAR gene. Moreover, hCAR-TG mice
      respond to the hCAR-specific agonist 6-(4-chlorophenyl)imidazo[2,1-b]
      [1,3]thiazole-5-carbaldehyde O-(3,4-dichlorobenzyl)oxime instead of the mouse CAR
      agonist 1,4-bis[2-(3,5-dichloropyridyloxy)]benzene, as well as the common CAR
      activator, phenobarbital, suggesting that hCAR is fully functional in livers of
      transgenic mice. In summary, the hCAR-TG mice developed by this study represent a
      valid model for studying in vivo function and regulation of hCAR and its splicing
      variants.

PMID- 23152188
TI  - In vivo tungsten exposure alters B-cell development and increases DNA damage in
      murine bone marrow.
AB  - High environmental tungsten levels were identified near the site of a childhood
      pre-B acute lymphoblastic leukemia cluster; however, a causal link between
      tungsten and leukemogenesis has not been established. The major site of tungsten
      deposition is bone, the site of B-cell development. In addition, our in vitro
      data suggest that developing B lymphocytes are susceptible to tungsten-induced
      DNA damage and growth inhibition. To extend these results, we assessed whether
      tungsten exposure altered B-cell development and induced DNA damage in vivo. Wild
      type mice were exposed to tungsten in their drinking water for up to 16 weeks.
      Tungsten concentration in bone was analyzed by inductively coupled plasma mass
      spectrometry and correlated with B-cell development and DNA damage within the
      bone marrow. Tungsten exposure resulted in a rapid deposition within the bone
      following 1 week, and tungsten continued to accumulate thereafter albeit at a
      decreased rate. Flow cytometric analyses revealed a transient increase in mature
      IgD(+) B cells in the first 8 weeks of treatment, in animals of the highest and
      intermediate exposure groups. Following 16 weeks of exposure, all tungsten groups
      had a significantly greater percentage of cells in the late pro-/large pre-B
      developmental stages. DNA damage was increased in both whole marrow and isolated
      B cells, most notably at the lowest tungsten concentration tested. These findings
      confirm an immunological effect of tungsten exposure and suggest that tungsten
      could act as a tumor promoter, providing leukemic "hits" in multiple forms to
      developing B lymphocytes within the bone marrow.

PMID- 23152190
TI  - Use of micropatterned cocultures to detect compounds that cause drug-induced
      liver injury in humans.
AB  - Because drug-induced liver injury (DILI) remains a major reason for late-stage
      drug attrition, predictive assays are needed that can be deployed throughout the
      drug discovery process. Clinical DILI can be predicted with a sensitivity of ~50%
      and a false positive (FP) rate of ~5% using 24-h cultures of sandwich-cultured
      primary human hepatocytes and imaging of four cell injury endpoints (Xu et al.,
      2008). We hypothesized that long-term drug dosing in a functionally stable model
      of primary hepatocytes (micropatterned cocultures [MPCCs]) could provide for
      increased predictivity over short-term dosing paradigms. We used MPCCs with
      either primary human or rat hepatocytes to understand possible species
      differences along with standard endpoints (glutathione levels, ATP levels,
      albumin, and urea secretion) to test 45 drugs either known or not known to cause
      clinical DILI. Human MPCCs correctly detected 23 of 35 compounds known to cause
      DILI (65.7% sensitivity), with a FP rate of 10% for the 10 negative compounds
      tested. Rat MPCCs correctly detected 17 of 35 DILI compounds (48.6% sensitivity)
      and had a higher FP rate than human MPCCs (20 vs. 10%). For an additional 19
      drugs with the most DILI concern, human MPCCs displayed a sensitivity of 100%
      when at least two hepatocyte donors were used for testing. Furthermore, MPCCs
      were able to detect relative clinical toxicities of structural drug analogs. In
      conclusion, MPCCs showed superiority over conventional short-term cultures for
      predictions of clinical DILI, and human MPCCs were more predictive for human
      liabilities than their rat counterparts.

PMID- 23152189
TI  - 2,3,7,8-Tetrachlorodibenzo-p-dioxin-mediated production of reactive oxygen
      species is an essential step in the mechanism of action to accelerate human
      keratinocyte differentiation.
AB  - Chloracne is commonly observed in humans exposed to 2,3,7,8-tetrachlorodibenzo-p
      dioxin (TCDD); yet, the mechanism of toxicity is not well understood. Using
      normal human epidermal keratinocytes, we investigated the mechanism of TCDD
      mediated enhancement of epidermal differentiation by integrating functional
      genomic, metabolomic, and biochemical analyses. TCDD increased the expression of
      40% of the genes of the epidermal differentiation complex found on chromosome
      1q21 and 75% of the genes required for de novo ceramide biosynthesis. Lipid
      analysis demonstrated that eight of the nine classes of ceramides were increased
      by TCDD, altering the ratio of ceramides to free fatty acids. TCDD decreased the
      expression of the glucose transporter, SLC2A1, and most of the glycolytic
      transcripts, followed by decreases in glycolytic intermediates, including
      pyruvate. NADH and Krebs cycle intermediates were decreased, whereas NAD(+) was
      increased. Mitochondrial glutathione (GSH) reductase activity and the
      GSH/glutathione disulfide ratio were decreased by TCDD, ultimately leading to
      mitochondrial dysfunction, characterized by decreased inner mitochondrial
      membrane potential and ATP production, and increased production of the reactive
      oxygen species (ROS), hydrogen peroxide. Aryl hydrocarbon receptor (AHR)
      antagonists blocked the response of many transcripts to TCDD, and the endpoints
      of decreased ATP production and differentiation, suggesting regulation by the
      AHR. Cotreatment of cells with chemical antioxidants or the enzyme catalase
      blocked the TCDD-mediated acceleration of keratinocyte cornified envelope
      formation, an endpoint of terminal differentiation. Thus, TCDD-mediated ROS
      production is a critical step in the mechanism of this chemical to accelerate
      keratinocyte differentiation.

PMID- 23152191
TI  - Delta9-tetrahydrocannabinol impairs the inflammatory response to influenza
      infection: role of antigen-presenting cells and the cannabinoid receptors 1 and
      2.
AB  - Delta(9)-tetrahydrocannabinol (Delta(9)-THC) has potent immune modulatory
      properties and can impair pathogen-induced immune defenses, which in part have
      been attributed to ligation of the cannabinoid receptors 1 (CB(1)) and 2 (CB(2)).
      Most recently, dendritic cells (DC) were identified for their potential to
      enhance influenza-induced immunopathology in mice lacking CB(1) and CB(2) (CB(1)
      (-/-)CB(2) (-/-)). This study focused on the modulation of the inflammatory
      immune response to influenza by Delta(9)-THC and the role of CB(1) and/or CB(2)
      as receptor targets for Delta(9)-THC. C57Bl/6 (wild type) and CB(1) (-/-)CB(2) (
      /-) mice were administered Delta(9)-THC (75 mg/kg) surrounding the intranasal
      instillation of A/PR/8/34 influenza virus. Three days post infection (dpi),
      Delta(9)-THC broadly decreased expression levels of mRNA induced by the innate
      immune response to influenza, suppressed the percentage of interferon-gamma (IFN
      gamma)-producing CD4(+) and interleukin-17-producing NK1.1(+) cells, and reduced
      the influx of antigen-presenting cells (APC), including inflammatory myeloid
      cells and monocytes/macrophages, into the lung in a CB(1)- and/or CB(2)-dependent
      manner. Delta(9)-THC had little effect on the expression of CD86, major
      histocompatibility complex I (MHC I), and MHC II by APC isolated from the lung.
      In vitro studies demonstrated that lipopolysaccharide (LPS)-induced maturation
      was suppressed by Delta(9)-THC in bone marrow-derived DC (bmDC). Furthermore,
      antigen-specific IFN-gamma production by CD8(+) T cells after coculture was
      reduced by Delta(9)-THC treatment of bmDC in a CB(1)- and/or CB(2)-dependent
      manner. Collectively, these studies suggest that Delta(9)-THC potently suppresses
      myeloid cell immune function, in a manner involving CB(1) and/or CB(2), thereby
      impairing immune responses to influenza infection.

PMID- 23152192
TI  - Cerebrolysin modulates pronerve growth factor/nerve growth factor ratio and
      ameliorates the cholinergic deficit in a transgenic model of Alzheimer's disease.
AB  - Alzheimer's disease (AD) is characterized by degeneration of neocortex, limbic
      system, and basal forebrain, accompanied by accumulation of amyloid-beta and
      tangle formation. Cerebrolysin (CBL), a peptide mixture with neurotrophic-like
      effects, is reported to improve cognition and activities of daily living in
      patients with AD. Likewise, CBL reduces synaptic and behavioral deficits in
      transgenic (tg) mice overexpressing the human amyloid precursor protein (hAPP).
      The neuroprotective effects of CBL may involve multiple mechanisms, including
      signaling regulation, control of APP metabolism, and expression of neurotrophic
      factors. We investigate the effects of CBL in the hAPP tg model of AD on levels
      of neurotrophic factors, including pro-nerve growth factor (NGF), NGF, brain
      derived neurotrophic factor (BDNF), neurotropin (NT)-3, NT4, and ciliary
      neurotrophic factor (CNTF). Immunoblot analysis demonstrated that levels of pro
      NGF were increased in saline-treated hAPP tg mice. In contrast, CBL-treated hAPP
      tg mice showed levels of pro-NGF comparable to control and increased levels of
      mature NGF. Consistently with these results, immunohistochemical analysis
      demonstrated increased NGF immunoreactivity in the hippocampus of CBL-treated
      hAPP tg mice. Protein levels of other neurotrophic factors, including BDNF, NT3,
      NT4, and CNTF, were unchanged. mRNA levels of NGF and other neurotrophins were
      also unchanged. Analysis of neurotrophin receptors showed preservation of the
      levels of TrKA and p75(NTR) immunoreactivity per cell in the nucleus basalis.
      Cholinergic cells in the nucleus basalis were reduced in the saline-treated hAPP
      tg mice, and treatment with CBL reduced these cholinergic deficits. These results
      suggest that the neurotrophic effects of CBL might involve modulation of the pro
      NGF/NGF balance and a concomitant protection of cholinergic neurons.

PMID- 23152193
TI  - Mediterranean climate patterns and wine quality in North and Central Italy.
AB  - Results show that the year-to-year quality variation of wines produced in North
      and Central Italy depends on the large-scale climate variability, and that the
      wine quality improvement in the last four decades is partially due to an increase
      of temperature and to a decrease of precipitation in West and Central
      Mediterranean Europe (WME; CME). In addition, wine quality is positively
      correlated with air temperature throughout the entire active period of the
      grapevine, weakly negatively correlated with precipitation in spring, and well
      negatively correlated in summer and fall. The month-to-month composites of the
      NAO anomaly show that, in years of good quality wine, this anomaly is negative in
      late spring, oscillates around zero in summer, and is positive in early fall;
      while, in years of bad quality wine, it is positive in late spring and summer,
      and negative in early fall, i.e. its polarity has an opposite sign in spring and
      fall in good versus bad years. The composite seasonal maps show that good wines
      are produced when the spring jet stream over the Atlantic diverts most of the
      weather perturbations towards North Europe, still providing a sufficient amount
      of rainwater to CME; when summer warming induced by southerly winds is balanced
      by the cooling induced by westerly winds; and when a positive geopotential
      anomaly over WME shelters CME from fall Atlantic storms. Bad quality wines are
      produced when the jet stream favors the intrusion of the Atlantic weather
      perturbations into the Mediterranean. Results suggest that atmospheric pattern
      persistencies can be used as precursors for wine quality forecast. 

PMID- 23152195
TI  - Myosin isoform fiber type and fiber size in the tail of the Virginia opossum
      (Didelphis virginiana).
AB  - Muscle fiber type is a well studied property in limb muscles, however, much less
      is understood about myosin heavy chain (MHC) isoform expression in caudal muscles
      of mammalian tails. Didelphid marsupials are an interesting lineage in this
      context as all species have prehensile tails, but show a range of tail-function
      depending on either their arboreal or terrestrial locomotor habits. Differences
      in prehensility suggest that MHC isoform fiber types may also be different, in
      that terrestrial opossums may have a large distribution of oxidative fibers for
      object carrying tasks instead of faster, glycolytic fiber types expected in
      mammals with long tails. To test this hypothesis, MHC isoform fiber type and
      their regional distribution (proximal/transitional/distal) were determined in the
      tail of the Virginia opossum (Didelphis virginiana). Fiber types were determined
      by a combination of myosin-ATPase histochemistry, immunohistochemistry, and SDS
      PAGE. Results indicate a predominance of the fast MHC-2A and -2X isoforms in each
      region of the tail. The presence of two fast isoforms, in addition to the slow
      MHC-1 isoform, was confirmed by SDS-PAGE analysis. The overall MHC isoform fiber
      type distribution for the tail was: 25% MHC-1, 71% MHC-2A/X hybrid, and 4% MHC
      1/2A hybrid. Oxidative MHC-2A/X isoform fibers were found to be relatively large
      in cross-section compared to slow, oxidative MHC-1 and MHC-1/2A hybrid fibers. A
      large percentage of fast MHC-2A/X hybrids fibers may be suggestive of an
      evolutionary transition in MHC isoform distribution (fast-to-slow fiber type) in
      the tail musculature of an opossum with primarily a terrestrial locomotor habit
      and adaptive tail-function.

PMID- 23152196
TI  - Sampling of herbicides in streams during flood events.
AB  - In stream water xenobiotics usually occur as pulses in connection with floods
      caused by surface run-off and tile drainage following precipitation events. In
      streams located in small agricultural catchments we monitored herbicide
      concentrations during flood events by applying an intensive sampling programme of
      1/2 h intervals for 7 h. In contrast to grab sampling under non-flood conditions,
      clearly elevated concentrations were recorded during the floods, and pulses
      varying in occurrence, duration and concentration were recorded. Pulses of
      recently applied herbicides were the most prominent, but also agricultural
      herbicides used in previous seasons caused pulses in the streams. Asynchronism of
      chemographs may be related to the characteristics of the compounds as well as
      their transport pathways and transformation in compartments between the source
      and the point of sampling in the stream. Thus, the occurrence of chemographs is
      difficult to predict, which ought to be taken into account when designing a
      sampling strategy. Even though the chemographs of herbicides and their
      transformation products (glyphosate and aminomethylphosphonic acid (AMPA) as well
      as terbuthylazine and desethylterbuthylazine) seem to be synchronous, their
      occurrence may still be difficult to predict. It is evident that grab sampling
      under non-flood conditions yields insufficient information on the dynamics of
      occurrence of herbicides in stream water, both with respect to environmental
      effects and the calculation of the load to a recipient. In conclusion, the design
      of a sampling strategy regarding herbicides in stream waters should adequately
      consider the aim of the investigation.

PMID- 23152194
TI  - Prevalence of asthma symptoms in schoolchildren, and climate in west European
      countries: an ecologic study.
AB  - The aim of the present study was to estimate the associations between the
      prevalence of asthma symptoms in schoolchildren and meteorological variables in
      west European countries that participated in the International Study of Asthma
      and Allergies in Children (ISAAC), Phase III 1997-2003. An ecologic study was
      carried out. The prevalence of asthma was obtained from this study from 48
      centers in 14 countries, and meteorological variables from those stations closest
      to ISAAC centers, together with other socioeconomic and health care variables.
      Multilevel mixed-effects linear regression models were used. For schoolchildren
      aged 6-7 years, the prevalence rate of asthma decreased with an increase in mean
      annual sunshine hours, showed a positive association with rainy weather, and warm
      temperature, and a negative one with relative humidity and physician density
      (PD). Current wheeze prevalence was stronger in autumn/winter seasons and
      decreased with increasing PD. Severe current wheeze decreased with PD. For
      schoolchildren aged 13-14 years, the prevalence rates of asthma and current
      wheeze increased with rainy weather, and these rates decreased with increased PD.
      Current wheeze, as measured by a video questionnaire, was inversely associated
      with sunny weather, and nurse density. Severe current wheeze prevalence was
      stronger during autumn/winter seasons, decreased with PD, and indoor chlorinated
      public swimming pool density, and increased with rainy weather. Meteorological
      factors, including sunny and rainy weather, and PD may have some effect on the
      prevalence rates of asthma symptoms in children from west European countries. 

PMID- 23152197
TI  - Mitochondrial plasticity of the hippocampus in a genetic rat model of depression
      after antidepressant treatment.
AB  - Depressive disorders and the treatment thereof have been associated with a number
      of neuroplastic events, such as neurogenesis and synaptic remodeling in discrete
      areas of the brain. The associations of these events in changes regarding the
      energy supply have not been investigated. Here, we investigated the changes in
      mitochondrial plasticity and its correlation to morphological alterations of
      neuroplasticity in the hippocampus, both associated with a depressive phenotype,
      and after treatment, with antidepressant imipramine. Design-based stereological
      methods were used to estimate the number and volume of mitochondria in CA1 of the
      hippocampus in two different strains of rats, the Sprague-Dawley (SD) and
      Flinders rats, which display a genetic susceptibility to depressive behavior, the
      Flinders-sensitive line (FSL) and their corresponding controls, the Flinders
      resistant line (FRL). Results showed a significantly reduced number of
      mitochondria in CA1, which was significantly smaller in the untreated FSL saline
      group compared to the FRL group. However, the mean volume of mitochondria was
      significantly larger in the FSL saline group compared to the FRL saline group.
      Following treatment, the FSL imipramine group showed a significant increase in
      the number of mitochondria compared to the FSL saline group. Treatment with
      imipramine in the SD rats did not induce significant differences in the number of
      mitochondria. Our results indicate that depression may be related to impairments
      of mitochondrial plasticity in the hippocampus and antidepressant treatment may
      counteract with the structural impairments. Moreover, the changes in
      mitochondrial morphology and number are a consistent feature of neuroplasticity.

PMID- 23152198
TI  - Prophylactic administration of prothrombin complex concentrates for congenital
      prothrombin deficiency with a novel frameshift mutation, prothrombin saitama.
AB  - Prothrombin (Factor II, FII) deficiency is an extremely rare autosomal recessive
      condition with an estimated incidence of 1:2 million. As severe and life
      threatening bleeding is rare in FII deficiency, on demand therapy with
      administration of prothrombin complex concentrates (PCCs) or fresh frozen plasma
      is generally performed, and prophylactic therapy for FII deficiency has been
      reported in only three cases. Thus, its optimal dosage and schedule has remained
      uncertain. Here we report a case of severe prothrombin deficiency with a novel
      frameshift mutation of the F2 gene, who was started on prophylactic
      administration.

PMID- 23152199
TI  - Topical preparations for preventing stretch marks in pregnancy.
AB  - BACKGROUND: Striae gravidarum (stretch marks developing during pregnancy) occur
      in 50% to 90% of women. They appear as red or purple lines or streaks that fade
      slowly to leave pale lines or marks on the skin. The abdomen, breasts and thighs
      are commonly affected. The exact cause of stretch marks is unclear and no
      preparation has yet been shown to be effective in preventing the development of
      stretch marks. They are a source of significant anxiety for women, impacting on
      their quality of life. OBJECTIVES: To assess the effects of topical preparations
      on the prevention of stretch marks in pregnancy. SEARCH METHODS: We searched the
      Cochrane Pregnancy and Childbirth Group's Trials Register (31 October 2011) and
      reference lists of retrieved reports. SELECTION CRITERIA: We included randomised
      controlled trials and quasi-randomised controlled trials comparing topical
      preparations (with active ingredients) with other topical preparations (with
      active ingredients), with a placebo (that is, preparations without active
      ingredients) or with no treatment for the prevention of stretch marks in pregnant
      women. DATA COLLECTION AND ANALYSIS: Three review authors independently assessed
      trial eligibility and trial quality, and extracted data. Data were checked for
      accuracy. The primary outcome was the presence of stretch marks and the secondary
      outcome was the severity of stretch marks. MAIN RESULTS: We included six trials
      involving 800 women. Of the six trials, we judged the risk of bias for three as
      'low risk' for random sequence generation, blinding of participants and
      personnel, blinding of outcome assessment, completeness of outcome data and
      selective reporting.There was no statistically significant average difference in
      the development of stretch marks in women who received topical preparations with
      active ingredients compared to women who received a placebo or no treatment
      (average risk ratio (RR) 0.74; 95% confidence interval (CI) 0.53 to 1.03; five
      trials, 474 women; random-effects model, Tau2 = 0.09, I2 = 65%) (Analysis
      1.1).Results were consistent with the main effects when we performed a
      sensitivity analysis excluding studies judged to be at high risk of bias for
      random sequence generation, allocation concealment or more than 20% missing data
      for a given outcome (average RR 0.81; 95% CI 0.60 to 1.10; four trials, 424
      women; random-effects model, Tau2 = 0.05, I2 = 57%).The was no statistically
      significant average mean difference in the severity of stretch marks
      (standardised mean difference (SMD) -0.31; 95% CI -1.06 to 0.44; two trials, 255
      women; Tau2 = 0.26, I2 = 87%).There was no statistically significant difference
      in the development of stretch marks in women who received topical preparations
      with active ingredients compared to women who received other topical preparations
      with active ingredients (average RR 0.51; 95% CI 0.16 to 1.60; two trials, 305
      women; Tau2 = 0.53, I2 = 74%). There was no statistically significant difference
      in the severity of stretch marks (mean difference (MD) -0.20; 95% CI -0.53 to
      0.13; one trial, 206 women; heterogeneity not applicable). AUTHORS' CONCLUSIONS:
      We found no high-quality evidence to support the use of any of the topical
      preparations in the prevention of stretch marks during pregnancy. There is a
      clear need for robust, methodologically rigorous randomised trials involving
      larger sample sizes to evaluate the effects of topical preparations on the
      development of stretch marks in pregnancy. In addition, it is important that
      preparations commonly used by women to prevent and treat stretch marks are
      evaluated within the context of robust, methodologically rigorous and adequately
      powered randomised trials.

PMID- 23152200
TI  - Nicotine replacement therapy for smoking cessation.
AB  - BACKGROUND: The aim of nicotine replacement therapy (NRT) is to temporarily
      replace much of the nicotine from cigarettes to reduce motivation to smoke and
      nicotine withdrawal symptoms, thus easing the transition from cigarette smoking
      to complete abstinence. OBJECTIVES: The aims of this review were: To determine
      the effect of NRT compared to placebo in aiding smoking cessation, and to
      consider whether there is a difference in effect for the different forms of NRT
      (chewing gum, transdermal patches, oral and nasal sprays, inhalers and
      tablets/lozenges) in achieving abstinence from cigarettes. To determine whether
      the effect is influenced by the dosage, form and timing of use of NRT; the
      intensity of additional advice and support offered to the smoker; or the clinical
      setting in which the smoker is recruited and treated. To determine whether
      combinations of NRT are more likely to lead to successful quitting than one type
      alone. To determine whether NRT is more or less likely to lead to successful
      quitting compared to other pharmacotherapies. SEARCH METHODS: We searched the
      Cochrane Tobacco Addiction Group trials register for papers mentioning 'NRT' or
      any type of nicotine replacement therapy in the title, abstract or keywords. Date
      of most recent search July 2012. SELECTION CRITERIA: Randomized trials in which
      NRT was compared to placebo or to no treatment, or where different doses of NRT
      were compared. We excluded trials which did not report cessation rates, and those
      with follow-up of less than six months. DATA COLLECTION AND ANALYSIS: We
      extracted data in duplicate on the type of participants, the dose, duration and
      form of nicotine therapy, the outcome measures, method of randomization, and
      completeness of follow-up. The main outcome measure was abstinence from smoking
      after at least six months of follow-up. We used the most rigorous definition of
      abstinence for each trial, and biochemically validated rates if available. We
      calculated the risk ratio (RR) for each study. Where appropriate, we performed
      meta-analysis using a Mantel-Haenszel fixed-effect model. MAIN RESULTS: We
      identified 150 trials; 117 with over 50,000 participants contributed to the
      primary comparison between any type of NRT and a placebo or non-NRT control
      group. The risk ratio (RR) of abstinence for any form of NRT relative to control
      was 1.60 (95% confidence interval [CI] 1.53 to 1.68). The pooled RRs for each
      type were 1.49 (95% CI 1.40 to 1.60, 55 trials) for nicotine gum; 1.64 (95% CI
      1.52 to 1.78, 43 trials) for nicotine patch; 1.95 (95% CI 1.61 to 2.36, 6 trials)
      for oral tablets/lozenges; 1.90 (95% CI 1.36 to 2.67, 4 trials) for nicotine
      inhaler; and 2.02 (95% CI 1.49 to 2.73, 4 trials) for nicotine nasal spray. One
      trial of oral spray had an RR of 2.48 (95% CI 1.24 to 4.94). The effects were
      largely independent of the duration of therapy, the intensity of additional
      support provided or the setting in which the NRT was offered. The effect was
      similar in a small group of studies that aimed to assess use of NRT obtained
      without a prescription. In highly dependent smokers there was a significant
      benefit of 4 mg gum compared with 2 mg gum, but weaker evidence of a benefit from
      higher doses of patch. There was evidence that combining a nicotine patch with a
      rapid delivery form of NRT was more effective than a single type of NRT (RR 1.34,
      95% CI 1.18 to 1.51, 9 trials). The RR for NRT used for a short period prior to
      the quit date was 1.18 (95% CI 0.98 to 1.40, 8 trials), just missing statistical
      significance, though the efficacy increased when we pooled only patch trials and
      when we removed one trial in which confounding was likely. Five studies directly
      compared NRT to a non-nicotine pharmacotherapy, bupropion; there was no evidence
      of a difference in efficacy (RR 1.01; 95% CI 0.87 to 1.18). A combination of NRT
      and bupropion was more effective than bupropion alone (RR 1.24; 95% CI 1.06 to
      1.45, 4 trials). Adverse effects from using NRT are related to the type of
      product, and include skin irritation from patches and irritation to the inside of
      the mouth from gum and tablets. There is no evidence that NRT increases the risk
      of heart attacks. AUTHORS' CONCLUSIONS: All of the commercially available forms
      of NRT (gum, transdermal patch, nasal spray, inhaler and sublingual
      tablets/lozenges) can help people who make a quit attempt to increase their
      chances of successfully stopping smoking. NRTs increase the rate of quitting by
      50 to 70%, regardless of setting. The effectiveness of NRT appears to be largely
      independent of the intensity of additional support provided to the individual.
      Provision of more intense levels of support, although beneficial in facilitating
      the likelihood of quitting, is not essential to the success of NRT.

PMID- 23152201
TI  - Antioxidant vitamin and mineral supplements for slowing the progression of age
      related macular degeneration.
AB  - BACKGROUND: It has been proposed that antioxidants may prevent cellular damage in
      the retina by reacting with free radicals that are produced in the process of
      light absorption. Higher dietary levels of antioxidant vitamins and minerals may
      reduce the risk of progression of age-related macular degeneration (AMD).
      OBJECTIVES: The objective of this review was to assess the effects of antioxidant
      vitamin or mineral supplementation on the progression of AMD in people with AMD.
      SEARCH METHODS: We searched CENTRAL (which contains the Cochrane Eyes and Vision
      Group Trials Register) (The Cochrane Library 2012, Issue 8), Ovid MEDLINE, Ovid
      MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid
      OLDMEDLINE (January 1946 to August 2012), EMBASE (January 1980 to August 2012),
      Allied and Complementary Medicine Database (AMED) (January 1985 to August 2012),
      OpenGrey (System for Information on Grey Literature in Europe)
      (www.opengrey.eu/), 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 20 August 2012. We searched the reference lists of identified reports and the
      Science Citation Index. We contacted investigators and experts in the field for
      details of unpublished studies. We also searched for systematic reviews of harms
      of vitamin supplements. SELECTION CRITERIA: We included randomised trials
      comparing antioxidant vitamin or mineral supplementation (alone or in
      combination) to placebo or no intervention in people with AMD. DATA COLLECTION
      AND ANALYSIS: Two authors assessed risk of bias and extracted data from the
      included trials. Where appropriate, we pooled data using a random-effects model
      unless three or fewer trials were available in which case we used a fixed-effect
      model. MAIN RESULTS: Thirteen trials (6150 participants) were included in this
      review. Over half the participants (3640) were randomised in one trial (AREDS in
      the USA), which found a beneficial effect of antioxidant (beta-carotene, vitamin
      C and vitamin E) and zinc supplementation on progression to advanced AMD
      (adjusted odds ratio (OR) 0.68, 95% confidence interval (CI) 0.53 to 0.87) over
      an average of 6.3 years. People taking supplements were less likely to lose 15 or
      more letters of visual acuity (adjusted OR 0.77, 95% CI 0.62 to 0.96). The other
      trials, in general, had shorter follow-up (less than two years). No evidence for
      an effect of supplementation was seen in these smaller trials of shorter
      duration. Overall we considered the strength of the evidence to be moderate. We
      did not consider included trials, in general, to be at risk of bias, although we
      found it difficult to assess reporting biases. The main reason for downgrading
      the strength of the evidence was because, for several analyses, only one trial
      was included and therefore consistency of the findings could not be assessed. The
      included trials reported the following adverse effects: hospitalisation for
      genito-urinary problems was more common in people taking zinc and yellowing of
      skin was more common in people taking antioxidants. Systematic searching of the
      literature identified other potential harms of vitamin supplementation, in
      particular an increased risk of lung cancer in smokers associated with beta
      carotene supplements, but we were unable to identify a good systematic review of
      the evidence for harms of nutritional supplementation. AUTHORS' CONCLUSIONS:
      People with AMD may experience delay in progression of the disease with
      antioxidant vitamin and mineral supplementation. This finding is drawn from one
      large trial conducted in a relatively well-nourished American population. The
      generalisability of these findings to other populations is not known. Although
      generally regarded as safe, vitamin supplements may have harmful effects. A
      systematic review of the evidence on harms of vitamin supplements is needed.

PMID- 23152202
TI  - Compression for venous leg ulcers.
AB  - BACKGROUND: Up to one percent of people in industrialised countries will suffer
      from a leg ulcer at some time. The majority of these leg ulcers are due to
      problems in the veins, resulting in an accumulation of blood in the legs. Leg
      ulcers arising from venous problems are called venous (or varicose or stasis)
      ulcers. The main treatment is the application of a firm compression garment
      (bandage or stocking) in order to aid venous return. There is a large number of
      compression garments available and it was unclear whether they are effective in
      treating venous ulcers and, if so, which method of compression is the most
      effective. OBJECTIVES: To undertake a systematic review of all randomised
      controlled trials (RCTs) evaluating the effects on venous ulcer healing of
      compression bandages and stockings.Specific questions addressed by the review
      are:1. Does the application of compression bandages or stockings aid venous ulcer
      healing? 2. Which compression bandage or stocking system is the most effective?
      SEARCH METHODS: For this second update we searched: the Cochrane Wounds Group
      Specialised Register (31 May 2012); the Cochrane Central Register of Controlled
      Trials (CENTRAL) (The Cochrane Library Issue 5, 2012); Ovid MEDLINE (1950 to May
      Week 4 2012); Ovid MEDLINE (In-Process & Other Non-Indexed Citations 30 May
      2012); Ovid EMBASE (1980 to 2012 Week 21); and EBSCO CINAHL (1982 to 30 May
      2012). No date or language restrictions were applied. SELECTION CRITERIA: RCTs
      recruiting people with venous leg ulceration that evaluated any type of
      compression bandage system or compression stockings were eligible for inclusion.
      Eligible comparators included no compression (e.g. primary dressing alone, non
      compressive bandage) or an alternative type of compression. RCTs had to report an
      objective measure of ulcer healing in order to be included (primary outcome for
      the review). SECONDARY OUTCOMES of the review included ulcer recurrence, costs,
      quality of life, pain, adverse events and withdrawals. There was no restriction
      on date, language or publication status of RCTs. DATA COLLECTION AND ANALYSIS:
      Details of eligible studies were extracted and summarised using a data extraction
      table. Data extraction was performed by one review author and verified
      independently by a second review author. MAIN RESULTS: Forty-eight RCTs reporting
      59 comparisons were included (4321 participants in total). Most RCTs were small,
      and most were at unclear or high risk of bias. Duration of follow-up varied
      across RCTs. Risk ratio (RR) and other estimates are shown below where RCTs were
      pooled; otherwise findings refer to a single RCT.There was evidence from eight
      RCTs (unpooled) that healing outcomes (including time to healing) are better when
      patients receive compression compared with no compression.Single-component
      compression bandage systems are less effective than multi-component compression
      for complete healing at six months (one large RCT).A two-component system
      containing an elastic bandage healed more ulcers at one year than one without an
      elastic component (one small RCT).Three-component systems containing an elastic
      component healed more ulcers than those without elastic at three to four months
      (two RCTs pooled), RR 1.83 (95% CI 1.26 to 2.67), but another RCT showed no
      difference between groups at six months.An individual patient data meta-analysis
      of five RCTs suggested significantly faster healing with the four-layer bandage
      (4LB) than the short stretch bandage (SSB): median days to healing estimated at
      90 and 99 respectively; hazard ratio 1.31 (95% CI 1.09 to 1.58).High-compression
      stockings are associated with better healing outcomes than SSB at two to four
      months: RR 1.62 (95% CI 1.26 to 2.10), estimate from four pooled RCTs.One RCT
      suggested better healing outcomes at 16 months with the addition of a tubular
      device plus single elastic bandage to a base system of gauze and crepe bandages
      when compared with two added elastic bandages. Another RCT had three arms; when
      one or two elastic bandages were added to a base three-component system that
      included an outer tubular layer, healing outcomes were better at six months for
      the two groups receiving elastic bandages.There is currently no evidence of a
      statistically significant difference for the following comparisons:?alternative
      single-component compression bandages (two RCTs, unpooled);?two-component
      bandages compared with the 4LB at three months (three RCTs pooled);?alternative
      versions of the 4LB for complete healing at times up to and including six months
      (three RCTs, unpooled);?4LB compared with paste bandage for complete healing at
      three months (two RCTs, pooled), six months or one year (one RCT for each time
      point);?adjustable compression boots compared with paste bandages for the outcome
      of change in ulcer area at three months (one small RCT);?adjustable compression
      boots compared with the 4LB with respect to complete healing at three months (one
      small RCT);?single-layer compression stocking compared with paste bandages for
      outcome of complete healing at four months (one small RCT) and 18 months (another
      small RCT);?low compression stocking compared with SSB for complete healing at
      three and six months (one small RCT);?compression stockings compared with a two
      component bandage system and the 4LB for the outcome of complete healing at three
      months (one small, three-armed RCT); and,?tubular compression compared with SSB
      (one small RCT) for complete healing at three months. SECONDARY OUTCOMES: 4LB was
      more cost-effective than SSB. It was not possible to draw firm conclusions
      regarding other secondary outcomes including recurrence, adverse events and
      health-related quality of life. AUTHORS' CONCLUSIONS: Compression increases ulcer
      healing rates compared with no compression. Multi-component systems are more
      effective than single-component systems. Multi-component systems containing an
      elastic bandage appear to be more effective than those composed mainly of
      inelastic constituents. Two-component bandage systems appear to perform as well
      as the 4LB. Patients receiving the 4LB heal faster than those allocated the SSB.
      More patients heal on high-compression stocking systems than with the SSB.
      Further data are required before the difference between high-compression
      stockings and the 4LB can be established.

PMID- 23152203
TI  - Deworming drugs for soil-transmitted intestinal worms in children: effects on
      nutritional indicators, haemoglobin and school performance.
AB  - BACKGROUND: The World Health Organization (WHO) recommends treating all school
      children at regular intervals with deworming drugs in areas where helminth
      infection is common. The WHO state this will improve nutritional status,
      haemoglobin, and cognition and thus will improve health, intellect, and school
      attendance. Consequently, it is claimed that school performance will improve,
      child mortality will decline, and economic productivity will increase. Given the
      important health and societal benefits attributed to this intervention, we sought
      to determine whether they are based on reliable evidence. OBJECTIVES: To
      summarize the effects of giving deworming drugs to children to treat soil
      transmitted intestinal worms (nematode geohelminths) on weight, haemoglobin, and
      cognition; and the evidence of impact on physical well being, school attendance,
      school performance, and mortality. SEARCH METHODS: In February 2012, we searched
      the Cochrane Infectious Diseases Group Specialized Register, MEDLINE, EMBASE,
      LILACS, mRCT, and reference lists, and registers of ongoing and completed trials.
      SELECTION CRITERIA: We selected randomized controlled trials (RCTs) and quasi
      RCTs comparing deworming drugs for geohelminth worms with placebo or no treatment
      in children aged 16 years or less, reporting on weight, haemoglobin, and formal
      test of intellectual development. In cluster-RCTs treating communities or
      schools, we also sought data on school attendance, school performance, and
      mortality. We included trials that included health education with deworming. DATA
      COLLECTION AND ANALYSIS: At least two authors independently assessed the trials,
      evaluated risk of bias, and extracted data. Continuous data were analysed using
      the mean difference (MD) with 95% confidence intervals (CI). Where data were
      missing, we contacted trial authors. We used GRADE to assess evidence quality,
      and this is reflected in the wording we used: high quality ("deworming
      improves...."); moderate quality ("deworming probably improves..."); low quality
      ("deworming may improve...."); and very low quality ("we don't know if deworming
      improves...."). MAIN RESULTS: We identified 42 trials, including eight cluster
      trials, that met the inclusion criteria. Excluding one trial where data are
      awaited, the 41 trials include 65,168 participants.Screening then treatingFor
      children known to be infected with worms (by screening), a single dose of
      deworming drugs may increase weight (0.58 kg, 95% CI 0.40 to 0.76, three trials,
      139 participants; low quality evidence) and may increase haemoglobin (0.37 g/dL,
      95% CI 0.1 to 0.64, two trials, 108 participants; low quality evidence), but we
      do not know if there is an effect on cognitive functioning (two trials, very low
      quality evidence).Single dose deworming for all childrenIn trials treating all
      children, a single dose of deworming drugs gave mixed effects on weight, with no
      effects evident in seven trials, but large effects in two (nine trials, 3058
      participants, very low quality evidence). The two trials with a positive effect
      were from the same very high prevalence setting and may not be easily generalised
      elsewhere. Single dose deworming probably made little or no effect on haemoglobin
      (mean difference (MD) 0.06 g/dL, 95% CI -0.06 to 0.17, three trials, 1005
      participants; moderate evidence), and may have little or no effect on cognition
      (two trials, low quality evidence).Mulitple dose deworming for all childrenOver
      the first year of follow up, multiple doses of deworming drugs given to all
      children may have little or no effect on weight (MD 0.06 kg, 95% CI -0.17 to
      0.30; seven trials, 2460 participants; low quality evidence); haemoglobin, (mean
      0.01 g/dL lower; 95% CI 0.14 lower to 0.13 higher; four trials, 807 participants;
      low quality evidence); cognition (three trials, 30,571 participants, low quality
      evidence); or school attendance (4% higher attendance; 95% CI -6 to 14; two
      trials, 30,243 participants; low quality evidence);For time periods beyond a
      year, there were five trials with weight measures. One cluster-RCT of 3712
      children in a low prevalence area showed a large effect (average gain of 0.98
      kg), whilst the other four trials did not show an effect, including a cluster-RCT
      of 27,995 children in a moderate prevalence area (five trials, 37,306
      participants; low quality evidence). For height, we are uncertain whether there
      is an effect of deworming (-0.26 cm; 95% CI -0.84 to 0.31, three trials, 6652
      participants; very low quality evidence). Deworming may have little or no effect
      on haemoglobin (0.00 g/dL, 95%CI -0.08 to 0.08, two trials, 1365 participants,
      low quality evidence); cognition (two trials, 3720 participants; moderate quality
      evidence). For school attendance, we are uncertain if there is an effect (mean
      attendance 5% higher, 95% CI -0.5 to 10.5, approximately 20,000 participants,
      very low quality evidence).Stratified analysis to seek subgroup effects into low,
      medium and high helminth endemicity areas did not demonstrate any pattern of
      effect. In a sensitivity analysis that only included trials with adequate
      allocation concealment, we detected no significant effects for any primary
      outcomes.One million children were randomized in a deworming trial from India
      with mortality as the primary outcome. This was completed in 2005 but the authors
      have not published the results. AUTHORS' CONCLUSIONS: Screening children for
      intestinal helminths and then treating infected children appears promising, but
      the evidence base is small. Routine deworming drugs given to school children has
      been more extensively investigated, and has not shown benefit on weight in most
      studies, except for substantial weight changes in three trials conducted 15 years
      ago or more. Two of these trials were carried out in the same high prevalence
      setting. For haemoglobin and cognition, community deworming seems to have little
      or no effect, and the evidence in relation to school attendance, and school
      performance is generally poor, with no obvious or consistent effect. Our
      interpretation of this data is that it is probably misleading to justify
      contemporary deworming programmes based on evidence of consistent benefit on
      nutrition, haemoglobin, school attendance or school performance as there is
      simply insufficient reliable information to know whether this is so.

PMID- 23152204
TI  - Continuous and interrupted suturing techniques for repair of episiotomy or second
      degree tears.
AB  - BACKGROUND: Millions of women worldwide undergo perineal suturing after
      childbirth and the type of repair may have an impact on pain and healing. For
      more than 70 years, researchers have been suggesting that continuous non-locking
      suture techniques for repair of the vagina, perineal muscles and skin are
      associated with less perineal pain than traditional interrupted methods.
      OBJECTIVES: To assess the effects of continuous versus interrupted absorbable
      sutures for repair of episiotomy and second-degree perineal tears following
      childbirth. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth
      Group's Trials Register (20 January 2012). SELECTION CRITERIA: Randomised trials
      examining continuous and interrupted suturing techniques for repair of episiotomy
      and second-degree tears after vaginal delivery. DATA COLLECTION AND ANALYSIS:
      Three review authors independently assessed trial quality. Two of the three
      authors independently extracted data and a third review author checked them. We
      contacted study authors for additional information. MAIN RESULTS: Sixteen
      studies, involving 8184 women at point of entry, from eight countries, were
      included. The trials were heterogeneous in respect of operator skill and
      training. Meta-analysis showed that continuous suture techniques compared with
      interrupted sutures for perineal closure (all layers or perineal skin only) are
      associated with less pain for up to 10 days' postpartum (risk ratio (RR) 0.76;
      95% confidence interval (CI) 0.66 to 0.88, nine trials). There was an overall
      reduction in analgesia use associated with the continuous subcutaneous technique
      versus interrupted stitches for repair of perineal skin (RR 0.70; 95% CI 0.59 to
      0.84). There was also a reduction in suture removal in the continuous suturing
      groups versus interrupted (RR 0.56; 95% CI 0.32 to 0.98), but no significant
      differences were seen in the need for re-suturing of wounds or long-term pain.
      AUTHORS' CONCLUSIONS: The continuous suturing techniques for perineal closure,
      compared with interrupted methods, are associated with less short-term pain, need
      for analgesia and suture removal. Furthermore, there is also some evidence that
      the continuous techniques used less suture material as compared with the
      interrupted methods (one packet compared to two or three packets, respectively).

PMID- 23152205
TI  - Antimicrobials for treating symptomatic non-typhoidal Salmonella infection.
AB  - BACKGROUND: Non-typhoidal Salmonella (NTS) commonly causes diarrhoea, and is
      usually self-limiting, although sometimes people become ill with sepsis and
      dehydration. Routine antibiotic use for this infection could result in persistent
      colonization and the spread of resistant bacterial strains. OBJECTIVES: To assess
      the efficacy and safety of giving antibiotics to people with NTS diarrhoea.
      SEARCH METHODS: We searched the Cochrane Infectious Diseases Group trials
      register (up to August 2012), the Cochrane Controlled Trials Register (CENTRAL)
      published in The Cochrane Library (up to Issue 8 2012); and MEDLINE, African
      Index Medicus, CINAHL, EMBASE, LILACS, and the Science Citation Index, all up to
      6 August 2012. We also searched the metaRegister of Controlled Trials (mRCT) for
      both completed and on going trials and reference lists of relevant articles.
      SELECTION CRITERIA: Randomized controlled trials (RCTs) comparing any antibiotic
      treatment for diarrhoea caused by NTS species with placebo or no antibiotic
      treatment. We selected trials that included people of all ages who were
      symptomatic for NTS infection. Examples of symptoms included fever, abdominal
      pain, vomiting and diarrhoea. We excluded trials where the outcomes were not
      reported separately for the NTS subgroup of patients. Two review authors
      independently applied eligibility criteria prior to study inclusion. DATA
      COLLECTION AND ANALYSIS: Two review authors independently extracted data on pre
      specified outcomes and independently assessed the risk of bias of included
      studies. The primary outcome was the presence of diarrhoea between two to four
      days after treatment. The quality of evidence was assessed using the GRADE
      methods. MAIN RESULTS: Twelve trials involving 767 participants were included. No
      differences were detected between the antibiotic and placebo/no treatment arms
      for people with diarrhoea at two to four days after treatment (risk ratio (RR)
      1.75, 95% confidence interval (CI) 0.42 to 7.21; one trial, 46 participants; very
      low quality evidence). No difference was detected for the presence of diarrhoea
      at five to seven days after treatment (RR 0.83, 95% CI 0.62 to 1.12; two trials,
      192 participants; very low quality evidence), clinical failure (RR 0.88, 95% CI
      0.62 to 1.25; seven trials, 440 participants; very low quality evidence). The
      mean difference for diarrhoea was 0 days (95% CI -0.54 to 0.54; 202 participants,
      four studies; low quality evidence);for fever was 0.27 days (95% CI -0.11 to
      0.65; 107 participants, two studies; very low quality evidence); and for duration
      of illness was 0 days (95% CI -0.68 to 0.68; 116 participants, two studies; very
      low quality evidence). Quinolone antibiotic treatment resulted in a significantly
      higher number of negative stool cultures for NTS during the first week of
      treatment (microbiological failure: RR 0.33, 95% CI 0.20 to 0.56; 166
      participants, four trials).Antibiotic treatment meant passage of the same
      Salmonella serovar one month after treatment was almost twice as likely (RR 1.96,
      95% CI 1.29 to 2.98; 112 participants, three trials), which was statistically
      significant. Non-severe adverse drug reactions were more common among the
      patients who received antibiotic treatment. AUTHORS' CONCLUSIONS: There is no
      evidence of benefit for antibiotics in NTS diarrhoea in otherwise healthy people.
      We are uncertain of the effects in very young people, very old people, and in
      people with severe and extraintestinal disease. A slightly higher number of
      adverse events were noted in people who received antibiotic treatment for NTS.

PMID- 23152206
TI  - Topical agents or dressings for pain in venous leg ulcers.
AB  - BACKGROUND: Venous leg ulcers affect up to 1% of people at some time in their
      lives and are often painful. The main treatments are compression bandages and
      dressings. Topical treatments to reduce pain during and between dressing changes
      are sometimes used. OBJECTIVES: To determine the effects of topical agents or
      dressings for pain in venous leg ulcers. SEARCH METHODS: For this third update
      the following databases were searched: Cochrane Wounds Group Specialised Register
      (searched 9 May 2012); The Cochrane Central Register of Controlled Trials
      (CENTRAL) (The Cochrane Library 2012, Issue 4); Ovid MEDLINE (2009 to April Week
      4 2012); Ovid MEDLINE (In-Process & Other Non-Indexed Citations May 08, 2012);
      Ovid EMBASE (2009 to 2012 Week 18); and EBSCO CINAHL (2009 to May 2 2012). No
      date or language restrictions were applied. SELECTION CRITERIA: Published or
      unpublished randomised controlled trials (RCTs) that evaluated the effects of
      topical agents or dressing for the treatment of pain in venous ulcers were
      included. DATA COLLECTION AND ANALYSIS: Two review authors independently
      performed trial selection, data extraction and risk of bias assessment. MAIN
      RESULTS: Six trials (343 participants) evaluated Eutectic Mixture of Local
      Anaesthetics (EMLA): lidocaine-prilocaine cream for the pain associated with
      ulcer debridement. The between-group difference in pain measured on a 100 mm
      scale was statistically significant in favour of EMLA (MD -20.65, 95% CI -12.19
      to -29.11). No significant between-group differences in burning or itching were
      observed.Two trials (470 participants with venous leg ulcers) evaluated ibuprofen
      slow-release foam dressings for persistent venous leg ulcer pain. Compared with
      local best practice, significantly more participants in the ibuprofen dressing
      group achieved the outcome of >50% of the total maximum pain relief score between
      day 1 and day 5 than participants in the local best practice group (RR 1.63, 95%
      CI 1.24 to 2.15). The number needed to treat was 6 (95% CI 4 to 12). In the
      second trial, compared with an identical non-ibuprofen foam dressing, there was
      no statistically significant difference in the proportion of participants
      experiencing slight to complete pain relief on the first evening of
      treatment.Limited data were available to assess healing rates or adverse events.
      AUTHORS' CONCLUSIONS: There is some evidence to suggest that ibuprofen dressings
      may offer pain relief to people with painful venous leg ulcers. EMLA (5%) appears
      to provide effective pain relief during the debridement of venous leg ulcers.
      Further research should consider standardised pain assessment methods and assess
      both the effect on ulcer healing and the impact of long term use of these
      treatments.

PMID- 23152207
TI  - Early versus delayed selective surfactant treatment for neonatal respiratory
      distress syndrome.
AB  - BACKGROUND: Clinical trials have confirmed that surfactant therapy is effective
      in improving the immediate need for respiratory support and the clinical outcome
      of premature newborns. Trials have studied a wide variety of surfactant
      preparations used either to prevent (prophylactic or delivery room
      administration) or treat (selective or rescue administration) respiratory
      distress syndrome (RDS). Using either treatment strategy, significant reductions
      in the incidence of pneumothorax, as well as significant improvement in survival,
      have been noted. It is unclear whether there are any advantages to treating
      infants with respiratory insufficiency earlier in the course of RDS. OBJECTIVES:
      To compare the effects of early versus delayed selective surfactant therapy for
      newborns intubated for respiratory distress within the first two hours of life.
      Planned subgroup analyses included separate comparisons for studies utilizing
      natural surfactant extract and synthetic surfactant. SEARCH METHODS: We searched
      the Oxford Database of Perinatal Trials, MEDLINE (MeSH terms: pulmonary
      surfactant; text word: early; limits: age, newborn: publication type, clinical
      trial), PubMed, abstracts, conference and symposia proceedings, expert
      informants, and journal handsearching in the English language. For the updated
      search in April 2012 we searched the Cochrane Central Register of Controlled
      Trials (CENTRAL, The Cochrane Library, 2012, Issue 1) and PubMed (January 1997 to
      April 2012). SELECTION CRITERIA: Randomized and quasi-randomized controlled
      clinical trials comparing early selective surfactant administration (surfactant
      administration via the endotracheal tube in infants intubated for respiratory
      distress, not specifically for surfactant dosage) within the first two hours of
      life versus delayed selective surfactant administration to infants with
      established RDS were considered for review. DATA COLLECTION AND ANALYSIS: Data
      regarding clinical outcomes were excerpted from the reports of the clinical
      trials by the review authors. Subgroup analyses were performed based on type of
      surfactant preparation, gestational age, and exposure to prenatal steroids. Data
      analysis was performed in accordance with the standards of the Cochrane Neonatal
      Review Group. MAIN RESULTS: Six randomized controlled trials met selection
      criteria. Two of the trials utilized synthetic surfactant (Exosurf Neonatal) and
      four utilized animal-derived surfactant preparations.The meta-analyses
      demonstrate significant reductions in the risk of neonatal mortality (typical
      risk ratio (RR) 0.84; 95% confidence interval (CI) 0.74 to 0.95; typical risk
      difference (RD) -0.04; 95% CI -0.06 to -0.01; 6 studies; 3577 infants), chronic
      lung disease (typical RR 0.69; 95% CI 0.55 to 0.86; typical RD -0.04; 95% CI 
      0.06 to -0.01; 3 studies; 3041 infants), and chronic lung disease or death at 36
      weeks (typical RR 0.83; 95% CI 0.75 to 0.91; typical RD -0.06; 95% CI -0.09 to 
      0.03; 3 studies; 3050 infants) associated with early treatment of intubated
      infants with RDS.Intubated infants randomized to early selective surfactant
      administration also demonstrated a decreased risk of acute lung injury including
      a decreased risk of pneumothorax (typical RR 0.69; 95% CI 0.59 to 0.82; typical
      RD -0.05; 95% CI -0.08 to -0.03; 5 studies; 3545 infants), pulmonary interstitial
      emphysema (typical RR 0.60; 95% CI 0.41 to 0.89; typical RD -0.06; 95% CI -0.10
      to -0.02; 3 studies; 780 infants), and overall air leak syndromes (typical RR
      0.61; 95% CI 0.48 to 0.78; typical RD -0.18; 95% CI -0.26 to -0.09; 2 studies;
      463 infants).A trend toward risk reduction for bronchopulmonary dysplasia (BPD)
      or death at 28 days was also evident (typical RR 0.94; 95% CI 0.88 to 1.00;
      typical RD -0.04; 95% CI -0.07 to -0.00; 3 studies; 3039 infants). No differences
      in other complications of RDS or prematurity were noted.Only two studies reported
      on infants under 30 weeks' gestation. Decreased risk of neonatal mortality and
      chronic lung disease or death at 36 weeks' postmenstrual age was noted. AUTHORS'
      CONCLUSIONS: Early selective surfactant administration given to infants with RDS
      requiring assisted ventilation leads to a decreased risk of acute pulmonary
      injury (decreased risk of pneumothorax and pulmonary interstitial emphysema) and
      a decreased risk of neonatal mortality and chronic lung disease compared to
      delaying treatment of such infants until they develop worsening RDS.

PMID- 23152208
TI  - Bromperidol decanoate (depot) for schizophrenia.
AB  - BACKGROUND: Antipsychotic drugs are the mainstay treatment for schizophrenia.
      Long-acting depot injections of drugs such as bromperidol decanoate are
      extensively used as a means of long-term maintenance treatment. OBJECTIVES: To
      assess the effects of depot bromperidol versus placebo, oral antipsychotics and
      other depot antipsychotic preparations for people with schizophrenia in terms of
      clinical, social and economic outcomes. SEARCH METHODS: For this 2012 update we
      searched the Cochrane Schizophrenia Group's Register (February 2012). SELECTION
      CRITERIA: We sought all randomised trials focusing on people with schizophrenia
      where depot bromperidol, oral antipsychotics or other depot preparations. Primary
      outcomes were clinically significant change in global function, service
      utilisation outcomes (hospital admission, days in hospital), relapse. DATA
      COLLECTION AND ANALYSIS: For the 2011 update MP independently extracted data, CEA
      carried out the reliability check. We calculated fixed-effect risk ratios (RR)
      and 95% confidence intervals (CI) for dichotomous data, and calculated weighted
      or standardised means for continuous data. Where possible, we calculated the
      number needed to treat statistic (NNT). Analysis was by intention-to-treat.For
      the 2012 update, data collection and analysis was not carried out as no new
      studies were found. MAIN RESULTS: The 2012 search found no new studies, we have
      therefore included no new trials in this 2012 update. The number of included
      trials remain 4 RCTs, total n = 117. A single, small study of six months'
      duration compared bromperidol decanoate with placebo injection. Similar numbers
      left the study before completion (n = 20, 1 RCT, RR 0.4 CI 0.1 to 1.6) and there
      were no clear differences between bromperidol decanoate and placebo for a list of
      adverse effects (n = 20, 1 RCT, RR akathisia 2.0 CI 0.21 to 18.69, RR increased
      weight 3.0 CI 0.14 to 65.9, RR tremor 0.33 CI 0.04 to 2.69). When bromperidol
      decanoate was compared with fluphenazine depot, we found no important change on
      global outcome (n = 30, RR no clinical important improvement 1.50 CI 0.29 to
      7.73). People allocated to fluphenazine decanoate and haloperidol decanoate had
      fewer relapses than those given bromperidol decanoate (n = 77, RR 3.92 Cl 1.05 to
      14.60, NNH 6 CI 2 to 341). People allocated bromperidol decanoate required
      additional antipsychotic medication somewhat more frequently than those taking
      fluphenazine decanoate and haloperidol decanoate, but the results did not reach
      conventional levels of statistical significance (n = 77, 2 RCTs, RR 1.72 CI 0.7
      to 4.2). The use of benzodiazepine drugs was very similar in both groups (n = 77,
      2 RCTs, RR 1.08 CI 0.68 to 1.70). People left the bromperidol decanoate group
      more frequent than those taking other depot preparation due to any cause (n = 97,
      3 RCTs, RR 2.17 CI 1.00 to 4.73). Anticholinergic adverse effects were equally
      common between bromperidol and other depots (n = 47, RR 3.13 CI 0.7 to 14.0) and
      additional anticholinergic medication was needed with equal frequency in both
      depot groups, although results did tend to favour the bromperidol decanoate group
      (n = 97, 3 RCTs, RR 0.80 CI 0.64 to 1.01). The incidence of movement disorders
      was similar in both depot groups (n = 77, 2 RCTs, RR 0.74 CI 0.47 to 1.17).
      AUTHORS' CONCLUSIONS: Minimal poorly reported trial data suggests that
      bromperidol decanoate may be better than placebo injection but less valuable than
      fluphenazine or haloperidol decanoate. If bromperidol decanoate is available it
      may be a viable choice, especially when there are reasons not to use fluphenazine
      or haloperidol decanoate. Well-conducted and reported randomised trials are
      needed to inform practice.

PMID- 23152209
TI  - Inhaled corticosteroids for cystic fibrosis.
AB  - BACKGROUND: Reduction of lung inflammation is one of the goals of cystic fibrosis
      (CF) therapy. Inhaled corticosteroids (ICS) are often used to treat children and
      adults with CF. The rationale for this is their potential to reduce lung damage
      arising from inflammation, as well as their effect on symptomatic wheezing. It is
      important to establish the current level of evidence for the risks and benefits
      of ICS, especially in the light of their known adverse effects on growth.
      OBJECTIVES: To assess the effectiveness of taking regular ICS, compared to not
      taking them, in children and adults with CF. SEARCH METHODS: We searched the
      Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register, comprising
      references identified from comprehensive electronic database searches and
      handsearches of relevant journals and abstract books of conference proceedings.
      We requested information from pharmaceutical companies manufacturing inhaled
      corticosteroids and authors of identified trials.Date of most recent search of
      the Group's Trials Register: 03 September 2012. SELECTION CRITERIA: Randomised or
      quasi-randomised trials, published and unpublished, comparing ICS to placebo or
      standard treatment in individuals with CF. DATA COLLECTION AND ANALYSIS: Two
      independent authors assessed methodological quality of trials using established
      criteria and extracted data using standard pro formas. MAIN RESULTS: The searches
      identified 34 citations, of which 26 (representing 13 trials) were eligible for
      inclusion. These 13 trials reported the use of ICS in 506 people with CF aged
      between 6 and 55 years. One trial was a withdrawal study in individuals who were
      already taking ICS. Methodological quality was difficult to assess from published
      information. Inclusion criteria varied between trials, as did type and duration
      of treatment and timing of outcome assessments. Objective measures of airway
      function were reported in most trials but were often incomplete. Significant
      benefit has not been conclusively demonstrated. Four trials systematically
      documented adverse effects and growth was significantly affected in one study
      using high doses. AUTHORS' CONCLUSIONS: Evidence from these trials is
      insufficient to establish whether ICS are beneficial in CF, but withdrawal in
      those already taking them has been shown to be safe. There is some evidence they
      may cause harm in terms of growth. It has not been established whether long-term
      use is beneficial in reducing lung inflammation, which should improve survival,
      but it is unlikely this will be proven conclusively in a randomised controlled
      trial.

PMID- 23152210
TI  - Information provision for stroke patients and their caregivers.
AB  - BACKGROUND: Research shows that stroke patients and their families are
      dissatisfied with the information provided and have a poor understanding of
      stroke and associated issues. OBJECTIVES: To assess the effectiveness of
      information provision strategies in improving the outcome for stroke patients or
      their identified caregivers, or both. SEARCH METHODS: For this update we searched
      the Cochrane Stroke Group Trials Register (June 2012), the Cochrane Central
      Register of Controlled trials (CENTRAL), the Cochrane Database of Systematic
      Reviews (CDSR), the Database of Abstracts of Reviews of Effects (DARE), the NHS
      Economic Evaluation Database (EED), and the Health Technology Assessment (HTA)
      Database (The Cochrane Library June, 2012), MEDLINE (1966 to June 2012), EMBASE
      (1980 to June 2012), CINAHL (1982 to June 2012) and PsycINFO (1974 to June 2012).
      We also searched ongoing trials registers, scanned bibliographies of relevant
      articles and books and contacted researchers. SELECTION CRITERIA: Randomised
      trials involving patients or carers of patients with a clinical diagnosis of
      stroke or transient ischaemic attack (TIA) where an information intervention was
      compared with standard care, or where information and another therapy were
      compared with the other therapy alone. DATA COLLECTION AND ANALYSIS: Two review
      authors independently assessed trial eligibility and methodological quality and
      extracted data. Primary outcomes were knowledge about stroke and stroke services,
      and impact on mood. MAIN RESULTS: We have added four new trials to this update.
      This review now includes 21 trials involving 2289 patient and 1290 carer
      participants. Nine trials evaluated a passive and 12 trials an active information
      intervention. Meta-analyses showed a significant effect in favour of the
      intervention on patient knowledge (standardised mean difference (SMD) 0.29, 95%
      confidence interval (CI) 0.12 to 0.46, P < 0.001), carer knowledge (SMD 0.74, 95%
      CI 0.06 to 1.43, P = 0.03), one aspect of patient satisfaction (odds ratio (OR)
      2.07, 95% CI 1.33 to 3.23, P = 0.001), and patient depression scores (mean
      difference (MD) -0.52, 95% CI -0.93 to -0.10, P = 0.01). There was no significant
      effect (P > 0.05) on number of cases of anxiety or depression in patients, carer
      mood or satisfaction, or death. Qualitative analyses found no strong evidence of
      an effect on other outcomes. Post-hoc subgroup analyses showed that active
      information had a significantly greater effect than passive information on
      patient mood but not on other outcomes. AUTHORS' CONCLUSIONS: There is evidence
      that information improves patient and carer knowledge of stroke, aspects of
      patient satisfaction, and reduces patient depression scores. However, the
      reduction in depression scores was small and may not be clinically significant.
      Although the best way to provide information is still unclear there is some
      evidence that strategies that actively involve patients and carers and include
      planned follow-up for clarification and reinforcement have a greater effect on
      patient mood.

PMID- 23152211
TI  - Beta-blockers for hypertension.
AB  - BACKGROUND: This review is an update of the Cochrane Review published in 2007,
      which assessed the role of beta-blockade as first-line therapy for hypertension.
      OBJECTIVES: To quantify the effectiveness and safety of beta-blockers on
      morbidity and mortality endpoints in adults with hypertension. SEARCH METHODS: In
      December 2011 we searched the Cochrane Central Register of Controlled Trials,
      Medline, Embase, and reference lists of previous reviews; for eligible studies
      published since the previous search we conducted in May 2006. SELECTION CRITERIA:
      Randomised controlled trials (RCTs) of at least one year duration, which assessed
      the effects of beta-blockers compared to placebo or other drugs, as first-line
      therapy for hypertension, on mortality and morbidity in adults. DATA COLLECTION
      AND ANALYSIS: We selected studies and extracted data in duplicate. We expressed
      study results as risk ratios (RR) with 95% confidence intervals (CI) and combined
      them using the fixed-effects or random-effects method, as appropriate. MAIN
      RESULTS: We included 13 RCTs which compared beta-blockers to placebo (4 trials,
      N=23,613), diuretics (5 trials, N=18,241), calcium-channel blockers (CCBs: 4
      trials, N=44,825), and renin-angiotensin system (RAS) inhibitors (3 trials,
      N=10,828). Three-quarters of the 40,245 participants on beta-blockers used
      atenolol. Most studies had a high risk of bias; resulting from various
      limitations in study design, conduct, and data analysis.Total mortality was not
      significantly different between beta-blockers and placebo (RR 0.99, 95%CI 0.88 to
      1.11; I(2)=0%), diuretics or RAS inhibitors, but was higher for beta-blockers
      compared to CCBs (RR 1.07, 95%CI 1.00 to 1.14; I(2)=2%). Total cardiovascular
      disease (CVD) was lower for beta-blockers compared to placebo (RR 0.88, 95%CI
      0.79 to 0.97; I(2)=21%). This is primarily a reflection of the significant
      decrease in stroke (RR 0.80, 95%CI 0.66 to 0.96; I(2)=0%), since there was no
      significant difference in coronary heart disease (CHD) between beta-blockers and
      placebo. There was no significant difference in withdrawals from assigned
      treatment due to adverse events between beta-blockers and placebo (RR 1.12, 95%CI
      0.82 to 1.54; I(2)=66%).The effect of beta-blockers on CVD was significantly
      worse than that of CCBs (RR 1.18, 95%CI 1.08-1.29; I(2)=0%), but was not
      different from that of diuretics or RAS inhibitors. In addition, there was an
      increase in stroke in beta-blockers compared to CCBs (RR 1.24, 95%CI 1.11-1.40;
      I(2)=0%) and RAS inhibitors (RR 1.30, 95%CI 1.11 to 1.53; I(2)=29%). However, CHD
      was not significantly different between beta-blockers and diuretics, CCBs or RAS
      inhibitors. Participants on beta-blockers were more likely to discontinue
      treatment due to adverse events than those on RAS inhibitors (RR 1.41, 95% CI
      1.29 to 1.54; I(2)=12%), but there was no significant difference with diuretics
      or CCBs. AUTHORS' CONCLUSIONS: Initiating treatment of hypertension with beta
      blockers leads to modest reductions in cardiovascular disease and no significant
      effects on mortality. These effects of beta-blockers are inferior to those of
      other antihypertensive drugs. The GRADE quality of this evidence is low, implying
      that the true effect of beta-blockers may be substantially different from the
      estimate of effects found in this review. Further research should be of high
      quality and should explore whether there are differences between different sub
      types of beta-blockers or whether beta-blockers have differential effects on
      younger and elderly patients.

PMID- 23152212
TI  - Recombinant human insulin-like growth factor I (rhIGF-I) for the treatment of
      amyotrophic lateral sclerosis/motor neuron disease.
AB  - BACKGROUND: Recombinant human insulin-like growth factor I (rhIGF-I) is a
      possible disease modifying therapy for amyotrophic lateral sclerosis (ALS, which
      is also known as motor neuron disease (MND)). OBJECTIVES: To examine the efficacy
      of rhIGF-I in affecting disease progression, impact on measures of functional
      health status, prolonging survival and delaying the use of surrogates
      (tracheostomy and mechanical ventilation) to sustain survival in ALS. Occurrence
      of adverse events was also reviewed. SEARCH METHODS: We searched the Cochrane
      Neuromuscular Disease Group Specialized Register (21 November 2011), CENTRAL
      (2011, Issue 4), MEDLINE (January 1966 to November 2011) and EMBASE (January 1980
      to November 2011) and sought information from the authors of randomised clinical
      trials and manufacturers of rhIGF-I. SELECTION CRITERIA: We considered all
      randomised controlled clinical trials involving rhIGF-I treatment of adults with
      definite or probable ALS according to the El Escorial Criteria. The primary
      outcome measure was change in Appel Amyotrophic Lateral Sclerosis Rating Scale
      (AALSRS) total score after nine months of treatment and secondary outcome
      measures were change in AALSRS at 1, 2, 3, 4, 5, 6, 7, 8, 9 months, change in
      quality of life (Sickness Impact Profile scale), survival and adverse events.
      DATA COLLECTION AND ANALYSIS: Each author independently graded the risk of bias
      in the included studies. The lead author extracted data and the other authors
      checked them. We generated some missing data by making ruler measurements of data
      in published graphs. We collected data about adverse events from the included
      trials. MAIN RESULTS: We identified three randomised controlled trials (RCTs) of
      rhIGF-I, involving 779 participants, for inclusion in the analysis. In a European
      trial (183 participants) the mean difference (MD) in change in AALSRS total score
      after nine months was -3.30 (95% confidence interval (CI) -8.68 to 2.08). In a
      North American trial (266 participants), the MD after nine months was -6.00 (95%
      CI -10.99 to -1.01). The combined analysis from both RCTs showed a MD after nine
      months of -4.75 (95% CI -8.41 to -1.09), a significant difference in favour of
      the treated group. The secondary outcome measures showed non-significant trends
      favouring rhIGF-I. There was an increased risk of injection site reactions with
      rhIGF-I (risk ratio 1.26, 95% CI 1.04 to 1.54). . A second North American trial
      (330 participants) used a novel primary end point involving manual muscle
      strength testing. No differences were demonstrated between the treated and
      placebo groups in this study. All three trials were at high risk of bias.
      AUTHORS' CONCLUSIONS: Meta-analysis revealed a significant difference in favour
      of rhIGF-I treatment; however, the quality of the evidence from the two included
      trials was low. A third study showed no difference between treatment and placebo.
      There is no evidence for increase in survival with IGF1. All three included
      trials were at high risk of bias.

PMID- 23152213
TI  - Primary care professionals providing non-urgent care in hospital emergency
      departments.
AB  - BACKGROUND: In many countries emergency departments (EDs) are facing an increase
      in demand for services, long-waits and severe crowding. One response to mitigate
      overcrowding has been to provide primary care services alongside or within
      hospital EDs for patients with non-urgent problems. It is not known, however, how
      this impacts the quality of patient care, the utilisation of hospital resources,
      or if it is cost-effective.  OBJECTIVES: To assess the effects of locating
      primary care professionals in the hospital ED to provide care for patients with
      non-urgent health problems, compared with care provided by regular Emergency
      Physicians (EPs), SEARCH METHODS: We searched the Cochrane Effective Practice and
      Organisation of Care (EPOC) Group Specialized register; Cochrane Central Register
      of Controlled Trials (The Cochrane library, 2011, Issue 4), MEDLINE (1950 to
      March 21 2012); EMBASE (1980 to April 28 2011); CINAHL (1980 to April 28 2011);
      PsychINFO (1967 to April 28 2011); Sociological Abstracts (1952 to April 28
      2011); ASSIA (1987 to April 28 2011); SSSCI (1945 to April 28 2011); HMIC (1979
      to April 28 2011), sources of unpublished literature, reference lists of included
      papers and relevant systematic reviews. We contacted experts in the field for any
      published or unpublished studies, and hand searched ED conference abstracts from
      the last three years. SELECTION CRITERIA: Randomised controlled trials, non
      randomised studies, controlled before and after studies and interrupted time
      series studies that evaluated the effectiveness of introducing primary care
      professionals to hospital EDs to attend to non-urgent patients, as compared to
      the care provided by regular EPs.  DATA COLLECTION AND ANALYSIS: Two reviewers
      independently extracted data and assessed the risk of bias for each included
      study. We contacted authors of included studies to obtain additional data.
      Dichotomous outcomes are presented as risk ratios (RR) with 95% confidence
      intervals (CIs) and continuous outcomes are presented as mean differences (MD)
      with 95% CIs. Pooling was not possible due to heterogeneity. MAIN RESULTS: Three
      non randomised controlled studies involving a total of 11 203 patients, 16
      General Practioners (GPs), and 52 EPs, were included. These studies evaluated the
      effects of introducing GPs to provide care to patients with non-urgent problems
      in the ED, as compared to EPs for outcomes such as resource use. The quality of
      evidence for all outcomes in this review was low, primarily due to the non
      randomised design of included studies.The outcomes investigated were similar
      across studies; however there was high heterogeneity (I(2)>86%). Differences
      across studies included the triage system used, the level of expertise and
      experience of the medical practitioners and type of hospital (urban teaching,
      suburban community hospital).Two of the included studies report that GPs used
      significantly fewer healthcare resources than EPs, with fewer blood tests (RR
      0.22; 95%CI: 0.14 to 0.33; N=4641; RR 0.35; 95%CI 0.29 to 0.42; N=4684), x-rays
      (RR 0.47; 95% CI 0.41 to 0.54; N=4641; RR 0.77 95% CI 0.72 to 0.83; N=4684),
      admissions to hospital (RR 0.33; 95% CI 0.19 to 0.58; N=4641; RR 0.45; 95% CI
      0.36 to 0.56; N=4684) and referrals to specialists (RR 0.50; 95% CI 0.39 to 0.63;
      N=4641; RR 0.66; 95% CI 0.60 to 0.73; N=4684). One of the two studies reported no
      statistically significant difference in the number of prescriptions made by GPs
      compared with EPs, (RR 0.95 95% CI 0.88 to 1.03; N=4641), while the other showed
      that GPs prescribed significantly more medications than EPs (RR 1.45 95% CI 1.35
      to 1.56; N=4684). The results from these two studies showed marginal cost savings
      from introducing GPs in hospital EDs.The third study (N=1878) failed to identify
      a significant difference in the number of blood tests ordered (RR 0.96; 95% CI
      0.76 to 1.2), x-rays (RR 1.07; 95%CI 0.99 to 1.15), or admissions to hospital (RR
      1.11; 95% CI 0.70 to 1.76), but reported a significantly greater number of
      referrals to specialists (RR 1.21; 95% CI 1.09 to 1.33) and prescriptions (RR
      1.12; 95% CI 1.01 to 1.23) made by GPs as compared with EPs.No data were reported
      on patient wait-times, length of hospital stay, or patient outcomes, including
      adverse effects or mortality. AUTHORS' CONCLUSIONS: Overall, the evidence from
      the three included studies is weak, as results are disparate and neither safety
      nor patient outcomes have been examined. There is insufficient evidence upon
      which to draw conclusions for practice or policy regarding the effectiveness and
      safety of care provided to non-urgent patients by GPs versus EPs in the ED to
      mitigate problems of overcrowding, wait-times and patient flow.

PMID- 23152214
TI  - Macrolide antibiotics for cystic fibrosis.
AB  - BACKGROUND: Macrolide antibiotics may have a modifying role in diseases which
      involve airway infection and inflammation, like cystic fibrosis. OBJECTIVES: To
      test the hypotheses that, in people with cystic fibrosis, macrolide antibiotics:
      1. improve clinical status compared to placebo or another antibiotic; 2. do not
      have unacceptable adverse effects. If benefit was demonstrated, we aimed to
      assess the optimal type, dose and duration of macrolide therapy. SEARCH METHODS:
      We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials
      Register comprising references identified from comprehensive electronic database
      searches, handsearching relevant journals and abstract books of conference
      proceedings.We contacted investigators known to work in the field, previous
      authors and pharmaceutical companies manufacturing macrolide antibiotics for
      unpublished or follow-up data (May 2010).Latest search of the Group's Cystic
      Fibrosis Trials Register: 29 February 2012. SELECTION CRITERIA: Randomised
      controlled trials of macrolide antibiotics compared to: placebo; another class of
      antibiotic; another macrolide antibiotic; or the same macrolide antibiotic at a
      different dose. DATA COLLECTION AND ANALYSIS: Two authors independently extracted
      data and assessed risk of bias. Seven groups were contacted and provided
      additional data which were incorporated into the review. MAIN RESULTS: Ten of 31
      studies identified were included (959 patients). Five studies with a low risk of
      bias examined azithromycin versus placebo and demonstrated consistent improvement
      in forced expiratory volume in one second over six months (mean difference at six
      months 3.97% (95% confidence interval 1.74% to 6.19%; n = 549, from four
      studies)). Patients treated with azithromycin were approximately twice as likely
      to be free of pulmonary exacerbation at six months, odds ratio 1.96 (95%
      confidence interval 1.15 to 3.33). With respect to secondary outcomes, there was
      a significant reduction in need for oral antibiotics and greater weight gain in
      those taking azithromycin. Adverse events were uncommon and not obviously
      associated with azithromycin, although a once-weekly high dose regimen was
      associated with more frequent gastrointestinal adverse events. Treatment with
      azithromycin was associated with reduced identification of Staphylococcus aureus
      on respiratory culture, but also a significant increase in macrolide resistance.
      AUTHORS' CONCLUSIONS: This review provides evidence of improved respiratory
      function after six months of azithromycin. Data beyond six months were less
      clear, although reduction in pulmonary exacerbation was sustained. Treatment
      appeared safe over a six-month period; however, emergence of macrolide resistance
      was a concern. A multi-centre trial examining long-term effects of this
      antibiotic treatment is needed, especially for infants recognised through newborn
      screening.

PMID- 23152215
TI  - Vitamin E for Alzheimer's dementia and mild cognitive impairment.
AB  - BACKGROUND: Vitamin E is a dietary compound that functions as an antioxidant
      scavenging toxic free radicals. Evidence that free radicals may contribute to the
      pathological processes of cognitive impairment including Alzheimer's disease has
      led to interest in the use of vitamin E in the treatment of mild cognitive
      impairment (MCI) and Alzheimer's dementia (AD). OBJECTIVES: To assess the
      efficacy of vitamin E in the treatment of AD and prevention of progression of MCI
      to dementia. SEARCH METHODS: The Specialized Register of the Cochrane Dementia
      and Cognitive Improvement Group (ALOIS), The Cochrane Library, MEDLINE, EMBASE,
      PsycINFO, CINAHL, LILACS as well as many trials databases and grey literature
      sources were searched on 25 June 2012 using the terms: "Vitamin E", vitamin-E,
      alpha-tocopherol. SELECTION CRITERIA: All unconfounded, double-blind, randomised
      trials in which treatment with vitamin E at any dose was compared with placebo
      for patients with AD and MCI. DATA COLLECTION AND ANALYSIS: Two review authors
      independently applied the selection criteria and assessed study quality and
      extracted and analysed the data. For each outcome measure data were sought on
      every patient randomised. Where such data were not available an analysis of
      patients who completed treatment was conducted. It was not possible to pool data
      between studies owing to a lack of comparable outcome measure. MAIN RESULTS: Only
      three studies met the inclusion criteria: two in an AD population and one in an
      MCI population. In the first of the AD studies (Sano 1996) the authors reported
      some benefit from vitamin E (2000 IU/day) with fewer participants reaching an end
      point of death, institutionalisation, change to a Clinical Dementia Rating (CDR)
      of three, or loss of two basic activities of daily living within two years. Of
      patients completing treatment, 58% (45/77) on vitamin E compared with 74% (58/78)
      on placebo reached one of the end points (odds ratio (OR) 0.49; 95% confidence
      interval (CI) 0.25 to 0.96). The second AD treatment study (Lloret 2009) explored
      the effects of vitamin E (800 IU/day) on cognitive progression in relation to
      oxidative stress levels. Patients whose oxidative stress markers were lowered by
      vitamin E showed no significant difference in the percentage change in Mini
      Mental State Examination (MMSE) score, between baseline and six months, compared
      to the placebo group. The primary aim of the MCI study (Petersen 2005) was to
      investigate the effect of vitamin E (2000 IU/day) on the time to progression from
      MCI to possible or probable AD. A total of 214 of the 769 participants progressed
      to dementia, with 212 being classified as having possible or probable AD. There
      was no significant difference in the probability of progression from MCI to AD
      between the vitamin E group and the placebo group (hazard ratio 1.02; 95% CI 0.74
      to 1.41; P = 0.91). AUTHORS' CONCLUSIONS: No convincing evidence that vitamin E
      is of benefit in the treatment of AD or MCI. Future trials assessing vitamin E
      treatment in AD should not be restricted to alpha-tocopherol.

PMID- 23152216
TI  - Horse chestnut seed extract for chronic venous insufficiency.
AB  - BACKGROUND: Conservative therapy of chronic venous insufficiency (CVI) consists
      largely of compression treatment. However, this often causes discomfort and has
      been associated with poor compliance. Therefore, oral drug treatment is an
      attractive option. This is an update of a Cochrane review first published in 2002
      and updated in 2004, 2006, 2008 and 2010. OBJECTIVES: To review the efficacy and
      safety of oral horse chestnut seed extract (HCSE) versus placebo, or reference
      therapy, for the treatment of CVI. SEARCH METHODS: For this update the Cochrane
      Peripheral Vascular Diseases Review Group searched their Specialised Register
      (last searched June 2012) and CENTRAL (Issue 5, 2012). For the previous versions
      of the review the authors searched AMED (inception to July 2005) and Phytobase
      (inception to January 2001) for randomised controlled trials (RCTs) of HCSE for
      CVI. Manufacturers of HCSE preparations and experts on the subject were contacted
      for published and unpublished material. There were no restrictions on language.
      SELECTION CRITERIA: RCTs comparing oral HCSE mono-preparations with placebo, or
      reference therapy, in people with CVI. Trials assessing HCSE as one of several
      active components in a combination preparation, or as a part of a combination
      treatment, were excluded. DATA COLLECTION AND ANALYSIS: Both authors
      independently selected the studies and, using a standard scoring system, assessed
      methodological quality and extracted data. Disagreements concerning evaluation of
      individual trials were resolved through discussion. MAIN RESULTS: Overall, there
      appeared to be an improvement in CVI related signs and symptoms with HCSE
      compared with placebo. Leg pain was assessed in seven placebo-controlled trials.
      Six reported a significant reduction of leg pain in the HCSE groups compared with
      the placebo groups, while another reported a statistically significant
      improvement compared with baseline. One trial suggested a weighted mean
      difference (WMD) of 42.4 mm (95% confidence interval (CI) 34.9 to 49.9) measured
      on a 100 mm visual analogue scale. Leg volume was assessed in seven placebo
      controlled trials. Six trials (n = 502) suggested a WMD of 32.1ml (95% CI 13.49
      to 50.72) in favour of HCSE compared with placebo. One trial indicated that HCSE
      may be as effective as treatment with compression stockings. Adverse events were
      usually mild and infrequent. AUTHORS' CONCLUSIONS: The evidence presented
      suggests that HCSE is an efficacious and safe short-term treatment for CVI.
      However, several caveats exist and larger, definitive RCTs are required to
      confirm the efficacy of this treatment option.

PMID- 23152217
TI  - Ketamine as an adjuvant to opioids for cancer pain.
AB  - BACKGROUND: This is an update of the original review published in Issue 1, 2003.
      Ketamine is a commonly used anaesthetic agent, and in subanaesthetic doses is
      also given as an adjuvant to opioids for the treatment of cancer pain,
      particularly when opioids alone prove to be ineffective. Ketamine is known to
      have psychotomimetic (including hallucinogenic), urological and hepatic adverse
      effects. OBJECTIVES: To determine the effectiveness and adverse effects of
      ketamine as an adjuvant to opioids in the treatment of cancer pain. SEARCH
      METHODS: Studies were originally identified from MEDLINE (1966 to 2002), EMBASE
      (1980 to 2002), CancerLit (1966 to 2002), The Cochrane Library (Issue 1, 2001);
      by handsearching reference lists from review articles, trials, and chapters from
      standard textbooks on pain and palliative care. The manufacturer of ketamine
      (Pfizer Parke-Davis) provided search results from their in-house database,
      PARDLARS.An improved and updated search of the following was performed in May
      2012: CENTRAL, MEDLINE & OVID MEDLINE R, EMBASE. SELECTION CRITERIA: Randomized
      controlled trials (RCTs) of adult patients with cancer and pain being treated
      with an opioid, and receiving either ketamine (any dose and any route of
      administration) or placebo or an active control. Studies having a group size of
      at least 10 participants who completed the trial. DATA COLLECTION AND ANALYSIS:
      Two independent review authors identified four RCTs for possible inclusion in the
      review, and 32 case studies/case series reports. Quality and validity assessment
      was performed by three independent review authors, and two RCTs were excluded
      because of inappropriate study design. Patient-reported pain intensity and pain
      relief was assessed using visual analogue scales (VAS), verbal rating scales or
      other validated scales, and adverse effects data were collated. For the update
      three RCTs were identified for possible inclusion in the review. MAIN RESULTS:
      Three new studies were identified by the updated search. All three were excluded
      from the review. Two studies were eligible for inclusion in the original review
      and both concluded that ketamine improves the effectiveness of morphine in the
      treatment of cancer pain. However, pooling of the data was not appropriate
      because of the small total number of participants (30), and the presence of
      clinical heterogeneity. Some patients experienced hallucinations on both ketamine
      plus morphine and morphine alone and were treated successfully with diazepam. No
      other serious adverse effects were reported. AUTHORS' CONCLUSIONS: Since the last
      version of this review three new studies were identified but excluded from the
      review. Current evidence is insufficient to assess the benefits and harms of
      ketamine as an adjuvant to opioids for the relief of cancer pain. More RCTs are
      needed.

PMID- 23152218
TI  - Management of sexual dysfunction due to antipsychotic drug therapy.
AB  - BACKGROUND: Psychotropic drugs are associated with sexual dysfunction. Symptoms
      may concern penile erection, lubrication, orgasm, libido, retrograde ejaculation,
      sexual arousal, or overall sexual satisfaction. These are major aspects of
      tolerability and can highly affect patients' compliance. OBJECTIVES: To determine
      the effects of different strategies (e.g. dose reduction, drug holidays,
      adjunctive medication, switching to another drug) for treatment of sexual
      dysfunction due to antipsychotic therapy. SEARCH METHODS: An updated search was
      performed in the Cochrane Schizophrenia Group's Trials Register (3 May 2012) and
      the references of all identified studies for further trials. SELECTION CRITERIA:
      We included all relevant randomised controlled trials involving people with
      schizophrenia and sexual dysfunction. DATA COLLECTION AND ANALYSIS: We extracted
      data independently. For dichotomous data we calculated random effects risk ratios
      (RR) with 95% confidence intervals (CI), for crossover trials we calculated Odds
      Ratios (OR) with 95% CI. For continuous data, we calculated mean differences (MD)
      on the basis of a random-effects model. We analysed cross-over trials under
      consideration of correlation of paired measures. MAIN RESULTS: Currently this
      review includes four pioneering studies (total n = 138 , duration two weeks to
      four months), two of which are cross-over trials. One trial reported
      significantly more erections sufficient for penetration when receiving sildenafil
      compared with when receiving placebo (n = 32, MD 3.20 95% CI 1.83 to 4.57), a
      greater mean duration of erections (n = 32, MD 1.18 95% CI 0.52 to 1.84) and
      frequency of satisfactory intercourse (n = 32, MD 2.84 95% CI 1.61 to 4.07). The
      second trial found no evidence for selegiline as symptomatic treatment for
      antipsychotic-induced sexual dysfunction compared with placebo (n = 10, MD change
      on Aizenberg's sexual functioning scale -0.40 95% CI -3.95 to 3.15). No evidence
      was found for switching to quetiapine from risperidone to improve sexual
      functioning (n = 36, MD -2.02 95% CI -5.79 to 1.75). One trial reported
      significant improvement in sexual functioning when participants switched from
      risperidone or an typical antipsychotic to olanzapine (n = 54, MD -0.80 95% CI 
      1.55 to -0.05). AUTHORS' CONCLUSIONS: We are not confident that cross-over
      studies are appropriate for this participant group as they are best for
      conditions that are stable and for interventions with no physiological and
      psychological carry-over. Sildenafil may be a useful option in the treatment of
      antipsychotic-induced sexual dysfunction in men with schizophrenia, but this
      conclusion is based only on one small short trial. Switching to olanzapine may
      improve sexual functioning in men and women, but the trial assessing this was a
      small, open label trial. Further well designed randomised control trials that are
      blinded and well conducted and reported, which investigate the effects of dose
      reduction, drug holidays, symptomatic therapy and switching antipsychotic on
      sexual function in people with antipsychotic-induced sexual dysfunction are
      urgently needed.

PMID- 23152219
TI  - Techniques and materials for skin closure in caesarean section.
AB  - BACKGROUND: Caesarean section is a common operation with no agreed upon standard
      regarding certain operative techniques or materials to use. With regard to skin
      closure, the skin incision can be re-approximated by a subcuticular suture
      immediately below the skin layer, by an interrupted suture, or by staples. A
      great variety of materials and techniques are used for skin closure after
      caesarean section and there is a need to identify which provide the best outcomes
      for women. OBJECTIVES: To compare the effects of skin closure techniques and
      materials on maternal and operative outcomes after caesarean section. SEARCH
      METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials
      Register (10 January 2012). SELECTION CRITERIA: All randomized trials comparing
      different skin closure materials in caesareans were selected. Two review authors
      independently abstracted the data. DATA COLLECTION AND ANALYSIS: We identified 19
      trials and included 11, but only eight trials contributed data. Three trials were
      not randomized controlled trials; two were ongoing; one study was terminated and
      the results were not available for review; one is awaiting classification; and
      one did not compare skin closure materials, but rather suture to suture and drain
      placement. MAIN RESULTS: The two methods of skin closure for caesarean that have
      been most often compared are non-absorbable staples and absorbable subcutaneous
      sutures. Compared with absorbable subcutaneous sutures, non-absorbable staples
      are associated with similar incidences of wound infection. Other important
      secondary outcomes, such as wound complications, were also similar between the
      groups in women with Pfannenstiel incisions. However, it is important to note,
      that for both of these outcomes (wound infection and wound complication), staples
      may have a differential effect depending on the type of skin incision, i.e.,
      Pfannenstiel or vertical. Compared with absorbable subcutaneous sutures, non
      absorbable staples are associated with an increased risk of skin separation, and
      therefore, reclosure. However, skin separation was variably defined across
      trials, and most staples were removed before four days postpartum. AUTHORS'
      CONCLUSIONS: There is currently no conclusive evidence about how the skin should
      be closed after caesarean section. Staples are associated with similar outcomes
      in terms of wound infection, pain and cosmesis compared with sutures, and these
      two are the most commonly studied methods for skin closure after caesarean
      section. If staples are removed on day three, there is an increased incidence of
      skin separation and the need for reclosure compared with absorbable sutures.

PMID- 23152220
TI  - Herbal medicines for viral myocarditis.
AB  - BACKGROUND: Herbal medicines are being used as a treatment for viral diseases
      such as viral myocarditis and numerous clinical trials have been conducted to
      investigate their efficacy. Despite this wealth of evidence, the role of herbal
      medicines in the treatment of viral myocarditis is yet to be established. This is
      an update of the review published in 2010. OBJECTIVES: To assess the effects of
      herbal medicines on clinical (for example mortality, incidence of complications)
      and indirect outcomes (for example cardiac function, biochemical response) in
      patients with viral myocarditis. SEARCH METHODS: We searched CENTRAL (The
      Cochrane Library 2011, Issue 2), MEDLINE (January 1966 to June 2011), EMBASE
      (January 1998 to June 2011), Chinese Biomedical Database (1979 to 2011), China
      National Knowledge Infrastructure (1979 to 2011), Chinese VIP Information (1989
      to 2011), Chinese Academic Conference Papers Database and Chinese Dissertation
      Database (1980 to 2011), AMED (June 2011), LILACS (June 2011), and the Cochrane
      Complementary Medicine Field Trials Register. We handsearched Chinese journals
      and conference proceedings. No language restrictions were applied. SELECTION
      CRITERIA: Randomised controlled trials of herbal medicines (with a minimum of
      seven days treatment duration) compared with placebo, no intervention, or
      conventional interventions were included. Trials of herbal medicine plus
      conventional drug versus drug alone were also included. Only trials that reported
      an adequate description of allocation sequence generation were included. DATA
      COLLECTION AND ANALYSIS: Two review authors independently extracted data and
      evaluated trial quality. Adverse effects information was collected from the
      trials. MAIN RESULTS: Twenty randomised controlled trials involving 2177 people
      were included. All trials were conducted and published in China. The controls
      included anti-arrhythmic drugs, corticosteroids, and antiviral therapies such as
      ribavirin or interferon. Combining the risk of bias on random sequence
      generation, allocation concealment, selective reporting, and incomplete outcome
      data, the included trials were assessed to be at high risk of bias. Thirteen
      different herbal medicines were tested in the included trials. None of the trials
      reported outcomes on mortality. The trials reported electrocardiogram results,
      level of myocardial enzymes, cardiac function, and adverse effects.A meta
      analysis showed a significant effect of Astragalus membranaceus injection plus
      supportive therapy on the number of patients with an abnormal electrocardiogram
      (RR 0.28, 95% CI 0.13 to 0.61), ST-T changes (RR 0.72, 95% CI 0.54 to 0.95),
      creatine phosphate kinase (CPK) levels (MD -21.54, 95% CI -33.80 to -9.28), and
      lactate dehydrogenase (LDH) levels (MD -30.33, 95% CI -46.78 to -13.88).Shengmai
      injection plus supportive therapy showed a significant effect on the number of
      patients with an abnormal electrocardiogram (RR 0.11, 95% CI 0.01 to 0.86), CPK
      levels (MD -103.90, 95% CI -114.97 to -92.83), LDH levels (MD -34.60, 95% CI 
      51.25 to -17.95), and on myocardial enzyme CK-MB levels (MD -10.87, 95% CI -14.50
      to -7.24). Shengmai decoction plus supportive therapy showed a significant effect
      on improving quality of life measured by the SF-36 (MD 40.20, 95% CI 18.13 to
      62.27) compared to supportive therapy. Data on adverse events were only available
      from six of the included trials and no serious adverse effects were reported.
      AUTHORS' CONCLUSIONS: Some herbal medicines may lead to improvement of
      ventricular premature beat, electrocardiogram, level of myocardial enzymes, and
      cardiac function in viral myocarditis. However, these findings should be
      interpreted with care due to the high risk of bias of the included studies, small
      sample size, and limited number of trials on individual herbs. Further robust
      trials are needed to explore the use of herbal medicines in viral myocarditis.

PMID- 23152221
TI  - Antibiotics to prevent complications following tooth extractions.
AB  - BACKGROUND: The most frequent indications for tooth extractions are dental caries
      and periodontal infections, and these extractions are generally done by general
      dental practitioners. Antibiotics may be prescribed to patients undergoing
      extractions to prevent complications due to infection. OBJECTIVES: To determine
      the effect of antibiotic prophylaxis on the development of infectious
      complications following tooth extractions. SEARCH METHODS: The following
      electronic databases were searched: the Cochrane Oral Health Group's Trials
      Register (to 25 January 2012), the Cochrane Central Register of Controlled Trials
      (CENTRAL) (The Cochrane Library 2012, Issue 1), MEDLINE via OVID (1948 to 25
      January 2012), EMBASE via OVID (1980 to 25 January 2012) and LILACS via BIREME
      (1982 to 25 January 2012). There were no restrictions regarding language or date
      of publication. SELECTION CRITERIA: We included randomised double-blind placebo
      controlled trials of antibiotic prophylaxis in patients undergoing tooth
      extraction(s) for any indication. DATA COLLECTION AND ANALYSIS: Two review
      authors independently assessed risk of bias for the included studies and
      extracted data. We contacted trial authors for further details where these were
      unclear. For dichotomous outcomes we calculated risk ratios (RR) and 95%
      confidence intervals (CI) using random-effects models. For continuous outcomes we
      used mean differences (MD) with 95% CI using random-effects models. We examined
      potential sources of heterogeneity. The quality of the body of evidence has been
      assessed using the GRADE tool. MAIN RESULTS: This review included 18 double-blind
      placebo-controlled trials with a total of 2456 participants. Five trials were
      assessed at unclear risk of bias, thirteen at high risk, and none at low risk of
      bias. Compared to placebo, antibiotics probably reduce the risk of infection in
      patients undergoing third molar extraction(s) by approximately 70% (RR 0.29 (95%
      CI 0.16 to 0.50) P < 0.0001, 1523 participants, moderate quality evidence) which
      means that 12 people (range 10-17) need to be treated with antibiotics to prevent
      one infection following extraction of impacted wisdom teeth. There is evidence
      that antibiotics may reduce the risk of dry socket by 38% (RR 0.62 (95% CI 0.41
      to 0.95) P = 0.03, 1429 participants, moderate quality evidence) which means that
      38 people (range 24-250) need to take antibiotics to prevent one case of dry
      socket following extraction of impacted wisdom teeth. There is also some evidence
      that patients who have prophylactic antibiotics may have less pain (MD -8.17 (95%
      CI -11.90 to -4.45) P < 0.0001, 372 participants, moderate quality evidence )
      overall 7 days after the extraction compared to those receiving placebo, which
      may be a direct result of the lower risk of infection. There is no evidence of a
      difference between antibiotics and placebo in the outcomes of fever (RR 0.34, 95%
      CI 0.06 to 1.99), swelling (RR 0.92, 95% CI 0.65 to 1.30) or trismus (RR 0.84,
      95% CI 0.42 to 1.71) 7 days after tooth extraction.Antibiotics are associated
      with an increase in generally mild and transient adverse effects compared to
      placebo (RR 1.98 (95% CI 1.10 to 3.59) P = 0.02) which means that for every 21
      people (range 8-200) who receive antibiotics, an adverse effect is likely.
      AUTHORS' CONCLUSIONS: Although general dentists perform dental extractions
      because of severe dental caries or periodontal infection, there were no trials
      identified which evaluated the role of antibiotic prophylaxis in this group of
      patients in this setting. All of the trials included in this review included
      healthy patients undergoing extraction of impacted third molars, often performed
      by oral surgeons. There is evidence that prophylactic antibiotics reduce the risk
      of infection, dry socket and pain following third molar extraction and result in
      an increase in mild and transient adverse effects. It is unclear whether the
      evidence in this review is generalisable to those with concomitant illnesses or
      immunodeficiency, or those undergoing the extraction of teeth due to severe
      caries or periodontitis. However, patients at a higher risk of infection are more
      likely to benefit from prophylactic antibiotics, because infections in this group
      are likely to be more frequent, associated with complications and be more
      difficult to treat. Due to the increasing prevalence of bacteria which are
      resistant to treatment by currently available antibiotics, clinicians should
      consider carefully whether treating 12 healthy patients with antibiotics to
      prevent one infection is likely to do more harm than good.

PMID- 23152222
TI  - Surgical treatment of fibroids for subfertility.
AB  - BACKGROUND: Fibroids are the most common benign tumours of the female genital
      tract and are associated with numerous clinical problems including a possible
      negative impact on fertility. In women requesting preservation of fertility,
      fibroids can be surgically removed (myomectomy) by laparotomy, laparoscopically
      or hysteroscopically depending on the size, site and type of fibroid. Myomectomy
      is however a procedure that is not without risk and can result in serious
      complications. It is therefore essential to determine whether such a procedure
      can result in an improvement in fertility and, if so, to then determine the ideal
      surgical approach. OBJECTIVES: To examine the effect of myomectomy on fertility
      outcomes and to compare different surgical approaches. SEARCH METHODS: We
      searched the Cochrane Menstrual Disorders and Subfertility Group (MDSG)
      Specialised Register, Cochrane Central Register of Controlled Trials (CENTRAL),
      MEDLINE, EMBASE, PsycINFO, CINAHL, Database of Abstracts of Reviews of Effects
      (DARE), LILACS, conference abstracts on the ISI Web of Knowledge, OpenSigle for
      grey literature from Europe, and ongoing clinical trials registered online. The
      final search was in June 2012. SELECTION CRITERIA: Randomised controlled trials
      examining the effect of myomectomy compared to no intervention or where different
      surgical approaches are compared regarding the effect on fertility outcomes in a
      group of infertile women suffering from uterine fibroids. DATA COLLECTION AND
      ANALYSIS: Data collection and analysis were conducted in accordance with the
      procedure suggested in the Cochrane Handbook for Systematic Reviews of
      Interventions. MAIN RESULTS: One study examined the effect of myomectomy on
      reproductive outcomes and showed no evidence for a significant effect on the
      clinical pregnancy rate for intramural (OR 1.88, 95% CI 0.57 to 6.14), submucous
      (OR 2.04, 95% CI 0.62 to 6.66), combined intramural and subserous (OR 2.00, 95%
      CI 0.40 to 10.09) and combined intramural submucous fibroids (OR 3.24, 95% CI
      0.72 to 14.57). Similarly, there was no evidence for a significant effect of
      myomectomy for any of the described types of fibroids on the miscarriage rate
      (intramural fibroids OR 0.89 (95% CI 0.14 to 5.48), submucous fibroids OR 0.63
      (95% CI 0.09 to 4.40), combined intramural and subserous fibroids OR 0.25 (95% CI
      0.01 to 4.73) and combined intramural submucous fibroids OR 0.50 (95% CI 0.03 to
      7.99).Two studies compared open versus laparoscopic myomectomy and found no
      evidence for a significant effect on the live birth rate (OR 0.80, 95% CI 0.42 to
      1.50), clinical pregnancy rate (OR 0.96, 95% CI 0.52 to 1.78), ongoing pregnancy
      rate (OR 1.61, 95% CI 0.26 to 10.04), miscarriage rate (OR 1.31, 95% CI 0.40 to
      4.27), preterm labour rate (OR 0.68, 95% CI 0.11 to 4.43) and caesarean section
      rate (OR 0.59, 95% CI 0.13 to 2.72). AUTHORS' CONCLUSIONS: There is currently
      insufficient evidence from randomised controlled trials to evaluate the role of
      myomectomy to improve fertility. Regarding the surgical approach to myomectomy,
      current evidence from two randomised controlled trials suggests there is no
      significant difference between the laparoscopic and open approach regarding
      fertility performance. This evidence needs to be viewed with caution due to the
      small number of studies. Finally, there is currently no evidence from randomised
      controlled trials regarding the effect of hysteroscopic myomectomy on fertility
      outcomes.

PMID- 23152223
TI  - Perioperative increase in global blood flow to explicit defined goals and
      outcomes following surgery.
AB  - BACKGROUND: Studies have suggested that increasing whole body blood flow and
      oxygen delivery around the time of surgery reduces mortality, morbidity and the
      expense of major operations. OBJECTIVES: To describe the effects of increasing
      perioperative blood flow using fluids with or without inotropes or vasoactive
      drugs. Outcomes were mortality, morbidity, resource utilization and health
      status. SEARCH METHODS: We searched CENTRAL (The Cochrane Library 2012, Issue 1),
      MEDLINE (1966 to March 2012) and EMBASE (1982 to March 2012). We manually
      searched the proceedings of major conferences and personal reference databases up
      to December 2011. We contacted experts in the field and pharmaceutical companies
      for published and unpublished data. SELECTION CRITERIA: We included randomized
      controlled trials with or without blinding. We included studies involving adult
      patients (aged 16 years or older) undergoing surgery (patients having a procedure
      in an operating room). The intervention met the following criteria.
      'Perioperative' was defined as starting up to 24 hours before surgery and
      stopping up to six hours after surgery. 'Targeted to increase global blood flow'
      was defined by explicit measured goals that were greater than in controls,
      specifically one or more of cardiac index, oxygen delivery, oxygen consumption,
      stroke volume (and the respective derived indices), mixed venous oxygen
      saturation (SVO(2)), oxygen extraction ratio (0(2)ER) or lactate. DATA COLLECTION
      AND ANALYSIS: Two authors independently extracted the data. We contacted study
      authors for additional data. We used Review Manager software. MAIN RESULTS: We
      included 31 studies of 5292 participants. There was no difference in mortality:
      282/2615 (10.8%) died in the control group and 238/2677 (8.9%) in the treatment
      group, RR of 0.89 (95% CI 0.76 to 1.05, P = 0.18). However, the results were
      sensitive to analytical methods and the intervention was better than control when
      inverse variance or Mantel-Haenszel random-effects models were used, RR of 0.72
      (95% CI 0.55 to 0.95, P = 0.02). The results were also sensitive to withdrawal of
      studies with methodological limitations. The rates of three morbidities were
      reduced by increasing global blood flow: renal failure, RR of 0.71 (95% CI 0.57
      to 0.90); respiratory failure, RR of 0.51 (95% CI 0.28 to 0.93); and wound
      infections, RR of 0.65 (95% CI 0.51 to 0.84). There were no differences in the
      rates of nine other morbidities: arrhythmia, pneumonia, sepsis, abdominal
      infection, urinary tract infection, myocardial infarction, congestive cardiac
      failure or pulmonary oedema, or venous thrombosis. The number of patients with
      complications was reduced by the intervention, RR of 0.68 (95% CI 0.58 to 0.80).
      Hospital length of stay was reduced in the treatment group by a mean of 1.16 days
      (95% CI 0.43 to 1.89, P = 0.002). There was no difference in critical care length
      of stay. There were insufficient data to comment on quality of life and cost
      effectiveness. AUTHORS' CONCLUSIONS: It remains uncertain whether increasing
      blood flow using fluids, with or without inotropes or vasoactive drugs, reduces
      mortality in adults undergoing surgery. The primary analysis in this review
      (mortality at longest follow-up) showed no difference between the intervention
      and control, but this result was sensitive to the method of analysis, the
      withdrawal of studies with methodological limitations, and is dominated by a
      single large RCT. Overall, for every 100 patients in whom blood flow is increased
      perioperatively to defined goals, one can expect 13 in 100 patients (from 40/100
      to 27/100) to avoid a complication, 2/100 to avoid renal impairment (from 8/100
      to 6/100), 5/100 to avoid respiratory failure (from 10/100 to 5/100), and 4/100
      to avoid postoperative wound infection (from 10/100 to 6/100). On average,
      patients receiving the intervention stay in hospital one day less. It is unlikely
      that the intervention causes harm. The balance of current evidence does not
      support widespread implementation of this approach to reduce mortality but does
      suggest that complications and duration of hospital stay are reduced.

PMID- 23152224
TI  - Rectal 5-aminosalicylic acid for maintenance of remission in ulcerative colitis.
AB  - BACKGROUND: 5-Aminosalicylic acid (5-ASA) is a first-line therapy for inducing
      and maintaining remission of mild and moderately active ulcerative colitis (UC).
      When the proximal margin of inflammation is distal to the splenic flexure, 5-ASA
      therapy can be delivered as a rectal suppository, foam or liquid enema.
      OBJECTIVES: The primary objective was to assess the efficacy and safety of rectal
      5-ASA for maintaining remission of distal UC. SEARCH METHODS: We searched MEDLINE
      (1966 to August 2012), the Cochrane Library (August 2012), abstracts from major
      gastroenterology meetings (1997-2011) and bibliographies of relevant publications
      to identify relevant studies. SELECTION CRITERIA: Eligible studies were
      randomized controlled trials comparing rectal 5-ASA to placebo or another active
      treatment for a minimum duration of six months. Symptom scores needed to be
      assessed in at least one study outcome. Patients had to be at least 12 years of
      age with disease extent less than 60 cm from the anal verge or distal to the
      splenic flexure, as determined by barium enema, colonoscopy or sigmoidoscopy.
      Patients were expected to be in remission prior to the treatment trial. DATA
      COLLECTION AND ANALYSIS: Study eligibility was independently assessed by three
      authors. Data were extracted using standardized forms by two independent
      reviewers, with inter-rater agreement assessed using Cohen's Kappa and
      disagreements resolved by consensus. In cases where clarification of study
      results or methodology was needed, corresponding authors were contacted. The
      methodological quality of each trial was assessed by the Cochrane risk of bias
      tool and by a 30-point scale developed and used previously by the authors. Pooled
      risk ratios (RR) and corresponding 95% confidence intervals (CI) for continued
      clinical, endoscopic and histologic remission were estimated for comparisons
      between rectal 5-ASA and placebo or oral 5-ASA, and for comparisons among 5-ASA
      doses. Heterogeneity was assessed using the Chi(2) test and visual inspection of
      forest plots. If no significant heterogeneity was identified (P > 0.10 for
      Chi(2)) a fixed-effect model (Mantel-Haenstzel) was used. If heterogeneity was
      significant, a random-effects model was used. MAIN RESULTS: Nine studies (484
      patients) met the pre-specified inclusion criteria (Kappa 1.00). Six studies were
      rated as low risk of bias. Three studies were rated as high risk of bias due to
      blinding (two open label and one single-blind). The total daily dose of rectal 5
      ASA ranged from 0.5 g to 4 g, and dose frequency ranged from once to three times
      daily. 5-ASA was delivered as liquid enema in five studies or as a suppository in
      four studies. Follow-up ranged from 6 to 24 months. Rectal 5-ASA was
      significantly superior to placebo for maintenance of symptomatic remission over a
      period of 12 months.Sixty-two per cent of patients in the rectal 5-ASA group
      maintained symptomatic remission compared to 30% of patients in the placebo group
      (4 studies; 301 patients; RR 2.22, 95% CI 1.26 to 3.90; I(2) = 67%; P < 0.01). A
      GRADE analysis indicated that the overall quality of the evidence for the primary
      outcome was low due to imprecision (i.e. sparse data 144 events) and
      inconsistency (i.e. unexplained heterogeneity). Rectal 5-ASA was significantly
      superior to placebo for maintenance of endoscopic remission over a 12 month
      period. Seventy-five per cent of patients in the rectal 5-ASA group maintained
      endoscopic remission compared to 15% of patients in the placebo group (1 study;
      25 patients; RR 4.88, 95% CI 1.31 to 18.18; P < 0.05). There was no statistically
      significant difference in the proportion of patients who experienced at least one
      adverse event. Sixteen per cent of patients in the rectal 5-ASA group experienced
      at least one adverse compared to 12% of placebo patients (2 studies; 160
      patients; RR 1.35, 95% CI 0.63 to 2.89; I(2) = 0%; P = 0.44). The most commonly
      reported adverse events were anal irritation and abdominal pain. No statistically
      significant differences between rectal and oral 5-ASA were identified for either
      symptomatic or endoscopic remission over a period of six months. Eighty per cent
      of patients in the rectal 5-ASA group maintained symptomatic remission compared
      to 65% of patients in the oral 5-ASA group (2 studies; 69 patients; RR 1.24, 95%
      CI 0.92 to 1.66; I(2) = 0%; P = 0.15). A GRADE analysis indicated that the
      overall quality of the evidence for the primary outcome was low due to
      imprecision (i.e. sparse data 50 events) and high risk of bias (i.e. both studies
      in the pooled analysis were open label). Eighty per cent of patients in the
      rectal 5-ASA group maintained endoscopic remission compared to 70% of patients in
      the oral 5-ASA group (2 studies; 91 patients; RR 1.14, 95% CI 0.90 to 1.45; I(2)
      = 0%; P = 0.26). In two small trials, one comparing 2 g/day 5-ASA enemas to 4
      g/day 5-ASA enemas and the other comparing 0.5 g/day 5-ASA suppositories to 1
      g/day 5-ASA suppositories no dose response relationship was observed. AUTHORS'
      CONCLUSIONS: The limited data available suggest that rectal 5-ASA is effective
      and safe for maintenance of remission of mild to moderately active distal UC.
      Well designed randomized trials are needed to establish the optimal dosing
      regimen for rectal 5-ASA, to compare rectal 5-ASA with rectal corticosteroids and
      to identify subgroups of patients who are more or less responsive to specific
      rectal 5-ASA regimens. The combination of oral and rectal 5-ASA appears to be
      more effective than either oral or rectal monotherapy for induction of remission.
      The efficacy of combination therapy for maintenance of remission has not been
      assessed and could be evaluated in future trials.

PMID- 23152225
TI  - Hyperbaric oxygen therapy for promoting fracture healing and treating fracture
      non-union.
AB  - BACKGROUND: Hyperbaric oxygen therapy (HBOT) consists of intermittently
      administering 100% oxygen at pressures greater than one atmosphere absolute (ATA)
      in a pressure vessel. This technology has been used to treat a variety of
      diseases and has been described as helping patients who have delayed healing or
      established non-union of bony fractures. This is an update of a Cochrane Review
      first published in 2005, and previously updated in 2008. OBJECTIVES: The aim of
      this review is to assess the evidence for the benefit of hyperbaric oxygen
      treatment (HBOT) for the treatment of delayed bony healing and established non
      union of bony fractures. SEARCH METHODS: We searched the Cochrane Bone, Joint and
      Muscle Trauma Group Specialised Register (July 2012), the Cochrane Register of
      Controlled Trials (CENTRAL) (The Cochrane Library 2012, Issue 7), MEDLINE (1946
      to July Week 1 2012), EMBASE (1974 to 2012 July 16), CINAHL (1937 to 17 July
      2012), the Database of Randomised Controlled Trials in Hyperbaric Medicine
      (accessed July 2012), the WHO International Clinical Trials Registry Platform (17
      July 2012) and reference lists of articles. SELECTION CRITERIA: We aimed to
      include all randomised controlled trials comparing the clinical effects of HBOT
      with no HBOT (no treatment or sham) for healing of bony fractures and fracture
      non-unions. DATA COLLECTION AND ANALYSIS: Two review authors independently
      screened electronic search results, and all three authors independently performed
      study selection. We planned independent data collection and risk of bias
      assessment by two authors using standardised forms. MAIN RESULTS: No trials met
      the inclusion criteria. In this update, we identified three ongoing randomised
      controlled trials. Among the eight excluded studies were three randomised trials
      comparing HBOT with no treatment that included patients with fractures. One of
      these trials had been abandoned and the other two did not report on fracture
      healing outcomes. AUTHORS' CONCLUSIONS: This systematic review failed to locate
      any relevant clinical evidence to support or refute the effectiveness of HBOT for
      the management of delayed union or established non-union of bony fractures. Good
      quality clinical trials are needed to define the role, if any, of HBOT in the
      treatment of these injuries. There are three randomised controlled trials
      underway and we anticipate these will help provide some relevant clinical
      evidence to address this issue in the future.

PMID- 23152226
TI  - Drug therapy for delirium in terminally ill adult patients.
AB  - BACKGROUND: Delirium is a syndrome characterised by a disturbance of
      consciousness (often fluctuating), cognition and perception. In terminally ill
      patients it is one of the most common causes of admission to clinical care.
      Delirium may arise from any number of causes and treatment should be directed at
      addressing these causes rather than the symptom cluster. In cases where this is
      not possible, or treatment does not prove successful, the use of drug therapy to
      manage the symptoms may become necessary. This is an update of the review
      published on 'Drug therapy for delirium in terminally ill adult patients' in The
      Cochrane Library 2004, Issue 2 ( Jackson 2004). OBJECTIVES: To evaluate the
      effectiveness of drug therapies to treat delirium in adult patients in the
      terminal phase of a disease. SEARCH METHODS: We searched the following sources:
      CENTRAL (The Cochrane Library 2012, Issue 7), MEDLINE (1966 to 2012), EMBASE
      (1980 to 2012), CINAHL (1982 to 2012) and PSYCINFO (1990 to 2012). SELECTION
      CRITERIA: Prospective trials with or without randomisation or blinding involving
      the use of drug therapies for the treatment of delirium in adult patients in the
      terminal phase of a disease. DATA COLLECTION AND ANALYSIS: Two authors
      independently assessed trial quality using standardised methods and extracted
      trial data. We collected outcomes related to efficacy and adverse effects. MAIN
      RESULTS: One trial met the criteria for inclusion. In the 2012 update search we
      retrieved 3066 citations but identified no new trials. The included trial
      evaluated 30 hospitalised AIDS patients receiving one of three agents:
      chlorpromazine, haloperidol and lorazepam. The trial under-reported key
      methodological features. It found overall that patients in the chlorpromazine
      group and those in the haloperidol group had fewer symptoms of delirium at follow
      up (to below the diagnostic threshold using the Diagnostic and Statistical Manual
      of Mental Disorders (DSM-III) and that both were equally effective (at two days
      mean difference (MD) 0.37; 95% confidence interval (CI) -4.58 to 5.32; between
      two and six days MD -0.21; 95% CI -5.35 to 4.93). Chlorpromazine and haloperidol
      were found to be no different in improving cognitive status in the short term (at
      48 hours) but at subsequent follow-up cognitive status was reduced in those
      taking chlorpromazine. Improvements from baseline to day two for patients
      randomised to lorazepam were not apparent. All patients on lorazepam (n = 6)
      developed adverse effects, including oversedation and increased confusion,
      leading to trial drug discontinuation. AUTHORS' CONCLUSIONS: There remains
      insufficient evidence to draw conclusions about the role of drug therapy in the
      treatment of delirium in terminally ill patients. Thus, practitioners should
      continue to follow current clinical guidelines. Further research is essential.

PMID- 23152227
TI  - Newer generation antidepressants for depressive disorders in children and
      adolescents.
AB  - BACKGROUND: Depressive disorders are common in young people and are associated
      with significant negative impacts. Newer generation antidepressants, particularly
      selective serotonin reuptake inhibitors (SSRIs), are often used, however evidence
      of their effectiveness in children and adolescents is not clear. Furthermore,
      there have been warnings against their use in this population due to concerns
      about increased risk of suicidal ideation and behaviour. OBJECTIVES: To determine
      the efficacy and adverse outcomes, including definitive suicidal behaviour and
      suicidal ideation, of newer generation antidepressants compared with placebo in
      the treatment of depressive disorders in children and adolescents. SEARCH
      METHODS: For this update of the review, we searched the Cochrane Depression,
      Anxiety and Neurosis Review Group's Specialised Register (CCDANCTR) to October
      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 searched clinical trial registries and pharmaceutical company
      websites. We checked reference lists of included trials and other reviews, and
      sent letters to key researchers and the pharmaceutical companies of included
      trials from January to August 2011. SELECTION CRITERIA: Published and unpublished
      randomised controlled trials (RCTs), cross-over trials and cluster trials
      comparing a newer generation antidepressant with a placebo in children and
      adolescents aged 6 to 18 years old and diagnosed with a depressive disorder were
      eligible for inclusion. In this update, we amended the selection criteria to
      include newer generation antidepressants rather than SSRIs only. DATA COLLECTION
      AND ANALYSIS: Two or three review authors selected the trials, assessed their
      quality, and extracted trial and outcome data. We used a random-effects meta
      analysis. We used risk ratio (RR) to summarise dichotomous outcomes and mean
      difference (MD) to summarise continuous measures. MAIN RESULTS: Nineteen trials
      of a range of newer antidepressants compared with placebo, containing 3335
      participants, were included. The trials excluded young people at high risk of
      suicide and many co-morbid conditions and the participants are likely to be less
      unwell than those seen in clinical practice. We judged none of these trials to be
      at low risk of bias, with limited information about many aspects of risk of bias,
      high drop out rates and issues regarding measurement instruments and the clinical
      usefulness of outcomes, which were often variously defined across trials.
      Overall, there was evidence that those treated with an antidepressant had lower
      depression severity scores and higher rates of response/remission than those on
      placebo. However, the size of these effects was small with a reduction in
      depression symptoms of 3.51 on a scale from 17 to 113 (14 trials; N = 2490; MD 
      3.51; 95% confidence interval (CI) -4.55 to -2.47). Remission rates increased
      from 380 per 1000 to 448 per 1000 for those treated with an antidepressant. There
      was evidence of an increased risk (58%) of suicide-related outcome for those on
      antidepressants compared with a placebo (17 trials; N = 3229; RR 1.58; 95% CI
      1.02 to 2.45). This equates to an increased risk in a group with a median
      baseline risk from 25 in 1000 to 40 in 1000. Where rates of adverse events were
      reported, this was higher for those prescribed an antidepressant. There was no
      evidence that the magnitude of intervention effects (compared with placebo) were
      modified by individual drug class. AUTHORS' CONCLUSIONS: Caution is required in
      interpreting the results given the methodological limitations of the included
      trials in terms of internal and external validity. Further, the size and clinical
      meaningfulness of statistically significant results are uncertain. However, given
      the risks of untreated depression in terms of completed suicide and impacts on
      functioning, if a decision to use medication is agreed, then fluoxetine might be
      the medication of first choice given guideline recommendations. Clinicians need
      to keep in mind that there is evidence of an increased risk of suicide-related
      outcomes in those treated with antidepressant medications.

PMID- 23152228
TI  - Multiple-micronutrient supplementation for women during pregnancy.
AB  - BACKGROUND: Multiple-micronutrient deficiencies often coexist in low- to middle
      income countries. They are exacerbated in pregnancy due to the increased demands,
      leading to potentially adverse effects on the mother. Substantive evidence
      regarding the effectiveness of multiple-micronutrient supplements (MMS) during
      pregnancy is not available. OBJECTIVES: To evaluate the benefits to both mother
      and infant of multiple-micronutrient supplements in pregnancy and to assess the
      risk of adverse events as a result of supplementation. SEARCH METHODS: We
      searched the Cochrane Pregnancy and Childbirth Group's Trials Register (17
      February 2012) and reference lists of retrieved articles and key reviews. We also
      contacted experts in the field for additional and ongoing trials. SELECTION
      CRITERIA: All prospective randomised controlled trials evaluating multiple
      micronutrient supplementation during pregnancy and its effects on the pregnancy
      outcome, irrespective of language or publication status of the trials. We
      included cluster-randomised trials but quasi-randomised trials were excluded.
      DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trials
      for inclusion and trial quality. Two review authors independently extracted the
      data. Data were checked for accuracy. MAIN RESULTS: Twenty-three trials
      (involving 76,532 women) were identified as eligible for inclusion in this review
      but only 21 trials (involving 75,785 women) contributed data to the review.When
      compared with iron and folate supplementation, MMS resulted in a statistically
      significant decrease in the number of low birthweight babies (risk ratio (RR)
      0.89; 95% confidence interval (CI) 0.83 to 0.94) and small-for-gestational age
      (SGA) babies (RR 0.87; 95% CI 0.81 to 0.95). No statistically significant
      differences were shown for other maternal and pregnancy outcomes: preterm births
      RR 0.99 (95% CI 0.96 to 1.02), miscarriage RR 0.90 (95% CI 0.79 to 1.02),
      maternal mortality RR 0.97 (95% CI 0.63 to 1.48), perinatal mortality RR 0.99
      (95% CI 0.84 to 1.16), stillbirths RR 0.96 (95% CI 0.86 to 1.07) and neonatal
      mortality RR 1.01 (95% CI 0.89 to 1.15).A number of prespecified clinically
      important outcomes could not be assessed due to insufficient or non-available
      data. These include placental abruption, congenital anomalies including neural
      tube defects, premature rupture of membranes, neurodevelopmental delay, very
      preterm births, cost of supplementation, side-effects of supplements, maternal
      well being or satisfaction, and nutritional status of children. AUTHORS'
      CONCLUSIONS: Though multiple micronutrients have been found to have a significant
      beneficial impact on SGA and low birthweight babies, we still need more evidence
      to guide a universal policy change and to suggest replacement of routine iron and
      folate supplementation with a MMS. Future trials should be adequately powered to
      evaluate the effects on mortality and other morbidity outcomes. Trials should
      also assess the effect of variability between different combinations and dosages
      of micronutrients, keeping within the safe recommended levels. In regions with
      deficiency of a single micronutrient, evaluation of each micronutrient against a
      placebo in women already receiving iron with folic acid would be especially
      useful in justifying the inclusion of that micronutrient in routine antenatal
      care.

PMID- 23152229
TI  - Shengmai (a traditional Chinese herbal medicine) for heart failure.
AB  - BACKGROUND: This systemic review is an update of a review previously published in
      2011. Heart failure is a major public health problem worldwide. Shengmai (a
      traditional Chinese herbal medicine) has long been used as a complementary
      treatment for heart failure in China. OBJECTIVES: To assess the effects (both
      benefits and harms) of Shengmai for heart failure. SEARCH METHODS: We searched
      CENTRAL and DARE on The Cochrane Library (2011, Issue 1), MEDLINE (1948 to March
      2011), EMBASE (1980 to March 2011), AMED (1985 to August 2008) (AMED was not
      searched for the update as it is no longer available to the person conducting the
      searches), BIOSIS (1969 to March 2011), CBM (1978 to April 2011), VIP (1989 to
      April 2011) and CNKI (1979 to April 2011). We also handsearched Chinese journals.
      No language restrictions were applied. SELECTION CRITERIA: Randomized controlled
      trials (RCTs) of Shengmai plus usual treatment versus usual treatment alone or
      Shengmai versus placebo in treating heart failure, irrespective of blinding
      status, were included. More stringent inclusion criteria were applied in this
      update and only studies with a clear description of randomization methods and
      classified as true RCTs were included. DATA COLLECTION AND ANALYSIS: Two authors
      independently selected trials, assessed methodological quality and extracted
      data. Dichotomous and continuous data were calculated as relative risk (RR) and
      mean difference (MD) or standardized mean difference (SMD), respectively. A
      random-effects model and fixed-effect model were used to perform meta-analysis
      with and without heterogeneity, respectively. MAIN RESULTS: Nine RCTs (600
      patients) with seven comparing Shengmai plus usual treatment with usual treatment
      alone and three comparing Shengmai with placebo (one RCT contained three arms)
      were included in this updated review. Based upon the seven RCTs (494 patients),
      improvement of the New York Heart Association (NYHA) functional classification
      was more common in patients taking Shengmai plus usual treatment than in those
      receiving usual treatment alone (risk ratio 0.33, 95% confidence interval 0.23 to
      0.47). Beneficial effects of Shengmai in treating heart failure were also
      observed on other outcomes, including an exercise test, ejection fraction,
      cardiac output, cardiac index and left ventricular end-systolic volume. The three
      RCTs (106 patients) which compared Shengmai with placebo reported an improvement
      in NYHA functional classification, ejection fraction, stroke volume, cardiac
      index and myocardial contractility. Three out of the nine RCTs reported mild
      adverse effects, and two patients were withdrawn due to the adverse effects. The
      results of this review should be interpreted with caution. This is due to the
      studies being of low quality, their small sample size, and the significant
      heterogeneity for certain outcomes including ejection fraction and cardiac
      output. AUTHORS' CONCLUSIONS: Shengmai may be beneficial in treating heart
      failure, especially in terms of improving the NYHA functional classification with
      Shengmai plus usual treatment. However, the evidence for its effects on mortality
      and hospitalisation are not available yet. Therefore more studies, of higher
      quality and long-term follow-up, are needed to provide more evidence for the
      future use of Shengmai.

PMID- 23152230
TI  - Push versus gravity for intermittent bolus gavage tube feeding of premature and
      low birth weight infants.
AB  - BACKGROUND: Many small, sick and premature infants are unable to coordinate
      sucking, swallowing and breathing, and therefore, require gavage feeding. In
      gavage feeding, milk feeds are delivered through a tube passed via the nose or
      mouth into the stomach. Intermittent bolus milk feeds may be administered using a
      syringe to gently push milk into the infant's stomach (push feed). Alternatively,
      milk can be poured into a syringe attached to the tube and allowed to drip in by
      gravity (gravity feed). OBJECTIVES: To determine whether the use of push compared
      with gravity gavage feeding results in a more rapid establishment of full gavage
      feeds without increasing adverse events in preterm or low birth weight, infants
      who require intermittent bolus gavage feeding. SEARCH METHODS: We searched the
      following electronic databases to locate randomised controlled or quasi
      randomised trials: Cochrane Central Register of Controlled Trials (CENTRAL, The
      Cochrane Library, 2012, Issue 5), MEDLINE (from 1966 to May 2012), EMBASE (from
      1980 to May 2012), and CINAHL (from 1982 to May 2012). We used the standard
      search strategy of the Cochrane Neonatal Review Group. SELECTION CRITERIA:
      Randomised or quasi-randomised controlled trials comparing push versus gravity
      intermittent gavage tube feeding in premature or low birth weight, or both,
      infants. DATA COLLECTION AND ANALYSIS: We assessed the methodology of trials
      regarding blinding of randomisation and outcome measurement. We evaluated
      treatment effect with a fixed-effect model using risk ratio (RR), relative risk
      reduction, risk difference (RD) and number needed to treat (NNT) for categorical
      data; and using mean, standard deviation and weighted mean difference (WMD) for
      continuous data. We analysed outcomes measured as count data, for example
      frequency of apnoea, bradycardia and episodes of pulse oximeter oxygen (SpO(2))
      desaturation, by comparing rates of events and the rate ratio. We evaluated
      heterogeneity to help determine the suitability of pooling results. MAIN RESULTS:
      Only one small cross-over trial met the criteria for inclusion in this review and
      therefore meta-analysis for any of the treatment outcomes was not performed.
      Symon 1994 reported a trend towards a higher respiratory rate at 10 to 30 minutes
      following push gavage feeding and no statistical difference in the time taken to
      give the feeds regardless of the method used. AUTHORS' CONCLUSIONS: There was one
      small cross-over study that was included in this review. There is insufficient
      evidence to recommend either method of gavage feeding. A randomised trial is
      needed to evaluate the benefits and harms of push versus gravity bolus tube
      feeding in preterm infants. Infants should be stratified by gestational age at
      birth (above and below 32 weeks) or birth weight (above and below 1500 grams) and
      respiratory support (ventilated versus non-ventilated) and the sample size should
      be of sufficient size to evaluate the primary outcomes outlined in this review
      (time to establish full tube feeds and feeding intolerance).

PMID- 23152231
TI  - Adenosine-diphosphate (ADP) receptor antagonists for the prevention of
      cardiovascular disease in type 2 diabetes mellitus.
AB  - BACKGROUND: Cardiovascular disease (CVD) is the most prevalent complication of
      type 2 diabetes with an estimated 65% of people with type 2 diabetes dying from a
      cause related to atherosclerosis. Adenosine-diphosphate (ADP) receptor
      antagonists like clopidogrel, ticlopidine, prasugrel and ticagrelor impair
      platelet aggregation and fibrinogen-mediated platelet cross-linking and may be
      effective in preventing CVD. OBJECTIVES: To assess the effects of adenosine
      diphosphate (ADP) receptor antagonists for the prevention of cardiovascular
      disease in type 2 diabetes mellitus. SEARCH METHODS: We searched the Cochrane
      Central Register of Controlled Trials (CENTRAL) in The Cochrane Library (issue 2,
      2011), MEDLINE (until April 2011) and EMBASE (until May 2011). We also performed
      a manual search, checking references of original articles and pertinent reviews
      to identify additional studies. SELECTION CRITERIA: Randomised controlled trials
      comparing an ADP receptor antagonist with another antiplatelet agent or placebo
      for a minimum of 12 months in patients with diabetes. In particular, we looked
      for trials assessing clinical cardiovascular outcomes. DATA COLLECTION AND
      ANALYSIS: Two review authors extracted data for studies which fulfilled the
      inclusion criteria, using standard data extraction templates. We sought
      additional unpublished information and data from the principal investigators of
      all included studies. MAIN RESULTS: Eight studies with a total of 21,379 patients
      with diabetes were included. Three included studies investigated ticlopidine
      compared to aspirin or placebo. Five included studies investigated clopidogrel
      compared to aspirin or a combination of aspirin and dipyridamole, or compared
      clopidogrel in combination with aspirin to aspirin alone. All trials included
      patients with previous CVD except the CHARISMA trial which included patients with
      multiple risk factors for coronary artery disease. Overall the risk of bias of
      the trials was low. The mean duration of follow-up ranged from 365 days to 913
      days.Data for diabetes patients on all-cause mortality, vascular mortality and
      myocardial infarction were only available for one trial (355 patients). This
      trial compared ticlopidine to placebo and did not demonstrate any statistically
      significant differences for all-cause mortality, vascular mortality or myocardial
      infarction. Diabetes outcome data for stroke were available in three trials (31%
      of total diabetes participants). Overall pooling of two (statistically
      heterogeneous) studies showed no statistically significant reduction in the
      combination of fatal and non-fatal stroke (359/3194 (11.2%) versus 356/3146
      (11.3%), random effects odds ratio (OR) 0.81; 95% confidence interval (CI) 0.44
      to 1.49) for ADP receptor antagonists versus other antiplatelet drugs. There were
      no data available from any of the trials on peripheral vascular disease, health
      related quality of life, adverse events specifically for patients with diabetes,
      or costs. AUTHORS' CONCLUSIONS: The available evidence for ADP receptor
      antagonists in patients with diabetes mellitus is limited and most trials do not
      report outcomes for patients with diabetes separately. Therefore, recommendations
      for the use of ADP receptor antagonists for the prevention of CVD in patients
      with diabetes are based on available evidence from trials including patients with
      and without diabetes. Trials with diabetes patients and subgroup analyses of
      patients with diabetes in trials with combined populations are needed to provide
      a more robust evidence base to guide clinical management in patients with
      diabetes.

PMID- 23152232
TI  - Rehabilitation for ankle fractures in adults.
AB  - BACKGROUND: Rehabilitation after ankle fracture can begin soon after the fracture
      has been treated, either surgically or non-surgically, by the use of different
      types of immobilisation that allow early commencement of weight-bearing or
      exercise. Alternatively, rehabilitation, including the use of physical or manual
      therapies, may start following the period of immobilisation. This is an update of
      a Cochrane review first published in 2008. OBJECTIVES: To assess the effects of
      rehabilitation interventions following conservative or surgical treatment of
      ankle fractures in adults. SEARCH METHODS: We searched the Specialised Registers
      of the Cochrane Bone, Joint and Muscle Trauma Group and the Cochrane
      Rehabilitation and Related Therapies Field, CENTRAL via The Cochrane Library
      (2011 Issue 7), MEDLINE via PubMed, EMBASE, CINAHL, PEDro, AMED, SPORTDiscus and
      clinical trials registers up to July 2011. In addition, we searched reference
      lists of included studies and relevant systematic reviews. SELECTION CRITERIA:
      Randomised and quasi-randomised controlled trials with adults undergoing any
      interventions for rehabilitation after ankle fracture were considered. The
      primary outcome was activity limitation. Secondary outcomes included quality of
      life, patient satisfaction, impairments and adverse events. DATA COLLECTION AND
      ANALYSIS: Two review authors independently screened search results, assessed risk
      of bias and extracted data. Risk ratios and 95% confidence intervals (95% CIs)
      were calculated for dichotomous variables, and mean differences or standardised
      mean differences and 95% CIs were calculated for continuous variables. End of
      treatment and end of follow-up data were presented separately. For end of follow
      up data, short term follow-up was defined as up to three months after
      randomisation, and long-term follow-up as greater than six months after
      randomisation. Meta-analysis was performed where appropriate. MAIN RESULTS:
      Thirty-eight studies with a total of 1896 participants were included. Only one
      study was judged at low risk of bias. Eight studies were judged at high risk of
      selection bias because of lack of allocation concealment and over half the of the
      studies were at high risk of selective reporting bias.Three small studies
      investigated rehabilitation interventions during the immobilisation period after
      conservative orthopaedic management. There was limited evidence from two studies
      (106 participants in total) of short-term benefit of using an air-stirrup versus
      an orthosis or a walking cast. One study (12 participants) found 12 weeks of
      hypnosis did not reduce activity or improve other outcomes.Thirty studies
      investigated rehabilitation interventions during the immobilisation period after
      surgical fixation. In 10 studies, the use of a removable type of immobilisation
      combined with exercise was compared with cast immobilisation alone. Using a
      removable type of immobilisation to enable controlled exercise significantly
      reduced activity limitation in five of the eight studies reporting this outcome,
      reduced pain (number of participants with pain at the long term follow-up: 10/35
      versus 25/34; risk ratio (RR) 0.39, 95% confidence interval (CI) 0.22 to 0.68; 2
      studies) and improved ankle dorsiflexion range of motion. However, it also led to
      a higher rate of mainly minor adverse events (49/201 versus 20/197; RR 2.30, 95%
      CI 1.49 to 3.56; 7 studies).During the immobilisation period after surgical
      fixation, commencing weight-bearing made a small improvement in ankle
      dorsiflexion range of motion (mean difference in the difference in range of
      motion compared with the non-fractured side at the long term follow-up 6.17%, 95%
      CI 0.14 to 12.20; 2 studies). Evidence from one small but potentially biased
      study (60 participants) showed that neurostimulation, an electrotherapy modality,
      may be beneficial in the short-term. There was little and inconclusive evidence
      on what type of support or immobilisation was the best. One study found no
      immobilisation improved ankle dorsiflexion and plantarflexion range of motion
      compared with cast immobilisation, but another showed using a backslab improved
      ankle dorsiflexion range of motion compared with using a bandage.Five studies
      investigated different rehabilitation interventions following the immobilisation
      period after either conservative or surgical orthopaedic management. There was no
      evidence of effect for stretching or manual therapy in addition to exercise, or
      exercise compared with usual care. One small study (14 participants) at a high
      risk of bias found reduced ankle swelling after non-thermal compared with thermal
      pulsed shortwave diathermy. AUTHORS' CONCLUSIONS: There is limited evidence
      supporting early commencement of weight-bearing and the use of a removable type
      of immobilisation to allow exercise during the immobilisation period after
      surgical fixation. Because of the potential increased risk of adverse events, the
      patient's ability to comply with the use of a removable type of immobilisation to
      enable controlled exercise is essential. There is little evidence for
      rehabilitation interventions during the immobilisation period after conservative
      orthopaedic management and no evidence for stretching, manual therapy or exercise
      compared to usual care following the immobilisation period. Small, single studies
      showed that some electrotherapy modalities may be beneficial. More clinical
      trials that are well-designed and adequately-powered are required to strengthen
      current evidence.

PMID- 23152233
TI  - Exercise for the management of cancer-related fatigue in adults.
AB  - BACKGROUND: Cancer-related fatigue is recognised as an important symptom
      associated with cancer and its treatment. A number of studies have investigated
      the effects of physical activity in reducing cancer-related fatigue. This is an
      updated version of the original Cochrane review published in The Cochrane Library
      (2008, Issue 1). The original review identified some benefits of physical
      activity on fatigue in cancer both during and after adjuvant treatment. We
      identified a number of limitations in the evidence, providing clear justification
      for an updated review. OBJECTIVES: To evaluate the effect of exercise on cancer
      related fatigue both during and after cancer treatment. SEARCH METHODS: We
      searched the Cochrane Central Register of Controlled Trials (CENTRAL) (Issue 1,
      2011), MEDLINE (1966 to March 2011), EMBASE (1980 to March 2011), CINAHL (1982 to
      March 2011), British Nursing Index (January 1984 to March 2011), AMED (1985 to
      March 2011), SIGLE (1980 to March 2011) and Dissertation Abstracts International
      (1861 to March 2011) using key words. We also searched reference lists off all
      studies identified for inclusion and relevant reviews. In addition, we
      handsearched relevant journals and contacted experts in the field of cancer
      related fatigue. SELECTION CRITERIA: We sought and included randomised controlled
      trials (RCTs) that investigated the effect of exercise on cancer-related fatigue
      in adults. DATA COLLECTION AND ANALYSIS: Two review authors independently
      assessed the risk of bias of studies and extracted data based upon predefined
      criteria. Where data were available we performed meta-analyses for fatigue using
      a random-effects model. MAIN RESULTS: For this update we identified a total of 56
      studies (4068 participants) for inclusion (28 from the original search and 28
      from the updated search), with the majority carried out in participants with
      breast cancer (28 studies). A meta-analysis of all fatigue data, incorporating 38
      comparisons, provided data for 1461 participants who received an exercise
      intervention and 1187 control participants. At the end of the intervention period
      exercise was seen to be statistically more effective than the control
      intervention (standardised mean difference (SMD) -0.27, 95% confidence interval
      (CI) -0.37 to -0.17). Benefits of exercise on fatigue were observed for
      interventions delivered during or post-adjuvant cancer therapy. In relation to
      diagnosis, we identified benefits of exercise on fatigue for breast and prostate
      cancer but not for those with haematological malignancies. Finally, aerobic
      exercise significantly reduced fatigue but resistance training and alternative
      forms of exercise failed to reach significance. AUTHORS' CONCLUSIONS: The
      findings of the updated review have enabled a more precise conclusion to be made
      in that aerobic exercise can be regarded as beneficial for individuals with
      cancer-related fatigue during and post-cancer therapy, specifically those with
      solid tumours. Further research is required to determine the optimal type,
      intensity and timing of an exercise intervention.

PMID- 23152234
TI  - Sedation versus general anaesthesia for provision of dental treatment in under 18
      year olds.
AB  - BACKGROUND: A significant proportion of children have caries requiring
      restorations or extractions, and some of these children will not accept this
      treatment under local anaesthetic. Historically this has been managed in children
      by the use of a general anaesthetic, however use of sedation may lead to reduced
      morbidity and cost. The aim of this review is to compare the efficiency of
      sedation versus general anaesthesia for the provision of dental treatment for
      children and adolescents aged under 18 years.This review was originally published
      in 2009 and updated in 2012. OBJECTIVES: We evaluated the intra- and
      postoperative morbidity, effectiveness and cost effectiveness of sedation versus
      general anaesthesia for the provision of dental treatment for under 18 year olds.
      SEARCH METHODS: In this updated review we searched the Cochrane Central Register
      of Controlled Trials (CENTRAL) (The Cochrane Library 2012, Issue 7); MEDLINE
      (Ovid) (1950 to July 2012); EMBASE (Ovid) (1974 to July 2012); System for
      information on Grey Literature in Europe (SIGLE) (1980 to October 2008), Latin
      American & Caribbean Health Sciences Literature (LILACS) (1982 to July 2012), and
      ISI Web of Science (1945 to October 2008). The searches were updated to July
      2012. The original search was performed in October 2008.We also carried out
      handsearching of relevant journals to July 2012. We imposed no language
      restriction. SELECTION CRITERIA: We planned to include randomized controlled
      clinical trials of sedative agents compared to general anaesthesia in children
      and adolescents aged up to 18 years having dental treatment. We excluded complex
      surgical procedures and pseudo-randomized trials. DATA COLLECTION AND ANALYSIS:
      Two authors assessed titles and abstracts for inclusion in the review. We
      recorded information relevant to the objectives and outcome measures in a
      specially designed 'data extraction form'. MAIN RESULTS: We identified 15 studies
      for potential inclusion after searching the available databases and screening the
      titles and abstracts. We identified a further study through personal contacts.
      Following full text retrieval of the studies, we found none to be eligible for
      inclusion in this review. AUTHORS' CONCLUSIONS: Randomized controlled studies are
      required comparing the use of dental general anaesthesia with sedation to
      quantify differences such as morbidity and cost.

PMID- 23152235
TI  - Sound therapy (masking) in the management of tinnitus in adults.
AB  - BACKGROUND: This is an update of a Cochrane Review first published in The
      Cochrane Library in Issue 12, 2010.Tinnitus is described as the perception of
      sound or noise in the absence of real acoustic stimulation. Numerous management
      strategies have been tried for this potentially debilitating, heterogeneous
      symptom. External noise has been used as a management tool for tinnitus, in
      different capacities and with different philosophical intent, for over a century.
      OBJECTIVES: To assess the effectiveness of sound-creating devices (including
      hearing aids) in the management of tinnitus in adults. Primary outcome measures
      were changes in the loudness or severity of tinnitus and/or impact on quality of
      life. Secondary outcome measures were change in pure-tone auditory thresholds and
      adverse effects of treatment.  SEARCH METHODS: We searched the Cochrane ENT Group
      Trials Register; 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 8
      February 2012. SELECTION CRITERIA: Prospective randomised controlled trials
      recruiting adults with persistent, distressing, subjective tinnitus of any
      aetiology in which the management strategy included maskers, noise-generating
      device and/or hearing aids, used either as the sole management tool or in
      combination with other strategies, including counselling. DATA COLLECTION AND
      ANALYSIS: Two authors independently examined the 387 search results to identify
      studies for inclusion in the review, of which 33 were potentially relevant. The
      update searches in 2012 retrieved no further potentially relevant studies. Both
      authors extracted data independently. MAIN RESULTS: Six trials (553 participants)
      are included in this review. Studies were varied in design, with significant
      heterogeneity in the evaluation of subjective tinnitus perception, with different
      scores, scales, tests and questionnaires as well as variance in the outcome
      measures used to assess the improvement in tinnitus sensation/quality of life.
      This precluded meta-analysis of the data. There was no long-term follow-up. We
      assessed the risk of bias as medium in three and high in three studies. Following
      analysis of the data, no significant change was seen in the loudness of tinnitus
      or the overall severity of tinnitus following the use of sound therapy compared
      to other interventions such as patient education, 'relaxation techniques',
      'tinnitus coping strategies', counselling, 'tinnitus retraining' and exposure to
      environmental sounds. No side effects or significant morbidity were reported from
      the use of sound-creating devices. AUTHORS' CONCLUSIONS: The limited data from
      the included studies failed to show strong evidence of the efficacy of sound
      therapy in tinnitus management. The absence of conclusive evidence should not be
      interpreted as evidence of lack of effectiveness. The lack of quality research in
      this area, in addition to the common use of combined approaches (hearing therapy
      plus counselling) in the management of tinnitus are, in part, responsible for the
      lack of conclusive evidence. Other combined forms of management, such as tinnitus
      retraining therapy, have been subject to a Cochrane Review. Optimal management
      may involve multiple strategies.

PMID- 23152236
TI  - Benzodiazepines for schizophrenia.
AB  - BACKGROUND: Because of the high number of people with schizophrenia not
      responding adequately to monotherapy with antipsychotic agents, the evidence
      regarding the efficacy and safety of additional medication was examined in a
      number of clinical trials. One approach to this research question was the use of
      benzodiazepines, as monotherapy as well as in combination with antipsychotics.
      OBJECTIVES: To determine the efficacy, acceptability, and tolerability of
      benzodiazepines in people with schizophrenia and schizophrenia-like psychoses.
      SEARCH METHODS: In February 2011, we updated the literature search of the
      previous version of this systematic review (last search March 2005). We searched
      the trial register of the Cochrane Schizophrenia Group (containing methodical
      searches of BIOSIS, CINAHL, Dissertation abstracts, EMBASE, LILACS, MEDLINE,
      PSYNDEX, PsycINFO, RUSSMED, Sociofile, supplemented with hand searching of
      relevant journals and numerous conference proceedings). Additionally, we
      inspected references of all identified studies for further relevant studies and
      contacted authors of relevant publications in order to obtain missing data from
      existing trials. We applied no language restrictions. SELECTION CRITERIA: We
      included all randomised controlled trials comparing benzodiazepines (as
      monotherapy or as adjunctive agent) with antipsychotic drugs or placebo for the
      pharmacological management of schizophrenia and/or schizophrenia-like psychoses.
      DATA COLLECTION AND ANALYSIS: Review authors (MD and CL) analysed independently
      the new references of the update-search referring to the inclusion criteria. MD
      and CL extracted all data from the included trials. For dichotomous outcomes we
      calculated risk ratios (RR) and their 95% confidence intervals (CI). We analysed
      continuous data by using mean differences (MD) and their 95% CI. We assessed each
      pre-selected outcome from the included trials with the risk of bias tool. MAIN
      RESULTS: The 2011 update search yielded three further randomised controlled
      trials. The review currently includes 34 studies with 2657 participants. Most
      studies were characterised by a small sample size, short duration, and incomplete
      outcome data reporting.Benzodiazepine monotherapy is compared with placebo in
      eight trials. The proportion of participants with no clinically important
      response did not significantly differ between those given benzodiazepines or
      placebo (N = 382, 6 RCTs, RR 0.67 CI 0.44 to 1.02). The results from the various
      rating scales applied to assess global and mental state were
      inconsistent.Fourteen studies examined benzodiazepine monotherapy in comparison
      with antipsychotic monotherapy. Clinically important treatment response
      assessment revealed no statistically significant difference between the study
      groups (30 minutes: N = 44, 1 RCT, RR 0.91 CI 0.58 to 1.43; 60 minutes: N = 44,1
      RCT, RR 0.61 CI 0.20 to 1.86; 12 hours: N = 66, 1 RCT, RR 0.75 CI 0.44 to 1.30;
      pooled short-term studies: N = 112, 2 RCTs, RR 1.48 CI 0.64 to 3.46). Desired
      sedation occurred significantly more often among participants in the
      benzodiazepine group than in the antipsychotic group at 20 and 40 minutes. No
      significant between-group differences could be identified for global and mental
      state or occurrence of adverse effects.Twenty trials compared benzodiazepine
      augmentation of antipsychotics with antipsychotic monotherapy. Referring to
      clinically important response, statistically significant improvement could be
      demonstrated only for the first 30 minutes of augmentation treatment (30 minutes:
      1 RCT, N = 45, RR 0.38 CI 0.18 to 0.80; 60 minutes: N = 45,1 RCT, RR 0.07 CI 0.00
      to 1.13; 12 hour: N = 67,1 RCT, RR 0.85 CI 0.51 to 1.41; pooled short-term
      studies: N = 511, 6 RCTs, RR 0.87 CI 0.49 to 1.54). Analyses of the global and
      mental state yielded no between-group differences except for desired sedation at
      30 as well as 60 minutes (30 minutes: N = 45, 1 RCT, RR 2.25 CI 1.18 to 4.30; 60
      minutes: N = 45, 1 RCT, RR 1.39 CI 1.06 to 1.83). AUTHORS' CONCLUSIONS: There is
      currently no convincing evidence to confirm or refute the practise of
      administering benzodiazepines as monotherapy or in combination with
      antipsychotics for the pharmacological treatment of schizophrenia and
      schizophrenia-like psychosis. Low-quality evidence suggests that benzodiazepines
      are effective for very short-term sedation and could be considered for calming
      acutely agitated people with schizophrenia. Measured by the overall attrition
      rate, the acceptability of benzodiazepine treatment appears to be adequate.
      Adverse effects were generally poorly reported. High-quality future research
      projects with large sample sizes are required to clarify the evidence of
      benzodiazepine treatment in schizophrenia, especially regarding long-term
      augmentation strategies.

PMID- 23152237
TI  - Endovascular versus conventional medical treatment for uncomplicated chronic type
      B aortic dissection.
AB  - BACKGROUND: Aortic dissection is a potentially life-threatening condition that
      occurs when a tear forms in the inner lining of the aorta. It has traditionally
      been treated by blood pressure control (medical treatment) or open surgery, both
      with high mortality rates. More recently stent-graft repair has been suggested as
      an alternative. OBJECTIVES: To identify the best management for uncomplicated
      (without rupture of the organs or malperfusion of the extremities) subacute or
      chronic type B aortic dissection. SEARCH METHODS: The Cochrane Peripheral
      Vascular Diseases Group Trials Search Co-ordinator searched their Specialised
      Register (last searched May 2012) and CENTRAL (2012, Issue 4). Clinical trials
      databases were searched for ongoing or unpublished studies. SELECTION CRITERIA:
      All randomised controlled trials designed to compare the outcome of uncomplicated
      (without rupture of the organs or malperfusion of the extremities) chronic
      (occurring more than two weeks previously) type B aortic dissection when treated
      by stenting adjunctive to best medical treatment versus best medical treatment
      alone were included. DATA COLLECTION AND ANALYSIS: Data on all cause and aorta
      related mortality at two years was collected and analysed. In addition, secondary
      outcome measures were analysed, including morbidity, complications (additional
      endovascular or open surgery for rupture, expansion or malperfusion) and quality
      of life. MAIN RESULTS: A single trial was identified that fulfilled the inclusion
      criteria (INSTEAD trial). The two-year all cause survival was not statistically
      significantly different between study groups (95.6% +/- 2.5% in the optimised
      medical therapy (OMT) group and 88.9% +/- 3.7% in the thoracic endovascular
      aneurysm repair (TEVAR) + OMT group; log rank test P = 0.15). AUTHORS'
      CONCLUSIONS: Overall, the data at two years were insufficient to make any
      practice recommendations. However, the data on the anatomic remodeling of
      dissected aortas observed after TEVAR + OMT is encouraging and future studies
      should follow up cases for at least five years to see if early endovascular
      interventions, even in stable initially uncomplicated type B patients, are of
      long-term benefit.

PMID- 23152238
TI  - Mobile phone-based interventions for smoking cessation.
AB  - BACKGROUND: Innovative and effective smoking cessation interventions are required
      to appeal to those who are not accessing traditional cessation services. Mobile
      phones are widely used and are now well-integrated into the daily lives of many,
      particularly young adults. Mobile phones are a potential medium for the delivery
      of health programmes such as smoking cessation. OBJECTIVES: To determine whether
      mobile phone-based interventions are effective at helping people who smoke, to
      quit. SEARCH METHODS: For the most recent update, we searched the Cochrane
      Tobacco Addiction Group Specialised Register in May 2012. We also searched UK
      Clinical Research Network Portfolio for current projects in the UK and the
      ClinicalTrials register for on-going or recently completed studies. We searched
      through the reference lists of identified studies and attempted to contact the
      authors of ongoing studies, with no restrictions placed on language or
      publication date. SELECTION CRITERIA: We included randomized or quasi-randomized
      trials. Participants were smokers of any age who wanted to quit. Studies were
      those examining any type of mobile phone-based intervention. This included any
      intervention aimed at mobile phone users, based around delivery via mobile phone,
      and using any functions or applications that can be used or sent via a mobile
      phone. DATA COLLECTION AND ANALYSIS: Information on risk of bias and
      methodological details was extracted using a standardised form. Participants who
      dropped out of the trials or were lost to follow-up were considered to be
      smoking. We calculated risk ratios (RR) for each included study. Meta-analysis of
      the included studies was undertaken using the Mantel-Haenszel fixed-effect
      method. Where meta-analysis was not possible, summary and descriptive statistics
      are presented. MAIN RESULTS: Five studies with at least six month cessation
      outcomes were included in this review. Three studies involve a purely text
      messaging intervention that has been adapted over the course of these three
      studies for different populations and contexts. One study is a multi-arm study of
      a text messaging intervention and an internet QuitCoach separately and in
      combination. The final study involves a video messaging intervention delivered
      via the mobile phone. When all five studies were pooled, mobile phone
      interventions were shown to increase the long term quit rates compared with
      control programmes (RR 1.71, 95% CI 1.47 to 1.99, over 9000 participants), using
      a definition of abstinence of no smoking at six months since quit day but
      allowing up to three lapses or up to five cigarettes. Statistical heterogeneity
      was substantial as indicated by the I2 statistic (I2 = 79%), but as all included
      studies were similar in design, intervention and primary outcome measure, we have
      presented the meta-analysis in this review. AUTHORS' CONCLUSIONS: The current
      evidence shows a benefit of mobile phone-based smoking cessation interventions on
      long-term outcomes, though results were heterogenous with findings from three of
      five included studies crossing the line of no effect. The studies included were
      predominantly of text messaging interventions. More research is required into
      other forms of mobile phone-based interventions for smoking cessation, other
      contexts such as low income countries, and cost-effectiveness.

PMID- 23152239
TI  - Locomotor training for walking after spinal cord injury.
AB  - BACKGROUND: A traumatic spinal cord injury (SCI) is a lesion of neural elements
      of the spinal cord that can result in any degree of sensory and motor deficit,
      autonomic or bowel dysfunction. Improvement of locomotor function is one of the
      primary goals for people with SCI. Locomotor training for walking is therefore
      used in rehabilitation after SCI and might help to improve a person's ability to
      walk. However, a systematic review of the evidence is required to assess the
      effects and acceptability of locomotor training after SCI. OBJECTIVES: To assess
      the effects of locomotor training on improvement in walking for people with
      traumatic SCI. SEARCH METHODS: We searched the Cochrane Injuries Group's
      Specialised Register (searched November 2011); the Cochrane Central Register of
      Controlled Trials (CENTRAL) (The Cochrane Library 2011, Issue 4); MEDLINE (Ovid)
      (1966 to November 2011); EMBASE (Ovid) (1980 to November 2011); CINAHL (1982 to
      November 2011); AMED (Allied and Complementary Medicine Database) (1985 to
      November 2011); SPORTDiscus (1949 to November 2011); PEDro (the Physiotherapy
      Evidence database) (searched November 2011); COMPENDEX (engineering databases)
      (1972 to November 2011); and INSPEC (1969 to November 2011). We also searched the
      online trials databases Current Controlled Trials (www.controlled
      trials.com/isrctn) and Clinical Trials (www.clinicaltrials.gov). We handsearched
      relevant conference proceedings, checked reference lists of relevant published
      papers and contacted study authors in an effort to identify published,
      unpublished and ongoing trials. SELECTION CRITERIA: We included randomised
      controlled trials (RCTs) involving people with SCI that compared locomotor
      training to a control of any other exercise or no treatment. DATA COLLECTION AND
      ANALYSIS: Two review authors independently selected trials for inclusion,
      assessed trial quality and extracted data. The primary outcomes were the speed of
      walking and walking capacity at final follow-up. MAIN RESULTS: Five RCTs
      involving 309 people are included in this review. Overall, the results were
      inconclusive. There was no statistically significant superior effect of any
      locomotor training approach on walking function after SCI compared with any other
      kind of physical rehabilitation. The use of bodyweight supported treadmill
      training as locomotor training for people after SCI did not significantly
      increase walking velocity (0.03 m/sec with a 95% confidence interval (CI) -0.05
      to 0.11; P = 0.52; I(2) = 22%) nor did it increase walking capacity (-1.3 metres
      (95% CI -41 to 40); P = 0.95; I(2) = 62%). However, in one study involving 74
      people the group receiving robotic-assisted locomotor training had reduced
      walking capacity compared with people receiving any other intervention, a finding
      which needs further investigation. In all five studies there were no differences
      in adverse events or drop-outs between study groups. AUTHORS' CONCLUSIONS: There
      is insufficient evidence from RCTs to conclude that any one locomotor training
      strategy improves walking function more than another for people with SCI. The
      effects especially of robotic-assisted locomotor training are not clear,
      therefore research in the form of large RCTs, particularly for robotic training,
      is needed. Specific questions about which type of locomotor training might be
      most effective in improving walking function for people with SCI need to be
      explored.

PMID- 23152240
TI  - Continuation and maintenance treatments for depression in older people.
AB  - BACKGROUND: Depressive illness in older people causes significant suffering and
      health service utilisation. Relapse and recurrence rates are high. OBJECTIVES: To
      examine the efficacy of antidepressants and psychological therapies in preventing
      the relapse and recurrence of depression in older people. SEARCH METHODS: Search
      of the Cochrane Depression, Anxiety and Neurosis Review Group's specialized
      register (the CCDANCTR) up to 22 June 2012. The CCDANCTR includes relevant
      randomised controlled trials from the following bibliographic databases: The
      Cochrane Library (all years), EMBASE, (1974 to date) MEDLINE (1950 to date) and
      PsycINFO (1967 to date). We handsearched relevant journals, contacted experts in
      the field and examined reference lists, conference proceedings and
      bibliographies. SELECTION CRITERIA: Both review authors independently selected
      studies. We included randomised controlled trials (RCTs) involving people aged 60
      and over successfully treated for an episode of depression and randomised to
      receive continuation and maintenance treatment with antidepressants,
      psychological therapies, or combination. DATA COLLECTION AND ANALYSIS: Data were
      extracted independently by the two authors.The primary outcome was
      relapse/recurrence rate of depression (reaching a cut-off on any depression
      rating scale) at six-monthly intervals. Secondary outcomes included global
      impression of change, social functioning, and deaths. Meta-analysis was performed
      using risk ratio for dichotomous outcomes and mean differences (MD) for
      continuous outcomes, with 95% confidence intervals. MAIN RESULTS: Seven studies
      met the inclusion criteria (803 participants). Six compared antidepressant
      medication with placebo; two involved psychological therapies. There was marked
      heterogeneity between the studies.Comparing antidepressants with placebo, at six
      months follow-up there was no significant difference. At 12 months follow-up
      there was a statistically significant difference favouring antidepressants in
      reducing recurrence compared with placebo (three RCTs, N = 247, RR = 0.67, 95% CI
      0.55 to 0.82; NNTB = five). At 24 months there was no significant difference for
      antidepressants overall, however, for the subgroup of tricyclic antidepressants
      there was significant benefit (three RCTs, N = 169, RR = 0.70, 95% CI 0.50 to
      0.99; NNTB = five). At 36 months there was no significant difference for
      antidepressants overall. There was no difference in treatment acceptability or
      death rates between antidepressant and placebo.There was no significant
      difference between psychological treatment and antidepressant in recurrence rates
      at 12, 24, and 36 months (one RCT, N = 53) or between combination and
      antidepressant alone.Overall, the included studies were at low risk of bias.
      AUTHORS' CONCLUSIONS: The long-term benefits of continuing antidepressant
      medication in the prevention of recurrence of depression in older people are not
      clear and no firm treatment recommendations can be made on the basis of this
      review. Continuing antidepressant medication for 12 months appears to be helpful
      but this is based on only three small studies with relatively few participants
      using differing classes of antidepressants in clinically heterogeneous
      populations. Comparisons at other time points did not reach statistical
      significance. Data on psychological therapies and combined treatments are too
      limited to draw any conclusions.

PMID- 23152241
TI  - Psychosocial interventions to improve quality of life and emotional wellbeing for
      recently diagnosed cancer patients.
AB  - BACKGROUND: A cancer diagnosis may lead to significant psychological distress in
      up to 75% of cases. There is a lack of clarity about the most effective ways to
      address this psychological distress. OBJECTIVES: To assess the effects of
      psychosocial interventions to improve quality of life (QoL) and general
      psychological distress in the 12-month phase following an initial cancer
      diagnosis. SEARCH METHODS: We searched the Cochrane Central Register of
      Controlled Trials (CENTRAL) (The Cochrane Library 2010, Issue 4), MEDLINE,
      EMBASE, and PsycINFO up to January 2011. We also searched registers of clinical
      trials, abstracts of scientific meetings and reference lists of included studies.
      Electronic searches were carried out across all primary sources of peer-reviewed
      publications using detailed criteria. No language restrictions were imposed.
      SELECTION CRITERIA: Randomised controlled trials of psychosocial interventions
      involving interpersonal dialogue between a 'trained helper' and individual newly
      diagnosed cancer patients were selected. Only trials measuring QoL and general
      psychological distress were included. Trials involving a combination of
      pharmacological therapy and interpersonal dialogue were excluded, as were trials
      involving couples, family members or group formats. DATA COLLECTION AND ANALYSIS:
      Trial data were examined and selected by two authors in pairs with mediation from
      a third author where required. Where possible, outcome data were extracted for
      combining in a meta-analyses. Continuous outcomes were compared using
      standardised mean differences and 95% confidence intervals, using a random
      effects model. The primary outcome, QoL, was examined in subgroups by outcome
      measurement, cancer site, theoretical basis for intervention, mode of delivery
      and discipline of trained helper. The secondary outcome, general psychological
      distress (including anxiety and depression), was examined according to specified
      outcome measures. MAIN RESULTS: A total of 3309 records were identified, examined
      and the trials subjected to selection criteria; 30 trials were included in the
      review. No significant effects were observed for QoL at 6-month follow up (in 9
      studies, SMD 0.11; 95% CI -0.00 to 0.22); however, a small improvement in QoL was
      observed when QoL was measured using cancer-specific measures (in 6 studies, SMD
      0.16; 95% CI 0.02 to 0.30). General psychological distress as assessed by 'mood
      measures' improved also (in 8 studies, SMD - 0.81; 95% CI -1.44 to - 0.18), but
      no significant effect was observed when measures of depression or anxiety were
      used to assess distress (in 6 studies, depression SMD 0.12; 95% CI -0.07 to 0.31;
      in 4 studies, anxiety SMD 0.05; 95% CI -0.13 to 0.22). Psychoeducational and
      nurse-delivered interventions that were administered face to face and by
      telephone with breast cancer patients produced small positive significant effects
      on QoL (in 2 studies, SMD 0.23; 95% CI 0.04 to 0.43). AUTHORS' CONCLUSIONS: The
      significant variation that was observed across participants, mode of delivery,
      discipline of 'trained helper' and intervention content makes it difficult to
      arrive at a firm conclusion regarding the effectiveness of psychosocial
      interventions for cancer patients. It can be tentatively concluded that nurse
      delivered interventions comprising information combined with supportive attention
      may have a beneficial impact on mood in an undifferentiated population of newly
      diagnosed cancer patients.

PMID- 23152242
TI  - Doxycycline for osteoarthritis of the knee or hip.
AB  - BACKGROUND: Osteoarthritis is a chronic joint disease that involves degeneration
      of articular cartilage. Pre-clinical data suggest that doxycycline might act as a
      disease-modifying agent for the treatment of osteoarthritis, with the potential
      to slow cartilage degeneration. This is an update of a Cochrane review first
      published in 2009. OBJECTIVES: To examine the effects of doxycycline compared
      with placebo or no intervention on pain and function in people with
      osteoarthritis of the hip or knee. SEARCH METHODS: We searched CENTRAL (The
      Cochrane Library 2008, issue 3), MEDLINE, EMBASE and CINAHL up to 28 July 2008,
      with an update performed at 16 March 2012. In addition, we checked conference
      proceedings, reference lists, and contacted authors. SELECTION CRITERIA: We
      included studies if they were randomised or quasi-randomised controlled trials
      that compared doxycycline at any dosage and any formulation with placebo or no
      intervention in people with osteoarthritis of the knee or hip. DATA COLLECTION
      AND ANALYSIS: We extracted data in duplicate. We contacted investigators to
      obtain missing outcome information. We calculated differences in means at follow
      up between experimental and control groups for continuous outcomes and risk
      ratios (RR) for binary outcomes. MAIN RESULTS: We identified one additional trial
      (232 participants) and included two trials (663 participants) in this update. The
      methodological quality and the quality of reporting were considered moderate. At
      end of treatment, clinical outcomes were similar between the two treatment
      groups, with an effect size of -0.05 (95% confidence interval (CI) -0.22 to
      0.13), corresponding to a difference in pain scores between doxycycline and
      control of -0.1 cm (95% CI -0.6 to 0.3 cm) on a 10-cm visual analogue scale, or
      32% versus 29% improvement from baseline (difference 3%; 95% CI -5% to 10%). The
      effect size for function was -0.07 (95% CI -0.25 to 0.10), corresponding to a
      difference between doxycycline and control of -0.2 (95% CI -0.5 to 0.2) on the
      Western Ontario and McMaster Universities Arthritis Index (WOMAC) disability
      subscale with a range of 0 to 10, or 24% versus 21% improvement (difference 3%;
      95% CI -3% to 10%). The difference in changes in minimum joint space narrowing
      assessed in one trial was in favour of doxycycline (-0.15 mm; 95% CI -0.28 to 
      0.02 mm), which corresponds to a small effect size of -0.23 standard deviation
      units (95% CI -0.44 to -0.02). More participants withdrew from the doxycycline
      group compared with placebo due to adverse events (RR 2.28; 95% CI 1.06 to 4.90).
      There was no evidence that participants in the doxycycline group experienced more
      serious adverse events than those in the placebo group, but the estimate was
      imprecise (RR 1.07; 95% CI 0.68 to 1.68). AUTHORS' CONCLUSIONS: In this update,
      the strength of evidence for effectiveness outcomes was improved from low to
      moderate and we confirmed that the symptomatic benefit of doxycycline is minimal
      to non-existent, while the small benefit in terms of joint space narrowing is of
      questionable clinical relevance and outweighed by safety problems. The CIs of the
      summary estimates now exclude any clinically relevant difference in improvement
      of symptoms and the small benefit in terms of joint space narrowing does not
      outweigh the harms.

PMID- 23152243
TI  - Surgery versus radical endotherapies for early cancer and high-grade dysplasia in
      Barrett's oesophagus.
AB  - BACKGROUND: Barrett's oesophagus is one of the most common pre-malignant lesions
      in the world. Currently the mainstay of therapy is surgical management of
      advanced cancer but this has improved the five-year survival very little since
      the 1980s. As a consequence, improved survival relies on early detection through
      endoscopic surveillance programmes. Success of this strategy relies on the fact
      that late-stage pre-malignant lesions or very early cancers can be cured by
      intervention. Currently there is considerable controversy over which method is
      best: that is conventional open surgery or endotherapy (techniques involving
      endoscopy). OBJECTIVES: We used data from randomised controlled trials (RCTs) to
      examine the effectiveness of endotherapies compared with surgery in people with
      Barrett's oesophagus, those with early neoplasias (defined as high-grade
      dysplasia (HGD) and those with early cancer (defined as carcinoma in-situ,
      superficially invasive, early cancer or superficial cancer T-1m (T1-a) and T-1sm
      (T1-b)). SEARCH METHODS: We used the Cochrane highly sensitive search strategy to
      identify RCTs in MEDLINE, EMBASE, the Cochrane Central Register of Controlled
      Trials (CENTRAL), ISI Web of Science, EBMR, Controlled Trials mRCT and ISRCTN,
      and LILACS, in July and August 2008. The searches were updated in 2009 and again
      in April 2012. SELECTION CRITERIA: Types of studies: RCTs comparing endotherapies
      with surgery in the treatment of or early cancer. All cellular types of cancer
      were included (i.e. adenocarcinomas, squamous cell carcinomas and more unusual
      types) but will be discussed separately. TYPES OF PARTICIPANTS: patients of any
      age and either gender with a histologically confirmed diagnosis of early
      neoplasia (HGD and early cancer) in Barrett's or squamous lined oesophagus.Types
      of interventions; endotherapies (the intervention) compared with surgery (the
      control), all with curative intent. DATA COLLECTION AND ANALYSIS: Reports of
      studies that meet the inclusion criteria for this review would have been analysed
      using the methods detailed in Appendix 9. MAIN RESULTS: We did not identify any
      studies that met the inclusion criteria. In total we excluded 13 studies that
      were not RCTs but that compared surgery and endotherapies. AUTHORS' CONCLUSIONS:
      This Cochrane review has indicated that there are no RCTs to compare management
      options in this vital area, therefore trials should be undertaken as a matter of
      urgency. The problems with such randomised methods are standardising surgery and
      endotherapies in all sites, standardising histopathology in all centres,
      assessing which patients are fit or unfit for surgery and making sure there are
      relevant outcomes for the study (i.e. long-term survival (over five or more
      years)) and no progression of HGD.

PMID- 23152244
TI  - Surgical versus non-surgical management of abdominal injury.
AB  - BACKGROUND: Injury to the abdomen can be blunt or penetrating. Abdominal injury
      can damage internal organs such as the liver, spleen, kidneys, and intestine.
      There are controversies about the best approach to manage abdominal injuries.
      OBJECTIVES: To assess the effects of surgical and non-surgical interventions in
      the management of abdominal trauma. SEARCH METHODS: We searched the Cochrane
      Injuries Group's Specialised Register, CENTRAL (The Cochrane Library 2012, issue
      1), MEDLINE, PubMed, EMBASE, ISI Web of Science: Science Citation Index Expanded
      (SCI-EXPANDED), and ISI Web of Science: Conference Proceedings Citation Index
      Science (CPCI-S) all until January 2012; CINAHL until January 2009. We also
      searched the reference lists of all eligible studies and the trial registers
      www.controlled-trials.com and www.clinicaltrials.gov in January 2012. SELECTION
      CRITERIA: Randomised controlled trials of surgical and non surgical interventions
      among patients with abdominal injury who are haemodynamically stable and with no
      signs of peritonitis. DATA COLLECTION AND ANALYSIS: Two review authors
      independently applied the search criteria. One study involving participants with
      penetrating abdominal injury met the inclusion criteria. Data were extracted by
      two authors using a standard data extraction form. MAIN RESULTS: One study
      including 51 participants with moderate risk of bias was included. Participants
      were randomised to surgery or an observation protocol. There were no deaths among
      the participants. Seven participants had complications; 5 (18.5%) in the surgical
      group and 2 (8.3%) in the non-surgical group; the difference was not
      statistically significant (p = 0.42; Fischer's exact). Among the 27 who had
      surgery six (22.2%) surgeries were negative laparotomies, and 15 (55.6%) were non
      therapeutic. AUTHORS' CONCLUSIONS: Based on the findings of one study involving
      51 participants, which was at moderate risk of bias, there is no evidence to
      support the use of surgery over observation for people with abdominal trauma.

PMID- 23152245
TI  - Psychological therapies for the management of chronic pain (excluding headache)
      in adults.
AB  - BACKGROUND: Psychological treatments are designed to treat pain, distress and
      disability, and are in common practice. This review updates and extends the 2009
      version of this systematic review. OBJECTIVES: To evaluate the effectiveness of
      psychological therapies for chronic pain (excluding headache) in adults, compared
      with treatment as usual, waiting list control, or placebo control, for pain,
      disability, mood and catastrophic thinking. SEARCH METHODS: We identified
      randomised controlled trials (RCTs) of psychological therapy by searching
      CENTRAL, MEDLINE, EMBASE and Psychlit from the beginning of each abstracting
      service until September 2011. We identified additional studies from the reference
      lists of retrieved papers and from discussion with investigators. SELECTION
      CRITERIA: Full publications of RCTs of psychological treatments compared with an
      active treatment, waiting list or treatment as usual. We excluded studies if the
      pain was primarily headache, or was associated with a malignant disease. We also
      excluded studies if the number of patients in any treatment arm was less than 20.
      DATA COLLECTION AND ANALYSIS: Forty-two studies met our criteria and 35 (4788
      participants) provided data. Two authors rated all studies. We coded risk of bias
      as well as both the quality of the treatments and the methods using a scale
      designed for the purpose. We compared two main classes of treatment (cognitive
      behavioural therapy(CBT) and behaviour therapy) with two control conditions
      (treatment as usual; active control) at two assessment points (immediately
      following treatment and six months or more following treatment), giving eight
      comparisons. For each comparison, we assessed treatment effectiveness on four
      outcomes: pain, disability, mood and catastrophic thinking, giving a total of 32
      possible analyses, of which there were data for 25. MAIN RESULTS: Overall there
      is an absence of evidence for behaviour therapy, except a small improvement in
      mood immediately following treatment when compared with an active control. CBT
      has small positive effects on disability and catastrophising, but not on pain or
      mood, when compared with active controls. CBT has small to moderate effects on
      pain, disability, mood and catastrophising immediately post-treatment when
      compared with treatment as usual/waiting list, but all except a small effect on
      mood had disappeared at follow-up. At present there are insufficient data on the
      quality or content of treatment to investigate their influence on outcome. The
      quality of the trial design has improved over time but the quality of treatments
      has not. AUTHORS' CONCLUSIONS: Benefits of CBT emerged almost entirely from
      comparisons with treatment as usual/waiting list, not with active controls. CBT
      but not behaviour therapy has weak effects in improving pain, but only
      immediately post-treatment and when compared with treatment as usual/waiting
      list. CBT but not behaviour therapy has small effects on disability associated
      with chronic pain, with some maintenance at six months. CBT is effective in
      altering mood and catastrophising outcomes, when compared with treatment as
      usual/waiting list, with some evidence that this is maintained at six months.
      Behaviour therapy has no effects on mood, but showed an effect on catastrophising
      immediately post-treatment. CBT is a useful approach to the management of chronic
      pain. There is no need for more general RCTs reporting group means: rather,
      different types of studies and analyses are needed to identify which components
      of CBT work for which type of patient on which outcome/s, and to try to
      understand why.

PMID- 23152246
TI  - Interventions for preventing relapse and recurrence of a depressive disorder in
      children and adolescents.
AB  - BACKGROUND: Depressive disorders often begin during childhood or adolescence.
      There is a growing body of evidence supporting effective treatments during the
      acute phase of a depressive disorder. However, little is known about treatments
      for preventing relapse or recurrence of depression once an individual has
      achieved remission or recovery from their symptoms. OBJECTIVES: To determine the
      efficacy of early interventions, including psychological and pharmacological
      interventions, to prevent relapse or recurrence of depressive disorders in
      children and adolescents. SEARCH METHODS: We searched the Cochrane Depression,
      Anxiety and Neurosis Review Group's Specialised Register (CCDANCTR) (to 1 June
      2011). The CCDANCTR contains reports of relevant randomised controlled trials
      from The Cochrane Library (all years), EMBASE (1974 to date), MEDLINE (1950 to
      date) and PsycINFO (1967 to date). In addition we handsearched the references of
      all included studies and review articles. SELECTION CRITERIA: Randomised
      controlled trials using a psychological or pharmacological intervention, with the
      aim of preventing relapse or recurrence from an episode of major depressive
      disorder (MDD) or dysthymic disorder (DD) in children and adolescents were
      included. Participants were required to have been diagnosed with MDD or DD
      according to DSM or ICD criteria, using a standardised and validated assessment
      tool. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed all
      trials for inclusion in the review, extracted trial and outcome data, and
      assessed trial quality. Results for dichotomous outcomes are expressed as odds
      ratio and continuous measures as mean difference or standardised mean difference.
      We combined results using random-effects meta-analyses, with 95% confidence
      intervals. We contacted lead authors of included trials and requested additional
      data where possible. MAIN RESULTS: Nine trials with 882 participants were
      included in the review. In five trials the outcome assessors were blind to the
      participants' intervention condition and in the remainder of trials it was
      unclear. In the majority of trials, participants were either not blind to their
      intervention condition, or it was unclear whether they were or not. Allocation
      concealment was also unclear in the majority of trials. Although all trials
      treated participants in an outpatient setting, the designs implemented in trials
      was diverse, which limits the generalisability of the results. Three trials
      indicated participants treated with antidepressant medication had lower relapse
      recurrence rates (40.9%) compared to those treated with placebo (66.6%) during a
      relapse prevention phase (odds ratio (OR) 0.34; 95% confidence interval (CI) 0.18
      to 0.64, P = 0.02). One trial that compared a combination of psychological
      therapy and medication to medication alone favoured a combination approach over
      medication alone, however this result did not reach statistical significance (OR
      0.26; 95% CI 0.06 to 1.15). The majority of trials that involved antidepressant
      medication reported adverse events including suicide-related behaviours. However,
      there were not enough data to show which treatment approach results in the most
      favourable adverse event profile. AUTHORS' CONCLUSIONS: Currently, there is
      little evidence to conclude which type of treatment approach is most effective in
      preventing relapse or recurrence of depressive episodes in children and
      adolescents. Limited trials found that antidepressant medication reduces the
      chance of relapse-recurrence in the future, however, there is considerable
      diversity in the design of trials, making it difficult to compare outcomes across
      studies. Some of the research involving psychological therapies is encouraging,
      however at present more trials with larger sample sizes need to be conducted in
      order to explore this treatment approach further.

PMID- 23152247
TI  - Group versus conventional antenatal care for women.
AB  - BACKGROUND: Antenatal care is one of the key preventive health services used
      around the world. In most Western countries, antenatal care traditionally
      involves a schedule of one-to-one visits with a care provider. A different way of
      providing antenatal care is through a group model. OBJECTIVES: The first
      objective was to compare the effects of group antenatal care versus one-to-one
      care on outcomes for women and their babies. The primary outcomes were preterm
      birth (birth occurring before 37 completed gestational weeks), low birthweight
      (less than 2500 g), small-for-gestational age (less than the tenth percentile for
      gestation and gender) and perinatal mortality. Secondary outcomes included
      psychological measures and satisfaction as well as labour and birth and postnatal
      outcomes.The second objective was to compare the effects of group care versus one
      to-one care on care provider satisfaction. SEARCH METHODS: We searched the
      Cochrane Pregnancy and Childbirth Group's Trials Register (9 March 2012),
      contacted experts in the field and reviewed the reference lists of retrieved
      studies. SELECTION CRITERIA: All identified published, unpublished and ongoing
      randomised and quasi-randomised controlled trials comparing group antenatal care
      with conventional antenatal care were included. Cluster-randomised trials were
      eligible for inclusion but none were identified. Cross-over trials were not
      eligible. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed
      studies for inclusion and evaluated trial quality. Two authors extracted data.
      Data were checked for accuracy. MAIN RESULTS: We included two studies (1369
      women). There were no statistically significant differences between women who
      received group antenatal care compared with standard one-to-one care in relation
      to the primary outcomes. In particular, there was no difference in the rate of
      preterm birth rate between the two groups (risk ratio (RR) 0.87; 95% confidence
      interval (CI) 0.47 to 1.60; two trials; N = 1315) and the proportion of low
      birthweight (less than 2500 g) babies was similar between the groups (RR 1.03;
      95% CI 0.73 to 1.46; two trials; N = 1315).Satisfaction was rated highly in women
      who were allocated to group antenatal care but only measured in one trial. In
      this trial, the mean satisfaction with care in group antenatal care was almost
      five times higher compared with those allocated to standard care (N = 993). A
      number of outcomes related to stress, distress and depression were reported in
      one trial. There were no differences between the groups in any of these
      outcomes.There were no data available on the effects of group antenatal care on
      care provider satisfaction. AUTHORS' CONCLUSIONS: The available evidence suggests
      that group antenatal care is positively viewed by women with no adverse outcomes
      for themselves or their babies. This review is limited owing to the small number
      of studies/women and the majority of the analyses are based on a single study.
      More research is required to determine if group antenatal care is associated with
      significant benefits.

PMID- 23152248
TI  - Gene therapy for sickle cell disease.
AB  - BACKGROUND: Sickle cell disease encompasses a group of genetic disorders
      characterized by the presence of at least one hemoglobin S (Hb S) allele, and a
      second abnormal allele that could allow abnormal hemoglobin polymerisation
      leading to a symptomatic disorder.Autosomal recessive disorders (such as sickle
      cell disease) are good candidates for gene therapy because a normal phenotype can
      be restored in diseased cells with only a single normal copy of the mutant gene.
      OBJECTIVES: The objectives of this review are:- to determine whether gene therapy
      can improve survival and prevent symptoms and complications associated with
      sickle cell disease;- to examine the risks of gene therapy against the potential
      long-term gain for people with sickle cell disease. SEARCH METHODS: We searched
      the Cochrane Cystic Fibrosis and Genetic Disorders Group Haemoglobinopathies
      Trials Register, which comprises of references identified from comprehensive
      electronic database searches and searching relevant journals and abstract books
      of conference proceedings.Date of the most recent search of the Group's
      Haemoglobinopathies Trials Register: 21 June 2012. SELECTION CRITERIA: All
      randomised or quasi-randomised clinical trials (including any relevant phase 1, 2
      or 3 trials) of gene therapy for all individuals with sickle cell disease,
      regardless of age or setting. DATA COLLECTION AND ANALYSIS: No trials of gene
      therapy for sickle cell disease were found. MAIN RESULTS: No trials of gene
      therapy for sickle cell disease were reported. AUTHORS' CONCLUSIONS: No
      randomised or quasi-randomised clinical trials of gene therapy for sickle cell
      disease were reported. Thus, no objective conclusions or recommendations in
      practice can be made on gene therapy for sickle cell disease. This systematic
      review has identified the need for well-designed, randomised controlled trials to
      assess the benefits and risks of gene therapy for sickle cell disease.

PMID- 23152249
TI  - Email for clinical communication between patients/caregivers and healthcare
      professionals.
AB  - BACKGROUND: Email is a popular and commonly-used method of communication, but its
      use in health care is not routine. Where email communication has been
      demonstrated in health care this has included its use for communication between
      patients/caregivers and healthcare professionals for clinical purposes, but the
      effects of using email in this way is not known.This review addresses the use of
      email for two-way clinical communication between patients/caregivers and
      healthcare professionals. OBJECTIVES: To assess the effects of healthcare
      professionals and patients using email to communicate with each other, on patient
      outcomes, health service performance, service efficiency and acceptability.
      SEARCH METHODS: We searched: the Cochrane Consumers and Communication Review
      Group Specialised Register, Cochrane Central Register of Controlled Trials
      (CENTRAL, The Cochrane Library, Issue 1 2010), MEDLINE (OvidSP) (1950 to January
      2010), EMBASE (OvidSP) (1980 to January 2010), PsycINFO (OvidSP) (1967 to January
      2010), CINAHL (EbscoHOST) (1982 to February 2010) and ERIC (CSA) (1965 to January
      2010). We searched grey literature: theses/dissertation repositories, trials
      registers and Google Scholar (searched July 2010). We used additional search
      methods: examining reference lists, contacting authors. SELECTION CRITERIA:
      Randomised controlled trials, quasi-randomised trials, controlled before and
      after studies and interrupted time series studies examining interventions using
      email to allow patients to communicate clinical concerns to a healthcare
      professional and receive a reply, and taking the form of 1) unsecured email 2)
      secure email or 3) web messaging. All healthcare professionals, patients and
      caregivers in all settings were considered. DATA COLLECTION AND ANALYSIS: Two
      authors independently assessed the risk of bias of included studies and extracted
      data. We contacted study authors for additional information. We assessed risk of
      bias according to the Cochrane Handbook for Systematic Reviews of Interventions.
      For continuous measures, we report effect sizes as mean differences (MD). For
      dichotomous outcome measures, we report effect sizes as odds ratios and rate
      ratios. Where it was not possible to calculate an effect estimate we report mean
      values for both intervention and control groups and the total number of
      participants in each group. Where data are available only as median values it is
      presented as such. It was not possible to carry out any meta-analysis of the
      data. MAIN RESULTS: We included nine trials enrolling 1733 patients; all trials
      were judged to be at risk of bias. Seven were randomised controlled trials; two
      were cluster-randomised controlled designs. Eight examined email as compared to
      standard methods of communication. One compared email with telephone for the
      delivery of counselling. When email was compared to standard methods, for the
      majority of patient/caregiver outcomes it was not possible to adequately assess
      whether email had any effect. For health service use outcomes it was not possible
      to adequately assess whether email has any effect on resource use, but some
      results indicated that an email intervention leads to an increased number of
      emails and telephone calls being received by healthcare professionals. Three
      studies reported some type of adverse event but it was not clear if the adverse
      event had any impact on the health of the patient or the quality of health care.
      When email counselling was compared to telephone counselling only patient
      outcomes were measured, and for the majority of measures there was no difference
      between groups. Where there were differences these showed that telephone
      counselling leads to greater change in lifestyle modification factors than email
      counselling. There was one outcome relating to harm, which showed no difference
      between the email and the telephone counselling groups. There were no primary
      outcomes relating to healthcare professionals for either comparison. AUTHORS'
      CONCLUSIONS: The evidence base was found to be limited with variable results and
      missing data, and therefore it was not possible to adequately assess the effect
      of email for clinical communication between patients/caregivers and healthcare
      professionals. Recommendations for clinical practice could not be made. Future
      research should ideally address the issue of missing data and methodological
      concerns by adhering to published reporting standards. The rapidly changing
      nature of technology should be taken into account when designing and conducting
      future studies and barriers to trial development and implementation should also
      be tackled. Potential outcomes of interest for future research include cost
      effectiveness and health service resource use.

PMID- 23152250
TI  - Email for the provision of information on disease prevention and health
      promotion.
AB  - BACKGROUND: Email is a popular and commonly used method of communication, but its
      use in health care is not routine. Its application in health care has included
      the provision of information on disease prevention and health promotion, but the
      effects of using email in this way are not known. This review assesses the use of
      email for the provision of information on disease prevention and health
      promotion. OBJECTIVES: To assess the effects of email for the provision of
      information on disease prevention and health promotion, compared to standard mail
      or usual care, on outcomes for healthcare professionals, patients and caregivers,
      and health services, including harms. SEARCH METHODS: We searched: the Cochrane
      Consumers and Communication Review Group Specialised Register (January 2010), the
      Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library,
      Issue 1 2010), MEDLINE (1950 to January 2010), EMBASE (1980 to January 2010),
      CINAHL (1982 to February 2010), ERIC (1965 to January 2010) and PsycINFO (1967 to
      January 2010). We searched grey literature: theses/dissertation repositories,
      trials registers and Google Scholar (searched July 2010). We used additional
      search methods: examining reference lists, contacting authors. SELECTION
      CRITERIA: Randomised controlled trials, quasi-randomised trials, controlled
      before and after studies and interrupted time series studies examining
      interventions where email is used by healthcare professionals to provide
      information to patients on disease prevention and health promotion, and taking
      the form of 1) unsecured email 2) secure email or 3) web messaging. We considered
      healthcare professionals or associated administrative staff as participants
      originating the email communication, and patients and caregivers as participants
      receiving the email communication, in all settings. Email communication was one
      way from healthcare professionals or associated administrative staff originating
      the email communication, to patients or caregivers receiving the email
      communication. DATA COLLECTION AND ANALYSIS: Two authors independently assessed
      the risk of bias of included studies and extracted data. We contacted study
      authors for additional information. We assessed risk of bias according to the
      Cochrane Handbook for Systematic Reviews of Interventions. For continuous outcome
      measures, we report effect sizes as mean differences (MDs). For dichotomous
      outcome measures, we report effect sizes as odds ratios (ORs). We conducted a
      meta-analysis for one primary health service outcome, comparing email
      communication to standard mail, and report this result as an OR. MAIN RESULTS: We
      included six randomised controlled trials involving 8372 people. All trials were
      judged to be at high risk of bias for at least one domain. Four trials compared
      email communication to standard mail and two compared email communication to
      usual care. For the primary health service outcome of uptake of preventive
      screening, there was no difference between email and standard mail (OR 0.93; 95%
      CI 0.69 to 1.24). For both comparisons (email versus standard mail and email
      versus usual care) there was no difference between the groups for patient or
      caregiver understanding and support. Results were inconclusive for patient or
      caregiver behaviours and actions. For email versus usual care only, there was no
      significant difference between groups for the primary outcome of patient health
      status and well-being. No data were reported relating to healthcare professionals
      or harms. AUTHORS' CONCLUSIONS: The evidence on the use of email for the
      provision of information on disease prevention and health promotion was weak, and
      therefore inadequate to inform clinical practice. The available trials mostly
      provide inconclusive, or no evidence for the outcomes of interest in this review.
      Future research needs to use high-quality study designs that take advantage of
      the most recent developments in information technology, with consideration of the
      complexity of email as an intervention.

PMID- 23152251
TI  - Methadone for chronic non-cancer pain in adults.
AB  - BACKGROUND: Methadone belongs to a class of analgesics known as opioids, that are
      considered the cornerstone of therapy for moderate-to-severe pain due to life
      threatening illnesses; however, their use in chronic non-cancer pain (CNCP) is
      controversial. Methadone has many characteristics that differentiate it from
      other opioids, which suggests that it may have a different efficacy and safety
      profile. OBJECTIVES: To assess the analgesic effectiveness and safety of
      methadone in the treatment of CNCP. SEARCH METHODS: We identified both randomized
      controlled trials (RCTs) and non-randomized studies of methadone use in chronic
      pain by searching the Cochrane Central Register of Controlled Trials (CENTRAL) in
      The Cochrane Library 2011, issue 11, MEDLINE (1950 to November 2011), and EMBASE
      (1980 to November 2011), together with reference lists of retrieved papers and
      reviews. SELECTION CRITERIA: We included RCTs with pain assessment as either the
      primary or secondary outcome. Quasi-randomized studies, cohorts and case-control
      trials were also considered for inclusion because we suspected that the
      beneficial and harmful effects of methadone in CNCP may not be adequately
      addressed in RCTs. DATA COLLECTION AND ANALYSIS: Two review authors independently
      extracted efficacy and adverse event data and assessed risk of bias. MAIN
      RESULTS: We included two RCTs and one non-randomized study, involving a total of
      181 participants. Both RCTs were cross-over studies, one involving 19
      participants with diverse neuropathic pain syndromes, the other involving 76
      participants with postherpetic neuralgia. Study phases were 20 days and
      approximately eight weeks, respectively. The non-randomized study retrospectively
      evaluated 86 outpatients over an average of 8.8 +/- 6.3 months.One RCT reported
      average pain intensity and pain relief, and found statistically significant
      improvements versus placebo for both outcomes, with 10 mg and 20 mg daily doses
      of methadone. The second RCT reported differences in pain reduction between
      methadone and morphine and found morphine to be statistically superior. The non
      randomized study found that in patients initially prescribed methadone it was
      effective in fewer participants than in those initially prescribed other long
      acting opioids (28% versus 42%, 33% and 50% for morphine, oxycodone and
      transdermal fentanyl, respectively).One RCT compared incidences for several
      individual adverse events, but found a difference between methadone and placebo
      for only one event, dizziness (P = 0.041). AUTHORS' CONCLUSIONS: The three
      studies provide very limited evidence of the efficacy of methadone for CNCP, and
      there were too few data for pooled analysis of efficacy or harm, or to have
      confidence in the results of the individual studies. No conclusions can be made
      regarding differences in efficacy or safety between methadone and placebo, other
      opioids, or other treatments.

PMID- 23152252
TI  - Reduction versus abrupt cessation in smokers who want to quit.
AB  - BACKGROUND: The standard way to stop smoking is to quit abruptly on a designated
      quit day. A number of smokers have tried unsuccessfully to quit this way.
      Reducing smoking before quitting could be an alternative approach to cessation.
      Before this method is adopted it is important to determine whether it is at least
      as successful as abrupt quitting. OBJECTIVES: 1. To compare the success of
      reducing smoking to quit and abrupt quitting interventions. 2. To compare adverse
      events between arms in studies that used pharmacotherapy to aid reduction. SEARCH
      METHODS: We searched the Cochrane Tobacco Addiction Review Group specialised
      register using topic specific terms. The register contains reports of trials of
      tobacco addiction interventions identified from searches of MEDLINE, EMBASE and
      PsycInfo. We also searched reference lists of relevant papers and contacted
      authors of ongoing trials. Date of most recent search: July 2012. SELECTION
      CRITERIA: We included randomized controlled trials (RCTs) that recruited adults
      who wanted to quit smoking. Studies included at least one condition which
      instructed participants to reduce their smoking and then quit and one condition
      which instructed participants to quit abruptly. DATA COLLECTION AND ANALYSIS: The
      outcome measure was abstinence from smoking after at least six months follow-up.
      We pooled the included trials using a Mantel-Haenszel fixed-effect model. Trials
      were split for two sub-group analyses: pharmacotherapy vs no pharmacotherapy,
      self help therapy vs behavioural support. Adverse events were summarised as a
      narrative. It was not possible to compare them quantitatively as there was
      variation in the nature and depth of reporting across studies. MAIN RESULTS: Ten
      studies were relevant for inclusion, with a total of 3760 participants included
      in the meta-analysis. Three of these studies used pharmacotherapy as part of the
      interventions. Five studies included behavioural support in the intervention,
      four included self-help therapy, and the remaining study had arms which included
      behavioural support and arms which included self-help therapy. Neither reduction
      or abrupt quitting had superior abstinence rates when all the studies were
      combined in the main analysis (RR= 0.94, 95% CI= 0.79 to 1.13), whether
      pharmacotherapy was used (RR= 0.87, 95% CI= 0.65 to 1.22), or not (RR= 0.97, 95%
      CI= 0.78 to 1.21), whether studies included behavioural support (RR= 0.87, 95%
      CI= 0.64 to 1.17) or self-help therapy (RR= 0.98, 95% CI= 0.78 to1.23). We were
      unable to draw conclusions about the difference in adverse events between
      interventions, however recent studies suggest that pre-quit NRT does not increase
      adverse events. AUTHORS' CONCLUSIONS: Reducing cigarettes smoked before quit day
      and quitting abruptly, with no prior reduction, produced comparable quit rates,
      therefore patients can be given the choice to quit in either of these ways.
      Reduction interventions can be carried out using self-help materials or aided by
      behavioural support, and can be carried out with the aid of pre-quit NRT. Further
      research needs to investigate which method of reduction before quitting is the
      most effective, and which categories of smokers benefit the most from each
      method, to inform future policy and intervention development.

PMID- 23152253
TI  - Rituximab, ofatumumab and other monoclonal anti-CD20 antibodies for chronic
      lymphocytic leukaemia.
AB  - BACKGROUND: Chronic lymphocytic leukaemia (CLL) accounts for 25% of all
      leukaemias and is the most common lymphoid malignancy in western countries.
      Standard treatments include mono- or polychemotherapies, usually combined with
      monoclonal antibodies such as rituximab or alemtuzumab. However, the impact of
      these agents remains unclear, as there are hints for increased risk of severe
      infections. OBJECTIVES: The objectives of this review are to provide an evidence
      based answer regarding the clinical benefits and harms of monoclonal anti-CD20
      antibodies (such as rituximab, ofatumumab, GA101) compared to no further therapy
      or to other anti-leukaemic therapies in patients with CLL, irrespective of
      disease status. SEARCH METHODS: We searched the Cochrane Central Register of
      Controlled Trials (The Cochrane Library Issue 12, 2011), MEDLINE (from January
      1990 to 4 January 2012), and EMBASE (from 1990 to 20 March 2009) as well as
      conference proceedings (American Society of Hematology, American Society of
      Clinical Oncology, European Hematology Association and European Society of
      Medical Oncology) for randomised controlled trials (RCTs). SELECTION CRITERIA: We
      included RCTs examining monoclonal anti-CD20 antibodies compared to no further
      therapy or to anti-leukaemic therapy such as chemotherapy or monoclonal
      antibodies in patients with newly diagnosed or relapsed CLL. DATA COLLECTION AND
      ANALYSIS: We used hazard ratios (HR) as effect measures for overall survival
      (OS), progression-free survival (PFS) and time to next treatment, and risk ratios
      (RR) for response rates, treatment-related mortality (TRM) and adverse events
      (AEs). Two review authors independently extracted data and assessed quality of
      trials. MAIN RESULTS: We screened a total of 1150 records. Seven RCTs involving
      1763 patients were identified, but only five could be included in the two
      separate meta-analyses we performed. We judged the overall the quality of these
      trials as moderate to high. All trials were randomised and open-label studies.
      However, two trials were published as abstracts only, therefore we were unable to
      assess the potential risk of bias for these trials in detail.Three RCTs (N =
      1421) assessed the efficacy of monoclonal anti-CD20 antibodies (i.e. rituximab)
      plus chemotherapy compared to chemotherapy alone. The meta-analyses showed a
      statistically significant OS (HR 0.78, 95% confidence interval (CI) 0.62 to 0.98,
      P = 0.03, the number needed to treat for an additional beneficial effect (NNTB)
      was 12) and PFS (HR 0.64, 95% CI 0.55 to 0.74, P < 0.00001) advantage for
      patients receiving rituximab. In the rituximab-arm occurred more AEs, World
      Health Organization (WHO) grade 3 or 4 (3 trials, N = 1398, RR 1.15, 95% CI 1.08
      to 1.23, P < 0.0001; the number needed to harm for an additional harmful outcome
      (NNTH) was 9), but that did not lead to a statistically significant difference
      regarding TRM (3 trials, N = 1415, RR 1.19, 95% CI 0.70 to 2.01, P = 0.52).Two
      trials (N = 177) evaluated rituximab versus alemtuzumab. Neither study reported
      OS or PFS. There was no statistically significant difference between arms
      regarding complete response rate (CRR) (RR 1.21, 95% CI 0.94 to 1.58, P = 0.14)
      or TRM (RR 0.31, 95% CI 0.06 to 1.51, P = 0.15). However, the CLL2007FMP trial
      was stopped early owing to an increase in mortality in the alemtuzumab arm. More
      serious AEs occurred in this arm (43% with alemtuzumab versus 22% with rituximab;
      P = 0.006).Two trials assessed different dosages or time schedules of monoclonal
      anti-CD20 antibodies. One trial (N = 104) evaluated two different rituximab
      schedules (concurrent arm: fludarabine plus rituximab (Flu-R) plus rituximab
      consolidation versus sequential arm: fludarabine alone plus rituximab
      consolidation). The comparison of the concurrent versus sequential regimen of
      rituximab showed a statistically significant difference of the CRR with 33% in
      the concurrent-arm and 15% in the sequential-arm (P = 0.04), that did not lead to
      statistically significant differences regarding OS (HR 1.14, 95% CI 0.20 to 6.65,
      P = 0.30) or PFS (HR 0.96, 95% CI 0.43 to 2.15, P = 0.11). Furthermore results
      showed no differences in occurring AEs, except for neutropenia, which was more
      often observed in patients of the concurrent arm. The other trial (N = 61)
      investigated two different dosages (500 mg and 1000 mg) of ofatumumab in addition
      to FluC. The arm investigating ofatumumab did not assess OS and a median PFS had
      not been reached owing to the short median follow-up of eight months. It showed
      no statistically significant differences between arms regarding CRR (32% in the
      FCO500 arm versus 50% in the FCO1000 arm; P = 0.10) or AEs (anaemia, neutropenia,
      thrombocytopenia). AUTHORS' CONCLUSIONS: This meta-analysis showed that patients
      receiving chemotherapy plus rituximab benefit in terms of OS as well as PFS
      compared to those with chemotherapy alone. Therefore, it supports the
      recommendation of rituximab in combination with FluC as an option for the first
      line treatment as well as for the people with relapsed or refractory CLL. The
      available evidence regarding the other assessed comparisons was not sufficient to
      deduct final conclusions.

PMID- 23152254
TI  - Blood pressure lowering efficacy of potassium-sparing diuretics (that block the
      epithelial sodium channel) for primary hypertension.
AB  - BACKGROUND: Potassium-sparing diuretics, which block the epithelial sodium
      channel (ENaC), are widely prescribed for hypertension as a second-line drug in
      patients taking other diuretics (e.g. thiazide diuretics) and much less commonly
      prescribed as monotherapy. Therefore, it is essential to determine the effects of
      ENaC blockers on blood pressure (BP), heart rate and withdrawals due to adverse
      effects (WDAEs) when given as a first-line or second-line therapy. OBJECTIVES: To
      quantify the dose-related reduction in systolic blood pressure (SBP) and
      diastolic blood pressure (DBP) of ENaC blocker therapy as a first-line or second
      line drug in patients with primary hypertension. SEARCH METHODS: We searched
      CENTRAL (The Cochrane Library 2012), MEDLINE (1950 to August 2012), EMBASE (1980
      to August 2012) and reference lists of articles. SELECTION CRITERIA: Double
      blind, randomized, controlled trials in patients with primary hypertension that
      evaluate, for a duration of 3 to 12 weeks, the BP lowering efficacy of: 1) fixed
      dose monotherapy with an ENaC blocker compared with placebo; or 2) an ENaC
      blocker in combination with another class of anti-hypertensive drugs compared
      with the respective monotherapy (without an ENaC blocker). DATA COLLECTION AND
      ANALYSIS: Two authors independently assessed the risk of bias and extracted data.
      Study authors were contacted for additional information. WDAE information was
      also collected from the trials. MAIN RESULTS: No trials evaluating the BP
      lowering efficacy of ENaC blockers as monotherapy in patients with primary
      hypertension were identified. Only 6 trials evaluated the BP lowering efficacy of
      low doses of amiloride and triamterene as a second drug in 496 participants with
      a baseline BP of 151/102 mm Hg. The additional BP reduction caused by the ENaC
      blocker as a second drug was estimated by comparing the difference in BP
      reduction between the combination and monotherapy groups. The addition of low
      doses of amiloride and triamterene in these trials did not reduce BP. An estimate
      of the dose-related BP lowering efficacy for ENaC blockers was not possible
      because of a lack of trial data at higher doses. AUTHORS' CONCLUSIONS: ENaC
      blockers do not have a statistically or clinically significant BP lowering effect
      at low doses but trials at higher doses are not available. The review did not
      provide a good estimate of the incidence of harms associated with ENaC blockers.

PMID- 23152255
TI  - Psychological therapies versus antidepressant medication, alone and in
      combination for depression in children and adolescents.
AB  - BACKGROUND: Depressive disorders are common in children and adolescents and, if
      left untreated, are likely to recur in adulthood. Depression is highly
      debilitating, affecting psychosocial, family and academic functioning.
      OBJECTIVES: To evaluate the effectiveness of psychological therapies and
      antidepressant medication, alone and in combination, for the treatment of
      depressive disorder in children and adolescents. We have examined clinical
      outcomes including remission, clinician and self reported depression measures,
      and suicide-related outcomes. SEARCH METHODS: We searched the Cochrane
      Depression, Anxiety and Neurosis Review Group's Specialised Register (CCDANCTR)
      to 11 November 2011. This register contains reports of relevant randomised
      controlled trials (RCTs) from the Cochrane Central Register of Controlled Trials
      (CENTRAL), MEDLINE (1950 to date), EMBASE (1974 to date), and PsycINFO (1967 to
      date). SELECTION CRITERIA: RCTs were eligible for inclusion if they compared i)
      any psychological therapy with any antidepressant medication, or ii) a
      combination of psychological therapy and antidepressant medication with a
      psychological therapy alone, or an antidepressant medication alone, or iii) a
      combination of psychological therapy and antidepressant medication with a placebo
      or 'treatment as usual', or (iv) a combination of psychological therapy and
      antidepressant medication with a psychological therapy or antidepressant
      medication plus a placebo.We included studies if they involved participants aged
      between 6 and 18 years, diagnosed by a clinician as having Major Depressive
      Disorder (MDD) based on Diagnostic and Statistical Manual (DSM) or International
      Classification of Diseases (ICD) criteria. DATA COLLECTION AND ANALYSIS: Two
      review authors independently selected studies, extracted data and assessed the
      quality of the studies. We applied a random-effects meta-analysis, using the odds
      ratio (OR) to describe dichotomous outcomes, mean difference (MD) to describe
      continuous outcomes when the same measures were used, and standard mean
      difference (SMD) when outcomes were measured on different scales. MAIN RESULTS:
      We included ten studies, involving 1235 participants in this review. Studies
      recruited participants with different severities of disorder and with a variety
      of comorbid disorders, including anxiety and substance use disorder, therefore
      limiting the comparability of the results. Regarding the risk of bias in studies,
      half the studies had adequate allocation concealment (there was insufficient
      information to determine allocation concealment in the remainder), outcome
      assessors were blind to the participants' intervention in six studies, and in
      general, studies reported on incomplete data analysis methods, mainly using
      intention-to-treat (ITT) analyses. For the majority of outcomes there were no
      statistically significant differences between the interventions compared. There
      was limited evidence (based on two studies involving 220 participants) that
      antidepressant medication was more effective than psychotherapy on measures of
      clinician defined remission immediately post-intervention (odds ratio (OR) 0.52,
      95% confidence interval (CI) 0.27 to 0.98), with 67.8% of participants in the
      medication group and 53.7% in the psychotherapy group rated as being in
      remission. There was limited evidence (based on three studies involving 378
      participants) that combination therapy was more effective than antidepressant
      medication alone in achieving higher remission from a depressive episode
      immediately post-intervention (OR 1.56, 95% CI 0.98 to 2.47), with 65.9% of
      participants treated with combination therapy and 57.8% of participants treated
      with medication, rated as being in remission. There was no evidence to suggest
      that combination therapy was more effective than psychological therapy alone,
      based on clinician rated remission immediately post-intervention (OR 1.82, 95% CI
      0.38 to 8.68).Suicide-related Serious Adverse Events (SAEs) were reported in
      various ways across studies and could not be combined in meta-analyses. However
      suicidal ideation specifically was generally measured and reported using
      standardised assessment tools suitable for meta-analysis. In one study involving
      188 participants, rates of suicidal ideation were significantly higher in the
      antidepressant medication group (18.6%) compared with the psychological therapy
      group (5.4%) (OR 0.26, 95% CI 0.09 to 0.72) and this effect appeared to remain at
      six to nine months (OR 1.27, 95% CI 0.68 to 2.36), with 13.6% of participants in
      the medication group and 3.9% of participants in the psychological therapy group
      reporting suicidal ideation. It was unclear what the effect of combination
      therapy was compared with either antidepressant medication alone or psychological
      therapy alone on rates of suicidal ideation. The impact of any of the assigned
      treatment packages on drop out was also mostly unclear across the various
      comparisons in the review.Limited data and conflicting results based on other
      outcome measures make it difficult to draw conclusions regarding the
      effectiveness of any specific intervention based on these outcomes. AUTHORS'
      CONCLUSIONS: There is very limited evidence upon which to base conclusions about
      the relative effectiveness of psychological interventions, antidepressant
      medication and a combination of these interventions. On the basis of the
      available evidence, the effectiveness of these interventions for treating
      depressive disorders in children and adolescents cannot be established. Further
      appropriately powered RCTs are required.

PMID- 23152256
TI  - Interventions for treating leg ulcers in people with sickle cell disease.
AB  - BACKGROUND: The frequency of skin ulceration makes it an important contributor to
      the morbidity burden in people with sickle cell disease. Many treatment options
      are available to the healthcare professional, although it is uncertain which
      treatments have been assessed for effectiveness in people with sickle cell
      disease. OBJECTIVES: To assess the clinical effectiveness and safety of
      interventions for treating leg ulcers in people with sickle cell disease. SEARCH
      METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's
      Haemoglobinopathies Trials Register.We searched LILACS (1982 to August 2012), the
      African Index Medicus (up to August 2012), ISI Web of Knowledge (1985 to August
      2012), and the Clinical Trials Search Portal of the World Health Organization
      (August 2012). We checked the reference lists of all the trials identified. We
      also contacted those groups or individuals who may have completed relevant
      randomised trials in this area.Date of the last search of the Group's
      Haemoglobinopathies Trials Register: 25 May 2012. SELECTION CRITERIA: Randomised
      controlled trials of interventions for treating leg ulcers in people with sickle
      cell disease compared to placebo or an alternative treatment. DATA COLLECTION AND
      ANALYSIS: Two authors independently selected studies for inclusion. All three
      authors independently assessed the risk of bias of the included studies and
      extracted data. MAIN RESULTS: Six studies met the inclusion criteria (198
      participants with 250 ulcers). Each trial investigated a different intervention
      and within this review we have grouped these as systemic pharmaceutical
      interventions (L-cartinine, arginine butyrate, isoxsuprine) and topical
      pharmaceutical interventions (Solcoseryl((r)) cream, RGD peptide dressing,
      topical antibiotics). Three interventions reported on the change in ulcer size
      (arginine butyrate, RGD peptide, L-cartinine). Of these, RGD peptide matrix
      significantly reduced ulcer size compared with a control group, mean reduction
      6.60cm(2) (95% CI 5.51 to 7.69). Three trials reported on the incidence of
      complete closure (isoxsuprine, arginine butyrate, RGD peptide matrix). None
      reported a significant effect. No trial reported on: the time to complete ulcer
      healing; ulcer-free survival following treatment for sickle cell leg ulcers;
      quality of life measures; or incidence of amputation. There was no reported
      information on the safety of these interventions. AUTHORS' CONCLUSIONS: There is
      evidence that a topical intervention (RGD peptide matrix) reduced ulcer size in
      treated participants compared to controls. This evidence of efficacy is limited
      by the generally high risk of bias associated with these reports.We planned to
      analyse results according to general groups: pharmaceutical interventions
      (systemic and topical); and non-pharmaceutical interventions (surgical and non
      surgical). However, we were unable to pool findings due to the heterogeneity in
      outcome definitions, and inconsistency between the unit of randomisation and the
      unit of analysis. This heterogeneity, along with a paucity of identified trials,
      prevented us performing any meta-analyses.This Cochrane review provides some
      evidence for the effectiveness of one topical intervention - RGD peptide matrix.
      However, this intervention was assessed as having a high risk of bias due to
      inadequacies in the single trial report. Other included studies were also
      assessed as having a high risk of bias. We recommend that readers interpret the
      trial results with caution. The safety profile of the all interventions was
      inconclusive.

PMID- 23152257
TI  - Nebulised deoxyribonuclease for viral bronchiolitis in children younger than 24
      months.
AB  - BACKGROUND: Bronchiolitis is one of the most common respiratory problems in the
      first year of life. The sputum of infants with bronchiolitis has increased
      deoxyribonucleic acid (DNA) content, leading to mucous plugging and airway
      obstruction. Recombinant human deoxyribonuclease (rhDNase), an enzyme that
      digests extracellular DNA, might aid the clearance of mucus and relieve
      peripheral airway obstruction. OBJECTIVES: To determine the effect of nebulised
      rhDNase on the severity and duration of viral bronchiolitis in children younger
      than 24 months of age in the hospital setting. SEARCH METHODS: We searched the
      Cochrane Central Register of Controlled Trials (CENTRAL) 2012, Issue 7 which
      includes the Acute Respiratory Infections Group's Specialised Register, MEDLINE
      (1966 to July Week 4, 2012), EMBASE (1974 to August 2012) and LILACS (1982 to
      August 2012). SELECTION CRITERIA: Randomised controlled trials (RCTs) using
      nebulised rhDNase alone or with concomitant therapy in children younger than 24
      months of age hospitalised with acute bronchiolitis. DATA COLLECTION AND
      ANALYSIS: Two review authors independently performed literature searches,
      assessed trial quality and extracted data. We obtained unpublished data from
      trial authors. We used Review Manager 5.1 to pool treatment effects expressed as
      the mean difference (MD) or standardised mean difference (SMD) with 95%
      confidence intervals (CI). MAIN RESULTS: Three RCTs (333 participants) were
      identified, two of which were multicentre trials comprising only participants
      positive for respiratory syncytial virus (RSV). The other trial enrolled
      participants clinically diagnosed with bronchiolitis from a hospital in Italy.
      All studies used 2.5 mL (1 mg/mL) of nebulised rhDNase compared with placebo
      either as a daily or a twice daily dose. Adjunctive therapy included nebulised
      salbutamol, steroids, supplemental oxygen, intravenous fluids or tube feeding,
      nasal washing, nasal decongestants and antibiotics.Overall, nebulised rhDNase
      showed no benefit in clinically meaningful outcomes. Meta-analysis favoured the
      control group with a shorter duration of hospital stay (MD 0.50; 95% CI 0.10 to
      0.90, P = 0.01) and better clinical score improvement (SMD -0.24; 95% CI -0.50 to
      0.01, P = 0.06). The largest trial showed no difference in supplemental oxygen
      use or intensive care unit (ICU) admission.In one RCT, four out of 11 patients in
      the treatment group had atelectasis. Two of these patients showed distinctive
      clinical improvement after nebulised rhDNase.There was no significant difference
      in adverse events. These included temporary desaturation, temporary coughing,
      increased coughing, facial rash, hoarseness, dyspnoea and bad taste, reported in
      a total of 11 patients from both treatment groups. AUTHORS' CONCLUSIONS: The
      results based on the three included studies in this review did not support the
      use of nebulised rhDNase in children under 24 months of age hospitalised with
      acute bronchiolitis. In these patients, treatment did not shorten the length of
      hospitalisation or improve clinical outcomes. It might have a role in severe
      bronchiolitis complicated by atelectasis, but further clinical studies would need
      to be performed.

PMID- 23152258
TI  - Double-bundle versus single-bundle reconstruction for anterior cruciate ligament
      rupture in adults.
AB  - BACKGROUND: Arthroscopic reconstruction for anterior cruciate ligament rupture is
      a common orthopaedic procedure. One area of controversy is whether the method of
      double-bundle reconstruction, which represents the 'more anatomical' approach,
      gives improved outcomes compared with the more traditional single-bundle
      reconstruction. OBJECTIVES: To assess the effects of double-bundle versus single
      bundle for anterior cruciate ligament reconstruction in adults with anterior
      cruciate ligament deficiency. SEARCH METHODS: We searched the Cochrane Bone,
      Joint and Muscle Trauma Group Specialised Register (to February 2012), the
      Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library
      2012, Issue 2), MEDLINE (1966 to February week 3 2012) and EMBASE (1980 to 2012
      Week 8). We also searched trial registers, conference proceedings, and contacted
      authors where necessary. SELECTION CRITERIA: Randomised and quasi-randomised
      controlled clinical trials comparing double-bundle versus single-bundle
      reconstruction for anterior cruciate ligament (ACL) rupture in adults. DATA
      COLLECTION AND ANALYSIS: Two review authors independently selected articles,
      assessed risk of bias and extracted data. We contacted investigators to obtain
      missing information. Where appropriate, results of comparable studies were
      pooled. MAIN RESULTS: Seventeen trials were included. These involved 1433 people,
      mostly young physically active adults. All included trials had methodological
      weaknesses and were at risk of bias, notably selection bias from inadequate or
      lack of allocation concealment. Data for pooling individual outcomes were
      available for a maximum of nine trials and 54% of participants.There were no
      statistically or clinically significant differences between double-bundle and
      single-bundle reconstruction in the subjective functional knee scores (subjective
      IKDC score, Tegner activity score, Lysholm score) in the intermediate (six months
      up to two years since surgery) or long term (two to five years from surgery). For
      example, the long term results for the Lysholm score (0 to 100: best score) were:
      mean difference (MD) 0.12, 95% confidence interval (CI) -1.50 to 1.75; 5 trials,
      263 participants). The only trial reporting on long term knee pain found no
      statistically significant differences between the two groups. There were no
      significant differences between the two groups in adverse effects and
      complications (e.g. infection reported by nine trials (7/285 versus 7/393; risk
      ratio (RR) 1.14, 95% CI 0.46 to 2.81); graft failure reported by six trials
      (1/169 versus 4/185; RR 0.45; 95% CI 0.07 to 2.90).Limited data from five trials
      found a better return to pre-injury level of activity after double-bundle
      reconstruction (147/162 versus 208/255; RR 1.15, 95% CI 1.07 to 1.25). At long
      term follow-up, there were statistically significant differences in favour of
      double-bundle reconstruction for IKDC knee examination (normal or nearly normal
      categories: 325/344 versus 386/429; RR 1.05, 95% CI 1.01 to 1.08; 9 trials), knee
      stability measured with KT-1000 arthrometer (MD -0.74 mm, 95% CI -1.10 to -0.37;
      5 trials, 363 participants) and rotational knee stability tested by the pivot
      shift test (normal or nearly normal categories: 293/298 versus 382/415; RR 1.06,
      95% CI 1.02 to 1.09; 9 trials). There were also statistically significant
      differences in favour of double-bundle reconstruction for newly occurring
      meniscal injury (9/240 versus 24/358; RR 0.46, 95% CI 0.23 to 0.92; 6 trials) and
      traumatic ACL rupture (1/120 versus 8/149; RR 0.17, 95% CI 0.03 to 0.96; 3
      trials). There were no statistically significant differences found between the
      two groups in range of motion (flexion and extension) deficits. AUTHORS'
      CONCLUSIONS: There is insufficient evidence to determine the relative
      effectiveness of double-bundle and single-bundle reconstruction for anterior
      cruciate ligament rupture in adults, although there is limited evidence that
      double-bundle ACL reconstruction has some superior results in objective
      measurements of knee stability and protection against repeat ACL rupture or a new
      meniscal injury. High quality, large and appropriately reported randomised
      controlled trials of double-bundle versus single-bundle reconstruction for
      anterior cruciate ligament rupture in adults appear justified.

PMID- 23152259
TI  - Omentoplasty for esophagogastrostomy after esophagectomy.
AB  - BACKGROUND: Esophagectomy followed by esophagogastrostomy is the preferred
      treatment for early-stage esophageal cancer. It carries the risk of anastomotic
      leakage after esophagogastric anastomosis, which is one of the most dangerous
      complications and causes considerable morbidity and mortality. Omentoplasty was
      recommended in some studies to preventing anastomotic leaks associated with
      esophagogastrostomy. However, the value of omentoplasty for esophagogastrostomy
      after esophagectomy has not been systematically reviewed. OBJECTIVES: To assess
      the effects of omentoplasty for esophagogastrostomy after esophagectomy in
      esophageal cancer patients. SEARCH METHODS: A comprehensive search strategy was
      carried out to identify eligible studies for inclusion in the Cochrane Central
      Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, PubMed and other
      reliable resources. SELECTION CRITERIA: Randomized controlled trials comparing
      omentoplasty with no omentoplasty for esophagogastrostomy after esophagectomy in
      esophageal cancer patients were eligible for inclusion. DATA COLLECTION AND
      ANALYSIS: Two review authors (Yong Yuan and Xiaoxi Zeng) independently assessed
      the quality of included studies and extracted data, with disagreements resolved
      by arbitration by another review author. Results of dichotomous outcomes were
      expressed as risk ratios (RR) with 95% confidence intervals (CI), while
      continuous outcomes were expressed as mean differences (MD) with 95% CI. Meta
      analysis was performed where the data available were sufficiently similar.
      Subgroup analysis was carried out based on different operation approaches. MAIN
      RESULTS: Two randomized controlled trials (449 participants) were included in the
      review. There was no significant difference for hospital mortality between the
      study (with omentoplasty) and the control group (without omentoplasty) (RR 1.00;
      95% CI 0.25 to 3.92). Neither of the included studies reported the difference of
      long-term survival between two groups. The incidence of postoperative anastomotic
      leakage was significantly lower in patients treated with omentoplasty than those
      without (RR 0.22; 95% CI 0.08 to 0.58); but the additional benefit only showed in
      patients receiving a transhiatal esophagogastrectomy (THE) procedure in subgroup
      analysis (THE: RR 0.23; 95% CI 0.07 to 0.79; transthoracic esophagogastrectomy
      (TTE): RR 0.19; 95% CI 0.03 to 1.03). Omentoplasty did not significantly improve
      other surgical-related complications, anastomotic strictures (RR 0.73; 95% CI
      0.21 to 2.58) and duration of hospitalization (MD -2.70; 95% CI -6.01 to 0.61).
      AUTHORS' CONCLUSIONS: Omentoplasty may provide an additional benefit to decrease
      the incidence of anastomotic leakage after esophagectomy and esophagogastrostomy
      for esophageal cancer patients without increasing or decreasing other
      complications, especially for those patients treated with THE. Further randomized
      controlled trials are still needed to investigate the influences of omentoplasty
      in different operation procedures of esophagectomy and esophagogastrostomy on the
      incidence of anastomotic leakage, anastomotic stricture, long-term survival rate
      and quality of life after esophagectomy and esophagogastrostomy.

PMID- 23152260
TI  - Vaccines for preventing rotavirus diarrhoea: vaccines in use.
AB  - BACKGROUND: Rotavirus results in more diarrhoea-related deaths in children less
      than five years of age than any other single agent in countries with high
      childhood mortality. It is also a common cause of diarrhoea-related hospital
      admissions in countries with low childhood mortality. Currently licensed
      rotavirus vaccines include a monovalent rotavirus vaccine (RV1; Rotarix,
      GlaxoSmithKline Biologicals) and a pentavalent rotavirus vaccine (RV5; RotaTeq,
      Merck & Co., Inc.). Lanzhou lamb rotavirus vaccine (LLR; Lanzhou Institute of
      Biomedical Products) is used in China only. OBJECTIVES: To evaluate rotavirus
      vaccines approved for use (RV1, RV5, and LLR) for preventing rotavirus diarrhoea.
      SEARCH METHODS: We searched MEDLINE (via PubMed) (1966 to May 2012), the Cochrane
      Infectious Diseases Group Specialized Register (10 May 2012), CENTRAL (published
      in The Cochrane Library 2012, Issue 5), EMBASE (1974 to 10 May 2012), LILACS
      (1982 to 10 May 2012), and BIOSIS (1926 to 10 May 2012). We also searched the
      ICTRP (10 May 2012), www.ClinicalTrials.gov (28 May 2012) and checked reference
      lists of identified studies. SELECTION CRITERIA: We selected randomized
      controlled trials (RCTs) in children comparing rotavirus vaccines approved for
      use with placebo, no intervention, or another vaccine. DATA COLLECTION AND
      ANALYSIS: Two authors independently assessed trial eligibility, extracted data,
      and assessed risk of bias. We combined dichotomous data using the risk ratio (RR)
      and 95% confidence intervals (CI). We stratified the analysis by child mortality,
      and used GRADE to evaluate evidence quality. MAIN RESULTS: Forty-one trials met
      the inclusion criteria and enrolled a total of 186,263 participants. Twenty-nine
      trials (101,671 participants) assessed RV1, and 12 trials (84,592 participants)
      evaluated RV5. We did not find any trials assessing LLR.RV1Children aged less
      than one year: In countries with low-mortality rates, RV1 prevents 86% of severe
      rotavirus diarrhoea cases (RR 0.14, 95% CI 0.07 to 0.26; 40,631 participants, six
      trials; high-quality evidence), and, based on one large multicentre trial in
      Latin America and Finland, probably prevents 40% of severe all-cause diarrhoea
      episodes (rate ratio 0.60, 95% CI 0.50 to 0.72; 17,867 participants, one trial;
      moderate-quality evidence). In countries with high-mortality rates, RV1 probably
      prevents 63% of severe rotavirus diarrhoea cases (RR 0.37, 95% CI 0.18 to 0.75;
      5414 participants, two trials; moderate-quality evidence), and, based on one
      trial in Malawi and South Africa, 34% of severe all-cause diarrhoea cases (RR
      0.66, 95% CI 0.44 to 0.98; 4939 participants, one trial; moderate-quality
      evidence).Children aged up to two years: In countries with low-mortality rates,
      RV1 prevents 85% of severe rotavirus diarrhoea cases (RR 0.15, 95% CI 0.12 to
      0.20; 32,854 participants, eight trials; high-quality evidence), and probably 37%
      of severe all-cause diarrhoea episodes (rate ratio 0.63, 95% CI 0.56 to 0.71;
      39,091 participants, two trials; moderate-quality evidence). In countries with
      high-mortality rates, based on one trial in Malawi and South Africa, RV1 probably
      prevents 42% of severe rotavirus diarrhoea cases (RR 0.58, 95% CI 0.42 to 0.79;
      2764 participants, one trial; moderate-quality evidence), and 18% of severe all
      cause diarrhoea cases (RR 0.82, 95% CI 0.71 to 0.95; 2764 participants, one
      trial; moderate-quality evidence).RV5Children aged less than one year: In
      countries with low-mortality rates, RV5 probably prevents 87% of severe rotavirus
      diarrhoea cases (RR 0.13, 95% CI 0.04 to 0.45; 2344 participants, three trials;
      moderate-quality evidence), and, based on one trial in Finland, may prevent 72%
      of severe all-cause diarrhoea cases (RR 0.28, 95% CI 0.16 to 0.48; 1029
      participants, one trial; low-quality evidence). In countries with high-mortality
      rates, RV5 prevents 57% of severe rotavirus diarrhoea (RR 0.43, 95% CI 0.29 to
      0.62; 5916 participants, two trials; high-quality evidence), but there was
      insufficient data to assess the effect on severe all-cause diarrhoea.Children
      aged up to two years: Four studies provided data for severe rotavirus and all
      cause diarrhoea in countries with low-mortality rates. Three trials reported on
      severe rotavirus diarrhoea cases and found that RV5 probably prevents 82% (RR
      0.18, 95% CI 0.07 to 0.50; 3190 participants, three trials; moderate-quality
      evidence), and another trial in Finland reported on severe all-cause diarrhoea
      cases and found that RV5 may prevent 96% (RR 0.04, 95% CI 0.00 to 0.70; 1029
      participants, one trial; low-quality evidence). In high-mortality countries, RV5
      prevents 41% of severe rotavirus diarrhoea cases (RR 0.59, 95% CI 0.43 to 0.82;
      5885 participants, two trials; high-quality evidence), and 15% of severe all
      cause diarrhoea cases (RR 0.85, 95% CI 0.75 to 0.98; 5977 participants, two
      trials; high-quality evidence).There was no evidence of a vaccine effect on
      mortality (181,009 participants, 34 trials; low-quality evidence), although the
      trials were not powered to detect an effect on this end point.Serious adverse
      events were reported in 4565 out of 99,438 children vaccinated with RV1 and in
      1884 out of 78,226 children vaccinated with RV5. Fifty-eight cases of
      intussusception were reported in 97,246 children after RV1 vaccination, and 34
      cases in 81,459 children after RV5 vaccination. No significant difference was
      found between children receiving RV1 or RV5 and placebo in the number of serious
      adverse events, and intussusception in particular. AUTHORS' CONCLUSIONS: RV1 and
      RV5 prevent episodes of rotavirus diarrhoea. The vaccine efficacy is lower in
      high-mortality countries; however, due to the higher burden of disease, the
      absolute benefit is higher in these settings. No increased risk of serious
      adverse events including intussusception was detected, but post-introduction
      surveillance studies are required to detect rare events associated with
      vaccination.

PMID- 23152261
TI  - Clomiphene citrate in combination with gonadotropins for controlled ovarian
      stimulation in women undergoing in vitro fertilization.
AB  - BACKGROUND: Gonadotropins are the most commonly used medication for controlled
      ovarian stimulation in in vitro fertilization (IVF). However, they are expensive,
      invasive and are associated with risk of ovarian hyperstimulation syndrome
      (OHSS). With recent calls for patient friendly IVF, there has been an interest in
      the use of clomiphene citrate with or without gonadotropins to reduce the burden
      of injections. However, it is not known whether regimens using clomiphene are at
      least as effective as gonadotropins alone. OBJECTIVES: To determine whether
      clomiphene citrate with gonadotropins (with or without mid-cycle antagonist) is
      more effective than gonadotropins with gonadotropin-releasing hormone (GnRH)
      agonists for controlled ovarian stimulation in IVF or intracytoplasmic sperm
      injection (ICSI) treatment. SEARCH METHODS: Cochrane Menstrual Disorders and
      Subfertility Group Trials Register (searched March 2012), Cochrane Central
      Register of Controlled Trials (CENTRAL) (The Cochrane Library 2012, first
      quarter), MEDLINE (1970 to March 2012), EMBASE (1985 to Mar 2012) and reference
      lists of articles. Relevant conference proceedings were handsearched. SELECTION
      CRITERIA: Randomised controlled trials (RCT) were included. Live birth rate (LBR)
      per woman was the primary outcome. DATA COLLECTION AND ANALYSIS: Two review
      authors independently assessed the eligibility and quality of trials MAIN
      RESULTS: Fourteen studies were included in the review. Meta-analysis could be
      performed with the data of 12 included studies, with a total of 2536
      participants. There was no evidence that clomiphene along with gonadotropins for
      IVF, with or without mid-cycle GnRH antagonist, differed from gonadotropins alone
      in GnRH agonist protocols in terms of live births (5 RCTs, 1079 women; OR 0.93,
      95% CI 0.69 to1.24) or clinical pregnancy (11 RCTs, 1864 women; OR 1.07, 95% CI
      0.85 to1.33). This means that for a typical clinic with 23% LBR using a GnRH
      agonist regimen, switching to clomiphene protocols would be expected to result in
      LBRs between 16% and 26%. There was a significant reduction in the incidence of
      OHSS (5 RCTs, 1559 women; OR 0.23, 95% CI 0.10 to 0.52). This means that for a
      typical clinic with 3.5% prevalence of OHSS using a GnRH agonist regimen,
      switching to clomiphene citrate protocols would be expected to reduce the
      incidence to between 0.8% and 1.8%. The trials included in this review were very
      old and outcomes such as live births, multiple pregnancy, OHSS and miscarriages
      have not been reported by most studies. AUTHORS' CONCLUSIONS: There was no
      evidence to indicate that clomiphene with gonadotropins (with or without GnRH
      antagonist) differed significantly from gonadotropins in GnRH agonist protocols
      for women undergoing IVF treatment, in terms of live births or pregnancy rates.
      Meanwhile, use of clomiphene led to a reduction in the incidence of OHSS.
      However, these results were based on data from a small number of underpowered
      randomised trials with few participants. Hence there was insufficient evidence to
      recommend use of clomiphene citrate in routine IVF practice. Larger trials with
      adequate power are required.

PMID- 23152263
TI  - Interventions for drooling in children with cerebral palsy.
AB  - BACKGROUND: Drooling is a common problem for children with cerebral palsy (CP).
      This can be distressing for these children as well as for their parents and
      caregivers. The consequences of drooling include risk of social rejection, damp
      and soiled clothing, unpleasant odour, irritated chapped skin, mouth infections,
      dehydration, interference with speech, damage to books, communication aids,
      computers, and the risk of social isolation (Blasco 1992; Van der Burg 2006). A
      range of interventions exist that aim to reduce or eliminate drooling. There is a
      lack of consensus regarding which interventions are most effective for children
      with CP. OBJECTIVES: (1) To evaluate the effectiveness and safety of
      interventions aimed at reducing or eliminating drooling in children with cerebral
      palsy. (2) To provide the best available evidence to inform clinical practice.
      (3) To assist with future research planning. SEARCH METHODS: We searched the
      following databases from inception to December 2010 : Cochrane Central Register
      of Controlled Trials (CENTRAL); Medline via Ovid; EMBASE; CINAHL; ERIC; Psych
      INFO; Web of Science; Web of Knowledge; AMED; SCOPUS; Dissertation Abstracts.We
      searched for ongoing clinical trials in the Clinical Trials web site
      (http://clinicaltrials.gov.) and in the Current Controlled Trials web site
      (http://www.controlled-trials.com/). We hand searched a range of relevant
      journals and conference proceeding abstracts. SELECTION CRITERIA: Only randomised
      controlled trials (RCTs) and controlled clinical trials (CCTs) were included.
      DATA COLLECTION AND ANALYSIS: Data were extracted independently by MW, MS and LP
      and differences resolved through discussion. MAIN RESULTS: Six studies were
      eligible for inclusion in the review. Four of these studies were trials using
      botulinum toxin-A (BoNT-A) and two were trials on the pharmacological
      interventions, benztropine and glycopyrrolate. No RCTs or CCTs were retrieved on
      surgery, physical, oro-motor and oro-sensory therapies, behavioural
      interventions, intra-oral appliances or acupuncture. In the studies eligible for
      review, there was considerable heterogeneity within and across interventions and
      a meta-analysis was not possible. A descriptive summary of each study is
      provided. All studies showed some statistically significant change for treatment
      groups up to 1 month post intervention. However, there were methodological flaws
      associated with all six studies. AUTHORS' CONCLUSIONS: It was not possible to
      reach a conclusion on the effectiveness and safety of either BoNT-A or the
      pharmaceutical interventions, benztropine and glycopyrrolate. There is
      insufficient evidence to inform clinical practice on interventions for drooling
      in children with CP. Directions for future research are provided.

PMID- 23152264
TI  - Febuxostat for treating chronic gout.
AB  - BACKGROUND: Gout is the most common inflammatory arthritis in men over 40 years
      and has an increasing prevalence among postmenopausal women. Lowering serum uric
      acid levels remains one of the primary goals in the treatment of chronic gout. In
      clinical trials, febuxostat has been shown to be effective in lowering serum uric
      acid levels to < 6.0 mg/dL. OBJECTIVES: To evaluate the benefits and harms of
      febuxostat for chronic gout. SEARCH METHODS: We searched The Cochrane Library,
      MEDLINE, EMBASE, and International Pharmaceutical Abstracts from inception to
      July 2011. The ClinicalTrials.gov website was searched for references to trials
      of febuxostat. Our search did not include any restrictions. SELECTION CRITERIA:
      Two authors independently reviewed the search results and disagreements were
      resolved by discussion. We included any controlled clinical trial or open label
      trial (OLT) using febuxostat at any dose. DATA COLLECTION AND ANALYSIS: Data and
      risk of bias were independently extracted by two authors and summarised in a meta
      analysis. Continuous data were expressed as mean difference and dichotomous data
      as risk ratio (RR). MAIN RESULTS: Four randomised trials and two OLTs with 3978
      patients were included. Risk of bias differed by outcome, ranging from low to
      high risk of bias. Included studies failed to report on five to six of the nine
      outcome measures recommended by OMERACT. Patients taking febuxostat 120 mg and
      240 mg reported more frequent gout flares than in the placebo group at 4 to 28
      weeks (RR 1.7; 95% CI 1.3 to 2.3, and RR 2.6; 95% CI 1.8 to 3.7 respectively). No
      statistically significant differences were observed at 40 mg and 80 mg. Compared
      to placebo, patients on febuxostat 40 mg were 40.1 times more likely to achieve
      serum uric acid levels < 6.0 mg/dL at 4 weeks (95% CI 2.5 to 639), with an
      absolute treatment benefit of 56% (95% CI 37% to 71%). For febuxostat 80 mg and
      120 mg, patients were 68.9 and 80.7 times more likely to achieve serum uric acid
      levels < 6.0 mg/dL at their final visit compared to placebo (95% CI 13.8 to
      343.9, 95% CI 16.0 to 405.5), respectively; with an absolute treatment benefit of
      75% and 87% (95% CI 68 to 80% and 81 to 91%), respectively. Total discontinuation
      rates were significantly higher in the febuxostat 80 mg group compared to placebo
      (RR 1.4; 95% CI 1.0 to 2.0, absolute risk increase 11%; 95% CI 3 to 19%). No
      other differences were observed.When comparing allopurinol to febuxostat at 24 to
      52 weeks, the number of gout flares was not significantly different between the
      two groups, except for febuxostat 240 mg (RR 2.3; 95% CI 1.7 to 3.0). Patients on
      febuxostat 40 mg showed no statistically significant differences in benefits or
      harms. Patients on febuxostat 80 mg and 120 mg were 1.8 and 2.2 times more likely
      to achieve serum uric acid levels < 6.0 mg/dL at their final visit (95% CI 1.6 to
      2.2, 95% CI 1.9 to 2.5) with an absolute treatment benefit of 29% and 44% (95% CI
      25% to 33%, 95% CI 38% to 50%), respectively, at 24 to 52 weeks. Total
      discontinuation rates were higher for febuxostat 80 mg and 120 mg compared to
      allopurinol (RR 1.5; 95% CI 1.2 to 1.8, absolute risk increase 11%; 95% CI 6% to
      16%; and RR 2.6; 95% CI 2.0 to 3.3, absolute risk increase 20%; 95% CI 3% to 14%,
      respectively). Discontinuations due to adverse events were similar across groups.
      Total adverse events were lower for febuxostat 80 mg and 120 mg compared with
      allopurinol (RR 0.93; 95% CI 0.87 to 0.99, absolute risk increase 6%; 95% CI 0.7%
      to 11%; and RR 0.90; 95% CI 0.84 to 0.96, absolute risk increase 8%; 95% CI 3% to
      13%, respectively). No other relevant differences were noted.After 3 years of
      follow-up there were no statistically significant differences regarding
      effectiveness and harms between febuxostat 80 mg or 120 mg and allopurinol groups
      (adverse event rate per 100 patient-years 227, 216, and 246, respectively).
      AUTHORS' CONCLUSIONS: Although the incidence of gout flares requiring treatment
      may be increased in patients taking febuxostat compared to placebo or allopurinol
      during early treatment, no such increase in gout flares was observed in the long
      term follow-up study when compared to allopurinol. Febuxostat at any dose was
      shown to be beneficial in achieving serum uric acid levels < 6.0 mg/dL and
      reducing serum uric acid levels in the period from baseline to final visit when
      compared to placebo and to allopurinol. However, the grade of evidence ranged
      from low to high, which indicates that further research is needed.

PMID- 23152262
TI  - Interventions for increasing fruit and vegetable consumption in children aged 5
      years and under.
AB  - BACKGROUND: Insufficient consumption of fruits and vegetables in childhood
      increases the risk of future chronic diseases including cardiovascular disease.
      OBJECTIVES: To assess the effectiveness, cost-effectiveness and associated
      adverse events of interventions designed to increase the consumption of fruit
      and/or vegetables amongst children aged five years and under. SEARCH METHODS: The
      Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library
      Issue 2, 2010, MEDLINE (1950 to 2010 April week 4), EMBASE (1947 to 2010 week
      18), CINAHL (up to 12 May 2010), PsycINFO (up to 12 May 2010) and Proquest
      Dissertations and Theses (up to February 2011) were searched to identify eligible
      trials, as well as electronic trial registers (also up to February 2011). The
      reference lists of included trials were reviewed and handsearches of three
      international nutrition journals were also performed. Authors of all included
      trials were contacted in order to identify further potentially relevant trials.
      SELECTION CRITERIA: We included randomised controlled trials (RCTs), including
      cluster-randomised controlled trials, of any intervention primarily targeting
      fruit and/or vegetable consumption among children aged five years and under and
      incorporating a biochemical or dietary assessment of fruit and/or vegetable
      consumption. Two review authors independently screened the titles and abstracts
      of identified papers. A third review author with expertise in review methodology
      resolved any disagreements regarding study eligibility. DATA COLLECTION AND
      ANALYSIS: Two review authors independently extracted data and assessed the risk
      of bias of the included studies. A third reviewer resolved disagreements between
      review authors. Fixed-effect models were used to perform meta-analysis for the
      primary review outcomes where a sufficient number of trials with suitable data
      and homogeneity were identified. MAIN RESULTS: Five trials, with 13 trial arms
      and 3967 participants were included in the review. Two trials examined the impact
      of specific feeding practices (e.g. repeated food exposure) in increasing child
      intake of a target vegetable. Two trials assessed the effectiveness of home
      visiting programs implemented in disadvantaged communities and one trial
      investigated the effect of a preschool-based intervention in increasing child
      fruit and vegetable intake. Risk of bias of included studies was low although
      three of the five trials were judged to be at high risk of performance bias. Meta
      analysis of two trials examining repeated food exposure versus a no intervention
      comparison found no significant difference in target vegetable consumption in the
      short term (mean difference (MD) 1.37, 95% confidence interval (CI) -2.78 to
      5.52). Coupling repeated food exposure with a tangible non-food or social reward,
      was effective in increasing targeted vegetable consumption in the short term
      based on one trial. Home visiting programs provided to disadvantaged groups did
      not significantly increase overall fruit intake in the short term (standardised
      mean difference (SMD) 0.01, 95% CI -0.09 to 0.11). Similarly, a multi-component
      preschool-based intervention failed to significantly increase child consumption
      of vegetables, but did report a small significant increase in mean child
      consumption of fruit, six months following baseline assessment. None of the
      trials investigated intervention cost-effectiveness or reported information
      regarding any adverse events or unintended adverse consequences of the
      intervention. AUTHORS' CONCLUSIONS: Despite the importance of encouraging fruit
      and vegetable consumption among children aged five years and under, this review
      identified few randomised controlled trials investigating interventions to
      achieve this.

PMID- 23152265
TI  - Pre-operative nutrition support in patients undergoing gastrointestinal surgery.
AB  - BACKGROUND: Post-operative management in gastrointestinal (GI) surgery is
      becoming well established with 'Enhanced Recovery After Surgery' protocols
      starting 24 hours prior to surgery with carbohydrate loading and early oral or
      enteral feeding given to patients the first day following surgery. However,
      whether or not nutritional intervention should be initiated earlier in the
      preoperative period remains unclear. Poor pre-operative nutritional status has
      been linked consistently to an increase in post-operative complications and
      poorer surgical outcome. OBJECTIVES: To review the literature on preoperative
      nutritional support in patients undergoing gastrointestinal surgery (GI). SEARCH
      METHODS: The searches were initially run in March 2011 and subsequently updated
      in February 2012. Databases including all EBM Reviews (Cochrane DSR, ACP Journal
      Club, DARE, CCTR, CMR, HTA and NHSEED) MEDLINE, EMBASE, AMED, British Nursing
      Index Archive using OvidSP were included and a search was run on each database
      separately after which duplicates were excluded. SELECTION CRITERIA: The
      inclusion criteria were randomised controlled trials that evaluated pre-operative
      nutritional support in GI surgical participants using a nutritional formula
      delivered by a parenteral, enteral or oral route. The primary outcomes included
      post-operative complications and length of hospital stay. DATA COLLECTION AND
      ANALYSIS: Two observers screened the abstracts for inclusion in the review and
      performed data extraction. Bias was assessed for each of the included studies
      using the bias assessment tables in the Cochrane Software Review Manager (version
      5.1, Cochrane Collaboration). The trials were analysed using risk ratios with
      Mantel-Haenszel in fixed effects methods displayed with heterogeneity. Meta
      analyses were undertaken on trials evaluating immune enhancing (IE) nutrition,
      standard oral supplements, enteral and parenteral nutrition (PN) which were
      administered pre-operatively.Study characteristics were summarised in tables.
      Dichotomous and ratio data were entered into meta-analyses for the primary
      outcomes. These were then summarised in tables with assumed and corresponding
      risk with relative effect giving 95% confidence intervals. MAIN RESULTS: The
      searches identified 9900 titles and, after excluding duplicates, 6433 titles were
      initially screened. After the initial title screen, 6266 were excluded. Abstracts
      were screened for 167 studies and 33 articles were identified as meeting the
      inclusion criteria, of which 13 were included in the review after an assessment
      of the complete manuscripts.Seven trials evaluating IE nutrition were included in
      the review, of which 6 were combined in a meta-analysis. These studies showed a
      low to moderate level of heterogeneity and significantly reduced total post
      operative complications (risk ratio (RR) 0.67 CI 0.53 to 0.84). Three trials
      evaluating PN were included in a meta-analysis and a significant reduction in
      post-operative complications was demonstrated (RR 0.64 95% CI 0.46 to 0.87) with
      low heterogeneity, in predominantly malnourished participants. Two trials
      evaluating enteral nutrition (RR 0.79, 95% CI 0.56 to 1.10) and 3 trials
      evaluating standard oral supplements (RR 1.01 95% CI 0.56 to 1.10) were included,
      neither of which showed any difference in the primary outcomes. AUTHORS'
      CONCLUSIONS: There have been significant benefits demonstrated with pre-operative
      administration of IE nutrition in some high quality trials. However, bias was
      identified which may limit the generalizability of these results to all GI
      surgical candidates and the data needs to be placed in context with other recent
      innovations in surgical management (eg-ERAS). Some unwanted effects have also
      been reported with components of IE nutrition in critical care patients and it is
      unknown whether there would be detrimental effects by administering IE nutrition
      to patients who could require critical care support after their surgery. The
      studies evaluating PN demonstrated that the provision of PN to predominantly
      malnourished surgical candidates reduced post-operative complications; however,
      these data may not be applicable to current clinical practice, not least because
      they have involved a high degree of 'hyperalimentation'. Trials evaluating
      enteral or oral nutrition were inconclusive and further studies are required to
      select GI surgical patients for these nutritional interventions.

PMID- 23152266
TI  - Psychological therapies for pathological and problem gambling.
AB  - BACKGROUND: Various psychological therapies for pathological and problem gambling
      have been evaluated in randomised trials. A synthesis of best-quality evidence is
      required. OBJECTIVES: The objective was to synthesise evidence from randomised
      trials of psychological therapies for pathological and problem gambling
      (cognitive-behaviour therapy (CBT), motivational interviewing therapy,
      integrative therapy, other psychological therapy), in order to indicate the
      efficacy of therapies and durability of therapy effects, relative to control
      conditions. SEARCH METHODS: We conducted a search of the Cochrane Depression,
      Anxiety and Neurosis Review Group's Specialised Register (CCDANCTR), which
      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 carried
      out complementary searches of MEDLINE, EMBASE, PsycINFO, LILACS and CENTRAL for
      studies published between January 1980 and October 2011. We examined the WHO
      International Clinical Trials Registry Platform and ClinicalTrials.gov and also
      conducted manual searches of selected journals and reference lists of included
      studies. SELECTION CRITERIA: Included studies were clinical trials using random
      allocation to groups, considering pathological or problem gamblers, and
      evaluating a psychological therapy for pathological or problem gambling. Control
      conditions included 'no treatment' controls, referral to Gamblers Anonymous and
      non-specific treatment component controls. DATA COLLECTION AND ANALYSIS: We
      systematically extracted data on the characteristics and results of studies.
      Primary outcomes were measures of gambling symptom severity, financial loss from
      gambling and frequency of gambling. Secondary outcomes were occurrence of
      pathological gambling diagnoses and depression and anxiety symptoms. Treatment
      effects were defined by comparisons between therapy and control conditions at
      post-treatment assessments (conducted from 0 to 3 months following completion of
      treatment) and follow-up assessments (conducted from 9 to 12 months following
      completion of treatment), respectively, using the standardised mean difference
      (SMD) or risk ratio (RR). We synthesised results through random-effects meta
      analysis. MAIN RESULTS: Fourteen studies (n = 1245) met the inclusion criteria.
      Eleven studies compared CBT with control and comparisons at 0 to 3 months post
      treatment showed beneficial effects of therapy that ranged from medium (when
      defined by financial loss from gambling: SMD -0.52; 95% confidence interval (CI) 
      0.71 to -0.33, n = 505) to very large (for gambling symptom severity: SMD -1.82;
      95% CI -2.61 to -1.02, n = 402). Only one study (n = 147) compared groups at 9 to
      12 months follow-up and produced smaller effects that were not significant. Four
      studies of motivational interviewing therapy were identified and mainly
      considered samples demonstrating less severe gambling (relative to studies of
      pathological gamblers). Data suggested reduced financial loss from gambling
      following motivational interviewing therapy at 0 to 3 months post-treatment (SMD 
      0.41; 95% CI -0.75 to -0.07, n = 244), although comparisons on other outcomes
      were not significant. The effect approached zero when defined by gambling symptom
      severity (SMD -0.03; 95% CI -0.55 to 0.50, n = 163). Studies compared groups at 9
      to 12 months follow-up and found a significant effect of motivational
      interviewing therapy in terms of frequency of gambling (SMD -0.53; 95% CI -1.04
      to -0.02, n = 62), with comparisons on other outcomes that were not significant.
      Two studies of integrative therapies also considered samples demonstrating
      overall low gambling severity, and found no significant effects of therapy at 0
      to 3 months post-treatment. Comparisons at 9 to 12 months follow-up suggested a
      medium effect from therapy in terms of gambling symptom severity, with no
      significant differences for other outcomes. One study (n = 18) considered another
      psychological therapy (i.e.Twelve-Step Facilitated Group Therapy) and suggested
      beneficial effects in terms of most outcomes at 0 to 3 months post-treatment. The
      evidence supporting these various classes of therapy ranged from very low to low
      quality. AUTHORS' CONCLUSIONS: This review supports the efficacy of CBT in
      reducing gambling behaviour and other symptoms of pathological and problem
      gambling immediately following therapy. However, the durability of therapeutic
      gain is unknown. There is preliminary evidence for some benefits from
      motivational interviewing therapy in terms of reduced gambling behaviour,
      although not necessarily other symptoms of pathological and problem gambling.
      However, the findings are based on few studies and additional research is needed
      to inform conclusions. There is also evidence suggestive of some possible benefit
      from integrative therapies, and other psychological therapies for pathological
      and problem gambling. However, there are too few studies and evidence is
      insufficient to evaluate these therapies. The majority of studies in this review
      varied in risk of bias, and much of the evidence comes from studies with multiple
      limitations. The current data may thus reflect overestimates of treatment
      efficacy.

PMID- 23152267
TI  - Pharmacological interventions for treating heart failure in patients with chagas
      cardiomyopathy.
AB  - BACKGROUND: Chagas disease-related cardiomyopathy is a major cause of morbidity
      and mortality in Latin America. Despite the substantial burden to the healthcare
      system, there is uncertainty regarding the efficacy and safety of pharmacological
      interventions for treating heart failure in patients with Chagas disease.
      OBJECTIVES: To assess the benefits and harms of current pharmacological
      interventions for treating heart failure in patients with Chagas cardiomyopathy.
      SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials
      (CENTRAL, The Cochrane Library) Issue 1, 2011, MEDLINE (Ovid), EMBASE (Ovid),
      LILACS and ISI Web of Science to April 2011. We checked the reference lists of
      included papers. No language restrictions were applied. SELECTION CRITERIA: We
      included randomized clinical trials assessing the effects of pharmacological
      interventions for treating heart failure in adult patients (>=18 years) with
      symptomatic heart failure (New York Heart Association class II to IV),
      irrespective of the left ventricular ejection fraction stage, reduced or
      preserved, with Chagas cardiomyopathy. No limits were applied with respect to the
      follow-up duration. Primary outcomes were all-cause mortality, cardiovascular
      mortality at 30 days, time to heart decompensation and disease-free period (at
      30, 60 and 90 days), and adverse events. DATA COLLECTION AND ANALYSIS: Two
      authors independently performed study selection, risk of bias assessment and data
      extraction. We estimated relative risks (RR) and the respective 95% confidence
      intervals (CIs) for dichotomous outcomes. We measured statistical heterogeneity
      using the I(2) statistic. We used a fixed-effect model to synthesize the
      findings. We contacted authors for additional data. MAIN RESULTS: We included two
      randomized clinical trials involving 69 participants. Both trials compared
      carvedilol against placebo, and had a high risk of bias. Carvedilol compared with
      placebo did not significantly affect all-cause mortality (2/34 (5.88%) versus
      3/35 (5.87%); pooled RR 0.69, 95% CI 0.12 to 3.88, I(2) = 0%). None of the trials
      reported on cardiovascular mortality, time to heart decompensation or disease
      free period. Evidence on the adverse effects of carvedilol is inconclusive.
      AUTHORS' CONCLUSIONS: This Cochrane review has found a lack of evidence on the
      effects of carvedilol for treating heart failure in patients with Chagas disease.
      The two included trials were underpowered and had a high risk of bias. There are
      no conclusive data to support the use of carvedilol for treating Chagas
      cardiomyopathy. Unless randomized clinical trials provide evidence of a treatment
      effect, and the trade off between potential benefits and harms is established,
      policy-makers, clinicians, and academics should be cautious when recommending and
      administering carvedilol for treating heart failure in patients with Chagas
      disease. The efficacy and safety of other pharmacological interventions for
      treating heart failure in patients with Chagas disease is unknown.

PMID- 23152268
TI  - Antibiotics for uncomplicated diverticulitis.
AB  - BACKGROUND: Diverticulitis is an inflammatory complication to the very common
      condition diverticulosis. Uncomplicated diverticulitis has traditionally been
      treated with antibiotics with reference to the microbiology, extrapolation from
      trials on complicated intra-abdominal infections and clinical experience.
      OBJECTIVES: To assess the effects of antibiotic interventions for uncomplicated
      diverticulitis on relevant outcome. SEARCH METHODS: Studies were identified by
      computerised searches of the The Cochrane Library (CENTRAL), MEDLINE and EMBASE.
      Ongoing trials were identified and reference lists of identified trials and
      relevant review articles were screened for additional studies. SELECTION
      CRITERIA: RCTs including all types of patients with a radiological confirmed
      diagnosis of left-sided uncomplicated diverticulitis. Interventions of
      antibiotics compared to any other antibiotic treatment (different regime, route
      of administration, dosage or duration of treatment), placebo or no antibiotics.
      Outcome measures were complications, emergency surgery, recurrence, late
      complications and duration of hospital stay and recovery of signs of infection.
      DATA COLLECTION AND ANALYSIS: Two authors performed the searches, identification
      of RCTs, trial assessment and data extraction. Disagreements were resolved by
      discussion or involvement of a third part. Authors of trials were contacted to
      obtain additional data if needed or were contacted for preliminary results of
      ongoing trials. Effect estimates were extracted as relative risks (RR). MAIN
      RESULTS: Three RCTs were identified. A qualitative approach with no meta analysis
      was performed because of variety in interventions between included studies.
      Interventions compared were antibiotics to no antibiotics, single to double
      compound antibiotic therapy and short to long IV administration. None of the
      studies found significant difference between the tested interventions. Risk of
      bias varied from low to high. The newest RCT overall had the best quality and
      statistical power. AUTHORS' CONCLUSIONS: The newest evidence from one RCT says
      there is no significant difference between antibiotics versus no antibiotics in
      the treatment of uncomplicated diverticulitis. Previous RCTs have only suggested
      a non-inferiority between different antibiotic regimes and treatment lengths.
      This new evidence needs confirmation from more RCTs before it can be implicated
      safely in clinical guidelines. Ongoing RCTs will be published in the years to
      come and more are needed. The role of antibiotics in the treatment of complicated
      diverticulitis has not been investigated yet.

PMID- 23152269
TI  - Routine neonatal circumcision for the prevention of urinary tract infections in
      infancy.
AB  - BACKGROUND: Neonatal circumcision is a fairly common surgical procedure that may
      be carried out for medical reasons, one of them being prevention of urinary tract
      infections (UTI) in male infants. Circumcision could help in reducing the
      incidence of UTI by reducing periurethral bacterial colonization, which is
      accepted as a potential risk factor in UTI. Evidence is needed to inform the
      benefits or harm for the routine use of this intervention. OBJECTIVES: To assess
      the effectiveness and safety of routine neonatal circumcision for the prevention
      of UTIs in infancy. SEARCH METHODS: We searched the Cochrane Neonatal Review
      Group Trials Register comprising references identified from comprehensive
      electronic database searches and handsearches of relevant journals and abstract
      books of conference proceedings. We completed this search 30 June 2011. SELECTION
      CRITERIA: Randomised controlled trials and quasi-randomised controlled trials.
      DATA COLLECTION AND ANALYSIS: Two review authors had planned to independently
      screen studies, extract data and assess risk of bias using standard Cochrane
      Collaboration methodologies. We did not identify any studies for inclusion in
      this review. MAIN RESULTS: We did not identify any relevant studies after a
      comprehensive search of the literature. AUTHORS' CONCLUSIONS: We were unable to
      identify any randomised controlled trials on the use of routine neonatal
      circumcision for prevention of UTI in male infants. Until further evidence
      becomes available, clinicians should continue to base their decisions on position
      statements and recommendations and in conjunction with the opinions of the
      children's parents.

PMID- 23152270
TI  - Psychosocial interventions to reduce alcohol consumption in concurrent problem
      alcohol and illicit drug users.
AB  - BACKGROUND: Problem alcohol use is common among illicit drug users and is
      associated with adverse health outcomes. It is also an important factor in poor
      prognosis among drug users with hepatitis C virus (HCV) as it impacts on
      progression to hepatic cirrhosis or opiate overdose in opioid users. OBJECTIVES:
      To assess the effects of psychosocial interventions for problem alcohol use in
      illicit drug users (principally problem drug users of opiates and stimulants).
      SEARCH METHODS: We searched the Cochrane Drugs and Alcohol Group trials register
      (November 2011), the Cochrane Central Register of Controlled Trials (CENTRAL)
      (The Cochrane Library, Issue 11, November 2011), PUBMED (1966 to 2011); EMBASE
      (1974 to 2011); CINAHL (1982 to 2011); PsycINFO (1872 to 2011) and reference list
      of articles. We also searched: 1) conference proceedings (online archives only)
      of the Society for the Study of Addiction (SSA), International Harm Reduction
      Association (IHRA), International Conference on Alcohol Harm Reduction (ICAHR),
      and American Association for the Treatment of Opioid Dependence (AATOD); 2)
      online registers of clinical trials, Current Controlled Trials (CCT), Clinical
      Trials.org, Center Watch and International Clinical Trials Registry Platform
      (ICTRP). SELECTION CRITERIA: Randomised controlled trials comparing psychosocial
      interventions with another therapy (other psychosocial treatment, including non
      pharmacological therapies or placebo) in adult (over the age of 18 years) illicit
      drug users with concurrent problem alcohol use. DATA COLLECTION AND ANALYSIS: Two
      review authors independently assessed risk of bias and extracted data from
      included trials. MAIN RESULTS: Four studies, 594 participants, were included.
      Half of the trials were rated as having high or unclear risk of bias. They
      considered six different psychosocial interventions grouped into four
      comparisons: (1) cognitive-behavioural coping skills training versus 12-step
      facilitation (N = 41), (2) brief intervention versus treatment as usual (N =
      110), (3) hepatitis health promotion versus motivational interviewing (N = 256),
      and (4) brief motivational intervention versus assessment-only group (N = 187).
      Differences between studies precluded any pooling of data. Findings are described
      for each trial individually:comparison 1: no significant difference; comparison
      2: higher rates of decreased alcohol use at three months (risk ratio (RR) 0.32;
      95% confidence interval (CI) 0.19 to 0.54) and nine months (RR 0.16; 95% CI 0.08
      to 0.33) in the treatment as usual group; comparison 3 (group and individual
      format): no significant difference; comparison 4: more people reduced alcohol use
      (by seven or more days in the past 30 days at 6 months) in the brief motivational
      intervention compared to controls (RR 1.67; 95% CI 1.08 to 2.60). AUTHORS'
      CONCLUSIONS: Very little evidence exists that there is no difference in the
      effectiveness between different types of interventions and that brief
      interventions are not superior to assessment only or treatment as usual. No
      conclusion can be made because of the paucity of the data and the low quality of
      the retrieved studies.

PMID- 23152271
TI  - Interventions for preventing recurrent urinary tract infection during pregnancy.
AB  - BACKGROUND: Recurrent urinary tract infections (RUTI) are common in women who are
      pregnant and may cause serious adverse pregnancy outcomes for both mother and
      child including preterm birth and small-for-gestational-age babies. Interventions
      used to prevent RUTI in women who are pregnant can be pharmacological
      (antibiotics) or non-pharmacological (cranberry products, acupuncture, probiotics
      and behavioural modifications). So far little is known about the best way to
      prevent RUTI in pregnant women. OBJECTIVES: To assess the effects of
      interventions for preventing recurrent urinary tract infections in pregnant
      women.The primary maternal outcomes were RUTI before birth (variously defined)
      and preterm birth (before 37 weeks). The primary infant outcomes were small-for
      gestational age and total mortality. SEARCH METHODS: We searched the Cochrane
      Pregnancy and Childbirth Group's Trials Register (8 June 2012) and reference
      lists of retrieved articles. SELECTION CRITERIA: Published, unpublished and
      ongoing randomised controlled trials (RCTs), quasi-RCTs, clustered-randomised
      trials and abstracts of any intervention (pharmacological and non
      pharmacological) for preventing RUTI during pregnancy (compared with another
      intervention, placebo or with usual care). DATA COLLECTION AND ANALYSIS: Two
      review authors independently evaluated the one identified trial for inclusion and
      assessed trial quality. Two review authors extracted data. Data were checked for
      accuracy. MAIN RESULTS: The review included one trial involving 200 women. The
      trial compared a daily dose of nitrofurantoin and close surveillance (regular
      clinic visit, urine cultures and antibiotics when a positive culture was found)
      with close surveillance only. No significant differences were found for the
      primary outcomes: recurrent pyelonephritis (risk ratio (RR) 0.89, 95% confidence
      interval (CI) 0.31 to 2.53, one study, 167 women), recurrent urinary tract
      infection before birth (RR 0.30, 95% CI 0.06 to 1.38; one study 167 women) and
      preterm birth (before 37 weeks) (RR 1.18, 95% CI 0.42 to 3.35; one study 147
      women). The incidence of asymptomatic bacteriuria (ASB) (at least 10(3) colonies
      per mL) (secondary outcome), only reported in women with a clinic attendance rate
      of more than 90% (RR 0.55, 95% CI 0.34 to 0.89; one study, 102 women), was
      significantly reduced in women who received nitrofurantoin and close
      surveillance. AUTHORS' CONCLUSIONS: A daily dose of nitrofurantoin and close
      surveillance has not been shown to prevent RUTI compared with close surveillance
      alone. A significant reduction of ASB was found in women with a high clinic
      attendance rate and who received nitrofurantoin and close surveillance. There was
      limited reporting of both primary and secondary outcomes for both women and
      infants. No conclusions can be drawn regarding the optimal intervention to
      prevent RUTI in women who are pregnant. Randomised controlled trials comparing
      different pharmacological and non-pharmacological interventions are necessary to
      investigate potentially effective interventions to prevent RUTI in women who are
      pregnant.

PMID- 23152273
TI  - Ketamine for management of acute exacerbations of asthma in children.
AB  - BACKGROUND: Asthma is the most common chronic disease in children, and children
      with asthma frequently visit the paediatric emergency departments with acute
      exacerbations. Some of these children fail to respond to standard therapy
      (aerosol beta(2)-agonist with or without aerosol anticholinergic and oral or
      parenteral corticosteroids) for acute asthma leading to prolonged emergency
      department stay, hospitalisation, morbidity (e.g. barotrauma, intubation) and
      death, albeit rarely. Ketamine may relieve bronchospasm and is a potentially
      promising therapy for children with acute asthma who fail to respond to standard
      treatment. OBJECTIVES: To evaluate the efficacy of ketamine compared to placebo,
      no intervention or standard care for management of severe acute asthma in
      children who had not responded to standard therapy. SEARCH METHODS: We identified
      trials from the Cochrane Airways Group Specialised Register of trials (CAGR) and
      ClinicalTrials.gov. We reviewed reference lists of all primary studies and review
      articles for additional references. We contacted authors of identified trials and
      asked them to identify other published and unpublished studies. The latest search
      was in July 2012. SELECTION CRITERIA: Randomised controlled trials comparing
      ketamine to placebo or standard care in children (up to 18 years of age)
      presenting with an acute asthma exacerbation who had not responded to standard
      therapy. DATA COLLECTION AND ANALYSIS: Two review authors independently selected
      studies. The data were extracted in pre-defined proforma and were analysed
      independently by two review authors. The data analysis was performed using Review
      Manager 5.1. MAIN RESULTS: A single study enrolling 68 non-intubated children was
      found eligible for inclusion in review. The study had low or unclear risk of
      bias. It demonstrated no significant difference in respiratory rate, oxygen
      saturation, hospital admission rate (odds ratio (OR) 0.77; 95% confidence
      interval (CI) 0.23 to 2.58) and need for mechanical ventilation between ketamine
      (0.2 mg/kg intravenous bolus over one to two minutes, followed by a 0.5 mg/kg per
      hour continuous infusion for two hours) and placebo group. There were no
      significant side effects of ketamine in the study. There was also no difference
      in need for other adjuvant therapy (OR 2.19; 95% CI 0.19 to 25.40) and in
      Pulmonary Index Score (mean difference (MD) -0.40; 95% CI -1.21 to 0.41) between
      the groups. AUTHORS' CONCLUSIONS: The single study on non-intubated children with
      severe acute asthma did not show significant benefit and does not support the
      case studies and observational reports showing benefits of ketamine in both non
      ventilated and ventilated children. There were no significant side effects of
      ketamine. We could not find any trials on ventilated children. To prove that
      ketamine is an effective treatment for acute asthma in children, there is need
      for sufficiently powered randomised trials of high methodological quality with
      objective outcome measures of clinical importance. Future trials should also
      explore different doses of ketamine and its role in children needing ventilation
      because of severe acute asthma.

PMID- 23152272
TI  - Selective serotonin reuptake inhibitors (SSRIs) for stroke recovery.
AB  - BACKGROUND: Stroke is the major cause of adult disability. Selective serotonin
      reuptake inhibitors (SSRIs) have been used for many years to manage depression.
      Recently, small trials have demonstrated that SSRIs might improve recovery after
      stroke, even in people who are not depressed. Systematic reviews and meta
      analyses are the least biased way to bring together data from several trials.
      Given the promising effect of SSRIs on stroke recovery seen in small trials, a
      systematic review and meta-analysis is needed. OBJECTIVES: To determine whether
      SSRIs improve recovery after stroke, and whether treatment with SSRIs was
      associated with adverse effects. SEARCH METHODS: We searched the Cochrane Stroke
      Group Trials Register (August 2011), Cochrane Depression Anxiety and Neurosis
      Group Trials Register (November 2011), Cochrane Central Register of Controlled
      Trials (CENTRAL) (The Cochrane Library 2011, Issue 8), MEDLINE (from 1948 to
      August 2011), EMBASE (from 1980 to August 2011), CINAHL (from 1982 to August
      2011), AMED (Allied and Complementary Medicine) (from 1985 to August 2011),
      PsycINFO (from 1967 to August 2011) and PsycBITE (Pyschological Database for
      Brain Impairment Treatment Efficacy) (March 2012). To identify further published,
      unpublished and ongoing trials we searched trials registers, pharmaceutical
      websites, reference lists, contacted experts and performed citation tracking of
      included studies. SELECTION CRITERIA: We included randomised controlled trials
      that recruited stroke survivors (ischaemic or haemorrhagic) at any time within
      the first year. The intervention was any SSRI, given at any dose, for any period.
      We excluded drugs with mixed pharmacological effects. The comparator was usual
      care or placebo. In order to be included, trials had to collect data on at least
      one of our primary (dependence and disability) or secondary (impairments,
      depression, anxiety, quality of life, fatigue, healthcare cost, death, adverse
      events and leaving the trial early) outcomes. DATA COLLECTION AND ANALYSIS: We
      extracted data on demographics, type of stroke, time since stroke, our primary
      and secondary outcomes, and sources of bias. For trials in English, two review
      authors independently extracted data. For Chinese papers, one review author
      extracted data. We used standardised mean differences (SMD) to estimate treatment
      effects for continuous variables, and risk ratios (RR) for dichotomous effects,
      with their 95% confidence intervals (CIs). MAIN RESULTS: We identified 56
      completed trials of SSRI versus control, of which 52 trials (4059 participants)
      provided data for meta-analysis. There were statistically significant benefits of
      SSRI on both of the primary outcomes: RR for reducing dependency at the end of
      treatment was 0.81 (95% CI 0.68 to 0.97) based on one trial, and for disability
      score, the SMD was 0.91 (95% CI 0.60 to 1.22) (22 trials involving 1343
      participants) with high heterogeneity between trials (I(2) = 87%; P < 0.0001).
      For neurological deficit, depression and anxiety, there were statistically
      significant benefits of SSRIs. For neurological deficit score, the SMD was -1.00
      (95% CI -1.26 to -0.75) (29 trials involving 2011 participants) with high
      heterogeneity between trials (I(2) = 86%; P < 0.00001). For dichotomous
      depression scores, the RR was 0.43 (95% CI 0.24 to 0.77) (eight trials involving
      771 participants) with high heterogeneity between trials (I(2) = 77%; P <
      0.0001). For continuous depression scores, the SMD was -1.91 (95% CI -2.34 to 
      1.48) (39 trials involving 2728 participants) with high heterogeneity between
      trials (I(2) = 95%; P < 0.00001). For anxiety, the SMD was -0.77 (95% CI -1.52 to
      -0.02) (eight trials involving 413 participants) with high heterogeneity between
      trials (I(2) = 92%; P < 0.00001). There was no statistically significant benefit
      of SSRI on cognition, death, motor deficits and leaving the trial early. For
      cognition, the SMD was 0.32 (95% CI -0.23 to 0.86), (seven trials involving 425
      participants) with high heterogeneity between trials (I(2) = 86%; P < 0.00001).
      The RR for death was 0.76 (95% CI 0.34 to 1.70) (46 trials involving 3344
      participants) with no heterogeneity between trials (I(2) = 0%; P = 0.85). For
      motor deficits, the SMD was -0.33 (95% CI -1.22 to 0.56) (two trials involving
      145 participants). The RR for leaving the trial early was 1.02 (95% CI 0.86 to
      1.21) in favour of control, with no heterogeneity between trials. There was a non
      significant excess of seizures (RR 2.67; 95% CI 0.61 to 11.63) (seven trials
      involving 444 participants), a non-significant excess of gastrointestinal side
      effects (RR 1.90; 95% CI 0.94 to 3.85) (14 trials involving 902 participants) and
      a non-significant excess of bleeding (RR 1.63; 95% CI 0.20 to 13.05) (two trials
      involving 249 participants) in those allocated SSRIs. Data were not available on
      quality of life, fatigue or healthcare costs.There was no clear evidence from
      subgroup analyses that one SSRI was consistently superior to another, or that
      time since stroke or depression at baseline had a major influence on effect
      sizes. Sensitivity analyses suggested that effect sizes were smaller when we
      excluded trials at high or unclear risk of bias.Only eight trials provided data
      on outcomes after treatment had been completed; the effect sizes were generally
      in favour of SSRIs but CIs were wide. AUTHORS' CONCLUSIONS: SSRIs appeared to
      improve dependence, disability, neurological impairment, anxiety and depression
      after stroke, but there was heterogeneity between trials and methodological
      limitations in a substantial proportion of the trials. Large, well-designed
      trials are now needed to determine whether SSRIs should be given routinely to
      patients with stroke.

PMID- 23152274
TI  - Role of chemotherapy additional to high-dose methotrexate for primary central
      nervous system lymphoma (PCNSL).
AB  - BACKGROUND: Primary central nervous system lymphoma (PCNSL) is a variant of
      extranodal non-Hodgkin lymphoma (NHL) that accounts for about 2% to 5% of all
      primary intracranial tumours with immunocompetent patients. It appears at a
      median age of 62 years. A standard of care for PCNSL patients has not been
      defined yet, but high-dose methotrexate (HD-MTX) is considered to be a beneficial
      chemotherapy in PCNSL treatment. Currently, HD-MTX is combined with numerous
      other chemotherapy drugs to improve outcomes of HD-MTX monotherapy. However, the
      impact of additional chemotherapy remains unclear, as there is evidence of a
      higher risk of adverse events (AEs) such as infective complications. OBJECTIVES:
      We performed a systematic review of randomised controlled trials (RCTs) to assess
      the efficacy and safety of additional chemotherapy to HD-MTX in the treatment of
      immunocompetent PCNSL patients. SEARCH METHODS: We searched the Cochrane Central
      Register of Controlled Trials (CENTRAL) (The Cochrane Library 2012, Issue 5) and
      MEDLINE (from 1950 to May 2012) as well as conference proceedings for RCTs. Two
      review authors (NB, NS) independently screened search results. SELECTION
      CRITERIA: We included RCTs comparing HD-MTX in combination with additional
      chemotherapy to mono-chemotherapy with HD-MTX in immunocompetent patients off all
      ages in first-line treatment of PCNSL. DATA COLLECTION AND ANALYSIS: As an effect
      measure we used hazard ratios (HR) and 95% confidence intervals (CI) for overall
      survivals (OS) and progression-free survival (PFS). For effect measure of
      complete remission rate (CRR), partial response rate (PRR), treatment-related
      mortality (TRM) and AEs we used risk ratios (RR). Two review authors (NB, NS)
      independently extracted data and assessed the quality of trials. MAIN RESULTS:
      Our search strategies led to 699 potentially relevant references. Of these, one
      RCT involving 79 patients was included. We judged the quality of the trial as
      moderate. The study was reported as a randomised open-label study and published
      as a full-text article.Even though PFS was statistically significantly improved
      for patients treated with HD-MTX plus cytarabine (HR 0.54; 95% CI 0.31 to 0.92; P
      = 0.01), this did not translate to a statistical significant OS benefit (HR 0.65;
      95% CI 0.38 to 1.13; P = 0.07). AEs, especially infective complications,
      hepatotoxicity and haematological toxicities, were assessed more often in
      patients undergoing HD-MTX therapy combined with cytarabine. However, there were
      no statistically significant differences in terms of TRM (RR 3.08; 95% CI 0.33 to
      28.32; P = 0.35). AUTHORS' CONCLUSIONS: Owing to the small number of included
      trials and patients, the findings in this review remain uncertain. In summary,
      the presently available evidence (one small trial) showed a benefit in terms of
      PFS, ORR and CRR but no statistically significant difference regarding OS for
      patients with PCNSL treated with HD-MTX plus cytarabine compared to HD-MTX alone.
      However, the risk of severe infections and toxicity was significantly higher in
      patients treated with combined chemotherapy. More RCTs with additional
      chemotherapy to HD-MTX therapy with higher numbers of patients and longer follow
      up periods are needed to confirm the results of this review and determine whether
      the PFS benefit will translate into an OS advantage. At least the one included
      study shows that RCTs of moderate quality and with valuable outcomes for this
      malignant disease are feasible.

PMID- 23152275
TI  - Hypnosis for pain management during labour and childbirth.
AB  - BACKGROUND: This review is one in a series of Cochrane Reviews investigating pain
      management for childbirth. These reviews all contribute to an overview of
      systematic reviews of pain management for women in labour, and share a generic
      protocol. We examined the current evidence regarding the use of hypnosis for pain
      management during labour and childbirth. This review updates the findings
      regarding hypnosis from an earlier review of complementary and alternative
      therapies for pain management in labour into a stand-alone review. OBJECTIVES: To
      examine the effectiveness and safety of hypnosis for pain management during
      labour and childbirth. SEARCH METHODS: We searched the Cochrane Pregnancy and
      Childbirth Group's Trials Register (11 January 2012) and the reference lists of
      primary studies and review articles. SELECTION CRITERIA: Randomised controlled
      trials and quasi-randomised controlled trials comparing preparation for labour
      using hypnosis and/or use of hypnosis during labour, with or without concurrent
      use of pharmacological or non-pharmacological pain relief methods versus placebo,
      no treatment or any analgesic drug or technique. DATA COLLECTION AND ANALYSIS:
      Two assessors independently extracted data and assessed trial quality. Where
      possible we contacted study authors seeking additional information about data and
      methodology. MAIN RESULTS: We included seven trials randomising a total of 1213
      women. All but one of the trials were at moderate to high risk of bias. Although
      six of the seven trials assessed antenatal hypnotherapy, there were considerable
      differences between these trials in timing and technique. One trial provided
      hypnotherapy during labour. No significant differences between women in the
      hypnosis group and those in the control group were found for the primary
      outcomes: use of pharmacological pain relief (average risk ratio (RR) 0.63, 95%
      confidence interval (CI) 0.39 to 1.01, six studies, 1032 women), spontaneous
      vaginal birth (average RR 1.35, 95% CI 0.93 to 1.96, four studies, 472 women) or
      satisfaction with pain relief (RR 1.06, 95% CI 0.94 to 1.20, one study, 264
      women). There was significant statistical heterogeneity in the data for use of
      pharmacological pain relief and spontaneous vaginal birth. The primary outcome of
      sense of coping with labour was reported in two studies as showing no beneficial
      effect (no usable data available for this review).  For secondary outcomes, no
      significant differences were identified between women in the hypnosis group and
      women in the control group for most outcomes where data were available. For
      example, there was no significant difference for satisfaction with the childbirth
      experience (average RR 1.36, 95% CI 0.52 to 3.59, two studies, 370 women),
      admissions to the neonatal intensive care unit (average RR 0.58, 95% CI 0.12 to
      2.89, two studies, 347 women) or breastfeeding at discharge from hospital (RR
      1.00, 95% CI 0.97 to 1.03, one study, 304 women). There was some evidence of
      benefits for women in the hypnosis group compared with the control group for pain
      intensity, length of labour and maternal hospital stay, although these findings
      were based on single studies with small numbers of women. Pain intensity was
      found to be lower for women in the hypnosis group than those in the control group
      in one trial of 60 women (mean difference (MD) -0.70, 95% CI -1.03 to -0.37). The
      same study found that the average length of labour from 5 cm dilation to birth
      (minutes) was significantly shorter for women in the hypnosis group (mean
      difference -165.20, 95% CI -223.53 to -106.87, one study, 60 women). Another
      study found that a smaller proportion of women in the hypnosis group stayed in
      hospital for more than two days after the birth compared with women in the
      control group (RR 0.11, 95% CI 0.02 to 0.83, one study, 42 women). AUTHORS'
      CONCLUSIONS: There are still only a small number of studies assessing the use of
      hypnosis for labour and childbirth. Although the intervention shows some promise,
      further research is needed before recommendations can be made regarding its
      clinical usefulness for pain management in maternity care.

PMID- 23152277
TI  - Standard versus biofilm antimicrobial susceptibility testing to guide antibiotic
      therapy in cystic fibrosis.
AB  - BACKGROUND: The antibiotics used to treat pulmonary infections in people with
      cystic fibrosis are typically chosen based on the results of antimicrobial
      susceptibility testing performed on bacteria traditionally grown in a planktonic
      mode (grown in a liquid). However, there is considerable evidence to suggest that
      Pseudomonas aeruginosa actually grows in a biofilm (or slime layer) in the
      airways of cystic fibrosis patients with chronic pulmonary infections. Therefore,
      choosing antibiotics based on biofilm rather than conventional antimicrobial
      susceptibility testing could potentially improve response to treatment of
      Pseudomonas aeruginosa in people with cystic fibrosis. OBJECTIVES: To compare
      biofilm antimicrobial susceptibility testing-driven therapy to conventional
      antimicrobial susceptibility testing-driven therapy in the treatment of
      Pseudomonas aeruginosa infection in people with cystic fibrosis. SEARCH METHODS:
      We searched the Cochrane Cystic Fibrosis Trials Register, compiled from
      electronic database searches and handsearching of journals and conference
      abstract books. We also searched a registry of ongoing trials and the reference
      lists of relevant articles and reviews.Most recent search: 02 August 2012.
      SELECTION CRITERIA: Randomized controlled trials of antibiotic therapy based on
      biofilm antimicrobial susceptibility testing compared to antibiotic therapy based
      on conventional antimicrobial susceptibility testing in the treatment of
      Pseudomonas aeruginosa pulmonary infection in individuals with cystic fibrosis.
      DATA COLLECTION AND ANALYSIS: Both authors independently selected trials,
      assessed their risk of bias and extracted data from eligible trials.
      Additionally, the authors contacted the trial investigators to obtain further
      information. MAIN RESULTS: The search identified one multicentre, randomized,
      double-blind controlled clinical trial eligible for inclusion in the review (39
      participants). This trial prospectively assessed whether the use of biofilm
      antimicrobial susceptibility testing improved microbiological and clinical
      outcomes in participants with cystic fibrosis who were infected with Pseudomonas
      aeruginosa. The primary outcome was the change in sputum Pseudomonas aeruginosa
      density from the beginning to the end of antibiotic therapy. The mean (standard
      deviation) change in density in log(10) colony forming units per gram was -2.94
      (2.83) in the biofilm group and -3.27 (3.09) in the control group, for a mean
      difference of 0.28 (95% confidence interval -1.98 to 2.54) (P = 0.8). The data
      did not provide evidence that biofilm susceptibility testing was superior to
      conventional susceptibility testing. AUTHORS' CONCLUSIONS: The current evidence
      is insufficient to recommend choosing antibiotics based on biofilm antimicrobial
      susceptibility testing rather than conventional antimicrobial susceptibility
      testing in the treatment of Pseudomonas aeruginosa pulmonary infections in people
      with cystic fibrosis. Future randomized clinical trials on this topic may shed
      further light on this question.

PMID- 23152276
TI  - Haloperidol for psychosis-induced aggression or agitation (rapid
      tranquillisation).
AB  - BACKGROUND: Haloperidol, used alone is recommended to help calm situations of
      aggression with people with psychosis. This drug is widely accessible and may be
      the only antipsychotic medication available in areas where resources are limited.
      OBJECTIVES: To investigate whether haloperidol alone, administered orally,
      intramuscularly or intravenously, is effective treatment for psychosis-induced
      agitation or aggression. SEARCH METHODS: We searched the Cochrane Schizophrenia
      Group Trials Register (1st June 2011). SELECTION CRITERIA: Randomised controlled 
      trials (RCTs) involving people exhibiting agitation or aggression (or both)
      thought to be due to psychosis, allocated rapid use of haloperidol alone (by any
      route), compared with any other treatment. Outcomes included tranquillisation or
      asleep by 30 minutes, repeated need for rapid tranquillisation within 24 hours,
      specific behaviours (threat or injury to others/self), adverse effects. DATA
      COLLECTION AND ANALYSIS: We independently selected and assessed studies for
      methodological quality and extracted data. 'Summary of findings' tables were
      produced for each comparison grading the evidence and calculating, where possible
      and appropriate, a range of absolute effects. MAIN RESULTS: We included 32
      studies comparing haloperidol with 18 other treatments. Few studies were
      undertaken in circumstances that reflect real world practice, and, with notable
      exceptions, most were small and carried considerable risk of bias.Compared with
      placebo, more people in the haloperidol group were asleep at two hours (2 RCTs, n
      = 220, risk ratio (RR) 0.88, 95% confidence interval (CI) 0.82 to 0.95). Dystonia
      was common (2 RCTs, n = 207, RR 7.49, CI 0.93 to 60.21). Compared with
      aripiprazole, people in the haloperidol group required fewer injections than
      those in the aripiprazole group (2 RCTs, n = 473, RR 0.78, CI 0.62 to 0.99). More
      people in the haloperidol group experienced dystonia (2 RCTs, n = 477, RR 6.63,
      CI 1.52 to 28.86).Despite three larger trials with ziprasidone (total n = 739),
      data remain patchy, largely because of poor design and reporting. Compared with
      zuclopenthixol acetate, more people who received haloperidol required more than
      three injections (1 RCT, n = 70, RR 2.54, CI 1.19 to 5.46).Three trials (n = 205)
      compared haloperidol with lorazepam. There were no significant differences
      between the groups with regard to the number of participants asleep at one hour
      (1 RCT, n = 60, RR 1.05, CI 0.76 to 1.44). However, by three hours, significantly
      more people were asleep in the lorazepam group compared with the haloperidol
      group (1 RCT, n = 66, RR 1.93, CI 1.14 to 3.27). There were no differences in
      numbers requiring more than one injection (1 RCT, n = 66, RR 1.14, CI 0.91 to
      1.43).Haloperidol's adverse effects were not offset by addition of lorazepam
      (e.g. dystonia 1 RCT, n = 67, RR 8.25, CI 0.46 to 147.45; required antiparkinson
      medication RR 2.74, CI 0.81 to 9.25). Addition of promethazine was investigated
      in one larger and better graded trial (n = 316). More people in the haloperidol
      group were not tranquil or asleep by 20 minutes (RR 1.60, CI 1.18 to 2.16).
      Significantly more people in the haloperidol alone group experienced one or more
      adverse effects (RR 11.28, CI 1.47 to 86.35). Acute dystonia for those allocated
      haloperidol alone was too common for the trial to continue beyond the interim
      analysis (RR 19.48, CI 1.14 to 331.92). AUTHORS' CONCLUSIONS: If no other
      alternative exists, sole use of intramuscular haloperidol could be life-saving.
      Where additional drugs to offset the adverse effects are available, sole use of
      haloperidol for the extreme emergency, in situations of coercion, could be
      considered unethical. Addition of the sedating promethazine has support from
      better-grade evidence from within randomised trials. Use of an alternative
      antipsychotic drug is only partially supported by fragmented and poor-grade
      evidence. Evidence for use of newer generation antipsychotic alternatives is no
      stronger than that for older drugs. Adding a benzodiazepine to haloperidol does
      not have strong evidence of benefit and carries a risk of additional harm.After
      six decades of use for emergency rapid tranquillisation, this is still an area in
      need of good independent trials relevant to real world practice.

PMID- 23152278
TI  - Oral immunotherapy for milk allergy.
AB  - BACKGROUND: The mainstay of treatment of IgE-mediated cow milk allergy (IMCMA) is
      an avoidance diet, which is especially difficult with a ubiquitous food like
      milk. Milk oral immunotherapy (MOIT) may be an alternative treatment, through
      desensitization or induction of tolerance. OBJECTIVES: We aim to assess the
      clinical efficacy and safety of MOIT in children and adults with IMCMA as
      compared to a placebo treatment or avoidance strategy. SEARCH METHODS: We
      searched 13 databases for journal articles, conference proceedings, theses and
      unpublished trials, without language or date restrictions, using a combination of
      subject headings and text words. The search is up-to-date as of October 1, 2012.
      SELECTION CRITERIA: Only randomised controlled trials (RCT) were considered for
      inclusion. Blinded and open trial designs were included. Children and adults with
      IMCMA were included. MOIT administered by any protocol were included. DATA
      COLLECTION AND ANALYSIS: A total of 2111 unique records were identified and
      screened for potential inclusion. Studies were selected, data extracted and
      methodological quality assessed independently by two reviewers. We attempted to
      contact the study investigators to inquire about data not published that was
      required for the analysis. Statistical heterogeneity was assessed using the I2
      test. We estimated a pooled risk ratio (RR) for each outcome using a Mantel
      Haenzel fixed-effect model if statistical heterogeneity was low as evaluated by
      an I2 value less than 50%. MAIN RESULTS: Of 157 records reviewed, 16 were
      included, representing five trials. In general, the studies were small and had
      inconsistent methodological rigor. Overall, the quality of evidence was rated as
      low. Each study used a different MOIT protocol. A total of 196 patients were
      studied (106 MOIT, 90 control) and all were children. Three studies were blinded
      and two used an avoidance diet control.  Sixty-six patients (62%) in the MOIT
      group were able to tolerate a full serving of milk (about 200 mL) compared to
      seven (8%) of the control group (RR 6.61, 95% CI 3.51 to 12.44). In addition, 27
      (25%) in the MOIT group could ingest a partial serving of milk (10 to 184 mL)
      while none could in the control group (RR 9.34, 95% CI 2.72 to 32.09). None of
      the studies assessed the patients following a period off immunotherapy. Adverse
      reactions were common (97 of 106 MOIT patients had at least one symptom),
      although most were local and mild. Because of variability in reporting methods,
      adverse effects could not be combined quantitatively. For every 11 patients
      receiving MOIT, one required intramuscular epinephrine. One patient required it
      on two occasions. AUTHORS' CONCLUSIONS: Studies to date have involved small
      numbers of patients and the quality of evidence is generally low. The current
      evidence shows that MOIT can lead to desensitization in the majority of
      individuals with IMCMA although the development of long-term tolerance has not
      been established. A major drawback of MOIT is the frequency of adverse effects,
      although most are mild and self-limited. The use of parenteral epinephrine is not
      infrequent. Because there are no standardized protocols, guidelines would be
      required prior to incorporating desensitization into clinical practice.

PMID- 23152279
TI  - Different types of intermittent pneumatic compression devices for preventing
      venous thromboembolism in patients after total hip replacement.
AB  - BACKGROUND: Total hip replacement (THR) is an effective treatment for reducing
      pain and improving function and quality of life in patients with hip disorders.
      While this operation is very successful, deep vein thrombosis (DVT) and pulmonary
      embolism (PE) are significant complications after THR. Different types of
      intermittent pneumatic compression (IPC) devices have been used for thrombosis
      prophylaxis in patients following THR. Available devices differ in compression
      garments, location of air bladders, patterns of pump pressure cycles, compression
      profiles, cycle length, duration of inflation time and deflation time, or cycling
      mode such as automatic or constant cycling devices. Despite the widely accepted
      use of IPC for the treatment of arterial and venous diseases, the relative
      effectiveness of different types of IPC systems as prophylaxis against thrombosis
      after THR is still unclear. OBJECTIVES: To assess the comparative effectiveness
      and safety of different IPC devices with respect to the prevention of venous
      thromboembolism in patients after THR. SEARCH METHODS: The Cochrane Peripheral
      Vascular Diseases Group Trials Search Coordinator searched the Specialised
      Register (May 2012), CENTRAL (2012, Issue 4), MEDLINE (April Week 3 2012) and
      EMBASE (Week 17 2012). Clinical trial databases were searched for details of
      ongoing and unpublished studies. Reference lists of obtained articles were also
      screened. There were no limits imposed on language or publication status.
      SELECTION CRITERIA: Randomized and quasi-randomized controlled studies were
      eligible for inclusion. DATA COLLECTION AND ANALYSIS: Two review authors
      independently selected trials, assessed trials for eligibility and methodological
      quality, and extracted data. Disagreement was resolved by discussion or, if
      necessary, referred to a third review author. MAIN RESULTS: Only one quasi
      randomized controlled study with 121 study participants comparing two types of
      IPC devices met the inclusion criteria. The authors found no cases of symptomatic
      DVT or PE in either the calf-thigh compression group or the plantar compression
      group during the first three weeks after the THR. The calf-thigh pneumatic
      compression was more effective than plantar compression for reducing thigh
      swelling during the early postoperative stage. The strength of the evidence in
      this review is weak as only one trial was included and it was classified as
      having a high risk of bias. AUTHORS' CONCLUSIONS: There is a lack of evidence
      from randomized controlled trials to make an informed choice of IPC device for
      preventing venous thromboembolism (VTE) following total hip replacement. More
      research is urgently required, ideally a multicenter, properly designed RCT
      including a sufficient number of participants. Clinically relevant outcomes such
      as mortality, imaging-diagnosed asymptomatic VTE and major complications must be
      considered.

PMID- 23152280
TI  - Flupenthixol versus placebo for schizophrenia.
AB  - BACKGROUND: Flupenthixol, first made available in the UK in 1965, has been used
      as a treatment for schizophrenia for decades. OBJECTIVES: To evaluate the
      absolute clinical effects of flupenthixol for schizophrenia in comparison with
      placebo. SEARCH METHODS: We searched the Cochrane Schizophrenia Group Trials
      Register (August 2011), inspected references of all included or excluded studies
      for further trials, and contacted authors of trials for additional information.
      SELECTION CRITERIA: All randomised controlled trials (RCTs) that compared
      flupenthixol with placebo for adults with schizophrenia or related disorders by
      any means of diagnosis. Primary outcomes of interest were clinically important
      change in global state, mental state and behaviour, and adverse effects. DATA
      COLLECTION AND ANALYSIS: We extracted data from the one included study, discussed
      any disagreement, documented decisions and contacted the authors of the included
      study for further information. We analysed binary outcomes using a standard
      estimation of the risk ratio (RR) and its 95% confidence intervals (CI). For
      homogenous data we used a fixed-effect model. For rare events we analysed
      dichotomous data using Peto Odds ratio (OR), again with 95% CIs. MAIN RESULTS: We
      could include only one small (n = 45) study of moderate quality. When the active
      alpha-flupenthixol was compared with the inactive placebo or beta-flupenthixol
      groups combined, fewer people in the active treatment group needed additional
      antipsychotic medication by around four weeks for deterioration in their general
      state (n = 45, OR 0.19 CI 0.05 to 0.71). There was no clear difference in social
      functioning at one year (n = 45, RR 1.33 CI 0.91 to 1.96). We found no clear data
      on mental state and behaviour, adverse effects, service use, satisfaction with
      treatment or costs. AUTHORS' CONCLUSIONS: We were surprised that this well
      established drug had so few data from trials investigating its absolute effects.
      We think this is unlikely to be rectified some 50 years after its launch and know
      that this would not happen today. However, even though data are very limited,
      flupenthixol may well be worthy of careful investigation - partly to ensure that
      this inexpensive active drug is not forgotten.

PMID- 23152281
TI  - Hormonal and intrauterine methods for contraception for women aged 25 years and
      younger.
AB  - BACKGROUND: Women between the ages of 15 and 24 years have high rates of
      unintended pregnancy; over half of women in this age group want to avoid
      pregnancy. However, women under age 25 years have been found to have higher
      typical contraceptive failure rates within the first 12 months of use than older
      women. High discontinuation rates may also be a problem in this population.
      Concern that adolescents and young women will not find hormonal or intrauterine
      contraceptives acceptable or effective might deter healthcare providers from
      recommending these contraceptive methods.  OBJECTIVES: This review examined
      randomized controlled trials of hormonal or intrauterine methods used for
      contraception in women aged 25 years and younger. SEARCH METHODS: In February
      2012, we searched the computerized databases Cochrane Register of Controlled
      Trials (CENTRAL), MEDLINE, EMBASE, POPLINE, CINAHL, and LILACS for randomized
      controlled trials that compared hormonal or intrauterine methods used for
      contraception in women aged 25 years and younger. We also searched for current
      trials via ClinicalTrials.gov and the World Health Organization International
      Clinical Trials Registry Platform (ICTRP). SELECTION CRITERIA: We considered all
      randomized controlled trials in any language that reported the contraceptive
      failure rates for hormonal or intrauterine contraceptive methods, when compared
      to another contraceptive method, for women aged 25 years and younger. The other
      contraceptive method could be another intrauterine method, another hormonal
      method, or a non-hormonal method. Treatment duration must have been at least
      three months. DATA COLLECTION AND ANALYSIS: The first author extracted the data
      and entered the information into RevMan. Another author performed an independent
      data extraction and verified the initial entry. Because of disparate
      contraceptive exposures, we were not able to combine the studies in meta
      analysis. MAIN RESULTS: Four trials met the inclusion criteria. The trials
      compared the combined oral contraceptive versus the transdermal contraceptive
      patch, the combined oral contraceptive versus the vaginal contraceptive ring, the
      combined oral contraceptive versus the levonorgestrel intrauterine system, and
      the levonorgestrel intrauterine system versus the copper T380A intrauterine
      device. Because of small numbers of participants, the trials were not informative
      regarding contraceptive efficacy. Data on continuation rates were also limited.
      In one of these trials, the levonorgestrel intrauterine system was found to have
      a similar 12-month continuation rate as the combined oral contraceptive (odds
      ratio (OR) 1.48; 95% CI 0.76 to 2.89). In that trial, a higher proportion of
      women discontinued the levonorgestrel intrauterine system because of pain (OR
      14.62; 95% CI 0.81 to 263.16), whereas a higher proportion of women discontinued
      the combined oral contraceptive for personal reasons (OR 0.27; 95% CI 0.09 to
      0.85). AUTHORS' CONCLUSIONS: Current evidence is insufficient to compare
      contraceptive efficacy and continuation rates for hormonal and intrauterine
      methods in women aged 25 years and younger. Limited data suggests that the
      levonorgestrel intrauterine system may be an acceptable alternative to the
      combined oral contraceptive in this population.

PMID- 23152282
TI  - Omega 3 fatty acids for preventing or slowing the progression of age-related
      macular degeneration.
AB  - BACKGROUND: Evidence from animal models and observational studies in humans has
      suggested that there is an inverse relationship between dietary intake of omega 3
      long-chain polyunsaturated fatty acids (LCPUFA) and risk of developing age
      related macular degeneration (AMD) or progressing to advanced AMD. OBJECTIVES: To
      review the evidence that increasing the levels of omega 3 LCPUFA in the diet
      (either by eating more foods rich in omega 3 or by taking nutritional
      supplements) prevents AMD or slows the progression of AMD. SEARCH METHODS: We
      searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials
      Register) (The Cochrane Library 2012, Issue 4), MEDLINE (January 1950 to April
      2012), EMBASE (January 1980 to April 2012), Latin American and Caribbean
      Literature on Health Sciences (LILACS) (January 1982 to April 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. The
      electronic databases were last searched on 26 April 2012. SELECTION CRITERIA: We
      planned to include randomised controlled trials (RCTs) where increased dietary
      intake of omega 3 fatty acids was compared to placebo or no intervention with the
      aim of preventing the development of AMD, or slowing its progression. DATA
      COLLECTION AND ANALYSIS: Both authors independently screened titles, abstracts
      and full-texts of articles to identify studies for inclusion and analysis. MAIN
      RESULTS: No trials met the selection criteria. The results of a large, multi
      centre, randomised trial (AREDS2) that will assess the effects of oral
      supplementation with omega 3 LCPUFA on progression to advanced AMD are expected
      in 2013. Two further trials are also ongoing.  AUTHORS' CONCLUSIONS: Until data
      from RCTs become available for analysis, there is currently no evidence to
      support increasing levels of omega 3 LCPUFA in the diet for the explicit purpose
      of preventing or slowing the progression of AMD.

PMID- 23152283
TI  - Preoperative physical therapy for elective cardiac surgery patients.
AB  - BACKGROUND: After cardiac surgery, physical therapy is a routine procedure
      delivered with the aim of preventing postoperative pulmonary complications.
      OBJECTIVES: To determine if preoperative physical therapy with an exercise
      component can prevent postoperative pulmonary complications in cardiac surgery
      patients, and to evaluate which type of patient benefits and which type of
      physical therapy is most effective. SEARCH METHODS: Searches were run on the
      Cochrane Central Register of Controlled Trials (CENTRAL) on the Cochrane Library
      (2011, Issue 12 ); MEDLINE (1966 to 12 December 2011); EMBASE (1980 to week 49,
      2011); the Physical Therapy Evidence Database (PEDro) (to 12 December 2011) and
      CINAHL (1982 to 12 December 2011). SELECTION CRITERIA: Randomised controlled
      trials or quasi-randomised trials comparing preoperative physical therapy with no
      preoperative physical therapy or sham therapy in adult patients undergoing
      elective cardiac surgery. DATA COLLECTION AND ANALYSIS: Data were collected on
      the type of study, participants, treatments used, primary outcomes (postoperative
      pulmonary complications grade 2 to 4: atelectasis, pneumonia, pneumothorax,
      mechanical ventilation > 48 hours, all-cause death, adverse events) and secondary
      outcomes (length of hospital stay, physical function measures, health-related
      quality of life, respiratory death, costs). Data were extracted by one review
      author and checked by a second review author. Review Manager 5.1 software was
      used for the analysis. MAIN RESULTS: Eight randomised controlled trials with 856
      patients were included. Three studies used a mixed intervention (including either
      aerobic exercises or breathing exercises); five studies used inspiratory muscle
      training. Only one study used sham training in the controls. Patients that
      received preoperative physical therapy had a reduced risk of postoperative
      atelectasis (four studies including 379 participants, relative risk (RR) 0.52;
      95% CI 0.32 to 0.87; P = 0.01) and pneumonia (five studies including 448
      participants, RR 0.45; 95% CI 0.24 to 0.83; P = 0.01) but not of pneumothorax
      (one study with 45 participants, RR 0.12; 95% CI 0.01 to 2.11; P = 0.15) or
      mechanical ventilation for > 48 hours after surgery (two studies with 306
      participants, RR 0.55; 95% CI 0.03 to 9.20; P = 0.68). Postoperative death from
      all causes did not differ between groups (three studies with 552 participants, RR
      0.66; 95% CI 0.02 to 18.48; P = 0.81). Adverse events were not detected in the
      three studies that reported on them. The length of postoperative hospital stay
      was significantly shorter in experimental patients versus controls (three studies
      with 347 participants, mean difference -3.21 days; 95% CI -5.73 to -0.69; P =
      0.01). One study reported a reduced physical function measure on the six-minute
      walking test in experimental patients compared to controls. One other study
      reported a better health-related quality of life in experimental patients
      compared to controls. Postoperative death from respiratory causes did not differ
      between groups (one study with 276 participants, RR 0.14; 95% CI 0.01 to 2.70; P
      = 0.19). Cost data were not reported on. AUTHORS' CONCLUSIONS: Evidence derived
      from small trials suggests that preoperative physical therapy reduces
      postoperative pulmonary complications (atelectasis and pneumonia) and length of
      hospital stay in patients undergoing elective cardiac surgery. There is a lack of
      evidence that preoperative physical therapy reduces postoperative pneumothorax,
      prolonged mechanical ventilation or all-cause deaths.

PMID- 23152284
TI  - General health checks in adults for reducing morbidity and mortality from
      disease.

PMID- 23152285
TI  - Consolidated standards of reporting trials (CONSORT) and the completeness of
      reporting of randomised controlled trials (RCTs) published in medical journals.
AB  - BACKGROUND: An overwhelming body of evidence stating that the completeness of
      reporting of randomised controlled trials (RCTs) is not optimal has accrued over
      time. In the mid-1990s, in response to these concerns, an international group of
      clinical trialists, statisticians, epidemiologists, and biomedical journal
      editors developed the CONsolidated Standards Of Reporting Trials (CONSORT)
      Statement. The CONSORT Statement, most recently updated in March 2010, is an
      evidence-based minimum set of recommendations including a checklist and flow
      diagram for reporting RCTs and is intended to facilitate the complete and
      transparent reporting of trials and aid their critical appraisal and
      interpretation. In 2006, a systematic review of eight studies evaluating the
      "effectiveness of CONSORT in improving reporting quality in journals" was
      published. OBJECTIVES: To update the earlier systematic review assessing whether
      journal endorsement of the 1996 and 2001 CONSORT checklists influences the
      completeness of reporting of RCTs published in medical journals. SEARCH METHODS:
      We conducted electronic searches, known item searching, and reference list scans
      to identify reports of evaluations assessing the completeness of reporting of
      RCTs. The electronic search strategy was developed in MEDLINE and tailored to
      EMBASE. We searched the Cochrane Methodology Register and the Cochrane Database
      of Systematic Reviews using the Wiley interface. We searched the Science Citation
      Index, Social Science Citation Index, and Arts and Humanities Citation Index
      through the ISI Web of Knowledge interface. We conducted all searches to identify
      reports published between January 2005 and March 2010, inclusive. SELECTION
      CRITERIA: In addition to studies identified in the original systematic review on
      this topic, comparative studies evaluating the completeness of reporting of RCTs
      in any of the following comparison groups were eligible for inclusion in this
      review: 1) Completeness of reporting of RCTs published in journals that have and
      have not endorsed the CONSORT Statement; 2) Completeness of reporting of RCTs
      published in CONSORT-endorsing journals before and after endorsement; or 3)
      Completeness of reporting of RCTs before and after the publication of the CONSORT
      Statement (1996 or 2001). We used a broad definition of CONSORT endorsement that
      includes any of the following: (a) requirement or recommendation in journal's
      'Instructions to Authors' to follow CONSORT guidelines; (b) journal editorial
      statement endorsing the CONSORT Statement; or (c) editorial requirement for
      authors to submit a CONSORT checklist and/or flow diagram with their manuscript.
      We contacted authors of evaluations reporting data that could be included in any
      comparison group(s), but not presented as such in the published report and asked
      them to provide additional data in order to determine eligibility of their
      evaluation. Evaluations were not excluded due to language of publication or
      validity assessment. DATA COLLECTION AND ANALYSIS: We completed screening and
      data extraction using standardised electronic forms, where conflicts, reasons for
      exclusion, and level of agreement were all automatically and centrally managed in
      web-based management software, DistillerSR((r)). One of two authors extracted
      general characteristics of included evaluations and all data were verified by a
      second author. Data describing completeness of reporting were extracted by one
      author using a pre-specified form; a 10% random sample of evaluations was
      verified by a second author. Any discrepancies were discussed by both authors; we
      made no modifications to the extracted data. Validity assessments of included
      evaluations were conducted by one author and independently verified by one of
      three authors. We resolved all conflicts by consensus.For each comparison we
      collected data on 27 outcomes: 22 items of the CONSORT 2001 checklist, plus four
      items relating to the reporting of blinding, and one item of aggregate CONSORT
      scores. Where reported, we extracted and qualitatively synthesised data on the
      methodological quality of RCTs, by scale or score. MAIN RESULTS: Fifty-three
      publications reporting 50 evaluations were included. The total number of RCTs
      assessed within evaluations was 16,604 (median per evaluation 123 (interquartile
      range (IQR) 77 to 226) published in a median of six (IQR 3 to 26) journals.
      Characteristics of the included RCT populations were variable, resulting in
      heterogeneity between included evaluations. Validity assessments of included
      studies resulted in largely unclear judgements. The included evaluations are not
      RCTs and less than 8% (4/53) of the evaluations reported adjusting for potential
      confounding factors.   Twenty-five of 27 outcomes assessing completeness of
      reporting in RCTs appeared to favour CONSORT-endorsing journals over non
      endorsers, of which five were statistically significant. 'Allocation concealment'
      resulted in the largest effect, with risk ratio (RR) 1.81 (99% confidence
      interval (CI) 1.25 to 2.61), suggesting that 81% more RCTs published in CONSORT
      endorsing journals adequately describe allocation concealment compared to those
      published in non-endorsing journals. Allocation concealment was reported
      adequately in 45% (393/876) of RCTs in CONSORT-endorsing journals and in 22%
      (329/1520) of RCTs in non-endorsing journals. Other outcomes with results that
      were significant include: scientific rationale and background in the
      'Introduction' (RR 1.07, 99% CI 1.01 to 1.14); 'sample size' (RR 1.61, 99% CI
      1.13 to 2.29); method used for 'sequence generation' (RR 1.59, 99% CI 1.38 to
      1.84); and an aggregate score over reported CONSORT items, 'total sum score'
      (standardised mean difference (SMD) 0.68 (99% CI 0.38 to 0.98)). AUTHORS'
      CONCLUSIONS: Evidence has accumulated to suggest that the reporting of RCTs
      remains sub-optimal. This review updates a previous systematic review of eight
      evaluations. The findings of this review are similar to those from the original
      review and demonstrate that, despite the general inadequacies of reporting of
      RCTs, journal endorsement of the CONSORT Statement may beneficially influence the
      completeness of reporting of trials published in medical journals. Future
      prospective studies are needed to explore the influence of the CONSORT Statement
      dependent on the extent of editorial policies to ensure adherence to CONSORT
      guidance.

PMID- 23152286
TI  - Determination of the domain structure of the 7S and 11S globulins from soy
      proteins by XRD and FTIR.
AB  - BACKGROUND: The 7S and 11S fractions from soybean proteins have interesting high
      nutritional and excellent functional properties. The aim of this research was to
      improve the functional properties of soy proteins by studying the effect of bis(2
      ethylhexyl) sodium sulfosuccinate (AOT) reverse micelles on the conformation of
      the 7S and 11S globulins using Fourier transform infrared and X-ray diffraction
      spectroscopy. RESULTS: Fourier transform infrared revealed that the intensity of
      the 7S and 11S globulin bands from AOT reverse micelle extraction at 1600-1700,
      1480-1575, 1220-1300, 3330, 1448 and 1395 cm(-1) was higher than from aqueous
      buffer. X-ray diffraction data showed that the intensities of 7S globulin using
      two extraction methods at 2theta about 10 degrees  were significantly different
      (P < 0.05), about 22 degrees  slightly increased. The intensities of 11S globulin
      at 2theta about 10 degrees  and 22 degrees  were similar. The average distance
      between particles (dhkl ) for 7S globulin with aqueous buffer extraction at
      2theta about 10 degrees  was greater than AOT reverse micelle extraction.
      CONCLUSION: This study showed the potential of reverse micelles as a protocol for
      extracting the 7S and 11S globulins for analytical purposes. The results
      represent a new avenue for determining the structures of the 7S and 11S
      globulins.

PMID- 23152287
TI  - The Contegra valved bovine conduit: a biomaterial for the surgical treatment of
      congenital heart defects.
AB  - Contegra, a bovine jugular vein graft, has been widely used as a preferable
      biomaterial in the surgical treatment of congenital heart defects, especially as
      a conduit for the right ventricular outflow tract reconstruction. This article
      aims to make a comprehensive review on the clinical outcomes of Contegra. Reports
      of Contegra published since 2002 were comprehensively retrieved, collected and
      analyzed. There were 1718 Contegra, applied in 1705 patients. The sizes of the
      conduits were 8-22 mm. The patients aged from newborn to 74.5 years, prevailed by
      pediatrics. The primary diagnosis was congenital heart defects in all cases, with
      Tetralogy of Fallot, truncus arteriosus and pulmonary atresia being the first
      three diagnoses, representing 25.6%, 16.7%, and 13.1%, respectively. Contegra was
      used as a tube graft in the pulmonary position in 1635 (95.9%) patients, as a
      monocuspid patch in 12 (0.7%), as a graft in the position of the pulmonary valve
      or a monocusps in 40 (2.3%), and as an inferior vena cava-pulmonary artery
      conduit in the Fontan procedure in 18 (1.1%) patients, respectively. Conduit
      reimplantation was performed in 141 (8.3%) patients 33.8 +/- 37 (8.6-106.8)
      months after the initial conduit insertion. Conduit plasty was necessary in 6
      (0.4%), and reintervention in 83 (4.9%) patients. Indications for conduit
      reimplantation included severe stenosis of the distal anastomosis, pseudoaneurysm
      of the proximal anastomosis and severe conduit regurgitation. As for the good
      performance, availability and longevity, Contegra is a biomaterial suitable for
      the right ventricular outflow tract reconstruction and for patch repair for
      ventricular septal defect, but not apt for Fontan procedure.

PMID- 23152288
TI  - Assessment of stent strut endothelialization in iliac arteries of rabbits.
AB  - BACKGROUND: Fast post-implantation stent endothelialization is desirable for
      theoretically reducing the possibility of stent thrombosis. OBJECTIVE: To
      evaluate the extent of sirolimus-eluting stent strut endothelialization
      (delivered from the luminal and abluminal aspects or abluminal aspect only) in
      the iliac arteries of rabbits. METHODS: The iliac arteries of 10 rabbits were
      implanted with four sirolimus-eluting stents in the luminal and abluminal
      aspects, three sirolimus-eluting stents in the abluminal aspect, six polymer
      coated stents, and four uncoated stents. After four weeks, the rabbits were
      euthanized and scanning electron microscopy was performed to quantify the area of
      exposed stent strut as well as the percentage of endothelialization. RESULTS: The
      area (mean +/- SD) (mm(2)) of exposed uncoated stent struts, polymer-coated
      stents, sirulimus-eluting stent in the abluminal and luminal aspects and
      sirolimus-eluting stent in the abluminal aspect was 0.12 +/- 0.08, 0.09 +/- 0.12,
      0.60 +/- 0.67 and 0.05 +/- 0.04, respectively (p = 0.120). The percentage of
      endothelialization (mean +/- SD) (%) of uncoated stents, polymer-coated stents,
      sirolimus-eluting stents in the luminal and abluminal aspects and sirolimus
      eluting stents in the abluminal aspect was 99 +/- 01, 99 +/- 0. 97 +/- 03 and 99
      +/- 0, respectively (p = 0.133). CONCLUSION: After four weeks of implantation in
      the iliac arteries of rabbits, both the sirolimus-eluting stents in the luminal
      plus abluminal aspects and those in the abluminal aspect only showed stent strut
      endothelialization rates similar to those of the other types of non-drug eluting
      stents.

PMID- 23152289
TI  - NT-Pro-BNP levels and their response to exercise in patients with slow coronary
      flow.
AB  - BACKGROUND: Natriuretic peptides are released by the heart in response to wall
      stress. OBJECTIVE: The NT-Pro-BNP concentrations in slow coronary flow (SCF)
      patients were assessed before and after the exercise test and compared with the
      values of healthy controls. METHODS: The study population was 34 patients with
      SCF [22 males (64.7%), aged 51.0 +/- 6.2 years], and 34 normal subjects with
      normal coronary arteries [21 males (61.8%), aged 53.2 +/- 6.6 years]. Coronary
      flow rates of all patients and control subjects were documented as Thrombolysis
      in Myocardial Infarction (TIMI) frame count. Blood samples were drawn at rest and
      after the exercise testing. RESULTS: The baseline NT-Pro-BNP concentrations of
      the SCF patients were higher than those of the control subjects (NT-Pro-BNP: 49.7
      +/- 14.2 pg/mL vs. 25.3 +/- 4.6 pg/mL p<0.0001, respectively), and this
      difference increased after exercise test between the groups (NT-Pro-BNP: 69.5 +/-
      18.6 pg/mL vs. 30.9 +/- 6.4 pg/mL p<0.0001). In SCF group after exercise, NT-Pro
      BNP concentration in 15 patients with angina was higher than those without angina
      (76.8 +/- 17.8 pg/mL vs. 63.8 +/- 17.5 pg/mL p=0.041). NT-Pro-BNP concentration
      in 11 patients with ST depression was also higher than those without ST
      depression (82.4 +/- 17.3 pg/mL vs. 63.3 +/- 16.1 pg/mL p=0.004). Median post
      exercise increases in NT-Pro-BNP (Delta NT-Pro-BNP) were higher in the SCF group
      than in the control group (Delta NT-Pro-BNP: 19.8 +/- 7.7 pg/mL vs. 5.7 +/- 4.5
      pg/mL p<0.0001). CONCLUSION: The results of this study suggest that there may be
      an important pathophysiologic link between the severity of SCF (microvascular or
      epicardial coronary artery dysfunction) and the level of circulating NT-Pro-BNP
      in SCF patients.

PMID- 23152290
TI  - Transthoracic impedance compared to magnetic resonance imaging in the assessment
      of cardiac output.
AB  - BACKGROUND: Cardiac magnetic resonance imaging is considered the gold-standard
      method for the calculation of cardiac volumes. Transthoracic impedance
      cardiography assesses the cardiac output. No studies validating this measurement,
      in comparison to that obtained by magnetic resonance imaging, are available.
      OBJECTIVE: To evaluate the performance of transthoracic impedance cardiography in
      the calculation of the cardiac output, cardiac index and stroke volume using
      magnetic resonance imaging as the gold-standard. METHODS: 31 patients with a mean
      age of 56.7 +/- 18 years were assessed; of these, 18 (58%) were males. Patients
      whose indication for magnetic resonance imaging required pharmacologic stress
      test were excluded. Correlation between methods was assessed using the Pearson's
      coefficient, and dispersion of absolute differences in relation to the mean was
      demonstrated using the Bland-Altman's method. Agreement between methods was
      analyzed using the intraclass correlation coefficient. RESULTS: The mean cardiac
      output by transthoracic impedance cardiography and by magnetic resonance imaging
      was 5.16 +/- 0.9 and 5.13 +/- 0.9 L/min, respectively. Good agreement between
      methods was observed for cardiac output (r = 0.79; p = 0.0001), cardiac index (r
      = 0.74; p = 0.0001) and stroke volume (r = 0.88; p = 0.0001). The analysis by the
      Bland-Altman plot showed low dispersion of differences in relation to the mean,
      with a low amplitude of agreement intervals. Good agreement between the two
      methods was observed when analyzed by the intraclass correlation coefficient,
      with coefficients for cardiac output, cardiac index and stroke volume of 0.78,
      0.73 and 0.88, respectively (p < 0.0001 for all comparisons). CONCLUSION:
      Transthoracic impedance cardiography proved accurate in the calculation of the
      cardiac output in comparison to cardiac magnetic resonance imaging.

PMID- 23152291
TI  - Atrial fibrillation and dementia: results from the Sao Paulo ageing & health
      study.
AB  - BACKGROUND: Atrial fibrillation (AF) is a controversial risk factor for dementia.
      OBJECTIVE: The objective of this study was to assess the association between AF
      and dementia in the "Sao Paulo Ageing & Health" (SPAH) study participants.
      METHODS: SPAH is a cross-sectional, population-based study of elderly people
      living in a deprived neighborhood in Sao Paulo, Brazil. Dementia diagnosis was
      performed according to the 10/66 study group protocol based on Diagnostic and
      Statistical Manual of Mental Disorders (DSM-IV) criteria. Diagnosis of AF was
      made using a 12-lead electrocardiogram (ECG) recording, which was assessed by two
      cardiologists. Data on demographics and cardiovascular risk factors were also
      obtained. RESULTS: Dementia was diagnosed in 66 (4.3%) and AF in 36 (2.4%) of
      1,524 participants with a valid ECG. The crude odds ratio (OR) for dementia in
      participants with AF was 2.8 (95% confidence interval [CI]: 1.0-8.1; p=0.06)
      compared with individuals without AF. When analyzing data according to sex, a
      positive relationship was found in women (OR 4.2; 95% CI: 1.24-15.1; p=0.03).
      After age-adjustment, however, this association was no longer significant (OR
      2.2; 95% CI: 0.6-8.9; p=0.26). CONCLUSION: There was no independent association
      between AF and dementia in this sample. The prevalence of AF may be low in this
      population owing to premature cardiovascular death.

PMID- 23152292
TI  - Knockout of Na-glucose transporter SGLT2 attenuates hyperglycemia and glomerular
      hyperfiltration but not kidney growth or injury in diabetes mellitus.
AB  - The Na-glucose cotransporter SGLT2 mediates high-capacity glucose uptake in the
      early proximal tubule and SGLT2 inhibitors are developed as new antidiabetic
      drugs. We used gene-targeted Sglt2 knockout (Sglt2(-/-)) mice to elucidate the
      contribution of SGLT2 to blood glucose control, glomerular hyperfiltration,
      kidney growth, and markers of renal growth and injury at 5 wk and 4.5 mo after
      induction of low-dose streptozotocin (STZ) diabetes. The absence of SGLT2 did not
      affect renal mRNA expression of glucose transporters SGLT1, NaGLT1, GLUT1, or
      GLUT2 in response to STZ. Application of STZ increased blood glucose levels to a
      lesser extent in Sglt2(-/-) vs. wild-type (WT) mice (~300 vs. 470 mg/dl) but
      increased glucosuria and food and fluid intake to similar levels in both
      genotypes. Lack of SGLT2 prevented STZ-induced glomerular hyperfiltration but not
      the increase in kidney weight. Knockout of SGLT2 attenuated the STZ-induced renal
      accumulation of p62/sequestosome, an indicator of impaired autophagy, but did not
      attenuate the rise in renal expression of markers of kidney growth (p27 and
      proliferating cell nuclear antigen), oxidative stress (NADPH oxidases 2 and 4 and
      heme oxygenase-1), inflammation (interleukin-6 and monocyte chemoattractant
      protein-1), fibrosis (fibronectin and Sirius red-sensitive tubulointerstitial
      collagen accumulation), or injury (renal/urinary neutrophil gelatinase-associated
      lipocalin). SGLT2 deficiency did not induce ascending urinary tract infection in
      nondiabetic or diabetic mice. The results indicate that SGLT2 is a determinant of
      hyperglycemia and glomerular hyperfiltration in STZ-induced diabetes mellitus but
      is not critical for the induction of renal growth and markers of renal injury,
      inflammation, and fibrosis.

PMID- 23152294
TI  - Isolation of interstitial fluid and demonstration of local proinflammatory
      cytokine production and increased absorptive gradient in chronic peritoneal
      dialysis.
AB  - In peritoneal dialysis (PD) patients, the frequent exposure to "unphysiological"
      dialysis fluids elicits a chronic state of a low-grade peritoneal inflammation
      leading to interstitial matrix remodeling and angiogenesis. Proinflammatory
      cytokines are important regulators involved in this inflammatory process that
      ultimately leads to dysfunction of the peritoneum as a dialysis membrane. We
      aimed to measure the local concentrations of proinflammatory cytokines in the
      peritoneal interstitial fluid (IF). Furthermore, we wanted to assess how the
      driving forces for fluid and solute exchanges are affected in a remodeled
      interstitial matrix and thus measured the colloid osmotic pressure (COP) gradient
      in rats that were exposed to chronic PD. After 8 wk of peritoneal dialysis, IF
      from peritoneum was isolated using a centrifugation method, and was analyzed for
      cytokine content and COP along with plasma. For several of the proinflammatory
      cytokines there were gradients from IF to plasma, showing local production. For
      some cytokines, the concentration in IF was increased severalfold, whereas IL-18
      was increased systemically due to PD. Furthermore, the presence of the catheter
      per se seemed to increase cytokine levels. COP in IF was significantly decreased
      in the PD group, while collagen and hyaluronan content was increased.
      Collectively, our data suggest that the increased levels of proinflammatory
      cytokines after PD may be an integral component of the development of fibrosis
      and angiogenesis commonly seen in PD patients, and the decreased COP in IF after
      chronic PD may shift the Starling equilibrium across peritoneal capillaries to an
      absorptive state.

PMID- 23152293
TI  - Effects of acute selective pudendal nerve electrical stimulation after simulated
      childbirth injury.
AB  - During childbirth, a combinatorial injury occurs and can result in stress urinary
      incontinence (SUI). Simulated childbirth injury, consisting of vaginal distension
      (VD) and pudendal nerve crush (PNC), results in slowed recovery of continence, as
      well as decreased expression of brain-derived neurotrophic factor (BDNF), a
      regenerative cytokine. Electrical stimulation has been shown to upregulate BDNF
      in motor neurons and facilitate axon regrowth through the increase of beta(II)
      tubulin expression after injury. In this study, female rats underwent selective
      pudendal nerve motor branch (PNMB) stimulation after simulated childbirth injury
      or sham injury to determine whether such stimulation affects bladder and anal
      function after injury and whether the stimulation increases BDNF expression in
      Onuf's nucleus after injury. Rats received 4 h of VD followed by bilateral PNC
      and 1 h of subthreshold electrical stimulation of the left PNMB and sham
      stimulation of the right PNMB. Rats underwent filling cystometry and anal
      pressure recording before, during, and after the stimulation. Bladder and anal
      contractile function were partially disrupted after injury. PNMB stimulation
      temporarily inhibited bladder contraction after injury. Two days and 1 wk after
      injury, BDNF expression in Onuf's nucleus of the stimulated side was
      significantly increased compared with the sham-stimulated side, whereas beta(II)
      tubulin expression in Onuf's nucleus of the stimulated side was significantly
      increased only 1 wk after injury. Acute electrical stimulation of the pudendal
      nerve proximal to the crush site upregulates BDNF and beta(II)-tubulin in Onuf's
      nucleus after simulated childbirth injury, which could be a potential preventive
      option for SUI after childbirth injury.

PMID- 23152295
TI  - Calcium reabsorption in the distal tubule: regulation by sodium, pH, and flow.
AB  - We developed a mathematical model of Ca(2+) transport along the late distal
      convoluted tubule (DCT2) and the connecting tubule (CNT) to investigate the
      mechanisms that regulate Ca(2+) reabsorption in the DCT2-CNT. The model accounts
      for apical Ca(2+) influx across transient receptor potential vanilloid 5 (TRPV5)
      channels and basolateral Ca(2+) efflux via plasma membrane Ca(2+)-ATPase pumps
      and type 1 Na(+)/Ca(2+) exchangers (NCX1). Model simulations reproduce
      experimentally observed variations in Ca(2+) uptake as a function of
      extracellular pH, Na(+), and Mg(2+) concentration. Our results indicate that
      amiloride enhances Ca(2+) reabsorption in the DCT2-CNT predominantly by
      increasing the driving force across NCX1, thereby stimulating Ca(2+) efflux. They
      also suggest that because aldosterone upregulates both apical and basolateral
      Na(+) transport pathways, it has a lesser impact on Ca(2+) reabsorption than
      amiloride. Conversely, the model predicts that full NCX1 inhibition and
      parathyroidectomy each augment the Ca(2+) load delivered to the collecting duct
      severalfold. In addition, our results suggest that regulation of TRPV5 activity
      by luminal pH has a small impact, per se, on transepithelial Ca(2+) fluxes; the
      reduction in Ca(2+) reabsorption induced by metabolic acidosis likely stems from
      decreases in TRPV5 expression. In contrast, elevations in luminal Ca(2+) are
      predicted to significantly decrease TRPV5 activity via the Ca(2+)-sensing
      receptor. Nevertheless, following the administration of furosemide, the calcium
      sensing receptor-mediated increase in Ca(2+) reabsorption in the DCT2-CNT is
      calculated to be insufficient to prevent hypercalciuria. Altogether, our model
      predicts complex interactions between calcium and sodium reabsorption in the DCT2
      CNT.

PMID- 23152296
TI  - Pirfenidone inhibits macrophage infiltration in 5/6 nephrectomized rats.
AB  - Tubulointerstitial macrophage infiltration is a hallmark of chronic kidney
      disease involved in the progression of renal fibrosis. Pirfenidone is a newly
      identified antifibrotic drug, the potential mechanism of which remains unclear.
      The aim of this study was to investigate the effects of pirfenidone on M1/M2
      macrophage infiltration in nephrectomized rats. Nephrectomized rats were treated
      with pirfenidone by gavage for 12 wk. Twenty-four hour urinary protein, N-acetyl
      beta-D-glycosaminidase (NAG) activity, systolic blood pressure, and C-reactive
      protein were determined. Paraffin-embedded sections were stained for CD68, CCR7,
      and CD163 macrophages. Monocyte chemoattractant protein-1 (MCP-1) and macrophage
      inflammatory protein-1alpha (MIP-1alpha), as well as M1 and M2 macrophages
      secretory markers, were evaluated by real-time RT-PCR and Western blotting
      analysis. Pirfenidone significantly improved the elevated proteinuria and NAG
      activity from week 2 onward after surgery. Pirfenidone attenuated interstitial
      fibrosis and decreased expression of fibrotic markers including transforming
      growth factor-beta(1), connective tissue growth factor, alpha-smooth muscle
      actin, fibronectin, and fibroblast-specific protein-1. Pirfenidone significantly
      decreased the infiltrating macrophages. The number of M1 and M2 macrophages was
      significantly lower after pirfenidone treatment. MCP-1 and MIP-1alpha were
      increased in nephrectomized rats at mRNA and protein levels. Pirfenidone
      treatment significantly inhibited their expression. The TNF-alpha, IL-6, and
      nitric oxide synthases-2 expressed by M1 macrophages were increased in
      nephrectomized rats, and pirfenidone significantly attenuated their expression.
      Pirfenidone treatment also significantly decreased arginase-1, dectin-1, CD206,
      and CD86 expressed by M2 macrophages. Thus pirfenidone inhibits M1 and M2
      macrophage infiltration in 5/6 nephrectomized rats, which suggests its efficacy
      in the early and late periods of renal fibrosis.

PMID- 23152297
TI  - An Af9 cis-element directly targets Dot1a to mediate transcriptional repression
      of the alphaENaC gene.
AB  - The epithelial Na(+) channel subunit-alpha (alphaENaC) of the distal nephron is
      essential for salt balance. We previously demonstrated that the histone
      methyltransferase Dot1a and its protein partner Af9 basally repress alphaENaC
      transcription in mouse inner medullary collecting duct type 3 (mIMCD3) cells and
      link aldosterone-elicited chromatin modifications to alphaENaC transcriptional
      activation. Af9 DNA-binding activity has never been demonstrated, and whether and
      where Af9 binds to the alphaENaC promoter to target Dot1a are unknown. The
      present study sought to identify functional Af9 cis-element(s) in the -57/+439
      "R3" subregion of alphaENaC, the principal site for Dot1a-Af9 interaction, in
      mIMCD3 cells. We also exploited connecting tubule/collecting duct-specific Dot1l
      deficient mice (Dot1l(AC)) to determine the impact of Dot1l inactivation on renal
      alphaENaC expression in vivo. mIMCD3 cell lines expressing alphaENaC promoter
      reporter constructs harboring deletion of +74/+107 demonstrated greatly reduced
      association of Af9 and Dot1a by ChIP/qPCR. Aldosterone treatment resulted in
      further decrements in Af9 and Dot1a association with the alphaENaC promoter. Gel
      shift and antibody competition assays using wild-type and mutant oligomers
      revealed Af9-containing +78/+92 alphaENaC DNA-protein complexes in nuclear
      extracts of mIMCD3 cells. Mutation of the +78/+92 element resulted in higher
      basal alphaENaC promoter activity and impaired Dot1a-mediated inhibition in trans
      repression assays. In agreement, mice with connecting tubule/collecting duct
      specific knockout of Dot1l exhibited greater alphaENaC mRNA levels in kidney
      compared with control. Thus, we conclude that +78/+92 of alphaENaC represents the
      primary Af9 binding site involved in recruiting Dot1a to repress basal and
      aldosterone-sensitive alphaENaC transcription and that Dot1l inactivation
      promotes alphaENaC mRNA expression by eliminating Dot1a-mediated repression.

PMID- 23152299
TI  - Neoadjuvant chemotherapy evaluation by MRI volumetry in rectal cancer followed by
      chemoradiation and total mesorectal excision: Initial experience.
AB  - PURPOSE: To evaluate rectal cancer volumetry in predicting initial neoadjuvant
      chemotherapy response. MATERIALS AND METHODS: Sixteen consecutive patients who
      underwent neoadjuvant chemotherapy (CX) before chemoradiotherapy (CRT) and
      surgery were enrolled in this retrospective study. Tumor volume was evaluated at
      the first magnetic resonance imaging (MRI), after CX and after CRT. Tumor volume
      regression (TVR) and downstaging were compared with histological results
      according to Tumor Regression Grade (TRG) to assess CX and CRT response,
      respectively. RESULTS: The mean tumor volume was 132 cm(3) +/- 166 before and 56
      cm(3) +/- 71 after CX. TVR after CX was significantly different between patients
      with poor histologic response (TRG1/2) and those with good histologic response
      (TRG3/4) (P = 0.001). An optimal cutoff of TVR >68% (area under the curve [AUC]:
      0.9, 95% confidence interval [CI]: 0.65-0.98, P = 0.0001) to predict good
      histology response after CX was assessed by receiver operating characteristic
      curve. According to previous data and this study, we defined 70% as the best
      cutoff values according to sensitivity (86%), specificity (100%) of TVR for
      predicting good histology response. In contradistinction, MRI downstaging was
      associated with TRG only after CRT (P = 0.04). CONCLUSION: Our pilot study showed
      that MRI volumetry can predict early histological response after CX and before
      CRT. MRI volumetry could help the clinician to distinguish early responders in
      order to aid appropriate individually tailored therapies.

PMID- 23152298
TI  - Upregulation of soluble epoxide hydrolase in proximal tubular cells mediated
      proteinuria-induced renal damage.
AB  - Epoxyeicosatrienoic acids, hydrolyzed by soluble epoxide hydrolase (sEH), have
      multiple biological functions, including the regulation of vascular tone, renal
      tubular transport, and being anti-inflammatory. Inhibitors of sEH have been
      demonstrated to be antihypertensive and renal protective. To elucidate the role
      of sEH in glomerulonephritis, we first determined the expression of sEH in human
      kidney by examining biopsies from 153 patients with a variety of
      glomerulonephritis, including minimal-change, membranous, and IgA nephropathy.
      Immunohistochemical staining of frozen kidney biopsy samples revealed sEH
      preferentially expressed in the renal proximal tubular cells, and its expression
      increased in all patients with glomerulonephritis. The level of sEH in the cortex
      was positively correlated with proteinuria and negatively with serum albumin
      level. To investigate the role of sEH in proteinuria-induced renal damage, we
      incubated purified urine protein from patients with rat renal proximal tubular
      epithelial cells in vitro. The level of sEH was elevated, as were monocyte
      chemoattractant protein 1 and the process of tubular epithelial-to-mesenchymal
      transition, characterized with increased alpha-smooth muscle actin (alpha-SMA)
      and decreased E-cadherin. These effects were attenuated by administration of a
      potent sEH inhibitor and mimicked with adenovirus-mediated sEH overexpression. In
      adriamycin-induced nephropathic mice, sEH inhibitor did not ameliorate
      proteinuria or level of serum albumin but reduced the long-term elevated serum
      creatinine level, interstitial inflammation, fibrosis, and alpha-SMA expression.
      Thus upregulation of sEH in proximal tubular cells in chronic proteinuric kidney
      diseases may mediate proteinuria-induced renal damage; sEH inhibition by
      increasing renal eicosanoid levels could prevent the progression of chronic
      proteinuric kidney diseases.

PMID- 23152300
TI  - Delayed leptin administration after stroke induces neurogenesis and angiogenesis.
AB  - Leptin is a potent AMP kinase (AMPK) inhibitor that induces neuroprotection,
      neurogenesis, and angiogenesis when administered immediately after stroke. To
      dissociate these effects, we explored the effects of delayed administration of
      leptin, at 10 days after stroke onset, on neurogenesis and angiogenesis after
      stroke. Sabra mice underwent photothrombotic stroke and were treated with vehicle
      or leptin given either as a single dose or in triple dosing, 10 days later.
      Newborn cells were labeled with bromodeoxyuridine. Functional outcome was studied
      with the neurological severity score for 90 days poststroke, and the brains were
      then evaluated via immunohistochemistry. Final infarct volumes did not differ
      between the groups. Exogenous leptin led to significant increments in the number
      of proliferating BrdU(+) cells in the subventricular zone and in the cortex
      abutting the lesion (2.5-fold and 1.4-fold, respectively). There were significant
      increments in the number of newborn neurons and glia (4- and 3.4-fold,
      respectively) in leptin-treated animals. Leptin also significantly increased the
      number of blood vessels in the perilesioned cortex. However, animals treated with
      leptin failed to demonstrate significantly better functional states. In
      conclusion, leptin induces neurogenesis and angiogenesis even when given late
      after stroke but does not lead to better functional outcome in this delayed
      treatment paradigm. These results suggest that the main beneficial effects of
      leptin after stroke are associated with its early neuroprotective role rather
      than with its proneurogenic or proangiogenic effects.

PMID- 23152301
TI  - Immunohistochemical detection of the putative mechanoproteins ASIC2 and TRPV4 in
      avian herbst sensory corpuscles.
AB  - The avian Herbst corpuscles are the equivalent of the Pacinian corpuscles in
      mammals, and detect vibration and the movement of joints and feathers. Therefore,
      they can be regarded as rapidly adapting low-threshold mechanoreceptors. In
      recent years, it has been establish that some ion channels are involved in
      mechanosensation and are present in both mechanosensory neurons and
      mechanoreceptors. Here we have used immunohistochemistry to localize some
      putative mechanoproteins in the Herbst corpuscles from the rictus of Columba
      livia. The proteins investigated were the subunits of the epithelial Na(+)
      channel (ENaC), the transient-receptor potential vanilloid 4 (TRPV4), and the
      acid-sensing ion channel 2 (ASIC2). Immunoreactivity for ENaC subunits was never
      found in Herbst corpuscles, while the axon expressed ASIC2 and TRPV4
      immunoreactivity. Moreover, TRPV4 was also detected in the cell forming the inner
      core. The present results demonstrate for the first time the occurrence of
      mechanoproteins in avian low-threshold mechanoreceptors and provide further
      evidence for a possible role of the ion channels in mechanosensation.

PMID- 23152302
TI  - Columnar distribution of catecholaminergic neurons in the ventrolateral
      periaqueductal gray and their relationship to efferent pathways.
AB  - The periaqueductal gray (PAG) is a critical brain region involved in opioid
      analgesia and provides efferents to descending pathways that modulate
      nociception. In addition, the PAG contains ascending pathways to regions involved
      in the regulation of reward, including the substantia nigra (SN) and the ventral
      tegmental area (VTA). SN and VTA contain dopaminergic neurons that are critical
      for the maintenance of positive reinforcement. Interestingly, the PAG is also
      reported to contain a population of dopaminergic neurons. In this study, the
      distribution of catecholaminergic neurons within the ventrolateral (vl) PAG was
      examined using immunocytochemical methods. In addition, the catecholaminergic PAG
      neurons were examined to determine whether these neurons are integrated into
      ascending (VTA, SN) and descending rostral ventral medulla (RVM) efferent
      pathways from this region. The immunocytochemical analysis determined that
      catecholaminergic neurons in the PAG are both dopaminergic and noradrenergic and
      these neurons have a distinct rostrocaudal distribution within the ventrolateral
      column of PAG. Dopaminergic neurons were concentrated rostrally and were
      significantly smaller than noradrenergic neurons. Combined immunocytochemistry
      and tract tracing methods revealed that catecholaminergic neurons are distinct
      from, but closely associated with, both ascending and descending efferent
      projection neurons. Finally, by electron microscopy, catecholaminergic neurons
      showed close dendritic appositions with other neurons in PAG, suggesting a
      possible nonsynaptic mechanism for regulation of PAG output by these neurons. In
      conclusion, our data indicate that there are two populations of catecholaminergic
      neurons in the vlPAG that form dendritic associations with both ascending and
      descending efferents suggesting a possible nonsynaptic modulation of vlPAG
      neurons.

PMID- 23152303
TI  - Reverse transcription loop-mediated isothermal amplification for rapid detection
      of the newly emerged poultry Flavivirus.
AB  - Poultry Flavivirus (PF) was a recently emerged virus with high morbidity rates
      and mortality rates in China. It is the causative agent of egg drop syndrome at
      present. Development of the reverse transcription loop-mediated isothermal
      amplification (RT-LAMP) assay was the most efficient way to prevent and control
      the PF disease. The assay was performed at 64  degrees C for 45 min, using six
      specific primers that recognized eight targets of the PF E gene. The RT-LAMP
      assay, compared to conventional reverse transcription polymerase chain reaction,
      has 100-fold-greater sensitivity, with a detection limit of 1 * 10(-3) copies per
      MUL RNA and no cross-reaction with poultry other viruses. The RT-LAMP assay is a
      valuable tool for detected PF without requiring any sophisticated equipment, and
      the detection has potential usefulness for clinical diagnosis in the field.

PMID- 23152304
TI  - Early hematopoietic stem cell transplant is associated with favorable outcomes in
      children with MDS.
AB  - BACKGROUND: Although hematopoietic stem cell transplantation (HSCT) is the
      treatment of choice for childhood myelodysplastic syndrome (MDS), there is no
      consensus regarding patient or disease characteristics that predict outcomes.
      PROCEDURE: We reviewed 37 consecutive pediatric MDS patients who received
      myeloablative HSCT between 1990 and 2010 at a single center. RESULTS: Twenty had
      primary MDS and 17 had secondary MDS. Diagnostic cytogenetics included monosomy 7
      (n = 21), trisomy 8 (n = 7) or normal/other (n = 8). According to the modified
      WHO MDS classification, thirty had refractory cytopenia and seven had refractory
      anemia with excess blasts. IPSS scores were: low risk (n = 1), intermediate-1 (n
      = 15), and intermediate-2 (n = 21). OS and DFS at 10 years in the entire cohort
      was 53% and 45%. Relapse at 10 years was 26% and 1 year TRM was 25%. In
      multivariate analysis, factors associated with improved 3 years DFS were not
      receiving pre-HSCT chemotherapy (RR = 0.30, 95% CI 0.10-0.88; P = 0.03) and a
      shorter interval (<140 days) from time of diagnosis to transplant (RR = 0.27, 95%
      CI 0.09-0.80; P = 0.02). Three years DFS in patients who did not receive pre-HSCT
      chemotherapy and those who had a shorter interval to transplant (n = 16) was 80%.
      CONCLUSION: These results suggest that children with MDS should be referred for
      allogeneic HSCT soon after diagnosis and that pre-HSCT chemotherapy does not
      appear to improve outcomes.

PMID- 23152305
TI  - Successful treatment of cerebral venous sinus thrombosis with the Solitaire FR
      thrombectomy device.
AB  - A young woman with factor V Leiden thrombophilia presented with headache due to
      thrombosis of the right transverse sinus (TS) and superior sagittal sinus.
      Despite appropriate anticoagulation, she experienced worsening headache,
      progressive neurologic deficits and spontaneous subarachnoid hemorrhage.
      Endovascular therapy was therefore undertaken. A 6 mm Solitaire FR device was
      deployed in the TS and withdrawn in a stepwise fashion, resulting in complete
      recanalization of the sinus. Her headache improved and her neurologic deficits
      resolved. Endovascular therapy for cerebral venous sinus thrombosis is currently
      recommended only for those patients with deterioration despite appropriate
      anticoagulation. The thrombus burden is usually high in this subset of patients,
      and recanalization can be challenging with currently available endovascular
      techniques. This is the first report of cerebral venous sinus thrombectomy with
      the Solitaire FR device, which may offer another option for those patients
      requiring endovascular treatment.

PMID- 23152306
TI  - Carotenoid content of wild edible young shoots traditionally consumed in Spain
      (Asparagus acutifolius L., Humulus lupulus L., Bryonia dioica Jacq. and Tamus
      communis L.).
AB  - BACKGROUND: Wild vegetables have traditionally been consumed as part of the
      Mediterranean diet, being valuable sources of nutrients and bioactive compounds.
      The objective of this work was to analyse the carotenoid content of the edible
      young shoots of four species (Asparagus acutifolius L., Humulus lupulus L.,
      Bryonia dioica Jacq. and Tamus communis L.) as part of a wider study on the
      characterisation of the nutritional composition of wild edible plants commonly
      consumed in Spain. Samples were gathered from two locations in Central Spain for
      two consecutive years. RESULTS: Lutein, beta-carotene, neoxanthin and
      violaxanthin were quantified by high-performance liquid chromatography with a
      photodiode array detector. Median concentration ranges (MUg g(-1) edible wet
      weight) were: beta-carotene, 3.39-6.69, lutein, 5.44-19.13;neoxanthin, 5.17
      17.37; and violaxanthin, 2.08-8.93. The highest carotenoid content was that of B.
      dioica (59.01 MUg g(-1)) and the lowest was found in A. acutifolius (17.58 MUg g(
      1)) [corrected]. CONCLUSION: Our results show that these wild young shoots are
      richer sources of carotenoids than many of the commercially available leafy
      vegetables.

PMID- 23152307
TI  - Corticomedullary differentiation of the kidney: evaluation with noncontrast
      enhanced steady-state free precession (SSFP) MRI with time-spatial labeling
      inversion pulse (time-SLIP).
AB  - PURPOSE: To assess whether noncontrast-enhanced steady-state free precession
      (SSFP) magnetic resonance imaging (MRI) with time-spatial labeling inversion
      pulse (Time-SLIP) can improve the visibility of corticomedullary differentiation
      of the normal kidney. MATERIALS AND METHODS: A series of noncontrast-enhanced
      SSFP MRI with Time-SLIP were performed in 20 patients by using various inversion
      times (TIs); 500-1800 msec in increments of 100 msec. In-phase (IP) and opposed
      phase (OP) MR images were also obtained. The signal intensity (SI) of the renal
      cortex and medulla was measured to calculate corticomedullary contrast ratio (SI
      of cortex/medulla). Additionally, the visibility of corticomedullary
      differentiation was visually categorized using a four-point scale. RESULTS: In
      SSFP with Time-SLIP, corticomedullary contrast ratio was highest with TI of 1200
      msec in eight subjects (40%), followed by 1100 msec in seven (35%) and 1000 msec
      in three (15%). The corticomedullary contrast ratio in SSFP with optimal Time
      SLIP (4.93 +/- 1.25) was significantly higher (P < 0.001) than those of IP (1.46
      +/- 0.12) and OP (1.43 +/- 0.14). The visibility of corticomedullary
      differentiation was significantly better (P < 0.001) in SSFP images with Time
      SLIP (averaged grade = 4.0) than in IP images (averaged grade = 2.63) and OP
      images (averaged grade = 2.05). CONCLUSION: SSFP MRI with Time-SLIP can improve
      the visibility of renal corticomedullary differentiation without using contrast
      agents.

PMID- 23152308
TI  - Somal and dendritic development of human CA3 pyramidal neurons from midgestation
      to middle childhood: a quantitative Golgi study.
AB  - The CA3 area serves a key relay on the tri-synaptic loop of the hippocampal
      formation which supports multiple forms of mnemonic processing, especially
      spatial learning and memory. To date, morphometric data about human CA3 pyramidal
      neurons are relatively rare, with little information available for their pre- and
      postnatal development. Herein, we report a set of developmental trajectory data,
      including somal growth, dendritic elongation and branching, and spine formation,
      of human CA3 pyramidal neurons from midgestation stage to middle childhood. Golgi
      impregnated CA3 pyramidal neurons in fetuses at 19, 20, 26, 35, and 38 weeks of
      gestation (GW) and a child at 8 years of age (Y) were analyzed by Neurolucida
      morphometry. Somal size of the impregnated CA3 cells increased age-dependently
      among the cases. The length of the apical and basal dendrites of these neurons
      increased between 26 GW to 38 GW, and appeared to remain stable afterward until 8
      Y. Dendritic branching points increased from 26 GW to 38 GW, with that on the
      apical dendrites slightly reduced at 8 Y. Spine density on the apical and basal
      dendrites increased progressively from 26 GW to 8 Y. These data suggest that
      somal growth and dendritic arborization of human CA3 pyramidal neurons occur
      largely during the second to third trimester. Spine development and likely
      synaptogenesis on CA3 pyramidal cells progress during the third prenatal
      trimester and may continue throughout childhood.

PMID- 23152309
TI  - Effect of polysorbate 80 concentration on thermal and photostability of a
      monoclonal antibody.
AB  - Polysorbate 80 is widely used in protein formulations to protect protein against
      agitation-induced aggregation. In this study, we address concerns about residual
      peroxide present in Polysorbate 80 on protein stability. Residual peroxide may
      oxidize active pharmaceutical ingredients leading to reduced stability and may
      ultimately lead to lower potency and efficacy. The effect of Polysorbate 80
      concentration on thermal and photostability of monoclonal antibody of the IgG1
      subclass (MAb1) was evaluated at Polysorbate 80 concentrations ranging from 0.00%
      to 1.00% (w/v). MAb1 samples at 5 mg/mL with various Polysorbate 80
      concentrations were subjected to accelerated thermal stress by incubation at 25
      degrees C, 40 degrees C, and 50 degrees C for a period of 4 weeks and light
      stress per ICH guideline Q1B, option 1. Our results show that Polysorbate 80
      concentration of 1.00% (w/v) adversely affected thermal and photostability of
      MAb1. This study demonstrates the importance of carefully choosing Polysorbate 80
      concentration in protein formulations to prevent destabilizing effect of
      Polysorbate 80 on thermal and photostability.

PMID- 23152310
TI  - Molecular characterization of Aeromonas spp. and Vibrio cholerae O1 isolated
      during a diarrhea outbreak.
AB  - This work aimed to assess pathogenic potential and clonal relatedness of
      Aeromonas sp. and Vibrio cholerae isolates recovered during a diarrhea outbreak
      in Brazil. Clinical and environmental isolates were investigated for the presence
      of known pathogenic genes and clonal relatedness was assessed by intergenic
      spacer region (ISR) 16S-23S amplification. Four Aeromonas genes (lip, exu, gcat,
      flaA/B) were found at high overall frequency in both clinical and environmental
      isolates although the lip gene was specifically absent from selected species. A
      fifth gene, aerA, was rarely found in A. caviae, the most abundant species. The
      ISR profile revealed high heterogeneity among the Aeromonas isolates and no
      correlation with species identification. In contrast, in all the V. cholerae
      isolates the four genes investigated (ctxA, tcpA, zot and ace) were amplified and
      revealed homogeneous ISR and RAPD profiles. Although Aeromonas isolates were the
      major enteric pathogen recovered, their ISR profiles are not compatible with a
      unique cause for the diarrhea events, while the clonal relationship clearly
      implicates V. cholerae in those cases from which it was isolated. These results
      reinforce the need for a better definition of the role of aeromonads in diarrhea
      and whether they benefit from co-infection with V. cholerae.

PMID- 23152311
TI  - Comparison of five methods for oxacillin susceptibility testing of Staphylococcus
      aureus isolates from cystic fibrosis patients.
AB  - Methicillin-resistant Staphylococcus aureus (MRSA) are now a worldwide problem.
      Cystic fibrosis (CF) patients are commonly colonized and infected by MRSA.
      Accurate oxacillin susceptibility testing is mandatory for the adequate
      management of these patients. We performed a comparison of the accuracy of
      different tests in CF isolates, including methicillin-susceptible S. aureus and
      MRSA with different SCCmec types, and using the mecA gene as the gold-standard.
      The sensitivity and specificity of oxacillin disc, Etest, and oxacillin agar
      screening plate were 100%. Sensitivity of the cefoxitin disc was 85% and
      specificity was 100%. For clinically relevant isolates, laboratories may consider
      the use of a combination of two phenotypic methods.

PMID- 23152312
TI  - Frequency of human bocavirus respiratory infections among at-risk patients in Sao
      Paulo, Brazil.
AB  - BACKGROUND AND OBJECTIVES: Human Bocavirus (HBoV) has been described since 2005
      as an etiological agent of respiratory virus infections. From 2001 to 2008 we
      investigated the etiology of HBoV among adults and children in different groups
      at risk of presenting complications arising from acute respiratory infection, the
      investigation was carried out in a tertiary hospital health care system in
      Brazil. METHODS: HBoV DNA was assayed in 598 respiratory samples from community
      and hospitalized patients by PCR. RESULTS: Of the 598 tested samples, 2.44%
      (8/328) of children, including five children with heart disease, and 0.4% (1/270)
      of adult bone-marrow-transplant were HBoV positive. CONCLUSIONS: These data
      suggested lower HBoV frequency among different at-risk patients and highlights
      the need to better understand the real role of HBoV among acute respiratory
      symptomatic patients.

PMID- 23152313
TI  - Influenza viruses in adult dogs raised in rural and urban areas in the state of
      Sao Paulo, Brazil.
AB  - In 1970, searching for the interspecies transmission of influenza viruses led to
      the first study on influenza viruses in domestic animals. Birds and mammals,
      including human beings, are their natural hosts; however, other animals may also
      play a role in the virus epidemiology. The objective was to investigate the
      incidence of influenza viruses in adult dogs raised in rural (9, 19.56%) and
      urban (37, 80.43%) areas in the state of Sao Paulo, Brazil. Dog serum samples
      were examined for antibodies to influenza viruses by the hemagglutination
      inhibition (HI) test using the corresponding antigens from the circulating
      viruses in Brazil. Dogs from rural areas presented antibodies to influenza A
      H3N2, and influenza A H7N7 and H3N8. In rural areas, dog sera displayed mean
      titers as 94.37, 227.88, 168.14, 189.62 HIU/25 uL for subtypes H1N1, H3N2, H7N7,
      H3N8, respectively. About 84% and 92% of dogs from urban areas exhibited
      antibodies to human influenza A H1N1 and H3N2, respectively, with statistical
      difference at p < 0.05 between the mean titers of antibodies to H1N1 and H3N2.
      About 92% and 100% were positive for H7N7 and H3N8, respectively. In dogs from
      urban areas, the mean titers of antibodies against influenza A H1N1, H3N2, H7N7
      and H3N8, were 213.96, 179.42, 231.76, 231.35 HIU/25 uL respectively. The
      difference among them was not statistically significant at p > 0.05. In
      conclusion, these dogs were positive for both human and equine influenza viruses.
      The present study suggests the first evidence that influenza viruses circulate
      among dogs in Brazil.

PMID- 23152314
TI  - Lagochilascaris minor Leiper, 1909 (Nematoda: Ascarididae) in Mexico: three
      clinical cases from the Peninsula of Yucatan.
AB  - Human lagochilascariasis (HL) is a parasite produced by Lagochilascaris minor
      Leiper 1909 that also can be found in cats and dogs. HL is considered an emerging
      zoonosis in the Americas, spreading from Mexico to Argentina, and the Caribbean
      Islands. The present paper describes three HL cases from the Peninsula of
      Yucatan, Mexico, recorded in the last decade. It describes the characteristics of
      the lesions and discusses the route of transmission in humans and particularly in
      the observed patients.

PMID- 23152315
TI  - The close relationship between toxoplasmosis and kidney function.

PMID- 23152316
TI  - Effects of vitamin C supplementation on acute phase Chagas disease in
      experimentally infected mice with Trypanosoma cruzi QM1 strain.
AB  - The tissue changes that occur in Chagas disease are related to the degree of
      oxidative stress and antioxidant capacity of affected tissue. Studies with
      vitamin C supplementation did not develop oxidative damage caused by Chagas
      disease in the host, but other studies cite the use of peroxiredoxins ascorbate -
      dependent on T. cruzi to offer protection against immune reaction. Based on these
      propositions, thirty "Swiss" mice were infected with T. cruzi QM1 strain and
      treated with two different vitamin C doses in order to study the parasitemia
      evolution, histopathological changes and lipid peroxidation biomarkers during the
      acute phase of Chagas disease. The results showed that the parasite clearance was
      greater in animals fed with vitamin C overdose. There were no significant
      differences regarding the biomarkers of lipid peroxidation and inflammatory
      process or the increase of myocardium in animals treated with the recommended
      dosage. The largest amount of parasite growth towards the end of the acute phase
      suggests the benefit of high doses of vitamin C for trypomastigotes. The
      supplementation doesn't influence the production of free radicals or the number
      of amastigote nests in the acute phase of Chagas disease.

PMID- 23152317
TI  - Low genetic diversity in Wolbachia-Infected Culex quinquefasciatus (Diptera:
      Culicidae) from Brazil and Argentina.
AB  - Culex quinquefasciatus is a vector of human pathogens, including filarial
      nematodes and several viruses. Although its epidemiological relevance is known to
      vary across geographical regions, an understanding of its population genetic
      structure is still incipient. In light of this, we evaluated the genetic
      diversity of Cx. quinquefasciatus and Cx. pipiens x Cx. quinquefasciatus hybrids
      collected from nine localities in Brazil and one site in Argentina. We used
      mitochondrial genes cox1 and nd4, along with the coxA and wsp genes of the
      maternally-inherited Wolbachia endosymbiont. The nd4 fragment was invariant
      between samples, whilst cox1 exhibited four haplotypes that separated two types
      of Cx. quinquefasciatus, one clustered in southern Brazil. Low sequence diversity
      was generally observed, being discussed. Both Brazilian and Argentinian
      mosquitoes were infected with a single Wolbachia strain. As reported in previous
      studies with these populations, cox1 and nd4 diversity is not congruent with the
      population structure revealed by nuclear markers or alar morphology. Future Cx.
      quinquefasciatus research should, if possible, evaluate mtDNA diversity in light
      of other markers.

PMID- 23152318
TI  - Analogies in medicine: marine pilot's wheel.

PMID- 23152319
TI  - Brazilian mosquito (Diptera: Culicidae) fauna: I. Anopheles species from Porto
      Velho, Rondonia state, western Amazon, Brazil.
AB  - This study contributes to knowledge of Anopheles species, including vectors of
      Plasmodium from the western Brazilian Amazon in Porto Velho, Rondonia State. The
      sampling area has undergone substantial environmental changes as a consequence of
      agricultural and hydroelectric projects, which have caused intensive
      deforestation and favored habitats for some mosquito species. The purpose of this
      study was to diagnose the occurrence of anopheline species from collections in
      three locations along an electric-power transmission line. Each locality was
      sampled three times from 2010 to 2011. The principal adult mosquitoes captured in
      Shannon trap were Anopheles darlingi, An. triannulatus, An. nuneztovari l.s.,
      An.gilesi and An. costai. In addition, larvae were collected in ground breeding
      sites for Anopheles braziliensis, An. triannulatus, An. darlingi, An. deaneorum,
      An. marajoara, An. peryassui, An. nuneztovari l.s. and An. oswaldoi-konderi.
      Anopheles darlingi was the most common mosquito in the region. We discuss
      Culicidae systematics, fauna distribution, and aspects of malaria in altered
      habitats of the western Amazon.

PMID- 23152320
TI  - Toxicity of saponin isolated from Gymnema sylvestre R. Br. (Asclepiadaceae)
      against Culex tritaeniorhynchus Giles (Diptera: Culicidae) Japanese encephalitis
      vector mosquito in India.
AB  - To determine the larvicidal activity of various extracts of Gymnema sylvestre
      against the Japanese Encephalitis vector, Culex tritaeniorynchus in Tamilnadu,
      India. To identify the active principle present in the promising fraction
      obtained in Chlorofom:Methanol extract of Fraction 2. The G. sylvestre leaf
      extracts were tested, employing WHO procedure against fourth instar larvae of C.
      tritaeniorhynchus and the larval mortalities were recorded at various
      concentrations (6.25, 12.5, 25.0, 50 and 100 ug/mL); the 24h LC50 values of the
      G. Sylvestre leaf extracts were determined following Probit analysis. It was
      noteworthy that treatment level 100 ug/mL exhibited highest mortality rates for
      the three different crude extracts and was significantly different from the mean
      mortalities recorded for the other concentrations. The LC50 values of 34.756
      ug/mL (24.475-51.41), 31.351 ug/mL (20.634-47.043) and 28.577 ug/mL (25.159
      32.308) were calculated for acetone, chloroform and methanol extract with the chi
      square values of 10.301, 31.351 and 4.093 respectively. The present investigation
      proved that G. Sylvestre could be possibly utilized as an important component in
      the Vector Control Program.

PMID- 23152321
TI  - Anal squamous carcinoma: a new AIDS-defining cancer? Case report and literature
      review.
AB  - Squamous anal cell carcinoma is a rare malignancy that represents the 1.5% to 2%
      of all the lower digestive tract cancers. However, an increased incidence of
      invasive anal carcinoma is observed in HIV-seropositive population since the
      widespread of highly active antiretroviral therapy. Human papillomavirus is
      strongly associated with the pathogenesis of anal cancer. Anal intercourse and a
      high number of sexual partners appear to be risk factors to develop anal cancer
      in both sexes. Anal pain, bleeding and a palpable lesion in the anal canal are
      the most common clinical features. Endo-anal ultrasound is the best diagnosis
      method to evaluate the tumor size, the tumor extension and the infiltration of
      the sphincter muscle complex. Chemoradiotherapy plus antiretroviral therapy are
      the recommended treatments for all stages of localized squamous cell carcinoma of
      the anal canal in HIV-seropositive patients because of its high rate of cure.
      Here we present an HIV patient who developed a carcinoma of the anal canal after
      a long time of HIV infection under highly active antiretroviral therapy with a
      good virological and immunological response.

PMID- 23152322
TI  - Successful liver transplantation in an infant with stage 4S(M) neuroblastoma.
AB  - We report a 2.5-month-old infant with bilateral adrenal neuroblastoma, stage
      4S(M), with liver metastases and chemotherapy-induced veno-occlusive disease
      leading to cirrhosis requiring liver transplantation. Despite unknown tumour
      histology and MYCN-amplification status, we proceeded with liver transplant. This
      decision was based on clinical suspicion that our patient was MYCN-negative due
      to significant tumour regression, and was supported by evidence indicating that
      MYCN-amplification is rare in infants with favourable-stage neuroblastoma. This
      is the second case report of neuroblastoma requiring liver transplantation;
      however, in the previously reported case, the diagnosis of neuroblastoma was not
      established until after transplantation. We discuss this unique case to justify
      the potential use of life-saving liver transplants in infants with neuroblastoma.

PMID- 23152323
TI  - What is the greatest regulatory challenge in the translation of biomaterials to
      the clinic?
AB  - Leaders in the field comment on what they perceive to be the greatest barriers to
      biomaterial translation.

PMID- 23152324
TI  - Regenerative engineering.

PMID- 23152326
TI  - Dynamic microenvironments: the fourth dimension.
AB  - The extracellular space, or cell microenvironment, choreographs cell behavior
      through myriad controlled signals, and aberrant cues can result in dysfunction
      and disease. For functional studies of human cell biology or expansion and
      delivery of cells for therapeutic purposes, scientists must decipher this
      intricate map of microenvironment biology and develop ways to mimic these
      functions in vitro. In this Perspective, we describe technologies for four
      dimensional (4D) biology: cell-laden matrices engineered to recapitulate tissue
      and organ function in 3D space and over time.

PMID- 23152325
TI  - Building vascular networks.
AB  - Only a few engineered tissues-skin, cartilage, bladder-have achieved clinical
      success, and biomaterials designed to replace more complex organs are still far
      from commercial availability. This gap exists in part because biomaterials lack a
      vascular network to transfer the oxygen and nutrients necessary for survival and
      integration after transplantation. Thus, generation of a functional vasculature
      is essential to the clinical success of engineered tissue constructs and remains
      a key challenge for regenerative medicine. In this Perspective, we discuss recent
      advances in vascularization of biomaterials through the use of biochemical
      modification, exogenous cells, or microengineering technology.

PMID- 23152327
TI  - Engineering complex tissues.
AB  - Tissue engineering has emerged at the intersection of numerous disciplines to
      meet a global clinical need for technologies to promote the regeneration of
      functional living tissues and organs. The complexity of many tissues and organs,
      coupled with confounding factors that may be associated with the injury or
      disease underlying the need for repair, is a challenge to traditional engineering
      approaches. Biomaterials, cells, and other factors are needed to design these
      constructs, but not all tissues are created equal. Flat tissues (skin); tubular
      structures (urethra); hollow, nontubular, viscus organs (vagina); and complex
      solid organs (liver) all present unique challenges in tissue engineering. This
      review highlights advances in tissue engineering technologies to enable
      regeneration of complex tissues and organs and to discuss how such innovative,
      engineered tissues can affect the clinic.

PMID- 23152328
TI  - Designing regenerative biomaterial therapies for the clinic.
AB  - The ability to regenerate damaged tissue is one of the great challenges in
      biomaterials and medicine. Successful treatments will require advances in areas
      ranging from basic cell biology to materials synthesis, but there have been major
      hurdles in translating the biomedical advances, such as scaffolds that direct
      stem cell differentiation, into marketed products. Careful consideration of the
      challenges going from bench to bedside is paramount in maximizing the chances
      that a good idea becomes a good treatment. We look at a variety of material-based
      platforms that have made it into the clinic, from biodegradable polymers for
      wound healing to organs grown ex vivo, and how they have been able to navigate
      the scientific, regulatory, and business hurdles into the market place.

PMID- 23152329
TI  - Compromised cerebrovascular modulation in chronic anxiety: evidence from cerebral
      blood flow velocity measured by transcranial Doppler sonography.
AB  - OBJECTIVE: Cerebral autoregulation (CA) is the mechanism by which constant
      cerebral blood flow is maintained despite changes in cerebral perfusion pressure.
      CA can be evaluated by dynamic monitoring of cerebral blood flow velocity (CBFV)
      with transcranial Doppler sonography (TCD). The present study aimed to explore CA
      in chronic anxiety. METHODS: Subjects with Hamilton anxiety scale scores >=14
      were enrolled and the dynamic changes of CBFV in response to an orthostatic
      challenge were investigated using TCD. RESULTS: In both the anxious and the
      healthy subjects, the mean CBFV was significantly lower in the upright position
      than when supine. However, the CBFV changes from supine to upright differed
      between the anxious and the healthy groups. Anxious subjects showed more
      pronounced decreases in CBFV with abrupt standing. CONCLUSION: Our results
      indicate that cerebrovascular modulation is compromised in chronic anxiety;
      anxious subjects have some insufficiency in maintaining cerebral perfusion after
      postural change. Given the fact that anxiety and impaired CA are associated with
      cardiovascular disease, early ascertainment of compromised cerebrovascular
      modulation using TCD might suggest interventional therapies in the anxious
      population, and improve the primary prevention of cardiovascular disease.

PMID- 23152331
TI  - Brassinosteroid control of shoot gravitropism interacts with ethylene and depends
      on auxin signaling components.
AB  - PREMISE OF THE STUDY: To reach favorable conditions for photosynthesis, seedlings
      grow upward when deprived of light upon underground germination. To direct their
      growth, they use their negative gravitropic capacity. Negative gravitropism is
      under tight control of multiple hormones. METHODS: By counting the number of
      standing plants in a population or by real time monitoring of the reorientation
      of gravistimulated seedlings of Arabidopsis thaliana, we evaluated the negative
      gravitropism of ethylene or brassinosteroid (BR) treated plants. Meta-analysis of
      transcriptomic data on AUX/IAA genes was gathered, and subsequent mutant analysis
      was performed. KEY RESULTS: Ethylene and BR have opposite effects in regulating
      shoot gravitropism. Lack of BR enhances gravitropic reorientation in 2-d-old
      seedlings, whereas ethylene does not. Lack of ethylene signaling results in
      enhanced BR sensitivity. Ethylene and BRs regulate overlapping sets of AUX/IAA
      genes. BRs regulate a wider range of auxin signaling components than ethylene.
      CONCLUSIONS: Upward growth in seedlings depends strongly on the internal hormonal
      balance. Endogenous ethylene stimulates, whereas BRs reduce negative gravitropism
      in a manner that depends on the function of different, yet overlapping sets of
      auxin signaling components.

PMID- 23152332
TI  - Phototropism: translating light into directional growth.
AB  - Phototropism allows plants to align their photosynthetic tissues with incoming
      light. The direction of incident light is sensed by the phototropin family of
      blue light photoreceptors (phot1 and phot2 in Arabidopsis), which are light
      activated protein kinases. The kinase activity of phototropins and
      phosphorylation of residues in the activation loop of their kinase domains are
      essential for the phototropic response. These initial steps trigger the formation
      of the auxin gradient across the hypocotyl that leads to asymmetric growth. The
      molecular events between photoreceptor activation and the growth response are
      only starting to be elucidated. In this review, we discuss the major steps
      leading from light perception to directional growth concentrating on Arabidopsis.
      In addition, we highlight links that connect these different steps enabling the
      phototropic response.

PMID- 23152330
TI  - Phosphoinositide pathway and the signal transduction network in neural
      development.
AB  - The development of the nervous system is under the strict control of a number of
      signal transduction pathways, often interconnected. Among them, the
      phosphoinositide (PI) pathway and the related phospholipase C (PI-PLC) family of
      enzymes have been attracting much attention. Besides their well-known role in the
      regulation of intracellular calcium levels, PI-PLC enzymes interact with a number
      of molecules belonging to further signal transduction pathways, contributing to a
      specific and complex network in the developing nervous system. In this review,
      the connections of PI signalling with further transduction pathways acting during
      neural development are discussed, with special regard to the role of the PI-PLC
      family of enzymes.

PMID- 23152333
TI  - Ventilator-associated pneumonia and oral health.

PMID- 23152334
TI  - Immunopathogenesis and neurological manifestations associated to HTLV-1
      infection.
AB  - The human T lymphotropic virus type-1 (HTLV-1) was the first human retrovirus
      identified. The virus is transmitted through sexual intercourse, blood
      transfusion, sharing of contaminated needles or syringes and from mother to
      child, mainly through breastfeeding. In addition to the well-known association
      between HTLV-1 and HTLV-1-associated myelopathy/tropical spastic paraparesis
      (HAM/TSP), several diseases and neurologic manifestations have been associated
      with the virus. This review was conducted through a PubMed search of the terms
      HTLV-1, immune response and neurological diseases. Emphasis was given to the most
      recent data regarding pathogenesis and clinical manifestations of HTLV-1
      infection. The aim of the review is to analyze the immune response and the
      variety of neurological manifestations associated to HTLV-1 infection. A total of
      102 articles were reviewed. The literature shows that a large percentage of HTLV
      1 infected individuals have others neurological symptoms than HAM/TSP. Increased
      understanding of these numerous others clinical manifestations associated to the
      virus than adult T cell leukemia/lymphoma (ATLL) and HAM/TSP has challenged the
      view that HTLV-1 is a low morbidity infection.

PMID- 23152335
TI  - Quality of life of patients with hepatitis C.
AB  - INTRODUCTION: Self-report on the quality of life (QOL) is increasingly studied in
      the evaluation of various diseases, especially in chronic ones. However, there
      are few data in the literature focusing the QOL of patients living with chronic
      hepatitis C. The objective of this study was to evaluate the QOL in patients with
      hepatitis C assessed by the World Health Organization Quality of Life Assessment
      (WHOQOL)-bref scale. METHODS: One hundred and eight hepatitis C patients
      attending the Outpatient Healthcare Medical Specialties in Tubarao, State of
      Santa Catarina, Brazil, were contacted from May 2010 to February 2011. Patients
      answered the WHOQOL-bref scale and a questionnaire about their treatment and risk
      factors to hepatitis C virus (VHC) infection. RESULTS: Although most of patients
      with chronic hepatitis C considered their QoL good or very good (58.1%), 47
      (44.8%) patients were poorly or very poorly satisfied with their health. About
      the WHOQOL answers, the environment domain had the highest score (25.15 + 5.77),
      while the lowest score was the social relationships domain (9.19 + 2.5). There
      was statistically significant association between household income and quality of
      life in all domains (p<0.001) and statistically significant association between
      education and the physical, psychological and social domains of quality of life
      (p<0.05). CONCLUSIONS: Based on the answers given in WHOQOL-bref, patients with
      chronic hepatitis C have a generally poor QOL, especially in social relationship
      domain. Household income and educational level were factors that interfered
      significantly with patients' QOL assessment.

PMID- 23152336
TI  - Occult hepatitis B virus infection in hemodialysis patients in Recife, State of
      Pernambuco, Brazil.
AB  - INTRODUCTION: Persistence of the hepatitis B virus (HBV) genome in individuals
      negative for the HBV surface antigen (HBsAg) reflects occult infection. The aim
      of this study was to identify occult HBV infection among hemodialysis patients at
      5 clinics in Recife, State of Pernambuco, Brazil, between August 2006 and August
      2007. METHODS: Serum samples underwent enzyme-linked immunosorbent assay to
      investigate total antibodies against HBcAg (anti-HBc), HBsAg, and antibodies
      against HBsAg (anti-HBs). Samples that were HBsAg-negative were tested for total
      anti-HBc, and those that were positive for total anti-HBc were tested for anti
      HBs. HBV DNA was investigated with an in-house PCR technique to identify samples
      positive for total anti-HBc. Subsequently, the samples positive for HBV DNA were
      sequenced to identify the genotype and mutations. RESULTS: The study population
      (n = 752) had a mean age of 50 15.1 years and included both sexes. All samples
      analyzed were negative for HBsAg. The seroprevalence of total anti-HBc was 26.7%
      (201/752), while that of anti-HBs was 67.2% (135/201). Total anti-HBc alone was
      detected in 5.7% of the patients. Occult infection was found in 1.5%, comprising
      genotypes A (33.3%, 1/3) and D (66.7%, 2/3). No mutations were found.
      CONCLUSIONS: The study detected occult hepatitis B virus infection in
      hemodialysis patients. Molecular studies on HBV are of fundamental importance
      because they identify patients that had been considered virus-negative but who,
      in reality, host the virus and have the ability to transmit it to other patients
      and staff.

PMID- 23152337
TI  - Surveillance of influenza A H1N1 2009 among school children during 2009 and 2010
      in Sao Paulo, Brazil.
AB  - INTRODUCTION: Influenza A H1N1 2009 is associated with a high morbidity rate
      among children around the world, including Brazil. This survey was conducted on
      samples of symptomatic children (< 12 years) to investigate the influenza virus
      as the etiological agent of respiratory infections in a day care school in a
      health facility during the first and second pandemic wave of H1N1 (2009-2010) in
      Sao Paulo, Brazil. METHODS: Influenza infections were determined by real-time PCR
      in 34% (47/137) of children with a median age of 5 years (8 months - 12 years),
      from June to October 2009 and in 16% (14/85) of those with median age of 6 years
      (1-12 years), from March to November 2010. RESULTS: In general, most positive
      cases (64%) occurred in children aged 5-12 years, this age group was
      significantly the most affected (39.8%, p = 0.001, OR = 8.3, CI 95% 1.9-36.9).
      Wheezing was reported by 31% (19/61) and dyspnea by 23% (14/61) of the studied
      patients. An outbreak of influenza H1N1 with an attack rate of 35.7% among
      children (median age 6 years) was documented in April 2010, before the
      vaccination campaign against the pandemic virus was extended for children up to 5
      years in Brazil. CONCLUSIONS: Therefore, the study reinforces the recommendation
      to immunize school children to reduce the incidence of the disease.

PMID- 23152338
TI  - Occurrence of Triatoma costalimai (Hemiptera: Reduviidae) in different
      environments and climatic seasons: a field study in the Brazilian savanna.
AB  - INTRODUCTION: Trypanosoma cruzi-infected specimens of Triatoma costalimai have
      been detected in domiciliary units of Central Brazil, thereby maintaining the
      potential risk of vectorial transmission of Chagas disease. The aim of this study
      was to determine the occurrence and natural infection of T. costalimai in
      different environments (gallery forest, dry forest and peridomicile) and climatic
      seasons (wet and dry), in the municipality of Mambai, State of Goias, Brazil.
      METHODS: Triatomines were captured in October 2010 and in June 2011, employing
      two different methods (manual capture and mouse-baited adhesive traps). The
      insects were later separated by sex and nymphal stage, counted and examined
      parasitologically by abdominal compression and microscopic analysis of feces.
      RESULTS: Triatoma costalimai was found in three environments and in the two
      seasons studied. Overall, capture success of 900 traps and 60 blocks of rocks
      inspected was 5.8% and 11.7%, respectively. The occurrence of T. costalimai was
      higher among rocks in the peridomicile, where 97% of the 131 specimens were
      captured. The proportion of nymphs (98%) was much higher than that of adults,
      which were only detected in peridomicile. Most (95%) insects were captured during
      the wet season, with predominance of early-stage nymphs. None of the 43 specimens
      examined were infected by trypanosomatids. CONCLUSIONS: The results indicate a
      greater occurrence of T. costalimai in peridomiciliary environments and during
      the wet season in Mambai, Goias, highlighting the synanthropic behavior of this
      triatomine species in one area of the Brazilian savanna and the importance of
      entomological surveillance.

PMID- 23152339
TI  - Multidrug resistance genes, including bla(KPC) and bla(CTX)-M-2, among Klebsiella
      pneumoniae isolated in Recife, Brazil.
AB  - INTRODUCTION: The prevalence of cephalosporins and carbapenem-resistant
      Klebsiella pneumoniae strains is rising in Brazil, with potential serious
      consequences in terms of patients' outcomes and general care. METHODS: This study
      characterized 24 clinical isolates of K. pneumoniae from two hospitals in Recife,
      Brazil, through the antimicrobial susceptibility profile, analyses of beta
      lactamase genes (bla(TEM), bla(SHV),bla(CTX-M), bla(KPC), bla(VIM), bla(IMP), and
      bla(SPM), plasmidial profile and ERIC-PCR (Enterobacterial repetitive intergenic
      consensus-polymerase chain reaction). RESULTS: ERIC-PCR and plasmidial analysis
      grouped the isolates in 17 and 19 patterns, respectively. Six isolates from one
      hospital presented the same pattern by ERIC-PCR, indicating clonal dissemination.
      All isolates presented bla(SHV), 62.5% presented bla(CTX)-M-2, 29% bla(TEM), and
      41.7% bla(KPC). Metallo-beta-lactamase genes bla(VIM), bla(IMP), and bla(SPM) not
      detected. Eleven isolates were identified carrying at least 3 beta-lactamase
      studied genes, and 2 isolates carried bla(SHV), bla(TEM), bla (CTX-M-2) and
      bla(KPC) simultaneously. CONCLUSIONS: The accumulation of resistance genes in
      some strains, observed in this study, imposes limitations in the therapeutic
      options available for the treatment of infections caused by K. pneumoniae in
      Recife, Brazil. These results should alert the Brazilian medical authorities to
      establish rigorous methods for more efficiently control the dissemination of
      antimicrobial resistance genes in the hospital environment.

PMID- 23152340
TI  - Prevalence of enterotoxin-encoding genes and antimicrobial resistance in
      coagulase-negative and coagulase-positive Staphylococcus isolates from black
      pudding.
AB  - INTRODUCTION: Staphylococcal species are pathogens that are responsible for
      outbreaks of foodborne diseases. The aim of this study was to investigate the
      prevalence of enterotoxin-genes and the antimicrobial resistance profile in
      staphylococcus coagulase-negative (CoNS) and coagulasepositive (CoPS) isolates
      from black pudding in southern Brazil. METHODS: Two hundred typical and atypical
      colonies from Baird-Parker agar were inoculated on mannitol salt agar. Eighty-two
      mannitol-positive staphylococci were submitted to conventional biochemical tests
      and antimicrobial susceptibility profiling. The presence of coagulase (coa) and
      enterotoxin (se) genes was investigated by polymerase chain reaction. RESULTS:
      The isolates were divided into 2 groups: 75.6% (62/82) were CoNS and 24.4%
      (20/82) were CoPS. The biochemical tests identified 9 species, of which
      Staphylococcus saprophyticus (37.8%) and Staphylococcus carnosus (15.9%) were the
      most prevalent. Antimicrobial susceptibility tests showed resistance phenotypes
      to antibiotics widely administered in humans, such as gentamicin, tetracycline,
      chloramphenicol, and erythromycin. The coa gene was detected in 19.5% (16/82) of
      the strains and 4 polymorphic DNA fragments were observed. Five CoNS isolates
      carrying the coa gene were submitted for 16S rRNA sequencing and 3 showed
      similarity with CoNS. Forty strains were positive for at least 1 enterotoxin
      encoding gene, the genes most frequently detected were sea (28.6%) and seb
      (27.5%). CONCLUSIONS: The presence of antimicrobial resistant and enterotoxin
      encoding genes in staphylococci isolates from black pudding indicated that this
      fermented food may represent a potential health risk, since staphylococci present
      in food could cause foodborne diseases or be a possible route for the transfer of
      antimicrobial resistance to humans.

PMID- 23152341
TI  - Paracoccidioidomycosis case series with and without central nervous system
      involvement.
AB  - INTRODUCTION: Paracoccidioidomycosis (PCM) is the most important systemic mycosis
      in South America. Central nervous system involvement is potentially fatal and can
      occur in 12.5% of cases. This paper aims to contribute to the literature
      describing eight cases of neuroparacoccidioidomycosis (NPMC) and compare their
      characteristics with patients without neurological involvement, to identify
      unique characteristics of NPCM. METHODS: A cohort of 213 PCM cases was evaluated
      at the Infectious Diseases Clinic of the University Hospital, Federal University
      of Minas Gerais, Brazil, from October 1976 to August 2008. Epidemiological,
      clinical, laboratory, therapeutic and follow-up data were registered. RESULTS:
      Eight patients presented NPCM. The observed NPCM prevalence was 3.8%. One patient
      presented the subacute form of PCM and the other seven presented the chronic form
      of the disease. The parenchymatous form of NPCM occurred in all patients. 60% of
      the patients who proceeded from the north/ northeast region of Minas Gerais State
      developed NPCM. The neurological involvement of a mother and her son was
      observed. NPCM patients exhibited demographical and clinical profiles similar to
      what is described in the literature. When NPCM cases were compared to PCM
      patients, there were differences in relation to origin and positive PCM family
      history. CONCLUSIONS: The results corroborate the clinical view that the
      neurological findings are extremely important in the evaluation of PCM patients.
      Despite the limitations of this study, the differences in relation to patient's
      origins and family history point to the need of further studies to determine the
      susceptibility factors involved in the neurological compromise.

PMID- 23152342
TI  - Multiple causes of death related to Chagas' disease in Brazil, 1999 to 2007.
AB  - INTRODUCTION: Chagas' disease is a major public health problem in Brazil and
      needs extensive and reliable information to support consistent prevention and
      control actions. This study describes the most common causes of death associated
      with deaths related to Chagas' disease (underlying or associated cause of death).
      METHODS: Mortality data were obtained from the Mortality Information System of
      the Ministry of Health (approximately 9 million deaths). We analyzed all deaths
      that occurred in Brazil between 1999 and 2007, where Chagas' disease was
      mentioned on the death certificate as underlying or associated cause (multiple
      causes of death). RESULTS: There was a total of 53,930 deaths related to Chagas'
      disease, 44,543 (82.6%) as underlying cause and 9,387 (17.4%) as associated
      cause. The main diseases and conditions associated with death by Chagas' disease
      as underlying cause included direct complications of cardiac involvement, such as
      conduction disorders/arrhythmias (41.4%) and heart failure (37.7%).
      Cerebrovascular disease (13.2%), ischemic heart disease (13.2%) and hypertensive
      diseases (9.3%) were the main underlying causes of deaths in which Chagas'
      disease was identified as an associated cause. CONCLUSIONS: Cardiovascular
      diseases were often associated with deaths related to Chagas' disease.
      Information from multiple causes of death recorded on death certificates allows
      reconstruction of the natural history of Chagas' disease and suggests preventive
      and therapeutic potential measures more adequate and specifics.

PMID- 23152343
TI  - The effect of age on the frequency of adverse reactions caused by antimony in the
      treatment of American tegumentary leishmaniasis in Governador Valadares, State of
      Minas Gerais, Brazil.
AB  - INTRODUCTION: Governador Valadares is an endemic area of American tegumentary
      leishmaniasis (ATL). The detection rate was 15.36 per 100,000 habitants from 2001
      to 2006 (Miranda, 2008). This study aimed to analyze the effects of age on the
      frequency of adverse reactions caused by antimony in the treatment of ATL in the
      City of Governador Valadares, State of Minas Gerais, Brazil, during 2009.
      METHODS: Data were collected from the forms of the Information System for
      Notifiable Diseases, and from charts, questionnaires, and home visits to
      patients. RESULTS: The study included 40 patients, 26 (65%) of whom were males.
      Individuals over the age of 50 had a 66% higher rate of adverse effects than
      subjects who were 50 years old or less (CI 95%, 1.14-2.41). The average age of
      individuals who reported some type of adverse effect was 44.11 years (SD =
      20.14), while the average age of the group that did not report any adverse effect
      was of 25.46 years (SD = 18.37; p < 0.01). Clinical healing was 67.5%, and 10% of
      patients discontinued the treatment. CONCLUSIONS: In the treatment of ATL, the
      age of patients should be considered, because most adverse reactions occur in
      individuals over 50 years of age. For this reason, the drug should be used with
      restriction in these cases.

PMID- 23152344
TI  - Profile and geographic distribution of reported cases of visceral leishmaniasis
      in Campo Grande, State of Mato Grosso do Sul, Brazil, from 2002 to 2009.
AB  - INTRODUCTION: This study sought to describe the profile and geographic
      distribution of reported cases of visceral leishmaniasis (VL) in the City of
      Campo Grande, State of Mato Grosso do Sul (MS), Brazil, from 2002 to 2009.
      METHODS: Human data were collected from the Brazilian National Information System
      for Notifiable Diseases. Canine cases and entomological data were obtained from
      the Information Service for Canine Visceral Leishmaniasis Control/Campo Grande,
      MS. RESULTS: A total of 951 records from 2002 to 2009 were investigated. The
      number of reported cases of VL in males was significantly higher (p < 0.0001)
      than that in females. The higher frequency observed among males was associated
      with age (p < 0.0001), which increased in individuals aged 40 years and older.
      The overall fatality rate was 7.4%. Entomological surveys conducted in 2006,
      2007, and 2009 showed the insect vector Lutzomyia longipalpis to be present in
      all urban regions of the county. CONCLUSIONS: VL cases in humans and dogs, as
      well as in vectors, occurs in all urban regions of Campo Grande. Despite not
      observing tendencies of increase or reduction in the incidence of the disease due
      to aging, the major incidence in men is higher in those aged 40 years or above.

PMID- 23152345
TI  - Spatio-temporal patterns of tuberculosis incidence in Ribeirao Preto, State of
      Sao Paulo, southeast Brazil, and their relationship with social vulnerability: a
      Bayesian analysis.
AB  - INTRODUCTION: The purpose of this ecological study was to evaluate the urban
      spatial and temporal distribution of tuberculosis (TB) in Ribeirao Preto, State
      of Sao Paulo, southeast Brazil, between 2006 and 2009 and to evaluate its
      relationship with factors of social vulnerability such as income and education
      level. METHODS: We evaluated data from TBWeb, an electronic notification system
      for TB cases. Measures of social vulnerability were obtained from the SEADE
      Foundation, and information about the number of inhabitants, education and income
      of the households were obtained from Brazilian Institute of Geography and
      Statistics. Statistical analyses were conducted by a Bayesian regression model
      assuming a Poisson distribution for the observed new cases of TB in each area. A
      conditional autoregressive structure was used for the spatial covariance
      structure. RESULTS: The Bayesian model confirmed the spatial heterogeneity of TB
      distribution in Ribeirao Preto, identifying areas with elevated risk and the
      effects of social vulnerability on the disease. We demonstrated that the rate of
      TB was correlated with the measures of income, education and social
      vulnerability. However, we observed areas with low vulnerability and high
      education and income, but with high estimated TB rates. CONCLUSIONS: The study
      identified areas with different risks for TB, given that the public health system
      deals with the characteristics of each region individually and prioritizes those
      that present a higher propensity to risk of TB. Complex relationships may exist
      between TB incidence and a wide range of environmental and intrinsic factors,
      which need to be studied in future research.

PMID- 23152346
TI  - Concordance between expected and observed bacilloscopy results of clinical forms
      of leprosy: a 6-year retrospective study in Recife, State of Pernambuco, Brazil.
AB  - INTRODUCTION: Operational classification of leprosy based on the number of skin
      lesions was conceived to screen patients presenting severe forms of the disease
      to enable their reception of a more intense multidrug regimen without having to
      undergo lymph smear testing. We evaluated the concordance between operational
      classification and bacilloscopy to define multibacillary and paucibacillary
      leprosy. METHODS: We selected 1,213 records of individuals with leprosy, who were
      untreated (new cases) and admitted to a dermatology clinic in Recife, Brazil,
      from 2000 to 2005, and who underwent bacteriological examination at diagnosis for
      ratification of the operational classification. RESULTS: Compared to
      bacilloscopy, operational classification demonstrated 88.6% sensitivity, 76.9%
      specificity, a positive predictive value of 61.8%, and a negative predictive
      value of 94.1%, with 80% accuracy and a moderate kappa index. Among the
      bacilloscopy-negative cases, 23% had more than 5 skin lesions. Additionally, 11%
      of the bacilloscopy-positive cases had up to 5 lesions, which would have led to
      multibacillary cases being treated as paucibacillary leprosy if the operational
      classification had not been confirmed by bacilloscopy. CONCLUSIONS: Operational
      classification has limitations that are more obvious in borderline cases,
      suggesting that in these cases, lymph smear testing is advisable to enable the
      selection of true multibacillary cases for more intense treatment, thereby
      contributing to minimization of resistant strain selection and possible relapse.

PMID- 23152347
TI  - Glutathione levels in and total antioxidant capacity of Candida sp. cells exposed
      to oxidative stress caused by hydrogen peroxide.
AB  - INTRODUCTION: The capacity to overcome the oxidative stress imposed by phagocytes
      seems to be critical for Candida species to cause invasive candidiasis. METHODS:
      To better characterize the oxidative stress response (OSR) of 8 clinically
      relevant Candida sp., glutathione, a vital component of the intracellular redox
      balance, was measured using the 5,5'-dithiobis-(2-nitrobenzoic acid (DTNB)
      glutathione disulfide (GSSG) reductase reconversion method; the total antioxidant
      capacity (TAC) was measured using a modified method based on the decolorization
      of the 2,2'-azinobis-(3-ethylbenzothiazoline-6-sulfonic) acid radical cation
      (ABTS*+). Both methods were used with cellular Candida sp. extracts treated or
      not with hydrogen peroxide (0.5 mM). RESULTS: Oxidative stress induced by
      hydrogen peroxide clearly reduced intracellular glutathione levels. This
      depletion was stronger in Candida albicans and the levels of glutathione in
      untreated cells were also higher in this species. The TAC demonstrated intra
      specific variation. CONCLUSIONS: Glutathione levels did not correlate with the
      measured TAC values, despite this being the most important non-enzymatic
      intracellular antioxidant molecule. The results indicate that the isolated
      measurement of TAC does not give a clear picture of the ability of a given
      Candida sp. to respond to oxidative stress.

PMID- 23152348
TI  - Schistosoma mansoni granuloma in late evolutive phase, in a case of tumoral form
      in man.
AB  - INTRODUCTION: Authors describe human schistosomal granuloma in late chronic
      phase, from the morphological and evolutionary viewpoints. METHODS: The study was
      based on a histological analysis of two fragments obtained from a surgical biopsy
      of peritoneum and large intestine of a 42-year-old patient, with a pseudotumoral
      form mimicking a peritoneal carcinomatosis associated to the schistosomiasis
      hepatointestinal form. RESULTS: Two hundred and three granulomas were identified
      in the pseudotumor and 27 in the intestinal biopsy, with similar morphological
      features, most in the late chronic phase, in fibrotic healing. A new structural
      classification was suggested for granulomas: zone 1 (internal), 2 (intermediate)
      and 3 (external). CONCLUSIONS: Regarding granuloma as a whole, we may conclude
      that fibrosis is likely to be controlled by different and independent mechanisms
      in the three zones of the granuloma. Lamellar fibrosis in zone 3 seems to be
      controlled by matrix mesenchymal cells (fibroblasts and myoepithelial cells) and
      by inflammatory exudate cells (lymphocytes, plasmocytes, neutrophils,
      eosinophils). Annular fibrosis in zone 2, comprising a dense fibrous connective
      tissue, with few cells in the advanced phase, would be controlled by epithelioid
      cells involving zone 1 in recent granulomas. In zone 1, replacing periovular
      necrosis, an initialy loose and tracery connective neoformation, housing stellate
      cells or with fusiform nuclei, a dense paucicellular nodular connective tissue
      emerges, probably induced by fibroblasts. In several granulomas, one of the zones
      is missing and granuloma is represented by two of them: Z3 and Z2, Z3 and Z1 or
      Z2 and Z1 and, ultimately, by a scar.

PMID- 23152349
TI  - Spatial distribution of schistosomiasis and geohelminthiasis cases in the rural
      areas of Pernambuco, Brazil.
AB  - INTRODUCTION: The prevalence and intensity of geohelminth infections and
      schistosomiasis remain high in the rural areas of Zona da Mata, Pernambuco (ZMP),
      Brazil, where these parasites still represent a significant public health
      problem. The present study aimed to spatially assess the occurrences of
      schistosomiasis and geohelminthiasis in the ZMP. METHODS: The ZMP has a
      population of 1,132,544 inhabitants, formed by 43 municipalities. An ecological
      study was conducted, using secondary data relating to positive human cases and
      parasite loads of schistosomiasis and positive human cases of geohelminthiasis
      that were worked up in Excel 2007. We used the coordinates of the municipal
      headquarters to represent the cities which served as the unit of analysis of this
      study. The Kernel estimator was used to spatially analyze the data and identify
      distribution patterns and case densities, with analysis done in ArcGIS software.
      RESULTS: Spatial analysis from the Kernel intensity estimator made it possible to
      construct density maps showing that the northern ZMP was the region with the
      greatest number of children infected with parasites and the populations most
      intensely infected by Schistosoma mansoni. In relation to geohelminths, there was
      higher spatial distribution of cases of Ascaris lumbricoides and Trichuris
      trichiura in the southern ZMP, and greater occurrence of hookworms in the
      northern/central ZMP. CONCLUSIONS: Despite several surveys and studies showing
      occurrences of schistosomiasis and geohelminthiasis in the ZMP, no preventive
      measures that are known to have been effective in decreasing these health hazards
      have yet been implemented in the endemic area.

PMID- 23152350
TI  - Hepatitis B revaccination for healthcare workers who are anti-HBs-negative after
      receiving a primary vaccination series.
AB  - INTRODUCTION: This study aimed to evaluate the response to hepatitis B (HB)
      revaccination of healthcare workers (HCW) who are negative for antibodies to HB
      surface antigen (anti-HBs) after a complete vaccination series. METHODS: HCW
      whose anti-HBs test was performed > 90 days after a HB vaccination course were
      given a 4th dose. A post-vaccination test was done within 30 to 90 days. RESULTS:
      One hundred and seventy HCW were enrolled: 126 (74.1%) were anti-HBs-positive
      after the 4th dose. CONCLUSIONS: Rechecking anti-HBs after the 4th HB vaccine
      dose is a practical approach in case of post-vaccination tests performed >90 days
      after the full vaccination course.

PMID- 23152351
TI  - The first record of Lutzomyia longipalpis (Lutz & Neiva, 1912) (Diptera:
      Psychodidae: Phlebotominae) in the State of Parana, Brazil.
AB  - INTRODUCTION: We report the first find of Lutzomyia longipalpis in the State of
      Parana, Brazil. METHODS: The specimens were captured in the urban area of the
      municipality of Foz do Iguacu, with Falcao light traps, in domiciliary and
      peridomiciliary areas of 61 properties, on two consecutive nights from 18:00 to
      06:00hs in March 2012. RESULTS: We captured 40 specimens of Lu. longipalpis and
      54 specimens of other sandfly species. CONCLUSIONS: This find expands knowledge
      of the geographical distribution of this sandfly in Brazil.

PMID- 23152352
TI  - Enterobius vermicularis infection is well controlled among preschool children in
      nurseries of Taipei City, Taiwan.
AB  - INTRODUCTION: Whether Enterobius vermicularis (pinworm) infections among
      preschool children in Taipei City had truly declined was investigated. METHODS: A
      total of 6,661 preschool children from 28 nurseries were randomly selected from 4
      major geographic districts in Taipei City to examine the status of pinworm
      infection by using adhesive thin cellophane tape swab method. RESULTS: The
      overall prevalence of pinworm infection was 0.5% (30/6,661). Boys (0.6%;
      21/3,524) had higher prevalence than girls (0.3%; 9/3,137) (p=0.06). Southern
      district (0.6%; 10/1,789) showed insignificantly higher prevalence than Western
      district (0.2%; 1/606) (p=0.22). CONCLUSIONS: Pinworm screening program remains
      necessary for some parts of Taipei City.

PMID- 23152353
TI  - Bilateral paracoccidioidomycotic iliopsoas abscess associated with ileo-colonic
      lesion.
AB  - This case report shows the clinical development of a patient with systemic
      paracoccidioidomycosis presenting with lymphatic-intestinalmanifestation. The
      patient initially had a substantial clinical improvement but had a recrudescence
      after six months of sulfamethoxazoletrimethoprim oral treatment, with the
      emergence of feverish syndrome, lumbar pain, and intermittent claudication,
      characterizing a bilateral iliopsoas muscle abscess, necessitating
      clinicosurgical therapeutics.

PMID- 23152354
TI  - Fatal disseminated strongyloidiasis after kidney transplantation.
AB  - Disseminated strongyloidiasis (DS) is a rare and severe parasitic disease that is
      difficult to recognize and affects immunocompromised individuals. We report the
      case of a kidney transplant recipient who presented with DS despite prophylaxis
      with albendazole. We have discussed the need for better prophylactic strategies
      and for a higher degree of suspicion in order to diagnose DS.

PMID- 23152355
TI  - Secondary bronchiolitis obliterans organizing pneumonia during treatment of
      chronic hepatitis C: role of pegylated interferon alfa-2a.
AB  - The treatment of chronic hepatitis C has frequent side effects such as cytopenias
      and neuropsychiatric symptoms. However, pulmonary toxicity associated with
      interferon is rarely described. This paper describes the clinical case of a 67
      year-old female patient with chronic hepatitis C who presented an acute onset of
      dry cough, dyspnoea, and fever 36 weeks after the use of pegylated interferon
      alfa-2a and ribavirin. The lung biopsy confirmed the diagnosis of a bronchiolitis
      obliterans organizing pneumonia (BOOP). Corticotherapy was initiated, with
      clinical and radiological improvement. This paper aims to advise physicians to
      this occasional, though severe, adverse event related to hepatitis C virus (HCV)
      treatment.

PMID- 23152356
TI  - Coinfection dengue and melioidosis infection.

PMID- 23152357
TI  - Chest helical computed tomography scan shows pulmonary micronodules and
      condensation in acute schistosomiasis mansoni.

PMID- 23152358
TI  - Internet-delivered cognitive behavioural therapy for depression: a feasibility
      open trial for older adults.
AB  - BACKGROUND: Depression is an important health issue amongst older adults.
      Internet-delivered cognitive behaviour therapy (iCBT) may help to reduce barriers
      and improve access to treatment, but few studies have examined its use with older
      adults. The present study evaluated the efficacy, acceptability and feasibility
      of a brief iCBT program, the Managing Your Mood Program, to treat depression
      amongst adults aged 60 years and older. METHOD: Using an open trial design, 20
      participants with elevated symptoms of depression (Patient Health Questionnaire 9
      item (PHQ-9) total scores >= 10) received access to five educational lessons and
      homework summaries, additional resources, a moderated discussion forum and weekly
      telephone or email contact from a clinical psychologist. Eighty percent of the
      sample met diagnostic criteria for a major depressive episode at pre-treatment.
      RESULTS: Completion rates and response rates were high, with 16/20 participants
      completing the five lessons within the 8 weeks, and post-treatment and 3-month
      follow-up data being collected from 17/20 participants. Participants improved
      significantly on the PHQ-9 and Geriatric Depression Scale (GDS), with large
      within-group effect sizes (Cohen's d) at follow-up of 1.41 and 2.04,
      respectively. The clinician spent a mean time of 73.75 minutes (SD = 36.10
      minutes) contacting participants within the trial and the program was rated as
      highly acceptable by participants. CONCLUSIONS: The results are encouraging and
      support the potential value of iCBT in the treatment of depressive symptoms
      amongst older adults.

PMID- 23152359
TI  - Peer workers' role in smoking-cessation groups for people with mental illness.
AB  - OBJECTIVES: The objective of this article is to evaluate the impact of peer
      workers' involvement as co-leaders in smoking-cessation programmes provided
      within mental health services. METHOD: Group smoking-cessation programmes were
      provided for people living with mental illness. Peer workers were involved in the
      development and delivery of these programmes. Group participants and mental
      health workers were asked to respond to a questionnaire about their experience of
      the peer workers. The questionnaire included both Likert scales and qualitative
      responses. RESULTS: Thirty-three mental health workers and 108 group participants
      completed the questionnaire. The majority of participants believed that the peer
      workers increased their confidence, helped them to learn about smoking cessation
      and promoted well-being. Mental health workers were also positive about the role
      of peer workers in the groups. CONCLUSIONS: This study supports the role of peer
      workers providing support and guidance within smoking-cessation programmes for
      people with mental illness. The results suggest that peer workers make a
      substantial contribution and that greater peer worker involvement in such
      programmes is likely to improve their acceptability and efficacy.

PMID- 23152361
TI  - Irsogladine maleate reduces the incidence of fluorouracil-based chemotherapy
      induced oral mucositis.
AB  - BACKGROUND: Oral mucositis is one of the most common side-effects of 5
      fluorouracil (5-FU)-based chemotherapy. The objective of this study was to
      evaluate the effects of irsogladine maleate (IM) on fluorouracil-induced oral
      mucositis through a double-blind, placebo controlled trial. PATIENTS AND METHODS:
      Patients (N = 66) were randomly assigned to receive either placebo or IM (4
      mg/day for 14 consecutive days). The incidence and maximum severity of
      fluorouracil-induced oral mucositis and safety of the irsogladine dosing regimen
      were evaluated. RESULTS: A cohort of 33 patients received placebo and 33 patients
      received IM. The incidence of oral mucositis was significantly lower for IM than
      for placebo (27% versus 73%; P < 0.001 by chi-square test). Specific adverse
      events considered related to IM were not found. CONCLUSION: IM significantly
      reduced the incidence and maximum severity of oral mucositis in patients treated
      with 5-FU-chemotherapy.

PMID- 23152362
TI  - Effect of abiraterone acetate on fatigue in patients with metastatic castration
      resistant prostate cancer after docetaxel chemotherapy.
AB  - BACKGROUND: Fatigue is a common, debilitating side-effect of prostate cancer and
      its treatment. Patient-reported fatigue was evaluated as part of COU-AA-301, a
      randomized, placebo-controlled, phase III trial of abiraterone acetate and
      prednisone versus placebo and prednisone in metastatic castration-resistant
      prostate cancer (mCRPC) patients after docetaxel chemotherapy. This is the first
      phase III study in advanced prostate cancer to evaluate fatigue outcomes using a
      validated fatigue-specific instrument. PATIENTS AND METHODS: The Brief Fatigue
      Inventory (BFI) questionnaire was used to measure patient-reported fatigue
      intensity and fatigue interference with activities of daily life. All analyses
      were conducted using prespecified responder definitions of clinically meaningful
      changes. RESULTS: A total of 797 patients were randomized to abiraterone acetate
      and prednisone, and 398 were randomized to placebo and prednisone. Compared with
      prednisone alone, in patients with clinically significant fatigue at baseline,
      abiraterone acetate and prednisone significantly increased the proportion of
      patients reporting improvement in fatigue intensity (58.1% versus 40.3%, P =
      0.0001), improved fatigue interference (55.0% versus 38.0%, P = 0.0075), and
      accelerated improvement in fatigue intensity (median 59 days versus 194 days, P =
      0.0155). CONCLUSIONS: In patients with mCRPC progressing after docetaxel
      chemotherapy, abiraterone acetate and prednisone yielded clinically meaningful
      improvements in patient-reported fatigue compared with prednisone alone.

PMID- 23152360
TI  - Maintaining success, reducing treatment burden, focusing on survivorship:
      highlights from the third European consensus conference on diagnosis and
      treatment of germ-cell cancer.
AB  - In November 2011, the Third European Consensus Conference on Diagnosis and
      Treatment of Germ-Cell Cancer (GCC) was held in Berlin, Germany. This third
      conference followed similar meetings in 2003 (Essen, Germany) and 2006
      (Amsterdam, The Netherlands) [Schmoll H-J, Souchon R, Krege S et al. European
      consensus on diagnosis and treatment of germ-cell cancer: a report of the
      European Germ-Cell Cancer Consensus Group (EGCCCG). Ann Oncol 2004; 15: 1377
      1399; Krege S, Beyer J, Souchon R et al. European consensus conference on
      diagnosis and treatment of germ-cell cancer: a report of the second meeting of
      the European Germ-Cell Cancer Consensus group (EGCCCG): part I. Eur Urol 2008;
      53: 478-496; Krege S, Beyer J, Souchon R et al. European consensus conference on
      diagnosis and treatment of germ-cell cancer: a report of the second meeting of
      the European Germ-Cell Cancer Consensus group (EGCCCG): part II. Eur Urol 2008;
      53: 497-513]. A panel of 56 of 60 invited GCC experts from all across Europe
      discussed all aspects on diagnosis and treatment of GCC, with a particular focus
      on acute and late toxic effects as well as on survivorship issues. The panel
      consisted of oncologists, urologic surgeons, radiooncologists, pathologists and
      basic scientists, who are all actively involved in care of GCC patients.
      Panelists were chosen based on the publication activity in recent years. Before
      the meeting, panelists were asked to review the literature published since 2006
      in 20 major areas concerning all aspects of diagnosis, treatment and follow-up of
      GCC patients, and to prepare an updated version of the previous recommendations
      to be discussed at the conference. In addition, ~50 E-vote questions were drafted
      and presented at the conference to address the most controversial areas for a
      poll of expert opinions. Here, we present the main recommendations and
      controversies of this meeting. The votes of the panelists are added as online
      supplements.

PMID- 23152363
TI  - Dehydroepiandrosterone sulfate levels and risk of atrial fibrillation: the
      Rotterdam Study.
AB  - BACKGROUND: High plasma dehydroepiandrosterone sulfate (DHEAS) levels have been
      associated with a reduced risk of cardiovascular disease and atherosclerosis. To
      our knowledge, no previous follow-up study has investigated the association
      between DHEAS and the development of atrial fibrillation. Our objective was to
      investigate the association between DHEAS levels and incident atrial
      fibrillation. METHODS AND RESULTS: The study was based on a random sample within
      the prospective population-based Rotterdam Study. The study population comprised
      1180 participants without atrial fibrillation at baseline for whom baseline
      levels of DHEAS were measured in plasma. Atrial fibrillation was ascertained from
      centre visit electrocardiogram (ECG) assessments as well as medical records.
      During a mean follow-up period of 12.3 years, 129 participants developed atrial
      fibrillation. DHEAS levels were inversely associated with the risk of atrial
      fibrillation (hazard ratio (HR) per standard deviation (SD): 0.74, 95% confidence
      interval (CI): 0.58-0.94). Subjects in the highest DHEAS quartile had an almost
      three times lower risk of atrial fibrillation during follow-up, compared to those
      in the lowest DHEAS quartile (HR: 0.34, 95% CI: 0.18-0.64) adjusted for age, sex
      and cardiovascular risk factors. CONCLUSION: DHEAS can be regarded as an
      important indicator of future atrial fibrillation in both men and women,
      independent of known cardiovascular risk factors.

PMID- 23152364
TI  - Biodegradable versus durable polymer drug eluting stents in coronary artery
      disease: insights from a meta-analysis of 5,834 patients.
AB  - BACKGROUND: Biodegradable polymer drug eluting stents (BP-DES) have been
      developed to overcome the limitations of first generation durable polymer DES (DP
      DES) but the clinical results of different BP-DES are not consistent. We
      performed a meta-analysis to compare the outcomes of BP-DES and DP-DES in the
      treatment of coronary artery disease (CAD). METHODS AND RESULTS: Online databases
      including MEDLINE were searched for studies comparing BP-DES and DP-DES for
      obstructive CAD that reported rates for overall mortality, myocardial infarction
      (MI), late stent thrombosis (LST), target lesion revascularization (TLR) and late
      lumen loss (LLL) with a follow-up of >= 6 months. Ten studies (5834 patients)
      with a 1-year median follow-up were included in the meta-analysis. When comparing
      patients treated with DP-DES and BP-DES those treated with BP-DES had lower LLL
      (in-stent: weighted mean difference (WMD) -0.10 mm, 95% CI = -0.17 to -0.03 mm, p
      = 0.004; in-segment: WMD -0.06 mm, 95% CI = -0.10 to -0.01 mm, p = 0.01) with
      lower TLR rates (OR 0.67, 95% CI = 0.47 to 0.98, p = 0.04). However, BP-DES did
      not improve mortality (OR 0.97, 95% CI = 0.73 to 1.29, p = 0.83), MI (OR 1.13,
      95% CI = 0.87 to 1.46, p = 0.36) or LST rates (OR 0.64, 95% CI = 0.36 to 1.16, p
      = 0.14). A pre-specified subgroup analysis of Biolimus BP-DES confirmed
      significant LLL reduction without differences in other clinical endpoints. Meta
      regression analysis demonstrated a strong significant inverse correlation between
      LLL and reference coronary diameter (p < 0.001). CONCLUSIONS: Our present meta
      analysis showed that BP-DES when compared with DP-DES significantly reduced LLL
      and TVR but without clear benefits on mortality, MI and LST rates.
      (Clinicaltrials.gov identifier: NCT01466634).

PMID- 23152366
TI  - The genetic diversity of Citrus dwarfing viroid populations is mainly dependent
      on the infected host species.
AB  - As with viruses, viroids infect their hosts as polymorphic populations of
      variants. Identifying possible sources of genetic variability is significant in
      the case of the species Citrus dwarfing viroid (CDVd) which has been proposed as
      a dwarfing agent for high-density citrus plantings. Here, a natural CDVd isolate
      (CMC) was used as an inoculum source for long-term (25 years) and short-term (1
      year) bioassays in different citrus host species. Characterization of progenies
      indicated that the genetic stability of CDVd populations was high in certain
      hosts (trifoliate orange, Troyer citrange, Etrog citron, Navelina sweet orange),
      which preserve viroid populations similar to the original CMC isolate even after
      25 years. By contrast, CDVd variant populations in Interdonato lemon and Volkamer
      lemon were completely different to those in the inoculated sources, highlighting
      how influential the host is on the genetic variability of CDVd populations.
      Implications for risk assessment of CDVd as a dwarfing agent are discussed. The
      GenBank/EMBL/DDBJ accession numbers for the complete sequences of the Citrus
      dwarfing viroid variants are JF970266.1 forH2-2, JF970267.1 for H2-7, EU938647.1
      for H6-2, EU938651.1 forH6-10, JF970268.1 for H10-7, EU938652.1 for H14-13,
      EU938653.1for H14-14, JF970269.1 for H14-16, EU938648.1 for H15-9,EU938649.1 for
      H16-2, JF970265.1 for H16-9, EU938654.1 forH16-13, EU938650.1 for H20-3,
      JF970270.1 for H20-7, EU938641.1for PR-1, EU938642.1 for PR-3, EU938643.1 for PR
      7, EU938644.1for CR-1, EU938639.1 for VR-4, JF12070.1 for VR-15, JF812069.1LS-4,
      EU938640.1 for LS-10 and JF970264.1 for LS-11.

PMID- 23152365
TI  - Effects of Tat proteins and Tat mutants of different human immunodeficiency virus
      type 1 clades on glial JC virus early and late gene transcription.
AB  - Polyomavirus JC (JCV) is the aetiological agent of progressive multifocal
      leukoencephalopathy (PML), a frequently fatal infection of the brain afflicting
      nearly 4% of AIDS patients in the USA. Human immunodeficiency virus type 1 (HIV
      1) Tat, acting together with cellular proteins at the JCV non-coding control
      region (NCCR), can stimulate JCV DNA transcription and replication. Tat in the
      brain is secreted by HIV-1-infected cells and incorporated by oligodendroglia,
      cells capable of infection by JCV. Thus far the effects of Tat on JCV have been
      studied primarily with protein encoded by the HIV-1 B clade most common in North
      America. Here, we determine the abilities of Tat from different HIV-1 clades to
      alter JCV early and late gene transcription and DNA replication initiated at the
      JCV origin. Tat from all clades tested stimulates both JCV early and late gene
      promoters, with clade B Tat being significantly most effective. Tat proteins from
      the HIV-1 clades display parallel patterns of differences in their effects on HIV
      1 and JCV transcription, suggesting that Tat effects in both cases are mediated
      by the same cellular proteins. Clade B Tat is most effective at directing Smad
      mediators of tumour growth factor beta and cellular partner Puralpha to the NCCR.
      Tat proteins from all non-B clades inhibit initiation of JCV DNA replication. The
      effectiveness of HIV-1 clade B Tat at promoting JCV transcriptional and
      replicative processes highlights a need for further investigation to determine
      which molecular aspects of Tat from distinct HIV-1 substrains can contribute to
      the course of PML development in neuroAIDS.

PMID- 23152367
TI  - Phylogenetic analysis of bluetongue virus serotype 4 field isolates from
      Argentina.
AB  - Bluetongue is an insect-transmitted viral disease of ruminant species, which
      represents a major barrier to the international trade of animals and their
      products. Bluetongue virus (BTV) has a genome composed of ten linear segments of
      dsRNA, which code for at least ten different viral proteins. In South America,
      serological evidence for the presence of BTV has been found in Peru, Argentina,
      Brazil, Ecuador and Chile. Brazil and Argentina are the only South American
      countries where BTV has been isolated. In Brazil, only one BTV isolate, serotype
      12, has been reported, whereas in Argentina five BTV serotype 4 isolates have
      been obtained from cattle without clinical signs. Three of these five isolates
      were isolated during 1999-2001, whereas two of them were obtained as part of the
      present work. This study describes sequence comparisons and phylogenetic analyses
      of segment (Seg)-2, Seg-3, Seg-6, Seg-7 and Seg-10 of the first Argentinian field
      isolates of BTV. The analysis of Seg-2 and Seg-6 resulted in a single cluster of
      Argentinian sequences into the serotype 4 clade. In addition, the Argentinian
      sequences grouped within the nucleotype A clade, along with reference strains.
      The analysis of Seg-3, Seg-7 and Seg-10 showed that the Argentinian isolates
      grouped into the western topotype, indicating that the circulating virus had an
      African/European origin. Phylogenetic analysis revealed that the Argentinian
      sequences present a South American genetic identity, suggesting an independent
      lineage evolution.

PMID- 23152368
TI  - Differentially regulated gene expression associated with hepatitis C virus
      clearance.
AB  - Human chronic hepatitis C virus (HCV) infections pose a significant public health
      threat, necessitating the development of novel treatments and vaccines. HCV
      infections range from spontaneous resolution to end-stage liver disease.
      Approximately 10-30% of HCV infections undergo spontaneous resolution independent
      of treatment by yet-to-be-defined mechanisms. These individuals test positive for
      anti-HCV antibodies in the absence of detectable viral serum RNA. To identify
      genes associated with HCV clearance, this study compared gene expression profiles
      between current drug users chronically infected with HCV and drug users who
      cleared their HCV infection. This analysis identified 91 differentially regulated
      (up- or downregulated by twofold or more) genes potentially associated with HCV
      clearance. The majority of genes identified were associated with immune function,
      with the remaining genes categorized either as cancer related or 'other'.
      Identification of factors and pathways that may influence virus clearance will be
      essential to the development of novel treatment strategies.

PMID- 23152369
TI  - Human T-cells directed to seasonal influenza A virus cross-react with 2009
      pandemic influenza A (H1N1) and swine-origin triple-reassortant H3N2 influenza
      viruses.
AB  - Virus-specific CD8(+) T-cells contribute to protective immunity against influenza
      A virus (IAV) infections. As the majority of these cells are directed to
      conserved viral proteins, they may afford protection against IAVs of various
      subtypes. The present study assessed the cross-reactivity of human CD8(+) T
      lymphocytes, induced by infection with seasonal A (H1N1) or A (H3N2) influenza
      virus, with 2009 pandemic influenza A (H1N1) virus [A(H1N1)pdm09] and swine
      origin triple-reassortant A (H3N2) [A(H3N2)v] viruses that are currently causing
      an increasing number of human cases in the USA. It was demonstrated that CD8(+) T
      cells induced after seasonal IAV infections exerted lytic activity and produced
      gamma interferon upon in vitro restimulation with A(H1N1)pdm09 and A(H3N2)v
      influenza A viruses. Furthermore, CD8(+) T-cells directed to A(H1N1)pdm09 virus
      displayed a high degree of cross-reactivity with A(H3N2)v viruses. It was
      concluded that cross-reacting T-cells had the potential to afford protective
      immunity against A(H1N1)pdm09 viruses during the pandemic and offer some degree
      of protection against infection with A(H3N2)v viruses.

PMID- 23152370
TI  - Full-length genome sequences of five hepatitis C virus isolates representing
      subtypes 3g, 3h, 3i and 3k, and a unique genotype 3 variant.
AB  - We characterized the full-length genomes of five distinct hepatitis C virus (HCV)
      3 isolates. These represent the first complete genomes for subtypes 3g and 3h,
      the second such genomes for 3k and 3i, and of one novel variant presently not
      assigned to a subtype. Each genome was determined from 18-25 overlapping
      fragments. They had lengths of 9579-9660 nt and each contained a single ORF
      encoding 3020-3025 aa. They were isolated from five patients residing in Canada;
      four were of Asian origin and one was of Somali origin. Phylogenetic analysis
      using 64 partial NS5B sequences differentiated 10 assigned subtypes, 3a-3i and
      3k, and two additional lineages within genotype 3. From the data of this study,
      HCV-3 full-length sequences are now available for six of the assigned subtypes
      and one unassigned. Our findings should add insights to HCV evolutionary studies
      and clinical applications.

PMID- 23152371
TI  - Upregulation of TRIM5alpha gene expression after live-attenuated simian
      immunodeficiency virus vaccination in Mauritian cynomolgus macaques, but
      TRIM5alpha genotype has no impact on virus acquisition or vaccination outcome.
AB  - Polymorphism in the TRIM5alpha/TRIMcyp gene, which interacts with the lentiviral
      capsid, has been shown to impact on simian immunodeficiency virus (SIV)
      replication in certain macaque species. Here, in the context of a live-attenuated
      SIV vaccine study conducted in Mauritian-origin cynomolgus macaques (MCM), we
      demonstrate upregulation of TRIM5alpha expression in multiple lymphoid tissues
      immediately following vaccination. Despite this, the restricted range of
      TRIM5alpha genotypes and lack of TRIMcyp variants had no or only limited impact
      on the replication kinetics in vivo of either the SIVmac viral vaccine or wild
      type SIVsmE660 challenge. Additionally, there appeared to be no impact of
      TRIM5alpha genotype on the outcome of homologous or heterologous
      vaccination/challenge studies. The limited spectrum of TRIM5alpha polymorphism in
      MCM appears to minimize host bias to provide consistency of replication for
      SIVmac/SIVsm viruses in vivo, and therefore on vaccination and pathogenesis
      studies conducted in this species.

PMID- 23152372
TI  - Fig mosaic emaravirus p4 protein is involved in cell-to-cell movement.
AB  - Fig mosaic virus (FMV), a member of the newly formed genus Emaravirus, is a
      segmented negative-strand RNA virus. Each of the six genomic FMV segments
      contains a single ORF: that of RNA4 encodes the protein p4. FMV-p4 is presumed to
      be the movement protein (MP) of the virus; however, direct experimental evidence
      for this is lacking. We assessed the intercellular distribution of FMV-p4 in
      plant cells by confocal laser scanning microscopy and we found that FMV-p4 was
      localized to plasmodesmata and to the plasma membrane accompanied by tubule-like
      structures. A series of experiments designed to examine the movement functions
      revealed that FMV-p4 has the capacity to complement viral cell-to-cell movement,
      prompt GFP diffusion between cells, and spread by itself to neighbouring cells.
      Altogether, our findings demonstrated that FMV-p4 shares several properties with
      other viral MPs and plays an important role in cell-to-cell movement.

PMID- 23152373
TI  - Colesevelam improved lipoprotein particle subclasses in patients with prediabetes
      and primary hyperlipidaemia.
AB  - BACKGROUND: A randomised, double-blind, placebo-controlled study evaluated lipid-
      and glucose-lowering effects of colesevelam in patients with prediabetes and
      primary hyperlipidaemia. We report the effect of colesevelam on lipoprotein
      particle concentration and particle size (determined by nuclear magnetic
      resonance spectroscopy) in these patients. METHODS: Adults with prediabetes
      (World Health Organization criteria), low-density lipoprotein cholesterol (LDL-C)
      >= 100 mg/dL (>=2.6 mmol/L) and triglycerides < 500 mg/dL (<5.6 mmol/L) were
      randomised to colesevelam 3.75 g/day or placebo for 16 weeks. The intent-to-treat
      population comprised 103 colesevelam and 106 placebo recipients. RESULTS: At the
      end of the study, mean reduction from baseline in total LDL particle
      concentration was significantly greater with colesevelam versus placebo (mean
      treatment difference: -113 nmol/L; p = 0.02). Increases in total very low-density
      lipoprotein particle concentration (VLDL-P) and high-density lipoprotein particle
      concentration (HDL-P) did not differ significantly between the groups; however,
      with colesevelam versus placebo, there were significantly (p < 0.05) greater
      increases in large and medium VLDL-P and large HDL-P and reductions in small VLDL
      P. Mean size increases were significantly greater with colesevelam for VLDL (mean
      treatment difference: 5.3 nm; p < 0.0001) and HDL (0.1 nm; p = 0.002).
      CONCLUSIONS: Colesevelam improved the overall atherogenic lipoprotein profile in
      adults with prediabetes and primary hyperlipidaemia, despite potentially less
      favourable changes in VLDL particles.

PMID- 23152374
TI  - Effects of oral and intraperitoneal magnesium treatment against cadmium-induced
      oxidative stress in plasma of rats.
AB  - Cadmium (Cd) has been recognised as one of the most important environmental and
      industrial pollutants, and up-to-date investigations have shown that one of the
      mechanisms of its toxicity is associated with the induction of oxidative stress.
      The aim of this study was to determine the connection between acute oral and
      intraperitoneal exposure to Cd and parameters indicative of oxidative stress in
      the plasma of rats, as well as to examine the potential protective effect of
      magnesium (Mg) in conditions of acute oral and intraperitoneal Cd poisoning. The
      experiment was performed on male albino Wistar rats (n=40) randomly divided into
      control group, Cdor group that received 30 mg kg-1 b.w. Cd by oral gavage,
      Cd+Mgor group that orally received 50 mg kg-1 b.w. Mg one hour before oral Cd,
      Cdip group that received 1.5 mg kg-1 b.w. Cd intraperitoneally, and Cd+Mgip group
      that intraperitoneally received 3 mg kg-1 b.w. Mg 10 min before intraperitoneal
      Cd. The animals were sacrificed 24 h after treatment and the following parameters
      were measured: superoxide dismutase activity, superoxide anion, total oxidative
      status, advanced oxidation protein products, and malondialdehyde. All parameters
      of oxidative stress in rat plasma were negatively affected by Cd treatment with
      more pronounced negative effects after intraperitoneal treatment, with the
      exception of superoxide dismutase (SOD) activity. Although both oral and
      intraperitoneal Mg pretreatment had protective effects, more pronounced
      beneficial effects were observed after oral administration, since it managed to
      completely prevent Cd-induced changes in the investigated parameters. The
      observed results support the use of Mg as potential protective agent against
      toxic effects caused by Cd.

PMID- 23152375
TI  - Combined effects of cadmium and decabrominated diphenyl ether on thyroid hormones
      in rats.
AB  - The aim of this study was to see how a mixture of cadmium (Cd) and decabrominated
      diphenyl ether (BDE209) affect thyroid function, namely thyroid-stimulating
      hormone (TSH), thyroxin (T4), free thyroxin (FT4), triiodothyronin (T3), and free
      triiodothyronin (FT3) in Wistar rats (eight per group) receiving either a single
      substance or their combination by gavage for 28 days. Three groups were receiving
      Cd alone in the doses of 2.5 mg kg-1, 7.5 mg kg-1, or 15 mg kg-1 b. w. a day,
      three groups were receiving BDE209 in the doses of 1000 mg kg-1, 2000 mg kg-1, or
      4000 mg kg-1 b. w. a day, while nine groups were receiving different mixtures of
      Cd and BDE209 in these doses (3x3 design). The results have indicated that the
      Cd+BDE209 mixtures more potently disrupt thyroid hormone homeostasis than would
      be expected from these chemicals alone.

PMID- 23152376
TI  - Protective effects of dietary fibre against manganese-induced neurobehavioral
      aberrations in rats.
AB  - We tested the hypothesis that dietary fibre (DF) has protective effects against
      manganese (Mn)-induced neurotoxicity. Forty-eight one-month old Sprague-Dawley
      rats were randomly divided into six groups: control, 16 % DF, Mn (50 mg kg-1 body
      weight), Mn+ 4 % DF, Mn+ 8 % DF, and Mn+ 16 % DF. After oral administration of Mn
      (as MnCl2) by intragastric tube during one month, we determined Mn concentrations
      in the blood, liver, cerebral cortex, and stool and tested neurobehavioral
      functions. Administration of Mn was associated with increased Mn concentration in
      the blood, liver, and cerebral cortex and increased Mn excretion in the stool.
      Aberrations in neurobehavioral performance included increases in escape latency
      and number of errors and decrease in step-down latency. Irrespective of the
      applied dose, the addition of DF in forage decreased tissue Mn concentrations and
      increased Mn excretion rate in the stool by 20 % to 35 %. All neurobehavioral
      aberrations were also improved. Our findings show that oral exposure to Mn may
      cause neurobehavioral abnormalities in adult rats that could be efficiently
      alleviated by concomitant supplementation of DF in animal feed.

PMID- 23152377
TI  - Altered canonical hedgehog-gli signalling axis in pesticide-induced bone marrow
      aplasia mouse model.
AB  - The mechanistic interplay between pesticide exposure and development of marrow
      aplasia is not yet well established but there are indices that chronic pesticide
      exposure in some instances causes marrow aplasia like haematopoietic degenerative
      condition in human beings. Canonical Hedgehog (Hh) signalling has multiple roles
      in a wide range of developmental processes, including haematopoiesis. The present
      study was designed to explore the status of four important components of the
      canonical Hedgehog signalling cascade, the Sonic Hedgehog (Shh), Ptch1, Smo, and
      Gli1, in a mouse model of chronic pesticide-induced bone marrow aplasia. We used
      5 % aqueous mixture of pesticides (chlorpyriphos, prophenophos, cypermethrin,
      alpha-methrin, and hexaconazole) for inhalation and dermal exposure of 6 hours
      per day and 5 days a week up to 90 days. Murine bone marrow aplasia related to
      chronic pesticide treatment was confirmed primarily by haemogram, bone marrow
      cellularity, short term bone marrow explant culture for cellular kinetics, bone
      marrow smear, and fl ow cytometric Lin-Sca-1+C-kit+ extracellular receptor
      expression pattern. Later, components of hedgehog signalling were analysed in the
      bone marrow of both control and pesticide-treated aplastic groups of animals. The
      results depicted pancytopenic feature of peripheral blood, developmental anomaly
      of neutrophils, depression of primitive stem and progenitor population along with
      Shh, Ptch1, Smo and Gli1 expression in aplasia group. This investigation suggests
      that pesticide-induced downregulation of two critically important proteins--Ptch1
      and Gli1--inside the haematopoietic stem and progenitor cell population impairs
      haematopoietic homeostasis and regeneration mechanism in vivo concurrent with
      bone marrow aplasia.

PMID- 23152378
TI  - Prediction of mutagenicity, carcinogenicity, developmental toxicity, and skin
      sensitisation with Caesar program for a set of conazoles.
AB  - This article presents models to predict mutagenicity, carcinogenicity,
      developmental toxicity, and skin sensitisation for a set of 27 conazoles. The
      predictions were performed with the program package CAESAR, which is available on
      the Internet. The CAESAR programs were developed to support the European
      Community Regulation on chemicals and their safe use (REACH) and follow the OECD
      principles for (Q)SAR models used for regulatory purposes. The programs provide a
      number of information, including a binary classification of a compound as toxic
      or non-toxic and information on similar compounds from the model's training sets
      (similarity sets). In this study we analysed conazole sets using principal
      component analysis (PCA). The predictions were compared to the currently valid
      classification of these substances in the European Union (EU) or to the
      classification proposed at expert meetings of the Pesticide Risk Assessment and
      Peer Review (PRAPeR) group. The predicted classification for mutagenicity was in
      good agreement with regulatory classification, the predictions for
      carcinogenicity and developmental toxicity showed some discrepancy in particular
      cases, while the predictions for skin sensitisation showed even greater
      discrepancy.

PMID- 23152379
TI  - Comparison of buffers for extraction of mite allergen der p 1 from dust.
AB  - Der p 1 is the main allergen of house dust mite Dermatophagoides pteronyssinus,
      which has routinely been detected in residential dust. However, the procedure for
      extracting Der p 1 from reservoir dust has not been well defined. The aim of this
      study was to compare Der p 1 mass fractions in dust extracts prepared using the
      following extraction buffers: phosphate (pH 7.4), borate (pH 8.0), and ammonium
      bicarbonate (pH 8.0), all with 0.05 % Tween 20. Twenty-eight dust samples were
      divided into three aliquots and each portion was extracted with one of the three
      buffers at room temperature. Der p 1 mass fractions were measured in a total of
      84 dust extracts using the enzyme immunoassay (range: 0.1 MUg g-1 to 7.53 MUg g
      1). Statistical methods including intraclass correlation showed a high agreement
      between Der p 1 mass fractions irrespective of the extracting medium. Our results
      suggest that all three buffers are suitable for the extraction of mite allergens
      and routine Der p 1 analysis in dust.

PMID- 23152380
TI  - Sulphur cycling between terrestrial agroecosystem and atmosphere.
AB  - Central gas station of the natural gas borehole system Podravina is located near
      the village Molve. It delivers more than a quarter of total energy used in
      Croatia to its consumers. Over the years, adapting technology to increasingly
      demanding and rigorous standards in environmental protection has become
      paramount. Yet, despite all the industry has undertaken to address the risk of
      harmful substances entering the food chain, a multidisciplinary research team of
      independent scientists monitors the content of specific substances in all
      components of the ecosystem. This paper presents measurements of total sulphur
      contents in soil surface [(0 to 3) cm] and subsurface [(3 to 8) cm] layers (study
      period: autumn 2006 - spring 2010) and in plants (study period: spring 2000 -
      spring 2010), and the concentration of gaseous sulphur compounds in the air.
      Concentrations of hydrogen sulphide (H2S) and mercaptans (RSH) were measured from
      the summer of 2002 until the autumn of 2010, while concentrations of sulphur
      dioxide (SO2) were measured from the spring of 2008 until the autumn of 2010. The
      paper also shows total annual atmospheric sulphur (S-SO4) deposition at Bilogora
      measuring station (study period: 2001 - 2010). Average monthly concentrations of
      H2S in air varied between 0.2 MUg m-3 and 2.0 MUg m-3, RSH between 0.1 MUg m-3
      and 24.5 MUg m-3, and SO2 between 0.4 MUg m-3 and 2.8 MUg m-3 depending on the
      location and the season of sampling. Mean values of total sulphur in soil and in
      Plantago lanceolata plant ranged between 610 mg kg-1 and 1,599 mg kg-1 and
      between 3,614 mg kg-1 and 4,342 mg kg-1, respectively, depending on the soil
      type, location, and sampling depth. Average values of total sulphur mass ratio
      for all examined single soil samples (n=80) were 1,080 mg kg-1 for both studied
      layers, and 4,108 mg kg-1 for all analysed plant samples (n=85). Average total
      annual atmospheric sulphur deposition at Bilogora measuring station was 6.3 kg of
      S-SO4 per hectare.

PMID- 23152381
TI  - Associations between weather conditions and ragweed pollen variations in Szeged,
      Hungary.
AB  - This study analyses potential associations between day-to-day variations in
      common ragweed pollen counts in the southern Hungarian district of Szeged and
      meteorological variables using adapted factor analysis. The database includes ten
      years (1997-2006) worth of data on daily common ragweed pollen ratios (value on
      the given day per value on the day before) and daily differences (value on the
      given day minus value on the day before) in eight meteorological variables (mean
      temperature, minimum temperature, maximum temperature, temperature range,
      irradiance, relative humidity, wind speed, and rainfall) over the ragweed pollen
      season. This method is new, as it has only been applied in the economics. In
      factor analysis it is advisable to combine all the weights of the factors and the
      resultant variable into one factor indicating the rank of importance of the given
      explanatory variables in influencing the resultant variable, while the remaining
      factors are uncorrelated with the resultant variable. The procedure shows that
      wind speed, rainfall, and temperature range are the most important, while minimum
      temperature and irradiance are the least important meteorological variables
      influencing daily pollen ratios. We found a tendency to stronger associations
      between the meteorological variables and the pollen variable when the pollen
      ratio was 1 or below. This is due to the fact that data corresponding to the
      pollen ratio over 1 come mainly from the prepeak pollen season, while data
      corresponding to less than 1 are characteristic of the post-peak pollen season
      (late summer to early autumn).

PMID- 23152382
TI  - Cadmium and zinc induced similar changes in protein and glycoprotein patterns in
      tobacco (Nicotiana tabacum l.) seedlings and plants.
AB  - The effects of 10 MUmol L-1 and 15 MUmol L-1 cadmium (Cd), a nonessential toxic
      element and 25 MUmol L-1 and 50 MUmol L-1 zinc (Zn), an essential micronutrient,
      on proteins and glycoproteins of Nicotiana tabacum L. seedlings and plants were
      investigated after exposure to each metal alone or to their combinations. Changes
      in only few polypeptides related to heavy metal treatments were observed in
      tobacco seedlings and leaves of adult plants, while the greatest change in total
      soluble protein pattern was observed in plant roots. Differences between control
      and treated tobacco tissues were more pronounced in the glycoprotein pattern,
      which was analysed by application of different lectins. The majority of the
      detected glycoproteins in leaves and roots of adult plants can be considered as a
      result of enhanced glycosylation due to heavy metal stress. The difference in
      glycoproteins between Cd and Zn application on tobacco seedlings and adult plants
      could not be determined since enhanced glycosylation was noticed after treatment
      with either metal alone or in combination. Therefore, it can be concluded that
      both metals induced N- and Oglycosylation as a result of changed environmental
      conditions.

PMID- 23152383
TI  - Inertisation of galvanic sludge with calcium oxide, activated carbon, and
      phosphoric acid.
AB  - In this study we compared three methods for the treatment of electroplating
      sludge highly loaded with zinc and iron: (1) calcium oxide-based
      solidification/stabilisation; (2) conversion into inert material by adsorption of
      organic and inorganic pollutants onto activated carbon; and (3) conversion of
      mobile waste components into insoluble phosphates. All three methods proved
      highly efficient in the conversion of hazardous waste into inert material. Under
      optimum treatment conditions zinc concentration in the leachate of solidified
      waste was reduced by 99.7 % compared to untreated sludge. Zinc retention
      efficiency in the waste treated with activated carbon and phosphoric acid was
      99.9 % and 98.7 %, respectively. The advantages of electroplating sludge
      treatment with activated carbon over the other two methods are high sorption
      capacity, insignificant pH and volume changes of the sludge, and simple use.

PMID- 23152384
TI  - COPD and occupation: a retrospective cohort study of industrial workers.
AB  - The aim of this paper was to ascertain chronic obstructive pulmonary disease
      (COPD) prevalence among industrial workers in the Russian Federation and
      determine relative contribution of smoking and occupational factors to COPD. We
      recruited 1,375 workers aged 30 or over. Six hundred and twenty-four of them were
      occupationally exposed to vapours, gases, dust, and fumes (VGDF). Physical
      examination and baseline spirometry were performed for all the participants of
      the study. Those with airfl ow limitation of FEV1/FVC<0.70 were considered having
      COPD and those with presence of cough and sputum production for at least three
      months in each of two consecutive years were considered having chronic bronchitis
      (CB), with no overlapping between these 2 groups. Data on occupational history
      and VGDF levels in the working area were collected from all participants. In
      total, 105 cases of COPD and 170 cases of CB were diagnosed in the cohort of
      examined workers. Occupational exposure to VGDF was twice as often present among
      COPD patients than among both patients with CB and the control group of healthy
      workers (p<0.05). More than 40 % of COPD patients were occupationally exposed to
      VGDF above the value of 3.0 of the occupational exposure limit (OEL) and more
      than 20 % to 6.0 OEL and higher. Overall odds ratio for COPD development due to
      occupational VGDF exposure was 5.9 (95 % CI=3.6 to 9.8, p=0.0001). Both smoking
      and VGDF seem to be important for the development of COPD. Analysis of the
      combined effect of tobacco smoking and occupational noxious particles and gases
      on COPD development has shown the following order of risk factors based on the
      strength of their infl uence: VGDF levels, smoking index, age, and heating
      microclimate. There is a statistically signifi cant level of relationship and
      "dose-effect" dependence between occupational exposures to VGDF and the
      development of COPD. The effect of VGDF composition on the probability of COPD
      development was not found in the study. Results of this study were used to
      substantiate the inclusion of COPD into the National List of Occupational
      Diseases of the Russian Federation.

PMID- 23152385
TI  - Chronic effects of environmental biomass smoke on lung histopathology in Turkish
      non-smoking women: a case series.
AB  - Biomass is widely used for fuel in developing countries. Particles and gases of
      biomass burning may cause changes in the lung. In this prospective study we
      investigated histopathological changes in the lungs of 42 non-smoking women [mean
      age (59+/-10) years] caused by biomass smoke. We valuated exposure to biomass
      smoke, case histories, and the findings of physical examination, radiology,
      bronchoscopy, and lung histopathology. Mean exposure to biomass smoke was (28+/
      9) hour-year (1 hour-year equals 365 hours of exposure per year with average
      exposure of 1 hour a day). The radiological findings were mass (42 %),
      reticulonodular opacities (31 %), mediastinal lymphadenopathy (26 %), pleuro
      parenchymal fibrotic banding (19 %), widening of the pulmonary artery (14 %),
      ground glass (11 %), mosaic perfusion (9 %), consolidation (9 %), segmental or
      subsegmental atelectasis (7 %), and bronchiectasis (7 %). The patients were
      diagnosed with lung cancer (35 %), interstitial lung disease (31 %), sarcoidosis
      (9 %), tuberculosis (9 %), chronic obstructive pulmonary disease (4 %), chronic
      bronchitis (9 %), and metastasis (4 %). Bronchoscopy showed pilies, oedema,
      erythema, bronchus narrowing, endobronchial tumour, mucosal irregularity,
      increased vascularisation, blue-black anthracotic plaques, mucosal oedema, and
      purulent secretion. Transbronchial biopsies revealed neutrophil and lymphocyte
      leucocytes in the perivascular, peribronchiolar, and interalveolar septa,
      slightly enlarged connective tissue, thickening of the basal membrane, thickening
      of interalveolar septa, intimal and medial thickening of the vascular wall and
      vascular lumen narrowing, anthracosis between the cells and in the bronchiole
      epithelium. These findings confirm that biomass smoke has important toxic effects
      on the lung parenchyma, interstitium, and pulmonary vessels that may result in
      malignancies.

PMID- 23152386
TI  - Chromosomal instability in peripheral blood lymphocytes of patients with
      reproductive failure assessed by micronucleus assay.
AB  - We investigated chromosomal instability in peripheral blood lymphocytes (PBL) of
      patients with reproductive failure in respect to age, smoking habits, gender,
      miscarriages, and semen parameters. The study involved 36 individual cases of
      reproductive failure (18 men and 18 women) attended at the Clinical Centre of
      Kragujevac, Serbia, and 30 healthy subjects (15 men and 15 women). Micronuclei
      (MN) frequency was estimated in PBL using the cytokinesis-block micronucleus
      (CBMN) assay. The baseline MN frequencies were significantly higher (p=0.031;
      p<0.001) in male [(9.22 +/- 4.70) MN per 1000 BN cells] and female patients
      [(13.50 +/- 2.5) MN per 1000 BN cells] than in male and female healthy controls
      [(6.27 +/- 2.66) MN per 1000 BN cells; (6.80 +/- 2.98) MN per 1000 BN cells]. The
      mean baseline MN frequency did not significantly differ between miscarriage
      groups and between patients with and without normal values of semen parameters.
      The correlations between poor sperm concentration (<20x106 mL-1), rapid
      progressive motility (<25 %), normal morphology (<30 %), and MN frequencies were
      negative, but not statistically significant. We found that only gender
      significantly influenced the MN rates in analysed patients. There were no
      significant differences between age groups and between smokers and non-smokers in
      patients and control samples. We conclude that the increase in baseline MN
      frequency in PBL of patients with reproductive failure corresponds to the
      increase in chromosomal damage, which occurs as a result of complex events that
      cause reproductive disorders.

PMID- 23152387
TI  - Monocrotophos poisoning through contaminated millet flour.
AB  - Several episodes of mass poisoning by organophosphates (OPs) have been reported
      from the developing countries. The diagnosis of OP-poisoning is mainly based on
      the characteristic clinical features and history of exposure to a known OP
      compound. Estimation of serum and red blood cell (RBC) cholinesterase activities
      are helpful in confirming the diagnosis. However, there is controversy regarding
      a definite relationship between serum cholinesterase activity and the severity of
      clinical manifestations and prognosis. This report describes an episode of mass
      monocrotophos poisoning that occurred due to accidental ingestion of
      monocrotophos-contaminated millet (so-called bavta) flour involving eight
      severely poisoned persons. Clinical presentation included severe abdominal pain,
      diarrhoea, vomiting, pupil narrowing, and difficulty breathing. On hospital
      admission, plasma cholinesterase (PChE) and especially RBC acetylcholinesterase
      (AChE) activities correlated well with clinical symptoms presented by the
      patients. This case study highlights the need for clinicians to be aware of OP
      pesticide poisoning from food sources and the need to look for depressed PChE and
      AChE activities that may point to OP exposure, so that OP-poisoning can be
      identified immediately and patients can receive specific treatment, rather than
      general treatment for food poisoning.

PMID- 23152388
TI  - [Delays in diagnosing and treating tuberculosis in Croatia].
AB  - The aim of this study was to determine factors causing delay in tuberculosis
      diagnosis and treatment in Croatia. It included 240 adults with pulmonary
      tuberculosis, who were interviewed for demographics, socioeconomic, lifestyle,
      and personal health data. Total delay was defined as a number of days from the
      onset of symptoms to the initiation of therapy. The median and the 75th
      percentile of the total delay were 68 and 120 days, respectively: 16.7 % of the
      patients initiated treatment within the first month, 23.8 % within the second
      month, 23.3 % within the third month, 12.9 % within the fourth month, and 23.3 %
      more than four months after the symptoms appeared. Long delay (exceeding median
      delay) was strongly associated with drug abuse (p=0.021). Extreme delay (75th
      percentile of delay) was significantly associated with the lowest level of
      education (p=0.021), below minimal income (p=0.039), minimal to average income
      (p=0.020), current smoking (p=0.050), and co-morbidity (p=0.048). In the
      multivariate model, long delay remained associated with drug abuse, while extreme
      delay was associated with the lowest level of education (p=0.033) and current
      (p=0.017) and ex-smoking (p=0.045).In a setting with decreasing TB incidence, the
      reported delay can be reduced by increasing health education, not only about
      tuberculosis per se, but about health in general and attitudes towards prevention
      and early care. It is also important to increase tuberculosis knowledge among
      healthcare workers as well as their diagnostic skills.

PMID- 23152389
TI  - Obesity: genome and environment interactions.
AB  - Obesity has become one of the major threats for public health in industrialised
      world among adults, but also among adolescents and children. It is influenced by
      the interaction of genes, nutrition, environment, and lifestyle. Environmental
      and lifestyle risk factors include foetal and lifelong environment, nutrient
      quality, chemical and microbial exposure, and psychical stress, all of which are
      important contributing influences. Removing or limiting chemical and
      pharmaceutical obesogens from human environment could make a difference in the
      growing epidemic of obesity. Additionally, nutrigenomics describes how
      modifications in individual diets can improve health and prevent chronic
      diseases, as well as obesity, by understanding the effects of a genetic profile
      in the interaction between food and increase in body weight. Furthermore,
      individual genetic variations in genome represent an individual's predisposition
      for obesity. Therefore, the use of individual genetic information, avoiding
      obesogens, and a healthy lifestyle could help to improve the management of
      obesity and maintain a healthy weight.

PMID- 23152390
TI  - Biological indicators in response to radiofrequency/microwave exposure.
AB  - Over the years, due to rapid technological progress, radiation from man-made
      sources exceeded that of natural origin. There is a general concern regarding a
      growing number of appliances that use radiofrequency/ microwave (RF/MW) radiation
      with particular emphasis on mobile communication systems. Since nonthermal
      biological effects and mechanisms of RF/MW radiation are still uncertain,
      laboratory studies on animal models, tissues, cells, and cell free system are of
      extraordinary importance in bioelectromagnetic research. We believe that such
      investigations play a supporting role in public risk assessment. Cellular systems
      with the potential for a clear response to RF/MW exposures should be used in
      those studies. It is known that organism is a complex electrochemical system
      where processes of oxidation and reduction regularly occur. One of the plausible
      mechanisms is connected with generation of reactive oxygen species (ROS).
      Depending on concentration, ROS can have both beneficial and deleterious effects.
      Positive effects are connected with cell signalling, defence against infectious
      agents, and proliferative cell ability. On the other hand, excessive production,
      which overloads antioxidant defence mechanism, leads to cellular damage with
      serious potential for disease development. ROS concentration increase within the
      cell caused by RF/MW radiation seems to be a biologically relevant hypothesis to
      give clear insight into the RF/MW action at non-thermal level of radiation. In
      order to better understand the exact mechanism of action and its consequences,
      further research is needed in the field. We would like to present current
      knowledge on possible biological mechanisms of RF/MW actions.

PMID- 23152399
TI  - Correlation of pull-out strength of cement-augmented pedicle screws with CT
      volumetric measurement of cement.
AB  - BACKGROUND: Cement augmentation of pedicle screws increases fixation strength in
      an osteoporotic spine. This study was designed to determine the cement
      distribution and the correlation between the pull-out strength of the augmented
      screw and the cement volume within polyurethane (PU) foam. METHODS: Twenty-eight
      cannulated pedicle screws (6*45 mm) (Peter Brehm, Erlangen, Germany) with four
      holes at the distal end of the screw were augmented with the acrylic Stabilit ER
      Bone Cement Vertebral Augmentation System (DFine Inc., San Jose, CA, USA) and
      implanted into open-cell rigid PU foam (Pacific Research Laboratories, Vashon
      Island, WA, USA) with a density of 0.12 g/cm3, resembling severe osteoporosis.
      Volumetric measurement of the cement with consideration of the distribution
      around the screws was done with multislice computed tomography scan (Somatom
      Definition, Siemens, Erlangen, Germany). Pull-out strength was tested with a
      servohydraulic system (MTS System Corporation, Eden Prairie, MN, USA), and
      nonaugmented screws served as control. Pearson's correlation coefficient with
      significance level alpha=0.05 and one-way analysis of variance test were used.
      RESULTS: We found a high (r=0.88) and significant (p<0.01) correlation between
      the cement volume and the pull-out strength, which increased by more than 5-fold
      with a volume of 3 ml. The correlation appeared linear at least up to 4 ml cement
      volume and failure always occurred at the cement-bone interface. The cement
      distribution was symmetric and circular around the most proximal hole, with a
      distance of 14 mm from the tip, and nearly 90% of the cement was found 6 mm
      distal and cranial to it. The 95% confidence interval for the relative amount of
      cement was 37%-41% within 2 mm of the most proximal hole. CONCLUSION: Compared
      with the control, a cement volume between 2.0 and 3.0 ml increased the pull-out
      strength significantly and is relevant for clinical purposes, whereas a volume of
      0.5 ml did not. A cement volume beyond 3.0 ml should further increase the pull
      out strength because the correlation was linear at least up to 4.0 ml, but the
      possibility of in vivo cement leakage with increasing volume has to be
      considered. Pressure-controlled cement application might be a tool to avoid this
      complication. The cement almost completely penetrated the most proximal
      perforation.

PMID- 23152400
TI  - Dissecting circuit mechanisms by genetic manipulation of specific neural
      pathways.
AB  - The major issue in neuroscience is to delineate the structure and function of the
      neural circuits that mediate a variety of brain functions. One useful approach to
      resolve this issue is the genetic manipulation of the activity of specific neural
      circuits, which enables the study of the behavioral and physiological
      consequences of the manipulation. A novel type of lentiviral vector showing
      highly efficient retrograde gene transfer (HiRet) can introduce a transgene into
      neurons that innervate a certain brain region at the vector injection site and
      confer a fundamental tool for genetically manipulating specific neural pathways.
      Here, we describe the strategy for the selective targeting of neural pathways by
      using this HiRet vector, combined with immunotoxin (IT)-mediated cell targeting,
      which eliminates particular neuronal types genetically engineered to express a
      receptor for the recombinant IT. Our strategy provides a powerful technology to
      investigate the framework underlying brain functions and to develop animal models
      for the dissection of neurological and neuropsychiatric diseases.

PMID- 23152401
TI  - Multiple sclerosis and glutamate excitotoxicity.
AB  - The previous understanding of multiple sclerosis was solely related to
      neuroinflammation and its harmful effects; however, countless data indicate the
      importance of some inflammation-independent, neurodegenerative mechanisms
      associated with mitochondria malfunction, iron deposition and oxidative stress.
      Recently, it has been postulated that glutamate excitotoxicity, a phenomenon that
      takes place when an excessive amount of glutamate overactivates its cellular
      receptors and induces cell death, could be a missing link between inflammatory
      and neurodegenerative processes evident in multiple sclerosis. Glutamate is the
      major excitatory neurotransmitter of the central nervous system, which has been
      proven to have a central role in a complex communication network established
      between all residential brain cells, including neurons, astrocytes,
      oligodendrocytes and microglia. Thus, the disturbance of glutamate homeostasis
      could affect practically all physiological functions and interactions of brain
      cells, leading to heterogeneity of pathological events. The understanding of
      glutamate excitotoxicity as a valid mechanism of central nervous system damage in
      multiple sclerosis, requires the revision of the current knowledge about a source
      of elevated extracellular glutamate, glutamate receptor alterations, alterations
      of glutamate transporters and metabolizing enzymes, as well as molecular
      mechanism of excitotoxic damage.

PMID- 23152402
TI  - In silico pharmacology for a multidisciplinary drug discovery process.
AB  - The process of bringing new and innovative drugs, from conception and synthesis
      through to approval on the market can take the pharmaceutical industry 8-15 years
      and cost approximately $1.8 billion. Two key technologies are improving the hit
      to-drug timeline: high-throughput screening (HTS) and rational drug design. In
      the latter case, starting from some known ligand-based or target-based
      information, a lead structure will be rationally designed to be tested in vitro
      or in vivo. Computational methods are part of many drug discovery programs,
      including the assessment of ADME (absorption-distribution-metabolism-excretion)
      and toxicity (ADMET) properties of compounds at the early stages of
      discovery/development with impressive results. The aim of this paper is to
      review, in a simple way, some of the most popular strategies used by modelers and
      some successful applications on computational chemistry to raise awareness of its
      importance and potential for an actual multidisciplinary drug discovery process.

PMID- 23152403
TI  - Cytochrome P450 2B6: function, genetics, and clinical relevance.
AB  - Cytochrome P450 (CYP) 2B6 belongs to the set of important hepatic drug
      metabolizing CYPs. It makes up roughly 3%-6% of total hepatic CYP content and
      metabolizes several pharmaceuticals including bupropion, efavirenz,
      cyclophosphamide, pethidine, ketamine and propofol. The enzyme is susceptible to
      drug-drug interactions by enzyme induction and inhibition. In addition to drugs,
      CYP2B6 is able to both detoxify and bioactivate a number of procarcinogens and
      environmental agents including pesticides and herbicides. There is an extensive
      interindividual variability in the expression of CYP2B6, which is in part
      explained by extensive genetic polymorphism. CYP2B6 is one of the most
      polymorphic CYP genes in humans with over 100 described SNPs, numerous complex
      haplotypes and distinct ethnic and racial frequencies. This review summarizes the
      basic properties of CYP2B6 and the main characteristics of clinical relevance.

PMID- 23152404
TI  - The proinflammatory cytokines interleukin-1alpha and tumor necrosis factor alpha
      promote the expression and secretion of proteolytically active cathepsin S from
      human chondrocytes.
AB  - Osteoarthritis and rheumatoid arthritis are destructive joint diseases that
      involve the loss of articular cartilage. Degradation of cartilage extracellular
      matrix is believed to occur due to imbalance between the catabolic and anabolic
      processes of resident chondrocytes. Previous work has suggested that various
      lysosomal cysteine cathepsins participate in cartilage degeneration; however,
      their exact roles in disease development and progression have not been
      elucidated. In order to study degradation processes under conditions resembling
      the in vivo milieu of the cartilage, we cultivated chondrocytes on a type II
      collagen-containing matrix. Stimulation of the cultivated chondrocytes with
      interleukin-1alpha and/or tumor necrosis factor alpha resulted in a time
      dependent increase in cathepsin S expression and induced its secretion into the
      conditioned media. Using a novel bioluminescent activity-based probe, we were
      able to demonstrate a significant increase in proteolytic activity of cathepsin S
      in the conditioned media of proinflammatory cytokine-stimulated chondrocytes. For
      the first time, cathepsin S was demonstrated to be secreted from chondrocytes
      upon stimulation with the proinflammatory cytokines, and displayed proteolytic
      activity in culture supernatants. Its stability at neutral pH and potent
      proteolytic activity on extracellular matrix components mean that cathepsin S may
      contribute significantly to cartilage degradation and may thus be considered a
      potential drug target in joint diseases.

PMID- 23152405
TI  - Pro-angiogenic effect of human kallikrein-related peptidase 12 (KLK12) in lung
      endothelial cells does not depend on kinin-mediated activation of B2 receptor.
AB  - Kallikrein-12 (KLK12) may play an important role in angiogenesis modulating
      proangiogenic factor bioavailability and activating the kinin receptor B2
      pathway. We studied whether KLK12 had an impact on angiogenesis and the
      activation of kinin receptor B2 results from the KLK12-dependent generation of
      kinins. KLK12 efficiently hydrolyzed high molecular weight kininogen, liberating
      a fragment containing the carboxy-terminal end of kinins. The kininogenase
      activity of KLK12 was poor, however, due to the cleavage resistance of the N
      terminal side of the kinin sequence. A very low amount of kinins was accordingly
      released after in vitro incubation of high molecular weight kininogen with KLK12
      and thus the proangiogenic activity of KLK12 in lung endothelial cells was not
      related to a kinin release.

PMID- 23152407
TI  - Interactions between BdkrB2 and p53 genes in the developing kidney.
AB  - Gene-environment interactions are implicated in congenital disorders.
      Accordingly, there is a pressing need to develop animal models of human disease,
      which are the product of defined gene-environment interactions. Work from our
      laboratory demonstrates the presence of genetic interactions between the
      bradykinin B2 receptor (BdkrB2) and the tumor suppressor protein p53 in the
      developing kidney. Our studies have shown that the Bdkrb2(-/-) embryos exposed to
      gestational salt stress develop renal dysgenesis. The underlying mechanism is p53
      stabilization and mediated apoptosis and repression of the terminal epithelial
      differentiation program. We also uncovered a novel functional cross-talk between
      p53 and BdkrB2. Thus, while BdkrB2 is a target for p53-mediated transcriptional
      activation, BdkrB2 inactivation results in the upregulation of checkpoint kinase
      1 (Chk1) levels, thus potentiating phosphorylation of p53 on Ser23 by Chk1, an
      essential step in the pathway leading to renal dysgenesis in salt-stressed
      BdkrB2(-/-) mutant mice. Future studies will now focus on defining how this G
      protein-coupled receptor is coupled to the activation of p53, a tumor suppressor
      gene that is mutated in more than 50% of all human cancers.

PMID- 23152406
TI  - Melanoma resistance to photodynamic therapy: new insights.
AB  - Melanoma is the most dangerous form of skin cancer, with a steeply rising
      incidence and a poor prognosis in its advanced stages. Melanoma is highly
      resistant to traditional chemotherapy and radiotherapy, although modern targeted
      therapies such as BRAF inhibitors are showing some promise. Photodynamic therapy
      (PDT, the combination of photosensitizing dyes and visible light) has been tested
      in the treatment of melanoma with some promising results, but melanoma is
      generally considered to be resistant to it. Optical interference by the highly
      pigmented melanin, the antioxidant effect of melanin, the sequestration of
      photosensitizers inside melanosomes, defects in apoptotic pathways, and the
      efflux of photosensitizers by ATP-binding cassette transporters have all been
      implicated in melanoma resistance to PDT. Approaches to overcoming melanoma
      resistance to PDT include: the discovery of highly active photosensitizers
      absorbing in the 700-800-nm near infrared spectral region; interventions that can
      temporarily reduce the amount or pigmentation of the melanin; compounds that can
      reverse apoptotic defects or inhibit drug-efflux of photosensitizers; and
      immunotherapy approaches that can take advantage of the ability of PDT to
      activate the host immune system against the tumor being treated.

PMID- 23152409
TI  - Dissecting the impact of Frizzled receptors in Wnt/beta-catenin signaling of
      human mesenchymal stem cells.
AB  - Wnt/beta-catenin signaling is of fundamental importance in the regulation of self
      renewal, migration/invasion, and differentiation of human mesenchymal stem cells
      (hMSCs). Because little information is available about the function of Frizzled
      receptors (Fzds) as the main receptors of Wnt proteins in hMSCs, we first
      performed comparative Fzd mRNA expression profiling. Fzd9 and Fzd10 were not
      expressed in hMSCs. While Fzd3 was expressed at low levels in hMSCs, the other
      Fzds exhibited high expression rates. Activation and repression of Wnt signaling
      in hMSCs revealed that the expression levels of Fzd1, Fzd6, and Fzd7 are
      positively correlated with the Wnt/beta-catenin activation status, whereas Fzd8
      exhibited an inverse relation. For studying the functional relevance of Fzds in
      Wnt/beta-catenin signaling, RNA interference, ectopic expression studies, and
      rescue approaches were performed in hMSCs carrying a highly sensitive TCF/LEF
      reporter gene system (Gaussia luciferase). We found that, Fzd1, Fzd5, Fzd7, and
      Fzd8 are largely involved in Wnt/beta-catenin signaling of hMSCs. Moreover, the
      knockdown of Fzd5 can be compensated by the ectopic expression of Fzd7.
      Conversely, the ectopic expression of Fzd5 in Fzd7-knockdown hMSCs resulted in a
      rescue of Wnt/beta-catenin signaling, pointing to a functional redundancy of Fzd5
      and Fzd7.

PMID- 23152408
TI  - Effects of cathepsin K deficiency on intercellular junction proteins, luminal
      mucus layers, and extracellular matrix constituents in the mouse colon.
AB  - Cathepsin K has been shown to exhibit antimicrobial and anti-inflammatory
      activities in the mouse colon. To further elucidate its role, we used Ctsk-/-
      mice and demonstrated that the absence of cathepsin K was accompanied by elevated
      protein levels of related cysteine cathepsins (cathepsins B, L, and X) in the
      colon. In principle, such changes could result in altered subcellular
      localization; however, the trafficking of cysteine cathepsins was not affected in
      the colon of Ctsk-/- mice. However, cathepsin K deficiency affected the
      extracellular matrix constituents, as higher amounts of collagen IV and laminin
      were observed. Moreover, the localization pattern of the intercellular junction
      proteins E-cadherin and occludin was altered in the colon of Ctsk-/- mice,
      suggesting potential impairment of the barrier function. Thus, we used an ex vivo
      method for assessing the mucus layers and showed that the absence of cathepsin K
      had no influence on mucus organization and growth. The data of this study support
      the notion that cathepsin K contributes to intestinal homeostasis and tissue
      architecture, but the lack of cathepsin K activity is not expected to affect the
      mucus-depending barrier functions of the mouse colon. These results are important
      with regard to oral administration of cathepsin K inhibitors that are currently
      under investigation in clinical trials.

PMID- 23152410
TI  - IGF-I receptor phosphorylation is impaired in cathepsin X-deficient prostate
      cancer cells.
AB  - The cysteine-type peptidase cathepsin X is highly upregulated in several cancers
      and presumably promotes tumor invasion through bypassing cellular senescence.
      Here, we present first evidence that the underlying mechanism may involve the
      regulation of the insulin-like growth factor (IGF) system, a well-known activator
      of proliferating tumor cells. Cathepsin X deficiency leads to a reduced
      phosphorylation of the IGF-I receptor in response to IGF-I stimulation. In
      addition, downstream signaling through focal adhesion kinase was also affected.
      Taken together, our results indicate that cathepsin X is able to assist in IGF
      signaling, which may be an important progress toward understanding cathepsin X
      dependent tumorigenesis.

PMID- 23152411
TI  - Bioanalytical methods for quantitation of levamisole, a widespread cocaine
      adulterant.
AB  - Abstract Levamisole is an anthelminthic that was first used as a de-worming agent
      in humans and animals. It has also been used to treat inflammatory conditions as
      well as certain types of cancer. Levamisole was discontinued for human use in the
      early 21st century due to toxic side effects including agranulocytosis and
      vasculitis. Recently, levamisole was discovered as a cocaine adulterant after
      reports emerged of drug users with the above disorders. As the prevalence of
      cocaine usage has grown in the last 15 years, measurement of levamisole in human
      samples has become increasingly important. This review focuses on the various
      bioanalytical methods available for the determination of levamisole in human
      plasma and urine. Earlier methods employed gas chromatography coupled with
      nitrogen-selective thermionic specific detection and nitrogen-phosphorus
      detection, as well as high performance liquid chromatography coupled with
      ultraviolet detection. In addition, gas chromatography-mass spectrometry (GC-MS)
      and high performance liquid chromatography-tandem mass spectrometry (LC-MS/MS)
      have also been described. Currently, GC-MS appears to be the method of choice
      however recent developments in the area of LC-MS/MS make this technology an
      attractive alternative. The merits of both GC-MS and LC-MS/MS for the
      determination of levamisole are evaluated on the basis of sample preparation,
      chromatographic separation conditions, run time, and analytical performance. In
      addition, emerging methods in this area are also reviewed.

PMID- 23152412
TI  - Plasma long pentraxin 3 (PTX3) concentration is a novel marker of disease
      activity in patients with community-acquired pneumonia.
AB  - BACKGROUND: Long pentraxin 3 (PTX3) is an acute-phase protein secreted by various
      cells, including leukocytes and endothelial cells. Like C-reactive protein (CRP),
      it belongs to the pentraxin superfamily. The aim of this study was to investigate
      the differential changes in plasma levels of PTX3 between before and after
      antibiotic treatment in hospitalized adult patients with community-acquired
      pneumonia (CAP). METHODS: Plasma PTX3 levels were measured in 61 adult patients
      with CAP and 60 healthy controls using a commercial enzyme-linked immunosorbent
      assay (ELISA). Upon initial hospitalization, APACHE II, CURB-65, and pneumonia
      severity index (PSI) scores were determined to assess CAP severity in patients.
      RESULTS: The results showed a decline in the number of white blood cells (WBCs)
      and neutrophils, and decreases in the concentrations of CRP and PTX3 observed
      after antibiotic treatment. The plasma concentration of PTX3, but not CRP, was
      correlated with the severity of CAP based on the PSI (r=0.290, p=0.023), CURB-65
      (r=0.312, p=0.015), and APACHE II scores (r=0.427, p=0.001). The PTX3 level also
      exhibited a significant correlation with the length of hospital stay (r=0.500,
      p<0.0001). CONCLUSIONS: PTX3 may be able to play a role in the diagnosis and
      clinical assessment of the severity of CAP, which could potentially guide the
      development of treatment strategies.

PMID- 23152413
TI  - Time for a conceptual shift in assessment of internal quality control for whole
      blood or cell-based testing systems? An evaluation using platelet function and
      the PFA-100 as a case example.
AB  - Internal quality control (IQC) is essential to good laboratory practice. IQC for
      certain tests are, however, limited due to inherent problems in providing
      stabilized IQC material, as applicable to many whole-blood and cell-based
      systems. Paradigmatic in the hemostasis field is platelet function testing, where
      IQC processes remain at their infancy, despite such tests being undertaken for
      decades. One example is the PFA-100, a popular primary hemostasis screening
      system used to evaluate pre-surgical bleeding risk, screen for possible von
      Willebrand disease and/or platelet function disorders, and assess desmopressin
      and anti-platelet therapy; whatever application, laboratories are required to
      ensure instruments are in optimal working condition, but currently available IQC
      is limited. Accordingly, a novel test process for IQC of the PFA-100 is explored
      as an example of potential development. In brief, IQC test systems were prepared
      to yield prolonged PFA closure times (CTs) ('pathological QC') after the addition
      of normal whole blood (which provided 'normal QC'). Inter-run test systems
      coefficients of variation (CVs; range 3.1%-26.2%) were typically similar or
      better than normal baseline CTs (16.1%-19.2%). There was no evidence of
      deterioration in CTs over time, indicating at least several years test system
      stability, and Levey-Jennings plots, typically applied to IQC monitoring, could
      also be devised. This provides the first evidence of feasibility, or proof of
      concept, for IQC testing for the PFA-100 incorporating pathological test findings
      and Levey-Jennings plots. Such a concept is also potentially more broadly
      applicable to other platelet function, or whole blood or cell-based test systems.

PMID- 23152414
TI  - The diagnostic utility of brain natriuretic peptide in heart failure patients
      presenting with acute dyspnea: a meta-analysis.
AB  - Heart failure with normal ejection fraction (HFNEF) accounts for approximately
      50% of heart failure (HF) cases. To establish the utility of brain natriuretic
      peptide (BNP) in differentiating HF-related severe dyspnea from non-HF-related
      acute dyspnea, we used an estimation formula (eF) that was obtained from a series
      of three meta-regressions. We selected 60 out of 2721 case-control and follow-up
      studies that were published from 1998 to 2010. The heart failure levels (HFLs)
      were assessed using the New York Heart Association (NYHA) criteria. Random
      effects meta-regression analyses of the natural logarithm (ln) of the BNP odds
      ratio (OR) were performed on the HFLs. The ln of the median BNP values (lnmBNP)
      was meta-regressed over the laboratory method (LM). A third meta-regression was
      performed on the HFLs to account for only the lnmBNP in the homogeneous LM
      subgroups. To determine the eF, the data from the diseased and control subjects
      were combined. The Bland-Altman method was used to detect eF bias. The overall
      BNP(OR) in the subgroup with severe HF was 35. The lnmBNP analysis showed that LM
      was a significant heterogeneity factor in the meta-regression (slope -0.38; CI 
      0.59 to -0.16). The meta-regression of lnmBNP on the HFL resulted in the
      following calculation for eF: estimated HFL (eHFL)=(lnmBNP-3.157)/0.886. The
      Bland-Altman test revealed no significant difference (0.0997; 95% CI -2.84 to
      3.06) between HFL and eHFL. The severe eHFL showed a 78% accuracy. Based on the
      eF obtained from this meta-analysis, the BNP outcomes were shown to reliably
      diagnose severe dyspnea in HF and differentiate this condition from non-HF acute
      dyspnea.

PMID- 23152415
TI  - High biological variation of serum hyaluronic acid and Hepascore, a biochemical
      marker model for the prediction of liver fibrosis.
AB  - BACKGROUND: Serum hyaluronic acid and biochemical models which require hyaluronic
      acid analysis are commonly used as predictors of liver fibrosis in patients with
      chronic liver disease, however biological variation data for hyaluronic acid are
      deficient. METHODS: Four serial serum samples were obtained at weekly intervals
      from healthy volunteers and patients with chronic hepatitis B, chronic hepatitis
      C and non- alcoholic fatty liver disease (NAFLD; 20 in each group). The within
      individual week-to-week variation (CVI) and reference change values for
      hyaluronic acid, alpha2-macroglobulin and Hepascore were obtained. Hepascore is
      calculated from hyaluronic acid, alpha2-macroglobulin, bilirubin and gamma
      glutamyltransferase activity. RESULTS: Hyaluronic acid displayed large within
      individual variation, the CVI values were 62% in healthy subjects, 38% in
      hepatitis C, 37% in hepatitis B and 36% in NAFLD patients. Hepascore CVIs were
      43% in healthy subjects, 24% in hepatitis C, 28% in hepatitis B and 39% in NAFLD
      patients. alpha2-Macroglobulin was much less variable with CVIs ranging from 4.4%
      to 7.6%. Bland-Altman plots of week-to-week variations showed rates of
      significant disagreement for samples collected in any 2 successive weeks varied
      from 5% in NAFLD patients to 8.3% in healthy subjects. CONCLUSIONS: When using
      non-fasting serum samples, hyaluronic acid and to a lesser extent, the Hepascore
      model display large within-individual variations in both health and chronic liver
      disease. This information is critical for interpreting the significance of both
      single measurements and changes in serial measurements.

PMID- 23152416
TI  - Trends in clinical laboratory homocysteine testing from 1997 to 2010: the impact
      of evidence on clinical practice at a single institution.
AB  - BACKGROUND: During the past decade, several clinical trials investigating the
      potential benefits of homocysteine-lowering therapy for the secondary prevention
      of vascular events were completed and published. The objective of the study was
      to determine trends in clinical laboratory testing for homocysteine at a single
      institution over the time period from 1997 to 2010. METHODS: A single-center,
      retrospective analysis was performed at a large, academic, tertiary care medical
      center in the USA. The database was searched for clinical laboratory measurements
      of plasma or serum homocysteine between January 1, 1997 and December 31, 2010.
      Individual medical records were reviewed for a subset of 221 unique patients in
      the 10-year period from 2001 to 2010 who had homocysteine values >=20 MUmol/L.
      RESULTS: From 1997 to 2003, there was a 16-fold increase in the annual number of
      homocysteine assays performed. Testing for homocysteine declined in 2004 and
      2006, coinciding with the publication of intervention trials that failed to
      support a clinical benefit of homocysteine-lowering therapy for the secondary
      prevention of vascular events. Subgroup analysis suggested that homocysteine
      testing for the indication of suspected nutritional deficiency or
      hypercoagulability remained steady despite a decline in testing for the
      indication of cardiac risk assessment. CONCLUSIONS: The frequency of clinical
      laboratory testing for plasma or serum homocysteine changed bimodally over the
      time period from 1997 to 2010. These observations suggest that clinical practice
      was impacted by emerging evidence from association studies and intervention
      trials investigating homocysteine as a potentially treatable cardiac risk factor.

PMID- 23152417
TI  - Transferrin/log(ferritin) ratio: a self-fulfilling prophecy when iron deficiency
      is defined by serum ferritin concentration.

PMID- 23152418
TI  - Determinants of homocysteine concentrations in mother and neonatal girl pairs.

PMID- 23152419
TI  - Contributions of CCLM to advances in quality control.
AB  - Abstract The discipline of laboratory medicine is relatively young when
      considered in the context of the history of medicine itself. The history of
      quality control, within the context of laboratory medicine, also enjoys a
      relatively brief, but rich history. Laboratory quality control continues to
      evolve along with advances in automation, measurement techniques and information
      technology. Clinical Chemistry and Laboratory Medicine (CCLM) has played a key
      role in helping disseminate information about the proper use and utility of
      quality control. Publication of important advances in quality control techniques
      and dissemination of guidelines concerned with laboratory quality control has
      undoubtedly helped readers of this journal keep up to date on the most recent
      developments in this field.

PMID- 23152420
TI  - Clinical Chemistry and Laboratory Medicine: an appreciation.

PMID- 23152421
TI  - Human epididymis protein 4: the start of a post-ROMAn era?

PMID- 23152422
TI  - Aqueous humor glycation marker and plasma homocysteine in macular degeneration.
AB  - BACKGROUND: We investigated concentrations of total homocysteine (tHcy) in
      elderly people without and those with age-related macular degeneration (AMD). In
      addition, we tested the association between plasma tHcy and one glycation marker
      in aqueous humor. METHODS: People with cataract only (n=48), patients with dry
      AMD (n=38) and those with wet AMD (n=31) were studied. Blood concentrations of
      tHcy, and methylation and vitamin markers were measured in 116 blood samples. The
      concentrations of the extracellular soluble receptor for advanced glycated end
      products (esRAGE) were measured in 77 aqueous humor samples. RESULTS: Mean
      aqueous humor concentration of esRAGE and that of plasma tHcy did not differ
      significantly between the groups. Arterial hypertension but not eye disease
      explained the tHcy elevation in plasma in this study. In the cataract group, a
      significant negative correlation was found between plasma tHcy and that of esRAGE
      in aqueous humor (r=-0.483, p=0.006). In patients with dry AMD, the concentration
      of esRAGE in aqueous humor correlated negatively to tHcy and positively to serum
      folate. CONCLUSIONS: Plasma tHcy levels were positively associated with
      hypertension, but not with AMD in this study. Higher esRAGE in aqueous humor was
      related to higher folate and lower tHcy in blood. Following studies may assess
      whether B-vitamins can protect against age-related ocular diseases by reducing
      glycation.

PMID- 23152423
TI  - Metrological traceability - a concept for standardization in laboratory medicine.
AB  - The concept of measurement traceability provides the most important strategy in
      achieving standardization in laboratory medicine aimed at equivalent measurement
      results regardless of the principle of measurement, the method, the actual
      measurement procedure (test kit) and the laboratory where analyses are carried
      out.

PMID- 23152424
TI  - Harmonization of immunoassays to the all-procedure trimmed mean - proof of
      concept by use of data from the insulin standardization project.

PMID- 23152425
TI  - ExactDAS: an exact test procedure for the detection of differential alternative
      splicing in microarray experiments.
AB  - The aim of this paper is to propose a test procedure for the detection of
      differential alternative splicing across conditions for tiling array or exon chip
      data. While developed in a mixed model framework, the test procedure is exact
      (avoiding computational burden) and applicable to a large variety of contrasts,
      including several previously published ones. A simulation study is presented to
      evaluate the robustness and performance of the method. It is found to have a good
      detection power of genes under differential alternative splicing, even for five
      biological replicates and four probes per exon. The methodology also enables the
      comparison of various experimental designs through exact power curves. This is
      illustrated with the comparison of paired and unpaired experiments. The test
      procedure was applied to two publicly available cancer data sets based on exon
      arrays, and showed promising results.

PMID- 23152426
TI  - Large-scale parentage inference with SNPs: an efficient algorithm for statistical
      confidence of parent pair allocations.
AB  - Advances in genotyping that allow tens of thousands of individuals to be
      genotyped at a moderate number of single nucleotide polymorphisms (SNPs) permit
      parentage inference to be pursued on a very large scale. The intergenerational
      tagging this capacity allows is revolutionizing the management of cultured
      organisms (cows, salmon, etc.) and is poised to do the same for scientific
      studies of natural populations. Currently, however, there are no likelihood-based
      methods of parentage inference which are implemented in a manner that allows them
      to quickly handle a very large number of potential parents or parent pairs. Here
      we introduce an efficient likelihood-based method applicable to the specialized
      case of cultured organisms in which both parents can be reliably sampled. We
      develop a Markov chain representation for the cumulative number of Mendelian
      incompatibilities between an offspring and its putative parents and we exploit it
      to develop a fast algorithm for simulation-based estimates of statistical
      confidence in SNP-based assignments of offspring to pairs of parents. The method
      is implemented in the freely available software SNPPIT. We describe the method in
      detail, then assess its performance in a large simulation study using known
      allele frequencies at 96 SNPs from ten hatchery salmon populations. The
      simulations verify that the method is fast and accurate and that 96 well-chosen
      SNPs can provide sufficient power to identify the correct pair of parents from
      amongst millions of candidate pairs.

PMID- 23152427
TI  - Toward the development of a nursing practice for older persons with acute
      confusional state (ACS).
AB  - Surgery unit nurses often deal with older people in an acute confusional state
      (ACS). To care for them, nurses must resort to different patterns of knowing,
      including empirical, esthetic, ethical, personal and emancipatory. According to
      Chinn and Kramer (2008), it is by consciously and deliberately asking themselves
      critical questions about specific clinical situations that nurses can enhance
      their knowledge and improve practice. In this regard, narrative pedagogy
      developed by Diekelmann (2001), which encourages sharing lived experiences and
      seeking other possibilities for the future, seems a well suited approach. This
      article presents the theoretical bases of narrative pedagogy and the grounds for
      an intervention inspired by this approach and intended for nurses who must care
      for hospitalized older people in an ACS. This innovative pedagogical
      intervention, which encourages nurses to participate actively in their learning,
      is consistent with recent empirical works on continuing education of health
      professionals.

PMID- 23152428
TI  - Effect of Smilax zeylanica roots and rhizomes in paracetamol induced
      hepatotoxicity.
AB  - CONTEXT: Smilax zeylanica L.(Smilacaceae) is a climbing shrub with woody prickly
      stems. OBJECTIVE: This study evaluated the hepatoprotective effect of S.
      zeylanica against paracetamol induced hepatotoxicity in Wistar rats. MATERIALS
      AND METHODS: The protective effects of the methanol extract (200 and 400 mg/kg)
      of root and rhizome of S. zeylanica were studied on paracetamol induced (1 g/kg)
      hepatic damage in Wistar rats by estimating the serum levels of AST, ALT,
      alkaline phosphatase (ALP), total proteins, total bilirubin and albumin. Sections
      of liver were observed for histopathological changes in liver architecture.
      RESULTS: Rats were protected from the hepatotoxic action of paracetamol as
      evidenced by the significant reduction in the elevated serum levels of ALT
      (P<0.001), AST (P< 0.01, P< 0.001), ALP (P<0.05, P< 0.001), total bilirubin (P<
      0.05) and an increased level of total protein (P< 0.05) and albumin (P< 0.05,
      P<0.01) with a significant reduction in liver weight (P<0.001), when compared
      with the paracetamol control. Silymarin (100 mg/kg) was used as the standard.
      DISCUSSION AND CONCLUSION: The biochemical observations were supplemented by the
      histopathological studies on the liver sections of different groups. The methanol
      extract of S. zeylanica was found to alter the damage caused to hepatocytes by
      paracetamol and prevent the leakage of vital serum markers, which confirmed the
      hepatoprotective effect of this plant.

PMID- 23152429
TI  - Using role substitution to address the health workforce shortage and to
      facilitate integration?
AB  - The health workforce is perceived to be in short supply in most developed and
      developing countries. There are concerns that this could result in reduced
      coverage of health services and the delivery of suboptimal care. Strategies to
      address the health workforce shortage have focussed predominantly on recruitment
      and training, with relatively little regard to the equally important issue of
      retention. One approach that may improve job satisfaction, opportunities for
      specialisation and the workload of health workers, and thus, improve retention
      and more importantly, patient outcomes, is role substitution. Many complementary
      and alternative medicine (CAM) practitioners appear to be well placed in terms of
      educational preparation to substitute (either horizontally or vertically) a
      number of roles traditionally performed by conventional health disciplines. As
      well as the potential benefits to the health workforce and the quality of patient
      care, role substitution could provide an important first step toward integrating
      CAM practitioners into mainstream health care settings.

PMID- 23152430
TI  - The antidiabetic activities of the methanolic root bark extract of Afzelia
      africana in alloxan-induced diabetic mice.
AB  - The methanolic root bark extract of Afzelia africana was tested for antidiabetic
      activities in-vivo. The acute toxicity of the extract was tested in mice and the
      result showed that the extract has low toxicity. Investigation on the
      phytochemical constituents of the plant extract revealed the presence of
      flavonoids, tannins, alkaloids, steroids and saponins. The plant extract was
      tested for antidiabetic activities in alloxan - induced diabetic mice at doses of
      62.5 mg/kg, 125 mg/kg, 250 mg/kg, 500 mg/kg and 1000 mg/kg over a period of 6
      hours. The activity was found to be both dose and time dependent. Optimum
      activity was noted at the dose of 250 mg/kg and 6 hours post treatment. Distilled
      water (10 ml/kg) and glibenclamide (2 mg/kg) were used as negative and positive
      controls respectively. The extract showed antidiabetic activity which did not
      differ significantly (p > 0.05) from glibenclamide. Column and thin layer
      chromatography revealed the presence of 5 fractions in the plant extract out of
      which fraction 3 was found to be active.

PMID- 23152431
TI  - A comparative study of parametric and nonparametric estimates of the attributable
      fraction for a semi-continuous exposure.
AB  - The attributable fraction of a disease due to an exposure is the fraction of
      disease cases in a population that can be attributed to that exposure. We
      consider the attributable fraction for a semi-continuous exposure, that is an
      exposure for which a clump of people have zero exposure and the rest of the
      people have a continuously distributed positive exposure. Estimation of the
      attributable fraction involves estimating the conditional probability of having
      the disease given the exposure. Three main approaches to estimating the
      probability function are (1) a classical method based on sample averages; (2)
      parametric regression methods such as logistic regression models and power
      models; and (3) nonparametric regression methods including local linear smoothing
      and isotonic regression. We compare performance of these methods in estimating
      the attributable fraction for a semi-continuous exposure in a simulation study
      and in an example.

PMID- 23152432
TI  - Partial identification arising from nondifferential exposure misclassification:
      how informative are data on the unlikely, maybe, and likely exposed?
AB  - There is quite an extensive literature on the deleterious impact of exposure
      misclassification when inferring exposure-disease associations, and on
      statistical methods to mitigate this impact. Virtually all of this work, however,
      presumes a common number of states for the true exposure status and the
      classified exposure status. In the simplest situation, for instance, both the
      true status and the classified status are binary. The present work diverges from
      the norm, in considering classification into three states when the actual
      exposure status is simply binary. Intuitively, the classification states might be
      labeled as 'unlikely exposed,' 'maybe exposed,' and 'likely exposed.' While this
      situation has been discussed informally in the epidemiological literature, we
      provide some theory concerning what can be learned about the exposure-disease
      relationship, under various assumptions about the classification scheme. We focus
      on the challenging situation whereby no validation data is available from which
      to infer classification probabilities, but some prior assertions about these
      probabilities might be justified.

PMID- 23152433
TI  - Projecting cancer incidence using age-period-cohort models incorporating
      restricted cubic splines.
AB  - Age-period-cohort models provide a useful method for modeling incidence and
      mortality rates. There is great interest in estimating the rates of disease at
      given future time-points in order that plans can be made for the provision of the
      required future services. In the setting of using age-period-cohort models
      incorporating restricted cubic splines, a new technique for projecting incidence
      is proposed. The new technique projects the period and cohort terms linearly from
      10 years within the range of the available data in order to give projections that
      are based on recent trends. The method is validated via a comparison with
      existing methods in the setting of Finnish cancer registry data. The reasons for
      the improvements seen for the newly proposed method are twofold. Firstly,
      improvements are seen due to the finer splitting of the timescale to give a more
      continuous estimate of the incidence rate. Secondly, the new method uses more
      recent trends to dictate the future projections than previously proposed methods.

PMID- 23152434
TI  - Targeted maximum likelihood estimation for prediction calibration.
AB  - Estimators of the conditional expectation, i.e., prediction, function involve a
      global bias-variance trade off. In some cases, an estimator that yields unbiased
      estimates of the conditional expectation for a particular partitioning of the
      data may be desirable. Such estimators are calibrated with respect to the
      partitioning. We identify the conditional expectation given a particular
      partitioning as a smooth parameter of the distribution of the data, where the
      partitioning may be defined on the covariate space or on the prediction space of
      the estimator. We propose a targeted maximum likelihood estimation (TMLE)
      procedure that updates an initial prediction estimator such that the updated
      estimator yields an unbiased and efficient estimator of this smooth parameter in
      the nonparametric statistical model. When the partitioning is defined on the
      prediction space of the estimator, our TMLE involves enforcing an implicit
      constraint on the estimator itself. We show that our resulting estimator of the
      smooth parameter is equal to the empirical estimator, which is also known to be
      unbiased and efficient in the nonparametric statistical model. We derive the TMLE
      for single time-point prediction and also time-dependent prediction in a counting
      process framework.

PMID- 23152435
TI  - The intrathoracic vacuum-assisted closure device in case of post-pneumonectomy
      empyema.

PMID- 23152436
TI  - Dynamic trends in cardiac surgery: why the logistic EuroSCORE is no longer
      suitable for contemporary cardiac surgery and implications for future risk
      models.
AB  - OBJECTIVES: Progressive loss of calibration of the original EuroSCORE models has
      necessitated the introduction of the EuroSCORE II model. Poor model calibration
      has important implications for clinical decision-making and risk adjustment of
      governance analyses. The objective of this study was to explore the reasons for
      the calibration drift of the logistic EuroSCORE. METHODS: Data from the Society
      for Cardiothoracic Surgery in Great Britain and Ireland database were analysed
      for procedures performed at all National Health Service and some private
      hospitals in England and Wales between April 2001 and March 2011. The primary
      outcome was in-hospital mortality. EuroSCORE risk factors, overall model
      calibration and discrimination were assessed over time. RESULTS: A total of 317
      292 procedures were included. Over the study period, mean age at surgery
      increased from 64.6 to 67.2 years. The proportion of procedures that were
      isolated coronary artery bypass grafts decreased from 67.5 to 51.2%. In-hospital
      mortality fell from 4.1 to 2.8%, but the mean logistic EuroSCORE increased from
      5.6 to 7.6%. The logistic EuroSCORE remained a good discriminant throughout the
      study period (area under the receiver-operating characteristic curve between 0.79
      and 0.85), but calibration (observed-to-expected mortality ratio) fell from 0.76
      to 0.37. Inadequate adjustment for decreasing baseline risk affected calibration
      considerably. DISCUSSIONS: Patient risk factors and case-mix in adult cardiac
      surgery change dynamically over time. Models like the EuroSCORE that are
      developed using a 'snapshot' of data in time do not account for this and can
      subsequently lose calibration. It is therefore important to regularly revalidate
      clinical prediction models.

PMID- 23152437
TI  - Small interfering RNA-mediated suppression of serum response factor, E2-promotor
      binding factor and survivin in non-small cell lung cancer cell lines by non-viral
      transfection.
AB  - OBJECTIVES: Serum response factor (SRF), E2F1 and survivin are well-known factors
      involved in a multitude of cancer-related regulation processes. However, to date,
      no suitable means has been found to apply their potential in the therapy of non
      small cell lung cancer (NSCLC). This study deals with questions of small
      interfering ribonucleic acid (siRNA) transfection efficiency by a non-viral
      transfection of NSCLC cell-lines and the power of siRNA to transiently influence
      cell division by specific silencing. METHODS: Different NSCLC cell lines were
      cultured under standard conditions and transfected, with specific siRNA targeting
      SRF, E2F1 and survivin in a non-viral manner. Cells treated with non-specific
      siRNA (SCR-siRNA) served as controls. Quantitative real-time polymerase chain
      reaction (qRT-PCR) was performed for messenger RNA (mRNA) expression levels.
      Additionally, transfection efficiency was evaluated by flow cytometry. The
      analysis of cell proliferation was determined with a CASY cell counter 3 days
      after transfection with SRF or SCR-siRNA. RESULTS: Transfection of the NSCLC cell
      lines with specific siRNAs against SRF, E2F1 and survivin resulted in a very
      considerable reduction of the intracellular mRNA concentration. CASY confirmation
      of cell viability demonstrated an excellent survival of the cell lines treated
      with non-specific siRNA, in contrast to with application of specific siRNA.
      CONCLUSIONS: This study reports a reliable transfectability of NSCLC-cell lines
      by siRNA, initially in a non-viral manner, and a reproducible knockdown of the
      focussed targets, consequently leading to the death of the tumour cells. This
      constitutes a strong candidate for a new assessment strategy in the therapy of
      non-small cell lung cancer.

PMID- 23152438
TI  - Magnetic resonance imaging of CNS in 15,043 children with GH deficiency in KIGS
      (Pfizer International Growth Database).
AB  - OBJECTIVES: Neuroimaging has become an essential part of the diagnostic process
      in children with GH deficiency (GHD). The aim of the study was to document the
      frequency of neuroanatomical abnormalities in a very large cohort of children
      with GHD and to relate these findings to patient clinical characteristics. DESIGN
      AND METHODS: Results of magnetic resonance imaging (MRI) were reported in 15,043
      of 43,725 children with non-acquired GHD (idiopathic, neurosecretory dysfunction
      (NSD) and known congenital cause) who were enrolled in KIGS (Pfizer International
      Growth Database) between 1987 and 2011. Clinical characteristics of patients
      before GH treatment with normal MRI (idiopathic GHD (IGHD) and NSD) were compared
      with those of patients with abnormal pituitaries (hypoplasia, empty sella (ES),
      HME (hypoplastic anterior pituitary, missing pituitary stalk and ectopic
      posterior pituitary)). RESULTS: Abnormal MRIs were found in 4032 (26.8%)
      children, within which ES (N=1178 (7.8%)) and HME (N=1019 (6.8%)) were the most
      frequent findings. In 2361 children diagnosed as IGHD or NSD before MRI
      examination, anatomical abnormalities ((pituitary hypoplasia: n=974); (HME:
      n=459)) were documented. Patients with anatomical abnormalities had more severe
      characteristics of GHD: normal MRI < pituitary hypoplasia < ES < HME.
      CONCLUSIONS: GHD is associated with a great variety of neuroanatomical
      abnormalities as identified by MRI. The investigation and evaluation of MRI need
      to be conducted in a structured mode. There is an association between anatomical
      and functional abnormalities of the pituitary.

PMID- 23152439
TI  - Hungry bone syndrome: still a challenge in the post-operative management of
      primary hyperparathyroidism: a systematic review of the literature.
AB  - Hungry bone syndrome (HBS) refers to the rapid, profound, and prolonged
      hypocalcaemia associated with hypophosphataemia and hypomagnesaemia, and is
      exacerbated by suppressed parathyroid hormone (PTH) levels, which follows
      parathyroidectomy in patients with severe primary hyperparathyroidism (PHPT) and
      preoperative high bone turnover. It is a relatively uncommon, but serious adverse
      effect of parathyroidectomy. We conducted a literature search of all available
      studies reporting a 'hungry bone syndrome' in patients who had a
      parathyroidectomy for PHPT, to identify patients at risk and address the pitfalls
      in their management. The severe hypocalcaemia is believed to be due to increased
      influx of calcium into bone, due to the sudden removal of the effect of high
      circulating levels of PTH on osteoclastic resorption, leading to a decrease in
      the activation frequency of new remodelling sites and to a decrease in
      remodelling space, although there is no good documentation for this. Various risk
      factors have been suggested for the development of HBS, including older age,
      weight/volume of the resected parathyroid glands, radiological evidence of bone
      disease and vitamin D deficiency. The syndrome is reported in 25-90% of patients
      with radiological evidence of hyperparathyroid bone disease vs only 0-6% of
      patients without skeletal involvement. There is insufficient data-based evidence
      on the best means to treat, minimise or prevent this severe complication of
      parathyroidectomy. Treatment is aimed at replenishing the severe calcium deficit
      by using high doses of calcium supplemented by high doses of active metabolites
      of vitamin D. Adequate correction of magnesium deficiency and normalisation of
      bone turnover are required for resolution of the hypocalcaemia which may last for
      a number of months after successful surgery. Preoperative treatment with
      bisphosphonates has been suggested to reduce post-operative hypocalcaemia, but
      there are to date no prospective studies addressing this issue.

PMID- 23152440
TI  - GH therapy in adult GH deficiency: a review of treatment schedules and the
      evidence for low starting doses.
AB  - Recombinant human GH has been licensed for use in adult patients with GH
      deficiency (GHD) for over 15 years. Early weight- and surface area-based dosing
      regimens were effective but resulted in supraphysiological levels of IGF1 and
      increased incidence of side effects. Current practice has moved towards
      individualised regimens, starting with low GH doses and gradually titrating the
      dose according to the level of serum IGF1 to achieve an optimal dose. Here we
      present the evidence supporting the dosing recommendations of current guidelines
      and consider factors affecting dose responsiveness and parameters of treatment
      response. The published data discussed here lend support for the use of low GH
      dosing regimens in adult GHD. The range of doses defined as 'low dose' in the
      studies discussed here (~1-4  mg/week) is in accordance with those recommended in
      current guidelines and encompasses the dose range recommended by product labels.

PMID- 23152441
TI  - Coronary microvascular function, myocardial metabolism, and energetics in
      hypertrophic cardiomyopathy: insights from positron emission tomography.
AB  - Hypertrophic cardiomyopathy (HCM) is a major cause of sudden cardiac death in
      adolescence, and may lead to heart failure at any age. However, significant
      heterogeneity in the clinical course and phenotypic expression exists. Next to
      left ventricular hypertrophy, an impaired myocardial blood flow (MBF) during
      stress and inefficient cardiac metabolism are other characteristics of HCM.
      Studies using positron emission tomography (PET) have led to an enhanced
      understanding of the role that myocardial ischaemia and impaired energetics play
      in the clinical course of HCM. The blunted vasodilator reserve in the absence of
      an epicardial coronary stenosis is the result of microvascular dysfunction.
      Microvascular dysfunction, in turn, represents a predisposing factor for
      myocardial ischaemia, which may lead to cardiac dysfunction and fibrosis.
      Correspondingly, the severity of microvascular dysfunction has been shown to
      serve as a major predictor of mortality. Myocardial energetics in HCM has been
      studied with similar interest as mounting evidence suggests that mechano
      energetic uncoupling may play a central role in its pathogenesis. Although
      prognostic data related to an impaired energetic state in HCM are lacking, it may
      hold prognostic relevance. Consequently, enhancing perfusion and restoring
      energetics have gained considerable attention as potential strategies to alter
      the natural course of HCM. In this regard, myocardial perfusion and metabolic
      imaging serves as a valuable tool to monitor the effects of therapeutic
      interventions on the pathophysiology of HCM.

PMID- 23152442
TI  - IGF1 dependence of dietary energy balance effects on murine Met1 mammary tumor
      progression, epithelial-to-mesenchymal transition, and chemokine expression.
AB  - Luminal breast tumors with little or no estrogen receptor alpha expression confer
      poor prognosis. Using the Met1 murine model of luminal breast cancer, we
      characterized the IGF1-dependency of diet-induced obesity (DIO) and calorie
      restriction (CR) effects on tumor growth, growth factor signaling, epithelial-to
      mesenchymal transition (EMT), and chemokine expression. Liver-specific IGF1
      deficient (LID) and littermate control (LC) mice were administered control, DIO,
      or 30% CR diets for 3 months before orthotopic injection of Met1 cells. Tumors
      grew for 1 month and then were assessed for Akt pathway activation and mRNA
      expression of chemokine and EMT constituents. LID mice, regardless of diet,
      displayed reduced Met1 tumor growth and downregulated Akt, EMT, and chemokine
      pathways. CR, relative to control, reduced serum IGF1 and Met1 tumor growth in LC
      (but not LID) mice. DIO, relative to control, increased Met1 tumor growth and
      chemokine expression in LID mice, and had no effect on serum IGF1 or pAkt or
      cyclin D1 expression in either genotype. Thus, circulating IGF1 (in association
      with Akt, EMT, and chemokines) regulated Met1 tumor growth. While the anticancer
      effects of CR were largely IGF1-dependent, the procancer effects of DIO
      manifested only when circulating IGF1 levels were low. Thus, in a murine model of
      luminal breast cancer, IGF1 and its downstream signaling pathway, EMT, and
      chemokines present possible mechanistic regulatory targets. Transplanted MMTV1
      Wnt1 mammary tumor growth was also reduced in LID mice, relative to LC mice,
      suggesting that the IGF1 effects on mammary tumor growth are not limited to Met1
      tumors.

PMID- 23152445
TI  - Retroaortic abscess: an unusual complication of a retained epicardial pacing
      wire.
AB  - Infectious complications related to retained temporary epicardial pacing wires
      are rare. We report a case of a focal retroaortic abscess in association with
      retained pacing wires that became manifest 3 years after surgery for tricuspid
      valve endocarditis.

PMID- 23152444
TI  - A novel genetic variant in the transcription factor Islet-1 exerts gain of
      function on myocyte enhancer factor 2C promoter activity.
AB  - AIMS: The transcription factor Islet-1 (ISL1) is a marker of cardiovascular
      progenitors and is essential for mammalian cardiogenesis. An ISL1 haplotype has
      recently been associated with congenital heart disease. In this study we
      evaluated whether ISL1 variants are associated with hypertrophic (HCM), dilated
      (DCM), arrhythmogenic right ventricular cardiomyopathy (ARVC), or with Emery
      Dreifuss muscular dystrophy (EDMD). METHODS AND RESULTS: The six exon and intron
      boundaries of ISL1 were screened for genetic variants in a cohort of 454 index
      cases. Eleven exonic variants were identified in HCM, DCM, ARVC, and/or EDMD. Out
      of the five novel variants, two are located in the 5'-untranslated region, two
      are silent (p.Arg171Arg and p.Asn189Asn), and one is a missense (p.Asn252Ser).
      The latter was identified in the homozygous state in one DCM patient, and in the
      heterozygous state in 11 relatives, who did not present with DCM but often with
      cardiovascular features. This variant was found in one HCM patient also carrying
      a MYH7 mutation and in 3/96 North-African Caucasian control individuals, but was
      absent in 138 European Caucasian control individuals. We investigated the effect
      of the ISL1 wild type and p.Asn252Ser mutant on myocyte enhancer factor 2C
      (Mef2c) promoter activity, an established ISL1 target. Mef2c promoter activity
      was ~4-fold higher in the presence of wild-type and ~6-fold higher in the
      presence of mutant ISL1 in both HEK and CHO cells. CONCLUSION: This study
      describes a new gain-of-function p.Asn252Ser variant in the human ISL1 gene,
      which could potentially lead to greater activation of downstream targets involved
      in cardiac development, dilation, and hypertrophy.

PMID- 23152446
TI  - Whole-genome microRNA screening identifies let-7 and mir-18 as regulators of germ
      layer formation during early embryogenesis.
AB  - Tight control over the segregation of endoderm, mesoderm, and ectoderm is
      essential for normal embryonic development of all species, yet how neighboring
      embryonic blastomeres can contribute to different germ layers has never been
      fully explained. We postulated that microRNAs, which fine-tune many biological
      processes, might modulate the response of embryonic blastomeres to growth factors
      and other signals that govern germ layer fate. A systematic screen of a whole
      genome microRNA library revealed that the let-7 and miR-18 families increase
      mesoderm at the expense of endoderm in mouse embryonic stem cells. Both families
      are expressed in ectoderm and mesoderm, but not endoderm, as these tissues become
      distinct during mouse and frog embryogenesis. Blocking let-7 function in vivo
      dramatically affected cell fate, diverting presumptive mesoderm and ectoderm into
      endoderm. siRNA knockdown of computationally predicted targets followed by
      mutational analyses revealed that let-7 and miR-18 down-regulate Acvr1b and
      Smad2, respectively, to attenuate Nodal responsiveness and bias blastomeres to
      ectoderm and mesoderm fates. These findings suggest a crucial role for the let-7
      and miR-18 families in germ layer specification and reveal a remarkable
      conservation of function from amphibians to mammals.

PMID- 23152447
TI  - The role of PR-Set7 in replication licensing depends on Suv4-20h.
AB  - PR-Set7 is the sole monomethyltransferase responsible for H4K20 monomethylation
      (H4K20me1) that is the substrate for further methylation by Suv4-20h1/h2. PR-Set7
      is required for proper cell cycle progression and is subject to degradation by
      the CRL4(Cdt2) ubiquitin ligase complex as a function of the cell cycle and DNA
      damage. This report demonstrates that PR-Set7 is an important downstream effector
      of CRL4(Cdt2) function during origin of DNA replication licensing, dependent on
      Suv4-20h1/2 activity. Aberrant rereplication correlates with decreased levels of
      H4K20me1 and increased levels of H4K20 trimethylation (H4K20me3). Expression of a
      degradation-resistant PR-Set7 mutant in the mouse embryo that is normally devoid
      of Suv4-20 does not compromise development or cell cycle progression unless Suv4
      20h is coexpressed. PR-Set7 targeting to an artificial locus results in
      recruitment of the origin recognition complex (ORC) in a manner dependent on Suv4
      20h and H4K20me3. Consistent with this, H4K20 methylation status plays a direct
      role in recruiting ORC through the binding properties of ORC1 and ORCA/LRWD1.
      Thus, coordinating the status of H4K20 methylation is pivotal for the proper
      selection of DNA replication origins in higher eukaryotes.

PMID- 23152448
TI  - Pediatric glioma-associated KIAA1549:BRAF expression regulates neuroglial cell
      growth in a cell type-specific and mTOR-dependent manner.
AB  - Tandem duplications involving the BRAF kinase gene have recently been identified
      as the most frequent genetic alteration in sporadic pediatric glioma, creating a
      novel fusion protein (f-BRAF) with increased BRAF activity. To define the role of
      f-BRAF in gliomagenesis, we demonstrate that f-BRAF regulates neural stem cell
      (NSC), but not astrocyte, proliferation and is sufficient to induce glioma-like
      lesions in mice. Moreover, f-BRAF-driven NSC proliferation results from
      tuberin/Rheb-mediated mammalian target of rapamycin (mTOR) hyperactivation,
      leading to S6-kinase-dependent degradation of p27. Collectively, these results
      establish mTOR pathway activation as a key growth regulatory mechanism common to
      both sporadic and familial low-grade gliomas in children.

PMID- 23152449
TI  - Correlated alterations in genome organization, histone methylation, and DNA-lamin
      A/C interactions in Hutchinson-Gilford progeria syndrome.
AB  - Hutchinson-Gilford progeria syndrome (HGPS) is a premature aging disease that is
      frequently caused by a de novo point mutation at position 1824 in LMNA. This
      mutation activates a cryptic splice donor site in exon 11, and leads to an in
      frame deletion within the prelamin A mRNA and the production of a dominant
      negative lamin A protein, known as progerin. Here we show that primary HGPS skin
      fibroblasts experience genome-wide correlated alterations in patterns of H3K27me3
      deposition, DNA-lamin A/C associations, and, at late passages, genome-wide loss
      of spatial compartmentalization of active and inactive chromatin domains. We
      further demonstrate that the H3K27me3 changes associate with gene expression
      alterations in HGPS cells. Our results support a model that the accumulation of
      progerin in the nuclear lamina leads to altered H3K27me3 marks in
      heterochromatin, possibly through the down-regulation of EZH2, and disrupts
      heterochromatin-lamina interactions. These changes may result in transcriptional
      misregulation and eventually trigger the global loss of spatial chromatin
      compartmentalization in late passage HGPS fibroblasts.

PMID- 23152450
TI  - Obligate ligation-gated recombination (ObLiGaRe): custom-designed nuclease
      mediated targeted integration through nonhomologous end joining.
AB  - Custom-designed nucleases (CDNs) greatly facilitate genetic engineering by
      generating a targeted DNA double-strand break (DSB) in the genome. Once a DSB is
      created, specific modifications can be introduced around the breakage site during
      its repair by two major DNA damage repair (DDR) mechanisms: the dominant but
      error-prone nonhomologous end joining (NHEJ) pathway, and the less-frequent but
      precise homologous recombination (HR) pathway. Here we describe ObLiGaRe, a new
      method for site-specific gene insertions that uses the efficient NHEJ pathway and
      acts independently of HR. This method is applicable with both zinc finger
      nucleases (ZFNs) and Tale nucleases (TALENs), and has enabled us to insert a 15
      kb inducible gene expression cassette at a defined locus in human cell lines. In
      addition, our experiments have revealed the previously underestimated error-free
      nature of NHEJ and provided new tools to further characterize this pathway under
      physiological and pathological conditions.

PMID- 23152451
TI  - Reflecting on Dr. Ian McWhinney.

PMID- 23152452
TI  - Reduction of shoulder dislocation: are communication and adequate relaxation more
      important than technique?

PMID- 23152453
TI  - Testing 1, 2, 3: is overtesting undermining patient and system health?

PMID- 23152454
TI  - From paternalism to benevolent coaching: new model of care.

PMID- 23152455
TI  - Effective detection and management of low-velocity Lisfranc injuries in the
      emergency setting: principles for a subtle and commonly missed entity.
AB  - OBJECTIVE: To improve the ability of primary care physicians to recognize the
      mechanisms and common presentations of low-velocity Lisfranc injuries (LFIs) and
      to impart an improved understanding of the role of imaging and principles of
      primary care in low-velocity LFIs. SOURCES OF INFORMATION: A MEDLINE literature
      review was performed and the results were summarized, reviewing anatomy and
      mechanisms, clinical and imaging-based diagnoses, and management principles in
      the primary care setting. MAIN MESSAGE: Low-velocity LFIs result from various
      mechanisms and can have very subtle findings on clinical examination and imaging.
      A high degree of suspicion and caution are warranted when managing this type of
      injury. CONCLUSION: Although potentially devastating if missed, if a few
      treatment principles for low-velocity LFIs are applied from the initial
      presentation onward, outcomes from this injury can be optimized.

PMID- 23152456
TI  - Primary care of people with spinal cord injury: scoping review.
AB  - OBJECTIVE: To perform a scoping review of the empirical evidence between 1980 and
      2009 regarding primary care for adults with spinal cord injury (SCI). DATA
      SOURCES: Peer-reviewed journals were searched from 1980 to 2009 using CINAHL,
      PubMed-MEDLINE, EMBASE, PsycINFO, Social Sciences Abstracts, and Social Work
      Abstracts. STUDY SELECTION: The key word-driven electronic search identified 42
      articles on primary care and SCI. Inclusion criteria narrowed the set to 21
      articles that were published in English, that had a sample size of greater than
      3, and that offered empirical analysis. SYNTHESIS: Approximately 90% of people
      with SCI identify family physicians as their regular doctors; 63% have SCI
      specialists. People with long-term SCI develop complex rubrics for navigating
      their personal health care systems. There is conflicting evidence about the
      effectiveness of outreach programs for maintaining health and preventing
      complications following SCI. Regular follow-up by specialized teams and annual
      comprehensive health examination are supported by the evidence. The research
      shows a high level of consistency in identifying the most common issues raised by
      people with SCI in primary care, most of which are related to disability
      specifically, secondary complications such as bowel or bladder dysfunction and
      pain. There is also good evidence that many general health issues require
      attention in this population, such as bone density problems, depression, and
      sexual and reproductive health issues. There is level 4 and 5 evidence for unmet
      health needs among individuals living with SCI in the community. Despite patients
      with SCI being high users of primary care and health services in general, the
      evidence suggests that the information needs of these patients in particular are
      poorly met. CONCLUSION: A robust system of primary care is the best assurance of
      good health outcomes and reasonable health service use for people with SCI,
      including annual comprehensive examination, appropriate specialist use, and
      attention to accessibility and unmet needs.

PMID- 23152457
TI  - Maternal cocaine use during breastfeeding.
AB  - QUESTION: In my practice several patients have struggled with cocaine abuse
      during their pregnancies. One woman, now postpartum, wants to breastfeed her
      infant. Despite being abstinent for the final few months of her pregnancy, I am
      concerned about the potential adverse effects on her child if she happens to
      relapse. What is the current evidence about the risks of cocaine exposure during
      breastfeeding? ANSWER: Given the substantial benefits of breastfeeding for infant
      health and development, there is no reason for mothers who previously abused
      cocaine to avoid breastfeeding. It is important for the health care team to
      counsel patients both on the serious potential risks of cocaine exposure for
      babies and on the benefits of breastfeeding, to allow for an informed choice.
      Additionally, attempts should be made to estimate maternal commitment to
      breastfeeding and discontinuation of cocaine use, and to offer addiction
      counseling to mitigate the potential risks of infant cocaine exposure. It is
      paramount to minimize the risk to the infant, which would certainly include
      mothers ceasing use of cocaine while breastfeeding. For mothers who elect to
      breastfeed and use cocaine intermittently, breastfeeding should be delayed
      sufficiently after cocaine use to allow for drug elimination (approximately 24
      hours).

PMID- 23152458
TI  - Acute otitis externa in children.
AB  - QUESTION: In the summer months I see many children with uncomplicated acute
      otitis externa (AOE). I am aware of the multiple ototopical preparations. Which
      is the best first-line agent to treat AOE, and is there a role for an oral
      antibiotic? ANSWER: There are no specific Canadian guidelines for the management
      of AOE. However, current American guidelines promote initial ototopical therapy
      without systemic antibiotics for uncomplicated AOE; suggest there is little
      difference between the various ototopical preparations; and recommend the choice
      of treatment be based on the specific clinical situation. In practice, this often
      results in prescribing an antibiotic-steroid formulation for 7 to 10 days. This
      ototopical treatment option is supported by a recent Cochrane review that has
      documented the superiority of an antibiotic-steroid combination when compared
      with placebo or acetic acid in providing clinical resolution of AOE.

PMID- 23152459
TI  - Omega-3 for patients with cardiovascular disease.

PMID- 23152460
TI  - Nutrient effects on stress reaction to bone.

PMID- 23152461
TI  - Unusual case of recurrent falls: myasthenia gravis in an elderly patient.

PMID- 23152462
TI  - Dermacase. Can you identify this condition? Lichen amyloidosis.

PMID- 23152463
TI  - Physical activity after stroke and spinal cord injury: evidence-based
      recommendations on clearance for physical activity and exercise.

PMID- 23152464
TI  - Breast cyst aspiration.

PMID- 23152465
TI  - Family physicians providing regular care to residents in Ontario long-term care
      homes: characteristics and practice patterns.
AB  - OBJECTIVE: To describe the characteristics and practice patterns of family
      physicians who regularly treat long-term care (LTC) residents in order to inform
      quality improvement strategies. DESIGN: Cross-sectional study involving a 2005
      province-wide census of LTC residents' charts linked to additional health care
      administrative databases. SETTING: All LTC homes in Ontario. PARTICIPANTS:
      Residents aged 66 years and older (n = 50375) and the family physicians (n =
      1190) most responsible for their care. MAIN OUTCOME MEASURES: Distribution of LTC
      residents across family physicians, and physician demographic characteristics and
      practice patterns. RESULTS: The distribution of residents across physicians was
      highly skewed (median 27 residents, mean 42.5 residents). The care of 90.4% of
      residents was accounted for by 628 (52.8%) identified physicians. Family
      physicians practising in LTC facilities were more likely to be older (mean age
      52.4 years vs 48.2 years, P < .001) and male (82.4% vs 61.5%, P < .001) than
      other family physicians. Urban physicians who provided care to LTC residents had
      bigger LTC practices than rural LTC physicians did (median 50 residents vs median
      12 residents). CONCLUSION: About 600 family physicians are responsible for the
      regular care of more than 90% of LTC residents in Ontario and quality improvement
      efforts could be aimed at this relatively small group of physicians. Half of the
      urban physicians who practise in LTC homes are responsible for 50 or more LTC
      residents. This might represent a key part of their overall practice.

PMID- 23152466
TI  - Mystery of iron deficiency anemia.

PMID- 23152467
TI  - Social implications of tight glycemic control.

PMID- 23152468
TI  - Saying yes.

PMID- 23152470
TI  - Trauma and psoriatic arthritis: is there a relationship?

PMID- 23152471
TI  - Rural practice and the personal and educational characteristics of medical
      students: survey of 1269 graduates of the University of Manitoba.
AB  - OBJECTIVE: To describe the relationships between rural practice and the personal
      and medical education characteristics of medical students and residents. DESIGN:
      Cross-sectional, mailed survey. SETTING: Manitoba. PARTICIPANTS: Of 2578
      physician graduates of the University of Manitoba from 1965 to 2000 who were
      surveyed, 1269 (49%) responded. MAIN OUTCOME MEASURES: Whether physicians had
      ever practised in rural settings, and their demographic characteristics and
      adolescent, medical school, and residency training experiences. Multivariate
      logistic regression models were used to determine variables jointly and
      independently associated with rural practice. RESULTS: Of 1269 respondents, 39%
      had practised in rural settings, including 58% of the 362 respondents who
      identified family practice as their primary career activity, and 32% of the 907
      respondents whose primary activities were other than family practice. For all
      graduates, being male (P = .0289), having lived in a rural community (P < .0001),
      having attended a rural high school (P < .0001), and having rural educational
      experiences during medical school (P = .0068) or during postgraduate training (P
      < .0001) were significantly related to a greater likelihood of rural practice. In
      the final multivariate model, graduates of rural high schools, compared with
      those from urban public schools, were 1.57 times (95% CI 1.09 to 2.26) more
      likely to have practised in rural settings. Graduates who undertook part of their
      undergraduate training in rural settings were 1.34 times (95% CI 1.09 to 1.75)
      more likely to practise in rural locations. For both undergraduates and
      residents, the distance of their rural education experiences from Winnipeg and
      the likelihood of rural practice were directly related. For both FPs and non-FPs,
      being male and undertaking rural education during residency training were
      associated with a greater likelihood of rural practice, as was the distance of
      the training experience from the urban setting. For non-FPs a similar association
      was observed with undergraduate rural experiences. CONCLUSION: This large survey
      of graduates from a Canadian medical school demonstrated that attending a rural
      high school (P < .0001) and having rural educational exposure during medical
      school and residency training (P = .0068) were significantly associated with a
      physician practising in a rural location. That is, rural educational experiences
      on the continuum from high school through residency training appeared to be
      associated with rural practice.

PMID- 23152472
TI  - Factors influencing medical students' choice of family medicine: effects of rural
      versus urban background.
AB  - OBJECTIVE: To identify factors that influence medical students' choice of family
      medicine versus another specialty and to analyze influential factors by urban
      versus rural background of students. DESIGN: Cross-sectional questionnaire survey
      conducted in 2010. SETTING: University of Alberta in Edmonton. PARTICIPANTS: A
      total of 118 first-, 120 second-, and 107 third-year medical students. MAIN
      OUTCOME MEASURES: Twenty-two factors influencing preferred career choice, type of
      community lived in (rural vs. urban), and student age and sex. RESULTS: Overall,
      283 (82.0%) students responded to the survey. Those who preferred family medicine
      rather than another specialty as a career option were older (>= 25 years) (69.6%
      vs. 40.9%, P < .001), female (69.6% vs. 39.3%, P < .001), and had previously
      lived in rural locations (< 25,000 population) (46.8% vs. 23.9%, P < .001). Four
      factors were significantly associated with students preferring family medicine
      compared with any other specialty: emphasis on continuity of care (87.3 vs.
      45.3%, P < .001); length of residency (73.4% vs. 25.9%, P < .001); influence of
      family, friends, or community (67.1% vs. 50.2%, P = .011); and preference for
      working in a rural community (41.8% vs. 10.9%, P < .001). For students with urban
      backgrounds, the preference for family medicine was more strongly influenced by
      the opportunity to deal with a variety of medical problems; current debt load;
      and family, friends, or community than for those with rural backgrounds. Practice
      location preferences also differed between students from rural and urban
      backgrounds. CONCLUSION: Medical students who prefer family medicine as a career
      choice appear to be influenced by a different set of factors than those who
      prefer other specialties. Being female; being older; having previously lived in a
      rural location; placing importance on continuity of care; desire for a shorter
      residency; and influence of family, friends, or community are associated with
      medical students preferring family medicine. Some differences in factors
      influencing career choice exist between medical students from rural versus urban
      backgrounds. To increase the supply of family physicians, medical schools might
      consider introducing elements into the admissions process and the medical
      curriculum that encourage family medicine as a career choice.

PMID- 23152473
TI  - Does better access to FPs decrease the likelihood of emergency department use?
      Results from the Primary Care Access Survey.
AB  - OBJECTIVE: To determine whether better access to FP services decreases the
      likelihood of emergency department (ED) use among the Ontario population. DESIGN:
      Population-based telephone survey. SETTING: Ontario. PARTICIPANTS: A total of
      8502 Ontario residents aged 16 years and older. MAIN OUTCOME MEASURES: Emergency
      department use in the 12 months before the survey. RESULTS: Among the general
      population, having a regular FP was associated with having better access to FPs
      for immediate care (P < .001) but was not associated with a decreased likelihood
      of ED visits (odds ratio [OR] = 1.49, P = .03). Better actual access to FP
      services for immediate care was associated with a decreased likelihood of ED use
      (OR = 0.62, P < .001) among the general population. Among those with chronic
      diseases, having a regular FP was associated with a decreased likelihood of ED
      use (OR = 0.47, P = .01). Of the Ontario population, 39.3% wanted to see FPs for
      immediate care at least once a year; 63.1% of them had seen FPs without
      difficulties and were significantly less likely to use EDs than those who did not
      see FPs or had difficulties accessing physicians when needed (OR = 0.62, P <
      .001). Having a chronic health condition, recent immigrant status, residence in
      rural and northern parts of Ontario, and lower educational and income levels were
      significant predictors of a higher likelihood of ED use, independent of access to
      FPs (P < .05). CONCLUSION: A decreased likelihood of ED use is strongly
      associated with having a regular FP among those with chronic diseases and with
      having access to FPs for immediate care among the general population. Further
      research is needed to understand what accounts for a higher likelihood of ED use
      among those with regular FPs, new immigrants, residents of northern and rural
      areas of Ontario, and people with low socioeconomic status when actual access and
      sociodemographic characteristics have been taken into consideration. More
      important, this study demonstrates a need of distinguishing between potential and
      actual access to care, as having a regular FP and having timely and effective
      access to FP care might mean different things and have different effects on ED
      use.

PMID- 23152474
TI  - Determinants of first practice location: among Manitoba medical graduates.
AB  - OBJECTIVE: To help understand physician movement out of Manitoba by determining
      the factors that influence Manitoba medical graduates' choices about practice
      locations. DESIGN: Cross-sectional, within-stage, mixed-model survey. SETTING:
      Manitoba. PARTICIPANTS: All University of Manitoba medical graduates from classes
      1998 to 2009 for whom we had valid contact information (N = 912 of 943 graduates)
      were invited in August 2009 to participate in a survey. MAIN OUTCOME MEASURES:
      Demographic information; ratings, on a 5-point scale, of the importance when
      choosing first practice locations of 12 practice characteristics, 3 recruitment
      strategies, and 4 location characteristics listed in the survey; free-text
      narratives on unlisted factors; and estimates of likely practice location upon
      completion of training for recent graduates still in residency training. RESULTS:
      Completed surveys were received from 331 (35.1%) graduates of the surveyed
      classes, 162 (53.3%) of whom chose Manitoba for their first practice location.
      Multiple regression analyses indicated that graduates choosing Manitoba for their
      first practice location were significantly more likely to have done their
      residency training in Manitoba (P < .05), whether or not they gave a high rating
      to the importance of being near family and friends. Also, graduates choosing
      Manitoba were significantly more likely to be recent graduates (P = .007) and
      less likely to be members of a visible minority (P = .018). These associations
      were robust even when analyses were restricted to responses from practitioners
      without cause to estimate practice locations. Early self-selection of graduates
      during entry into specific residency programs, results of the residency match
      process, and "putting down roots" during residency years were 3 important
      interrelated themes identified through qualitative analyses. CONCLUSION:
      Residency education in Manitoba is the overwhelming factor influencing graduates'
      choice of Manitoba as their first practice location, regardless of graduates'
      rating of the importance of being near family or friends. Graduates' narratives
      provided insights into the complexities of choosing practice locations and
      enhanced the interpretive and theoretical validity of the study findings. More
      extensive studies involving all Canadian residents could further define the role
      residency location plays in physician practice location.

PMID- 23152475
TI  - Mood and sexual side effects of hormonal contraception: physicians' and
      residents' knowledge, attitudes, and practices.
AB  - OBJECTIVE: To explore physicians' knowledge, attitudes, and practices related to
      sexual and mood side effects of hormonal contraceptives, and to compare residents
      with practising doctors. DESIGN: A mixed-method study with faxed or e-mailed
      surveys and semistructured telephone interviews. SETTING: British Columbia.
      PARTICIPANTS: A random sample of family doctors, all gynecologists, and all
      residents in family medicine and gynecology in the College of Physicians and
      Surgeons of British Columbia registry. A subsample was interviewed. MAIN OUTCOME
      MEASURES: Estimates of rates of mood and sexual side effects of contraceptives in
      the practice population and how the physicians informed and advised patients
      about these side effects. RESULTS: There were 79 residents and 76 practising
      doctors who completed the questionnaires (response rates of 42.0% and 54.7% of
      eligible residents and physicians, respectively). The reference sources most
      physicians reported using gave the rates of sexual and mood side effects of
      hormonal contraceptives as less than 1%, and yet only 1 (0.6%) respondent
      estimated similar rates for mood side effects, and 12 (7.8%) for sexual effects
      among their patients. The most common answers were rates of 5% to 10%, with
      residents reporting similar rates to practising doctors. Practising doctors were
      more likely to ask about sexual and mood side effects than residents were (81.1%
      vs. 24.1% and 86.3% vs. 40.5%, respectively; P < .001). Practising doctors were
      also more likely to recommend switching to barrier methods (37.3% vs. 16.5%; P =
      .003) or intrauterine devices (54.7% vs. 38.0%; P = .038) than residents were and
      more likely to give more responses to the question about how they managed sexual
      and mood side effects (mean of 1.7 vs. 1.1 responses, P = .001). In 14 of the 15
      interviews, practising doctors discussed how they had learned about side effects
      mainly from their patients and how this had changed their practices. CONCLUSION:
      Physicians' perceived rates of mood and sexual side effects from hormonal
      contraception in the general population were higher than the rate of less than 1%
      quoted in the product monographs. Practising doctors reported that they learned
      about the type, frequency, and severity of side effects from their patients.

PMID- 23152478
TI  - Two cases of macrolide resistance in Mycoplasma pneumoniae acquired during the
      treatment period.

PMID- 23152477
TI  - Identification of the BCAR1-CFDP1-TMEM170A locus as a determinant of carotid
      intima-media thickness and coronary artery disease risk.
AB  - BACKGROUND: Carotid intima-media thickness (cIMT) is a widely accepted marker of
      subclinical atherosclerosis. To date, large-scale investigations of genetic
      determinants of cIMT are sparse. METHODS AND RESULTS: To identify cIMT-associated
      genes and genetic variants, a discovery analysis using the Illumina 200K
      CardioMetabochip was conducted in 3430 subjects with detailed ultrasonographic
      determinations of cIMT from the IMPROVE (Carotid Intima Media Thickness [IMT] and
      IMT-Progression as Predictors of Vascular Events in a High Risk European
      Population) study. Segment-specific IMT measurements of common carotid,
      bifurcation, and internal carotid arteries, and composite IMT variables
      considering the whole carotid tree (IMT(mean), IMT(max), and IMT(mean-max)), were
      analyzed. A replication stage investigating 42 single-nucleotide polymorphisms
      for association with common carotid IMT was undertaken in 5 independent European
      cohorts (total n=11,590). A locus on chromosome 16 (lead single-nucleotide
      polymorphism rs4888378, intronic in CFDP1) was associated with cIMT at
      significance levels passing multiple testing correction at both stages (array
      wide significant discovery P=6.75 * 10(-7) for IMT(max); replication P=7.24*10(
      6) for common cIMT; adjustments for sex, age, and population substructure where
      applicable; minor allele frequency 0.43 and 0.41, respectively). The protective
      minor allele was associated with lower carotid plaque score in a replication
      cohort (P=0.04, n=2120) and lower coronary artery disease risk in 2 case-control
      studies of subjects with European ancestry (odds ratio [95% confidence interval]
      0.83 [0.77-0.90], P=6.53 * 10(-6), n=13 591; and 0.95 [0.92-0.98], P=1.83 * 10(
      4), n=82 297, respectively). Queries of human biobank data sets revealed
      associations of rs4888378 with nearby gene expression in vascular tissues (n=126
      138). CONCLUSIONS: This study identified rs4888378 in the BCAR1-CFDP1-TMEM170A
      locus as a novel genetic determinant of cIMT and coronary artery disease risk in
      individuals of European descent.

PMID- 23152479
TI  - Acquisition of plasmid-borne blaIMP-19 gene by a VIM-1-positive Pseudomonas
      aeruginosa of the sequence type 235 epidemic lineage.

PMID- 23152481
TI  - Confronting the threat of multidrug-resistant Gram-negative bacteria in
      critically ill patients.
AB  - The re-emergence of infection due to multidrug-resistant Gram-negative bacteria
      in critically ill patients presents particular challenges to clinicians, given
      the lack of a pipeline of new antibiotics active against these resistant strains.
      Infected patients have a worse outcome than non-infected patients, although the
      additional contribution of antimicrobial resistance is less easy to define. Newer
      and better antibiotics would be welcome, but are unlikely alone to make a major
      impact on clinical outcomes.

PMID- 23152482
TI  - Evaluation of the combination of daptomycin and nafcillin against vancomycin
      intermediate Staphylococcus aureus.
AB  - OBJECTIVES: Continued selective pressure from glycopeptide use has led to non
      susceptible strains of Staphylococcus aureus, including vancomycin-intermediate
      S. aureus (VISA). Though relatively uncommon, VISA presents a particularly
      difficult clinical challenge when it arises. Pertinent to this investigation is
      the correlation between vancomycin intermediacy and daptomycin non
      susceptibility. The aim of this study was to evaluate the potential for synergy
      between daptomycin and nafcillin against VISA. METHODS: Twenty VISA strains were
      evaluated for daptomycin and nafcillin MICs by broth microdilution in duplicate.
      Potential for synergy was assessed by time-kill at 0.5* MIC in triplicate. Four
      strains displaying synergy in time-kill analysis were analysed in an in vitro
      pharmacokinetic (PK)/pharmacodynamic (PD) model in duplicate over 72 h. RESULTS:
      In time-kill experiments, 55% of strains (11/20) displayed synergy with the
      combination. In the PK/PD model, no differences between daptomycin-alone and
      combination regimens were observed for the strain with the lowest daptomycin MIC
      (0.5 mg/L). For the strain with a daptomycin MIC of 1 mg/L, 6 mg/kg
      daptomycin+nafcillin was superior to 6 mg/kg daptomycin alone (P=0.002) and 10
      mg/kg daptomycin+nafcillin was superior to all other regimens (P <= 0.004). When
      the daptomycin MIC increased to 2 mg/L, 10 mg/kg daptomycin+nafcillin was
      superior to 6 mg/kg daptomycin+nafcillin, which was superior to both 6 and 10
      mg/kg daptomycin alone (P <= 0.019). CONCLUSIONS: Daptomycin and nafcillin in
      combination significantly improved antibacterial activity against VISA. This
      effect was more pronounced as the daptomycin susceptibility of the strain
      declined.

PMID- 23152483
TI  - Combination therapy for gonorrhoea: in vitro synergy testing.
AB  - OBJECTIVES: Antimicrobial resistance in Neisseria gonorrhoeae is an increasing
      problem worldwide and combinations of antimicrobial agents have been recommended
      to delay the onset of treatment failures. The objective of this study was to
      obtain in vitro data on the activity of current (ceftriaxone or cefixime plus
      azithromycin) and alternative (gentamicin plus azithromycin) regimens. METHODS: A
      panel of 64 gonococcal isolates displaying various cefixime MICs was selected for
      inclusion in the study. Determination of the activities of the antimicrobial
      combinations of ceftriaxone, cefixime or gentamicin with azithromycin was
      performed using the agar dilution method and subsequent calculation of the
      fractional inhibitory concentration index (FICI) values. RESULTS: No antagonism
      for any of the antimicrobial combinations was detected among the 64 gonococcal
      isolates. When cefixime or ceftriaxone was combined with azithromycin all
      isolates showed additivity/indifference with a mean FICI of 2.0. All gonococcal
      isolates also showed additivity/indifference with the antimicrobial combination
      of gentamicin with azithromycin, but with a lower mean FICI of 1.7. No
      significant difference in the mean FICI between isolates fully susceptible to
      cefixime and isolates with decreased susceptibility to cefixime was observed.
      CONCLUSIONS: The results obtained support the gonorrhoea treatment currently
      recommended in the UK national guidelines and suggest that gentamicin with
      azithromycin could be a future treatment option. The in vivo activity and
      efficacy of these combinations remain unknown and prospective clinical studies
      should be addressed.

PMID- 23152484
TI  - Detection of the carbapenemase GIM-1 in Enterobacter cloacae in Germany.
AB  - OBJECTIVES: To characterize the mechanisms involved in reduced susceptibility to
      carbapenems in two Enterobacter cloacae clinical isolates. METHODS: Two E.
      cloacae isolates recovered from different regions in Germany and showing reduced
      susceptibility to carbapenems were analysed. Susceptibility testing, conjugation,
      transformation assays, plasmid analysis, sequencing and molecular typing using
      rep-PCR were performed. RESULTS: The two clinical isolates carried the bla(GIM-1)
      gene and showed resistance to ertapenem, with variable MIC values of imipenem and
      meropenem. The isolates were clonally unrelated. The bla(GIM-1) gene was located
      on self-transferable and non-typeable plasmids. Both isolates harboured distinct
      plasmids and integron structures containing the bla(GIM-1) gene cassette.
      Interestingly, one of the two plasmids was able to replicate in Pseudomonas
      aeruginosa, demonstrating its broad host range. CONCLUSIONS: This is the first
      identification in E. cloacae of the bla(GIM-1) gene, which is responsible for
      reduced susceptibility to carbapenems. We showed that this gene, previously
      identified in P. aeruginosa, was located in a different genetic background in E.
      cloacae. The bla(GIM-1) gene might spread quite efficiently in Enterobacteriaceae
      and P. aeruginosa, as it is difficult to detect and in addition is located on
      conjugative plasmids.

PMID- 23152485
TI  - In vitro effects of the CCR5 inhibitor maraviroc on human T cell function.
AB  - BACKGROUND: Several potential immunological benefits have been observed during
      treatment with the CC chemokine receptor 5 (CCR5) antagonist maraviroc, in
      addition to its antiviral effect. Our objective was to analyse the in vitro
      effects of CCR5 blockade on T lymphocyte function and homeostasis. METHODS:
      Peripheral blood mononuclear cells (PBMCs) from both HIV-negative (n=28) and
      treated HIV-positive (n=27) individuals were exposed in vitro to different
      concentrations of maraviroc (0.1-100 MUM). Effects on T cell activation were
      analysed by measuring the expression of the CD69, CD38, HLA-DR and CD25 receptors
      as well as CCR5 density using flow cytometry. Spontaneous and chemokine-induced
      chemotaxis were measured by transwell migration assays, and polyclonal-induced
      proliferation was assessed by a lymphoproliferation assay and carboxyfluorescein
      succinimidyl ester staining. RESULTS: Maraviroc increases CCR5 surface expression
      on activated T cells, even at low doses (0.1 MUM). Slight differences were
      detected in the frequency and mean fluorescence intensity of activation markers
      at high concentrations of maraviroc. Expression of CD25, CD38 and HLA-DR tended
      to decrease in both CD4+ and CD8+ T lymphocytes, whereas expression of CD69
      tended to increase. Maraviroc clearly inhibits T cell migration induced by
      chemokines in a dose-dependent manner. Moreover, at 100 MUM, maraviroc tends to
      inhibit T cell proliferation. CONCLUSIONS: These data showed that in vitro
      exposure to maraviroc decreases some activation expression markers on T
      lymphocytes and also migration towards chemoattractants. These results support
      the additional immunological effects of CCR5 blockade and suggest that maraviroc
      might have potential capacity to inhibit HIV-associated chronic inflammation and
      activation, both by directly affecting T cell activation and by reducing
      entrapment of lymphocytes in lymph nodes.

PMID- 23152486
TI  - Letter to the Editor, "Distribution of caries in children: variations between and
      within populations".

PMID- 23152480
TI  - Role and evolution of viral tropism in patients with advanced HIV disease
      receiving intensified initial regimen in the ANRS 130 APOLLO trial.
AB  - OBJECTIVES: The aims of the study were to assess in patients with advanced HIV
      disease receiving antiretroviral therapy (ART) intensification with enfuvirtide
      (i) resistance at virological failure (VF), (ii) impact of baseline tropism on
      immunovirological response, and (iii) HIV-1 DNA tropism evolution during ART.
      METHODS: The ANRS 130 APOLLO randomized trial evaluated in naive patients the
      immunovirological impact of standard ART without (control arm) or with
      enfuvirtide. Tropism was determined on RNA and DNA by V3-loop sequencing
      interpreted using the Geno2Pheno algorithm. RESULTS: At baseline the median CD4
      cell count was 30 cells/mm(3). Among the 170 patients assessable in this
      virological substudy, HIV-1 RNA tropism was as follows: 60% of viruses were R5
      and 40% were R5X4/X4. HIV-1 DNA tropism was as follows: 54% were R5 and 46% were
      R5X4/X4. At week 24, 39% and 49% of patients experienced VF in the enfuvirtide
      and control arms, respectively. In the enfuvirtide arm, only resistance
      associated mutations to enfuvirtide were detected. In the control arm, two
      patients displayed drug-resistant viruses at the time of VF. No impact of
      baseline tropism was observed on immunovirological response, regardless of the
      study arm. Among the 25 patients experiencing DNA tropism switch between baseline
      and week 24, 16 (64%) switched from R5 to R5X4/X4. These latter were mostly
      successfully suppressed patients receiving enfuvirtide and exhibiting poorer
      immunological response. CONCLUSIONS: Baseline RNA tropism had no impact on the
      immunovirological response. Drug resistance mutations were only detected for the
      fusion inhibitor. Finally, the mechanism of replenishment of the viral cellular
      reservoir with X4 viruses observed needs to be further analysed.

PMID- 23152489
TI  - Increased formation of monocyte-platelet aggregates in ischemic heart failure.
AB  - BACKGROUND: Cross-talk between monocytes and platelets is reflected by the
      formation of monocyte-platelet aggregates (MPAs). It is not known whether MPAs
      are affected in heart failure (HF), and we examined differences in patients with
      acute HF (AHF), stable HF (SHF), stable coronary artery disease (CAD) without HF,
      and healthy controls (HCs). METHODS AND RESULTS: MPAs were analyzed by flow
      cytometry for the 3 monocyte subsets (CD14++CD16-CCR2+ [Mon1], CD14++CD16+CCR2+
      [Mon2] and CD14+CD16++CCR2- [Mon3]) in patients with AHF (n=51), SHF (n=42),
      stable CAD (n=44), and HCs (n=40). Counts of total MPA and MPAs associated with
      Mon1 and Mon2 were significantly higher in AHF compared with SHF, CAD, and HCs
      (P<0.001 for all). The proportion of Mon1 aggregated with platelets was increased
      in AHF compared with SHF (P=0.033), CAD (P<0.001), and HCs (P<0.001). A higher
      percentage of Mon3 aggregated with platelets was also seen in AHF compared with
      SHF (P=0.012) and HCs (P<0.001) but not compared with CAD (P=0.647). MPAs
      associated with Mon2 were significantly lower in patients who experienced adverse
      clinical outcomes of death or rehospitalization compared with those who remained
      free of events (P=0.03). Mon2 count remained an independent negative predictor of
      combined death and rehospitalization after adjustment for age, left ventricular
      ejection fraction, creatinine, and brain natriuretic peptide (hazard ratio, 0.58
      [95% CI, 0.34-0.98]; P=0.043). CONCLUSIONS: MPA formation in patients with both
      acute and stable HF is increased and seems to be confined to monocytes from Mon1
      and Mon2 subsets. MPAs associated with Mon2 seem to be negatively predictive of a
      worse prognosis in AHF.

PMID- 23152488
TI  - Metabolic gene remodeling and mitochondrial dysfunction in failing right
      ventricular hypertrophy secondary to pulmonary arterial hypertension.
AB  - BACKGROUND: Right ventricular (RV) dysfunction (RVD) is the most frequent cause
      of death in patients with pulmonary arterial hypertension. Although abnormal
      energy substrate use has been implicated in the development of chronic left heart
      failure, data describing such metabolic remodeling in RVD remain incomplete.
      Thus, we sought to characterize metabolic gene expression changes and
      mitochondrial dysfunction in functional and dysfunctional RV hypertrophy. METHODS
      AND RESULTS: Two different rat models of RV hypertrophy were studied. The model
      of RVD (SU5416/hypoxia) exhibited a significantly decreased gene expression of
      peroxisome proliferator-activated receptor-gamma coactivator-1alpha, peroxisome
      proliferator-activated receptor-alpha and estrogen-related receptor-alpha. The
      expression of multiple peroxisome proliferator-activated receptor-gamma
      coactivator-1alpha target genes required for fatty acid oxidation was similarly
      decreased. Decreased peroxisome proliferator-activated receptor-gamma coactivator
      1alpha expression was also associated with a net loss of mitochondrial protein
      and oxidative capacity. Reduced mitochondrial number was associated with a
      downregulation of transcription factor A, mitochondrial, and other genes required
      for mitochondrial biogenesis. Electron microscopy demonstrated that, in RVD
      tissue, mitochondria had abnormal shape and size. Lastly, respirometric analysis
      demonstrated that mitochondria isolated from RVD tissue had a significantly
      reduced ADP-stimulated (state 3) rate for complex I. Conversely, functional RV
      hypertrophy in the pulmonary artery banding model showed normal expression of
      peroxisome proliferator-activated receptor-gamma coactivator-1alpha, whereas the
      expression of fatty acid oxidation genes was either preserved or unregulated.
      Moreover, pulmonary artery banding-RV tissue exhibited preserved transcription
      factor A mitochondrial expression and mitochondrial respiration despite elevated
      RV pressure-overload. CONCLUSIONS: Right ventricular dysfunction, but not
      functional RV hypertrophy in rats, demonstrates a gene expression profile
      compatible with a multilevel impairment of fatty acid metabolism and significant
      mitochondrial dysfunction, partially independent of chronic pressure-overload.

PMID- 23152490
TI  - Predictors of mortality in 6975 patients with chronic heart failure in the Gruppo
      Italiano per lo Studio della Streptochinasi nell'Infarto Miocardico-Heart Failure
      trial: proposal for a nomogram.
AB  - BACKGROUND: We developed a prognostic model to assess the risk of all-cause
      mortality in patients with chronic heart failure. METHODS AND RESULTS: We
      examined 6975 patients with chronic heart failure enrolled in the Gruppo Italiano
      per lo Studio della Streptochinasi nell'Infarto Miocardico-Heart Failure (GISSI
      HF) trial (3.9 years follow-up). Multivariable Cox regression models were
      developed to predict mortality (1969 deaths). By stepwise selection, the full
      final model included 25 predictors. A reduced model, considering the most
      significant variables ranked according to the Wald chi(2) (P<0.0001) accounted
      for most of the prognostic information. Internal validation of the model was
      performed with bootstrap techniques. The discrimination ability of the reduced
      model constituted by 12 factors (concordance probability estimate, 0.693) was as
      good as the full final model (concordance probability estimate, 0.70). Among the
      first 12 independent risk factors emerging in the reduced model, the 3 most
      powerful predictors were older age, higher New York Heart Association class, and
      lower estimated glomerular filtration rate. Other independent predictors that
      increased risk included lower left ventricular ejection fraction, chronic
      obstructive pulmonary disease, lower systolic blood pressure, diabetes mellitus,
      male sex, higher uricemia, lower body mass index, lower hemoglobin, and aortic
      stenosis. The reduced model was used to build a nomogram to estimate the risk of
      death in individual patients. In a subgroup of patients, the 2 well-known
      biomarkers (high-sensitivity cardiac troponin T and N-terminal pro-brain
      natriuretic peptide) emerged as the most powerful predictors of outcome.
      CONCLUSIONS: In a large contemporary population with chronic heart failure, this
      model offers good ability to assess the risk of death, confirming most of the
      risk factors that have emerged in recent trials. CLINICAL TRIAL REGISTRATION:
      URL: http://www.clinicaltrials.gov. Unique identifier: NCT00336336.

PMID- 23152491
TI  - Hemodynamic determinants of dyspnea improvement in acute decompensated heart
      failure.
AB  - BACKGROUND: Dyspnea relief constitutes a major treatment goal and a key measure
      of treatment efficacy in decompensated heart failure. However, there are no data
      with regard to the relationship between hemodynamic measurements during treatment
      and dyspnea improvement. METHODS AND RESULTS: We studied 233 patients assigned to
      right heart catheterization in the Vasodilation in the Management of Acute
      Congestive Heart Failure trial. Dyspnea (assessed using a 7-point Likert scale)
      and hemodynamic parameters were measured simultaneously at 15 and 30 minutes and
      1, 2, 3, 6, and 24 hours. Dyspnea relief was defined as moderate or marked
      improvement. There was a time-dependent association between the reductions in
      pulmonary capillary wedge pressure (PCWP; 25.4, 24.6, 24.0, 23.5, 23.4, 21.5, and
      19.9 mm Hg) and the percentage of patients achieving dyspnea relief (17.7%,
      24.6%, 32.2%, 36.2%, 37.8%, 47.4%, and 66.1%, in the respective time points).
      Multivariable logistic generalized estimating equations modeling demonstrated
      that reductions of both PCWP and mean pulmonary artery pressure were
      independently associated with dyspnea relief. Compared with the highest PCWP
      quartile, the adjusted odds ratios for dyspnea relief were 0.92 (95% confidence
      interval [CI], 0.67-1.29), 1.07 (95% CI, 0.75-1.55), and 1.80 (95% CI, 1.22-2.65)
      in the third, second, and first PCWP quartiles, respectively (P(trend)=0.003).
      Compared with the highest mean pulmonary artery pressure quartile, the adjusted
      odds ratios for dyspnea relief were 2.0 (95% CI, 1.41-2.82), 2.23 (95% CI, 1.52
      3.27), and 2.98 (95% CI, 1.91-4.66) in the third, second, and first mean
      pulmonary artery pressure quartiles, respectively (P(trend)<0.0001). CONCLUSIONS:
      A clinically significant improvement in dyspnea is associated with a reduction in
      both PCWP and mean pulmonary artery pressure.

PMID- 23152492
TI  - FoxO1 and FoxM1 transcription factors have antagonistic functions in neonatal
      cardiomyocyte cell-cycle withdrawal and IGF1 gene regulation.
AB  - RATIONALE: In the mammalian heart, cardiomyocytes withdraw from the cell cycle
      and initiate hypertrophic growth soon after birth, but the transcriptional
      regulatory mechanisms that control these neonatal transitions are not well
      defined. OBJECTIVE: Forkhead family transcription factors have been implicated as
      positive (forkhead box [Fox] transcription factor M1) and negative (FoxO1 and
      FoxO3) regulators of cardiomyocyte proliferation prenatally, but their regulatory
      interactions and functions in neonatal cell-cycle withdrawal have not been
      reported previously. Potential regulators of Fox activity, including the
      metabolic indicator AMP-activated protein kinase (AMPK), and Fox transcriptional
      targets (p21, p27, insulin-like growth factor 1 [IGF1]) also were examined.
      METHODS AND RESULTS: In cultured neonatal rat cardiomyocytes, AMPK activates
      FoxOs, and AMPK inhibition is sufficient to induce cell proliferation. In vivo,
      combined loss of FoxO1 and FoxO3 specifically in cardiomyocytes leads to delayed
      cell-cycle withdrawal and increased expression of IGF1 and FoxM1. Conversely,
      cardiomyocyte-specific loss of FoxM1 results in decreased neonatal cardiomyocyte
      cell proliferation, decreased expression of IGF1, and increased expression of
      cell-cycle inhibitors p21 and p27. IGF1 is a direct downstream target of cardiac
      Fox transcription factors, which is negatively regulated by FoxOs and positively
      regulated by FoxM1, dependent on AMPK activation status. CONCLUSIONS: These data
      support a regulatory mechanism whereby the balance of FoxO and FoxM1
      transcription factors integrates metabolic status, mediated by AMPK, and cell
      cycle regulation, through competitive regulation of target genes, including IGF1,
      in neonatal cardiomyocytes.

PMID- 23152493
TI  - Heterogeneity of ryanodine receptor dysfunction in a mouse model of
      catecholaminergic polymorphic ventricular tachycardia.
AB  - RATIONALE: Most cardiac ryanodine receptor (RyR2) mutations associated with
      catecholaminergic polymorphic ventricular tachycardia (CPVT) are postulated to
      cause a distinctive form of Ca(2+) release dysfunction. Considering the spread
      distribution of CPVT mutations, we hypothesized that dysfunctional heterogeneity
      also was feasible. OBJECTIVE: To determine the molecular and cellular mechanisms
      by which a novel RyR2-V2475F mutation associated with CPVT in humans triggers
      Ca(2+)-dependent arrhythmias in whole hearts and intact mice. METHODS AND
      RESULTS: Recombinant channels harboring CPVT-linked RyR2 mutations were
      functionally characterized using tritiated ryanodine binding and single-channel
      recordings. Homologous recombination was used to generate a knock-in mouse
      bearing the RyR2-V2475F mutation. Ventricular myocytes from mice heterozygous for
      the mutation (RyR2-V2475F(+/-)) and their wild-type littermates were Ca(2+)
      imaged by confocal microscopy under conditions that mimic stress. The propensity
      of wild-type and RyR2-V2475F(+/-) mice to have development of arrhythmias was
      tested at the whole heart level and in intact animals. Recombinant RyR2-V2475F
      channels displayed increased cytosolic Ca(2+) activation, abnormal protein kinase
      A phosphorylation, and increased activation by luminal Ca(2+). The RyR2-V2475F
      mutation appears embryonic-lethal in homozygous mice, but heterozygous mice have
      no alterations at baseline. Spontaneous Ca(2+) release events were more frequent
      and had shorter latency in isoproterenol-stimulated cardiomyocytes from RyR2
      V2475F(+/-) hearts, but their threshold was unchanged with respect to wild-type.
      Adrenergically triggered tachyarrhythmias were more frequent in RyR2-V2475F(+/-)
      mice. CONCLUSIONS: The mutation RyR2-V2475F is phenotypically strong among other
      CPVT mutations and produces heterogeneous mechanisms of RyR2 dysfunction. In
      living mice, this mutation appears too severe to be harbored in all RyR2 channels
      but remains undetected under basal conditions if expressed at relatively low
      levels. beta-adrenergic stimulation breaks the delicate Ca(2+) equilibrium of
      RyR2-V2475F(+/-) hearts and triggers life-threatening arrhythmias.

PMID- 23152494
TI  - High-density lipoprotein function, dysfunction, and reverse cholesterol
      transport.
AB  - Although high high-density lipoprotein (HDL)-cholesterol levels are associated
      with decreased cardiovascular risk in epidemiological studies, recent genetic and
      pharmacological findings have raised doubts about the beneficial effects of HDL.
      Raising HDL levels in animal models by infusion or overexpression of
      apolipoprotein A-I has shown clear vascular improvements, such as delayed
      atherosclerotic lesion progression and accelerated lesion regression, along with
      increased reverse cholesterol transport. Inflammation and other factors, such as
      myeloperoxidase-mediated oxidation, can impair HDL production and HDL function,
      with regard to its reverse cholesterol transport, antioxidant, and anti
      inflammatory activities. Thus, tests of HDL function, which have not yet been
      developed as routine diagnostic assays, may prove useful and be a better
      predictor of cardiovascular risk than HDL-cholesterol levels.

PMID- 23152495
TI  - Matrix rigidity activates Wnt signaling through down-regulation of Dickkopf-1
      protein.
AB  - Cells respond to changes in the physical properties of the extracellular matrix
      with altered behavior and gene expression, highlighting the important role of the
      microenvironment in the regulation of cell function. In the current study,
      culture of epithelial ovarian cancer cells on three-dimensional collagen I gels
      led to a dramatic down-regulation of the Wnt signaling inhibitor dickkopf-1 with
      a concomitant increase in nuclear beta-catenin and enhanced beta-catenin/Tcf/Lef
      transcriptional activity. Increased three-dimensional collagen gel invasion was
      accompanied by transcriptional up-regulation of the membrane-tethered collagenase
      membrane type 1 matrix metalloproteinase, and an inverse relationship between
      dickkopf-1 and membrane type 1 matrix metalloproteinase was observed in human
      epithelial ovarian cancer specimens. Similar results were obtained in other
      tissue-invasive cells such as vascular endothelial cells, suggesting a novel
      mechanism for functional coupling of matrix adhesion with Wnt signaling.

PMID- 23152496
TI  - Parkin protein deficiency exacerbates cardiac injury and reduces survival
      following myocardial infarction.
AB  - It is known that loss-of-function mutations in the gene encoding Parkin lead to
      development of Parkinson disease. Recently, Parkin was found to play an important
      role in the removal of dysfunctional mitochondria via autophagy in neurons.
      Although Parkin is expressed in the heart, its functional role in this tissue is
      largely unexplored. In this study, we have investigated the role of Parkin in the
      myocardium under normal physiological conditions and in response to myocardial
      infarction. We found that Parkin-deficient (Parkin(-/-)) mice had normal cardiac
      function for up to 12 months of age as determined by echocardiographic analysis.
      Although ultrastructural analysis revealed that Parkin-deficient hearts had
      disorganized mitochondrial networks and significantly smaller mitochondria,
      mitochondrial function was unaffected. However, Parkin(-/-) mice were much more
      sensitive to myocardial infarction when compared with wild type mice. Parkin(-/-)
      mice had reduced survival and developed larger infarcts when compared with wild
      type mice after the infarction. Interestingly, Parkin protein levels and
      mitochondrial autophagy (mitophagy) were rapidly increased in the border zone of
      the infarct in wild type mice. In contrast, Parkin(-/-) myocytes had reduced
      mitophagy and accumulated swollen, dysfunctional mitochondria after the
      infarction. Overexpression of Parkin in isolated cardiac myocytes also protected
      against hypoxia-mediated cell death, whereas nonfunctional Parkinson disease
      associated mutants ParkinR42P and ParkinG430D had no effect. Our results suggest
      that Parkin plays a critical role in adapting to stress in the myocardium by
      promoting removal of damaged mitochondria.

PMID- 23152497
TI  - Histone demethylase KDM6B promotes epithelial-mesenchymal transition.
AB  - Epithelial-mesenchymal transition (EMT) is a critical event that occurs in
      embryonic development, tissue repair control, organ fibrosis, and carcinoma
      invasion and metastasis. Although significant progress has been made in
      understanding the molecular regulation of EMT, little is known about how
      chromatin is modified in EMT. Chromatin modifications through histone acetylation
      and methylation determine the precise control of gene expression. Recently,
      histone demethylases were found to play important roles in gene expression
      through demethylating mono-, di-, or trimethylated lysines. KDM6B (also known as
      JMJD3) is a histone demethylase that might activate gene expression by removing
      repressive histone H3 lysine 27 trimethylation marks from chromatin. Here we
      report that KDM6B played a permissive role in TGF-beta-induced EMT in mammary
      epithelial cells by stimulating SNAI1 expression. KDM6B was induced by TGF-beta,
      and the knockdown of KDM6B inhibited EMT induced by TGF-beta. Conversely,
      overexpression of KDM6B induced the expression of mesenchymal genes and promoted
      EMT. Chromatin immunoprecipitation (ChIP) assays revealed that KDM6B promoted
      SNAI1 expression by removing histone H3 lysine trimethylation marks.
      Consistently, our analysis of the Oncomine database found that KDM6B expression
      was significantly increased in invasive breast carcinoma compared with normal
      breast tissues. The knockdown of KDM6B significantly inhibited breast cancer cell
      invasion. Collectively, our study uncovers a novel epigenetic mechanism
      regulating EMT and tumor cell invasion, and has important implication in
      targeting cancer metastasis.

PMID- 23152498
TI  - Sorting nexin 1 loss results in D5 dopamine receptor dysfunction in human renal
      proximal tubule cells and hypertension in mice.
AB  - The peripheral dopaminergic system plays a crucial role in blood pressure
      regulation through its actions on renal hemodynamics and epithelial ion
      transport. The dopamine D5 receptor (D(5)R) interacts with sorting nexin 1
      (SNX1), a protein involved in receptor retrieval from the trans-Golgi network. In
      this report, we elucidated the spatial, temporal, and functional significance of
      this interaction in human renal proximal tubule cells and HEK293 cells stably
      expressing human D(5)R and in mice. Silencing of SNX1 expression via RNAi
      resulted in the failure of D(5)R to internalize and bind GTP, blunting of the
      agonist-induced increase in cAMP production and decrease in sodium transport, and
      up-regulation of angiotensin II receptor expression, of which expression was
      previously shown to be negatively regulated by D(5)R. Moreover, siRNA-mediated
      depletion of renal SNX1 in C57BL/6J and BALB/cJ mice resulted in increased blood
      pressure and blunted natriuretic response to agonist in salt-loaded BALB/cJ mice.
      These data demonstrate a crucial role for SNX1 in D(5)R trafficking and that SNX1
      depletion results in D(5)R dysfunction and thus may represent a novel mechanism
      for the pathogenesis of essential hypertension.

PMID- 23152499
TI  - Hepatitis C virus NS5B and host cyclophilin A share a common binding site on
      NS5A.
AB  - Nonstructural protein 5B (NS5B) is essential for hepatitis C virus (HCV)
      replication as it carries the viral RNA-dependent RNA polymerase enzymatic
      activity. HCV replication occurs in a membrane-associated multiprotein complex in
      which HCV NS5A and host cyclophilin A (CypA) have been shown to be present
      together with the viral polymerase. We used NMR spectroscopy to perform a per
      residue level characterization of the molecular interactions between the unfolded
      domains 2 and 3 of NS5A (NS5A-D2 and NS5A-D3), CypA, and NS5B(Delta21). We show
      that three regions of NS5A-D2 (residues 250-262 (region A), 274-287 (region B),
      and 306-333 (region C)) interact with NS5B(Delta21), whereas NS5A-D3 does not. We
      show that both NS5B(Delta21) and CypA share a common binding site on NS5A that
      contains residues Pro-306 to Glu-323. No direct molecular interaction has been
      detected by NMR spectroscopy between HCV NS5B(Delta21) and host CypA. We show
      that cyclosporine A added to a sample containing NS5B(Delta21), NS5A-D2, and CypA
      specifically inhibits the interaction between CypA and NS5A-D2 without altering
      the one between NS5A-D2 and NS5B(Delta21). A high quality heteronuclear NMR
      spectrum of HCV NS5B(Delta21) has been obtained and was used to characterize the
      binding site on the polymerase of NS5A-D2. Moreover these data highlight the
      potential of using NMR of NS5B(Delta21) as a powerful tool to characterize in
      solution the interactions of the HCV polymerase with all kinds of molecules
      (proteins, inhibitors, RNA). This work brings new insights into the comprehension
      of the molecular interplay between NS5B, NS5A, and CypA, three essentials
      proteins for HCV replication.

PMID- 23152500
TI  - SUMO-specific protease 1 regulates mitochondrial biogenesis through PGC-1alpha.
AB  - Peroxisome proliferator-activated receptor gamma (PPARgamma) coactivator 1alpha
      (PGC-1alpha) is a master regulator of mitochondrial biogenesis in response to
      changes in the cellular environment, physiological or pathological status of
      mammals. PGC-1alpha is known to be modified by SUMO (Small Ubiquitin-like
      Modifier). However, it is not known whether SUMOylation could affect the function
      of PGC-1alpha in mitochondrial biogenesis and that how PGC-1alpha SUMOylation is
      regulated. In this study, we have identified the role of Sentrin/SUMO-specific
      protease 1 (SENP1) as a specific SUMO protease to regulate SUMOylation status of
      PGC-1alpha. More importantly, we have also found that SENP1 promotes PGC-1alpha
      transcription activity, which is essential for the expression of mitochondrial
      genes and subsequently mitochondrial biogenesis. Thus, we reveal that the
      SUMOylation of PGC-1alpha controlled by SENP1 plays an important role in
      mitochondrial biogenesis and function.

PMID- 23152501
TI  - A novel SUMO1-specific interacting motif in dipeptidyl peptidase 9 (DPP9) that is
      important for enzymatic regulation.
AB  - Sumoylation affects many cellular processes by regulating the interactions of
      modified targets with downstream effectors. Here we identified the cytosolic
      dipeptidyl peptidase 9 (DPP9) as a SUMO1 interacting protein. Surprisingly, DPP9
      binds to SUMO1 independent of the well known SUMO interacting motif, but instead
      interacts with a loop involving Glu(67) of SUMO1. Intriguingly, DPP9 selectively
      associates with SUMO1 and not SUMO2, due to a more positive charge in the SUMO1
      loop. We mapped the SUMO-binding site of DPP9 to an extended arm structure,
      predicted to directly flank the substrate entry site. Importantly, whereas
      mutants in the SUMO1-binding arm are less active compared with wild-type DPP9,
      SUMO1 stimulates DPP9 activity. Consistent with this, silencing of SUMO1 leads to
      a reduced cytosolic prolyl-peptidase activity. Taken together, these results
      suggest that SUMO1, or more likely, a sumoylated protein, acts as an allosteric
      regulator of DPP9.

PMID- 23152502
TI  - The size and conservation of a coiled-coil structure in the ectodomain of human
      BST-2/tetherin is dispensable for inhibition of HIV-1 virion release.
AB  - BST-2/CD317/tetherin is a host factor that inhibits HIV-1 release and is
      counteracted by HIV-1 Vpu. Structural studies indicate that the BST-2 ectodomain
      assumes a coiled-coil conformation. Here we studied the role of the BST-2
      ectodomain for tethering function. First, we addressed the importance of the
      length and structure of the ectodomain by adding or substituting heterologous
      coiled-coil or non-coiled-coil sequences. We found that extending or replacing
      the BST-2 ectodomain using non-coiled-coil sequences resulted in loss of BST-2
      function. Doubling the size of the BST-2 ectodomain by insertion of a
      heterologous coiled-coil motif or substituting the BST-2 coiled-coil domain with
      a heterologous coiled-coil motif maintained tethering function. Reductions in the
      size of the BST-2 coiled-coil domain were tolerated as well. In fact, deletion of
      the C-terminal half of the BST-2 ectodomain, including a series of seven
      consecutive heptad motifs did not abolish tethering function. However, slight
      changes in the positioning of deletions affecting the relative placing of charged
      or hydrophobic residues on the helix severely impacted the functional properties
      of BST-2. Overall, we conclude that the size of the BST-2 ectodomain is highly
      flexible and can be reduced or extended as long as the positioning of residues
      important for the stability of the dimer interface is maintained.

PMID- 23152503
TI  - Interplay between alpha-, beta-, and gamma-secretases determines biphasic amyloid
      beta protein level in the presence of a gamma-secretase inhibitor.
AB  - Amyloid-beta (Abeta) is produced by the consecutive cleavage of amyloid precursor
      protein (APP) first by beta-secretase, generating C99, and then by gamma
      secretase. APP is also cleaved by alpha-secretase. It is hypothesized that
      reducing the production of Abeta in the brain may slow the progression of
      Alzheimer disease. Therefore, different gamma-secretase inhibitors have been
      developed to reduce Abeta production. Paradoxically, it has been shown that low
      to moderate inhibitor concentrations cause a rise in Abeta production in
      different cell lines, in different animal models, and also in humans. A
      mechanistic understanding of the Abeta rise remains elusive. Here, a minimal
      mathematical model has been developed that quantitatively describes the Abeta
      dynamics in cell lines that exhibit the rise as well as in cell lines that do
      not. The model includes steps of APP processing through both the so-called
      amyloidogenic pathway and the so-called non-amyloidogenic pathway. It is shown
      that the cross-talk between these two pathways accounts for the increase in Abeta
      production in response to inhibitor, i.e. an increase in C99 will inhibit the non
      amyloidogenic pathway, redirecting APP to be cleaved by beta-secretase, leading
      to an additional increase in C99 that overcomes the loss in gamma-secretase
      activity. With a minor extension, the model also describes plasma Abeta profiles
      observed in humans upon dosing with a gamma-secretase inhibitor. In conclusion,
      this mechanistic model rationalizes a series of experimental results that spans
      from in vitro to in vivo and to humans. This has important implications for the
      development of drugs targeting Abeta production in Alzheimer disease.

PMID- 23152504
TI  - Bim, a proapoptotic protein, up-regulated via transcription factor E2F1-dependent
      mechanism, functions as a prosurvival molecule in cancer.
AB  - Proapoptotic Bcl-2 homology 3-only protein Bim plays an important role in Bax/Bak
      mediated cytochrome c release and apoptosis. Here, we provide evidence for a
      novel prosurvival function of Bim in cancer cells. Bim was constitutively
      overexpressed in multiple prostate and breast cancer cells as well as in primary
      tumor cells. Quantitative real time PCR analysis showed that Bim was
      transcriptionally up-regulated. We have identified eight endogenous E2F1-binding
      sites on the Bim promoter using in silico analysis. Luciferase assay demonstrated
      that Bim expression was E2F1-dependent as mutation of the E2F1-binding sites on
      the Bim promoter inhibited luciferase activities. In support, E2F1 silencing led
      to the loss of Bim expression in cancer cells. Bim primarily localized to
      mitochondrial and cytoskeleton-associated fractions. Bim silencing or
      microinjection of anti-Bim antibodies into the cell cytoplasm resulted in cell
      rounding, detachment, and subsequent apoptosis. We observed up-regulation of
      prosurvival proteins Bcl-xL and Mcl-1, which sequester Bim in cancer cells. In
      addition, a phosphorylated form of Bim was also elevated in cancer cells. These
      findings suggest that the constitutively overexpressed Bim may function as a
      prosurvival molecule in epithelial cancer cells, and phosphorylation and
      association with Bcl-xL/Mcl-1 block its proapoptotic functions.

PMID- 23152505
TI  - Increasing expression of microRNA 181 inhibits porcine reproductive and
      respiratory syndrome virus replication and has implications for controlling virus
      infection.
AB  - Porcine reproductive and respiratory syndrome virus (PRRSV) is one of the most
      important viral pathogens in the swine industry. Emerging evidence indicates that
      the host microRNAs (miRNAs) are involved in host-pathogen interactions. However,
      whether host miRNAs can target PRRSV and be used to inhibit PRRSV infection has
      not been reported. Recently, microRNA 181 (miR-181) has been identified as a
      positive regulator of immune response, and here we report that miR-181 can
      directly impair PRRSV infection. Our results showed that delivered miR-181 mimics
      can strongly inhibit PRRSV replication in vitro through specifically binding to a
      highly (over 96%) conserved region in the downstream of open reading frame 4
      (ORF4) of the viral genomic RNA. The inhibition of PRRSV replication was specific
      and dose dependent. In PRRSV-infected Marc-145 cells, the viral mRNAs could
      compete with miR-181-targeted sequence in luciferase vector to interact with miR
      181 and result in less inhibition of luciferase activity, further demonstrating
      the specific interactions between miR-181 and PRRSV RNAs. As expected, miR-181
      and other potential PRRSV-targeting miRNAs (such as miR-206) are expressed much
      more abundantly in minimally permissive cells or tissues than in highly
      permissive cells or tissues. Importantly, highly pathogenic PRRSV (HP-PRRSV)
      strain-infected pigs treated with miR-181 mimics showed substantially decreased
      viral loads in blood and relief from PRRSV-induced fever compared to negative
      control (NC)-treated controls. These results indicate the important role of host
      miRNAs in modulating PRRSV infection and viral pathogenesis and also support the
      idea that host miRNAs could be useful for RNA interference (RNAi)-mediated
      antiviral therapeutic strategies.

PMID- 23152506
TI  - A bovine herpesvirus 1 protein expressed in latently infected neurons (ORF2)
      promotes neurite sprouting in the presence of activated Notch1 or Notch3.
AB  - Bovine herpesvirus 1 (BHV-1) infection induces clinical symptoms in the upper
      respiratory tract, inhibits immune responses, and can lead to life-threatening
      secondary bacterial infections. Following acute infection, BHV-1 establishes
      latency in sensory neurons within trigeminal ganglia, but stress can induce
      reactivation from latency. The latency-related (LR) RNA is the only viral
      transcript abundantly expressed in latently infected sensory neurons. An LR
      mutant virus with stop codons at the amino terminus of the first open reading
      frame (ORF) in the LR gene (ORF2) is not reactivated from latency, in part
      because it induces higher levels of apoptosis in infected neurons. ORF2 inhibits
      apoptosis in transiently transfected cells, suggesting that it plays a crucial
      role in the latency-reactivation cycle. ORF2 also interacts with Notch1 or Notch3
      and inhibits its ability to trans activate certain viral promoters. Notch3 RNA
      and protein levels are increased during reactivation from latency, suggesting
      that Notch may promote reactivation. Activated Notch signaling interferes with
      neuronal differentiation, in part because neurite and axon generation is blocked.
      In this study, we demonstrated that ORF2 promotes neurite formation in mouse
      neuroblastoma cells overexpressing Notch1 or Notch3. ORF2 also interfered with
      Notch-mediated trans activation of the promoter that regulates the expression of
      Hairy Enhancer of Split 5, an inhibitor of neurite formation. Additional studies
      provided evidence that ORF2 promotes the degradation of Notch3, but not that of
      Notch1, in a proteasome-dependent manner. In summary, these studies suggest that
      ORF2 promotes a mature neuronal phenotype that enhances the survival of infected
      neurons and consequently increases the pool of latently infected neurons.

PMID- 23152507
TI  - Myxovirus resistance gene A (MxA) expression suppresses influenza A virus
      replication in alpha interferon-treated primate cells.
AB  - Alpha interferon (IFN-alpha) production is triggered when influenza virus RNA is
      detected by appropriate pattern recognition receptors in the host cell. IFN-alpha
      induces the expression of more than 300 interferon-stimulated genes (ISGs), and
      this blunts influenza virus replication. The human ISG MxA can inhibit influenza
      A virus replication in mouse cells by interfering with a step in the virus
      replication cycle after primary transcription of the negative-strand RNA genome
      to mRNA (J. Pavlovic, O. Haller, and P. Staeheli, J. Virol. 66:2564-2569, 1992).
      To determine the role of MxA in blocking human influenza A virus replication in
      primate cells, we manipulated MxA expression in rhesus kidney epithelial cells
      (LLC-MK(2)) and human lung carcinoma cells (A549). We found that IFN-alpha
      treatment prior to influenza virus infection suppressed virus replication and
      induced the expression of many ISGs, including MxA. However, IFN-alpha-mediated
      suppression of virus replication was abolished by small interfering RNA (siRNA)
      knockdown of MxA expression in IFN-treated cells. In addition, influenza virus
      replication was suppressed in Vero cells stably transfected with MxA. A strand
      specific reverse transcription-PCR (RT-PCR) assay showed that positive-strand
      influenza virus mRNA and negative-strand genomic RNA (gRNA) accumulated to high
      levels at 8 h after infection in control Vero cells containing the empty vector.
      However, in Vero cells stably transfected with MxA positive-strand influenza
      virus mRNA, complementary positive-strand influenza virus genome RNA (cRNA) and
      influenza virus gRNA were drastically suppressed. Thus, in primate cells, MxA
      inhibits human seasonal influenza virus replication at a step prior to primary
      transcription of gRNA into mRNA. Taken together, these results demonstrate that
      MxA mediates control of influenza virus replication in primate cells treated with
      IFN-alpha.

PMID- 23152508
TI  - Straightforward selection of broadly neutralizing single-domain antibodies
      targeting the conserved CD4 and coreceptor binding sites of HIV-1 gp120.
AB  - Few broadly neutralizing antibodies targeting determinants of the HIV-1 surface
      envelope glycoprotein (gp120) involved in sequential binding to host CD4 and
      chemokine receptors have been characterized. While these epitopes show low
      diversity among various isolates, HIV-1 employs many strategies to evade humoral
      immune response toward these sensitive sites, including a carbohydrate shield,
      low accessibility to these buried cavities, and conformational masking. Using
      trimeric gp140, free or bound to a CD4 mimic, as immunogens in llamas, we
      selected a panel of broadly neutralizing single-domain antibodies (sdAbs) that
      bind to either the CD4 or the coreceptor binding site (CD4BS and CoRBS,
      respectively). When analyzed as monomers or as homo- or heteromultimers, the best
      sdAb candidates could not only neutralize viruses carrying subtype B envelopes,
      corresponding to the Env molecule used for immunization and selection, but were
      also efficient in neutralizing a broad panel of envelopes from subtypes A, C, G,
      CRF01_AE, and CRF02_AG, including tier 3 viruses. Interestingly, sdAb multimers
      exhibited a broader neutralizing activity spectrum than the parental sdAb
      monomers. The extreme stability and high recombinant production yield combined
      with their broad neutralization capacity make these sdAbs new potential
      microbicide candidates for HIV-1 transmission prevention.

PMID- 23152509
TI  - Novel mutations in gB and gH circumvent the requirement for known gD Receptors in
      herpes simplex virus 1 entry and cell-to-cell spread.
AB  - Both entry and cell-to-cell spread of herpes simplex virus (HSV) involve a
      cascade of cooperative interactions among the essential glycoproteins D, B, and
      H/L (gD, gB, and gH/gL, respectively) initiated by the binding of gD to a cognate
      HSV entry receptor. We previously reported that a variant (D285N/A549T) of
      glycoprotein B (gB:NT) enabled primary virus entry into cells that were devoid of
      typical HSV entry receptors. Here, we compared the activities of the gB:NT
      variant with those of a newly selected variant of glycoprotein H (gH:KV) and a
      frequently coselected gB variant (gB:S668N). In combination, gH:KV and gB:S668N
      enabled primary virus entry into cells that lacked established HSV entry
      receptors as efficiently as did gB:NT, but separately, each variant enabled only
      limited entry. Remarkably, gH:KV uniquely facilitated secondary virus spread
      between cells that lacked canonical entry receptors. Transient expression of the
      four essential entry glycoproteins revealed that gH:KV, but not gB:NT, induced
      fusion between cells lacking the standard receptors. Because the involvement of
      gD remained essential for virus spread and cell fusion, we propose that gH:KV
      mimics a transition state of gH that responds efficiently to weak signals from gD
      to reach the active state. Computational modeling of the structures of wild-type
      gH and gH:KV revealed relatively subtle differences that may have accounted for
      our experimental findings. Our study shows that (i) the dependence of HSV-1 entry
      and spread on specific gD receptors can be reduced by sequence changes in the
      downstream effectors gB and gH, and (ii) the relative roles of gB and gH are
      different in entry and spread.

PMID- 23152510
TI  - Identification of contamination in the American type culture collection stock of
      human adenovirus type 8 by whole-genome sequencing.

PMID- 23152511
TI  - p38 and OGT sequestration into viral inclusion bodies in cells infected with
      human respiratory syncytial virus suppresses MK2 activities and stress granule
      assembly.
AB  - Respiratory syncytial virus (RSV) forms cytoplasmic inclusion bodies (IBs) that
      are thought to be sites of nucleocapsid accumulation and viral RNA synthesis. The
      present study found that IBs also were the sites of major sequestration of two
      proteins involved in cellular signaling pathways. These are phosphorylated p38
      mitogen-activated protein kinase (MAPK) (p38-P), a key regulator of cellular
      inflammatory and stress responses, and O-linked N-acetylglucosamine (OGN)
      transferase (OGT), an enzyme that catalyzes the posttranslational addition of OGN
      to protein targets to regulate cellular processes, including signal transduction,
      transcription, translation, and the stress response. The virus-induced
      sequestration of p38-P in IBs resulted in a substantial reduction in the
      accumulation of a downstream signaling substrate, MAPK-activated protein kinase 2
      (MK2). Sequestration of OGT in IBs was associated with suppression of stress
      granule (SG) formation. Thus, while the RSV IBs are thought to play an essential
      role in viral replication, the present results show that they also play a role in
      suppressing the cellular response to viral infection. The sequestration of p38-P
      and OGT in IBs appeared to be reversible: oxidative stress resulting from
      arsenite treatment transformed large IBs into a scattering of smaller bodies,
      suggestive of partial disassembly, and this was associated with MK2
      phosphorylation and OGN addition. Unexpectedly, the RSV M2-1 protein was found to
      localize in SGs that formed during oxidative stress. This protein was previously
      shown to be a viral transcription elongation factor, and the present findings
      provide the first evidence of possible involvement in SG activities during RSV
      infection.

PMID- 23152512
TI  - Characterization of hepatitis C virus recombinants with chimeric E1/E2 envelope
      proteins and identification of single amino acids in the E2 stem region important
      for entry.
AB  - The hepatitis C virus (HCV) envelope proteins E1 and E2 play a key role in host
      cell entry and represent important targets for vaccine and drug development.
      Here, we characterized HCV recombinants with chimeric E1/E2 complexes in vitro.
      Using genotype 1a/2a JFH1-based recombinants expressing 1a core-NS2, we exchanged
      E2 with functional isolate sequences of genotypes 1a (alternative isolate), 1b,
      and 2a. While the 1a-E2 exchange did not impact virus viability, the 2a-E2
      recombinant was nonviable. After E2 exchange from three 1b isolates, long delays
      were observed before spread of infection. For recovered 1b-E2 recombinants,
      single E2 stem region amino acid changes were identified at residues 706, 707,
      and 710. In reverse genetic studies, these mutations increased infectivity titers
      by ~100-fold, apparently without influencing particle stability or cell binding
      although introducing slight decrease in particle density. In addition, the 1b-E2
      exchange led to a decrease in secreted core protein of 25 to 50%, which was
      further reduced by the E2 stem region mutations. These findings indicated that
      compensatory mutations permitted robust infectious virus production, without
      increasing assembly/release. Studies of E1/E2 heterodimerization showed no
      differences in intracellular E1/E2 interaction for chimeric constructs with or
      without E2 stem region mutations. Interestingly, the E2 stem region mutations
      allowed efficient entry, which was verified in 1a-E1/1b-E2 HCV pseudoparticle
      assays. A CD81 inhibition assay indicated that the mutations influenced a late
      step of the HCV entry pathway. Overall, this study identified specific amino
      acids in the E2 stem region of importance for HCV entry and for production of
      infectious virus particles.

PMID- 23152513
TI  - Whole-genome sequencing of the Akata and Mutu Epstein-Barr virus strains.
AB  - Using a simple viral genome enrichment approach, we report the de novo assembly
      of the Akata and Mutu Epstein-Barr virus (EBV) genomes from a single lane of next
      generation sequencing (NGS) reads. The Akata and Mutu viral genomes are type I
      EBV strains of approximately 171 kb in length. Evidence for genome heterogeneity
      was found for the Akata but not for the Mutu strain. A comparative analysis of
      Akata with another four completely sequenced EBV strains, B95-8/Raji, AG876,
      Mutu, and GD1, demonstrated that the Akata strain is most closely related to the
      GD1 strain and exhibits the greatest divergence from the type II strain, AG876. A
      global comparison of latent and lytic gene sequences showed that the four latency
      genes, EBNA2, EBNA3A, EBNA3B, and EBNA3C, are uniquely defining of type I and
      type II strain differences. Within type I strains, LMP1, the latency gene, is
      among the most divergent of all EBV genes, with three insertion or deletion loci
      in its CTAR2 and CTAR3 signaling domains. Analysis of the BHLF1 and LF3 genes
      showed that the reading frames identified in the B95-8/Raji genome are not
      conserved in Akata (or Mutu, for BHLF1), suggesting a primarily non-protein
      coding function in EBV's life cycle. The Akata and Mutu viral-genome sequences
      should be a useful resource for homology-based functional prediction and for
      molecular studies, such as PCR, RNA-seq, recombineering, and transcriptome
      studies. As an illustration, we identified novel RNA-editing events in ebv-miR
      BART6 antisense transcripts using the Akata and Mutu reference genomes.

PMID- 23152514
TI  - Human papillomavirus E7 induces rereplication in response to DNA damage.
AB  - Human papillomavirus (HPV) infection is necessary but not sufficient for cervical
      carcinogenesis. Genomic instability caused by HPV allows cells to acquire
      additional mutations required for malignant transformation. Genomic instability
      in the form of polyploidy has been demonstrated to play an important role in
      cervical carcinogenesis. We have recently found that HPV-16 E7 oncogene induces
      polyploidy in response to DNA damage; however, the mechanism is not known. Here
      we present evidence demonstrating that HPV-16 E7-expressing cells have an intact
      G(2) checkpoint. Upon DNA damage, HPV-16 E7-expressing cells arrest at the G(2)
      checkpoint and then undergo rereplication, a process of successive rounds of host
      DNA replication without entering mitosis. Interestingly, the DNA replication
      initiation factor Cdt1, whose uncontrolled expression induces rereplication in
      human cancer cells, is upregulated in E7-expressing cells. Moreover,
      downregulation of Cdt1 impairs the ability of E7 to induce rereplication. These
      results demonstrate an important role for Cdt1 in HPV E7-induced rereplication
      and shed light on mechanisms by which HPV induces genomic instability.

PMID- 23152515
TI  - Critical roles of glucocorticoid-induced leucine zipper in infectious bursal
      disease virus (IBDV)-induced suppression of type I Interferon expression and
      enhancement of IBDV growth in host cells via interaction with VP4.
AB  - Infectious bursal disease (IBD) is an acute, highly contagious, and
      immunosuppressive avian disease caused by IBD virus (IBDV). Although IBDV-induced
      immunosuppression has been well established, the underlying exact molecular
      mechanism for such induction is not very clear. We report here the identification
      of IBDV VP4 as an interferon suppressor by interaction with the glucocorticoid
      induced leucine zipper (GILZ) in host cells. We found that VP4 suppressed the
      expression of type I interferon in HEK293T cells after tumor necrosis factor
      alpha (TNF-alpha) treatment or Sendai virus (SeV) infection and in DF-1 cells
      after poly(I.C) stimulation. In addition, the VP4-induced suppression of type I
      interferon could be completely abolished by knockdown of GILZ by small
      interfering RNA (siRNA). Furthermore, knockdown of GILZ significantly inhibited
      IBDV growth in host cells, and this inhibition could be markedly mitigated by
      anti-alpha/beta interferon antibodies in the cell cultures (P < 0.001). Thus, VP4
      induced suppression of type I interferon is mediated by interaction with GILZ, a
      protein that appears to inhibit cell responses to viral infection.

PMID- 23152516
TI  - Acetylation of conserved lysines in bovine papillomavirus E2 by p300.
AB  - The p300, CBP, and pCAF lysine acetyltransferase (KAT) proteins have been
      reported to physically interact with bovine (BPV) and human (HPV) papillomavirus
      E2 proteins. While overexpression of these KAT proteins enhances E2-dependent
      transcription, the mechanism has not been determined. Using RNA interference
      (RNAi) to deplete these factors, we demonstrated that E2 transcriptional activity
      requires physiological levels of p300, CBP, and pCAF. Each protein appears to
      have a unique function in E2-dependent transcription, since overexpression of one
      KAT failed to compensate for RNAi knockdown of another KAT. Using an in vitro
      acetylation assay, we identified highly conserved lysines that are targeted by
      p300 for acetylation. The conservative changes of lysines at positions 111 and
      112 to arginine were of particular interest. The K111R and the K111R/K112R
      mutants showed reduced transcriptional activity that was not responsive to p300
      overexpression, while the K112R mutant retained activity. p300 and CBP were
      detected at the viral promoter; however, pCAF was not. We propose a model by
      which E2 transcriptional activity is controlled by p300-mediated acetylation of
      lysine 111. This model represents a novel mechanism regulating papillomavirus
      gene expression.

PMID- 23152517
TI  - Identification and functional analysis of the novel ORF4 protein encoded by
      porcine circovirus type 2.
AB  - Porcine circovirus type 2 (PCV2) is the primary causative agent of porcine
      circovirus-associated diseases in pigs. To date, viral proteins Cap, Rep, Rep',
      and ORF3, encoded by the PCV2 genome, have been described. Here, transcription
      and translation of a novel viral gene within the PCV2 genome (designated ORF4)
      was determined and functionally analyzed in vitro and in vivo. Northern blot
      analysis indicated that the RNA transcribed from the ORF4 gene is about 180 bp in
      length and overlaps ORF3 in the same direction. Site-directed mutagenesis
      confirmed that the viral ORF4 protein is not essential for virus replication in
      PK-15 cells and in mice infected with an ORF4-deficient PCV2 (PCV2Delta).
      PCV2Delta triggered higher activity levels of caspase-3 and -8 than wild-type
      PCV2 (wPCV2) in PK-15 cells. The antigenic epitopes of two mouse monoclonal
      antibodies (MAbs) raised against the viral ORF4 protein were mapped to the same
      19KSSASPR25 peptide. Expression of ORF4 was confirmed using the specific MAbs in
      wPCV2-infected PK-15 cells and mice. Mice infected with PCV2Delta had a higher
      serum viral load (genomic copies) and more severe lymphoid tissue damage in the
      spleen than those infected with wPCV2. Meanwhile, flow-cytometric analysis
      indicated that the PCV2Delta infection caused a significant decrease of CD4(+)
      and CD8(+) T lymphocytes. Our results demonstrate that ORF4 is a newly discovered
      viral protein that is not essential for PCV2 replication but plays a role in
      suppressing caspase activity and regulating CD4(+) and CD8(+) T lymphocytes
      during PCV2 infection.

PMID- 23152519
TI  - The hemagglutinin protein of highly pathogenic H5N1 influenza viruses overcomes
      an early block in the replication cycle to promote productive replication in
      macrophages.
AB  - Macrophages are known to be one of the first lines of defense against influenza
      virus infection. However, they may also contribute to severe disease caused by
      the highly pathogenic avian (HPAI) H5N1 influenza viruses. One reason for this
      may be the ability of certain influenza virus strains to productively replicate
      in macrophages. However, studies investigating the productive replication of
      influenza viruses in macrophages have been contradictory, and the results may
      depend on both the type of macrophages used and the specific viral strain. In
      this work, we investigated the ability of H1 to H16 viruses to productively
      replicate in primary murine alveolar macrophages and RAW264.7 macrophages. We
      show that only a subset of HPAI H5N1 viruses, those that cause high morbidity and
      mortality in mammals, can productively replicate in macrophages, as measured by
      the release of newly synthesized virus particles into the cell supernatant.
      Mechanistically, we found that these H5 strains can overcome a block early in the
      viral life cycle leading to efficient nuclear entry, viral transcription,
      translation, and ultimately replication. Studies with reassortant viruses
      demonstrated that expression of the hemagglutinin gene from an H5N1 virus rescued
      replication of H1N1 influenza virus in macrophages. This study is the first to
      characterize H5N1 influenza viruses as the only subtype of influenza virus
      capable of productive replication in macrophages and establishes the viral gene
      that is required for this characteristic. The ability to productively replicate
      in macrophages is unique to H5N1 influenza viruses and may contribute to their
      increased pathogenesis.

PMID- 23152520
TI  - Critical role of MDA5 in the interferon response induced by human metapneumovirus
      infection in dendritic cells and in vivo.
AB  - Human metapneumovirus (hMPV) is a respiratory paramyxovirus of global clinical
      relevance. Despite the substantial knowledge generated during the last 10 years
      about hMPV infection, information regarding the activation of the immune response
      against this virus remains largely unknown. In this study, we demonstrated that
      the helicase melanoma differentiation-associated gene 5 (MDA5) is essential to
      induce the interferon response after hMPV infection in human and mouse dendritic
      cells as well as in an experimental mouse model of infection. Our findings in
      vitro and in vivo showed that MDA5 is required for the expression and activation
      of interferon (IFN) regulatory factors (IRFs). hMPV infection induces activation
      of IRF-3, and it regulates the expression of IRF-7. However, both IRF-3 and IRF-7
      are critical for the production of type I and type III IFNs. In addition, our in
      vivo studies in hMPV-infected mice indicated that MDA5 alters viral clearance,
      enhances disease severity and pulmonary inflammation, and regulates the
      production of cytokines and chemokines in response to hMPV. These findings are
      relevant for a better understanding of the pathogenesis of hMPV infection.

PMID- 23152518
TI  - Loss of a tyrosine-dependent trafficking motif in the simian immunodeficiency
      virus envelope cytoplasmic tail spares mucosal CD4 cells but does not prevent
      disease progression.
AB  - A hallmark of pathogenic simian immunodeficiency virus (SIV) and human
      immunodeficiency virus (HIV) infections is the rapid and near-complete depletion
      of mucosal CD4(+) T lymphocytes from the gastrointestinal tract. Loss of these
      cells and disruption of epithelial barrier function are associated with microbial
      translocation, which has been proposed to drive chronic systemic immune
      activation and disease progression. Here, we evaluate in rhesus macaques a novel
      attenuated variant of pathogenic SIVmac239, termed DeltaGY, which contains a
      deletion of a Tyr and a proximal Gly from a highly conserved YxxO trafficking
      motif in the envelope cytoplasmic tail. Compared to SIVmac239, DeltaGY
      established a comparable acute peak of viremia but only transiently infected
      lamina propria and caused little or no acute depletion of mucosal CD4(+) T cells
      and no detectable microbial translocation. Nonetheless, these animals developed T
      cell activation and declining peripheral blood CD4(+) T cells and ultimately
      progressed with clinical or pathological features of AIDS. DeltaGY-infected
      animals also showed no infection of macrophages or central nervous system tissues
      even in late-stage disease. Although the DeltaGY mutation persisted, novel
      mutations evolved, including the formation of new YxxO motifs in two of four
      animals. These findings indicate that disruption of this trafficking motif by the
      DeltaGY mutation leads to a striking alteration in anatomic distribution of virus
      with sparing of lamina propria and a lack of microbial translocation. Because
      these animals exhibited wild-type levels of acute viremia and immune activation,
      our findings indicate that these pathological events are dissociable and that
      immune activation unrelated to gut damage can be sufficient for the development
      of AIDS.

PMID- 23152521
TI  - Systematic identification of H274Y compensatory mutations in influenza A virus
      neuraminidase by high-throughput screening.
AB  - Compensatory mutations contribute to the appearance of the oseltamivir resistance
      substitution H274Y in the neuraminidase (NA) gene of H1N1 influenza viruses.
      Here, we describe a high-throughput screening method utilizing error-prone PCR
      and next-generation sequencing to comprehensively screen NA genes for H274Y
      compensatory mutations. We found four mutations that can either fully (R194G,
      E214D) or partially (L250P, F239Y) compensate for the fitness deficiency of the
      H274Y mutant. The compensatory effect of E214D is applicable in both seasonal
      influenza virus strain A/New Caledonia/20/1999 and 2009 pandemic swine influenza
      virus strain A/California/04/2009. The technique described here has the potential
      to profile a gene at the single-nucleotide level to comprehend the dynamics of
      mutation space and fitness and thus offers prediction power for emerging mutant
      species.

PMID- 23152522
TI  - Epstein-Barr virus LMP1 modulates lipid raft microdomains and the vimentin
      cytoskeleton for signal transduction and transformation.
AB  - The Epstein-Barr virus (EBV) is an important human pathogen that is associated
      with multiple cancers. The major oncoprotein of the virus, latent membrane
      protein 1 (LMP1), is essential for EBV B-cell immortalization and is sufficient
      to transform rodent fibroblasts. This viral transmembrane protein activates
      multiple cellular signaling pathways by engaging critical effector molecules and
      thus acts as a ligand-independent growth factor receptor. LMP1 is thought to
      signal from internal lipid raft containing membranes; however, the mechanisms
      through which these events occur remain largely unknown. Lipid rafts are
      microdomains within membranes that are rich in cholesterol and sphingolipids.
      Lipid rafts act as organization centers for biological processes, including
      signal transduction, protein trafficking, and pathogen entry and egress. In this
      study, the recruitment of key signaling components to lipid raft microdomains by
      LMP1 was analyzed. LMP1 increased the localization of phosphatidylinositol 3
      kinase (PI3K) and its activated downstream target, Akt, to lipid rafts. In
      addition, mass spectrometry analyses identified elevated vimentin in rafts
      isolated from LMP1 expressing NPC cells. Disruption of lipid rafts through
      cholesterol depletion inhibited PI3K localization to membranes and decreased both
      Akt and ERK activation. Reduction of vimentin levels or disruption of its
      organization also decreased LMP1-mediated Akt and ERK activation and inhibited
      transformation of rodent fibroblasts. These findings indicate that LMP1
      reorganizes membrane and cytoskeleton microdomains to modulate signal
      transduction.

PMID- 23152523
TI  - Role of transmembrane domains of hepatitis B virus small surface proteins in
      subviral-particle biogenesis.
AB  - The hepatitis B virus (HBV) surface proteins not only are incorporated into the
      virion envelope but in addition form subviral particles (SVP) consisting solely
      of surface proteins and lipids. Heterologous expression of the small HBV envelope
      protein S produces secreted spherical SVP 20 nm in diameter, with approximately
      100 S molecules per particle. The pathway leading from the initial S translation
      product as a multispanning transmembrane protein to the final SVP is largely
      unknown. To investigate the role of the four transmembrane domains (TM) of S in
      this process, we introduced mutations in these regions and characterized their
      effects on SVP formation in transfected Huh7 cells. We found that the insertion
      of one amino acid in the center of the alpha-helix of TM1 or the exchange of TM1
      with a heterologous TM blocked SVP release and SVP formation by coexpressed wild
      type S chains in a transdominant negative fashion. Surprisingly, this effect was
      partially neutralized when the mutations were expressed in the background of the
      HBV surface protein M, suggesting that mutations in TM1 could partially be
      complemented by the pre-S2 domain. The exchange of TM2 with heterologous TMs that
      form alpha-helices of the same lengths was also incompatible with SVP formation.
      However, these mutants no longer blocked SVP formation by coexpressed wild-type
      S. We conclude that TM2 is essential for the stable assembly of S chains by
      establishing intramembrane interactions.

PMID- 23152526
TI  - Trimeric glycosylphosphatidylinositol-anchored HCDR3 of broadly neutralizing
      antibody PG16 is a potent HIV-1 entry inhibitor.
AB  - PG9 and PG16 are two quaternary-structure-specific broadly neutralizing
      antibodies with unique HCDR3 subdomains. Previously, we showed that
      glycosylphosphatidylinositol (GPI)-anchored HCDR3 subdomains (GPI-HCDR3) can be
      targeted to lipid rafts of the plasma membrane, bind to the epitope recognized by
      HCDR3 of PG16, and neutralize diverse HIV-1 isolates. In this study, we further
      developed trimeric GPI-HCDR3s and demonstrated that trimeric GPI-HCDR3 (PG16)
      dramatically improves anti-HIV-1 neutralization, suggesting that a stoichiometry
      of recognition of 3 or 2 HCDR3 molecules (PG16) to 1 viral spike is possible.

PMID- 23152525
TI  - A vaccine based on the rhesus cytomegalovirus UL128 complex induces broadly
      neutralizing antibodies in rhesus macaques.
AB  - Neutralizing antibodies (NAb) are important for interfering with horizontal
      transmission of human cytomegalovirus (HCMV) leading to primary and congenital
      HCMV infection. Recent findings have shown that a pentameric virion complex
      formed by the glycoproteins gH/gL, UL128, UL130, and UL131A (UL128C) is required
      for HCMV entry into epithelial/endothelial cells (Epi/EC) and is the target of
      potent NAb in HCMV-seropositive individuals. Using bacterial artificial
      chromosome technology, we have generated a modified vaccinia Ankara virus (MVA)
      that stably coexpresses all 5 rhesus CMV (RhCMV) proteins homologous to HCMV
      UL128C, termed MVA-RhUL128C. Coimmunoprecipitation confirmed the interaction of
      RhgH with the other 4 RhCMV subunits of the pentameric complex. All 8 RhCMV-naive
      rhesus macaques (RM) vaccinated with MVA-RhUL128C developed NAb that blocked
      infection of monkey kidney epithelial cells (MKE) and rhesus fibroblasts. NAb
      titers induced by MVA-RhUL128C measured on both cell types at 2 to 6 weeks
      postvaccination were comparable to levels observed in naturally infected RM. In
      contrast, MVA expressing a subset of RhUL128C proteins or RhgB glycoprotein only
      minimally stimulated NAb that inhibited infection of MKE. In addition, following
      subcutaneous RhCMV challenge at 8 weeks postvaccination, animals vaccinated with
      MVA-RhUL128C showed reduced plasma viral loads. These results indicate that MVA
      expressing the RhUL128C induces NAb inhibiting RhCMV entry into both Epi/EC and
      fibroblasts and limits RhCMV replication in RM. This novel approach is the first
      step in developing a prophylactic HCMV vaccine designed to interfere with virus
      entry into major cell types permissive for viral replication, a required property
      of an effective vaccine.

PMID- 23152527
TI  - Cyclin T1 and CDK9 T-loop phosphorylation are downregulated during establishment
      of HIV-1 latency in primary resting memory CD4+ T cells.
AB  - P-TEFb, a cellular kinase composed of Cyclin T1 and CDK9, is essential for
      processive HIV-1 transcription. P-TEFb activity is dependent on phosphorylation
      of Thr186 in the CDK9 T loop. In resting CD4(+) T cells which are nonpermissive
      for HIV-1 replication, the levels of Cyclin T1 and T-loop-phosphorylated CDK9 are
      very low but increase significantly upon cellular activation. Little is known
      about how P-TEFb activity and expression are regulated in resting central memory
      CD4(+) T cells, one of the main reservoirs of latent HIV-1. We used an in vitro
      primary cell model of HIV-1 latency to show that P-TEFb availability in resting
      memory CD4(+) T cells is governed by the differential expression and
      phosphorylation of its subunits. This is in contrast to previous observations in
      dividing cells, where P-TEFb can be regulated by its sequestration in the 7SK RNP
      complex. We find that resting CD4(+) T cells, whether naive or memory and
      independent of their infection status, have low levels of Cyclin T1 and T-loop
      phosphorylated CDK9, which increase upon activation. We also show that the
      decrease in Cyclin T1 protein upon the acquisition of a memory phenotype is in
      part due to proteasome-mediated proteolysis and likely also to
      posttranscriptional downregulation by miR-150. We also found that HEXIM1 levels
      are very low in ex vivo- and in vitro-generated resting memory CD4(+) T cells,
      thus limiting the sequestration of P-TEFb in the 7SK RNP complex, indicating that
      this mechanism is unlikely to be a driver of viral latency in this cell type.

PMID- 23152528
TI  - Oligomeric properties of adeno-associated virus Rep68 reflect its
      multifunctionality.
AB  - The adeno-associated virus (AAV) encodes four regulatory proteins called Rep. The
      large AAV Rep proteins Rep68 and Rep78 are essential factors required in almost
      every step of the viral life cycle. Structurally, they share two domains: a
      modified version of the AAA(+) domain that characterizes the SF3 family of
      helicases and an N-terminal domain that binds DNA specifically. The combination
      of these two domains imparts extraordinary multifunctionality to work as
      initiators of DNA replication and regulators of transcription, in addition to
      their essential role during site-specific integration. Although most members of
      the SF3 family form hexameric rings in vitro, the oligomeric nature of Rep68 is
      unclear due to its propensity to aggregate in solution. We report here a
      comprehensive study to determine the oligomeric character of Rep68 using a
      combination of methods that includes sedimentation velocity ultracentrifugation,
      electron microscopy, and hydrodynamic modeling. We have determined that residue
      Cys151 induces Rep68 to aggregate in vitro. We show that Rep68 displays a
      concentration-dependent dynamic oligomeric behavior characterized by the presence
      of two populations: one with monomers and dimers in slow equilibrium and a second
      one consisting of a mixture of multiple-ring structures of seven and eight
      members. The presence of either ATP or ADP induces formation of larger complexes
      formed by the stacking of multiple rings. Taken together, our results support the
      idea of a Rep68 molecule that exhibits the flexible oligomeric behavior needed to
      perform the wide range of functions occurring during the AAV life cycle.

PMID- 23152529
TI  - Herpes simplex virus 2 (HSV-2) prevents dendritic cell maturation, induces
      apoptosis, and triggers release of proinflammatory cytokines: potential links to
      HSV-HIV synergy.
AB  - Herpes simplex virus 2 (HSV-2) may cause frequent recurrences, highlighting its
      ability to evade host defense. This study tested the hypothesis that HSV-2
      interferes with dendritic cell (DC) function as an escape mechanism, which may
      contribute to enhanced HIV replication in coinfected populations. Immature
      monocyte-derived human DCs were exposed to live or UV-inactivated HSV-2 or
      lipopolysaccharide. Little or no increase in the maturation marker CD83 was
      observed in response to HSV-2 and HSV-2 exposed DCs were impaired in their
      ability to present antigen (influenza) to T cells. Exposure to UV-inactivated
      virus stimulated a modest, but significant increase in CD83, suggesting that
      viral gene expression contributes to the block in DC maturation. The functional
      impairment of HSV-2-exposed DCs could be partially attributed to the induction of
      apoptosis. Live and inactivated HSV-2 triggered an increase in the number of
      early and late apoptotic cells in both the infected and bystander cell
      populations; apoptosis was associated with a decrease in cellular FLICE
      inhibitory protein (c-FLIP). Paradoxically, HSV-2 induced Akt phosphorylation,
      which typically promotes DC maturation and survival. Despite these aberrant
      responses, live and inactivated HSV-2 induced the release of cytokines into
      culture supernatants, which were sufficient to activate HIV-1 replication in
      latently infected U1 cells. Together, these findings suggest that in the presence
      of overt or subclinical HSV-2, the function of mucosal DCs would be impaired.
      These responses may allow HSV to escape immune surveillance but may also promote
      HIV infection and contribute to the epidemiological link between HIV and HSV.

PMID- 23152524
TI  - Hepatitis C virus variants with decreased sensitivity to direct-acting antivirals
      (DAAs) were rarely observed in DAA-naive patients prior to treatment.
AB  - The prevalence of naturally occurring hepatitis C virus (HCV) variants that are
      less sensitive to direct-acting antiviral (DAA) inhibitors has not been fully
      characterized. We used population sequence analysis to assess the frequency of
      such variants in plasma samples from 3,447 DAA-naive patients with genotype 1
      HCV. In general, HCV variants with lower-level resistance (3- to 25-fold
      increased 50% inhibitor concentration [IC(50)]) to telaprevir were observed as
      the dominant species in 0 to 3% of patients, depending on the specific variant,
      whereas higher-level resistant variants (>25-fold-increased IC(50)) were not
      observed. Specific variants resistant to NS5A inhibitors were predominant in up
      to 6% of patients. Most variants resistant to nucleo(s/t)ide active-site NS5B
      polymerase inhibitors were not observed, whereas variants resistant to non
      nucleoside allosteric inhibitors were observed in up to 18% of patients. The
      presence of DAA-resistant variants in NS5A, NS5B, or NS3 (including telaprevir
      resistant variants), in baseline samples of treatment-naive patients receiving a
      telaprevir-based regimen in phase 3 studies did not affect the sustained viral
      response (SVR). Treatment-naive patients with viral populations containing the
      telaprevir-resistant variants NS3 V36M, T54S, or R155K at baseline achieved a 74%
      SVR rate, whereas patients with no resistant variants detected prior to treatment
      achieved a 76% SVR rate. The effect of specific resistant variant frequency on
      response to various DAA treatments in different patient populations, including
      interferon nonresponders, should be further studied.

PMID- 23152530
TI  - Unusual features of vaccinia virus extracellular virion form neutralization
      resistance revealed in human antibody responses to the smallpox vaccine.
AB  - The extracellular virion form (EV) of vaccinia virus (VACV) is essential for
      viral pathogenesis and is difficult to neutralize with antibodies. Why this is
      the case and how the smallpox vaccine overcomes this challenge remain
      incompletely understood. We previously showed that high concentrations of anti-B5
      antibodies are insufficient to directly neutralize EV (M. R. Benhnia, et al., J.
      Virol. 83:1201-1215, 2009). This allowed for at least two possible
      interpretations: covering the EV surface is insufficient for neutralization, or
      there are insufficient copies of B5 to allow anti-B5 IgG to cover the whole
      surface of EV and another viral receptor protein remains active. We endeavored to
      test these possibilities, focusing on the antibody responses elicited by
      immunization against smallpox. We tested whether human monoclonal antibodies
      (MAbs) against the three major EV antigens, B5, A33, and A56, could individually
      or together neutralize EV. While anti-B5 or anti-A33 (but not anti-A56) MAbs of
      appropriate isotypes were capable of neutralizing EV in the presence of
      complement, a mixture of anti-B5, anti-A33, and anti-A56 MAbs was incapable of
      directly neutralizing EV, even at high concentrations. This remained true when
      neutralizing the IHD-J strain, which lacks a functional version of the fourth and
      final known EV surface protein, A34. These immunological data are consistent with
      the possibility that viral proteins may not be the active component of the EV
      surface for target cell binding and infectivity. We conclude that the protection
      afforded by the smallpox vaccine anti-EV response is predominantly mediated not
      by direct neutralization but by isotype-dependent effector functions, such as
      complement recruitment for antibodies targeting B5 and A33.

PMID- 23152531
TI  - Cyclophilin inhibitors block arterivirus replication by interfering with viral
      RNA synthesis.
AB  - Virus replication strongly depends on cellular factors, in particular, on host
      proteins. Here we report that the replication of the arteriviruses equine
      arteritis virus (EAV) and porcine reproductive and respiratory syndrome virus
      (PRRSV) is strongly affected by low-micromolar concentrations of cyclosporine A
      (CsA), an inhibitor of members of the cyclophilin (Cyp) family. In infected
      cells, the expression of a green fluorescent protein (GFP) reporter gene inserted
      into the PRRSV genome was inhibited with a half-maximal inhibitory concentration
      (IC(50)) of 5.2 MUM, whereas the GFP expression of an EAV-GFP reporter virus was
      inhibited with an IC(50) of 0.95 MUM. Debio-064, a CsA analog that lacks its
      undesirable immunosuppressive properties, inhibited EAV replication with an
      IC(50) that was 3-fold lower than that of CsA, whereas PRRSV-GFP replication was
      inhibited with an IC(50) similar to that of CsA. The addition of 4 MUM CsA after
      infection prevented viral RNA and protein synthesis in EAV-infected cells, and
      CsA treatment resulted in a 2.5- to 4-log-unit reduction of PRRSV or EAV
      infectious progeny. A complete block of EAV RNA synthesis was also observed in an
      in vitro assay using isolated viral replication structures. The small interfering
      RNA-mediated knockdown of Cyp family members revealed that EAV replication
      strongly depends on the expression of CypA but not CypB. Furthermore, upon
      fractionation of intracellular membranes in density gradients, CypA was found to
      cosediment with membranous EAV replication structures, which could be prevented
      by CsA treatment. This suggests that CypA is an essential component of the viral
      RNA-synthesizing machinery.

PMID- 23152532
TI  - Significant reductions in Gag-protease-mediated HIV-1 replication capacity during
      the course of the epidemic in Japan.
AB  - Human immunodeficiency virus type 1 (HIV-1) evolves rapidly in response to host
      immune selection pressures. As a result, the functional properties of HIV-1
      isolates from earlier in the epidemic may differ from those of isolates from
      later stages. However, few studies have investigated alterations in viral
      replication capacity (RC) over the epidemic. In the present study, we compare Gag
      Protease-associated RC between early and late isolates in Japan (1994 to 2009).
      HIV-1 subtype B sequences from 156 antiretroviral-naive Japanese with chronic
      asymptomatic infection were used to construct a chimeric NL4-3 strain encoding
      plasma-derived gag-protease. Viral replication capacity was examined by infecting
      a long terminal repeat-driven green fluorescent protein-reporter T cell line. We
      observed a reduction in the RC of chimeric NL4-3 over the epidemic, which
      remained significant after adjusting for the CD4(+) T cell count and plasma virus
      load. The same outcome was seen when limiting the analysis to a single large
      cluster of related sequences, indicating that our results are not due to shifts
      in the molecular epidemiology of the epidemic in Japan. Moreover, the change in
      RC was independent of genetic distance between patient-derived sequences and wild
      type NL4-3, thus ruling out potential temporal bias due to genetic similarity
      between patient and historic viral backbone sequences. Collectively, these data
      indicate that Gag-Protease-associated HIV-1 replication capacity has decreased
      over the epidemic in Japan. Larger studies from multiple geographical regions
      will be required to confirm this phenomenon.

PMID- 23152533
TI  - Multiple Gag domains contribute to selective recruitment of murine leukemia virus
      (MLV) Env to MLV virions.
AB  - Retroviruses, like all enveloped viruses, must incorporate viral glycoproteins to
      form infectious particles. Interactions between the glycoprotein cytoplasmic tail
      and the matrix domain of Gag are thought to direct recruitment of glycoproteins
      to native virions for many retroviruses. However, retroviruses can also
      incorporate glycoproteins from other viruses to form infectious virions known as
      pseudotyped particles. The glycoprotein murine leukemia virus (MLV) Env can
      readily form pseudotyped particles with many retroviruses, suggesting a generic
      mechanism for recruitment. Here, we sought to identify which components of Gag,
      particularly the matrix domain, contribute to recruitment of MLV Env into
      retroviral particles. Unexpectedly, we discovered that the matrix domain of HIV-1
      Gag is dispensable for generic recruitment, since it could be replaced with a
      nonviral membrane-binding domain without blocking active incorporation of MLV Env
      into HIV virions. However, MLV Env preferentially assembles with MLV virions.
      When MLV and HIV particles are produced from the same cell, MLV Env is packaged
      almost exclusively by MLV particles, thus preventing incorporation into HIV
      particles. Surprisingly, the matrix domain of MLV Gag is not required for this
      selectivity, since MLV Gag containing the matrix domain from HIV is still able to
      outcompete HIV particles for MLV Env. Although MLV Gag is sufficient for
      selective incorporation to occur, no single Gag domain dictates the selectivity.
      Our findings indicate that Env recruitment is more complex than previously
      believed and that Gag assembly/budding sites have fundamental properties that
      affect glycoprotein incorporation.

PMID- 23152534
TI  - Novel, potentially zoonotic paramyxoviruses from the African straw-colored fruit
      bat Eidolon helvum.
AB  - Bats carry a variety of paramyxoviruses that impact human and domestic animal
      health when spillover occurs. Recent studies have shown a great diversity of
      paramyxoviruses in an urban-roosting population of straw-colored fruit bats in
      Ghana. Here, we investigate this further through virus isolation and describe two
      novel rubulaviruses: Achimota virus 1 (AchPV1) and Achimota virus 2 (AchPV2). The
      viruses form a phylogenetic cluster with each other and other bat-derived
      rubulaviruses, such as Tuhoko viruses, Menangle virus, and Tioman virus. We
      developed AchPV1- and AchPV2-specific serological assays and found evidence of
      infection with both viruses in Eidolon helvum across sub-Saharan Africa and on
      islands in the Gulf of Guinea. Longitudinal sampling of E. helvum indicates virus
      persistence within fruit bat populations and suggests spread of AchPVs via
      horizontal transmission. We also detected possible serological evidence of human
      infection with AchPV2 in Ghana and Tanzania. It is likely that clinically
      significant zoonotic spillover of chiropteran paramyxoviruses could be missed
      throughout much of Africa where health surveillance and diagnostics are poor and
      comorbidities, such as infection with HIV or Plasmodium sp., are common.

PMID- 23152535
TI  - Alternative serotype adenovirus vaccine vectors elicit memory T cells with
      enhanced anamnestic capacity compared to Ad5 vectors.
AB  - The failure of the adenovirus serotype 5 (Ad5) vector-based human
      immunodeficiency virus type 1 (HIV-1) vaccine in the STEP study has led to the
      development of adenovirus vectors derived from alternative serotypes, such as
      Ad26, Ad35, and Ad48. We have recently demonstrated that vaccines using
      alternative-serotype Ad vectors confer partial protection against stringent
      simian immunodeficiency virus (SIV) challenges in rhesus monkeys. However,
      phenotypic differences between the T cell responses elicited by Ad5 and those of
      alternative-serotype Ad vectors remain unexplored. Here, we report the magnitude,
      phenotype, functionality, and recall capacity of memory T cell responses elicited
      in mice by Ad5, Ad26, Ad35, and Ad48 vectors expressing lymphocytic
      choriomeningitis virus (LCMV) glycoprotein (GP). Our data demonstrate that memory
      T cells elicited by Ad5 vectors were high in magnitude but exhibited functional
      exhaustion and decreased anamnestic potential following secondary antigen
      challenge compared to Ad26, Ad35, and Ad48 vectors. These data suggest that
      vaccination with alternative-serotype Ad vectors offers substantial immunological
      advantages over Ad5 vectors, in addition to circumventing high baseline Ad5
      specific neutralizing antibody titers.

PMID- 23152536
TI  - Expansion of monocytic myeloid-derived suppressor cells dampens T cell function
      in HIV-1-seropositive individuals.
AB  - T lymphocyte dysfunction contributes to human immunodeficiency virus type 1 (HIV
      1) disease progression by impairing antivirus cellular immunity. However, the
      mechanisms of HIV-1 infection-mediated T cell dysfunction are not completely
      understood. Here, we provide evidence that expansion of monocytic myeloid-derived
      suppressor cells (M-MDSCs) suppressed T cell function in HIV-1-infected
      individuals. We observed a dramatic elevation of M-MDSCs (HLA-DR(-/low) CD11b(+)
      CD33(+/high) CD14(+) CD15(-) cells) in the peripheral blood of HIV-1-seropositive
      subjects (n = 61) compared with healthy controls (n = 51), despite efficacious
      antiretroviral therapy for nearly 2 years. The elevated M-MDSC frequency in HIV
      1(+) subjects correlated with prognostic HIV-1 disease markers, including the HIV
      1 load (r = 0.5957; P < 0.0001), CD4(+) T cell loss (r = -0.5312; P < 0.0001),
      and activated T cells (r = 0.4421; P = 0.0004). Functional studies showed that M
      MDSCs from HIV-1(+) subjects suppressed T cell responses in both HIV-1-specific
      and antigen-nonspecific manners; this effect was dependent on the induction of
      arginase 1 and required direct cell-cell contact. Further investigations revealed
      that direct HIV-1 infection or culture with HIV-1-derived Tat protein
      significantly enhanced human MDSC generation in vitro, and MDSCs from healthy
      donors could be directly infected by HIV-1 to facilitate HIV-1 replication and
      transmission, indicating that a positive-feedback loop between HIV-1 infection
      and MDSC expansion existed. In summary, our studies revealed a novel mechanism of
      T cell dysfunction in HIV-1-infected individuals and suggested that targeting
      MDSCs may be a promising strategy for HIV-1 immunotherapy.

PMID- 23152537
TI  - Suppression of HIV-1 infection by APOBEC3 proteins in primary human CD4(+) T
      cells is associated with inhibition of processive reverse transcription as well
      as excessive cytidine deamination.
AB  - The Vif protein of human immunodeficiency virus type 1 (HIV-1) promotes viral
      replication by downregulation of the cell-encoded, antiviral APOBEC3 proteins.
      These proteins exert their suppressive effects through the inhibition of viral
      reverse transcription as well as the induction of cytidine deamination within
      nascent viral cDNA. Importantly, these two effects have not been characterized in
      detail in human CD4(+) T cells, leading to controversies over their possible
      contributions to viral inhibition in the natural cell targets of HIV-1
      replication. Here we use wild-type and Vif-deficient viruses derived from the
      CD4(+) T cells of multiple donors to examine the consequences of APOBEC3 protein
      function at natural levels of expression. We demonstrate that APOBEC3 proteins
      impart a profound deficiency to reverse transcription from the initial stages of
      cDNA synthesis, as well as excessive cytidine deamination (hypermutation) of the
      DNAs that are synthesized. Experiments using viruses from transfected cells and a
      novel method for mapping the 3' termini of cDNAs indicate that the inhibition of
      reverse transcription is not limited to a few specific sites, arguing that
      APOBEC3 proteins impede enzymatic processivity. Detailed analyses of mutation
      spectra in viral cDNA strongly imply that one particular APOBEC3 protein,
      APOBEC3G, provides the bulk of the antiviral phenotype in CD4(+) T cells, with
      the effects of APOBEC3F and APOBEC3D being less significant. Taken together, we
      conclude that the dual mechanisms of action of APOBEC3 proteins combine to
      deliver more effective restriction of HIV-1 than either function would by itself.

PMID- 23152538
TI  - Proteomic analysis reveals diverse classes of arginine methylproteins in
      mitochondria of trypanosomes.
AB  - Arginine (arg) methylation is a widespread posttranslational modification of
      proteins that impacts numerous cellular processes such as chromatin remodeling,
      RNA processing, DNA repair, and cell signaling. Known arg methylproteins arise
      mostly from yeast and mammals, and are almost exclusively nuclear and
      cytoplasmic. Trypanosoma brucei is an early branching eukaryote whose genome
      encodes five putative protein arg methyltransferases, and thus likely contains a
      plethora of arg methylproteins. Additionally, trypanosomes and related organisms
      possess a unique mitochondrion that undergoes dramatic developmental regulation
      and uses novel RNA editing and mitochondrial DNA replication mechanisms. Here, we
      performed a global mass spectrometric analysis of the T. brucei mitochondrion to
      identify new arg methylproteins in this medically relevant parasite. Enabling
      factors of this work are use of a combination digestion with two orthogonal
      enzymes, an efficient offline two dimensional chromatography separation, and high
      resolution mass spectrometry analysis with two complementary activations. This
      approach led to the comprehensive, sensitive and confident identification and
      localization of methylarg at a proteome level. We identified 167 arg
      methylproteins with wide-ranging functions including metabolism, transport,
      chaperoning, RNA processing, translation, and DNA replication. Our data suggest
      that arg methylproteins in trypanosome mitochondria possess both trypanosome
      specific and evolutionarily conserved modifications, depending on the protein
      targeted. This study is the first comprehensive analysis of mitochondrial arg
      methylation in any organism, and represents a significant advance in our
      knowledge of the range of arg methylproteins and their sites of modification.
      Moreover, these studies establish T. brucei as a model organism for the study of
      posttranslational modifications.

PMID- 23152539
TI  - Deep venomics reveals the mechanism for expanded peptide diversity in cone snail
      venom.
AB  - Cone snails produce highly complex venom comprising mostly small biologically
      active peptides known as conotoxins or conopeptides. Early estimates that
      suggested 50-200 venom peptides are produced per species have been recently
      increased at least 10-fold using advanced mass spectrometry. To uncover the
      mechanism(s) responsible for generating this impressive diversity, we used an
      integrated approach combining second-generation transcriptome sequencing with
      high sensitivity proteomics. From the venom gland transcriptome of Conus
      marmoreus, a total of 105 conopeptide precursor sequences from 13 gene
      superfamilies were identified. Over 60% of these precursors belonged to the three
      gene superfamilies O1, T, and M, consistent with their high levels of expression,
      which suggests these conotoxins play an important role in prey capture and/or
      defense. Seven gene superfamilies not previously identified in C. marmoreus,
      including five novel superfamilies, were also discovered. To confirm the
      expression of toxins identified at the transcript level, the injected venom of C.
      marmoreus was comprehensively analyzed by mass spectrometry, revealing 2710 and
      3172 peptides using MALDI and ESI-MS, respectively, and 6254 peptides using an
      ESI-MS TripleTOF 5600 instrument. All conopeptides derived from transcriptomic
      sequences could be matched to masses obtained on the TripleTOF within 100 ppm
      accuracy, with 66 (63%) providing MS/MS coverage that unambiguously confirmed
      these matches. Comprehensive integration of transcriptomic and proteomic data
      revealed for the first time that the vast majority of the conopeptide diversity
      arises from a more limited set of genes through a process of variable peptide
      processing, which generates conopeptides with alternative cleavage sites,
      heterogeneous post-translational modifications, and highly variable N- and C
      terminal truncations. Variable peptide processing is expected to contribute to
      the evolution of venoms, and explains how a limited set of ~ 100 gene transcripts
      can generate thousands of conopeptides in a single species of cone snail.

PMID- 23152540
TI  - SOX4 enables oncogenic survival signals in acute lymphoblastic leukemia.
AB  - The Sox4 transcription factor mediates early B-cell differentiation. Compared
      with normal pre-B cells, SOX4 promoter regions in Ph(+) ALL cells are
      significantly hypomethylated. Loss and gain-of-function experiments identified
      Sox4 as a critical activator of PI3K/AKT and MAPK signaling in ALL cells. ChIP
      experiments confirmed that SOX4 binds to and transcriptionally activates
      promoters of multiple components within the PI3K/AKT and MAPK signaling pathways.
      Cre-mediated deletion of Sox4 had little effect on normal pre-B cells but
      compromised proliferation and viability of leukemia cells, which was rescued by
      BCL2L1 and constitutively active AKT and p110 PI3K. Consistent with these
      findings, high levels of SOX4 expression in ALL cells at the time of diagnosis
      predicted poor outcome in a pediatric clinical trial (COG P9906). Collectively,
      these studies identify SOX4 as a central mediator of oncogenic PI3K/AKT and MAPK
      signaling in ALL.

PMID- 23152541
TI  - Early T-cell progenitors are the major granulocyte precursors in the adult mouse
      thymus.
AB  - The mouse thymus supports T-cell development, but also contains non-T-cell
      lineages such as dendritic cells, macrophages, and granulocytes that are
      necessary for T-cell repertoire selection and apoptotic thymocyte clearance.
      Early thymic progenitors (ETPs) are not committed to the T-cell lineage, as
      demonstrated by both in vitro and in vivo assays. Whether ETPs realize non-T-cell
      lineage potentials in vivo is not well understood and indeed is controversial. In
      the present study, we investigated whether ETPs are the major precursors of any
      non-T-lineage cells in the thymus. We analyzed the development of these
      populations under experimental circumstances in which ETPs are nearly absent due
      to either abrogated thymic settling or inhibition of early thymic development by
      genetic ablation of IL-7 receptoralpha or Hes1. Results obtained using multiple
      in vivo approaches indicate that the majority of thymic granulocytes derive from
      ETPs. These data indicate that myelolymphoid progenitors settle the thymus and
      thus clarify the pathways by which stem cells give rise to downstream blood cell
      lineages.

PMID- 23152542
TI  - The C-terminus of CBFbeta-SMMHC is required to induce embryonic hematopoietic
      defects and leukemogenesis.
AB  - The C-terminus of CBFbeta-SMMHC, the fusion protein produced by a chromosome 16
      inversion in acute myeloid leukemia subtype M4Eo, contains domains for self
      multimerization and transcriptional repression, both of which have been proposed
      to be important for leukemogenesis by CBFbeta-SMMHC. To test the role of the
      fusion protein's C-terminus in vivo, we generated knock-in mice expressing a C
      terminally truncated CBFbeta-SMMHC (CBFbeta-SMMHCDeltaC95). Embryos with a single
      copy of CBFbeta-SMMHCDeltaC95 were viable and showed no defects in hematopoiesis,
      whereas embryos homozygous for the CBFbeta-SMMHCDeltaC95 allele had hematopoietic
      defects and died in mid-gestation, similar to embryos with a single-copy of the
      full-length CBFbeta-SMMHC. Importantly, unlike mice expressing full-length
      CBFbeta-SMMHC, none of the mice expressing CBFbeta-SMMHCDeltaC95 developed
      leukemia, even after treatment with a mutagen, although some of the older mice
      developed a nontransplantable myeloproliferative disease. Our data indicate that
      the CBFbeta-SMMHC's C-terminus is essential to induce embryonic hematopoietic
      defects and leukemogenesis.

PMID- 23152543
TI  - CLEC5A is critical for dengue virus-induced inflammasome activation in human
      macrophages.
AB  - Persistent high fever is one of the most typical clinical symptoms in dengue
      virus (DV)-infected patients. However, the source of endogenous pyrogen (eg, IL
      1beta) and the signaling cascade leading to the activation of inflammasome and
      caspase-1, which are essential for IL-1beta and IL-18 secretion, during dengue
      infection have not been elucidated yet. Macrophages can be polarized into
      distinct phenotypes under the influence of GM-CSF or M-CSF, denoted as GM-Mphi
      and M-Mphi, respectively. We found that DV induced high levels of IL-1beta and IL
      18 from GM-Mphi (inflammatory macrophage) and caused cell death (pyroptosis),
      whereas M-Mphi (resting macrophage) did not produce IL-1beta and IL-18 on DV
      infection even with lipopolysaccharide priming. This observation demonstrates the
      distinct responses of GM-Mphi and M-Mphi to DV infection. Moreover, up-regulation
      of pro-IL-1beta, pro-IL-18, and NLRP3 associated with caspase-1 activation was
      observed in DV-infected GM-Mphi, whereas blockade of CLEC5A/MDL-1, a C-type
      lectin critical for dengue hemorrhagic fever and Japanese encephalitis virus
      infection, inhibits NLRP3 inflammasome activation and pyrotopsis in GM-Mphi.
      Thus, DV can activate NLRP3 inflammasome via CLEC5A, and GM-Mphi plays a more
      important role than M-Mphi in the pathogenesis of DV infection.

PMID- 23152544
TI  - DNA methylation changes are a late event in acute promyelocytic leukemia and
      coincide with loss of transcription factor binding.
AB  - The origin of aberrant DNA methylation in cancer remains largely unknown. In the
      present study, we elucidated the DNA methylome in primary acute promyelocytic
      leukemia (APL) and the role of promyelocytic leukemia-retinoic acid receptor
      alpha (PML-RARalpha) in establishing these patterns. Cells from APL patients
      showed increased genome-wide DNA methylation with higher variability than healthy
      CD34(+) cells, promyelocytes, and remission BM cells. A core set of
      differentially methylated regions in APL was identified. Age at diagnosis, Sanz
      score, and Flt3-mutation status characterized methylation subtypes. Transcription
      factor-binding sites (eg, the c-myc-binding sites) were associated with low
      methylation. However, SUZ12- and REST-binding sites identified in embryonic stem
      cells were preferentially DNA hypermethylated in APL cells. Unexpectedly, PML
      RARalpha-binding sites were also protected from aberrant DNA methylation in APL
      cells. Consistent with this, myeloid cells from preleukemic PML-RARalpha knock-in
      mice did not show altered DNA methylation and the expression of PML-RARalpha in
      hematopoietic progenitor cells prevented differentiation without affecting DNA
      methylation. Treatment of APL blasts with all-trans retinoic acid also did not
      result in immediate DNA methylation changes. The results of the present study
      suggest that aberrant DNA methylation is associated with leukemia phenotype but
      is not required for PML-RARalpha-mediated initiation of leukemogenesis.

PMID- 23152545
TI  - Immunotherapeutic strategies to prevent and treat human herpesvirus 6
      reactivation after allogeneic stem cell transplantation.
AB  - Human herpesvirus (HHV) 6 causes substantial morbidity and mortality in the
      immunocompromised host and has no approved therapy. Adoptive transfer of virus
      specific T cells has proven safe and apparently effective as prophylaxis and
      treatment of other virus infections in immunocompromised patients; however,
      extension to subjects with HHV6 has been hindered by the paucity of information
      on targets of cellular immunity. We now characterize the cellular immune response
      from 20 donors against 5 major HHV6B antigens predicted to be immunogenic and
      define a hierarchy of immunodominance of antigens based on the frequency of
      responding donors and the magnitude of the T-cell response. We identified
      specific epitopes within these antigens and expanded the HHV6 reactive T cells
      using a GMP-compliant protocol. The expanded population comprised both CD4(+) and
      CD8(+) T cells that were able to produce multiple effector cytokines and kill
      both peptide-loaded and HHV6B wild-type virus-infected target cells. Thus, we
      conclude that adoptive T-cell immunotherapy for HHV6 is a practical objective and
      that the peptide and epitope tools we describe will allow such cells to be
      prepared, administered, and monitored in human subjects.

PMID- 23152546
TI  - CCX-CKR deficiency alters thymic stroma impairing thymocyte development and
      promoting autoimmunity.
AB  - The atypical chemokine receptor CCX-CKR regulates bioavailability of CCL19,
      CCL21, and CCL25, homeostatic chemokines that play crucial roles in thymic
      lymphopoiesis. Deletion of CCX-CKR results in accelerated experimental
      autoimmunity induced by immunization. Here we show that CCX-CKR deletion also
      increases incidence of a spontaneous Sjogren's syndrome-like pathology,
      characterized by lymphocytic infiltrates in salivary glands and liver of CCX-CKR(
      /-) mice, suggestive of a defect in self-tolerance when CCX-CKR is deleted. This
      prompted detailed examination of the thymus in CCX-CKR(-/-) mice. Negatively
      selected mature SP cells were less abundant in CCX-CKR(-/-) thymi, yet expansion
      of both DP and immature SP cells was apparent. Deletion of CCX-CKR also
      profoundly reduced proportions of DN3 thymocyte precursors and caused DN2 cells
      to accumulate within the medulla. These effects are likely driven by alterations
      in thymic stroma as CCX-CKR(-/-) mice have fewer cTECs per thymocyte, and cTECs
      express the highest level of CCX-CKR in the thymus. A profound decrease in CCL25
      within the thymic cortex was observed in CCX-CKR(-/-) thymi, likely accounting
      for their defects in thymocyte distribution and frequency. These findings
      identify a novel role for CCX-CKR in regulating cTEC biology, which promotes
      optimal thymocyte development and selection important for self-tolerant adaptive
      immunity.

PMID- 23152547
TI  - Comparative evaluation of the Nanosphere Verigene RV+ assay and the Simplexa Flu
      A/B & RSV kit for detection of influenza and respiratory syncytial viruses.
AB  - Using retrospective (n = 200) and prospective (n = 150) nasopharyngeal specimens,
      we evaluated the Nanosphere Verigene RV+ and the Focus Diagnostics Simplexa Flu
      A/B & RSV tests. Overall, RV+ demonstrated sensitivities and specificities of
      96.6% and 100% for influenza A virus, 100% and 99.7% for influenza B virus, and
      100% and 100% for respiratory syncytial virus (RSV), while the Simplexa test
      sensitivities and specificities were 82.8 and 99.7%, 76.2 and 100%, and 94.6 and
      100%, respectively.

PMID- 23152548
TI  - Diagnostic accuracy and reproducibility of WHO-endorsed phenotypic drug
      susceptibility testing methods for first-line and second-line antituberculosis
      drugs.
AB  - In an effort to update and clarify policies on tuberculosis drug susceptibility
      testing (DST), the World Health Organization (WHO) commissioned a systematic
      review evaluating WHO-endorsed diagnostic tests. We report the results of this
      systematic review and meta-analysis of the diagnostic accuracy and
      reproducibility of phenotypic DST for first-line and second-line antituberculosis
      drugs. This review provides support for recommended critical concentrations for
      isoniazid and rifampin in commercial broth-based systems. Further studies are
      needed to evaluate critical concentrations for ethambutol and streptomycin that
      accurately detect susceptibility to these drugs. Evidence is limited on the
      performance of DST for pyrazinamide and second-line drugs.

PMID- 23152549
TI  - Emergence of OXA-48 and OXA-181 carbapenemases among Enterobacteriaceae in South
      Africa and evidence of in vivo selection of colistin resistance as a consequence
      of selective decontamination of the gastrointestinal tract.
AB  - This study reports on the emergence of OXA-48-like carbapenemases among isolates
      of Enterobacteriaceae in South Africa. In addition, the emergence during therapy
      of a colistin-resistant OXA-181-producing Klebsiella pneumoniae isolate was
      documented following selective digestive tract decontamination with oral
      colistin, which is therefore strongly discouraged.

PMID- 23152550
TI  - Comparison of broth enhancement to direct plating for screening of rectal
      cultures for ciprofloxacin-resistant Escherichia coli.
AB  - A transrectal prostate biopsy is the most common procedure used to establish the
      diagnosis of prostate cancer. Prior to biopsy, patients are commonly given
      ciprofloxacin for prophylaxis. However, a complication of the procedure is
      infection with ciprofloxacin-resistant organisms, in particular resistant
      Escherichia coli. In order to identify patients carrying ciprofloxacin-resistant
      E. coli, so as to tailor their antibiotic prophylaxis, rectal swabs are screened
      using selective broth and/or solid medium. In our evaluation, we compared broth
      enrichment and direct plating techniques by using brain heart infusion broth and
      MacConkey agar containing 1 MUg/ml or 10 MUg/ml of ciprofloxacin. Of the 100
      patients included in the study, 20 were colonized with ciprofloxacin-resistant
      organisms, 19 of which were E. coli. There was no significant difference (P >
      0.1) between the culture methods or the ciprofloxacin concentrations in the
      medium when identifying patients with ciprofloxacin-resistant E. coli; however,
      broth enrichment using 1 MUg/ml ciprofloxacin was the most sensitive at 100%, but
      it was the least specific. Direct plating of rectal swabs onto MacConkey agar
      containing 10 MUg/ml of ciprofloxacin was 100% specific and missed only 1
      positive specimen, with a sensitivity of 94.7%; this method was the most cost
      effective. Therefore, direct plating of rectal swabs onto selective medium proved
      to be a sensitive and cost-effective approach in identifying patients colonized
      with ciprofloxacin-resistant E. coli.

PMID- 23152551
TI  - Performance evaluation of the new Roche cobas AmpliPrep/cobas TaqMan HCV test,
      version 2.0, for detection and quantification of hepatitis C virus RNA.
AB  - To evaluate the analytical performance and explore the clinical applicability of
      the new Roche cobas AmpliPrep/cobas TaqMan HCV test, v2.0 (CAP/CTM v2.0), a
      platform comparison was performed on panels and diagnostic samples with the Roche
      cobas AmpliPrep/cobas TaqMan HCV test (CAP/CTM v1.0), the Siemens Versant HCV RNA
      3.0 branched DNA (bDNA) test, the Abbott m2000 RealTime HCV assay (Realtime
      assay), and the Siemens Versant HCV transcription-mediated amplification (TMA)
      test (TMA assay). The analytical performance of the CAP/CTM v2.0 on WHO and
      Acrometrix panels and clinical specimens of patients infected with HCV genotype
      1, 2, 3, 4, 5, or 6 relative to that of the CAP/CTM v1.0 was significantly
      improved. In a qualitative comparison of the CAP/CTM v2.0 relative to the TMA
      assay on genotype 1 to 4 samples, the two tests proved to be almost equally
      sensitive. Response-guided therapy in one of five HCV genotype 4-infected
      patients previously tested with the CAP/CTM v1.0 would have significantly changed
      if tested with the CAP/CTM v2.0. In conclusion, the Roche CAP/CTM v2.0 has
      significantly better performance characteristics than the former CAP/CTM HCV v1.0
      and the bDNA assay and performance characteristics comparable to those of the
      Realtime assay.

PMID- 23152552
TI  - Diagnostic accuracy of the genotype MTBDRsl assay for rapid diagnosis of
      extensively drug-resistant tuberculosis in HIV-coinfected patients.
AB  - The Russian Federation is a high-tuberculosis (TB)-burden country with high rates
      of Mycobacterium tuberculosis multidrug resistance (MDR) and extensive drug
      resistance (XDR), especially in HIV-coinfected patients. Rapid and reliable
      diagnosis for detection of resistance to second-line drugs is vital for adequate
      patient management. We evaluated the performance of the GenoType MTBDRsl (Hain
      Lifescience GmbH, Nehren, Germany) assay on smear-positive sputum specimens
      obtained from 90 HIV-infected MDR TB patients from Russia. Test interpretability
      was over 98%. Specificity was over 86% for all drugs, while sensitivity varied,
      being the highest (71.4%) for capreomycin and lowest (9.4%) for kanamycin,
      probably due to the presence of mutations in the eis gene. The sensitivity of
      detection of XDR TB was 13.6%, increasing to 42.9% if kanamycin (not commonly
      used in Western Europe) was excluded. The assay is a highly specific screening
      tool for XDR detection in direct specimens from HIV-coinfected TB patients but
      cannot be used to rule out XDR TB.

PMID- 23152553
TI  - Detection of Campylobacter species and Arcobacter butzleri in stool samples by
      use of real-time multiplex PCR.
AB  - The presence of Campylobacter (or Campylobacter-like) species in stools from
      patients suspected of infectious gastroenteritis (n = 493) was investigated using
      real-time PCR for detection of Arcobacter butzleri (hsp60 gene), Campylobacter
      coli (ceuE gene), Campylobacter jejuni (mapA), five acknowledged pathogenic
      Campylobacter spp. (C16S_Lund assay), and the Campylobacter genus (C16S_LvI
      assay). In total, 71.4% of the samples were positive for Campylobacter DNA (n =
      352) by a Campylobacter genus-specific (C16S_LvI) assay. A total of 23 samples
      (4.7%) were positive in the C16S_Lund assay, used for detection of C. jejuni, C.
      coli, C. lari, C. upsaliensis, and C. hyointestinalis. Subsequent identification
      of these samples yielded detection frequencies (DF) of 4.1% (C. jejuni), 0.4% (C.
      coli), and 0.4% (C. upsaliensis). The DF of A. butzleri was 0.4%. Interestingly,
      sequencing of a subgroup (n = 46) of C16S_LvI PCR-positive samples resulted in a
      considerable number of Campylobacter concisus-positive samples (n = 20). PCR
      positive findings with the C16S_Lund and C. jejuni/C. coli-specific assays were
      associated with more serious clinical symptoms (diarrhea and blood). Threshold
      cycle (C(T)) values of C. jejuni/C. coli PCR-positive samples were comparable to
      those of the C16S_Lund PCR (P = 0.21). C(T) values for both assays were
      significantly lower than those of the C16S_LvI assay (P < 0.001 and P < 0.00001,
      respectively). In conclusion, this study demonstrated that in combination, the C.
      jejuni/C coli-specific assays and the C16S_Lund assay are both useful for routine
      screening purposes. Furthermore, the DF of the emerging pathogen C. concisus was
      at least similar to the DF of C. jejuni.

PMID- 23152554
TI  - Clinical spectrum of exophiala infections and a novel Exophiala species,
      Exophiala hongkongensis.
AB  - We characterized 12 Exophiala strains isolated from patients over a 15-year
      period to the species level using phenotypic tests and internal transcribed
      spacer (ITS) and Rpb1 sequencing and described the clinical spectrum of the 12
      patients. Eight patients had nail or skin infections, two had invasive
      infections, and two had colonization of the gastrointestinal tract. ITS and Rpb1
      sequencing showed that 11 of the 12 strains were known Exophiala species (E.
      oligosperma [n = 3], E. jeanselmei [n = 2], E. lecanii-corni [n = 2], E. bergeri
      [n = 1], E. cancerae [n = 1], E. dermatitidis [n = 1], and E. xenobiotica [n =
      1]), which included the first reported cases of onychomycosis caused by E.
      bergeri and E. oligosperma. The 12th strain (HKU32(T)), isolated from the nail
      clipping of the right big toe of a 68-year-old female patient with onychomycosis,
      possessed unique morphological characteristics distinct from other Exophiala
      species. It grew very slowly and had a velvety colony texture after 28 days,
      short conidiophores of the same olivaceous color as the supporting hyphae,
      numerous spores, and no chlamydospore-like cells. ITS, Rpb1, beta-tubulin, and
      beta-actin gene sequencing unambiguously showed that HKU32(T) was clustered with
      but formed branches distinct from other Exophiala species in phylogenetic trees.
      We propose the new species Exophiala hongkongensis to describe this novel fungus.

PMID- 23152555
TI  - Multilocus sequence typing of Candida tropicalis shows the presence of different
      clonal clusters and fluconazole susceptibility profiles in sequential isolates
      from candidemia patients in Sao Paulo, Brazil.
AB  - The profiles of 61 Candida tropicalis isolates from 43 patients (28 adults and 15
      children) diagnosed with candidemia at two teaching hospitals in Sao Paulo,
      Brazil, were characterized by multilocus sequence typing (MLST). For the 14
      patients who had bloodstream infections, 32 isolates were serially collected from
      their blood and/or catheters. Thirty-nine diploid sequence types (DSTs) were
      differentiated. According to the C. tropicalis MLST database
      (http://pubmlst.org/ctropicalis/), 36 DSTs and 23 genotypes identified from the
      61 isolates had not previously been described. This report represents the first
      study to characterize sequential isolates of C. tropicalis from candidemia cases
      in South America. Microvariation in a single gene was found in the sequential
      isolates from 7 patients. The main polymorphisms occurred in the alleles of the
      XYR1 gene, specifically at nucleotide positions 215, 242, and 344. Macrovariation
      in six gene fragments was detected in the isolates from 3 patients. eBURST
      analysis added two new groups to this study (groups 6 and 18). Additionally,
      susceptibility tests indicate that 3 isolates were resistant to fluconazole. No
      correlation was found between the DSTs and susceptibility to fluconazole and/or
      selective antifungal pressure. Two patients were sequentially infected with
      resistant and susceptible strains. MLST is an important tool for studying the
      genetic diversity of multiple/sequential isolates of patients with candidemia,
      allowing the comparison of our data with those from other regions of the world,
      as well as allowing an analysis of the genetic relationship among several clones
      in sequential isolates from the same or different candidemia patient sites (blood
      or catheter).

PMID- 23152556
TI  - Felid herpesvirus 1 as a causative agent of severe nonsuppurative
      meningoencephalitis in a domestic cat.
AB  - Felid herpesvirus 1 is an important respiratory pathogen of domestic cats. This
      report presents the first case of severe nonsuppurative meningoencephalitis
      caused by this virus in a cat.

PMID- 23152557
TI  - Type-specific detection of 30 oncogenic human papillomaviruses by genotyping both
      E6 and L1 genes.
AB  - Human papillomavirus (HPV) is the principal cause of invasive cervical cancer and
      benign genital lesions. There are currently 30 HPV types linked to cervical
      cancer. HPV infection also leads to other types of cancer. We developed a 61-plex
      analysis of these 30 HPV types by examining two genes, E6 and L1, using MassARRAY
      matrix-assisted laser desorption ionization-time of flight mass spectrometry
      (MALDI-TOF MS) (PCR-MS). Two hundred samples from homosexual males (HM) were
      screened by PCR-MS and MY09/MY11 primer set-mediated PCR (MY-PCR) followed by
      sequencing. One hundred thirty-five formalin-fixed, paraffin-embedded (FFPE)
      cervical cancer samples were also analyzed by PCR-MS, and results were compared
      to those of the commercially available GenoArray (GA) assay. One or more HPV
      types were identified in 64.5% (129/200) of the samples from HM. Comprising all
      30 HPV types, PCR-MS detected 51.9% (67/129) of samples with multiple HPV types,
      whereas MY-PCR detected only one single HPV type in these samples. All PCR-MS
      results were confirmed by MY-PCR. In the cervical cancer samples, PCR-MS and GA
      detected 97% (131/135) and 90.4% (122/135) of HPV-positive samples, respectively.
      PCR-MS and GA results were fully concordant for 122 positive and 4 negative
      samples. The sequencing results for the 9 samples that tested negative by GA were
      completely concordant with the positive PCR-MS results. Multiple HPV types were
      identified in 25.2% (34/135) and 55.6% (75/135) of the cervical cancer samples by
      GA and PCR-MS, respectively, and results were confirmed by sequencing. The new
      assay allows the genotyping of >1,000 samples per day. It provides a good
      alternative to current methods, especially for large-scale investigations of
      multiple HPV infections and degraded FFPE samples.

PMID- 23152559
TI  - Tumor-infiltrating monocytic myeloid-derived suppressor cells mediate CCR5
      dependent recruitment of regulatory T cells favoring tumor growth.
AB  - Myeloid-derived suppressor cells (MDSCs) represent a heterogeneous population of
      myeloid cells in cancer patients and tumor-bearing mice that potently inhibits T
      cell responses. During tumor progression, MDSCs accumulate in several organs,
      including the tumor tissue. So far, tumor-infiltrating MDSC subpopulations remain
      poorly explored. In this study, we performed global gene expression profiling of
      mouse tumor-infiltrating granulocytic and monocytic (MO-MDSC) subsets compared
      with MDSCs from peripheral blood. RMA-S lymphoma-infiltrating MO-MDSCs not only
      produced high levels of NO and arginase-1, but also greatly increased levels of
      chemokines comprising the CCR5 ligands CCL3, CCL4, and CCL5. MO-MDSCs isolated
      from B16 melanoma and from skin tumor-bearing ret transgenic mice also expressed
      high levels of CCL3, CCL4, and CCL5. Expression of CCR5 was preferentially
      detected on regulatory T cells (Tregs). Accordingly, tumor-infiltrating MO-MDSCs
      directly attracted high numbers of Tregs via CCR5 in vitro. Intratumoral
      injection of CCL4 or CCL5 increased tumor-infiltrating Tregs, and deficiency of
      CCR5 led to their profound decrease. Moreover, in CCR5-deficient mice, RMA-S and
      B16 tumor growth was delayed emphasizing the importance of CCR5 in the control of
      antitumor immune responses. Overall, our data demonstrate that chemokines
      secreted by tumor-infiltrating MO-MDSCs recruit high numbers of Tregs revealing a
      novel suppressive role of MDSCs with potential clinical implications for the
      development of cancer immunotherapies.

PMID- 23152558
TI  - Dynorphin--still an extraordinarily potent opioid peptide.
AB  - This issue of Molecular Pharmacology is dedicated to Dr. Avram Goldstein, the
      journal's founding editor and one of the leaders in the development of modern
      pharmacology. This article focuses on his contributions to the discovery of the
      dynorphins and evidence that members of this family of opioid peptides are
      endogenous agonists for the kappa opioid receptor. In his original publication
      describing the purification and sequencing of dynorphin A, Avram described this
      peptide as "extraordinarily potent" ("dyn" from the Greek, dynamis = power and
      "orphin" for endogenous morphine peptide). The name originally referred to its
      high affinity and great potency in the bioassay that was used to follow its
      activity during purification, but the name has come to have a second meaning:
      studies of its physiologic function in brain continue to provide powerful
      insights to the molecular mechanisms controlling mood disorders and drug
      addiction. During the 30 years since its discovery, we have learned that the
      dynorphin peptides are released in brain during stress exposure. After they are
      released, they activate kappa opioid receptors distributed throughout the brain
      and spinal cord, where they trigger cellular responses resulting in different
      stress responses: analgesia, dysphoria-like behaviors, anxiety-like responses,
      and increased addiction behaviors in experimental animals. Avram predicted that a
      detailed molecular analysis of opiate drug actions would someday lead to better
      treatments for drug addiction, and he would be gratified to know that subsequent
      studies enabled by his discovery of the dynorphins resulted in insights that hold
      great promise for new treatments for addiction and depressive disorders.

PMID- 23152560
TI  - Plasmablasts generated during repeated dengue infection are virus glycoprotein
      specific and bind to multiple virus serotypes.
AB  - Dengue virus immune protection is specific to the serotype encountered and is
      thought to persist throughout one's lifetime. Many serotype cross-reactive memory
      B cells isolated from humans with previous dengue infection are specific for the
      nonstructural and the prM structural viral proteins, and they can enhance
      infection in vitro. However, plasmablasts circulating in enormous numbers during
      acute secondary infection have not been studied. In this study, we analyzed
      single plasmablasts from two patients by sorting the cells for Ig sequence
      analysis and for recombinant expression of Abs. In contrast to memory B cells,
      most plasmablast-derived Abs bound to the structural E protein of dengue, and
      protection experiments in mice revealed that virus serotypes encountered during
      past infections were neutralized more efficiently than were the serotypes of the
      current infection. Together with genetic analyses, we show evidence that
      plasmablasts in dengue patients are a polyclonal pool of activated E protein
      specific memory B cells and that their specificity is not representative of the
      serum Abs secreted by long-lived plasma cells in the memory phase. These results
      contribute to the understanding of the phenomenon of original antigenic sin in
      dengue.

PMID- 23152562
TI  - Inhibitory receptor paired Ig-like receptor B is exploited by Staphylococcus
      aureus for virulence.
AB  - The innate immune system has developed to acquire a wide variety of pattern
      recognition receptors (PRRs) to identify potential pathogens, whereas pathogens
      have also developed to escape host innate immune responses. ITIM-bearing
      receptors are attractive targets for pathogens to attenuate immune responses
      against them; however, the in vivo role of the inhibitory PRRs in host-bacteria
      interactions remains unknown. We demonstrate in this article that Staphylococcus
      aureus, a major Gram-positive bacteria, exploits inhibitory PRR paired Ig-like
      receptor (PIR)-B on macrophages to suppress ERK1/2 and inflammasome activation,
      and subsequent IL-6 and IL-1beta secretion. Consequently, Pirb(-/-) mice infected
      with S. aureus showed enhanced inflammation and more effective bacterial
      clearance, resulting in resistance to the sepsis. Screening of S. aureus mutants
      identified lipoteichoic acid (LTA) as an essential bacterial cell wall component
      required for binding to PIR-B and modulating inflammatory responses. In vivo,
      however, an LTA-deficient S. aureus mutant was highly virulent and poorly
      recognized by macrophages in both wild-type and Pirb(-/-) mice, demonstrating
      that LTA recognition by PRRs other than PIR-B mediates effective bacterial
      elimination. These results provide direct evidence that bacteria exploit the
      inhibitory receptor for virulence, and host immune system counterbalances the
      infection.

PMID- 23152561
TI  - Developmentally regulated availability of RANKL and CD40 ligand reveals distinct
      mechanisms of fetal and adult cross-talk in the thymus medulla.
AB  - T cell tolerance in the thymus is a key step in shaping the developing T cell
      repertoire. Thymic medullary epithelial cells play multiple roles in this
      process, including negative selection of autoreactive thymocytes, influencing
      thymic dendritic cell positioning, and the generation of Foxp3(+) regulatory T
      cells. Previous studies show that medullary thymic epithelial cell (mTEC)
      development involves hemopoietic cross-talk, and numerous TNFR superfamily
      members have been implicated in this process. Whereas CD40 and RANK represent key
      examples, interplay between these receptors, and the individual cell types
      providing their ligands at both fetal and adult stages of thymus development,
      remain unclear. In this study, by analysis of the cellular sources of receptor
      activator for NF-kappaB ligand (RANKL) and CD40L during fetal and adult cross
      talk in the mouse, we show that the innate immune cell system drives initial
      fetal mTEC development via expression of RANKL, but not CD40L. In contrast, cross
      talk involving the adaptive immune system involves both RANKL and CD40L, with
      analysis of distinct subsets of intrathymic CD4(+) T cells revealing a
      differential contribution of CD40L by conventional, but not Foxp3(+) regulatory,
      T cells. We also provide evidence for a stepwise involvement of TNFRs in mTEC
      development, with CD40 upregulation induced by initial RANK signaling
      subsequently controlling proliferation within the mTEC compartment. Collectively,
      our findings show how multiple hemopoietic cell types regulate mTEC development
      through differential provision of RANKL/CD40L during ontogeny, revealing
      molecular differences in fetal and adult hemopoietic cross-talk. They also
      suggest a stepwise process of mTEC development, in which RANK is a master player
      in controlling the availability of other TNFR family members.

PMID- 23152563
TI  - Suppressors of cytokine signaling promote Fas-induced apoptosis through
      downregulation of NF-kappaB and mitochondrial Bfl-1 in leukemic T cells.
AB  - Suppressors of cytokine signaling (SOCS) are known as negative regulators of
      cytokine- and growth factor-induced signal transduction. Recently they have
      emerged as multifunctional proteins with regulatory roles in inflammation,
      autoimmunity, and cancer. We have recently reported that SOCS1 has antiapoptotic
      functions against the TNF-alpha- and the hydrogen peroxide-induced T cell
      apoptosis through the induction of thioredoxin, which protects protein tyrosine
      phosphatases and attenuates Jaks. In this study, we report that SOCS, on the
      contrary, promote death receptor Fas-mediated T cell apoptosis. The proapoptotic
      effect of SOCS1 was manifested with increases in Fas-induced caspase-8
      activation, truncated Bid production, and mitochondrial dysfunctions. Both
      caspase-8 inhibitor c-Flip and mitochondrial antiapoptotic factor Bfl-1 were
      significantly reduced by SOCS1. These proapoptotic responses were not associated
      with changes in Jak or p38/Jnk activities but were accompanied with
      downregulation of NF-kappaB and NF-kappaB-dependent reporter gene expression.
      Indeed, p65 degradation via ubiquitination was accelerated in SOCS1
      overexpressing cells, whereas it was attenuated in SOCS1 knockdown cells. With
      high NF-kappaB levels, the SOCS1-ablated cells displayed resistance against Fas
      induced apoptosis, which was abrogated upon siBfl-1 transfection. The results
      indicate that the suppression of NF-kappaB-dependent induction of prosurvival
      factors, such as Bfl-1 and c-Flip, may serve as a mechanism for SOCS action to
      promote Fas-mediated T cell apoptosis. SOCS3 exhibited a similar proapoptotic
      function. Because both SOCS1 and SOCS3 are induced upon TCR stimulation, SOCS
      would play a role in activation-induced cell death by sensitizing activated T
      cells toward Fas-mediated apoptosis to maintain T cell homeostasis.

PMID- 23152564
TI  - Systemic flagellin immunization stimulates mucosal CD103+ dendritic cells and
      drives Foxp3+ regulatory T cell and IgA responses in the mesenteric lymph node.
AB  - Mucosal immunity is poorly activated after systemic immunization with protein
      Ags. Nevertheless, induction of mucosal immunity in such a manner would be an
      attractive and simple way to overcome the intrinsic difficulties in delivering Ag
      to such sites. Flagellin from Salmonella enterica serovar Typhimurium (FliC) can
      impact markedly on host immunity, in part via its recognition by TLR5. In this
      study, we show that systemic immunization with soluble FliC (sFliC) drives
      distinct immune responses concurrently in the mesenteric lymph nodes (MLN) and
      the spleen after i.p. and s.c. immunization. In the MLN, but not the spleen,
      sFliC drives a TLR5-dependent recruitment of CD103(+) dendritic cells (DCs),
      which correlates with a diminution in CD103(+) DC numbers in the lamina propria.
      In the MLN, CD103(+) DCs carry Ag and are the major primers of endogenous and
      transgenic T cell priming. A key consequence of these interactions with CD103(+)
      DCs in the MLN is an increase in local regulatory T cell differentiation. In
      parallel, systemic sFliC immunization results in a pronounced switching of FliC
      specific B cells to IgA in the MLN but not elsewhere. Loss of TLR5 has more
      impact on MLN than splenic Ab responses, reflected in an ablation of IgA, but not
      IgG, serum Ab titers. Therefore, systemic sFliC immunization targets CD103(+) DCs
      and drives distinct mucosal T and B cell responses. This offers a potential
      "Trojan horse" approach to modulate mucosal immunity by systemically immunizing
      with sFliC.

PMID- 23152567
TI  - The legacy of the tobacco colossus Richard Doll.

PMID- 23152568
TI  - Sequential bilateral femoral fractures.

PMID- 23152565
TI  - An anti-nucleic acid antibody delivers antigen to the cross-presentation pathway
      in dendritic cells and potentiates therapeutic antitumor effects.
AB  - Cross-presentation is important for initiating CTL responses against tumors.
      Delivery of exogenous Ags to the cross-presentation pathway in dendritic cells
      (DCs), using a number of different carriers, has been attempted to further
      understand the mechanisms underlying cross-presentation and to develop
      therapeutic tumor vaccines. The present study reports a new antigenic carrier
      molecule: a single-chain V region fragment (scFv) of a nucleic acid-hydrolyzing
      Ab, 3D8. A fusion protein comprising 3D8 scFv and the CTL epitope OVA(250-264)
      (chicken OVA aa 250-264) was internalized by DC2.4 DCs and processed via a
      proteasome-dependent, brefeldin- and cycloheximide-sensitive, chloroquine- and
      primaquine-insensitive pathway, resulting in loading of the CTL epitope onto H
      2K(b). In vivo cross-presentation and cross-priming were efficient, even without
      adjuvant; injection of mice with 3D8 scFv-OVA(250-264) induced cross-presentation
      of the CTL epitope by draining lymph node CD11c(+) B7.1(+) MHC class II(high)
      DCs, elicited a CTL response, and suppressed the growth of tumors expressing the
      OVA epitope. This report shows that an anti-nucleic acid Ab is used to deliver
      exogenous Ag to the cross-presentation pathway and inhibit in vivo tumor growth.

PMID- 23152569
TI  - Uncertainties in baseline risk estimates and confidence in treatment effects.

PMID- 23152570
TI  - Commentary: Substandard medicines are the priority for neglected tropical
      diseases.

PMID- 23152566
TI  - Human prostate tumor antigen-specific CD8+ regulatory T cells are inhibited by
      CTLA-4 or IL-35 blockade.
AB  - Regulatory T cells play important roles in cancer development and progression by
      limiting the generation of innate and adaptive anti-tumor immunity. We
      hypothesized that in addition to natural CD4(+)CD25(+) regulatory T cells (Tregs)
      and myeloid-derived suppressor cells, tumor Ag-specific Tregs interfere with the
      detection of anti-tumor immunity after immunotherapy. Using samples from prostate
      cancer patients immunized with a DNA vaccine encoding prostatic acid phosphatase
      (PAP) and a trans-vivo delayed-type hypersensitivity (tvDTH) assay, we found that
      the detection of PAP-specific effector responses after immunization was prevented
      by the activity of PAP-specific regulatory cells. These regulatory cells were
      CD8(+)CTLA-4(+), and their suppression was relieved by blockade of CTLA-4, but
      not IL-10 or TGF-beta. Moreover, Ag-specific CD8(+) Tregs were detected prior to
      immunization in the absence of PAP-specific effector responses. These PAP
      specific CD8(+)CTLA-4(+) suppressor T cells expressed IL-35, which was decreased
      after blockade of CTLA-4, and inhibition of either CTLA-4 or IL-35 reversed PAP
      specific suppression of tvDTH response. PAP-specific CD8(+)CTLA-4(+) T cells also
      suppressed T cell proliferation in an IL-35-dependent, contact-independent
      fashion. Taken together, these findings suggest a novel population of CD8(+)CTLA
      4(+) IL-35-secreting tumor Ag-specific Tregs arise spontaneously in some prostate
      cancer patients, persist during immunization, and can prevent the detection of Ag
      specific effector responses by an IL-35-dependent mechanism.

PMID- 23152571
TI  - Liverpool care pathway: doctors have always aimed to ease distress in dying.

PMID- 23152572
TI  - Liverpool care pathway: doctors speak out.

PMID- 23152573
TI  - Is fasting necessary before lipid tests?

PMID- 23152574
TI  - US inpatients often receive too much acetaminophen.

PMID- 23152575
TI  - Using end of life care pathways for the last hours or days of life.

PMID- 23152576
TI  - Death becomes him.

PMID- 23152577
TI  - DNA sequencing helped to limit spread of MRSA in a neonatal unit.

PMID- 23152578
TI  - New blueprint puts dementia and better care at heart of NHS.

PMID- 23152579
TI  - Head of NHS praises GPs' plans for commissioning.

PMID- 23152580
TI  - Rules over civil servants leaving for jobs in private sector need to be
      strengthened, says Labour.

PMID- 23152581
TI  - Vestigial-like 3 is an inhibitor of adipocyte differentiation.
AB  - Adipose differentiation is a complex process controlled by a network of
      transcription factors and co-regulators. We compared the global gene expression
      patterns of adipogenic and nonadipogenic clones of 3T3-F442A preadipocytes and
      identified the transcriptional cofactor, vestigial-like 3 (Vgll3), as an
      inhibitor of adipogenesis. Vgll3 expression is down-regulated during terminal
      adipocyte differentiation in vitro and negatively correlates with weight and
      total fat mass in vivo. Furthermore, enforced Vgll3 expression inhibits the
      differentiation of preadipocytes in vitro, whereas shRNA-mediated knockdown of
      Vgll3 expression promotes differentiation. Expression of Vgll3 promoted the
      expression of genes associated with bone and chondrocyte formation, suggesting
      that Vgll3 participates in the decision of mesenchymal cells to proceed down the
      adipocyte, bone, or cartilage lineages. The elucidation of factors involved in
      specification of the adipocyte phenotype may aid in the identification of new
      strategies for the treatment of metabolic disease.

PMID- 23152583
TI  - Posttranslational regulation of thioredoxin-interacting protein.
AB  - Thioredoxin-interacting protein (Txnip) is a metabolic regulator, which modulates
      insulin sensitivity and likely plays a role in type 2 diabetes. We studied the
      regulation of Txnip in 3T3-L1 adipocytes. Cells were incubated under different
      conditions and Txnip was measured by immunoblotting. We confirmed that high
      glucose markedly increases Txnip expression by promoting transcription. Insulin
      decreases Txnip protein levels. Rapamycin under most conditions decreased Txnip,
      suggesting that mTOR complex-1 is involved. The acute effects of insulin are
      mainly posttranscriptional; insulin (100  nM) accelerates Txnip degradation more
      than tenfold. This effect is cell type specific. It works in adipocytes,
      preadipocytes and in L6 myotubes but not in HepG2 or in HEK 293 cells or in a
      pancreatic beta-cell line. The ubiquitin/proteasome pathway is involved.
      Degradation of Txnip occurred within 15  min in the presence of 3  nM insulin and
      overnight with 0.6  nM insulin. Proteasomal Txnip degradation is not mediated by
      a cysteine protease or an anti-calpain enzyme. Okadaic acid (OKA), an inhibitor
      of phosphoprotein phosphatases (pp), markedly reduced Txnip protein and
      stimulated its further decrease by insulin. The latter occurred after incubation
      with 1 or 1000  nM OKA, suggesting that insulin enhances the phosphorylation of a
      pp2A substrate. Incubation with 0.1  MUM Wortmannin, a PI3 kinase inhibitor,
      increased Txnip protein twofold and significantly inhibited its insulin-induced
      decrease. Thus, while OKA mimics the effect of insulin, Wortmannin opposes it. In
      summary, insulin stimulates Txnip degradation by a PI3 kinase-dependent
      mechanism, which activates the ubiquitin/proteasome pathway and likely serves to
      mitigate insulin resistance.

PMID- 23152584
TI  - New immunohistochemical method for improved myotonia and chloride channel
      mutation diagnostics.
AB  - OBJECTIVE: The objective of this study was to validate the immunohistochemical
      assay for the diagnosis of nondystrophic myotonia and to provide full
      clarification of clinical disease to patients in whom basic genetic testing has
      failed to do so. METHODS: An immunohistochemical assay of sarcolemmal chloride
      channel abundance using 2 different ClC1-specific antibodies. RESULTS: This
      method led to the identification of new mutations, to the reclassification of
      W118G in CLCN1 as a moderately pathogenic mutation, and to confirmation of
      recessive (Becker) myotonia congenita in cases when only one recessive CLCN1
      mutation had been identified by genetic testing. CONCLUSIONS: We have developed a
      robust immunohistochemical assay that can detect loss of sarcolemmal ClC-1
      protein on muscle sections. This in combination with gene sequencing is a
      powerful approach to achieving a final diagnosis of nondystrophic myotonia.

PMID- 23152585
TI  - Surfers' myelopathy: a case series of 19 novice surfers with nontraumatic
      myelopathy.
AB  - OBJECTIVE: We report the clinical characteristics of the largest series of
      nontraumatic spinal cord injury in novice surfers (surfers' myelopathy). METHODS:
      A retrospective review of the electronic medical record was performed in patients
      with nontraumatic spinal cord injury associated with surfing identified upon
      admission to the largest tertiary referral hospital in Hawaii from June 2002 to
      November 2011. Classification by the American Spinal Injury Association
      Impairment Scale (AIS) was performed upon admission and at follow-up. Clinical
      management, including blood pressure measurements and optimization, use of
      corticosteroids, and diagnostic evaluations, were reviewed. Follow-up information
      was obtained by clinic visits, telephone interviews, and electronic mail up to 3
      years after injury. RESULTS: In 19 patients (14 male) aged 15-46 years, all
      patients complained of sudden onset of low back pain while surfing, followed by
      bilateral leg numbness and paralysis progressing over 10-60 minutes. All patients
      were novice surfers; 17 of 19 were surfing for the first time. On T2-weighted
      MRI, all patients had hyperintensity from the lower thoracic spinal cord to the
      conus medullaris. Six of 10 patients who underwent spinal diffusion-weighted MRI
      showed restricted diffusion in this region. Patients presenting with worse AIS
      scores had minimal improvement at follow-up. Blood pressure, corticosteroids, and
      imaging results were not associated with severity of neurologic deficits at
      follow-up. CONCLUSIONS: Although the cause of surfers' myelopathy is unclear, the
      rapid onset and presence of restricted diffusion suggest ischemic injury.
      Admission severity appears to be most predictive of neurologic outcome.

PMID- 23152582
TI  - Sphingolipids: regulators of crosstalk between apoptosis and autophagy.
AB  - Apoptosis and autophagy are two evolutionarily conserved processes that maintain
      homeostasis during stress. Although the two pathways utilize fundamentally
      distinct machinery, apoptosis and autophagy are highly interconnected and share
      many key regulators. The crosstalk between apoptosis and autophagy is complex, as
      autophagy can function to promote cell survival or cell death under various
      cellular conditions. The molecular mechanisms of crosstalk are beginning to be
      elucidated and have critical implications for the treatment of various diseases,
      such as cancer. Sphingolipids are a class of bioactive lipids that mediate many
      key cellular processes, including apoptosis and autophagy. By targeting several
      of the shared regulators, sphingolipid metabolites differentially regulate the
      induction of apoptosis and autophagy. Importantly, individual sphingolipid
      species appear to "switch" autophagy toward cell survival (e.g., sphingosine-1
      phosphate) or cell death (e.g., ceramide, gangliosides). This review assesses the
      current understanding of sphingolipid-induced apoptosis and autophagy to address
      how sphingolipids mediate the "switch" between the cell survival and cell death.
      As sphingolipid metabolism is frequently dysregulated in cancer, sphingolipid
      modulating agents, or sphingomimetics, have emerged as a novel chemotherapeutic
      strategy. Ultimately, a greater understanding of sphingolipid-mediated crosstalk
      between apoptosis and autophagy may be critical for enhancing the
      chemotherapeutic efficacy of these agents.

PMID- 23152586
TI  - Lewy pathology is not the first sign of degeneration in vulnerable neurons in
      Parkinson disease.
AB  - OBJECTIVE: To determine whether evidence of neuronal dysfunction or demise
      preceded deposition of Lewy pathology in vulnerable neurons in Parkinson disease
      (PD). METHODS: We examined the extent of nigral dysfunction and degeneration
      among 63 normal, incidental Lewy body disease (ILBD), and PD cases based on
      tyrosine hydroxylase (TH) immunoreactivity and neuron densities, respectively.
      The relationship between these markers and Lewy pathology (LP) burden in the
      substantia nigra (SN) and Braak PD stage was assessed. RESULTS: Compared with
      normal subjects, ILBD cases displayed a significantly higher percentage of TH
      negative cells and lower neuronal densities in the SN as early as Braak PD stages
      1 and 2, before LP deposition in the nigrostriatal system. ILBD nigral neuron
      densities were intermediate between normal subjects and PD cases, and TH-negative
      percentages were higher in ILBD than either normal or PD cases. Furthermore,
      neuron density and neuronal dysfunction levels remained relatively constant
      across Braak PD stages in ILBD. CONCLUSIONS: These results suggest that
      significant neurodegeneration and cellular dysfunction precede LP in the SN,
      challenging the pathogenic role of LP in PD and the assumption that ILBD always
      represents preclinical PD.

PMID- 23152588
TI  - Neurodegeneration in Parkinson disease: moving Lewy bodies out of focus.

PMID- 23152587
TI  - Novel mutation in VCP gene causes atypical amyotrophic lateral sclerosis.
AB  - OBJECTIVE: To identify the genetic variant that causes autosomal dominantly
      inherited motor neuron disease in a 4-generation Israeli-Arab family using
      genetic linkage and whole exome sequencing. METHODS: Genetic linkage analysis was
      performed in this family using Illumina single nucleotide polymorphism chips.
      Whole exome sequencing was then undertaken on DNA samples from 2 affected family
      members using an Illumina 2000 HiSeq platform in pursuit of potentially
      pathogenic genetic variants that comigrate with the disease in this pedigree.
      Variants meeting these criteria were then screened in all affected individuals.
      RESULTS: A novel mutation (p.R191G) in the valosin-containing protein (VCP) gene
      was identified in the index family. Direct sequencing of the VCP gene in a panel
      of DNA from 274 unrelated individuals with familial amyotrophic lateral sclerosis
      (FALS) revealed 5 additional mutations. Among them, 2 were previously identified
      in pedigrees with a constellation of inclusion body myopathy with Paget disease
      of the bone and frontotemporal dementia (IBMPFD) and in FALS, and 2 other
      mutations (p.R159C and p.R155C) in IBMPFD alone. We did not detect VCP gene
      mutations in DNA from 178 cases of sporadic amyotrophic lateral sclerosis.
      CONCLUSIONS: We report a novel VCP mutation identified in an amyotrophic lateral
      sclerosis family (p.R191G) with atypical clinical features. In our experience,
      VCP mutations arise in approximately 1.5% of FALS cases. Our study supports the
      view that motor neuron disease is part of the clinical spectrum of VCP-associated
      disease.

PMID- 23152589
TI  - Dexamethasone and long-term survival in bacterial meningitis.
AB  - BACKGROUND: Data on the long-term effect of dexamethasone on survival in
      bacterial meningitis are lacking. METHODS: A long-term follow-up study of the
      European Dexamethasone in Adulthood Bacterial Meningitis Study was performed. In
      this double-blind, randomized clinical trial, 301 patients were randomly assigned
      to receive adjunctive dexamethasone (n = 157) or placebo (n = 144) between June
      1993 and December 2001. We obtained survival data of patients using the Dutch
      Municipal Population Register. RESULTS: Death had occurred in 32 of 301 included
      patients (11%) at the primary outcome measurement 8 weeks after randomization.
      Follow-up was obtained for 228 of 246 evaluable patients (93%), with median
      follow-up of 13 years. Overall, 31 of 144 patients (22%) in the dexamethasone
      group died and 44 of 134 patients (33%) in the placebo group died (log-rank p =
      0.029). After the primary end point of the study at 8 weeks, 20 patients in the
      dexamethasone group died and 23 patients in the placebo group died (log-rank p =
      0.27), with age being the sole predictor of death (p < 0.001). CONCLUSIONS: In
      adults with community-acquired bacterial meningitis, the survival benefit from
      adjunctive dexamethasone therapy is obtained in the acute phase of the disease
      and remains for years. CLASSIFICATION OF EVIDENCE: This study of a population of
      Dutch patients shows Class III evidence that dexamethasone provides an extended
      survival benefit in patients treated for bacterial meningitis, and this survival
      benefit extends as long as 20 years.

PMID- 23152590
TI  - Prevention of mental disorders: a new era for workplace mental health.

PMID- 23152591
TI  - Proteasomal inhibition as a treatment strategy for Parkinson's disease: the
      impact of alpha-synuclein on Nurr1.

PMID- 23152592
TI  - Oxytocin modulates social distance between males and females.
AB  - In humans, interpersonal romantic attraction and the subsequent development of
      monogamous pair-bonds is substantially predicted by influential impressions
      formed during first encounters. The prosocial neuropeptide oxytocin (OXT) has
      been identified as a key facilitator of both interpersonal attraction and the
      formation of parental attachment. However, whether OXT contributes to the
      maintenance of monogamous bonds after they have been formed is unclear. In this
      randomized placebo-controlled trial, we provide the first behavioral evidence
      that the intranasal administration of OXT stimulates men in a monogamous
      relationship, but not single ones, to keep a much greater distance (~10-15 cm)
      between themselves and an attractive woman during a first encounter. This
      avoidance of close personal proximity occurred in the physical presence of female
      but not male experimenters and was independent of gaze direction and whether the
      female experimenter or the subject was moving. We further confirmed this
      unexpected finding using a photograph-based approach/avoidance task that showed
      again that OXT only stimulated men in a monogamous relationship to approach
      pictures of attractive women more slowly. Importantly, these changes cannot be
      attributed to OXT altering the attitude of monogamous men toward attractive women
      or their judgments of and arousal by pictures of them. Together, our results
      suggest that where OXT release is stimulated during a monogamous relationship, it
      may additionally promote its maintenance by making men avoid signaling romantic
      interest to other women through close-approach behavior during social encounters.
      In this way, OXT may help to promote fidelity within monogamous human
      relationships.

PMID- 23152593
TI  - Drosophila Psidin regulates olfactory neuron number and axon targeting through
      two distinct molecular mechanisms.
AB  - The formation of neuronal circuits is a key process of development, laying
      foundations for behavior. The cellular mechanisms regulating circuit development
      are not fully understood. Here, we reveal Psidin as an intracellular regulator of
      Drosophila olfactory system formation. We show that Psidin is required in several
      classes of olfactory receptor neurons (ORNs) for survival and subsequently for
      axon guidance. During axon guidance, Psidin functions as an actin regulator and
      antagonist of Tropomyosin. Accordingly, Psidin-deficient primary neurons in
      culture display growth cones with significantly smaller lamellipodia. This
      lamellipodial phenotype, as well as the mistargeting defects in vivo, is
      suppressed by parallel removal of Tropomyosin. In contrast, Psidin functions as
      the noncatalytic subunit of the N-acetyltransferase complex B (NatB) to maintain
      the number of ORNs. Psidin physically binds the catalytic NatB subunit CG14222
      (dNAA20) and functionally interacts with it in vivo. We define the dNAA20
      interaction domain within Psidin and identify a conserved serine as a candidate
      for phosphorylation-mediated regulation of NatB complex formation. A
      phosphomimetic mutation of this serine showed severely reduced binding to dNAA20
      in vitro. In vivo, it fully rescued the targeting defect but not the reduction in
      neuron numbers. In addition, we show that a different amino acid point mutation
      shows exactly the opposite effect by rescuing only the cell number but not the
      axon targeting defect. Together, our data suggest that Psidin plays two
      independent developmental roles via the acquisition of separate signaling
      pathways, both of which contribute to the formation of olfactory circuits.

PMID- 23152594
TI  - In vivo functional and myeloarchitectonic mapping of human primary auditory
      areas.
AB  - In contrast to vision, where retinotopic mapping alone can define areal borders,
      primary auditory areas such as A1 are best delineated by combining in vivo
      tonotopic mapping with postmortem cyto- or myeloarchitectonics from the same
      individual. We combined high-resolution (800 MUm) quantitative T(1) mapping with
      phase-encoded tonotopic methods to map primary auditory areas (A1 and R) within
      the "auditory core" of human volunteers. We first quantitatively characterize the
      highly myelinated auditory core in terms of shape, area, cortical depth profile,
      and position, with our data showing considerable correspondence to postmortem
      myeloarchitectonic studies, both in cross-participant averages and in
      individuals. The core region contains two "mirror-image" tonotopic maps oriented
      along the same axis as observed in macaque and owl monkey. We suggest that these
      two maps within the core are the human analogs of primate auditory areas A1 and
      R. The core occupies a much smaller portion of tonotopically organized cortex on
      the superior temporal plane and gyrus than is generally supposed. The multimodal
      approach to defining the auditory core will facilitate investigations of
      structure-function relationships, comparative neuroanatomical studies, and
      promises new biomarkers for diagnosis and clinical studies.

PMID- 23152595
TI  - Nociceptin/orphanin FQ receptor agonists attenuate L-DOPA-induced dyskinesias.
AB  - In the present study we investigated whether the neuropeptide nociceptin/orphanin
      FQ (N/OFQ), previously implicated in the pathogenesis of Parkinson's disease,
      also affects L-DOPA-induced dyskinesia. In striatal slices of naive rodents,
      N/OFQ (0.1-1 MUm) prevented the increase of ERK phosphorylation and the loss of
      depotentiation of synaptic plasticity induced by the D1 receptor agonist SKF38393
      in spiny neurons. In vivo, exogenous N/OFQ (0.03-1 nmol, i.c.v.) or a synthetic
      N/OFQ receptor agonist given systemically (0.01-1 mg/Kg) attenuated dyskinesias
      expression in 6-hydroxydopamine hemilesioned rats primed with L-DOPA, without
      causing primary hypolocomotive effects. Conversely, N/OFQ receptor antagonists
      worsened dyskinesia expression. In vivo microdialysis revealed that N/OFQ
      prevented dyskinesias simultaneously with its neurochemical correlates such as
      the surge of nigral GABA and glutamate, and the reduction of thalamic GABA.
      Regional microinjections revealed that N/OFQ attenuated dyskinesias more potently
      and effectively when microinjected in striatum than substantia nigra (SN)
      reticulata, whereas N/OFQ receptor antagonists were ineffective in striatum but
      worsened dyskinesias when given in SN. Quantitative autoradiography showed an
      increase in N/OFQ receptor binding in striatum and a reduction in SN of both
      unprimed and dyskinetic 6-hydroxydopamine rats, consistent with opposite adaptive
      changes of N/OFQ transmission. Finally, the N/OFQ receptor synthetic agonist also
      reduced dyskinesia expression in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine
      treated dyskinetic macaques without affecting the global parkinsonian score. We
      conclude that N/OFQ receptor agonists may represent a novel strategy to
      counteract L-DOPA-induced dyskinesias. Their action is possibly mediated by
      upregulated striatal N/OFQ receptors opposing the D1 receptor-mediated
      overactivation of the striatonigral direct pathway.

PMID- 23152596
TI  - Morphine withdrawal enhances constitutive MU-opioid receptor activity in the
      ventral tegmental area.
AB  - MU-Opioid receptors (MORs) in the ventral tegmental area (VTA) are pivotally
      involved in addictive behavior. While MORs are typically activated by opioids,
      they can also become constitutively active in the absence of any agonist. In the
      current study, we present evidence that MOR constitutive activity is highly
      relevant in the mouse VTA, as it regulates GABAergic input to dopamine neurons.
      Specifically, suppression of MOR constitutive activity with the inverse agonist
      KC-2-009 enhanced GABAergic neurotransmission onto VTA dopamine neurons. This
      inverse agonistic effect was fully blocked by the specific MOR neutral antagonist
      CTOP, which had no effect on GABAergic transmission itself. We next show that
      withdrawal from chronic morphine further increases the magnitude of inverse
      agonistic effects at the MOR, suggesting enhanced MOR constitutive activity. We
      demonstrate that this increase can be an adaptive response to the detrimental
      elevation in cAMP levels known to occur during morphine withdrawal. These
      findings offer important insights in the physiological occurrence and function of
      MOR constitutive activity, and have important implications for therapeutic
      strategies aimed at normalizing MOR signaling during addiction and opioid
      overdose.

PMID- 23152597
TI  - Targeting astrocytes ameliorates neurologic changes in a mouse model of
      Alzheimer's disease.
AB  - Astrocytes are the most abundant cell type in the brain and play a critical role
      in maintaining healthy nervous tissue. In Alzheimer's disease (AD) and most other
      neurodegenerative disorders, many astrocytes convert to a chronically "activated"
      phenotype characterized by morphologic and biochemical changes that appear to
      compromise protective properties and/or promote harmful neuroinflammatory
      processes. Activated astrocytes emerge early in the course of AD and become
      increasingly prominent as clinical and pathological symptoms progress, but few
      studies have tested the potential of astrocyte-targeted therapeutics in an intact
      animal model of AD. Here, we used adeno-associated virus (AAV) vectors containing
      the astrocyte-specific Gfa2 promoter to target hippocampal astrocytes in APP/PS1
      mice. AAV-Gfa2 vectors drove the expression of VIVIT, a peptide that interferes
      with the immune/inflammatory calcineurin/NFAT (nuclear factor of activated T
      cells) signaling pathway, shown by our laboratory and others to orchestrate
      biochemical cascades leading to astrocyte activation. After several months of
      treatment with Gfa2-VIVIT, APP/PS1 mice exhibited improved cognitive and synaptic
      function, reduced glial activation, and lower amyloid levels. The results confirm
      a deleterious role for activated astrocytes in AD and lay the groundwork for
      exploration of other novel astrocyte-based therapies.

PMID- 23152598
TI  - Diminished cortical inhibition in an aging mouse model of chronic tinnitus.
AB  - Flavoprotein autofluorescence imaging was used to examine auditory cortical
      synaptic responses in aged animals with behavioral evidence of tinnitus and
      hearing loss. Mice were exposed to noise trauma at 1-3 months of age and were
      assessed for behavioral evidence of tinnitus and hearing loss immediately after
      the noise trauma and again at ~24-30 months of age. Within 2 months of the final
      behavioral assessment, auditory cortical synaptic transmission was examined in
      brain slices using electrical stimulation of putative thalamocortical afferents,
      and flavoprotein autofluorescence imaging was used to measure cortical
      activation. Noise-exposed animals showed a 68% increase in amplitude of cortical
      activation compared with controls (p = 0.008), and these animals showed a
      diminished sensitivity to GABA(A)ergic blockade (p = 0.008, using bath-applied
      200 nm SR 95531 [6-Imino-3-(4-methoxyphenyl)-1(6H)-p yridazinebutanoic acid
      hydrobromide]). The strength of cortical activation was significantly correlated
      to the degree of tinnitus behavior, assessed via a loss of gap detection in a
      startle paradigm. The decrease in GABA(A) sensitivity was greater in the regions
      of the cortex farther away from the stimulation site, potentially reflecting a
      greater sensitivity of corticocortical versus thalamocortical projections to the
      effects of noise trauma. Finally, there was no relationship between auditory
      cortical activation and activation of the somatosensory cortex in the same
      slices, suggesting that the increases in auditory cortical activation were not
      attributable to a generalized hyperexcitable state in noise-exposed animals.
      These data suggest that noise trauma can cause long-lasting changes in the
      auditory cortical physiology and may provide specific targets to ameliorate the
      effects of chronic tinnitus.

PMID- 23152600
TI  - Left dorsal premotor cortex and supramarginal gyrus complement each other during
      rapid action reprogramming.
AB  - The ability to discard a prepared action plan in favor of an alternative action
      is critical when facing sudden environmental changes. We tested whether the
      functional contribution of left supramarginal gyrus (SMG) during action
      reprogramming depends on the functional integrity of left dorsal premotor cortex
      (PMd). Adopting a dual-site repetitive transcranial magnetic stimulation (rTMS)
      strategy, we first transiently disrupted PMd with "off-line" 1 Hz rTMS and then
      applied focal "on-line" rTMS to SMG while human subjects performed a spatially
      precued reaction time (RT) task. Effective on-line rTMS of SMG but not sham rTMS
      of SMG increased errors when subjects had to reprogram their action in response
      to an invalid precue regardless of the type of preceding off-line rTMS. This
      suggests that left SMG primarily contributes to the on-line updating of actions
      by suppressing invalidly prepared responses. On-line rTMS of SMG additionally
      increased RTs for correct responses in invalidly precued trials, but only after
      off-line rTMS of PMd. We infer that off-line rTMS caused an additional
      dysfunction of PMd, which increased the functional relevance of SMG for rapid
      activation of the correct response, and sensitized SMG to the disruptive effects
      of on-line rTMS. These results not only provide causal evidence that left PMd and
      SMG jointly contribute to action reprogramming, but also that the respective
      functional weight of these areas can be rapidly redistributed. This mechanism
      might constitute a generic feature of functional networks that allows for rapid
      functional compensation in response to focal dysfunctions.

PMID- 23152599
TI  - Dual-pitch processing mechanisms in primate auditory cortex.
AB  - Pitch, our perception of how high or low a sound is on a musical scale, is a
      fundamental perceptual attribute of sounds and is important for both music and
      speech. After more than a century of research, the exact mechanisms used by the
      auditory system to extract pitch are still being debated. Theoretically, pitch
      can be computed using either spectral or temporal acoustic features of a sound.
      We have investigated how cues derived from the temporal envelope and spectrum of
      an acoustic signal are used for pitch extraction in the common marmoset
      (Callithrix jacchus), a vocal primate species, by measuring pitch discrimination
      behaviorally and examining pitch-selective neuronal responses in auditory cortex.
      We find that pitch is extracted by marmosets using temporal envelope cues for
      lower pitch sounds composed of higher-order harmonics, whereas spectral cues are
      used for higher pitch sounds with lower-order harmonics. Our data support dual
      pitch processing mechanisms, originally proposed by psychophysicists based on
      human studies, whereby pitch is extracted using a combination of temporal
      envelope and spectral cues.

PMID- 23152601
TI  - Switching neuronal inputs by differential modulations of gamma-band phase
      coherence.
AB  - Receptive fields (RFs) of cortical sensory neurons increase in size along
      consecutive processing stages. When multiple stimuli are present in a large
      visual RF, a neuron typically responds to an attended stimulus as if only that
      stimulus were present. However, the mechanism by which a neuron selectively
      responds to a subset of its inputs while discarding all others is unknown. Here,
      we show that neurons can switch between subsets of their afferent inputs by
      highly specific modulations of interareal gamma-band phase-coherence (PC). We
      measured local field potentials, single- and multi-unit activity in two male
      macaque monkeys (Macaca mulatta) performing an attention task. Two small stimuli
      were placed on a screen; the stimuli were driving separate local V1 populations,
      while both were driving the same local V4 population. In each trial, we cued one
      of the two stimuli to be attended. We found that gamma-band PC of the local V4
      population with multiple subpopulations of its V1 input was differentially
      modulated. It was high with the input subpopulation representing the attended
      stimulus, while simultaneously it was very low between the same V4 population and
      the other input-providing subpopulation representing the irrelevant stimulus.
      These differential modulations, which depend on stimulus relevance, were also
      found in the locking of spikes from V4 neurons to the gamma-band oscillations of
      the V1 input subpopulations. This rapid, highly specific interareal locking
      provides neurons with a powerful dynamic routing mechanism to select and process
      only the currently relevant signals.

PMID- 23152602
TI  - beta-secretase cleavage of the fly amyloid precursor protein is required for
      glial survival.
AB  - beta-secretase (or BACE1) is the key enzyme in the production of beta-amyloid
      (Abeta), which accumulates in the senile plaques characteristic for Alzheimer's
      disease. Consequently, the lack of BACE1 prevents beta-processing of the amyloid
      precursor protein and Abeta production, which made it a promising target for drug
      development. However, the loss of BACE1 is also detrimental, leading to
      myelination defects and altered neuronal activity, functions that have been
      associated with the cleavage of Neuregulin and a voltage-gated sodium channel
      subunit. Here we show that the Drosophila ortholog of BACE, dBACE, is required
      for glial survival. Cell-specific knockdown experiments reveal that this is a non
      cell autonomous function, as a knockdown of dBACE in photoreceptor neurons leads
      to progressive degeneration of glia in their target zone, the lamina.
      Interestingly, this phenotype is suppressed by the loss of the fly amyloid
      precursor protein (APPL), whereas a secretion-deficient form of APPL enhances the
      degeneration. This shows that full-length APPL in neurons promotes the death of
      neighboring glial cells and that beta-processing of APPL is needed to prevent
      glial death. These results therefore not only demonstrate a novel function for an
      APP protein in glia, but they also show this function specifically requires
      regulation by beta-cleavage.

PMID- 23152604
TI  - In vivo imaging of disease-related mitochondrial dynamics in a vertebrate model
      system.
AB  - Mitochondria provide ATP, maintain calcium homeostasis, and regulate apoptosis.
      Neurons, due to their size and complex geometry, are particularly dependent on
      the proper functioning and distribution of mitochondria. Thus disruptions of
      these organelles and their transport play a central role in a broad range of
      neurodegenerative diseases. While in vitro studies have greatly expanded our
      knowledge of mitochondrial dynamics, our understanding in vivo remains limited.
      To address this shortcoming, we developed tools to study mitochondrial dynamics
      in vivo in optically accessible zebrafish. We demonstrate here that our newly
      generated tools, including transgenic "MitoFish," can be used to study the in
      vivo "life cycle" of mitochondria and allows identifying pharmacological and
      genetic modulators of mitochondrial dynamics. Furthermore we observed profound
      mitochondrial transport deficits in real time in a zebrafish tauopathy model. By
      rescuing this phenotype using MARK2 (microtubule-affinity regulating kinase 2),
      we provide direct in vivo evidence that this kinase regulates axonal transport in
      a Tau-dependent manner. Thus, our approach allows detailed studies of the
      dynamics of mitochondria in their natural environment under normal and disease
      conditions.

PMID- 23152603
TI  - Aging differentially affects the re-entrainment response of central and
      peripheral circadian oscillators.
AB  - Aging produces a decline in the amplitude and precision of 24 h behavioral,
      endocrine, and metabolic rhythms, which are regulated in mammals by a central
      circadian pacemaker within the suprachiasmatic nucleus (SCN) and local
      oscillators in peripheral tissues. Disruption of the circadian system, as
      experienced during transmeridian travel, can lead to adverse health consequences,
      particularly in the elderly. To test the hypothesis that age-related changes in
      the response to simulated jet lag will reflect altered circadian function, we
      examined re-entrainment of central and peripheral oscillators from young and old
      PER2::luciferase mice. As in previous studies, locomotor activity rhythms in
      older mice required more days to re-entrain following a shift than younger mice.
      At the tissue level, effects of age on baseline entrainment were evident, with
      older mice displaying earlier phases for the majority of peripheral oscillators
      studied and later phases for cells within most SCN subregions. Following a 6 h
      advance of the light:dark cycle, old mice displayed slower rates of re
      entrainment for peripheral tissues but a larger, more rapid SCN response compared
      to younger mice. Thus, aging alters the circadian timing system in a manner that
      differentially affects the re-entrainment responses of central and peripheral
      circadian clocks. This pattern of results suggests that a major consequence of
      aging is a decrease in pacemaker amplitude, which would slow re-entrainment of
      peripheral oscillators and reduce SCN resistance to external perturbation.

PMID- 23152605
TI  - Aneuploid cells are differentially susceptible to caspase-mediated death during
      embryonic cerebral cortical development.
AB  - Neural progenitor cells, neurons, and glia of the normal vertebrate brain are
      diversely aneuploid, forming mosaics of intermixed aneuploid and euploid cells.
      The functional significance of neural mosaic aneuploidy is not known; however,
      the generation of aneuploidy during embryonic neurogenesis, coincident with
      caspase-dependent programmed cell death (PCD), suggests that a cell's karyotype
      could influence its survival within the CNS. To address this hypothesis, PCD in
      the mouse embryonic cerebral cortex was attenuated by global pharmacological
      inhibition of caspases or genetic removal of caspase-3 or caspase-9. The
      chromosomal repertoire of individual brain cells was then assessed by chromosome
      counting, spectral karyotyping, fluorescence in situ hybridization, and DNA
      content flow cytometry. Reducing PCD resulted in markedly enhanced mosaicism that
      was comprised of increased numbers of cells with the following: (1) numerical
      aneuploidy (chromosome losses or gains); (2) extreme forms of numerical
      aneuploidy (>5 chromosomes lost or gained); and (3) rare karyotypes, including
      those with coincident chromosome loss and gain, or absence of both members of a
      chromosome pair (nullisomy). Interestingly, mildly aneuploid (<5 chromosomes lost
      or gained) populations remained comparatively unchanged. These data demonstrate
      functional non-equivalence of distinguishable aneuploidies on neural cell
      survival, providing evidence that somatically generated, cell-autonomous genomic
      alterations have consequences for neural development and possibly other brain
      functions.

PMID- 23152606
TI  - Parallel maturation of goal-directed behavior and dopaminergic systems during
      adolescence.
AB  - Adolescence is a crucial developmental period characterized by specific behaviors
      reflecting the immaturity of decision-making abilities. However, the maturation
      of precise cognitive processes and their neurobiological correlates at this
      period remain poorly understood. Here, we investigate whether a differential
      developmental time course of dopamine (DA) pathways during late adolescence could
      explain the emergence of particular executive and motivational components of goal
      directed behavior. First, using a contingency degradation protocol, we
      demonstrate that adolescent rats display a specific deficit when the causal
      relationship between their actions and their consequences is changed. When the
      rats become adults, this deficit disappears. In contrast, actions of adolescents
      remain sensitive to outcome devaluation or to the influence of a pavlovian
      conditioned stimulus. This aspect of cognitive maturation parallels a delayed
      development of the DA system, especially the mesocortical pathway involved in
      action adaptation to rule changes. Unlike in striatal and nucleus accumbens
      regions, DA fibers and DA tissue content continue to increase in the medial
      prefrontal cortex from juvenile to adult age. Moreover, a sustained
      overexpression of DA receptors is observed in the prefrontal region until the end
      of adolescence. These findings highlight the relationship between the emergence
      of specific cognitive processes, in particular the adaptation to changes in
      action consequences, and the delayed maturation of the mesocortical DA pathway.
      Similar developmental processes in humans could contribute to the adolescent
      vulnerability to the emergence of several psychiatric disorders characterized by
      decision-making deficits.

PMID- 23152607
TI  - Cognitive profile of amyloid burden and white matter hyperintensities in
      cognitively normal older adults.
AB  - Amyloid burden and white matter hyperintensities (WMH) are two common markers of
      neurodegeneration present in advanced aging. Each represents a potential early
      indicator of an age-related neurological disorder that impacts cognition. The
      presence of amyloid is observed in a substantial subset of cognitively normal
      older adults, but the literature remains equivocal regarding whether amyloid in
      nondemented populations is deleterious to cognition. Similarly, WMH are detected
      in many nondemented older adults and there is a body of evidence indicating that
      WMH are associated with decreased executive function and other cognitive domains.
      The current study investigated amyloid burden and WMH in clinically normal older
      adult humans aged 65-86 (N = 168) and examined each biomarker's relation with
      cognitive domains of episodic memory, executive function, and speed of
      processing. Factors for each domain were derived from a neuropsychological
      battery on a theoretical basis without reference to the relation between
      cognition and the biomarkers. Amyloid burden and WMH were not correlated with one
      another. Age was associated with lower performance in all cognitive domains,
      while higher estimated verbal intelligence was associated with higher performance
      in all domains. Hypothesis-driven tests revealed that amyloid burden and WMH had
      distinct cognitive profiles, with amyloid burden having a specific influence on
      episodic memory and WMH primarily associated with executive function but having
      broad (but lesser) effects on the other domains. These findings suggest that even
      before clinical impairment, amyloid burden and WMH likely represent
      neuropathological cascades with distinct etiologies and dissociable influences on
      cognition.

PMID- 23152608
TI  - The beta-secretase-derived C-terminal fragment of betaAPP, C99, but not Abeta, is
      a key contributor to early intraneuronal lesions in triple-transgenic mouse
      hippocampus.
AB  - Triple-transgenic mice (3xTgAD) overexpressing Swedish-mutated beta-amyloid
      precursor protein (betaAPP(swe)), P310L-Tau (Tau(P301L)), and physiological
      levels of M146V-presenilin-1 (PS1(M146V)) display extracellular amyloid-beta
      peptides (Abeta) deposits and Tau tangles. More disputed is the observation that
      these mice accumulate intraneuronal Abeta that has been linked to synaptic
      dysfunction and cognitive deficits. Here, we provide immunohistological, genetic,
      and pharmacological evidences for early, age-dependent, and hippocampus-specific
      accumulation of the beta-secretase-derived betaAPP fragment C99 that is observed
      from 3 months of age and enhanced by pharmacological blockade of gamma-secretase.
      Notably, intracellular Abeta is only detectable several months later and appears,
      as is the case of C99, in enlarged cathepsin B-positive structures, while
      extracellular Abeta deposits are detected ~12 months of age and beyond. Early C99
      production occurs mainly in the CA1/subicular interchange area of the hippocampus
      corresponding to the first region exhibiting plaques and tangles in old mice.
      Furthermore, the comparison of 3xTgAD mice with double-transgenic mice bearing
      the betaAPP(swe) and Tau(P301L) mutations but expressing endogenous PS1 (2xTgAD)
      demonstrate that C99 accumulation is not accounted for by a loss of function
      triggered by PS1 mutation that would have prevented C99 secondary cleavage by
      gamma-secretase. Together, our work identifies C99 as the earliest betaAPP
      catabolite and main contributor to the intracellular betaAPP-related
      immunoreactivity in 3xTgAD mice, suggesting its implication as an initiator of
      the neurodegenerative process and cognitive alterations taking place in this
      mouse model.

PMID- 23152610
TI  - Region-specific hierarchy between atrophy, hypometabolism, and beta-amyloid
      (Abeta) load in Alzheimer's disease dementia.
AB  - Gray matter atrophy, glucose hypometabolism, and beta-amyloid Abeta deposition
      are well-described hallmarks of Alzheimer's disease, but their relationships are
      poorly understood. The present study aims to compare the local levels of these
      three alterations in humans with Alzheimer's disease. Structural magnetic
      resonance imaging, (18)F-fluorodeoxyglucose positron emission tomography (PET),
      and (18)F-florbetapir PET data from 34 amyloid-negative healthy controls and 20
      demented patients with a high probability of Alzheimer's disease etiology
      (attested using neuroimaging biomarkers as recently recommended) were analyzed.
      For each patient and imaging modality, age-adjusted Z-score maps were computed,
      and direct between-modality voxelwise comparison and correlation analyses were
      performed. Significant differences in the levels of atrophy, hypometabolism, and
      Abeta deposition were found in most brain areas, but the hierarchy differed
      across regions. A cluster analysis revealed distinct subsets of regions: (1) in
      the hippocampus, atrophy exceeded hypometabolism, whereas Abeta load was minimal;
      (2) in posterior association areas, Abeta deposition was predominant, together
      with high hypometabolism and lower but still significant atrophy; and (3) in
      frontal regions, Abeta deposition was maximal, whereas structural and metabolic
      alterations were low. Atrophy and hypometabolism significantly correlated in the
      hippocampus and temporo-parietal cortex, whereas Abeta load was not significantly
      related to either atrophy or hypometabolism. These findings provide direct
      evidence for regional variations in the hierarchy and relationships between Abeta
      load, hypometabolism, and atrophy. Altogether, these variations probably reflect
      the differential involvement of region-specific pathological or protective
      mechanisms, such as the presence of neurofibrillary tangles, disconnection, as
      well as compensation processes.

PMID- 23152609
TI  - Efficient coding of spatial information in the primate retina.
AB  - Sensory neurons have been hypothesized to efficiently encode signals from the
      natural environment subject to resource constraints. The predictions of this
      efficient coding hypothesis regarding the spatial filtering properties of the
      visual system have been found consistent with human perception, but they have not
      been compared directly with neural responses. Here, we analyze the information
      that retinal ganglion cells transmit to the brain about the spatial information
      in natural images subject to three resource constraints: the number of retinal
      ganglion cells, their total response variances, and their total synaptic
      strengths. We derive a model that optimizes the transmitted information and
      compare it directly with measurements of complete functional connectivity between
      cone photoreceptors and the four major types of ganglion cells in the primate
      retina, obtained at single-cell resolution. We find that the ganglion cell
      population exhibited 80% efficiency in transmitting spatial information relative
      to the model. Both the retina and the model exhibited high redundancy (~30%)
      among ganglion cells of the same cell type. A novel and unique prediction of
      efficient coding, the relationships between projection patterns of individual
      cones to all ganglion cells, was consistent with the observed projection patterns
      in the retina. These results indicate a high level of efficiency with near
      optimal redundancy in visual signaling by the retina.

PMID- 23152611
TI  - Deficient use of visual information in estimating hand position in cerebellar
      patients.
AB  - We tested cerebellar degeneration in human patients in a task designed to isolate
      different aspects of motor planning and found a specific relationship between
      their ability to do inverse kinematic transformation and sparing of Crus I. Our
      approach was based on an experimental design introduced by Sober and Sabes (2003,
      2005). Their paradigm allows behavioral deficits in planning of movement
      direction to be dissociated from deficits in generation of motor commands and
      also allows for the relative role played by visual and proprioceptive information
      to be quantified. Perturbation of visual information about hand position affected
      cerebellar degeneration patients (N = 12) and age-matched controls equally in
      determining movement direction, but had less of an effect in both groups in the
      transformation of movement direction to motor command. However, when provided
      with vision of the joints, control participants were more affected in generating
      the motor command in perturbed trials, and cerebellar degeneration participants
      were not. Thus, cerebellar patients were less able to use visual information
      about the joints in generating motor commands. Voxel-based morphometric analysis
      showed that this inability was primarily correlated with degeneration of Crus I.
      These results show that the cerebellum plays a role in motor planning, and
      specifically in the generation of inverse kinematic models for sensorimotor
      processing. The involvement of Crus I is consistent with an emerging picture in
      which increasingly posterior lobules of the anterior cerebellar cortex are
      associated with increasingly complex and abstract aspects of motor behavior.

PMID- 23152613
TI  - Learning-related synaptic growth mediated by internalization of Aplysia cell
      adhesion molecule is controlled by membrane phosphatidylinositol 4,5-bisphosphate
      synthetic pathway.
AB  - Long-term facilitation in Aplysia is accompanied by the growth of new synaptic
      connections between the sensory and motor neurons of the gill-withdrawal reflex.
      One of the initial steps leading to the growth of these synapses is the
      internalization, induced by 5-HT, of the transmembrane isoform of Aplysia cell
      adhesion molecule (TM-apCAM) from the plasma membrane of sensory neurons (Bailey
      et al., 1992). However, the mechanisms that govern the internalization of TM
      apCAM and how this internalization is coupled to the molecular events that
      initiate the structural changes are not fully understood. Here, we report that
      the synthesis of membrane phosphatidylinositol 4,5-bisphosphate [PI(4,5)P(2)],
      which is known to be mediated by a signaling cascade through Aplysia Sec7 protein
      (ApSec7) and phosphatidylinositol-4-phosphate 5-kinase type I alpha (PIP5KIalpha)
      is required for both the internalization of TM-apCAM and the initiation of
      synaptic growth during 5-HT-induced long-term facilitation. Pharmacological
      blockade of PI(4,5)P(2) synthesis by the application of the inhibitor
      phenylarsine oxide blocked the internalization of apCAM. Furthermore,
      perturbation of the endogenous activation of ApSec7 and its downstream target
      PIP5KIalpha also blocked 5-HT-mediated internalization of TM-apCAM and synaptic
      growth. Finally, long-term facilitation was specifically impaired by blocking the
      ApSec7 signaling pathway at sensory-to-motor neuron synapses. These data indicate
      that the ApSec7/PIP5KIalpha signaling pathway is actively recruited during
      learning-related 5-HT signaling and acts as a key regulator of apCAM
      internalization associated with the formation of new synaptic connections during
      long-term facilitation.

PMID- 23152612
TI  - IRK-1 potassium channels mediate peptidergic inhibition of Caenorhabditis elegans
      serotonin neurons via a G(o) signaling pathway.
AB  - To identify molecular mechanisms that function in G-protein signaling, we have
      performed molecular genetic studies of a simple behavior of the nematode
      Caenorhabditis elegans, egg laying, which is driven by a pair of serotonergic
      neurons, the hermaphrodite-specific neurons (HSNs). The activity of the HSNs is
      regulated by the G(o)-coupled receptor EGL-6, which mediates inhibition of the
      HSNs by neuropeptides. We report here that this inhibition requires one of three
      inwardly rectifying K(+) channels encoded by the C. elegans genome: IRK-1. Using
      ChannelRhodopsin-2-mediated stimulation of HSNs, we observed roles for egl-6 and
      irk-1 in regulating the excitability of HSNs. Although irk-1 is required for
      inhibition of HSNs by EGL-6 signaling, we found that other G(o) signaling
      pathways that inhibit HSNs involve irk-1 little or not at all. These findings
      suggest that the neuropeptide receptor EGL-6 regulates the potassium channel IRK
      1 via a dedicated pool of G(o) not involved in other G(o)-mediated signaling. We
      conclude that G-protein-coupled receptors that signal through the same G-protein
      in the same cell might activate distinct effectors and that specific coupling of
      a G-protein-coupled receptor to its effectors can be determined by factors other
      than its associated G-proteins.

PMID- 23152614
TI  - Human immunodeficiency virus type 1 (HIV-1) transactivator of transcription
      through its intact core and cysteine-rich domains inhibits Wnt/beta-catenin
      signaling in astrocytes: relevance to HIV neuropathogenesis.
AB  - Wnt/beta-catenin is a neuroprotective pathway regulating cell fate commitment in
      the CNS and many vital functions of neurons and glia. Its dysregulation is linked
      to a number of neurodegenerative diseases. Wnt/beta-catenin is also a repressor
      of HIV transcription in multiple cell types, including astrocytes, which are
      dysregulated in HIV-associated neurocognitive disorder. Given that HIV proteins
      can overcome host restriction factors and that perturbations of Wnt/beta-catenin
      signaling can compromise astrocyte function, we evaluated the impact of HIV
      transactivator of transcription (Tat) on Wnt/beta-catenin signaling in
      astrocytes. HIV clade B Tat, in primary progenitor-derived astrocytes and U87MG
      cells, inhibited Wnt/beta-catenin signaling as demonstrated by its inhibition of
      active beta-catenin, TOPflash reporter activity, and Axin-2 (a downstream target
      of Wnt/beta-catenin signaling). Point mutations in either the core region (K41A)
      or the cysteine-rich region (C30G) of Tat abrogated its ability to inhibit beta
      catenin signaling. Clade C Tat, which lacks the dicysteine motif, did not alter
      beta-catenin signaling, confirming that the dicysteine motif is critical for Tat
      inhibition of beta-catenin signaling. Tat coprecipitated with TCF-4 (a
      transcription factor that partners with beta-catenin), suggesting a physical
      interaction between these two proteins. Furthermore, knockdown of beta-catenin or
      TCF-4 enhanced docking of Tat at the TAR region of the HIV long terminal repeat.
      These findings highlight a bidirectional interference between Tat and Wnt/beta
      catenin that negatively impacts their cognate target genes. The consequences of
      this interaction include alleviation of Wnt/beta-catenin-mediated suppression of
      HIV and possible astrocyte dysregulation contributing to HIV neuropathogenesis.

PMID- 23152615
TI  - Posthearing Ca(2+) currents and their roles in shaping the different modes of
      firing of spiral ganglion neurons.
AB  - Whereas prehearing spiral ganglion neurons (SGNs) rely faithfully on outputs from
      spontaneously active developing hair cells, the electrical phenotypes of
      posthearing neurons are shaped by distinct rapid and graded receptor potentials
      from hair cells. To date, technical difficulties in isolation of fragile
      posthearing neurons from the rigid bony labyrinth of the inner ear have hindered
      analyses of the electrical phenotype of SGNs. Therefore, we have recently
      developed new strategies to isolate posthearing mouse SGNs for functional
      analyses. Here, we describe the coarse and fine properties of Ca(2+) currents,
      which sculpt the firing properties of posthearing SGNs. Murine SGNs express
      multiple Ca(2+) channel currents to enable diverse functions. We have
      demonstrated that suppression of Ca(2+) currents results in significant
      hyperpolarization of the resting membrane potential (rmp) of basal SGNs,
      suggesting that Ca(2+) influx primes rmp for excitation. In contrast, removal of
      external Ca(2+) has modest effects on rmp of apical SGNs. The blockade of Ca(2+)
      currents with a mixture of specific blockers attenuates spontaneously active
      SGNs. Paradoxically, different subtypes of Ca(2+) currents, such as R-type
      currents, may activate resting outward conductances since blockage of the current
      results in depolarization of rmp. In keeping with whole-cell current data, single
      channel records revealed multiple diverse Ca(2+) channels in SGNs. Additionally,
      there were differential expressions of distinct Ca(2+) current densities in the
      apicobasal contour of the adult cochlea. This report provides invaluable insights
      into Ca(2+)-dependent processes in adult SGNs.

PMID- 23152616
TI  - Reduced gamma frequency in the medial frontal cortex of aged rats during behavior
      and rest: implications for age-related behavioral slowing.
AB  - Age-related cognitive and behavioral slowing may be caused by changes in the
      speed of neural signaling or by changes in the number of signaling steps
      necessary to achieve a given function. In the mammalian cortex, neural
      communication is organized by a 30-100 Hz "gamma" oscillation. There is a
      putative link between the gamma frequency and the speed of processing in a neural
      network: the dynamics of pyramidal neuron membrane time constants suggest that
      synaptic integration is framed by the gamma cycle, and pharmacological slowing of
      gamma also slows reaction times on behavioral tasks. The present experiments
      identify reductions in a robust 40-70 Hz gamma oscillation in the aged rat medial
      frontal cortex. The reductions were observed in the form of local field
      potentials, later peaks in fast-spiking neuron autocorrelations, and delays in
      the spiking of inhibitory neurons following local excitatory signals. Gamma
      frequency did not vary with movement speed, but rats with slower gamma also moved
      more slowly. Gamma frequency age differences were not observed in hippocampus.
      Hippocampal CA1 fast-spiking neurons exhibited interspike intervals consistent
      with a fast (70-100 Hz) gamma frequency, a pattern maintained across theta phases
      and theta frequencies independent of fluctuations in the average firing rates of
      the neurons. We propose that an average lengthening of the cortical 15-25 ms
      gamma cycle is one factor contributing to age-related slowing and that future
      attempts to offset cognitive declines will find a target in the response of fast
      spiking inhibitory neurons to excitatory inputs.

PMID- 23152617
TI  - Ca(V)1.3-driven SK channel activation regulates pacemaking and spike frequency
      adaptation in mouse chromaffin cells.
AB  - Mouse chromaffin cells (MCCs) fire spontaneous action potentials (APs) at rest.
      Ca(v)1.3 L-type calcium channels sustain the pacemaker current, and their loss
      results in depolarized resting potentials (V(rest)), spike broadening, and
      remarkable switches into depolarization block after BayK 8644 application. A
      functional coupling between Ca(v)1.3 and BK channels has been reported but cannot
      fully account for the aforementioned observations. Here, using Ca(v)1.3(-/-)
      mice, we investigated the role of Ca(v)1.3 on SK channel activation and how this
      functional coupling affects the firing patterns induced by sustained current
      injections. MCCs express SK1-3 channels whose tonic currents are responsible for
      the slow irregular firing observed at rest. Percentage of frequency increase
      induced by apamin was found inversely correlated to basal firing frequency. Upon
      stimulation, MCCs build-up Ca(v)1.3-dependent SK currents during the interspike
      intervals that lead to a notable degree of spike frequency adaptation (SFA). The
      major contribution of Ca(v)1.3 to the subthreshold Ca(2+) charge during an AP
      train rather than a specific molecular coupling to SK channels accounts for the
      reduced SFA of Ca(v)1.3(-/-) MCCs. Low adaptation ratios due to reduced SK
      activation associated with Ca(v)1.3 deficiency prevent the efficient recovery of
      Na(V) channels from inactivation. This promotes a rapid decline of AP amplitudes
      and facilitates early onset of depolarization block following prolonged
      stimulation. Thus, besides serving as pacemaker, Ca(v)1.3 slows down MCC firing
      by activating SK channels that maintain Na(V) channel availability high enough to
      preserve stable AP waveforms, even upon high-frequency stimulation of chromaffin
      cells during stress responses.

PMID- 23152618
TI  - Modulation of top-down control of visual attention by cathodal tDCS over right
      IPS.
AB  - The right intraparietal sulcus (rIPS) is a key region for the endogenous control
      of selective visual attention in the human brain. Previous studies suggest that
      the rIPS is especially involved in top-down control and spatial distribution of
      attention across both visual hemifields. We further explored these attentional
      functions using transcranial direct current stimulation (tDCS) of the rIPS to
      modulate behavioral performance in a partial report task. Performance was
      analyzed according to the theory of visual attention (TVA) (Bundesen, 1990),
      which provides a computational framework to investigate different parameters of
      visuo-attentional processing such as top-down control, attentional weighting,
      capacity of visual short term memory, and processing speed. We investigated the
      effects of different tDCS current strengths (1 mA and 2 mA) in two experiments: 1
      mA tDCS (anodal, cathodal, sham) did not affect any of the TVA parameters, but
      cathodal 2 mA stimulation significantly enhanced top-down control as evidenced by
      a reduction of the alpha parameter of TVA, regardless of hemifield. This
      differential impact on the top-down control component of attentional processing
      suggests that the horizontal rIPS is mainly involved in attentional selection as
      none of the spatial or resource variables of TVA were altered. Furthermore, the
      data add evidence to previous work highlighting (1) the importance of using
      appropriate current strength in stimulation protocols, and (2) that the often
      reported inhibitory effect of cathodal stimulation in e.g., motor tasks might not
      extend to cognitive paradigms.

PMID- 23152619
TI  - Fluoxetine (prozac) and serotonin act on excitatory synaptic transmission to
      suppress single layer 2/3 pyramidal neuron-triggered cell assemblies in the human
      prefrontal cortex.
AB  - Selective serotonin reuptake inhibitors are the most widely prescribed drugs
      targeting the CNS with acute and chronic effects in cognitive, emotional and
      behavioral processes. This suggests that microcircuits of the human cerebral
      cortex are powerfully modulated by selective serotonin reuptake inhibitors,
      however, direct measurements of serotonergic regulation on human synaptic
      interactions are missing. Using multiple whole-cell patch-clamp recordings from
      neurons in acute cortical slices derived from nonpathological human samples of
      the prefrontal cortex, we show that neuronal assemblies triggered by single
      action potentials of individual neurons in the human cortex are suppressed by
      therapeutic doses of fluoxetine (Prozac). This effect is boosted and can be
      mimicked by physiological concentrations of serotonin through 5HT-2A and 5HT-1A
      receptors. Monosynaptic excitatory connections from pyramidal cells to
      interneurons were suppressed by application of serotonin leaving the monosynaptic
      output of GABAergic cells unaffected. Changes in failure rate, in paired-pulse
      ratio, and in the coefficient of variation of the amplitude of EPSPs suggest a
      presynaptic action of serotonin. In conclusion, activation of neuronal
      assemblies, which were suggested as building blocks of high order cognitive
      processes, are effectively downregulated by the acute action of selective
      serotonin reuptake inhibitors or serotonin at the site of pyramidal output in
      human microcircuits.

PMID- 23152620
TI  - Attention selects informative neural populations in human V1.
AB  - In a neural population driven by a simple grating stimulus, different
      subpopulations are maximally informative about changes to the grating's
      orientation and contrast. In theory, observers should attend to the optimal
      subpopulation when switching between orientation and contrast discrimination
      tasks. Here we used source-imaged, steady-state visual evoked potentials and
      visual psychophysics to determine whether this is the case. Observers fixated
      centrally while static targets were presented bilaterally along with a cue
      indicating task type (contrast or orientation modulation detection) and task
      location (left or right). Changes in neuronal activity were measured by
      quantifying frequency-tagged responses from flickering "reporter" gratings
      surrounding the targets. To determine the orientation tuning of attentionally
      modulated neurons, we measured responses for three different probe-reporter
      angles: 0, 20, and 45 degrees . We estimated frequency-tagged cortical activity
      using a minimum norm inverse procedure combined with realistic MR-derived head
      models and retinotopically mapped visual areas. Estimates of neural activity from
      regions of interest centered on V1 showed that attention to a spatial location
      clearly increased the amplitude of the neural response in that location. More
      importantly, the pattern of modulation depended on the task. For orientation
      discrimination, attentional modulation showed a sharp peak in the population
      tuned 20 degrees  from the target orientation, whereas for contrast
      discrimination the enhancement was more broadly tuned. Similar tuning functions
      for orientation and contrast discrimination were obtained from psychophysical
      adaptation studies. These findings indicate that humans attend selectively to the
      most informative neural population and that these populations change depending on
      the nature of the task.

PMID- 23152621
TI  - PKC phosphorylation regulates mGluR5 trafficking by enhancing binding of Siah-1A.
AB  - Glutamate is the major excitatory neurotransmitter in the mammalian CNS and acts
      on both ionotropic and metabotropic glutamate receptors (mGluRs). The mGluRs are
      widely distributed in the CNS and modulate a variety of neuronal processes,
      including neurotransmitter release and ion channel function. In hippocampus and
      cortex, mGluR5 is highly expressed and plays an important role in the regulation
      of synaptic plasticity. Calmodulin (CaM) binding dynamically regulates mGluR5
      surface expression; however, the mechanisms linking CaM to mGluR5 trafficking are
      not clear. Recent studies showed that CaM binding to mGluR7 regulates its
      trafficking in a phosphorylation-dependent manner by disrupting the binding of
      protein interacting with C kinase 1. The E3 ligase seven in absentia homolog
      (Siah)-1A binds to mGluR5 and competes with CaM binding, making it an intriguing
      molecule to regulate phosphorylation-dependent trafficking of mGluR5. In the
      present study, we find that CaM competes with Siah-1A for mGluR5 binding in a
      phosphorylation-dependent manner in rat hippocampal neurons. Specifically,
      phosphorylation of mGluR5 S901 favors Siah-1A binding by displacing CaM. We
      identified critical residues regulating Siah-1A binding to mGluR5 and showed that
      binding is essential for the Siah-1A effects on mGluR5 trafficking. Siah-1A
      binding decreases mGluR5 surface expression and increases endosomal trafficking
      and lysosomal degradation of mGluR5. Thus CaM-regulated Siah-1A binding to mGluR5
      dynamically regulates mGluR5 trafficking. These findings support a conserved role
      for CaM in regulating mGluR trafficking by PKC-dependent regulation of receptor
      binding proteins.

PMID- 23152622
TI  - Reward stability determines the contribution of orbitofrontal cortex to adaptive
      behavior.
AB  - Animals respond to changing contingencies to maximize reward. The orbitofrontal
      cortex (OFC) is important for flexible responding when established contingencies
      change, but the underlying cognitive mechanisms are debated. We tested rats with
      sham or OFC lesions in radial maze tasks that varied the frequency of contingency
      changes and measured both perseverative and non-perseverative errors. When
      contingencies were changed rarely, rats with sham lesions learned quickly and
      performed better than rats with OFC lesions. Rats with sham lesions made fewer
      non-perseverative errors, rarely entering non-rewarded arms, and more win-stay
      responses by returning to recently rewarded arms compared with rats with OFC
      lesions. When contingencies were changed rapidly, however, rats with sham lesions
      learned slower, made more non-perseverative errors and fewer lose-shift
      responses, and returned more often to non-rewarded arms than rats with OFC
      lesions. The results support the view that the OFC integrates reward history and
      suggest that the availability of outcome expectancy signals can either improve or
      impair adaptive responding depending on reward stability.

PMID- 23152623
TI  - Physiological evidence consistent with reduced neuroplasticity in human
      adolescents born preterm.
AB  - Preterm-born children commonly experience motor, cognitive, and learning
      difficulties that may be accompanied by altered brain microstructure,
      connectivity, and neurochemistry. However, the mechanisms linking the altered
      neurophysiology with the behavioral outcomes are unknown. Here we provide the
      first physiological evidence that human adolescents born preterm at or before 37
      weeks of completed gestation have a significantly reduced capacity for cortical
      neuroplasticity, the key overall mechanism underlying learning and memory. We
      examined motor cortex neuroplasticity in three groups of adolescents who were
      born after gestations of <=32 completed weeks (early preterm), 33-37 weeks (late
      preterm), and 38-41 weeks (term) using a noninvasive transcranial magnetic brain
      stimulation technique to induce long-term depression (LTD)-like neuroplasticity.
      Compared with term-born adolescents, both early and late preterm adolescents had
      reduced LTD-like neuroplasticity in response to brain stimulation that was also
      associated with low salivary cortisol levels. We also compared neuroplasticity in
      term-born adolescents with that in term-born young adults, finding that the motor
      cortex retains a relatively enhanced neuroplastic capacity in adolescence. These
      findings provide a possible mechanistic link between the altered brain physiology
      of preterm birth and the subsequent associated behavioral deficits, particularly
      in learning and memory. They also suggest that altered hypothalamic-pituitary
      adrenal axis function due to preterm birth may be a significant modulator of this
      altered neuroplasticity. This latter finding may offer options in the development
      of possible therapeutic interventions.

PMID- 23152624
TI  - Action-specific value signals in reward-related regions of the human brain.
AB  - Estimating the value of potential actions is crucial for learning and adaptive
      behavior. We know little about how the human brain represents action-specific
      value outside of motor areas. This is, in part, due to a difficulty in detecting
      the neural correlates of value using conventional (region of interest) functional
      magnetic resonance imaging (fMRI) analyses, due to a potential distributed
      representation of value. We address this limitation by applying a recently
      developed multivariate decoding method to high-resolution fMRI data in subjects
      performing an instrumental learning task. We found evidence for action-specific
      value signals in circumscribed regions, specifically ventromedial prefrontal
      cortex, putamen, thalamus, and insula cortex. In contrast, action-independent
      value signals were more widely represented across a large set of brain areas.
      Using multivariate Bayesian model comparison, we formally tested whether value
      specific responses are spatially distributed or coherent. We found strong
      evidence that both action-specific and action-independent value signals are
      represented in a distributed fashion. Our results suggest that a surprisingly
      large number of classical reward-related areas contain distributed
      representations of action-specific values, representations that are likely to
      mediate between reward and adaptive behavior.

PMID- 23152625
TI  - Cell lineage analysis reveals three different progenitor pools for neurosensory
      elements in the otic vesicle.
AB  - In the inner ear, sensory versus neuronal specification is achieved through few
      well-defined bHLH transcription factors. However, the molecular mechanisms
      regulating the generation of the appropriate cell type in the correct place and
      at the correct time are not completely understood yet. Various studies have shown
      that hair cell- and neuron-specifying genes partially overlap in the otic
      territory, suggesting that mutual interactions among these bHLH factors could
      direct the generation of the two cell types from a common neurosensory
      progenitor. Although there is little evidence for a clonal relationship between
      macular hair cells and sensory neurons, the existence of a single progenitor able
      to give both sensory and neuronal cell types remains an open question. Here, we
      identified a population of common neurosensory progenitors in the zebrafish inner
      ear and studied the proneural requirement for cell fate decision within this
      population. Expression analysis reveals that proneural genes for hair cells and
      neurons overlap within the posteromedial otic epithelium. Combined results from
      single-cell lineage and functional studies on neurog1 and neuroD1 further
      demonstrate the following: (1) in the anterior region of the ear, neuronal and
      sensory lineages have already segregated at the onset of proneural gene
      expression and are committed to a given fate very early; (2) in contrast, the
      posteromedial part of the ear harbors a population of common progenitors giving
      both neurons and hair cells until late stages; and finally (3) neuroD1 is
      required within this pool of bipotent progenitors to generate the hair cell fate.

PMID- 23152626
TI  - Neural progenitor cells regulate capillary blood flow in the postnatal
      subventricular zone.
AB  - In the postnatal subventricular zone (SVZ), S phase entry of neural progenitor
      cells (NPCs) correlates with a local increase in blood flow. However, the
      cellular mechanism controlling this hemodynamic response remains unknown. We show
      that a subpopulation of SVZ cells, astrocyte-like cells or B-cells, sends
      projections ensheathing pericytes on SVZ capillaries in young mice. We examined
      whether calcium increases in pericytes or B-cells led to a vascular response in
      acute slices using the P2Y(2/4) receptor (P2Y(2/4)R) agonist UTP, electrical
      stimulation, or transgenic mice expressing exogenous Gq-coupled receptors (MrgA1)
      in B-cells. UTP increased calcium in pericytes leading to capillary
      constrictions. Electrical stimulation induced calcium propagation in SVZ cells
      followed by capillary constrictions involving purinergic receptors. In transgenic
      mice, selective calcium increases in B-cells induced P2Y(2/4)R-dependent
      capillary constrictions, suggesting that B-cells release ATP activating
      purinergic receptors on pericytes. Interestingly, in the presence of a P2Y(2/4)R
      blocker, dilation was observed. Intraventricular UTP injection transiently
      decreased blood flow monitored in vivo using laser Doppler flowmetry. Using
      neonatal electroporation, we expressed MrgA1 in slow cycling radial glia-derived
      B1 cells, i.e., NPCs. Intraventricular injection of an MrgA1 ligand increased
      blood flow in the SVZ. Thus, upon intracellular calcium increases B-cells/NPCs
      release ATP and vasodilating factors that activate purinergic receptors on
      pericytes triggering a vascular response and blood flow increase in vivo.
      Considering that NPCs receive signals from other SVZ cells, these findings
      further suggest that NPCs act as transducers of neurometabolic coupling in the
      SVZ.

PMID- 23152627
TI  - Anticipatory remapping of attentional priority across the entire visual field.
AB  - It has been suggested that one way we may create a stable percept of the visual
      world across multiple eye movements is to pass information from one set of
      neurons to another around the time of each eye movement. Previous studies have
      shown that some neurons in the lateral intraparietal area (LIP) exhibit
      anticipatory remapping: these neurons produce a visual response to a stimulus
      that will enter their receptive field after a saccade but before it actually does
      so. LIP responses during fixation are thought to represent attentional priority,
      behavioral relevance, or value. In this study, we test whether the remapped
      response represents this attentional priority by examining the activity of LIP
      neurons while animals perform a visual foraging task. We find that the population
      responds more to a target than to a distractor before the saccade even begins to
      bring the stimulus into the receptive field. Within 20 ms of the saccade ending,
      the responses in almost one-third of LIP neurons closely resemble the responses
      that will emerge during stable fixation. Finally, we show that, in these neurons
      and in the population as a whole, this remapping occurs for all stimuli in all
      locations across the visual field and for both long and short saccades. We
      conclude that this complete remapping of attentional priority across the visual
      field could underlie spatial stability across saccades.

PMID- 23152628
TI  - LRP1 in brain vascular smooth muscle cells mediates local clearance of
      Alzheimer's amyloid-beta.
AB  - Impaired clearance of amyloid-beta (Abeta) is a major pathogenic event for
      Alzheimer's disease (AD). Abeta depositions in brain parenchyma as senile plaques
      and along cerebrovasculature as cerebral amyloid angiopathy (CAA) are hallmarks
      of AD. A major pathway that mediates brain Abeta clearance is the cerebrovascular
      system where Abeta is eliminated through the blood-brain barrier (BBB) and/or
      degraded by cerebrovascular cells along the interstitial fluid drainage pathway.
      An Abeta clearance receptor, the low-density lipoprotein receptor-related protein
      1 (LRP1), is abundantly expressed in cerebrovasculature, in particular in
      vascular smooth muscle cells. Previous studies have indicated a role of LRP1 in
      endothelial cells in transcytosing Abeta out of the brain across the BBB;
      however, whether this represents a significant pathway for brain Abeta clearance
      remains controversial. Here, we demonstrate that Abeta can be cleared locally in
      the cerebrovasculature by an LRP1-dependent endocytic pathway in smooth muscle
      cells. The uptake and degradation of both endogenous and exogenous Abeta were
      significantly reduced in LRP1-suppressed human brain vascular smooth muscle
      cells. Conditional deletion of Lrp1 in vascular smooth muscle cell in amyloid
      model APP/PS1 mice accelerated brain Abeta accumulation and exacerbated Abeta
      deposition as amyloid plaques and CAA without affecting Abeta production. Our
      results demonstrate that LRP1 is a major Abeta clearance receptor in cerebral
      vascular smooth muscle cell and a disturbance of this pathway contributes to
      Abeta accumulation. These studies establish critical functions of the
      cerebrovasculature system in Abeta metabolism and identify a new pathway involved
      in the pathogenesis of both AD and CAA.

PMID- 23152629
TI  - Broadening of inhibitory tuning underlies contrast-dependent sharpening of
      orientation selectivity in mouse visual cortex.
AB  - Orientation selectivity (OS) in the visual cortex has been found to be invariant
      to increases in stimulus contrast, a finding that cannot be accounted for by the
      original, purely excitatory Hubel and Wiesel model. This property of OS may be
      important for preserving the quality of perceived stimulus across a range of
      stimulus intensity. The synaptic mechanisms that can prevent a broadening of OS
      caused by contrast-dependent strengthening of excitatory inputs to cortical
      neurons remain unknown. Using in vivo loose-patch recordings, we found in
      excitatory neurons in layer 4 of mouse primary visual cortex (V1) that the spike
      response to the preferred orientation was elevated as contrast increased while
      that to the orthogonal orientation remained unchanged, resulting in an overall
      sharpening rather than a weakening of OS. Whole-cell voltage-clamp recordings
      further revealed that contrast increases resulted in a scaling up of excitatory
      conductance at all stimulus orientations. Inhibitory conductance was enhanced at
      a similar level as excitation for the preferred orientation, but at a
      significantly higher level for the orthogonal orientation. Modeling revealed that
      the resulting broadening of inhibitory tuning is critical for maintaining and
      sharpening OS at high contrast. Finally, two-photon imaging guided recordings
      from parvalbumin-positive (PV) inhibitory neurons revealed that the broadening of
      inhibition can be attributed to a contrast-dependent broadening of spike-response
      tuning of PV neurons. Together our results suggest that modulation of synaptic
      inhibition in the mouse V1 cortical circuit preserves the sharpness of response
      selectivity during changes of stimulus strength.

PMID- 23152630
TI  - Mechanistic basis and functional roles of long-term plasticity in auditory
      neurons induced by a brain-generated estrogen.
AB  - The classic estrogen 17beta-estradiol (E2) was recently identified as a novel
      modulator of hearing function. It is produced rapidly, in an experience-dependent
      fashion, by auditory cortical neurons of both males and females. This brain
      generated E2 enhances the efficiency of auditory coding and improves the neural
      and behavioral discrimination of auditory cues. Remarkably, the effects of E2 are
      long-lasting and persist for hours after local rises in hormone levels have
      subsided. The mechanisms and functional consequences of this E2-induced
      plasticity of auditory responses are unknown. Here, we addressed these issues in
      the zebra finch model by combining intracerebral pharmacology, biochemical
      assays, in vivo neurophysiology in awake animals, and computational and
      information theoretical approaches. We show that auditory experience activates
      the MAPK pathway in an E2-dependent manner. This effect is mediated by estrogen
      receptor beta (ERbeta), which directly associates with MEKK1 to sequentially
      modulate MEK and ERK activation, where the latter is required for the engagement
      of downstream molecular targets. We further show that E2-mediated activation of
      the MAPK cascade is required for the long-lasting enhancement of auditory-evoked
      responses in the awake brain. Moreover, a functional consequence of this E2/MAPK
      activation is to sustain enhanced information handling and neural discrimination
      by auditory neurons for several hours following hormonal challenge. Our results
      demonstrate that brain-generated E2 engages, via a nongenomic interaction between
      an estrogen receptor and a kinase, a persistent form of experience-dependent
      plasticity that enhances the neural coding and discrimination of behaviorally
      relevant sensory signals in the adult vertebrate brain.

PMID- 23152631
TI  - Temporal dynamics of parvalbumin-expressing axo-axonic and basket cells in the
      rat medial prefrontal cortex in vivo.
AB  - Axo-axonic interneurons, innervating exclusively axon initial segments, and
      parvalbumin-expressing basket interneurons, targeting somata, dendrites, and
      spines of pyramidal cells, have been proposed to control neuronal activity in
      prefrontal circuits. We recorded the spike-timing of identified neurons in the
      prelimbic cortex of anesthetized rats, and show that axo-axonic cells increase
      their firing during tail pinch-induced brain state-activation. In addition, axo
      axonic cells differ from other GABAergic parvalbumin-expressing cells in their
      spike timing during DOWN- to UP-state transitions of slow oscillations and in
      their coupling to gamma and spindle oscillations. The distinct firing dynamics
      and synaptic targets of axo-axonic and other parvalbumin-expressing cells provide
      differential contributions to the temporal organization of prefrontal networks.

PMID- 23152632
TI  - Development and characterization of a new Parkinson's disease model resulting
      from impaired autophagy.
AB  - Parkinson's disease (PD) is a progressive neurodegenerative disease caused by the
      interaction of genetic and environmental factors. However, the etiology of PD
      remains largely unknown. Macroautophagy is known to play an essential role in the
      degradation of abnormal proteins and organelles. Furthermore, the loss of
      autophagy-related (Atg) genes results in neurodegeneration and abnormal protein
      accumulation. Since these are also pathologic features of Parkinson's disease,
      the conditional impairment of autophagy may lead to improved animal models for
      the study of PD. Using transgenic mice expressing Cre recombinase under the
      control of either the dopamine transporter or the engrailed-1 promoters, we
      generated mice with the conditional deletion of Atg7 in the dopamine neurons of
      the substantia nigra pars compacta, other regions of the midbrain, and also the
      hindbrain. This conditional impairment of autophagy results in the age-related
      loss of dopaminergic neurons and corresponding loss of striatal dopamine, the
      accumulation of low-molecular-weight alpha-synuclein, and the presence of
      ubiquitinated protein aggregates, recapitulating many of the pathologic features
      of PD. These conditional knock-out animals provide insight into the process of
      autophagy in Parkinson's disease pathology.

PMID- 23152633
TI  - Spinal atypical protein kinase C activity is necessary to stabilize inactivity
      induced phrenic motor facilitation.
AB  - The neural network controlling breathing must establish rhythmic motor output at
      a level adequate to sustain life. Reduced respiratory neural activity elicits a
      novel form of plasticity in circuits driving the diaphragm known as inactivity
      induced phrenic motor facilitation (iPMF), a rebound increase in phrenic
      inspiratory output observed once respiratory neural drive is restored. The
      mechanisms underlying iPMF are unknown. Here, we demonstrate in anesthetized rats
      that spinal mechanisms give rise to iPMF and that iPMF consists of at least two
      mechanistically distinct phases: (1) an early, labile phase that requires
      atypical PKC (PKCzeta and/or PKCiota/lambda) activity to transition to a (2)
      late, stable phase. Early (but not late) iPMF is associated with increased
      interactions between PKCzeta/iota and the scaffolding protein ZIP (PKCzeta
      interacting protein)/p62 in spinal regions associated with the phrenic motor
      pool. Although PKCzeta/iota activity is necessary for iPMF, spinal atypical PKC
      activity is not necessary for phrenic long-term facilitation (pLTF) following
      acute intermittent hypoxia, an activity-independent form of spinal respiratory
      plasticity. Thus, while iPMF and pLTF both manifest as prolonged increases in
      phrenic burst amplitude, they arise from distinct spinal cellular pathways. Our
      data are consistent with the hypotheses that (1) local mechanisms sense and
      respond to reduced respiratory-related activity in the phrenic motor pool and (2)
      inactivity-induced increases in phrenic inspiratory output require local
      PKCzeta/iota activity to stabilize into a long-lasting iPMF. Although the
      physiological role of iPMF is unknown, we suspect that iPMF represents a
      compensatory mechanism, assuring adequate motor output in a physiological system
      in which prolonged inactivity ends life.

PMID- 23152634
TI  - How glitter relates to gold: similarity-dependent reward prediction errors in the
      human striatum.
AB  - Optimal choices benefit from previous learning. However, it is not clear how
      previously learned stimuli influence behavior to novel but similar stimuli. One
      possibility is to generalize based on the similarity between learned and current
      stimuli. Here, we use neuroscientific methods and a novel computational model to
      inform the question of how stimulus generalization is implemented in the human
      brain. Behavioral responses during an intradimensional discrimination task showed
      similarity-dependent generalization. Moreover, a peak shift occurred, i.e., the
      peak of the behavioral generalization gradient was displaced from the rewarded
      conditioned stimulus in the direction away from the unrewarded conditioned
      stimulus. To account for the behavioral responses, we designed a similarity-based
      reinforcement learning model wherein prediction errors generalize across similar
      stimuli and update their value. We show that this model predicts a similarity
      dependent neural generalization gradient in the striatum as well as changes in
      responding during extinction. Moreover, across subjects, the width of
      generalization was negatively correlated with functional connectivity between the
      striatum and the hippocampus. This result suggests that hippocampus-striatal
      connections contribute to stimulus-specific value updating by controlling the
      width of generalization. In summary, our results shed light onto the neurobiology
      of a fundamental, similarity-dependent learning principle that allows learning
      the value of stimuli that have never been encountered.

PMID- 23152636
TI  - Secondary prevention in patients with vascular disease. A population based study
      on the underuse of recommended medications.
AB  - OBJECTIVES: To investigate the premorbid use of secondary prevention medications
      in patients with recurrent vascular events. DESIGN: Prospective, observational,
      population based study. SETTING: The Dijon Stroke Registry and the registry of
      myocardial infarction of Dijon and Cote d'Or, France. PATIENTS: All patients with
      cerebral ischaemia (ischaemic stroke or transient ischaemic attacks) or coronary
      artery disease (CAD) and a history of vascular disease (cerebral ischaemia, CAD
      or peripheral arterial disease (PAD)) in Dijon, France from 2006 to 2010. MAIN
      OUTCOME MEASURES: Data on medical history and prior use of treatments were
      collected. Mutivariate analyses were performed to identify predictors of the use
      of medications. RESULTS: 867 patients (614 cerebral ischaemia and 253 CAD) were
      recorded including 448 (51.7%) with a history of cerebral ischaemia only, 191
      (22.0%) with a history of CAD only, 68 (7.8%) with a history of PAD only and 160
      (18.5%) with a history of polyvascular disease. In these 867 patients, 57.3% were
      on antithrombotic therapy, 61.2% were treated with antihypertensive drugs, 32.9%
      received statins and only 23.6% were on an optimal regimen, defined as a
      combination of the three therapies. Compared with patients with previous CAD
      only, those with previous cerebral ischaemia only were less likely to be
      receiving each of these treatments or to receive an optimal regimen (OR=0.17, 95%
      CI 0.14 to 0.26, p<0.001). CONCLUSIONS: Our findings underline the fact that the
      underuse of secondary preventive therapies is common in patients with recurrent
      vascular events, especially those with previous cerebral ischaemia. This underuse
      could be targeted to reduce recurrent vascular events.

PMID- 23152635
TI  - Serotonin activates catecholamine neurons in the solitary tract nucleus by
      increasing spontaneous glutamate inputs.
AB  - Serotonin (5-HT) is a critical neurotransmitter in the control of autonomic
      functions. 5-HT(3) receptors participate in vagal afferent feedback to decrease
      food intake and regulate cardiovascular reflexes; however, the phenotype of the
      solitary tract nucleus (NTS) neurons involved is not known. A(2)/C(2)
      catecholamine (CA) neurons in the NTS are directly activated by visceral
      afferents and are important for the control of food intake and cardiovascular
      function, making them good candidates to respond to and mediate the effects of
      serotonin at the level of the NTS. This study examines serotonin's effects on NTS
      CA neurons using patch-clamp techniques and transgenic mice expressing an
      enhanced green fluorescent protein driven by the tyrosine hydroxylase (TH)
      promoter (TH-EGFP) to identify catecholamine neurons. Serotonin increased the
      frequency of spontaneous glutamate excitatory postsynaptic currents (sEPSCs) in
      >90% of NTS-TH-EGFP neurons, an effect blocked by the 5-HT(3) receptor antagonist
      ondansetron and mimicked by the 5-HT(3) receptor agonists SR5227 and mCPBG. In
      contrast, 5-HT(3) receptor agonists increased sEPSCs on a minority (<30%) of non
      TH neurons. 5-HT(3) receptor agonists increased the frequency, but not the
      amplitude, of mini-EPSCs, suggesting that their actions are presynaptic. 5-HT(3)
      receptor agonists increased the firing rate of TH-EGFP neurons, an effect
      dependent on the increased spontaneous glutamate inputs as it was blocked by the
      ionotropic glutamate antagonist NBQX, but independent of visceral afferent
      activation. These results demonstrate a cellular mechanism by which serotonin
      activates NTS-TH neurons and suggest a pathway by which it can increase
      catecholamine release in target regions to modulate food intake, motivation,
      stress, and cardiovascular function.

PMID- 23152637
TI  - The month of birth effect in multiple sclerosis: systematic review, meta-analysis
      and effect of latitude.
AB  - BACKGROUND: Month of birth has previously been described as a risk factor for
      multiple sclerosis (MS). This has been hypothesised to be related to maternal
      vitamin D levels during pregnancy, although conclusive evidence to support this
      is lacking. To date, no large studies of latitudinal variation in the month of
      birth effect have been performed to advance this hypothesis. METHODS: Previously
      published data on month of birth from 151 978 MS patients were compared to
      expected birth rates. A linear regression model was used to assess the
      relationship between latitude and observed:expected birth ratio of MS patients
      for each month. RESULTS: Analysis of all reported data demonstrated a significant
      excess of MS risk in those born in April (observed:expected 1.05, p=0.05) and
      reduction in risk in those born in October (0.95, p=0.04) and November (0.92
      p=0.01). A conservative analysis of 78 488 patients revealed an excess MS risk in
      those born in April (1.07, p=0.002) and May (1.11, p=0.0006), and a reduced risk
      in those born in October (ratio 0.94, p=0.004) and November (0.88, p=0.0002). A
      significant relationship between latitude and observed:expected ratio was
      demonstrated in December, and borderline significant relationships in May and
      August. CONCLUSIONS: Month of birth has a significant effect on subsequent MS
      risk. This is likely to be due to ultraviolet light exposure and maternal vitamin
      D levels, as demonstrated by the relationship between risk and latitude.

PMID- 23152638
TI  - Two simple tests and one complex disease.

PMID- 23152639
TI  - Intermodal four-wave mixing in a higher-order-mode fiber.
AB  - We demonstrate a high-efficiency intermodal four-wave-mixing process in an all
      fiber system, comprising a picosecond fiber laser and a high-order-mode (HOM)
      fiber. Two pump photons in the LP(01) mode of the fiber can generate an anti
      Stokes photon in the LP(01) mode and a Stokes photon in the LP(02) mode. The
      wavelength dependent mode profiles of the HOM fiber produce significant spatial
      overlap between the modes involved. The anti-Stokes wave at 941 nm is generated
      with 20% conversion efficiency with input pulse energy of 20 nJ. The guidance of
      the anti-Stokes and Stokes waves in the HOM fiber enhances system stability.

PMID- 23152640
TI  - Ultrasound-induced release of micropallets with cells.
AB  - Separation of selected adherent live cells attached on an array of microelements,
      termed micropallets, from a mixed population is an important process in
      biomedical research. We demonstrated that adherent cells can be safely,
      selectively, and rapidly released from the glass substrate together with
      micropallets using an ultrasound wave. A 3.3-MHz ultrasound transducer was used
      to release micropallets (500 MUm * 500 MUm * 300 MUm) with attached HeLa cells,
      and a cell viability of 92% was obtained after ultrasound release. The ultrasound
      induced release process was recorded by a high-speed camera, revealing a
      proximate velocity of ~0.5 m/s.

PMID- 23152641
TI  - Characteristic microvessel relaxation timescales associated with ultrasound
      activated microbubbles.
AB  - Ultrasound-activated microbubbles were used as actuators to deform microvessels
      for quantifying microvessel relaxation timescales at megahertz frequencies.
      Venules containing ultrasound contrast microbubbles were insonified by short 1
      MHz ultrasound pulses. Vessel wall forced-deformations were on the same
      microsecond timescale as microbubble oscillations. The subsequent relaxation of
      the vessel was recorded by high-speed photomicrography. The tissue was modeled as
      a simple Voigt solid. Relaxation time constants were measured to be on the order
      of ~10 MUs. The correlation coefficients between the model and 38 data sets were
      never lower than 0.85, suggesting this model is sufficient for modeling tissue
      relaxation at these frequencies. The results place a bound on potential numerical
      values for viscosity and elasticity of venules.

PMID- 23152642
TI  - Single molecule labeling of an atomic force microscope cantilever tip.
AB  - In this paper, we present a method to functionalize the very apex of an atomic
      force microscope cantilever with a single or a few molecules. In force
      spectroscopy or interaction mapping, the cantilever must be functionalized with
      only a few molecules to avoid noise or spurious measurements. Here, we covalently
      attached single molecules to the cantilever by touching it to a paper wetted with
      a solution of quantum dots. The paper competes with wicking up the hydrophilic
      surface of the tip. This method has broad applications in scanning probe
      microscopy where small numbers of molecules are needed on the tip.

PMID- 23152643
TI  - Temperature dependence of electron magnetic resonance spectra of iron oxide
      nanoparticles mineralized in Listeria innocua protein cages.
AB  - Electron magnetic resonance (EMR) spectroscopy was used to determine the magnetic
      properties of maghemite (gamma-Fe(2)O(3)) nanoparticles formed within size
      constraining Listeria innocua (LDps)-(DNA-binding protein from starved cells)
      protein cages that have an inner diameter of 5 nm. Variable-temperature X-band
      EMR spectra exhibited broad asymmetric resonances with a superimposed narrow peak
      at a gyromagnetic factor of g ~ 2. The resonance structure, which depends on both
      superparamagnetic fluctuations and inhomogeneous broadening, changes dramatically
      as a function of temperature, and the overall linewidth becomes narrower with
      increasing temperature. Here, we compare two different models to simulate
      temperature-dependent lineshape trends. The temperature dependence for both
      models is derived from a Langevin behavior of the linewidth resulting from
      "anisotropy melting." The first uses either a truncated log-normal distribution
      of particle sizes or a bi-modal distribution and then a Landau-Liftshitz
      lineshape to describe the nanoparticle resonances. The essential feature of this
      model is that small particles have narrow linewidths and account for the g ~ 2
      feature with a constant resonance field, whereas larger particles have broad
      linewidths and undergo a shift in resonance field. The second model assumes
      uniform particles with a diameter around 4 nm and a random distribution of
      uniaxial anisotropy axes. This model uses a more precise calculation of the
      linewidth due to superparamagnetic fluctuations and a random distribution of
      anisotropies. Sharp features in the spectrum near g ~ 2 are qualitatively
      predicted at high temperatures. Both models can account for many features of the
      observed spectra, although each has deficiencies. The first model leads to a
      nonphysical increase in magnetic moment as the temperature is increased if a log
      normal distribution of particles sizes is used. Introducing a bi-modal
      distribution of particle sizes resolves the unphysical increase in moment with
      temperature. The second model predicts low-temperature spectra that differ
      significantly from the observed spectra. The anisotropy energy density K(1),
      determined by fitting the temperature-dependent linewidths, was ~50 kJ/m(3),
      which is considerably larger than that of bulk maghemite. The work presented here
      indicates that the magnetic properties of these size-constrained nanoparticles
      and more generally metal oxide nanoparticles with diameters d < 5 nm are complex
      and that currently existing models are not sufficient for determining their
      magnetic resonance signatures.

PMID- 23152644
TI  - Paternal Work Stress and Latent Profiles of Father-Infant Parenting Quality.
AB  - The current study used latent profile analysis (LPA) to examine the implications
      of fathers' experiences of work stress for paternal behaviors with infants across
      multiple dimensions of parenting in a sample of fathers living in nonmetropolitan
      communities (N = 492). LPA revealed five classes of fathers based on levels of
      social-affective behaviors and linguistic stimulation measured during two father
      infant interactions. Multinomial logistic regression analyses suggested that a
      less-supportive work environment was associated with fathers' membership in
      multiple lower-quality parenting classes. Greater work pressure and a nonstandard
      work schedule also predicted fathers' membership in the latent parenting classes,
      although these associations differed depending on the number of hours fathers
      spent in the workplace.

PMID- 23152645
TI  - Education, Labor Markets, and the Retreat from Marriage.
AB  - Using data from the Fragile Families and Child Wellbeing study and Current
      Population Surveys, we find that labor market conditions play a large role in
      explaining the positive relationship between educational attainment and marriage.
      Our results suggest that if low-educated parents faced the same (stronger) labor
      market conditions as their more-educated counterparts, then differences in
      marriage by education would narrow considerably. Better labor markets are
      positively related to marriage for fathers at all educational levels. In
      contrast, better labor markets are positively related to marriage for less
      educated mothers but not their more-educated counterparts. We discuss the
      implications of our findings for theories about women's earning power and
      marriage, the current economic recession, and future studies of differences in
      family structure across education groups.

PMID- 23152646
TI  - PERTURBATION AND SCALED COOK'S DISTANCE.
AB  - Cook's (Cook, 1977) distance is one of the most important diagnostic tools for
      detecting influential individual or subsets of observations in linear regression
      for cross-sectional data. However, for many complex data structures (e.g.,
      longitudinal data), no rigorous approach has been developed to address a
      fundamental issue: deleting subsets with different numbers of observations
      introduces different degrees of perturbation to the current model fitted to the
      data and the magnitude of Cook's distance is associated with the degree of the
      perturbation. The aim of this paper is to address this issue in general
      parametric models with complex data structures. We propose a new quantity for
      measuring the degree of the perturbation introduced by deleting a subset. We use
      stochastic ordering to quantify the stochastic relationship between the degree of
      the perturbation and the magnitude of Cook's distance. We develop several scaled
      Cook's distances to resolve the comparison of Cook's distance for different
      subset deletions. Theoretical and numerical examples are examined to highlight
      the broad spectrum of applications of these scaled Cook's distances in a formal
      influence analysis.

PMID- 23152648
TI  - Racial Barrier Socialization and the Well-being of African American Adolescents:
      The Moderating Role of Mother-Adolescent Relationship Quality.
AB  - Racial socialization has been suggested as an important factor in helping African
      American adolescents cope effectively with racism and discrimination. Although
      multiple studies have reported a positive link between racial pride socialization
      and psychological adjustment among African American youth, assessments of the
      association between adolescent adjustment and another dimension of racial
      socialization-racial barrier socialization-have yielded inconsistent findings.
      Using a sample of 190 African American adolescents, the present study focuses
      attention on the quality of mother-adolescent relations as an indicator of
      affective context, and examines its moderating influence on the association
      between racial barrier socialization and adolescent adjustment. Regression
      analyses indicated that the link between racial barrier socialization and
      adolescent adjustment is moderated by mother-adolescent relationship quality.
      However, these associations varied by gender.

PMID- 23152647
TI  - COMPLIANCE, OPPOSITION, AND BEHAVIOR PROBLEMS IN TODDLERS BORN PRETERM OR LOW
      BIRTHWEIGHT.
AB  - Although children born preterm or low birth weight (PT LBW) are more likely to
      exhibit behavior problems compared to children born at term, developmental and
      family processes associated with these problems are unclear. We examined
      trajectories of maternal depressive symptoms in relation to toddler compliance
      and behavior problems in families with PT LBW infants. A total of 177 infants (93
      boys, 84 girls) and their mothers enrolled in the study during the infant's NICU
      stay. Data were collected at five time points across 2 years. Assessments of
      maternal depressive symptoms were conducted at all time points, and toddler
      compliance and opposition to maternal requests and behavior problems were
      assessed at 2 years. Toddlers born earlier with more health problems to mothers
      whose depressive symptoms increased over time exhibited the most opposition to
      maternal requests during a cleanup task at 24 months, consistent with multiple
      risk models. Mothers with elevated depression symptoms reported more behavior
      problems in their toddlers. The study has implications for family-based early
      intervention programs seeking to identify PT LBW infants at highest risk for
      problem behaviors.

PMID- 23152649
TI  - Efficacy of goniosynechialysis for advanced chronic angle-closure glaucoma.
AB  - PURPOSE: To evaluate the intraocular pressure (IOP)-lowering efficacy of
      goniosynechialysis (GSL) for advanced chronic angle-closure glaucoma (CACG) using
      a simplified slit-lamp technique. PATIENTS AND METHODS: Patients with CACG with
      one severely affected eye with best-corrected visual acuity below 20/200 and a
      mildly or functionally unaffected fellow eye were enrolled in this study. All
      patients underwent ophthalmologic examinations including measurement of visual
      acuity, best-corrected visual acuity, and IOP; biomicroscopy; specular
      microscopy; fundus examination; and gonioscopy followed by anterior chamber
      paracentesis and GSL for nasal peripheral anterior synechiae in the eye with
      severe CACG. RESULTS: Thirty patients (18 men, 12 women) were identified as
      having CACG with an initial mean IOP of 47.1 +/- 6.7 mmHg (range 39-61 mmHg) in
      the severely affected eye. One week after GSL, the mean IOP of the treated eyes
      decreased to 19.3 +/- 2.8 mmHg (range 14-26 mmHg) without antiglaucoma medication
      (average decrease 27.7 +/- 6.5 mmHg; range 16-41 mmHg), which was significant (P
      < 0.00001) compared with baseline. After an average follow-up period of 36.6 +/-
      1.0 months (range 35-38 months), the mean IOP stabilized at 17.4 +/- 2.2 mmHg
      (range 12-21 mmHg). The nasal angle recess did not close again in any one of the
      patients during the follow-up period. The average significant (P < 0.00001)
      decrease in corneal endothelial cell density in the treated eyes was 260 +/- 183
      cells/mm(2) (range 191-328 cells/mm(2)). CONCLUSIONS: Anterior chamber
      paracentesis and GSL lowers IOP in advanced CACG, though it may lead to mild
      corneal endothelial cell loss.

PMID- 23152650
TI  - Comparative efficacy of bepotastine besilate 1.5% ophthalmic solution versus
      olopatadine hydrochloride 0.2% ophthalmic solution evaluated by patient
      preference.
AB  - BACKGROUND: The aim of this study was to compare patient-perceived relief of
      ocular itch, nasal symptoms, and eye drop comfort when allergic conjunctivitis
      was treated with bepotastine besilate 1.5% versus olopatadine hydrochloride 0.2%.
      METHODS: This randomized, observer-masked, single-center, crossover study
      included 30 patients with ocular itching associated with allergic conjunctivitis
      accompanied by nasal symptoms. Patients were treated with bepotastine besilate
      1.5% twice daily (7 am and 4 pm) or olopatadine hydrochloride 0.2% once daily (7
      am) for 14 days. Following a 7-day washout period during which only preservative
      free artificial tears were used twice daily, patients were crossed over to the
      alternative treatment for 14 days. Parameters evaluated by twice-daily patient
      diaries included each treatment's ability to relieve ocular itch, ability to
      relieve itchy/runny nose, ability to relieve ocular allergy symptoms, and eye
      drop comfort. At the conclusion of the study, patients were also asked to
      identify which agent provided better all-day relief of ocular itching, better all
      day relief of itchy/runny nose, superior comfort, and for which treatment they
      would prefer a prescription. RESULTS: According to the mean daily diary
      responses, bepotastine besilate 1.5% provided significantly better relief of
      evening ocular itch, relief of morning and evening itchy/runny nose, and relief
      of morning and evening ocular allergy symptoms. At study end, 63.3% and 66.7% of
      patients preferred bepotastine besilate 1.5% for all-day relief of ocular itching
      and all-day relief of itchy/runny nose, respectively. At study end, there was no
      significant difference in the number of patients preferring one treatment over
      the other for comfort. Overall, 66.7% of patients stated that they would prefer
      to treat their allergic conjunctivitis with bepotastine besilate 1.5% over
      olopatadine hydrochloride 0.2%. CONCLUSION: Based on their evaluation of
      therapeutic performance, patients preferred bepotastine besilate 1.5% over
      olopatadine hydrochloride 0.2% by two-to-one for the treatment of allergic
      conjunctivitis.

PMID- 23152651
TI  - Early SD-OCT diagnosis followed by prompt treatment of radiation maculopathy
      using intravitreal bevacizumab maintains functional visual acuity.
AB  - PURPOSE: To evaluate the benefits of intravitreal bevacizumab in patients with
      visually compromising radiation maculopathy following iodine-125 plaque
      brachytherapy for uveal melanoma. METHODS: In this Institutional Review Board
      approved, consecutive, retrospective study from 2006-2009 of patients maintaining
      20/50 or better vision following treatment for visually compromising radiation
      maculopathy, patients were evaluated with spectral domain optical coherence
      tomography at 2-4 month intervals following plaque removal. Treatment with intra
      vitreal bevacizumab commenced at the first signs of radiation vasculopathy on
      spectral domain optical coherence tomography with associated decreased best
      corrected visual acuity, followed by repeat injections for recurrent or
      persistent vasculopathic changes. RESULTS: At 3 years following plaque
      brachytherapy, 81 of 159 (50.9%) patients treated for radiation maculopathy
      demonstrated 20/50 or better vision at median follow up of 36 months, which
      demonstrates significant improvement in vision as compared to the Collaborative
      Ocular Melanoma Study (P < 0.0001). These 81 patients were given a mean of five
      injections (range 1-17) over a mean of 17.6 months (range 1-54 months), starting
      at 15.8 months (range 3-50 months) after plaque brachytherapy. For those eyes
      that maintained 20/50 or better vision at the final follow-up, pretreatment mean
      best corrected visual acuity of 20/43 improved to 20/31. CONCLUSION: This study
      demonstrates that spectral domain optical coherence tomography can detect early
      vasculopathic changes secondary to radiation maculopathy and that prompt
      treatment with intravitreal bevacizumab may delay vision loss and maintain or
      possibly improve visual acuity in half of eyes diagnosed with radiation
      maculopathy. Radiation maculopathy remains a therapeutically manageable morbidity
      associated with radiation therapy for posterior uveal melanoma.

PMID- 23152652
TI  - Quality of life of glaucoma patients under medical therapy with different
      prostaglandins.
AB  - PURPOSE: To assess the quality of life of glaucoma patients under medical therapy
      with different prostaglandin analogs. METHODS: A cross-sectional study of
      consecutive glaucoma patients was designed. We assessed the patients' quality of
      life through the Brazilian 25-question version of the National Eye Institute
      Visual Functioning Questionnaire, comprising 12 subscales (general health,
      general vision, ocular pain, near vision, distance vision, social function,
      mental health, role limitations, dependency, driving, color vision, and
      peripheral vision) and a total composite score. Clinical features, including
      current medical treatment, were obtained from each patient's medical record.
      Three groups of patients were identified according to the prostaglandin in use:
      bimatoprost, latanoprost, or travoprost. The main outcome measures were: mean
      score in each subscale and mean total composite score. RESULTS: The mean total
      composite score for the whole group was 70.60. The bimatoprost, latanoprost, and
      travoprost groups had the following mean composite scores, respectively: 56.56,
      77.36, and 71.08 (P = 0.001, analysis of variance [ANOVA]). Latanoprost and
      travoprost results were similar, and both were superior to bimatoprost. Most
      subscales had similar results. The subscale with the lowest score for all groups
      was general health. Groups were homogenous and comparable. CONCLUSION: There is a
      difference in the quality of life between glaucoma patients using prostaglandin
      analogs. It seems that bimatoprost users have lower QoL when compared to
      latanoprost and travoprost users.

PMID- 23152653
TI  - Deposit buildup on prosthetic eyes and implications for conjunctival inflammation
      and mucoid discharge.
AB  - BACKGROUND: The aim of this study was to investigate deposit buildup on
      prosthetic eyes and the implications for conjunctival inflammation and discharge.
      METHODS: Forty-three prosthetic eye wearers participated in the study. Twenty
      three had their prostheses polished normally before being worn continuously for 2
      weeks. After this time, surface deposits were stained, photographed, and graded.
      The prostheses were then repolished to optical quality contact lens standard and
      worn for a further 2 weeks, when the deposits were again stained, photographed,
      and graded. Two participants had deposits on their prostheses stained,
      photographed, and graded on nine occasions at decreasing intervals ranging from 1
      year to 1 day. Eighteen participants had the wetting angles on their prostheses
      measured with a goniometer before and after cleaning, after polishing normally,
      after polishing to optical quality contact lens standard, and after 10 minutes of
      wearing their optical quality contact lens polished prostheses. Concordance
      correlation, multiple regression, and paired t-tests were used for the
      statistical analysis. RESULTS: More surface deposits accumulated on prostheses
      polished normally than on those polished to an optical quality contact lens
      standard after 2 weeks of wear. The interpalpebral zone of most prostheses
      (observed without magnification) appeared to be clear of deposits. Removal of
      deposits significantly decreased surface wettability, but wettability returned
      after 10 minutes of wear. Optical quality contact lens polishing produced more
      wettable surfaces and a slower rate of deposit accumulation than normal
      polishing. CONCLUSION: We recommend that an optical quality contact lens standard
      be the minimum standard of finish for prosthetic eyes. This standard may assist
      the smooth action of the lids over the interpalpebral zone of the prosthesis and
      the cleansing action of tears. The presence of deposits in the retropalpebral
      zone may improve the lubricating properties of socket fluids which, in turn, may
      result in less frictional irritation of the conjunctiva and less mucoid
      discharge.

PMID- 23152654
TI  - Impending anterior ischemic optic neuropathy with elements of retinal vein
      occlusion in a patient on interferon for polycythemia vera.
AB  - We describe the course and likely pathophysiology of impending anterior ischemic
      optic neuropathy (AION) and retinal vein occlusion in a 56-year-old man with
      polycythemia vera managed with interferon alpha for 2 years. Our patient
      presented with decreased vision, scintillating scotomata, and floaters. Fundus
      examination findings and results of a fluorescein angiogram led to the diagnosis
      of impending AION and retinal vein occlusion. Considering that both polycythemia
      vera and interferon have possible influences on vascular occlusion and optic disc
      edema, we stopped interferon treatment and immediately attempted to treat the
      polycythemia vera empirically with pentoxifylline and any interferon-associated
      inflammation with prednisone. Our patient experienced complete resolution of
      fundus abnormalities and return of normal vision within 3 weeks, which may be
      attributed to our successful treatment of both etiologies. Thus, further study is
      warranted to elucidate the treatment of both polycythemia vera and interferon
      induced impending AION.

PMID- 23152655
TI  - Two-step surgery for retinal detachment caused by myopic macular hole.
AB  - PURPOSE: To report the results of a two-step operation for treating retinal
      detachments caused by macular holes in high-myopic patients. METHODS: In the
      first part of the operation, pars plana vitrectomy, air-fluid exchange, and
      silicone oil injection were performed. At 4-6 months after the first operation,
      the second part of the operation was performed. This involved silicone oil
      removal and internal limiting membrane peeling under the aid of triamcinolone
      acetonide with or without gas tamponade. RESULTS: Four eyes (four patients)
      underwent surgery with this technique. All retinas were attached at the time of
      the second operation, when internal limiting membrane peeling could be performed
      easily and safely. The retina remained attached in all four eyes (100%) during 24
      32 months of follow-up after the second operation. CONCLUSION: Favorable surgical
      results were obtained with the two-step operation in the treatment of retinal
      detachments resulting from myopic macular holes.

PMID- 23152657
TI  - Transepithelial corneal collagen cross-linking in ultrathin keratoconic corneas.
AB  - BACKGROUND: The purpose of this paper was to report the results of
      transepithelial corneal collagen cross-linking (CXL) with modified riboflavin and
      ultraviolet A irradiation in patients affected by keratoconus, each with thinnest
      pachymetry values of less than 400 MUm (with epithelium) and not treatable using
      standard de-epithelialization techniques. METHODS: Sixteen patients affected by
      progressive keratoconus with thinnest pachymetry values ranging from 331 MUm to
      389 MUm underwent transepithelial CXL in one eye using a riboflavin 0.1% solution
      in 15% Dextran T500 containing ethylenediamine tetra-acetic acid 0.01% and
      trometamol to enhance epithelial penetration. The patients underwent complete
      ophthalmological examination, including endothelial cell density measurements and
      computerized videokeratography, before CXL and at one day, one week, and one, 6,
      and 12 months thereafter. RESULTS: Epithelial healing was complete in all
      patients after one day of use of a soft bandage contact lens. No side effects or
      damage to the limbal region was observed during the follow-up period. All
      patients showed slightly improved uncorrected and spectacle-corrected visual
      acuity; keratometric astigmatism showed reductions (up to 5.3 D) and apical
      ectasia power decreased (K(max) values reduced up to 4.3 D). Endothelial cell
      density was unchanged. CONCLUSION: Application of transepithelial CXL using
      riboflavin with substances added to enhance epithelial permeability was safe,
      seemed to be moderately effective in keratoconic eyes with ultrathin corneas, and
      applications of the procedure could be extended to patients with advanced
      keratoconus.

PMID- 23152656
TI  - Laser refractive surgery in diabetic patients: a review of the literature.
AB  - BACKGROUND: The purpose of this study was to evaluate the current recommendations
      regarding laser refractive surgery in patients with diabetes mellitus and to
      assess whether these patients make appropriate candidates for laser vision
      correction. METHODS: A literature search was conducted to identify current
      research on the ocular complications of diabetes and original publications on
      laser refractive surgery in diabetic patients. RESULTS: Diabetes was associated
      with several ocular complications. Initially the US Food and Drug Administration
      listed these complications as justification to advise against refractive surgery
      in patients with diabetes. However, recent studies on laser in situ
      keratomileusis in diabetic patients indicate that this procedure may be safe in
      diabetic patients with very well controlled systemic disease and no ocular
      manifestations. CONCLUSION: Laser refractive surgery may be performed safely in a
      very selected group of patients with diabetes.

PMID- 23152658
TI  - Simultaneous topography-guided PRK followed by corneal collagen cross-linking
      after lamellar keratoplasty for keratoconus.
AB  - BACKGROUND: The purpose of this paper is to report the results of using combined
      treatment of customized excimer laser-assisted photorefractive keratectomy (PRK)
      and prophylactic corneal collagen crosslinking (CXL) for residual refractive
      error in a group of patients who had previously undergone lamellar keratoplasty
      for keratoconus. METHODS: The study included 14 eyes from 14 patients who had
      originally been treated for keratoconus in one eye by excimer laser-assisted
      lamellar keratoplasty (ELLK), and subsequently presented with residual ametropia
      (-6.11 D +/- 2.48, range -2.50 to -9.50). After a mean 40.1 +/- 12.4 months since
      ELLK they underwent combined simultaneous corneal regularization treatment with
      topographically guided transepithelial excimer laser PRK (central corneal
      regularization) and corneal CXL induced by riboflavin-ultraviolet A. RESULTS:
      After a mean 15 +/- 6.5 (range 6-24) months, all eyes gained at least one Snellen
      line of uncorrected distance visual acuity (range 1-10). No patient lost lines of
      corrected distance visual acuity, and four patients gained three lines of
      corrected distance visual acuity. Mean manifest refractive spherical equivalent
      was -0.79 +/- 2.09 (range +1 to -3.0) D, and topographic keratometric astigmatism
      was 5.02 +/- 2.93 (range 0.8-8.9) D. All the corneas remained clear (haze < 1).
      CONCLUSION: The combination of customized PRK and corneal CXL provided safe and
      effective results in the management of corneal regularization for refractive
      purposes after ELLK for keratoconus.

PMID- 23152659
TI  - Corneal ectasia after myopic laser in situ keratomileusis: a long-term study.
AB  - BACKGROUND: The purpose of this study was to evaluate the long-term postoperative
      incidence of and key factors in the genesis of corneal ectasia after myopic laser
      assisted in situ keratomileusis (LASIK) in a large number of cases. METHODS: A
      retrospective review of one surgeon's myopic LASIK database was performed.
      Patients were stratified into two groups based on date of surgery, ie, group 1
      (1313 eyes) from 1999 to 2001 and group 2 (2714 eyes) from 2001 to 2003. Visual
      acuity, refraction, pachymetry, and corneal topography data were available for
      each patient from examinations performed both before and after the refractive
      procedures. RESULTS: Of the 4027 surgically treated eyes, 23 (0.57%) developed
      keratectasia during the follow-up period, which was a minimum seven years; nine
      eyes (0.69%) were from group 1 and 14 eyes (0.51%) were from group 2. The onset
      of corneal ectasia was at 2.57 +/- 1.04 (range 1-4) years and 2.64 +/- 1.29
      (range 0.5-5) years, respectively, for groups 1 and 2. The most important
      preoperative risk factors using the Randleman Ectasia Risk Score System were
      manifest refractive spherical error in group 1 and a thin residual stromal bed in
      group 2. Each of the cases that developed corneal ectasia had risk factors that
      were identified. CONCLUSION: Ectasia was an uncommon outcome after an otherwise
      uncomplicated laser in situ keratomileusis procedure. The variables present in
      eyes developing postoperative LASIK ectasia can be better understood using the
      Randleman Ectasia Risk Score System.

PMID- 23152660
TI  - Combination of a modified Hotz procedure with the Jones procedure decreases the
      recurrence of involutional entropion.
AB  - PURPOSE: Involutional entropion is a common condition in Asian countries,
      including Japan. One cause of involutional entropion is weakening of the
      capsulopalpebral fascia (CPF). The aged, thin, membranous nature of the CPF
      limits the results of correction by the original Jones procedure (CPF tightening)
      alone, so we added the modified Hotz procedure to the entropion repair. We then
      compared the recurrence rates and operation times in corrections performed with
      and without this additional procedure. CASES: From April 2010 to December 2011,
      one surgeon performed lower-lid surgery using the Jones procedure with the
      addition of the modified Hotz procedure. Fifteen patients (a total of 21 eyes)
      underwent this combined procedure. Previously, the same surgeon performed the
      Jones procedure alone for eight patients (a total of nine eyes). RESULTS: The
      average age of the two groups was 76.4 years, with an age range of 66-85 years.
      All cases reported acceptable ciliary orientation at the end of the surgery.
      However, patients who underwent the Jones procedure alone (nine eyes total)
      reported three cases of recurrence after at least 6 months of follow-up. Patients
      who underwent the combined procedure reported two complications: one recurrence
      and one ectropion. The recurrence rate was 5%. The Jones procedure using eyelid
      pinch required an average of 22.6 minutes to complete; the combined method
      required 33.4 minutes to complete. CONCLUSION: The combined method resulted in a
      significantly higher success rate than the Jones procedure alone (P < 0.05). The
      5% failure rate of the combined method was found to be superior to the 30%
      recurrence rate of the Jones procedure. As a result, the Hotz procedure enhanced
      the results of the entropion correction and required only 10 additional minutes
      of surgery. We now perform this combined procedure for all cases.

PMID- 23152661
TI  - Decalcified choroidal osteoma found in the retina.
AB  - Choroidal osteoma is a benign tumor of the choroid. Herein, we report a rare case
      of decalcified choroidal osteoma found in the retina. A 27-year-old woman
      presented with visual loss. Her best-corrected visual acuity was 20/50 OS.
      Ophthalmoscopy of the left eye revealed a yellow-white calcified region
      accompanied by a decalcified region of four disc diameters in size. After 6
      years, spectral-domain optical coherence tomography showed a tumor projected
      strongly upwards from the choroid and partially through the retina with serous
      retinal detachment, with both a lamellar appearance and mound-like area. The
      calcified region became more contractive than was observed on the first visit.
      Conversely, the decalcified region was wider than was observed on the first
      visit. Her best-corrected visual acuity was 20/400 OS. Choroidal osteoma was
      worsened by progression of decalcification. The decalcified choroidal osteoma
      resulted in poor visual acuity, and projected strongly upward from the choroid
      and into the retina.

PMID- 23152663
TI  - Meridional lenticular astigmatism associated with bilateral concurrent uveal
      metastases in renal cell carcinoma.
AB  - PURPOSE: To demonstrate a case illustrating meridional lenticular astigmatism as
      a result of renal cell carcinoma uveal metastases. METHODS: Case report with
      images. RESULTS: Clinical findings and diagnostic testing of a patient with
      acquired meridional lenticular astigmatism are described. The refraction revealed
      best-corrected visual acuity of 20/20-1 OD (-2.50 + 0.25 * 090) and 20/50 OS (
      8.25 + 3.25 * 075). Bilateral concurrent renal cell carcinoma metastases to the
      choroid and ciliary body are demonstrated by utilizing ultrasonography,
      ultrawidefield fluorescein angiography, and unique spectral-domain optical
      coherence tomography. CONCLUSIONS: Metastatic disease should be included in the
      differential of acquired astigmatism. Spectral-domain optical coherence
      tomography, ultrawidefield fluorescein angiography, and ultrasonography have
      roles in delineating choroidal metastases.

PMID- 23152662
TI  - Laser in situ keratomileusis in patients with collagen vascular disease: a review
      of the literature.
AB  - PURPOSE: To evaluate the current United States Food and Drug Administration (FDA)
      recommendations regarding laser in situ keratomileusis (LASIK) surgery in
      patients with collagen vascular diseases (CVD) and assess whether these patients
      make appropriate candidates for laser vision correction, and offer treatment
      recommendations based on identified clinical data. METHODS: A literature search
      was conducted using PubMed, Medline, and Ovid to identify all existing studies of
      LASIK in patients with collagen vascular diseases. The search was conducted
      without date limitations. Keywords used for the search included MeSH terms: laser
      in situ keratomileusis, LASIK, refractive surgery, ocular surgery, and cataract
      surgery connected by "and" with the following MeSH and natural-language terms:
      collagen vascular disease, rheumatic disease, systemic disease, rheumatoid
      arthritis, systemic lupus erythematosus, Sjogren's syndrome, seronegative
      spondyloarthropathy, HLA B27, ankylosing spondylitis, reactive arthritis,
      psoriatic arthritis. The abstracts for all studies meeting initial search
      criteria were reviewed; relevant studies were included. No prospective studies
      were found; however, four retrospective case studies were identified that
      examined LASIK surgery in patients with CVD. Several case reports were also
      identified in similar fashion. RESULTS: The FDA considers CVD a relative
      contraindication to LASIK surgery, due largely to the ocular complications
      associated with disease in the CVD spectrum. However, recent studies of LASIK in
      patients with CVD indicate LASIK may be safe for patients with very well
      controlled systemic disease, minimal ocular manifestations, and no clinical signs
      or history of dry-eye symptoms. CONCLUSION: LASIK surgery may be safe in patients
      with rheumatoid arthritis or systemic lupus erythematosus and the seronegative
      spondyloarthropathies if stringent preoperative criteria are met. Evidence
      suggests patients with Sjogren's syndrome are not suitable candidates for LASIK.

PMID- 23152664
TI  - Posterior segment causes of reduced visual acuity after phacoemulsification in
      eyes with cataract and obscured fundus view.
AB  - PURPOSE: To determine posterior segment causes of reduced visual acuity after
      phacoemulsification in eyes with cataract and obscured fundus view. PATIENTS AND
      METHODS: Retrospective review of medical records of patients with cataract,
      obscured fundus view, and normal B-scan ultrasonography, undergoing
      phacoemulsification from May 2005 to March 2012 was conducted. Eyes with fundus
      pathology, previous trauma, surgery, glaucoma, amblyopia, or uveitic cataract
      were excluded. Ocular comorbid conditions, preoperative visual acuity (VA),
      intraoperative and early postoperative complications, and final best corrected
      visual acuity (BCVA) at 1 month were abstracted from the records. RESULTS: All
      201 eyes of 179 patients studied had a preoperative VA of <=6/60. Preoperative
      ocular comorbidity was present in 31 eyes (15.5%). Intraoperative complications
      occurred in 20 eyes (10%). Postoperative complications developed in 34 eyes
      (17.0%). One month postoperatively, 175 eyes (87.1%) achieved a BCVA of >=6/12;
      whereas 26 eyes (12.9%) achieved a BCVA of <=6/18. The most common posterior
      segment causes of reduced VA in the 26 eyes were age-related macular disease in
      ten eyes (38.5%) and diabetic maculopathy in six eyes (23.1%). Similar fundus
      pathology was seen preoperatively in the fellow fundus in 10 of the 26 eyes
      (38.5%). CONCLUSION: One month after phacoemulsification in eyes with cataract
      and obscured fundus view, age-related macular disease and diabetic maculopathy
      were the most common posterior segment causes of reduced final BCVA. To avoid
      postsurgical dissatisfaction, patients with obscured fundus view in their
      preoperative eye should be counseled, especially if posterior segment pathology
      exists in their fellow eye.

PMID- 23152665
TI  - The use of antimetabolites as adjunctive therapy in the surgical treatment of
      pterygium.
AB  - BACKGROUND: Pterygium is a proliferative disease with hyperplastic growth of
      corneoconjunctival fibro vascular tissue onto the cornea. Surgical therapy can be
      used to successfully manage pterygia; however, recurrence remains a problem. To
      reduce recurrence, surgical management may include autoconjunctival grafting,
      lamellar keratoplasty, amniotic membrane transplantation, and intraoperative
      antimetabolites application. PURPOSE: To assess the safety and the efficacy of
      intraoperative mitomycin C (MMC) and 5-fluorouracil (5-FU) application in
      preventing recurrence of pterygium after excision. PATIENTS AND METHODS: The
      study design is a prospective, randomized clinical trial. A total of 50 patients
      with bilateral pterygium were recruited for the study. The first group of
      patients (25) underwent surgical excision of the pterygium with bare sclera in
      one eye and MMC was applied as adjunctive therapy for the other eye. In the
      second group 5-FU was used instead of MMC. Recurrences and postoperative
      complications were measured in the two groups. The mean follow up period of the
      patients was 18.8 months. Chi square test, odds ratio, and frequency distribution
      were used to determine significance levels; P-values <0.05 were considered
      statistically significant. RESULTS: In group 1 the recurrence rate was 8% for the
      MMC treated eyes and 32% for their fellow eyes (P = 0.03). In group 2 the rate
      was 18% for the 5-FU treated eyes and 34% for their fellow eyes (P = 0.07). No
      serious complications were recorded in either group. CONCLUSION: Both MMC and 5
      FU reduce the recurrence rate of pterygium after simple surgical excision;
      statistically, the effect of the former was significant, but insignificant for
      the latter. Both antimetabolites were safe during the whole study period, but 5
      FU recurrent cases showed cosmetically unacceptable appearances with excessive
      vascularization. MMC, but not 5-FU, is recommended as an adjunctive therapy to
      prevent recurrence of pterygium after surgical excision.

PMID- 23152666
TI  - Efficacy of pneumatic displacement with 40-degree downward gaze positioning for
      treatment of submacular hemorrhage: report of two cases.
AB  - BACKGROUND: Two retrospective case reports are described showing the efficacy of
      pneumatic displacement with 40-degree downward gaze positioning for treatment of
      submacular hemorrhage. Case 1 involved an 85-year-old woman who visited our
      clinic with a complaint of blurred vision in her right eye. Best corrected visual
      acuity (BCVA) of the right eye was hand motion. Her right eye showed a submacular
      hemorrhage with retinal macroaneurysm. Prone positioning was difficult because of
      the patient's age and obesity. The treatment method was pneumatic displacement
      with 40-degree downward gaze positioning after intravitreal injection of 100%
      sulfur hexafluoride gas. After the treatment, the hemorrhage moved downward and
      BCVA of her right eye was 0.1. Case 2 involved a 58-year-old man with a complaint
      of blurred vision in his left eye. BCVA of his left eye was 0.3 and submacular
      hemorrhage was observed. He underwent displacement of the hemorrhage as
      previously described. After treatment, the submacular hemorrhage moved downward.
      Angiography detected a polypoidal lesion with a vascular network. upon diagnosis
      of polypoidal choroidal vasculopathy, bevacizumab was injected intravitreally.
      Two months after gas injection, the submacular hemorrhage disappeared. Optical
      coherence tomography showed flattening of the submacular retinal pigment
      epithelium, which was not observed prior to bevacizumab therapy. BCVA of the
      patient's left eye was 0.9. Pneumatic displacement with 40-degree downward gaze
      positioning after intravitreal sulfur hexafluoride injection is useful to
      displace a submacular hemorrhage. Early application of this treatment provides
      improvement of vision and facilitates fundus examination, which could reveal the
      cause of the submacular hemorrhage.

PMID- 23152667
TI  - Role of CD44 as a marker of cancer stem cells in head and neck cancer.
AB  - In recent years, many studies have shown that some types of tumors are
      characterized by the presence of cells with stem-like characteristics, called
      cancer stem cells (CSCs). These are considered cells that initiate the tumor and
      are probably responsible for tumor recurrence. CSCs have the capacity for self
      renewal, the potential to give rise to one or more cell types within the tumor,
      and the ability to drive, in a continuous manner, the proliferation of malignant
      cells. The failure of current cancer therapies can be attributed to the relative
      ineffectiveness of drugs against CSCs, which remain viable while retaining their
      full ability to reproduce the tumor. The development of new strategies is
      currently hampered by the lack of reliable markers to identify CSCs. One
      promising surface marker of CSCs in head and neck cancer is the CD44 molecule,
      which has been shown in preliminary studies to have high specificity, although
      there are discrepant data because its prognostic value may depend on the specific
      tumor location. More rigorous studies are needed to investigate the usefulness of
      CD44 expression in head and neck tumors for possible clinical applicability.

PMID- 23152668
TI  - Belatacept for prevention of acute rejection in adult patients who have had a
      kidney transplant: an update.
AB  - In June 2011, the US Food and Drug Administration approved belatacept for the
      prophylaxis of organ rejection in adult kidney transplant recipients. This review
      discusses the use of belatacept for the prevention of acute rejection as part of
      a maintenance immunosuppression regimen. Belatacept is a selective costimulation
      blocker designed to provide effective immunosuppression while avoiding the
      toxicities associated with calcineurin inhibitors. Phase III trial data have
      demonstrated that belatacept is noninferior to cyclosporine in 1-year patient and
      allograft survival. Three-year data demonstrate an ongoing improvement in mean
      measured glomerular filtration rate in belatacept-treated versus cyclosporine
      treated patients. However, the rate of acute rejection was higher in belatacept
      treated patients compared with cyclosporine. Specifically, there was a higher
      incidence of Banff type II rejections in patients treated with belatacept.
      Despite the higher Banff grade, rejections on belatacept were not associated with
      other factors associated with poor outcomes, such as the development of donor
      specific antibodies or reduced estimated glomerular filtration rate. One safety
      issue that must be considered when using belatacept is the potential for
      increased risk of post-transplant lymphoproliferative disease. There were more
      cases of post-transplant lymphoproliferative disease in belatacept-treated
      patients, especially in recipients seronegative for Epstein-Barr virus or
      patients treated with lymphocyte-depleting agents. Therefore, belatacept can be
      recommended for use in Epstein-Barr virus antibody-positive recipients.

PMID- 23152669
TI  - Potent human uric acid transporter 1 inhibitors: in vitro and in vivo metabolism
      and pharmacokinetic studies.
AB  - Human uric acid transporter 1 (hURAT1; SLC22A12) is a very important urate anion
      exchanger. Elevated urate levels are known to play a pivotal role in
      cardiovascular diseases, chronic renal disease, diabetes, and hypertension.
      Therefore, the development of potent uric acid transport inhibitors may lead to
      novel therapeutic agents to combat these human diseases. The current study
      investigates small molecular weight compounds and their ability to inhibit 14C
      urate uptake in oocytes expressing hURAT1. Using the most promising drug
      candidates generated from our structure-activity relationship findings, we
      subsequently conducted in vitro hepatic metabolism and pharmacokinetic (PK)
      studies in male Sprague-Dawley rats. Compounds were incubated with rat liver
      microsomes containing cofactors nicotinamide adenine dinucleotide phosphate and
      uridine 5'-diphosphoglucuronic acid. In vitro metabolism and PK samples were
      analyzed using liquid chromatography/mass spectrometry-mass spectrometry methods.
      Independently, six different inhibitors were orally (capsule dosing) or
      intravenously (orbital sinus) administered to fasting male Sprague-Dawley rats.
      Blood samples were collected and analyzed; these data were used to compare in
      vitro and in vivo metabolism and to compute noncompartmental model PK values.
      Mono-oxidation (Phase I) and glucuronidation (Phase II) pathways were observed in
      vitro and in vivo. The in vitro data were used to compute hepatic intrinsic
      clearance, and the in vivo data were used to compute peak blood concentration,
      time after administration to achieve peak blood concentration, area under the
      curve, and orally absorbed fraction. The experimental data provide additional
      insight into the hURAT1 inhibitor structure-activity relationship and in vitro-in
      vivo correlation. Furthermore, the results illustrate that one may successfully
      prepare potent inhibitors that exhibit moderate to good oral bioavailability.

PMID- 23152670
TI  - The relationship between patient satisfaction with service quality and survival
      in pancreatic cancer.
AB  - PURPOSE: Despite the recognized relevance of symptom burden in pancreatic cancer,
      there has been limited exploration of whether an individual patient's
      satisfaction with the overall quality of care received might influence outcome.
      We evaluated the relationship between patient satisfaction with health service
      quality and survival in patients with pancreatic cancer. PATIENTS AND METHODS: A
      random sample of 496 pancreatic cancer patients treated at Cancer Treatment
      Centers of America((r)) (CTCA) between July 2007 and December 2010. A
      questionnaire that covered several dimensions of patient satisfaction was
      administered. Items were measured on a seven-point Likert scale ranging from
      "completely dissatisfied" to "completely satisfied." Patient survival was the
      primary end point. Cox regression was used to evaluate the association between
      patient satisfaction and survival. RESULTS: The response rate for this study was
      72%. Of the 496 patients, 345 (69.6%) reported being "completely satisfied" with
      the care provided. Median overall survival was 7.9 months. On univariate
      analysis, patients reporting they were "completely satisfied" experienced
      superior survival compared with patients stating they were "not completely
      satisfied" (hazard ratio = 0.62; 95% confidence interval: 0.50-0.77; P < 0.001).
      On multivariate analysis controlling for stage at diagnosis, treatment history,
      and specific CTCA treatment center, "completely satisfied" patients demonstrated
      significantly lower mortality (hazard ratio = 0.63; 95% confidence interval: 0.51
      0.79; P < 0.001). CONCLUSION: In this exploratory analysis, patient satisfaction
      with health service quality was an independent predictor of survival in
      pancreatic cancer. Further exploration of a possible meaningful relationship
      between patient satisfaction with the care they have received and outcome in this
      difficult malignancy is indicated.

PMID- 23152671
TI  - Gender-specific external barriers to seeking care for urinary incontinence.
AB  - BACKGROUND: Barriers to seeking care for urinary incontinence are specific,
      objective, external conditions that prevent incontinence sufferers from seeking
      treatment. The aim of this study was to compare barriers, gender, and health care
      disparities in incontinence sufferers. METHODS: Incontinent patients were
      recruited into a questionnaire-based cross-sectional study. The 14-item Barriers
      to Incontinence Care Seeking Questionnaire (BICS-Q) and the three-item
      International Consultation on Incontinence Questionnaire-Urinary Incontinence
      Short Form (ICIQ-UI SF) were used to evaluate barriers to seeking health care for
      urinary incontinence. RESULTS: The representative sample (n = 1014) finally
      included 567 adults eligible to participate in this study (response rate 55.9%).
      Of the 147 incontinent males, 93 (63.3%) did not seek care, and of the 420
      incontinent females, 282 (67.1%) did not seek care. Untreated males had
      significantly higher BICS-Q scores than other patients. Risk factors for barriers
      were obesity (odds ratio 2.13 for females versus 0.83 for males), stress urinary
      incontinence (1.57 versus 9.38, respectively), and urgency urinary incontinence
      (2.40 versus 1.75). CONCLUSION: The barriers to seeking care for urinary
      incontinence seem to be gender-specific. Obese females with urgency urinary
      incontinence and males with stress urinary incontinence were least likely to seek
      treatment.

PMID- 23152672
TI  - Evaluating aesthetics of the nasolabial region in children with cleft lip and
      palate: professional analysis and patient satisfaction.
AB  - Cleft lip and palate is one of the most common deformities of the craniofacial
      region, and treatment of this deformity is essential for social reintegration.
      One of the major goals of surgery and treatment of craniofacial deformities is to
      improve the aesthetic appearance of the face, and thereby improve the patient's
      social acceptability. Here, we present a critical review of the criteria for
      aesthetic evaluation of the nasolabial region in cleft patients by assessing
      publications with the highest level of evidence, including professional
      evaluation, and patient satisfaction. The findings indicate treatment of this
      condition represents a major challenge for multidisciplinary team care.

PMID- 23152673
TI  - Adherence to lipid-lowering treatment: the patient perspective.
AB  - Despite the widespread prescription of highly effective lipid-lowering
      medications, such as the HMG-CoA reductase inhibitors (statins), a large portion
      of the population has lipid levels higher than the recommended goals. Treatment
      failures have been attributed to a variety of causes but the most important is
      likely to be poor adherence to therapy in the form of irregular or interrupted
      intake and the high frequency of discontinuation or lack of persistence.
      Adherence is a multidimensional phenomenon determined by the interplay of patient
      factors, physician factors, and health care system factors. Patients' knowledge
      and beliefs about their illness, motivation to manage it, confidence in their
      ability to engage in illness-management behaviors, and expectations regarding the
      outcome of treatment and the consequences of poor adherence interact to influence
      adherence behavior. Patient-related factors account for the largest incremental
      explanatory power in predicting adherence. This article provides an overview of
      this critical issue, focusing on patient role in determining adherence level to
      lipid-lowering therapy.

PMID- 23152674
TI  - The impact of telemonitoring upon hospice referral in the community: a randomized
      controlled trial.
AB  - BACKGROUND: Using telemedicine for older adults with multiple comorbid conditions
      is a potential area for growth in health care. Given this older, ailing
      population, providers should discuss end-of-life care with patients. OBJECTIVE:
      To determine the relationship between telemonitoring and hospice enrollment
      compared to usual care among older adults with chronic health problems. METHODS:
      This was a secondary evaluation of a randomized controlled trial. The trial was
      performed at an academic medical center. Patients who were over the age of 60 and
      had a high risk of hospitalization and emergency department visits were recruited
      to the study. The primary outcome was hospice enrollment, and the secondary
      outcome was the mean number of days in hospice. The data were analyzed using Chi
      squared tests and time-to-event analysis. RESULTS: The average age of the cohort
      was 80.3 years. Nine patients (9.6%) in the telemonitoring group were enrolled in
      hospice care, whereas four patients (4.0%) in the usual care group were enrolled
      (P = 0.12). The mean number of days in hospice was 57.9 (SD +/- 99.2) for the
      telemonitoring group, and 119.3 (SD +/- 123.8) for the usual care group (P =
      0.36). There was no significant difference regarding time to hospice referral.
      CONCLUSION: In this pilot analysis, there were no differences noted between
      groups in the number of patients that entered into hospice or the amount of time
      they stayed in hospice care. This was a small trial, and the power to detect a
      difference was 36%. It was encouraging that twice the number of patients enrolled
      in hospice care in the telemonitoring group compared to usual care despite the
      insignificant finding. Further research may determine the effect of
      telemonitoring upon hospice referral.

PMID- 23152676
TI  - A prospective study of risk factors for cardiovascular events among the elderly.
AB  - OBJECTIVE: To analyze the impact of cardiovascular (CV) risk factors on the
      occurrence of fatal and non-fatal CV events in elderly individuals. METHODS: The
      present research was a prospective cohort study of 800 elderly Brazilian
      outpatients (60 to 85 years old) with a 12-year follow-up period (baseline: 1997
      1998). The outcome variable was CV mortality or non-fatal CV events (stroke,
      infarction, angina, heart failure). Hypertension, diabetes, global and abdominal
      obesity, dyslipidemias, and metabolic syndrome were analyzed as independent
      variables. The analyses were based on Cox proportional hazard models and adjusted
      for gender, age range, smoking, regular physical activity, and previous
      cardiovascular disease. RESULTS: A total of 233 fatal and non-fatal CV events
      were observed (29.1%). In the adjusted analysis, the following variables were
      associated with CV risk: hypertension hazard ratio (HR): 1.69; confidence
      interval (CI) 95%: 1.28-2.24, diabetes (HR: 2.67; CI 95%: 1.98-3.61), metabolic
      syndrome (HR: 1.61; CI 95%: 1.24-2.09), abdominal obesity (HR: 1.36; CI 95%: 1.03
      1.79), hypertriglyceridemia (HR: 1.67; CI 95%: 1.22-2.30) and high
      triglyceride/HDL-c ratio (HR: 1.73; CI 95%: 1.31-2.84). Hypertension, diabetes,
      and dyslipidemia remained associated with CV risk regardless of abdominal
      obesity. CONCLUSION: In this prospective study, hypertension, diabetes, metabolic
      syndrome, abdominal obesity, and hypertriglyceridemia were predictors of CV risk
      in elderly individuals. These results confirm the relevance of controlling these
      CV risk factors in this age group.

PMID- 23152675
TI  - Pneumonia immunization in older adults: review of vaccine effectiveness and
      strategies.
AB  - Vaccination remains the primary preventive strategy in the elderly against
      Streptococcus pneumoniae and influenza infections. The effectiveness of this
      strategy in preventing pneumonia has been in doubt despite the increase in
      vaccination coverage among older adults. Randomized controlled trials (RCTs) and
      observational studies aimed at determining clinical outcomes and immune response
      following pneumococcal vaccination have yielded conflicting results. The
      protective efficacy of pneumococcal vaccination against pneumonia in older adults
      has not been firmly established due to a lack of RCTs specifically examining
      patients >= 65 years of age. Similarly, the reported benefits of influenza
      vaccination have been derived from observational data. The assessment of clinical
      benefit from influenza vaccination in the elderly population is complicated by
      varying cohorts, virulence of the influenza strain, and matching of vaccine and
      circulating viral strains. The presence of selection bias and use of nonspecific
      end points in these studies make the current evidence inconclusive in terms of
      overall benefit. The development of more immunogenic vaccines through new
      formulations or addition of adjuvants holds the promise of revolutionizing
      delivery and improving efficacy. Dismantling existing barriers through education,
      providing technology assistance predominantly to developing countries, and
      establishing clear regulatory guidance on pathways for approval are necessary to
      ensure timely production and equitable distribution.

PMID- 23152677
TI  - Effects of electroacupuncture on recent stroke inpatients with incomplete bladder
      emptying: a preliminary study.
AB  - BACKGROUND: Incomplete bladder emptying (IBE) is defined as having a postvoid
      residual (PVR) urine volume greater than 100 mL for 2 consecutive days. IBE is
      common in stroke patients and could necessitate indwelling or intermittent
      catheterization. The condition is correlated with urinary tract infections, which
      could impede rehabilitation progress and increase medical costs. Treatment for
      patients with IBE includes bladder retraining, biofeedback, medication, and
      botulinum toxin injection, but none of these interventions are completely
      effective. METHODS: All patients with acute stroke who were admitted to the
      rehabilitation ward between August 2010 and April 2011 were included in the study
      and their PVR urine volume was checked. Electroacupuncture (EA; 1 Hz, 15 minutes)
      was performed on the acupoints Sanyinjiao (SP6), Ciliao (BL32), and Pangguangshu
      (BL28) of stroke patients with IBE for a total of ten treatments (five times a
      week for 2 weeks). Bladder diaries, which included the spontaneous voiding and
      PVR urine volumes, were recorded during the course of treatment. RESULTS: The
      presence of IBE was not related to sex, history of diabetes mellitus, stroke type
      (hemorrhagic or ischemic), or stroke location (P > 0.05). Among the 49 patients
      in the study, nine (18%) had IBE, and seven of the stroke patients with IBE were
      treated with EA. Increased spontaneous voiding volume and decreased PVR urine
      volume were noted after ten sessions of EA. CONCLUSION: EA may have beneficial
      effects on stroke survivors with IBE, thereby making it a potential safe modality
      with which to improve urinary function.

PMID- 23152678
TI  - Modified supracricoid laryngectomy: oncological and functional outcomes in the
      elderly.
AB  - BACKGROUND: Supracricoid laryngectomy is an organ preservation surgical technique
      for early-stage glottic tumors. Modified supracricoid laryngectomy using
      sternohyoid muscles for neoglottis reconstruction is a new surgical technique.
      This report evaluates oncological and functional outcomes of this new technique
      and its feasibility in elderly patients. METHODS: Clinical records from 21
      consecutive patients affected by glottic cancer and treated by modified SCL
      between 2004 and 2009 were retrospectively reviewed. Postoperative parameters and
      quality of voice after modified SCL were retrospectively reviewed. Actuarial
      overall survival, disease-specific survival rates, and recurrence-free survival
      rates were assessed. The functional and oncological outcomes of patients over 65
      years were compared with those of patients younger than 65 years of age. RESULTS:
      There were no postoperative complications and all of the patients had complete
      swallowing rehabilitation. Twenty of the 21 patients had decannulation. Two
      patients received total laryngectomy for locoregional relapse. Overall survival
      and disease-specific survival rates were 100%. Recurrence-free survival rates
      were 90.1% and 90% in patients younger and older than 65 years of age,
      respectively. The larynx preservation index was lower in patients who were older
      than 65 years of age. The postoperative courses with regard to functional outcome
      and voice quality in elderly patients were similar to those of patients younger
      than 65 years of age. CONCLUSION: Modified SCL is a new open organ preservation
      surgical technique that is oncologically safe. The positive functional and
      oncological outcomes of this surgical procedure allow it to be performed in
      elderly patients.

PMID- 23152679
TI  - Physical inactivity in COPD and increased patient perception of dyspnea.
AB  - OBJECTIVE: To study patients' levels of exercise activity and the clinical
      characteristics that relate to physical activity and inactivity among patients
      with chronic obstructive pulmonary disease (COPD). METHODS: A postal
      questionnaire was administered to 719 patients with COPD in 2010; patients were
      recruited from the Helsinki and Turku University Central Hospitals in Finland and
      have been followed since 2005. The questionnaire asked participants about their
      exercise routines and other daily activities, potential restrictions to exercise,
      health-related quality of life, and subjective sensations of dyspnea upon
      exertion. RESULTS: A total of 50% of the participants reported exercising>2 times
      a week throughout the year. The proportion of the exercise inactive patients
      increased in parallel with disease progression, but the participants exhibited
      great variation in the degree of activity as well as in sport choices. Year-round
      activity was better maintained among patients who exercised both indoors and
      outdoors. Training activity was significantly correlated with patients' reported
      subjective dyspnea (r=0.32, P<0.001), health-related quality of life (r=0.25,
      P<0.001), mobility score (r=0.37, P<0.001), and bronchial obstruction (r=0.18,
      P<0.001). Active patients did not differ from inactive patients in terms of sex,
      age, smoking status, somatic comorbidities, or body mass index. Irrespective of
      the level of severity of patients' COPD, the most significant barrier to
      exercising was the subjective sensation of dyspnea. CONCLUSION: When a patient
      with COPD suffers from dyspnea and does not have regular exercise routines, the
      patient will most likely benefit from an exercise program tailored to his or her
      physical capabilities.

PMID- 23152680
TI  - Impact of exacerbations on health care cost and resource utilization in chronic
      obstructive pulmonary disease patients with chronic bronchitis from a
      predominantly Medicare population.
AB  - BACKGROUND: Exacerbations of chronic obstructive pulmonary disease (COPD) lead to
      significant increases in resource utilization and cost to the health care system.
      COPD patients with chronic bronchitis and a history of exacerbations pose an
      additional burden to the system. This study examined health care utilization and
      cost among these patients. METHODS: For this retrospective analysis, data were
      extracted from a large national health plan with a predominantly Medicare
      population. This study involved patients who were aged 40-89 years, had been
      enrolled continuously for 24 months or more, had at least two separate insurance
      claims for COPD with chronic bronchitis (International Classification of
      Diseases, Ninth Revision, Clinical Modification code 491.xx), and had pharmacy
      claims for COPD maintenance medications between January 1, 2007, and March 31,
      2009. Two years of data were examined for each patient; the index date was
      defined as the first occurrence of COPD. Baseline characteristics were obtained
      from the first year of data, with health outcomes tracked in the second year.
      Severe exacerbation was defined by COPD-related hospitalization or death;
      moderate exacerbation was defined by oral or parenteral corticosteroid use.
      Adjusted numbers of exacerbations and COPD-related costs per patient were
      estimated controlling for demographic and clinical characteristics. RESULTS: The
      final study sample involved 8554 patients; mean age was 70.1+/-8.6 years and
      49.8% of the overall population had exacerbation, 13.9% had a severe exacerbation
      only, 29.1% had a moderate exacerbation only, and 6.8% had both a severe and
      moderate exacerbation. COPD-related mean annual costs were $4069 (all figures
      given in US dollars) for the overall population and $6381 for patients with two
      or more exacerbations. All-cause health care costs were $18,976 for the overall
      population and $23,901 for patients with history of two or more exacerbations.
      Severity of exacerbations, presence of cardiovascular disease, diabetes, and long
      term oxygen use were associated with higher adjusted costs. CONCLUSIONS: The
      results indicate that despite treatment with maintenance medications, COPD
      patients continue to have exacerbations resulting in higher costs. New
      medications and disease management interventions are warranted to reduce the
      severity and frequency of exacerbations and the related cost impact of the
      disease.

PMID- 23152681
TI  - Antibacterial and antibiofilm properties of yttrium fluoride nanoparticles.
AB  - Antibiotic resistance has prompted the search for new agents that can inhibit
      bacterial growth. Moreover, colonization of abiotic surfaces by microorganisms
      and the formation of biofilms is a major cause of infections associated with
      medical implants, resulting in prolonged hospitalization periods and patient
      mortality. In this study we describe a water-based synthesis of yttrium fluoride
      (YF(3)) nanoparticles (NPs) using sonochemistry. The sonochemical irradiation of
      an aqueous solution of yttrium (III) acetate tetrahydrate [Y(Ac)(3) .
      (H(2)O)(4)], containing acidic HF as the fluorine ion source, yielded
      nanocrystalline needle-shaped YF(3) particles. The obtained NPs were
      characterized by scanning electron microscopy and X-ray elemental analysis. NP
      crystallinity was confirmed by electron and powder X-ray diffractions. YF(3) NPs
      showed antibacterial properties against two common bacterial pathogens
      (Escherichia coli and Staphylococcus aureus) at a MUg/mL range. We were also able
      to demonstrate that antimicrobial activity was dependent on NP size. In addition,
      catheters were surface modified with YF(3) NPs using a one-step synthesis and
      coating process. The coating procedure yielded a homogeneous YF(3) NP layer on
      the catheter, as analyzed by scanning electron microscopy and energy dispersive
      spectroscopy. These YF(3) NP-modified catheters were investigated for their
      ability to restrict bacterial biofilm formation. The YF(3) NP-coated catheters
      were able to significantly reduce bacterial colonization compared to the uncoated
      surface. Taken together, our results highlight the potential to further develop
      the concept of utilizing these metal fluoride NPs as novel antimicrobial and
      antibiofilm agents, taking advantage of their low solubility and providing
      extended protection.

PMID- 23152682
TI  - Fabrication and in vitro release behavior of a novel antibacterial coating
      containing halogenated furanone-loaded poly(L-lactic acid) nanoparticles on
      microarc-oxidized titanium.
AB  - BACKGROUND: Dental implants have become increasingly common for the management of
      missing teeth. However, peri-implant infection remains a problem, is usually
      difficult to treat, and may lead eventually to dental implant failure. The aim of
      this study was to fabricate a novel antibacterial coating containing a
      halogenated furanone compound, ie, (Z-)-4-bromo-5-(bromomethylene)-2(5H)-furanone
      (BBF)-loaded poly(L-lactic acid) (PLLA) nanoparticles on microarc-oxidized
      titanium and to evaluate its release behavior in vitro. METHODS: BBF-loaded PLLA
      nanoparticles were prepared using the emulsion solvent-evaporation method, and
      the antibacterial coating was fabricated by cross-linking BBF-loaded PLLA
      nanoparticles with gelatin on microarc-oxidized titanium. RESULTS: The BBF-loaded
      PLLA nanoparticles had a small particle size (408 +/- 14 nm), a low
      polydispersity index (0.140 +/- 0.008), a high encapsulation efficiency (72.44%
      +/- 1.27%), and a fine spherical shape with a smooth surface. The morphology of
      the fabricated antibacterial coating showed that the BBF-loaded PLLA
      nanoparticles were well distributed in the pores of the microarc oxidation
      coating, and were cross-linked with each other and the wall pores by gelatin. The
      release study indicated that the antibacterial coating could achieve sustained
      release of BBF for 60 days, with a slight initial burst release during the first
      4 hours. CONCLUSION: The novel antibacterial coating fabricated in this study is
      a potentially promising method for prevention of early peri-implant infection.

PMID- 23152683
TI  - Enhancing microparticle internalization by nonphagocytic cells through the use of
      noncovalently conjugated polyethyleneimine.
AB  - Development of micro- and nanotechnology for the study of living cells,
      especially in the field of drug delivery, has gained interest in recent years.
      Although several studies have reported successful results in the internalization
      of micro- and nanoparticles in phagocytic cells, when nonphagocytic cells are
      used, the low internalization efficiency represents a limitation that needs to be
      overcome. It has been reported that covalent surface modification of micro- and
      nanoparticles increases their internalization rate. However, this surface
      modification represents an obstacle for their use as drug-delivery carriers. For
      this reason, the aim of the present study was to increase the capability for
      microparticle internalization of HeLa cells through the use of noncovalently
      bound transfection reagents: polyethyleneimine (PEI) LipofectamineTM 2000 and
      FuGENE 6((r)). Both confocal microscopy and flow cytometry techniques allowed us
      to precisely quantify the efficiency of microparticle internalization by HeLa
      cells, yielding similar results. In addition, intracellular location of
      microparticles was analyzed through transmission electron microscopy and confocal
      microscopy procedures. Our results showed that free PEI at a concentration of
      0.05 mM significantly increased microparticle uptake by cells, with a low
      cytotoxic effect. As determined by transmission electron and confocal microscopy
      analyses, microparticles were engulfed by plasma-membrane projections during
      internalization, and 24 hours later they were trapped in a lysosomal compartment.
      These results show the potential use of noncovalently conjugated PEI in
      microparticle internalization assays.

PMID- 23152684
TI  - Update on extended release quetiapine fumarate in schizophrenia and bipolar
      disorders.
AB  - The atypical antipsychotic quetiapine fumarate is available both as an immediate
      release (IR) and as an extended release (XR) formulation allowing flexibility of
      dosing for individual patients. Approved uses of quetiapine XR include the
      treatment of schizophrenia (including maintenance therapy for prevention of
      relapse), the treatment of bipolar disorder (manic and depressive episodes), and
      the prevention of recurrence in patients with bipolar disorder who respond to
      quetiapine XR. This narrative review provides an update on quetiapine XR in these
      indications. The pharmacological profile of quetiapine, including a moderate
      affinity for dopamine D(2) receptors and higher affinity for serotonin 5
      hydroxytryptophan (5-HT)(2A) receptors, may explain its broad efficacy and low
      propensity for extrapyramidal symptoms (EPS). The XR formulation has similar
      bioavailability but prolonged plasma levels compared with the IR formulation,
      allowing for less frequent (once-daily) dosing. Clinical studies have confirmed
      the efficacy of quetiapine XR in relieving the acute symptoms of schizophrenia
      during short-term trials, and reducing the risk for relapse in long-term studies.
      Direct switching from the IR formulation to the same dose of the XR formulation
      did not reveal any loss of efficacy or tolerability issues, and switching
      patients to quetiapine XR from conventional or other atypical antipsychotics (for
      reasons of insufficient efficacy or tolerability) also proved to be beneficial
      and generally well tolerated. In bipolar disorder, quetiapine XR has also proven
      effective in relieving acute depressive and manic symptoms. Adverse events with
      quetiapine XR in patients with either schizophrenia or bipolar disorder are
      similar to those associated with the IR formulation, the most common being
      sedation, dry mouth, somnolence, dizziness, and headache. The low propensity for
      EPS is maintained with the XR formulation. Overall, evidence from clinical trials
      suggests that quetiapine XR is an effective and generally well-tolerated
      treatment option in patients with schizophrenia and bipolar disorder.

PMID- 23152685
TI  - Surgery for colorectal cancer in the small town of Komotini.
AB  - BACKGROUND: Here we report our experience in treating colon cancer in the 5 years
      from 200 to 2011. Our surgical clinic treated 49 patients with colorectal cancer,
      of whom 28 (57.14%) were men of mean age 62 years and 21 (42.86%) were women of
      mean age 66 years. METHODS: In 15 cases, the cancer was related to the rectum
      (30.61%) and the remaining 34 cases (69.39%) were related to the colon. We found
      synchronous cancer in two patients. One was found in the blank and the upper
      right while the second was found in the transverse and sigmoid colon. Six of our
      patients suffered from coexisting biliary lithiasis and underwent simultaneous
      cholecystectomy, and simultaneous bile duct exploration for common bile duct
      lithiasis was performed in one of these patients. RESULTS: Twenty-eight of the
      patients with colon cancer were treated surgically on an emergency basis. There
      were two postoperative deaths due to septic shock and multiple organ failure. In
      total, we noted seven complications, all of which involved patients who had
      undergone emergency surgery. The length of hospital stay was 8-14 days. Four
      patients with stage IV disease died 2 years after surgery, and the remainder are
      still alive. CONCLUSION: We conclude that colon cancer still occurs after the
      sixth decade, with a male predominance, and is mainly located in the rectum and
      sigmoid colon. The high rate of ileus in our region indicates inadequate
      diagnostic access for the residents of our region. However, mortality remains
      low.

PMID- 23152686
TI  - Barriers to effective diagnosis and management of a bleeding patient with
      undiagnosed bleeding disorder across multiple specialties: results of a
      quantitative case-based survey.
AB  - BACKGROUND: Bleeding symptoms commonly seen by multiple physician specialties may
      belie undiagnosed congenital or acquired bleeding disorders. Acquired hemophilia
      is a potentially life-threatening cause of unexplained acute bleeding manifested
      by an abnormal activated partial thromboplastin time (aPTT) that does not correct
      with 1:1 mixing with normal plasma. METHODS: Practicing physicians
      (hematology/oncology, emergency medicine, geriatrics, internal medicine,
      rheumatology, obstetrics and gynecology, critical care medicine, and general
      surgery) completed an online survey based on a hypothetical case scenario.
      RESULTS: Excluding surgeons and obstetrician/gynecologist respondents, 302
      physicians (about 50 per specialty) were presented with an older adult woman
      complaining of recurrent epistaxis. Nearly 90% ordered a complete blood count and
      coagulation studies (aPTT, prothrombin time [PT]/international normalized ratio
      [INR]). Despite a prolonged aPTT of 42 seconds, <50% of nonhematologists would
      repeat the aPTT, and <45% would consult a hematologist; emergency medicine
      physicians were least likely (10%) and rheumatologists were most likely (43%) to
      consult. After presentation weeks later with bruising and abdominal/back pain,
      >=90% of physicians within each specialty ordered a complete blood count or
      PT/INR/aPTT. Despite an aPTT of 63 seconds, the majority did not repeat the aPTT.
      At this point, approximately 75% of internal medicine and geriatric physicians
      indicated they would consult a hematologist, versus 47% in emergency medicine and
      50% in critical care. All participants preferred abdominal computed tomography
      (80%-84%). After 12 hours of additional observation, 73% to 94% of respondents
      consulted a hematologist. Complete blood count revealed anemia and an aPTT twice
      the upper limit of normal; emergency medicine physicians remained least likely to
      request a consult. CONCLUSION: Determining the cause of an abnormal coagulation
      study result should carry equal weight as looking for the site of bleeding and
      could be facilitated by consultation with a hematologist. Insight from this
      survey highlights knowledge and practice gaps that could be the target of focused
      educational initiatives.

PMID- 23152687
TI  - Adolescent boys with asthma - a pilot study on embodied gendered habits.
AB  - PURPOSE: Asthma is a common chronic disease with gender differences in terms of
      severity and quality of life. This study aimed to understand the gendered
      practices of male asthmatic adolescents in terms of living with and managing
      their chronic disease. The study applied a sociological perspective to identify
      the gender-related practices of participants and their possible consequences for
      health and disease. PATIENTS AND METHODS: The study used a combined
      ethnomethodology and grounded theory design, which was interpreted using
      Bourdieu's theory of practice. We aimed to discover how participants interpreted
      their social worlds to create a sense of meaning in their everyday lives. The
      study was based on multistage focus group interviews with five adolescent
      participants at a specialist center for asthmatic children and youths. We took
      necessary precautions to protect the participants, according to the principles of
      the Declaration of Helsinki. The study protocol was approved by the Regional
      Committee for Medical Research Ethics and the hospital's research department.
      RESULTS: The core concept for asthmatic male adolescents was being men. They were
      focused on being nonasthmatic, and exhibited ambivalence towards the principles
      of the health services. Physical activity supported their aim of being men and
      being nonasthmatic, as well as supported their treatment goals. Being fearless,
      unconcerned, "cool," and dependent also supported the aim of being men and being
      nonasthmatic, but not the health service principle of regular medication.
      Occasionally, the participants were asthmatic when they were not able to or
      gained no advantages from being nonasthmatic. Their practice of being men
      independently of being asthmatic emphasized their deeply gendered habits.
      CONCLUSION: Understanding gender differences in living with and managing asthma
      is important for health workers. Knowledge of embodied gendered habits and their
      reproduction in social interactions and clinical work should be exploited as a
      resource during the supervision of asthmatic adolescent boys.

PMID- 23152688
TI  - Extramedullary plasmacytoma in the presence of multiple myeloma: clinical
      correlates and prognostic relevance.
AB  - OBJECTIVE: We studied the clinical and laboratory features and outcomes of
      multiple myeloma (MM) with extramedullary plasmocytoma (EP) disease both at
      diagnosis and during the course of MM. PATIENTS AND METHODS: Forty-two patients
      of 467 patients with MM were retrospectively analyzed from both the 100th
      Hospital of the People's Liberation Army and Shanghai Changzheng Hospitals. The
      clinical characteristics, laboratory parameters, responses, risk factors, and
      outcomes were analyzed. RESULTS: The median age was 53 years with a male/female
      sex ratio of 34:8. Twenty-six patients had EP disease at the time of diagnosis,
      and 16 patients developed EP during the course of the disease. We found that the
      Durie-Salmon stage, serum lactate dehydrogenase level, beta-2-microglobulin,
      complete blood counts, albumin, and the type of immunoglobulin (Ig) were not
      associated with the development of EP disease. Patients who developed EP during
      the course of MM had a higher ratio of plasmocytes and premature plasmocytes in
      the bone marrow with lower C-reactive protein level and earlier stage of
      International Staging System for Lung Cancer at the diagnosis of MM compared with
      patients who presented with EP at diagnosis. Once the patients developed EP
      disease, they frequently showed resistance to chemotherapy. With a median follow
      up of 30 months, 19 patients were alive. Log-rank univariate analysis showed that
      patients with EP who had normal C-reactive protein, higher hemoglobin, lower
      serum lactate dehydrogenase, and stage I of International Staging System for Lung
      Cancer had longer survival. However, cyclooxygenase multivariate analysis failed
      to show statistical significance for any factor. CONCLUSIONS: EP disease is the
      MM end-phase and is not a rare manifestation of MM with a cumulative incidence of
      9% of MM. The prognosis is very poor once the diagnosis of EP disease is
      concurrent with MM.

PMID- 23152689
TI  - Acute bronchospasm and resolution captured on dynamic CT.
AB  - Computed tomography (CT) imaging provides a noninvasive window beneath the skin,
      defines lung pathology, and facilitates virtual and multimodality fusion
      interventions. A CT scan of acute bronchospasm is shown during a CT-guided lung
      intervention. Dynamic or sequential CT imaging can depict and perhaps even
      quantify acute reversible bronchospasm, and could potentially play a role in
      better understanding pharmacologic interventions for reactive airways and the
      resulting effects.

PMID- 23152690
TI  - Screening strategies and predictive diagnostic tools for the development of new
      onset diabetes mellitus after transplantation: an overview.
AB  - New-onset diabetes mellitus after transplantation (NODAT) is a serious and common
      complication following solid organ transplantation. NODAT has been reported in 2%
      to 53% of all solid organ transplants. Kidney transplant recipients who develop
      NODAT have variably been reported to be at increased risk of fatal and nonfatal
      cardiovascular events and other adverse outcomes including infection, reduced
      patient survival, graft rejection, and accelerated graft loss compared with those
      who do not develop diabetes. Limited clinical studies in liver, heart, and lung
      transplants similarly suggested that NODAT has an adverse impact on patient and
      graft outcomes. Early detection and management of NODAT must, therefore, be
      integrated into the treatment of transplant recipients. Studies investigating the
      best screening or predictive tool for identifying patients at risk for developing
      NODAT early after transplantation, however, are lacking. We review the clinical
      predictive values of fasting plasma glucose, oral glucose tolerance test, and A1C
      in assessing the risk for NODAT development and as a screening tool. Simple
      diabetes prediction models that incorporate clinical and/or metabolic risk
      factors (such as age, body mass index, hypertriglyceridemia, or metabolic
      syndrome) are also presented.

PMID- 23152691
TI  - Health-related quality of life, adiposity, and sedentary behavior in patients
      with early schizophrenia: preliminary study.
AB  - OBJECTIVE: To examine adiposity and sedentary behavior in relation to health
      related quality of life (QoL) in patients with early schizophrenia. METHODS: A
      cross-sectional study was used to assess adiposity by dual-energy X-ray
      absorptiometry scans, habitual physical activity and idle sitting time by the
      Short Form International Physical Activity Questionnaire, and health-related QoL
      by the RAND Medical Outcomes Study SF-36. QoL scores were compared with age
      adjusted Canadian normative population data. RESULTS: There were 36 participants
      with early schizophrenia, average age 25.1 (+/-3.6). Twenty-nine (72.5%) were
      males. Mean illness duration was 30 (+/-18) months, and mean body mass index was
      28.3 (+/-5). Females had higher body fat content than males (30.8 +/-6.9 vs 24.7
      +/- 10.6; t = -2.6, df = 34; P = 0.015). Total body fat (F = 14; P = 0.001), lean
      body mass (F = 10.2; P = 0.001), and sedentary behavior (F = 5; P = 0.013)
      significantly increased across body mass index categories. Total body fat was
      correlated with sedentary behavior (r = 0.62; P = 0.001), and total lean body
      mass was negatively correlated with sedentary behavior (r = 0.39; P = 0.03).
      Based on SF-36 scores, participants had significantly lower physical functioning
      (P = 0.0034), role physical (P = 0.0003), general health (P < 0.0001), vitality
      (P = 0.03), and physical component scores (P = 0.003) than Canadian population
      comparisons. Habitual sedentary behavior, more than activity or adiposity levels,
      was associated with health-related QoL in early schizophrenia. CONCLUSION: Health
      related QoL is lower in early schizophrenia and is predominantly experienced in
      the physical domain. QoL in early schizophrenia relates to sedentary behavior
      more than to activity and adiposity levels.

PMID- 23152692
TI  - Obstructive sleep apnea and bone mineral density in obese patients.
AB  - CONTEXT: Obesity and its co-morbidities may adversely affect bone mineral density
      (BMD). Obstructive sleep apnea (OSA) is a major complication of obesity. To date,
      the effects of OSA on BMD in obese patients have been poorly studied. OBJECTIVE:
      To examine whether the severity of OSA independently correlates with BMD in obese
      patients. METHODS: One hundred and fifteen obese subjects with OSA
      (Apnea/Hypopnea Index [AHI] >=5 events per hour) were included in the study. BMD
      was measured at lumbar spine, total hip, and femoral neck by dual energy X-ray
      absorptiometry. Body mass index, lean mass, and representative measures of
      metabolic syndrome (waist circumference, fasting plasma glucose, blood pressure,
      HDL-cholesterol, triglycerides) and inflammation (ESR, CRP, fibrinogen) were also
      evaluated. RESULTS: BMD did not differ among obese individuals regardless of OSA
      severity. Correlation coefficient analysis for all the covariates showed a lack
      of association between AHI and BMD that was strongly influenced by age and
      weight. CONCLUSION: Our study does not support an independent association between
      AHI and BMD in obese patients. Controlled studies involving a greater number of
      patients are warranted.

PMID- 23152693
TI  - Juvederm((r)) VolbellaTM in the perioral area: a 12-month prospective,
      multicenter, open-label study.
AB  - BACKGROUND: Hyaluronic acid dermal fillers are frequently used for lip
      augmentation, and a new filler has been developed with characteristics especially
      suited for the lips. METHODS: Four European sites treated 60 subjects with
      Juvederm((r)) VolbellaTM injectable gel in the perioral area, and subjects
      returned to the clinic at 1, 3, 6, 9, and 12 months for follow-up. The primary
      effectiveness endpoint established a priori was a Month 3 responder rate on the 4
      point Lip Fullness Scale (LFS) of >=40% and statistically > 0%, where responders
      improved >= 1 point from baseline on the investigator's assessment of LFS. At
      follow-up, subjects assessed lip fullness goal achievement, the look and feel of
      their lips, and their satisfaction with the effects of treatment. RESULTS: The
      Month 3 LFS responder rate was 93.2% (P < 0.0001), so the primary endpoint was
      met, and clinical effectiveness was demonstrated. The responder rate over time
      showed that 78.0% of subjects still had improved lip fullness at Month 9 and
      48.3% at Month 12. After treatment 98.3% of subjects reported that their lip
      fullness goal had been achieved, and this was maintained at 86.4% at Month 9 and
      56.9% at Month 12. At Month 1, 81.0% of subjects reported that their lips felt
      smooth, and 91.4% reported that their lips looked natural (scores of 7-10 on an
      11-point scale, where 0 was an unfavorable outcome and 10 was a favorable
      outcome). Similarly, 96.6% of subjects reported being satisfied (scores between 7
      and 10 on an 11-point scale where 0 = very dissatisfied, 10 = very satisfied) at
      Month 1, and by Month 12 more than 80% of subjects were still satisfied. There
      were no severe adverse events related to treatment. CONCLUSION: Juvederm((r))
      VolbellaTM injectable gel is well tolerated and has been demonstrated to provide
      a smooth and natural improvement in lip fullness that lasts for up to 1 year.

PMID- 23152694
TI  - Emotional benefit of cosmetic camouflage in the treatment of facial skin
      conditions: personal experience and review.
AB  - BACKGROUND: Recent studies highlighting the psychological benefits of medical
      treatment for dermatological skin conditions have demonstrated a clear role for
      medical therapy in psychological health. Skin conditions, particularly those that
      are overtly visible, such as those located on the face, neck, and hands, often
      have a profound effect on the daily functioning of those affected. The literature
      documents significant emotional benefits using medical therapy in conditions such
      as acne, psoriasis, vitiligo, and rosacea, but there is little evidence
      documenting similar results with the use of cosmetic camouflage. Here we present
      a review highlighting the practical use of cosmetic camouflage makeup in patients
      with facial skin conditions and review its implications for psychological health.
      METHODS: A search of the Medline and Scopus databases was performed to identify
      articles documenting the emotional benefit of cosmetic camouflage. RESULTS:
      Cosmetic camouflage provides a significant emotional benefit for patients with
      facial skin conditions, and this is substantiated by a literature review and
      personal experience. More clinical studies are needed to assess and validate the
      findings reported here. CONCLUSION: Patients with visible skin conditions have
      increased rates of depression, anxiety, and decreased self-esteem. It is prudent
      for us to consider therapies that can offer rapid and dramatic results, such as
      cosmetic camouflage.

PMID- 23152695
TI  - Comparing common reasons for inpatient and outpatient visits between commercially
      insured duloxetine or pregabalin initiators with fibromyalgia.
AB  - BACKGROUND: The purpose of this study was to examine the main reasons for
      inpatient or outpatient visits after initiating duloxetine or pregabalin.
      METHODS: Commercially insured patients with fibromyalgia and aged 18-64 years who
      initiated duloxetine or pregabalin in 2006 with 12-month continuous enrollment
      before and after initiation were identified. Duloxetine and pregabalin cohorts
      with similar demographics, pre-index clinical and economic characteristics, and
      pre-index treatment patterns were constructed via propensity scoring
      stratification. Reasons for inpatient admissions, physician office visits,
      outpatient hospital visits, emergency room visits, and primary or specialty care
      visits over the 12 months post-index period were examined and compared. Logistic
      regression was used to assess the contribution of duloxetine versus pregabalin
      initiation to the most common reasons for visits, controlling for cross-cohort
      differences. RESULTS: Per the study design, the duloxetine (n = 3711) and
      pregabalin (n = 4111) cohorts had similar demographics (mean age 51 years, 83%
      female) and health care costs over the 12-month pre-index period. Total health
      care costs during the 12-month post-index period were significantly lower for
      duloxetine patients than for pregabalin patients ($19,378 versus $27,045, P <
      0.05). Eight of the 10 most common reasons for inpatient admissions and
      outpatient hospital (physician office, emergency room, primary or specialty care)
      visits were the same for both groups. Controlling for cross-cohort differences,
      duloxetine patients were less likely to be hospitalized due to an intervertebral
      disc disorder or major depressive disorder, to have a physician office visit due
      to nonspecific backache/other back/neck pain (NB/OB/NP) disorder, or to go to
      specialty care due to a soft tissue, NB/OP/NP, or intervertebral disc disorder.
      However, duloxetine patients were more likely to have a primary care visit due to
      a soft tissue disorder, essential hypertension, or other general symptoms.
      CONCLUSION: Among similar commercially insured patients with fibromyalgia who
      initiated duloxetine or pregabalin, duloxetine patients had significantly lower
      health care costs over the 12-month post-index period. The leading reasons for
      inpatient or outpatient visits were also somewhat different.

PMID- 23152696
TI  - A randomized, multicenter, pilot study comparing the efficacy and safety of a
      bupivacaine-collagen implant (XaraColl((r))) with the ON-Q PainBuster((r)) Post
      op Pain Relief System following open gynecological surgery.
AB  - BACKGROUND: XaraColl((r)), a collagen-based intraoperative implant that delivers
      bupivacaine to the site of surgical trauma, is under development for
      postoperative analgesia. We compared the efficacy and safety of XaraColl for the
      prevention of postsurgical pain versus a slow postoperative perfusion of
      bupivacaine to the wound environment via the ON-Q PainBuster((r)) Post-op Pain
      Relief System (ON-Q). METHODS: We randomized 27 women undergoing open
      gynecological surgery to receive either three XaraColl implants (each containing
      50 mg bupivacaine hydrochloride) or ON-Q (900 mg bupivacaine hydrochloride
      perfused over 72 hours) in a 1:1 ratio. Following surgery, patients had access to
      intravenous morphine via a patient-controlled analgesia pump as rescue analgesia
      for the first 24 hours and to oral opioid medication thereafter. Total use of
      opioid analgesia was compared through 24, 48, 72, and 96 hours after surgery.
      Patients also evaluated overall pain control over the 96-hour period using a five
      point numeric rating scale. Safety was assessed for 30 days after surgery.
      RESULTS: XaraColl was non-inferior to ON-Q in total use of opioid analgesia for
      the first 24, 48, 72, and 96 hours after surgery, with a statistical trend
      towards reduced opioid use in favor of XaraColl over 24, 48, and 72 hours (P =
      0.067, 0.100, and 0.089, respectively). The time to first use of opioid analgesia
      was also significantly delayed in patients treated with XaraColl (P = 0.024).
      There was no significant difference between groups in patients' evaluation of
      pain control or their satisfaction with the treatment in general. Both treatments
      were considered safe and well tolerated. CONCLUSION: Despite using only 17% of
      the ON-Q dose, XaraColl is as effective as ON-Q in providing postoperative
      analgesia for 4 days after open gynecological surgery. These preliminary findings
      suggest that XaraColl offers great potential for the management of postoperative
      pain and warrants further definitive studies.

PMID- 23152697
TI  - Psychological control is a key modulator of fibromyalgia symptoms and
      comorbidities.
AB  - OBJECTIVE: We hypothesized that fibromyalgia (FM) patients would report lower
      levels of psychological control mechanisms and that higher levels of control
      would moderate key symptoms associated with FM, such as pain, fatigue, perceived
      stress, and mood disturbance. METHODS: Ninety-eight women with FM diagnosed
      according to American College of Rheumatology criteria and 35 matched pain-free
      women were identified. Applied questionnaires included the Fibromyalgia Impact
      Questionnaire, Profile of Mood States, Perceived Control of Internal States
      Scale, Perceived Stress Scale, and Mastery Scale. Differences were sought using t
      tests, one-way analysis of variance, bivariate correlations, and multiple
      regression analysis. RESULTS: Comparison between FM patients and healthy
      individuals found significant differences in control (Perceived Control of
      Internal States Scale and Mastery Scale), pain, perceived stress, fatigue,
      confusion, and mood disturbance (all P < 0.001). There were significant
      associations found between both high and low levels of control on stress, mood,
      pain, and fatigue (P < 0.001-0.05). Strong negative correlations were present
      between internal control and perceived stress (P < 0.0005). CONCLUSION: FM
      patients use significantly different control styles compared with healthy
      individuals. Levels and type of psychological control buffer mood, stress,
      fatigue, and pain in FM. Control appears to be an important "up-stream" process
      in FM mechanisms and is amenable to intervention.

PMID- 23152699
TI  - Pain point system scale (PPSS): a method for postoperative pain estimation in
      retrospective studies.
AB  - PURPOSE: Pain rating scales are widely used for pain assessment. Nevertheless, a
      new tool is required for pain assessment needs in retrospective studies. METHODS:
      The postoperative pain episodes, during the first postoperative day, of three
      patient groups were analyzed. Each pain episode was assessed by a visual analog
      scale, numerical rating scale, verbal rating scale, and a new tool - pain point
      system scale (PPSS) - based on the analgesics administered. The type of analgesic
      was defined based on the authors' clinic protocol, patient comorbidities, pain
      assessment tool scores, and preadministered medications by an artificial neural
      network system. At each pain episode, each patient was asked to fill the three
      pain scales. Bartlett's test and Kaiser-Meyer-Olkin criterion were used to
      evaluate sample sufficiency. The proper scoring system was defined by varimax
      rotation. Spearman's and Pearson's coefficients assessed PPSS correlation to the
      known pain scales. RESULTS: A total of 262 pain episodes were evaluated in 124
      patients. The PPSS scored one point for each dose of paracetamol, three points
      for each nonsteroidal antiinflammatory drug or codeine, and seven points for each
      dose of opioids. The correlation between the visual analog scale and PPSS was
      found to be strong and linear (rho: 0.715; P < 0.001 and Pearson: 0.631; P <
      0.001). CONCLUSION: PPSS correlated well with the known pain scale and could be
      used safely in the evaluation of postoperative pain in retrospective studies.

PMID- 23152700
TI  - Use of 5% lidocaine medicated plaster to treat localized neuropathic pain
      secondary to traumatic injury of peripheral nerves.
AB  - OBJECTIVE: The efficacy of 5% lidocaine medicated plaster (LMP) has previously
      been demonstrated in post-traumatic localized neuropathic pain. This study
      evaluated the use of LMP in localized neuropathic pain secondary to traumatic
      peripheral nerve injury. PATIENTS AND METHODS: This prospective observational
      study enrolled patients with traumatic injuries to peripheral nerves that were
      accompanied by localized neuropathic pain of more than 3 months duration.
      Demographic variables, pain intensity (measured using the numeric rating scale;
      NRS), answers to the Douleur Neuropathique 4 (DN4) questionnaire, and the size of
      the painful area were recorded. RESULTS: Nineteen patients were included, aged
      (mean +/- standard deviation) 41.4 +/- 15.7 years. Nerve injuries affected the
      upper (eight patients) or lower (11 patients) limbs. The mean duration of pain
      before starting treatment with LMP was 22.6 +/- 43.5 months (median 8 months).
      Mean baseline values included: NRS 6.7 +/- 1.6, painful area 17.8 +/- 10.4 cm(2)
      (median 18 cm(2)), and DN4 score 6.7 +/- 1.4. The mean duration of treatment with
      LMP was 19.5 +/- 10.0 weeks (median 17.4 weeks). Mean values after treatment
      were: NRS 2.8 +/- 1.5 (>=3 point reduction in 79% of patients, >=50% reduction in
      57.9% of patients) and painful area 2.1 +/- 2.3 cm(2) (median 1 cm(2), >=50%
      reduction in 94.7% of patients). Functional improvement after treatment was
      observed in 14/19 patients (73.7%). CONCLUSION: LMP effectively treated traumatic
      injuries of peripheral nerves which presented with chronic localized neuropathic
      pain, reducing both pain intensity and the size of the painful area.

PMID- 23152701
TI  - Thoracic paravertebral block versus transversus abdominis plane block in major
      gynecological surgery: a prospective, randomized, controlled, observer-blinded
      study.
AB  - BACKGROUND AND OBJECTIVES: Patients undergoing abdominal surgery often receive an
      epidural infusion for postoperative analgesia. However, when epidural analgesia
      is contraindicated or unwanted, the administration of opioids is the usual means
      used to relieve pain. Various regional analgesia techniques used in conjunction
      with systemic analgesia have been reported to reduce the cumulative postoperative
      opioid consumption and opioid-induced side effects. The objective of this trial
      was to assess the effectiveness of transversus abdominis plane block and
      paravertebral block in women undergoing major gynecological surgery. METHODS: We
      analyzed 58 patients scheduled for a midline vertical laparatomy due to
      gynecological cancer. They were all equipped with a patient-controlled
      postoperative analgesia pump that delivered ketobemidon. In addition, some
      patients were randomized to receive either a bilateral transversus abdominis
      plane block (n = 19) or a bilateral paravertebral block at the level of Th10 (n =
      19). Both blocks were performed preoperatively as a single injection of
      bupivacaine. RESULTS: Cumulative ketobemidon consumption, postoperative pain
      scores at rest and while coughing, and postoperative nausea and vomiting scores
      were assessed by a blinded observer at 2, 4, 6, 24, and 48 hours postoperatively.
      Both blocks were associated with significant reductions in opioid consumption and
      pain scores throughout the study period compared with the control patients.
      Postoperative nausea and vomiting scores were low in all groups, but during the
      early postoperative period more control group patients needed antiemetics.
      CONCLUSION: Both methods of inducing block can serve as effective analgesia
      adjuncts in women undergoing major gynecological surgery. Although thoracic
      paravertebral block appeared to be more effective than transversus abdomins
      block, the latter performed under ultrasound guidance seems to be a more
      controlled and safe alternative.

PMID- 23152698
TI  - Chronic postsurgical pain: still a neglected topic?
AB  - BACKGROUND: Surgical injury can frequently lead to chronic pain. Despite the
      obvious importance of this problem, the first publications on chronic pain after
      surgery as a general topic appeared only a decade ago. This study tests the
      hypothesis that chronic postsurgical pain was, and still is, represented
      insufficiently. METHODS: We analyzed the presentation of this topic in journal
      articles covered by PubMed and in surgical textbooks. The following signs of
      insufficient representation in journal articles were used: (1) the lack of
      journal editorials on chronic pain after surgery, (2) the lack of journal
      articles with titles clearly indicating that they are devoted to chronic
      postsurgical pain, and (3) the insufficient representation of chronic
      postsurgical pain in the top surgical journals. RESULTS: It was demonstrated that
      insufficient representation of this topic existed in 1981-2000, especially in
      surgical journals and textbooks. Interest in this topic began to increase,
      however, mostly regarding one specific surgery: herniorrhaphy. It is important
      that the change in the attitude toward chronic postsurgical pain spreads to other
      groups of surgeries. CONCLUSION: Chronic postsurgical pain is still a neglected
      topic, except for pain after herniorrhaphy. The change in the attitude toward
      chronic postsurgical pain is the important first step in the approach to this
      problem.

PMID- 23152703
TI  - Breast imaging reports for malignant lesions: are we maintaining recommended BI
      RADS((r)) lexicon standards?
AB  - BACKGROUND: The purpose of this study was to evaluate mammography reports for
      diagnosed breast cancer cases in major government and private centers in Karachi,
      Pakistan, with respect to concordance with the Breast Imaging Reports And Data
      System (BI-RADS((r))) lexicon. METHODS: A prospective, descriptive, multicenter
      study was conducted in the radiology sections of the Aga Khan University
      Hospital, Pakistan Naval Station Shifa Hospital, Advanced Radiology Clinic,
      Karachi Institute of Radiotherapy and Nuclear Medicine, and Civil Hospital
      Karachi between May and October 2010 after approval from the ethical review
      committee of Aga Khan University. Mammograms reported as BI-RADS category 4 and 5
      were included in the study. Mammograms reported as BI-RADS category 0, 1, 2 and 3
      were excluded. Fifty reports were collected from each center. Data were collected
      about the clinical indication, breast density, location and description of the
      lesion, calcification, and comments on axillary lymph nodes. This description was
      compared with the BI-RADS lexicon. RESULTS: The mean age of the patients was 50
      +/- 12 years. The clinical indication, breast parenchymal density, lesion
      location, and presence of calcification were better described by the private
      centers, while description of lymph node status was better stated by the
      government centers. This difference was statistically significant, except for
      lesion description. The description of masses by the two reporting groups was
      comparable. CONCLUSION: Mammographic reporting of malignant breast lesions in the
      private sector is more in line with the BI-RADS lexicon, as compared with
      government sector hospitals in Karachi, Pakistan. Lymph node documentation was
      better in government sector reports.

PMID- 23152702
TI  - Current treatment options for the management of esophageal cancer.
AB  - In recent years, esophageal cancer characteristics and management options have
      evolved significantly. There has been a sharp increase in the frequency of
      esophageal adenocarcinoma and a decline in the frequency of squamous cell
      carcinoma. A more comprehensive understanding of prognostic factors influencing
      outcome has also been developed. This has led to more management options for
      esophageal cancer at all stages than ever before. A multidisciplinary, team
      approach to management in a high volume center is the preferred approach. Each
      patient should be individually assessed based on type of cancer, local or
      regional involvement, and his or her own functional status to determine an
      appropriate treatment regimen. This review will discuss management of esophageal
      cancer relative to disease progression and patient functional status.

PMID- 23152704
TI  - Measures of risk and their relationship to the relative size of a high-risk
      group: application to medical thromboprophylaxis.
AB  - BACKGROUND: The aim of this study was to establish the meaning of "high-risk"
      when the subgroup so defined by risk factor analysis is a substantial proportion
      of the population. This is clinically important when patients, deemed to be at
      high risk as a result of risk factor analysis, become eligible for a clinical
      intervention to decrease the risk, especially if the intervention has adverse
      effects. One example in clinical practice is the assessment of eligibility for
      medical thromboprophylaxis. METHODS: Equations were derived relating risk and the
      proportion of the population (F) deemed to be at high risk on risk factor
      analysis, based on the formula for weighted average. The equations were validated
      for the population of medical inpatients at high- or low-risk of thromobembolic
      events using a spreadsheet model of thrombosis risk containing known risk factors
      for venous thromboembolism in this population. RESULTS: The validated equations
      define an upper limit of absolute and incremental risk (risk relative to the
      whole population) in the high-risk group that is a function of or equal to 1/F,
      respectively. The added risk in the high-risk group declines to zero as F tends
      to 1, because it must be balanced by the diminishing risk in the progressively
      smaller low-risk group while maintaining the population average. CONCLUSION: The
      results of this study have implications for the validity of the published
      eligibility criteria for medical thromboprophylaxis.

PMID- 23152706
TI  - The Danish national type 2 diabetes cohort - the DD2 study.

PMID- 23152705
TI  - Survival after liver resection in metastatic colorectal cancer: review and meta
      analysis of prognostic factors.
AB  - BACKGROUND: Hepatic metastases develop in approximately 50% of colorectal cancer
      (CRC) cases. We performed a review and meta-analysis to evaluate survival after
      resection of CRC liver metastases (CLMs) and estimated the summary effect for
      seven prognostic factors. METHODS: Studies published between 1999 and 2010,
      indexed on Medline, that reported survival after resection of CLMs, were
      reviewed. Meta-relative risks for survival by prognostic factor were calculated,
      stratified by study size and annual clinic volume. Cumulative meta-analysis
      results by annual clinic volume were plotted. RESULTS: Five- and 10-year survival
      ranged from 16% to 74% (median 38%) and 9% to 69% (median 26%), respectively,
      based on 60 studies. The overall summary median survival time was 3.6 (range: 1.7
      7.3) years. Meta-relative risks (95% confidence intervals) by prognostic factor
      were: node positive primary, 1.6 (1.5-1.7); carcinoembryonic antigen level, 1.9
      (1.1-3.2); extrahepatic disease, 1.9 (1.5-2.4); poor tumor grade, 1.9 (1.3-2.7);
      positive margin, 2.0 (1.7-2.5); >1 liver metastases, 1.6 (1.4-1.8); and >3 cm
      tumor diameter, 1.5 (1.3-1.8). Cumulative meta-analyses by annual clinic volume
      suggested improved survival with increasing volume. CONCLUSION: The overall
      median survival following CLM liver resection was 3.6 years. All seven
      investigated prognostic factors showed a modest but significant predictive
      relationship with survival, and certain prognostic factors may prove useful in
      determining optimal therapeutic options. Due to the increasing complexity of
      surgical interventions for CLM and the inclusion of patients with higher disease
      burdens, future studies should consider the potential for selection and referral
      bias on survival.

PMID- 23152707
TI  - Limitations of widely used high-risk human papillomavirus laboratory-developed
      testing in cervical cancer screening.
AB  - OBJECTIVE: To increase awareness of the limitations of high-risk human
      papillomavirus (hrHPV) laboratory-developed testing (LDT) widely used in US
      cervical cancer screening. METHODS AND RESULTS: A young woman in her 30s was
      diagnosed and treated for stage 1B1 cervical squamous cell carcinoma in which HPV
      16 DNA was detected using polymerase chain reaction testing. Both 1 month before
      and 42 months before cervical cancer diagnosis, the patient had highly abnormal
      cytology findings; however, residual SurePathTM (Becton, Dickson and Company,
      Franklin Lakes, NJ) vial fluid yielded negative Hybrid Capture 2 (HC2; Qiagen NV,
      Hilden, Germany) hrHPV LDT results from each of the two specimens. This prompted
      questions to be asked concerning the performance characteristics of hrHPV LDT. A
      review of the available data indicates that (1) purification of DNA from SurePath
      specimens requires complex sample preparation due to formaldehyde crosslinking of
      proteins and nucleic acids, (2) HC2-SurePath hrHPV testing had not been Food and
      Drug Administration-approved after multiple premarket approval submissions, (3)
      detectible hrHPV DNA in the SurePath vial decreases over time, and (4) US
      laboratories performing HC2-SurePath hrHPV LDT testing are not using a
      standardized manufacturer-endorsed procedure. CONCLUSION: Recently updated
      cervical screening guidelines in the US recommend against the use of hrHPV LDT in
      cervical screening, including widely used HC2 testing from the SurePath vial. The
      manufacturer recently issued a technical bulletin specifically warning that use
      of SurePath samples with the HC2 hrHPV test may provide false negative results
      and potentially compromise patient safety. Co-collection using a Food and Drug
      Administration-approved hrHPV test medium is recommended for HPV testing of
      patients undergoing cervical screening using SurePath samples.

PMID- 23152708
TI  - Protection of bone in premenopausal women with breast cancer: focus on zoledronic
      acid.
AB  - Maintaining bone health is important for patients with breast cancer (BC), the
      most commonly diagnosed cancer in American women. Indeed, bone loss is common
      throughout the BC disease continuum. In the metastatic BC setting, patients are
      likely to develop bone metastases, a painful complication that can lead to
      potentially debilitating skeletal-related events. Bone health is equally
      important for patients with early BC. During adjuvant therapy for early BC, the
      largest challenge to bone health is from accelerated bone mineral density (BMD)
      loss. Although decreased BMD is well recognized in older, postmenopausal women,
      it may be underestimated in younger, premenopausal women undergoing endocrine
      therapy for BC. The rate and extent of cancer therapy-induced bone loss (from
      chemotherapy or endocrine therapy) are substantially greater than normal
      decreases in BMD during menopause. Bisphosphonates such as zoledronic acid (ZOL)
      are antiresorptive agents indicated for the treatment of bone metastases from BC.
      Clinical trials over the past few years suggest that, although not yet approved
      for this indication, ZOL can prevent cancer therapy-induced bone loss and improve
      BMD in premenopausal women receiving adjuvant (endocrine or chemo-) therapy for
      BC. Furthermore, the benefits of ZOL therapy may go beyond maintaining bone
      health and include potential anticancer benefits together with favorable
      tolerability and cost/benefit profiles. This review will focus specifically on
      the role of ZOL in preserving the bone health of premenopausal women with BC.

PMID- 23152709
TI  - Violence permeating daily life: a qualitative study investigating perspectives on
      violence among women in Karachi, Pakistan.
AB  - BACKGROUND: This study explored how married women perceive situations which
      create family conflicts and lead to different forms of violence in urban
      Pakistan. In addition, it examines perceptions of consequences of violence, their
      adverse health effects, and how women resist violence within marital life.
      METHODS: Five focus group discussions were conducted with 28 women in Karachi.
      Purposive sampling, aiming for variety in age, employment status, education, and
      socioeconomic status, was employed. The focus group discussions were conducted in
      Urdu and translated into English. Manifest and latent content analysis were
      applied. RESULTS: One major theme emerged during the analysis, ie, family
      violence through the eyes of females. This theme was subdivided into three main
      categories. The first category, ie, situations provoking violence and their
      manifestations, elaborates on circumstances that provoke violence and situations
      that sustain violence. The second category, ie, actions and reactions to exposure
      to violence, describes consequences of ongoing violence within the family,
      including those that result in suicidal thoughts and actions. The final category,
      ie, resisting violence, describes how violence is avoided through women's
      awareness and actions. CONCLUSION: The current study highlights how female
      victims of abuse are trapped in a society where violence from a partner and
      family members is viewed as acceptable, where divorce is unavailable to the
      majority, and where societal support of women is limited. There is an urgent need
      to raise the subject of violence against women and tackle this human rights
      problem at all levels of society by targeting the individual, family, community,
      and societal levels concurrently.

PMID- 23152711
TI  - RX Herculink Elite((r)) renal stent system: a review of its use for the treatment
      of renal artery stenosis.
AB  - The management of renal artery stenosis (RAS) remains controversial. While some
      evidence suggests that treatment with stent placement is beneficial, randomized
      trials have failed to demonstrate a significant benefit. Ongoing clinical trials
      should help to better define the role for stenting of RAS while avoiding
      limitations seen with earlier trials. When it comes to stenting for RAS, several
      stents have been used; however, many stents which have been used previously and
      which are still being used are biliary stents that are used "off-label." These
      stents have typically come onto the market through the 510(k) pathway. To date, a
      total of five stents have been approved by the United States Food and Drug
      Administration for use in the renal arteries. Of the five stents that have
      received approval, the BridgeTM Extra Support (Medtronic Cardio- Vascular, Santa
      Rosa, CA) and the Palmaz((r)) (Cordis Corporation, Bridgewater, NJ) stents are no
      longer available. Currently, the Express((r)) SD (Boston Scientific, Natick, MA),
      FormulaTM (Cook Medical, Bloomington, IN), and Herculink Elite((r)) (Abbott
      Vascular, Santa Clara, CA) stents are Food and Drug Administration approved and
      available for use. The Herculink Elite is the most recently approved of the renal
      stents, having received approval in late 2011. The Herculink Elite stent is the
      only cobalt chromium stent approved for use in the renal arteries. Although trial
      data are limited and direct comparisons among renal stents is not possible, the
      Herculink Elite stent has demonstrated good performance. Additionally, the design
      of the Herculink Elite offers some advantages that may translate into improved
      outcomes.

PMID- 23152710
TI  - Neuromodulation therapies and treatment-resistant depression.
AB  - BACKGROUND: Patients with treatment-resistant depression (TRD) who showed partial
      response to pharmacological and psychotherapeutic interventions need a trial of
      neuromodulation therapies (NTs). OBJECTIVE: This paper aims to review evidence
      based data on the use of NTs in TRD. METHOD: Using keywords and combined-word
      strategy, multiple computer searches of PubMed, Google Scholar, Quertle(R), and
      Medline were conducted for retrieving relevant articles published in English
      language peer-reviewed journals (2000-2012). Those papers that addressed NTs in
      TRD were retained for extensive review. RESULTS: Despite methodological
      challenges, a range of 30%-93% of TRD patients showed substantial improvement to
      one of the NTs. One hundred-percent improvement was reported in two single-case
      studies on deep brain stimulation. Some studies reported no benefits from
      transcranial direct current stimulation. NTs were reported to have good clinical
      efficacy, better safety margin, and benign side-effect profile. Data are limited
      regarding randomized clinical trials, long-term efficacy, and cost-effectiveness
      of these approaches. Both modified electroconvulsive therapy and magnetic seizure
      therapy were associated with reversible but disturbing neurocognitive adverse
      effects. Besides clinical utility, NTs including approaches on the horizon may
      unlock the biological basis underlying mood disorders including TRD. CONCLUSION:
      NTs are promising in patients with TRD, as the majority of them show good
      clinical response measured by standardized depression scales. NTs need further
      technological refinements and optimization together with continuing well-designed
      studies that recruit larger numbers of participants with TRD.

PMID- 23152712
TI  - Mometasone implant for chronic rhinosinusitis.
AB  - The Propel mometasone-eluting stent (Intersect ENT, Palo Alto, CA) is the first
      Food and Drug Administration-approved device for delivering steroid medication
      into the ethmoid cavity following surgery. The implant is composed of a
      biodegradable polymer in a lattice pattern that expands in a spring-like fashion
      to conform to the walls of a dissected ethmoid cavity and contains a total of 370
      MUg of mometasone furoate designed for gradual release over 30 days. The purpose
      of this article is to review the mode of action and the evidence supporting the
      efficacy of this novel technology. Three recently published clinical trials have
      demonstrated that the mometasone-eluting stent produced statistically significant
      reductions in inflammation, polyp formation, and postoperative adhesions. In
      addition, the implant has been found to significantly reduce the need for
      postoperative administration of oral steroids and to decrease the frequency of
      postoperative lysis of adhesions. Minimal adverse effects were reported in these
      trials and included infection, crusting, and granulation tissue formation.
      Although the placement of steroid-impregnated packing, stents, sponges, and gels
      has previously been used in the postoperative sinus cavities, the Propel
      mometasone-eluting stent introduces a new mechanism for localized and controlled
      delivery of topical therapy directly to the nasal mucosa for chronic
      rhinosinusitis.

PMID- 23152713
TI  - Investigating the role of combined acoustic-visual feedback in one-dimensional
      synchronous brain computer interfaces, a preliminary study.
AB  - Feedback plays an important role when learning to use a brain computer interface
      (BCI), particularly in the case of synchronous feedback that relies on the
      interaction subject. In this preliminary study, we investigate the role of
      combined auditory-visual feedback during synchronous MU rhythm-based BCI sessions
      to help the subject to remain focused on the selected imaginary task. This new
      combined feedback, now integrated within the general purpose BCI2000 software,
      has been tested on eight untrained and three trained subjects during a
      monodimensional left-right control task. In order to reduce the setup burden and
      maximize subject comfort, an electroencephalographic device suitable for dry
      electrodes that required no skin preparation was used. Quality and index of
      improvement was evaluated based on a personal self-assessment questionnaire from
      each subject and quantitative data based on subject performance. Results for this
      preliminary study show that the combined feedback was well tolerated by the
      subjects and improved performance in 75% of the naive subjects compared with
      visual feedback alone.

PMID- 23152714
TI  - New bipolar tissue ligator combines constant tissue compression and temperature
      guidance: histologic study and implications for treatment of hemorrhoids.
AB  - BACKGROUND: Several minimally invasive technologies are available to treat common
      soft tissue lesions including symptomatic hemorrhoids. The use of energy to
      deliver heat and coagulate target lesions is commonly practiced. This study
      compares the histologic effects produced on intestinal tissues by two energy
      based systems which employ different approaches of heat delivery. METHODS: TWO
      HEAT DELIVERY SYSTEMS WERE EVALUATED IN VIVO IN A SINGLE PORCINE SUBJECT:
      infrared coagulator and bipolar tissue ligator utilizing constant tissue
      compression and temperature guidance. Eighteen treatment sites divided into three
      groups of six were assessed. Treatment site temperature was measured and the
      effects of thermal treatment in the mucosa, submucosa, submucosal vessels, and
      muscularis layer were scored. Lateral thermal spread beyond the energy
      application site was also assessed. RESULTS: Treatment site temperatures were
      much lower in the bipolar ligator group than in the infrared coagulator group.
      The mucosal and submucosal tissue changes observed in tissues treated with
      infrared energy and bipolar energy at 55 degrees C were similar. Both the mucosal
      and submucosal tissue changes with bipolar energy at 50 degrees C were
      significantly less. CONCLUSION: Both devices achieved similar histologic results.
      However, the unique design of the bipolar ligator, which allows consistent
      capture, constant compression, and temperature monitoring of target tissue,
      accomplished the desired histologic changes with less muscular damage at much
      lower temperatures than the infrared coagulator. The use of bipolar ligation
      could offer clinical advantages such as reduced patient pain and a minimized
      chance of heat-related collateral tissue damage.

PMID- 23152715
TI  - Psychometric properties of the Norwegian version of the General Health
      Questionnaire (GHQ-30) among older people living at home.
AB  - INTRODUCTION: The incidence and prevalence of mental problems among older people
      are difficult to map because the causes are often complex and the symptoms
      manifest in a range of ways. Therefore, there is a need for robust and useful
      instruments for screening mental problems in this group. One instrument used in
      Norway and around the world is the 30-item version of the General Health
      Questionnaire (GHQ-30). Nevertheless, studies testing reliability and validity of
      the Norwegian version are scarce. AIM: The aim of this study was to test the
      psychometric properties, by means of reliability and construct validity, of the
      Norwegian version of the GHQ-30 in a sample of older people living at home.
      METHODS: A cross-sectional design was used. A postal questionnaire including
      background variables and a range of health related questions, including the GHQ
      30, was mailed to 6033 older people (age 65 years or more) who lived in their own
      homes in southern Norway. A final sample of 2106 persons (34.9%) responded to and
      returned the questionnaire. Data were analyzed statistically regarding
      reliability and construct validity of the GHQ-30. RESULTS: The reliability of the
      instrument, reflecting its homogeneity, was shown in a Cronbach's alpha
      coefficient of 0.93 and in significant item-to-total correlations. Construct
      validity was supported as the GHQ-30 demonstrated robustness in separating groups
      with known mental problems. Construct validity was also demonstrated in a logical
      four factor solution, which accounted for 50.0% of the variance in the study
      group. The factor structure supported previous testing studies of the instrument.
      CONCLUSION: The GHQ-30 showed satisfactory psychometric properties regarding
      reliability and construct validity in this study group, which may indicate that
      the instrument is suitable for use in screening mental problems in older people
      living at home.

PMID- 23152716
TI  - Clinical and economic outcomes after surgical aortic valve replacement in
      Medicare patients.
AB  - BACKGROUND: Aortic valve replacement (AVR) is the standard of care for patients
      with severe, symptomatic aortic stenosis who are suitable surgical candidates,
      benefiting both non-high-risk and high-risk patients. The purpose of this study
      was to report long-term medical resource use and costs for patients following AVR
      and validate our assumption that high-risk patients have worse outcomes and are
      more costly than non-high-risk patients in this population. METHODS: Patients
      with aortic stenosis who underwent AVR were identified in the 2003 Medicare 5%
      Standard Analytic Files and tracked over 5 years to measure clinical outcomes,
      medical resource use, and costs. An approximation to the logistic EuroSCORE
      (European System for Cardiac Operative Risk Evaluation) based on administrative
      data was used to assess surgical risk, with a computed logistic EuroSCORE > 20%
      considered high-risk. RESULTS: We identified 1474 patients with aortic stenosis
      who underwent AVR, of whom 1222 (82.9%) were non-high-risk and 252 (17.1%) were
      high-risk. Among those who were non-high-risk, the mean age was 73.3 years, 464
      (38.2%) were women, and the mean logistic EuroSCORE was 7%, whereas in those who
      were high-risk, the mean age was 77.6 years, 134 (52.8%) were women, and the mean
      logistic EuroSCORE was 37%. All-cause mortality was 33.2% for non-high-risk and
      66.7% for high-risk patients at 5 years. Over this time period, non-high-risk
      patients experienced an average of 3.9 inpatient hospitalizations and total costs
      of $106,277 per patient versus 4.7 hospitalizations and total costs of $144,183
      for high-risk patients. CONCLUSION: Among elderly patients undergoing AVR, long
      term mortality and costs are substantially greater for high-risk than for non
      high-risk individuals. These findings indicate that further research is needed to
      understand whether newer approaches to aortic valve replacement such as
      transcatheter AVR may be a lower cost, clinically valuable alternative.

PMID- 23152717
TI  - Capturing daily assessments and home treatment of congenital hemophilia with
      inhibitors: design, disposition, and implications of the Dosing Observational
      Study in Hemophilia (DOSE).
AB  - OBJECTIVE: The daily recordings of treatment by patients with congenital
      hemophilia with inhibitors and their caregivers were assessed as part of the
      Dosing Observational Study in Hemophilia (DOSE) to understand the patterns of
      bypassing agent use and health-related quality of life. METHODS: Frequently
      bleeding patients prescribed recombinant activated factor VII as first-line
      therapy were eligible. Participants recorded daily paper diaries for at least 90
      days and until at least four bleeding episodes had occurred. Web-based entry was
      optional. Assessment included bleeding status, work or school day status,
      bleeding episode, treatment, impact on planned activities, and health-related
      quality of life. RESULTS: Diaries were completed by 18 adults and 19 caregivers
      (21 children). A total of 4063 diary days and 194 bleeding episodes over 491
      bleed days were recorded. A small proportion of diary days were bleed days (8.2%)
      or treatment days (8.2%). Half the bleed days were not planned work or school
      days for patients (53%) or caregivers (48%). An exact agreement was observed
      between electronic and paper records for 93% of the reviewed health-related
      quality of life measurements. CONCLUSION: Daily diary completion by patients and
      caregivers is feasible and provides insight into the impact of congenital
      hemophilia with inhibitors on daily activities and overall quality of life.
      Positive participation and completion rates were supported by frequent patient
      contact made by independent patient support liaison personnel.

PMID- 23152718
TI  - Applying Ecodevelopmental Theory and the Theory of Reasoned Action to Understand
      HIV Risk Behaviors Among Hispanic Adolescents.
AB  - HIV/AIDS is listed as one of the top 10 reasons for the death of Hispanics
      between the ages of 15 and 54 in the United States. This cross sectional,
      descriptive secondary study proposed that using both the systemic
      (ecodevelopmental) and the individually focused (theory of reasoned action)
      theories together would lead to an increased understanding of the risk and
      protective factors that influence HIV risk behaviors in this population. The
      sample consisted of 493 Hispanic adolescent 7th and 8th graders and their
      immigrant parents living in Miami, Florida. Structural Equation Modeling (SEM)
      was used for the data analysis. Family functioning emerged as the heart of the
      model, embedded within a web of direct and mediated relationships. The data
      support the idea that family can play a central role in the prevention of
      Hispanic adolescents' risk behaviors.

PMID- 23152719
TI  - Representing the public in public engagement: the case of the 2008 UK Stem Cell
      Dialogue.

PMID- 23152721
TI  - Natural selection, not mutation: recombination in Drosophila increases diversity.

PMID- 23152720
TI  - Recombination modulates how selection affects linked sites in Drosophila.
AB  - One of the most influential observations in molecular evolution has been a strong
      association between local recombination rate and nucleotide polymorphisms across
      the genome. This is interpreted as evidence for ubiquitous natural selection. The
      alternative explanation, that recombination is mutagenic, has been rejected by
      the absence of a similar association between local recombination rate and
      nucleotide divergence between species. However, many recent studies show that
      recombination rates are often very different even in closely related species,
      questioning whether an association between recombination rate and divergence
      between species has been tested satisfactorily. To circumvent this problem, we
      directly surveyed recombination across approximately 43% of the D. pseudoobscura
      physical genome in two separate recombination maps and 31% of the D. miranda
      physical genome, and we identified both global and local differences in
      recombination rate between these two closely related species. Using only regions
      with conserved recombination rates between and within species and accounting for
      multiple covariates, our data support the conclusion that recombination is
      positively related to diversity because recombination modulates Hill-Robertson
      effects in the genome and not because recombination is predominately mutagenic.
      Finally, we find evidence for dips in diversity around nonsynonymous
      substitutions. We infer that at least some of this reduction in diversity
      resulted from selective sweeps and examine these dips in the context of
      recombination rate.

PMID- 23152722
TI  - Liver dysfunction and phosphatidylinositol-3-kinase signalling in early sepsis:
      experimental studies in rodent models of peritonitis.
AB  - BACKGROUND: Hepatic dysfunction and jaundice are traditionally viewed as late
      features of sepsis and portend poor outcomes. We hypothesized that changes in
      liver function occur early in the onset of sepsis, yet pass undetected by
      standard laboratory tests. METHODS AND FINDINGS: In a long-term rat model of
      faecal peritonitis, biotransformation and hepatobiliary transport were impaired,
      depending on subsequent disease severity, as early as 6 h after peritoneal
      contamination. Phosphatidylinositol-3-kinase (PI3K) signalling was simultaneously
      induced at this time point. At 15 h there was hepatocellular accumulation of
      bilirubin, bile acids, and xenobiotics, with disturbed bile acid conjugation and
      drug metabolism. Cholestasis was preceded by disruption of the bile acid and
      organic anion transport machinery at the canalicular pole. Inhibitors of PI3K
      partially prevented cytokine-induced loss of villi in cultured HepG2 cells.
      Notably, mice lacking the PI3Kgamma gene were protected against cholestasis and
      impaired bile acid conjugation. This was partially confirmed by an increase in
      plasma bile acids (e.g., chenodeoxycholic acid [CDCA] and taurodeoxycholic acid
      [TDCA]) observed in 48 patients on the day severe sepsis was diagnosed; unlike
      bilirubin (area under the receiver-operating curve: 0.59), these bile acids
      predicted 28-d mortality with high sensitivity and specificity (area under the
      receiver-operating curve: CDCA: 0.77; TDCA: 0.72; CDCA+TDCA: 0.87). CONCLUSIONS:
      Liver dysfunction is an early and commonplace event in the rat model of sepsis
      studied here; PI3K signalling seems to play a crucial role. All aspects of
      hepatic biotransformation are affected, with severity relating to subsequent
      prognosis. Detected changes significantly precede conventional markers and are
      reflected by early alterations in plasma bile acids. These observations carry
      important implications for the diagnosis of liver dysfunction and pharmacotherapy
      in the critically ill. Further clinical work is necessary to extend these
      concepts into clinical practice. Please see later in the article for the Editors'
      Summary.

PMID- 23152724
TI  - New signal functions to measure the ability of health facilities to provide
      routine and emergency newborn care.
AB  - Based upon an expert survey and consensus method, Sabine Gabrysch and colleagues
      recommend new signal functions to monitor and track facilities' provision of
      routine and emergency newborn care.

PMID- 23152723
TI  - G6PD deficiency prevalence and estimates of affected populations in malaria
      endemic countries: a geostatistical model-based map.
AB  - BACKGROUND: Primaquine is a key drug for malaria elimination. In addition to
      being the only drug active against the dormant relapsing forms of Plasmodium
      vivax, primaquine is the sole effective treatment of infectious P. falciparum
      gametocytes, and may interrupt transmission and help contain the spread of
      artemisinin resistance. However, primaquine can trigger haemolysis in patients
      with a deficiency in glucose-6-phosphate dehydrogenase (G6PDd). Poor information
      is available about the distribution of individuals at risk of primaquine-induced
      haemolysis. We present a continuous evidence-based prevalence map of G6PDd and
      estimates of affected populations, together with a national index of relative
      haemolytic risk. METHODS AND FINDINGS: Representative community surveys of
      phenotypic G6PDd prevalence were identified for 1,734 spatially unique sites.
      These surveys formed the evidence-base for a Bayesian geostatistical model
      adapted to the gene's X-linked inheritance, which predicted a G6PDd allele
      frequency map across malaria endemic countries (MECs) and generated population
      weighted estimates of affected populations. Highest median prevalence (peaking at
      32.5%) was predicted across sub-Saharan Africa and the Arabian Peninsula.
      Although G6PDd prevalence was generally lower across central and southeast Asia,
      rarely exceeding 20%, the majority of G6PDd individuals (67.5% median estimate)
      were from Asian countries. We estimated a G6PDd allele frequency of 8.0%
      (interquartile range: 7.4-8.8) across MECs, and 5.3% (4.4-6.7) within malaria
      eliminating countries. The reliability of the map is contingent on the underlying
      data informing the model; population heterogeneity can only be represented by the
      available surveys, and important weaknesses exist in the map across data-sparse
      regions. Uncertainty metrics are used to quantify some aspects of these
      limitations in the map. Finally, we assembled a database of G6PDd variant
      occurrences to inform a national-level index of relative G6PDd haemolytic risk.
      Asian countries, where variants were most severe, had the highest relative risks
      from G6PDd. CONCLUSIONS: G6PDd is widespread and spatially heterogeneous across
      most MECs where primaquine would be valuable for malaria control and elimination.
      The maps and population estimates presented here reflect potential risk of
      primaquine-associated harm. In the absence of non-toxic alternatives to
      primaquine, these results represent additional evidence to help inform safe use
      of this valuable, yet dangerous, component of the malaria-elimination toolkit.
      Please see later in the article for the Editors' Summary.

PMID- 23152725
TI  - New translational research provides insights into liver dysfunction in sepsis.
AB  - John Marshall discusses new research detailing the early onset in liver
      dysfunction in a rodent sepsis model, which he says can fundamentally change our
      understanding of this common clinical problem.

PMID- 23152726
TI  - The case for a smoker's license.
AB  - BACKGROUND TO THE DEBATE: Tobacco continues to kill millions of people around the
      world each year and its use is increasing in some countries, which makes the need
      for new, creative, and radical efforts to achieve the tobacco control endgame
      vitally important. One such effort is discussed in this PLOS Medicine Debate,
      where Simon Chapman presents his proposal for a "smoker's license" and Jeff
      Collin argues against. Chapman sets out a case for introducing a smart card
      license for smokers designed to limit access to tobacco products and encourage
      cessation. Key elements of the smoker's license include smokers setting daily
      limits, financial incentives for permanent license surrender, and a test of
      health risk knowledge for commencing smokers. Collin argues against the proposal,
      saying that it would shift focus away from the real vector of the epidemic--the
      tobacco industry--and that by focusing on individuals it would censure victims,
      increase stigmatization of smokers, and marginalize the poor.

PMID- 23152727
TI  - The case against a smoker's license.
AB  - BACKGROUND TO THE DEBATE: Tobacco continues to kill millions of people around the
      world each year and its use is increasing in some countries, which makes the need
      for new, creative, and radical efforts to achieve the tobacco control endgame
      vitally important. One such effort is discussed in this PLOS Medicine Debate,
      where Simon Chapman presents his proposal for a "smoker's license" and Jeff
      Collin argues against. Chapman sets out a case for introducing a smart card
      license for smokers designed to limit access to tobacco products and encourage
      cessation. Key elements of the smoker's license include smokers setting daily
      limits, financial incentives for permanent license surrender, and a test of
      health risk knowledge for commencing smokers. Collin argues against the proposal,
      saying that it would shift focus away from the real vector of the epidemic--the
      tobacco industry--and that by focusing on individuals it would censure victims,
      increase stigmatization of smokers, and marginalize the poor.

PMID- 23152728
TI  - Adrenal cortical carcinoma masquerading as pheochromocytoma: a case report.
AB  - Adrenocortical carcinoma (ACC) is a malignant tumour arising from the adrenal
      cortex, while pheochromocytoma is a catecholamine secreting tumour of the adrenal
      medulla or extra adrenal sites. Both conditions are very rare, with incidence of
      approximately 1-2 cases per million adults annually. Most adrenocortical tumours
      are functioning. ACC can be associated with clinical Cushing syndrome and
      virilisation due to excessive production of cortisol and androgens, respectively.
      However, it is rare for ACC to present clinically as pheochromocytoma. We report
      a case of a 28-year-old lady who presented with paroxysmal hypertension and
      palpitations associated with raised urinary vanillyl mandelic acid. On
      examination, there was postural hypotension and ballotable mass in right lumbar
      region with no obvious features suggestive of Cushing syndrome or virilisation. A
      huge right suprarenal mass with areas of necrosis and calcification was noted on
      the abdomen CT. A right adrenalectomy was done. The histology was consistent with
      ACC. There are reported cases of ACC presenting with clinical features of
      pheochromocytoma but limited in number, accounting for barely a dozen cases in
      the literature. This pseudopheochromocytoma may be due to the presence of
      neuroendocrine features in ACC.

PMID- 23152729
TI  - Prognostic impact of apoptosis marker Fas (CD95) and its ligand (FasL) on bladder
      cancer in Egypt: study of the effect of schistosomiasis.
AB  - OBJECTIVE: The Fas-Fas ligand (FasL) system has been recognized as a major
      pathway for the induction of apoptosis in cells and tissues. Fas-mediated
      apoptosis is deeply involved in cancer cell death brought about by the immune
      system. This study was performed to determine the Fas and FasL expression in
      human bladder cancer and the impact of schistosomiasis infection. MATERIAL AND
      METHODS: Of the 75 patients, 25 with chronic bilharzial cystitis and 50 with
      bladder cancer were included in this study. Ten control patients were included in
      the study, following their consent. Fas and FasL expressions in bladder tissue
      were determined by indirect immunohistochemistry using avidin-biotin-peroxidase
      complex (ABC) method. RESULTS: The association of bilharziasis with malignancy
      raised the incidence of Fas positive immunoreactivity to 100%. The number of
      malignant cases positive for Fas decreased with progress of tumour grade and
      stage. All control cases were negative for FasL expression. The percentage of
      positive FasL malignant cases increased with increasing tumour grade or stage.
      CONCLUSION: Malignant bladder lesions express high levels of Fas and decreased
      expression of Fas is associated with disease progression. Urinary bladder
      carcinoma acquires the functional FasL during tumour progression that may induce
      apoptosis of anti tumour T lymphocytes. Fas and FasL are recommended to be
      considered important tumour markers to define aggressive bladder cancer and may
      be included in defining the surveillance protocol for superficial bladder cancer.

PMID- 23152730
TI  - What is irritable bowel syndrome?

PMID- 23152731
TI  - Irritable bowel syndrome: how useful is the term and the 'diagnosis'?

PMID- 23152732
TI  - Irritable bowel syndrome: a multidimensional disorder cannot be understood or
      treated from a unidimensional perspective.

PMID- 23152733
TI  - Safety and efficacy of fidaxomicin in the treatment of Clostridium difficile
      associated diarrhea.
AB  - Clostridium difficile-associated diarrhea (CDAD) is the most common cause of
      healthcare-associated diarrhea. The current recommended treatment regimens of
      metronidazole and vancomycin have not changed in nearly 25 years. Fidaxomicin, an
      exceedingly narrow spectrum macrolide antibiotic, was recently approved for the
      treatment of CDAD. In phase III clinical trials, fidaxomicin was noninferior to
      vancomycin in achieving clinical cure of CDAD. Furthermore, fidaxomicin was
      associated with fewer recurrences of CDAD compared with vancomycin in clinical
      trials. These results, combined with the ease of administration and a good safety
      profile, make fidaxomicin an attractive treatment option for treating CDAD.

PMID- 23152734
TI  - Fecal microbiota transplantation in relapsing Clostridium difficile infection.
AB  - Clostridium difficile infection rates are Climbing in frequency and severity, and
      the spectrum of susceptible patients is expanding beyond the traditional scope of
      hospitalized patients receiving antibiotics. Fecal microbiota transplantation is
      becoming increasingly accepted as an effective and safe intervention in patients
      with recurrent disease, likely due to the restoration of a disrupted microbiome.
      Cure rates of > 90% are being consistently reported from multiple centers.
      Transplantation can be provided through a variety of methodologies, either to the
      lower proximal, lower distal, or upper gastrointestinal tract. This review
      summarizes reported results, factors in donor selection, appropriate patient
      criteria, and the various preparations and mechanisms of fecal microbiota
      transplant delivery available to clinicians and patients.

PMID- 23152736
TI  - Single-balloon enteroscopy in managing Peutz Jeghers syndrome polyps.

PMID- 23152735
TI  - Management of patients with difficult autoimmune hepatitis.
AB  - Autoimmune hepatitis (AIH) is characterized by a T-cell rich infiltrate
      associated with lobular and interface hepatitis, hypergammaglobulinemia and
      production of autoantibodies. Genetic risk is linked to the HLA particularly
      DRB1*0301 and DRB1*0401 alleles in North American and European Caucasian
      populations. It has recently been suggested that functional deficiencies in
      CD4(+)CD25(+)CD127(low)FOXP3(+) regulatory T cells contribute to the breakdown of
      immune tolerance that results in AIH. Most patients respond to immunosuppressive
      therapy with corticosteroids and can be maintained in remission by low-dose
      corticosteroid treatment and/or azathioprine. For those who progress to end-stage
      disease liver transplantation is an effective treatment although it is associated
      with recurrence. In the future it is likely that biological therapies will allow
      more targeted therapy designed to switch the balance to immune regulation and
      thereby restore immune homeostasis. Although treatment for many cases is
      relatively straightforward and successful problems are encountered in those who
      fail to respond to standard treatment, are unable to tolerate it or relapse. In
      such cases alternative therapies should be considered. In addition treatment is
      complicated in some patients by comorbidity and special care is required during
      and after pregnancy. We will discuss the current and future therapeutic options
      for patients with difficult to treat AIH.

PMID- 23152738
TI  - Continuous control.

PMID- 23152737
TI  - The deactivation of implantable cardioverter-defibrillators: medical, ethical,
      practical, and legal considerations.
AB  - BACKGROUND: Implantable cardioverter-defibrillators (ICDs) cannot prevent death
      from progressive heart failure or non-cardiac disease. Patients with ICDs may
      receive defibrillation therapy from their devices in the last days of their
      lives, when such therapy does not accord with the goal of palliative treatment,
      but rather lowers these patients' quality of life and compromises their dignity.
      METHODS: We present a case report and a selective review of pertinent literature
      retrieved by a PubMed search, including two up-to-date consensus documents.
      RESULTS: One-third to two-thirds of all ICD patients receive defibrillation
      therapy in the final days of their lives. Patients and their physicians rarely
      discuss deactivating the ICD. The ethical aspects of such decisions need to be
      considered. As a practical matter, it is possible to deactivate certain types of
      electrotherapy selectively, while leaving others active. There are logistical
      considerations as well. CONCLUSION: Automatic defibrillation therapy in a
      terminally ill patient with an ICD is painful and distressing, serves no medical
      purpose, and should be avoided. This issue should be discussed with ICD patients
      and their families. Institutions caring for terminally ill patients, as well as
      cardiology units where ICD patients are treated, should develop ethically and
      legally well-founded protocols for dealing with the question of ICD deactivation.

PMID- 23152739
TI  - Neither procedure is superior.

PMID- 23152740
TI  - Highly effective.

PMID- 23152741
TI  - Psychosomatic component.

PMID- 23152742
TI  - Drug interactions--principles, examples and clinical consequences.
AB  - BACKGROUND: Drug interactions can have desired, reduced or unwanted effects. The
      probability of interactions increases with the number of drugs taken. The high
      rate of prescribed drugs in elderly patients (65-year-old patients take an
      average of 5 drugs) increases the likelihood of drug interactions and thus the
      risk that drugs themselves can be the cause of hospitalization. According to meta
      analyses, up to 7% of hospitalizations are drug-related. METHODS: Selective
      literature review. RESULTS: Drug interactions occur on pharmacodynamic and
      pharmacokinetic levels. Examples of pharmacodynamic interactions are simultaneous
      administration of a NSAID and phenprocoumon (additive interaction), or of aspirin
      and ibuprofen (antagonistic interaction). Pharmacokinetic interactions occur at
      the levels of absorption (e.g., levothyroxine and neutralizing antacids),
      elimination (e.g., digoxin and macrolides), and metabolism, as in the competition
      for cytochrome P450 enzymes (e.g., SSRIs and certain beta-blockers). CONCLUSION:
      The systematic knowledge of drug interaction, in particular on the level of
      absorption, elimination, transport and drug metabolism may help to prevent
      adverse effects. Predicting pharmacodynamic interactions often demands a deeper
      understanding of the mechanisms of effect. Electronic prescribing systems are
      helpful.

PMID- 23152743
TI  - Comprehensive miRNA expression analysis in peripheral blood can diagnose liver
      disease.
AB  - BACKGROUND: miRNAs circulating in the blood in a cell-free form have been
      acknowledged for their potential as readily accessible disease markers.
      Presently, histological examination is the golden standard for diagnosing and
      grading liver disease, therefore non-invasive options are desirable. Here, we
      investigated if miRNA expression profile in exosome rich fractionated serum could
      be useful for determining the disease parameters in patients with chronic
      hepatitis C (CHC). METHODOLOGY: Exosome rich fractionated RNA was extracted from
      the serum of 64 CHC and 24 controls with normal liver (NL). Extracted RNA was
      subjected to miRNA profiling by microarray and real-time qPCR analysis. The miRNA
      expression profiles from 4 chronic hepatitis B (CHB) and 12 non alcoholic
      steatohepatitis (NASH) patients were also established. The resulting miRNA
      expression was compared to the stage or grade of CHC determined by blood
      examination and histological inspection. PRINCIPAL FINDINGS: miRNAs implicated in
      chronic liver disease and inflammation showed expression profiles that differed
      from those in NL and varied among the types and grades of liver diseases. Using
      the expression patterns of nine miRNAs, we classified CHC and NL with 96.59%
      accuracy. Additionally, we could link miRNA expression pattern with liver
      fibrosis stage and grade of liver inflammation in CHC. In particular, the miRNA
      expression pattern for early fibrotic stage differed greatly from that observed
      in high inflammation grades. CONCLUSIONS: We demonstrated that miRNA expression
      pattern in exosome rich fractionated serum shows a high potential as a biomarker
      for diagnosing the grade and stage of liver diseases.

PMID- 23152744
TI  - NetView: a high-definition network-visualization approach to detect fine-scale
      population structures from genome-wide patterns of variation.
AB  - High-throughput sequencing and single nucleotide polymorphism (SNP) genotyping
      can be used to infer complex population structures. Fine-scale population
      structure analysis tracing individual ancestry remains one of the major
      challenges. Based on network theory and recent advances in SNP chip technology,
      we investigated an unsupervised network clustering method called Super
      Paramagnetic Clustering (Spc). When applied to whole-genome marker data it
      identifies the natural divisions of groups of individuals into population
      clusters without use of prior ancestry information. Furthermore, we optimised an
      analysis pipeline called NetView, a high-definition network visualization,
      starting with computation of genetic distance, followed clustering using Spc and
      finally visualization of clusters with Cytoscape. We compared NetView against
      commonly used methodologies including Principal Component Analyses (PCA) and a
      model-based algorithm, Admixture, on whole-genome-wide SNP data derived from
      three previously described data sets: simulated (2.5 million SNPs, 5
      populations), human (1.4 million SNPs, 11 populations) and cattle (32,653 SNPs,
      19 populations). We demonstrate that individuals can be effectively allocated to
      their correct population whilst simultaneously revealing fine-scale structure
      within the populations. Analyzing the human HapMap populations, we identified
      unexpected genetic relatedness among individuals, and population stratification
      within the Indian, African and Mexican samples. In the cattle data set, we
      correctly assigned all individuals to their respective breeds and detected fine
      scale population sub-structures reflecting different sample origins and
      phenotypes. The NetView pipeline is computationally extremely efficient and can
      be easily applied on large-scale genome-wide data sets to assign individuals to
      particular populations and to reproduce fine-scale population structures without
      prior knowledge of individual ancestry. NetView can be used on any data from
      which a genetic relationship/distance between individuals can be calculated.

PMID- 23152745
TI  - Incidence, clinical spectrum, risk factors and impact of HIV-associated immune
      reconstitution inflammatory syndrome in South Africa.
AB  - BACKGROUND: Immune reconstitution inflammatory syndrome (IRIS) is a widely
      recognised complication of antiretroviral therapy (ART), but there are still
      limited data from resource-limited settings. Our objective was to characterize
      the incidence, clinical spectrum, risk factors and contribution to mortality of
      IRIS in two urban ART clinics in South Africa. METHODS AND FINDINGS: 498 adults
      initiating ART in Durban, South Africa were followed prospectively for 24 weeks.
      IRIS diagnosis was based on consensus expert opinion, and classified by mode of
      presentation (paradoxical worsening of known opportunistic infection [OI] or
      unmasking of subclinical disease). 114 patients (22.9%) developed IRIS (36%
      paradoxical, 64% unmasking). Mucocutaneous conditions accounted for 68% of IRIS
      events, mainly folliculitis, warts, genital ulcers and herpes zoster.
      Tuberculosis (TB) accounted for 25% of IRIS events. 18/135 (13.3%) patients with
      major pre-ART OIs (e.g. TB, cryptococcosis) developed paradoxical IRIS related to
      the same OI. Risk factors for this type of IRIS were baseline viral load >5.5 vs.
      <4.5 log(10) (adjusted hazard ratio 7.23; 95% confidence interval 1.35-38.76) and
      <=30 vs. >30 days of OI treatment prior to ART (2.66; 1.16-6.09). Unmasking IRIS
      related to major OIs occurred in 25/498 patients (5.0%), and risk factors for
      this type of IRIS were baseline C-reactive protein >=25 vs. <25 mg/L (2.77; 1.31
      5.85), haemoglobin <10 vs. >12 g/dL (3.36; 1.32-8.52), >=10% vs. <10% weight loss
      prior to ART (2.31; 1.05-5.11) and mediastinal lymphadenopathy on pre-ART chest x
      ray (9.15; 4.10-20.42). IRIS accounted for 6/25 (24%) deaths, 13/65 (20%)
      hospitalizations and 10/35 (29%) ART interruptions or discontinuations.
      CONCLUSION: IRIS occurred in almost one quarter of patients initiating ART, and
      accounted for one quarter of deaths in the first 6 months. Priority strategies to
      reduce IRIS-associated morbidity and mortality in ART programmes include earlier
      ART initiation before onset of advanced immunodeficiency, improved pre-ART
      screening for TB and cryptococcal infection, optimization of OI therapy prior to
      ART initiation, more intensive clinical monitoring in initial weeks of ART, and
      education of health care workers and patients about IRIS.

PMID- 23152746
TI  - An efficient kinetic model for assemblies of amyloid fibrils and its application
      to polyglutamine aggregation.
AB  - Protein polymerization consists in the aggregation of single monomers into
      polymers that may fragment. Fibrils assembly is a key process in amyloid
      diseases. Up to now, protein aggregation was commonly mathematically simulated by
      a polymer size-structured ordinary differential equations (ODE) system, which is
      infinite by definition and therefore leads to high computational costs. Moreover,
      this Ordinary Differential Equation-based modeling approach implies biological
      assumptions that may be difficult to justify in the general case. For example,
      whereas several ordinary differential equation models use the assumption that
      polymerization would occur at a constant rate independently of polymer size, it
      cannot be applied to certain protein aggregation mechanisms. Here, we propose a
      novel and efficient analytical method, capable of modelling and simulating
      amyloid aggregation processes. This alternative approach consists of an integro
      Partial Differential Equation (PDE) model of coalescence-fragmentation type that
      was mathematically derived from the infinite differential system by asymptotic
      analysis. To illustrate the efficiency of our approach, we applied it to
      aggregation experiments on polyglutamine polymers that are involved in
      Huntington's disease. Our model demonstrates the existence of a monomeric
      structural intermediate [Formula: see text] acting as a nucleus and deriving from
      a non polymerizing monomer ([Formula: see text]). Furthermore, we compared our
      model to previously published works carried out in different contexts and proved
      its accuracy to describe other amyloid aggregation processes.

PMID- 23152747
TI  - The molecular clockwork of the fire ant Solenopsis invicta.
AB  - The circadian clock is a core molecular mechanism that allows organisms to
      anticipate daily environmental changes and adapt the timing of behaviors to
      maximize efficiency. In social insects, the ability to maintain the appropriate
      temporal order is thought to improve colony efficiency and fitness. We used the
      newly sequenced fire ant (Solenopsis invicta) genome to characterize the first
      ant circadian clock. Our results reveal that the fire ant clock is similar to the
      clock of the honeybee, a social insect with an independent evolutionary origin of
      sociality. Gene trees for the eight core clock genes, period, cycle, clock,
      cryptochrome-m, timeout, vrille, par domain protein 1 & clockwork orange, show
      ant species grouping closely with honeybees and Nasonia wasps as an outgroup to
      the social Hymenoptera. Expression patterns for these genes suggest that the ant
      clock functions similar to the honeybee clock, with period and cry-m mRNA levels
      increasing during the night and cycle and clockwork orange mRNAs cycling
      approximately anti-phase to period. Gene models for five of these genes also
      parallel honeybee models. In particular, the single ant cryptochrome is an
      ortholog of the mammalian-type (cry-m), rather than Drosophila-like protein (cry
      d). Additionally, we find a conserved VPIFAL C-tail region in clockwork orange
      shared by insects but absent in vertebrates. Overall, our characterization of the
      ant clock demonstrates that two social insect lineages, ants and bees, share a
      similar, mammalian-like circadian clock. This study represents the first
      characterization of clock genes in an ant and is a key step towards understanding
      socially-regulated plasticity in circadian rhythms by facilitating comparative
      studies on the organization of circadian clockwork.

PMID- 23152748
TI  - Demographic consequences of predators on prey: trait and density mediated effects
      on mosquito larvae in containers.
AB  - Predators may affect prey population growth and community diversity through
      density mediated lethal and trait mediated non-lethal effects that influence
      phenotypic traits of prey. We tested experimentally the roles of thinning the
      density of prey (lethality) in the absence of predator cues and density and trait
      mediated effects (lethality + intimidation) of predatory midge Corethrella
      appendiculata on competing native and invasive mosquito prey. Predator-mediated
      reductions in prey and density reductions in the absence of C. appendiculata
      resulted in lower percent survivorship to adulthood and estimates of the finite
      rate of increase (lambda') for invasive mosquito Aedes albopictus relative to
      that of controls. In most instances, thinning the density of prey in the absence,
      but not in the presence, of C. appendiculata cues resulted in lower survivorship
      to adulthood and lambda' for native mosquito Aedes triseriatus relative to that
      of controls. Together, these results suggested trait mediated effects of C.
      appendiculata specific to each species of mosquito prey. Release from
      intraspecific competition attributable to density reductions in the absence, but
      not in the presence, of C. appendiculata enhanced growth and lengthened adult
      lifespan relative to that of controls for A. albopictus but not A. triseriatus.
      These results show the importance of predator-mediated density and trait mediated
      effects on phenotypic traits and populations of invasive and native mosquitoes.
      Species-specific differences in the phenotypic responses of prey may be due, in
      part, to longer evolutionary history of C. appendiculata with A. triseriatus than
      A. albopictus.

PMID- 23152749
TI  - Ecological factors driving avian influenza virus dynamics in Spanish wetland
      ecosystems.
AB  - Studies exploring the ecological interactions between avian influenza viruses
      (AIV), natural hosts and the environment are scarce. Most work has focused on
      viral survival and transmission under laboratory conditions and through
      mathematical modelling. However, more integrated studies performed under field
      conditions are required to validate these results. In this study, we combined
      information on bird community, environmental factors and viral epidemiology to
      assess the contribution of biotic and abiotic factors in the occurrence of low
      pathogenic AIV in Spanish wetlands. For that purpose, seven locations in five
      different wetlands were studied during two years (2007-2009), including seven
      sampling visits by location. In each survey, fresh faeces (n = 4578) of wild
      birds and water samples were collected for viral detection. Also, the vegetation
      structure, water physical properties of wetlands, climatic conditions and wild
      bird community composition were determined. An overall AIV prevalence of 1.7%+/
      0.4 was detected in faecal samples with important fluctuations among seasons and
      locations. Twenty-six AIV were isolated from the 78 RRT-PCR positive samples and
      eight different haemagglutinines and five neuraminidases were identified, being
      the combination H3N8 the most frequent. Variation partitioning procedures
      identified the combination of space and time variables as the most important pure
      factor - independently to other factors - explaining the variation in AIV
      prevalence (36.8%), followed by meteorological factor (21.5%) and wild bird
      community composition/vegetation structure (21.1%). These results contribute to
      the understanding of AIV ecological drivers in Spanish ecosystems and provide
      useful guidelines for AIV risk assessment identifying potential hotspots of AIV
      activity.

PMID- 23152750
TI  - A working memory deficit among dyslexic readers with no phonological impairment
      as measured using the n-back task: an fNIR study.
AB  - Data indicated that dyslexic individuals exhibited difficulties on tasks
      involving Working Memory (WM). Previous studies have suggested that these
      deficits stem from impaired processing in the Phonological Loop (PL). The PL
      impairment was connected to poor phonological processing. However, recent data
      has pointed to the Central Executive (CE) system as another source of WM deficit
      in dyslexic readers. This opened a debate whether the WM deficit stems solely
      from PL or can also be seen as an outcome of poor CE processing. In an attempt to
      verify this question, the current study compared adult skilled and compensated
      dyslexic readers with no impairment of phonological skills. The participants' PL
      and CE processing were tested by using the fNIR device attached to the frontal
      lobe and measured the changes in brain oxygen values when performing N-back task.
      As it was previously suggested, the N = 0 represented PL and N = 1 to 3 represent
      CE processing. It was hypothesized that dyslexic readers who show non-impaired
      phonological skills will exhibit deficits mainly in the CE subsystem and to a
      lesser extent in the PL. Results indicated that the two reading level groups did
      not differ in their accuracy and reaction times in any of the N-Back conditions.
      However, the dyslexic readers demonstrated significant lower maximum oxyHb values
      in the upper left frontal lobe, mainly caused due to a significant lower activity
      under the N = 1 condition. Significant task effects were found in the medial left
      hemisphere, and the high medial right hemisphere. In addition, significant
      correlations between fNIR-features, reading performance and speed of processing
      were found. The higher oxyHb values, the better reading and speed of processing
      performance obtained. The results of the current study support the hypothesis
      that at least for the group of dyslexics with non-impaired PL, WM deficit stems
      from poor CE activity.

PMID- 23152751
TI  - Accelerating the Gillespie Exact Stochastic Simulation Algorithm using hybrid
      parallel execution on graphics processing units.
AB  - The Gillespie Stochastic Simulation Algorithm (GSSA) and its variants are
      cornerstone techniques to simulate reaction kinetics in situations where the
      concentration of the reactant is too low to allow deterministic techniques such
      as differential equations. The inherent limitations of the GSSA include the time
      required for executing a single run and the need for multiple runs for parameter
      sweep exercises due to the stochastic nature of the simulation. Even very
      efficient variants of GSSA are prohibitively expensive to compute and perform
      parameter sweeps. Here we present a novel variant of the exact GSSA that is
      amenable to acceleration by using graphics processing units (GPUs). We
      parallelize the execution of a single realization across threads in a warp (fine
      grained parallelism). A warp is a collection of threads that are executed
      synchronously on a single multi-processor. Warps executing in parallel on
      different multi-processors (coarse-grained parallelism) simultaneously generate
      multiple trajectories. Novel data-structures and algorithms reduce memory
      traffic, which is the bottleneck in computing the GSSA. Our benchmarks show an 8*
      120* performance gain over various state-of-the-art serial algorithms when
      simulating different types of models.

PMID- 23152752
TI  - Human exposure pathways of heavy metals in a lead-zinc mining area, Jiangsu
      Province, China.
AB  - Heavy metal pollution is becoming a serious issue in developing countries such as
      China, and the public is increasingly aware of its adverse health impacts in
      recent years. We assessed the potential health risks in a lead-zinc mining area
      and attempted to identify the key exposure pathways. We evaluated the spatial
      distributions of personal exposure using indigenous exposure factors and field
      monitoring results of water, soil, food, and indoor and outdoor air samples. The
      risks posed by 10 metals and the contribution of inhalation, ingestion and dermal
      contact pathways to these risks were estimated. Human hair samples were also
      analyzed to indicate the exposure level in the human body. Our results show that
      heavy metal pollution may pose high potential health risks to local residents,
      especially in the village closest to the mine (V1), mainly due to Pb, Cd and Hg.
      Correspondingly, the residents in V1 had higher Pb (8.14 mg/kg) levels in hair
      than those in the other two villages. Most of the estimated risks came from soil,
      the intake of self-produced vegetables and indoor air inhalation. This study
      highlights the importance of site-specific multipathway health risk assessments
      in studying heavy-metal exposures in China.

PMID- 23152753
TI  - Dynamic 3D scene depth reconstruction via optical flow field rectification.
AB  - In this paper, we propose a depth propagation scheme based on optical flow field
      rectification towards more accurate depth reconstruction. In depth
      reconstruction, the occlusions and low-textural regions easily result in optical
      flow field errors, which lead ambiguous depth value or holes without depth in the
      obtained depth map. In this work, a scheme is proposed to improve the precision
      of depth propagation and the quality of depth reconstruction for dynamic scene.
      The proposed scheme first adaptively detects the occlusive or low-textural
      regions, and the obtained vectors in optical flow field are rectified properly.
      Subsequently, we process the occluded and ambiguous vectors for more precise
      depth propagation. We further leverage the boundary enhancement filters as a post
      processing to sharpen the object boundaries in obtained depth maps for better
      quality. Quantitative evaluations show that the proposed scheme can reconstruct
      depth map with higher accuracy and better quality compared with the state-of-the
      art methods.

PMID- 23152754
TI  - The biological variation of N-terminal pro-brain natriuretic peptide in
      postmenopausal women with type 2 diabetes: a case control study.
AB  - BACKGROUND: The incidence of heart failure in type 2 diabetes is high and it has
      poorer prognosis when compared with patients without diabetes. Access to
      echocardiography is limited and alternative methods to identify early heart
      failure such as the measurement of natriuretic peptides levels have been
      proposed. However, their wide biological variation could limit their clinical
      utility. Our aim was to determine if the intrinsic biological variation of one of
      these peptides, N-terminal proBNP, is as wide in type 2 diabetes as it is in
      health and to calculate the critical difference values that could be utilised in
      clinical practice to ensure changes observed between two samples are due to
      intervention rather than to its biological variability. METHODOLOGY/PRINCIPAL
      FINDINGS: 12 postmenopausal women with diet controlled type 2 diabetes and
      without heart failure were compared with 11 control postmenopausal women without
      diabetes. N-terminal proBNP levels were measured on 10 occasions. The biological
      variation was calculated according to Fraser's methods. The mean NT-proBNP level
      was similar in both groups (mean +/- standard deviation; type 2 diabetes, 10.7
      pmol/L+/- 8.5 versus 8.49+/-6.0 pmol/L, p = 0.42). The biological variation was
      also similarly wide. The critical difference in patients with type 2 diabetes was
      between -70% and +/-236%. CONCLUSIONS: Type 2 diabetes does not appear to
      significantly influence the marked biological variation of N-terminal proBNP in
      postmenopausal women. The critical difference values reported in this study could
      be used to titrate therapy or monitor response to interventions although the
      change required in between samples is wide and this might limit its utility.

PMID- 23152756
TI  - The diamine oxidase gene is associated with hypersensitivity response to non
      steroidal anti-inflammatory drugs.
AB  - Non-steroidal anti-inflammatory drugs (NSAIDs) are the drugs most frequently
      involved in hypersensitivity drug reactions. Histamine is released in the
      allergic response to NSAIDs and is responsible for some of the clinical symptoms.
      The aim of this study is to analyze clinical association of functional
      polymorphisms in the genes coding for enzymes involved in histamine homeostasis
      with hypersensitivity response to NSAIDs. We studied a cohort of 442 unrelated
      Caucasian patients with hypersensitivity to NSAIDs. Patients who experienced
      three or more episodes with two or more different NSAIDs were included. If this
      requirement was not met diagnosis was established by challenge. A total of 414
      healthy unrelated controls ethnically matched with patients and from the same
      geographic area were recruited. Analyses of the SNPs rs17740607, rs2073440,
      rs1801105, rs2052129, rs10156191, rs1049742 and rs1049793 in the HDC, HNMT and
      DAO genes were carried out by means of TaqMan assays. The detrimental DAO 16 Met
      allele (rs10156191), which causes decreased metabolic capacity, is
      overrepresented among patients with crossed-hypersensitivity to NSAIDs with an OR
      = 1.7 (95% CI  = 1.3-2.1; Pc  = 0.0003) with a gene-dose effect (P = 0.0001).
      The association was replicated in two populations from different geographic areas
      (Pc  = 0.008 and Pc  = 0.004, respectively). CONCLUSIONS AND IMPLICATIONS: The
      DAO polymorphism rs10156191 which causes impaired metabolism of circulating
      histamine is associated with the clinical response in crossed-hypersensitivity to
      NSAIDs and could be used as a biomarker of response.

PMID- 23152755
TI  - Reconstruction of the evolutionary dynamics of the A(H1N1)pdm09 influenza virus
      in Italy during the pandemic and post-pandemic phases.
AB  - The aim of this study was to reconstruct the evolutionary dynamics of the
      A(H1N1)pdm09 influenza virus in Italy during two epidemic seasons (2009/2010 and
      2010/2011) in the light of the forces driving the evolution of the virus. Nearly
      six thousands respiratory specimens were collected from patients with influenza
      like illness within the framework of the Italian Influenza Surveillance Network,
      and the A(H1N1)pdm09 hemagglutinin (HA) gene was amplified and directly sequenced
      from 227 of these. Phylodynamic and phylogeographical analyses were made using a
      Bayesian Markov Chain Monte Carlo method, and codon-specific positive selection
      acting on the HA coding sequence was evaluated. The global and local phylogenetic
      analyses showed that all of the Italian sequences sampled in the post-pandemic
      (2010/2011) season grouped into at least four highly significant Italian clades,
      whereas those of the pandemic season (2009/2010) were interspersed with isolates
      from other countries at the tree root. The time of the most recent common
      ancestor of the strains circulating in the pandemic season in Italy was estimated
      to be between the spring and summer of 2009, whereas the Italian clades of the
      post-pandemic season originated in the spring of 2010 and showed radiation in the
      summer/autumn of the same year; this was confirmed by a Bayesian skyline plot
      showing the biphasic growth of the effective number of infections. The local
      phylogeography analysis showed that the first season of infection originated in
      Northern Italian localities with high density populations, whereas the second
      involved less densely populated localities, in line with a gravity-like model of
      geographical dispersion. Two HA sites, codons 97 and 222, were under positive
      selection. In conclusion, the A(H1N1)pdm09 virus was introduced into Italy in the
      spring of 2009 by means of multiple importations. This was followed by repeated
      founder effects in the post-pandemic period that originated specific Italian
      clades.

PMID- 23152757
TI  - Automatic classification of early Parkinson's disease with multi-modal MR
      imaging.
AB  - BACKGROUND: In recent years, neuroimaging has been increasingly used as an
      objective method for the diagnosis of Parkinson's disease (PD). Most previous
      studies were based on invasive imaging modalities or on a single modality which
      was not an ideal diagnostic tool. In this study, we developed a non-invasive
      technology intended for use in the diagnosis of early PD by integrating the
      advantages of various modals. MATERIALS AND METHODS: Nineteen early PD patients
      and twenty-seven normal volunteers participated in this study. For each subject,
      we collected resting-state functional magnetic resonance imaging (rsfMRI) and
      structural images. For the rsfMRI images, we extracted the characteristics at
      three different levels: ALFF (amplitude of low-frequency fluctuations), ReHo
      (regional homogeneity) and RFCS (regional functional connectivity strength). For
      the structural images, we extracted the volume characteristics from the gray
      matter (GM), the white matter (WM) and the cerebrospinal fluid (CSF). A two
      sample t-test was used for the feature selection, and then the remaining features
      were fused for classification. Finally a classifier for early PD patients and
      normal control subjects was identified from support vector machine training. The
      performance of the classifier was evaluated using the leave-one-out cross
      validation method. RESULTS: Using the proposed methods to classify the data set,
      good results (accuracy  = 86.96%, sensitivity  = 78.95%, specificity  = 92.59%)
      were obtained. CONCLUSIONS: This method demonstrates a promising diagnosis
      performance by the integration of information from a variety of imaging
      modalities, and it shows potential for improving the clinical diagnosis and
      treatment of PD.

PMID- 23152758
TI  - The semaphorin 3A inhibitor SM-345431 accelerates peripheral nerve regeneration
      and sensitivity in a murine corneal transplantation model.
AB  - BACKGROUND: Peripheral nerve damage of the cornea is a complication following
      surgery or infection which may lead to decreased visual function. We examined the
      efficacy of the semaphorin 3A inhibitor, SM-345431, in promoting regeneration of
      peripheral nerves in a mouse corneal transplantation model. METHODOLOGY/PRINCIPAL
      FINDINGS: P0-Cre/Floxed-EGFP mice which express EGFP in peripheral nerves cells
      were used as recipients of corneal transplantation with syngeneic wild-type mouse
      cornea donors. SM-345431 was administered subconjunctivally every 2 days while
      control mice received vehicle only. Mice were followed for 3 weeks and the length
      of regenerating nerves was measured by EGFP fluorescence and immunohistochemistry
      against betaIII tubulin. Cornea sensitivity was also measured by the Cochet
      Bonnet esthesiometer. CD31 staining was used to determine corneal
      neovascularization as a possible side effect of SM-345431. Regeneration of
      betaIII tubulin positive peripheral nerves was significantly higher in SM-345431
      treated mice compared to control. Furthermore, corneal sensitivity significantly
      improved in the SM-345431 group by 3 weeks after transplantation.
      Neovascularization was limited to the peripheral cornea with no difference
      between SM-345431 group and control. CONCLUSIONS/SIGNIFICANCE: Subconjunctival
      injections of SM-345431 promoted a robust network of regenerating nerves as well
      as functional recovery of corneal sensation in a mouse keratoplasty model,
      suggesting a novel therapeutic strategy for treating neurotrophic corneal
      disease.

PMID- 23152759
TI  - Analysis of the clonality of Candida tropicalis strains from a general hospital
      in Beijing using multilocus sequence typing.
AB  - Multilocus sequence typing (MLST) based on six loci was used to analyze the
      relationship of 58 Candida tropicalis isolates from individual patients in a
      general hospital in Beijing, China. A total of 52 diploid sequence types (DSTs)
      were generated by the MLST, all of which were new to the central database.
      Unweighted Pair Group Method with Arithmetic Mean (UPGMA) dendrograms were
      constructed, which showed that the 58 isolates were distributed robustly and 6
      main groups were clustered regardless of the specimen source and medical
      department. The minimum spanning tree (MST) of the 58 isolates (52 DSTs) and all
      401 isolates (268 DSTs) in the C. tropicalis central database
      (http://pubmlst.org/ctropicalis/) indicated that the isolates in this study
      clustered in three relative pure clonal complexes, and 2 clustered with isolates
      from Taiwan, Belgium, Brazil, and the US. This study presents the first MLST
      analysis of C. tropicalis isolates from Mainland China, which may be useful for
      further studies on the similarity, genetic relationship, and molecular
      epidemiology of C. tropicalis strains worldwide.

PMID- 23152761
TI  - A simple state-determined model reproduces entrainment and phase-locking of human
      walking.
AB  - Theoretical studies and robotic experiments have shown that asymptotically stable
      periodic walking may emerge from nonlinear limit-cycle oscillators in the neuro
      mechanical periphery. We recently reported entrainment of human gait to periodic
      mechanical perturbations with two essential features: 1) entrainment occurred
      only when the perturbation period was close to the original (preferred) walking
      period, and 2) entrainment was always accompanied by phase locking so that the
      perturbation occurred at the end of the double-stance phase. In this study, we
      show that a highly-simplified state-determined walking model can reproduce
      several salient nonlinear limit-cycle behaviors of human walking: 1) periodic
      gait that is 2) asymptotically stable; 3) entrainment to periodic mechanical
      perturbations only when the perturbation period is close to the model's
      unperturbed period; and 4) phase-locking to locate the perturbation at the end of
      double stance. Importantly, this model requires neither supra-spinal control nor
      an intrinsic self-sustaining neural oscillator such as a rhythmic central pattern
      generator. Our results suggest that several prominent limit-cycle features of
      human walking may stem from simple afferent feedback processes without
      significant involvement of supra-spinal control or a self-sustaining oscillatory
      neural network.

PMID- 23152760
TI  - BmTGIF, a Bombyx mori homolog of Drosophila DmTGIF, regulates progression of
      spermatogenesis.
AB  - TG-interacting factor (TGIF) in Drosophila consists of two tandemly-repeated
      genes, achintya (Dmachi) and vismay (Dmvis), which act as transcriptional
      activators in Drosophila spermatogenesis. In contrast, TGIF in humans is a
      transcriptional repressor that binds directly to DNA or interacts with
      corepressors to repress the transcription of target genes. In this study, we
      investigated the characteristics and functions of BmTGIF, a Bombyx mori homolog
      of DmTGIF. Like DmTGIF, BmTGIF is predominantly expressed in the testes and
      ovaries. Four alternatively spliced isoforms could be isolated from testes, and
      two isoforms from ovaries. Quantitative polymerase chain reaction indicated
      BmTGIF was abundantly expressed in the testis of 3rd instar larvae, when the
      testis is almost full of primary spermatocytes. The results of luciferase assays
      indicated that BmTGIF contains two adjacent acidic domains that activate the
      transcription of reporter genes. Immunofluorescence assay in BmN cells showed
      that the BmTGIF protein was located mainly in the nucleus, and paraffin sections
      of testis showed BmTGIF was grossly expressed in primary spermatocytes and mature
      sperms. Consistent with the role of DmVis in Drosophila development, BmTGIF
      significantly affected spermatid differentiation, as indicated by hematoxylin
      eosin staining of paraffin sections of testis from BmTGIF-small interfering RNA
      (siRNA)-injected male silkworms. Co-immunoprecipitation experiments suggested
      that BmTGIF interacted with BmAly, and that they may recruit other factors to
      form a complex to regulate the genes required for meiotic divisions and spermatid
      differentiation. The results of this analysis of BmTGIF will improve our
      understanding of the mechanism of spermatid differentiation in B. mori, with
      potential applications for pest control.

PMID- 23152762
TI  - High uptake of HIV testing in pregnant women in Ontario, Canada.
AB  - In 1999, Ontario implemented a policy to offer HIV counseling and testing to all
      pregnant women and undertook measures to increase HIV testing. We evaluated the
      effectiveness of the new policy by examining HIV test uptake, the number of HIV
      infected women identified and, in 2002, the HIV rate in women not tested during
      prenatal care. We analyzed test uptake among women receiving prenatal care from
      1999 to 2010. We examined HIV test uptake and HIV rate by year, age and health
      region. In an anonymous, unlinked study, we determined the HIV rate in pregnant
      women not tested. Prenatal HIV test uptake in Ontario increased dramatically,
      from 33% in the first quarter of 1999 to 96% in 2010. Test uptake was highest in
      younger women but increased in all age groups. All health regions improved and
      experienced similar test uptake in recent years. The HIV rate among pregnant
      women tested in 2010 was 0.13/1,000; in Toronto, the rate was 0.28 per 1,000. In
      the 2002 unlinked study, the HIV rate was 0.62/1,000 among women not tested in
      pregnancy compared to 0.31/1,000 among tested women. HIV incidence among women
      who tested more than once was 0.05/1,000 person-years. In response to the new
      policy in Ontario, prenatal HIV testing uptake improved dramatically among women
      in all age groups and health regions. A reminder to physicians who had not
      ordered a prenatal HIV test appeared to be very effective. In 2002, the HIV rate
      in women who were not tested was twice that of tested women: though 77% of
      pregnant women had been tested, only 63% of HIV-infected women were tested. HIV
      testing uptake was estimated at 98% in 2010.

PMID- 23152764
TI  - Using wind tunnels to predict bird mortality in wind farms: the case of griffon
      vultures.
AB  - BACKGROUND: Wind farms have shown a spectacular growth during the last 15 years.
      Avian mortality through collision with moving rotor blades is well-known as one
      of the main adverse impacts of wind farms. In Spain, the griffon vulture incurs
      the highest mortality rates in wind farms. METHODOLOGY/PRINCIPAL FINDINGS: As far
      as we know, this study is the first attempt to predict flight trajectories of
      birds in order to foresee potentially dangerous areas for wind farm development.
      We analyse topography and wind flows in relation to flight paths of griffon
      vultures, using a scaled model of the wind farm area in an aerodynamic wind
      tunnel, and test the difference between the observed flight paths of griffon
      vultures and the predominant wind flows. Different wind currents for each wind
      direction in the aerodynamic model were observed. Simulations of wind flows in a
      wind tunnel were compared with observed flight paths of griffon vultures. No
      statistical differences were detected between the observed flight trajectories of
      griffon vultures and the wind passages observed in our wind tunnel model. A
      significant correlation was found between dead vultures predicted proportion of
      vultures crossing those cells according to the aerodynamic model. CONCLUSIONS:
      Griffon vulture flight routes matched the predominant wind flows in the area
      (i.e. they followed the routes where less flight effort was needed). We suggest
      using these kinds of simulations to predict flight paths over complex terrains
      can inform the location of wind turbines and thereby reduce soaring bird
      mortality.

PMID- 23152763
TI  - Perturbation of chromatin structure globally affects localization and recruitment
      of splicing factors.
AB  - Chromatin structure is an important factor in the functional coupling between
      transcription and mRNA processing, not only by regulating alternative splicing
      events, but also by contributing to exon recognition during constitutive
      splicing. We observed that depolarization of neuroblastoma cell membrane
      potential, which triggers general histone acetylation and regulates alternative
      splicing, causes a concentration of SR proteins in nuclear speckles. This
      prompted us to analyze the effect of chromatin structure on splicing factor
      distribution and dynamics. Here, we show that induction of histone hyper
      acetylation results in the accumulation in speckles of multiple splicing factors
      in different cell types. In addition, a similar effect is observed after
      depletion of the heterochromatic protein HP1alpha, associated with repressive
      chromatin. We used advanced imaging approaches to analyze in detail both the
      structural organization of the speckle compartment and nuclear distribution of
      splicing factors, as well as studying direct interactions between splicing
      factors and their association with chromatin in vivo. The results support a model
      where perturbation of normal chromatin structure decreases the recruitment
      efficiency of splicing factors to nascent RNAs, thus causing their accumulation
      in speckles, which buffer the amount of free molecules in the nucleoplasm. To
      test this, we analyzed the recruitment of the general splicing factor U2AF65 to
      nascent RNAs by iCLIP technique, as a way to monitor early spliceosome assembly.
      We demonstrate that indeed histone hyper-acetylation decreases recruitment of
      U2AF65 to bulk 3' splice sites, coincident with the change in its localization.
      In addition, prior to the maximum accumulation in speckles, ~20% of genes already
      show a tendency to decreased binding, while U2AF65 seems to increase its binding
      to the speckle-located ncRNA MALAT1. All together, the combined imaging and
      biochemical approaches support a model where chromatin structure is essential for
      efficient co-transcriptional recruitment of general and regulatory splicing
      factors to pre-mRNA.

PMID- 23152765
TI  - Sensitive and specific peak detection for SELDI-TOF mass spectrometry using a
      wavelet/neural-network based approach.
AB  - SELDI-TOF mass spectrometer's compact size and automated, high throughput design
      have been attractive to clinical researchers, and the platform has seen steady
      use in biomarker studies. Despite new algorithms and preprocessing pipelines that
      have been developed to address reproducibility issues, visual inspection of the
      results of SELDI spectra preprocessing by the best algorithms still shows
      miscalled peaks and systematic sources of error. This suggests that there
      continues to be problems with SELDI preprocessing. In this work, we study the
      preprocessing of SELDI in detail and introduce improvements. While many
      algorithms, including the vendor supplied software, can identify peak clusters of
      specific mass (or m/z) in groups of spectra with high specificity and low false
      discover rate (FDR), the algorithms tend to underperform estimating the exact
      prevalence and intensity of peaks in those clusters. Thus group differences that
      at first appear very strong are shown, after careful and laborious hand
      inspection of the spectra, to be less than significant. Here we introduce a
      wavelet/neural network based algorithm which mimics what a team of expert, human
      users would call for peaks in each of several hundred spectra in a typical SELDI
      clinical study. The wavelet denoising part of the algorithm optimally smoothes
      the signal in each spectrum according to an improved suite of signal processing
      algorithms previously reported (the LibSELDI toolbox under development). The
      neural network part of the algorithm combines those results with the raw signal
      and a training dataset of expertly called peaks, to call peaks in a test set of
      spectra with approximately 95% accuracy. The new method was applied to data
      collected from a study of cervical mucus for the early detection of cervical
      cancer in HPV infected women. The method shows promise in addressing the ongoing
      SELDI reproducibility issues.

PMID- 23152766
TI  - Feasibility of distributing rapid diagnostic tests for malaria in the retail
      sector: evidence from an implementation study in Uganda.
AB  - BACKGROUND: Despite the benefits of malaria diagnosis, most presumed malaria
      episodes are never tested. A primary reason is the absence of diagnostic tests in
      retail establishments, where many patients seek care. Malaria rapid diagnostic
      tests (RDTs) in drug shops hold promise for guiding appropriate treatment.
      However, retail providers generally lack awareness of RDTs and training to
      administer them. Further, unsubsidized RDTs may be unaffordable to patients and
      unattractive to retailers. This paper reports results from an intervention study
      testing the feasibility of RDT distribution in Ugandan drug shops. METHODS AND
      FINDINGS: 92 drug shops in 58 villages were offered subsidized RDTs for sale
      after completing training. Data on RDT purchases, storage, administration and
      disposal were collected, and samples were sent for quality testing. Household
      surveys were conducted to capture treatment outcomes. Estimated daily RDT sales
      varied substantially across shops, from zero to 8.46 RDTs per days. Overall
      compliance with storage, treatment and disposal guidelines was excellent. All
      RDTs (100%) collected from shops passed quality testing. The median price charged
      for RDTs was 1000USH ($0.40), corresponding to a 100% markup, and the same price
      as blood slides in local health clinics. RDTs affected treatment decisions. RDT
      positive patients were 23 percentage points more likely to buy Artemisinin
      Combination Therapies (ACTs) (p = .005) and 33.1 percentage points more likely to
      buy other antimalarials (p<.001) than RDT-negative patients, and were 5.6
      percentage points more likely to buy ACTs (p = .05) and 31.4 percentage points
      more likely to buy other antimalarials (p<.001) than those not tested at all.
      CONCLUSIONS: Despite some heterogeneity, shops demonstrated a desire to stock
      RDTs and use them to guide treatment recommendations. Most shops stored,
      administered and disposed of RDTs properly and charged mark-ups similar to those
      charged on common medicines. Results from this study suggest that distributing
      RDTs through the retail sector is feasible and can reduce inappropriate treatment
      for suspected malaria.

PMID- 23152767
TI  - No association of the BDNF val66met polymorphism with implicit associative
      vocabulary and motor learning.
AB  - Brain-derived neurotrophic factor (BDNF) has been suggested to play a major role
      in plasticity, neurogenesis and learning in the adult brain. The BDNF gene
      contains a common val66met polymorphism associated with decreased activity
      dependent excretion of BDNF and a potential influence on behaviour, more
      specifically, on motor learning. The objective of this study was to determine the
      influence of the BDNF val66met polymorphism on short-term implicit associative
      learning and whether its influence is cognitive domain-specific (motor vs.
      language). A sample of 38 young healthy participants was genotyped, screened for
      background and neuropsychological differences, and tested with two associative
      implicit learning paradigms in two different cognitive domains, i.e., motor and
      vocabulary learning. Subjects performed the serial reaction time task (SRTT) to
      determine implicit motor learning and a recently established associative
      vocabulary learning task (AVL) for implicit learning of action and object words.
      To determine the influence of the BDNF polymorphism on domain-specific implicit
      learning, behavioural improvements in the two tasks were compared between val/val
      (n = 22) and met carriers (val/met: n = 15 and met/met: n = 1). There was no
      evidence for an impact of the BDNF val66met polymorphism on the behavioural
      outcome in implicit short-term learning paradigms in young healthy subjects.
      Whether this polymorphism plays a relevant role in long-term training paradigms
      or in subjects with impaired neuronal plasticity or reduced learning capacity,
      such as aged individuals, demented patients or patients with brain lesions, has
      to be determined in future studies.

PMID- 23152768
TI  - Denitrification performance and microbial community structure of a combined WLA
      OBCO system.
AB  - The contamination of surface water by nitrogen due to fertilizer application and
      discharge of wastewater is an increasingly serious problem. A multifunctional
      device, which combines water-lifting and aeration (WLA) with oligotrophic
      biological contact oxidation (OBCO), was developed for pretreatment of raw water
      to reduce nitrogen. The performance of nitrogen removal and changes in microbial
      community structure were investigated. The results showed that the combined
      technique of WLA-OBCO was feasible, and that ammonium, nitrate, total nitrogen
      and total organic carbon were effectively removed. Meanwhile, nitrite was mostly
      undetectable. The PCR-DGGE and clone sequencing results revealed that alpha
      proteobacterium was the largest bacterial group, and Pseudomonas strains Y3 and
      J8 were the dominant bacteria.

PMID- 23152769
TI  - Cyclic stretch induces cell reorientation on substrates by destabilizing catch
      bonds in focal adhesions.
AB  - A minimal model of cellular mechanosensing system that consists of a single
      stress fiber adhering on a substrate via two focal adhesions made of catch bonds
      is adopted to investigate the phenomena of cell reorientation on substrates
      induced by an applied uniaxial cyclic stretch. The model indicates that the catch
      bonds in the focal adhesions experience a periodically oscillating internal force
      with amplitude and frequency controlled by two intrinsic clocks of the stress
      fiber, one associated with localized activation and the other with homogeneous
      activation of sarcomere units along the stress fiber. It is shown that this
      oscillating force due to cyclic stretch tends to destabilize focal adhesions by
      reducing the lifetime of catch bonds. The resulting slide or relocation of focal
      adhesions then causes the associated stress fiber to shorten and rotate to
      configurations nearly perpendicular to the stretching direction. These predicted
      behaviors from our model are consistent with a wide range of experimental
      observations.

PMID- 23152770
TI  - Disparities in healthcare utilisation rates for Aboriginal and non-Aboriginal
      Albertan residents, 1997-2006: a population database study.
AB  - BACKGROUND: It is widely recognised that significant discrepancies exist between
      the health of indigenous and non-indigenous populations. Whilst the reasons are
      incompletely defined, one potential cause is that indigenous communities do not
      access healthcare to the same extent. We investigated healthcare utilisation
      rates in the Canadian Aboriginal population to elucidate the contribution of this
      fundamental social determinant for health to such disparities. METHODS:
      Healthcare utilisation data over a nine-year period were analysed for a cohort of
      nearly two million individuals to determine the rates at which Aboriginal and non
      Aboriginal populations utilised two specialties (Cardiology and Ophthalmology) in
      Alberta, Canada. Unadjusted and adjusted healthcare utilisation rates obtained by
      mixed linear and Poisson regressions, respectively, were compared amongst three
      population groups - federally registered Aboriginals, individuals receiving
      welfare, and other Albertans. RESULTS: Healthcare utilisation rates for
      Aboriginals were substantially lower than those of non-Aboriginals and welfare
      recipients at each time point and subspecialty studied [e.g. During 2005/06,
      unadjusted Cardiology utilisation rates were 0.28% (Aboriginal, n = 97,080),
      0.93% (non-Aboriginal, n = 1,720,041) and 1.37% (Welfare, n = 52,514), p =
      <0.001]. The age distribution of the Aboriginal population was markedly different
      [2.7%>=65 years of age, non-Aboriginal 10.7%], and comparable utilisation rates
      were obtained after adjustment for fiscal year and estimated life expectancy
      [Cardiology: Incidence Rate Ratio 0.66, Ophthalmology: IRR 0.85]. DISCUSSION: The
      analysis revealed that Aboriginal people utilised subspecialty healthcare at a
      consistently lower rate than either comparatively economically disadvantaged
      groups or the general population. Notably, the differences were relatively
      invariant between the major provincial centres and over a nine year period.
      Addressing the causes of these discrepancies is essential for reducing marked
      health disparities, and so improving the health of Aboriginal people.

PMID- 23152771
TI  - Org 214007-0: a novel non-steroidal selective glucocorticoid receptor modulator
      with full anti-inflammatory properties and improved therapeutic index.
AB  - Glucocorticoids (GCs) such as prednisolone are potent immunosuppressive drugs but
      suffer from severe adverse effects, including the induction of insulin
      resistance. Therefore, development of so-called Selective Glucocorticoid Receptor
      Modulators (SGRM) is highly desirable. Here we describe a non-steroidal
      Glucocorticoid Receptor (GR)-selective compound (Org 214007-0) with a binding
      affinity to GR similar to that of prednisolone. Structural modelling of the GR
      Org 214007-0 binding site shows disturbance of the loop between helix 11 and
      helix 12 of GR, confirmed by partial recruitment of the TIF2-3 peptide. Using
      various cell lines and primary human cells, we show here that Org 214007-0 acts
      as a partial GC agonist, since it repressed inflammatory genes and was less
      effective in induction of metabolic genes. More importantly, in vivo studies in
      mice indicated that Org 214007-0 retained full efficacy in acute inflammation
      models as well as in a chronic collagen-induced arthritis (CIA) model. Gene
      expression profiling of muscle tissue derived from arthritic mice showed a
      partial activity of Org 214007-0 at an equi-efficacious dosage of prednisolone,
      with an increased ratio in repression versus induction of genes. Finally, in mice
      Org 214007-0 did not induce elevated fasting glucose nor the shift in
      glucose/glycogen balance in the liver seen with an equi-efficacious dose of
      prednisolone. All together, our data demonstrate that Org 214007-0 is a novel
      SGRMs with an improved therapeutic index compared to prednisolone. This class of
      SGRMs can contribute to effective anti-inflammatory therapy with a lower risk for
      metabolic side effects.

PMID- 23152772
TI  - Liraglutide increases FGF-21 activity and insulin sensitivity in high fat diet
      and adiponectin knockdown induced insulin resistance.
AB  - BACKGROUND: Liraglutide is a glucagon-like peptide-1 analogue that stimulates
      insulin secretion and improves beta-cell function. However, it is not clear
      whether liraglutide achieves its glucose lowering effect only by its known
      effects or whether other as yet unknown mechanisms are involved. The aim of this
      study was to examine the effects of liraglutide on Fibroblast growth factor-21
      (FGF-21) activity in High-fat diet (HFD) fed ApoE(-/-) mice with adiponectin
      (Acrp30) knockdown. METHOD: HFD-fed ApoE(-/-) mice were treated with adenovirus
      vectors expressing shAcrp30 to produce insulin resistance. Hyperinsulinemic
      euglycemic clamp studies were performed to evaluate insulin sensitivity of the
      mouse model. QRT-PCR and Western blot were used to measure the mRNA and protein
      expression of the target genes. RESULTS: The combination of HFD, ApoE deficiency,
      and hypoadiponectinemia resulted in an additive effect on insulin resistance. FGF
      21 mRNA expressions in both liver and adipose tissues were significantly
      increased while FGF-21 receptor 1 (FGFR-1) and beta-Klotho mRNA levels in adipose
      tissue, as well as FGFR-1-3 and beta-Klotho mRNA levels in liver were
      significantly decreased in this model. Liraglutide treatment markedly improved
      insulin resistance and increased FGF-21 expression in liver and FGFR-3 in adipose
      tissue, restored beta-Klotho mRNA expression in adipose tissue as well as FGFR-1
      3, beta-Klotho levels and phosphorylation of FGFR1 up to the levels observed in
      control mice in liver. Liraglutide treatment also further increased FGF-21
      proteins in liver and plasma. In addition, as shown by hyperinsulinemic
      euglycemic clamp, liraglutide treatment also markedly improved glucose metabolism
      and insulin sensitivity in these animals. CONCLUSION: These findings demonstrate
      an additive effect of HFD, ApoE deficiency, and adiponectin knockdown on insulin
      resistance and unveil that the regulation of glucose metabolism and insulin
      sensitivity by liraglutide may be partly mediated via increased FGF-21 and its
      receptors action.

PMID- 23152774
TI  - Newtonian versus special-relativistic statistical predictions for low-speed
      scattering.
AB  - The statistical predictions of Newtonian and special-relativistic mechanics,
      which are calculated from an initially Gaussian ensemble of trajectories, are
      compared for a low-speed scattering system. The comparisons are focused on the
      mean dwell time, transmission and reflection coefficients, and the position and
      momentum means and standard deviations. We find that the statistical predictions
      of the two theories do not always agree as conventionally expected. The
      predictions are close if the scattering is non-chaotic but they are radically
      different if the scattering is chaotic and the initial ensemble is well localized
      in phase space. Our result indicates that for low-speed chaotic scattering,
      special-relativistic mechanics must be used, instead of the standard practice of
      using Newtonian mechanics, to obtain empirically-correct statistical predictions
      from an initially well-localized Gaussian ensemble.

PMID- 23152773
TI  - Intra-host diversity and emergence of unique GBV-C viral lineages in HIV infected
      subjects in central China.
AB  - GB virus C (GBV-C), which is highly prevalent among HIV/AIDS, seemed to slow the
      HIV disease progression. The HIV/GBV-C co-infected individuals may represent an
      interesting model for the investigation of the role played by HIV infection
      and/or the immune system in driving the evolution of the GBV-C viral populations.
      The present study investigated the prevalence and population dynamics of GB virus
      C in HIV infected individuals representing 13 geographic regions of Hubei
      Province of China. Approximately 37% of HIV-1 infected individuals were infected
      with GBV-C and genotype 3 is appeared to be predominant. Utilizing the 196
      complete E2 nucleotide sequence data from 10 HIV/GBV-C infected individuals and
      employing coalescence based phylogenetic approaches; the present study has
      investigated the intra-host dynamics of GBV-C. The results revealed patient
      specific unique GBV-C viral lineages and each viral lineage showed the evidence
      of rapid population expansion in respective HIV-1 infected patients, thus
      suggesting HIV-1 was unlikely to have been inhibiting effect on the GBV-C viral
      replication. GBV-C in all patients has experienced intense purifying selection,
      suggesting the GBV-C viral invasion and subsequent expansion within the HIV-1
      infected hosts without any modification of the functional epitopes at their
      membrane protein. The finding of within host GBV-C recombinant sequences
      indicated recombination was one of the significant forces in the evolution and
      divergence of GBV-C.

PMID- 23152775
TI  - The scale of faith based organization participation in health service delivery in
      developing countries: systematic [corrected] review and meta-analysis.
AB  - The extent of faith-based organizations' participation within the overall health
      systems of developing countries is unclear. Recent reports state that faith-based
      organizations play a substantial role in providing healthcare in developing
      countries, cited in some publications as up to 70% of all healthcare services.
      The data behind these numbers are sometimes difficult to pinpoint and seem at
      odds to national and regional survey data. In an effort to quantify the
      contribution of faith-based organizations to healthcare delivery in low- and
      middle-income countries, we undertook a systematic review of the literature and
      conducted a new analysis of relevant Demographic and Health Survey data from 47
      countries. Our findings demonstrate that the magnitude of healthcare provided by
      faith-based organizations may be lower than previously estimated. Understanding
      the scale of FBO-provided medical care is important for health sector planning,
      and more accurate and complete estimates are needed.

PMID- 23152776
TI  - Micro-arrayed human embryonic stem cells-derived cardiomyocytes for in vitro
      functional assay.
AB  - INTRODUCTION: The heart is one of the least regenerative organs in the body and
      any major insult can result in a significant loss of heart cells. The development
      of an in vitro-based cardiac tissue could be of paramount importance for many
      aspects of the cardiology research. In this context, we developed an in vitro
      assay based on human cardiomyocytes (hCMs) and ad hoc micro-technologies,
      suitable for several applications: from pharmacological analysis to physio
      phatological studies on transplantable hCMs. We focused on the development of an
      assay able to analyze not only hCMs viability, but also their functionality.
      METHODS: hCMs were cultured onto a poly-acrylamide hydrogel with tunable tissue
      like mechanical properties and organized through micropatterning in a 20*20
      array. Arrayed hCMs were characterized by immunofluorescence, GAP-FRAP analyses
      and live and dead assay. Their functionality was evaluated monitoring the
      excitation-contraction coupling. RESULTS: Micropatterned hCMs maintained the
      expression of the major cardiac markers (cTnT, cTnI, Cx43, Nkx2.5, alpha-actinin)
      and functional properties. The spontaneous contraction frequency was (0.83+/-0.2)
      Hz, while exogenous electrical stimulation lead to an increase up to 2 Hz. As
      proof of concept that our device can be used for screening the effects of
      pathological conditions, hCMs were exposed to increasing levels of H(2)O(2).
      Remarkably, hCMs viability was not compromised with exposure to 0.1 mM H(2)O(2),
      but hCMs contractility was dramatically suppressed. As proof of concept, we also
      developed a microfluidic platform to selectively treat areas of the cell array,
      in the perspective of performing multi-parametric assay. CONCLUSIONS: Such system
      could be a useful tool for testing the effects of multiple conditions on an in
      vitro cell model representative of human heart physiology, thus potentially
      helping the processes of therapy and drug development.

PMID- 23152777
TI  - Molecular characterization of chronic lymphocytic leukemia patients with a high
      number of losses in 13q14.
AB  - BACKGROUND: Patients with chronic lymphocytic leukemia and 13q deletion as their
      only FISH abnormality could have a different outcome depending on the number of
      cells displaying this aberration. Thus, cases with a high number of 13q- cells
      (13q-H) had both shorter overall survival and time to first therapy. The goal of
      the study was to analyze the genetic profile of 13q-H patients. DESIGN AND
      METHODS: A total of 102 samples were studied, 32 of which served as a validation
      cohort and five were healthy donors. RESULTS: Chronic lymphocytic leukemia
      patients with higher percentages of 13q- cells (>80%) showed a different level of
      gene expression as compared to patients with lower percentages (<80%, 13q-L).
      This deregulation affected genes involved in apoptosis and proliferation (BCR and
      NFkB signaling), leading to increased proliferation and decreased apoptosis in
      13q-H patients. Deregulation of several microRNAs, such as miR-15a, miR-155, miR
      29a and miR-223, was also observed in these patients. In addition, our study also
      suggests that the gene expression pattern of 13q-H cases could be similar to the
      patients with 11q- or 17p-. CONCLUSIONS: This study provides new evidence
      regarding the heterogeneity of 13q deletion in chronic lymphocytic leukemia
      patients, showing that apoptosis, proliferation as well as miRNA regulation are
      involved in cases with higher percentages of 13q- cells.

PMID- 23152778
TI  - Establishment and characterization of a highly tumourigenic and cancer stem cell
      enriched pancreatic cancer cell line as a well defined model system.
AB  - Standard cancer cell lines do not model the intratumoural heterogeneity situation
      sufficiently. Clonal selection leads to a homogeneous population of cells by
      genetic drift. Heterogeneity of tumour cells, however, is particularly critical
      for therapeutically relevant studies, since it is a prerequisite for acquiring
      drug resistance and reoccurrence of tumours. Here, we report the isolation of a
      highly tumourigenic primary pancreatic cancer cell line, called JoPaca-1 and its
      detailed characterization at multiple levels. Implantation of as few as 100
      JoPaca-1 cells into immunodeficient mice gave rise to tumours that were
      histologically very similar to the primary tumour. The high heterogeneity of
      JoPaca-1 was reflected by diverse cell morphology and a substantial number of
      chromosomal aberrations. Comparative whole-genome sequencing of JoPaca-1 and BxPC
      3 revealed mutations in genes frequently altered in pancreatic cancer.
      Exceptionally high expression of cancer stem cell markers and a high clonogenic
      potential in vitro and in vivo was observed. All of these attributes make this
      cell line an extremely valuable model to study the biology of and pharmaceutical
      effects on pancreatic cancer.

PMID- 23152779
TI  - A noninvasive method to determine the fate of Fe(3)O(4) nanoparticles following
      intravenous injection using scanning SQUID biosusceptometry.
AB  - Magnetic nanoparticles (MNPs) of Fe(3)O(4) have been widely applied in many
      medical fields, but few studies have clearly shown the outcome of particles
      following intravenous injection. We performed a magnetic examination using
      scanning SQUID biosusceptometry (SSB). Based on the results of SSB analysis and
      those of established in vitro nonmagnetic bioassays, this study proposes a model
      of MNP metabolism consisting of an acute metabolic phase with an 8 h duration
      that is followed by a chronic metabolic phase that continues for 28 d following
      MNP injection. The major features included the delivery of the MNPs to the heart
      and other organs, the biodegradation of the MNPs in organs rich with macrophages,
      the excretion of iron metabolites in the urine, and the recovery of the iron load
      from the liver and the spleen. Increases in serum iron levels following MNP
      injection were accompanied by increases in the level of transferrin in the serum
      and the number of circulating red blood cells. Correlations between the in vivo
      and in vitro test results indicate the feasibility of using SSB examination for
      the measurement of MNP concentrations, implying future clinical applications of
      SSB for monitoring the hematological effects of MNP injection.

PMID- 23152780
TI  - A novel real-time PCR assay of microRNAs using S-Poly(T), a specific oligo(dT)
      reverse transcription primer with excellent sensitivity and specificity.
AB  - BACKGROUND: MicroRNAs (miRNAs) are small, non-coding RNAs capable of
      postranscriptionally regulating gene expression. Accurate expression profiling is
      crucial for understanding the biological roles of miRNAs, and exploring them as
      biomarkers of diseases. METHODOLOGY/PRINCIPAL FINDINGS: A novel, highly
      sensitive, and reliable miRNA quantification approach,termed S-Poly(T) miRNA
      assay, is designed. In this assay, miRNAs are subjected to polyadenylation and
      reverse transcription with a S-Poly(T) primer that contains a universal reverse
      primer, a universal Taqman probe, an oligo(dT)(11) sequence and six miRNA
      specific bases. Individual miRNAs are then amplified by a specific forward primer
      and a universal reverse primer, and the PCR products are detected by a universal
      Taqman probe. The S-Poly(T) assay showed a minimum of 4-fold increase in
      sensitivity as compared with the stem-loop or poly(A)-based methods. A remarkable
      specificity in discriminating among miRNAs with high sequence similarity was also
      obtained with this approach. Using this method, we profiled miRNAs in human
      pulmonary arterial smooth muscle cells (HPASMC) and identified 9 differentially
      expressed miRNAs associated with hypoxia treatment. Due to its outstanding
      sensitivity, the number of circulating miRNAs from normal human serum was
      significantly expanded from 368 to 518. CONCLUSIONS/SIGNIFICANCE: With excellent
      sensitivity, specificity, and high-throughput, the S-Poly(T) method provides a
      powerful tool for miRNAs quantification and identification of tissue- or disease
      specific miRNA biomarkers.

PMID- 23152781
TI  - Differential regulation of amyloid precursor protein/presenilin 1 interaction
      during Abeta40/42 [corrected] production detected using fusion constructs.
AB  - Beta amyloid peptides (Abeta) play a key role in the pathogenesis of Alzheimer
      disease (AD). Presenilins (PS) function as the catalytic subunits of gamma
      secretase, the enzyme that releases Abeta from ectodomain cleaved amyloid
      precursor protein (APP) by intramembrane proteolysis. Familial Alzheimer disease
      (FAD)-linked PSEN mutations alter APP processing in a manner that increases the
      relative abundance of longer Abeta42 peptides to that of Abeta40 peptides. The
      mechanisms by which Abeta40 and Abeta42 peptides are produced in a ratio of ten
      to one by wild type presenilin (PS) and by which Abeta42 is overproduced by FAD
      linked PS variants are not completely understood. We generated chimeras of the
      amyloid precursor protein C-terminal fragment (C99) and PS to address this issue.
      We found a chimeric protein where C99 is fused to the PS1 N-terminus undergoes in
      cis processing to produce Abeta and that a fusion protein harboring FAD-linked
      PS1 mutations overproduced Abeta42. To change the molecular interactions within
      the C99-PS1 fusion protein, we made sequential deletions of the junction between
      C99 and PS1. We found differential effects of deletion in C99-PS1 on Abeta40 and
      42 production. Deletion of the junction between APP CTF and PS1 in the fusion
      protein decreased Abeta40, while it did not decrease Abeta42 production in the
      presence or absence of FAD-linked PS1 mutation. These results are consistent with
      the idea that the APP/PS interaction is differentially regulated during Abeta40
      and 42 production.

PMID- 23152782
TI  - Knockdown of Ki-67 by dicer-substrate small interfering RNA sensitizes bladder
      cancer cells to curcumin-induced tumor inhibition.
AB  - Transitional cell carcinoma (TCC) of the urinary bladder is the most common
      cancer of the urinary tract. Most of the TCC cases are of the superficial type
      and are treated with transurethral resection (TUR). However, the recurrence rate
      is high and the current treatments have the drawback of inducing strong systemic
      toxicity or cause painful cystitis. Therefore, it would be of therapeutic value
      to develop novel concepts and identify novel drugs for the treatment of bladder
      cancer. Ki-67 is a large nucleolar phosphoprotein whose expression is tightly
      linked to cell proliferation, and curcumin, a phytochemical derived from the
      rhizome Curcuma longa, has been shown to possess powerful anticancer properties.
      In this study, we evaluated the combined efficacy of curcumin and a siRNA against
      Ki-67 mRNA (Ki-67-7) in rat (AY-27) and human (T-24) bladder cancer cells. The
      anticancer effects were assessed by the determination of cell viability,
      apoptosis and cell cycle analysis. Ki-67-7 (10 nM) and curcumin (10 uM), when
      treated independently, were moderately effective. However, in their combined
      presence, proliferation of bladder cancer cells was profoundly (>85%) inhibited;
      the rate of apoptosis in the combined presence of curcumin and Ki-67-7 (36%) was
      greater than that due to Ki-67-7 (14%) or curcumin (13%) alone. A similar synergy
      between curcumin and Ki-67-7 in inducing cell cycle arrest was also observed.
      Western blot analysis suggested that pretreatment with Ki-67-7 sensitized bladder
      cancer cells to curcumin-mediated apoptosis and cell cycle arrest by p53- and p21
      independent mechanisms. These data suggest that a combination of anti-Ki-67 siRNA
      and curcumin could be a viable treatment against the proliferation of bladder
      cancer cells.

PMID- 23152783
TI  - Impaired contingent attentional capture predicts reduced working memory capacity
      in schizophrenia.
AB  - Although impairments in working memory (WM) are well documented in schizophrenia,
      the specific factors that cause these deficits are poorly understood. In this
      study, we hypothesized that a heightened susceptibility to attentional capture at
      an early stage of visual processing would result in working memory encoding
      problems. 30 patients with schizophrenia and 28 demographically matched healthy
      participants were presented with a search array and asked to report the
      orientation of the target stimulus. In some of the trials, a flanker stimulus
      preceded the search array that either matched the color of the target (relevant
      flanker capture) or appeared in a different color (irrelevant-flanker capture).
      Working memory capacity was determined in each individual using the visual change
      detection paradigm. Patients needed considerably more time to find the target in
      the no-flanker condition. After adjusting the individual exposure time, both
      groups showed equivalent capture costs in the irrelevant-flanker condition.
      However, in the relevant-flanker condition, capture costs were increased in
      patients compared to controls when the stimulus onset asynchrony between the
      flanker and the search array was high. Moreover, the increase in relevant capture
      costs correlated negatively with working memory capacity. This study demonstrates
      preserved stimulus-driven attentional capture but impaired contingent attentional
      capture associated with low working memory capacity in schizophrenia. These
      findings suggest a selective impairment of top-down attentional control in
      schizophrenia, which may impair working memory encoding.

PMID- 23152784
TI  - Transcriptional regulation of the Ufm1 conjugation system in response to
      disturbance of the endoplasmic reticulum homeostasis and inhibition of vesicle
      trafficking.
AB  - Homeostasis of the endoplasmic reticulum (ER) is essential for normal cellular
      functions. Disturbance of this homeostasis causes ER stress and activates the
      Unfolded Protein Response (UPR). The Ufm1 conjugation system is a novel Ubiquitin
      like (Ubl) system whose physiological target(s) and biological functions remain
      largely undefined. Genetic study has demonstrated that the Ufm1-activating enzyme
      Uba5 is indispensible for erythroid differentiation in mice, highlighting the
      importance of this novel system in animal development. In this report we present
      the evidence for involvement of RCAD/Ufl1, a putative Ufm1-specific E3 ligase,
      and its binding partner C53/LZAP protein in ufmylation of endogenous Ufm1
      targets. Moreover, we found that the Ufm1 system was transcriptionally up
      regulated by disturbance of the ER homeostasis and inhibition of vesicle
      trafficking. Using luciferase reporter and ChIP assays, we dissected the Ufm1
      promoter and found that Ufm1 was a potential target of Xbp-1, one of crucial
      transcription factors in UPR. We further examined the effect of Xbp-1 deficiency
      on the expression of the Ufm1 components. Interestingly, the expression of Ufm1,
      Uba5, RCAD/Ufl1 and C53/LZAP in wild-type mouse embryonic fibroblasts (MEFs) was
      significantly induced by inhibition of vesicle trafficking, but the induction was
      negated by Xbp-1 deficiency. Finally, we found that knockdown of the Ufm1 system
      in U2OS cells triggered UPR and amplification of the ER network. Taken together,
      our study provided critical insight into the regulatory mechanism of the Ufm1
      system and established a direct link between this novel Ubl system and the ER
      network.

PMID- 23152785
TI  - LDx: estimation of linkage disequilibrium from high-throughput pooled
      resequencing data.
AB  - High-throughput pooled resequencing offers significant potential for whole genome
      population sequencing. However, its main drawback is the loss of haplotype
      information. In order to regain some of this information, we present LDx, a
      computational tool for estimating linkage disequilibrium (LD) from pooled
      resequencing data. LDx uses an approximate maximum likelihood approach to
      estimate LD (r(2)) between pairs of SNPs that can be observed within and among
      single reads. LDx also reports r(2) estimates derived solely from observed
      genotype counts. We demonstrate that the LDx estimates are highly correlated with
      r(2) estimated from individually resequenced strains. We discuss the performance
      of LDx using more stringent quality conditions and infer via simulation the
      degree to which performance can improve based on read depth. Finally we
      demonstrate two possible uses of LDx with real and simulated pooled resequencing
      data. First, we use LDx to infer genomewide patterns of decay of LD with physical
      distance in D. melanogaster population resequencing data. Second, we demonstrate
      that r(2) estimates from LDx are capable of distinguishing alternative
      demographic models representing plausible demographic histories of D.
      melanogaster.

PMID- 23152786
TI  - Genetic and infectious profiles of Japanese multiple sclerosis patients.
AB  - BACKGROUND: Nationwide surveys conducted in Japan over the past thirty years have
      revealed a four-fold increase in the estimated number of multiple sclerosis (MS)
      patients, a decrease in the age at onset, and successive increases in patients
      with conventional MS, which shows an involvement of multiple sites in the central
      nervous system, including the cerebrum and cerebellum. We aimed to clarify
      whether genetic and infectious backgrounds correlate to distinct disease
      phenotypes of MS in Japanese patients. METHODOLOGY/PRINCIPAL FINDINGS: We
      analyzed HLA-DRB1 and -DPB1 alleles, and IgG antibodies specific for Helicobacter
      pylori, Chlamydia pneumoniae, varicella zoster virus, and Epstein-Barr virus
      nuclear antigen (EBNA) in 145 MS patients and 367 healthy controls (HCs).
      Frequencies of DRB1*0405 and DPB1*0301 were significantly higher, and DRB1*0901
      and DPB1*0401 significantly lower, in MS patients as compared with HCs. MS
      patients with DRB1*0405 had a significantly earlier age of onset and lower
      Progression Index than patients without this allele. The proportion and absolute
      number of patients with DRB1*0405 successively increased with advancing year of
      birth. In MS patients without DRB1*0405, the frequency of the DRB1*1501 allele
      was significantly higher, while the DRB1*0901 allele was significantly lower,
      compared with HCs. Furthermore, DRB1*0405-negative MS patients were significantly
      more likely to be positive for EBNA antibodies compared with HCs. CONCLUSIONS:
      Our study suggests that MS patients harboring DRB1*0405, a genetic risk factor
      for MS in the Japanese population, have a younger age at onset and a relatively
      benign disease course, while DRB1*0405-negative MS patients have features similar
      to Western-type MS in terms of association with Epstein-Barr virus infection and
      DRB1*1501. The recent increase of MS in young Japanese people may be caused, in
      part, by an increase in DRB1*0405-positive MS patients.

PMID- 23152787
TI  - Human trifunctional protein alpha links cardiolipin remodeling to beta-oxidation.
AB  - Cardiolipin (CL) is a mitochondrial membrane phospholipid which plays a key role
      in apoptosis and supports mitochondrial respiratory chain complexes involved in
      the generation of ATP. In order to facilitate its role CL must be remodeled with
      appropriate fatty acids. We previously identified a human monolysocardiolipin
      acyltransferase activity which remodels CL via acylation of monolysocardiolipin
      (MLCL) to CL and was identical to the alpha subunit of trifunctional protein
      (alphaTFP) lacking the first 227 amino acids. Full length alphaTFP is an enzyme
      that plays a prominent role in mitochondrial beta-oxidation, and in this study we
      assessed the role, if any, which this metabolic enzyme plays in the remodeling of
      CL. Purified human recombinant alphaTFP exhibited acyl-CoA acyltransferase
      activity in the acylation of MLCL to CL with linoleoyl-CoA, oleoyl-CoA and
      palmitoyl-CoA as substrates. Expression of alphaTFP increased radioactive
      linoleate or oleate or palmitate incorporation into CL in HeLa cells. Expression
      of alphaTFP in Barth Syndrome lymphoblasts, which exhibit reduced tetralinoleoyl
      CL, elevated linoleoyl-CoA acylation of MLCL to CL in vitro, increased
      mitochondrial respiratory Complex proteins and increased linoleate-containing
      species of CL. Knock down of alphaTFP in Barth Syndrome lymphoblasts resulted in
      greater accumulation of MLCL than those with normal alphaTFP levels. The results
      clearly indicate that the human alphaTFP exhibits MLCL acyltransferase activity
      for the resynthesis of CL from MLCL and directly links an enzyme of mitochondrial
      beta-oxidation to CL remodeling.

PMID- 23152788
TI  - Mineral distributions at the developing tendon enthesis.
AB  - Tendon attaches to bone across a functionally graded interface, "the enthesis". A
      gradient of mineral content is believed to play an important role for dissipation
      of stress concentrations at mature fibrocartilaginous interfaces. Surgical repair
      of injured tendon to bone often fails, suggesting that the enthesis does not
      regenerate in a healing setting. Understanding the development and the micro/nano
      meter structure of this unique interface may provide novel insights for the
      improvement of repair strategies. This study monitored the development of
      transitional tissue at the murine supraspinatus tendon enthesis, which begins
      postnatally and is completed by postnatal day 28. The micrometer-scale
      distribution of mineral across the developing enthesis was studied by X-ray micro
      computed tomography and Raman microprobe spectroscopy. Analyzed regions were
      identified and further studied by histomorphometry. The nanometer-scale
      distribution of mineral and collagen fibrils at the developing interface was
      studied using transmission electron microscopy (TEM). A zone (~20 um) exhibiting
      a gradient in mineral relative to collagen was detected at the leading edge of
      the hard-soft tissue interface as early as postnatal day 7. Nanocharacterization
      by TEM suggested that this mineral gradient arose from intrinsic surface
      roughness on the scale of tens of nanometers at the mineralized front.
      Microcomputed tomography measurements indicated increases in bone mineral density
      with time. Raman spectroscopy measurements revealed that the mineral-to-collagen
      ratio on the mineralized side of the interface was constant throughout postnatal
      development. An increase in the carbonate concentration of the apatite mineral
      phase over time suggested possible matrix remodeling during postnatal
      development. Comparison of Raman-based observations of localized mineral content
      with histomorphological features indicated that development of the graded
      mineralized interface is linked to endochondral bone formation near the tendon
      insertion. These conserved and time-varying aspects of interface composition may
      have important implications for the growth and mechanical stability of the tendon
      to-bone attachment throughout development.

PMID- 23152789
TI  - On the specificity of heparin/heparan sulfate binding to proteins. Anion-binding
      sites on antithrombin and thrombin are fundamentally different.
AB  - BACKGROUND: The antithrombin-heparin/heparan sulfate (H/HS) and thrombin-H/HS
      interactions are recognized as prototypic specific and non-specific
      glycosaminoglycan (GAG)-protein interactions, respectively. The fundamental
      structural basis for the origin of specificity, or lack thereof, in these
      interactions remains unclear. The availability of multiple co-crystal structures
      facilitates a structural analysis that challenges the long-held belief that the
      GAG binding sites in antithrombin and thrombin are essentially similar with high
      solvent exposure and shallow surface characteristics. METHODOLOGY: Analyses of
      solvent accessibility and exposed surface areas, gyrational mobility, symmetry,
      cavity shape/size, conserved water molecules and crystallographic parameters were
      performed for 12 X-ray structures, which include 12 thrombin and 16 antithrombin
      chains. Novel calculations are described for gyrational mobility and prediction
      of water loci and conservation. RESULTS: The solvent accessibilities and
      gyrational mobilities of arginines and lysines in the binding sites of the two
      proteins reveal sharp contrasts. The distribution of positive charges shows
      considerable asymmetry in antithrombin, but substantial symmetry for thrombin.
      Cavity analyses suggest the presence of a reasonably sized bifurcated cavity in
      antithrombin that facilitates a firm 'hand-shake' with H/HS, but with thrombin, a
      weaker 'high-five'. Tightly bound water molecules were predicted to be localized
      in the pentasaccharide binding pocket of antithrombin, but absent in thrombin.
      Together, these differences in the binding sites explain the major H/HS
      recognition characteristics of the two prototypic proteins, thus affording an
      explanation of the specificity of binding. This provides a foundation for
      understanding specificity of interaction at an atomic level, which will greatly
      aid the design of natural or synthetic H/HS sequences that target proteins in a
      specific manner.

PMID- 23152790
TI  - Targeting the acute promyelocytic leukemia-associated fusion proteins
      PML/RARalpha and PLZF/RARalpha with interfering peptides.
AB  - In acute promyelocytic leukemia (APL), hematopoietic differentiation is blocked
      and immature blasts accumulate in the bone marrow and blood. APL is associated
      with chromosomal aberrations, including t(15;17) and t(11;17). For these two
      translocations, the retinoic acid receptor alpha (RARalpha) is fused to the
      promyelocytic leukemia (PML) gene or the promyelocytic zinc finger (PLZF) gene,
      respectively. Both fusion proteins lead to the formation of a high-molecular
      weight complex. High-molecular-weight complexes are caused by the "coiled-coil"
      domain of PML or the BTB/POZ domain of PLZF. PML/RARalpha without the "coiled
      coil" fails to block differentiation and mediates an all-trans retinoic acid
      response. Similarly, mutations in the BTB/POZ domain disrupt the high-molecular
      weight complex, abolishing the leukemic potential of PLZF/RARalpha. Specific
      interfering polypeptides were used to target the oligomerization domain of
      PML/RARalpha or PLZF/RARalpha. PML/RARalpha and PLZF/RARalpha were analyzed for
      the ability to form high-molecular-weight complexes, the protein stability and
      the potential to induce a leukemic phenotype in the presence of the interfering
      peptides. Expression of these interfering peptides resulted in a reduced
      replating efficiency and overcame the differentiation block induced by
      PML/RARalpha and PLZF/RARalpha in murine hematopoietic stem cells. This
      expression also destabilized the PLZF/RARalpha-induced high-molecular-weight
      complex formation and caused the degradation of the fusion protein. Targeting
      fusion proteins through interfering peptides is a promising approach to further
      elucidate the biology of leukemia.

PMID- 23152791
TI  - Nucleo-cytoplasmic trafficking of TRIM8, a novel oncogene, is involved in
      positive regulation of TNF induced NF-kappaB pathway.
AB  - TNF induced nuclear factor kappa B (NF-kappaB) is one of the central signaling
      pathways that plays a critical role in carcinogenesis and inflammatory diseases.
      Post-translational modification through ubiquitin plays important role in the
      regulation of this pathway. In the current study, we investigated the role of
      TRIM8, member of RING family ubiquitin ligase in regulation of NF-kappaB pathway.
      We observed that TRIM8 positively regulates TNF induced NF-kappaB pathway.
      Different domains of TRIM8 showed discrete functions at the different steps in
      regulation of TNF induced NF-kappaB pathway. Ubiquitin ligase activity of TRIM8
      is essential for regulation of NF-kappaB activation in both cytoplasm as well as
      nucleus. TRIM8 negates PIAS3 mediated negative repression of NF-kappaB at p65 by
      inducing translocation of PIAS3 from nucleus to cytoplasm as well as its
      turnover. TNF induces translocation of TRIM8 from nucleus to cytoplasm, which
      positively regulates NF-kappaB. The cytoplasmic translocation of TRIM8 is
      essential for TNF induced NF-kappaB but not for p65 mediated NF-kappaB
      regulation. TRIM8 also enhanced the clonogenic and migration ability of cells by
      modulating NF-kappaB. The further study will help to understand the role of TRIM8
      in inflammation and cancer.

PMID- 23152792
TI  - Smart markers for watershed-based cell segmentation.
AB  - Automated cell imaging systems facilitate fast and reliable analysis of
      biological events at the cellular level. In these systems, the first step is
      usually cell segmentation that greatly affects the success of the subsequent
      system steps. On the other hand, similar to other image segmentation problems,
      cell segmentation is an ill-posed problem that typically necessitates the use of
      domain-specific knowledge to obtain successful segmentations even by human
      subjects. The approaches that can incorporate this knowledge into their
      segmentation algorithms have potential to greatly improve segmentation results.
      In this work, we propose a new approach for the effective segmentation of live
      cells from phase contrast microscopy. This approach introduces a new set of
      "smart markers" for a marker-controlled watershed algorithm, for which the
      identification of its markers is critical. The proposed approach relies on using
      domain-specific knowledge, in the form of visual characteristics of the cells, to
      define the markers. We evaluate our approach on a total of 1,954 cells. The
      experimental results demonstrate that this approach, which uses the proposed
      definition of smart markers, is quite effective in identifying better markers
      compared to its counterparts. This will, in turn, be effective in improving the
      segmentation performance of a marker-controlled watershed algorithm.

PMID- 23152793
TI  - Development and validation of a job exposure matrix for physical risk factors in
      low back pain.
AB  - OBJECTIVES: The aim was to construct and validate a gender-specific job exposure
      matrix (JEM) for physical exposures to be used in epidemiological studies of low
      back pain (LBP). MATERIALS AND METHODS: We utilized two large Finnish population
      surveys, one to construct the JEM and another to test matrix validity. The
      exposure axis of the matrix included exposures relevant to LBP (heavy physical
      work, heavy lifting, awkward trunk posture and whole body vibration) and
      exposures that increase the biomechanical load on the low back (arm elevation) or
      those that in combination with other known risk factors could be related to LBP
      (kneeling or squatting). Job titles with similar work tasks and exposures were
      grouped. Exposure information was based on face-to-face interviews. Validity of
      the matrix was explored by comparing the JEM (group-based) binary measures with
      individual-based measures. The predictive validity of the matrix against LBP was
      evaluated by comparing the associations of the group-based (JEM) exposures with
      those of individual-based exposures. RESULTS: The matrix includes 348 job titles,
      representing 81% of all Finnish job titles in the early 2000s. The specificity of
      the constructed matrix was good, especially in women. The validity measured with
      kappa-statistic ranged from good to poor, being fair for most exposures. In men,
      all group-based (JEM) exposures were statistically significantly associated with
      one-month prevalence of LBP. In women, four out of six group-based exposures
      showed an association with LBP. CONCLUSIONS: The gender-specific JEM for physical
      exposures showed relatively high specificity without compromising sensitivity.
      The matrix can therefore be considered as a valid instrument for exposure
      assessment in large-scale epidemiological studies, when more precise but more
      labour-intensive methods are not feasible. Although the matrix was based on
      Finnish data we foresee that it could be applicable, with some modifications, in
      other countries with a similar level of technology.

PMID- 23152794
TI  - Biochemical characterization of Anopheles gambiae SRPN6, a malaria parasite
      invasion marker in mosquitoes.
AB  - Serine proteinase inhibitors of the serpin family are well known as negative
      regulators of hemostasis, thrombolysis and innate immune responses. Additionally,
      non-inhibitory serpins serve functions as chaperones, hormone transporters, or
      anti-angiogenic factors. In the African malaria mosquito, Anopheles gambiae s.s.,
      at least three serpins (SRPNs) are implicated in the innate immune response
      against malaria parasites. Based on reverse genetic and cell biological analyses,
      AgSRPN6 limits parasite numbers and transmission and has been postulated to
      control melanization and complement function in mosquitoes. This study aimed to
      characterize AgSRPN6 biophysically and determine its biochemical mode of action.
      The structure model of AgSRPN6, as predicted by I-Tasser showed the protein in
      the native serpin fold, with three central beta-sheets, nine surrounding alpha
      helices, and a protruding reactive center loop. This structure is in agreement
      with biophysical and functional data obtained from recombinant (r) AgSRPN6,
      produced in Escherichia coli. The physical properties of purified rAgSRPN6 were
      investigated by means of analytical ultracentrifugation, circular dichroism, and
      differential scanning calorimetry tools. The recombinant protein exists
      predominantly as a monomer in solution, is composed of a mixture of alpha-helices
      and beta-sheets, and has a mid-point unfolding temperature of 56 degrees C.
      Recombinant AgSRPN6 strongly inhibited porcine pancreatic kallikrein and to a
      lesser extent bovine pancreatic trypsin in vitro. Furthermore, rAgSRPN6 formed
      inhibitory, SDS-stable, higher molecular weight complexes with prophenoloxidase
      activating proteinase (PAP)1, PAP3, and Hemolymph protein (HP)6, which are
      required for melanization in the lepidopteran model organism, Manduca sexta.
      Taken together, our results strongly suggest that AgSRPN6 takes on a native
      serpin fold and is an inhibitor of trypsin-like serine proteinases.

PMID- 23152795
TI  - Repellents inhibit P450 enzymes in Stegomyia (Aedes) aegypti.
AB  - The primary defence against mosquitoes and other disease vectors is often the
      application of a repellent. Despite their common use, the mechanism(s) underlying
      the activity of repellents is not fully understood, with even the mode of action
      of DEET having been reported to be via different mechanisms; e.g. interference
      with olfactory receptor neurones or actively detected by olfactory receptor
      neurones on the antennae or maxillary palps. In this study, we discuss a novel
      mechanism for repellence, one of P450 inhibition. Thirteen essential oil extracts
      from Colombian plants were assayed for potency as P450 inhibitors, using a
      kinetic fluorometric assay, and for repellency using a modified World Health
      Organisation Pesticide Evaluations Scheme (WHOPES) arm-in cage assay with
      Stegomyia (Aedes) aegypti mosquitoes. Bootstrap analysis on the inhibition
      analysis revealed a significant correlation between P450-inhibition and repellent
      activity of the oils.

PMID- 23152796
TI  - Efficient prediction of co-complexed proteins based on coevolution.
AB  - The prediction of the network of protein-protein interactions (PPI) of an
      organism is crucial for the understanding of biological processes and for the
      development of new drugs. Machine learning methods have been successfully applied
      to the prediction of PPI in yeast by the integration of multiple direct and
      indirect biological data sources. However, experimental data are not available
      for most organisms. We propose here an ensemble machine learning approach for the
      prediction of PPI that depends solely on features independent from experimental
      data. We developed new estimators of the coevolution between proteins and
      combined them in an ensemble learning procedure.We applied this method to a
      dataset of known co-complexed proteins in Escherichia coli and compared it to
      previously published methods. We show that our method allows prediction of PPI
      with an unprecedented precision of 95.5% for the first 200 sorted pairs of
      proteins compared to 28.5% on the same dataset with the previous best method.A
      close inspection of the best predicted pairs allowed us to detect new or recently
      discovered interactions between chemotactic components, the flagellar apparatus
      and RNA polymerase complexes in E. coli.

PMID- 23152797
TI  - Pre-, per- and postoperative factors affecting performance of postlinguistically
      deaf adults using cochlear implants: a new conceptual model over time.
AB  - OBJECTIVE: To test the influence of multiple factors on cochlear implant (CI)
      speech performance in quiet and in noise for postlinguistically deaf adults, and
      to design a model of predicted auditory performance with a CI as a function of
      the significant factors. STUDY DESIGN: Retrospective multi-centre study. METHODS:
      Data from 2251 patients implanted since 2003 in 15 international centres were
      collected. Speech scores in quiet and in noise were converted into percentile
      ranks to remove differences between centres. The influence of 15 pre-, per- and
      postoperative factors, such as the duration of moderate hearing loss (mHL), the
      surgical approach (cochleostomy or round window approach), the angle of
      insertion, the percentage of active electrodes, and the brand of device were
      tested. The usual factors, duration of profound HL (pHL), age, etiology, duration
      of CI experience, that are already known to have an influence, were included in
      the statistical analyses. RESULTS: The significant factors were: the pure tone
      average threshold of the better ear, the brand of device, the percentage of
      active electrodes, the use of hearing aids (HAs) during the period of pHL, and
      the duration of mHL. CONCLUSIONS: A new model was designed showing a decrease of
      performance that started during the period of mHL, and became faster during the
      period of pHL. The use of bilateral HAs slowed down the related central
      reorganization that is the likely cause of the decreased performance.

PMID- 23152798
TI  - Transient transfection of a wild-type p53 gene triggers resveratrol-induced
      apoptosis in cancer cells.
AB  - Resveratrol is a promising chemopreventive agent that mediates many cellular
      targets involved in cancer signaling pathways. p53 has been suggested to play a
      role in the anticancer properties of resveratrol. We investigated resveratrol
      induced cytotoxicity in H1299 cells, which are non-small lung cancer cells that
      have a partial deletion of the gene that encodes the p53 protein. The results for
      H1299 cells were compared with those for three cell lines that constitutively
      express wild-type p53: breast cancer MCF-7, adenocarcinomic alveolar basal
      epithelia A549 and non-small lung cancer H460. Cell viability assays revealed
      that resveratrol reduced the viability of all four of these cell lines in a dose-
      and time-dependent manner. MCF-7, A549 and H460 cells were more sensitive to
      resveratrol than were H1299 cells when exposed to the drug for 24 h at
      concentrations above 100 uM. Resveratrol also increased the p53 protein levels in
      MCF-7 cells without altering the p53 mRNA levels, suggesting a post-translational
      modulation of the protein. The resveratrol-induced cytotoxicity in these cells
      was partially mediated by p53 and involved the activation of caspases 9 and 7 and
      the cleavage of PARP. In H1299 cells, resveratrol-induced cytotoxicity was less
      pronounced and (in contrast to MCF-7 cells) cell death was not accompanied by
      caspase activation. These findings are consistent with the observation that MCF-7
      cells were positively labeled by TUNEL following exposure to 100 uM resveratrol
      whereas H1299 cells under similar conditions were not labeled by TUNEL. The
      transient transfection of a wild-type p53-GFP gene caused H1299 cells to become
      more responsive to the pro-apoptotic properties of resveratrol, similarly to
      findings in the p53-positive MCF-7 cells. Our results suggest a possible
      therapeutic strategy based on the use of resveratrol for the treatment of tumors
      that are typically unresponsive to conventional therapies because of the loss of
      normal p53 function.

PMID- 23152799
TI  - Preparation, biodistribution and neurotoxicity of liposomal cisplatin following
      convection enhanced delivery in normal and F98 glioma bearing rats.
AB  - The purpose of this study was to evaluate two novel liposomal formulations of
      cisplatin as potential therapeutic agents for treatment of the F98 rat glioma.
      The first was a commercially produced agent, LipoplatinTM, which currently is in
      a Phase III clinical trial for treatment of non-small cell lung cancer (NSCLC).
      The second, produced in our laboratory, was based on the ability of cisplatin to
      form coordination complexes with lipid cholesteryl hemisuccinate (CHEMS). The in
      vitro tumoricidal activity of the former previously has been described in detail
      by other investigators. The CHEMS liposomal formulation had a Pt loading
      efficiency of 25% and showed more potent in vitro cytotoxicity against F98 glioma
      cells than free cisplatin at 24 h. In vivo CHEMS liposomes showed high retention
      at 24 h after intracerebral (i.c.) convection enhanced delivery (CED) to F98
      glioma bearing rats. Neurotoxicologic studies were carried out in non-tumor
      bearing Fischer rats following i.c. CED of LipoplatinTM or CHEMS liposomes or
      their "hollow" counterparts. Unexpectedly, LipoplatinTM was highly neurotoxic
      when given i.c. by CED and resulted in death immediately following or within a
      few days after administration. Similarly "hollow" LipoplatinTM liposomes showed
      similar neurotoxicity indicating that this was due to the liposomes themselves
      rather than the cisplatin. This was particularly surprising since LipoplatinTM
      has been well tolerated when administered intravenously. In contrast, CHEMS
      liposomes and their "hollow" counterparts were clinically well tolerated.
      However, a variety of dose dependent neuropathologic changes from none to severe
      were seen at either 10 or 14 d following their administration. These findings
      suggest that further refinements in the design and formulation of cisplatin
      containing liposomes will be required before they can be administered i.c. by CED
      for the treatment of brain tumors and that a formulation that may be safe when
      given systemically may be highly neurotoxic when administered directly into the
      brain.

PMID- 23152800
TI  - OGDHL is a modifier of AKT-dependent signaling and NF-kappaB function.
AB  - Oxoglutarate dehydrogenase (OGDH) is the first and rate-limiting component of the
      multi-enzyme OGDH complex (OGDHC) whose malfunction is associated with neuro
      degeneration. The essential role of this complex is in the degradation of glucose
      and glutamate and the OGDHL gene (one component of OGDHC) is down-regulated by
      promoter hypermethylation in many different cancer types. These properties
      suggest a potential growth modulating role of OGDHL in cancer; however, the
      molecular mechanism through which OGDHL exerts its growth modulating function has
      not been elucidated.Here, we report that restoration of OGDHL expression in
      cervical cancer cells lacking endogenous OGDHL expression suppressed cell
      proliferation, invasion and soft agar colony formation in vitro. Knockdown of
      OGDHL expression in cervical cancer cells expressing endogenous OGDHL had the
      opposite effect. Forced expression of OGDHL increased the production of reactive
      oxygen species (ROS) leading to apoptosis through caspase 3 mediated down
      regulation of the AKT signaling cascade and decreased NF-kappaB phosphorylation.
      Conversely, silencing OGDHL stimulated the signaling pathway via increased AKT
      phosphorylation. Moreover, the addition of caspase 3 or ROS inhibitors in the
      presence of OGDHL increased AKT signaling and cervical cancer cell
      proliferation.Taken together, these data suggest that inactivation of OGDHL can
      contribute to cervical tumorigenesis via activation of the AKT signaling pathway
      and thus support it as an important anti-proliferative gene in cervical cancer.

PMID- 23152801
TI  - Inhibition of cyclooxygenase-2 reduces hypothalamic excitation in rats with
      adriamycin-induced heart failure.
AB  - BACKGROUND: The paraventricular nucleus (PVN) of the hypothalamus plays an
      important role in the progression of heart failure (HF). We investigated whether
      cyclooxygenase-2 (COX-2) inhibition in the PVN attenuates the activities of
      sympathetic nervous system (SNS) and renin-angiotensin system (RAS) in rats with
      adriamycin-induced heart failure. METHODOLOGY/PRINCIPAL FINDING: Heart failure
      was induced by intraperitoneal injection of adriamycin over a period of 2 weeks
      (cumulative dose of 15 mg/kg). On day 19, rats received intragastric
      administration daily with either COX-2 inhibitor celecoxib (CLB) or normal
      saline. Treatment with CLB reduced mortality and attenuated both myocardial
      atrophy and pulmonary congestion in HF rats. Compared with the HF rats, ventricle
      to body weight (VW/BW) and lung to body weight (LW/BW) ratios, heart rate (HR),
      left ventricular end-diastolic pressure (LVEDP), left ventricular peak systolic
      pressure (LVPSP) and maximum rate of change in left ventricular pressure (LV+/
      dp/dtmax) were improved in HF+CLB rats. Angiotensin II (ANG II), norepinephrine
      (NE), COX-2 and glutamate (Glu) in the PVN were increased in HF rats. HF rats had
      higher levels of ANG II and NE in plasma, higher level of ANG II in myocardium,
      and lower levels of ANP in plasma and myocardium. Treatment with CLB attenuated
      these HF-induced changes. HF rats had more COX-2-positive neurons and more
      corticotropin releasing hormone (CRH) positive neurons in the PVN than did
      control rats. Treatment with CLB decreased COX-2-positive neurons and CRH
      positive neurons in the PVN of HF rats. CONCLUSIONS: These results suggest that
      PVN COX-2 may be an intermediary step for PVN neuronal activation and excitatory
      neurotransmitter release, which further contributes to sympathoexcitation and RAS
      activation in adriamycin-induced heart failure. Treatment with COX-2 inhibitor
      attenuates sympathoexcitation and RAS activation in adriamycin-induced heart
      failure.

PMID- 23152802
TI  - Activation of methanogenesis by cadmium in the marine archaeon Methanosarcina
      acetivorans.
AB  - Methanosarcina acetivorans was cultured in the presence of CdCl(2) to determine
      the metal effect on cell growth and biogas production. With methanol as
      substrate, cell growth and methane synthesis were not altered by cadmium, whereas
      with acetate, cadmium slightly increased both, growth and methane rate synthesis.
      In cultures metabolically active, incubations for short-term (minutes) with 10 uM
      total cadmium increased the methanogenesis rate by 6 and 9 folds in methanol- and
      acetate-grown cells, respectively. Cobalt and zinc but not copper or iron also
      activated the methane production rate. Methanogenic carbonic anhydrase and
      acetate kinase were directly activated by cadmium. Indeed, cells cultured in 100
      uM total cadmium removed 41-69% of the heavy metal from the culture and
      accumulated 231-539 nmol Cd/mg cell protein. This is the first report showing
      that (i) Cd(2+) has an activating effect on methanogenesis, a biotechnological
      relevant process in the bio-fuels field; and (ii) a methanogenic archaea is able
      to remove a heavy metal from aquatic environments.

PMID- 23152804
TI  - Association of LIN28B with adult adiposity-related traits in females.
AB  - CONTEXT: Pubertal timing is under strong genetic control and its early onset
      associates with several adverse health outcomes in adulthood, including obesity,
      type 2 diabetes and cardiovascular disease. Recent data indicate strong
      association between pubertal timing and genetic variants near LIN28B, but it is
      currently unknown whether the gene contributes to the association between puberty
      and adult disease. OBJECTIVE: To elucidate the putative genetic link between
      early puberty and adult disease risk, we examined the association of two genetic
      variants near LIN28B with adult body size and metabolic profiles in randomly
      ascertained adult Finnish males and females. METHODS: Two single nucleotide
      polymorphisms (SNPs), rs7759938, the lead SNP previously associated with pubertal
      timing and height, and rs314279, previously also associated with menarcheal age
      but only partially correlated with rs7759938 (r(2) = 0.30), were genotyped in
      26,636 study subjects participating in the Finnish population survey FINRISK.
      Marker associations with adult height, weight, body mass index (BMI), hip and
      waist circumference, blood glucose, serum insulin and lipid/lipoprotein levels
      were determined by linear regression analyses. RESULTS: Both rs7759938 and
      rs314279 associated with adult height in both sexes (p = 2*10(-6) and p = 0.001).
      Furthermore, rs314279 associated with increased weight in females (p = 0.001).
      Conditioned analyses including both SNPs in the regression model verified that
      rs314279 independently associates with adult female weight, BMI and hip
      circumference (p<0.005). Neither SNP associated with glucose, lipid, or
      lipoprotein levels. CONCLUSION: Genetic variants near the puberty-associated gene
      LIN28B associate with adult weight and body shape in females, suggesting that the
      gene may tag molecular pathways influencing adult adiposity-related traits.

PMID- 23152803
TI  - HIV-1 tat promotes integrin-mediated HIV transmission to dendritic cells by
      binding Env spikes and competes neutralization by anti-HIV antibodies.
AB  - Use of Env in HIV vaccine development has been disappointing. Here we show that,
      in the presence of a biologically active Tat subunit vaccine, a trimeric Env
      protein prevents in monkeys virus spread from the portal of entry to regional
      lymph nodes. This appears to be due to specific interactions between Tat and Env
      spikes that form a novel virus entry complex favoring R5 or X4 virus entry and
      productive infection of dendritic cells (DCs) via an integrin-mediated pathway.
      These Tat effects do not require Tat-transactivation activity and are blocked by
      anti-integrin antibodies (Abs). Productive DC infection promoted by Tat is
      associated with a highly efficient virus transmission to T cells. In the Tat/Env
      complex the cysteine-rich region of Tat engages the Env V3 loop, whereas the Tat
      RGD sequence remains free and directs the virus to integrins present on DCs. V2
      loop deletion, which unshields the CCR5 binding region of Env, increases Tat/Env
      complex stability. Of note, binding of Tat to Env abolishes neutralization of Env
      entry or infection of DCs by anti-HIV sera lacking anti-Tat Abs, which are seldom
      present in natural infection. This is reversed, and neutralization further
      enhanced, by HIV sera containing anti-Tat Abs such as those from asymptomatic or
      Tat-vaccinated patients, or by sera from the Tat/Env vaccinated monkeys. Thus,
      both anti-Tat and anti-Env Abs are required for efficient HIV neutralization.
      These data suggest that the Tat/Env interaction increases HIV acquisition and
      spreading, as a mechanism evolved by the virus to escape anti-Env neutralizing
      Abs. This may explain the low effectiveness of Env-based vaccines, which are also
      unlikely to elicit Abs against new Env epitopes exposed by the Tat/Env
      interaction. As Tat also binds Envs from different clades, new vaccine strategies
      should exploit the Tat/Env interaction for both preventative and therapeutic
      interventions.

PMID- 23152806
TI  - Protein secretion is required for pregnancy-associated plasma protein-A to
      promote lung cancer growth in vivo.
AB  - Pregnancy-associated plasma protein-A (PAPPA) has been reported to regulate the
      activity of insulin-like growth factor (IGF) signal pathway through proteolytic
      degradation of IGF binding proteins (IGFBPs) thereby increasing the local
      concentration of free IGFs available to receptors. In this study we found that
      PAPPA is secreted from two out of seven lung cancer cell lines examined. None of
      immortalized normal bronchial epithelial cells (HBE) tested secrets PAPPA. There
      is no correlation between expression level and secretion of PAPPA in these cells.
      A cell line over-expressing PAPPA accompanied with secretion shows no notable
      changes in proliferation under cell culture conditions in vitro, but displays
      significantly augmentation of tumor growth in vivo in a xenograft model. In
      contrast, a cell line over-expressing PAPPA without secretion exhibits reduction
      of tumor growth both in vitro and in vivo. Down-regulation of PAPPA expression
      and secretion by RNAi knockdown decreases tumor growth after implanted in vivo.
      The tumor promoting activity of PAPPA appears to be mediated mainly through
      augmentation of the IGF signaling pathway as indicated by notable increases in
      downstream Akt kinase phosphorylation in tumor samples. Our results indicate that
      PAPPA secretion may play an important role in lung cancer growth and progression.

PMID- 23152805
TI  - Ras GTPases modulate morphogenesis, sporulation and cellulase gene expression in
      the cellulolytic fungus Trichoderma reesei.
AB  - BACKGROUND: The model cellulolytic fungus Trichoderma reesei (teleomorph Hypocrea
      jecorina) is capable of responding to environmental cues to compete for nutrients
      in its natural saprophytic habitat despite its genome encodes fewer degradative
      enzymes. Efficient signalling pathways in perception and interpretation of
      environmental signals are indispensable in this process. Ras GTPases represent a
      kind of critical signal proteins involved in signal transduction and regulation
      of gene expression. In T. reesei the genome contains two Ras subfamily small
      GTPases TrRas1 and TrRas2 homologous to Ras1 and Ras2 from S. cerevisiae, but
      their functions remain unknown. METHODOLOGY/PRINCIPAL FINDINGS: Here, we have
      investigated the roles of GTPases TrRas1 and TrRas2 during fungal morphogenesis
      and cellulase gene expression. We show that both TrRas1 and TrRas2 play important
      roles in some cellular processes such as polarized apical growth, hyphal branch
      formation, sporulation and cAMP level adjustment, while TrRas1 is more dominant
      in these processes. Strikingly, we find that TrRas2 is involved in modulation of
      cellulase gene expression. Deletion of TrRas2 results in considerably decreased
      transcription of cellulolytic genes upon growth on cellulose. Although the strain
      carrying a constitutively activated TrRas2(G16V) allele exhibits increased
      cellulase gene transcription, the cbh1 and cbh2 expression in this mutant still
      strictly depends on cellulose, indicating TrRas2 does not directly mediate the
      transmission of the cellulose signal. In addition, our data suggest that the
      effect of TrRas2 on cellulase gene is exerted through regulation of transcript
      abundance of cellulase transcription factors such as Xyr1, but the influence is
      independent of cAMP signalling pathway. CONCLUSIONS/SIGNIFICANCE: Together, these
      findings elucidate the functions for Ras signalling of T. reesei in cellular
      morphogenesis, especially in cellulase gene expression, which contribute to
      deciphering the powerful competitive ability of plant cell wall degrading fungi
      in nature.

PMID- 23152807
TI  - Counteracting roles of AMP deaminase and AMP kinase in the development of fatty
      liver.
AB  - Fatty liver (hepatic steatosis) is associated with nucleotide turnover, loss of
      ATP and generation of adenosine monophosphate (AMP). It is well known that in
      fatty liver, activity of the AMP-activated kinase (AMPK) is reduced and that its
      stimulation can prevent hepatic steatosis by both enhancing fat oxidation and
      reducing lipogenesis. Here we show that another AMP dependent enzyme, AMPD2, has
      opposing effects on fatty acid oxidation when compared to AMPK. In human
      hepatocytres, AMPD2 activation -either by overexpression or by lowering
      intracellular phosphate levels with fructose- is associated with a significant
      reduction in AMPK activity. Likewise, silencing of AMPK spontaneously increases
      AMPD activity, demonstrating that these enzymes counter-regulate each other.
      Furthermore, we show that a downstream product of AMP metabolism through AMPD2,
      uric acid, can inhibit AMPK activity in human hepatocytes. Finally, we show that
      fructose-induced fat accumulation in hepatocytes is due to a dominant stimulation
      of AMPD2 despite stimulating AMPK. In this regard, AMPD2-deficient hepatocytes
      demonstrate a further activation of AMPK after fructose exposure in association
      with increased fatty acid oxidation, and conversely silencing AMPK enhances AMPD
      dependent fat accumulation. In vivo, we show that sucrose fed rats also develop
      fatty liver that is blocked by metformin in association with both a reduction in
      AMPD activity and an increase in AMPK activity. In summary, AMPD and AMPK are
      both important in hepatic fat accumulation and counter-regulate each other. We
      present the novel finding that uric acid inhibits AMPK kinase activity in
      fructose-fed hepatocytes thus providing new insights into the pathogenesis of
      fatty liver.

PMID- 23152809
TI  - Changes in antibody seroprevalence of seven high-risk HPV types between
      nationwide surveillance studies from 1995-96 and 2006-07 in The Netherlands.
AB  - OBJECTIVE: This study evaluates trends in antibody seroprevalences of seven high
      risk human papillomavirus (hr-HPV) serotypes (HPV16, 18, 31, 33, 45, 52, and 58)
      between the 1995-96 and 2006-07 sero-surveys among the Dutch general population
      in the pre-vaccination era. METHODS: Serum samples of men and women (0-79 years
      of age) from two cross-sectional population-based serosurveillance studies
      performed in 1995-96 (n = 3303) and 2006-07 (n = 6384) were tested for HPV
      specific antibodies in a VLP-based multiplex immunoassay. RESULTS: HPV16-specific
      antibody seroprevalence increased during adolescence and shifted to younger ages
      in the 2006-07 survey compared to the 1995-96 survey. This step-up in HPV16
      seroprevalence was most pronounced in women, while a more gradual increase was
      observed in men. Also in cohorts older than 49 years, HPV16 seroprevalence was
      higher in 2006-07 as compared to 1995-96 survey. A higher overall seroprevalence
      in individuals older than 15 years of age was found for HPV16, 18, 31 and 45 in
      2006-07 as compared to 1995-96. For HPV33, 52 and 58 seroprevalences were
      comparable over this 11-year time period. Seropositivity for one or more HPV
      types was significantly higher in 2006-07 (23.1%) than in 1995-96 (20.0%) (p =
      0.013). Multi-seropositivity increased from 7.1% in 1995-96 up to 10.2% in 2006
      07 (p<0.0001). Differences in HPV seropositivity for at least one of the seven
      HPV types between both surveys could be explained in addition to demographic
      characteristics (age, sex, urbanization degree and ethnicity), also by changes in
      sexual behaviour (marital status, age of sexual debut and ever reported an STI).
      CONCLUSION: The observed increase in particular HPV16 seroprevalence could be due
      to changes in sexual behaviour over the years, and especially in age of sexual
      debut. Seroprevalence studies provide insight into the distribution of HPV types
      and infection dynamics in the general population over time, which is important to
      assess the impact of HPV-vaccination.

PMID- 23152808
TI  - Distribution of influenza-like illness (ILI) by occupation in Washington State,
      September 2009-August 2010.
AB  - OBJECTIVES: We aim to estimate the prevalence of influenza-like illness (ILI) by
      occupation and to identify occupations associated with increased ILI prevalence.
      METHODS: Between September 2009 and August 2010, the Centers for Disease Control
      (CDC) included questions on ILI symptoms on the Behavioral Risk Factor
      Surveillance System (BRFSS). Washington State collects the occupation of all
      employed BRFSS respondents. ILI prevalence and prevalence ratios (PR) were
      calculated by occupational group. RESULTS: There were 8,758 adult, currently
      employed, non-military respondents to the Washington BRFSS during the study
      period. The ILI prevalence for all employed respondents was 6.8% (95% Confidence
      Interval (95% CI) = 6.1, 7.6). PRs indicated a lower prevalence of ILI in
      Technicians (PR = 0.4, 95% CI = 0.2, 0.9) and Truck Drivers (PR = 0.2, 95% CI =
      0.1, 0.7) and higher prevalence in Janitors and Cleaners (PR = 2.5, 95% CI = 1.3,
      4.7) and Secretaries (PR = 2.4, 95% CI = 1.1, 5.4). CONCLUSIONS: Some occupations
      appear to have higher prevalence of ILI than others. These occupational
      differences may be explained, in part, by differing levels of social contact with
      the public or contact with contaminated surfaces at work, or by other
      occupational factors such as stress or access to health care resources.

PMID- 23152810
TI  - The effects of probiotic supplementation on experimental acute pancreatitis: a
      systematic review and meta-analysis.
AB  - BACKGROUND: In February 2008, the results of the PRObiotics in PAncreatitis TRIAl
      (PROPATRIA) were published. This study investigated the use of probiotics in
      patients suffering from severe acute pancreatitis. No differences between the
      groups were found for any of the primary endpoints. However, mortality in the
      probiotics group was significantly higher than in the placebo group. This result
      was unexpected in light of the results of the animal studies referred to in the
      trial protocol. We used the methods of systematic review and meta-analysis to
      take a closer look at the relation between the animal studies on probiotics and
      pancreatitis and the PROPATRIA-trial, focussing on indications for harmful
      effects and efficacy. METHODS AND RESULTS: Both PubMed and Embase were searched
      for original articles concerning the effects of probiotics in experimental acute
      pancreatitis, yielding thirteen studies that met the inclusion criteria. Data on
      mortality, bacterial translocation and histological damage to the pancreas were
      extracted, as well as study quality indicators. Meta-analysis of the four animal
      studies published before PROPATRIA showed that probiotic supplementation did not
      diminish mortality, reduced the overall histopathological score of the pancreas
      and reduced bacterial translocation to pancreas and mesenteric lymph nodes.
      Comparable results were found when all relevant studies published so far were
      taken into account. CONCLUSIONS: A more thorough analysis of all relevant animal
      studies carried out before (and after) the publication of the study protocol of
      the PROPATRIA trial could not have predicted the harmful effects of probiotics
      found in the PROPATRIA-trial. Moreover, meta-analysis of the preclinical animal
      studies did show evidence for efficacy. It may be suggested, however, that the
      most appropriate animal experiments in relation to the design of the human trial
      have not yet been conducted, which compromises a fair comparison between the
      results of the animal studies and the PROPATRIA trial.

PMID- 23152811
TI  - A late miocene accipitrid (Aves: Accipitriformes) from Nebraska and its
      implications for the divergence of old world vultures.
AB  - BACKGROUND: Old World vultures are likely polyphyletic, representing two
      subfamilies, the Aegypiinae and Gypaetinae, and some genera of the latter may be
      of independent origin. Evidence concerning the origin, as well as the timing of
      the divergence of each subfamily and even genera of the Gypaetinae has been
      elusive. METHODOLOGY/PRINCIPAL FINDINGS: Compared with the Old World, the New
      World has an unexpectedly diverse and rich fossil component of Old World
      vultures. Here we describe a new accipitriform bird, Anchigyps voorhiesi gen. et
      sp. nov., from the Ash Hollow Formation (Upper Clarendonian, Late Miocene) of
      Nebraska. It represents a form close in morphology to the Old World vultures.
      Characteristics of its wing bones suggest it was less specialized for soaring
      than modern vultures. It was likely an opportunistic predator or scavenger having
      a grasping foot and a mandible morphologically similar to modern carrion-feeding
      birds. CONCLUSIONS/SIGNIFICANCE: The new fossil reported here is intermediate in
      morphology between the bulk of accipitrids and the Old World gypaetine vultures,
      representing a basal lineage of Accipitridae trending towards the vulturine
      habit, and of its Late Miocene age suggests the divergence of true gypaetine
      vultures, may have occurred during or slightly before the Miocene.

PMID- 23152812
TI  - AFM probing the mechanism of synergistic effects of the green tea polyphenol (-)
      epigallocatechin-3-gallate (EGCG) with cefotaxime against extended-spectrum beta
      lactamase (ESBL)-producing Escherichia coli.
AB  - BACKGROUND: Extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae
      poses serious challenges to clinicians because of its resistance to many classes
      of antibiotics. METHODS AND FINDINGS: The mechanism of synergistic activity of a
      combination of (-)-epigallocatechin-3-gallate (EGCG) and beta-lactam antibiotics
      cefotaxime was studied on Extended-spectrum beta-lactamase producing Escherichia
      coli (ESBL-EC), by visualizing the morphological alteration on the cell wall
      induced by the combination using atomic force microscopy (AFM). Cells at sub-MICs
      (sub-minimum inhibitory concentrations) of cefotaxime were initially filamentated
      but recovered to the normal shape later, whereas cells at sub-MICs of EGCG
      experienced temporal disturbance on the cell wall such as leakage and release of
      cellular debris and groove formation, but later recovered to the normal shape. In
      contrast, the combination of cefotaxime and EGCG at their respective sub-MICs
      induced permanent cellular damages as well as continuous elongation in cells and
      eventually killed them. Flow cytometry showed that intracellular oxidative stress
      levels in the cell treated with a combination of EGCG and cefotaxime at sub-MICs
      were higher than those in the cells treated with either cefotaxime or EGCG at sub
      MICs. CONCLUSIONS: These results suggest that the synergistic effect of EGCG
      between EGCG and cefotaxime against ESBL-EC is related to cooperative activity of
      exogenous and endogenous reactive oxygen species (ROS) generated by EGCG and
      cefotaxime, respectively.

PMID- 23152813
TI  - Identification of plasma lipid biomarkers for prostate cancer by lipidomics and
      bioinformatics.
AB  - BACKGROUND: Lipids have critical functions in cellular energy storage, structure
      and signaling. Many individual lipid molecules have been associated with the
      evolution of prostate cancer; however, none of them has been approved to be used
      as a biomarker. The aim of this study is to identify lipid molecules from
      hundreds plasma apparent lipid species as biomarkers for diagnosis of prostate
      cancer. METHODOLOGY/PRINCIPAL FINDINGS: Using lipidomics, lipid profiling of 390
      individual apparent lipid species was performed on 141 plasma samples from 105
      patients with prostate cancer and 36 male controls. High throughput data
      generated from lipidomics were analyzed using bioinformatic and statistical
      methods. From 390 apparent lipid species, 35 species were demonstrated to have
      potential in differentiation of prostate cancer. Within the 35 species, 12 were
      identified as individual plasma lipid biomarkers for diagnosis of prostate cancer
      with a sensitivity above 80%, specificity above 50% and accuracy above 80%. Using
      top 15 of 35 potential biomarkers together increased predictive power
      dramatically in diagnosis of prostate cancer with a sensitivity of 93.6%,
      specificity of 90.1% and accuracy of 97.3%. Principal component analysis (PCA)
      and hierarchical clustering analysis (HCA) demonstrated that patient and control
      populations were visually separated by identified lipid biomarkers. RandomForest
      and 10-fold cross validation analyses demonstrated that the identified lipid
      biomarkers were able to predict unknown populations accurately, and this was not
      influenced by patient's age and race. Three out of 13 lipid classes,
      phosphatidylethanolamine (PE), ether-linked phosphatidylethanolamine (ePE) and
      ether-linked phosphatidylcholine (ePC) could be considered as biomarkers in
      diagnosis of prostate cancer. CONCLUSIONS/SIGNIFICANCE: Using lipidomics and
      bioinformatic and statistical methods, we have identified a few out of hundreds
      plasma apparent lipid molecular species as biomarkers for diagnosis of prostate
      cancer with a high sensitivity, specificity and accuracy.

PMID- 23152814
TI  - Maternal tetanus toxoid vaccination and neonatal mortality in rural north India.
AB  - OBJECTIVES: Preventable neonatal mortality due to tetanus infection remains
      common. We aimed to examine antenatal vaccination impact in a context of
      continuing high neonatal mortality in rural northern India. METHODS AND FINDINGS:
      Using the third round of the Indian National Family Health Survey (NFHS) 2005-06,
      mortality of most recent singleton births was analysed in discrete-time logistic
      model with maternal tetanus vaccination, together with antenatal care utilisation
      and supplementation with iron and folic acid. 59% of mothers reported receiving
      antenatal care, 48% reported receiving iron and folic acid supplementation and
      68% reported receiving two or more doses of tetanus toxoid (TT) vaccination. The
      odds of all-cause neonatal death were reduced following one or more antenatal
      dose of TT with odds ratios (OR) of 0.46 (95% CI 0.26 to 0.78) after one dose and
      0.45 (95% CI 0.31 to 0.66) after two or more doses. Reported utilisation of
      antenatal care and iron-folic acid supplementation did not influence neonatal
      mortality. In the statistical model, 16% (95% CI 5% to 27%) of neonatal deaths
      could be attributed to a lack of at least two doses of TT vaccination during
      pregnancy, representing an estimated 78,632 neonatal deaths in absolute terms.
      CONCLUSIONS: Substantial gains in newborn survival could be achieved in rural
      North India through increased coverage of antenatal TT vaccination. The apparent
      substantial protective effect of a single antenatal dose of TT requires further
      study. It may reflect greater population vaccination coverage and indicates that
      health programming should prioritise universal antenatal coverage with at least
      one dose.

PMID- 23152816
TI  - Generating correlation matrices based on the boundaries of their coefficients.
AB  - Correlation coefficients among multiple variables are commonly described in the
      form of matrices. Applications of such correlation matrices can be found in many
      fields, such as finance, engineering, statistics, and medicine. This article
      proposes an efficient way to sequentially obtain the theoretical bounds of
      correlation coefficients together with an algorithm to generate n * n correlation
      matrices using any bounded random variables. Interestingly, the correlation
      matrices generated by this method using uniform random variables as an example
      produce more extreme relationships among the variables than other methods, which
      might be useful for modeling complex biological systems where rare cases are very
      important.

PMID- 23152815
TI  - Reduced hippocampal volume in healthy young ApoE4 carriers: an MRI study.
AB  - The E4 allele of the ApoE gene has consistently been shown to be related to an
      increased risk of Alzheimer's disease (AD). The E4 allele is also associated with
      functional and structural grey matter (GM) changes in healthy young, middle-aged
      and older subjects. Here, we assess volumes of deep grey matter structures of 22
      healthy younger ApoE4 carriers and 22 non-carriers (20-38 years). Volumes of the
      nucleus accumbens, amygdala, caudate nucleus, hippocampus, pallidum, putamen,
      thalamus and brain stem were calculated by FMRIB's Integrated Registration and
      Segmentation Tool (FIRST) algorithm. A significant drop in volume was found in
      the right hippocampus of ApoE4 carriers (ApoE4+) relative to non-carriers (ApoE4
      ), while there was a borderline significant decrease in the volume of the left
      hippocampus of ApoE4 carriers. The volumes of no other structures were found to
      be significantly affected by genotype. Atrophy has been found to be a sensitive
      marker of neurodegenerative changes, and our results show that within a healthy
      young population, the presence of the ApoE4+ carrier gene leads to volume
      reduction in a structure that is vitally important for memory formation. Our
      results suggest that the hippocampus may be particularly vulnerable to further
      degeneration in ApoE4 carriers as they enter middle and old age. Although volume
      reductions were noted bilaterally in the hippocampus, atrophy was more pronounced
      in the right hippocampus. This finding relates to previous work which has noted a
      compensatory increase in right hemisphere activity in ApoE4 carriers in response
      to preclinical declines in memory function. Possession of the ApoE4 allele may
      lead to greater predilection for right hemisphere atrophy even in healthy young
      subjects in their twenties.

PMID- 23152817
TI  - Information and communication technology use and economic growth.
AB  - In recent years, progress in information and communication technology (ICT) has
      caused many structural changes such as reorganizing of economics, globalization,
      and trade extension, which leads to capital flows and enhancing information
      availability. Moreover, ICT plays a significant role in development of each
      economic sector, especially during liberalization process. Growth economists
      predict that economic growth is driven by investments in ICT. However, empirical
      studies on this issue have produced mixed results, regarding to different
      research methodology and geographical configuration of the study. This paper
      examines the impact of Information and Communication Technology (ICT) use on
      economic growth using the Generalized Method of Moments (GMM) estimator within
      the framework of a dynamic panel data approach and applies it to 159 countries
      over the period 2000 to 2009. The results indicate that there is a positive
      relationship between growth rate of real GDP per capita and ICT use index (as
      measured by the number of internet users, fixed broadband internet subscribers
      and the number of mobile subscription per 100 inhabitants). We also find that the
      effect of ICT use on economic growth is higher in high income group rather than
      other groups. This implies that if these countries seek to enhance their economic
      growth, they need to implement specific policies that facilitate ICT use.

PMID- 23152818
TI  - Tracing the origin of the east-west population admixture in the Altai region
      (Central Asia).
AB  - A recent discovery of Iron Age burials (Pazyryk culture) in the Altai Mountains
      of Mongolia may shed light on the mode and tempo of the generation of the current
      genetic east-west population admixture in Central Asia. Studies on ancient
      mitochondrial DNA of this region suggest that the Altai Mountains played the role
      of a geographical barrier between West and East Eurasian lineages until the
      beginning of the Iron Age. After the 7th century BC, coinciding with Scythian
      expansion across the Eurasian steppes, a gradual influx of East Eurasian
      sequences in Western steppes is detected. However, the underlying events behind
      the genetic admixture in Altai during the Iron Age are still unresolved: 1)
      whether it was a result of migratory events (eastward firstly, westward
      secondly), or 2) whether it was a result of a local demographic expansion in a
      'contact zone' between European and East Asian people. In the present work, we
      analyzed the mitochondrial DNA lineages in human remains from Bronze and Iron Age
      burials of Mongolian Altai. Here we present support to the hypothesis that the
      gene pool of Iron Age inhabitants of Mongolian Altai was similar to that of
      western Iron Age Altaians (Russia and Kazakhstan). Thus, this people not only
      shared the same culture (Pazyryk), but also shared the same genetic east-west
      population admixture. In turn, Pazyryks appear to have a similar gene pool that
      current Altaians. Our results further show that Iron Age Altaians displayed
      mitochondrial lineages already present around Altai region before the Iron Age.
      This would provide support for a demographic expansion of local people of Altai
      instead of westward or eastward migratory events, as the demographic event behind
      the high population genetic admixture and diversity in Central Asia.

PMID- 23152819
TI  - Word boundaries affect visual attention in Chinese reading.
AB  - In two experiments, we explored attention deployment during the reading of
      Chinese words using a probe detection task. In both experiments, Chinese readers
      saw four simplified Chinese characters briefly, and then a probe was presented at
      one of the character positions. The four characters constituted either one word
      or two words of two characters each. Reaction time was shorter when the probe was
      at the character 2 position than the character 3 position in the two-word
      condition, but not in the one-word condition. In Experiment 2, there were more
      trials and the materials were more carefully controlled, and the results
      replicated that of Experiment 1. These results suggest that word boundary
      information affects attentional deployment in Chinese reading.

PMID- 23152820
TI  - Characterization of a new CAMP factor carried by an integrative and conjugative
      element in Streptococcus agalactiae and spreading in Streptococci.
AB  - Genetic exchanges between Streptococci occur frequently and contribute to their
      genome diversification. Most of sequenced streptococcal genomes carry multiple
      mobile genetic elements including Integrative and Conjugative Elements (ICEs)
      that play a major role in these horizontal gene transfers. In addition to genes
      involved in their mobility and regulation, ICEs also carry genes that can confer
      selective advantages to bacteria. Numerous elements have been described in S.
      agalactiae especially those integrated at the 3' end of a tRNA(Lys) encoding
      gene. In strain 515 of S. agalactiae, an invasive neonate human pathogen, the ICE
      (called 515_tRNA(Lys)) is functional and carries different putative virulence
      genes including one encoding a putative new CAMP factor in addition to the one
      previously described. This work demonstrated the functionality of this CAMP
      factor (CAMP factor II) in Lactococcus lactis but also in pathogenic strains of
      veterinary origin. The search for co-hemolytic factors in a collection of field
      strains revealed their presence in S. uberis, S. dysgalactiae, but also for the
      first time in S. equisimilis and S. bovis. Sequencing of these genes revealed the
      prevalence of a species-specific factor in S. uberis strains (Uberis factor) and
      the presence of a CAMP factor II encoding gene in S. bovis and S. equisimilis.
      Furthermore, most of the CAMP factor II positive strains also carried an element
      integrated in the tRNA(Lys) gene. This work thus describes a CAMP factor that is
      carried by a mobile genetic element and has spread to different streptococcal
      species.

PMID- 23152821
TI  - Modeling the role of negative cooperativity in metabolic regulation and
      homeostasis.
AB  - A significant proportion of enzymes display cooperativity in binding ligand
      molecules, and such effects have an important impact on metabolic regulation.
      This is easiest to understand in the case of positive cooperativity. Sharp
      responses to changes in metabolite concentrations can allow organisms to better
      respond to environmental changes and maintain metabolic homeostasis. However,
      despite the fact that negative cooperativity is almost as common as positive, it
      has been harder to imagine what advantages it provides. Here we use computational
      models to explore the utility of negative cooperativity in one particular
      context: that of an inhibitor binding to an enzyme. We identify several factors
      which may contribute, and show that acting together they can make negative
      cooperativity advantageous.

PMID- 23152822
TI  - Improvement of left ventricular function under cardiac resynchronization therapy
      goes along with a reduced incidence of ventricular arrhythmia.
AB  - OBJECTIVES: The beneficial effects of cardiac resynchronization therapy (CRT) are
      thought to result from favorable left ventricular (LV) reverse remodeling,
      however CRT is only successful in about 70% of patients. Whether response to CRT
      is associated with a decrease in ventricular arrhythmias (VA) is still discussed
      controversially. Therefore, we investigated the incidence of VA in CRT responders
      in comparison with non-responders. METHODS: In this nonrandomized, two-center,
      observational study patients with moderate-to-severe heart failure, LV ejection
      fraction (LVEF) <=35%, and QRS duration >120 ms undergoing CRT were included.
      After 6 months patients were classified as CRT responders or non-responders.
      Incidence of VA was compared between both groups by Kaplan-Meier analysis and Cox
      regression analysis. ROC analysis was performed to determine the aptitude of LVEF
      cut-off values to predict VA. RESULTS: In total 126 consecutive patients (64+/-11
      years; 67%male) were included, 74 were classified as responders and 52 as non
      responders. While the mean LVEF at baseline was comparable in both groups (25+/
      7% vs. 24+/-8%; P = 0.4583) only the responder group showed an improvement of
      LVEF (36+/-6% vs. 24+/-7; p<0.0001) under CRT. In total in 56 patients VA were
      observed during a mean follow-up of 28+/-14 months, with CRT responders
      experiencing fewer VA than non-responders (35% vs. 58%, p<0.0061). Secondary
      preventive CRT implantation was associated with a higher likelihood of VA. As
      determined by ROC analysis an increase of LVEF by >7% was found to be a predictor
      of a significantly lower incidence of VA (AUC = 0.606). CONCLUSIONS: Improvement
      of left ventricular function under cardiac resynchronization therapy goes along
      with a reduced incidence of ventricular arrhythmia.

PMID- 23152823
TI  - Estrogen-dependent uterine secretion of osteopontin activates blastocyst adhesion
      competence.
AB  - Embryo implantation is a highly orchestrated process that involves blastocyst
      uterine interactions. This process is confined to a defined interval during
      gestation referred to as the "window of embryo implantation receptivity". In mice
      this receptive period is controlled by ovarian estrogen and involves a
      coordination of blastocyst adhesion competence and uterine receptivity.
      Mechanisms coordinating the acquisition of blastocyst adhesion competence and
      uterine receptivity are largely unknown. Here, we show that ovarian estrogen
      indirectly regulates blastocyst adhesion competence. Acquisition of blastocyst
      adhesion competence was attributed to integrin activation (e.g. formation of
      adhesion complexes) rather than de novo integrin synthesis. Osteopontin (OPN) was
      identified as an estrogen-dependent uterine endometrial gland secretory factor
      responsible for activating blastocyst adhesion competence. Increased adhesion
      complex assembly in OPN-treated blastocysts was mediated through focal adhesion
      kinase (FAK)- and phosphatidylinositol 3-kinase (PI3K)-dependent signaling
      pathways. These findings define for the first time specific regulatory components
      of an estrogen-dependent pathway coordinating blastocyst adhesion competence and
      uterine receptivity.

PMID- 23152825
TI  - Characterization of a novel population of low-density granulocytes associated
      with disease severity in HIV-1 infection.
AB  - The mechanisms resulting in progressive immune dysfunction during the chronic
      phase of HIV infection are not fully understood. We have previously shown that
      arginase, an enzyme with potent immunosuppressive properties, is increased in HIV
      seropositive (HIV+) patients with low CD4(+) T cell counts. Here we show that the
      cells expressing arginase in peripheral blood mononuclear cells of HIV+ patients
      are low-density granulocytes (LDGs) and that whereas these cells have a similar
      morphology to normal-density granulocyte, they are phenotypically different.
      Importantly, our results reveal that increased frequencies of LDGs correlate with
      disease severity in HIV+ patients.

PMID- 23152824
TI  - High-level transient expression of ER-targeted human interleukin 6 in Nicotiana
      benthamiana.
AB  - Tobacco plants can be used to express recombinant proteins that cannot be
      produced in a soluble and active form using traditional platforms such as
      Escherichia coli. We therefore expressed the human glycoprotein interleukin 6
      (IL6) in two commercial tobacco cultivars (Nicotiana tabacum cv. Virginia and cv.
      Geudertheimer) as well as the model host N. benthamiana to compare different
      transformation strategies (stable vs. transient expression) and subcellular
      targeting (apoplast, endoplasmic reticulum (ER) and vacuole). In T(0) transgenic
      plants, the highest expression levels were achieved by ER targeting but the
      overall yields of IL6 were still low in the leaves (0.005% TSP in the ER, 0.0008%
      in the vacuole and 0.0005% in the apoplast). The apoplast variant accumulated to
      similar levels in leaves and seeds, whereas the ER-targeted variant was 1.2-fold
      more abundant in seeds and the vacuolar variant was 6-fold more abundant in
      seeds. The yields improved in subsequent generations, with the best-performing
      T(2) plants producing the ER-targeted IL6 at 0.14% TSP in both leaves and seeds.
      Transient expression of ER-targeted IL6 in leaves using the MagnICON system
      resulted in yields of up to 7% TSP in N. benthamiana, but only 1% in N. tabacum
      cv. Virginia and 0.5% in cv. Geudertheimer. Although the commercial tobacco
      cultivars produced up to threefold more biomass than N. benthamiana, this was not
      enough to compensate for the lower overall yields. The recombinant IL6 produced
      by transient and stable expression in plants was biologically active and
      presented as two alternative bands matching the corresponding native protein.

PMID- 23152826
TI  - Q fever in pregnant goats: pathogenesis and excretion of Coxiella burnetii.
AB  - Coxiella burnetii is an intracellular bacterial pathogen that causes Q fever.
      Infected pregnant goats are a major source of human infection. However, the
      tissue dissemination and excretion pathway of the pathogen in goats are still
      poorly understood. To better understand Q fever pathogenesis, we inoculated
      groups of pregnant goats via the intranasal route with a recent Dutch outbreak C.
      burnetii isolate. Tissue dissemination and excretion of the pathogen were
      followed for up to 95 days after parturition. Goats were successfully infected
      via the intranasal route. PCR and immunohistochemistry showed strong tropism of
      C. burnetii towards the placenta at two to four weeks after inoculation.
      Bacterial replication seemed to occur predominantly in the trophoblasts of the
      placenta and not in other organs of goats and kids. The amount of C. burnetii DNA
      in the organs of goats and kids increased towards parturition. After parturition
      it decreased to undetectable levels: after 81 days post-parturition in goats and
      after 28 days post-parturition in kids. Infected goats gave birth to live or dead
      kids. High numbers of C. burnetii were excreted during abortion, but also during
      parturition of liveborn kids. C. burnetii was not detected in faeces or vaginal
      mucus before parturition. Our results are the first to demonstrate that pregnant
      goats can be infected via the intranasal route. C. burnetii has a strong tropism
      for the trophoblasts of the placenta and is not excreted before parturition;
      pathogen excretion occurs during birth of dead as well as healthy animals.
      Besides abortions, normal deliveries in C. burnetii-infected goats should be
      considered as a major zoonotic risk for Q fever in humans.

PMID- 23152827
TI  - Prevention of acute kidney injury by tauroursodeoxycholic acid in rat and cell
      culture models.
AB  - BACKGROUND: Acute kidney injury (AKI) has grave short- and long-term
      consequences. Often the onset of AKI is predictable, such as following surgery
      that compromises blood flow to the kidney. Even in such situations, present
      therapies cannot prevent AKI. As apoptosis is a major form of cell death
      following AKI, we determined the efficacy and mechanisms of action of
      tauroursodeoxycholic acid (TUDCA), a molecule with potent anti-apoptotic and pro
      survival properties, in prevention of AKI in rat and cell culture models. TUDCA
      is particularly attractive from a translational standpoint, as it has a proven
      safety record in animals and humans. METHODOLOGY/PRINCIPAL FINDINGS: We chose an
      ischemia-reperfusion model in rats to simulate AKI in native kidneys, and a human
      kidney cell culture model to simulate AKI associated with cryopreservation in
      transplanted kidneys. TUDCA significantly ameliorated AKI in the test models due
      to inhibition of the mitochondrial pathway of apoptosis and upregulation of
      survival pathways. CONCLUSIONS: This study sets the stage for testing TUDCA in
      future clinical trials for prevention of AKI, an area that needs urgent attention
      due to lack of effective therapies.

PMID- 23152828
TI  - Contrast-based fully automatic segmentation of white matter hyperintensities:
      method and validation.
AB  - White matter hyperintensities (WMH) on T2 or FLAIR sequences have been commonly
      observed on MR images of elderly people. They have been associated with various
      disorders and have been shown to be a strong risk factor for stroke and dementia.
      WMH studies usually required visual evaluation of WMH load or time-consuming
      manual delineation. This paper introduced WHASA (White matter Hyperintensities
      Automated Segmentation Algorithm), a new method for automatically segmenting WMH
      from FLAIR and T1 images in multicentre studies. Contrary to previous approaches
      that were based on intensities, this method relied on contrast: non linear
      diffusion filtering alternated with watershed segmentation to obtain piecewise
      constant images with increased contrast between WMH and surroundings tissues. WMH
      were then selected based on subject dependant automatically computed threshold
      and anatomical information. WHASA was evaluated on 67 patients from two studies,
      acquired on six different MRI scanners and displaying a wide range of lesion
      load. Accuracy of the segmentation was assessed through volume and spatial
      agreement measures with respect to manual segmentation; an intraclass correlation
      coefficient (ICC) of 0.96 and a mean similarity index (SI) of 0.72 were obtained.
      WHASA was compared to four other approaches: Freesurfer and a thresholding
      approach as unsupervised methods; k-nearest neighbours (kNN) and support vector
      machines (SVM) as supervised ones. For these latter, influence of the training
      set was also investigated. WHASA clearly outperformed both unsupervised methods,
      while performing at least as good as supervised approaches (ICC range: 0.87-0.91
      for kNN; 0.89-0.94 for SVM. Mean SI: 0.63-0.71 for kNN, 0.67-0.72 for SVM), and
      did not need any training set.

PMID- 23152829
TI  - Heart failure induces significant changes in nuclear pore complex of human
      cardiomyocytes.
AB  - AIMS: The objectives of this study were to analyse the effect of heart failure
      (HF) on several proteins of nuclear pore complex (NPC) and their relationship
      with the human ventricular function. METHODS AND RESULTS: A total of 88 human
      heart samples from ischemic (ICM, n = 52) and dilated (DCM, n = 36) patients
      undergoing heart transplant and control donors (CNT, n = 9) were analyzed by
      Western blot. Subcellular distribution of nucleoporins was analysed by
      fluorescence and immunocytochemistry. When we compared protein levels according
      to etiology, ICM showed significant higher levels of NDC1 (65%, p<0.0001), Nup160
      (88%, p<0.0001) and Nup153 (137%, p = 0.004) than those of the CNT levels.
      Furthermore, DCM group showed significant differences for NDC1 (41%, p<0.0001),
      Nup160 (65%, p<0.0001), Nup153 (155%, p = 0.006) and Nup93 (88%, p<0.0001)
      compared with CNT. However, Nup155 and translocated promoter region (TPR) did not
      show significant differences in their levels in any etiology. Regarding the
      distribution of these proteins in cell nucleus, only NDC1 showed differences in
      HF. In addition, in the pathological group we obtained good relationship between
      the ventricular function parameters (LVEDD and LVESD) and Nup160 (r = -0382, p =
      0.004; r = -0.290, p = 0.033; respectively). CONCLUSIONS: This study shows
      alterations in specific proteins (NDC1, Nup160, Nup153 and Nup93) that compose
      NPC in ischaemic and dilated human heart. These changes, related to ventricular
      function, could be accompanied by alterations in the nucleocytoplasmic transport.
      Therefore, our findings may be the basis for a new approach to HF management.

PMID- 23152830
TI  - Across-shelf transport of bivalve larvae: can the interface between a coastal
      current and inshore waters act as an ecological barrier to larval dispersal?
AB  - Using an integrated physical and biological approach, we examined across-shelf
      advection and exchange and the associated transport of bivalve larvae in the
      presence of a strong coastal current separated from the coast by a stratified
      inshore environment. We tested the hypothesis that the interface of the coastal
      current and inshore waters can act as an ecological barrier to across-shelf
      transport of larvae but can be overcome by wind- or tidally-induced transport.
      Our study region in the Gulf of Maine encompasses a coastal current that diverges
      from the coast as it moves downshelf. The region inshore of this current is home
      to several species that exhibit limited recruitment in spite of extensive upshelf
      larval sources. Analysis of surface water temperatures and wind velocities
      revealed episodic decreases in temperature along the coast correlated with
      alongshelf (but not upwelling) winds, indicating wind-forced onshore movement of
      the cold coastal current. Such wind-driven onshore migrations are more common
      along the northern portion of the study region where the coastal current is near
      the coast, tidal currents are strong, and wind directions are more conducive to
      onshore migration, but rarer further south where the interface between inshore
      waters and the coastal current is further offshore and suitable wind events are
      less common. The distribution of bivalve larvae was consistent with the physical
      measurements. There was little across-shelf variation in larval abundance where
      the current abuts the coast, indicating strong across-shelf exchange of larvae,
      but strong across-shelf variation in larval density where the stratified inshore
      waters separate the current from the coast, indicating weak across-shelf
      transport of larvae. Our results suggest that the interface between the coastal
      current and inshore waters may constitute a major ecological barrier to larval
      dispersal in the southern part of the region that may only be overcome by rare,
      strong wind-forced events.

PMID- 23152831
TI  - Comparing linkage designs based on land facets to linkage designs based on focal
      species.
AB  - Least-cost modeling for focal species is the most widely used method for
      designing conservation corridors and linkages. However, these designs depend on
      today's land covers, which will be altered by climate change. We recently
      proposed an alternative approach based on land facets (recurring landscape units
      of relatively uniform topography and soils). The rationale is that corridors with
      high continuity of individual land facets will facilitate movement of species
      associated with each facet today and in the future. Conservation practitioners
      might like to know whether a linkage design based on land facets is likely to
      provide continuity of modeled breeding habitat for species needing connectivity
      today, and whether a linkage for focal species provides continuity and
      interspersion of land facets. To address these questions, we compared linkages
      designed for focal species and land facets in three landscapes in Arizona, USA.
      We used two variables to measure linkage utility, namely distances between
      patches of modeled breeding habitat for 5-16 focal species in each linkage, and
      resistance profiles for focal species and land facets between patches connected
      by the linkage. Compared to focal species designs, linkage designs based on land
      facets provided as much or more modeled habitat connectivity for 25 of 28 species
      landscape combinations, failing only for the three species with the most narrowly
      distributed habitat. Compared to land facets designs, focal species linkages
      provided lower connectivity for about half the land facets in two landscapes. In
      areas where a focal species approach to linkage design is not possible, our
      results suggest that conservation practitioners may be able to implement a land
      facets approach with some confidence that the linkage design would serve most
      potential focal species. In areas where focal species designs are possible, we
      recommend using the land facet approach to complement, rather than replace, focal
      species approaches.

PMID- 23152832
TI  - Comparative stress levels among residents in three Chinese provincial capitals,
      2001 and 2008.
AB  - OBJECTIVES: To compare stress levels among residents in large Chinese cities
      between 2001 and 2008. METHODS: Survey data were collected in three mainland
      Chinese capital cities in two waves, in 2001 and 2008, respectively. Participants
      were recruited through a multi-stage stratified sampling process. Stress was
      assessed using the Perceived Stress Scale, Chinese version (CPSS). Descriptive
      methods were used to estimate mean stress levels and associated 95% confidence
      intervals. Estimates were adjusted by post-stratification weights. RESULTS:
      Indicating stable stress levels, respective adjusted mean stress scores for the
      combined samples of study participants were 23.90 (95%CI: 23.68-24.12) in 2001
      and 23.69 (95%CI: 23.38-24.01) in 2008. A lower stress level in 2008 than in 2001
      manifested among residents who were under 25 years of age; female; with a college
      or higher level education; divorced, widowed, or separated; members of the
      managerial and clerical group; students or army personnel; or with an annual
      income of at least 30,000 RMB. CONCLUSION: The overall stress level did not
      change among the combined sample of residents in the three Chinese study cities
      between 2001 and 2008. However, levels remained high and varied across social
      strata, and may have reflected a national trend among urban residents. Findings
      indicate a need for a new health policy, and call for the design and
      implementation of evidence-based interventions that target the highest-risk
      groups.

PMID- 23152833
TI  - Simultaneous detection and differentiation of human papillomavirus genotypes 6,
      11, 16 and 18 by AllGlo quadruplex quantitative PCR.
AB  - BACKGROUND: Human papillomaviruses (HPV) are classified into high-risk HPV and
      low-risk HPV. The most common high-risk HPV types in cervical cancer are HPV 16
      and 18, and the most common low-risk types causing genital warts are HPV 6 and
      HPV 11. In this study, applying novel AllGlo fluorescent probes, we established a
      quadruplex quantitative PCR method to simultaneously detect and differentiate HPV
      6, 11, 16 and 18 in a single tube. METHODS: The specificity, the sensitivity, the
      detection limit, the reproducibility and the standard curve of this method were
      examined. Finally, clinical samples that had been tested previously by TaqMan PCR
      and HPV GenoArray (GA) test were used to verify the accuracy and sensitivity of
      the method. RESULTS: The assay has a sensitivity of 10(1) to 10(2) copies/test
      and a linear detection range from 10(1) to 10(8) copies/test. The mean
      amplification efficiencies for HPV 6, 11, 16, and 18 were 0.97, 1.10, 0.93 and
      1.20, respectively, and the mean correlation coefficient (r(2)) of each standard
      curve was above 0.99 for plasmid templates ranging from 10(3) to 10(7)
      copies/test. There was 100% agreement between the AllGlo quadruplex quantitative
      PCR, HPV GA test and TaqMan uniplex qPCR methods. CONCLUSIONS: AllGlo quadruplex
      quantitative PCR in a single tube has the advantages of relatively high
      throughput, good reproducibility, high sensitivity, high specificity, and a wide
      linear range of detection. The convenient single tube format makes this assay a
      powerful tool for the studies of mixed infections by multiple pathogens, viral
      typing and viral load quantification.

PMID- 23152834
TI  - Segmentation and visual analysis of whole-body mouse skeleton microSPECT.
AB  - Whole-body SPECT small animal imaging is used to study cancer, and plays an
      important role in the development of new drugs. Comparing and exploring whole
      body datasets can be a difficult and time-consuming task due to the inherent
      heterogeneity of the data (high volume/throughput, multi-modality, postural and
      positioning variability). The goal of this study was to provide a method to align
      and compare side-by-side multiple whole-body skeleton SPECT datasets in a common
      reference, thus eliminating acquisition variability that exists between the
      subjects in cross-sectional and multi-modal studies. Six whole-body SPECT/CT
      datasets of BALB/c mice injected with bone targeting tracers (99m)Tc-methylene
      diphosphonate ((99m)Tc-MDP) and (99m)Tc-hydroxymethane diphosphonate ((99m)Tc
      HDP) were used to evaluate the proposed method. An articulated version of the
      MOBY whole-body mouse atlas was used as a common reference. Its individual bones
      were registered one-by-one to the skeleton extracted from the acquired SPECT data
      following an anatomical hierarchical tree. Sequential registration was used while
      constraining the local degrees of freedom (DoFs) of each bone in accordance to
      the type of joint and its range of motion. The Articulated Planar Reformation
      (APR) algorithm was applied to the segmented data for side-by-side change
      visualization and comparison of data. To quantitatively evaluate the proposed
      algorithm, bone segmentations of extracted skeletons from the correspondent CT
      datasets were used. Euclidean point to surface distances between each dataset and
      the MOBY atlas were calculated. The obtained results indicate that after
      registration, the mean Euclidean distance decreased from 11.5+/-12.1 to 2.6+/-2.1
      voxels. The proposed approach yielded satisfactory segmentation results with
      minimal user intervention. It proved to be robust for "incomplete" data (large
      chunks of skeleton missing) and for an intuitive exploration and comparison of
      multi-modal SPECT/CT cross-sectional mouse data.

PMID- 23152835
TI  - Adult pancreas side population cells expand after beta cell injury and are a
      source of insulin-secreting cells.
AB  - Pancreas stem cells are a potential source of insulin-producing beta cells for
      the therapy of diabetes. In adult tissues the 'side population' (SP) of cells
      that effluxes the DNA binding dye Hoechst 33342 through ATP-binding cassette
      transporters has stem cell properties. We hypothesised therefore that the SP
      would expand in response to beta cell injury and give rise to functional beta
      cells. SP cells were flow sorted from dissociated pancreas cells of adult mice,
      analysed for phenotype and cultured with growth promoting and differentiation
      factors before analysis for hormone expression and glucose-stimulated insulin
      secretion. SP cell number and colony forming potential (CFP) increased
      significantly in models of type diabetes, and after partial pancreatectomy, in
      the absence of hyperglycaemia. SP cells, ~1% of total pancreas cells at 1 week of
      age, were enriched >10-fold for CFP compared to non-SP cells. Freshly isolated SP
      cells contained no insulin protein or RNA but expressed the homeobox
      transcription factor Pdx1 required for pancreas development and beta cell
      function. Pdx1, along with surface expression of CD326 (Ep-Cam), was a marker of
      the colony forming and proliferation potential of SP cells. In serum-free medium
      with defined factors, SP cells proliferated and differentiated into islet hormone
      expressing cells that secreted insulin in response to glucose. Insulin expression
      was maintained when tissue was transplanted within vascularised chambers into
      diabetic mice. SP cells in the adult pancreas expand in response to beta cell
      injury and are a source of beta cell progenitors with potential for the treatment
      of diabetes.

PMID- 23152836
TI  - Contrasting effects of climate change on rabbit populations through reproduction.
AB  - BACKGROUND: Climate change is affecting many physical and biological processes
      worldwide. Anticipating its effects at the level of populations and species is
      imperative, especially for organisms of conservation or management concern.
      Previous studies have focused on estimating future species distributions and
      extinction probabilities directly from current climatic conditions within their
      geographical ranges. However, relationships between climate and population
      parameters may be so complex that to make these high-level predictions we need
      first to understand the underlying biological processes driving population size,
      as well as their individual response to climatic alterations. Therefore, the
      objective of this study is to investigate the influence that climate change may
      have on species population dynamics through altering breeding season.
      METHODOLOGY/PRINCIPAL FINDINGS: We used a mechanistic model based on drivers of
      rabbit reproductive physiology together with demographic simulations to show how
      future climate-driven changes in breeding season result in contrasting rabbit
      population trends across Europe. In the Iberian Peninsula, where rabbits are a
      native species of high ecological and economic value, breeding seasons will
      shorten and become more variable leading to population declines, higher
      extinction risk, and lower resilience to perturbations. Whereas towards north
      eastern countries, rabbit numbers are expected to increase through longer and
      more stable reproductive periods, which augment the probability of new rabbit
      invasions in those areas. CONCLUSIONS/SIGNIFICANCE: Our study reveals the type of
      mechanisms through which climate will cause alterations at the species level and
      emphasizes the need to focus on them in order to better foresee large-scale
      complex population trends. This is especially important in species like the
      European rabbit whose future responses may aggravate even further its dual
      keystone/pest problematic. Moreover, this approach allows us to predict not only
      distribution shifts but also future population status and growth, and to identify
      the demographic parameters on which to focus to mitigate global change effects.

PMID- 23152837
TI  - Effect of dicycloplatin, a novel platinum chemotherapeutical drug, on inhibiting
      cell growth and inducing cell apoptosis.
AB  - Dicycloplatin, a new supramolecular platinum-based antitumor drug, has been
      approved by the State Food and Administration (SFDA) of China. In this study, we
      investigated the anticancer activity of dicycloplatin in cancer cells and
      signaling pathways involved in dicycloplatin-induced apoptosis. Dicycloplatin
      inhibited the proliferation of cancer cells and increased the percentage of
      apoptosis in a concentration-dependent manner. Besides, some apoptosis related
      events were observed after treatment with dicycloplatin, including increase of
      reactive oxygen species (ROS), collapse of mitochondrial membrane potential
      (Deltapsim), release of cytochrome c from the mitochondria to the cytosol,
      upregulation of p53, which were accompanied by activation of caspase-9, caspase
      3, caspase-8, and poly (ADP-ribose) polymerase cleavage in a concentration
      dependent manner. The role of apoptosis in dicycloplatin-mediated cell death was
      further confirmed by the concomitant treatment with caspase-8 or caspase-9
      inhibitors, which inhibited apoptosis and PARP cleavage. Intracellular
      glutathione (GSH) was also found to inhibit the cytotoxic effect of
      dicycloplatin. In conclusion, these findings suggest that dicycloplatin induces
      apoptosis through ROS stress-mediated death receptor pathway and mitochondrial
      pathway which is similar to carboplatin.

PMID- 23152838
TI  - Statistical object data analysis of taxonomic trees from human microbiome data.
AB  - Human microbiome research characterizes the microbial content of samples from
      human habitats to learn how interactions between bacteria and their host might
      impact human health. In this work a novel parametric statistical inference method
      based on object-oriented data analysis (OODA) for analyzing HMP data is proposed.
      OODA is an emerging area of statistical inference where the goal is to apply
      statistical methods to objects such as functions, images, and graphs or trees.
      The data objects that pertain to this work are taxonomic trees of bacteria built
      from analysis of 16S rRNA gene sequences (e.g. using RDP); there is one such
      object for each biological sample analyzed. Our goal is to model and formally
      compare a set of trees. The contribution of our work is threefold: first, a
      weighted tree structure to analyze RDP data is introduced; second, using a
      probability measure to model a set of taxonomic trees, we introduce an
      approximate MLE procedure for estimating model parameters and we derive LRT
      statistics for comparing the distributions of two metagenomic populations; and
      third the Jumpstart HMP data is analyzed using the proposed model providing novel
      insights and future directions of analysis.

PMID- 23152839
TI  - Randomized, placebo-controlled trial of mipomersen in patients with severe
      hypercholesterolemia receiving maximally tolerated lipid-lowering therapy.
AB  - OBJECTIVES: Mipomersen, an antisense oligonucleotide targeting apolipoprotein B
      synthesis, significantly reduces LDL-C and other atherogenic lipoproteins in
      familial hypercholesterolemia when added to ongoing maximally tolerated lipid
      lowering therapy. Safety and efficacy of mipomersen in patients with severe
      hypercholesterolemia was evaluated. METHODS AND RESULTS: Randomized, double
      blind, placebo-controlled, multicenter trial. Patients (n  = 58) were >=18 years
      with LDL-C >=7.8 mmol/L or LDL-C >=5.1 mmol/L plus CHD disease, on maximally
      tolerated lipid-lowering therapy that excluded apheresis. Weekly subcutaneous
      injections of mipomersen 200 mg (n  = 39) or placebo (n  = 19) were added to
      lipid-lowering therapy for 26 weeks. MAIN OUTCOME: percent reduction in LDL-C
      from baseline to 2 weeks after the last dose of treatment. Mipomersen (n = 27)
      reduced LDL-C by 36%, from a baseline of 7.2 mmol/L, for a mean absolute
      reduction of 2.6 mmol/L. Conversely, mean LDL-C increased 13% in placebo (n = 18)
      from a baseline of 6.5 mmol/L (mipomersen vs placebo p<0.001). Mipomersen
      produced statistically significant (p<0.001) reductions in apolipoprotein B and
      lipoprotein(a), with no change in high-density lipoprotein cholesterol. Mild-to
      moderate injection site reactions were the most frequently reported adverse
      events with mipomersen. Mild-to-moderate flu-like symptoms were reported more
      often with mipomersen. Alanine transaminase increase, aspartate transaminase
      increase, and hepatic steatosis occurred in 21%, 13% and 13% of mipomersen
      treated patients, respectively. Adverse events by category for the placebo and
      mipomersen groups respectively were: total adverse events, 16(84.2%), 39(100%);
      serious adverse events, 0(0%), 6(15.4%); discontinuations due to adverse events,
      1(5.3%), 8(20.5%) and cardiac adverse events, 1(5.3%), 5(12.8%). CONCLUSION:
      Mipomersen significantly reduced LDL-C, apolipoprotein B, total cholesterol and
      non-HDL-cholesterol, and lipoprotein(a). Mounting evidence suggests it may be a
      potential pharmacologic option for lowering LDL-C in patients with severe
      hypercholesterolemia not adequately controlled using existing therapies. Future
      studies will explore alternative dosing schedules aimed at minimizing side
      effects. TRIAL REGISTRATION: ClinicalTrials.gov NCT00794664.

PMID- 23152840
TI  - Sequential Notch signalling at the boundary of fringe expressing and non
      expressing cells.
AB  - Wing development in Drosophila requires the activation of Wingless (Wg) in a
      small stripe along the boundary of Fringe (Fng) expressing and non-expressing
      cells (FB), which coincides with the dorso-ventral (D/V) boundary of the wing
      imaginal disc. The expression of Wg is induced by interactions between dorsal and
      ventral cells mediated by the Notch signalling pathway. It appears that mutual
      signalling from dorsal to ventral and ventral to dorsal cells by the Notch
      ligands Serrate (Ser) and Delta (Dl) respectively establishes a symmetric domain
      of Wg that straddles the D/V boundary. The directional signalling of these
      ligands requires the modification of Notch in dorsal cells by the
      glycosyltransferase Fng and is based on the restricted expression of the ligands
      with Ser expression to the dorsal and that of Dl to the ventral side of the wing
      anlage. In order to further investigate the mechanism of Notch signalling at the
      FB, we analysed the function of Fng, Ser and Dl during wing development at an
      ectopic FB and at the D/V boundary. We find that Notch signalling is initiated in
      an asymmetric fashion on only one side of the FB. During this initial asymmetric
      phase, only one ligand is required, with Ser initiating Notch-signalling at the
      D/V and Dl at the ectopic FB. Furthermore, our analysis suggests that Fng has
      also a positive effect on Ser signalling. Because of these additional properties,
      differential expression of the ligands, which has been a prerequisite to restrict
      Notch activation to the FB in the current model, is not required to restrict
      Notch signalling to the FB.

PMID- 23152841
TI  - Using digital RNA counting and flow cytometry to compare mRNA with protein
      expression in acute leukemias.
AB  - BACKGROUND: The diagnosis of malignant hematologic diseases has become
      increasingly complex during the last decade. It is based on the interpretation of
      results from different laboratory analyses, which range from microscopy to gene
      expression profiling. Recently, a method for the analysis of RNA phenotypes has
      been developed, the nCounter technology (Nanostring(r) Technologies), which
      allows for simultaneous quantification of hundreds of RNA molecules in biological
      samples. We evaluated this technique in a Swiss multi-center study on eighty-six
      samples from acute leukemia patients. METHODS: mRNA and protein profiles were
      established for normal peripheral blood and bone marrow samples. Signal
      intensities of the various tested antigens with surface expression were similar
      to those found in previously performed Affymetrix microarray analyses. Acute
      leukemia samples were analyzed for a set of twenty-two validated antigens and the
      Pearson Correlation Coefficient for nCounter and flow cytometry results was
      calculated. RESULTS: Highly significant values between 0.40 and 0.97 were found
      for the twenty-two antigens tested. A second correlation analysis performed on a
      per sample basis resulted in concordant results between flow cytometry and
      nCounter in 44-100% of the antigens tested (mean = 76%), depending on the number
      of blasts present in a sample, the homogeneity of the blast population, and the
      type of leukemia (AML or ALL). CONCLUSIONS: The nCounter technology allows for
      fast and easy depiction of a mRNA profile from hematologic samples. This
      technology has the potential to become a valuable tool for the diagnosis of acute
      leukemias, in addition to multi-color flow cytometry.

PMID- 23152842
TI  - Extensive pollen flow but few pollen donors and high reproductive variance in an
      extremely fragmented landscape.
AB  - Analysing pollen movement is a key to understanding the reproductive system of
      plant species and how it is influenced by the spatial distribution of potential
      mating partners in fragmented populations. Here we infer parameters related to
      levels of pollen movement and diversity of the effective pollen cloud for the
      wind-pollinated shrub Pistacia lentiscus across a highly disturbed landscape
      using microsatellite loci. Paternity analysis and the indirect KinDist and Mixed
      Effect Mating models were used to assess mating patterns, the pollen dispersal
      kernel, the effective number of males (N(ep)) and their relative individual
      fertility, as well as the existence of fine-scale spatial genetic structure in
      adult plants. All methods showed extensive pollen movement, with high rates of
      pollen flow from outside the study site (up to 73-93%), fat-tailed dispersal
      kernels and large average pollination distances (delta = 229-412 m). However,
      they also agreed in detecting very few pollen donors (N(ep) = 4.3-10.2) and a
      large variance in their reproductive success: 70% of males did not sire any
      offspring among the studied female plants and 5.5% of males were responsible for
      50% of pollinations. Although we did not find reduced levels of genetic
      diversity, the adult population showed high levels of biparental inbreeding (14%)
      and strong spatial genetic structure (S(p) = 0.012), probably due to restricted
      seed dispersal and scarce safe sites for recruitment. Overall, limited seed
      dispersal and the scarcity of successful pollen donors can be contributing to
      generate local pedigrees and to increase inbreeding, the prelude of genetic
      impoverishment.

PMID- 23152843
TI  - Metabolic labeling of Caenorhabditis elegans primary embryonic cells with azido
      sugars as a tool for glycoprotein discovery.
AB  - Glycobiology research with Caenorhabditis elegans (C. elegans) has benefitted
      from the numerous genetic and cell biology tools available in this system.
      However, the lack of a cell line and the relative inaccessibility of C. elegans
      somatic cells in vivo have limited the biochemical approaches available in this
      model. Here we report that C. elegans primary embryonic cells in culture
      incorporate azido-sugar analogs of N-acetylgalactosamine (GalNAc) and N
      acetylglucosamine (GlcNAc), and that the labeled glycoproteins can be analyzed by
      mass spectrometry. By using this metabolic labeling approach, we have identified
      a set of novel C. elegans glycoprotein candidates, which include several
      mitochondrially-annotated proteins. This observation was unexpected given that
      mitochondrial glycoproteins have only rarely been reported, and it suggests that
      glycosylation of mitochondrially-annotated proteins might occur more frequently
      than previously thought. Using independent experimental strategies, we validated
      a subset of our glycoprotein candidates. These include a mitochondrial, atypical
      glycoprotein (ATP synthase alpha-subunit), a predicted glycoprotein (aspartyl
      protease, ASP-4), and a protein family with established glycosylation in other
      species (actin). Additionally, we observed a glycosylated isoform of ATP synthase
      alpha-subunit in bovine heart tissue and a primate cell line (COS-7). Overall,
      our finding that C. elegans primary embryonic cells are amenable to metabolic
      labeling demonstrates that biochemical studies in C. elegans are feasible, which
      opens the door to labeling C. elegans cells with other radioactive or azido
      substrates and should enable the identification of additional post
      translationally modified targets and analysis of the genes required for their
      modification using C. elegans mutant libraries.

PMID- 23152844
TI  - IL-12p40 deficiency leads to uncontrolled Trypanosoma cruzi dissemination in the
      spinal cord resulting in neuronal death and motor dysfunction.
AB  - Chagas' disease is a protozoosis caused by Trypanosoma cruzi that frequently
      shows severe chronic clinical complications of the heart or digestive system.
      Neurological disorders due to T. cruzi infection are also described in children
      and immunosuppressed hosts. We have previously reported that IL-12p40 knockout
      (KO) mice infected with the T. cruzi strain Sylvio X10/4 develop spinal cord
      neurodegenerative disease. Here, we further characterized neuropathology,
      parasite burden and inflammatory component associated to the fatal neurological
      disorder occurring in this mouse model. Forelimb paralysis in infected IL-12p40KO
      mice was associated with 60% (p<0.05) decrease in spinal cord neuronal density,
      glutamate accumulation (153%, p<0.05) and strong demyelization in lesion areas,
      mostly in those showing heavy protein nitrosylation, all denoting a neurotoxic
      degenerative profile. Quantification of T. cruzi 18S rRNA showed that parasite
      burden was controlled in the spinal cord of WT mice, decreasing from the fifth
      week after infection, but progressive parasite dissemination was observed in IL
      12p40KO cords concurrent with significant accumulation of the astrocytic marker
      GFAP (317.0%, p<0.01) and 8-fold increase in macrophages/microglia (p<0.01),
      36.3% (p<0.01) of which were infected. Similarly, mRNA levels for CD3, TNF-alpha,
      IFN-gamma, iNOS, IL-10 and arginase I declined in WT spinal cords about the
      fourth or fifth week after infection, but kept increasing in IL-12p40KO mice.
      Interestingly, compared to WT tissue, lower mRNA levels for IFN-gamma were
      observed in the IL-12p40KO spinal cords up to the fourth week of infection.
      Together the data suggest that impairments of parasite clearance mechanisms in IL
      12p40KO mice elicit prolonged spinal cord inflammation that in turn leads to
      irreversible neurodegenerative lesions.

PMID- 23152845
TI  - The relationship between species richness and evenness in plant communities along
      a successional gradient: a study from sub-alpine meadows of the Eastern Qinghai
      Tibetan Plateau, China.
AB  - The relationship between species richness and evenness across communities remains
      an unsettled issue in ecology from both theoretical and empirical perspectives.
      As a result, we do not know the mechanisms that could generate a relationship
      between species richness and evenness, and how this responds to spatial scale.
      Here we examine the relationship between species richness(S) and evenness
      (Pielou's J' evenness) using a chronosequence of successional sub-alpine meadow
      communities in the eastern Qinghai-Tibetan Plateau. These meadows range from
      natural community (never farmed), to those that have been protected from
      agricultural exploitation for periods ranging from 1 to 10 years. A total of 30
      sampling quadrats with size of 0.5 m*0.5 m were laid out along two transects at
      each meadow. Using correlation analyses we found a consistent negative
      correlation between S and J' in these communities along the successional gradient
      at the sampling scale of 0.5 m*0.5 m. We also explored the relationship between S
      and J' at different sampling scales (from 0.5 m*0.5 m to10 m*10 m) using properly
      measured ramet-mapped data of a10 m*10 m quadrat in the natural community. We
      found that S was negatively corrected with J' at the scales of 0.5 m*0.5 m to 2
      m*2 m, but such a relationships disappeared at relative larger scales (>=2 m*4
      m). When fitting different species abundance models combined with trait-specific
      methods, we found that niche preemption may be the determining mechanism of
      species evenness along the succession gradient. Considering all results together,
      we can conclude that such niche differentiation and spatial scale effects may
      help to explain the maintenance of high species richness in sub-alpine meadow
      communities.

PMID- 23152846
TI  - Effects of ginger and expectations on symptoms of nausea in a balanced placebo
      design.
AB  - OBJECTIVE: Ginger effects on (experimental) nausea have been described, but also
      strong placebo effects and sex differences when nausea is involved. The "balanced
      placebo design" has been proposed to allow better separation of drug and placebo
      effects. METHODS: Sixty-four healthy participants (32 women) were randomly
      assigned to receive an antiemetic ginger preparation or placebo, and half of each
      group was told to have received drug or placebo. They were exposed to 5*2 min
      body rotations to induce nausea. Subjective symptoms and behavioral (rotation
      tolerance, head movements) and physiological measures (electrogastrogram,
      cortisol) were recorded. Groups were balanced for sex of participants and
      experimenters. RESULTS: Ginger and the information given did not affect any
      outcome measure, and previous sex differences could not be confirmed. Adding the
      experimenters revealed a significant four-factorial interaction on behavioral but
      not on subjective or physiological measures Men who received placebo responded to
      placebo information when provided by the male experimenter, and to ginger
      information when provided by the female experimenter. This effect was not
      significant in women. CONCLUSION: The effects of an antiemetic drug and provided
      information interact with psychosocial variables of participants and
      experimenters in reports of nausea.

PMID- 23152847
TI  - The aldosterone-mineralocorticoid receptor pathway exerts anti-inflammatory
      effects in endotoxin-induced uveitis.
AB  - We have previously shown that the eye is a mineralocorticoid-sensitive organ and
      we now question the role of mineralocorticoid receptor (MR) in ocular
      inflammation. The endotoxin-induced uveitis (EIU), a rat model of human
      intraocular inflammation, was induced by systemic administration of
      lipopolysaccharide (LPS). Evaluations were made 6 and 24 hours after intraocular
      injection of aldosterone (simultaneous to LPS injection). Three hours after onset
      of EIU, the MR and the glucocorticoid metabolizing enzyme 11-beta hydroxysteroid
      dehydrogenase type 2 (11beta-HSD2) expression were down-regulated in iris/ciliary
      body and the corticosterone concentration was increased in aqueous humor,
      altering the normal MR/glucocorticoid receptor (GR) balance. At 24 hours, the GR
      expression was also decreased. In EIU, aldosterone reduced the intensity of
      clinical inflammation in a dose-dependent manner. The clinical benefit of
      aldosterone was abrogated in the presence of the MR antagonist (RU26752) and only
      partially with the GR antagonist (RU38486). Aldosterone reduced the release of
      inflammatory mediators (6 and 24 hours: TNF-alpha, IFN-gamma, MIP-1alpha) in
      aqueous humor and the number of activated microglia/macrophages. Aldosterone
      partly prevented the uveitis-induced MR down-regulation. These results suggest
      that MR expression and activation in iris/ciliary body could protect the ocular
      structures against damages induced by EIU.

PMID- 23152848
TI  - Development of implant/interconnected porous hydroxyapatite complex as new
      concept graft material.
AB  - BACKGROUND: Dental implant has been successfully used to replace missing teeth.
      However, in some clinical situations, implant placement may be difficult because
      of a large bone defect. We designed novel complex biomaterial to simultaneously
      restore bone and place implant. This complex was incorporated implant into
      interconnected porous calcium hydroxyapatite (IP-CHA). We then tested this
      Implant/IP-CHA complex and evaluated its effect on subsequent bone regeneration
      and implant stability in vivo. METHODOLOGY/PRINCIPAL FINDINGS: A cylinder-type IP
      CHA was used in this study. After forming inside of the cylinder, an implant was
      placed inside to fabricate the Implant/IP-CHA complex. This complex was then
      placed into the prepared bone socket in the femur of four beagle-Labrador hybrid
      dogs. As a control, implants were placed directly into the femur without any bone
      substrate. Bone sockets were allowed to heal for 2, 3 and 6 months and implant
      stability quotients (ISQ) were measured. Finally, tissue blocks containing the
      Implant/IP-CHA complexes were harvested. Specimens were processed for histology
      and stained with toluidine blue and bone implant contact (BIC) was measured. The
      ISQs of complex groups was 77.8+/-2.9 in the 6-month, 72.0+/-5.7 in the 3-month
      and 47.4+/-11.0 in the 2-month. There was no significant difference between the 3
      or 6-month complex groups and implant control groups. In the 2-month group,
      connective tissue, including capillary angiogenesis, was predominant around the
      implants, although newly formed bone could also be observed. While, in the 3 and
      6-month groups, newly formed bone could be seen in contact to most of the implant
      surface. The BICs of complex groups was 2.18+/-3.77 in the 2-month, 44.03+/-29.58
      in the 3-month, and 51.23+/-8.25 in the 6-month. Significant difference was
      detected between the 2 and 6-month. CONCLUSIONS/SIGNIFICANCE: Within the results
      of this study, the IP-CHA/implant complex might be able to achieve both bone
      reconstruction and implant stability.

PMID- 23152849
TI  - Early endogenous activation of CB1 and CB2 receptors after spinal cord injury is
      a protective response involved in spontaneous recovery.
AB  - Spinal cord injury (SCI) induces a cascade of processes that may further expand
      the damage (secondary injury) or, alternatively, may be part of a safeguard
      response. Here we show that after a moderate-severe contusive SCI in rats there
      is a significant and very early increase in the spinal cord content of the
      endocannabinoids 2-arachidonoylglycerol (2-AG) and arachidonoyl ethanolamide
      (anandamide, AEA). Since 2-AG and AEA act through CB1 and CB2 cannabinoid
      receptors, we administered at 20 minutes after lesion a single injection of their
      respective antagonists AM281 and AM630 alone or in combination to block the
      effects of this early endocannabinoid accumulation. We observed that AM281, AM630
      or AM281 plus AM630 administration impairs the spontaneous motor recovery of rats
      according to the Basso-Beattie-Bresnahan (BBB) locomotor scale. However, blockade
      of CB1, CB2 or both receptors produced different effects at the histopathological
      level. Thus, AM630 administration results at 90 days after lesion in increased
      MHC-II expression by spinal cord microglia/monocytes and reduced number of
      serotoninergic fibres in lumbar spinal cord (below the lesion). AM281 exerted the
      same effects but also increased oedema volume estimated by MRI. Co-administration
      of AM281 and AM630 produced the effects observed with the administration of
      either AM281 or AM630 and also reduced white matter and myelin preservation and
      enhanced microgliosis in the epicentre. Overall, our results suggest that the
      endocannabinoids acting through CB1 and CB2 receptors are part of an early
      neuroprotective response triggered after SCI that is involved in the spontaneous
      recovery after an incomplete lesion.

PMID- 23152850
TI  - IgG responses to Pneumococcal and Haemophilus influenzae protein antigens are not
      impaired in children with a history of recurrent acute otitis media.
AB  - BACKGROUND: Vaccines including conserved antigens from Streptococcus pneumoniae
      and nontypeable Haemophilus influenzae (NTHi) have the potential to reduce the
      burden of acute otitis media. Little is known about the antibody response to such
      antigens in young children with recurrent acute otitis media, however, it has
      been suggested antibody production may be impaired in these children. METHODS: We
      measured serum IgG levels against 4 pneumococcal (PspA1, PspA 2, CbpA and Ply)
      and 3 NTHi (P4, P6 and PD) proteins in a cross-sectional study of 172 children
      under 3 years of age with a history of recurrent acute otitis media (median 7
      episodes, requiring ventilation tube insertion) and 63 healthy age-matched
      controls, using a newly developed multiplex bead assay. RESULTS: Children with a
      history of recurrent acute otitis media had significantly higher geometric mean
      serum IgG levels against NTHi proteins P4, P6 and PD compared with healthy
      controls, whereas there was no difference in antibody levels against pneumococcal
      protein antigens. In both children with and without a history of acute otitis
      media, antibody levels increased with age and were significantly higher in
      children colonised with S. pneumoniae or NTHi compared with children that were
      not colonised. CONCLUSIONS: Proteins from S. pneumoniae and NTHi induce serum IgG
      in children with a history of acute otitis media. The mechanisms in which
      proteins induce immunity and potential protection requires further investigation
      but the dogma of impaired antibody responses in children with recurrent acute
      otitis media should be reconsidered.

PMID- 23152851
TI  - Effects of slow deep breathing at high altitude on oxygen saturation, pulmonary
      and systemic hemodynamics.
AB  - Slow deep breathing improves blood oxygenation (Sp(O2)) and affects hemodynamics
      in hypoxic patients. We investigated the ventilatory and hemodynamic effects of
      slow deep breathing in normal subjects at high altitude. We collected data in
      healthy lowlanders staying either at 4559 m for 2-3 days (Study A; N = 39) or at
      5400 m for 12-16 days (Study B; N = 28). Study variables, including Sp(O2) and
      systemic and pulmonary arterial pressure, were assessed before, during and after
      15 minutes of breathing at 6 breaths/min. At the end of slow breathing, an
      increase in Sp(O2) (Study A: from 80.2+/-7.7% to 89.5+/-8.2%; Study B: from
      81.0+/-4.2% to 88.6+/-4.5; both p<0.001) and significant reductions in systemic
      and pulmonary arterial pressure occurred. This was associated with increased
      tidal volume and no changes in minute ventilation or pulmonary CO diffusion. Slow
      deep breathing improves ventilation efficiency for oxygen as shown by blood
      oxygenation increase, and it reduces systemic and pulmonary blood pressure at
      high altitude but does not change pulmonary gas diffusion.

PMID- 23152852
TI  - A 3.7 Mb deletion encompassing ZEB2 causes a novel polled and multisystemic
      syndrome in the progeny of a somatic mosaic bull.
AB  - Polled and Multisystemic Syndrome (PMS) is a novel developmental disorder
      occurring in the progeny of a single bull. Its clinical spectrum includes
      polledness (complete agenesis of horns), facial dysmorphism, growth delay,
      chronic diarrhea, premature ovarian failure, and variable neurological and
      cardiac anomalies. PMS is also characterized by a deviation of the sex-ratio,
      suggesting male lethality during pregnancy. Using Mendelian error mapping and
      whole-genome sequencing, we identified a 3.7 Mb deletion on the paternal bovine
      chromosome 2 encompassing ARHGAP15, GTDC1 and ZEB2 genes. We then produced
      control and affected 90-day old fetuses to characterize this syndrome by
      histological and expression analyses. Compared to wild type individuals, affected
      animals showed a decreased expression of the three deleted genes. Based on a
      comparison with human Mowat-Wilson syndrome, we suggest that deletion of ZEB2, is
      responsible for most of the effects of the mutation. Finally sperm-FISH, embryo
      genotyping and analysis of reproduction records confirmed somatic mosaicism in
      the founder bull and male-specific lethality during the first third of gestation.
      In conclusion, we identified a novel locus involved in bovid horn ontogenesis and
      suggest that epithelial-to-mesenchymal transition plays a critical role in horn
      bud differentiation. We also provide new insights into the pathogenicity of ZEB2
      loss of heterozygosity in bovine and humans and describe the first case of male
      specific lethality associated with an autosomal locus in a non-murine mammalian
      species. This result sets PMS as a unique model to study sex-specific gene
      expression/regulation.

PMID- 23152854
TI  - Gene size matters.
AB  - In this work we show that in genome-wide association studies (GWAS) there is a
      strong bias favoring of genes covered by larger numbers of SNPs. Thus, we state
      here that there is a need for correction for such bias when performing downstream
      gene-level analysis, e.g. pathway analysis and gene-set analysis. We investigate
      several methods of obtaining gene level statistical significance in GWAS, and
      compare their effectiveness in correcting such bias. We also propose a simple
      algorithm based on first order statistic that corrects such bias.

PMID- 23152853
TI  - ScFv anti-heparan sulfate antibodies unexpectedly activate endothelial and cancer
      cells through p38 MAPK: implications for antibody-based targeting of heparan
      sulfate proteoglycans in cancer.
AB  - Tumor development requires angiogenesis and anti-angiogenic therapies have been
      introduced in the treatment of cancer. In this context, heparan sulfate
      proteoglycans (HSPGs) emerge as interesting targets, owing to their function as
      co-receptors of major, pro-angiogenic factors. Accordingly, previous studies have
      suggested anti-tumor effects of heparin, i.e. over-sulfated HS, and various
      heparin mimetics; however, a significant drawback is their unspecific mechanism
      of action and potentially serious side-effects related to their anticoagulant
      properties. Here, we have explored the use of human ScFv anti-HS antibodies
      (alphaHS) as a more rational approach to target HSPG function in endothelial
      cells (ECs). alphaHS were initially selected for their recognition of HS epitopes
      localized preferentially to the vasculature of patient glioblastoma tumors, i.e.
      highly angiogenic brain tumors. Unexpectedly, we found that these alphaHS
      exhibited potent pro-angiogenic effects in primary human ECs. alphaHS were shown
      to stimulate EC differentiation, which was associated with increased EC tube
      formation and proliferation. Moreover, alphaHS supported EC survival under
      hypoxia and starvation, i.e. conditions typical of the tumor microenvironment.
      Importantly, alphaHS-mediated proliferation was efficiently counter-acted by
      heparin and was absent in HSPG-deficient mutant cells, confirming HS-specific
      effects. On a mechanistic level, binding of alphaHS to HSPGs of ECs as well as
      glioblastoma cells was found to trigger p38 MAPK-dependent signaling resulting in
      increased proliferation. We conclude that several alphaHS that recognize HS
      epitopes abundant in the tumor vasculature may elicit a pro-angiogenic response,
      which has implications for the development of antibody-based targeting of HSPGs
      in cancer.

PMID- 23152855
TI  - Virtual touch tissue quantification of acoustic radiation force impulse: a new
      ultrasound elastic imaging in the diagnosis of thyroid nodules.
AB  - OBJECTIVE: Virtual touch tissue quantification (VTQ) of acoustic radiation force
      impulse (ARFI) is a new quantitative technique to measure tissue stiffness. The
      study was aimed to assess the usefulness of VTQ in the diagnosis of thyroid
      nodules. METHODS: 173 pathologically proven thyroid nodules in 142 patients were
      included and all were examined by conventional ultrasound (US), conventional
      elasticity imaging (EI) and VTQ of ARFI. The tissue stiffness for VTQ was
      expressed as shear wave velocity (SWV) (m/s). Receiver-operating characteristic
      curve (ROC) analyses were performed to assess the diagnostic performance. Intra-
      and inter-observer reproducibility of VTQ measurement was assessed. RESULTS: The
      SWVs of benign and malignant thyroid nodules were 2.34+/-1.17 m/s (range: 0.61
      9.00 m/s) and 4.82+/-2.53 m/s (range: 2.32-9.00 m/s) respectively (P<0.001). The
      mean SWV ratios between each nodule and the adjacent thyroid tissue were 1.19+/
      0.67 (range: 0.31-6.87) for benign and 2.50+/-1.54 (range: 0.85-6.69) for
      malignant nodules (P<0.001). ROC analyses indicated that the area under the curve
      was 0.861 (95% CI : 0.804, 0.918) (P<0.001) for SWV and 0.831(95% CI : 0.761,
      0.900)(P<0.001) for the SWV ratio. The cutoff points for the differential
      diagnosis were 2.87 m/s for SWV and 1.59 for SWV ratio. The sensitivity,
      specificity, accuracy, positive predictive value, and negative predictive value
      for EI were 65.9%, 66.7%, 66.5%, 40.3%, and 85.1%, respectively, and were 63.6%
      75%, 82.2%-88.4%, 80.3%-82.1%, 58.9%-65.1%, and 87.7%-90.5%, respectively, for
      VTQ. The diagnostic value of VTQ is the highest for nodules >20 mm and lowest for
      those <=10 mm. The correlation coefficients were 0.904 for intraobserver
      measurement and 0.864 for interobserver measurement. CONCLUSIONS: VTQ of ARFI
      provides quantitative and reproducible information about the tissue stiffness,
      which is useful for the differentiation between benign and malignant thyroid
      nodules. The diagnostic performance of VTQ is higher than that of conventional
      EI.

PMID- 23152857
TI  - Fish utilisation of wetland nurseries with complex hydrological connectivity.
AB  - The physical and faunal characteristics of coastal wetlands are driven by
      dynamics of hydrological connectivity to adjacent habitats. Wetlands on estuary
      floodplains are particularly dynamic, driven by a complex interplay of tidal
      marine connections and seasonal freshwater flooding, often with unknown
      consequences for fish using these habitats. To understand the patterns and
      subsequent processes driving fish assemblage structure in such wetlands, we
      examined the nature and diversity of temporal utilisation patterns at a species
      or genus level over three annual cycles in a tropical Australian estuarine
      wetland system. Four general patterns of utilisation were apparent based on CPUE
      and size-structure dynamics: (i) classic nursery utlisation (use by recently
      settled recruits for their first year) (ii) interrupted peristence (iii) delayed
      recruitment (iv) facultative wetland residence. Despite the small self-recruiting
      'facultative wetland resident' group, wetland occupancy seems largely driven by
      connectivity to the subtidal estuary channel. Variable connection regimes (i.e.
      frequency and timing of connections) within and between different wetland units
      (e.g. individual pools, lagoons, swamps) will therefore interact with the
      diversity of species recruitment schedules to generate variable wetland
      assemblages in time and space. In addition, the assemblage structure is heavily
      modified by freshwater flow, through simultaneously curtailing persistence of the
      'interrupted persistence' group, establishing connectivity for freshwater spawned
      members of both the 'facultative wetland resident' and 'delayed recruitment
      group', and apparently mediating use of intermediate nursery habitats for marine
      spawned members of the 'delayed recruitment' group. The diversity of utilisation
      pattern and the complexity of associated drivers means assemblage compositions,
      and therefore ecosystem functioning, is likely to vary among years depending on
      variations in hydrological connectivity. Consequently, there is a need to
      incorporate this diversity into understandings of habitat function, conservation
      and management.

PMID- 23152856
TI  - Involvement of Aquaporin 3 in Helicobacter pylori-related gastric diseases.
AB  - BACKGROUND: Gastric cancer is one of the most common and lethal malignant cancers
      worldwide, and numerous epidemiological studies have demonstrated that
      Helicobacter pylori (H. pylori) infection plays a key role in the development of
      gastric carcinomas. Our previous studies showed that aquaporin 3 (AQP3) is
      overexpressed in gastric carcinoma and promotes the migration and proliferation
      of human gastric carcinoma cells, suggesting that AQP3 may be a potentially
      important determinant of gastric carcinoma. However, the role of AQP3 in H.
      pylori carcinogenesis is unknown. METHODS: The AQP3 protein and H. pylori were
      detected in human gastric tissues by immunohistochemistry and modified Giemsa
      staining respectively. AQP3 knockdown was obtained by small interfering (si) RNA.
      Western blot assays and RT-PCR were used to evaluate the change of AQP3 in the
      human gastric cancer AGS and SGC7901 cell lines after co-culture with H. pylori.
      Sprague Dawley rats were orally inoculated with H. pylori to establish a rat
      model colonized by H. pylori. RESULTS: The present study found that AQP3
      expression correlated with H. pylori infection status in gastric cancer tissues
      and corresponding normal mucosa, and H. pylori co-culture upregulated AQP3
      expression in human gastric adenocarcinoma cells in vitro via the extracellular
      signal-regulated kinase signaling pathway. H. pylori infection also increased
      AQP3 expression in gastric mucosa colonized by H. pylori in a Sprague Dawley rat
      model. CONCLUSIONS: These findings provide further information to understand the
      mechanism of H. pylori carcinogenesis and a potential strategy for the treatment
      of H. pylori-associated gastric carcinoma.

PMID- 23152858
TI  - Generation of artificial FASTQ files to evaluate the performance of next
      generation sequencing pipelines.
AB  - Pipelines for the analysis of Next-Generation Sequencing (NGS) data are generally
      composed of a set of different publicly available software, configured together
      in order to map short reads of a genome and call variants. The fidelity of
      pipelines is variable. We have developed ArtificialFastqGenerator, which takes a
      reference genome sequence as input and outputs artificial paired-end FASTQ files
      containing Phred quality scores. Since these artificial FASTQs are derived from
      the reference genome, it provides a gold-standard for read-alignment and variant
      calling, thereby enabling the performance of any NGS pipeline to be evaluated.
      The user can customise DNA template/read length, the modelling of coverage based
      on GC content, whether to use real Phred base quality scores taken from existing
      FASTQ files, and whether to simulate sequencing errors. Detailed coverage and
      error summary statistics are outputted. Here we describe ArtificialFastqGenerator
      and illustrate its implementation in evaluating a typical bespoke NGS analysis
      pipeline under different experimental conditions. ArtificialFastqGenerator was
      released in January 2012. Source code, example files and binaries are freely
      available under the terms of the GNU General Public License v3.0. from
      https://sourceforge.net/projects/artfastqgen/.

PMID- 23152859
TI  - Automated masking of AFLP markers improves reliability of phylogenetic analyses.
AB  - The amplified fragment length polymorphisms (AFLP) method has become an
      attractive tool in phylogenetics due to the ease with which large numbers of
      characters can be generated. In contrast to sequence-based phylogenetic
      approaches, AFLP data consist of anonymous multilocus markers. However, potential
      artificial amplifications or amplification failures of fragments contained in the
      AFLP data set will reduce AFLP reliability especially in phylogenetic inferences.
      In the present study, we introduce a new automated scoring approach, called
      "AMARE" (AFLP MAtrix REduction). The approach is based on replicates and makes
      marker selection dependent on marker reproducibility to control for scoring
      errors. To demonstrate the effectiveness of our approach we record error rate
      estimations, resolution scores, PCoA and stemminess calculations. As in general
      the true tree (i.e. the species phylogeny) is not known, we tested AMARE with
      empirical, already published AFLP data sets, and compared tree topologies of
      different AMARE generated character matrices to existing phylogenetic trees
      and/or other independent sources such as morphological and geographical data. It
      turns out that the selection of masked character matrices with highest resolution
      scores gave similar or even better phylogenetic results than the original AFLP
      data sets.

PMID- 23152860
TI  - Effect of environmental and lifestyle factors on hypertension: Shimane COHRE
      study.
AB  - BACKGROUND: In recent years there has been increasing evidence of an association
      between residential remoteness and hypertension (HTN); however, no study has
      examined the effects of residential remoteness-lifestyle associations on HTN. The
      objective of this study was to evaluate the effects of residential remoteness, as
      measured by road network distance and elevation, and lifestyle associations,
      including access to daily products as a measure of car use, on HTN in a rural
      region in Japan. METHOD: This is a cross-sectional population based study. We
      analyzed data from the Shimane COHRE study conducted from 2006 to 2009 in the
      rural mountainous regions of Japan. After excluding missing data, we conducted a
      logistic regression analysis of the data for 1,348 individuals and examined the
      effects of residential remoteness and lifestyle associations, including road
      network distance, elevation and access to daily products as a measure of car use,
      on the prevalence of HTN. PRINCIPAL FINDINGS: In participants without access to
      car use, the odds ratios for self-reported HTN (i.e. taking antihypertensive
      medication) were significantly increased in those living in moderate (odds ratio
      (OR): 2.21, 95% confidence interval (CI): 1.19-4.08) and far (OR: 2.55, 95% CI:
      1.00-6.51) road distances, whereas there were no significant associations in
      participants with access to car use. There were no significant associations
      between elevation and HTN for participants either with or without access to car
      transportation. CONCLUSIONS: Our findings show that specific residential
      remoteness-hypertension associations vary according to access to daily products
      as a measure of car use in a rural mountainous area of Japan. These results
      advance the understanding and importance of considering residential environment,
      "where people live," in establishing health policy.

PMID- 23152861
TI  - IL12RB2 gene is associated with the age of type 1 diabetes onset in Croatian
      family Trios.
AB  - BACKGROUND: Common complex diseases are influenced by both genetic and
      environmental factors. Many genetic factors overlap between various autoimmune
      diseases. The aim of the present study is to determine whether four genetic
      variants known to be risk variants for several autoimmune diseases could be
      associated with an increased susceptibility to type 1 diabetes mellitus. METHODS
      AND FINDINGS: We genotyped four genetic variants (rs2358817, rs1049550,
      rs6679356, rs9865818) within VTCN1, ANXA11, IL12RB2 and LPP genes respectively,
      in 265 T1DM family trios in Croatian population. We did not detect association of
      these polymorphisms with T1DM. However, quantitative transmission disequilibrium
      test (QTDT, orthogonal model) revealed a significant association between the age
      of onset of T1DM and IL12RB2 rs6679356 variant. An earlier onset of T1DM was
      associated with the rs6679356 minor dominant allele C (p = 0.005). The
      association remained significant even after the Bonferroni correction for
      multiple testing and permutation. CONCLUSIONS: Variants originally associated
      with juvenile idiopathic arthritis (VTCN1 gene), sarcoidosis (ANXA11 gene),
      primary biliary cirrhosis (IL12RB2 gene) and celiac disease (LPP gene) were not
      associated with type 1 diabetes in our dataset. Nevertheless, association of
      IL12RB2 rs6679356 polymorphism with the age of T1DM onset suggests that this gene
      plays a role in defining the time of disease onset.

PMID- 23152862
TI  - Difference in agr dysfunction and reduced vancomycin susceptibility between MRSA
      bacteremia involving SCCmec types IV/IVa and I-III.
AB  - BACKGROUND: Dysfunction of agr, with reduced susceptibility or hetero-resistance
      to vancomycin, is thought to be associated with a worse outcome of methicillin
      resistant Staphylococcus aureus (MRSA) bacteremia (MRSAB). However, the
      difference in agr dysfunction according to the SCCmec type in MRSA infection is
      undetermined. We compared the prevalence of agr dysfunction, reduced vancomycin
      susceptibility and the outcomes of SCCmec IV/IVa and I-III MRSAB. METHODS: The
      study included 307 cases of MRSAB. SCCmec types were determined by multiplex PCR.
      The clinical and microbiological features and outcomes of 58 SCCmec IV/IVa MRSAB
      were compared with those of 249 SCCmec I-III MRSAB. RESULTS: Compared with SCCmec
      I-III MRSAB, SCCmec IV/IVa MRSAB was associated with lower rates of agr
      dysfunction (3% vs. 43%), vancomycin minimum inhibitory concentration (MIC) = 2
      ug/mL (3% vs. 15%), and hetero-resistance to vancomycin (0% vs. 8%) (all P<0.05).
      However, the 30-day and S. aureus-related mortality in patients with SCCmec
      IV/IVa MRSAB were not different from those in patients with SCCmec I-III MRSAB in
      multivariate analyses (HR 1.168, 95% CI 0.705-1.938; HR 1.025, 95% CI 0.556
      1.889). CONCLUSIONS: SCCmec IV/IVa MRSAB was associated with lower rates of agr
      dysfunction and hetero-resistance to vancomycin and a lower vancomycin MIC,
      compared with SCCmec I-III MRSAB. However, the outcomes of SCCmec IV/IVa MRSAB
      did not differ from those of SCCmec I-III MRSAB.

PMID- 23152863
TI  - Galectin-3 impairment of MYCN-dependent apoptosis-sensitive phenotype is
      antagonized by nutlin-3 in neuroblastoma cells.
AB  - MYCN amplification occurs in about 20-25% of human neuroblastomas and
      characterizes the majority of the high-risk cases, which display less than 50%
      prolonged survival rate despite intense multimodal treatment. Somehow
      paradoxically, MYCN also sensitizes neuroblastoma cells to apoptosis,
      understanding the molecular mechanisms of which might be relevant for the therapy
      of MYCN amplified neuroblastoma. We recently reported that the apoptosis
      sensitive phenotype induced by MYCN is linked to stabilization of p53 and its
      proapoptotic kinase HIPK2. In MYCN primed neuroblastoma cells, further activation
      of both HIPK2 and p53 by Nutlin-3 leads to massive apoptosis in vitro and to
      tumor shrinkage and impairment of metastasis in xenograft models. Here we report
      that Galectin-3 impairs MYCN-primed and HIPK2-p53-dependent apoptosis in
      neuroblastoma cells. Galectin-3 is broadly expressed in human neuroblastoma cell
      lines and tumors and is repressed by MYCN to induce the apoptosis-sensitive
      phenotype. Despite its reduced levels, Galectin-3 can still exert residual
      antiapoptotic effects in MYCN amplified neuroblastoma cells, possibly due to its
      specific subcellular localization. Importantly, Nutlin-3 represses Galectin-3
      expression, and this is required for its potent cell killing effect on MYCN
      amplified cell lines. Our data further characterize the apoptosis-sensitive
      phenotype induced by MYCN, expand our understanding of the activity of MDM2-p53
      antagonists and highlight Galectin-3 as a potential biomarker for the tailored
      p53 reactivation therapy in patients with high-risk neuroblastomas.

PMID- 23152864
TI  - Longitudinal study of mammary epithelial and fibroblast co-cultures using optical
      coherence tomography reveals morphological hallmarks of pre-malignancy.
AB  - The human mammary gland is a complex and heterogeneous organ, where the
      interactions between mammary epithelial cells (MEC) and stromal fibroblasts are
      known to regulate normal biology and tumorigenesis. We aimed to longitudinally
      evaluate morphology and size of organoids in 3D co-cultures of normal (MCF10A) or
      pre-malignant (MCF10DCIS.com) MEC and hTERT-immortalized fibroblasts from
      reduction mammoplasty (RMF). This co-culture model, based on an isogenic panel of
      cell lines, can yield insights to understand breast cancer progression. However,
      3D cultures pose challenges for quantitative assessment and imaging, especially
      when the goal is to measure the same organoid structures over time. Using optical
      coherence tomography (OCT) as a non-invasive method to longitudinally quantify
      morphological changes, we found that OCT provides excellent visualization of MEC
      fibroblast co-cultures as they form ductal acini and remodel over time. Different
      concentrations of fibroblasts and MEC reflecting reported physiological ratios
      [1] were evaluated, and we found that larger, hollower, and more aspherical acini
      were formed only by pre-malignant MEC (MCF10DCIS.com) in the presence of
      fibroblasts, whereas in comparable conditions, normal MEC (MCF10A) acini remained
      smaller and less aspherical. The ratio of fibroblast to MEC was also influential
      in determining organoid phenotypes, with higher concentrations of fibroblasts
      producing more aspherical structures in MCF10DCIS.com. These findings suggest
      that stromal-epithelial interactions between fibroblasts and MEC can be modeled
      in vitro, with OCT imaging as a convenient means of assaying time dependent
      changes, with the potential for yielding important biological insights about the
      differences between benign and pre-malignant cells.

PMID- 23152865
TI  - Determining the precise cerebral response to acupuncture: an improved FMRI study.
AB  - BACKGROUND: In acupuncture brain imaging trials, there are many non-acupuncture
      factors confounding the neuronal mapping. The modality of the placebo, subjects'
      psychological attitude to acupuncture and their physical state are the three most
      confounding factors. OBJECTIVE: To obtain more precise and accurate cerebral fMRI
      mapping of acupuncture. DESIGN AND SETTING: A 2*2 randomized, controlled,
      participant-blinded cross-over factorial acupuncture trial was conducted at
      Xuanwu Hospital in Beijing, China. PARTICIPANTS: Forty-one college students with
      myopia were recruited to participate in our study and were allocated randomly to
      four groups, Group A, Group B, Group C and Group D. INTERVENTIONS: Group A
      received real acupuncture (RA) and treatment instruction (TI); Group B received
      RA and non-treatment instruction (NI); Group C received sham acupuncture (SA) and
      TI; Group D received SA and NI. RESULTS: Stimulation at LR3 activated some areas
      of the visual cortex, and the cerebral response to non-acupuncture factors was
      complex and occurred in multiple areas. CONCLUSIONS: The results provide more
      evidence regarding the credibility of acupuncture therapy and suggest that more
      precise experimental designs are needed to eliminate sources of bias in
      acupuncture controlled trials and to obtain sound results.

PMID- 23152867
TI  - The citation merit of scientific publications.
AB  - We propose a new method to assess the merit of any set of scientific papers in a
      given field based on the citations they receive. Given a field and a citation
      impact indicator, such as the mean citation or the [Formula: see text]-index, the
      merit of a given set of [Formula: see text] articles is identified with the
      probability that a randomly drawn set of [Formula: see text] articles from a
      given pool of articles in that field has a lower citation impact according to the
      indicator in question. The method allows for comparisons between sets of articles
      of different sizes and fields. Using a dataset acquired from Thomson Scientific
      that contains the articles published in the periodical literature in the period
      1998-2007, we show that the novel approach yields rankings of research units
      different from those obtained by a direct application of the mean citation or the
      [Formula: see text]-index.

PMID- 23152866
TI  - Interaction between maternal passive smoking during pregnancy and CYP1A1 and GSTs
      polymorphisms on spontaneous preterm delivery.
AB  - OBJECTIVE: The present study aimed to examine the association between maternal
      passive smoking during pregnancy and the risk of spontaneous PTD and to explore
      the potential interaction of the single or joint gene polymorphism of CYP1A1 and
      GSTs with maternal passive smoking on the risk of spontaneous PTD. METHOD: We
      investigated whether the association between maternal passive smoking and PTD can
      be modified by 2 metabolic genes, i.e. cytochrome P4501A1 (CYP1A1) and
      glutathione S-transferases (GSTs), in a case-control study with 198 spontaneous
      preterm and 524 term deliveries in Shenzhen and Foshan, China. We used logistic
      regression to test gene-passive smoking interaction, adjusting for maternal socio
      demographics and prepregnancy body mass index. RESULTS: Overall, maternal passive
      smoking during pregnancy was associated with higher risk of PTD (adjusted odds
      ratio = 2.20 [95% confidence interval: 1.56-3.12]). This association was modified
      by CYP1A1 and GSTs together, but not by any single genotype. For cross-categories
      of CYP1A1 Msp I and GSTs, maternal passive smoking was associated with higher
      risk of PTD among those women with CYP1A1 "TC/CC"+ GSTs "null", but not among
      women with other genotypes; and this interaction was significant (OR = 2.66 [95%
      CI: 1.19-5.97]; P-value: 0.017). For cross-categories of CYP1A1 BsrD I and GSTs,
      maternal passive smoking was associated with higher risk of PTD only among those
      women with CYP1A1"AG/GG"+ GSTs "null", but not among women with other genotypes;
      and this interaction was significant (OR = 3.00 [95% CI: 1.17-7.74]; P-value:
      0.023). CONCLUSIONS: Our findings suggest that the combined genotypes of CYP1A1
      and GSTs can help to identify vulnerable pregnant women who are subject to high
      risk of spontaneous PTD due to passive smoking.

PMID- 23152868
TI  - A fast EM algorithm for BayesA-like prediction of genomic breeding values.
AB  - Prediction accuracies of estimated breeding values for economically important
      traits are expected to benefit from genomic information. Single nucleotide
      polymorphism (SNP) panels used in genomic prediction are increasing in density,
      but the Markov Chain Monte Carlo (MCMC) estimation of SNP effects can be quite
      time consuming or slow to converge when a large number of SNPs are fitted
      simultaneously in a linear mixed model. Here we present an EM algorithm (termed
      "fastBayesA") without MCMC. This fastBayesA approach treats the variances of SNP
      effects as missing data and uses a joint posterior mode of effects compared to
      the commonly used BayesA which bases predictions on posterior means of effects.
      In each EM iteration, SNP effects are predicted as a linear combination of best
      linear unbiased predictions of breeding values from a mixed linear animal model
      that incorporates a weighted marker-based realized relationship matrix. Method
      fastBayesA converges after a few iterations to a joint posterior mode of SNP
      effects under the BayesA model. When applied to simulated quantitative traits
      with a range of genetic architectures, fastBayesA is shown to predict GEBV as
      accurately as BayesA but with less computing effort per SNP than BayesA. Method
      fastBayesA can be used as a computationally efficient substitute for BayesA,
      especially when an increasing number of markers bring unreasonable computational
      burden or slow convergence to MCMC approaches.

PMID- 23152869
TI  - Common FLG mutation K4671X not associated with atopic dermatitis in Han Chinese
      in a family association study.
AB  - BACKGROUND: Filaggrin gene (FLG) mutations have been identified as the cause of
      ichthyosis vulgaris (IV) and major predisposing factors for atopic dermatitis
      (AD). The relationship among AD, IV and FLG mutations has not been clarified yet.
      Mutations 3321delA and K4671X, two of the most common mutations in Chinese
      patients, were both statistically associated with AD in case-control studies.
      MATERIALS AND METHODS: A group of 100 family trios (a total of 300 members with
      one affected AD proband and both parents) were recruited and screened for three
      filaggrin null mutations (3222del4, 3321delA and K4671X). The subjects'
      manifestations of AD and IV were assessed by two experienced dermatologists and
      recorded in detail. The relationship of common mutations to AD were assessed
      using both case-control and family-based tests of association. Filaggrin
      expression was measured in skin of 3 subjects with K4671X heterozygote and the
      normal control using quantitative real-time RT-PCR and immunohistochemistry.
      RESULTS: Of 100 probands for AD, 22 were carriers for common FLG mutations and
      only 2 of them were from 40 none-IV family trios (5.00%), consistent with that of
      the healthy control group (3.99%, P>0.05). Significant statistical associations
      were revealed between AD and 3321delA (P<0.001, odds ratio 12.28, 95% confidence
      interval 3.35-44.98) as well as K4671X (P = 0.002, odds ratio 4.53, 95%
      confidence interval 1.77-11.60). The family-based approach revealed that 3321delA
      was over-transmitted to AD offspring from parents (T:U = 12?1, P = 0.003) but
      failed to demonstrate transmission disequilibrium between K4671X and AD (T:U =
      10?8, P = 0.815). Moreover, compared to the normal control, filaggrin expression
      at both mRNA and protein levels in epidermis of subjects with K4671X(heter) was
      not reduced. CONCLUSIONS: AD patients from none-IV family trios have low
      probability of carrying FLG mutations. The present family samples confirmed the
      susceptibility of mutation 3321delA to AD in Han Chinese. K4671X was not a
      pathogenic mutation.

PMID- 23152870
TI  - Transcriptome profiling reveals stage-specific production and requirement of
      flagella during biofilm development in Bordetella bronchiseptica.
AB  - We have used microarray analysis to study the transcriptome of the bacterial
      pathogen Bordetella bronchiseptica over the course of five time points
      representing distinct stages of biofilm development. The results suggest that B.
      bronchiseptica undergoes a coordinately regulated gene expression program similar
      to a bacterial developmental process. Expression and subsequent production of the
      genes encoding flagella, a classical Bvg(-) phase phenotype, occurs and is under
      tight regulatory control during B. bronchiseptica biofilm development. Using
      mutational analysis, we demonstrate that flagella production at the appropriate
      stage of biofilm development, i.e. production early subsequently followed by
      repression, is required for robust biofilm formation and maturation. We also
      demonstrate that flagella are necessary and enhance the initial cell-surface
      interactions, thereby providing mechanistic information on the initial stages of
      biofilm development for B. bronchiseptica. Biofilm formation by B. bronchiseptica
      involves the production of both Bvg-activated and Bvg-repressed factors followed
      by the repression of factors that inhibit formation of mature biofilms.

PMID- 23152872
TI  - Engineering tocopherol selectivity in alpha-TTP: a combined in vitro/in silico
      study.
AB  - We present a combined in vitro/in silico study to determine the molecular origin
      of the selectivity of [Formula: see text]-tocopherol transfer protein ([Formula:
      see text]-TTP) towards [Formula: see text]-tocopherol. Molecular dynamics
      simulations combined to free energy perturbation calculations predict a binding
      free energy for [Formula: see text]-tocopherol to [Formula: see text]-TTP
      8.26[Formula: see text]2.13 kcal mol[Formula: see text] lower than that of
      [Formula: see text]-tocopherol. Our calculations show that [Formula: see text]
      tocopherol binds to [Formula: see text]-TTP in a significantly distorted geometry
      as compared to that of the natural ligand. Variations in the hydration of the
      binding pocket and in the protein structure are found as well. We propose a
      mutation, A156L, which significantly modifies the selectivity properties of
      [Formula: see text]-TTP towards the two tocopherols. In particular, our
      simulations predict that A156L binds preferentially to [Formula: see text]
      tocopherol, with striking structural similarities to the wild-type-[Formula: see
      text]-tocopherol complex. The affinity properties are confirmed by differential
      scanning fluorimetry as well as in vitro competitive binding assays. Our data
      indicate that residue A156 is at a critical position for determination of the
      selectivity of [Formula: see text]-TTP. The engineering of TTP mutants with
      modulating binding properties can have potential impact at industrial level for
      easier purification of single tocopherols from vitamin E mixtures coming from
      natural oils or synthetic processes. Moreover, the identification of a [Formula:
      see text]-tocopherol selective TTP offers the possibility to challenge the
      hypotheses for the evolutionary development of a mechanism for [Formula: see
      text]-tocopherol selection in omnivorous animals.

PMID- 23152871
TI  - Expression profiles of mitochondrial genes in the frontal cortex and the caudate
      nucleus of developing humans and mice selectively bred for high and low fear.
AB  - A growing body of evidence suggests that mitochondrial function may be important
      in brain development and psychiatric disorders. However, detailed expression
      profiles of those genes in human brain development and fear-related behavior
      remain unclear. Using microarray data available from the public domain and the
      Gene Ontology analysis, we identified the genes and the functional categories
      associated with chronological age in the prefrontal cortex (PFC) and the caudate
      nucleus (CN) of psychiatrically normal humans ranging in age from birth to 50
      years. Among those, we found that a substantial number of genes in the PFC (115)
      and the CN (117) are associated with the GO term: mitochondrion (FDR qv <0.05). A
      greater number of the genes in the PFC (91%) than the genes in the CN (62%)
      showed a linear increase in expression during postnatal development. Using
      quantitative PCR, we validated the developmental expression pattern of four genes
      including monoamine oxidase B (MAOB), NADH dehydrogenase flavoprotein (NDUFV1),
      mitochondrial uncoupling protein 5 (SLC25A14) and tubulin beta-3 chain (TUBB3).
      In mice, overall developmental expression pattern of MAOB, SLC25A14 and TUBB3 in
      the PFC were comparable to the pattern observed in humans (p<0.05). However, mice
      selectively bred for high fear did not exhibit normal developmental changes of
      MAOB and TUBB3. These findings suggest that the genes associated with
      mitochondrial function in the PFC play a significant role in brain development
      and fear-related behavior.

PMID- 23152873
TI  - Nucleotide excision repair is associated with the replisome and its efficiency
      depends on a direct interaction between XPA and PCNA.
AB  - Proliferating cell nuclear antigen (PCNA) is an essential protein for DNA
      replication, DNA repair, cell cycle regulation, chromatin remodeling, and
      epigenetics. Many proteins interact with PCNA through the PCNA interacting
      peptide (PIP)-box or the newly identified AlkB homolog 2 PCNA interacting motif
      (APIM). The xeroderma pigmentosum group A (XPA) protein, with a central but
      somewhat elusive role in nucleotide excision repair (NER), contains the APIM
      sequence suggesting an interaction with PCNA. With an in vivo based approach,
      using modern techniques in live human cells, we show that APIM in XPA is a
      functional PCNA interacting motif and that efficient NER of UV lesions is
      dependent on an intact APIM sequence in XPA. We show that XPA(-/-) cells
      complemented with XPA containing a mutated APIM sequence have increased UV
      sensitivity, reduced repair of cyclobutane pyrimidine dimers and (6-4)
      photoproducts, and are consequently more arrested in S phase as compared to XPA(
      /-) cells complemented with wild type XPA. Notably, XPA colocalizes with PCNA in
      replication foci and is loaded on newly synthesized DNA in undamaged cells. In
      addition, the TFIIH subunit XPD, as well as XPF are loaded on DNA together with
      XPA, and XPC and XPG colocalize with PCNA in replication foci. Altogether, our
      results suggest a presence of the NER complex in the vicinity of the replisome
      and a novel role of NER in post-replicative repair.

PMID- 23152874
TI  - Fluorescence lifetime readouts of Troponin-C-based calcium FRET sensors: a
      quantitative comparison of CFP and mTFP1 as donor fluorophores.
AB  - We have compared the performance of two Troponin-C-based calcium FRET sensors
      using fluorescence lifetime read-outs. The first sensor, TN-L15, consists of a
      Troponin-C fragment inserted between CFP and Citrine while the second sensor,
      called mTFP-TnC-Cit, was realized by replacing CFP in TN-L15 with monomeric Teal
      Fluorescent Protein (mTFP1). Using cytosol preparations of transiently
      transfected mammalian cells, we have measured the fluorescence decay profiles of
      these sensors at controlled concentrations of calcium using time-correlated
      single photon counting. These data were fitted to discrete exponential decay
      models using global analysis to determine the FRET efficiency, fraction of donor
      molecules undergoing FRET and calcium affinity of these sensors. We have also
      studied the decay profiles of the donor fluorescent proteins alone and determined
      the sensitivity of the donor lifetime to temperature and emission wavelength.
      Live-cell fluorescence lifetime imaging (FLIM) of HEK293T cells expressing each
      of these sensors was also undertaken. We confirmed that donor fluorescence of
      mTFP-TnC-Cit fits well to a two-component decay model, while the TN-L15 lifetime
      data was best fitted to a constrained four-component model, which was supported
      by phasor analysis of the measured lifetime data. If the constrained global
      fitting is employed, the TN-L15 sensor can provide a larger dynamic range of
      lifetime readout than the mTFP-TnC-Cit sensor but the CFP donor is significantly
      more sensitive to changes in temperature and emission wavelength compared to mTFP
      and, while the mTFP-TnC-Cit solution phase data broadly agreed with measurements
      in live cells, this was not the case for the TN-L15 sensor. Our titration
      experiment also indicates that a similar precision in determination of calcium
      concentration can be achieved with both FRET biosensors when fitting a single
      exponential donor fluorescence decay model to the fluorescence decay profiles. We
      therefore suggest that mTFP-based probes are more suitable for FLIM experiments
      than CFP-based probes.

PMID- 23152875
TI  - Effects of hydrogen peroxide on wound healing in mice in relation to oxidative
      damage.
AB  - It has been established that low concentrations of hydrogen peroxide (H(2)O(2))
      are produced in wounds and is required for optimal healing. Yet at the same time,
      there is evidence that excessive oxidative damage is correlated with poor-healing
      wounds. In this paper, we seek to determine whether topical application of
      H(2)O(2) can modulate wound healing and if its effects are related to oxidative
      damage. Using a C57BL/6 mice excision wound model, H(2)O(2) was found to enhance
      angiogenesis and wound closure at 10 mM but retarded wound closure at 166 mM. The
      delay in closure was also associated with decreased connective tissue formation,
      increased MMP-8 and persistent neutrophil infiltration. Wounding was found to
      increase oxidative lipid damage, as measured by F(2)-isoprostanes, and nitrative
      protein damage, as measured by 3-nitrotyrosine. However H(2)O(2) treatment did
      not significantly increase oxidative and nitrative damage even at concentrations
      that delay wound healing. Hence the detrimental effects of H(2)O(2) may not
      involve oxidative damage to the target molecules studied.

PMID- 23152876
TI  - High fat diet induced developmental defects in the mouse: oocyte meiotic
      aneuploidy and fetal growth retardation/brain defects.
AB  - BACKGROUND: Maternal obesity is associated with poor outcomes across the
      reproductive spectrum including infertility, increased time to pregnancy, early
      pregnancy loss, fetal loss, congenital abnormalities and neonatal conditions.
      Furthermore, the proportion of reproductive-aged woman that are obese in the
      population is increasing sharply. From current studies it is not clear if the
      origin of the reproductive complications is attributable to problems that arise
      in the oocyte or the uterine environment. METHODOLOGY/PRINCIPAL FINDINGS: We
      examined the developmental basis of the reproductive phenotypes in obese animals
      by employing a high fat diet mouse model of obesity. We analyzed very early
      embryonic and fetal phenotypes, which can be parsed into three abnormal
      developmental processes that occur in obese mothers. The first is oocyte meiotic
      aneuploidy that then leads to early embryonic loss. The second is an abnormal
      process distinct from meiotic aneuploidy that also leads to early embryonic loss.
      The third is fetal growth retardation and brain developmental abnormalities,
      which based on embryo transfer experiments are not due to the obese uterine
      environment but instead must be from a defect that arises prior to the blastocyst
      stage. CONCLUSIONS/SIGNIFICANCE: Our results suggest that reproductive
      complications in obese females are, at least in part, from oocyte maternal
      effects. This conclusion is consistent with IVF studies where the increased
      pregnancy failure rate in obese women returns to the normal rate if donor oocytes
      are used instead of autologous oocytes. We postulate that preconceptional weight
      gain adversely affects pregnancy outcomes and fetal development. In light of our
      findings, preconceptional counseling may be indicated as the preferable, earlier
      target for intervention in obese women desiring pregnancy and healthy outcomes.

PMID- 23152877
TI  - Is gene flow promoting the reversal of pleistocene divergence in the Mountain
      Chickadee (Poecile gambeli)?
AB  - The Pleistocene glacial cycles left a genetic legacy on taxa throughout the
      world; however, the persistence of genetic lineages that diverged during these
      cycles is dependent upon levels of gene flow and introgression. The consequences
      of secondary contact among taxa may reveal new insights into the history of the
      Pleistocene's genetic legacy. Here, we use phylogeographic methods, using 20
      nuclear loci from regional populations, to infer the consequences of secondary
      contact following divergence in the Mountain Chickadee (Poecile gambeli).
      Analysis of nuclear data identified two geographically-structured genetic groups,
      largely concordant with results from a previous mitochondrial DNA (mtDNA) study.
      Additionally, the estimated multilocus divergence times indicate a Pleistocene
      divergence, and are highly concordant with mtDNA. The previous mtDNA study showed
      a paucity of sympatry between clades, while nuclear patterns of gene flow show
      highly varied patterns between populations. The observed pattern of gene flow,
      from coalescent-based analyses, indicates southern populations in both clades
      exhibit little gene flow within or between clades, while northern populations are
      experiencing higher gene flow within and between clades. If this pattern were to
      persist, it is possible the historical legacy of Pleistocene divergence may be
      preserved in the southern populations only, and the northern populations would
      become a genetically diverse hybrid species.

PMID- 23152878
TI  - Structural variation and uniformity among tetraloop-receptor interactions and
      other loop-helix interactions in RNA crystal structures.
AB  - Tetraloop-receptor interactions are prevalent structural units in RNAs, and
      include the GAAA/11-nt and GNRA-minor groove interactions. In this study, we have
      compiled a set of 78 nonredundant loop-helix interactions from X-ray crystal
      structures, and examined them for the extent of their sequence and structural
      variation. Of the 78 interactions in the set, only four were classical GAAA/11-nt
      motifs, while over half (48) were GNRA-minor groove interactions. The GNRA-minor
      groove interactions were not a homogeneous set, but were divided into five
      subclasses. The most predominant subclass is characterized by two triple base
      pair interactions in the minor groove, flanked by two ribose zipper contacts.
      This geometry may be considered the "standard" GNRA-minor groove interaction,
      while the other four subclasses are alternative ways to form interfaces between a
      minor groove and tetraloop. The remaining 26 structures in the set of 78 have
      loops interacting with mostly idiosyncratic receptors. Among the entire set, a
      number of sequence-structure correlations can be identified, which may be used as
      initial hypotheses in predicting three-dimensional structures from primary
      sequences. Conversely, other sequence patterns are not predictive; for example,
      GAAA loop sequences and GG/CC receptors bind to each other with three distinct
      geometries. Finally, we observe an example of structural evolution in group II
      introns, in which loop-receptor motifs are substituted for each other while
      maintaining the larger three-dimensional geometry. Overall, the study gives a
      more complete view of RNA loop-helix interactions that exist in nature.

PMID- 23152879
TI  - Schistosoma japonicum soluble egg antigens attenuate IFN-gamma-induced MHC class
      II expression in RAW 264.7 macrophages.
AB  - Innate immune response plays the key role in initiating and guiding the immune
      response. Elucidating the innate immune related molecular events involved in the
      interaction between the parasite and the host will aid in the development of an
      effective vaccine and anti-schistosome pharmaceuticals. In this study, we
      examined the regulatory effect of Schistosoma japonicum soluble egg antigen (SEA)
      on MHC class II expression in macrophage cell line RAW 264.7. We demonstrated
      that SEA possesses the ability to down-regulate IFN-gamma-induced MHC class II
      expression in RAW 264.7 cells. The production of IL-10 and IL-6 in RAW 264.7
      cells, induced by SEA, was responsible for mediating the down-regulation of MHC
      class II. Our findings suggest that in RAW 264.7 cells (1) IFN-gamma provides a
      condition for lower concentrations of SEA to attenuate MHC class II expression;
      (2) SEA attenuated IFN-gamma-induced MHC class II expression and the IL-10 and IL
      6 production is mediated at least partly by the interaction of SEA with TLR4; and
      (3) SEA attenuated IFN-gamma-induced MHC class II expression at the
      transcriptional level.

PMID- 23152880
TI  - Should sputum smear examination be carried out at the end of the intensive phase
      and end of treatment in sputum smear negative pulmonary TB patients?
AB  - BACKGROUND: The Indian guidelines on following up sputum smear-negative Pulmonary
      tuberculosis (PTB) patients differ from the current World Health Organization
      (WHO) guidelines in that the former recommends two follow up sputum examinations
      (once at the end of intensive phase and the other at the end of treatment) while
      the latter recommends only one follow up sputum smear microscopy examination,
      which is done at the end of the intensive phase. This study was conducted to
      examine if there was any added value in performing an additional sputum smear
      examination at the end of treatment within the context of a national TB program.
      METHODS: This study was a descriptive record based review conducted in nine
      tuberculosis (TB) units in Delhi, India. All consecutive new sputum smear
      negative PTB patients registered in these nine TB units from 1(st) January 2009
      to 31(st) December 2009 were included in the study. RESULTS: Of 2567 new sputum
      smear-negative TB patients, 1973 (90%) had sputum specimens examined at the end
      of the intensive phase, of whom 36 (2%) were smear-positive: the majority (n =
      28) successfully completed treatment with either the same or a re-treatment
      regimen. At treatment completion, 1766 (85%) patients had sputum specimens
      examined, of whom 16 (0.9%) were smear-positive: all these were changed to a re
      treatment regimen. Amongst the sputum-positive patients identified as a result of
      follow up (n = 52), four were diagnosed with multi-drug resistant TB (MDR-TB),
      three of whom were detected after smear examination at the end of treatment.
      CONCLUSIONS: Given the high burden of TB in India, a 0.9% additional yield of
      smear-positive sputum smears at the end of treatment translates to 3,297 cases of
      smear-positive PTB. End-of-treatment smear is a low-yield strategy for detection
      of smear-positive TB cases, although further studies are needed to determine its
      population-level impact and cost, particularly in relation to other TB control
      interventions.

PMID- 23152881
TI  - Acupuncture induces divergent alterations of functional connectivity within
      conventional frequency bands: evidence from MEG recordings.
AB  - As an ancient Chinese healing modality which has gained increasing popularity in
      modern society, acupuncture involves stimulation with fine needles inserted into
      acupoints. Both traditional literature and clinical data indicated that
      modulation effects largely depend on specific designated acupoints. However,
      scientific representations of acupoint specificity remain controversial. In the
      present study, considering the new findings on the sustained effects of
      acupuncture and its time-varied temporal characteristics, we employed an
      electrophysiological imaging modality namely magnetoencephalography with a
      temporal resolution on the order of milliseconds. Taken into account the
      differential band-limited signal modulations induced by acupuncture, we sought to
      explore whether or not stimulation at Stomach Meridian 36 (ST36) and a nearby non
      meridian point (NAP) would evoke divergent functional connectivity alterations
      within delta, theta, alpha, beta and gamma bands. Whole-head scanning was
      performed on 28 healthy participants during an eyes-closed no-task condition both
      preceding and following acupuncture. Data analysis involved calculation of band
      limited power (BLP) followed by pair-wise BLP correlations. Further averaging was
      conducted to obtain local and remote connectivity. Statistical analyses revealed
      the increased connection degree of the left temporal cortex within delta (0.5-4
      Hz), beta (13-30 Hz) and gamma (30-48 Hz) bands following verum acupuncture.
      Moreover, we not only validated the closer linkage of the left temporal cortex
      with the prefrontal and frontal cortices, but further pinpointed that such
      patterns were more extensively distributed in the ST36 group in the delta and
      beta bands compared to the restriction only to the delta band for NAP.
      Psychophysical results for significant pain threshold elevation further confirmed
      the analgesic effect of acupuncture at ST36. In conclusion, our findings may
      provide a new perspective to lend support for the specificity of neural
      expression underlying acupuncture.

PMID- 23152882
TI  - MUC4 and MUC1 expression in adenocarcinoma of the stomach correlates with vessel
      invasion and lymph node metastasis: an immunohistochemical study of early gastric
      cancer.
AB  - We have previously reported that MUC4 expression is a poor prognostic factor in
      various carcinomas. Our previous study also showed that MUC1 expression in
      gastric cancers, including the early and advanced stages is a poor prognostic
      factor. In the present study, the expression profiles of MUC4 and MUC1 were
      examined by immunohistochemistry (IHC) using two anti-MUC4 monoclonal antibodies
      (MAbs), 8G7 and 1G8, and anti-MUC1 MAb DF3 in 104 gastrectomy specimens of early
      gastric adenocarcinoma with submucosal invasion (pT1b2), including 197
      histological subtype lesions. Before the IHC study of the human specimens, we
      evaluated the specificity of the two MAbs by Western blotting and IHC of two MUC4
      mRNA expressing gastric cancer cell lines. MAb 8G7 reacted clearly, whereas MAb
      1G8 did not show any reactivity, in either Western blotting or IHC. In the IHC of
      the gastric cancers, the expression rates of MUC4/8G7 detected by MAb 8G7,
      MUC4/1G8 detected by MAb 1G8 and MUC1/DF3 detected by MAb DF3 in well
      differentiated types (70%, 38/54; 67%, 36/54; 52%, 28/54) were significantly
      higher than those in poorly differentiated types (18%, 10/55; 36%, 20/55; 13%,
      7/55) (P<0.0001; P = 0.0021; P<0.0001), respectively. The MUC4/8G7 expression was
      related with lymphatic invasion (r = 0.304, P = 0.033). On the other hand, the
      MUC4/1G8 expression was related with lymphatic invasion (r = 0.395, P = 0.001)
      and lymph node metastasis (r = 0.296, P = 0.045). The MUC1/DF3 expression was
      related with lymphatic invasion (r = 0.357, P = 0.032) and venous invasion (r =
      0.377, P = 0.024). In conclusion, the expression of MUC4 as well as MUC1 in early
      gastric cancers is a useful marker to predict poor prognostic factors related
      with vessel invasion.

PMID- 23152883
TI  - Aggregatibacter actinomycetemcomitans GroEL protein promotes conversion of human
      CD4+ T cells into IFNgamma IL10 producing Tbet+ Th1 cells.
AB  - One of the heat shock family protein (Hsp) expressing bacteria is the gram
      negative, periodontal pathogen Aggregatibacter actinomycetemcomitans (Aa). A.
      actinomycetemcomitans' Hsp is a 64-kDa GroEL-protein, which has been shown to
      influence the host cells. In this study we used recombinant A.
      actinomycetemcomitans GroEL (rAaGroEL) protein as a model antigen to study GroEL
      mediated T cell immune response. Human peripheral mononuclear cells (PBMCs), when
      stimulated with recombinant rAaGroEL, expressed early activation marker CD69 and
      IL-2R (CD25). CD25 and CD69 expressions were higher in CD4+ T cells compared to
      CD8+ T cells. rAaGroEL-responding CD4+ T cells expressed IL-10, IFNgamma and
      TNFalpha cytokines. Interestingly, there were also IL-10 and IFNgamma double
      cytokine producing CD4+ T cells. Additionally, IFNgamma expressing CD4+ T cells
      were also T-bet positive. Altogether the results suggest that rAaGroEL protein
      affects CD4+ T cells to differentiate into IFNgamma IL10-secreting T-bet+ Th1
      cells.

PMID- 23152884
TI  - Modest elevation in BNP in asymptomatic hypertensive patients reflects sub
      clinical cardiac remodeling, inflammation and extracellular matrix changes.
AB  - In asymptomatic subjects B-type natriuretic peptide (BNP) is associated with
      adverse cardiovascular outcomes even at levels well below contemporary thresholds
      used for the diagnosis of heart failure. The mechanisms behind these observations
      are unclear. We examined the hypothesis that in an asymptomatic hypertensive
      population BNP would be associated with sub-clinical evidence of cardiac
      remodeling, inflammation and extracellular matrix (ECM) alterations. We performed
      transthoracic echocardiography and sampled coronary sinus (CS) and peripheral
      serum from patients with low (n = 14) and high BNP (n = 27). Peripheral BNP was
      closely associated with CS levels (r = 0.92, p<0.001). CS BNP correlated
      significantly with CS levels of markers of collagen type I and III turnover
      including: PINP (r = 0.44, p = 0.008), CITP (r = 0.35, p = 0.03) and PIIINP (r =
      0.35, p = 0.001), and with CS levels of inflammatory cytokines including: TNF
      alpha (r = 0.49, p = 0.002), IL-6 (r = 0.35, p = 0.04), and IL-8 (r = 0.54,
      p<0.001). The high BNP group had greater CS expression of fibro-inflammatory
      biomarkers including: CITP (3.8+/-0.7 versus 5.1+/-1.9, p = 0.007), TNF-alpha
      (3.2+/-0.5 versus 3.7+/-1.1, p = 003), IL-6 (1.9+/-1.3 versus 3.4+/-2.7, p =
      0.02) and hsCRP (1.2+/-1.1 versus 2.4+/-1.1, p = 0.04), and greater left
      ventricular mass index (97+/-20 versus 118+/-26 g/m(2), p = 0.03) and left atrial
      volume index (18+/-2 versus 21+/-4, p = 0.008). Our data provide insight into the
      mechanisms behind the observed negative prognostic impact of modest elevations in
      BNP and suggest that in an asymptomatic hypertensive cohort a peripheral BNP
      measurement may be a useful marker of an early, sub-clinical pathological process
      characterized by cardiac remodeling, inflammation and ECM alterations.

PMID- 23152885
TI  - The effect of PRMT1-mediated arginine methylation on the subcellular
      localization, stress granules, and detergent-insoluble aggregates of FUS/TLS.
AB  - Fused in sarcoma/translocated in liposarcoma (FUS/TLS) is one of causative genes
      for familial amyotrophic lateral sclerosis (ALS). In order to identify binding
      partners for FUS/TLS, we performed a yeast two-hybrid screening and found that
      protein arginine methyltransferase 1 (PRMT1) is one of binding partners primarily
      in the nucleus. In vitro and in vivo methylation assays showed that FUS/TLS could
      be methylated by PRMT1. The modulation of arginine methylation levels by a
      general methyltransferase inhibitor or conditional over-expression of PRMT1
      altered slightly the nucleus-cytoplasmic ratio of FUS/TLS in cell fractionation
      assays. Although co-localized primarily in the nucleus in normal condition,
      FUS/TLS and PRMT1 were partially recruited to the cytoplasmic granules under
      oxidative stress, which were merged with stress granules (SGs) markers in SH-SY5Y
      cell. C-terminal truncated form of FUS/TLS (FUS-dC), which lacks C-terminal
      nuclear localization signal (NLS), formed cytoplasmic inclusions like ALS-linked
      FUS mutants and was partially co-localized with PRMT1. Furthermore, conditional
      over-expression of PRMT1 reduced the FUS-dC-mediated SGs formation and the
      detergent-insoluble aggregates in HEK293 cells. These findings indicate that
      PRMT1-mediated arginine methylation could be implicated in the nucleus
      cytoplasmic shuttling of FUS/TLS and in the SGs formation and the detergent
      insoluble inclusions of ALS-linked FUS/TLS mutants.

PMID- 23152886
TI  - Quercetin suppresses drug-resistant spheres via the p38 MAPK-Hsp27 apoptotic
      pathway in oral cancer cells.
AB  - BACKGROUND: Treatment failure in oral squamous cell carcinoma (OSCC) leading to
      local recurrence(s) and metastases is mainly due to drug resistance. Cancer stem
      cells (CSCs) are thought be responsible for the development of drug resistance.
      However, the correlations between CSCs, drug resistance, and new strategy against
      drug resistance in OSCC remain elusive. METHODS: A drug-resistant sphere (DRSP)
      model was generated by using a nonadhesive culture system to induce drug
      resistant cells from SCC25 oral cancer cells. A comparative analysis was
      performed between the parent control cells and DRSPs with a related treatment
      strategy focusing on the expression of epithelial-mesenchymal transition (EMT)
      associated markers, drug-resistance-related genes, and CSC properties in vitro,
      as well as tumorigenicity and the regimen for tumor regression in vivo. RESULTS:
      Our data show the presence of a phenomenon of EMT with gradual cellular
      transition from an epithelioid to mesenchymal-like spheroid morphology during
      induction of drug resistance. The characterization of DRSPs revealed the
      upregulation of the drug-resistance-related genes ABCG2 and MDR-1 and of CSC
      representative markers, suggesting that DRSPs have greater resistance to
      cisplatin (Cis) and stronger CSC properties compared with the control. Moreover,
      overexpression of phosphorylated heat-shock protein 27 (p-Hsp27) via the
      activation of p38 MAPK signaling was observed in DRSPs. Knockdown of Hsp27
      decreased Cis resistance and induced apoptosis in DRSPs. Furthermore, an
      inhibitor of Hsp27, quercetin (Qu), suppressed p-Hsp27 expression, with
      alterations of the EMT signature, leading to the promotion of apoptosis in DRSPs.
      A xenographic study also confirmed the increase of tumorigenicity in DRSPs. The
      combination of Qu and Cis can reduce tumor growth and decrease drug resistance in
      OSCC. CONCLUSIONS: The p38 MAPK-Hsp27 axis plays an important role in CSCs
      mediated drug resistance in OSCC. Targeting this axis using Qu combined with Cis
      may be a treatment strategy to improve prognosis in patients with OSCC.

PMID- 23152887
TI  - Fluorescent In Situ hybridization: a new tool for the direct identification and
      detection of F. psychrophilum.
AB  - F. psychrophilum is the causative agent of Bacterial Cold Water Disease (BCW) and
      Rainbow Trout Fry Syndrome (RTFS). To date, diagnosis relies mainly on direct
      microscopy or cultural methods. Direct microscopy is fast but not very reliable,
      whereas cultural methods are reliable but time-consuming and labor-intensive. So
      far fluorescent in situ hybridization (FISH) has not been used in the diagnosis
      of flavobacteriosis but it has the potential to rapidly and specifically detect
      F. psychrophilum in infected tissues. Outbreaks in fish farms, caused by
      pathogenic strains of Flavobacterium species, are increasingly frequent and there
      is a need for reliable and cost-effective techniques to rapidly diagnose
      flavobacterioses. This study is aimed at developing a FISH that could be used for
      the diagnosis of F. psychrophilum infections in fish. We constructed a generic
      probe for the genus Flavobacterium ("Pan-Flavo") and two specific probes
      targeting F. psychrophilum based on 16S rRNA gene sequences. We tested their
      specificity and sensitivity on pure cultures of different Flavobacterium and
      other aquatic bacterial species. After assessing their sensitivity and
      specificity, we established their limit of detection and tested the probes on
      infected fresh tissues (spleen and skin) and on paraffin-embedded tissues. The
      results showed high sensitivity and specificity of the probes (100% and 91% for
      the Pan-Flavo probe and 100% and 97% for the F. psychrophilum probe,
      respectively). FISH was able to detect F. psychrophilum in infected fish tissues,
      thus the findings from this study indicate this technique is suitable as a fast
      and reliable method for the detection of Flavobacterium spp. and F.
      psychrophilum.

PMID- 23152888
TI  - The ABCA1 gene R230C variant is associated with decreased risk of premature
      coronary artery disease: the genetics of atherosclerotic disease (GEA) study.
AB  - BACKGROUND: ABCA1 genetic variation is known to play a role in HDL-C levels and
      various studies have also implicated ABCA1 variation in cardiovascular risk. The
      functional ABCA1/R230C variant is frequent in the Mexican population and has been
      consistently associated with low HDL-C concentrations. Although it has been
      associated with other cardiovascular risk factors such as obesity and type 2
      diabetes mellitus, it is not known whether it is associated with coronary artery
      disease (CAD). AIM: The purpose of the study was to analyze whether the
      ABCA1/R230C variant is associated with premature CAD in a case-control
      association study (GEA or Genetics of Atherosclerotic Disease), and to explore
      whether BMI modulates the effect of the C230 allele on other metabolic traits
      using a population-based design. RESULTS: The C230 allele was significantly
      associated with both lower HDL-C levels and a lower risk of premature CAD as
      compared to controls (OR = 0.566; P(add) = 1.499*10(-5)). In addition, BMI
      modulated the effect of R230C on body fat distribution, as the correlation
      between BMI and visceral to subcutaneous adipose tissue (a metric of the
      propensity to store fat viscerally as compared to subcutaneously) was negative in
      RR homozygous individuals, but positive in premenopausal women bearing the C230
      allele, with a statistically significant interaction (P = 0.005). BMI-R230C
      interaction was also significant for triglyceride levels in women regardless of
      their menopausal status (P = 0.036). CONCLUSION: This is the first study
      assessing the effect of the R230C/ABCA1 variant in remature CAD. C230 was
      associated with both decreased HDL-C levels and a lower risk of premature CAD,
      and gender-specific BMI-R230C interactions were observed for different metabolic
      traits. These interactions may help explain inconsistencies in associations, and
      underscore the need to further analyze interactions of this functional and
      frequent variant with diet, exercise and other environmental factors.

PMID- 23152889
TI  - MicroRNA 142-3p mediates post-transcriptional regulation of D1 dopamine receptor
      expression.
AB  - The D1 dopamine receptor subtype is expressed in the brain, kidney and
      lymphocytes. D1 receptor function has been extensively studied and the receptor
      has been shown to modulate a wide range of physiological functions and behaviors.
      The expression of D1 receptor is known to change during development, disease
      states and chronic treatment; however, the molecular mechanisms that mediate the
      changes in D1 receptor expression under these circumstances are not well
      understood. While previous studies have identified extracellular factors and
      signaling mechanisms regulating the transcription of D1 receptor gene, very
      little is known about other regulatory mechanisms that modulate the expression of
      the D1 receptor gene. Here we report that the D1 receptor is post
      transcriptionally regulated during postnatal mouse brain development and in the
      mouse CAD catecholaminergic neuronal cell line. We demonstrate that this post
      transcriptional regulation is mediated by a molecular mechanism involving
      noncoding RNA. We show that the 1277 bp 3'untranslated region of D1 receptor mRNA
      is necessary and sufficient for mediating the post-transcriptional regulation.
      Using deletion and site-directed mutagenesis approaches, we show that the D1
      receptor post-transcriptional regulation is specifically mediated by microRNA miR
      142-3p interacting with a single consensus binding site in the 1277 bp
      3'untranslated region of D1 receptor mRNA. Inhibiting endogenous miR-142-3p in
      CAD cells increased endogenous D1 receptor protein expression levels. The
      increase in D1 receptor protein levels was biologically significant as it
      resulted in enhanced D1 receptor-mediated signaling, determined by measuring the
      activation of both, adenylate cyclase and, the dopamine- and cAMP-regulated
      phosphoprotein, DARPP-32. We also show that there is an inverse correlation
      between miR-142-3p levels and D1 receptor protein expression in the mouse brain
      during postnatal development. This is the first study to demonstrate that the
      post-transcriptional regulation of D1 receptor expression is mediated by microRNA
      induced translational suppression.

PMID- 23152890
TI  - Pharmacologic boosting of atazanavir in maintenance HIV-1 therapy: the COREYA
      propensity-score adjusted study.
AB  - BACKGROUND: Among HIV-1 infected patients who achieved virologic suppression, the
      use of atazanavir without pharmacologic boosting is debated. We evaluated the
      efficacy and tolerance of maintenance therapy with unboosted atazanavir in
      clinical practice. METHODS AND RESULTS: This multicenter retrospective cohort
      study evaluated the efficacy of switching HIV-1-infected patients controlled on
      triple therapy to unboosted (ATV(0), n = 98) versus ritonavir-boosted atazanavir
      (ATV/r, n = 254) +2 nucleos(t)ide reverse transcriptase inhibitors. The primary
      endpoint was time to virologic failure (VF, >200 copies/mL). ATV groups were
      compared controlling for potential confounding bias by inverse probability
      weighted Cox analysis and propensity-score matching. Overall and adjusted VF
      rates were similar for both strategies. Both strategies improved dyslipidemia and
      creatininemia, with less jaundice in the ATV(0) group. CONCLUSION: In previously
      well-suppressed patients, within an observational cohort setting, ATV(0)-based
      triple-therapy appeared as effective as ATV/r- based triple-therapy to maintain
      virologic suppression, even if co-administered with TDF, but was better
      tolerated.

PMID- 23152891
TI  - A differential genome-wide transcriptome analysis: impact of cellular copper on
      complex biological processes like aging and development.
AB  - The regulation of cellular copper homeostasis is crucial in biology. Impairments
      lead to severe dysfunctions and are known to affect aging and development.
      Previously, a loss-of-function mutation in the gene encoding the copper-sensing
      and copper-regulated transcription factor GRISEA of the filamentous fungus
      Podospora anserina was reported to lead to cellular copper depletion and a
      pleiotropic phenotype with hypopigmentation of the mycelium and the ascospores,
      affected fertility and increased lifespan by approximately 60% when compared to
      the wild type. This phenotype is linked to a switch from a copper-dependent
      standard to an alternative respiration leading to both a reduced generation of
      reactive oxygen species (ROS) and of adenosine triphosphate (ATP). We performed a
      genome-wide comparative transcriptome analysis of a wild-type strain and the
      copper-depleted grisea mutant. We unambiguously assigned 9,700 sequences of the
      transcriptome in both strains to the more than 10,600 predicted and annotated
      open reading frames of the P. anserina genome indicating 90% coverage of the
      transcriptome. 4,752 of the transcripts differed significantly in abundance with
      1,156 transcripts differing at least 3-fold. Selected genes were investigated by
      qRT-PCR analyses. Apart from this general characterization we analyzed the data
      with special emphasis on molecular pathways related to the grisea mutation taking
      advantage of the available complete genomic sequence of P. anserina. This
      analysis verified but also corrected conclusions from earlier data obtained by
      single gene analysis, identified new candidates of factors as part of the
      cellular copper homeostasis system including target genes of transcription factor
      GRISEA, and provides a rich reference source of quantitative data for further in
      detail investigations. Overall, the present study demonstrates the importance of
      systems biology approaches also in cases were mutations in single genes are
      analyzed to explain the underlying mechanisms controlling complex biological
      processes like aging and development.

PMID- 23152892
TI  - The microtubule-associated protein ASPM regulates spindle assembly and meiotic
      progression in mouse oocytes.
AB  - The microtubule-associated protein ASPM (abnormal spindle-like microcephaly
      associated) plays an important role in spindle organization and cell division in
      mitosis and meiosis in lower animals, but its function in mouse oocyte meiosis
      has not been investigated. In this study, we characterized the localization and
      expression dynamics of ASPM during mouse oocyte meiotic maturation and analyzed
      the effects of the downregulation of ASPM expression on meiotic spindle assembly
      and meiotic progression. Immunofluorescence analysis showed that ASPM localized
      to the entire spindle at metaphase I (MI) and metaphase II (MII), colocalizing
      with the spindle microtubule protein acetylated tubulin (Ac-tubulin). In taxol
      treated oocytes, ASPM colocalized with Ac-tubulin on the excessively polymerized
      microtubule fibers of enlarged spindles and the numerous asters in the cytoplasm.
      Nocodazole treatment induced the gradual disassembly of microtubule fibers,
      during which ASPM remained colocalized with the dynamic Ac-tubulin. The
      downregulation of ASPM expression by a gene-specific morpholino resulted in an
      abnormal meiotic spindle and inhibited meiotic progression; most of the treated
      oocytes were blocked in the MI stage with elongated meiotic spindles.
      Furthermore, coimmunoprecipitation combined with mass spectrometry and western
      blot analysis revealed that ASPM interacted with calmodulin in MI oocytes and
      that these proteins colocalized at the spindle. Our results provide strong
      evidence that ASPM plays a critical role in meiotic spindle assembly and meiotic
      progression in mouse oocytes.

PMID- 23152893
TI  - Inhibition of 5'-UTR RNA conformational switching in HIV-1 using antisense PNAs.
AB  - BACKGROUND: The genome of retroviruses, including HIV-1, is packaged as two
      homologous (+) strand RNA molecules, noncovalently associated close to their 5'
      end in a region called dimer linkage structure (DLS). Retroviral HIV-1 genomic
      RNAs dimerize through complex interactions between dimerization initiation sites
      (DIS) within the (5'-UTR). Dimer formation is prevented by so calledLong Distance
      Interaction (LDI) conformation, whereas Branched Multiple Hairpin (BMH)
      conformation leads to spontaneous dimerization. METHODS AND RESULTS: We evaluated
      the role of SL1 (DIS), PolyA Hairpin signal and a long distance U5-AUG
      interaction by in-vitro dimerization, conformer assay and coupled dimerization
      and template-switching assays using antisense PNAs. Our data suggests evidence
      that PNAs targeted against SL1 produced severe inhibitory effect on dimerization
      and template-switching processes while PNAs targeted against U5 region do not
      show significant effect on dimerization and template switching, while PNAs
      targeted against AUG region showed strong inhibition of dimerization and template
      switching processes. CONCLUSIONS: Our results demonstrate that PNA can be used
      successfully as an antisense to inhibit dimerization and template switching
      process in HIV -1 and both of the processes are closely linked to each other.
      Different PNA oligomers have ability of switching between two thermodynamically
      stable forms. PNA targeted against DIS and SL1 switch, LDI conformer to more
      dimerization friendly BMH form. PNAs targeted against PolyA haipin configuration
      did not show a significant change in dimerization and template switching process.
      The PNA oligomer directed against the AUG strand of U5-AUG duplex structure also
      showed a significant reduction in RNA dimerization as well as template- switching
      efficiency.The antisense PNA oligomers can be used to regulate the shift in the
      LDI/BMH equilibrium.

PMID- 23152894
TI  - Differential effects of visual feedback on subjective visual vertical accuracy
      and precision.
AB  - The brain constructs an internal estimate of the gravitational vertical by
      integrating multiple sensory signals. In darkness, systematic head-roll dependent
      errors in verticality estimates, as measured by the subjective visual vertical
      (SVV), occur. We hypothesized that visual feedback after each trial results in
      increased accuracy, as physiological adjustment errors (A-/E-effect) are likely
      based on central computational mechanisms and investigated whether such
      improvements were related to adaptational shifts of perceived vertical or to a
      higher cognitive strategy. We asked 12 healthy human subjects to adjust a
      luminous arrow to vertical in various head-roll positions (0 to 120deg right-ear
      down, 15deg steps). After each adjustment visual feedback was provided (lights
      on, display of previous adjustment and of an earth-vertical cross). Control
      trials consisted of SVV adjustments without feedback. At head-roll angles with
      the largest A-effect (90, 105, and 120deg), errors were reduced significantly
      (p<0.001) by visual feedback, i.e. roll under-compensation decreased, while
      precision of SVV was not significantly (p>0.05) influenced. In seven subjects an
      additional session with two consecutive blocks (first with, then without visual
      feedback) was completed at 90, 105 and 120deg head-roll. In these positions the
      error-reduction by the previous visual feedback block remained significant over
      the consecutive 18-24 min (post-feedback block), i.e., was still significantly
      (p<0.002) different from the control trials. Eleven out of 12 subjects reported
      having consciously added a bias to their perceived vertical based on visual
      feedback in order to minimize errors. We conclude that improvements of SVV
      accuracy by visual feedback, which remained effective after removal of feedback
      for >=18 min, rather resulted from a cognitive strategy than by adapting the
      internal estimate of the gravitational vertical. The mechanisms behind the SVV
      therefore, remained stable, which is also supported by the fact that SVV
      precision - depending mostly on otolith input - was not affected by visual
      feedback.

PMID- 23152895
TI  - 1,25-Dihydroxyvitamin D3 promotes a sustained LPS-induced NF-kappaB-dependent
      expression of CD55 in human monocytic THP-1 cells.
AB  - The vitamin D3 system imposes immunosuppressive effects on monocytic cells, in
      part, by inhibiting NF-kappaB-dependent expression of proinflammatory mediators.
      CD55, a cell surface complement regulatory protein that promotes protective and
      anti-inflammatory properties, is reportedly an NF-kappaB target gene transiently
      induced in monocytic cells by the bacterial endotoxin LPS. CD55 is elevated on
      white cells in women experiencing preterm labor (a pathophysiology commonly
      associated with bacterial infection) and failure to maintain CD55 was associated
      with subsequent preterm delivery. We examined the influence of vitamin D3
      signaling on LPS-induced expression of CD55 in human monocytic THP-1 cells using
      quantitative PCR, immunoblot, immunohistochemistry, and NF-kappaB activation
      pathway inhibitors. Non-NF-kappaB targets CD14 and CD11b, which modulate
      bacterial surveillance and eradication, respectively, were also examined. LPS
      produced a rapid transient 1.6-fold increase in CD55 mRNA. 1,25-D3 alone did not
      affect CD55 mRNA expression within the first 48 h. However, in 1,25-D3 pretreated
      cells, LPS produced a >4-fold immediate and sustained increase in CD55 mRNA and
      protein expression, which was blocked by NF-kappaB inhibitors. Our results
      unexpectedly suggest that vitamin D3 signaling may promote an anti-inflammatory
      response through an NF-kappaB-dependent increase in CD55 expression. As expected,
      LPS or 1,25-D3 alone led to sustained increases in CD14 and CD11b expression. In
      1,25-D3 pretreated cells, LPS differentially regulated protein expression - CD14
      (21-fold increase) and CD11b (a transient 2-fold decrease) - principally at the
      posttranscriptional level. The coordinated temporal expression of CD55, CD14 and
      CD11b would contribute to an anti-inflammatory response by providing protection
      against complement-mediated cell lysis during pathogen recognition and
      eradication. Overall, the vitamin D3 system may play a role coordinating an anti
      inflammatory response pattern of the host complement immune system. This may be
      particularly important when considering the high rates of preterm births in
      blacks, a population that exhibits reduced circulating vitamin D3 levels.

PMID- 23152896
TI  - A Baculovirus immediate-early gene, ie1, promoter drives efficient expression of
      a transgene in both Drosophila melanogaster and Bombyx mori.
AB  - Many promoters have been used to drive expression of heterologous transgenes in
      insects. One major obstacle in the study of non-model insects is the dearth of
      useful promoters for analysis of gene function. Here, we investigated whether the
      promoter of the immediate-early gene, ie1, from the Bombyx mori
      nucleopolyhedrovirus (BmNPV) could be used to drive efficient transgene
      expression in a wide variety of insects. We used a piggyBac-based vector with a
      3xP3-DsRed transformation marker to generate a reporter construct; this construct
      was used to determine the expression patterns driven by the BmNPV ie1 promoter;
      we performed a detailed investigation of the promoter in transgene expression
      pattern in Drosophila melanogaster and in B. mori. Drosophila and Bombyx belong
      to different insect orders (Diptera and Lepidoptera, respectively); however, and
      to our surprise, ie1 promoter-driven expression was evident in several tissues
      (e.g., prothoracic gland, midgut, and tracheole) in both insects. Furthermore, in
      both species, the ie1 promoter drove expression of the reporter gene from a
      relatively early embryonic stage, and strong ubiquitous ie1 promoter-driven
      expression continued throughout the larval, pupal, and adult stages by surface
      observation. Therefore, we suggest that the ie1 promoter can be used as an
      efficient expression driver in a diverse range of insect species.

PMID- 23152897
TI  - Promotion of human early embryonic development and blastocyst outgrowth in vitro
      using autocrine/paracrine growth factors.
AB  - Studies using animal models demonstrated the importance of autocrine/paracrine
      factors secreted by preimplantation embryos and reproductive tracts for embryonic
      development and implantation. Although in vitro fertilization-embryo transfer
      (IVF-ET) is an established procedure, there is no evidence that present culture
      conditions are optimal for human early embryonic development. In this study, key
      polypeptide ligands known to be important for early embryonic development in
      animal models were tested for their ability to improve human early embryo
      development and blastocyst outgrowth in vitro. We confirmed the expression of key
      ligand/receptor pairs in cleavage embryos derived from discarded human tri
      pronuclear zygotes and in human endometrium. Combined treatment with key
      embryonic growth factors (brain-derived neurotrophic factor, colony-stimulating
      factor, epidermal growth factor, granulocyte macrophage colony-stimulating
      factor, insulin-like growth factor-1, glial cell-line derived neurotrophic
      factor, and artemin) in serum-free media promoted >2.5-fold the development of
      tri-pronuclear zygotes to blastocysts. For normally fertilized embryos, day 3
      surplus embryos cultured individually with the key growth factors showed >3-fold
      increases in the development of 6-8 cell stage embryos to blastocysts and >7-fold
      increase in the proportion of high quality blastocysts based on Gardner's
      criteria. Growth factor treatment also led to a 2-fold promotion of blastocyst
      outgrowth in vitro when day 7 surplus hatching blastocysts were used. When failed
      to-be-fertilized oocytes were used to perform somatic cell nuclear transfer
      (SCNT) using fibroblasts as donor karyoplasts, inclusion of growth factors
      increased the progression of reconstructed SCNT embryos to >4-cell stage embryos.
      Growth factor supplementation of serum-free cultures could promote optimal early
      embryonic development and implantation in IVF-ET and SCNT procedures. This
      approach is valuable for infertility treatment and future derivation of patient
      specific embryonic stem cells.

PMID- 23152898
TI  - Proteomic analysis of the increased stress tolerance of saccharomyces cerevisiae
      encapsulated in liquid core alginate-chitosan capsules.
AB  - Saccharomyces cerevisiae CBS8066 encapsulated in semi-permeable alginate or
      alginate-chitosan liquid core capsules have been shown to have an enhanced
      tolerance towards complex dilute-acid lignocellulose hydrolysates and the
      lignocellulose-derived inhibitor furfural, as well as towards high temperatures.
      The underlying molecular reasons for these effects have however not been
      elucidated. In this study we have investigated the response of the encapsulation
      on the proteome level in the yeast cells, in comparison with cells grown freely
      in suspension under otherwise similar conditions. The proteomic analysis was
      performed on whole cell protein extracts using nLC-MS/MS with TMT(r) labelling
      and 2-D DIGE. 842 and 52 proteins were identified using each method,
      respectively. The abundances of 213 proteins were significantly different between
      encapsulated and suspended cells, with good correlation between the fold change
      ratios obtained by the two methods for proteins identified in both. Encapsulation
      of the yeast caused an up-regulation of glucose-repressed proteins and of both
      general and starvation-specific stress responses, such as the trehalose
      biosynthesis pathway, and down-regulation of proteins linked to growth and
      protein synthesis. The encapsulation leads to a lack of nutrients for cells close
      to the core of the capsule due to mass transfer limitations. The triggering of
      the stress response may be beneficial for the cells in certain conditions, for
      example leading to the increased tolerance towards high temperatures and certain
      inhibitors.

PMID- 23152899
TI  - How does our motor system determine its learning rate?
AB  - Motor learning is driven by movement errors. The speed of learning can be
      quantified by the learning rate, which is the proportion of an error that is
      corrected for in the planning of the next movement. Previous studies have shown
      that the learning rate depends on the reliability of the error signal and on the
      uncertainty of the motor system's own state. These dependences are in agreement
      with the predictions of the Kalman filter, which is a state estimator that can be
      used to determine the optimal learning rate for each movement such that the
      expected movement error is minimized. Here we test whether not only the average
      behaviour is optimal, as the previous studies showed, but if the learning rate is
      chosen optimally in every individual movement. Subjects made repeated movements
      to visual targets with their unseen hand. They received visual feedback about
      their endpoint error immediately after each movement. The reliability of these
      error-signals was varied across three conditions. The results are inconsistent
      with the predictions of the Kalman filter because correction for large errors in
      the beginning of a series of movements to a fixed target was not as fast as
      predicted and the learning rates for the extent and the direction of the
      movements did not differ in the way predicted by the Kalman filter. Instead, a
      simpler model that uses the same learning rate for all movements with the same
      error-signal reliability can explain the data. We conclude that our brain does
      not apply state estimation to determine the optimal planning correction for every
      individual movement, but it employs a simpler strategy of using a fixed learning
      rate for all movements with the same level of error-signal reliability.

PMID- 23152900
TI  - Evidence of adaptive evolutionary divergence during biological invasion.
AB  - Rapid phenotypic diversification during biological invasions can either arise by
      adaptation to alternative environments or by adaptive phenotypic plasticity.
      Where experimental evidence for adaptive plasticity is common, support for
      evolutionary diversification is rare. Here, we performed a controlled laboratory
      experiment using full-sib crosses between ecologically divergent threespine
      stickleback populations to test for a genetic basis of adaptation. Our
      populations are from two very different habitats, lake and stream, of a recently
      invaded range in Switzerland and differ in ecologically relevant morphological
      traits. We found that in a lake-like food treatment lake fish grow faster than
      stream fish, resembling the difference among wild type individuals. In contrast,
      in a stream-like food treatment individuals from both populations grow similarly.
      Our experimental data suggest that genetically determined diversification has
      occurred within less than 140 years after the arrival of stickleback in our
      studied region.

PMID- 23152901
TI  - Molecular markers allow to remove introgressed genetic background: a simulation
      study.
AB  - The maintenance of genetically differentiated populations can be important for
      several reasons (whether for wild species or domestic breeds of economic
      interest). When those populations are introgressed by foreign individuals,
      methods to eliminate the exogenous alleles can be implemented to recover the
      native genetic background. This study used computer simulations to explore the
      usefulness of several molecular based diagnostic approaches to recover of a
      native population after suffering an introgression event where some exogenous
      alleles were admixed for a few generations. To remove the exogenous alleles,
      different types of molecular markers were used in order to decide which of the
      available individuals contributed descendants to next generation and their number
      of offspring. Recovery was most efficient using diagnostic markers (i.e., with
      private alleles) and least efficient when using alleles present in both native
      and exogenous populations at different frequencies. The increased inbreeding was
      a side-effect of the management strategy. Both values (% of native alleles and
      inbreeding) were largely dependent on the amount of exogenous individuals
      entering the population and the number of generations of admixture that occurred
      prior to management.

PMID- 23152902
TI  - Implementation of web-based respondent-driven sampling among men who have sex
      with men in Vietnam.
AB  - OBJECTIVE: Lack of representative data about hidden groups, like men who have sex
      with men (MSM), hinders an evidence-based response to the HIV epidemics.
      Respondent-driven sampling (RDS) was developed to overcome sampling challenges in
      studies of populations like MSM for which sampling frames are absent. Internet
      based RDS (webRDS) can potentially circumvent limitations of the original RDS
      method. We aimed to implement and evaluate webRDS among a hidden population.
      METHODS AND DESIGN: This cross-sectional study took place 18 February to 12
      April, 2011 among MSM in Vietnam. Inclusion criteria were men, aged 18 and above,
      who had ever had sex with another man and were living in Vietnam. Participants
      were invited by an MSM friend, logged in, and answered a survey. Participants
      could recruit up to four MSM friends. We evaluated the system by its success in
      generating sustained recruitment and the degree to which the sample compositions
      stabilized with increasing sample size. RESULTS: Twenty starting participants
      generated 676 participants over 24 recruitment waves. Analyses did not show
      evidence of bias due to ineligible participation. Estimated mean age was 22 years
      and 82% came from the two large metropolitan areas. 32 out of 63 provinces were
      represented. The median number of sexual partners during the last six months was
      two. The sample composition stabilized well for 16 out of 17 variables.
      CONCLUSION: Results indicate that webRDS could be implemented at a low cost among
      Internet-using MSM in Vietnam. WebRDS may be a promising method for sampling of
      Internet-using MSM and other hidden groups.

PMID- 23152903
TI  - HDAC6 regulates epidermal growth factor receptor (EGFR) endocytic trafficking and
      degradation in renal epithelial cells.
AB  - We present for the first time that histone deacetylase 6 (HDAC6) regulates EGFR
      degradation and trafficking along microtubules in Pkd1 mutant renal epithelial
      cells. HDAC6, the microtubule-associated alpha-tubulin deacetylase, demonstrates
      increased expression and activity in Pkd1 mutant mouse embryonic kidney cells.
      Targeting HDAC6 with a general HDAC inhibitor, trichostatin (TSA), or a specific
      HDAC6 inhibitor, tubacin, increased the acetylation of alpha-tubulin and
      downregulated the expression of EGFR in Pkd1 mutant renal epithelial cells. HDAC6
      was co-localized with EGF induced endocytic EGFR and endosomes, respectively.
      Inhibition of the activity of HDAC6 accelerated the trafficking of EGFR from
      early endosomes to late endosomes along the microtubules. Without EGF stimulation
      EGFR was randomly distributed while after stimulation with EGF for 30 min, EGFR
      was accumulated around alpha-tubulin labeled microtubule bundles. These data
      suggested that the Pkd1 mutation induced upregulation of HDAC6 might act to slow
      the trafficking of EGFR from early endosomes to late endosomes along the
      microtubules for degradation through deacetylating alpha-tubulin. In addition,
      inhibition of HDAC activity decreased the phosphorylation of ERK1/2, the
      downstream target of EGFR axis, and normalized EGFR localization from apical to
      basolateral in Pkd1 knockout mouse kidneys. Thus, targeting HDAC6 to downregulate
      EGFR activity may provide a potential therapeutic approach to treat polycystic
      kidney disease.

PMID- 23152904
TI  - Complement receptor 1 variants confer protection from severe malaria in Odisha,
      India.
AB  - BACKGROUND: In Plasmodium falciparum infection, complement receptor-1 (CR1) on
      erythrocyte's surface and ABO blood group play important roles in formation of
      rosettes which are presumed to be contributory in the pathogenesis of severe
      malaria. Although several studies have attempted to determine the association of
      CR1 polymorphisms with severe malaria, observations remain inconsistent.
      Therefore, a case control study and meta-analysis was performed to address this
      issue. METHODS: Common CR1 polymorphisms (intron 27 and exon 22) and blood group
      were typed in 353 cases of severe malaria (SM) [97 cerebral malaria (CM), 129
      multi-organ dysfunction (MOD), 127 non-cerebral severe malaria (NCSM)], 141 un
      complicated malaria and 100 healthy controls from an endemic region of Odisha,
      India. Relevant publications for meta-analysis were searched from the database.
      RESULTS: The homozygous polymorphisms of CR1 intron 27 and exon 22 (TT and GG)
      and alleles (T and G) that are associated with low expression of CR1 on red blood
      cells, conferred significant protection against CM, MOD and malaria deaths.
      Combined analysis showed significant association of blood group B/intron 27
      AA/exon 22-AA with susceptibility to SM (CM and MOD). Meta-analysis revealed that
      the CR1 exon 22 low expression polymorphism is significantly associated with
      protection against severe malaria. CONCLUSIONS: The results of the present study
      demonstrate that common CR1 variants significantly protect against severe malaria
      in an endemic area.

PMID- 23152905
TI  - The plant-derived glucocorticoid receptor agonist Endiandrin A acts as co
      stimulator of colonic epithelial sodium channels (ENaC) via SGK-1 and MAPKs.
AB  - In a search for secondary plant compounds that bind to the glucocorticoid
      receptor (GR), the cyclobutane lignan endiandrin A was discovered from the
      rainforest tree Endiandra anthropophagorum Domin. Our present study aims to
      characterize the effect of endiandrin A on GR-dependent induction of colonic
      sodium transport. The effect of endiandrin A was analyzed in GR-expressing
      colonic HT-29/B6 cells (HT-29/B6-GR). GR transactivation and subcellular
      localization were investigated by reporter gene assay and immunofluorescence.
      Epithelial sodium channel (ENaC) was analyzed by qRT-PCR and by measuring
      amiloride-sensitive short-circuit current (I(sc)) in Ussing chambers. Endiandrin
      A (End A) has been identified as GR receptor binder. However, it did not cause
      significant GR transactivation as pGRE-luciferase activity was only 7% of that of
      the maximum effect of dexamethasone. Interestingly, endiandrin A had a
      significant impact on dexamethasone-dependent sodium absorption in cells co
      exposed to tumor necrosis factor (TNF)-alpha. This was in part due to up
      regulation of beta- and gamma-ENaC subunit expression. Endiandrin A potentiated
      GR-mediated transcription by increasing GR protein expression and
      phosphorylation. It inhibited c-Jun N-terminal kinase (JNK) activation induced by
      dexamethasone and/or TNF-alpha and increased levels of GR localized to the
      nucleus. Additionally, endiandrin A increased the serum- and glucocorticoid
      induced kinase (sgk)-1 via activation of p38. Finally, the regulation of ENaC
      function by endiandrin A was confirmed in rat native colon. In conclusion,
      endiandrin A potentiates glucocorticoid-driven activation of colonic epithelial
      sodium channels via JNK inhibition and p38 activation due to transcriptional up
      regulation of beta- and gamma-ENaC-subunits along with induction of sgk-1.

PMID- 23152906
TI  - High levels of aromatic amino acids in gastric juice during the early stages of
      gastric cancer progression.
AB  - BACKGROUND: Early-stage gastric cancer is mostly asymptomatic and can easily be
      missed easily by conventional gastroscopy. Currently, there are no useful
      biomarkers for the early detection of gastric cancer, and their identification of
      biomarkers is urgently needed. METHODS: Gastric juice was obtained from 185
      subjects that were divided into three groups: non-neoplastic gastric disease
      (NGD), advanced gastric cancer and early gastric cancer (EGC). The levels of
      aromatic amino acids in the gastric juice were quantitated using high-performance
      liquid chromatography. RESULTS: The median values (25th to 75th percentile) of
      tyrosine, phenylalanine and tryptophan in the gastric juice were 3.8 (1.7-7.5)
      ug/ml, 5.3 (2.3-9.9) ug/ml and 1.0 (0.4-2.8) ug/ml in NGD; 19.4 (5.8-72.4) ug/ml,
      24.6 (11.5-73.7) ug/ml and 8.3 (2.1-28.0) ug/ml in EGC. Higher levels of
      tyrosine, phenylalanine and tryptophan in the gastric juice were observed in
      individuals of EGC groups compared those of the NGD group (NGD vs. EGC,
      P<0.0001). For the detection of EGC, the areas under the receiver operating
      characteristic curves (AUCs) of each biomarker were as follows: tyrosine, 0.790
      [95% confidence interval (CI), 0.703-0.877]; phenylalanine, 0.831 (95% CI, 0.750
      0.911); and tryptophan, 0.819 (95% CI, 0.739-0.900). The sensitivity and
      specificity of phenylalanine were 75.5% and 81.4%, respectively, for detection of
      EGC. A multiple logistic regression analysis showed that high levels of aromatic
      amino acids in the gastric juice were associated with gastric cancer (adjusted
      beta coefficients ranged from 1.801 to 4.414, P<0.001). CONCLUSION: Increased
      levels of tyrosine, phenylalanine and tryptophan in the gastric juice samples
      were detected in the early phase of gastric carcinogenesis. Thus, tyrosine,
      phenylalanine and tryptophan in gastric juice could be used as biomarkers for the
      early detection of gastric cancer. A gastric juice analysis is an efficient,
      economical and convenient method for screening early gastric cancer development
      in the general population.

PMID- 23152907
TI  - Structure-function analysis of the glioma targeting NFL-TBS.40-63 peptide
      corresponding to the tubulin-binding site on the light neurofilament subunit.
AB  - We previously reported that a 24 amino acid peptide (NFL-TBS.40-63) corresponding
      to the tubulin-binding site located on the light neurofilament subunit,
      selectively enters in glioblastoma cells where it disrupts their microtubule
      network and inhibits their proliferation. Here, we analyzed the structure
      function relationships using an alanine-scanning strategy, in order to identify
      residues essential for these biological activities. We showed that the majority
      of modified peptides present a decreased or total loss to penetrate in these
      cells, or to alter microtubules. Correspondingly, circular dichroism measurements
      showed that this peptide forms either beta-sheet or alpha-helix structures
      according to the solvent and that alanine substitution modified or destabilized
      the structure, in relation with changes in the biological activities. Moreover,
      substitution of serine residues by phosphoserine or aspartic acid concomitantly
      decreased the cell penetrating activity and the structure stability. These
      results indicate the importance of structure for the activities, including
      selectivity to glioblastoma cells of this peptide, and its regulation by
      phosphorylation.

PMID- 23152908
TI  - Remarkable diversity in the enzymes catalyzing the last step in synthesis of the
      pimelate moiety of biotin.
AB  - Biotin synthesis in Escherichia coli requires the functions of the bioH and bioC
      genes to synthesize the precursor pimelate moiety by use of a modified fatty acid
      biosynthesis pathway. However, it was previously noted that bioH has been
      replaced with bioG or bioK within the biotin synthetic gene clusters of other
      bacteria. We report that each of four BioG proteins from diverse bacteria and two
      cyanobacterial BioK proteins functionally replace E. coli BioH in vivo. Moreover,
      purified BioG proteins have esterase activity against pimeloyl-ACP methyl ester,
      the physiological substrate of BioH. Two of the BioG proteins block biotin
      synthesis when highly expressed and these toxic proteins were shown to have more
      promiscuous substrate specificities than the non-toxic BioG proteins. A
      postulated BioG-BioC fusion protein was shown to functionally replace both the
      BioH and BioC functions of E. coli. Although the BioH, BioG and BioK esterases
      catalyze a common reaction, the proteins are evolutionarily distinct.

PMID- 23152909
TI  - Age and gender differences in the social patterning of cardiovascular risk
      factors in Switzerland: the CoLaus study.
AB  - OBJECTIVES: We examined the social distribution of a comprehensive range of
      cardiovascular risk factors (CVRF) in a Swiss population and assessed whether
      socioeconomic differences varied by age and gender. METHODS: Participants were
      2960 men and 3343 women aged 35-75 years from a population-based survey conducted
      in Lausanne, Switzerland (CoLaus study). Educational level was the indicator of
      socioeconomic status used in this study. Analyses were stratified by gender and
      age group (35-54 years; 55-75 years). RESULTS: There were large educational
      differences in the prevalence of CVRF such as current smoking (Delta = absolute
      difference in prevalence between highest and lowest educational group:15.1%/12.6%
      in men/women aged 35-54 years), physical inactivity (Delta = 25.3%/22.7% in
      men/women aged 35-54 years), overweight and obesity (Delta = 14.6%/14.8% in
      men/women aged 55-75 years for obesity), hypertension (Delta = 16.7%/11.4% in
      men/women aged 55-75 years), dyslipidemia (Delta = 2.8%/6.2% in men/women aged 35
      54 years for high LDL-cholesterol) and diabetes (Delta = 6.0%/2.6% in men/women
      aged 55-75 years). Educational inequalities in the distribution of CVRF were
      larger in women than in men for alcohol consumption, obesity, hypertension and
      dyslipidemia (p<0.05). Relative educational inequalities in CVRF tended to be
      greater among the younger (35-54 years) than among the older age group (55-75
      years), particularly for behavioral CVRF and abdominal obesity among men and for
      physiological CVRF among women (p<0.05). CONCLUSION: Large absolute differences
      in the prevalence of CVRF according to education categories were observed in this
      Swiss population. The socioeconomic gradient in CVRF tended to be larger in women
      and in younger persons.

PMID- 23152911
TI  - Development and characterization of recombinant ovine coagulation factor VIII.
AB  - Animal models of the bleeding disorder, hemophilia A, have been an integral
      component of the biopharmaceutical development process and have facilitated the
      development of recombinant coagulation factor VIII (fVIII) products capable of
      restoring median survival of persons with hemophilia A to that of the general
      population. However, there remain several limitations to recombinant fVIII as a
      biotherapeutic, including invasiveness of intravenous infusion, short half-life,
      immunogenicity, and lack of availability to the majority of the world's
      population. The recently described ovine model of hemophilia A is the largest and
      most accurate phenocopy. Affected sheep die prematurely due to bleeding-related
      pathogenesis and display robust adaptive humoral immunity to non-ovine fVIII.
      Herein, we describe the development and characterization of recombinant ovine
      fVIII (ofVIII) to support further the utility of the ovine hemophilia A model.
      Full-length and B-domain deleted (BDD) ofVIII cDNAs were generated and
      demonstrated to facilitate greater biosynthetic rates than their human fVIII
      counterparts while both BDD constructs showed greater expression rates than the
      same-species full-length versions. A top recombinant BDD ofVIII producing baby
      hamster kidney clone was identified and used to biosynthesize raw material for
      purification and biochemical characterization. Highly purified recombinant BDD
      ofVIII preparations possess a specific activity nearly 2-fold higher than
      recombinant BDD human fVIII and display a differential glycosylation pattern.
      However, binding to the carrier protein, von Willebrand factor, which is critical
      for stability of fVIII in circulation, is indistinguishable. Decay of thrombin
      activated ofVIIIa is 2-fold slower than human fVIII indicating greater intrinsic
      stability. Furthermore, intravenous administration of ofVIII effectively reverses
      the bleeding phenotype in the murine model of hemophilia A. Recombinant ofVIII
      should facilitate the maintenance of the ovine hemophilia A herd and their
      utilization as a relevant large animal model for the research and development of
      novel nucleic acid and protein-based therapies for hemophilia A.

PMID- 23152910
TI  - Functionally suppressive CD8 T regulatory cells are increased in patients with
      multiple myeloma: a cause for immune impairment.
AB  - BACKGROUND: Multiple myeloma (MM) is a plasma cell malignancy frequently
      associated with impaired immune cell numbers and functions. In MM, several
      studies have previously shown that CD4 regulatory T (Treg) cells hamper effector
      T cell functions and enhance immune dysfunction. In this study, we aimed to prove
      the presence of functionally suppressive Treg cells expressing CD8 phenotype (CD8
      Treg cells) in MM. To the best of our knowledge, this has not been reported
      previously in MM. METHODS: We analyzed CD8 Treg cells and their transcription
      factor FoxP3 from 64 newly diagnosed MM patients using flow cytometry and real
      time-polymerase chain reaction (RT-PCR). RNA profile of cytokines in CD8 Treg
      cells was also assessed using RT-PCR. CD8 Treg cells from 5 MM patients and 5
      healthy donors were functionally evaluated using proliferation assays. RESULTS:
      CD8 Treg cells (CD8+CD25hi+) were significantly elevated in MM patients
      (P<0.0001), and their transcription factor FoxP3 expression was also higher in MM
      (P<0.0001) compared to healthy donors which was evidenced by flow cytometry and
      RT-PCR analyses. CD8 Treg cells negatively correlated with total lymphocyte count
      (P = 0.016). Functional studies revealed that CD8 Treg cells isolated from MM
      patients and healthy donors inhibited proliferation of CD4 T cells in a
      concentration dependent manner. In the presence of CD8 Treg cells in
      proliferation assays, level of IFN-gamma was decreased but not IL-10. CD4 T cells
      from MM patients secreted abnormal level of IL-10 compared to healthy donors (P =
      0.01) in proliferation assays without CD8 Treg cells. RNA profile of cytokines
      from CD8 Treg cells did not differ significantly between MM patients and healthy
      donors. CONCLUSIONS: These findings show the presence of increased number of
      functionally suppressive CD8 Treg cells in MM patients. We believe that these
      suppressive CD8 Treg cells might enhance immune impairment and disease
      progression in MM.

PMID- 23152912
TI  - The effects of foreknowledge and task-set shifting as mirrored in cue- and target
      locked event-related potentials.
AB  - The present study examined the use of foreknowledge in a task-cueing protocol
      while manipulating sensory updating and executive control in both, informatively
      and non-informatively pre-cued trials. Foreknowledge, sensory updating (cue
      switch effects) and task-switching were orthogonally manipulated in order to
      address the question of whether, and to which extent, the sensory processing of
      cue changes can partly or totally explain the final task switch costs.
      Participants responded faster when they could prepare for the upcoming task and
      if no task-set updating was necessary. Sensory cue switches influenced cue-locked
      ERPs only when they contained conceptual information about the upcoming task:
      frontal P2 amplitudes were modulated by task-relevant cue changes, mid-parietal
      P3 amplitudes by the anticipatory updating of stimulus-response mappings, and P3
      peak latencies were modulated by task switching. Task preparation was
      advantageous for efficient stimulus-response re-mapping at target-onset as
      mirrored in target N2 amplitudes. However, N2 peak latencies indicate that this
      process is faster for all repeat trials. The results provide evidence to support
      a very fast detection of task-relevance in sensory (cue) changes and argue
      against the view of task repetition benefits as secondary to purely perceptual
      repetition priming. Advanced preparation may have a stronger influence on
      behavioral performance and target-locked brain activity than the local effect of
      repeating or switching the task-set in the current trial.

PMID- 23152913
TI  - 18beta-glycyrrhetinic acid delivered orally induces isolated lymphoid follicle
      maturation at the intestinal mucosa and attenuates rotavirus shedding.
AB  - Glycyrrhizin, an abundant bioactive component of the medicinal licorice root is
      rapidly metabolized by gut commensal bacteria into 18beta-glycyrrhetinic acid
      (GRA). Either or both of these compounds have been shown to have antiviral, anti
      hepatotoxic, anti-ulcerative, anti-tumor, anti-allergenic and anti-inflammatory
      activity in vitro or in vivo. In this study, the ability of GRA to modulate
      immune responses at the small intestinal mucosa when delivered orally was
      investigated. Analysis of cytokine transcription in duodenal and ileal tissue in
      response to GRA treatment revealed a pattern of chemokine and chemokine receptor
      gene expression predictive of B cell recruitment to the gut. Consistent with this
      finding, GRA induced increases in CD19(+) B cells in the lamina propria and
      B220(+) B cell aggregates framed by CD11c(+) dendritic cells in structures
      resembling isolated lymphoid follicles (ILF). Using a mouse model of rotavirus
      infection, GRA reduced the duration of viral antigen shedding, and endpoint serum
      antibody titers were higher in GRA-treated animals. Together the data suggest GRA
      delivered orally augments lymphocyte recruitment to the intestinal mucosa and
      induces maturation of B cell-rich ILF independently of ectopic antigenic
      stimulus. These results provide further support a role for dietary ligands in
      modulation of dynamic intestinal lymphoid tissue.

PMID- 23152914
TI  - 17-AAG kills intracellular Leishmania amazonensis while reducing inflammatory
      responses in infected macrophages.
AB  - BACKGROUND: Leishmaniasis is a neglected endemic disease with a broad spectrum of
      clinical manifestations. Pentavalent antimonials have been the treatment of
      choice for the past 70 years and, due to the emergence of resistant cases, the
      efficacy of these drugs has come under scrutiny. Second-line drugs are less
      efficacious, cause a range of side effects and can be costly. The formulation of
      new generations of drugs, especially in developing countries, has become
      mandatory. METHODOLOGY/PRINCIPAL FINDINGS: We investigated the anti-leishmanial
      effect of 17-(allylamino)-17-demethoxygeldanamycin (17-AAG), an HSP90 inhibitor,
      in vitro. This inhibitor is currently in clinical trials for cancer treatment;
      however, its effects against intracellular Leishmania remain untested.
      Macrophages infected with L. amazonensis were treated with 17-AAG (25-500 nM) and
      parasite load was quantified using optical microscopy. Parasite load declined in
      17-AAG-treated macrophages in a dose- and time-dependent manner. Intracellular
      parasite death became irreversible after 4 h of treatment with 17-AAG, and
      occurred independent of nitric oxide (NO) and superoxide (O(2) (-)) production.
      Additionally, intracellular parasite viability was severely reduced after 48 h of
      treatment. Interestingly, treatment with 17-AAG reduced pro-inflammatory mediator
      production, including TNF-alpha, IL-6 and MCP-1, yet IL-12 remained unaffected.
      Electron microscopy revealed morphological alterations, such as double-membrane
      vacuoles and myelin figures at 24 and 48 h after 17-AAG treatment.
      CONCLUSIONS/SIGNIFICANCE: The HSP90 inhibitor, 17-AAG, possesses high potency
      under low dosage and reduces both pro-inflammatory and oxidative molecule
      production. Therefore, further studies are warranted to investigate this
      inhibitor's potential in the development of new generations of anti-leishmanials.

PMID- 23152915
TI  - Abscisic acid refines the synthesis of chloroplast proteins in maize (Zea mays)
      in response to drought and light.
AB  - To better understand abscisic acid (ABA) regulation of the synthesis of
      chloroplast proteins in maize (Zea mays L.) in response to drought and light, we
      compared leaf proteome differences between maize ABA-deficient mutant vp5 and
      corresponding wild-type Vp5 green and etiolated seedlings exposed to drought
      stress. Proteins extracted from the leaves of Vp5 and vp5 seedlings were used for
      two-dimensional electrophoresis (2-DE) and subsequent matrix-assisted laser
      desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry (MS). After
      Coomassie brilliant blue staining, approximately 450 protein spots were
      reproducibly detected on 2-DE gels. A total of 36 differentially expressed
      protein spots in response to drought and light were identified using MALDI-TOF MS
      and their subcellular localization was determined based on the annotation of
      reviewed accession in UniProt Knowledgebase and the software prediction. As a
      result, corresponding 13 proteins of the 24 differentially expressed protein
      spots were definitely localized in chloroplasts and their expression was in an
      ABA-dependent way, including 6 up-regulated by both drought and light, 5 up
      regulated by drought but down-regulated by light, 5 up-regulated by light but
      down-regulated by drought; 5 proteins down-regulated by drought were mainly those
      involved in photosynthesis and ATP synthesis. Thus, the results in the present
      study supported the vital role of ABA in regulating the synthesis of drought-
      and/or light-induced proteins in maize chloroplasts and would facilitate the
      functional characterization of ABA-induced chloroplast proteins in C(4) plants.

PMID- 23152916
TI  - Egr2::cre mediated conditional ablation of dicer disrupts histogenesis of
      mammalian central auditory nuclei.
AB  - Histogenesis of the auditory system requires extensive molecular orchestration.
      Recently, Dicer1, an essential gene for generation of microRNAs, and miR-96 were
      shown to be important for development of the peripheral auditory system. Here, we
      investigated their role for the formation of the auditory brainstem. Egr2::Cre
      mediated early embryonic ablation of Dicer1 caused severe disruption of auditory
      brainstem structures. In adult animals, the volume of the cochlear nucleus
      complex (CNC) was reduced by 73.5%. This decrease is in part attributed to the
      lack of the microneuronal shell. In contrast, fusiform cells, which similar to
      the granular cells of the microneural shell are derived from Egr2 positive cells,
      were still present. The volume reduction of the CNC was already present at birth
      (67.2% decrease). The superior olivary complex was also drastically affected in
      these mice. Nissl staining as well as Vglut1 and Calbindin 1 immunolabeling
      revealed that principal SOC nuclei such as the medial nucleus of the trapezoid
      body and the lateral superior olive were absent. Only choline acetyltransferase
      positive neurons of the olivocochlear bundle were observed as a densely packed
      cell group in the ventrolateral area of the SOC. Mid-embryonic ablation of Dicer1
      in the ventral cochlear nucleus by Atoh7::Cre-mediated recombination resulted in
      normal formation of the cochlear nucleus complex, indicating an early embryonic
      requirement of Dicer1. Quantitative RT-PCR analysis of miR-96 demonstrated low
      expression in the embryonic brainstem and up-regulation thereafter, suggesting
      that other microRNAs are required for proper histogenesis of the auditory
      brainstem. Together our data identify a critical role of Dicer activity during
      embryonic development of the auditory brainstem.

PMID- 23152917
TI  - Compartmentalization of mammalian pantothenate kinases.
AB  - The pantothenate kinases (PanK) catalyze the first and the rate-limiting step in
      coenzyme A (CoA) biosynthesis and regulate the amount of CoA in tissues by
      differential isoform expression and allosteric interaction with metabolic
      ligands. The four human and mouse PanK proteins share a homologous carboxy
      terminal catalytic domain, but differ in their amino-termini. These unique
      termini direct the isoforms to different subcellular compartments. PanK1alpha
      isoforms were exclusively nuclear, with preferential association with the
      granular component of the nucleolus during interphase. PanK1alpha also associated
      with the perichromosomal region in condensing chromosomes during mitosis. The
      PanK1beta and PanK3 isoforms were cytosolic, with a portion of PanK1beta
      associated with clathrin-associated vesicles and recycling endosomes. Human
      PanK2, known to associate with mitochondria, was specifically localized to the
      intermembrane space. Human PanK2 was also detected in the nucleus, and functional
      nuclear localization and export signals were identified and experimentally
      confirmed. Nuclear PanK2 trafficked from the nucleus to the mitochondria, but not
      in the other direction, and was absent from the nucleus during G2 phase of the
      cell cycle. The localization of human PanK2 in these two compartments was in
      sharp contrast to mouse PanK2, which was exclusively cytosolic. These data
      demonstrate that PanK isoforms are differentially compartmentalized allowing them
      to sense CoA homeostasis in different cellular compartments and enable
      interaction with regulatory ligands produced in these same locations.

PMID- 23152918
TI  - Natural variation in the Drosophila melanogaster clock gene period modulates
      splicing of its 3'-terminal intron and mid-day siesta.
AB  - Drosophila melanogaster exhibits circadian (?24 hr) regulated morning and evening
      bouts of activity that are separated by a mid-day siesta. Increases in daily
      ambient temperature are accompanied by a progressively longer mid-day siesta and
      delayed evening activity. Presumably, this behavioral plasticity reflects an
      adaptive response that endows D. melanogaster with the ability to temporally
      optimize daily activity levels over a wide range of physiologically relevant
      temperatures. For example, the shift in activity towards the cooler nighttime
      hours on hot days might minimize the risks associated with exposure to mid-day
      heat, whereas on cold days activity is favored during the warmer daytime hours.
      These temperature-induced shifts in the distribution of daily activity are partly
      based on the thermal sensitive splicing of an intron found in the 3' untranslated
      region (UTR) of the circadian clock gene termed period (per). As temperature
      decreases, splicing of this 3'-terminal intron (termed dmpi8) is gradually
      increased, which is causally linked to a shorter mid-day siesta. Herein we
      identify several natural polymorphisms in the per 3' UTR from wild-caught
      populations of flies originating along the east coast of the United States. Two
      non-intronic closely spaced single nucleotide polymorphisms (SNPs) modulate dmpi8
      splicing efficiency, with the least efficiently spliced version associated with a
      longer mid-day siesta, especially at lower temperatures. Although these SNPs
      modulate the splicing efficiency of dmpi8 they have little to no effect on its
      thermal responsiveness, consistent with the notion that the suboptimal 5' and 3'
      splice sites of the dmpi8 intron are the primary cis-acting elements mediating
      temperature regulation. Our results demonstrate that natural variations in the
      per gene can modulate the splicing efficiency of the dmpi8 intron and the daily
      distribution of activity, providing natural examples for the involvement of dmpi8
      splicing in the thermal adaptation of behavioral programs in D. melanogaster.

PMID- 23152919
TI  - Phylogenetic patterns of geographical and ecological diversification in the
      subgenus Drosophila.
AB  - Colonisation of new geographic regions and/or of new ecological resources can
      result in rapid species diversification into the new ecological niches available.
      Members of the subgenus Drosophila are distributed across the globe and show a
      large diversity of ecological niches. Furthermore, taxonomic classification of
      Drosophila includes the rank radiation, which refers to closely related species
      groups. Nevertheless, it has never been tested if these taxonomic radiations
      correspond to evolutionary radiations. Here we present a study of the patterns of
      diversification of Drosophila to test for increased diversification rates in
      relation to the geographic and ecological diversification processes. For this, we
      have estimated and dated a phylogeny of 218 species belonging to the major
      species groups of the subgenus. The obtained phylogenies are largely consistent
      with previous studies and indicate that the major groups appeared during the
      Oligocene/Miocene transition or early Miocene, characterized by a trend of
      climate warming with brief periods of glaciation. Ancestral reconstruction of
      geographic ranges and ecological resource use suggest at least two dispersals to
      the Neotropics from the ancestral Asiatic tropical disribution, and several
      transitions to specialized ecological resource use (mycophagous and cactophilic).
      Colonisation of new geographic regions and/or of new ecological resources can
      result in rapid species diversification into the new ecological niches available.
      However, diversification analyses show no significant support for adaptive
      radiations as a result of geographic dispersal or ecological resource shift.
      Also, cactophily has not resulted in an increase in the diversification rate of
      the repleta and related groups. It is thus concluded that the taxonomic
      radiations do not correspond to adaptive radiations.

PMID- 23152920
TI  - The anti-epileptic drug valproic acid (VPA) inhibits steroidogenesis in bovine
      theca and granulosa cells in vitro.
AB  - Valproic acid (VPA) is used widely to treat epilepsy and bipolar disorder. Women
      undergoing VPA treatment reportedly have an increased incidence of polycystic
      ovarian syndrome (PCOS)-like symptoms including hyperandrogenism and oligo- or
      amenorrhoea. To investigate potential direct effects of VPA on ovarian
      steroidogenesis we used primary bovine theca (TC) and granulosa (GC) cells
      maintained under conditions that preserve their 'follicular' phenotype. Effects
      of VPA (7.8-500 ug/ml) on TC were tested with/without LH. Effects of VPA on GC
      were tested with/without FSH or IGF analogue. VPA reduced (P<0.0001) both basal
      (70% suppression; IC(50) 67+/-10 ug/ml) and LH-induced (93% suppression; IC(50)
      58+/-10 ug/ml) androstenedione secretion by TC. VPA reduced CYP17A1 mRNA
      abundance (>99% decrease; P<0.0001) with lesser effects on LHR, STAR, CYP11A1 and
      HSD3B1 mRNA (<90% decrease; P<0.05). VPA only reduced TC progesterone secretion
      induced by the highest (luteinizing) LH dose tested; TC number was unaffected by
      VPA. At higher concentrations (125-500 ug/ml) VPA inhibited basal, FSH- and IGF
      stimulated estradiol secretion (P<0.0001) by GC without affecting progesterone
      secretion or cell number. VPA reversed FSH-induced upregulation of CYP19A1 and
      HSD17B1 mRNA abundance (P<0.001). The potent histone deacetylase (HDAC)
      inhibitors trichostatin A and scriptaid also suppressed TC androstenedione
      secretion and granulosal cell oestrogen secretion suggesting that the action of
      VPA reflects its HDAC inhibitory properties. In conclusion, these findings refute
      the hypothesis that VPA has a direct stimulatory action on TC androgen output. On
      the contrary, VPA inhibits both LH-dependent androgen production and FSH/IGF
      dependent estradiol production in this in vitro bovine model, likely by
      inhibition of HDAC.

PMID- 23152921
TI  - Leaf shape responds to temperature but not CO2 in Acer rubrum.
AB  - The degree of leaf dissection and the presence of leaf teeth, along with tooth
      size and abundance, inversely correlate with mean annual temperature (MAT) across
      many plant communities. These relationships form the core of several methods for
      reconstructing MAT from fossils, yet the direct selection of temperature on tooth
      morphology has not been demonstrated experimentally. It is also not known if
      atmospheric CO(2) concentration affects leaf shape, limiting confidence in
      ancient climate reconstructions because CO(2) has varied widely on geologic
      timescales. Here I report the results of growing Acer rubrum (red maple) in
      growth cabinets at contrasting temperature and CO(2) conditions. The CO(2)
      treatment imparted no significant differences in leaf size and shape, while
      plants grown at cooler temperatures tended to have more teeth and more highly
      dissected leaves. These results provide direct evidence for the selection of
      temperature on leaf shape in one species, and support a key link in many leaf
      climate methods. More broadly, these results increase confidence for using leaf
      shape in fossils to reconstruct paleoclimate.

PMID- 23152922
TI  - Comprehensive analysis of secondary dental root canal infections: a combination
      of culture and culture-independent approaches reveals new insights.
AB  - Persistence of microorganisms or reinfections are the main reasons for failure of
      root canal therapy. Very few studies to date have included culture-independent
      methods to assess the microbiota, including non-cultivable microorganisms. The
      aim of this study was to combine culture methods with culture-independent cloning
      methods to analyze the microbial flora of root-filled teeth with periradicular
      lesions. Twenty-one samples from previously root-filled teeth were collected from
      patients with periradicular lesions. Microorganisms were cultivated, isolated and
      biochemically identified. In addition, ribosomal DNA of bacteria, fungi and
      archaea derived from the same samples was amplified and the PCR products were
      used to construct clone libraries. DNA of selected clones was sequenced and
      microbial species were identified, comparing the sequences with public databases.
      Microorganisms were found in 12 samples with culture-dependent and -independent
      methods combined. The number of bacterial species ranged from 1 to 12 in one
      sample. The majority of the 26 taxa belonged to the phylum Firmicutes (14 taxa),
      followed by Actinobacteria, Proteobacteria and Bacteroidetes. One sample was
      positive for fungi, and archaea could not be detected. The results obtained with
      both methods differed. The cloning technique detected several as-yet-uncultivated
      taxa. Using a combination of both methods 13 taxa were detected that had not been
      found in root-filled teeth so far. Enterococcus faecalis was only detected in two
      samples using culture methods. Combining the culture-dependent and -independent
      approaches revealed new candidate endodontic pathogens and a high diversity of
      the microbial flora in root-filled teeth with periradicular lesions. Both methods
      yielded differing results, emphasizing the benefit of combined methods for the
      detection of the actual microbial diversity in apical periodontitis.

PMID- 23152923
TI  - The ability of virulence factor expression by Pseudomonas aeruginosa to predict
      clinical disease in hospitalized patients.
AB  - BACKGROUND: Pseudomonas aeruginosa is an opportunistic pathogen that frequently
      causes hospital acquired colonization and infection. Accurate identification of
      host and bacterial factors associated with infection could aid treatment
      decisions for patients with P. aeruginosa cultured from clinical sites. METHODS:
      We identified a prospective cohort of 248 hospitalized patients with positive P.
      aeruginosa cultures. Clinical data were analyzed to determine whether an
      individual met predefined criteria for infection versus colonization. P.
      aeruginosa isolates were tested for the expression of multiple phenotypes
      previously associated with virulence in animal models and humans. Logistic
      regression models were constructed to determine the degree of association between
      host and bacterial factors with P. aeruginosa infection of the bloodstream, lung,
      soft tissue and urinary tract. RESULTS: One host factor (i.e. diabetes mellitus),
      and one bacterial factor, a Type 3 secretion system positive phenotype, were
      significantly associated with P. aeruginosa infection in our cohort. Subgroup
      analysis of patients with P. aeruginosa isolated from the urinary tract revealed
      that the presence of a urinary tract catheter or stent was an additional factor
      for P. aeruginosa infection. CONCLUSIONS: Among hospitalized patients with
      culture-documented P. aeruginosa, infection is more likely to be present in those
      with diabetes mellitus and those harboring a Type 3 secretion positive bacterial
      strain.

PMID- 23152924
TI  - Coordination of the arc regulatory system and pheromone-mediated positive
      feedback in controlling the Vibrio fischeri lux operon.
AB  - Bacterial pheromone signaling is often governed both by environmentally
      responsive regulators and by positive feedback. This regulatory combination has
      the potential to coordinate a group response among distinct subpopulations that
      perceive key environmental stimuli differently. We have explored the interplay
      between an environmentally responsive regulator and pheromone-mediated positive
      feedback in intercellular signaling by Vibrio fischeri ES114, a bioluminescent
      bacterium that colonizes the squid Euprymna scolopes. Bioluminescence in ES114 is
      controlled in part by N-(3-oxohexanoyl)-L-homoserine lactone (3OC6), a pheromone
      produced by LuxI that together with LuxR activates transcription of the
      luxICDABEG operon, initiating a positive feedback loop and inducing luminescence.
      The lux operon is also regulated by environmentally responsive regulators,
      including the redox-responsive ArcA/ArcB system, which directly represses lux in
      culture. Here we show that inactivating arcA leads to increased 3OC6 accumulation
      to initiate positive feedback. In the absence of positive feedback, arcA-mediated
      control of luminescence was only ~2-fold, but luxI-dependent positive feedback
      contributed more than 100 fold to the net induction of luminescence in the arcA
      mutant. Consistent with this overriding importance of positive feedback, 3OC6
      produced by the arcA mutant induced luminescence in nearby wild-type cells,
      overcoming their ArcA repression of lux. Similarly, we found that artificially
      inducing ArcA could effectively repress luminescence before, but not after,
      positive feedback was initiated. Finally, we show that 3OC6 produced by a
      subpopulation of symbiotic cells can induce luminescence in other cells co
      colonizing the host. Our results suggest that even transient loss of ArcA
      mediated regulation in a sub-population of cells can induce luminescence in a
      wider community. Moreover, they indicate that 3OC6 can communicate information
      about both cell density and the state of ArcA/ArcB.

PMID- 23152925
TI  - The impact of heterogeneity and dark acceptor states on FRET: implications for
      using fluorescent protein donors and acceptors.
AB  - Forster resonance energy transfer (FRET) microscopy is widely used to study
      protein interactions in living cells. Typically, spectral variants of the Green
      Fluorescent Protein (FPs) are incorporated into proteins expressed in cells, and
      FRET between donor and acceptor FPs is assayed. As appreciable FRET occurs only
      when donors and acceptors are within 10 nm of each other, the presence of FRET
      can be indicative of aggregation that may denote association of interacting
      species. By monitoring the excited-state (fluorescence) decay of the donor in the
      presence and absence of acceptors, dual-component decay analysis has been used to
      reveal the fraction of donors that are FRET positive (i.e., in
      aggregates)._However, control experiments using constructs containing both a
      donor and an acceptor FP on the same protein repeatedly indicate that a large
      fraction of these donors are FRET negative, thus rendering the interpretation of
      dual-component analysis for aggregates between separately donor-containing and
      acceptor-containing proteins problematic. Using Monte-Carlo simulations and
      analytical expressions, two possible sources for such anomalous behavior are
      explored: 1) conformational heterogeneity of the proteins, such that variations
      in the distance separating donor and acceptor FPs and/or their relative
      orientations persist on time-scales long in comparison with the excited-state
      lifetime, and 2) FP dark states.

PMID- 23152927
TI  - Substrate mediated enzyme prodrug therapy.
AB  - In this report, we detail Substrate Mediated Enzyme Prodrug Therapy (SMEPT) as a
      novel approach in drug delivery which relies on enzyme-functionalized cell
      culture substrates to achieve a localized conversion of benign prodrug(s) into
      active therapeutics with subsequent delivery to adhering cells or adjacent
      tissues. For proof-of-concept SMEPT, we use surface adhered micro-structured
      physical hydrogels based on poly(vinyl alcohol), beta-glucuronidase enzyme and
      glucuronide prodrugs. We demonstrate enzymatic activity mediated by the assembled
      hydrogel samples and illustrate arms of control over rate of release of model
      fluorescent cargo. SMEPT was not impaired by adhering cells and afforded facile
      time - and dose - dependent uptake of the in situ generated fluorescent cargo by
      hepatic cells, HepG2. With the use of a glucuronide derivative of an anticancer
      drug, SN-38, SMEPT afforded a decrease in cell viability to a level similar to
      that achieved using parent drug. Finally, dose response was achieved using SMEPT
      and administration of judiciously chosen concentration of SN-38 glucuronide
      prodrug thus revealing external control over drug delivery using drug eluting
      surface. We believe that this highly adaptable concept will find use in diverse
      biomedical applications, specifically surface mediated drug delivery and tissue
      engineering.

PMID- 23152926
TI  - Evolution of cross-neutralizing antibody specificities to the CD4-BS and the
      carbohydrate cloak of the HIV Env in an HIV-1-infected subject.
AB  - Broadly neutralizing antibodies are considered an important part of a successful
      HIV vaccine. A better understanding of the factors underlying their development
      during infection and of the epitopes they target is needed to elicit similar
      antibody responses by vaccination. We and others reported that, on average, it
      takes 2 to 3 years for cross-reactive neutralizing antibodies to become
      detectable in the sera of HIV-1-infected subjects and that they target a limited
      number of epitopes on the HIV Envelope. Here we investigated the emergence and
      evolution of the earliest cross-reactive neutralizing antibody specificities in
      one HIV-1-infected individual, AC053. We defined two distinct epitopes on Env
      that are targeted by the broadly neutralizing antibody responses developed by
      AC053. The first specificity became evident at 3 years post infection and
      targeted the CD4-binding site of Env. Antibodies responsible for that specificity
      neutralized most, but not all, viruses susceptible to neutralization by the
      plasma antibodies of AC053. The second specificity became apparent approximately
      a year later. It was due to PG9-like antibodies, which were able to neutralize
      those viruses not susceptible to the anti-CD4-BS antibodies in AC053. These
      findings improve our understanding of the co-development of broadly neutralizing
      antibodies that target more than one epitope during natural HIV-1-infection in
      selected HIV+ subjects. They support the hypothesis that developing broadly
      neutralizing antibody responses targeting distinct epitopes by immunization could
      be feasible.

PMID- 23152928
TI  - Frequent epigenetic silencing of the folate-metabolising gene cystathionine-beta
      synthase in gastrointestinal cancer.
AB  - BACKGROUND: Both gastric and colorectal cancers (CRC) are the most frequently
      occurring malignancies worldwide with the overall survival of these patients
      remains unsatisfied. Identification of tumor suppressor genes (TSG) silenced by
      promoter CpG methylation uncovers mechanisms of tumorigenesis and identifies new
      epigenetic biomarkers for early cancer detection and prognosis assessment.
      Cystathionine-beta-synthase (CBS) functions in the folate metabolism pathway,
      which is intricately linked to methylation of genomic DNA. Dysregulation of DNA
      methylation contributes substantially to cancer development.
      METHODOLOGY/PRINCIPAL FINDINGS: To identify potential TSGs silenced by aberrant
      promoter methylation in CRC, we analyzed tumor and adjacent tissues from CRC
      cases using the Illumina Human Methylation45 BeadChip. We identified
      hypermethylation of the CBS gene in CRC samples, compared to adjacent tissues.
      Methylation and decreased mRNA expression of CBS were detected in most CRC cell
      lines by methylation-specific PCR and semiquantitative RT-PCR, as well as in
      gastric cancer. Treatment with 5-aza-2'-deoxycytidine and/or trichostatin A
      reversed methylation and restored CBS mRNA expression indicating a direct effect.
      Aberrant methylation was further detected in 31% of primary CRCs (29 of 96) and
      55% of gastric tumors (11 of 20). In contrast, methylation was seldom found in
      normal tissues adjacent to the tumor. CBS methylation was associated with KRAS
      mutations in primary CRCs (P = 0.04, by chi(2)-test). However, no association was
      found between CBS methylation or KRAS mutations with cancer relapse/metastasis in
      Stage II CRC patients. CONCLUSION: A novel finding from this study is that the
      folate metabolism enzyme CBS mRNA levels are frequently downregulated through CpG
      methylation of the CBS gene in gastric cancer and CRC, suggesting that CBS
      functions as a tumor suppressor gene. These findings warrant further study of CBS
      as an epigenetic biomarker for molecular diagnosis of gastrointestinal cancers.

PMID- 23152930
TI  - Anthrax lethal factor cleaves mouse nlrp1b in both toxin-sensitive and toxin
      resistant macrophages.
AB  - Anthrax lethal factor (LF) is the protease component of anthrax lethal toxin
      (LT). LT induces pyroptosis in macrophages of certain inbred mouse and rat
      strains, while macrophages from other inbred strains are resistant to the toxin.
      In rats, the sensitivity of macrophages to toxin-induced cell death is determined
      by the presence of an LF cleavage sequence in the inflammasome sensor Nlrp1. LF
      cleaves rat Nlrp1 of toxin-sensitive macrophages, activating caspase-1 and
      inducing cell death. Toxin-resistant macrophages, however, express Nlrp1 proteins
      which do not harbor the LF cleavage site. We report here that mouse Nlrp1b
      proteins are also cleaved by LF. In contrast to the situation in rats,
      sensitivity and resistance of Balb/cJ and NOD/LtJ macrophages does not correlate
      to the susceptibility of their Nlrp1b proteins to cleavage by LF, as both
      proteins are cleaved. Two LF cleavage sites, at residues 38 and 44, were
      identified in mouse Nlrp1b. Our results suggest that the resistance of NOD/LtJ
      macrophages to LT, and the inability of the Nlrp1b protein expressed in these
      cells to be activated by the toxin are likely due to polymorphisms other than
      those at the LF cleavage sites.

PMID- 23152929
TI  - The light chains of microtubule-associated proteins MAP1A and MAP1B interact with
      alpha1-syntrophin in the central and peripheral nervous system.
AB  - Microtubule-associated proteins of the MAP1 family (MAP1A, MAP1B, and MAP1S)
      share, among other features, a highly conserved COOH-terminal domain
      approximately 125 amino acids in length. We conducted a yeast 2-hybrid screen to
      search for proteins interacting with this domain and identified alpha1
      syntrophin, a member of a multigene family of adapter proteins involved in signal
      transduction. We further demonstrate that the interaction between the conserved
      COOH-terminal 125-amino acid domain (which is located in the light chains of
      MAP1A, MAP1B, and MAP1S) and alpha1-syntrophin is direct and occurs through the
      pleckstrin homology domain 2 (PH2) and the postsynaptic density protein 95/disk
      large/zonula occludens-1 protein homology domain (PDZ) of alpha1-syntrophin. We
      confirmed the interaction of MAP1B and alpha1-syntrophin by co-localization of
      the two proteins in transfected cells and by co-immunoprecipitation experiments
      from mouse brain. In addition, we show that MAP1B and alpha1-syntrophin partially
      co-localize in Schwann cells of the murine sciatic nerve during postnatal
      development and in the adult. However, intracellular localization of alpha1
      syntrophin and other Schwann cell proteins such as ezrin and dystrophin-related
      protein 2 (DRP2) and the localization of the axonal node of Ranvier-associated
      protein Caspr1/paranodin were not affected in MAP1B null mice. Our findings add
      to a growing body of evidence that classical MAPs are likely to be involved in
      signal transduction not only by directly modulating microtubule function, but
      also through their interaction with signal transduction proteins.

PMID- 23152931
TI  - Sphere culture of murine lung cancer cell lines are enriched with cancer
      initiating cells.
AB  - Cancer initiating cells (CICs) represent a unique cell population essential for
      the maintenance and growth of tumors. Most in vivo studies of CICs utilize human
      tumor xenografts in immunodeficient mice. These models provide limited
      information on the interaction of CICs with the host immune system and are of
      limited value in assessing therapies targeting CICs, especially immune-based
      therapies. To assess this, a syngeneic cancer model is needed. We examined the
      sphere-forming capacity of thirteen murine lung cancer cell lines and identified
      TC-1 and a metastatic subclone of Lewis lung carcinoma (HM-LLC) as cell lines
      that readily formed and maintained spheres over multiple passages. TC-1
      tumorspheres were not enriched for expression of CD133 or CD44, putative CIC
      markers, nor did they demonstrate Hoechst 33342 side population staining or
      Aldefluor activity compared to adherent TC-1 cells. However, in tumorsphere
      culture, these cells exhibited self-renewal and long-term symmetric division
      capacity and expressed more Oct-4 compared to adherent cells. HM-LLC sphere
      derived cells exhibited increased Oct-4, CD133, and CD44 expression, demonstrated
      a Hoechst 33342 side population and Aldefluor activity compared to adherent cells
      or a low metastatic subclone of LLC (LM-LLC). In syngeneic mice, HM-LLC sphere
      derived cells required fewer cells to initiate tumorigenesis compared to adherent
      or LM-LLC cells. Similarly TC-1 sphere-derived cells were more tumorigenic than
      adherent cells in syngeneic mice. In contrast, in immunocompromised mice, less
      than 500 sphere or adherent TC-1 cells and less than 1,000 sphere or adherent LLC
      cells were required to initiate a tumor. We suggest that no single phenotypic
      marker can identify CICs in murine lung cancer cell lines. Tumorsphere culture
      may provide an alternative approach to identify and enrich for murine lung CICs.
      Furthermore, we propose that assessing tumorigenicity of murine lung CICs in
      syngeneic mice better models the interaction of CICs with the host immune system.

PMID- 23152932
TI  - Lack of bcr and abr promotes hypoxia-induced pulmonary hypertension in mice.
AB  - BACKGROUND: Bcr and Abr are GTPase activating proteins that specifically
      downregulate activity of the small GTPase Rac in restricted cell types in vivo.
      Rac1 is expressed in smooth muscle cells, a critical cell type involved in the
      pathogenesis of pulmonary hypertension. The molecular mechanisms that underlie
      hypoxia-associated pulmonary hypertension are not well-defined.
      METHODOLOGY/PRINCIPAL FINDINGS: Bcr and abr null mutant mice were compared to
      wild type controls for the development of pulmonary hypertension after exposure
      to hypoxia. Also, pulmonary arterial smooth muscle cells from those mice were
      cultured in hypoxia and examined for proliferation, p38 activation and IL-6
      production. Mice lacking Bcr or Abr exposed to hypoxia developed increased right
      ventricular pressure, hypertrophy and pulmonary vascular remodeling. Perivascular
      leukocyte infiltration in the lungs was increased, and under hypoxia bcr-/- and
      abr-/- macrophages generated more reactive oxygen species. Consistent with a
      contribution of inflammation and oxidative stress in pulmonary hypertension
      associated vascular damage, Bcr and Abr-deficient animals showed elevated
      endothelial leakage after hypoxia exposure. Hypoxia-treated pulmonary arterial
      smooth muscle cells from Bcr- or Abr-deficient mice also proliferated faster than
      those of wild type mice. Moreover, activated Rac1, phosphorylated p38 and
      interleukin 6 were increased in these cells in the absence of Bcr or Abr.
      Inhibition of Rac1 activation with Z62954982, a novel Rac inhibitor, decreased
      proliferation, p38 phosphorylation and IL-6 levels in pulmonary arterial smooth
      muscle cells exposed to hypoxia. CONCLUSIONS: Bcr and Abr play a critical role in
      down-regulating hypoxia-induced pulmonary hypertension by deactivating Rac1 and,
      through this, reducing both oxidative stress generated by leukocytes as well as
      p38 phosphorylation, IL-6 production and proliferation of pulmonary arterial
      smooth muscle cells.

PMID- 23152933
TI  - Allele-specific gene silencing in two mouse models of autosomal dominant skeletal
      myopathy.
AB  - We explored the potential of mutant allele-specific gene silencing (ASGS) in
      providing therapeutic benefit in two established mouse models of the autosomal
      dominantly-inherited muscle disorders, Malignant Hyperthermia (MH) and Central
      Core Disease (CCD). Candidate ASGS siRNAs were designed and validated for
      efficacy and specificity on ryanodine receptor (RyR1) cDNA mini-constructs
      expressed in HEK293 cells using RT-PCR- and confocal microscopy-based assays. In
      vivo delivery of the most efficacious identified siRNAs into flexor digitorum
      brevis (FDB) muscles was achieved by injection/electroporation of footpads of 4-6
      month old heterozygous Ryr1(Y524S/+) (YS/+) and Ryr1(I4895T/+) (IT/+) knock-in
      mice, established mouse models of MH with cores and CCD, respectively. Treatment
      of IT/+ mice resulted in a modest rescue of deficits in the maximum rate (~38%
      rescue) and magnitude (~78%) of ligand-induced Ca(2+) release that occurred in
      the absence of a change in the magnitude of electrically-evoked Ca(2+) release.
      Compared to the difference between the caffeine sensitivity of Ca(2+) release in
      FDB fibers from YS/+ and WT mice treated with SCR siRNA (EC(50): 1.1 mM versus
      4.4 mM, respectively), caffeine sensitivity was normalized in FDB fibers from
      YS/+ mice following 2 (EC(50): 2.8 mM) and 4 week (EC(50): 6.6 mM) treatment with
      YS allele-specific siRNA. Moreover, the temperature-dependent increase in resting
      Ca(2+) observed in FDB fibers from YS/+ mice was normalized to WT levels after 2
      weeks of treatment with YS allele-specific siRNA. As determined by quantitative
      real time PCR, the degree of functional rescue in YS/+ and IT/+ mice correlated
      well with the relative increase in fractional WT allele expression.

PMID- 23152934
TI  - Environmental contamination as a risk factor for intra-household Staphylococcus
      aureus transmission.
AB  - BACKGROUND: The household is a recognized community reservoir for Staphylococcus
      aureus. This study investigated potential risk factors for intra-household S.
      aureus transmission, including the contribution of environmental contamination.
      METHODS: We investigated intra-household S. aureus transmission using a sample of
      multiple member households from a community-based case-control study examining
      risk factors for CA-MRSA infection conducted in Northern Manhattan. During a home
      visit, index subjects completed a questionnaire. All consenting household members
      were swabbed, as were standardized environmental household items. Swabs were
      cultured for S. aureus. Positive isolates underwent further molecular
      characterization. Intra-household transmission was defined as having identical
      strains among two or more household members. Multiple logistic regression was
      used to identify independent risk factors for transmission. RESULTS: We enrolled
      291 households: 146 index cases, 145 index controls and 687 of their household
      contacts. The majority of indexes were Hispanic (85%), low income (74%), and
      female (67%), with a mean age of 31 (range 1-79). The average size of case and
      control households was 4 people. S. aureus colonized individuals in 62% of
      households and contaminated the environment in 54% of households. USA300 was the
      predominant clinical infection, colonizing and environmental strain. Eighty-one
      households had evidence of intra-household transmission: 55 (38%) case and 26
      (18%) control households (P<.01). Environmental contamination with a colonizing
      or clinical infection strain (aOR: 5.4 [2.9-10.3] P<.01) and the presence of a
      child under 5 (aOR: 2.3 [1.2-4.5] P = .02) were independently associated with
      transmission. In separate multivariable models, environmental contamination was
      associated with transmission among case (aOR 3.3, p<.01) and control households
      (aOR 27.2, p<.01). CONCLUSIONS: Environmental contamination with a colonizing or
      clinical infection strain was significantly and independently associated with
      transmission in a large community-based sample. Environmental contamination
      should be considered when treating S. aureus infections, particularly among
      households with multiple infected members.

PMID- 23152935
TI  - Quantitative, spectrally-resolved intraoperative fluorescence imaging.
AB  - Intraoperative visual fluorescence imaging (vFI) has emerged as a promising aid
      to surgical guidance, but does not fully exploit the potential of the fluorescent
      agents that are currently available. Here, we introduce a quantitative
      fluorescence imaging (qFI) approach that converts spectrally-resolved data into
      images of absolute fluorophore concentration pixel-by-pixel across the surgical
      field of view (FOV). The resulting estimates are linear, accurate, and precise
      relative to true values, and spectral decomposition of multiple fluorophores is
      also achieved. Experiments with protoporphyrin IX in a glioma rodent model
      demonstrate in vivo quantitative and spectrally-resolved fluorescence imaging of
      infiltrating tumor margins for the first time. Moreover, we present images from
      human surgery which detect residual tumor not evident with state-of-the-art vFI.
      The wide-field qFI technique has broad implications for intraoperative surgical
      guidance because it provides near real-time quantitative assessment of multiple
      fluorescent biomarkers across the operative field.

PMID- 23152937
TI  - X-ray absorption near edge spectroscopy with a superconducting detector for
      nitrogen dopants in SiC.
AB  - Fluorescence-yield X-ray absorption fine structure (FY-XAFS) is extensively used
      for investigating atomic-scale local structures around specific elements in
      functional materials. However, conventional FY-XAFS instruments frequently cannot
      cover trace light elements, for example dopants in wide gap semiconductors,
      because of insufficient energy resolution of semiconductor X-ray detectors. Here
      we introduce a superconducting XAFS (SC-XAFS) apparatus to measure X-ray
      absorption near-edge structure (XANES) of n-type dopant N atoms (4 *10(19) cm(
      3)) implanted at 500 degrees C into 4H-SiC substrates annealed subsequently. The
      XANES spectra and ab initio multiple scattering calculations indicate that the N
      atoms almost completely substitute for the C sites, associated with a possible
      existence of local CN regions, in the as-implanted state. This is a reason why
      hot implantation is necessary for dopant activation in ion implantation. The SC
      XAFS apparatus may play an important role in improving doping processes for
      energy-saving wide-gap semiconductors and other functional materials.

PMID- 23152936
TI  - Hkat, a novel nutritionally regulated transmembrane protein in adipose tissues.
AB  - White adipose tissue is an active endocrine organ regulating many aspects of
      whole body physiology and pathology. Adipogenesis, a process in which premature
      cells differentiate into adipocytes, is a complex process that includes
      orchestrated changes in gene expression and cell morphology in response to
      various nutritional and hormonal stimuli. To profile transcriptome changes in
      response to nutritional stimulation, we performed RNA-seq on fat in mice treated
      with either a high-fat diet or fasting. We identified a novel nutritionally
      regulated gene, Gm12824, named Hkat (heart, kidney, adipose-enriched
      transmembrane protein). We show that both fasting and obesity dramatically reduce
      Hkat in white adipose tissue, and that fasting reduces while obesity increases
      its expression in brown fat. Hkat is localized to the plasma membrane and induced
      during adipogenesis. Therefore, Hkat is a novel nutritionally regulated gene that
      is potentially involved in metabolism.

PMID- 23152938
TI  - Spatial organization of foreshocks as a tool to forecast large earthquakes.
AB  - An increase in the number of smaller magnitude events, retrospectively named
      foreshocks, is often observed before large earthquakes. We show that the linear
      density probability of earthquakes occurring before and after small or
      intermediate mainshocks displays a symmetrical behavior, indicating that the size
      of the area fractured during the mainshock is encoded in the foreshock spatial
      organization. This observation can be used to discriminate spatial clustering due
      to foreshocks from the one induced by aftershocks and is implemented in an alarm
      based model to forecast m > 6 earthquakes. A retrospective study of the last 19
      years Southern California catalog shows that the daily occurrence probability
      presents isolated peaks closely located in time and space to the epicenters of
      five of the six m > 6 earthquakes. We find daily probabilities as high as 25% (in
      cells of size 0.04 * 0.04deg(2)), with significant probability gains with respect
      to standard models.

PMID- 23152939
TI  - Lipid-coated hydrogel shapes as components of electrical circuits and mechanical
      devices.
AB  - Recently, two-dimensional networks of aqueous droplets separated by lipid
      bilayers, with engineered protein pores as functional elements, were used to
      construct millimeter-sized devices such as a light sensor, a battery, and half-
      and full-wave rectifiers. Here, for the first time, we show that hydrogel shapes,
      coated with lipid monolayers, can be used as building blocks for such networks,
      yielding scalable electrical circuits and mechanical devices. Examples include a
      mechanical switch, a rotor driven by a magnetic field and painted circuits,
      analogous to printed circuit boards, made with centimeter-length agarose wires.
      Bottom-up fabrication with lipid-coated hydrogel shapes is therefore a useful
      step towards the synthetic biology of functional devices including minimal
      tissues.

PMID- 23152940
TI  - A facile route for 3D aerogels from nanostructured 1D and 2D materials.
AB  - Aerogels have numerous applications due to their high surface area and low
      densities. However, creating aerogels from a large variety of materials has
      remained an outstanding challenge. Here, we report a new methodology to enable
      aerogel production with a wide range of materials. The method is based on the
      assembly of anisotropic nano-objects (one-dimensional (1D) nanotubes, nanowires,
      or two-dimensional (2D) nanosheets) into a cross-linking network from their
      colloidal suspensions at the transition from the semi-dilute to the isotropic
      concentrated regime. The resultant aerogels have highly porous and ultrafine
      three-dimensional (3D) networks consisting of 1D (Ag, Si, MnO(2), single-walled
      carbon nanotubes (SWNTs)) and 2D materials (MoS(2), graphene, h-BN) with high
      surface areas, low densities, and high electrical conductivities. This method
      opens up a facile route for aerogel production with a wide variety of materials
      and tremendous opportunities for bio-scaffold, energy storage, thermoelectric,
      catalysis, and hydrogen storage applications.

PMID- 23152941
TI  - Rogue events in the group velocity horizon.
AB  - The concept of rogue waves arises from a mysterious and potentially calamitous
      phenomenon of oceanic surfaces. There is mounting evidence that they are actually
      commonplace in a variety of different physical settings. A set of defining
      criteria has been advanced; this set is of great generality and therefore
      applicable to a wide class of systems. The question arises naturally whether
      there are generic mechanisms responsible for extreme events in different systems.
      Here we argue that under suitable circumstances nonlinear interaction between
      weak and strong waves results in intermittent giant waves with all the signatures
      of rogue waves. To obtain these circumstances only a few basic conditions must be
      met. Then reflection of waves at the so-called group-velocity horizon occurs. The
      connection between rogue waves and event horizons, seemingly unrelated physical
      phenomena, is identified as a feature common in many different physical systems.

PMID- 23152943
TI  - Super elastic strain limit in metallic glass films.
AB  - On monolithic Ni-Nb metallic glass films, we experimentally revealed 6.6% elastic
      strain limit by in-situ transmission electron microscopy observations. The origin
      of high elastic strain limit may link with high free volume in the film, causing
      the rearrangement of loosely bonded atomic clusters (or atoms) upon elastic
      deformation. This high elastic limit of metallic glass films will shed light on
      new application fields for metallic glasses, and also trigger more studies for
      deformation mechanism of amorphous materials in general.

PMID- 23152942
TI  - Highly enantioselective cascade transformations by merging heterogeneous
      transition metal catalysis with asymmetric aminocatalysis.
AB  - The concept of combining heterogeneous transition metal and amine catalysis for
      enantioselective cascade reactions has not yet been realized. This is of great
      advantage since it would allow for the recycling of expensive and non
      environmentally friendly transition metals. We disclose that the use of a
      heterogeneous Pd-catalyst in combination with a simple chiral amine co-catalyst
      allows for highly enantioselective cascade transformations. The preparative power
      of this process has been demonstrated in the context of asymmetric cascade
      Michael/carbocyclization transformations that delivers cyclopentenes bearing an
      all carbon quaternary stereocenters in high yields with up to 30:1 dr and 99% ee.
      Moreover, a variety of highly enantioselective cascade hetero
      Michael/carbocyclizations were developed for the one-pot synthesis of valuable
      dihydrofurans and pyrrolidines (up to 98% ee) by using bench-stable heterogeneous
      Pd and chiral amines as co-catalysts.

PMID- 23152944
TI  - Tunable and sizable band gap in silicene by surface adsorption.
AB  - Opening a sizable band gap without degrading its high carrier mobility is as
      vital for silicene as for graphene to its application as a high-performance field
      effect transistor (FET). Our density functional theory calculations predict that
      a band gap is opened in silicene by single-side adsorption of alkali atom as a
      result of sublattice or bond symmetry breaking. The band gap size is controllable
      by changing the adsorption coverage, with an impressive maximum band gap up to
      0.50 eV. The ab initio quantum transport simulation of a bottom-gated FET based
      on a sodium-covered silicene reveals a transport gap, which is consistent with
      the band gap, and the resulting on/off current ratio is up to 10(8). Therefore, a
      way is paved for silicene as the channel of a high-performance FET.

PMID- 23152945
TI  - Consequences of replacing EGFR juxtamembrane domain with an unstructured
      sequence.
AB  - EGFR is the best studied receptor tyrosine kinase. Yet, a comprehensive
      mechanistic understanding of EGFR signaling is lacking, despite very active
      research in the field. In this paper, we investigate the role of the
      juxtamembrane (JM) domain in EGFR signaling by replacing it with a (GGS)(10)
      unstructured sequence. We probe the effect of this replacement on (i) EGFR
      phosphorylation, (ii) EGFR dimerization and (iii) ligand (EGF) binding. We show
      that the replacement of EGFR JM domain with a (GGS)(10) unstructured linker
      completely abolishes the phosphorylation of all tyrosine residues, without
      measurable effects on receptor dimerization or ligand binding. Our results
      suggest that the JM domain does not stabilize the inactive EGFR dimer in the
      absence of ligand, and is likely critical only for the last step of EGFR
      activation, the ligand-induced transition from the inactive to active dimer.

PMID- 23152946
TI  - Active dielectric antenna on chip for spatial light modulation.
AB  - Integrated photonic resonators are widely used to manipulate light propagation in
      an evanescently-coupled waveguide. While the evanescent coupling scheme works
      well for planar optical systems that are naturally waveguide based, many optical
      applications are free-space based, such as imaging, display, holographics,
      metrology and remote sensing. Here we demonstrate an active dielectric antenna as
      the interface device that allows the large-scale integration capability of
      silicon photonics to serve the free-space applications. We show a novel
      perturbation-base diffractive coupling scheme that allows a high-Q planer
      resonator to directly interact with and manipulate free-space waves. Using a
      silicon-based photonic crystal cavity whose resonance can be rapidly tuned with a
      p-i-n junction, a compact spatial light modulator with an extinction ratio of 9.5
      dB and a modulation speed of 150 MHz is demonstrated. Method to improve the
      modulation speed is discussed.

PMID- 23152947
TI  - Exploring the ultrashort pulse laser parameter space for membrane
      permeabilisation in mammalian cells.
AB  - The use of ultrashort femtosecond pulsed lasers to effect membrane
      permeabilisation and initiate both optoinjection and transfection of cells has
      recently seen immense interest. We investigate femtosecond laser-induced membrane
      permeabilisation in mammalian cells as a function of pulse duration, pulse energy
      and number of pulses, by quantifying the efficiency of optoinjection for these
      parameters. Depending on pulse duration and pulse energy we identify two distinct
      membrane permeabilisation regimes. In the first regime a nonlinear dependence of
      order 3.4-9.6 is exhibited below a threshold peak power of at least 6 kW. Above
      this threshold peak power, the nonlinear dependence is saturated resulting in
      linear behaviour. This indicates that the membrane permeabilisation mechanism
      requires efficient multiphoton absorption to produce free electrons but once this
      process saturates, linear absorption dominates. Our experimental findings support
      a previously proposed theoretical model and provide a step towards the
      optimisation of laser-mediated gene delivery into mammalian cells.

PMID- 23152948
TI  - Tunable acoustic double negativity metamaterial.
AB  - Man-made composite materials called "metamaterials" allow for the creation of
      unusual wave propagation behavior. Acoustic and elastic metamaterials in
      particular, can pave the way for the full control of sound in realizing cloaks of
      invisibility, perfect lenses and much more. In this work we design acousto
      elastic surface modes that are similar to surface plasmons in metals and on
      highly conducting surfaces perforated by holes. We combine a structure hosting
      these modes together with a gap material supporting negative modulus and
      collectively producing negative dispersion. By analytical techniques and full
      wave simulations we attribute the observed behavior to the mass density and bulk
      modulus being simultaneously negative.

PMID- 23152949
TI  - Using Multiple Phenotype Assays and Epistasis Testing to Enhance the Reliability
      of RNAi Screening and Identify Regulators of Muscle Protein Degradation.
AB  - RNAi is a convenient, widely used tool for screening for genes of interest. We
      have recently used this technology to screen roughly 750 candidate genes, in C.
      elegans, for potential roles in regulating muscle protein degradation in vivo. To
      maximize confidence and assess reproducibility, we have only used previously
      validated RNAi constructs and have included time courses and replicates. To
      maximize mechanistic understanding, we have examined multiple sub-cellular
      phenotypes in multiple compartments in muscle. We have also tested knockdowns of
      putative regulators of degradation in the context of mutations or drugs that were
      previously shown to inhibit protein degradation by diverse mechanisms. Here we
      discuss how assaying multiple phenotypes, multiplexing RNAi screens with use of
      mutations and drugs, and use of bioinformatics can provide more data on rates of
      potential false positives and negatives as well as more mechanistic insight than
      simple RNAi screening. 

PMID- 23152951
TI  - Absorption spectroscopy in microfluidic flow cells using a metal clad leaky
      waveguide device with a porous gel waveguide layer.
AB  - Broadband absorption spectroscopy is advantageous because the full spectral
      profile of an analyte can permit identification of species. This work for the
      first time investigates the feasibility of a metal clad leaky waveguide (MCLW)
      device to obtain an absorption spectrum of an analyte of interest, methylene
      blue, using a white light source in a microfluidic flow cell. The MCLW device
      comprises a porous low refractive index gel, agarose, deposited on a titanium
      coated glass slide. The device was capable of detecting 2.3 MUM of methylene blue
      at a wavelength of 650 nm. The corresponding minimum detectable absorbance is 1.6
      * 10(-1) cm(-1). In comparison to commonly used detection devices the MCLW is
      simpler, robust, easier to fabricate and can be easily interfaced to microfluidic
      devices. It was also possible to store the MCLW devices dry for up to a year and
      rehydrate them in 30 s to a working condition.

PMID- 23152950
TI  - Comparative Analysis of the Immunomodulatory Properties of Equine Adult-Derived
      Mesenchymal Stem Cells().
AB  - Mesenchymal stem cells (MSCs) derived from bone marrow (BM), adipose tissue (AT),
      umbilical cord blood (CB), and umbilical cord tissue (CT) are increasingly being
      used to treat equine inflammatory and degenerative lesions. MSCs modulate the
      immune system in part through mediator secretion. Animal species and MSC tissue
      of origin are both important determinants of MSC function. In spite of widespread
      clinical use, how equine MSCs function to heal tissues is fully unknown. In this
      study, MSCs derived from BM, AT, CB, and CT were compared for their ability to
      inhibit lymphocyte proliferation and secrete mediators in response to activation.
      Five MSC lines from each tissue were isolated. Lymphocyte proliferation was
      assessed in a mixed leukocyte reaction, and mediator secretion was determined by
      ELISA. Regardless of tissue of origin, quiescent MSCs did not alter lymphocyte
      proliferation or secrete mediators, except for transforming growth factor-beta
      (TGF-beta1). When stimulated, MSCs of all tissue types decreased lymphocyte
      proliferation, increased prostaglandin (PGE(2)) and interleukin-6 (IL-6)
      secretion, and decreased production of tumor necrosis factor-alpha (TNF-alpha)
      and interferon-gamma (IFN-gamma). BM-MSCs and CB-MSCs also produced nitric oxide
      (NO), while AT-MSCs and CT-MSCs did not. Equine MSCs did not produce indoleamine
      2,3-dioxygenase (IDO). These data suggest that activated equine MSCs derived from
      BM, AT, CT, and CB secrete high concentration of mediators and are similar to
      MSCs from rodents and humans in their immunomodulatory profiles. These findings
      have implication for the treatment of inflammatory lesions dominated by activated
      lymphocytes and TNF-alpha and IFN-gamma in vivo.

PMID- 23152952
TI  - A biosensor fabricated by incorporation of a redox mediator into a carbon
      nanotube/nafion composite for tyrosinase immobilization: detection of
      matairesinol, an endocrine disruptor.
AB  - An electrochemical matairesinol biosensor was fabricated by immobilizing
      tyrosinase on a poly(thionine)/nafion/multi-walled carbon nanotube composite
      film. A polymeric film of the redox dye thionine enables the stable
      immobilization of tyrosinase while acting as a mediator for the enzymatic process
      has been incorporated into the carbon nanotube/nafion composite film. The
      immobilization method is based on crosslinking of the tyrosinase layer with an
      electropolymerized film of poly(thionine). The good homogenization of the
      electron conductor CNTs in the integrated films provides the possibility of a
      three-dimensional electron conductive network. The biosensor was characterized by
      electrochemical impedance spectroscopy and electrochemical characterization. The
      composite electrode exhibits catalytic activity, high sensitivity, stability and
      is applicable over a wide range of concentrations from 180 nM to 4.33 MUM with a
      detection limit (LOD) of 37 nM. The obtained results suggest that the developed
      sensor can be successfully used for the determination of phenolic endocrine
      disruptors over a concentration range covering their environmental levels.

PMID- 23152953
TI  - Sub-cellular spectrochemical imaging of isolated human corneal cells employing
      synchrotron radiation-based Fourier-transform infrared microspectroscopy.
AB  - Understanding stem cell (SC) biology remains challenging and one of the few human
      tissues within which their in situ location is well characterized is the cornea.
      Individual human corneal epithelial cells were isolated from biopsies of live
      tissues using fluorescence-activated cell sorting (FACS); these were divided into
      putative SCs, transit-amplifying (TA) cells and terminally-differentiated (TD)
      cells. Employing synchrotron radiation-based Fourier-transform infrared (SR-FTIR)
      microspectroscopy with a focal plane array (FPA), sub-cellular spatial resolution
      analysis of unstained isolated cells was achieved as a consequence of the
      brilliance of a 12 collimated beams arrangement allowing rapid spectral
      acquisition. Infrared (IR) spectra were extracted and pre-processed. Subsequent
      categorization with multivariate analysis of IR spectra derived from FPA images
      was used to investigate biomolecular changes between classes. A progressive
      segregation in cell-specific spectral categories with differentiation from SC to
      TA cell to TD cell was noted. Multiple different absorption peaks that
      discriminated putative SCs, TA cells and TD cells across DNA, protein and lipid
      spectral regions were identified. DNA regions (1080 and 1225 cm(-1)) and some
      protein regions (1443 cm(-1)) primarily segregated SCs from TA cells and TD
      cells, whilst amide regions and lipids (1,550, 1650 and 1740 cm(-1)) segregated
      TA cells and TD cells. Scanning electron microscopy images verified the external
      phenotypic characteristics of the different isolated cell types. These findings
      highlight the applicability of SR-FTIR microspectroscopy towards distinguishing
      SCs, TA cells and TD cells, and suggest that cellular classification via
      traditional methods of immunolabelling can be greatly aided by the use of
      spectral biomarkers.

PMID- 23152955
TI  - Using droplet-based microfluidic technology to study the precipitation of a
      poorly water-soluble weakly basic drug upon a pH-shift.
AB  - The purpose of this study is to develop a droplet-based microfluidic device
      capable of monitoring drug precipitation upon a shift from gastric pH (pH 1.5) to
      intestinal pH (pH 6.5-7.0). The extent of precipitation occurring in droplets
      over time was measured using a novel on-chip laser scattering technique
      specifically developed for this study. The precipitation of ketoconazole, a
      poorly water-soluble basic drug, was investigated under different concentrations
      and pH values. It has been shown that the drug precipitates rapidly under
      supersaturation. Two water-soluble aqueous polymers, namely, polyvinylpyrrolidone
      (PVP) and hydroxypropylmethylcellulose (HPMC) have been evaluated as
      precipitation inhibitors. HPMC was shown to be the most potent precipitation
      inhibitor. It is envisaged that the microfluidic pH-shift method developed in
      this study would form a proof-of-concept study, towards the development of a high
      throughput method for screening pharmaceutical excipients/precipitation
      inhibitors.

PMID- 23152954
TI  - Disposable screen-printed sensors for the electrochemical detection of TNT and
      DNT.
AB  - Due to the heightened level of national security currently prevalent due to the
      possibility of terrorist incidents, highly portable, miniaturised and sensitive
      monitoring devices for trace levels of injurious materials, such as explosives
      are now of the upmost importance. One method that offers a possible route for the
      development of a detection system for such species is via an electrochemical
      regime, coupled to the use of disposable sensor technology. Within this study,
      the use of carbon screen-printed sensors for the detection and analysis of the
      classical explosive trinitrotoluene (TNT) and the related dinitrotoluene (DNT) is
      described, with the eventual objective to develop an inexpensive, accurate and
      sensitive detection system for trace quantities of explosives in field settings.
      Commercially available screen-printed carbon sensors have been used as the base
      platform for this investigation and the electrochemistry of both TNT and DNT
      studied at these surfaces. Two reductive peaks and one oxidative peak were
      observed for both analytes. The best linear fits and sensitivities were obtained
      using the reductive peak at -0.72 V vs. Ag/AgCl. A linear range from 1 to 200 MUM
      could be obtained for TNT and DNT in pH 7.0 phosphate buffer with limits of
      detection as low as 0.4 MUM (TNT) and 0.7 MUM (DNT). A second system which
      utilised the addition of the enzyme, nitroreductase, and the coenzyme, NADPH,
      into the solution matrix prior to electrochemical interrogations with screen
      printed carbon electrodes was found to increase the resulting signal magnitude at
      the oxidation peak at +0.3 V, improving the performance of the sensor at these
      values.

PMID- 23152956
TI  - Metabolomics study on the hepatoprotective effect of scoparone using ultra
      performance liquid chromatography/electrospray ionization quadruple time-of
      flight mass spectrometry.
AB  - Scoparone is an important constituent of Yinchenhao (Artemisia annua L.), a
      famous medicinal plant, and displayed bright prospects in the prevention and
      therapy of liver injury. However, the precise molecular mechanism of
      hepatoprotective effects has not been comprehensively explored. Here,
      metabolomics techniques are the comprehensive assessment of endogenous
      metabolites in a biological system and may provide additional insight into the
      mechanisms. The present investigation was designed to assess the effects and
      possible mechanisms of scoparone against carbon tetrachloride-induced liver
      injury. Ultra-performance liquid chromatography/electrospray ionization quadruple
      time-of-flight mass spectrometry (UPLC/ESI-Q-TOF/MS) combined with pattern
      recognition approaches including principal component analysis (PCA) and partial
      least squares-discriminant analysis (PLS-DA) were integrated to discover
      differentiating metabolites. Results indicate five ions in the positive mode as
      differentiating metabolites. Functional pathway analysis revealed that the
      alterations in these metabolites were associated with primary bile acid
      biosynthesis, pyrimidine metabolism. Of note, scoparone has a potential
      pharmacological effect through regulating multiple perturbed pathways to the
      normal state. Our findings also showed that the robust metabolomics techniques
      are promising for getting biomarkers and clarifying mechanisms of disease,
      highlighting insights into drug discovery.

PMID- 23152958
TI  - Nickel-catalyzed decyanation of inert carbon-cyano bonds.
AB  - Nickel catalyzed decyanation of aryl and aliphatic cyanides with hydrosilane as
      the hydride source has been developed. This method is easy to handle, scalable
      and can be carried out without a glove box. The method has been applied in the
      cyanide directed functionalization reaction and alpha-substitution of benzyl
      cyanide.

PMID- 23152960
TI  - The menopausal transition does not appear to accelerate age-related increases in
      arterial stiffness.
AB  - OBJECTIVE: Arterial stiffness is an independent marker of cardiovascular risk
      that increases with age, hypertension, diabetes and hyperlipidemia, both for men
      and women (although more pronounced in women). This study was designed to
      establish whether menopause augments the age-dependent change. METHODS: The study
      evaluated pulse wave analysis and pulse wave velocity using applanation tonometry
      in 468 women (aged 40-80 years) sampled from the general population. In multiple
      linear regression models, age was the predominant correlate of increasing aortic
      augmentation pressure (p < 0.0001), augmentation index (p < 0.0001), augmentation
      index adjusted to a heart rate of 75 beats/min (p < 0.0001) and carotid-femoral
      pulse wave velocity (p < 0.0001). RESULTS: Analysis of covariance showed no
      significant difference in adjusted mean of augmentation pressure, augmentation
      index or pulse wave velocity between menopause groups (pre-, peri-,
      postmenopause). Adjusted means of augmentation pressure and pulse wave velocity
      were comparable between women on hormone therapy (n = 130) and non-users (n =
      338). CONCLUSIONS: The results of the present study challenge the assertion by
      some researchers that menopause accelerates age-dependent changes in arterial
      stiffness.

PMID- 23152959
TI  - Polyelectrolyte-assisted transconformation of a stem-loop DNA.
AB  - A cationic copolymer triggered dimerization of a self-complementary stem-loop
      DNA. The dimerization was faster than spontaneous dissociation of the dimer.
      Reversible transformation between stem-loop and dimer structures was driven by
      switching on/off copolymer activity.

PMID- 23152957
TI  - An expedient synthesis of fused heteroacenes bearing a pyrrolo[3,2-b]pyrrole
      core.
AB  - Two linear fused heteroacenes bearing a pyrrolo[3,2-b]pyrrole core have been
      synthesized via a novel reductive ring closure methodology in three steps and in
      good overall yield. Preliminary OFET results showed that dinaphtho[2,3-b:2',3'
      f]pyrrolo[3,2-b]pyrrole (DNPP) is a potential candidate for organic electronics.

PMID- 23152961
TI  - Overexpression of the phosphatidylinositol synthase gene (ZmPIS) conferring
      drought stress tolerance by altering membrane lipid composition and increasing
      ABA synthesis in maize.
AB  - Phosphatidylinositol (PtdIns) synthase is a key enzyme in the phospholipid
      pathway and catalyses the formation of PtdIns. PtdIns is not only a structural
      component of cell membranes, but also the precursor of the phospholipid signal
      molecules that regulate plant response to environment stresses. Here, we obtained
      transgenic maize constitutively overexpressing or underexpressing PIS from maize
      (ZmPIS) under the control of a maize ubiquitin promoter. Transgenic plants were
      confirmed by PCR, Southern blotting analysis and real-time RT-PCR assay. The
      electrospray ionization tandem mass spectrometry (ESI-MS/MS)-based lipid
      profiling analysis showed that, under drought stress conditions, the
      overexpression of ZmPIS in maize resulted in significantly elevated levels of
      most phospholipids and galactolipids in leaves compared with those in wild type
      (WT). At the same time, the expression of some genes involved in the phospholipid
      metabolism pathway and the abscisic acid (ABA) biosynthesis pathway including
      ZmPLC, ZmPLD, ZmDGK1, ZmDGK3, ZmPIP5K9, ZmABA1, ZmNCED, ZmAAO1, ZmAAO2 and ZmSCA1
      was markedly up-regulated in the overexpression lines after drought stress.
      Consistent with these results, the drought stress tolerance of the ZmPIS sense
      transgenic plants was enhanced significantly at the pre-flowering stages compared
      with WT maize plants. These results imply that ZmPIS regulates the plant response
      to drought stress through altering membrane lipid composition and increasing ABA
      synthesis in maize.

PMID- 23152964
TI  - Towards in silico identification of the human ether-a-go-go-related gene channel
      blockers: discriminative vs. generative classification models.
AB  - HERG potassium channels have a critical role in the normal electrical activity of
      the heart. The blockade of hERG channels in heart cells can result in a
      potentially fatal disorder called long QT syndrome. HERG channels can be blocked
      by compounds with diverse structures belonging to several drug classes. Presented
      herein are generative (Generative Topographic Maps) and discriminative (Support
      Vector Machines) classification models to categorize the compounds in silico into
      active and inactive classes by using different types of descriptors. The
      predictive performance of discriminative and generative classification models has
      been compared. Here, the possibility of using Generative Topographic Maps as an
      approach for applicability domain analysis and to generate probability-based
      descriptors was demonstrated to our knowledge for the first time. Comparison of
      obtained results with the models developed by other teams on the same data set
      has been performed.

PMID- 23152963
TI  - Primary scene responses by Helicopter Emergency Medical Services in New South
      Wales Australia 2008-2009.
AB  - BACKGROUND: Despite numerous studies evaluating the benefits of Helicopter
      Emergency Medical Services (HEMS) in primary scene responses, little information
      exists on the scope of HEMS activities in Australia. We describe HEMS primary
      scene responses with respect to the time taken, the distances travelled relative
      to the closest designated trauma hospital and the receiving hospital; as well as
      the clinical characteristics of patients attended. METHODS: Clinical service data
      were retrospectively obtained from three HEMS in New South Wales between July
      2008 and June 2009. All available primary scene response data were extracted and
      examined. Geographic Information System (GIS) based network analysis was used to
      estimate hypothetical ground transport distances from the locality of each
      primary scene response to firstly the closest designated trauma hospital and
      secondly the receiving hospital. Predictors of bypassing the closest designated
      trauma hospital were analysed using logistic regression. RESULTS: Analyses
      included 596 primary missions. Overall the HEMS had a median return trip time of
      94min including a median of 9min for activation, 34min travelling to the scene,
      30min on-scene and 25min transporting patients to the receiving hospital. 72% of
      missions were within 100km of the receiving hospital and 87% of missions were in
      areas classified as 'major cities' or 'inner regional'. The majority of incidents
      attended by HEMS were trauma-related, with road trauma the predominant cause
      (44%). The majority of trauma patients (81%) had normal physiology at HEMS
      arrival (RTS = 7.84). We found 62% of missions bypassed the closest designated
      trauma hospital. Multivariate predictors of bypass included: age; presence of
      spinal or burns trauma; the level of the closest designated trauma hospital; the
      transporting HEMS. CONCLUSION: Our results document the large distances travelled
      by HEMS in NSW, especially in rural areas. The high proportion of HEMS missions
      that bypass the closest designated trauma hospital is a seldom mentioned benefit
      of HEMS transport. These results along with the characteristics of patients
      attended and the time HEMS take to complete primary scene responses are useful in
      understanding the benefit HEMS provides and the services it replaces.

PMID- 23152965
TI  - Patterns of referral to a gender identity service for children and adolescents
      (1976-2011): age, sex ratio, and sexual orientation.

PMID- 23152966
TI  - Controversies in the diagnosis and treatment of paraphilias.

PMID- 23152962
TI  - Efficacy and tolerability of peg-only laxative on faecal impaction and chronic
      constipation in children. A controlled double blind randomized study vs a
      standard peg-electrolyte laxative.
AB  - BACKGROUND: PEG-based laxatives are considered today the gold standard for the
      treatment of constipation in children. PEG formulations differ in terms of
      composition of inactive ingredients which may have an impact on acceptance,
      compliance and adherence to treatment. We therefore compared the efficacy,
      tolerability, acceptance and compliance of a new PEG-only formulation compared to
      a reference PEG-electrolyte (PEG-EL) formulation in resolving faecal impaction
      and in the treatment of chronic constipation. METHODS: Children aged 2-16 years
      with functional chronic constipation for at least 2 months were randomized to
      receive PEG-only 0.7 g/kg/day in 2 divided doses or 6.9 g PEG-EL 1-4 sachets
      according to age for 4 weeks. Children with faecal impaction were randomized to
      receive PEG-only 1.5/g/kg in 2 divided doses until resolution or for 6 days or
      PEG-EL with an initial dose of 4 sachets and increasing 2 sachets a day until
      resolution or for 7 days. RESULTS: Ninety-six children were randomized into the
      study. Five patients withdrew consent before starting treatment. Three children
      discontinued treatment for refusal due to bad taste of the product (1 PEG-only, 2
      PEG-EL); 1 (PEG-EL) for an adverse effect (abdominal pain). Intent-to-treat
      analysis was carried out in 49 children in the PEG-only group and 42 in the PEG
      EL group.No significant differences were observed between the two treatment
      groups at baseline.Adequate relief of constipation in terms of normalized
      frequency and painless defecation of soft stools was achieved in all patients in
      both groups. The number of stools/week was 9.2 +/- 3.2 (mean +/- SD) in the PEG
      only group and 7.8 +/- 2.4 in the PEG-EL group (p = 0.025); the number of days
      with stool was 22.4 +/- 5.1 in the PEG-only group and 19.6 +/- 7.2 in the PEG-EL
      group (p = 0.034).In the PEG-only group faecaloma resolution was observed in 5
      children on the second day and in 2 children on the third day, while in the PEG
      EL group it was observed in 2 children on the second day, in 3 children on the
      third day and in 1 child on the fifth day.Only 2 patients reported mild treatment
      related adverse events: 1 child in the PEG-only group had diarrhoea and vomiting
      and 1 child in the PEG-EL group had abdominal pain requiring treatment
      discontinuation. The PEG-only preparation was better tolerated as shown by the
      lower frequency of nausea than in the PEG-EL group.In the PEG-only group, 96% of
      patients did not demonstrate any difficulties associated with treatment, as
      compared with 52% of patients in the PEG-EL group (p < 0.001). Also, the PEG-only
      formulation taste was better than that of PEG-EL (p < 0.001). The difference
      between the percentage of subjects who took > 80% of the prescribed dose was in
      favour of the PEG-only group (98% vs. 88%), though it did not reach a
      conventional statistical level (p = 0.062). CONCLUSION: PEG-only was better
      tolerated and accepted than PEG-EL in children with chronic constipation. At the
      higher PEG doses recommended by the manufactures children in the PEG-only group
      had higher and more regular soft stool frequency than PEG-EL.

PMID- 23152967
TI  - Historical revolutions in sex therapy: a critical examination of men's sexual
      dysfunctions and their treatment.
AB  - History, recent and ancient, presents innumerable methods intended to ensure or
      restore male sexual performance. Although these methods have regularly claimed to
      be "revolutionary," they have often been remarkably similar, and of questionably
      efficacy. This article provides a critical account of key historical trends in
      the treatment of male sexual dysfunctions in order to contextualize and critique
      the current treatment field. The author uses historical analysis to contextualize
      contemporary sex therapy techniques, arguing that even clinically verified
      contemporary revolutions, such as the advent of Viagra and similar drugs, may not
      present broadly efficacious standalone cures. Using critical historical analysis
      to illustrate the limitations of single-method treatments, the article argues for
      the value of comprehensive, biopsychosocial therapy methods. A common tendency-
      to seek a 'magic bullet' solution to sexual dysfunctions--is apparent throughout
      history, the author argues. While Viagra differs biomedically from historical
      treatments, it may appeal to the same logic, raising the question of whether it
      constitutes a truly revolutionary development in treatment. The article concludes
      with a set of recommendations regarding the implementation of biopsychosocial
      practice in sex therapy.

PMID- 23152968
TI  - "There's a man in my bed": the first experience of sex among Modern-Orthodox
      newlyweds in Israel.
AB  - The first experience of sex is a significant life event for men and women.
      Studies investigating first-time sex focus largely on relationships at a young
      age and among teenagers, whereas studies of that experience in the context of
      marriage are extremely sparse and focus mainly on clinical population of
      unconsummated marriage. The authors explore the individual and mutual emotional
      effect of first-time intercourse among Modern-Orthodox newlywed couples in
      Israel. In-depth interviews with 36 men and women during their first year of
      marriage revealed unique challenges and difficulties related to sexuality in
      general and to first sex experience in particular. The findings indicate that
      first sexual intercourse is experienced by men and women as associated with
      emotional and behavioral difficulties, which appear to be rooted in the
      traditional nature of the religious Modern-Orthodox society in Israel. The
      authors explore reasoning and justifications for these challenges and detail
      different coping strategies-of the individual and of the couple. The findings
      might be relevant for other traditional societies in which couples experience sex
      only after marriage. The findings might also support professionals and sex
      therapists in addressing newlywed couples' needs in similar traditional
      populations.

PMID- 23152969
TI  - A population-based study investigating the association between sexual and
      relationship satisfaction and psychological distress among heterosexuals.
AB  - This study examined whether sexual/relationship satisfaction are differentially
      associated with mental health issues. Using data from a population-based computer
      assisted telephone survey, the authors included in this study 3,800 respondents
      who had a regular heterosexual partner. The authors used 2 methods of scoring the
      K6 to produce measures of moderate psychological distress and serious
      psychological distress. Overall, 8.8% of men and 12.1% of women were classified
      as having moderate psychological distress, whereas 1.6% of men and 3.2% of women
      were classified as currently experiencing serious psychological distress. The
      association between satisfaction and mental health was influenced by sex and the
      severity of the mental health issue but not by type of satisfaction. After
      adjusting for demographic differences in mental health, low ratings of
      sexual/relationship satisfaction were both consistently associated with higher
      levels of moderate psychological distress in men and women and higher proportions
      of serious psychological distress in men. Although women may be able to resolve
      their satisfaction issues during less severe stages of psychological distress,
      for men there was a strong association between low sexual/relationship
      satisfaction and serious psychological distress.

PMID- 23152974
TI  - Work-related musculoskeletal discomfort of dairy farmers and employed workers.
AB  - BACKGROUND: Dairy farming is physically demanding and associated with a high
      frequency of musculoskeletal disorders (MSD). This study investigated and
      compared work-related MSD, ergonomic work factors and physical exertion in
      farmers and employed farm workers on dairy farms in Sweden. METHODS: The study
      comprised 66 dairy farmers, and 37 employed dairy farm workers. A modified
      version of the general Standardised Nordic Questionnaire was used for analyses of
      perceived MSD in nine different parts of the body. Perceived physical discomfort
      was assessed using questions concerning ergonomic work factors. A rating scale
      was used for analyses of perceived physical exertion. Information about
      participant demographics was also collected. The response rate amounted to 70%.
      RESULTS: The most frequently reported MSD in farmers and farm workers were
      located in the lower back (50% and 43%, respectively) and the shoulders (47% and
      43%, respectively). MSD were also frequently reported in the neck (33%) among
      farmers, and in the hands/wrist (41%) among farm workers. MSD in the elbows (23%)
      and feet (21%) were significantly more frequently reported by farmers than farm
      workers (5%). Female farmers and farm workers both reported significantly higher
      frequencies of MSD in the neck (48% and 56%, respectively) and hands/wrists (44%
      and 61%, respectively) than their male colleagues (24% and 5%; 10% and 21%,
      respectively). In addition, female farm workers had significantly higher reported
      frequencies of MSD in the upper and lower back (39% and 61%, respectively) than
      their male counterparts (5% and 26%, respectively). Milking was perceived as a
      weakly to moderately physically demanding work task. Repetitive and monotonous
      work in dairy houses was the ergonomic work factor most frequently reported as
      causing physically discomfort among farmers (36%) and farm workers (32%),
      followed by lifting heavy objects (17% and 27%, respectively). Female workers had
      significantly more reported discomfort from repetitive and monotonous work than
      their male counterparts (50% and 16%, respectively). CONCLUSION: Despite the
      technical developments on modern dairy farms, there is still a high prevalence of
      MSD and discomfort from ergonomic work factors, particularly among female
      workers.

PMID- 23152975
TI  - Socio-economic risk factors for injuries in Swedish children and adolescents: a
      national study over 15 years.
AB  - Few studies have assessed if Sweden's injury prevention work has been equally
      effective for children of different socio-economic backgrounds. The goal of this
      paper is to review the country's injury rates for children over time, stratified
      by socio-economic status (SES), to see if the effects are similar across SES
      levels. This study employs a retrospective case-control study design, using data
      from the hospitalisation records of 51,225 children, which were linked to family
      socio-economic data. Children and adolescents in families receiving social
      welfare benefits, and those living with single parents and mothers with less
      education had higher risks of injuries leading to hospitalisation. The population
      based safety work over the past decades seems to have had only minor effects on
      reducing the impact of socio-economic based difference in injury risks to younger
      Swedes.

PMID- 23152976
TI  - Temperature and humidity influences on inactivation kinetics of enteric viruses
      on surfaces.
AB  - Norovirus (NoV) and hepatitis A virus (HAV) are pathogenic enteric viruses
      responsible for public health concerns worldwide. The viral transmission occurs
      through fecally contaminated food, water, fomites, or direct contact. However,
      the difficulty in cultivating these viruses makes it a challenge to characterize
      the resistance to various environmental stresses. In this study, we characterized
      the inactivation rates of murine norovirus (MNV), MS2, and HAV on either lacquer
      coating rubber tree wood or stainless steel under different temperature and
      relative humidity (RH) conditions. The viruses were analyzed at temperatures of
      15  degrees C, 25  degrees C, 32  degrees C, and 40  degrees C and at RHs of 30%,
      50%, and 70% for 30 days. Overall, they survived significantly longer on wood
      than on steel at lower temperature (P < 0.05). The inactivation rate of MS2 and
      MNV increased at higher RH levels, whereas HAV survived the best at a medium RH
      level (50%). The effect of RH was significant only for MS2 (P < 0.05). MS2
      persisted longest under all of the environmental conditions examined. Both a
      linear and a nonlinear Weibull model were used to describe the viral inactivation
      data in this study. The data produced a better fit to the survival curves that
      were predicted by the Weibull model.

PMID- 23152970
TI  - MDR1 in paroxetine-induced sexual dysfunction.
AB  - Paroxetine-induced sexual dysfunction represents a frequent treatment
      complication of otherwise efficient antidepressants. The genetic polymorphism of
      pharmacokinetic genes may contribute to the occurrence of such dysfunctions. This
      study presents the effect of MDR1 gene polymorphisms on sexual function in 18
      women with bulimia nervosa, 18 women with anxiety disorders, and 19 healthy
      control subjects. It also deals with the relation between MDR1 gene polymorphisms
      and paroxetine-induced sexual dysfunction. The results demonstrated that MDR1
      G2677T/A gene polymorphism allele carriers treated with paroxetine presented with
      difficulties with orgasm (p = .008) and lubrication (p < .001).

PMID- 23152977
TI  - General and biomimetic approach to biopolymer-functionalized graphene oxide
      nanosheet through adhesive dopamine.
AB  - Graphene oxide (GO), reduced graphene oxide (rGO), and their derivatives are
      investigated for various biomedical applications explosively. However, the
      defective biocompatibility was also recognized, which restricted their potential
      applications as biomaterials. In this study, a facile biomimetic approach for
      preparation of biopolymer adhered GO (rGO) with controllable 2D morphology and
      excellent biocompatibility was proposed. Mussel-inspired adhesive molecule
      dopamine (DA) was grafted onto heparin backbone to obtain DA grafted heparin (DA
      g-Hep) by carbodiimide chemistry method; then, DA-g-Hep was used to prepare
      heparin-adhered GO (Hep-a-GO) and heparin-adhered rGO (Hep-a-rGO). The obtained
      heparin-adhered GO (rGO) showed controllable 2D morphology, ultrastable property
      in aqueous solution, and high drug and dye loading capacity. Furthermore, the
      biocompatibility of the heparin-adhered GO (rGO) was investigated using human
      blood cells and human umbilical vein endothelial cells, which indicated that the
      as-prepared heparin-adhered GO (rGO) exhibited ultralow hemolysis ratio (lower
      than 1.2%) and high cell viability. Moreover, the highly anticoagulant
      bioactivity indicated that the adhered heparin could maintain its biological
      activity after immobilization onto the surface of GO (rGO). The excellent
      biocompatibility and high bioactivity of the heparin-adhered GO (rGO) might
      confer its great potentials for various biomedical applications.

PMID- 23152978
TI  - New insights into formation of trivalent actinides complexes with DTPA.
AB  - Complexation of trivalent actinides with DTPA (diethylenetriamine pentaacetic
      acid) was studied as a function of pcH and temperature in (Na,H)Cl medium of 0.1
      M ionic strength. Formation constants of both complexes AnHDTPA(-) and AnDTPA(2-)
      (where An stands for Am, Cm, and Cf) were determined by TRLFS, CE-ICP-MS,
      spectrophotometry, and solvent extraction. The values of formation constants
      obtained from the different techniques are coherent and consistent with
      reinterpreted literature data, showing a higher stability of Cf complexes than Am
      and Cm complexes. The effect of temperature indicates that formation constants of
      protonated and nonprotonated complexes are exothermic with a high positive
      entropic contribution. DFT calculations were also performed on the An/DTPA
      system. Geometry optimizations were conducted on AnDTPA(2-) and  AnHDTPA(-)
      considering all  possible protonation sites. For both complexes, one and two
      water molecules in the first coordination sphere of curium were also considered.
      DFT calculations indicate that the lowest energy structures correspond to
      protonation on oxygen that is not involved in An-DTPA bonds and that the
      structures with two water molecules are not stable.

PMID- 23152979
TI  - The dynamics of polymer bridge formation and disruption and its effect on the
      bulk rheology of suspensions.
AB  - Bridge-flocculated colloidal gels are used in many important processes and
      products such as gel casting for advanced ceramics, precursor inks for 3D
      printing, and waste treatment strategies. An important aspect of polymer bridged
      gels that makes them excellent candidates for these applications is the precise
      control it affords for control of rheological properties. Recent studies have
      shown that adhesion between bridged surfaces increases with time as the number of
      polymer bridges formed grows. However, the consequences of the dynamics of these
      processes toward bulk rheological properties have not been studied. Here we
      investigate the link between the dynamics of polymer bridging and disruption and
      bulk rheology in dense colloidal silica particle suspensions flocculated by
      polyethylene oxide (PEO). Microscale pull-off force measurements using atomic
      force microscope (AFM) show that upon repeated disruption and establishment of
      bridged contact, the adhesion between the surfaces is reduced. During contact
      disruption, the polymer chains bridging the two surfaces are stretched leading to
      chain scission. On the re-establishment of contact, these fragmented polymer
      chains are unable to fully re-establish the adhesion. Macroscale measurements
      using oscillatory rheology show that this reduced adhesion results in reduction
      of both the storage modulus and the yield stress. If the slurry is subjected to
      high shear for long periods, polymer chain scission is amplified, and the
      fragmented polymer chains are unable to bridge the particles again, resulting in
      free-flowing slurries.

PMID- 23152981
TI  - Pediatric musculoskeletal examination for juvenile arthritis.

PMID- 23152980
TI  - The use of individual cut points from treadmill walking to assess free-living
      moderate to vigorous physical activity in obese subjects by accelerometry: is it
      useful?
AB  - BACKGROUND: Variation in counts between subjects at a given speed or work rate
      are the most important source of error in physical activity (PA) measurements
      with accelerometers. The aim of this study was to explore how the use of
      individual accelerometer cut points (ICPs) affected the analysis of PA field
      data. METHODS: We performed a treadmill calibration protocol to determine cut
      points for moderate to vigorous PA (MVPA) (>=3 metabolic equivalents) and
      assessed free-living PA in 44 severely obese subjects using the Actigraph GT1M
      accelerometer. We obtained cut points in 42 subjects (11 men, mean (standard
      deviation) of body mass index (BMI) 39.8 (5.7), age 43.2 (9.2) years), of whom 35
      had valid measurement of free-living PA (minutes of MVPA/day). Linear regression
      was used to analyze associations with the ICPs and time in MVPA/day. MVPA/day was
      also compared with values derived using a group cut point (GCP). RESULTS: Resting
      oxygen consumption (partial r = 0.74, p < .001), work economy (partial r = -0.76,
      p < .001) and BMI (partial r = 0.52, p = .001) explained 68.4% of the variation
      in the ICPs (F = 26.7, p < .001). The ICPs explained 79.1% of the variation in
      the minutes spent in MVPA/day. Moderate to vigorous PA/day derived from the ICPs
      vs. the GCP varied substantially (R2 = 14%, p = .023, coefficient of variation =
      45.1%). CONCLUSIONS: The results indicate that the use of ICPs had a strong
      influence on the PA level. Two thirds of the variation in the ICPs could be
      explained, however, a certain degree of measurement error will be present. Thus,
      we are not able to conclude with respect to the most appropriate procedure for
      analyzing time in MVPA.

PMID- 23152982
TI  - Myxofibrosarcoma of the sinus piriformis: case report and literature review.
AB  - Myxofibrosarcoma is a common sarcoma in the extremities of older people, but is
      rare in the head and neck region. Here, we report the case of a 42-year-old male
      patient in whom myxofibrosarcoma generated from the sinus piriformis.
      Histopathologically, the tumor was characterized by spindle cellular
      proliferation with moderate cellular density in fibromyxoid stroma.
      Immunohistochemically, the tumor cells showed positive reactivity for vimentin,
      Ki-67, smooth muscle actin, and CD34, but negative staining for S-100. Based on
      these results, the tumor was diagnosed as a low-grade myxofibrosarcoma. Resection
      of the tumor was performed via a transcervical approach. The patient's
      postoperative clinical course was uneventful and no local recurrence or distant
      metastasis has been found so far. The pathology, clinical characteristics, and
      treatment of myxofibrosarcoma are also reviewed.

PMID- 23152984
TI  - The influence of mammogram acquisition on the mammographic density and breast
      cancer association in the Mayo Mammography Health Study cohort.
AB  - INTRODUCTION: Mammographic density is a strong risk factor for breast cancer.
      Image acquisition technique varies across mammograms to limit radiation and
      produce a clinically useful image. We examined whether acquisition technique
      parameters at the time of mammography were associated with mammographic density
      and whether the acquisition parameters confounded the density and breast cancer
      association. METHODS: We examined this question within the Mayo Mammography
      Health Study (MMHS) cohort, comprised of 19,924 women (51.2% of eligible) seen in
      the Mayo Clinic mammography screening practice from 2003 to 2006. A case-cohort
      design, comprising 318 incident breast cancers diagnosed through December 2009
      and a random subcohort of 2,259, was used to examine potential confounding of
      mammogram acquisition technique parameters (x-ray tube voltage peak (kVp),
      milliampere-seconds (mAs), thickness and compression force) on the density and
      breast cancer association. The Breast Imaging Reporting and Data System four
      category tissue composition measure (BI-RADS) and percent density (PD) (Cumulus
      program) were estimated from screen-film mammograms at time of enrollment.
      Spearman correlation coefficients (r) and means (standard deviations) were used
      to examine the relationship of density measures with acquisition parameters.
      Hazard ratios (HR) and C-statistics were estimated using Cox proportional hazards
      regression, adjusting for age, menopausal status, body mass index and
      postmenopausal hormones. A change in the HR of at least 15% indicated
      confounding. RESULTS: Adjusted PD and BI-RADS density were associated with breast
      cancer (p-trends < 0.001), with a 3 to 4-fold increased risk in the extremely
      dense vs. fatty BI-RADS categories (HR: 3.0, 95% CI, 1.7 - 5.1) and the >= 25%
      vs. <= 5% PD categories (HR: 3.8, 95% CI, 2.5 - 5.9). Of the acquisition
      parameters, kVp was not correlated with PD (r = 0.04, p = 0.07). Although
      thickness (r = -0.27, p < 0.001), compression force (r = -0.16, p < 0.001), and
      mAs (r = -0.06, p = 0.008) were inversely correlated with PD, they did not
      confound the PD or BI-RADS associations with breast cancer and their inclusion
      did not improve discriminatory accuracy. Results were similar for associations of
      dense and non-dense area with breast cancer. CONCLUSIONS: We confirmed a strong
      association between mammographic density and breast cancer risk that was not
      confounded by mammogram acquisition technique.

PMID- 23152983
TI  - Staphylococcal leukotoxins trigger free intracellular Ca(2+) rise in neurones,
      signalling through acidic stores and activation of store-operated channels.
AB  - Headache, muscle aches and chest pain of mild to medium intensity are among the
      most common clinical symptoms in moderate Staphylococcus aureus infections, with
      severe infections usually associated with worsening pain symptoms. These
      nociceptive responses of the body raise the question of how bacterial infection
      impinges on the nervous system. Does S. aureus, or its released virulence
      factors, act directly on neurones? To address this issue, we evaluated the
      potential effects on neurones of certain bi-component leukotoxins, which are
      virulent factors released by the bacterium. The activity of four different
      leukotoxins was verified by measuring the release of glutamate from rat
      cerebellar granular neurones. The bi-component gamma-haemolysin HlgC/HlgB was the
      most potent leukotoxin, initiating transient rises in intracellular Ca(2+)
      concentration in cerebellar neurones and in primary sensory neurones from dorsal
      root ganglia, as probed with the Fura-2 Ca(2+) indicator dye. Using
      pharmacological antagonists of receptors and Ca(2+) channels, the variations in
      intracellular Ca(2+) concentration were found independent of the activation of
      voltage-operated Ca(2+) channels or glutamate receptors. Drugs targeting Sarco
      Endoplasmic Reticulum Ca(2+)-ATPase (SERCA) or H(+)-ATPase and antagonists of the
      store-operated Ca(2+) entry complex blunted, or significantly reduced, the
      leukotoxin-induced elevation in intracellular Ca(2+). Moreover, activation of the
      ADP-ribosyl cyclase CD38 was also required to initiate the release of Ca(2+) from
      acidic stores. These findings suggest that, prior to forming a pore at the plasma
      membrane, leukotoxin HlgC/HlgB triggers a multistep process which initiates the
      release of Ca(2+) from lysosomes, modifies the steady-state level of reticular
      Ca(2+) stores and finally activates the Store-Operated Calcium Entry complex.

PMID- 23152985
TI  - Participating in diagnostic experience: adults with neuropsychiatric disorders.
AB  - Abstract   Knowledge regarding neuropsychiatric disabilities has increased in
      recent years, resulting in an increasing number of adults requesting
      neuropsychiatric evaluation. The aim of this qualitative study was to describe
      adult clients' experiences of participating actively in a supportive assessment
      process in which they received a diagnosis of either autism spectrum disorder
      (ASD) and/or attention-deficit hyperactivity disorder (ADHD) and then received
      follow-up counselling, guidance, and compensatory resources that were immediate
      and directly integrated into the diagnostic experience. The Occupational
      Performance History Interview - Second Version (OPHI-II) was selected because it
      is client-centred. It measures how a significant life event affects a person's
      occupational identity, occupational competence, and interaction with the
      environment. The OPHI-II was administered to capture 15 participants' experiences
      of being diagnosed with ASD and/or ADHD as the significant life event of focus.
      Three categories were formed by using qualitative content analysis: (i)
      strengthened occupational identity; (ii) compensatory support enhances
      occupational competence, and (iii) effects of the social environment on
      relationships. Findings indicated that the diagnostic experience had
      transformative effects on participants' occupational identities, occupational
      competence, and ability to self-advocate for increased understanding and
      resources within their environments. The implications of these findings and
      future research are discussed.

PMID- 23152987
TI  - [Abdominal complications in patients with implanted mechanical cardiac support].
AB  - Patients with implanted mechanical cardiac support are exposed to the risk of
      various complications in the early postoperative period. Although thromboembolic
      and bleeding events occur most frequently in these patients, we cannot disregard
      other complications that can have a significant impact on the further development
      of the implanted patients condition. These include abdominal complications.
      Literature data show clearly that mortality in implanted patients who developed
      an abdominal complication is significantly higher than that in patients without
      postoperative abdominal complications.

PMID- 23152986
TI  - A high density recombination map of the pig reveals a correlation between sex
      specific recombination and GC content.
AB  - BACKGROUND: The availability of a high-density SNP genotyping chip and a
      reference genome sequence of the pig (Sus scrofa) enabled the construction of a
      high-density linkage map. A high-density linkage map is an essential tool for
      further fine-mapping of quantitative trait loci (QTL) for a variety of traits in
      the pig and for a better understanding of mechanisms underlying genome evolution.
      RESULTS: Four different pig pedigrees were genotyped using the Illumina
      PorcineSNP60 BeadChip. Recombination maps for the autosomes were computed for
      each individual pedigree using a common set of markers. The resulting genetic
      maps comprised 38,599 SNPs, including 928 SNPs not positioned on a chromosome in
      the current assembly of the pig genome (build 10.2). The total genetic length
      varied according to the pedigree, from 1797 to 2149 cM. Female maps were longer
      than male maps, with a notable exception for SSC1 where male maps are
      characterized by a higher recombination rate than females in the region between
      91-250 Mb. The recombination rates varied among chromosomes and along individual
      chromosomes, regions with high recombination rates tending to cluster close to
      the chromosome ends, irrespective of the position of the centromere. Correlations
      between main sequence features and recombination rates were investigated and
      significant correlations were obtained for all the studied motifs. Regions
      characterized by high recombination rates were enriched for specific GC-rich
      sequence motifs as compared to low recombinant regions. These correlations were
      higher in females than in males, and females were found to be more recombinant
      than males at regions where the GC content was greater than 0.4. CONCLUSIONS: The
      analysis of the recombination rate along the pig genome highlighted that the
      regions exhibiting higher levels of recombination tend to cluster around the ends
      of the chromosomes irrespective of the location of the centromere. Major sex
      differences in recombination were observed: females had a higher recombination
      rate within GC-rich regions and exhibited a stronger correlation between
      recombination rates and specific sequence features.

PMID- 23152988
TI  - [The development of surgical treatment in liver and biliary tract diseases].
AB  - INTRODUCTION: Surgical liver and biliary tract diseases remain to be among the
      most serious and the incidence of illnesses requiring surgical treatment has been
      increasing. It is therefore essential to consider the new possibilities of
      oncological and miniinvasive care, including ablation treatment, and to evaluate
      their importance and integration in the treatment system. MATERIAL AND METHODS:
      The article presents a retrospective analysis of three consecutive sets of
      patients from 1991-2011. Our monitoring focused primarily on bile duct lesions
      and on primary and secondary tumours of the liver. Assessments included the
      extent and method of the operation, neoadjuvant and adjuvant care, complications,
      lethality, and survival rate. RESULTS: Our study confirmed that the number of
      surgically treated secondary tumours (colorectal carcinoma metastases) rose by 9%
      as a result of downstaging (i.e., the combination of chemotherapy and oncological
      treatment or RFA) and the use of embolization via the portal vein and sequential
      resections. With no fundamental changes recorded in hepatocellular carcinoma
      treatment, resection or transplantation still appears to be the only curative
      treatment method. One-year survival is minimal without these procedures. We
      recorded a slight increase in the incidence of cholangiocarcinoma from 6 to
      10.3%. The results of extrahepatic and hepatic form resections range from 0 to
      90%, depending on the stage of the disease. Biliary duct lesions are treated more
      frequently at the time of laparoscopic surgery; they are diagnosed later or when
      stenosis has already developed, and hepaticojejunoanastomosis is the most widely
      applied procedure in treating the lesions. The authors indicate the ablation
      methods in hepatic and bile duct tumour treatment only when resection treatment
      is not possible. CONCLUSION: Surgical resection treatment in malignant diseases
      of the liver and biliary tract remains the primary treatment method with a high
      curative potential. Neoadjuvant combined treatment increases the eligibility of
      patients for such surgical procedures. In biliary tract lesions, we also regard
      the surgical approach as dominant. The overview of results for individual periods
      implies the necessity of interdisciplinary care in order to achieve better
      results in surgical management.

PMID- 23152989
TI  - [SILS appendectomy for acute appendicitis - two-year experience].
AB  - INTRODUCTION: The study aims to present our two-year experience with SILS (Single
      Incision Laparoscopic Surgery) appendectomy in patients operated on for acute
      appendicitis symptoms. The results obtained were analysed and then compared with
      patients operated by standard laparoscopy, as well as with data available from
      the published literature with emphasis on safety and advantages of a new
      operating technique. MATERIAL AND METHODS: A retrospective analysis of patients
      operated on at the Third Department of Surgery, Slovak Medical University, the
      Kosice-Saca Hospital, a.s., in the past two years was performed. Age, sex, BMI,
      length of operation, post-operative hospitalization period, occurrence of pre-
      and post-operative complications were evaluated. RESULTS: In the period from 1
      November 2009 to 31 October 2011, 116 patients were operated on by the authors,
      47 of them by the SILS technique. The group included 26 males and 21 females with
      average age of 37.13 years (18-80) and average BMI 26.3 kg/m2 (18-47.1). Average
      length of the operation was 54.81 minutes (30-100). The length of post-operative
      hospital stay was 3.83 days (2-6). An abscess in the surgical wound was found in
      three patients. One patient had to be reoperated due to a pericaecal abscessed
      hematoma. Incisional hernia was not observed in our group. CONCLUSION: Our
      results are comparable with the data from international published literature and
      confirm that the SILS appendectomy is a safe method and represents an appropriate
      alternative to the standard laparoscopic technique. It is suitable for surgeons
      with advanced experience in laparoscopy. Apart from the excellent cosmetic
      effect, other advantages or disadvantages in comparison with standard laparoscopy
      will require confirmation by prospective randomized studies.

PMID- 23152990
TI  - [Pharmacological influencing of abdominal aortic aneurysm model - animal
      experimental study, primary results].
AB  - INTRODUCTION: The aim of our work was to influence growth and histological
      changes in the wall of an experimentally induced aneurysm of the abdominal aorta
      in a large laboratory animal (domestic pig) by administering atorvastatin (3
      hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor). MATERIAL AND METHODS:
      Within the scope of the above mentioned experimental work, we compared the growth
      rate of the aneurysm between the group influenced by statin administration (n=14)
      and the group without any pharmacological treatment (n=13). We also compared
      histological changes in the structure of the aortic wall in both groups with
      aneurysm and the wall of the aorta without aneurysm (n=6). RESULTS: During the 4
      week follow-up, we did not prove a statistically significant difference in the
      growth rate of aneurysms between the above mentioned groups. The histological
      structure of the aneurysm walls, however, differed between the two groups. The
      structure of the wall in the group of animals influenced by statin administration
      resembled the structure of the aortic wall without aneurysm. CONCLUSION: The
      results presented demonstrate that statins do influence the composition of the
      aortic wall. In our opinion, the administration of statins could lead to changes
      resulting in a more stable aneurysmatic wall. We believe that patients with
      smaller aneurysms who are not indicated for surgery or endovascular treatment
      could be treated with statins. Stabilization of the aneurysmal wall could slow
      down the growth of the aneurysm and prevent its rupture.

PMID- 23152991
TI  - [Diverticulum of the greater curvature of the stomach as a cause of anaemia].
AB  - Gastric diverticula represent a rare pathological condition. They are usually
      asymptomatic and are often found only by accident during radiologic or endoscopic
      examination, or during autopsy. Their incidence is low and evenly distributed
      between men and women. Gastric diverticula are most frequently located on the
      posterior wall of the cardia and on the lesser curvature of the stomach. The
      authors present a case study of a 58-year-old patient with severe sideropenic
      anaemia, a marked weight loss and non-specific dyspeptic symptoms. The suspicion
      of a diverticulum was raised by a gastroenterologist during gastrofibroscopy and
      confirmed by a radiologist following a dynamic CT examination of the stomach. The
      diverticulum had an atypical location beneath the cardia on the greater
      curvature. The patient was indicated for surgery. During conventional laparotomy,
      resection of the diverticulum was performed using a linear stapler. The
      postoperative course was uneventful. Histology confirmed a false diverticulum.
      The patient is doing well, is asymptomatic, has put on 7 kg since the operation
      and her blood count is normal.

PMID- 23152992
TI  - [A giant gastrointestinal stromal tumour  - a case report].
AB  - Gastrointestinal stromal tumours represent a group of non-epithelial
      gastrointestinal tumours that have both benign and malignant character. Most
      frequently, they occur in the stomach and the intestine; however, as regards
      their overall incidence, they are rather infrequent tumour lesions. The present
      case report describes a rare bulky extragastrointestinal stromal tumour
      originating from the mesenterium in a young patient. Its anatomical and
      histological picture, diagnosis and treatment are described. Our work points to
      the necessity for physicians to also bear in mind the less likely options and
      highlights the role of surgery in the treatment of such voluminous findings.

PMID- 23152994
TI  - [Fracture dislocations of the ankle--new views on an old problem].

PMID- 23152995
TI  - [Classification of fracture dislocations of the ankle].

PMID- 23152996
TI  - [Injuries of the medial structures of the ankle].

PMID- 23152997
TI  - [Fractures of the posterior tibial margin in ankle fractures].

PMID- 23152998
TI  - [Suprasyndesmal screw in fracture dislocation of the ankle].

PMID- 23152999
TI  - The effect of polymerized placenta hemoglobin on renal ischemia/reperfusion
      injury.
AB  - The goal of this study was to investigate whether hemoglobin-based oxygen carrier
      (HBOC) attenuated ischemia/reperfusion (I/R)-induced kidney injury. Male SD rats
      were randomly divided into a sham group, I/R group, and HBOC group (injection of
      0.1 gHb/kg PolyPHb). The ischemia was induced by bilateral renal pedicle cross
      clamping for 45min. Then the clamp was released to allow 24h reperfusion. Without
      increasing blood pressure, PolyPHb reduced the blood urea nitrogen and creatinine
      in plasma and attenuated the tumor necrosis factor-alpha and interleukin-8 in
      kidney tissue. Therefore, our findings suggest that PolyPHb could reduce kidney
      injury after I/R injury, and this effect was probably associated with the
      depressed inflammatory response.

PMID- 23153000
TI  - The mediating role of social environmental factors in the associations between
      attachment styles and basic needs satisfaction.
AB  - The present study aimed to explore the mediating role of social factors on the
      associations between attachment styles and basic psychological needs satisfaction
      within two relational contexts. Athletes (N = 215) completed a multi-section
      questionnaire pertaining to attachment styles, basic needs satisfied within the
      coaching and the parental relational context, and such social factors as social
      support, interpersonal conflict, autonomy and controlling behaviours. Bootstrap
      mediation analysis revealed that the association between avoidant attachment
      style and basic needs satisfaction with the coach was mediated by social support
      and autonomy-related behaviours from the coach. The association between avoidant
      attachment style and basic needs satisfaction with the parent on the other hand
      was mediated by all social factors investigated. Finally, the association between
      anxious attachment style and basic needs satisfaction from the parent was
      mediated by conflict and controlling behaviours. Overall, the findings of the
      current study suggest that social factors play an important role in explaining
      the associations between attachment styles and basic needs satisfaction within
      two central relational contexts athletes operate in, and thus should be targeted
      in future interventions.

PMID- 23153001
TI  - Identifying symptom clusters during the menopausal transition: observations from
      the Seattle Midlife Women's Health Study.
AB  - OBJECTIVES: First, to explore the variability in how symptoms clustered together
      over the late reproductive stage, early and late menopausal transition (MT)
      stages, and early postmenopause; second, to determine whether the symptom factor
      structure of the preceding MT stage would predict the symptom factor structure of
      the MT stage immediately following. METHODS: The sample consisted of a subset of
      Seattle Midlife Women's Health Study participants who were in late reproductive
      or early or late menopausal transition stages or early postmenopause and provided
      self-reported data on symptoms experienced between 1990 and 2005. Principal
      components analysis was used to determine how symptoms clustered together across
      the stages. Variables predicting the symptom factor structure were analyzed by
      multiple regression. RESULTS: Principal components analysis with varimax rotation
      revealed different factor structures for each of the four stages. The three
      factor solution in the late reproductive stage explained a total of 54.9% of the
      variance. The four-factor solutions in the early and late menopausal transition
      stages and postmenopause explained a total of 56.5%, 59.3%, and 60.7%,
      respectively. CONCLUSIONS: This analysis revealed similar factor structures
      across the four stages in that each stage revealed a mood component, a vasomotor
      component, and a pain component. However, the symptoms differed somewhat in how
      they grouped from stage to stage. Regression analysis demonstrated that a
      relationship exists between the symptom factor structures across stages.
      Controlling for demographic and lifestyle variables, it was revealed that the
      symptom clusters at the early and late menopausal transition stages and early
      postmenopause were best predicted by the symptom factor structure of the previous
      stage.

PMID- 23153002
TI  - Is this a genesis in prenatal testing: genomic knowledge, risk or benefit?

PMID- 23153003
TI  - Psychological well-being and family satisfaction levels five years after being
      confirmed as a carrier of the Machado-Joseph disease mutation.
AB  - The present study on long-term outcome of presymptomatic testing for Machado
      Joseph disease (MJD) aimed to evaluate the psychological well-being and the
      familial satisfaction of subjects that 5 years prior received an unfavorable
      result in the predictive testing (PT). The study included 47 testees of Azorean
      origin (23 from the island of Flores and 24 from S. Miguel) that completed the
      fourth evaluation session of the MJD protocol, and undertook a neurological
      examination at the moment of participation in the study. Nearly 50% of testees
      were symptomatic at the time of the study. Psychological well-being of the 47
      participants was evaluated using the Psychological General Well-Being Index
      (PGWB). The family satisfaction scale by adjectives was applied to obtain
      information on family dynamics. The average PGWB score of the total participants
      was of 73.3, a value indicative of psychological well-being. Nearly half of the
      testees presented scores indicating psychological well-being, whereas scores
      indicating moderate (28.9%) or severe (23.7%) stress were found in the remaining.
      The average score in the PGWB scale was lower in symptomatic than in asymptomatic
      subjects; moreover, the distinct distribution of the well-being categories seen
      in the two groups shows an impact of the appearance of first symptoms on the
      psychological state. Motives for undertaking the test, provided 5 years prior,
      failed to show an impact in well-being. The average score for familial
      satisfaction was of 134, a value compatible with high familial satisfaction,
      which represented the most frequent category (59.6%). Results demonstrate that
      well-being and family satisfaction need to be monitored in confirmed carriers of
      the MJD mutation. The inclusion of acceptance studies, after PT, as well as the
      development of acceptance training actions, should be of major importance to
      anticipate the possibility of psychological damage.

PMID- 23153004
TI  - Evaluation of the association between the ADRA2A genetic polymorphisms and type 2
      diabetes in a Chinese Han population.
AB  - Alpha-2-adrenergic receptor (ADRA2A) is involved in the sympathetic nervous
      system and plays a role in the regulation of insulin secretion and lipolysis.
      Recent studies have indicated that the ADRA2A polymorphisms are associated with
      type 2 diabetes (T2DM) in Caucasians and African Americans. The present study
      aimed to evaluate the association between the ADRA2A polymorphisms and T2DM in a
      Chinese Han population. Two single-nucleotide polymorphisms (SNPs) rs521674 and
      rs553668 in the ADRA2A gene were genotyped in 2094 Chinese subjects (1042 T2DM
      patients and 1052 nondiabetic controls) by using the TaqMan allelic
      discrimination technique. A single-locus analysis indicated that SNP rs553668 was
      associated with T2DM (p=0.04). Further analysis indicated that the association of
      SNP rs553668 was found in T2DM patients with body mass index (BMI)<25 kg/m(2)
      (p=0.03), but not in the patients with BMI>=25 kg/m(2) (p=0.56). This association
      was still significant in a recessive model (p=0.01, odds ratio=0.68, 95%
      confidence interval=0.51-0.92). In conclusion, the present study provides
      evidence that the ADRA2A polymorphism, rs553668, is associated with lean T2DM
      patients in a Chinese Han population. Further investigation to explore the role
      of ADRA2A in the regulation of body weight has been taken into our consideration.

PMID- 23153006
TI  - Comparison of the caries-preventive effect of a glass ionomer sealant and
      fluoride varnish on newly erupted first permanent molars of children with and
      without dental caries experience.
AB  - PURPOSE: This longitudinal clinic study evaluated the effect of a glass ionomer
      sealant (GIS) and a fluoride varnish (FV) in the prevention of dental decay on
      newly erupted permanent molars of children with and without caries experience.
      MATERIALS AND METHODS: Eighty children, aged 6-8 years, with all four newly
      erupted first permanent molars, were divided into two groups. Group 1 consisted
      of 53 children without caries experience and group 2 consisted of 27 children
      with dental caries experience. Permanent molars of the right side were sealed
      with GIS and the fluoride varnish was applied on the other two permanent first
      molars. Evaluation of GIS retention and the effectiveness of both materials in
      the prevention of dental caries were performed after 6, 12 and 18 months.
      RESULTS: After 18 months, of the 299 teeth, 271 (91%) showed no caries lesions
      and 28 presented caries lesions (9%). Teeth sealed with GIS had more carious
      lesions (15) than teeth with fluoride varnish (13). Most of the teeth (70%) that
      presented carious lesions were in group 2. Of the 138 sealed teeth, only one
      showed GIS to be totally present, 95 were partially present and 42 teeth were
      absent. CONCLUSION: The caries-preventive effect was very similar between both
      treatments. The presence of dental caries prevailed in the children with caries
      experience.

PMID- 23153005
TI  - Afebrile spotted fever group Rickettsia infection after a bite from a Dermacentor
      variabilis tick infected with Rickettsia montanensis.
AB  - Several spotted fever group rickettsiae (SFGR) previously believed to be
      nonpathogenic are speculated to contribute to infections commonly misdiagnosed as
      Rocky Mountain spotted fever (RMSF) in the United States, but confirmation is
      difficult in cases with mild or absent systemic symptoms. We report an afebrile
      rash illness occurring in a patient 4 days after being bitten by a Rickettsia
      montanensis-positive Dermacentor variabilis tick. The patient's serological
      profile was consistent with confirmed SFGR infection.

PMID- 23153007
TI  - Bromine- and chlorine-containing aeruginosins from Microcystis aeruginosa bloom
      material collected in Kibbutz Geva, Israel.
AB  - Five new natural products, aeruginosins GE686 (1), GE766 (2), GE730 (3), GE810
      (4), and GE642 (5), were isolated along with four known aeruginosins, 98C, 101,
      KY642, and DA688, from bloom material of the cyanobacterium Microcystis
      aeruginosa collected from a fish pond in Kibbutz Geva, Israel, in August 2007.
      Their structures were elucidated by a combination of various spectroscopic
      techniques, primarily NMR and MS, while the absolute configurations of the
      stereogenic centers were determined by Marfey's and chiral-phase HPLC methods.
      Two of the new aeruginosins, aeruginosins GE686 (1) and GE766 (2), contain the
      unprecedented d-m-Br-m'-Cl-p-hydroxyphenyllactic acid derivative. The structures
      and biological activities of the five new metabolites are described.

PMID- 23153008
TI  - In-depth membrane proteomic study of breast cancer tissues for the generation of
      a chromosome-based protein list.
AB  - The Chromosome-centric Human Proteome Project (C-HPP) aims to define all proteins
      encoded in each chromosome and especially to identify proteins that currently
      lack evidence by mass spectrometry. The C-HPP also prioritizes particular protein
      subsets such as membrane proteins, post-translational modifications, and low
      abundance proteins. In this study, we aimed to generate deep profiling of the
      membrane proteins of human breast cancer tissues on a chromosome-by-chromosome
      basis using shotgun proteomics. We identified 7092 unique proteins using membrane
      fractions isolated from pooled breast cancer tissues with high confidence. A
      total of 3282 proteins were annotated as membrane proteins by Gene Ontology
      analysis, which covered 45% of the membrane proteins predicted in 20,859 protein
      coding genes. Furthermore, we were able to identify 851 membrane proteins that
      currently lack evidence by mass spectrometry in neXtProt. Our results will
      contribute to the accomplishment of the primary goal of the C-HPP in identifying
      so-called "missing proteins" and generating a whole protein catalog for each
      chromosome.

PMID- 23153010
TI  - Spectroscopic properties of multilayered gold nanoparticle 2D sheets.
AB  - We report the fabrication technique and optical properties of multilayered two
      dimensional (2D) gold nanoparticle sheets ("Au nanosheet"). The 2D crystalline
      monolayer sheet composed of Au nanoparticles shows an absorption peak originating
      from a localized surface plasmon resonance (LSPR). It was found that the
      absorption spectra dramatically change when the monolayers are assembled into the
      multilayers on different substrates (quartz or Au). In the case of the
      multilayers on Au thin film (d = 200 nm), the LSPR peak is shifted to longer
      wavelength at the near-IR region by increasing the number of layers. The
      absorbance also depends on the layer number and shows the nonlinear behavior. On
      the other hand, the multilayers on quartz substrate show neither such LSPR peak
      shift nor nonlinear response of absorbance. The layer number dependence on metal
      surfaces can be interpreted as the combined effects between the near-field
      coupling of the LSPR and the far-field optics of the stratified metamaterial
      films, as proposed in our previous study. We also report the spectroscopic
      properties of hybrid multilayers composed of two kinds of monolayers, i.e., Au
      nanosheet and Ag nanosheet. The combination of the different metal nanoparticle
      sheets realizes more flexible plasmonic color tuning.

PMID- 23153009
TI  - In vitro amplification of ovine prions from scrapie-infected sheep from Great
      Britain reveals distinct patterns of propagation.
AB  - BACKGROUND: Protein misfolding cyclic amplification (PMCA) is a method that
      facilitates the detection of prions from many sources of transmissible spongiform
      encephalopathy (TSE). Sheep scrapie represents a unique diversity of prion
      disease agents in a range of susceptible PRNP genotypes. In this study PMCA was
      assessed on a range of Great Britain (GB) sheep scrapie isolates to determine the
      applicability to veterinary diagnosis of ovine TSE. RESULTS: PrPSc amplification
      by protein misfolding cyclic amplification (PMCA) was assessed as a diagnostic
      tool for field cases of scrapie. The technique was initially applied to thirty
      seven isolates of scrapie from diverse geographical locations around GB, and
      involved sheep of various breeds and PRNP genotypes. All samples were amplified
      in either VRQ and/or ARQ PrPC substrate. For PrPSc from sheep with at least one
      VRQ allele, all samples amplified efficiently in VRQ PrPC but only PrPSc from
      ARH/VRQ sheep amplified in both substrates. PrPSc from ARQ/ARQ sheep displayed
      two amplification patterns, one that amplified in both substrates and one that
      only amplified in ARQ PrPC. These amplification patterns were consistent for a
      further 14/15 flock/farm mates of these sheep. Furthermore experimental scrapie
      strains SSBP1, Dawson, CH1641 and MRI were analysed. SSBP1 and Dawson (from
      VRQ/VRQ sheep) amplified in VRQ but not ARQ substrate. MRI scrapie (from ARQ/ARQ
      sheep) nor CH1641 did not amplify in ARQ or VRQ substrate; these strains required
      an enhanced PMCA method incorporating polyadenylic acid (poly(A)) to achieve
      amplification. CONCLUSIONS: PrPsc from 52 classical scrapie GB field isolates
      amplified in VRQ or ARQ or both substrates and supports the use of PMCA as a
      rapid assay for the detection of a wide range of ovine classical scrapie
      infections involving multiple PRNP genotypes and scrapie strains.

PMID- 23153011
TI  - Asthma and atopy in children born by caesarean section: effect modification by
      family history of allergies - a population based cross-sectional study.
AB  - BACKGROUND: Studies on the association of birth by caesarean section (C/S) and
      allergies have produced conflicting findings. Furthermore, evidence on whether
      this association may differ in those at risk of atopy is limited. This study aims
      to investigate the association of mode of delivery with asthma and atopic
      sensitization and the extent to which any effect is modified by family history of
      allergies. METHODS: Asthma outcomes were assessed cross-sectionally in 2216
      children at age 8 on the basis of parents' responses to the ISAAC questionnaire
      whilst skin prick tests to eleven aeroallergens were also performed in a subgroup
      of 746 children. Adjusted odds ratios of asthma and atopy by mode of delivery
      were estimated in multivariable logistic models while evidence of effect
      modification was examined by introducing interaction terms in the models.
      RESULTS: After adjusting for potential confounders, children born by C/S appeared
      significantly more likely than those born vaginally to report ever wheezing (OR
      1.36, 95% CI 1.07-1.71), asthma diagnosis (OR 1.41, 95% CI 1.09-1.83) and be
      atopic (OR 1.67, 95% CI 1.08-2.60). There was modest evidence that family history
      of allergies may modify the effect of C/S delivery on atopy (p for effect
      modification=0.06) but this was not the case for the asthma outcomes.
      Specifically, while more than a two-fold increase in the odds of being a topic
      was observed in children with a family history of allergies if born by C/S (OR
      2.62, 95% CI 1.38-5.00), no association was observed in children without a family
      history of allergies (OR 1.16, 95% CI 0.64-2.11). CONCLUSIONS: Birth by C/S is
      associated with asthma and atopic sensitization in childhood. The association of
      C/S and atopy appears more pronounced in children with family history of
      allergies.

PMID- 23153012
TI  - Chronic hypertrophic ganglioneuritis mimicking spinal nerve neoplasia: clinical,
      imaging, pathologic findings, and outcome after surgical treatment.
AB  - OBJECTIVE: To report the clinical, imaging, pathologic findings, surgical
      planning, and long-term outcome after surgery in a dog with neurologic deficits
      because of a hypertrophic ganglioneuritis that compressed the spinal cord. STUDY
      DESIGN: Clinical report. ANIMAL: An 8-year-old male intact Yorkshire terrier.
      METHODS: The dog had ambulatory tetraparesis and neurologic examination was
      consistent with a C1-C5 myelopathy. Magnetic resonance imaging (MRI) revealed
      enlargement of the left C2 spinal nerve causing compression of the spinal cord.
      The main differential diagnosis was spinal nerve neoplasia with compression and
      possibly spinal cord invasion. On ultrasonography, there was enlargement of the
      spinal nerve and fine needle aspiration did not show evidence of neoplasia.
      Fascicular biopsy of the spinal nerve was consistent with enlargement because of
      chronic inflammation (hypertrophic neuritis). RESULTS: Hemilaminectomy followed
      by durotomy and rhizotomy allowed resection of an intradural-extramedullary mass
      that was the enlarged left C2 spinal nerve. Histopathology was consistent with a
      hypertrophic ganglioneuritis. Thirteen months later the dog remained free of
      clinical signs. CONCLUSION: Hypertrophic neuritis affecting the spinal nerves may
      be misdiagnosed as spinal nerve neoplasia that in dogs is usually malignant with
      a poor prognosis. Focal spinal nerve lesions with compression of the spinal cord
      evident on MRI may be inflammatory and are not necessarily a neoplastic
      condition.

PMID- 23153013
TI  - Clinical practice guidelines for patients with gastrointestinal stromal tumor in
      Taiwan.
AB  - For many years, the understanding of gastrointestinal stromal tumors (GISTs),
      which are the most common mesenchymal tumors of the gastrointestinal tract, has
      been very limited. However, it is now possible to provide a more precise
      definition through the use of pathology classification and molecular techniques.
      Coupled with the advancement of clinical practice, especially the development of
      targeted therapy, there is now a much better insight into its treatment. At
      present, organizations such as the National Comprehensive Cancer Network in the
      USA and the European Society for Medical Oncology in Europe have established a
      consensus and drawn up guidelines for the diagnosis, treatment, and follow-up of
      GISTs.With experts coming from various districts in Taiwan and combining the most
      recent clinical data and experiences, the Taiwan Surgical Society of
      Gastroenterology drafted the first national GIST treatment guidelines after a
      consensus meeting in 2007. Following subsequent advances in GIST diagnosis and
      treatment, further revisions and modifications have been made to the original
      guidelines. We present here the updated consensus and recommendations of the
      Taiwan Surgical Society of Gastroenterology for the diagnosis and treatment of
      GIST. We hope these guidelines can help enhance the quality of diagnosis,
      treatment, and care of patients with GIST in Taiwan.

PMID- 23153014
TI  - An organisational analysis of the implementation of telecare and telehealth: the
      whole systems demonstrator.
AB  - BACKGROUND: To investigate organisational factors influencing the implementation
      challenges of redesigning services for people with long term conditions in three
      locations in England, using remote care (telehealth and telecare). METHODS: Case
      studies of three sites forming the UK Department of Health's Whole Systems
      Demonstrator (WSD) Programme. Qualitative research techniques were used to obtain
      data from various sources, including semi-structured interviews, observation of
      meetings over the course programme and prior to its launch, and document review.
      Participants were managers and practitioners involved in the implementation of
      remote care services. RESULTS: The implementation of remote care was nested
      within a large pragmatic cluster randomised controlled trial (RCT), which formed
      a core element of the WSD programme. To produce robust benefits evidence, many
      aspect of the trial design could not be easily adapted to local circumstances.
      While remote care was successfully rolled-out, wider implementation lessons and
      levels of organisational learning across the sites were hindered by the
      requirements of the RCT. CONCLUSIONS: The implementation of a complex innovation
      such as remote care requires it to organically evolve, be responsive and
      adaptable to the local health and social care system, driven by support from
      front-line staff and management. This need for evolution was not always aligned
      with the imperative to gather robust benefits evidence. This tension needs to be
      resolved if government ambitions for the evidence-based scaling-up of remote care
      are to be realised.

PMID- 23153015
TI  - Diimine triscarbonyl Re(I) of isomeric pyridyl-fulvene ligands: an
      electrochemical, spectroscopic, and computational investigation.
AB  - The synthesis and characterization of a novel family of positively charged fac
      [Re(bpy)(CO)(3)(L)]PF(6) (bpy = 2,2'-bipyridine) complexes are reported, where L
      is a pyridine functionalized in para or meta position with a fulvene moiety,
      namely, 4-fluoren-9-ylidenemethyl-pyridine (pFpy) and 3-fluoren-9-ylidenemethyl
      pyridine (mFpy). The complexes were prepared in high yield (86%) by direct
      addition at room temperature of the corresponding pyridine to the tetrahydrofuran
      (THF) adduct fac-[Re(bpy)(CO)(3)(THF)][PF(6)] precursor. Both ligand and complex
      structures were fully characterized by a variety of techniques including X-ray
      crystallography. The complexes did not exhibit the expected triplet mixed metal
      ligand-to-ligand charge transfer (MLLCT) emission, because of its deactivation by
      the non-emissive triplet excited state of fulvene. The absorption profile shows
      that the MLLCT is overshadowed by the fulvene centered pi-pi* transition of
      higher molar absorptivity as shown by time dependent density functional theory
      (TD-DFT) calculations. The position of the fulvene on the pyridyl ring has a
      large effect on this transition, the para position displaying a much higher
      absorption coefficient (21.3 * 10(3) M(-1) cm(-1)) at lower energy (364 nm) than
      the meta position (331 nm, 16.0 * 10(3) M(-1) cm(-1)).

PMID- 23153016
TI  - Enhanced dissolution of manganese oxide in ice compared to aqueous phase under
      illuminated and dark conditions.
AB  - Manganese is one of the common elements in the Earth's crust and an essential
      micronutrient for all living things. The reductive dissolution of particulate
      manganese oxide is a dominant process to enhance mobility and bioavailability of
      manganese for the use of living organisms. In this work, we investigated the
      reductive dissolution of manganese oxides trapped in ice (at -20  degrees C)
      under dark and light irradiation (visible: lambda > 400 nm and UV: lambda > 300
      nm) in comparison with their counterparts in aqueous solution (at 25  degrees C).
      The reductive dissolution of synthetic MnO2, which took place slowly in aqueous
      solution, was significantly accelerated in ice phase both in the presence and
      absence of light: about 5 times more dissolution in ice phase than in liquid
      water after 6 h UV irradiation in the presence of formic acid. The enhanced
      dissolution in ice was observed under both UV and visible irradiation although
      the rate was much slower in the latter condition. The reductive dissolution rate
      of Mn(II)(aq) (under both irradiation and dark conditions) gradually increased
      with decreasing pH below 6 in both aqueous and ice phases, and the dissolution
      rates were consistently faster in ice under all tested conditions. The enhanced
      generation of Mn(II)(aq) in ice can be mainly explained in terms of freeze
      concentration of electron donors, protons, and MnO2 in liquid-like ice grain
      boundaries. The outdoor solar experiment conducted in Arctic region (Ny-Alesund,
      Svalbard, 78 degrees 55'N) also showed that the photoreductive dissolution of
      manganese oxide is enhanced in ice. The present results imply that the
      dissolution of natural minerals like manganese oxides can be enhanced in icy
      environments such as polar region, upper atmosphere, and frozen soil.

PMID- 23153017
TI  - Assessment of hemodynamic efficacy and safety of 6% hydroxyethyl starch 130/0.4
      vs. 0.9% NaCl fluid replacement in patients with severe sepsis: how to guide
      fluid therapy?

PMID- 23153018
TI  - In vitro biocompatibility and antimicrobial activity of poly(epsilon
      caprolactone)/montmorillonite nanocomposites.
AB  - A triblock copolymer based on poly(epsilon-caprolactone) (PCL) and 2-(N,N
      diethylamino)ethyl methacrylate (DEAEMA)/2-(methyl-7-nitrobenzofurazan)amino
      ethyl acrylate (NBD-NAcri), was synthesized via atom transfer radical
      polymerization (ATRP). The corresponding chlorohydrated copolymer, named as PCL-b
      DEAEMA, was prepared and anchored via cationic exchange on montmorillonite (MMT)
      surface. (PCL)/layered silicate nanocomposites were prepared through melt
      intercalation, and XRD and TEM analysis showed an exfoliated/intercalated
      morphology for organomodified clay. The surface characterization of the
      nanocomposites was undertaken by using contact angle and AFM. An increase in the
      contact angle was observed in the PCL/MMT(PCL-b-DEAEMA) nanocomposites with
      respect to PCL. The AFM analysis showed that the surface of the nanocomposites
      became rougher with respect to the PCL when MMTk10 or MMT(PCL-b-DEAEMA) was
      incorporated, and the value increased with the clay content. The antimicrobial
      activity of the nanocomposites against B. subtilis and P. putida was tested. It
      is remarkable that the biodegradation of PCL/MMT(PCL-b-DEAEMA) nanocomposites,
      monitored by the production of carbon dioxide and by chemiluminescence emission,
      was inhibited or retarded with respect to the PCL and PCL/1-MMTk10. It would
      indicate that nature of organomodifier in the clay play an important role in B.
      subtilis and P. putida adhesion processes. Biocompatibility studies demonstrate
      that both PCL and PCL/MMT materials allow the culture of murine L929 fibroblasts
      on its surface with high viability, very low apoptosis, and without plasma
      membrane damage, making these materials very adequate for tissue engineering.

PMID- 23153019
TI  - Cultures of risk and their influence on birth in rural British Columbia.
AB  - BACKGROUND: A significant number of Canadian rural communities offer local
      maternity services in the absence of caesarean section back-up to parturient
      residents. These communities are witnessing a high outflow of women leaving to
      give birth in larger centres to ensure immediate access to the procedure. A
      minority of women choose to stay in their home communities to give birth in the
      absence of such access. In this instance, decision-making criteria and
      conceptions of risk between physicians and parturient women may not align due to
      the privileging of different risk factors. METHODS: In-depth qualitative
      interviews and focus groups with 27 care providers and 43 women from 3 rural
      communities in B.C. RESULTS: When birth was planned locally, physicians expressed
      an awareness and acceptance of the clinical risk incurred. Likewise, when birth
      was planned outside the local community, most parturient women expressed an
      awareness and acceptance of the social risk incurred due to leaving the
      community. CONCLUSIONS: The tensions created by these contrasting approaches
      relate to underlying values and beliefs. As such, an awareness can address the
      impasse and work to provide a resolution to the competing prioritizations of
      risk.

PMID- 23153020
TI  - Cervical length and risk of antepartum hemorrhage in presence of low-lying
      placenta.
AB  - OBJECTIVES: To evaluate whether transvaginal ultrasound cervical length (TVU CL)
      can predict antepartum bleeding (APB) in women with low-lying placenta. STUDY
      DESIGN: A retrospective study was performed including pregnancies with low-lying
      placenta for which third trimester TVU CL was available. Multiple pregnancies
      were excluded. Short cervix was defined as TVU CL <=25 mm. Outcomes of interest
      were compared with respect to the TVU CL. RESULTS: Forty three cases of singleton
      pregnancies complicated by low-lying placenta in third trimester were identified.
      Short cervix was reported in 8 cases (19%). APB (75% vs. 31 %, p = 0.02), blood
      transfusions (25% vs. 3%, p = 0.02), lower birth weight (2246 vs. 2985 g, p =
      0.02), and neonatal intensive care unit (NICU) admissions (50% vs. 17%, p = 0.04)
      were more frequent in the women with short cervix. Rate of unplanned cesarean
      delivery for APB was similar between both the groups (25% vs. 28%, p = 0.83).
      CONCLUSIONS: In women with low-lying placenta persisting into third trimester,
      short cervical length can be used as a predictor for APB.

PMID- 23153021
TI  - Genetic polymorphisms in FAS (CD95) and FAS ligand (CD178) promoters and risk of
      tobacco-related oral carcinoma: gene-gene interactions in high-risk Indians.
AB  - We assessed the association of functional single nucleotide polymorphisms (SNP)
      in FAS -1377, -670 and FAS ligand (FASL) -844 promoters in 139 oral cancer
      patients and 126 normal subjects by PCR-RFLP. In logistic regression analysis FAS
      -1377 GA genotype appeared to marginally increase the risk while FASL -844 TC
      genotype appeared as low risk factor. The combined genotypes FAS -1377 GA or AA
      and FASL -844 TT (p <0.03), and FAS -670 AG or GG and FASL -844 TT (p <0.007)
      appeared to double the risk. FAS and FASL gene-gene and gene-environment
      interactions seems to modulate susceptibility/resistance to tobacco-related oral
      cancer in Indians.

PMID- 23153023
TI  - Beyond the Castro: the role of demographics in the selection of gay and lesbian
      enclaves.
AB  - Although some qualitative research has noted differences in gay and lesbian
      enclaves based on characteristics such as race and sex, in this article, we draw
      upon quantitative data from the U.S. Census to demonstrate the manner in which
      enclave formation is affected by the interaction of sexual orientation and other
      demographic characteristics (such as sex, race, age, and income). We focus our
      attention on enclaves located in three counties in the San Francisco Bay Area:
      San Francisco County, Alameda County, and Sonoma County as one example. Even
      though these spaces fall within close proximity to one another and share similar
      geographic appeal, our analyses indicate that these enclaves are far from
      homogenous in terms of the demographic composition of their inhabitants. These
      quantitative analyses provide further support to past qualitative findings, as
      well as highlight additional distinctions in the manner in which demographics
      affect enclave selection. We supplement our demographic analyses with supporting
      field research and interviews, further highlighting both the variation and the
      commonalities of these enclaves. Overall, our findings promote an expansion of
      the understanding how intersecting demographic characteristics affect selection
      of a particular enclave and what may constitute a gay enclave.

PMID- 23153022
TI  - The origin of modern frogs (Neobatrachia) was accompanied by acceleration in
      mitochondrial and nuclear substitution rates.
AB  - BACKGROUND: Understanding the causes underlying heterogeneity of molecular
      evolutionary rates among lineages is a long-standing and central question in
      evolutionary biology. Although several earlier studies showed that modern frogs
      (Neobatrachia) experienced an acceleration of mitochondrial gene substitution
      rates compared to non-neobatrachian relatives, no further characterization of
      this phenomenon was attempted. To gain new insights on this topic, we sequenced
      the complete mitochondrial genomes and nine nuclear loci of one pelobatoid
      (Pelodytes punctatus) and five neobatrachians, Heleophryne regis
      (Heleophrynidae), Lechriodus melanopyga (Limnodynastidae), Calyptocephalella gayi
      (Calyptocephalellidae), Telmatobius bolivianus (Ceratophryidae), and Sooglossus
      thomasseti (Sooglossidae). These represent major clades not included in previous
      mitogenomic analyses, and most of them are remarkably species-poor compared to
      other neobatrachians. RESULTS: We reconstructed a fully resolved and robust
      phylogeny of extant frogs based on the new mitochondrial and nuclear sequence
      data, and dated major cladogenetic events. The reconstructed tree recovered
      Heleophryne as sister group to all other neobatrachians, the Australasian
      Lechriodus and the South American Calyptocephalella formed a clade that was the
      sister group to Nobleobatrachia, and the Seychellois Sooglossus was recovered as
      the sister group of Ranoides. We used relative-rate tests and direct comparison
      of branch lengths from mitochondrial and nuclear-based trees to demonstrate that
      both mitochondrial and nuclear evolutionary rates are significantly higher in all
      neobatrachians compared to their non-neobatrachian relatives, and that such rate
      acceleration started at the origin of Neobatrachia. CONCLUSIONS: Through the
      analysis of the selection coefficient (omega) in different branches of the tree,
      we found compelling evidence of relaxation of purifying selection in
      neobatrachians, which could (at least in part) explain the observed higher
      mitochondrial and nuclear substitution rates in this clade. Our analyses allowed
      us to discard that changes in substitution rates could be correlated with
      increased mitochondrial genome rearrangement or diversification rates observed in
      different lineages of neobatrachians.

PMID- 23153024
TI  - Support for a fluid-continuum model of sexual orientation: a large-scale Internet
      study.
AB  - In a study with 17,785 subjects obtained over the Internet from the United States
      and 47 other countries, Kinsey's hypothesis that sexual orientation lies on a
      continuum was supported. Self-identifications of subjects as gay, straight,
      bisexual, and other corresponded to broad, skewed distributions, suggesting that
      such terms are misleading for many people. Sexual orientation range-roughly, how
      much flexibility someone has in expressing sexual orientation-was also measured.
      The results support a fluid-continuum model of sexual orientation, according to
      which genetic and environmental factors determine both the size of the sexual
      orientation range and the point at which an individual's sexual orientation is
      centered on the continuum.

PMID- 23153025
TI  - When Christianity and homosexuality collide: understanding the potential
      intrapersonal conflict.
AB  - Reconciling sexual orientation with religious and spiritual beliefs can be
      challenging for Christian homosexuals, since many Christian churches teach that
      homosexual behavior is sinful. A qualitative study of 10 male and 10 female
      Christian homosexuals was conducted via semistructured interviews. This article
      seeks to explore the potential conflict between Christianity and homosexuality
      faced by the respondents. Participants' life stories and experiences varied
      widely. A few respondents were unaffected by the potential conflict between
      Christianity and homosexuality, however, the majority were affected. Effects
      included depression, guilt, anxiety, suicidal ideation, and alienation.
      Implications of the findings for support personnel are included.

PMID- 23153026
TI  - Modernization of power in legal and medical discourses: the birth of the (male)
      homosexual in Hong Kong and its aftermath.
AB  - The removal of homosexuality from the list of mental disorders and the repeal of
      restrictive sexual laws deem that Foucault's argument on the discursive control
      of homosexuality requires refinement to take into consideration the continual
      modernization and improvement of power. This article examines the multilayered
      discursive terrain in Hong Kong where homosexuality is created, regulated, and
      contested in the contemporary era. With the popularization of human rights
      discourse, sexual dissidents are not simply treated as criminal or pathological;
      rather, legal and medical discourses have shifted to an increasing reliance on
      notions of risk to put mechanisms of social regulation in place.

PMID- 23153027
TI  - Portuguese adolescents' attitudes toward sexual minorities: transphobia,
      homophobia, and gender role beliefs.
AB  - Research has shown that negative attitudes toward lesbians and gay men are common
      and widespread in Western societies. However, few studies have addressed
      attitudes toward transgender individuals. In addition, although research has
      shown that homophobic harassment and bullying is highly common among adolescents,
      little is known about adolescent's attitudes toward sexual minorities. This study
      aimed to fill these gaps in knowledge, by investigating adolescents' attitudes
      toward transgender individuals and possible attitudinal correlates of those
      attitudes. Participants (N = 188; 62 males and 126 females) were recruited in
      high schools in Lisbon, Portugal. Age ranged from 15 to 19 years (M = 17; SD =
      .96). Participants completed a questionnaire booklet measuring attitudes toward
      transgender individuals, lesbians, and gay men, and gender role beliefs. Results
      revealed that attitudes toward transgender individuals were significantly
      correlated with all attitude measures. Specifically, it was revealed that those
      participants who endorsed negative attitudes toward transgender individuals were
      also endorsing of negative attitudes toward lesbians and gay men and tended to
      adhere to traditional gender roles. A significant gender effect was found with
      males being more negative toward sexual minorities than females, but these
      negative attitudes were more extreme toward gay men than toward lesbian women.
      Implications of these findings are discussed.

PMID- 23153029
TI  - The progesterone positive feedback effect in women after ovariectomy.
AB  - Various ovarian substances regulate the secretion of gonadotrophins during the
      menstrual cycle, but there are still several unclarified issues. The aim of this
      study was to investigate the positive feedback effect of progesterone during the
      immediate period following ovariectomy. Experiments were performed in 12 normally
      cycling women (aged 39-49 years). Following abdominal hysterectomy plus bilateral
      ovariectomy performed on cycle day 3 (day 0), the women received either estradiol
      via skin patches (days 0-7, n = 6, group 1) or estradiol as above plus vaginal
      progesterone (days 1-7, n = 6, group 2). Serum estradiol values increased
      similarly in the two groups. After the operation, serum progesterone levels
      decreased significantly in group 1, while in group 2 they remained stable
      becoming higher than in group 1 (p < 0.05). An LH and an FSH surge occurred in
      group 2 with the values after the peak returning to the pre-surge baseline. In
      contrast, in group 1 LH and FSH levels following an initial decrease, increased
      gradually until the end of the experiment. These results demonstrate that,
      despite a variable response to estrogens, the positive feedback effect of
      progesterone remained intact immediately after ovariectomy in women. It is
      suggested that it is the combining action of estradiol and progesterone that can
      ensure the expression of a positive feedback mechanism in women.

PMID- 23153030
TI  - Vocal fold hemorrhage in a CML patient after Glivec treatment.

PMID- 23153031
TI  - Microfabricated arrays for splitting and assay of clonal colonies.
AB  - A microfabricated platform was developed for highly parallel and efficient colony
      picking, splitting, and clone identification. A pallet array provided patterned
      cell colonies which mated to a second printing array composed of bridging
      microstructures formed by a supporting base and attached post. The posts enabled
      mammalian cells from colonies initially cultured on the pallet array to migrate
      to corresponding sites on the printing array. Separation of the arrays
      simultaneously split the colonies, creating a patterned replica. Optimization of
      array elements provided transfer efficiencies greater than 90% using bridging
      posts of 30 MUm diameter and 100 MUm length and total colony numbers of 3000.
      Studies using five mammalian cell lines demonstrated that a variety of adherent
      cell types could be cultured and effectively split with printing efficiencies of
      78-92%. To demonstrate the technique's utility, clonal cell lines with siRNA
      knockdown of Coronin 1B were generated using the arrays and compared to a
      traditional FACS/Western Blotting-based approach. Identification of target clones
      required a destructive assay to identify cells with an absence of Coronin 1B
      brought about by the successful infection of interfering shRNA construct. By
      virtue of miniaturization and its parallel format, the platform enabled the
      identification and generation of 12 target clones from a starting sample of only
      3900 cells and required only 5 man hours over 11 days. In contrast, the
      traditional method required 500,000 cells and generated only 5 target clones with
      34 man hours expended over 47 days. These data support the considerable reduction
      in time, manpower, and reagents using the miniaturized platform for clonal
      selection by destructive assay versus conventional approaches.

PMID- 23153033
TI  - EPIPOI: a user-friendly analytical tool for the extraction and visualization of
      temporal parameters from epidemiological time series.
AB  - BACKGROUND: There is an increasing need for processing and understanding relevant
      information generated by the systematic collection of public health data over
      time. However, the analysis of those time series usually requires advanced
      modeling techniques, which are not necessarily mastered by staff, technicians and
      researchers working on public health and epidemiology. Here a user-friendly tool,
      EPIPOI, is presented that facilitates the exploration and extraction of
      parameters describing trends, seasonality and anomalies that characterize
      epidemiological processes. It also enables the inspection of those parameters
      across geographic regions. Although the visual exploration and extraction of
      relevant parameters from time series data is crucial in epidemiological research,
      until now it had been largely restricted to specialists. METHODS: EPIPOI is
      freely available software developed in Matlab (The Mathworks Inc) that runs both
      on PC and Mac computers. Its friendly interface guides users intuitively through
      useful comparative analyses including the comparison of spatial patterns in
      temporal parameters. RESULTS: EPIPOI is able to handle complex analyses in an
      accessible way. A prototype has already been used to assist researchers in a
      variety of contexts from didactic use in public health workshops to the main
      analytical tool in published research. CONCLUSIONS: EPIPOI can assist public
      health officials and students to explore time series data using a broad range of
      sophisticated analytical and visualization tools. It also provides an analytical
      environment where even advanced users can benefit by enabling a higher degree of
      control over model assumptions, such as those associated with detecting disease
      outbreaks and pandemics.

PMID- 23153032
TI  - Extensive colonic necrosis following cardiac arrest and successful
      cardiopulmonary resuscitation: report of a case and literature review.
AB  - Non-occlusive colonic ischaemia is a recognized albeit rare entity related to
      low blood flow within the visceral circulation and in most reported cases the
      right colon was affected. This is the second case report in the literature of
      extensive colonic necrosis following cardiac arrest and cardiopulmonary
      resuscitation (CPR). A 83-year-old Caucasian woman was admitted to our hospital
      due to a low energy hip fracture. On her way to the radiology department she
      sustained a cardiac arrest. CPR started immediately and was successful. A few
      hours later, the patient developed increasing abdominal distension and severe
      metabolic acidocis. An abdominal multidetector computed tomography (MDCT) scan
      was suggestive of intestinal ischaemia. At laparotomy, the terminal ileum was
      ischaemic and extensive colonic necrosis was found, sparing only the proximal
      third of the transverse colon. The rectum was also spared. The terminal ileum and
      the entire colon were resected and an end ileostomy was fashioned. Although the
      patient exhibited a transient improvement during the immediate postoperative
      period, she eventually died 24h later from multiple organ failure. Histology
      showed transmural colonic necrosis with no evidence of a thromboembolic process
      or vasculitis. Therefore, this entity was attributed to a low flow state within
      the intestinal circulation secondary to the cardiac arrest.

PMID- 23153035
TI  - Why the standard B3LYP/6-31G* model chemistry should not be used in DFT
      calculations of molecular thermochemistry: understanding and correcting the
      problem.
AB  - We analyze the error compensations that are responsible for the relatively good
      performance of the popular B3LYP/6-31G* model chemistry for molecular
      thermochemistry. We present the B3LYP-gCP-D3/6-31G* scheme, which corrects for
      missing London dispersion and basis set superposition error (BSSE) in a
      physically sound manner. Benchmark results for the general main group
      thermochemistry, kinetics, and noncovalent interactions set (GMTKN30) are
      presented. A detailed look is cast on organic reactions of several arenes with
      C(60), Diels-Alder reactions, and barriers to [4 + 3] cycloadditions. We
      demonstrate the practical advantages of the new B3LYP-gCP-D3/6-31G* scheme and
      show its higher robustness over standard B3LYP/6-31G*. B3LYP-gCP-D3/6-31G* is
      meant to fully substitute standard B3LYP/6-31G* calculations in the same black
      box sense at essentially no increase in computational cost. The energy
      corrections are made available by a Web service ( http://www.thch.uni
      bonn.de/tc/gcpd3 ) and by freely available software.

PMID- 23153034
TI  - Generation of the volatile spiroketals conophthorin and chalcogran by fungal
      spores on polyunsaturated fatty acids common to almonds and pistachios.
AB  - The spiroketal (E)-conophthorin has recently been reported as a semiochemical of
      the navel orangeworm moth, a major insect pest of California pistachios and
      almonds. Conophthorin and the isomeric spiroketal chalcogran are most commonly
      known as semiochemicals of several scolytid beetles. Conophthorin is both an
      insect- and plant-produced semiochemical widely recognized as a nonhost plant
      volatile from the bark of several angiosperm species. Chalcogran is the principal
      aggregation pheromone component of the six-spined spruce bark beetle. Recent
      research has shown conophthorin is produced by almonds undergoing hull-split, and
      both spiroketals are produced by mechanically damaged almonds. To better
      understand the origin of these spiroketals, the volatile emissions of orchard
      fungal spores on fatty acids common to both pistachios and almonds were
      evaluated. The volatile emission for the first 13 days of spores placed on a
      fatty acid was monitored. The spores investigated were Aspergillus flavus
      (atoxigenic), A. flavus (toxigenic), Aspergillus niger, Aspergillus parasiticus,
      Penicillium glabrum, and Rhizopus stolonifer. The fatty acids used as growth
      media were palmitic, oleic, linoleic, and linolenic. Spores on linoleic acid
      produced both spiroketals, those on linolenic acid produced only chalcogran, and
      those on palmitic and oleic acid did not produce either spiroketal. This is the
      first report of the spiroketals conophthorin and chalcogran from a fungal source.

PMID- 23153036
TI  - Black pepper essential oil to enhance intravenous catheter insertion in patients
      with poor vein visibility: a controlled study.
AB  - OBJECTIVES: To evaluate the effect of topically applied black pepper essential
      oil on easing intravenous catheter insertion (IVC) in patients with no palpable
      or visible veins compared to a control group (standard nursing practice). DESIGN:
      Randomized, controlled study. SUBJECTS: One hundred twenty hospitalized patients,
      who were referred to a hospital vascular team because of difficulty in accessing
      veins for IVC insertion. INTERVENTIONS: Topical application of 20% essential oil
      of black pepper in aloe vera gel or standard nursing care (hot packs with or
      without vigorous tactile stimulation). OUTCOME MEASURES: Pre- and post-test vein
      visibility and/or palpability and number of attempts at IVC insertion. RESULTS: A
      higher percentage of patients achieved optimal scoring (vein score=2) or improved
      scoring (vein score of 1 or 2) to black pepper intervention than standard nursing
      care. The black pepper group also reduced the number of patients whose veins were
      still not visible or palpable after the intervention to nearly half that of the
      control group (p<0.05). The number of IVC attempts following black pepper was
      also half that of the control group. CONCLUSION: Topical application of black
      pepper is a viable and effective way to enhance vein visibility and palpability
      prior to intravenous insertion in patients with limited vein accessibility; it
      also improves ease of IVC insertion.

PMID- 23153037
TI  - Alteration of the tongue manifestation reflects clinical outcomes of peptic ulcer
      disease.
AB  - OBJECTIVES: This study investigated whether the tongue inspection technique in
      Traditional Chinese Medicine (TCM) can be used as a noninvasive auxiliary
      diagnostic tool to differentiate the subtypes of peptic ulcer disease (PUD) and
      as an indicator of therapeutic efficacy. SUBJECTS AND METHODS: A total of 198
      outpatients from the China Medical University Hospital were recruited. The
      control group comprised 50 healthy adults. The remaining 148 patients were
      diagnosed with gastric ulcer, duodenal ulcer, or Helicobacter pylori (Hp)
      infection using upper gastrointestinal (GI) endoscopy, biopsy, and Campylobacter
      like organism test. Tongue appearance was evaluated by a physician experienced in
      clinical Chinese medicine. Images of the tongue were immediately recorded using a
      high-resolution digital camera system. RESULTS: The affected group of 148
      patients received an 8-week course of ulcer therapy. Of these, 108 patients
      infected with Hp were subjected to triple therapy in the first week. Forty-nine
      of these 108 cases infected with Hp completed secondary examination of upper GI
      endoscopy and tongue inspection. Forty-one of 49 cases (83.7%) were fully cured
      of Hp infection. These results showed that the color of the tongue body did not
      change in the cured patients; however, tongue fur was markedly thinner with a
      color change to white (p<0.05), while sublingual veins with engorgement (p<0.05)
      and blood stasis (p<0.01) improved after the ulcer healed and Hp was eradicated.
      CONCLUSIONS: TCM tongue inspection can be potentially used as a noninvasive
      auxiliary diagnostic method and as an indicator for clinical outcomes for
      patients with PUD.

PMID- 23153038
TI  - Electrospun fibrous mats on lithographically micropatterned collectors to control
      cellular behaviors.
AB  - Spatial arrangement of multiple cell types plays a critical role in maintaining
      the viability of cells and functionality of tissues. Micropatterning has been
      used to fabricate scaffolds to modulate cell distribution, growth, and functions
      for reconstructing the anisotropy in native tissues. In the current study, a
      glass substrate patterned with an electrically conductive circuit was prepared by
      lithography as a collector for electrospinning. Densely packed fibers were
      deposited on the top of silver strips and patterned fibrous mats were obtained
      with distinct ridge and groove areas. Orthogonal alignment was shown for fibers
      in the ridge and groove areas, and the pattern feature and fiber alignment were
      well maintained in the ridge during incubation of cells with patterned fibrous
      mats. Sequential confocal laser scanning from the top of cell-loaded fibrous mats
      indicated that a larger number of cells were spread in the ridge than that in the
      groove areas, and cells penetrated into the fibrous mats in the ridge.
      Microscopic observation and immunofluorescent staining indicated that cells and
      collagen deposition appeared to have distinct patterns on the fibrous scaffold
      and aligned along the directionality of fibers with an elongated morphology. It
      is concluded that lithography can provide the design flexibility of collectors
      with micrometer-scale precision patterning, and cells can be confined to precise
      locations, sizes, and shapes by the use of micropatterned fibrous scaffolds
      without any adverse effect on the cell viability and function. The results
      suggest the potential of patterned electrospun fibrous mats to construct complex
      tissues of well organized multiple cell types and with spatially distributed
      extracellular matrices.

PMID- 23153039
TI  - Role of TLR4/NADPH oxidase/ROS-activated p38 MAPK in VCAM-1 expression induced by
      lipopolysaccharide in human renal mesangial cells.
AB  - BACKGROUND: In bacteria-induced glomerulonephritis, Toll-like receptor 4 (TLR4)
      activation by lipopolysaccharide (LPS, a key component of the outer membranes of
      Gram-negative bacteria) can increase oxidative stress and the expression of
      vascular cell adhesion molecule-1 (VCAM-1), which recruits leukocytes to the
      glomerular mesangium. However, the mechanisms underlying VCAM-1 expression
      induced by LPS are still unclear in human renal mesangial cells (HRMCs). RESULTS:
      We demonstrated that LPS induced VCAM-1 mRNA and protein levels associated with
      an increase in the promoter activity of VCAM-1, determined by Western blot, RT
      PCR, and promoter assay. LPS-induced responses were inhibited by transfection
      with siRNAs of TLR4, myeloid differentiation factor 88 (MyD88), Nox2, Nox4,
      p47phox, c-Src, p38 MAPK, activating transcription factor 2 (ATF2), and p300 or
      pretreatment with the inhibitors of reactive oxygen species (ROS, edaravone),
      NADPH oxidase [apocynin (APO) or diphenyleneiodonium chloride (DPI)], c-Src
      (PP1), p38 MAPK (SB202190), and p300 (GR343). LPS induced NADPH oxidase
      activation, ROS production, and p47phox translocation from the cytosol to the
      membrane, which were reduced by PP1 or c-Src siRNA. We observed that LPS induced
      TLR4, MyD88, c-Src, and p47phox complex formation determined by co
      immunoprecipitation and Western blot. We further demonstrated that LPS stimulated
      ATF2 and p300 phosphorylation and complex formation via a c-Src/NADPH
      oxidase/ROS/p38 MAPK pathway. Up-regulation of VCAM-1 led to enhancing monocyte
      adhesion to HRMCs challenged with LPS, which was inhibited by siRNAs of c-Src,
      p47phox, p38 MAPK, ATF2, and p300 or pretreatment with an anti-VCAM-1
      neutralizing antibody. CONCLUSIONS: In HRMCs, LPS-induced VCAM-1 expression was,
      at least in part, mediated through a TLR4/MyD88/ c-Src/NADPH oxidase/ROS/p38 MAPK
      dependent p300 and ATF2 pathway associated with recruitment of monocyte adhesion
      to kidney. Blockade of these pathways may reduce monocyte adhesion via VCAM-1
      suppression and attenuation of the inflammatory responses in renal diseases.

PMID- 23153040
TI  - Strategies for coupling molecular units if subsequent decoupling is required.

PMID- 23153041
TI  - Microbiome dynamics of human epidermis following skin barrier disruption.
AB  - BACKGROUND: Recent advances in sequencing technologies have enabled metagenomic
      analyses of many human body sites. Several studies have catalogued the
      composition of bacterial communities of the surface of human skin, mostly under
      static conditions in healthy volunteers. Skin injury will disturb the cutaneous
      homeostasis of the host tissue and its commensal microbiota, but the dynamics of
      this process have not been studied before. Here we analyzed the microbiota of the
      surface layer and the deeper layers of the stratum corneum of normal skin, and we
      investigated the dynamics of recolonization of skin microbiota following skin
      barrier disruption by tape stripping as a model of superficial injury. RESULTS:
      We observed gender differences in microbiota composition and showed that bacteria
      are not uniformly distributed in the stratum corneum. Phylogenetic distance
      analysis was employed to follow microbiota development during recolonization of
      injured skin. Surprisingly, the developing neo-microbiome at day 14 was more
      similar to that of the deeper stratum corneum layers than to the initial surface
      microbiome. In addition, we also observed variation in the host response towards
      superficial injury as assessed by the induction of antimicrobial protein
      expression in epidermal keratinocytes. CONCLUSIONS: We suggest that the
      microbiome of the deeper layers, rather than that of the superficial skin layer,
      may be regarded as the host indigenous microbiome. Characterization of the skin
      microbiome under dynamic conditions, and the ensuing response of the microbial
      community and host tissue, will shed further light on the complex interaction
      between resident bacteria and epidermis.

PMID- 23153043
TI  - Holy smoke: tobacco use among native american tribes in North America.
AB  - The use of tobacco by Native Americans in North America seems to have ancient
      origins and significant spiritual meaning. This article reviews archeological and
      anthropological data about the use of tobacco and its sacred significance.

PMID- 23153042
TI  - Cobalt alkyl complexes of a new family of chiral 1,3-bis(2
      pyridylimino)isoindolates and their application in asymmetric hydrosilylation.
AB  - The synthesis of a new family of chiral tridentate monoanionic NNN-pincer ligands
      based on the 1,3-bis(2-pyridylimino)isoindoline (BPI) framework is reported.
      Ligands with substituents of varying steric demand were prepared starting from
      achiral and low priced materials. A kinetic enzymatic resolution was used as a
      key step for the preparation of enantiomerically pure ligands. In this way, both
      enantiomers of a given ligand could be produced enantioselectively (>99.5% ee).
      The corresponding cobalt alkyl complexes were obtained using a pyridine alkyl
      cobalt precursor complex and were applied in asymmetric hydrosilylation of
      several prochiral alkylaryl ketones with high yields (up to 100%) and
      enantioselectivity (up to 91% ee) to give the chiral alcohols after hydrolysis.

PMID- 23153044
TI  - A prospective study of the effects of the DRD2/ANKK1 TaqIA polymorphism and
      impulsivity on smoking initiation.
AB  - This study tested whether DRD2/ANKK1 TaqIA genotype predicted smoking initiation
      and subsequent use, and effects were mediated by sensation seeking and negative
      urgency. Between 2009 and 2012, college never smokers (n = 387) completed six
      assessments over 15 months; those who reported smoking were classified as
      initiators. Logistic regression indicated that the A1 allele was associated with
      initiation (p = .003). This effect was partially mediated by sensation seeking
      and negative urgency. Effects were stronger in Asian Americans. Findings have
      implications for improving prevention by including elements focused on urges to
      seek positive or negative reinforcement. Limitations and future directions are
      discussed.

PMID- 23153045
TI  - Effects of a cross-linked hyaluronic acid based gel on the healing of open wounds
      in dogs.
AB  - OBJECTIVE: To compare effects of a cross-linked hyaluronic acid (HA) based gel
      (CMHA-S) to a standard wound management protocol on the healing of acute, full
      thickness wounds in dogs. STUDY DESIGN: A prospective, controlled, experimental
      study. ANIMALS: Purpose-bred, adult, female beagles (n = 10). METHODS: Two 2 * 2
      cm wounds were surgically created bilaterally on the trunk of each dog and each
      side randomized to treatment (CMHA-S) or control (CON) groups. Total and open
      wound areas were measured with digital image planimetry at 15 time points. From
      these data, percent contraction and percent epithelialization were calculated.
      Tissue biopsies were obtained at 6 time points and histologic features were
      scored. RESULTS: Total wound area was significantly larger and percent
      contraction was significantly less in CMHA-S compared to CON wounds at all data
      points between days 9 and 18. At day 25, and for the remainder of the study, CMHA
      S wounds were smaller and contracted more than CON wounds, reaching significance
      at day 32. Percent epithelialization was significantly less in CMHA-S compared to
      CON wounds at all data points after day 11. Histologically, fibroblastic cellular
      infiltration was significantly higher in CMHA-S wounds at day 21. CONCLUSIONS:
      CMHA-S wounds healed more slowly than CON wounds. This HA-based gel is not
      indicated in acute, full-thickness skin wounds in dogs as administered in this
      study. However, treatment may be beneficial in the mid-to-late repair stage of
      healing, or if scar minimization is desired. Further studies to evaluate the
      effects of the CMHA-S gel on canine wounds are indicated.

PMID- 23153046
TI  - Methanospirillum respiratory mRNA biomarkers correlate with hydrogenotrophic
      methanogenesis rate during growth and competition for hydrogen in an
      organochlorine-respiring mixed culture.
AB  - Molecular biomarkers hold promise for inferring rates of key metabolic activities
      in complex microbial systems. However, few studies have assessed biomarker levels
      for simultaneously occurring (and potentially competing) respirations. In this
      study, methanogenesis biomarkers for Methanospirillum hungatei were developed,
      tested, and compared to Dehalococcoides mccartyi biomarkers in a well
      characterized mixed culture. Proteomic analyses of mixed culture samples (n = 4)
      confirmed expression of many M. hungatei methanogenesis enzymes. The mRNAs for
      two oxidoreductases detected were explored as quantitative biomarkers of
      hydrogenotrophic methanogenesis: a coenzyme F(420)-reducing hydrogenase (FrcA)
      and an iron sulfur protein (MvrD). As shown previously in D. mccartyi, M.
      hungatei transcript levels correlated linearly with measured (R = 0.97 for FrcA,
      R = 0.91 for MvrD; n = 7) or calculated respiration rate (R = 0.81 for FrcA, R =
      0.62 for MvrD; n = 35) across two orders of magnitude on a log-log scale. The
      average abundance of MvrD transcripts was consistently two orders of magnitude
      lower than FrcA, regardless of experimental condition. In experiments where M.
      hungatei was competing for hydrogen with D. mccartyi, transcripts for the key
      respiratory hydrogenase HupL were generally less abundant per mL than FrcA and
      more abundant than MvrD. With no chlorinated electron acceptor added, HupL
      transcripts fell below both targets. These biomarkers hold promise for the
      prediction of in situ rates of respiration for these microbes, even when growing
      in mixed culture and utilizing a shared substrate which has important
      implications for both engineered and environmental systems. However, the
      differences in overall biomarker abundances suggest that the strength of any
      particular mRNA biomarker relies upon empirically established quantitative trends
      under a range of pertinent conditions.

PMID- 23153047
TI  - Nail apparatus melanoma: is trauma a coincidence? Is this peculiar tumor a real
      acral melanoma?
AB  - Nail Apparatus Melanoma (NAM) is rare, particularly in Caucasians. Understanding
      its pathogenesis and collecting epidemiologic data may be difficult due to its
      location and the exiguity of the case series of this cancer. Cutaneous melanoma
      has been thought related to UV radiation, and NAM is considered an acral variant
      of melanoma, even if the nail presents a specific anatomy. Little is reported
      about pathogenesis, except reports suggesting traumatic injuries as a causal
      factor. UV exposure is debated in nail melanoma because of its structure. The
      nail is, in fact, a unique structure with sun-exposed and non exposed
      melanocytes. NAM arises from the nail melanocytes, located in the nail matrix,
      which is the germinative part of the nail and composed of a proximal and distal
      portion. The proximal nail matrix lays under the proximal nail fold that covers
      it and is non-sun exposed, while the distant nail matrix, clinically visible as
      the lunula, is sun-exposed, though lying underneath the nail plate. According to
      these anatomical data, NAM is a distinct melanoma type, and studies need to
      classify it as acral melanoma or as a particular type of melanoma with its own
      pathogenesis and prognostic criteria. This study investigates potential risk
      factors of NAM, emphasizing (i) trauma and (ii) UV exposure among our NAM
      patients.

PMID- 23153048
TI  - Allergic contact dermatitis associated with Biosyn suture in a patient with
      gastroesophageal junction cancer.
AB  - A PUBMED literature review revealed no reports of allergic contact dermatitis to
      Biosyn(TM) suture material. We present the first case of such an allergic
      reaction. The case emphasizes the need to remember that suture material can
      occasionally elicit an allergic dermatitis which may increase the complications
      and morbidity associated with any surgical procedure.

PMID- 23153049
TI  - Comparing the effects of three different intravitreal injection techniques on
      vitreous reflux and intraocular pressure.
AB  - PURPOSE: To compare the effects of straight, oblique, and double-plane tunnel
      scleral intravitreal injection techniques, on short-term intraocular pressure
      (IOP) changes, occurrence of vitreous reflux (VR), and/or other complications.
      METHODS: A total of 105 patients were included in this prospective study.
      Patients were assigned randomly to one of the straight injection group (SI;
      n=35), oblique injection group (OI; n=35), or double-plane tunnel injection group
      (DPTI; n=35). The occurrence of VR and preinjection and postinjection IOP at 2
      and 6 h were compared between groups, and complications were assessed. RESULTS:
      The mean patient age was 71.1+/-6.6 years (range 58 to 86 years; 50 women and 55
      men). In the SI, OI, and DPTI groups, VR occurred in 18 (51.4%), 12 (34.3%), and
      6 patients (17.1%), respectively. Mean preinjection IOPs were 15.4, 14.8, and
      15.6 mmHg, and changed to 17.3, 18.0, and 20.0 mmHg at the second hour, and 15.7,
      16.2, and 16.1 mmHg at the sixth hour, respectively. No significant differences
      among the groups were found in terms of complications such as transient mild
      uveitis or subconjunctival hemorrhage. CONCLUSION: Double-plane tunnel injection
      prevents VR from the injection site and has no additional complications than
      other techniques.

PMID- 23153050
TI  - 2009 pandemic H1N1 influenza virus elicits similar clinical course but
      differential host transcriptional response in mouse, macaque, and swine infection
      models.
AB  - BACKGROUND: The 2009 pandemic H1N1 influenza virus emerged in swine and quickly
      became a major global health threat. In mouse, non human primate, and swine
      infection models, the pH1N1 virus efficiently replicates in the lung and induces
      pro-inflammatory host responses; however, whether similar or different cellular
      pathways were impacted by pH1N1 virus across independent infection models remains
      to be further defined. To address this we have performed a comparative
      transcriptomic analysis of acute phase responses to a single pH1N1 influenza
      virus, A/California/04/2009 (CA04), in the lung of mice, macaques and swine.
      RESULTS: Despite similarities in the clinical course, we observed differences in
      inflammatory molecules elicited, and the kinetics of their gene expression
      changes across all three species. We found genes associated with the retinoid X
      receptor (RXR) signaling pathway known to control pro-inflammatory and metabolic
      processes that were differentially regulated during infection in each species,
      though the heterodimeric RXR partner, pathway associated signaling molecules, and
      gene expression patterns varied among the three species. CONCLUSIONS: By
      comparing transcriptional changes in the context of clinical and virological
      measures, we identified differences in the host transcriptional response to pH1N1
      virus across independent models of acute infection. Antiviral resistance and the
      emergence of new influenza viruses have placed more focus on developing drugs
      that target the immune system. Underlying overt clinical disease are molecular
      events that suggest therapeutic targets identified in one host may not be
      appropriate in another.

PMID- 23153051
TI  - A retrospective evaluation of coral snake envenomation in dogs and cats: 20 cases
      (1996-2011).
AB  - OBJECTIVE: To describe the clinical signs, treatment, and outcomes of dogs and
      cats following envenomation by the eastern coral snake and to report our clinical
      experience with the use of Coralmyn. DESIGN: Retrospective study (1996-2011).
      SETTING: University teaching hospital. ANIMALS: Sixteen dogs and 4 cats with
      eastern coral snake envenomation. MEASUREMENTS AND MAIN RESULTS: Medical records
      meeting the study inclusion criteria were reviewed and evaluated for signalment,
      date and time of the snake encounter, elapsed time between encounter and hospital
      examination, initial physical examination findings, antivenom type, length of
      hospitalization, and outcome. Initial physical examination findings included:
      quiet mentation, tetraparesis, ptyalism, tachypnea, abdominal breathing, shallow
      breathing, decreased to absent gag reflex, ataxia, muscle fasciculations, and
      decreased spinal reflexes. Laboratory findings in dogs included proteinuria,
      bilirubinuria, hemeproteinuria, increased aspartate aminotransferase activity,
      increased alanine aminotransferase activity, and hemolysis. Four dogs and 2 cats
      received Coralmyn and 4 dogs received North American Coral Snake Antivenom.
      Adverse reaction to antivenom was suspected in 1 dog that received North American
      Coral Snake Antivenom. Eight of 11 envenomated dogs survived with a median length
      of hospitalization of 4.5 days. Two of 3 envenomated cats survived with a median
      length of hospitalization of 4 days. Two dogs were euthanized, 1 dog suffered
      acute respiratory arrest, and 1 cat developed tachycardia that progressed to
      pulseless electrical activity. Five dogs and 1 cat in the encounter group
      survived to discharge. CONCLUSIONS: Diagnosis of eastern coral snake envenomation
      is likely in the dog that has concomitant lower motor neuron neuropathy, bulbar
      palsy, and hemolysis. Early diagnosis is crucial as antivenom administration can
      reduce morbidity. Prognosis is considered good with 71% of the envenomated
      patients in this study surviving to discharge. Supportive care that may include
      ventilator assistance and antivenom administration are the mainstays of therapy.

PMID- 23153052
TI  - "More bang for the buck": exploring optimal approaches for guideline
      implementation through interviews with international developers.
AB  - BACKGROUND: Population based studies show that guidelines are underused. Surveys
      of international guideline developers found that many do not implement their
      guidelines. The purpose of this research was to interview guideline developers
      about implementation approaches and resources. METHODS: Semi-structured telephone
      interviews were conducted with representatives of guideline development agencies
      identified in the National Guideline Clearinghouse and sampled by country, type
      of developer, and guideline clinical indication. Participants were asked to
      comment on the benefits and resource implications of three approaches for
      guideline implementation that varied by responsibility: developers,
      intermediaries, or users. RESULTS: Thirty individuals from seven countries were
      interviewed, representing government (n = 12) and professional (n = 18)
      organizations that produced guidelines for a variety of clinical indications.
      Organizations with an implementation mandate featured widely inconsistent funding
      and staffing models, variable approaches for choosing promotional strategies, and
      an array of dissemination activities. When asked to choose a preferred approach,
      most participants selected the option of including information within guidelines
      that would help users to implement them. Given variable mandate and resources for
      implementation, it was considered the most feasible approach, and therefore most
      likely to have impact due to potentially broad use. CONCLUSIONS: While
      implementation approaches and strategies need not be standardized across
      organizations, the findings may be used by health care policy makers and
      managers, and guideline developers to generate strategic and operational plans
      that optimize implementation capacity. Further research is needed to examine how
      to optimize implementation capacity by guideline developers, intermediaries and
      users.

PMID- 23153053
TI  - Gonadotropin releasing hormone agonist and levonorgestrel-intrauterine device
      followed by in vitro fertilization program as management strategy for an
      infertile endometrial cancer patient: a case report.
AB  - BACKGROUND: A progressive delay in the age of first conception results in an
      increased frequency of endometrial cancer patients in reproductive age and
      desiring childbearing. CASE: A 38-year-old infertile woman with stage I
      endometrioid adenocarcinoma was treated with gonadotropin releasing hormone
      agonist (GnRHa) and levonorgestrel-releasing intrauterine device (LNG-IUD). After
      disease remission, she underwent a controlled ovarian stimulation for standard in
      vitro fertilization (IVF) program and had a pregnancy delivering a healthy male
      baby. Total laparoscopic hysterectomy with bilateral salpingo-oophorectomy was
      performed four months after delivery. The patient is free of disease after 3-year
      follow-up. CONCLUSION: GnRHa plus LNG-IUD followed by IVF program is a safe and
      effective fertility-sparing strategy to manage infertile patients with stage I
      endometrial cancer.

PMID- 23153054
TI  - A new approach to predicting human hepatic clearance of CYP3A4 substrates using
      monkey pharmacokinetic data.
AB  - Focusing on the genetic similarity of CYP3A subfamily enzymes (CYP3A4 and CYP3A5)
      between monkeys and humans, we have attempted to provide a single-species
      approach to predicting human hepatic clearance (CLh) of CYP3A4 substrates using
      pharmacokinetic parameters in cynomolgus monkeys following intravenous
      administrations. 2. Hepatic intrinsic clearance (CLint,h) of six CYP3A4
      substrates (alprazolam, clonazepam, diltiazem, midazolam, nifedipine, and
      quinidine), covering a wide range of clearance, in monkeys correlated well with
      that cited in literature for humans (R = 0.90) with a simple equation of Y =
      0.165X (Y: human CLint,h, X: monkey CLint,h, represented in mL/min/kg). 3. To
      verify the predictability of human CLint,h, monkey CLint,h of a test set of
      CYP3A4 substrates cited in literature (dexamethasone, nifedipine, midazolam,
      quinidine, tacrolimus, and verapamil) was applied to the equation and human
      CLint,h was calculated. The human CLint,h of all the substrates was predicted
      within 3-fold error (fold error: 0.35-2.77). 4. The predictability of human CLh
      by our method was superior to common in vivo prediction methods (allometry and
      liver blood flow method). These results suggest that human hepatic clearance of
      CYP3A4 substrates can be predicted by applying cynomolgus monkey CLint,h obtained
      following intravenous administrations in each laboratory to the simple equation.

PMID- 23153055
TI  - Isolation and identification of phase I metabolites of resibufogenin in rats.
AB  - 1. Resibufogenin (1), a major bufadienolide of Chinese medicine Chan Su, had a
      wide range of pharmacological activities. In present work, the metabolism of 1 in
      male Sprague-Dawley rats was investigated by identifying the metabolites of
      resibufogenin excreted in rat bile. 2. Following an oral dose of 60 mg/kg
      resibufagenin, nine metabolites were isolated from bile of rats, and their
      structures were identified as 3-keto- resibufogenin (2), 3-epi-resibufogenin (3),
      5beta-hydroxy-3-epi-resibufogenin (4), 1alpha, 5beta-dihydroxy-3-epi
      resibufogenin (5), 3alpha, 5beta, 14alpha, 15beta-tetrahydroxyl-bufa- 20, 22
      dienolide (6), 3alpha, 14alpha, 15beta-trihydroxy-bufa-20, 22-dienolide (7), 3
      epi- 5beta-hydroxy-bufalin (8), 12alpha, 16beta-dihydroxy-3-epi-resibufogenin
      (9), and 5beta, 16beta-dihydroxy-3-epi-resibufogenin (10), respectively, on the
      basis of widely spectroscopic methods including 2D-NMR technology. It is first
      time to describe the metabolites of 1 in vivo, and metabolites 5-7 and 9-10 are
      novel. 3. On the basis of these identified metabolites, a possible metabolism
      pathway for 1 in rats has been proposed. This is the first systematic study on
      the phase I metabolites of resibufogenin.

PMID- 23153056
TI  - The fungus Cunninghamella elegans can produce human and equine metabolites of
      selective androgen receptor modulators (SARMs).
AB  - 1. Selective androgen receptor modulators (SARMs) are a group of substances that
      have potential to be used as doping agents in sports. Being a relatively new
      group not available on the open market means that no reference materials are
      commercially available for the main metabolites. In the presented study, the in
      vitro metabolism of SARMs by the fungus Cunninghamella elegans has been
      investigated with the purpose of finding out if it can produce relevant human and
      equine metabolites. 2. Three different SARMs, S1, S4 and S24, were incubated for
      5 days with C. elegans. The samples were analysed both with and without sample
      pretreatment using ultra performance liquid chromatography coupled to high
      resolution mass spectrometry. 3. All the important phase I and some phase II
      metabolites from human and horse were formed by the fungus. They were formed
      through reactions such as hydroxylation, deacetylation, O-dephenylation, nitro
      reduction, acetylation and sulfonation. 4. The study showed that the fungus
      produced relevant metabolites of the SARMs and thus can be used to mimic
      mammalian metabolism. Furthermore, it has the potential to be used for future
      production of reference material.

PMID- 23153057
TI  - Assessment of cytochrome P450 (1A2, 2B6, 2C9 and 3A4) induction in cryopreserved
      human hepatocytes cultured in 48-well plates using the cocktail strategy.
AB  - 1. A fast, straightforward and cost-effective assay was validated for the
      assessment of CYP induction in cryopreserved human hepatocytes cultured in 48
      well plates. The cocktail strategy (in situ incubation) was used to assess the
      induction of CYP1A2, CYP2B6, CYP2C9 and CYP3A4 by using the recommended probe
      substrate, i.e. phenacetin, bupropion, diclofenac and midazolam, respectively. 2.
      Cryopreserved human hepatocytes were treated for 72 h with prototypical reference
      inducers, beta-naphthoflavone (25 uM), phenobarbital (500 uM) and rifampicin (10
      uM) as positive controls for CYP induction. The use of a cocktail strategy has
      been validated and compared to the classical approach (single incubation). The
      need of using phase II inhibitor (salicylamide) in CYP induction assay was also
      investigated. 3. By using three different batches of cryopreserved human
      hepatocytes and our conditions of incubations, we showed that there was no
      relevant drug-drug interaction using the cocktail strategy. The same conclusions
      were observed when a broad range of enzyme activity has to be assessed (wide
      range of reference inducers, i.e. EC50-Emax experiment). In addition, the
      interassay reproducibility assessment showed that the day-to-day variability was
      minimal. 4. In summary, the study showed that the conditions used (probe
      substrates, concentration of probe substrate and time of incubation) for the
      cocktail approach were appropriate for investigations of CYP induction potential
      of new chemical entities. In addition, it was also clear that the use of
      salicylamide in the incubation media was not mandatory and could generate drug
      drug interactions. For this reason, we recommend to not use salicylamide in CYP
      induction assay.

PMID- 23153058
TI  - In vitro models of xenobiotic metabolism in trout for use in environmental
      bioaccumulation studies.
AB  - 1. In vitro screens are sought as informative, alternatives to the use of animals
      in vivo and to improve upon the current use of fish liver 9000 g supernatants
      (S9) in environmental risk assessment. 2. The rates of ethoxyresorufin-O
      deethylation (relative to S9 protein) measured under different conditions of
      culture of rainbow trout hepatocytes were significantly higher than those
      detected in S9, in the order of freshly isolated hepatocytes > 10-day spheroid
      cultures > primary hepatocytes in culture > S9. The percentage of conjugated
      metabolites was also similar between freshly isolated and spheroid cultured
      hepatocytes (9.9 and 13.5%). 3. The rate of oxidation was enhanced (1.7 fold)
      when S9 was supplemented with cofactors for phase II conjugation but this was
      only approximately one tenth of the rate in freshly isolated hepatocytes (7.1
      pmol/min/mg S9 protein equivalent). 4. Hepatocytes also hydroxylated ibuprofen,
      producing two metabolites, in contrast to only one (identified as the 1-hydroxy
      derivative) using hepatic S9 fractions. 5. Since the bioaccumulation potential of
      chemicals is often based on un-supplemented S9 in incubations >= 1 h when
      activity declines, it is recommended that predictability would be greatly
      improved through the use of hepatocyte spheroids, due to their maintenance of
      activity and longevity.

PMID- 23153059
TI  - Laryngeal preservation in advanced piriform sinus squamous cell carcinomas using
      superselective intra-arterial chemoradiation therapy with three agents.
AB  - CONCLUSION: Superselective intra-arterial chemotherapy, which enables local
      control and laryngeal preservation, is a safe and useful therapy for preservation
      of nutrition, speech, and swallowing functions. OBJECTIVE: To improve the
      laryngeal preservation rate in patients with hypopharyngeal piriform sinus
      squamous cell carcinoma by superselective intra-arterial chemotherapy. METHODS:
      Fifty-seven patients received anterograde intra-arterial administration of
      docetaxel and cisplatin, and two courses of intravenous continuous infusion of 5
      fluorouracil as a neoadjuvant chemotherapy over 120 h starting on day 2.
      Concurrent chemoradiotherapy was administered from the third course to control
      the primary cancer. Remaining neck lymph node metastases were treated in
      principle by neck dissection. RESULTS: The 5- and 10-year survival rates were
      68.5% and 58.9%, respectively. The 5-year rates by the T classification were
      96.0% (10-year rate, 88.6%) in T3, 48.1% in T4a, and 16.7% in T4b. The 5- and 10
      year laryngeal preservation rates were 65.2% and 62.4%, respectively. The 5-year
      rates by the T classification were 92.4% (10-year rate, 87.6%) in T3, 36.2% in
      T4a, and 16.7% in T4b. No irreversible side effects, complications, or sequelae
      were reported. Superselective intra-arterial chemotherapy showed superior
      laryngeal preservation as well as high survival rates, particularly in T3, and
      was considered a useful therapy.

PMID- 23153061
TI  - Accurate and highly reproducible picoliter injection system for capillary
      electrophoresis.
AB  - A novel, highly accurate sample injection system for capillary electrophoresis
      (CE) was developed based on an inkjet microchip capable of reproducing exact
      introduction volumes at the picoliter level. The difficulty in analyte
      discrimination using electrokinetic injection was also overcome using this
      injection method. The injection system consisted of an XY stage, an inkjet
      droplet ejection microchip, and a reservoir with a plug-in septum. To evaluate
      the precision of the system, a mixture of NBD-labeled amino acids consisting of
      Gly, L-Phe, L-Asp, and L-Ser was separated, and the performance was compared with
      that of traditional hydrodynamic and electrokinetic injection methods. The
      results demonstrated that the introduced volume highly relied on the number of
      droplets with low relative standard derivation (RSD) and good linear correction
      coefficient in the proposed injection method. In addition, a urine sample was
      analyzed via CE coupled with the inkjet injection system for the detection of the
      amino acid taurine. The concentration of urinary taurine was determined to be
      2.42 +/- 0.08 MUM (confidence level, 95%; RSD, 1.05%; n = 4) with a recovery of
      98.92-109.54% (n = 3). These results demonstrate the inkjet injection system we
      developed has the potential to revolutionize capillary electrophoretic separation
      in practical and commercial applications that require an automated accurate
      injection system.

PMID- 23153060
TI  - Several steps/day indicators predict changes in anthropometric outcomes: HUB City
      Steps.
AB  - BACKGROUND: Walking for exercise remains the most frequently reported leisure
      time activity, likely because it is simple, inexpensive, and easily incorporated
      into most people's lifestyle. Pedometers are simple, convenient, and economical
      tools that can be used to quantify step-determined physical activity. Few studies
      have attempted to define the direct relationship between dynamic changes in
      pedometer-determined steps/day and changes in anthropometric and clinical
      outcomes. Hence, the objective of this secondary analysis was to evaluate the
      utility of several descriptive indicators of pedometer-determined steps/day for
      predicting changes in anthropometric and clinical outcomes using data from a
      community-based walking intervention, HUB City Steps, conducted in a southern,
      African American population. A secondary aim was to evaluate whether treating
      steps/day data for implausible values affected the ability of these data to
      predict intervention-induced changes in clinical and anthropometric outcomes.
      METHODS: The data used in this secondary analysis were collected in 2010 from 269
      participants in a six-month walking intervention targeting a reduction in blood
      pressure. Throughout the intervention, participants submitted weekly steps/day
      diaries based on pedometer self-monitoring. Changes (six-month minus baseline) in
      anthropometric (body mass index, waist circumference, percent body fat [%BF], fat
      mass) and clinical (blood pressure, lipids, glucose) outcomes were evaluated.
      Associations between steps/day indicators and changes in anthropometric and
      clinical outcomes were assessed using bivariate tests and multivariable linear
      regression analysis which controlled for demographic and baseline covariates.
      RESULTS: Significant negative bivariate associations were observed between
      steps/day indicators and the majority of anthropometric and clinical outcome
      changes (r = -0.3 to -0.2: P < 0.05). After controlling for covariates in the
      regression analysis, only the relationships between steps/day indicators and
      changes in anthropometric (not clinical) outcomes remained significant. For
      example, a 1,000 steps/day increase in intervention mean steps/day resulted in a
      0.1% decrease in %BF. Results for the three pedometer datasets (full, truncated,
      and excluded) were similar and yielded few meaningful differences in
      interpretation of the findings. CONCLUSIONS: Several descriptive indicators of
      steps/day may be useful for predicting anthropometric outcome changes. Further,
      manipulating steps/day data to address implausible values has little overall
      effect on the ability to predict these anthropometric changes.

PMID- 23153062
TI  - Effects of neuromuscular electrostimulation in patients with heart failure
      admitted to ward.
AB  - BACKGROUND: Neuromuscular electrostimulation has become a promising issue in
      cardiovascular rehabilitation. However there are few articles published in the
      literature regarding neuromuscular electrostimulation in patients with heart
      failure during hospital stay. METHODS: This is a randomized controlled pilot
      trial that aimed to investigate the effect of neuromuscular electrostimulation in
      the walked distance by the six-minute walking test in 30 patients admitted to
      ward for heart failure treatment in a tertiary cardiology hospital. Patients in
      the intervention group performed a conventional rehabilitation and neuromuscular
      electrostimulation. Patients underwent 60 minutes of electrostimulation (wave
      frequency was 20 Hz, pulse duration of 20 us) two times a day for consecutive
      days until hospital discharge. RESULTS: The walked distance in the six-minute
      walking test improved 75% in the electrostimulation group (from 379.7 +/- 43.5 to
      372.9 +/- 46.9 meters to controls and from 372.9 +/- 62.4 to 500 +/- 68 meters to
      electrostimulation, p<0.001). On the other hand, the walked distance in the
      control group did not change. CONCLUSION: The neuromuscular electrostimulation
      group showed greater improvement in the walked distance in the six-minute walking
      test in patients admitted to ward for compensation of heart failure.

PMID- 23153063
TI  - CLARITY - ChiLdhood Arthritis Risk factor Identification sTudY.
AB  - BACKGROUND: The aetiology of juvenile idiopathic arthritis (JIA) is largely
      unknown. We have established a JIA biobank in Melbourne, Australia called CLARITY
      - ChiLdhood Arthritis Risk factor Identification sTudY, with the broad aim of
      identifying genomic and environmental disease risk factors. We present here study
      protocols, and a comparison of socio-demographic, pregnancy, birth and early life
      characteristics of cases and controls collected over the first 3 years of the
      study. METHODS: Cases are children aged <=18 years with a diagnosis of JIA by 16
      years. Controls are healthy children aged <=18 years, born in the state of
      Victoria, undergoing a minor elective surgical procedure. Participant families
      provide clinical, epidemiological and environmental data via questionnaire, and a
      blood sample is collected. RESULTS: Clinical characteristics of cases (n = 262)
      are similar to those previously reported. Demographically, cases were from
      families of higher socio-economic status. After taking this into account, the
      residual pregnancy and perinatal profiles of cases were similar to control
      children. No case-control differences in breastfeeding commencement or duration
      were detected, nor was there evidence of increased case exposure to tobacco smoke
      in utero. At interview, cases were less likely to be exposed to active parental
      smoking, but disease-related changes to parent behaviour may partly underlie
      this. CONCLUSIONS: We show that, after taking into account socio-economic status,
      CLARITY cases and controls are well matched on basic epidemiological
      characteristics. CLARITY represents a new study platform with which to generate
      new knowledge as to the environmental and biological risk factors for JIA.

PMID- 23153064
TI  - An arrayed RNA interference genome-wide screen identifies candidate genes
      involved in the MicroRNA 21 biogenesis pathway.
AB  - MicroRNAs (miRNAs) are evolutionary conserved noncoding molecules that regulate
      gene expression. They influence a number of diverse biological functions, such as
      development and differentiation. However, their dysregulation has been shown to
      be associated with disease states, such as cancer. Genes and pathways regulating
      their biogenesis remain unknown and are highly sought after. For this purpose, we
      have validated a multiplexed high-content assay strategy to screen for such
      modulators. Here, we describe its implementation that makes use of a cell-based
      gain-of-function reporter assay monitoring enhanced green fluorescent protein
      expression under the control of miRNA 21 (miR-21); combined with measures of both
      cell metabolic activities through the use of Alamar Blue and cell death through
      imaged Hoechst-stained nuclei. The strategy was validated using a panel of known
      genes and enabled us to successfully progress to and complete an arrayed genome
      wide short interfering RNA (siRNA) screen against the Ambion Silencer Select v4.0
      library containing 64,755 siRNA duplexes covering 21,565 genes. We applied a high
      stringency hit analysis method, referred to as the Bhinder-Djaballah analysis
      method, leading to the nomination of 1,273 genes as candidate inhibitors of the
      miR-21 biogenesis pathway; after several iterations eliminating those genes with
      only one active duplex and those enriched in seed sequence mediated off-target
      effects. Biological classifications revealed four major control junctions among
      them vesicular transport via clathrin-mediated endocytosis. Altogether, our
      screen has uncovered a number of novel candidate regulators that are potentially
      good druggable targets allowing for the discovery and development of small
      molecules for regulating miRNA function.

PMID- 23153065
TI  - Riboflavin accumulation and characterization of cDNAs encoding lumazine synthase
      and riboflavin synthase in bitter melon (Momordica charantia).
AB  - Riboflavin (vitamin B2) is the universal precursor of the coenzymes flavin
      mononucleotide and flavin adenine dinucleotide--cofactors that are essential for
      the activity of a wide variety of metabolic enzymes in animals, plants, and
      microbes. Using the RACE PCR approach, cDNAs encoding lumazine synthase (McLS)
      and riboflavin synthase (McRS), which catalyze the last two steps in the
      riboflavin biosynthetic pathway, were cloned from bitter melon (Momordica
      charantia), a popular vegetable crop in Asia. Amino acid sequence alignments
      indicated that McLS and McRS share high sequence identity with other orthologous
      genes and carry an N-terminal extension, which is reported to be a plastid
      targeting sequence. Organ expression analysis using quantitative real-time RT PCR
      showed that McLS and McRS were constitutively expressed in M. charantia, with the
      strongest expression levels observed during the last stage of fruit ripening
      (stage 6). This correlated with the highest level of riboflavin content, which
      was detected during ripening stage 6 by HPLC analysis. McLS and McRS were highly
      expressed in the young leaves and flowers, whereas roots exhibited the highest
      accumulation of riboflavin. The cloning and characterization of McLS and McRS
      from M. charantia may aid the metabolic engineering of vitamin B2 in crops.

PMID- 23153066
TI  - Gene and functional up-regulation of the BCRP/ABCG2 transporter in hepatocellular
      carcinoma.
AB  - BACKGROUND: The Breast Cancer Resistance Protein (BCRP/ABCG2) is one member of
      ABC transporters proteins super family responsible of drug resistance. Since data
      on ABCG2 expression in liver malignances are scanty, here we report the
      expression of ABCG2 in adult human hepatocellular carcinoma (HCC) in both in vivo
      and in vitro models with different degree of malignancy. METHODS: In cell lines
      derived from human hepatocellular carcinoma, ABCG2 gene expression was assessed
      by reverse transcription quantitative real time PCR and function by Hoechst 33342
      efflux assay; protein content was assessed by SDS-PAGE Western blot. RESULTS:
      ABCG2 expression was found to be highest in the most undifferentiated cell lines,
      and this was related with a higher functional activity. ABCG2 expression was
      sensitive to antineoplastic drugs since exposure to 5 MUM doxorubicin for 24
      hours resulted in significant up-regulations of ABCG2 in all cell lines,
      particularly in those lines with low basal ABCG2 expression (p<0.01). The gene
      expression was also investigated in 51 adult liver tissues with HCC and related
      cirrhosis; normal liver tissue was used as control. ABCG2 gene expression was
      higher in HCC than both cirrhotic paired tissue and normal tissue. This up
      regulation was greater (p<0.05) in pathological poorly differentiated grade G3/G4
      than in well-differentiated G1/G2 HCC. CONCLUSIONS: Our results suggest a
      correlation of ABCG2 gene expression and differentiation stage both in human and
      HCC derived cell lines. The rapid up-regulation of ABCG2 to exposure to
      doxorubicin emphasizes the importance of this transporter in accounting for drug
      resistance in liver tumors.

PMID- 23153067
TI  - Analytical approaches for studying transporters, channels and porins.

PMID- 23153068
TI  - Proteomic analysis of alterations induced by perinatal hypoxic-ischemic brain
      injury.
AB  - Perinatal hypoxic-ischemic brain injury is an important cause of neurological
      deficits still causing mortality and morbidity in the early period of life. As
      efficient clinical or pharmaceutical strategies to prevent or reduce the outcome
      of perinatal hypoxic-ischemic brain damage are limited, the development of new
      therapies is of utmost importance. To evolve innovative therapeutic concepts,
      elucidation of the mechanisms contributing to the neurological impairments upon
      hypoxic-ischemic brain injury is necessary. Therefore, we aimed for the
      identification of proteins that are affected by hypoxic-ischemic brain injury in
      neonatal rats. To assess changes in protein expression two days after induction
      of brain damage, a 2D-DIGE based proteome analysis was performed. Among the
      proteins altered after hypoxic-ischemic brain injury, Calcineurin A, Coronin-1A,
      as well as GFAP were identified, showing higher expression in lesioned
      hemispheres. Validation of the changes in Calcineurin A expression by Western
      Blot analysis demonstrated several truncated forms of this protein generated by
      limited proteolysis after hypoxia-ischemia. Further analysis revealed activation
      of calpain, which is involved in the limited proteolysis of Calcineurin. Active
      forms of Calcineurin are associated with the dephosphorylation of Darpp-32, an
      effect that was also demonstrated in lesioned hemispheres after perinatal brain
      injury.

PMID- 23153070
TI  - Electrochemical properties of interstrand cross-linked DNA duplexes labeled with
      Nile blue.
AB  - DNA molecules have attracted considerable attention as functional materials in
      various fields such as electrochemical sensors with redox-labeled DNA. However,
      the recently developed interstrand cross-link (ICL) technique for double-stranded
      DNA can adequately modify the electronic properties inside the duplex. Hence, the
      electrochemical investigation of ICL-DNA helps us to understand the electron
      transfer of redox-labeled DNA at an electrode surface, which would develop useful
      sensors. In this study, the first insight into this matter is presented. We
      prepared 17-mer DNA duplexes incorporating Nile blue (NB-DNA) at one end as a
      redox marker and a disulfide tether at the other end for immobilization onto an
      electrode. The duplexes were covalently cross-linked by bifunctional cross
      linkers that utilize either a propyl or naphthalene residue to replace a base
      pair. Their electrochemical responses at the electrode surface were compared to
      evaluate the effect of the ICL on the electron-transfer reactions of the redox
      labeled DNA duplexes. A direct transfer of electrons between NB and the electrode
      was observed for a standard DNA, as previously reported, whereas interstrand
      cross-linked DNA (CL-DNA) strands showed a decrease in the direct electron
      transfer pathway. This is expected to result from constraining the elastic
      bending/flexibility of the duplex caused by the covalent cross-links.
      Interestingly, the CL-DNA incorporating naphthalene residues exhibited additional
      voltammetric peaks derived from DNA-mediated electron transfer (through base pi
      stacking), which was not observed in the mismatched CL-DNA. The present results
      indicate that the ICL significantly affects electron transfer in the redox
      labeled DNA at the electrode and can be an important determinant for
      electrochemical signaling in addition to its role in stabilizing the duplex
      structure.

PMID- 23153069
TI  - Evidence for conserved post-transcriptional roles of unitary pseudogenes and for
      frequent bifunctionality of mRNAs.
AB  - BACKGROUND: Recent reports have highlighted instances of mRNAs that, in addition
      to coding for protein, regulate the abundance of related transcripts by altering
      microRNA availability. These two mRNA roles - one mediated by RNA and the other
      by protein - are inter-dependent and hence cannot easily be separated. Whether
      the RNA-mediated role of transcripts is important, per se, or whether it is a
      relatively innocuous consequence of competition by different transcripts for
      microRNA binding remains unknown. RESULTS: Here we took advantage of 48 loci that
      encoded proteins in the earliest eutherian ancestor, but whose protein-coding
      capability has since been lost specifically during rodent evolution. Sixty-five
      percent of such loci, which we term 'unitary pseudogenes', have retained their
      expression in mouse and their transcripts exhibit conserved tissue expression
      profiles. The maintenance of these unitary pseudogenes' spatial expression
      profiles is associated with conservation of their microRNA response elements and
      these appear to preserve the post-transcriptional roles of their protein-coding
      ancestor. We used mouse Pbcas4, an exemplar of these transcribed unitary
      pseudogenes, to experimentally test our genome-wide predictions. We demonstrate
      that the role of Pbcas4 as a competitive endogenous RNA has been conserved and
      has outlived its ancestral gene's loss of protein-coding potential. CONCLUSIONS:
      These results show that post-transcriptional regulation by bifunctional mRNAs can
      persist over long evolutionary time periods even after their protein coding
      ability has been lost.

PMID- 23153071
TI  - Reactivity of diphenylpropynone derivatives toward metal-associated amyloid-beta
      species.
AB  - In Alzheimer's disease (AD), metal-associated amyloid-beta (metal-Abeta) species
      have been suggested to be involved in neurotoxicity; however, their role in
      disease development is still unclear. To elucidate this aspect, chemical reagents
      have been developed as valuable tools for targeting metal-Abeta species,
      modulating the interaction between the metal and Abeta, and subsequently altering
      metal-Abeta reactivity. Herein, we report the design, preparation,
      characterization, and reactivity of two diphenylpropynone derivatives (DPP1 and
      DPP2) composed of structural moieties for metal chelation and Abeta interaction
      (bifunctionality). The interactions of these compounds with metal ions and Abeta
      species were confirmed by UV-vis, NMR, mass spectrometry, and docking studies.
      The effects of these bifunctional molecules on the control of in vitro metal-free
      and metal-induced Abeta aggregation were investigated and monitored by gel
      electrophoresis and transmission electron microscopy (TEM). Both DPP1 and DPP2
      showed reactivity toward metal-Abeta species over metal-free Abeta species to
      different extents. In particular, DPP2, which contains a dimethylamino group,
      exhibited greater reactivity with metal-Abeta species than DPP1, suggesting a
      structure-reactivity relationship. Overall, our studies present a new
      bifunctional scaffold that could be utilized to develop chemical reagents for
      investigating metal-Abeta species in AD.

PMID- 23153072
TI  - Cooperative stabilization of Zn(2+):DNA complexes through netropsin binding in
      the minor groove of FdU-substituted DNA.
AB  - The simultaneous binding of netropsin in the minor groove and Zn(2+) in the major
      groove of a DNA hairpin that includes 10 consecutive FdU nucleotides at the 3'
      terminus (3'FdU) was demonstrated based upon NMR spectroscopy, circular dichroism
      (CD), and computational modeling studies. The resulting Zn(2+)/netropsin: 3'FdU
      complex had very high thermal stability with aspects of the complex intact at 85 
      degrees C, conditions that result in complete dissociation of Mg(2+) complexes.
      CD and (19)F NMR spectroscopy were consistent with Zn(2+) binding in the major
      groove of the DNA duplex and utilizing F5 and O4 of consecutive FdU nucleotides
      as ligands with FdU nucleotides hemi-deprotonated in the complex. Netropsin is
      bound in the minor groove of the DNA duplex based upon 2D NOESY data
      demonstrating contacts between AH2 (1)H and netropsin (1)H resonances. The
      Zn(2+)/netropsin: 3'FdU complex displayed increased cytotoxicity towards PC3
      prostate cancer (PCa) cells relative to the constituent components or separate
      complexes (e.g. Zn(2+):3'FdU) indicating that this new structural motif may be
      therapeutically useful for PCa treatment. An animated interactive 3D complement
      (I3DC) is available in Proteopedia at http://proteopedia.org/w/Journal:JBSD:32. 

PMID- 23153073
TI  - Long-term functional outcome of tibial plateau leveling osteotomy versus
      extracapsular repair in a heterogeneous population of dogs.
AB  - OBJECTIVE: To compare the long-term outcome of tibial plateau leveling osteotomy
      (TPLO) and extracapsular repair (ECR) for treatment of a ruptured cranial
      cruciate ligament (RCCL). STUDY DESIGN: Prospective clinical trial. ANIMALS:
      Normal adult dogs (control, n = 79); dogs with unilateral CCL disease (n = 38).
      METHODS: Dogs had TPLO (n = 15) or ECR (n = 23) for treatment of RCCL. Force
      plate gait analysis was performed for the control group at one time point and for
      treatment groups at serial points: preoperatively, 2 weeks, 8 weeks, 6 and 12
      months postoperatively. Symmetry indices (SIs) were calculated between operated
      and unoperated pelvic limb for ground reaction forces (GRFs), including peak
      vertical force (PVF), contact time (CT), and vertical impulse (VI). GRFs of the
      treatment groups and control group were compared using a general linear model and
      Kaplan-Meier survival analysis. RESULTS: At 8 weeks, for PVF and VI, the TPLO
      group had more symmetric limb loading than the ECR group at the walk and trot.
      SIs of the TPLO group were not different from the control group by 6 months to 1
      year postoperatively. SIs for the ECR group were less symmetrical than the
      control group at all time periods. Using survival analysis, median time to normal
      function was no different at the walk between groups, but was shorter for the
      TPLO group for VI and PVF. CONCLUSIONS: Dogs achieved normal limb loading faster
      after TPLO than ECR. TPLO resulted in operated limb function that was
      indistinguishable from the control population by 1 year postoperatively.

PMID- 23153074
TI  - Fate of trace elements during the combustion of phytoremediation wood.
AB  - We investigated the fate of trace elements (TE) in poplar wood on the conversion
      of biomass to heat in a 0.2 MW combustion unit equipped with a fabric filter. The
      phytoremediation wood was harvested from a TE-contaminated agricultural site
      planted with a high-density poplar stand. The combustion technology used in the
      present experiment allows for an efficient separation of the various ash
      fractions. The combustion process concentrates Cu, Cr, and Ni in the bottom ash,
      heat exchanger ash, and cyclone ash fractions. Therefore, the impact of the
      fabric filter is negligible for these elements. Conversely, Cd, Pb, and Zn are
      significantly recovered in the emission fraction in the absence of the fabric
      filter above the emission limits. The use of a fabric filter will allow the
      concentration of these three TEs in the ashes collected below the filter, thus
      complying with all regulatory thresholds, i.e., those from the large combustion
      plant EU directive. Because the TE concentrations in the different fractions
      differed significantly, it is recommended that these fractions be treated
      separately, especially when recycling of ashes from phytoremediation wood through
      application in agriculture is envisaged.

PMID- 23153075
TI  - Erectile dysfunction diagnosis and treatment as a means to improve medication
      adherence and optimize comorbidity management.
AB  - INTRODUCTION: Optimal pharmacologic management of diseases comorbid with erectile
      dysfunction (ED), such as cardiovascular disease, depression, diabetes,
      dyslipidemia, hypertension, and benign prostatic hyperplasia/lower urinary tract
      symptoms (BPH/LUTS), is dependent upon long-term treatment compliance and may be
      complicated by poor adherence to medication use. ED may contribute to poor
      adherence to medication use because poor quality erectile function may be an
      unwanted adverse effect of antihypertensives, antidepressants, and 5-alpha
      reductase inhibitors for treatment of BPH/LUTS. Diminished erectile spontaneity,
      rigidity, and/or sustaining capability also negatively affects mood, self-esteem,
      and confidence, which compromise motivation to be compliant with medications that
      treat diseases comorbid with ED. AIM: Literature review was performed to explore
      the role of ED diagnosis and effective treatment in enhancing overall management
      of selected ED comorbidities, highlighting the role of medication adherence.
      METHODS: Several PubMed searches were performed. RESULTS: Diagnosis and
      successful treatment of concomitant ED may promote improved adherence and
      management of comorbid diseases. Concomitant ED management may improve treatment
      outcome, decrease healthcare costs, and possibly prevent or even improve
      deterioration in medical conditions comorbid with ED. Because ED is a silent
      marker and predictor of comorbidities, especially cardiovascular disease, earlier
      diagnosis of ED may provide an opportunity to prevent future cardiovascular
      events. In men presenting with complaints of ED, screening for, monitoring, and
      appropriately treating diseases that are comorbid with ED is essential. Screening
      for and appropriately treating ED is important for enhanced life quality and
      improved motivation in men with existing ED comorbidities or risk factors.
      CONCLUSIONS: Appropriate management of ED and its risk factors may have
      beneficial effects on diseases that are comorbid with ED, and vice versa, most
      likely via shared pathophysiological pathways. Clinicians may need to consider
      men's health overall, of which sexual health is a central component, in order to
      provide optimal disease management.

PMID- 23153076
TI  - Selection bias in family reports on end of life with dementia in nursing homes.
AB  - BACKGROUND: Selective participation in retrospective studies of families
      recruited after the patient's death may threaten generalizability of reports on
      end-of-life experiences. OBJECTIVES: To assess possible selection bias in
      retrospective study of dementia at the end of life using family reports. METHODS:
      Two physician teams covering six nursing home facilities in the Netherlands
      reported on 117 of 119 consecutive decedents within two weeks after death unaware
      of after-death family participation in the study. They reported on
      characteristics; treatment and care; overall patient outcomes such as comfort,
      nursing care, and outcomes; and their own perspectives on the experience. We
      compared results between decedents with and without family participation.
      RESULTS: The family response rate was 55%. There were no significant differences
      based on participation versus nonparticipation in demographics and other nursing
      home resident characteristics, treatment and care, or overall resident outcome.
      However, among participating families, physicians perceived higher-quality
      aspects of nursing care and outcome, better consensus between staff and family on
      treatment, and a more peaceful death. Participation was less likely with
      involvement of a new family member in the last month. CONCLUSIONS: Families may
      be more likely to participate in research with more harmonious teamwork in end-of
      life caregiving. Where family participation is an enrollment criterion, comparing
      demographics alone may not capture possible selection bias, especially in more
      subjective measures. Selection bias toward more positive experiences, which may
      include the physician's and probably also the family's experiences, should be
      considered if representativeness is aimed for. Future work should address
      selection bias in other palliative settings and countries, and with prospective
      recruitment.

PMID- 23153077
TI  - Ovarian benign clear cell adenofibroma in a patient with premature ovarian
      failure after 8-year hormone replacement therapy.
AB  - Ovary benign clear cell adenofibroma (CCAF) is extremely rare. Here, we reported
      a 38-year-old woman with CCAF who was given sequential cyclic hormone replacement
      therapy for eight years due to premature ovarian failure (POF). At operation, we
      found adenofibromas in both ovaries and well encapsulated. The cut surface was
      cystic and solid in appearance, and multilocular cysts embedded in hard stroma.
      Determination of sex hormone levels in the fluid of cysts of the ovary showed
      normal level. Clear cell cystadenofibroma proliferation was found in ovarian
      stroma while atrophy in ovarian cortex. Histological examination revealed that
      the glands were lined by 1 or 2 layers of hobnail cells with scant to moderate
      pale or clear cytoplasm. The nuclei were small uniform, and flat to round.
      Neither primary follicles nor secondary follicles were observed in ovary cortex.
      Immunohistochemical results showed that EMA and p53 were positive while
      Calretinin was negative. In this article, we reviewed literatures and analyzed
      both clinical and pathological features of ovary benign clear cell adenofibromas.

PMID- 23153079
TI  - The impact of cognitive anchors on information-sharing behavior.
AB  - In computer-supported information exchange, people frequently tend to withhold
      their own information and free-ride on the others' contributions. In doing so,
      they save costs (time and effort) and maximize their own benefit. However, if
      everyone behaved in this way, there would be no information sharing at all. In
      this experiment, we tested if the presentation of a random number could serve as
      a cognitive anchor and influence the amount of shared information. The
      experimental setting had all the features of an information-exchange dilemma.
      Before participants could share information, a random generator presented a
      random number. It was found that this number served as a cognitive anchor and
      influenced both the participants' behavioral intentions and their actual
      behavior. Particularly, the high anchor increased cooperation, even though
      enhanced cooperation was obviously detrimental to the individual's own benefit.

PMID- 23153078
TI  - P2TF: a comprehensive resource for analysis of prokaryotic transcription factors.
AB  - BACKGROUND: Transcription factors (TFs) are DNA-binding proteins that regulate
      gene expression by activating or repressing transcription. Some have housekeeping
      roles, while others regulate the expression of specific genes in response to
      environmental change. The majority of TFs are multi-domain proteins, and they can
      be divided into families according to their domain organisation. There is a need
      for user-friendly, rigorous and consistent databases to allow researchers to
      overcome the inherent variability in annotation between genome sequences.
      DESCRIPTION: P2TF (Predicted Prokaryotic Transcription Factors) is an integrated
      and comprehensive database relating to transcription factor proteins. The current
      version of the database contains 372,877 TFs from 1,987 completely sequenced
      prokaryotic genomes and 43 metagenomes. The database provides annotation,
      classification and visualisation of TF genes and their genetic context, providing
      researchers with a one-stop shop in which to investigate TFs. The P2TF database
      analyses TFs in both predicted proteomes and reconstituted ORFeomes, recovering
      approximately 3% more TF proteins than just screening predicted proteomes. Users
      are able to search the database with sequence or domain architecture queries, and
      resulting hits can be aligned to investigate evolutionary relationships and
      conservation of residues. To increase utility, all searches can be filtered by
      taxonomy, TF genes can be added to the P2TF cart, and gene lists can be exported
      for external analysis in a variety of formats. CONCLUSIONS: P2TF is an open
      resource for biologists, allowing exploration of all TFs within prokaryotic
      genomes and metagenomes. The database enables a variety of analyses, and results
      are presented for user exploration as an interactive web interface, which
      provides different ways to access and download the data. The database is freely
      available at http://www.p2tf.org/.

PMID- 23153080
TI  - Effects of gender and physical attractiveness on visual attention to Facebook
      profiles.
AB  - The current study examined viewers' gaze while observing Facebook profiles of
      strangers varying in gender and physical attractiveness. Fifty-one participants
      viewed four Facebook profiles, a physically attractive and unattractive
      individual of each gender. Participants' eye movements were tracked as they
      viewed each profile for 60 seconds. Results showed that participants paid more
      attention to the physical appearance (main profile photograph) of female than of
      male profile owners and to the personal information (likes and interests) of male
      than to female profile owners. Participants spent more time focusing on
      information that was irrelevant to forming an impression of the profile owner
      (advertisements) when viewing the profiles of unattractive than attractive
      individuals, suggesting that they made a greater effort to learn about these
      individuals.

PMID- 23153081
TI  - Excitation spectra of cation and anion radicals of several unsaturated
      hydrocarbons: symmetry adapted cluster-configuration interaction theoretical
      study.
AB  - Excitation spectra of cation and anion radicals of unsaturated hydrocarbons,
      hexatriene(+/-), octatetraene(+/-), cyclopentadiene(+), 1,3-cyclohexadiene(+),
      and naphthalene(+/-), were studied by the symmetry adapted cluster-configuration
      interaction (SAC-CI) method. The calculated results reasonably reproduced the
      experimental spectra observed by one of the authors (T.S.) and gave reasonable
      assignments. The two bands observed in the experimental spectra were assigned to
      pi-pi(SOMO) and pi(SOMO)-pi* for the cation radicals and pi*(SOMO)-pi* and pi
      pi*(SOMO) for the anion radicals, in order of increasing energy, except for
      naphthalene(+/-). The four bands of naphthalene(+) originated from pi-pi(SOMO),
      pi-pi(SOMO), pi(SOMO)-pi*, and pi(SOMO)-pi* and those of naphthalene(-)
      originated from pi*(SOMO)-pi*, pi*(SOMO)-pi*, pi-pi*(SOMO), pi*(SOMO)-vpi*, and
      pi-pi*(SOMO), in order of increasing energy. The SOMO orbitals were involved in
      the intense bands of both cation and anion radicals. Moreover, the ionization
      energies (IEs) and electron affinities (EAs) of these hydrocarbons were in good
      agreement with the experimental values, whereas the EAs of hexatriene and
      octatetraene were predicted to be negative and positive, respectively. The
      calculated IE + EA values were nearly constant for the three pi-pi* pairing
      states of hexatriene(+/-), octatetraene(+/-), and naphthalene(+/-), indicating
      that the pairing theorem is valid even at the SAC-CI level.

PMID- 23153082
TI  - Australia's notifiable disease status, 2010: annual report of the National
      Notifiable Diseases Surveillance System.
AB  - In 2010, 65 diseases and conditions were nationally notifiable in Australia.
      States and territories reported a total of 209,079 notifications of communicable
      diseases to the National Notifiable Diseases Surveillance System, a decrease of
      12% on the number of notifications in 2009. This decrease was largely due to a
      reduction of influenza compared with the influenza A(H1N1) pandemic 2009. In
      2010, the most frequently notified diseases were sexually transmissible
      infections (86,620 notifications, 41.4% of total notifications), vaccine
      preventable diseases (61,964 notifications, 29.6% of total notifications), and
      gastrointestinal diseases (31,548 notifications, 15.1% of total notifications).
      There were 18,302 notifications of bloodborne diseases; 8,244 notifications of
      vectorborne diseases; 1,866 notifications of other bacterial infections; 532
      notifications of zoonoses and 3 notifications of quarantinable diseases.

PMID- 23153083
TI  - Arboviral diseases and malaria in Australia, 2009-10: annual report of the
      National Arbovirus and Malaria Advisory Committee.
AB  - The National Notifiable Diseases Surveillance System received 7,609 notified
      cases of disease transmitted by mosquitoes for the season 1 July 2009 to 30 June
      2010. The alphaviruses Barmah Forest virus and Ross River virus, accounted for
      6,546 (79%) of these notifications during the 2009-10 season. There were 37
      notifications of dengue virus infection locally-acquired from North Queensland
      and 581 notified cases in Australia that resulted from overseas travel. This
      number of overseas acquired cases continues to rise each year due to increasing
      disease activity in the Asia-Pacific region and increased air travel. Detection
      of flavivirus seroconversions in sentinel chicken flocks across Australia
      provides an early warning of increased levels of Murray Valley encephalitis virus
      and Kunjin virus activity. Flavivirus activity was detected in western and
      northern Australia in 2009-10, which prompted public health action. No human
      cases of Murray Valley encephalitis virus infection were notified, while there
      were 2 cases of Kunjin virus infection notified. There were no notifications of
      locally-acquired malaria in Australia and 429 notifications of overseas-acquired
      malaria during the 2009-10 season. This annual report presents information of
      diseases transmitted by mosquitoes in Australia and notified to the National
      Notifiable Diseases Surveillance System.

PMID- 23153084
TI  - Tuberculosis notifications in Australia, 2008 and 2009.
AB  - The National Notifiable Diseases Surveillance System received 1,194 tuberculosis
      (TB) notifications in 2008 and 1,322 notifications in 2009. The incidence of TB
      in Australia was 5.6 cases per 100,000 population in 2008 and 6.0 per 100,000 in
      2009, similar to rates since 1986. In both 2008 and 2009, more than 85% of cases
      occurred in the overseas-born population. The incidence in the Australian-born
      Indigenous population was 6.2 per 100,000 population in 2008 and 4.8 per 100,000
      in 2009. By contrast, the incidence of TB in the Australian-born non-Indigenous
      population was 0.9 per 100,000 in both 2008 and 2009. Household or other close
      contact with TB or past residence in a high risk country were the most commonly
      reported risk factors for TB infection. In 2008, 83 cases of TB were reported in
      health care workers; this decreased to 75 in 2009. There were no reports of TB
      transmission in Australian health care settings. Outcome data of the 2007 and
      2008 TB cohort indicate that treatment success was attained in more than 95% of
      cases. As Australia continues to contribute to global TB control it is important
      to maintain good centralised reporting of TB to identify populations at risk and
      for early detection of reversal in trends in TB.

PMID- 23153085
TI  - Surveillance of antibiotic resistance in Neisseria gonorrhoeae in the WHO Western
      Pacific and South East Asian Regions, 2010.
AB  - The World Health Organization (WHO) Gonococcal Antimicrobial Surveillance
      Programme (GASP) has conducted continuous surveillance of antimicrobial
      resistance in Neisseria gonorrhoeae in the WHO Western Pacific Region (WPR) to
      optimise antibiotic treatment and control of gonococcal disease since 1992. From
      2007, this has been enhanced by the inclusion of data from the WHO South East
      Asian Region (SEAR). Over time, there has been recruitment of additional centres
      in both regions. This report provides an analysis of antimicrobial resistance in
      N. gonorrhoeae in the WHO WPR and SEAR derived from results of the 2010 GASP
      surveillance. In 2010 there were 9,744 N. gonorrhoeae isolates examined for their
      susceptibility to one or more of the antibiotics used for the treatment of
      gonorrhoea, incorporating External Quality Assurance controlled methods, from
      reporting centres in 19 countries and/or jurisdictions. A high proportion of
      penicillin and quinolone resistance was again detected amongst isolates tested in
      the 'Asian' countries of WHO WPR and SEAR. In contrast, lower levels of
      penicillin and quinolone resistance were reported from the Pacific Islands of
      Fiji and New Caledonia. The proportion of gonococci reported as having 'decreased
      susceptibility' to the third-generation cephalosporin antibiotic ceftriaxone
      varied widely, ranging from 1.3% to 55.8%. There is a continued need for revision
      and clarification of some of the in vitro criteria that are currently used to
      categorise the clinical importance of gonococci with different ceftriaxone and
      oral cephalosporin MIC levels, and to relate these to treatment outcome.
      Azithromycin resistance was very low in most countries reporting, except in
      Mongolia where it was 34%. The number of instances of spectinomycin resistance
      remained low. A high proportion of strains tested continued to exhibit high-level
      plasmid mediated resistance to tetracyclines. The continuing emergence and spread
      of antibiotic resistant gonococci in and from the WHO WPR and SEAR underlines the
      importance of the maintenance and expansion of surveillance programs such as
      GASP, which are essential for disease control.

PMID- 23153086
TI  - An outbreak of Salmonella Typhimurium linked to a kebab takeaway shop.
AB  - This paper describes the public health investigation and response to a Salmonella
      Typhimurium outbreak in June 2010 in the Central Coast of New South Wales. Two
      complaints from people with acute gastrointestinal illness pointed to food from a
      kebab takeaway shop as the cause of their illness. Liaison between public health
      and food authorities ensured timely epidemiological and environmental
      investigations leading to prompt identification and elimination of the point
      source. A case series investigation identified 45 outbreak cases including 31
      laboratory-confirmed and 14 epidemiologically-linked cases. The food vehicles
      identified were hommus and tabouli--93% of cases reported having one or both
      items in their kebab. S. Typhimurium with the same MLVA type was found in stool
      specimens from outbreak cases and in food (including hommus and tabouli) and
      environmental samples collected at the kebab takeaway shop. Education of
      commercial food handlers, reduction of poultry meat contamination and
      collaboration between public health and food authorities to ensure prompt
      identification and control of outbreaks are important strategies to reduce
      Salmonella related illness.

PMID- 23153087
TI  - Imported malaria in the Northern Territory, Australia--428 consecutive cases.
AB  - Malaria is a notifiable disease in Australia with an average of 600 notifications
      per year in returned travellers or newly arrived refugees, migrants and visitors.
      Although endemic disease has been eliminated from the tropical north of
      Australia, the region remains malaria receptive due to the presence of efficient
      mosquito vectors. This study analyses enhanced surveillance data collected by the
      Centre for Disease Control on all cases of malaria notified in the Northern
      Territory from 1 January 2000 to 31 December 2010. There were 428 malaria
      episodes notified that occurred in 391 individuals with a median age of 26 years.
      Of these, 71.4% were male, 40.5% were Australian nationals and 38.0% were
      prescribed chemoprophylaxis. Primary infection consisted of 196 (51.3%) cases of
      Plasmodium falciparum, 165 (43.2%) P. vivax, 2 (0.5%) P. ovale, 1 (0.3%) P.
      malariae and 18 were mixed infections. There were 46 episodes of relapsed
      infection. Residents of non-malarious countries were most likely to have acquired
      primary infection in East Timor (40.6%), Papua New Guinea (27.8%), Indonesia
      (18.7%) and Africa (6.4%). Primary infection was diagnosed after a median 19 days
      (interquartile range (IQR) 7-69) after arrival in Australia for cases of P. vivax
      compared with 4 days for P. falciparum (IQR 2-11). Screening protocols led to the
      diagnosis of 27.2% of cases. Eighty-seven per cent of patients were admitted to
      hospital at the time of their malaria diagnosis with median duration of 3 days
      (IQR 2-4) and one patient died. Resettlement of people from endemic countries, as
      well as military and civilian activities, influences the prevailing notification
      rates and Plasmodium species type.

PMID- 23153088
TI  - Supplementary report: Surveillance of adverse events following immunisation among
      children aged less than seven years in Australia, 1 January to 30 June 2011.

PMID- 23153089
TI  - Position statement on interferon-gamma release assays in the detection of latent
      tuberculosis infection.

PMID- 23153090
TI  - Under the (legal) radar screen: global health initiatives and international human
      rights obligations.
AB  - BACKGROUND: Given that many low income countries are heavily reliant on external
      assistance to fund their health sectors the acceptance of obligations of
      international assistance and cooperation with regard to the right to health
      (global health obligations) is insufficiently understood and studied by
      international health and human rights scholars. Over the past decade Global
      Health Initiatives, like the Global Fund to fight AIDS, Tuberculosis and Malaria
      (Global Fund) have adopted novel approaches to engaging with stakeholders in high
      and low income countries. This article explores how this experience impacted on
      acceptance of the international obligation to (help) fulfil the right to health
      beyond borders. METHODS: The authors conducted an extensive review of
      international human rights law literature, transnational legal process
      literature, global public health literature and grey literature pertaining to
      Global Health Initiatives. To complement this desk work and deepen their
      understanding of how and why different legal norms evolve the authors conducted
      19 in-depth key informant interviews with actors engaged with three stakeholders;
      the European Union, the United States and Belgium. The authors then analysed the
      interviews through a transnational legal process lens. RESULTS: Through according
      value to the process of examining how and why different legal norms evolve
      transnational legal process offers us a tool for engaging with the dynamism of
      developments in global health suggesting that operationalising global health
      obligations could advance the right to health for all. CONCLUSIONS: In many low
      income countries the health sector is heavily dependent on external assistance to
      fulfil the right to health of people thus it is vital that policies and tools for
      delivering reliable, long-term assistance are developed so that the right to
      health for all becomes more than a dream. Our research suggests that the Global
      Fund experience offers lessons to build on.

PMID- 23153091
TI  - Plasma jet desorption atomization-atomic fluorescence spectrometry and its
      application to mercury speciation by coupling with thin layer chromatography.
AB  - A novel plasma jet desorption atomization (PJDA) source was developed for atomic
      fluorescence spectrometry (AFS) and coupled on line with thin layer
      chromatography (TLC) for mercury speciation. An argon dielectric barrier
      discharge plasma jet, which is generated inside a 300 MUm quartz capillary,
      interacts directly with the sample being analyzed and is found to desorb and
      atomize surface mercury species rapidly. The effectiveness of this PJDA surface
      sampling technique was demonstrated by measuring AFS signals of inorganic Hg(2+),
      methylmercury (MeHg), and phenylmercury (PhHg) deposited directly on TLC plate.
      The detection limits of the proposed PJDA-AFS method for inorganic Hg(2+), MeHg,
      and PhHg were 0.51, 0.29, and 0.34 pg, respectively, and repeatability was 4.7%,
      2.2%, and 4.3% for 10 pg Hg(2+), MeHg, and PhHg. The proposed PJDA-AFS was also
      successfully coupled to TLC for mercury speciation. Under optimized conditions,
      the measurements of mercury dithizonate (Hg-D), methylmercury dithizonate (MeHg
      D), and phenylmercury dithizonate (PhHg-D) could be achieved within 3 min with
      detection limits as low as 8.7 pg. The combination of TLC with PJDA-AFS provides
      a simple, cost-effective, relatively high-throughput way for mercury speciation.

PMID- 23153092
TI  - The effect of physician's recommendation on seasonal influenza immunization in
      children with chronic diseases.
AB  - BACKGROUND: Despite recommendations by Health Authorities, influenza immunization
      coverage remains low in children with chronic diseases. Different medical
      providers involved in the management of children with chronic conditions may
      affect the pattern of influenza vaccine recommendations and coverage. The
      likelihood of vaccination by type of provider in children with chronic conditions
      is poorly understood. Therefore, the objectives of this study were to analyze the
      pattern and the effect of recommendations for seasonal influenza immunization
      provided by different physician profiles to families of children with chronic
      diseases and to measure the frequency of immunization in the study population.
      METHODS: We recruited children with chronic diseases aged 6 months-18 years who
      subsequently presented to specialty clinics for routine follow-up visits, during
      spring 2009, in three Italian Regions Families of children with chronic diseases
      were interviewed during routine visits at reference centers through a face-to
      face interview. We analyzed the following immunization predictors: having
      received a recommendation toward influenza immunization by a health provider;
      child's sex and age; mothers and fathers' age; parental education and employment;
      underlying child's disease; number of contacts with health providers in the
      previous year. Influenza immunization coverage was calculated as the proportion
      of children who received at least one dose of seasonal influenza vaccine in the
      previous season. We calculated prevalence ratios and we used a generalized linear
      model with Poisson family, log link and robust error variance to assess the
      effect of socio-demographic variables, underlying diseases, and recommendations
      provided by physicians on influenza immunization. RESULTS: We enrolled 275
      families of children with chronic diseases. Overall influenza coverage was 57.5%,
      with a low of 25% in children with neurological diseases and a high of 91.2% in
      those with cystic fibrosis. While 10.6% of children who did not receive any
      recommendation toward influenza immunization were immunized, among those who
      received a recommendation 87.5-94.7% did, depending on the health professional
      providing the recommendation. Receiving a recommendation by any provider is a
      strong predictor of immunization (PR = 8.5 95% CI 4.6;15.6) Most children
      received an immunization recommendation by a specialty (25.8%) or a family
      pediatrician (23.3%) and were immunized by a family pediatrician (58.7%) or a
      community vaccinator (55.2%). CONCLUSIONS: Receiving a specific recommendation by
      a physician is a strong determinant of being immunized against seasonal influenza
      in children with chronic diseases independently of other factors. Heterogeneity
      exists among children with different chronic diseases regarding influenza
      recommendation despite international guidelines. Increasing the frequency of
      appropriate recommendations toward influenza immunization by physicians is a
      single powerful intervention that may increase coverage in children with chronic
      conditions.

PMID- 23153094
TI  - Moving metabolomics from a data-driven science to an integrative systems science.
AB  - A report on the 7th annual Metabomeeting of the Metabolic Profiling Forum,
      University of Manchester, Manchester, UK, 25-27 September 2012. 

PMID- 23153093
TI  - In silico vs in vitro analysis of primer specificity for the detection of
      Gardnerella vaginalis, Atopobium vaginae and Lactobacillus spp.
AB  - BACKGROUND: Bacterial vaginosis (BV) is a common pathology of women in
      reproductive age that can lead to serious health complications, and is associated
      with shifts in the normal microflora from predominance of Lactobacillus spp. to a
      proliferation of other anaerobes such as G. vaginalis and A vaginae, which can be
      detected by PCR. The optimal PCR pathogen detection assay relies mainly on the
      specificity and sensitivity of the primers used. FINDINGS: Here we demonstrate
      that in silico analytical testing of primer specificity is not a synonym to in
      vitro analytical specificity by testing a range of published and newly designed
      primers with both techniques for the detection of BV-associated microorganisms.
      CONCLUSIONS: By testing primer in vitro specificity with a sufficient range of
      bacterial strains, we were able to design primers with higher specificity and
      sensitivity. Also by comparing the results obtained for the newly designed
      primers with other previously published primers, we confirmed that in silico
      analysis is not sufficient to predict in vitro specificity. As such care must be
      taken when choosing the primers for a detection assay.

PMID- 23153096
TI  - An English Translation of Joseph Luc Riopelle, MD, (Hotel-Dieu of Montreal), and
      Jean Paul Theriault (Hopital General of Verdun, Quebec, Canada): Sur une forme
      meconnue de sarcome des parties molles: le rhabdomyosarcome alveolaire
      (concerning an unrecognized form of sarcoma of the soft tissues: alveolar
      rhabdomyosarcoma). annales d'anatomie pathologique 1956;1:88-111.
AB  - We believe that this is the first translation into English of the first
      description, in French, of a disease previously unknown. JL Riopelle and JP
      Theriault, both pathologists, reviewed clinical and pathologic findings in six
      young patients with soft tissue tumors, and contributed autopsy information on
      four of the patients. Only one patient was initially correctly diagnosed with
      rhabdomyosarcoma; the other five initially had alternative diagnoses. Because of
      space limitations, we have condensed the clinical and pathologic details of their
      23-page, approximately 9-font article into two Tables, but have otherwise
      translated the complete text of this seminal paper. The journal cited above was
      first published in 1956 in Paris, France, and is currently published as Annales
      de Pathologie. Its editor is unaware of any prior English translation of this
      article.

PMID- 23153097
TI  - Growth-associated protein 43 expression in ganglionic and aganglionic colon.

PMID- 23153095
TI  - Proteome analysis of Cry4Ba toxin-interacting Aedes aegypti lipid rafts using
      geLC-MS/MS.
AB  - Lipid rafts are microdomains in the plasma membrane of eukaryotic cells. Among
      their many functions, lipid rafts are involved in cell toxicity caused by pore
      forming bacterial toxins including Bacillus thuringiensis (Bt) Cry toxins. We
      isolated lipid rafts from brush border membrane vesicles (BBMV) of Aedes aegypti
      larvae as a detergent resistant membrane (DRM) fraction on density gradients.
      Cholesterol, aminopeptidase (APN), alkaline phosphatase (ALP) and the raft marker
      flotillin were preferentially partitioned into the lipid raft fraction. When
      mosquitocidal Cry4Ba toxin was preincubated with BBMV, Cry4Ba localized to lipid
      rafts. A proteomic approach based on one-dimensional gel electrophoresis, in-gel
      trypsin digestion, followed by liquid chromatography-mass spectrometry (geLC
      MS/MS) identified a total of 386 proteins. Of which many are typical lipid raft
      marker proteins including flotillins and glycosylphosphatidylinositol (GPI)
      anchored proteins. Identified raft proteins were annotated in silico for
      functional and physicochemical characteristics. Parameters such as distribution
      of isoelectric point, molecular mass, and predicted post-translational
      modifications relevant to lipid raft proteins (GPI anchorage and myristoylation
      or palmitoylation) were analyzed for identified proteins in the DRM fraction.
      From a functional point of view, this study identified proteins implicated in Cry
      toxin interactions as well as membrane-associated proteins expressed in the
      mosquito midgut that have potential relevance to mosquito biology and vector
      management.

PMID- 23153098
TI  - Nitrogen origins and the role of ozonation in the formation of haloacetonitriles
      and halonitromethanes in chlorine water treatment.
AB  - Nitrogenous disinfection byproducts (N-DBPs) such as haloacetonitriles (HANs) and
      halonitromethanes (HNMs) are formed during water chlorination. Preozonation is
      sometimes applied to control trihalomethane (THM) formation, but this may risk
      promoting the formation of HNMs and HANs. The role of ozone in the formation of
      HANs and HNMs in natural waters remains unclear. The nitrogen sources involved in
      HAN and HNM formation during the chloramination of dissolved organic matter (DOM)
      with and without preozonation were evaluated using (15)N-labeled monochloramine.
      The origin of the nitrogen involved in HAN formation was found to depend on the
      ratio of dissolved organic carbon to nitrogen. In nitrogen-rich solutions HAN
      nitrogen was mainly from DOM constituents. The formation of (15)N-labeled
      dichloroacetontrile (DCAN) accounted for approximately 30% of the DCAN produced
      from all hydrophilic acidic and neutral isolates, which have low carbon to
      nitrogen ratios, while it reached over 50% for the hydrophobic acidic, basic, and
      neutral isolates with high carbon to nitrogen ratios. Unlabeled
      trichloronitromethane (TCNM) accounted for over 90% of the total TCNM produced
      from most of the isolates. The remaining less than 10% of the TCNM was probably
      generated through an aldehyde pathway. Preozonation reduced DCAN but enhanced the
      yield of TCNM. The destruction of amino acids and amine structures and subsequent
      formation of nitro groups by preozonation may help explain the reduced DCAN and
      increased TCNM formation.

PMID- 23153101
TI  - Psychological impact of Peyronie's disease: a review.
AB  - INTRODUCTION: Peyronie's disease (PD) is characterized by an accumulation of scar
      tissue in the tunica albuginea of the penis that causes curvature and deformity.
      PD can result in psychological distress, depression, or anxiety, which often goes
      untreated. AIMS: To review the current literature on the psychological impact of
      PD, educate healthcare providers about the psychological components of the
      disease, and propose interventions that address the psychological and sexual
      challenges patients and their partners may encounter. METHODS: We performed a
      MEDLINE search, limited to English, using the terms "Peyronie's disease" AND
      "psychological" OR "psychosocial," and select references were included for
      review. MAIN OUTCOME MEASURE: Critical review of the currently available English
      language literature. RESULTS: PD and its associated deformity often impairs
      sexual relations and frequently leads to psychological and psychosocial sequelae
      for affected individuals. Many men experience depression, low self-esteem, and
      emotional distress; these problems markedly diminish the quality of life for
      affected individuals. The literature suggests that as many as 81% of men report
      "emotional difficulties," 48% report clinically meaningful depression (26%
      moderate; 21% severe), and 54% report relationship problems due to PD. The
      challenges imposed by PD include alterations in sexual relationships,
      restrictions on intimacy, social isolation, and stigmatization, all of which are
      linked and reinforce each other. Physicians may be unaware of the psychological
      sequelae suffered by patients and their partners. CONCLUSIONS: Improved awareness
      and education about the psychological consequences and treatment options for PD
      are necessary among healthcare providers. To best help patients and optimize
      outcomes, a team-based approach is needed that includes psychosocial assessment
      and appropriate resource referrals for the patient and his sexual partner.

PMID- 23153099
TI  - Prevalence and risk factors of gastroesophageal reflux symptoms in a Chinese
      retiree cohort.
AB  - BACKGROUND: Data about prevalence of gastroesophageal reflux diseases (GERD) from
      Asian populations are still scarce. To provide additional data on prevalence of
      GERD and investigate its potential risk factors, we performed this cross
      sectional study in the Taizhou Retiree Cohort. METHODS: After physical
      examination, the participants were asked whether they suffered with heartburn or
      acid regurgitation in the last 12 months by trained interviewers, and if yes, the
      severity and frequency of the symptoms were recorded. Odds ratios (ORs) with 95%
      confidence intervals (CIs) for the associations of obesity and other risk factors
      with GERD were derived from logistic regression models. RESULTS: 8831 retirees
      completed the questionnaire and physical examination. In total 150 (1.7%)
      reported the symptoms occurring at least once per week within the last 12 months
      before the interview. Compared with subjects without GERD, having a history of
      diabetes mellitus (OR 2.2, 95% CI 1.4-3.5), hypertension (OR 1.4, 95% CI 1.0
      2.1), gastritis (OR 8.2, 95% CI 5.8-11.5), peptic ulcer (OR 3.3, 95% CI 1.8-6.1)
      and high triglyceride level (>=1.81mmol/L) (OR 2.0, 95% CI 1.2-3.4) were
      associated with a significantly increased risk of GERD. However, there was no
      significant association between body mass index, waist-to-hip ratio or waist
      alone, smoking, consumption of alcohol & tea, and the occurrence of reflux
      symptoms. CONCLUSIONS: Compared with Western populations, the prevalence of GERD
      in this Chinese retiree cohort is low. A history of diabetes mellitus,
      hypertension, gastritis, peptic ulcer or hypertriglyceridaemia increases GERD
      risk in this population.

PMID- 23153100
TI  - RNA-seq and microarray complement each other in transcriptome profiling.
AB  - BACKGROUND: RNA-seq and microarray are the two popular methods employed for
      genome-wide transcriptome profiling. Current comparison studies have shown that
      transcriptome quantified by these two methods correlated well. However, none of
      them have addressed if they complement each other, considering the strengths and
      the limitations inherent with them. The pivotal requirement to address this
      question is the knowledge of a well known data set. In this regard, HrpX regulome
      from pathogenic bacteria serves as an ideal choice as the target genes of HrpX
      transcription factor are well studied due to their central role in pathogenicity.
      RESULTS: We compared the performance of RNA-seq and microarray in their ability
      to detect known HrpX target genes by profiling the transcriptome from the wild
      type and the hrpX mutant strains of gamma-Proteobacterium Xanthomonas citri
      subsp. citri. Our comparative analysis indicated that gene expression levels
      quantified by RNA-seq and microarray well-correlated both at absolute as well as
      relative levels (Spearman correlation-coefficient, rs > 0.76). Further, the
      expression levels quantified by RNA-seq and microarray for the significantly
      differentially expressed genes (DEGs) also well-correlated with qRT-PCR based
      quantification (rs = 0.58 to 0.94). Finally, in addition to the 55 newly
      identified DEGs, 72% of the already known HrpX target genes were detected by both
      RNA-seq and microarray, while, the remaining 28% could only be detected by either
      one of the methods. CONCLUSIONS: This study has significantly advanced our
      understanding of the regulome of the critical transcriptional factor HrpX. RNA
      seq and microarray together provide a more comprehensive picture of HrpX regulome
      by uniquely identifying new DEGs. Our study demonstrated that RNA-seq and
      microarray complement each other in transcriptome profiling.

PMID- 23153102
TI  - Molecular characterization of long terminal repeat sequences from Brazilian human
      immunodeficiency virus type 1 isolates.
AB  - HIV-1 provirus activation is under control of the long terminal repeat (LTR)-5'
      viral promoter region, which presents remarkable genetic variation among HIV-1
      subtypes. It is possible that molecular features of the LTR contribute to the
      unusual profile of the subtype C epidemic in the Brazilian Southern region. To
      characterize the LTR of Brazilian HIV isolates, we analyzed sequences from 21
      infected individuals from Porto Alegre and Salvador cities. Sequences were
      compared with subtype B and C reference strains from different countries.
      Phylogenetic analysis showed that 17 (81%) samples were subtype B and four (19%)
      were subtype C. Common patterns of transcription factor binding sites (TFBS) in
      subtypes B and C sequences were confirmed and other potential TFBS specific for
      subtype C were found. Brazilian subtype C sequences contained an additional NF
      kappaB biding site, as previously described for the majority of subtype C
      isolates. The high level of LTR polymorphisms identified in this study might be
      important for viral fitness.

PMID- 23153103
TI  - Nonlinear nanomedecine: harmonic nanoparticles toward targeted diagnosis and
      therapy.
AB  - Harmonic nanoparticles were first introduced in 2006 as biomarkers for nonlinear
      imaging. This review provides a general explanation of the physical mechanism at
      the basis of this novel approach, highlighting its benefits and the
      complementarity to fluorescent/luminescent labels. A series of application
      examples from the very recent literature are reported, ranging from in vitro cell
      monitoring to the first proofs of in vivo imaging and rare event detection in
      physiological fluids.

PMID- 23153105
TI  - Comparison of thoracic and abdominal cavity volumes during abdominal CO2
      insufflation and abdominal wall lift.
AB  - OBJECTIVE: To compare thoracic and abdominal cavity volumes during abdominal CO2
      insufflation and abdominal wall lift (AWL) conditions. STUDY DESIGN: In vitro
      cadaveric study. ANIMALS: Mature medium-to-large breed fresh canine cadavers (n =
      6). METHODS: Each cadaver was imaged with computed tomography (CT) under
      baseline, abdominal CO2 insufflation, and AWL conditions. Measurements of
      thoracic and abdominal cavities were performed for each condition using image
      analyzing software. Resulting volumes for each cadaver were converted to percent
      change from baseline to normalize the data. The t-tests were used to compare
      percent changes of both thoracic and abdominal volumes. RESULTS: Thoracic volume
      significantly decreased from baseline during CO2 insufflation (P < .01). No
      significant difference in thoracic volume occurred with AWL when compared with
      baseline. Abdominal volume increased by 80% with CO2 insufflation (95% CI: 56.4
      107.0%) but only 25% with AWL (95% CI: 12.3-37.8%). CONCLUSIONS: Abdominal CO2
      insufflation results in decreased thoracic volume when compared with baseline.
      AWL preserved thoracic volume similar to baseline. Abdominal volumes achieved
      with abdominal CO2 insufflation are significantly greater than those attained
      with AWL.

PMID- 23153104
TI  - Sun protection and exposure behaviors among Hispanic adults in the United States:
      differences according to acculturation and among Hispanic subgroups.
AB  - BACKGROUND: Skin cancer prevention interventions that target the growing number
      of U.S. Hispanics are lacking. The current study examined the prevalence and
      correlates of sun protection and exposure behaviors (i.e., sunscreen use, shade
      seeking, use of sun protective clothing, and sunburns) among U.S. Hispanics with
      sun sensitive skin, with a focus on potential differences according to
      acculturation and Hispanic origin. METHODS: The sample consisted of 1676 Hispanic
      adults who reported having sun sensitive skin (i.e., they would experience a
      sunburn if they went out in the sun for one hour without protection after several
      months of not being in the sun). Participants completed survey questions as part
      of the nationally representative 2010 National Health Interview Survey. Analyses
      were conducted in August 2012. RESULTS: Greater acculturation was linked with
      both risky (i.e., not wearing sun protective clothing) and protective (i.e.,
      using sunscreen) sun-related practices and with an increased risk of sunburns.
      Sun protection and exposure behaviors also varied according to individuals'
      Hispanic origin, with for example individuals of Mexican heritage having a higher
      rate of using sun protective clothing and experiencing sunburns than several
      other subgroups. CONCLUSIONS: Several Hispanic subpopulations (e.g., those who
      are more acculturated or from certain origins) represent important groups to
      target in skin cancer prevention interventions. Future research is needed to test
      culturally relevant, tailored interventions to promote sun protection behaviors
      among U.S. Hispanics. Such initiatives should focus on public health education
      and increasing healthcare provider awareness of the importance of skin cancer
      prevention among Hispanics.

PMID- 23153106
TI  - Patient-maintained propofol sedation using reaction time monitoring: a volunteer
      safety study.
AB  - Previous volunteer studies of an effect-site controlled, patient-maintained
      sedation system using propofol have demonstrated a risk of over-sedation. We have
      incorporated a reaction-time monitor into the handset of the patient-maintained
      sedation system to add an individualised patient-feedback mechanism. This study
      assessed if such reaction-time feedback modification would reduce the risk of
      over-sedation in 20 healthy volunteers deliberately attempting to over-administer
      themselves propofol. All the volunteers successfully sedated themselves without
      reaching any unsafe endpoints. All volunteers maintained verbal contact
      throughout, in accordance with the definition of conscious sedation. The mean
      (SD) lowest S(p) O(2)  was 97 (1.7) % when breathing room air and no volunteer
      required supplementary oxygen. The mean (SD) maximum effect-site propofol
      concentration reached was 1.7 (0.4) MUg.ml(-1) . The present system was found to
      be safer than its predecessors, allowing conscious sedation, but preventing over
      sedation.

PMID- 23153107
TI  - Photoionization cross sections and asymmetry parameters for the valence shell of
      methanol.
AB  - Theoretical cross sections for photoionization of the methanol valence orbitals
      in covering a region up to 80 eV beyond the first ionization potential are
      reported. The molecular quantum defect orbital, MQDO, method, which has proved to
      be reliable in previous applications to molecular photoionization, has been used.
      To our knowledge, predictions of electronic partial cross section profiles on
      this molecule are made here for the first time, and we are not aware of any
      reported experimental data. Partial cross sections for production of parent and
      fragment ions of methanol have also been calculated and compared with previous
      measurements. In addition, the MQDO method has been used to calculate the angular
      distribution of photoelectrons for the valence orbitals of methanol over the 11
      50 eV photon energy range. Our results are compared with experimental data,
      showing a good agreement in most cases. We hope that the present results might be
      of use in atmospheric and interstellar chemistry, where this molecule plays an
      important role.

PMID- 23153109
TI  - Technetium chemistry in the fuel cycle: combining basic and applied studies.
AB  - Technetium is intimately linked with nuclear reactions. The ultraminute natural
      levels in the environment are due to the spontaneous fission of uranium isotopes.
      The discovery of technetium was born from accelerator reactions, and its use and
      presence in the modern world are directly due to nuclear reactors. While
      occupying a central location in the periodic table, the chemistry of technetium
      is poorly explored, especially when compared to its neighboring elements, i.e.,
      molybdenum, ruthenium, and rhenium. This state of affairs, which is tied to the
      small number of laboratories equipped to work with the long-lived (99)Tc isotope,
      provides a remarkable opportunity to combine basic studies with applications for
      the nuclear fuel cycle. An example is given through examination of the technetium
      halide compounds. Binary metal halides represent some of the most fundamental of
      inorganic compounds. The synthesis of new technetium halides demonstrates trends
      with structure, coordination number, and speciation that can be utilized in the
      nuclear fuel cycle. Examples are provided for technetium-zirconium alloys as
      waste forms and the formation of reduced technetium species in separations.

PMID- 23153108
TI  - Impact of ADMA, endothelial progenitor cells and traditional cardiovascular risk
      factors on pulse wave velocity among prediabetic individuals.
AB  - BACKGROUND: Central arterial stiffness represents a well-established predictor of
      cardiovascular disease. Decreased circulating endothelial progenitor cells
      (EPCs), increased asymmetric dimethyl-arginine (ADMA) levels, traditional
      cardiovascular risk factors and insulin resistance have all been associated with
      increased arterial stiffness. The correlations of novel and traditional
      cardiovascular risk factors with central arterial stiffness in prediabetic
      individuals were investigated in the present study. METHODS: The study population
      consisted of 53 prediabetic individuals. Individuals were divided into groups of
      isolated impaired fasting glucose (IFG), isolated impaired glucose tolerance
      (IGT) and combined IGT-IFG. Age, sex, family history of diabetes, smoking
      history, body mass index (BMI), waist to hip ratio (WHR), waist circumference
      (WC), blood pressure, lipid profile, levels of high sensitive C-reactive protein
      (hsCRP), glomerular filtration rate (GFR), and history of antihypertensive or
      statin therapy were obtained from all participants. Insulin resistance was
      evaluated using the Homeostatic Model Assessment (HOMA-IR). Carotid -femoral
      pulse wave velocity was used as an index of arterial stiffness. Circulating EPC
      count and ADMA serum levels were also determined. RESULTS: Among studied
      individuals 30 (56.6%) subjects were diagnosed with isolated IFG, 9 (17%) with
      isolated IGT (17%) and 14 with combined IFG-IGT (26.4%). In univariate analysis
      age, mean blood pressure, fasting glucose, total cholesterol, LDL cholesterol,
      and ADMA levels positively correlated with pulse-wave velocity while exercise and
      GFR correlated negatively. EPC count did not correlate with PWV. In multivariate
      stepwise regression analysis PWV correlated independently and positively with LDL
      Cholesterol (low density lipoprotein) and ADMA levels and negatively with
      exercise. CONCLUSIONS: Elevated ADMA and LDL-C levels are strongly associated
      with increased arterial stiffness among pre-diabetic subjects. In contrast
      exercise inversely correlated with arterial stiffness.

PMID- 23153110
TI  - The effects of six weeks of supplementation with multi-ingredient performance
      supplements and resistance training on anabolic hormones, body composition,
      strength, and power in resistance-trained men.
AB  - BACKGROUND: Resistance training (RT) enhances muscle protein synthesis and
      hypertrophy while increasing strength and power. Some multi-ingredient
      performance supplements (MIPS) have been shown to augment the physiological
      improvements associated with RT. The purpose of this study was to investigate the
      impact of specific pre- and post-workout MIPS on anabolic hormones, body
      composition, muscle strength, and power in resistance-trained men participating
      in a periodized RT program. METHODS: Twenty-four ( mean +/- SE; 24.0 +/- 0.9
      years; 180.5 +/- 5.8 cm; 83.7 +/- 0.5 kg) resistance-trained men completed 6 wks
      of periodized RT (3x/wk). Participants were assigned to one of two groups based
      upon maximal voluntary contraction of the quadriceps (Biodex) to lean mass (LM)
      ratio. Group 1 (n = 13; MIPS) consumed one serving of NO-Shotgun(r) (whey
      protein, casein protein, branched-chain amino acids, creatine, beta alanine, and
      caffeine) before each workout and one serving of NO-Synthesize(r) (whey protein,
      casein protein, branched-chain amino acids, creatine, and beta alanine; Vital
      Pharmaceuticals, Inc., Davie, FL) immediately after each workout and on non-RT
      days. Group 2 (n = 11; Placebo; PLA) consumed a flavor-matched isocaloric
      maltodextrin placebo. Serum insulin-like growth factor 1, human growth hormone,
      testosterone, body composition (DXA), circumferences, 1-repetition maximal
      strength (1RM) of the upper (chest press) and lower body (leg press), and
      anaerobic power (Wingate test) were assessed before and after the intervention.
      Statistical analysis included a 2 * 2 (group x time) ANOVA with repeated
      measures. Tukey LSD post hoc tests were used to examine pairwise differences.
      Significance was set at p < 0.05. RESULTS: There was a main time effect (p =
      0.035) for testosterone to increase, but no differences between groups were
      observed. There were no differences in the other blood hormones. Group x time
      interactions were observed for LM (MIPS: PRE, 62.9 +/- 2.1 to POST, 65.7 +/- 2.0
      vs. PLA: PRE, 63.5 +/- 2.3 to POST, 64.8 +/- 2.5 kg; p = 0.017). Only a main
      effect of time was noted for circumference measures. Both groups increased upper
      and lower body 1RM strength to a similar degree. MIPS significantly increased
      peak anaerobic power (PRE, 932.7 +/- 172.5 W vs. POST, 1119.2 +/- 183.8 W, p =
      0.002) while PLA remained unchanged (PRE, 974.4 +/- 44.1 W vs. POST, 1033.7 +/-
      48.6 W, p = 0.166). CONCLUSION: Consumption of MIPS during the course of a
      periodized RT program facilitated training-induced improvement in LM in trained
      males, whereas the consumption of PLA did not. MIPS improved measures of
      anaerobic power while PLA did not.

PMID- 23153111
TI  - [5 + 2] cycloaddition reactions in organic and natural product synthesis.

PMID- 23153112
TI  - Effect of initial ion positions on the interactions of monovalent and divalent
      ions with a DNA duplex as revealed with atomistic molecular dynamics simulations.
AB  - Monovalent (Na(+)) and divalent (Mg(2+)) ion distributions around the Dickerson
      Drew dodecamer were studied by atomistic molecular dynamics (MD) simulations with
      AMBER molecular modeling software. Different initial placements of ions were
      tried and the resulting effects on the ion distributions around DNA were
      investigated. For monovalent ions, results were found to be nearly independent of
      initial cation coordinates. However, Mg(2+) ions demonstrated a strong initial
      coordinate dependent behavior. While some divalent ions initially placed near the
      DNA formed essentially permanent direct coordination complexes with
      electronegative DNA atoms, Mg(2+) ions initially placed further away from the
      duplex formed a full, nonexchanging, octahedral first solvation shell. These
      fully solvated cations were still capable of binding with DNA with events lasting
      up to 20 ns, and in comparison were bound much longer than Na(+) ions. Force
      field parameters were also investigated with modest and little differences
      arising from ion (ions94 and ions08) and nucleic acid description (ff99,
      ff99bsc0, and ff10), respectively. Based on known Mg(2+) ion solvation structure,
      we conclude that in most cases Mg(2+) ions retain their first solvation shell,
      making only solvent-mediated contacts with DNA duplex. The proper way to simulate
      Mg(2+) ions around DNA duplex, therefore, should begin with ions placed in the
      bulk water. 

PMID- 23153113
TI  - Fe3O4 magnetic nanoparticle peroxidase mimetic-based colorimetric assay for the
      rapid detection of organophosphorus pesticide and nerve agent.
AB  - Rapid and sensitive detection methods are in urgent demand for the screening of
      extensively used organophosphorus pesticides and highly toxic nerve agents for
      their neurotoxicity. In this study, we developed a novel Fe(3)O(4) magnetic
      nanoparticle (MNP) peroxidase mimetic-based colorimetric method for the rapid
      detection of organophosphorus pesticides and nerve agents. The detection assay is
      composed of MNPs, acetylcholinesterase (AChE), and choline oxidase (CHO). The
      enzymes AChE and CHO catalyze the formation of H(2)O(2) in the presence of
      acetylcholine, which then activates MNPs to catalyze the oxidation of
      colorimetric substrates to produce a color reaction. After incubation with the
      organophosphorus neurotoxins, the enzymatic activity of AChE was inhibited and
      produced less H(2)O(2), resulting in a decreased catalytic oxidation of
      colorimetric substrates over MNP peroxidase mimetics, accompanied by a drop in
      color intensity. Three organophosphorus compounds were tested on the assay:
      acephate and methyl-paraoxon as representative organophosphorus pesticides and
      the nerve agent Sarin. The novel assay displayed substantial color change after
      incubation in organophosphorus neurotoxins in a concentration-dependent manner.
      As low as 1 nM Sarin, 10 nM methyl-paraoxon, and 5 MUM acephate are easily
      detected by the novel assay. In conclusion, by employing the peroxidase-mimicking
      activity of MNPs, the developed colorimetric assay has the potential of becoming
      a screening tool for the rapid and sensitive assessment of the neurotoxicity of
      an overwhelming number of organophosphate compounds.

PMID- 23153114
TI  - Recent advances in ocular drug delivery.
AB  - Amongst the various routes of drug delivery, the field of ocular drug delivery is
      one of the most interesting and challenging endeavors facing the pharmaceutical
      scientist. Recent research has focused on the characteristic advantages and
      limitations of the various drug delivery systems, and further research will be
      required before the ideal system can be developed. Administration of drugs to the
      ocular region with conventional delivery systems leads to short contact time of
      the formulations on the epithelium and fast elimination of drugs. This transient
      residence time involves poor bioavailability of drugs which can be explained by
      the tear production, non-productive absorption and impermeability of corneal
      epithelium. Anatomy of the eye is shortly presented and is connected with
      ophthalmic delivery and bioavailability of drugs. In the present update on ocular
      dosage forms, chemical delivery systems such as prodrugs, the use of
      cyclodextrins to increase solubility of various drugs, the concept of penetration
      enhancers and other ocular drug delivery systems such as polymeric gels,
      bioadhesive hydrogels, in-situ forming gels with temperature-, pH-, or
      osmotically induced gelation, combination of polymers and colloidal systems such
      as liposomes, niosomes, cubosomes, microemulsions, nanoemulsions and
      nanoparticles are discussed. Novel ophthalmic delivery systems propose the use of
      many excipients to increase the viscosity or the bioadhesion of the product. New
      formulations like gels or colloidal systems have been tested with numerous active
      substances by in vitro and in vivo studies. Sustained drug release and increase
      in drug bioavailability have been obtained, offering the promise of innovation in
      drug delivery systems for ocular administration. Combining different properties
      of pharmaceutical formulations appears to offer a genuine synergy in
      bioavailability and sustained release. Promising results are obtained with
      colloidal systems which present very comfortable conditions of use and prolonged
      action. 

PMID- 23153116
TI  - Unipept: tryptic peptide-based biodiversity analysis of metaproteome samples.
AB  - The Unipept web application (http://unipept.ugent.be) supports biodiversity
      analysis of large and complex metaproteome samples using tryptic peptide
      information obtained from shotgun MS/MS experiments. Its underlying index
      structure is designed to quickly retrieve all occurrences of a tryptic peptide in
      UniProtKB records. Taxon-specificity of the tryptic peptide is successively
      derived from these occurrences using a novel lowest common ancestor approach that
      is robust against taxonomic misarrangements, misidentifications, and
      inaccuracies. Not taking into account this identification noise would otherwise
      result in drastic loss of information. Dynamic treemaps visualize the
      biodiversity of metaproteome samples, which eases the exploration of samples with
      highly complex compositions. The potential of Unipept to gain novel insights into
      the biodiversity of a sample is evaluated by reanalyzing publicly available
      metaproteome data sets taken from the bacterial phyllosphere and the human gut.

PMID- 23153115
TI  - Interaction of dopamine transporter gene and observed parenting behaviors on
      attention-deficit/hyperactivity disorder: a structural equation modeling
      approach.
AB  - Emerging evidence suggests that some individuals may be simultaneously more
      responsive to the effects from environmental adversity and enrichment (i.e.,
      differential susceptibility). Given that parenting behavior and a variable number
      tandem repeat polymorphism in the 3'untranslated region of the dopamine
      transporter (DAT1) gene are each independently associated with attention
      deficit/hyperactivity disorder (ADHD), our goal was to evaluate the potential
      interactive effects of child DAT1 genotype with positive and negative parenting
      behaviors on childhood ADHD. We recruited an ethnically diverse sample of 150 six
      to nine-year-old boys and girls with and without ADHD. Children were genotyped
      for a common polymorphism of the DAT1 gene, and objective counts of observed
      parenting behavior (i.e., negativity and praise) were obtained from a valid
      parent-child interaction task. Structural equation modeling was used to examine
      the interactive effects of DAT1 and observed parenting with a latent ADHD factor.
      We detected a significant interaction between observed praise and child DAT1
      (coded additively), which suggested that praise was associated with increased
      ADHD, but only among youth with the 9/10 genotype. In addition, a marginally
      significant interaction between DAT1 (coded additively and recessively) and
      observed negativity emerged for ADHD, such that negativity was positively
      associated with ADHD but only for youth with the 9/9 genotype. Although
      differential susceptibility theory was not fully supported, these preliminary
      results suggest that interactive exchanges between parenting behavior and child
      genotype potentially contribute to the development of ADHD. Clinical implications
      for interactions between parenting behavior and child genotype are discussed.

PMID- 23153117
TI  - The versatile landscape of haematopoiesis: are leukaemia stem cells as versatile?
AB  - Since the early 1980s, developing haematopoietic cells have been categorised into
      three well-defined compartments: multi-potent haematopoietic stem cells (HSC),
      which are able to self-renew, followed by haematopoietic progenitor cells (HPC),
      which undergo decision-making and age as they divide rather than self-renew, and
      the final compartment of functional blood and immune cells. The classic model of
      haematopoiesis divides cells into two families, myeloid and lymphoid, and
      dictates a route to a particular cell fate. New discoveries question these long
      held principles, including: (i) the identification of lineage-biased cells that
      self-renew; (ii) a strict myeloid/lymphoid dichotomy is refuted by the existence
      of progenitors with lymphoid potential and an incomplete set of myeloid
      potentials; (iii) there are multiple routes to some end cell types; and (iv)
      thymocyte progenitor cells that have progressed some way along this pathway
      retain clandestine myeloid options. In essence, the progeny of HSC are more
      versatile and the process of haematopoiesis is more flexible than previously
      thought. Here we examine this new way of viewing haematopoiesis and the impact of
      rewriting an account of haematopoiesis on our understanding of what goes awry in
      leukaemia.

PMID- 23153118
TI  - Enhanced photovoltaic properties of Nb2O5-coated TiO2 3D ordered porous
      electrodes in dye-sensitized solar cells.
AB  - This paper describes the use of Nb2O5-coated TiO2 3D ordered porous electrodes in
      dye-sensitized solar cells. We employed bilayer inverse opal structures as a
      backbone of 3D porous structures, and the number of Nb2O5 coatings was
      controlled, determining the concentration of Nb2O5 coating. XPS measurements
      confirmed the formation of Nb2O5. The uniformity of the Nb2O5 coating was
      characterized by elemental mapping using SEM and TEM measurements. Photovoltaic
      measurement on dye-sensitized solar cells (DSSCs) that incorporated Nb2O5/TiO2
      inverse opal electrodes yielded a maximum efficiency of 7.23% for a 3.3 wt %
      Nb2O5 coating on a TiO2 IO structure. The Nb2O5 significantly increased the short
      circuit current density (J(SC)). Electrochemical impedance spectroscopy was used
      to measure the J(SC), revealing an enhanced electron injection upon deposition of
      the Nb2O5 coating.

PMID- 23153119
TI  - Semi-artificial mouse skin membrane feeding technique for adult tick,
      Haemaphysalis longicornis.
AB  - BACKGROUND: An in vitro artificial feeding technique for hard ticks is quite
      useful for studying the tick-pathogen interactions. Here, we report a novel semi
      artificial feeding technique for the adult parthenogenetic tick, Haemaphysalis
      longicornis, using mouse skin membrane. FINDINGS: Skin with attached adult ticks
      was removed from the mouse body at 4 to 5 days post-infestation for the
      construction of the feeding system. This system supplied with rabbit blood was
      kept in >95% relative humidity at 30 degrees C during the feeding, and ticks were
      fully engorged (artificially engorged, AE) within 12 to 48 h. For comparison,
      ticks were fed to engorgement solely on rabbit or mouse for 5 days as controls
      (naturally engorged on rabbit, NEr, or mouse, NEm). Blood digestion-related gene
      expression in the midgut and reproductive fitness were compared. Body weight, egg
      mass weight, egg conversion ratio, and hatchability of eggs did not show any
      significant differences. We analyzed transcription profiles of selected genes
      assayed by quantitative RT-PCR and revealed similar patterns of expression
      between NEr and AE but some differences between NEm and AE or NEm and NEr.
      CONCLUSIONS: Our results demonstrate that this semi-artificial feeding technique
      mimics natural feeding processes of ticks and can be utilized as a standardized
      method to inoculate pathogens, especially Babesia protozoa, into H. longicornis
      and possibly other tick species as well.

PMID- 23153120
TI  - Infectious sacroiliitis: a retrospective, multicentre study of 39 adults.
AB  - BACKGROUND: Non-brucellar and non-tuberculous infectious sacroiliitis (ISI) is a
      rare disease, with misleading clinical signs that delay diagnosis. Most
      observations are based on isolated case reports or small case series. Our aim was
      to describe the clinical, bacteriological, and radiological characteristics of
      ISI, as well as the evolution of these arthritis cases under treatment. METHODS:
      This retrospective study included all ISI cases diagnosed between 1995 and 2011
      in eight French rheumatology departments. ISI was diagnosed if sacroiliitis was
      confirmed bacteriologically or, in the absence of pathogenic agents, if clinical,
      biological, and radiological data was compatible with this diagnosis and
      evolution was favourable under antibiotic therapy. RESULTS: Overall, 39 cases of
      ISI were identified in adults, comprising 23 women and 16 men, with a mean age at
      diagnosis of 39.7 +/- 18.1 years. The left sacroiliac joint (SI) was affected in
      59% of cases, with five cases occurring during the post-partum period.
      Lumbogluteal pain was the most common symptom (36/39). Manipulations of the SI
      joint were performed in seven patients and were always painful. Mean score for
      pain using the visual analogue score was 7.3/10 at admission, while 16 patients
      were febrile at diagnosis. No risk factor was found for 30.7% of patients. A
      diagnosis of ISI was only suspected in five cases at admission. The mean time to
      diagnosis was long, being 43.3 +/- 69.1 days on average. Mean C-reactive protein
      was 149.7 +/- 115.3 mg/l, and leukocytosis (leukocytes >= 10 G/l) was uncommon (n
      = 15) (mean level of leukocytes 10.4 +/- 3.5 G/l). Radiographs (n = 33) were
      abnormal in 20 cases, revealing lesions of SI, while an abdominopelvic computed
      tomography (CT) scan (n = 27) was abnormal in 21 cases, suggesting arthritis of
      the SI joints in 13 cases (48.1%) and a psoas abscess in eight. Bone scans (n =
      14) showed hyperfixation of the SI in 13 cases. Magnetic resonance imaging (MRI)
      (n = 27), when focused on the SI (n = 25), directed towards the diagnosis to ISI
      in 25 cases. Pathogenic agents were isolated in 33 cases (84.6%) by means of
      articular puncture (n = 16), blood culture (n = 14), cytobacteriological
      examination of urine (n = 2), or puncture of the psoas (n = 1).Gram-positive
      cocci were the mostly isolated common bacteria, with a predominance of
      staphylococci (n = 21). The most frequently isolated gram-negative bacillus was
      Pseudomonas aeruginosa (n = 3). Evolution was favourable in 37 out of 39 patients
      under prolonged antibiotic therapy (mean duration 3.01 +/- 1.21 months).
      CONCLUSION: Our series confirmed that the clinical manifestations of ISI usually
      lead to delayed diagnosis. Based on our results, we suggest performing an MRI of
      the spine and SI in clinical situations characterised by lumbogluteal pain and
      symptoms of an infectious disease, such as fever.

PMID- 23153121
TI  - A histone arginine methylation localizes to nucleosomes in satellite II and III
      DNA sequences in the human genome.
AB  - BACKGROUND: Applying supervised learning/classification techniques to epigenomic
      data may reveal properties that differentiate histone modifications. Previous
      analyses sought to classify nucleosomes containing histone H2A/H4 arginine 3
      symmetric dimethylation (H2A/H4R3me2s) or H2A.Z using human CD4+ T-cell chromatin
      immunoprecipitation sequencing (ChIP-Seq) data. However, these efforts only
      achieved modest accuracy with limited biological interpretation. Here, we
      investigate the impact of using appropriate data pre-processing -deduplication,
      normalization, and position- (peak-) finding to identify stable nucleosome
      positions - in conjunction with advanced classification algorithms, notably
      discriminatory motif feature selection and random forests. Performance
      assessments are based on accuracy and interpretative yield. RESULTS: We achieved
      dramatically improved accuracy using histone modification features (99.0%;
      previous attempts, 68.3%) and DNA sequence features (94.1%; previous attempts,
      <60%). Furthermore, the algorithms elicited interpretable features that withstand
      permutation testing, including: the histone modifications H4K20me3 and H3K9me3,
      which are components of heterochromatin; and the motif TCCATT, which is part of
      the consensus sequence of satellite II and III DNA. Downstream analysis
      demonstrates that satellite II and III DNA in the human genome is occupied by
      stable nucleosomes containing H2A/H4R3me2s, H4K20me3, and/or H3K9me3, but not 18
      other histone methylations. These results are consistent with the recent
      biochemical finding that H4R3me2s provides a binding site for the DNA
      methyltransferase (Dnmt3a) that methylates satellite II and III DNA. CONCLUSIONS:
      Classification algorithms applied to appropriately pre-processed ChIP-Seq data
      can accurately discriminate between histone modifications. Algorithms that
      facilitate interpretation, such as discriminatory motif feature selection, have
      the added potential to impart information about underlying biological mechanism.

PMID- 23153122
TI  - Assessing California groundwater susceptibility using trace concentrations of
      halogenated volatile organic compounds.
AB  - Twenty-four halogenated volatile organic compounds (hVOCs) and SF6 were measured
      in groundwater samples collected from 312 wells across California at
      concentrations as low as 10-12 grams per kilogram groundwater. The hVOCs detected
      are predominately anthropogenic (i.e., "ahVOCs") and as such their distribution
      delineates where groundwaters are impacted and susceptible to human activity.
      ahVOC detections were broadly consistent with air-saturated water concentrations
      in equilibrium with a combination of industrial-era global and regional hVOC
      atmospheric abundances. However, detection of ahVOCs in nearly all of the samples
      collected, including ancient groundwaters, suggests the presence of a sampling or
      analytical artifact that confounds interpretation of the very-low concentration
      ahVOC data. To increase our confidence in ahVOC detections we establish screening
      levels based on ahVOC concentrations in deep wells drawing ancient groundwater in
      Owens Valley. Concentrations of ahVOCs below the Owens Valley screening levels
      account for a large number of the detections in prenuclear groundwater across
      California without significant loss of ahVOC detections in shallow, recently
      recharged groundwaters. Over 80% of the groundwaters in this study contain at
      least one ahVOC after screening, indicating that the footprint of human industry
      is nearly ubiquitous and that most California groundwaters are vulnerable to
      contamination from land-surface activities.

PMID- 23153123
TI  - The use of photodynamic therapy in the treatment of lentigo maligna.

PMID- 23153124
TI  - Influence of community social norms on spousal violence: a population-based
      multilevel study of Nigerian women.
AB  - OBJECTIVES: We examined whether social norms toward spousal violence in Nigeria,
      at the state level, are associated with a woman's exposure to physical and sexual
      violence perpetrated by her husband. METHODS: Using data from the 2008
      Demographic and Health Survey, we fit four 3-level random intercepts models to
      examine contextual factors associated with spousal violence while accounting for
      individual-level predictors. RESULTS: Of the 18,798 ever-married Nigerian women
      in our sample, 18.7% reported exposure to spousal sexual or physical violence.
      The prevalence was geographically patterned by state and ranged from 3% to 50%.
      Permissive state-level social norms toward spousal violence were positively
      associated with a woman's report of physical and sexual violence perpetrated by
      her husband (odds ratio [OR] = 1.80; 95% confidence interval [CI] = 1.17, 2.77),
      after adjusting for individual-level characteristics. A number of individual
      level variables were significantly associated with victimization, including a
      woman's accepting beliefs toward spousal violence (OR = 1.11; 95% CI = 1.09,
      1.14). Women living in states with Sharia law were less likely to report spousal
      violence (OR = 0.58; 95% CI = 0.35, 0.95). CONCLUSIONS: Efforts to end violence
      against women, particularly spousal violence, should consider broader social and
      contextual determinants of violence including social norms.

PMID- 23153125
TI  - Unhealthy interactions: the role of stereotype threat in health disparities.
AB  - Stereotype threat is the unpleasant psychological experience of confronting
      negative stereotypes about race, ethnicity, gender, sexual orientation, or social
      status.  Hundreds of published studies show how the experience of stereotype
      threat can impair intellectual functioning and interfere with test and school
      performance. Numerous published interventions derived from this research have
      improved the performance and motivation of individuals targeted by low-ability
      stereotypes.  Stereotype threat theory and research provide a useful lens for
      understanding and reducing the negative health consequences of interracial
      interactions for African Americans and members of similarly stigmatized minority
      groups. Here we summarize the educational outcomes of stereotype threat and
      examine the implications of stereotype threat for health and health-related
      behaviors.

PMID- 23153126
TI  - History, biology, and health inequities: emergent embodied phenotypes and the
      illustrative case of the breast cancer estrogen receptor.
AB  - How we think about biology--in historical, ecological, and societal context-
      matters for framing causes of and solutions to health inequities. Drawing on new
      insights from ecological evolutionary developmental biology and ecosocial theory,
      I question dominant gene-centric and ultimately static approaches to
      conceptualizing biology, using the example of the breast cancer estrogen receptor
      (ER). Analyzed in terms of its 4 histories--societal, individual (life course),
      tumor (cellular pathology), and evolutionary--the ER is revealed as a flexible
      characteristic of cells, tumors, individuals, and populations, with magnitudes of
      health inequities tellingly changing over time. This example suggests our science
      will likely be better served by conceptualizing disease and its biomarkers, along
      with changing magnitudes of health inequities, as embodied history--that is,
      emergent embodied phenotype, not innate biology.

PMID- 23153127
TI  - Suicide, guns, and public policy.
AB  - Suicide is a serious public health concern that is responsible for almost 1
      million deaths each year worldwide. It is commonly an impulsive act by a
      vulnerable individual. The impulsivity of suicide provides opportunities to
      reduce the risk of suicide by restricting access to lethal means.  In the United
      States, firearms, particularly handguns, are the most common means of suicide.
      Despite strong empirical evidence that restriction of access to firearms reduces
      suicides, access to firearms in the United States is generally subject to few
      restrictions.  Implementation and evaluation of measures such as waiting periods
      and permit requirements that restrict access to handguns should be a top priority
      for reducing deaths from impulsive suicide in the United States.

PMID- 23153128
TI  - Beautifully toxic: the effects of a Burmese cosmetic practice.

PMID- 23153129
TI  - Efficacy of frequent monitoring with swift, certain, and modest sanctions for
      violations: insights from South Dakota's 24/7 Sobriety Project.
AB  - OBJECTIVES: We examined the public health impact of South Dakota's 24/7 Sobriety
      Project, an innovative program requiring individuals arrested for or convicted of
      alcohol-involved offenses to submit to breathalyzer tests twice per day or wear a
      continuous alcohol monitoring bracelet. Those testing positive are subject to
      swift, certain, and modest sanctions. METHODS: We conducted differences-in
      differences analyses comparing changes in arrests for driving while under the
      influence of alcohol (DUI), arrests for domestic violence, and traffic crashes in
      counties to the program with counties without the program. RESULTS: Between 2005
      and 2010, more than 17,000 residents of South Dakota-including more than 10% of
      men aged 18 to 40 years in some counties-had participated in the 24/7 program. At
      the county level, we documented a 12% reduction in repeat DUI arrests (P = .023)
      and a 9% reduction in domestic violence arrests (P = .035) following adoption of
      the program. Evidence for traffic crashes was mixed. CONCLUSIONS: In community
      supervision settings, frequent alcohol testing with swift, certain, and modest
      sanctions for violations can reduce problem drinking and improve public health
      outcomes.

PMID- 23153130
TI  - Using science to improve communications about suicide among military and veteran
      populations: looking for a few good messages.
AB  - Concern about suicide in US military and veteran populations has prompted efforts
      to identify more effective prevention measures.  Recent expert panel reports have
      recommended public communications as one component of a comprehensive effort.
      Messaging about military and veteran suicide originates from many sources and
      often does not support suicide prevention goals or adhere to principles for
      developing effective communications.  There is an urgent need for strategic,
      science-based, consistent messaging guidance in this area. Although literature on
      the effectiveness of suicide prevention communications for these populations is
      lacking, this article summarizes key findings from several bodies of research
      that offer lessons for creating safe and effective messages that support and
      enhance military and veteran suicide prevention efforts.

PMID- 23153131
TI  - Multivariate or multivariable regression?
AB  - The terms multivariate and multivariable are often used interchangeably in the
      public health literature. However, these terms actually represent 2 very distinct
      types of analyses. We define the 2 types of analysis and assess the prevalence of
      use of the statistical term multivariate in a 1-year span of articles published
      in the American Journal of Public Health. Our goal is to make a clear distinction
      and to identify the nuances that make these types of analyses so distinct from
      one another.

PMID- 23153132
TI  - Climate change and the role of food price in determining obesity risk.

PMID- 23153133
TI  - The right US men's health report: high time to adjust priorities and attack
      disparities.

PMID- 23153134
TI  - Victimization and suicidality among Dutch lesbian, gay, and bisexual youths.
AB  - We examined Netherlands Institute for Social Research data, collected between May
      and August 2009, on 274 Dutch lesbian, gay, and bisexual youths. The data showed
      that victimization at school was associated with suicidal ideation and actual
      suicide attempts. Homophobic rejection by parents was also associated with actual
      suicide attempts. Suicidality in this population could be reduced by supporting
      coping strategies of lesbian, gay, and bisexual youths who are confronted with
      stigmatization by peers and parents, and by schools actively promoting acceptance
      of same-sex sexuality.

PMID- 23153136
TI  - Effect of climate change and food insecurity on low-income households.

PMID- 23153137
TI  - Food insecurity and climate change.

PMID- 23153135
TI  - Fundamental causes of colorectal cancer mortality in the United States:
      understanding the importance of socioeconomic status in creating inequality in
      mortality.
AB  - OBJECTIVES: We used the fundamental cause hypothesis as a framework for
      understanding the creation of health disparities in colorectal cancer mortality
      in the United States from 1968 to 2005. METHODS: We used negative binomial
      regression to analyze trends in county-level gender-, race-, and age-adjusted
      colorectal cancer mortality rates among individuals aged 35 years or older.
      RESULTS: Prior to 1980, there was a stable gradient in colorectal cancer
      mortality, with people living in counties of higher socioeconomic status (SES)
      being at greater risk than people living in lower SES counties. Beginning in
      1980, this gradient began to narrow and then reversed as people living in higher
      SES counties experienced greater reductions in colorectal cancer mortality than
      those in lower SES counties. CONCLUSIONS: Our findings support the fundamental
      cause hypothesis: once knowledge about prevention and treatment of colorectal
      cancer became available, social and economic resources became increasingly
      important in influencing mortality rates.

PMID- 23153139
TI  - When concealed handgun licensees break bad: criminal convictions of concealed
      handgun licensees in Texas, 2001-2009.
AB  - OBJECTIVES: We explored differences in criminal convictions between holders and
      nonholders of a concealed handgun license (CHL) in Texas. METHODS: The Texas
      Department of Public Safety (DPS) provides annual data on criminal convictions of
      holders and nonholders of CHLs. We used 2001 to 2009 DPS data to investigate the
      differences in the distribution of convictions for these 2 groups across 9 types
      of criminal offenses. We calculated z scores for the differences in the types of
      crimes for which CHL holders and nonholders were convicted. RESULTS: CHL holders
      were much less likely than nonlicensees to be convicted of crimes. Most nonholder
      convictions involved higher-prevalence crimes (burglary, robbery, or simple
      assault). CHL holders' convictions were more likely to involve lower-prevalence
      crimes, such as sexual offenses, gun offenses, or offenses involving a death.
      CONCLUSIONS: Our results imply that expanding the settings in which concealed
      carry is permitted may increase the risk of specific types of crimes, some quite
      serious in those settings. These increased risks may be relatively small.
      Nonetheless, policymakers should consider these risks when contemplating reducing
      the scope of gun-free zones.

PMID- 23153140
TI  - Association between community socioeconomic position and HIV diagnosis rate among
      adults and adolescents in the United States, 2005 to 2009.
AB  - OBJECTIVES: We examined the association between socioeconomic position (SEP) and
      HIV diagnosis rates in the United States and whether racial/ethnic disparities in
      diagnosis rates persist after control for SEP. METHODS: We used cases of HIV
      infection among persons aged 13 years and older, diagnosed 2005 through 2009 in
      37 states and reported to national HIV surveillance through June 2010, and US
      Census data, to examine associations between county-level SEP measures and 5-year
      average annual HIV diagnosis rates overall and among race/ethnicity-sex groups.
      RESULTS: The HIV diagnosis rate was significantly higher for individuals in the
      low-SEP tertile than for those in the high-SEP tertile (rate ratios for low- vs
      high-SEP tertiles range = 1.68-3.38) except for White males and Hispanic females.
      The SEP disparities were larger for minorities than for Whites. Racial
      disparities persisted after we controlled for SEP, urbanicity, and percentage of
      population aged 20 to 50 years, and were high in the low-SEP tertile for males
      and in low- and high-SEP tertiles for females. CONCLUSIONS: Findings support
      continued prioritization of HIV testing, prevention, and treatment to persons in
      economically deprived areas, and Blacks of all SEP levels.

PMID- 23153138
TI  - Sex, drugs (methamphetamines), and the Internet: increasing syphilis among men
      who have sex with men in California, 2004-2008.
AB  - OBJECTIVES: We examined primary and secondary syphilis cases among men who have
      sex with men (MSM) in California, and the association of methamphetamine use and
      Internet use to meet sex partners (Internet use) with number of sex partners.
      METHODS: We analyzed California surveillance data for MSM who were diagnosed with
      syphilis between 2004 and 2008, to assess differences in the mean number of sex
      partners by methamphetamine use and mutually exclusive groups of patients
      reporting Internet use (Internet users). RESULTS: Large proportions of patients
      reported methamphetamine use (19.2%) and Internet use (36.4%). From 2006 through
      2008, Adam4Adam was the most frequently reported Web site statewide, despite
      temporal and regional differences in Web site usage. Methamphetamine users
      reported more sex partners (mean = 11.7) than nonmethamphetamine users (mean =
      5.6; P < .001). Internet users reported more sex partners (mean = 9.8) than non
      Internet users (mean = 5.0; P < .001). Multivariable analysis of variance
      confirmed an independent association of methamphetamine and Internet use with
      increased numbers of sex partners. CONCLUSIONS: Higher numbers of partners among
      MSM syphilis patients were associated with methamphetamine and Internet use.
      Collaboration between currently stand-alone interventions targeting
      methamphetamine users and Internet users may offer potential advances in sexually
      transmitted disease control efforts.

PMID- 23153141
TI  - "Healthconomic crises": public health and neoliberal economic crises.

PMID- 23153142
TI  - Experiences of transgender-related discrimination and implications for health:
      results from the Virginia Transgender Health Initiative Study.
AB  - OBJECTIVES: We examined relationships between social determinants of health and
      experiences of transgender-related discrimination reported by transgender people
      in Virginia. METHODS: In 2005 through 2006, 387 self-identified transgender
      people completed a statewide health needs assessment; 350 who completed
      eligibility questions were included in this examination of factors associated
      with experiences of discrimination in health care, employment, or housing. We fit
      multivariate logistic regression models using generalized estimating equations to
      adjust for survey modality (online vs paper). RESULTS: Of participants, 41% (n =
      143) reported experiences of transgender-related discrimination. Factors
      associated with transgender-related discrimination were geographic context,
      gender (female-to male spectrum vs male-to-female spectrum), low socioeconomic
      status, being a racial/ethnic minority, not having health insurance, gender
      transition indicators (younger age at first transgender awareness), health care
      needed but unable to be obtained (hormone therapy and mental health services),
      history of violence (sexual and physical), substance use health behaviors
      (tobacco and alcohol), and interpersonal factors (family support and community
      connectedness). CONCLUSIONS: Findings suggest that transgender Virginians
      experience widespread discrimination in health care, employment, and housing.
      Multilevel interventions are needed for transgender populations, including legal
      protections and training for health care providers.

PMID- 23153144
TI  - The politicization of abortion and the evolution of abortion counseling.
AB  - The field of abortion counseling originated in the abortion rights movement of
      the 1970s. During its evolution to the present day, it has faced significant
      challenges, primarily arising from the increasing politicization and
      stigmatization of abortion since legalization. Abortion counseling has been
      affected not only by the imposition of antiabortion statutes, but also by the
      changing needs of patients who have come of age in a very different era than when
      this occupation was first developed. One major innovation--head and heart
      counseling--departs in significant ways from previous conventions of the field
      and illustrates the complex and changing political meanings of abortion and
      therefore the challenges to abortion providers in the years following Roe v Wade.

PMID- 23153143
TI  - Gender role conflict among African American men who have sex with men and women:
      associations with mental health and sexual risk and disclosure behaviors.
AB  - OBJECTIVES: We investigated whether high gender role conflict (GRC; internal
      conflict with traditional gender-role stereotypes and an individual's perceived
      need to comply with these roles) is associated with psychological distress and
      HIV-related risk behaviors in a sample of African American men who have sex with
      men and women (MSMW). METHODS: We analyzed baseline data collected from
      questionnaires completed by 400 MSMW participating in the Men of African American
      Legacy Empowering Self project in Los Angeles, California, in 2007 to 2010 for
      associations between participants' GRC and experiences of poor mental health and
      HIV risk outcomes. RESULTS: MSMW who reported higher levels of GRC than other
      participants also reported more psychological distress, lower self-esteem,
      greater internalized homophobia, less HIV knowledge, lower risk reduction skills,
      less disclosure of same-sex behaviors to others, and more unprotected vaginal or
      anal intercourse with female partners. CONCLUSIONS: Future research should
      consider how high GRC affects African American MSMW's lives and identify specific
      approaches to help alleviate the psychological distress and other negative
      behavioral outcomes associated with internal conflict caused by rigid gender role
      socialization.

PMID- 23153145
TI  - Predictors of active injection drug use in a cohort of patients infected with
      hepatitis C virus.
AB  - OBJECTIVES: We investigated potential risk factors for active injection drug use
      (IDU) in an inner-city cohort of patients infected with hepatitis C virus (HCV).
      METHODS: We used log-binomial regression to identify factors independently
      associated with active IDU during the first 3 years of follow-up for the 289
      participants who reported ever having injected drugs at baseline. RESULTS:
      Overall, 142 (49.1%) of the 289 participants reported active IDU at some point
      during the follow-up period. In a multivariate model, being unemployed
      (prevalence ratio [PR] = 1.93; 95% confidence interval [CI] = 1.24, 3.03) and
      hazardous alcohol drinking (PR = 1.67; 95% CI = 1.34, 2.08) were associated with
      active IDU. Smoking was associated with IDU but this association was not
      statistically significant. Patients with all 3 of those factors were 3 times as
      likely to report IDU during follow-up as those with 0 or 1 factor (PR = 3.3; 95%
      CI = 2.2, 4.9). Neither HIV coinfection nor history of psychiatric disease was
      independently associated with active IDU. CONCLUSIONS: Optimal treatment of
      persons with HCV infection will require attention to unemployment, alcohol use,
      and smoking in conjunction with IDU treatment and prevention.

PMID- 23153146
TI  - Felon disenfranchisement in the United States: a health equity perspective.
AB  - Approximately 13% of African American men are disqualified from voting because of
      a felony conviction. I used ecosocial theory to identify how institutionalized
      racism helps perpetuate health disparities and to explore pathways through which
      felon disenfranchisement laws may contribute to racial health disparities in the
      United States. From a literature review, I identified 2 potential pathways: (1)
      inability to alter inequitable public policies that differentially allocate
      resources for health; and (2) inability to reintegrate into society by voting,
      which contributes to allostatic load.

PMID- 23153147
TI  - Network mixing and network influences most linked to HIV infection and risk
      behavior in the HIV epidemic among black men who have sex with men.
AB  - OBJECTIVES: We evaluated network mixing and influences by network members upon
      Black men who have sex with men. METHODS: We conducted separate social and sexual
      network mixing analyses to determine the degree of mixing on risk behaviors
      (e.g., unprotected anal intercourse [UAI]). We used logistic regression to assess
      the association between a network "enabler" (would not disapprove of the
      respondent's behavior) and respondent behavior. RESULTS: Across the sample (n =
      1187) network mixing on risk behaviors was more assortative (like with like) in
      the sexual network (r(sex), 0.37-0.54) than in the social network (r(social),
      0.21-0.24). Minimal assortativity (heterogeneous mixing) among HIV-infected men
      on UAI was evident. Black men who have sex with men reporting a social network
      enabler were more likely to practice UAI (adjusted odds ratio = 4.06; 95%
      confidence interval = 1.64, 10.05) a finding not observed in the sexual network
      (adjusted odds ratio = 1.31; 95% confidence interval = 0.44, 3.91). CONCLUSIONS:
      Different mixing on risk behavior was evident with more disassortativity among
      social than sexual networks. Enabling effects of social network members may
      affect risky behavior. Attention to of high-risk populations' social networks is
      needed for effective and sustained HIV prevention.

PMID- 23153148
TI  - Individual and network factors associated with prevalent hepatitis C infection
      among rural Appalachian injection drug users.
AB  - OBJECTIVES: We determined the factors associated with hepatitis C (HCV) infection
      among rural Appalachian drug users. METHODS: This study included 394 injection
      drug users (IDUs) participating in a study of social networks and infectious
      disease risk in Appalachian Kentucky. Trained staff conducted HCV, HIV, and
      herpes simplex-2 virus (HSV-2) testing, and an interviewer-administered
      questionnaire measured self-reported risk behaviors and sociometric network
      characteristics. RESULTS: The prevalence of HCV infection was 54.6% among rural
      IDUs. Lifetime factors independently associated with HCV infection included HSV
      2, injecting for 5 or more years, posttraumatic stress disorder, injection of
      cocaine, and injection of prescription opioids. Recent (past-6-month) correlates
      of HCV infection included sharing of syringes (adjusted odds ratio = 2.24; 95%
      confidence interval = 1.32, 3.82) and greater levels of eigenvector centrality in
      the drug network. CONCLUSIONS: One factor emerged that was potentially unique to
      rural IDUs: the association between injection of prescription opioids and HCV
      infection. Therefore, preventing transition to injection, especially among
      prescription opioid users, may curb transmission, as will increased access to
      opioid maintenance treatment, novel treatments for cocaine dependence, and
      syringe exchange.

PMID- 23153149
TI  - Safer sex media messages and adolescent sexual behavior: 3-year follow-up results
      from project iMPPACS.
AB  - OBJECTIVES: We estimated the long-term (36-month) effects of Project iMPPACS, a
      multisite randomized controlled trial of mass media and small-group intervention
      for African American adolescents. METHODS: We collected 6 waves of longitudinal
      data on program participants aged 14 to 17 years (n = 1139) in Providence, Rhode
      Island; Syracuse, New York; Columbia, South Carolina; and Macon, Georgia, 36
      months (December 2009-December 2010) after the intervention began (August 2006
      January 2008). Seemingly unrelated regressions at each wave estimated the effects
      of 3 types of mass media messages (the thematic mediators: selection, pleasure,
      and negotiation) on condom use intention and self-reported unprotected vaginal
      sex events. RESULTS: All 3 mediators of behavior change that were introduced
      during the media intervention were sustained at the follow-up assessments at
      least 18 months after the intervention ended, with intention having the largest
      correlation. Unprotected vaginal sex increased with each wave of the study,
      although cities receiving media exposure had smaller increases. CONCLUSIONS:
      Project iMPPACS demonstrates that mass media influence delivered over an extended
      period, when adolescents were beginning to learn patterns of behavior associated
      with sex, persisted after the media program ended.

PMID- 23153150
TI  - Using the HIV surveillance system to monitor the National HIV/AIDS Strategy.
AB  - OBJECTIVES: To report on indicators of the National HIV/AIDS Strategy, we
      analyzed data collected through the national HIV surveillance system. METHODS: We
      analyzed data from adults and adolescents aged 13 years or older diagnosed with
      HIV in 13 US jurisdictions that have laboratory reporting of CD4+ T-lymphocyte
      (CD4) and viral load (VL) test results and enter CD4 and VL test results into the
      national surveillance system. RESULTS: Of 4899 people diagnosed in 2009, 81.7%
      had at least 1 CD4 or VL test performed within 3 months of diagnosis. A higher
      proportion of Whites (86.2%) than Blacks (78.4%) and Hispanics (82.6%) had a CD4
      or VL test. Of 53,642 people diagnosed through 2008 and living with HIV at the
      end of 2009 who had a VL test, 69.4% had a most recent VL of 200 copies per
      milliliter or less. The proportion of people with suppressed VLs differed among
      Blacks (60.2%), Hispanics (70.3%), and Whites (77.4%) and among people aged 13 to
      24 years (44.3%) compared with people aged 65 years or older (84.2%). Of men who
      have sex with men, 74.2% had a suppressed VL. CONCLUSIONS: The findings highlight
      disparities in access to and success of care.

PMID- 23153151
TI  - Hepatitis C testing, infection, and linkage to care among racial and ethnic
      minorities in the United States, 2009-2010.
AB  - OBJECTIVES: We estimated rates and determinants of hepatitis C virus (HCV)
      testing, infection, and linkage to care among US racial/ethnic minorities.
      METHODS: We analyzed the Racial and Ethnic Approaches to Community Health Across
      the US Risk Factor Survey conducted in 2009-2010 (n = 53,896 minority adults).
      RESULTS: Overall, 19% of respondents were tested for HCV. Only 60% of those
      reporting a risk factor were tested, with much lower rates among Asians reporting
      injection drug use (40%). Odds of HCV testing decreased with age and increased
      with higher education. Of those tested, 8.3% reported HCV infection. Respondents
      with income of $75,000 or more were less likely to report HCV infection than
      those with income less than $25,000. College-educated non-Hispanic Blacks and
      Asians had lower odds of HCV infection than those who did not finish high school.
      Of those infected, 44.4% were currently being followed by a physician, and 41.9%
      had taken HCV medications. CONCLUSIONS: HCV testing and linkage to care among
      racial/ethnic minorities are suboptimal, particularly among those reporting HCV
      risk factors. Socioeconomic factors were significant determinants of HCV testing,
      infection, and access to care. Future HCV testing and prevention activities
      should be directed toward racial/ethnic minorities, particularly those of low
      socioeconomic status.

PMID- 23153152
TI  - Effectiveness of a community health worker cardiovascular risk reduction program
      in public health and health care settings.
AB  - OBJECTIVES: We evaluated whether a program to prevent coronary heart disease
      (CHD) with community health workers (CHWs) would improve CHD risk in public
      health and health care settings. METHODS: The CHWs provided point-of-service
      screening, education, and care coordination to residents in 34 primarily rural
      Colorado counties. The CHWs utilized motivational interviewing and navigated
      those at risk for CHD into medical care and lifestyle resources. A software
      application generated a real-time 10-year Framingham Risk Score (FRS) and
      guideline-based health recommendations while supporting longitudinal caseload
      tracking. We used multiple linear regression analysis to determine factors
      associated with changes in FRS. RESULTS: From 2010 to 2011, among 4743
      participants at risk for CHD, 53.5% received medical or lifestyle referrals and
      698 were retested 3 or more months after screening. We observed statistically
      significant improvements in diet, weight, blood pressure, lipids, and FRS with
      the greatest effects among those with uncontrolled risk factors. Successful phone
      interaction by the CHW led to lower FRS at retests (P = .04). CONCLUSIONS: A CHW
      based program within public health and health care settings improved CHD risk.
      Further exploration of factors related to improved outcomes is needed.

PMID- 23153153
TI  - Nonresponse to a question on self-identified sexual orientation in a public
      health survey and its relationship to race and ethnicity.
AB  - We examined whether nonresponse to the survey question on self-identified sexual
      orientation was associated with race and ethnicity, utilizing Washington State
      Behavioral Risk Factor Surveillance System data. The results of adjusted
      multinomial logistic regression indicated that the nonresponse rates of Asian
      Americans, Hispanics, and African Americans are higher than those of non-Hispanic
      Whites. Innovative ways of measuring sexual orientation to reduce racially and
      ethnically driven bias need to be developed and integrated into public health
      surveys.

PMID- 23153154
TI  - Adversity and syndemic production among men participating in the multicenter AIDS
      cohort study: a life-course approach.
AB  - OBJECTIVES: We tested a theory of syndemic production among men who have sex with
      men (MSM) using data from a large cohort study. METHODS: Participants were 1551
      men from the Multicenter AIDS Cohort Study enrolled at 4 study sites: Baltimore,
      Maryland-Washington, DC; Chicago, Illinois; Los Angeles, California; and
      Pittsburgh, Pennsylvania. Participants who attended semiannual visits from April
      1, 2008, to March 31, 2009, completed an additional survey that captured data
      about events throughout their life course thought to be related to syndemic
      production. RESULTS: Using multivariate analysis, we found that the majority of
      life-course predictor variables (e.g., victimization, internalized homophobia)
      were significantly associated with both the syndemic condition and the component
      psychosocial health outcomes (depressive symptoms, stress, stimulant use, sexual
      compulsivity, intimate partner violence). A nested negative binomial analysis
      showed that the overall life course significantly explained variability in the
      syndemic outcomes (chi(2) = 247.94; P < .001; df = 22). CONCLUSIONS: We
      identified life-course events and conditions related to syndemic production that
      may help to inform innovative interventions that will effectively disentangle
      interconnecting health problems and promote health among MSM.

PMID- 23153155
TI  - Assessment of biases against Latinos and African Americans among primary care
      providers and community members.
AB  - OBJECTIVES: We assessed implicit and explicit bias against both Latinos and
      African Americans among experienced primary care providers (PCPs) and community
      members (CMs) in the same geographic area. METHODS: Two hundred ten PCPs and 190
      CMs from 3 health care organizations in the Denver, Colorado, metropolitan area
      completed Implicit Association Tests and self-report measures of implicit and
      explicit bias, respectively. RESULTS: With a 60% participation rate, the PCPs
      demonstrated substantial implicit bias against both Latinos and African
      Americans, but this was no different from CMs. Explicit bias was largely absent
      in both groups. Adjustment for background characteristics showed the PCPs had
      slightly weaker ethnic/racial bias than CMs. CONCLUSIONS: This research provided
      the first evidence of implicit bias against Latinos in health care, as well as
      confirming previous findings of implicit bias against African Americans. Lack of
      substantive differences in bias between the experienced PCPs and CMs suggested a
      wider societal problem. At the same time, the wide range of implicit bias
      suggested that bias in health care is neither uniform nor inevitable, and
      important lessons might be learned from providers who do not exhibit bias.

PMID- 23153156
TI  - Reproductive rights activism in the post-Roe era.
AB  - Since the US Supreme Court decision legalizing abortion (Roe v Wade), there has
      been a constant and broad attack on all aspects of women's reproductive and
      parenting rights. The consequences have been devastating, especially for women
      whose race, age, legal, or economic status makes them targets of discrimination. 
      At the same time, these threats have galvanized activism. There has been
      tremendous growth in the number of organizations and coalitions working to
      protect abortion rights, as well as advocating a broader reproductive rights,
      health, and justice agenda.  This article describes the major activist trends in
      this period, focusing primarily on those that have been less visible. Documenting
      activist history allows us to draw inspiration and important lessons for the
      future.

PMID- 23153157
TI  - Drewnowski et al. respond.

PMID- 23153158
TI  - Changes in service delivery patterns after introduction of telemedicine provision
      of medical abortion in Iowa.
AB  - OBJECTIVES: We assessed the effect of a telemedicine model providing medical
      abortion on service delivery in a clinic system in Iowa. METHODS: We reviewed
      Iowa vital statistic data and billing data from the clinic system for all
      abortion encounters during the 2 years prior to and after the introduction of
      telemedicine in June 2008 (n = 17,956 encounters). We calculated the distance
      from the patient's residential zip code to the clinic and to the closest clinic
      providing surgical abortion. RESULTS: The abortion rate decreased in Iowa after
      telemedicine introduction, and the proportion of abortions in the clinics that
      were medical increased from 46% to 54%. After telemedicine was introduced, and
      with adjustment for other factors, clinic patients had increased odds of
      obtaining both medical abortion and abortion before 13 weeks' gestation. Although
      distance traveled to the clinic decreased only slightly, women living farther
      than 50 miles from the nearest clinic offering surgical abortion were more likely
      to obtain an abortion after telemedicine introduction. CONCLUSIONS: Telemedicine
      could improve access to medical abortion, especially for women living in remote
      areas, and reduce second-trimester abortion.

PMID- 23153159
TI  - Roe v Wade and the new Jane Crow: reproductive rights in the age of mass
      incarceration.
AB  - All pregnant women, not just those who seek to end a pregnancy, have benefited
      from Roe v Wade. Today's system of mass incarceration makes it likely that if Roe
      is overturned women who have abortions will go to jail.  Efforts to establish
      separate legal "personhood" for fertilized eggs, embryos, and fetuses, however,
      are already being used as the basis for the arrests and detentions of and forced
      interventions on pregnant women, including those who seek to go to term. 
      Examination of these punitive actions makes clear that attacks on Roe threaten
      all pregnant women not only with the loss of their reproductive rights and
      physical liberty but also with the loss of their status as full constitutional
      persons.

PMID- 23153160
TI  - It is time to integrate abortion into primary care.
AB  - The Roe v Wade decision made safe abortion available but did not change the
      reality that more than 1 million women face an unwanted pregnancy every year.
      Forty years after Roe v Wade, the procedure is not accessible to many US women. 
      The politics of abortion have led to a plethora of laws that create enormous
      barriers to abortion access, particularly for young, rural, and low-income women.
      Family medicine physicians and advanced practice clinicians are qualified to
      provide abortion care.  To realize the promise of Roe v Wade, first-trimester
      abortion must be integrated into primary care and public health professionals and
      advocates must work to remove barriers to the provision of abortion within
      primary care settings.

PMID- 23153161
TI  - Gowda et al. respond.

PMID- 23153162
TI  - Ford responds.

PMID- 23153163
TI  - The Calderone Prize in Public Health a legacy of legends.

PMID- 23153164
TI  - Web 2.0 for health promotion: reviewing the current evidence.
AB  - As Web 2.0 and social media make the communication landscape increasingly
      participatory, empirical evidence is needed regarding their impact on and utility
      for health promotion. Following Preferred Reporting Items for Systematic Reviews
      and Meta-Analyses guidelines, we searched 4 medical and social science databases
      for literature (2004-present) on the intersection of Web 2.0 and health. A total
      of 514 unique publications matched our criteria. We classified references as
      commentaries and reviews (n = 267), descriptive studies (n = 213), and pilot
      intervention studies (n = 34). The scarcity of empirical evidence points to the
      need for more interventions with participatory and user-generated features.
      Innovative study designs and measurement methods are needed to understand the
      communication landscape and to critically assess intervention effectiveness. To
      address health disparities, interventions must consider accessibility for
      vulnerable populations.

PMID- 23153165
TI  - Public health in a time of government austerity.

PMID- 23153166
TI  - Impacts of climate change on Caribbean life.

PMID- 23153167
TI  - Semiconductor nanomembranes: a platform for new properties via strain
      engineering.
AB  - New phenomena arise in single-crystal semiconductors when these are fabricated
      in very thin sheets, with thickness at the nanometer scale. We review recent
      research on Si and Ge nanomembranes, including the use of elastic strain sharing,
      layer release, and transfer, that demonstrate new science and enable the
      fabrication of materials with unique properties. Strain engineering produces new
      strained forms of Si or Ge not possible in nature, new layered structures, defect
      free SiGe sheets, and new electronic band structure and photonic properties.
      Through-membrane elastic interactions cause the double-sided ordering of
      epitaxially grown nanostressors on Si nanomembranes, resulting in a spatially and
      periodically varying strain field in the thin crystalline semiconductor sheet.
      The inherent influence of strain on the band structure creates band gap
      modulation, thereby creating effectively a single-element electronic
      superlattice. Conversely, large-enough externally applied strain can make Ge a
      direct-band gap semiconductor, giving promise for Group IV element light sources.

PMID- 23153168
TI  - LaSr3F5(CN2)2: a prototype structure for mixed-valent Eu4F5(CN2)2.
AB  - The new compound LaSr(3)F(5)(CN(2))(2) was prepared and structurally
      characterized as a prototype structure for the remarkably distorted mixed-valent
      compound Eu(4)F(5)(CN(2))(2), which contains four distinct europium ions in the
      structure: one Eu(3+) and three Eu(2+). Instead of repeating the given distorted
      structural pattern, LaSr(3)F(5)(CN(2))(2) forms a structure which can be
      considered as an ideal high-symmetry structure for Eu(4)F(5)(CN(2))(2), due to
      the occupation of La(3+) and Sr(2+) ions on one and the same crystallographic
      position. The crystal symmetry of this structure is an interesting issue to
      compare with what has been previously proposed.

PMID- 23153169
TI  - Barriers faced by Ugandan university students in seeking medical care and sexual
      health counselling: a cross-sectional study.
AB  - BACKGROUND: Meeting the medical and sexual health care needs of young people is
      crucial for sustainable development. In Uganda, youth are faced with a number of
      challenges related to accessing medical care and sexual health counselling
      services. This study sought to investigate the barriers faced by Ugandan
      university students in seeking medical care and sexual health counselling.
      METHODS: This study is part of a cross-sectional survey conducted in 2005 among
      980 students at Mbarara University of Science and Technology. Data was collected
      by means of a self-administered 11-page questionnaire. The barriers encountered
      by respondents in seeking medical care and sexual health counselling were
      classified into three categories reflecting the acceptability, accessibility, or
      availability of services. RESULTS: Two out of five students reported unmet
      medical care needs, and one out of five reported unmet sexual health counselling
      needs. Acceptability of services was the main barrier faced by students for
      seeking medical care (70.4%) as well as for student in need of sexual health
      counselling (72.2%), regardless of age, gender, self-rated health, and rural/peri
      urban or urban residence status. However, barriers differed within the various
      strata. There was a significant difference (p-value 0.01) in barriers faced by
      students originally from rural versus peri-urban/urban areas in seeking medical
      care (acceptability: 64.8%/74.5%, accessibility: 22.0% /12.6%, availability
      13.2%/12.9%, respectively). Students who reported poor self-rated health
      encountered barriers in seeking both medical care and sexual health counselling
      that were significantly different from their other counterparts (p-value 0.001
      and 0.007 respectively). CONCLUSIONS: Barriers faced by students in seeking
      medical and sexual health care should be reduced by interventions aimed at
      boosting confidence in health care services, encouraging young people to seek
      early treatment, and increasing awareness of where they can turn for services.
      The availability of medical services should be increased and waiting times and
      cost reduced for vulnerable groups.

PMID- 23153170
TI  - A fistula flap technique for correction of type II atresia ani and rectovaginal
      fistula in 6 kittens.
AB  - OBJECTIVE: To report a surgical technique and long-term outcomes of type II
      atresia ani (AA) and rectovaginal fistula (RvF) correction, using a fistula flap
      technique in kittens. STUDY DESIGN: Clinical study. ANIMALS: Domestic shorthaired
      female kittens (n = 6) with type II AA-RvF. METHODS: Diagnosis of type II AA-RvF
      was made by clinical examination and vaginography. The anomaly was surgically
      corrected by a fistula flap technique for reconstruction of the anal canal and
      anus, and by vaginoplasty. Kittens were monitored for short and long-term
      complications. RESULTS: All 6 kittens were fecal and urinary continent in the
      immediate postoperative period. Postoperative complications occurred in 2
      kittens: partial dehiscence between the anal and vaginal opening and a stenosis
      at the level of the rectal mucocutaneous anastomosis. Dehiscence healed by second
      intention and stenosis was treated by anoplasty. No long-term complications
      (median follow-up, 12 months; range, 12-17 months) were observed. CONCLUSIONS:
      Reconstruction of the anal canal and anus using the fistula as a local flap in
      combination with a vaginoplasty can be effective to treat feline type II AA and
      RvFs.

PMID- 23153171
TI  - Comparison of batch and column tests for the elution of artificial turf system
      components.
AB  - Synthetic athletic tracks and turf areas for outdoor sporting grounds may release
      contaminants due to the chemical composition of some components. A primary
      example is that of zinc from reused scrap tires (main constituent, styrene
      butadiene rubber, SBR), which might be harmful to the environment. Thus, methods
      for the risk assessment of those materials are required. Laboratory leaching
      methods like batch and column tests are widely used to examine the soil
      groundwater pathway. We tested several components for artificial sporting grounds
      with batch tests at a liquid to solid (LS) ratio of 2 L/kg and column tests with
      an LS up to 26.5 L/kg. We found a higher zinc release in the batch test eluates
      for all granules, ranging from 15% higher to 687% higher versus data from column
      tests for SBR granules. Accompanying parameters, especially the very high
      turbidity of one ethylene propylene diene monomer rubber (EPDM) or thermoplastic
      elastomer (TPE) eluates, reflect the stronger mechanical stress of batch testing.
      This indicates that batch test procedures might not be suitable for the risk
      assessment of synthetic sporting ground components. Column tests, on the other
      hand, represent field conditions more closely and allow for determination of time
      dependent contaminants release.

PMID- 23153172
TI  - Proteome profiling of flax (Linum usitatissimum) seed: characterization of
      functional metabolic pathways operating during seed development.
AB  - Flax (Linum usitatissimum L.) seeds are an important source of food and feed due
      to the presence of various health promoting compounds, making it a nutritionally
      and economically important plant. An in-depth analysis of the proteome of
      developing flax seed is expected to provide significant information with respect
      to the regulation and accumulation of such storage compounds. Therefore, a
      proteomic analysis of seven seed developmental stages (4, 8, 12, 16, 22, 30, and
      48 days after anthesis) in a flax variety, NL-97 was carried out using a
      combination of 1D-SDS-PAGE and LC-MSE methods. A total 1716 proteins were
      identified and their functional annotation revealed that a majority of them were
      involved in primary metabolism, protein destination, storage and energy. Three
      carbon assimilatory pathways appeared to operate in flax seeds. Reverse
      transcription quantitative PCR of selected 19 genes was carried out to understand
      their roles during seed development. Besides storage proteins, methionine
      synthase, RuBisCO and S-adenosylmethionine synthetase were highly expressed
      transcripts, highlighting their importance in flax seed development. Further, the
      identified proteins were mapped onto developmental seed specific expressed
      sequence tag (EST) libraries of flax to obtain transcriptional evidence and 81%
      of them had detectable expression at the mRNA level. This study provides new
      insights into the complex seed developmental processes operating in flax.

PMID- 23153173
TI  - Antioxidant activity and cytotoxicity of Cyrtosperma johnstonii extracts on drug
      sensitive and resistant leukemia and small cell lung carcinoma cells.
AB  - CONTEXT: The number of patients with cancer is increasing. New therapeutic agents
      to overcome drug-resistant tumors are urgently needed. Cyrtosperma johnstonii
      N.E. Br. (Araceae) is used for treatment of cancer in Thai traditional medicine.
      This study aimed to evaluate antioxidant activity and cytotoxicity of C.
      johnstonii extracts on human cancer cells. MATERIALS AND METHODS: Dried powder of
      C. johnstonii rhizomes was extracted with several solvents. The 0.1 mg/ml extract
      solution was tested for antioxidant activity by 2,2'-azinobis-3
      ethylbenzothiazoline-6-sulfonic acid (ABTS) and ferric reducing antioxidant power
      (FRAP) assays. Color formation from 3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide was used to determine cell viability. Standardization
      of the extract was performed by high-performance liquid chromatography (HPLC)
      with photodiode array detector at 254 and 360 nm. Cell cycle arrest was evaluated
      by flow cytometry after 5 min, 12 h and 24 h treated with 20 ug/ml of the acetone
      extract. RESULTS: The acetone extract exhibited the highest phenolic content and
      antioxidant activity (TEAC and EC values = 19.2 +/- 0.14 and 19.2 +/- 0.31 mM/mg,
      respectively). The IC50 values for leukemia ranged from 11 +/- 1 to 29 +/- 3
      ug/ml and from 5 +/- 2 to 6 +/- 0 ug/ml for small cell lung carcinoma cells. Cell
      cycle arrest occurred at the G2/M phase followed by apoptosis. HPLC analysis
      revealed that rutin is the major constituents of the extract. DISCUSSION AND
      CONCLUSION: The acetone extract of C. johnstoni is a promising source of natural
      antioxidants and anticancer. The extract inhibits cancer cells effectively with
      less effect on normal cells.

PMID- 23153174
TI  - Synthetic precursors for TCNQF4(2-) compounds: synthesis, characterization, and
      electrochemical studies of (Pr4N)2TCNQF4 and Li2TCNQF4.
AB  - Careful control of the reaction stoichiometry and conditions enables the
      synthesis of both LiTCNQF(4) and Li(2)TCNQF(4) to be achieved. Reaction of LiI
      with TCNQF(4), in a 4:1 molar ratio, in boiling acetonitrile yields
      Li(2)TCNQF(4). However, deviation from this ratio or the reaction temperature
      gives either LiTCNQF(4) or a mixture of Li(2)TCNQF(4) and LiTCNQF(4). This is the
      first report of the large-scale chemical synthesis of Li(2)TCNQF(4). Attempts to
      prepare a single crystal of Li(2)TCNQF(4) have been unsuccessful, although air
      stable (Pr(4)N)(2)TCNQF(4) was obtained by mixing Pr(4)NBr with Li(2)TCNQF(4) in
      aqueous solution. Pr(4)NTCNQF(4) was also obtained by reaction of LiTCNQF(4) with
      Pr(4)NBr in water. Li(2)TCNQF(4), (Pr(4)N)(2)TCNQF(4), and Pr(4)NTCNQF(4) have
      been characterized by UV-vis, FT-IR, Raman, and NMR spectroscopy, high resolution
      electrospray ionization mass spectrometry, and electrochemistry. The structures
      of single crystals of (Pr(4)N)(2)TCNQF(4) and Pr(4)NTCNQF(4) have been determined
      by X-ray crystallography. These TCNQF(4)(2-) salts will provide useful precursors
      for the synthesis of derivatives of the dianions.

PMID- 23153175
TI  - A randomised comparison of InnoScope and Macintosh laryngoscope in simulated
      difficult tracheal intubation in manikins.
AB  - We conducted a crossover randomised study to evaluate the performance of a novel
      optical stylet, the InnoScope, for tracheal intubation in simulated normal and
      difficult airways. Twenty-five anaesthetists attempted tracheal intubation on a
      SimMan 3G simulator using the InnoScope first followed by the Macintosh
      laryngoscope or vice versa. Three airway scenarios were tested: (1) normal
      airway; (2) difficult airway with swollen pharynx; and (3) limited neck movement.
      In each scenario, the laryngeal view, duration of and success rate for tracheal
      intubation were recorded. Compared with the Macintosh laryngoscope, the use of
      InnoScope increased the percentage of glottic opening seen by 17% in normal
      airway, 23% in the difficult airway and 32% with limited neck movement, p < 0.01.
      Despite this better laryngeal view, successful tracheal intubation achieved with
      the InnoScope (88.0%) was lower than that for the Macintosh laryngoscope (98.7%),
      p = 0.008. Using the InnoScope, tracheal intubation during the first attempt was
      only successful in 48% of cases with difficult airway. In this scenario, the
      median (interquartile range [range]) duration of tracheal intubation was
      significantly longer with [corrected] InnoScope compared with the Macintosh
      laryngoscope, (70 (19-120 [15-120)] s vs 30 [21-58 (15-120)] s, [corrected] p =
      0.01. We conclude that an improved laryngeal view with the use of the InnoScope
      did not translate into better conditions for tracheal intubation.

PMID- 23153176
TI  - Evolution and phylogeny of the mud shrimps (Crustacea: Decapoda) revealed from
      complete mitochondrial genomes.
AB  - BACKGROUND: The evolutionary history and relationships of the mud shrimps
      (Crustacea: Decapoda: Gebiidea and Axiidea) are contentious, with previous
      attempts revealing mixed results. The mud shrimps were once classified in the
      infraorder Thalassinidea. Recent molecular phylogenetic analyses, however,
      suggest separation of the group into two individual infraorders, Gebiidea and
      Axiidea. Mitochondrial (mt) genome sequence and structure can be especially
      powerful in resolving higher systematic relationships that may offer new insights
      into the phylogeny of the mud shrimps and the other decapod infraorders, and test
      the hypothesis of dividing the mud shrimps into two infraorders. RESULTS: We
      present the complete mitochondrial genome sequences of five mud shrimps,
      Austinogebia edulis, Upogebia major, Thalassina kelanang (Gebiidea),
      Nihonotrypaea thermophilus and Neaxius glyptocercus (Axiidea). All five genomes
      encode a standard set of 13 protein-coding genes, two ribosomal RNA genes, 22
      transfer RNA genes and a putative control region. Except for T. kelanang, mud
      shrimp mitochondrial genomes exhibited rearrangements and novel patterns compared
      to the pancrustacean ground pattern. Each of the two Gebiidea species (A. edulis
      and U. major) and two Axiidea species (N. glyptocercus and N. thermophiles) share
      unique gene order specific to their infraorders and analyses further suggest
      these two derived gene orders have evolved independently. Phylogenetic analyses
      based on the concatenated nucleotide and amino acid sequences of 13 protein
      coding genes indicate the possible polyphyly of mud shrimps, supporting the
      division of the group into two infraorders. However, the infraordinal
      relationships among the Gebiidea and Axiidea, and other reptants are poorly
      resolved. The inclusion of mt genome from more taxa, in particular the reptant
      infraorders Polychelida and Glypheidea is required in further analysis.
      CONCLUSIONS: Phylogenetic analyses on the mt genome sequences and the distinct
      gene orders provide further evidences for the divergence between the two mud
      shrimp infraorders, Gebiidea and Axiidea, corroborating previous molecular
      phylogeny and justifying their infraordinal status. Mitochondrial genome
      sequences appear to be promising markers for resolving phylogenetic issues
      concerning decapod crustaceans that warrant further investigations and our
      present study has also provided further information concerning the mt genome
      evolution of the Decapoda.

PMID- 23153177
TI  - Efficacy and safety comparison between liraglutide as add-on therapy to insulin
      and insulin dose-increase in Chinese subjects with poorly controlled type 2
      diabetes and abdominal obesity.
AB  - OBJECTIVE: To assess the efficacy and safety of adding liraglutide to established
      insulin therapy in poorly controlled Chinese subjects with type 2 diabetes and
      abdominal obesity compared with increasing insulin dose. METHODS: A 12-week,
      randomized, parallel-group study was carried out. A total of 84 patients
      completed the trial who had been randomly assigned to either the liraglutide
      added group or the insulin-increasing group while continuing current insulin
      based treatment. Insulin dose was reduced by 0-30% upon the initiation of
      liraglutide. Insulin doses were subsequently adjusted to optimized glycemic
      control. Glycosylated hemoglobin (HbA1c) values, blood glucose, total daily
      insulin dose, body weight, waist circumference, and the number of hypoglycemic
      events and adverse events were evaluated. RESULTS: At the end of study, the mean
      reduction in HbA1c between the liraglutide-added group and the insulin-increasing
      group was not significantly different (1.9% vs. 1.77%, p>0.05). However, the
      percentage of subjects reaching the composite endpoint of HbA1c <= 7.0% with no
      weight gain and no hypoglycemia, was significantly higher in the liraglutide
      added group than in the insulin-increasing group (67% vs. 19%, p<0.001). Add-on
      liraglutide treatment significantly reduced mean body weight (5.62 kg, p<0.01),
      waist circumference (5.70 cm, p<0.01), body mass index (BMI) (1.93 kg/m2, p<0.01)
      and daily total insulin dose (dropped by 66%) during 12-week treatment period,
      while all of these significantly increased with insulin increasing treatment. Add
      on liraglutide treated patients had lower rate of hypoglycemic events and greater
      insulin and oral antidiabetic drugs discontinuation. Gastrointestinal disorders
      were the most common adverse events in the liraglutide added treatment, but were
      transient. CONCLUSIONS: Addition of liraglutide to abdominally obese, insulin
      treated patients led to improvement in glycemic control similar to that achieved
      by increasing insulin dosage, but with a lower daily dose of insulin and fewer
      hypoglycemic events. Adding liraglutide to insulin also induced a significant
      reduction in body weight and waist circumference. Liraglutide combined with
      insulin may be the best treatment option for poorly controlled type 2 diabetes
      and abdominal obesity.

PMID- 23153178
TI  - Infection by chikungunya virus modulates the expression of several proteins in
      Aedes aegypti salivary glands.
AB  - BACKGROUND: Arthropod-borne viral infections cause several emerging and resurging
      infectious diseases. Among the diseases caused by arboviruses, chikungunya is
      responsible for a high level of severe human disease worldwide. The salivary
      glands of mosquitoes are the last barrier before pathogen transmission. METHODS:
      We undertook a proteomic approach to characterize the key virus/vector
      interactions and host protein modifications that occur in the salivary glands
      that could be responsible for viral transmission by using quantitative two
      dimensional electrophoresis. RESULTS: We defined the protein modulations in the
      salivary glands of Aedes aegypti that were triggered 3 and 5 days after an oral
      infection (3 and 5 DPI) with chikungunya virus (CHIKV). Gel profile comparisons
      showed that CHIKV at 3 DPI modulated the level of 13 proteins, and at 5 DPI 20
      proteins. The amount of 10 putatively secreted proteins was regulated at both
      time points. These proteins were implicated in blood-feeding or in immunity, but
      many have no known function. CHIKV also modulated the quantity of proteins
      involved in several metabolic pathways and in cell signalling. CONCLUSION: Our
      study constitutes the first analysis of the protein response of Aedes aegypti
      salivary glands infected with CHIKV. We found that the differentially regulated
      proteins in response to viral infection include structural proteins and enzymes
      for several metabolic pathways. Some may favour virus survival, replication and
      transmission, suggesting a subversion of the insect cell metabolism by
      arboviruses. For example, proteins involved in blood-feeding such as the short
      D7, an adenosine deaminase and inosine-uridine preferring nucleoside hydrolase,
      may favour virus transmission by exerting an increased anti-inflammatory effect.
      This would allow the vector to bite without the bite being detected. Other
      proteins, like the anti-freeze protein, may support vector protection.

PMID- 23153179
TI  - Computational modeling of human coreceptor CCR5 antagonist as a HIV-1 entry
      inhibitor: using an integrated homology modeling, docking, and membrane molecular
      dynamics simulation analysis approach.
AB  - Chemokine receptor 5 (CCR5) is an integral membrane protein that is utilized
      during human immunodeficiency virus type-1 entry into host cells. CCR5 is a G
      protein coupled receptor that contains seven transmembrane (TM) helices. However,
      the crystal structure of CCR5 has not been reported. A homology model of CCR5 was
      developed based on the recently reported CXCR4 structure as template. Automated
      docking of the most potent (14), medium potent (37), and least potent (25) CCR5
      antagonists was performed using the CCR5 model. To characterize the mechanism
      responsible for the interactions between ligands (14, 25, and 37) and CCR5,
      membrane molecular dynamic (MD) simulations were performed. The position and
      orientation of ligands (14, 25, and 37) were found to be changed after MD
      simulations, which demonstrated the ability of this technique to identify binding
      modes. Furthermore, at the end of simulation, it was found that residues
      identified by docking were changed and some new residues were introduced in the
      proximity of ligands. Our results are in line with the majority of previous
      mutational reports. These results show that hydrophobicity is the determining
      factor of CCR5 antagonism. In addition, salt bridging and hydrogen bond contacts
      between ligands (14, 25, and 37) and CCR5 are also crucial for inhibitory
      activity. The residues newly identified by MD simulation are Ser160, Phe166,
      Ser180, His181, and Trp190, and so far no site-directed mutagenesis studies have
      been reported. To determine the contributions made by these residues, additional
      mutational studies are suggested. We propose a general binding mode for these
      derivatives based on the MD simulation results of higher (14), medium (37), and
      lower (25) potent inhibitors. Interestingly, we found some trend for these
      inhibitors such as, salt bridge interaction between basic nitrogen of ligand and
      acidic Glu283 seemed necessary for inhibitory activity. Also, two aromatic
      pockets (pocket I - TM1-3 and pocket II - TM3-6) were linked by the central polar
      region in TM7, and the simulated inhibitors show important interactions with the
      Trp86, Tyr89, Tyr108, Phe112, Ile198, Tyr251, Leu255, and Gln280 and Glu283
      residues. These results shed light on the usage of MD simulation to identify more
      stable, optimal binding modes of the inhibitors. 

PMID- 23153180
TI  - Formation of shish-kebabs in injection-molded poly(L-lactic acid) by application
      of an intense flow field.
AB  - Unlike polyolefins (e.g., isotactic polypropylene), it is still a great challenge
      to form rich shish-kebabs in biodegradable poly(L-lactic acid) (PLLA) because of
      its short chain length and semirigid chain backbone. In the present work, a
      modified injection molding technology, named oscillation shear injection molding,
      was applied to provide an intense shear flow on PLLA melt in mold cavity, in
      order to promote shear-induced crystallization of PLLA. Additionally, a small
      amount of poly(ethylene glycol) (PEG) with flexible chains was introduced for
      improving the crystallization kinetics. Numerous shish-kebabs of PLLA were
      achieved in injection-molded PLLA for the first time. High-resolution scanning
      electronic microscopy and small-angle X-ray scattering showed a structure feature
      of shish-kebabs with a diameter of around 0.7 MUm and a long period of ~20 nm.
      The wide-angle X-ray diffraction results showed that shish-kebabs had more
      ordered crystalline structure of alpha-form. A significant improvement of the
      mechanical properties was obtained; the tensile strength and modulus increased to
      73.7 and 1888 MPa from the initial values of 64.9 and 1684 MPa, respectively,
      meanwhile the ductility is not deteriorated. Interestingly, when shish-kebabs
      form in the PLLA/PEG system, a bamboo-like bionic structure comprising a hard
      skin layer and a soft core develops in injection-molded specimen. This unique
      structure leads to a great balance of mechanical properties, including
      substantial increments of 26, 20, and 112% in the tensile strength, modulus, and
      impact toughness, compared to the control sample. Further exploration will give a
      rich fundamental understanding in the shear-induced crystallization and
      morphology manipulation of PLLA, aiming to achieve superior PLLA products.

PMID- 23153181
TI  - Future directions in psychological assessment: combining evidence-based medicine
      innovations with psychology's historical strengths to enhance utility.
AB  - Assessment has been a historical strength of psychology, with sophisticated
      traditions of measurement, psychometrics, and theoretical underpinnings. However,
      training, reimbursement, and utilization of psychological assessment have been
      eroded in many settings. Evidence-based medicine (EBM) offers a different
      perspective on evaluation that complements traditional strengths of psychological
      assessment. EBM ties assessment directly to clinical decision making about the
      individual, uses simplified Bayesian methods explicitly to integrate assessment
      data, and solicits patient preferences as part of the decision-making process.
      Combining the EBM perspective with psychological assessment creates a hybrid
      approach that is more client centered, and it defines a set of applied research
      topics that are highly clinically relevant. This article offers a sequence of a
      dozen facets of the revised assessment process, along with examples of corollary
      research studies. An eclectic integration of EBM and evidence-based assessment
      generates a powerful hybrid that is likely to have broad applicability within
      clinical psychology and enhance the utility of psychological assessments.

PMID- 23153183
TI  - Cancer stem cells: a review of potential clinical applications.
AB  - CONTEXT: Cancer stem cells (CSCs) comprise a minor cell population in a tumor;
      however, they possess self-renewal capacity and are responsible for tumor
      recurrence and the emerging issue of tumor resistance. Despite recent advances in
      the study of pathogenesis and mechanisms of CSC-mediated disease recurrence and
      multidrug resistance, many questions remain unanswered. OBJECTIVES: To provide an
      overview of CSC theory and to describe major methods of CSC detection and
      isolation, with the emphasis on those techniques that are potentially relevant in
      clinical laboratory practice. Particular attention is given to CSC markers, such
      as cancer testis antigens, which could become promising targets in the
      development of immunotherapy in settings of minimal residual disease. DATA
      SOURCES: The review is based on analysis of peer-reviewed literature cited in
      PubMed, as well as preliminary results of studies conducted in our laboratory.
      CONCLUSIONS: Despite a lack of consensus in the scientific community on research
      methodology, CSCs have demonstrated significant potential as therapeutic targets
      in the treatment of cancer. Further research of CSC biology and markers will
      eventually lead to the development of novel therapeutic approaches for targeting
      these cells to treat resistant and recurrent tumors and minimal residual disease.

PMID- 23153186
TI  - CYP2C metabolism of oral antidiabetic drugs--impact on pharmacokinetics, drug
      interactions and pharmacogenetic aspects.
AB  - INTRODUCTION: The cytochrome P4502C enzymes account for the metabolism of
      approximately 20% of therapeutic drugs including certain oral antidiabetic drugs
      (OADs). AREAS COVERED: This review focuses on the effect of CYP2C enzymes on
      metabolism of sulphonylureas (SUs), meglitinides, and thiazolidinediones (TZDs)
      discussing their impact on pharmacokinetics, drug interactions and toxicological
      profiles. Pharmacogenetic aspects reflecting individual gene variants and
      variable drug effects are also considered. EXPERT OPINION: Genetic polymorphisms
      of CYP2C9 enzymes (*2/*2, *2/*3, *3/*3) influence the glycaemic response to SUs
      and impair their substrate metabolism. Restricted data from small-sized studies
      with heterogenous definitions of hypoglycaemia revealed no clear association
      between CYP2C9 genotypes and the risk of hypoglycaemia. Functional polymorphisms
      of CYP2C8- and CYP2C9 drug metabolizing genes affect markedly pharmacokinetics of
      meglitinides. Compared to wild-type carriers, patients treated with TZDs and
      carrying the common CYP2C8*3 and *4 variants showed a reduced glycaemic control.
      The strong CYP2C8 and OATP1B1 inhibitor gemfibrozil increases substantially the
      plasma concentrations of repaglinide and TZDs. Numerous metabolic drug
      interactions exist between SUs and commonly prescribed drugs, especially anti
      infectives. The complex pharmacokinetic and pharmacogenetic properties and the
      unfavourable short and long term risk profile of glibenclamide and glimepiride
      raise the question whether their use can be justified any longer.

PMID- 23153184
TI  - Molecular characterization of rotavirus isolates from select Canadian pediatric
      hospitals.
AB  - BACKGROUND: We report the first multi-site rotavirus genotype analysis in Canada.
      Prior to this study, there was a dearth of rotavirus G and P genotyping data in
      Canada. Publically funded universal rotavirus vaccination in Canada started in
      2011 and has been introduced by four provinces to date. Uptake of rotavirus
      vaccines in Canada prior to 2012 has been very limited. The aim of this study was
      to describe the genotypes of rotavirus strains circulating in Canada prior to
      widespread implementation of rotavirus vaccine by genotyping samples collected
      from selected paediatric hospitals. Secondly we identified rotavirus strains that
      differed genetically from those included in the vaccines and which could affect
      vaccine effectiveness. METHODS: Stool specimens were collected by opportunity
      sampling of children with gastroenteritis who presented to emergency departments.
      Samples were genotyped for G (VP7) genotypes and P (VP4) genotypes by hemi-nested
      multiplex PCR methods. Phylogenetic analysis was carried out on Canadian G9
      strains to investigate their relationship to G9 strains that have circulated in
      other regions of the world. RESULTS: 348 samples were collected, of which 259
      samples were rotavirus positive and genotyped. There were 34 rotavirus antigen
      immunoassay negative samples genotyped using PCR-based methods. Over the four
      rotavirus seasons, 174 samples were G1P[8], 45 were G3P[8], 22 were G2P[4], 13
      were G9P[8], 3 were G4P[8] and 2 were G9P[4]. Sequence analysis showed that all
      Canadian G9 isolates are within lineage III. CONCLUSIONS: Although a limited
      number of samples were obtained from a median of 4 centres during the 4 years of
      the study, it appears that currently approved rotavirus vaccines are well matched
      to the rotavirus genotypes identified at these hospitals. Further surveillance to
      monitor the emergence of rotavirus genotypes in Canada is warranted.

PMID- 23153187
TI  - Coordination chemistry and reactivity of a cupric hydroperoxide species featuring
      a proximal H-bonding substituent.
AB  - At -90  degrees C in acetone, a stable hydroperoxo complex [(BA)Cu(II)OOH](+) (2)
      (BA, a tetradentate N(4) ligand possessing a pendant -N(H)CH(2)C(6)H(5) group) is
      generated by reacting [(BA)Cu(II)(CH(3)COCH(3))](2+) with only 1 equiv of
      H(2)O(2)/Et(3)N. The exceptional stability of 2 is ascribed to internal H
      bonding. Species 2 is also generated in a manner not previously known in copper
      chemistry, by adding 1.5 equiv of H(2)O(2) (no base) to the cuprous complex
      [(BA)Cu(I)](+). The broad implications for this finding are discussed. Species 2
      slowly converts to a MU-1,2-peroxodicopper(II) analogue (3) characterized by UV
      vis and resonance Raman spectroscopies. Unlike a close analogue not possessing
      internal H-bonding, 2 affords no oxidative reactivity with internal or external
      substrates. However, 2 can be protonated to release H(2)O(2), but only with
      HClO(4), while 1 equiv Et(3)N restores 2.

PMID- 23153188
TI  - The C-seal trial: colorectal anastomosis protected by a biodegradable drain fixed
      to the anastomosis by a circular stapler, a multi-center randomized controlled
      trial.
AB  - BACKGROUND: Anastomotic leakage is a major complication in colorectal surgery and
      with an incidence of 11% the most common cause of morbidity and mortality. In
      order to reduce the incidence of anastomotic leakage the C-seal is developed.
      This intraluminal biodegradable drain is stapled to the anastomosis with a
      circular stapler and prevents extravasation of intracolonic content in case of an
      anastomotic dehiscence.The aim of this study is to evaluate the efficacy of the C
      seal in reducing anastomotic leakage in stapled colorectal anastomoses, as
      assessed by anastomotic leakage leading to invasive treatment within 30  days
      postoperative. METHODS: The C-seal trial is a prospective multi-center randomized
      controlled trial with primary endpoint, anastomotic leakage leading to re
      intervention within 30  days after operation. In this trial 616 patients will be
      randomized to the C-seal or control group (1:1), stratified by center,
      anastomotic height (proximal or distal of peritoneal reflection) and the
      intention to create a temporary deviating ostomy. Interim analyses are planned
      after 50% and 75% of patient inclusion. Eligible patients are at least 18  years
      of age, have any colorectal disease requiring a colorectal anastomosis to be made
      with a circular stapler in an elective setting, with an ASA-classification < 4.
      Oral mechanical bowel preparation is mandatory and patients with signs of
      peritonitis are excluded. The C-seal student team will perform the randomization
      procedure, supports the operating surgeon during the C-seal application and
      achieves the monitoring of the trial. Patients are followed for one year after
      randomization en will be analyzed on an intention to treat basis. DISCUSSION:
      This Randomized Clinical trial is designed to evaluate the effectiveness of the C
      seal in preventing clinical anastomotic leakage.

PMID- 23153189
TI  - A gene expression atlas of the domestic pig.
AB  - BACKGROUND: This work describes the first genome-wide analysis of the
      transcriptional landscape of the pig. A new porcine Affymetrix expression array
      was designed in order to provide comprehensive coverage of the known pig
      transcriptome. The new array was used to generate a genome-wide expression atlas
      of pig tissues derived from 62 tissue/cell types. These data were subjected to
      network correlation analysis and clustering. RESULTS: The analysis presented here
      provides a detailed functional clustering of the pig transcriptome where
      transcripts are grouped according to their expression pattern, so one can infer
      the function of an uncharacterized gene from the company it keeps and the
      locations in which it is expressed. We describe the overall transcriptional
      signatures present in the tissue atlas, where possible assigning those signatures
      to specific cell populations or pathways. In particular, we discuss the
      expression signatures associated with the gastrointestinal tract, an organ that
      was sampled at 15 sites along its length and whose biology in the pig is similar
      to human. We identify sets of genes that define specialized cellular compartments
      and region-specific digestive functions. Finally, we performed a network analysis
      of the transcription factors expressed in the gastrointestinal tract and
      demonstrate how they sub-divide into functional groups that may control cellular
      gastrointestinal development. CONCLUSIONS: As an important livestock animal with
      a physiology that is more similar than mouse to man, we provide a major new
      resource for understanding gene expression with respect to the known physiology
      of mammalian tissues and cells. The data and analyses are available on the
      websites http://biogps.org and http://www.macrophages.com/pig-atlas.

PMID- 23153190
TI  - Neuroprotective and antioxidant potential of terpenoid fraction from Hygrophila
      auriculata against transient global cerebral ischemia in rats.
AB  - CONTEXT: The plant Hygrophila auriculata (K. Schum) Heine. (Acanthaceae) is
      widely used in the Indian System of Medicine as "Rasayana" for treating brain and
      liver diseases. OBJECTIVES: The present study evaluated the in vivo antioxidant
      and neuroprotective effect of aterpenoid rich fraction (TF) from Hygrophila
      auriculata in a rat model of transient global cerebral ischemia (tGCI). MATERIALS
      AND METHODS: Male Wistar rats were grouped as sham control, tGCI control, vitamin
      E (500 mg/kg) and TF (100 & 200 mg/kg) treated groups. Following 7 days of drug
      administration, animals were subjected to tGCI by permanent occlusion of both
      vertebral and transient occlusion of carotid arteries for 10 min followed by
      reperfusion. The neuroprotective effect was assessed by tGCI induced
      neurological, sensory motor deficit in rats. Brain antioxidants such as
      superoxide dismutase (SOD), catalase (CAT) and malondialdehyde (MDA) were
      investigated. Further, a histopathological examination was done in CA1
      hippocampus. RESULTS: tGCI induction resulted in an increase in beam balance
      score (5.1), number of entries in open field (131) and a decrease in time spent
      in rotorod (47 s). In contrast, TF treatment resulted in a significant decrease
      in (p < 0.01) beam balance score (2.9), number of entries (67) and increased time
      spent in rotorod (63.25 s). There was also a significant (p < 0.001) decrease in
      brain SOD and GSH with an increase in MDA. TF treatment resulted in restoration
      of antioxidants and protection of hippocampal CA1 neurons against tGCI insult.
      CONCLUSION: It is concluded that TF from Hygrophila auriculata shows
      neuroprotective potential against tGCI induced oxidative stress.

PMID- 23153191
TI  - Isolation of Pediococcus acidilactici Kp10 with ability to secrete bacteriocin
      like inhibitory substance from milk products for applications in food industry.
AB  - BACKGROUND: Lactic acid bacteria (LAB) can be isolated from traditional milk
      products. LAB that secrete substances that inhibit pathogenic bacteria and are
      resistant to acid, bile, and pepsin but not vancomycin may have potential in food
      applications. RESULTS: LAB isolated from a range of traditional fermented
      products were screened for the production of bacteriocin-like inhibitory
      substances. A total of 222 LAB strains were isolated from fermented milk products
      in the form of fresh curds, dried curds, and ghara (a traditional flavor enhancer
      prepared from whey), and fermented cocoa bean. Eleven LAB isolates that produced
      antimicrobial substances were identified as Lactococcus lactis, Lactobacillus
      plantarum, and Pediococcus acidilactici strains by biochemical methods and 16S
      rDNA gene sequencing. Of these, the cell-free supernatant of Kp10 (P.
      acidilactici) most strongly inhibited Listeria monocytogenes. Further analysis
      identified the antimicrobial substance produced by Kp10 as proteinaceous in
      nature and active over a wide pH range. Kp10 (P. acidilactici) was found to be
      catalase-negative, able to produce beta-galactosidase, resistant to bile salts
      (0.3%) and acidic conditions (pH 3), and susceptible to most antibiotics.
      CONCLUSION: Traditionally prepared fermented milk products are good sources of
      LAB with characteristics suitable for industrial applications. The isolate Kp10
      (P. acidilactici) shows potential for the production of probiotic and functional
      foods.

PMID- 23153193
TI  - Direct observations of parenting and real-time negative affect among adolescent
      smokers and nonsmokers.
AB  - This longitudinal study examined how observations of parental general
      communication style and control with their adolescents predicted changes in
      negative affect over time for adolescent smokers and nonsmokers. Participants
      were 9th- and 10th-grade adolescents (N = 111; 56.8% female) who had all
      experimented with cigarettes and were thus at risk for continued smoking and
      escalation; 36% of these adolescents (n = 40) had smoked in the past month at
      baseline and were considered smokers in the present analyses. Adolescents
      participated separately with mothers and fathers in observed parent-adolescent
      problem-solving discussions to assess parenting at baseline. Adolescent negative
      affect was assessed at baseline, 6 months, and 24 months via ecological momentary
      assessment. Among both smoking and nonsmoking adolescents, escalating negative
      affect significantly increased risk for future smoking. Higher quality maternal
      and paternal communication predicted a decline in negative affect over 1.5 years
      for adolescent smokers but was not related to negative affect for nonsmokers.
      Controlling maternal, but not paternal, parenting predicted escalation in
      negative affect for all adolescents. Findings suggest that reducing negative
      affect among experimenting youth can reduce risk for smoking escalation.
      Therefore, family-based prevention efforts for adolescent smoking escalation
      might consider parental general communication style and control as intervention
      targets. However, adolescent smoking status and parent gender may moderate these
      effects. 

PMID- 23153194
TI  - Modulation of doxorubicin cytotoxicity by resveratrol in a human breast cancer
      cell line.
AB  - BACKGROUND: Breast cancer is the most common cancer in the Arab world and it
      ranked first among Saudi females. Doxorubicin (DOX), an anthracycline antibiotic
      is one of the most effective anticancer agents used to treat breast cancer.
      chronic cardiotoxicity is a major limiting factor of the use of doxorubicin.
      Therefore, our study was designed to assess the role of a natural product
      resveratrol (RSVL) on sensitization of human breast cancer cells (MCF-7) to the
      action of DOX in an attempt to minimize doxorubicin effective dose and thereby
      its side effects. METHODS: Human breast cancer cell line MCF-7, was used in this
      study. Cytotoxic activity of DOX was determined using (sulforhodamine) SRB
      method. Apoptotic cells were quantified after treatment by annexin V-FITC-
      propidium iodide (PI) double staining using flow-cytometer. Cell cycle
      disturbance and doxorubicin uptake were determined after RSVL or DOX treatment.
      RESULTS: Treatment of MCF-7 cells with 15 MUg/ml RSVL either simultaneously or 24
      h before DOX increased the cytotoxicity of DOX, with IC50 were 0.056 and 0.035
      MUg/ml, respectively compared to DOX alone IC50 (0.417 MUg/ml). Moreover, flow
      cytometric analysis of the MCF-7 cells treated simultaneously with DOX (0.5
      MUg/ml) and RSVL showed enhanced arrest of the cells in G0 (80%). On the other
      hand, when RSVL is given 24 h before DOX although there was more increased in the
      cytotoxic effect of DOX against the growth of the cells, however, there was
      decreased in percentage arrest of cells in G0, less inhibition of DOX-induced
      apoptosis and reduced DOX cellular uptake into the cells. CONCLUSION: RSVL
      treatment increased the cytotoxic activity of DOX against the growth of human
      breast cancer cells when given either simultaneously or 24 h before DOX.

PMID- 23153196
TI  - Optimum contribution selection for conserved populations with historic migration.
AB  - BACKGROUND: In recent decades, local varieties of domesticated animal species
      have been frequently crossed with economically superior breeds which has resulted
      in considerable genetic contributions from migrants. Optimum contribution
      selection by maximizing gene diversity while constraining breeding values of the
      offspring or vice versa could eventually lead to the extinction of local breeds
      with historic migration because maximization of gene diversity or breeding values
      would be achieved by maximization of migrant contributions. Therefore, other
      objective functions are needed for these breeds. RESULTS: Different objective
      functions and side constraints were compared with respect to their ability to
      reduce migrant contributions, to increase the genome equivalents originating from
      native founders, and to conserve gene diversity. Additionally, a new method for
      monitoring the development of effective size for breeds with incomplete pedigree
      records was applied. Approaches were compared for Vorderwald cattle, Hinterwald
      cattle, and Limpurg cattle. Migrant contributions could be substantially
      decreased for these three breeds, but the potential to increase the native genome
      equivalents is limited. CONCLUSIONS: The most promising approach was constraining
      migrant contributions while maximizing the conditional probability that two
      alleles randomly chosen from the offspring population are not identical by
      descent, given that both descend from native founders.

PMID- 23153197
TI  - Detecting supercritical CO2 in brine at sequestration pressure with an optical
      fiber sensor.
AB  - Monitoring of sequestered carbon is essential to establishing the environmental
      safety and the efficacy of geological carbon sequestration. Sequestration in
      saline aquifers requires the detection of supercritical CO(2) and CO(2)-saturated
      brine as distinct from the native reservoir brine. Here we demonstrate an all
      optical approach to detect both supercritical CO(2), and saturated brine under
      sequestration conditions. The method employs a long-period grating written on an
      optical fiber with a resonance wavelength that is sensitive to local refractive
      index within a pressure- and temperature-controlled apparatus at 40  degrees C
      and 1400 psi (9.65 MPa). The supercritical CO(2) and brine are clearly
      distinguished by a wavelength shift of 1.149 nm (refractive index difference of
      0.2371). The CO(2)-saturated brine is also detectable relative to brine, with a
      resonance wavelength shift of 0.192 nm (refractive index difference of 0.0396).
      Importantly, these findings indicate the potential for distributed, all-optical
      monitoring of CO(2) sequestration in saline aquifers.

PMID- 23153195
TI  - Pro-death and pro-survival properties of ouabain in U937 lymphoma derived cells.
AB  - BACKGROUND: Epidemiological studies revealed significantly lower mortality rates
      in cancer patients receiving cardiac glycosides, which turned on interest in the
      anticancer properties of these drugs. However, cardiac glycosides have also been
      shown to stimulate cell growth in several cell types. In the present
      investigation we analyzed the pro-death and pro-survival properties of ouabain in
      the human lymphoma derived cell line U937. METHODS: ROS, intracellular Ca++, cell
      cycle were evaluated by loading the cells with fluorescent probes under
      cytofluorimetry. Cell counts and evaluation of trypan blue-excluding cells were
      performed under optic microscope. Protein detection was done by specific
      antibodies after protein separation from cellular lysates by SDS-PAGE and
      transfer blot. RESULTS: High doses of ouabain cause ROS generation, elevation of
      [Ca++]i and death of lymphoma derived U937 cells. Lower doses of OUA activate a
      survival pathway in which plays a role the Na+/Ca++-exchanger (NCX), active in
      the Ca++ influx mode rather than in the Ca++ efflux mode. Also p38 MAPK plays a
      pro-survival role. However, the activation of this MAPK does not appear to depend
      on NCX. CONCLUSION: This investigation shows that the cardiac glycoside OUA is
      cytotoxic also for the lymphoma derived cell line U937 and that can activate a
      survival pathway in which are involved NCX and p38 MAPK. These molecules can
      represent potential targets of combined therapy.

PMID- 23153198
TI  - Glutathionylation induced structural changes in oxy human hemoglobin analyzed by
      backbone amide hydrogen/deuterium exchange and MALDI-mass spectrometry.
AB  - Glutathionyl hemoglobin, a post-translationally modified form of hemoglobin, has
      been reported to serve as a marker of oxidative stress in several clinical
      conditions. This modification causes perturbations in the hemoglobin
      functionality by increasing oxygen affinity and reducing cooperativity. Moreover,
      glutathionylation of sickle hemoglobin was reported to lead to a significant
      reduction in the propensity of sickling of erythrocytes. The root cause of the
      above functional abnormality is not known in detail, as the crystal structure of
      the molecule is yet to be discovered. In this study, we investigated the effects
      of glutathionylation on quaternary structure of hemoglobin using
      hydrogen/deuterium exchange (H/DX) based mass spectrometry. H/DX kinetics of nine
      peptides from alpha and beta globin chains of hemoglobin were analyzed to
      understand the conformational change in deoxy to oxy transition of normal
      hemoglobin and structural perturbations associated with glutathionylation of oxy
      hemoglobin. Significant structural changes brought about by the glutathionylation
      of oxy hemoglobin were observed in the following regions of globin chains: beta86
      102, beta1-14, alpha34-46, beta32-41, beta130-146, beta115-129, beta73-81.
      Isotope exchange kinetics monitored through mass spectrometry is a useful
      technique to understand structural perturbation on post-translational
      modification of proteins in solution phase.

PMID- 23153199
TI  - The application of regional hypothermia using transrectal cooling during radical
      prostatectomy: mitigation of surgical inflammatory damage to preserve continence.
AB  - Preservation of continence and sexual function continues to be a formidable
      quality-of-life issue regarding outcomes after radical prostatectomy. There is
      little argument that physical preservation of the nerves and sphincters is a
      critical component to achieving success in these domains. Previously demonstrated
      factors such as advancing age, deteriorating physical health status, and
      subnormal baseline potency negatively impact outcomes. Our hypothesis, however,
      has been that inflammatory response to surgery has a large impact on surgical
      outcomes of prostatectomy. Trauma-induced inflammation could account for
      variation in recovery despite nearly identical surgery on many patients,
      especially in high-volume surgeons. In other words, we suggest and maintain that
      younger and healthier patients tolerate and/or recover better from the
      trauma/inflammation of surgery. Those who do not recover as well may have altered
      inflammatory response to injury. A common response to decrease inflammation in
      response to physical injury would be as simple as to cool the injury with ice.
      Previous neurologic studies have suggested that using ice during surgical
      intervention can reduce the inflammatory damage. Therefore, we applied this
      concept that preemptive hypothermia could reduce inflammation to the robot
      assisted prostatectomy procedure to potentially lead to improved continence and
      potency outcomes. In 2009, we introduced the concept of regional hypothermia via
      an endorectal cooling balloon during robot-assisted radical prostatectomy (RARP).
      We have published our single institution data demonstrating a significant
      reduction of overall incontinence. Defining continence as zero-pads, our overall
      1-year incontinence has been reduced by 70% (from 13% to 4%). Severe
      incontinence, defined as two or more pads, was likewise reduced by 70% (from 2.9%
      to 0.9%). Regional hypothermia used during the time of surgery represents a novel
      strategy for minimizing inflammation and subsequent muscle and nerve damage in
      RARP.

PMID- 23153200
TI  - Synthesis and structure-activity relationship of (E)-phenoxyacrylic amide
      derivatives as hypoxia-inducible factor (HIF) 1alpha inhibitors.
AB  - A series of (E)-phenoxyacrylic amide derivatives were synthesized and evaluated
      as hypoxia inducible factor (HIF) 1alpha inhibitors. The present structure
      activity relationship study on this series identified the morpholinoethyl
      containing ester 4p as a potent inhibitor of HIF-1alpha under hypoxic conditions
      (IC50=0.12 MUM in a cell-based HRE reporter assay) in HCT116 cells. The
      representative compound 4p suppressed hypoxia-induced HIF-1alpha accumulation and
      targeted gene expression in a dose-dependent manner. The effect of HIF-1alpha
      inhibition by 4p was further demonstrated by its inhibitory activity on in vitro
      tube formation and migration of cells, which may be valuable for development of
      novel therapeutics for cancer and tumor angiogenesis.

PMID- 23153202
TI  - Why condensate drops can spontaneously move away on some superhydrophobic
      surfaces but not on others.
AB  - The coalesce-induced condensate drop motion on some superhydrophobic surfaces
      (SHSs) has attracted increasing attention because of its wide potential
      applications. However, microscopic mechanism of spontaneous motion has not been
      discussed thoroughly. In this study, we fabricated two types of superhydrophobic
      copper surfaces with sisal-like nanoribbon structures and defoliation-like
      nanosheet structures by different wet chemical oxidation process and followed by
      same fluorization treatment. With lotus leaf and butterfly wing as control
      samples, the spontaneous motion phenomenon of condensate drops on these four
      kinds of SHSs was investigated by using optical microscope under ambient
      conditions. The results showed that among all four types of SHSs, only
      superhydrophobic copper surfaces with sisal-like nanoribbon structures showed
      obvious spontaneous motion of condensate drops, especially when the relative
      humidity was higher. The microscopic mechanism of spontaneous motion was
      discussed in relation to the states of condensate drops on different
      nanostructures. It shows that the instantaneous Cassie state of condensed
      droplets prior to coalescence plays a key role in determining whether the
      coalesced drop departs, whereas only SHS possessing nanostructures with small
      enough Wenzel roughness parameter r (at least <2.1) and nanogaps forming high
      enough Laplace pressure favors the formation of the instantaneous Cassie state by
      completing the Wenzel-Cassie transition.

PMID- 23153201
TI  - In vitro antimalarial susceptibility and molecular markers of drug resistance in
      Franceville, Gabon.
AB  - BACKGROUND: Malaria remains a major public health problem, due largely to
      emergence and widespread P. falciparum drug resistance. WHO recommends
      artemisinine combination based therapy (ACT) to overcome P. falciparum drug
      resistance, but reports of declining ACT efficacy have been published. A thorough
      understanding of the molecular bases of P. falciparum resistance to existing
      drugs is therefore needed. The aims of this study were to analyze the in vitro
      sensitivity of P. falciparum field isolates from Franceville, Gabon, to
      chloroquine (CQ), mefloquine (MF), dihydroartemisinine (DHA) and
      monodesethylamodiaquine (MDAQ), and to investigate polymorphisms associated with
      drug resistance. METHODS: We conducted a cross-sectional study of 53 field
      isolates. Field isolates sensitivity to CQ, MF, DHA and MDAQ was assessed using
      the colorimetric DELI test. The Pfmdr1 codons 86 and 1246, Pfcrt (haplotype codon
      72 to 76) and the PfATPAse6 codons 110 and 2694 were analysed by PCR-RFLP.
      Associations between drug sensitivity and parasite gene polymorphisms were
      evaluated with the Chi square test, and routine hematological parameters were
      analyzed with Fisher's exact test implemented with Epinfo software. In all
      statistical tests, significance was assumed at p<0.05. RESULTS: A total of 46 P.
      falciparum isolates were successfully cultured in vitro and their sensitivity was
      tested. The proportions of isolates resistant to CQ, MF and MDAQ were 43.5%,
      23.4% and 56.5%, respectively. Some isolates (23.9%) had DHA IC50 values higher
      than 10 nM. The median IC50 values were 71.67 (interquartile range (IQR, 1
      438.2), 6.59 (IQR, 0.08-96), 64.79 (IQR, 0.09-448) and 6.45 nM (IQR, 0.09-23) for
      CQ, MF, MDAQ and DHA, respectively. The strongest correlation between diminished
      DHA sensitivity and MF resistance was observed (r2=0.73), followed by correlation
      between diminished DHA sensitivity and CQ resistance. Cross-resistance between CQ
      and MF was also observed. The prevalence of the 86Y and 1246Y mutations in
      Pfmdr1, 76T in Pfcrt, and 110A and 2694T in PfATPase6 was respectively 42% and
      17.1%, 97.8%, and 0% and 22.2%. CONCLUSION: These high levels of antimalarial
      drug resistance in Franceville, Gabon, call for reinforced surveillance of drug
      efficacy.

PMID- 23153203
TI  - The borderland of epilepsy: Chairs' Symposium, 10th European Congress on
      Epileptology, London--October 1, 2012. Introduction.

PMID- 23153204
TI  - The startle syndromes: physiology and treatment.
AB  - Startle syndromes are paroxysmal and show stimulus sensitivity, placing them in
      the differential diagnosis of epileptic seizures. Startle syndromes form a
      heterogeneous group of disorders with three categories: hyperekplexia (HPX),
      stimulus-induced disorders, and neuropsychiatric syndromes. HPX is characterized
      by an exaggerated motor startle reflex combined with stiffness and is caused by
      mutations in different parts of the inhibitory glycine receptor, leading to
      brainstem pathology. The preserved consciousness distinguishes it from epileptic
      seizures. Clonazepam is the first-choice therapy. The stimulus-induced disorders
      cover a broad range of epileptic and nonepileptic disorders, and distinguishing
      the two can be difficult. Additional information from electroencephalography
      (EEG) and video registration can help. Many stimulus-induced disorders now have
      an identified gene defect. Antiepileptic drugs, including benzodiazepines, are
      frequently mentioned as the best treatment option. Neuropsychiatric syndromes are
      on the borderland of neurology and psychiatry, and their etiology is poorly
      understood. These syndromes include startle-induced tics, culture-specific
      disorders such as Latah, and functional startle syndromes. The electromyography
      (EMG) startle reflex in these syndromes is characterized by variable recruitment
      patterns and the presence of a second "orienting" response. Treatment options are
      limited, but urgently required. In the clinical setting, the patient's history
      and a (home) video recording together with genetic and electrophysiologic testing
      help to classify these challenging disorders.

PMID- 23153205
TI  - The parasomnias: mechanisms and treatment.
AB  - Although parasomnias should be considered benign conditions without a deleterious
      impact on sleep quality and quantity, especially in children, it is important to
      recognize and properly diagnose these phenomena. Moreover, parasomnias may be
      misdiagnosed as epileptic seizures, in particular seizures with a predominant
      complex motor behavior as seizures occurring in nocturnal frontal lobe epilepsy
      (NFLE), leading to unnecessary and expensive investigations and prolonged and
      unsuccessful treatment. In this article we describe the clinical and
      neurophysiologic features of the most common parasomnias, giving the most
      reliable elements of differential diagnosis between parasomnias and epileptic
      nocturnal seizures, namely the typical seizures occurring in NFLE. The diagnostic
      value of history-taking, video-polysomnography, home video recording, and
      diagnostic scales is discussed. Next we describe the intriguing aspect of the
      frequent coexistence, in the same family and even in the same patients, of
      epileptic and parasomniac attacks, giving a common neurophysiologic
      interpretation. Finally some brief indications to the treatment of parasomnias
      are suggested.

PMID- 23153206
TI  - Migraine in the borderland of epilepsy: "migralepsy" an overlapping syndrome of
      children and adults?
AB  - Gowers gave migraine a place in the borderland of epilepsy, justified by many
      relations and the fact that distinction of these two diseases is difficult.
      Gowers based his ideas on clinical histories from his patients, and he concluded
      that in extremely rare instances one may develop while the other goes on. In
      modern times, patient testimonies of the problem of differentiating migraine from
      epilepsy are given in health-chat Websites. It shows clearly that distinction
      between the two conditions is still problematic and that migralepsy is either
      nonexisting or extremely rare as Gowers noticed.

PMID- 23153207
TI  - Why are antiepileptic drugs used for nonepileptic conditions?
AB  - Antiepileptic drugs (AEDs) are used to treat various nonepileptic central nervous
      system (CNS) disorders, both in neurology and psychiatry. Most AEDs have multiple
      mechanisms of action (MOAs), which include modulation of gamma-aminobutyric acid
      (GABA)ergic and glutamatergic neurotransmission, and alteration of voltage-gated
      ion channels or intracellular signaling pathways. These MOAs may explain the
      efficacy of AEDs in the treatment of bipolar disorder and neuropathic pain.
      Bipolar disorder and epilepsy have some common features, such as their episodic
      nature and associated kindling phenomena, which led to the regulatory approval
      and use of the AEDs carbamazepine (CBZ), valproic acid (VPA), and lamotrigine
      (LTG) in the treatment of bipolar disorder. A major limitation for the
      development of drugs with improved mood-stabilizing activity is the lack of
      knowledge on the mechanism of treatment for bipolar disorder. In contrast to
      epilepsy, no animal models in bipolar disorder are universally accepted and no
      model is able to exhibit the characteristic mood swings. Although most AEDs have
      now been investigated for their mood-stabilizing effects, only three (e.g., VPA,
      CBZ, and LTG) demonstrated clinical efficacy in patients. This suggests that the
      mechanism of drug action in mood disorder and in epilepsy only partially
      overlaps. Peripheral nerve damage leads to the initiation of cellular and
      molecular changes in the nervous system resulting in ectopic, repetitive firing
      perceived as chronic pain. Epileptic seizures are also characterized by
      hyperexcitability of neurons in the brain. The spontaneous electrogenesis in
      neuropathic pain has similarities to that of epilepsy. Alteration in sodium
      channels expression suggests that the mechanism underlying epileptic
      hyperexcitability may be similar to those underlying neuropathic pain. The AEDs
      gabapentin (GBP) and pregabalin (PGB) have become the mainstay of treatment for
      various neuropathic pain syndromes, owing to their ability to inhibit neuronal
      hyperactivity along the pain pathways. One explanation for how GBP and PGB
      relieve neuropathic pain is that they bind selectively to the Ca(+2) -channel
      subunit alpha2-delta in muscle tissue and brain. With 16 new AEDs having entered
      the market since 1990 the antiepileptic market is crowded. Consequently, epilepsy
      alone is not attractive in 2012 to the pharmaceutical industry, even though the
      clinical needs of refractory epilepsy remain unmet. Due to this situation, the
      future design of new AEDs must also include a potential in nonepileptic CNS
      disorders, such as bipolar disorder and neuropathic pain. The global market size
      of each of these two indications is similar to that of epilepsy, whereas they
      both currently have fewer approved drugs for treatment than epilepsy. Therefore,
      a new AED with additional approved indications in bipolar disorder and
      neuropathic pain might have a potential market size three times larger than that
      of epilepsy alone.

PMID- 23153208
TI  - Cardiac syncope.
AB  - Clinicians who diagnose and manage epilepsy frequently encounter diagnoses of a
      nonneurological nature, particularly when assessing patients with transient loss
      of consciousness (T-LOC). Among these, and perhaps the most important, is cardiac
      syncope. As a group, patients with cardiac syncope have the highest likelihood of
      subsequent sudden death, and yet, unlike sudden unexpected death in epilepsy
      (SUDEP) for example, it is the norm for these tragic occurrences to be both
      easily predictable and preventable. In the 12 months following initial
      presentation with cardiac syncope, sudden death has been found to be 6 times more
      common than in those with noncardiac syncope (N Engl J Med 309, 1983, 197). In
      short, for every patient seen with T-LOC, two fundamental aims of the
      consultation are to assess the likelihood of cardiac syncope as the cause, and to
      estimate the risk of future sudden death for the individual. This article aims to
      outline for the noncardiologist how to recognize cardiac syncope, how to tell it
      apart from more benign cardiovascular forms of syncope as well as from seizures
      and epilepsy, and what can be done to predict and prevent sudden death in these
      patients. This is achieved through the assessment triad of a clinical history and
      examination, risk stratification, and 12-lead electrocardiography (ECG).

PMID- 23153209
TI  - Donor-acceptor complexation and dehydrogenation chemistry of aminoboranes.
AB  - A series of formal donor-acceptor adducts of aminoborane (H(2)BNH(2)) and its N
      substituted analogues (H(2)BNRR') were prepared: LB-H(2)BNRR'(2)-BH(3) (LB =
      DMAP, IPr, IPrCH(2) and PCy(3); R and R' = H, Me or tBu; IPr = [(HCNDipp)(2)C:]
      and Dipp = 2,6-iPr(2)C(6)H(3)). To potentially access complexes of molecular
      boron nitride, LB-BN-LA (LA = Lewis acid), preliminary dehydrogenation chemistry
      involving the parent aminoborane adducts LB-H(2)BNH(2)-BH(3) was investigated
      using [Rh(COD)Cl](2), CuBr, and NiBr(2) as dehydrogenation catalysts. In place of
      isolating the intended dehydrogenated BN donor-acceptor complexes, the formation
      of borazine was noted as a major product. Attempts to prepare the
      fluoroarylborane-capped aminoborane complexes, LB-H(2)BNH(2)-B(C(6)F(5))(3), are
      also described.

PMID- 23153210
TI  - Mammalian NPC1 genes may undergo positive selection and human polymorphisms
      associate with type 2 diabetes.
AB  - BACKGROUND: The NPC1 gene encodes a protein involved in intracellular lipid
      trafficking; its second endosomal loop (loop 2) is a receptor for filoviruses. A
      polymorphism (His215Arg) in NPC1 was associated with obesity in Europeans.
      Adaptations to diet and pathogens represented powerful selective forces; thus, we
      analyzed the evolutionary history of the gene and exploited this information for
      the identification of variants/residues of functional importance in human
      disease. METHODS: We performed phylogenetic analysis, population genetic tests,
      and genotype-phenotype analysis in a population from Saudi Arabia. RESULTS:
      Maximum-likelihood ratio tests indicated the action of positive selection on loop
      2 and identified three residues as selection targets; these were confirmed by an
      independent random effects likelihood (REL) analysis. No selection signature was
      detected in present-day human populations, but analysis of nonsynonymous
      polymorphisms showed that a variant (Ile642Met, rs1788799) in the sterol sensing
      domain affects a highly conserved position. This variant and the previously
      described His215Arg polymorphism were tested for association with obesity and
      type 2 diabetes (T2D) in a cohort from Saudi Arabia. Whereas no association with
      obesity was detected, 642Met allele was found to predispose to T2D. A significant
      interaction was noted with sex (P = 0.041), and stratification on the basis of
      gender indicated that the association is driven by men (P = 0.0021, OR = 1.5).
      Notably, two NPC1 haplotypes were also associated with T2D in men (rs1805081
      rs1788799, His-Met: P = 0.0012, OR = 1.54; His-Ile: P = 0.0004, OR = 0.63).
      CONCLUSIONS: Our data indicate a sex-specific effect of NPC1 variants on T2D risk
      and describe putative binding sites for filoviruses entry.

PMID- 23153213
TI  - Thin-film transistors with a graphene oxide nanocomposite channel.
AB  - Graphene oxide (GO) and graphene oxide-zinc oxide nanocomposites (GO-ZnO) were
      used as channel materials on SiO(2)/Si to fabricate thin-film transistors (TFT)
      with an aluminum source and drain. Pure GO-based TFT showed poor field-effect
      characteristics. However, GO-ZnO-nanocomposite-based TFT showed better field
      effect performance because of the anchoring of ZnO nanostructures in the GO
      matrix, which causes a partial reduction in GO as is found from X-ray
      photoelectron spectroscopic data. The field-effect mobility of charge carriers at
      a drain voltage of 1 V was found to be 1.94 cm(2)/(V s). The transport of charge
      carriers in GO-ZnO was explained by a fluctuation-induced tunneling mechanism.

PMID- 23153212
TI  - Anthelmintic potential of three plants used in Nigerian ethnoveterinary medicine.
AB  - CONTEXT: The leaves of Irvingia gabonensis Baill. Ex Lanen (Irvingiaceae), Ficus
      exasperata Vahl (Moraceae), and Vernonia amygdalina Delile (Asteraceae) are
      folklorically used in treating worm infestation in Eastern Nigeria. The
      anthelmintic potential of the ethanol extracts of the leaves of I. gabonensis, F.
      exasperata, and V. amygdalina was investigated. MATERIALS: Acute toxicity tests
      were done in mice using 10, 100, and 1000 mg/kg/bw of extracts. In vitro larval
      assays of Heligmosomoides bakeri larvae at various extract concentrations (125,
      250, and 500 mg/kg) were done. Mice experimentally infected with H. bakeri were
      treated with F. exasperata extract (200, 400, 800 mg/kg). RESULTS: At
      concentrations of 500, 250, and 125 mg/ml F. exasperata caused 100% larval
      mortality. V. amygdalina extract caused 71.43, 57.14, and 57.14% larval deaths
      while I. gabonensis extract caused 71.43, 57.14, and 42.9% larval deaths at the
      same concentrations. There was no significant difference in the fecal egg output,
      packed cell volumes and body weights of the F. exasperata treated mice when
      compared with the infected untreated group. DISCUSSION AND CONCLUSION: Leaf
      extracts of F. exasperata, V. amygdalina, and I. gabonensis exhibited varying
      degrees of larvicidal activities on the infective stage larvae of H. bakeri in
      vitro whereas F. exasperata showed no activity on the parasites in vivo.

PMID- 23153211
TI  - Isolimonic acid interferes with Escherichia coli O157:H7 biofilm and TTSS in
      QseBC and QseA dependent fashion.
AB  - BACKGROUND: E. coli O157:H7 (EHEC) is an important human pathogen. The antibiotic
      treatment of EHEC reportedly results in release of Shiga toxin and is therefore
      discouraged. Consequently, alternative preventive or therapeutic strategies for
      EHEC are required. The objective of the current study was to investigate the
      effect of citrus limonoids on cell-cell signaling, biofilm formation and type III
      secretion system in EHEC. RESULTS: Isolimonic acid and ichangin were the most
      potent inhibitors of EHEC biofilm (IC25=19.7 and 28.3 MUM, respectively) and
      adhesion to Caco-2 cells. The qPCR analysis revealed that isolimonic acid and
      ichangin repressed LEE encoded genes by ~3 to 12 fold. In addition, flhDC was
      repressed by the two limonoids (~3 to 7 fold). Further studies suggested that
      isolimonic acid interferes with AI-3/epinephrine activated cell-cell signaling
      pathway. Loss of biofilm inhibitory activity of isolimonic acid in DeltaqseBC
      mutant, which could be restored upon complementation, suggested a dependence on
      functional QseBC. Additionally, overexpression of qseBC in wild type EHEC abated
      the inhibitory effect of isolimonic acid. Furthermore, the isolimonic acid failed
      to differentially regulate ler in DeltaqseA mutant, while plasmid borne
      expression of qseA in DeltaqseA background restored the repressive effect of
      isolimonic acid. CONCLUSIONS: Altogether, results of study seem to suggest that
      isolimonic acid and ichangin are potent inhibitors of EHEC biofilm and TTSS.
      Furthermore, isolimonic acid appears to interfere with AI-3/epinephrine pathway
      in QseBC and QseA dependent fashion.

PMID- 23153215
TI  - Responses of Lumbriculus variegatus to activated carbon amendments in
      uncontaminated sediments.
AB  - Activated carbon (AC) amendment is a recently developed sediment remediation
      method. The strong hydrophobic organic contaminant sorption efficiency of AC has
      been shown in several studies, but effects on benthic organisms require more
      investigation. The AC induced effects on egestion rate, growth and reproduction
      of Lumbriculus variegatus were studied by applying bituminous coal based AC in
      three different particle size fractions, namely <63 MUm (90%, AC(p)), 63-200 MUm
      (AC(m)) and 1000 MUm (AC(g)), to natural uncontaminated (HS) and artificial
      sediment (AS). Egestion rate, growth and reproduction decreased with increasing
      AC concentration and finer AC particle fractions, effects being stronger on HS
      than on AS sediment. Lipid content in AS was reduced already at the lowest AC
      doses applied (AC(p) and AC(m) 0.05%, AC(g) 0.25%). In addition, hormesis-like
      response was observed in growth (AS) and reproduction (AS, HS) indicating that AC
      may disturb organisms even at very low doses. Potential ecological effects need
      to be further evaluated in an amendment- and site-specific manner.

PMID- 23153214
TI  - A novel strategy for efficient production of anti-V3 human scFvs against HIV-1
      clade C.
AB  - BACKGROUND: Production of human monoclonal antibodies that exhibit broadly
      neutralizing activity is needed for preventing HIV-1 infection, however only a
      few such antibodies have been generated till date. Isolation of antibodies by the
      hybridoma technology is a cumbersome process with fewer yields. Further, the loss
      of unstable or slowly growing clones which may have unique binding specificities
      often occurs during cloning and propagation and the strongly positive clones are
      often lost. This has been avoided by the process described in this paper,
      wherein, by combining the strategy of EBV transformation and recombinant DNA
      technology, we constructed human single chain variable fragments (scFvs) against
      the third variable region (V3) of the clade C HIV-1 envelope. RESULTS: An antigen
      specific phage library of 7000 clones was constructed from the enriched V3-
      positive antibody secreting EBV transformed cells. By ligation of the digested
      scFv DNA into phagemid vector and bio panning against the HIV-1 consensus C and B
      V3 peptides followed by random selection of 40 clones, we identified 15 clones
      that showed V3 reactivity in phage ELISA. DNA fingerprinting analysis and
      sequencing showed that 13 out of the 15 clones were distinct. Expression of the
      positive clones was tested by SDS-PAGE and Western blot. All the 13 anti-V3 scFvs
      showed cross-reactivity against both the clade C and B V3 peptides and did not
      show any reactivity against other unrelated peptides in ELISA. Preliminary
      neutralization assays indicated varying degrees of neutralization of clade C and
      B viruses. EBV transformation, followed by antigen selection of lines to identify
      specific binders, enabled the selection of phage from un-cloned lines for scFv
      generation, thus avoiding the problems of hybridoma technology. Moreover, as the
      clones were pretested for antigen binding, a comparatively small library sufficed
      for the selection of a considerable number of unique antigen binding phage. After
      selection, the phage clones were propagated in a clonal manner. CONCLUSIONS: This
      strategy can be efficiently used and is cost effective for the generation of
      diverse recombinant antibodies. This is the first study to generate anti-V3 scFvs
      against HIV-1 Clade C.

PMID- 23153216
TI  - What is the best diagnostic and therapeutic management strategy for an Addison
      patient during pregnancy?
AB  - A new diagnosis of primary adrenal insufficiency (PAI) during pregnancy is
      extremely rare and difficult to recognize as signs and symptoms such as nausea,
      fatigue and hypotension may resemble features of normal pregnancy. However, if
      the diagnosis is overlooked and steroid replacement delayed, subsequent adrenal
      crisis triggered by hyperemesis gravidarum, fever or delivery can cause severe
      maternal and foetal morbidity and even mortality. In case of clinical suspicion
      of PAI, we recommend to measure paired samples of cortisol and ACTH and, if
      clinically feasible, a short synacthen test. We propose trimester-specific pass
      cut-offs for the short synacthen test that take into account the rise of total
      and also free cortisol during pregnancy. Empirical hydrocortisone treatment
      should never be delayed if the clinical suspicion is high. All pregnant women
      with PAI should be monitored by a team of endocrine and obstetric specialists.
      The third trimester is physiologically associated with a rise not only in total
      but also free cortisol and thus requires regular adjustment of the glucocorticoid
      dose. Mineralocorticoid requirements may change during pregnancy due to the anti
      mineralocorticoid properties of progesterone. As plasma renin physiologically
      increases in pregnancy, monitoring is limited to clinical assessment including
      blood pressure and serum electrolytes. It is crucial that a pregnant woman with
      PAI and her partner are well educated regarding the adjustment of glucocorticoid
      dose in intercurrent illness and that both are trained in hydrocortisone
      emergency injection techniques. The obstetric staff should be provided with clear
      and written guidance for hydrocortisone cover during labour and delivery. With
      the appropriate replacement therapy, PAI patients can expect to have an
      uneventful pregnancy and deliver a healthy infant.

PMID- 23153217
TI  - Percutaneous CT-guided radiofrequency ablation for unresectable hepatocellular
      carcinoma pulmonary metastases.
AB  - PURPOSE: This study aimed to evaluate the safety and efficacy of percutaneous CT
      guided radiofrequency ablation (RFA) for unresectable hepatocellular carcinoma
      pulmonary metastases (HCCPM) and to identify the prognostic factors for survival.
      MATERIALS AND METHODS: We reviewed the medical records of 320 patients with HCCPM
      treated between January 2005 and January 2012. Among them, 29 patients with 68
      lesions of unresectable HCCPM underwent 56 RFA sessions. Safety, local efficacy,
      survival and prognostic factors were evaluated. Survival was analysed using the
      Kaplan-Meier method. Univariate analyses were evaluated by the log-rank test.
      RESULTS: Pneumothorax requiring chest tube placement occurred in five (8.9%,
      5/56) RFA sessions. During the median follow-up period of 23 months (range 6-70),
      18 patients (62.1%, 18/29) died of tumour progression and 11 (37.9%, 11/29) were
      alive. The 1-, 2- and 3-year overall survival rates were 73.4%, 41.1% and 30%,
      respectively. The median progression-free survival was 18 months (95% confidence
      interval (CI) 9.8-26.2) and the median overall survival time was 21 months
      (95%CI, 9.7-32.3). The maximum tumour diameter <=3 cm (p = 0.002), the number of
      pulmonary metastases <=3 (p = 0.014), serum AFP level <=400 ng/mL (p = 0.003),
      and the controlled status of intrahepatic tumour after lung RFA (p = 0.001) were
      favourable prognostic factors for overall survival. CONCLUSIONS: Our study
      indicates that percutaneous CT-guided RFA, as an alternative treatment procedure
      to pulmonary metastasectomy, can be a safe and effective therapeutic option for
      unresectable HCCPM.

PMID- 23153218
TI  - Tolerance for chronic heat exposure is greater in female than male mice.
AB  - PURPOSE: Chronic heat exposure in mice has cellular and physiological effects
      that improve thermal tolerance [1], but also modifies innate immune responses
      with potential adverse consequences [2]. While male and female mice are known to
      respond differently to acute exposure to severe hyperthermia, sex-based
      differences in responses to chronic moderate heat exposure have not been
      reported. The major objective of this study was to compare the tolerance of male
      and female mice for chronic heat exposure. MATERIALS AND METHODS: We used a mouse
      model of 5-day moderate heat exposure (ambient temperature ~37 degrees C) to
      compare the physiological and cellular heat shock response in male and female
      mice. Core temperature, heart rate, and activity were monitored telemetrically
      and heat shock protein levels were measured in brain and lung by western
      blotting. RESULTS: Adult CD-1 female mice maintained a 1.2 degrees C lower core
      temperature (38.31 +/- 0.64 versus 39.51 +/- 0.72 degrees C; p = 0.002),
      experienced less weight loss (1.54 +/- 0.45 versus 4.54 +/- 1.97 g; p = 0.0007),
      and had improved survival (16/16 survived versus 13/21, p < 0.006) than male mice
      of the same age. After 5 days of moderate heat exposure Hsp72 levels in brain and
      lung increased 2.1-fold (p = 0.007) and 5-fold (p = 0.048) in male mice compared
      with 1.3- (p = 0.054) and 1.5-fold (p = 0.134) in female mice. CONCLUSIONS: This
      study reveals previously unknown and potentially important differences between
      male and female mice in physiological and cellular responses to chronic heat
      exposure, which had consequences for survival. Future studies may identify
      biomarkers of differential heat tolerance and treatments to improve heat
      tolerance in humans.

PMID- 23153219
TI  - Enhanced drug delivery in rabbit VX2 tumours using thermosensitive liposomes and
      MRI-controlled focused ultrasound hyperthermia.
AB  - PURPOSE: The efficacy of anticancer drugs in solid tumours is impaired by their
      inability to reach all cancer cells in sufficient concentration to cause
      cytotoxicity. Hyperthermia-triggered release of drugs from thermosensitive
      liposomes can increase tumour drug concentration, but tumour-specific drug
      delivery requires precise temperature control, and effects on microregional
      distribution of anticancer drugs in tumours are unknown. Here we evaluate
      thermally triggered release of doxorubicin in a rabbit tumour model by comparing
      free versus thermosensitive liposomal doxorubicin administered systemically
      during magnetic resonance imaging (MRI)-controlled focused ultrasound
      hyperthermia. MATERIALS AND METHODS: Twelve rabbits with a transplanted VX2
      tumour in each thigh had a 10 mm diameter region in one tumour heated to 43
      degrees C using focused ultrasound with temperature control by MRI thermometry.
      Delivery of doxorubicin to tumours and normal tissues was quantified by
      fluorescence in tissue homogenates, and by fluorescence microscopy. RESULTS:
      Using thermosensitive liposomal doxorubicin (2.5 mg/kg), doxorubicin
      concentrations in heated tumours were 26.7 times higher than in unheated tumours
      (n = 7, p = 0.017, two-sided Wilcoxon signed-rank test). There was no significant
      enhancement with free doxorubicin in heated versus unheated tumours (n = 3, p =
      0.5). With thermosensitive liposomes (8.3 mg/kg), fluorescence microscopy
      demonstrated increased doxorubicin fluorescence in heated versus unheated
      tumours, co-localised with nuclear staining throughout the tumour. CONCLUSIONS:
      Localised image-guided delivery of high concentrations of doxorubicin to cancer
      cells was achieved non-invasively in implanted tumours with temperature-sensitive
      drug carriers and a preclinical MRI-controlled focused ultrasound hyperthermia
      system.

PMID- 23153220
TI  - Heat-inducible transgene expression with transcriptional amplification mediated
      by a transactivator.
AB  - PURPOSE: Control of therapeutic gene expression in tumours is a major goal of
      gene therapy research, as it can restrict cytotoxic gene expression in cancer
      cells. In addition, the combination of hyperthermia with gene therapy through the
      application of heat-inducible vectors can result in considerable improvements in
      therapeutic efficiency. In this study, to combine heat-inducibility with high
      level transgene expression, we developed a heat-inducible transgene expression
      system with transcriptional amplification mediated by a tetracycline-responsive
      transactivator. MATERIALS AND METHODS: A hybrid promoter was generated by placing
      the heat shock protein (HSP) 70B' promoter under the tetracycline-repressor
      responsive element sequence, and a reporter/therapeutic gene expression plasmid
      was constructed by placing a reporter/therapeutic gene under the control of this
      hybrid promoter. RESULTS: When the transactivator expression plasmid harbouring
      an expression cassette of the tetracycline-responsive transactivator gene was co
      transfected with a reporter gene expression plasmid, the reporter gene expression
      was controlled by heat treatment. With this system, high levels of heat-induced
      transgene expression were observed compared to that from the HSP promoter alone
      without the transactivator. Evaluation of in vitro therapeutic effects using
      cancer cell lines revealed that therapeutic gene expression effectively caused
      cell death in a greater percentage of the cells. CONCLUSION: These findings
      indicate that this strategy improves the efficacy of cancer gene therapy.

PMID- 23153221
TI  - HIFU treatment time reduction through heating approach optimisation.
AB  - PURPOSE: This study evaluated the HIFU treatment time reductions attainable for
      several scan paths when optimising the heating approach used (single, discrete
      pulses versus volumetric scanning) and the paths' focal zone heating locations';
      number (N(FZL)), spacings, sequencing order, number of heating cycles
      (N(CYCLES)), and heating times. Also evaluated were the effects of focal zone
      size, increased tissue absorptivity due to heating, and optimisation technique.
      MATERIALS AND METHODS: Treatments of homogeneous constant property tumours were
      simulated for several simple generic tumour shapes and sizes. The concentrated
      heating approach (which delivered the desired thermal dose to each location in
      one discrete heating pulse (N(CYCLES) = 1)) was compared to the fractionated
      heating approach (which dosed the tumour using multiple, shorter pulses
      repeatedly scanned around the heating path (i.e. 'volumetric scanning' with
      N(CYCLES) > 1)). Treatment times were minimised using both simultaneous,
      collective pulse optimisation (which used full a priori knowledge of the
      interacting effects of all pulses) and sequential, single pulse optimisation
      (which used only the information from previous pulses and cooling of the current
      pulse). RESULTS: Optimised concentrated heating always had shorter treatment
      times than optimised fractionated heating, and concentrated heating resulted in
      less normal tissue heating. When large, rapid tissue absorptivity changes were
      present (doubled or quadrupled immediately after heating) the optimal ordering of
      the scan path's sequence of focal zone locations changed. CONCLUSIONS:
      Concentrated heating yields significant treatment time reductions and less normal
      tissue heating when compared to all fractionated scanning approaches, e.g.
      volumetric scanning.

PMID- 23153222
TI  - Mechanical stretch increases the proliferation while inhibiting the osteogenic
      differentiation in dental pulp stem cells.
AB  - Dental pulp stem cells (DPSCs), which can differentiate into several types of
      cells, are subjected to mechanical stress by jaw movement and occlusal forces. In
      this study, we evaluated how the uniaxial mechanical stretch influences
      proliferation and differentiation of DPSCs. DPSCs were isolated and cultured from
      male Sprague-Dawley rats. Cultured DPSCs were identified by surface markers and
      the differentiation capabilities as adipocytes or osteoblasts. To examine the
      response to mechanical stress, uniaxial stretch was exposed to cultured DPSCs. We
      evaluated the impact of stretch on the intracellular signaling, proliferation,
      osteogenic differentiation, and gene expressions of DPSCs. Stretch increased the
      phosphorylation of Akt, ERK1/2, and p38 MAP kinase as well as the proliferation
      of DPSCs. The stretch-induced proliferation of DPSCs was abolished by the
      inhibition of the ERK pathway. On the other hand, stretch significantly decreased
      the osteogenic differentiation of DPSCs, but did not affect the adipogenic
      differentiation. We also confirmed mRNA expressions of osteocalcin and
      osteopontin were significantly suppressed by stretch. In conclusion, uniaxial
      stretch increased the proliferation of DPSCs, while suppressing osteogenic
      differentiation. These results suggest a crucial role of mechanical stretch in
      the preservation of DPSCs in dentin. Furthermore, mechanical stretch may be a
      useful tool for increasing the quantity of DPSCs in vitro for regenerative
      medicine.

PMID- 23153223
TI  - Osteoprotegerin (OPG) protects ovarian cancer cells from TRAIL-induced apoptosis
      but does not contribute to malignant ascites-mediated attenuation of TRAIL
      induced apoptosis.
AB  - BACKGROUND: Resistance to apoptosis is a major problem in ovarian cancer and
      correlates with poor prognosis. Osteoprotegerin (OPG) is a secreted factor in
      malignant ascites and acts as a decoy receptor for receptor activator of NF
      kappaB ligand (RANKL) and tumor necrosis factor-related apoptosis-inducing ligand
      (TRAIL). TRAIL promotes apoptosis in ovarian cancer cells. Ovarian cancer ascites
      attenuate TRAIL-induced apoptosis raising the possibility that OPG contained in
      ascites may abrogate the anti-tumor activity of TRAIL. METHODS: Determination of
      OPG levels in ascites was measured by ELISA. Effect of OPG on TRAIL-induced cell
      death was determined by XTT and colony forming assays in ovarian cancer cell
      lines and primary tumor cells. Apoptosis was assessed by ELISA. RESULTS: We found
      that recombinant OPG and malignant ascites attenuates TRAIL-induced cell death
      and apoptosis in a dose-dependent manner in ovarian cancer cell lines and primary
      ovarian tumor cells. OPG is present at high levels in the ascites of patients
      with ovarian cancer. We found a positive correlation between the levels of OPG in
      ascites and the ability of the ascites to attenuate TRAIL-induced cell death. The
      anti-apoptotic effect of ascites was not reversed by co-incubation with an OPG
      blocking antibody. CONCLUSIONS: OPG and malignant ascites protect ovarian cancer
      cells from TRAIL-induced apoptosis. Although malignant ascites contain high
      levels of OPG, OPG is not a critical component that contributes to ascites
      mediated attenuation of TRAIL-induced apoptosis.

PMID- 23153224
TI  - Two-color fluorescent l-amino acid mimic of tryptophan for probing peptide
      nucleic acid complexes.
AB  - Non-natural amino acids are important tools for site-selective probing of peptide
      properties and interactions. Here, for the first time a fluorescent l-amino acid,
      exhibiting excited-state intramolecular proton transfer (ESIPT) and hydration
      sensitive dual emission, was synthesized. It is an analogue of l-tryptophan
      bearing a slightly larger 2-(2-furyl)-3-hydroxychromone aromatic moiety instead
      of indole. This new amino acid was incorporated through solid-phase synthesis
      into NC(11-55), the zinc finger domain of the HIV-1 nucleocapsid protein, that
      exhibits potent nucleic acid chaperone properties. It was substituted for the
      Trp37 and Ala30 residues, located in the distal finger motif and the linker
      between the fingers of NC(11-55), respectively. Though the highly conserved Trp37
      residue plays a key role in NC(11-55) structure and activity, its substitution
      for the new fluorescent analogue preserved the folding, the nucleic acid binding
      and chaperone activity of the peptide, indicating that the new amino acid can
      conservatively substitute Trp residues. In the presence of oligonucleotides, the
      Trp37-substituted peptide, but not the Ala30 variant, showed strong changes of
      the dual emission corresponding to local dehydration. The results are in line
      with NMR data, suggesting that the fluorescent amino acid interacts similarly to
      Trp37 with the nucleobases and is thus screened from water. Due to the
      exceptional sensitivity of its ESIPT fluorophore to hydration in highly polar
      environment, the new amino acid appears as a promising tool for substituting Trp
      residues and site-selectively investigating peptide-nucleic acid complexes.

PMID- 23153225
TI  - Improving N-terminal protein annotation of Plasmodium species based on signal
      peptide prediction of orthologous proteins.
AB  - BACKGROUND: Signal peptide is one of the most important motifs involved in
      protein trafficking and it ultimately influences protein function. Considering
      the expected functional conservation among orthologs it was hypothesized that
      divergence in signal peptides within orthologous groups is mainly due to N
      terminal protein sequence misannotation. Thus, discrepancies in signal peptide
      prediction of orthologous proteins were used to identify misannotated proteins in
      five Plasmodium species. METHODS: Signal peptide (SignalP) and orthology
      (OrthoMCL) were combined in an innovative strategy to identify orthologous groups
      showing discrepancies in signal peptide prediction among their protein members
      (Mixed groups). In a comparative analysis, multiple alignments for each of these
      groups and gene models were visually inspected in search of misannotated proteins
      and, whenever possible, alternative gene models were proposed. Thresholds for
      signal peptide prediction parameters were also modified to reduce their impact as
      a possible source of discrepancy among orthologs. Validation of new gene models
      was based on RT-PCR (few examples) or on experimental evidence already published
      (ApiLoc). RESULTS: The rate of misannotated proteins was significantly higher in
      Mixed groups than in Positive or Negative groups, corroborating the proposed
      hypothesis. A total of 478 proteins were reannotated and change of signal peptide
      prediction from negative to positive was the most common. Reannotations triggered
      the conversion of almost 50% of all Mixed groups, which were further reduced by
      optimization of signal peptide prediction parameters. CONCLUSIONS: The
      methodological novelty proposed here combining orthology and signal peptide
      prediction proved to be an effective strategy for the identification of proteins
      showing wrongly N-terminal annotated sequences, and it might have an important
      impact in the available data for genome-wide searching of potential vaccine and
      drug targets and proteins involved in host/parasite interactions, as demonstrated
      for five Plasmodium species.

PMID- 23153227
TI  - Organosulfates in humic-like substance fraction isolated from aerosols at seven
      locations in East Asia: a study by ultra-high-resolution mass spectrometry.
AB  - Humic-like substances (HULIS) in ambient aerosols collected at seven locations in
      East Asia were analyzed using electrospray ionization (ESI) coupled with an ultra
      high-resolution mass spectrometer (UHRMS). Locations included a 3 km high
      mountaintop site in Taiwan, rural, suburban, and urban locations in the Pearl
      River Delta (PRD), South China, and in Taiwan. Organosulfates (OS) in the HULIS
      fraction were tentatively identified through accurate mass measurements and MS/MS
      spectra interpretation. In the two mountaintop samples collected in regional
      background atmosphere, little OS were detected, while a few hundred OS formulas
      were identified in the six samples taken in Taiwan and PRD. Many of the OS ions
      were among the most intense peaks in the negative ESI-UHRMS spectra, and their
      elemental formulas were identical to OS derived from biogenic volatile organic
      compounds (BVOCs) (e.g., monoterpenes) that have been identified in chamber
      studies. With OS having less than 6 carbon atoms too hydrophilic to be
      effectively retained in the HULIS fraction, OS containing 10 carbon atoms were
      the most abundant, indicating monoterpenes as important precursors of OS in the
      HULIS fraction. Clear spatial variation in abundance of OS was found among
      different atmospheric environments, with enhanced coupling of BVOCs with
      anthropogenic acidic aerosols observed in the PRD samples over the Taiwan
      samples. The double bond equivalent (DBE) values indicate the majority of OS
      (>90%) in the HULIS fraction are aliphatic. The elemental compositions of OS
      compounds containing N atoms (defined as CHONS) indicate that they are probably
      nitrooxy OS. Some insights into OS formation mechanisms are also gained through
      examining the presence/absence of perceived reactant-product formula pairs in the
      mass spectra. The results suggest the dominant epoxide intermediate pathway for
      formation of OS compounds without N atoms (defined as CHOS) and confirm the more
      readily hydrolyzed characteristics of the --ONO2 group than the --OSO3 group.
      There is a lack of evidence for the epoxide pathway to account for the formation
      of OS in the CHONS subgroup.

PMID- 23153226
TI  - Expression of KCNQ1OT1, CDKN1C, H19, and PLAGL1 and the methylation patterns at
      the KvDMR1 and H19/IGF2 imprinting control regions is conserved between human and
      bovine.
AB  - BACKGROUND: Beckwith-Wiedemann syndrome (BWS) is a loss-of-imprinting pediatric
      overgrowth syndrome. The primary features of BWS include macrosomia,
      macroglossia, and abdominal wall defects. Secondary features that are frequently
      observed in BWS patients are hypoglycemia, nevus flammeus, polyhydramnios,
      visceromegaly, hemihyperplasia, cardiac malformations, and difficulty breathing.
      BWS is speculated to occur primarily as the result of the misregulation of
      imprinted genes associated with two clusters on chromosome 11p15.5, namely the
      KvDMR1 and H19/IGF2. A similar overgrowth phenotype is observed in bovine and
      ovine as a result of embryo culture. In ruminants this syndrome is known as large
      offspring syndrome (LOS). The phenotypes associated with LOS are increased birth
      weight, visceromegaly, skeletal defects, hypoglycemia, polyhydramnios, and
      breathing difficulties. Even though phenotypic similarities exist between the two
      syndromes, whether the two syndromes are epigenetically similar is unknown. In
      this study we use control Bos taurus indicus X Bos taurus taurus F1 hybrid bovine
      concepti to characterize baseline imprinted gene expression and DNA methylation
      status of imprinted domains known to be misregulated in BWS. This work is
      intended to be the first step in a series of experiments aimed at determining if
      LOS will serve as an appropriate animal model to study BWS. RESULTS: The use of
      F1 B. t. indicus x B. t. taurus tissues provided us with a tool to unequivocally
      determine imprinted status of the regions of interest in our study. We found that
      imprinting is conserved between the bovine and human in imprinted genes known to
      be associated with BWS. KCNQ1OT1 and PLAGL1 were paternally-expressed while
      CDKN1C and H19 were maternally-expressed in B. t. indicus x B. t. taurus F1
      concepti. We also show that in bovids, differential methylation exists at the
      KvDMR1 and H19/IGF2 ICRs. CONCLUSIONS: Based on these findings we conclude that
      the imprinted gene expression of KCNQ1OT1, CDKN1C, H19, and PLAGL1 and the
      methylation patterns at the KvDMR1 and H19/IGF2 ICRs are conserved between human
      and bovine. Future work will determine if LOS is associated with misregulation at
      these imprinted loci, similarly to what has been observed for BWS.

PMID- 23153228
TI  - The elusive predisposing polymorphism: MDR1 and lymphoma.

PMID- 23153229
TI  - Allotransplant in relapsed or refractory aggressive T-cell lymphomas:
      retrospective monocentric analysis of 14 patients.

PMID- 23153231
TI  - Is next-generation sequencing an important tool in HPV subtype diagnosis?

PMID- 23153230
TI  - Discovery of (5S,6S,9R)-5-amino-6-(2,3-difluorophenyl)-6,7,8,9-tetrahydro-5H
      cyclohepta[b]pyridin-9-yl 4-(2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridin-1
      yl)piperidine-1-carboxylate (BMS-927711): an oral calcitonin gene-related peptide
      (CGRP) antagonist in clinical trials for treating migraine.
AB  - Calcitonin gene-related peptide (CGRP) receptor antagonists have demonstrated
      clinical efficacy in the treatment of acute migraine. Herein, we describe the
      design, synthesis, and preclinical characterization of a highly potent, oral CGRP
      receptor antagonist BMS-927711 (8). Compound 8 has good oral bioavailability in
      rat and cynomolgus monkey, attractive overall preclinical properties, and shows
      dose-dependent activity in a primate model of CGRP-induced facial blood flow.
      Compound 8 is presently in phase II clinical trials.

PMID- 23153232
TI  - Next-generation sequencing-based testing for cancer mutational landscape
      diversity: clinical implications?

PMID- 23153233
TI  - Cardiac troponin determination in the diagnosis of acute myocardial infarction.

PMID- 23153235
TI  - Detection of lung cancer in bronchial brushing specimens by FISH.
AB  - Bronchial brushing cytology specimens collected during flexible bronchoscopy are
      an important part of the diagnostic workup of patients with indeterminate
      pulmonary nodules. Unfortunately, false-negative diagnoses are not uncommon when
      sampling peripheral nodules, especially small nodules <2 cm in diameter. A number
      of studies have evaluated different FISH probe sets to increase the detection
      rate of lung cancer on bronchial brushings and washings. Most studies have shown
      that FISH with routine cytology increases the sensitivity of lung cancer
      detection over routine cytology alone, while maintaining high specificity. In
      this article, the authors review a recently published three-probe FISH assay for
      the detection of lung cancer in bronchial brushing specimens.

PMID- 23153236
TI  - Multicolor FISH with improved sensitivity and specificity in the diagnosis of
      malignant melanoma.
AB  - The diagnosis of malignant melanoma remains a challenging aspect in the field of
      pathology. In the last years, FISH has become an important tool for the diagnosis
      of melanocytic tumors in addition to conventional microscopy. Benign and
      malignant melanomas can be discriminated using a four-probe FISH assay targeting
      6p25, 6q23, Cep6 and 11q13. Gerami et al. proposed to refine this current probe
      set with the incorporation of chromosome 8q24 and 9p21 probes into the FISH
      assay, and hereby increase sensitivity and specificity for distinguishing between
      benign and malignant melanoma and improve the detection of spitzoid melanomas. In
      this article, the authors evaluate this newly-defined multicolor FISH probe set
      for the diagnosis of malignant melanoma. Optimizing diagnostic tests in malignant
      melanoma are important for current and future management of patients with
      melanocytic proliferations.

PMID- 23153238
TI  - PCR for the molecular diagnosis of mycotic keratitis.
AB  - Mycotic keratitis, an infection of the cornea caused by fungi, is a medical
      emergency, with patients presenting with considerable pain and distress. For
      effective management of the condition, a specific diagnosis must be made rapidly
      to permit early initiation of antifungal therapy. Currently, direct microscopic
      examination and culture of corneal material constitute the 'gold standard' for
      diagnosis. However, rapid, sensitive yet specific tests are needed to detect a
      small number of, or nonviable, fungi. PCR has many potential advantages when used
      as a diagnostic aid for mycotic keratitis; the present review covers these
      advantages, and possible limitations. An expert assessment is also made of
      studies that have used PCR for the diagnosis of mycotic keratitis. The review
      concludes with a Five-year view of the potential impact of PCR in management of
      mycotic keratitis.

PMID- 23153237
TI  - Nucleic acid testing for tuberculosis at the point-of-care in high-burden
      countries.
AB  - Early diagnosis of tuberculosis (TB) facilitates appropriate treatment initiation
      and can limit the spread of this highly contagious disease. However, commonly
      used TB diagnostic methods are slow, often insensitive, cumbersome and
      inaccessible to most patients in TB endemic countries that lack necessary
      resources. This review discusses nucleic acid amplification technologies, which
      are being developed for rapid near patient TB diagnosis, that are in the market
      or undergoing clinical evaluation. They are based on PCR or isothermal methods
      and are implemented as manual assays or partially/fully integrated instrument
      systems, with associated tradeoffs between clinical performance, cost,
      robustness, quality assurance and usability in remote settings by minimally
      trained personnel. Unmet needs prevail for the identification of drug-resistant
      TB and for TB diagnosis in HIV-positive and pediatric patients.

PMID- 23153239
TI  - Recent progress in molecular diagnosis of sleeping sickness.
AB  - This article will review the most recent progress in the molecular diagnosis of
      sleeping sickness and its potential role in patient management and disease
      control. While PCR remains restricted to research and reference laboratories,
      promising alternative molecular platforms have emerged over the last few years.
      Several loop-mediated isothermal amplification assays have been developed for
      detection and identification of the parasite with reported high analytical
      sensitivity and specificity. Simplified loop-mediated isothermal amplification
      formats have been designed and are undergoing evaluation studies in the field.
      Accurate diagnosis based on specific detection of the parasite's ribosomal RNA
      has been made possible by the isothermal nucleic acid sequence-based
      amplification and by direct hybridization with fluorescent detection probes. In
      addition to the technological progress, the authors also discuss the diagnostic
      performance of molecular tests in the most recent clinical evaluation studies and
      briefly present some viewpoints for the near future.

PMID- 23153240
TI  - Real-time PCR as a diagnostic tool for bacterial diseases.
AB  - In recent years, quantitative real-time PCR tests have been extensively developed
      in clinical microbiology laboratories for routine diagnosis of infectious
      diseases, particularly bacterial diseases. This molecular tool is well-suited for
      the rapid detection of bacteria directly in clinical specimens, allowing early,
      sensitive and specific laboratory confirmation of related diseases. It is
      particularly suitable for the diagnosis of infections caused by fastidious growth
      species, and the number of these pathogens has increased recently. This method
      also allows a rapid assessment of the presence of antibiotic resistance genes or
      gene mutations. Although this genetic approach is not always predictive of
      phenotypic resistances, in specific situations it may help to optimize the
      therapeutic management of patients. Finally, an approach combining the detection
      of pathogens, their mechanisms of antibiotic resistance, their virulence factors
      and bacterial load in clinical samples could lead to profound changes in the care
      of these infected patients.

PMID- 23153241
TI  - Methylation of tumor suppressor microRNAs: lessons from lymphoid malignancies.
AB  - miRNAs are a group of small noncoding RNAs measuring 19-25 nucleotides. Sequence
      specific binding of miRNAs to the 3' untranslated regions of target genes leads
      to translational repressions. Dysregulation of miRNA expression involved in
      cancer can be triggered by multiple mechanisms including aberrant DNA methylation
      of the miRNA gene promoter. Of note, DNA methylation of tumor suppressor miRNAs
      has been implicated in various human cancers. Moreover, miRNA silencing mediated
      by aberrant promoter DNA methylation can potentially be reversed by
      hypomethylating agents, and hence may pose a new therapeutic target in cancer. In
      this review, the authors will focus on the aberrant methylation of miRNAs in the
      pathogenesis of lymphoid malignancies including chronic lymphocytic leukemia,
      multiple myeloma and acute lymphoblastic leukemia.

PMID- 23153242
TI  - Role of fatty acid-based functional lipidomics in the development of molecular
      diagnostic tools.
AB  - Lipids are molecules with different structures which have the feature of water
      insolubility in common. They have very important biological roles within
      structural, functional and signaling activities that have recently received
      renewed attention from life science research. Lipidomics considers the structural
      and functional roles played by lipids, but also their in vivo changes due to
      metabolic or degradation pathways, as well as their biological consequences. In
      this context, the dynamic vision of phospholipid metabolism and, in particular,
      fatty acid transformations combine with nutritional aspects and health
      consequences, providing important information for molecular medicine. Fatty acid
      based functional lipidomics can be successfully applied to the follow-up of human
      lipid profiles under normal and pathological conditions, and this review provides
      several examples of this powerful molecular diagnostic tool, which is expected to
      have a strong influence on biomedical research in the 21st century.

PMID- 23153244
TI  - Highlights, predictions, and changes.
AB  - Recent literature highlights at Retrovirology are described. Predictions are made
      regarding "hot" retrovirology research trends for the coming year based on recent
      journal access statistics. Changes in Retrovirology editor and the frequency of
      the Retrovirology Prize are announced.

PMID- 23153245
TI  - Association of IL-18 polymorphisms with rheumatoid arthritis and systemic lupus
      erythematosus in Asian populations: a meta-analysis.
AB  - BACKGROUND: Interleukin (IL)-18, an important proinflammatory cytokine, plays a
      potential pathological role in rheumatoid arthritis (RA) and systemic lupus
      erythematosus (SLE). Studies on the relationship of IL-18 gene promoter rs1946518
      (-607A/C) polymorphism, rs187238 (-137G/C) polymorphism with RA and SLE are
      inconclusive. The aim of this study was to get a more precise estimation of the
      relationship in Asian populations. METHODS: Meta-analysis was conducted on the
      associations between the IL-18 (-607A/C and -137G/C) polymorphisms and RA and
      SLE, using; (1) allele contrast, (2) dominant, and (3) recessive models. A total
      of 11 studies were included in this study. RESULTS: For the relationship of IL-18
      rs1946518 polymorphism with RA (additive model: OR=0.752, 95%CI=0.562-1.006;
      dominant model: OR=0.730, 95%CI =0.479-1.113; recessive model: OR=0.537,
      95%CI=0.271-1.064) and SLE (additive model: OR=0.684, 95%CI=0.455-1.028; dominant
      model: OR=0.645, 95%CI=0.368-1.130; recessive model: OR=0.672, 95%CI =0.447
      1.010), no significant association with RA and SLE risk can be found under all
      genetic models in Asian populations. However, significant associations were
      observed in Chinese population for both RA ((OR=0.688, 95%CI =0.532-0.889) and
      SLE (OR=0.606, 95%CI =0.396-0.930) under additive model. For the relationship
      between IL-18 rs187238 polymorphism and RA or SLE, there was no significant
      association detected in all genetic models, even in Chinese population.
      CONCLUSIONS: This meta-analysis indicates that the IL-18-607A/C polymorphism may
      confer susceptibility to RA and SLE in Chinese population, but not all Asians.

PMID- 23153246
TI  - Phylogenetic and experimental evidence for host-specialized cryptic species in a
      biotrophic oomycete.
AB  - Assortative mating resulting from host plant specialization has been proposed to
      facilitate rapid ecological divergence in biotrophic plant pathogens. Downy
      mildews, a major group of biotrophic oomycetes, are prime candidates for testing
      speciation by host plant specialization. Here, we combined a phylogenetic and
      morphological approach with cross-pathogenicity tests to investigate host plant
      specialization and host range expansion in grapevine downy mildew. This
      destructive disease is caused by Plasmopara viticola, an oomycete endemic to
      North America on wild species and cultivated grapevines. Multiple genealogies and
      sporangia morphology provide evidence that P. viticola is a complex of four
      cryptic species, each associated with different host plants. Cross-inoculation
      experiments showed complete host plant specialization on Parthenocissus
      quinquefolia and on Vitis riparia, whereas cryptic species found on V.
      aestivalis, V. labrusca and V. vinifera were revealed to be less specific. We
      reconstructed the recent host range expansion of P. viticola from wild to
      cultivated grapevines, and showed that it was accompanied by an increase in
      aggressiveness of the pathogen. This case study on grapevine downy mildew
      illustrates how biotrophic plant pathogens can diversify by host plant
      specialization and emerge in agrosystems by shifting to cultivated hosts. These
      results might have important implications for viticulture, including breeding for
      resistance and disease management.

PMID- 23153247
TI  - PMRD: a curated database for genes and mutants involved in plant male
      reproduction.
AB  - BACKGROUND: Male reproduction is an essential biological event in the plant life
      cycle separating the diploid sporophyte and haploid gametophyte generations,
      which involves expression of approximately 20,000 genes. The control of male
      reproduction is also of economic importance for plant breeding and hybrid seed
      production. With the advent of forward and reverse genetics and genomic
      technologies, a large number of male reproduction-related genes have been
      identified. Thus it is extremely challenging for individual researchers to
      systematically collect, and continually update, all the available information on
      genes and mutants related to plant male reproduction. The aim of this study is to
      manually curate such gene and mutant information and provide a web-accessible
      resource to facilitate the effective study of plant male reproduction.
      DESCRIPTION: Plant Male Reproduction Database (PMRD) is a comprehensive resource
      for browsing and retrieving knowledge on genes and mutants related to plant male
      reproduction. It is based upon literature and biological databases and includes
      506 male sterile genes and 484 mutants with defects of male reproduction from a
      variety of plant species. Based on Gene Ontology (GO) annotations and literature,
      information relating to a further 3697 male reproduction related genes were
      systematically collected and included, and using in text curation, gene
      expression and phenotypic information were captured from the literature. PMRD
      provides a web interface which allows users to easily access the curated
      annotations and genomic information, including full names, symbols, locations,
      sequences, expression patterns, functions of genes, mutant phenotypes, male
      sterile categories, and corresponding publications. PMRD also provides mini tools
      to search and browse expression patterns of genes in microarray datasets, run
      BLAST searches, convert gene ID and generate gene networks. In addition, a
      Mediawiki engine and a forum have been integrated within the database, allowing
      users to share their knowledge, make comments and discuss topics. CONCLUSION:
      PMRD provides an integrated link between genetic studies and the rapidly growing
      genomic information. As such this database provides a global view of plant male
      reproduction and thus aids advances in this important area.

PMID- 23153248
TI  - Two-stage amplification of receptors using a multilevel orthogonal/simultaneous
      dynamic combinatorial library.
AB  - Sequential activation of different reversible exchange reactions in a dynamic
      combinatorial library allows directed exploration of the chemical space:
      initially a macrocyclic scaffold is selected by the template and finally side
      chain and conformational constrains are introduced into such a scaffold.

PMID- 23153249
TI  - Computational design of an alpha-gliadin peptidase.
AB  - The ability to rationally modify enzymes to perform novel chemical
      transformations is essential for the rapid production of next-generation protein
      therapeutics. Here we describe the use of chemical principles to identify a
      naturally occurring acid-active peptidase, and the subsequent use of
      computational protein design tools to reengineer its specificity toward
      immunogenic elements found in gluten that are the proposed cause of celiac
      disease. The engineered enzyme exhibits a k(cat)/K(M) of 568 M(-1) s(-1),
      representing a 116-fold greater proteolytic activity for a model gluten
      tetrapeptide than the native template enzyme, as well as an over 800-fold switch
      in substrate specificity toward immunogenic portions of gluten peptides. The
      computationally engineered enzyme is resistant to proteolysis by digestive
      proteases and degrades over 95% of an immunogenic peptide implicated in celiac
      disease in under an hour. Thus, through identification of a natural enzyme with
      the pre-existing qualities relevant to an ultimate goal and redefinition of its
      substrate specificity using computational modeling, we were able to generate an
      enzyme with potential as a therapeutic for celiac disease.

PMID- 23153251
TI  - The effect of a carrier phrase on hearing aid amplification of single words in
      quiet.
AB  - OBJECTIVE: A common method to assess the functional benefit of hearing aids is by
      measuring the performance-intensity curve of single words in quiet with and
      without hearing aids. Currently, virtually all hearing aids use signal
      processing, which may have a marked effect on gain as a function of time. Thus,
      hearing-aid behavior may be different for a word presented in isolation compared
      to the same word preceded by a carrier phrase, which is a closer replication of
      natural conversation. The present research was conducted to assess this
      difference. DESIGN: In a hearing-aid test box, speech materials were routed
      through hearing aids and the output was recorded with a 2cc coupler. STUDY
      SAMPLE: Seven different hearing aids were programmed according to the
      manufacturer's fitting rules, using a given hearing loss. RESULTS: Depending on
      the hearing aid, and the hearing-aid setting, differences in the overall level of
      the hearing-aid processed words ranged from 1.5 to 3.5 dB. Differences were due
      to slow attack times in amplitude compression. CONCLUSIONS: Although differences
      were small for most hearing aids, the use of a carrier phrase should be
      considered in speech intelligibility tests to ensure that hearing-aid performance
      closer reflects that in real life.

PMID- 23153250
TI  - MTMDAT-HADDOCK: high-throughput, protein complex structure modeling based on
      limited proteolysis and mass spectrometry.
AB  - BACKGROUND: MTMDAT is a program designed to facilitate analysis of mass
      spectrometry data of proteins and biomolecular complexes that are probed
      structurally by limited proteolysis. This approach can provide information about
      stable fragments of multidomain proteins, yield tertiary and quaternary structure
      data, and help determine the origin of stability changes at the amino acid
      residue level. Here, we introduce a pipeline between MTMDAT and HADDOCK, that
      facilitates protein-protein complex structure probing in a high-throughput and
      highly automated fashion. RESULTS: A new feature of MTMDAT allows for the direct
      identification of residues that are involved in complex formation by comparing
      the mass spectra of bound and unbound proteins after proteolysis. If 3D
      structures of the unbound components are available, this data can be used to
      define restraints for data-driven docking to calculate a model of the complex. We
      describe here a new implementation of MTMDAT, which includes a pipeline to the
      data-driven docking program HADDOCK, thus streamlining the entire procedure. This
      addition, together with usability improvements in MTMDAT, enables high-throughput
      modeling of protein complexes from mass spectrometry data. The algorithm has been
      validated by using the protein-protein interaction between the ubiquitin-binding
      domain of proteasome component Rpn13 and ubiquitin. The resulting structural
      model, based on restraints extracted by MTMDAT from limited proteolysis and
      modeled by HADDOCK, was compared to the published NMR structure, which relied on
      twelve unambiguous intermolecular NOE interactions. The MTMDAT-HADDOCK structure
      was of similar quality to structures generated using only chemical shift
      perturbation data derived by NMR titration experiments. CONCLUSIONS: The new
      MTMDAT-HADDOCK pipeline enables direct high-throughput modeling of protein
      complexes from mass spectrometry data. MTMDAT-HADDOCK can be downloaded from
      http://www.ifm.liu.se/chemistry/molbiotech/maria_sunnerhagens_group/mtmdat/togeth
      r with the manual and example files. The program is free for academic/non
      commercial purposes.

PMID- 23153252
TI  - The equivalence of acceptable noise level (ANL) with English, Mandarin, and non
      semantic speech: a study across the U.S. and Taiwan.
AB  - OBJECTIVE: Acceptable noise level (ANL) determines the maximum noise level that a
      listener is willing to accept while listening to speech. The objective of this
      study was to determine the equivalence of ANL measured using different speech
      stimuli for native speakers who lived in the U.S. and Taiwan. DESIGN: ANLs were
      measured using English, Mandarin, and the international speech test signal (ISTS)
      at each site. The same babble noise was used across speech stimuli. The ANLs were
      considered equivalent if the difference was unlikely to be greater than 3 dB.
      STUDY SAMPLE: Thirty adults with normal hearing were recruited at each site.
      RESULTS: For each site, the equivalence test suggested that the native-language
      and foreign-language ANLs were equivalent. Between the two sites, ANLs measured
      using the listener's native language were also equivalent. Although the ISTS ANL
      obtained within each site was equivalent to, and highly correlated to, the native
      language ANL, the data were unable to confirm the equivalence of the ISTS ANLs
      obtained from the two sites. CONCLUSIONS: The results suggested the possibility
      of directly comparing ANL measures carried out in different countries using
      different languages. However, it remains unclear if the ISTS can serve as an
      international ANL stimulus.

PMID- 23153253
TI  - Comparing statistics for objective detection of transient and steady-state evoked
      responses in newborns.
AB  - OBJECTIVE: Receiver operating characteristic (ROC) methodology was used to
      compare the performance of different statistics in the automatic detection of
      multiple auditory steady-state responses (MSSR) and click auditory brainstem
      responses (cABR). STUDY SAMPLE: Thirty-five healthy newborns tested within the
      first two weeks of birth. DESIGN: In each case cABR and MSSR (0.5 and 2 kHz) were
      recorded with and without acoustic stimulation, using AUDIX equipment. With this
      test sample of recordings, ROC curves were evaluated separately for each
      statistic evaluated: (1) the standard deviation ratio (SDR) and the correlation
      coefficient ratio (CCR) for the cABR; (2) the Hotelling T2 (HT2) and circular T2
      (CT2) for the MSSR. RESULTS: All objective detection methods performed well
      (areas under ROC (AUC) > 0.9). The MSSR statistics showed significantly larger
      AUCs at both frequencies (HT2: 0.98 and 1; CT2: 0.96 and 0.99) than the cABR
      measures (SDR: 0.91 and CCR: 0.92). The HT2 hits rate was the highest (97-100% at
      0.5 and 2 kHz) for fixed false alarms rates of both 10 and 20%. CONCLUSIONS: This
      superiority of performance of T2-like statistics, reflecting inherent advantages
      of MSSR analysis for automation, warrants serious consideration for further
      development of newborn screening technology.

PMID- 23153254
TI  - Phytochemical and in vitro total antioxidant capacity analyses of peel extracts
      of different cultivars of Cucumis melo and Citrullus lanatus.
AB  - CONTEXT: Cucumis melo Linn. (Cucurbitaceae) and Citrullus lanatus Thunb.
      (Cucurbitaceae) are desert vegetables popular for their nutritional value and
      year round availability. The pulp and seeds of these plants are used for dietary
      purposes or as medications for certain ailments in the folk medicinal system.
      Peels of the fruit are either wasted or used as feed of grazing animals.
      OBJECTIVE: A detailed investigation regarding the chemical constituents and
      antioxidative analyses of the peel extract of fully ripened fruits from different
      cultivars of the two vegetables was carried out here for the first time.
      MATERIALS AND METHODS: Chemical constituents of the peel extracts of C. melo and
      C. lanatus cultivars in methanol, 1-butanol, chloroform and n-hexane were
      analysed by gas chromatography-mass spectrometry (GC-MS) and the antioxidative
      properties were evaluated using standard in vitro antioxidative assays. RESULTS:
      The results demonstrated large variation in the chemical constituents of the
      extracts including alkanes, saturated and unsaturated fatty acids and their
      esters, cyclic ketones, aldehydes, phenolic compounds and anthocyanin
      derivatives. Total phenolic content ranged from 2.96-0.85 mg/L gallic acid
      equivalents for different extracts. DISCUSSION AND CONCLUSION: Employing GC-MS
      analyses and standard in vitro antioxidative assays, the data presented here
      clearly demonstrate the potency of C. melo and C. lanatus extracts as antioxidant
      and radical scavenger plants which may be used as good sources of natural
      antioxidants. The peels of both the plants can be added to the diet at various
      stages to compensate food shortage and dietary deficiency problems of living
      beings.

PMID- 23153255
TI  - A family of binuclear dysprosium(III) radical compounds with magnetic relaxation
      in ON and OFF states.
AB  - Four binuclear dysprosium compounds incorporating the radical ligand 2-(4
      oxidopyridyl)-4,4,5,5-tetramethylimidazolin-1-oxyl-3-oxide (PyNONIT) have been
      successfully synthesized under appropriate conditions. Centrosymmetric bimetallic
      Dy(2)O(2) cores in all of the compounds through double-MU(2)-oxygen atoms of the
      N-oxide groups are realized in a metal-radical approach for the first time.
      Dimers 1 and 2, of the same formula {[Dy(hfac)(3)(PyNONIT)](2)}(2) (hfac =
      hexafluoroacetylacetonate) but obtained by different methods, which contain
      almost identical local symmetry of D(4d) and Dy-(O)(2)-Dy bridging fashion,
      however, display no out-of-phase alternating-current (ac) signal for 1 and slow
      relaxation of the magnetization for 2 corresponding to the difference of the
      crystal packing mode. The adduct
      ([Dy(hfac)(3)(PyNONIT)](2)[Dy(0.5)(hfac)(1.5)(H(2)O)](2)) (3) consists of two
      items, the dimer [Dy(hfac)(3)(PyNONIT)](2) and the monomer
      [Dy(hfac)(3)(H(2)O)(2)], where the symmetry of Dy(III) ion in Dy(2)O(2) decreases
      to D(2d), showing slow relaxation of the magnetization at lower temperature.
      Interestingly, a moisture-mediated reversible solid transformation between 1 and
      ([Dy(hfac)(3)(H(2)O)(PyNONIT)](2)) (4) has been investigated. Spongelike 1 can
      undergo a transition from eight to nine coordination at room temperature through
      hydration. A different coordination field is mostly responsible for no ac signal
      noticed for 4. The structural diversity of the Dy(2) family provides an
      opportunity to expand the investigation on 4f single-molecule magnets. Approaches
      that the relaxation of the supramolecular dimer can be tuned to ON and OFF states
      modulated by the packing mode and ligand field are presented.

PMID- 23153256
TI  - Effect of relative humidity on the migration of benzophenone from paperboard into
      the food simulant Tenax(r) and modelling hereof.
AB  - The aim of this study was to investigate the effect of relative humidity on the
      migration of benzophenone from paperboard into the food simulant Tenax(r).
      Kinetic migration investigations were carried out with three relative humidities
      in the interval between 39% and >73%. All investigations were carried out at a
      constant temperature of 34 degrees C. It was found that the migration of
      benzophenone after more than 30 days was 4.8 times higher at a relative humidity
      of 64%-71%, and 7.3 times higher at a relative humidity of >73%, compared with
      that at a relative humidity of 39%-49%. Diffusion and partition coefficients were
      derived from the results by using a software for modelling migration in
      multilayer materials. Both the diffusion coefficient and the partition
      coefficient, between paperboard and Tenax(r), decrease with increasing relative
      humidity. The experimental results were correctly modelled only when the
      paperboard was regarded as a one-layer system as compared with a two-layer
      system: where the main part of the paperboard (B1) has a high diffusion rate and
      a thin part of the paperboard (B2) in contact with the foodstuff has a lower
      diffusion rate.

PMID- 23153257
TI  - Quantitative evaluation of bioorthogonal chemistries for surface
      functionalization of nanoparticles.
AB  - We present here a highly efficient and chemoselective liposome functionalization
      method based on oxime bond formation between a hydroxylamine and an aldehyde
      modified lipid component. We have conducted a systematic and quantitative
      comparison of this new approach with other state-of-the-art conjugation reactions
      in the field. Targeted liposomes that recognize overexpressed receptors or
      antigens on diseased cells have great potential in therapeutic and diagnostic
      applications. However, chemical modifications of nanoparticle surfaces by
      postfunctionalization approaches are less effective than in solution and often
      not high-yielding. In addition, the conjugation efficiency is often challenging
      to characterize and therefore not addressed in many reports. We present here an
      investigation of PEGylated liposomes functionalized with a neuroendocrine tumor
      targeting peptide (TATE), synthesized with a variety of functionalities that have
      been used for surface conjugation of nanoparticles. The reaction kinetics and
      overall yield were quantified by HPLC. Reactions were conducted in solution as
      well as by postfunctionalization of liposomes in order to study the effects of
      steric hindrance and possible affinity between the peptide and the liposome
      surface. These studies demonstrate the importance of choosing the correct
      chemistry in order to obtain a quantitative surface functionalization of
      liposomes.

PMID- 23153258
TI  - Helminth-infected patients with malaria: a low profile transmission hub?
AB  - Eclipsed by the debates about malaria incidence and severity in individual
      patients, malaria transmission in helminth-infected persons has so far received
      very little attention. Studies in humans have shown increased malaria incidence
      and prevalence, and a trend for a reduction of symptoms in patients with malaria.
      This suggests that such patients could possibly be less likely to seek treatment
      thus carrying malaria parasites and their gametocytes for longer durations,
      therefore, being a greater potential source of transmission. In addition, in
      humans, a study showed increased gametocyte carriage, and in an animal model of
      helminth-malaria co-infection, there was increased malaria transmission. These
      elements converge towards the hypothesis that patients co-infected with worms and
      malaria may represent a hub of malaria transmission. The test of this hypothesis
      requires verifying, in different epidemiological settings, that helminth-infected
      patients have more gametocytes, that they have less symptomatic malaria and
      longer-lasting infections, and that they are more attractive for the vectors. The
      negative outcome in one setting of one of the above aspects does not necessarily
      mean that the other two aspects may suffice to increase transmission. If it is
      verified that patients co-infected by worms and malaria could be a transmission
      hub, this would be an interesting piece of strategic information in the context
      of the spread of anti-malarial resistance and the malaria eradication attempts.

PMID- 23153259
TI  - Condom use at last sexual relationship among adolescents of Santiago Island, Cape
      Verde, - West Africa.
AB  - OBJECTIVE: To estimate factors associated with condom use at last sexual
      intercourse among adolescents. METHODS: Cross-sectional study of a representative
      sample of 368 sexually active adolescents aged 13-17 years from eight public high
      schools on Santiago Island, Cape Verde, 2007. The level of significance was 5.0%
      obtained from logistic regression, considering the association between condom use
      and socio-demographic, sexual and reproductive variables. RESULTS: The prevalence
      of condom use at last sexual intercourse was 94.9%. Factors associated with
      condom use at last sexual relationship were: non-Catholic religion (OR=0.68,
      95%CI: 0.52; 0.88) and affective-sexual partnership before the interview
      (OR=5.15, 95%CI: 1.79; 14.80). CONCLUSIONS: There was a high prevalence of condom
      use at last sexual intercourse of adolescents.

PMID- 23153260
TI  - Genetic diversity assessment of sesame core collection in China by phenotype and
      molecular markers and extraction of a mini-core collection.
AB  - BACKGROUND: Sesame (Sesamum indicum L.) is one of the four major oil crops in
      China. A sesame core collection (CC) was established in China in 2000, but no
      complete study on its genetic diversity has been carried out at either the
      phenotypic or molecular level. To provide technical guidance, a theoretical basis
      for further collection, effective protection, reasonable application, and a
      complete analysis of sesame genetic resources, a genetic diversity assessment of
      the sesame CC in China was conducted using phenotypic and molecular data and by
      extracting a sesame mini-core collection (MC). RESULTS: Results from a genetic
      diversity assessment of sesame CC in China were significantly inconsistent at the
      phenotypic and molecular levels. A Mantel test revealed the insignificant
      correlation between phenotype and molecular marker information (r = 0.0043, t =
      0.1320, P = 0.5525). The Shannon-Weaver diversity index (I) and Nei genetic
      diversity index (h) were higher (I = 0.9537, h = 0.5490) when calculated using
      phenotypic data from the CC than when using molecular data (I = 0.3467, h =
      0.2218). A mini-core collection (MC) containing 184 accessions was extracted
      based on both phenotypic and molecular data, with a low mean difference
      percentage (MD, 1.64%), low variance difference percentage (VD, 22.58%), large
      variable rate of coefficient of variance (VR, 114.86%), and large coincidence
      rate of range (CR, 95.76%). For molecular data, the diversity indices and the
      polymorphism information content (PIC) for the MC were significantly higher than
      for the CC. Compared to an alternative random sampling strategy, the advantages
      of capturing genetic diversity and validation by extracting a MC using an
      advanced maximization strategy were proven. CONCLUSIONS: This study provides a
      comprehensive characterization of the phenotypic and molecular genetic
      diversities of the sesame CC in China. A MC was extracted using both phenotypic
      and molecular data. Low MD% and VD%, and large VR% and CR% suggested that the MC
      provides a good representation of the genetic diversity of the original CC. The
      MC was more genetically diverse with higher diversity indices and a higher PIC
      value than the CC. A MC may aid in reasonably and efficiently selecting materials
      for sesame breeding and for genotypic biological studies, and may also be used as
      a population for association mapping in sesame.

PMID- 23153261
TI  - Women's experience of transfer from midwifery unit to hospital obstetric unit
      during labour: a qualitative interview study.
AB  - BACKGROUND: Midwifery units offer care to women with straightforward pregnancies,
      but unforeseen complications can arise during labour or soon after birth,
      necessitating transfer to a hospital obstetric unit. In England, 21% of women
      planning birth in freestanding midwifery units are transferred; in alongside
      units, the transfer rate is 26%. There is little high quality contemporary
      evidence on women's experience of transfer. METHODS: We carried out a qualitative
      interview study, using semi-structured interviews, with women who had been
      transferred from a midwifery unit (freestanding or alongside) in England up to 12
      months prior to interview. Maximum variation sampling was used. Interviews with
      30 women took place between March 2009 and March 2010. Thematic analysis using
      constant comparison and exploration of deviant cases was carried out. RESULTS:
      Most women hoped for or expected a natural birth and did not expect to be
      transferred. Transfer was disappointing for many; sensitive and supportive care
      and preparation for the need for transfer helped women adjust to their changing
      circumstances. A small number of women, often in the context of prolonged labour,
      described transfer as a relief. For women transferred from freestanding units,
      the ambulance journey was a "limbo" period. Women wondered, worried or were
      fearful about what was to come and could be passive participants who felt like
      they were being "transported" rather than cared for. For many this was a direct
      contrast with the care they experienced in the midwifery unit. After transfer,
      most women appreciated the opportunity to talk about their experience to make
      sense of what happened and help them plan for future pregnancies, but did not
      necessarily seek this out if it was not offered. CONCLUSIONS: Transfer affects a
      significant minority of women planning birth in midwifery units and is therefore
      a concern for women and midwives. Transfer is not expected by women, but
      sensitive care and preparation can help women adjust to changing circumstances.
      Particular sensitivity around decision-making may be required by midwives caring
      for women during prolonged labour. Some apparently straightforward changes to
      practice have the potential to make an important difference to women's experience
      of ambulance transfer.

PMID- 23153268
TI  - The development of mirror self-recognition in different sociocultural contexts.
AB  - The overarching goal of the present study was to trace the development of mirror
      self-recognition (MSR), as an index of toddlers' sense of themselves and others
      as autonomous intentional agents, in different sociocultural environments. A
      total of 276 toddlers participated in the present study. Toddlers were either 16,
      17, 18, 19, 20, or 21 months old at their first assessment and completed weekly
      MSR assessments over a period of 6 weeks (N = 1,577). The toddlers and their
      families were from one of four sociocultural contexts: A prototypical autonomous
      sociocultural context (urban German middle-class families, n = 82), two
      prototypical relational sociocultural contexts (rural Indian and rural Nso
      families living in subsistence-based ecologies, n = 54 and n = 80, respectively),
      or an autonomous-relational sociocultural context (urban Indian middle-class
      families, n = 60). In line with previous research, we hypothesized that the onset
      of MSR would be earlier in sociocultural contexts in which mothers value and
      support their toddlers' development of autonomy. In addition, we considered three
      factors that covary with culture and that might compromise the cross-cultural
      validity of MSR as a behavioral measure of toddlers' sense of themselves as
      independent agents: familiarity with mirrors, culture-specific norms of
      expressive behavior, and motivation for tactile exploration. Finally, we analyzed
      toddlers' reactions to their specular image (e.g., pointing, playmate, and
      experimenting behavior) across time and culture as well as their relation to MSR.
      The results indicate that MSR increased with age in all sociocultural contexts.
      In line with our hypotheses, MSR rates were higher in the autonomy-supporting
      cultural context (urban German, urban Indian) than they were in the relational
      cultural contexts(rural Indian, rural Nso). The sociocultural differences in MSR
      could not, however, be explained by differences in mirror familiarity or culture
      specific norms of expressive behavior. The cross-cultural validity of MSR as an
      index of toddlers' sense of themselves as independent agents is further supported
      by positive associations between MSR and pronoun use in all sociocultural
      contexts. Cross-cultural variation in MSR could best be explained by caretakers'
      emphasis on autonomous socialization goals, followed by toddlers' motivation for
      tactile exploration. These findings enhance our current understanding of
      development in more general terms by adding one more puzzle piece to the emerging
      picture of culture-specific developmental pathways. In order to understand
      developmental processes, one must take into account caretakers' cultural models
      and exercise caution when generalizing beyond the specific sociocultural context
      at hand.

PMID- 23153270
TI  - Exploring the pathophysiology of hypogonadism in men with type 2 diabetes:
      kisspeptin-10 stimulates serum testosterone and LH secretion in men with type 2
      diabetes and mild biochemical hypogonadism.
AB  - RATIONALE: Low serum testosterone is commonly observed in men with type 2
      diabetes (T2DM), but the neuroendocrine pathophysiology remains to be elucidated.
      OBJECTIVES: The hypothalamic neuropeptide kisspeptin integrates metabolic signals
      with the reproductive axis in animal models. We hypothesized that administration
      of exogenous kisspeptin-10 will restore luteinizing hormone (LH) and testosterone
      secretion in hypotestosteronaemic men with T2DM. PARTICIPANTS: Five
      hypotestosteronaemic men with T2DM (age 33.6 +/- 3 years, BMI 40.6 +/- 6.3, total
      testosterone 8.5 +/- 1.0 nmol/l, LH 4.7 +/- 0.7 IU/l, HbA1c 7.4+/-2%, duration of
      diabetes <5 years) and seven age-matched healthy men. EXPERIMENT 1: Mean LH
      increased in response to intravenous administration of kisspeptin-10 (0.3 mcg/kg
      bolus) both in healthy men (5.5 +/- 0.8 to 13.9 +/- 1.7 IU/l P < 0.001) and in
      men with T2DM (4.7 +/- 0.7 to 10.7 +/- 1.2 IU/l P = 0.02) with comparable DeltaLH
      (P = 0.18). EXPERIMENT 2: Baseline 10-min serum sampling for LH and hourly
      testosterone measurements were performed in four T2DM men over 12 h. An
      intravenous infusion of kisspeptin-10 (4 mcg/kg/h) was administered for 11 h, 5
      days later. There were increases in LH (3.9 +/- 0.1 IU/l to 20.7 +/- 1.1 IU/l P =
      0.03) and testosterone (8.5 +/- 1.0 to 11.4 +/- 0.9 nmol/l, P = 0.002). LH pulse
      frequency increased from 0.6 +/- 0.1 to 0.9 +/- 0 pulses/h (P = 0.05) and
      pulsatile component of LH secretion from 32.1 +/- 8.0 IU/l to 140.2 +/- 23.0 IU/l
      (P = 0.007). CONCLUSIONS: Kisspeptin-10 administration increased LH pulse
      frequency and LH secretion in hypotestosteronaemic men with T2DM in this proof-of
      concept study, with associated increases in serum testosterone. These data
      suggest a potential novel therapeutic role for kisspeptin agonists in enhancing
      endogenous testosterone secretion in men with T2DM and central hypogonadism.

PMID- 23153271
TI  - Simple method for confirming tibial osteotomy during total knee arthroplasty.
AB  - BACKGROUND: Achieving precise implant alignment is crucial for producing good
      outcomes after total knee arthroplasty (TKA). We introduce a simple method for
      confirming the accuracy of tibial osteotomy during TKA. FINDINGS: Two metallic
      markers were placed on the skin 20 cm apart, one on the tibial tuberosity and
      other on the tibial crest, points that are easily identified and palpated
      intraoperatively. Anteroposterior radiographs of the legs were obtained. We
      defined the line along the markers as the tuberosity line. The osteotomy line is
      perpendicular to the anatomical axis of the tibia. We then calculated the angle
      between these two lines and designated it the osteotomy angle. We set the
      osteotomy angle of the protractor, and cut the bone parallel to the osteotomy
      line of the protractor. Postoperatively, we analyzed the varus angle of the
      tibial osteotomy in 35 TKAs using the protractor. The average of the varus angle
      of the tibial osteotomy was 89.4 degrees  +/- 1.6 degrees  (95% confidence
      interval of -1.0976, 0.0119). There was no significant difference from the target
      angle of 90 degrees  (p = 0.055). The varus angles of 90 degrees  and 90 degrees 
      +/- 2 degrees  for the tibial osteotomy were 42.9% and 82.9%, respectively.
      CONCLUSIONS: We determined the accuracy of the tibial osteotomy in the coronal
      plane using the protractor to be satisfactory.

PMID- 23153272
TI  - Thermodynamic and kinetic controls on cotransport of Pantoea agglomerans cells
      and Zn through clean and iron oxide coated sand columns.
AB  - Recent observations that subsurface bacteria quickly adsorb metal contaminants
      raise concerns that they may enhance metal transport, given the high mobility of
      bacteria themselves. However, metal adsorption to bacteria is also reversible,
      suggesting that mobility within porous medium will depend on the interplay
      between adsorption-desorption kinetics and thermodynamic driving forces for
      adsorption. Till now there has been no systematic investigation of these
      important interactions. This study investigates the thermodynamic and kinetic
      controls of cotransport of Pantoea agglomerans cells and Zn in quartz and iron
      oxide coated sand (IOCS) packed columns. Batch kinetic studies show that
      significant Zn sorption on IOCS takes place within two hours. Adsorption onto P.
      agglomerans surfaces reaches equilibrium within 30 min. Experiments in flow
      through quartz sand systems demonstrate that bacteria have negligible effect on
      zinc mobility, regardless of ionic strength and pH conditions. Zinc transport
      exhibits significant retardation in IOCS columns at high pH in the absence of
      cells. Yet, when mobile bacteria (non attached) are passed through simultaneously
      with zinc, no facilitated transport is observed. Adsorption onto cells becomes
      significant and plays a role in mobile metal speciation only once the IOCS is
      saturated with zinc. This suggests that IOCS exhibits stronger affinity for Zn
      than cell surfaces. However, when bacteria and Zn are preassociated on entering
      the column, zinc transport is initially facilitated. Subsequently, zinc partly
      desorbs from the cells and redistributes onto the IOCS as a result of the higher
      thermodynamic affinity for IOCS.

PMID- 23153274
TI  - Expanding the scope of donor/acceptor carbenes to N-phthalimido donor groups:
      diastereoselective synthesis of 1-cyclopropane alpha-amino acids.
AB  - Warming of 4-phthalimido-N-mesyl-1,2,3-triazole in the presence of alkenes
      followed by silica gel induced hydrolysis results in a highly diastereoselective
      and catalyst-free entry to N-phthalimidocyclopropanecarboxaldehydes.

PMID- 23153275
TI  - Mapping molecular perturbations by a new form of two-dimensional spectroscopy.
AB  - We propose a new general form of two-dimensional spectroscopy where the indirect
      "evolution" dimension is derived using the Radon transform. This idea is
      applicable to several types of spectroscopy but is illustrated here for the case
      of NMR spectroscopy. This "projection spectroscopy" displays characteristic
      correlation peaks that highlight perturbations of chemical shifts caused by
      temperature, pressure, solvent, molecular binding, chemical exchange, hydrogen
      bonding, pH variations, conformational changes, or paramagnetic agents. The
      results are displayed in a convenient format that allows the chemist to see all
      of the chemical shift perturbations at a glance and assess their rates of change
      and directions. As a proof of principle, we present two simple, practical
      examples that display two-dimensional representations of the effects of
      temperature and solvent on NMR spectra.

PMID- 23153273
TI  - General anesthesia and human brain connectivity.
AB  - General anesthesia consists of amnesia, hypnosis, analgesia, and areflexia. Of
      these, the mechanism of hypnosis, or loss of consciousness, has been the most
      elusive, yet a fascinating problem. How anesthetic agents suppress human
      consciousness has been investigated with neuroimaging for two decades.
      Anesthetics substantially reduce the global cerebral metabolic rate and blood
      flow with a degree of regional heterogeneity characteristic to the anesthetic
      agent. The thalamus appears to be a common site of modulation by several
      anesthetics, but this may be secondary to cortical effects. Stimulus-dependent
      brain activation is preserved in primary sensory areas, suggesting that
      unconsciousness cannot be explained by cortical deafferentation or a diminution
      of cortical sensory reactivity. The effect of general anesthetics in functional
      and effective connectivity is varied depending on the agent, dose, and network
      studied. At an anesthetic depth characterized by the subjects' unresponsiveness,
      a partial, but not complete, reduction in connectivity is generally observed.
      Functional connectivity of the frontoparietal association cortex is often
      reduced, but a causal role of this change for the loss of consciousness remains
      uncertain. Functional connectivity of the nonspecific (intralaminar) thalamic
      nuclei is preferentially reduced by propofol. Higher-order thalamocortical
      connectivity is also reduced with certain anesthetics. The changes in functional
      connectivity during anesthesia induction and emergence do not mirror each other;
      the recovery from anesthesia may involve increases in functional connectivity
      above the normal wakeful baseline. Anesthetic loss of consciousness is not a
      block of corticofugal information transfer, but a disruption of higher-order
      cortical information integration. The prime candidates for functional networks of
      the forebrain that play a critical role in maintaining the state of consciousness
      are those based on the posterior parietal-cingulate-precuneus region and the
      nonspecific thalamus.

PMID- 23153276
TI  - Association between 24-hour urine sodium and potassium excretion and diet quality
      in six-year-old children: a cross sectional study.
AB  - BACKGROUND: Limited data is available on sodium (Na) and potassium (K) intake in
      young children estimated by 24 hour (24h) excretion in urine. The aim was to
      assess 24h urinary excretion of Na and K in six-year-old children and its
      relationship with diet quality. METHODS: The study population was a subsample of
      a national dietary survey, including six-year-old children living in the greater
      Reykjavik area (n=76). Three day weighed food records were used to estimate diet
      quality. Diet quality was defined as adherence to the Icelandic food based
      dietary guidelines. Na and K excretion was analyzed from 24h urine collections.
      PABA check was used to validate completeness of urine collections. The
      associations between Na and K excretion and diet quality were estimated by linear
      regression, adjusting for gender and energy intake. RESULTS: Valid urine
      collections and diet registrations were provided by 58 children. Na and K
      excretion was, mean (SD), 1.64 (0.54) g Na/24h (approx. 4.1 g salt/24h) and 1.22
      (0.43) g K/24h. In covariate adjusted models Na excretion decreased by 0.16 g
      Na/24h (95% CI: 0.31, 0.06) per 1-unit increase in diet quality score (score
      range: 1-4) while K excretion was increased by 0.18 g K/24h (95% CI: 0.06, 0.29).
      CONCLUSIONS: Na intake, estimated by 24h urinary excretion was on average higher
      than recommended. Increased diet quality was associated with lower Na excretion
      and higher K excretion in six-year-old children.

PMID- 23153278
TI  - Thermodynamic study on dynamic water vapor sorption in Sylgard-184.
AB  - The dynamic and equilibrium water vapor sorption properties of Sylgard-184, a
      commercially available poly(dimethylsiloxane) elastomer (PDMS), were determined
      via gravimetric analysis from 30 to 70  degrees C. Described here is a
      methodology for quantitatively assessing how water vapor diffuses and ad/absorbs
      into polymeric materials that are traditionally considered hydrophobic. PDMS
      materials are frequently chosen for their moisture barrier properties; our
      results, however, demonstrate that moisture is able to penetrate the material
      over a range of temperatures and humidities. The sorption values measured here
      ranged from ca. 0.1 to 1.4 cm(3) (STP) H(2)O/g Sylgard. The isotherms exhibited
      sigmoidal character and were fit to a triple mode sorption model. Asymptotic
      behavior at low water activities was characterized using a Langmuir type
      adsorption model, linear behavior was fit to a Henry's law type dependence, and
      the convex portion at higher activities was fit with good agreement to Park's
      equation for pooling or clustering. The thermal dependence of these sorption
      modes was also explored and reported. The dynamics of the sorption process were
      fit to a Fickian model and effective diffusivities are reported along with
      corresponding activation energies. The diffusivity values measured here ranged
      from ca. 0.5 to 3.5 * 10(-5) cm(2)/s depending on the temperature and relative
      humidity. The concentration dependence of the diffusivity showed a direct
      correlation with the three modes of uptake obtained from the isotherms.
      Corrections to the diffusivities were calculated using existing models that take
      into account adsorption and pooling.

PMID- 23153277
TI  - Co-expression analysis identifies putative targets for CBP60g and SARD1
      regulation.
AB  - BACKGROUND: Salicylic acid is a critical signalling component in plant defence
      responses. In Arabidopsis, isochorismate synthase encoded by SID2 is essential
      for the biosynthesis of salicylic acid in response to biotic challenges.
      Recently, both the calmodulin binding protein CBP60g and its closest homolog, the
      non-calmodulin binding SARD1, have been shown to bind to the promoter region of
      SID2. Loss of both CBP60g and SARD1 severely impacts the plants ability to
      produce SA in response to bacterial inoculation and renders the plant susceptible
      to infection. In an electrophoretic mobility shift assay CBP60g and SARD1 were
      shown to bind specifically to a 10mer oligonucleotide with the sequence
      GAAATTTTGG. RESULTS: Gene expression profiling on a custom microarray identified
      a set of genes, like SID2, down-regulated in cbp60g sard1 mutant plants. Co
      expression analysis across a defined set of ATH1 full genome microarray
      experiments expanded this gene set; clustering analysis was then applied to group
      densely interconnected genes. A stringent threshold for co-expression identified
      two related calmodulin-like genes tightly associated with SID2. SID2 was found to
      cluster with genes whose promoter regions were significantly enriched with GAAATT
      motifs. Genes clustering with SID2 were found to be down-regulated in the cbp60g
      sard1 double mutant. Representative genes from other clusters enriched with the
      GAAATT motif were found to be variously down-regulated, unchanged or up-regulated
      in the double mutant. A previously characterised co-expression between SID2 and
      WRKY28 was not reproduced in this analysis but was contained within a subset of
      the experiments where SID2 was co-expressed with CBP60g or SARD1. CONCLUSION:
      Putative components of the CBP60g SARD1 signalling network have been uncovered by
      co-expression analysis. In addition to genes whose regulation is similar to that
      of SID2 some are repressed by CBP60g and SARD1.

PMID- 23153281
TI  - Mechanism of CO displacement from an unusually labile rhenium complex: an
      experimental and theoretical investigation.
AB  - The displacement of a CO ligand from an unusually labile rhenium carbonyl complex
      containing a bidentate carboxyaldehyde pyrrolyl ligand by PPh(3) and pyridine has
      been investigated. The reaction is found to proceed by an associative,
      preequilibrium mechanism. Theoretical calculations support the experimental data
      and provide a complete energetic profile for the reaction. While the Re-CO bond
      is found to be intrinsically weak in these complexes, it is postulated that the
      unusual lability of this species is due to the presence of a weak aldehyde Re-O
      link that can easily dissociate to open a coordination site on the metal center
      and accommodate an incoming ligand prior to CO loss. The resulting intermediate
      complex has been identified by IR spectroscopy. The presence of the hemilabile
      pyrrolyl ligand provides a lower-energy reaction channel for the release of CO
      and may be of relevance in the design of CO-releasing molecules.

PMID- 23153280
TI  - Endothelial nitric oxide synthase, vascular integrity and human exceptional
      longevity.
AB  - Aging is the sum of the deleterious changes that occur as time goes by. It is
      the main risk factor for the development of cardiovascular disease, and aging of
      the vasculature is the event that most often impacts on the health of elderly
      people. The "free-radical theory of aging" was proposed to explain aging as a
      consequence of the accumulation of reactive oxygen species (ROS). However, recent
      findings contradict this theory, and it now seems that mechanisms mediating
      longevity act through induction of oxidative stress. In fact, calorie restriction
      - a powerful way of delaying aging - increases ROS accumulation due to
      stimulation of the basal metabolic rate; moreover, reports show that antioxidant
      therapy is detrimental to healthy aging. We also now know that genetic
      manipulation of the insulin-like-growth-factor-1/insulin signal (IIS) has a
      profound impact on the rate of aging and that the IIS is modulated by calorie
      restriction and physical exercise. The IIS regulates activation of nitric oxide
      synthase (eNOS), the activity of which is essential to improving lifespan through
      calorie restriction, as demonstrated by experiments on eNOS knockout mice.
      Indeed, eNOS has a key role in maintaining vascular integrity during aging by
      activating vasorelaxation and allowing migration and angiogenesis. In this
      review, we will overview current literature on these topics and we will try to
      convince the reader of the importance of vascular integrity and nitric oxide
      production in determining healthy aging.

PMID- 23153282
TI  - Synthesis of new 7-oxycoumarin derivatives as potent and selective monoamine
      oxidase A inhibitors.
AB  - New series of 4-methyl and 3,4-dimethyl-7-oxycoumarin derivatives (oxadiazoles,
      thiadiazoles, triazoles, and thiazolidinones) were designed, synthesized, and
      evaluated for their monoamine oxidase (MAO) A and B inhibiting effect. All the
      synthesized compounds showed in vitro high affinity and selectivity toward MAO-A
      isoenzyme, compared to clorgyline and moclobemide, with Ki values on the
      picomolar range. Moreover, most of the tested compounds displayed MAO inhibitory
      effect when tested in vivo. The docking experiments carried out on MAO-A and MAO
      B structures proved new information about the enzyme-inhibitor interaction and
      the potential therapeutic application of 7-oxycoumarin scaffold.

PMID- 23153284
TI  - Fearful faces grab attention in the absence of late affective cortical responses.
AB  - Previous studies utilizing the N2pc, an ERP correlate of attentional focusing,
      demonstrated that fearful faces grab attention regardless of their relevance to
      the current task. We tested whether this apparent automaticity was susceptible to
      high concurrent task demand, which is known to suppress other cortical and
      subcortical emotional evaluations. Our data revealed that the affective
      attentional capture occurred even under high task load, by which the late
      cortical affective activity (the LPP modulation) was entirely suppressed. We also
      confirmed that this effect did not occur to inverted faces and therefore required
      a holistic perception of facial expression. These results show that, given an
      intact processing of facial expression, attention is attracted by fearful faces
      in a relatively automatic fashion as compared to other cortical affective
      processes.

PMID- 23153283
TI  - Piper betle shows antioxidant activities, inhibits MCF-7 cell proliferation and
      increases activities of catalase and superoxide dismutase.
AB  - BACKGROUND: Breast cancer is the most common form of cancer and the focus on
      finding chemotherapeutic agents have recently shifted to natural products. Piper
      betle is a medicinal plant with various biological activities. However, not much
      data is available on the anti-cancer effects of P. betle on breast cancer. Due to
      the current interest in the potential effects of antioxidants from natural
      products in breast cancer treatment, we investigated the antioxidant activities
      of the leaves of P. betle and its inhibitory effect on the proliferation of the
      breast cancer cell line, MCF-7. METHODS: The leaves of P. betle were extracted
      with solvents of varying polarities (water, methanol, ethyl acetate and hexane)
      and their phenolic and flavonoid content were determined using colorimetric
      assays. Phenolic composition was characterized using HPLC. Antioxidant activities
      were measured using FRAP, DPPH, superoxide anion, nitric oxide and hyroxyl
      radical scavenging assays. Biological activities of the extracts were analysed
      using MTT assay and antioxidant enzyme (catalase, superoxide dismutase,
      glutathione peroxidase) assays in MCF-7 cells. RESULTS: Overall, the ethyl
      acetate extract showed the highest ferric reducing activity and radical
      scavenging activities against DPPH, superoxide anion and nitric oxide radicals.
      This extract also contained the highest phenolic content implying the potential
      contribution of phenolics towards the antioxidant activities. HPLC analyses
      revealed the presence of catechin, morin and quercetin in the leaves. The ethyl
      acetate extract also showed the highest inhibitory effect against the
      proliferation of MCF-7 cells (IC50=65 MUg/ml). Treatment of MCF-7 cells with the
      plant extract increased activities of catalase and superoxide dismutase.
      CONCLUSIONS: Ethyl acetate is the optimal solvent for the extraction of compounds
      with antioxidant and anti-proliferative activities. The increased activities of
      catalase and superoxide dismutase in the treated cells could alter the
      antioxidant defense system, potentially contributing towards the anti
      proliferative effect. There is great potential for the ethyl acetate extract of
      P. betle leaf as a source of natural antioxidants and to be developed as
      therapeutics in cancer treatment.

PMID- 23153285
TI  - A de novo germline mutation in MYH7 causes a progressive dominant myopathy in
      pigs.
AB  - BACKGROUND: About 9% of the offspring of a clinically healthy Pietrain boar named
      'Campus' showed a progressive postural tremor called Campus syndrome (CPS).
      Extensive backcross experiments suggested a dominant mode of inheritance, and the
      founder boar was believed to be a gonadal mosaic. A genome-scan mapped the
      disease-causing mutation to an 8 cM region of porcine chromosome 7 containing the
      MHY7 gene. Human distal myopathy type 1 (MPD1), a disease partially resembling
      CPS in pigs, has been associated with mutations in the MYH7 gene. RESULTS: The
      porcine MYH7 gene structure was predicted based on porcine reference genome
      sequence, porcine mRNA, and in comparison to the human ortholog. The gene
      structure was highly conserved with the exception of the first exon. Mutation
      analysis of a contiguous genomic interval of more than 22 kb spanning the
      complete MYH7 gene revealed an in-frame insertion within exon 30 of MYH7
      (c.4320_4321insCCCGCC) which was perfectly associated with the disease phenotype
      and confirmed the dominant inheritance. The mutation is predicted to insert two
      amino acids (p.Ala1440_Ala1441insProAla) in a very highly conserved region of the
      myosin tail. The boar 'Campus' was shown to be a germline and somatic mosaic as
      assessed by the presence of the mutant allele in seven different organs.
      CONCLUSION: This study illustrates the usefulness of recently established genomic
      resources in pigs. We have identified a spontaneous mutation in MYH7 as the
      causative mutation for CPS. This paper describes the first case of a disorder
      caused by a naturally occurring mutation in the MYH7 gene of a non-human
      mammalian species. Our study confirms the previous classification as a primary
      myopathy and provides a defined large animal model for human MPD1. We provide
      evidence that the CPS mutation occurred during the early development of the boar
      'Campus'. Therefore, this study provides an example of germline mosaicism with an
      asymptomatic founder.

PMID- 23153286
TI  - Food safety systems in a small dairy factory: implementation, major challenges,
      and assessment of systems' performances.
AB  - The present study describes the implementation of a food safety system in a dairy
      processing plant located in the State of Sao Paulo, Brazil, and the challenges
      found during the process. In addition, microbiological indicators have been used
      to assess system's implementation performance. The steps involved in the
      implementation of a food safety system included a diagnosis of the prerequisites,
      implementation of the good manufacturing practices (GMPs), sanitation standard
      operating procedures (SSOPs), training of the food handlers, and hazard analysis
      and critical control point (HACCP). In the initial diagnosis, conformity with
      70.7% (n=106) of the items analyzed was observed. A total of 12 critical control
      points (CCPs) were identified: (1) reception of the raw milk, (2) storage of the
      raw milk, (3 and 4) reception of the ingredients and packaging, (5) milk
      pasteurization, (6 and 7) fermentation and cooling, (8) addition of ingredients,
      (9) filling, (10) storage of the finished product, (11) dispatching of the
      product, and (12) sanitization of the equipment. After implementation of the food
      safety system, a significant reduction in the yeast and mold count was observed
      (p<0.05). The main difficulties encountered for the implementation of food safety
      system were related to the implementation of actions established in the flow
      chart and to the need for constant training/adherence of the workers to the
      system. Despite this, the implementation of the food safety system was shown to
      be challenging, but feasible to be reached by small-scale food industries.

PMID- 23153287
TI  - Spatial distribution of the emerging foodborne pathogen Arcobacter in the
      gastrointestinal tract of pigs.
AB  - Pigs are important reservoirs for Arcobacter. Since 1978, Arcobacter species have
      been associated with reproduction disorders, but excretion by clinically healthy
      pigs has been frequently reported as well. Information on Arcobacter colonization
      of the porcine gastrointestinal tract is lacking. In the present study,
      gastrointestinal tracts of 12 pigs were collected, and the content and mucus of
      eight sections were examined. Arcobacters were enumerated and isolated by a
      selective quantitative and qualitative method, respectively, and identified by
      multiplex-polymerase chain reaction (PCR). Their genetic diversity was examined
      by enterobacterial repetitive intergenic consensus PCR and pulsed-field gel
      electrophoresis. Arcobacter species were isolated from at least two
      gastrointestinal sections of all pigs in levels up to 10(5) colony-forming units
      (CFU) g(-1) in content and 10(4) CFU g(-1) in mucus. Characterization of the
      isolates revealed a high degree of genotypic diversity. In general, the highest
      counts, and greatest species and strain diversity was obtained from the large
      intestine, and especially from the rectum. Though Arcobacter strains were mostly
      detected in one gastrointestinal section, several unique strains were also
      recovered from the content and/or mucus of various gastrointestinal sections of
      individual pigs. In the gastrointestinal tract, Arcobacter is present with
      species distributions, numbers, and strain heterogeneity comparable to those
      reported on porcine carcasses post slaughter, thus confirming the potential route
      of transmission to carcasses by fecal contamination during processing.

PMID- 23153288
TI  - Sequencing of virulence genes shows limited genetic variability in Yersinia
      pseudotuberculosis.
AB  - Yersinia pseudotuberculosis is a foodborne pathogen often detected and identified
      using polymerase chain reaction (PCR) with primers targeted to virulence genes.
      Sequence variability of the virulence genes in strains representing different
      serotypes is unknown. Sequence variability could hinder the recognition of this
      pathogen by PCR and affect the host-pathogen interactions. Sequencing of inv,
      virF, and yadA of 18 Y. pseudotuberculosis strains showed limited variability of
      inv and virF, whereas the sequences of yadA varied considerably.

PMID- 23153290
TI  - Theoretical investigations toward the [4 + 2] cycloaddition of ketenes with N
      benzoyldiazenes catalyzed by N-heterocyclic carbenes: mechanism and
      enantioselectivity.
AB  - Density functional theory (DFT) calculations have been performed to provide the
      first detailed computational study on the mechanism and enantioselectivity for
      the [4 + 2] cycloaddition reaction of ketenes with N-benzoyldiazenes catalyzed by
      N-heterocyclic carbenes (NHCs). Two possible mechanisms have been studied: first
      is the "ketene-first" mechanism (mechanism A), and second is the novel "diazene
      first" mechanism (mechanism B). The calculated results reveal that mechanism B is
      more favorable than mechanism A because it is not only of lower energy barrier
      but also more consistent with the provided general experimental procedure (Huang,
      X.-L.; He, L.; Shao, P.-L.; Ye, S. Angew. Chem., Int. Ed.2009, 48, 192-195). The
      enantioselectivity-determining step is demonstrated to present during the first
      process of cycloaddition, and the main product configuration is verified to agree
      with the experimental ee values very well. This study should be of some worth on
      forecasting how different substituent groups of catalysts and/or reactants affect
      the enantioselectivity of products. The obtained novel mechanistic insights
      should be valuable for not only rational design of more efficient NHC catalysts
      but also understanding the general reaction mechanism of [4 + 2] cycloaddition of
      ketenes.

PMID- 23153289
TI  - Waist circumference and pulmonary function: a systematic review and meta
      analysis.
AB  - BACKGROUND: Studies have reported an impact of central obesity on people's
      health. The literature is scarce on the effects of waist circumference (WC) on
      pulmonary function. Our objective was to review the literature on the association
      between WC and pulmonary function. METHODS: A systematic review was carried out
      in the PubMed, CINAHL, Web of Science and Scopus databases. The search included
      published, in press and online documents up to December 2011. A meta-analysis was
      carried out to obtain the pooled effect, and a meta-regression was performed to
      evaluate sources of heterogeneity. RESULTS: From the 547 studies identified, 10
      were included. The meta-analysis revealed an inverse relationship between WC and
      pulmonary function parameters, indicating that the effect was greater among men
      (forced expiratory volume in 1 second (FEV1 beta = -15.9 (95% confidence interval
      = -23.2, -8.5); forced vital capacity (FVC) beta = -16.6 (95% confidence interval
      = -21.0, -12.2)) compared with women (FEV1 beta = -5.6 (95% confidence interval =
      -9.1, -2.1); FVC beta = -7.0 (95% confidence interval = -9.1, -4.8)). The meta
      regression identified sex as the characteristic that most contributed to the
      heterogeneity (R2 = 54.8% for FEV1 and R2 = 85.7% for FVC). CONCLUSIONS: There
      seems to be an inverse relationship between WC and pulmonary function, mainly in
      men. More population-based studies should be performed, especially among children
      and adolescents, to confirm these findings.

PMID- 23153291
TI  - Low-level laser therapy for treatment of pain associated with orthodontic
      elastomeric separator placement: a placebo-controlled randomized double-blind
      clinical trial.
AB  - OBJECTIVE: The objective of this study was to evaluate the effectiveness of the
      use of irradiation with a low-level laser therapy (LLLT), wavelength 830 nm, for
      treating pain inherent to tooth movement caused by orthodontic devices, simulated
      by positioning interdental elastomeric separators. METHODS: Sixty orthodontic
      patients were randomly assigned to two groups: GA (ages 12-25 years; mean 17.1
      years) was the control, and GB (ages 12-26 years; mean 17.9 years) the
      intervention group. All patients received elastomeric separators on the mesial
      and distal surfaces of one of the lower first molars, and immediately after
      insertion of the separators received irradiation as randomly indicated. The
      intervention group (GB) received irradiation with LLLT (aluminum gallium arsenide
      diode), by a single spot in the region of the radicular apex at a dose of 2
      J/cm(2) and application along the radicular axis of the buccal surface with three
      spots of 1 J/cm(2) (wavelength 830 nm; infrared). Control group (GA) received
      irradiation with a placebo light in the same way. This was a double-blind study.
      All the patients received a questionnaire to be filled out at home describing
      their levels of pain 2, 6, and 24 h and 3 and 5 days after orthodontic separator
      placement, in situations of relaxed and occluded mouth. RESULTS: The patients in
      the intervention group (LLLT) had lower mean pain scores in all the measures. The
      incidence of complete absence of pain (score=0) was significantly higher the
      intervention group. CONCLUSIONS: Based on this study, authors concluded that
      single irradiation with LLLT of wavelength 830 nm efficiently controlled the pain
      originating from positioning interdental elastomeric separators, to reproduce the
      painful sensation experienced by patients when fixed orthodontic devices are
      used.

PMID- 23153293
TI  - Disturbance in melatonin metabolism as a causative factor for recurrent headaches
      in a girl with a pineal cyst?

PMID- 23153292
TI  - Spatial morphological and molecular differences within solid tumors may
      contribute to the failure of vascular disruptive agent treatments.
AB  - BACKGROUND: Treatment of solid tumors with vascular disrupting agent OXi4503
      results in over 90% tumor destruction. However, a thin rim of viable cells
      persists in the tumor periphery following treatment, contributing to subsequent
      recurrence. This study investigates inherent differences in the microenvironment
      of the tumor periphery that contribute to treatment resistance. METHODS: Using a
      murine colorectal liver metastases model, spatial morphological and molecular
      differences within the periphery and the center of the tumor that may account for
      differences in resistance to OXi4503 treatment were investigated. H&E staining
      and immunostaining were used to examine vessel maturity and stability, hypoxia
      and HIF1alpha levels, accumulation of immune cells, expression of proangiogenic
      factors/receptors (VEGF, TGF-beta, b-FGF, and AT1R) and expression of EMT markers
      (ZEB1, vimentin, E-cadherin and beta-catenin) in the periphery and center of
      established tumors. The effects of OXi4503 on tumor vessels and cell kinetics
      were also investigated. RESULTS: Significant differences were found between tumor
      periphery and central regions, including association of the periphery with mature
      vessels, higher accumulation of immune cells, increased growth factor expression,
      minimal levels of hypoxia and increased evidence of EMT. OXi4503 treatment
      resulted in collapse of vessels in the tumor center; however vasculature in the
      periphery remained patent. Similarly, tumor apoptosis and proliferation were
      differentially modulated between centre and periphery after treatment.
      CONCLUSIONS: The molecular and morphological differences between tumor periphery
      and center may account for the observed differential resistance to OXi4503
      treatment and could provide targets for drug development to totally eliminate
      metastases.

PMID- 23153294
TI  - Causes of crises and appropriate interventions: the views of people with
      dementia, carers and healthcare professionals.
AB  - The aims of this study were to identify which factors may lead to crisis for
      people with dementia and their carers and identify interventions these
      individuals believe could help in crisis. Qualitative study using focus groups to
      compare the perspectives of people with dementia, family carers and healthcare
      professionals on causes of crises and crisis interventions. To help in a crisis,
      people with dementia were favourable towards support from family and friends,
      access to mobile phones and home adaptations to reduce risks. Carers were keen on
      assistive technology and home adaptation. Both carers and staff valued carer
      training and education, care plans and well-coordinated care. Staff were the only
      group emphasizing more intensive interventions such as emergency home respite and
      extended hours services. In terms of causes of crises, people with dementia
      focused on risks and hazards in their home, whereas family carers emphasized
      carer stress and their own mental health problems. Staff, in contrast were
      concerned about problems with service organization and coordination leading to
      crises. Physical problems were less commonly identified as causes of crises but
      when they did occur they had a major impact. Practical interventions such as home
      adaptations, assistive technology, education and training for family carers, and
      flexible home care services were highly valued by service users and their
      families during times of crisis and may help prevent hospital admissions.
      Specialist home care was highly valued by all groups.

PMID- 23153299
TI  - Ultrafast excited-state intramolecular proton transfer of aloesaponarin I.
AB  - Time-resolved emission of aloesaponarin I was studied with the fluorescence up
      conversion and time-correlated single-photon-counting techniques. The rates of
      the excited-state intramolecular proton transfer, of the solvent and molecular
      rearrangements, and of the decay from the excited proton-transferred species were
      determined and interpreted in the light of time-dependent density functional
      calculations. These results were discussed in conjunction with UV protection and
      singlet-oxygen quenching activity of aloe.

PMID- 23153298
TI  - Stress inducible proteinase inhibitor diversity in Capsicum annuum.
AB  - BACKGROUND: Wound-inducible Pin-II Proteinase inhibitors (PIs) are one of the
      important plant serine PIs which have been studied extensively for their
      structural and functional diversity and relevance in plant defense against insect
      pests. To explore the functional specialization of an array of Capsicum annuum
      (L.) proteinase inhibitor (CanPIs) genes, we studied their expression, processing
      and tissue-specific distribution under steady-state and induced conditions.
      Inductions were performed by subjecting C. annuum leaves to various treatments,
      namely aphid infestation or mechanical wounding followed by treatment with either
      oral secretion (OS) of Helicoverpa armigera or water. RESULTS: The elicitation
      treatments regulated the accumulation of CanPIs corresponding to 4-, 3-, and 2
      inhibitory repeat domains (IRDs). Fourty seven different CanPI genes composed of
      28 unique IRDs were identified in total along with those reported earlier. The
      CanPI gene pool either from uninduced or induced leaves was dominated by 3-IRD
      PIs and trypsin inhibitory domains. Also a major contribution by 4-IRD CanPI
      genes possessing trypsin and chymotrypsin inhibitor domains was specifically
      revealed in wounded leaves treated with OS. Wounding displayed the highest number
      of unique CanPIs while wounding with OS treatment resulted in the high
      accumulation of specifically CanPI-4, -7 and -10. Characterization of the PI
      protein activity through two dimensional gel electrophoresis revealed tissue and
      induction specific patterns. Consistent with transcript abundance, wound plus OS
      or water treated C. annuum leaves exhibited significantly higher PI activity and
      isoform diversity contributed by 3- and 4-IRD CanPIs. CanPI accumulation and
      activity was weakly elicited by aphid infestation yet resulted in the higher
      expression of CanPI-26, -41 and -43. CONCLUSIONS: Plants can differentially
      perceive various kinds of insect attacks and respond appropriately through
      activating plant defenses including regulation of PIs at transcriptional and post
      translational levels. Based on the differentially elicited CanPI accumulation
      patterns, it is intriguing to speculate that generating sequence diversity in the
      form of multi-IRD PIs is a part of elaborative plant defense strategy to obtain a
      diverse pool of functional units to confine insect attack.

PMID- 23153300
TI  - Cell-based reporter gene assay for therapy-induced neutralizing antibodies to
      interferon-beta in multiple sclerosis.
AB  - Patients with therapy-induced neutralizing antibodies (NAbs) to interferon-beta
      (IFN-beta) have reduced responses to IFN-beta treatment, resulting in higher
      relapse rates, increased magnetic resonance imaging activity, and a higher risk
      of disease progression. A functional assay was employed for both screening and
      titering of IFN-beta NAbs utilizing a human cell line transfected with a
      luciferase reporter gene responsive to IFN-beta. This assay demonstrated 100%
      sensitivity and specificity compared with the traditional cytopathic effect (CPE)
      assay and normal donor specimens. Additionally, 183 patients with multiple
      sclerosis (MS) undergoing therapy with IFN-beta were tested in the reporter gene
      assay. Percent positivity for NAbs to the IFN-beta was as follows: Avonex
      (1alpha) 26.5%, Rebif (1alpha) 34.1%, and Betaseron (1beta) 31.8%. The IFN-beta
      reporter gene assay showed excellent correlation with the well-established CPE
      assay offering clear advantages. The 50% false-positivity rate typically seen in
      enzyme-linked immunosorbent assays could be eliminated by using a functional
      assay for both screening and titering. Results can be reported within 20 h, and
      the cell line is cryopreserved, eliminating the need to maintain live viral and
      cell cultures. The use of this functional assay should be a valuable tool for
      detecting and monitoring the presence of NAbs in IFN-beta-treated patients with
      MS.

PMID- 23153302
TI  - Silicate mineral impacts on the uptake and storage of arsenic and plant nutrients
      in rice ( Oryza sativa L.).
AB  - Arsenic-contaminated rice grain may threaten human health globally. Since H3AsO30
      is the predominant As species found in paddy pore-waters, and H4SiO40 and H3AsO30
      share an uptake pathway, silica amendments have been proposed to decrease As
      uptake and consequent As concentrations in grains. Here, we evaluated the impact
      of two silicate mineral additions differing in solubility (+Si(L), diatomaceous
      earth, 0.29 mM Si; +Si(H), Si-gel, 1.1 mM Si) to soils differing in mineralogy on
      arsenic concentration in rice. The +Si(L) addition either did not change or
      decreased As concentration in pore-water but did not change or increased grain-As
      levels relative to the (+As--Si) control. The +Si(H) addition increased As in
      pore-water, but it significantly decreased grain-As relative to the (+As--Si)
      control. Only the +Si(H) addition resulted in significant increases in straw- and
      husk-Si. Total grain- and straw-As was negatively correlated with pore-water Si,
      and the relationship differed between two soils exhibiting different mineralogy.
      These differing results are a consequence of competition between H4SiO40 and
      H3AsO30 for adsorption sites on soil solids and subsequent plant-uptake, and
      illustrate the importance of Si mineralogy on arsenic uptake.

PMID- 23153301
TI  - Investigating the dearomative rearrangement of biaryl phosphine-ligated Pd(II)
      complexes.
AB  - A series of monoligated L.Pd(II)(Ar)X complexes (L = dialkyl biaryl phosphine)
      have been prepared and studied in an effort to better understand an unusual
      dearomative rearrangement previously documented in these systems. Experimental
      and theoretical evidence suggest a concerted process involving the unprecedented
      Pd(II)-mediated insertion of an aryl group into an unactivated arene.

PMID- 23153303
TI  - Metal and alloy nanoparticles by amine-borane reduction of metal salts by solid
      phase synthesis: atom economy and green process.
AB  - A new solid state synthetic route has been developed toward metal and bimetallic
      alloy nanoparticles from metal salts employing amine-boranes as the reducing
      agent. During the reduction, amine-borane plays a dual role: acts as a reducing
      agent and reduces the metal salts to their elemental form and simultaneously
      generates a stabilizing agent in situ which controls the growth of the particles
      and stabilizes them in the nanosize regime. Employing different amine-boranes
      with differing reducing ability (ammonia borane (AB), dimethylamine borane
      (DMAB), and triethylamine borane (TMAB)) was found to have a profound effect on
      the particle size and the size distribution. Usage of AB as the reducing agent
      provided the smallest possible size with best size distribution. Employment of
      TMAB also afforded similar results; however, when DMAB was used as the reducing
      agent it resulted in larger sized nanoparticles that are polydisperse too. In the
      AB mediated reduction, BNH(x) polymer generated in situ acts as a capping agent
      whereas, the complexing amine of the other amine-boranes (DMAB and TMAB) play the
      same role. Employing the solid state route described herein, monometallic Au, Ag,
      Cu, Pd, and Ir and bimetallic CuAg and CuAu alloy nanoparticles of <10 nm were
      successfully prepared. Nucleation and growth processes that control the size and
      the size distribution of the resulting nanoparticles have been elucidated in
      these systems.

PMID- 23153304
TI  - Antioxidant activity, total phenolic and total flavonoid contents of whole plant
      extracts Torilis leptophylla L.
AB  - BACKGROUND: The aim of this study was to screen various solvent extracts of whole
      plant of Torilis leptophylla to display potent antioxidant activity in vitro and
      in vivo, total phenolic and flavonoid contents in order to find possible sources
      for future novel antioxidants in food and pharmaceutical formulations. MATERIAL
      AND METHODS: A detailed study was performed on the antioxidant activity of the
      methanol extract of whole plant of Torilis leptophylla (TLM) and its derived
      fractions {n-hexane (TLH), chloroform (TLC) ethyl acetate (TLE) n-butanol (TLB)
      and residual aqueous fraction (TLA)} by in vitro chemical analyses and carbon
      tetrachloride (CCl4) induced hepatic injuries (lipid peroxidation and glutathione
      contents) in male Sprague-Dawley rat. The total yield, total phenolic (TPC) and
      total flavonoid contents (TFC) of all the fractions were also determined. TLM was
      also subjected to preliminary phytochemical screening test for various
      constituents. RESULTS: The total phenolic contents (TPC) (121.9+/-3.1 mg GAE/g
      extract) of TLM while total flavonoid contents (TFC) of TLE (60.9 +/-2.2 mg RTE/g
      extract) were found significantly higher as compared to other solvent fractions.
      Phytochemical screening of TLM revealed the presence of alkaloids,
      anthraquinones, cardiac glycosides, coumarins, flavonoids, saponins,
      phlobatannins, tannins and terpenoids. The EC50 values based on the DPPH (41.0+/
      1 MUg/ml), ABTS (10.0+/-0.9 MUg/ml) and phosphomolybdate (10.7+/-2 MUg/ml) for
      TLB, hydroxyl radicals (8.0+/-1 MUg/ml) for TLC, superoxide radicals (57.0+/-0.3
      MUg/ml) for TLM and hydrogen peroxide radicals (68.0+/-2 MUg/ml) for TLE were
      generally lower showing potential antioxidant properties. A significant but
      marginal positive correlation was found between TPC and EC50 values for DPPH,
      hydroxyl, phosphomolybdate and ABTS, whereas another weak and positive
      correlation was determined between TFC and EC50 values for superoxide anion and
      hydroxyl radicals. Results of in vivo experiment revealed that administration of
      CCl4 caused a significant increase in lipid peroxidation (TBARS) while decrease
      in GSH contents of liver. In contrast, TLM (200 mg/kg bw) and silymarin (50 mg/kg
      bw) co-treatment effectively prevented these alterations and maintained the
      antioxidant status. CONCLUSION: Data from present results revealed that Torilis
      leptophylla act as an antioxidant agent due to its free radical scavenging and
      cytoprotective activity.

PMID- 23153305
TI  - Separating stimulus-driven and response-related LRP components with Residue
      Iteration Decomposition (RIDE).
AB  - When the lateralized readiness potential (LRP) is recorded in stimulus-response
      compatibility (SRC) tasks, two processes may overlap in the LRP, stimulus-driven
      response priming and activation based on response selection rules. These
      overlapping processes are hard to disentangle with standard analytical tools.
      Here, we show that Residue Iteration Decomposition (RIDE), based on latency
      variability, separates the overlapping LRP components from a Simon task into
      stimulus-driven and response-related components. SRC affected LRP amplitudes only
      in the stimulus-driven component, whereas LRP onsets were affected only in the
      response-locked component. Importantly, the compatibility effect in reaction
      times was more similar to the effect in the onsets of the RIDE-derived response
      locked LRP component than in the unseparated LRP. Thus, RIDE-separated LRP
      components are devoid of distortions inherent to standard LRPs.

PMID- 23153306
TI  - Molecular evidence for the occurrence of Japanese encephalitis virus genotype I
      and III infection associated with acute encephalitis in patients of West Bengal,
      India, 2010.
AB  - BACKGROUND: Japanese encephalitis virus (JEV), a mosquito-borne zoonotic
      pathogen, is the sole etiologic agent of Japanese Encephalitis (JE); a
      neurotropic killer disease which is one of the major causes of viral encephalitis
      worldwide with prime public health concern. JE was first reported in the state of
      West Bengal, India in 1973. Since then it is being reported every year from
      different districts of the state, though the vaccination has already been done.
      Therefore, it indicates that there might be either partial coverage of the
      vaccine or the emergence of mutated/new strain of JEV. Considering this fact, to
      understand the JEV genotype distribution, we conducted a molecular
      epidemiological study on a total of 135 serum/cerebrospinal fluid (CSF) samples
      referred and/or collected from the clinically suspected patients with Acute
      encephalitis syndrome (AES), admitted in different district hospitals of West
      Bengal, India, 2010. FINDINGS: JEV etiology was confirmed in 36/135 (26.6%) and
      13/61 (21.3%) 2-15 days' febrile illness samples from AES cases by analyzing Mac
      ELISA followed by RT-PCR test respectively. Phylogenetic analysis based on
      complete envelope gene sequences of 13 isolates showed the emergence of JEV
      genotype I (GI), co-circulating with genotype III (GIII). CONCLUSION: This study
      represents the first report of JEV GI with GIII, co-circulating in West Bengal.
      The efficacy of the vaccine (derived from JEV GIII strain SA-14-14-2) to protect
      against emerging JEV GI needs careful evaluation. In future, JE outbreak is quite
      likely in the state, if this vaccine fails to protect sufficiently against GI of
      JEV.

PMID- 23153307
TI  - Structure dependence of long-chain [18F]fluorothia fatty acids as myocardial
      fatty acid oxidation probes.
AB  - In vivo imaging of regional fatty acid oxidation (FAO) rates would have
      considerable potential for evaluation of mammalian diseases. We have synthesized
      and evaluated 18F-labeled thia fatty acid analogues as metabolically trapped FAO
      probes to understand the effect of chain length, degree of unsaturation, and
      placement of the thia substituent on myocardial uptake and retention. 18
      [18F]Fluoro-4-thia-(9Z)-octadec-9-enoic acid (3) showed excellent
      heart/background radioactivity concentration ratios along with highest retention
      in heart and liver. Pretreatment of rats with the CPT-1 inhibitor, POCA, caused
      >80% reduction in myocardial uptake of 16-[18F]fluoro-4-thiahexadecanoic acid (2)
      and 3, indicating high specificity for FAO. In contrast, 18-[18F]fluoro-4
      thiaoctadecanoic acid (4) showed dramatically reduced myocardial uptake and
      blunted response to POCA. 18-[18F]Fluoro-6-thiaoctadecanoic acid (5) showed
      moderate myocardial uptake and no sensitivity of myocardial uptake to POCA. The
      results demonstrate relationships between structures of 18F-labeled thia fatty
      acid and uptake and their utility as FAO probes in various tissues.

PMID- 23153309
TI  - A weight of evidence approach for hazard screening of engineered nanomaterials.
AB  - Hazard identification is an important step in assessing nanomaterial risk and is
      required under multiple regulatory frameworks in the US, Europe and worldwide.
      Given the emerging nature of the field and complexity of nanomaterials, multiple
      studies on even basic material properties often result in varying data pointing
      in different directions when data interpretation is attempted. Weight of evidence
      (WOE) evaluation has been recommended for nanomaterial risk assessment, but the
      majority of WOE frameworks are qualitative in nature and do not satisfy the
      growing needs for objectivity and transparency that are necessary for regulatory
      decision making. This paper implements a quantitative WOE framework that utilizes
      multi-criteria decision analysis methodology for integrating individual studies
      on nanomaterial hazard resulting from physico-chemical and toxicological
      properties of nanomaterials. For the first time, a WOE approach explicitly
      integrates expert evaluation of data quality of available information.
      Application of the framework is illustrated for titanium dioxide nanoparticles
      (nano-TiO2), but the approach is designed to compare the relative hazard of
      several nanomaterials as well as emerging stressors in general.

PMID- 23153308
TI  - First survey and functional annotation of prohormone and convertase genes in the
      pig.
AB  - BACKGROUND: The pig is a biomedical model to study human and livestock traits.
      Many of these traits are controlled by neuropeptides that result from the
      cleavage of prohormones by prohormone convertases. Only 45 prohormones have been
      confirmed in the pig. Sequence homology can be ineffective to annotate prohormone
      genes in sequenced species like the pig due to the multifactorial nature of the
      prohormone processing. The goal of this study is to undertake the first complete
      survey of prohormone and prohormone convertases genes in the pig genome. These
      genes were functionally annotated based on 35 gene expression microarray
      experiments. The cleavage sites of prohormone sequences into potentially active
      neuropeptides were predicted. RESULTS: We identified 95 unique prohormone genes,
      2 alternative calcitonin-related sequences, 8 prohormone convertases and 1
      cleavage facilitator in the pig genome 10.2 assembly and trace archives. Of
      these, 11 pig prohormone genes have not been reported in the UniProt, UniGene or
      Gene databases. These genes are intermedin, cortistatin, insulin-like 5,
      orexigenic neuropeptide QRFP, prokineticin 2, prolactin-releasing peptide,
      parathyroid hormone 2, urocortin, urocortin 2, urocortin 3, and urotensin 2
      related peptide. In addition, a novel neuropeptide S was identified in the pig
      genome correcting the previously reported pig sequence that is identical to the
      rabbit sequence. Most differentially expressed prohormone genes were under
      expressed in pigs experiencing immune challenge relative to the un-challenged
      controls, in non-pregnant relative to pregnant sows, in old relative to young
      embryos, and in non-neural relative to neural tissues. The cleavage prediction
      based on human sequences had the best performance with a correct classification
      rate of cleaved and non-cleaved sites of 92% suggesting that the processing of
      prohormones in pigs is similar to humans. The cleavage prediction models did not
      find conclusive evidence supporting the production of the bioactive neuropeptides
      urocortin 2, urocortin 3, torsin family 2 member A, tachykinin 4, islet amyloid
      polypeptide, and calcitonin receptor-stimulating peptide 2 in the pig.
      CONCLUSIONS: The present genomic and functional characterization supports the use
      of the pig as an effective animal model to gain a deeper understanding of
      prohormones, prohormone convertases and neuropeptides in biomedical and
      agricultural research.

PMID- 23153310
TI  - Immunohistochemical analysis based Ep-ICD subcellular localization index (ESLI)
      is a novel marker for metastatic papillary thyroid microcarcinoma.
AB  - BACKGROUND: Thyroid cancer is among the fastest growing malignancies; almost
      fifty-percent of these rapidly increasing incidence tumors are less than or equal
      to 1cm in size, termed papillary thyroid microcarcinoma (PTMC). The management of
      PTMC remains a controversy due to differing natural history of these patients.
      Epithelial cell adhesion molecule (EpCAM) is comprised of an extracellular domain
      (EpEx), a single transmembrane domain and an intracellular domain (Ep-ICD). Our
      group reported nuclear Ep-ICD correlated with poor prognosis in thyroid cancer
      (Ralhan et al., BMC Cancer 2010,10:331). Here in, we hypothesized nuclear and
      cytoplasmic accumulation of Ep-ICD and loss of membranous EpEx may aid in
      distinguishing metastatic from non-metastatic PTMC, which is an important current
      clinical challenge. To test our hypothesis, Ep-ICD and EpEx expression levels
      were analyzed in PTMC and the staining was correlated with metastatic potential
      of these carcinomas. METHODS: Thirty-six PTMC patients (tumor size 0.5 - 1cm;
      metastatic 8 cases and non-metastatic 28 cases) who underwent total thyroidectomy
      were selected. The metastatic group consisted of patients who developed lymph
      node or distant metastasis at diagnosis or during follow up. The patients'
      tissues were stained for Ep-ICD and EpEx using domain specific antibodies by
      immunohistochemistry and evaluated. RESULTS: PTMC patients with metastasis had
      higher scores for nuclear and cytoplasmic Ep-ICD immunostaining than the patients
      without metastasis (1.96 +/- 0.86 vs. 1.22 +/- 0.45; p = 0.007 and 5.37 +/- 0.33
      vs. 4.72 +/- 1.07; p = 0.016, respectively). Concomitantly, the former had lower
      scores for membrane EpEx than the non-metastatic group (4.64 +/- 1.08 vs. 5.64 +/
      1.51; p = 0.026). An index of aggressiveness, Ep-ICD subcellular localization
      index (ESLI), was defined as sum of the IHC scores for accumulation of nuclear
      and cytoplasmic Ep-ICD and loss of membranous EpEx; ESLI = [Ep - ICDnuc + Ep -
      ICDcyt + loss of membranous EpEx]. Notably, ESLI correlated significantly with
      lymph node metastasis in PTMC (p = 0.008). CONCLUSION: Nuclear and cytoplasmic Ep
      ICD expression and loss of membranous EpEx were found to correlate positively
      with metastasis in PTMC patients. In addition, ESLI had the potential to identify
      metastatic behavior in PTMC which could serve as a valuable tool for solving a
      current dilemma in clinical practice.

PMID- 23153311
TI  - Monitoring the impact of decentralised chronic care services on patient travel
      time in rural Africa--methods and results in Northern Malawi.
AB  - BACKGROUND: Decentralised health services form a key part of chronic care
      strategies in resource-limited settings by reducing the distance between patient
      and clinic and thereby the time and costs involved in travelling. However, few
      tools exist to evaluate the impact of decentralisation on patient travel time or
      what proportion of patients attend their nearest clinic. Here we develop methods
      to monitor changes in travel time, using data from the antiretroviral therapy
      (ART) roll-out in a rural district in North Malawi. METHODS: Clinic position was
      combined with GPS information on the home village of patients accessing ART
      services in Karonga District (North Malawi) between July 2005 and July 2009.
      Potential travel time was estimated as the travel time for an individual
      attending their nearest clinic, and estimated actual travel time as the time to
      the clinic attended. This allowed us to calculate changes in potential and actual
      travel time as new clinics opened and track the proportion and origin of patients
      not accessing their nearest clinic. RESULTS: The model showed how the opening of
      further ART clinics in Karonga District reduced median potential travel time from
      83 to 43 minutes, and median actual travel time fell from 83 to 47 minutes. The
      proportion of patients not attending their nearest clinic increased from 6% when
      two clinics were open, to 12% with four open. DISCUSSION: Integrating GPS
      information with patient data shows the impact of decentralisation on travel time
      and clinic choice to inform policy and research questions. In our case study,
      travel time decreased, accompanied by an increased uptake of services. However,
      the model also identified an increasing proportion of ART patients did not attend
      their nearest clinic.

PMID- 23153312
TI  - Clinical efficacy and safety evaluation of a monopolar radiofrequency device with
      a new vibration handpiece for the treatment of facial skin laxity: a 10-month
      experience with 64 patients.
AB  - BACKGROUND: Although ablative laser technology and surgical treatment are
      considered to be the criterion standard for the rejuvenation of aging skin, the
      demand for procedures with less down time and risk, such as nonablative laser and
      radiofrequency (RF) treatments, has increased over the last several decades.
      OBJECTIVES: To investigate the efficacy and safety of the newest generation of
      monopolar RF (mRF) devices by evaluating our patients after treatment. METHODS
      AND MATERIALS: Sixty-four patients with mild to moderate facial skin laxity were
      treated using the new mRF with vibration handpiece. Patients were surveyed
      between 1-10 months after treatment to determine degree of improvement,
      satisfaction, and presence of side effects. RESULTS: With the new system, 80% (n
      = 51) reported at least mild correction of skin laxity, 55% (n = 35) noticed skin
      texture improvement, average pain level was 6.06 (0-10 scale), 9% (n = 6) found
      the procedure too painful, and 43% (n = 28) would have the procedure again.
      CONCLUSION: The new mRF system was safely tolerated and efficacious for most
      patients for facial treatment sites.

PMID- 23153313
TI  - Prevalence of beta-thalassemia trait and abnormal hemoglobin in premarital
      screening in the province of Izmir, Turkey.
AB  - BACKGROUND/AIMS: Thalassemia is one of the most common hereditary disorders in
      Turkey. The aim of our study was to determine the prevalence of the beta
      thalassemia trait and abnormal hemoglobin in couples who applied for premarital
      screening in the third largest Turkish province of Izmir in the Aegean region.
      METHODS: From January 2011 to March 2012, we tested 19,277 couples at the
      Karsiyaka Public Health Laboratory, Thalassemia Unit for the beta-thalassemia
      trait and abnormal hemoglobin using a high-performance liquid chromatograph, a
      hematology analyzer. RESULTS: The beta-thalassemia trait with increased HbA2
      (>3.5%) and abnormal hemoglobin was found in 4.96% (1912/38,554) and 0.53%
      (206/38,554) people, respectively. Of abnormal hemoglobin findings, HbS was
      determined in 128 people (0.33%), HbD in 50 (0.13%), HbE in 24 (0.06%), and HbC
      in four (0.01%). Furthermore, in 20 of the 19,277 couples (0.05%), both partners
      had the beta-thalassemia trait and were referred to counseling. CONCLUSION: The
      prevalence of the beta-thalassemia trait in the province of Izmir is high
      compared with other cities of Turkey. Izmir is a high-risk province for beta
      thalassemia and sickle-cell anemia. Therefore, premarital screening is essential
      to prevent new hereditary hemoglobinopaties.

PMID- 23153314
TI  - Soil-based treatments of mechanically collected cyanobacterial blooms from Lake
      Taihu: efficiencies and potential risks.
AB  - In China, mechanical collection of cyanoblooms followed by soil-based treatments
      has been widely used as emergency strategies in many eutrophicated freshwaters.
      This study was to evaluate both efficiencies and potential risks of typical soil
      based technologies. Results from this study indicated that over 90% of
      cyanobacterial biomass and 96% of dissolved microcystins (MCs) could be
      restrained in soils via three-level systems, which were much better than single
      level systems. High concentrations of MCs, ranged from 65 to 276 ng g-1 and from
      2.12 to 6.6 ng g-1, were found in soils around treatment systems and croplands,
      respectively. In the soil solutions, MCs ranged from 0.35 to 2.0 MUg L-1, showing
      a potentially high leaching risk. In the samples from shallow groundwater near
      the treatment systems, MC concentrations were detected as high as 1.2 MUg L-1.
      Moreover, bioaccumulations of MCs varied between 22 and 365 MUg kg-1, and 19-222
      MUg kg-1 were found in 13 kinds of crops and 7 kinds of wild grass, respectively.
      Our results indicated for the first time that current soil-based technologies
      were effective but could pose potential environmental, ecological, and public
      health risks. Further improvements of these technologies were also proposed based
      on our findings.

PMID- 23153315
TI  - Detailed transient heme structures of Mb-CO in solution after CO dissociation: an
      X-ray transient absorption spectroscopic study.
AB  - Although understanding the structural dynamics associated with ligand
      photodissociation is necessary in order to correlate structure and function in
      biological systems, few techniques are capable of measuring the ultrafast
      dynamics of these systems in solution-phase at room temperature. We present here
      a detailed X-ray transient absorption (XTA) study of the photodissociation of CO
      bound myoglobin (Fe(II)CO-Mb) in room-temperature aqueous buffer solution with a
      time resolution of 80 ps, along with a general procedure for handling biological
      samples under the harsh experimental conditions that transient X-ray experiments
      entail. The XTA spectra of (Fe(II)CO-Mb) exhibit significant XANES and XAFS
      alterations following 527 nm excitation, which remain unchanged for >47 MUs.
      These spectral changes indicate loss of the CO ligand, resulting in a five
      coordinate, domed heme, and significant energetic reorganization of the 3d
      orbitals of the Fe center. With the current experimental setup, each X-ray pulse
      in the pulse train, separated by ~153 ns, can be separately discriminated,
      yielding snapshots of the myoglobin evolution over time. These methods can be
      easily applied to other biological systems, allowing for simultaneous structural
      and electronic measurements of any biological system with both ultrafast and slow
      time resolutions, effectively mapping out all of the samples' relevant
      physiological processes.

PMID- 23153316
TI  - Reactions of the cumyloxyl and benzyloxyl radicals with strong hydrogen bond
      acceptors. Large enhancements in hydrogen abstraction reactivity determined by
      substrate/radical hydrogen bonding.
AB  - A kinetic study on hydrogen abstraction from strong hydrogen bond acceptors such
      as DMSO, HMPA, and tributylphosphine oxide (TBPO) by the cumyloxyl (CumO(*)) and
      benzyloxyl (BnO(*)) radicals was carried out in acetonitrile. The reactions with
      CumO(*) were described in terms of a direct hydrogen abstraction mechanism, in
      line with the kinetic deuterium isotope effects, k(H)/k(D), of 2.0 and 3.1
      measured for reaction of this radical with DMSO/DMSO-d(6) and HMPA/HMPA-d(18).
      Very large increases in reactivity were observed on going from CumO(*) to BnO(*),
      as evidenced by k(H)(BnO(*))/k(H)(CumO(*)) ratios of 86, 4.8 * 10(3), and 1.6 *
      10(4) for the reactions with HMPA, TBPO, and DMSO, respectively. The k(H)/k(D) of
      0.91 and 1.0 measured for the reactions of BnO(*) with DMSO/DMSO-d(6) and
      HMPA/HMPA-d(18), together with the k(H)(BnO(*))/k(H)(CumO(*)) ratios, were
      explained on the basis of the formation of a hydrogen-bonded prereaction complex
      between the benzyloxyl alpha-C-H and the oxygen atom of the substrates followed
      by hydrogen abstraction. This is supported by theoretical calculations that show
      the formation of relatively strong prereaction complexes. These observations
      confirm that in alkoxyl radical reactions specific hydrogen bond interactions can
      dramatically influence the hydrogen abstraction reactivity, pointing toward the
      important role played by structural and electronic effects.

PMID- 23153317
TI  - Prognostic value of admission heart rate in patients with ST-segment elevation
      myocardial infarction: role of type 2 diabetes mellitus.
AB  - BACKGROUND: It's unknown whether the prognostic value of admission heart rate
      (HR) was different in patients with ST-segment elevation myocardial infarction
      (STEMI) with or without concomitant type 2 diabetes mellitus (T2DM). METHODS:
      Consecutive STEMI patients who presented within 12 hours of symptom onset were
      recruited from 274 hospitals in China. Participants were stratified into
      quartiles by admission HR. Baseline characteristics, current therapeutic
      recommenda- tions, laboratory biochemical tests, 30-day all-cause mortality and
      Cardiovascular Events (CVE, including all-cause death, reinfarction and stroke)
      were compared across admission HR quartiles. RESULTS: We evaluated 7294 STEMI
      patients, of these 820 (11.2%) had known T2DM. The admission HR quartile
      stratification was significantly associated with all-cause mortality and CVE
      regardless of T2DM status (P < 0.001 both for survival and CVE). After adjusted
      other risk factors, in patients without T2DM, comparing with HR <66 b.p.m., the
      increase of HR level was associated with worse prognosis (P < 0.05). In patients
      with T2DM, the hazard ratios for 30-day CVE were 1.75 (95%CI), 1.92 (95%CI), 3.00
      (95%CI) in the HR of 66-76 b.p.m., 77-88 b.p.m., and >88 b.p.m., respectively.
      Results were similar for 30-day all-cause mortality, but the hazard ratios in Q2
      (P = 0.139 and P =0.086 for survival and CVE, respectively) and Q3 groups were
      non-significant (P = 0.072 and P =0.033 for survival and CVE, respectively).
      There was a significant interaction effect of HR and T2DM on 30-day CVE mortality
      (P = 0.035), which was not found on all-cause mortality (P = 0.126). CONCLUSION:
      Admission heart rate was an important risk factor of 30-day all-cause mortality
      and CVE in patients with STEMI with or without T2DM. However, the predictive
      effect was modified by T2DM.

PMID- 23153318
TI  - Budget impact analysis of everolimus for the treatment of hormone receptor
      positive, human epidermal growth factor receptor-2 negative (HER2-) advanced
      breast cancer in the United States.
AB  - OBJECTIVE: To estimate the budget impact of everolimus as the first and second
      treatment option after letrozole or anastrozole (L/A) failure for post-menopausal
      women with hormone receptor positive (HR+), human epidermal growth factor
      receptor-2 negative (HER2-) advanced breast cancer (ABC). METHODS: Pharmacy and
      medical budget impacts (2011 USD) were estimated over the first year of
      everolimus use in HR+, HER2- ABC from a US payer perspective. Epidemiology data
      were used to estimate target population size. Pre-everolimus entry treatment
      options included exemestane, fulvestrant, and tamoxifen. Pre- and post-everolimus
      entry market shares were estimated based on market research and assumptions. Drug
      costs were based on wholesale acquisition cost. Patients were assumed to be on
      treatment until progression or death. Annual medical costs were calculated as the
      average of pre- and post-progression medical costs weighted by the time in each
      period, adjusted for survival. One-way and two-way sensitivity analyses were
      conducted to assess the model robustness. RESULTS: In a hypothetical 1,000,000
      member plan, 72 and 159 patients were expected to be candidates for everolimus
      treatment as first and second treatment option, respectively, after L/A failure.
      The total budget impact for the first year post-everolimus entry was $0.044 per
      member per month [PMPM] (pharmacy budget: $0.058 PMPM; medical budget: -$0.014
      PMPM), assuming 10% of the target population would receive everolimus. The total
      budget impacts for the first and second treatment options after L/A failure were
      $0.014 PMPM (pharmacy budget: $0.018; medical budget: -$0.004) and $0.030 PMPM
      (pharmacy budget: $0.040; medical budget: -$0.010), respectively. Results
      remained robust in sensitivity analyses. LIMITATIONS: Assumptions about some
      model input parameters were necessary and may impact results. CONCLUSIONS:
      Increased pharmacy costs for HR+, HER2- ABC following everolimus entry are
      expected to be partially offset by reduced medical service costs. Pharmacy and
      total budget increases were modest.

PMID- 23153319
TI  - Economic burden of dermatologic adverse drug reactions in the treatment of
      colorectal, non-small cell lung, and head and neck cancers with epidermal growth
      factor receptor inhibitors.
AB  - BACKGROUND: Patients treated with epidermal growth factor receptor inhibitors
      (EGFRIs) may develop dermatologic adverse drug reactions (ADRs) that may affect
      patients' quality-of-life, require medical care, and may lead to substantial
      costs. This study assessed the economic burden of dermatologic ADRs in colorectal
      cancer (CRC), head and neck cancer (HNC), and non-small cell lung cancer (NSCLC)
      patients. METHODS: Adult patients with >=1 diagnosis for the study cancer
      initiated on EGFRIs indicated for CRC, HNC, and NSCLC were selected from a large
      commercial database (MarketScan Commercial Database [2000-2010]; Thomas Reuters,
      New York, NY). For each cancer type, patients were classified into two mutually
      exclusive cohorts: 'ADR' (patients with >=1 ADR following EGFRI initiation) and
      'ADR-free' (patients without any ADR). Patients were observed from the index date
      up to the end of continuous healthcare plan enrollment or 90 days after EGFRI
      discontinuation, whichever occurred first. For each cancer group, the proportion
      of patients and the incidence rate (IR) of experiencing >=1 dermatologic ADR were
      reported. Incidence rate ratios for healthcare resource utilization and monthly
      incremental costs (2010 USD) were estimated using Poisson regression and
      generalized linear or two-part models, respectively. RESULTS: Overall, the
      proportion of patients with >=1 ADR ranged between 20.5-36.4% across cancer
      groups (IR ranged between 44.2-57.4 per 100 patient-years). After adjusting for
      confounders, in each cancer group, ADR patients had higher incidence of
      healthcare resource utilization, generally driven by higher incidence of
      emergency room visits and incurred incremental total monthly healthcare costs
      that ranged between $2284-$3210 across cancer groups. LIMITATIONS: There was no
      clinical measure of cancer staging and ADR severity in the database. CONCLUSIONS:
      Results suggest that patients with CRC, NSCLC, and HNC, who may benefit from
      EGFRI therapies, may also incur a substantial economic burden that is associated
      with dermatologic ADRs.

PMID- 23153320
TI  - 'A chronic disease is a disease which keeps coming back...it is like the flu':
      chronic disease risk perception and explanatory models among French- and Swahili
      speaking African migrants.
AB  - BACKGROUND: African migrants to the West are at increased risk of hypertensive
      related diseases and certain cancers compared with other ethnic groups. Little is
      known about their awareness of this risk or knowledge of associated risk factors.
      OBJECTIVES: To explore African migrants' perceptions of chronic disease risk,
      risk factors and underlying explanatory models. DESIGN: In-depth interviews with
      19 Africans from French- or Swahili-speaking countries living in Glasgow were
      conducted. Interviews were transcribed and 10 translated (3 Swahili and 7
      French). Analysis was informed by a grounded theory approach. RESULTS: Narratives
      suggested low awareness of chronic disease risk among participants. Africans
      reported a positive outlook on life that discouraged thought about future
      sickness. Infectious diseases were considered the dominant health threat for
      African migrants, mainly HIV but also TB and 'flu'. Chronic diseases were
      sometimes described as contagious. Explanatory models of chronic disease included
      bodily/dietary imbalance, stress/exertion, heredity/predisposition and food
      contamination. Cancer was feared but not considered a major threat. Cancer was
      considered more common in Europe than Africa and attributed to chemical
      contamination from fertilisers, food preservatives and industrial pollution.
      Evidence cited for these chemicals was rapid livestock/vegetable production,
      large size of livestock (e.g., fish), softness of meat and flavourless food.
      Chemicals were reported to circulate silently inside the body and cancer to form
      in the part where they deposit, sometimes years later. Cardiovascular diseases
      were described in terms of acute symptoms that required short-term medication.
      Confidentiality concerns were reported to prevent discussion of chronic disease
      between Africans. CONCLUSION: This study suggests a need to improve chronic
      disease health literacy among African migrants to promote engagement with
      preventive behaviours. This should build on not only participants' existing
      knowledge of disease causation and risk factors but also their self-reliance in
      the pursuit of a healthy lifestyle and desire to retain cultural knowledge and
      practice.

PMID- 23153321
TI  - Dynamics of regional lung aeration determined by electrical impedance tomography
      in patients with acute respiratory distress syndrome.
AB  - BACKGROUND: Lung tissue of patients with acute respiratory distress syndrome
      (ARDS) is heterogeneously damaged and prone to develop atelectasis. During
      inflation, atelectatic regions may exhibit alveolar recruitment accompanied by
      prolonged filling with air in contrast to regions with already open alveoli with
      a fast increase in regional aeration. During deflation, derecruitment of injured
      regions is possible with ongoing loss in regional aeration. The aim of our study
      was to assess the dynamics of regional lung aeration in mechanically ventilated
      patients with ARDS and its dependency on positive end-expiratory pressure (PEEP)
      using electrical impedance tomography (EIT). METHODS: Twelve lung healthy and
      twenty ARDS patients were examined by EIT during sustained step increases in
      airway pressure from 0, 8 and 15 cm H2O to 35 cm H2O and during subsequent step
      decrease to the corresponding PEEP. Regional EIT waveforms in the ventral and
      dorsal lung regions were fitted to bi-exponential equations. Regional fast and
      slow respiratory time constants and the sizes of the fast and slow compartments
      were subsequently calculated. RESULTS: ARDS patients exhibited significantly
      lower fast and slow time constants than the lung healthy patients in ventral and
      dorsal regions. The time constants were significantly affected by PEEP and
      differed between the regions. The size of the fast compartment was significantly
      lower in ARDS patients than in patients with healthy lung under all studied
      conditions. CONCLUSION: These results show that regional lung mechanics can be
      assessed by EIT. They reflect the lower respiratory system compliance of injured
      lungs and imply more pronounced regional recruitment and derecruitment in ARDS
      patients.

PMID- 23153322
TI  - Salivary gland function 5 years after radioactive iodine ablation in patients
      with differentiated thyroid cancer: direct comparison of pre- and postablation
      scintigraphies and their relation to xerostomia symptoms.
AB  - BACKGROUND: Chronic sialadenitis is one of the most frequent chronic
      complications after radioactive iodine (RAI) therapy for thyroid cancer. To
      evaluate the long-term effects of RAI ablation on salivary gland function, we
      investigated scintigraphic changes in salivary glands by direct comparison of two
      salivary gland scintigraphies (SGSs) taken before and at 5 years after an RAI
      ablation. METHODS: SGS was performed just before RAI ablation (pre-SGS) and ~5
      years after RAI ablation (F/U SGS) in 213 subjects who underwent thyroidectomy
      for thyroid cancer. The uptake score (U score) was graded, and the ejection
      fraction (EF) was quantified for the parotid and submandibular glands at pre-SGS
      and F/U SGS. Changes in salivary gland function were graded as mild, moderate, or
      severe according to the differences in U score and EF between the two SGSs.
      Xerostomia was assessed and compared with the SGS findings. RESULTS: Worsening of
      the U score was observed in 182 of 852 salivary glands (total: 21.3%; mild: 4.2%,
      moderate: 7.4%, severe: 9.7%), and 47.4% of the patients had a worsening U score
      for at least one of four salivary glands. A decrease in EF was observed in 173 of
      852 salivary glands (total: 20.3%; mild: 5.4%, moderate: 6.8%, severe: 8.1%), and
      43.7% of the patients experienced a decrease in the EF of at least one of the
      four salivary glands. Bilateral parotid gland dysfunction was the most commonly
      observed condition. Thirty-five (16.4%) patients complained of xerostomia at 5
      years after RAI ablation. Scintigraphic changes in salivary gland function and
      xerostomia were more common in patients receiving 5.55 GBq, compared with 3.7
      GBq. Xerostomia was more common in patients with submandibular gland dysfunction
      than those with parotid gland dysfunction (68.8% vs. 33.3%, p<0.05). The number
      of dysfunctional salivary glands was correlated with xerostomia (p<0.01).
      CONCLUSION: About 20% of the salivary glands were dysfunctional on SGS 5 years
      after a single RAI ablation, especially in patients who received higher doses of
      RAI. While parotid glands are more susceptible to (131)I-related damage,
      xerostomia was more associated with submandibular gland dysfunction and the
      prevalence of dysfunctional salivary glands.

PMID- 23153323
TI  - An electrophysiological analysis of contextual and temporal constraints on
      parafoveal word processing.
AB  - During natural reading, parafoveal information is processed to some degree.
      Although isolated words can be fully processed in the parafovea, not all sentence
      reading experiments have found evidence of semantic processing in the parafovea.
      We suggest a possible reconciliation for these mixed results via two ERP studies
      in which volunteers read sentences presented word by word at fixation, flanked
      bilaterally by the next word to its right and the previous word to its left. Half
      the words in the right parafovea of critical triads and in the fovea for the
      subsequent triad were semantically incongruent. The conditions under which
      parafoveal words elicit canonical visual N400 congruity effects suggest that they
      are processed in parallel with foveal words, but that the extraction of semantic
      information parafoveally is a function of contextual constraint and presentation
      rate, most likely under high contextual constraint and at slower rates.

PMID- 23153324
TI  - Characteristic molecular signature for early detection and prediction of
      persistent organic pollutants in rat liver.
AB  - Persistent organic pollutants (POPs) are degradation-resistant anthropogenic
      chemicals that accumulate in the food chain and in adipose tissue, and are among
      the most hazardous compounds ever synthesized. However, their toxic mechanisms
      are still undefined. To investigate whether characteristic molecular signatures
      can discriminate individual POP and provide prediction markers for the early
      detection of POPs exposure in an animal model, we performed transcriptomic
      analysis of rat liver tissues after exposure to POPs. The six different POPs
      (toxaphene, hexachlorobenzene, chlordane, mirex, dieldrin, and heptachlor) were
      administered to 11-week-old male Sprague-Dawley rats, and after 48 h of exposure,
      RNAs were extracted from liver tissues and subjected to rat whole genome
      expression microarrays. Early during exposure, conventional toxicological
      analysis including changes in the body and organ weight, histopathological
      examination, and blood biochemical analysis did not reflect any toxicant
      stresses. However, unsupervised gene expression analysis of rat liver tissues
      revealed in a characteristic molecular signature for each toxicant, and
      supervised analysis identified 2708 outlier genes that discerned the POPs
      exposure group from the vehicle-treated control. Combination analysis of two
      different multiclassifications suggested 384 genes as early detection markers for
      predicting each POP exposure with 100% accuracy. The data from large-scale gene
      expression analysis of a different POP exposure in rat model suggest that
      characteristic expression profiles exist in liver hepatic cells and
      multiclassification of POP-specific molecular signatures can discriminate each
      toxicant at an early exposure time. The use of these molecular markers may be
      more widely implemented in combination with more traditional techniques for
      assessment and prediction of toxicity exposure to POPs from an environmental
      aspect.

PMID- 23153325
TI  - Impact of sustained RNAi-mediated suppression of cellular cofactor Tat-SF1 on HIV
      1 replication in CD4+ T cells.
AB  - BACKGROUND: Conventional anti-HIV drug regimens targeting viral enzymes are
      plagued by the emergence of drug resistance. There is interest in targeting HIV
      dependency factors (HDFs), host proteins that the virus requires for replication,
      as drugs targeting their function may prove protective. Reporter cell lines
      provide a rapid and convenient method of identifying putative HDFs, but this
      approach may lead to misleading results and a failure to detect subtle
      detrimental effects on cells that result from HDF suppression. Thus, alternative
      methods for HDF validation are required. Cellular Tat-SF1 has long been ascribed
      a cofactor role in Tat-dependent transactivation of viral transcription
      elongation. Here we employ sustained RNAi-mediated suppression of Tat-SF1 to
      validate its requirement for HIV-1 replication in a CD4+ T cell-derived line and
      its potential as a therapeutic target. RESULTS: shRNA-mediated suppression of Tat
      SF1 reduced HIV-1 replication and infectious particle production from TZM-bl
      reporter cells. This effect was not a result of increased apoptosis, loss of cell
      viability or an immune response. To validate its requirement for HIV-1
      replication in a more relevant cell line, CD4+ SupT1 cell populations were
      generated that stably expressed shRNAs. HIV-1 replication was significantly
      reduced for two weeks (~65%) in cells with depleted Tat-SF1, although the
      inhibition of viral replication was moderate when compared to SupT1 cells
      expressing a shRNA targeting the integration cofactor LEDGF/p75. Tat-SF1
      suppression was attenuated over time, resulting from decreased shRNA guide strand
      expression, suggesting that there is a selective pressure to restore Tat-SF1
      levels. CONCLUSIONS: This study validates Tat-SF1 as an HDF in CD4+ T cell
      derived SupT1 cells. However, our findings also suggest that Tat-SF1 is not a
      critical cofactor required for virus replication and its suppression may affect
      cell growth. Therefore, this study demonstrates the importance of examining HIV-1
      replication kinetics and cytotoxicity in cells with sustained HDF suppression to
      validate their therapeutic potential as targets.

PMID- 23153326
TI  - Hydrogen peroxide induces overexpression of angiotensin-converting enzyme in
      human umbilical vein endothelial cells.
AB  - Oxidative stress has been linked to endothelial dysfunction in atherosclerosis
      and hypertension. The present study was designed to investigate the effect of
      hydrogen peroxide (H2O2) on angiotensin-converting enzyme (ACE), a key regulator
      of the renin-angiotensin system, and the mechanisms underlying ACE regulation in
      human umbilical vein endothelial cells (HUVECs). We used Tetrazolium bromide
      (MTT) assay for cell viability, terminal deoxynucleotidyl transferase-mediated
      dUTP nick end labeling (TUNEL) assay for cell apoptosis, enzyme-linked
      immunosorbent assay (ELISA) for cAMP measurement, real-time PCR for mRNA
      detection, and Western blot for protein analysis in the study. Our results
      demonstrated that H2O2 (50-1000 MUM) decreased HUVECs viability by inducing
      apoptosis. Notably, H2O2 upregulated ACE expression in a concentration-dependent
      manner. H2O2 100 MUM significantly enhanced cyclic adenosine monophosphate (cAMP)
      expression by 1.48-fold (P<0.05). Additionally, forskolin 10 MUM, a cAMP agonist,
      was also found to enhance ACE expression by 1.78-fold (P<0.05); in contrast, H-89
      10 MUM, a protein kinase A (PKA) inhibitor, abolished H2O2-induced ACE expression
      and prevented the enhancing effect of forskolin-induced ACE expression. Similar
      effects on ACE mRNA were also observed. cAMP-response element-specific decoy
      oligodeoxynucleotides (CRE-dODN) containing binding sites for cAMP-response
      element-binding protein (CREB) inhibited ACE expression at both the mRNA and
      protein levels. Negative control CRE-dODN had no effect on ACE expression. We
      conclude that H2O2 upregulates the expression of ACE through the activation of
      cAMP/PKA/CREB signal pathway in HUVECs, indicating a role of oxidative stress in
      the pathophysiology of hypertension.

PMID- 23153329
TI  - Contact de-electrification of electrostatically charged polymers.
AB  - The contact electrification of insulating organic polymers is still incompletely
      understood, in part because multiple fundamental mechanisms may contribute to the
      movement of charge. This study describes a mechanism previously unreported in the
      context of contact electrification: that is, "contact de-electrification", a
      process in which polymers charged to the same polarity discharge on contact. Both
      positively charged polymeric beads, e.g., polyamide 6/6 (Nylon) and
      polyoxymethylene (Delrin), and negatively charged polymeric beads, e.g.,
      polytetrafluoroethylene (Teflon) and polyamide-imide (Torlon), discharge when the
      like-charged beads are brought into contact. The beads (both with charges of ~+/
      20 MUC/m(2), or ~100 charges/MUm(2)) discharge on contact regardless of whether
      they are made of the same material, or of different materials. Discharge is
      rapid: discharge of flat slabs of like-charged Nylon and Teflon pieces is
      completed on a single contact (~3 s). The charge lost from the polymers during
      contact de-electrification transfers onto molecules of gas in the atmosphere.
      When like-charged polymers are brought into contact, the increase in electric
      field at the point of contact exceeds the dielectric breakdown strength of the
      atmosphere and ionizes molecules of the gas; this ionization thus leads to
      discharge of the polymers. The detection (using a Faraday cup) of charges
      transferred to the cup by the ionized gas is compatible with the mechanism.
      Contact de-electrification occurs for different polymers and in atmospheres with
      different values of dielectric breakdown strength (helium, argon, oxygen, carbon
      dioxide, nitrogen, and sulfur hexafluoride): the mechanism thus appears to be
      general.

PMID- 23153327
TI  - Behcet's Syndrome.
AB  - Behcet's syndrome (BS) is a vasculitis, seen more commonly around the
      Mediterranean and the Far East, and manifests with oral and genital ulcerations,
      skin lesions, uveitis, and vascular, central nervous system and gastrointestinal
      involvement. Its natural history of getting less severe over time, more severe
      disease in males and lack of specific diagnostic testing separates it from other
      commonly seen conditions in rheumatology. Most of the serious manifestations
      respond well to immunosuppression, and these are the mainstays of treatment for
      BS. BS is more prevalent in regions along the Silk Road, from the Mediterranean
      to the Far East. The genetic risk factor most strongly associated with BS is the
      human leukocyte antigen (HLA)-B51 allele. While genetic factors seem to play a
      role in the development of certain features of BS, there is general consensus
      that as yet unidentified environmental stimuli are necessary for initiation of
      disease. Proposed exogenous triggers include both bacterial and viral infections,
      which may then lead to dysregulation of the immune system, ultimately leading to
      the phenotypic expression of disease. The clinical manifestations of BS are
      protean in nature. While most patients develop mucocutaneous and genital ulcers
      along with eye disease, other patients may also present with arthritis, frank
      vasculitis, thrombophlebitis and CNS disease. Interestingly, the manifestations
      of this illness vary considerably based on gender and ethnicity. As the
      phenotypic expression among patients with BS is quite heterogeneous,
      pharmacological therapy is variable and dependent upon the severity of the
      disease as well as organ involvement. Treatment for BS overlaps considerably with
      therapies for other autoimmune diseases, including systemic lupus erythematosus,
      rheumatoid arthritis and the vasculitides. Pharmacological agents utilized for
      treatment of BS include corticosteroids, colchicine, azathioprine, and tumour
      necrosis factor (TNF).alpha inhibitors, among others. In this article, we review
      the salient clinical studies for each drug class along with important side
      effects as well as drug toxicity monitoring. Management of the patient with BS is
      complex and oftentimes requires a multidisciplinary approach. We discuss
      strategies to assess and stratify patients based on clinical manifestations and
      disease severity. A summary of drug toxicities as they relate to the
      aforementioned pharmacological agents, as well as guidelines regarding
      vaccinations in this patient population, are offered. Finally, we conclude with
      treatment strategies for the common manifestations of BS along with a discussion
      of the management of thrombotic disease in these patients.

PMID- 23153328
TI  - A genome wide association study for backfat thickness in Italian Large White pigs
      highlights new regions affecting fat deposition including neuronal genes.
AB  - BACKGROUND: Carcass fatness is an important trait in most pig breeding programs.
      Following market requests, breeding plans for fresh pork consumption are usually
      designed to reduce carcass fat content and increase lean meat deposition.
      However, the Italian pig industry is mainly devoted to the production of
      Protected Designation of Origin dry cured hams: pigs are slaughtered at around
      160 kg of live weight and the breeding goal aims at maintaining fat coverage,
      measured as backfat thickness to avoid excessive desiccation of the hams. This
      objective has shaped the genetic pool of Italian heavy pig breeds for a few
      decades. In this study we applied a selective genotyping approach within a
      population of ~ 12,000 performance tested Italian Large White pigs. Within this
      population, we selectively genotyped 304 pigs with extreme and divergent backfat
      thickness estimated breeding value by the Illumina PorcineSNP60 BeadChip and
      performed a genome wide association study to identify loci associated to this
      trait. RESULTS: We identified 4 single nucleotide polymorphisms with P<=5.0E-07
      and additional 119 ones with 5.0E-07<P<=5.0E-05. These markers were located
      throughout all chromosomes. The largest numbers were found on porcine chromosomes
      6 and 9 (n=15), 4 (n=13), and 7 (n=12) while the most significant marker was
      located on chromosome 18. Twenty-two single nucleotide polymorphisms were in
      intronic regions of genes already recognized by the Pre-Ensembl Sscrofa10.2
      assembly. Gene Ontology analysis indicated an enrichment of Gene Ontology terms
      associated with nervous system development and regulation in concordance with
      results of large genome wide association studies for human obesity. CONCLUSIONS:
      Further investigations are needed to evaluate the effects of the identified
      single nucleotide polymorphisms associated with backfat thickness on other traits
      as a pre-requisite for practical applications in breeding programs. Reported
      results could improve our understanding of the biology of fat metabolism and
      deposition that could also be relevant for other mammalian species including
      humans, confirming the role of neuronal genes on obesity.

PMID- 23153330
TI  - Conjugation of quinones with natural polyamines: toward an expanded
      antitrypanosomatid profile.
AB  - A combinatorial library of quinone-polyamine conjugates designed to optimize the
      antitrypanosomatid profile of hit compounds 1 and 2 has been prepared by a solid
      phase approach. The conjugates were evaluated against the three most important
      human trypanosomatid pathogens (Trypanosoma brucei rhodesiense, Trypanosoma
      cruzi, and Leishmania donovani), and several showed promising activity. A subset
      also inhibited trypanothione reductase in vitro and induced oxidase activity of
      the enzyme. A highly potent analogue (7) was identified with activity against T.
      brucei as low as 70 nM and a selectivity index of 72. Interestingly, the presence
      of a cadaverine tail confers to 7 the ability to target mitochondrial function in
      Leishmania. In fact, in L. donovani promastigotes, we verified for 7 a decrease
      of cytoplasmic ATP and mitochondrial potential. Therefore, the current results
      support the suitability of the conjugation approach for the development of novel
      polyamine conjugates with enhanced therapeutic potential.

PMID- 23153331
TI  - An exciting journey into excitability.

PMID- 23153332
TI  - The prognostic impact of epidermal growth factor receptor in patients with
      metastatic gastric cancer.
AB  - BACKGROUND: The epidermal growth factor receptor (EGFR) is a potential target of
      anticancer therapy in gastric cancer. However, its prognostic role in metastatic
      gastric or gastroesophageal junction (GE) cancer has not been established yet.
      METHODS: EGFR status was analyzed by immunohistochemistry (IHC) in paraffin
      embedded samples from 357 patients who received chemotherapy in 4 first-line
      trials. Automated RNA extraction from paraffin and RT-quantitative PCR were
      additionally used to evaluate EGFR mRNA expression in 130 patients. RESULTS: EGFR
      protein expression (any grade) and overexpression (3+) were observed in 43% and
      11% of patients, respectively. EGFR positivity correlated with intestinal type
      histology (p = 0.05), but not with other clinicopathologic characteristics.
      Median follow-up was 18.2 months. Median overall survival (OS) was similar in
      patients with EGFR positive vs. those with EGFR negative tumors, regardless
      whether positivity was defined as >=1+ (10.6 vs. 10.9 months, p = 0.463) or as 3+
      (8.6 vs. 10.8 months, p = 0.377). The multivariate analysis indicated that EGFR
      status is not an independent prognostic factor (hazard ratio 0.85, 0.56 to 1.12,
      p = 0.247). There were also no significant differences in overall survival when
      patients were categorized according to median (p = 0.116) or quartile (p = 0.767)
      distribution of EGFR mRNA gene expression. Similar distributions of progression
      free survival according to EGFR status were observed. CONCLUSIONS: Unlike
      different cancer types where EGFR-positive disease is associated with an adverse
      prognostic value, EGFR positivity is not prognostic of patient outcome in
      metastatic gastric or GE cancer.

PMID- 23153333
TI  - Measuring students' approaches to learning in different clinical rotations.
AB  - BACKGROUND: Many studies have explored approaches to learning in medical school,
      mostly in the classroom setting. In the clinical setting, students face different
      conditions that may affect their learning. Understanding students' approaches to
      learning is important to improve learning in the clinical setting. The aim of
      this study was to evaluate the Study Process Questionnaire (SPQ) as an instrument
      for measuring clinical learning in medical education and also to show whether
      learning approaches vary between rotations. METHODS: All students involved in
      this survey were undergraduates in their clinical phase. The SPQ was adapted to
      the clinical setting and was distributed in the last week of the clerkship
      rotation. A longitudinal study was also conducted to explore changes in learning
      approaches. RESULTS: Two hundred and nine students participated in this study
      (response rate 82.0%). The SPQ findings supported a two-factor solution involving
      deep and surface approaches. These two factors accounted for 45.1% and 22.5%,
      respectively, of the variance. The relationships between the two scales and their
      subscales showed the internal consistency and factorial validity of the SPQ to be
      comparable with previous studies. The clinical students in this study had higher
      scores for deep learning. The small longitudinal study showed small changes of
      approaches to learning with different rotation placement but not statistically
      significant. CONCLUSIONS: The SPQ was found to be a valid instrument for
      measuring approaches to learning among clinical students. More students used a
      deep approach than a surface approach. Changes of approach not clearly occurred
      with different clinical rotations.

PMID- 23153334
TI  - Mutational analysis of sulfite reductase hemoprotein reveals the mechanism for
      coordinated electron and proton transfer.
AB  - Sulfite reductase catalyzes the six-electron reduction of sulfite to sulfide. The
      active site, found in the hemoprotein subunit (SiRHP), sits on the distal face of
      a negatively charged porphyrinoid called siroheme whose central iron atom is
      coupled to a proximal Fe(4)S(4) cluster. Four positively charged amino acids are
      positioned around the active site cavity. Together, these two arginines (R83 and
      R153) and two lysines (K215 and K217) mitigate the negative charge on the
      siroheme macrocycle. They also serve as a cage around the distally bound anion
      that tightens when substrate binds and an active site loop clamps down.
      Structures of native SiRHP point to these amino acids as being important, but
      their specific roles are ill-defined. Here, we have altered those four active
      site amino acids and one amino acid on the flexible loop (N149) to probe their
      roles in SiRHP activity. None of these positively charged residues is required
      for electron transfer, but only R83S and N149W variants can produce a fully
      reduced product. By measuring the electrons used per unit of reduced sulfur
      released, we show that K215, R153, and K217 are responsible for intermediate and
      late proton transfers, whereas N149 and R153 play a role in the structure of the
      flexible loop that controls anion binding and release. R83 is primarily
      responsible for siroheme binding. Together, the activities and structures of
      these variants reveal specific roles for each in anion binding and in coupled
      proton transfer that facilitates electron transfer.

PMID- 23153336
TI  - Comparison of different amino-functionalization procedures on a selection of
      metal oxide microparticles: degree of modification and hydrolytic stability.
AB  - Amino-modified metal oxide materials are essential in a wide range of
      applications, including chromatography, ion adsorption, and as biomaterials. The
      aim of this study is to compare different functionalization techniques on a
      selection of metal oxides (SiO(2), TiO(2), ZrO(2), and SnO(2)) in order to
      determine which combination has the optimal properties for a certain application.
      We have used the nanocasting approach to synthesize micrometer-sized TiO(2),
      ZrO(2), and SnO(2) particles, which have similar morphologies and porosities as
      the starting mesoporous SiO(2) microparticles (Lichroprep Si 60). These metal
      oxides were subsequently functionalized by four different approaches, (a)
      covalent bonding of 3-aminopropyltriethoxysilane (APTES), (b) adsorption of 2
      aminoethyl dihydrogen phosphate (AEDP), (c) surface polymerization of aziridine
      (AZ), and (d) electrostatic interaction of poly(ethylenimine) (PEI), to produce a
      high surface coverage of amino groups on their surfaces. Scanning electron
      microscopy, nitrogen physisorption, and X-ray diffraction were used to
      characterize the unmodified metal oxide particles, while thermogravimetric
      analysis, ninhydrin adsorption, and zeta potential titrations were applied to
      gain insight into the successfulness of the various surface modifications.
      Finally, the hydrolytic stability at pH 2 and 10 was investigated by zeta
      potential measurements. Unfortunately, the AEDP approach was not able to produce
      efficient amino-modification on any of the tested metal oxide surfaces. On the
      other hand, modifications with APTES, aziridine, and PEI appeared to give fairly
      stable amino-functionalizations at high pH values for all metal oxides, while
      these modifications were easily detached at pH 2, with the exception of SnO(2),
      where the AZ and PEI samples were stable up to 40 h. The results are expected to
      give valuable insights into the possibility of replacing amino-modified silica
      with more hydrolytically stable metal oxides in various application fields, for
      example, chromatography and drug delivery.

PMID- 23153335
TI  - Spatial accessibility of primary health care utilising the two step floating
      catchment area method: an assessment of recent improvements.
AB  - BACKGROUND: The two step floating catchment area (2SFCA) method has emerged in
      the last decade as a key measure of spatial accessibility, particularly in its
      application to primary health care access. Many recent 'improvements' to the
      original 2SFCA method have been developed, which generally either account for
      distance-decay within a catchment or enable the usage of variable catchment
      sizes. This paper evaluates the effectiveness of various proposed methods within
      these two improvement groups. Moreover, its assessment focuses on how well these
      improvements operate within and between rural and metropolitan populations over
      large geographical regions. RESULTS: Demonstrating these improvements to the
      whole state of Victoria, Australia, this paper presents the first comparison
      between continuous and zonal (step) decay functions and specifically their effect
      within both rural and metropolitan populations. Especially in metropolitan
      populations, the application of either type of distance-decay function is shown
      to be problematic by itself. Its inclusion necessitates the addition of a
      variable catchment size function which can enable the 2SFCA method to dynamically
      define more appropriate catchments which align with actual health service supply
      and utilisation. CONCLUSION: This study assesses recent 'improvements' to the
      2SFCA when applied over large geographic regions of both large and small
      populations. Its findings demonstrate the necessary combination of both a
      distance-decay function and variable catchment size function in order for the
      2SFCA to appropriately measure healthcare access across all geographical regions.

PMID- 23153337
TI  - Induction of cognitive fatigue in MS patients through cognitive and physical
      load.
AB  - The objective of the study was to investigate whether cognitive fatigue in
      patients with multiple sclerosis (MS) is a spontaneous phenomenon or whether it
      can be provoked or exacerbated through cognitive effort and motor exercise.
      Thirty two patients with definite MS and cognitive fatigue according to the
      Fatigue Scale for Motor and Cognitive Functions (FSMC >= 22) performed attention
      tests (alertness, selective, and divided attention subtests from the TAP test
      battery for attention performance) twice during rest (baseline), and before and
      after treadmill training and cognitive load (a standardised battery of
      neuropsychological tests lasting 2.5 hours). Subjective exhaustion was assessed
      with a 10-point rating scale. Tonic alertness turned out to be the most sensitive
      test and showed significantly increased reaction times after treadmill training
      and after cognitive load. Patients' subjective assessment of exhaustion (10-point
      rating scale) and the objective test results were discrepant. In contrast,
      healthy control subjects (N = 20) did not show any decline of performance in the
      subtest alertness after cognitive or physical load. Data favour the concept that
      fatigue is induced by physical and mental load. Discrepancies between subjective
      and objective assessment offer therapeutic options. The common notion of a purely
      "subjective" lack of physical and/or mental energy should be reconsidered.

PMID- 23153338
TI  - Kinetic studies of Ni organic complexes using diffusive gradients in thin films
      (DGT) with double binding layers and a dynamic numerical model.
AB  - In situ deployments of diffusive gradients in thin films (DGT) can provide direct
      information on complex dissociation rates in natural waters. Recent advances in
      understanding the dynamics of the interactions of metal complexes within DGT
      devices have highlighted the characteristics of the binding layer, but there are
      few data to complement these theoretical developments. In this work the
      penetration into the Chelex binding layer of complexes of Ni with
      nitrilotriacetic (NTA) and Suwannee River fulvic and humic acids (FA and HA) in
      solution at pH 7 was investigated by deployment of DGT devices with two
      sequential binding layers, a "front" and a "back" layer. In Ni-NTA experiments,
      the masses of Ni bound by the front and back binding layers were similar, as
      predicted for slowly dissociating complexes. For Ni-FA/HA solutions, a higher
      mass of Ni was taken up by the front binding layer, consistent with fast
      dissociation from a high proportion of the binding sites. The ratio of Ni in the
      front to back binding layers was significantly lower (p < 0.05) for solutions of
      Ni-HA compared to those of Ni-FA, indicating that Ni-HA complexes are less labile
      than Ni-FA complexes in similar solutions (FA = 10 mg L(-1) and HA = 8 mg L(-1)).
      A dynamic numerical model of the complexes in a DGT system was used to estimate
      the dissociation rate constants that provided the best agreement with the
      experimental data. Values obtained of 2 +/- 0.5 * 10(-4) s(-1) for Ni-NTA and 2.5
      * 10(-3) s(-1) for Ni-FA when FA = 20 mg L(-1) and 3.42 * 10(-4) s(-1) for Ni-HA
      when HA = 8 mg L(-1), could be rationalized with current knowledge of the
      dynamics of these systems. This approach can improve kinetic information
      obtainable using DGT and widen the range of considered complex labilities.

PMID- 23153339
TI  - Thermodynamics-hydration relationships within loops that affect G-quadruplexes
      under molecular crowding conditions.
AB  - We systematically investigated the effects of loop length on the conformation,
      thermodynamic stability, and hydration of DNA G-quadruplexes under dilute and
      molecular crowding conditions in the presence of Na(+). Structural analysis
      showed that molecular crowding induced conformational switches of
      oligonucleotides with the longer guanine stretch and the shorter thymine loop.
      Thermodynamic parameters further demonstrated that the thermodynamic stability of
      G-quadruplexes increased by increasing the loop length from two to four, whereas
      it decreased by increasing the loop length from four to six. Interestingly, we
      found by osmotic pressure analysis that the number of water molecules released
      from the G-quadruplex decreased with increasing thermodynamic stability. We
      assumed that base-stacking interactions within the loops not only stabilized the
      whole G-quadruplex structure but also created hydration sites by accumulating
      nucleotide functional groups. The molecular crowding effects on the stability of
      G-quadruplexes composed of abasic sites, which reduce the stacking interactions
      at the loops, further demonstrated that G-quadruplexes with fewer stacking
      interactions within the loops released a larger number of water molecules upon
      folding. These results showed that the stacking interactions within the loops
      determined the thermodynamic stability and hydration of the whole G-quadruplex.

PMID- 23153340
TI  - Heart rate variability and target organ damage in hypertensive patients.
AB  - BACKGROUND: We evaluated the association between linear standard Heart Rate
      Variability (HRV) measures and vascular, renal and cardiac target organ damage
      (TOD). METHODS: A retrospective analysis was performed including 200 patients
      registered in the Regione Campania network (aged 62.4 +/- 12, male 64%). HRV
      analysis was performed by 24-h holter ECG. Renal damage was assessed by estimated
      glomerular filtration rate (eGFR), vascular damage by carotid intima-media
      thickness (IMT), and cardiac damage by left ventricular mass index. RESULTS:
      Significantly lower values of the ratio of low to high frequency power (LF/HF)
      were found in the patients with moderate or severe eGFR (p-value < 0.001).
      Similarly, depressed values of indexes of the overall autonomic modulation on
      heart were found in patients with plaque compared to those with a normal IMT (p
      value <0.05). These associations remained significant after adjustment for other
      factors known to contribute to the development of target organ damage, such as
      age. Moreover, depressed LF/HF was found also in patients with left ventricular
      hypertrophy but this association was not significant after adjustment for other
      factors. CONCLUSIONS: Depressed HRV appeared to be associated with vascular and
      renal TOD, suggesting the involvement of autonomic imbalance in the TOD. However,
      as the mechanisms by which abnormal autonomic balance may lead to TOD, and,
      particularly, to renal organ damage are not clearly known, further prospective
      studies with longitudinal design are needed to determine the association between
      HRV and the development of TOD.

PMID- 23153341
TI  - An interview with Lucio G. Costa and Michael Aschner, section editors for
      toxicology.
AB  - Lucio G. Costa is currently Professor of Environmental and Occupational Health
      Sciences at the School of Public Health at the University of Washington. Dr.
      Costa is a renowned neurotoxicologist whose research interests are focused on
      understanding the role of neurotoxic substances in neurodevelopmental disorders
      and other neurological, neuropsychiatric and neurodegenerative diseases. Dr
      Costa's research laboratory makes use of a variety of in vivo and in vitro cell
      culture systems, transgenic animal models and imaging techniques to study the
      cellular, biochemical and molecular mechanisms of neurotoxicity.Michael Aschner
      is the Gray E. B. Stahlman Professor of Pediatrics and Pharmacology at Vanderbilt
      University School of Medicine as well as a Senior Investigator at the Kennedy
      Center for Research on Human Development. Dr Aschner's research group has a
      particular interest in the neurobiology and physiology of astrocytes and the
      signaling mechanisms associated with central nervous system injury. Dr Aschner's
      laboratory studies metal uptake and distribution in the brain, investigating the
      mechanisms of transport of methylmercury and manganese across the capillaries of
      the blood-brain barrier. His research utilizes various experimental models (C.
      elegans, tissue cultures and rodents) to understand the acute toxicity of
      manganese deposition in the brains of human neonates.In this interview we find
      out a little more about the key issues in the field of toxicology research.

PMID- 23153343
TI  - Evidence about preventing cardiovascular disease.

PMID- 23153342
TI  - Photodynamic control of bioactivity in a nanofiber matrix.
AB  - Self-assembling peptide materials have been used extensively to mimic natural
      extracellular matrices (ECMs) by presenting bioactive epitopes on a synthetic
      matrix. Although this approach can facilitate a desired response from cells grown
      in the matrix, it lacks the capacity for spatial or temporal regulation of the
      presented signals. We describe here a photoresponsive, synthetic ECM using a
      supramolecular platform composed of peptide amphiphiles (PAs) that self-assemble
      into cylindrical nanofibers. A photocleavable nitrobenzyl ester group was
      included in the peptide backbone using a novel Fmoc-amino acid that is compatible
      with microwave-assisted solid-phase peptide synthesis. The placement of the
      photolabile group on the peptide backbone enabled efficient removal of the ECM
      derived cell adhesion epitope RGDS from PA molecules upon exposure to light (half
      life of photolysis ~1.9 min) without affecting the nanofiber assembly.
      Fibroblasts cultured on RGDS-presenting PA nanofiber substrates demonstrated
      increased cell spreading and more mature focal adhesions compared with
      unfunctionalized and control (RGES-presenting) surfaces, as determined by
      immunostaining and cell morphological analysis. Furthermore, we observed an
      arrest in fibroblast spreading on substrates containing a cleavable RGDS epitope
      when the culture was exposed to light; in contrast, this dynamic shift in cell
      response was absent when the RGDS epitope was attached to the PA molecule by a
      light-insensitive control linker. Light-responsive bioactive materials can
      contribute to the development of synthetic systems that more closely mimic the
      dynamic nature of native ECM.

PMID- 23153344
TI  - The effects of resistance training on cardiovascular disease risk factors in
      postmenopausal women: a randomized-controlled trial.
AB  - Our aim was to determine the effects of resistance training on cardiovascular
      risk factors in postmenopausal women. Forty-five women were included in the
      study. Resistance exercises were done with an intensity of 60% of 1-Repetition
      Maximum, for 12 weeks. Heart rate, blood pressure, estimated peak VO(2), lipid
      profiles, and homocysteine levels were evaluated. There were significant time and
      group interactions for body mass index (p = .02), heart rate (p = .04), systolic
      blood pressure (p = .03), estimated mean peak VO(2) (p = .00), and total
      cholesterol (p = .00), but there were no interactions with other evaluated
      parameters. Resistance training has beneficial effects on particular
      cardiovascular risk factors in postmenopausal women.

PMID- 23153345
TI  - Physical activity, weight, and waist circumference in midlife women.
AB  - During midlife years, women are at risk of increasing body weight and waist
      circumference. We evaluated changes in weight and waist circumference from
      enrollment to 2 years later and examined the influence of physical activity level
      on those changes among 232 women aged between 40 and 50. Weight increased
      significantly for the entire sample. Those who increased their physical activity
      from enrollment to 2 years later had the smallest increase in weight and had a
      slight decrease in waist circumference. To maintain ideal weight and waist
      circumference, midlife women should be encouraged to increase physical activity
      before and during the menopausal transition.

PMID- 23153346
TI  - Recovery of midlife women from myocardial infarction.
AB  - We conducted this qualitative study to elicit the experiences of midlife women
      who survived myocardial infarctions (MIs) and returned home to recover. We
      selected a phenomenological research method based on the philosophy of Merleau
      Ponty. The researcher interviewed eight women ranging in age from 45 to 65. The
      interviews were transcribed and analyzed using the approach of Thomas and Pollio.
      For the women in this study, figural themes of the experience of the MI and
      recovery must be understood within the existential grounds of the body and
      others. Themes included the following: (a) interference, (b) freedom/unfreedom,
      (c) knowing/not knowing, and (d) living in fear. Based on the findings of this
      study, we suggest that women need to be better educated before leaving the
      hospital. Returning home post MI was a difficult time, and the women in this
      study felt a support group for female MI survivors was needed.

PMID- 23153347
TI  - Qatari women living with cardiovascular diseases-challenges and opportunities to
      engage in healthy lifestyles.
AB  - In Qatar, cardiovascular diseases are the leading causes of morbidity and
      mortality. Cardiovascular diseases can be prevented and controlled by modifying
      lifestyle risk behaviors. In this qualitative study, we investigate ways to
      increase participation in physical activity, and to promote a healthy diet, and
      nonsmoking behavior in Qatari women. Individual in-depth interviews were
      conducted with 50 Arabic women. Participation in physical activity, observing a
      healthy diet, and abstinence from smoking are desirable lifestyle practices among
      Qatari women. Social support networks, cultural values, religion, changing
      sociodemographic and economic conditions, heart disease, and a harsh climate
      affect the ability of these women to pursue a healthy lifestyle.

PMID- 23153351
TI  - Higher-order aberrations and anisometropia.
AB  - PURPOSE/AIM: Myopia incidence is increasing around the world. Myopization is
      considered to be caused by a variety of factors. One consideration is whether
      higher-order aberrations (HOA) influence myopization. More knowledge of optics in
      anisometropic eyes might give further insight into the development of refractive
      error. MATERIALS AND METHODS: To analyze the possible influence of HOA on
      refractive error development, we compared HOA between anisometropes and
      isometropes. We analyzed HOA up to the 4th order for both eyes of 20
      anisometropes (mean age: 43 +/- 17 years) and 20 isometropes (mean age: 33 +/- 17
      years). HOA were measured with the Shack-Hartman i.Profiler (Carl Zeiss, Germany)
      and were recalculated for a 4 mm pupil. Mean spherical equivalent (MSE) was based
      on the subjective refraction. Anisometropia was defined as >=1 D interocular
      difference in MSE. The mean absolute differences between right and left eyes in
      spherical equivalent were 0.28 +/- 0.21 D in the isometropic group and 2.81 +/-
      2.04 D in the anisometropic group. Interocular differences in HOA were compared
      with the interocular difference in MSE using correlations. RESULTS: For
      isometropes oblique trefoil, vertical coma, horizontal coma and spherical
      aberration showed significant correlations between the two eyes. In
      anisometropes, all analyzed higher-order aberrations correlated significantly
      between the two eyes except oblique secondary astigmatism and secondary
      astigmatism. When analyzing anisometropes and isometropes separately, no
      significant correlations were found between interocular differences of higher
      order aberrations and MSE. For isometropes and anisometropes combined, tetrafoil
      correlated significantly with MSE in left eyes. CONCLUSIONS: The present study
      could not show that interocular differences of higher-order aberrations increase
      with increasing interocular difference in MSE.

PMID- 23153352
TI  - Horizontal relaxing incisions limit false positives in thick Mohs sections.

PMID- 23153353
TI  - Environmental health and household demographics impacting biosand filter
      maintenance and diarrhea in Guatemala: an application of structural equation
      modeling.
AB  - In rural health development practice, engineers and scientists must recognize the
      complex interactions that influence individuals' contact with disease-causing
      pathogens and understand how household habits may impact the adoption and long
      term sustainability of new technology. The goal of this study was to measure the
      effect of various environmental health factors and household demographics on the
      operation and maintenance of the Biosand filter (Centre for Affordable Water and
      Sanitation Technology, Calgary, Alberta, Canada) and diarrhea health burden in
      the region. In July and August 2010, randomized household surveys (n = 286) were
      completed in rural Guatemala detailing water access, sanitation availability,
      hygiene practice, socio-economic status, education level, filter operation and
      maintenance, and diarrhea health burden of the home. A hypothesized structural
      equation model was developed based on a review of published research and tested
      using the surveyed data. Model-derived parameter estimates indicated that: (a)
      proper personal hygiene practices significantly promote proper filter operation
      and maintenance; and (b) higher household education level, proper filter
      operation and maintenance, and improved water supply significantly reduce
      diarrhea health burden. Additionally, a high level of unexplained variance in
      diarrhea indicated the filter, though protective of health, is not the only
      factor influencing diarrhea.

PMID- 23153354
TI  - The role of outcome expectations in the generation of the feedback-related
      negativity.
AB  - The feedback-related negativity (FRN) is thought to index activity within the
      midbrain dopaminergic reward-learning system, with larger FRN magnitudes observed
      when outcomes are worse than expected. This view holds that the FRN is an index
      of neural activity coding for prediction errors, and reflects activity that can
      be used to adaptively alter future performance. Untested to date, however, is a
      key prediction of this view: the FRN should not appear in response to negative
      outcomes when outcome expectations are not allowed to develop. The current study
      tests this assumption by eliciting FRNs to win and loss feedback in conditions of
      participant choice, participant observation of computer choice, and, critically,
      simple presentation of win or loss feedback in the absence of a predictive choice
      cue. Whereas FRNs were observed in each of the conditions in which there was time
      for an expectation to develop, no FRN was observed in conditions without
      sufficient time for the development of an expectation. These results provide
      empirical support for an untested but central tenet of the reinforcement learning
      account of the genesis of the FRN.

PMID- 23153356
TI  - Construction of crystalline 2D covalent organic frameworks with remarkable
      chemical (acid/base) stability via a combined reversible and irreversible route.
AB  - Two new chemically stable [acid and base] 2D crystalline covalent organic
      frameworks (COFs) (TpPa-1 and TpPa-2) were synthesized using combined reversible
      and irreversible organic reactions. Syntheses of these COFs were done by the
      Schiff base reactions of 1,3,5-triformylphloroglucinol (Tp) with p
      phenylenediamine (Pa-1) and 2,5-dimethyl-p-phenylenediamine (Pa-2), respectively,
      in 1:1 mesitylene/dioxane. The expected enol-imine (OH) form underwent
      irreversible proton tautomerism, and only the keto-enamine form was observed.
      Because of the irreversible nature of the total reaction and the absence of an
      imine bond in the system, TpPa-1 and TpPa-2 showed strong resistance toward acid
      (9 N HCl) and boiling water. Moreover, TpPa-2 showed exceptional stability in
      base (9 N NaOH) as well.

PMID- 23153355
TI  - Concussive injury before or after controlled cortical impact exacerbates
      histopathology and functional outcome in a mixed traumatic brain injury model in
      mice.
AB  - Traumatic brain injury (TBI) may involve diverse injury mechanisms (e.g., focal
      impact vs. diffuse impact loading). Putative therapies developed in TBI models
      featuring a single injury mechanism may fail in clinical trials if the model does
      not fully replicate multiple injury subtypes, which may occur concomitantly in a
      given patient. We report development and characterization of a mixed
      contusion/concussion TBI model in mice using controlled cortical impact (CCI; 0.6
      mm depth, 6 m/sec) and a closed head injury (CHI) model at one of two levels of
      injury (53 vs. 83 g weight drop from 66 in). Compared with CCI or CHI alone,
      sequential CCI-CHI produced additive effects on loss of consciousness (p<0.001),
      acute cell death (p<0.05), and 12-day lesion size (p<0.05) but not brain edema or
      48-h contusion volume. Additive effects of CHI and CCI on post-injury motor
      (p<0.05) and cognitive (p<0.005) impairment were observed with sequential CCI-CHI
      (83 g). The data suggest that concussive forces, which in isolation do not induce
      histopathological damage, exacerbate histopathology and functional outcome after
      cerebral contusion. Sequential CHI-CCI may model complex injury mechanisms that
      occur in some patients with TBI and may prove useful for testing putative
      therapies.

PMID- 23153357
TI  - Mechanistic insights on organocatalytic enantioselective decarboxylative
      protonation by epicinchona-thiourea hybrid derivatives.
AB  - Mechanism and the origin of enantioselectivity in the decarboxylative protonation
      of alpha-amino malonate hemiester promoted by epicinchona-thiourea hybrid
      organocatalyst is established by using the DFT(M06-2X/6-311+G**//ONIOM2)
      computational methods. The origin of stereoselectivity rendered by this hybrid
      bifunctional catalyst in asymmetric protonation is investigated for the first
      time using suitable transition-state models. A detailed conformational analysis
      of N-[3,5-bis(trifluoromethyl)]phenylthiourea-based epicinchonidine reveals the
      potential for a bifunctional mode of activation of the substrate alpha-amino
      malonate hemiester through hydrogen bonding. Six different conformer families
      differing in characteristic dihedral angles are identified within a range of 16
      kcal/mol with respect to the lowest energy conformer. Different likely
      mechanistic pathways obtained through detailed analysis of the transition states
      and intermediates are compared. It is identified that in the preferred pathway,
      the decarboxylation is followed by a direct proton transfer from the chiral
      quinuclidinium moiety to the enolate carbon as opposed to a conventional
      protonation at the enolate oxygen followed by a keto-enol tautomerization. The
      factors responsible for high levels of observed stereoselectivity are traced to
      interesting hydrogen-bonding interactions offered by the thiourea-cinchona
      bifunctional framework. The predicted stereoselectivities using computed Gibbs
      free energies of diastereomeric transition states are in fair agreement with the
      experimental stereoselectivities.

PMID- 23153358
TI  - The Alberta moving beyond breast cancer (AMBER) cohort study: a prospective study
      of physical activity and health-related fitness in breast cancer survivors.
AB  - BACKGROUND: Limited research has examined the association between physical
      activity, health-related fitness, and disease outcomes in breast cancer
      survivors. Here, we present the rationale and design of the Alberta Moving Beyond
      Breast Cancer (AMBER) Study, a prospective cohort study designed specifically to
      examine the role of physical activity and health-related fitness in breast cancer
      survivorship from the time of diagnosis and for the balance of life. The AMBER
      Study will examine the role of physical activity and health-related fitness in
      facilitating treatment completion, alleviating treatment side effects, hastening
      recovery after treatments, improving long term quality of life, and reducing the
      risks of disease recurrence, other chronic diseases, and premature death.
      METHODS/DESIGN: The AMBER Study will enroll 1500 newly diagnosed, incident, stage
      I-IIIc breast cancer survivors in Alberta, Canada over a 5 year period.
      Assessments will be made at baseline (within 90 days of surgery), 1 year, and 3
      years consisting of objective and self-reported measurements of physical
      activity, health-related fitness, blood collection, lymphedema, patient-reported
      outcomes, and determinants of physical activity. A final assessment at 5 years
      will measure patient-reported data only. The cohort members will be followed for
      an additional 5 years for disease outcomes. DISCUSSION: The AMBER cohort will
      answer key questions related to physical activity and health-related fitness in
      breast cancer survivors including: (1) the independent and interactive
      associations of physical activity and health-related fitness with disease
      outcomes (e.g., recurrence, breast cancer-specific mortality, overall survival),
      treatment completion rates, symptoms and side effects (e.g., pain, lymphedema,
      fatigue, neuropathy), quality of life, and psychosocial functioning (e.g.,
      anxiety, depression, self-esteem, happiness), (2) the determinants of physical
      activity and health-related fitness including demographic, medical, social
      cognitive, and environmental variables, (3) the mediators of any observed
      associations between physical activity, health-related fitness, and health
      outcomes including biological, functional, and psychosocial, and (4) the
      moderators of any observed associations including demographic, medical, and
      biological/disease factors. Taken together, these data will provide a
      comprehensive inquiry into the outcomes, determinants, mechanisms, and moderators
      of physical activity and health-related fitness in breast cancer survivors.

PMID- 23153359
TI  - Wanted: role models--medical students' perceptions of professionalism.
AB  - BACKGROUND: Transformation of medical students to become medical professionals is
      a core competency required for physicians in the 21st century. Role modeling was
      traditionally the key method of transmitting this skill. Medical schools are
      developing medical curricula which are explicit in ensuring students develop the
      professional competency and understand the values and attributes of this role.
      The purpose of this study was to determine student perception of professionalism
      at the University of Ottawa and gain insights for improvement in promotion of
      professionalism in undergraduate medical education. METHODS: Survey on student
      perception of professionalism in general, the curriculum and learning environment
      at the University of Ottawa, and the perception of student behaviors, was
      developed by faculty and students and sent electronically to all University of
      Ottawa medical students. The survey included both quantitative items including an
      adapted Pritzker list and qualitative responses to eight open ended questions on
      professionalism at the Faculty of Medicine, University of Ottawa. All analyses
      were performed using SAS version 9.1 (SAS Institute Inc. Cary, NC, USA). Chi
      square and Fischer's exact test (for cell count less than 5) were used to derive
      p-values for categorical variables by level of student learning. RESULTS: The
      response rate was 45.6% (255 of 559 students) for all four years of the
      curriculum. 63% of the responses were from students in years 1 and 2
      (preclerkship). Students identified role modeling as the single most important
      aspect of professionalism. The strongest curricular recommendations included
      faculty-led case scenario sessions, enhancing interprofessional interactions and
      the creation of special awards to staff and students to "celebrate"
      professionalism. Current evaluation systems were considered least effective. The
      importance of role modeling and information on how to report lapses and breaches
      was highlighted in the answers to the open ended questions. CONCLUSIONS: Students
      identify the need for strong positive role models in their learning environment,
      and for effective evaluation of the professionalism of students and teachers.
      Medical school leaders must facilitate development of these components within the
      MD education and faculty development programs as well as in clinical milieus
      where student learning occurs.

PMID- 23153361
TI  - Hydration shell parameters of aqueous alcohols: THz excess absorption and packing
      density.
AB  - Solvation in water requires minimizing the perturbations in its hydrogen bonded
      network. Hence solutes distort water molecular motions in a surrounding domain,
      forming a molecule-specific hydration shell. The properties of those hydration
      shells impact the structure and function of the solubilized molecules, both at
      the single molecule and at higher order levels. The size of the hydration shell
      and the picoseconds time-scale water dynamics retardation are revealed by
      terahertz (THz) absorption coefficient measurements. Room-temperature absorption
      coefficient at f = 0.28 [THz] is measured as a function of alcohol concentration
      in aqueous methanol, ethanol, 1,2-propanol, and 1-butanol solutions. Highly
      diluted alcohol measurements and enhanced overall measurement accuracy are
      achieved with a THz absorption measurement technique of nL-volume liquids in a
      capillary tube. In the absorption analysis, bulk and interfacial molecular
      domains of water and alcohol are considered. THz ideal and excess absorption
      coefficients are defined in accordance with thermodynamics mixing formulations.
      The parameter extraction method is developed based on a THz excess absorption
      model and hydrated solute molecule packing density representation. First, the
      hydration shell size is deduced from the hydrated solute packing densities at two
      specific THz excess absorption nonlinearity points: at infinite alcohol dilution
      (IAD) and at the THz excess absorption extremum (EAE). Consequently, interfacial
      water and alcohol molecular domain absorptions are deduced from the THz excess
      absorption model. The hydration shell sizes obtained at the THz excess absorption
      extremum are in excellent agreement with other reports. The hydration shells of
      methanol, ethanol, 1- and 2-propanol consist of 13.97, 22.94, 22.99, and 31.10
      water molecules, respectively. The hydration shell water absorption is on average
      0.774 +/- 0.028 times the bulk water absorption. The hydration shell parameters
      might shed light on hydration dynamics of biomolecules.

PMID- 23153360
TI  - The impact of insecticide-treated school uniforms on dengue infections in school
      aged children: study protocol for a randomised controlled trial in Thailand.
AB  - BACKGROUND: There is an urgent need to protect children against dengue since this
      age group is particularly sensitive to the disease. Since dengue vectors are
      active mainly during the day, a potential target for control should be schools
      where children spend a considerable amount of their day. School uniforms are the
      cultural norm in most developing countries, worn throughout the day. We
      hypothesise that insecticide-treated school uniforms will reduce the incidence of
      dengue infection in school-aged children. Our objective is to determine the
      impact of impregnated school uniforms on dengue incidence. METHODS: A randomised
      controlled trial will be conducted in eastern Thailand in a group of schools with
      approximately 2,000 students aged 7-18 years. Pre-fabricated school uniforms will
      be commercially treated to ensure consistent, high-quality insecticide
      impregnation with permethrin. A double-blind, randomised, crossover trial at the
      school level will cover two dengue transmission seasons. DISCUSSION: Practical
      issues and plans concerning intervention implementation, evaluation, analysing
      and interpreting the data, and possible policy implications arising from the
      trial are discussed. TRIAL REGISTRATION: clinicaltrial.gov. REGISTRATION NUMBER:
      NCT01563640.

PMID- 23153362
TI  - Northern = smart and Southern = nice: the development of accent attitudes in the
      United States.
AB  - Adults evaluate others based on their speech, yet little is known of the
      developmental trajectory by which accent attitudes are acquired. Here we
      investigate the development of American children's attitudes about Northern- and
      Southern-accented American English. Children in Illinois (the "North") and
      Tennessee (the "South") evaluated the social desirability, personality
      characteristics, and geographic origins of Northern- and Southern-accented
      individuals. Five- to 6-year-old children in Illinois preferred the Northern
      accented speakers as potential friends, yet did not demonstrate knowledge of any
      stereotypes about the different groups; 5-6-year-old children in Tennessee did
      not show a preference towards either type of speaker. Nine- to 10-year-old
      children in both Illinois and Tennessee evaluated the Northern-accented
      individuals as sounding "smarter" and "in charge", and the Southern-accented
      individuals as sounding "nicer." Thus, older children endorse similar stereotypes
      to those observed in adulthood. These accent attitudes develop in parallel across
      children in different regions and reflect both positive and negative assessments
      of a child's own group.

PMID- 23153363
TI  - Dihydrotestosterone induces SREBP-1 expression and lipogenesis through the
      phosphoinositide 3-kinase/Akt pathway in HaCaT cells.
AB  - BACKGROUND: The purpose of this study was to investigate the effects and
      mechanisms of dihydrotestosterone (DHT)-induced expression of sterol regulatory
      element binding protein-1 (SREBP-1), and the synthesis and secretion of lipids,
      in HaCaT cells. HaCaT cells were treated with DHT and either the phosphoinositide
      3-kinase inhibitor LY294002 or the extracellular-signal-regulated kinase (ERK)
      inhibitor PD98059. Real time-PCR, Western blot, Oil Red staining and flow
      cytometry were employed to examine the mRNA and protein expressions of SREBP-1,
      the gene transcription of lipid synthesis, and lipid secretion in HaCaT cells.
      FINDINGS: We found that DHT upregulated mRNA and protein expressions of SREBP-1.
      DHT also significantly upregulated the transcription of lipid synthesis-related
      genes and increased lipid secretion, which can be inhibited by the addition of
      LY294002. CONCLUSIONS: Collectively, these results indicate that DHT induces
      SREBP-1 expression and lipogenesis in HaCaT cells via activation of the
      phosphoinositide 3-kinase/Akt Pathway.

PMID- 23153364
TI  - The complete swine olfactory subgenome: expansion of the olfactory gene
      repertoire in the pig genome.
AB  - BACKGROUND: Insects and animals can recognize surrounding environments by
      detecting thousands of chemical odorants. Olfaction is a complicated process that
      begins in the olfactory epithelium with the specific binding of volatile odorant
      molecules to dedicated olfactory receptors (ORs). OR proteins are encoded by the
      largest gene superfamily in the mammalian genome. RESULTS: We report here the
      whole genome analysis of the olfactory receptor genes of S. scrofa using
      conserved OR gene specific motifs and known OR protein sequences from diverse
      species. We identified 1,301 OR related sequences from the S. scrofa genome
      assembly, Sscrofa10.2, including 1,113 functional OR genes and 188 pseudogenes.
      OR genes were located in 46 different regions on 16 pig chromosomes. We
      classified the ORs into 17 families, three Class I and 14 Class II families, and
      further grouped them into 349 subfamilies. We also identified inter- and intra
      chromosomal duplications of OR genes residing on 11 chromosomes. A significant
      number of pig OR genes (n = 212) showed less than 60% amino acid sequence
      similarity to known OR genes of other species. CONCLUSION: As the genome assembly
      Sscrofa10.2 covers 99.9% of the pig genome, our analysis represents an almost
      complete OR gene repertoire from an individual pig genome. We show that S. scrofa
      has one of the largest OR repertoires, suggesting an expansion of OR genes in the
      swine genome. A significant number of unique OR genes in the pig genome may
      suggest the presence of swine specific olfactory stimulation.

PMID- 23153365
TI  - Activation of Rac1-dependent redox signaling is critically involved in
      staurosporine-induced neurite outgrowth in PC12 cells.
AB  - Staurosporine, a non-specific protein kinase inhibitor, has been shown to induce
      neurite outgrowth in PC12 cells, but the mechanism by which staurosporine induces
      neurite outgrowth is still obscure. In the present study, we investigated whether
      the activation of Rac1 was responsible for the neurite outgrowth triggered by
      staurosporine. Staurosporine caused rapid neurite outgrowth independent of the
      ERK signaling pathways. In contrast, neurite outgrowth in response to
      staurosporine was accompanied by activation of Rac1, and the Rac1 inhibitor
      NSC23766 attenuated the staurosporine-induced neurite outgrowth in a
      concentration-dependent manner. In addition, suppression of Rac1 activity by
      expression of the dominant negative mutant Rac1N17 also blocked the staurosporine
      induced morphological differentiation of PC12 cells. Staurosporine caused an
      activation of NADPH oxidase and increased the production of reactive oxygen
      species (ROS), which was prevented by NSC23766 and diphenyleneiodonium (DPI), an
      NADPH oxidase inhibitor. Staurosporine-induced neurite outgrowth was attenuated
      by pretreatment with DPI and exogenous addition of sublethal concentration of
      H2O2 accelerated neurite outgrowth triggered by staurosporine. These results
      indicate that activation of Rac1, which leads to ROS generation, is required for
      neurite outgrowth induced by staurosporine in PC12 cells.

PMID- 23153366
TI  - Neuroimaging features of C9ORF72 expansion.
AB  - Hexanucleotide expansion intronic to chromosome 9 open reading frame 72 (C9ORF72)
      has recently been identified as the most common genetic cause of both familial
      and sporadic amyotrophic lateral sclerosis and of frontotemporal dementia with or
      without concomitant motor neuron disease. Given the common frequency of this
      genetic aberration, clinicians seek to identify neuroimaging hallmarks
      characteristic of C9ORF72-associated disease, both to provide a better
      understanding of the underlying degenerative patterns associated with this
      mutation and to enable better identification of patients for genetic screening
      and diagnosis. A survey of the literature describing C9ORF72 neuroimaging thus
      far suggests that patients with this mutation may demonstrate symmetric frontal
      and temporal lobe, insular, and posterior cortical atrophy, although temporal
      involvement may be less than that seen in other mutations. Some studies have also
      suggested cerebellar and thalamic involvement in C9ORF72-associated disease.
      Diffuse cortical atrophy that includes anterior as well as posterior structures
      and subcortical involvement thus may represent unique features of C9ORF72. 

PMID- 23153367
TI  - Free-Wilson and structural approaches to co-optimizing human and rodent isoform
      potency for 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) inhibitors.
AB  - 11beta-Hydroxysteroid dehydrogenase 1 (11beta-HSD1) has been a target of
      intensive research efforts across the pharmaceutical industry, due to its
      potential for the treatment of type II diabetes and other elements of the
      metabolic syndrome. To demonstrate the value of 11beta-HSD1 in preclinical
      models, we required inhibitors with good potency against both human and rodent
      isoforms. Herein, we describe our efforts to understand how to co-optimize human
      and murine potency within the (5-hydroxy-2-adamantyl)-pyrimidine-5-carboxamide
      series. Two approaches are described-a data-driven (Free-Wilson) analysis and a
      structure-based design approach. The conclusions from these approaches were used
      to inform an efficient campaign to design compounds with consistently good
      human/murine potency within a logD(7.4) range of 1-3. Compounds 20 and 26
      demonstrated good rodent PK, which allowed us to demonstrate a PK/PD relationship
      in rat and mouse. We then evaluated 26 against glycemic and body weight end
      points in murine disease models, where it demonstrated glucose and body weight
      efficacy at 300 mg/kg/day but only body weight efficacy at 50 mg/kg/day, despite
      providing >90% target engagement in the liver.

PMID- 23153368
TI  - Electrocardiographic P-wave characteristics in patients with psoriasis vulgaris.
AB  - PURPOSE: Psoriasis vulgaris is one of the most common skin disorders. Patients
      with psoriasis carry an excessive risk of atrial fibrillation (AF). The
      differences between the maximum (Pmax) and the minimum (Pmin) P-wave duration on
      ECG are defined as P-wave dispersion (PWD). Prolongation of PWD is an independent
      risk factor for the development of AF. The aim of this the study was to
      investigate P-wave duration and PWD in patients with psoriasis. METHODS: Sixty
      one adult patients with psoriasis vulgaris (group 1) and 58 age and sex-matched
      healthy individuals (group 2) were included in this study. ECG recordings were
      obtained, and the P-wave variables were calculated. Results were reported as mean
      +/- standard deviation and percentages. Continuous variables were analysed using
      Student's t test. A value of P < 0.05 was considered statistically significant.
      RESULTS: Pmax and PWD were significantly higher in group 1 than in group 2 (108.8
      +/- 21.3 ms versus 93.3 +/- 13.0 ms, P < 0.001; 67.4 +/- 22.9 ms versus 45.0 +/-
      19.6 ms, P < 0.001, respectively). Also, Pmin was significantly lower in group 1
      (41.3 +/- 12.3 ms versus 48.3 +/- 14.3 ms, P = 0.04). The psoriasis disease
      activity score and hsCRP correlated with PWD (P < 0.01). CONCLUSIONS: Atrial
      conduction of sinus impulses was impaired in patients with psoriasis vulgaris. It
      was more prominent in patients with severe disease. Physicians caring for
      patients with psoriasis vulgaris should screen them for AF development.

PMID- 23153369
TI  - The SIDS--critical diaphragm failure hypothesis revisited.

PMID- 23153370
TI  - Immobilizing performances, comfort, and user-friendliness of the shoulder
      abduction-external rotation braces.
AB  - BACKGROUND: Shoulder external rotation braces used for patients with a first-time
      shoulder dislocation are designed with a variety of arm positions in abduction as
      well as external rotation. However, few studies have focused on their
      immobilizing performance, comfort, or user-friendliness. Especially, there have
      been no robust data of shoulder abduction-external rotation (A-ER) braces in
      comparison to those of external rotation (ER) braces. METHODS: Four types of
      commercially available shoulder braces (two ER and two A-ER braces) were tested
      in 30 healthy participants. The angles of external rotation and abduction were
      measured for each brace at initial application, after simulated daily activities,
      and after reapplication. Then, subjects were asked to assess the discomfort of
      bracing and difficulty of reapplication using a visual analogue scale. Data were
      compared between the two ER braces and two A-ER braces as well as among the four
      braces. RESULTS: For both external rotation angle and subjective assessment,
      there were no significant differences between the ER and A-ER braces. Among the
      four braces, the measurement of arm position demonstrated no significant
      differences, except the external rotation angles between the two ER braces. The A
      ER braces were assessed to be significantly less comfortable than the ER braces
      in the subjective assessment. CONCLUSIONS: Immobilization using the A-ER braces
      could maintain the arm position in abduction-external rotation with comparable
      user-friendliness, although they tended to be less comfortable during daily
      activities compared to the ER braces.

PMID- 23153371
TI  - Prevalence and severity of atherosclerosis in extra cranial carotid arteries in
      Nigeria: an autopsy study.
AB  - BACKGROUND: There has been a paucity of autopsy studies on atherosclerotic
      lesions in Nigerians, the last one conducted at our centre being more than four
      decades ago. There has also been considerable epidemiological transition. The
      objective of the study was to determine the frequency, severity, pattern and
      distribution of atherosclerotic lesions in extra cranial carotid arteries (ECCA)
      in Nigerians at autopsy. METHODS: ECCA of 30 consecutive Nigerian patients
      undergoing autopsy at a University teaching hospital were examined using the
      American Heart Association (AHA) histological grading and classification of
      atherosclerosis. RESULTS: Atherosclerotic lesions of ECCA were present in 73.3%
      of the subjects with the right and the left carotid bifurcations (28.3%) being
      the most frequently affected sites. Using the AHA classification of
      atherosclerosis, a total of 176(73.3%) lesions were found in the 240 histological
      sections of blood vessels examined. Of these, 22.5% were types I, 22.5% were
      types II, 15.4% were type V, and 7.5% were type III. The VII to type IX lesions
      were rare. When these atherosclerotic lesions were grouped into mild, moderate
      and severe, 52.5% were mild lesions (types I-III); 18.3% were moderate lesions
      (types IV and V); and 2.5% were severe lesions (types VI to IX). The severe
      lesions were most frequently observed in the left carotid bifurcation (50%) and
      they first appeared in the age group 45-49 years. Age, hypertension and diabetes
      mellitus were strong risk factors for atherosclerosis. CONCLUSIONS: Compared with
      four decades ago there has been an apparent increase in severity and extent of
      ECCA atherosclerosis especially after the age of 45 years in autopsies from our
      centre. This change in the amount of atherosclerosis over time is possibly due to
      the epidemiologic transition. This may worsen the rise in stoke incidence within
      this community and as such, great effort should be made to follow-up and manage
      CVD risk factors within the community.

PMID- 23153372
TI  - Formation of iron(III) (hydr)oxides on polyaspartate- and alginate-coated
      substrates: effects of coating hydrophilicity and functional group.
AB  - To better understand the transport of contaminants in aqueous environments, we
      need more accurate information about heterogeneous and homogeneous nucleation of
      iron(III) hydroxide nanoparticles in the presence of organics. We combined
      synchrotron-based grazing incidence small-angle X-ray scattering (GISAXS) and
      SAXS and other nanoparticle and substrate surface characterization techniques to
      observe iron(III) (hydr)oxide [10-4 M Fe(NO3)3 in 10 mM NaNO3] precipitation on
      quartz and on polyaspartate- and alginate-coated glass substrates and in solution
      (pH = 3.7 +/- 0.2). Polyaspartate was determined to be the most negatively
      charged substrate and quartz the least; however, after 2 h, total nanoparticle
      volume calculations--from GISAXS--indicate that positively charged precipitation
      on quartz is twice that of alginate and 10 times higher than on polyaspartate,
      implying that electrostatics do not govern iron(III) (hydr)oxide nucleation. On
      the basis of contact angle measurements and surface characterization, we
      concluded that the degree of hydrophilicity may control heterogeneous nucleation
      on quartz and organic-coated substrates. The arrangement of functional groups at
      the substrate surface (--OH and --COOH) may also contribute. These results
      provide new information for elucidating the effects of polymeric organic
      substrate coatings on the size, volume, and location of nucleating iron
      hydroxides, which will help predict nanoparticle interactions in natural and
      engineered systems.

PMID- 23153373
TI  - Microfluidic fabrication and thermoreversible response of core/shell photonic
      crystalline microspheres based on deformable nanogels.
AB  - Soft photonic crystals (PC) are more appealing due to the responsiveness of the
      building blocking-deformable nanoparticles to the external stimuli. In this
      report, we demonstrate, for the first time, the generation of soft core/shell PC
      microspheres through a combination of a microfluidic technique, encapsulation of
      well-ordered temperature responsive polymer nanogels suspension, and
      photopolymerization of a transparent shell resin. This strategy not only ensures
      the monodispersity of core/shell PC microspheres, but also precisely controls
      their size, shell thickness, and optical properties by simply adjusting the flow
      rate ratio and mass fraction of the nanogels. More interestingly, the intensity
      of the reflection spectra of the crystalline nanogel arrays in the core can be
      modulated reversibly by controlling the shell thickness or the temperature. As a
      result of their symmetric structure, the resulting PC microspheres exhibited
      excellent structural colors and photonic band gaps for normal incident light
      independent of the position on the spherical surface. Multifunctional PC
      microspheres can also be generated by simply dispersing functional species
      together with the nanogels. This core/shell PC microsphere with tunable shell
      thickness and reversible thermoresponse could be significant for potential
      applications in the fields of chemical/biological sensors, display, encoding, and
      optical switching.

PMID- 23153374
TI  - Graphene/single-walled carbon nanotube hybrids: one-step catalytic growth and
      applications for high-rate Li-S batteries.
AB  - The theoretically proposed graphene/single-walled carbon nanotube (G/SWCNT)
      hybrids by placing SWCNTs among graphene planes through covalent C-C bonding are
      expected to have extraordinary physical properties and promising engineering
      applications. However, the G/CNT hybrids that have been fabricated differ greatly
      from the proposed G/SWCNT hybrids because either the covalent C-C bonding is not
      well constructed or only multiwalled CNTs/carbon nanofibers rather than SWCNTs
      are available in the hybrids. Herein, a novel G/SWCNT hybrid was successfully
      fabricated by a facile catalytic growth on layered double hydroxide (LDH) at a
      high temperature over 950  degrees C. The thermally stable Fe nanoparticles and
      the uniform structure of the calcined LDH flakes are essential for the
      simultaneously catalytic deposition of SWCNTs and graphene. The SWCNTs and the
      CVD-grown graphene, as well as the robust connection between the SWCNTs and
      graphene, facilitated the construction of a high electrical conductive pathway.
      The internal spaces between the two stacked graphene layers and among SWCNTs
      offer room for sulfur storage. Therefore, the as obtained G/SWCNT-S cathode
      exhibited excellent performance in Li-S batteries with a capacity as high as 650
      mAh g(-1) after 100 cycles even at a high current rate of 5 C. Such a novel
      G/SWCNT hybrid can serve not only as a prototype to shed light on the chemical
      principle of G/CNT synthesis but also as a platform for their further
      applications in the area of nanocomposites, heterogeneous catalysis, drug
      delivery, electrochemical energy storage, and so on.

PMID- 23153375
TI  - The reconstruction of two large full-thickness wounds of the upper lip with
      different operative techniques: when possible, a local flap repair is preferable
      to reconstruction with free tissue transfer.
AB  - BACKGROUND: Large full-thickness wounds of the upper lip are often referred to
      operating room-based surgeons for repair given the perceived difficulties in
      restoring upper lip form and function with simpler operative techniques.
      OBJECTIVE: To illustrate the functional, aesthetic, and cost differences between
      two techniques used to repair full-thickness wounds of the upper lip. MATERIALS
      AND METHODS: Two patients with difficult full-thickness wounds of the majority of
      the upper lip were reviewed. One patient underwent reconstruction with a
      composite free flap in an operating room, and one underwent repair using local
      tissue rearrangement using bilateral modified nasolabial flaps in an outpatient
      setting. RESULTS: Both patients were adequately reconstructed, but the patient
      repaired using local tissue rearrangement had a better aesthetic outcome and
      superior preservation of oral competency. In addition, the costs of this
      patient's reconstructive care were less than 2.4% of the costs of the care of the
      patient repaired using a free flap. CONCLUSION: When possible, large, full
      thickness wounds of the upper lip should be repaired with local tissue
      rearrangement in an outpatient setting to offer patients potential improvements
      in functional and aesthetic outcomes while minimizing treatment costs.

PMID- 23153376
TI  - Duplex destabilization by four ribosomal DEAD-box proteins.
AB  - DEAD-box proteins are believed to participate in the folding of RNA by
      destabilizing RNA secondary or tertiary structures. Although these proteins bind
      and hydrolyze ATP, the mechanism by which nucleotide hydrolysis is coupled to
      helix destabilization may vary among different DEAD-box proteins. To investigate
      their abilities to disrupt helices and couple ATP hydrolysis to unwinding, we
      assayed the Saccharomyces cerevisiae ribosomal DEAD-box proteins, Dbp3p, Dbp4p,
      Rok1p, and Rrp3p utilizing a series of RNA substrates containing a short duplex
      and either a 5' or 3' single-stranded region. All four proteins unwound a 10 bp
      helix in vitro in the presence of ATP; however, significant dissociation of
      longer helices was not observed. While Dbp3p did not require a single-stranded
      extension to disrupt a helix, the unwinding activities of Dbp4p, Rok1p, and Rrp3p
      were substantially stimulated by either a 5' or 3' single-stranded extension.
      Interestingly, these proteins showed a clear length dependency with 3' extensions
      that was not observed with 5' extensions, suggesting that they bind substrates
      with a preferred orientation. In the presence of AMPPNP or ADP, all four proteins
      displayed displacement activity suggesting that nucleotide binding is sufficient
      to facilitate duplex disruption. Further enhancement of the strand displacement
      rate in the presence of ATP was observed for only Dbp3p and Rrp3p.

PMID- 23153377
TI  - Pyrethroid pesticide exposure and risk of childhood acute lymphocytic leukemia in
      Shanghai.
AB  - Significant amounts of pyrethroid pesticides are used throughout China. Previous
      studies have suggested that exposure to pesticides may increase the risk of
      childhood cancer; however, few studies have focused on pyrethroid metabolites. We
      investigated five nonspecific metabolites of pyrethroid pesticides found in
      children's urine and examined the correlation with childhood leukemia. We
      conducted a hospital-based case-control study of childhood acute lymphocytic
      leukemia (ALL) in Shanghai between 2010 and 2011. The study included 176 children
      aged 0-14 years and 180 controls matched for age and sex. Compared with those in
      the lowest quartiles of total and individual metabolites, the highest quartiles
      were associated with an approximate 2-fold increased risk of ALL [total
      metabolites: odds ratio (OR) = 2.75, 95% confidence interval (CI), 1.43-5.29; cis
      DCCA: OR = 2.21, 95% CI, 1.16-4.19; trans-DCCA: OR = 2.33, 95% CI, 1.23-4.41; and
      3-PBA: OR = 1.84, 95% CI, 1.00-3.38], and most of the positive trends were
      significant (p < 0.05). Our findings suggest that urinary levels of pyrethroid
      metabolites may be associated with an elevated risk of childhood ALL and
      represent a previously unreported quantitative exposure assessment for childhood
      leukemia.

PMID- 23153378
TI  - Comparing P300 modulations: target-to-target interval versus infrequent nontarget
      to-nontarget interval in a three-stimulus task.
AB  - This study examined temporal determinants of the P300 component of the ERP in a
      three-stimulus visual oddball task. Frequent standards, with equiprobable targets
      and infrequent nontargets, were utilized. We tested whether the infrequent
      nontarget-to-nontarget interval (infrequent NNI) influences P300 amplitudes and
      latencies analogously to the target-to-target interval (TTI). EEG was recorded
      from 27 participants, and response time and P300 effects of TTIs and infrequent
      NNIs were assessed. Increases in TTI augmented target P300 amplitudes and
      decreased latencies and response times. However, this modulation of P300
      amplitude was weak for manipulations of infrequent NNI. P300 latencies increased
      initially before decreasing across infrequent NNI levels. Together, these
      findings support the notion that the P300 has an underlying temporal mechanism
      that is modulated by motivationally significant events. Theoretical implications
      are discussed.

PMID- 23153379
TI  - Benefits of hyperthermic intraperitoneal chemotherapy for patients with serosal
      invasion in gastric cancer: a meta-analysis of the randomized controlled trials.
AB  - BACKGROUND: In this meta-analysis we aimed to determine the effectiveness and
      safety of hyperthermic intraperitoneal chemotherapy (HIPC) for patients with
      advanced gastric cancer who underwent gastrectomy. METHODS: In accordance with
      standard meta-analysis procedures, our study included patients who underwent
      resection for advanced gastric cancer and were randomly allocated to receive
      either hyperthermic intraperitoneal chemotherapy or control. We searched PubMed
      (up to November 2011), EMBASE (up to November 2011), Cochrane Database of
      Systematic Reviews (CDSR), and Cochrane Central Register of Controlled Trials
      (CCTR) (up to November 2011). Both published and unpublished trials were included
      in the analysis, and no search restrictions were imposed. There was no language
      restriction. The results were analyzed using RevMan 5.1 software, which was
      provided by Cochrane Collaboration. RESULTS: There were ten randomized controlled
      trials included in the analysis. A total of 1062 patients with gastric cancer in
      these studies were divided into the HIPC group (n = 518) and control group (n =
      544). A significant improvement in survival was observed in the HIPC groups
      compared to the control group in the mitomycin C (MMC) subgroup (RR = 0.75, 95%CI
      0.65-0.86; P < 0.00001) and the 5-FU group (RR = 0.69, 95%CI 0.52-0.90; P <
      0.00001); the total RR was 0.73 (95%CI 0.64-0.83; P < 0.00001). Our findings
      indicated that HIPC potentially exhibited a lower peritoneal recurrence rate in
      the HIPC group compared to the control group (RR = 0.45, 95%CI 0.28-0.72; P =
      0.001). CONCLUSIONS: Our meta-analysis demonstrated that HIPC may improve the
      overall survival rate for patients who receive resection for advance gastric
      cancer potentially, and help to prevent peritoneal local recurrence among
      patients with serosal invasion in gastric cancer.

PMID- 23153380
TI  - Temporal aggregation impacts on epidemiological simulations employing
      microcontact data.
AB  - BACKGROUND: Microcontact datasets gathered automatically by electronic devices
      have the potential augment the study of the spread of contagious disease by
      providing detailed representations of the study population's contact dynamics.
      However, the impact of data collection experimental design on the subsequent
      simulation studies has not been adequately addressed. In particular, the impact
      of study duration and contact dynamics data aggregation on the ultimate outcome
      of epidemiological models has not been studied in detail, leaving the potential
      for erroneous conclusions to be made based on simulation outcomes. METHODS: We
      employ a previously published data set covering 36 participants for 92 days and a
      previously published agent-based H1N1 infection model to analyze the impact of
      contact dynamics representation on the simulated outcome of H1N1 transmission. We
      compared simulated attack rates resulting from the empirically recorded contact
      dynamics (ground truth), aggregated, typical day, and artificially generated
      synthetic networks. RESULTS: No aggregation or sampling policy tested was able to
      reliably reproduce results from the ground-truth full dynamic network. For the
      population under study, typical day experimental designs - which extrapolate from
      data collected over a brief period - exhibited too high a variance to produce
      consistent results. Aggregated data representations systematically overestimated
      disease burden, and synthetic networks only reproduced the ground truth case when
      fitting errors systemically underestimated the total contact, compensating for
      the systemic overestimation from aggregation. CONCLUSIONS: The
      interdepedendencies of contact dynamics and disease transmission require that
      detailed contact dynamics data be employed to secure high fidelity in simulation
      outcomes of disease burden in at least some populations. This finding serves as
      motivation for larger, longer and more socially diverse contact dynamics tracing
      experiments and as a caution to researchers employing calibrated aggregate
      synthetic representations of contact dynamics in simulation, as the calibration
      may underestimate disease parameters to compensate for the overestimation of
      disease burden imposed by the aggregate contact network representation.

PMID- 23153381
TI  - Synthesis of a potent antimalarial amphilectene.
AB  - 7-Isocyano-11(20),14-epiamphilectadiene, the most potent of antimalarial
      amphilectenes, is synthesized in seven steps from readily available materials.
      The synthesis is enabled by a new dendrimeric triene (Danishefsky [3]-dendralene)
      and a new method for stereo- and chemoselective isocyanation. This chemistry
      provides a useful entry into an underexplored yet promising family of
      antimalarial terpenoids.

PMID- 23153382
TI  - Efficacy of single-session abreactive ego state therapy for combat stress injury,
      PTSD, and ASD.
AB  - Using abreactive Ego State Therapy (EST), 36 patients meeting DSM-IV-TR and PTSD
      checklist (PCL) criteria were exposed to either 5-6 hours of manualized treatment
      or placebo in a single session. EST emphasizes repeated hypnotically activated
      abreactive "reliving" of the trauma experience combined with therapists' ego
      strength. Both the placebo and EST treatment groups showed significant reductions
      in PTSD checklist scores immediately posttreatment (placebo: mean 17.34 points;
      EST: mean 53.11 points) but only the EST patients maintained significant
      treatment effect at 4-week and 16- to 18-week follow-ups. Abreactive EST appears
      to be an effective and durable treatment for PTSD inclusive of combat stress
      injury and acute stress disorder.

PMID- 23153383
TI  - Efficacy of abreactive ego state therapy for PTSD: trauma resolution, depression,
      and anxiety.
AB  - Using manualized abreactive Ego State Therapy (EST), 30 subjects meeting DSM-IV
      TR and Clinician-Administered PTSD Scale (CAPS) criteria were exposed to either 5
      6 hours of treatment or the Ochberg Counting Method (placebo) in a single
      session. EST emphasized repeated hypnotically activated abreactive "reliving" of
      the trauma and ego strengthening by the cotherapists. Posttreatment 1-month and 3
      month follow-ups showed EST to be an effective treatment for PTSD. Using the
      Davidson Trauma Scale, Beck Depression II, and Beck Anxiety Scales, EST subjects
      showed significant positive effects from pretreatment levels at all posttreatment
      measurement periods in contrast to the placebo treatment. Most of the EST
      subjects responded and showed further improvement over time.

PMID- 23153384
TI  - Group hypnotherapy for irritable bowel syndrome with long-term follow-up.
AB  - This study tested whether group gut-focused hypnotherapy would improve irritable
      bowel syndrome (IBS). Several possible outcome predictors were also studied.
      Before treatment, 75 patients completed a Symptom Severity Scale, a Mind-Body
      attribution questionnaire, and a Quality of Relationship Inventory (QRI). The
      symptom scale was completed posttreatment, 3, 6, and 12 months later. There was
      significant symptom reduction at each data point (p < .001). Sixty percent had a
      reduction of more than 50 points, indicative of clinical improvement. Initial
      severity score (p = .0004) and QRI conflict (p = .057) were directly correlated
      with a response to hypnotherapy, while attribution of symptoms to mind
      (emotional) causation was inversely correlated (p = .0056). The authors conclude
      that group hypnotherapy is effective in patients with IBS.

PMID- 23153385
TI  - Flexibility in processing visual information: effects of mood and hypnosis.
AB  - This quasi-experiment using a real/simulator model investigated differences in
      cognitive flexibility in high and low hypnotizable participants. Using the
      variables of hypnotizability (low/high), consciousness
      (nonhypnotized/hypnotized), mood (happy/sad), and visual-information processing
      (global/local), reaction times and target detection paradigms of the subjects
      were evaluated during both nonhypnotic and hypnotic states. Flexibility in
      cognitive processing was operationalized as the ability to overcome the typical
      global precedence and answer quickly about the nonprevalent local features. It
      was observed that the low hypnotizable participants were not influenced in their
      preference for the global or local dimension by any manipulated variable, whereas
      the high hypnotizables were more flexible.

PMID- 23153386
TI  - What motivates professionals to learn and use hypnosis in clinical practice?
AB  - The authors devised and validated a questionnaire assessing the various possible
      motivations for learning and using hypnosis and administered it to 125 Israeli
      psychologists, physicians, and dentists who study and/or use hypnosis in their
      clinical work. The results suggest that most professionals were motivated by a
      desire to improve their professional performance and that a majority of
      professionals were primarily influenced in their desire to learn hypnosis by
      colleagues in academically or clinically oriented settings.

PMID- 23153387
TI  - A cross-validation of two differing measures of hypnotic depth.
AB  - Several sets of regression analyses were completed, attempting to predict 2
      measures of hypnotic depth: the self-reported hypnotic depth score and hypnoidal
      state score from variables of the Phenomenology of Consciousness Inventory:
      Hypnotic Assessment Procedure (PCI-HAP). When attempting to predict self-reported
      hypnotic depth, an R of .78 with Study 1 participants shrank to an r of .72 with
      Study 2 participants, suggesting mild shrinkage for this more attributional
      measure of hypnotic depth. Attempting to predict hypnoidal state (an estimate of
      trance) using the same procedure, yielded an R of .56, that upon cross-validation
      shrank to an r of .48. These and other results suggest that, although there is
      some variance in common, the self-reported hypnotic depth score appears to be
      tapping a different construct from the hypnoidal state score.

PMID- 23153388
TI  - Hypnosis for management of fibromyalgia.
AB  - This randomized, controlled trial contrasted the effects of 5 not-standardized
      sessions of hypnosis over 2 months in 59 women with fibromyalgia who were
      randomly assigned to treatment (n = 30) or a wait-list control group (n = 29).
      Patients in the treated group were encouraged to practice self-hypnosis.
      Fibromyalgia Impact Questionnaire (FIQ), MOS-Sleep Scale, Multidimensional
      Fatigue Inventory (MFI), Cognitive Strategy Questionnaire (CSQ), and Patient
      Global Impression of Change (PGIC) were administered at baseline, 3 months (M3),
      and 6 months (M6) after inclusion. Compared to the control, the hypnosis group
      reported better improvement on PGIC (p = .001 at M3, p = .01 at M6) and a
      significant improvement in sleep and CSQ dramatization subscale (both at M6).

PMID- 23153389
TI  - Imageability, age of acquisition, and frequency factors in acronym comprehension.
AB  - In spite of their unusual orthographic and phonological form, acronyms (e.g.,
      BBC, HIV, NATO) can become familiar to the reader, and their meaning can be
      accessed well enough that they are understood. The factors in semantic access for
      acronym stimuli were assessed using a word association task. Two analyses
      examined the time taken to generate a word association response to acronym cues.
      Responses were recorded more quickly to cues that elicited a large proportion of
      semantic responses, and those that were high in associative strength.
      Participants were shown to be faster to respond to cues which were imageable or
      early acquired. Frequency was not a significant predictor of word association
      responses. Implications for theories of lexical organisation are discussed.

PMID- 23153390
TI  - Sjogren's syndrome-associated oxidative stress and mitochondrial dysfunction:
      prospects for chemoprevention trials.
AB  - An involvement of oxidative stress (OS) was found in recent studies of Sjogren's
      syndrome (SS) that reported significant changes in protein oxidation,
      myeloperoxidase activity, TNF-alpha, nitrotyrosine, and GSH levels in plasma from
      SS patients. Excess levels of OS markers, as oxidative DNA damage and propanoyl
      lysine, were reported in saliva from SS patients. Previous reports concurred with
      a role of OS in SS pathogenesis, by showing a decreased expression of antioxidant
      activities in conjunctival epithelial cells of SS patients and in parotid gland
      tissue samples from SS patients. A link between OS and mitochondrial dysfunction
      (MDF) is recognized both on the grounds of the established role of mitochondria
      in reactive oxygen species (ROS) formation and by the occurrence of MDF in a set
      of OS-related disorders. Earlier studies detected mitochondrial alterations in
      cells from SS patients, related to the action of antimitochondrial
      autoantibodies, and affecting specific mitochondrial activities. Thus, a link
      between MDF and OS may be postulated in SS, prompting studies aimed at
      elucidating SS pathogenesis and in the prospect of chemoprevention trials in SS
      clinical management.

PMID- 23153391
TI  - Cloning and characterization of A cDNA encoding prohibitin1 from Lampetra
      japonica and its expression analysis.
AB  - To investigate that prohibitin is probably concerned in B--lymphocyte--like cells
      mediated signal pathways in Lamprey, a necessary and fundamental plan is firstly
      conducted. A full--length cDNA encoding the prohibitin1 protein was cloned from
      Lampetra japonica by EST sequence analysis in L. japonica leukocyte cDNA library
      conducted by our laboratory. Prohibitin1 contains a 828 bp open reading frame,
      encoded 275 amino acids residues, and molecular weight is 29.9517 KD, isoelectric
      point is 6.93, consists of 31 negatively charged amino acids residues (Asp+Glu)
      and 21 positively charged ones (Arg+Lys). The Prohibitin1 gene sequence from L.
      japonica is 71% identical to the ones of other 24 eukaryotic species, which shows
      the putative prohibitin1 gene is highly conserved. Western blotting analysis
      results showed the recombinant proteins were the target proteins in prokaryote.
      Real--time quantitative polymerase chain reaction analysis indicated that the
      expression of the prohibitin1 gene is significantly up--regulated in leukocyte,
      heart and gill of L. japonica by LPS stress treatment. In conclusion, we have
      cloned and identified the full--length cDNA of Prohibitin1 in L. japonica and
      found that it was related to adaptive immune response in lamprey for the first
      time.

PMID- 23153392
TI  - Migratory gene expression signature predicts poor patient outcome: are cancer
      stem cells to blame?
AB  - Breast cancer metastasis accounts for the majority of deaths from this disease.
      In the previous issue of Breast Cancer Research, Patsialou and colleagues used a
      novel in vivo invasion assay to capture migrating breast cancer cells and
      demonstrate that the gene expression signature of these cells predicts breast
      cancer metastasis in a large cohort of patients. Furthermore, specific genes
      identified play a functional role in the invasion of MDA-MB-231 breast cancer
      cells and in patient-derived breast tumors. These genes regulate pathways known
      to be induced in invasion and metastases and play an important role in the
      regulation of cancer stem cells. 

PMID- 23153393
TI  - High-resolution autosomal radiation hybrid maps of the pig genome and their
      contribution to the genome sequence assembly.
AB  - BACKGROUND: The release of the porcine genome sequence offers great perspectives
      for Pig genetics and genomics, and more generally will contribute to the
      understanding of mammalian genome biology and evolution. The process of producing
      a complete genome sequence of high quality, while facilitated by high-throughput
      sequencing technologies, remains a difficult task. The porcine genome was
      sequenced using a combination of a hierarchical shotgun strategy and data
      generated with whole genome shotgun. In addition to the BAC contig map used for
      the clone-by-clone approach, genomic mapping resources for the pig include two
      radiation hybrid (RH) panels at two different resolutions. These two panels have
      been used extensively for the physical mapping of pig genes and markers prior to
      the availability of the pig genome sequence. RESULTS: In order to contribute to
      the assembly of the pig genome, we genotyped the two radiation hybrid (RH) panels
      with a SNP array (the Illumina porcineSNP60 array) and produced high density
      physical RH maps for each pig autosome. We first present the methods developed to
      obtain high density RH maps with 38,379 SNPs from the SNP array genotyping. We
      then show how they were useful to identify problems in a draft of the pig genome
      assembly, and how the RH maps enabled the problems to be corrected in the porcine
      genome sequence. Finally, we used the RH maps to predict the position of 2,703
      SNPs and 1,328 scaffolds currently unplaced on the porcine genome assembly.
      CONCLUSIONS: A complete process, from genotyping of a high density SNP array on
      RH panels, to the construction of genome-wide high density RH maps, and finally
      their exploitation for validating and improving a genome assembly is presented
      here. The study includes the cross-validation of RH based findings with
      independent information from genetic data and comparative mapping with the Human
      genome. Several additional resources are also provided, in particular the
      predicted genomic location of currently unplaced SNPs and associated scaffolds
      summing up to a total of 72 megabases, that can be useful for the exploitation of
      the pig genome assembly.

PMID- 23153394
TI  - Composition of fatty acids in the maternal and umbilical cord plasma of
      adolescent and adult mothers: relationship with anthropometric parameters of
      newborn.
AB  - BACKGROUND: Considering the importance of long chain polyunsaturated fatty acids
      to fetal development and the lack of studies that have compared the status of
      fatty acids between adolescents and adults mothers, the purpose of this study was
      to evaluate the composition of fatty acids in maternal and umbilical cord plasma
      from adolescent and adults mothers. METHODS: Forty pregnant adolescents and forty
      pregnant adults were selected to assess the distribution profile of fatty acids
      in the maternal and umbilical cord plasma. Quantification of fatty acids in the
      total lipids of the sample groups was performed through the use of gas-liquid
      chromatography. RESULTS: The maternal and umbilical cord plasma of the
      adolescents showed a greater concentration of AA than did that of the adults (P <
      0.05). However, a greater percentage of EPA was found in the umbilical cord
      plasma of the adults (P < 0.05). DHA in the plasma of the adolescent mothers
      correlated positively to birth weight and head circumference. CONCLUSIONS: This
      suggests that in situations of greater nutritional risk, as in adolescent
      pregnancy, n-3PUFA concentrations have a greater influence on the proper
      development of newborns. Moreover, variations in fatty acid concentrations in the
      maternal and cord plasma of adolescents and adults may indicate that pregnancy
      affects the LC-PUFA status of adults and adolescents in distinct ways.

PMID- 23153395
TI  - The Uganda Newborn Study (UNEST): an effectiveness study on improving newborn
      health and survival in rural Uganda through a community-based intervention linked
      to health facilities - study protocol for a cluster randomized controlled trial.
AB  - BACKGROUND: Reducing neonatal-related deaths is one of the major bottlenecks to
      achieving Millennium Development Goal 4. Studies in Asia and South America have
      shown that neonatal mortality can be reduced through community-based
      interventions, but these have not been adapted to scalable intervention packages
      for sub-Saharan Africa where the culture, health system and policy environment is
      different. In Uganda, health outcomes are poor for both mothers and newborn
      babies. Policy opportunities for neonatal health include the new national Health
      Sector Strategic Plan, which now prioritizes newborn health including use of a
      community model through Village Health Teams (VHT). The aim of the present study
      is to adapt, develop and cost an integrated maternal-newborn care package that
      links community and facility care, and to evaluate its effect on maternal and
      neonatal practices in order to inform policy and scale-up in Uganda.
      METHODS/DESIGN: Through formative research around evidence-based practices, and
      dialogue with policy and technical advisers, we constructed a home-based neonatal
      care package implemented by the responsible VHT member, effectively a Community
      Health Worker (CHW). This CHW was trained to identify pregnant women and make
      five home visits - two before and three just after birth - so that linkages will
      be made to facility care and targeted messages for home-care and care-seeking
      delivered. The project is improving care in health units to provide standardized
      care for the mother and the newborn in both intervention and comparison areas.The
      study is taking place in a new Demographic Surveillance Site in two rural
      districts, Iganga and Mayuge, in Uganda. It is a two-arm cluster randomized
      controlled design with 31 intervention and 32 control areas (villages). The
      comparison parishes receive the standard care already being provided by the
      district, but to the intervention villages are added a system for CHWs to visit
      the mother five times in her home during pregnancy and the neonatal period. Both
      areas benefit from a standardized strengthening of facility care for mothers and
      neonates. DISCUSSION: UNEST is designed to directly feed into the
      operationalization of maternal and newborn care in the national VHT strategy,
      thereby helping to inform scale-up in rural Uganda. The study is registered as a
      randomized controlled trial, number ISRCTN50321130.

PMID- 23153396
TI  - Ultraviolet disinfection of antibiotic resistant bacteria and their antibiotic
      resistance genes in water and wastewater.
AB  - Disinfection of wastewater treatment plant effluent may be an important barrier
      for limiting the spread of antibiotic-resistant bacteria (ARBs) and antibiotic
      resistance genes (ARGs). While ideally disinfection should destroy ARGs, to
      prevent horizontal gene transfer to downstream bacteria, little is known about
      the effect of conventional water disinfection technologies on ARGs. This study
      examined the potential of UV disinfection to damage four ARGs, mec(A), van(A),
      tet(A), and amp(C), both in extracellular form and present within a host ARBs:
      methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant
      Enterococcus faecium (VRE), Escherichia coli SMS-3-5, and Pseudomonas aeruginosa
      01, respectively. An extended amplicon-length quantitative polymerase chain
      reaction assay was developed to enhance capture of ARG damage events and also to
      normalize to an equivalent length of target DNA (~1000 bp) for comparison. It was
      found that the two Gram-positive ARBs (MRSA and VRE) were more resistant to UV
      disinfection than the two Gram-negative ARBs (E. coli and P. aeruginosa). The two
      Gram-positive organisms also possessed smaller total genome sizes, which could
      also have reduced their susceptibility to UV because of fewer potential
      pyrimidine dimer targets. An effect of cell type on damage to ARGs was only
      observed in VRE and P. aeruginosa, the latter potentially because of
      extracellular polymeric substances. In general, damage of ARGs required much
      greater UV doses (200-400 mJ/cm2 for 3- to 4-log reduction) than ARB inactivation
      (10-20 mJ/cm2 for 4- to 5-log reduction). The proportion of amplifiable ARGs
      following UV treatment exhibited a strong negative correlation with the number of
      adjacent thymines (Pearson r < -0.9; p < 0.0001). ARBs surviving UV treatment
      were negatively correlated with total genome size (Pearson r < -0.9; p < 0.0001)
      and adjacent cytosines (Pearson r < -0.88; p < 0.0001) but positively correlated
      with adjacent thymines (Pearson r > 0.85; p < 0.0001). This suggests that
      formation of thymine dimers is not the sole mechanism of ARB inactivation.
      Overall, the results indicate that UV is limited in its potential to damage ARGs
      and other disinfection technologies should be explored.

PMID- 23153397
TI  - Terpecurcumins A-I from the rhizomes of Curcuma longa: absolute configuration and
      cytotoxic activity.
AB  - Terpecurcumins A-I (1-9), together with three known analogues (10-12), were
      isolated from the rhizomes of Curcuma longa (turmeric). They were derived from
      the hybridization of curcuminoids and bisabolanes. The structures and absolute
      configurations of 1-9 were elucidated on the basis of extensive spectroscopic
      data analysis, including NMR and electronic circular dichroism spectra. The
      configuration of 10 was further confirmed by X-ray crystallography. A plausible
      biogenetic relationship for 1-12 is proposed. Compounds 4, 6, 7, 10, and 11
      showed higher cytotoxic activities (IC(50), 10.3-19.4 MUM) than curcumin (IC(50),
      31.3-49.2 MUM) against human cancer cell lines (A549, HepG2, and MDA-MB-231).

PMID- 23153398
TI  - Laparoscopic umbilical hernia repair is the preferred approach in obese patients.
AB  - INTRODUCTION: The optimal method of umbilical hernia repair (UHR) in the obese
      population, laparoscopic vs open, is not standardized. The purpose of this study
      was to determine the optimal surgical option for UHR in the obese population.
      METHODS: A retrospective chart review was conducted on 123 obese patients (body
      mass index [BMI] >30) who underwent UHR from 2003 to 2009 at a single
      institution. Patients were grouped by surgical approach (open vs laparoscopic).
      Intraoperative and postoperative courses were compared. Follow-up in the
      postoperative period was obtained from patient records and telephone interviews.
      RESULTS: Of the 123 patients undergoing UHR, 40 and 83 patients were operated on
      with the laparoscopic and open approach, respectively. Patients were well matched
      by demographics as well as comorbidities. No difference in the mean BMI was shown
      between the laparoscopic and open groups (37 vs 35, P = not significant,
      respectively). The operative time was significantly prolonged in the laparoscopic
      group (106 vs 71 minutes, P < .01). Intraoperatively, no complications occurred
      in either group. In the immediate postoperative period, 1 patient who underwent
      laparoscopic UHR was readmitted for small bowel obstruction, and 2 patients in
      the open group were readmitted, 1 for pain control and 1 for wound infection.
      Follow-up was achieved in 63% of the laparoscopic group and 58% of the open group
      with a mean follow-up of 15 months in the laparoscopic group and 20 months in the
      open group (P = not significant). A significant increase in wound infection was
      reported in the open group with mesh insertion when compared with the
      laparoscopic procedure (26% vs 4%, P < .05, respectively). No hernia recurrence
      was shown in the laparoscopic vs the open group with mesh insertion (0% vs 4%, P
      = not significant, respectively). CONCLUSIONS: In obese patients, the
      laparoscopic approach was associated with a significantly lower rate of
      postoperative infection and no hernia recurrence. Laparoscopic hernia repair may
      be the preferred option in the obese patient.

PMID- 23153399
TI  - Total synthesis of (-)-isatisine A.
AB  - A modular total synthesis of (-)-isatisine A is described in which four
      consecutive metal-mediated transformations have been employed at the final stage.
      These include [Pd]-catalyzed Sonogashira coupling, [Pd]-catalyzed nitroalkyne
      cycloisomerization leading to isatogens, and addition of indoles to isatogens
      using InCl(3)- and [Rh]-catalyzed oxidative N-heterocyclization of amino alcohol
      to form the key amide bond. In addition to these, the removal of the protecting
      groups has also been carried out in a selective fashion employing either
      catalytic or stoichiometric metal/metal-based reagents.

PMID- 23153400
TI  - Challenging age-old ideas about stroke.

PMID- 23153401
TI  - Traumatic brain injury and neuropsychiatric outcomes.

PMID- 23153402
TI  - Sham neurosurgical procedures: the patients' perspective.

PMID- 23153403
TI  - West Nile virus bites back.

PMID- 23153404
TI  - Andres Kanner: shining light on the behavioural aspects of epilepsy.

PMID- 23153406
TI  - Antithrombotic therapy for stroke prevention in non-valvular atrial fibrillation.
AB  - The world faces an epidemic of atrial fibrillation and atrial fibrillation
      related stroke. An individual's risk of atrial fibrillation-related stroke can be
      estimated with the CHADS(2) or CHA(2)DS(2)VASc scores, and reduced by two-thirds
      with effective anticoagulation. Vitamin K antagonists, such as warfarin, are
      underused and often poorly managed. The direct thrombin inhibitor dabigatran
      etexilate and factor Xa inhibitors rivaroxaban and apixaban are new oral
      anticoagulants that are at least as efficacious and safe as warfarin. Their
      advantages are predictable anticoagulant effects, low propensity for drug
      interactions, and lower rates of intracranial haemorrhage than with warfarin. A
      disadvantage is the continuing need to develop and validate rapidly effective
      antidotes for major bleeding and standardised tests that accurately measure
      plasma concentrations and anticoagulant effects, together with the disadvantage
      of possible higher rates of gastrointestinal haemorrhage and greater expense than
      with warfarin. The new oral anticoagulants should increase the number of patients
      with atrial fibrillation at risk of stroke who are optimally anticoagulated, and
      reduce the burden of atrial fibrillation-related stroke.

PMID- 23153407
TI  - Measurement and clinical effect of grey matter pathology in multiple sclerosis.
AB  - During the past 10 years, the intense involvement of the grey matter of the CNS
      in the pathology of multiple sclerosis has become evident. On gross inspection,
      demyelination in the grey matter is rather inconspicuous, and lesions in the grey
      matter are mostly undetectable with traditional MRI sequences. However, the
      results of immunohistochemical studies have shown extensive involvement of grey
      matter, and researchers have developed and applied new MRI acquisition methods as
      a result. Imaging techniques specifically developed to visualise grey matter
      lesions indicate early involvement, and image analysis techniques designed to
      measure the volume of grey matter show progressive loss. Together, these
      techniques have shown that grey matter pathology is associated with neurological
      and neuropsychological disability, and the strength of this association exceeds
      that related to white matter lesions or whole brain atrophy. By focusing on the
      latest insights into the in-vivo measurement of grey matter lesions and atrophy,
      we can assess their clinical effects.

PMID- 23153408
TI  - Cognitive decline in older adults with a history of traumatic brain injury.
AB  - Traumatic brain injury (TBI) is an important public health problem with
      potentially serious long-term neurobehavioural sequelae. There is evidence to
      suggest that a history of TBI can increase a person's risk of developing
      Alzheimer's disease. However, individuals with dementia do not usually have a
      history of TBI, and survivors of TBI do not invariably acquire dementia later in
      life. Instead, a history of traumatic brain injury, combined with brain changes
      associated with normal ageing, might lead to exacerbated cognitive decline in
      older adults. Strategies to increase or maintain cognitive reserve might help to
      prevent exacerbated decline after TBI. Systematic clinical assessment could help
      to differentiate between exacerbated cognitive decline and mild cognitive
      impairment, a precursor of Alzheimer's disease, with important implications for
      patients and their families.

PMID- 23153409
TI  - Autonomous movement of controllable assembled Janus capsule motors.
AB  - We demonstrate the first example of a self-propelled Janus polyelectrolyte
      multilayer hollow capsule that can serve as both autonomous motor and smart
      cargo. This new autonomous Janus capsule motor composed of partially coated
      dendritic platinum nanoparticles (Pt NPs) was fabricated by using a template
      assisted layer-by-layer (LbL) self-assembly combined with a microcontact printing
      method. The resulting Janus capsule motors still retain outstanding delivery
      capacities and can respond to external stimuli for controllable encapsulation and
      triggered release of model drugs. The Pt NPs on the one side of the Janus capsule
      motors catalytically decompose hydrogen peroxide fuel, generating oxygen bubbles
      which then recoil the movement of the capsule motors in solution or at an
      interface. They could autonomously move at a maximum speed of above 1 mm/s (over
      125 body lengths/s), while exerting large forces exceeding 75 pN. Also, these
      asymmetric hollow capsules can be controlled by an external magnetic field to
      achieve directed movement. This LbL-assembled Janus capsule motor system has
      potential in making smart self-propelling delivery systems.

PMID- 23153410
TI  - Clinical impact of unsolicited post-prescription antibiotic review in surgical
      and medical wards: a randomized controlled trial.
AB  - This study aimed to determine the clinical course of patients and the quality of
      antibiotic use using a systematic and unsolicited post-prescription antibiotic
      review. Seven hundred and fifty-three adult patients receiving antibiotic therapy
      for 3-5 days were randomized to receive either a post-prescription review by the
      infectious disease physician (IDP), followed by a recommendation to the attending
      physician to modify the prescription when appropriate, or no systematic review of
      the prescription. In the intervention group, 63.3% of prescriptions prompted IDP
      recommendations, which were mostly followed by ward physicians (90.3%). Early
      antibiotic modifications were more frequent in the intervention group (57.1% vs.
      25.7%, p <0.0001), including stopping therapy, shortening duration and de
      escalating broad-spectrum antibiotics. IDP intervention led to a significant
      reduction of the median [IQR] duration of antibiotic therapy (6 [4-9] vs. 7 days
      [5-9], p <0.0001). In-hospital mortality, ICU admission and new course of
      antibiotic therapy rates did not differ between the two groups. Fewer patients in
      the intervention group were readmitted for relapsing infection (3.4% vs. 7.9%, p
      0.01). There was a trend for a shorter length of hospital stay in patients
      suffering from community-acquired infections in the intervention group (5 days [3
      10] vs. 6 days [3-14], p 0.06). This study provides clinical evidence that a post
      prescription antibiotic review followed by unsolicited IDP advice is effective in
      reducing antibiotic exposure of patients and increasing the quality of antibiotic
      use, and may reduce hospital stay and relapsing infection rates, with no adverse
      effects on other patient outcomes.

PMID- 23153411
TI  - Aggregation and dynamics of oligocholate transporters in phospholipid bilayers
      revealed by solid-state NMR spectroscopy.
AB  - Macrocycles made of cholate building blocks were previously found to transport
      glucose readily across lipid bilayers. In this study, an (15)N, (13)Calpha
      labeled glycine was inserted into a cyclic cholate trimer and attached at the end
      of a linear trimer, respectively. The isotopic labeling allowed us to use solid
      state NMR spectroscopy to study the dynamics, aggregation, and depth of insertion
      of these compounds in lipid membranes. The cyclic compound was found to be mostly
      immobilized in DLPC, POPC/POPG, and POPC/POPG/cholesterol membranes, whereas the
      linear trimer displayed large-amplitude motion that depended on the membrane
      thickness and viscosity. (13)C-detected (1)H spin diffusion experiments revealed
      the depth of insertion of the compounds in the membranes, as well as their
      contact with water molecules. The data support a consistent stacking model for
      the cholate macrocycles in lipid membranes, driven by the hydrophobic
      interactions of the water molecules in the interior of the macrocycles. The study
      also shows a strong preference of the linear trimer for the membrane surface,
      consistent with its lack of transport activity in earlier liposome leakage
      assays.

PMID- 23153412
TI  - Reactive transport modeling of chromium isotope fractionation during Cr(VI)
      reduction.
AB  - Chromium isotope fractionation is indicative of mass-transfer processes, such as
      reduction of Cr(VI) to Cr(III) during groundwater remediation. Laboratory
      experiments comparing batch and column treatment of Cr(VI) using organic carbon
      suggest that the associated isotope fractionation may be influenced by solute
      transport mechanisms. These batch and column experiments were simulated using the
      reactive transport model MIN3P to further evaluate the effects of Cr reduction
      and transport on isotope fractionation under saturated flow conditions.
      Simulation of the batch experiment provided a good fit to the experimental data,
      where a fractionation factor (alpha53) of 0.9965 was attributed to a single,
      dominant Cr(VI) removal mechanism. Calibration of the column simulations to the
      experimental results suggested the presence of a second, more rapid Cr(VI)
      removal mechanism with alpha53 = 0.9992. Results from this study demonstrate that
      the interpretation of Cr isotope fractionation during reduction can be complex,
      particularly where multiple removal mechanisms are evident. Reactive transport
      modeling of Cr isotope fractionation can provide a quantitative assessment of the
      contaminant removal mechanisms, thus improving the application of Cr isotope
      measurements as a tool to track Cr(VI) migration and attenuation in groundwater.

PMID- 23153413
TI  - [The Mexican consensus on gastroesophageal reflux disease. Part I].
AB  - BACKGROUND: The changes, advances, and new discoveries regarding different
      aspects of gastroesophageal reflux disease (GERD) have made it necessary to
      update the Mexican Consensus published in 2002. AIMS: To elaborate a new Mexican
      Consensus on GERD. METHODS: The general project coordinators selected six GERD
      experts to carry out an extensive review of the literature for the purpose of
      elaborating statements on the principal aspects of GERD. These were then placed
      under the consideration of specialists in the study of this disease. Definitive
      approval by all participants was reached using the modified Delphi method with
      three rounds of anonymous and iterative voting. The following scale was employed:
      A- in complete agreement; B- in agreement, but with minor concerns; C- in
      agreement, but with major concerns; D- in disagreement, but with major concerns;
      E- in disagreement, but with minor concerns; or F- in complete disagreement.
      Consensus was declared when 67.00% or more of the participants concurred on a
      category of agreement (A, B, or C). RESULTS: A consensus was reached on 160 of
      the statements upon completion of the voting rounds, with 90.00% concurrence for
      the majority of them. CONCLUSIONS: The 2011 Mexican Consensus on Gastroesophageal
      Disease is a practical and up-to-date consultation tool, providing the opinion of
      Mexican experts on all the new information available about this disease. It
      allows there to be homogeneity in diagnostic and therapeutic criteria, all of
      which serves to benefit our patients.

PMID- 23153414
TI  - [Clostridium difficile: Is it time to start worrying?].

PMID- 23153415
TI  - [The "rendez-vous" maneuver as a technical option to access the bile ducts: case
      series report].
AB  - The "rendez-vous" maneuver is a technical option, to have in mind, for the bile
      ducts access. This technique assures a "guided" canulation of the bile duct
      during the laparoscopic cholecystectomy (LC). We analyzed three clinical cases of
      patients with cholecysto-choledocolithiasis, in whose were planned Endoscopic
      Retrograde Cholangio-Pancreatography (ERCP) and LC during the same surgical
      intervention. The "rendez-vous" maneuver was employed as a technical option to
      access the bile duct, after an initial (failed) endoscopic attempt of
      cannulation. An intraoperative cholangiography was performed and a guide wire was
      inserted through the cystic duct, allowing the endoscopic capture and the guided
      cannulation of the bile duct. The therapeutic objective was achieved in all
      patients. There was not associated morbid-mortality and all patients were
      satisfied with the surgical outcome. In these series of cases, the "rendez-vous"
      maneuver was a viable, safe and useful technical option to access the bile ducts.
      Futhermore, the cholecysto-choledocolithiasis was treated during the same
      surgical intervention. A postoperative bile duct exploration becomes unnecessary.

PMID- 23153416
TI  - [Blue rubber bleb nevus syndrome: A case report].
AB  - Blue Rubber Bleb Nevus Syndrome (BRBS) is a rare disease, characterized by
      multiple vascular malformations in the skin and gastrointestinal tract. Other
      organs can also be affected, presenting different clinical manifestations such as
      arthralgia, epistaxis, hemoptysis, hematuria, hemothorax, mild thrombocytopenia,
      consumptive coagulopathy, and bone deformities, among others. We present a case
      of BRBS in a nine-year-old boy with the characteristic clinical manifestations of
      punctated purplish-blue skin lesions that vary in size and gastrointestinal
      vascular malformations with upper digestive tract bleeding.

PMID- 23153417
TI  - An ECM-based culture system for the generation and maintenance of xeno-free human
      iPS cells.
AB  - Pluripotent stem cells (PSCs) including induced pluripotent stem cells (iPSCs)
      and embryonic stem cells (ESCs) have emerged as a promising source for treating
      incurable diseases. Problems that urgently need to be resolved before the
      clinical application include avoiding potential xenopathogenic transmission and
      immune rejection that may be caused by the exposure of PSCs to animal-derived
      products. In addition, an efficient feeder cell-free culture condition would be
      required for reducing batch-to-batch variation and facilitating scale-up.
      Therefore, establishing an efficient xeno-free and extracelluar matrix-based
      culture system is a prerequisite for the clinical application of PSCs. In this
      study, by blocking protein kinase C and histone deacetylase activities, we
      formulated a medium that, in combination with vitronectin as an extracellular
      matrix, not only allows the long-term culture of hESCs and iPSCs but also
      efficiently generates xeno-free iPSCs. This xeno-free and feeder cell-free
      culture system would facilitate the clinical applications of both iPSC- and ESC
      based cell therapies in the future.

PMID- 23153418
TI  - The effect of graphene oxide on conformation change, aggregation and cytotoxicity
      of HIV-1 regulatory protein (Vpr).
AB  - The fragment of viral protein R (Vpr), Vpr13-33, plays an important role in
      regulating nuclear importing of HIV through ion channel formation with a leucine
      zipper-like alpha-helical conformation. Herein we report an approach to reduce
      cytotoxicity of Vpr13-33 by graphene oxide induced conformation change and
      aggregation. Preferential adsorption of Vpr13-33 on graphene oxide accompanied by
      conformation change from alpha-helix to beta-sheet structures has been observed
      by using atomic force microscopy (AFM) and circular dichroism (CD). The
      submolecular structures of the Vpr13-33 peptide assembly on graphite surface have
      been identified by using scanning tunneling microscopy (STM), which confirms the
      beta-sheet structures of Vpr13-33 on graphene oxide surface. The reduced
      cytotoxicity of Vpr13-33 to neuroblastoma cells and T cells are detected by MTT
      assay, which could be associated with the conformation change and stimulated
      aggregation of Vpr13-33 upon addition of graphene oxide through hydrophobic
      interaction. Furthermore, fluorescent leakage assay by using large unilamellar
      vesicles (LUVs) indicated that the GO reduced Vpr13-33-induced cytotoxicity could
      be associated with the inhibited "pore forming" function of Vpr13-33 by
      conformation change and aggregation.

PMID- 23153420
TI  - Fibroblast growth factor 2 induces the precocious development of endothelial cell
      networks in bovine luteinising follicular cells.
AB  - The transition from follicle to corpus luteum represents a period of intense
      angiogenesis; however, the exact roles of angiogenic factors during this time
      remain to be elucidated. Thus, the roles of vascular endothelial growth factor
      (VEGF) A, fibroblast growth factor (FGF) 2 and LH in controlling angiogenesis
      were examined in the present study. A novel serum-free luteinising follicular
      angiogenesis culture system was developed in which progesterone production
      increased during the first 5 days and was increased by LH (P<0.01). Blockade of
      signalling from FGF receptors (SU5402; P<0.001) and, to a lesser extent, VEGF
      receptors (SU1498; P<0.001) decreased the development of endothelial cell (EC)
      networks. Conversely, FGF2 dose-dependently (P<0.001) induced the precocious
      transition of undeveloped EC islands into branched networks associated with a
      twofold increase in the number of branch points (P<0.001). In contrast, VEGFA had
      no effect on the area of EC networks or the number of branch points. LH had no
      effect on the area of EC networks, but it marginally increased the number of
      branch points (P<0.05) and FGF2 production (P<0.001). Surprisingly, progesterone
      production was decreased by FGF2 (P<0.01) but only on Day 5 of culture.
      Progesterone production was increased by SU5402 (P<0.001) and decreased by SU1498
      (P<0.001). These results demonstrate that FGF and VEGF receptors play a
      fundamental role in the formation of luteal EC networks in vitro, which includes
      a novel role for FGF2 in induction of EC sprouting.

PMID- 23153419
TI  - Inflammation and diabetes-accelerated atherosclerosis: myeloid cell mediators.
AB  - Monocytes and macrophages respond to and govern inflammation by producing a
      plethora of inflammatory modulators, including cytokines, chemokines, and
      arachidonic acid (C20:4)-derived lipid mediators. One of the most prevalent
      inflammatory diseases is cardiovascular disease, caused by atherosclerosis, and
      accelerated by diabetes. Recent research has demonstrated that
      monocytes/macrophages from diabetic mice and humans with type 1 diabetes show
      upregulation of the enzyme, acyl-CoA synthetase 1 (ACSL1), which promotes C20:4
      metabolism, and that ACSL1 inhibition selectively protects these cells from the
      inflammatory and proatherosclerotic effects of diabetes, in mice. Increased
      understanding of the role of ACSL1 and other culprits in monocytes/macrophages in
      inflammation and diabetes-accelerated atherosclerosis offers hope for new
      treatment strategies to combat diabetic vascular disease.

PMID- 23153421
TI  - Early discharge does not increase readmission or mortality after high-risk
      vascular surgery.
AB  - PURPOSE: Clinical pathways aimed at reducing hospital length of stay following
      vascular surgery have been broadly implemented to reduce costs. However, early
      hospital discharge may adversely affect the risk of readmission or mortality. To
      address this question, we examined the relationship between early discharge and
      30-day outcomes among patients undergoing a high-risk vascular surgery procedure,
      thoracic aortic aneurysm (TAA) repair. METHODS: Using Medicare claims from 2000
      to 2007, we identified all patients who were discharged home following elective
      thoracic endovascular aneurysm repair (TEVAR) and open repair for nonruptured
      TAAs. For each procedure, we examined the correlation between early discharge (<3
      days for TEVAR, <7 days for open TAA repair) and 30-day readmission, 30-day
      mortality, and hospital costs. Predictors of readmission were evaluated using
      logistic regression models controlling for patient comorbidities, perioperative
      complications, and discharge location. RESULTS: Our sample included 9764
      patients, of which 7850 (80%) underwent open TAA repair, and 1914 (20%) underwent
      TEVAR. Patients discharged to home early were more likely to be female (66% early
      vs 56% late), Caucasian (94% early vs 91% late), younger (73 years early vs 74
      years late), and have fewer comorbidities (mean Charlson score: 0.7 early vs 1.0
      late) than patients discharged home late (all P < .01). As compared with patients
      who were discharged late, patients discharged home early following uncomplicated
      open TAA repair and TEVAR had significantly lower 30-day readmission rates
      ([open: 17% vs 24%; P < .001] [TEVAR: 12% vs 23%; P < .001]) and hospital costs
      ([open: $73,061 vs $136,480; P < .001] [TEVAR: $58,667 vs $128,478; P < .001]),
      without an observed increase in 30-day postdischarge mortality. In multivariable
      analysis, early hospital discharge was associated with a significantly lower
      likelihood of readmission following both open TAA repair (odds ratio, 0.70; 95%
      confidence interval, 0.57-0.85; P < .001) and TEVAR (odds ratio, 0.57; 95%
      confidence interval, 0.38-0.85; P < .01) procedures. CONCLUSIONS: Discharging
      patients home early following uncomplicated TEVAR or open TAA repair is
      associated with reduced hospital costs without adversely impacting 30-day
      readmission or mortality rates. These data support the safety and cost
      effectiveness of programs aimed at early hospital discharge in selected vascular
      surgery patients.

PMID- 23153422
TI  - Current status and future developments of contrast-enhanced ultrasound of carotid
      atherosclerosis.
AB  - B-mode and Doppler ultrasound are commonly used for the evaluation of
      atherosclerosis in the carotid arteries. Recently, contrast-enhanced ultrasound
      (CEUS) has been introduced as a technique to improve the detection of carotid
      atherosclerosis and evaluate the presence of intraplaque neovascularization,
      which is considered a marker of plaque vulnerability. The present review focuses
      on the role of CEUS for the assessment of atherosclerosis and plaque instability.
      Currently available literature and future developments with CEUS are discussed.

PMID- 23153423
TI  - Primary balloon angioplasty of small (<=2 mm) cephalic veins improves primary
      patency of arteriovenous fistulae and decreases reintervention rates.
AB  - PURPOSE: The purpose of this study was to evaluate the effect of primary balloon
      angioplasty (PBA) of cephalic veins with diameter<=2 mm on patency and maturation
      time of autogenous radiocephalic arteriovenous fistulae (AVF) for hemodialysis.
      METHODS: Forty patients, all candidates for distal AVF, with a cephalic vein<=2
      mm, were randomized to two different surgical procedures: (1) PBA of a long
      segment of the cephalic vein from the wrist up to the elbow (n=19); and (2)
      hydrostatic dilatation (HD) of a short venous segment (5 cm) at the level of the
      anastomosis (n=21). PBA was performed using a standard balloon 4*150 mm. Primary
      end points were primary patency and reintervention rates. Secondary end points
      were maturation time and the rate of working AVF. Follow-up included physical and
      duplex ultrasound (DUS) examinations at 1,4, and 8 weeks, and every 3 months
      thereafter. RESULTS: Risk factors were homogeneously distributed between the two
      groups. Mean vein diameter was 1.8+/-0.2 mm for the PBA group and 1.7+/-0.2 mm
      for HD. Immediate success rate was 100% for PBA and 67% for HD groups (P=.04).
      Causes of failure in the HD group included early vein thrombosis in seven
      patients (33%). Mean fistula maturation time was 32 days in the PBA group and 55
      days in the HD group (P=.04). During the mean follow-up of 7 months, three
      patients underwent drug-eluting balloon angioplasty for failure of AVF to mature
      due to stenosis (1 in the PBA group and 2 in the HD group). Six-month
      reintervention rate was significantly lower in the PBA group (5%) compared with
      the HD group (43%) (P=.02). At 6 months, primary patency rates were 95% in the
      PBA group and 57% in the HD group (P=.01). Working AVF rate was 100% in the PBA
      vs 90% in the HD group. CONCLUSIONS: PBA of very small cephalic veins during the
      creation of a distal AVF for hemodialysis is a safe and feasible procedure. This
      technique assures excellent primary patency, maturation time, and dramatically
      decreases reintervention rate.

PMID- 23153424
TI  - [Surgical treatment of liver metastases of gastric cancer].
AB  - INTRODUCTION: Gastric cancer, despite of its decreasing incidence, remains a
      serious medical problem. Many patients see a specialist as late as in the IVth
      stage of the disease with peritoneal seedings or liver metastases. Liver
      resection for gastric cancer metastases remains to be a controversial issue.
      MATERIAL AND METHODS: The aim of this study is to present, through our case
      report and literature review, the current opinions on liver resections for
      metastatic gastric cancer. RESULTS: Based on our experience and review of the
      Medline literature of the last five years, we would like to present the current
      trends in this field. CONCLUSIONS: Liver resection for gastric cancer metastases
      remains a controversial topic. However, in a very carefully selected group of
      patients, improved survival can be reached by combining liver resection and
      modern systemic treatment.

PMID- 23153425
TI  - [Delayed gastric emptying after partial duodenopancreatectomy].
AB  - INTRODUCTION: Delayed gastric emptying (DGE) is a relatively common complication
      in patients after partial duodenopancreatectomy (PDPE) and significantly
      contributes to their postoperative morbidity. There has only been a small amount
      of interest attributed to DGE in Czech literature. The aim of this article is to
      present and analyze our own experience with the occurrence of DGE after PDPE.
      MATERIALS AND METHODS: Retrospective analysis of prospectively collected data
      from 106 patients who underwent a PDPE at the Department of Surgery, University
      Hospital Motol and 2nd Medical Faculty, between 2001 and 2011. The data were
      statistically analyzed using the Chi-square test with statistical significance
      set at 5% of probability value (p < 0.05). RESULTS: During the reporting period,
      PDPE was performed in 106 patients with a pathological process in the pancreatic
      head. 4 patients died in the postoperative period (30-day mortality 3.8%). Major
      postoperative complications occurred in 31 patients (morbidity 29%), with
      clinically significant DGE (grade B and C) in almost half of them (16 patients).
      Along with the DGE, 4 patients suffered from other major complications (2
      pancreatic anastomotic insufficiency, 1 bile fistula and 1 external pancreatic
      fistula). We did not prove a statistically significant difference in the
      incidence of DGE depending either on the type of resection or pancreatic
      anastomosis type. CONCLUSION: DGE contributes significantly to postoperative
      morbidity in patients after PDPE and is associated with other serious
      postoperative complications in a considerable number of cases.

PMID- 23153426
TI  - [K-ras mutational status and tumour-infiltrating lymphocytes in human colon
      cancer: state of the art and future perspectives].
AB  - INTRODUCTION: Nowadays, the prognosis of newly diagnosed colorectal cancer
      patients relies mostly on the tumour-node-metastasis (TNM) classification which
      is also a determining criterion for the indication of adjuvant oncological
      treatment. Currently, new prognostic and predictive biomarkers are sought after
      in order to more precisely define prognosis and better predict the benefits of
      adjuvant treatment in colorectal cancer. Besides several molecular biomarkers,
      such as mutations in the proto-oncogene K-ras, analyses of tumour-infiltrating
      lymphocytes have shown promising prognostic value. The aim of the study is to
      examine the correlations between K-ras mutational status and tumour-infiltrating
      immune cells in colon cancer patients with respect to colon cancer recurrence.
      MATERIAL AND METHODS: Formalin-fixed paraffin-embedded specimens were obtained
      from 44 patients with surgically resected colon cancer (R0 resection) treated
      between 2004 and 2009. K-ras mutational status was detected using PCR
      amplification of exon 1 followed by direct sequencing and K-ras StripAssay.
      Tumour-infiltrating immune cells were detected by immunofluorescence staining
      using monoclonal antibodies against CD3, CD8, FoxP3, CD1a and DC-LAMP. RESULTS:
      All 44 patients in our cohort underwent radical resection of colon cancer. In 16
      patients the tumour relapsed (36.4%). K-ras mutations were found in 45.5% (n=20)
      of the primary carcinomas: 65% in codon 12 and 35% in codon 13. Although codon 13
      K-ras mutations were associated with disease relapse, they were present in both
      disease-free and relapsed patients. However, disease-free and relapsed patients
      differed markedly in their patterns of tumour-infiltrating immune cells. There
      was a trend towards decreased density of tumour-infiltrating lymphocytes within
      the group of relapsed patients. In addition, relapsed patients with codon 13
      mutations had markedly lower levels of tumour-infiltrating mature DC-LAMP+
      dendritic cells and higher frequency of CD1a+ cells compared to disease-free
      patients. CONCLUSION: Colon cancer patients with low levels of tumour
      infiltrating lymphocytes, a high CD1a+/DC-LAMP+ tumour-infiltrating DC ratio and
      a K-ras mutation in codon 13 are at a high risk of disease recurrence.

PMID- 23153427
TI  - [Injury to the abdominal wall by a foreign body with  a late perforation of the
      GIT].
AB  - The authors present the case of a patient with an abdominal puncture wound who
      developed, in two weeks, perforation of the colon with an unrecognized foreign
      body in the abdominal cavity.

PMID- 23153428
TI  - [Complications of breast augmentation  - a case report].
AB  - As with any surgery, breast augmentation does have certain risks and
      complications. The aim of this article is to point out a rare complication of
      breast augmentation - axillary silicone lymphadenopathy (defined as the presence
      of silicone in the lymph nodes). The authors present a case report of silicone
      lymphadenopathy in a young woman after the rupture of a silicone breast implant.
      As the number of women with breast implants is increasing, it is necessary to
      bear this rare complication of breast augmentation in mind in differential
      diagnosis of axillary lymphadenopathy.

PMID- 23153430
TI  - [Endoscopic therapy of early gastric carcinoma].

PMID- 23153431
TI  - [Surgical treatment of gastric carcinoma].

PMID- 23153432
TI  - [Surgical treatment of gastroesophageal junction tumors].

PMID- 23153433
TI  - [Laparoscopic surgery for gastric carcinoma].

PMID- 23153434
TI  - [Use of laser Doppler to assess peripheral tissue perfusion in critically ill
      children].
AB  - OBJECTIVE: To analyze skin tissue perfusion at different sites in critically ill
      children. PATIENTS AND METHODS: A prospective observational study was performed
      on 41 critically ill children with a median age of 12 months and weight of 8.2
      kg. Skin tissue flow was measured in each patient using laser Doppler
      consecutively in the foot, forearm, thigh and hypochondrium, and its association
      with demographic and hemodynamic variables, as well as lactate and inotropic
      index, was analyzed. RESULTS: A total of 144 tissue flow measurements were made,
      with a median flow of 3.2+/-2.2 ml/min/100 g tissue. There was a moderate
      correlation between the tissue flow measured in central locations, abdomen-arm
      (r(2): 0.574, P=.001), abdomen-thigh (r(2): 0.423, P=.002) and thigh-arm (r(2):
      0.703, P<.000), but not with the peripheral measurements (sole of the foot). The
      limits of agreement, measured between the different locations, were wide (range
      6.1 to -2.5 ml/min/100g). There was a slight-moderate correlation between the
      flow in the sole of the foot with weight (-0.355, P=.039), age (-0.343, P=.044),
      peripheral temperature (0.503, P=.017) and inotropic index (-0.443, P=.008).
      CONCLUSIONS: Tissue flow in the foot correlates with weight, age, peripheral
      temperature and inotropic index. Further studies are needed to analyze its
      usefulness in assessing peripheral perfusion in situations of shock.

PMID- 23153435
TI  - Fasting blood glucose and insulin sensitivity are unaffected by HAART duration in
      Cameroonians receiving first-line antiretroviral treatment.
AB  - AIMS: This study assessed the relationship between highly active antiretroviral
      therapy (HAART) duration and cardiometabolic disorders in HIV-infected
      Cameroonians. METHODS: HIV-infected Cameroonians aged 21 years or above were
      cross-sectionally recruited at the Yaounde Central Hospital, a certified HIV care
      centre, and their anthropometry, body composition (impedancemetry), fasting blood
      glucose (FBG) and lipid levels, and insulin sensitivity (IS; short insulin
      tolerance test) were measured. RESULTS: A total of 143 participants with various
      durations of HAART [treatment-naive (n=28), 1-13 months (n=44), 14-33 months
      (n=35) and 34-86 months (n=36)] were recruited. They were mostly women (72%), and
      had a mean age of 39.5 (SD: 9.8) years. Half (52%) were using a stavudine
      containing regimen. There was a significant trend towards a positive change in
      body mass index and waist-to-hip ratio with increasing duration of HAART (all
      P=0.02). Systolic (P=0.04) and diastolic (P=0.03) blood pressure, total
      cholesterol (P=0.01), prevalence of hypertension (P=0.04) and
      hypercholesterolaemia (P=0.007) were also significantly increased with HAART
      duration, whereas triglycerides, FBG and IS were unaffected. Clustering of
      metabolic disorders increased (P=0.02 for >=1 component of the metabolic syndrome
      and P=0.09 for >=2 components) with HAART duration. CONCLUSION: HAART duration is
      associated with obesity, fat distribution, blood pressure and cholesterol levels
      in HIV-infected Cameroonians, but does not appear to significantly affect glucose
      metabolism.

PMID- 23153436
TI  - Lgr5 is a potential marker of colorectal carcinoma stem cells that correlates
      with patient survival.
AB  - BACKGROUND: Lgr5 (leucine-rich-repeat-containing G-protein-coupled receptor 5)
      has recently been identified as an intestinal stem cell marker. In order to
      determine whether Lgr5 is a potential marker of cancer stem cells, we
      investigated whether Lgr5 expression correlated with Ki-67 expression and
      prognosis in colorectal carcinoma. METHODS: Lgr5 and Ki-67 expression were
      evaluated by immunohistochemistry in 192 colorectal carcinoma specimens.
      Selection of side population (SP) cells was performed by staining with Hoechest
      33342, and Lgr5 expression in Colo205 SP cells was then detected by
      immunofluorescence. RESULTS: Lgr5 expression was significantly higher in
      carcinoma than in normal mucosa (P=0.001). Lgr5 was positively correlated with
      histological grade (P=0.001), depth of invasion (P=0.001), lymph node metastasis
      (P=0.001), distant metastasis (P=0.004), pTNM stage (P=0.001), and Ki-67
      (r=0.446, P=0.001). Multivariate analysis showed that the effect of Lgr5 on
      survival was independent of Ki-67 (P=0.037). In the in vitro study, Hoechst low
      staining cells were counted in 7% of the Colo205 colon cancer cell line
      population, and Lgr5 expression was strikingly stronger in Hoechst low-staining
      cells than in high-staining cells (P=0.001). CONCLUSIONS: These findings suggest
      that Lgr5 may play an important role in the progression and prognosis of
      colorectal carcinoma, and may be a potential new therapeutic target for the
      treatment of colorectal cancer patients. It may also be considered as a potential
      marker for colorectal cancer stem cells (CSCs).

PMID- 23153437
TI  - Safety and immunogenicity of the pneumococcal pneumolysin derivative PlyD1 in a
      single-antigen protein vaccine candidate in adults.
AB  - BACKGROUND: Pneumococcal vaccines based on conserved protein antigens have the
      potential to offer expanded protection against Streptococcus pneumoniae.
      OBJECTIVE: This study examined the safety and immunogenicity in adults of three
      doses of a pneumococcal single-antigen protein vaccine candidate formulated with
      aluminum hydroxide adjuvant and recombinantly derived, highly detoxified,
      genetically mutated pneumolysin protein (PlyD1). METHODS: This phase I,
      randomized, placebo-controlled, observer-blinded, dose-escalating study enrolled
      adults (18-50 years). In a pilot safety study, participants received a single
      injection of 10 MUg PlyD1 and were observed for 24 h. Following review of the
      pilot safety data, participants were randomized (2:1) to receive two injections
      of PlyD1 at one of three doses or placebo 30 days apart. Assignment of second
      injection and successive dose cohorts was made after blinded safety reviews after
      each injection at each dose level. Safety endpoints included rates of solicited
      injection site reactions, solicited systemic reactions, unsolicited adverse
      events (AEs), serious AEs (SAEs), and safety laboratory tests. Immunogenicity
      endpoints included geometric mean concentrations of anti-PlyD1 IgG as determined
      by ELISA and functional assessment in an in vitro toxin neutralization assay.
      RESULTS: The study included a total of 100 participants, including 10 in the
      pilot study and 90 in the randomized study. None of the participants in the pilot
      study had SAEs, allergic reactions, or other safety concerns. Ninety participants
      received two doses of or placebo (n=30) or active vaccine candidate at 10 (n=20),
      25 (n=20), or 50 MUg (n=20). No vaccine-related SAE or discontinuation due to an
      AE occurred. Most solicited reactions were mild and transient. The most
      frequently reported solicited reactions were pain at the injection site and
      myalgia. Antigen-specific IgG levels and functional activity showed dose-related
      increases. When comparing the three dose levels, a plateau effect was observed at
      the 25 MUg dose. CONCLUSIONS: All dose levels were safe and immunogenic. Repeat
      vaccination significantly increased the level of anti-PlyD1 antibodies.
      Functional antibody activity was demonstrated in sera from vaccinated individuals
      (ClinicalTrials.gov no. NCT01444352).

PMID- 23153438
TI  - Yersinia enterocolitica ghost with msbB mutation provides protection and reduces
      proinflammatory cytokines in mice.
AB  - Yersinia enterocolitica is an important human pathogen. Yersiniosis, caused by Y.
      enterocolitica, has become more prevalent globally in recent years. Prevention of
      yersiniosis still remains a challenge, and an efficacious and safe vaccine that
      confers protection against this enteric pathogen needs to be developed. In this
      study, a novel vaccine based on the bacterial ghost, in combination with mutation
      of the Y. enterocolitica msbB gene, was developed and the immunopotency of this
      vaccine was evaluated in mice. Significant levels of IgG1/IgG2a antibodies and IL
      4/IFN-gamma cytokines were detected after mice were administered this vaccine
      intragastrically, indicating that a Th1/Th2-mediated mixed immune response was
      stimulated. Importantly, mutation of the msbB gene efficiently reduced secretion
      of the proinflammatory cytokines IL-1beta, IL-6 and TNF-alpha, suggesting a
      reduction in inflammatory reaction caused by lipopolysaccharide. In addition,
      when challenged with a dose that was 100-fold the minimal lethal dose of the
      virulent wild strain of Y. enterocolitica, this mutated ghost vaccine was capable
      of eliciting the same effective protection (80%) in comparison with the non
      mutated ghost strain, and the survival time was extended by at least two days.
      Together, our results demonstrated that this novel ghost bacterial strain could
      be used as a safe and effective vaccine against Y. enterocolitica.

PMID- 23153439
TI  - Cost-effectiveness of adult pneumococcal vaccination: responding to: Weycker D,
      Sato R, Strutton D, Edelsberg J, Atwood M, Jackson LA. Public health and economic
      impact of 13-valent pneumococcal conjugate vaccine in US adults aged >=50 years.
      Vaccine 2012;30(August (36)):5437-44.

PMID- 23153440
TI  - Low opsonic activity to the infecting serotype in pediatric patients with
      invasive pneumococcal disease.
AB  - Serotype-specific protective immunity in pediatric patients with invasive
      pneumococcal disease (IPD) has not been fully investigated. To determine the
      protective immunity to the infecting serotype, the serotype-specific
      immunoglobulin G (IgG) levels and opsonization indices (OIs) were examined in 24
      Japanese pediatric patients whose serum was collected within one month of an IPD
      episode between May 2008 and June 2011. The median age (range) of IPD patients
      was 17 (10-108) months and 63% were boys. In all 17 patients tested, the levels
      of serotype-specific IgG to the infecting serotype were higher than 0.2 MUg/ml,
      but the OIs to the infecting serotype were <8. The avidities of 19F- or 6B
      specific IgG in patients with levels higher than 5.0 MUg/ml, but with
      undetectable OIs, were confirmed to be lower than those in patients with high
      OIs. Our data demonstrated that although the levels of serotype-specific IgG to
      the infecting serotype were higher than 0.2 MUg/ml in sera of pediatric patients
      with IPD, the OIs were low one month after the IPD episode. Low opsonic
      activities in these patients may, in part, be explained by the low avidity of
      serotype-specific IgG.

PMID- 23153441
TI  - Comprehensive evaluation of the adenovirus/alphavirus-replicon chimeric vector
      based vaccine rAdV-SFV-E2 against classical swine fever.
AB  - Classical swine fever (CSF) is an economically important, highly contagious swine
      disease caused by classical swine fever virus (CSFV). Marker vaccines and
      companion serological diagnostic tests are thought to be a promising strategy for
      future control and eradication of CSF. Previously, we have demonstrated that an
      adenovirus-vectored Semliki forest virus replicon construct expressing the E2
      glycoprotein from CSFV, rAdV-SFV-E2, induced sterile immunity against a lethal
      CSFV challenge. In this study, we further evaluated the vaccine with respect to
      its safety, number and dose of immunization, and effects of maternally derived
      antibodies, re-immunization of the vaccine or co-administration with pseudorabies
      vaccine on the vaccine efficacy. The results showed that: (1) the vaccine was
      safe for mice, rabbits and pigs; (2) two immunizations with a dose as low as
      6.25*10(5) TCID(50) or a single immunization with a dose of 10(7) TCID(50) rAdV
      SFV-E2 provided complete protection against a lethal CSFV challenge; (3)
      maternally derived antibodies had no inhibitory effects on the efficacy of the
      vaccine; (4) the vaccine did not induce interfering anti-vector immunity; and (5)
      co-administration of rAdV-SFV-E2 with a live pseudorabies vaccine induced
      antibodies and protection indistinguishable from immunization with either vaccine
      administered alone. Taken together, the chimeric vaccine represents a promising
      marker vaccine candidate for control and eradication of CSF.

PMID- 23153442
TI  - Acinetobacter baumannii rOmpA vaccine dose alters immune polarization and
      immunodominant epitopes.
AB  - BACKGROUND: The rOmpA vaccine has been shown to protect mice from lethal
      infection caused by extreme-drug-resistant (XDR) Acinetobacter baumannii. The
      role of dose in immunology of the rOmpA vaccine was explored. METHODS: Mice were
      vaccinated with various doses of rOmpA plus aluminum hydroxide (Al(OH)(3))
      adjuvant. The impact of dose on antibody titers, cytokine production, and
      immunodominant epitopes was defined. RESULTS: Anti-rOmpA IgG and IgG subtype
      titers were higher at larger vaccine doses (30 and 100 MUg vs. 3 MUg). The 3 MUg
      dose induced a balanced IFN-gamma-IL-4 immune response while the 100 MUg dose
      induced a polarized IL-4/Type 2 response. Epitope mapping revealed distinct T
      cell epitopes that activated IFN-gamma-, IL-4-, and IL-17-producing splenocytes.
      Vaccination with the 100 MUg dose caused epitope spreading among IL-4-producing
      splenocytes, while it induced fewer reactive epitopes among IFN-gamma-producing
      splenocytes. CONCLUSIONS: Vaccine dose escalation resulted in an enhanced Type 2
      immune response, accompanied by substantial IL-4-inducing T cell epitope
      spreading and restricted IFN-gamma-inducing epitopes. These results inform
      continued development of the rOmpA vaccine against A. baumannii, and also are of
      general importance in that they indicate that immune polarization and epitope
      selectivity can be modulated by altering vaccine dose.

PMID- 23153444
TI  - The role of non-viral antigens in the cotton rat model of respiratory syncytial
      virus vaccine-enhanced disease.
AB  - In the 1960s, infant immunization with a formalin-inactivated respiratory
      syncytial virus (FI-RSV) vaccine candidate caused enhanced respiratory disease
      (ERD) following natural RSV infection. Because of this tragedy, intensive effort
      has been made to understand the root causes of how the FI-RSV vaccine induced a
      pathogenic response to subsequent RSV infection in vaccinees. A well-established
      cotton rat model of FI-RSV vaccine-enhanced disease has been used by numerous
      researchers to study the mechanisms of ERD. Here, we have dissected the model and
      found it to have significant limitations for understanding FI-RSV ERD. This view
      is shaped by our finding that a major driver of lung pathology is cell-culture
      contaminants, although FI-RSV immunization and RSV challenge serve as co-factors
      to exacerbate disease. Specifically, non-viral products from the vaccine and
      challenge preparations that are devoid of RSV give rise to alveolitis, which is
      considered a hallmark of FI-RSV ERD in the cotton rat model. Although FI-RSV
      immunization and RSV challenge promote more severe alveolitis, they also drive
      stronger cellular immune responses to non-viral antigens. The severity of
      alveolitis is associated with T cells specific for non-viral antigens more than
      with T cells specific for RSV. These results highlight the limitations of the
      cotton rat ERD model and the need for an improved animal model to evaluate the
      safety of RSV vaccine candidates.

PMID- 23153443
TI  - Safety and immunogenicity of recombinant Rift Valley fever MP-12 vaccine
      candidates in sheep.
AB  - The safety and immunogenicity of two authentic recombinant (ar) Rift Valley fever
      (RVF) viruses, one with a deletion in the NSs region of the S RNA segment (arMP
      12DeltaNSs16/198) and the other with a large deletion of the NSm gene in the pre
      Gn region of the M RNA segment (arMP-12DeltaNSm21/384) of the RVF MP-12 vaccine
      virus were tested in crossbred ewes at 30-50 days of gestation. First, we
      evaluated the neutralizing antibody response, measured by plaque reduction
      neutralization (PRNT(80)), and clinical response of the two viruses in groups of
      four ewes each. The virus dose was 1*10(5)plaque forming units (PFU). Control
      groups of four ewes each were also inoculated with a similar dose of RVF MP-12 or
      the parent recombinant virus (arMP-12). Neutralizing antibody was first detected
      in 3 of 4 animals inoculated with arMP-12DeltaNSm21/384 on Day 5 post inoculation
      and all four animals had PRNT(80) titers of >=1:20 on Day 6. Neutralizing
      antibody was first detected in 2 of 4 ewes inoculated with arMP-12DeltaNSs16/198
      on Day 7 and all had PRNT(80) titers of >=1:20 on Day 10. We found the mean
      PRNT(80) response to arMP-12DeltaNSs16/198 to be 16- to 25-fold lower than that
      of ewes inoculated with arMP-12DeltaNSm21/384, arMP-12 or RVF MP-12. No abortions
      occurred though a single fetal death in each of the arMP-12 and RVF MP-12 groups
      was found at necropsy. The poor PRNT(80) response to arMP-12DeltaNSs16/198 caused
      us to discontinue further testing of this candidate and focus on arMP
      12DeltaNSm21/384. A dose escalation study of arMP-12DeltaNSm21/384 showed that
      1*10(3)plaque forming units (PFU) stimulate a PRNT(80) response comparable to
      doses of up to 1*10(5)PFU of this virus. With further study, the arMP
      12DeltaNSm21/384 virus may prove to be a safe and efficacious candidate for a
      livestock vaccine. The large deletion in the NSm gene may also provide a negative
      marker that will allow serologic differentiation of naturally infected animals
      from vaccinated animals.

PMID- 23153445
TI  - Effectiveness of influenza vaccination in elderly diabetic patients: a
      retrospective cohort study.
AB  - PURPOSE: Studies regarding the clinical benefits of influenza vaccination in
      diabetic patients are limited. This study evaluated if the elderly diabetic
      patients who have had influenza vaccination would have benefits such as reduced
      medical care and mortality. METHODS: We used the universal insurance claims data
      from 2001 to 2009 in Taiwan to identify annual elderly patients with diabetes
      cohorts with (N=4454) and without (N=4571) influenza vaccination. The risk of
      developing pneumonia or influenza, respiratory failure, intensive care,
      hospitalization, and mortality were measured and compared between cohorts within
      one year of follow-up. RESULTS: The vaccine cohort had lower incidences of
      pneumonia or influenza and respiratory failure compared with the non-vaccine
      cohort. More importantly, the vaccine cohort had a hospitalization rate that was
      11% less than the non-vaccine cohort (29.6 vs. 33.1 per 100 person-years) with an
      adjusted hazard ratio (HR) of 0.88 (95% CI 0.81-0.96). The vaccine cohort was
      also less likely to be admitted to the intensive care unit (ICU) [0.58 vs. 2.05
      per 100 person-year; adjusted HR 0.30 (95% CI 0.19-0.47)] and less likely to
      expire [3.13 vs. 7.96 per 100 person-year; adjusted HR 0.44 (95% CI 0.36-0.54)].
      Influenza vaccination reduced the hospitalization cost by 1282.6 USD, compared
      with patients without influenza vaccination (95% CI -2210.3, -354.8). CONCLUSION:
      Influenza vaccination is associated with a reduced risk of morbidity,
      hospitalization, ICU admissions, and mortality. In addition, the hospitalization
      cost is reduced.

PMID- 23153446
TI  - Reprint of: Serotyping and antibiotic susceptibility of Streptococcus pneumoniae
      strains isolated in Algeria from 2001 to 2010.
AB  - INTRODUCTION: Pneumococcal infections are a major public health problem because
      of the virulence of this bacterium and its ability to develop resistance.
      MATERIAL AND METHOD: Two hundred and ninety-four strains of Streptococcus
      pneumoniae were isolated from sterile (56.8%) and non-sterile samples (43.2%),
      from January 2001 to July 2010. RESULTS: The interpretation of antibiotic
      susceptibility testing, according to CLSI criteria (M100-S21 2011), yielded a
      25.2% overall resistance to penicillin, with 23.5% of strains isolated from CSF
      (meningitis), and only 1.7% in other samples. Resistance to cefotaxime was 8.1%
      (including 4.4% at a high level). The most common serotypes were: 14 (19.5%), 23F
      (9.7%), 6B (9.3%), 19F (5.4%), and serotype 1 (5%). The percentage of these
      serotypes isolated from normally sterile sites in children under 5 years of age
      was 31.25% for 14, 10.4% for 23F, 8.3% for 19F, 6.25% for 6B, and 4.2% for
      serotype 1. The theoretical vaccinal coverage against invasive infections in
      children under 2 years of age was 61.5%, 69.2%, and 76.9% for the 7-valent, 10
      valent, and 13-valent conjugate vaccines, respectively. Penicillin non
      susceptible Streptococcus pneumoniae (PNSP) strains accounted for 67.1, 68.6, and
      72.8% for each of these three vaccines. CONCLUSION: There was a variation of
      serotype rates compared to previous studies. The increase in pneumococcal
      antibiotic resistance is concerning, particularly for the treatment of
      pneumococcal infections in children and infants. Pneumococcal vaccination is not
      compulsory yet in Algeria.

PMID- 23153447
TI  - Immune evasion strategies of flaviviruses.
AB  - Flavivirus is a genus of the family Flaviviridae. It includes West Nile virus
      (WNV), dengue virus (DENV), yellow fever virus (YFV), Japanese encephalitis virus
      (JEV), tick-borne encephalitis virus (TBEV), and several other viruses which lead
      to extensive morbidity and mortality in humans. To establish infection and
      replication in the hosts, flaviviruses have evolved a variety of strategies to
      modulate the host's immune responses. In this review, the strategies employed by
      flaviviruses to evade the innate and adaptive immunity of host are summarized
      based on current studies, with a major focus on the inhibition of interferon,
      complement, natural killer (NK) cell, B cell, and T cell responses. This review
      aims to provide an overview of the current understanding for the mechanisms used
      by flaviviruses to escape the host's immune response, which will facilitate the
      future studies on flavivirus pathogenesis and the development of anti-flavivirus
      therapeutics.

PMID- 23153448
TI  - Immune responses and protection in children in developing countries induced by
      oral vaccines.
AB  - Oral mucosal vaccines have great promise for generating protective immunity
      against intestinal infections for the benefit of large numbers of people
      especially young children. There however appears to be a caveat since these
      vaccines have to overcome the inbuilt resistance of mucosal surfaces and
      secretions to inhibit antigen stimulation and responses. Unfortunately, these
      vaccines are not equally immunogenic nor protective in different populations.
      When compared to industrialized countries, children living in developing
      countries appear to have lower responses, but the reasons for these lowered
      responses are not clearly defined. The most likely explanations relate to
      undernutrition, micronutrient deficiencies, microbial overload on mucosal
      surfaces, alteration of microbiome and microbolom and irreversible changes on the
      mucosa as well as maternal antibodies in serum or breast milk may alter the
      mucosal pathology and lower immune responses to interventions using oral
      vaccines. The detrimental effect of adverse environment and malnutrition may
      bring about irreversible changes in the mucosa of children especially in the
      first 1000 days of life from conception to after birth and up to two years of
      age. This review aims to summarize the information available on lowered immune
      responses to mucosal vaccines and on interventions that may help address the
      constraints of these vaccines when they are used for children living under the
      greatest stress and under harmful adverse circumstances.

PMID- 23153449
TI  - Safety and immunogenicity of a Sf9 insect cell-derived respiratory syncytial
      virus fusion protein nanoparticle vaccine.
AB  - OBJECTIVE: We performed a Phase 1 randomized, observer-blinded, placebo
      controlled trial to evaluate the safety and immunogenicity of a recombinant
      respiratory syncytial virus (RSV) fusion (F) protein nanoparticle vaccine.
      METHODS: Six formulations with (5, 15, 30 and 60 MUg) and without (30 and 60 MUg)
      aluminum phosphate (AdjuPhos) were administered intramuscularly on day 0 and 30
      in a dose escalating fashion to healthy adults 18-49 years of age. Solicited and
      unsolicited events were collected through day 210. Immunogenicity measures taken
      at day 0, 30 and 60 included RSV A and B microneutralization, anti-F IgG,
      antigenic site II peptide and palivizumab competitive antibodies. RESULTS: The
      vaccine was well-tolerated, with no evident dose-related toxicity or attributable
      SAEs. At day 60 both RSV A and B microneutralization was significantly increased
      in vaccinees versus placebo. Across all vaccinees there was a 7- to 19-fold
      increase in the anti-F IgG and a 7- to 24-fold increase in the antigenic site II
      binding and palivizumab competitive antibodies. CONCLUSIONS: The RSV F
      nanoparticle vaccine candidate was well tolerated without dose-related increases
      in adverse events. Measures of immunity indicate that neutralization, anti-RSV F
      IgG titers and palivizumab competing antibodies were induced at levels that have
      been associated with decreased risk of hospitalization. NCT01290419.

PMID- 23153451
TI  - Effects of fatty acids on angiogenic activity in the placental extravillious
      trophoblast cells.
AB  - Fatty acids regulate angiogenesis although no such information is available in
      first trimester placental trophoblast cells despite the fact that angiogenesis is
      a critical step involving these cells in early placentation. We investigated
      effects of different fatty acids on angiogenesis, their uptake and metabolism and
      expression of lipid metabolic genes in first trimester placental trophoblast
      cells using HTR-8/SVneo cell line. Fatty acid uptake by these cells exhibited a
      saturable kinetics. Uptake of AA was consistently greater compared with that of
      EPA and DHA throughout the incubation period of 180 min. Use of triacsin C, an
      inhibitor of acyl-CoA synthetase, significantly inhibited fatty acid uptake as
      well as fatty acid induced cell proliferation in these cells. Angiogenic effect
      (as measured by tube formation) of these fatty acids was in the following order
      DHA> EPA> AA> OA. Angiogenic effect of these fatty acids (AA, EPA, OA) was
      significantly decreased in ANGPTL4 knocked down cells, indicating ANGPTL4 may be
      involved at least in part in fatty acid induced angiogenesis. In addition, these
      fatty acids altered expression of several lipid metabolic genes such as ADRP,
      FABP4, FABP3, and COX-2 those are involved in angiogenesis. All these data
      suggest that fatty acids regulate angiogenic processes in these cells via
      different mechanisms.

PMID- 23153450
TI  - Adsorption of recombinant poxvirus L1-protein to aluminum hydroxide/CpG vaccine
      adjuvants enhances immune responses and protection of mice from vaccinia virus
      challenge.
AB  - The stockpiling of live vaccinia virus vaccines has enhanced biopreparedness
      against the intentional or accidental release of smallpox. Ongoing research on
      future generation smallpox vaccines is providing key insights into protective
      immune responses as well as important information about subunit-vaccine design
      strategies. For protein-based recombinant subunit vaccines, the formulation and
      stability of candidate antigens with different adjuvants are important factors to
      consider for vaccine design. In this work, a non-tagged secreted L1-protein, a
      target antigen on mature virus, was expressed using recombinant baculovirus
      technology and purified. To identify optimal formulation conditions for L1, a
      series of biophysical studies was performed over a range of pH and temperature
      conditions. The overall physical stability profile was summarized in an empirical
      phase diagram. Another critical question to address for development of an
      adjuvanted vaccine was if immunogenicity and protection could be affected by the
      interactions and binding of L1 to aluminum salts (Alhydrogel) with and without a
      second adjuvant, CpG. We thus designed a series of vaccine formulations with
      different binding interactions between the L1 and the two adjuvants, and then
      performed a series of vaccination-challenge experiments in mice including
      measurement of antibody responses and post-challenge weight loss and survival. We
      found that better humoral responses and protection were conferred with vaccine
      formulations when the L1-protein was adsorbed to Alhydrogel. These data
      demonstrate that designing vaccine formulation conditions to maximize antigen
      adjuvant interactions is a key factor in smallpox subunit-vaccine immunogenicity
      and protection.

PMID- 23153452
TI  - Knowledge and practice among Hong Kong oncology nurses in the management of
      chemotherapy-induced nausea and vomiting.
AB  - PURPOSE: To examine nurses' roles in the prevention and management of
      chemotherapy-induced nausea and vomiting (CINV), and to identify their related
      educational needs. METHODS: This was a descriptive cross-sectional study with a
      self-reported survey completed by 103 oncology nurses caring for and
      administering chemotherapy to cancer patients in the department of oncology in
      three Hong Kong public hospitals. The survey was developed to identify key issues
      pertinent to the role of nurses in managing CINV. Data were collected from the
      following areas (a) demographics, (b) assessment of CINV, (c) CINV management and
      (d) barriers and facilitators to good CINV practice. RESULTS: Only a third of
      respondents performed a CINV assessment before starting chemotherapy, and more
      than 40% reported that the use of a standardised assessment tool was uncommon.
      Nearly half recognised that they had inadequate knowledge of different aspects of
      CINV, but the majority could clearly state the most common pharmacological agents
      used to treat chemotherapy-induced nausea (88.3%) and vomiting (87.4%). The
      barriers respondents most frequently encountered in CINV prevention and
      management were lack of time and a heavy workload. Adopting a standardised CINV
      assessment tool and management protocol together with further professional
      training were identified as the major facilitators in improving CINV prevention
      and management. CONCLUSIONS: Respondents perceived their knowledge of CINV
      prevention and management as inadequate. There is a need to adopt a standardised
      assessment tool, to develop a management protocol and to introduce further
      professional training to meet the expanding needs of both patients and nurses.

PMID- 23153453
TI  - Toxicities, complications, and clinical encounters during intraperitoneal
      chemotherapy in 17 women with ovarian cancer.
AB  - PURPOSE OF THE RESEARCH: Intraperitoneal (IP) chemotherapy is a viable and
      superior treatment to standard intravenous (IV) chemotherapy in women with small
      volume residual ovarian cancer following optimal debulking. Despite this clinical
      advantage, widespread adoption of the treatment regimen has been hampered by
      concerns related to toxicities and complications. The purpose of this descriptive
      study was to describe nursing implications related to toxicities, complications
      and clinical encounters in 17 women with ovarian cancer who received IP
      chemotherapy. METHODS AND SAMPLE: Women with ovarian cancer who received IP
      chemotherapy at one NCI-designated comprehensive cancer center were accrued. Data
      related to IP chemotherapy summary, clinical encounters and admissions were
      obtained through comprehensive chart audits. KEY RESULTS: Common treatment
      related toxicities included nausea and vomiting, fatigue, hypomagnesia, pain,
      neuropathy, anemia, and constipation. Reasons for dose-modifications were multi
      factorial, and were primarily related to catheter complications and chemotherapy
      toxicities. The number of clinical encounters was high, and they were primarily
      related to admissions for inpatient IP chemotherapy and follow-up clinic visits.
      CONCLUSIONS: Treatment-related toxicities and complications were common in women
      with ovarian cancer who received IP chemotherapy. Use of IP chemotherapy results
      in multiple clinical encounters, such as outpatient clinic visits and inpatient
      admissions. Nursing is a critical part of the interdisciplinary approach in
      caring for women treated with IP chemotherapy. Interdisciplinary teams with high
      levels of knowledge and skills related to IP chemotherapy administration are
      needed to manage treatment-related toxicities and complications, and support
      multiple clinical encounters during treatment.

PMID- 23153454
TI  - Chromoblastomycosis caused by Fonsecaea: clinicopathology, susceptibility and
      molecular identification of seven consecutive cases in Southern China.
AB  - The clinicopathological and microbiological features of chromoblastomycosis
      caused by Fonsecaea pedrosoi or Fonsecaea monophora are summarized. Four F.
      monophora and three F. pedrosoi strains were isolated from seven consecutive
      chromoblastomycosis patients and identified by genetic analysis between 2004 and
      2012 in a teaching hospital in southern China. Six strains were sensitive to
      voriconazole, itraconazole and terbinafine using E-test and Neo-Sensitabs. Six
      patients healed after oral itraconazole or terbinafine, and one was lost to
      follow up. Internal transcribed spacer sequence is sufficient for species
      delimitation of Fonsecaea, and the Neo-Sensitabs test and E-test are comparable
      in their susceptibility testing. Itraconazole and/or terbinafine may be the
      preferred treatment for this chromoblastomycosis. 

PMID- 23153456
TI  - IFNalpha converts IL-22 into a cytokine efficiently activating STAT1 and its
      downstream targets.
AB  - Besides their antiviral activity, type I Interferons (IFN) display context
      specific immunomodulation. In contrast to long-known IFNalpha/beta, Interleukin
      (IL)-22 is an anti-bacterial, largely tissue protective cytokine that recently
      gained attention. Herein, cellular IFNalpha/IL-22 interactions are investigated.
      We report that pre-conditioning of epithelial cells with IFNalpha initiated
      dramatic changes in IL-22 signaling normally dominated by signal transducer and
      activator of transcription (STAT)-3. Specifically, by using human DLD1 colon
      epithelial/carcinoma cells we demonstrate that, upon IFNalpha, IL-22 converts
      into a cytokine robustly activating STAT1 and its downstream pro-inflammatory
      targets CXCL9, CXCL10, and inducible nitric oxide synthase (iNOS). Accordingly,
      only after IFNalpha pre-incubation was IL-22-induced STAT1 binding to the CXCL10
      promoter detectable. Using the viral mimic polyinosinic:polycytidylic acid and
      the IFNalpha/beta antagonist B18R we furthermore demonstrate the capability of
      endogenous IFN to promote IL-22-induced STAT1 activation and expression of
      CXCL10. IL-22-induced STAT1 activation subsequent to IFNalpha priming became
      likewise apparent in human Caco2 colon epithelial/carcinoma cells, HepG2 hepatoma
      cells, and primary keratinocytes. Current observations may relate to
      characteristics of IFNalpha/beta in clinical therapy and expose margins of tissue
      protection by IL-22 application.

PMID- 23153455
TI  - Overexpression of ATP-binding cassette transporter ABCG2 as a potential mechanism
      of acquired resistance to vemurafenib in BRAF(V600E) mutant cancer cells.
AB  - Melanoma is the most serious type of skin cancer with a high potential for
      metastasis and very low survival rates. The discovery of constitutive activation
      of the BRAF kinase caused by activating BRAF(V600E) kinase mutation in most
      melanoma patients led to the discovery of the first potent BRAF(V600E) signaling
      inhibitor, vemurafenib. Vemurafenib was effective in treating advanced melanoma
      patients and was proposed for the treatment of other BRAF(V600E) mutant cancers
      as well. Unfortunately, the success of vemurafenib was hampered by the rapid
      development of acquired resistance in different types of BRAF(V600E) mutant
      cancer cells. It becomes important to identify and evaluate all of the potential
      mechanisms of cellular resistance to vemurafenib. In this study, we characterized
      the interactions of vemurafenib with three major ATP-binding cassette (ABC)
      transporters, ABCB1, ABCC1 and ABCG2. We found that vemurafenib stimulated the
      ATPase activity and potently inhibited drug efflux mediated by ABCB1 and ABCG2.
      Vemurafenib also restored drug sensitivity in ABCG2-overexpressing cells.
      Moreover, we revealed that in the presence of functional ABCG2, BRAF kinase
      inhibition by vemurafenib is reduced in BRAF(V600E) mutant A375 cells. Taken
      together, our findings indicate that ABCG2 confers resistance to vemurafenib in
      A375 cells, suggesting involvement of this transporter in acquired resistance to
      vemurafenib. Thus, combination chemotherapy targeting multiple pathways could be
      an effective therapeutic strategy to overcome acquired resistance to vemurafenib
      for cancers harboring the BRAF(V600E) mutation.

PMID- 23153457
TI  - Estrogen receptor beta agonists affect growth and gene expression of human breast
      cancer cell lines.
AB  - Expression of estrogen receptor beta (ERbeta) has been described to reduce growth
      of cancer cell lines derived from hormone-dependent tumors, like breast cancer.
      In this study we tested to what extent two ERbeta agonists, androgen derivative
      3beta-Adiol and flavonoid Liquiritigenin, would affect growth and gene expression
      of different ERbeta-positive human breast cancer cell lines. Under standard cell
      culture conditions, we observed 3beta-Adiol to inhibit growth of MCF-7 cells in a
      dose-dependent manner, whereas growth of BT-474 and MCF-10A cells was suppressed
      by the maximum concentration (100 nM) only. When treated in serum-free medium,
      all cell lines except of MDA-MB-231 were responsive to 1 nM 3beta-Adiol, and ZR75
      1 cells exhibited a dose-dependent antiproliferative response. Providing putative
      mechanisms underlying the observed growth-inhibitory effect, expression of Ki-67
      or cyclins A2 and B1 was downregulated after 3beta-Adiol treatment in all
      responsive lines. In contrast, treatment with lower doses of Liquiritigenin did
      not affect growth. In MCF-7 cells, the highest dose of this flavonoid exerted
      proliferative effects accompanied by increased expression of cyclin B1, PR and
      PS2, indicating unspecific activation of ERalpha. In conclusion, the ERbeta
      agonists tested exerted distinct concentration-dependent and cell line-specific
      effects on growth and gene expression. The observed inhibitory effects of 3beta
      Adiol on breast cancer cell growth encourage further studies on the potential of
      this and other ERbeta agonists as targeted drugs for breast cancer therapy.

PMID- 23153458
TI  - Proteome-wide study of endoplasmic reticulum stress induced by thapsigargin in
      N2a neuroblastoma cells.
AB  - Disturbances in intraluminal endoplasmic reticulum (ER) Ca(2+) concentration
      leads to the accumulation of unfolded proteins and perturbation of intracellular
      Ca(2+) homeostasis, which has a huge impact on mitochondrial functioning under
      normal and stress conditions and can trigger cell death. Thapsigargin (TG) is
      widely used to model cellular ER stress as it is a selective and powerful
      inhibitor of sarcoplasmic/endoplasmic reticulum Ca(2+) ATPases. Here we provide a
      representative proteome-wide picture of ER stress induced by TG in N2a
      neuroblastoma cells. Our proteomics study revealed numerous significant protein
      expression changes in TG-treated N2a cell lysates analysed by two-dimensional
      electrophoresis followed by mass spectrometric protein identification. The
      proteomic signature supports the evidence of increased bioenergetic activity of
      mitochondria as several mitochondrial enzymes with roles in ATP-production,
      tricarboxylic acid cycle and other mitochondrial metabolic processes were
      upregulated. In addition, the upregulation of the main ER resident proteins
      confirmed the onset of ER stress during TG treatment. It has become widely
      accepted that metabolic activity of mitochondria is induced in the early phases
      in ER stress, which can trigger mitochondrial collapse and subsequent cell death.
      Further investigations of this cellular stress response in different neuronal
      model systems like N2a cells could help to elucidate several neurodegenerative
      disorders in which ER stress is implicated.

PMID- 23153459
TI  - Coupling microbial catabolic actions with abiotic redox processes: a new recipe
      for persistent organic pollutant (POP) removal.
AB  - The continuous release of toxic persistent organic pollutants (POPs) into the
      environment has raised a need for effective cleanup methods. The tremendous
      natural diversity of microbial catabolic mechanisms suggests that catabolic
      routes may be applied to the remediation of POP-contaminated fields. A large
      number of the recalcitrant xenobiotics have been shown to be removable via the
      natural catabolic mechanisms of microbes, and detailed biochemical studies of the
      catabolic methods, together with the development of sophisticated genetic
      engineering, have led to the use of synthetic microbes for the bioremediation of
      POPs. However, the steric effects of substituted halogen moieties, microbe
      toxicity, and the low bioavailability of POPs still deteriorate the efficiency of
      removal strategies based on natural and synthetic catabolic mechanisms. Recently,
      abiotic redox processes that induce rapid reductive dehalogenation, hydroxyl
      radical-based oxidation, or electron shuttling have been reasonably coupled with
      microbial catabolic actions, thereby compensating for the drawbacks of biotic
      processes in POP removal. In this review, we first compare the pros and cons of
      individual methodologies (i.e., the natural and synthetic catabolism of microbes
      and the abiotic processes involving zero-valent irons, advanced oxidation
      processes, and small organic stimulants) for POP removal. We then highlight
      recent trends in coupling the biotic-abiotic methodologies and discuss how the
      processes are both feasible and superior to individual methodologies for POP
      cleanup. Cost-effective and environmentally sustainable abiotic redox actions
      could enhance the microbial bioremediation potential for POPs.

PMID- 23153460
TI  - Enhancing stem cell survival in vivo for tissue repair.
AB  - The ability to use progenitor cells for regenerative medicine remains an evolving
      but elusive clinical goal. A serious obstacle towards widespread use of stem
      cells for tissue regeneration is the challenges that face these cells when they
      are placed in vivo into a wound for therapy. These environments are hypoxic,
      acidic, and have an upregulation of inflammatory mediators creating a region that
      is hostile towards cellular survival. Within this environment, the majority of
      progenitor cells undergo apoptosis prior to participating in lineage
      differentiation and cellular integration. In order to maximize the clinical
      utility of stem cells, strategies must be employed to increase the cell's ability
      to survive in vivo through manipulation of both the stem cell and the surrounding
      environment. This review focuses on current advances and techniques being used to
      increase in vivo stem cell survival for the purpose of tissue regeneration. 

PMID- 23153461
TI  - [Audiological care should be reformed].

PMID- 23153462
TI  - [Acute medical coordination dispatch centres will be key partners, allowing more
      people to survive out-of-hospital cardiac arrests].

PMID- 23153463
TI  - [Renewal of a hearing aid is a medical task].
AB  - A 67 year-old man was known to have a right-sided hearing loss with a normal
      discrimination score (DS) and was treated with a hearing aid (HA) in the right
      ear. An MRI-scan was normal. In 2006 and 2010 the HA was renewed at a private
      hearing aid clinic. No DS was performed. At the audiology clinic we found a
      masked DS of 0% and progression of the hearing loss. An MRI-scan revealed a
      vestibular schwannoma (VS) on the right side. The patient was fitted with an HA
      in the left ear and MRI-scans every six months. A masked DS could have revealed
      the VS and correct treatment thus could have been initiated sooner.

PMID- 23153464
TI  - [Vestibular schwannoma as cause of sudden unilateral deafness and tinnitus].
AB  - Vestibular schwannoma (VS) is a rare disorder. In Denmark,  approximately 120
      patients are being diagnosed yearly. This is a case report of a 29-year-old
      female patient with VS, which began with sudden deafness 6-7 years ago. The
      correct diagnosis was made relatively late.

PMID- 23153465
TI  - [Health professional operators at dispatch centres shall ensure identification of
      cardiac arrest and initiate counselling by telephone].
AB  - Denmark has introduced health professional operators (HPO) at the dispatch
      centres to ensure early identification of cardiac arrest and earlier initiation
      of cardiopulmonary resuscitation (CPR) to improve survival. Communicative skills
      and personal competences are important, and the HPOs' medical background will
      probably lead to better triage of patients. Their use of a protocol, leads to a
      more frequent recognition of cardiac arrest and contributes to better CPR
      guidance. A common national training for all the HPOs' has been implemented and
      future guidance might include video-transmission.

PMID- 23153466
TI  - [Pilonidal disease is a benign condition].
AB  - Malignant transformation in pilonidal disease is rare and never reported in
      Denmark. There are 75 cases in the literature, mostly squamous cell carcinoma.
      The cost-benefit of routine histological examination of specimens from pilonidal
      surgery is questionable, as malignancy is extremely rare. Due to increased
      incidence of cancer, specimens from patients with many years of pilonidal
      disease, known immunodeficiencies and/or human papillomavirus infection or
      clinical abnormal presentation, should always be investigated.

PMID- 23153467
TI  - [Characteristics, diagnosis and therapy of patients with autoimmune hepatitis].
AB  - Autoimmune hepatitis is a relatively rare disease that may lead to rapidly
      progressing liver cirrhosis and even fulminant liver failure, if diagnosis and
      treatment is delayed or ineffective. Diagnosing the disease can be challenging,
      and one in five patients respond insufficiently to standard treatment. Patients,
      who are diagnosed late in the disease course or only respond partly to medical
      treatment, are at high risk of developing severe liver insufficiency. This
      article summarizes the present knowledge and evidence regarding diagnostics,
      therapy and disease course.

PMID- 23153468
TI  - [Mirtazapine versus other antidepressive agents for depression].
AB  - A Cochrane analysis compared efficacy and side effects of mirtazapine with other
      antidepressants. After six weeks of treatment no reliable difference of efficacy
      between mirtazapine, selective serotonin reuptake inhibitors (SSRI),
      noradrenaline reuptake inhibitors or tricyclic antidepressants was found. The
      side effects like increased sleep and weight gain were compared by treatment with
      mirtazapine and treatment with SSRI antidepressants. The very fact of the sleep
      effect and the fast onset of action have probably increased the effect size
      compared with SSRI antidepressants. The results of the Cochrane analysis cannot
      for certain be generalized to inpatients, as other studies have found tricyclic
      antidepressants to be especially effective.

PMID- 23153469
TI  - [Family occurrence of steroid-sensitive idiopathic nephrotic syndrome].
AB  - Nephrotic syndrome (NS) presented within three weeks in siblings aged six and ten
      years. Both children experienced proteinuria, hypoalbuminaemia and oedema, with
      the most pronounced symptoms in the older. Standard treatment with prednisolone
      led to remission of the nephrotic syndrome in the younger, whereas the older
      required additional therapy with tacrolismus before remission. In view of the low
      incidence of NS in children, a near simultaneously onset in two siblings must
      lead to genetic elucidation. Genetic disorders and other causes of childhood NS
      are discussed.

PMID- 23153470
TI  - [Bullectomy of giant bullae gave significant improvement of lung function].
AB  - A 49-year-old male smoker experienced acute deterioration of a progressive
      breathlessness. Spontaneous pneumothorax was diagnosed, and drainage was applied.
      Subsequent computed tomography revealed severe bilateral emphysematous bullae
      with right-sided predominance, and basal atelectasis. A lung function test showed
      severe obstructive disease. Right-sided bullectomy was performed through anterior
      thoracotomy with removal of giant bullae. Postoperative examination revealed
      markedly improved lung function and expansion of right-sided, previously
      consolidated lung tissue.

PMID- 23153471
TI  - Subcutaneous phaeohyphomycosis due to Curvularia lunata in a renal transplant
      patient.
AB  - BACKGROUND: Phaeohyphomycosis is defined as an infection caused by melanized
      fungi. It predominates in tropical climate and is currently classified as
      superficial, allergic, central nervous system or lung infections, and
      disseminated. Curvularia is one of the many genres which can cause this disease.
      Phialophora, Alternaria and Exophiala are more commonly isolated from
      subcutaneous lesions. CASE REPORT: A 25-year-old male, renal transplant recipient
      presents with an ulcer on his left leg. Subcutaneous phaeohyphomycosis due to
      Curvularia lunata was diagnosed based on mycological examination and
      histopathological findings. He was successfully treated with systemic
      itraconazole and surgical resection. CONCLUSION: The incidence of
      phaeohyphomycosis has increased in the last decades, especially in
      immunosuppressed individuals; nevertheless the number of cases does not allow for
      therapeutic controlled trials to be performed. Hence, we consider that it is
      important to communicate individual cases and reviews of the literature, to
      increase awareness of the disease, its clinical presentation and response to
      treatment.

PMID- 23153472
TI  - Acupuncture in the treatment of obesity: a narrative review of the literature.
AB  - Obesity is one of the leading health risk factors worldwide and is associated
      with several other risk factors and health problems including type 2 diabetes
      mellitus, cardiovascular disease and malignancies. Current conventional
      therapeutic strategies for obesity cannot achieve adequate weight control in all
      patients, so complementary types of treatment are also performed. Acupuncture,
      one of the oldest healing practices, represents the most rapidly growing
      complementary therapy which is recognised by both the National Institutes of
      Health and the WHO. A previous review concluded that acupuncture was superior to
      lifestyle advice, to sham acupuncture and to conventional medication. In this
      narrative review, the possible mechanisms of actions and the results of recent
      experimental and clinical studies with different forms of acupuncture (eg, body,
      auricular, manual and electroacupuncture) are presented. In particular, the
      effects of acupuncture on anorexigenic and orexigenic peptides, insulin
      resistance, lipid metabolism and inflammatory markers are discussed. Both
      experimental and clinical current data suggest that acupuncture exerts beneficial
      effects on the mechanisms of obesity. Some data suggest that electroacupuncture
      may be more effective than manual acupuncture; however, the most effective
      frequency remains controversial. Combination of different forms of acupuncture
      with diet and exercise seems to be necessary for achieving and maintaining weight
      loss.  Further prospective clinical trials are needed to establish the
      effectiveness of this complementary method for obesity treatment.

PMID- 23153473
TI  - Ongoing outbreak of an acute muscular Sarcocystis-like illness among travellers
      returning from Tioman Island, Malaysia, 2011-2012.
AB  - As of 4 November, 2012, 100 patients with an acute muscular Sarcocystis-like
      illness associated with travel to Tioman Island, Malaysia, have been identified.
      Thirty-five travelled there mostly during July and August 2011 and 65 mostly
      during July and August 2012, suggesting an ongoing outbreak. Epidemiological
      investigations are ongoing. Public health agencies and practicing clinicians
      should be aware of this rarely-reported disease in humans and consider it as
      differential diagnosis in travellers returning from Tioman Island.

PMID- 23153474
TI  - Recurrent pyelonephritis due to NDM-1 metallo-beta-lactamase producing
      Pseudomonas aeruginosa in a patient returning from Serbia, France, 2012.
AB  - We describe the first isolation in France of a New-Delhi metallo-beta-lactamase-1
      (NDM-1) producing Pseudomonas aeruginosa. In March 2012, a patient with history
      of prior hospitalisation in Serbia was diagnosed in France with acute
      pyelonephritis due to NDM-1 producing P. aeruginosa. Clinical and microbiological
      cure was obtained under appropriate antibiotic treatment. Two months later, she
      presented with a recurrence due to the same bacteria, with a favourable
      evolution. During both hospitalisations, contact isolation precautions were
      implemented and no cross-transmission was observed.

PMID- 23153475
TI  - Hospitalisation associated with the 2009 H1N1 pandemic and seasonal influenza in
      Hong Kong, 2005 to 2010.
AB  - Reliable estimates of the morbidity burden caused by the 2009 pandemic influenza
      (pH1N1) are important for assessing the severity of the pandemic. Poisson
      regression models were fitted to weekly numbers of cause-specific hospitalisation
      in Hong Kong from 2005 to 2010. Excess hospitalisation associated with the 2009
      pandemic and seasonal influenza was derived from the model by incorporating the
      proxy variables of weekly proportions of specimens positive for the pandemic
      influenza A(H1N1)pdm09, seasonal influenza A (subtypes H3N2 and H1N1) and B
      viruses. Compared with seasonal influenza, pH1N1 influenza was associated with
      higher hospitalisation rates for acute respiratory disease (ARD) among children
      younger than 18 years and adults aged between 18 and 64 years, but among the
      elderly aged 65 years and older the hospitalisation rates were lower for pH1N1
      than for seasonal H3N2 and H1N1 influenza. Hospitalisation rates for chronic
      diseases associated with pH1N1 influenza were generally higher than those
      associated with seasonal influenza. The reported hospitalised cases with
      laboratory-confirmed pandemic infections accounted for only 16% of pH1N1
      influenza-associated hospitalisations for ARD in the age group 75 years and
      older, and 5-66% of hospitalisations for chronic diseases in those older than 40
      years. The 2009 H1N1 influenza pandemic was associated with a dramatically
      increased risk of hospitalisation among children and young adults. The morbidity
      burden of pandemic was underreported in old people and in those with chronic
      conditions.

PMID- 23153476
TI  - Assessment of the bio-preparedness and of the training of the French hospital
      laboratories in the event of biological threat.
AB  - A national laboratory network 'Biotox-Piratox' was created in 2003 in France with
      the purpose of detecting, confirming and reporting potential biological and
      chemical threat agents. This network is divided into three levels: Level 1 is
      dedicated to the evaluation of risks (biological, chemical, radiological), to
      sampling and packing. Level 2 consists of university and military hospitals, who
      deal with biological specimens, and of environmental and veterinary laboratories,
      who deal with environmental and animal samples. Level 3 comprises national
      reference laboratories and the Jean Merieux biosafety level (BSL)-4 laboratory in
      Lyon. This report presents the results of four bio-preparedness exercises to
      check critical points in the processing of samples. These exercises took place in
      2007, 2009, 2010 and 2011. Each of them consisted of two parts. The first part
      was the identification of an unknown bacterial strain and its susceptibility to
      antibiotics used as a default in case of a bioterrorist event. The second part
      was the detection of Class III microorganisms, mainly by molecular techniques.
      The main lesson learnt in these exercises was that the key to successful
      detection of biological agents in case of a biological threat was standardisation
      and validation of the methods implemented by all the laboratories belonging to
      the network.

PMID- 23153477
TI  - Pre-cachexia and cachexia at diagnosis of stage III non-small-cell lung
      carcinoma: an exploratory study comparing two consensus-based frameworks.
AB  - Despite the development of consensus-based frameworks to define cancer cachexia,
      the validity and usefulness of these frameworks are relatively unknown. The aim
      of the present study was to study the presence of pre-cachexia and cachexia in
      patients with stage III nonsmall-cell lung carcinoma (NSCLC) by using a cancer
      specific framework and a general framework for cachexia, and to explore the
      prognostic value of pre-cachexia and cachexia. In forty patients at diagnosis of
      stage III NSCLC, weight loss, fat-free mass, handgrip strength, anorexia and
      serum biochemistry, assessed before the first chemotherapy, were used to define
      'cancer cachexia' or 'cachexia'. The cancer-specific framework also classified
      for pre-cachexia and refractory cachexia. Additionally, quality of life was
      assessed by the European Organisation for Research and Treatment of Cancer
      Quality of Life Questionnaire C30. Groups were compared using independent t
      tests, ANOVA, Kaplan-Meier and Cox survival analyses. Based on the cancer
      specific framework, pre-cachexia was present in nine patients (23%) and cancer
      cachexia was present in seven patients (18%). Cancer cachexia was associated with
      a reduced quality of life (P = 0.03) and shorter survival (hazard ratio (HR) =
      2.9; P = 0.04). When using the general framework, cachexia was present in eleven
      patients (28%), and was associated with a reduced quality of life (P = 0.08) and
      shorter survival (HR = 4.4; P = 0.001). In conclusion, pre-cachexia and cachexia
      are prevalent in this small population of patients at diagnosis of stage III
      NSCLC. For both frameworks, cachexia appears to be associated with a reduced
      quality of life and shorter survival. Further studies are warranted to more
      extensively explore the validity and prognostic value of these new frameworks in
      cancer patients.

PMID- 23153478
TI  - Diet-induced antisecretory factor prevents intracranial hypertension in a dosage
      dependent manner.
AB  - Intake of specially processed cereal (SPC) stimulates endogenous antisecretory
      factor (AF) activity, and SPC intake has proven to be beneficial for a number of
      clinical conditions. The aim of the present study was to investigate the dosage
      relationship between SPC intake and plasma AF activity and to further correlate
      achieved AF levels to a biological effect. SPC was fed to rats in concentrations
      of 5, 10 or 15% for 2 weeks. A further group was fed 5% SPC for 4 weeks. AF
      activity and the complement factors C3c and factor H were analysed in plasma
      after the feeding period. Groups of rats fed the various SPC concentrations were
      subjected to a standardised freezing brain injury, known to induce increases in
      intracranial pressure (ICP). The AF activity in plasma increased after intake of
      SPC, in a dosage- and time-dependent manner. The complement factors C3c and
      factor H increased in a time-dependent manner. Measurements of ICP in animals fed
      with SPC prior to the brain injury showed that the ICP was significantly lower,
      compared with that of injured rats fed with a standard feed, and that the change
      was dose and time dependent. AF activity increases, in a dosage- and time
      dependent manner, after intake of SPC. The inverse relationship between ICP after
      a head injury and the percentage of SPC in the feed indicate that the protective
      effect is, to a large extent, due to AF.

PMID- 23153480
TI  - Statement regarding the pre and post market assessment of durable, implantable
      ventricular assist devices in the United States: executive summary.
AB  - The incorporation of complex medical device technologies into clinical practice
      is governed by critical oversight of the US Food and Drug Administration. This
      regulatory process requires a judicious balance between assuring safety and
      efficacy, while providing efficient review to facilitate access to innovative
      therapies. Recent contrasting views of the regulatory process have emphasized the
      difficulties in obtaining an optimal balance. Mechanical circulatory support has
      evolved to become an important therapy for patients with advanced heart failure
      with the advent of more durable, implantable ventricular assist devices. The
      regulatory oversight of these new technologies has been difficult owing to the
      complexities of these devices, associated adverse event profile, and severity of
      illness of the intended patient population. Maintaining a regulatory environment
      to foster efficient introduction of safe and effective technologies is critical
      to the success of ventricular assist device therapy and the health of patients
      with advanced heart failure. Physicians representing key surgical and cardiology
      societies, and representatives from the Food and Drug Administration, National
      Heart Lung, and Blood Institute, Centers for Medicare and Medicaid Services,
      Interagency Registry of Mechanically Assisted Circulatory Support, and industry
      partners gathered to discuss relevant issues regarding the current regulatory
      environment assessing ventricular assist devices. The goal of the meeting was to
      explore innovative ways to foster the introduction of technologically advanced,
      safe, and effective ventricular assist devices. The following summary reflects
      opinions and conclusions endorsed by The Society of Thoracic Surgeons, American
      Association for Thoracic Surgery, American Heart Association, Heart Failure
      Society of America, International Society for Heart and Lung Transplantation, and
      the Interagency Registry of Mechanically Assisted Circulatory Support.

PMID- 23153481
TI  - Statement regarding the pre and post market assessment of durable, implantable
      ventricular assist devices in the United States.
AB  - The incorporation of complex medical device technologies into clinical practice
      is governed by critical oversight of the US Food and Drug Administration. This
      regulatory process requires a judicious balance between assuring safety and
      efficacy, while providing efficient review to facilitate access to innovative
      therapies. Recent contrasting views of the regulatory process have emphasized the
      difficulties in obtaining an optimal balance. Mechanical circulatory support has
      evolved to become an important therapy for patients who have advanced heart
      failure with the advent of more durable, implantable ventricular assist devices.
      The regulatory oversight of these new technologies has been difficult owing to
      the complexities of these devices, associated adverse event profile, and severity
      of illness of the intended patient population. Maintaining a regulatory
      environment to foster efficient introduction of safe and effective technologies
      is critical to the success of ventricular assist device therapy and the health of
      patients with advanced heart failure. Physicians representing key surgical and
      cardiology societies, and representatives from the Food and Drug Administration,
      National Heart Lung, and Blood Institute, Centers for Medicare and Medicaid
      Services, Interagency Registry of Mechanically Assisted Circulatory Support, and
      industry partners gathered to discuss relevant issues regarding the current
      regulatory environment assessing ventricular assist devices. The goal of the
      meeting was to explore innovative ways to foster the introduction of
      technologically advanced, safe, and effective ventricular assist devices. The
      following summary reflects opinions and conclusions endorsed by The Society of
      Thoracic Surgeons, American Association for Thoracic Surgery, American Heart
      Association, Heart Failure Society of America, International Society for Heart
      and Lung Transplantation, and Interagency Registry of Mechanically Assisted
      Circulatory Support.

PMID- 23153482
TI  - Neuropsychological profiles of children with aqueductal stenosis and Spina Bifida
      myelomeningocele.
AB  - We compared neuropsychological profiles in children with shunted hydrocephalus
      secondary to aqueductal stenosis (AS), a rare form of congenital hydrocephalus,
      and spina bifida myelomeningocele (SBM), a common form of congenital
      hydrocephalus. Participants were 180 children with shunted hydrocephalus grouped
      according to etiology: SBM (n = 151), AS (n = 29), and typically developing (TD;
      n = 60) individuals. The group with AS performed below the TD group on all tasks
      except for reading, and their overall performance was higher than the group with
      SBM, who had the lowest performance in the sample. Both clinical groups
      significantly differed from the TD group on tasks of spatial function, concept
      formation, motor function, and memory. Performance of the subgroup of AS children
      with normal cerebellum status approximated that of the TD group, while those with
      cerebellar anomalies performed lower than others with AS. Cerebellar
      abnormalities (present in the whole SBM group and in a subset of the AD group)
      are associated with more compromise of cognitive as well as motor function.

PMID- 23153483
TI  - Quality control and fidelity.

PMID- 23153485
TI  - Curvature, lipid packing, and electrostatics of membrane organelles: defining
      cellular territories in determining specificity.
AB  - Whereas some rare lipids contribute to the identity of cell organelles, we focus
      on the abundant lipids that form the matrix of organelle membranes. Observations
      using bioprobes and peripheral proteins, notably sensors of membrane curvature,
      support the prediction that the cell contains two broad membrane territories: the
      territory of loose lipid packing, where cytosolic proteins take advantage of
      membrane defects, and the territory of electrostatics, where proteins are
      attracted by negatively charged lipids. The contrasting features of these
      territories provide specificity for reactions occurring along the secretory
      pathway, on the plasma membrane, and also on lipid droplets and autophagosomes.

PMID- 23153484
TI  - Building complexity: insights into self-organized assembly of microtubule-based
      architectures.
AB  - Successful completion of diverse cellular functions, such as mitosis, positioning
      organelles, and assembling cilia, depends on the proper assembly of microtubule
      based structures. While essentially all of the proteins needed to assemble these
      structures are now known, we cannot explain how even simple features such as size
      and shape are determined. As steps toward filling this knowledge gap, there have
      been several recent efforts toward reconstituting, with purified proteins, the
      basic structural motifs that recur in diverse cytoskeletal arrays. We discuss
      these studies and highlight how they shed light on the self-organized assembly of
      complex and dynamic cytoskeleton-based cellular structures.

PMID- 23153486
TI  - Design principles of protein biosynthesis-coupled quality control.
AB  - The protein biosynthetic machinery, composed of ribosomes, chaperones, and
      localization factors, is increasingly found to interact directly with factors
      dedicated to protein degradation. The coupling of these two opposing processes
      facilitates quality control of nascent polypeptides at each stage of their
      maturation. Sequential checkpoints maximize the overall fidelity of protein
      maturation, minimize the exposure of defective products to the bulk cellular
      environment, and protect organisms from protein misfolding diseases.

PMID- 23153487
TI  - Chromothripsis: chromosomes in crisis.
AB  - During oncogenesis, cells acquire multiple genetic alterations that confer
      essential tumor-specific traits, including immortalization, escape from
      antimitogenic signaling, neovascularization, invasiveness, and metastatic
      potential. In most instances, these alterations are thought to arise
      incrementally over years, if not decades. However, recent progress in sequencing
      cancer genomes has begun to challenge this paradigm, because a radically
      different phenomenon, termed chromothripsis, has been suggested to cause complex
      intra- and interchromosomal rearrangements on short timescales. In this Review,
      we review established pathways crucial for genome integrity and discuss how their
      dysfunction could precipitate widespread chromosome breakage and rearrangement in
      the course of malignancy.

PMID- 23153488
TI  - Silencing by throwing away: a role for chromatin diminution.
AB  - Chromatin diminution during development generates cells with varying genetic
      content within the same organism. Two recent papers demonstrate that in two
      different systems chromatin diminution removes a considerable number of genes
      from somatic cells, thereby restricting their expression to the germline.

PMID- 23153489
TI  - A new direction for gene looping.
AB  - Upon binding to a promoter, RNA polymerase II can synthesize either a coding mRNA
      or a divergently transcribed noncoding RNA. In a recent issue of Science, Tan
      Wong et al. (2012) find that intragenic looping increases the proper orientation
      of RNA polymerase II, reducing the production of divergent noncoding transcripts.

PMID- 23153490
TI  - IRE1, a double-edged sword in pre-miRNA slicing and cell death.
AB  - IRE1alpha, the most conserved transducer of the unfolded protein response, plays
      critical roles in many biological processes and cell fate decisions. Reporting in
      Science, Upton et al. (2012) broadened our understanding of IRE1alpha as a cell
      death executioner, showing that upon ER stress, IRE1alpha degrades microRNAs to
      promote translation of caspase-2.

PMID- 23153491
TI  - Choreographing the axo-dendritic dance.
AB  - The assembly of neuronal synapses in the brain relies on a sophisticated
      bidirectional signal exchange between synaptic partners. In a recent issue of
      Neuron, Ito-Ishida and colleagues (2012) uncover a morphogenetic program
      underlying the formation of presynaptic terminals.

PMID- 23153492
TI  - Arl13b in primary cilia regulates the migration and placement of interneurons in
      the developing cerebral cortex.
AB  - Coordinated migration and placement of interneurons and projection neurons lead
      to functional connectivity in the cerebral cortex; defective neuronal migration
      and the resultant connectivity changes underlie the cognitive defects in a
      spectrum of neurological disorders. Here we show that primary cilia play a
      guiding role in the migration and placement of postmitotic interneurons in the
      developing cerebral cortex and that this process requires the ciliary protein,
      Arl13b. Through live imaging of interneuronal cilia, we show that migrating
      interneurons display highly dynamic primary cilia and we correlate cilia dynamics
      with the interneuron's migratory state. We demonstrate that the guidance cue
      receptors essential for interneuronal migration localize to interneuronal primary
      cilia, but their concentration and dynamics are altered in the absence of Arl13b.
      Expression of Arl13b variants known to cause Joubert syndrome induce defective
      interneuronal migration, suggesting that defects in cilia-dependent interneuron
      migration may in part underlie the neurological defects in Joubert syndrome
      patients.

PMID- 23153493
TI  - Anisotropy of Crumbs and aPKC drives myosin cable assembly during tube formation.
AB  - The formation of tubular structures from epithelial sheets is a key process of
      organ formation in all animals, but the cytoskeletal rearrangements that cause
      the cell shape changes that drive tubulogenesis are not well understood. Using
      live imaging and super-resolution microscopy to analyze the tubulogenesis of the
      Drosophila salivary glands, I find that an anisotropic plasma membrane
      distribution of the protein Crumbs, mediated by its large extracellular domain,
      determines the subcellular localization of a supracellular actomyosin cable in
      the cells at the placode border, with myosin II accumulating at edges where
      Crumbs is lowest. Laser ablation shows that the cable is under increased tension,
      implying an active involvement in the invagination process. Crumbs anisotropy
      leads to anisotropic distribution of aPKC, which in turn can negatively regulate
      Rok, thus preventing the formation of a cable where Crumbs and aPKC are
      localized.

PMID- 23153494
TI  - The NF-kappaB signaling protein Bcl10 regulates actin dynamics by controlling AP1
      and OCRL-bearing vesicles.
AB  - The protein Bcl10 contributes to adaptive and innate immunity through the
      assembly of a signaling complex that plays a key role in antigen receptor and FcR
      induced NF-kappaB activation. Here we demonstrate that Bcl10 has an NF-kappaB
      independent role in actin and membrane remodeling downstream of FcR in human
      macrophages. Depletion of Bcl10 impaired Rac1 and PI3K activation and led to an
      abortive phagocytic cup rich in PI(4,5)P(2), Cdc42, and F-actin, which could be
      rescued with low doses of F-actin depolymerizing drugs. Unexpectedly, we found
      Bcl10 in a complex with the clathrin adaptors AP1 and EpsinR. In particular,
      Bcl10 was required to locally deliver the vesicular OCRL phosphatase that
      regulates PI(4,5)P(2) and F-actin turnover, both crucial for the completion of
      phagosome closure. Thus, we identify Bcl10 as an early coordinator of NF-kappaB
      mediated immune response with endosomal trafficking and signaling to F-actin
      remodeling.

PMID- 23153495
TI  - Sox2 in the dermal papilla niche controls hair growth by fine-tuning BMP
      signaling in differentiating hair shaft progenitors.
AB  - How dermal papilla (DP) niche cells regulate hair follicle progenitors to control
      hair growth remains unclear. Using Tbx18(Cre) to target embryonic DP precursors,
      we ablate the transcription factor Sox2 early and efficiently, resulting in
      diminished hair shaft outgrowth. We find that DP niche expression of Sox2
      controls the migration speed of differentiating hair shaft progenitors.
      Transcriptional profiling of Sox2 null DPs reveals increased Bmp6 and decreased
      BMP inhibitor Sostdc1, a direct Sox2 transcriptional target. Subsequently, we
      identify upregulated BMP signaling in knockout hair shaft progenitors and
      demonstrate that Bmp6 inhibits cell migration, an effect that can be attenuated
      by Sostdc1. A shorter and Sox2-negative hair type lacks Sostdc1 in the DP and
      shows reduced migration and increased BMP activity of hair shaft progenitors.
      Collectively, our data identify Sox2 as a key regulator of hair growth that
      controls progenitor migration by fine-tuning BMP-mediated mesenchymal-epithelial
      crosstalk.

PMID- 23153496
TI  - Single-cell-resolution imaging of the impact of Notch signaling and mitosis on
      segmentation clock dynamics.
AB  - Vertebrate body segmentation is controlled by the segmentation clock, a molecular
      oscillator involving transcriptional oscillations of cyclic genes in presomitic
      mesoderm cells. The rapid and highly dynamic nature of this oscillating system
      has proved challenging for study at the single-cell level. We achieved
      visualization of clock activity with a cellular level of resolution in living
      embryos, allowing direct comparison of oscillations in neighbor cells. We provide
      direct evidence that presomitic mesoderm cells oscillate asynchronously in
      zebrafish Notch pathway mutants. By tracking oscillations in mitotic cells, we
      reveal that a robust cell-autonomous, Notch-independent mechanism resumes
      oscillations after mitosis. Finally, we find that cells preferentially divide at
      a certain oscillation phase, likely reducing the noise generated by cell division
      in cell synchrony and suggesting an intriguing relationship between the mitotic
      cycle and clock oscillation.

PMID- 23153497
TI  - Mechanistic differences in the transcriptional interpretation of local and long
      range Shh morphogen signaling.
AB  - Morphogens orchestrate tissue patterning in a concentration-dependent fashion
      during vertebrate embryogenesis, yet little is known of how positional
      information provided by such signals is translated into discrete transcriptional
      outputs. Here we have identified and characterized cis-regulatory modules (CRMs)
      of genes operating downstream of graded Shh signaling and bifunctional Gli
      proteins in neural patterning. Unexpectedly, we find that Gli activators have a
      noninstructive role in long-range patterning and cooperate with SoxB1 proteins to
      facilitate a largely concentration-independent mode of gene activation. Instead,
      the opposing Gli-repressor gradient is interpreted at transcriptional levels,
      and, together with CRM-specific repressive input of homeodomain proteins,
      comprises a repressive network that translates graded Shh signaling into regional
      gene expression patterns. Moreover, local and long-range interpretation of Shh
      signaling differs with respect to CRM context sensitivity and Gli-activator
      dependence, and we propose that these differences provide insight into how
      morphogen function may have mechanistically evolved from an initially binary
      inductive event.

PMID- 23153498
TI  - [Paralysing lumbar disc herniation: a surgical emergency? Reflexion about a
      series of 24 patients and literature data].
AB  - BACKGROUND AND PURPOSE: Paralysing lumbar disc herniation (LDH): what and when to
      do? Few studies have analyzed the optimal timing of surgery in case of paralysing
      LDH. METHODS: Twenty-four charts were retrospectively reviewed of patients
      suffering of LDH with severe motor deficit. RESULTS: There were 16 men and eight
      women. Mean age was 45.1 years. Seventeen patients suffered of lumbar pain, 15 of
      radicular pain and all of a severe motor deficit, implying mostly the ankle
      flexion (17 patients). LDH was most frequently located at L4/L5 or L5/S1 level.
      Surgery was proposed to all patients at the end of the consultation. Nine
      patients were operated within 48 hours. The mean interval between onset of motor
      deficit and operation was 20 days. The statistical analysis did not reveal any
      significant difference among different prognostic factors between the 17 patients
      with good motor recovery and the seven patients with poor motor recovery. In
      particular the operative delay did not appear to influence the degree of motor
      recovery. Literature review on paralysing LDH provides five published series
      since 1996, including 28 to 116 patients. Two series, including the single
      prospective one, conclude that the degree of recovery of motor function is
      inversely related to the degree and duration of motor deficit. CONCLUSIONS: Our
      retrospective series of 24 operated paralysing LDH did not reveal any prognostic
      factor for motor recovery. There is no evidence based medicine data in the
      literature about the optimal timing of decompressive surgery. A relative
      consensus exists among spine surgeons for paralysing LDH: since operative
      indication is obvious, surgery should be done as soon as possible.

PMID- 23153499
TI  - (234)U/(238)U signatures associated with uranium ore bodies: part 1 Ranger 3.
AB  - The Ranger 3 ore body is an early Proterozoic U ore body in the Alligator Rivers
      U province, Northern Territory, Australia. It has surface expression with a redox
      front located between 30 and 50 m below the surface. The ground water U
      concentration and (234)U/(238)U AR signature in the top 10 m of the weathered
      zone are reported for 357 samples collected over 4 wet seasons, at 5 depths,
      along a transect in-line with the hydraulic gradient and along the centre line of
      the ore body and its associated dispersion halo. The results show that the
      weathered zone displays a general U isotope feature for this type of ore body
      with the (234)U/(238)U AR for the ground water and amorphous phase of the solid
      matrix being less than 1. The ground water (234)U/(238)U AR is independent of the
      annual monsoonal climate and depth within the range surface to 10 m. In the
      vicinity of the U ore body the ground water (234)U/(238)U AR is 0.75 and is very
      similar to the (234)U/(238)U AR of the amorphous phase of the solid (0.76). The
      (234)U/(238)U ARs of the amorphous phase and ground water rise and separate to
      values of 0.88 and 1.02 at the end of the transect. The rise and separation in
      (234)U/(238)U AR are interpreted as evidence that the source of the U in the
      ground water is from the water-soluble sub-phase of the amorphous phase and that
      the ground water flow is too fast to allow the processes occurring across the
      solid-water interface to reach chemical equilibrium. The data set is a robust
      characterisation of the coarse and fine detail of the (234)U/(238)U AR signature
      in the weathered zone of U ore bodies.

PMID- 23153500
TI  - NR5A1 (SF-1) gene variants in a group of 26 young women with XX primary ovarian
      insufficiency.
AB  - OBJECTIVE: To determine whether NR5A1 (SF-1) variants are a cause of primary
      ovarian insufficiency (POI) in 26 young women with similar genetic background.
      DESIGN: Genetic and functional mutation study. SETTING: University hospitals.
      PATIENT(S): Genetic analysis of the NR5A1 gene in 26 XX girls with POI.
      INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): NR5A1 molecular and functional
      analysis. RESULT(S): Genetic analysis revealed a new c.763C>T (p.Arg255Cys)
      mutation and a recurrent c.437G>C (p.Gly146Ala) variant. Functional analysis of
      the p.Arg255Cys mutant showed a marked decrease in transactivation on the Cyp11a1
      and Amh promoters. The p.Gly146Ala variant was identified significantly more
      often in the patients (46.1%) than in ancestry-matched control subjects (10%).
      CONCLUSION(S): We identified one new NR5A1 mutation in a patient of our POI
      cohort (prevalence 3.8%). Moreover, although our study is limited in the number
      of cases, we report the high frequency of the p.Gly146Ala variant in this cohort
      compared with the ancestry-matched control subjects. This work highlights the
      important role of SF-1 in ovarian function.

PMID- 23153501
TI  - Review: Transport across the placenta of mice and women.
AB  - Since the advent of technologies to produce genetic knockout and transgenic mice,
      the number of mouse strains suggested to be useful as models for pregnancy
      related complications in the human has risen substantially. Some of these share
      features in common with fetal growth restriction (FGR) and preeclampsia (PE) and
      could be useful for investigating aetiologies and for testing potential
      therapeutics to improve outcome in these diseases. However, since placental
      pathology is a major underlying factor in both FGR and PE, it is important to
      understand the similarities and differences in structure and function of the
      placenta between mice and women. The main aim of this review is to directly
      compare placental exchange physiology between human and mouse. The review will
      compare human and mouse in both normal and pathological circumstances, to attempt
      to answer the question of whether placental studies in the mouse can be
      translated to the human. The review includes descriptions of placental structure
      between the species, comparisons of nutrient transport, including amino acids,
      glucose and calcium, and evidence of how these transport systems are altered in
      both human FGR and mouse models of this disease. Finally, our review will
      conclude by examining studies in which mouse models of FGR/PE have been treated
      with drugs of potential therapeutic value in women and consider whether data
      obtained in mice can be a prelude for clinical trials in human.

PMID- 23153502
TI  - The ciliary pocket.
AB  - Cilia are fascinating highly conserved organelles shared by very different
      organisms from unicellular eukaryotes to vertebrates where they are involved in
      motility and sensory functions. In vertebrates, the function of the primary
      cilium, a unique nonmotile cilium found at the surface of most cell types during
      development, remained mysterious during 40 years until its crucial function in
      the control of key signaling cascades during development and its involvement in
      complex genetic disorders now called ciliopathies were uncovered. Recent studies
      have focused on a specific membrane domain found at the base of primary cilia in
      most cell types which was already mentioned in the first descriptions of these
      cilia but did not raise much interest during 50 years. This membrane domain, the
      'ciliary pocket', also found at the base of some motile cilia, may act as a
      platform for cilia-associated vesicular trafficking and as an interface with the
      actin cytoskeleton but also likely in additional important functions which remain
      to be discovered.

PMID- 23153503
TI  - Enhanced gemcitabine-mediated cell killing of human lung adenocarcinoma by vector
      based RNA interference against PLK1.
AB  - Specific PLK1 silencing may be an effective gene therapy modality of treating
      PLK1-overexpressed cancers. In this study, we first explored the anticancer
      efficacy of three different short hairpin-expressing plasmids targeting PLK1 in
      animal model, and then determined the combination therapy effect of gemcitabine
      with PLK1-shRNA as an adjuvant. Transfection of the PLK1-shRNAs to A549 lung
      cancer cells induced significant PLK1 depletion, growth inhibition and apoptosis.
      In vivo administration of PLK1-shRNA constructs to tumor-bearing mice resulted in
      xenograft regression. Moreover, the combination of PLK1-shRNA plus low-dose
      gemcitabine (GEM) produced an additive antitumor activity on the lung tumors
      owing to an inhibition of cancer cell survival and augmented apoptosis. These
      results indicated a feasible bio-chemotherapeutic strategy for cancer.

PMID- 23153504
TI  - Towards a "Lyon molecular signature" to individualize the treatment of rectal
      cancer. Prognostic analysis of a prospective cohort of 94 rectal cancers T1-2-3
      Nx MO to be the basis of a molecular signature.
AB  - PURPOSE: In 1998 a translational research was initiated in Lyon aiming at
      identifying a prognostic "biomolecular signature" in rectal cancer. This paper
      presents the clinical outcome of the patients included in this study. PATIENTS
      AND METHODS: A total of 94 patients were included between 1998 and 2001. A
      staging with rectoscopy and biopsies was performed before treatment. In case of
      surgery, the operative specimen was analysed to evaluate the pathological
      response. There were two types of treatment: neoadjuvant radiotherapy (with or
      without concurrent chemotherapy) followed by surgery (76 cases) and radiotherapy
      alone with 'contactherapy' often associated with external beam radiotherapy (18
      patients). RESULTS: The patients had a mean age of 63years. Stage was T1: 4, T2:
      24, T3: 65 and T4: 1. The overall survival of the 94 patients was 62% at 8years
      with a rate of distant metastases of 29%. Rate of local recurrence at 8years was
      6% in the neoadjuvant group and 16% in the radiotherapy group with an overall
      8years survival in both groups respectively: 64% and 53%. There was a trend
      towards more metastases in cT3, tumour diameter above 4cm, circumferential
      extension. There was a significant increase in the risk of metastases for ypT3,
      ypN1-2 and Dworak score 1-2-3. In multivariate analysis ypT3 was significantly
      associated with a high rate of metastases (55%; P=0.0003). CONCLUSION: The rate
      of distant metastases is a major prognostic factor. These clinical results will
      serve as the base line to identify a "biomolecular signature" which could
      complement the TN(M) classification.

PMID- 23153505
TI  - Role of the investigator in phase 1 trials of anticancer drugs.

PMID- 23153506
TI  - Tolerability, safety, pharmacokinetics, and efficacy of doxorubicin-loaded anti
      EGFR immunoliposomes in advanced solid tumours: a phase 1 dose-escalation study.
AB  - BACKGROUND: Results of preclinical studies have shown that EGFR immunoliposomes
      have substantial antitumour effects. We aimed to assess the tolerability, safety,
      pharmokinetics, and efficacy of anti-EGFR immunoliposomes loaded with doxorubicin
      (anti-EGFR ILs-dox) in patients with solid tumours. METHODS: In this first-in
      man, open-label, phase 1 clinical study, we enrolled patients at University
      Hospital of Basel, Switzerland, who had EGFR-overexpressing advanced solid
      tumours no longer amenable to standard treatment. Anti-EGFR ILs-dox nanoparticles
      were constructed by covalently linking pegylated liposomes containing doxorubicin
      to antigen-binding fragments (Fab') of cetuximab. We intravenously infused the
      nanoparticle at escalating doses (doxorubicin 5 mg/m(2), 10 mg/m(2), 20 mg/m(2),
      30 mg/m(2), 40 mg/m(2), 50 mg/m(2), and 60 mg/m(2)) once every 4 weeks for a
      maximum of six cycles. The primary endpoint was to establish the maximum
      tolerated dose. We analysed patients who received at least one dose of study
      drug. This study is registered with ClinicalTrials.gov, number NCT01702129.
      FINDINGS: Between Jan 30, 2007, and March 4, 2010, we gave the drug to 29
      patients, three of whom were withdrawn from the study because we could not
      complete a safety assessment. Of the 26 patients assessed for the primary
      endpoint, two who received a dose of 60 mg/m(2) had dose-limiting toxicities (one
      had neutropenia and the other had anaemia); therefore, the maximum tolerated dose
      was defined as 50 mg/m(2). At all lower doses, anti-EGFR ILs-dox was well
      tolerated; grade 1 skin toxicity occurred in two patients only. We recorded 22
      serious adverse events (SAEs) in 17 patients, mostly due to tumour progression.
      Three SAEs were fatal. Only three SAEs (febrile neutropenia, septicaemia, and a
      fatal massive oral bleed) were probably or possibly related to study drug. No
      patients had palmar-plantar erythrodysaesthesia, alopecia, cardiotoxicity, or
      cumulative toxicity. Best response to treatment included one complete response,
      one partial response, and ten stable disease lasting 2-12 months (median 5.75
      months). INTERPRETATION: Because anti-EGFR ILs-dox was well tolerated up to 50 mg
      doxorubicin per m(2), and we recorded clinical activity, further assessment of
      this nanoparticle at this dose in phase 2 trials is warranted. FUNDING: Cancer
      League Basel, Swiss Cancer League, Schoenmakers-Muller Foundation, and Werner
      Geissberger Foundation.

PMID- 23153507
TI  - A missense mutation in the ITGA8 gene, a cell adhesion molecule gene, is
      associated with schizophrenia in Japanese female patients.
AB  - BACKGROUND: Cell adhesion molecules (CAMs) play pivotal role in the development
      of the central nervous system (CNS) and have also been reported to play role in
      the pathophysiology of schizophrenia. Missense mutations in the CAMs genes might
      alter the binding of their ligands, increasing the vulnerability to develop
      schizophrenia. METHODS: We selected 15 missense mutations in the CAMs genes of
      the CNS reported in the Kyoto Encyclopedia of Genes and Genomes (KEGG) and
      examined the association between these mutations and schizophrenia in 278
      patients and 284 control subjects (first batch). We also genotyped the positive
      single nucleotide polymorphisms (SNPs) in 567 patients and 710 control subjects
      (second batch) and in 635 patients and 639 control subjects (replication
      samples). RESULTS: Genotypic and allelic distributions of rs2298033 in the ITGA8
      gene between the schizophrenia and control groups were significantly different in
      the first batch (p=0.005 and 0.007, respectively). Gender-based analysis revealed
      that the allelic and genotypic distributions of rs2298033 in the ITGA8 were
      significantly different between the schizophrenia and control groups among
      females in both batches (p=0.010, 0.011 and 0.0086, 0.010, respectively) but not
      among males. Combine analysis of rs2298033 with the replication samples revealed
      a more significant differences (p=0.0032; 0.0035 in the overall subjects and
      p=0.0024; 0.0025 in the female subjects, respectively). The significant
      differences for rs2802808 of the NFASC gene were only observed in the female
      subgroup of the first batch. CONCLUSION: These results suggest that the ITGA8
      gene might have gender-specific roles in the development of schizophrenia.
      Further replication and functional studies are required to confirm these
      findings.

PMID- 23153508
TI  - Rac1/PAK1 signaling promotes epithelial-mesenchymal transition of podocytes in
      vitro via triggering beta-catenin transcriptional activity under high glucose
      conditions.
AB  - Ras-related C3 botulinum toxin substrate 1 (Rac1), together with its major
      downstream effector p21-activated kinase 1 (PAK1), has been identified a central
      role in cellular events such as cell cytoskeletal remodeling that contributed to
      cell migration and epithelial-mesenchymal transition (EMT). And there are data
      implicating that podocytes underwent EMT under pathological conditions. However,
      little is known about mechanisms of podocytes undergoing EMT. To address this, we
      assessed the cellular changes of podocytes after high glucose stimulation in
      vitro, detected the effects of Rac1/PAK1 signaling on podocytes in response to
      the stimuli, and investigated interactions of Rac1/PAK1 axis with beta-catenin
      and Snail under high glucose conditions. We found that in vitro high glucose
      treatment led to remarkable down-regulation of nephrin and P-cadherin, as well as
      significant up-regulation of alpha-SMA and FSP-1, suggesting that in the presence
      of high glucose, podocytes underwent EMT, during which Rac1/PAK1 signaling was
      activated. And these were notably ameliorated by Rac1 gene knockdown.
      Furthermore, beta-catenin and Snail nuclear translocation were triggered by
      Rac1/PAK1 axis, which were both markedly reversed via Rac1 gene knockdown or
      pretreatment of IPA-3, a PAK1 inhibitor. These findings elaborated that Rac1/PAK1
      signaling contributed to high glucose-induced podocyte EMT via promoting beta
      catenin and Snail transcriptional activities, which could be a potential
      mechanism involved in podocytes injury in response to stimuli under diabetic
      conditions.

PMID- 23153509
TI  - Down-regulation of NAMPT expression by miR-182 is involved in Tat-induced HIV-1
      long terminal repeat (LTR) transactivation.
AB  - Tat's transactivating activity is controlled by sirtuin 1 (SIRT1) that connects
      HIV transcription with the metabolic state of the cell. Nicotinamide
      phosphoribosyltransferase (NAMPT) is a key enzyme in the salvaging pathway for
      the synthesis of nicotinamide adenine dinucleotide (NAD(+)) that is involved in
      energy metabolism. Host encoded microRNAs (miRNAs) may influence viral
      replication. In this study, our goal was aimed to investigate the regulation of
      miR-182 in TZM-bl cells and explore the mechanisms by which miR-182 influenced
      Tat-induced HIV-1 transactivation through targeting at down-regulation of NAMPT
      expression. We showed that miR-182 was up-regulated when Tat was expressed in TZM
      bl cells. MiR-182 significantly inhibited NAMPT protein expression by acting on
      the 3'-UTR of the NAMPT mRNA. MiR-182 was involved in Tat-induced NAD(+)
      depletion, down-regulation of SIRT1 protein expression and activity, increased
      acetylation of p65. Forced expression of "miR-182 mimics" increased Tat-induced
      LTR transactivation. Our results uncover previously unknown links between Tat and
      a specific host cell miRNA that targets NAMPT. Our results suggest that
      strategies to augment NAMPT protein expression by down-regulation of miR-182 may
      have therapeutic benefits to prevent HIV-1 replication.

PMID- 23153511
TI  - Evolution of improvement and cumulative culture.
AB  - Humans have created highly developed cultures, brought about by iterative
      improvements in technology. Using a mathematical model, I investigated the
      conditions under which cultural traits tend to be improved for a higher level of
      culture to evolve. In the model, I consider three ways of learning: individual
      learning, simple social learning, and improvements of socially learned cultural
      traits (social improvement). I obtain the evolutionarily stable number of
      cultural traits acquired through each way of learning. I show that organisms
      improve many socially learned cultural traits under the following conditions: (1)
      environmental stability is intermediate; (2) the environment is severe; (3) the
      success rate of individual learning is high; (4) the utility of cultural traits
      acquired by individual learning is large; (5) the accuracy of social learning is
      high; and (6) the increase in the utility of beneficial cultural traits attained
      by social improvement is large. I also show that when organisms have greater
      ability for social improvement, the average utility of the beneficial cultural
      trait increases, the proportion of beneficial cultural traits among all cultural
      traits decreases, and the total number of cultural traits acquired by the three
      ways of learning is constant. These results shed light on the origins of human
      cumulative culture.

PMID- 23153510
TI  - Deletion of microRNA miR-223 increases Langerhans cell cross-presentation.
AB  - Langerhans cells (LCs) are skin-residential dendritic cells that regulate skin
      immunity. MicroRNAs (miRNAs) are key regulators in the control of biological
      functions in a variety of cell types. Deletion of all miRNAs interrupts the
      homeostasis and function of epidermal LCs. However, the roles of individual
      miRNAs in regulating LC development and function are still completely unknown.
      MiRNA miR-223 is especially expressed in the myeloid compartment. Here, we
      reported that miR-223 is highly expressed in freshly isolated epidermal LCs, and
      tested whether miR-223 regulates LC development and function using miR-223
      knockout (KO) mice. We found that the number, maturation, migration and
      phagocytic capacity of LCs were comparable between miR-223KO and wild-type mice.
      However, lack of miR-223 significantly increases LCs-mediated antigen-specific
      CD8(+) T cell proliferation in vivo and in vitro, while LCs from KO and WT mice
      showed comparable stimulation for antigen-specific CD4(+) T cells. Our data
      suggest that miR-223 negatively regulates LC cross-presentation, but may not be
      required for normal LC homeostasis and development.

PMID- 23153512
TI  - Proposed model for in vitro interaction between fenitrothion and DNA, by using
      competitive fluorescence, (31)P NMR, (1)H NMR, FT-IR, CD and molecular modeling.
AB  - In this work we proposed a model for in vitro interaction of fenitrothion (FEN)
      with calf thymus-DNA by combination of multispectroscopic and two dimensional
      molecular modeling (ONIOM) methods. The circular dichroism results showed that
      FEN changes the conformation of B-DNA and caused some changes to C-DNA form. The
      FT-IR results confirmed a partial intercalation between FEN and edges of all base
      pairs. The competitive fluorescence, using methylene blue as fluorescence probe,
      in the presence of increasing amounts of FEN, revealed that FEN is able to
      release the non-intercalated methylene blue from the DNA. The weak chemical shift
      and peak broadening of (1)H NMR spectrum of FEN in the presence of DNA confirmed
      a non-intercalation mode. The (31)P NMR showed that FEN interacts more with DNA
      via its -NO2 moiety. The ONIOM, based on the hybridization of QM/MM (DFT, 6.31++G
      (d,p)/UFF) methodology, was also performed by Gaussian 2003 package. The results
      revealed that the interaction is base sequence dependent, and FEN interacts more
      with AT base sequences.

PMID- 23153513
TI  - Circumcision benefits outweigh risks, but parents should choose according to
      revised AAP policy.

PMID- 23153514
TI  - Effects of natural radiation, photosynthetically active radiation and artificial
      ultraviolet radiation-B on the chloroplast organization and metabolism of
      Porphyra acanthophora var. brasiliensis (Rhodophyta, Bangiales).
AB  - We undertook a study of Porphyra acanthophora var. brasiliensis to determine its
      responses under ambient conditions, photosynthetically active radiation (PAR),
      and PAR+UVBR (ultraviolet radiation-B) treatment, focusing on changes in
      ultrastructure, and cytochemistry. Accordingly, control ambient samples were
      collected in the field, and two different treatments were performed in the
      laboratory. Plants were exposed to PAR at 60 MUmol photons m-2 s-1 and PAR + UVBR
      at 0.35 W m-2 for 3 h per day during 21 days of in vitro cultivation. Confocal
      laser scanning microscopy analysis of the vegetative cells showed single stellate
      chloroplast in ambient and PAR samples, but in PAR+UVBR-exposed plants, the
      chloroplast showed alterations in the number and form of arms. Under PAR+UVBR
      treatment, the thylakoids of the chloroplasts were disrupted, and an increase in
      the number of plastoglobuli was observed, in addition to mitochondria, which
      appeared with irregular, disrupted morphology compared to ambient and PAR
      samples. After UVBR exposure, the formation of carpospores was also observed.
      Plants under ambient conditions, as well as those treated with PAR and PAR+UVBR,
      all showed different concentrations of enzymatic response, including glutathione
      peroxidase and reductase activity. In summary, the present study demonstrates
      that P. acanthophora var. brasiliensis shows the activation of distinct
      mechanisms against natural radiation, PAR and PAR+UVBR.

PMID- 23153515
TI  - The impact of a multifaceted ergonomic intervention program on promoting
      occupational health in community nurses.
AB  - INTRODUCTION: Community nurses are exposed to high physical demands at work
      resulting in musculoskeletal disorders. The present study examined the short- and
      long-term benefits of a multifaceted intervention program designed especially for
      community nurses in Hong Kong. METHODS: Fifty community nurses working in 4 local
      hospitals participated in the study. All of them underwent an 8-week intervention
      program consisting of ergonomic training, daily exercise program, equipment
      modification, computer workstation assessment and typing training. RESULTS: All
      participants showed significant improvement in musculoskeletal symptoms and
      functional outcomes comparing pre- and post-intervention results. Significant
      reduction in symptom score was observed at 1-year follow-up compared to post
      intervention. Symptomatic group (n=40) showed more significant changes overall
      compared to asymptomatic group (n=10). CONCLUSION: Results support the positive
      benefits, both short- and long-term, of the multifaceted ergonomic intervention
      programme for community nurses.

PMID- 23153516
TI  - Identification and characterization of novel microRNA candidates from deep
      sequencing.
AB  - In our previous study, we screened a candidate new microRNA (miRNA) based on the
      deep sequencing and bioinformatics analysis. In this paper, we evaluated the
      novel miRNA in the following experiment: 1) the secondary structure of the
      precursor of novel-miR has the characteristic of a stem-loop hairpin structure,
      and mature miRNA is far from loops and bulges. 2) we used BLAST (Basic Local
      Alignment Search Tool) to compare the novel-miR sequence to that found in the
      GenBank. Novel-miR sequence existed in Mus musculus, Drosophila grimshawi, Rattus
      norvegicus, Xenopus laevis, Spodoptera frugiperda, Papio anubis, Salmo salar and
      so on. Then multiple sequence alignment (MSA) showed that sequence from 5 to 11
      bp and 13 to 17 bp exhibited 100% similarity, where there is significant sequence
      conservation. Novel-miR showed similarity in the seed region with the known miR
      3675-3p, indicating that these miRNAs are likely to belong to the same family and
      thus may share common biology. 3) novel-miR from MCF-7 and MB-MDA-231 was
      validated by Northern blot and detected in the serum and tissue samples of BC
      patients, respectively, by real-time PCR. The data showed that novel-miR was
      downregulated in the BC cancerous tissues and serum of breast cancer patients
      (P<0.05). 4) transfection of novel-miR mimics into MCF-7 cell significantly
      inhibited cell growth detected by CCK-8 assay (P<0.05). 5) to identify the mRNA
      targets of novel-miR, we performed a computational screen for genes with novel
      miR complementary sites in their 3'-UTR using several open access databases. In
      addition, we used the CapitalBio(r) Molecule Annotation System V3.0 to perform
      gene ontology (GO) analysis on the target genes of novel-miR and specific
      biological process categories were enriched. 7 genes (CUL3, KRAS, ETS1, MNT,
      CNTN3, CCNK and FOXO3) which have a high prediction score and are associated with
      cell proliferation, apoptosis and cell cycle were chosen. 3'-UTR luciferase
      report assay suggested that miR-BS1 negatively regulated CNTN3. In the
      conclusion, novel-miR, named miR-3675b, is a true, functional and novel miRNA.
      Candidate novel miRNA from deep sequencing which will be qualified as a "real"
      miRNA must be validated by a series of functional experiments.

PMID- 23153517
TI  - Medicinal property, phytochemistry and pharmacology of several Jatropha species
      (Euphorbiaceae): a review.
AB  - The genus Jatropha (Euphorbiaceae) comprises of about 170 species of woody trees,
      shrubs, subshrubs or herbs in the seasonally dry tropics of the Old and the New
      World. They are used in medicinal folklore to cure various diseases of 80% of the
      human population in Africa, Asia and Latin America. Species from this genus have
      been popular to cure stomachache, toothache, swelling, inflammation, leprosy,
      dysentery, dyscrasia, vertigo, anemia, diabetis, as well as to treat HIV and
      tumor, opthalmia, ringworm, ulcers, malaria, skin diseases, bronchitis, asthma
      and as an aphrodisiac. They are also employed as ornamental plants and energy
      crops. Cyclic peptides alkaloids, diterpenes and miscellaneous compounds have
      been reported from this genus. Extracts and pure compounds of plants from this
      genus are reported for cytotoxicity, tumor-promoting, antimicrobial,
      antiprotozoal, anticoagulant, immunomodulating, anti-inflammatory, antioxidant,
      protoscolicidal, insecticidal, molluscicidal, inhibition AChE and toxicity
      activities.

PMID- 23153518
TI  - Tetracyclic triterpenoids and terpenylated coumarins from the bark of Ailanthus
      altissima ("Tree of Heaven").
AB  - Tetracyclic triterpenoids (named as altissimanins A-E, 1-5) and a terpenylated
      coumarin (denominated as altissimacoumarin G, 6), along with fifteen known
      compounds (7-21) were isolated from the bark of Ailanthus altissima. Structures
      of compounds 1-6 were established by spectroscopic methods and chemical
      transformations. Altissimanin A (1) is a tirucallane-type triterpenoid bearing an
      uncommon oxetane ring in the side-chain, while altissimanins D (4) and E (5) are
      two unprecedented dimers each consisting of one tirucallane-type and one
      dammarane-type triterpenoid moiety. All the isolates were evaluated for their
      cytotoxic effects against a small panel of human cancer cell lines.

PMID- 23153519
TI  - Immediate breast reconstruction using porcine acellular dermal matrix
      (StratticeTM): long-term outcomes and complications.
AB  - BACKGROUND: There has been limited reported experience with the use of
      StratticeTM (LifeCell Corp., Branchburg, NJ), a porcine-derived acellular dermal
      matrix, in implant-based breast reconstruction. The purpose of this study is to
      evaluate our experience with this matrix. METHODS: Patients who underwent
      immediate single-stage or two-stage implant-based breast reconstruction with the
      assistance of Strattice were included in this study. Patient charts were reviewed
      for indications for mastectomy, adjunctive radiotherapy use, implant or expander
      volume, length of follow-up period, and type and incidence of complications
      during the follow-up period. Biopsies of Strattice were taken for histological
      analyses. RESULTS: A total of 105 reconstructions were performed in 54 patients:
      77% were prophylactic and 23% were oncologic. All, but 4, reconstructions were
      single stage. Mean implant volume of single-stage reconstructions were 444.1
      (range: 150-700 cc) and mean expander volume after completion of expansion was
      400 (range: 350-450). Mean follow-up period was 41.3 months (range: 35.5-48.4
      months). Total complication rate was 8.6%. Complications occurred in 9 breasts:
      implant loss or explantation (3.8%), infection (3.8%), skin breakdown or necrosis
      (2.9%), seroma (1.9%), implant exposure (1.0%), and delayed skin healing (1.0%).
      Histological analyses of implanted Strattice revealed a viable matrix with
      fibroblast infiltration and revascularization. CONCLUSIONS: Over a mean 3.5-year
      follow-up period, low complication rates and good outcomes were observed with the
      use of Strattice that are comparable to those reported with human acellular
      dermal matrices.

PMID- 23153520
TI  - Correcting radial shift in fractures of the distal radius.

PMID- 23153521
TI  - What is the nature of serotonergic abnormalities in human aggression?

PMID- 23153522
TI  - Adhesion of Fusobacterium necrophorum to bovine endothelial cells is mediated by
      outer membrane proteins.
AB  - Fusobacterium necrophorum, a Gram-negative anaerobe, is frequently associated
      with suppurative and necrotic infections of animals and humans. The organism is a
      major bovine pathogen, and in cattle, the common fusobacterial infections are
      hepatic abscesses, foot rot, and necrotic laryngitis. The species comprises two
      subspecies: F. necrophorum subsp. necrophorum and F. necrophorum subsp.
      funduliforme. Bacterial adhesion to the host cell surface is a critical initial
      step in the pathogenesis, and outer membrane proteins (OMP) play an important
      role in adhesion and establishment of certain Gram-negative bacterial infections.
      The means by which F. necrophorum attaches to epithelial or endothelial cells has
      not been determined. We evaluated whether OMP of F. necrophorum, isolated from a
      liver abscess, mediated adhesion to bovine endothelial cells (adrenal gland
      capillary endothelial cell line). The extent of binding of subsp. necrophorum to
      the endothelial cells was higher than that of F. necrophorum subsp. funduliforme.
      Trypsin treatment of bacterial cells decreased their binding to endothelial cells
      indicating the protein nature of adhesins. Preincubation of endothelial cells
      with OMP extracted from F. necrophorum decreased the binding of bacterial cells.
      In addition, binding of each subspecies to endothelial cells was inhibited by
      polyclonal antibodies raised against respective OMP and the antibody-mediated
      inhibition was subspecies specific. The western blot analysis of OMP bound to
      endothelial cells with anti-OMP antibodies showed four OMP of 17, 24, 40 and 74
      kDa. We conclude that OMP of F. necrophorum play a role in adhesion of bacterial
      cells to the endothelial cells.

PMID- 23153523
TI  - [Medical specialty choice: what impact of teaching? Results of a survey of two
      medical schools].
AB  - BACKGROUND: Determinants of career choice are numerous. The impact of teaching
      has not yet been reported. OBJECTIVES: The objectives were to assess determinants
      of career choice among DCEM 4 (sixth year) medical students at Paris Descartes
      University and Pierre-et-Marie-Curie University; and to determine the impact of
      teaching on career choice. MATERIALS AND METHODS: Prospective study based on an
      online survey, after the 2011 National Grading Examination, among 865 DCEM 4
      students. Collection of socio-demographic data, commonly reported determinants of
      medical specialty choice, and the impact of the teaching on this choice. RESULTS:
      Two hundred and seven (24%) students (67% female) answered the survey. During
      their medical studies, students changed their mind on their career choice an
      average of 3 times (range 0-10). Nearly 60% of them made their final choice
      during the fifth year. Choices varied significantly between the beginning and end
      of the studies (P<0.0001), with interest in surgical and pediatric careers
      falling significantly (P<0.0001 and p=0.0003 respectively). At the time of
      expressing the final choice, surgical careers were mainly chosen by male students
      (19.8% of males vs. 9.9% of females, P=0.04), whereas medical careers were chosen
      equally by males and females (37.7% vs. 35.5%, P=0.75). The main determinant was
      interest in the specialty (96% of students), followed by perceived quality of
      life (56% of students). Teaching was a determinant for 74% of students, of whom
      88% were influenced by the teaching they received during their clinical training.
      In 42% of cases, the teacher did not belong to the university corpus. In 10% of
      cases, students were discouraged from their choice by a teacher (a university
      professor in 50%). DISCUSSION AND CONCLUSION: Our results highlight the impact of
      both teaching and the teacher on medical students' career choice. If career
      choice is now compelled in France by the "careers law", teaching is more than
      ever an effective way of interesting students in specialties which might appear
      less attractive. At a time when the selection of candidates for hospital
      university careers is mainly based on publications, this study calls for
      reflection on the evaluation of these candidates' teaching qualities.

PMID- 23153524
TI  - Alisertib (MLN8237) an investigational agent suppresses Aurora A and B activity,
      inhibits proliferation, promotes endo-reduplication and induces apoptosis in T
      NHL cell lines supporting its importance in PTCL treatment.
AB  - Peripheral T-cell lymphomas (PTCL) are a diverse group of rare non-Hodgkin
      lymphomas (NHL) that carry a poor prognosis and are in need of effective
      therapies. Alisertib (MLN8237) an investigational agent that inhibits Aurora A
      Ser/Thr kinase has shown activity in PTCL patients. Here we demonstrate that
      aurora A and B are highly expressed in T-cell lymphoma cell lines. In PTCL
      patient samples aurora A was positive in 3 of 24 samples and co-expressed with
      aurora B. Aurora B was positive in tumor cells in 22 of 32 samples. Of the
      subtypes of PTCL, aurora B was over-expressed in PTCL (NOS) [73%], T-NHL [100%],
      ALCL (Alk-Neg) [100%] and AITL [100%]. Treatment with MLN8237 inhibited PTCL cell
      proliferation in CRL-2396 and TIB-48 cells with an IC50 of 80-100nM. MLN8237
      induced endo-reduplication in a dose and time dependent manner in PTCL cell lines
      leading to apoptosis demonstrated by flow cytometry and PARP-cleavage at
      concentrations achieved in early phase clinical trials. Moreover, inhibition of
      HisH3 and aurora A phosphorylation was dose dependent and strongly correlated
      with endo-reduplication. The data provide a sound rationale for aurora inhibition
      in PTCL as a therapeutic modality and warrants clinical trial evaluation.

PMID- 23153525
TI  - Localization of the NRAS:BCL-2 complex determines anti-apoptotic features
      associated with progressive disease in myelodysplastic syndromes.
AB  - We have previously demonstrated that two prognostic features of myelodysplastic
      syndromes (MDS) and acute myelogenous leukemia (AML), mutant NRAS and over
      expressing BCL-2, cooperate physically and functionally in vivo. Screening of MDS
      patient bone marrow (BM) identified NRAS:BCL-2 co-localization in 64% cases,
      correlating with percentage BM blasts, apoptotic features and disease status
      (p<0.0001). Localization of the complex at the plasma membrane or the
      mitochondria correlated with disease and apoptosis features in MDS patients,
      whilst caspase-9 mediated mechanism was elucidated in vivo and in vitro. The
      intensity and localization of the RAS:BCL-2 complex merits further evaluation as
      a novel biomarker of MDS.

PMID- 23153526
TI  - Bone marrow dendritic cells are reduced in patients with high-risk
      myelodysplastic syndromes.
AB  - Dendritic cells (DC) are antigen-presenting cells that play a pivotal role in
      coordinating functions of the immune system. Previous studies suggest that bone
      marrow (BM) failure in myelodysplastic syndromes (MDS) may be in part immune
      mediated, and that the high propensity for relapse may reflect decreased immune
      surveillance. This study aimed to assess the frequency of DC in BM samples from
      well-annotated untreated MDS patients by using 4-colour flow cytometry. DC levels
      were markedly reduced in all subtypes of MDS. The clinical impact of this finding
      on therapy response and relapse after, e.g. allogeneic stem cell transplantation
      warrants further investigation.

PMID- 23153528
TI  - Metastatic ability: adapting to a tissue site unseen.
AB  - The microenvironment of the primary as well as the metastatic tumor sites can
      determine the ability for a disseminated tumor to progress. In this issue of
      Cancer Cell, Calon and colleagues find that systemic TGF-beta can facilitate
      colon cancer metastatic engraftment and expansion.

PMID- 23153527
TI  - Association of retinol binding protein 4 with risk of gestational diabetes.
AB  - AIM: We investigated association of maternal retinol binding protein 4 (RBP4)
      with risk of gestational diabetes (GDM). METHODS: GDM cases (N=173) and controls
      (N=187) were selected from among participants of a cohort study of risk factors
      of pregnancy complications. Early pregnancy (16 weeks on average) serum RBP4
      concentration was measured using an ELISA-based immunoassay. Logistic regression
      was used to estimate unadjusted and adjusted odds ratios (ORs/aORs) and 95%
      confidence intervals (95%CI). RESULTS: Mean serum RBP4 was significantly higher
      among GDM cases compared with controls (47.1 vs. 41.1 MUg/ml, respectively; p
      value <0.05). Participants in the highest quartile for serum RBP4 had a 1.89-fold
      higher risk of GDM compared with participants in the lowest quartile (95%CI: 1.05
      3.43). However, this relationship did not reach statistical significance after
      adjustment for confounders (aOR: 1.54; 95%CI: 0.82-2.90). Women who were >=35
      years old and who had high RBP4 (>=38.3 MUg/ml, the median) had a 2.31-fold
      higher risk of GDM compared with women who were <35 years old and had low RBP4
      (<38.3 MUg/ml) (aOR: 2.31; 95%CI: 1.26-4.23; p-value for interaction=0.021).
      CONCLUSION: Overall, there is modest evidence of a positive association of early
      pregnancy elevated RBP4 concentration with increased GDM risk, particularly among
      women with advanced age.

PMID- 23153529
TI  - PGAMgnam style: a glycolytic switch controls biosynthesis.
AB  - Therapeutic strategies that target glycolysis and biosynthetic pathways in cancer
      cells are currently the main focus of research in the field of cancer metabolism.
      In this issue of Cancer Cell, Hitosugi and colleagues show that targeting PGAM1
      could be a way of "killing two birds with one stone".

PMID- 23153530
TI  - BMP meets AML: induction of BMP signaling by a novel fusion gene promotes
      pediatric acute leukemia.
AB  - In this issue of Cancer Cell, Gruber et al. report that a significant proportion
      of children with acute megakaryoblastic leukemia acquire a translocation that
      confers enhanced BMP signaling and promotes self-renewal of hematopoietic
      progenitors. This study presents novel therapeutic targets that may lead to
      improved therapies for this aggressive leukemia.

PMID- 23153531
TI  - Epigenetic therapy leaps ahead with specific targeting of EZH2.
AB  - The Polycomb epigenetic silencing protein EZH2 is affected by gain-of-function
      somatic mutations in B cell lymphomas. Two recent reports describe the
      development of highly selective EZH2 inhibitors and reveal mutant EZH2 as playing
      an essential role in maintaining lymphoma proliferation. EZH2 inhibitors are thus
      a promising new targeted therapy for lymphoma.

PMID- 23153532
TI  - Dependency of colorectal cancer on a TGF-beta-driven program in stromal cells for
      metastasis initiation.
AB  - A large proportion of colorectal cancers (CRCs) display mutational inactivation
      of the TGF-beta pathway, yet, paradoxically, they are characterized by elevated
      TGF-beta production. Here, we unveil a prometastatic program induced by TGF-beta
      in the microenvironment that associates with a high risk of CRC relapse upon
      treatment. The activity of TGF-beta on stromal cells increases the efficiency of
      organ colonization by CRC cells, whereas mice treated with a pharmacological
      inhibitor of TGFBR1 are resilient to metastasis formation. Secretion of IL11 by
      TGF-beta-stimulated cancer-associated fibroblasts (CAFs) triggers GP130/STAT3
      signaling in tumor cells. This crosstalk confers a survival advantage to
      metastatic cells. The dependency on the TGF-beta stromal program for metastasis
      initiation could be exploited to improve the diagnosis and treatment of CRC.

PMID- 23153533
TI  - Phosphoglycerate mutase 1 coordinates glycolysis and biosynthesis to promote
      tumor growth.
AB  - It is unclear how cancer cells coordinate glycolysis and biosynthesis to support
      rapidly growing tumors. We found that the glycolytic enzyme phosphoglycerate
      mutase 1 (PGAM1), commonly upregulated in human cancers due to loss of TP53,
      contributes to biosynthesis regulation in part by controlling intracellular
      levels of its substrate, 3-phosphoglycerate (3-PG), and product, 2
      phosphoglycerate (2-PG). 3-PG binds to and inhibits 6-phosphogluconate
      dehydrogenase in the oxidative pentose phosphate pathway (PPP), while 2-PG
      activates 3-phosphoglycerate dehydrogenase to provide feedback control of 3-PG
      levels. Inhibition of PGAM1 by shRNA or a small molecule inhibitor PGMI-004A
      results in increased 3-PG and decreased 2-PG levels in cancer cells, leading to
      significantly decreased glycolysis, PPP flux and biosynthesis, as well as
      attenuated cell proliferation and tumor growth.

PMID- 23153534
TI  - Loss of the Par3 polarity protein promotes breast tumorigenesis and metastasis.
AB  - Loss of epithelial organization is a hallmark of carcinomas, but whether polarity
      regulates tumor growth and metastasis is poorly understood. To address this
      issue, we depleted the Par3 polarity gene by RNAi in combination with oncogenic
      Notch or Ras(61L) expression in the murine mammary gland. Par3 silencing
      dramatically reduced tumor latency in both models and produced invasive and
      metastatic tumors that retained epithelial marker expression. Par3 depletion was
      associated with induction of MMP9, destruction of the extracellular matrix, and
      invasion, all mediated by atypical PKC-dependant JAK/Stat3 activation.
      Importantly, Par3 expression is significantly reduced in human breast cancers,
      which correlates with active aPKC and Stat3. These data identify Par3 as a
      regulator of signaling pathways relevant to invasive breast cancer.

PMID- 23153535
TI  - Differential remodeling of actin cytoskeleton architecture by profilin isoforms
      leads to distinct effects on cell migration and invasion.
AB  - Dynamic actin cytoskeletal reorganization is integral to cell motility. Profilins
      are well-characterized regulators of actin polymerization; however, functional
      differences among coexpressed profilin isoforms are not well defined. Here, we
      demonstrate that profilin-1 and profilin-2 differentially regulate membrane
      protrusion, motility, and invasion; these processes are promoted by profilin-1
      and suppressed by profilin-2. Compared to profilin-1, profilin-2 preferentially
      drives actin polymerization by the Ena/VASP protein, EVL. Profilin-2 and EVL
      suppress protrusive activity and cell motility by an actomyosin contractility
      dependent mechanism. Importantly, EVL or profilin-2 downregulation enhances
      invasion in vitro and in vivo. In human breast cancer, lower EVL expression
      correlates with high invasiveness and poor patient outcome. We propose that
      profilin-2/EVL-mediated actin polymerization enhances actin bundling and
      suppresses breast cancer cell invasion.

PMID- 23153536
TI  - ATF4 regulates MYC-mediated neuroblastoma cell death upon glutamine deprivation.
AB  - Oncogenic Myc alters mitochondrial metabolism, making it dependent on exogenous
      glutamine (Gln) for cell survival. Accordingly, Gln deprivation selectively
      induces apoptosis in MYC-overexpressing cells via unknown mechanisms. Using MYCN
      amplified neuroblastoma as a model, we identify PUMA, NOXA, and TRB3 as executors
      of Gln-starved cells. Gln depletion in MYC-transformed cells induces apoptosis
      through ATF4-dependent, but p53-independent, PUMA and NOXA induction. MYC
      transformed cells depend on both glutamate-oxaloacetate transaminase and
      glutamate dehydrogenase to maintain Gln homeostasis and suppress apoptosis.
      Consequently, either ATF4 agonists or glutaminolysis inhibitors potently induce
      apoptosis in vitro and inhibit tumor growth in vivo. These results reveal
      mechanisms whereby Myc sensitizes cells to apoptosis, and validate ATF4 agonists
      and inhibitors of Gln metabolism as potential Myc-selective cancer therapeutics.

PMID- 23153537
TI  - Aberrant overexpression of IL-15 initiates large granular lymphocyte leukemia
      through chromosomal instability and DNA hypermethylation.
AB  - How inflammation causes cancer is unclear. Interleukin-15 (IL-15) is a pro
      inflammatory cytokine elevated in human large granular lymphocyte (LGL) leukemia.
      Mice overexpressing IL-15 develop LGL leukemia. Here, we show that prolonged in
      vitro exposure of wild-type (WT) LGL to IL-15 results in Myc-mediated
      upregulation of aurora kinases, centrosome aberrancies, and aneuploidy.
      Simultaneously, IL-15 represses miR-29b via induction of Myc/NF-kappaBp65/Hdac-1,
      resulting in Dnmt3b overexpression and DNA hypermethylation. All this is
      validated in human LGL leukemia. Adoptive transfer of WT LGL cultured with IL-15
      led to malignant transformation in vivo. Drug targeting that reverses miR-29b
      repression cures otherwise fatal LGL leukemia. We show how excessive IL-15
      initiates cancer and demonstrate effective drug targeting for potential therapy
      of human LGL leukemia.

PMID- 23153538
TI  - Crosstalk between ROR1 and the Pre-B cell receptor promotes survival of t(1;19)
      acute lymphoblastic leukemia.
AB  - We report that t(1;19) ALL cells universally exhibit expression of and dependence
      on the cell surface receptor ROR1. We further identify t(1;19) ALL cell
      sensitivity to the kinase inhibitor dasatinib due to its inhibition of the pre-B
      cell receptor (pre-BCR) signaling complex. These phenotypes are a consequence of
      developmental arrest at an intermediate/late stage of B-lineage maturation.
      Additionally, inhibition of pre-BCR signaling induces further ROR1 upregulation,
      and we identify distinct ROR1 and pre-BCR downstream signaling pathways that are
      modulated in a counterbalancing manner-both leading to AKT phosphorylation.
      Consistent with this, AKT phosphorylation is transiently eliminated after
      dasatinib treatment, but is partially restored following dasatinib potentiation
      of ROR1 expression. Consequently, ROR1 silencing accentuates dasatinib killing of
      t(1;19) ALL cells.

PMID- 23153541
TI  - SnapShot: Acute myeloid leukemia.

PMID- 23153539
TI  - Relief of profound feedback inhibition of mitogenic signaling by RAF inhibitors
      attenuates their activity in BRAFV600E melanomas.
AB  - BRAF(V600E) drives tumors by dysregulating ERK signaling. In these tumors, we
      show that high levels of ERK-dependent negative feedback potently suppress ligand
      dependent mitogenic signaling and Ras function. BRAF(V600E) activation is Ras
      independent and it signals as a RAF-inhibitor-sensitive monomer. RAF inhibitors
      potently inhibit RAF monomers and ERK signaling, causing relief of ERK-dependent
      feedback, reactivation of ligand-dependent signal transduction, increased Ras
      GTP, and generation of RAF-inhibitor-resistant RAF dimers. This results in a
      rebound in ERK activity and culminates in a new steady state, wherein ERK
      signaling is elevated compared to its initial nadir after RAF inhibition. In this
      state, ERK signaling is RAF inhibitor resistant, and MEK inhibitor sensitive, and
      combined inhibition results in enhancement of ERK pathway inhibition and
      antitumor activity.

PMID- 23153542
TI  - Intrauterine stress and male cohort quality: the case of September 11, 2001.
AB  - Empirical research and the theory of natural selection assert that male mortality
      more than female mortality responds to ambient stressors in utero. Although
      population stressors may adversely damage males that survive to birth, the rival
      culled cohort hypothesis contends that males born during stressful times may
      exhibit better health than males in other cohorts because fetal loss has "culled"
      the frailest males. We tested these hypotheses by examining child developmental
      outcomes in a U.S. birth cohort reportedly affected in utero by the September 11,
      2001 attacks. We used as outcomes the Bayley cognitive score and child height-for
      age from the Early Childhood Longitudinal Study-Birth Cohort. Previous research
      demonstrates a male-specific effect of 9/11 on California infants born in
      December 2001. We, therefore, compared cognition and height of this cohort with
      males born prior to the 9/11 attacks. We controlled for unobserved confounding
      across gender, season, and region by using triple-difference regression models (N
      = 6950). At 24 months, California males born in December scored greater than
      expected in cognitive ability (coef = 9.55, standard error = 3.37; p = 0.004). We
      observed no relation with height. Results remained robust to alternative
      specifications. Findings offer partial support for the culled cohort hypothesis
      in that we observed greater than expected cognitive scores at two years of age
      among a cohort of males affected by 9/11 in utero. Contemporary population
      stressors may induce male-specific culling, thereby resulting in relatively
      improved development among males that survive to birth.

PMID- 23153543
TI  - Including quality attributes in efficiency measures consistent with net benefit:
      creating incentives for evidence based medicine in practice.
AB  - Evidence based medicine supports net benefit maximising therapies and strategies
      in processes of health technology assessment (HTA) for reimbursement and subsidy
      decisions internationally. However, translation of evidence based medicine to
      practice is impeded by efficiency measures such as cost per case-mix adjusted
      separation in hospitals, which ignore health effects of care. In this paper we
      identify a correspondence method that allows quality variables under control of
      providers to be incorporated in efficiency measures consistent with maximising
      net benefit. Including effects framed from a disutility bearing (utility
      reducing) perspective (e.g. mortality, morbidity or reduction in life years) as
      inputs and minimising quality inclusive costs on the cost-disutility plane is
      shown to enable efficiency measures consistent with maximising net benefit under
      a one to one correspondence. The method combines advantages of radial properties
      with an appropriate objective of maximising net benefit to overcome problems of
      inappropriate objectives implicit with alternative methods, whether specifying
      quality variables with utility bearing output (e.g. survival, reduction in
      morbidity or life years), hyperbolic or exogenous variables. This correspondence
      approach is illustrated in undertaking efficiency comparison at a clinical
      activity level for 45 Australian hospitals allowing for their costs and mortality
      rates per admission. Explicit coverage and comparability conditions of the
      underlying correspondence method are also shown to provide a robust framework for
      preventing cost-shifting and cream-skimming incentives, with appropriate
      qualification of analysis and support for data linkage and risk adjustment where
      these conditions are not satisfied. Comparison on the cost-disutility plane has
      previously been shown to have distinct advantages in comparing multiple
      strategies in HTA, which this paper naturally extends to a robust method and
      framework for comparing efficiency of health care providers in practice.
      Consequently, the proposed approach provides a missing link between HTA and
      practice, to allow active incentives for evidence based net benefit maximisation
      in practice.

PMID- 23153540
TI  - An Inv(16)(p13.3q24.3)-encoded CBFA2T3-GLIS2 fusion protein defines an aggressive
      subtype of pediatric acute megakaryoblastic leukemia.
AB  - To define the mutation spectrum in non-Down syndrome acute megakaryoblastic
      leukemia (non-DS-AMKL), we performed transcriptome sequencing on diagnostic
      blasts from 14 pediatric patients and validated our findings in a
      recurrency/validation cohort consisting of 34 pediatric and 28 adult AMKL
      samples. Our analysis identified a cryptic chromosome 16 inversion
      (inv(16)(p13.3q24.3)) in 27% of pediatric cases, which encodes a CBFA2T3-GLIS2
      fusion protein. Expression of CBFA2T3-GLIS2 in Drosophila and murine
      hematopoietic cells induced bone morphogenic protein (BMP) signaling and resulted
      in a marked increase in the self-renewal capacity of hematopoietic progenitors.
      These data suggest that expression of CBFA2T3-GLIS2 directly contributes to
      leukemogenesis.

PMID- 23153544
TI  - The re-construction of women's sexual lives after pelvic radiotherapy: a critique
      of social constructionist and biomedical perspectives on the study of female
      sexuality after cancer treatment.
AB  - Pelvic radiotherapy creates physical effects and psychological responses that
      negatively affect the sexual health of women and couples, yet these sexual
      consequences are not frequently researched or clinically assessed. This focused
      ethnographic study explored factors that influence the clinical assessment of
      treatment-induced female sexual difficulties after pelvic radiotherapy within
      routine medical follow-up. Participant observation of follow-up clinics (n = 69)
      and in-depth interviews with 24 women, 5 partners and 20 health professionals
      were undertaken at two cancer centres in the South East of England from 2005 to
      2006. Thematic analysis of interview transcripts resulted in five emergent
      themes, two of which are explored in detail within this paper. A social
      constructionist approach to human sexuality was used to explore representations
      of female sexuality in oncology follow-up constructed by clinicians, women and
      their partners. Yet neither social constructionist nor biomedical (the
      predominant model in medical follow-up) perspectives on human sexuality provided
      an adequate interpretation of these study findings. This paper argues that the
      comprehensive study and practice of sexual rehabilitation in oncology requires a
      synthesis of both biomedical and social constructionist perspectives in order to
      capture the complex, subjective and embodied nature of the female sexual response
      in both health and illness.

PMID- 23153545
TI  - Sonodynamic and sonocatalytic damage of BSA molecules by Cresol Red, Cresol Red
      DA and Cresol Red-DA-Fe under ultrasonic irradiation.
AB  - The interaction of Cresol Red derivatives (Cresol Red (o-Cresolsulfonphthalein),
      Cresol Red-DA (3,3'-Bis [N,N-di (carboxymethyl) aminomethyl]-o
      cresolsulfonphthalein) and Cresol Red-DA-Fe(III) (3,3'-Bis [N,N-di
      (carboxymethyl) aminomethyl]-o-cresolsulfonphthalein-Ferrous(III)) with bovine
      serum albumin (BSA) were studied by the combination of ultraviolet spectroscopy,
      circular dichroism (CD) spectroscopy, fluorescence spectroscopy and synchronous
      fluorescence spectroscopy. On that basis, the sonodynamic and sonocatalytic
      damages of Cresol Red derivatives to BSA under ultrasonic irradiation were also
      investigated by means of corresponding spectrum technology. Meanwhile, some
      influenced factors such as ultrasonic irradiation time, Cresol Red derivatives
      concentration and ionic strength on the damage degree of BSA molecules were also
      reviewed. In addition, the binding site and damage site of BSA molecules were
      estimated by synchronous fluorescence spectra. Finally, the results of oxidation
      extraction photometry (OEP) using several reactive oxygen species (ROS)
      scavengers indicated that the damage of BSA molecules is mainly due to the
      generation of ROS. Perhaps, this paper may offer some important subjects for
      broadening the application of Cresol Red derivatives in sonodynamic therapy (SDT)
      and sonocatalytic therapy (SCT) technologies for tumor treatment.

PMID- 23153546
TI  - Changes in male hormone profile after occupational organophosphate exposure. A
      longitudinal study.
AB  - There is a growing concern about the endocrine effects of long-term, low-level
      exposure to organophosphate (OP) compounds. Studies on experimental animals have
      found that OP pesticides have an impact on the endocrine system and a few
      clinical and epidemiological studies have also shown that OPs may affect the male
      hormone profile, although results are inconsistent. We have evaluated the effect
      of exposure to OP pesticides, measured through urinary levels of six
      dialkylphosphate (DAP) metabolites, on male hormone profile in 136 floriculture
      workers from the State of Mexico and Morelos during two agricultural periods with
      different degree of pesticide exposure. Generalized estimated equations (GEE)
      models were developed and adjusted for several potential confounders, including
      PON1 enzyme activity, as a biomarker of susceptibility, and serum levels of p,p'
      DDE, a metabolite of the pesticide DDT widely used in Mexico until 1999 for
      control of agricultural pests and malaria. Exposure of male floriculture workers
      to OP pesticides was associated with increased serum levels of follicle
      stimulating hormone (FSH) and prolactin and with decreased serum testosterone and
      inhibin B levels. Among all DAPs tested, only DETP was inversely associated with
      luteinizing hormone (LH). Estradiol showed a marginally significant positive
      trend with DEP and DETP derivatives. In conclusion, OP pesticides may have an
      impact on the endocrine function because of their potential to modify the male
      hormone profile as a function of the type of pesticide used as well as the
      magnitude of exposure.

PMID- 23153547
TI  - New developments in the pharmacological modulation of wound healing after
      glaucoma filtration surgery.
AB  - Despite the advent of many new devices for glaucoma surgery, scarring is the main
      cause of suboptimal pressure control and surgical failure in all forms of
      surgery. The cytotoxic antimetabolites, 5-flurouracil and mitomycin C both
      prolong success but with the increased risk of blinding complications. A greater
      understanding of the cellular mechanisms of the wound healing response has led to
      the identification and modulation of potential therapeutic targets. These include
      transforming factor beta, inflammatory mediators, the acute phase protein serum
      amyloid P, vascular endothelial growth factor and the matrix metallaproteinases.
      While optimal drug delivery is still a major challenge, modulating these effects
      either directly or through downstream signalling promises to yield anti-scarring
      efficacy, while minimising side effects.

PMID- 23153548
TI  - Beneficial remodeling of small saccular intracranial aneurysms after staged stent
      only treatment: a case series.
AB  - BACKGROUND: We evaluated the effect of stent alone treatment for small
      intracranial aneurysms that were not amenable to coil embolization without prior
      stent reconstruction. METHODS: This case series was conducted in the
      neurosurgical service at a tertiary care hospital in Denver, Colorado. Nine
      patients were electively treated for intracranial aneurysms. All patients had a
      single low porosity stent reconstruction device placed across the neck of a small
      intracranial aneurysm. The main outcome measures were changes in aneurysm size
      and parent vessel morphology during follow-up. RESULTS: Nine patients underwent
      stent alone treatment for unruptured intracranial aneurysms. The mean follow-up
      period was 9.6 months (range 6-17 months). There were no cases of periprocedural
      morbidity or aneurysm rupture during follow-up. All aneurysms decreased in size,
      and 3 of 9 aneurysms were gone at follow-up. In addition, at follow-up all parent
      vessels demonstrated straightening about the aneurysm site. CONCLUSIONS:
      Beneficial remodeling with a decrease in the size of small intracranial aneurysms
      may be seen after treatment with a single stent alone, particularly if the
      aneurysm arises at an arterial bend or bifurcation. This phenomenon may be
      related to a degree of straightening of the parent artery, improving hemodynamic
      conditions about the aneurysm site.

PMID- 23153549
TI  - Penumbral imaging by using perfusion computed tomography and perfusion-weighted
      magnetic resonance imaging: current concepts.
AB  - Perfusion computed tomography and perfusion-weighted magnetic resonance imaging
      are used to evaluate the extent of the area with ischemic penumbra; however,
      different parameters, algorithms, and software packages show significant
      discrepancies in the size of perfusion abnormalities, which should be minimized.
      Recently, cross-validation studies were performed using digital phantoms and have
      elucidated the precision and reliability of various penumbral imaging techniques.
      These research initiatives can promote further multicenter trials on
      recanalization therapies by providing accurate inclusion/exclusion criteria for
      appropriate patient selection. 

PMID- 23153550
TI  - Association of physical activity with the visuospatial/executive functions of the
      montreal cognitive assessment in patients with vascular cognitive impairment.
AB  - BACKGROUND: The Montreal Cognitive Assessment (MoCA) is more suitable than the
      Mini-Mental State Examination (MMSE) for the detection of vascular cognitive
      impairment. In this study, we performed a correlation analysis of MoCA/MMSE
      scores with daily physical activity in patients with subcortical ischemic white
      matter changes. METHODS: Ten patients (average 75.9 +/- 9.1 years old) with
      extensive leukoaraiosis detected on magnetic resonance imaging underwent
      cognitive testing, including the MMSE and the Japanese version of the MoCA (MoCA
      J). Physical activity was monitored with the Kenz Lifecorder EX device (Suzuken,
      Nagoya, Japan) to assess daily physical activity in terms of caloric expenditure,
      motor activity, number of steps, and walking distance for 6 months. Correlations
      of individual physical activity with total and subscale scores of MMSE/MoCA-J or
      6-month interval change of MoCA-J scores were assessed. RESULTS: The total or
      subscale scores of the MMSE did not correlate with any parameters of physical
      activity. However, the mean number of steps and walking distance significantly
      correlated with the total MoCA-J scores (r = .67 and .64, respectively) and its
      visuospatial/executive subscores (r = .66 and .66, respectively). The mean
      interval change of MoCA-J was + .6; those who improved number of steps (n = 4;
      80.5 +/- 3.0 years of age) had significantly preserved MoCA-J scores compared to
      those who did not (n = 6; 73.0 +/- 11.6 years of age; +2.0 versus - .3; P =
      .016). CONCLUSIONS: These results suggest that MoCA is useful to detect a
      biologically determined specific relationship between physical activity and
      executive function. In addition, physical exercise, such as walking, may help
      enhance cognitive function in patients with vascular cognitive impairment of
      subcortical origin.

PMID- 23153551
TI  - The role of small vessel disease in re-exacerbation of stroke symptoms within 24
      hours after tissue plasminogen activator infusion.
AB  - BACKGROUND: The purpose of this study was to examine the frequency and
      characteristics of re-exacerbation of stroke symptoms within 24 hours after
      tissue plasminogen activator (t-PA) infusion. METHODS: We studied consecutive
      stroke patients treated with t-PA within 3 hours of onset of symptoms admitted
      between October 2005 and March 2010. We divided patients into 4 groups:
      improvement (IM; improvement in National Institutes of Health Stroke Scale
      [NIHSS] >=4 points), unchanged (UN; no change or decline in NIHSS <4 points),
      exacerbation (EX; decline in NIHSS >=4 points), and re-exacerbation (RE-EX;
      decline of NIHSS >=4 points accompanied by re-exacerbation of neurologic symptoms
      in NIHSS >=4 points). We compared clinical characteristics among the 4 groups.
      RESULTS: Two hundred twenty-two patients (135 men; median age 76 years) were
      enrolled. Sixteen of the 222 (7%) were in the RE-EX group. Small vessel disease
      (SVD), hemorrhagic cerebral infarction, and reocclusion were significantly more
      common among patients in the RE-EX group. SVD, hemorrhagic cerebral infarction,
      and reocclusion occurred in 44%, 25%, and 13% of patients in the RE-EX group, in
      9%, 22%, and 0% of patients in the EX group, in 5%, 6%, and 0% of patients in the
      IM group, and in 17%, 14%, and 1% of patients in the UN group, respectively (P <
      .001, P = .041, and P < .001). Multivariate logistic regression analysis revealed
      that SVD was the only independent factor associated with re-exacerbation within
      24 hours after t-PA infusion (odds ratio 3.52; 95% confidence interval [CI] 1.19
      10.40; P = .023). CONCLUSIONS: Seven percent of patients re-exacerbated within 24
      hours after intravenous infusion of t-PA. Re-exacerbation within 24 hours after t
      PA infusion was strongly associated with SVD.

PMID- 23153552
TI  - Epithelial to mesenchymal transition and cancer stem cell phenotypes leading to
      liver metastasis are abrogated by the novel TGFbeta1-targeting peptides P17 and
      P144.
AB  - Colorectal cancer (CRC) frequently metastasizes to the liver, a phenomenon that
      involves the participation of transforming-growth-factor-beta(1) (TGFbeta(1)).
      Blockade of the protumorigenic effects elicited by TGFbeta(1) in advanced CRC
      could attenuate liver metastasis. We aimed in the present study to assess the
      antimetastatic effect of TGFbeta(1)-blocking peptides P17 and P144, and to study
      mechanisms responsible for this activity in a mouse model. Colon adenocarcinoma
      cells expressing luciferase were pretreated with TGFbeta(1) (Mc38-luc(TGFbeta1)
      cells), injected into the spleen of mice and monitored for tumor development.
      TGFbeta(1) increased primary tumor growth and liver metastasis, whereas systemic
      treatment of mice with either P17 or P144 significantly reduced tumor burden
      (p<0.01). In metastatic nodules, mitotic/apoptotic ratio, mesenchymal traits and
      angiogenesis (evaluated by CD-31, as well as circulating endothelial and
      progenitor cells) induced by TGFbeta(1) were consistently reduced following
      injection of peptides. In vitro experiments revealed a direct effect of
      TGFbeta(1) in Mc38 cells, which resulted in activation of Smad2, Smad3 and
      Smad1/5/8, and increased invasion and transendothelial migration, whereas
      blockade of TGFbeta(1)-signaling reverted these features. Because TGFbeta(1)
      mediated epithelial-mesenchymal transition (EMT) has been suggested to induce a
      cancer stem cell (CSC) phenotype, we analyzed the ability of this cytokine to
      induce tumorsphere formation and the expression of CSC markers. In TGFbeta(1)
      treated cells, tumorspheres were enriched in CD44 and SOX2, which were diminished
      in the presence of P17. Our data provide a preclinical rationale to evaluate P17
      and P144 as potential therapeutic options for the treatment of metastatic CRC.

PMID- 23153553
TI  - Directional cell migration in an extracellular pH gradient: a model study with an
      engineered cell line and primary microvascular endothelial cells.
AB  - Extracellular pH (pH(e)) gradients are characteristic of tumor and wound
      environments. Cell migration in these environments is critical to tumor
      progression and wound healing. While it has been shown previously that cell
      migration can be modulated in conditions of spatially invariant acidic pH(e) due
      to acid-induced activation of cell surface integrin receptors, the effects of
      pH(e) gradients on cell migration remain unknown. Here, we investigate cell
      migration in an extracellular pH(e) gradient, using both model alpha(v)beta(3)
      CHO-B2 cells and primary microvascular endothelial cells. For both cell types, we
      find that the mean cell position shifts toward the acidic end of the gradient
      over time, and that cells preferentially polarize toward the acidic end of the
      gradient during migration. We further demonstrate that cell membrane protrusion
      stability and actin-integrin adhesion complex formation are increased in acidic
      pH(e), which could contribute to the preferential polarization toward acidic
      pH(e) that we observed for cells in pH(e) gradients. These results provide the
      first demonstration of preferential cell migration toward acid in a pH(e)
      gradient, with intriguing implications for directed cell migration in the tumor
      and wound healing environments.

PMID- 23153554
TI  - PGE2 suppresses NK activity in vivo directly and through adrenal hormones:
      effects that cannot be reflected by ex vivo assessment of NK cytotoxicity.
AB  - Surgery can suppress in vivo levels of NK cell cytotoxicity (NKCC) through
      various mechanisms, including catecholamine-, glucocorticoid (CORT)-, and
      prostaglandin (PG)-mediated responses. However, PGs are synthesized locally
      following tissue damage, driving proinflammatory and CORT responses, while their
      systemic levels are often unaffected. Thus, we herein studied the role of adrenal
      factors in mediating in vivo effects of PGs on NKCC, using adrenalectomized and
      sham-operated F344 rats subjected to surgery or PGE(2) administration. In vivo
      and ex vivo approaches were employed, based on intravenous administration of the
      NK-sensitive MADB106 tumor line, and based on ex vivo assessment of YAC-1 and
      MADB106 target-line lysis. Additionally, in vitro studies assessed the kinetics
      of the impact of epinephrine, CORT, and PGE(2) on NKCC. The results indicated
      that suppression of NKCC by epinephrine and PGE(2) are short lasting, and cannot
      be evident when these compounds are removed from the in vitro assay milieu, or in
      the context of ex vivo assessment of NKCC. In contrast, the effects of CORT are
      long-lasting and are reflected in both conditions even after its removal.
      Marginating-pulmonary NKCC was less susceptible to suppression than circulating
      NKCC, when tested against the xenogeneic YAC-1 target line, but not against the
      syngeneic MADB106 line, which seems to involve different cytotoxicity mechanisms.
      Overall, these findings indicate that elevated systemic PG levels can directly
      suppress NKCC in vivo, but following laparotomy adrenal hormones mediate most of
      the effects of endogenously-released PGs. Additionally, the ex vivo approach
      seems limited in reflecting the short-lasting NK-suppressive effects of
      catecholamines and PGs.

PMID- 23153555
TI  - Housing of growing rabbits in individual, bicellular and collective cages: growth
      performance, carcass traits and meat quality.
AB  - During growth (from 27 to 75 days of age), 384 rabbits were kept in different
      types of wire-net cages: 72 individual cages (72 rabbits; 10 animals/m2), 48
      bicellular cages (96 rabbits; 2 rabbits/cage; 18 animals/m2) and 24 collective
      cages (216 rabbits; 9 rabbits/cage; 18 animals/m2). The rabbits housed in
      individual cages showed higher daily weight gain both during the fattening period
      (from 52 to 75 days of age) and during the whole period of growth (43.0 v. 41.8
      and 41.5 g/day; P < 0.05), and they had a higher final live weight at 75 days of
      age (2678 v. 2619 and 2602 g; P < 0.05) compared with the rabbits in the
      bicellular and collective cages, respectively. Rabbits in individual cages
      ingested more feed (133 v. 127 and 126 g/day; P < 0.01), but the feed conversion
      did not differ significantly among rabbits housed in the three types of cages. At
      slaughter, the carcass traits and meat quality were weakly affected by the
      housing system. The transport losses were higher in rabbits kept in individual
      and bicellular cages compared with those reared in collective cages (3.1% and
      2.9% v. 2.2%; P < 0.01). In rabbits kept in individual cages, the hind leg muscle
      to bone ratio was higher (6.35 v. 6.19 and 5.91; P < 0.05) compared with the
      bicellular and collective cages, respectively. The pH and colour of the
      longissimus lumborum did not change with the housing system, while the b* index
      of the biceps femoris was lower (3.04 and 3.32 v. 4.26; P < 0.001) in the rabbits
      kept in individual and bicellular cages, respectively, than in those kept in
      collective cages. In conclusion, the rabbits housed in individual cages showed
      higher daily growth than rabbits kept in bicellular or collective cages, but they
      had a similar feed conversion and carcass quality. Differently, neither in vivo
      performance nor slaughter results differed among the rabbits kept in bicellular
      cages or in collective cages. The meat colour may be affected by the housing
      system, but to an extent that is hardly perceivable by the final consumer.

PMID- 23153556
TI  - Low molecular weight heparins copies: are they considered to be generics or
      biosimilars?
AB  - The protection rights of low molecular weight heparins (LMWHs) are expired or are
      expiring, so the extent and nature of the studies required to obtain a market
      authorization for LMWH copies represents a hot topic. FDA classifies LMWHs as
      semisynthetic drugs and their copies as generics whereas the EMA views them as
      biological medicines and consequently their copies as biosimilars. Consequently,
      FDA requires only in vivo pharmacodynamic studies, while EMA requires also
      clinical trials. The current work reviews the chemical composition and
      therapeutic indications of LMWHs available in the EU and USA markets to discuss
      the two different approaches. Because LMWHs show a high intrinsic variability and
      a complete characterization is not viable, a conservative approach is desirable.

PMID- 23153557
TI  - Alpha B-crystallin prevents the arrhythmogenic effects of particulate matter
      isolated from ambient air by attenuating oxidative stress.
AB  - Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) is activated by
      particulate matter (PM) isolated from ambient air and linked to prolonged
      repolarization and cardiac arrhythmia. We evaluated whether alpha B-crystallin
      (CryAB), a heat shock protein, could prevent the arrhythmogenic effects of PM by
      preventing CaMKII activation. CryAB was delivered into cardiac cells using a TAT
      protein transduction domain (TAT-CryAB). ECGs were measured before and after
      tracheal exposure of diesel exhaust particles (DEP) and each intervention in
      adult Sprague-Dawley rats. After endotracheal exposure of DEP (200 MUg/mL for 30
      minutes, n=11), QT intervals were prolonged from 115+/-14 ms to 144+/-20 ms
      (p=0.03), and premature ventricular contractions were observed more frequently
      (0% vs. 44%) than control (n=5) and TAT-Cry (n=5). However, DEP-induced
      arrhythmia was not observed in TAT-CryAB (1 mg/kg) pretreated rats (n=5). In
      optical mapping of Langendorff-perfused rat heats, compared with baseline, DEP
      infusion of 12.5 MUg/mL (n=12) increased apicobasal action potential duration
      (APD) differences from 2+/-6 ms to 36+/-15 ms (p<0.001), APD restitution slope
      from 0.26+/-0.07 to 1.19+/-0.11 (p<0.001) and ventricular tachycardia (VT) from
      0% to 75% (p<0.001). DEP infusion easily induced spatially discordant alternans.
      However, the effects of DEP were prevented by TAT-CryAB (1mg/kg, n=9). In rat
      myocytes, while DEP increased reactive oxygen species (ROS) generation and
      phosphated CaMKII, TAT-CryAB prevented these effects. In conclusion, CryAB, a
      small heat shock protein, might prevent the arrhythmogenic effects of PM by
      attenuating ROS generation and CaMKII activation.

PMID- 23153558
TI  - Gallic acid inhibits gastric cancer cells metastasis and invasive growth via
      increased expression of RhoB, downregulation of AKT/small GTPase signals and
      inhibition of NF-kappaB activity.
AB  - Our previous study demonstrated the therapeutic potential of gallic acid (GA) for
      controlling tumor metastasis through its inhibitory effect on the motility of AGS
      cells. A noteworthy finding in our previous experiment was increased RhoB
      expression in GA-treated cells. The aim of this study was to evaluate the role of
      RhoB expression on the inhibitory effects of GA on AGS cells. By applying the
      transfection of RhoB siRNA into AGS cells and an animal model, we tested the
      effect of GA on inhibition of tumor growth and RhoB expression. The results
      confirmed that RhoB-siRNA transfection induced GA to inhibit AGS cells' invasive
      growth involving blocking the AKT/small GTPase signals pathway and inhibition of
      NF-kappaB activity. Finally, we evaluated the effect of GA on AGS cell metastasis
      by colonization of tumor cells in nude mice. It showed GA inhibited tumor cells
      growth via the expression of RhoB. These data support the inhibitory effect of GA
      which was shown to inhibit gastric cancer cell metastasis and invasive growth via
      increased expression of RhoB, downregulation of AKT/small GTPase signals and
      inhibition of NF-kappaB activity. Thus, GA might be a potential agent in treating
      gastric cancer.

PMID- 23153559
TI  - Detection of genotoxic and non-genotoxic carcinogens in Xpc(-/-)p53(+/-) mice.
AB  - An accurate assessment of the carcinogenic potential of chemicals and
      pharmaceutical drugs is essential to protect humans and the environment.
      Therefore, substances are extensively tested before they are marketed to the
      public. Currently, the rodent two-year bioassay is still routinely used to assess
      the carcinogenic potential of substances. However, over time it has become clear
      that this assay yields false positive results and also has several economic and
      ethical drawbacks including the use of large numbers of animals, the long
      duration, and the high cost. The need for a suitable alternative assay is
      therefore high. Previously, we have proposed the Xpa*p53 mouse model as a very
      suitable alternative to the two-year bioassay. We now show that the Xpc*p53 mouse
      model preserves all the beneficial traits of the Xpa*p53 model for sub-chronic
      carcinogen identification and can identify both genotoxic and non-genotoxic
      carcinogens. Moreover, Xpc*p53 mice appear to be more responsive than Xpa*p53
      mice towards several genotoxic and non-genotoxic carcinogens. Furthermore,
      Xpc*p53 mice are far less sensitive than Xpa*p53 mice for the toxic activity of
      DNA damaging agents and as such clearly respond in a similar way as wild type
      mice do. These advantageous traits of the Xpc*p53 model make it a better
      alternative for in vivo carcinogen testing than Xpa*p53. This pilot study
      suggests that Xpc*p53 mice are suited for routine sub-chronic testing of both
      genotoxic and non-genotoxic carcinogens and as such represent a suitable
      alternative to possibly replace the murine life time cancer bioassay.

PMID- 23153561
TI  - Use of face masks in a primary care outpatient setting in Hong Kong: Knowledge,
      attitudes and practices.
AB  - OBJECTIVES: To assess if a knowledge gap exists in the correct use of face masks,
      and to explore the correlations between knowledge, attitudes and practices
      regarding the use of face masks among outpatients and their caregivers in an
      outpatient clinic in Hong Kong. STUDY DESIGN: Cross-sectional study. METHODS:
      Outpatients and their caregivers who were present at an outpatient setting in
      Hong Kong were invited to participate in this survey. All participants were asked
      to complete a self-administered closed-ended questionnaire about their knowledge,
      attitudes and practices regarding the use of face masks. Data were described
      using descriptive statistics and correlation coefficients. RESULTS: Among the 399
      respondents, 52% knew the correct steps in wearing a face mask, and their
      attitudes toward face masks were generally positive. Further analyses showed that
      respondents were more likely to wear a face mask at a clinic than in a public
      place or at home. Moreover, respondents were more likely to wear a face mask to
      protect others against influenza-like illness (ILI) than for self-protection.
      There was low to moderate correlation between attitudes and practices
      (correlation coefficient 0.26, P < 0.05). CONCLUSIONS: This study identified a
      knowledge gap in the correct use of face masks among outpatients and their
      caregivers; attitudes and practices regarding the use of face masks were
      generally positive, but correlation was not high. It is recommended that public
      health education campaigns should tailor efficient programmes to combat ILI
      transmission among outpatient clinic populations by improving knowledge about the
      correct use of face masks.

PMID- 23153560
TI  - Sulforaphane is not an effective antagonist of the human pregnane X-receptor in
      vivo.
AB  - Sulforaphane (SFN), is an effective in vitro antagonist of ligand activation of
      the human pregnane and xenobiotic receptor (PXR). PXR mediated CYP3A4 up
      regulation is implicated in adverse drug-drug interactions making identification
      of small molecule antagonists a desirable therapeutic goal. SFN is not an
      antagonist to mouse or rat PXR in vitro; thus, normal rodent species are not
      suitable as in vivo models for human response. To evaluate whether SFN can
      effectively antagonize ligand activation of human PXR in vivo, a three-armed,
      randomized, crossover trial was conducted with 24 healthy adults. The potent PXR
      ligand - rifampicin (300mg/d) was given alone for 7days in arm 1, or in daily
      combination with 450MUmol SFN (Broccoli Sprout extract) in arm 2; SFN was given
      alone in arm 3. Midazolam as an in vivo phenotype marker of CYP3A was
      administered before and after each treatment arm. Rifampicin alone decreased
      midazolam AUC by 70%, indicative of the expected increase in CYP3A4 activity. Co
      treatment with SFN did not reduce CYP3A4 induction. Treatment with SFN alone also
      did not affect CYP3A4 activity in the cohort as a whole, although in the subset
      with the highest basal CYP3A4 activity there was a statistically significant
      increase in midazolam AUC (i.e., decrease in CYP3A4 activity). A parallel study
      in humanized PXR mice yielded similar results. The parallel effects of SFN
      between humanized PXR mice and human subjects demonstrate the predictive value of
      humanized mouse models in situations where species differences in ligand-receptor
      interactions preclude the use of a native mouse model for studying human ligand
      receptor pharmacology.

PMID- 23153562
TI  - Prevalence of overweight/obesity and its association with sedentary behavior in
      children.
AB  - OBJECTIVE: The aim of this study was to determine the prevalence of overweight
      and obesity in children in the northeast region of Portugal, and to examine its
      association with sedentary behavior. METHODS: Data were collected on 1786
      children (907 boys, 879 girls) aged 6 to 13 years. Body mass index was calculated
      from measured height and weight (weight in kg/height in m squared). Overweight
      and obesity were determined using the International Obesity Task Force cutoff
      values. Sedentary behavior was assessed based on means of transport to and from
      school and time spent watching TV and playing video games (TVPC). RESULTS: The
      prevalences of overweight and obesity were 22.6% and 9.4% respectively. The
      differences between the sexes for both overweight and obesity were not
      significant. Most of the children (78.4%) go to school by car. Boys spend more
      time on TVPC than girls, both on weekdays and on weekends. The logistic
      regression model indicated a significant effect of 1.5 hours of TVPC by boys
      during weekdays (OR=0.246; p=0.015). Boys who spent less than 1.5 hours on
      weekdays on TVPC were 75.4% less likely to be overweight than those who spent
      more than 1.5 hours. CONCLUSION: The prevalence of overweight and obesity was
      32%. Only 12.2% of the children spend less than 1.5 hours on TVPC. Boys who spend
      less than 1.5 hours on TVPC are 75.4% less likely to be overweight/obese than
      those who spend more than 1.5 hours.

PMID- 23153563
TI  - The two-cell embryo--two sides of the same coin?

PMID- 23153564
TI  - Seminal plasma induces prostaglandin-endoperoxide synthase (PTGS) 2 expression in
      immortalized human vaginal cells: involvement of semen prostaglandin E2 in PTGS2
      upregulation.
AB  - Inflammation of the cervicovaginal mucosa is considered a risk factor for HIV
      infection in heterosexual transmission. In this context, seminal plasma (SP) may
      play an important role that is not limited to being the main carrier for the
      virions. It is known that SP induces an inflammatory reaction in the cervix
      called postcoital leukocytic reaction, which has been associated with promotion
      of fertility. The mechanisms by which SP triggers this reaction, however, have
      not been clearly established. Previously we reported the expression of
      prostaglandin-endoperoxide synthase 2 (PTGS2), also known as cyclooxygenase 2
      (COX-2), in human vaginal cells in response to toll-like receptor (TLR) ligands
      and other proinflammatory stimuli. In this study, we demonstrate that SP induces
      transcriptional and translational increase of COX-2 expression in human vaginal
      cells and cervicovaginal tissue explants. Furthermore, SP potentiates vaginal
      PTGS2 expression induced by other proinflammatory stimulants, such as TLR ligands
      and a vaginal mucosal irritant (nonoxynol-9) in a synergistic manner. SP-induced
      PTGS2 expression is mediated by intracellular signaling pathways involving MAPKs
      and NF-kappaB. Using fractionation and functional analysis, seminal prostaglandin
      (PG)-E(2) was identified as a one of the major factors in PTGS2 induction. Given
      the critical role of this PG-producing enzyme in mucosal inflammatory processes,
      the finding that SP induces and potentiates the expression of PTGS2 in
      cervicovaginal cells and tissues has mechanistic implications for the role of SP
      in fertility-associated mucosal leukocytic reaction and its potential HIV
      infection-enhancing effect.

PMID- 23153566
TI  - The role of maternal-fetal cholesterol transport in early fetal life: current
      insights.
AB  - The importance of maternal cholesterol as an exogenous cholesterol source for the
      growing embryo was first reported in studies of Smith-Lemli-Opitz syndrome.
      Although most of the fetus's cholesterol is synthesized by the fetus itself,
      there is now growing evidence that during the first weeks of life, when most
      organs develop, the fetus largely depends on maternal cholesterol as its
      cholesterol source. The maternal-fetal cholesterol transport mechanism, by
      transporters in both the yolk sac and placenta, is becoming better understood.
      This minireview summarizes current insights on maternal-fetal cholesterol
      transport based on in vitro and in vivo studies. As the prevalence of maternal
      diseases, such as diabetes, obesity, and the metabolic syndrome that adversely
      affect maternal cholesterol levels, is now rapidly reaching epidemic proportions,
      we urgently need to determine the impact of these maternal conditions on the
      developing human fetus.

PMID- 23153565
TI  - Enhanced genetic integrity in mouse germ cells.
AB  - Genetically based diseases constitute a major human health burden, and de novo
      germline mutations represent a source of heritable genetic alterations that can
      cause such disorders in offspring. The availability of transgenic rodent systems
      with recoverable, mutation reporter genes has been used to assess the occurrence
      of spontaneous point mutations in germline cells. Previous studies using the lacI
      mutation reporter transgenic mouse system showed that the frequency of
      spontaneous mutations is significantly lower in advanced male germ cells than in
      somatic cell types from the same individuals. Here we used this same mutation
      reporter transgene system to show that female germ cells also display a mutation
      frequency that is lower than that in corresponding somatic cells and similar to
      that seen in male germ cells, indicating this is a common feature of germ cells
      in both sexes. In addition, we showed that statistically significant differences
      in mutation frequencies are evident between germ cells and somatic cells in both
      sexes as early as mid-fetal stages in the mouse. Finally, a comparison of the
      mutation frequency in a general population of early type A spermatogonia with
      that in a population enriched for Thy-1-positive spermatogonia suggests there is
      heterogeneity among the early spermatogonial population such that a subset of
      these cells are predestined to form true spermatogonial stem cells. Taken
      together, these results support the disposable soma theory, which posits that
      genetic integrity is normally maintained more stringently in the germ line than
      in the soma and suggests that this is achieved by minimizing the initial
      occurrence of mutations in early germline cells and their subsequent gametogenic
      progeny relative to that in somatic cells.

PMID- 23153567
TI  - Informal payments for maternity health services in public hospitals in Greece.
AB  - BACKGROUND: Private health expenditure for consuming maternity health services
      has been identified as an issue within public hospitals. AIM: To estimate level
      of private health expenditure, in the form of informal payments, for maternal
      services in public hospitals in Greece. METHODS: The study population consisted
      of 160 women who had recently given birth in three provincial general hospitals
      and one general hospital in Athens. A three-part questionnaire was developed in
      order to collect financial information regarding the use of public obstetrics
      services in Greece. RESULTS: The mean age of respondents was 29.5 (+/-5.6) years.
      There was a high rate of informal payments with 74.4% of women involved in
      informal transactions. Mean total private payments were ?1549 (+/-992),
      representing 7.9% of the mean annual per capita income in Greece. Mean informal
      payment was ?848 (+/-714). For 56.3% of the respondents, it was at the
      obstetrician's request, on top of formal payment of ?701 (+/-1351). Total
      informal payments were higher for women who gave birth in Athens (p<0.001), for
      Greek women compared to non Greek (p<0.001) and for deliveries that were
      conducted by women's personal obstetrician (p=0.001). CONCLUSION: There is a
      large black economy in the field of obstetric services, as 74.4% of women who
      used public maternity services had to pay under-the-table payments corresponding
      approximately to the net salary of an intern physician. There is a need for the
      state to adopt innovative strategies and mechanisms in order to reduce informal
      payments for obstetric services in the public sector.

PMID- 23153568
TI  - Mobility of health professionals pre and post 2004 and 2007 EU enlargements:
      evidence from the EU project PROMeTHEUS.
AB  - BACKGROUND: EU enlargement has facilitated the mobility of EU citizens, including
      health professionals, from the 2004 and 2007 EU accession states. Fears have been
      raised about a mass exodus of health professionals and the consequences for the
      operation of health systems. However, to date a systematic analysis of the EU
      enlargement's effects on the mobility of health professionals has been lacking.
      The aim of this article is to shed light on the changes in the scale of movement,
      trends and directions of flows pre and post 2004 and 2007 EU enlargements.
      METHODS: The study follows a pan-European secondary data analysis to (i)
      quantitatively and (ii) qualitatively analyse mobility before and after the EU
      enlargement. (i) The secondary data analysis covers 34 countries (including all
      EU Member States). (ii) Data were triangulated with the findings of 17 country
      case studies to qualitatively assess the effects of enlargement on health
      workforce mobility. RESULTS: The stock of health professionals from the new (EU
      12) into the old EU Member States (EU-15) have increased following EU accession.
      The stock of medical doctors from the EU-12 in the EU-15 countries has more than
      doubled between 2003 and 2007. The available data suggest the same trend for
      dentists. The extremely limited data for nurses show that the stock of nurses
      has, in contrast, only slightly increased. However, while no reliable data is
      available evidence suggests that the number of undocumented or self-employed
      migrant nurses in the home-care sector has significantly increased. Health
      professionals trained in the EU-12 are becoming increasingly important in
      providing sufficient health care in some destination countries and regions facing
      staff shortages. CONCLUSION: A mass exodus of health professionals has not taken
      place after the 2004 and 2007 EU enlargements. The estimated annual outflows from
      the EU-12 countries have rarely exceeded 3% of the domestic workforce. This is
      partly due to labour market restrictions in the destination countries, but also
      to improvements in salaries and working conditions in some source countries. The
      overall mobility of health professionals is hence relatively moderate and in line
      with the overall movement of citizens within the EU. However, for some countries
      even losing small numbers of health professionals can have impacts in underserved
      regions.

PMID- 23153569
TI  - Parent-youth discordance about youth-witnessed violence: associations with trauma
      symptoms and service use in an at-risk sample.
AB  - OBJECTIVE: Studies have consistently demonstrated a lack of agreement between
      youth and parent reports regarding youth-witnessed violence. However, little is
      known about whether disagreement is associated with poorer outcomes and less
      utilization of mental health services. The purpose of the current study was to
      examine disagreement among youth and parents about youth witnessed violence, and
      determine whether concordance predicted trauma symptoms and recognition of need
      and receipt of counseling services. METHODS: Concordance about youth-witnessed
      violence was examined in 766 dyads from the Longitudinal Studies of Child Abuse
      and Neglect (LONGSCAN). Youth participants self-reported trauma symptoms,
      caregivers indicated youth need for and receipt of services. Both youth and
      parents provided information about youth-witnessed violence exposure in the last
      year. RESULTS: Results showed youth and caregivers differed significantly about
      youth-witnessed violence. Specifically, 42% of youth reported youth-witnessed
      violence, compared to only 15% of parents. For those parents who reported youth
      witnessed violence, only 29% reported an identified need for services and only
      17% reported the youth had received any mental health services. Concordance
      between parent-youth dyads was associated with greater identified need for
      services but was not associated with the use of counseling services or trauma
      symptoms. CONCLUSIONS: Youth who reported witnessing violence reported more
      frequent trauma symptoms regardless of concordance. Parents from dyads in which
      both informants reported youth-witnessed violence were more likely to endorse
      need for, but not receipt of counseling services. Given this association between
      youth-witnessed violence and mental health problems, more work is needed to
      identify barriers to concordance as well as service utilization.

PMID- 23153570
TI  - Dexamethasone administration to the neonatal rat results in neurological
      dysfunction at the juvenile stage even at low doses.
AB  - Dexamethasone (DEX), a synthetic glucocorticoid, has been widely used to prevent
      the development of a variety of poor health conditions in premature infants
      including chronic lung disease, inflammation, circulatory failure, and shock.
      Although there are some reports of neurologic complications related to DEX
      exposure, its full effects on the premature brain have not been examined in
      detail. To investigate the effects of DEX on neural development, we first
      administered low doses (0.2 mg/kg bodyweight or less) of the glucocorticoid to
      neonatal rats on a daily basis during the first postnatal week and examined
      subsequent behavioral alterations at the juvenile stage. DEX-treated rats
      exhibited not only a significant reduction in both somatic and brain weights but
      also learning disabilities as revealed in the shuttle avoidance test. The
      hippocampi of DEX-treated rats displayed a high apoptotic and a low mitotic cell
      density compared to control rats on day 7 after birth. In a subsequent
      experiment, neural stem/progenitor cells were cultured in the presence of DEX for
      6 days. The glucocorticoid inhibited cell growth without an increase in cell
      death. These results suggest that administration of DEX to premature infants
      induces neurological dysfunction via inhibition of the proliferation of neural
      stem/progenitor cells.

PMID- 23153571
TI  - Analytical measurement and clinical relevance of vitamin D(3) C3-epimer.
AB  - With an ever-increasing clinical interest in vitamin D insufficiency, numerous
      automated immunoassays, protein binding assays, and in-house LC-MS/MS methods are
      being developed for the quantification of 25-hydroxyvitamin D(3) (25(OH)D(3)).
      Recently, LC-MS/MS methods have identified an epimeric form of 25(OH)D(3) that
      has been shown to contribute significantly to 25(OH)D(3) concentration,
      particularly in infant populations. This review describes the metabolic pathway
      and physiological functions of 3-epi-vitamin D, compares the capability of
      various 25(OH)D(3) methods to detect the epimer, and highlights recent
      publications quantifying 3-epi-25(OH)D(3) in infant, pediatric, and adult
      populations. In total, this review summarizes the information necessary for
      clinicians and laboratorians to decide whether or not to report/consider the C3
      epimer in the analysis and clinical assessment of vitamin D status.

PMID- 23153572
TI  - Subpopulation-proteomics in prokaryotic populations.
AB  - Clonal microbial cells do not behave in an identical manner and form
      subpopulations during cultivation. Besides varying micro-environmental
      conditions, cell inherent features like cell cycle dependent localization and
      concentration of regulatory proteins as well as epigenetic properties are well
      accepted mechanisms creating cell heterogeneity. Another suspected reason is
      molecular noise on the transcriptional and translational level. A promising tool
      to unravel reasons for cell heterogeneity is the combination of cell sorting and
      subpopulation proteomics. This review summarizes recent developments in
      prokaryotic single-cell analytics and provides a workflow for selection of single
      cells, low cell number mass spectrometry, and proteomics evaluation. This
      approach is useful for understanding the dependency of individual cell decisions
      on inherent protein profiles.

PMID- 23153573
TI  - Effect of application mode on interfacial morphology and chemistry between
      dentine and self-etch adhesives.
AB  - OBJECTIVE: To investigate the influence of application mode on the interfacial
      morphology and chemistry between dentine and self-etch adhesives with different
      aggressiveness. METHODS: The occlusal one-third of the crown was removed from un
      erupted human third molars, followed by abrading with 600 grit SiC under water.
      Rectangular dentine slabs were prepared by sectioning the tooth specimens
      perpendicular to the abraded surfaces. The obtained dentine slabs were treated
      with one of the two one-step self-etch adhesives: Adper Easy Bond (AEB, pH~2.5)
      and Adper Prompt L-Pop (APLP, pH~0.8) with (15s, active application) or without
      (15s, inactive application) agitation. The dentine slabs were fractured and the
      exposed adhesive/dentine (A/D) interfaces were examined with micro-Raman
      spectroscopy and scanning electron microscopy (SEM). RESULTS: The interfacial
      morphology, degree of dentine demineralization (DD) and degree of conversion (DC)
      of the strong self-etch adhesive APLP showed more significant dependence on the
      application mode than the mild AEB. APLP exhibited inferior bonding at the A/D
      interface if applied without agitation, evidenced by debonding from the dentine
      substrate. The DDs and DCs of the APLP with agitation were higher than those of
      without agitation in the interface, in contrast to the comparable DD and DC
      values of two AEB specimen groups with different application modes. Raman
      spectral analysis revealed the important role of chemical interaction between
      acid monomers of self-etch adhesives and dentine in the above observations.
      CONCLUSION: The chemical interaction with dentine is especially important for
      improving the DC of the strong self-etching adhesive at the A/D interface.
      Agitation could benefit polymerization efficacy of the strong self-etch adhesive
      through enhancing the chemical interaction with tooth substrate.

PMID- 23153574
TI  - Epigenetics and miRNAs in the diagnosis and treatment of multiple sclerosis.
AB  - The risk of developing multiple sclerosis (MS) depends on both genetic and
      environmental factors. Although the genetic susceptibility to MS has been
      investigated in great detail, reports describing epigenetic changes in the
      context of MS have only recently appeared. Epigenetic changes to DNA influence
      gene expression without altering the underlying DNA sequence. DNA methylation,
      histone modification, and miRNA-associated silencing are the three most important
      epigenetic mechanisms that influence gene expression. In this review, we
      summarize recent studies investigating epigenetic changes and miRNA as biomarkers
      for diagnosing MS and predicting disease course or treatment response. We also
      discuss how the current studies address important clinical questions and how
      future studies could be designed to best inform clinical practice.

PMID- 23153575
TI  - CXCR7 impact on CXCL12 biology and disease.
AB  - It is known that the chemokine receptor CXCR7 (RDC1) can be engaged by both
      chemokines CXCL12 (SDF-1) and CXCL11 (I-TAC), but the exact expression pattern
      and function of CXCR7 is controversial. CXCR7 expression seems to be enhanced
      during pathological inflammation and tumor development, and emerging data suggest
      this receptor is an attractive therapeutic target for autoimmune diseases and
      cancer. CXCR7/CXCR4 heterodimerization, beta-arrestin-mediated signaling, and
      modulation of CXCL12 responsiveness by CXCR7 suggest that the monogamous
      CXCR4/CXCL12 signaling axis is an oversimplified model that needs to be
      revisited. Consequently, research into CXCR7 biology is of great interest and
      further studies are warranted. This review summarizes recent findings about the
      CXCR7 receptor and analyses its impact on understanding the roles of CXCL12
      biology in health and disease.

PMID- 23153576
TI  - Substantia nigra vulnerability after a single moderate diffuse brain injury in
      the rat.

PMID- 23153577
TI  - Hydrogen sulfide inhibits preoptic prostaglandin E2 production during
      endotoxemia.
AB  - Hydrogen sulfide (H(2)S) is a gaseous neuromodulator endogenously produced in the
      brain by the enzyme cystathionine beta-synthase (CBS). We tested the hypothesis
      that H(2)S acts within the anteroventral preoptic region of the hypothalamus
      (AVPO) modulating the production of prostaglandin (PG) E(2) (the proximal
      mediator of fever) and cyclic AMP (cAMP). To this end, we recorded deep body
      temperature (Tb) of rats before and after pharmacological modulation of the CBS
      H(2)S system combined or not with lipopolysaccharide (LPS) exposure, and measured
      the levels of H(2)S, cAMP, and PGE(2) in the AVPO during systemic inflammation.
      Intracerebroventricular (icv) microinjection of aminooxyacetate (AOA, a CBS
      inhibitor; 100 pmol) did not affect basal PGE(2) production and Tb, but enhanced
      LPS-induced PGE(2) production and fever, indicating that endogenous H(2)S plays
      an antipyretic role. In agreement, icv microinjection of a H(2)S donor (Na(2)S;
      260 nmol) reduced the LPS-induced PGE(2) production and fever. Interestingly, we
      observed that the AVPO levels of H(2)S were decreased following the
      immunoinflammatory challenge. Furthermore, fever was associated with decreased
      levels of AVPO cAMP and increased levels of AVPO PGE(2). The LPS-induced
      decreased levels of cAMP were reduced to a lesser extent by the H(2)S donor. The
      LPS-induced PGE(2) production was potentiated by AOA (the CBS inhibitor) and
      inhibited by the H(2)S donor. Our data are consistent with the notion that the
      gaseous messenger H(2)S synthesis is downregulated during endotoxemia favoring
      PGE(2) synthesis and lowering cAMP levels in the preoptic hypothalamus.

PMID- 23153579
TI  - Ischemic conditioning protects the rat retina in an experimental model of early
      type 2 diabetes.
AB  - Diabetic retinopathy is a leading cause of acquired blindness in adults, mostly
      affected by type 2 diabetes mellitus (T2DM). We have developed an experimental
      model of early T2DM in adult rats which mimics some features of human T2DM at its
      initial stages, and provokes significant retinal alterations. We investigated the
      effect of ischemic conditioning on retinal changes induced by the moderate
      metabolic derangement. For this purpose, adult male Wistar rats received a
      control diet or 30% sucrose in the drinking water, and 3 weeks after this
      treatment, animals were injected with vehicle or streptozotocin (STZ, 25mg/kg).
      Retinal ischemia was induced by increasing intraocular pressure to 120 mm Hg for
      5 min; this maneuver started 3 weeks after vehicle or STZ injection and was
      weekly repeated in one eye, while control eyes were submitted to a sham
      procedure. Fasting and postprandial glycemia, and glucose, and insulin tolerance
      tests were analyzed. At 12 weeks of treatment, animals which received a sucrose
      enriched diet and STZ showed significant differences in metabolic tests, as
      compared with control groups. Brief ischemia pulses in one eye and a sham
      procedure in the contralateral eye did not affect glucose metabolism in control
      or diabetic rats. Ischemic pulses reduced the decrease in the electroretinogram a
      wave, b-wave, and oscillatory potential amplitude, and the increase in retinal
      lipid peroxidation, NOS activity, TNFalpha, Muller cells glial fibrillary acidic
      protein, and vascular endothelial growth factor levels observed in diabetic
      animals. In addition, ischemic conditioning prevented the decrease in retinal
      catalase activity induced by T2DM. These results indicate that induction of
      ischemic tolerance could constitute a fertile avenue for the development of new
      therapeutic strategies to treat diabetic retinopathy associated with T2DM.

PMID- 23153578
TI  - Expression of human E46K-mutated alpha-synuclein in BAC-transgenic rats
      replicates early-stage Parkinson's disease features and enhances vulnerability to
      mitochondrial impairment.
AB  - Parkinson's disease (PD), the second most common neurodegenerative disorder, is
      etiologically heterogeneous, with most cases thought to arise from a combination
      of environmental factors and genetic predisposition; about 10% of cases are
      caused by single gene mutations. While neurotoxin models replicate many of the
      key behavioral and neurological features, they often have limited relevance to
      human exposures. Genetic models replicate known disease-causing mutations, but
      are mostly unsuccessful in reproducing major features of PD. In this study, we
      created a BAC (bacterial artificial chromosome) transgenic rat model of PD
      expressing the E46K mutation of alpha-synuclein, which is pathogenic in humans.
      The mutant protein was expressed at levels ~2-3-fold above endogenous alpha
      synuclein levels. At 12 months of age, there was no overt damage to the
      nigrostriatal dopamine system; however, (i) alterations in striatal
      neurotransmitter metabolism, (ii) accumulation and aggregation of alpha-synuclein
      in nigral dopamine neurons, and (iii) evidence of oxidative stress suggest this
      model replicates several preclinical features of PD. Further, when these animals
      were exposed to rotenone, a mitochondrial toxin linked to PD, they showed
      heightened sensitivity, indicating that alpha-synuclein expression modulates the
      vulnerability to mitochondrial impairment. We conclude that these animals are
      well-suited to examination of gene-environment interactions that are relevant to
      PD.

PMID- 23153580
TI  - Magnetic resonance imaging characterization of different experimental autoimmune
      encephalomyelitis models and the therapeutic effect of glatiramer acetate.
AB  - The roles of inflammation and degeneration as well as of gray matter
      abnormalities in multiple sclerosis (MS) and its animal model experimental
      autoimmune encephalomyelitis (EAE) are controversial. We analyzed the
      pathological manifestations in two EAE models, the chronic oligodendrocyte
      glycoprotein (MOG)-induced versus the relapsing-remitting proteolipid protein
      (PLP)-induced, along the disease progression, using advanced magnetic resonance
      imaging (MRI) parameters. The emphasis of this study was the overall assessment
      of the whole brain by histogram analysis, as well as the detection of specific
      affected regions by voxel based analysis (VBA) using quantitative T2,
      magnetization transfer ratio (MTR) and diffusion tensor imaging (DTI). Brains of
      EAE-inflicted mice from both models revealed multiple white and gray matter areas
      with significant changes from naive mice for all MRI parameters. Ventricle
      swelling was more characteristic to the PLP-induced model. Decreased MTR values
      and increased apparent diffusion coefficient (ADC) were observed mainly in MOG
      induced EAE, indicative of macromolecular loss and structural CNS damage
      involvement in the chronic disease. The MS drug glatiramer acetate (GA), applied
      either as prevention or therapeutic treatment, affected all the MRI pathological
      manifestations, resulting in reduced T2 values and ventricle volume, elevated MTR
      and decreased ADC, in comparison to untreated EAE-inflicted mice. In accord,
      immunohistochemical analysis indicated less histological damage and higher amount
      of proliferating oligodendrocyte progenitor cells after GA treatment. The higher
      brain tissue integrity reflected by the MRI parameters on the level of the whole
      brain and in specific regions supports the in situ anti-inflammatory and
      neuroprotective consequences of GA treatment.

PMID- 23153581
TI  - Cbl and Itch binding sites in ERBB4 CYT-1 and CYT-2 mediate K48- and K63
      polyubiquitination, respectively.
AB  - ERBB receptors have an important function in mammalian development and normal
      physiology, but overexpression and poor downregulation of ERBB receptors have
      been associated with malignant growth. Ligand-induced ERBB receptor signaling is
      terminated by clathrin-dependent receptor endocytosis, followed by incorporation
      of activated receptor complexes into multi-vesicular bodies and subsequent
      degradation in lysosomes. In the case of ERBB1, also known as the EGF receptor,
      it has been shown that ubiquitination serves as a signal to facilitate
      internalization and subsequent endosomal sorting, but little is known about the
      role of ubiquitination of other ERBB receptors. In the present study we
      investigated the regulation of ubiquitination and deubiquitination of the ERBB4
      CYT-1 and CYT-2 isoforms in the context of chimeric EGFR-ERBB4 receptors. We
      demonstrate that EGFR-ERBB4 CYT-2 chimera shows decreased ligand-induced
      downregulation and EGF-degradation, as well as enhanced EGF recycling, when
      compared to EGFR-ERBB4 CYT-1. Moreover we show that the mutation Y1103F in the
      binding site for Cbl which is present in both CYT-1 and CYT-2, does not influence
      ERBB4 endosomal trafficking. We further demonstrate that total ligand-induced
      ubiquitination of CYT-1 is higher than that of CYT-2, whereby CYT-1
      ubiquitination is mainly dependent on the PPXY(1056) Itch binding site for the E3
      ligase Itch which is only present in CYT-1, while that of CYT-2 is dependent on
      the Y1103 Cbl binding site. The E3-ligase c-Cbl is more efficiently
      phosphorylated upon EGF stimulation of the CYT-2 than the CYT-1 isoform. Moreover
      our data show that the pY1103 Cbl binding site is required for K48
      polyubiquitination of both CYT-1 and CYT-2, whereas the PPXY(1056) Itch binding
      site is required for K63-polyubiquitination of CYT-1. We further demonstrate that
      EGF stimulation of EGFR-ERBB4 CYT-1 and CYT-2 does not result in efficient
      binding to and tyrosine phosphorylation of the ESCRT-0 subunit Hrs. Finally, even
      though CYT-1 shows ligand-induced K63-polyubiquitination, it is not subjected to
      deubiquitination by the K63 polyubiquitin-specific AMSH deubiquitinating enzyme,
      while CYT-1 is slightly deubiquitinated by USP8. We conclude that Cbl and Itch
      binding sites in ERBB4 CYT-1 and CYT-2 mediate K48- and K63-polyubiquitination,
      respectively.

PMID- 23153582
TI  - Identification of a novel crosstalk between casein kinase 2alpha and NPM-ALK in
      ALK-positive anaplastic large cell lymphoma.
AB  - It was previously reported that beta-catenin contributes to the tumorigenesis of
      ALK-positive anaplastic large cell lymphoma (ALK(+)ALCL), and the oncogenic
      effects of beta-catenin in these tumors are promoted by NPM-ALK, an abnormal
      fusion protein characteristic of ALK(+)ALCL. In this study, we hypothesized that
      NPM-ALK promotes the oncogenic activity of beta-catenin via its functional
      interactions with the Wnt canonical pathway (WCP). To test this hypothesis, we
      examined if NPM-ALK modulates the gene expression of various members in the WCP.
      Using a Wnt pathway-specific oligonucleotide array and Western blots, we found
      that the expression of casein kinase 2alpha (CK2alpha) was substantially
      downregulated in ALK(+)ALCL cells in response to siRNA knockdown of NPM-ALK.
      CK2alpha is biologically important in ALK(+)ALCL, as its inhibition using 4,5,6,7
      tetrabromobenzotriazole or siRNA resulted in a significant decrease in cell
      growth and a substantial decrease in the beta-catenin protein level. Furthermore,
      CK2alpha co-immunoprecipitated with NPM-ALK and regulated its level of serine
      phosphorylation, a feature previously shown to correlate with the oncogenic
      potential of this fusion protein. To conclude, this study has revealed a novel
      crosstalk between NPM-ALK and CK2alpha, and our data supports the model that
      these two molecules work synergistically to promote the tumorigenicity of these
      lymphomas.

PMID- 23153583
TI  - Molecular mechanisms coordinating functional and morphological plasticity at the
      synapse: role of GluA2/N-cadherin interaction-mediated actin signaling in mGluR
      dependent LTD.
AB  - Long-lasting synaptic plasticity involves changes in both synaptic morphology and
      electrical signaling (here referred to as structural and functional plasticity).
      Recent studies have revealed a myriad of molecules and signaling processes that
      are critical for each of these two forms of plasticity, but whether and how they
      are mechanistically linked to achieve coordinated changes remain controversial.
      It is well accepted that functional plasticity at the excitatory synapse is
      dependent upon the activities of glutamate receptors. While the activation of
      NMDARs (N-methyl-D-aspartic acid receptors) and/or mGluRs (metabotropic glutamate
      receptors) is required for the induction of many forms of plasticity, AMPARs
      (alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptors), the
      principal mediators of fast excitatory synaptic transmission, are the ultimate
      targets of modifications that express functional plasticity. Investigations
      exploring structural plasticity have been mainly focused on the small membranous
      protrusions on the dendrites called spines. The morphological regulation of these
      spines is mediated by the reorganization of the actin cytoskeleton, the
      predominant structural component of the synapse. In this regard, the Rho family
      of GTPases, particularly Rac1, RhoA and Cdc42, is found to be the central
      regulator of spine actin and structural plasticity of the synapse. It is thought
      that the collaborative interaction between functional and structural factors
      underlies the sustained or permanent nature of long-lasting synaptic plasticity
      such as long-term potentiation (LTP) and long-term depression (LTD), the most
      extensively studied forms of synaptic plasticity widely regarded as cellular
      mechanisms for learning and memory. However, data specifically pertaining to
      whether and how these two distinct components are linked at the molecular level
      remain sparse. In this regard, we have identified a number of synaptic proteins
      that are involved in both structural and functional changes during mGluR
      dependent LTD (mGluR-LTD). Among these are the GluA2 (formerly called GluR2)
      subunit of AMPARs, Rac1 and Rac1-activated kinases. We have discovered that these
      proteins interact and reciprocally regulate each other, which led us to
      hypothesize that the GluA2-Rac1 interaction may serve as a coordinator between
      functional and morphological plasticity. In this review, we will briefly discuss
      the available evidence to support such a hypothesis.

PMID- 23153584
TI  - LINE-1 ORF-1p functions as a novel androgen receptor co-activator and promotes
      the growth of human prostatic carcinoma cells.
AB  - Widespread interest in the mechanism of transcriptional regulation by the
      androgen receptor (AR) has been stimulated by the finding that AR signaling is
      critically important in the progression of human prostate cancers. Co-factors,
      the co-repressors, or the co-activators are responsible for the regulation of AR
      activation. The pro-oncogene human Long Interspersed Nucleotide acid Element-1
      (LINE-1) encodes LINE-1 ORF-1p and plays important roles in the development and
      progression of several human carcinomas. In this study, the results showed that
      LINE-1 ORF-1p increased the AR transcriptional activity and in turn enhanced the
      expression of prostate specific antigen (PSA) in the presence of R1881. A
      physical protein-protein interaction between the AR signaling and the LINE-1 ORF
      1p was identified by the immunoprecipitation assays and GST pull-down assays.
      Furthermore, LINE-1 ORF-1p would function as a novel AR positive co-regulator
      through modulating its cytoplasm/nucleus translocation and the recruitment to the
      androgen response element in the PSA gene promoter. Our date also showed that the
      LINE-1 ORF-1p promoted the proliferation and anchor-independent growth of LNCaP
      (ligand dependent) and PC-3 (ligand independent) human prostatic carcinoma cells.
      By investigating a novel role of the LINE-1 ORF-1p in the androgen/androgen
      receptor signaling pathway regulation, our study identifies that LINE-1 ORF-1p
      may be a novel AR co-regulator and molecular target for human prostate carcinoma
      therapy.

PMID- 23153585
TI  - Signaling mechanisms and functional roles of cofilin phosphorylation and
      dephosphorylation.
AB  - Cofilin and actin-depolymerizing factor (ADF) are actin-binding proteins that
      play an essential role in regulating actin filament dynamics and reorganization
      by stimulating the severance and depolymerization of actin filaments. Cofilin/ADF
      are inactivated by phosphorylation at the serine residue at position 3 by LIM
      kinases (LIMKs) and testicular protein kinases (TESKs) and are reactivated by
      dephosphorylation by the slingshot (SSH) family of protein phosphatases and
      chronophin. This review describes recent advances in our understanding of the
      signaling mechanisms regulating LIMKs and SSHs and the functional roles of
      cofilin phospho-regulation in cell migration, tumor invasion, mitosis, neuronal
      development, and synaptic plasticity. Accumulating evidence demonstrates that the
      phospho-regulation of cofilin/ADF is a key convergence point of cell signaling
      networks that link extracellular stimuli to actin cytoskeletal dynamics and that
      spatiotemporal control of cofilin/ADF activity by LIMKs and SSHs plays a crucial
      role in a diverse array of cellular and physiological processes. Perturbations in
      the normal control of cofilin/ADF activity underlie many pathological conditions,
      including cancer metastasis and neurological and cardiovascular disorders.

PMID- 23153586
TI  - Regulation of G protein signaling by the 70kDa heat shock protein.
AB  - G protein-coupled receptors (GPCRs) transduce extracellular signals to the
      interior of the cell by activating membrane-bound guanine nucleotide-binding
      regulatory proteins (G proteins). An increasing number of proteins have been
      reported to bind to and regulate GPCRs. We report a novel regulation of the
      alpha(2A) adrenergic receptor (alpha(2A)-R) by the ubiquitous stress-inducible
      70kDa heat shock protein, hsp70. Hsp70, but not hsp90, attenuated G protein
      dependent high affinity agonist binding to the alpha(2A)-R in Sf9 membranes.
      Antagonist binding was unchanged, suggesting that hsp70 uncouples G proteins from
      the receptor. As hsp70 did not bind G proteins but complexed with the alpha(2A)-R
      in intact cells, a direct interaction with the receptor seems likely. In the
      presence of hsp70, alpha(2A)-R-catalyzed [(35)S]GTPgammaS binding was reduced by
      approximately 70%. In contrast, approximately 50-fold higher concentrations of
      hsp70 were required to reduce agonist binding to the stress-inducible 5
      hydroxytryptamine(1A) receptor (5-HT(1A)-R). In heat-stressed CHO cells, the
      alpha(2A)-R was significantly uncoupled from G proteins, coincident with an
      increased localization of hsp70 at the membrane. The contrasting effect of hsp70
      on the alpha(2A)-R compared to the 5-HT(1A)-R suggests that during stress,
      upregulation of hsp70 may attenuate signaling from specific GPCRs as part of the
      stress response to foster survival.

PMID- 23153587
TI  - False lumen stent placement during iatrogenic coronary dissection.
AB  - A 38-year-old woman without significant cardiovascular risk factors was admitted
      in the coronary care unit with the diagnosis of acute coronary syndrome without
      ST-segment elevation. In coronary angiography, left coronary artery system was
      normal in the first contrast injection, but acute occlusion of the left main
      coronary trunk (LCT) due to iatrogenic dissection was observed in the following.
      The patient presented marked ST elevation, severe hypotension, hemodynamic
      collapse, and loss of consciousness. Cardiopulmonary resuscitation (CPR) was
      initiated, and two drug-eluting stents were consecutively placed in the LCT and
      the left anterior descending coronary (LAD), but the patient died after 60 min of
      continuous CPR. The autopsy showed dissection of the LCT and LAD coronaries with
      both stents placed in the false lumen and hyperacute myocardial infarction in the
      anterior left ventricular free wall. This case underlines the importance of
      careful indication of invasive procedures and of taking in consideration their
      potential risks.

PMID- 23153588
TI  - Cyclosporine A and PSC833 inhibit ABCA1 function via direct binding.
AB  - ATP-binding cassette protein A1 (ABCA1) plays a key role in generating high
      density lipoprotein (HDL). However, the detailed mechanism of HDL formation
      remains unclear; in order to reveal it, chemicals that specifically block each
      step of HDL formation would be useful. Cyclosporine A inhibits ABCA1-mediated
      cholesterol efflux, but it is not clear whether this is mediated via inhibition
      of calcineurin. We analyzed the effects of cyclosporine A and related compounds
      on ABCA1 function in BHK/ABCA1 cells. Cyclosporine A, FK506, and pimecrolimus
      inhibited ABCA1-mediated cholesterol efflux in a concentration-dependent manner,
      with IC(50) of 7.6, 13.6, and 7.0MUM, respectively. An mTOR inhibitor, rapamycin
      also inhibited ABCA1, with IC(50) of 18.8MUM. The primary targets for these drugs
      were inhibited at much lower concentrations in BHK/ABCA1 cells, suggesting that
      they were not involved. Binding of [(3)H] cyclosporine A to purified ABCA1 could
      be clearly detected. Furthermore, a non-immunosuppressive cyclosporine, PSC833,
      inhibited ABCA1-mediated cholesterol efflux with IC(50) of 1.9MUM, and
      efficiently competed with [(3)H] cyclosporine A binding to ABCA1. These results
      indicate that cyclosporine A and PSC833 inhibit ABCA1 via direct binding, and
      that the ABCA1 inhibitor PSC833 is an excellent candidate for further
      investigations of the detailed mechanisms underlying formation of HDL.

PMID- 23153589
TI  - Housing of growing rabbits in individual, bicellular and collective cages: fear
      level and behavioural patterns.
AB  - During growth (27 to 75 days of age), a total of 384 rabbits were kept in 72
      individual cages, 48 bicellular cages (2 rabbits/cage) and 24 collective cages (9
      rabbits/cage). To evaluate the effects of the housing system on the fear level
      and behavioural patterns of rabbits at the two ages (39 to 45 days and 66 to 73
      days), a tonic immobility test and an open-field test were conducted and their
      behaviour was video recorded. In the tonic immobility test, the number of
      attempts to induce immobility (1.38) was lower, and the duration of immobility
      (47.8 s) was higher (0.05 < P < 0.01) in the rabbits housed in individual cages
      than in those kept in bicellular (1.72 attempts and 25.0 s of immobility) and
      collective cages (1.99 attempts and 25.0 s of immobility). During the open-field
      test, the rabbits from individual and bicellular cages showed higher latency
      (38.8 and 40.3 v. 27.0 s), a lower number of total (73.3 and 81.7 v. 91.9) and
      central displacements (3.6 and 2.8 v. 5.4) and a shorter running time (11.8 and
      13.6 s v. 17.7 s) and the time biting the pen (5.5 and 9.1 s v. 28.2 s) compared
      with the rabbits kept in collective cages (0.05 < P < 0.001). During the 24-h
      video recording, the rabbits in individual and bicellular cages spent less time
      allogrooming (0.34% and 0.19% v. 1.44%), moving (0.74% and 0.60% v. 1.32%) and
      running (0.08% and 0.03% v. 0.21%) than the rabbits in the collective cages (0.01
      < P < 0.001). The lowest numbers of alerts and hops were observed in the rabbits
      kept in bicellular cages. With increasing age, a lower number of rabbits were
      sensitive to the immobility test and more rabbits entered the pen spontaneously
      during the open-field test (P < 0.001). In conclusion, the rabbits in individual
      cages exhibited the highest fear level and incomplete behavioural patterns; the
      rabbits housed in collective cages showed the lowest fear levels and had the
      possibility of expressing a wider range of behaviour; and the rabbits in
      bicellular cages exhibited an inconsistent pattern of fear in the tonic
      immobility and open-field tests. Probably, these rabbits were in a less stressful
      condition compared with animals in individual cages because social contacts were
      allowed, even if freedom of movement was more limited.

PMID- 23153590
TI  - Analysis of disease recurrence and survival for women with uterine malignancies
      undergoing robotic surgery.
AB  - OBJECTIVES: To evaluate recurrence-free survival (RFS) and overall survival (OS)
      for patients who underwent robotic-assisted laparoscopic hysterectomy (RALH) for
      uterine malignancies. METHODS: Medical records from 372 patients with uterine
      malignancies who underwent RALH from 3/06 to 3/09 at two institutions were
      reviewed for clinico-pathologic data, adjuvant therapies, disease recurrence, and
      survival. Median follow-up for survival analysis was 31 +/- 14 months. Thirty
      (8.1%) patients were lost to follow-up before 12 months and censored from the
      recurrence analysis. RESULTS: Mean age and BMI of 372 patients was 61.8 +/- 9.8
      years and 32.2 +/- 8.4 kg/m(2) (range 19-70). Robotic procedures included RALH 16
      (4.3%), RALH with pelvic lymphadenectomy (PL) 96 (25.8%), and RALH with pelvic
      and-aortic lymphadenectomy (PAL) 252 (67.7%) cases. Histology included 319
      (85.8%) endometrioid and 53 (12.6%) high-risk histologies. Mean pelvic and aortic
      lymph node counts were 16.8 +/- 8.7 and 8.4 +/- 4.5, respectively. Lymph node
      metastases were identified in 26 (7.3%) cases. Adjuvant therapies were prescribed
      for 108 (29.1%) of patients: 7.8% brachytherapy, 1.9% pelvic
      radiation+brachytherapy, 7.8% chemotherapy, 11.6% chemotherapy+radiation. Risk of
      recurrence for all patients was 8.3% and 17 (4.6%) patients died of disease. The
      estimated 3-year recurrence-free survival (RFS) for the entire study group was
      89.3% and the estimated 5-year overall survival (OS) was 89.1%, compared to 92.5%
      and 93.4% for the endometrioid sub-set. CONCLUSIONS: Patients with endometrial
      cancer undergoing robotic hysterectomy with staging lymphadenectomies during our
      3-years of robotic experience had low-risk for recurrence and excellent disease
      specific survival at a median follow-up time of 31 months.

PMID- 23153591
TI  - Old versus new FIGO staging systems in predicting overall survival in patients
      with uterine leiomyosarcoma: a study of 86 cases.
AB  - OBJECTIVES: Uterine leiomyosarcoma (uLMS) was staged using the FIGO system for
      endometrial cancers. The new FIGO system takes into consideration tumor size
      disregarding myometrial and cervical involvement. We aimed to compare the two
      systems and see which more accurately predicts overall survival (OS). METHODS: 86
      patients with uLMS (1984-2010) were retrospectively staged using both FIGO
      systems. Mean OS rates were estimated using the Kaplan-Meier method. RESULTS:
      More patients had stage-I disease by the new FIGO system (42 versus 33). Five
      versus 18 and 27 versus 5 had old and new stage-II and III diseases respectively.
      Five and 4 patients with old stage II and III uLMS respectively were downstaged
      to stage I while 18 with old stage III were downstaged to stage II. Median follow
      up was 23.5 months with a median OS of 114 (95% CI, 61-166) months. Although
      patients with stage I tumors had a higher mean OS rate compared to those with
      higher stage disease by either system, patients with old stage II-IV disease
      showed similar mean OS rates, with stage III-IV patients having a slightly better
      mean OS and a similar trend was observed with the new system. Patients with new
      FIGO stage III had a higher mean OS rate than those with stage II or IV disease
      (37.6 versus 28.1 and 34.3 months). Nonetheless, no statistical significant
      differences were seen in OS according to stage using either system (p=0.786 and
      p=0.400 respectively). CONCLUSION: Neither FIGO staging system is ideal in
      classifying patients into four clinically significant stages.

PMID- 23153592
TI  - [Fondaparinux as an alternative anticoagulant in heparin-induced thrombocytopenia
      in the patient with a ventricular assist device].
AB  - Heparin-induced thrombocytopenia is a reaction associated with the use of this
      drug. It occurs in up to 3% of patients treated for at least 5 days. Its
      treatment is to stop the heparin, and according to patient needs, replace it with
      another anticoagulant. We present a patient who, after a heart transplant, and
      the need for a ventricular assist device, required anticoagulation. The patient
      developed heparin-induced thrombocytopenia. Heparin was stopped and
      anticoagulation was replaced by fondaparinux. The peri-operative complications
      and the management of the coagulation are described. 

PMID- 23153593
TI  - [Epidural and anesthesia for urgent cesarean section in a pregnant woman with
      acute stroke].

PMID- 23153594
TI  - [Bilateral and pneumomediastinal pneumothorax after transoral laser microsurgery
      and tracheotomy].
AB  - Transoral laser CO2 microsurgery is becoming an increasing used treatment option
      for cancer of the larynx and the pharynx. Amongst the advantages it has compared
      to open surgery and radiotherapy are, it less invasiveness, greater precision,
      better functional preservation of the organ, and less procedure-associated
      morbidity. However, this surgical technique is not without its complication, some
      being rare up until now, but with great clinical importance. We present the case
      of a patient subjected to microsurgery with a tracheotomy due to cancer of the
      larynx, who suffered a subcutaneous emphysema, and a bilateral and
      pneumomediastinal pneumothorax, requiring the appropriate measures for its
      control and stabilisation, which are described. A review was also performed of
      the current literature as regards anaesthetic considerations and the main peri
      operative complications of laser microsurgery.

PMID- 23153595
TI  - Plant-pathogen interactions: disease resistance in modern agriculture.
AB  - The growing human population will require a significant increase in agricultural
      production. This challenge is made more difficult by the fact that changes in the
      climatic and environmental conditions under which crops are grown have resulted
      in the appearance of new diseases, whereas genetic changes within the pathogen
      have resulted in the loss of previously effective sources of resistance. To help
      meet this challenge, advanced genetic and statistical methods of analysis have
      been used to identify new resistance genes through global screens, and studies of
      plant-pathogen interactions have been undertaken to uncover the mechanisms by
      which disease resistance is achieved. The informed deployment of major, race
      specific and partial, race-nonspecific resistance, either by conventional
      breeding or transgenic approaches, will enable the production of crop varieties
      with effective resistance without impacting on other agronomically important crop
      traits. Here, we review these recent advances and progress towards the ultimate
      goal of developing disease-resistant crops.

PMID- 23153596
TI  - Our fragile intellect. Part I.
AB  - New developments in genetics, anthropology, and neurobiology predict that a very
      large number of genes underlie our intellectual and emotional abilities, making
      these abilities genetically surprisingly fragile.

PMID- 23153597
TI  - Our fragile intellect. Part II.
AB  - Analysis of human mutation rates and the number of genes required for human
      intellectual and emotional fitness indicates that we are almost certainly losing
      these abilities. If so, how did we get them in the first place, and when did
      things begin to change?

PMID- 23153598
TI  - Patellar eversion does not adversely affect quadriceps recovery following total
      knee arthroplasty.
AB  - Although avoiding patellar eversion during a total knee arthroplasty (TKA) has
      theoretical benefit in quadriceps recovery, there has been paucity of supportive
      objective clinical results. We prospectively designed the study whether TKA
      without patellar eversion has better quadriceps recovery in an objective,
      dynamometer study. Seventy-two knees undergoing TKA with midvastus approach were
      randomized into two groups according to patellar eversion or not. Clinical data
      and objective quadriceps recovery using a dynamometer were investigated
      preoperatively and postoperative at 6weeks, 3months, 6months and 1year. There
      were no statistical differences between two groups throughout the follow-up
      periods in recovery of quadriceps force or power and clinical data. Choosing to
      evert patella during TKA using midvastus approach would not adversely affect
      postoperative quadriceps recovery.

PMID- 23153599
TI  - Diabetes mellitus and the incidence of deep vein thrombosis after total knee
      arthroplasty: a retrospective study.
AB  - We explored if there was an increased risk of DVT in patients with diabetes
      mellitus undergoing total knee arthroplasty within 14days followup. We reviewed
      245 patients undergoing total knee arthroplasty in our hospital between 2003 and
      2011. The incidence of DVT within 14days after operations was compared between
      diabetic patients and non-diabetic patients. There were 37 patients with DVT in
      the diabetes group and 88 in the non-diabetes group within 14days followup
      (p=0.002). The risk of DVT in patients with diabetes mellitus was 2.76 times the
      risk in patients without diabetes mellitus using logistic regression modeling
      (OR=2.76, p=0.003). Although it is still controversial, patients with diabetes
      had a higher incidence rate of DVT after total knee arthroplasty in our study.

PMID- 23153600
TI  - High diversity of Staphylococcus aureus and Staphylococcus pseudintermedius
      lineages and toxigenic traits in healthy pet-owning household members.
      Underestimating normal household contact?
AB  - Forty-three unrelated pet-owning households were screened in Spain to study the
      Staphylococcus aureus and Staphylococcus pseudintermedius nasal carriage, their
      genetic lineages and virulence traits. Sixty-seven healthy owners and 66 healthy
      pets were investigated. Isolates characterization was performed and potential
      interspecies transmission was assessed. S. aureus was present in 51.2% of
      households studied while S. pseudintermedius in 30.2%. Twenty-eight owners
      (41.8%) carried S. aureus: one methicillin-resistant S. aureus (MRSA) [t5173-ST8
      SCCmecIVa] and 27 methicillin-susceptible S. aureus (MSSA). Three owners (4.5%)
      were colonized by methicillin-susceptible S. pseudintermedius (MSSP). Fifteen
      pets (22.7%) carried S. pseudintermedius: two methicillin-resistant S.
      pseudintermedius (MRSP) [ST71-SCCmecII/III; ST92-SCCmecV] and 13 MSSP; in
      addition, 8 pets (12.1%) presented MSSA. High diversity of spa and sequence types
      (STs) was detected. Typical livestock-associated S. aureus lineages (CC398, CC9)
      were observed in humans and/or companion animals and hospital and/or community
      acquired S. aureus lineages (CC45, CC121, CC5, CC8) were detected among pets.
      Almost 40% of S. pseudintermedius were multidrug-resistant. S. aureus isolates
      harboured a remarkable high number of virulence genes. The expA gene was detected
      in 3 S. pseudintermedius isolates. Identical strains from both owners and their
      pets were identified in 5 households (11.6%): (a) four MSSA (t073-ST45/CC45, t159
      ST121/CC121, t209-ST109/CC9, t021-ST1654([new])/singleton) and (b) one multidrug
      resistant MSSP (ST142([new])). Highly clonally diverse and toxigenic S. aureus
      and S. pseudintermedius are common colonizers of healthy humans and pets. The
      presence of these bacterial species, virulence genes, and interspecies
      transmission detected, points out to consider pet ownership as a risk factor to
      acquire, maintain and spread, potential pathogenic bacteria.

PMID- 23153601
TI  - Twin Olympians: the hard science and the lives behind it.

PMID- 23153602
TI  - Design, validity, and reliability of a pediatric resident JumpSTART disaster
      triage scoring instrument.
AB  - OBJECTIVE: To design an instrument for scoring residents learning pediatric
      disaster triage (PDT), and to test the validity and reliability of the
      instrument. METHODS: We designed a checklist-based scoring instrument including
      PDT knowledge and skills and performance, as well as a global assessment.
      Learners' performance in a 10-patient school bus crash simulation was video
      recorded and scored with the instrument. Learners triaged the patients with a
      color-coded algorithm (JumpSTART, Simple Triage and Rapid Treatment). Three
      evaluators observed the recordings and scored triage performance for each
      learner. Internal and construct validity of the instrument were established via
      comparison of resident performance by postgraduate year (PGY) and correlating
      instrument items with overall score. Validity was assessed with analysis of
      variance and the D statistic. We calculated evaluators' intraclass correlation
      coefficient (ICC) for each patient, skill, triage decision, and global
      assessment. RESULTS: There were 37 learners and 111 observations. There was no
      difference in total scores by PGY (P = .77), establishing internal validity.
      Regarding construct validity, most instrument items had a D statistic of >0.5.
      The overall ICC among scores was 0.83 (95% confidence interval [CI] 0.74-0.89).
      Individual patient score reliability was high and was greatest among patients
      with head injury (ICC 0.86; 95% CI 0.79-0.91). Reliability was low for an
      ambulatory patient (ICC 0.29; 95% CI 0.07-0.48). Triage skills evaluation showed
      excellent reliability, including airway management (ICC 0.91; 95% CI 0.86-0.94)
      and triage speed (ICC 0.81; 95% CI 0.72-0.88). The global assessment had moderate
      reliability for skills (ICC 0.63; 95% CI 0.47-0.75) and knowledge (ICC 0.64; 95%
      CI 0.49-0.76). CONCLUSIONS: We report the validity and reliability testing of a
      PDT-scoring instrument. Validity was confirmed with no performance differential
      by PGY. Reliability of the scoring instrument for most patient-level triage,
      knowledge, and specific skills was high.

PMID- 23153603
TI  - New occupational and environmental causes of asthma and extrinsic allergic
      alveolitis.
AB  - Asthma and extrinsic allergic alveolitis (EAA) remain prevalent respiratory
      diseases and the cause of a significant disease burden. This article reviews the
      recent occupational and environmental causes described for these conditions. Even
      over the limited time spam addressed by this article, novel agents and new data
      relating to already suggested causes have been described. Various types of work
      tasks or exposures are described that appear to cause both asthma and EAA.
      Isocyanates, the best example of dual potential to cause asthma and EAA are
      discussed, as is the new understanding of the role metal-working fluids play when
      causing respiratory diseases.

PMID- 23153604
TI  - Work-exacerbated asthma.
AB  - A task force of the American Thoracic Society has defined work-exacerbated asthma
      (WEA) as the worsening of asthma caused by conditions at work. Occupational
      asthma (OA) is asthma that is initiated by occupational exposures in people
      without prior asthma. In contrast, WEA is asthma (already present or coincident
      [new onset]) that is worsened because of conditions at work. This difference is
      critical because asthma is a common disease (present in approximately 7% of
      working adults). Among working adults with asthma, approximately 20% may have
      WEA. WEA has potential implications regarding asthma morbidity, health care use,
      and the economy.

PMID- 23153605
TI  - Occupational chronic obstructive pulmonary disease: an update.
AB  - Chronic obstructive pulmonary disease represents a major cause of morbidity and
      mortality in industrialized and nonindustrialized countries. Although tobacco use
      remains the main factor associated with development of the disease, occupational
      risk factors represent an important and preventable cause. The most common
      occupationally related factors include exposure to organic dusts, metallic fumes,
      and a variety of other mineral gases and/or vapors. This article summarizes the
      literature on the subject and provides an update of the most recent advances in
      the field.

PMID- 23153606
TI  - Occupational rhinitis and other work-related upper respiratory tract conditions.
AB  - The nose and upper airways form the initial area of impact for air pollutants and
      allergens. The development of nasal allergies in the workplace (occupational
      rhinitis) may herald subsequent development of occupational asthma. Exposure
      controls, periodic surveillance, and early intervention may circumvent work
      related airways disease and prevent unnecessary worker impairment and disability.

PMID- 23153607
TI  - Indoor fuel exposure and the lung in both developing and developed countries: an
      update.
AB  - Almost 3 billion people worldwide burn solid fuels indoors. Despite the large
      population at risk worldwide, the effect of exposure to indoor solid fuel smoke
      has not been adequately studied. Indoor air pollution from solid fuel use is
      strongly associated with chronic obstructive pulmonary disease, acute respiratory
      tract infections, and lung cancer, and weakly associated with asthma,
      tuberculosis, and interstitial lung disease. Tobacco use further potentiates the
      development of respiratory disease among subjects exposed to solid fuel smoke.
      There is a need to perform additional interventional studies in this field.

PMID- 23153608
TI  - Newly recognized occupational and environmental causes of chronic terminal
      airways and parenchymal lung disease.
AB  - With the introduction of new materials and changes in manufacturing practices,
      occupational health investigators continue to uncover associations between novel
      exposures and chronic forms of diffuse parenchymal lung disease and terminal
      airways disease. To discern exposure-disease relationships, clinicians must
      maintain a high index of suspicion for the potential toxicity of occupational and
      environmental exposures. This article details several newly recognized chronic
      parenchymal and terminal airways. Diseases related to exposure to indium, nylon
      flock, diacetyl used in the flavorings industry, nanoparticles, and the World
      Trade Center disaster are reviewed. Also reviewed are methods in worker
      surveillance and the potential use of biomarkers in the evaluation of exposure
      disease relationships.

PMID- 23153610
TI  - Military service and lung disease.
AB  - Military personnel can be exposed to toxicants and conditions that can contribute
      to lung diseases. This article describes what is known about these exposures and
      diseases, focusing on the Iraq and Afghanistan wars. Adverse lung health outcomes
      have been reported in US military personnel deployed to Iraq and/or Afghanistan.
      Most studies to date have been hindered by limited deployment-specific exposure
      assessment, lack of baseline lung health information, and variable medical
      evaluations and case definitions. Further research is warranted. Medical
      surveillance has been recommended for returning troops, but the challenges are
      substantial.

PMID- 23153611
TI  - Respiratory health in home and leisure pursuits.
AB  - Many home-based and leisure activities can generate hazardous respirable
      exposures. Routine domestic activities and a variety of hobbies, avocations, and
      leisure pursuits have been associated with a spectrum of respiratory tract
      disorders. Indoor environments present a special risk for high-intensity
      exposures and adverse health effects. There are important knowledge gaps
      regarding the prevalence of specific health hazards within and across
      communities, exposure-response effects, population and individual
      susceptibilities, best management strategies, the adverse health effects of mixed
      exposures, and long-term clinical outcomes following exposures. The home
      environment presents special health risks that should be part of the health
      assessment.

PMID- 23153609
TI  - Occupational and environmental causes of lung cancer.
AB  - Because tobacco smoking is a potent carcinogen, secondary causes of lung cancer
      are often diminished in perceived importance. The goal of this review is to
      describe the occurrence and recent findings of the 27 agents currently listed by
      the International Agency for Research on Cancer (IARC) as lung carcinogens. The
      IARC's updated assessments of lung carcinogens provide a long-overdue resource
      for consensus opinions on the carcinogenic potential of various agents.
      Supplementary new information, with a focus on analytic epidemiologic studies
      that has become available since IARC's most recent evaluation, are also
      discussed.

PMID- 23153612
TI  - Implications of OSA on Work and Work Disability Including Drivers.
AB  - This article illustrates the impact of obstructive sleep apnea (OSA) on the work
      force and emphasizes that there are public health risks and significant societal
      financial losses in untreated OSA. Specifics of OSA impact on individuals are
      discussed with regard to veterans, first responders, farmers, and pilots,
      specially focusing on commercial vehicle drivers. The pathophysiology of OSA and
      the consequence of impairment and disability due to OSA on work capacity are
      introduced. Federal guidelines for occupational-specific recommendations are
      presented. The health care provider's role in identifying and incorporating
      effective screening and treatment strategies for workers with sleep apnea is
      emphasized.

PMID- 23153613
TI  - The classic pneumoconioses: new epidemiological and laboratory observations.
AB  - The purpose of this article is to provide an update on selected issues of current
      interest and recent developments related to 3 types of inorganic mineral dust
      exposures causing classic forms of pneumoconiosis: coal mine dust, crystalline
      silica, and asbestos. Common themes include new imaging modalities, emerging
      exposures, and evolving appreciation of additional adverse health effects
      associated with exposure to these inorganic mineral dusts.

PMID- 23153614
TI  - Respiratory health effects of ambient air pollution: an update.
AB  - There is new evidence for ambient air pollution (AAP) leading to an increased
      incidence of respiratory diseases in adults. Research has demonstrated that co
      exposures have the potential to dramatically augment the effects of AAP and lower
      the threshold of effect of a given pollutant. Interactions between genes related
      to oxidative stress and AAP seem to significantly alter the effect of AAP on an
      individual and population basis. A better definition of vulnerable populations
      may bolster local or regional efforts to remediate AAP. Advances in genetic
      research tools have the potential to identify candidate genes that can guide
      further research.

PMID- 23153615
TI  - Induced sputum, exhaled nitric oxide, and particles in exhaled air in assessing
      airways inflammation in occupational exposures.
AB  - Sensitive methods to detect airways inflammation caused by exposures associated
      with adverse respiratory effects are crucial, as is the identification of
      individuals with early-stage disease. In this review, the use of induced sputum
      and sampling of the fraction of nitric oxide to identify airways inflammation
      associated with occupational exposures is discussed. In addition, a new method to
      assess airways inflammation in small airways (sampling and analyses of particles
      in exhaled air) is introduced.

PMID- 23153616
TI  - Respiratory protection.
AB  - Respiratory protection is used as a method of protecting individuals from
      inhaling harmful airborne contaminants and in some cases to supply them with
      breathable air in oxygen-deficient environments. This article focuses on the use
      and types of personal respiratory protection (respirators) worn by individuals at
      workplaces where airborne hazardous contaminants may exist. Respirators are
      increasingly also being used in nonindustrial settings such as health care
      facilities, as concerns regarding infectious epidemics and terrorist threats
      grow. Pulmonologists and other clinicians should understand fundamental issues
      regarding respiratory protection against airborne contaminants and the use of
      respirators.

PMID- 23153617
TI  - Lung diseases associated with occupational and environmental exposures subsume a
      wide spectrum of conditions.

PMID- 23153618
TI  - Development of solid lipid nanoparticles (SLNs) of lopinavir using hot self nano
      emulsification (SNE) technique.
AB  - Solid lipid nanoparticles (SLNs) of poor orally bioavailable drug lopinavir were
      prepared using hot self nano-emulsification (SNE) technique. Hot isotropic
      mixture of stearic acid, poloxamer and polyethylene glycol was spontaneously self
      nano-emulsify in hot water and SLNs were formed with subsequent rapid cooling.
      Self nano-emulsification ability of stearic acid, poloxamer and polyethylene
      glycol mixture was assessed by ternary phase diagram study. Optimized SLNs were
      having particle size of 180.6 +/- 2.32 nm (PDI=0.133 +/- 0.001), 91.5 +/- 1.3%
      entrapment efficiency and zeta potential of -13.4 +/- 0.56 mV. SLNs were
      evaluated by transmission electron microscopy (TEM) and atomic force microscopy
      (AFM) for morphological study. Further, Differential scanning calorimetry (DSC)
      and X-ray diffraction (XRD) of SLNs were also performed for checking solid state
      characterization. Higher oral bioavailability was found for lopinavir loaded SLNs
      in comparison to bulk lopinavir due to higher lymphatic drug transport (p<0.05).
      Results indicate that SLNs of higher fatty acids can be successfully prepared by
      hot SNE technique.

PMID- 23153619
TI  - The estimation of patient-specific cardiac diastolic functions from clinical
      measurements.
AB  - An unresolved issue in patients with diastolic dysfunction is that the estimation
      of myocardial stiffness cannot be decoupled from diastolic residual active
      tension (AT) because of the impaired ventricular relaxation during diastole. To
      address this problem, this paper presents a method for estimating diastolic
      mechanical parameters of the left ventricle (LV) from cine and tagged MRI
      measurements and LV cavity pressure recordings, separating the passive myocardial
      constitutive properties and diastolic residual AT. Dynamic C1-continuous meshes
      are automatically built from the anatomy and deformation captured from dynamic
      MRI sequences. Diastolic deformation is simulated using a mechanical model that
      combines passive and active material properties. The problem of non-uniqueness of
      constitutive parameter estimation using the well known Guccione law is
      characterized by reformulation of this law. Using this reformulated form, and by
      constraining the constitutive parameters to be constant across time points during
      diastole, we separate the effects of passive constitutive properties and the
      residual AT during diastolic relaxation. Finally, the method is applied to two
      clinical cases and one control, demonstrating that increased residual AT during
      diastole provides a potential novel index for delineating healthy and
      pathological cases.

PMID- 23153621
TI  - Targeting specific traditional risk factors to improve cardiovascular outcomes:
      Sound or flawed?

PMID- 23153620
TI  - Leukotriene A4 hydrolase haplotype, diet and atherosclerosis: a twin study.
AB  - OBJECTIVE: Atherosclerosis is an inflammatory process resulting from the
      interaction between genetic and environmental factors. Leukotrienes are
      inflammatory mediators generated from arachidonic acid, and genetic polymorphisms
      involved in leukotriene metabolism are implicated in atherosclerosis. The
      objectives of this study are to examine whether genetic variants in key
      leukotriene enzymes are associated with atherosclerosis, and whether dietary
      intake of competing leukotriene substrates modifies the effect of leukotriene
      variants on atherosclerosis. METHODS: Atherosclerosis was assessed by common
      carotid intima-media thickness (IMT) using ultrasound. Sequence variants within
      arachidonate 5-lipoxygenase activating protein (ALOX5AP) and leukotriene A4
      hydrolase (LTA4H) genes were analyzed with 32 single nucleotide polymorphisms
      (SNPs) in 169 Caucasian twin pairs from the Vietnam Era Twin Registry. The
      associations between genetic polymorphisms and carotid atherosclerosis, and gene
      * diet interactions were examined by generalized estimating equation controlling
      for potential confounders. RESULTS: A six-SNP haplotype in LTA4H, designated
      HapE, was significantly associated with carotid IMT after adjusting for known
      coronary risk factors. Twins carrying HapE had a much lower IMT compared to twins
      not carrying (695 MUm vs. 750 MUm, p = 0.0007). Moreover, dietary intake of
      polyunsaturated fatty acids strongly augmented the cardioprotective effect of
      HapE among those with this haplotype but not those without, suggesting a
      haplotype * diet interaction (interaction P(HapE*n-3) = 0.03, P(HapE*n-6) =
      0.015). CONCLUSION: We identified a novel leukotriene haplotype that appears to
      be protective toward subclinical atherosclerosis. This association is modified by
      dietary intake of polyunsaturated fatty acids.

PMID- 23153622
TI  - Association of coronary artery calcification and serum gamma-glutamyl transferase
      in Korean.
AB  - BACKGROUND AND OBJECTIVE: Elevated serum gamma-glutamyl transferase (GGT) has
      been known to be associated with the cardiovascular disease. However, there is a
      lack of researches on direct examination of relevance between serum GGT and
      coronary artery calcification (CAC). Accordingly, the aim of this study was to
      investigate the association between serum GGT levels and the prevalence of CAC in
      Korean. METHODS: The study population consisted of 14,439 male and female adults
      without coronary artery disease, who were conducted health examination from
      January 2010 to December 2010. The prevalence of CAC in relation to the quartile
      groups of serum GGT levels and odds ratio and 95% CI of CAC were analyzed using
      multiple logistic regression model. RESULTS: The prevalence of CAC increased with
      increasing GGT quartile (4.6%, 8.7%, 11.8% and 14.7% in the lowest, second,
      third, highest GGT quartiles, respectively; p < 0.001). In the logistic
      regression analysis adjusted for multiple variables, odds ratio (95% CI) for the
      prevalence of CAC comparing the 1st GGT quartile to the 4th quartile were 2.43
      (1.94-3.05) for all subjects, 1.49 (1.21-1.85) for men and 1.33 (0.62-2.87) for
      women. CONCLUSION: Elevated serum GGT levels were independently associated with
      the prevalence of CAC. Physicians and health care providers should be observant
      regarding future development of coronary artery disease among people with
      increasing concentration of serum GGT.

PMID- 23153623
TI  - Influence of omega-3 polyunsaturated fatty acid-supplementation on platelet
      aggregation in humans: a meta-analysis of randomized controlled trials.
AB  - OBJECTIVE: Increased platelet activity predicts adverse cardiovascular events.
      The objective was to assess the effects of long-chain omega-3 polyunsaturated
      fatty acid (n-3 PUFA)-supplementation on platelet aggregation. METHODS AND
      RESULTS: We conducted a meta-analysis of randomized controlled trials identified
      using PubMed, Embase and the Cochrane Library. Fifteen studies were included. In
      comparison to placebo using the random-effect model, n-3 PUFA-supplementation
      significantly reduced adenosine diphosphate-induced platelet aggregation
      (standard mean difference [SMD] = -1.23 with 95% confidence interval [CI] -2.24
      to -0.23, p = 0.02) and platelet aggregation units, determined using the
      VerifyNow((r)) rapid platelet-function assay system (SMD = -6.78 with 95% CI 
      12.58 to -0.98, p = 0.02). There was a trend toward decreased collagen-induced
      (SMD = -0.70 with 95% CI -0.72 to 0.33, p = 0.18) and arachidonic acid-induced
      platelet aggregation (SMD = -0.43 with 95% CI -2.26 to 1.40, p = 0.64) compared
      with controls; however, statistical significance was not reached. CONCLUSIONS:
      Our meta-analysis demonstrates that n-3 PUFA-supplementation is associated with a
      significant reduction in platelet aggregation when the participants were at poor
      health status, but not in healthy persons. High-risk patients with cardiovascular
      disease and even diabetics may potentially benefit from n-3 PUFAs therapy.
      However, n-3 PUFAs may not be effective in primary prevention. Larger trials need
      to be carried out to confirm the present findings.

PMID- 23153624
TI  - Semen preservation and artificial insemination in domesticated South American
      camelids.
AB  - Semen preservation and artificial insemination in South American camelids are
      reviewed giving emphasis to work done in Peru and by the authors. Reports on
      semen evaluation and the preservation process indicate that semen of alpacas and
      llamas can be manipulated by making it liquid first. Collagenase appears to be
      the best enzyme to eliminate viscosity. Tris buffer solution maintains a higher
      motility than egg-yolk citrate, phosphate buffered saline (PBS), Triladyl, and
      Merck-I extenders. Cooling of semen took 1h after collected, and equilibrated
      with 7% glycerol presented a better motility and spermatozoa survival at 1, 7, 15
      and 30days after being slowly frozen in 0.25mL plastic straws. Trials of
      artificial insemination with freshly diluted semen and frozen-thawed semen are
      encouraging and needs to be tested extensively under field conditions. Recently,
      fertility rates varied from 3 to 67%. Semen preservation and most important,
      artificial insemination appear to be a reality, and could be used to improve the
      genetic quality of alpacas and llamas.

PMID- 23153625
TI  - Artificial insemination in dromedary camels.
AB  - Artificial insemination (AI) is an important technique in all domestic species to
      ensure rapid genetic progress. The use of AI has been reported in camelids
      although insemination trials are rare. This could be because of the difficulties
      involved in collecting as well as handling the semen due to the gelatinous nature
      of the seminal plasma. In addition, as all camelids are induced ovulators, the
      females need to be induced to ovulate before being inseminated. This paper
      discusses the different methods for collection of camel semen and describes how
      the semen concentration and morphology are analyzed. It also examines the use of
      different buffers for liquid storage of fresh and chilled semen, the ideal number
      of live sperm to inseminate and whether pregnancy rates are improved if the
      animal is inseminated at the tip of the uterine horn verses in the uterine body.
      Various methods to induce ovulation in the female camels are also described as
      well as the timing of insemination in relation to ovulation. Results show that
      collection of semen is best achieved using an artificial vagina, and the highest
      pregnancy rates are obtained if a minimum of 150*10(6) live spermatozoa (diluted
      in Green Buffer, lactose (11%), or I.N.R.A. 96) are inseminated into the body of
      the uterus 24h after the GnRH injection, given to the female camel to induce
      ovulation. Deep freezing of camel semen is proving to be a great challenge but
      the use of various freezing protocols, different diluents and different packaging
      methods (straws verses pellets) will be discussed. Preliminary results indicate
      that Green and Clear Buffer for Camel Semen is the best diluent to use for
      freezing dromedary semen and that freezing in pellets rather than straws result
      in higher post-thaw motility. Preservation of semen by deep-freezing is very
      important in camelids as it prevents the need to transport animals between farms
      and it extends the reproductive life span of the male, therefore further work
      needs to be carried out to improve the fertility of frozen/thawed camel
      spermatozoa.

PMID- 23153626
TI  - Development of a large commercial camel embryo transfer program: 20 years of
      scientific research.
AB  - Embryo transfer in camels was initiated to respond to demand from the camel
      industry particularly in the United Arab Emirates since 1990. This paper reviews
      the research performed in critical areas of reproductive physiology and
      reproductive function evaluation that constitute a pre-requisite for a successful
      embryo transfer program. A description of donor and recipient management as well
      as a retrospective evaluation of calf production in the embryo transfer program
      at Sweihan, UAE is provided. The program utilized two management systems for
      donors, with and without ovarian superstimulation. Non-stimulated donors are
      flushed every 14-15 days with a mean embryo production per year per female of
      8.5+/-3.1 (mean+/-SEM). Response to gonadotropin stimulation is extremely
      variable. FSH doses and frequency of administration is often adjusted to a
      specific female. In the period of 1990-2010, 11,477 embryos were transferred to
      recipients. Transfers from 1990 to 2009 (n=10,600) resulted in 2858 weaned
      calves, representing an overall efficiency (% weaned calves/transfer) of 27%.
      Pregnancy rates at 60 days post transfer varied from 19 to 44%. Pregnancy length
      following transfer is extremely variable. A major challenge in a large embryo
      transfer program is finding good quality recipients. Causes of pregnancy and
      neonatal losses are under study.

PMID- 23153627
TI  - Survey of accidental dural puncture rates by anaesthetic trainees using constant
      or intermittent plunger pressure.

PMID- 23153629
TI  - Effect of different pre-irradiation times on curcumin-mediated photodynamic
      therapy against planktonic cultures and biofilms of Candida spp.
AB  - OBJECTIVES: The aim of this study was to evaluate the effects of pre-irradiation
      time (PIT) on curcumin (Cur)-mediated photodynamic therapy (PDT) against
      planktonic and biofilm cultures of reference strains of Candida albicans, Candida
      glabrata and Candida dubliniensis. MATERIALS AND METHODS: Suspensions and
      biofilms of Candida species were maintained in contact with different
      concentrations of Cur for time intervals of 1, 5, 10 and 20min before irradiation
      and LED (light emitting diode) activation. Additional samples were treated only
      with Cur, without illumination, or only with light, without Cur. Control samples
      received neither light nor Cur. After PDT, suspensions were plated on Sabouraud
      Dextrose Agar, while biofilm results were obtained using the XTT-salt reduction
      method. Confocal Laser Scanning Microscopy (CLSM) observations were performed to
      supply a better understanding of Cur penetration through the biofilms after 5 and
      20min of contact with the cultures. RESULTS: Different PITs showed no statistical
      differences in Cur-mediated PDT of Candida spp. cell suspensions. There was
      complete inactivation of the three Candida species with the association of
      20.0MUM Cur after 5, 10 and 20min of PIT. Biofilm cultures showed significant
      reduction in cell viability after PDT. In general, the three Candida species
      evaluated in this study suffered higher reductions in cell viability with the
      association of 40.0MUM Cur and 20min of PIT. Additionally, CLSM observations
      showed different intensities of fluorescence emissions after 5 and 20min of
      incubation. CONCLUSION: Photoinactivation of planktonic cultures was not PIT
      dependent. PIT-dependence of the biofilm cultures differed among the species
      evaluated. Also, CLSM observations confirmed the need of higher time intervals
      for the Cur to penetrate biofilm structures.

PMID- 23153628
TI  - Adipocytokine signaling is altered in Flinders sensitive line rats, and
      adiponectin correlates in humans with some symptoms of depression.
AB  - Major depression is a complex multi-factorial disorder with a lifetime diagnosis
      of nearly 1 out of 6. We used the Flinders Sensitive Line (FSL) of rats, a model
      of depression, and the parent Sprague-Dawley (SD) rats to identify genes, gene
      ontology categories and pathways associated with depression. Depression-like
      behavior was verified in the FSL line by forced swim testing, with FSL animals
      exhibiting greater immobility compared to SD rats. RNA samples from the
      hippocampus were isolated from a group of experimentally naive FSL and SD rats
      for microarray analysis. Microarray analysis yielded a total of 361 genes that
      were differentially regulated between FSL and SD rats, with catechol-O
      methyltransferase (COMT) being the most up-regulated. The genes that were
      differentially regulated between FSL and SD rats were subjected to bioinformatic
      analysis using the Database for Annotation, Visualization and Integrated
      Discovery (DAVID), which yielded several gene ontology categories that were
      overrepresented. Subsequent pathway analysis indicated dysregulation of the
      adipocytokine signaling pathway. To test the translational impact of this
      pathway, metabolic factors and psychiatric symptoms were evaluated in a sample of
      human research participants. Results from our human subjects indicated that
      anxiety and a subset of depressive symptoms were correlated with adiponectin
      levels (but not leptin levels). Our results and those of others suggest that
      disruption of the adipocytokine signaling pathway may be a critical component of
      the depressive-like behaviors observed in the FSL rats and may also be an
      important indicator of depressive and anxiety symptoms in humans.

PMID- 23153630
TI  - Unusual case of oral chronic lymphocytic leukemia presenting as recurrent
      epistaxis and asymptomatic intraoral swelling.
AB  - INTRODUCTION: Usually, oral manifestations of chronic lymphocytic leukemia CLL
      are related to an advanced stage of a diagnosed disease, and rarely may lead to
      diagnosis. CLL can also present as bleeding, rarely isolated. We report a rare
      case of CLL the first symptoms of which were recurrent epistaxis and asymptomatic
      intraoral swelling. CASE PRESENTATION: A 74-year-old woman consulted for
      recurrent epistaxis. She presented with a small asymptomatic swelling in the left
      superior vestibule. Computed tomography revealed a tissular-like mass without
      invasion of surrounding tissues. The hemogram revealed thrombocytopenia and
      leukocytosis with 51% of lymphocytes. The immuno-histochemical analysis of the
      lesion and of the bone marrow allowed diagnosing stage IV CLL. DISCUSSION: CLL
      may present as unusual symptoms. It should be suspected in elderly patients
      presenting with atypical clinical signs such as oral swelling or signs of bone
      marrow involvement.

PMID- 23153631
TI  - [Schmid-Meyer fronto-temporal flap for nasal reconstruction].
AB  - INTRODUCTION: Many surgical techniques have already been described to repair full
      thickness defects of the inferior part of the nose. The Schmid-Meyer fronto
      temporal flap procedure, a little known technique, is based on the old principle
      of autonomization of a cutaneous flap and uses a tailor-made composite
      cartilaginous graft placed in the temporal region. This graft is progressively
      detached and allows mucosal/cartilaginous/and cutaneous nasal repair. Can this
      technique still be used for nasal full-thickness reconstruction? PATIENTS AND
      METHOD: Nine cases of nasal reconstruction using this procedure were performed.
      The 4-steps of the operative technique were described and the results were
      analyzed retrospectively. RESULTS: This procedure allows, for some specific
      indications, excellent reconstruction of the ala, the columella or the nasal tip.
      In eight cases out of nine, the result was judged good or very good by both
      patients and physicians. In 78%, the reconstruction was performed under local
      anesthesia. DISCUSSION: The Schmid-Meyer flap procedure may still be used for
      full-thickness reconstruction of the lower third of the nose because it allows a
      high quality of nasal reconstruction and few scar sequels.

PMID- 23153632
TI  - [Treatment of Poland syndrome thorax deformity with the lipomodeling technique:
      about ten cases].
AB  - The correct management, with the classic techniques, of the thoracic deformity in
      Poland's syndrome is difficult, with often insatisfactory results. The current
      surgical treatment involves the use of prothetic material and/or different flaps
      with their own complications and scares. The experience of our team with fat
      grafting (we named lipomodeling) in breast reconstruction helped us to propose
      the correction of the thoracic and mammary deformity by repeated fat transfer
      sessions. Fat grafting is commonly used in our team since 1998 in various
      indication of breast surgery. We reviewed retrospectively our ten first cases of
      thoracic deformity in Poland's syndrome treated with only fat grafting. Patients
      had repeated procedures until obtaining a satisfactory result. The fat was
      harvested from the thigh, buttocks, and abdomen. There were young patients with a
      mean age of 16years old (from 12 to 24). The mean follow-up was 51months. An
      average of 2.9 procedures (1 to 5) with 255cm(3) of fat injection at each
      procedure was needed to obtain symetry. Hundred percent of the patients were
      satisfied. No complication was noted. As reported, the reconstruction of the
      thoracic deformity and the mammary shape can be obtained by fat grafting. The
      absence of a flap donor site sequelae and the absence an implant allow this
      technique to be simple, reproductible, and without great complication. These
      criteria match well the surgical management of this deformity, which is mainly
      aesthetic. Moreover, the secondary benefit of liposuction of disgracious
      steatomery helps the acceptance of the procedure. Therefore in our hands, fat
      grafting to the breast (lipomodeling) is now our first choice treatment in
      thoracic Poland syndrome deformity. Given the rarity of this syndrome, we
      recommend a treatment by an operator who makes the learning curve of
      lipomodeling, and who often deals with Poland syndrome.

PMID- 23153633
TI  - [Strategies in case of unusable internal mammary vessels in a mammary
      reconstruction by DIEP].
AB  - INTRODUCTION: We analyzed the strategy of microvascular connection during the
      DIEP in case of unusable internal mammary vessels in intraoperative period.
      MATERIAL AND METHOD: It is about five cases of mammary reconstructions by DIEP
      practiced in a plastic surgery department. We modified our connections because
      the quality of the artery and/or the vein was considered insufficient. RESULTS:
      In case of internal mammary artery unusable, we changed the donor site and the
      flap was anastomosed with circumflexe scapular vessels. In case of internal
      mammary vein judged unusable but with usable artery, we anastomosed the DIEP with
      the internal mammary artery and with the cephalic vein. We added a venous
      substitution by the second connection with the deep inferior epigastric venous by
      coupler's technique. CONCLUSION: Circumflexe scapular artery was the first
      alternative of internal mammary artery. In every case we protected the
      thoracodorsal pedicle.

PMID- 23153634
TI  - [Treatment of facial paralysis with temporalis lengthening myoplasty and
      dysarthria improvement].
AB  - INTRODUCTION: The dysfunctions engendered by the peripheral facial paralysis
      (PFP) induce modifications of the verbal and para-verbal functions. The purpose
      of our study was to observe if the temporalis lengthening myoplasty (TLM) allowed
      to decrease dysarthria observed on the operated patients. MATERIALS AND METHODS:
      We followed-up seven patients affected by a peripheral facial paralysis with
      various etiologies. Due to specifics needs of this study, we created an
      evaluation grid of the articulation, which allowed us to measure evolutions after
      the operation by a tri-phase evaluation: before surgery, at 3 and 6months after
      it. RESULTS: Results show a definite improvement of dysarthria in the whole test
      group. CONCLUSION: TLM operation, in addition to be very efficient for the
      recovering of the paralyzed side, can also treat dysarthria on these patients.

PMID- 23153635
TI  - Implementing a Virtual Exchange Project for student nurses in Queensland and
      Nottingham.
AB  - This paper discusses the design and initial progress made with a virtual learning
      environment to help student nurses develop an understanding of cultural awareness
      and globalization. Using a Web-based application the Virtual Exchange Project was
      designed to facilitate study-elsewhere experiences located in the student's own
      setting. Promotion of the United Nations' Millennium Development goals provided
      an opportunity for student nurses to explore changes in global health and disease
      patterns, nursing education and systems of nurse regulation in the United Kingdom
      and Australia. A pedagogical framework created for this activity acknowledges the
      social and academic identities that learners often use, when working together in
      a virtual environment. The architecture of the Virtual Exchange supports local
      conversations about nurse education and health and social issues across
      hemispheres. 

PMID- 23153636
TI  - Study of the specific interaction between L-methionine chromatography support and
      nucleotides.
AB  - The interaction of L-methionine-agarose with 5'-mononucleotide was investigated
      by saturation transfer difference (STD)-nuclear magnetic resonance (NMR)
      spectroscopy. Chromatographic experiments were also performed using homo
      oligonucleotides of distinct molecular masses (1-30 nucleotides) to explore the
      effect of base hydrophobicity, temperature, pH and salt concentration on the
      retention of homo-oligonucleotides to L-methionine-agarose support. With STD-NMR,
      the results reveal that hydrophobic residues, such as the CH3 of thymine and
      adenine, can preferentially recognise the L-methionine side chain of the support.
      Also, 5'-TMP led to more contacts with the support, while 5'-UMP presented fewer
      STD contacts. For 5'-UMP, 5'-CMP and 5'-GMP, the main interaction with the
      support was through the sugar-phosphate backbone. Similar binding profiles were
      obtained using chromatographic experiments. Indeed, 5'-TMP had the highest
      retention time, followed by 5'-GMP, 3'-AMP, 5'-UMP and 5'-CMP. In general, the
      retention factor of homo-oligonucleotides was higher for ammonium sulphate
      concentration 1.5 M. For the polyT3-polyT30 series, the retention time increased
      by about three-fold, indicating that larger homo-oligonucleotides have more
      hydrophobic bases, thus enhancing contact with the L-methionine support. The
      temperature (5, 20 and 35  degrees C) did not influence homo-oligonucleotide
      retention. However, the retention time slightly increased when the pH was lower
      than 9. The STD-NMR technique combined with chromatographic experiments was thus
      successfully used to screen amino acid-nucleotide interactions.

PMID- 23153637
TI  - Evaluation of a direct high-capacity target screening approach for urine drug
      testing using liquid chromatography-time-of-flight mass spectrometry.
AB  - In this study a rapid liquid chromatography-time-of-flight mass spectrometry
      method was developed, validated and applied in order to evaluate the potential of
      this technique for routine urine drug testing. Approximately 800 authentic
      patient samples were analyzed for amphetamines (amphetamine and methamphetamine),
      opiates (morphine, morphine-3-glucuronide, morphine-6-glucuronide, codeine and
      codeine-6-glucuronide) and buprenorphines (buprenorphine and buprenorphine
      glucuronide) using immunochemical screening assays and mass spectrometry
      confirmation methods for comparison. The chromatographic application utilized a
      rapid gradient with high flow and a reversed phase column with 1.8 MUm particles.
      Total analysis time was 4 min. The mass spectrometer operated with an
      electrospray interface in positive mode with a resolution power of >10,000 at m/z
      956. The applied reporting limits were 100 ng/mL for amphetamines and opiates,
      and 5 ng/mL for buprenorphines, with lower limits of quantification were 2.8-41
      ng/mL. Calibration curves showed a linear response with coefficients of
      correlation of 0.97-0.99. The intra- and interday imprecision in quantification
      at the reporting limits were <10% for all analytes but for buprenorphines <20%.
      Method validation data met performance criteria for a qualitative and
      quantitative method. The liquid chromatography-time-of-flight mass spectrometry
      method was found to be more selective than the immunochemical method by producing
      lower rates of false positives (0% for amphetamines and opiates; 3.2% for
      buprenorphines) and negatives (1.8% for amphetamines; 0.6% for opiates; 0% for
      buprenorphines). The overall agreement between the two screening methods was
      between 94.2 and 97.4%. Comparison of data with the confirmation (LC-MS) results
      for all individual 9 analytes showed that most deviating results were produced in
      samples with low levels of analytes. False negatives were mainly related to
      failure of detected peak to meet mass accuracy criteria (+/-20 mDa). False
      positives was related to presence of interfering peaks meeting mass accuracy and
      retention time criteria and occurred mainly at low levels. It is concluded that
      liquid chromatography-time-of-flight mass spectrometry has potential both as a
      complement and as replacement of immunochemical screening assays.

PMID- 23153638
TI  - Determination of cyclic guanosine- and cyclic adenosine monophosphate (cGMP and
      cAMP) in human plasma and animal tissues by solid phase extraction on silica and
      liquid chromatography-triple quadrupole mass spectrometry.
AB  - 3',5'-Cyclic guanosine monophosphate (cGMP) and 3',5'-cyclic adenosine
      monophosphate (cAMP) are essential second messenger molecules. They are involved
      in signal transduction within cells, in physiological functions such as
      neurotransmission and in the modulation of cell growth and differentiation of
      organisms, respectively. A quantitative solid phase extraction method (SPE) based
      on hydrophilic interaction on silica was developed and applied to both plasma and
      tissue samples. The stable isotope-labeled internal standards 2D1, 15N3-3',5'
      cGMP and 13C10, 15N5-3',5'-cAMP were added prior to the sample preparation to
      ensure high precision and accuracy. The samples were analyzed by reversed-phase
      liquid chromatography (RP-LC). Negative electrospray (ESI)-MS/MS was used to
      selectively monitor several transitions of each metabolite. The method for the
      analysis of 3',5'-cAMP and 3',5'-cGMP in plasma was validated in the range of
      0.15-20 ng/mL (R2=0.9996 and 0.9994 for 3',5'-cAMP and 3',5'-cGMP, respectively).
      Basal plasma concentrations for fifteen healthy human patients determined with
      this method varied between 4.66-9.20 ng/mL for 3',5'-cAMP and between 0.30-1.20
      ng/mL for 3',5'-cGMP, with precisions better than 9.1%. 3',5'-cGMP and 3',5'-cAMP
      together with their 2',3'-isomers were also determined in a semi quantitative way
      in animal tissues. The structures of the isomers were confirmed by analysis with
      LC-high resolution time-of-flight MS and subsequently by comparison of retention
      times with standards.

PMID- 23153639
TI  - On-line capillary electrophoresis for enhanced detection sensitivity of feline
      panleukopenia virus.
AB  - A rapid on-line capillary electrophoresis (CE) method for highly sensitive
      detection of DNA molecules with specific lengths was developed based on the
      combination of base stacking (BS) and programmed field strength gradients (PFSG).
      The BS method has been performed for on-column concentration to improve detection
      sensitivity without any modification of the CE system. PFSG increased the
      electrophoretic velocity of DNA molecules, which effectively decreased analysis
      time. Using the BS and PFSG combination, the amplified PCR product (340-bp DNA)
      of cats infected with feline panleukopenia virus was detected within 6.5min.
      Detection sensitivity (~10-fold) was enhanced compared to conventional CE
      analysis. The combined on-line CE/BS-PFSG methodology could be an effectively
      rapid analysis technique for the highly sensitive detection of disease-related
      specific DNA molecules.

PMID- 23153640
TI  - Analysis of new potential anticonvulsant compounds in mice brain tissue by
      SPE/HPLC/DAD.
AB  - This paper describes a novel reversed-phase high performance liquid
      chromatography (RP-HPLC) with photo-diode array detection (DAD) method for the
      determination of three new derivatives of 4-alkyl-5-(3-chlorophenyl)-2,4-dihydro
      3H-1,2,4-triazole-3-thione with different antiepileptic activity in the brains of
      mice treated with the doses of 300mgkg(-1) of body weight. Samples were prepared
      by solid-phase extraction (SPE) method using BAKERBONDTM spe Octadecyl (C(18))
      and analyzed by the use of an isocratic elution mode over an Zorbax Extend-C18
      column (150mm*4.6mm I.D., 5-MUm, Agilent Technologies). The mobile phase
      consisted of 80% methanol (for compound TP-315) and 85% acetonitrile (for
      compound TP-321) for 80% 2-propanol (for TP-323) at a flow rate of 1.0mLmin(-1)
      and 0.5mLmin(-1) in the last case. Gradient elution mode was also proposed for
      all examined analytes in mixture with common antiepileptic drugs: carbamazepine,
      phenobarbital and phenytoin in view of possible synergistic activity. Photodiode
      array investigations of the peaks after degradation studies indicate the
      stability of the compounds under conditions proposed for sample preparation
      procedure. Linear coefficients of correlation (r(2)) were >0.995 for all
      analytes. The proposed strategy gives extraction yields higher than 95% with the
      intra- and inter-day relative standard deviation lower than 3% and 5%,
      respectively. This method was applied to the analysis of brain tissue of mice
      treated with investigated compounds. Obtained results enable to explain the
      differences in their pharmacological activity.

PMID- 23153641
TI  - Comparison of methanol and acetonitrile eluents for the quantitation of chelators
      specific to soft-metal ions by HPLC.
AB  - HPLC eluent systems employing acetonitrile and methanol were evaluated for the
      quantitation of glutathione (GSH) and phytochelatin (PC(n)), a family of peptides
      implicated in heavy-metal detoxification in higher plants. The detection system
      is based on the dequenching of copper(I)-bathocuproine disulfonate and is
      specific for soft-metal chelators. Although both elution systems yielded
      comparable analytical performance for each PC(n), the acetonitrile system had a
      lower sensitivity for GSH and a steadily increasing baseline. The inferior
      properties of the acetonitrile system may be due to complex formation between
      acetonitrile and Cu(I) ions. Both methods were applied to measure peptide levels
      in the primitive red alga Cyanidioschyzon merolae. Coefficients of variation
      (CVs) were less than 5%, except for GSH and PC(4) determinations in the
      acetonitrile system, in cases when CV values were found to be 8.8% and 6.3%,
      respectively. Recoveries were greater than 96%, except for GSH determination in
      the acetonitrile system, with a recovery of 84.4%; however, the concentration
      measured in the acetonitrile system did not differ from that measured in the
      methanol system at a significance level of 0.05.

PMID- 23153642
TI  - Investigation of bioaccumulation profile of oestrogens in zebrafish liver by
      hollow fibre protected liquid phase microextraction with gas chromatography-mass
      spectrometric detection.
AB  - The applicability of hollow fibre protected liquid phase microextraction (HF
      LPME) for the determination of three oestrogens, namely estrone (E1), 17beta
      estradiol (E2) and 17alpha-ethinylestradiol (EE2) from individual zebrafish liver
      samples, in a bioaccumulation study on these organisms, is reported. The
      oestrogens were extracted from single, mechanically crushed and minced livers
      from fish that were heaved in tubes containing water spiked at low concentration
      of the analytes. Extraction was performed with ~3 MUL of toluene contained in the
      hollow fibre. In order to achieve high extraction efficiency, the parameters that
      could affect the effectiveness of HF-LPME were optimized, i.e. the extracting
      organic solvent, extraction time, stirring speed and pH of the aqueous phase. For
      gas chromatography/mass spectrometry (GC/MS) analysis, injection port
      derivatization of the oestrogens with bis(trimethylsilyl)trifluoroacetamide was
      conducted. Under the most favourable extraction and derivatization conditions,
      enrichment factors of 158-279 were obtained. Linearity of the HF-LPME-GC/MS
      method was evaluated from 1 to 50 MUg/L and the coefficient of determination (r2)
      ranged from 0.9687 to 0.9926. The LODs were between 0.017 and 0.033 MUg/L (at a
      signal to noise ratio of 3) with relative standard deviations (RSDs, analytes
      spiked at 5 MUg/L) of between 15 and 17% (n=3).

PMID- 23153643
TI  - High-throughput bioanalytical method for analysis of synthetic cannabinoid
      metabolites in urine using salting-out sample preparation and LC-MS/MS.
AB  - Herbal smoking mixtures which are sold as incense or potpourri and often referred
      to as 'Spice' are actually inactive plant matter adulterated with alkylamino
      indole based synthetic cannabinoids such as JWH-018 and JWH-073. Due to the
      inclusion of five synthetic cannabinoids, including JWH-018 and JWH-073, as
      Schedule I drugs by the Drug Enforcement Agency (DEA) in March 2011, it has
      become necessary for forensic laboratories to develop analytical methods to test
      for the presence of metabolites of synthetic cannabinoids. When a new analyte of
      interest emerges, most laboratories strive to develop a sample preparation
      procedure and validate an analytical method as quickly as possible and therefore,
      rely on effective but time consuming traditional protocols such as solid phase
      and liquid-liquid extraction. This research focuses on the examination of all
      aspects of sample preparation and analytical method development to streamline the
      analysis of four urinary metabolites of JWH-018 and JWH-073. A detailed
      evaluation of the beta-glucuronide hydrolysis step lead to the reduction of time
      required for hydrolysis from 1h at 50 degrees C to only 10min at room
      temperature. By utilizing a salting-out assisted liquid-liquid extraction (SALLE)
      in place of traditional liquid-liquid extraction with a volatile solvent,
      processing time was saved and waste was reduced. The analysis run time was also
      shortened to one-third of a typical published run time by utilizing UPLC with
      isocratic conditions in place of conventional HPLC running a gradient method.

PMID- 23153644
TI  - Synthese and characterization of boronic acid functionalized macroporous uniform
      poly(4-chloromethylstyrene-co-divinylbenzene) particles and its use in the
      isolation of antioxidant compounds from plant extracts.
AB  - Aminophenyl boronic acid (APBA) carrying uniform-macroporous
      poly(chloromethylstyrene-co-divinylbenzene), poly(CMS-co-DVB) particles were
      synthesized for selective separation of cis-diol-containing flavonoids from plant
      extracts. For this purpose, 2.5 MUm polystyrene seed particles were first swelled
      by a mixture of dibutyl phthalate (DBP), toluene and dodecanol, then by a monomer
      mixture including CMS and DVB. The repolymerization of the monomer phase in the
      swollen seed particles provided macroporous and uniform particles, approximately
      7 MUm in size. Chlorine atoms on the surface of these particles were derivatized
      with APBA to gain affinity properties for flavonoids containing vicinal hydroxyl
      groups. Model adsorption studies showed that these particles selectively adsorbed
      quercetin and rutin containing cis-diol groups, but did not adsorb apigenin
      similar to quercetin and not carrying cis-diol groups. These particles were also
      tested in adsorption/desorption studies for ethanol and ethyl acetate extracts of
      the Hypericum perforatum (HP) stems to obtain high antioxidant mixtures. With
      ethanol extract, the antioxidant activity of the desorption solution was a bit
      higher than that of the post-adsorption solutions. However, the DPPH radical
      scavenging activity of the desorption solution decreased with respect to the
      original extract and post-adsorption solutions. A similar result was obtained for
      the antioxidant activity of the desorption solution using ethyl acetate extract.
      An interesting result was obtained that DPPH radical scavenging activity of the
      post-adsorption solution was higher than that of the original ethyl acetate
      extract and desorption solutions. These results were attributed to selective
      adsorption of antioxidant characterized cis-diol-containing apolar molecules much
      more rather than that radical scavenger characterized polar molecules.

PMID- 23153645
TI  - Improving the imprinting effect by optimizing template:monomer:cross-linker
      ratios in a molecularly imprinted polymer for sulfadimethoxine.
AB  - Four non-covalently prepared molecularly imprinted polymers (MIPs) for
      sulfadimethoxine (SDM) were prepared using different ratios of SDM template,
      methacrylic acid monomer, and ethylene glycol dimethacrylate cross-linker. The
      imprinting factor (IF) was calculated by comparing the retention of SDM on the
      imprinted polymer with a comparable non-imprinted polymer. The
      template:monomer:cross-linker ratio of 1:6:20 resulted in an IF of 3.94 which is
      higher than found in previous studies. A significant decrease in IF to 0.89 when
      template:cross-linker ratio was 1:40 contradicts most literature where higher
      cross-linker concentration improves selectivity. IF was 4.36 when 20% water was
      added to the acetonitrile HPLC mobile phase during evaluation. Retention of SDM
      increased as water concentration changed as: 20, 40, 0, 60 and 70%, indicating a
      combination of shape recognition, hydrogen bonding and hydrophobic interactions
      contributing to retention of analyte. The MIP has the potential for use in SPE
      for purification and concentration of SDM and with further optimization, possibly
      direct HPLC analysis.

PMID- 23153646
TI  - Determination of tamsulosin in human plasma by liquid chromatography/tandem mass
      spectrometry and its application to a pharmacokinetic study.
AB  - Tamsulosin, a selective alpha1-adrenoceptor antagonist, is used for the treatment
      of benign prostatic hyperplasia (BPH). We developed and validated a rapid,
      sensitive, and simplified liquid chromatography analytical method utilizing
      tandem mass spectrometry (LC-MS/MS) for the determination of tamsulosin in human
      plasma. After liquid-liquid extraction with methyl t-butyl ether, chromatographic
      separation of tamsulosin was achieved using a reversed-phase Luna C18 column (2.0
      mm * 50 mm, 5 MUm particles) with a mobile phase of 10 mM ammonium formate buffer
      (pH 3.5)-methanol (25:75, v/v) and quantified by MS/MS detection in ESI positive
      ion mode. The flow rate of the mobile phase was 200 MUL/min and the retention
      times of tamsulosin and the internal standard (IS, diphenhydramine) were 0.8 and
      0.9 min, respectively. The calibration curves were linear over a range of 0.01-20
      ng/mL (r>0.999). The lower limit of quantification using 500 MUL of human plasma
      was 0.01 ng/mL. The mean accuracy and precision for intra- and inter-day
      validation of tamsulosin were both within acceptable limits. The present LC-MS/MS
      method showed improved sensitivity for quantification of tamsulosin in human
      plasma compared with previously described analytical methods. The validated
      method was successfully applied to a pharmacokinetic study in humans.

PMID- 23153647
TI  - Molecularly imprinted solid phase extraction of urinary diethyl thiophosphate and
      diethyl dithiophosphate and their analysis by gas chromatography-mass
      spectrometry.
AB  - An analytical method involving molecularly imprinted solid phase extraction
      (MISPE) and gas chromatography-mass spectrometry (GC-MS) was developed for the
      analysis of organophosphates metabolites (diethyl thiophosphate--DETP and diethyl
      dithiophosphate - DEDTP) in human urine samples. A DETP molecularly imprinted
      polymer (MIP) was synthesized using 4-vinylpiridine as the functional monomer and
      ethylene glycol dimethacrylate as the cross-linker. The conditioning step of the
      MISPE was conducted by running 3 mL of acetonitrile, 3 mL of 0.1 mol L-1 dibasic
      phosphate buffer at pH 11 and 2 mL of water through the molecularly imprinted
      polymer (MIP) cartridge. The extraction step was executed using 1.0 mL of a urine
      sample, with the pH previously adjusted to 3.0. Finally, the analytes were eluted
      with 3 mL of acetonitrile and derivatized with 3% 2,3,4,5,6-pentafluorobenzyl
      bromide solution at room temperature for 1h. The sample was analyzed by GC-MS in
      the SIM (selected ion monitoring) mode. Analytical calibration curves for DETP
      and DEDTP were constructed using a pool of urine samples and six levels of
      concentration. The method was found to be linear from 10 to 500 MUg L-1 (r>0.99)
      with limits of quantification of 10 MUg L-1 for both analytes. The within-day and
      between-day precisions were evaluated (as %RSD) and all the results were <15% for
      both analytes. The method was accurate (relative error<+/-15%), with good
      robustness.

PMID- 23153648
TI  - Extension of the survival dimensionality reduction algorithm to detect epistasis
      in competing risks models (SDR-CR).
AB  - BACKGROUND: The discovery and the description of the genetic background of common
      human diseases is hampered by their complexity and dynamic behavior. Appropriate
      bioinformatic tools are needed to account all the facets of complex diseases and
      to this end we recently described the survival dimensionality reduction (SDR)
      algorithm in the effort to model gene-gene interactions in the context of
      survival analysis. When one event precludes the occurrence of another event under
      investigation in the 'competing risk model', survival algorithms require
      particular adjustment to avoid the risk of reporting wrong or biased conclusions.
      METHODS: The SDR algorithm was modified to incorporate the cumulative incidence
      function as well as an adapted version of the Brier score for mutually exclusive
      outcomes, to better search for epistatic models in the competing risk setting.
      The applicability of the new SDR algorithm (SDR-CR) was evaluated using synthetic
      lifetime epistatic datasets with competing risks and on a dataset of scleroderma
      patients. RESULTS/CONCLUSIONS: The SDR-CR algorithms retains a satisfactory power
      to detect the causative variants in simulated datasets under different scenarios
      of sample size and degrees of type I or type II censoring. In the real-world
      dataset, SDR-CR was capable of detecting a significant interaction between the IL
      1alpha C-889T and the IL-1beta C-511T single-nucleotide polymorphisms to predict
      the occurrence of restrictive lung disease vs. isolated pulmonary hypertension.
      We provide an useful extension of the SDR algorithm to analyze epistatic
      interactions in the competing risk settings that may be of use to unveil the
      genetic background of complex human diseases. AVAILABILITY:
      http://sourceforge.net/projects/sdrproject/files/.

PMID- 23153649
TI  - Pyrexia and neurologic outcomes after therapeutic hypothermia for cardiac arrest.
AB  - OBJECTIVE: Therapeutic hypothermia, also known as targeted temperature management
      (TTM), improves clinical outcomes in patients resuscitated from cardiac arrest.
      Hyperthermia after discontinuation of active temperature management ("rebound
      pyrexia") has been observed, but its incidence and association with clinical
      outcomes is poorly described. We hypothesized that rebound pyrexia is common
      after rewarming in post-arrest patients and is associated with poor neurologic
      outcomes. METHODS: Retrospective multicenter US clinical registry study of post
      cardiac arrest patients treated with TTM at 11 hospitals between 5/2005 and
      10/2011. We assessed the incidence of rebound pyrexia (defined as temperature >38
      degrees C) in post-arrest patients treated with TTM and subsequent clinical
      outcomes of survival to discharge and "good" neurologic outcome at discharge,
      defined as cerebral performance category (CPC) 1-2. RESULTS: In this cohort of
      236 post-arrest patients treated with TTM, mean age was 58.1 +/- 15.7 y and
      106/236 (45%) were female. Of patients who survived at least 24h after TTM
      discontinuation (n=167), post-rewarming pyrexia occurred in 69/167 (41%), with a
      median maximum temperature of 38.7 (IQR 38.3-38.9). There were no significant
      differences between patients experiencing any pyrexia and those without pyrexia
      regarding either survival to discharge (37/69 (54%) v 51/98 (52%), p=0.88) or
      good neurologic outcomes (26/37 (70%) v 42/51 (82%), p=0.21). We compared
      patients with marked pyrexia (greater than the median pyrexia of 38.7 degrees C)
      versus those who experienced no pyrexia or milder pyrexia (below the median) and
      found that survival to discharge was not statistically significant (40% v 56%
      p=0.16). However, marked pyrexia was associated with a significantly lower
      proportion of CPC 1-2 survivors (58% v 80% p=0.04). CONCLUSIONS: Rebound pyrexia
      occurred in 41% of TTM-treated post-arrest patients, and was not associated with
      lower survival to discharge or worsened neurologic outcomes. However, among
      patients with pyrexia, higher maximum temperature (>38.7 degrees C) was
      associated with worse neurologic outcomes among survivors to hospital discharge.

PMID- 23153650
TI  - Early antibiotics improve survival following out-of hospital cardiac arrest.
AB  - INTRODUCTION: Therapeutic hypothermia (TH) has become standard management
      following out of hospital cardiac arrest (OHCA). Recent evidence suggests TH
      increases the incidence of pneumonia. We retrospectively assessed infective
      indicators after OHCA and evaluated the effect of antibiotics on survival.
      METHOD: We identified all patients admitted to the ICU of a regional primary
      angioplasty hospital following OHCA from May 2007 to December 2010. We collected
      demographic and outcome data, evidence of infection and the use of antimicrobial
      therapy. RESULTS: 138 patients were admitted to ICU following OHCA. The mortality
      rate was 68.1% with mean ICNARC predicted mortality of 77.5%. Of 138 patients,
      135 (97.8%) had at least one positive marker of infection within 72 h. 53 of 138
      patients (38.4%) received antibiotics during the first 7 days of their ICU stay.
      The hospital mortality rate for these patients was significantly less than those
      not receiving antibiotics (56.6% vs. 75.3%; p=0.025) with NNT of 5. Multivariate
      analysis demonstrated that antibiotic use was an independent predictor of
      survival. CONCLUSION: The post-arrest management of OHCA is commonly complicated
      by infections, the accurate diagnosis of which is impaired by the associated
      increase in inflammatory markers, body temperature control, delay in the
      processing of samples and poor quality chest radiography. We have shown a
      significant reduction in mortality in patients who received antibiotics compared
      with patients who did not. This suggests that a formal clinical trial is
      warranted.

PMID- 23153651
TI  - D-Aspartic acid implication in the modulation of frog brain sex steroid levels.
AB  - There is evidence that D-aspartate (D-Asp) modulates sex hormone levels in frog
      testis by regulating the activity of P450 aromatase (P450 aro), the key enzyme
      which converts Testosterone (T) in 17beta-Estradiol (E2). Here we report, for the
      first time, that there is a direct correlation among brain levels of D-Asp, P450
      aro, E2 and Estradiol Receptor (ERalpha) in the male frogs during the
      reproductive as well as the post-reproductive phases of the breeding cycle, with
      highest levels being observed in the post-reproductive period. D-Asp i.p.
      administration to frogs ready for reproduction, induced an increase of brain P450
      aro protein expression with concomitant enhancement of both E2 levels and ERalpha
      expression; at the same time, brain T levels and Androgen receptor expression
      decreased. In contrast, in the post-reproductive frogs, D-Asp treatment did not
      modify any of these parameters. Taken together, these results imply that the
      regulation of P450 aro expression by D-Asp could be an important step in the
      control of E2 levels in the frog brain.

PMID- 23153652
TI  - Physiologic implications of inter-hormonal interference in fish: lessons from the
      interaction of adrenaline with cortisol and thyroid hormones in climbing perch
      (Anabas testudineus Bloch).
AB  - Adrenaline and cortisol, the major stress hormones, are known for its direct
      control on stress response in fish. Likewise, as an important stress modifier
      hormone, thyroid hormone has also been implicated in stress response of fish. We
      tested whether the hypothesis on the phenomenon of inter-hormonal interference, a
      process that explains the hormonal interactions, operates in fish particularly
      between adrenaline, cortisol and thyroid hormones. To achieve this goal, indices
      of acid-base, osmotic and metabolic regulations were quantified after adrenaline
      challenge in propranolol pre-treated air-breathing fish (Anabas testudineus).
      Short-term adrenaline (10 ng g(-1)) injection for 30 min produced a rise in
      plasma cortisol without affecting plasma T(3) and T(4). On the contrary, blocking
      of adrenaline action with a non-selective blocker, propranolol (25 ng g(-1)) for
      90 min reduced plasma cortisol along with plasma T(4) and that indicate a
      possible interference of these hormones in the absence of adrenaline challenge.
      Similarly, a reduction in plasma T(3) was found after adrenaline challenge in
      propranolol pre-treated fish and that suggests a functional synergistic
      interference of adrenaline with T(3). Adrenaline challenge in these fish,
      however, failed to abolish this propranolol effect. The remarkable systemic
      hypercapnia and acidosis by propranolol pre-treatment were reversed by adrenaline
      challenge, pointing to a direct action of adrenaline on acid-base indices
      probably by a mechanism which may not require beta-adrenergic receptor systems.
      Interestingly, the prominent adrenaline-induced hyperglycemia, hyperlactemia and
      hyperuremea were not altered by propranolol treatment. Similarly, adrenaline
      challenge promoted and propranolol reduced the osmotic competencies of the gills,
      kidneys and liver of this fish as evident in the sodium and proton pump
      activities. The modified physiologic actions of adrenaline and its modified
      interaction with THs and cortisol in blocked fish indicate an interaction of
      adrenaline with cortisol and THs. Our physiologic evidences thus support the
      hypothesis of the phenomenon of inter-hormonal interference.

PMID- 23153653
TI  - Nitric oxide rectifies acid-base disturbance and modifies thyroid hormone
      activity during net confinement of air-breathing fish (Anabas testudineus Bloch).
AB  - Nitric oxide (NO), a short-lived freely diffusible radical gas that acts as an
      important biological signal, regulates an impressive spectrum of physiological
      functions in vertebrates including fishes. The action of NO, however, on thyroid
      hormone status and its role in the integration of acid-base, osmotic and
      metabolic balances during stress are not yet delineated in fish. Sodium
      nitroprusside (SNP), a NO donor, was employed in the present study to investigate
      the role of NO in the stressed air-breathing fish Anabas testudineus. Short-term
      SNP treatment (1 mM; 30 min) interacted negatively with thyroid axis, as evident
      in the fall of plasma thyroxine in both stressed and non-stressed fish. In
      contrast, the cortisol responsiveness to NO was negligible. SNP challenge
      produced systemic alkalosis, hypocapnia and hyperglycemia in non-stressed fish.
      Remarkable acid-base compensation was found in fish kept for 60 min net
      confinement where a rise in blood pH and HCO(3) content occurred with a reduction
      in PCO(2) content. SNP challenge in these fish, on the contrary, produced a rise
      in oxygen load together with hypocapnia but without an effect on HCO(3) content,
      indicating a modulator role of NO in respiratory gas transport during stress
      response. SNP treatment reduced Na(+), K(+) ATPase activity in the gill,
      intestine and liver of both stressed and non-stressed fish, and this suggests
      that stress state has little effect on the NO-driven osmotic competence of these
      organs. On the other hand, a modulatory effect of NO was found in the kidney
      which showed a differential response to SNP, emphasizing a key role of NO in
      kidney ion transport and its sensitivity to stressful condition. H(+)-ATPase
      activity, an index of H(+) secretion, downregulated in all the organs of both non
      stressed and stressed fish except in the gill of non-stressed fish and this
      supports a role for NO in promoting alkalosis. The data indicate that, (1) NO
      interacts antagonistically with T(4), (2) modifies respiratory gas transport and
      (3) integrates acid-base and osmotic actions during stress response in air
      breathing fish. Collectively, this first evidence in fish indicate that NO can
      promote compensatory physiologic modification and that can reduce the magnitude
      of stress-induced acid-base and osmotic disturbance and that suggests a role for
      NO in the ease and ease response of this fish.

PMID- 23153654
TI  - Analysis of the relationships between evolvability, thermodynamics, and the
      functions of intrinsically disordered proteins/regions.
AB  - The evolvability of proteins is not only restricted by functional and structural
      importance, but also by other factors such as gene duplication, protein
      stability, and an organism's robustness. Recently, intrinsically disordered
      proteins (IDPs)/regions (IDRs) have been suggested to play a role in facilitating
      protein evolution. However, the mechanisms by which this occurs remain largely
      unknown. To address this, we have systematically analyzed the relationship
      between the evolvability, stability, and function of IDPs/IDRs. Evolutionary
      analysis shows that more recently emerged IDRs have higher evolutionary rates
      with more functional constraints relaxed (or experiencing more positive
      selection), and that this may have caused accelerated evolution in the flanking
      regions and in the whole protein. A systematic analysis of observed stability
      changes due to single amino acid mutations in IDRs and ordered regions shows that
      while most mutations induce a destabilizing effect in proteins, mutations in IDRs
      cause smaller stability changes than in ordered regions. The weaker impact of
      mutations in IDRs on protein stability may have advantages for protein
      evolvability in the gain of new functions. Interestingly, however, an analysis of
      functional motifs in the PROSITE and ELM databases showed that motifs in IDRs are
      more conserved, characterized by smaller entropy and lower evolutionary rate,
      than in ordered regions. This apparently opposing evolutionary effect may be
      partly due to the flexible nature of motifs in IDRs, which require some key amino
      acid residues to engage in tighter interactions with other molecules. Our study
      suggests that the unique conformational and thermodynamic characteristics of
      IDPs/IDRs play an important role in the evolvability of proteins to gain new
      functions.

PMID- 23153655
TI  - Neurological exotropia: do we need to decrease surgical dosing?

PMID- 23153657
TI  - Grid laser photocoagulation for macular oedema due to branch retinal vein
      occlusion in the age of bevacizumab? Results of a prospective study with
      crossover design.
AB  - BACKGROUND AND AIM: To investigate the long term effectiveness of grid laser
      photocoagulation (GLP) versus intravitreal bevacizumab (BEV) in macular oedema
      (MO) secondary to branch retinal vein occlusion (BRVO), and to evaluate the
      treatment courses after treatments were switched. METHODS: In this prospective
      interventional consecutive case series, previously untreated eyes with perfused
      MO were enclosed over a period of 16 months for BEV and for 29 months for GLP.
      The follow-up period was 1 year. Patients with persistent MO after 12 months of
      BEV were offered GLP and vice versa, and were followed-up for another 12 months.
      RESULTS: Both BEV (23 eyes) and GLP (21 eyes) caused a significant (p<0.05)
      reduction in central retinal thickness (CRT) at 12 months although this was
      delayed with GLP. However, BEV revealed a significantly better best corrected
      visual acuity (BCVA) compared with GLP (0.2 vs 0.5 logMAR; p<0.04). Switching
      therapy for non-responders revealed a reduced CRT at another 12 months, although
      this was not significant. CONCLUSIONS: Functionally and anatomically, BEV appears
      to be more effective than GLP for the therapy of MO due to BRVO. BCVA is
      significantly better after 1 year and the anatomical response of the MO is
      faster. Furthermore, non-responders with persistent MO despite BEV or GLP
      treatment might benefit from switching therapy.

PMID- 23153658
TI  - Clinical and molecular features in patients with advanced non-small-cell lung
      carcinoma refractory to first-line platinum-based chemotherapy.
AB  - Most of the cases of non-small-cell lung cancer (NSCLC) are diagnosed at an
      advanced stage and are treated with platinum-doublet chemotherapy. However, some
      patients are refractory to this treatment. The aim of this study was to identify
      the clinical and molecular characteristics of patients with refractory disease.
      All consecutive patients between 2003 and 2006, who received a platinum-doublet
      chemotherapy as first-line treatment for stage IIIb-IV NSCLC, were included.
      Refractory patients were defined as early progressive disease (PD) at the first
      evaluation of chemotherapy according to WHO criteria. The clinical, histo
      pathological, and molecular characteristics (EGFR: exon 19, 20, 21 and KRAS: exon
      2 by PCR sequencing; ALK by immunohistochemistry) and survival of refractory
      patients with initial PD (r-patients) and controlled disease (c-patients) were
      compared by univariate analyses. Factors that differed between the two groups (p
      value <0.25 in univariate analyses) were entered into multivariate analysis. In
      this study, 178 patients were included. The first tumor assessment was carried
      out after a median of three cycles (range 1-4). Forty-six (25.8%) patients were
      refractory. Clinical presentation was similar between r- and c-patients. The
      sarcomatoid histological subtype was more common in r-patients than c-patients
      (10.9% vs. 1.5%, respectively; p=0.057). The proportion of EGFR (5.2% vs. 9.6%,
      p=0.224) and KRAS mutations (11.1% vs. 5.7%, p=0.357), and the expression of ALK
      (6.3% vs. 2.5%, p=0.327) did not differ significantly between the two groups. In
      multivariate analysis, sarcomatoid histological subtype was the only factor
      associated with early PD (OR=7.50; 95%CI: 1.02-55.45; p=0.048). r-Patients had
      significantly shorter survival than c-patients (median 5 months (IQR 3.2-9.9) vs.
      15.4 months (IQR 9.9-22.5), respectively; p<0.0001). In conclusion, patients with
      early PD under platinum-doublet chemotherapy had shorter survival than c
      patients. Sarcomatoid histological subtype was the only independent factor
      associated with early PD.

PMID- 23153659
TI  - The influence of time of radio-chemotherapy and other therapeutic factors on
      treatment results in patients with limited disease small cell lung cancer.
AB  - PURPOSE: The evaluation of effect of therapeutic parameters such as time of
      starting thoracic radiotherapy in relation to chemotherapy, schedule of
      combination chemo- and radiotherapy and SER, on treatment results in patients
      with limited disease small cell lung cancer (LD SCLC). METHODS: Between 2000 and
      2007, 212 patients with LD SCLC received combined therapy: chemotherapy and
      thoracic radiotherapy. All patients received chemotherapy according to PE
      schedule (4-6 cycles), in combination with thoracic radiotherapy. The total dose
      applied to GTV was 54 Gy given in 27-30 fractions using fraction dose of 1.8-2.0
      Gy. The concurrent treatment was performed in 112 patients (52.8%): the
      conventional fractionation (once a day, every five days a week) in 35 patients
      while 77 patients received "moderate" accelerated fractionation (one fraction a
      day, every four days a week and two fractions within one day, a week apart, with
      6h gap). The remaining 100 patients (47.2%) received sequential treatment. The
      time from the first day of chemotherapy to the end of thoracic radiotherapy (SER)
      was evaluated in all patients. The SER ranged from 57 to 337 days with the median
      value of 121 days. RESULTS: The complete response in the thorax was observed in
      143 out of 212 patients (67.5%). Out of these, 82 patients received concurrent
      chemo-radiotherapy (given in 22 patients as conventional dose fractionation and
      in 60 patients according to "moderate" accelerated dose fractionation), and the
      remaining 61 patients were treated with sequential therapy. The 5-year survival
      rates were: 17.7% for overall survival (OS), and 19.3% for disease-free survival
      (DFS). The relationship of therapeutic factors to survival rates showed
      statistically significant improvement of survival ratios in relation to early
      starting of thoracic radiotherapy and application of concurrent chemo
      radiotherapy. The results of logistic regression revealed significant
      relationship between the value of SER and OS and DFS. The analysis shows that
      each day of extension of the SER resulted in increased probability of death
      (decrease of OS) by 0.28% and in increased the risk of development failure
      (decrease of DFS) by 0.31%. The influence of SER on lowered probability of
      complete response frequency was not statistically significant. CONCLUSIONS: The
      concurrent chemo-radiotherapy with early administration of thoracic radiotherapy,
      results in improved complete response in the thorax and increase of overall and
      disease-free survival rates. The 5-year survival rates were: 17.7% for overall
      survival and 19.3% for disease-free survival. Our analysis and data from the
      literature suggest that shorter SER may play prognostic role in patients with LD
      SCLC treated with combination chemo- and radiotherapy. However, these
      observations require the confirmation in following studies.

PMID- 23153660
TI  - Comparative multidatabase analysis of dosing patterns and infusion intervals for
      the first 12 infliximab infusions in patients with rheumatoid arthritis.
AB  - BACKGROUND: According to prescribing information for rheumatoid arthritis (RA)
      treatments in the United States, infliximab should be administered at weeks 1, 2,
      6, and then every 8 weeks starting at a 3-mg/kg dose, with flexible dosing up to
      10 mg/kg and/or every 4 weeks based on clinical response. OBJECTIVE: This study
      evaluated dosing and intervals of the first 12 infliximab infusions in patients
      with RA across multiple large administrative databases. METHODS: Data were
      obtained from 4 databases: HealthCore Integrated Research Database (HIRD), IMS
      LifeLink Health Plan Claims Database (IMS Lifelink), Premier Perspective Database
      (PPD), and Wolters Kluwer Pharma Solutions (WKPS). Patients were aged >=18 years,
      diagnosed with RA, and naive to biologic therapy. Patients with other select
      inflammatory conditions were excluded. The induction period included infusions 1
      through 3; the maintenance period included infusions 4 through 12. RESULTS:
      Observed dosing patterns from the HIRD, IMS LifeLink, PPD, and WKPS databases
      demonstrated minimal dose increases from the first infusion (93.5, 103.3, 58.8,
      and 73.2 mg, respectively) and from the first maintenance infusion (69.1, 64.3,
      45.7, and 45.7 mg, respectively) to the highest dose during the first 12
      infusions. The mean number of days between infusions in the maintenance period
      ranged from 53.3 to 63.5 in HIRD, 53.7 to 60.3 in IMS LifeLink, 53.4 to 59.4 in
      PPD, and 52.3 to 55.0 in the WKPS database. CONCLUSION: Data from multiple
      databases of patients with RA suggest that, in clinical practice, infliximab
      dosing and intervals are consistent with FDA prescribing information and remain
      relatively stable during the first 12 infusions.

PMID- 23153661
TI  - Limited sampling estimates of epigallocatechin gallate exposures in cirrhotic and
      noncirrhotic patients with hepatitis C after single oral doses of green tea
      extract.
AB  - BACKGROUND: Epigallocatechin-3-gallate (EGCG) has antiangiogenic, antioxidant,
      and antifibrotic properties that may have therapeutic potential for the treatment
      of cirrhosis induced by hepatitis C virus (HCV). However, cirrhosis might affect
      EGCG disposition and augment its reported dose-dependent hepatotoxic potential.
      OBJECTIVE: The safety, tolerability, and disposition of a single oral dose of
      EGCG in cirrhotic patients with HCV were examined in an exploratory fashion.
      METHODS: Eleven patients with hepatitis C and detectable viremia were enrolled.
      Four had Child-Pugh (CP) class A cirrhosis, 4 had Child-Pugh class B cirrhosis,
      and 3 were noncirrhotic. After a single oral dose of green tea extract 400 mg
      containing 94% pure EGCG, blood for EGCG levels and safety parameters was
      ascertained at 2, 4, and 10 hours. RESULTS: C(max) and AUC to EGCG overlapped
      among the 3 groups, which suggests that the disposition of EGCG was not
      significantly altered in these patients with cirrhosis. CONCLUSIONS: A single 400
      mg oral dose of EGCG was safe and well tolerated by all of the patients in the
      study. These results provide guidance for the continued investigation of the long
      term safety and antitumor potential of EGCG in cirrhotic patients with HCV.

PMID- 23153662
TI  - Current twin studies in Germany: report on CoSMoS, SOEP, and ChronoS.
AB  - This article summarizes the status of three recent German twin studies: CoSMoS,
      SOEP, and ChronoS. The German twin study on Cognitive Ability, Self-Reported
      Motivation, and School Achievement (CoSMoS) is a three-wave longitudinal study of
      monozygotic and dizygotic twins reared together, and aims to investigate
      predictors of and influences on school performance. In the first wave of the data
      collection in 2005, 408 pairs of twins aged between 7 and 11 as well as their
      parents participated in CoSMoS. The SOEP twin study is an extended twin study,
      which has combined data from monozygotic and dizygotic twins reared together with
      additional data from full sibling pairs, mother-child, and grandparent-child
      dyads who participated in the German Socio-Economic Panel (GSOEP) study. The SOEP
      twin project comprises about 350 twin and 950 non-twin pairs aged between 17 and
      70. Data were collected between 2009 and 2010, with a focus on personality
      traits, wellbeing, education, employment, income, living situation, life
      satisfaction, and several attitudes. The aim of the Chronotype twin study
      (ChronoS) was to examine genetic and environmental influences on chronotype
      (morningness and eveningness), coping strategies, and several aspects of the
      previous SOEP twin project in a sample of 301 twin pairs aged between 19 and 76
      years, recruited in 2010 and 2011. Part of the ChronoS twin sample also
      participated in the earlier SOEP twin study, representing a second wave of
      assessments. We briefly describe the design and contents of these three studies
      as well as selected recent findings.

PMID- 23153663
TI  - Natural history of partial anterior cruciate ligament tears: a systematic
      literature review.
AB  - INTRODUCTION: Partial anterior cruciate ligament (ACL) tear is frequent, and
      indications for surgery may be raised by a diagnostic aspect associating slight
      laxity with no clear pivot-shift. Unlike that of complete ACL tear, the natural
      history of partial tear remains controversial. MATERIAL AND METHOD: A systematic
      literature review searched for referenced publications on the natural history of
      partial ACL tear. Twelve specific articles were retrieved. Initial diagnosis was
      systematically confirmed on arthroscopy, without ACL surgery. The following
      criteria were analyzed: firstly, preoperative: confirmation of inclusion
      criteria, preoperative clinical data, follow-up, arthroscopic lesion assessment,
      Lachman test, Pivot shift test, hemarthrosis, associated lesions and secondly,
      follow-up: Lachman test, Pivot shift test, revision surgery, functional clinical
      scores, pain, sport and return to sport, meniscal events. RESULTS:
      Preoperatively, Lachman tests were positive (soft or delayed) in a mean 49.7% of
      cases (range, 0-100%); pivot shift test was systematically negative. At a mean
      5.2 years' follow-up, Lachman test was "positive" in 47.6% of cases (range, 38
      59%), with positive pivot shift test in 26.3% (range, 5-51%). 54.3% patients
      reported pain (range, 36-64%), and mean Lysholm score was 88.4 (17-100%). Fifty
      two percent (21-60%) of patients resumed sport at their previous level.
      DISCUSSION/CONCLUSION: The natural history of non-operated partial ACL tear is
      good over the medium term, especially if patients limit their sports activities.
      The greater the functional instability, the more frequent is residual pain.
      Laxity, although not quantified, seems to progress with time, with a positive
      pivot shift test emerging in a quarter of cases. Functional management may be
      recommended in non-athletic patients without meniscal lesion, but surgical
      treatment may be recommended in other patients. Indications for ACL
      reconstruction are thus the same in partial as in complete tear.

PMID- 23153664
TI  - Salvage technique for postoperative infection and necrosis of the Achilles
      tendon.
AB  - Surgery of the Achilles tendon is associated with postoperative morbidity related
      to wound healing. Necrotic infection of the tendon is a rare but serious
      complication that may be associated with increasingly invasive surgical
      treatments using various free flap transfers proposed in the literature. Dealing
      with this complication, we prefer the technique of managed wound healing
      suggested by Dautry. The surgical procedure includes radical debridement of the
      infected tissue and necrotic Achilles tendon followed by managed wound healing
      with daily irrigation. Fifteen cases were treated between 1994 and 2003. Healing
      was achieved after 30 to 100 days. MRI results show scar tissue continuity
      suggesting a neotendon formation. Function was very satisfactory in 9/15 ankles.
      The salvage technique presented here for cases of infection and necrosis of the
      Achilles tendon is simple with low morbidity and results in effective wound and
      tendon healing with satisfactory functional and anatomical results.

PMID- 23153665
TI  - Current concept in rotational laxity control and evaluation in ACL
      reconstruction.
AB  - Rotation combined with translation; compose the three-dimensional motion of the
      knee subluxation in anterior cruciate ligament deficient knee. The worldwide
      scientists were focused initially on the translation part of this complex 3D
      motion, but since the beginning of the century there was a large interest on knee
      rotational laxity study. Lot of paper reported new devices and results with an
      explosion since the beginning of the decade. The purpose of this review is to
      provide an extensive critical analysis of the literature and clarify the
      knowledge on this topic. We will start with a dismemberment of different
      rotational laxities reported: the rotation coupled with translation in 2D tests
      such as Lachman test and anterior drawer test; the rotational envelope
      considering the maximum internal external rotation; and the "active rotation"
      occurring in 3D Pivot-shift (PS) test. Then we will analyze the knee kinematics
      and the role of different anterior cruciate ligament (ACL) bundle on rotation. A
      review of different mechanical and radiological devices used to assess the
      different rotations on ACL deficient knees will be presented. Two groups will be
      analyzed, dynamic and static conditions of tests. Navigation will be described
      precisely; it was the starter of this recent interest in rotation studies. Opto
      electronic and electromagnetic navigation systems will be presented and analyzed.
      We will conclude with the last generation of rotational laxity assessment
      devices, using accelerometers, which are very promising.

PMID- 23153666
TI  - The role of fibular fixation in the treatment of tibia diaphysis distal third
      fractures.
AB  - INTRODUCTION: Combined fractures of the distal third of tibia diaphysis and
      fibula diaphysis are a common orthopedic injury. There is an ongoing debate about
      the necessity of fibular fixation when associated to distal third tibial
      fracture. This study aims at evaluating the role of fibular fixation in the
      treatment of distal third tibial fractures. HYPOTHESIS: We hypothesized that
      fixation of the fibula increases the stability of fixation in distal third tibial
      and fibular fractures. MATERIALS AND METHODS: In a randomized clinical trial, 53
      patients with concomitant fractures of tibia and ipsilateral fibula at distal
      third level were recruited in this study during a 23-month period. Patients were
      randomized in two groups: patients with fibular fixation (case group) and without
      fibular fixation (control group). The patients were followed up for at least 6
      months postoperatively. RESULTS: There were seven cases exhibiting malalignment
      on immediate postoperative radiographs. Six of them were in group II (control
      group) and one was in group I (case group) (P=0.084). We didn't find nonunion in
      group I and we found three patients in group II (P=0.141). Infection was one in
      group I and two in group II on gustillo II injuries (P=0.516). CONCLUSION:
      Despite its low count of patients, our study didn't show any advantage to fix the
      fibula fracture associated to distal third of tibia diaphysis fracture. It didn't
      show either an increase of complication after fibula open reduction and internal
      fixation. LEVEL OF EVIDENCE: Level III. Randomized prospective study.

PMID- 23153667
TI  - Arthroscopic repair of subscapularis tears: preliminary data from a prospective
      multicentre study.
AB  - BACKGROUND: Until the introduction of arthroscopic-assisted surgery for rotator
      cuff repair, the frequency of subscapularis tears was underestimated. These tears
      remain challenging to treat even with arthroscopy. The absence of a specific
      classification system has hampered communication about the treatment and outcomes
      of the various types of subscapularis tears. The objective of this prospective
      multicentre study was to validate the relevance of arthroscopic subscapularis
      tendon repair based on an assessment of short-term outcomes according to the
      initial extent of the anatomic lesions. METHODS: A prospective multicentre study
      sponsored by the French Society for Arthroscopy was conducted from March 2010 to
      January 2011 in 208 patients with subscapularis lesions that were either isolated
      or associated with limited anterosuperior tears. The Constant and UCLA scores
      were used to assess clinical outcomes. Anatomic and prognostic results were
      evaluated based on the physical examination, preoperative and postoperative
      imaging study findings, and anatomic lesions. Clinical data were available for
      103 patients after at least 1 year of follow-up and radiological data for 129
      patients after at least 6 months. RESULTS: The preliminary clinical results in
      103 patients with at least 1 year of follow-up showed overall statistically
      significant improvements in the Constant and UCLA scores, with resolution of the
      clinical manifestations. The degree of improvement seemed to increase over time.
      The clinical results varied significantly across patient groups based on a
      classification system distinguishing four lesion types. Postoperative imaging
      studies to assess the anatomic results in all patients with at least 6 months of
      follow-up (n=129) showed tendon healing in 92% of cases but also indicated muscle
      wasting of the upper subscapularis muscle in 18.6% of cases and increased fatty
      degeneration of the muscle belly. DISCUSSION: Our study confirms the good
      clinical and radiological results reported in the literature. Our classification
      system distinguishing four lesion patterns was applicable during the imaging
      workup. The main finding from this classification system was the difference in
      results between Type 2 and Type 3 lesions. The trend towards improvements over
      time requires confirmation by longer-term studies, which will also have to
      establish that the increased wasting of the upper subscapularis muscle and fatty
      degeneration of the muscle belly have no adverse effects.

PMID- 23153668
TI  - Retinal drug delivery using eyedrop preparations of poly-L-lysine-modified
      liposomes.
AB  - The purpose of this study was to develop surface-modified liposomes that enhance
      the efficiency of eye drop drug delivery to the retina. Various molecular weights
      and concentrations of the water-soluble cationic polymer poly-L-lysine (PLL) were
      used to modify the surface of submicronized (100 nm) liposomes. Physicochemical
      properties of surface-modified liposomes were determined in vitro, and the
      efficiency of drug delivery to the retina was investigated in vivo. Using
      coumarin-6 as a model drug and fluorescent marker, we show that liposome surface
      modification by PLL dramatically increased delivery to mouse retina segments
      after eye drop administration. However, when PLL of high molecular weight
      (>30,000) was used at higher concentrations (>0.05%), aggregation of surface
      modified liposomes increased particle size and hampered distribution to inner
      ocular tissues. As a result, the efficiency of drug delivery of these aggregated
      surface-modified liposomes was the same as unmodified liposomes. The optimal
      molecular weight and concentration of PLL in drug-delivering liposomes were
      15,000-30,000 and 0.005%, respectively. Under these conditions, PLL-modified
      liposomes were not cytotoxic in corneal or conjunctival cells. In conclusion,
      surface-modified liposomes have great potential as effective retinal drug
      delivery carriers in eye drop formulations.

PMID- 23153669
TI  - Production of nanoparticles-in-microparticles by a double emulsion method: a
      comprehensive study.
AB  - A method based on a double emulsion system (solid-in-water-in-oil-in-water) has
      been developed for the production of nanoparticles-in-microparticles (NIMs). The
      distribution of nanoparticles within the NIMs was explored using light and
      electron microscopy and through assessment of drug loading and release profiles.
      The extent of nanoparticle entrapment within the NIMs was found to be dependent
      on the state (wet vs. dry) in which the nanoparticles were introduced to the
      formulation. The technique was readily adaptable to produce NIMs of different
      morphologies. It is proposed that NIMs and this method to produce them have broad
      application in drug delivery research. 

PMID- 23153670
TI  - Influence of polymeric microcarriers on the in vivo intranasal uptake of an anti
      migraine drug for brain targeting.
AB  - The objective of this study was to investigate the effect of polymeric
      microcarriers on the in vivo intranasal uptake of an anti-migraine drug for brain
      targeting. Mucoadhesive powder formulations consisted of antimigraine drug,
      zolmitriptan, and chitosans (various molecular weights and types) or
      hydroxypropyl methylcellulose (HPMC). Their suitability for nasal administration
      was evaluated by in vitro and ex vivo mucoadhesion and permeation tests. The
      formulations based on chitosan glutamate (CG) or HPMC were tested in vivo because
      they showed good mucoadhesive properties and altered the permeation rate of the
      drug. The in vivo results from intravenous infusion and nasal aqueous suspension
      of the drug or nasal particulate powders were compared. The plasmatic AUC values
      obtained within 8h following intravenous administration appeared about three
      times higher than those obtained by nasal administration, independent of the
      formulations. Zolmitriptan concentrations in the cerebrospinal fluid obtained
      from nasal and intravenous administrations were, respectively, 30 and 90 times
      lower than the concentrations of the drug in the blood. Thus, nasal
      administration potentiated the central zolmitriptan activity, allowing a
      reduction in the drug peripheral levels, with respect to the intravenous
      administration. Among nasally administered formulations, CG microparticles showed
      the highest efficacy in promoting the central uptake of zolmitriptan within 1h. 

PMID- 23153671
TI  - An antioxidant regenerating system for continuous quenching of free radicals in
      chronic wounds.
AB  - A novel antioxidant regenerating system consisting of cellobiose dehydrogenase
      (CDH), cellobiose, and phenolic antioxidants with potential application for
      continuous quenching of free radical species in chronic wounds was developed.
      This antioxidant regenerating system, continuously quenched in situ produced .NO,
      O(2)(.-) and OH. radicals and the produced oxidized phenolic antioxidants were
      regenerated back to their original parent compounds by CDH using cellobiose as
      electron donor. This system therefore prevented the accumulation of oxidized
      phenolic antioxidants. Interestingly, this study also challenges the relevance of
      using total antioxidant capacities values of plant crude extracts obtained using
      biologically none relevant radical species like (2,2-diphenyl-1-picrylhydrazyl
      (DPPH)), Trolox Equivalent Antioxidant Capacity (TEAC), etc. when applied as
      medicinal remedies. This is because methoxylated phenolic antioxidants like
      sinapic acid, ferulic acid; 2,6-dimethoxyphenol readily donate their electrons to
      these radicals (DPPH, TEAC, etc.), thereby greatly influencing the total
      antioxidant values although this study showed that they are not at all effective
      in quenching O(2)(.-) radicals and again are not the most effective quenchers of
      NO and OH radicals as demonstrated during this study.

PMID- 23153672
TI  - Anaphylaxis: the great challenge.

PMID- 23153675
TI  - Mental time travel: a case for evolutionary continuity.
AB  - In humans, hippocampal activity responds to the imagining of past or future
      events. In rats, hippocampal activity is tied to particular locations in a maze,
      occurs after the animal has been in the maze, and sometimes corresponds to
      locations the animal did not actually visit. This suggests that mental time
      travel has neurophysiological underpinnings that go far back in evolution, and
      may not be, as some (including myself) have claimed, unique to humans.

PMID- 23153673
TI  - The association between skin collagen glucosepane and past progression of
      microvascular and neuropathic complications in type 1 diabetes.
AB  - PURPOSE: We determined the association between novel and acid-labile skin
      collagen-linked advanced glycation endproducts (AGEs) and the progression of
      microvascular and neuropathic complications from baseline to near study closeout
      in the Diabetes Control and Complications Trial (DCCT). METHODS: From a skin
      biopsy obtained near the close of the DCCT, proteolytic collagen digests were
      analyzed by liquid chromatography/mass spectrometry (LC/MS/MS) for glucosepane
      (GSPNE), glyoxal and methylglyoxal hydroimidazolones (G-H1 and MG-H1) and the
      glycation product fructose-lysine (FL) using isotope dilution method. RESULTS:
      GSPNE and MG-H1 correlated with age and diabetes duration (P<0.02), while GSPNE
      and FL correlated with the history of glycemia expressed as mean A1c (P<=0.003).
      Age and duration-adjusted GSPNE and FL levels were lower in intensive (INT) vs.
      conventional (CONV) treatment subjects in the primary prevention DCCT cohort
      (P<0.0001), and FL was lower in INT in the secondary intervention cohort
      (P<0.0001). GSPNE was associated with increased incidence of retinopathy
      progression (odds ratio (OR) / unit increase in GSPNE: 2.5 for 3 step progression
      on the ETDRS scale, P=0.003) and sustained>=3 microaneurysms (MA) (OR=4.8,
      P<0.0001) from DCCT baseline up to the time of the biopsy, and prevalence of
      microalbuminuria or AER>40mg/24h (OR=5.3, P<0.0001), and confirmed clinical
      neuropathy (OR=3.4, P=0.015) at the time of the biopsy. GSPNE adjusted for mean
      A1c remained significant for >=3 MA (P=0.0252) and AER (P=0.0006). The strong
      association of complications with A1c was reduced or eliminated when adjusted for
      GSPNE. CONCLUSIONS: Glucosepane is a novel AGE marker of diabetic complications
      that is robustly associated with nephropathic, retinopathic and neuropathic
      outcomes despite adjustment for A1c, suggesting that it could be one mediator of
      these complications with possible diagnostic implications.

PMID- 23153674
TI  - Accumulation of tissue macrophages and depletion of resident macrophages in the
      diabetic thymus in response to hyperglycemia-induced thymocyte apoptosis.
AB  - AIMS: We investigated the dynamics and morphology of thymus macrophages in
      response to thymus involution caused by hyperglycemia. Thymus is an organ
      affected early and dramatically after the onset of diabetes, losing most of the
      thymocyte populations but diabetes's impact on the components of the thymus
      stroma is largely unknown. METHODS: Rats were injected with streptozotocin and
      thymus weight, body weight, and glycemia were measured at various time points.
      The dynamics and morphology of macrophages in the diabetic thymus were
      investigated by histology, immunohistochemistry, qPCR, electron microscopy and
      flow cytometry. RESULTS: In hyperglycemic animals the involuting thymus is
      gradually infiltrated by tissue macrophages (ED1-positive) and depleted of
      resident macrophages (ED2-positive). While ED1 positive macrophages are scattered
      in both cortex and medulla the ED2 positive ones are limited to the cortex and
      cortico-medullary junction. CD4+CD11b+macrophages also accumulate. The TUNEL
      reaction that detects the degradation of the DNA from apoptotic thymocytes in the
      macrophages is enhanced. The thymic macrophages enlarge and accumulate lipid
      vacuoles and apoptotic bodies. qPCR measurements of the expression of macrophage
      markers showed a persistent increase in the diabetic thymus after the injection
      of streptozotocin. CONCLUSIONS: Thymus involutes rapidly and persistently after
      the onset of hyperglycemia because of the elevated apoptosis in the thymocytes.
      Tissue macrophages accumulate in the thymus and the resident macrophages
      decrease. This results in an overall increase in macrophage activity in the
      diabetic thymus in response to the elevated apoptosis of thymocytes produced by
      hyperglycemia.

PMID- 23153676
TI  - Characterization of hydroxyphenol-terminated alkanethiol self-assembled
      monolayers: interactions with phosphates by chemical force spectrometry.
AB  - Tannins and humic substances, commonly referred to as natural organic matter
      (NOM), constitute an important component of natural water and soil systems. These
      species contain numerous hydroxyl and carboxyl functional groups whose reactivity
      is strongly dependent on both the quantity and location of these moieties on the
      aromatic ring. In the present study, self-assembled monolayers (SAMs) of 4-(12
      mercaptododecyl)benzene-1,2-diol (o-hydroxyphenol-terminated); 5-(12
      mercaptododecyl)benzene-1,3-diol (m-hydroxyphenol-terminated); bis(11
      thioundecyl) hydrogen phosphate (monoprotic phosphate); and 11-thioundecyl
      dihydrogen phosphate (diprotic phosphate) were prepared and characterized using X
      ray photoelectron spectroscopy (XPS), attenuated total reflectance infrared
      spectroscopy (ATR-IR), and water contact angle measurements. The interactions
      between phenolic groups with phosphates were examined as a function of pH using
      the chemical force spectrometry (CFS) technique. The observations are discussed
      in the context of hydrogen bonding and electrostatic repulsion interaction
      between corresponding species. Adhesion force profiles of hydroxyphenol isomers
      interacting with monoprotic phosphate are dominated by ionic H-bonding; however
      the strength of o-hydroxyphenol interactions is significantly higher. The
      difference in location of hydroxyl groups on the interface also results in
      significantly different force-distance profiles for the isomeric hydroxyphenols
      when interacting with diprotic phosphate.

PMID- 23153677
TI  - Surface tension model for surfactant solutions at the critical micelle
      concentration.
AB  - A model for the limiting surface tension of surfactant solutions (surface tension
      at and above the critical micelle concentration, cmc) was developed. This model
      takes advantage of the equilibrium between the surfactant molecules on the
      liquid/vacuum surface and in micelles in the bulk at the cmc. An approximate
      analytical equation for the surface tension at the cmc was obtained. The derived
      equation contains two parameters, which characterize the intermolecular
      interactions in the micelles, and the third parameter, which is the surface area
      per surfactant molecule at the interface. These parameters were calculated using
      a new atomistic modeling approach. The performed calculations of the limiting
      surface tension for four simple surfactants show good agreement with experimental
      data (~30% accuracy). The developed model provides the guidance for design of
      surfactants with low surface tension values.

PMID- 23153678
TI  - Modeling the granule formation mechanism from single drop impact on a powder bed.
AB  - Granule formation from drop impact on a powder bed can occur by either Tunneling
      or Spreading/Crater Formation. The governing regime can be specified by the
      experimentally determined modified Bond number (Bo(g)*), which is a ratio of the
      capillary force to the gravitational force acting on a particle. It was
      hypothesized that Tunneling would occur when the capillary and surface tension
      forces exceeded the weight of a powder aggregate in contact with the drop. To
      confirm this hypothesis, force balances were derived for a drop in contact with a
      single particle and separately for a drop in contact with an aggregate to predict
      when a particle or aggregate will be sucked into the drop. The force ratios
      derived for each case were compared to the Bo(g)* force ratio used in a
      previously published regime map that separates Tunneling from Spreading/Crater
      Formation. The force balance model correctly predicts the trends of the impact of
      powder and liquid properties on the governing regime. However, the single
      particle model does not quantitatively predict the critical Bond number for
      regime change in Tunneling. The aggregate model gave a better prediction of the
      Tunneling boundary than the single particle model, but it still under predicts
      the experimentally determined Tunneling criterion given by the Bond number.
      Potential reasons for this discrepancy are discussed.

PMID- 23153679
TI  - Interaction between oxalic acid and titania in aqueous ethanol dispersions.
AB  - The charging effects resulting from adsorption of oxalic acid and oxalate anions
      on titania (anatase) surfaces in anhydrous or mixed water-ethanol suspensions is
      summarized. The suddenly enhanced electrical conductance with respect to titania
      free solutions has previously been explained in terms of surface-induced
      electrolytic dissociation (SIED) of weak acids. A recently published model has
      previously been found to successfully characterize the complex SIED effect. The
      model is evaluated experimentally by recording the conductance and pH of the
      dispersion and the zeta potential of the particles. The experimental results can
      be condensed to master curves, which reveal the major properties of the systems
      and facilitate further modeling of extensive experimental results. The
      equilibrium and transport properties of solutions and particles were related, but
      different mechanisms was found to be active in each case. The results suggest
      that at least three adsorption equilibria should be considered in order to
      improve the model.

PMID- 23153680
TI  - Adsorption of high ammonium nitrogen from wastewater using a novel ceramic
      adsorbent and the evaluation of the ammonium-adsorbed-ceramic as fertilizer.
AB  - A novel ceramic adsorbent was developed to adsorb ammonium from high
      concentration ammonium contaminated wastewater. Typical gardening cultivation
      mediums in Japan-Kanuma clay and Akadama clay were used to synthesize the ceramic
      adsorbent. Static batch experiments were conducted to investigate the effect of
      various parameters such as contact time, initial ammonium concentration,
      adsorbent dosage, and competing cations during the ammonium adsorption process.
      The results revealed that the Freundlich isotherm model fitted better with the
      adsorption process than the Langmuir model, and the adsorption process was well
      described by pseudo-second-order kinetic model. The maximum nitrogen adsorption
      capacity of the ceramic adsorbent was 75.5 mg g(-1) at an initial NH(4)(+)-N
      concentration of 10,000 mg L(-1), dosage of 20 g L(-1), and contact time of 480
      min. Results demonstrated that the low-cost ceramic adsorbent directly used as
      nitrogen fertilizer was feasible for its high ammonium nitrogen content, nontoxic
      effect on the environment and excellent soil properties.

PMID- 23153681
TI  - Nanoparticle gel electrophoresis: bare charged spheres in polyelectrolyte
      hydrogels.
AB  - Nanoparticle gel electrophoresis has recently emerged as an attractive means of
      separating and characterizing nanoparticles. Consequently, a theory that accounts
      for electroosmotic flow in the gel, and coupling of the nanoparticle and hydrogel
      electrostatics and hydrodynamics, is required, particularly for gels in which the
      mesh size is comparable to or smaller than the particle radii. Here, we present
      an electrokinetic model for charged, spherical colloidal particles undergoing
      electrophoresis in charged (polyelectrolyte) hydrogels: the gel-electrophoresis
      analogue of Henry's theory for electrophoresis in Newtonian electrolytes. We
      compare numerically exact solutions of the model with several independent
      asymptotic approximations, identifying regions in the parameter space where these
      approximations are accurate or break down. As previously assumed in the
      literature, Henry's formula, modified by the addition of a constant
      electroosmotic flow mobility, is accurate only for nanoparticles that are small
      compared to the hydrogel mesh size. We derived an exact analytical solution of
      the full model by judiciously modifying the theory of Allison et al. for
      uncharged gels, drawing on the superposition methodology of Doane et al. to
      account for hydrogel charge. This furnishes accurate and economical mobility
      predictions for the entire parameter space. The present model suggests that
      nanoparticle size separations (with diameters ?40 nm) are optimal at low ionic
      strength, with a gel mesh size that is selected according to the particle
      charging mechanism. For weakly charged particles, optimal size separation is
      achieved when the Brinkman screening length is matched to the mean particle size.

PMID- 23153682
TI  - Approach towards mild depression: shortest way to treat climacteric syndrome?

PMID- 23153683
TI  - Effect of diabetes on endometrial cancer recurrence and survival.
AB  - OBJECTIVE: The purpose of this study was to investigate the influence of diabetes
      mellitus (DM) on cancer stage at diagnosis, cancer recurrence, and survival of
      endometrial cancer (EC) patients and the influence of the treatment of EC on
      glycaemic control, treatment, and complications of DM. METHODS: In this
      retrospective cohort study all 1644 patients with EC newly diagnosed in 2000-2008
      and recorded in the population-based Eindhoven Cancer Registry (ECR) were
      included. In addition, from this total cohort a subcohort was selected for
      additional data collection and analyses, including 193 EC patients with DM and an
      age-matched sample of 195 EC patients without DM. Patients with FIGO stage IV as
      well as non-endometrioid histology were excluded. RESULTS: In the total cohort EC
      patients with DM had a significantly higher age (69 years vs. 64 years), higher
      FIGO stages and more additional comorbidities compared to EC patients without DM.
      The 5-year overall survival rate for EC patients with DM was significantly lower
      than for EC patients without DM (68% vs. 84%). After adjusting for age, stage,
      period of diagnosis, cardiovascular disease, and treatment, this significant
      effect of DM on overall mortality persisted (HR 1.4, 95% CI: 1.0-1.8). Subcohort
      analyses showed that EC patients with DM were diagnosed more often with a higher
      body mass index (BMI) (34 kg/m(2) vs. 30 kg/m(2)) and EC was not significantly
      associated with changes in DM characteristics over time. Although the 5-year
      overall survival rate for EC patients with DM was significantly lower in the
      subcohort, for EC-specific mortality (n=388) no statistically significant effect
      of DM was observed after adjustment for FIGO stage (HR=1.7, 95% CI: 0.7-3.9).
      CONCLUSIONS: EC patients with DM compared to those without had worse patient
      characteristics, a higher FIGO stage, similar recurrence rates and worse overall
      survival.

PMID- 23153684
TI  - A semi-analytical solution for simulating contaminant transport subject to chain
      decay reactions.
AB  - We present a set of new, semi-analytical solutions to simulate three-dimensional
      contaminant transport subject to first-order chain-decay reactions. The aquifer
      is assumed to be areally semi-infinite, but finite in thickness. The analytical
      solution can treat the transformation of contaminants into daughter products,
      leading to decay chains consisting of multiple contaminant species and various
      reaction pathways. The solution in its current form is capable of accounting for
      up to seven species and four decay levels. The complex pathways are represented
      by means of first-order decay and production terms, while branching ratios
      account for decay stoichiometry. Besides advection, dispersion, bio-chemical or
      radioactive decay and daughter product formation, the model also accounts for
      sorption of contaminants on the aquifer solid phase with each species having a
      different retardation factor. First-type contaminant boundary conditions are
      utilized at the source (x=0 m) and can be either constant-in-time for each
      species, or the concentration can be allowed to undergo first-order decay. The
      solutions are obtained by exponential Fourier, Fourier cosine and Laplace
      transforms. Limiting forms of the solutions can be obtained in closed form, but
      we evaluate the general solutions by numerically inverting the analytical
      solutions in exponential Fourier and Laplace transform spaces. Various cases are
      generated and the solutions are verified against the HydroGeoSphere numerical
      model.

PMID- 23153685
TI  - [Somatoform disorders in neurology visits: history and circumstances:
      retrospective study of 124 cases].
AB  - We report 124 cases of somatoform disorders, considering psychogenic disorders at
      the same level as neurological disorders. We noted any psychic, somatic or social
      condition (history taking) and facilitating circumstances. The patients were aged
      16 to 84 years old; 71.7% were women. We observed pain (35.4%), psychogenic
      headache (25%), sensorimotor loss (27.4%), gait and psychogenic tremor (17.7%),
      cognitive disorders (11.8%), ocular symptoms (7.2%), and urogenital symptoms
      (2.4%). Delay to consultation ranged from a few days to 20 years. Psychiatric
      comorbidity was noted in 30.6% of the cases. In 55.6% of 124 cases, we observed a
      psychological background. It was a childhood trauma in 15.3% of these cases. In
      one-third of the 124 situations, we noted an underlying somatic or social
      condition. Facilitation conditions were frequently mixed. Somatic and/or
      psychological conditions were noted in one-third of the 124 cases and social
      conditions in half of them. The neurologist is faced with the challenge of naming
      the symptom (most often labelled a functional disorder) and of making the
      decision to stop or limit investigations. Visits by patients with psychogenic
      disorders make up a significant percentage of neurology speciality appointments.
      The neurologist should not limit the consultation to differentiating "real"
      symptoms from psychogenic somatoform disorders, but should also propose a
      straightforward compassionate approach for effective therapeutic care. By
      carefully listening to the patient's dialogue, the neurologist can help the
      patient give meaning to the symptoms, and progress towards improved well-being.

PMID- 23153686
TI  - [Developments in hereditary neuropathies].
AB  - Hereditary sensorimotor neuropathies, or Charcot-Marie-Tooth disease (CMT)
      comprise a group of diseases with heterogeneous clinical, electrophysiological
      and genetic expression. They are classified by the mode of inheritance (autosomal
      dominant, X-linked dominant, autosomal recessive) and their electrophysiological
      characteristics taking into account the speed of motor conduction of the median
      nerve (demyelinating, intermediary and axonal forms). Certain purely motor forms
      are called spinal CMT or hereditary distal motor neuropathy, or distal spinal
      amyotrophy. CMT involving an important sensorial component, trophic disorders, or
      signs of dysautonomia are included in the classification of hereditary sensory
      and autonomic neuropathies.

PMID- 23153688
TI  - Hypertension caused by primary hyperaldosteronism: increased heart damage and
      cardiovascular risk.
AB  - INTRODUCTION AND OBJECTIVES: Primary hyperaldosteronism is the most common cause
      of secondary hypertension. Elevated aldosterone levels cause heart damage and
      increase cardiovascular morbidity and mortality. Early diagnosis could change the
      course of this entity. The objective of this report was to study the clinical
      characteristics, cardiac damage and cardiovascular risk associated with primary
      hyperaldosteronism. METHODS: We studied 157 patients with this diagnosis. We
      analyzed the reason for etiological investigation, and the routinely performed
      tests, including echocardiography. We used a cohort of 720 essential hypertensive
      patients followed in our unit for comparison. RESULTS: Compared with essential
      hypertensive patients, those with hyperaldosteronism were younger (56.9 [11.7]
      years vs 60 [14.4] years; P<.001), had higher blood pressure prior to the
      etiological diagnosis (136 [20.6] mmHg vs 156 [23.2] mmHg), more frequently had a
      family history of early cardiovascular disease (25.5% vs 2.2%; P<.001), and had a
      higher prevalence of concentric left ventricular hypertrophy (69% vs 25.7%) and
      higher cardiovascular risk. Specific treatment resulted in optimal control of
      systolic and diastolic blood pressures (from 150.7 [23.0] mmHg and 86.15 [14.07]
      mmHg to 12.69 [15.3] mmHg and 76.34 [9.7] mmHg, respectively). We suspected the
      presence of hyperaldosteronism because of resistant hypertension (33.1%),
      hypokalemia (38.2%), and hypertensive crises (12.7%). Only 4.6% of these patients
      had been referred from primary care with a suspected diagnosis of
      hyperaldosteronism. CONCLUSIONS: Hyperaldosteronism should be suspected in cases
      of resistant hypertension, hypokalemia and hypertensive crises. The diagnosis of
      hyperaldosteronism allows better blood pressure control. The most prevalent
      target organ damage is left ventricular hypertrophy.

PMID- 23153689
TI  - Computer-aided detection/diagnosis of breast cancer in mammography and
      ultrasound: a review.
AB  - Breast cancer is the most common form of cancer among women worldwide. Early
      detection of breast cancer can increase treatment options and patients'
      survivability. Mammography is the gold standard for breast imaging and cancer
      detection. However, due to some limitations of this modality such as low
      sensitivity especially in dense breasts, other modalities like ultrasound and
      magnetic resonance imaging are often suggested to achieve additional information.
      Recently, computer-aided detection or diagnosis (CAD) systems have been developed
      to help radiologists in order to increase diagnosis accuracy. Generally, a CAD
      system consists of four stages: (a) preprocessing, (b) segmentation of regions of
      interest, (c) feature extraction and selection, and finally (d) classification.
      This paper presents the approaches which are applied to develop CAD systems on
      mammography and ultrasound images. The performance evaluation metrics of CAD
      systems are also reviewed.

PMID- 23153690
TI  - Reactivity of iron(II)-bound nitrosyl hydride (HNO, nitroxyl) in aqueous
      solution.
AB  - The reactivity of coordinated nitroxyl (HNO) has been explored with the
      [Fe(II)(CN)(5)HNO](3-) complex in aqueous medium, pH 6. We discuss essential
      biorelevant issues as the thermal and photochemical decompositions, the
      reactivity toward HNO dissociation, the electrochemical behavior, and the
      reactions with oxidizing and reducing agents. The spontaneous decomposition in
      the absence of light yielded a two-electron oxidized species, the nitroprusside
      anion, [Fe(II)(CN)(5)NO](2-), and a negligible quantity of N(2)O, with
      k(obs)~5*10(-7)s(-1), at 25.0 degrees C. The value of k(obs) represents an upper
      limit for HNO release, comparable to values reported for other structurally
      related L ligands in the [Fe(II)(CN)(5)L](n-) series. These results reveal that
      the FeN bond is strong, suggesting a significant sigma-pi interaction, as already
      postulated for other HNO-complexes. The [Fe(II)(CN)(5)HNO](3-) ion showed a quasi
      reversible oxidation wave at 0.32 V (vs normal hydrogen electrode), corresponding
      to the [Fe(II)(CN)(5)HNO](3-)/[Fe(II)(CN)(5)NO](3-),H(+) redox couple.
      Hexacyanoferrate(III), methylviologen and the nitroprusside ion have been
      selected as potential oxidants. Only the first reactant achieved a complete
      oxidation process, initiated by a proton-coupled electron transfer reaction at
      the HNO ligand, with nitroprusside as a final oxidation product. Dithionite acted
      as a reductant of [Fe(II)(CN)(5)HNO](3-), in a 4-electron process, giving NH(3).
      The high stability of bound HNO may resemble the properties in related Fe(II)
      centers of redox active enzymes. The very minor release of N(2)O shows that the
      redox conversions may evolve without disruption of the FeN bonds, under
      competitive conditions with the dissociation of HNO.

PMID- 23153691
TI  - A new set of risk equations for predicting long term risk of all-cause mortality
      using cardiovascular risk factors.
AB  - OBJECTIVES: As population ages and treatment for cardiovascular disease improves
      the risk of all-cause mortality has become a more meaningful outcome. We develop
      all-cause mortality equations for predicting long term risk using cardiovascular
      risk factors. METHODS: The 24-year risk of all-cause mortality was evaluated
      using Cox model for participants aged 40-81 years at the 10th or 11th examination
      of the Framingham original cohort and the first examination of the offspring
      cohort-all of whom were free of major chronic diseases. RESULTS: The predictors
      of all-cause mortality were age, sex, systolic blood pressure, total
      cholesterol/HDL ratio and smoking status. Risk prediction improved significantly
      when intensity of smoking and time since quitting were included into smoking
      status. A reduced model based on non-laboratory risk factors also demonstrated
      good predictive performance. CONCLUSIONS: All-cause mortality risk equations
      incorporating cardiovascular risk factors provide an improved tool to quantify
      risk and guide prevention of mortality. There are great potentials for prevention
      of the CVD epidemic and for increased longevity with health, through improved
      life-styles and consequent lower levels of blood pressure, cholesterol and
      smoking.

PMID- 23153692
TI  - Short-term hypoxia increases phosphorylated tyrosine hydroxylase at Ser31 and
      Ser40 in rat carotid body.
AB  - Long-term hypoxia (days to weeks) increases phosphorylation of tyrosine
      hydroxylase (TH) at Ser31 and Ser40 in the carotid body (CB). In the present
      study, we examined the time course of TH phosphorylation at Ser31 and Ser40 in CB
      of rats exposed to short-term hypoxia (within 1 day) for 0-24 h. Using
      immunoblotting, the signal intensities of both phosphorylated TH were more
      intense in CB of rats exposed to hypoxia for 6, 12, 18, and 24h than those of
      controls. Using immunohistochemistry, immunoreactive intensities of both
      phosphorylated TH were significantly more intense in glomus cells after rats were
      exposed to hypoxia for 6, 12, 18, and 24 h than those of controls (p<0.05). These
      results show that phosphorylation of TH at Ser31 and Ser40 is increased in CB
      glomus cells by short-term hypoxia, suggesting that activation of TH via
      phosphorylation contributes to the facilitation of catecholamine biosynthesis in
      CB glomus cells at an early stage of hypoxia.

PMID- 23153693
TI  - Effect of progesterone on respiratory response to moderate hypoxia and apnea
      frequency in developing rats.
AB  - We used whole-body plethysmography and pulse oximetry to assess the effects of
      acute administration of progesterone (4 mg/kg, i.p.) on normoxic ventilation,
      hypoxic ventilatory response (HVR: FiO(2)=12% over 20 min), metabolism, and apnea
      frequency in rats on postnatal (P) days P1, P4, P7, and P12. Arterial oxygen
      saturation was continuously measured, and apneas were discriminated based on the
      degree of associated desaturation, at least 5 units less than the value before
      the desaturation. In normoxia, progesterone did not alter ventilation, metabolism
      or the coefficient of variation of minute ventilation at any age studied when
      compared with the control group (saline). However, it decreased apnea frequency
      and apnea associated with desaturation only in P1 rats. In hypoxia: progesterone
      increased the peak HVR in P4 and P7 rats, increased the steady-state HVR (mean at
      15-20 min of exposure) in P1, P4 and P7 without affecting the rats' metabolic
      rate, decreased the coefficient of variation of minute ventilation in P4 and P7
      rats, and finally, decreased apnea frequency only in the P1 rats with no effect
      on apnea associated with desaturation at any age. We conclude that acute
      administration of progesterone has no effect on baseline ventilation, but it
      increases HVR in rats younger than 7 days, and decreased the frequency of apnea
      only in P1 rats.

PMID- 23153694
TI  - Outgoing editor-in chief.

PMID- 23153695
TI  - Oviparity or viviparity? That is the question....
AB  - The modes of reproduction undoubtedly represent one of the most critical life
      history traits because they profoundly affect fitness and survival. The parent
      offspring conflict over the degree of parental investment may be the main
      selective factor in the evolution of reproduction. Although the modes of sexual
      reproduction are remarkably diversified in animals, the traditional typology
      spanning three classes does not seem to be adequate to clarify the level of
      parental investment. Thus, lecithotrophy does not provide any information on the
      retention of the zygotes inside the parent's body and matrotrophy only indicates
      that nutrients are provided by mother but does not make any distinction between
      various types of maternal care. I here present a scientific typology of the
      reproductive modes comprising five classes: ovuliparity, oviparity, ovo
      viviparity, histotrophic viviparity and hemotrophic viviparity. Based on the
      development stage of the zygote and on its interrelation with the parent, my
      classification details the degree of contrivances by which animals provide
      alternative parental investment in their offspring. Hence, this typology
      possesses a great heuristic value, both in reproduction and evolutionary biology.
      These different modes of reproduction do represent a sequence, with ovuliparity
      being the most primitive and hemotrophic viviparity the most advanced mode.
      Lastly, the comparative analysis of different reproductive modes in vertebrates
      suggests that climatic conditions (cold) could be one of the strongest selection
      pressures for extending egg retention and the establishment of viviparity.

PMID- 23153696
TI  - Advances in understanding the physiological mechanism of maternal immune
      tolerance to the embryo.
AB  - The results of immunological studies, especially research conducted in the last
      decade, have shown that free (not bound to protein) progesterone molecules
      (fP(4)) can block the ability of dendritic cells, monocytes and macrophages to
      present antigens to Th cells and thereby reduce maternal immune activity and
      increase the maternal tolerance to the semiallogenic embryo. Endocrine studies
      have shown that fP(4) in the female reproductive organs are transferred at high
      concentrations into the arterial blood that supplies the oviduct and uterus due
      to the special adaptations of the blood circulation and lymph flow. Here, the
      authors present the results of numerous studies documenting their thesis that an
      important element of maternal tolerance of the semiallogenic embryo in the uterus
      is conditioned by the close interaction of two processes that occur in the
      reproductive organs: (1) the local decrease of maternal immune system activity,
      in which the ability of dendritic cells, macrophages and monocytes to present
      embryonic antigens to Th cells is blocked by fP(4); and (2) the proper function
      of the system governing the local retrograde and destination transfer of
      hormones, which increases the concentration of fP(4) that are able to immediately
      bind to their receptors in dendritic cells and in the monocytes and macrophages
      present in the blood supplying the oviduct and uterus. The authors believe that
      the local interaction of the immune and endocrine systems in the female
      reproductive tract reduces local maternal immunoreactivity and thus fulfils a
      critical physiological role; this mechanism protects the embryo but does not
      change the general immunological resistance of the mother.

PMID- 23153697
TI  - Glutathione-supplemented tris-citric acid extender improves the post-thaw quality
      and in vivo fertility of buffalo (Bubalus bubalis) bull spermatozoa.
AB  - In this study we evaluated the effects of semen extender supplementation with
      different concentrations of glutathione (GSH) on buffalo (Bubalus bubalis) bull
      sperm motility, plasma membrane integrity, viability and DNA integrity as well as
      in vivo fertility. Semen from three Nili-Ravi buffalo bulls was collected, and
      qualified semen ejaculates (n=18) were split into five aliquots for dilution (37
      degrees C; 50*10(6)spermatozoaml(-1)) with experimental tris-citric acid extender
      containing 0, 0.5, 1.0, 1.5 or 2.0 mM GSH. Extended semen was cooled to 4 degrees
      C, equilibrated and filled in French straws. The straws were kept on liquid
      nitrogen vapors (5 cm above the LN(2) level) for 10 min and plunged in liquid
      nitrogen for storage. Sperm motility (%), plasma membrane integrity (%),
      viability (%) and DNA integrity (%) were assessed at 0, 2 and 4h post-thawing (37
      degrees C). Extender supplementation with GSH (0.5, 1.0, 1.5 and 2.0 mM)
      increased sperm motility, plasma membrane integrity and viability in a dose
      dependent manner. Sperm DNA integrity was higher (p<0.05) in all experimental
      extenders containing GSH when compared to the control extender (0 mM GSH). The in
      vivo fertility rate of cryopreserved buffalo bull (n=2) spermatozoa was higher
      (p<0.05) in extender containing 2.0 mM GSH compared to that of control. In
      summary, tris-citric acid extender supplemented with glutathione improved the
      freezability of buffalo bull spermatozoa in a dose dependant manner. Moreover,
      the addition of 2.0 mM GSH to the extender enhanced the in vivo fertility of
      buffalo (Bubalus bubalis) bull spermatozoa.

PMID- 23153698
TI  - The effect of radio electric asymmetric conveyer treatment on sperm parameters of
      subfertile stallions: a pilot study.
AB  - The Radio Electric Asymmetric Conveyer (REAC) has been mostly applied to treat
      symptoms related to psychological stress. In the study, we demonstrated the
      effect of REAC-Veterinary Neuro Psycho Physical Optimization (VNPPO) treatment
      protocol on sperm parameters of subfertile (n=11) and fertile (n=4) stallions.
      Subfertile stallions showed a reduced sperm concentration, progressive motility
      and normal morphology compared to fertile stallions. An increase in progressive
      sperm motility and quality of sperm morphology was found in subfertile stallions
      after the REAC-VNPPO treatment. The positive effect of the REAC-VNPPO treatment
      was visible in a reduced number of reacted or absent acrosomes, nuclei with
      marginated chromatin and presence of cytoplasmic residues. Thus, we suggest that
      the REAC-VNPPO treatment for stallions with idiopathic subfertility may enhance
      the reproductive performance of stallions.

PMID- 23153699
TI  - Effects of quinestrol and levonorgestrel on prolactin serum concentration in
      lactating Mongolian gerbils (Meriones unguiculatus) and reproductive parameters
      of their offspring.
AB  - The effects of the two sterilants, quinestrol (QE) and levonorgestrel (LNG) on
      serum prolactin (PRL) level in lactating Mongolian gerbils and reproductive
      parameters of their offspring were examined in the study. Both sterilants
      increased the serum PRL level in lactating gerbils. The body weight as well as
      weights of the ovary, testis, epididymides, and seminal vesicles were lower,
      whereas that of the uterus was higher in the pups originating from QE-treated
      mothers in comparison to controls. Histological ovarian sections of the offspring
      from QE-treated mothers contained only growing follicles, whereas their uterine
      sections showed a thinner endometrium, thicker myometrium, and greater epithelial
      cell height than in controls. The histometrical testis characteristics as well as
      sperm concentration and motility of male pups from QE-treated mothers were lower
      compared to those of the control group. The serum gonadotropin levels of female
      pups from mothers treated with QE were lower, whereas the serum estradiol (E(2))
      and progesterone (P(4)) levels were higher than in control gerbils. In contrast,
      serum gonadotropin and testosterone (T) levels of male pups from QE-treated
      mothers were lower compared to controls. LNG did not affect the examined
      parameters of the offspring. The offspring from QE-treated mothers was infertile,
      whereas the offspring from LNG-treated mothers was fertile. In summary, QE and
      LNG have a stimulatory effect on PRL level in lactating gerbils. It also appears
      that QE administered via milk to mothers affects reproductive processes of their
      offspring.

PMID- 23153700
TI  - Expression of ghrelin receptor (GHSR-1a) in rat epididymal spermatozoa and the
      effects of its activation.
AB  - In this study we demonstrated the expression of the ghrelin receptor GHSR-1a in
      rat spermatids and epididymal spermatozoa, as well as some effects of ghrelin on
      the spermatozoa in vitro. For the demonstration of GHSR-1a the
      immunocytochemical, immunofluorescence and Western blotting techniques were
      applied using three different types of antibodies. The response of spermatozoa to
      ghrelin was tested in a series of in vitro experiments and their effects were
      evaluated using confocal microscopy and flow cytometry. GHSR-1a protein was found
      as expressed in the Golgi and acrosomes of spermatids and acrosome regions or the
      head cell membrane of epididymal spermatozoa. The GHSR-1a expression in
      spermatozoa was also confirmed by Western blot. No differences were found in
      percentage of spermatozoa showing annexin-V binding and expression of active form
      caspase-3 between control and ghrelin-treated spermatozoa. This result may
      indicate no pro-apoptotic effects of ghrelin neither at 10(-9) nor 10(-6)mol/L
      concentration. Ghrelin (10(-6)mol/L) increased free intracellular calcium ion
      concentration in the rat spermatozoa. Moreover, stimulation with 10(-6)mol/L
      ghrelin increased, while 10(-4)mol/L ghrelin decreased the number of spermatozoa
      showing progressive motility. In conclusion, the expression of the GHSR-1a
      receptor in spermatozoa, as well as ghrelin influences on sperm motility and
      intracellular calcium ion concentration suggest that such biological effects of
      ghrelin may be produced under in vivo conditions.

PMID- 23153701
TI  - Testosterone, gonadotropins and androgen receptor during spermatogenesis of
      Biomphalaria alexandrina snails (Pulmonata: Basommatophora).
AB  - Endocrine regulation of reproductive processes of the snail Biomphalaria
      alexandrina is poorly recognized. Thus, the aims of the study were: (1) to
      acquire histological images of the ovotestis; (2) to determine the hemolymph
      concentrations of testosterone (T) and gonadotropic hormones (luteinizing
      hormone: LH and follicle stimulating hormone: FSH), (3) to demonstrate androgen
      receptor (AR) immunolocalization in the ovotestis, and (4) to show LH and FSH
      protein expression in cerebral ganglia of small (diameter shell: 4-6mm), medium
      (7-11mm) and large (12-16mm) B. alexandrina snails. These three groups
      represented different reproductive stages of the snail. The AR immunoexpression
      was found in the periphery and inside the acini of small (immature) snails as
      well as in spermatocytes, spermatids, Sertoli cells, the interstitial cells and
      the acinus lining epithelium of medium (mature) snails. Low AR immunoexpression
      was demonstrated in the interstitial cells of large (aged) snails. The neurons at
      the periphery of the cerebral ganglia and connective sheath of the ganglia showed
      a positive FSH and LH immunostaining. T concentration in the hemolymph was higher
      in medium snails than in small and large snails. In contrast, LH concentration
      was higher in medium snails than in small and large snails. These data suggests
      that gonadotropins and T play a role in the gonadal development in B.
      alexandrina.

PMID- 23153702
TI  - Caprine endometrial stromal cells modulate the effects of steroid hormones on
      cytokine secretion by endometrial epithelial cells in vitro.
AB  - The main purpose of this study was to examine the effects of 17beta-estradiol
      (E(2)) and progesterone (P(4)) on cytokine secretion by caprine endometrial
      epithelial cells (EEC) in vitro. Epithelial cells grown alone or in co-culture
      with stromal cells (ESC) were treated with E(2) or P(4), or both. Homogeneity of
      the endometrial cell populations was ascertained immunocytochemically. The
      quantities of cytokines secreted in this system were assessed by ELISA and their
      protein expression by Western blot. The exposure of EEC to P(4) alone or in
      combination with E(2) significantly increased the amount of TGF-beta1, TNF-alpha
      and IL-18 secretion, whereas E(2) had no effect on the synthesis of these
      cytokines. When epithelial cells were co-cultured with ESC, the secretion of TGF
      beta1, TNF-alpha and IL-18 by EEC significantly increased compared to that by EEC
      alone. However, the treatment with both steroids decreased the secretion of TNF
      alpha, IL-18 and TGF-beta1 by EEC in the presence of ESC. In contrast to TGF
      beta1, TNF-alpha and IL-18, the secretion of leukemia inhibitory factor (LIF) by
      EEC was not affected by E(2) and/or P(4) either directly or indirectly. The
      present results indicate that the interactions between caprine endometrial
      stromal and epithelial cells can modulate the secretion of TGF-beta1, TNF-alpha
      and IL-18 by EEC exposed to E(2) and/or P(4)in vitro.

PMID- 23153703
TI  - Direct in vitro effect of LH and steroids on leptin gene expression and leptin
      secretion by porcine luteal cells during the mid-luteal phase of the estrous
      cycle.
AB  - Leptin, the product of the ob gene, is implicated in the control of reproductive
      functions in different species. Leptin transcript and protein are present in
      several tissues including adipose tissue and corpus luteum. The regulation of
      leptin mRNA expression and leptin secretion in porcine luteal cells is not clear.
      In this study, we determined leptin and OB-Rb mRNA/protein levels in porcine
      luteal cells during the mid-luteal phase of the estrous cycle (days 10-12) and
      examined, in vitro, the effects of LH, 17-beta estradiol (E(2)) and progesterone
      (P(4)) on leptin gene expression and leptin secretion in those cells. Leptin and
      long form of leptin receptor (OB-Rb) mRNA expressions as well as leptin and OB-Rb
      protein were detected in the luteal cells by real-time PCR and fluorescence
      immunocytochemistry (F-ICC), respectively. Isolated luteal cells, after
      preliminary culture (48 h) were treated with LH (1; 10; 100 ng/ml), E(2) (0.02;
      0.2; 2; 20 ng/ml) and P(4) (20; 100; 200 ng/ml) for 24 h. LH did not induce
      significant changes in leptin mRNA expression in the luteal cells. A higher level
      of leptin transcript was found in the presence of E(2) (0.02 ng/ml) or P(4) (200
      ng/ml). Estradiol (0.2 ng/ml) and P(4) (200 ng/ml) increased leptin secretion by
      luteal cells. Our results indicate that leptin and OB-Rb genes and proteins are
      expressed in porcine luteal cells and suggest that steroid hormones (E(2) and
      P(4)) affect leptin mRNA expression and leptin secretion during the mid-luteal
      phase of the estrous cycle.

PMID- 23153704
TI  - Comparison of the patterns of antral follicular development between hormonally
      synchronized and natural estrous cycles of non-seasonal, polyestrous goats in the
      tropics.
AB  - The effects of estrus synchronization with prostaglandin F(2alpha) (PGF(2alpha))
      and Controlled Internal Drug Release Device (CIDR) on ensuing antral follicular
      development were documented and compared to natural estrous cycles of non
      seasonal tropical goats. Two to six follicular waves were observed, with the
      three-follicular wave pattern being most frequently observed (58%), followed by
      four follicular waves (31.6%) per estrous cycle. There were no significant
      differences (p>0.05) between the PGF(2alpha)- or CIDR-synchronized and natural
      estrous cycles nor between the synchronized and subsequent non-synchronized
      cycles in terms of the time of ovulation, the duration of inter-ovulatory
      intervals, daily numbers of antral follicles >=3mm in diameter, and the number of
      follicular waves per cycle in the goats of the present study.

PMID- 23153705
TI  - A preliminary search for alternatives to albumin as a medium supplement for the
      culture of human sperm.
AB  - Non-animal macromolecules (Select PhytoneTM UF, wheat peptone, dextran 40,
      hydroxyethyl starch and methyl cellulose) as an alternative medium supplement for
      human spermatozoa were compared to bovine serum albumin. Select PhytoneTM UF and
      wheat peptone discolored the medium and smelled like broth, making them unlikely
      to be acceptable for clinical use, whilst the others were colorless and odorless.
      All supplements were effective in the yield of spermatozoa isolated by swim-up
      technique, and maintenance of sperm motility. In summary, there are non-animal
      macromolecules that will support short-term sperm culture.

PMID- 23153706
TI  - Targeting epidermal growth factor receptor/human epidermal growth factor receptor
      2 signalling pathway by a dual receptor tyrosine kinase inhibitor afatinib for
      radiosensitisation in murine bladder carcinoma.
AB  - Given the promising control of bladder cancer achieved by combined
      chemotherapy/radiotherapy with selective transurethral resection, obstacles
      remain to the treatment of unresectable bladder cancer. The aim of this study was
      to determine whether targeting epidermal growth factor receptor (EGFR)/human
      epidermal growth factor receptor 2 (HER2) can radiosensitise a murine bladder
      tumour (MBT-2) cell line. Cell survival, expression of signal proteins and cell
      cycle changes in MBT-2 cells treated in vitro and in vivo with afatinib, an
      irreversible EGFR/HER2 inhibitor, plus radiotherapy were investigated by colony
      formation assay, Western blot assay and flow cytometry, respectively. Ectopic
      xenografts were established by subcutaneous injection of MBT-2 cells in C3H/HeN
      mice. Mice were randomised into 4 groups to receive afatinib (10mg/kg/day on day
      1-7) and/or radiotherapy (15Gy on day 4). Positron emission tomography (PET) on
      day 8 was used to evaluate the early treatment response. Afatinib (200-1000nM)
      increased cell killing by radiation (0-10Gy). Pre-treatment of irradiated cells
      with afatinib inhibited radiation-activated HER2 and EGFR phosphorylation. As
      compared to either treatment alone, the combination increased the level of the
      cleavage form of poly (ADP-ribose) polymerase, the expression of phospho
      gammaH2AX and the percentage of cells in subG1 phase (indicating enhanced
      induction of apoptosis), and decreased tumour metabolism and inhibited tumour
      growth by 64%. Afatinib has therapeutic value as a radiosensitiser of murine
      bladder cancer cells. The synergism between afatinib and radiation likely
      enhances DNA damage, leading to increased cell apoptosis.

PMID- 23153707
TI  - The association between perinatal testosterone concentration and early vocabulary
      development: a prospective cohort study.
AB  - Prenatal exposure to testosterone is known to affect fetal brain maturation and
      later neurocognitive function. However, research on the effects of prenatal
      testosterone exposure has been limited by indirect measures of testosterone and
      small unrepresentative samples. This study investigated whether bioavailable
      testosterone (BioT) concentrations in umbilical cord blood are associated with
      expressive vocabulary development, in a large birth cohort. Cord blood samples
      were taken immediately after delivery and expressive vocabulary was measured at
      two years of age using the language development survey (LDS). BioT concentration
      significantly predicted vocabulary size in males (n=197), such that higher
      concentrations were associated with lower LDS scores, indicating smaller
      vocabulary. This relationship between BioT concentrations and vocabulary at aged
      2 years was not observed in girls (n=176). Higher circulating prenatal
      testosterone concentrations at birth may be associated with reduced vocabulary in
      early childhood among boys.

PMID- 23153708
TI  - Brain-computer interface and semantic classical conditioning of communication in
      paralysis.
AB  - We propose a classical semantic conditioning procedure to allow basic yes-no
      communication in the completely locked-in state as an alternative to instrumental
      operant learning of brain responses, which is the common approach in brain
      computer interface research. More precisely, it was intended to establish
      cortical responses to the trueness of a statement irrespective of the particular
      constituent words and letters or sounds of the words. As unconditioned stimulus
      short aversive stimuli consisting of 1-ms electrical pulses were used. True and
      false statements were presented acoustically and only the true statements were
      immediately followed by electrical stimuli. 15 healthy participants and one
      locked-in ALS patient underwent the experiment. Three different classifiers were
      employed in order to differentiate between the two cortical responses by means of
      electroencephalographic recordings. The offline analysis revealed that semantic
      classical conditioning can be applied successfully to enable basic communication
      using a non-muscular channel.

PMID- 23153709
TI  - Antituberculosis drug-induced hypersensitivity syndrome and its association with
      human leukocyte antigen.
AB  - Antituberculosis drug (ATD)-induced hypersensitivity syndrome (HSS) is a serious
      adverse reaction to ATDs, but much remains to be determined regarding its
      characteristics and genetic risk factors. In this study, we have collected cases
      of ATD-induced HSS and their clinical features, and investigated the associations
      of ATD-induced HSS with human leukocyte antigen (HLA). Subjects with ATD-induced
      HSS and ATD-tolerant controls were recruited through analysis of a multicenter
      adverse drug reaction registry in Korea. HLA allele frequencies were compared
      between subjects with ATD-induced HSS (n = 14) and two control groups: ATD
      tolerant controls (n = 166) and the general population (n = 485). The number of
      enrolled subjects with ATD-induced HSS (n = 14) was comparable to those of
      patients with HSS induced by other common drugs such as allopurinol during the
      recruitment period. The frequency of Cw*0401 was much higher in the cases (50.0%)
      compared with ATD-tolerant controls (12.7%, Pc = 0.0204, OR = 6.90) and the
      general population (12.8%, Pc = 0.0132, OR = 6.82). Our results suggest that ATD
      is an important causative agent inducing HSS with distinct clinical features. The
      strong association of Cw*0401 with the risk for ATD-induced HSS suggests
      immunological involvement in the development of this syndrome.

PMID- 23153710
TI  - Olfactory function in patients with and without temporal lobe resection.
AB  - OBJECTIVES: The study aimed to assess olfactory function in patients with
      temporal lobe epilepsy before and after resection of temporal lobe structures and
      especially addressed the question whether there are any significant olfactory
      differences as a function of side of epileptic focus or resection. MATERIALS AND
      METHODS: Thirteen pre- and 22 postoperative patients and 35 age- and sex-matched
      healthy controls underwent olfactory testing by means of the Sniffin' Sticks
      testing device (comprehensive measurement of threshold, discrimination, and
      identification abilities). RESULTS: Patients with unilateral epileptic focus but
      without temporal lobe resection tended to have impaired identification abilities
      only compared to the healthy controls. There were no significant differences in
      olfactory function on the side of the epileptic focus compared to the non
      affected side. However, the patients after temporal lobe resection presented with
      significantly impaired bilateral discrimination and identification abilities
      compared to the healthy controls and with lower olfactory scores on the side of
      the lesion compared to the non-lesioned side. CONCLUSIONS: Olfactory function is
      only partially impaired preoperatively and will deteriorate further after the
      partial resection on the side of the lesion.

PMID- 23153711
TI  - Validation of a German version of the Neurological Disorders Depression Inventory
      for Epilepsy (NDDI-E).
AB  - INTRODUCTION: Goal of the present study was the validation of a German version of
      the Neurological Disorders Depression Inventory for Epilepsy (NDDI-E). METHODS:
      197 adult epilepsy patients completed the NDDI-E (185 completed both the NDDI-E
      and BDI). 95 patients received psychiatric consults. RESULTS: 33 patients
      received a diagnosis of major depression according to ICD-10 criteria. Internal
      consistency of the NDDI-E was .83. Receiver operating characteristics (ROC)
      showed an area under the curve of 0.92. Applying a cutoff score of >=14 resulted
      in both sensitivity and specificity of 0.85. In the subsample with psychiatric
      consult, at the same optimal cutoff, sensitivity was 0.92, and specificity was
      0.86. Further analyses showed a high concurrent validity with the BDI.
      DISCUSSION: The German version of the NDDI-E constitutes a brief and reliable
      depression screening instrument for epilepsy patients.

PMID- 23153712
TI  - Employment in people with epilepsy from the perspectives of patients,
      neurologists, and the general population.
AB  - OBJECTIVE: Finding and continuing employment are among the most important issues
      for patients with epilepsy (PWE). Earlier studies indicated overrepresentation of
      PWE in manual unskilled or semiskilled positions. METHODS: The questionnaire
      based study was carried out throughout Poland between February and March 2009.
      995 PWE (18-65 yrs), 179 neurologists, and a representative sample of the Polish
      population over 15 yrs of age (1042) were included. RESULTS: 49% of PWE were
      employed. Patients with epilepsy most commonly work as service and sales workers,
      office workers, professionals, and technicians. 56% of Poles, 25% of patients,
      and 28% of neurologists believed that all PWE could work. CONCLUSIONS: Almost 3/4
      of PWE held non-manual positions. This contradicts the stereotype of unskilled
      professions being more suitable for PWE. Generally, Poles have a positive
      attitude towards employment of PWE, but the lack of knowledge about the condition
      makes them less prudent than neurologists and the PWE themselves.

PMID- 23153713
TI  - Early screening and identification of psychological comorbidities in pediatric
      epilepsy is necessary.
AB  - Youth with epilepsy often have co-occurring psychological symptoms that are due
      to underlying brain pathology, seizures, and/or antiepileptic drug side effects.
      The primary study aim was to compare the psychological comorbidities of youth
      with new-onset epilepsy versus chronic epilepsy. Primary caregivers of youth with
      either new-onset (n=82; M(age)=9.9+/-2.9) or chronic epilepsy (n=76;
      M(age)=12.8+/-3.3) completed the Behavioral Assessment Scale for Children-2nd
      Edition. Compared to those with new-onset epilepsy, the chronic group had
      significantly higher depressive and withdrawal symptoms, as well as lower
      activities of daily living. A higher proportion of youth with chronic epilepsy
      exhibited at-risk/clinically elevated depressive symptoms and difficulties with
      activities of daily living compared to the new-onset group. Proactive screening
      in youth with epilepsy to ensure timely identification of psychological symptoms
      and to guide early psychological intervention is warranted.

PMID- 23153715
TI  - Behavioral intervention as an add-on therapy in epilepsy: designing a clinical
      trial.
AB  - Many patients with epilepsy continue to experience seizures despite taking
      medication, and stress is a commonly reported trigger for seizures in these
      individuals. Therefore, a behavioral therapy proven to be effective in epilepsy
      could be a valuable adjunct to current pharmacotherapy. The challenges in testing
      such a behavioral intervention for epilepsy are numerous, including lack of
      consensus about sham designs, maintaining the blind, and powering the study
      absent known effect sizes. Herein, we present the design of a randomized,
      controlled, double-blind trial of progressive muscle relaxation as an add-on
      therapy for refractory epilepsy. Progressive muscle relaxation, which involves
      the tensing and releasing of muscle groups one at a time, is a well-established
      technique that relaxes the body and mind, reduces stress, and may improve seizure
      control. Study design issues discussed may provide insights that will inform
      future behavioral research in epilepsy.

PMID- 23153714
TI  - Ictal dystonia and secondary generalization in temporal lobe seizures: a video
      EEG study.
AB  - The aim of this study was to determine whether the occurrence of unilateral ictal
      limb dystonia (ID) during complex partial seizures (CPS) reduces the possibility
      of contralateral propagation (CP) and secondary generalization (SG) in patients
      with temporal lobe epilepsy (TLE). We assessed 216 seizures recorded in 33
      patients with pharmacoresistant TLE. All patients underwent video-EEG telemetry
      prior to surgical treatment with good postoperative outcomes (Engel I). Ictal
      limb dystonia was observed in 16 of the 33 patients (48%) and 58 of the 216
      seizures (26.8%). We found highly significant differences in the frequency of SG
      between seizures with ID and seizures without ID (2/58 vs. 41/158; 3.45% vs.
      25.95%; p<0.001). Contralateral propagation was seen in 13 of the 57 analyzed
      seizures with ID compared to 85 of the 158 seizures without ID (22.8% vs. 53.8%;
      p<0.001). Among the CPS without SG, we found that the mean duration of seizures
      with ID was significantly longer than the duration of seizures without ID
      (81.66+/-40.10 vs. 68.88+/-25.01 s; p=0.011). Our findings that CP and SG occur
      less often in patients with ID, yet the duration of CPS without SG is longer in
      patients with ID, suggest that the basal ganglia might inhibit propagation to the
      contralateral hemisphere but not ictal activity within the unilateral epileptic
      network.

PMID- 23153716
TI  - The antidepressant sertraline prevents the behavioral and EEG changes induced in
      two animal models of seizures.
AB  - In order to investigate a potential anticonvulsive action of sertraline (i.p.),
      its effects on seizures, EEG epileptiform activity and EEG amplitude increases
      induced by two convulsive agents were evaluated and compared with the effects of
      carbamazepine. Around 20 min following 4-aminopyridine (4-AP, 2.5 mg/kg, i.p.),
      tonic-clonic seizures and epileptiform activity were observed in control animals.
      A single sertraline pre-injection of 2.5 mg/kg, but not of 0.75 mg/kg, prevented
      these changes to 4-AP. Repeated daily administration of 0.75 mg/kg for one week,
      however, effectively inhibited the changes induced by 4-AP. The first generalized
      tonic-clonic seizure and EEG changes in response to pentylenetetrazole (PTZ, 50
      mg/kg, i.p.) were observed near the first minute in control animals. Single
      sertraline doses above 5 mg/kg prevented the PTZ-induced changes. Moreover, a
      single carbamazepine dose of 25 mg/kg (i.p.), but not of 15 mg/kg, prevented the
      changes induced by the above convulsive agents. An anti-seizure action of the
      antidepressant sertraline is strongly suggested by these findings.

PMID- 23153717
TI  - Biperiden for treatment of somnambulism in adolescents and adults with or without
      epilepsy: clinical observations.
AB  - BACKGROUND: Sleepwalking in adolescents and adults may lead to serious injuries
      and require treatment. Anecdotal treatment recommendations include
      benzodiazepines (which also work in focal seizures of the frontal lobe that are
      an important differential diagnosis), imipramine and amitriptyline. METHODS: We
      assessed in a follow-up study of 4 years (medium, range: 2-7 years) the
      usefulness of the antiparkinsonian drug biperiden (Akineton(c)), an acetylcholine
      antagonist with high affinity for muscarinic M1-type receptors, in four
      consecutive cases of arousal disorder with sleepwalking and confusional behavior
      in adolescents and adults with or without epilepsy who did not respond to
      diazepam, clonazepam or amitriptyline. FINDINGS: The adjunctive use of biperiden
      was associated with reduction or remission of sleepwalking episodes in four
      consecutive treatment-refractory cases of arousal disorder with sleepwalking and
      confusional behavior. In contrast, biperiden showed no effect in a patient with
      REM behavioral disorder. INTERPRETATION: Although our observations do not and
      cannot establish the efficacy or safety of biperiden, it may be useful to
      consider biperiden for treatment of sleepwalking, if needed. A putative
      cholinergic mechanism of arousal disorders, including sleepwalking, provides a
      reasonable hypothesis why the anticholinergic agent biperiden might work.
      Evidence for efficacy and safety from randomized controlled trials is needed to
      confirm our preliminary observations.

PMID- 23153718
TI  - Reliability and validity of the Korean version of the Neurological Disorders
      Depression Inventory for Epilepsy (K-NDDI-E).
AB  - The Neurological Disorders Depression Inventory for Epilepsy (NDDI-E) was
      developed as a screening instrument for rapid detection of major depression in
      people with epilepsy (PWE). We evaluated the reliability and validity of the
      Korean version of the NDDI-E (K-NDDI-E) in Korean PWE. This study applied to 121
      outpatients who underwent psychometric tests including the Mini International
      Neuropsychiatric Interview-Plus Version 5.0.0, Beck Depression Inventory-II (BDI
      II), and K-NDDI-E. The K-NDDI-E was easily comprehended and quickly completed by
      the patients. Cronbach's alpha coefficient was 0.898. At a cut off score of 11,
      the K-NDDI-E had a sensitivity of 84.6%, a specificity of 85.3%, a positive
      predictive value of 61.1%, and a negative predictive value of 95.3%. The scores
      of the K-NDDI-E had a positive correlation with those of the BDI-II (p<0.001). In
      conclusion, the K-NDDI-E is a reliable and valid screening tool to detect major
      depression in Korean PWE.

PMID- 23153719
TI  - Signal-averaged and standard electrocardiography in patients with newly diagnosed
      epilepsy.
AB  - Antiepileptic drugs (AEDs) have been associated with cardiac conduction
      abnormalities and arrhythmias, predominantly in patients with predisposing
      cardiac conditions. Ventricular late potentials (VLPs) detected in the signal
      averaged electrocardiogram (SAECG) may imply an increased risk of ventricular
      tachycardia or fibrillation. Twenty-six AED-naive patients with newly diagnosed
      epilepsy and no clinical evidence of heart disease were examined with SAECG and
      standard ECG. Fifteen patients were treated with lamotrigine and ten with
      carbamazepine. No significant abnormality was found in the standard ECG or SAECG
      three to nine months after initiation of AED therapy. In one patient, a VLP was
      detected at baseline and subsequent MRI demonstrated significant right
      ventricular pathology; therefore, this patient was excluded from the rest of the
      study. This exclusion along with only newly diagnosed patients with a low total
      seizure count being included in the study may explain the lack of AED-induced
      electrocardiographic abnormalities in this patient cohort.

PMID- 23153720
TI  - Satisfaction with life domains in people with epilepsy.
AB  - While commonly used quality-of-life instruments assess perceived epilepsy
      associated limitations in life domains and formally document patient concerns,
      less is known of community-dwelling adults with epilepsy about their satisfaction
      with broader life domains, such as satisfaction with housing, education,
      neighborhood, ability to help others, and achievement of goals. The purpose of
      this study was to examine satisfaction with life domains in a representative
      sample of community-dwelling adults with self-reported epilepsy from the 2008
      HealthStyles survey. Following adjustment for sex, age group, race/ethnicity,
      education, and income, people with epilepsy were more likely to report
      frustration in the domains of achievement (e.g., dissatisfaction with education
      and life goals), compromised social interactions (dissatisfaction with family
      life, friends, and social life), and compromised physical capability
      (dissatisfaction with health and energy level). Life satisfaction and other well
      being domains can supplement health indicators to guide treatment and program
      services for people with epilepsy to maximize their well-being.

PMID- 23153721
TI  - Emotion processing bias and age of seizure onset among epilepsy patients with
      depressive symptoms.
AB  - The current study examined whether mood-congruent biases in emotion processing
      extend to epilepsy patients with depressive symptoms and the potentially
      moderating effects of age of seizure onset on these biases. In addition, we
      examined associations between depression (Beck Depression Inventory - 2nd
      Edition; BDI-II) and quality of life (Quality of Life in Epilepsy - 10-item
      questionnaire; QOLIE-10). Data from 101 epilepsy patients were analyzed,
      including 61 females and 40 males. Measures included the Comprehensive Affect
      Testing System - Abbreviated (CATS-A), from which indices of mood-congruent bias
      were derived. A significant interaction between BDI-II raw scores and age of
      seizure onset was found for mood-congruent bias scores in the facial affect
      modality (beta=-0.24, p<.03). Beck Depression Inventory - 2nd Edition raw scores
      were significantly and positively correlated with quality of life (QOLIE-10;
      r=.69, p<.01). Results of the current study show that epilepsy patients with an
      early age of seizure onset may be most at risk for mood-congruent biases when
      experiencing depressive symptoms and that such symptoms have real-world
      implications for quality of life for persons living with epilepsy.

PMID- 23153722
TI  - The Genetics of Sexuality and Aggression (GSA) twin samples in Finland.
AB  - The Genetics of Sexuality and Aggression (GSA) project was launched at the Abo
      Akademi University in Turku, Finland in 2005 and has so far undertaken two major
      population-based data collections involving twins and siblings of twins. To date,
      it consists of about 14,000 individuals (including 1,147 informative monozygotic
      twin pairs, 1,042 informative same-sex dizygotic twin pairs, 741 informative
      opposite-sex dizygotic twin pairs). Participants have been recruited through the
      Central Population Registry of Finland and were 18-49 years of age at the time of
      the data collections. Saliva samples for DNA genotyping (n = 4,278) and
      testosterone analyses (n = 1,168) were collected in 2006. The primary focus of
      the data collections has been on sexuality (both sexual functioning and sexual
      behavior) and aggressive behavior. This paper provides an overview of the data
      collections as well as an outline of the phenotypes and biological data assembled
      within the project. A detailed overview of publications can be found at the
      project's Web site: http://www.cebg.fi/.

PMID- 23153723
TI  - Bias and error in understanding plant invasion impacts.
AB  - Quantitative assessments of alien plant impacts are essential to inform
      management to ensure that resources are prioritized against the most problematic
      species and that restoration targets the worst-affected ecosystem processes.
      Here, we present the first detailed critique of quantitative field studies of
      alien plant impacts and highlight biases in the biogeography and life form of the
      target species, the responses assessed, and the extent to which spatial
      variability is addressed. Observed impacts often fail to translate to ecosystem
      services or evidence of environmental degradation. The absence of overarching
      hypotheses regarding impacts has reduced the consistency of approaches worldwide
      and prevented the development of predictive tools. Future studies must ensure
      that the links between species traits, ecosystem stocks, and ecosystem flows, as
      well as ecosystem services, are explicitly defined.

PMID- 23153724
TI  - Ecological intensification: harnessing ecosystem services for food security.
AB  - Rising demands for agricultural products will increase pressure to further
      intensify crop production, while negative environmental impacts have to be
      minimized. Ecological intensification entails the environmentally friendly
      replacement of anthropogenic inputs and/or enhancement of crop productivity, by
      including regulating and supporting ecosystem services management in agricultural
      practices. Effective ecological intensification requires an understanding of the
      relations between land use at different scales and the community composition of
      ecosystem service-providing organisms above and below ground, and the flow,
      stability, contribution to yield, and management costs of the multiple services
      delivered by these organisms. Research efforts and investments are particularly
      needed to reduce existing yield gaps by integrating context-appropriate bundles
      of ecosystem services into crop production systems.

PMID- 23153725
TI  - Preparation and quality control of silver nanoparticle-antibody conjugate for use
      in electrochemical immunoassays.
AB  - Metal nanoparticle-antibody conjugates are often used as optical or
      electrochemical markers in applications like immunohistochemistry, lateral flow
      tests, biosensors and immunoassays. In order to serve that role, an antibody
      needs to be immobilized on the surface of the nanoparticle. This is easily done,
      as proteins bind to gold and silver nanoparticles spontaneously. However, this
      immobilization process might result in nanoparticle aggregation or the loss of
      the bioactivity of the conjugated antibodies. In this work the optimization of
      antibody immobilization on silver colloid in order to obtain conjugates with the
      best possible activity is investigated. The parameters investigated were the type
      of immobilization buffer, its molarity and pH, the nanoparticle/antibody ratio
      and also blocking and washing protocols to reduce non-specific binding. The
      functionality of the obtained conjugates was tested with electrochemical
      immunoassay. It was found out that the optimum environment for immobilization of
      an anti-myoglobin antibody on silver nanoparticles was 0.2M boric acid pH 6.5
      with 10 MUg of antibody loading per 1 mL of silver colloid. For an anti-troponin
      antibody it was 0.1M boric acid pH 7.5 also with 10 MUg/mL of antibody loading.
      The main problem for silver conjugation was the tendency of silver nanoparticles
      to aggregate during the immobilization process, but by choosing the optimum
      conditions the aggregation problem was completely removed. Here it is
      demonstrated that by using the conjugates prepared with an optimized protocol an
      increase in the sensitivity of the assay 10 times can be achieved. The
      electrochemical immunoassay described here can be used as a test for quality
      control of conjugates and for the estimation of batch-to-batch variability.

PMID- 23153726
TI  - Fungal extracellular ribotoxins as insecticidal agents.
AB  - Fungal ribotoxins were discovered almost 50 years ago as extracellular
      ribonucleases (RNases) with antitumoral properties. However, the biological
      function of these toxic proteins has remained elusive. The discovery of the
      ribotoxin HtA, produced by the invertebrates pathogen Hirsutella thompsonii,
      revived the old proposal that insecticidal activity would be their long searched
      function. Unfortunately, HtA is rather singular among all ribotoxins known in
      terms of sequence and structure similarities. Thus, it was intriguing to answer
      the question of whether HtA is just an exception or, on the contrary, the
      paradigmatic example of the ribotoxins function. The work presented uses HtA and
      alpha-sarcin, the most representative member of the ribotoxins family, to show
      their strong toxic action against insect larvae and cells.

PMID- 23153727
TI  - Some challenges in forensic veterinary pathology: a review.
AB  - Forensic veterinary pathology is a diverse discipline that is in an early phase
      of its development. Common challenges include estimation of the age of skin
      wounds and bruises, the diagnosis of drowning and estimation of the time since
      death. However, many details of the pathological findings related to these
      various aspects await validation. The 'multispecies' nature of veterinary
      pathology, combined with the preponderance of published observations originating
      from animal experimentation, rather than casework, poses two challenges. Firstly,
      extrapolation of results between species may jeopardize the reliability (and
      credibility) of the forensic opinion. Secondly, experimental studies may not
      truly reflect the spectrum of changes seen in actual cases (e.g. extent of
      injuries, infection, age and health of victim). With regard to drowning,
      diagnosis based on post-mortem findings remains problematical. Methods for
      estimation of the time since death (also known as the post-mortem interval)
      continue to be a major focus of study, with fresh avenues such as post-mortem
      diagnostic imaging offering interesting possibilities.

PMID- 23153728
TI  - Prevalence of papillary changes and folliculosis of the palpebral conjunctiva in
      asymptomatic Chinese children.
AB  - PURPOSE: To determine the prevalence of papillary changes of the upper palpebral
      conjunctiva and folliculosis of the lower palpebral conjunctiva in Chinese
      children with no history of contact lens wear. METHOD: Ninety-nine subjects (aged
      6-15 years old) who were interested in a myopia control study were screened for
      papillary changes and folliculosis of the palpebral conjunctiva.
      Photodocumentation was performed under white and blue light (after the
      application of fluorescein) with a yellow filter and the photographs were graded
      by a group of practitioners according to a pre-set grading scale. Analysis was
      performed with the subjects divided into groups according to gender and age.
      RESULTS: More than 48% of the subjects had clinically significant (>=Grade 3)
      papillary changes in the upper palpebral conjunctiva. The prevalence of
      significant folliculosis in the lower lid was about 33%. The prevalence of
      significant papillary changes and folliculosis were similar between genders. No
      differences were observed between younger (age<=10 years old) and older (age>10
      years old) in papillary changes but younger subjects showed a higher prevalence
      of folliculosis. CONCLUSIONS: The prevalences of clinically significant papillary
      changes and folliculosis of unknown aetiology are high in Chinese children.

PMID- 23153729
TI  - Homocysteine imbalance: a pathological metabolic marker.
AB  - Perturbations in methyl group metabolism and homocysteine balance have emerged
      over the past few decades as having defining roles in a number of pathological
      conditions. Numerous nutritional, hormonal, and genetic factors that are
      characterized by elevations in circulating homocysteine concentrations are also
      associated with specific pathological conditions, including cancer development,
      autoimmune diseases, vascular dysfunction, and neurodegenerative disease.
      Although much remains to be explored, our understanding of the relationship
      between disease, methyl balance, and epigenetic control of gene expression has
      steadily progressed. However, homocysteine balance and its role in health and
      disease are not as clearly understood. This review presents our current
      understanding of homocysteine metabolism and its link to specific pathologies.

PMID- 23153730
TI  - A review of calcium supplements and cardiovascular disease risk.
AB  - A group of academic and industry experts in the fields of nutrition, cardiology,
      epidemiology, food science, bone health, and integrative medicine examined the
      data on the relationship between calcium supplement use and risk of
      cardiovascular events, with an emphasis on 4 of the Bradford Hill criteria for
      causal inference: strength, consistency, dose-response, and biological
      plausibility. Results from 2 epidemiological studies and a meta-analysis of
      randomized, controlled clinical trials, including a subgroup analysis from the
      Women's Health Initiative, have prompted concern about a potential association
      between calcium supplement use and a small increase in the risk of adverse
      cardiovascular events. However, a number of issues with the studies, such as
      inadequate compliance with the intervention, use of nontrial calcium supplements,
      potential bias in event ascertainment, and lack of information on and adjustment
      for known cardiovascular risk determinants, suggest that bias and confounding
      cannot be excluded as explanations for the reported associations. Findings from
      other cohort studies also suggest no detrimental effect of calcium from diet or
      supplements, with or without vitamin D, on cardiovascular disease risk. In
      addition, little evidence exists for plausible biological mechanisms to link
      calcium supplement use with adverse cardiovascular outcomes. The authors do not
      believe that the evidence presented to date regarding the hypothesized
      relationship between calcium supplement use and increased cardiovascular disease
      risk is sufficient to warrant a change in the Institute of Medicine
      recommendations, which advocate use of supplements to promote optimal bone health
      in individuals who do not obtain recommended intakes of calcium through dietary
      sources.

PMID- 23153732
TI  - History of zinc in agriculture.
AB  - Zinc was established as essential for green plants in 1926 and for mammals in
      1934. However, >20 y would pass before the first descriptions of zinc
      deficiencies in farm animals appeared. In 1955, it was reported that zinc
      supplementation would cure parakeratosis in swine. In 1958, it was reported that
      zinc deficiency induced poor growth, leg abnormalities, poor feathering, and
      parakeratosis in chicks. In the 1960s, zinc supplementation was found to
      alleviate parakeratosis in grazing cattle and sheep. Within 35 y, it was
      established that nearly one half of the soils in the world may be zinc deficient,
      causing decreased plant zinc content and production that can be prevented by zinc
      fertilization. In many of these areas, zinc deficiency is prevented in grazing
      livestock by zinc fertilization of pastures or by providing salt licks. For
      livestock under more defined conditions, such as poultry, swine, and dairy and
      finishing cattle, feeds are easily supplemented with zinc salts to prevent
      deficiency. Today, the causes and consequences of zinc deficiency and methods and
      effects of overcoming the deficiency are well established for agriculture. The
      history of zinc in agriculture is an outstanding demonstration of the translation
      of research into practical application.

PMID- 23153731
TI  - A historical review of progress in the assessment of dietary zinc intake as an
      indicator of population zinc status.
AB  - Dietary components influencing zinc (Zn) bioavailability were implicated in the
      first cases of human Zn deficiency in the Middle East in the 1960s. It was not
      until the 1980s that isotope tracer studies in humans quantified the effects of
      the type and/or quantity of Zn, protein, iron, and phytate (myo-inositol
      hexaphosphate) on Zn absorption in humans and confirmed the dose-dependent
      inhibitory effect of phytate on Zn absorption. This led to further analysis of
      the Zn and phytate content of foods. The use of phytate-to-Zn molar ratios as
      likely estimates of absorbable dietary Zn followed together with an assessment of
      their relationship with Zn biomarkers in low-income countries (LIC). In the
      1990s, increasing knowledge of factors governing Zn-absorption diets led to
      refinements of Zn requirements and algorithms to estimate dietary Zn
      bioavailability. Their use highlighted that inadequate Zn intake from plant-based
      diets were a major etiological factor in morbidity and stunting in LIC, prompting
      the need to identify indicators of the population's Zn status. Major advances in
      analyses of dietary data pioneered by Beaton in 1980s led to the endorsement in
      2007 of a dietary Zn indicator based on the prevalence of the population with
      usual Zn intake below the estimated average requirement for Zn. Risk of Zn
      deficiency is a public health concern when the prevalence of inadequate Zn intake
      is >25%. Recent findings that Zn bioavailability from high-phytate, whole-day
      diets is lower than previous estimates suggest that revision of Zn estimated
      average requirement for LIC may be warranted.

PMID- 23153733
TI  - Scaling up of breastfeeding promotion programs in low- and middle-income
      countries: the "breastfeeding gear" model.
AB  - Breastfeeding (BF) promotion is one of the most cost-effective interventions to
      advance mother-child health. Evidence-based frameworks and models to promote the
      effective scale up and sustainability of BF programs are still lacking. A
      systematic review of peer-reviewed and gray literature reports was conducted to
      identify key barriers and facilitators for scale up of BF programs in low- and
      middle-income countries. The review identified BF programs located in 28
      countries in Africa, Latin America and the Caribbean, and Asia. Study designs
      included case studies, qualitative studies, and observational quantitative
      studies. Only 1 randomized, controlled trial was identified. A total of 22
      enabling factors and 15 barriers were mapped into a scale-up framework termed
      "AIDED" that was used to build the parsimonious breastfeeding gear model (BFGM).
      Analogous to a well-oiled engine, the BFGM indicates the need for several key
      "gears" to be working in synchrony and coordination. Evidence-based advocacy is
      needed to generate the necessary political will to enact legislation and policies
      to protect, promote, and support BF at the hospital and community levels. This
      political-policy axis in turn drives the resources needed to support workforce
      development, program delivery, and promotion. Research and evaluation are needed
      to sustain the decentralized program coordination "gear" required for goal
      setting and system feedback. The BFGM helps explain the different levels of
      performance in national BF outcomes in Mexico and Brazil. Empirical research is
      recommended to further test the usefulness of the AIDED framework and BFGM for
      global scaling up of BF programs.

PMID- 23153735
TI  - Nutritional translation blended with food science: 21st century applications.
AB  - This paper, based on the symposium "Real-World Nutritional Translation Blended
      With Food Science," describes how an integrated "farm-to-cell" approach would
      create the framework necessary to address pressing public health issues. The
      paper describes current research that examines chemical reactions that may
      influence food flavor (and ultimately food consumption) and posits how these
      reactions can be used in health promotion; it explains how mechanical engineering
      and computer modeling can study digestive processes and provide better
      understanding of how physical properties of food influence nutrient
      bioavailability and posits how this research can also be used in the fight
      against obesity and diabetes; and it illustrates how an interdisciplinary
      scientific collaboration led to the development of a novel functional food that
      may be used clinically in the prevention and treatment of prostate cancer.

PMID- 23153736
TI  - Potassium.

PMID- 23153734
TI  - The role of B vitamins in preventing and treating cognitive impairment and
      decline.
AB  - Many epidemiologic studies have considered whether markers of B-vitamin status
      are associated with cognitive function and cognitive decline. This avenue of
      research was sparked by the homocysteine (Hcy) theory of cardiovascular disease,
      which was extended to Alzheimer's disease when a link between vascular dementia
      and Alzheimer's disease was discovered. Hcy could cause cognitive impairment via
      direct neurotoxicity. However, decreased remethylation of Hcy to methionine might
      also compromise cognitive function by means other than mere Hcy lowering. Folate
      and vitamin B-12 participate in Hcy remethylation and largely determine Hcy
      status. Consequently, much of the relevant research has focused on these 2 B
      vitamins. The many subtly different hypotheses that investigators have addressed
      by attempting to link several B-vitamin status indicators to diverse cognition
      related outcomes have created a confusing body of conflicting studies that seems
      to defy summarization. Nevertheless, themes are discernible that aid
      interpretation, foster hypothesis generation, and inform future study design. For
      example, despite a shared metabolic pathway, Hcy, vitamin B-12, and folate are
      differently related to specific cognitive outcomes. Although consistency of
      findings across studies is often touted as essential to distinguishing causal
      from coincidental relationships, discrepancies among study findings can be even
      more informative.

PMID- 23153737
TI  - Vitamin/trace mineral supplements for the elderly.
AB  - The fraction of population that is elderly has been increasing, as has the
      consumption of vitamin/trace mineral supplements, which is now a multibillion
      dollar industry. Yet the rationale for such supplement intake by the majority may
      be questioned. Some of the current recommendations for micronutrient intake by
      the elderly are extrapolations from recommendations made for younger adults,
      whereas other recommendations are based on measurements of biochemical indices
      not proven to reflect a deficient level in the elderly. Suggestions that the
      elderly need more than the recommended daily allowances largely rest on the
      assumption that they should have biochemical indices similar to younger adults
      despite decreased energy intake with decreased physical and metabolic activities
      of the elderly. Although some individuals require supplementation because of
      problems with intake, absorption, or metabolism, there is little or no proof that
      boosting micronutrient intake above what can be achieved in well-balanced diets,
      some of which already contain fortified foods, will lead to a healthier outcome
      for most elderly individuals. There is not only the potential for unnecessary and
      occasionally harmful excess administered to some, but there is a cost that now
      runs in the billions of dollars and adds to the costs of covering multiple
      chronic disease conditions. Hence, some caution should be exercised in public
      health promulgations concerning routine use of supplements for those in this age
      group (>65 y of age) and of both sexes until more research establishes clear
      connections between the need for micronutrients and nutrient-related health in
      the elderly.

PMID- 23153738
TI  - Food and Nutrition Service, U.S. Department of Agriculture. Building a healthy
      America: A profile of the supplemental nutrition assistance program. April 2012.

PMID- 23153740
TI  - Strategic global approaches to improve breastfeeding rates.

PMID- 23153739
TI  - Clinical nutrition update 2012.

PMID- 23153742
TI  - Oral resveratrol and calcium fructoborate supplementation in subjects with stable
      angina pectoris: effects on lipid profiles, inflammation markers, and quality of
      life.
AB  - OBJECTIVE: This study aimed to evaluate the effects of short-term (60-d) oral
      supplementation with calcium fructoborate, resveratrol, and their combination on
      the clinical and biological statuses of subjects with stable angina pectoris.
      METHODS: A randomized, double-blinded, active-controlled, parallel clinical trial
      was conducted in three groups of subjects. Of the total number of subjects
      included in study (n = 166), 87 completed the 60-d test treatment study period
      and 29 followed in parallel their usual medical care and treatment. The primary
      outcomes were inflammation biomarkers (high-sensitivity C-reactive protein), left
      ventricular function markers (N-terminal prohormone of brain natriuretic
      peptide), and lipid markers (total cholesterol, low-density lipoprotein
      cholesterol, high-density lipoprotein cholesterol, and triacylglycerols). Quality
      of life was assessed by the Canadian Cardiovascular Society angina class and the
      number of angina attacks per week. RESULTS: There was a significant decrease of
      high-sensitivity C-reactive protein in all groups at the 30-d and 60-d visits.
      This decrease was greater (39.7% at 60 d) for group 3 (calcium fructoborate),
      followed by group 2 (resveratrol plus calcium fructoborate, 30.3% at 60 d). The N
      terminal prohormone of brain natriuretic peptide was significantly lowered by
      resveratrol (group 1, 59.7% at 60 d) and by calcium fructoborate (group 3, 52.6%
      at 60 d). However, their combination (group 2) was the most effective and induced
      a decrease of 65.5%. Lipid markers showed slight changes from baseline in all
      groups. The improvement in the quality of life was best observed for subjects who
      received the resveratrol and calcium fructoborate mixture (group 2). CONCLUSION:
      The results indicate that the combination of resveratrol and calcium fructoborate
      has beneficial effects in patients with angina

PMID- 23153743
TI  - Dynamic sentinel lymph node biopsy in patients with invasive squamous cell
      carcinoma of the penis: a prospective study of the long-term outcome of 500
      inguinal basins assessed at a single institution.
AB  - BACKGROUND: Dynamic sentinel node biopsy (DSNB) in combination with ultrasound
      scan (USS) has been the technique of choice at our centre since 2004 for the
      assessment of nonpalpable inguinal lymph nodes (cN0) in patients with squamous
      cell carcinoma of the penis (SCCp). Sensitivity and false-negative rates may vary
      depending on whether results are reported per patient or per node basin, and with
      or without USS. OBJECTIVE: To determine the long-term outcome of patients
      undergoing DSNB and USS-guided fine-needle aspiration cytology (FNAC) in our
      cohort of newly diagnosed cN0 SCCp patients, as well as to analyse any variation
      in sensitivity of the procedure. DESIGN, SETTING, AND PARTICIPANTS: A series of
      consecutive patients with newly diagnosed SCCp, over a 6-yr period (2004-2010),
      were analysed prospectively with a minimum follow-up period of 21 mo. All
      patients had definitive histology of >= T1G2 and nonpalpable nodes in one or both
      inguinal basins. Patients with persistent or untreated local disease were
      excluded from the study. INTERVENTION: All eligible patients had DSNB and USS
      with or without FNAC of cN0 groins. OUTCOME MEASUREMENTS AND STATISTICAL
      ANALYSIS: The primary end point was no nodal disease recurrence on follow-up. The
      secondary end point was complications after DSNB. Sensitivity of the procedure
      was calculated per node basin, per patient, with DSNB alone, and with USS with
      DSNB combined. RESULTS AND LIMITATIONS: Five hundred inguinal basins in 264
      patients underwent USS with or without FNAC and DSNB. Seventy-three positive
      inguinal basins (14.6%) in 59 patients (22.3%) were identified. Four inguinal
      basins in four patients were confirmed false negative at 5, 8, 12, and 18 mo. Two
      inguinal basins had positive USS and FNAC and negative DSNB results. Sensitivity
      of DSNB with USS, with and without FNAC, per inguinal basin was 95% and per
      patient was 94%. Sensitivity of DSNB alone per inguinal basin and per patient was
      92% and 91%, respectively. The DSNB morbidity rate was 7.6%. CONCLUSIONS: DSNB in
      combination with USS has excellent performance characteristics to stage patients
      with cN0 SCCp, with a 5% false-negative rate per node basin and a 6% false
      negative rate per patient.

PMID- 23153744
TI  - Re: Steven Joniau, Laura Van den Bergh, Evelyne Lerut, et al. Mapping of pelvic
      lymph node metastases in prostate cancer. Eur Urol. In press.
      http://dx.doi.org/10.1016/j.eururo.2012.06.057.

PMID- 23153746
TI  - Imaging evaluation of the parapharyngeal space.
AB  - The authors present imaging anatomy of the parapharyngeal space. Imaging approach
      is discussed in terms of the effect it has on differential diagnosis and
      diagnosis by the otolaryngologist. Neoplastic and congenital lesions are
      discussed along with other neck diseases occurring in this space.

PMID- 23153745
TI  - Imaging anatomy of deep neck spaces.
AB  - This article presents a comprehensive analysis of the neck fascia and neck spaces
      that are formed by the interplay of the different fascial layers. Because a solid
      and thorough understanding of the anatomy and relationship of the various neck
      spaces is so valuable in diagnosing and treating diseases of the neck, this
      information organizes the anatomic areas of the neck beginning with and overview,
      followed by extent, anatomic relationship, and contents. Detailed enhanced
      computed tomography images display the anatomic areas of the neck.

PMID- 23153747
TI  - Masticator space: imaging anatomy for diagnosis.
AB  - Masticator space anatomy and pathologic conditions are illustrated examples from
      computed tomography and magnetic resonance imaging. Characteristic imaging
      features of various disease processes are presented to aid the otolaryngologist
      (head and neck surgeon) in diagnosis. The article describes infection, primary
      neoplasm, metastatic disease, Osteonecrosis, and vascular anomalies.

PMID- 23153748
TI  - Parotid space: anatomic imaging.
AB  - The authors present imaging anatomy of the parotid space and discuss non
      neoplastic lesions, autoimmune disorders, cysts, neoplastic lesions, epithelial
      tumors, and nonepithelial lesions. They describe the diseases and their
      appearance on imaging, describing how the differential diagnoses appear, along
      with presenting examples of the images, primarily computed tomography and
      magnetic resonance imaging.

PMID- 23153749
TI  - Imaging of the carotid space.
AB  - The most common of the lesions in the carotid space are discussed in relation to
      their radiographic diagnosis and clinical implications. The appearance of tumors
      and lesions on computed tomography or magnetic resonance imaging is presented,
      and their differential diagnosis is discussed. The image of each carotid disease
      is presented, and the discussion concludes with treatment recommendations and
      considerations.

PMID- 23153750
TI  - Retropharyngeal and prevertebral spaces: anatomic imaging and diagnosis.
AB  - Cross-sectional imaging plays an important role in the evaluation of the
      retropharyngeal space (RPS) and the prevertebral space (PVS). Because of their
      deep location within the neck, lesions arising within these spaces are difficult,
      if not impossible, to evaluate on clinical examination. This article details the
      cross-sectional anatomy and imaging appearances of primary and secondary diseases
      involving the RPS and PVS, including metastasis and spread from adjacent spaces.
      The role of image-guided biopsy is also discussed.

PMID- 23153751
TI  - Submandibular and sublingual spaces: diagnostic imaging and evaluation.
AB  - The mylohyoid muscle divides the lower part of the oral cavity into 2 spaces: the
      sublingual space, which is located superior to the muscle, and the submandibular
      space, inferior to the muscle but superior to the hyoid bone. Although the
      submandibular and sublingual spaces are small, a wide range of pathologic
      processes may involve these spaces. They include cystic lesions, inflammatory
      conditions with various causes, rare vascular lesions, and benign and malignant
      neoplasms. This article outlines the radiologic anatomy of the region, describes
      the various pathologic processes that may affect it, and discusses the use of
      imaging in their evaluation.

PMID- 23153752
TI  - Larynx: anatomic imaging for diagnosis and management.
AB  - Imaging with CT, MRI, or fluorodeoxyglucose F 18-positron emission tomography is
      often an important complement to laryngoscopy for diagnosis and management of
      laryngeal pathology. At most centers, CT is the most popular modality for general
      laryngeal imaging given its widespread availability, ease of acquisition, and
      familiarity to clinicians, whereas MRI and positron emission tomography are used
      as problem-solving tools. Frequent indications for laryngeal imaging include
      cancer staging, suspected submucosal abnormalities, vocal cord paralysis,
      laryngeal trauma, and laryngotracheal stenosis. This article reviews the primary
      imaging modalities used for evaluation of, normal cross-sectional anatomy of, and
      radiologic features of common diseases of the larynx.

PMID- 23153753
TI  - Cervical lymph node evaluation and diagnosis.
AB  - This article discusses the rationale for imaging cervical lymph nodes and reviews
      nodal anatomy and common drainage patterns, imaging features of pathologic lymph
      nodes, and the advantages of various imaging modalities available for evaluation
      and diagnosis of the lymph nodes.

PMID- 23153754
TI  - Lesions of the skull base: imaging for diagnosis and treatment.
AB  - This article provides a summary of how to approach the imaging analysis of
      lesions of the anterior, central, and posterior skull base. The primary focus is
      tumors and tumor-mimickers, and representative examples are shown to
      differentiate the features of lesions that can occur in the same location.

PMID- 23153755
TI  - Postoperative and postradiation changes on imaging.
AB  - The normal appearance of the posttherapy neck after common surgical procedures
      and chemoradiation therapy is presented, with specific details for each surgical
      procedure. Subsequently, the authors emphasize the recognition of complications
      and disease recurrence with illustrated examples.

PMID- 23153756
TI  - Interventional neuroradiology applications in otolaryngology, head and neck
      surgery.
AB  - A review of the current clinical applications of a variety of percutaneous and
      endovascular interventional procedures of the extracranial head and neck is
      presented. After a description of general principles and embolic agents for
      interventional procedures, management of specific disorders is presented and
      procedural steps are described for epistaxis, embolization of vascular head and
      neck tumors, high-flow and low-flow cervical vascular malformations, head and
      neck trauma and bleeding, radiofrequency ablation and cryoablation of tumors,
      along with percutaneous biopsy within the head and neck.

PMID- 23153757
TI  - Otolaryngology and radiology: partners in diagnosing and managing head and neck
      disease.

PMID- 23153758
TI  - Bilateral vision loss responsive to corticosteroids.
AB  - A 48-year-old woman presented with painless bilateral vision loss that began in
      the left eye and responded to steroids, followed by vision loss in the right eye
      one day after completing her steroid taper. Diagnosis was complicated by a
      positive screening test for Leber hereditary optic neuropathy and a negative
      workup for demyelinating disease. Steroid-dependent optic neuropathies such as
      autoimmune optic neuropathy and chronic relapsing inflammatory optic neuropathy
      were considered in the differential. Seven months after initial presentation, the
      patient developed a new periventricular white matter lesion, lesions on her
      cervical and thoracic spinal cord, bilateral leg weakness, and sensory loss
      consistent with multiple sclerosis. 

PMID- 23153759
TI  - Count sir Luigi Preziosi and his glaucoma operation: the development of early
      glaucoma filtering surgery.
AB  - Count Sir Luigi Preziosi (1888-1965) was a famous ophthalmologist from the island
      Republic of Malta. He received his ophthalmic training in Rome and the United
      Kingdom. He practiced ophthalmology in Malta for 45 years and was a professor at
      the University of Malta. Like many physicians in Malta, he was active in the
      politics and governance of his country, serving as president of the Senate,
      president of the National Congress to draft a new constitution, and, finally, as
      president of the National Assembly of Malta. His most important ophthalmologic
      contribution was the development of the thermal sclerostomy filtering operation
      for glaucoma, which he first described in 1924. He referred to this operation
      initially as electro-cautery puncture and later simply as Preziosi's operation.
      Many surgeons considered this procedure an advance over the other available
      filtering operations such as sclerectomy, iridencleisis, and trephination. The
      operation was then further developed in 1957 by Harold G. Scheie of the
      University of Pennsylvania. Scheie referred to his procedure as peripheral
      iridectomy with scleral cautery, and it was a standard filtering operation for
      glaucoma for many years until the development of trabeculectomy.

PMID- 23153760
TI  - Characterizing the antitumor response in mice treated with antigen-loaded
      polyanhydride microparticles.
AB  - Delivery of vaccine antigens with an appropriate adjuvant can trigger potential
      immune responses against cancer leading to reduced tumor growth and improved
      survival. In this study, various formulations of a bioerodible amphiphilic
      polyanhydride copolymer based on 1,8-bis(p-carboxyphenoxy)-3,6-dioxaoctane
      (CPTEG) and 1,6-bis(p-carboxyphenoxy) hexane (CPH) with inherent adjuvant
      properties were evaluated for antigen-loading properties, immunogenicity and
      antitumor activity. Mice were vaccinated with 50:50 CPTEG:CPH microparticles
      encapsulating a model tumor antigen, ovalbumin (OVA), in combination with the
      Toll-like receptor-9 agonist, CpG oligonucleotide 1826 (CpG ODN). Mice treated
      with OVA-encapsulated CPTEG:CPH particles elicited the highest CD8(+) T cell
      responses on days 14 and 20 when compared to other treatment groups. This
      treatment group also displayed the most delayed tumor progression and the most
      extended survival times. Particles encapsulating OVA and CpG ODN generated the
      highest anti-OVA IgG(1) antibody responses in mice but these mice did not show
      significant tumor protection. These results suggest that antigen-loaded CPTEG:CPH
      microparticles can stimulate antigen-specific cellular responses and could
      therefore potentially be used to promote antitumor responses in cancer patients.

PMID- 23153761
TI  - The effects of interactive mechanical and biochemical niche signaling on
      osteogenic differentiation of adipose-derived stem cells using combinatorial
      hydrogels.
AB  - Stem cells reside in a multi-factorial environment containing biochemical and
      mechanical signals. Changing biochemical signals in most scaffolds often leads to
      simultaneous changes in mechanical properties, which makes it difficult to
      elucidate the complex interplay between niche cues. Combinatorial studies on cell
      material interactions have emerged as a tool to facilitate analyses of stem cell
      responses to various niche cues, but most studies to date have been performed on
      two-dimensional environments. Here we developed three-dimensional combinatorial
      hydrogels with independent control of biochemical and mechanical properties to
      facilitate analysis of interactive biochemical and mechanical signaling on
      adipose-derived stem cell osteogenesis in three dimensions. Our results suggest
      that scaffold biochemical and mechanical signals synergize only at specific
      combinations to promote bone differentiation. Leading compositions were
      identified to have intermediate stiffness (~55kPa) and low concentration of
      fibronectin (10MUg ml(-1)), which led to an increase in osteocalcin gene
      expression of over 130-fold. Our results suggest that scaffolds with
      independently tunable niche cues could provide a powerful tool for conducting
      mechanistic studies to decipher how complex niche cues regulate stem cell fate in
      three dimensions, and facilitate rapid identification of optimal niche cues that
      promote desirable cellular processes or tissue regeneration.

PMID- 23153762
TI  - Synergistic antivirus effect of combined administration of Combivir with Angelica
      polysaccharide sulfate.
AB  - This study is to investigate the synergistic effect of Anglica polysaccharide
      sulfate (APS-1) and Combivir, an anti-AIDS drug, on murine leukemia virus in
      vivo. As the results shown, the virus replication was significantly decreased by
      the combination of APS-1 and Combivir, which tended to be further decreased (58%
      inhibition) when compared with that of Combivir alone (51% inhibition).
      Furthermore, both the percentage of CD4(+) cells and CD4(+)/CD8(+) ratio in
      peripheral blood cells were significantly enhanced by this combined
      administration, while the CD4(+) cells was only slightly increased and
      CD4(+)/CD8(+) ratio was not affected by Combivir alone. Additionally, combination
      of APS-1 and Combivir also alleviated the toxicity of Combivir. APS-1 not only
      increased the survival rate of mice administered with LD(50) dose of Combivir,
      but also reduced the hematologic toxicity induced by Combivir, RBC, HGB and PLT
      were restored to normal level. These results suggest that APS-1 had synergistic
      effect with Combivir, which provided new insight into the potential clinical use
      of polysaccharide sulfate in anti-AIDS field.

PMID- 23153763
TI  - Probing the molecular determinant of the lipase-specific foldase Lif26 for the
      interaction with its cognate Lip26.
AB  - As a steric chaperone, the lipase-specific foldase Lif26 from Acinetobacter sp.
      XMZ-26 is required for correct folding of the lipase Lip26 in in vivo co
      expression and in vitro refolding systems. Lif26 interacts with Lip26 as
      determined by yeast two hybrid assays in vivo and GST pull-down experiments in
      vitro. To study the molecular determinants of the interaction between Lif26 and
      Lip26, a homology model-based screening of residues, molecular dynamics (MD)
      simulation-based calculation of interaction energies, and site-directed
      mutagenesis to alter individual screened residues were applied. One conserved
      amino acid in the C-terminal mini-domain of Lif26, Arg332, was involved in the
      interaction with Lip26. Arg332 could not be replaced by any other residue, based
      on saturated site-directed mutagenesis, and it formed a conserved and stable salt
      bridge with Glu112 of Lip26, which may contribute to binding specificity. The
      residues surrounding Arg332, such as Trp288 in alpha9, likely stabilized Arg332
      in the proper conformation for the interaction with Lip26.

PMID- 23153764
TI  - Modelling (18)O2 and (16)O2 unidirectional fluxes in plants. III: fitting of
      experimental data by a simple model.
AB  - Photosynthetic assimilation of CO2 in plants results in the balance between the
      photochemical energy developed by light in chloroplasts, and the consumption of
      that energy by the oxygenation processes, mainly the photorespiration in C3
      plants. The analysis of classical biological models shows the difficulties to
      bring to fore the oxygenation rate due to the photorespiration pathway. As for
      other parameters, the most important key point is the estimation of the electron
      transport rate (ETR or J), i.e. the flux of biochemical energy, which is shared
      between the reductive and oxidative cycles of carbon. The only reliable method to
      quantify the linear electron flux responsible for the production of reductive
      energy is to directly measure the O2 evolution by (18)O2 labelling and mass
      spectrometry. The hypothesis that the respective rates of reductive and oxidative
      cycles of carbon are only determined by the kinetic parameters of Rubisco, the
      respective concentrations of CO2 and O2 at the Rubisco site and the available
      electron transport rate, ultimately leads to propose new expressions of
      biochemical model equations. The modelling of (18)O2 and (16)O2 unidirectional
      fluxes in plants shows that a simple model can fit the photosynthetic and
      photorespiration exchanges for a wide range of environmental conditions. Its
      originality is to express the carboxylation and the oxygenation as a function of
      external gas concentrations, by the definition of a plant specificity factor Sp
      that mimics the internal reactions of Rubisco in plants. The difference between
      the specificity factors of plant (Sp) and of Rubisco (Sr) is directly related to
      the conductance values to CO2 transfer between the atmosphere and the Rubisco
      site. This clearly illustrates that the values and the variation of conductance
      are much more important, in higher C3 plants, than the small variations of the
      Rubisco specificity factor. The simple model systematically expresses the
      reciprocal variations of carboxylation and oxygenation exchanges illustrated by a
      "mirror effect". It explains the protective sink effect of photorespiration, e.g.
      during water stress. The importance of the CO2 compensation point, in classical
      models, is reduced at the benefit of the crossing points Cx and Ox, concentration
      values where carboxylation and oxygenation are equal or where the gross O2 uptake
      is half of the gross O2 evolution. This concept is useful to illustrate the
      feedback effects of photorespiration in the atmosphere regulation. The constancy
      of Sp and of Cx for a great variation of P under several irradiance levels shows
      that the regulation of the conductance maintains constant the internal CO2 and
      the ratio of photorespiration to photosynthesis (PR/P). The maintenance of the
      ratio PR/P, in conditions of which PR could be reduced and the carboxylation
      increased, reinforces the hypothesis of a positive role of photorespiration and
      its involvement in the plant-atmosphere co-evolution. 

PMID- 23153765
TI  - [Care pathways and physical and rehabilitation medicine, an update].

PMID- 23153766
TI  - Endoscopic thoracic sympathectomy for primary hyperhidrosis: a 16-year follow up
      in a single UK centre.
AB  - INTRODUCTION: Since the introduction of Endoscopic Thoracic Sympathectomy ( ETS )
      by Kux in 1951, the procedure has been performed for treatment of primary
      hyperhidrosis (PH) of the upper limb. Despite its initial success and minimally
      invasive nature, the long-term results are yet to be established. The aim of this
      study is to evaluate the outcome of patients after ETS with particular emphasis
      on patient satisfaction and its effectiveness over a 16-year period. METHODS: A
      patient survey of fifty-one (n = 51) patients who had ETS for PH of palms from
      1995 to 2011 was conducted. The data on age, sex, site of the PH, family history,
      trigger, hospital stay, relief from symptoms, complications, refractory sweating
      and overall satisfaction with the procedure was analysed with SAS software
      version 9.1.3. CONCLUSION: The mean follow-up was 77 months (range, 6-189 months)
      with equal gender distribution (n = 24 males Vs n = 27 females) and mean age of
      19 (range, 13-64 years). The hereditary prevalence was 55%. Forty-six patients
      (90.2%) reported an immediate (<=24 h) and four patients (7.8%) reported a delay
      (>24 h) in relief of symptoms. To the best of our knowledge this is longest
      duration of follow-up reported in the literature.

PMID- 23153767
TI  - [Ocular phototoxicity and altitude among mountain guides].
AB  - PURPOSE: This study aimed to evaluate ocular phototoxicity in mountaineer guides
      who experience overexposure to ultraviolet related to the altitude at which they
      work, as well as light reflection on snow. MATERIALS AND METHODS: Ninety-six
      guides and 90 controls living in plains, over 50 years old, underwent complete
      examinations. They responded to a questionnaire assessing altitude exposure and
      protective eyewear. We compared the two groups and performed a logistic
      regression within the guide group so as to identify risk and protective factors.
      RESULTS: Guides develop more ocular surface diseases. They exhibit more anterior
      cortical cataract (P<0.01) and cataract surgery (P=0.01). Only 61.5% of guides
      had a normal ocular fundus versus 81.1% in control group (P<0.01). They exhibit
      more drusen (27.2% vs. 15.6%, P<0.01). Among the guide group, exposure at an
      altitude above 3000 m is risk factor for anterior cortical cataract (OR=1.16,
      P<0.01). Wearing ski masks (OR=0.50, P=0.04) or photochromic lenses (OR=0.53,
      P=0.03) reduces this risk. Exposure to snow increases the risk of maculopathy
      (OR=1.9, P<0.01). Wearing a hat reduces this risk (OR=0.40, P=0.02) and the risk
      of cataract formation (OR=0.46, P=0.04). CONCLUSIONS: Guides develop more ocular
      surface diseases, anterior cortical lens opacities and drusen. These results
      underscore the potential deleterious role of ultraviolet radiation and the
      importance of light reflection on snow. The best ocular protection includes
      sunglasses and a hat with a visor or brim.

PMID- 23153768
TI  - Impact of glutathione S-transferase T1 gene polymorphisms on acute cellular
      rejection in living donor liver transplantation.
AB  - It has previously been demonstrated that glutathione S-transferase T1 (GSTT1)
      genetic mismatch between recipient and donor is a risk factor for developing
      immune-mediated hepatitis following liver transplantation and for antibody
      mediated rejection in renal transplantation. Little is known whether the GSTT1
      gene polymorphism affects the incidence of acute cellular rejection (ACR)
      following living donor liver transplantation (LDLT). Patients underwent LDLT at
      Nagoya University or Kyoto University, Japan, between 2004 and 2009. Genotyping
      of GSTT1 genes (null or present genotype) was conducted in recipients and donors.
      A total of 155 LDLT cases were examined. Forty-seven recipients (30.3%) developed
      early ACR. There was no association of recipient GSTT1 genotype with ACR
      incidence. However, ACR incidence was significantly higher in recipients
      transplanted from GSTT1 present genotype donors than in those transplanted from
      GSTT1 null genotype donors [odds ratio (OR)=2.64, 95% confidence interval
      (CI)=1.12-5.83, p=0.016]. Moreover, GSTT1 recipient/donor genotype mismatch
      (present/null or null/present) was significantly associated with ACR development
      (OR=2.28, 95% CI=1.12-4.61, p=0.022). The genotyping of GSTT1 in recipients and
      donors might be useful to stratify the liver transplant recipients according to
      risk of ACR.

PMID- 23153769
TI  - Impact of NF-kappaB gene polymorphism on allograft outcome in Hispanic renal
      transplant recipients.
AB  - BACKGROUND: The dimeric NF-kappaB transcription factors play critical roles in
      diverse cellular processes including adaptive and innate immunity, cell
      differentiation, proliferation and apoptosis. It regulates the expression of
      numerous genes that play a key role in the inflammatory response during kidney
      allograft rejection. This study aims to determine the association of NF-kappaB
      gene polymorphisms with allograft outcomes in the Hispanic renal transplant
      recipients. METHODS: A total of 607 Hispanic renal transplant recipients at St.
      Vincent Medical Center between 2001 and 2010 were included in this study. The NF
      kappaB genotypes were studied along with clinical data. In the case of NF-kappaB
      genotypes, the following single nucleotide polymorphisms (SNPs) were included: NF
      kappaB1 (rs3774959, rs3774932, rs3774937, rs230526, rs230519), NF-kappaB2
      (rs1056890, rs7897947, rs12769316) and NF-kappaB inducing kinase (NIK)
      (rs9908330, rs7222094). The association of each genotype with renal allograft
      survival and acute rejection was evaluated. RESULTS: NF-kappaB1 (rs3774937) CC
      genotype showed protective association with allograft rejection (OR=0.66, 95%
      CI=0.44-0.99, p=0.04). There was a significant increase in allograft survival
      time associated with the NF-kappaB1 (rs3774959) A allele (OR=0.76, 95% CI=0.60
      0.98, p=0.03) while GG genotype was associated with a higher risk of graft
      failure (OR=1.51, 95% CI=1.02-2.21, p=0.03). There were no associations between
      polymorphic markers in NF-kappaB2 and NIK genes with allograft survival or acute
      rejection. Among non-genetic factors, we found that the use of tacrolimus, a
      deceased donor, delayed graft function and acute rejection were associated with
      allograft failure. CONCLUSION: The result of present study suggests that NF
      kappaB1 gene polymorphisms may determine the incidence of acute rejection or
      graft survival among Hispanic allograft recipients.

PMID- 23153770
TI  - Presacral schwannoma.
AB  - Presacral schwannoma is a rare tumor, diagnosed essentially by pelvi-rectal
      digital examination. Diagnostic investigations should include initial CT-scan
      followed by pelvic MRI. The role of angiography and preoperative biopsy remain
      debated. Management is surgical: several surgical routes are possible to remove
      the tumor; resection essentially consists of enucleation.

PMID- 23153771
TI  - Single umbilical incision laparoscopic cholecystectomy: results of the
      prospective trial of the Coelio Club.
AB  - AIM: To assess the cosmetic outcome after single umbilical incision laparoscopic
      cholecystectomies (SILC) performed by the surgeons of the Coelio Club. PATIENTS
      AND METHODS: Multicenter prospective study concerning 105 consecutive patients
      operated between December 2009 and February 2011 by SILC for non-complicated
      gallstones. Perioperative and postoperative parameters were analyzed with a
      systematic follow-up at 1 and 6months postoperative. RESULTS: Conversion to
      conventional laparoscopic cholecystectomy (CLC) was required for six patients
      (5.7%). Conversion rate is higher in case of acute cholecystitis (25%, P<0.001).
      Cosmetic outcome is found excellent by the patient (in 86% of the cases at
      6months) and by the surgeon (in 90% of the cases at 6months) using an EVA scale.
      An incisional hernia was found in two cases (1.9%) and a superficial wound
      infection in four cases (3.8%). CONCLUSIONS: The cosmetic outcome after SILC is
      found excellent. SILC has its place in the surgical management of the non
      complicated gallstone. We did not notice higher level of peroperative
      complications (biliary tract injury) during SILC than during CLC. Postoperative
      higher level of abdominal wall complications than after a CLC makes the surgeon
      caution to a careful abdominal wall closure.

PMID- 23153772
TI  - Opportunities for policy interventions to reduce youth hookah smoking in the
      United States.
AB  - Preventing youth smoking initiation is a priority for tobacco control programs,
      because most adult tobacco smokers become addicted during adolescence.
      Interventions that restrict the affordability, accessibility, and marketing of
      cigarettes have been effective in reducing youth cigarette smoking. However,
      increasing numbers of youth are smoking tobacco using hookahs. Predictors of
      smoking tobacco with hookahs are the same as those for smoking cigarettes.
      Established interventions that curb youth cigarette smoking should therefore be
      effective in reducing hookah use. Potential policy interventions include
      equalizing tobacco tax rates for all tobacco types, requiring warning labels on
      hookah tobacco and accurate labeling of product contents, extending the cigarette
      flavoring ban to hookah tobacco, enacting smoke-free air laws and removing
      exemptions for hookah lounges, and expanding shipping restrictions on tobacco
      products.

PMID- 23153773
TI  - Prevalence of high body mass index among children and adolescents at a US
      military treatment facility, 2008-2009.
AB  - We assessed the prevalence of high body mass index (BMI) in a large cohort of
      military children. We compared BMI data from electronic medical records of
      military children aged 2 to 18 years with BMI data from the National Health and
      Nutrition Examination Survey (NHANES). The 23,778 military children studied were
      significantly less likely than the NHANES children to be overweight (27.1% vs
      31.8%) or obese (11.9% vs 16.9%). Even though military parents are required to
      maintain fitness and weight standards, the absolute difference between military
      and civilian children was small.

PMID- 23153774
TI  - Regulation of apical growth and hyphal branching in Streptomyces.
AB  - The filamentous bacteria Streptomyces grow by tip extension and through the
      initiation of new branches, and this apical growth is directed by a polarisome
      like complex involving the essential polarity protein DivIVA. New branch sites
      must be marked de novo and, until recently, there was no understanding of how
      these new sites are selected. Equally, hyphal branching patterns are affected by
      environmental conditions, but there was no insight into how polar growth and
      hyphal branching might be regulated in response to external or internal cues.
      This review focuses on recent discoveries that reveal the principal mechanism of
      branch site selection in Streptomyces, and the first mechanism to be identified
      that regulates polarisome behaviour to modulate polar growth and hyphal
      branching.

PMID- 23153775
TI  - Enhanced degradation of 2-nitrotoluene by immobilized cells of Micrococcus sp.
      strain SMN-1.
AB  - Nitrotoluenes are the toxic pollutants of the environment because of their large
      scale use in the production of explosives. Biodegradation of such chemicals by
      microorganisms may provide an effective method for their detoxification. We have
      studied the degradation of 2-nitrotoluene by cells of Micrococcus sp. strain SMN
      1 immobilized in various matrices such as polyurethane foam (PUF), sodium
      alginate (SA), sodium alginate-polyvinyl alcohol (SA-PVA), agar and
      polyacrylamide. The rate of degradation of 15 and 30 mM 2-nitrotoluene by freely
      suspended cells and immobilized cells in batches and fed-batch with shaken
      cultures were compared. The PUF-immobilized cells achieved higher degradation of
      15 and 30 mM 2-nitrotoluene than freely suspended cells and the cells immobilized
      in SA-PVA, polyacrylamide, SA and agar. The PUF-immobilized cells could be reused
      more than 24 cycles without loosing their degradation capacity and showed more
      tolerance to pH and temperature changes than freely suspended cells. These
      results revealed the enhanced rate of degradation of 2-nitrotoluene by PUF
      immobilized cells of Micrococcus sp. strain SMN-1.

PMID- 23153776
TI  - Application of ozone for the removal of bisphenol A from water and wastewater--a
      review.
AB  - The extensive use of Bisphenol A (BPA) in the plastics industry has led to
      increasing reports of its presence in the aquatic environment, with
      concentrations of ng L(-1) to MUg L(-1). Various advanced oxidation processes,
      including ozonation, have been shown to effectively degrade BPA. This paper
      reviews the current advancements in using ozone to remove BPA from water and
      wastewater. Most of the published work on the oxidation of BPA by ozone has
      focused on the efficiency of BPA removal in terms of the disappearance of BPA,
      and the effect of various operational parameters such as ozone feed rate, contact
      time and pH; some information is available on the estrogenic activity of the
      treated water. Due to increasing operational reliability and cost effectiveness,
      there is great potential for industrial scale application of ozone for the
      treatment of BPA. However, there is a significant lack of information on the
      formation of oxidation by-products and their toxicities, particularly in more
      complex matrices such as wastewater, and further investigation is needed for a
      better understanding of the environmental fate of BPA.

PMID- 23153777
TI  - Tributyltin exposure causes lipotoxicity responses in the ovaries of rockfish,
      Sebastiscus marmoratus.
AB  - Tributyltin (TBT) is a well-studied endocrine disruptor in mollusks and fishes.
      Recently, TBT is also recognized as a metabolic disruptor. Since abnormal lipids
      metabolism can induce negative effects on reproduction, the present study was
      designed to investigate the effects of TBT on ovarian lipid accumulation and
      testosterone esterification in rockfish (Sebastiscus marmoratus). After exposure
      for 48 d, there was a decrease of neutral lipid droplets in the ooplasm of
      ovaries. Exposure has also induced lipotoxicity responses in the ovaries, which
      shown as an increase of interstitial ectopic lipid accumulation and total lipids.
      The decrease of serum triiodothyronine and thyroxine concentrations might be
      responsible for the lipotoxicity responses. In addition, the percentage of
      testosterone in an esterified form was significantly decreased in the ovaries by
      TBT exposure, which might be a mechanism by which free testosterone levels
      increased. The accumulation of ectopic lipids and increase of free testosterone
      levels in the ovaries might impact ovarian functions and oocyte development in
      fish. These results strongly indicate that TBT exposure can influence
      reproductive functions of rockfish through lipotoxic mechanism.

PMID- 23153778
TI  - [Invasion of the spinal column by a posterior mediastinal cavernous haemangioma:
      a combined surgical approach].

PMID- 23153779
TI  - [Afferent loop stimulation prior to ileostomy closure].
AB  - There is a 17% complications rate after ileostomy closure, with paralytic ileus
      being the most common. With the aim of reducing this complication, stimulation
      via the afferent loop was performed daily for the 2 weeks prior to the stoma.

PMID- 23153780
TI  - [Evaluation of the gastrointestinal quality of life index as a system to
      prioritize patients on the waiting list for laparoscopic cholecystectomy].
AB  - INTRODUCTION: We prospectively evaluated health-related quality of life (HRQoL)
      through the gastrointestinal quality of life index (GIQLI) as a system to
      prioritize patients on the waiting list for laparoscopic cholecystectomy (LC) and
      its correlation with a linear prioritization system developed in the General and
      Gastrointestinal Surgery Institute of Clinica Quiron in Valencia. MATERIAL AND
      METHODS: There were 100 consecutive patients who underwent elective outpatient
      LC. The main outcome measures consisted of: 1) assessment of the impact of the
      disease, measured through the GIQLI; 2) evaluation of an objective system based
      on technical scientific criteria; 3) evaluation of the utility of LC in improving
      HRQoL through the GIQLI by analyzing expected and obtained utility through the
      change ratio, and 4) analysis of the correlation between the objective linear
      system, HRQoL and utility. RESULTS: The GIQLI was useful in evaluating the impact
      of the disease. LC significantly improved HRQoL in both oligosymptomatic and
      symptomatic patients. The objective or clinical factors did not allow perceptions
      of the process to be evaluated or the impact on HRQoL to be measured or inferred.
      A prioritization system based on GIQLI scores allows patients to be selected
      according to the expected utility (worsening of HRQoL) and obtained utility
      (improvement in HRQoL) of CL. CONCLUSIONS: Prioritization systems should include
      utility to guarantee equity. The GIQLI shows the impact of the disease on the
      patient while the clinical/objective factors are unrelated to the expectation of
      prioritization. Prioritization systems should include both elements to maintain
      the balance between impact and appropriate indication.

PMID- 23153781
TI  - Clinical implications of novel variants of the fibularis (peroneus) quartus
      muscle inserting onto the cuboid bone: peroneocuboideus and
      peroneocalcaneocuboideus.
AB  - Two variants of the fibularis (peroneus) quartus muscle were identified and
      photographed in the legs of a 70-year-old white male cadaver. A rare
      peroneocuboideus (fibulocuboideus) muscle (as described by Chudzinski) and a
      novel peroneocalcaneocuboideus (fibulocalcaneocuboideus) muscle was found in the
      right and left leg, respectively. The latter muscle has not been previously
      reported and was termed "peroneocalcaneocuboideus" on the basis of its origin and
      insertions. Also, the distal attachment of both muscles inserted onto the distal
      lip of the peroneal sulcus of the cuboid bone, which differs from the historical
      data. The insertion of the peroneocuboideus muscle was previously described as
      being at the tuberosity of the cuboid bone or, simply, the lateral surface of the
      cuboid. Therefore, the present case study provides the first gross anatomic
      photographs of these variant leg muscles along their entire length, identifies a
      novel fibularis quartus variant, and describes a new insertion site for the
      peroneocuboideus muscle. Throughout our report, the historical data are reviewed
      to list the prevalence and describe the clinical implications of the fibularis
      quartus muscle and its variants. The presence of variant fibularis quartus
      muscles has been known to cause lateral ankle pain and stenosis, ankle
      instability, fibular tenosynovitis, subluxation of the fibular (peroneal)
      tendons, and longitudinal splitting of the fibularis brevis tendon in radiologic
      and case studies. Therefore, surgeons, radiologists, and clinicians should be
      aware of these variant muscles when considering various diagnoses, interpreting
      radiographs, and pursuing surgical intervention to relieve lateral ankle
      pathologic features.

PMID- 23153782
TI  - Perioperative complications of a modular stem fixed-bearing total ankle
      replacement with intramedullary guidance.
AB  - Despite improved total ankle replacement outcomes, investigators have
      demonstrated that the incidence of complications after total ankle replacement is
      a function of the surgeon's experience with the technique. We hypothesized that
      the use of an intramedullary guide during a modular stem fixed-bearing total
      ankle replacement would decrease the incidence of perioperative complications and
      produce a similar incidence of complications across time. Because all patients
      were mobilized early, we also evaluated the influence of early mobilization on
      wound development. The medical records were reviewed to identify complications,
      and the radiographs were evaluated to determine the component alignment of the
      initial 58 consecutive ankles. Major wound complications were defined as
      complications requiring soft tissue coverage by a plastic surgeon. Minor wound
      complications were defined as those that could be treated without a return to the
      operating room. The procedures were separated into 2 groups: the initial 29
      procedures (group A) and latter 29 procedures (group B). Eight ankles (14%) had
      wound complications. The incidence of complications was similar across time [r(s)
      (56) = -0.06, p = .64]. The incidence of complications and component misalignment
      was similar for groups A and B (p >= .19). All wounds were diagnosed within 15
      days of surgery. None of the ankles developed wounds after physical therapy
      began. These results have demonstrated that the modular stem fixed-bearing total
      ankle replacement with intramedullary guidance can produce a similar incidence of
      complications over time, regardless of surgeon experience. Additionally, early
      mobilization did not appear to influence the incidence of wound complications and
      should be advocated, when appropriate.

PMID- 23153783
TI  - Talar neck fractures: a systematic review of the literature.
AB  - Considerable controversy surrounds the management of talar neck fractures
      regarding the rate of post-traumatic arthrosis, secondary procedures, avascular
      necrosis, and the effect of the interval to surgery on these variables. A data
      search using PubMed was performed with the keywords "talus" and "fracture." The
      search found 1280 studies. Ultimately, 21 reports involving 943 talar neck
      fractures were analyzed. Data concerning open fractures, the interval to surgery
      and its relationship to the incidence of avascular necrosis, and the rates of
      malunion and nonunion, post-traumatic arthrosis, secondary salvage procedures,
      and functional outcomes were collected and analyzed. The variables examined were
      not uniformly reported in all studies. The overall rate of avascular necrosis was
      33%, with no demonstrated relationship between the interval to surgery and the
      rate of avascular necrosis. Malunion occurred approximately 17% of the time, with
      nonunion occurring approximately 5% of the time. Post-traumatic arthrosis
      occurred in 68% of patients, although secondary salvage procedures were only
      performed in 19% of patients. Functional outcomes were difficult to assess, given
      the variability of reported outcomes and unvalidated measures. The optimal
      management of talar neck fractures has yet to be determined. Although the present
      review has improved understanding of these difficult fractures, additional
      studies that use validated outcomes measures are warranted to determine the
      effect of delayed surgery on final outcomes and optimal treatment methods.

PMID- 23153784
TI  - Subtalar joint septic arthritis in a patient with hypogammaglobulinemia.
AB  - The clinical presentation of a monoarticular, red, hot, and swollen joint has
      many possible diagnoses, including septic arthritis, which is 1 of the most
      devastating. The morbidity associated with this pathologic process involves
      permanent joint damage and the potential for progression to systemic illness and,
      even, mortality. The common risk factors for joint sepsis include a history of
      rheumatoid arthritis, previous joint surgery, joint prosthesis, intravenous drug
      abuse, alcoholism, diabetes, previous intra-articular steroid use, and cutaneous
      ulceration. The diagnosis is primarily determined from the culture results after
      arthrocentesis and correlation with direct visualization, imaging, and various
      serologies, including synovial analysis. In the present report, a case of an
      insidious presentation of subtalar joint septic arthritis and its association
      with a unique patient presentation concomitant with primary immunodeficiency and
      culture-proven Myocplasma hominis infection is discussed. Septic arthritis has a
      predilection for the lower extremities and typically is isolated to the hip or
      knee, with less common involvement of the ankle or metatarsophalangeal joints.
      Owing to the uncommon nature of primary immunodeficiency disorders and the
      paucity of studies discussing their association with septic arthridites, we aimed
      to raise awareness of subtalar joint septic arthritis and to provide a brief
      overview of the pathogenesis as it presented in a 33-year-old male with X-linked
      hypogammaglobulinemia/agammaglobulinema.

PMID- 23153785
TI  - Skeletal and dental stability of segmental distraction of the anterior mandibular
      alveolar process. A 5.5-year follow-up.
AB  - 17 patients (14 female; 3 male) were analysed retrospectively for skeletal and
      dental relapse before distraction osteogenesis (DO) of the mandibular anterior
      alveolar process at T1 (17.0 days), after DO at T2 (mean 6.5 days), at T3 (mean
      24.4 days), at T4 (mean 2.0 years), and at T5 (mean 5.5 years). Lateral
      cephalograms were traced by hand, digitized, superimposed, and evaluated.
      Skeletal correction (T5-T1) was mainly achieved through the distraction of the
      anterior alveolar segment in a rotational manner where the incisors were more
      proclined. The horizontal backward relapse (T5-T3) measured -0.3mm or 8.3% at
      point B (non-significant) and -1.8mm or 29.0% at incision inferior (p<0.01). Age,
      gender, amount and type (rotational vs. translational) of advancement were not
      correlated with the amount of relapse. High angle patients (NL/ML'; p<0.01)
      showed significant smaller relapse rates at point B. Overcorrection of the
      overjet achieved by the distraction could be a reason for dental relapse.
      Considering the amount of long-term skeletal relapse the DO could be an
      alternative to bilateral sagittal split osteotomy for mandibular advancement in
      selected cases.

PMID- 23153786
TI  - Rehabilitation of edentulous posterior atrophic mandible: inferior alveolar nerve
      lateralization by piezotome and immediate implant placement.
AB  - The height and consistency of the bone tissue located above the inferior alveolar
      nerve (IAN) represents an important challenge when a patient's atrophied
      posterior mandible is rehabilitated with an osseointegrated implant. Usually, the
      surgical reconstruction of atrophic ridges is performed using several different
      techniques. The purpose of this study is to demonstrate the effectiveness and
      safety of the inferior alveolar nerve lateralization (IANL) technique performed
      with ultrasonic cutting technology (piezotome). To demonstrate this, 38
      osseointegrated implants (11-15 mm in length) were performed during 19 procedures
      on 15 different patients. After 8 weeks, 14 of those 15 patients (18 of 19 sites:
      94.73%) showed normal IAN function. The implant success rate was 97.36%.

PMID- 23153787
TI  - Bone anchoring of sutures for adequate repositioning of the soft tissue flaps in
      one stage dental implants.
AB  - The choice of suture material and technique is important to optimize wound
      healing. If surgical wound edges are not properly approximated healing may be
      delayed because blood may accumulate under the flap and separate it from the
      underlying bone. The authors present an alternative suturing technique. They use
      a 'C suture' to fix and minimize mobilization of the soft tissues around non
      submerged implants.

PMID- 23153788
TI  - Carotid cavernous fistula after surgically assisted rapid maxillary expansion
      with a bone anchored appliance.
AB  - Surgically assisted rapid maxillary expansion (SARME) is an effective and stable
      method for treating severe maxillary transverse discrepancies in skeletally
      mature individuals, but it has potential complications. The authors report the
      case of a 34-year-old woman who developed carotid cavernous fistula after
      undergoing SARME with a bone anchored appliance and discuss the possible
      etiological basis of this condition.

PMID- 23153790
TI  - Label-free quantitative proteomics trends for protein-protein interactions.
AB  - Understanding protein interactions within the complexity of a living cell is
      challenging, but techniques coupling affinity purification and mass spectrometry
      have enabled important progress to be made in the past 15 years. As
      identification of protein-protein interactions is becoming easier, the
      quantification of the interaction dynamics is the next frontier. Several
      quantitative mass spectrometric approaches have been developed to address this
      issue that vary in their strengths and weaknesses. While isotopic labeling
      approaches continue to contribute to the identification of regulated
      interactions, techniques that do not require labeling are becoming increasingly
      used in the field. Here, we describe the major types of label-free quantification
      used in interaction proteomics, and discuss the relative merits of data dependent
      and data independent acquisition approaches in label-free quantification. This
      article is part of a Special Issue entitled: From protein structures to clinical
      applications.

PMID- 23153789
TI  - Usefulness of stereotactic biopsy and neuroimaging in management of HIV-1 Clade C
      associated focal brain lesions with special focus on cerebral toxoplasmosis.
AB  - BACKGROUND: Focal brain lesions (FBL) in HIV/AIDS frequently pose a diagnostic
      dilemma as the etiology varies from infective (tuberculoma, toxoplasmosis and
      tuberculous abscesses) to neoplastic lesions like lymphoma. For determining
      etiology, advanced neuroimaging techniques, serological and molecular biological
      tests have been evolved with varying sensitivities/specificities. Stereotactic
      biopsy (STB) of the lesions is reserved for lesions unresponsive to appropriate
      therapy. OBJECTIVE AND METHODS: In this study, the diagnostic yield of
      neuroimaging [cranial CT (n=25), MRI (n=24), and Th201/99Tc SPECT scan (n=18)] is
      compared with histopathological diagnosis obtained by STB (n=21) or autopsy (n=4)
      in 25 HIV-1 subtype C seropositive individuals with FBL identified by
      neuroimaging with special reference to cerebral toxoplasmosis in an eighteen
      month study period (2006-2007). RESULTS AND CONCLUSION: Cerebral toxoplasmosis
      was the most frequent cause of FBL (21/25, 84%), followed by one case each of
      tuberculoma, progressive multifocal leukoencephalopathy (PML), primary central
      nervous system lymphoma (PCNSL) and measles inclusion body encephalitis (MIBE),
      the last two diagnosed at autopsy. Of the 21 cases of cerebral toxoplasmosis,
      definitive diagnosis with histopathological confirmation was available in 14/21
      (66.6%), with indirect evidence suggesting probable toxoplasmosis in seven, all
      of whom responded to antitoxoplasma therapy. CT and MRI had comparable
      specificities (75%), while MRI had marginally higher sensitivity (85% versus
      80.9%) in detecting multiple lesions. The positive predictive value of both CT
      and MRI was identical (94.4%), suggesting that CT maybe a cost effective
      screening tool in resource restricted settings, for evaluating FBL. Sensitivity
      of 99Tc SPECT scan for diagnosing inflammatory lesions was 75% but failed to
      differentiate PCNSL from toxoplasmosis. This study is the first of its kind from
      India analyzing FBL with specific focus on cerebral toxoplasmosis in the setting
      of HIV-1 subtype C.

PMID- 23153791
TI  - Change in protein content during seed germination of a high altitude plant
      Podophyllum hexandrum Royle.
AB  - Podophyllum hexandrum Royle (=Sinopodophyllum hexandrum) is a high-altitude
      medicinal plant exploited for its etoposides which are potential anticancer
      compounds. An effective, conventional propagation method is by seed. However,
      seed germination is erratic, and seedling survival is low. A marginal increase in
      Podophyllum seed germination was attained with organic solvents. In the present
      study an attempt was made to decipher the physiological and biochemical barriers
      in terms of change in proteins during seed germination of Podophyllum.
      Comparative 2-DE analysis between un-germinated (dormant) and germinating seeds
      revealed nearly 113 differentially expressed proteins, whereas Peptide Mass
      Fingerprint (PMF) analysis of 97 protein spots revealed appearance of 27
      proteins, up-accumulation of 11 proteins, down-accumulation of 19 proteins and
      disappearance of 40 proteins with germination. Identified 59 proteins in the
      homology search were involved in metabolism (carbohydrate and amino acid
      metabolism; 20 proteins), ABA/GA signaling (17 proteins) and stress (15 proteins)
      related proteins. Seven proteins were with unknown function. Two-DE, and MS/MS
      analysis in conjunction with semi-quantitative RT-PCR data of cell wall
      hydrolyzing genes, revealed that in Podophyllum the radicle protrusion occurs
      might be because of the up-accumulation of cell wall hydrolases i.e. beta-1, 3
      glucanase and XET which weakens the thick walled micropylar endosperm.

PMID- 23153793
TI  - Improved proteomic profiling of the cell surface of culture-expanded human bone
      marrow multipotent stromal cells.
AB  - A comprehensive analysis of the membrane proteome is essential to explain the
      biology of multipotent stromal cells and identify reliable protein biomarkers for
      the isolation as well as tracking of cells during differentiation and maturation.
      However, proteomic analysis of membrane proteins is challenging and they are
      noticeably under-represented in numerous proteomic studies. Here we introduce new
      approach, which includes high pressure-assisted membrane protein extraction,
      protein fractionation by gel-eluted liquid fraction entrapment electrophoresis
      (GELFREE), and combined use of liquid chromatography MALDI and ESI tandem mass
      spectrometry. This report presents the first comprehensive proteomic analysis of
      membrane proteome of undifferentiated and culture-expanded human bone marrow
      multipotent stromal cells (hBM-MSC) obtained from different human donors. Gene
      ontology mapping using the Ingenuity Pathway Analysis and DAVID programs revealed
      the largest membrane proteomic dataset for hBM-MSC reported to date.
      Collectively, the new workflow enabled us to identify at least two-fold more
      membrane proteins compared to published results on hBM-MSC. A total of 84 CDs
      were identified including 14 CDs identified for the first time. This dataset can
      serve as a basis for further exploration of self-renewal, differentiation and
      characterization of hBM-MSC.

PMID- 23153792
TI  - Recent advances in cardiovascular proteomics.
AB  - Cardiovascular diseases (CVDs) are the major source of global morbidity and death
      and more people die annually from CVDs than from any other cause. These diseases
      can occur quickly, as seen in acute myocardial infarction (AMI), or progress
      slowly over years as with chronic heart failure. Advances in mass spectrometry
      detection and analysis, together with improved isolation and enrichment
      techniques allowing for the separation of organelles and membrane proteins, now
      allow for the indepth analysis of the cardiac proteome. Here we outline current
      insights that have been provided through cardiovascular proteomics, and discuss
      studies that have developed innovative technologies which permit the examination
      of the protein complement in specific organelles including exosomes and secreted
      proteins. We highlight these foundational studies and illustrate how they are
      providing the technologies and tools which are now being applied to further study
      cardiovascular disease; provide new diagnostic markers and potentially new
      methods of cardiac patient management with identification of novel drug targets.
      This article is part of a Special Issue entitled: From protein structures to
      clinical applications.

PMID- 23153794
TI  - Whole-exome sequencing reveals recurrent somatic mutation networks in cancer.
AB  - The second-generation sequencing technologies have been extensively used to
      reveal the mechanism of tumorigenesis and find critical genes in cancer
      progression that can be potential targets of clinic treatment. Exome is a part of
      genome formed by exons which are the protein-coding portions of genes. The whole
      exome sequencing information can reflect the mutations of the protein-coding
      region in the genome and depict the causal relationship between the mutations and
      phenotypes. Now, many network-based methods have been developed to identify
      cancer driver modules or pathways, which not only provide new insights into
      molecular mechanism of disease progression at network level but also can avoid
      low coverage or lowly recurrent on disease samples in contrast to individual
      driver genes. In this review, we focus on the recent advances on network-based
      methods for identifying cancer driver modules or pathways, including methods of
      whole-exome sequencing, somatic mutation detection, driver mutation
      identification, and mutation network reconstruction. 

PMID- 23153795
TI  - Cytokines: how important are they in mediating sickness?
AB  - Sickness refers to a set of coordinated physiological and behavioral changes in
      response to systemic inflammation. It is characterized by fever, malaise, social
      withdrawal, fatigue, and anorexia. While these responses collectively represent a
      protective mechanism against infection and injury, increasing lines of evidence
      indicate that over-exaggerated or persistent sickness can damage the brain, and
      could possibly raise the risk to developing delirium. Therefore, a clear
      understanding in sickness will be beneficial. It has long been believed that
      sickness results from increased systemic cytokines occurring during systemic
      inflammation. However, in recent years more and more conflicting data have
      suggested that development of sickness following peripheral immune challenge
      could be independent of cytokines. Hence, it is confusing as to whether cytokines
      really do act as primary mediators of sickness, or if they are secondary to
      alternative inducing factor(s). In this review, we will (1) introduce the
      relationships between systemic inflammation, cytokines, sickness, and delirium,
      and (2) attempt to interpret the recent controversies.

PMID- 23153796
TI  - Multiple subregions in superior temporal cortex are differentially sensitive to
      vocal expressions: a quantitative meta-analysis.
AB  - Vocal expressions of emotions consistently activate regions in the superior
      temporal cortex (STC), including regions in the primary and secondary auditory
      cortex (AC). Studies usually report broadly extended functional activations in
      response to vocal expressions, with considerable variation in peak locations
      across several auditory subregions. This might suggest different and distributed
      functional roles across these subregions instead of a uniform role for the
      decoding of vocal emotions. We reviewed recent studies and conducted an
      activation likelihood estimation meta-analysis summarizing recent fMRI and PET
      studies dealing with the processing of vocal expressions in the STC and AC. We
      included two stimulus-specific factors (paraverbal/nonverbal expression, stimulus
      valence) and one task-specific factor (attentional focus) in the analysis. These
      factors considerably influenced whether functional activity was located in the AC
      or STC (influence of valence and attentional focus), the laterality of
      activations (influence of paraverbal/nonverbal expressions), and the anterior
      posterior location of STC activity (influence of valence). These data suggest
      distributed functional roles and a differentiated network of auditory subregions
      in response to vocal expressions.

PMID- 23153797
TI  - Synthesis, characterization and biological studies of diosgenyl analogues.
AB  - A series of optical amino acid diosgenyl esters and diosgenyl salicylate
      conjugates were designed and synthesized to develop new anticancer and anti
      inflammatory agents. The analogue 9c that contains an 6-aminohexanoic acid
      residue at C-3 of diosgenin exhibits higher potency against all three tumor cell
      lines with IC(50) values ranging from 4.7 MUM in C26 cells to 14.6 MUM in Hep G2
      cells. In addition, seven of newly synthesized compounds significantly inhibit
      xylene-induced ear edema and exhibit comparable or better anti-inflammatory
      activities than those of diosgenin and aspirin. Furthermore, preliminary
      structure-activity relationship studies demonstrate that diosgenyl salicylate
      conjugates have stronger anti-inflammatory activities than amino acid diosgenyl
      esters.

PMID- 23153799
TI  - Spatial analysis of corresponding fingerprint features from match and close non
      match populations.
AB  - The development of statistical models for forensic fingerprint identification
      purposes has been the subject of increasing research attention in recent years.
      This can be partly seen as a response to a number of commentators who claim that
      the scientific basis for fingerprint identification has not been adequately
      demonstrated. In addition, key forensic identification bodies such as ENFSI [1]
      and IAI [2] have recently endorsed and acknowledged the potential benefits of
      using statistical models as an important tool in support of the fingerprint
      identification process within the ACE-V framework. In this paper, we introduce a
      new Likelihood Ratio (LR) model based on Support Vector Machines (SVMs) trained
      with features discovered via morphometric and spatial analyses of corresponding
      minutiae configurations for both match and close non-match populations often
      found in AFIS candidate lists. Computed LR values are derived from a
      probabilistic framework based on SVMs that discover the intrinsic spatial
      differences of match and close non-match populations. Lastly, experimentation
      performed on a set of over 120,000 publicly available fingerprint images (mostly
      sourced from the National Institute of Standards and Technology (NIST) datasets)
      and a distortion set of approximately 40,000 images, is presented, illustrating
      that the proposed LR model is reliably guiding towards the right proposition in
      the identification assessment of match and close non-match populations. Results
      further indicate that the proposed model is a promising tool for fingerprint
      practitioners to use for analysing the spatial consistency of corresponding
      minutiae configurations. 

PMID- 23153798
TI  - Identification of novel series of pyrazole and indole-urea based DFG-out PYK2
      inhibitors.
AB  - Previous drug discovery efforts identified classical PYK2 kinase inhibitors such
      as 2 and 3 that possess selectivity for PYK2 over its intra-family isoform FAK.
      Efforts to identify more kinome-selective chemical matter that stabilize a DFG
      out conformation of the enzyme are described herein. Two sub-series of PYK2
      inhibitors, an indole carboxamide-urea and a pyrazole-urea have been identified
      and found to have different binding interactions with the hinge region of PYK2.
      These leads proved to be more selective than the original classical inhibitors.

PMID- 23153800
TI  - Virtual anthropology: a comparison between the performance of conventional X-ray
      and MDCT in investigating the trabecular structure of long bones.
AB  - Recently, modern cross-sectional imaging techniques such as multi-detector
      computed tomography (MDCT) have pioneered post mortem investigations, especially
      in forensic medicine. Such approaches can also be used to investigate bones non
      invasively for anthropological purposes. Long bones are often examined in
      forensic cases because they are frequently discovered and transferred to medico
      legal departments for investigation. To estimate their age, the trabecular
      structure must be examined. This study aimed to compare the performance of MDCT
      with conventional X-rays to investigate the trabecular structure of long bones.
      Fifty-two dry bones (24 humeri and 28 femora) from anthropological collections
      were first examined by conventional X-ray, and then by MDCT. Trabecular structure
      was evaluated by seven observers (two experienced and five inexperienced in
      anthropology) who analyzed images obtained by radiological methods. Analyses
      contained the measurement of one quantitative parameter (caput diameter of
      humerus and femur) and staging the trabecular structure of each bone. Preciseness
      of each technique was indicated by describing areas of trabecular destruction and
      particularities of the bones, such as pathological changes. Concerning
      quantitative parameters, the measurements demonstrate comparable results for the
      MDCT and conventional X-ray techniques. In contrast, the overall inter-observer
      reliability of the staging was low with MDCT and conventional X-ray. Reliability
      increased significantly when only the results of the staging performed by the two
      experienced observers were compared, particularly regarding the MDCT analysis.
      Our results also indicate that MDCT appears to be better suited to a detailed
      examination of the trabecular structure. In our opinion, MDCT is an adequate tool
      with which to examine the trabecular structure of long bones. However, adequate
      methods should be developed or existing methods should be adapted to MDCT.

PMID- 23153801
TI  - The role of micro-computed tomography in forensic investigations.
AB  - The use of micro-CT within forensic practice remains an emerging technology,
      principally due to its current limited availability to forensic practitioners.
      This review provides those with little or no previous experience of the potential
      roles of micro-CT in forensic practice with an illustrated overview of the
      technology, and the areas of practice in which micro-CT can potentially be
      applied to enhance forensic investigations.

PMID- 23153802
TI  - Statistical evaluation of the influence of writing postures on on-line
      signatures. Study of the impact of time.
AB  - The aim of this study is to investigate the influence of unusual writing
      positions on a person's signature, in comparison to a standard writing position.
      Ten writers were asked to sign their signature six times, in each of four
      different writing positions, including the standard one. In order to take into
      consideration the effect of the day-to-day variation, this same process was
      repeated over 12 sessions, giving a total of 288 signatures per subject. The
      signatures were collected simultaneously in an off-line and on-line acquisition
      mode, using an interactive tablet and a ballpoint pen. Unidimensional variables
      (height to width ratio; time with or without in air displacement) and time
      dependent variables (pressure; X and Y coordinates; altitude and azimuth angles)
      were extracted from each signature. For the unidimensional variables, the
      position effect was assessed through ANOVA and Dunnett contrast tests. Concerning
      the time-dependent variables, the signatures were compared by using dynamic time
      warping, and the position effect was evaluated through classification by linear
      discriminant analysis. Both of these variables provided similar results: no
      general tendency regarding the position factor could be highlighted. The
      influence of the position factor varies according to the subject as well as the
      variable studied. The impact of the session factor was shown to cover the impact
      that could be ascribed to the writing position factor. Indeed, the day-to-day
      variation has a greater effect than the position factor on the studied signature
      variables. The results of this study suggest guidelines for best practice in the
      area of signature comparisons and demonstrate the importance of a signature
      collection procedure covering an adequate number of sampling sessions, with a
      sufficient number of samples per session. 

PMID- 23153803
TI  - Karyotype polymorphism and chromosomal rearrangement in populations of the
      phytopathogenic fungus, Ascochyta rabiei.
AB  - The fungus Ascochyta rabiei is the causal agent of Ascochyta blight of chickpea
      and the most serious threat to chickpea production. Little is currently known
      about the genome size or organization of A. rabiei. Given recent genome
      sequencing efforts, characterization of the genome at a population scale will
      provide a framework for genome interpretation and direction of future
      resequencing efforts. Electrophoretic karyotype profiles of 112 isolates from 21
      countries revealed 12-16 chromosomes between 0.9 Mb and 4.6 Mb with an estimated
      genome size of 23 Mb-34 Mb. Three general karyotype profiles A, B, and C were
      defined by the arrangement of the largest chromosomes. Approximately one-third of
      isolates (group A) possessed a chromosome larger than 4.0 Mb that was absent from
      group B and C isolates. The ribosomal RNA gene (rDNA) cluster was assigned to the
      largest chromosome in all except four isolates (group C) whose rDNA cluster was
      located on the second largest chromosome (3.2 Mb). Analysis of progeny from an in
      vitro sexual cross between two group B isolates revealed one of 16 progeny with
      an rDNA-encoding chromosome larger than 4.0 Mb similar to group A isolates, even
      though a chromosome of this size was not present in either parent. No expansion
      of the rDNA cluster was detected in the progeny, indicating the increase in
      chromosome size was not due to an expansion in number of rDNA repeats. The
      karyotype of A. rabiei is relatively conserved when compared with published
      examples of asexual ascomycetes, but labile with the potential for large scale
      chromosomal rearrangements during meiosis. The results of this study will allow
      for the targeted sequencing of specific isolates to determine the molecular
      mechanisms of karyotype variation within this species.

PMID- 23153804
TI  - Molecular phylogenetic analyses based on the nuclear rRNA genes and the intron
      exon structures of the nuSSU rRNA gene in Dictyocatenulata alba (anamorphic
      Ascomycota).
AB  - Molecular phylogenies inferred from the nuclear small subunit rRNA gene (nuSSU),
      nuclear large subunit rRNA gene D1/D2 region (nuLSU), and ITS-5.8S rRNA gene
      (ITS) indicated that five cultures of the lichenized hyphomycete Dictyocatenulata
      alba isolated from Japan form a monophyletic clade with high bootstrap support,
      and a close relationship to the Ostropomycetidae (Lecanoromycetes,
      Pezizomycotina, Ascomycota). Insertion sequences were found in the nuSSU of all
      isolates [e.g., nine insertions in the strain JCM 5358 (Japan Collection of
      Microorganisms)], some of which were group I introns. Five new insertion
      positions were found among the D. alba isolates. Using BLAST, none of the
      insertion sequences of D. alba were closely related to those of fungi or other
      organisms deposited in public DNA databases. Insertion positions were similar in
      some isolates, and two positions were common to all isolates. Although all
      phylogenetic analyses based on nuSSU, nuLSU, and ITS revealed the monophyly of D.
      alba, the isolates were divided into two (in the nuSSU tree) or three (in the
      nuLSU and ITS trees) groups. Based on the phylogenetic analyses and the intron
      exon structures, the five isolates identified as D. alba belong to three cryptic
      species and therefore D. alba should be considered a species complex. The very
      slow-growing, tough agar colonies of the isolates, the occurrence of the species
      on both slightly lichenized and nonlichenized surfaces of trees, or pebbles
      (rarely on soil), suggest that the members of the D. alba complex may be
      lichenized. The photobiont was not clearly identified in this study.

PMID- 23153805
TI  - Molecular phylogeny and phenotypic variability of clinical and environmental
      strains of Aspergillus flavus.
AB  - Aspergillus flavus is the second most common cause of aspergillosis infection in
      immunocompromised patients and is responsible for the production of aflatoxins.
      Little is known about the population structure of A. flavus, although recent
      molecular and phenotypic data seem to demonstrate that different genetic lineages
      exist within this species. The aim of this study was to carry out a
      morphological, physiological, and molecular analysis of a set of clinical and
      environmental isolates to determine whether this variability is due to species
      divergence or intraspecific diversity, and to assess whether the clinical
      isolates form a separate group. The amdS and omtA genes were more
      phylogenetically informative than the other tested genes and their combined
      analysis inferred three main clades, with no clear distinction between clinical
      and environmental isolates. No important morphological and physiological
      differences were found between the members of the different clades, with the
      exception of the assimilation of d-glucosamine, which differentiates the members
      of the clade II from the others.

PMID- 23153806
TI  - Genome-wide identification and profiling of microRNA-like RNAs from Metarhizium
      anisopliae during development.
AB  - Metarhizium anisopliae is one of the most common species of entopathogenic fungi.
      It has economic and social benefits in many countries where used in agriculture
      as an important biological control agent of insect pests. M. anisopliae can exist
      as multiple cell types, which suggests that this fungus has a complex way of gene
      regulation. MicroRNAs (miRNAs) are endogenous small noncoding RNAs. They play a
      crucial role in the regulation of gene expression and cell function in plants,
      animals, and in fungi where they were termed miRNA-like RNAs (milRNAs). In this
      study, we aimed to identify potential milRNAs in M. anisopliae that may regulate
      the processes of mycelium growth and conidiogenesis (CO). Two small RNA (sRNA)
      libraries were constructed and submitted to Solexa sequencing. Fifteen milRNAs
      were identified using deep-sequencing and computational analysis; most of these
      milRNAs originated from single genes. Database searches revealed that these novel
      milRNAs had no homologues in other organisms and were, therefore, M. anisopliae
      specific. Many of the milRNAs had differential expression profiles for either
      mycelium growth or CO. The expression of the selected milRNAs was validated by
      quantitative reverse transcription polymerase chain reaction. Seventy-eight
      potential target mRNAs for 14 of the milRNAs were identified successfully by
      computational analysis. These milRNAs may play an important role in the
      regulation of mycelial growth and conidiation in M. anisopliae. To our knowledge,
      this study is the first report of milRNA profiles of organisms in the order
      Hypocreales. This information could be used to study the regulation of genes and
      their networks in M. anisopliae.

PMID- 23153807
TI  - Quantifying Hg within ectomycorrhizal fruiting bodies, from emergence to
      senescence.
AB  - Ectomycorrhizal fruiting bodies (basidiomata) collected from forested areas in
      southwestern New Brunswick were analyzed for total mercury, sulphur, nitrogen,
      and carbon concentrations (THg, TS, TN, and TC, respectively). This analysis was
      done for caps and stalks and by development stage (emergent, mature, senescent)
      across 27 species associated with five classes, eight families, and 13 genera.
      Across the species, THg correlated positively with TN and TS, thereby implying N
      as well as S mitigated transfer of Hg from the mycelia into the basidiomata, with
      THg ranging from 3 to 10 457 ppb. TS, TN, and TC varied from 0.07 to 1, 1 to 11,
      and 43 to 53 %, respectively. Cap and stalk THg, TS, TN, and TC were also
      correlated to one another, with mean stalk/cap ratios of 0.59, 0.76, 0.71, and
      0.98, respectively. Soil availability indexed by THg, TS, TN, and TC within the
      forest floor contributed to basidiomatal THg as well. THg, THg/TS, and THg/N
      varied strongly by species. These variations involved: (i) no growth dilution and
      no volatilization (Group I), (ii) growth dilution only (Group II), (iii) growth
      dilution followed by loss during senescence (Group III), and (iv) growth dilution
      combined with loss from emergence onward (Group IV). Depending on species, TN and
      TS remained the same or declined from 100 % at emergence to about 80 and 70 % at
      senescence. Lack of THg decline for the Group I species would be due to HgS
      encapsulation. Reanalyzing the freeze-dried samples revealed that THg continued
      to drop during the first year of air-dry storage for the Group II, II, and IV
      species, but TS, TN, and TC remained stable. The results were quantified by way
      of best-fitted regression models.

PMID- 23153808
TI  - Discovery of a fourth evolutionary lineage of Phytophthora ramorum: EU2.
AB  - Phytophthora ramorum is a recently introduced, aggressive Phytophthora species
      that has caused extensive mortality of oak and tanoak trees in the western USA
      and Japanese larch trees in the UK. P. ramorum is also present on Rhododendron,
      Camellia, and Viburnum in the nursery industry, which is thought to have been the
      pathway for its spread into new geographic regions including forests and natural
      ecosystems. Three lineages of P. ramorum have been described, informally
      designated EU1, NA1, and NA2, and each lineage is believed to originate from an
      as yet unknown exotic centre of origin. Preliminary SSR and sequence analysis of
      isolates from a UK P. ramorum survey revealed seven isolates with profiles that
      did not match the previously known lineages. Detailed SSR and multilocus sequence
      analysis of these isolates are presented, allowing us to assign these isolates to
      a new P. ramorum lineage, designated EU2. Although the known geographical origin
      of these isolates is currently limited to Northern Ireland and western Scotland,
      the EU2 lineage isolates have been obtained from four different host plants,
      including Japanese larch. All isolates are of A1 compatibility type, which
      implies that this finding does not increase the risk of outcrossing with the EU1
      lineage isolates already present in the UK. The oldest EU2 strain was isolated in
      2007 but no SSR-based intraEU2 lineage genotypic diversity was detected. The
      combination of these elements points to a recent introduction, despite emergency
      phytosanitary measures to control introduction and spread. A PCR-RFLP method for
      the rapid identification of EU2 lineage isolates is presented.

PMID- 23153809
TI  - Multiple-scale environmental modulation of lichen reproduction.
AB  - It is necessary to understand how environmental changes affect plant fitness to
      predict survival of a species, but this knowledge is scarce for lichens and
      complicated by their formation of sexual and asexual reproductive structures. Are
      the presence and number of reproductive structures in Lobaria pulmonaria, a
      threatened lichen, dependent on thallus size, and is their formation sequential?
      Does any size-dependence and sequential formation vary along a climate gradient?
      Generalized linear mixed models were used to explore the effect of environmental
      predictors on the size and presence/abundance of each reproductive structure and
      to determine the probability of a given-sized thallus to develop any reproductive
      structure. The largest individuals are more likely to develop reproductive
      structures, and the lichen uses a mixed strategy of early asexual reproduction
      and late sexual. Macro and microclimatic variables also influenced reproductive
      capacity. Relationships among climate conditions and lichen size and reproductive
      capacity can compromise the future viability of the species in the most southern
      populations of Europe.

PMID- 23153810
TI  - Lignopurines: a new family of hybrids between cyclolignans and purines. Synthesis
      and biological evaluation.
AB  - A new family of hybrids between cyclolignans related to podophyllic aldehyde, a
      non-lactonic cyclolignan, and purines were prepared and evaluated against several
      human tumour cell lines. Both fragments, cyclolignan and purine, were linked
      through aliphatic and aromatic chains. The influence on the cytotoxicity of the
      purine substitution and the nature of the linker is analyzed. The new family was
      slightly less cytotoxic than the parent podophyllic aldehyde, although the
      selectivity is maintained or even improved and among the linkers used, the
      presence of an aromatic ring gave the most potent and selective derivatives
      within the new series tested. Cell cycle and confocal studies demonstrate that
      these derivatives interfere with the tubulin polymerization and arrest cells at
      the G(2)/M phase, in the same way than the parent compounds podophyllotoxin and
      podophyllic aldehyde do.

PMID- 23153811
TI  - Hesperetin: an inhibitor of the transforming growth factor-beta (TGF-beta)
      signaling pathway.
AB  - We have identified a previously unknown function of the natural compound,
      hesperetin. Here, we demonstrate that this small molecular agent is able to
      inhibit the transforming growth factor-beta (TGF-beta) signaling pathway. Single
      molecule force measurements and single-molecule fluorescence imaging show that
      hesperetin interferes with ligand-receptor interactions. Furthermore, by Western
      blot analysis, it was confirmed that hesperetin also inhibits the phosphorylation
      of Smad3, a down-stream target of the TGF-beta pathway. In addition we
      demonstrated that this compound hinders TGF-beta1-induced cancer cell migration
      and invasion. These results suggest a potential future application for hesperetin
      as a TGF-beta inhibitor in cancer therapy.

PMID- 23153812
TI  - Recent advances in the development of selective human MAO-B inhibitors:
      (hetero)arylidene-(4-substituted-thiazol-2-yl)hydrazines.
AB  - A large series of (4-substituted-thiazol-2-yl)hydrazine derivatives was
      synthesized in good yield and assayed for their in vitro human monoamine oxidase
      (hMAO) inhibitory activity and selectivity. Most of them showed inhibitory
      activity in the nanomolar range and hMAO-B selective inhibition higher than
      reference drugs, demonstrating our interest in this privileged scaffold. The
      structure-activity relationship of the different rings on the N1-hydrazine
      position indicated that a pyridine ring was preferred with the presence of
      electron-withdrawing substituents on the aryl group at C4 of the thiazole
      nucleus. The substituent on the alpha-carbon to the N1-hydrazine moiety (methyl
      or hydrogen) had a great influence on the activity and hMAO-B selectivity.
      Moreover, the reversibility of the enzyme inhibition for the best active compound
      was reported.

PMID- 23153813
TI  - Synthesis and antiproliferative activity of helonioside A, 3',4',6'-tri-O
      feruloylsucrose, lapathoside C and their analogs.
AB  - The first total synthesis of natural phenylpropanoid sucrose esters (PSEs)
      helonioside A 1, 3',4',6'-tri-O-feruloylsucrose 2 and lapathoside C 3 along with
      17 unnatural PSE analogs has been successfully accomplished in a short and simple
      synthetic route. A selected set of 17 synthesized PSEs were evaluated for the
      antiproliferative activity against human cervical epithelioid carcinoma (HeLa)
      cell lines using MTS assay method. Eleven (11) compounds showed significant
      antiproliferative activity with their IC(50)values ranging from 0.16 to 6.01 MUM.
      The structure-activity-relationship studies revealed that the antiproliferative
      activity is influenced by the lipophilicity and number of feruloyl substituents
      on these compounds. The preliminary screening indicated that these compounds are
      potentially very valuable source for new lead chemotherapeutics.

PMID- 23153814
TI  - Application of a post-docking procedure based on MM-PBSA and MM-GBSA on single
      and multiple protein conformations.
AB  - In the last decades, molecular docking has emerged as an increasingly useful tool
      in the modern drug discovery process, but it still needs to overcome many hurdles
      and limitations such as how to account for protein flexibility and poor scoring
      function performance. For this reason, it has been recognized that in many cases
      docking results need to be post-processed to achieve a significant agreement with
      experimental activities. In this study, we have evaluated the performance of MM
      PBSA and MM-GBSA scoring functions, implemented in our post-docking procedure
      BEAR, in rescoring docking solutions. For the first time, the performance of this
      post-docking procedure has been evaluated on six different biological targets
      (namely estrogen receptor, thymidine kinase, factor Xa, adenosine deaminase,
      aldose reductase, and enoyl ACP reductase) by using i) both a single and a
      multiple protein conformation approach, and ii) two different software, namely
      AutoDock and LibDock. The assessment has been based on two of the most important
      criteria for the evaluation of docking methods, i.e., the ability of known
      ligands to enrich the top positions of a ranked database with respect to
      molecular decoys, and the consistency of the docking poses with crystallographic
      binding modes. We found that, in many cases, MM-PBSA and MM-GBSA are able to
      yield higher enrichment factors compared to those obtained with the docking
      scoring functions alone. However, for only a minority of the cases, the
      enrichment factors obtained by using multiple protein conformations were higher
      than those obtained by using only one protein conformation.

PMID- 23153815
TI  - Analysis of the discriminative inhibition of mammalian digestive lipases by 3
      phenyl substituted 1,3,4-oxadiazol-2(3H)-ones.
AB  - We report here the reactivity and selectivity of three 5-Methoxy-N-3-Phenyl
      substituted-1,3,4-Oxadiazol-2(3H)-ones (MPOX, as well as meta and para
      PhenoxyPhenyl derivatives, i.e.MmPPOX and MpPPOX) with respect to the inhibition
      of mammalian digestive lipases: dog gastric lipase (DGL), human (HPL) and porcine
      (PPL) pancreatic lipases, human (HPLRP2) and guinea pig (GPLRP2) pancreatic
      lipase-related proteins 2, human pancreatic carboxyl ester hydrolase (hCEH), and
      porcine pancreatic extracts (PPE). All three oxadiazolones displayed similar
      inhibitory activities on DGL, PLRP2s and hCEH than the FDA-approved anti-obesity
      drug Orlistat towards the same enzymes. These compounds appeared however to be
      discriminative of HPL (poorly inhibited) and PPL (fully inhibited). The
      inhibitory activities obtained experimentally in vitro were further rationalized
      using in silico molecular docking. In the case of DGL, we demonstrated that the
      phenoxy group plays a key role in specific molecular interactions within the
      lipase's active site. The absence of this group in the case of MPOX, as well as
      its connectivity to the neighbouring aromatic ring in the case of MmPPOX and
      MpPPOX, strongly impacts the inhibitory efficiency of these oxadiazolones and
      leads to a significant gain in selectivity towards the lipases tested. The
      powerful inhibition of PPL, DGL, PLRP2s, hCEH and to a lesser extend HPL,
      suggests that oxadiazolone derivatives could also provide useful leads for the
      development of novel and more discriminative inhibitors of digestive lipases.
      These inhibitors could be used for a better understanding of individual lipase
      function as well as for drug development aiming at the regulation of the whole
      gastrointestinal lipolysis process.

PMID- 23153816
TI  - Synthesis of novel 12-aryl-8,9,10,12-tetrahydrobenzo[a]xanthene-11-thiones and
      evaluation of their biocidal effects.
AB  - Novel 12-aryl-8,9,10,12-tetrahydrobenzo[a]xanthene-11-thiones have been
      synthesized in high yields by treatment of the corresponding oxo analogs with
      Lawesson's reagent. The structure has been confirmed by X-ray analysis. The
      compounds were tested for in vitro antifungal activity against Rhizoctonia
      bataticola, Sclerotium rolfsii, Fusarium oxysporum and Alternaria porii. The
      compounds exhibited moderate to good activity against all pathogens. Insecticidal
      activity of these compounds against Spodoptera litura was observed to be
      comparable to commercial pyrethroid insecticide, cypermethrin. The urease
      inhibitory activity has also been studied.

PMID- 23153817
TI  - Vascular access strategy for delivering long-term antimicrobials to patients with
      infective endocarditis: device type, risk of infection and mortality.
AB  - BACKGROUND: This paper reports the use of different vascular access devices and
      the incidence of intravascular catheter-related infection (CRI) in patients
      receiving intravenous antibiotics for infective endocarditis (IE). AIM: To
      examine whether rates of infection vary with type of vascular access device, and
      assess the impact of CRI on mortality in IE. METHODS: A prospective observational
      service evaluation of all inpatients who received intravenous antibiotics for IE
      was performed. In total, 114 inpatients were evaluated. All cases of CRI
      [including exit-site infection, intravascular catheter-related bloodstream
      infection (CRBSI) and mortality] were recorded. Tunnelled and non-tunnelled
      central venous catheters (CVCs), and peripherally inserted cannulae were used for
      antibiotic delivery. FINDINGS: There were 15 episodes of CRI, 11 of which were
      CRBSI (all associated with CVC use). The remainder comprised uncomplicated exit
      site infections. Use of tunnelled CVCs [hazard ratio (HR) 16.95, 95% confidence
      interval (CI) 2.13-134.93; P = 0.007] and non-tunnelled CVCs (HR 24.54, 95% CI
      2.83-212.55; P = 0.004) was associated with a significantly increased risk of
      CRI. Risk of mortality increased significantly with Staphylococcus aureus as the
      cause of IE (P < 0.001) and CRBSI (P = 0.034). CONCLUSION: Risk of CRI in
      patients with IE is linked to the type of vascular access device used. Rates of
      CRBSI were greatest with CVCs, while peripheral venous cannulae were not
      associated with CRBSI or serious sequelae. Many patients (40%) tolerated complete
      treatment courses delivered via peripheral cannulae. These findings confirm the
      importance of device selection in reducing the risk of CRI; a potentially
      modifiable variable that impacts on outcome and mortality in IE.

PMID- 23153818
TI  - Haploinsufficiency of the autism candidate gene Neurobeachin induces autism-like
      behaviors and affects cellular and molecular processes of synaptic plasticity in
      mice.
AB  - Neurobeachin (NBEA), a brain-enriched multidomain scaffolding protein involved in
      neurotransmitter release and synaptic functioning, has been identified as a
      candidate gene for autism spectrum disorder (ASD) in four unrelated patients
      haploinsufficient for NBEA. The aim of this study was to map the behavioral
      phenotype of Nbea(+/-) mice in order to understand its contribution to the
      pathogenesis of ASD. ASD-like behavioral variables of Nbea(+/-) mice were related
      to basal neuronal activity in different brain regions by in situ hybridizations
      and extracellular field recordings of synaptic plasticity in hippocampal cornu
      ammonis 1 (CA1) region. Levels of BDNF and phosphorylated cAMP response element
      binding protein (CREB) were measured in an attempt to investigate putatively
      underlying changes in these neuromolecules. Nbea(+/-) mice exhibit several ASD
      like features, including changes in self-grooming behavior, social behaviors,
      conditioned fear responses, and spatial learning and memory, which coincided with
      enhanced long-term potentiation (LTP) in their CA1 region. The observed
      alterations in learning and memory and hippocampal LTP are concomitant with
      decreased expression of the immediate early gene zif268 in dorsomedial striatum
      and hippocampal CA1 region, increased CREB phosphorylation, and increased
      hippocampal BDNF expression. These findings indicate that Nbea haploinsufficiency
      leads to various molecular and cellular changes that affect neuroplasticity and
      behavioral functions in mice, and could thus underlie the ASD symptomatology in
      NBEA deficient humans.

PMID- 23153819
TI  - A novel human enterovirus C (EV-C118) identified in two children hospitalised
      because of acute otitis media and community-acquired pneumonia in Israel.
AB  - We report the discovery of a novel enterovirus C (EV-C118) identified in two
      Israeli children hospitalised for acute otitis media and community-acquired
      pneumonia. The highest pair-wise sequence identity scores with the EV-C109 and EV
      C117 reference strains were, respectively, 63.5% and 63.6% nucleotide identity,
      and 82.5% and 79.9% amino acid identity.

PMID- 23153820
TI  - The value of CMV IgG avidity and immunoblot for timing the onset of primary CMV
      infection in pregnancy.
AB  - BACKGROUND: Primary CMV infections in pregnancy are usually asymptomatic and only
      detected by serology. Estimating the onset of infection is a major diagnostic
      goal, since primary infections around conception and in early gestation hold a
      higher risk for congenital disease than those in later pregnancy. OBJECTIVES: To
      assess the ability of serological supplementary CMV assays to date the onset of
      primary infection. STUDY DESIGN: From our routine diagnosis we identified 61
      pregnant women (n=188 serum samples) with precisely determined onset of CMV
      primary infection either by IgG seroconversion (n=24) or by significant IgG
      antibody rise (n=37). One hundred and forty-seven sera were investigated using
      the VIDAS((r)) CMV IgG avidity EIA (BioMerieux) and 83 sera using the recomBlot
      CMV IgG with avidity (Mikrogen). RESULTS: Both assays proofed to be reliable in
      terms of timing the onset of CMV primary infection. An avidity index (AI) in the
      VIDAS avidity EIA of <40% indicated primary infection within the last 20 weeks
      (positive predictive value 93.4%; 99/106), whereas an intermediate AI excluded
      primary infection within the last 12 weeks (negative predictive value 88.2%;
      15/17). The recomBlot showed high reliability (PPV 96.9%; 31/33) for timing the
      onset of infection within the last 14 weeks. Avidity testing by blot however
      could not be interpreted in 11 of 47 sera (23.4%). CONCLUSION: For timing the
      onset of infection (before or in early pregnancy) CMV avidity testing is most
      helpful if carried out within the first trimester up to the beginning of second
      trimester.

PMID- 23153822
TI  - Apportioning global and non-global components of mercury deposition through
      (210)Pb indexing.
AB  - Our previous work has documented a correlation between Hg concentrations and
      (210)Pb activity measured in wet deposition that might be used to help apportion
      sources of Hg in precipitation. Here we present the results of a 27-month
      precipitation collection effort using co-located samplers for Hg and (210)Pb
      designed to assess this hypothesis. Study sites were located on the east and west
      coasts of North America, in the continental interior, and on the Florida
      Peninsula. Relatively high variability in Hg/(210)Pb ratios was found at all
      sites regionally and seasonally (e.g., overall: 0.99-9.13ngdpm(-1)). The ratio of
      average volume-weighted Hg concentrations and (210)Pb activities showed
      consistent trends (higher in impacted area), with Glacier Bay in southeast
      Alaska, exhibiting the lowest value. Assuming that Glacier Bay represents a
      benchmark for a site with no regional contribution, we estimate less than 50% of
      the Hg input was "global" at the Seattle and Florida sites. Differences in
      Hg/(210)Pb in wet deposition could be due to either a regional/local source
      contribution of Hg, or a regional/local enhancement in the removal of Hg from the
      atmosphere (i.e., oxidants), however, this approach is not capable of discerning
      between these two possibilities. Thus, this method of source apportionment
      represents an estimate of the maximal amount of Hg contributed by regional
      sources and may be limited in regions of deep convective mixing.

PMID- 23153821
TI  - A norovirus outbreak in a nursing home: norovirus shedding time associated with
      age.
AB  - BACKGROUND: Norovirus (NoV) GII.4 has been identified as predominant in outbreaks
      in the long-term health-care facilities. OBJECTIVES: NoV excretion during an
      outbreak of gastroenteritis affecting 19/42 residents and 12/33 employees was
      investigated in a Taiwan nursing home. STUDY DESIGN: Real-time reverse
      transcription polymerase chain reaction (RT-PCR) was used to quantify viral RNA
      from stool samples up to the point of negative detection. RESULTS: Initial fecal
      viral loads in affected residents were higher than in affected employees
      (p=0.024). Viral reduced rate was measured as 0.66/day, with a viral half-life of
      1.7 days. A mixed model indicated that time (days post-illness onset), initial
      virus load and resident status (as opposed to employee status) were the most
      important determining factors of fecal NoV concentration. According to a
      univariable accelerated failure time (AFT) model, strong associations existed
      between virus excretion duration and both age (p=0.005) and resident status
      (p=0.004). No associations were noted between viral excretion duration and either
      initial viral load or diarrhea duration. According to a multivariable AFT model,
      age was the only factor affecting virus excretion duration. CONCLUSION: In
      conclusion, outbreaks in nursing homes may have resulted from environmental
      contamination, the existence of asymptomatic residents and prolonged virus
      shedding time in the elderly and care providers. This outbreak finished quickly
      because frequent cleaning of the surface was done and contact precautions were
      taken for prolonged viral shedding residents.

PMID- 23153823
TI  - In vitro diagnosis of the first case of amitraz resistance in Rhipicephalus
      microplus in Santo Tome (Corrientes), Argentina.
AB  - In Argentina, the cattle tick Rhipicephalus microplus has already developed
      resistance to organophosphates and synthetic pyrethroids. However, no cases of
      amitraz resistance have ever been recorded in this country despite its heavy use.
      A recent failure of amitraz to control ticks in a farm located in Santo Tome,
      province of Corrientes, resulted in the collection of samples for acaricide
      resistance diagnosis. The modified Drummond adult immersion test (AIT) and the
      larval tarsal test (LTT) were performed separately in Argentina and Switzerland
      to evaluate efficacy of amitraz and other acaricides. The AIT showed that
      oviposition in the Santo Tome field isolate was not inhibited when it was
      challenged to 250 and 500 ppm amitraz, and 50 ppm deltamethrin. However,
      oviposition was reduced by 90.6% when this field isolate was challenged to a
      combination of 400 ppm ethion and 100 ppm cypermethrin. To confirm the results
      obtained with the AIT, 2 additional tick samples were collected and shipped to
      Switzerland for resistance diagnosis of amitraz, cypermethrin and flumethrin,
      using the LTT. With this bioassay, the resistance ratios of the 2 field isolates
      were 32.5 and 57.0 for amitraz and between 5.9 and 27.2 for the synthetic
      pyrethroids. Both in vitro bioassays confirmed amitraz and synthetic pyrethroid
      resistance in the Santo Tome samples. These results account for the first
      evidence of amitraz resistance in R. microplus in Argentina.

PMID- 23153824
TI  - Canine visceral leishmaniasis: a comparative study of real-time PCR, conventional
      PCR, and direct agglutination on sera for the detection of Leishmania infantum
      infection.
AB  - Canine visceral leishmaniasis (CVL) is endemic in northwestern Iran. This study
      aimed to compare real-time PCR, conventional PCR, and the direct agglutination
      test (DAT) for the diagnosis Leishmania infantum infection in 167 serum samples
      of domestic dog. Bone marrow was used for parasitological examination (smears
      and/or culture) in symptomatic visceral leishmaniasis, and serum was used for
      detection of L. infantum kinetoplast DNA (kDNA) by both conventional PCR and real
      time PCR, while anti-L. infantum antibodies in sera were measured by DAT. The
      sera were collected from 37 symptomatic and 112 asymptomatic dogs during April to
      May 2011. Eighteen presumed negative samples were obtained from healthy dogs kept
      in non-endemic areas with no history of CVL and used as controls. All 18 samples
      were negative by DAT and Dipstick rK39. DAT confirmed previous exposure to L.
      infantum for all 149 serum samples collected from symptomatic and asymptomatic
      dogs in CVL endemic areas of Iran. Among the 37 symptomatic dogs, 20 (54%), 25
      (67.6%), 36 (97.3%), and 37 (100%) showed L. infantum infection by
      parasitological methods, conventional PCR, real-time PCR, and DAT (>= 1:80),
      respectively. Of 112 asymptomatic dogs, 79 (70.5%), 111 (99.1%), and 112 (100%)
      were shown to be positive by conventional PCR, and DAT (>= 1:80), respectively.
      For ethical reasons, no asymptomatic or healthy control dogs were examined by
      parasitological methods. Three (16.7%) control dogs were positive by real-time
      PCR, but were negative by DAT, dipstick rK39, and conventional PCR methods.
      Parasitemia levels were measured by real-time PCR targeting kDNA using SYBR((r))
      green assay. This quantitative technique detected infection in 89.9% (150/167) of
      the domestic dogs that harbored L. infantum kDNA, ranging from 0.01 49 to 310.1
      parasites/ml. The average was 16.60 parasites/ml. A good agreement (0.97) was
      found between real-time PCR and DAT at >= 1:80 titer, used as cut-off value by
      Kappa analysis. Thus, real-time PCR as a quantitative PCR assay on serum samples
      represents a valuable tool for initial diagnosis of CVL when whole blood is not
      available.

PMID- 23153825
TI  - Expression of autism spectrum and schizophrenia in patients with a 22q11.2
      deletion.
AB  - BACKGROUND: Copy number variants (CNVs) associated with neuropsychiatric
      disorders are increasingly being identified. While the initial reports were
      relatively specific, i.e. implicating vulnerability for a particular
      neuropsychiatric disorder, subsequent studies suggested that most of these CNVs
      can increase the risk for more than one neuropsychiatric disorder. Possibly, the
      different neuropsychiatric phenotypes associated with a single genetic variant
      are really distinct phenomena, indicating pleiotropy. Alternatively, seemingly
      different disorders could represent the same phenotype observed at different
      developmental stages or the same underlying pathogenesis with different
      phenotypic expressions. AIMS: To examine the relation between autism and
      schizophrenia in patients sharing the same CNV. METHOD: We interviewed parents of
      78 adult patients with the 22q11.2 deletion (22q11.2DS) to examine if autistic
      symptoms during childhood were associated with psychosis in adulthood. We used
      Chi-square, T-tests and logistic regression while entering cognitive level,
      gender and age as covariates. RESULTS: The subgroup of 22q11.2DS patients with
      probable ASD during childhood did not show an increased risk for psychosis in
      adulthood. The average SRS scores were highly similar between those with and
      those without schizophrenia. CONCLUSIONS: ASD and schizophrenia associated with
      22q11.2DS should be regarded as two unrelated, distinct phenotypic
      manifestations, consistent with true neuropsychiatric pleiotropy. 22q11.2DS can
      serve as a model to examine the mechanisms associated with neuropsychiatric
      pleiotropy associated with other CNVs.

PMID- 23153827
TI  - Mirror neurons (and beyond) in the macaque brain: an overview of 20 years of
      research.
AB  - Mirror neurons are a class of neurons in the ventral pre-motor cortex (area F5)
      and inferior parietal lobule (area PFG) that respond during the execution as well
      as the observation of goal-directed motor acts. These intriguing response
      properties stirred an intense debate in the scientific community with respect to
      the possible cognitive role of mirror neurons. The aim of the present review is
      to contribute to this debate by providing, in a single paper, an extended summary
      of 20 years of neurophysiological research on mirror neurons in the macaque. To
      this end, I provide a comprehensive description of the methodology and the main
      results of each paper about mirror neurons published since their first report in
      1992. Particular care was devoted in reporting the different response
      characteristics and the percentages of neurons exhibiting them in relation to the
      total number of studied neurons. Furthermore, I also discuss recent results
      indicating that mirror neurons might not be confined to areas F5 and PFG and that
      "mirroring" might not be limited to action observation. Finally, I offer a
      unifying framework for many of the results discussed here by speculating that a
      potential functional role of mirror neurons might be, during action observation,
      to generalize from the particular grasping movement being observed to the
      "concept" of grasping.

PMID- 23153828
TI  - Deletion of Crry, the murine ortholog of the sporadic Alzheimer's disease risk
      gene CR1, impacts tau phosphorylation and brain CFH.
AB  - Large-scale genome-wide SNP association studies have identified an association
      between variants of CR1, the gene encoding complement component receptor 1, and
      the sporadic form of Alzheimer's disease. The role of CR1 and the complement
      system in Alzheimer's disease remains far from clear. In rodents the closest
      ortholog of CR1 is the Crry gene (Cr1-related protein Y). To begin to explore its
      role in Alzheimer's disease we examined hippocampal lysates from Crry(-/-) mice
      and age matched controls by immunoblotting. We measured complement factor H, a
      component of the complement system and biomarker for Alzheimer's disease
      progression, and tau phosphorylation at the serine 235 site, hyperphosphorylated
      forms of tau being a defining neuropathological hallmark of the disease. We found
      that levels of CFH and of tau phosphorylation at serine 235 were strongly and
      significantly reduced in Crry(-/-) samples. These observations provide a starting
      point for further attempts to determine the role of CR1 in the neuropathological
      process driving Alzheimer's disease.

PMID- 23153829
TI  - Treadmill running and static stretching improve long-lasting hyperalgesia, joint
      limitation, and muscle atrophy induced by cast immobilization in rats.
AB  - The effects of exercise on chronic pain induced by immobilization are
      incompletely understood. The purpose of this study was to investigate whether
      30min of treadmill running (TR; active exercise) and 10min of static stretching
      (SS; passive exercise) of the immobilized hindlimb reduce widespread chronic
      pain, joint limitation, and hindlimb muscle atrophy induced by cast
      immobilization in rats. One hindlimb of Sprague Dawley (SD) rats was immobilized
      for 2 weeks with a cast, and remobilization was conducted for 7 weeks. MRI study
      showed that cast immobilization had induced inflammatory changes in the
      immobilized hindlimb, beginning as early as 2h after cast removal; these changes
      continued for 2-3 days. Mechanical hyperalgesia in the calf and hindpaw developed
      as early as 2h after cast removal and continued for 7 weeks. TR and SS were
      initiated 3 days after cast removal and were continued 3 times per week for 2
      weeks. Both forms of exercise significantly inhibited mechanical hyperalgesia in
      the calf and hindpaw in immobilized rats. Range-of-motion limitations in the knee
      and ankle joints and calf muscle atrophy after cast removal were also decreased
      by both TR and SS. This study is the first to demonstrate the beneficial effect
      of TR and SS on widespread chronic pain, joint limitation, and muscle atrophy in
      a cast-immobilized rat model.

PMID- 23153830
TI  - An in vitro comparison study: the effects of fetal bovine serum concentration on
      retinal progenitor cell multipotentiality.
AB  - Retinal progenitor cells (RPCs) are an excellent resource for retinal replacement
      therapy, because they show enormous potential to differentiate into retinal
      specific cell types. While the differentiating influence of serum has long been
      appreciated, the effects of serum concentration on RPC differentiation into
      specified retinal neural cells have not been investigated. Using cultured murine
      RPCs, this study compared the effects of different levels of fetal bovine serum
      (FBS) (1%, 5%, 10% and 20%) on RPC differentiation in vitro. RPC
      multipotentiality was assessed by using quantitative polymerase chain reaction
      (qPCR) to determine the relative expression levels of 10 genes involved in
      retinal development. In addition, analyses of cell morphology and retinal
      development-related protein expression were performed using microscopy and
      immunocytochemistry. The data revealed that 1% FBS-induced cultures
      preferentially generated rhodopsin- and PKC-alpha-positive cells. Calbindin and
      AP2alpha expression levels were greater in 5% FBS-induced cultures. Brn3a was
      expressed at similar levels in 1%, 5% and 10% FBS treatment conditions but
      diminished in 20% FBS conditions. Twenty percent FBS induced more glial
      fibrillary acid protein (GFAP)-immunoreactive cells corresponding to glia
      populations. These findings suggest that the concentration of FBS plays an
      important role in RPC differentiation in vitro. Treatment with low levels of FBS
      favors differentiation of rhodopsin-positive photoreceptors, interneurons and
      retinal ganglion cells (RGCs), while high FBS concentrations preferentially
      induce differentiation of glia cells. These results are expected to facilitate
      research in the treatment of neurodegenerative retinal diseases.

PMID- 23153831
TI  - [Which information is given to ALS patients carrying the pathogenic
      hexanucleotide repeat expansion of c9orf72?].

PMID- 23153832
TI  - [Foreword].

PMID- 23153826
TI  - Dysregulation of RNA polymerase I transcription during disease.
AB  - Transcription of the ribosomal RNA genes by the dedicated RNA polymerase I enzyme
      and subsequent processing of the ribosomal RNA are fundamental control steps in
      the synthesis of functional ribosomes. Dysregulation of Pol I transcription and
      ribosome biogenesis is linked to the etiology of a broad range of human diseases.
      Diseases caused by loss of function mutations in the molecular constituents of
      the ribosome, or factors intimately associated with RNA polymerase I
      transcription and processing are collectively termed ribosomopathies.
      Ribosomopathies are generally rare and treatment options are extremely limited
      tending to be more palliative than curative. Other more common diseases are
      associated with profound changes in cellular growth such as cardiac hypertrophy,
      atrophy or cancer. In contrast to ribosomopathies, altered RNA polymerase I
      transcriptional activity in these diseases largely results from dysregulated
      upstream oncogenic pathways or by direct modulation by oncogenes or tumor
      suppressors at the level of the RNA polymerase I transcription apparatus itself.
      Ribosomopathies associated with mutations in ribosomal proteins and ribosomal RNA
      processing or assembly factors have been covered by recent excellent reviews. In
      contrast, here we review our current knowledge of human diseases specifically
      associated with dysregulation of RNA polymerase I transcription and its
      associated regulatory apparatus, including some cases where this dysregulation is
      directly causative in disease. We will also provide insight into and discussion
      of possible therapeutic approaches to treat patients with dysregulated RNA
      polymerase I transcription. This article is part of a Special Issue entitled:
      Transcription by Odd Pols.

PMID- 23153833
TI  - [Acute hemolytic anemia in an HIV patient after inhalation of amyl nitrite].

PMID- 23153834
TI  - Traditional Chinese herbal medicine as a source of molecules with antiviral
      activity.
AB  - Traditional Chinese herbal medicine (TCHM) is widely used in the prevention and
      treatment of viral infectious diseases. However, the operative mechanisms of TCHM
      remain largely obscure, mainly because of its complicated nature and the
      fragmented nature of research. In recent years, systematic methodologies have
      been developed to discover the active compounds in TCHM and to elucidate its
      underlying mechanisms. In this review, we summarize recent progress in TCHM-based
      antiviral research in China and other Asian countries. In particular, this review
      focuses on progress in targeting key steps in the viral replication cycle and key
      cellular components of the host defense system. Recent developments in
      centralized and standardized TCHM screening and databases are also summarized.

PMID- 23153835
TI  - Gait variability and disability in multiple sclerosis.
AB  - Gait variability is clinically relevant in some populations, but there is limited
      documentation of gait variability in persons with multiple sclerosis (MS). This
      investigation examined average and variability of spatiotemporal gait parameters
      in persons with MS and healthy controls and subsequent associations with
      disability status. 88 individuals with MS (age 52.4+/-11.1) and 20 healthy
      controls (age 50.9+/-8.7) performed two self-paced walking trials on a 7.9-m
      electronic walkway to determine gait parameters. Disability was indexed by the
      Expanded Disability Status Scale (EDSS) and ranged between 2.5 and 6.5. Gait
      variability was indexed by standard deviation (SD) and coefficient of variation
      (CV=SD/mean) of step time, step length, and step width. Average gait parameters
      were significantly correlated with EDSS (rho=0.756-0.609) and were significantly
      different in individuals with MS compared to controls (p<=0.002). Also, step
      length (p<0.001) and step time (p<0.001) variability were both significantly
      greater in MS compared to controls. EDSS was positively correlated with step
      length variability and individuals with MS who used assistive devices to walk had
      significantly greater step length variability than those who walked independently
      (p's<.05). EDSS was correlated with step time and length variability even when
      age was taken into account. Additionally, Fisher's z test of partial correlations
      revealed that average gait parameters were more closely related to disability
      status than gait variability in individuals with MS. This suggests that focusing
      on average gait parameters may be more important than variability in therapeutic
      interventions in MS.

PMID- 23153836
TI  - The assessment of cervical sensory motor control: a systematic review focusing on
      measuring methods and their clinimetric characteristics.
AB  - BACKGROUND: Cervical sensorimotor control (CSMC) becomes increasingly important
      in the assessment and treatment of patients with neck pain. This review aims to
      compare commonly used CSMC measuring methods in terms of required tasks,
      measuring device and clinimetric properties. SEARCH METHODS: A systematic review
      of two databases, followed by methodological quality assessment (CBO guidelines).
      RESULTS: The methodological quality of 34 included articles was generally good
      (five to seven out of eight), the inter-rater agreement was excellent
      (kappaw=0.966, p<0.01). Following tasks were found: head repositioning accuracy
      to the neutral head position (HRA-to-NHP) and to a target position (HRA-to
      target), a virtual reality test, a continuous linear movement technique (CLMT)
      and an object following non-linear movement technique (NLMT) (The FlyTM). Test
      retest reliability was fair to excellent (ICC 0.35-0.87) for the HRA-to-NHP, very
      bad to excellent (ICC 0.01-0.90) for the HRA-to-target, fair to good (ICC 0.25
      0.77) for the virtual reality test and moderate to excellent (ICC: 0.60-0.86) for
      The FlyTM. The reliability of the CLMT was not documented. The HRA-to-NHP, The
      FlyTM and the CLMT can discriminate between patients with neck complaints and
      controls (discriminant validity). Currently, only The FlyTM can discriminate
      between different patient populations (post-traumatic and non-traumatic neck
      pain). The sensitivity, specificity and responsiveness of the methods have to be
      assessed in future research. CONCLUSIONS: The dynamic method The FlyTM appears to
      be more reliable than the HRA-to-NHP and is able to discriminate between
      different patient populations. The diagnostic potential is to be confirmed in
      future research.

PMID- 23153837
TI  - How politics trumped peer review at Texas cancer institute.

PMID- 23153838
TI  - Multiple enlarging nodules on the lower limb.

PMID- 23153839
TI  - Dry eye.

PMID- 23153840
TI  - Annual health checks for people with intellectual disabilities.

PMID- 23153841
TI  - Government disputes that half of NHS efficiency savings came from staff pay
      freeze.

PMID- 23153842
TI  - Carbamazepine-induced hypersensitivity syndrome in chronic schizophrenia.
AB  - Drug-induced hypersensitivity syndrome is a clinically important issue. We report
      a case of carbamazepine-induced hypersensitivity syndrome in a 35-year-old
      schizophrenia patient. This patient had no previous food or medication allergy
      history and presented a negative test result of HLA-B*1502 genotype. After 19
      days exposure of carbamazepine, high fever up to 39.4  degrees C, leucopenia
      (1670/mm3), proteinuria and bilateral lung field infiltration were developed.
      These clinically significant physical conditions resolved after discontinuing
      carbamazepine. The importance of genetic susceptibility other than HLA-B*1502
      should not be overlooked in drug-induced hypersensitivity syndrome.

PMID- 23153843
TI  - The effect of age on outcomes of coronary artery bypass surgery compared with
      balloon angioplasty or bare-metal stent implantation among patients with
      multivessel coronary disease. A collaborative analysis of individual patient data
      from 10 randomized trials.
AB  - OBJECTIVES: This study sought to assess whether patient age modifies the
      comparative effectiveness of coronary artery bypass graft (CABG) surgery and
      percutaneous coronary intervention (PCI). BACKGROUND: Increasingly, CABG and PCI
      are performed in older patients to treat multivessel disease, but their
      comparative effectiveness is uncertain. METHODS: Individual data from 7,812
      patients randomized in 1 of 10 clinical trials of CABG or PCI were pooled. Age
      was analyzed as a continuous variable in the primary analysis and was divided
      into tertiles for descriptive purposes (<=56.2 years, 56.3 to 65.1 years, >=65.2
      years). The outcomes assessed were death, myocardial infarction and repeat
      revascularization over complete follow-up, and angina at 1 year. RESULTS: Older
      patients were more likely to have hypertension, diabetes, and 3-vessel disease
      compared with younger patients (p < 0.001 for trend). Over a median follow-up of
      5.9 years, the effect of CABG versus PCI on mortality varied according to age
      (interaction p < 0.01), with adjusted CABG-to-PCI hazard ratios and 95%
      confidence intervals (CI) of 1.23 (95% CI: 0.95 to 1.59) in the youngest tertile;
      0.89 (95% CI: 0.73 to 1.10) in the middle tertile; and 0.79 (95% CI: 0.67 to
      0.94) in the oldest tertile. The CABG-to-PCI hazard ratio of less than 1 for
      patients 59 years of age and older. A similar interaction of age with treatment
      was present for the composite outcome of death or myocardial infarction. In
      contrast, patient age did not alter the comparative effectiveness of CABG and PCI
      on the outcomes of repeat revascularization or angina. CONCLUSIONS: Patient age
      modifies the comparative effectiveness of CABG and PCI on hard cardiac events,
      with CABG favored at older ages and PCI favored at younger ages.

PMID- 23153844
TI  - In silico cardiac risk assessment in patients with long QT syndrome: type 1:
      clinical predictability of cardiac models.
AB  - OBJECTIVES: The study was designed to assess the ability of computer-simulated
      electrocardiography parameters to predict clinical outcomes and to risk-stratify
      patients with long QT syndrome type 1 (LQT1). BACKGROUND: Although attempts have
      been made to correlate mutation-specific ion channel dysfunction with patient
      phenotype in long QT syndrome, these have been largely unsuccessful. Systems
      level computational models can be used to predict consequences of complex changes
      in channel function to the overall heart rhythm. METHODS: A total of 633 LQT1
      genotyped subjects with 34 mutations from multinational long QT syndrome
      registries were studied. Cellular electrophysiology function was determined for
      the mutations and introduced in a 1-dimensional transmural electrocardiography
      computer model. The mutation effect on transmural repolarization was determined
      for each mutation and related to the risk for cardiac events (syncope, aborted
      cardiac arrest, and sudden cardiac death) among patients. RESULTS: Multivariate
      analysis showed that mutation-specific transmural repolarization prolongation
      (TRP) was associated with an increased risk for cardiac events (35% per 10-ms
      increment [p < 0.0001]; >=upper quartile hazard ratio: 2.80 [p < 0.0001]) and
      life-threatening events (aborted cardiac arrest/sudden cardiac death: 27% per 10
      ms increment [p = 0.03]; >=upper quartile hazard ratio: 2.24 [p = 0.002])
      independently of patients' individual QT interval corrected for heart rate (QTc).
      Subgroup analysis showed that among patients with mild to moderate QTc duration
      (<500 ms), the risk associated with TRP was maintained (36% per 10 ms [p <
      0.0001]), whereas the patient's individual QTc was not associated with a
      significant risk increase after adjustment for TRP. CONCLUSIONS: These findings
      suggest that simulated repolarization can be used to predict clinical outcomes
      and to improve risk stratification in patients with LQT1, with a more pronounced
      effect among patients with a lower-range QTc, in whom a patient's individual QTc
      may provide less incremental prognostic information.

PMID- 23153845
TI  - In silico to in vivo: mutation-specific modeling of arrhythmia risk.

PMID- 23153846
TI  - Aged human cells rejuvenated by cytokine enhancement of biomaterials for surgical
      ventricular restoration.
AB  - OBJECTIVES: This study investigated whether cytokine enhancement of a
      biodegradable patch could restore cardiac function after surgical ventricular
      restoration (SVR) even when seeded with cells from old donors. BACKGROUND: SVR
      can partially restore heart size and improve function late after an extensive
      anterior myocardial infarction. However, 2 limitations include the stiff
      synthetic patch used and the limited healing of the infarct scar in aged
      patients. METHODS: We covalently immobilized 2 proangiogenic cytokines (vascular
      endothelial growth factor and basic fibroblast growth factor) onto porous
      collagen scaffolds. We seeded human mesenchymal stromal cells from young (50.0 +/
      8.0 years, N = 4) or old (74.5 +/- 7.4 years, N = 4) donors into the scaffolds,
      with or without growth factors. The patches were characterized and used for SVR
      in a rat model of myocardial infarction. Cardiac function was assessed. RESULTS:
      In vitro results showed that cells from old donors grew slower in the scaffolds.
      However, the presence of cytokines modulated the aging-related p16 gene and
      enhanced cell proliferation, converting the old cell phenotype to a young
      phenotype. In vivo studies showed that 28 days after SVR, patches seeded with
      cells from old donors did not induce functional recovery as well as patches
      seeded with young cells. However, cytokine-enhanced patches seeded with old cells
      exhibited preserved patch area, prolonged cell survival, and augmented
      angiogenesis, and rats implanted with these patches had better cardiac function.
      The patch became an elastic tissue, and the old cells were rejuvenated.
      CONCLUSIONS: This sustained-release, cytokine-conjugated system provides a
      promising platform for engineering myocardial tissue for aged patients with heart
      failure.

PMID- 23153847
TI  - Buying new soul.

PMID- 23153848
TI  - Combined subaortic and mid-ventricular obstruction with significant aortic
      stenosis diagnosed by triphasic Doppler flow pattern: multiple levels of left
      ventricular outflow tract obstruction.

PMID- 23153849
TI  - Gratitude.

PMID- 23153851
TI  - "Super-responders" and "hypo-responders": neglecting the obvious question?

PMID- 23153852
TI  - Absence of cardiovascular implantable electronic device infection in remote
      implantations demonstrated by fluorine-18 positron emission tomography.

PMID- 23153854
TI  - Live myxoma embolism.

PMID- 23153855
TI  - Methodological differences between pharmacological treatment guidelines for
      bipolar disorder: what to do for the clinicians?
AB  - OBJECTIVE: Numerous guidelines for bipolar disorder have been published. The aim
      of this article is to underline the main differences between consensus-based
      guidelines (CBG) and evidence-based guidelines (EBG) currently available for the
      management of bipolar disorder. METHODS: A literature search for guidelines
      published since 2006 was performed. A qualitative analysis was then conducted to
      compare the methodologies and the guidelines contents. RESULTS: Comparison
      between CBG and EBG found more similarities than differences. However,
      discordances were found in the first-line choice of treatment (monotherapy or
      combination, use of lamotrigine or lithium in bipolar depression), time to
      reassessment and duration of maintenance treatment, introduction as from the
      acute phase a regimen compatible with long-term use and pharmacotherapy during
      pregnancy. CONCLUSIONS: The choice of policy, whatever the methodology used, is
      up to the authors and can, therefore, depend on their interpretation of the
      available scientific evidence. Combining both methodologies (CBG and EBG) enables
      us to meet the complete definition of evidence-based medicine.

PMID- 23153856
TI  - Two-round Delphi technique for the consensual design of a paediatric
      pharmaceutical care model.
AB  - The main goal of clinical pharmacists is to improve patient care quality by
      providing individualised care. This is achieved by validating prescriptions and
      performing pharmacotherapeutic follow-up, leading to effective, safe and
      efficient drug therapy. However, there is no specific model for medication order
      validation in paediatrics addressing the distinct issues of paediatric drug use
      or the greater susceptibility of medication errors occurring in this patient
      group. For this reason we intended to design and reach consensus on a paediatric
      pharmaceutical care model by applying a two-round Delphi technique. In order to
      define the levels of complexity in reaching consensus for the model, three
      variables were taken into account: level of access to patient medical and drug
      records (partial vs. total), access to medical and nursing staff attending the
      patient (on-site vs. off-site) and the pharmacist available time (limited vs.
      adequate). In order to describe the minimum items to be included in the
      validation process at each of the three levels of complexity, we analysed the
      safety profile in the medication order prescription previously defined in an
      epidemiological study in eight hospitals with a total capacity of 1565 paediatric
      beds. A panel of experts was recruited (50 experts from 20 different hospitals)
      and the questionnaire was completed. Consensus was established at 70% of
      agreement by experts for an item. Following debate on the items that did not
      obtain consensus, a second round was performed, after which the final consensus
      model was defined. After two rounds of consultation, consensus was obtained for
      39 out of the 41 items that were surveyed. Of these, 17 were then used for the
      basic validation model (e.g. weight/age check, dose/weight check), 13 were
      implemented in the intermediate level (e.g. identification of adverse effects
      from excipients) and 9 were incorporated at advanced level (e.g. reconciliation
      at discharge for patients at risk). By applying the model, based on homogenous
      criteria for action, the clinical pharmacist's role will improve, and in turn,
      this will doubtlessly reduce drug errors through medication order validation.

PMID- 23153857
TI  - Predictors of patient-reported recovery from motor or sensory deficits two years
      after acute symptomatic lumbar disk herniation.
AB  - OBJECTIVE: To determine the prevalence of patient-reported recovery from motor or
      sensory deficits over 2 years of follow-up after acute symptomatic lumbar disk
      herniation and to identify predictors of perceived recovery. DESIGN: A
      prospective inception cohort. SETTING: An outpatient spine clinic. PATIENTS:
      Consecutive adults with lumbosacral radicular syndrome (onset <=12 weeks) due to
      symptomatic lumbar disk herniation, confirmed by magnetic resonance imaging: 95
      patients with a baseline motor deficit by physical examination and 59 patients
      with a baseline sensory deficit by physical examination. METHODS: The patients
      received individualized nonsurgical treatment or, in a minority of cases,
      surgical treatment. All of the patients underwent a standardized baseline
      neurologic examination, including motor and sensory testing. Patients with a
      motor or sensory deficit at the baseline examination reported on whether they
      perceived persisting weakness or sensory deficits at 1- and 2-year follow-up. We
      calculated the 1- and 2-year prevalence of patient-reported persisting weakness
      or sensory deficits. We examined factors associated with perceived recovery from
      motor or sensory deficits by using bivariate analyses and multivariate logistic
      regression. RESULTS: Among patients with a baseline motor deficit, the prevalence
      of patient-reported continuing weakness was 38% at 1 year and 25% at 2 years.
      Among patients with a baseline sensory deficit, the prevalence of patient
      reported continuing sensory deficits was 53% at 1 year and 47% at 2 years. A
      positive straight leg raise test (odds ratio [OR] 0.26 [95% confidence interval
      (CI) 0.08-0.83]) and opioid use (OR 0.24 [95% CI 0.06-0.83]) were independently
      and negatively predictive of patient-reported motor recovery. Female gender was
      independently and negatively predictive of patient-reported sensory recovery (OR
      0.20 [95% CI 0.04-0.99]). CONCLUSIONS: Patient-reported recovery from motor
      deficits after lumbar disk herniation occurs for 75% of patients over 2 years,
      but recovery from sensory deficits over this time frame occurs in only 53% of
      patients. A positive straight-leg raise test and female gender may predict poor
      recovery from motor and sensory deficits, respectively.

PMID- 23153858
TI  - What is evaluation of hematuria by primary care physicians? Use of electronic
      medical records to assess practice patterns with intermediate follow-up.
AB  - BACKGROUND: To determine whether patients found to have hematuria by their
      primary care physicians are evaluated according to best practice policy.
      MATERIALS AND METHODS: The University of Texas Southwestern Medical Center
      maintains institutional outpatient electronic medical records (EMR) that are used
      by all providers in all specialties. We conducted an Institutional Review Board
      approved observational study of patients found to have more than 5 red blood
      cells/high power field between March 2009 and February 2010. RESULTS: There were
      449 patients of whom the majority were female (82%), Caucasian (39%), with
      microscopic hematuria (MH) (85%). Almost 58% of patients were initially
      symptomatic with urinary symptoms or pain. Evaluation for the source of hematuria
      was limited and included imaging (35.6%), cystoscopy (9%, and cytology (7.3%).
      Only 36% of men and 8% of women were referred to a urologist. No abnormality was
      found in 32% and 51% of patients with gross hematuria and MH, respectively (P =
      0.004). There were 4 bladder tumors and 1 renal mass detected. Male gender,
      ethnicity and gross (vs. microscopic) hematuria were associated with higher rate
      of urological referral. Advanced age, smoking, provider practice type, and the
      presence of urinary symptoms were not associated with an increase rate of
      urological referral. No additional cancers were diagnosed with 29-month follow
      up. CONCLUSIONS: While urinalysis remains a common diagnostic tool, most cases of
      both microscopic and gross hematuria are not fully evaluated according to
      guidelines. Use of cystoscopy, cytology, and upper tract imaging is limited.
      Further studies will be needed to determine the extent of the problem and impact
      on morbidity and survival.

PMID- 23153859
TI  - Serum levels of chromogranin A are not predictive of high-grade, poorly
      differentiated prostate cancer: results from an Italian biopsy cohort.
AB  - OBJECTIVES: To explore the association of chromogranin A (CgA) levels and the
      risk of poorly differentiated prostate cancer (CaP) in men undergoing prostate
      biopsy. MATERIALS AND METHODS: Between 2006 and 2012, we prospectively enrolled
      1,018 men with no history of CaP undergoing prostate biopsy. The risk of
      detecting poorly differentiated CaP as a function of CgA concentration was
      evaluated using crude and adjusted logistic regressions. Further analyses were
      performed to determine whether CgA was a significant predictor of high-grade CaP
      in men with low PSA (<10 ng/ml). RESULTS: We found a significantly higher level
      of CgA in men with poorly differentiated CaP. CgA was however co-linear with age,
      and serum CgA levels were not significantly associated with the overall risk of
      CaP, and the specific risk of poorly differentiated CaP (OR 1.001 95% CI 0.99
      1.01, P = 0.74). Moreover, in men with low PSA levels (<10 ng/ml), CgA was not a
      significant predictor of high grade-disease on univariate (OR 1.00; 95% CI 0.99
      1.01; P = 0.66) and multivariate analysis (P = 0.85). CONCLUSIONS: In our cohort
      of patients, the serum level of CgA is not a significant predictor of poorly
      differentiated CaP on initial prostate biopsy, even in men with low PSA levels
      (<10 ng/ml). According to our experience, CgA should not be considered a reliable
      marker to predict poorly differentiate cancer in the setting of initial prostate
      biopsy.

PMID- 23153860
TI  - An investigation into the adsorption of thorium(IV) from aqueous solutions by a
      carboxylate-functionalised graft copolymer derived from titanium dioxide
      densified cellulose.
AB  - The use of a carboxylate-functionalized graft copolymer (PGTDC-COOH) based on
      titanium dioxide-densified cellulose (TDC) for the removal and recovery of
      thorium(IV) [Th(IV)] from industrial wastewater is reported in this paper.
      Infrared spectroscopy and X-ray diffractometer were used to characterize the
      adsorbent material. Batch equilibrium experiments showed that the adsorbent
      exhibited 98.6 +/- 3.1% adsorption from an initial concentration of 10 mg/L
      Th(IV) solution at pH 5.0. The sorption kinetics have been analysed by pseudo
      first-order and pseudo-second-order kinetic models and the adsorption kinetics
      was described by pseudo-second-order model. The experimental data obeyed Langmuir
      isotherm and the maximum monolayer adsorption capacity for Th(IV) was also found
      to be 92.23 +/- 2.4 mg/g at 30  degrees C. The desorption capacity of HCl
      concentrations of different strengths ranging from 0.001 to 0.1 M was also
      studied. Maximum desorption of 98.2 +/- 2.8% for Th(IV) occurred with 0.1 M HCl.
      The adsorption efficiency towards Th(IV) ion removal was tested using artificial
      sea water. Almost complete removal was possible with 3.5 g of the adsorbent from
      1 L of the sea water.

PMID- 23153861
TI  - Natural radioactivity determination in samples of Peperomia pellucida commonly
      used as a medicinal herb.
AB  - The concentration of (238)U, (232)Th, (230)Th, (226)Ra, (228)Ra and (210)Pb were
      determined in samples of Peperomia pellucida and in the surrounding soil, by
      alpha spectrometry and gross alpha and beta counting. The radionuclide activity
      concentrations ranged from 4.3 to 38 Bq kg(-1), 1.7-124 Bq kg(-1), 2.1-38 Bq kg(
      1), 8.5-37 Bq kg(-1), 3.2-46 Bq kg(-1), 39-93 Bq kg(-1), respectively. In the
      plant extractions and infusions as used for consumption, the mean recoveries were
      from 23% to 60% in maceration and 24-75% in infusion.

PMID- 23153862
TI  - Impact of a dedicated cancer center surveillance program on guideline adherence
      for patients with stage II and III colorectal cancer.
AB  - Surveillance after curative treatment for stage II/III colorectal cancer
      identifies surgically resectable disease and improves survival. We evaluated
      adherence to guidelines and outcomes for 408 patients enrolled in an innovative
      follow-up program at our cancer center. We found that a dedicated intensive
      surveillance program can impact adherence to guidelines for patients with
      colorectal cancer. BACKGROUND: Our aims were to evaluate adherence to guidelines
      on colorectal cancer surveillance and outcomes for patients enrolled in an
      innovative follow-up program at our cancer center. PATIENTS AND METHODS: A
      retrospective chart review was conducted at the Cross Cancer Institute in
      Edmonton, Canada. Patients with stage II/III colorectal cancer who completed
      treatment and who entered into the program from December 1, 2007, to December 31,
      2009, were identified. The minimum standard of care follow-up was defined as (1)
      carcinoembryonic antigen (CEA) testing every 120 days for 3 years; (2) computed
      tomography of chest, abdomen, and pelvis at 10 to 14 months and 22 to 26 months
      after surgery; and (3) colonoscopy within 14 months of surgery. RESULTS: A total
      of 408 patients met inclusion criteria. Two hundred (49.0%) patients were
      adherent to all 3 components of surveillance. Among all patients, 57 (14.0%) were
      nonadherent to computed tomography imaging, 135 (33.1%) were nonadherent to
      colonoscopy, and 96 (23.5%) were nonadherent to CEA testing. Determinants of
      nonadherence are described. In total, 192 (47.2%) patients had an abnormal
      surveillance investigation that led to 307 follow-up events. After a median of
      1.6 years, 69 (16.9%) patients had documented tumor recurrence. Sixty-one (88.4%)
      of these 69 patients had recurrence diagnosed via surveillance, and 31 (44.9%)
      patients were considered potentially resectable. CONCLUSIONS: Our study
      demonstrated an improvement in CEA testing since the program began; however,
      adherence rates for all components are not yet optimal. Alterations to
      surveillance program management are outlined. Further investigation will
      determine whether intense follow-up improves patient survival locally.

PMID- 23153863
TI  - Pediatric ischemic stroke: acute management and areas of research.

PMID- 23153864
TI  - Patterns of catch-up growth.

PMID- 23153865
TI  - Response to letter to the editor: "support for burn splint research".

PMID- 23153866
TI  - Autograft fat in neurological surgery.

PMID- 23153867
TI  - Utility of magnetization transfer T1 imaging in children with seizures.
AB  - Failure to detect FCD and similar lesions encountered in patients with tuberous
      sclerosis can have significant clinical consequences, such as preventing surgical
      intervention for medically refractory epilepsy and misguiding prognostic
      information regarding cognitive development. Here, we show the beneficial effects
      on detection of FCD and cortical tubers when using a magnetization transfer T1
      sequence for children with seizures who underwent MR imaging at our institution.

PMID- 23153868
TI  - Effect of patient sex on white matter alterations in unilateral medial temporal
      lobe epilepsy with hippocampal sclerosis assessed by diffusion tensor imaging.
AB  - BACKGROUND AND PURPOSE: Studies shows ictal behavior and symptoms are affected by
      patient sex in temporal lobe epilepsy. The purpose of our study was to determine
      whether alterations in the WM as assessed by DTI display different patterns in
      male and female patients with unilateral HS. MATERIALS AND METHODS: Patients with
      unilateral HS were categorized as women with right HS (n=12), men with right HS
      (n=10), women with left HS (n=12), and men with left HS (n=10). DTI of the brain
      along 64 noncollinear directions was obtained from 44 patients and 37 sex-matched
      control participants. We used TBSS to analyze whole-brain WM. Regions with
      significant changes of FA and MD, and their mean FA, MD, total number of
      significant voxels, and asymmetry indices were determined for each group.
      RESULTS: All groups showed bilateral and extensive reductions of FA and elevated
      MD in the WM, more prominent ipsilateral to the affected hippocampus. The total
      number of voxels with decreased FA in patients compared with that of control
      participants was higher in women with right HS (24,727 vs 5,459) and in men with
      left HS (27,332 vs 14,013) than in their counterparts. Changes in MD associated
      with right HS were more extensive in both men and women (right vs left HS, women:
      16,926 vs 5,458; men: 5,389 vs 4,764) than in those with left HS. In patients
      with right HS, the ipsilateral cingulum, uncinate fasciculus, internal and
      external capsules, and right acoustic radiation were involved extensively in
      women. CONCLUSIONS: Women and men showed different patterns in extent of WM
      alterations associated with HS.

PMID- 23153870
TI  - Thrombosis heralding aneurysmal rupture: an exploration of potential mechanisms
      in a novel giant swine aneurysm model.
AB  - BACKGROUND AND PURPOSE: The relationship between aneurysm dimensions, flow,
      thrombosis, and rupture remains poorly understood. We attempted to clarify this
      relationship by exploring various swine aneurysm models. MATERIALS AND METHODS:
      Bilateral carotid aneurysms were constructed according to 3 protocols in 24
      animals: small aneurysms with wide necks (group 1; n = 6 animals); small
      aneurysms with small necks (group 2; n = 4 animals), and giant aneurysms with
      large necks (group 3; n = 14 animals). Group 3 included 3 subgroups, related to
      testing the model in various experimental conditions: The neck was clipped in 3
      animals; venous pouches lacked an endothelial lining in 4 animals; and 7 were
      control animals. Animals were followed until rupture, or for 1-4 weeks.
      Angiography was performed postoperatively and before euthanasia. We studied
      lesion pathology, paying attention to thrombosis, recanalization, wall
      composition, and perianeurysmal hemorrhage. RESULTS: Groups differed
      significantly in aneurysm dimensions and aspect ratio (P = .002). Ruptures
      occurred more frequently in animals with untreated giant aneurysms (7/7) than in
      animals with small wide-neck (0/6) or small-neck (2/4) aneurysms (P = .002).
      Ruptures occurred only in animals with thrombosed aneurysms. Lesions lacking an
      endothelial lining and 5 of 6 clipped venous pouches thrombosed but did not
      rupture. One giant lesion ruptured despite complete clipping. The wall was
      deficient in alpha-actin and was infiltrated with inflammatory cells and
      erythrocytes in all thrombosed cases, ruptured or not. Ruptures were associated
      with recanalizing channels in 9 of 10 cases. CONCLUSIONS: Thrombosis,
      inflammation, and recanalization may precipitate aneurysmal ruptures in a swine
      model.

PMID- 23153869
TI  - Insula and orbitofrontal cortical morphology in substance dependence is modulated
      by sex.
AB  - BACKGROUND AND PURPOSE: Frontolimbic circuits are involved in learning and
      decision-making processes thought to be affected in substance-dependent
      individuals. We investigated frontolimbic cortical morphometry in substance
      dependent men and women and determined whether morphometric measurements
      correlated with decision-making performance. MATERIALS AND METHODS: Twenty-eight
      abstinent SDI (17 men/11 women) were compared with 28 controls (13 men/15 women).
      Cortical thicknesses and volumes were computed by using FreeSurfer. After
      controlling for age and intracranial volume, group and sex effects were analyzed
      in 3 a priori regions of interest: the insula, orbitofrontal cortex, and anterior
      cingulate cortex by using analysis of covariance. A secondary whole-brain
      analysis was conducted to verify region-of-interest results and to explore
      potential differences in other brain regions. RESULTS: Region-of-interest
      analyses revealed a main effect of group on the left insula cortex, which was
      thinner in SDI compared with controls (P = .02). There was a group by sex
      interaction on bilateral insula volume (left, P = .02; right, P = .001) and right
      insula cortical thickness (P = .007). Compared with same-sex controls, female SDI
      had smaller insulae, whereas male SDI had larger insulae. Neither ACC nor OFC
      significantly differed across group. Performance on a decision-making task was
      better in controls than SDI and correlated with OFC measurements in the controls.
      CONCLUSIONS: SDI and controls differed in insula morphology, and those
      differences were modulated by sex. No group differences in OFC were observed, but
      OFC measurements correlated with negative-reinforcement learning in controls.
      These preliminary results are consistent with a hypothesis that frontolimbic
      pathways may be involved in behaviors related to substance dependence.

PMID- 23153871
TI  - CT fluoroscopy-guided cervical interlaminar steroid injections: is it overkill?

PMID- 23153872
TI  - How to value technological innovation: a proposal for determining relative
      clinical value.

PMID- 23153873
TI  - Two patients with a solitary fibrous tumor of the thoracic spinal cord.
AB  - We report two patients with thoracic spinal solitary fibrous tumor (SFT). This
      report includes a patient with the first secondary SFT arising in the central
      nervous system from a pleural origin to our knowledge. The diagnosis was
      confirmed by histological and immunohistochemical analysis. Both patients
      underwent gross total resection of their tumors and did not show signs of local
      recurrence. The patient with the secondary lesion later presented with visceral
      dissemination. We review the reports of spinal SFT and discuss the diagnosis and
      therapeutic management of this intriguing entity.

PMID- 23153874
TI  - Patient safety in the critical care environment.
AB  - Improving the quality and safety of intensive care unit (ICU) care in the United
      States is a significant challenge for the future. Obtaining improvement in
      systems of care is difficult given the reactionary mode physicians tend to enter
      when dealing with moment-to-moment crises. It will be important to implement
      quality and safety measures that are already supported by evidence. Improvement
      of device safety will be critical to reducing the large number of device-related
      complications that occur in US ICUs. Prospective collection of adverse events
      with rigorous analysis will be important to allow systematic errors to be exposed
      and corrected.

PMID- 23153875
TI  - Monitoring devices in the intensive care unit.
AB  - Monitors in the intensive care unit are imperative to taking adequate care of
      these critically ill patients. Cardiovascular, pulmonary, and neurologic monitors
      are key to performing these tasks. This article gives an overview of the most
      common monitors that are used in the intensive care unit.

PMID- 23153876
TI  - Hypovolemic shock resuscitation.
AB  - Several changes in the way patients with hemorrhagic shock are resuscitated have
      occurred over the past decades, including permissive hypotension, minimal
      crystalloid resuscitation, earlier blood transfusion, and higher plasma and
      platelet-to-red cell ratios. Hemostatic adjuncts, such as tranexamic acid and
      prothrombin complex, and the use of new methods of assessing coagulopathy are
      also being incorporated into resuscitation of the bleeding patient. These ideas
      have been incorporated by many trauma centers into institutional massive
      transfusion protocols, and adoption of these protocols has resulted in
      improvements in mortality and morbidity. This article discusses each of these new
      resuscitation strategies and the evidence supporting their use.

PMID- 23153877
TI  - Epidemiology of sepsis in surgical patients.
AB  - Sepsis in the surgical patient continues to be a common and potentially lethal
      problem. Early identification of patients and timely implementation of evidence
      based therapies continue to represent significant clinical challenges for care
      providers. The implementation of a sepsis screening program in conjunction with
      protocol for the delivery of evidence-based care and rapid source control can
      improve patient outcomes. The article provides definitions and guidelines for the
      screening and management of sepsis and septic shock.

PMID- 23153878
TI  - The value of critical care.
AB  - The primary focus of this review is on the cost-effectiveness of critical care.
      The rapid growth in health care expenditures has engendered careful scrutiny of
      the practice of medicine with regard not only to effectiveness but also to
      efficiency. This shift necessitates that physicians understand the effectiveness
      of their interventions and the cost at which this effectiveness is obtained. Cost
      effectiveness and cost-utility analyses have become crucial evaluative tools in
      medicine. Explicit articulation of comparative cost-effectiveness facilitates the
      allocation of limited resources. Physicians and policy-makers must evaluate such
      studies with caution, skepticism, and attention to the methods used.

PMID- 23153879
TI  - Mechanical ventilation.
AB  - The treatment of respiratory failure requiring mechanical ventilation has
      advanced significantly over the last 20 years. The goal of therapy in patients
      with acute respiratory distress syndrome should be to optimize oxygenation while
      minimizing the risk of ventilator-induced lung injury and providing adequate
      ventilation. Appropriate use of ventilation modes and strategies, positive-end
      expiratory pressure levels, and recruitment maneuvers can improve oxygen
      delivery. Salvage therapies, such as prone positioning, inhaled epoprostenol and
      nitric oxide, and high-frequency oscillatory ventilation, have a well-established
      role in supportive management and are associated with improved oxygenation but
      not survival.

PMID- 23153880
TI  - Removing the critically ill patient from mechanical ventilation.
AB  - Weaning from mechanical ventilation is usually straightforward but is
      occasionally challenging. Sedation must be used at the appropriate times and with
      appropriate dosing. A protocol that calls for a daily sedation holiday with a
      spontaneous breathing trial decreases time on the ventilator. Early tracheostomy
      is beneficial in traumatic brain injury patients. Noninvasive ventilation is most
      useful in patients with baseline obstructive sleep apnea and chronic obstructive
      pulmonary disease.

PMID- 23153881
TI  - Enteral nutrition in the critically ill patient.
AB  - Timing and route of nutrition provided to critically ill patients can affect
      their outcome. Early enteral nutrition has been shown to decrease specifically
      infectious morbidity in the critically ill patient. There is a small group of
      patients who are malnourished on arrival to the intensive care unit and in these
      patients parenteral nutrition is beneficial.

PMID- 23153882
TI  - Renal management in the critically ill patient.
AB  - Acute kidney injury is common in the hospital setting and morbidity and mortality
      outcomes depend on early recognition and early intervention. Identifying patients
      at risk of acute kidney injury is critical in prevention, early identification,
      and appropriate treatment.

PMID- 23153883
TI  - Common complications in the critically ill patient.
AB  - Critically ill patients in intensive care units are subject to many complications
      associated with therapy. Many of these complications are health care-associated
      infections and are related to indwelling devices, including ventilator-associated
      pneumonia, central line-associated bloodstream infection, catheter-associated
      urinary tract infection; surgical site infection, venous thromboembolism, deep
      venous thrombosis, and pulmonary embolus are other common complications. All
      efforts should be undertaken to prevent these complications in surgical critical
      care, and national efforts are under way for each of these complications. In this
      article, epidemiology, risk factors, diagnosis, treatment, and prevention of
      these complications in critically ill patients are discussed.

PMID- 23153884
TI  - Heparin-induced thrombocytopenia.
AB  - This article deals with heparin-induced thrombocytopenia. It discusses the
      pathophysiology of the disease, as well as the diagnostic challenges and
      therapeutic management. The incidence of the disease and screening
      recommendations are reviewed. The article also emphasizes the importance of
      correct diagnosis and treatment options. This article is intended for surgeons in
      all specialties and levels of training.

PMID- 23153885
TI  - Optimizing drug therapy in the surgical intensive care unit.
AB  - This article provides a review of commonly prescribed medications in the surgical
      ICU, focusing on sedatives, antipsychotics, neuromuscular blocking agents,
      cardiovascular agents, anticoagulants, and antibiotics. A brief overview of
      pharmacology is followed by practical considerations to aid prescribers in
      selecting the best therapy within a given category of drugs to optimize patient
      outcomes.

PMID- 23153886
TI  - Pain management in the ICU.
AB  - Pain management in the intensive care unit (ICU) is a complex process. Both the
      experience of pain as well as its treatment can have consequences relating to the
      overall outcome of the patient. Further, lack of the ability of many patients in
      the ICU to communicate their distress makes it even more critical for the ICU
      practitioner to understand the typical causes of pain in this setting and the
      applicability of many pain management regimens.

PMID- 23153887
TI  - Family engagement regarding the critically ill patient.
AB  - The Institute of Medicine strongly recommends a health care system that supports
      family members. Nowhere is the need for family-centered care greater than with
      critically ill patients. Simplistically, family-centered care is primarily about
      communication. Unfortunately, family perception of communication in the intensive
      care unit (ICU) is quite poor. This article reviews some strategies to improve
      communication, including family meetings and family presence at resuscitation. It
      also highlights some of the areas within the realm of ICU care in which family
      engagement is particularly important, including advance directives, end-of-life
      care, brain death, and organ donation.

PMID- 23153889
TI  - A case study in intra-abdominal sepsis.
AB  - Intra-abdominal infections are a common problem for the general surgeon and major
      sources of morbidity and mortality in the intensive care unit. Some of these
      patients present with peritonitis that can rapidly progress to septic shock. The
      basic principles of care include prompt resuscitation, antibiotics, and source
      control. This article will use a detailed case study to outline the management of
      a patient with severe intra-abdominal infection from diverticulitis from initial
      resuscitation to reconstruction. Components of the Surviving Sepsis Campaign as
      they pertain to surgical patients are discussed and updated, and the concept of
      damage control general surgery is applied.

PMID- 23153888
TI  - A case study of a multiply injured patient.
AB  - Initial evaluation of severely injured patients requires an organized, rapid, and
      thorough evaluation of the patient where life-threatening injuries are identified
      and treated simultaneously. A case study provides the basis for discussion of the
      management of the multiply injured trauma patient. The ultimate goal in
      rehabilitation of a multiply injured patient is to return each patient to as much
      independent function and ability to contribute to society as possible.

PMID- 23153890
TI  - Two case studies of cardiopulmonary effects of intra-abdominal hypertension.
AB  - Intra-abdominal hypertension falsely elevates the pulmonary artery pressure.
      Volumetric pulmonary artery catheter monitoring is an optionfor estimating
      preload in this condition. Treatment of intra-abdominal hypertension begins with
      medical therapy but once abdominal compartment syndrome develops it requires
      decompressive laparotomy for definitive management. Pulmonary hypertension
      reduces cardiac function which may be improved with inotropes that simultaneously
      reduce pulmonary artery pressure. Oxygenation may be improved with elevated PEEP
      and FiO(2).

PMID- 23153891
TI  - Surgical critical care.

PMID- 23153892
TI  - Surgical critical care.

PMID- 23153893
TI  - Social dysfunction in first-episode psychosis and relations to neurocognition,
      duration of untreated psychosis and clinical symptoms.
AB  - Signs of social dysfunction are present early in the course of psychotic
      disorders. There is a lack of knowledge about how premorbid function, illness
      history, psychotic symptoms and neurocognitive characteristics are related to
      social function in patients with first episode psychosis (FEP). The relationship
      between these factors could provide important information about the
      psychopathology underlying social dysfunction and have implications for future
      prevention and treatment efforts. Our objective is to identify early predictors
      of social functioning in patients with FEP. We examined 166 patients and 166 age-
      and gender-matched healthy controls (HC). We used a validated and comprehensive
      measure of social functioning (the Social Functioning Scale), a comprehensive
      neurocognitive test battery, in addition to measures of psychotic symptoms,
      duration of untreated psychosis (DUP) and premorbid adjustment (the Premorbid
      Adjustment Scale). Lower childhood level of social adjustment and lower
      psychomotor speed had the strongest influence across measures of social
      functioning while symptoms and DUP had a weaker influence. The main result of the
      current study is that premorbid social adjustment and psychomotor speed had the
      strongest association with measures of social functioning in patients with FEP.

PMID- 23153894
TI  - Relevance of serum copper elevation induced by oral contraceptives: a meta
      analysis.
AB  - BACKGROUND AND STUDY DESIGN: It is well documented that copper (Cu) blood levels
      are elevated in combination oral contraceptive (COC) users. The aim of this study
      was to establish the range of Cu increase in OC users compared to nonusers
      through a systematic literature overview and quantitative data analysis. RESULTS:
      Twenty-six articles were included in the meta-analysis. The increase in Cu level
      exponentially decreased in COC users over time, with a rapid decline through the
      1960s and 1970s. After controlling for the publication year, use of COC increases
      the mean serum/plasma Cu level by 0.57 mg/L (95% confidence interval 0.49-0.66
      mg/L). CONCLUSION: COCs commonly raise serum Cu to levels between 1.5 and 2 mg/L,
      which are above reference levels. Although these levels are not considered toxic,
      there are suggestions that such Cu increase could be implicated in oxidative
      pathophysiological processes in the body. Further research on safety of COCs use,
      including oxidative-stress-related effects, is warranted.

PMID- 23153895
TI  - Revitalizing long-acting reversible contraceptives in settings with high unmet
      need: a multicountry experience matching demand creation and service delivery.
AB  - BACKGROUND: Contraception in many developing countries is characterized by high
      unmet need, irregular access, low utilization and presumed demand for long-acting
      reversible contraceptives (LARCs). STUDY DESIGN: A 13-country initiative focused
      on increasing consumer demand and high quality services for intrauterine devices
      (IUDs) began in 2009. Services were provided through (a) private sector
      franchised or affiliated clinics; (b) providers seconded to the public sector and
      (c) special "event" days. Client intake data are used to compare the profile of
      IUD acceptors with IUD users from representative national datasets of select
      countries, as well as examine trends in IUD uptake. RESULTS: During 2009-2010,
      575,601 IUDs were inserted across the 13 countries. Compared to national IUD
      users, users in this project were slightly younger and less educated. Among IUD
      acceptors, 24% used no modern method at the time of IUD initiation, and 28%
      reported injectable use in the three previous months. CONCLUSIONS: Convenient,
      quality, affordable services with demand creation can result in significant
      uptake of LARCs in settings with low use.

PMID- 23153896
TI  - Fertility goal-based counseling increases contraceptive implant and IUD use in
      HIV-discordant couples in Rwanda and Zambia.
AB  - BACKGROUND: HIV-discordant heterosexual couples are faced with the dual challenge
      of preventing sexual HIV transmission and unplanned pregnancies with the
      attendant risk of perinatal HIV transmission. Our aim was to examine uptake of
      two long-acting reversible contraceptive (LARC) methods--intrauterine devices
      (IUD) and hormonal implants--among HIV-discordant couples in Rwanda and Zambia.
      STUDY DESIGN: Women were interviewed alone or with their partner during routine
      cohort study follow-up visits to ascertain fertility goals; those not pregnant,
      not infertile, not already using LARC, and wishing to limit or delay fertility
      for >=3 years were counseled on LARC methods and offered an IUD or implant on
      site. RESULTS: Among 409 fertile HIV-discordant Rwandan women interviewed (126
      alone, 283 with partners), 365 (89%) were counseled about LARC methods, and 130
      (36%) adopted a method (100 implant, 30 IUD). Of 787 fertile Zambian women
      interviewed (457 alone, 330 with partners), 528 (67%) received LARC counseling,
      of whom 177 (34%) adopted a method (139 implant, 38 IUD). In both countries, a
      woman's younger age was predictive of LARC uptake. LARC users reported fewer
      episodes of unprotected sex than couples using only condoms. CONCLUSIONS:
      Integrated fertility goal-based family planning counseling and access to LARC
      methods with reinforcement of dual-method use prompted uptake of IUDs and
      implants and reduced unprotected sex among HIV-discordant couples in two African
      capital cities.

PMID- 23153897
TI  - The effect of immediate postpartum depot medroxyprogesterone on early
      breastfeeding cessation.
AB  - BACKGROUND: This study evaluated the effect of immediate postpartum depot
      medroxyprogesterone (DMPA) on breastfeeding cessation within 6 weeks postpartum.
      STUDY DESIGN: At low-income-serving obstetric and pediatric clinics, eligible
      mothers within 1 year postpartum were recruited to participate in a retrospective
      cohort study. The 183 participants completed a self-administered survey. Surveys
      were merged with birth certificate data and perinatal maternal/infant medical
      records. Kaplan-Meier distributions assessed the relationship between DMPA use
      and breastfeeding cessation. A multivariable Cox proportional hazards model
      estimated hazard ratios (HRs) and included five known risk factors (age,
      education, race, parity and parental cohabitation) and identified potential
      confounders. RESULTS: Consistent with the biologic model, the Kaplan-Meier
      results raised the possibility of a detrimental effect of DMPA on duration of any
      breastfeeding, but differences in these distributions did not achieve statistical
      significance (p=.24); after adjustment for potential confounders, this
      nonstatistically significant association remained (HR: 1.22; confidence interval:
      0.75-1.98). CONCLUSION: Given the state of the evidence, it is unclear whether a
      causal effect does or does not exist. However, if there is a causal effect of
      DMPA on breastfeeding duration, it is minimal. Additional well-designed research
      is warranted.

PMID- 23153898
TI  - Prolonged monitoring of ethinyl estradiol and levonorgestrel levels confirms an
      altered pharmacokinetic profile in obese oral contraceptives users.
AB  - BACKGROUND: Pharmacokinetic (PK) parameters based on short sampling times (48 h
      or less) may contain inaccuracies due to their dependency on extrapolated values.
      This study was designed to measure PK parameters with greater accuracy in obese
      users of a low-dose oral contraceptive (OC) and to correlate drug levels with
      assessments of end-organ activity. STUDY DESIGN: Obese [body mass index (BMI)
      >=30 kg/m2], ovulatory, otherwise healthy women (n=32) received an OC containing
      20 mcg ethinyl estradiol (EE)/100 mcg levonorgestrel (LNG) for two cycles. EE and
      LNG PK parameters were characterized for 168 h at the end of Cycle 1. During
      cycle 2, biweekly outpatient visits were performed to assess cervical mucus,
      monitor ovarian activity with transvaginal ultrasound and obtain serum samples to
      measure EE, LNG, estradiol and progesterone levels. PK parameters were calculated
      and correlated with end-organ activity and compared against control samples
      obtained from normal and obese women sampled up to 48 h in a previous study.
      Standard determination of PK accuracy was performed, defined by the dependency on
      extrapolated values ('excess' area under the curve of 25% or less). RESULTS: The
      mean BMI was 39.4 kg/m2 (SD 6.6) with a range of 30-64 kg/m2. Key LNG PK
      parameters were as follows: clearance, 0.52 L/h (SD 0.24); half-life, 65 h (SD
      40); area under the curve (AUC), 232 h*ng/mL (SD 102); and time to reach steady
      state, 13.6 days (SD 8.4). The majority of subjects had increased ovarian
      activity with diameter of follicles >=8 mm (n=25), but only seven women had
      follicles >=10 mm plus cervical mucus scores >=5. Evidence of poor end-organ
      suppression did not correlate with the severity of the alterations in PK. As
      compared to historical normal and obese controls (48-h PK sampling), clearance,
      half-life, AUC and time to reach steady state were found to be significantly
      different (p<=.05) in obese women undergoing a longer duration of PK sampling
      (168 h). Longer sampling also improved PK accuracy for obese women (excess AUC
      20%) as compared to both normal and obese controls undergoing shorter sampling
      times (48 h) with excess AUCs of 25% and 50%, respectively. CONCLUSIONS: Obesity
      results in significant alterations in OC steroid PK parameters, but the severity
      of these alterations did not correlate with end-organ suppression. A longer PK
      sampling interval (168 h vs. 48 h) improved the accuracy of PK testing.

PMID- 23153899
TI  - Calculating contraceptive decisions while intoxicated.
AB  - BACKGROUND: Experimental research in laboratory conditions indicates that
      intoxication makes unprotected sex more favorable to subjects, while event-level
      research indicates little causal effect of intoxication on condom use. Little
      work has addressed the effect of intoxication on hormonal contraceptive use.
      STUDY DESIGN: This study analyzes in-depth interviews with 30 men and 30 women
      between the ages of 18 and 30 years on the East Coast of the United States about
      their contraceptive decisions and use. RESULTS: Respondents believed that
      frequent intoxication discouraged condom use and consistent contraceptive pill
      taking. Their accounts suggested that intoxication discouraged calculated
      contraceptive decision-making, and consequently, they mostly reverted to their
      standard contraceptive habits. People who were consistent contraceptors sober
      were usually consistent contraceptors while intoxicated, and people who were
      inconsistent contraceptors sober were usually inconsistent contraceptors while
      intoxicated. This pattern applied to both condom use and hormonal contraceptive
      use.

PMID- 23153901
TI  - The Quick Start Contraception Initiation Method during the 6-week postpartum
      visit: an efficacious way to improve contraception in Federally Qualified Health
      Centers.
AB  - BACKGROUND: About half of all pregnancies in the United States are unplanned, and
      many start soon after a previous delivery. Our aim was to determine if the
      implementation of the Quick Start Contraception Initiation Method during the 6
      week postpartum evaluation could improve the delivery of contraception. STUDY
      DESIGN: The medical records of 979 patients seen for their 6-week postpartum
      visit at our urban Federally Qualified Health Center (FQHC) between July 2004 and
      June 2006 were reviewed. The patients were distributed into two groups defined by
      evaluations performed prior to or after the implementation of the new
      contraception initiation method. Summary statistics and differences in the
      proportions were calculated. A probability of <.05 was considered significant.
      RESULTS: The Quick Start Contraception Initiation Method was implemented in July
      2005. Five-hundred and sixteen patients were in Group 1, and 463 patients were in
      Group 2. Demographic variables were similar among groups. Contraception delivery
      rate was 50% in Group 1 and 72% in Group 2 (p<.05). Eighty percent of patients in
      Group 1 and 76% of those in Group 2 requested contraception, and 26% of Group 1
      and 3% of Group 2 did not receive it. The improvement in dispensing contraception
      was most noticeable among teenagers. CONCLUSION: These findings suggest that the
      Quick Start Contraception Initiation Method at the time of the 6-week postpartum
      evaluation improves the delivery of contraception in FQHCs.

PMID- 23153900
TI  - Randomized comparison of two Internet-supported fertility-awareness-based methods
      of family planning.
AB  - BACKGROUND: The aim was to compare the efficacy and acceptability of two Internet
      supported fertility-awareness-based methods of family planning. STUDY DESIGN: Six
      hundred and sixty-seven women and their male partners were randomized into either
      an electronic hormonal fertility monitor (EHFM) group or a cervical mucus
      monitoring (CMM) group. Both groups utilized a Web site with instructions, charts
      and support. Acceptability was assessed online at 1, 3 and 6 months. Pregnancy
      rates were determined by survival analysis. RESULTS: The EHFM participants
      (N=197) had a total pregnancy rate of 7 per 100 users over 12 months of use
      compared with 18.5 for the CMM group (N=164). The log rank survival test showed a
      significant difference (p<.01) in survival functions. Mean acceptability for both
      groups increased significantly over time (p<.0001). Continuation rates at 12
      months were 40.6% for the monitor group and 36.6% for the mucus group.
      CONCLUSION: In comparison with the CMM, the EHFM method of family planning was
      more effective. All users had an increase in acceptability over time. Results are
      tempered by the high dropout rate.

PMID- 23153902
TI  - Controversies in family planning: desired pregnancy, IUD in situ and no strings
      visible.

PMID- 23153903
TI  - When can a woman start combined hormonal contraceptives (CHCs)? A systematic
      review.
AB  - BACKGROUND: Conventional methods of initiating combined hormonal contraceptives
      (CHCs), specifically combined oral contraceptives (COCs), the contraceptive patch
      and the contraceptive ring, require that women delay starting CHCs until menses
      begin, during which time a woman may be at risk of unintended pregnancy. The
      objective of this systematic review is to examine the evidence on the risk of
      becoming pregnant after starting the method (contraceptive effectiveness
      including surrogate measures such as ovarian follicular development and hormone
      levels), risk of already being pregnant, side effects and continuation when
      starting CHCs on different days of the menstrual cycle. STUDY DESIGN: We searched
      the MEDLINE database for all articles (in all languages) published in peer
      reviewed journals from inception through March 2012 for evidence relevant to
      starting CHCs on different days of the menstrual cycle and the outcomes of
      contraceptive effectiveness (including ovarian follicular development and
      hormonal levels), side effects and continuation rates. RESULTS: From 1635
      reviewed articles, 18 studies met our inclusion criteria. Evidence from four
      studies suggests that neither the risk of inadvertently starting COCs in a woman
      who is pregnant nor the risk of pregnancy after COC initiation are affected by
      the cycle day on which COCs are started. While follicular activity increased as
      the cycle day on which COCs were initiated increased, no women ovulated when
      starting on Day 5. When starting on Day 7, there was no increase in ovulation for
      a 30-mcg pill but a significant increase in ovulation with a 20-mcg pill compared
      with starting on Day 1. Evidence from two small studies suggests that 7 days of
      pills leads to inhibition of ovulation. One small study suggests that only 3 days
      of ring use is needed to inhibit ovulation, but this was following one complete
      treatment cycle of ring use. Evidence also suggests that starting CHCs on any day
      of the cycle does not affect bleeding problems or other side effects for both
      COCs and the patch. While starting CHCs via Quick Start (starting on the day of
      the health care visit) may initially increase continuation compared with more
      conventional starting strategies, evidence suggests that this difference
      disappears over time. CONCLUSION: The body of evidence suggested that (a)
      pregnancy rates did not differ by the timing of CHC initiation; (b) the more
      follicular activity that occurred prior to starting COCs, the more likely
      ovulation was to occur; however, no ovulations were seen when COCs were started
      at a follicle diameter of 10 mm (mean cycle day=7.6) or when the ring was started
      at follicle diameter of 13 mm (median cycle day=11); (c) bleeding patterns and
      other side effects did not vary with the timing of CHC initiation and (d)
      continuation rates of CHCs were initially improved by Quick Start, but
      differences between groups disappeared over time.

PMID- 23153904
TI  - Metabolomic analysis of pancreatic beta cells following exposure to high glucose.
AB  - BACKGROUND: Chronic exposure to hyperglycaemic conditions has been shown to have
      detrimental effects on beta cell function. The resulting glucotoxicity is a
      contributing factor to the development of type 2 diabetes. The objective of this
      study was to combine a metabolomics approach with functional assays to gain
      insight into the mechanism by which glucotoxicity exerts its effects. METHODS:
      The BRIN-BD11 and INS-1E beta cell lines were cultured in 25 mM glucose for 20 h
      to mimic glucotoxic effects. PDK-2 protein expression, intracellular glutathione
      levels and the change in mitochondrial membrane potential and intracellular
      calcium following glucose stimulation were determined. Metabolomic analysis of
      beta cell metabolite extracts was performed using GC-MS, 1H NMR and 13C NMR.
      RESULTS: Conditions to mimic glucotoxicity were established and resulted in no
      loss of cellular viability in either cell line while causing a decrease in
      insulin secretion. Metabolomic analysis of beta cells following exposure to high
      glucose revealed a change in amino acids, an increase in glucose and a decrease
      in phospho-choline, n-3 and n-6 PUFAs during glucose stimulated insulin secretion
      relative to cells cultured under control conditions. However, no changes in
      calcium handling or mitochondrial membrane potential were evident. CONCLUSIONS:
      Results indicate that a decrease in TCA cycle metabolism in combination with an
      alteration in fatty acid composition and phosphocholine levels may play a role in
      glucotoxicity induced impairment of glucose stimulated insulin secretion. GENERAL
      SIGNIFICANCE: Alterations in certain metabolic pathways play a role in
      glucotoxicity in the pancreatic beta cell.

PMID- 23153905
TI  - Evidence for pituitary adenylate cyclase-activating peptide as a direct
      immunoregulator in teleost head kidney.
AB  - In mammals, pituitary adenylate cyclase activating polypeptide (PACAP) is a
      potent anti-inflammatory factor, showing that it inhibits the expression and
      release of proinflammatory cytokines and enhances the production of anti
      inflammatory factors. However, whether fish PACAP plays similar regulatory roles
      as seen in mammals remains unclear. In the present study, expression of PACAP
      specific receptor PAC1-R was shown in grass carp head kidney and spleen,
      supporting that PACAP may have a direct effect on fish immune cells. To test this
      hypothesis, the immunoregulatory role of grass carp PACAP (gcPACAP) was examined
      in head kidney leucocytes (HKLs). Results showed that gcPACAP inhibited basal and
      further attenuated lipopolysaccharide (LPS)-stimulated cell viability of HKLs,
      indicating that gcPACAP may possess similar inhibitory property at cellular level
      as seen in mammals. Curiously, in vitro and in vivo studies revealed that gcPACAP
      stimulated proinflammatory factors (IL-1beta and TNF-alpha) but not IL-10 mRNA
      expression in HKLs and head kidney. Moreover, bacterial infection and LPS
      enhanced IL-1beta, TNF-alpha and IL-10 mRNA expression in grass carp head kidney
      and HKLs, respectively, and these stimulatory effects were not influenced by
      gcPACAP. These findings suggest that PACAP plays distinct roles, at least does
      not function as an anti-inflammatory factor, in fish compared with that in
      mammals.

PMID- 23153906
TI  - Coronary flow reserve during dipyridamole stress echocardiography predicts
      mortality.
AB  - OBJECTIVES: The goal of this study was to evaluate the ability of coronary flow
      reserve (CFR) over regional wall motion to predict mortality in patients with
      known or suspected coronary artery disease (CAD). BACKGROUND: CFR evaluated using
      pulsed Doppler echocardiography testing on left anterior descending artery is the
      state-of-the-art method during vasodilatory stress echocardiography. METHODS: In
      a prospective, multicenter, observational study, we evaluated 4,313 patients
      (2,532 men; mean age 65 +/- 11 years) with known (n = 1,547) or suspected (n =
      2,766) CAD who underwent high-dose dipyridamole (0.84 mg/kg over 6 min) stress
      echocardiography with CFR evaluation of left coronary descending artery (LAD) by
      Doppler. Overall mortality was the only endpoint analyzed. RESULTS: Stress
      echocardiography was positive for ischemia in 765 (18%) patients. Mean CFR was
      2.35 +/- 0.68. At individual patient analysis, 1,419 (33%) individuals had CFR
      <=2. During a median follow-up of 19 months (1st quartile 8; 3rd quartile 36),
      146 patients died. The 4-year mortality was markedly higher in subjects with CFR
      <=2 than in those with CFR >2, both considering the group with ischemia (39% vs.
      7%; p < 0.0001) and the group without ischemia at stress echocardiography (12%
      vs. 3%; p < 0.0001). At multivariable analysis, CFR on LAD <=2 (hazard ratio
      [HR]: 3.31; 95% confidence interval [CI]: 2.29 to 4.78; p < 0.0001), ischemia at
      stress echocardiography (HR: 2.40, 95% CI: 1.65 to 3.48, p < 0.0001), left bundle
      branch block (HR: 2.26, 95% CI: 1.50 to 3.41; p < 0.0001), age (HR: 1.08, 95% CI:
      1.06-1.10; p < 0.0001), resting wall motion score index (HR: 3.52, 95% CI: 2.38
      to 5.21; p < 0.0001), male sex (HR: 1.74, 95% CI: 1.12 to 2.52; p = 0.003), and
      diabetes mellitus (HR: 1.47, 95% CI: 1.03 to 2.08; p = 0.03) were independent
      predictors of mortality. CONCLUSIONS: CFR on LAD is a strong and independent
      indicator of mortality, conferring additional prognostic value over wall motion
      analysis in patients with known or suspected CAD. A negative result on stress
      echocardiography with a normal CFR confers an annual risk of death <1% in both
      patient groups.

PMID- 23153907
TI  - Coronary flow velocity reserve and survival.

PMID- 23153908
TI  - Noninvasive diagnosis of ischemia-causing coronary stenosis using CT angiography:
      diagnostic value of transluminal attenuation gradient and fractional flow reserve
      computed from coronary CT angiography compared to invasively measured fractional
      flow reserve.
AB  - OBJECTIVES: The aim of this study was to compare the diagnostic performance of
      coronary computed tomography angiography (CCTA)-derived computed fractional flow
      reserve (FFR(CT)) and transluminal attenuation gradient (TAG) for the diagnosis
      of lesion-specific ischemia. BACKGROUND: Although CCTA is commonly used to detect
      coronary artery disease (CAD), it cannot reliably assess the functional
      significance of CAD. Novel technologies based on CCTA were developed to integrate
      anatomical and functional assessment of CAD; however, the diagnostic performance
      of these methods has never been compared. METHODS: Fifty-three consecutive
      patients who underwent CCTA and coronary angiography with FFR measurement were
      included. Independent core laboratories determined CAD severity by CCTA, TAG, and
      FFR(CT). The TAG was defined as the linear regression coefficient between
      intraluminal radiological attenuation and length from the ostium; FFR(CT) was
      computed from CCTA data using computational fluid dynamics technology. RESULTS:
      Among 82 vessels, 32 lesions (39%) had ischemia by invasive FFR (FFR <=0.80).
      Sensitivity, specificity, positive and negative predictive values, and positive
      and negative likelihood ratio of TAG (<= -0.654 HU/mm) for detection of ischemia
      were 38%, 88%, 67%, 69%, 3.13, and 0.71, respectively; and those of FFR(CT) were
      81%, 94%, 90%, 89%, 13.54, and 0.20, respectively. Receiver-operating
      characteristic curve analysis showed a significantly larger area under the curve
      (AUC) for FFR(CT) (0.94) compared to that for TAG (0.63, p < 0.001) and CCTA
      stenosis (0.73, p < 0.001). In vessels with noncalcified plaque or partially
      calcified plaque, FFR(CT) showed a larger AUC (0.94) compared to that of TAG
      (0.63, p < 0.001) or CCTA stenosis (0.70, p < 0.001). In vessels with calcified
      plaque, AUC of FFR(CT) (0.92) was not statistically larger than that of TAG
      (0.75, p = 0.168) or CCTA stenosis (0.80, p = 0.195). CONCLUSIONS: Noninvasive
      FFR computed from CCTA provides better diagnostic performance for the diagnosis
      of lesion-specific ischemia compared to CCTA stenosis and TAG.

PMID- 23153909
TI  - Combined CT coronary angiography and stress myocardial perfusion imaging for
      hemodynamically significant stenoses in patients with suspected coronary artery
      disease: a comparison with fractional flow reserve.
AB  - OBJECTIVES: We sought to determine the accuracy of combined coronary computed
      tomography angiography (CTA) and computed tomography stress myocardial perfusion
      imaging (CTP) in the detection of hemodynamically significant stenoses using
      fractional flow reserve (FFR) as a reference standard in patients with suspected
      coronary artery disease. BACKGROUND: CTP can be qualitatively assessed by visual
      interpretation or quantified by the transmural perfusion ratio determined as the
      ratio of subendocardial to subepicardial contrast attenuation. The incremental
      value of each technique in addition to coronary CTA to detect hemodynamically
      significant stenoses is not known. METHODS: Forty symptomatic patients underwent
      FFR and 320-detector computed tomography assessment including coronary CTA and
      CTP. Myocardial perfusion was assessed using the transmural perfusion ratio and
      visual perfusion assessment. Computed tomography images were assessed by
      consensus of 2 observers. Transmural perfusion ratio <0.99 was used as the
      threshold for abnormal perfusion. FFR <=0.8 indicated hemodynamically significant
      stenoses. RESULTS: Coronary CTA detected FFR-significant stenoses with 95%
      sensitivity and 78% specificity. The additional use of visual perfusion
      assessment and the transmural perfusion ratio both increased the specificity to
      95%, with sensitivity of 87% and 71%, respectively. The area under the receiver
      operating characteristic curve for coronary CTA + visual perfusion assessment was
      significantly higher than both coronary CTA (0.93 vs. 0.85, p = 0.0003) and
      coronary CTA + the transmural perfusion ratio (0.93 vs. 0.79, p = 0.0003). Per
      vessel and per-patient accuracy for coronary CTA, coronary CTA + the transmural
      perfusion ratio, and coronary CTA + visual perfusion assessment was 83% and 83%,
      87% and 92%, and 92% and 95%, respectively. CONCLUSIONS: In suspected coronary
      artery disease, combined coronary CTA + CTP identifies patients with
      hemodynamically significant stenoses with >90% accuracy compared with FFR. When
      interpreted with coronary CTA, visual perfusion assessment provided superior
      incremental value in the detection of FFR-significant stenoses compared with the
      quantitative transmural perfusion ratio assessment.

PMID- 23153910
TI  - The one-stop shop offering both coronary anatomy and myocardial perfusion: may
      well be opening soon, around the corner.

PMID- 23153912
TI  - Are trabeculae and papillary muscles an integral part of cardiac anatomy: or
      annoying features to exclude while tracing endocardial boundaries?

PMID- 23153911
TI  - Correlation of trabeculae and papillary muscles with clinical and cardiac
      characteristics and impact on CMR measures of LV anatomy and function.
AB  - OBJECTIVES: The goal of this study was to assess the relationship of left
      ventricular (LV) trabeculae and papillary muscles (TPM) with clinical
      characteristics in a community-based, free-living adult cohort and to determine
      the effect of TPM on quantitative measures of LV volume, mass, and ejection
      fraction (EF). BACKGROUND: Hypertrabeculation has been associated with adverse
      cardiovascular events, but the distribution and clinical correlates of the volume
      and mass of the TPM in a normal left ventricle have not been well characterized.
      METHODS: Short-axis cine cardiac magnetic resonance images, obtained using a
      steady-state free precession sequence from 1,494 members of the Framingham Heart
      Study Offspring cohort, were analyzed with software that automatically segments
      TPM. Absolute TPM volume, TPM as a fraction of end-diastolic volume (EDV)
      (TPM/EDV), and TPM mass as a fraction of LV mass were determined in all offspring
      and in a referent group of offspring free of clinical cardiovascular disease and
      hypertension. RESULTS: In the referent group (mean age 61 +/- 9 years; 262 men
      and 423 women), mean TPM was 23 +/- 3% of LV EDV in both sexes (p = 0.9). TPM/EDV
      decreased with age (p < 0.02) but was not associated with body mass index. TPM
      mass as a fraction of LV mass was inversely correlated with age (p < 0.0001),
      body mass index (p < 0.018), and systolic blood pressure (p < 0.0001). Among all
      1,494 participants (699 men), LV volumes decreased 23%, LV mass increased 28%,
      and EF increased by 7.5 EF units (p < 0.0001) when TPM were considered myocardial
      mass rather than part of the LV blood pool. CONCLUSIONS: Global cardiac magnetic
      resonance LV parameters were significantly affected by whether TPM was considered
      as part of the LV blood pool or as part of LV mass. Our cross-sectional data from
      a healthy referent group of adults free of clinical cardiovascular disease
      demonstrated that TPM/EDV decreases with increasing age in both sexes but is not
      related to hypertension or obesity.

PMID- 23153914
TI  - Influence of ejection fraction on the prognostic value of sympathetic innervation
      imaging with iodine-123 MIBG in heart failure.
AB  - OBJECTIVES: The aim of this study was to determine whether left ventricular
      ejection fraction (LVEF) influences the relationship between abnormal myocardial
      sympathetic innervation imaging by iodine 123 meta-iodobenzylguanidine ((123)I
      mIBG) and outcomes in patients with heart failure (HF). BACKGROUND: In systolic
      HF, both abnormal (123)I-mIBG imaging and reduced LVEF are associated with higher
      risk of cardiovascular events. Whether (123)I-mIBG imaging has the same
      predictive value across the LVEF spectrum is unclear. METHODS: Among 985 patients
      in the ADMIRE-HF (AdreView Myocardial Imaging for Risk Evaluation in Heart
      Failure) trial with New York Heart Association functional class II or III HF and
      site-reported LVEF <=35%, the core laboratory-determined LVEFs were available for
      901 subjects, ranging from 20% to 58% (mean LVEF 34 +/- 7%), and was >35% in 386
      subjects. RESULTS: The mean age of the study population was 62 +/- 12 years, 80%
      were male, and the majority had New York Heart Association functional class II
      symptoms and HF of nonischemic etiology. At all levels of LVEF, the (123)I-mIBG
      heart-to-mediastinum ratio of <1.6 was associated with a higher risk of death or
      potentially lethal arrhythmic event and of the composite of cardiovascular death,
      arrhythmic event, and HF progression. Comparing subjects with LVEF <=35% and
      >35%, there was no evidence of effect modification of LVEF on the risk associated
      with low heart-to-mediastinum ratio for death or arrhythmic event (adjusted
      hazard ratio: 2.39 [95% confidence interval (CI): 1.03 to 5.55] vs. 5.28 [95% CI:
      1.21 to 23.02]; interaction p = 0.48) and for the composite (adjusted hazard
      ratio: 1.80 [95% CI: 1.01 to 3.23] vs. 2.41 [95% CI: 1.11 to 5.23]; interaction;
      p = 0.86). For death or arrhythmic event, the heart-to-mediastinum ratio appeared
      to improve the risk discrimination beyond clinical and biomarker data among both
      LVEF groups, with improvement in the model C-statistic (0.67 vs. 0.69, p = 0.03)
      and integrated discrimination improvement (p = 0.0008). CONCLUSIONS: (123)I-mIBG
      imaging has prognostic value across a spectrum of LVEFs. Further studies may be
      warranted to prospectively test the prognostic value of (123)I-mIBG imaging in
      patients with HF and an LVEF >35%.

PMID- 23153913
TI  - Selective factor XIIa inhibition attenuates silent brain ischemia: application of
      molecular imaging targeting coagulation pathway.
AB  - OBJECTIVES: The purpose of this study was use molecular imaging targeting
      coagulation pathway and inflammation to better understand the pathophysiology of
      silent brain ischemia (SBI) and monitor the effects of factor XIIa inhibition.
      BACKGROUND: SBI can be observed in patients who undergo invasive vascular
      procedures. Unlike acute stroke, the diffuse nature of SBI and its less tangible
      clinical symptoms make this disease difficult to diagnose and treat. METHODS: We
      induced SBI in mice by intra-arterial injection of fluorescently labeled
      microbeads or fractionated clot into the carotid artery. After SBI induction,
      diffusion-weighted magnetic resonance imaging was performed to confirm the
      presence of microinfarcts in asymptomatic mice. Molecular imaging targeting the
      downstream factor XIII activity (single-photon emission computed
      tomography/computed tomography) at 3 h and myeloperoxidase activity (magnetic
      resonance imaging) on day 3 after SBI induction were performed, without and with
      the intravenous administration of a recombinant selective factor XIIa inhibitor
      derived from the hematophagous insect Triatoma infestans (rHA-Infestin-4).
      Statistical comparisons between 2 groups were evaluated by the Student t test or
      Mann-Whitney U test. RESULTS: In SBI-induced mice, we found abnormal activation
      of the coagulation cascade (factor XIII activity) and increased inflammation
      (myeloperoxidase activity) close to where emboli lodge in the brain. rHA-Infestin
      4 administration significantly reduced ischemic damage (53% to 85% reduction of
      infarct volume, p < 0.05) and pathological coagulation (35% to 39% reduction of
      factor XIII activity, p < 0.05) without increasing hemorrhagic frequency.
      Myeloperoxidase activity, when normalized to the infarct volume, did not
      significantly change with rHA-Infestin-4 treatment, suggesting that this
      treatment does not further decrease inflammation other than that resulting from
      the reduction in infarct volume. CONCLUSIONS: Focal intracerebral clotting and
      inflammatory activity are part of the pathophysiology underlying SBI. Inhibiting
      factor XIIa with rHA-Infestin-4 may present a safe and effective treatment to
      decrease the morbidity of SBI.

PMID- 23153915
TI  - Quantitative and qualitative changes in DES-related neointimal tissue based on
      serial OCT.
AB  - OBJECTIVES: The study evaluated serial quantitative and qualitative changes in
      vascular responses to drug-eluting stents (DES) using optical coherence
      tomography (OCT). BACKGROUND: Serial changes in stent strut coverage and
      neointima characteristics in DES-treated lesions have not been sufficiently
      investigated using OCT. METHODS: Serial OCT was performed in 72 patients with 76
      DES-treated lesions at 9 months and 2 years after DES implantation (sirolimus
      eluting stent, n = 23; paclitaxel-eluting stent, n = 20; zotarolimus-eluting
      stent, n = 25; everolimus-eluting stent, n = 8). Serial changes in quantitative
      parameters (neointimal thickness, stent strut coverage, and apposition at each
      strut) and qualitative characteristics of the neointima were evaluated. RESULTS:
      Mean neointimal thickness significantly increased from 164 MUm to 214 MUm between
      9 months and 2 years (p < 0.001), and the percentage of uncovered stent struts
      significantly decreased (from 4.4% to 2.3%, p < 0.001). Completely covered
      lesions were more frequently observed at 2 years (44.7% vs. 59.2%, p = 0.07).
      However, the percentage of malapposed struts (0.6% vs. 0.9%, p = 0.24) and
      incidence of intracoronary thrombi (10.5% vs. 9.2%, p > 0.99) were similar. On
      qualitative evaluation of neointimal morphology, lipid-laden neointima (27.6% vs.
      14.5%, p = 0.009) and thin-cap neoatheroma (13.2% vs. 3.9%, p = 0.07) were more
      frequently detected at 2-year follow-up compared with 9 months. In matched cross
      sectional evaluation, the change of neointimal morphology from homogeneous to
      heterogeneous or lipid-laden pattern was observed in 23 (30.3%) of 76 lesions.
      There was a significant increase in percent neointimal hyperplasia cross
      sectional area in those lesions. CONCLUSIONS: This OCT study suggested that
      neointimal coverage improved from 9 months to 2 years without significant changes
      in the incidence of malapposed struts and intracoronary thrombus. Additionally,
      in-stent neoatherosclerosis including transformation to lipid-laden neointima
      might progress during extended follow-up periods after DES implantation.

PMID- 23153916
TI  - OCT-verified peri-strut low-intensity areas and the extent of neointimal
      formation after 3 years following stent implantation.

PMID- 23153917
TI  - Quantitative assessment of mitral regurgitation: how best to do it.
AB  - Decisions regarding surgery for mitral regurgitation (MR) are predicated on the
      accurate quantification of MR severity. Quantitative parameters, including vena
      contracta width, regurgitant volume and fraction, and effective regurgitant
      orifice area have prognostic significance and are recommended to be obtained from
      patients with more than mild MR. New tools for MR quantification have been
      provided by 3-dimensional echocardiography, cardiac magnetic resonance, and
      cardiac computed tomography, but limited guidance on appropriate image
      acquisition and post-processing techniques has hindered their clinical
      application and reproducibility. This review describes optimal image acquisition
      and post-processing methods for quantification of MR.

PMID- 23153918
TI  - Enface reconstruction of VSD on RV septal surface using real-time 3D
      echocardiography.

PMID- 23153919
TI  - Delayed plaque enhancement by CT angiography.

PMID- 23153920
TI  - Pre-dismissal surveillance echocardiography second day after TAVR.

PMID- 23153921
TI  - Effective dose of PET/CT in informed consent forms.

PMID- 23153923
TI  - Intraplaque hemorrhage, RBC-derived cholesterol, and plaque progression: time to
      move from conjecture to evidence?

PMID- 23153924
TI  - On tests, times, and the test of time...

PMID- 23153925
TI  - Immunomodulatory drugs: new options for the treatment of myelodysplastic
      syndromes.
AB  - BACKGROUND: Myelodysplastic syndromes (MDS) are common adult hematologic
      disorders characterized by ineffective hematopoiesis with progressive cytopenia
      and a risk of evolving into currently incurable acute myeloid leukemia. Until
      recently, the only treatment was bone marrow transplantation, but, over the past
      few years, a new therapeutic approach based on immunomodulatory drugs (IMiD) has
      been developed. IMiDs belong to a therapeutic class whose progenitor is
      thalidomide, a synthetic derivative of glutamate that was initially used because
      of its sedative and antiemetic properties but was then withdrawn because of its
      teratogenic effects. IMiDs represent a major advance in the treatment of multiple
      myeloma at different disease stages, 5q minus syndrome, acute myeloid leukemia
      with the 5q deletion, mantle cell lymphoma, relapsing or unresponsive high-grade
      lymphoma, and relapsing indolent lymphoma. METHODS: Medical databases and
      conference proceedings were searched to identify articles and clinical trials
      that have investigated or are investigating the use of IMiDs on MDS. RESULTS AND
      DISCUSSION: An important part of their in vivo efficacy is attributed to their
      immunomodulatory properties because they potentiate the immune response by
      restoring dendritic cell function and inhibiting T-cell regulatory activity,
      which leads to the activation of T lymphocytes and natural killer T cells by
      increasing the production of interleukin-2 and interferon gamma. IMiDs are
      characterized by antitumoral and antiangiogenic activities, and they also induce
      the apoptosis of neoplastic cells. Thalidomide and its derivative lenalidomide
      have been proposed for the treatment of MDS because of their action on the immune
      mechanisms that appear to play an important role in the pathophysiology of this
      syndrome. CONCLUSIONS: This article examines the pharmacology and molecular
      action of IMiDs and the evidence of their efficacy in treating patients with MDS
      in different risk classes.

PMID- 23153926
TI  - Cost-effectiveness of vascular access for haemodialysis: arteriovenous fistulas
      versus arteriovenous grafts.
AB  - BACKGROUND: The use of an arteriovenous fistula (AVF) for haemodialysis treatment
      may be associated with a high early failure rate, but usually good long-term
      patency, while using an arteriovenous graft (AVG) yields a lower early failure
      rate with worse long-term patency. The aim of this study was to calculate and
      compare the costs and outcome of AVF and AVG surgery in terms of early and long
      term patencies. METHODS: A decision tree and a Markov model were constructed to
      calculate costs and performance of AVFs and AVGs. The model was populated with a
      retrospective cohort of HD patients receiving their first VA. The outcomes were
      determined probabilistically with a 5-year follow-up. RESULTS: AVFs were usable
      for a mean (95% CI) of 28.5 months (24.6-32.5 months), while AVGs showed a
      patency of 25.5 months (20.0-31.2 months). The use of AVFs was the dominant type
      of VA and ? 631 could be saved per patient/per month patency compared to AVG use.
      Regardless of the willingness to pay, the use of AVFs yielded a higher
      probability of being cost-effective compared to AVGs. CONCLUSIONS: AVFs are more
      cost-effective than AVGs. Nonetheless, early failure rates significantly
      influence AVF performance and initiatives to reduce early failure can improve its
      cost-effectiveness.

PMID- 23153927
TI  - Copper ion-stimulated McoA-laccase production and enzyme characterization in
      Proteus hauseri ZMd44.
AB  - The novel bioelectricity-generating bacterium of Proteus hauseri ZMd44 has been
      first identified to produce McoA-laccase (EC 1.10.3.2) induced by copper
      sulphate. The optimal concentration of copper is 3 mM as supplementation at the
      beginning of culture or early exponential growth phase, during which laccase is
      predominantly synthesized. Moreover, the whole cellular and intracellular
      activities of laccase increase in the degrees of inducible copper concentrations.
      A possible mechanism for this phenomenon is that copper ions enhance the laccase
      genetic transcription level during the laccase synthesis thus granting this
      strain in copper tolerance. McoA-laccase belongs to typical type 1 (T1) Cu site
      laccase by electron paramagnetic resonance (EPR) analysis of intracellular
      enzyme. From our results, the optimal temperature and pH are 60 degrees C and pH
      2.2, respectively. The kinetic profiles show that this enzyme is stable under 50
      degrees C and in the slightly acidic environment, making it a potentially useful
      enzyme in dye decolorization, paper-pulp bleaching and bioremediation industries.

PMID- 23153928
TI  - Downregulation of extracellular signal-regulated kinase 1/2 activity by
      calmodulin KII modulates p21Cip1 levels and survival of immortalized lymphocytes
      from Alzheimer's disease patients.
AB  - Previously, we reported a Ca(2+)/calmodulin (CaM)-dependent impairment of
      apoptosis induced by serum deprivation in Alzheimer's disease (AD) lymphoblasts.
      These cell lines showed downregulation of extracellular signal-regulated kinase
      (ERK)1/2 activity and elevated content of p21 compared with control cells. The
      aim of this study was to delineate the molecular mechanism underlying the
      distinct regulation of p21 content in AD cells. Quantitative reverse
      transcription polymerase chain reaction analysis demonstrated increased p21
      messenger RNA (mRNA) levels in AD cells. The ERK1/2 inhibitor, PD98059, prevented
      death of control cells and enhanced p21 mRNA and protein levels. The CaM
      antagonist, calmidazolium, and the CaMKII inhibitor, KN-62, normalized the
      survival pattern of AD lymphoblasts by augmenting ERK1/2 activation and reducing
      p21 mRNA and protein levels. Upregulation of p21 transcription in AD cells
      appears to be the consequence of increased activity of forkhead box O3a (FOXO3a)
      as the result of diminished ERK1/2-mediated phosphorylation of this transcription
      factor, which in turn facilitates its nuclear accumulation. Murine double minute
      2 (MDM2) protein levels were decreased in AD cells relative to control
      lymphoblasts, suggesting an impairment of FOXO3a degradation.

PMID- 23153929
TI  - Supportive evidence for 11 loci from genome-wide association studies in
      Parkinson's disease.
AB  - Genome-wide association studies have identified a number of susceptibility loci
      in sporadic Parkinson's disease (PD). Recent larger studies and meta-analyses
      have greatly expanded the list of proposed association signals. We performed a
      case-control replication study in a Scandinavian population, analyzing samples
      from 1345 unrelated PD patients and 1225 control subjects collected by
      collaborating centers in Norway and Sweden. Single-nucleotide polymorphisms
      representing 18 loci previously reported at genome-wide significance levels were
      genotyped, as well as 4 near-significant, suggestive, loci. We replicated 11
      association signals at p < 0.05 (SNCA, STK39, MAPT, GPNMB, CCDC62/HIP1R, SYT11,
      GAK, STX1B, MCCC1/LAMP3, ACMSD, and FGF20). The more recently nominated
      susceptibility loci were well represented among our positive findings, including
      3 which have not previously been validated in independent studies. Conversely,
      some of the more well-established loci failed to replicate. While future meta
      analyses should corroborate disease associations further on the level of common
      markers, efforts to pinpoint functional variants and understand the biological
      implications of each risk locus in PD are also warranted.

PMID- 23153930
TI  - New political party will target prime minister and five others implicated in NHS
      changes.

PMID- 23153931
TI  - The competitive NMDA receptor antagonist CPP disrupts cocaine-induced conditioned
      place preference, but spares behavioral sensitization.
AB  - Recently, the notion that memory and addiction share similar neural substrates
      has become widely accepted. N-methyl-d-aspartate receptors (NMDAR) are the
      cornerstones of synaptic models of memory. The present study examined the effect
      of the competitive NMDAR antagonist CPP on the induction of behavioral
      sensitization and conditioned place preference to cocaine. Conditioned place
      preference is an associative memory model of drug seeking, while sensitization is
      a non-associative model of the transition from casual to compulsive use. There
      were three principal findings: (1) co-administration of CPP and cocaine altered
      the acute response to cocaine, suggesting a direct interaction between the two
      drugs; (2) NMDAR antagonism had no effect on behavioral sensitization; and (3)
      NMDAR antagonism abolished conditioned place preference. A review of prior
      evidence supporting a role for NMDARs in sensitization suggests that NMDAR
      antagonists directly interfere with cocaine's psychostimulant effects, and this
      interaction could be misinterpreted as a disruption of sensitization. Finally, we
      suggest that addiction recruits multiple kinds of plasticity, with sensitization
      recruiting NMDAR-independent mechanisms.

PMID- 23153932
TI  - Diagnosing autism in neurobiological research studies.
AB  - Autism spectrum disorder (ASD) is by definition a complex and heterogeneous
      disorder. Variation in factors such as developmental level, language ability and
      IQ further complicate the presentation of symptoms. Clinical research and basic
      science must continue to inform each other's questions to help address the
      heterogeneity inherent to the disorder. This review uses a clinical perspective
      to outline the common tools and best practices for diagnosing and characterizing
      ASD in a research setting. We discuss considerations for classifying research
      populations, including language ability and IQ and examine the advantages and
      disadvantages of different psychometric measurements. Ultimately, the
      contribution of multiple sources of data representing different perspectives is
      crucial for interpreting and understanding the ASD phenotype.

PMID- 23153933
TI  - An antiprogestin, CDB4124, blocks progesterone's attenuation of the negative
      effects of a mild stress on sexual behavior.
AB  - These experiments were designed to test the hypothesis that a progesterone
      receptor antagonist would block progesterone's ability to reduce the negative
      effects of a 5 min restraint on female rat sexual behavior. Ovariectomized
      Fischer rats were injected with 10 MUg estradiol benzoate. Two days later, rats
      were injected subcutaneously (sc) with the progesterone receptor antagonist,
      CDB4124 (17alpha-acetoxy-21-methoxy-11beta-[4-N,N-dimethyaminopheny]-19-norpregna
      4,9-dione-3,20-dione) (60 mg/kg), or vehicle (20% DMSO+propylene glycol). One
      hour later, rats were injected sc with 500 MUg progesterone or vehicle (sesame
      seed oil). Rats were assigned to one of three different treatment conditions: (1)
      (ECV) estradiol benzoate, CDB4124, sesame seed oil vehicle, (2) (ECP) estradiol
      benzoate, CDB4124, progesterone, and (3) (EVP) estradiol benzoate, DMSO/propylene
      glycol vehicle, progesterone. That afternoon sexual behavior was examined before
      and after a 5 min restraint experience. Before restraint, lordosis behavior was
      comparable across treatment conditions but only progesterone-treated rats
      exhibited proceptive behavior. CDB4124 did not block progesterone's induction of
      proceptivity. However, after restraint, CDB4124 attenuated the positive effects
      of progesterone on all sexual behaviors examined. The restraint experience
      inhibited sexual behavior in rats treated with estradiol benzoate and CDB4124 and
      in rats treated with estradiol benzoate, CDB4124, and progesterone but not in
      rats given estradiol benzoate and progesterone without CDB4124. These findings
      are consistent with the hypothesis that progesterone receptors mediate
      progesterone's ability to reduce the negative sexual behavioral effects of a mild
      stressor.

PMID- 23153935
TI  - Robotic partial nephrectomy for solitary kidney: a multi-institutional analysis.
AB  - OBJECTIVE: To evaluate the outcomes of robotic partial nephrectomy (RPN) for
      solitary kidney in a large multicenter series. MATERIALS AND METHODS: Medical
      records of 886 consecutive patients who underwent RPN at 5 academic institutions
      from May 2007 to May 2012 were retrospectively analyzed. Data were prospectively
      collected in an Investigational Review Board-approved protocol. Experienced
      robotic surgeons performed all operations. Patient demographics, functional,
      perioperative, and early oncologic outcomes were analyzed. RESULTS: A total of 26
      patients with a solitary kidney were identified and included in the analysis; of
      these, 16 (62%) had solitary kidneys secondary to a previous malignancy.
      Perioperative outcomes included a median warm ischemia time of 17 minutes
      (interquartile range, 12, 28 minutes). Only 2 intraoperative complications
      occurred. One was a renal vein injury and one an aortic vessel tear, and both
      patients required intraoperative blood transfusions. No conversions to
      laparoscopy or open surgery occurred. There were 3 postoperative complications
      (11.5%). Median follow-up was 6 months (interquartile range, 5, 9.7 months).
      Postoperative renal function did not change significantly as measure by estimated
      glomerular filtration rate (-15.8%; P=.13). None of the patients required
      dialysis. Positive margins occurred in 1 patient, with 73% of patients having a
      renal cell carcinoma. CONCLUSION: We report a multi-institutional series of RPN
      in patients with solitary kidney presenting with small renal masses. Our findings
      suggest that RPN represents a feasible treatment option in this specific
      population by offering reliable preservation of renal function, low surgical
      morbidity, and early oncologic safety in the hands of experienced robotic
      surgeons.

PMID- 23153934
TI  - Probability of downsizing primary tumors of renal cell carcinoma by targeted
      therapies is related to size at presentation.
AB  - OBJECTIVE: To evaluate the probability of downsizing primary renal tumors by
      targeted therapy in correlation to size. METHODS: A literature search was
      conducted and our own data were pooled with data of retrospective series and
      prospective trials in which patients were treated with tyrosine kinase inhibitors
      (TKIs) and in which tumor sizes before and after treatment were reported.
      Included were 89 primary clear cell renal tumors, including 34 from our
      institutes. The longest diameter of the primary tumors before and after treatment
      was obtained. Primary tumor size at presentation was divided in 4 categories: <5
      cm (n=10), 5 to 7 cm (n=21), 7 to 10 cm (n=31), and >10 cm (n=27). Pearson
      correlation and t test were used for statistical analysis. RESULTS: The TKI was
      sorafenib in 21 tumors and sunitinib in the remaining 68. Smaller tumor size was
      related to more effective downsizing (P=0.01). Median downsizing was 32% (-46% to
      11%) in the first group (<5 cm) and 11% (-55% to 16%) in the second group (5-7
      cm); however, 8 of 21 (38%) in this group reduced to a range of 2.3 to 4.7 cm in
      which ablative techniques are feasible and nephron-sparing surgery may benefit
      from the reduced size. Median downsizing was 18% (-39% to 2%) in tumors of 7 to
      10 cm and 10% (-31% to 0%) in those>10 cm. CONCLUSION: The smaller the primary
      tumor, the greater the likelihood and the more effective the downsizing. A
      potential benefit of neoadjuvant treatment to downsize the primary tumor for
      ablative techniques or nephron-sparing surgery may exist, particularly in tumors
      sized 5 to 7 cm.

PMID- 23153936
TI  - Occurrence of dysplasia and human papilloma virus typing in penile condylomas.
AB  - OBJECTIVE: To determine the incidence of dysplasia as a preneoplastic change and
      high-risk human papilloma virus (HPV) infection in penile condylomas, which are
      common HPV-related lesions and considered a risk factor for penile cancer.
      METHODS: Histologic analysis was done of 58 consecutive penile condylomas with
      tissue diagnosis. An immunohistochemical panel that included stains for p53, Ki
      67, and p16INK4a was also used. HPV typing was successfully performed in 43
      lesions. Genotyping was accomplished through polymerase chain reaction and flow
      through hybridization with an HPV GenoArray Diagnostic Test kit. RESULTS:
      Dysplasia was observed in 13 of the 58 condylomas (22%). High-risk HPV DNA was
      detected in 5 of 10 dysplastic lesions (50%) for which tissue blocks were
      available for study. High-risk HPV was not detected in the nondysplastic lesions
      (P<.001). Ki-67>=20% above the basal layer of epithelium and p53-positive
      immunostaining occurred more frequently in dysplastic lesions than in
      nondysplastic lesions; however, the difference was not statistically
      significance. Staining for p16INK4a was not helpful. CONCLUSION: Anogenital
      condylomas in men are usually treated using destructive methods or with
      medication. We suggest that at least a part of the lesion must be removed and
      sent for histopathologic examination. If the histologic result shows significant
      dysplastic alteration, the lesion should be further investigated to determine the
      subtype of infective virus, because 50% of such lesions are associated with high
      risk HPV. When oncogenic pathogens are found, careful patient follow-up for
      recurrences and counseling for the patient and his sexual partner(s) may be
      warranted.

PMID- 23153937
TI  - Solid testicular mass in a 63-year-old man.

PMID- 23153938
TI  - Effect of diabetes on the ion pumps of the bladder.
AB  - OBJECTIVE: To establish whether the activities of Na+/K+-adenosine triphosphatase
      (ATPase) and Ca2+-ATPases ion pumps in bladder smooth muscle are altered as a
      consequence of diabetes and, if so, how this might contribute to bladder
      cystopathy. Urinary bladder dysfunction is a common occurrence in patients with
      diabetes. Pressure generation requires calcium and cytosolic ATP. Activities of
      these pumps are responsible for calcium homeostasis. METHODS: Rat urinary
      detrusor muscle strips were suspended in organ baths containing Krebs solution
      for isometric tension recording. Tissue responses to the Na+/K+-ATPase pump
      inhibitor, ouabain, the plasma membrane Ca2+ ATPase inhibitor, vanadate, and the
      sarcoplasmic reticulum Ca2+ ATPase inhibitor, cyclopiazonic acid (CPA), were
      examined from normal and streptozocin-induced diabetic rats for 2, 4, and 12
      weeks. RESULTS: Ouabain, vanadate, and CPA caused concentration-dependent
      contractions of bladder strips from diabetic and normal rats. The degree of
      contraction of diabetic bladder muscle was lower than that of controls. This
      reduction was a function of duration of diabetes. For ouabain, the reduction
      peaked at 2 weeks, with partial restoration to normal after diabetes induction.
      For vanadate and CPA, the reduction increased with the duration of diabetes.
      CONCLUSION: The ion pumps are important modulators of bladder smooth muscle tone,
      and in a rat model of streptozotocin-induced diabetes, the activity of these
      pumps is impaired. Although this is only a single model of diabetes, these
      findings suggest that a defect in these pumps may be an important component of
      the development of diabetic bladder cystopathy.

PMID- 23153939
TI  - Inducing cell proliferation inhibition, apoptosis, and motility reduction by
      silencing long noncoding ribonucleic acid metastasis-associated lung
      adenocarcinoma transcript 1 in urothelial carcinoma of the bladder.
AB  - OBJECTIVE: To study the expression patterns of long noncoding ribonucleic acid
      (RNA) metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) and the
      cell proliferation inhibition, apoptosis, and motility changes induced by
      silencing MALAT1 in urothelial carcinoma of the bladder. MATERIALS AND METHODS:
      The expression levels of MALAT1 were determined using real-time quantitative
      polymerase chain reaction in cancerous tissues and paired normal tissues in a
      total of 36 patients with urothelial carcinoma of the bladder. Expression
      differences were analyzed according to the grade and stage. Bladder urothelial
      carcinoma T24 and 5637 cells were transfected with MALAT1 small interfering RNA
      or negative control small interfering RNA. The cell proliferation changes of the
      transfected bladder urothelial carcinoma cells were determined using the MTT
      assay. Apoptosis caused by silencing MALAT1 was evaluated using the flow
      cytometry assay and enzyme-linked immunosorbent assay. The motility changes
      induced by silencing MALAT1 were measured using the wound healing assay. RESULTS:
      MALAT1 was upregulated in bladder urothelial carcinoma compared with matched
      normal urothelium (P=.008). The MALAT1 expression levels were greater in high
      grade carcinomas than in low-grade carcinoma (P=.001). The MALAT1 expression
      levels were greater in invasive carcinoma than in noninvasive carcinoma (P=.018).
      Cell proliferation inhibition, increased apoptosis, and decreased motility were
      observed in MALAT1 small interfering RNA-transfected bladder urothelial carcinoma
      T24 and 5637 cells. CONCLUSION: MALAT1 plays an oncogenic role in urothelial
      carcinoma of the bladder. Silencing MALAT1 is a potential novel therapeutic
      approach for this cancer.

PMID- 23153940
TI  - Simvastatin suppresses cyclophosphamide-induced changes in urodynamics and
      bladder inflammation.
AB  - OBJECTIVE: To assess the ability of daily oral simvastatin administration to
      reduce the negative urodynamic changes associated with cyclophosphamide (CP)
      induced cystitis and to prevent bladder inflammation. Patients undergoing CP
      chemotherapy frequently develop cystitis, leading to urinary dysfunction and
      hemorrhage. Recent studies have suggested statins possess anti-inflammatory
      properties and might be uroprotective. MATERIALS AND METHODS: Urodynamic
      properties were analyzed in 4 groups of female Sprague-Dawley rats: group 1,
      vehicle (300 MUL, 0.5% methylcellulose, orally for 7 days); group 2, simvastatin
      (1 mg/rat/d); group 3, vehicle plus CP (intraperitoneally 80 mg/kg, 24 h before
      cystometry); and group 4, simvastatin plus CP. The inflammation in the groups was
      assessed using Evans blue extravasation. RESULTS: CP stimulated significant
      increases in the number of nonvoiding contractions (0.83+/-0.26 vs 4.97+/-1.90;
      P=.03) and decreases in the peak voiding pressure (53.46+/-5.08 vs 33.34+/-4.37
      cm H2O; P=.01). Simvastatin returned these parameters to the control levels of
      1.62+/-0.73 (P=.70) and 45.98+/-7.78 cm H2O (P=.38). CP at this level caused a
      slight, but significant, increase in the voided volume (0.82+/-0.13 vs 1.16+/
      0.14 mL; P=.04), which returned to control levels (0.74+/-0.12 mL; P=.65) with
      simvastatin. Other urodynamic parameters, such as the threshold pressure, were
      not affected by simvastatin or CP, or the combination of the 2. CP-induced
      inflammation in the bladder (Evans blue extravasation) was suppressed by
      simvastatin. CONCLUSION: Simvastatin was effective at ameliorating the negative
      urodynamic changes and inflammation in the bladder after CP administration and is
      a potential therapy for preventing side effects in patients undergoing this
      chemotherapy.

PMID- 23153942
TI  - Better irrigation delivers better vision: an exploratory study of a novel
      continuous irrigation sheath for a flexible cystoscope.
AB  - OBJECTIVE: To evaluate the effectiveness of a novel continuous irrigation sheath
      (NCIS) for improving the vision of a flexible cystoscope under gross hematuria
      and to investigate whether this NCIS increases patient discomfort. METHODS: A
      model was designed and a trial was conducted to quantitatively evaluate the
      effectiveness of the NCIS in vitro. The trial was divided into a static and a
      dynamic trial. The main difference between these two parts of the trial was the
      presence of continuous hemorrhage. There were 3 levels for the irrigation
      condition: no irrigation (group 1), continuous irrigation without an outflow of
      water (group 2), and continuous irrigation with an outflow of water (group 3).
      Flexible cystoscopy was conducted under different conditions and repeated, and
      the main outcome measures, including field of flexible cystoscope's vision (FFCV)
      and definition of the pictures taken by the flexible cystoscope (DFC), were
      measured at 30, 60, 90 and 120 seconds. To investigate whether the NCIS increased
      patient discomfort, 36 patients were randomized into 2 groups to receive flexible
      cystoscopy with or without the NCIS. RESULTS: Compared with groups 1 and 2, the
      FFCV and DFC values were significantly increased in group 3; however, the FFCV
      was not significantly increased compared with group 2 in the static model. The
      pain scores between patients who received flexible cystoscopy with or without the
      NCIS did not differ significantly. CONCLUSION: The NCIS effectively improved the
      vision of a flexible cystoscope without increasing patient discomfort.

PMID- 23153945
TI  - Editorial comment.

PMID- 23153947
TI  - Editorial comment.

PMID- 23153948
TI  - Editorial comment.

PMID- 23153949
TI  - Hypertension in pediatric patients with renal scarring in association with
      vesicoureteral reflux.
AB  - OBJECTIVE: To examine the reflux nephropathy rate and severity as well as the
      hypertension rate in pediatric patients with vesicoureteral reflux (VUR).
      METHODS: The study included 240 patients with VUR. Renal scarring (RS) was
      demonstrated by renal parenchymal examination using technetium-99m-labeled
      dimercaptosuccinic acid (99mTc-DMSA) scintigraphy. Office measurements of
      arterial blood pressure and ambulatory blood pressure monitoring (ABPM) of VUR
      patients were done during the follow-up period. RESULTS: Follow-up was a mean
      duration of 24 months. Rates of RS and hypertension increased parallel to
      increases in the degree of VUR. A gradual elevation in hypertension rates was
      evident during the follow-up period. All patients with hypertension had RS.
      Severe RS in 56 patients was associated with increasing blood pressure readings
      by 24-hour ABPM or office measurements in 19 patients (33.9%). ABPM measurements
      enabled us to detect additional patients compared with office measurements alone.
      CONCLUSION: Hypertension is a serious complication in children with reflux
      nephropathy and is associated with the severity of RS and VUR grade. ABPM seems
      to be superior over office measurements of blood pressure in identifying patients
      with hypertension.

PMID- 23153950
TI  - Incidence, risk factors, and complications of postoperative delirium in elderly
      patients undergoing radical cystectomy.
AB  - OBJECTIVE: To identify the risk factors for, and complications associated with,
      the development of delirium after radical cystectomy. MATERIALS AND METHODS: From
      July 2008 to December 2009, 59 patients, aged >=65 years and undergoing radical
      cystectomy, were prospectively enrolled. The baseline cognitive status was
      assessed using the Mini-Mental Status Examination. Postoperative delirium was
      assessed using the Confusion Assessment Method. RESULTS: A total of 49 patients
      completed the surgery and all assessments. The incidence of postoperative
      delirium was 29%, with duration of 1-5 days. On univariate analysis, older age
      and preoperative Mini-Mental Status Examination score were associated with
      postoperative delirium. On multivariate analysis, only age was associated with
      postoperative delirium (odds ratio 1.52, 95% confidence interval 1.04-2.22,
      P=.03). The 2 groups did not differ in pathologic stage, length of surgery,
      intraoperative and postoperative narcotic usage, body mass index, age-adjusted
      Charlson comorbidity index, activities of daily living scores, smoking history,
      preoperative hematocrit, estimated blood loss, urinary tract infection, interval
      to a regular diet, or length of hospital stay. The patients who developed
      postoperative delirium were more likely to undergo readmission (odds ratio 10.7,
      95% confidence interval 2.2-51.8, P=.01) and reoperation (odds ratio 9.2, 95%
      confidence interval 1.5-55.3, P=.03) but did not differ in the 90-day and 1-year
      mortality rates or incidence of postoperative complications. CONCLUSION: In
      patients aged>=65 years, a lower preoperative Mini-Mental Status Examination
      score and older age were significantly associated with the development of
      postcystectomy delirium, as measured using the Confusion Assessment Method. The
      patients who developed delirium were more likely to undergo readmission and
      reoperation. Larger studies with multiple surgeons are needed to validate these
      findings.

PMID- 23153951
TI  - Contemporary urethral stricture characteristics in the developed world.
AB  - OBJECTIVE: To assess the current etiology, features, and natural history of
      urethral stricture disease in the developed world. MATERIALS AND METHODS: We
      analyzed the data from 1439 male patients with urethral stricture, who had
      undergone surgical treatment in our referral urethral center from 2000 to 2010.
      The preoperative evaluation included a detailed clinical history of stricture,
      uroflowmetry, retrograde and voiding cystourethrography, and urethroscopy.
      Statistical analysis was done for the stricture site, length, and etiology,
      patient age, and previous treatments. RESULTS: Strictures were posterior in 112
      (7.8%) and anterior in 1327 (92.2%). In the anterior group, 439 were penile
      (30.5%), 675 bulbar (46.9%), 71 penile plus bulbar (9.9%), and 142 panurethral
      (4.9%). The main causes were iatrogenic in 556 (38.6%), unknown in 515 (35.8%),
      lichen sclerosus in 193 (13.4%), and trauma in 156 (10.8%). The main iatrogenic
      strictures were from catheterization in 234 (16.3%), hypospadias repair in 176
      (12.2%), and transurethral surgery in 131 (9.1%). The stricture distribution
      increased until about 45 years and then decreased. Strictures were uncommon in
      those<20 and >70 years old. The mean length was 4.15 cm; longer strictures were
      found in those with lichen sclerosus (7.45 cm) or after hypospadias repair (4.42
      cm) and catheterization (4.40 cm). The mean length was also greater in the
      pretreated (4.34 cm) than in the untreated (3.64 cm) strictures. CONCLUSION:
      Urethral stricture in developed countries mainly involves the anterior urethra,
      in particular the bulbar tract. The most common cause was iatrogenic. Hypospadias
      repair and lichen sclerosus represent emerging important causes. Finally,
      urethral stricture is not a disease of the elderly but involves all ages.

PMID- 23153952
TI  - Knowledge and attitude of European urology residents about ionizing radiation.
AB  - OBJECTIVE: To evaluate the attitude and knowledge of urology residents concerning
      ionizing radiation, we undertook a survey of European urology residents. METHODS:
      The questionnaire was sent to 1184 urology residents within the database of the
      European Society of Residents in Urology (ESRU) by e-mail between November 2011
      and January 2012. The questionnaire was composed of demographic questions and
      questions about the frequency of radiation exposure and use of radiation safety
      measures during fluoroscopy-guided endourologic procedures. In addition, there
      were questions about education programs and respondents' knowledge about
      diagnostic imaging modalities. RESULTS: A total of 124 questionnaires were
      returned from urology residents in 20 different European countries. All of the
      respondents reported that they were routinely exposed to ionizing radiation, and
      69 (72.5%) were exposed more than 3 times per week. Despite the common but not
      sufficient use of lead aprons (75%), use of other radiation protection measures
      was very low. Although 55% of the respondents had attended an education program
      in Europe about radiation safety, attendance was highest in Poland (82.6%). The
      level of knowledge about ionizing radiation was low among urology residents, and
      approximately half of responders had no idea that commonly used imaging
      modalities have a fatal cancer risk. CONCLUSION: The results of this study showed
      the lack of knowledge and awareness about the importance of ionizing radiation
      protection among urology residents in Europe. We therefore suggest radiation
      safety courses in every step of medical life for doctors, especially for
      endourologists.

PMID- 23153953
TI  - Protective effects of reducing renal ischemia-reperfusion injury during renal
      hilar clamping: use of allopurinol as a nephroprotective agent.
AB  - OBJECTIVE: To investigate the relationship between renal ischemia injury and
      concentrations of 8-isoprostane in a rat kidney model during renal hilar clamping
      and their correlation with the administration of allopurinol before clamping.
      MATERIALS AND METHODS: Reperfusion injury occurs after the reintroduction of
      blood flow after a prolonged period of ischemia. Thought to be due to oxygen free
      radicals released by the endothelial, mitochondrial, and parenchymal cells, this
      process leads to a cascade of events whereby infiltrative leukocytes generate
      cytokines and reactive oxygen species. The present study was performed in 2
      parts. Our primary objective was to first develop a method of quantitating the
      renal damage using a prostaglandin compound formed in vivo, specifically
      isoprostane. After the development of this animal model of quantitating renal
      injury, our second objective was to apply this model and investigate
      allopurinol's nephroprotective abilities. A microdialysis probe was inserted into
      the renal parenchyma of rats to allow continuous dialysis and collection of the
      effluent for isoprostane levels. After clamping of the renal vessels to induce
      ischemia, the interstitial effluent from the probe was collected and subsequently
      analyzed for 8-isoprostane levels with and without allopurinol pretreatment.
      RESULTS: Clamping of the renal hilum in this rat model significantly increased 8
      isoprostane levels. After 60 minutes of clamp time, the largest absolute increase
      in 8-isoprostane levels resulted, representing a 3.2-fold increase from baseline.
      However, the rats that had been pretreated with allopurinol demonstrated
      significantly less isoprostane levels, to baseline levels. CONCLUSION:
      Allopurinol has demonstrated significant benefits by reducing reperfusion injury
      in rat kidneys, as demonstrated by the use of 8-isoprostane as a tool for the
      real-time measurement of ischemic injury.

PMID- 23153954
TI  - Laparoendoscopic single site (LESS) in vivo suturing using a magnetic anchoring
      and guidance system (MAGS) camera in a porcine model: impact on ergonomics and
      workload.
AB  - OBJECTIVE: To compare the ergonomics and workload of the surgeon during single
      site suturing while using the magnetic anchoring and guidance system (MAGS)
      camera vs a conventional laparoscope. METHODS: Seven urologic surgeons were
      enrolled and divided into an expert group (n=2) and a novice group (n=5)
      according to their laparoendoscopic single-site (LESS) experience. Each surgeon
      performed 2 conventional LESS and 2 MAGS camera-assisted LESS vesicostomy
      closures in a porcine model. A Likert scale (scoring 1-5) questionnaire assessing
      workload, ergonomics, technical difficulty, visualization, and needle handling,
      as well as a validated National Aeronautics and Space Administration Task Load
      Index (NASA-TLX) questionnaire were used to evaluate the tasks and workloads.
      RESULTS: MAGS LESS suturing was universally favored by expert and novice surgeons
      compared with conventional LESS in workload (3.4 vs 4.2), ergonomics (3.4 vs
      4.4), technical challenge (3.3 vs 4.3), visualization (2.4 vs 3.3), and needle
      handling (3.1 vs 3.9 respectively; P<.05 for all categories). Surgeon NASA-TLX
      assessments found MAGS LESS suturing significantly decreased the workload in
      physical demand (P=.004), temporal demand (P=.017), and effort (P=.006). External
      instrument clashing was significantly reduced in MAGS LESS suturing (P<.001). The
      total operative time of MAGS LESS suturing was comparable to that of conventional
      LESS (P=.89). CONCLUSION: MAGS camera technology significantly decreased surgeon
      workload and improved ergonomics. Nevertheless, LESS suturing and knot tying
      remains a challenging task that requires training, regardless of which camera is
      used.

PMID- 23153955
TI  - The dietary pattern of patients with schizophrenia: a systematic review.
AB  - OBJECTIVE: People with schizophrenia show a high incidence of metabolic syndrome,
      which is associated with a high mortality from cardiovascular disease. The
      aetiology of the metabolic syndrome in schizophrenia is multi-factorial and may
      involve antipsychotic treatment, high levels of stress and unhealthy lifestyle,
      such as poor diet. As a poor diet can predispose to the development of metabolic
      abnormalities, the aims of this review are to clarify: 1) the dietary patterns of
      patients with schizophrenia, 2) the association of these dietary patterns with a
      worse metabolic profile, and 3) the possible factors influencing these dietary
      patterns. METHODS: A search was conducted on Pubmed, The Cochrane Library,
      Scopus, Embase, Ovid, Psychoinfo and ISI web of Knowledge from 1950 to the 1st of
      November 2011. 783 articles were found through the investigation of such
      databases. After title, abstract or full-text reading and applying exclusion
      criteria we reviewed 31 studies on dietary patterns and their effects on
      metabolic parameters in schizophrenia. RESULTS: Patients with schizophrenia have
      a poor diet, mainly characterized by a high intake of saturated fat and a low
      consumption of fibre and fruit. Such diet is more likely to increase the risk to
      develop metabolic abnormalities. Data about possible causes of poor diet in
      schizophrenia are still few and inconsistent. CONCLUSION: Subjects with
      schizophrenia show a poor diet that partly accounts for their higher incidence of
      metabolic abnormalities. Further studies are needed to clarify the causes of poor
      diet and the role of dietary intervention to improve their physical health.

PMID- 23153956
TI  - Sex of newborns associated with place and mode of delivery: a population-based
      study in northern Vietnam.
AB  - BACKGROUND: There is increasing evidence of an elevated sex ratio at birth (SRB)
      in many Asian countries, including Vietnam, and that this prenatal gender
      inequity is related to sex-selective abortion. However, few studies have
      investigated the relation between the sex of offspring and delivery care
      utilization. OBJECTIVE: The aim of the present study was to relate sex of
      newborns to place and mode of delivery in a province in northern Vietnam.
      METHODS: A population-based surveillance system within the Neonatal Health
      Knowledge Into Practice (NeoKIP) project (ISRCTN44599712) recorded all births
      within eight districts of Quang Ninh province in northern Vietnam from July 2008
      to June 2011. RESULTS: In total, there were 22,377 live births within the study
      area. SRB was 108 boys per 100 girls. There was a large difference in SRB
      depending on place of delivery, with 94 boys per 100 girls being delivered at
      home, whereas 113 boys per 100 girls were delivered at a district-level hospital.
      Cesarean section (CS) rate was 17%, and within the CS group, the SRB was 135:100.
      CONCLUSIONS: We demonstrated an elevated SRB, especially at district hospital
      level, and that sex of offspring influenced place and mode of delivery. Although
      mothers to boys were more likely to receive more qualified delivery care, they
      were at the same time more likely to undergo unnecessary surgery. Correct
      information to women and family members about CS and stricter implementation of
      the medical indications for CS are urgently called for.

PMID- 23153957
TI  - The high mobility group box: the ultimate utility player of a cell.
AB  - High mobility group (HMG) box proteins are abundant and ubiquitous DNA binding
      proteins with a remarkable array of functions throughout the cell. The structure
      of the HMG box DNA binding domain and general mechanisms of DNA binding and
      bending have been known for more than a decade. However, new mechanisms that
      regulate HMG box protein intracellular translocation, and by which HMG box
      proteins recognize DNA with and without sequence specificity, have only recently
      been uncovered. This review focuses primarily on the Sry-like HMG box family,
      HMGB1, and mitochondrial transcription factor A. For these proteins, structural
      and biochemical studies have shown that HMG box protein modularity, interactions
      with other DNA binding proteins and cellular receptors, and post-translational
      modifications are key regulators of their diverse functions.

PMID- 23153959
TI  - Three-dimensional imaging of collagen fibril organization in rat circumferential
      lamellar bone using a dual beam electron microscope reveals ordered and
      disordered sub-lamellar structures.
AB  - Lamellar bone is a major component of most mammalian skeletons. A prominent
      component of individual lamellae are parallel arrays of mineralized type I
      collagen fibrils, organized in a plywood like motif. Here we use a dual beam
      microscope and the serial surface view (SSV) method to investigate the three
      dimensional collagen organization of circumferential lamellar bone from rat
      tibiae after demineralization and osmium staining. Fast Fourier transform
      analysis is used to quantitatively identify the mean collagen array orientations
      and local collagen fibril dispersion. Based on collagen fibril array orientations
      and variations in fibril dispersion, we identify 3 distinct sub-lamellar
      structural motifs: a plywood-like fanning sub-lamella, a unidirectional sub
      lamella and a disordered sub-lamella. We also show that the disordered sub
      lamella is less mineralized than the other sub-lamellae. The hubs and junctions
      of the canalicular network, which connect radially oriented canaliculi, are
      intimately associated with the disordered sub-lamella. We also note considerable
      variations in the proportions of these 3 sub-lamellar structural elements among
      different lamellae. This new application of Serial Surface View opens the way to
      quantitatively compare lamellar bone from different sources, and to clarify the 3
      dimensional structures of other bone types, as well as other biological
      structural materials.

PMID- 23153960
TI  - The SAPHO syndrome.
AB  - OBJECTIVE: To review the epidemiology, presentation, diagnosis, treatment,
      pathogenesis, and genetics of the syndrome known under the acronym of SAPHO for
      Synovitis, Acne, Pustulosis, Hyperostosis, and Osteitis to heighten awareness of
      this entity. METHODS: We conducted a Medline search using SAPHO syndrome, chronic
      recurrent multifocal osteitis/osteomyelitis, and related terms as keywords and
      extracted further relevant articles from the retrieved references. RESULTS: The
      SAHPO acronym identifies a syndrome encompassing a variety of osteoarticular
      disorders that are frequently accompanied by dermatoses characterized by
      neutrophilic pseudoabscesses, but can also occur in isolation. SAPHO syndrome is
      rare, although probably underrecognized because its diagnosis may be challenging
      because of the wide variability in its musculoskeletal and cutaneous
      manifestations. This is especially true when atypical sites are involved and when
      specific skin lesions are absent. There are no standardized treatment protocols
      available. Current treatments are empirical and have the objective of providing
      relief from the at times debilitating pain associated with SAPHO syndrome. They
      include nonsteroidal anti-inflammatory drugs and analgesics as first-line agents.
      Systemic corticosteroids, disease-modifying anti-rheumatic drugs, biologicals
      targeting tumor necrosis factor alpha and interleukin-1, and bisphosphonates have
      all been beneficial in some patients, but ineffective in others. This suggests
      that the pathogenesis of SAPHO syndrome is multifactorial, but this aspect
      remains poorly explored, although bacteria and immunological dysfunction are
      hypothesized to play a role. CONCLUSIONS: The early recognition, diagnosis, and
      prompt treatment of SAPHO syndrome can prevent the unnecessary use of long-term
      antibiotics or invasive procedures, while rapidly alleviating pain in a majority
      of affected patients.

PMID- 23153961
TI  - High in vitro antimicrobial activity of beta-peptoid-peptide hybrid oligomers
      against planktonic and biofilm cultures of Staphylococcus epidermidis.
AB  - An array of beta-peptoid-peptide hybrid oligomers displaying different amino
      acid/peptoid compositions and chain lengths was studied with respect to
      antimicrobial activity against Staphylococcus epidermidis both in planktonic and
      biofilm cultures, comparing the effects with those of the common antibiotic
      vancomycin. Susceptibility and time-kill assays were performed to investigate
      activity against planktonic cells, whilst confocal laser scanning microscopy was
      used to investigate the dynamics of the activity against cells within biofilms.
      All tested peptidomimetics were bactericidal against both exponentially growing
      and stationary-phase S. epidermidis cells with similar killing kinetics. At the
      minimum inhibitory concentration (MIC), all peptidomimetics inhibited biofilm
      formation, whilst peptidomimetics at concentrations above the MIC (80-160MUg/mL)
      eradicated young (6-h-old) biofilms, whilst even higher concentrations were
      needed to eradicate mature (24-h-old) biofilms completely. Chiral and
      guanidinylated hybrids exhibited the fastest killing effects against slow-growing
      cells and had more favourable antibiofilm properties than analogues only
      containing lysine or lacking chirality in the beta-peptoid residues. However, the
      results of the mature biofilm killing assay indicated more complex structure
      activity relationships. Cytotoxicity assays showed a clear correlation between
      oligomer length and cell toxicity within each subclass of peptides, but all
      possessed a high differential toxicity favouring killing of bacterial cells. This
      class of peptidomimetics may constitute promising antimicrobial alternatives for
      the prevention and treatment of multidrug-resistant S. epidermidis infections.

PMID- 23153958
TI  - New insights into replisome fluidity during chromosome replication.
AB  - Several paradigm shifting advances have recently been made on the composition and
      function of the chromosomal DNA replication machinery. Replisomes appear to be
      more fluid and dynamic than ever imagined, enabling rapid and efficient bypass of
      roadblocks and template lesions while faithfully replicating chromosomal DNA.
      This fluidity is determined by many layers of regulation, which reach beyond the
      role of replisome components themselves. In fact, recent studies show that
      additional polymerases, post-transcriptional modifications, and chromatin
      structure are required for complete chromosome duplication. Many of these factors
      are involved with the more complex events that take place during lagging-strand
      synthesis. These, and other recent discoveries, are the focus of this review.

PMID- 23153962
TI  - beta-Lactam therapeutic drug monitoring in the critically ill: optimising drug
      exposure in patients with fluctuating renal function and hypoalbuminaemia.
AB  - beta-Lactams are routinely prescribed in the treatment of serious infections.
      Empirical dosing schedules are typically derived from studies in healthy
      volunteers and largely fail to consider the significant changes in antibacterial
      pharmacokinetics often encountered in the critically ill. These changes are
      primarily driven by the underlying pathophysiology and the interventions
      provided, leading to altered protein binding, poor tissue penetration, and
      fluctuations in the volume of distribution and drug clearance. Each separately,
      and in combination, is likely to complicate successful beta-lactam administration
      in this setting. Although antibacterial therapeutic drug monitoring (TDM) has
      traditionally been employed to minimise drug toxicity, the challenges to
      achieving 'optimal' drug concentrations in the critically ill suggest beta-lactam
      TDM as an attractive means to optimise drug exposure. Whilst there is currently
      little evidence to support routine widespread application of such a service, beta
      lactam TDM may still have a role in select patients where difficulty in
      establishing therapeutic concentrations can be illustrated. This series utilises
      three representative cases from a beta-lactam TDM service that highlight the
      utility of this intervention in optimising antibacterial dosing. These
      preliminary data support an expanding role for beta-lactam TDM in select
      critically ill patients and provide insight into the subpopulations most at risk
      of suboptimal drug exposure. Future studies investigating the clinical outcome
      benefits of beta-lactam TDM in these patient groups are now warranted.

PMID- 23153963
TI  - Randomised clinical trial of moxifloxacin versus ertapenem in complicated intra
      abdominal infections: results of the PROMISE study.
AB  - Antibiotic therapy for complicated intra-abdominal infections (cIAIs) should
      provide broad-spectrum coverage both Gram-positive and Gram-negative
      microorganisms. The PROMISE study compared the clinical and bacteriological
      efficacy and safety of moxifloxacin versus ertapenem for the treatment of cIAIs.
      This randomised, prospective, double-dummy, double-blind, multicentre trial was
      designed as a non-inferiority study. The safety and efficacy of 5-14 days of
      daily intravenous moxifloxacin (400mg) or ertapenem (1g) were compared in
      patients with cIAIs requiring surgery and parenteral antibiotic therapy. The
      primary and secondary endpoints included clinical and bacteriological responses
      at 21-28 days after the end of treatment (TOC), respectively. Of 830 enrolled
      patients, 699 were efficacy valid. Moxifloxacin was non-inferior to ertapenem
      regarding clinical success [89.5% (315/352) versus 93.4% (324/347); 95%
      confidence interval (CI) -7.9%, 0.4%]. There were no significant differences
      between groups for any of the primary causes or types of cIAI regarding clinical
      response. Bacteriological success was achieved in 86.5% (257/297) of moxifloxacin
      treated patients and 90.2% (249/276) of ertapenem-treated patients (95% CI -9.0%,
      1.5%). There were no major differences between groups regarding the frequency or
      types of organisms eradicated. The incidence of adverse events (AEs) was higher
      with moxifloxacin than ertapenem (P=0.039), however a similar number of drug
      related AEs was seen in each group (P=1.000). Wound infections, nausea and
      increased lipase were the most commonly reported AEs with both agents. The
      results show that moxifloxacin is a valuable treatment option for a range of
      community-acquired cIAIs with mild-to-moderate severity.

PMID- 23153964
TI  - Basal ganglia-cortical interactions in Parkinsonian patients.
AB  - Parkinson's disease is a common and debilitating condition, caused by aberrant
      activity in a complex basal ganglia-thalamocortical circuit. Therapeutic advances
      rely on characterising interactions in this circuit. However, recording
      electrophysiological responses over the entire circuit is impractical. Dynamic
      causal modelling offers large-scale models of predictive value based on a limited
      or partial sampling of complex networks. Using dynamic causal modelling, we
      determined the network changes underlying the pathological excess of beta
      oscillations that characterise the Parkinsonian state. We modelled data from five
      patients undergoing surgery for deep brain stimulation of more than one target.
      We found that connections to and from the subthalamic nucleus were strengthened
      and promoted beta synchrony, in the untreated compared to the treated
      Parkinsonian state. Dynamic causal modelling was able to replicate the effects of
      lesioning this nucleus and may provide a new means of directing the search for
      therapeutic targets. 

PMID- 23153965
TI  - Identification of a strategic brain network underlying processing speed deficits
      in vascular cognitive impairment.
AB  - Patients with vascular cognitive impairment (VCI) commonly exhibit deficits in
      processing speed. This has been attributed to a disruption of frontal-subcortical
      neuronal circuits by ischemic lesions, but the exact mechanisms and underlying
      anatomical structures are poorly understood. We set out to identify a strategic
      brain network for processing speed by applying graph-based data-mining techniques
      to MRI lesion maps from patients with small vessel disease. We studied 235
      patients with CADASIL, a genetic small vessel disease causing pure VCI. Using a
      probabilistic atlas in standard space we first determined the regional volumes of
      white matter hyperintensities (WMH) and lacunar lesions (LL) within major white
      matter tracts. Conditional dependencies between the regional lesion volumes and
      processing speed were then examined using Bayesian network analysis. Exploratory
      analysis identified a network of five imaging variables as the best determinant
      of processing speed. The network included LL in the left anterior thalamic
      radiation and the left cingulum as well as WMH in the left forceps minor, the
      left parahippocampal white matter and the left corticospinal tract. Together
      these variables explained 34% of the total variance in the processing speed
      score. Structural equation modeling confirmed the findings obtained from the
      Bayesian models. In summary, using graph-based models we identified a strategic
      brain network having the highest predictive value for processing speed in our
      cohort of patients with pure small vessel disease. Our findings confirm and
      extend previous results showing a role of frontal-subcortical neuronal circuits,
      in particular dorsolateral prefrontal and cingulate circuits, in VCI. 

PMID- 23153967
TI  - Single subject fMRI test-retest reliability metrics and confounding factors.
AB  - While the fMRI test-retest reliability has been mainly investigated from the
      point of view of group level studies, here we present analyses and results for
      single-subject test-retest reliability. One important aspect of group level
      reliability is that not only does it depend on between-session variance (test
      retest), but also on between-subject variance. This has partly led to a debate
      regarding which reliability metric to use and how different sources of noise
      contribute to between-session variance. Focusing on single subject reliability
      allows considering between-session only. In this study, we measured test-retest
      reliability in four behavioural tasks (motor mapping, covert verb generation,
      overt word repetition, and a landmark identification task) to ensure
      generalisation of the results and at three levels of data processing (time-series
      correlation, t value variance, and overlap of thresholded maps) to understand how
      each step influences the other and how confounding factors influence reliability
      at each of these steps. The contributions of confounding factors (scanner noise,
      subject motion, and coregistration) were investigated using multiple regression
      and relative importance analyses at each step. Finally, to achieve a fuller
      picture of what constitutes a reliable task, we introduced a bootstrap technique
      of within- vs. between-subject variance. Our results show that (i) scanner noise
      and coregistration errors have little contribution to between-session variance
      (ii) subject motion (especially correlated with the stimuli) can have detrimental
      effects on reliability (iii) different tasks lead to different reliability
      results. This suggests that between-session variance in fMRI is mostly caused by
      the variability of underlying cognitive processes and motion correlated with the
      stimuli rather than technical limitations of data processing.

PMID- 23153966
TI  - The impact of visual acuity on age-related differences in neural markers of early
      visual processing.
AB  - The extent to which age-related differences in neural markers of visual
      processing are influenced by changes in visual acuity has not been systematically
      investigated. Studies often indicate that their subjects had normal or corrected
      to-normal vision, but the assessment of visual acuity seems to most frequently be
      based only on self-report. Consistent with prior research, to be included in the
      current study, subjects had to report normal or corrected-to-normal vision.
      Additionally, visual acuity was formally tested using a Snellen eye chart. Event
      related potentials (ERPs) were studied in young adults (18-32years old), young
      old adults (65-79years old), and old-old adults (80+ years old) while they
      performed a visual processing task involving selective attention to color. Age
      related differences in the latency and amplitude of ERP markers of early visual
      processing, the posterior P1 and N1 components, were examined. All results were
      then re-analyzed after controlling for visual acuity. We found that visual acuity
      declined as a function of age. Accounting for visual acuity had an impact on
      whether older and younger adults differed significantly in the size and latency
      of the posterior P1 and N1 components. After controlling for visual acuity, age
      related increases in P1 and N1 latency did not remain significant, and older
      adults were found to have a larger P1 amplitude than young adults. Our results
      suggest that until the relationship between age-associated differences in visual
      acuity and early ERPs is clearly established, investigators should be cautious
      when interpreting the meaning of their findings. Self-reports about visual acuity
      may be inaccurate, necessitating formal measures. Additional investigation is
      needed to help establish guidelines for future research, especially of very old
      adults.

PMID- 23153968
TI  - Expert individuation of objects increases activation in the fusiform face area of
      children.
AB  - The role of experience in the development of brain mechanisms for face
      recognition is intensely debated. Experience with subordinate- and individual
      level classification of faces is thought, by some, to be foundational in the
      development of the specialization of face recognition. Studying children with
      extremely intense interests (EII) provides an opportunity to examine experience
      related changes in non-face object recognition in a population where face
      expertise is not fully developed. Here, two groups of school-aged children -one
      group with an EII with Pokemon cards and another group of age-matched controls -
      underwent fMRI while viewing faces, Pokemon characters, Pokemon objects, and
      Digimon characters. Pokemon objects were non-character Pokemon cards that experts
      do not typically individuate during game play and trading. Neither experts nor
      controls had previous experience with Digimon characters. As expected, experts
      and controls showed equivalent activation in the fusiform face area (FFA) with
      face stimuli. As predicted by the expertise hypothesis, experts showed greater
      activation than controls with Pokemon characters, and showed greater activation
      with Pokemon characters than Pokemon objects. Experts and controls showed
      equivalent activation with Digimon characters. However, heightened activation
      with Digimon characters in both groups suggested that there are other strong
      influences on the activation of the FFA beyond stimulus characteristics,
      experience, and classification level. By demonstrating the important role of
      expertise, the findings are inconsistent with a purely face-specific account of
      FFA function. To our knowledge, this is the first demonstration of the effects of
      expertise and categorization level on activation in the FFA in a group of
      typically developing children.

PMID- 23153969
TI  - Evaluation and calibration of functional network modeling methods based on known
      anatomical connections.
AB  - Recent studies have identified large scale brain networks based on the spatio
      temporal structure of spontaneous fluctuations in resting-state fMRI data. It is
      expected that functional connectivity based on resting-state data is reflective
      of - but not identical to - the underlying anatomical connectivity. However,
      which functional connectivity analysis methods reliably predict the network
      structure remains unclear. Here we tested and compared network connectivity
      analysis methods by applying them to fMRI resting-state time-series obtained from
      the human visual cortex. The methods evaluated here are those previously tested
      against simulated data in Smith et al. (Neuroimage, 2011). To this end, we
      defined regions within retinotopic visual areas V1, V2, and V3 according to their
      eccentricity in the visual field, delineating central, intermediate, and
      peripheral eccentricity regions of interest (ROIs). These ROIs served as nodes in
      the models we study. We based our evaluation on the "ground-truth", thoroughly
      studied retinotopically-organized anatomical connectivity in the monkey visual
      cortex. For each evaluated method, we computed the fractional rate of detecting
      connections known to exist ("c-sensitivity"), while using a threshold of the 95th
      percentile of the distribution of interaction magnitudes of those connections not
      expected to exist. Under optimal conditions - including session duration of
      68min, a relatively small network consisting of 9 nodes and artifact-free
      regression of the global effect - each of the top methods predicted the expected
      connections with 67-85% c-sensitivity. Correlation methods, including Correlation
      (Corr; 85%), Regularized Inverse Covariance (ICOV; 84%) and Partial Correlation
      (PCorr; 81%) performed best, followed by Patel's Kappa (80%), Bayesian Network
      method PC (BayesNet; 77%), General Synchronization measures (67-77%), and
      Coherence (CohB; 74%). With decreased session duration, these top methods saw
      decreases in c-sensitivities, achieving 59-76% for 17min sessions. With a short
      resting-state fMRI scan of 8.5min, none of the methods predicted the real network
      well, with Corr (65%) performing best. With increased complexity of the network
      from 9 to 36 nodes, multivariate methods including PCorr and BayesNet saw a
      decrease in performance. Artifact-free regression of the global effect increased
      the c-sensitivity of the top-performing methods. In an overall evaluation across
      all tests we performed, correlation methods (Corr, ICOV, and PCorr), Patel's
      Kappa, and BayesNet method PC set themselves somewhat above all other methods. We
      propose that data-based calibration based on known anatomical connections be
      integrated into future network studies, in order to maximize sensitivity and
      reduce false positives.

PMID- 23153971
TI  - Carbapenem-resistant Klebsiella pneumoniae harbouring blaKPC-3 and blaVIM-2 from
      central Italy.
AB  - The frequency of Klebsiella pneumoniae carbapenemase-producing K. pneumoniae is
      increasing in Italian hospitals and poses an emerging threat to the management of
      infections in hospitalized patients. In this study, we report a detailed
      molecular characterization of a K. pneumoniae subsp. pneumoniae KP1/11 isolate
      from the decubitus ulcer of a hospitalized patient with a serious infection. K.
      pneumoniae KP1/11 produces KPC-3 and VIM-2 beta-lactamases. The bla(KPC-3) gene
      is harbored in a large plasmid in a complex structure of Tn3-based transposon,
      Tn4401a. The chromosomal DNA of K. pneumoniae harbored also 2 class 1 integrons
      with different variable regions: 1) orfD-aacA8; 2) aacA29-bla(VIM-2).

PMID- 23153970
TI  - Unbiased tensor-based morphometry: improved robustness and sample size estimates
      for Alzheimer's disease clinical trials.
AB  - Various neuroimaging measures are being evaluated for tracking Alzheimer's
      disease (AD) progression in therapeutic trials, including measures of structural
      brain change based on repeated scanning of patients with magnetic resonance
      imaging (MRI). Methods to compute brain change must be robust to scan quality.
      Biases may arise if any scans are thrown out, as this can lead to the true
      changes being overestimated or underestimated. Here we analyzed the full MRI
      dataset from the first phase of Alzheimer's Disease Neuroimaging Initiative (ADNI
      1) from the first phase of Alzheimer's Disease Neuroimaging Initiative (ADNI-1)
      and assessed several sources of bias that can arise when tracking brain changes
      with structural brain imaging methods, as part of a pipeline for tensor-based
      morphometry (TBM). In all healthy subjects who completed MRI scanning at
      screening, 6, 12, and 24months, brain atrophy was essentially linear with no
      detectable bias in longitudinal measures. In power analyses for clinical trials
      based on these change measures, only 39AD patients and 95 mild cognitive
      impairment (MCI) subjects were needed for a 24-month trial to detect a 25%
      reduction in the average rate of change using a two-sided test (alpha=0.05,
      power=80%). Further sample size reductions were achieved by stratifying the data
      into Apolipoprotein E (ApoE) epsilon4 carriers versus non-carriers. We show how
      selective data exclusion affects sample size estimates, motivating an objective
      comparison of different analysis techniques based on statistical power and
      robustness. TBM is an unbiased, robust, high-throughput imaging surrogate marker
      for large, multi-site neuroimaging studies and clinical trials of AD and MCI.

PMID- 23153972
TI  - Genetic association of adiponectin gene polymorphisms (+45T/G and +10211T/G) with
      type 2 diabetes in North Indians.
AB  - Adiponectin (ADIPOQ) is an abundant protein hormone which belongs to a family of
      so-called adipokines. It is expressed mostly by adipocytes and is an important
      regulator of lipid and glucose metabolism. It was shown that decreased serum
      adiponectin concentration indicated insulin resistance and type 2 diabetes (T2DM)
      with the risk of cardiovascular complications. The fact that adiponectin is an
      insulin-sensitizing hormone with anti-diabetic, anti-inflammatory and anti
      atherogenic properties, we proposed to study the association of ADIPOQ gene
      polymorphisms in subjects with T2DM. DNA was isolated from venous blood samples,
      quantified and subjected to Polymerase Chain Reaction-Restriction Fragment Length
      Polymorphism (PCR-RFLP) using suitable primers and restriction endonucleases.
      Adiponectin levels were measured in serum using ELISA. The genotypic, allelic and
      carriage rate frequencies distribution in patients and controls were analyzed by
      PSAW software (ver. 17.0). Odd ratios (OR) with 95% confidence interval (CI) were
      determined to describe the strength of association by logistic regression model.
      Out of the two polymorphisms studied, +10211T/G showed significant association
      (P=0.042), the 'G' allele association being highly significant (P=0.022). Further
      analysis showed that individuals with 'GG' haplotype were at increased risk of
      T2DM up to 15.5 times [P=0.015, OR (95% CI); 15.558 (1.690-143.174)]. The present
      study showed that the 'G' allele of ADIPOQ gene (+10211T/G) plays a prominent
      role with respect to T2DM susceptibility in North-Indian population.

PMID- 23153974
TI  - Targeting tumor necrosis factor alpha (TNF-alpha) in diabetic rats could approve
      avenues for an efficient strategy for diabetic therapy.
AB  - BACKGROUND: Several studies held belief that downregulation of TNF-alpha may be
      effective for preventing diabetes and it's complications. However, it is not
      known whether TNF-alpha downregulation in long-term can generate any biological
      adverse. AIM: The aim of the present study was to clarify what the impact is for
      such treatment with specific antibody for TNF-alpha on the other biological
      activities after 4weeks. METHODS: Using western blot, IHC, Elisa, biochemical
      assays and scanning electron microscope. RESULTS: Results show that TNF-alpha,
      FOXO-1, IL-6 and MPO, when expressed in diabetic rats, collectively induce
      dramatic changes in diabetic rats. Since, TNF-alpha is involved in activation of
      transcription factor FOXO1 along with oxidative stress mediated by neutrophils.
      On one hand, IL-6 mediates neutrophils activation leading to an augmentation in
      stress mediators. And FOXO1 is activated in order to eliminate these oxidative
      mediators, on the other hand. Data show also that the prominent defect in mucosal
      IgA and IL-2 secretions may be the leading reasons for digestive atrophy.
      Finally, Akt-1 inhibits the cleavage of caspase 3, so, it could prevent the
      incidence of apoptosis. CONCLUSION: Findings of this study reveal how TNF-alpha
      can be mechanistically coupled to greater diabetic complications potential.

PMID- 23153973
TI  - Clinical profile of coexisting conditions in type 1 diabetes mellitus patients.
AB  - AIMS: Type 1 diabetes mellitus (T1DM) is associated with various genetic and
      autoimmune diseases implicated in its etiopathogenesis. We hereby profile the
      clinical association of such diseases among patients from our center. METHODS:
      Consecutive patients of T1DM presenting to department of Endocrinology from May
      1997 to December 2011 were retrospectively analyzed in context of associated
      clinical profile. RESULTS: Among 260 patients diagnosed as T1DM, 21 (8%) had
      hypothyroidism, 4 (1.5%) had hyperthyroidism and 2 (0.7%) had primary adrenal
      insufficiency. Eighteen patients (7%) had celiac disease, 9 (3.5%) had Turner's
      syndrome, 5 patients (1.9%) had Klinefelter's syndrome, whereas Down's syndrome
      and Noonan's syndrome was present in 2 and 1 patients (0.7%) respectively. One
      patient had Wolframs' syndrome and 1 patients had myasthenia gravis. Systemic
      lupus erythematosus and rheumatoid arthritis were present in 3 and 1 patients
      respectively. Total of 5 patients with cerebral palsy, 4 cases with deaf mutism,
      4 cases with acute psychosis and 16 patients with depression were noted. Mean age
      of study patients was 20.8+/-9.8 years (range, 3-23 years). CONCLUSION: Various
      conditions including genetic (Down, Turner, Noonan, and Klinefelter's),
      autoimmune (thyroid and adrenal disorders, myasthenia gravis, SLE, rheumatoid
      arthritis) and central nervous system diseases were the associated diseases
      encountered in our patients. Routine screening is required for early diagnosis
      and treatment of associated co morbidities.

PMID- 23153975
TI  - Quantitative vibration perception threshold in assessing diabetic neuropathy: is
      the cut-off value lower for Indian subjects? [Q-VADIS Study].
AB  - AIMS: The aim was to compute a normative data of VPT [Vibration Perception
      Threshold], compare results of VPT among type 2 diabetes patients with and
      without neuropathy, validate VPT taking NDS [Neuropathy Disability Scores] as
      gold standard and suggest a cut off value for the Indian population. MATERIALS
      AND METHODS: A clinic based case-control study was conducted at Nightingale
      Hospital (NH) in Kolkata for 2 months duration. Fifty type 2 diabetes patients
      (who were detected with by fasting plasma glucose or on medication) reporting at
      OPD (Out Patent Department) were randomly selected and informed consent was
      obtained. The age range was 20-65 years and other common causes of neuropathy
      were excluded. Same number of control patients without diabetes and reporting at
      the same hospital during the study period in the similar age range were selected.
      RESULTS: The normative data of VPT for mean of 4 sites (malleoli and great toe)
      was 11.3+/-4.9mV. The VPT value was significantly higher among diabetic patients
      with neuropathy compared to non-neuropathic and non-diabetic patients.
      Considering NDS score as gold standard lowering the cutoff value of VPT from 25mV
      to 20mV increased the sensitivity from 50% to 62.5% in detecting diabetic
      neuropathy compared to NDS taken as a gold standard. CONCLUSIONS: It was found
      that lowering the cut off value of VPT in Indian population increased the
      sensitivity of the test to detect diabetic neuropathy without hampering the
      specificity. There is however no indication that a lower cut off VPT value is
      justified as of now.

PMID- 23153976
TI  - Relationship of RIC-3 gene rs1528133 polymorphism with varying degrees of body
      weight and eating behavior.
AB  - AIMS: The aim of this study was to determine the allele frequencies of resistance
      to inhibitors of cholinesterase 3 homologue (RIC-3) gene rs1528133 polymorphism
      in overweight+obese+morbid obese and non-obese (non-OB) subjects. The effects of
      rs1528133 genotypes on anthropometric, diabetes and obesity related parameters,
      self-reported macronutrient intake and drugs were also evaluated. The study was
      performed on overweight+obese+morbid obese and non-obese subjects. METHODS: RIC-3
      gene rs1528133 genotypes were determined with qPCR. RESULTS: The RIC-3 rs1528133
      genotype frequencies were respectively as 89.4% for homozygous wild type (A/A),
      10.6% for heterozygous (A/C) genotypes in overweight+obese+morbid obese patients
      and 92.7% for A/A, 7.3% for A/C genotypes in non-OB subjects. The homozygous
      mutant genotype (C/C) was not detected in our study population. Genotype
      frequencies were not significantly different among study groups. Heterozygous
      genotype carriers for the rs1528133 polymorphism were found to prefer higher
      glycemic load, fat and protein diet content compared to homozygous wild type
      genotype carriers (p=0.0001). The frequency of rs1528133 heterozygous individuals
      (16.7%) using antihypertensive drugs was lower (p=0.045) in comparison to wild
      type genotype carriers (46.9%) in the whole study population. CONCLUSIONS: RIC-3
      gene rs1528133 variation was not found to be effective over any analyzed obesity
      related parameter, but associated with higher glycemic load, protein and fat
      eating behavior and antihypertensive drug use.

PMID- 23153977
TI  - Prevalence and risk factors for diabetes and impaired glucose tolerance in Asian
      Indians: a community survey from urban eastern India.
AB  - OBJECTIVES: To determine the prevalence of diabetes and impaired glucose
      tolerance (IGT) and to identify risk factors for the same specific to an
      underdeveloped urban locale of Eastern India. METHODS: Study design. Population
      based cross-sectional study, with multistage random sampling technique. Setting.
      Urban city-dwellers in Orissa one of the poorest states of Eastern India
      bordering a prosperous state of Andhra Pradesh of Southern India. Participants.
      1178 adults of 20-80 years age randomly selected from 37 electoral wards of urban
      populace. Definition and diagnosis of diabetes mellitus and IGT. These were based
      on a Report of a World Health Organization/International Diabetes Federation
      Consultation of 2006. Main outcome measure. Prevalence and significant risk
      factors for Diabetes and IGT. Statistical analysis. Both descriptive and
      multivariable logistic regression analyses. RESULTS: The crude rates of diabetes
      and IGT in the study population were 15.7% and 8.8%, respectively. Similarly age
      standardized rates of diabetes and IGT were 11.1% and 6.7%, respectively. Both
      diabetes and IGT had shown a male preponderance. CONCLUSION: Diabetes and IGT
      were very highly prevalent in this urban populace. Cardiometabolic risk factors
      like older age, central obesity, inadequate fruit intake, hypertension,
      hypertriglyceridemia and socio economic status were found to be significant
      predictors of diabetes in this study.

PMID- 23153978
TI  - Influence of iron metabolism indices on HbA1c in non-diabetic pregnant women with
      and without iron-deficiency anemia: effect of iron supplementation.
AB  - AIMS: Condition that influence erythrocyte turnover also affect HbA1c. Although
      many forms of anemia are associated with lowering of HbA1c, iron-deficiency
      anemia (IDA) tends to increase HbA1c. In this study, we examined the relationship
      between HbA1c and erythrocyte indices in non-diabetic pregnancy and assessed the
      effect of iron supplementation on HbA1c. MATERIALS AND METHODS: 150 women were
      studied (30 non-diabetic), non-pregnant, non-anemic women in child bearing women
      with varying parity as controls (Gp 1); 30 non-diabetic, non-anemic pregnant
      women in first trimester of pregnancy (Gp 2a); 30 non-diabetic, non-anemic
      pregnant women in second trimester of pregnancy (Gp 2b); 30 non-diabetic, non
      anemic pregnant women in third trimester of pregnancy (Gp 2c) and 30 non-diabetic
      pregnant women with IDA (Gp 2d). HbA1c, OGTT, erythrocyte indices and iron
      metabolic indices were determined in Gp 2d subjects not supplemented with iron
      and repeated these indices after 3 months of iron-supplementation. RESULTS: The
      mean fasting and postprandial blood glucose levels (79.9+/-8.0mg/dl, 108.1+/
      14.1mg/dl) in Gp 1 were found to be significantly lower in first trimester among
      Gp 2a (74.4+/-5.3mg/dl and 97.2+/-11.1mg/dl), in second trimester among Gp 2b
      (76.2+/-5.2mg/dl and 103.4+/-7.9mg/dl) followed by increase in IIIrd trimester
      among Gp 2c (82.3+/-5.7mg/dl and 112.5+/-8.5mg/dl) subjects. A significant
      difference in HbA1c was also observed among the groups (HbA1c 4.7+/-0.3% in Gp 1;
      4.6+/-0.4% in Gp 2a; 4.5+/-0.3 in Gp 2b; 4.7+/-0.3 in Gp 2c). Among Gp 2d
      subjects, HbA1c was 5.2+/-0.3% and the level decreased after iron supplementation
      to 5.1+/-0.3%. Significant correlation between erythrocyte indices, iron
      metabolic indices and HbA1c was also observed. CONCLUSION: We conclude that
      consideration should be given for performing glucose testing in patients with IDA
      to ascertain the reliability of HbA1c in the diagnosis of diabetes. HbA1c
      concentrations in diabetic patients with IDA should be interpreted with caution.

PMID- 23153979
TI  - Endothelial nitric oxide synthase Glu298Asp (G894T) gene polymorphism in coronary
      artery disease patients with type 2 diabetes mellitus.
AB  - AIMS: Endothelial dysfunction is thought to be a significant risk factor for
      cardiovascular disease. This study determined the role of endothelial nitric
      oxide synthase (eNOS) Glu298Asp polymorphism and intergenotypic variation of
      plasma nitric oxide (NO) levels in coronary artery disease (CAD) patients with
      type 2 diabetes mellitus (DM). METHODS: This case-control study included 28
      documented CAD patients with type 2 DM and 32 non-diabetic patients with CAD.
      Fifty healthy volunteers without any major cardiovascular risk factors served as
      controls. NO was estimated by modified Griess method. The eNOS gene polymorphism
      was studied by amplifying DNA by PCR and digesting with BanII restriction enzyme.
      Restriction fragment length polymorphism was studied by using a gel documentation
      system. RESULTS: The genotype frequencies for Glu298Asp (GT) genotype were 10.71%
      in diabetic CAD patients, 28.1% in non-diabetic CAD patients and 12% in controls.
      The T allele frequency was higher in the non-diabetic CAD group (14%) as compared
      with the diabetic CAD (5.4%) and control group (6%). NO level was significantly
      lower in non-diabetic CAD patients (10.25 mmol/L) but not in diabetic CAD
      patients (13.89 mmol/L) as compared to controls (16.78 mmol/L). CONCLUSION:
      Glu298Asp polymorphism is not the mediator of increased incidence of CAD in
      diabetic patients.

PMID- 23153980
TI  - Hemoglobin A1C determination by point-of-care testing: its correlation to
      standard method.
AB  - The hemoglobin A1C (HbA1C) is the useful test for following up of glycemic
      control of the diabetic patient. Due to the present advance in point-of-care
      testing (POCT) technology, the new POCT for determination of HbA1C is available.
      Here, the author performs a laboratory comparative study between the new POCT
      tool (DCA) and classical tool (COBAS) for analysis of HbA1C level. This study is
      the second confirmation study in Thailand performed in the new setting adding to
      the previous author's report. The results show that there is a good correlation
      between two techniques and the error of the POCT tool is within acceptable limit.

PMID- 23153981
TI  - Oral mucositis, Steven Johnson syndrome and amlodipine usage in a case with
      metabolic syndrome.

PMID- 23153982
TI  - Mechanisms and techniques of reprogramming: using PDX-1 homeobox protein as a
      novel treatment of insulin dependent diabetes mellitus.
AB  - Homeobox proteins are key regulators of stem cell proliferation and
      differentiation which function as transcription factors and regulate cell fate
      decisions. Pancreatic Duodenal Homeobox-1 (PDX-1) is a homeobox protein which
      acts as a key regulator in the development of b cells in the Islets of
      Langerhans. It plays an important role in maintaining the identity and function
      of the Islets of Langerhans, and in the development of the pancreas. There is
      strong evidence that PDX-1 plays a role in activating the insulin promoter and
      increasing insulin levels in response to glucose. PDX-1 also binds to sequences
      within beta cells and regulates the promoter activity of a number of islet genes
      including insulin, glut-2 and neurogenin 3. When fused with the VP16 activation
      sequence, transfection of the PDX-1 gene has been shown to transform liver cells
      into insulin producing cells. Because homeobox proteins are able to passively
      translocate through cell membranes, due to an intrinsic transduction domain
      (penetratin), the use of these proteins to reprogram target cells may help
      overcome the limiting supply of beta cells and be a potential future treatment
      for Type 1 diabetes.

PMID- 23153983
TI  - Visfatin and its role in obesity development.
AB  - Visfatin, a product of PBEF gene, is an adipocytokine that harbours strong
      insulin-mimetic activity and it has been reported previously to associate with
      obesity. Recent reports also provide evidence that Visfatin has also important
      intracellular effects as it is homologous with nicotinamide
      phosphoribosyltransferase (NAMPT). In this review, we summarize the main
      documented effects of Visfatin on metabolism in humans, with special emphasis put
      on the pathways associated with obesity.

PMID- 23153984
TI  - Prospective monitoring N-terminal pro-brain natriuretic peptide during natural
      progression of atherosclerotic renal artery stenosis in elderly.
AB  - Prognostic values of N-terminal pro-brain natriuretic peptide (NT-proBNP) in
      myriad diseases have been studied. During the natural progression of
      atherosclerotic renal artery disease (ARVD) changes of NT-proBNP levels and its
      significance is not understood. A prospective longitudinal follow-up study was
      conducted among 61 ARVD patients (77.7 +/- 5.2 years old). NT-proBNP was
      determined at baseline and six month intervals over 25.89 +/- 12.44 months and
      its correlation with death and/or newly occurred CVEs were assessed. Level of NT
      proBNP increased from baseline median 210.0 pg/mL (25th-75th percentile, 98.0
      pg/mL-540.0 pg/mL) to 900.9 pg/mL (25th-75th percentile, 704.5 pg/mL-1583.5
      pg/mL) (p=0.032) at the end of follow-up. Among 44.26% of the cohort (n=27) NT
      proBNP level >=450 pg/mL was detected, which 6 deaths happened (22.22% death
      rate) and CVEs occurred to 62.96% of patients, comparing to 0% death rate
      (p=0.077) and 8.82% affected by CVEs (p=0.019) in other 55.74% of cohort (n=34)
      whose NT-proBNP <450 pg/mL. Kaplan-Meier analysis showed that NT-proBNP level
      >=450 pg/mL was a risk factor related to CVEs (HR=3.96, p=0.03). Cox regression
      analysis found NT-proBNP level >=450 pg/mL was an independent risk factor of CVEs
      (HR=5.12, p=0.022) after adjustment of body mass index, blood pressure, kidney
      function. The negative predictive value was 90.9% of NT-proBNP levels >=450 pg/mL
      for new CVEs. NT-proBNP levels diverge throughout ARVD natural progression in
      elderly males over 75 years of age. Elevated NT-proBNP level of >=450 pg/mL was
      predictive for CVEs with 90.9% of negative predictive value.

PMID- 23153985
TI  - Gender differences in factors influencing sexual satisfaction in Korean older
      adults.
AB  - This study investigates the sex lives of Korean older adults (i.e., those over 60
      years) and attempts to identify gender-related factors influencing sexual
      satisfaction. It used data from the 2008 Korean National Survey on Older Adults
      conducted by the Ministry of Health, Welfare, and Families. Of the 15,146
      individuals who had taken part in the 2008 study, secondary analysis was
      conducted with data from 3360 persons who had spouses and were willing to respond
      to sex-related questions in a face-to-face interview. The mean age of male and
      female subjects was 67.34 and 66.86 years respectively. In the male subjects,
      sexual frequency, followed by marital satisfaction and cognitive function, had
      the greatest effect on sexual satisfaction. These three variables together
      accounted for 21% of the male subjects' sexual satisfaction. In the female
      subjects, marital satisfaction, followed by frequency of sexual activity, absence
      of depressive symptoms, age, and length of cohabitation with spouse, had the
      greatest effect on sexual satisfaction. These five variables together explained
      11% of their sexual satisfaction. This study indicates that sexual frequency and
      physical factors have the most important effects on the sex lives of older men,
      while older women value psychosocial and relational factors more highly.
      Therefore, interventions aiming to improve sexual satisfaction in older adults
      should take gender differences into account.

PMID- 23153986
TI  - [18F-FDG PET/CT diagnosis of liver cyst infection in a patient with autosomal
      dominant polycystic kidney disease and fever of unknown origin].
AB  - The diagnosis, localization and treatment of infected cysts in the kidney or
      liver of patients with autosomal dominant polycystic kidney disease (ADPKD)
      remain a clinical challenge. We report the findings of (18)F-FDG PET-CT in an
      ADPKD diagnosed patient who required renal transplantation five years before and
      in his follow up presented repeated episodes of bacteriemia without known focus
      on radiological tests performed. The (18)F-FDG PET-CT scan showed numerous
      hypermetabolic images with focal or ring-shaped morphology related to the content
      and the wall of some hepatic cysts. The increased metabolic activity was
      localized on segments VI and VII. We proceeded to drainage of one cyst in segment
      VI, removing 110 cc of purulent fluid which grew E. Coli BLEE. The (18)F-FDG
      PET/CT scan should be included in the diagnostic algorithm for detecting infected
      liver cysts in patients with ADPKD and fever of unknown origin.

PMID- 23153987
TI  - Application of 99mTc-denatured red blood cells scintigraphy in the evaluation of
      post-traumatic spleen auto-transplantation.

PMID- 23153988
TI  - Fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT)
      for the detection of skeletal muscle and skin metastases in uterine
      leiomyosarcoma: a case report.
AB  - We report the clinical value of FDG PET/CT imaging in a 57-year-old woman who was
      diagnosed with uterine leimyosarcoma 6 years ago. In a staging procedure, whole
      body FDG PET/CT discloses the presence of both local recurrence and remote
      metastases at widespread musculocutaneous sites, liver and femur. With its
      advantage of scanning the whole body in a single procedure, we propose the use of
      PET/CT imaging for the evaluation of patients with uterine leimyosarcomas, a
      tumor with a propensity for widespread hematogenous spread to unusual sites. 

PMID- 23153989
TI  - Gestational diastolic hypertension with gene mutation-related pheochromocytoma
      positive at 18F-DOPA PET/CT: diagnostic and therapeutic implications.

PMID- 23153990
TI  - PPARgamma regulates the mitochondrial dysfunction in human neural stem cells with
      tumor necrosis factor alpha.
AB  - Peroxisome proliferator-activated receptor gamma (PPARgamma) belongs to a family
      of ligand-activated transcription factors, and its ligands are known to control
      many physiological and pathological conditions. The hypothesis of our study was
      that the PPARgamma agonist (rosiglitazone) could mediate tumor necrosis factor
      alpha (TNFalpha) related to the regulation of human neural stem cells (hNSCs), by
      which TNFalpha possibly fulfills important roles in neuronal impairment. The
      results show that PPARgamma mediates the cell viability of hNSCs via the
      downregulation of the activity of caspase 3, indicating that this rescue effect
      of PPARgamma could improve the reduced levels of two mitochondrial regulators,
      adenosine monophosphate-activated protein kinase (AMPK) and Sirtuin 1 (SIRT1) in
      the hNSCs with TNFalpha. The stimulation of mitochondrial function by PPARgamma
      was associated with activation of the PPAR coactivator1 alpha (PGC1alpha) pathway
      by up-regulation of oxidative defense and mitochondrial systems. The above
      protective effects appeared to be exerted by a direct activation of the
      rosiglitazone, because it protected hNSCs from TNFalpha-evoked oxidative stress
      and mitochondrial deficiency. Here we show that the rosiglitazone protects hNSCs
      against Abeta-induced apoptosis and promotes cell survival. These findings extend
      our understanding of the central role of PPARgamma in TNFalpha-related neuronal
      impairment, which probably increases risks of neurodegenerative diseases. The
      anti-inflammatory effects of PPARgamma in the hNSCs with TNFalpha, and the
      involved mechanisms were also characterized.

PMID- 23153991
TI  - Differential regulation of CDK5 and c-Fos expression by morphine in the brain of
      Lewis and Fischer 344 rat strains.
AB  - The aim of this study was to comparatively study cyclin-dependent kinase 5 (CDK5)
      and c-Fos regulation by morphine in the brains of Lewis and Fischer 344 (F344)
      rats, which are known to differ in their behavioral sensitivities to several
      drugs of abuse. Two hours after an acute i.p. administration of morphine (10 mg
      kg(-1)) or saline (control), the animals were perfused and their brains prepared
      for immunohistochemistry. The number of CDK5 immunoreactive cells was
      significantly higher in the nucleus accumbens (NAC), the locus coeruleus (LC) and
      the nucleus tractus solitarius (NTS) of saline-injected F344 rats than in those
      of the Lewis rats. Morphine upregulated CDK5 with a varying pattern depending on
      the strain and brain area. The effect of the opioid was more marked in the NTS of
      the Lewis rats and the NAC of the F344 rats. Immunostaining of c-Fos was very low
      or absent in the control animals and was consistently up-regulated by morphine,
      especially in the LC and NTS of the F344 rats and the NAC of the Lewis rats. We
      propose that the acute morphine regulation of CDK5 expression in the NAC may
      predict the rate of drug intake and/or extinction of drug seeking, while the
      pattern of c-Fos activation may be more related to the differential acquisition
      of morphine-seeking behaviors.

PMID- 23153992
TI  - History of the New York Roentgen Society.

PMID- 23153994
TI  - Three-dimensional MRI with contrast diagnosis of diseases involving peripheral
      oculomotor nerve.
AB  - PURPOSE: The purpose was to evaluate three-dimensional magnetic resonance imaging
      with contrast (3D-CEMRI) in displaying peripheral oculomotor nerve (PON) and
      diagnosing peripheral oculomotor nerve diseases (POND). MATERIALS AND METHODS:
      The MRI findings of 80 patients with POND were reviewed and compared with digital
      subtraction angiography (DSA), operative or pathological results, and final
      clinical diagnosis. RESULTS: Twenty-three aneurysms (23/26) confirmed by DSA were
      detected with Magnetic Resonance Angiography (MRA). Twenty-five inflammatory
      lesions, 14 malignant lesions, and 5 benign lesions involving PON were shown with
      3D-CEMRI corresponding with clinical diagnosis and pathology. Another 13 (13/80,
      16.03%) cases were negative on MRI. CONCLUSION: 3D-CEMRI with MRA could show and
      diagnose the majority of the diseases involving PON.

PMID- 23153993
TI  - Spectrum of malignant renal and urinary bladder tumors on 18F-FDG PET/CT: a
      pictorial essay.
AB  - A wide variety of malignant renal and urinary bladder diseases can be detected on
      (18)F-FDG PET/CT. Although the PET/CT findings are often nonspecific, the aim of
      this atlas was to demonstrate that the spectrum of renal and urinary bladder
      malignancy that can be evaluated with PET/CT is much broader than current medical
      literature would suggest. PET/CT readers and oncologists should be aware of the
      variety of urological tumor types that can be detected on PET/CT and some of the
      patterns of (18)F-FDG uptake that can be observed in these cases.

PMID- 23153995
TI  - Role of perfusion CT in differentiating between various cerebral masses using
      normalized permeability surface area product and cerebral blood volume.
AB  - OBJECTIVE: The objective was to assess usefulness of a combined analysis using
      the perfusion computed tomography parameters permeability surface area product
      (PS) and cerebral blood volume (CBV) in the differential grouping of various
      cerebral masses. METHODS: Thirty patients who had a cerebral mass, confirmed by
      pathologic verification, were included. We classified PS and CBV results for
      various cerebral masses by visual as well as semiquantitative assessment. To
      verify statistically significant differences between the groups, one-way analysis
      of variance was performed. RESULTS: Patients were categorized into five groups
      with statistically significant differences (P<.01). CONCLUSIONS: PS and CBV were
      useful in the differential diagnosis of cerebral masses.

PMID- 23153996
TI  - Parathyroid adenoma screening efficacies of different imaging tools and factors
      affecting the success rates.
AB  - PURPOSE: We aimed to compare the efficacy of three different parathyroid adenoma
      screening tools--high-resolution ultrasonography (USG), technetium Tc 99m
      methoxyisobutylisonitrile (MIBI) parathyroid scintigraphy, and magnetic resonance
      imaging (MRI)--and we evaluated the factors affecting the detection success
      rates. METHODS: Parathyroid imaging was evaluated by USG, double-phase 99mTc-MIBI
      parathyroid scintigraphy, and cervical MRI in patients with hyperparathyroidism
      (n=39). RESULTS: Among the 39 patients, USG, parathyroid scintigraphy, and MRI
      correctly identified 35 adenomas (89.7%), 28 adenomas (71.8%), and 26 adenomas
      (66.7%), respectively. Positive predictive values for USG (34/35), scintigraphy
      (27/28), and cervical MR (26/26) imaging were 97.1%, 96%, and 100%, respectively.
      Parathyroid adenomas were detected with 92.3% (36/39) certainty when both USG and
      scintigraphy modalities were applied together. Minimally invasive
      parathyroidectomy under local anesthesia with unilateral incision was
      successfully performed in 24 (61.5%) patients. CONCLUSIONS: Minimally invasive
      surgery for parathyroid adenomas has been developed and has equal success with
      traditional surgery. However, accurate localization of adenomas should be
      obtained prior to surgery. In this study, ultrasound was found to be effective in
      localizing adenomas for successful surgery. Adding other imaging modalities does
      not improve localizing the parathyroid adenomas.

PMID- 23153997
TI  - Functional magnetic resonance imaging of methamphetamine craving.
AB  - The study aimed to explore the abnormal activation of special brain areas
      associated with methamphetamine craving using functional magnetic resonance
      imaging (fMRI) and to reveal the neurobiological basis of addiction. Twenty-six
      methamphetamine addicts and 26 healthy subjects were scanned by brain fMRI while
      watching pictures of happy, sad, or methamphetamine to acquire resource data.
      SPM5 was used to analyze fMRI data to get related brain activation map, and it
      was found that methamphetamine addicts had high brain activation in cingulate and
      low activation in frontal lobe when watching methamphetamine-cue pictures. This
      study demonstrated that methamphetamine addicts had emotion-related brain
      activation abnormalities.

PMID- 23153998
TI  - MRI and 1H-MRS on diagnosis of pineal region tumors.
AB  - PURPOSE: The purpose was to analyze characteristic magnetic resonance (MR)
      imaging of pineal region tumors and to explore the value of diffusion-weighted
      imaging (DWI) and (1)H-MR spectroscopy ((1)H-MRS) in differential diagnosis among
      four common solid diseases: germinoma, teratoma, pineoblastoma, and glioma.
      METHODS: Thirty-three patients with pineal region tumors proven by pathology were
      prospectively studied. All of them underwent MRI SE-T1WI, FSE-T2WI, fluid
      attenuated inversion recovery (FLAIR), and postcontrasted MR scan. Minimum
      apparent diffusion coefficient (ADC) value, and maximum MRS choline/N-acetyl
      aspartate (Cho/NAA) and lipid/creatine (Lip/Cr) metabolic peak-height ratios were
      quantified within each lesion. RESULTS: Most pineal region diseases have their
      typical morphology, signal intensity, and enhancement style. ADC values were
      lower in germinoma [(6.98+/-0.35)*10(-4)] and pineoblastoma [(9.14+/-0.79)*10(
      4)] than in teratoma [(2.80+/-0.18)*10(-3)] and pineal glioma [(1.63+/-0.66)*10(
      3)] (P<.05). Cho/NAA ratios were higher in germinoma (2.09+/-0.39), pineoblastoma
      (4.70+/-0.82), and pineal glioma (3.54+/-0.38) than in teratoma (1.52+/-0.91)
      (P<.05). Lip/Cr ratios were lower in germinoma (2.52+/-0.41) than in teratoma
      (8.47+/-1.16) (P<.05). CONCLUSIONS: Changes in morphologic features, signal
      intensity, and enhancement style are the most helpful variables for the
      differential diagnosis of pineal region tumors. To some extent, DWI and (1)H-MRS
      imaging enable distinction among them.

PMID- 23153999
TI  - Mammogram-based discriminant fusion analysis for breast cancer diagnosis.
AB  - Mammogram-based classification is an important and effective way for computer
      aided diagnosis (CAD)-based breast cancer diagnosis. In this paper, we present a
      novel discriminant fusing analysis (DFA)-based mammogram classification CAD-based
      breast cancer diagnosis. The discriminative breast tissue features are exacted
      and fused by DFA, and DFA achieves the optimal fusion coefficients. The largest
      class discriminant in the fused feature space is achieved by DFA for
      classification. Beside the detailed theory derivation, many experimental
      evaluations are implemented on Mammography Image Analysis Society mammogram
      database for breast cancer diagnosis.

PMID- 23154000
TI  - Combination of high-intensity focused ultrasound with nanoscale ultrasound
      contrast agent in treatment of rabbit breast VX2 tumors: a pilot study.
AB  - To demonstrate ultrasound contrast agents to be important potentiators of high
      intensity focused ultrasound (HIFU), we prospectively assessed the effectiveness
      of HIFU combined with nanoscale ultrasound contrast agents for the treatment of
      breast VX2 tumors in rabbits. We found that the change of grayscale value in the
      target area in the HIFU+nanobubble group was significantly higher than that in
      the HIFU+phosphate-buffered saline (PBS) group after irradiation (P<.01). The
      size of coagulation necrosis was also significantly larger in the HIFU+nanobubble
      group when compared to that in the HIFU+PBS group (P<.001). In conclusion, our
      study suggested that adding nanoscale ultrasound contrast agents may improve the
      treatment efficacy of HIFU for breast VX2 tumors in rabbits.

PMID- 23154001
TI  - Computed tomography coronary angiography and invasive coronary angiography
      demonstrate high correlation for area stenosis quantification in noncalcified and
      mixed plaques.
AB  - We compared the variance of area and diameter significant stenosis measurement
      between quantitative computed tomography coronary angiography (QCTA) and
      quantitative invasive coronary angiography (QCA). Fifty patients presenting 65
      significant coronary artery stenoses (>=70% area stenosis) in QCTA and QCA were
      included. Spearman's rank correlation revealed that area stenosis measurement by
      QCTA and QCA yields higher correlation than diameter stenosis and is highest for
      noncalcified and mixed lesions.

PMID- 23154002
TI  - Follow-up examination of 12 heart transplant recipients with cardiac CT.
AB  - OBJECTIVE: The aims of this study were to observe the changes of a transplanted
      heart with cardiac computed tomography (CT) and to evaluate the clinical
      application of the examination. METHODS: Cardiac CT was performed on 12 heart
      transplant recipients, of which 4 cases were also examined by echocardiography.
      Coronary arteries, the cardiac chamber, and the wall were shown with three
      dimensional imaging techniques, and their changes were analyzed and discussed.
      RESULTS: Twelve heart transplant recipients were successfully examined by CT. All
      transplanted hearts were found with good anastomosis at the great vessels and
      atria. Coronary allograft vasculopathy was found in 7 cases, of which 4 cases
      were found with ventricular dilation or ventricular septum thickening and 1 with
      tricuspid regurgitation. Ventricular dilation was found in other 3 cases, of
      which 1 was found with ventricular septum thickening and 1 with tricuspid
      regurgitation. No abnormality was found by cardiac CT in the rest 2 cases, which
      were found with mitral regurgitation by echocardiography. CONCLUSION: Cardiac CT
      can clearly and directly display the changes in the shape of a transplanted heart
      and coronary artery abnormalities. It will become an ideal noninvasive follow-up
      method for the heart transplant recipients.

PMID- 23154003
TI  - Primary lung cancers <1 cm found with MR screening appeared larger with half
      Fourier sequences than with three-dimensional acquisition techniques.
AB  - PURPOSE: The purpose was to objectively evaluate image quality characteristics of
      half-Fourier single-shot turbo spin-echo (HASTE) and three-dimensional volumetric
      interpolated breath-hold examination (3D-VIBE) for small (<1 cm) lung cancers
      found by magnetic resonance imaging (MRI) screening. METHODS: From 2000 to 2009,
      19,000 normal subjects were screened by MRI, and 15 cases were found to have lung
      cancers <1 cm. Those nodules were analyzed by image quality indices such as the
      signal to noise ratio, signal difference to noise ratio, percent contrast,
      percent contrast to noise ratio, and signal ratio of tumor to normal lung
      parenchyma. The area of the tumors measured by the two MR sequences and the
      computed tomography (CT) was compared. RESULTS: The lung cancers showed
      significantly higher percent contrast, percent contrast to noise, and the signal
      ratio of tumor to normal lung parenchyma by 3D-VIBE as compared to HASTE. Tumor
      area estimated by HASTE was significantly larger than that estimated by VIBE.
      There was no significant difference in the signal to noise ratio and signal
      difference to noise ratio between the two MR sequences. CONCLUSIONS: The 3D
      acquisition technique offers high contrast and contrast to noise ratios, while
      HASTE is associated with closer approximation of area estimation as compared to
      CT. Both sequences have similar signal to noise ratios and signal difference to
      noise ratios. The HASTE sequence is considered to be an essential part of imaging
      protocol in MR screening of lung especially for small nodules.

PMID- 23154004
TI  - Cardiovascular computed tomography angiography in newborns and infants with
      suspected congenital heart disease: retrospective evaluation of low-dose scan
      protocols.
AB  - Twelve infants (body weight, 3.59+/-1.36 kg) with congenital heart disease
      underwent a clinically indicated cardiovascular computed tomography angiography
      (CTA) study. Retrospectively, we investigated the feasibility and diagnostic
      capability of different non-electrocardiogram-triggered CTA protocols and
      assessed radiation doses. Scans were performed on a 256-multislice CT (MSCT)
      scanner with the vendor-preset helical protocol at 120 kV for babies, with axial
      single-shoot scans at 120 kV and 80 kV. The 80-kV protocol led to significantly
      reduced mean effective doses of 0.29+/-0.08 mSv (P=.017) and renders diagnostic
      image quality. All major cardiovascular defects were detected on MSCT, and all
      images were of diagnostic quality.

PMID- 23154005
TI  - Effectiveness of a breath-hold monitoring system in improving the reproducibility
      of different breath-hold positions in multiphasic CT imaging.
AB  - This study tests whether the utilization of an electronic breath-hold monitoring
      device improves breath-hold reproducibility during computed tomographic (CT)
      scanning. Two cohorts of 40 patients underwent dual-phase abdominal CT scans,
      either with a breath-hold monitoring device or with the standard breath-holding
      technique. Two blinded readers measured the differences in diaphragmatic position
      between phases. There was no statistical difference in diaphragmatic position
      (P=.14) between the monitored (8.5+/-11.5 mm) and control (5.6+/-5.2 mm) cohorts.
      Ten percent of patients from the monitored cohort had greater than 20 mm of
      deviation, versus 0%-2.5% for the control cohort. Reproduction of breath-holding
      position remains challenging, even with a monitoring system.

PMID- 23154006
TI  - Evaluation of normal appendix vermiformis in adults with multidetector computed
      tomography.
AB  - To determine the utility of different contrast enhancement phases (unenhanced,
      arterial, and venous), slice thicknesses (0.5, 3, and 5 mm), and planes (axial
      and coronal) in the evaluation of appendix vermiformis (AV) on multidetector
      computed tomography (MDCT), CT examinations of 600 patients were obtained. No
      significant difference was found between the different imaging planes, slice
      thicknesses, and contrast enhancement phases in terms of detection rates of AV.
      The mean diameter of AV in the axial plane (5.93+/-0.06 mm) was significantly
      lower than that in the coronal plane (6.18+/-0.06 mm). Evaluation of AV on MDCT
      is enhanced by combined interpretation on axial and coronal planes.

PMID- 23154007
TI  - Imaging late complications of cholecystectomy.
AB  - OBJECTIVE: To review the imaging findings in late complications of
      cholecystectomy. CONCLUSIONS: Late postcholecystectomy complications include
      papillary stenosis, choledocholithiasis, biliary stricture, remnant gallbladder,
      and dropped gallstones. Such complications can cause substantial morbidity, and
      knowledge of the imaging appearances can facilitate expeditious diagnosis and
      treatment.

PMID- 23154008
TI  - The relationship between ureteral stone characteristics and secondary signs in
      renal colic.
AB  - PURPOSE: To assess correlations between stone size/location and severity of
      secondary signs for ureteral obstruction. METHODS: Unenhanced multi-detector
      computed tomography examinations of 150 patients with acute renal colic were
      reviewed. Stone size, location in the ureter, kidney size and Hounsfield unit
      values, perinephric edema, and degree of hydronephrosis were assessed. RESULTS:
      Pale kidney sign was detected in 36%. Hydronephrosis was mild in 63% and severe
      in 21%; severe hydronephrosis was associated with larger stones. Mid-ureter and
      ureteropelvic junction stones were more likely to cause hydronephrosis.
      Perinephric edema (56%) was not correlated with stone size/location. CONCLUSION:
      Only severe hydronephrosis was significantly associated with larger stone size.

PMID- 23154010
TI  - Cancer in pregnancy: cross-sectional oncologic imaging utilization at a tertiary
      care center with an algorithmic approach to imaging.
AB  - PURPOSE: To review utilization of imaging in pregnant patients with malignancies
      and define an imaging algorithm in this patient population. METHODS: Pregnant
      patients with concurrent diagnoses of malignancy from January 2002 to January
      2011 were identified using an institutional electronic medical record system.
      Patients with history of malignancy concurrent with pregnancy who had documented
      cross-sectional imaging studies were included. Clinical charts were reviewed, and
      patient demographics, diagnoses, indication for imaging, imaging findings, and
      oncologic stage were recorded. Descriptive statistics were performed. RESULTS:
      Thirty-eight women were identified with malignancy concurrent with pregnancy.
      Twenty-seven patients had cross-sectional imaging studies during their pregnancy.
      There were 20 new diagnoses of malignancy and 7 with recurrent tumor. The most
      common new malignancies were lymphoma (5/27, 19%) and breast cancer (4/27, 15%).
      Two thirds (18/27, 66%) of the patients underwent at least one imaging study
      associated with ionizing radiation. CT imaging was utilized in 13 (48%) of 27
      patients and MRI was used in 14 (52%) of 27 patients. Fifteen (75%) of the 20
      patients with new diagnoses underwent oncologic staging with imaging that meets
      the standard of care based on National Comprehensive Cancer Network guidelines.
      An imaging algorithm was created as a guideline for the most common malignancies
      in pregnancy. CONCLUSIONS: Cross-sectional oncologic imaging in the pregnant
      patient involves a variety of imaging modalities including those with ionizing
      radiation. This imaging largely follows standard of care for the nonpregnant
      patient and is tailored to specific patient complaints. A generalized algorithm
      is offered here for imaging pregnant oncology patients.

PMID- 23154009
TI  - A comparison of pyelography and various reconstructions of multidetector helical
      computed tomography urography images for diagnosing urinary obstruction.
AB  - Radiologists and urologists require practical and helpful image reconstructions
      for diagnosing urinary obstruction. We performed different types of imaging and
      reconstruction, then used a self-designed urinary obstruction-specific
      questionnaire to evaluate the diagnostic outcome of them. Our results suggested
      that two-dimensional (2D) axial computed tomography (CT) is clinically superior
      to retrograde pyelography or antegrade pyelography, and to other modes of image
      reconstruction that are often used for diagnosing urinary obstruction.

PMID- 23154011
TI  - Rotator cuff tears: association with acromion angulation on MRI.
AB  - OBJECTIVE: Using magnetic resonance imaging (MRI), evaluate the correlation of
      acromion angulation with thickening of the coracoacromial ligament (CAL) and
      narrowing of the subacromial space resulting in impingement upon the rotator cuff
      tendons. MATERIALS AND METHODS: Eighty-nine shoulder MRI studies performed on a
      3T scanner were retrospectively analyzed by two blinded independent reviewers.
      Measurements of the acromion angle (delta angle), CAL thickness and distance
      between the CAL and humeral head were obtained. The data were categorized into
      two groups, delta angle less that and greater than 7.5 degrees . The presence or
      absence of full thickness (FT) or near full thickness (NFT) rotator cuff tears
      was noted. RESULTS: In group 1, the acromion angle varied from -6.8 to 6.8
      degrees  (1.7+/-3.5 degrees ) with a CAL thickness of 0.91+/-0.20 mm and a
      subacromial distance of 6.47+/-0.88 mm. Group 2 acromion angle varied from 7.6
      degrees  to 46.8 degrees  (18.0 degrees +/-8.1 degrees ) with a CAL of 1.77+/
      0.51 mm and a subacromial distance of 4.52+/-0.82 mm. The difference in CAL
      thickness and subacromial distance were significantly different between the two
      groups (P<.001). In Group 1, 3 out of 51 patients had a FT or NFT tear of the
      rotator cuff compared to 20 out of 38 in Group 2 (P<.001). There was no
      significant interobserver variability. CONCLUSION: Steep acromion angulation is
      associated with CAL thickening and narrowing of the subacromial space. Patients
      with a steep acromion angle had a statistically increased incidence of rotator
      cuff tears.

PMID- 23154012
TI  - Imaging features of posterior limbus vertebrae.
AB  - Posterior limbus vertebra (PLV) is the retropulsion of the vertebral ring
      apophysis resulting from disc herniation through posterior ring physis. Large PLV
      can cause spinal stenosis, and small PLV can be mistaken as intraspinal disc
      herniation. Although the clinical presentations were similar, the surgery was
      quite different. We had experienced preoperative misdiagnosed cases and the
      surgery could not be finished. Therefore we analyzed the imaging features of PLV
      in 34 patients in order to prompt appropriate preoperative diagnosis and surgical
      planning.

PMID- 23154013
TI  - Complementary effect of H MRS in diagnosis of suprasellar tumors.
AB  - OBJECTIVE: Suprasellar tumors are considered exceptionally important in
      neurosurgical practice due to their proximity to vital portions of the brain.
      Predicting histology of these tumors is of prime importance in determining the
      surgical approach, prognosis, and probable postoperative complications. There are
      numerous cases where computed tomography and magnetic resonance imaging (MRI)
      fail to predict histology. We have studied the role of magnetic resonance
      spectroscopy (MRS) in the diagnosis of suprasellar tumors. METHODS: Twenty-three
      patients with primary nonfunctional suprasellar tumors and high-quality magnetic
      resonance spectra were studied. The most probable diagnosis (adenoma, meningioma,
      craniopharyngioma, or astrocytoma) was made by a neuroradiologist based on the
      MRI findings and then based on MRI plus MRS findings. Finally, the results were
      compared with the pathology report. RESULTS: The information provided by MRS led
      the radiologist to alter his prior diagnosis that was based on the MRI in four
      patients, and the final diagnoses were in accordance with the histopathology.
      Wrong diagnosis was made by MRI plus MRS in three patients. Test efficiency of
      MRI was 69.6%, and it was 87% for MRI plus MRS. However, the difference was not
      statistically significant (P value=.152). CONCLUSION: MRS may be useful in
      providing a more improved preoperative diagnosis of suprasellar tumors.

PMID- 23154014
TI  - Fatigue-induced changes in longitudinal relaxation time determined by magnetic
      resonance imaging.
AB  - Longitudinal relaxation time (T(1)) determined by 3.0-T magnetic resonance
      imaging of the tibialis anterior and extensor digitorum longus muscles increased
      gradually with muscle fatigue caused by three 120-s periods of repeated ankle
      dorsiflexion separated by 5-min rest periods. T(1) values decreased in the
      recovery period, although they remained higher than the preexercise values. T(1)
      values for the soleus muscle were unchanged throughout the experiment. Results
      suggest that muscle T(1) values increase with increasing muscle fatigue.

PMID- 23154015
TI  - Aberrant right common carotid and subclavian arteries causing tracheoesophageal
      compression combined with persistent left superior vena cava--case report.
AB  - Vascular rings are a rare group of congenital thoracic vascular anomalies which
      are characterized by abnormal vascular structures that completely or incompletely
      encircle the trachea, esophagus, or both. We report the case of a vascular ring
      formed around the trachea and esophagus by aberrant right subclavian artery and
      aberrant right common carotid artery, associated with persistent left superior
      vena cava, complete absence of azygos vein, and with multiple nonvascular
      abnormalities. Recurrent pulmonary infections were the only clinical
      manifestation of this complex vascular anomaly. Our report represents a so-far
      undescribed anatomic variation of the vascular ring that clinicians should be
      aware of.

PMID- 23154016
TI  - Relapsing suppurative neck abscess after chemocauterization of pyriform sinus
      fistula.
AB  - We report a case of relapsing suppurative neck abscess due to a pyriform sinus
      fistula ever treated by chemocauterization. Pyriform sinus fistula is rare, and
      chemocauterization is an alternative microinvasive procedure. This case indicates
      that the possibility of recurrence following management of chemocauterization
      exists even after a long time and that clinical radiological assessments are
      necessary.

PMID- 23154017
TI  - Diabetic mastopathy: a case report.
AB  - Diabetic mastopathy (DMP) is an uncommon collection of clinical, radiological,
      and histological features, classically described in premenopausal women with long
      term insulin-dependent diabetes mellitus. This entity can mimic breast carcinoma,
      but, in the appropriate clinical and imaging setting, the diagnosis can be made
      by core biopsy, avoiding unnecessary surgeries. We report the case of a 34-year
      old female, with a 12-year history of type 1 diabetes, who presented with
      bilateral breast lumps. Mammography, ultrasonography, and magnetic resonance
      imaging could not exclude the suspicion of malignancy, and a core biopsy was
      performed showing the typical histologic features of DMP. The literature is
      briefly reviewed.

PMID- 23154018
TI  - Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH)
      masquerading as metastatic carcinoma with multiple pulmonary deposits.
AB  - Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH) is a rare
      pulmonary disorder presenting with multiple pulmonary nodules in association with
      a typical mosaic perfusion pattern on computed tomography. In this case, the
      absence of mosaic perfusion led to an erroneous initial diagnosis of pulmonary
      metastases from an unknown primary malignancy. This illustrates the importance of
      considering differential diagnoses when presented with imaging findings
      compatible with pulmonary metastases from an unknown primary, and highlights the
      importance of histopathologic confirmation in such cases.

PMID- 23154019
TI  - Thymic cyst arising in the middle mediastinum posterior to the left atrium--a
      peculiar location.
AB  - While masses of thymic origin are commonly located within the anterior
      mediastinum, abnormal migration of thymic tissue during development can result in
      thymic lesions in other intrathoracic locations. Ectopic thymic lesions in the
      middle mediastinum are extremely rare. We present a case of a calcified thymic
      cyst located posterior to the left atrium entirely within the caudal aspect of
      the middle mediastinum, a location not previously reported.

PMID- 23154020
TI  - Ventricular tachycardia in a patient with double valve replacement and bilateral
      coronary artery fistulas.
AB  - A young patient presented with hemodynamic instability due to wide QRS
      tachycardia occurring about 10 years after double valve replacement. Bilateral
      coronary artery fistulas draining into the pulmonary artery were documented by
      invasive coronary angiography as well as by computed tomography imaging. A
      calcified scar of the posterolateral left ventricle was considered to be the
      origin of the clinical ventricular tachycardia. Although additional pathological
      findings are rare in young patients with valvular heart disease, diagnostic
      imaging of the heart is mandatory prior to cardiac surgery.

PMID- 23154021
TI  - Isolated unilateral absence of pulmonary artery mimicking chronic pulmonary
      embolism at chest X-ray: multidetector-row CT angiographic findings.
AB  - Unilateral absence of pulmonary artery (UAPA) is a rare congenital anomaly which
      can seldom be isolated (1:200,000) and incidentally discovered in adulthood. We
      describe the case of a 54-year-old male patient who was found to have isolated
      UAPA (IUAPA) during the clinical and radiological investigation of a single
      episode of hemoptysis. Although abnormal, chest X-ray findings differed
      considerably from those previously reported and the diagnosis was only achieved
      by multidetector-row computed tomography angiography and later confirmed by bed
      side echocardiography. Further clinical and instrumental investigation revealed
      systemic hypertension (158/95 mmHg) and bilateral mild hydronephrosis which both
      remitted after transurethral prostatic adenomyomectomy.

PMID- 23154022
TI  - Popliteal artery entrapment syndrome with thrombosed popliteal aneurysm:
      multidetector computed tomography angiography findings of a case.
AB  - Popliteal artery entrapment syndrome (PAES) is a rare congenital vascular
      pathology caused by the compression of the popliteal artery by adjacent muscle
      and tendinous structures. Popliteal artery aneurysm associated with this syndrome
      is extremely rare. A 45-year-old male suffering from pain at the right lower
      extremity during exercise was admitted to our hospital. Physical examination and
      Doppler imaging revealed a weak pulse at the posterior tibial artery and no pulse
      at dorsalis pedis and anterior tibial arteries. The patient was further evaluated
      with multidetector computed tomography angiography (MDCTA). MDCTA revealed PAES
      due to compression of the accessory fibers of the gastrocnemius muscle and
      related thrombosed popliteal aneurysm.

PMID- 23154023
TI  - Invasive thymoma with venous intraluminal extension: CT and MRI findings.
AB  - We herein report an unusual case of invasive thymoma with venous intraluminal
      extension. The thymoma extended into the superior vena cava, the left
      brachiocephalic vein, and the proximal portion of the left jugular and subclavian
      veins intraluminally. It was suggested that the tumor had a discrete
      intravascular growth via the thymic vein into the left brachiocephalic vein and
      extended into the proximal portion of the left jugular and subclavian veins in
      the opposite direction of the venous stream.

PMID- 23154024
TI  - Xanthogranulomatous prostatitis: a rare entity resembling prostate adenocarcinoma
      with magnetic resonance image picture.
AB  - Granulomatous prostatitis, characterized by chronic granulomatous inflammation in
      the prostate, is rare. Xanthogranulomatous prostatitis is an even rarer
      granulomatous inflammation. We present a 74-year-old man who presented with lower
      urinary tract symptoms and elevated prostate specific antigen. A transrectal
      ultrasonography-guided prostate biopsy was performed, and pathological results
      showed foamy macrophage and inflammatory cell infiltrates, which were a
      distinctive feature of xanthogranulomatous prostatitis. We also present the
      characteristics of magnetic resonance imaging in xanthogranulomatous prostatitis
      which has never been previously described.

PMID- 23154025
TI  - Acute ischemic cholecystitis after transarterial chemoembolization with drug
      eluting beads.
AB  - Transarterial chemoembolization (TACE) is a widely used treatment choice for
      hepatocellular cancer. DC Bead microspheres are a new embolic material for TACE
      that doxorubicin can be loaded to. The tumor response rate of this well-tolerated
      treatment was changed between 60% and 81.8%. We report a case of ischemic
      cholecystitis after TACE with drug-eluting beads (DEB) that required
      cholecystectomy. The possibility of cholecystitis is always remembered during
      TACE-DEB for tumors in segment IV and/or V. Although selective catheterization is
      related with a lower risk for ischemic cholecystitis, the anatomic and vascular
      variability in patients with malignancy may lead to some unexpected conditions.

PMID- 23154027
TI  - Ectopic intracaval liver.
AB  - Congenital abnormalities of the liver are rare with prior descriptions of lobar
      or segmental agenesis, Reidel's lobe, and ectopic hepatic lobes. Intrathoracic
      ectopic hepatic lobes have been reported in many instances; however, there is
      only one documented case of abnormally positioned liver tissue within the
      inferior vena cava (J Chapman-Fredricks, R Birusingh, M Ricci, M Rodriguez,
      Intracaval liver with cardiac extension. A new developmental anomaly? Fetal and
      Pediatric Pathology. 2010; 29:401-406). We report a second case of an ectopic
      intracaval liver defined as a mass in an adult who presented for abdominal pain
      and review the radiological findings.

PMID- 23154026
TI  - Heparin-induced thrombocytopenia (HIT) causing portosplenic, superior mesenteric,
      and splenic vein thrombosis resulting in splenic rupture and pulmonary emboli
      formation.
AB  - Heparin-induced thrombocytopenia (HIT) is a life-threatening complication of
      heparin administration. Of the few reported cases of HIT-associated intra
      abdominal thrombosis, none to our knowledge provide multidetector-row computed
      tomography (MDCT) imaging findings or emphasize its utility in diagnosis. We
      describe a case of HIT with MDCT images demonstrating extensive intra-abdominal
      thrombosis and end-organ complications including splenic rupture and pulmonary
      emboli. This case emphasizes the potential role of MDCT in the rapid detection of
      HIT-related thromboembolic complications in patients with nonspecific abdominal
      pain.

PMID- 23154028
TI  - An unusual Hodgkin's lymphoma case presenting with upper extremity multiple
      masses.
AB  - Almost always, Hodgkin's lymphoma presents with lymph node involvement. Primary
      extranodal lymphoma is rare and mostly has a type of non-Hodgkin's lymphoma. We
      present an unusual presentation of a Hodgkin's lymphoma in a 33-year-old man.
      There were numerous soft tissue masses localized in the subcutaneous tissue of
      the left arm along the neurovascular bundle and the ipsilateral axillary region.
      We found only one Hodgkin's lymphoma case that presented as an upper extremity
      mass reported in the literature. In cases where a great number of successively
      lined up soft tissue masses are detected on the extremity, lymphoma takes place
      among the differential diagnoses.

PMID- 23154029
TI  - Imaging findings of Nasu-Hakola disease: a case report.
AB  - Nasu-Hakola disease (NHD), also known as polycystic lipomembranous osteodysplasia
      and sclerosing leukoencephalopathy, is a rare and fatal hereditary disease with
      less than 200 cases reported in the literature [Madry H, Prudlo J, Grgic A,
      Freyschmidt J. Nasu-Hakola disease (PLOSL): report of five cases and review of
      the literature. Clin Orthop Relat Res 2007;454:262-269]. This progressive disease
      is characterized by multiple cystic bone lesions, complicated with pathologic
      fractures and progressive dementia. Here in this article we report the imaging
      findings including magnetic resonance imaging of a newly diagnosed NHD case, with
      emphasis on the awareness of the radiologist for prompt recognition of this rare
      entity.

PMID- 23154030
TI  - Giant intradural extramedullary spinal hydatid cyst--a rare presentation.
AB  - The hydatidosis, or echinococcosis, has a characteristic geographic distribution,
      occurring most frequently in sheep-raising regions in Mediterranean, Central
      Asian, and South American countries and in Australia. Spinal hydatidosis is very
      rare, and intradural location is a rarer category of spinal hydatidosis. We
      report a case of intradural extramedullary spinal hydatid cyst in a 9-year-old
      boy. On magnetic resonance imaging, an intradural extramedullary giant cystic
      lesion was seen mimicking an arachnoid cyst. However, endemic origin of the
      patient and positive serology helped to make the diagnosis of hydatid cyst, which
      was confirmed on postoperative histopathology.

PMID- 23154031
TI  - Inelastic and elastic mean free paths from FIB samples of metallic glasses.
AB  - We have used focused ion beam (FIB) milling and scanning electron microscopy
      (SEM) to prepare samples of known thickness for measurement of the electron
      scattering elastic and inelastic mean free paths (EMFP and IMFP respectively) of
      three metallic glasses, Cu(64.5)Zr(35.5), Zr(50)Cu(45)Al(5), and
      Al(87)Y(7)Fe(5)Cu. After measuring the EMFP and IMFP in a scanning transmission
      electron microscope, we used the FIB to coat the lamellae with carbon on the top
      and bottom surfaces, which eliminated secondary electron emission from those
      surfaces and made SEM measurements of their thickness more reliable. At 200 kV,
      we find IMFP/ EMFP values of 146+/-2/43+/-1, 163+/-1/41+/-1, and 149+/-1/85+/-1
      nm, respectively for the three glass compositions. Our results differ from
      available models for the IMFP by as much as 50%.

PMID- 23154032
TI  - Variable magnification dual lens electron holography for semiconductor junction
      profiling and strain mapping.
AB  - Dual lens operation for electron holography, which was developed previously (Wang
      et al., Ultramicroscopy 101 (2004) 63-72; US patent: 7,015,469 B2 (2006)), is re
      investigated for bright field (junction profiling) and dark field (strain
      mapping) electron holography using FEI instrumentation (i.e. F20 and Titan). It
      is found that dual lens operation provides a wide operational range for electron
      holography. In addition, the dark field image tilt increases at high objective
      lens current to include Si <004> diffraction spot. Under the condition of high
      spatial resolution (1 nm fringe spacing), a large field of view (450 nm), and
      high fringe contrast (26%) with dual lens operation, a junction map is obtained
      and strain maps of Si device on <220> and <004> diffraction are acquired. In this
      paper, a fringe quality number, N', which is number of fringe times fringe
      contrast, is proposed to estimate the quality of an electron hologram and
      mathematical reasoning for the N' number is provided.

PMID- 23154033
TI  - Quantifying the low-energy limit and spectral resolution in valence electron
      energy loss spectroscopy.
AB  - While the development of monochromators for scanning transmission electron
      microscopes (STEM) has improved our ability to resolve spectral features in the 0
      5 eV energy range of the electron energy loss spectrum, the overall benefits
      relative to unfiltered microscopes have been difficult to quantify. Simple curve
      fitting and reciprocal space models that extrapolate the expected behavior of the
      zero-loss peak are not enough to fully exploit the optimal spectral limit and can
      hinder the ease of interpreting the resulting spectra due to processing-induced
      artifacts. To address this issue, here we present a quantitative comparison of
      two processing methods for performing ZLP removal and for defining the low-energy
      spectral limit applied to three microscopes with different intrinsic emission and
      energy resolutions. Applying the processing techniques to spectroscopic data
      obtained from each instrument leads in each case to a marked improvement in the
      spectroscopic limit, regardless of the technique implemented or the microscope
      setup. The example application chosen to benchmark these processing techniques is
      the energy limit obtained from a silicon wedge sample as a function of thickness.
      Based on these results, we conclude on the possibility to resolve statistically
      significant spectral features to within a hundred meV of the native instrumental
      energy spread, opening up the future prospect of tracking phonon peaks as new and
      improved hardware becomes available.

PMID- 23154034
TI  - The tibial crest as a practical useful landmark in total knee arthroplasty.
AB  - BACKGROUND: The middle one-third of the tibial crest in the coronal plane and the
      fibula in the sagittal plane are known as landmarks for extramedullary guides in
      total knee arthroplasty (TKA). However, there are few foundational anatomic
      studies about them. We conducted this study to confirm whether these landmarks
      are reliable. METHODS: We evaluated 100 Japanese knees using 3D imaging software.
      We examined our data for correlations between the angle of deviation from the
      mechanical axis and patient-specific factors (i.e. hip-knee-ankle angle, tibial
      length, tibial bowing, and tibial torsion) to determine whether there are any
      individual factors affecting their reliability. RESULTS: The mean angles between
      each of the axes defined by the fibula and the tibial crest with the mechanical
      axis were 2.9 degrees +/-0.6 degrees  of valgus and 0.7 degrees +/-0.9 degrees 
      of varus in the coronal plane and 2.2 degrees +/-0.8 degrees  of posterior and
      3.6 degrees +/-1.0 degrees  of anterior inclination in the sagittal plane. The
      middle one-third of the tibial crest (TCL) was revealed as a useful landmark,
      especially in female patients, who possess TCLs that were within 3 degrees  of
      the tibial mechanical axis in the coronal plane. There were no patient-specific
      factors strongly affecting reliability of these landmarks. CONCLUSIONS: We can
      use these landmarks even if the patient has tibial bowing or severe varus
      deformity. Although not considering soft tissue thickness, our study demonstrated
      that the tibial crest in the coronal and sagittal planes could be useful
      guidelines in performing TKAs. LEVEL OF EVIDENCE: II.

PMID- 23154035
TI  - Report of ganglion cyst in the anterior cruciate ligament of a 6-year-old child.
AB  - BACKGROUND: Intra-articular ganglion cysts of the knee are extremely rare within
      the pediatric population. To our knowledge, only seven case reports have been
      published in the medical literature identifying pediatric patients with intra
      articular cysts of the anterior cruciate ligament (ACL). Intra-articular cysts of
      the knee are a rare cause of knee discomfort and mechanical symptoms such as
      locking of the knee. To our knowledge, up until now the youngest patient reported
      in the medical literature with an intra-articular ganglion cyst of the ACL was a
      7-year-old boy. CASE REPORT: We describe a 6-year-old boy who presented with a
      unilateral intra-articular ganglion cyst of the ACL in the right knee. In
      addition to the diagnostic work-up of radiographs and MRI, the cyst was
      successfully treated with arthroscopic resection and debridement to decompress
      the cyst. CLINICAL RELEVANCE: We provide a review of the proposed pathogenesis,
      diagnostic modalities, differential diagnosis, treatment options, and
      complications of treatment for intra-articular cysts of the ACL. LEVEL OF
      EVIDENCE: Level V, case report.

PMID- 23154036
TI  - Periprosthetic bone mineral density changes after unicondylar knee arthroplasty.
AB  - BACKGROUND: Unicompartmental knee arthroplasty (UKA) has received renewed
      interest in the last decade. UKA involves minor injury to soft tissues, limited
      removal of bone and delicate preservation of knee anatomy and geometry. In
      theory, UKA provides an opportunity to restore post-surgical knee kinematics to
      near normal. HYPOTHESIS: UKA leaves patellofemoral joint free to meet high
      mechanical forces with no stress-shielding and therefore might preserve bone
      mineral density (BMD). PATIENTS AND METHODS: We studied 21 patients with
      osteoarthritis (OA), who had received medial compartment UKA at Kuopio University
      Hospital between October 1997 and September 2000. BMD was measured by dual-energy
      X-ray absorptiometry (DEXA), at baseline (within a week after surgery) and at
      intervals until 7 years. RESULTS: DEXA results were reproducible. The highest
      rate of periprosthetic bone loss occurred during the first 3 months after UKA.
      The average loss in BMD was 4.4% (p = 0.039) in the femoral diaphysis and it
      ranged from 11.2% (p < 0.001) to 11.9% (p = 0.002) in the distal femoral
      metaphysis; however, BMD changes in these regions, from 2 years to 7 years, were
      nonsignificant. At the 1-year follow-up, the BMD of the medial tibial metaphysis
      had increased by 8.9% (p = 0.02), whereas those in the lateral tibial metaphysial
      (-2.4%) and diaphysial regions (-2.0%) did not change significantly.
      INTERPRETATIONS: UKA did not preserve periprosthetic BMD in the distal femoral
      metaphysis, whereas BMD changes in the tibial metaphysis were minor, consistent
      with a mechanical balance between the medial and lateral tibial compartments.
      LEVEL OF EVIDENCE 2B: Prospective case control study.

PMID- 23154037
TI  - Antioxidant and antigenotoxic effects of lycopene in obstructive jaundice.
AB  - BACKGROUND: Obstructive jaundice, a frequently observed condition caused by
      obstruction of the common bile duct or its flow and seen in many clinical
      situations, may end up with serious complications like sepsis, immune depression,
      coagulopathy, wound breakdown, gastrointestinal hemorrhage, and hepatic and renal
      failures. Intrahepatic accumulation of reactive oxygen species is thought to be
      an important cause for the possible mechanisms of the pathogenesis of cholestatic
      tissue injury from jaundice. Carotenoids have been well described that are able
      to scavenge reactive oxygen species. Lycopene, a carotenoid present in tomatoes,
      tomato products, and several fruits and vegetables, have been suggested to have
      antioxidant activity, so may play a role in certain diseases related to the
      oxidative stress. The aim of the present study was to determine the effects of
      lycopene on oxidative stress and DNA damage induced by experimental biliary
      obstruction in Wistar albino rats. MATERIALS AND METHODS: Daily doses of 100
      mg/kg lycopene were given to the bile duct-ligation (BDL) rats orally for 14
      days. DNA damage was evaluated by an alkaline comet assay. The levels of
      aspartate transferase, amino alanine transferase, gamma glutamyl transferase,
      alkaline phosphatase, and direct bilirubin were analyzed in plasma for the
      determination of liver functions. The levels of malondialdehyde, reduced
      glutathione, nitric oxide, catalase, superoxide dismutase, and glutathione S
      transferase were determined in the liver and kidney tissues. Pro-inflammatory
      cytokine tumor necrosis factor-alpha level was determined in the liver tissues.
      Histologic examinations of the liver and kidney tissues were also performed.
      RESULTS: According to this study, lycopene significantly recovered the parameters
      of liver functions in plasma, reduced malondialdehyde and nitric oxide levels,
      enhanced reduced glutathione levels, as well as enhancing all antioxidant enzyme
      activity in all tissues obtained from the BDL group. Moreover, the parameters of
      DNA damage in the liver and kidney tissue cells, whole blood cells, and
      lymphocytes were significantly lower in the lycopene-treated BDL group, compared
      with the BDL group. CONCLUSIONS: Lycopene significantly reduced the DNA damage,
      and markedly recovered the liver and kidney tissue injuries seen in rats with
      obstructive jaundice.

PMID- 23154038
TI  - Hepatic amyloidosis: morphologic spectrum of histopathological changes in AA and
      nonAA amyloidosis.
AB  - In hepatic amyloidosis (HA), the relationships between the pattern and extent of
      amyloid deposition, morphologic changes, associated diseases and clinical data
      have not yet been demonstrated. In this study, we sought the correlation between
      the above mentioned parameters in HA. Liver biopsies of 34 HA were
      retrospectively analyzed for the type, distribution, and intensity of amyloid
      deposition and associated morphologic changes. AA and nonAA types were classified
      on the basis of immunohistochemistry. Follow-up clinical and laboratory findings
      were reviewed. Twenty-three out of 34 patients (67.6%) had AA, and 11 out of 34
      patients (32.4%) had nonAA amyloidosis. The predominant localization pattern in
      AA amyloidosis was vascular (91.3%), and in nonAA amyloidosis it was mixed with
      other patterns (72.7%). We confirmed that nonAA amyloid involves the hepatic
      artery, as well as the portal and central vein, but deposition occurred more
      frequently in the sinusoidal areas. We detected a portal stromal pattern only in
      cases of nonAA amyloidosis with a mixed pattern of amyloid deposition. The
      pattern of amyloid deposition in liver differs between the AA and nonAA type
      amyloidosis. The distribution of amyloid within the liver is not a reliable
      method for distinguishing AA from nonAA amyloidosis. However, the histological
      pattern provides strong clues as to the etiology of the amyloid deposits, and
      could provide information on the clinical status and prognosis of these patients.

PMID- 23154039
TI  - A historical perspective on the development of the cytarabine (7days) and
      daunorubicin (3days) treatment regimen for acute myelogenous leukemia: 2013 the
      40th anniversary of 7+3.
AB  - This paper reviews the development of therapy for acute myelogenous leukemia that
      in 1973 led to the regimen of 7days of continuous intravenous arabinosylcytosine
      (cytarabine) and the first 3 concurrent days of intravenous daunorubicin, given
      the nickname "7+3." The state of leukemia treatment in the 1950s, 1960s and early
      1970s is reviewed, the discovery of the two drugs in question described, and the
      introduction of clinical trials to reach an optimal regimen for their use
      delineated. During the 1950s, following World War Two and after a period of civil
      reconstitution, a national effort, facilitated by the U.S. Congress and federal
      investments in the National Cancer Institute, was initiated to enhance cancer
      therapy in the United States. The development of mouse models of leukemia and
      advances in understanding the structure and function of DNA and RNA and the
      process of cell proliferation provided new targets for drug development and new
      concepts for their use. The year, 2013, marks the 40th year that this protocol,
      7+3, is the method of induction of remission for most patients with acute
      myelogenous leukemia. Its inadequacies also are made clear. Many patients with
      the disease die soon after diagnosis, and patients who have more unfavorable
      oncogenetic subtypes, intrinsically drug resistant cells, and greater intolerance
      to therapy make up the vast majority of the affected and few are cured. It is
      evident to all that new paradigms are needed if acute myelogenous leukemia is to
      be subdued in most patients with the disease.

PMID- 23154041
TI  - CHiC, a new tandem affinity tag for the protein purification toolbox.
AB  - In the present work we have constructed a new tandem affinity purification tag
      and used it to purify two different polypeptides, PcsB and ECL1 from
      Streptococcus pneumoniae. PcsB probably functions as a peptidoglycan hydrolase
      and is believed to be involved in splitting of the septum during cell division.
      ECL1 is the extracellular domain of the membrane spanning protein FtsX.
      Experimental evidence indicates that the ECL1 domain controls the activity of
      PcsB through direct interaction (Sham et al., 2011). The affinity tag consists of
      an N-terminal 6xHis-tag, a choline binding domain followed by a proteolytic site
      specific for the TEV (tobacco etch virus) endopeptidase. Based on the choline
      binding His-tag combination the new 16.5 kDa tag was named CHiC. CHiC-tagged PcsB
      and ECL1 were expressed in Escherichia coli and sequentially purified by
      employing diethylaminoethyl-cellulose affinity chromatography and Ni(2+)
      immobilized metal affinity chromatography. After TEV digestion, the CHiC-tag, TEV
      protease and undigested fusion protein were easily separated from the target
      protein in a single purification step. By using this method, 4-7 mg of
      recombinant PcsB and ECL1 were obtained from one liter of cell culture with a
      purity estimated to be at least 95%. In addition, we found that the tag has the
      potential to function as a solubilisation partner as it markedly increased the
      solubility of PcsB. In sum, the CHiC-tag is a versatile tool that allows
      purification of milligram quantities of highly purified recombinant protein in
      only one or two steps.

PMID- 23154040
TI  - Visual attentional engagement deficits in children with specific language
      impairment and their role in real-time language processing.
AB  - In order to become a proficient user of language, infants must detect temporal
      cues embedded within the noisy acoustic spectra of ongoing speech by efficient
      attentional engagement. According to the neuro-constructivist approach, a multi
      sensory dysfunction of attentional engagement - hampering the temporal sampling
      of stimuli - might be responsible for language deficits typically shown in
      children with Specific Language Impairment (SLI). In the present study, the
      efficiency of visual attentional engagement was investigated in 22 children with
      SLI and 22 typically developing (TD) children by measuring attentional masking
      (AM). AM refers to impaired identification of the first of two sequentially
      presented masked objects (O1 and O2) in which the O1-O2 interval was manipulated.
      Lexical and grammatical comprehension abilities were also tested in both groups.
      Children with SLI showed a sluggish engagement of temporal attention, and
      individual differences in AM accounted for a significant percentage of unique
      variance in grammatical performance. Our results suggest that an attentional
      engagement deficit - probably linked to a dysfunction of the right fronto
      parietal attentional network - might be a contributing factor in these children's
      language impairments. 

PMID- 23154042
TI  - A rapid flow cytometric method for distinguishing between febrile bacterial and
      viral infections.
AB  - Antibiotic resistance due to the inappropriate use of antimicrobials is one of
      the most critical public health problems worldwide. A major factor underlying the
      unnecessary use of antibiotics is the lack of rapid and accurate diagnostic
      tests. Therefore, we aimed to develop a novel rapid flow cytometric method for
      distinguishing between febrile bacterial and viral infections. In this
      prospective comparative study, quantitative flow cytometric analysis of
      FcgammaRII/CD32, CR1/CD35, MHC Class I receptor (MHCI), and C5aR/CD88 on human
      phagocytes was performed in 286 hospitalized febrile patients with suspected
      infection. After using microbiological and serological detection methods, or
      clinical diagnosis, 205 patients were identified with either bacterial (n=136) or
      viral (n=69) infection. Receptor data from patients were compared to those of 50
      healthy controls. We developed a flow cytometric marker of local and systemic
      bacterial infections designated "bacterial infection score (BIS)" incorporating
      the quantitative analysis of FcgammaRII/CD32, CR1/CD35, C5aR/CD88 and MHCI on
      neutrophils and/or monocytes, which displays 91% sensitivity and 92% specificity
      in distinguishing between microbiologically confirmed bacterial (n=77) and
      serologically confirmed viral infections (n=61) within 1h. The BIS method was
      effectively applied to distinguish between bacterial and viral (pandemic H1N1
      influenza) pneumonia cases with 96% sensitivity and 92% specificity. We propose
      that the rapid BIS test can assist physicians in deciding whether antibiotic
      treatment is necessary, thus reducing unnecessary antimicrobial use.

PMID- 23154043
TI  - The use of high-resolution melting analysis for rapid spa typing on methicillin
      resistant Staphylococcus aureus clinical isolates.
AB  - Methicillin-resistant Staphylococcus aureus (MRSA) has been endemic in Hong Kong
      for three decades. This study evaluated the practical use of high-resolution
      melting (HRM) real-time PCR analysis on MRSA staphylococcal Protein A (spa)
      typing on local MRSA isolates. Among 55 clinical MRSA isolates collected in 2011,
      12 different spa types were observed by the conventional PCR-sequencing method
      including the locally predominant spa type t1081 and two locally predominant
      community acquired MRSA spa types t019 and t437. By using the HRM method, it
      could differentiate all 12 spa genotypes by distinct melting curves and HRM
      difference plot analysis. These two methods demonstrated 100% concordance whereas
      the HRM method required only 3h of turnaround time and one-fifth of reagent cost
      compared to the conventional method. Our study confirmed that the cost effective
      and rapid HRM typing approach is practically useful for MRSA community
      transmission monitoring and nosocomial outbreak control in Hong Kong.

PMID- 23154044
TI  - Use of MALDI-TOF mass spectrometry for identification of bacteria that are
      difficult to culture.
AB  - Rapid and reliable detection and identification of bacterial species are
      necessary for diagnosis and efficient treatment. Until recently, bacterial
      identification in clinical laboratories has mainly relied on conventional
      phenotypic and gene sequencing identification techniques. The identification of
      anaerobic bacteria, fastidious and slow growing bacteria using conventional
      methods is time consuming, expensive and complicated. Many anaerobes grow poorly
      or are nonreactive in most diagnostic systems. Unambiguous diagnosis of active
      tuberculosis is a time-consuming process, requiring as long as 12 weeks for
      positive identification of the organism. This long time frame presents challenges
      for case identification. Early identification of pathogenic bacteria is very
      important for the disease control. Recently, bacteriologists have focused their
      attention on the use of mass spectrometry (MS) for bacterial identification,
      especially Matrix Assisted Laser Desorption Ionization Time-Of-Flight (MALDI
      TOF). Use of MALDI-TOF-MS is described in this review, with a special emphasis on
      the successful identification of groups of bacteria, which are difficult to
      culture. MALDI-TOF-MS is a powerful, rapid, precise, and cost-effective method
      for identification of intact bacteria, compared to conventional phenotypic
      techniques or molecular biology. Our review suggests that identification of
      anaerobes, fastidious bacteria and slow growing bacteria, has been improved by
      the arrival of MALDI-TOF-MS in clinical laboratories.

PMID- 23154045
TI  - Assessment of intestinal microbiota modulation ability of Bifidobacterium strains
      in in vitro fecal batch cultures from preterm neonates.
AB  - Microbial colonization of the infant gut is essential for the development of the
      intestine and the immune system. The intestinal microbiota of full-term breast
      fed infants is considered as the health standard for newborns. A culture medium
      containing formula milk was designed, which allowed a balanced growth of
      intestinal microorganisms and was used to perform fecal batch cultures from
      preterm babies. Sixteen Bifidobacterium strains and fructooligosaccharides (FOS)
      were tested for their ability to modulate in vitro the intestinal microbiota. The
      production of short chain fatty acids (SCFA) was measured by Gas Chromatography
      and the levels of some anaerobe (Bifidobacterium and Bacteroides groups) and
      facultative anaerobes (Enterobacteriaceae, Enterococcaceae, Weissella group, and
      Klebsiella pneumoniae) were determined by quantitative PCR. Results were referred
      to a fecal negative control culture without microorganisms or FOS added. Strains
      that in fecal cultures counteracted better the aberrancies previously found in
      feces of preterm babies, as compared with full-term breast-fed infants, were
      selected. The three Bifidobacterium bifidum strains tested in this work promoted
      the most suitable shifts in SCFA and in the ratio of variables facultative
      anaerobes to anaerobes. Two Bifidobacterium breve strains complied with the
      requirement for facultative anaerobes and anaerobes and one of them also promoted
      a suitable shift of SCFA. Bifidobacteria behaved similarly as FOS regarding the
      microbial profiles in fecal cultures but the production of lactic and acetic acid
      was much lower. B. breve and B. bifidum strains selected represent promising
      candidates for their assessment in more complex in vitro and in vivo models.

PMID- 23154046
TI  - Pulmonary cryptococcosis in non-AIDS patients.
AB  - OBJECTIVE: To investigate the clinical features, management, and prognosis of
      pulmonary cryptococcosis in non-acquired immunodeficiency syndrome (AIDS)
      patients. METHOD: 24 cases of pulmonary cryptococcosis with accurate pathological
      diagnosis were retrospectively studied. RESULTS: 15 male patients and nine female
      patients were diagnosed at the first affiliated hospital of Sun Yat-sen
      University from November 1999 to November 2011. The mean age at the time of
      diagnosis was 44.2+/-11.3 years (range: 24 to 65 years). Among these patients, 13
      had other comorbidities. 15 were symptomatic and the other nine were
      asymptomatic. The most common presenting symptoms were cough, chest tightness,
      expectoration, and fever. None had concurrent cryptococcal meningitis. The most
      frequent radiologic abnormalities on chest computed tomography (CT) scans were
      solitary or multiple pulmonary nodules, and masses or consolidations, and most
      lesions were located in the lower lobes. All patients had biopsies for the
      accurate diagnosis. Among the 24 patients, nine patients underwent surgical
      resections (eight had pneumonectomy via thoracotomy and one had a pneumonectomy
      via thoracoscopy). Five of the patients who underwent surgery also received
      antifungal drug therapy (fluconazole) for one to three months after the surgery.
      The other 15 only received antifungal drug therapy (fluconazole or voriconazole)
      for three to six months (five patients are still on therapy). The follow-up
      observation of 19 patients who had already finished their treatments lasted from
      two to 11 years, and there was no relapse, dissemination, or death in any of
      these patients. CONCLUSION: Non-AIDS patients with pulmonary cryptococcosis have
      a good prognosis with appropriate management.

PMID- 23154047
TI  - Detection of bla(OXA-23) in Acinetobacter spp. isolated from patients of a
      university hospital.
AB  - INTRODUCTION: Acinetobacter spp. have emerged as notorious pathogens involved in
      healthcare-associated infections. Carbapenems are important antimicrobial agents
      for treating infections due to multidrug resistant Acinetobacter spp. Different
      mechanisms may confer resistance to these drugs in the genus, particularly
      production of class D carbapenemases. OXA-23-like family has been pointed out as
      one of the predominant carbapenamases among Acinetobacter. The present work aimed
      to investigate the occurrence of OXA-23-like carbapenemases among Acinetobacter
      isolates recovered from patients of a university hospital in Niteroi, RJ, Brazil.
      METHODS: Antimicrobial susceptibility profiles were determined by disk-diffusion.
      Imipenem resistant isolates were submitted to Modified Hodge Test in order to
      screen for carbapenemase production, and later to polymerase chain reaction (PCR)
      to investigate the presence of bla(OXA-23). RESULTS: Imipenem and meropenem
      resistance rates were 71.4% and 69.7%, respectively. The Modified Hodge Test
      revealed carbapenemase production among 76 (89.4%) of the 85 imipenem resistant
      isolates analyzed; according to PCR results, 81 isolates (95.4%) carried the
      bla(OXA-23) gene. CONCLUSIONS: OXA-23-like enzymes may be an important mechanism
      of carbapenem resistance among isolates present in the hospital studied.

PMID- 23154048
TI  - [Dropped head syndrome: a case study in a geriatric patient].

PMID- 23154049
TI  - Dementia and out-of-pocket spending on health care services.
AB  - BACKGROUND: High levels of out-of-pocket (OOP) spending for health care may lead
      patients to forego needed services and medications as well as hamper their
      ability to pay for other essential goods. Because it leads to disability and the
      loss of independence, dementia may put patients and their families at risk for
      high OOP spending, especially for long-term care services. METHODS: We used data
      from the Aging, Demographics, and Memory Study, a nationally representative
      subsample (n = 743) of the Health and Retirement Study, to determine whether
      individuals with dementia had higher self-reported OOP spending compared with
      those with cognitive impairment without dementia and those with normal cognitive
      function. We also examined the relationship between dementia and utilization of
      dental care and prescription medications-two types of health care that are
      frequently paid for OOP. Multivariate and logistic regression models were used to
      adjust for the influence of potential confounders. RESULTS: After controlling for
      demographics and comorbidities, those with dementia had more than three times the
      yearly OOP spending compared with those with normal cognition ($8216 for those
      with dementia vs. $2570 for those with normal cognition, P < .01). Higher OOP
      spending for those with dementia was mainly driven by greater expenditures on
      nursing home care (P < .01). Dementia was not associated with the likelihood of
      visiting the dentist (P = .76) or foregoing prescription medications owing to
      cost (P = .34). CONCLUSIONS: Dementia is associated with high levels of OOP
      spending but not with the use of dental care or foregoing prescription
      medications, suggesting that excess OOP spending among those with dementia does
      not "crowd out" spending on these other health care services.

PMID- 23154050
TI  - Alzheimer's disease pathology does not mediate the association between depressive
      symptoms and subsequent cognitive decline.
AB  - BACKGROUND: Depressive symptoms in nondemented individuals appear to hasten the
      progression from mild cognitive impairment to clinical Alzheimer's disease (AD)
      and double the risk of incident AD. However, the mechanism(s) by which depression
      might affect this risk has not been well established. The purpose of this
      analysis was to test the hypothesis that AD pathology mediates depression's
      apparent effect on the risk of dementia conversion using longitudinally collected
      psychometric testing and autopsy data from the Honolulu-Asia Aging Study.
      METHODS: Latent factor variables representing AD, cortical Lewy body (CLB), and
      ischemic neuropathology were tested as potential mediators of the association
      between the Center for Epidemiological Studies depression scale (CES-D) score and
      the 10-year prospective rate of cognitive decline, adjusted for baseline
      cognition, age, education, total number of medications, and brain weight at
      autopsy. RESULTS: CES-D scores, neurofibrillary tangle counts, CLB counts, and
      ischemic lesions each made significant independent contributions to cognitive
      decline. However, CES-D scores were not significantly associated with any
      pathological variable; thus the pathological variables were not mediators of the
      effect of CES-D scores on cognitive decline. CONCLUSIONS: Subsyndromal depressive
      symptoms are significantly associated with subsequent cognitive decline. Although
      the effect is relatively modest, it is stronger than that of amyloid-related
      neuropathologies and independent of that of neurofibrillary tangles, cortical
      Lewy bodies, and ischemic lesions. Our results argue against the role of AD
      related neuropathology as a mediator of depression's effect on cognitive decline,
      but cannot rule out a significant mediation effect in a subset of cases, perhaps
      with more severe baseline depressive symptoms.

PMID- 23154051
TI  - The synaptic proteome in Alzheimer's disease.
AB  - BACKGROUND: Synaptic dysfunction occurs early in Alzheimer's disease (AD) and is
      recognized to be a primary pathological target for treatment. Synapse
      degeneration or dysfunction contributes to clinical signs of dementia through
      altered neuronal communication; the degree of synaptic loss correlates strongly
      with cognitive impairment. The molecular mechanisms underlying synaptic
      degeneration are still unclear, and identifying abnormally expressed synaptic
      proteins in AD brain will help to elucidate such mechanisms and to identify
      therapeutic targets that might slow AD progression. METHODS: Synaptosomal
      fractions from human autopsy brain tissue from subjects with AD (n = 6) and
      without AD (n = 6) were compared using two-dimensional differential in-gel
      electrophoresis. AD pathology is region specific; human subjects can be highly
      variable in age, medication, and other factors. To counter these factors, two
      vulnerable areas (the hippocampus and the temporal cortex) were compared with two
      relatively spared areas (the motor and occipital cortices) within each group.
      Proteins exhibiting significant changes in expression were identified (>=20%
      change, Newman-Keuls P value < .05) using either matrix-assisted laser desorption
      ionization time-of-flight or electrospray ionisation quadrupole-time of flight
      mass spectrometry. RESULTS: Twenty-six different synaptic proteins exhibited more
      than twofold differences in expression between AD and normal subjects. These
      proteins are involved in regulating different cellular functions, including
      energy metabolism, signal transduction, vesicle transport, structure, and
      antioxidant activity. CONCLUSION: Comparative proteome analysis uncovered markers
      of pathogenic mechanisms involved in synaptic dysfunction.

PMID- 23154052
TI  - Brain, networks, depression, and more.
AB  - Depression is a heterogeneous disorder with a highly variable course. Individual
      responses to treatment are inconsistent, and an established mechanism remains
      elusive. The classical hypothesis of depression posits that mood disorders are
      caused by a chemical imbalance in the brain that can be corrected with
      antidepressant drugs. However, recent evidence indicates that information
      processing dysfunction within neural networks might underlie depression, and
      antidepressant drugs induce plastic changes in neuronal connectivity that
      gradually lead to improvements in neuronal information processing and recovery.
      This review presents the major current approaches to understanding the biological
      mechanisms of major depression, with a focus on complex brain networks.

PMID- 23154053
TI  - ACCF 2012 expert consensus document on practical clinical considerations in the
      interpretation of troponin elevations: a report of the American College of
      Cardiology Foundation task force on Clinical Expert Consensus Documents.

PMID- 23154054
TI  - Psychological factors associated with indices of risky, reckless and cautious
      driving in a national sample of drivers in the Republic of Ireland.
AB  - This paper presents the results of a national survey of drivers in the Republic
      of Ireland that sought to examine psychological predictors of specific driving
      behaviours. 1638 respondents attending National Car Testing (NCT) centres
      nationwide completed a questionnaire battery that included personality,
      attitudinal, locus of control and social influence measures. The driving
      behaviours examined were drawn from a Driving Behaviour Scale (Iversen, 2004) and
      included Speeding and Rule Violation, Reckless Driving, Wearing of Seat Belts,
      Cautious Driving and Drink Driving. Cross-group comparisons suggested that males
      engaged in more risky and less cautious driving behaviours than females, and
      participants under the age of 25 were more risky and less cautious than those 25
      years or older. Statistically significant models of each driving outcome emerged.
      The best model fit was for speeding and rule violation, which was predicted by a
      model including positive attitudes towards speeding, greater normative influences
      of friends and higher perceived behavioural control, extraversion and driving
      anger. These findings offer important insights into the correlates of different
      driving behaviours and can help inform the work of road safety practitioners.

PMID- 23154055
TI  - Resistance training improves cardiac output, exercise capacity and tolerance to
      positive airway pressure in Fontan physiology.
AB  - BACKGROUND: Subjects with Fontan-type circulation have no sub-pulmonary ventricle
      and thus depend exquisitely on the respiratory bellows and peripheral muscle pump
      for cardiac filling. We hypothesised that resistance training to augment the
      peripheral muscle pump might improve cardiac filling, reduce inspiratory
      dependence of IVC return to the heart and thus improve exercise capacity and
      cardiac output on constant positive airway pressure (CPAP). METHODS: Eleven
      Fontan subjects (32+/-2 years, mean+/-SEM) had cardiac magnetic resonance imaging
      (MRI) and exercise testing (CPET); six underwent 20 weeks of high-intensity
      resistance training; others were non-exercising controls. After training, CPET
      was repeated. Four trainers had MRI with real-time flow measurement at rest,
      exercise and on CPAP in the trained state and following a 12-month detrain.
      RESULTS: In the trained state, muscle strength increased by 43% (p=0.002), as did
      total muscle mass (by 1.94 kg, p=0.003) and peak VO2 (by 183 ml/min, p=0.02).
      After detraining, calf muscle mass and peak workload had fallen significantly
      (p<0.03 for both) as did peak VO2 (2.72 vs. 2.18 l/min, p<0.001) and oxygen
      pulse, a surrogate for SV (16% lower, p=0.005). Furthermore after detraining, SV
      on MRI decreased at rest (by 11 ml, p=0.01) and during moderate-intensity
      exercise (by 16 ml, p=0.04); inspiratory-dependent IVC blood return during
      exercise was 40% higher (p=0.02). On CPAP, cardiac output was lower in the
      detrained state (101 vs. 77 ml/s, p=0.03). CONCLUSIONS: Resistance muscle
      training improves muscle mass, strength and is associated with improved cardiac
      filling, stroke volume, exercise capacity and cardiac output on CPAP, in adults
      with Fontan-type circulation.

PMID- 23154056
TI  - Cardioprotective molecules are enriched in beating cardiomyocytes derived from
      human embryonic stem cells.
AB  - BACKGROUND: Cardiomyocytes derived from human embryonic stem cells (hESC-CMs)
      have attracted attention because of their cardiac regenerative potential in vivo.
      Differentiated CMs can be distinguished into two different phenotypic
      populations: beating and non-beating CMs. A thorough understanding of the
      different molecular conditions of beating and non-beating CMs would provide
      valuable information for other potential applications and cell therapy. METHODS:
      In this study, we generated a comparative protein profiles using proteomic
      analysis and western blotting, to compare the specific protein expression
      patterns of beating and non-beating hESC-CMs. RESULTS: Abundantly 72 upregulated
      proteins are involved in different biological processes such as stimulus
      response, cellular catabolism and cell motility. Among these proteins, such as
      HSPs and other antioxidant molecules, are known to be proteins that potentially
      play an important role in cardioprotection through the enhancement of cell
      survival in hypoxic and ischemic conditions present in the injured heart.
      CONCLUSION: As a first step toward understanding the different molecular
      conditions of beating and non-beating hESC-CMs, we sought to study their
      differential expression patterns and discuss their relevance to in vivo
      functioning in cardiac injury repair. Thus, the results of this study could
      provide further evidence supporting a cardiac regenerative approach using an
      optimized cell source derived from hESCs.

PMID- 23154057
TI  - Interaction between hypertension and HSP70 variants increase the risk of cerebral
      ischemia in Chinese Han population: an association study.
AB  - Cerebral infarction has become one of the leading diseases and a major mortality
      factor around the world. Atherosclerosis is recognized as one of the important
      causes of ischemic stroke. Recently, accumulating evidences have indicated that
      the anti-inflammatory and anti-apoptotic functions of the HSP70 family play an
      important role in cerebral ischemia. However, the association between HSP70 SNPs
      and ischemic stroke was also not well established. We chose 101 cases of cerebral
      ischemia and 100 healthy people from the Chinese Han population as our study
      subjects, and PCR-RFLP was employed to analyze HSP70 polymorphisms: HSP70
      1+190G/C, HSP70-2+1267A/G and HSP70-hom+2437T/C. There were no significant
      differences in +1267A/G allele or genotype frequencies between patients with
      stroke and healthy controls. However, genotypes of +190CG and +2437TT were
      differentially distributed between the patients and controls. A significant
      difference of T allele distribution in the HSP70-hom+2437T/C site was observed.
      Logistic regression analysis indicated that genotypes of +190CG, +2437TT and T
      allele in HSP70-hom were risk factors of ischemic stroke. Moreover, the study has
      formulated that the interactions between hypertension and +190CG or +2437TT may
      increase the risks of ischemic stroke. The results from this study have suggested
      a clinical indicator for assessing the possibilities of cerebral stroke, and
      supply basis to clinicians to give precaution to people who are at risk of
      stroke.

PMID- 23154058
TI  - Epilepsy in adult X-linked adrenoleucodystrophy due to the deletion c.1415
      1416delAG in exon 5 of the ABCD1-gene.
AB  - Seizures in cerebral X-linked adrenoleucodystrophy (X-ALD) more frequently occur
      in the early-onset compared to the late-onset form. Here we describe an adult in
      whom X-ALD deteriorated after head trauma and who developed epilepsy with
      progression of X-ALD. In a 50 year-old Caucasian male, cerebral X-ALD was
      diagnosed upon progressive gait disturbance, intellectual decline, elevated very
      long chain fatty acids in the serum or leucocytes, cerebral MRI, showing
      extensive, symmetric, homogenous demyelination in the parieto-occipital areas,
      the splenium corporis callosum, the thalamus, the crura cerebri, the brain stem,
      and the pedunculi cerebelli, and the deletion c.1415-1416delAG in the ABCD1-gene.
      After a head trauma the phenotype deteriorated to mutism, dysphagia, and severe
      spastic quadruparesis. At an age of 50 years the patient experienced his first,
      self-limiting, tonic-clonic seizure during an infection, which is why valproic
      acid was started. Recurrence of seizures after discharge required repeated
      adaptation of the valproic acid-dosage. Adult X-ALD may be associated with late
      onset seizures, which respond favourably to valproic acid. Since any type of
      seizure episode in adult-onset cerebral X-ALD is usually followed by neurological
      decline, prophylactic treatment with antiepileptic drugs should be considered not
      only in early-onset but also in adult-onset epilepsy in X-ALD.

PMID- 23154059
TI  - Localization of germline marker vasa homolog RNA to a single blastomere at early
      cleavage stages in the oriental river prawn Macrobrachium nipponense: evidence
      for germ cell specification by preformation.
AB  - Germ cells are specified by the inheritance of maternal germline determinants
      (preformation mode) or inductive signals from somatic cells (epigenesis mode)
      during embryogenesis. However, the germline specification in decapod crustaceans
      is unclear so far. Using vasa homolog (MnVasa) as a germ cell marker, here we
      probed the early events of germline specification in the oriental river prawn
      Macrobrachium nipponense. Quantitative RT-PCR analysis of unfertilized eggs and
      embryos demonstrated that the prawn MnVasa mRNA is a maternal factor. Whole-mount
      in situ hybridization further indicated that MnVasa transcripts are maternally
      supplied to only one blastomere at the very early cleavage stages. As cleavage
      proceeds, the MnVasa-positive blastomere undergoes proliferation and increases in
      number. During gastrulation, the MnVasa-positive cells are found to be around a
      blastopore and could migrate into an embryo through the blastopore. At the zoea
      stage, clusters of the MnVasa-positive cells distribute not only in the gonad
      rudiment in the cephalothorax but also at an extragonadic site, dorsal to the
      posterior hindgut in the abdomen, suggesting that MnVasa-positive cells could
      migrate anteriorly to the genital rudiment through the hindgut. Based on the
      dynamic localization and number of MnVasa-positive cells during embryogenesis, we
      concluded that the MnVasa-positive cells are primordial germ cells (PGC) or
      founder cells of PGC that are separated from soma at the early cleavage stage.
      MnVasa mRNA might have a key function in the specification of the prawn germline
      cells as a maternal determinant. These results provide the first evidence that
      the germline specification in decapod crustaceans follows a preformation mode.

PMID- 23154060
TI  - Molecular characterization and expression analysis of ubiquitin-activating enzyme
      E1 gene in Citrus reticulata.
AB  - Ubiquitin-activating enzyme E1 (UBE1) catalyzes the first step in the
      ubiquitination reaction, which targets a protein for degradation via a proteasome
      pathway. UBE1 plays an important role in metabolic processes. In this study, full
      length cDNA and DNA sequences of UBE1 gene, designated CrUBE1, were obtained from
      'Wuzishatangju' (self-incompatible, SI) and 'Shatangju' (self-compatible, SC)
      mandarins. 5 amino acids and 8 bases were different in cDNA and DNA sequences of
      CrUBE1 between 'Wuzishatangju' and 'Shatangju', respectively. Southern blot
      analysis showed that there existed only one copy of the CrUBE1 gene in genome of
      'Wuzishatangju' and 'Shatangju'. The temporal and spatial expression
      characteristics of the CrUBE1 gene were investigated using semi-quantitative RT
      PCR (SqPCR) and quantitative real-time PCR (qPCR). The expression level of the
      CrUBE1 gene in anthers of 'Shatangju' was approximately 10-fold higher than in
      anthers of 'Wuzishatangju'. The highest expression level of CrUBE1 was detected
      in pistils at 7days after self-pollination of 'Wuzishatangju', which was
      approximately 5-fold higher than at 0 h. To obtain CrUBE1 protein, the full
      length cDNA of CrUBE1 genes from 'Wuzishatangju' and 'Shatangju' were
      successfully expressed in Pichia pastoris. Pollen germination frequency of
      'Wuzishatangju' was significantly inhibited with increasing of CrUBE1 protein
      concentrations from 'Wuzishatangju'.

PMID- 23154061
TI  - Molecular characterization and genetic variability at kappa-casein gene (CSN3) in
      camels.
AB  - kappa-casein is a glycosilated protein belonging to a family of phosphoproteins
      (alphas1, beta, alphas2, kappa) that represent the major protein component in
      mammalian milk. kappa-casein plays an essential role in the casein micelle
      stabilization, determining the size and the specific function. In the present
      paper, we report for the first time the characterization of the nucleotide
      sequence of the whole kappa-casein-encoding gene (CSN3) plus 1045 nucleotides at
      the 5' flanking region in Camelus dromedarius. The promoter region and the
      complete cDNA were also provided for the first time in Camelus bactrianus. The
      gene is spread over 9.3kb and consists of 5 exons varying in length from 33bp
      (exon 3) to 494bp (exon 4), and 4 introns from 1200bp (intron 3) to 2928bp
      (intron 2). Highly conserved sequences, located in the 5' flanking region, have
      been found. The regulatory regions of camels seems to be more related to equids
      than to other compared species. 17 polymorphic sites have been detected, one of
      these (g.1029T>C) is responsible for the creation of a new putative consensus
      sequence for the transcription factor HNF-1. In general, these SNPs are the first
      reported in camels for casein loci. Finally, seven interspersed repeated elements
      were also identified at intronic level.

PMID- 23154062
TI  - Functional and evolutionary analysis of DXL1, a non-essential gene encoding a 1
      deoxy-D-xylulose 5-phosphate synthase like protein in Arabidopsis thaliana.
AB  - The synthesis of 1-deoxy-D-xylulose 5-phosphate (DXP), catalyzed by the enzyme
      DXP synthase (DXS), represents a key regulatory step of the 2-C-methyl-D
      erythritol 4-phosphate (MEP) pathway for isoprenoid biosynthesis. In plants DXS
      is encoded by small multigene families that can be classified into, at least,
      three specialized subfamilies. Arabidopsis thaliana contains three genes encoding
      proteins with similarity to DXS, including the well-known DXS1/CLA1 gene, which
      clusters within subfamily I. The remaining proteins, initially named DXS2 and
      DXS3, have not yet been characterized. Here we report the expression and
      functional analysis of A. thaliana DXS2. Unexpectedly, the expression of DXS2
      failed to rescue Escherichia coli and A. thaliana mutants defective in DXS
      activity. Coherently, we found that DXS activity was negligible in vitro, being
      renamed as DXL1 following recent nomenclature recommendation. DXL1 is targeted to
      plastids as DXS1, but shows a distinct expression pattern. The phenotypic
      analysis of a DXL1 defective mutant revealed that the function of the encoded
      protein is not essential for growth and development. Evolutionary analyses
      indicated that DXL1 emerged from DXS1 through a recent duplication apparently
      specific of the Brassicaceae lineage. Divergent selective constraints would have
      affected a significant fraction of sites after diversification of the paralogues.
      Furthermore, amino acids subjected to divergent selection and likely critical for
      functional divergence through the acquisition of a novel, although not yet known,
      biochemical function, were identified. Our results provide with the first
      evidences of functional specialization at both the regulatory and biochemical
      level within the plant DXS family.

PMID- 23154063
TI  - Akt1 as a putative regulator of Hox genes.
AB  - In mammals, precise spatiotemporal expressions of Hox genes control the main body
      axis during embryogenesis. However, the mechanism by which Hox genes are
      regulated is poorly understood. To discover the putative regulator of Hox genes,
      in silico analyses were performed using GEO profiles, and Akt1 emerged as a
      candidate regulator of Hox genes in E13.5 MEFs. The results of the RT-PCR showed
      that 5' Hoxc genes, including ncRNA were upregulated in Akt1 null MEF. Combined
      bisulfite restriction analysis (COBRA) and bisulfite sequencing showed that the
      CpG island of a 5' Hoxc gene was hypomethylated in Akt1 null cells. These results
      indicate that Hox expression could be controlled by the function of Akt1 through
      epigenetic modification such as DNA methylation.

PMID- 23154064
TI  - In utero and childhood polybrominated diphenyl ether (PBDE) exposures and
      neurodevelopment in the CHAMACOS study.
AB  - BACKGROUND: California children's exposures to polybrominated diphenyl ether
      flame retardants (PBDEs) are among the highest worldwide. PBDEs are known
      endocrine disruptors and neurotoxicants in animals. OBJECTIVE: Here we
      investigate the relation of in utero and child PBDE exposure to neurobehavioral
      development among participants in CHAMACOS (Center for the Health Assessment of
      Mothers and Children of Salinas), a California birth cohort. METHODS: We measured
      PBDEs in maternal prenatal and child serum samples and examined the association
      of PBDE concentrations with children's attention, motor functioning, and
      cognition at 5 (n = 310) and 7 years of age (n = 323). RESULTS: Maternal prenatal
      PBDE concentrations were associated with impaired attention as measured by a
      continuous performance task at 5 years and maternal report at 5 and 7 years of
      age, with poorer fine motor coordination-particularly in the nondominant-at both
      age points, and with decrements in Verbal and Full-Scale IQ at 7 years. PBDE
      concentrations in children 7 years of age were significantly or marginally
      associated with concurrent teacher reports of attention problems and decrements
      in Processing Speed, Perceptual Reasoning, Verbal Comprehension, and Full-Scale
      IQ. These associations were not altered by adjustment for birth weight,
      gestational age, or maternal thyroid hormone levels. CONCLUSIONS: Both prenatal
      and childhood PBDE exposures were associated with poorer attention, fine motor
      coordination, and cognition in the CHAMACOS cohort of school-age children. This
      study, the largest to date, contributes to growing evidence suggesting that PBDEs
      have adverse impacts on child neurobehavioral development.

PMID- 23154066
TI  - Neonatal outcome and congenital malformations in children born after ICSI with
      testicular or epididymal sperm: a controlled national cohort study.
AB  - STUDY QUESTION: Does neonatal outcome including congenital malformations in
      children born after ICSI with epididymal and testicular sperm [testicular sperm
      extraction (TESE)/percutaneous epididymal sperm aspiration (PESA)/testicular
      sperm aspiration (TESA) (TPT)] differ from neonatal outcome in children born
      after ICSI with ejaculated sperm, IVF and natural conception (NC)? SUMMARY
      ANSWER: Children born after TPT have similar neonatal outcome, including total
      malformation rates, as have children born after ICSI and IVF with ejaculated
      sperm. Testing for variance over the four groups may indicate smaller differences
      in specific malformation rates with TPT as the highest risk group. WHAT IS KNOWN
      ALREADY: Regarding neonatal outcome as well as congenital malformations in
      children born after TPT, studies are few, with limited sample size, heterogeneous
      and often performed without relevant control groups. STUDY DESIGN, SIZE,
      DURATION: Population-based cohort study including all Danish children born after
      TPT and fresh embryo transfer in Denmark from 1995 to 2009. Children born after
      transfer of frozen-thawed embryos were excluded. Control groups of children
      conceived by ICSI with ejaculated sperm, IVF and NC were identified by cross
      linkage of the Danish IVF Register, Medical Birth Register (MBR) and National
      Hospital Discharge Register (HDR). PARTICIPANTS/MATERIALS, SETTING: The study
      group consisted of 466 children born after TPT, while the control groups
      consisted of 8967 (ICSI with ejaculated sperm), 17 592 (IVF) and 63 854 (NC)
      children. Neonatal outcomes and congenital malformations were analysed for
      singletons and twins separately. Risk estimates for low birthweight (LBW, <2500
      g) and preterm birth (PTB, <37 gestational weeks) were adjusted for maternal age,
      parity, child gender and year of childbirth. The study group was identified from
      the Danish national database on children born after TPT. Control groups were
      obtained from the IVF register and the MBR. All information included in the study
      was retrieved from the national registers. MAIN RESULTS AND THE ROLE OF CHANCE:
      Considering singletons and twins as one group, the sex ratio (?/?) was
      significantly lower for children born after TPT (0.89) compared with conventional
      IVF (1.11; P = 0.017) but did not differ significantly when compared with ICSI
      with ejaculated sperm (0.94) and NC (1.05). The mean birthweight (BW) for
      singletons did not differ significantly between groups when including only first
      born children. The mean gestational age (GA) in the TPT singletons (279 +/- 12
      days) was significantly higher compared with IVF (276 +/- 18 days; P = 0.02), but
      similar to ICSI with ejaculated sperm and NC singletons when including only first
      born children (277 +/- 16 days and 279 +/- 14 days, respectively). Rate of
      stillbirths, perinatal and neonatal mortality in the group of TPT singletons did
      not differ significantly from any of the control groups. Comparable results were
      found for the TPT twin group, except for perinatal mortality, which was
      significantly lower in the TPT group compared with naturally conceived twins. The
      adjusted risk of LBW was significantly higher for TPT versus NC singletons
      [adjusted odds ratio (AOR) = 0.67 (0.48-0.93)]; however AOR for PTB was similar
      in the two groups. Regarding twins, similar adjusted risks were observed for PTB
      and LBW between the TPT and all three control groups. Significantly more
      Caesarean sections were performed after IVF (27.3% for singletons) and ICSI
      (25.1% for singletons) with ejaculated sperm compared with the TPT group (16.4%
      for singletons). The total rate of congenital malformations in the TPT group was
      7.7% and did not differ significantly from any of the control groups. However,
      singleton TPT boys showed an increased rate of cardiac malformations (3.6%)
      compared with singleton boys after IVF (1.4%; P = 0.04) and NC (1.1%; P = 0.02).
      Considering the level of male infertility as a continuum over the four groups,
      tests for variance in the rate of cardiac malformations in singleton boys, and
      undescended testicles for singleton as well as twin boys were each significantly
      increased from NC to IVF to ICSI to TPT (P < 0.001). The rate of hypospadias
      showed the same pattern, but the TPT group did not differ significantly compared
      with the control groups. LIMITATIONS, REASONS FOR CAUTION: One of the limitations
      is that the TPT group could not be classified according to testicular or
      epididymal sperm, as these data were not available in the IVF register. Another
      limitation is that registry-based studies are encumbered with the risk of
      reporting or coding errors or missing data due to insufficient coding. However,
      the quality of data on congenital malformations in HDR has, in other studies,
      been validated and found acceptable for epidemiological research, and
      furthermore, recordings on study and control groups are performed similarly.
      WIDER IMPLICATIONS OF THE FINDINGS: Accumulating data show that TPT treatment is
      equally safe as conventional ICSI and IVF treatment and as NC with regard to
      neonatal outcome including congenital malformation. STUDY FUNDING/POTENTIAL
      COMPETING INTERESTS: This study is supported by Laboratory of Reproductive
      Biology, Scientific Unit, Horsens Hospital. No competing interests declared.

PMID- 23154067
TI  - Age at menopause and its influencing factors in a cohort of survivors of
      childhood cancer: earlier but rarely premature.
AB  - STUDY QUESTION: Is the age at menopause in a cohort of childhood cancer survivors
      earlier and what are the risk factors associated with earlier age at menopause?
      SUMMARY ANSWER: Menopause occurred at a median age of 44 years in this cohort
      which is earlier than in the general population, but premature menopause was
      uncommon. Main risk factors for non-surgical menopause were exposure to and dose
      of alkylating agents, especially during adolescence, radiation dose to the
      ovaries and oophorectomy. WHAT IS KNOWN ALREADY: While survivors of childhood
      cancer are known to be at increased risk for developing premature menopause, data
      on its risk factors are limited. STUDY DESIGN: A cohort study of 1109 still
      living female survivors of childhood solid cancer treated between 1945 and 1985,
      of whom 863 (78%) returned a follow-up questionnaire. Of them, 157 were excluded.
      PARTICIPANTS AND METHODS: Seven hundred and six women, among whom 32% have
      attained 40 years of age, were included in this study. A Cox regression model was
      used to determine risk factors influencing the age at menopause. MAIN RESULTS:
      Ninety seven women have reached menopause at a median age of 44 years. Menopause
      has been surgically induced in 36% of women. In multivariate analysis, risk
      factors for non-surgical menopause included exposure to alkylating agents,
      increasing radiation dose to the ovaries, procarbazine dose, cyclophosphamide
      dose and unilateral oophorectomy. The highest risk ratio for non-surgical
      menopause was observed for women treated after the onset of puberty with
      alkylating agents, either alone (RR = 9, 95% CI: 2.7-28, P = 0.0003) or
      associated with even a low dose of radiation to the ovaries (RR = 29, 95% CI: 8
      108, P < 0.0001). Exposure to unilateral oophorectomy is associated with a 7-year
      earlier age at menopause. By the age of 40, only 2.1% had non-surgical premature
      menopause and its main risk factors were age at diagnosis, cyclophosphamide dose,
      exposure to melphalan and radiation dose to the ovaries. LIMITATIONS: The
      information on menopause was based on self-reported data without confirmation by
      FSH levels. Participants to this study have been treated for cancer from 1945 to
      1985 and one can expect an increase in premature menopause incidence with more
      recent protocols using high-dose alkylating agents. WIDER IMPLICATIONS OF THE
      FINDINGS: This study provides data on risk factors for a reduced fertility window
      in order to inform survivors at risk and help oncologists to design new
      therapeutic protocols avoiding this risk. This study does not confirm the high
      rate of premature menopause reported by the Childhood Cancer Survivor Study, but
      this population differs from theirs (no leukemia and a lower percentage of
      lymphoma).

PMID- 23154068
TI  - The association of CGG repeats in the FMR1 gene and timing of natural menopause.
AB  - STUDY QUESTION: Is there an association between the number of CGG repeats in the
      FMR1 gene in the normal and intermediate range and age at natural menopause?
      SUMMARY ANSWER: The number of CGG repeats in the normal and intermediate range in
      the FMR1 gene was not associated with age at natural menopause. WHAT IS KNOWN
      ALREADY: Excessive triple CGG repeats in the FMR1 gene have been widely
      associated with primary ovarian insufficiency. Recently, the number of CGG
      repeats in the normal and intermediate range (up to 55 repeats) was found to be
      associated with serum levels of anti-Mullerian hormone and follicle-stimulating
      hormone, as markers for ovarian ageing. This suggests that repeats in the normal
      and intermediate range could be involved in the rate of exhaustion of the ovarian
      primordial follicle pool and ultimately the timing of menopause. STUDY DESIGN,
      SIZE: Cross-sectional study in a population-based sample of 3611 Caucasian women
      with natural menopause. PARTICIPANTS/MATERIALS, SETTING, METHODS: The FMR1 CGG
      repeat number was determined by PCR amplification in 3611 women with a known age
      at natural menopause. A possible relation between CGG repeats in the normal and
      intermediate range (up to 55 repeats) and menopausal age were analysed in various
      ways, including linear regression analysis and analysis of variance. MAIN RESULTS
      AND THE ROLE OF CHANCE: The number of CGG repeats in the normal and intermediate
      range in the FMR1 gene was not associated with age at natural menopause. The mean
      age at menopause was 50.30 (+/- 4.2) years for women with <45 repeats and 50.64
      (+/- 3.4) years for women with intermediate-sized repeats (P = 0.37). Linear
      regression analysis of the number of CGG repeats showed no association with
      menopausal age (beta = 0.019, P = 0.16). LIMITATIONS, REASONS FOR CAUTION: In our
      cohort, age at menopause was self-reported and determined retrospectively. WIDER
      IMPLICATIONS OF THE FINDINGS: Earlier observations suggesting that the number of
      CGG repeats in the normal and intermediate range is associated with the
      individual variation of the ovarian ageing process could not be confirmed in the
      current, large sample size study. A relation between the number of CGG repeats in
      the normal and intermediate range and age at natural menopause appeared to be
      absent. This finding questions the role of CGG repeat sizes in the ovarian ageing
      process.

PMID- 23154069
TI  - Hypoxia and lost gills: respiratory ecology of a temperate larval damselfly.
AB  - Damselfly larvae, important predators and prey in many freshwater communities,
      may be particularly sensitive to hypoxia because their caudal lamellae (external
      gills) are frequently lost. In this study, we address how lost lamellae interact
      with low oxygen to affect respiration and behavior of the widespread North
      American damselfly Ischnura posita. Results showed no effect of lost lamellae on
      resting metabolic rate or critical oxygen tension. Ventilation behaviors
      increased only when dissolved oxygen (DO) was at or below 25% saturation and
      these behaviors were not affected by the number of lamellae. Use of the oxygen
      rich surface layer occurred almost exclusively at the lowest dissolved oxygen
      level tested (10% saturation, 2.0 kPa). Damselflies that were missing lamellae
      spent more time at the surface than individuals with intact lamellae. The
      negative relationship between body size and time at the surface, and the negative
      relationship between body mass and critical oxygen tension suggest that larger I.
      posita may be more hypoxia tolerant than smaller individuals. Overall, I. posita
      was minimally affected by missing lamellae and seems well-adapted to low DO
      habitats. Average critical oxygen tension was very low (0.48 kPa, 2.4%
      saturation), suggesting that individuals can maintain their metabolic rate across
      a broad range of DO, and behaviors changed only at DO levels below the hypoxia
      tolerance thresholds of many other aquatic organisms.

PMID- 23154070
TI  - Intervertebral disc degeneration in the dog. Part 2: chondrodystrophic and non
      chondrodystrophic breeds.
AB  - Dogs can be grouped into two distinct types of breed based on the predisposition
      to chondrodystrophy, namely, non-chondrodystrophic (NCD) and chondrodystrophic
      (CD). In addition to a different process of endochondral ossification, NCD and CD
      breeds have different characteristics of intravertebral disc (IVD) degeneration
      and IVD degenerative diseases. The anatomy, physiology, histopathology, and
      biochemical and biomechanical characteristics of the healthy and degenerated IVD
      are discussed in the first part of this two-part review. This second part
      describes the similarities and differences in the histopathological and
      biochemical characteristics of IVD degeneration in CD and NCD canine breeds and
      discusses relevant aetiological factors of IVD degeneration.

PMID- 23154071
TI  - Survival of Mycoplasma agalactiae and Mycoplasma mycoides subspecies capri in
      heat treated goat colostrum.
AB  - The viability of Mycoplasma agalactiae and Mycoplasma mycoides subsp. capri (Mmc)
      was assessed in goat colostrum treated at different temperatures. Samples of
      colostrum were inoculated with reference strains of M. agalactiae (PG2) and Mmc
      (PG3) and heated at 56 degrees C or 60 degrees C for 0, 30, 60, 90 or 120 min.
      Viable colonies of M. agalactiae were recovered after all treatments and there
      was a significant reduction in the concentration of viable M. agalactiae after 30
      min at 56 degrees C and 60 degrees C. No viable colonies of Mmc were observed
      after 60 min at 60 degrees C.

PMID- 23154073
TI  - Frequency-dependent entrainment of neocortical slow oscillation to repeated
      optogenetic stimulation in the anesthetized rat.
AB  - Local field potential (LFP) slow oscillation (<1Hz) is typically observed in the
      cortex during sleep or while under anesthesia and reflects synchronous
      activation/inactivation of the cortical neuron population. The oscillation can be
      entrained to repeated external sensory stimuli. To better understand the neural
      mechanism underlying slow-oscillation generation and its entrainment to external
      stimuli, we delivered optical stimulation to the cortex of anesthetized rats that
      exogenously expressed the light-sensitive cation channel channelrhodopsin-2
      (ChR2) and simultaneously monitored LFPs across cortical layers. We found that
      the LFPs could be effectively entrained to repeated optical stimulation at 1Hz in
      deep layers. A stimulus-triggered current-source density (CSD) analysis showed
      that the evoked oscillation had the same depth and temporal profile as the slow
      oscillations, indicating that both oscillations have the same neural mechanism.
      Optical stimulation primarily induced the transition from the cortical up to down
      state. These results suggest that the anesthetized rat cortex has an intrinsic
      mechanism that leads to oscillation near 1Hz; effective entrainment to the 1Hz
      stimulation reflects the resonated state of the cortex to that stimulus. Our
      study is the first to demonstrate optogenetic manipulation of cortical slow
      oscillation and provides a mechanistic explanation for slow-oscillation
      entrainment.

PMID- 23154072
TI  - In vitro and in vivo pharmacological profile of PL-3994, a novel cyclic peptide
      (Hept-cyclo(Cys-His-Phe-d-Ala-Gly-Arg-d-Nle-Asp-Arg-Ile-Ser-Cys)-Tyr-[Arg
      mimetic]-NH(2)) natriuretic peptide receptor-A agonist that is resistant to
      neutral endopeptidase and acts as a bronchodilator.
AB  - The pharmacological and airways relaxant profiles of PL-3994 (Hept-cyclo(Cys-His
      Phe-d-Ala-Gly-Arg-d-Nle-Asp-Arg-Ile-Ser-Cys)-Tyr-[Arg mimetic]-NH(2)), a novel
      natriuretic peptide receptor-A (NPR-A) agonist, were evaluated. PL-3994, a full
      agonist, has high affinity for recombinant human (h), dog, or rat NPR-As (K(i)s
      of 1, 41, and 10 nm, respectively), and produced concentration-dependent cGMP
      generation in human, dog and rat NPR-As (respective EC(50)s of 2, 3 and 14 nm).
      PL-3994 has a K(i) of 7 nm for hNPR-C but was without effect on cGMP generation
      in hNPR-B. PL-3994 (1 MUm) was without significant effect against 75 diverse
      molecular targets. PL-3994 or BNP, a natural NPR ligand, produced concentration
      dependent relaxation of pre-contracted guinea-pig trachea (IC(50)s of 42.7 and
      10.7 nm, respectively). PL-3994, and also BNP, (0.1 nm-100 MUm) elicited a
      potent, concentration-dependent but small relaxation of pre-contracted human
      precision-cut lung slices (hPCLS). Intratracheal PL-3994 (1-1000 MUg/kg) produced
      a dose-dependent inhibition of the bronchoconstrictor response evoked by
      aerosolized methacholine, but was without significant effect on cardiovascular
      parameters. PL-3994 was resistant to degradation by human neutral endopeptidase
      (hNEP) (92% remaining after 2 h), whereas the natural ligands, ANP and CNP, were
      rapidly metabolized (<=1% remaining after 2 h). PL-3994 is a potent, selective
      NPR agonist, resistant to NEP, with relaxant effects in guinea-pig and human
      airway smooth muscle systems. PL-3994 has the profile predictive of longer
      clinical bronchodilator activity than observed previously with ANP, and suggests
      its potential utility in the treatment of asthma, in addition to being a useful
      research tool to evaluate NPR biology.

PMID- 23154074
TI  - Electrophysiological monitoring in patients with tumors of the skull base treated
      by carbon-12 radiation therapy.
AB  - PURPOSE: To report the results of short-term electrophysiologic monitoring of
      patients undergoing (12)C therapy for the treatment of skull chordomas and
      chondrosarcomas unsuitable for radical surgery. METHODS AND MATERIALS:
      Conventional electroencephalogram (EEG) and retinal and cortical
      electrophysiologic responses to contrast stimuli were recorded from 30 patients
      undergoing carbon ion radiation therapy, within a few hours before the first
      treatment and after completion of therapy. Methodologies and procedures were
      compliant with the guidelines of the International Federation for Clinical
      Neurophysiology and International Society for Clinical Electrophysiology of
      Vision. RESULTS: At baseline, clinical signs were reported in 56.6% of subjects.
      Electrophysiologic test results were abnormal in 76.7% (EEG), 78.6% (cortical
      evoked potentials), and 92.8% (electroretinogram) of cases, without correlation
      with neurologic signs, tumor location, or therapy plan. Results on EEG, but not
      electroretinograms and cortical responses, were more often abnormal in patients
      with reported clinical signs. Abnormal EEG results and retinal/cortical responses
      improved after therapy in 40% (EEG), 62.5% (cortical potentials), and 70%
      (electroretinogram) of cases. Results on EEG worsened after therapy in one-third
      of patients whose recordings were normal at baseline. CONCLUSIONS: The
      percentages of subjects whose EEG results improved or worsened after therapy and
      the improvement of retinal/cortical responses in the majority of patients are
      indicative of a limited or negligible (and possibly transient) acute central
      nervous system toxicity of carbon ion therapy, with a significant beneficial
      effect on the visual pathways. Research on large samples would validate
      electrophysiologic procedures as a possible independent test for central nervous
      system toxicity and allow investigation of the correlation with clinical signs;
      repeated testing over time after therapy would demonstrate, and may help predict,
      possible late toxicity.

PMID- 23154076
TI  - 4pi non-coplanar liver SBRT: a novel delivery technique.
AB  - PURPOSE: To improve the quality of liver stereotactic body radiation therapy
      (SBRT) treatments, a novel 4pi framework was developed with accompanying
      algorithms to optimize non-coplanar beam orientations and fluences. The dose
      optimization is performed on a patient-specific deliverable beam geometry
      solution space, parameterized with patient and linear accelerator gantry
      orientations. METHODS AND MATERIALS: Beams causing collision between the gantry
      and the couch or patient were eliminated by simulating all beam orientations
      using a precise computer assisted design model of the linear accelerator and a
      human subject. Integrated beam orientation and fluence map optimizations were
      performed on remaining beams using a greedy column generation method. Testing of
      the new method was performed on 10 liver SBRT cases previously treated with 50 to
      60 Gy in 5 fractions using volumetric modulated arc therapy (VMAT). For each
      patient, both 14 and 22 non-coplanar fields were selected and optimized to meet
      the objective of >=95% of the planning target volume (PTV) covered by 100% of the
      prescription dose. Doses to organs at risk, normal liver volumes receiving <15
      Gy, integral dose, and 50% dose spillage volumes were compared against the
      delivered clinical VMAT plans. RESULTS: Compared with the VMAT plans, the 4pi
      plans yielded reduced 50% dose spillage volume and integral dose by 22% (range
      10%-40%) and 19% (range 13%-26%), respectively. The mean normal liver volume
      receiving <15 Gy was increased by 51 cc (range 21-107 cc) with a 31% reduction of
      the mean normal liver dose. Mean doses to the left kidney and right kidney and
      maximum doses to the stomach and spinal cord were on average reduced by 70%, 51%,
      67%, and 64% (P<=.05). CONCLUSIONS: This novel 4pi non-coplanar radiation
      delivery technique significantly improved dose gradient, reduced high dose
      spillage, and improved organ at risk sparing compared with state of the art VMAT
      plans.

PMID- 23154077
TI  - Lack of a dose-effect relationship for pulmonary function changes after
      stereotactic body radiation therapy for early-stage non-small cell lung cancer.
AB  - PURPOSE: To evaluate the influence of tumor size, prescription dose, and dose to
      the lungs on posttreatment pulmonary function test (PFT) changes after
      stereotactic body radiation therapy (SBRT) for early-stage non-small cell lung
      cancer (NSCLC). METHODS AND MATERIALS: The analysis is based on 191 patients
      treated at 5 international institutions: inclusion criteria were availability of
      pre- and post-SBRT PFTs and dose-volume histograms of the lung and planning
      target volume (PTV); patients treated with more than 1 SBRT course were excluded.
      Correlation between early (1-6 months, median 3 months) and late (7-24 months,
      median 12 months) PFT changes and tumor size, planning target volume (PTV) dose,
      and lung doses was assessed using linear regression analysis, receiver operating
      characteristics analysis, and Lyman's normal tissue complication probability
      model. The PTV doses were converted to biologically effective doses and lung
      doses to 2 Gy equivalent doses before correlation analyses. RESULTS: Up to 6
      months after SBRT, forced expiratory volume in 1 second and carbon monoxide
      diffusion capacity changed by -1.4% (95% confidence interval [CI], -3.4% to 0)
      and -7.6% (95% CI, -10.2% to -3.4%) compared with pretreatment values,
      respectively. A modest decrease in PFTs was observed 7-24 months after SBRT, with
      changes of -8.1% (95% CI, -13.3% to -5.3%) and -12.4% (95% CI, -15.5% to -6.9%),
      respectively. Using linear regression analysis, receiver operating characteristic
      analysis, and normal tissue complication probability modeling, all evaluated
      parameters of tumor size, PTV dose, mean lung dose, and absolute and relative
      volumes of the lung exposed to minimum doses of 5-70 Gy were not correlated with
      early and late PFT changes. Subgroup analysis based on pre-SBRT PFTs (greater or
      equal and less than median) did not identify any dose-effect relationship.
      CONCLUSIONS: This study failed to demonstrate a significant dose-effect
      relationship for changes of pulmonary function after SBRT for early-stage non
      small cell lung cancer.

PMID- 23154075
TI  - RTOG 0529: a phase 2 evaluation of dose-painted intensity modulated radiation
      therapy in combination with 5-fluorouracil and mitomycin-C for the reduction of
      acute morbidity in carcinoma of the anal canal.
AB  - PURPOSE: A multi-institutional phase 2 trial assessed the utility of dose-painted
      intensity modulated radiation therapy (DP-IMRT) in reducing grade 2+ combined
      acute gastrointestinal and genitourinary adverse events (AEs) of 5-fluorouracil
      (5FU) and mitomycin-C (MMC) chemoradiation for anal cancer by at least 15%
      compared with the conventional radiation/5FU/MMC arm from RTOG 9811. METHODS AND
      MATERIALS: T2-4N0-3M0 anal cancer patients received 5FU and MMC on days 1 and 29
      of DP-IMRT, prescribed per stage: T2N0, 42 Gy elective nodal and 50.4 Gy anal
      tumor planning target volumes (PTVs) in 28 fractions; T3-4N0-3, 45 Gy elective
      nodal, 50.4 Gy <= 3 cm or 54 Gy >3 cm metastatic nodal and 54 Gy anal tumor PTVs
      in 30 fractions. The primary endpoint is described above. Planned secondary
      endpoints assessed all AEs and the investigator's ability to perform DP-IMRT.
      RESULTS: Of 63 accrued patients, 52 were evaluable. Tumor stage included 54% II,
      25% IIIA, and 21% IIIB. In primary endpoint analysis, 77% experienced grade 2+
      gastrointestinal/genitourinary acute AEs (9811 77%). There was, however, a
      significant reduction in acute grade 2+ hematologic, 73% (9811 85%, P=.032),
      grade 3+ gastrointestinal, 21% (9811 36%, P=.0082), and grade 3+ dermatologic AEs
      23% (9811 49%, P<.0001) with DP-IMRT. On initial pretreatment review, 81%
      required DP-IMRT replanning, and final review revealed only 3 cases with normal
      tissue major deviations. CONCLUSIONS: Although the primary endpoint was not met,
      DP-IMRT was associated with significant sparing of acute grade 2+ hematologic and
      grade 3+ dermatologic and gastrointestinal toxicity. Although DP-IMRT proved
      feasible, the high pretreatment planning revision rate emphasizes the importance
      of real-time radiation quality assurance for IMRT trials.

PMID- 23154078
TI  - ATM polymorphisms predict severe radiation pneumonitis in patients with non-small
      cell lung cancer treated with definitive radiation therapy.
AB  - PURPOSE: The ataxia telangiectasia mutated (ATM) gene mediates detection and
      repair of DNA damage. We investigated associations between ATM polymorphisms and
      severe radiation-induced pneumonitis (RP). METHODS AND MATERIALS: We genotyped 3
      potentially functional single nucleotide polymorphisms (SNPs) of ATM (rs1801516
      [D1853N/5557G>A], rs189037 [-111G>A] and rs228590) in 362 patients with non-small
      cell lung cancer (NSCLC), who received definitive (chemo)radiation therapy. The
      cumulative severe RP probabilities by genotypes were evaluated using the Kaplan
      Meier analysis. The associations between severe RP risk and genotypes were
      assessed by both logistic regression analysis and Cox proportional hazard model
      with time to event considered. RESULTS: Of 362 patients (72.4% of non-Hispanic
      whites), 56 (15.5%) experienced grade >=3 RP. Patients carrying ATM rs189037
      AG/GG or rs228590 TT/CT genotypes or rs189037G/rs228590T/rs1801516G (G-T-G)
      haplotype had a lower risk of severe RP (rs189037: GG/AG vs AA, adjusted hazard
      ratio [HR] = 0.49, 95% confidence interval [CI], 0.29-0.83, P=.009; rs228590:
      TT/CT vs CC, HR=0.57, 95% CI, 0.33-0.97, P=.036; haplotype: G-T-G vs A-C-G,
      HR=0.52, 95% CI, 0.35-0.79, P=.002). Such positive findings remained in non
      Hispanic whites. CONCLUSIONS: ATM polymorphisms may serve as biomarkers for
      susceptibility to severe RP in non-Hispanic whites. Large prospective studies are
      required to confirm our findings.

PMID- 23154079
TI  - The interaction of nemorubicin metabolite PNU-159682 with DNA fragments
      d(CGTACG)(2), d(CGATCG)(2) and d(CGCGCG)(2) shows a strong but reversible binding
      to G:C base pairs.
AB  - The antitumor anthracycline nemorubicin is converted by human liver microsomes to
      a major metabolite, PNU-159682 (PNU), which was found to be much more potent than
      its parent drug toward cultured tumor cells and in vivo tumor models. The
      mechanism of action of nemorubicin appears different from other anthracyclines
      and until now is the object of studies. In fact PNU is deemed to play a dominant,
      but still unclear, role in the in vivo antitumor activity of nemorubicin. The
      interaction of PNU with the oligonucleotides d(CGTACG)(2), d(CGATCG)(2) and
      d(CGCGCG)(2) was studied with a combined use of (1)H and (31)P NMR spectroscopy
      and by ESI-mass experiments. The NMR studies allowed to establish that the
      intercalation between the base pairs of the duplex leads to very stable complexes
      and at the same time to exclude the formation of covalent bonds. Melting
      experiments monitored by NMR, allowed to observe with high accuracy the behaviour
      of the imine protons with temperature, and the results showed that the re
      annealing occurs after melting. The formation of reversible complexes was
      confirmed by HPLC-tandem mass spectra, also combined with endonuclease
      P1digestion. The MS/MS spectra showed the loss of neutral PNU before breaking the
      double helix, a behaviour typical of intercalators. After digestion with the
      enzyme, the spectra did not show any compound with PNU bound to the bases. The
      evidence of a reversible process appears from both proton and phosphorus NOESY
      spectra of PNU bound to d(CGTACG)(2) and to d(CGATCG)(2). The dissociation rate
      constants (k(off)) of the slow step of the intercalation process, measured by
      (31)P NMR NOE-exchange experiments, showed that the kinetics of the process is
      slower for PNU than for doxorubicin and nemorubicin, leading to a 10- to 20-fold
      increase of the residence time of PNU into the intercalation sites, with respect
      to doxorubicin. A relevant number of NOE interactions allowed to derive a model
      of the complexes in solution from restrained MD calculations. The conformation of
      PNU bound to the oligonucleotides was also derived from the coupling constant
      values.

PMID- 23154080
TI  - Environmental factors and their regulation of immunity in multiple sclerosis.
AB  - Epidemiological and clinical studies have shown that environmental factors such
      as infections, smoking and vitamin D are associated with the risk of developing
      multiple sclerosis (MS). Some of these factors also play a role in the MS disease
      course. We are currently beginning to understand how environmental factors may
      impact immune function in MS on a cellular and molecular level. Here we review
      epidemiological, clinical and basic immunological studies on the environmental
      factors, viral and parasitic infections, smoking, and vitamin D and relate
      epidemiological findings with their likely pathophysiology in MS.

PMID- 23154081
TI  - Anaphylaxis from ingestion of mites: pancake anaphylaxis.
AB  - Oral mite anaphylaxis is a new syndrome characterized by severe allergic symptoms
      occurring immediately after eating foods made with mite-contaminated wheat flour.
      This syndrome, which is more prevalent in tropical environments, is triggered
      more often by pancakes, and for that reason, it has been designated "the pancake
      syndrome." Because cooked foods are able to induce the symptoms, it has been
      suggested that thermoresistant allergens are involved in its pathogenesis. A
      variety of this syndrome can occur during physical exercise (dust mite ingestion
      associated exercise-induced anaphylaxis).

PMID- 23154083
TI  - Induction of severe systemic lupus erythematosus by TNF blockade and response to
      anti-IL-6 strategy.

PMID- 23154082
TI  - Obesity impairs apoptotic cell clearance in asthma.
AB  - BACKGROUND: Asthma in obese adults is typically more severe and less responsive
      to glucocorticoids than asthma in nonobese adults. OBJECTIVE: We sought to
      determine whether the clearance of apoptotic inflammatory cells (efferocytosis)
      by airway macrophages was associated with altered inflammation and reduced
      glucocorticoid sensitivity in obese asthmatic patients. METHODS: We investigated
      the relationship of efferocytosis by airway (induced sputum) macrophages and
      blood monocytes to markers of monocyte programming, in vitro glucocorticoid
      response, and systemic oxidative stress in a cohort of adults with persistent
      asthma. RESULTS: Efferocytosis by airway macrophages was assessed in obese (n=14)
      and nonobese (n=19) asthmatic patients. Efferocytosis by macrophages was 40%
      lower in obese than nonobese subjects, with a mean efferocytic index of 1.77 (SD,
      1.07) versus 3.00 (SD, 1.25; P<.01). A similar reduction of efferocytic function
      was observed in blood monocytes of obese participants. In these monocytes there
      was also a relative decrease in expression of markers of alternative (M2)
      programming associated with efferocytosis, including peroxisome proliferator
      activated receptor delta and CX3 chemokine receptor 1. Macrophage efferocytic
      index was significantly correlated with dexamethasone-induced mitogen-activated
      protein kinase phosphatase 1 expression (rho=0.46, P<.02) and baseline
      glucocorticoid receptor alpha expression (rho=0.44, P<.02) in PBMCs. Plasma 4
      hydroxynonenal levels were increased in obese asthmatic patients at 0.33 ng/mL
      (SD, 0.15 ng/mL) versus 0.16 ng/mL (SD, 0.08 ng/mL) in nonobese patients (P=.006)
      and was inversely correlated with macrophage efferocytic index (rho=-0.67,
      P=.02). CONCLUSIONS: Asthma in obese adults is associated with impaired
      macrophage/monocyte efferocytosis. Impairment of this anti-inflammatory process
      is associated with altered monocyte/macrophage programming, reduced
      glucocorticoid responsiveness, and systemic oxidative stress.

PMID- 23154086
TI  - Molecular pathways: regulation of metabolism by RB.
AB  - The discovery of the retinoblastoma (RB-1) gene as a tumor suppressor that is
      disrupted in a majority of human cancers either via direct or indirect genetic
      alterations has resulted in increased interest in its functions and downstream
      effectors. Although the canonical pathway that links this tumor suppressor to
      human cancers details its interaction with the E2F transcription factors and cell
      cycle progression, recent studies have shown an essential role for RB-1 in the
      suppression of glycolytic and glutaminolytic metabolism. Characterization of the
      precise metabolic transporters and enzymes suppressed by the RB-E2F axis should
      enable the identification of small molecule antagonists that have selective and
      potent antitumor properties.

PMID- 23154084
TI  - Examination of the relationship between variation at 17q21 and childhood wheeze
      phenotypes.
AB  - BACKGROUND: Genome-wide association studies have identified associations of
      genetic variants at 17q21 near ORMDL3 with childhood asthma. OBJECTIVES: We
      sought to determine whether associations in this region are specific to
      particular asthma phenotypes and specific to ORMDL3. METHODS: We examined
      associations between 244 independent single nucleotide polymorphisms (SNPs) plus
      13 previously identified asthma-related SNPs in the region between 34 and 36 Mb
      on chromosome 17 and early wheezing phenotypes, doctor-diagnosed asthma and atopy
      at 71/2 years, and bronchial hyperresponsiveness and lung function at 81/2 years
      in 7045 children from the Avon Longitudinal Study of Parents and Children birth
      cohort study. With this, cis expression quantitative trait loci signals for the
      same SNPs were assessed in 875 samples across genes in the same region. RESULTS:
      The strongest evidence for phenotypic association was seen for persistent
      wheezing (rs8076131 near ORMDL3: relative risk ratio [RRR], 1.60 [95% CI, 1.40
      1.84], P = 1.4 * 10(-11); rs2305480 near GSDML: RRR, 1.60 [95% CI, 1.39-1.83], P
      = 1.5 * 10(-11); and rs9303277 near IKZF3: RRR, 1.57 [95% CI, 1.37-1.79], P = 4.4
      * 10(-11)). Similar but less precisely estimated effects were seen for
      intermediate-onset wheeze, but there was little evidence of associations with
      other wheezing phenotypes. There was some evidence of associations with bronchial
      hyperresponsiveness. SNPs across the whole region show strong evidence of
      association with differential levels of expression at GSDML, IKZF3, and MED24, as
      well as ORMDL3. CONCLUSIONS: Associations of SNPs in the 17q21 locus are specific
      to asthma and specific wheezing phenotypes and are not explained by associations
      with intermediate phenotypes, such as atopy or lung function.

PMID- 23154087
TI  - Epidemiological analysis of a cluster within the outbreak of Shiga toxin
      producing Escherichia coli serotype O104:H4 in Northern Germany, 2011.
AB  - In May 2011 one of the worldwide largest outbreaks of haemolytic uraemic syndrome
      (HUS) and bloody diarrhoea caused by Shiga toxin-producing Escherichia coli
      (STEC) serotype O104:H4 occurred in Germany. One of the most affected federal
      states was Lower Saxony. We present the investigation of a cluster of STEC and
      HUS cases within this outbreak by means of a retrospective cohort study. After a
      70th birthday celebration which took place on 7th of May 2011 among 72 attendants
      seven confirmed cases and four probable cases were identified, two of them
      developed HUS. Median incubation period was 10 days. Only 35 persons (48.6%)
      definitely answered the question whether they had eaten the sprouts that were
      used for garnishing the salad. Univariable analysis revealed different food
      items, depending on the case definition, with Odds Ratio (OR)>1 indicating an
      association with STEC infection, but multivariable logistic regression showed no
      increased risk for STEC infection for any food item and any case definition.
      Sprouts as the source for the infection had to be assumed based on the results of
      a tracing back of the delivery ways from the catering company to the sprouts
      producer who was finally identified as the source of the entire German outbreak.
      In this large outbreak several case-control studies failed to identify the source
      of infection.

PMID- 23154088
TI  - Renewed efforts are needed to curb antibiotic resistance.

PMID- 23154089
TI  - Family of patient who died during a clinical trial receive a six figure
      settlement.

PMID- 23154090
TI  - Status of women is central to reducing child mortality in India, report says.

PMID- 23154091
TI  - Common mechanisms of auditory hallucinations-perfusion studies in epilepsy.
AB  - Auditory hallucinations (AH) occur in various neurological and psychiatric
      disorders. In psychosis, increased neuronal activity in the primary auditory
      cortex (PAC) contributes to AH. We investigated functional neuroanatomy of
      epileptic hallucinations by measuring cerebral perfusion in three patients with
      AH during simple partial status epilepticus. Hyperperfusion in the temporal lobe
      covering the PAC occurred in all patients. Our perfusion data support the
      hypothesis of PAC being a constituting element in the genesis of AH independent
      of their aetiology.

PMID- 23154092
TI  - Frontoparietal attentional network activation differs between smokers and
      nonsmokers during affective cognition.
AB  - Smoking withdrawal-induced disruption of affect and cognition is associated with
      dysregulated prefrontal brain function, although little is known regarding the
      neural foci of smoker-nonsmoker differences during affective cognition. Thus, the
      current study used functional magnetic resonance imaging (fMRI) to identify
      smoker-nonsmoker differences in affective cognition. Thirty-four healthy
      volunteers (17 smokers, 17 nonsmokers) underwent fMRI during an affective Stroop
      task (aST). The aST includes emotional cue-reactivity trials, and response
      selection trials that contain either neutral or negative emotional distractors.
      Smokers had less activation during negative cue-reactivity trials in regions
      subserving emotional awareness (i.e., posterior cingulate), inhibitory control
      (i.e., inferior frontal gyrus) and conflict resolution (i.e., anterior
      cingulate); during response-selection trials with negative emotional distractors,
      smokers had greater activation in a frontoparietal attentional network (i.e.,
      middle frontal and supramarginal gyri). Exploratory analyses revealed that task
      accuracy was positively correlated with anterior cingulate cortex and inferior
      frontal gyrus response on fMRI. These findings suggests that chronic nicotine use
      may reduce inhibitory control and conflict resolution of emotional distraction,
      and result in recruiting additional attentional resources during emotional
      interference on cognition.

PMID- 23154094
TI  - Abnormal neural activity in partially remitted late-onset depression: an fMRI
      study of one-back working memory task.
AB  - Only half of the geriatric patients with major depressive disorder (MDD) can
      reach full remission after treatment of half a year. This study was designed to
      examine the neural responses in the partial responders of late-onset MDD. We used
      3-Tesla functional magnetic resonance imaging to assess the patterns of cerebral
      activation/deactivation in the performance of a one-back version of the n-back
      working memory task. We recruited 14 major depressive patients who reached
      partial remission after at least half a year of pharmacological intervention,
      compared with 14 non-depressive controls. There were no significant between-group
      differences in the demographical profiles and working memory performance, which
      was true for both accuracy and reaction time. Brain masks encompassing the neural
      responses of activation/deactivation were constructed from the non-depressive
      controls. The depressive group shows enhanced activities at left middle frontal
      and left parietal regions, and reduced deactivation at several temporal regions
      and left amygdala within the masks. Besides, the depressive group activates extra
      neural nodes at middle frontal and middle temporal regions outside the masks. The
      neural responses in the left amygdala are significantly correlated with the
      severity of depression and comorbid anxiety. The loss of deactivation in the left
      amygdala and the temporal areas in cognitive endeavor may be related to the
      refractoriness to treatment. 

PMID- 23154093
TI  - Neurometabolite concentration and clinical features of chronic alcohol use: a
      proton magnetic resonance spectroscopy study.
AB  - Chronic, heavy alcohol consumption may affect the concentration of
      neurometabolites assessed with proton magnetic resonance spectroscopy ((1)H-MRS).
      We investigated the largest sample reported to date (N=213) with the primary goal
      of determining how specific clinical features impact neurometabolite
      concentrations in an anterior cingulate gray matter voxel. This community
      dwelling sample included both treatment-seeking and non-treatment-seeking
      individuals. A healthy control group (N=66) was matched for age and education. In
      multivariate analyses predicting neurometabolite concentrations, the heavy
      drinking group had greater concentrations overall. An age by group interaction
      was noted, as group difference across neurometabolites increased with age. More
      years drinking, but not more drinks per drinking day (DPDD), predicted greater
      concentrations of choline-containing compounds (Cho), creatine-phosphocreatine
      (Cre), glutamate-glutamine (Glx), and N-acetyl-aspartate (NAA). The effects of
      other clinical variables (depression, cigarette smoking, marijuana use) were
      negligible. After controlling for DPDD and years drinking, treatment-seeking
      status had no impact on neurometabolites. In the very oldest portion of the
      sample (mean age=50), however, a negative relationship was seen between NAA and
      years drinking. These results suggest that the nature of neurometabolite
      abnormalities in chronic heavy drinkers may vary as a function of duration of
      abuse.

PMID- 23154095
TI  - Recent binge drinking predicts smaller cerebellar volumes in adolescents.
AB  - The current study examined the effects of recent binge drinking on cerebellar
      morphometry in a sample of healthy adolescents. Participants were 106 teenagers
      (46 bingers and 60 controls) aged 16-19 who received a high-resolution magnetic
      resonance imaging (MRI) scan. FreeSurfer segmented and quantified the volume of
      each cerebellum. Maximum drinks during a binge in the past 3 months and duration
      since last binge were examined as predictors of cerebellar volume, after
      controlling for potentially confounding variables. In the 106 teens, higher peak
      drinks predicted smaller left hemisphere cerebellar gray and whitematter, and
      right hemisphere cerebellar gray matter, and marginally predicted smaller right
      hemisphere cerebellar white matter. Gender did not moderate these effects. More
      intense adolescent binge drinking is linked to smaller cerebellar volumes even in
      healthy teens, above and beyond variability attributable to risk factors for
      binge drinking. Longitudinal research is needed to see if cerebellar volumes
      worsen with protracted drinking and recover with abstinence. Interventions aimed
      at improving brain structure in adolescent binge drinkers are necessary given the
      high prevalence of risky drinking in youth.

PMID- 23154096
TI  - Absence of anatomic corpus callosal abnormalities in childhood-onset
      schizophrenia patients and healthy siblings.
AB  - The corpus callosum (CC) has been implicated in the pathogenesis of
      schizophrenia, and CC deficits have been reported in adults with schizophrenia.
      We explored the developmental trajectory of the corpus callosum in childhood
      onset schizophrenia (COS) patients, their healthy siblings (SIB) and healthy
      volunteers. We obtained 235 anatomic brain magnetic resonance imaging (MRI) scans
      from 98 COS patients, 153 scans from 71 of their healthy siblings, and 253 scans
      from 100 age- and gender-matched healthy volunteers, across ages 9-30 years. The
      volumes of five sub-regions of the CC were calculated using FreeSurfer, and
      summed to give the total volume. Longitudinal data were examined using mixed
      model regression analysis. There were no significant differences for the total or
      sub-regional CC volumes between the three groups. There were also no significant
      differences between the groups for developmental trajectory (slope) of the CC.
      This is the largest longitudinal study of CC development in schizophrenia and the
      first COS study of the CC to include healthy siblings. Overall, CC volume and
      growth trajectory did not differ between COS patients, healthy siblings, or
      healthy volunteers. These results suggest that CC development, at least at a
      macroscopic level, may not be a salient feature of schizophrenia.

PMID- 23154097
TI  - Silent brain infarcts: a cause of depression in the elderly?
AB  - The present study included 1047 elderly participants. At baseline, brain magnetic
      resonance imaging (MRI) was performed to detect infarcts and white matter
      lesions; further, depressive disorders were assessed. Participants were followed
      up during 3.6 years to determine incident and recurrent depression. We found an
      increased risk of recurrent depression associated with silent brain infarcts.

PMID- 23154098
TI  - Neural functional and structural correlates of childhood maltreatment in women
      with intimate-partner violence-related posttraumatic stress disorder.
AB  - Childhood maltreatment (CM) is a strong risk factor for development of
      posttraumatic stress disorder (PTSD) upon adult exposure to extreme adverse
      events. However, the neural underpinnings of this relationship are not well
      understood. Here, we test the hypothesis that severity of CM history is
      positively correlated with emotion-processing limbic and prefrontal brain
      activation/connectivity and negatively correlated with prefrontal gray matter
      volumes in women with PTSD due to intimate-partner violence (IPV-PTSD). Thirty
      three women with IPV-PTSD underwent structural and functional magnetic resonance
      imaging while completing a facial emotion processing task. Multivariate
      regressions examined the relationship of CM to patterns of activation,
      connectivity, and gray matter volumes. CM severity was: (a) positively correlated
      with ventral ACC activation while processing angry faces; (b) negatively
      correlated with dorsal ACC and insula activation while processing fear and angry
      faces, arising from positive correlations with the shape-matching baseline; (c)
      positively correlated with limbic-prefrontal connectivity while processing fear
      faces but negatively correlated with amygdalo-insular connectivity while
      processing fear and angry; and (d) negatively correlated with prefrontal gray
      matter volumes. These results suggest CM exposure may account for variability in
      limbic/prefrontal brain function and prefrontal structure in adulthood PTSD and
      offer one potential mechanism through which CM confers risk to future development
      of PTSD.

PMID- 23154099
TI  - Glutamate system genes and brain volume alterations in pediatric obsessive
      compulsive disorder: a preliminary study.
AB  - Obsessive-compulsive disorder (OCD) has been associated with regional volumetric
      brain abnormalities, which provide promising intermediate phenotypes of the
      disorder. In this study, volumes of brain regions selected for a priori evidence
      of association with OCD (orbitofrontal cortex (OFC), anterior cingulate cortex
      (ACC), thalamus, caudate, putamen, globus pallidus and pituitary) were measured
      using structural magnetic resonance imaging (MRI) in 20 psychotropic-naive
      pediatric OCD patients. We examined the association between these regional brain
      volumes and a total of 519 single nucleotide polymorphisms (SNPs) from nine
      glutamatergic candidate genes (DLGAP1, DLGAP2, DLGAP3, GRIN2B, SLC1A1, GRIK2,
      GRIK3, SLITRK1 and SLITRK5). These genes were selected based on either previous
      reported association with OCD in humans or evidence from animal models of OCD.
      After correcting for multiple comparisons by permutation testing, no SNP remained
      significantly associated with volumetric changes. The strongest trend toward
      association was identified between two SNPs in DLGAP2 (rs6558484 and rs7014992)
      and OFC white matter volume. Our other top ranked association findings were with
      ACC, OFC and thalamus. These preliminary results suggest that sequence variants
      in glutamate candidate genes may be associated with structural neuroimaging
      phenotypes of OCD.

PMID- 23154101
TI  - [Reply to the letter "Comments on peritonsillar infections: a prospective study
      of 100 consecutive cases"].

PMID- 23154100
TI  - Interaction between serotonin transporter and dopamine D2/D3 receptor radioligand
      measures is associated with harm avoidant symptoms in anorexia and bulimia
      nervosa.
AB  - Individuals with anorexia nervosa (AN) and bulimia nervosa (BN) have alterations
      of measures of serotonin (5-HT) and dopamine (DA) function, which persist after
      long-term recovery and are associated with elevated harm avoidance (HA), a
      measure of anxiety and behavioral inhibition. Based on theories that 5-HT is an
      aversive motivational system that may oppose a DA-related appetitive system, we
      explored interactions of positron emission tomography (PET) radioligand measures
      that reflect portions of these systems. Twenty-seven individuals recovered (REC)
      from eating disorders (EDs) (7 AN-BN, 11 AN, 9 BN) and nine control women (CW)
      were analyzed for correlations between [(11)C]McN5652 and [(11)C]raclopride
      binding. There was a significant positive correlation between [(11)C]McN5652
      binding potential (BP(non displaceable(ND))) and [(11)C]Raclopride BP(ND) for the
      dorsal caudate, antero-ventral striatum (AVS), middle caudate, and ventral and
      dorsal putamen. No significant correlations were found in CW. [(11)C]Raclopride
      BP(ND), but not [(11)C]McN5652 BP(ND), was significantly related to HA in REC
      EDs. A linear regression analysis showed that the interaction between
      [(11)C]McN5652 BP(ND) and [(11)C]raclopride BP(ND) in the dorsal putamen
      significantly predicted HA. This is the first study using PET and the
      radioligands [(11)C]McN5652 and [(11)C]raclopride to show a direct relationship
      between 5-HT transporter and striatal DA D2/D3 receptor binding in humans,
      supporting the possibility that 5-HT and DA interactions contribute to HA
      behaviors in EDs.

PMID- 23154103
TI  - d-Dimer and simplified pulmonary embolism severity index in relation to right
      ventricular function.
AB  - BACKGROUND: Right ventricular (RV) involvement in pulmonary embolism (PE) is an
      ominous sign. The aim of this study was to investigate the extent to which the d
      dimer level or simplified PE severity index (sPESI) indicates RV dysfunction in
      patients with preserved systemic arterial pressure. METHODS: Right ventricular
      function was studied in 34 consecutive patients with acute nonmassive PE by
      echocardiography including Doppler tissue imaging within 24 hours after arrival
      to the hospital. d-Dimer and sPESI were assessed upon arrival. RESULTS: d-Dimer
      correlated with RV pressure (Rs, 0.60; P < .001) and pulmonary vascular
      resistance (PVR; Rs, 0.68; P < .0001) and tended to be related to myocardial
      performance index (MPI; Rs, 0.31; P = .067). Compared to a level less than 3.0
      mg/L, patients with d-dimer 3.0 mg/L or higher had lower systolic tricuspid
      annular velocity (11.3 +/- 2.7 vs 13.5 +/- 2.7 cm/s; P < .05), a prolonged MPI
      (0.8 +/- 0.3 vs 0.5 +/- 0.2; P < .01), increased RV pressure (58 +/- 13 vs 37 +/-
      12 mm Hg; P < .001), and increased PVR (3.3 +/- 1.1 vs 1.8 +/- 0.4 Woods units; P
      < .001). Patients in the high-risk sPESI group had higher filling pressure than
      those in the low risk sPESI group. CONCLUSIONS: In the acute stage of PE, a d
      dimer level 3 mg/L or higher may identify nonmassive PE patients with RV
      dysfunction and thereby help to determine their risk profile. We found no
      additional value for sPESI in this context.

PMID- 23154102
TI  - Cerebral regional oxygen saturation monitoring in pediatric malfunctioning shunt
      patients.
AB  - BACKGROUND: Shunt malfunction produces increased intracranial pressure causing
      decreased cerebral regional perfusion and tissue O(2)sat. Cerebral regional
      oxygen saturation (rSO(2)) by near-infrared spectroscopy represents tissue
      perfusion and oxygen saturation. Cerebral rSO(2) is used to detect cerebral
      ischemia in pediatric clinical settings. OBJECTIVE: The objective of the study
      was to determine the reliability of cerebral rSO(2) in pediatric malfunctioning
      shunt. METHODS: A prospective observational study of pediatric patients presented
      to the pediatric emergency department was conducted. Confirmed malfunctioning
      shunt subjects had cerebral rSO(2) monitoring. RESULTS: A total of 131
      malfunctioning shunt subjects had cerebral rSO(2) monitoring. Patient's central
      trend and intrasubject variability of cerebral rSO(2) readings for left and right
      probe and malfunction sites (n = 131) are as follows:  Intrasubject left and
      right rSO(2) Pearson correlation was -0.46 to 0.98 (mean +/- SD, 0.35 +/- 0.34;
      median, 0.34; interquartile range, 0.06-0.61). The correlation coefficients of 99
      subjects between left and right rSO(2) was significantly different (P < .001),
      suggesting that intrasubjects' left and right rSO(2) are highly correlated.
      Sample mean difference between left and right rSO(2) were -1.7% (95% confidence
      interval [CI], -1.8 to -1.6; P < .001) supporting overall left lower than right.
      Intraclass correlation for left rSO(2) was 87.4% (95% CI, 87.2%-87.6%), and that
      for right rSO(2) was 83.8% (95% CI, 83.8%-84%), showing intersubject differences
      accounting for the variation, and relative to intersubject variation,
      intrasubjects readings are consistent. Intrasubjects, left and right rSO(2)
      highly correlate and are asymmetrical. Left and right rSO(2) are consistent in
      intrasubject with large rSO(2) variations in trend and variability across
      subjects. CONCLUSION: This study demonstrates reliable cerebral rSO(2) readings
      in subjects with malfunctioning shunts, with asymmetrical cerebral rSO(2)
      hemispheric dynamics within subjects.

PMID- 23154104
TI  - Retrospective time series analysis of veterinary laboratory data: preparing a
      historical baseline for cluster detection in syndromic surveillance.
AB  - The practice of disease surveillance has shifted in the last two decades towards
      the introduction of systems capable of early detection of disease. Modern
      biosurveillance systems explore different sources of pre-diagnostic data, such as
      patient's chief complaint upon emergency visit or laboratory test orders. These
      sources of data can provide more rapid detection than traditional surveillance
      based on case confirmation, but are less specific, and therefore their use poses
      challenges related to the presence of background noise and unlabelled temporal
      aberrations in historical data. The overall goal of this study was to carry out
      retrospective analysis using three years of laboratory test submissions to the
      Animal Health Laboratory in the province of Ontario, Canada, in order to prepare
      the data for use in syndromic surveillance. Daily cases were grouped into
      syndromes and counts for each syndrome were monitored on a daily basis when
      medians were higher than one case per day, and weekly otherwise. Poisson
      regression accounting for day-of-week and month was able to capture the day-of
      week effect with minimal influence from temporal aberrations. Applying Poisson
      regression in an iterative manner, that removed data points above the predicted
      95th percentile of daily counts, allowed for the removal of these aberrations in
      the absence of labelled outbreaks, while maintaining the day-of-week effect that
      was present in the original data. This resulted in the construction of time
      series that represent the baseline patterns over the past three years, free of
      temporal aberrations. The final method was thus able to remove temporal
      aberrations while keeping the original explainable effects in the data, did not
      need a training period free of aberrations, had minimal adjustment to the
      aberrations present in the raw data, and did not require labelled outbreaks.
      Moreover, it was readily applicable to the weekly data by substituting Poisson
      regression with moving 95th percentiles.

PMID- 23154105
TI  - The impact of animal introductions during herd restrictions on future herd-level
      bovine tuberculosis risk.
AB  - In Ireland new cases of bovine tuberculosis (bTB) are detected using both field
      (with the single intradermal comparative tuberculin test (SICTT)) and abattoir
      surveillance. Once a new case has been detected, herd restrictions, including
      restrictions on animal movements into and out of the herd, are implemented until
      the herd has passed two consecutive clear tests. While a herd is restricted,
      there may be several reasons why it may be desirable to introduce new stock, such
      as enabling routine management practices to continue 'as near to normal'. In
      Ireland, introduction of animals during a bTB episode is permitted under specific
      conditions, with permission from the local veterinary office. The objectives of
      this study were (1) to provide an overview of movement events associated with
      each bTB episode, (2) to determine whether introduction of animals during a bTB
      episode is associated with increased future bTB risk and (3) to identify the
      practices relating to the introduction of animals that are the most risky. All
      herds that were not restricted at the start of 2006, but experienced a bTB
      episode during 2006 with 2 or more SICTT standard reactors (the eligible bTB
      episode) were included in the study. We calculated the number of extended
      eligible bTB episodes and subsequent bTB episodes that could be directly
      attributed to introduced animals. The main outcome of interest was the time from
      de-restriction of the eligible bTB episode to the start of a subsequent bTB
      episode or the date of the last test prior to the end of the study (31 December
      2010). Cox proportional-hazard models were developed, each using a different
      introduction variable: introduced animals during an episode (yes/no), introduced
      animals prior to the first retest/first clear test, time from start of episode
      until first animals introduced and number of animals introduced during the
      episode. Only a small proportion of subsequent bTB episodes (1.8%) or extended
      eligible bTB episodes (2.7%) could be directly attributed to introduced animals.
      The results highlight an increased risk of a subsequent bTB episode among only a
      subset of herds that introduced animals during the eligible bTB episode.
      Specifically, herds that introduced animals early during the eligible bTB episode
      were at significantly greater future bTB risk than herds where animals were only
      introduced later. To illustrate, herds that introduced animals after the first
      retest did not have a significantly different risk compared to herds that did not
      introduce animals at all. In contrast, herds that did introduce animals prior to
      the first retest had 1.5 times higher risk of a subsequent bTB episode. Future
      practices concerning the introduction of animals during an episode now need to be
      reviewed.

PMID- 23154106
TI  - Prospects for cost reductions from relaxing additional cross-border measures
      related to livestock trade.
AB  - Compared with the domestic trade in livestock, intra-communal trade across the
      European Union (EU) is subject to costly, additional veterinary measures. Short
      distance transportation just across a border requires more measures than long
      distance domestic transportation, while the need for such additional cross-border
      measures can be questioned. This study examined the prospects for cost reductions
      from relaxing additional cross-border measures related to trade within the cross
      border region of the Netherlands (NL) and Germany (GER); that is, North Rhine
      Westphalia and Lower Saxony. The study constructed a deterministic spread-sheet
      cost model to calculate the costs of both routine veterinary measures (standard
      measures that apply to both domestic and cross-border transport) and additional
      cross-border measures (extra measures that only apply to cross-border transport)
      as applied in 2010. This model determined costs by stakeholder, region and
      livestock sector, and studied the prospects for cost reduction by calculating the
      costs after the relaxation of additional cross-border measures. The selection
      criteria for relaxing these measures were (1) a low expected added value on
      preventing contagious livestock diseases, (2) no expected additional veterinary
      risks in case of relaxation of measures and (3) reasonable cost-saving
      possibilities. The total cost of routine veterinary measures and additional cross
      border measures for the cross-border region was ?22.1 million, 58% (?12.7
      million) of which came from additional cross-border measures. Two-thirds of this
      ?12.7 million resulted from the trade in slaughter animals. The main cost items
      were veterinary checks on animals (twice in the case of slaughter animals),
      export certification and control of export documentation. Four additional cross
      border measures met the selection criteria for relaxation. The relaxation of
      these measures could save ?8.2 million (?5.0 million for NL and ?3.2 million for
      GER) annually. Farmers would experience the greatest savings (99%), and most
      savings resulted from relaxing additional cross-border measures related to
      poultry (48%), mainly slaughter broilers (GER), and pigs (48%), mainly slaughter
      pigs (NL). In particular, the trade in slaughter animals (dead-end hosts) is
      subject to measures, such as veterinary checks on both sides of the border that
      might not contribute to preventing contagious livestock diseases. Therefore, this
      study concludes that there are several possibilities for reducing the costs of
      additional cross-border measures in both countries.

PMID- 23154107
TI  - Impact of demographic characteristics in pet ownership: modeling animal count
      according to owners income and age.
AB  - Pet owner characteristics such as age, gender, income/social class, marital
      status, rural/urban residence and household type have been shown to be associated
      with the number of owned pets. However, few studies to date have attempted to
      evaluate these associations in Brazil. Accordingly, the aim of this study was to
      evaluate the association between age and income of owners and the number of owned
      dogs and cats in a Brazilian urban center. Pinhais, metropolitan area of
      Curitiba, Southern Brazil, the seventh largest city in Brazil, was chosen for
      this study. Questionnaires were administered door-to-door between January and
      February 2007 and data were analyzed by zero-inflated negative binomial (ZINB)
      models. A total of 13,555 of 30,380 (44.62%) households were interviewed. The
      majority (62.43%) of households reported having one or more dogs, with one or two
      dogs being the most common (29.97% and 19.71%, respectively). Cat ownership per
      household was much lower (P=0.001) than dog ownership, with 90% of the households
      reported having no owned cats. ZINB analyses indicated that income is not
      associated with the number of both dogs and cats among households that have pets.
      However, households from higher income categories were more likely to have dogs
      (but not cats) when compared to the lowest income category (P<0.05),
      contradicting a common belief that the poorer the family, the more likely they
      have pets. Certain age categories were significantly associated with the number
      of dogs or cats in households that have pets. In addition, most age categories
      were significantly associated with having dogs and/or cats (P<0.05). In
      conclusion, our study has found that age but not household income is associated
      with the number of dogs or cats in households that have pets; higher income
      households were more likely to have dogs when compared to low-income households.

PMID- 23154108
TI  - [Facial edema].

PMID- 23154109
TI  - [Standardized geriatric assessment or comprehensive gerontological assessment:
      where do we stand?].
AB  - The concept of comprehensive gerontological assessment is a foundation of modern
      geriatrics. Our focus was to try to clarify the underlying concepts, assess the
      level of evidence and clarify the issues still under debate. The concept implies
      the definition of an interdisciplinary process for a multidimensional assessment
      in order to produce a coordinated plan. The central notion is that the
      systematization of this multidimensionality and interdisciplinarity needs the
      establishment of dedicated process (meeting tools, clinical information system,
      etc.). Following dimensions should be covered: health, social, economic,
      environmental and psychological. Any assessment process that could lead to
      forgetting one of its dimensions cannot be viewed as a comprehensive
      gerontological assessment. The level of evidence is higher in hospital acute
      inpatient unit but it is still low in all other areas of health care but the
      scattered data in the literature argues for qualitative benefits (improved
      quality of care or quality of life). The questions that remain are numerous
      including the choice of strategy for initial evaluation (maximum versus minimum;
      from the outset by many professionals versus graduated based on the minimum
      initial evaluation), the choice of tool, the optimal location, the required
      intensity of monitoring and the ideal target population.

PMID- 23154110
TI  - [Kidney involvement in sarcoidosis].
AB  - Sarcoidosis is a chronic multisystemic inflammatory disorder of unknown etiology,
      characterized by the presence of non-necrotizing epithelioid and giant cell
      granulomas. Various renal manifestations have been reported in patients with
      sarcoidosis. Disorders of bone and mineral metabolism related to the
      overexpression of 25-hydroxyvitamin-D1alpha-hydroxylase by alveolar and granuloma
      macrophages are frequently associated with sarcoidosis. Hypercalcemia and
      hypercalciuria are a major cause of renal injury predisposing to pre renal
      azotemia, acute tubular necrosis, nephrolithiasis and nephrocalcinosis.
      Therapeutic management of hypercalcemia includes preventive measures (limited
      sunlight exposure, limited vitamin D and calcium intakes, and adequate hydration)
      and specific treatment in cases of severe hypercalcemia (corticosteroid therapy,
      chloroquine or ketoconazole). Granulomatous tubulointerstitial nephritis is the
      most common renal lesion associated with sarcoidosis leading to end stage renal
      disease in some patients. In these cases, interstitial fibrosis seems to appear
      early in the course of sarcoidosis and is a major prognostic factor requiring
      rapid corticosteroid therapy to reduce the risk of severe renal impairment.
      Membranous nephropathy seems to be the most frequent glomerular disease that may
      occur in association with sarcoidosis. Among kidney allograft recipients, the
      risk of recurrence of granulomatous tubulointerstitial nephritis is high and may
      have a negative impact on the graft survival. 

PMID- 23154111
TI  - [Aspirin for secondary prevention of venous thromboembolism. WARFASA: far from
      being conclusive].

PMID- 23154112
TI  - Cardiorespiratory variability following repeat acute hypoxia in the conscious SHR
      versus two normotensive rat strains.
AB  - A link between exaggerated chemoreceptor sensitivity and hypertension has been
      documented in the spontaneously hypertensive rat (SHR) but has also been
      questioned when comparisons with normotensive strains other than the Wistar Kyoto
      (WKY) rat are made. To further evaluate the link between hypertension and
      chemoreflex sensitivity, changes in cardiorespiratory variability in response to
      three successive bouts of 5 min of hypoxia (21%->10%) were evaluated in conscious
      male SHR, and WKY and Sprague Dawley (SD) rats (n=7-8/group). In response to the
      first bout of hypoxia, the change in respiratory frequency (RF) was greatest in
      the SHR, but the increase in mean arterial pressure (MAP) was similar in both
      SHRs and WKY rats and all strains demonstrated a similar rise in heart rate (HR).
      All strains showed some level of response accommodation during subsequent bouts
      of hypoxia. Spectral analysis of HR variability identified a significant
      difference in high frequency (HF) power between strains during hypoxia, including
      an increase in HF power in the WKY rats, a decrease in the SHRs and little
      overall change in the SD rats. Alternatively, all strains demonstrated a rise in
      systolic arterial pressure (SAP) variability in the low frequency (LF) range in
      response to hypoxia but the increase was greatest in the SHR. Since SAP LF power
      is linked to vasosympathetic tone, these results support the hypothesis that
      essential hypertension is linked to exaggerated sympathetic responses to
      chemoreceptor stimulation but confirm that estimation of augmented reflex
      function cannot be determined by quantifying simple changes in MAP or HR.

PMID- 23154113
TI  - [Prevalence of metabolic syndrome, its relationship with mental health (anger)
      and sociodemographic characteristics in women residing in central district of
      Malatya: a cross-sectional observational study].

PMID- 23154114
TI  - The difficulties during transcatheter aortic valve implantation and appropriate
      precautions.

PMID- 23154115
TI  - A challenging case of transcatheter aortic valve implantation under left main
      coronary artery protection.

PMID- 23154116
TI  - Left atrial appendix thrombus presenting with acute coronary syndrome in a
      patient with rheumatic mitral stenosis.

PMID- 23154117
TI  - Psychological problems in patients awaiting coronary angiography: a preliminary
      study.

PMID- 23154118
TI  - Double outlet right ventricle: Fallot type or non-Fallot type.

PMID- 23154119
TI  - [Video of minimally invasive totally endoscopic surgical treatment of a myxoma on
      the mitral valve].

PMID- 23154120
TI  - [Electrocardiography in a patient with orthotopic cardiac transplantation].

PMID- 23154121
TI  - The light of inflammation in the darkness of the coronary slow flow phenomenon.

PMID- 23154122
TI  - An interview with Prof. Dr. Richard Sutton. Interview by Sema Guneri.

PMID- 23154123
TI  - Long-term outcome of paediatric-onset multiple sclerosis: a population-based
      study.
AB  - BACKGROUND: Age of onset of multiple sclerosis (MS) peaks in the 3rd and 4th
      decades and is rarely less than 18. Robust longitudinal studies in paediatric
      onset MS (POMS) are limited, and a clearer understanding of outcome could
      optimise management strategies. METHODS: Patients with disease onset <18 years
      were identified from a prospective population-based register. Clinical features
      including presenting symptoms, time to Expanded Disability Status Scale (EDSS)
      4.0, 6.0 and 8.0 and onset of secondary progression were compared with patients
      with adult-onset MS (AOMS). RESULTS: 111 POMS patients were identified from a
      cohort of 2068. No significant differences in sex ratio, familial recurrence,
      relapse rate, ethnicity or clinical symptoms at presentation were identified
      between POMS and AOMS. However, interval to second relapse was longer (5 vs 2.6
      years, p=0.04) and primary progressive disease was less common (0.9% vs 8.5%,
      p=0.003) in POMS than in AOMS. POMS patients also took longer to develop
      secondary progressive disease (32 vs 18 years, p=0.0001) and to reach disability
      milestones (EDSS 4.0, 23.8 vs 15.5 years, p<0.0001; EDSS 6.0, 30.8 vs 20.4 years,
      p<0.0001; EDSS 8.0, 44.7 vs 39 years, p=0.02), but did so between 7.0 and 12
      years younger than in AOMS. CONCLUSIONS: 5.4% of patients with MS have POMS (2.7%
      <16 years; 0.3% <10 years) and have distinct phenotypic characteristics in early
      disease. Furthermore, while patients with POMS take longer to reach disability
      milestones, they do so at a younger age than their adult counterparts and could
      be considered to have a poorer prognosis. Management strategies for these
      patients should take account of these data.

PMID- 23154125
TI  - Deep brain stimulation for dystonia.
AB  - The few controlled studies that have been carried out have shown that bilateral
      internal globus pallidum stimulation is a safe and long-term effective treatment
      for hyperkinetic disorders. However, most recent published data on deep brain
      stimulation (DBS) for dystonia, applied to different targets and patients, are
      still mainly from uncontrolled case reports (especially for secondary dystonia).
      This precludes clear determination of the efficacy of this procedure and the
      choice of the 'good' target for the 'good' patient. We performed a literature
      analysis on DBS for dystonia according to the expected outcome. We separated
      those with good evidence of favourable outcome from those with less predictable
      outcome. In the former group, we review the main results for primary dystonia
      (generalised/focal) and highlight recent data on myoclonus-dystonia and tardive
      dystonia (as they share, with primary dystonia, a marked beneficial effect from
      pallidal stimulation with good risk/benefit ratio). In the latter group, poor or
      variable results have been obtained for secondary dystonia (with a focus on
      heredodegenerative and metabolic disorders). From this overview, the main results
      and limits for each subgroup of patients that may help in the selection of
      dystonic patients who will benefit from DBS are discussed. 

PMID- 23154124
TI  - Verbal memory is associated with structural hippocampal changes in newly
      diagnosed Parkinson's disease.
AB  - BACKGROUND AND OBJECTIVE: Cognitive impairment, including impairment of episodic
      memory, is frequently found in newly diagnosed Parkinson's disease (PD). In this
      longitudinal observational study we investigated whether performance in memory
      encoding, retention, recognition and free recall is associated with reduced
      hippocampal radial distance. METHODS: We analysed baseline T1-weighted brain MRI
      data from 114 PD subjects without cognitive impairment, 29 PD subjects with mild
      cognitive impairment and 99 normal controls from the ParkWest study. Age- and
      education-predicted scores for the California Verbal Learning Test 2 (CVLT-2) and
      tests of executive function were regressed against hippocampal radial distance
      while adjusting for imaging centre. RESULTS: There was no association between
      encoding or performance on executive tests and hippocampal atrophy in the PD
      group. In the full PD sample we found bilaterally significant associations
      between lower delayed free recall scores and hippocampal atrophy in the CA1, CA3
      and subiculum area (left, p=0.0013; right, p=0.0082). CVLT-2 short delay free
      recall scores were associated with bilateral hippocampal CA1 and subicular
      atrophy in the full PD sample (left, p=0.013; right, p=0.047). CVLT-2 recognition
      scores showed a significant association with right-sided subicular and CA1
      atrophy in the full PD sample (p=0.043). CONCLUSIONS: At the time of PD
      diagnosis, subjects' verbal memory performance in recall and recognition are
      associated with atrophy of the hippocampus, while encoding is not associated with
      hippocampal radial distance. We postulate that impaired recall and recognition
      might reflect deficient memory consolidation at least partly due to structural
      hippocampal changes.

PMID- 23154126
TI  - Changes in quality of life scores with intravenous immunoglobulin or
      plasmapheresis in patients with myasthenia gravis.
AB  - BACKGROUND: Intravenous immunoglobulin (IVIG) and plasmapheresis (plasma exchange
      (PLEX)) have comparable efficacy in reducing the Quantitative Myasthenia Gravis
      Score for disease severity (QMGS) in patients with moderate to severe myasthenia
      gravis (MG). OBJECTIVE: To determine if the improvement in the quality of life
      (QOL) after immunomodulation is comparable with either IVIG or PLEX. METHODS: 62
      patients participated in the MG-QOL-60 study, completing the questionnaire at
      baseline and at day 14 after treatment. The MG-QOL-15 scores were computed from
      the MG-QOL-60 questionnaire responses. We analysed the change in the QOL scores
      from baseline to day 14 in both treatment groups. RESULTS: The scores in both QOL
      scales decreased at day 14 in the IVIG and PLEX groups, without significant
      difference between groups (QOL-15: IVIG -5.7 +/- 8.5, PLEX: -7.0 +/- 7.6, p=0.52;
      QOL-60: IVIG -13.3 +/- 16.9, PLEX -18.5 +/- 22.0, p = 0.41). The improvement in
      QOL showed a good correlation with the decrease in QMGS. There was an excellent
      correlation between the MG-QOL-15 and MG-QOL-60 scores at baseline and at day 14.
      CONCLUSIONS: This study of MG-QOL changes supports recent findings that IVIG and
      PLEX are comparable in the treatment of patients with moderate to severe MG and
      worsening symptoms. Furthermore, our study supports the use of the MG-QOL-15 as a
      secondary outcome measure in future clinical trials in MG.

PMID- 23154127
TI  - Modulation of the cellular redox status by the Alternaria toxins alternariol and
      alternariol monomethyl ether.
AB  - The mycotoxin alternariol (AOH) has been reported to possess genotoxic
      properties, inducing enhanced levels of DNA damage after only 1 h of incubation.
      In the present study we addressed the question whether the induction of oxidative
      stress might contribute to the genotoxic effects of AOH or its naturally
      occurring monomethylether (AME). In the dichlorofluorescein (DCF) assay,
      treatment of HT29 cells for 1 h enhanced the formation of dichlorofluorescein,
      indicative for ROS formation. The total glutathione (tGSH) was transiently
      decreased. In accordance with the results of the DCF assay, AOH and AME enhanced
      the proportion of the transcription factor Nrf2 in the nucleus. Concomitantly,
      the Nrf2/ARE-dependent genes gamma-glutamylcysteine ligase (gamma-GCL) and
      glutathione-S-transferase (GSTA1/2) showed enhanced transcript levels. After 24 h
      of incubation this effect was also reflected on the protein level by an increase
      of GST activity. However, in spite of the positive DCF assay and the activation
      of the redox-sensitive Nrf2/ARE-pathway, the level of oxidative DNA damage,
      measured in the comet assay by the addition of formamidopyrimidine-DNA
      glycosylase (fpg) remained unaffected. Of note, after 3 h of incubation no
      significant DNA damaging potential of AOH and AME was detectable, indicating
      either inactivation of the compounds or enhanced DNA repair. In summary, the
      mycotoxins AOH and AME were found to modulate the redox balance of HT29 cells but
      without apparent negative effect on DNA integrity.

PMID- 23154128
TI  - Smooth muscle cells in human atherosclerosis: proteomic profiling reveals
      differences in expression of Annexin A1 and mitochondrial proteins in carotid
      disease.
AB  - Smooth muscle cells (SMC) contribute to the development and stability of
      atherosclerotic lesions. The molecular mechanisms that mediate their properties
      are incompletely defined. We employed proteomics and in vitro functional assays
      to identify the unique characteristics of intimal SMC isolated from human carotid
      endarterectomy specimens and medial SMC from thoracic aortas and carotids. We
      verified our findings in the Tampere Vascular Study. Human atheroma-derived SMC
      exhibit decreased expression of mitochondrial proteins ATP Synthase subunit-beta
      and Aldehyde dehydrogenase 2, and decreased mitochondrial activity when compared
      to control SMC. Moreover, a comparison between plaque-derived SMC isolated from
      patients with or without recent acute cerebrovascular symptoms uncovered an
      increase in Annexin A1, an endogenous anti-inflammatory protein, in the
      asymptomatic group. The deletion of Annexin A1 or the blockade of its signaling
      in SMC resulted in increased cytokine production at baseline and after
      stimulation with the pro-inflammatory cytokine Tumor Necrosis Factor alpha. In
      summary, our proteomics and biochemical analysis revealed mitochondrial damage in
      human plaque-derived SMC as well as a role of Annexin A1 in reducing the
      production of pro-inflammatory mediators in SMC.

PMID- 23154129
TI  - [Sclerosing epithelioid fibrosarcoma of the paravertebral column. Case report and
      literature review].
AB  - Sclerosing epithelioid fibrosarcoma (SEF) is a rare variant of low-grade
      fibrosarcoma, with specific histological and immunohistochemical features and a
      poor prognosis. We report a case of SEF of the paravertebral column in a 49-year
      old male who presented a paraspinal mass with extension into the L4-L5 neural
      foramen and invasion of the L5 nerve root. Histology of the tumourectomy specimen
      and its immunohistochemical study led to the diagnosis of SEF. This case was
      particularly unusual due to its paravertebral column location and, despite its
      low grade, illustrates the malignant potential of SEF. 

PMID- 23154130
TI  - [The history of Spanish neurosurgery: the Valencian school: J.J. Barcia Goyanes].
AB  - Professor Juan Jose Barcia-Goyanes started neurosurgical practice from anatomy
      and neuropsychiatry in response to a vacancy at a department known as "Nervous
      diseases", in 1931 at Hospital General in Valencia, Spain. Since the first
      intervention, based on the methods and surgical instruments already used in
      Europe and the U.S.A., the neurosurgical practice became the mainstay of the
      department, from which other auxiliary specialties emerged, such as
      neuroradiology, neurophysiology, neuropathology and also new techniques such as
      stereotactic surgery, functional neurosurgery and palencephalography. This year,
      the department celebrates its 80th anniversary. The broad spectrum of Prof.
      Barcia's scientific work included fields like neurology, neurosurgery and
      psychiatry, as well as anthropology, medical thought, history of medicine,
      morphology and history of anatomical language in his work "Onomatologica
      anatomica nova", in addition to an interesting poetic work. He was a founding
      member of the Luso-Spanish Neurosurgical Society and the Neurosurgical Society of
      Levante.

PMID- 23154131
TI  - [First intraoperative magnetic resonance imaging in a Spanish hospital of the
      public healthcare system: initial experience, feasibility and difficulties in our
      environment].
AB  - OBJECTIVE: Intraoperative MRI is considered the gold standard among all
      intraoperative imaging technologies currently available. Its main indication is
      in the intraoperative detection of residual disease during tumour resections. We
      present our initial experience with the first intraoperative low-field MRI in a
      Spanish hospital of the public healthcare system. We evaluate its usefulness and
      accuracy to detect residual tumours and compare its intraoperative results with
      images obtained postoperatively using conventional high-field devices. MATERIAL
      AND METHODS: We retrospectively reviewed the first 21 patients operated on the
      aid of this technology. Maximal safe resection was the surgical goal in all
      cases. Surgeries were performed using conventional instrumentation and the
      required assistance in each case. RESULTS: The mean number of intraoperative
      studies was 2.3 per procedure (range: 2 to 4). Intraoperative studies proved that
      the surgical goal had been achieved in 15 patients (71.4%), and detected residual
      tumour in 6 cases (28.5%). After comparing the last intraoperative image and the
      postoperative study, 2 cases (9.5%) were considered as "false negatives".
      CONCLUSIONS: Intraoperative MRI is a safe, reliable and useful tool for guided
      resection of brain tumours. Low-field devices provide images of sufficient
      quality at a lower cost; therefore their universalisation seems feasible.

PMID- 23154132
TI  - Three-step pathway engineering results in more incidence rate and higher emission
      of nerolidol and improved attraction of Diadegma semiclausum.
AB  - The concentration and ratio of terpenoids in the headspace volatile blend of
      plants have a fundamental role in the communication of plants and insects. The
      sesquiterpene (E)-nerolidol is one of the important volatiles with effect on
      beneficial carnivores for biologic pest management in the field. To optimize de
      novo biosynthesis and reliable and uniform emission of (E)-nerolidol, we
      engineered different steps of the (E)-nerolidol biosynthesis pathway in
      Arabidopsis thaliana. Introduction of a mitochondrial nerolidol synthase gene
      mediates de novo emission of (E)-nerolidol and linalool. Co-expression of the
      mitochondrial FPS1 and cytosolic HMGR1 increased the number of emitting
      transgenic plants (incidence rate) and the emission rate of both volatiles. No
      association between the emission rate of transgenic volatiles and their growth
      inhibitory effect could be established. (E)-Nerolidol was to a large extent
      metabolized to non-volatile conjugates.

PMID- 23154133
TI  - How the rehabilitation environment influences patient perception of service
      quality: a qualitative study.
AB  - OBJECTIVE: To identify elements of the environment that patients consider when
      evaluating the quality of a care experience in outpatient rehabilitation
      settings. DESIGN: A qualitative study using a modified grounded theory approach.
      Data collection used semistructured interviewing during 9 focus groups. SETTING:
      Three postacute ambulatory centers in metropolitan areas. PARTICIPANTS: Adults
      (N=57; 33 men, 24 women) undergoing outpatient rehabilitation for musculoskeletal
      conditions/injuries. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Not
      applicable. RESULTS: Participants perceived the quality of rehabilitation service
      on the basis of their experiences with environmental factors, including 3
      physical factors (facility design, ambient conditions, and social factors) and 4
      organizational factors (duration of attendance, interruptions during delivery of
      care, waiting times in the sequence of treatment, and patient safety).
      CONCLUSIONS: This study identifies the specific environmental attributes that
      patients consider important when evaluating the quality of outpatient
      rehabilitation settings and develops a patient-based framework for assessing the
      overall perception of service quality. Further research should work to develop
      self-report questionnaires about patient experiences with the environment in
      rehabilitation services to provide empirical and quantitative evidence.

PMID- 23154134
TI  - Correlation between voluntary cough and laryngeal cough reflex flows in patients
      with traumatic brain injury.
AB  - OBJECTIVE: To correlate voluntary cough and laryngeal cough reflex (LCR) flows in
      patients with traumatic brain injury (TBI). DESIGN: Cross-sectional study.
      SETTING: University rehabilitation hospital. PARTICIPANTS: Patients with TBI
      (n=25) and healthy controls (n=48). INTERVENTIONS: Not applicable. MAIN OUTCOME
      MEASURES: Peak cough flows (PCFs) and LCR flows were measured using a peak flow
      meter at the oral-nasal interface. The largest value of 3 attempts was recorded
      for PCF and LCR, respectively. LCR was elicited by 20% solution of pharmaceutic
      grade citric acid dissolved in sterile .15M NaCl solution that was inhaled from a
      nebulizer. RESULTS: PCF was 447.4 +/- 99.0 L/min in the control group and 211.7
      +/- 58.2 L/min in the patient group. LCR was 209.2 +/- 63.8L/min in the control
      group and 170.0 +/- 59.7 L/min in the patient group. Both PCF (P=.000) and LCR
      (P=.013) were significantly reduced in patients with TBI compared to that of the
      control group. LCR was strongly related to the PCF in both control (R=.645;
      P=.000) and patient (R=.711; P=.000) groups. CONCLUSIONS: As LCR can be measured
      as a numerical value and significantly correlates with PCF, LCR can be used to
      estimate cough ability of patients with TBI who cannot cooperate with PCF
      measurement.

PMID- 23154135
TI  - Joint line tenderness and McMurray tests for the detection of meniscal lesions:
      what is their real diagnostic value?
AB  - OBJECTIVES: To assess the interobserver concordance of the joint line tenderness
      (JLT) and McMurray tests, and to determine their diagnostic efficiency for the
      detection of meniscal lesions. DESIGN: Prospective observational study. SETTING:
      Orthopedics outpatient clinic, university hospital. PARTICIPANTS: Patients (N=60)
      with suspected nonacute meniscal lesions who underwent knee arthroscopy.
      INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Patients were examined by 3
      independent observers with graded levels of experience (>10y, 3y, and 4mo of
      practice). The interobserver concordance was assessed by Cohen-Fleiss kappa
      statistics. Accuracy, negative and positive predictive values for prevalence 10%
      to 90%, positive (LR+) and negative (LR-) likelihood ratios, and the Bayesian
      posttest probability with a positive or negative result were also determined. The
      diagnostic value of the 2 tests combined was assessed by logistic regression.
      Arthroscopy was used as the reference test. RESULTS: No interobserver concordance
      was determined for the JLT. The McMurray test showed higher interobserver
      concordance, which improved when judgments by the less experienced examiner were
      discarded. The whole series studied by the "best" examiner (experienced
      orthopedist) provided the following values: (1) JLT: sensitivity, 62.9%;
      specificity, 50%; LR+, 1.26; LR-, .74; (2) McMurray: sensitivity, 34.3%;
      specificity, 86.4%; LR+, 2.52; LR-, .76. The combination of the 2 tests did not
      offer advantages over the McMurray alone. CONCLUSIONS: The JLT alone is of little
      clinical usefulness. A negative McMurray test does not modify the pretest
      probability of a meniscal lesion, while a positive result has a fair predictive
      value. Hence, in a patient with a suspected meniscal lesion, a positive McMurray
      test indicates that arthroscopy should be performed. In case of a negative
      result, further examinations, including imaging, are needed.

PMID- 23154136
TI  - Electron scattering cross-section measurements in ESEM.
AB  - A review, analysis and discussion on the derivation and measurement of electron
      scattering cross-sections of gases mostly used in environmental scanning electron
      microscopy is presented together with some previously unreported experimental
      material. There are significant differences in values published for cross
      sections of such gases. Scanning the electron beam across a clean edge seems to
      be a most reliable technique to produce and measure beam profiles, from which the
      scattering cross-sections can be obtained with high accuracy and reliability.
      Results based on this method produce an excellent agreement with a theoretically
      derived value of scattering cross-section using an average factor of energy loss
      for all inelastic collisions. The discussion addresses the difficulties involved
      and provides alternative ways to reliably obtain cross-sections as a function of
      accelerating voltage in the range mostly used in environmental scanning electron
      microscopy.

PMID- 23154137
TI  - High cyst concentrations of the potentially toxic dinoflagellate Alexandrium
      tamarense species complex in Bedford Basin, Halifax, Nova Scotia, Canada.
AB  - We report a large cyst bed of the potentially toxic and bloom-forming
      dinoflagellate Alexandrium tamarense species complex in bottom sediments from the
      port of Halifax, Nova Scotia, Canada. The average cyst concentrations of that
      species ranged from 4033+/-2647 to 220872+/-148086 cysts g-1 of dry sediments and
      the highest concentrations were found near ship terminals in Bedford Basin.
      Although this species is endemic to this region, our work strongly suggests that
      some of the cysts of A. tamarense species complex found in the port of Halifax
      were introduced through discharged ballast water and sediments.

PMID- 23154138
TI  - Persistent organic pollutants and stable isotopes in pinnipeds from King George
      Island, Antarctica.
AB  - In the present work, fat, skin, liver and muscle samples from Leptonychotes
      weddellii (Weddell seal, n=2 individuals), Lobodon carcinophagus (crabeater seal,
      n=2), Arctocephalus gazella (Antarctic fur seal, n=3) and Mirounga leonina
      (southern elephant seal, n=1) were collected from King George Island, Antarctica,
      and analysed for POPs (PCBs, organochlorine pesticides and PBDEs) and stable
      isotopes (delta13C and delta15N in all tissues but fat). PBDEs could be found in
      only one sample (L. weddellii fat). Generally, PCBs (from 74 to 523 ng g-1 lw),
      DDTs (from 14 to 168 ng g-1 lw) and chlordanes (from 9 to 78 ng g-1 lw) were the
      prevailing compounds. Results showed a clear stratification in accordance with
      ecological data. Nonetheless, stable isotope analyses provide a deeper insight
      into fluctuations due to migrations and nutritional stress. Correlation between
      delta(15)N and pollutants suggests, to some degree, a considerable ability to
      metabolize and/or excrete the majority of them.

PMID- 23154139
TI  - Urban breakwaters as reef fish habitat in the Persian Gulf.
AB  - Breakwaters and related structures dominate near-shore environments in many
      Persian Gulf countries, but little is known of their ecology. To examine the
      influence of wave exposure on fish communities we surveyed exposed and sheltered
      breakwaters seasonally over 2 years and compared these with natural reef
      assemblages. Species richness and adult, juvenile, and total abundance were
      generally comparable among the three habitat types each season. However,
      differences in multivariate community structure indicated that each habitat
      contained a distinct assemblage, with strongest difference between sheltered
      breakwaters and the exposed natural reef. All communities were characterized by
      marked seasonality; abundance and richness were generally higher in the warmer
      seasons (summer, fall) than during cooler periods (winter, spring), and there
      were related seasonal changes in community structure, particularly on the natural
      reef. Results indicate that breakwaters are important fish habitats, but that
      breakwater communities vary with wave exposure and are distinct from natural
      reefs.

PMID- 23154140
TI  - An integrative method for the evaluation, monitoring, and comparison of seagrass
      habitat structure.
AB  - Assessing environmental condition is essential for the management of coasts and
      their resources, but better management decisions occur when large databases are
      simplified into more manageable units of information. Here we present the habitat
      structure index (HSI), which enables rapid assessment and direct comparison of
      seagrass habitat structure using scores of 0 (poor) to 100 (excellent) based on
      integrating five habitat variables: area, continuity, proximity, percentage
      cover, and species identity. Acquiring data to calculate the HSI can be done in
      situ or from video recordings, and requires relatively simple methodology of belt
      transects, estimating percentage cover, and basic taxonomy. Spatiotemporal
      comparisons can usefully identify locations and periods of seagrass habitat
      change, potentially providing an early warning indicator of habitat damage and
      decline in environmental quality. Overall, the integrative approach of the HSI
      represents a step toward simplifying the exchange of environmental information
      among researchers, coastal managers, and governing bodies.

PMID- 23154141
TI  - Effects of heat stress on development, quality and survival of Bos indicus and
      Bos taurus embryos produced in vitro.
AB  - Heat stress is an important cause of poor development and low survival rates in
      bovine embryos. Experiments were conducted to test the hypothesis that Bos
      indicus embryos are more resistant to heat stress than are Bos taurus embryos. In
      experiment 1, Nelore and Jersey embryos from oocyte pick-up-derived oocytes were
      submitted to heat stress (96 hours post-insemination, 41  degrees C, 6 hours),
      developmental ratios were assessed at Day 7 (Day 0 = day of fertilization), and
      blastocysts were frozen for RNA extraction. Experiment 2 evaluated expression of
      COX2, CDX2, HSF1, and PLAC8 in previously frozen blastocysts. In experiment 3,
      Nellore and Angus embryos from oocyte pick-up-derived oocytes were submitted to
      heat stress (96 hours post-insemination, 41  degrees C, 12 hours) and transferred
      to recipients on Day 7. In experiment 4, embryos developed as in experiment 3
      were fixed for Terminal deoxynucleotidyl transferase dUTP nick end labeling
      labeling and total cell counting. In experiment 1, heat stress decreased the
      percentage of Jersey oocytes that became blastocysts, but had no effect on
      Nellore embryos (34.6%, 25.0%, 39.5%, and 33.0% for Jersey control, Jersey heat
      stressed, Nellore control, and Nellore heat-stressed oocytes, respectively; P <
      0.05). In experiment 2, heat stress decreased (P < 0.05) expression of CDX2 and
      PLAC8, with higher expression of these genes in Nellore embryos than in Jersey
      embryos. Heat stress also decreased (P < 0.05) expression of COX2 in Jersey
      embryos, but had no effect on Nellore embryos. Expression of HSF1 was decreased
      (P < 0.05) by heat stress in both breeds, with a greater effect in Nellore
      embryos. In experiment 3, heat stress tended (P = 0.1) to decrease the percentage
      of pregnancies among cows (Day 30 to 35) that received Angus embryos. In
      experiment 4, heat stress increased (P < 0.05) the percentage of apoptotic
      blastomeres, but had no breed-specific effects. In addition, Nellore embryos had
      fewer (P < 0.05) Terminal deoxynucleotidyl transferase dUTP nick end labeling-
      positive blastomeres than did Angus embryos. We concluded that the detrimental
      effects of heat stress were dependent upon embryo breed and were more evident in
      Bos taurus embryos than in Bos indicus embryos.

PMID- 23154142
TI  - Ovarian response and embryo gene expression patterns after nonsuperovulatory
      gonadotropin stimulation in primiparous rabbits does.
AB  - Ovarian stimulation with equine chorionic gonadotropin (eCG) is largely used in
      animal reproductive technologies to provide a larger number of oocytes and
      embryos and to improve the reproductive outcome. However, the consequences of
      maternal treatment with eCG on embryo gene expression patterns are not widely
      studied. The aim of this work was to assess the ovarian response (preovulatory
      follicular population, oocyte maturation, ovulation rate, and serum steroid
      concentrations), the early embryo survival and gene expression patterns of a
      panel of quality-genes involved in glucose intake, oxidative stress, apoptosis,
      proliferation, implantation, and fetal growth in embryos of lactating rabbits
      treated with eCG. A total of 34 primiparous rabbit does (Oryctolagus cuniculus)
      were randomly distributed at Day 23 postpartum into a treatment group receiving a
      unique nonsuperovulatory dose (25 IU) of eCG (eCG group; N = 17 does); or a
      control group without eCG treatment previously to artificial insemination
      (control group; N = 17 does). After 48 hours, 8 does of each group were
      euthanized and their ovarian response was studied. The rest of animals were
      artificially inseminated and their ovulation was induced with a GnRH analogue.
      Embryos were recovered 3.5 days later. The oocytes retrieved for in vitro
      maturation showed no differences in metaphase II rate in both experimental
      groups, although oocyte cytoplasmic maturation, in terms of cortical granule
      migration rate, was improved in eCG-treated does (P < 0.05). The mean number of
      preovulatory follicles was similar between groups but the ovulation rate was
      significantly higher in eCG-treated does compared with does not stimulated (P <
      0.05). No differences were found in serum estradiol and progesterone
      concentrations of does the day of oocyte and embryo recovery, respectively.
      However, progesterone:estradiol ratio was slightly increased in eCG group on
      embryo recovery day (P = 0.1). The percentage of embryos recovered at the
      blastocyst stage was also increased in eCG-treated does (P < 0.05), nevertheless,
      there were no differences in the gene expression patterns of candidate genes
      SLC2A4, IGF1R, IGF2R, SHC1-SHC, TP53, PTGS2, and PLAC8; except for the
      transcripts of SOD1 mRNA which were downregulated in eCG-derived embryos (P <
      0.05). In conclusion, the administration of eCG improves ovulation rate, oocyte
      cytoplasmic maturation, and blastocyst formation in primiparous rabbit does
      inseminated on Day 25 postpartum. Although it seems not to influence the gene
      expression patterns studied, a lower antioxidant defense of embryos developed
      after the maternal eCG treatment is suggested.

PMID- 23154143
TI  - Differential gene expressions in testes of L2 strain Taiwan country chicken in
      response to acute heat stress.
AB  - Acute heat stress affects genes involved in spermatogenesis in mammals. However,
      there is apparently no elaborate research on the effects of acute heat stress on
      gene expression in avian testes. The purpose of this study was to investigate
      global gene expression in testes of the L2 strain of Taiwan country chicken after
      acute heat stress. Twelve roosters, 45 weeks old, were allocated into four
      groups, including control roosters kept at 25  degrees C, roosters subjected to
      38  degrees C acute heat stress for 4 hours without recovery, with 2-hour
      recovery, and with 6-hour recovery, respectively. Testis samples were collected
      for RNA isolation and microarray analysis. Based on gene expression profiles, 169
      genes were upregulated and 140 genes were downregulated after heat stress using a
      cutoff value of twofold or greater change. Based on gene ontology analysis,
      differentially expressed genes were mainly related to response to stress,
      transport, signal transduction, and metabolism. A functional network analysis
      displayed that heat shock protein genes and related chaperones were the major
      upregulated groups in chicken testes after acute heat stress. A quantitative real
      time polymerase chain reaction analysis of mRNA expressions of HSP70, HSP90AA1,
      BAG3, SERPINB2, HSP25, DNAJA4, CYP3A80, CIRBP, and TAGLN confirmed the results of
      the microarray analysis. Because the HSP genes (HSP25, HSP70, and HSP90AA1) and
      the antiapoptotic BAG3 gene were dramatically altered in heat-stressed chicken
      testes, we concluded that these genes were important factors in the avian testes
      under acute heat stress. Whether these genes could be candidate genes for
      thermotolerance in roosters requires further investigation.

PMID- 23154145
TI  - Why do singletons conceived after assisted reproduction technology have adverse
      perinatal outcome? Systematic review and meta-analysis.
AB  - BACKGROUND: Assisted reproduction technology (ART) is used worldwide, at
      increasing rates, and data show that some adverse outcomes occur more frequently
      than following spontaneous conception (SC). Possible explanatory factors for the
      well-known adverse perinatal outcome in ART singletons were evaluated. METHODS:
      PubMed and Cochrane databases from 1982 to 2012 were searched. Studies using
      donor or frozen oocytes were excluded, as well as those with no control group or
      including <100 children. The main outcome measure was preterm birth (PTB defined
      as delivery <37 weeks of gestation), and a random effects model was used for meta
      analyses of PTB. Other outcomes were very PTB, low-birthweight (LBW), very LBW,
      small for gestational age and perinatal mortality. RESULTS: The search returned
      1255 articles and 65 of these met the inclusion criteria. The following were
      identified as predictors for PTB in singletons: SC in couples with time to
      pregnancy (TTP) > 1 year versus SC singletons in couples with TTP <= 1 year
      [adjusted odds ratio (AOR) 1.35, 95% confidence interval (CI) 1.22, 1.50];
      IVF/ICSI versus SC singletons from subfertile couples (TTP > 1 year; AOR 1.55,
      95% CI 1.30, 1.85); conception after ovulation induction and/or intrauterine
      insemination versus SC singletons where TTP <= 1 year (AOR 1.45, 95% CI 1.21,
      1.74); IVF/ICSI singletons versus their non-ART singleton siblings (AOR 1.27, 95%
      CI 1.08, 1.49). The risk of PTB in singletons with a 'vanishing co-twin' versus
      from a single gestation was AOR of 1.73 (95% CI 1.54, 1.94) in the narrative
      data. ICSI versus IVF (AOR 0.80, 95% CI 0.69-0.93), and frozen embryo transfer
      versus fresh embryo transfer (AOR 0.85, 95% CI 0.76, 0.94) were associated with a
      lower risk of PTB. CONCLUSIONS: Subfertility is a major risk factor for adverse
      perinatal outcome in ART singletons, however, even in the same mother an ART
      singleton has a poorer outcome than the non-ART sibling; hence, factors related
      to the hormone stimulation and/or IVF methods per se also may play a part.
      Further research is required into mechanisms of epigenetic modification in human
      embryos and the effects of cryopreservation on this, whether milder ovarian
      stimulation regimens can improve embryo quality and endometrial conditions, and
      whether longer culture times for embryos has a negative influence on the
      perinatal outcome.

PMID- 23154144
TI  - Equine chorionic gonadotropin improves the efficacy of a timed artificial
      insemination protocol in buffalo during the nonbreeding season.
AB  - Two experiments were conducted to evaluate the effects of equine chorionic
      gonadotropin (eCG) treatment on ovarian follicular response, luteal function, and
      pregnancy in buffaloes subjected to a timed artificial insemination (TAI)
      protocol during the nonbreeding season. In experiment 1, 59 buffalo cows were
      randomly assigned to two groups (with and without eCG). On the first day of the
      synchronization protocol (Day 0), cows received an intravaginal progesterone (P4)
      device plus 2.0 mg estradiol benzoate im. On Day 9, the P4 device was removed,
      all cows were given 0.150 mg PGF(2alpha) im, and half were given 400 IU eCG im.
      On Day 11, all cows were given 10 MUg of buserelin acetate im (GnRH). Transrectal
      ultrasonography of the ovaries was performed on Days 0 and 9 to determine the
      presence and diameter of the largest follicle; between Days 11 and 14 (12 hours
      apart), to evaluate the dominant follicle diameter and the interval from device
      removal to ovulation; and on Days 16, 20, and 24 to measure CL diameter. Blood
      samples were collected on Days 16, 20, and 24 to measure serum P4. In experiment
      2, 256 buffaloes were assigned to the same treatments described in experiment 1,
      and TAI was performed 16 hours after GnRH treatment. Pregnancy diagnosis was
      performed by ultrasonography 30 days after TAI. Treatment with eCG increased the
      maximum diameter of dominant follicles (P = 0.09), ovulation rate (P = 0.05), CL
      diameter (P = 0.03), and P4 concentrations (P = 0.01) 4 days after TAI, and
      pregnancy per AI (52.7%, 68/129 vs. 39.4%, 50/127; P = 0.03). Therefore, eCG
      improved ovarian follicular response, luteal function during the subsequent
      diestrus, and fertility for buffalo subjected to a TAI synchronization protocol
      during the nonbreeding season.

PMID- 23154146
TI  - Toward a non-invasive screening tool for differentiation of pancreatic lesions
      based on intra-voxel incoherent motion derived parameters.
AB  - Early recognition of and differential diagnosis between pancreatic cancer and
      chronic pancreatitis is an important step in successful therapy. Parameters of
      the IVIM (intra-voxel incoherent motion) theory can be used to differentiate
      between those lesions. The objective of this work is to evaluate the effects of
      rigid image registration on IVIM derived parameters for differentiation of
      pancreatic lesions such as pancreatic cancer and solid mass forming pancreatitis.
      The effects of linear image registration methods on reproducibility and accuracy
      of IVIM derived parameters were quantified on MR images of ten volunteers. For
      this purpose, they were evaluated statistically by comparison of registered and
      unregistered parameter data. Further, the perfusion fraction f was used to
      differentiate pancreatic lesions on eleven previously diagnosed patient data
      sets. Its diagnostic power with and without rigid registration was evaluated
      using receiver operating curves (ROC) analysis. The pancreas was segmented
      manually on MR data sets of healthy volunteers as well as the patients showing
      solid pancreatic lesions. Diffusion weighted imaging was performed in 10 blocks
      of breath-hold phases. Linear registration of the weighted image stack leads to a
      3.7% decrease in variability of the IVIM derived parameter f due to an improved
      anatomical overlap of 5%. Consequently, after registration the area under the
      curve in the ROC-analysis for the differentiation approach increased by 2.7%. In
      conclusion, rigid registration improves the differentiation process based on f
      values.

PMID- 23154147
TI  - Curricular disconnects in learning communication skills: what and how students
      learn about communication during clinical clerkships.
AB  - OBJECTIVE: In many medical schools, formal training in clinical communication
      skills (CCS) mainly occurs during pre-clinical training prior to clinical
      rotations. The current research examined student perceptions of both what and how
      they learn about CCS during clinical rotations. METHODS: During 2008 and 2009,
      4th year medical students were invited to participate in interviews focused on
      learning of CCS during clinical rotations. Interview transcripts were analyzed to
      identify salient themes in their discussions of CCS in clinical learning
      experiences. RESULTS: 107 senior students participated and reported learning CCS
      during clinical rotations mainly by: (1) observing faculty and residents; (2)
      conducting interviews themselves; and (3) through feedback on patient
      presentations. Teacher role modeling tended to not reinforce what they had
      learned pre-clinically about CCS and clinical teachers rarely discussed CCS.
      Feedback on patient presentations affected students' communication styles, at
      times prompting them to omit use of CCS they had learned pre-clinically.
      CONCLUSIONS: Students reported that clinical learning experiences often do not
      reinforce the CCS they learn pre-clinically. PRACTICAL IMPLICATIONS: Disconnects
      between pre-clinical and clinical CCS teaching need to be reconciled through more
      explicit pedagogical attention to CCS issues during clinical rotations both in
      the formal and informal curriculum.

PMID- 23154148
TI  - Time to sign: The relationship between health literacy and signature time.
AB  - OBJECTIVE: To evaluate the relationship between amount of time taken to sign
      one's name and health literacy. METHODS: A prospective, one time assessment was
      conducted on a convenience sample of 98 patients recruited in an inner-city
      outpatient internal medicine clinic. The amount of time required to sign (i.e.
      initiation to completion of writing) was measured by stopwatch. Health literacy
      was measured with the REALM. RESULTS: The sample averaged 54.1 (SD 16.2) years of
      age. Twenty-seven percent had less than high school education and 33% had a
      terminal general equivalency diploma or high school degree. The time required to
      sign ranged from 0.91 to 21.3s. Sixty-two percent of the sample had health
      literacy challenges. Signature time was longest for those with inadequate health
      literacy (mean 10.0 s), compared with marginal (7.3s) and adequate (4.7s, p <=
      0.001). Signature time remained significant in a logistic regression model after
      controlling for education and age (AOR = 0.785, CI = 0.661-0.932). CONCLUSION:
      Individuals with signatures completed in six seconds or less were highly likely
      to display adequate health literacy. PRACTICE IMPLICATIONS: Signature time may
      offer a practical and quick approach to health literacy screening in the health
      care setting.

PMID- 23154149
TI  - The evolution of midwifery education at the master's level: a study of Swedish
      midwifery education programmes after the implementation of the Bologna process.
AB  - In Europe, midwifery education has undergone a number of reforms in the past few
      decades. In several countries, it has shifted from vocational training to
      academic education. The higher education reform, known as the "Bologna process"
      aimed to create convergence in higher education among a number of European
      countries and enhance opportunities for mobility, employment and collaborative
      research. It also indicated a transparent and easily compared system of academic
      degrees, generating a new educational system in three cycles. This study explores
      the implementation of the process in Sweden when the midwifery education was
      transferred from diploma to postgraduate or master's level. The aim of this study
      was to analyse how the implementation of the Bologna process in the Swedish
      higher education system has impacted midwifery education programmes in the
      country. Descriptive statistics and content analysis were employed to analyse 32
      questionnaire responses from teachers and the 2009-2010 curricula and syllabi of
      11 postgraduate midwifery education programmes at Swedish universities and
      university colleges. The results revealed variations among the universities at
      the major subject into the three disciplines; midwifery, nursing and caring with
      different conceptualisations, even when the content was identical in the
      curricula to that of the midwifery professional knowledge base. Implementation of
      the new reform not only has accelerated the academisation process, but also puts
      higher demand on the students and requires higher competencies among teachers to
      involve more evidence-based knowledge, seminars, independent studies and a
      postgraduate degree project in the major subject. Thus the students earn not only
      a diploma in midwifery, but also a master's degree in the major subject, which
      affords the opportunity for an academic career. But still there is a tension
      between professional and academic education. 

PMID- 23154150
TI  - Understanding and improving patient experience: a national survey of training
      courses provided by higher education providers and healthcare organizations in
      England.
AB  - BACKGROUND: Understanding and improving 'patient experience' is essential to
      delivering high quality healthcare. However, little is known about the provision
      of education and training to healthcare staff in this increasingly important
      area. OBJECTIVES: This study aims to ascertain the extent and nature of such
      provision in England and to identify how it might be developed in the future.
      METHODS: An on-line survey was designed to explore training provision relating to
      patient experiences. To ensure that respondents thought about patient experience
      in the same way we defined patient experience training as that which aims to
      teach staff: 'How to measure or monitor the experience, preferences and
      priorities of patients and use that knowledge to improve their experience'.
      Survey questions (n=15) were devised to cover nine consistently reported key
      aspects of patient experience; identified from the research literature and
      recommendations put forward by professional bodies. The survey was administered
      to (i) all 180 providers of Higher Education (HE) to student/qualified doctors,
      nurses and allied health professionals, and (ii) all 390 National Health Service
      (NHS) trusts in England. In addition, we added a single question to the NHS 2010
      Staff Survey (n=306,000) relating to the training staff had received to deliver a
      good patient experience. RESULTS: Two hundred and sixty-five individuals
      responded to the on-line survey representing a total of 159 different
      organizations from the HE and healthcare sectors. Respondents most commonly
      identified 'relationships' as an 'essential' aspect of patient experience
      education and training. The biggest perceived gaps in current provision related
      to the 'physical' and 'measurement' aspects of our conceptualization of patient
      experience. Of the 148,657 staff who responded to the Staff Survey 41% said they
      had not received patient experience training and 22% said it was not applicable
      to them. CONCLUSIONS: While some relevant education courses are in place in
      England, the results suggest that specific training with regard to the physical
      needs and comfort of patients, and how patient experiences can be measured and
      used to improve services, should be introduced. Future developments should also
      focus, firstly, on involving a wider range of patients in planning and delivering
      courses and, secondly, evaluating whether courses impact on the attitudes and
      behaviors of different professional groups and might therefore contribute to
      improved patient experiences.

PMID- 23154151
TI  - Alcohol education and training in pre-registration nursing: a national survey to
      determine curriculum content in the United Kingdom (UK).
AB  - BACKGROUND: Alcohol-related harm impacts significantly on the health of the
      population. Nurses are often among the first health professionals that many
      patients with alcohol-related problems come into contact with and have been
      identified as playing a key role but may be ill-prepared to respond. Future
      nurses need to have the skills, knowledge and clinical confidence to respond to
      patients suffering from alcohol-related harm. A pre-registration curriculum that
      ensures a nursing workforce fit for practice in responding to alcohol-related
      harm is necessary. OBJECTIVES: To determine the level of alcohol education and
      training content in the pre-registration curriculum for nursing in the United
      Kingdom (UK). To establish whether there are variations in the pre-registration
      curriculum content across the UK. DESIGN: A descriptive study. SETTING: All 68 UK
      Higher Education Institutions offering a total of 111 pre-registration courses
      for nurses were invited to participate in the study. PARTICIPANTS: Twenty nine
      completed questionnaires were returned, a response rate of 26%. The largest
      number of identified responders were from England (n=15), with 3 from Scotland
      and 1 each from Wales and Northern Ireland. Nine Universities chose not to
      identify themselves. METHODS: An online semi-structured questionnaire survey was
      used to collect the study data. RESULTS: Teaching of alcohol and alcohol related
      harm was mainly delivered during the second year of a pre-registration nursing
      programme provided mainly to adult and mental health students. Overall, the
      majority of alcohol related content that is provided within the responding pre
      registration nursing courses relates to biophysiology, aetiology, and
      pharmacological and non-pharmacological interventions. CONCLUSION: This study
      highlights the need for a greater and more relevant focus of alcohol education to
      pre-registration nursing students of all fields of practice incorporating an
      integrated approach across all years of study.

PMID- 23154152
TI  - Preparation and characterization of CK2 inhibitor-loaded cyclodextrin
      nanoparticles for drug delivery.
AB  - Casein Kinase 2 (CK2) is a ubiquitous kinase protein currently targeted for the
      treatment of some cancers. Recently, the series of indeno[1,2-b]indoles has
      revealed great interest as potent and selective CK(2) ATP-competitive inhibitors.
      Among them, 1-amino-5-isopropyl-5,6,7,8-tetrahydroindeno[1,2-b]indole-9,10-dione
      (CM1) was selected for an encapsulation study in order to improve its
      biodisponibility. Its complexation was evaluated at the molecular scale, with a
      series of fluorinated or hydrocarbonated amphiphilic cyclodextrins (CDs). Then
      the encapsulation of CM1 within CD nanoparticles at the supramolecular level was
      achieved. Nanoparticles formed between CM1 and hexakis[6-deoxy-6-(3
      perfluorohexylpropanethio)-2,3-di-O-methyl]-alpha-cyclodextrin, a fluorinated
      amphiphilic alpha-cyclodextrin, gave the best results in terms of encapsulation
      rate, stability and drug release. These nanospheres showed an encapsulation
      efficiency of 65% and a sustained release of the entrapped drug over 3h. Based on
      these results, encapsulation within fluorinated amphiphilic CD nanoparticles
      could be considered as a potential drug delivery system for indenoindole-type CK2
      inhibitors, allowing better biodisponibility and offering perspectives for tumor
      targeting development.

PMID- 23154153
TI  - 21st-century alternatives to classic resurfacing techniques.

PMID- 23154154
TI  - Subcutaneous pedicled V-Y advancement flap for surgical reconstruction of the
      auricle of the ear.
AB  - The subcutaneous pedicled V-Y advancement flap is useful for the repair of small
      and medium-sized defects in areas where it is easy to obtain a good subcutaneous
      pedicle (upper lip, cheek, eyebrow, and nasal tip and ala). The almost complete
      absence of subcutaneous tissue on the anterior aspect of the auricle of the ear
      can limit the use of this approach in this region. We present 4 patients in whom
      subcutaneous pedicled V-Y advancement flaps were used to repair surgical defects
      of the helix, scaphoid fossa, and antitragus, achieving a good functional and
      aesthetic result in all cases. 

PMID- 23154155
TI  - High versus low glycemic index 3-h recovery diets following glycogen-depleting
      exercise has no effect on subsequent 5-km cycling time trial performance.
AB  - OBJECTIVES: Some athletes train/compete multiple times in a single day and rapid
      restoration of muscle and hepatic glycogen stores is therefore important for
      athletic performance. DESIGN: Randomised, counterbalanced, crossover, single
      blinded study investigated the effects of low/high glycaemic index (GI) meals on
      the physiological responses to a 3-h recovery period and subsequent 5-km cycling
      time trial (TT). METHODS: Seven male cyclists completed glycogen-depleting
      exercise followed by a 3-h recovery period, when participants consumed either a
      high or low GI meal providing 2gkg(-1) BM of carbohydrate. Participants then
      performed a 5-km cycling TT. Blood samples were analysed for glucose insulin,
      free fatty acid (FFA) and triglyceride. RESULTS: There was no significant
      difference between the median (IQR) cycling TT time of 8.5 (3.0) min in the LGI
      condition and 8.4 (1.8) min in the HGI condition (p=0.45). Serum insulin was
      significantly higher in the HGI condition throughout the 3-h recovery period
      (p=0.025), FFA concentrations were higher in the HGI condition only at 30min into
      recovery (p=0.008). The respiratory exchange ratio (p=0.028) and carbohydrate
      oxidation rate (p=0.015) increased over time in the HGI condition, whereas the
      rate of fat oxidation demonstrated the opposite response (p=0.001). No
      significant differences between conditions were observed for any physiological
      variables at the end of the 5-km TT. CONCLUSIONS: Although the GI of the two
      meals indicated important metabolic differences during the recovery period, there
      was no evidence suggesting these differences influenced subsequent 5-km TT
      performance.

PMID- 23154156
TI  - For non-exercising people, the number of steps walked is more strongly associated
      with health than time spent walking.
AB  - OBJECTIVE: This study examined the associations between walking (number of steps
      and minutes spent) and seven health indicators, including chronic health
      conditions, depressive symptoms, and blood pressure, among nonexercising people
      who did not regularly engage in any non-walking moderate-to-vigorous physical
      activity in Hong Kong. DESIGN: Under the FAMILY project, the number of steps per
      day and minutes spent walking were measured using an accelerometer. Participants
      (n=2417) whose only form of physical activity was walking were included in the
      present analysis. METHODS: Three indicators of walking (number of steps, minutes
      spent walking at moderate intensity, and minutes spent walking at light
      intensity) was measured by accelerometer. Associations between these indicators
      and seven health conditions were measured by the difference in z scores for those
      with, and those without, each health condition, adjusted for age and sex.
      RESULTS: The number of steps per day was significantly and inversely associated
      with hypertension (difference in z=-0.22, p<0.01), cancer (difference in z=-0.43,
      p<0.05), stroke (difference in z=-0.63, p<0.01), depressive symptoms (difference
      in z=-0.15, p<0.01), health-related quality-of-life (difference in z=-0.13,
      p<0.05), and pulse rate (difference in z=-0.11, p<0.01). By contrast, time spent
      walking as measured by accelerometer was associated only with a single health
      indicator (hypertension, difference in z=-0.14, p<0.05). CONCLUSIONS: Even among
      non-exercising people, accumulating number of steps appears to be related to
      fewer health problems and should be promoted as an accessible form of exercise,
      especially for those who lack the time or ability to engage in physical activity
      of at least moderate intensity.

PMID- 23154157
TI  - African swine fever virus controls the host transcription and cellular machinery
      of protein synthesis.
AB  - Throughout a viral infection, the infected cell reprograms the gene expression
      pattern in order to establish a satisfactory antiviral response. African swine
      fever virus (ASFV), like other complex DNA viruses, sets up a number of
      strategies to evade the host's defense systems, such as apoptosis, inflammation
      and immune responses. The capability of the virus to persist in its natural hosts
      and in domestic pigs, which recover from infection with less virulent isolates,
      suggests that the virus displays effective mechanisms to escape host defense
      systems. ASFV has been described to regulate the activation of several
      transcription factors, thus regulating the activation of specific target genes
      during ASFV infection. Whereas some reports have concerned about anti-apoptotic
      ASFV genes and the molecular mechanisms by which ASFV interferes with inducible
      gene transcription and immune evasion, less is yet known regarding how ASFV
      regulates the translational machinery in infected cells, although a recent report
      has shown a mechanism for favored expression of viral genes based on
      compartmentalization of viral mRNA and ribosomes with cellular translation
      factors within the virus factory. The viral mechanisms involved both in the
      regulation of host genes transcription and in the control of cellular protein
      synthesis are summarized in this review.

PMID- 23154158
TI  - Newborn screening for congenital hypothyroidism.
AB  - Newborn screening (NS) for congenital hypothyroidism (CH) is one of the major
      achievements in preventive medicine. Most neonates born with CH have normal
      appearance and no detectable physical signs. Hypothyroidism in the newborn period
      is almost always overlooked, and delayed diagnosis leads to the most severe
      outcome of CH, mental retardation, emphasizing the importance of NS. Blood spot
      thyroid stimulating hormone (TSH) or thyroxine (T4) or both can be used for CH
      screening. The latter is more sensitive but not cost-effective, so screening by
      TSH or T4 is used in different programs around the world. TSH screening was shown
      to be more specific in the diagnosis of CH. T4 screening is more sensitive in
      detecting especially those newborns with rare hypothalamic-pituitary
      hypothyroidism, but it is less specific with a high frequency of false positives
      mainly in low birth weight and premature infants. The time at which the sample is
      taken may vary. In the majority of the centers, blood is obtained from a heel
      prick after 24 hours of age to minimize the false positive high TSH due to the
      physiological neonatal TSH surge that elevates TSH levels and causes dynamic T4
      and T3 changes in the first 1 or 2 days after birth. Early discharge of mothers
      postpartum has increased the ratio of false positive TSH elevations. Although
      transient hypothyroidism may occur frequently, all these infants should be
      treated as having CH for the first 3 years of life, taking into account the risk
      of mental retardation. A reevaluation after 3 years is needed in such patients.
      The goal of initial therapy in CH is to minimize neonatal central nervous system
      exposure to hypothyroidism by normalizing thyroid function, as rapidly as
      possible.

PMID- 23154159
TI  - Subclinical hypothyroidism in children: natural history and when to treat.
AB  - Subclinical hypothyroidism (SH) is a quite common disorder in the pediatric age
      group. The aim of this paper is to present a review of the studies investigating
      the natural course of SH and the effects of replacement therapy with
      levothyroxine in childhood. We systematically searched PubMed, Cochrane, and
      EMBASE (1990 to 2012) and identified 14 articles suitable to be included. SH is a
      benign process that does not influence anthropometric parameters or puberty
      onset, and in most cases, it is a remitting disease, with a low risk of
      development of overt hypothyroidism, more frequently evolving toward euthyroidism
      or steadily remaining in a condition of isolated hyperthyrotropinemia.Studies
      analyzing the effects of replacement therapy in SH have reported an increased
      growth velocity in children with short stature or chronic diseases, discordant
      effects on thyroid volume reduction, and no effects on neurocognitive function.
      SH in children and adolescent is often a self-remitting process and its treatment
      should be considered only when thyroid stimulating hormone values are higher than
      10 mIU/L,when clinical signs or symptoms of impaired thyroid function or goiter
      are detected, or when SH is associated with other chronic diseases.

PMID- 23154161
TI  - Hyperthyroidism in childhood: causes, when and how to treat.
AB  - Graves' disease (GD) is the most common cause of hyperthyroidism in children.
      This review gives an overview and update of management of GD. Antithyroid drugs
      (ATD) are recommended as the initial treatment, but the major problem is the high
      relapse rate (30%) as remission is achieved after a first course of ATD. More
      prolonged medical treatment may increase the remission rate up to 50%.
      Alternative treatments, such as radioactive iodine or thyroidectomy, are
      considered in cases of relapse, lack of compliance, or ATD toxicity. Therefore,
      clinicians have sought prognostic indicators of remission. Relapse risk decreases
      with longer duration of the first course of ATD treatment, highlighting the
      positive impact of a long period of primary ATD treatment on outcome. The
      identification of other predictive factors such as severe biochemical
      hyperthyroidism at diagnosis, young age, and absence of other autoimmune
      conditions has made it possible to stratify patients according to the risk of
      relapse after ATD treatment, leading to improvement in patient management by
      facilitating the identification of patients requiring long-term ATD or early
      alternative therapy. Neonatal autoimmune hyperthyroidism is generally transient,
      occurring in only about 2% of the offspring of mothers with GD. Cardiac
      insufficiency, intrauterine growth retardation, craniostenosis, microcephaly and
      psychomotor disabilities are the major risks in these infants and highlight the
      importance of thyroid hormone receptor antibody determination throughout
      pregnancy in women with GD, as well as highlighting the need for early diagnosis
      and treatment of hyperthyroidism.

PMID- 23154162
TI  - Current loss-of-function mutations in the thyrotropin receptor gene: when to
      investigate, clinical effects, and treatment.
AB  - Thyroid-stimulating hormone receptor (TSHR) loss-of-function (LOF) mutations lead
      to a wide spectrum of phenotypes, ranging from severe congenital hypothyroidism
      (CH) to mild euthyroid hyperthyrotropinemia. The degree of TSH resistance depends
      on the severity of the impairment of the receptor function caused by the mutation
      and on the number of mutated alleles In this review data about genotype-phenotype
      correlation and criteria for clinical work-up will be presented and discussed.
      Complete TSH resistance due to biallelic LOF TSHR mutations must be suspected in
      all patients with severe not syndromic CH and severe thyroid hypoplasia diagnosed
      at birth by neonatal screening. Partial forms of TSH resistance show a more
      heterogeneous hormonal and clinical pattern . In these cases TSH serum levels are
      above the upper limit of normal range for the age but with a very variable
      pattern, free thyroxine (T4) concentrations are within the normal range and
      thyroid size can be normal or hypoplastic at ultrasound scan. An early
      substitutive treatment with L-T4 must be mandatory in all patients with severe CH
      due to complete uncompensated TSH resistance diagnosed at birth by neonatal
      screening. The usefulness of substitutive treatment appears much more
      controversial inpatients with subclinical hypothyroidism due to partial TSH
      resistance in whom the increased TSH concentration should be able to compensate
      the mild functional impairment of the mutant receptor. Together with standard
      criteria we recommend also an accurate clinical work-up to select patients who
      are candidates for a LOF TSHR mutation.

PMID- 23154163
TI  - Optimising outcome in congenital hypothyroidism; current opinions on best
      practice in initial assessment and subsequent management.
AB  - Congenital hypothyroidism (CH), usually of the primary and permanent variety, is
      an eminently preventable cause of growth retardation and mental handicap whose
      outlook has been transformed by newborn screening, usually involving the
      measurement of capillary thyroid stimulating hormone (TSH). Severe primary CH,
      due for example to athyreosis, may result in subtle cognitive, behavioural and
      sensori-motor deficits, but the extent to which these can be offset by optimal
      postnatal diagnosis and management remains uncertain. This is because the
      available adult follow-up data reflect the outcome of previous management in the
      1970's and 1980's, and also because the accurate neuro-psychological assessment
      of children is difficult, particularly in the preschool population. There is an
      urgent need to develop new consensus guidelines and to ensure that the children
      managed according to such guidelines are systematically and prospectively
      assessed so that good quality outcome data become available. In this review, key
      recommendations in the management of CH include: screening at day 3 so that
      severely affected infants can begin treatment within the first 10 days of life;
      setting the TSH referral cut-off at 8-10 mU/L; adopting a disciplined diagnostic
      algorithm to evaluate referred cases, with measurement of venous free thyroxine
      (T4), TSH and thyroglobulin combined with dual ultrasound and radioisotope
      imaging; initial treatment with a T4 dose of 50 MUg daily in infants weighing >=
      2.5 kg and 15 MUg/kg/day in infants weighing < 2.5 kg followed by weekly review
      until thyroid function is normalised; and maintenance of free T4 levels between
      15-26 pmol/L and TSH between 0.5-5 mU/L thereafter to avoid both under- and
      overtreatment.

PMID- 23154164
TI  - Autoimmune thyroiditis in childhood.
AB  - Autoimmune thyroiditis (AIT) is the most common thyroid disorder in the pediatric
      age range. The disease results from an as yet poorly characterized defect or
      defects in immunoregulation and a cascade of events progressing from lymphocyte
      infiltration of the thyroid, to T-cell- and cytokine-mediated thyroid follicular
      cell injury, and apoptotic cell death. Approximately 70% of disease risk has been
      attributed to genetic background with environmental factors being important in
      triggering disease in susceptible individuals. The contribution of individual
      genes is small and probably polymorphisms in multiple genes play a role. Some
      immuno susceptibility genes affect immune recognition or response in general,
      while others are thyroid-specific. Environmental agents may act through an
      epigenetic mechanism. Antibodies (Abs) to a variety of thyroid-specific antigens
      are detectable in a majority of patients, but the role of Abs in mediating cell
      injury and death is unclear and only thyrotropin (TSH) receptor Abs significantly
      affect thyroid function by interfering with (or stimulating) the action of TSH.
      Nonetheless, thyroid peroxidase (TPO) Abs and thyroglobulin (Tg) Abs, present in
      a majority of patients, are valuable diagnostically as markers of underlying
      autoimmune thyroid destruction. TSH receptor blocking Abs are found in ~18% of
      children and adolescents with severe hypothyroidism and, when persistent, may
      identify an adolescent likely to have a baby with TSH receptor blocking Ab
      induced congenital hypothyroidism. AIT may coexist with other organ-specific
      autoimmune diseases. Although the most common age at presentation is adolescence,
      the disease may occur rarely in children <1 year of life.

PMID- 23154165
TI  - C-terminal turn stability determines assembly differences between Abeta40 and
      Abeta42.
AB  - Oligomerization of the amyloid beta-protein (Abeta) is a seminal event in
      Alzheimer's disease. Abeta42, which is only two amino acids longer than Abeta40,
      is particularly pathogenic. Why this is so has not been elucidated fully. We
      report here results of computational and experimental studies revealing a C
      terminal turn at Val36-Gly37 in Abeta42 that is not present in Abeta40. The
      dihedral angles of residues 36 and 37 in an Ile31-Ala42 peptide were consistent
      with beta-turns, and a beta-hairpin-like structure was indeed observed that was
      stabilized by hydrogen bonds and by hydrophobic interactions between residues 31
      35 and residues 38-42. In contrast, Abeta(31-40) mainly existed as a statistical
      coil. To study the system experimentally, we chemically synthesized Abeta
      peptides containing amino acid substitutions designed to stabilize or destabilize
      the hairpin. The triple substitution Gly33Val-Val36Pro-Gly38Val ("VPV")
      facilitated Abeta42 hexamer and nonamer formation, while inhibiting formation of
      classical amyloid-type fibrils. These assemblies were as toxic as were assemblies
      from wild-type Abeta42. When substituted into Abeta40, the VPV substitution
      caused the peptide to oligomerize similarly to Abeta42. The modified Abeta40 was
      significantly more toxic than Abeta40. The double substitution d-Pro36-l-Pro37
      abolished hexamer and dodecamer formation by Abeta42 and produced an oligomer
      size distribution similar to that of Abeta40. Our data suggest that the Val36
      Gly37 turn could be the sine qua non of Abeta42. If true, this structure would be
      an exceptionally important therapeutic target.

PMID- 23154166
TI  - Amyloid formation in heterogeneous environments: islet amyloid polypeptide
      glycosaminoglycan interactions.
AB  - Amyloid formation plays an important role in a broad range of diseases, and the
      search for amyloid inhibitors is an active area of research. Amyloid formation
      takes places in a heterogeneous environment in vivo with the potential for
      interactions with membranes and with components of the extracellular matrix.
      Naturally occurring amyloid deposits are associated with sulfated proteoglycans
      and other factors. However, the vast majority of in vitro assays of amyloid
      formation and amyloid inhibition are conducted in homogeneous solution where the
      potential for interactions with membranes or sulfated proteoglycans is lacking
      and it is possible that different results may be obtained in heterogeneous
      environments. We show that variants of islet amyloid polypeptide (IAPP), which
      are non-amyloidogenic in homogeneous solution, can be readily induced to form
      amyloid in the presence of glycosaminoglycans (GAGs). GAGs are found to be more
      effective than anionic lipid vesicles at inducing amyloid formation on a per
      charge basis. Several known inhibitors of IAPP amyloid formation are shown to be
      less effective in the presence of GAGs.

PMID- 23154167
TI  - Native-state heterogeneity of beta(2)-microglobulin as revealed by kinetic
      folding and real-time NMR experiments.
AB  - The kinetic folding of beta(2)-microglobulin from the acid-denatured state was
      investigated by interrupted-unfolding and interrupted-refolding experiments using
      stopped-flow double-jump techniques. In the interrupted unfolding, we first
      unfolded the protein by a pH jump from pH7.5 to pH2.0, and the kinetic refolding
      assay was carried out by the reverse pH jump by monitoring tryptophan
      fluorescence. Similarly, in the interrupted refolding, we first refolded the
      protein by a pH jump from pH2.0 to pH7.5 and used a guanidine hydrochloride
      (GdnHCl) concentration jump as well as the reverse pH jump as unfolding assays.
      Based on these experiments, the folding is represented by a parallel-pathway
      model, in which the molecule with the correct Pro32 cis isomer refolds rapidly
      with a rate constant of 5-6 s(-1), while the molecule with the Pro32 trans isomer
      refolds more slowly (pH7.5 and 25 degrees C). At the last step of folding, the
      native-like trans conformer produced on the latter pathway isomerizes very slowly
      (0.001-0.002 s(-1)) into the native cis conformer. In the GdnHCl-induced
      unfolding assays in the interrupted refolding, the native-like trans conformer
      unfolded remarkably faster than the native cis conformer, and the direct GdnHCl
      induced unfolding was also biphasic, indicating that the native-like trans
      conformer is populated at a significant level under the native condition. The one
      dimensional NMR and the real-time NMR experiments of refolding further indicated
      that the population of the trans conformer increases up to 7-9% under a more
      physiological condition (pH7.5 and 37 degrees C).

PMID- 23154168
TI  - Conformational analysis of StrH, the surface-attached exo-beta-D-N
      acetylglucosaminidase from Streptococcus pneumoniae.
AB  - Streptococcus pneumoniae is a serious human pathogen that presents on its surface
      numerous proteins involved in the host-bacterium interaction. The carbohydrate
      active enzymes are particularly well represented among these surface proteins,
      and many of these are known virulence factors, highlighting the importance of
      carbohydrate processing by this pathogen. StrH is a surface-attached exo-beta-D-N
      acetylglucosaminidase that cooperates with the sialidase NanA and the beta
      galactosidase BgaA to sequentially degrade the nonreducing terminal arms of
      complex N-linked glycans. This enzyme is a large multi-modular protein that is
      notable for its tandem N-terminal family GH20 catalytic modules, whose individual
      X-ray crystal structures were recently reported. StrH also contains C-terminal
      tandem G5 modules, which are uncharacterized. Here, we report the NMR-determined
      solution structure of the first G5 module in the tandem, G5-1, which along with
      the X-ray crystal structures of the GH20 modules was used in conjunction with
      small-angle X-ray scattering to construct a pseudo-atomic model of full-length
      StrH. The results reveal a model in which StrH adopts an elongated conformation
      that may project the catalytic modules away from the surface of the bacterium to
      a distance of up to ~250 A.

PMID- 23154169
TI  - Structure-based redesign of the binding specificity of anti-apoptotic Bcl-x(L).
AB  - Many native proteins are multi-specific and interact with numerous partners,
      which can confound analysis of their functions. Protein design provides a
      potential route to generating synthetic variants of native proteins with more
      selective binding profiles. Redesigned proteins could be used as research tools,
      diagnostics or therapeutics. In this work, we used a library screening approach
      to reengineer the multi-specific anti-apoptotic protein Bcl-x(L) to remove its
      interactions with many of its binding partners, making it a high-affinity and
      selective binder of the BH3 region of pro-apoptotic protein Bad. To overcome the
      enormity of the potential Bcl-x(L) sequence space, we developed and applied a
      computational/experimental framework that used protein structure information to
      generate focused combinatorial libraries. Sequence features were identified using
      structure-based modeling, and an optimization algorithm based on integer
      programming was used to select degenerate codons that maximally covered these
      features. A constraint on library size was used to ensure thorough sampling.
      Using yeast surface display to screen a designed library of Bcl-x(L) variants, we
      successfully identified a protein with ~1000-fold improvement in binding
      specificity for the BH3 region of Bad over the BH3 region of Bim. Although
      negative design was targeted only against the BH3 region of Bim, the best
      redesigned protein was globally specific against binding to 10 other peptides
      corresponding to native BH3 motifs. Our design framework demonstrates an
      efficient route to highly specific protein binders and may readily be adapted for
      application to other design problems.

PMID- 23154170
TI  - Structural and biophysical characterization of the Syk activation switch.
AB  - Syk is an essential non-receptor tyrosine kinase in intracellular immunological
      signaling, and the control of Syk kinase function is considered as a valuable
      target for pharmacological intervention in autoimmune or inflammation diseases.
      Upon immune receptor stimulation, the kinase activity of Syk is regulated by
      binding of phosphorylated immune receptor tyrosine-based activating motifs
      (pITAMs) to the N-terminal tandem Src homology 2 (tSH2) domain and by
      autophosphorylation with consequences for the molecular structure of the Syk
      protein. Here, we present the first crystal structures of full-length Syk (fl
      Syk) as wild type and as Y348F,Y352F mutant forms in complex with AMP-PNP
      revealing an autoinhibited conformation. The comparison with the crystal
      structure of the truncated Syk kinase domain in complex with AMP-PNP taken
      together with ligand binding studies by surface plasmon resonance (SPR) suggests
      conformational differences in the ATP sites of autoinhibited and activated Syk
      forms. This hypothesis was corroborated by studying the thermodynamic and kinetic
      interaction of three published Syk inhibitors with isothermal titration
      calorimetry and SPR, respectively. We further demonstrate the modulation of
      inhibitor binding affinities in the presence of pITAM and discuss the observed
      differences of thermodynamic and kinetic signatures. The functional relevance of
      pITAM binding to fl-Syk was confirmed by a strong stimulation of in vitro
      autophosphorylation. A structural feedback mechanism on the kinase domain upon
      pITAM binding to the tSH2 domain is discussed in analogy of the related family
      kinase ZAP-70 (Zeta-chain-associated protein kinase 70). Surprisingly, we
      observed distinct conformations of the tSH2 domain and the activation switch
      including Tyr348 and Tyr352 in the interdomain linker of Syk in comparison to ZAP
      70.

PMID- 23154171
TI  - The molten globule of beta(2)-microglobulin accumulated at pH 4 and its role in
      protein folding.
AB  - The acid transition of beta(2)-microglobulin (beta2m) was studied by tryptophan
      fluorescence, peptide circular dichroism, and NMR spectroscopy. The protein
      exhibits a three-state transition with an equilibrium intermediate accumulated at
      pH4 (25 degrees C). The pH4 intermediate has typical characteristics of the
      molten globule (MG) state; it showed a native-like secondary structure without
      specific side-chain tertiary structure, and the hydrodynamic radius determined by
      pulse field gradient NMR was only 20% larger than that of the native state. The
      accumulation of the pH4 intermediate is very analogous to the behavior of
      apomyoglobin, for which the pH4 MG has been well characterized, although beta2m,
      a beta-protein, is structurally very different from alpha-helical apomyoglobin.
      NMR pH titration of histidine residues of beta2m has also indicated that His84
      has an abnormally low pK(a) value in the native state. From the pH dependence of
      the unfolding transition, the protonations of this histidine and 10 weakly
      abnormal carboxylates triggered the transition from the native to the MG state.
      This behavior is again analogous to that of apomyoglobin, suggesting a common
      mechanism of production of the pH4 MG. In contrast to the folding of
      apomyoglobin, in which the MG was equivalent to the burst-phase kinetic folding
      intermediate, the burst-phase refolding intermediate of beta2m, detected by
      stopped-flow circular dichroism, was significantly more structured than the pH4
      intermediate. It is proposed that the folding of beta2m from its acid-denatured
      state takes place in the following order: denatured state->MG->burst-phase
      intermediate->native state.

PMID- 23154173
TI  - [New in the medical press?].

PMID- 23154174
TI  - Quantitative bone ultrasound in pediatric patients with cystic fibrosis.

PMID- 23154175
TI  - Standardized outpatient management of Klebsiella pneumoniae liver abscesses.
AB  - OBJECTIVES: Community-acquired Klebsiella pneumoniae has emerged as a major cause
      of liver abscess in Asia. Using a standardized protocol, we conducted a
      prospective cohort study of all cases of K. pneumoniae liver abscess treated from
      2005 to 2011 at two outpatient parenteral antimicrobial therapy (OPAT) centers in
      Singapore, to assess the safety and efficacy of treatment. METHODS: We included
      all OPAT eligible patients with radiologically confirmed (computed tomography or
      ultrasound) liver abscesses and K. pneumoniae-positive microbiological cultures
      obtained from abscess fluid and/or blood at two university teaching hospitals.
      The endpoints investigated were cure, clinical response, readmission, and
      mortality. RESULTS: All 109 patients enrolled in the study successfully completed
      treatment in OPAT. Nine patients required a short-term readmission due to
      clinical deterioration. There were no deaths or relapses at 30 days post
      cessation of antibiotics. Abscess size greater than 5 cm was associated with a
      delayed clinical response (odds ratio 5.34, 95% confidence interval 1.25-22.91, p
      = 0.02). CONCLUSION: The management of K. pneumoniae liver abscesses via OPAT
      using a standardized protocol is a safe and effective alternative to inpatient
      intravenous antibiotics.

PMID- 23154176
TI  - Is hepatitis B virus transmitted via the male germ line? A seroepidemiological
      study in fetuses.
AB  - OBJECTIVES: To detect father-to-fetus transmission of hepatitis B virus (HBV) in
      utero. METHODS: We conducted a study at the prenatal diagnosis center of Taizhou
      City. Fetuses with one or both parents carrying the hepatitis B surface antigen
      (HBsAg) were identified before genetic testing during the period 2008-2010.
      Intrauterine samples were obtained by amniocentesis or cordocentesis and tested
      for serological markers and by quantitative DNA assays. All neonates received
      combined hepatitis B immunoprophylaxis after delivery, and serological follow-up
      tests were performed at 1 year of age. RESULTS: Of the 407 couples enrolled in
      the study, HBV was carried by fathers only in 164, and none of their fetuses were
      found to be HBV DNA-positive in utero. All fetal serological markers were found
      to be of maternal but not paternal origin. The response rate to postnatal
      vaccination was 98.6%, and none of the children who failed immunoprophylaxis were
      the offspring of the HBV carrier fathers. CONCLUSIONS: The infection of fetuses
      with HBV from the spermatozoa of carrier fathers seems unlikely, especially in an
      area where pre-conception hepatitis B vaccination is routinely provided.

PMID- 23154177
TI  - Impact evaluation of a sexually transmitted disease preventive intervention among
      female sex workers in Hohhot, China.
AB  - OBJECTIVES: The aim of this study was to evaluate the impact of HIV and sexually
      transmitted disease (STD) prevention interventions among female sex workers
      (FSWs) in the city of Hohhot in northern China. METHODS: Three serial cross
      sectional surveys were conducted in 2006, 2007, and 2008 among FSWs. A
      questionnaire was administered to the FSWs, and HIV and syphilis tests were
      performed for all participants. Intervention activities including condom
      promotion and provision, increased condom availability and accessibility, and
      voluntary HIV counseling and testing (VCT) were carried out among FSWs. RESULTS:
      There were 624 participants in the 2006 survey, 444 in the 2007 survey, and 451
      in the 2008 survey. The United Nations General Assembly Special Session (UNGASS)
      indicators for FSWs increased from 13.9% in 2006 to 37.7% in 2008 (p<0.001). The
      average rate of consistent condom use with commercial clients in the month
      preceding the interview increased significantly from 39.8% in 2006 to 59.6% in
      2008 (p<0.001). Not a single HIV-positive case was found among the FSWs over
      these 3 years, and the prevalence of syphilis decreased remarkably from 9.5% in
      2006 to 1.3% in 2008. Logistic regression analysis showed that sauna or hair
      salon work venues, receiving services from intervention programs, and accepting
      HIV tests were factors associated with consistent condom use. CONCLUSIONS: The
      findings suggest that consistent condom use and awareness of HIV/AIDS prevention
      related knowledge among FSWs have been improved by the intervention. Further
      prioritized and combined prevention programs aimed at FSWs are needed in order to
      prevent the HIV/AIDS epidemic spreading in the general population in China.

PMID- 23154178
TI  - Initial characterization of a dually radiolabeled peptide for simultaneous
      monitoring of protein targets and enzymatic activity.
AB  - OBJECTIVE: The goal of this study was to develop dually radiolabeled peptides for
      simultaneous imaging of cancer cell localization by targeting the alpha(v)beta(3)
      integrin and their pathophysiology by targeting the activity of the proteolytic
      enzyme MMP2, involved in the metastatic process. METHODS: A hybrid peptide
      c(RGDfE)K(DOTA)PLGVRY containing an RGD motif for binding to the
      alpha(v)beta(3)integrin, a metal chelator (DOTA) for radiolabeling with [(64)Cu],
      and the MMP2 substrate cleavage sequence PLGVRY with terminal tyrosine for
      labeling with [(123)I] was synthesized, labeled with [(64)Cu] and [(123)I], and
      evaluated in vitro as a potential imaging agent. RESULTS: The peptide was
      synthesized and labeled with [(64)Cu] and [(123)I] with 300 and 40 MUCi/MUg (542
      and 72.2 mCi/MUmol) specific activities, respectively, and radiochemical purity
      of >98%. c(RGDfE)K(DOTA)PLGVRY demonstrated high affinity for alpha(v)beta(3)
      integrins (Kd=83.4+13.2 nM) in both substrate competition and cell binding
      assays. c(RGDfE)K(DOTA)PLGVRY peptide, but not the scrambled version,
      c(RGDfE)K(DOTA)GRPLVY was specifically cleaved by MMP2. CONCLUSIONS: These
      results demonstrate the feasibility of developing dually radiolabeled peptides
      for the simultaneous imaging of cancer cells and their pathophysiologic activity.

PMID- 23154180
TI  - Simvastatin inhibits the core promoter of the TXNRD1 gene and lowers cellular
      TrxR activity in HepG2 cells.
AB  - Thioredoxin reductase 1 (TrxR1) is a selenocysteine-containing redox-active
      enzyme that is thought to be important during carcinogenesis. We have recently
      shown that treatment with statins, HMGCoA reductase inhibitors, reduces the
      levels of TrxR1 in liver of both rat and human. The reduced TrxR1 levels were
      correlated with inhibited hepatocarcinogenesis in a rat model. The aim of the
      present study was to investigate if statins affect the activity of the human
      TXNRD1 core promoter, which guides expression of TrxR1, and if the effects by
      statins on TrxR1 expression in liver could be reproduced in a cellular model
      system. We found that simvastatin and fluvastatin decreased cellular TrxR
      activity in cultured human liver-derived HepG2 cells with approximately 40%
      (p<0.05). Simvastatin, but not fluvastatin or atorvastatin, also reduced the
      TXNRD1 promoter activity in HepG2 cells by 20% (p<0.01). In line with this
      result, TrxR1 mRNA levels decreased with about 25% in non-transfected HepG2 cells
      upon treatment with simvastatin (p<0.01). Concomitant treatment with mevalonate
      could not reverse these effects of simvastatin, indicating that other mechanisms
      than HMGCoA reductase inhibition was involved. Also, simvastatin did not inhibit
      sulforaphane-derived stimulation of the TXNRD1 core promoter activity, suggesting
      that the inhibition by simvastatin was specific for basal and not Nrf2-activated
      TrxR1 expression. In contrast to simvastatin, the two other statins tested,
      atorvastatin or fluvastatin, did not influence the TrxR1 mRNA levels. Thus, our
      results reveal a simvastatin-specific reduction of cellular TrxR1 levels that at
      least in part involves direct inhibitory effects on the basal activity of the
      core promoter guiding TrxR1 expression.

PMID- 23154179
TI  - In vivo evidence that Agxt2 can regulate plasma levels of dimethylarginines in
      mice.
AB  - Elevated plasma concentrations of the asymmetric (ADMA) and symmetric (SDMA)
      dimethylarginine have repeatedly been linked to adverse cardiovascular clinical
      outcomes. Both dimethylarginines can be degraded by alanine-glyoxylate
      aminotransferase 2 (Agxt2), which is also the key enzyme responsible for the
      degradation of endogenously formed beta-aminoisobutyrate (BAIB). In the present
      study we wanted to investigate the effect of BAIB on Agxt2 expression and Agxt2
      mediated metabolism of dimethylarginines. We infused BAIB or saline
      intraperitoneally for 7days in C57/BL6 mice via minipumps. Expression of Agxt2
      was determined in liver and kidney. The concentrations of BAIB, dimethylarginines
      and the Agxt2-specific ADMA metabolite alpha-keto-delta-(N(G),N(G)
      dimethylguanidino)valeric acid (DMGV) was determined by LC-MS/MS in plasma and
      urine. As compared to controls systemic administration of BAIB increased plasma
      and urine BAIB levels by a factor of 26.5 (p<0.001) and 25.8 (p<0.01),
      respectively. BAIB infusion resulted in an increase of the plasma ADMA and SDMA
      concentrations of 27% and 31%, respectively, (both p<0.05) and a 24% decrease of
      plasma DMGV levels (p<0.05), while expression of Agxt2 was not different. Our
      data demonstrate that BAIB can inhibit Agxt2-mediated metabolism of
      dimethylarginines and show for the first time that endogenous Agxt2 is involved
      in the regulation of systemic ADMA, SDMA and DMGV levels. The effect of BAIB
      excess on endogenous dimethylarginine levels may have direct clinical
      implications for humans with the relatively common genetic trait of hyper-beta
      aminoisobutyric aciduria.

PMID- 23154181
TI  - SnoN/SKIL modulates proliferation through control of hsa-miR-720 transcription in
      esophageal cancer cells.
AB  - It is now evident that changes in microRNA are involved in cancer progression,
      but the mechanisms of transcriptional regulation of miRNAs remain unknown. Ski
      related novel gene (SnoN/SKIL), a transcription co-factor, acts as a potential
      key regulator within a complex network of p53 transcriptional repressors. SnoN
      has pro- and anti-oncogenic functions in the regulation of cell proliferation,
      senescence, apoptosis, and differentiation. We characterized the roles of SnoN in
      miRNA transcriptional regulation and its effects on cell proliferation using
      esophageal squamous cell carcinoma (ESCC) cells. Silencing of SnoN altered a set
      of miRNA expression profiles in TE-1cells, and the expression levels of miR-720,
      miR-1274A, and miR-1274B were modulated by SnoN. The expression of these miRNAs
      resulted in changes to the target protein p63 and a disintegrin and
      metalloproteinase domain 9 (ADAM9). Furthermore, silencing of SnoN significantly
      upregulated cell proliferation in TE-1 cells, indicating a potential anti
      oncogenic function. These results support our observation that cancer tissues
      have lower expression levels of SnoN, miR-720, and miR-1274A compared to adjacent
      normal tissues from ESCC patients. These data demonstrate a novel mechanism of
      miRNA regulation, leading to changes in cell proliferation.

PMID- 23154182
TI  - IL-35 over-expression increases apoptosis sensitivity and suppresses cell growth
      in human cancer cells.
AB  - Interleukin (IL)-35 is a novel heterodimeric cytokine in the IL-12 family and is
      composed of two subunits: Epstein-Barr virus-induced gene 3 (EBI3) and IL-12p35.
      IL-35 is expressed in T regulatory (Treg) cells and contributes to the immune
      suppression function of these cells. In contrast, we found that both IL-35
      subunits were expressed concurrently in most human cancer cell lines compared to
      normal cell lines. In addition, we found that TNF-alpha and IFN-gamma stimulation
      led to increased IL-35 expression in human cancer cells. Furthermore, over
      expression of IL-35 in human cancer cells suppressed cell growth in vitro,
      induced cell cycle arrest at the G1 phase, and mediated robust apoptosis induced
      by serum starvation, TNF-alpha, and IFN-gamma stimulation through the up
      regulation of Fas and concurrent down-regulation of cyclinD1, survivin, and Bcl-2
      expression. In conclusion, our results reveal a novel functional role for IL-35
      in suppressing cancer activity, inhibiting cancer cell growth, and increasing the
      apoptosis sensitivity of human cancer cells through the regulation of genes
      related to the cell cycle and apoptosis. Thus, this research provides new
      insights into IL-35 function and presents a possible target for the development
      of novel cancer therapies.

PMID- 23154183
TI  - Regulation of cooperative function of the Il12b enhancer and promoter by the
      interferon regulatory factors 3 and 5.
AB  - The regulation of the Il12b gene, encoding the shared p40 subcomponent for IL-12
      and IL-23, is critical for innate immune responses and subsequent T cell
      polarization. This gene is robustly induced upon Toll-like receptor (TLR)
      stimulation, wherein an enhancer located 10kb upstream of the transcription start
      site is required for promoter activity; however, the underlying mechanisms that
      regulate this enhancer in cooperation with the promoter has remained elusive. We
      show here that the Il12b enhancer contains functional ISREs for recognition by
      interferon regulatory factors (IRFs), and provide evidence that TLR-activated
      IRF5 mediates cooperativity of the enhancer with the promoter which also contains
      ISREs. By contrast, IRF3 activated by cytosolic RIG-I-like receptor (RLR)
      signaling binds to these ISREs and causes gene suppression. Consistently, IRF5
      binding is accompanied with chromatin remodeling of both regulatory regions and
      the formation of a productive transcriptional complex containing other
      transcription factors, whereas these events are inhibited by IRF3 binding. We
      show that the ISREs embedded in the enhancer are indeed critical for its
      activation by IRF5. We also adduce evidence that the 5' sequences of the enhancer
      and promoter ISREs, all of which deviate from consensus ISREs, critically affect
      the function of IRF3. The dual commitment of these IRFs in the regulation of the
      Il12b enhancer and promoter is unique and may have implications for understanding
      the evolution of this gene.

PMID- 23154184
TI  - Effect of taurine and N-acetylcysteine on methionine restriction-mediated
      adiposity resistance.
AB  - OBJECTIVES: Methionine-restricted (MR) rats, which are lean and insulin
      sensitive, have low serum total cysteine (tCys) and taurine and decreased hepatic
      expression and activity indices of stearoyl-coenzyme A desaturase-1 (SCD1). These
      effects are partly or completely reversed by cysteine supplementation. We
      investigated whether reversal of MR phenotypes can be achieved by other sulfur
      compounds, namely taurine or N-acetylcysteine (NAC). METHODS: MR and control-fed
      (CF) rats were supplemented with taurine (0.5%) or NAC (0.5%) for 12weeks.
      Adiposity, serum sulfur amino acids (SAA), Scd1 gene expression in liver and
      white adipose tissue, and SCD1 activity indices (calculated from serum fatty acid
      profile) were monitored. RESULTS: Taurine supplementation of MR rats did not
      restore weight gain or hepatic Scd1 expression or indices to CF levels, but
      further decreased adiposity. Taurine supplementation of CF rats did not affect
      adiposity, but lowered triglyceridemia. NAC supplementation in MR rats raised
      tCys and partly or completely reversed MR effects on weight, fat %, Scd1
      expression in liver and white adipose tissue, and estimated SCD1 activity. In CF
      rats, NAC decreased body fat % and lowered SCD1-18 activity index (P<0.001).
      Serum triglycerides and leptin were over 40% lower in CF+NAC relative to CF rats
      (P<=0.003 for both). In all groups, change in tCys correlated with change in SCD1
      16 index (partial r=0.60, P<0.001) independent of other SAA. CONCLUSION: The
      results rule out taurine as a mediator of increased adiposity produced by
      cysteine in MR, and show that NAC, similar to L-cysteine, blocks anti-obesity
      effects of MR. Our data show that dietary SAA can influence adiposity in part
      through mechanisms that converge on SCD1 function. This may have implications for
      understanding and preventing human obesity.

PMID- 23154185
TI  - Zinc and pregnancy: Marked changes on the immune response following zinc therapy
      for pregnant females challenged with Trypanosoma cruzi.
AB  - BACKGROUND & AIMS: The occurrence of infectious disease processes during
      pregnancy has significant effects on maternal health and can lead to adverse
      pregnancy outcomes. The aim of the present study was to examine the potential
      role of zinc treatment during Trypanosoma cruzi infection in pregnant animals.
      METHODS: Female Wistar rats weighing 180-200 g were used in all experiments.
      Production of nitric oxide, peritoneal macrophages counts, and concentrations of
      IFN-gamma and TNF-alpha were measured, and the potential protective effects of
      zinc on fetal development were assessed at 14-day post-infection. RESULTS: Nitric
      oxide concentrations were higher in pregnant zinc-treated animals than in their
      untreated counterparts, despite similar levels of the macrophages, IFN-gamma and
      TNF-alpha. Zinc therapy was associated with a significant reduction in
      parasitemia and cardiac parasite burden. Higher placental and birth weights were
      observed in animals given prenatal zinc supplementation compared to untreated
      animals. CONCLUSIONS: These data confirm the critical importance of adequate zinc
      intake during the peri-conceptional period and indicate that zinc has an
      effective role in preventing adverse outcomes of pregnancy and reducing the risk
      of common infections such as Chagas' disease.

PMID- 23154186
TI  - Subthreshold vestibular reflex effects in seated humans can contribute to soleus
      activation when combined with cutaneous inputs.
AB  - The integration of vestibular and somatosensory information for the control of
      lower limb musculature remains elusive. To determine whether a subthreshold
      vestibular input influences the cutaneous evoked response, the isometric EMG
      activity in the posturally inactive soleus muscles of 13 healthy, seated subjects
      was collected. Vestibular afferents were activated using galvanic vestibular
      stimulation (GVS; 1.8-2.5mA, 500ms), while percutaneous electrical stimulation
      was delivered to the distal tibial nerve (11ms train of 3 * 1.0 ms pulses, 200Hz)
      to activate foot sole skin afferents. GVS elicited responses in soleus both
      independently and when combined with cutaneous stimulation. The responses to the
      combined sensory input showed an interaction between the two sensory modalities
      to influence muscle activation. Of note is the presence of significant muscle
      modulation in the combined condition, where subthreshold vestibular inputs
      altered the outcome of the cutaneous reflex response. This finding has
      implications for individuals with sensory deficiency. In the case of an absent or
      deficient sensory modality, balance protective reflexes to maintain postural
      equilibrium may be enhanced with targeted sensory augmentation.

PMID- 23154187
TI  - Behavior of the magnetization in spin-locking magnetic resonance imaging using
      numerical solutions to the time-dependent Bloch equations.
AB  - We present a simple method for calculating the magnetization in spin-locking (SL)
      magnetic resonance imaging (MRI), in which a simple matrix equation was derived
      for solving the time-dependent Bloch equations in the 2-pool chemical exchange
      model. We also present a method for visualizing the trajectory of a magnetization
      vector in a three-dimensional (3D) space. The longitudinal relaxation time in the
      rotating frame (T(1rho)) was calculated by fitting the z component of
      magnetization for a duration of SL (t(SL)) (M(z)(t(SL))) to M(z)(t(SL)) = (M(0) -
      M(zss))exp ( - t(SL)/T(1rho)) + M(zss), where M(0) and M(z)(ss) denote the
      thermal equilibrium and steady-state z component of magnetization, respectively,
      and was compared with that calculated from the solution given by Trott and
      Palmer. Our 3D plots clearly visualized the effect of SL. When the population of
      the two pools was highly asymmetric, there was good agreement between the T(1rho)
      values obtained by our method and Trott and Palmer's solutions. The difference
      between them increased with decreasing asymmetry in the population of the two
      pools. Our method will be useful for better understanding and optimization of SL
      MRI, because it allows us to calculate the magnetization vector and to visualize
      its trajectory simply and quickly.

PMID- 23154188
TI  - Protein space: a natural method for realizing the nature of protein universe.
AB  - Current methods cannot tell us what the nature of the protein universe is
      concretely. They are based on different models of amino acid substitution and
      multiple sequence alignment which is an NP-hard problem and requires manual
      intervention. Protein structural analysis also gives a direction for mapping the
      protein universe. Unfortunately, now only a minuscule fraction of proteins' 3
      dimensional structures are known. Furthermore, the phylogenetic tree
      representations are not unique for any existing tree construction methods. Here
      we develop a novel method to realize the nature of protein universe. We show the
      protein universe can be realized as a protein space in 60-dimensional Euclidean
      space using a distance based on a normalized distribution of amino acids. Every
      protein is in one-to-one correspondence with a point in protein space, where
      proteins with similar properties stay close together. Thus the distance between
      two points in protein space represents the biological distance of the
      corresponding two proteins. We also propose a natural graphical representation
      for inferring phylogenies. The representation is natural and unique based on the
      biological distances of proteins in protein space. This will solve the
      fundamental question of how proteins are distributed in the protein universe.

PMID- 23154189
TI  - A metapopulation model for chikungunya including populations mobility on a large
      scale network.
AB  - In this paper we study the influence of populations mobility on the spread of a
      vector-borne disease. We focus on the chikungunya epidemic event that occurred in
      2005-2006 on the Reunion Island, Indian Ocean, France, and validate our models
      with real epidemic data from the event. We propose a metapopulation model to
      represent both a high-resolution patch model of the island with realistic
      population densities and also mobility models for humans (based on real-motion
      data) and mosquitoes. In this metapopulation network, two models are coupled: one
      for the dynamics of the mosquito population and one for the transmission of the
      disease. A high-resolution numerical model is created from real geographical,
      demographical and mobility data. The Island is modeled with an 18,000-nodes
      metapopulation network. Numerical results show the impact of the geographical
      environment and populations' mobility on the spread of the disease. The model is
      finally validated against real epidemic data from the Reunion event.

PMID- 23154190
TI  - Mathematical modeling of insulin secretion and the role of glucose-dependent
      mobilization, docking, priming and fusion of insulin granules.
AB  - In this paper we develop a new mathematical model of glucose-induced insulin
      secretion from pancreatic islet beta-cells, and we use this model to investigate
      the rate limiting factors. We assume that insulin granules reside in different
      pools inside each beta-cell, and that all beta-cells respond homogeneously to
      glucose with the same recruitment thresholds. Consistent with recent experimental
      observations, our model also accounts for the fusion of newcomer granules that
      are not pre-docked at the plasma membrane. In response to a single step increase
      in glucose concentration, our model reproduces the characteristic biphasic
      insulin release observed in multiple experimental systems, including perfused
      pancreata and isolated islets of rodent or human origin. From our model analysis
      we note that first-phase insulin secretion depends on rapid depletion of the
      primed, release-ready granule pools, while the second phase relies on granule
      mobilization from the reserve. Moreover, newcomers have the potential to
      contribute significantly to the second phase. When the glucose protocol consists
      of multiple changes in sequence (a so-called glucose staircase), our model
      predicts insulin spikes of increasing height, as has been seen experimentally.
      This increase stems from the glucose-dependent increase in the fusion rate of
      insulin granules at the plasma membrane of single beta-cells. In contrast,
      previous mathematical models reproduced the staircase experiment by assuming
      heterogeneous beta-cell activation. In light of experimental data indicating
      limited heterogeneous activation for beta-cells within intact islets, our
      findings suggest that a graded, dose-dependent cell response to glucose may
      contribute to insulin secretion patterns observed in multiple experiments, and
      thus regulate in vivo insulin release. In addition, the strength of insulin
      granule mobilization, priming and fusion are critical limiting factors in
      determining the total amount of insulin release.

PMID- 23154191
TI  - The effect of Fe-coverage on the structure, morphology and magnetic properties of
      alpha-FeSi2 nanoislands.
AB  - Self-assembled alpha-FeSi(2) nanoislands were formed using solid-phase epitaxy of
      low (~1.2 ML) and high (~21 ML) Fe coverages onto vicinal Si(111) surfaces
      followed by thermal annealing. At a resulting low Fe-covered Si(111) surface, we
      observed in situ, by real-time scanning tunneling microscopy and surface electron
      diffraction, the entire sequence of Fe-silicide formation and transformation from
      the initially two-dimensional (2 * 2)-reconstructed layer at 300  degrees C into
      (2 * 2)-reconstructed nanoislands decorating the vicinal step-bunch edges in a
      self-ordered fashion at higher temperatures. In contrast, the silicide
      nanoislands at a high Fe-covered surface were noticeably larger, more three
      dimensional, and randomly distributed all over the surface. Ex situ x-ray
      photoelectron spectroscopy and high-resolution transmission electron microscopy
      indicated the formation of an alpha-FeSi(2) island phase, in an alpha
      FeSi(2){112} // Si{111} orientation. Superconducting quantum interference device
      magnetometry showed considerable superparamagnetism, with ~1.9 MU(B)/Fe atom at 4
      K for the low Fe-coverage, indicating stronger ferromagnetic coupling of
      individual magnetic moments, as compared to high Fe-coverage, where the
      calculated moments were only ~0.8 MU(B)/Fe atom. Such anomalous magnetic
      behavior, particularly for the low Fe-coverage case, is radically different from
      the non-magnetic bulk alpha-FeSi(2) phase, and may open new pathways to high
      density magnetic memory storage devices.

PMID- 23154192
TI  - The impact of breastfeeding on FTO-related BMI growth trajectories: an
      application to the Raine pregnancy cohort study.
AB  - INTRODUCTION: For years, body mass index (BMI) has been used by scientists to
      track weight problems and obesity in children and adults. Recent studies have
      implicated the fat mass and obesity gene (FTO) in the increase of BMI in young
      adults. A longer duration of breastfeeding is known to reduce the risk of being
      overweight later in life, but its ability to modify the effect because of FTO is
      not known. METHODS: We studied 1096 children from the Western Australian
      Pregnancy (Raine) cohort who were followed up from birth to 14 years of age.
      Linear mixed-effects models were used to investigate BMI growth trajectories in
      boys and girls separately. RESULTS: An association was found between BMI growth
      and the duration of exclusive breastfeeding (EXBF) among carriers of the risk
      allele of the FTO SNP rs9939609. In girls, EXBF interacts with the SNP at
      baseline and can reverse the increase in BMI because of SNP risk allele by age 14
      years after 3 months of EXBF. In boys, EXBF reduces BMI both in carriers and non
      carriers of the risk allele with an association found after 10 years of age. Six
      months of EXBF will put the boys' BMI growth curves back to the normal range.
      CONCLUSIONS: Our study could have major health implications by providing new
      perspectives for the prevention of growth problems in children carrying risk
      alleles in the FTO gene.

PMID- 23154194
TI  - Amino acid derivatives as transdermal permeation enhancers.
AB  - Transdermal permeation enhancers are compounds that temporarily decrease skin
      barrier properties to promote drug flux. In this study, we investigated enhancers
      with amino acids (proline, sarcosine, alanine, beta-alanine, and glycine)
      attached to hydrophobic chain(s) via a biodegradable ester link. The double-chain
      lipid-like substances displayed no enhancing effect, whereas single-chain
      substances significantly increased skin permeability. The proline derivative l
      Pro2 reached enhancement ratios of up to 40 at 1% concentration, which is higher
      than that of the well-established and standard enhancers Azone, DDAIP, DDAK, and
      Transkarbam 12. No stereoselectivity was observed. l-Pro2 acted synergistically
      with propylene glycol. Infrared studies revealed that l-Pro2 forms a separate
      liquid ordered phase in the stratum corneum lipids and has no significant effect
      on proteins. l-Pro2 action was at least partially reversible as measured by skin
      electrical impedance. Toxicity in keratinocyte (HaCaT) and fibroblast (3T3) cell
      lines showed IC(50) values ranging from tens to hundreds of MUM, which is
      comparable with standard enhancers. Furthermore, l-Pro2 was rapidly decomposed in
      plasma. In vivo transdermal absorption studies in rats confirmed the enhancing
      activity of l-Pro2 and suggested its negligible skin toxicity and minimal effect
      on transepidermal water loss. These properties make l-Pro2 a promising candidate
      for potential clinical use.

PMID- 23154193
TI  - Controlled delivery of heparin-binding EGF-like growth factor yields fast and
      comprehensive wound healing.
AB  - Wound healing is a dynamic process that relies on coordinated signaling molecules
      to succeed. Heparin-binding epidermal growth factor (EGF)-like growth factor (HB
      EGF) is proven to accelerate healing, however precise control over its
      application is necessary to reduce side effects and achieve desired therapeutic
      benefit. To achieve effective growth factor delivery we designed a bioactive
      heparin-based coacervate. In vitro, HB-EGF released from the coacervate delivery
      system displayed enhanced bioactivity and promoted human keratinocyte migration
      while preserving cell proliferative capability. In a mouse excisional full
      thickness wound model, controlled release of HB-EGF within the wound
      significantly accelerated wound closure more effectively than an equal dosage of
      free HB-EGF. Healing was induced by rapid re-epithelialization, granulation
      tissue formation, and accompanied by angiogenesis. Consistent with in vitro
      results, wounds treated with HB-EGF coacervate exhibited enhanced migration of
      keratinocytes with retained proliferative potential, forming a confluent layer
      for regained barrier function within 7 days. Collectively, these results suggest
      that coacervate-based controlled release of HB-EGF may serve as a new therapy to
      accelerate healing of cutaneous wounds.

PMID- 23154195
TI  - Sox2 regulation of hair cell development: incoherence makes sense.
AB  - The function of the inner ear relies on different specialized cell types: hair
      cells, supporting cells and otic neurons. During development, these cell types
      are generated from the neurosensory domain of the otic placode with a stereotyped
      spatial and temporal pattern. We discuss here the role played by Sox2 in the
      establishment of the neurosensory competence at early stages of inner ear
      development, and how this resolves in the sequential generation of neurons and
      hair cells. Sox2 is expressed in the neurosensory domain of the otic placode and
      it is necessary and sufficient for hair cell development. The prosensory function
      of Sox2 relies on its ability to directly bind Atoh1 regulatory regions and
      activate its expression. This function is likely mediated through the interaction
      with partner factors, some of which are just starting to be disclosed. However,
      the regulation of proneural genes by Sox2 is seemingly contradictory, because it
      also inhibits the function of Atoh1 and hence the differentiation of hair cells.
      This is because Sox2 triggers an incoherent feed forward loop by which in
      parallel to the activation of Atoh1, Sox2 also induces inhibitory factors that
      counteract its function. As a result, neurosensory competence is established in
      the early otic placode but hair cell differentiation procrastinated. More
      generally, this suggests that cell diversification may arise from the selective
      de-repression of an initial multicompetent state.

PMID- 23154196
TI  - Effects of passive, moderate-level sound exposure on the mature auditory cortex:
      spectral edges, spectrotemporal density, and real-world noise.
AB  - Persistent, passive exposure of adult cats to bandlimited tone pip ensembles or
      sharply-filtered white noise at moderate levels (~70 dB SPL) leads to a long-term
      suppression of spontaneous and sound-evoked activity in the region(s) of primary
      auditory cortex (AI) normally tuned to the exposure spectrum, and to an
      enhancement of activity in one or more neighboring regions of AI, all in the
      apparent absence of hearing loss. Here, we first examined the effects of passive
      exposure to a more structured, real-world noise, consisting of a mix of power
      tool and construction sounds. This "factory noise" had less pronounced effects on
      adult cat AI than our previous random tone pip ensembles and white noise, and
      these effects appeared limited to the region of AI tuned to frequencies near the
      sharp factory noise cutoff at 16 kHz. To further investigate the role of sharp
      spectral edges in passive exposure-induced cortical plasticity, a second group of
      adult cats was exposed to a tone pip ensemble with a flat spectrum between 2 and
      4 kHz and shallow cutoff slopes (12 dB/oct) on either side. Compared to our
      previous ensemble with the same power in the 2-4 kHz band but very steep slopes,
      exposure to the overall more intense, sloped stimulus had much weaker effects on
      AI. Finally, we explored the issue of exposure stimulus spectrotemporal density
      and found that low aggregate tone pip presentation rates of about one per second
      sufficed to induce changes in the adult AI similar to those characteristic of our
      previous, much denser exposures. These results are discussed in light of the
      putative mechanisms underlying exposure-induced auditory cortical plasticity, and
      the potential adverse consequences of working or living in moderately noisy
      environments.

PMID- 23154197
TI  - Risk modelling in quality clinical registries: monitoring lesion treatment
      failure rate in percutaneous coronary interventions.
AB  - AIMS: This paper describes the development of a risk adjustment (RA) model
      predictive of individual lesion treatment failure in percutaneous coronary
      interventions (PCI) for use in a quality monitoring and improvement program.
      METHODS AND RESULTS: Prospectively collected data for 3972 consecutive
      revascularisation procedures (5601 lesions) performed between January 2003 and
      September 2011 were studied. Data on procedures to September 2009 (n=3100) were
      used to identify factors predictive of lesion treatment failure. Factors
      identified included lesion risk class (p<0.001), occlusion type (p<0.001),
      patient age (p=0.001), vessel system (p<0.04), vessel diameter (p<0.001),
      unstable angina (p=0.003) and presence of major cardiac risk factors (p=0.01). A
      Bayesian RA model was built using these factors with predictive performance of
      the model tested on the remaining procedures (area under the receiver operating
      curve: 0.765, Hosmer-Lemeshow p value: 0.11). Cumulative sum, exponentially
      weighted moving average and funnel plots were constructed using the RA model and
      subjectively evaluated. CONCLUSION: A RA model was developed and applied to SPC
      monitoring for lesion failure in a PCI database. If linked to appropriate quality
      improvement governance response protocols, SPC using this RA tool might improve
      quality control and risk management by identifying variation in performance based
      on a comparison of observed and expected outcomes.

PMID- 23154198
TI  - Early identification of asymptomatic subjects at increased risk of heart failure
      and cardiovascular events: progress and future directions.
AB  - Increasing evidence for a latent, preclinical phase of cardiac pathology prior to
      the development of symptomatic heart failure has fuelled interest in the
      potential of developing a screening program for early disease detection and
      intervention. Cardiac biomarkers have shown promise in identifying subjects with
      significant left ventricular dysfunction and more recently to assist in
      cardiovascular risk stratification. However, a number of questions remain
      regarding the use of these biomarkers for screening purposes. In particular,
      appropriate cut-off levels and adjustment for individual patient characteristics
      still need to be established and further cost-effectiveness studies are required
      before screening programs can be undertaken. Given the enormous and increasing
      burden of cardiac failure worldwide, the potential of these biomarkers to
      identify those at greatest risk of the condition, either alone or as part of a
      hybrid screening strategy is of great interest to the cardiology community. The
      aim of this review is to outline evidence behind the argument for screening,
      discuss the remaining barriers to its development and implementation and
      highlight potential areas for future research.

PMID- 23154199
TI  - Educating men about prostate cancer in the workplace.
AB  - Prostate cancer is a common cancer affecting men worldwide. Few men access health
      services with respect to early detection. Workplace health education initiatives
      can promote behavior change in men. A total of 12 in-depth interviews with men
      were conducted in this study to examine how a workplace-based educational
      campaign on prostate cancer influences the knowledge, awareness, and beliefs of
      male workers on screening for prostate cancer. Analyses of interview transcripts
      identified that men had a poor overall knowledge about prostate cancer, its
      screening, and treatment. Participants were receptive to the introduction of
      workplace-based health education initiatives to promote men's health issues but
      recommended an integrated health approach that incorporated information delivered
      by medical professionals, cancer survivors, supplemented with existing patient
      education materials. Further research is required to formally evaluate the impact
      of workplace-based education strategies on men's health. 

PMID- 23154200
TI  - A dialogue on men's health.

PMID- 23154201
TI  - The impact of ovarian stimulation on the expression of candidate reprogramming
      genes in mouse preimplantation embryos.
AB  - Ovarian stimulation with gonadotrophins is an integral part of assisted
      reproductive technologies in human subfertility/infertility treatment. Recent
      findings have associated ovarian stimulation with the increased incidence of
      imprinting disorders in humans as well as defects in genome-wide methylation
      reprogramming and, in particular, imprinting in mice. Here, we present the first
      study that determined the impact of ovarian stimulation on the expression of
      developmentally important reprogramming genes (Apex1, Lig1, Lig3, Mbd2, Mbd3,
      Mbd4, and Polb) in single early mouse morula embryos (16-cell stage). Using
      absolute quantification of mRNA by quantitative real-time PCR, we observed an
      association of ovarian stimulation with a downregulation of mRNAs encoding the
      base excision repair proteins APEX1 and POLB as well as the 5-methyl-CpG-binding
      domain protein MBD3 in individual morula embryos. Whole mount immunofluorescence
      staining of early and late morula embryos with an antibody against APEX1 revealed
      individual embryos with lower protein expression levels after ovarian stimulation
      and a correlation of mRNA expression with protein abundance. Our data argue for a
      negative impact of ovarian stimulation during female gametogenesis and/or early
      embryo development affecting the expression of candidate reprogramming factors.

PMID- 23154202
TI  - The impact of tunneled pleural catheters on the quality of life of patients with
      malignant pleural effusions.
AB  - BACKGROUND: Tunneled pleural catheters (TPC) are used in the management of
      malignant pleural effusions (MPE), but the impact of this palliative procedure on
      patient quality of life (QoL) has not been well described. OBJECTIVES: To
      ascertain the impact of TPCs on symptoms and QoL of patients with recurrent MPE.
      METHODS: Patients with recurrent MPE completed the EORTC QLQ-C30 and LC13 QoL
      questionnaires at baseline, 2 and 14 weeks; FACIT-TS-G(c) treatment satisfaction
      surveys were completed at 14 weeks. RESULTS: A total of 82 patients were
      recruited. Thirty-seven patients (37/82, 45%) died prior to their 14-week follow
      up appointment. Significant improvements in dyspnea at 2 weeks were demonstrated
      with both dyspnea scores (LC13 baseline score 64.1, 2-week score 43.7, mean
      change -20.4, n = 56, p < 0.001; C30 baseline score 78.9, 2-week score 46.6, mean
      change -32.4, n = 68, p < 0.001), as well as with the MRC score (baseline median
      score 4, 2-week score 3, n = 70, p < 0.001). Global health status/QoL was also
      significantly improved at 2 weeks (baseline score 34.1, 2-week score 46.3, mean
      change 12.3, n = 68, p < 0.001). Improvements in cough, fatigue and all
      functional scales were noted at 2 weeks. The improvements in dyspnea and global
      health status/QoL were maintained to 14 weeks in surviving subjects and there was
      further improvement in the MRC score at 14 weeks. Patients who completed the
      FACIT-TS-G survey demonstrated overall satisfaction with TPC treatment.
      CONCLUSIONS: TPCs are associated with a significant improvement in global health
      status, QoL and dyspnea at the 2-week time point in patients with recurrent MPE.

PMID- 23154203
TI  - Long-term changes in the personality and psychopathological profile of opiate
      addicts after nucleus accumbens ablative surgery are associated with treatment
      outcome.
AB  - OBJECTIVE: To investigate the long-term outcome and changes of the personality
      and psychopathological profile of opiate addicts after bilateral stereotactic
      nucleus accumbens (NAc) ablative surgery. METHODS: 60 patients were followed up
      for 5 years and abstinent status and adverse events were evaluated. NAc lesion
      volumes and locations were obtained by postoperative MRI scans. The Chinese
      version of the Eysenck Personality Questionnaire (EPQ-RSC), the Symptom Checklist
      90-Revised (SCL-90-R), the Beck Depression Inventory (BDI), the Yale-Brown
      Obsessive Compulsive Scale (Y-BOCS) and the World Health Organization's Quality
      of Life Questionnaire - Brief Version (WHOQOL-BREF) were administered to the
      patients before and 5 years after the stereotactic surgery. RESULTS: The total
      abstinence rate of all patients in their 5th postoperative year was 47.4%. The
      abstinent patients had a significantly larger lesion volume than the relapsed
      ones, but a larger lesion volume also increased the risk of adverse events. 5
      years after surgery, the abstinent patients showed significant decreases on the
      Psychoticism (EPQ-P) and Neuroticism (EPQ-N) scores by EPQ-RSC, a significant
      decline on the Global Severity Index and the subscores in all 10 dimensions by
      SCL-90-R, significant decreases on the BDI and Y-BOCS scores, and significant
      improvements on the scores of all domains by WHOQOL-BREF, while for the relapsed
      patients, only the subscores of obsessive-compulsive by SCL-90-R and the Y-BOCS
      scores significantly decreased. Postoperative analysis revealed that the
      abstinent patients had a significantly better score than the relapsed ones by
      various instruments, and NAc lesion volumes and locations did not correlate with
      the outcome of any of these instruments. CONCLUSION: The bilateral ablation of
      NAc by stereotactic neurosurgery was a feasible method for alleviating
      psychological dependence on opiate drugs and preventing a relapse. Long-term
      follow-up suggested that surgery can improve the personality and
      psychopathological profile of opiate addicts with a trend towards normal levels,
      provided persistent abstinence can be maintained; relapse, on the other hand, may
      ruin this effect.

PMID- 23154204
TI  - Postural adjustments in catching: on the interplay between segment stabilization
      and equilibrium control.
AB  - The purpose of this study was to investigate postural adjustments in one-handed
      ball catching. Specifically, the functional role of anticipatory postural
      adjustments (APA) during the initial arm raising and subsequent postural
      adjustments (SPA) for equilibrium control and ball-hand impact were scrutinized.
      Full-body kinematics and kinetics allowed an analysis of the mechanical
      consequences of raising up the arm and preparing for ball-hand impact. APA for
      catching were suggested to be for segment stabilization. SPA had a functional
      role for equilibrium control by an inverted pendulum mechanism but were also
      involved in preparing for the impact of the ball on the hand, which was
      illustrated by an increased postural response at the end of the movement. These
      results were compared with raising up the arm in a well-studied reaction-time
      task, for which an additional counter rotation equilibrium mechanism was
      observed. Together, our findings demonstrate that postural adjustments should be
      investigated in relation to their specific functional task constraints, rather
      than generalizing the functional role of these postural adjustments over
      different tasks.

PMID- 23154205
TI  - Adolescent varicocele-is the 20/38 harbinger a durable predictor of testicular
      asymmetry?
AB  - PURPOSE: Part of the management of adolescent varicocele is trying to
      prognosticate who with testicular asymmetry will have catch-up growth with
      observation and who will have persistent asymmetry. We previously reported that
      catch-up growth is rare when peak retrograde flow greater than 38 cm per second
      is associated with 20% or greater asymmetry (ie the 20/38 harbinger). We sought
      to determine if this 20/38 cutoff held true with a larger series, and what peak
      retrograde flow value should be used when 15% instead of 20% asymmetry is chosen
      as the cutoff. MATERIALS AND METHODS: We analyzed patients from our large
      varicocele registry who had undergone at least 2 duplex Doppler ultrasounds and
      had been observed for at least 10 months in the interim. Outcomes were determined
      regarding those who met the 20/38 cutoff and what peak retrograde flow value
      could be used to recommend surgery when 15% to 19.9% asymmetry was included in
      the cutoff value. RESULTS: Of 355 adolescent boys with left varicocele 44 (mean
      age 14.0 years, range 9 to 20) were followed with observation initially and met
      the 20/38 cutoff, while 9 additional patients met the 15/38 cutoff (initial
      asymmetry 15% to 19.9%). When combining both groups, only 3 boys had catch-up
      growth to less than 15% on followup. Thus, 50 of 53 patients did not demonstrate
      catch-up growth after a mean followup of 15.5 months (range 10 to 44).
      CONCLUSIONS: Not only does a peak retrograde flow of greater than 38 cm per
      second hold up for predicting persistent/worsening asymmetry when combined with a
      20% asymmetry cutoff, it also is an excellent predictor of persistent and/or
      worsening asymmetry when combined with a 15% asymmetry cutoff. Therefore, it
      might be unnecessary to follow an adolescent boy with observation who is at or
      above this 15/38 cutoff.

PMID- 23154206
TI  - B7-h1 as a biomarker for therapy failure in patients with favorable histology
      Wilms tumor.
AB  - PURPOSE: A minority of children with Wilms tumor will experience tumor
      recurrence. In a previous pilot study we found an association between expression
      of an immune costimulatory molecule, B7-H1, and tumor recurrence in favorable
      histology Wilms tumor. We sought to verify the prognostic value of B7-H1 as a
      biomarker in favorable histology Wilms tumor. MATERIALS AND METHODS: We performed
      a nested case-control study of tumors from the Fifth National Wilms Tumor Study.
      We randomly selected 44 children unsuccessfully treated (cases) and 49 who were
      successfully treated for favorable histology Wilms tumor (controls). Cases and
      controls were matched based on tumor stage, and the analysis was restricted to
      children who underwent initial resection. We excluded patients with stage IV or V
      disease and those treated with chemotherapy or radiation. Tumor specimens were
      stained for B7-H1 expression. RESULTS: Of the 93 total samples analyzed 60 (65%)
      demonstrated B7-H1 staining, with staining diffusely present in 13 (22%) and
      blastema predominant in 34 (57%). B7-H1 expression was associated with failure of
      initial therapy (p = 0.006). Patients with tumors showing less than 20% B7-H1
      positive cells were at lower risk for treatment failure, while those with tumors
      exhibiting greater than 60% B7-H1 positive cells were at greater risk for
      treatment failure. This association appeared to be independent of tumor stage.
      CONCLUSIONS: B7-H1 expression by favorable histology Wilms tumor is associated
      with an increased risk of failure of initial therapy.

PMID- 23154207
TI  - Primary severe hypospadias: comparison of reoperation rates and parental
      perception of urinary symptoms and cosmetic outcomes among 4 repairs.
AB  - PURPOSE: We compared complication rates, urinary symptoms and cosmetic outcomes
      as perceived by parents of patients undergoing 1 of 4 repairs for proximal
      hypospadias associated with ventral curvature. MATERIALS AND METHODS: A total of
      93 patients underwent hypospadias repair between 2004 and 2010. In patients
      requiring no urethral plate transection the repair consisted of tubularized
      incised plate urethroplasty (26 patients) or onlay island flap urethroplasty
      (31). In patients requiring urethral plate transection the repair consisted of
      onlay island flap on albuginea (18 patients) or 2-stage repair (18).
      Complications were assessed by chart review. A customized questionnaire and the
      Pediatric Penile Perception Score were administered to parents to evaluate their
      perception of urinary symptoms and cosmetic outcomes, respectively. RESULTS:
      After a median followup of 4.5 years (range 2.2 to 8.4) complications developed
      in 21 patients (23%) without any difference among procedures or between patients
      who did and did not require urethral plate transection. Parents of 75 patients
      (80%) participated in the survey without differences among repairs (p = 0.35).
      Reported urinary symptoms were not different among repairs. For Pediatric Penile
      Perception Score the only difference concerned the question about penile length
      (p = 0.03), with the score being significantly better for the techniques
      requiring urethral plate transection (p = 0.05). The 2-stage repair had a
      significantly better score for the question about penile length and overall
      Pediatric Penile Perception Score than all other techniques. CONCLUSIONS: Overall
      complication rates were comparable among repairs and did not increase after
      urethral plate transection. Urinary symptoms as reported by parents were
      comparable among the procedures. Perceived penile length was significantly better
      after urethral plate transection. The 2-stage repair yielded the best cosmetic
      results.

PMID- 23154208
TI  - The specificity of urinary aquaporin 1 and perilipin 2 to screen for renal cell
      carcinoma.
AB  - PURPOSE: Renal cancer is frequently asymptomatic until late stages of the disease
      and it has a poor prognosis when not discovered early. AQP1 and PLIN2 are
      recently discovered, sensitive urine biomarkers of clear cell and papillary
      kidney cancer. We validated these biomarkers in a second cohort of patients and
      determined the effect of common kidney diseases on specificity. MATERIALS AND
      METHODS: Urine samples were obtained from 36 patients with clear cell or
      papillary kidney cancer, 43 controls, 44 patients with documented urinary tract
      infection, 24 diagnosed with diabetic nephropathy and 18 diagnosed with
      glomerulonephritis. Urine levels of AQP1 and PLIN2 normalized to urine creatinine
      were determined by a sensitive, specific Western blot procedure. RESULTS:
      Compared with controls, urine AQP1 and PLIN2 levels in patients with kidney
      cancer were 23-fold and fourfold greater, respectively, and they decreased 83% to
      84% after tumor excision. There was a linear correlation between urine AQP1 and
      PLIN2 levels, and tumor size (each p <0.001). Urine AQP1 and PLIN2 levels in
      patients with kidney cancer were 11 to 23-fold and 17 to 25-fold greater,
      respectively, than in patients with the common kidney diseases. CONCLUSIONS: The
      ability of urine AQP1 and PLIN2 to identify patients with kidney cancer compared
      to controls was validated in a second cohort of patients. Common kidney diseases
      do not adversely increase urine AQP1 and PLIN2 levels or decrease their
      specificity to screen for renal cancer.

PMID- 23154210
TI  - A(2a) adenosine receptor mediates PKA-dependent glutamate release from synaptic
      like vesicles and Ca(2+) efflux from an IP(3)- and ryanodine-insensitive
      intracellular calcium store in astrocytes.
AB  - BACKGROUND/AIMS: The mechanism underlying transmitter release from astrocytes is
      not fully understood. The present study examined A(2a) adenosine receptor
      mediated glutamate release and intracellular Ca(2+) rise in cultured rat
      hippocampal astrocytes. METHODS: Intracellular amino acids were measured with
      HPLC. Glutamate release from astrocytes and intracellular Ca(2+) mobilizations
      were monitored in the NADH imaging, FM1-43 imaging, and fura-2 imaging. The siRNA
      to silence the A(2a) adenosine receptor-targeted gene was constructed and
      transfected into cells. RESULTS: Glutamate was condensed in 'synaptic-like
      vesicle' fractions. In the NADH imaging, CGS21680, an agonist of A2a adenosine
      receptors, increased NADH fluorescent signals, that reflects glutamate release,
      and the effect was inhibited by DMPX, an inhibitor of A(2a) adenosine receptors,
      H-89, a PKA inhibitor, vesicular transport inhibitors, or botulinum toxin-A, an
      exocytosis inhibitor. In the FM1-43 imaging to see vesicular recycling, CGS21680
      decreased FM1-43 fluorescent signals, that was also prevented by DMPX, H-89,
      vesicular transport inhibitors, or botulinum toxin-A. CGS21680 increased
      intracellular Ca(2+) concentrations both in Ca(2+)-containing and -free
      extracellular solution. The Ca(2+) rise was inhibited by DMPX, H-89, or the
      vesicular transport inhibitor brefeldin A, but it was not affected by inhibitors
      for phospholipase C, IP(3) receptor, and ryanodine receptor. CGS21680-induced
      glutamate release and intracellular Ca(2+) rise were prevented by knocking-down
      A(2a) adenosine receptor. CONCLUSION: The results of the present study show that
      A(2a) adenosine receptor/PKA promotes glutamate release from synaptic-like
      vesicles and stimulates Ca(2+) efflux from an IP(3)- and ryanodine-insensitive
      intracellular calcium store.

PMID- 23154211
TI  - Best allograft survival from share-35 kidney donors occurs in middle-aged adults
      and young children-an analysis of OPTN data.
AB  - BACKGROUND: On October 2005, the Organ Procurement and Transplant Network
      implemented a new allocation policy for kidney transplants (KTX) from deceased
      donors (DD) ages <35 years to increase an access to transplantation from young
      donors for pediatric (ages <18 years) recipients, which is known as Share-35
      (S35). However, many of these kidneys were allocated to adult recipients. The
      intent of this study was to analyze the graft outcomes from S35 kidneys in
      pediatric and adult recipients, stratified further by recipient age, to assess if
      recipient age affects the outcome from these presumably ideal kidneys. METHODS:
      The Organ Procurement and Transplant Network database from October 2005 to
      November 2010 involving 18,461 S35-KTX was used to calculate cumulative graft
      survival (CGS), death-censored graft survival, and patient survival using Kaplan
      Meier estimates. The differences between survival curves were tested for
      significance by log-rank method after adjusting for various donor, recipient, and
      transplant-associated variables. RESULTS: With S35 implementation, children
      received a higher proportion of DD ages <35 years. Within the pediatric age
      group, adolescents (ages 13-17 years) had the worst CGS. Among adults, the
      highest CGS was obtained in middle-aged adults, whereas young adults (ages 18-25
      years) showed worse CGS. CGS in young children (ages <12 years) was comparable
      with those in middle-aged adults. In older adults (ages >55 years), CGS was
      lowered by higher patient death rates. CONCLUSIONS: Recipient age affects
      allograft survival from high-quality young DD kidneys, such as S35 kidneys. Best
      survival occurs in middle-aged adults and in children ages <12 years, whereas
      adolescents and young adults do not derive an optimal benefit.

PMID- 23154212
TI  - Influence of delayed graft function and acute rejection on outcomes after kidney
      transplantation from donors after cardiac death.
AB  - BACKGROUND: Delayed graft function (DGF) and acute rejection (AR) exert an
      adverse impact on graft outcomes after kidney transplantation using organs from
      donation after brain-stem death (DBD) donors. Here, we examine the impact of DGF
      and AR on graft survival in kidney transplants using organs from donation after
      cardiac death (DCD) donors. METHODS: We conducted a single-center retrospective
      study of DCD and DBD donor kidney transplants. We compared 1- and 4-year graft
      and patient survival rates, as well as death-censored graft survival (DCGS)
      rates, between the two groups using univariate analysis, and the impact of DGF
      and AR on graft function was compared using multivariate analysis. RESULTS:
      Eighty DCD and 206 DBD donor transplants were analyzed. Median follow-up was 4.5
      years. The incidence of DGF was higher among DCD recipients (73% vs. 27%,
      P<0.001), and AR was higher among DBD recipients (23% vs. 9%, P<0.001). One-year
      and 4-year graft survival rates were similar (DCD 94% and 79% vs. DBD 90% and
      82%). Among recipients with DGF, the 4-year DCGS rate was better for DCD
      recipients compared with DBD recipients (100% vs. 92%, P=0.04). Neither DGF nor
      AR affected the 1-year graft survival rate in DCD recipients, whereas in DBD
      recipients, the 1-year graft survival rate was worse in the presence of DGF (88%
      vs. 96%, P=0.04) and the 4-year DCGS rate was worse in the presence of AR (88%
      vs. 96%, P=0.04). CONCLUSION: Despite the high incidence of DGF, medium-term
      outcomes of DCD kidney transplants are comparable to those from DBD transplants.
      Short-term graft survival from DCD transplants is not adversely influenced by DGF
      and AR, unlike in DBD transplants.

PMID- 23154214
TI  - The early treatment of bradykinin angioedema, a challenge for emergency medicine.

PMID- 23154213
TI  - Altering the dewetting characteristics of ultrathin gold and silver films using a
      sacrificial antimony layer.
AB  - Solid state dewetting of ultrathin films is the most straightforward means of
      fabricating substrate-supported noble metal nanostructures. This assembly process
      is, however, quite inflexible, yielding either densely packed smaller structures
      or widely spaced larger structures. Here, we demonstrate the utility of
      introducing a sacrificial antimony layer between the substrate and noble metal
      overlayer. We observe an agglomeration process which is radically altered by the
      concurrent sublimation of antimony. In stark contrast with conventional
      dewetting, where the thickness of the deposited metal film determines the
      characteristic length scales of the assembly process, it is the thickness of the
      sacrificial antimony layer which dictates both the nanoparticle size and
      interparticle spacing. The result is a far more flexible self-assembly process
      where the nanoparticle size and areal density can be varied widely.
      Demonstrations show nanoparticle areal densities which are varied over four
      orders of magnitude assembled from the identical gold layer thickness, where the
      accompanying changes to nanostructure size see a systematic shift in the
      wavelength of the localized surface plasmon resonance. As a pliable self-assembly
      process, it offers the opportunity to tailor the properties of an ensemble of
      nanostructures to meet the needs of specific applications.

PMID- 23154215
TI  - Recent advances in fluorescent nucleic acid probes for living cell studies.
AB  - Living cell studies can offer tremendous opportunities for biological and disease
      studies. Due to their high sensitivity and selectivity, minimum interference with
      living biological systems, ease of design and synthesis, fluorescent nucleic acid
      probes (FNAPs) have been widely used in living cell studies, such as for
      intracellular detection, cell detection, and cell-to-cell communication. Here, we
      review the general requirements and the recent developments in FNAPs for living
      cell studies. We broadly classify these designs as hybridization probes and
      aptamer probes. For hybridization probes, we describe recently developed designs,
      such as nanomaterial-based and amplification-based hybridization probes. For
      aptamer probes, we discuss four general paradigms that have appeared most
      frequently in the literature: nanomaterial-based, nanomachine-based, cell surface
      anchored and activatable aptamer probe designs in vivo. FNAPs promise to open up
      new and exciting opportunities in biological marks detection for a wide range of
      biological and medical applications.

PMID- 23154217
TI  - Food menus evaluation for most liked products in children from Puna, region of
      Argentina.
AB  - The aim of this study was to investigate the acceptability of varied food menus,
      preferred by children of 11-14 years located at Puna (3500 m.a.s.l.), in young
      urban people. The children drew "the preferred menu" which showed that the
      consumption of vegetables as a main course was comfortable when it was consumed
      in the form of soups and mixed vegetables. However, some imbalances were detected
      when evaluating the percentage of daily nutritional values and the caloric
      distribution of nutrients. Consumer's hedonic scores showed significant
      acceptability to the cheese empanadas, Andean potato cake and Andean mashed
      potato. The free word association test suggested that, because of their
      relationship with culture, the Andean mashed potato, verde potato stew with
      charqui and anchi of apple could be offered as a traditional food. The
      acceptability of meals was largely related to the meals having the highest input
      of energy, fat and carbohydrates but containing the least content of protein and
      dietary fiber.

PMID- 23154216
TI  - Modification of the school cafeteria environment can impact childhood nutrition.
      Results from the Wise Mind and LA Health studies.
AB  - Recent changes in nutrition standards for the National School Lunch and School
      Breakfast Programs assume that modification of the nutritional serving practices
      of school cafeterias will result in improved childhood nutrition in the school
      environment. The primary aim of this paper is to summarize the findings from two
      recent cluster randomized controlled trials (Wise Mind and LA Health) that tested
      the hypothesis that modification of school cafeteria environments, including
      changes in nutrition standards, would yield beneficial changes in childhood
      nutrition and healthy eating in the school lunch environment. A secondary aim was
      to investigate the association of participant characteristics and changes in
      nutrition and healthy eating. A third aim was to investigate the relationships
      between the food intake of children and: (1) foods selected by the children and
      (2) food that was uneaten during the lunch meal (plate waste). The studies used
      similar approaches for modifying the school cafeteria environment and both
      studies used the digital photography method to measure changes in food intake,
      food selection, and plate waste. Both studies reported significant improvements
      in childhood nutrition, and the LA Health study reported improved healthy eating,
      following introduction of the cafeteria modification program in comparison to
      baseline and/or control arms. These studies confirm the hypothesis that
      interventions that modify the school cafeteria environment can beneficially
      impact childhood nutrition.

PMID- 23154218
TI  - Associations between home- and family-related factors and fruit juice and soft
      drink intake among 10- to 12-year old children. The ENERGY project.
AB  - The aim of this study is to investigate associations of family-related factors
      with children's fruit drink/juice and soft drink consumption. A cross-sectional
      survey among 10- to 12-year-old children and their parents in eight European
      countries was conducted to gather this data. Key variables of interest were
      children's self-reported fruit drink/juice and soft drink intake per day
      (outcome) and family-related factors (based on parents' report) related to these
      two behaviors (modeling, automaticity, availability, monitoring, permissiveness,
      negotiating, communicating health beliefs, avoid negative modeling, self
      efficacy, rewarding, and family consumption). 7915 Children (52% girls; mean
      age=11.7 +/- 0.8 years) and 6512 parents (83% women; mean age=41.4 +/- 5.3 years)
      completed the questionnaire. Multilevel regression analyses were used to examine
      the aforementioned associations. Three of the 11 family-related factors
      (modeling, availability, and family consumption) were positively associated with
      children's fruit drink/juice and soft drink intake. Additionally, three family
      related factors (permissiveness, monitoring, and self-efficacy) were solely
      associated with soft drink intake and one family-related factor (communicating
      health beliefs) was related to fruit drink/juice intake. Future interventions
      targeting children's fruit drink/juice and soft drink intake should focus on the
      home environment, parents and their practices, especially on parents' fruit
      drink/juice and soft drink intake and availability of these beverages at home.

PMID- 23154219
TI  - Watching a food-related television show and caloric intake. A laboratory study.
AB  - Television watching has been positively associated with overeating and obesity.
      How popular food-related television shows affects eating behavior has not been
      examined. An experimental study was conducted to examine how exposure to a food
      related television program affects amount and type of food consumed in adults
      (N=80). Participants were randomized to watch a cooking or nature television
      program and were then presented with 800 total calories of chocolate covered
      candies, cheese curls, and carrots. Food was weighed before and after the ad
      libitum eating session to determine amount consumed. After controlling for
      dietary restraint, hunger and food preference, significantly more chocolate
      covered candies were consumed among individuals who watched the cooking program
      compared to the nature program. No significant differences between conditions
      were found for overall caloric intake or for cheese curl or carrot consumption.
      Findings suggest that watching food-related television programs may affect eating
      behavior and has implications for obesity prevention and intervention efforts.

PMID- 23154220
TI  - Comment on "Comparing proteins by their internal dynamics: exploring structure
      function relationships beyond static structural alignments" by C. Micheletti.

PMID- 23154221
TI  - The dynamic view of proteins: comment on "Comparing proteins to their internal
      dynamics: exploring structure-function relationships beyond static structural
      alignments".

PMID- 23154223
TI  - B cells: IL-21 promotes B10 cell population expansion.

PMID- 23154222
TI  - Recognition of CD1d-restricted antigens by natural killer T cells.
AB  - Natural killer T (NKT) cells are innate-like T cells that rapidly produce a
      variety of cytokines following T cell receptor (TCR) activation and can shape the
      immune response in many different settings. There are two main NKT cell subsets:
      type I NKT cells are typically characterized by the expression of a semi
      invariant TCR, whereas the TCRs expressed by type II NKT cells are more diverse.
      This Review focuses on the defining features and emerging generalities regarding
      how NKT cells specifically recognize self, microbial and synthetic lipid-based
      antigens that are presented by CD1d. Such information is vitally important to
      better understand, and fully harness, the therapeutic potential of NKT cells.

PMID- 23154225
TI  - B cell responses: Born to be (a bit) wild.

PMID- 23154226
TI  - Standardization in flow cytometry: correct sample handling as a priority.

PMID- 23154227
TI  - Proposed accelerated FDA approvals for special medical use.

PMID- 23154224
TI  - Eosinophils: changing perspectives in health and disease.
AB  - Eosinophils have been traditionally perceived as terminally differentiated
      cytotoxic effector cells. Recent studies have profoundly altered this simplistic
      view of eosinophils and their function. New insights into the molecular pathways
      that control the development, trafficking and degranulation of eosinophils have
      improved our understanding of the immunomodulatory functions of these cells and
      their roles in promoting homeostasis. Likewise, recent developments have
      generated a more sophisticated view of how eosinophils contribute to the
      pathogenesis of different diseases, including asthma and primary
      hypereosinophilic syndromes, and have also provided us with a more complete
      appreciation of the activities of these cells during parasitic infection.

PMID- 23154228
TI  - What have we learned about the treatment of type 2 diabetes? The evolving
      paradigms.
AB  - Insulin, the first treatment for diabetes, was discovered >90 years ago. Since
      then, many new types of insulin have become available, including analogs that
      more closely mimic the characteristics of endogenous insulin. In addition, oral
      antidiabetes drugs and other types of injectable therapies have been approved for
      the treatment of patients with type 2 diabetes. As newer treatments are approved
      for type 2 diabetes, the choice and-paradoxically-the complexity of treatment
      increases. The potential benefits of all treatment options must be carefully
      balanced against potential adverse events to truly analyze the overall efficacy,
      safety, tolerability, and potential long-term effects. The manner in which
      outcomes are assessed and the methods employed to make such assessments have
      changed over time. This review will address these issues as they are related to
      therapies for type 2 diabetes, including insulin, oral antidiabetes drugs, and
      incretin-based agents.

PMID- 23154229
TI  - Direct thrombin inhibitors: a case indicating benefit from 'plasmapheresis' in
      toxicity: a call for establishing "guidelines" in overdose and to find an
      "antidote"!
AB  - Patient presented with passage of fresh blood mixed with clots per rectum. In the
      ER, she was found to have bright red blood per rectum with clots, with frank
      blood on nasogastric tube. She was on dabigatran for atrial fibrillation and
      aspirin, with intermittent intake of ibuprofen. Vitals were positive for
      orthostatic hypotension. The pertinent findings in the physical examination were
      altered mental status with orientation*1, weak peripheral pulses, irregularly
      irregular heart rate, and bilateral pitting edema 2+ in bilateral lower
      extremities. Patient was intubated and put on mechanical ventilation. A massive
      transfusion protocol was followed. Laboratories and imaging:
      hemoglobin/hematocrit, 7.2/22.1; white blood cells, 7.7, platelet, 210;
      international normalized ratio, 2.5; prothrombin time, 19.2; activated partial
      thromboplastin time, 88.2; CMP was WNL; BNP, 621; fibrinogen, 500 mg/dL.
      Electrocardiogram showed atrial fibrillation with inferolateral ischemia.
      Ultrasonography of the liver and gallbladder showed no acute pathology.
      Echocardiogram showed an EF of 70% with hyperdynamic LV. Patient was transferred
      to the intensive care unit. Dabigatran, aspirin, and nonsteroidal anti
      inflammatory drugs were discontinued, and antihypertensives were held. She was
      given blood and FFPs. Hemoglobin, hematocrit, and coagulation profile was
      monitored every 6 hours. Gastroenterology, general surgery, interventional
      radiology, and hematology services were called stat. IR placed a double-lumen,
      power central venous catheter. In gastroenterology, EGD and colonoscopy was
      performed, which showed active bleed at distal esophagus, stopped with local
      epinephrine. No active bleed seen on colonoscopy. The patient was put on Nexium
      drip. Hematology service recommended thrombin time (>200) and factors 2, 5, 7, 9,
      10-41(l), 80, 68, 48(l), 61. Prothrombin time and activated partial
      thromboplastin time mixing studies were done, which indicated the presence of
      thrombin inhibition. Prothrombin complex concentrate at 50 U/kg was started to
      reverse the effect of dabigatran, and platelets were transfused to reverse the
      effect of aspirin. They also discussed that the half-life of dabigatran being 17
      hours, and the drug would not be toxic at this point, as the patient was already
      24-hour inpatient by now. The hemoglobin trend: 7.4->6.4->8.2->7.5->6.6. At this
      point, the need for further intervention in form of hemodialysis or
      plasmapheresis was considered. The patient was given plasmapheresis and
      hemoglobin and hematocrit stabilized. The patient was kept on continued
      mechanical ventilator support for the night and extubated next day. The
      hemodynamics stabilized and the patient was transferred to the general medical
      floors after 1 day of observation, after extubation.

PMID- 23154230
TI  - The lifeblood of a practice.

PMID- 23154231
TI  - Miniscrew implant-supported rapid maxillary expansion.

PMID- 23154232
TI  - Class II treatment with the smart distalization technique.

PMID- 23154233
TI  - Eruption of a labially impacted canine using a closed-flap technique and
      orthodontic wire traction.

PMID- 23154234
TI  - Miniscrew-retained pontics in growing patients: a biological approach.

PMID- 23154235
TI  - Begg brackets as auxiliaries for thermoformed appliances.

PMID- 23154236
TI  - Genetic variation in the scavenger receptor MARCO and its association with
      chronic obstructive pulmonary disease and lung infection in 10,604 individuals.
AB  - BACKGROUND: MARCO (macrophage receptor with collagenous structure) is a dominant
      receptor for unopsonized particles and bacteria in the lungs. Reduced function of
      this receptor due to genetic variation may be associated with susceptibility to
      chronic obstructive pulmonary disease (COPD) and lung infection. OBJECTIVES: To
      identify novel genetic variants in MARCO that are associated with reduced lung
      function, or increased risk of COPD or lung infection. METHODS: We first screened
      760 individuals with extreme lung phenotypes in a large general population study
      to identify novel variants in the MARCO gene. We next genotyped the entire cohort
      consisting of 10,604 individuals to assess the clinical relevance of these
      variants. RESULTS: We identified 4 novel (R124H, K201N, P303L and G340W) and 5
      previously described (H101Q, F282S, G319V, K387Q and E511D) non-synonymous
      variants. When screening the entire cohort for these variants, we found low minor
      allele frequencies ranging from 0.005 to 5%. None of the individual MARCO
      genotypes were associated with reduced lung function, or risk of COPD or lung
      infection. H101Q heterozygotes had an increased odds ratio for sepsis of 2.2 (95%
      CI: 1.1-4.4) compared to non-carriers, but none of the other MARCO genotypes were
      associated with the risk of sepsis. CONCLUSIONS: We identified 9 non-synonymous
      variants in the MARCO gene and showed that these variants are not major risk
      factors for COPD or lung infection in the Danish population. H101Q heterozygotes
      had increased sepsis risk, but further research is required to confirm this
      finding. This study is the first to examine genetic variants in MARCO and the
      risk of COPD and infections in humans.

PMID- 23154237
TI  - Neuroimmunomodulatory alterations in non-lesional peritoneum close to peritoneal
      endometriosis.
AB  - OBJECTIVES: An imbalance in the ratio of sensory to sympathetic nerve fibre (NF)
      density in peritoneal endometriotic lesions (pEL) has recently been demonstrated
      and leads to the assumption that this preponderance of the sensory pro
      inflammatory milieu is a major cause of pain in endometriosis. Therefore, the
      density of sensory and sympathetic NFs was determined in distal unaffected
      peritoneum of endometriosis patients to be able to detect possible alterations in
      unaffected peritoneum. METHODS: In serial pEL sections (n = 40), lesional and
      matching unaffected peritoneum as well as healthy peritoneum (HP) from patients
      without endometriosis (n = 15) were immunohistochemically analysed to identify
      protein gene product 9.5-, substance P- and tyrosine hydroxylase-positive NFs
      (intact, sensory and sympathetic NFs, respectively). In addition, the amount of
      immune cell infiltrates and the expression of nerve growth factor (NGF) and
      interleukin (IL)-1beta in nerves of peritoneal endometriotic specimens were
      compared to those in the HP. RESULTS: The overall NF density in the non-lesional,
      unaffected peritoneum of endometriosis patients is significantly reduced in
      comparison to both HP and pEL, while sensory NFs remain the same; the sympathetic
      NF density is significantly decreased compared to HP, but is still higher than
      the density close to the pEL. Immune cell infiltrates as well as NGF and IL-1beta
      expression in nerves is significantly elevated in distal unaffected peritoneum in
      comparison to HP. CONCLUSION: The altered NF density in the non-lesional,
      unaffected peritoneum of endometriosis patients suggests new aspects in the
      understanding of the development of endometriosis and pain management in
      endometriosis.

PMID- 23154238
TI  - A widespread and distinctive form of amphipod intersexuality not induced by known
      feminising parasites.
AB  - Intersexuality occurs in a diverse range of animals, and its study offers
      insights into basic reproductive biology. Investigations in amphipods suggest
      intersexuality results from incomplete feminisation caused by sex-distorting
      parasites. It has also been noted that 2 intersex phenotypes occur in males of
      the amphipod Echinogammarus marinus, an external phenotype, in which males
      possess rudimentary brood plates, and an internal phenotype, in which only an
      ovotestis is present. This study examines the relationship between these
      phenotypes and finds their prevalences are independent. In addition, a cross
      species microarray reveals the testicular transcriptomes of the intersex
      phenotypes are distinct from that of normal males and, most crucially, each
      other. Furthermore, the internal intersex phenotype, unlike the external
      phenotype, shows no correlation with infection by known feminising parasites.
      These findings suggest the male intersex phenotypes should not be considered
      stages on a single spectrum of intersexuality. Rather, they support the
      hypothesis that internal and external intersexuality are divergent phenotypes
      with separate causal mechanisms and point to the existence of a distinct and
      geographically widespread form of amphipod intersexuality caused by an unknown
      factor.

PMID- 23154239
TI  - Stimulation of non-neuronal muscarinic receptors enhances chemerin/ChemR23 system
      in dysfunctional endothelial cells.
AB  - AIMS: Endothelial cells play a pivotal role in vascular intimal inflammation
      during cardiovascular diseases. The chemerin/ChemR23 system in endothelial cells
      is one of physiological mechanisms that regulate inflammatory responses. Our
      previous studies indicated that stimulation of non-neuronal muscarinic receptor
      (NNMR) improved endothelial dysfunction. However, the relationship between the
      chemerin/ChemR23 signaling axis and NNMR in endothelial cell is poorly
      understood. Here, we first investigated whether the modulation of
      chemerin/ChemR23 signaling axis is involved in NNMR-mediated endothelial
      protection. MAIN METHODS: Cultured rat aortic endothelial cells (RAECs) were
      used. The ChemR23 protein expression and chemerin secretion were measured using
      Western blot analysis. The gene expression level of ChemR23 was examined with
      reverse transcriptase PCR (RT-PCR). The production of nitric oxide (NO) was
      determined by a nitrate reductase assay kit. KEY FINDINGS: A sharp decline of
      chemerin secretion and ChemR23 protein/gene expression was observed in RAECs
      after exposed to homocysteine at concentration of 0.5 mmol/L. Arecoline (10
      MUmol/L) pretreatment increased ChemR23 protein expression as well as mRNA
      expression, and enhanced the secretion of chemerin. Arecoline could also reverse
      the decreased ChemR23 mRNA expression induced by uric acid, high glucose, or
      oxidized low-density lipoprotein. Furthermore, the modulation of arecoline on
      chemerin/ChemR23 signaling axis was absolutely abolished in the presence of the
      nonselective muscarinic receptors antagonist atropine 1 MUmol/L. Additionally,
      arecoline improved endothelial dysfunction by increasing the reduced NO
      production induced by uric acid, which was blocked by anti-ChemR23 antibody.
      SIGNIFICANCE: The chemerin/ChemR23 signaling axis participates in NNMR-mediated
      protection against endothelial dysfunction in cardiovascular system.

PMID- 23154240
TI  - Analytical surveillance of emerging drugs of abuse and drug formulations.
AB  - Uncontrolled recreational drugs are proliferating in number and variety. Effects
      of long-term use are unknown, and regulation is problematic, as efforts to
      control one chemical often lead to several other structural analogs. Advanced
      analytical instrumentation and methods are continuing to be developed to identify
      drugs, chemical constituents of products, and drug substances and metabolites in
      biological fluids. Several mass spectrometry based approaches appear promising,
      particularly those that involve high resolution chromatographic and mass
      spectrometric methods that allow unbiased data acquisition and sophisticated data
      interrogation. Several of these techniques are shown to facilitate both targeted
      and broad spectrum analyses, the latter of which are often of particular benefit
      when dealing with misleadingly labeled products or assessing a biological matrix
      for illicit drugs and metabolites. The development and application of novel
      analytical approaches such as these will help to assess the nature and degree of
      exposure and risk and, where necessary, inform forensics and facilitate
      implementation of specific regulation and control measures.

PMID- 23154241
TI  - Endoplasmic reticulum stress in HepG2 cells inhibits apolipoprotein A-I
      secretion.
AB  - AIMS: Endoplasmic reticulum (ER) stress modulates gene expression and has been
      implicated in causing dyslipidemias. To determine if ER stress may contribute to
      hypoalphalipoproteinemia through suppression of apo A-I gene expression, human
      hepatoma cell line Hep G2 was treated with ER stress inducers and the changes in
      apo A-I gene expression were compared to albumin gene expression. MAIN METHODS:
      HepG2 cells were treated with tunicamycin (TM) and thapsigargin (TG), two potent
      inducers of ER stress, and apo A-I and albumin protein levels, mRNA levels, and
      promoter activity were measured. ER stress was measured using the ER stress
      responsive alkaline phosphatase assay and by Western blot quantitation of ER
      stress markers such as glucose-regulated protein-78 (GRP-78), phosphorylated Jun
      N-terminal kinase (phospho-JNK), total JNK, phosphorylated eukaryotic initiation
      factor 2 alpha (phospho eIF2alpha), and total eIF2alpha. KEY FINDINGS: TM and TG
      induced ER stress in HepG2 cells and reduced apo A-I and albumin secretion in a
      dose-dependent manner. Intracellular albumin levels increased in cells treated
      with TM and TG while intracellular apo A-I levels decreased. Albumin mRNA and
      albumin gene promoter activity were reduced in proportion to the decrease in
      albumin secreted while changes in the apo A-I mRNA levels and promoter activity
      were modest and did not account for the reduction in apo A-I secretion.
      SIGNIFICANCE: These results indicate that apo A-I secretion is inhibited by ER
      stress possibly by affecting cellular degradation pathways. However, ER stress
      does not affect apo A-I secretion by regulating gene expression.

PMID- 23154242
TI  - Expression of the histamine H4 receptor in dermal and articular tissues.
AB  - Histamine H(4) receptor was identified in 2000 and is the most recently
      identified of the four histamine receptors. It is expressed primarily in immune
      cells and is involved in physiologic functions related to inflammation and
      allergy. Recently, the H(4) receptor was highlighted as a promising therapeutic
      target in atopic dermatitis, asthma, and chronic arthritis. In fact, some H(4)
      receptor antagonists have reached clinical trials for the treatment of asthma,
      atopic dermatitis, and allergic rhinitis. Based on an initial assessment of
      distribution, the H(4) receptor has been referred to as the histamine receptor of
      the hematopoietic system. However, the H(4) receptor has also been implicated in
      the regulation of other non-hematopoietic systems. Here, we review the expression
      and function of the H(4) receptor with a focus on dermal and articular tissues.
      In skin, the H(4) receptor is expressed in both the epidermis and dermis, with
      stronger receptor expression in the epidermis. In articular tissue, H(4) receptor
      expression has been detected in synovial cells. Chondrocytes, a major cell
      sources for cartilage tissue engineering, also express the H(4) receptor. Further
      understanding of the functions of H(4) receptors in non-hematopoietic cells might
      lead to novel treatments for diseases with unmet needs.

PMID- 23154243
TI  - Retraction: Development of paclitaxel loaded NIPAAm/VP polymeric nanoparticles
      for efficacy enhancement against human cancer therapy.
AB  - This article has been withdrawn at the request of the author(s) and/or editor.
      The Publisher apologizes for any inconvenience this may cause. The full Elsevier
      Policy on Article Withdrawal can be found at
      http://www.elsevier.com/locate/withdrawalpolicy.

PMID- 23154244
TI  - Agmatine promotes the migration of murine brain endothelial cells via multiple
      signaling pathways.
AB  - AIMS: The combination of adhesion and migration of endothelial cells (ECs) is an
      integral process for evolution, organization, repair and vessel formation in
      living organisms. Agmatine, a polycationic amine existing in brain, has been
      investigated to exert neuroprotective effects. Up to date, there are no studies
      reporting that agmatine modulates murine brain endothelial (bEnd.3) cells
      migration. In the present study, we intend to investigate the role of agmatine in
      bEnd.3 cells migration and the molecular mechanism mediating this action. MAIN
      METHODS: The effect of agmatine on the bEnd.3 cells migration was examined by
      migration assay, and the mechanism involved for this effect was investigated by
      western blot analysis and NO contents measurements. KEY FINDINGS: Agmatine
      treatment (50, 100 and 200 MUM) significantly accelerated bEnd.3 cells migration
      in a concentration-dependent manner. Western blotting revealed that agmatine
      treatment significantly induced vascular endothelial growth factor (VEGF), VEGF
      receptor 2 (Flk-1/KDR or VEGFR2), phosphatidylinositol 3-kinase (PI3K),
      Akt/protein kinase B (also known as PKB, PI3K downstream effector protein),
      endothelial nitric oxide synthase (eNOS) nitric oxide (NO; product by eNOS) and
      intercellular adhesion molecule 1 (ICAM-1) expressions during bEnd.3 cells
      migration. The expression of ICAM-1 and migration of bEnd.3 cells, induced by
      agmatine, were significantly attenuated by treatment of wortmannin, a specific
      PI3K inhibitor. SIGNIFICANCE: Taken together, we provide the first evidence that
      activation of VEGF/VEGFR2 and the consequential PI3K/Akt/eNOS/NO/ICAM-1 signaling
      pathways are serial events, through which the treatment of agmatine could lead to
      bEnd.3 cells migration.

PMID- 23154245
TI  - Hydroxychloroquine-induced cardiomyopathy that presented as pulmonary
      hypertension: a newly noted complication.
AB  - We examined a 63-year-old woman with progressive dyspnea. Two years prior to
      admission to our hospital, she had been diagnosed with rheumatoid arthritis and
      treated with hydroxychloroquine (HCQ) with a cumulative dose of 164 g. In
      addition, 2 months earlier, she had been diagnosed with connective tissue disease
      related pulmonary artery hypertension. We performed an electrocardiogram and
      noted complete atrioventricular block. A transthoracic echocardiogram showed
      pulmonary hypertension. Due to the unclear nature of the pulmonary hypertension,
      we performed cardiac catheterization and right ventricular endomyocardial biopsy.
      Cardiac catheterization revealed that pulmonary hypertension was due to left
      ventricular dysfunction. Electron microscopy of the cardiac biopsy demonstrated a
      curvilinear body, diagnostic of HCQ toxicity. Thus, we diagnosed pulmonary
      hypertension owing to left heart disease and complete atrioventricular block that
      resulted from HCQ toxicity. Insertion of a permanent pacemaker and
      discontinuation of HCQ dramatically improved the disease state. This is the first
      report of this type of cardiac complication with HCQ; it raises the awareness
      that HCQ may cause cardiac complications despite a small cumulative dose relative
      to doses reported in other cases. Furthermore, we emphasize that cardiac
      catheterization played a critical role in the differential diagnosis from
      pulmonary hypertension associated with connective tissue disease.

PMID- 23154247
TI  - Dermatofibrosarcoma protuberans in childhood.
AB  - Dermatofibrosarcoma protuberans (DFSP) is a fibrohistiocytic tumor of
      intermediate malignancy that is very rare in childhood. Only 6% of these tumors
      present in children. Clinical diagnosis is very difficult in the early stages of
      disease, but to ensure appropriate treatment it is important to identify DFSP as
      early as possible and rule out benign conditions that are more common at this
      age. The clinical presentation and histopathologic and molecular characteristics
      of DFSP are similar in children and adults. Clinical diagnosis is, however, more
      difficult in children and requires a high degree of suspicion. The absence of
      characteristic features and the rarity of this tumor explain why diagnosis is
      often delayed. Complete surgical excision of the tumor is very important to
      reduce the risk of recurrence. This article presents a review of current
      knowledge about the management of DFSP in children and examines the latest
      treatment options.

PMID- 23154246
TI  - "Right time, right place" health communication on Twitter: value and accuracy of
      location information.
AB  - BACKGROUND: Twitter provides various types of location data, including exact
      Global Positioning System (GPS) coordinates, which could be used for
      infoveillance and infodemiology (ie, the study and monitoring of online health
      information), health communication, and interventions. Despite its potential,
      Twitter location information is not well understood or well documented, limiting
      its public health utility. OBJECTIVE: The objective of this study was to document
      and describe the various types of location information available in Twitter. The
      different types of location data that can be ascertained from Twitter users are
      described. This information is key to informing future research on the
      availability, usability, and limitations of such location data. METHODS: Location
      data was gathered directly from Twitter using its application programming
      interface (API). The maximum tweets allowed by Twitter were gathered (1% of the
      total tweets) over 2 separate weeks in October and November 2011. The final
      dataset consisted of 23.8 million tweets from 9.5 million unique users.
      Frequencies for each of the location options were calculated to determine the
      prevalence of the various location data options by region of the world, time
      zone, and state within the United States. Data from the US Census Bureau were
      also compiled to determine population proportions in each state, and Pearson
      correlation coefficients were used to compare each state's population with the
      number of Twitter users who enable the GPS location option. RESULTS: The GPS
      location data could be ascertained for 2.02% of tweets and 2.70% of unique users.
      Using a simple text-matching approach, 17.13% of user profiles in the 4
      continental US time zones were able to be used to determine the user's city and
      state. Agreement between GPS data and data from the text-matching approach was
      high (87.69%). Furthermore, there was a significant correlation between the
      number of Twitter users per state and the 2010 US Census state populations (r >=
      0.97, P < .001). CONCLUSIONS: Health researchers exploring ways to use Twitter
      data for disease surveillance should be aware that the majority of tweets are not
      currently associated with an identifiable geographic location. Location can be
      identified for approximately 4 times the number of tweets using a straightforward
      text-matching process compared to using the GPS location information available in
      Twitter. Given the strong correlation between both data gathering methods, future
      research may consider using more qualitative approaches with higher yields, such
      as text mining, to acquire information about Twitter users' geographical
      location.

PMID- 23154248
TI  - Carbon dioxide laser treatment of epidermal nevi: response and long-term follow
      up.
AB  - BACKGROUND AND OBJECTIVES: Epidermal nevi, which are benign skin growths, have
      been treated using a range of approaches, with varying results. Topical
      treatments are ineffective and, while surgical excision is a more definitive
      treatment, it causes scar formation. In recent decades, epidermal nevi have been
      treated with various types of laser therapy. We describe our experience with the
      use of carbon dioxide (CO(2)) laser therapy to treat epidermal nevi and
      inflammatory linear verrucous epidermal nevi (ILVEN). PATIENTS AND METHODS:
      Twenty patients (15 with epidermal nevi and 5 with ILVEN) underwent CO(2) laser
      treatment at our hospital between 2002 and 2010. RESULTS: Response was good (>50%
      reduction in lesion size) in 50% of cases and excellent (>75% reduction) in 30%.
      A greater resistance to treatment was observed in patients with ILVEN (only 40%
      had a good response). Long-term follow-up (at least 18 months) showed a
      recurrence rate of 30%. The side effects were hypopigmentation (25% of patients)
      and scarring (20%). CONCLUSIONS: We consider CO(2) laser therapy to be the
      treatment of choice for epidermal nevi as it is well tolerated and has proven to
      be safe and effective in the long term. While the response in patients with ILVEN
      was limited, CO(2) laser therapy might be a good option for selected cases or for
      palliative treatment since no other treatments have yet proven effective in this
      setting.

PMID- 23154249
TI  - Hyperkeratosis and scaling in identical twins.

PMID- 23154250
TI  - Dermatosis neglecta or terra firma-forme dermatosis.

PMID- 23154251
TI  - Managing adverse effects and complications in completing treatment for hepatitis
      C virus infection.
AB  - The addition of direct-acting antivirals (DAAs) to hepatitis C virus (HCV)
      treatment regimens has made treatment more effective and patient management more
      complex. Shepherding patients through a full course of HCV therapy requires
      motivation and involvement on the part of the patient and the physician. Indeed,
      physician inexperience and lack of confidence in guiding patients through the
      challenges of treatment appears to be a primary reason for early discontinuation
      of therapy. Among the many complications of HCV treatment that must be managed
      efficiently and effectively are depression and other psychiatric disorders;
      hematologic abnormalities including DAA- and ribavirin-associated anemia and
      peginterferon alfa-associated neutropenia and thrombocytopenia; rash and drug
      eruptions, including telaprevir-associated rash; and weight loss. Practical
      considerations in management of these common complications are offered. This
      article summarizes a presentation by Kenneth E. Sherman, MD, PhD, at the IAS-USA
      live continuing medical education course held in New York in June 2012.

PMID- 23154252
TI  - Cardiovascular risk and dyslipidemia management in HIV-infected patients.
AB  - HIV infection and antiretroviral therapy each appear to increase cardiovascular
      disease risk. Increased risk may be attributable to the inflammatory effects of
      HIV infection and dyslipidemia associated with some antiretroviral agents. The
      prevalence of cardiovascular disease is increasing as patients live longer, age,
      and acquire traditional coronary heart disease (CHD) risk factors. In general,
      any additional cardiovascular risk posed by HIV infection or antiretroviral
      therapy is of potential concern for patients who are already at moderate or high
      risk for CHD. Long-term and well-designed studies are needed to more accurately
      ascertain to what degree HIV infection and antiretroviral therapy affect long
      term cardiovascular disease risk. Management of dyslipidemia to reduce CHD risk
      in HIV-infected patients is much the same as in the general population, with the
      cornerstone consisting of statin therapy and lifestyle interventions. Smoking
      cessation is a major step in reducing CHD risk in those who smoke. This article
      summarizes a presentation by James H. Stein, MD, at the IAS-USA live continuing
      medical education activity held in New York City in March 2012.

PMID- 23154253
TI  - Syphilis negatively influences the response to hepatitis C virus treatment in an
      HIV-infected patient.

PMID- 23154254
TI  - Beyond telaprevir and boceprevir: resistance and new agents for hepatitis C virus
      infection.
AB  - The addition of the hepatitis C virus (HCV) protease inhibitors telaprevir and
      boceprevir to peginterferon alfa with ribavirin therapy has increased cure rates
      in HCV infection. Numerous other direct-acting antivirals (DAAs) are in advanced
      stages of development, including next-generation protease inhibitors,
      nonstructural protein (NS) 5A inhibitors, and nonnucleoside and nucleos(t)ide
      NS5B polymerase inhibitors. The classes have different potencies, different
      resistance mutation profiles, and different barriers to the emergence of
      resistance. A comprehensive table of resistance mutations for classes of DAAs is
      presented. Numerous combinations of DAAs with or without ribavirin have been
      evaluated in early studies of interferon alfa-free regimens, with results
      indicating that cure is indeed possible with such therapy and suggesting that
      identification of regimens that could produce cure in the majority of patients
      may occur within the foreseeable future. This article summarizes a presentation
      by David L. Wyles, MD, at the IAS-USA live continuing medical education activity
      held in New York in June 2012.

PMID- 23154257
TI  - Virology: giant viruses--movers and shakers.

PMID- 23154258
TI  - Immunology: splice-tailored to fit the bug.

PMID- 23154260
TI  - Structural vaccinology starts to deliver.
AB  - Following the impact of the genomics revolution on vaccine research and the
      development of reverse vaccinology, it was predicted that another new approach,
      structure-based antigen design, would become a driving force for vaccine
      innovation. Now, 5 years on, there are several examples of how structure-based
      design, or structural vaccinology, can deliver new vaccine antigens that were not
      possible before. Here, we discuss some of these examples and the contribution of
      structural vaccinology to our understanding of the protective epitopes of
      important bacterial and viral pathogens.

PMID- 23154263
TI  - Add-on-therapy with bevacizumab in children and adolescents with poor prognosis
      non-CNS solid tumors.
AB  - Bevacizumab is increasingly being used in adult patients with cancer and children
      with central nervous system (CNS) tumors. Little, however, is known about the
      efficacy, risks, and benefits of bevacizumab administration in non-CNS tumors of
      childhood. The aim of the present study was to report on bevacizumab administered
      as add-on-therapy for poor prognosis non-CNS solid tumors of childhood and
      adolescence, including a prospective evaluation of side effects of bevacizumab.
      Seven patients (female: n = 5; median age, 14.5 years) with relapsed (n = 4) or
      primary metastatic (n = 3) solid non-CNS tumors received bevacizumab at 5-10
      mg/kg body weight intravenously every 2-3 weeks. Assessment of cardiac function,
      thyroid hormone levels, urine analysis, and radiographic responses were carried
      out every 3 months. The median time of bevacizumab treatment was 10 (range, 5-17)
      months. Patients received a median of 16 (range, 10-38) bevacizumab infusions.
      With a median follow-up of 25 (range, 13-38) months, five patients relapsed after
      7-25 months and three of them died. Two patients are still in complete remission
      for 31 and 32 months, respectively. Fraction shortening decreased in two
      patients. Bevacizumab was associated with new-onset increase in basal thyroid
      stimulating hormone (n = 3), mild proteinuria/hematuria (n = 5), intermittent
      hypertension (n = 2), hypertension requiring antihypertensive medication (n = 3),
      and epistaxis (n = 2). In two patients, therapy with bevacizumab was terminated
      because of side effects. Selected patients with relapsed or primary metastatic
      solid non-CNS tumors of childhood and adolescence might benefit from add-on
      therapy with bevacizumab. Although the side effects were usually mild, cardiac
      monitoring seems to be essential during and after the administration of
      bevacizumab.

PMID- 23154264
TI  - Impact of 3D conformal radiotherapy on lung function of patients with lung
      cancer: a prospective study.
AB  - BACKGROUND: The development of three-dimensional conformal radiotherapy (3D-RT)
      has enabled the restriction of the dose to normal lung, limiting radiation
      induced lung injury. OBJECTIVES: This study was designed to describe the time
      course of lung function until 7.5 months after 3D-RT in patients with lung
      cancer, and assess the relationship between lung function changes and dose-volume
      histogram (DVH) analysis or computed tomography scan changes. Radiation doses
      were optimized according to recent guidelines. METHODS: Sixty-five lung cancer
      patients treated with 3D-RT agreed to participate in this prospective, hospital
      based study. Lung volumes, forced expiratory volume in 1 s (FEV1) and diffusing
      capacity of the lung for carbon monoxide (DLCO) were measured before radiotherapy
      (RT), 10 weeks, 4 and 7.5 months after the beginning of 3D-RT. RESULTS: Eleven
      lung cancer patients (17%) developed grade 2-3 respiratory symptoms after RT. At
      7.5 months, vital capacity (VC) was 96 +/- 2%, total lung capacity (TLC) 95 +/-
      2%, FEV1 93 +/- 2% and DLCO 90 +/- 2% of the initial value. Only 15% of patients
      showed pulmonary function reduction > 20%. Patients with FEV1 or DLCO < 60%
      before RT did not show significant changes after RT. There were weak correlations
      between reduction of VC, TLC, FEV1 or DLCO and radiation dosimetric parameters
      and between reduction of VC or FEV1 and radiation-induced pneumonitis images.
      CONCLUSIONS: In lung cancer, the reduction of lung function within 7.5 months
      after 3D-RT was small and correlated, albeit weakly, with DVH parameters.
      Patients with initially impaired lung function showed tiny changes in spirometry
      and DLCO values.

PMID- 23154265
TI  - The role of intraoperative fluid optimization using the esophageal Doppler in
      advanced gynecological cancer: early postoperative recovery and fitness for
      discharge.
AB  - OBJECTIVE: To determine the effect of fluid optimization using esophageal Doppler
      monitoring (EDM) when compared to standard fluid management in women who undergo
      major gynecological cancer surgery and whether its use is associated with reduced
      postoperative morbidity. METHODS: From January 2009 to December 2010, women
      undergoing laparotomy for pelvic masses or uterine cancer had either fluid
      optimization using intraoperative EDM or standard fluid replacement without using
      EDM. Cases were selected from 2 surgeons to control for variability in surgical
      practice. Demographic and surgical details were collected prospectively.
      Univariate and multivariate analyses were performed to quantify the association
      between the use of EDM with "early postoperative recovery" and "early fitness for
      discharge." RESULTS: A total of 198 women were operated by the 2 prespecified
      surgeons; 79 women had fluid optimization with EDM, whereas 119 women had
      standard anesthetic care. The use of ODM was associated with earlier
      postoperative recovery (adjusted odds ratio, 2.83; 95% confidence interval, 1.20
      6.68; P = 0.02) and earlier fitness for discharge (adjusted odds ratio, 2.81; 95%
      confidence interval, 1.01-7.78; P = 0.05). Women with advanced-stage disease in
      the "EDM" group resumed oral diet earlier than women in the "no EDM" group
      (median, 1 day vs 2 days; P = 0.02). These benefits with EDM did not extend to
      women with early-stage disease/benign/borderline tumors. No significant
      difference in postoperative complications was noted. CONCLUSIONS: Intraoperative
      fluid optimization with EDM in women with advanced gynecological cancer may be
      associated with improved postoperative recovery and early fitness for discharge.
      Studies with adequate power are needed to investigate its role in reducing
      postoperative complications.

PMID- 23154261
TI  - Microbial life in the phyllosphere.
AB  - Our knowledge of the microbiology of the phyllosphere, or the aerial parts of
      plants, has historically lagged behind our knowledge of the microbiology of the
      rhizosphere, or the below-ground habitat of plants, particularly with respect to
      fundamental questions such as which microorganisms are present and what they do
      there. In recent years, however, this has begun to change. Cultivation
      independent studies have revealed that a few bacterial phyla predominate in the
      phyllosphere of different plants and that plant factors are involved in shaping
      these phyllosphere communities, which feature specific adaptations and exhibit
      multipartite relationships both with host plants and among community members.
      Insights into the underlying structural principles of indigenous microbial
      phyllosphere populations will help us to develop a deeper understanding of the
      phyllosphere microbiota and will have applications in the promotion of plant
      growth and plant protection.

PMID- 23154262
TI  - Animal models for HIV/AIDS research.
AB  - The AIDS pandemic continues to present us with unique scientific and public
      health challenges. Although the development of effective antiretroviral therapy
      has been a major triumph, the emergence of drug resistance requires active
      management of treatment regimens and the continued development of new
      antiretroviral drugs. Moreover, despite nearly 30 years of intensive
      investigation, we still lack the basic scientific knowledge necessary to produce
      a safe and effective vaccine against HIV-1. Animal models offer obvious
      advantages in the study of HIV/AIDS, allowing for a more invasive investigation
      of the disease and for preclinical testing of drugs and vaccines. Advances in
      humanized mouse models, non-human primate immunogenetics and recombinant
      challenge viruses have greatly increased the number and sophistication of
      available mouse and simian models. Understanding the advantages and limitations
      of each of these models is essential for the design of animal studies to guide
      the development of vaccines and antiretroviral therapies for the prevention and
      treatment of HIV-1 infection.

PMID- 23154266
TI  - Reduced expression of DKK3 is associated with adverse clinical outcomes of
      uterine cervical squamous cell carcinoma.
AB  - OBJECTIVE: The aim of this study was to assess the expression of DKK3 protein and
      its target, beta-catenin, in uterine cervical squamous cell carcinoma and to
      determine potential clinical correlations. MATERIALS AND METHODS: Six carcinoma
      in-situ (CIS) tissues and 88 invasive cervical cancer tissues were included in
      the study. Twenty-two normal cervical tissues and one gastric cancer tissue were
      used as controls. The expression of DKK3 and beta-catenin proteins was evaluated
      by immunohistochemical analysis. Clinical and pathological parameters were
      obtained from medical records. Survival data were estimated using Kaplan-Meier
      estimates and compared with a log-rank test. Multivariate analysis was performed
      using the Cox regression method. RESULTS: DKK3 was predominantly present in the
      cytoplasm. Beta-catenin was observed only on the cellular membrane of both normal
      and cancer cells in contrast to earlier reports, in which beta-catenin was
      localized to the cytoplasm and nucleus of cancer cells. The expressions of beta
      catenin and DKK3 were not correlated. Three of 6 CIS (50%) and 57 of 88 invasive
      cancer specimens (64.8%) had lower DKK3 expression than normal controls. DKK3
      expression was decreased in a stage-dependent manner (P = 0.021). The patients
      with low expression of DKK3 were older than those with high expression of DKK3 (P
      < 0.01). Moreover, the patients with low DKK3 expression had a significantly
      lower 5-year disease-free survival rate than those with high DKK3 expression (P =
      0.026). A multivariate analysis showed that International Federation of
      Gynecology and Obstetrics clinical stage and parametrial involvement were
      independent prognostic factors. CONCLUSION: Decreased DKK3 expression was
      associated with advanced International Federation of Gynecology and Obstetrics
      clinical stages and was predictive of lower disease-free survival in patients
      with cervical squamous cell carcinoma. DKK3 may be implicated in cervical
      carcinogenesis through a beta-catenin-independent mechanism.

PMID- 23154267
TI  - Starving tumors:  inhibition of glycolysis reduces viability of human endometrial
      and ovarian cancer cells and enhances antitumor efficacy of GnRH receptor
      targeted therapies.
AB  - OBJECTIVE: Increased glycolysis for energy production is necessary for survival
      of tumor cells and thus represents a selective therapeutic target. We have
      analyzed in vitro whether inhibition of glycolysis can reduce the viability of
      human endometrial and ovarian cancer cells and whether it can enhance the
      antitumor efficacy of GnRH receptor-targeted therapies. MATERIALS AND METHODS:
      Cell viability of ovarian and endometrial cancer cells treated without or with
      glycolysis inhibitor 2-Deoxy-D-Glucose (2DG) alone or in combination with GnRH-II
      antagonist [Ac-D2Nal(1), D-4Cpa(2), D-3Pal(3,6)(8),Leu, D-Ala(10)]GnRH-II or with
      cytotoxic GnRH-I agonist AEZS-108 (AN-152) was measured using alamar blue assay.
      Induction of apoptosis was analyzed using TUNEL assay and quantified by
      measurement of loss of mitochondrial membrane potential. Apoptotic signaling was
      measured by quantification of activated caspase-3 by using the Western blot
      technique. RESULTS: Treatment of endometrial and ovarian cancer cells with
      glycolysis inhibitor 2DG resulted in a significant decrease of cell viability and
      a significant increase of apoptosis. Treatment with 2DG in combination with the
      GnRH-II antagonist or with AEZS-108 resulted in a significant reduced viability
      compared with single-agent treatments. The observed reduction in viability was
      due to induction of apoptosis. Also for apoptosis induction, a significant
      stronger effect in the case of cotreatments compared with single-agent treatments
      could be observed. These additive effects could be correlated to increased
      activation of caspase-3. CONCLUSIONS: The glycolytic phenotype of human
      endometrial and ovarian cancer cells can be targeted for therapeutic
      intervention. In addition, cotreatment of a glycolysis inhibitor with GnRH
      receptor-targeted therapies might be a suitable therapy for GnRH receptor
      positive human endometrial and ovarian cancers.

PMID- 23154268
TI  - Prognostic significance of cell cycle- and invasion-related molecular markers and
      genomic instability in primary carcinoma of the vagina.
AB  - OBJECTIVE: This study aimed to analyze the prognostic value of DNA content and
      biological markers for cell cycle regulation and invasion in primary carcinoma of
      the vagina (PCV). MATERIAL AND METHODS: Seventy-two consecutive patients with
      PCV, categorized as short-term (<= 2 years) and long-term (>= 8 years) survivors,
      were evaluated for DNA content by image cytometry, and for expression of p53,
      p21, cyclin A, Ki67, E-cadherin, and laminin-5gamma2 chain by
      immunohistochemistry. The relationship between these biological markers and
      histopathological and clinical parameters was assessed. RESULTS: All PCV showed
      aneuploid DNA content. Most of the PCV patients showed no overexpression of p53
      and high expression of p21, cyclin A, and Ki67. Loss or underexpression of E
      cadherin was found in 94% (68/72) of PCV patients, and all patients showed
      immunopositivity for the laminin-5gamma2 chain. Tumors with a vaginal
      longitudinal location in the lower third or in the entire vagina more often had
      overexpression of p53, high expression of Ki67 (P = 0.044), and underexpression
      of E-cadherin (P = 0.038), than tumors confined only to the upper third.
      Overexpression of p53 was significantly associated with short-term survival in
      the univariate analysis, but not in the multivariate analysis adjusted for age at
      diagnosis and tumor size. CONCLUSIONS: The expression level of some markers was
      related to tumor location, which might be indicative of different genesis.
      Overexpression of p53 was associated with short-term survival, but the only
      independent predictors of survival were age at diagnosis and tumor size.

PMID- 23154269
TI  - Molten-droplet synthesis of composite CdSe hollow nanoparticles.
AB  - Many colloidal synthesis routes are not scalable to high production rates,
      especially for nanoparticles of complex shape or composition, due to precursor
      expense and hazards, low yields, and the large number of processing steps. The
      present work describes a strategy to synthesize hollow nanoparticles (HNPs) out
      of metal chalcogenides, based on the slow heating of a low-melting-point metal
      salt, an elemental chalcogen, and an alkylammonium surfactant in octadecene
      solvent. The synthesis and characterization of CdSe HNPs with an outer diameter
      of 15.6 +/- 3.5 nm and a shell thickness of 5.4 +/- 0.9 nm are specifically
      detailed here. The HNP synthesis is proposed to proceed with the formation of
      alkylammonium-stabilized nano-sized droplets of molten cadmium salt, which then
      come into contact with dissolved selenium species to form a CdSe shell at the
      droplet surface. In a reaction-diffusion mechanism similar to the nanoscale
      Kirkendall effect it is speculated that the cadmium migrates outwardly through
      this shell to react with more selenium, causing the CdSe shell to thicken. The
      proposed CdSe HNP structure comprises a polycrystalline CdSe shell coated with a
      thin layer of amorphous selenium. Photovoltaic device characterization indicates
      that HNPs have improved electron transport characteristics compared to standard
      CdSe quantum dots, possibly due to this selenium layer. The HNPs are colloidally
      stable in organic solvents even though carboxylate, phosphine, and amine ligands
      are absent; stability is attributed to octadecene-selenide species bound to the
      particle surface. This scalable synthesis method presents opportunities to
      generate hollow nanoparticles with increased structural and compositional
      variety.

PMID- 23154270
TI  - The M235T polymorphism in the angiotensinogen gene and heart failure: a meta
      analysis.
AB  - BACKGROUND: The aim of the present study was to assess the association between
      M235T polymorphism and heart failure using a meta-analysis. METHODS: A literature
      search of Google Scholar, PubMed, the Cochrane Library and the China National
      Knowledge Infrastructure database (January 1990-April 2012) was performed for
      relevant studies. Statistical analyses were carried out using the Stata 12.0 to
      combine all the relevant studies. Summary odds ratios (ORs) and 95% confidence
      intervals (95% CIs) were calculated in a fixed-effects model and a random-effects
      model when appropriate. The pooled ORs were performed under the allelic contrast
      (T vs M), the dominant (TT + MT vs. MM) and the recessive models (TT vs MT + MM).
      Begg's test was used to measure publication bias. RESULTS: A total of six case
      control studies including 842 patients and 1054 controls were enrolled in this
      meta-analysis. Overall, there was a significant association between
      angiotensinogen (AGT) gene M235T polymorphism and risk of heart failure in the
      subgroup analysis under the allelic contrast (T vs M: OR = 1.48, 95% CI: 1.04
      2.11) and the dominant model (TT+MT vs MM: OR=1.67, 95% CI: 1.13-2.46) in the
      Caucasian population. CONCLUSIONS: The current meta-analysis suggests that M235T
      polymorphism might be associated with increased risk of heart failure in
      Caucasians.

PMID- 23154271
TI  - Serum uric acid in patients with Parkinson's disease and vascular parkinsonism: a
      cross-sectional study.
AB  - BACKGROUND: Elevation of serum uric acid (UA) is correlated with a decreased risk
      of Parkinson's disease (PD); however, the association and clinical relevance of
      serum UA levels in patients with PD and vascular parkinsonism (VP) are unknown.
      OBJECTIVE: We performed a cross-sectional study of 160 Chinese patients with PD
      and VP to determine whether UA levels in patients could predict the outcomes.
      METHODS: Serum UA levels were divided into quartiles and the association between
      UA and the severity of PD or VP was investigated in each quartile. RESULTS: The
      serum levels of UA in PD were significantly lower than those in normal subjects
      and VP. The serum UA levels in PD patients were significantly correlated with
      some clinical parameters. Strong correlations were observed in male PD patients,
      but significant correlations were observed only between UA and the non-motor
      symptoms (NMS) of burden of sleep/fatigue and mood in female PD patients. PD
      patients in the lowest quartile of serum UA levels had significant correlations
      between UA and the unified Parkinson's disease rating scale, the modified Hoehn
      and Yahr staging scale and NMS burden for attention/memory. CONCLUSION: Our
      findings support the hypothesis that subjects with low serum UA levels may be
      more prone to developing PD and indicate that the inverse relationship between UA
      and severity of PD was robust for men but weak for women. Our results strongly
      imply that either low serum UA level is a deteriorative predictor or that serum
      UA level serves as an indirect biomarker of prediction in PD but not in VP
      patients.

PMID- 23154272
TI  - Synthesis and modifications of phosphinic dipeptide analogues.
AB  - Pseudopeptides containing the phosphinate moiety (-P(O)(OH)CH(2)-) have been
      studied extensively, mainly as transition state analogue inhibitors of
      metalloproteases. The key synthetic aspect of their chemistry is construction of
      phosphinic dipeptide derivatives bearing appropriate side-chain substituents.
      Typically, this synthesis involves a multistep preparation of two individual
      building blocks, which are combined in the final step. As this methodology does
      not allow simple variation of the side-chain structure, many efforts have been
      dedicated to the development of alternative approaches. Recent achievements in
      this field are summarized in this review. Improved methods for the formation of
      the phosphinic peptide backbone, including stereoselective and multicomponent
      reactions, are presented. Parallel modifications leading to the structurally
      diversified substituents are also described. Finally, selected examples of the
      biomedical applications of the title compounds are given.

PMID- 23154273
TI  - Nucleoside triphosphates--building blocks for the modification of nucleic acids.
AB  - Nucleoside triphosphates are moldable entities that can easily be functionalized
      at various locations. The enzymatic polymerization of these modified triphosphate
      analogues represents a versatile platform for the facile and mild generation of
      (highly) functionalized nucleic acids. Numerous modified triphosphates have been
      utilized in a broad palette of applications spanning from DNA-tagging and 
      labeling to the generation of catalytic nucleic acids. This review will focus on
      the recent progress made in the synthesis of modified nucleoside triphosphates as
      well as on the understanding of the mechanisms underlying their polymerase
      acceptance. In addition, the usefulness of chemically altered dNTPs in SELEX and
      related methods of in vitro selection will be highlighted, with a particular
      emphasis on the generation of modified DNA enzymes (DNAzymes) and DNA-based
      aptamers.

PMID- 23154274
TI  - TLRs and IFNs: critical pieces of the autoimmunity puzzle.
AB  - Discoveries revealing the molecular basis of innate immune responses,
      particularly the identification of Toll-like receptors (TLRs) as the major
      recognition sensors for microbial and even self-molecules, have provided new
      insights into the pathogenesis of both systemic and organ-specific autoimmune
      diseases. These insights will permit the development of novel treatment
      modalities for these disorders.

PMID- 23154275
TI  - Autoantibodies, autoimmune disease, and the birth of immune diagnostics.
AB  - The appearance of autoantibody to DNA followed sequentially by the disappearance
      of anti-DNA and appearance of DNA antigen in a patient with systemic lupus
      erythematosus demonstrated that autoantibodies participate in immune complex
      mediated pathogenesis. Continuing studies showed that autoantibodies are also
      useful biomarkers in clinical diagnosis and important reagents for elucidating
      the structure and function of intracellular proteins in cell biology. Recently,
      autoantibodies to tumor-associated antigens have been identified in cancer, and
      these findings have expanded the field of cancer immunodiagnostics.

PMID- 23154276
TI  - Better tools for assessing osteoporosis.
AB  - Some 30 years ago, we applied the newly described method of dual photon
      absorptiometry (DPA) to demonstrate that osteoporotic women with vertebral
      fractures had lost substantially more bone from the vertebrae than controls. This
      opened a whole new field of research into the determinants of bone loss and
      fractures in the axial skeleton and set the stage for subsequent development of
      dual-energy x-ray absorptiometry (DXA) and quantitative computed tomography
      (QCT), which are now the standard methods for assessing osteoporosis severity and
      treatment efficacy.

PMID- 23154277
TI  - Tumors exposed to acute cyclic hypoxia show increased vessel density and delayed
      blood supply.
AB  - The purpose of this study was to investigate the effect of acute cyclic hypoxia
      on tumor vasculature. A-07 human melanoma xenografts growing in dorsal window
      chambers were used as tumor model. Acute cyclic hypoxia was induced by
      periodically exposing tumor-bearing mice to a low oxygen atmosphere. The hypoxia
      treatment consisted of 12 cycles of 10 min of low O(2) (8% O(2) in N(2)) followed
      by 10 min of air for a total of 4 hr. The treatment started the first day after
      tumor initiation, and was given daily for 9 days. Vascular morphology was
      assessed from high-resolution transillumination images, and tumor blood supply
      was assessed from first-pass imaging movies recorded after a bolus of 155 kDa
      tetramethylrhodamine isothiocyanate-labeled dextran had been administered
      intravenously. Hypoxia-treated tumors showed increased vessel density, decreased
      interstitial distance, and delayed blood supply compared to control tumors. The
      increase in vessel density was attributed to an increased number of small
      vessels. In conclusion, acute cyclic hypoxia induced angiogenesis in A-07 tumors
      resulting in increased density of small-diameter vessels and delayed tumor blood
      supply.

PMID- 23154278
TI  - Increasing acclimation period improves the reproducibility of short-heating local
      thermal hyperemia.
AB  - OBJECTIVES: The axon reflex (AR) can be induced by the activation of afferent C
      fibers during local skin heating. The previously used long-heating local thermal
      hyperemia (LTH) protocols tested AR flare by normalizing to endothelial-mediated
      maximal vasodilatation to adjust capillary heterogeneity when the recording sites
      were randomly selected. The AR flare induced by short local heating can be
      reproducible without using the data from subsequent longer heating for
      normalization when the recording sites were fixed with holders in the same
      session. The aim of this study was to investigate the effect of acclimation
      period on the intersession reproducibility of short-heating LTH when the
      recording sites were relocated after a longer interval of 1-3 days. METHODS:
      After 30 or 60 min acclimation, LTH with 5 min heating was assessed on bilateral
      human forearms using single-point laser Doppler flowmetry. The test was repeated
      at the same recording sites again at the same time 1-3 days later. Baseline and
      heating blood flux were analyzed and the data were expressed as different forms.
      Reproducibility of two tests was assessed using coefficient of variation (CV) and
      intra-class correlation coefficient (ICC) statistics. RESULTS: The intersession
      reproducibility of peak cutaneous vascular conductance (CVC) (CV=18.38%,
      ICC=0.82), peak CVC change (CV=20.38%, ICC=0.83) and 4 min area-under-the-curve
      (AUC) (CV=18.66%, ICC=0.75) of the right forearm and time to peak (CV=16.84%,
      ICC=0.52) of the left forearm were acceptable after 30 min acclimation. When the
      acclimation period was increased to 60 min, all of these data except 4 min AUC of
      both sides reached an acceptable level. CONCLUSIONS: The AR flare induced by
      short local heating is reproducible when the recording sites are relocated by a
      predefined rule. The reproducibility of LTH on right forearm is different from
      that on left forearm, and increasing acclimation period improves the
      reproducibility.

PMID- 23154279
TI  - Wall shear stress quantification in the human conjunctival pre-capillary
      arterioles in vivo.
AB  - Blood volume flow (Q), wall shear rate (WSR) and wall shear stress (WSS) were
      quantified, for the first time, in the conjunctival pre-capillary arterioles of
      normal human volunteers with diameters (D) between 6 and 12 MUm. The variation of
      the blood velocity throughout the cardiac cycle was taken into account using high
      speed video microcinematography. The dual effect of arteriolar diameter, firstly
      on the WSR and secondly on the dynamic viscosity of blood, was taken into account
      in the estimation of WSS. The average Q, WSR and WSS, throughout the cardiac
      cycle ranged from 13 to 202 pl/s, 587 to 3515 s(-1) and 1.7 to 21.1 N/m(2)
      respectively. The best fit power law equations, giving the increase of Q and the
      decrease of WSR and WSS with diameter, are presented for the systolic and
      diastolic phase as well as for the averages throughout the cardiac cycle.
      According to the WSS best fit equation, the average WSS decreases from 10.5
      N/m(2) at D=6 MUm down to 2.1 N/m(2) at D=12 MUm.

PMID- 23154280
TI  - In vivo evaluation of venular glycocalyx during hemorrhagic shock in rats using
      intravital microscopy.
AB  - Hemorrhage is responsible for a large percentage of trauma-related deaths but the
      mechanisms underlying tissue ischemia are complex and not well understood.
      Despite the evidence linking glycocalyx degradation and hemorrhagic shock, there
      is no direct data obtained in vivo showing glycocalyx thickness reduction in
      skeletal muscle venules after hemorrhage. We hypothesize that damage to the
      endothelial glycocalyx is a key element in hemorrhage pathophysiology and tested
      the hypothesis that hemorrhage causes glycocalyx degradation in cremaster muscle
      microvessels. We utilized intravital microscopy to estimate glycocalyx thickness
      in 48 microvessels while other microvascular parameters were measured using non
      invasive techniques. Systemic physiological parameters and blood chemistry were
      simultaneously collected. We studied 27 post-capillary venules (<16 MUm diameter)
      of 8 anesthetized rats subjected to hemorrhage (40% of total blood volume). Six
      control rats were equally instrumented but not bled. Dextrans of different
      molecular weights labeled with FITC or Texas Red were injected. Glycocalyx
      thickness was estimated from the widths of the fluorescence columns and from
      anatomical diameter. While control rats did not show remarkable responses, a
      statistically significant decrease of about 59% in glycocalyx thickness was
      measured in venules after hemorrhagic shock. Venular glycocalyx thickness and
      local blood flow changes were correlated: venules with the greatest flow
      reductions showed the largest decreases in glycocalyx. These changes may have a
      significant impact in shock pathophysiology. Intravital microscopy and integrated
      systems such as the one described here may be important tools to identify
      mechanisms by which resuscitation fluids may improve tissue recovery and outcome
      following hemorrhage.

PMID- 23154281
TI  - Difference of foot posture in two cases of exercise-induced foot dystonia.

PMID- 23154282
TI  - The p.G146A and p.P125P polymorphisms in the steroidogenic factor-1 (SF-1) gene
      do not affect the risk for hypospadias in Caucasians.
AB  - Hypospadias is a frequent congenital malformation in boys and is characterized by
      incomplete fusion of the urethral folds. The steroidogenic factor-1 (SF-1, NR5A1)
      gene plays a key role in hypothalamic-pituitary-steroidogenic organ development,
      and has previously been reported to be mutated in individuals with 46,XY disorder
      of sex development. Here, we investigated the role of SF-1 in hypospadias, a
      milder form of 46,XY disorder of sex development. We performed direct sequencing
      analysis of the SF-1 gene in 2 male Caucasian twins exhibiting very severe
      hypospadias, and in 95 Caucasian boys with mild and severe hypospadias. We
      further extended the analysis by investigating 332 mild and severe hypospadias
      cases and 422 male controls using TaqMan assays. Our sequencing revealed a novel
      heterozygous p.R313H (c.938G>A) missense mutation in each twin, and no mutations
      in the 95 Caucasian cases. Instead, a missense p.G146A (c.437G>C), and a silent
      known p.P125P (c.375C>T) polymorphism, respectively, was found in several of the
      latter cases. Further investigation of the 2 polymorphisms in the larger material
      of cases and controls showed no significant genotypic or allelic association. In
      conclusion, the SF-1 gene may not play a significant role in the development of
      hypospadias in Caucasians.

PMID- 23154283
TI  - The role of dendritic cells in Mycobacterium tuberculosis infection.
AB  - The immune response against Mycobacterium tuberculosis is multifactorial,
      involving a network of innate and adaptive immune responses. Characterization of
      the immune response, a clear understanding of the dynamics and interplay of
      different arms of the immune response are critical to allow the development of
      better tools for combating tuberculosis. Dendritic cells (DCs) are one of the key
      cells in bridging innate and adaptive immune response through their significant
      role in capturing, processing and presenting antigens. The outcome of interaction
      of M. tuberculosis with DCs is not fully understood and the available reports are
      contradictory were some findings reported that DCs strengthen the cellular immune
      response against mycobacterium infection whereas others reported M. tuberculosis
      impairs the function of DCs were infected DCs are poor stimulators of M.
      tuberculosis Ag-specific CD4 T cells. Other studies showed that the outcome
      depends on M. tuberculosis strain type and type of receptor on DCs during
      recognition. In this review I shall highlight the recent findings in the outcome
      of interaction of Mycobacterium tuberculosis with DCs.

PMID- 23154285
TI  - The streptococcal hemoprotein receptor: a moonlighting protein or a virulence
      factor?
AB  - The beta-hemolytic group A streptococcus (GAS) is a major pathogen that readily
      uses hemoglobin to satisfy its requirements for iron. The streptococcal
      hemoprotein receptor in GAS plays a central role in heme utilization and binds
      fibronectin and laminin in vitro. Shr inactivation attenuates the virulent M1T1
      GAS strain in two murine infection models and reduces bacterial growth in blood
      and binding to laminin. Shr impact on the globally disseminated M1T1 strain
      underscores the importance of heme uptake in GAS pathogenesis and raises the
      possibility of targeting heme-uptake proteins in the development of new methods
      to combat GAS infections.

PMID- 23154284
TI  - A dendrite in every pie: myeloid dendritic cells in HIV and SIV infection.
AB  - Dendritic cells (DC) are a heterogeneous population of innate immune cells that
      are fundamental to initiating responses against invading pathogens and regulating
      immune responses. Myeloid DC (mDC) act as a bridge between the innate and
      adaptive immune response during virus infections but their role in immunity to
      human immunodeficiency virus (HIV) remains ill-defined. This review examines
      aspects of the mDC response to HIV and its simian counterpart, simian
      immunodeficiency virus (SIV), and emphasizes areas where our knowledge of mDC
      biology and function is incomplete. Defining the potentially beneficial and
      detrimental roles mDC play during pathogenic and stable infection of humans and
      nonhuman primates is crucial to our overall understanding of AIDS pathogenesis.

PMID- 23154286
TI  - Pathology in euthermic bats with white nose syndrome suggests a natural
      manifestation of immune reconstitution inflammatory syndrome.
AB  - White nose syndrome, caused by Geomyces destructans, has killed more than 5
      million cave hibernating bats in eastern North America. During hibernation, the
      lack of inflammatory cell recruitment at the site of fungal infection and erosion
      is consistent with a temperature-induced inhibition of immune cell trafficking.
      This immune suppression allows G. destructans to colonize and erode the skin of
      wings, ears and muzzle of bat hosts unchecked. Yet, paradoxically, within weeks
      of emergence from hibernation an intense neutrophilic inflammatory response to G.
      destructans is generated, causing severe pathology that can contribute to death.
      We hypothesize that the sudden reversal of immune suppression in bats upon the
      return to euthermia leads to a form of immune reconstitution inflammatory
      syndrome (IRIS). IRIS was first described in HIV-infected humans with low helper
      T lymphocyte counts and bacterial or fungal opportunistic infections. IRIS is a
      paradoxical and rapid worsening of symptoms in immune compromised humans upon
      restoration of immunity in the face of an ongoing infectious process. In humans
      with HIV, the restoration of adaptive immunity following suppression of HIV
      replication with anti-retroviral therapy (ART) can trigger severe immune-mediated
      tissue damage that can result in death. We propose that the sudden restoration of
      immune responses in bats infected with G. destructans results in an IRIS-like
      dysregulated immune response that causes the post-emergent pathology.

PMID- 23154287
TI  - Deformed wing virus: the main suspect in unexplained honeybee deaths worldwide.

PMID- 23154288
TI  - Molecular blueprint of uropathogenic Escherichia coli virulence provides clues
      toward the development of anti-virulence therapeutics.

PMID- 23154289
TI  - Turning up Francisella pathogenesis: the LPS thermostat.

PMID- 23154290
TI  - The fate of not sensing phosphate: downregulation of type 1 fimbriae through
      activation of the Pho regulon reduces E. coli urinary tract virulence.

PMID- 23154292
TI  - Remarkable enhancement in ligand-exchange reactivity of thiolate-protected Au25
      nanoclusters by single Pd atom doping.
AB  - The effect of Pd doping on the ligand-exchange reactivity of
      Au(25)(SC(12)H(25))(18) was studied by comparing the ligand-exchange reactivity
      of [Au(25)(SC(12)H(25))(18)](-) and [PdAu(24)(SC(12)H(25))(18)](0) and the
      results clearly demonstrate that, regardless of the kind of incoming thiols and
      solvents, Pd doping greatly increases the rate of ligand exchange of
      Au(25)(SC(12)H(25))(18), indicating an enhanced ease of ligand exchange.

PMID- 23154293
TI  - Characterization of a new animal model of metabolic syndrome: the DahlS.Z
      Lepr(fa)/Lepr(fa) rat.
AB  - OBJECTIVE: The DahlS.Z-Lepr(fa)/Lepr(fa) (DS/obese) rat strain was established
      from a cross between Dahl salt-sensitive rats and Zucker fatty (fa/fa) rats, the
      latter of which harbor a missense mutation in the leptin receptor gene (Lepr). We
      examined whether DS/obese rats might be a suitable animal model of metabolic
      syndrome in humans. METHODS: The systemic pathophysiological and metabolic
      characteristics of DS/obese rats were determined and compared with those of
      homozygous lean littermates, namely, DahlS.Z-Lepr(+)/Lepr(+) (DS/lean) rats.
      RESULTS: Systolic blood pressure was higher in DS/obese rats fed a normal diet
      than in DS/lean rats at 11 weeks of age and thereafter. The survival rate of
      DS/obese rats was significantly lower than that of DS/lean rats at 18 weeks. Body
      weight, visceral and subcutaneous fat mass, as well as heart, kidney and liver
      weights, were increased in DS/obese rats at 18 weeks compared with DS/lean rats.
      Serum low-density lipoprotein (LDL)-cholesterol, triglyceride and insulin
      concentrations, as well as the ratio of LDL-cholesterol to high-density
      lipoprotein-cholesterol levels, were increased in DS/obese rats, whereas serum
      glucose concentration did not differ significantly between DS/obese and DS/lean
      rats. Creatinine clearance was decreased and urinary protein content was
      increased in DS/obese rats, which also manifested lipid accumulation in the liver
      and elevation of serum alanine aminotransferase levels. CONCLUSION: These results
      show that the phenotype of DS/obese rats is similar to that of humans with
      metabolic syndrome, and that these animals may thus be an appropriate model for
      this condition.

PMID- 23154294
TI  - Abdominal adiposity depots are correlates of adverse cardiometabolic risk factors
      in Caucasian and African-American adults.
AB  - OBJECTIVE: Accumulation of adipose tissue is associated with cardiometabolic
      risks. Although visceral adipose tissue (VAT) has been strongly implicated in
      this relationship, there is still some debate regarding the contribution of
      abdominal subcutaneous adipose tissue (SAT). The purpose of this study was to
      determine the contribution of abdominal SAT to cardiometabolic risk factors,
      independent of total and visceral adiposity. These relationships were assessed in
      Caucasian and African Americans. DESIGN: It is a cross-sectional analysis of the
      Pennington Center Longitudinal Study. SUBJECTS: Data were extracted from 1246
      participants. Total body fat mass (FM) was measured by dual-energy X-ray
      absorptiometry, whereas abdominal VAT and SAT areas (cm(2)) were measured with
      computed tomography. The cardiometabolic risk factors included resting blood
      pressure (BP), fasting blood glucose and triglyceride concentrations and high
      density lipoprotein cholesterol (HDL-C). RESULTS: Positive relationships across
      tertiles of VAT were seen for the participants with high glucose, high BP and low
      HDL-C (P<0.043). There was also a significant increase in the percentage of
      participants with two or more cardiometabolic risk factors across most tertiles
      of abdominal SAT (P<0.042). Logistic regression analysis showed that in
      univariate models, all adiposity measures were significantly associated with
      increased odds of having all risk factors in men and women. In multivariate
      models, VAT was significantly associated with most risk factors across gender.
      Abdominal SAT and FM (odds ratios (ORs) 1.3-2.1; all P<0.05) were associated with
      fewer risk factors after accounting for VAT. VAT (OR=5.9 and 5.3) and SAT (OR=2.0
      and 1.8) were both associated with higher odds of the presence of two or more
      cardiometabolic risk factors in both males and females (P<0.001). CONCLUSION: The
      data suggest that abdominal SAT is not protective against unfavorable
      cardiometabolic risk profiles. These conclusions were consistent across ethnic
      groups.

PMID- 23154295
TI  - Short- and long-term glucocorticoid treatment enhances insulin signalling in
      human subcutaneous adipose tissue.
AB  - BACKGROUND: Endogenous or exogenous glucocorticoid (GC) excess (Cushing's
      syndrome) is characterized by increased adiposity and insulin resistance.
      Although GCs cause global insulin resistance in vivo, we have previously shown
      that GCs are able to augment insulin action in human adipose tissue, contrasting
      with their action in skeletal muscle. Cushing's syndrome develops following
      chronic GC exposure and, in addition, is a state of hyperinsulinemia. OBJECTIVES:
      We have therefore compared the impact of short- (24 h) and long-term (7 days) GC
      administration on insulin signalling in differentiated human adipocytes in the
      presence of low or high concentrations of insulin. RESULTS: Both short- (24 h)
      and long-term (7 days) treatment of chub-s7 cells with dexamethasone (Dex) (0.5
      MUM) increased insulin-stimulated pTyr612IRS1 and pSer473akt/PKB, consistent with
      insulin sensitization. Chronic high-dose insulin treatment induced insulin
      resistance in chub-s7 cells. However, treatment with both high-dose insulin and
      Dex in combination still caused insulin sensitization. CONCLUSIONS: In this human
      subcutaneous adipocyte cell line, prolonged GC exposure, even in the presence of
      high insulin concentrations, is able to cause insulin sensitization. We suggest
      that this is an important mechanism driving adipogenesis and contributes to the
      obese phenotype of patients with Cushing's syndrome.

PMID- 23154296
TI  - Effect of trans fatty acid intake on abdominal and liver fat deposition and blood
      lipids: a randomized trial in overweight postmenopausal women.
AB  - BACKGROUND: Intake of industrially produced trans fatty acids (TFAs) is,
      according to observational studies, associated with an increased risk of
      cardiovascular disease, but the causal mechanisms have not been fully elucidated.
      Besides inducing dyslipidemia, TFA intake is suspected to promote abdominal and
      liver fat deposition. OBJECTIVE: We examined the effect of a high intake of TFA
      as part of an isocaloric diet on whole-body, abdominal and hepatic fat
      deposition, and blood lipids in postmenopausal women. METHODS: In a 16-week
      double-blind parallel intervention study, 52 healthy overweight postmenopausal
      women were randomized to receive either partially hydrogenated soybean oil
      providing 15.7 g day(-1) of TFA or a control oil with mainly oleic and palmitic
      acid. Before and after the intervention, body composition was assessed by dual
      energy X-ray absorptiometry, abdominal fat by magnetic resonance (MR) imaging,
      and liver fat by (1)H MR spectroscopy. RESULTS: Compared with the control fat,
      TFA intake decreased plasma high-density lipoprotein (HDL)-cholesterol by 10%,
      increased low-density lipoprotein (LDL)-cholesterol by 18% and resulted in an
      increased LDL/HDL-cholesterol ratio (baseline adjusted mean (95% CI) difference
      between diet groups 0.41 (0.22; 0.60); P<0.001). TFA tended to increase the body
      fat (0.46 (-0.20; 1.17) kg; P=0.16) and waist circumference (1.1 (-0.1; 2.4) cm;
      P=0.08) more than the control fat, whereas neither abdominal nor liver fat
      deposition was affected by TFA. CONCLUSION: The adverse effect of dietary TFA on
      cardiovascular disease risk involves induction of dyslipidemia, and perhaps body
      fat, whereas weight gain-independent accumulation of ectopic fat could not be
      identified as a contributory factor during short-term intake.

PMID- 23154297
TI  - Erythrocyte storage duration is not associated with increased mortality in
      noncardiac surgical patients: a retrospective analysis of 6,994 patients.
AB  - BACKGROUND: More than 5 million patients receive erythrocyte transfusions in the
      United States every year. Previous studies linked the storage duration of
      allogeneic erythrocytes to the risk of severe postoperative complications,
      especially after cardiac or trauma surgery. Limited data are available for
      noncardiac surgical patients. We therefore evaluated the association between
      storage duration of transfused erythrocytes and postoperative all-cause mortality
      among general surgery patients. METHODS: Perioperative data corresponding to
      63,319 adult, general surgery patients were obtained from our registry and merged
      with blood product data. Patients receiving solely leukocyte-reduced, allogeneic
      erythrocyte transfusions were included. Multivariable Cox proportional hazards
      regression was used to characterize the relationship between median erythrocyte
      storage duration and postoperative mortality rate, adjusting for characteristics
      plausibly influencing the storage duration of erythrocytes. RESULTS: Of the 6,994
      patients included in the final analysis, 23, 44, 11, 9, and 13% received 1, 2, 3,
      4, and >=5 erythrocyte units, respectively. The authors found no evidence that
      increasing median storage duration was associated with a difference in the risk
      of postoperative mortality (hazard ratio, 0.99 [0.94-1.04]; P = 0.64). Analyzing
      the mean storage duration of erythrocyte units as a function of year of
      transfusion, the authors demonstrate a relevant decrease in utilization of the
      oldest blood units, whereas young blood storage duration remains nearly
      unchanged. CONCLUSION: The authors' study supports the recent literature in
      surgical and medical patients and underlines the importance of sufficiently
      powered randomized trials to finally resolve the erythrocyte storage duration
      debate.

PMID- 23154298
TI  - Living with a total artificial heart: patients' perspectives.
AB  - BACKGROUND: Advances in mechanical circulatory support have reduced morbidity and
      mortality in end-stage heart failure. To date, there have been no published
      studies examining the psychosocial impact on patients who are supported with a
      total artificial heart (TAH-t). PURPOSE: The purpose of this study was to
      describe the lived experience of patients currently supported by the TAH-t
      awaiting transplant. METHODS: A qualitative method using Giorgi's modification of
      phenomenologic inquiry guided the investigation, which was conducted at a
      transplant center located in the mid-Atlantic region of the United States. A
      purposive sample was selected to reflect participants currently supported by the
      TAH-t. All participants (9 men, 1 woman; mean age, 48.2 years; nonischemic
      etiology, 80%) were in-patients on the progressive care unit at the time of the
      interview and had been supported for at least 30 days. The mean length of device
      therapy was 84.7 days (range, 33-245 days). FINDINGS: Hope for the future was the
      overarching theme. Subthemes included reflections, for better or for worse, the
      secret club, and coping and adaptation. The patients reflected on severity of
      illness, progress, and expressed optimism. For better or for worse described how
      symptoms improved but were offset by restrictions imposed by the technology. The
      secret club described the support provided to help deal with their life
      situation. Coping and adaptation suggested that the patients came to terms with
      and accepted their circumstances. CONCLUSIONS: The findings will help clinicians
      understand patients experiencing a life-changing situation and implications for
      psychosocial interventions.

PMID- 23154300
TI  - Impact of thyrotropin receptor antibody levels on fetal development in two
      successive pregnancies in a woman with Graves' disease.
AB  - BACKGROUND: Treatment with radioiodine for Graves' disease regularly increases
      the level of antithyroid antibodies, and transplacental passage of stimulating
      thyrotropin receptor antibodies (TRAb) may cause fetal hyperthyroidism. CASE
      PRESENTATION: A 21-year-old woman with Graves' disease received radioiodine
      treatment to avoid use of antithyroid drugs in pregnancy. She became pregnant 4
      months later and was euthyroid during pregnancy. In gestational week (GW) 33, she
      was admitted with an increased fetal heart rate of 176-180 beats/min. Fetal
      echocardiography indicated cardiac decompensation. The neonate had severe
      hyperthyroidism (free thyroxine >100 pmol/l, nv 12.0-22.0), cardiac
      insufficiency, insufficient weight gain, goiter and considerably accelerated
      skeletal age. In the mother and neonate, TRAb was >40 IU/l (nv <1.0), indicating
      transplacental passage of stimulating antibodies. After delivery, TRAb remained
      >40 IU/l in the woman, and 18 months later she underwent total thyroidectomy with
      subsequent decline in TRAb. In her next pregnancy, TRAb fluctuated between 38 and
      17 IU/l, and repeated fetal ultrasound showed no goiter or sign of
      hyperthyroidism. In cord blood, TRAb was 10.9 IU/l, and the neonate had normal
      thyroid hormone levels. CONCLUSION: This case report illustrates the impact of
      maternal TRAb level for neonatal outcome in two successive pregnancies.

PMID- 23154299
TI  - Improvements in heart rate recovery among women after cardiac rehabilitation
      completion.
AB  - BACKGROUND: Heart rate recovery (HRR) after exercise cessation is thought to
      reflect the rate of reestablishment of parasympathetic tone. Relatively little
      research has focused on improved HRR in women after completing cardiac
      rehabilitation (CR) exercise training. OBJECTIVE: We examined the influence of
      exercise training on HRR in women completing a traditional CR program and in
      women completing a CR program tailored for women. METHODS: A 2-group randomized
      clinical trial compared HRR between 99 women completing a traditional 12-week CR
      program and 137 women completing a tailored CR program. Immediately upon
      completion of a symptom-limited graded exercise test, HRR was measured at 1
      through 6 minutes. RESULTS: Compared with baseline, improvement in 1-minute HRR
      (HRR1) was similar (P = 0.777) between the tailored (mean [SD], 17.5 [11] to 19.1
      [12]) and the traditional CR program (15.7 [9.0] to 16.9 [9.5]). The amount of
      change in the 2-minute HRR (HRR2) for the tailored (30 [13] to 32.8 [14.6]) and
      traditional programs (28.3 [12.8] to 31.2 [13.7]) also was not different (P =
      0.391). Similar results were observed for HRR at 3 through 6 minutes. Given these
      comparable improvements of the 2 programs, in the full cohort, the factors
      independently predictive of post-CR HRR1, in rank order, were baseline HRR1 (part
      correlation, 0.35; P < 0.001); peak exercise capacity, estimated as metabolic
      equivalents (METs; 0.24, P < 0.001); anxiety (-0.17, P = 0.001); and age (-0.13,
      P = 0.016). The factors independently associated with post-CR HRR2 were baseline
      HRR2 (0.44, P < 0.001), peak METs (0.21, P < 0.001), and insulin use (-0.10, P =
      0.041). CONCLUSIONS: One to 6 minutes after exercise cessation, HRR was
      significantly improved among the women completing both CR programs. The
      modifiable factors positively associated with HRR1 included peak METs and lower
      anxiety, whereas HRR2 was associated with insulin administration and peak METs.
      Additional research on HRR after exercise training in women is warranted.

PMID- 23154301
TI  - Sensory gating, cannabinoids and schizophrenia.
AB  - Sensory gating, a mandatory process in early information processing, has been
      found to be defective in neuropsychiatric diseases such as schizophrenia.
      Understanding the neurobiology of sensory gating may provide insight into
      unravelling the neurobiology of information processing and to yet unanswered
      queries on the pathophysiology of disabling neuropsychiatric diseases. The
      endocannabinoid system has been linked to the pathophysiology of schizophrenia.
      Furthermore, cannabinoids disrupt sensory gating in animals and humans which
      supports the hypothesis that the disruption of sensory gating by alterations in
      the endocannabinoid system is a significant factor in the etiology of
      schizophrenia. Based on the above hypothesis this article reviews the sensory
      gating process in relation to the auditory conditioning-test paradigm with an
      emphasis on its association with the endocannabinoid system and schizophrenia.

PMID- 23154304
TI  - Synthesis of novel indole hydrazone derivatives and evaluation of their
      antiplatelet aggregation activity.
AB  - Based on the existing reports regarding the antiplatelet aggregation activity of
      hydrazone derivatives, a series of indole hydrazone derivatives were considered
      as potential antiplatelet agents and synthesized. The structures of the
      synthesized compounds were confirmed by spectral data and elemental analysis. The
      new indole hydrazone derivatives were evaluated for their ability to inhibit
      platelet aggregation induced by adenosine diphosphate (ADP) and arachidonic acid
      (AA). Compounds 1h and 3h exhibited remarkable activity against arachidonic acid
      induced platelet aggregation with IC(50) values comparable to that of
      indomethacin and compound 1i efficiently inhibited platelet aggregation induced
      by both ADP and AA.

PMID- 23154302
TI  - Combination treatment with progesterone and vitamin D hormone is more effective
      than monotherapy in ischemic stroke: the role of BDNF/TrkB/Erk1/2 signaling in
      neuroprotection.
AB  - We investigated whether combinatorial post-injury treatment with progesterone
      (P4) and vitamin D hormone (VDH) would reduce ischemic injury more effectively
      than P4 alone in an oxygen glucose deprivation (OGD) model in primary cortical
      neurons and in a transient middle cerebral artery occlusion (tMCAO) model in
      rats. In the OGD model, P4 and VDH each showed neuroprotection individually, but
      combination of the "best" doses did not show substantial efficacy; instead, the
      lower dose of VDH in combination with P4 was the most effective. In the tMCAO
      model, P4 and VDH were given alone or in combination at different times post
      occlusion for 7 days. In vivo data confirmed the in vitro findings and showed
      better infarct reduction at day 7 and functional outcomes (at 3, 5 and 7 days
      post-occlusion) after combinatorial treatment than when either agent was given
      alone. VDH, but not P4, upregulated heme oxygenase-1, suggesting a pathway for
      the neuroprotective effects of VDH differing from that of P4. The combination of
      P4 and VDH activated brain-derived neurotrophic factor and its specific receptor,
      tyrosine kinase receptor-B. Under specific conditions VDH potentiates P4's
      neuroprotective efficacy and should be considered as a potential partner of P4 in
      a low-cost, safe and effective combinatorial treatment for stroke.

PMID- 23154305
TI  - Is it safe to proceed with thrombolytic therapy for acute ischemic stroke in a
      patient with cardiac myxoma?.

PMID- 23154306
TI  - Sexing frogs by real-time PCR: using aromatase (cyp19) as an early ovarian
      differentiation marker.
AB  - Most anurans have no identified sex-markers; therefore, alternative methods for
      identification of early changes in sex ratios are required. In this study,
      Lithobates sylvaticus and Silurana tropicalis tadpoles were sampled at different
      developmental stages covering the entire process of sex differentiation. Three
      candidate genes known to be involved in sex differentiation in other vertebrate
      species were selected to develop a method to identify phenotypic sex in frogs:
      cytochrome p450 aromatase (cyp19), forkhead box L2 (foxl2) and the cytochrome 17
      alpha-hydroxylase/17,20 lyase (cyp17). Cloning of these genes revealed nucleotide
      identity values ranging between 75-97% when compared to other amphibian species.
      Gene expression of cyp17,cyp19 and foxl2 in L. sylvaticus adult gonads and gonad
      mesonephros complex (GMC) of tadpoles was analyzed by real-time RT-PCR. Results
      showed clear sexually dimorphic patterns in the expression of the 3 genes. Our
      analysis reveals that GMC gene expression levels of cyp19 alone can be used as a
      robust predictor of phenotypic sex in L. sylvaticus tadpoles. In addition, we
      validated this method measuring cyp19 mRNA levels in S. tropicalis GMCs. We
      propose measuring cyp19 as a tool to study the effects of chemical contaminants
      (including endocrine disrupting compounds) on amphibian gonadal development and
      sex ratios in the future.

PMID- 23154307
TI  - Perinatal periodontal disease reduces social behavior in male offspring.
AB  - OBJECTIVE: Our objective was to verify whether prenatal maternal periodontitis is
      a risk factor for the development of central nervous system disorders in rats.
      METHODS: Periodontitis was induced by placing a ligature around the upper and
      lower first molars in 9 female Wistar rats (experimental group); 9 rats were left
      unligated (control group). The maternal general activity in an open field was
      observed on gestational day (GD) 0, GD 4, and GD 14, and the maternal performance
      was assessed on the second day after birth. The pups' play behavior was assessed
      on postnatal day 30. The relative level of reelin was measured in the frontal
      cortex by real-time PCR analysis. RESULTS: The results showed that, compared with
      the control group, (1) the general activity in female rats with periodontitis was
      decreased, (2) the maternal performance of these rats was not modified by
      periodontitis, (3) the play behavior of pups from dams with periodontitis was
      decreased, and (4) there were no differences in the frontal cortex reelin levels
      of pups from dams with periodontitis. CONCLUSIONS: We conclude that pre- and
      postnatal periodontitis induces maternal sickness behavior and reduces the pups'
      play behavior without interference with frontal cortex reelin expression.

PMID- 23154308
TI  - Bismuth nanowires with very low lattice thermal conductivity as revealed by the
      3omega method.
AB  - Thermoelectric materials transform temperature gradients to voltages and vise
      versa. Despite their many advantages, devices based on thermoelectric materials
      are used today only in a few applications, due to their low efficiency, which is
      described by the figure of merit ZT. Theoretical studies predict that scaling
      down these materials to the nanometric scale should enhance their efficiency
      partially due to a decrease in their lattice thermal conductivity. In this work
      we determine for the first time the lattice thermal conductivity of 40 nm bismuth
      (Bi) nanowires (NWs), i.e. NWs with a diameter comparable to the Fermi wavelength
      of charge carriers in this material. We find a surprisingly low lattice thermal
      conductivity of 0.13 +/- 0.05 W K(-1) m(-1) at 77 K. A quantitative argument,
      which takes into account several unique properties of Bi, is given to explain
      this unusual finding.

PMID- 23154309
TI  - Nanomotor-based biocatalytic patterning of helical metal microstructures.
AB  - A new nanomotor-based surface-patterning technique based on the movement of a
      magnetically powered enzyme-functionalized flexible nanowire swimmer offers the
      ability to create complex helical metal microstructures.

PMID- 23154310
TI  - Eye on the prize.

PMID- 23154311
TI  - SIDATRAT: informatics to improve HIV/AIDS care.
AB  - AIDS is a major cause of death in the Caribbean, a region with a high prevalence
      of HIV. However, prevalence in Cuba's population aged 15 to 49 years, despite a
      slight increase in recent years, is considered extremely low (0.1%). At the close
      of 2010, 5692 Cuban patients were receiving antiretroviral therapy. SIDATRAT, an
      informatics system, was developed at the Pedro Kouri Tropical Medicine Institute
      in Havana to ensure proper monitoring and followup of drug administration.
      Functioning on a web platform utilizing an Apache server, PHP and MySQL, it
      records patients' general information, CD4 counts, viral load and data from other
      laboratory tests, as well as endoscopic and imaging studies. It also compiles
      information on their AIDS classification, opportunistic infections, HIV subtype
      and resistance studies, followup consultations, drug regimen, adverse reactions
      to medications, changes in drug combinations, and survival; and tracks total
      number of individuals under treatment. SIDATRAT follows the client-server
      philosophy and enables access by authorized users throughout Cuba via the health
      informatics network. SIDATRAT has been found effective in supporting quality care
      for persons living with HIV/AIDS and universal access to antiretroviral therapy,
      compiling most of the information needed for decisionmaking on patient health and
      therapies. SIDATRAT has been offered to the UNDP office in Havana for sharing
      with other developing countries that may wish to adapt or implement it.

PMID- 23154312
TI  - PAHO's presence in Cuban health: Jose Luis Di Fabio PhD. PAHO/WHO representative
      in Cuba. Interview by Gail Reed.

PMID- 23154313
TI  - Reducing case fatality from acute myocardial infarction in Cienfuegos, Cuba, 1994
      2009.
AB  - Between 1994 and 2009, the Dr Gustavo Aldereguia University Hospital of
      Cienfuegos, Cuba implemented a series of interventions that reduced acute
      myocardial infarction case fatality rate from 47% to 15%. These interventions
      were part of an institutional plan for myocardial infarction included in the
      hospital's overall quality assurance strategy. Outcomes resulted primarily from
      organizational changes (from upgrading of the hospital emergency department and
      provincial emergency system to creation of a comprehensive coronary care unit and
      a chest pain center); optimizing use of effective drugs (streptokinase, aspirin,
      ACE inhibitors and beta blockers); adherence to clinical practice guidelines; and
      continual and participatory evaluation and adjustment.

PMID- 23154314
TI  - Acute myocardial infarction mortality in Cuba, 1999-2008.
AB  - INTRODUCTION: Acute myocardial infarction is one of the leading causes of death
      in the world. This is also true in Cuba, where no national-level epidemiologic
      studies of related mortality have been published in recent years. OBJECTIVE:
      Describe acute myocardial infarction mortality in Cuba from 1999 through 2008.
      METHODS: A descriptive study was conducted of persons aged >=25 years with a
      diagnosis of acute myocardial infarction from 1999 through 2008. Data were
      obtained from the Ministry of Public Health's National Statistics Division
      database for variables: age; sex; site (out of hospital, in hospital or in
      hospital emergency room) and location (jurisdiction) of death. Proportions, age-
      and sex-specific rates and age-standardized overall rates per 100,000 population
      were calculated and compared over time, using the two five-year time frames
      within the study period. RESULTS: A total of 145,808 persons who had suffered
      acute myocardial infarction were recorded, 75,512 of whom died, for a case
      fatality rate of 51.8% (55.1% in 1999-2003 and 49.7% in 2004-2008). In the first
      five-year period, mortality was 98.9 per 100,000 population, falling to 81.8 per
      100,000 in the second; most affected were people aged >=75 years and men. Of
      Cuba's 14 provinces and special municipality, Havana, Havana City and Camaguey
      provinces, and the Isle of Youth Special Municipality showed the highest
      mortality; Holguin, Ciego de Avila and Granma provinces the lowest. Out-of
      hospital deaths accounted for the greatest proportion of deaths in both five-year
      periods (54.8% and 59.2% in 1999-2003 and 2004-2008, respectively). CONCLUSIONS:
      Although risk of death from acute myocardial infarction decreased through the
      study period, it remains a major health problem in Cuba. A national acute
      myocardial infarction case registry is needed. Also required is further research
      to help elucidate possible causes of Cuba's high acute myocardial infarction
      mortality: cardiovascular risk studies, studies of out-of-hospital mortality and
      quality of care assessments for these patients.

PMID- 23154315
TI  - Audio computer-assisted self interview compared to traditional interview in an
      HIV-related behavioral survey in Vietnam.
AB  - INTRODUCTION: Globally, population surveys on HIV/AIDS and other sensitive topics
      have been using audio computer-assisted self interview for many years. This
      interview technique, however, is still new to Vietnam and little is known about
      its application and impact in general population surveys. One plausible
      hypothesis is that residents of Vietnam interviewed using this technique may
      provide a higher response rate and be more willing to reveal their true behaviors
      than if interviewed with traditional methods. OBJECTIVE: This study aims to
      compare audio computer-assisted self interview with traditional face-to-face
      personal interview and self-administered interview with regard to rates of
      refusal and affirmative responses to questions on sensitive topics related to
      HIV/AIDS. METHODS: In June 2010, a randomized study was conducted in three cities
      (Ha Noi, Da Nan and Can Tho), using a sample of 4049 residents aged 15 to 49
      years. Respondents were randomly assigned to one of three interviewing methods:
      audio computer-assisted self interview, personal face-to-face interview, and self
      administered paper interview. Instead of providing answers directly to
      interviewer questions as with traditional methods, audio computer-assisted self
      interview respondents read the questions displayed on a laptop screen, while
      listening to the questions through audio headphones, then entered responses using
      a laptop keyboard. A MySQL database was used for data management and SPSS
      statistical package version 18 used for data analysis with bivariate and
      multivariate statistical techniques. Rates of high risk behaviors and mean values
      of continuous variables were compared for the three data collection methods.
      RESULTS: Audio computer-assisted self interview showed advantages over comparison
      techniques, achieving lower refusal rates and reporting higher prevalence of some
      sensitive and risk behaviors (perhaps indication of more truthful answers).
      Premarital sex was reported by 20.4% in the audio computer-assisted self
      interview survey group, versus 11.4% in the face-to-face group and 11.1% in the
      self-administered paper questionnaire group. The pattern was consistent for both
      male and female respondents and in both urban and rural settings. Men in the
      audio computer-assisted self-interview group also reported higher levels of high
      risk sexual behavior--such as sex with sex workers and a higher average number of
      sexual partners--than did women in the same group. Importantly, item refusal
      rates on sensitive topics tended to be lower with audio computer-assisted self
      interview than with the other two methods. CONCLUSIONS: Combined with existing
      data from other countries and previous studies in Vietnam, these findings suggest
      that researchers should consider using audio computer-assisted self interview for
      future studies of sensitive and stigmatized topics, especially for men.

PMID- 23154316
TI  - Clinical impact of RehaCom software for cognitive rehabilitation of patients with
      acquired brain injury.
AB  - We describe the clinical impact of the RehaCom computerized cognitive training
      program instituted in the International Neurological Restoration Center for
      rehabilitation of brain injury patients. Fifty patients admitted from 2008
      through 2010 were trained over 60 sessions. Attention and memory functions were
      assessed with a pre- and post-treatment design, using the Mini-Mental State
      Examination, Wechsler Memory Scale and Trail Making Test (Parts A and B).
      Negative effects were assessed, including mental fatigue, headache and eye
      irritation. The program's clinical usefulness was confirmed, with 100% of
      patients showing improved performance in trained functions.

PMID- 23154317
TI  - An efficient sampling approach to surveillance of non-communicable disease risk
      factors in Cienfuegos, Cuba.
AB  - One of the most common shortcomings in non-communicable disease risk factor
      surveillance, especially in prevalence studies, is sampling procedures, which can
      and do compromise accuracy and reliability of derived estimates. Moreover,
      sampling consumes significant time and resources. Since the early 1990s, risk
      factor surveys in Cienfuegos province, Cuba have paid particular attention to
      careful sampling methods. The new survey conducted in 2011 was not only
      statistically rigorous but introduced an innovative, more efficient method. This
      article provides a detailed description of the sample design employed to optimize
      resource use without compromising selection rigor.

PMID- 23154318
TI  - New indicators proposed to assess tuberculosis control and elimination in Cuba.
AB  - Following 48 years of successful operation of the National Tuberculosis Control
      Program, Cuban health authorities have placed tuberculosis elimination on the
      agenda. To this end some tuberculosis control processes and their indicators need
      redesigned and new ones introduced, related to: number and proportion of
      suspected tuberculosis cases among vulnerable population groups; tuberculosis
      suspects with sputum microscopy and culture results useful for diagnosis
      (interpretable); and number of identified contacts of reported tuberculosis cases
      who were fully investigated. Such new indicators have been validated and
      successfully implemented in all provinces (2011-12) and are in the approval
      pipeline for generalized use in the National Tuberculosis Control Program. These
      indicators complement existing criteria for quality of case detection and support
      more comprehensive program performance assessment.

PMID- 23154319
TI  - Community engagement, personal responsibility and self help in Cuba's health
      system reform.
AB  - In 2011 the Cuban health system began a process of sectoral reform to maintain
      and improve the health of Cuba's population, in response to new challenges and
      demands in the health sector and population health status. The main actions
      involved are reorganization, consolidation and regionalization of services and
      resources. Although community engagement and personal responsibility are not
      explicitly mentioned in the strategy document, it is advisable to use this
      opportunity to revitalize both topics and encourage appropriate and full
      incorporation into the Cuban health system. Both are consistent with the
      objectives and actions of system reforms proposed, in that they allow the various
      social actors to assume shared responsibility in working toward social goals--in
      this case, health gains. This approach also recognizes that reaching such goals
      is a collective endeavor, to be pursued according to ethical principles
      (beneficence as responsibility and justice as solidarity), with community
      involvement and personal responsibility emerging as two important factors subject
      to reorientation in the context of the health system reform under way.

PMID- 23154320
TI  - Banishing biases to save lives: introducing genetic testing for familial cancers.

PMID- 23154321
TI  - Impaired hypothalamic Fto expression in response to fasting and glucose in obese
      mice.
AB  - OBJECTIVE: Recent genome-wide association studies have identified a strong
      association between obesity and common variants in the fat mass and obesity
      associated (FTO) gene. FTO has been detected in the hypothalamus, but little is
      known about its regulation in that particular brain structure. The present study
      addressed the hypothesis that hypothalamic FTO expression is regulated by
      nutrients, specifically by glucose, and that its regulation by nutrients is
      impaired in obesity. RESEARCH DESIGN AND METHODS: The effect of intraperitoneal
      (i.p.) or intracerebroventricular (i.c.v.) administration of glucose on
      hypothalamic Fto mRNA levels was examined in fasted mice. Additionally, the
      effect of glucose on Fto mRNA levels was also investigated ex vivo using mouse
      hypothalamic explants. Lastly, the effect of i.p. glucose injection on
      hypothalamic Fto immunoreactivity and food intake was compared between lean wild
      type and obese ob/ob mice. RESULTS: In wild-type mice, fasting reduced both Fto
      mRNA levels and the number of Fto-immunoreactive cells in the hypothalamus,
      whereas i.p. glucose treatment reversed this effect of fasting. Furthermore,
      i.c.v. glucose treatment also increased hypothalamic Fto mRNA levels in fasted
      mice. Incubation of hypothalamic explants at high glucose concentration increased
      Fto mRNA levels. In ob/ob mice, both fasting and i.p. glucose treatment failed to
      alter the number of Fto-immunoreactive cells in the hypothalamus. Glucose-induced
      feeding suppression was abolished in ob/ob mice. CONCLUSION: Reduction in
      hypothalamic Fto expression after fasting likely arises at least partly from
      reduced circulating glucose levels and/or reduced central action of glucose.
      Obesity is associated with impairments in glucose-mediated regulation of
      hypothalamic Fto expression and anorexia. Hypothalamic Fto-expressing neurons may
      have a role in the regulation of metabolism by monitoring metabolic states of the
      body.

PMID- 23154322
TI  - Primary antiphospholipid syndrome in monozygotic twins.
AB  - Monozygotic twins, 27 years old, with primary anti-phospholipid syndrome have
      been described. The first of the twins had obstetric morbidities (one miscarriage
      at 12 weeks and premature birth of a growth-restricted fetus at 27 weeks
      secondary to pre-eclampsia) and the second had venous thrombosis. Lupus
      anticoagulant was present in both and anti-cardiolipin antibodies were present in
      high titres when re-tested at appropriate intervals. Development of clinical
      features of APS in monozygotic twins points to an underlying genetic basis in the
      pathogenesis of anti-phospholipid syndrome.

PMID- 23154323
TI  - Impact of formulary restriction with prior authorization by an antimicrobial
      stewardship program.
AB  - In an era of increasing antimicrobial resistance and few antimicrobials in the
      developmental pipeline, many institutions have developed antimicrobial
      stewardship programs (ASPs) to help implement evidence-based (EB) strategies for
      ensuring appropriate utilization of these agents. EB strategies for accomplishing
      this include formulary restriction with prior authorization. Potential
      limitations to this particular strategy include delays in therapy, prescriber
      pushback, and unintended increases in use of un-restricted antimicrobials;
      however, our ASP found that implementing prior authorization for select
      antimicrobials along with making a significant effort to educate clinicians on
      criteria for use ensured more appropriate prescribing of these agents, hopefully
      helping to preserve their utility for years to come.

PMID- 23154324
TI  - Removing atmospheric turbulence via space-invariant deconvolution.
AB  - To correct geometric distortion and reduce space and time-varying blur, a new
      approach is proposed in this paper capable of restoring a single high-quality
      image from a given image sequence distorted by atmospheric turbulence. This
      approach reduces the space and time-varying deblurring problem to a shift
      invariant one. It first registers each frame to suppress geometric deformation
      through B-spline-based nonrigid registration. Next, a temporal regression process
      is carried out to produce an image from the registered frames, which can be
      viewed as being convolved with a space invariant near-diffraction-limited blur.
      Finally, a blind deconvolution algorithm is implemented to deblur the fused
      image, generating a final output. Experiments using real data illustrate that
      this approach can effectively alleviate blur and distortions, recover details of
      the scene, and significantly improve visual quality.

PMID- 23154325
TI  - Detecting motion through dynamic refraction.
AB  - Refraction causes random dynamic distortions in atmospheric turbulence and in
      views across a water interface. The latter scenario is experienced by submerged
      animals seeking to detect prey or avoid predators, which may be airborne or on
      land. Man encounters this when surveying a scene by a submarine or divers while
      wishing to avoid the use of an attention-drawing periscope. The problem of
      inverting random refracted dynamic distortions is difficult, particularly when
      some of the objects in the field of view (FOV) are moving. On the other hand, in
      many cases, just those moving objects are of interest, as they reveal animal,
      human, or machine activity. Furthermore, detecting and tracking these objects
      does not necessitate handling the difficult task of complete recovery of the
      scene. We show that moving objects can be detected very simply, with low false
      positive rates, even when the distortions are very strong and dominate the object
      motion. Moreover, the moving object can be detected even if it has zero mean
      motion. While the object and distortion motions are random and unknown, they are
      mutually independent. This is expressed by a simple motion feature which enables
      discrimination of moving object points versus the background.

PMID- 23154326
TI  - Annals of plastic surgery issue of the Taiwan Society of Plastic Surgery.

PMID- 23154327
TI  - The love surrounding the first skin graft in Taiwan: "British skin" that will
      stay in Taiwanese hearts.
AB  - There is a painting that looks like a representation of a simple surgical
      procedure. However, it holds a warm story of the love surrounding the first skin
      graft made by Dr. David Landsborough III for a Taiwanese child in 1928. He
      harvested the donor skin from his wife, Marjorie Landsborough, to save a poor
      boy. Although the grafted skin could not grow onto the wound, the graft of love
      was permanently imprinted on Taiwanese People's hearts. The first Taiwanese
      recipient of MD, PhD degree, Dr. Tsung-Ming Tu invited an artist to recreate and
      draw the surgical procedure to immortalize the unforgettable love and memory of
      Dr. Landsborough III. The painting hanging on the hospital wall portrays an
      important professional role model for every student and health care provider. The
      life story of this medical missionary in Formosa from 1895 to 1936 contributed
      greatly to the development of medical care in Taiwan. It is hoped that this
      story, outlining great love and selflessness, can be glorified and remembered for
      the world to appreciate for generations to come.

PMID- 23154328
TI  - Trismus release in oral cancer patients.
AB  - Trismus is a common problem among oral cancer patients. This report aimed to
      study the inciting factors of trismus and to find out the rationale of trismus
      release. Between 1996 and 2008, 61 oral cancer patients with retrievable records
      of interincisor distance (IID) were analyzed by retrospective chart review. The
      IID decreased from 31.4 (12.4) to 24.9 (12.0) mm in 36 patients undergoing cancer
      ablation only (P = 0.001). Other variables prompting trismus include buccal
      cancer (P = 0.017), radiotherapy (P = 0.008), and recurrence (P = 0.001). In
      contrast, the IID improved from 11.7 (7.1) to 22.7 (11.9) mm in 25 patients
      receiving cancer ablative and trismus releasing surgeries (P = 0.000). The
      improvement fared better in individuals with IID less than 15 mm than the others
      (P = 0.037). In conclusion, involvement of buccal region, ablative surgery,
      radiotherapy, and recurrence are provocative factors of trismus. Patients with
      IID less than 15 mm will benefit from releasing surgery significantly. Others may
      better be handled with conservative managements firstly, and enrolled as
      candidates of surgical release only until the patients entertained a 28-month
      period of disease-free interval, by which time the risk of recurrence would be
      markedly reduced.

PMID- 23154329
TI  - The treatment of bone exposure in burns by using artificial dermis.
AB  - BACKGROUND: The treatment of bone-exposed wounds with artificial dermis is not
      widely accepted in burn patients because of uncertain clinical results. This
      article aimed to review our clinical experience with this technique. METHODS: We
      implanted artificial dermis in 11 bone-exposed burns. Implantation was directly
      performed on bones with periosteum, whereas bones without periosteum were
      trephinated or burred before implantation. All wounds were closed by secondary
      skin grafting. RESULTS: The mean patient age was 49 years. Lower extremity is the
      most common site of bone exposure. The mean bone exposed area was 55.6 cm,
      whereas the mean Integra-implanted area was 86.7 cm. The overall implant take
      rate was 91%, and the skin grafting success rate was 80%. No secondary breakdown
      was noted after a 2-year follow-up. CONCLUSIONS: This study confirms that
      artificial dermis can be an alternative treatment tool for burns with exposed
      bones, especially in patients with limited donor sites.

PMID- 23154330
TI  - Reconstruction of advance head and neck cancer patients after tumor ablation with
      simultaneous multiple free flaps: indications and prognosis.
AB  - Simultaneous multiple free flaps have become a useful option in head and neck
      reconstructions. We performed a 10-year retrospective study between 2001 and
      2010. There were 58 men and 1 woman. The overall mortality rate was 51.7%. The
      longest surviving patient is 9 years and 4 months, whereas the shortest surviving
      patient was 72 days. The mean survival period was 47.1 (6.8) months. Age (P =
      0.755) and tumor size (P = 0.115) did not play a major role, but surgical margin,
      lymph node, and tumor recurrence were significant in patient survival with a P
      value of 0.026, 0.01, and 0.026, respectively. If wide excision with a margin
      that can be free of tumor can be performed, lymph nodes are not involved, and
      this is a primary tumor, then time and effort should be spent in a successful
      simultaneous multiple free flap reconstruction.

PMID- 23154331
TI  - The concept of "two arches" in mandibular reconstruction.
AB  - To optimize the outcome of the free fibula flap in mandibular reconstruction, the
      central portion of the mandible can be divided into upper and lower arches during
      preoperative evaluation and planning. We present 2 cases requiring mandibular
      reconstruction with free fibula flap after ameloblastoma excision, to illustrate
      the "two arches" concept and its applicability in mandibular reconstruction. The
      postoperative course was uneventful. Follow-up at 24 months postoperative
      revealed a considerable restoration in facial appearance and provided functional
      teeth. Recent advances in mandibular reconstruction could be further refined
      through the application of the "two arches" concept. This approach simplifies
      surgical planning in selective cases and directs the attention of surgeons to the
      specific needs of the 2 distinct regions of the mandible during reconstruction.

PMID- 23154332
TI  - Modified tenodesis method for treatment of mallet fractures.
AB  - INTRODUCTION: Mallet fractures are avulsions of the terminal extensor tendon from
      the base of the distal phalangeal bone with a bony fragment. Surgical treatment,
      which provides accurate anatomical reduction and rigid fixation, is recommended
      for mallet fractures with involvement of more than one third of the base of the
      distal phalangeal bone. Various surgical methods have been reported, but there is
      still no standard treatment modality. The purpose of this investigation was to
      assess the results of our modified tenodesis method for mallet fractures.
      MATERIALS AND METHODS: Using our method, the dorsal fracture fragment was reduced
      and fixed to the main part of the distal phalangeal bone by 2 stitches of "figure
      of-eight" 4-0 Prolene sutures. We reviewed 12 consecutive patients with 13 mallet
      fractures treated with our modified tenodesis method between January 2009 and
      March 2012. This retrospective study was composed of 7 male and 5 female
      patients, with a mean age of 35.7 years (range, 25-56 years). All patients
      underwent surgical treatment and sequent 3-week finger splinting. Patient follow
      up lasted 3 to 6 months, with a mean period of 5.2 months. RESULTS: The modified
      tenodesis method allowed accurate anatomical reconstruction of the injured
      extensor mechanism. Grading by Crawford criteria showed that the outcome was
      "excellent" in 8 of 13 digits and "good" in 5 of 13 digits. The follow-up hand x
      rays also revealed congruent joint surfaces of distal interphalangeal joints with
      no evidence of joint space narrowing. No wound complications were encountered,
      and all the patients returned to normal activities without any disability.
      CONCLUSIONS: The modified tenodesis method is simple and effective to provide
      accurate anatomical reduction and fixation for treatment of type I mallet
      fractures. No device penetration of the small bony fragment or pinning through
      the distal interphalangeal joint is required, and the surgical complication rate
      is low. We recommend this treatment modality for all but chronic cases.

PMID- 23154333
TI  - Successful treatment of Kasabach-Merritt phenomenon with intralesional
      corticosteroid injections: a case series.
AB  - Kasabach-Merritt phenomenon (KMP) is a rare and life-threatening disease of
      vascular tumor combined with severe consumptive coagulopathy. Currently, there is
      no established effective treatment of KMP. In this case series, from 2006 to
      2008, we treated 6 pediatric patients with newly diagnosed KMP using
      intralesional corticosteroid injections. The severity and progression of the
      disease were closely monitored with clinical photographs, blood sampling, and
      tissue biopsies. The 6 pediatric patients (5 females and 1 male) showed tumor
      regression after treatments. All coagulopathies were corrected. The average
      duration of treatment was 3.8 months. Complete tumor regression was observed at
      approximately 3 years. Treatment was complicated in 1 patient with transient
      growth retardation. Treatment based on intralesional corticosteroid injections is
      effective for pediatric patients with KMP. Treatment-associated complications
      seemed to be reversible and acceptable by severity level.

PMID- 23154334
TI  - The significance of close but negative excision margin for treatment of soft
      tissue sarcoma.
AB  - Wide excision is the major recommendation for management of soft-tissue sarcomas.
      Pathologic reports of postexcision sarcomas revealed very close (within 2 mm) but
      clear excision margins. This investigation was a retrospective study to determine
      whether wide reexcision plus radiotherapy (R/T), or R/T only, yielded better
      outcomes. MATERIALS AND METHODS: We evaluated our soft-tissue sarcoma cases who
      had received wide excision in the past 15 years. The surgical margin conditions
      (negative, positive, or close margins) and pathologic status were evaluated. The
      different management modalities for each condition were also evaluated
      individually and discussed. RESULTS: There were 73 cases from 1995 to 2010 in our
      section who had received wide excision. The overall recurrence rate was 24.6%. In
      cases with margin positive, the recurrence rate was 20% (2/8) after quick
      reexcision. However, the recurrence rate was 56% in patients who received R/T but
      without quick reexcision. In cases with close resection margins (<2 mm) with no
      reexcision but R/T, the recurrence rate was 45%, and all of them had a high-grade
      malignancy sarcoma. The other nonrecurrence cases (55%) had low-grade malignancy
      or well-differentiated sarcoma.In summary, in cases with positive margin sarcoma,
      quick reexcision plus R/T was suggested and the recurrence rate was relatively
      low. In soft-tissue sarcoma cases with close margin, we believe quick reexcision
      plus R/T is necessary, especial in high-grade, poor differentiated soft-tissue
      sarcomas.

PMID- 23154335
TI  - Are auricular keloids and persistent hypertrophic scars resectable? The role of
      intrascar excision.
AB  - BACKGROUND: Intrascar excision with debulking procedure is a good choice for scar
      revision in unique 3-dimensional facial aesthetic units, especially in the
      auricular area. It can remove or reduce scars in a shorter course without
      distortion of the surrounding anatomic structures and visible operative scars.
      This retrospective study was done to present intrascar excision procedures in
      persistent auricular hypertrophic scars or keloids. METHODS: Between 1997 and
      2010, 18 ears in 13 patient cases with persistent hypertrophic scars and/or
      keloids in their external ear due to burns or trauma were collected for
      evaluation. There were 10 males and 3 females. The age distributions ranged from
      5 to 49 years with an average of 20.1 years. All received intrascar excision with
      debulking procedure for their ear deformity. One case combined with YV-plasty
      procedure to obtain better aesthetic result. The follow-up period ranged from 0.3
      to 14 years with an average of 3.6 years. RESULTS: There was no recurrence in a
      series of average 3.6 years follow-up. Of the 13 patients, 11 (84.6%) objectively
      presented good and satisfactory surgical outcomes and the other 2 patients were
      acceptable. CONCLUSIONS: The intrascar excision in auricular persistent scars or
      keloids has the following advantages: it (1) achieves primary closure, (2) does
      not distort the anatomic landmarks, (3) does not sacrifice the important
      structures, (4) has a debulking effect, (5) can be done anytime, even if scars
      are not mature, (6) has good cosmetic results, (7) may combine with Z- or VY
      plasty for functional improvement, and (8) has minimal complications.

PMID- 23154336
TI  - Expanding the applications of the pedicled anterolateral thigh and vastus
      lateralis myocutaneous flaps.
AB  - We describe our experience in expanding the use of pedicled anterolateral thigh
      and vastus lateralis myocutaneous flaps. A total of 33 patients underwent 34
      flaps between March 2003 and January 2012. The defects included 18 ischial, 3
      trochanteric, 5 lower abdomen, 2 perineogenital, 1 groin, and 5 knee defects.
      There were 29 proximal pedicled (2 of which were preexpanded), 3 distal pedicled,
      and 2 propeller flaps. Complications included 1 total necrosis, 1 partial
      necrosis, 3 wound dehiscence in recipient site, 1 hematoma, and 1 donor-site
      dehiscence. The total flap survival rate was 94%. There were no donor-site
      morbidities except poor cosmesis in the skin-grafted sites. Pedicled
      anterolateral thigh flap is highly versatile with a wide arc of rotation. A
      proximal pedicled flap can be used for lower abdomen, perineogenital, ischial,
      and trochanteric defects and the distal pedicled or a propeller flap for knee and
      proximal lower leg defects.

PMID- 23154337
TI  - The effect of hyperbaric oxygen and air on cartilage tissue engineering.
AB  - There is an urgent need to develop tissue-engineered cartilage for patients
      experiencing joint malfunction due to insufficient self-repairing capacity of
      articular cartilage. The aim of this research was to explore the effect of
      hyperbaric oxygen and air on tissue-engineered cartilage formation from human
      adipose-derived stem cells seeding on the gelatin/polycaprolactone biocomposites.
      The results of histological analyses indicate that under hyperbaric oxygen and
      air stimulation, the cell number of chondrocytes in cartilage matrix was not
      significantly increased, but the 1,9-dimethylmethylene blue assay showed that the
      glycosaminoglycans syntheses markedly increased compared to the control group. In
      quantification real-time polymerase chain reaction results, the chondrogenic
      specific gene expression of SOX9, aggrecan, and COL2A1 were compared
      respectively. Within the limitation of this study, it was concluded that 2.5
      atmosphere absolute oxygen and air may provide a stress environment to help
      cartilage tissue engineering development.

PMID- 23154338
TI  - Adipose-derived stem cells seeded on acellular dermal matrix grafts enhance wound
      healing in a murine model of a full-thickness defect.
AB  - INTRODUCTION: The promotion of wound healing using dermal substitutes has become
      increasingly widespread, but the outcomes of substitute-assisted healing remain
      functionally deficient. Adipose-derived stem cells (ASCs) have been investigated
      widely in regenerative medicine and tissue engineering, and they have the
      potential to enhance wound healing. In this study, we focused on investigating
      the effects and mechanism of ASCs combined with an acellular dermal matrix (ADM)
      to treat full-thickness cutaneous wounds in a murine model. METHODS: The ADM was
      prepared from the dorsal skin of nude mice by decellularization by treatment with
      trypsin followed by Triton X-100. The human ASCs were isolated and cultured from
      abdominal lipoaspirate. We created a rounded, 8-mm, full-thickness cutaneous
      wound in nude mice and divided the mice into the following 4 groups: silicon
      sheet cover only, silicon sheet with spreading ASCs, ADM only, and ASCs seeded on
      ADM. The granulation thickness was evaluated by histology after 7 days. Further
      comparisons between the ADM only and ASC-seeded ADM groups were undertaken by
      assessing the reepithelialization ratio and blood vessel density at postoperative
      days 9 and 14. Statistical analyses were conducted using Student 2-tailed t test.
      Immunofluorescent histology and ASC labeling were also performed to identify
      possible mechanisms. RESULTS: The ADM was successfully prepared, and the
      cytometry analysis and differentiation assay provided the characterization of the
      human ASCs. A marked improvement in granulation thickness was detected in the ADM
      ASC group in comparison with other 3 groups. A significantly increased rate of
      reepithelialization in the ADM-ASC group (80 +/- 6%) compared to the ADM only
      group (60 +/- 7%) was noted on postoperative day 9. The blood vessel density was
      evidently increased in the ADM-ASC group (7.79 +/- 0.40 vessels per field)
      compared to the ADM only group (5.66 +/- 0.23 vessels) on day 14. Cell tracking
      experiments demonstrated that labeled ASCs were colocalized with staining for
      VEGF or endothelial cell maker vWF after the transplantation of ADM-ASCs on
      postoperative day 14. CONCLUSIONS: Adipose-derived stem cells seeded on an ADM
      can enhance wound healing, promote angiogenesis, and contribute to newly formed
      vasculature, and VEGF-expressing ASCs can be detected after transplantation. This
      model could be used to improve the other clinical applications of ASCs and to
      decipher the detailed mechanism by which ASCs interact with wound tissue.

PMID- 23154339
TI  - Fabrication of quantum dot-conjugated collagen/hyaluronic acid porous scaffold.
AB  - A quantum dot (QD)-conjugated collagen-hyaluronic acid (HA) porous scaffold was
      combined with our previously reported animal model of mice inferior epigastric
      flaps and QD infusion to study scaffold angiogenesis. A CdSe/ZnS QD-labeled
      collagen/HA scaffold was fabricated and examined with a confocal microscope. The
      degradation rate of the scaffold was inversely related to 1-ethyl-3-(3
      dimethylaminopropyl)carbodiimide concentration used in cross-linking. There was
      no cytotoxicity of the QDs as determined by MTT colorimetric assay. Results of
      the animal implantation study revealed no difference in acute tissue inflammation
      between scaffolds with or without QD labeling. To study scaffold angiogenesis, we
      infused the implanted QD-conjugated collagen/HA scaffold with QD of different
      fluorescence, which can be simultaneously identified by confocal microscope. By
      these evaluations, we conclude that QD-conjugated collagen/HA porous scaffold is
      not different from that without conjugation and can be used in our animal model
      of scaffold angiogenesis without compromising results.

PMID- 23154340
TI  - MicroRNA signatures in ischemia-reperfusion injury.
AB  - BACKGROUND: MicroRNAs (miRs) are involved in gene expression and function, but
      little is known of their function in ischemia-reperfusion injury (IRI), which
      plays a critical role in flap compromise during microvascular flap surgeries.
      This article aimed to determine the expression profiles of miRs in rat flap
      surgeries after IRI. METHODS: Vessel specimens in rat epigastric flap were
      initially determined for miRs survey after 2 hours of ischemia and 2 hours of
      reperfusion. Their miR expressions were further quantified after 2 hours of
      ischemia and subsequent reperfusion for 2 and 24 hours. RESULTS: Only 3 miRs (miR
      21, miR-193-3p, and miR-210) in rat vessels, but not in flap tissues, were
      significantly up-regulated at 24 hours of reperfusion after 2 hours of ischemia.
      CONCLUSIONS: Our findings provide insights into deregulated expressions of miRs
      in flap surgeries after IRI. They might provide a further therapeutic
      consideration to prevent vascular compromise due to IRI in flap surgeries.

PMID- 23154341
TI  - Herniation of the cervical disk in plastic surgeons.
AB  - Herniations of the cervical disk in plastic surgeons are far more common in
      practice than the paucity of reported cases would indicate. A likely explanation
      may be the peculiar, nonergonomic positions that plastic surgeons must hold
      during surgery while wearing a headlight and loupes. From January 2003 to
      December 2006, at Tri-Service General Hospital, Taiwan, 4 plastic surgeons
      experienced herniations of the cervical disk. Magnetic resonance imaging study
      indicated there was disk herniation or bulging with spinal cord impingement. Two
      plastic surgeons received cervical diskectomy, corpectomy with strut
      reconstruction using titanium cages. These 2 surgeons were symptom-free 2 years
      after their operations. The other 2 plastic surgeons were under conservative
      physical therapy with persistent symptoms. The clinical evidence indicated that
      cervical disk herniation is an occupational hazard in plastic surgeons. To
      prevent prolonged hyperflexion and twisting of the neck, we proposed wearing a
      cervical brace during surgery for the plastic surgeons at Tri-Service-General
      Hospital since January 2008. No more plastic surgeons have experienced herniation
      of the cervical disk since then. The results indicated that wearing a cervical
      brace may be an effective measure to protect plastic surgeons from cervical disk
      disease.

PMID- 23154342
TI  - Mold attacks a beating heart.

PMID- 23154343
TI  - The core teams concept in craniofacial surgery from the start.

PMID- 23154344
TI  - Management of decompressive craniectomy defects:  modern military treatment
      strategies.
AB  - BACKGROUND: Decompressive craniectomy has become a critical and standard life
      saving maneuver in the theater of war. The high number of patients returning with
      large cranial defects and complex craniofacial injuries often involving the upper
      orbits or associated with the sunken skin flaps are a reconstructive challenge.
      We present a review of our treatment protocol highlighting the evolution of
      decompressive craniectomy and the development of a modern cranial defect
      treatment algorithmic approach to reconstruct these difficult clinical cases.
      METHODS: A review of previously published data and current data from our warfare
      treatment unit that reported the treatment of decompressive cranial defects from
      2004 to 2011 was performed. Reported data included mechanism of injury,
      evacuation time, initial Glasgow Coma Scale (GCS), GCS on arrival to the
      continental United States, type of decompressive craniectomy, type of implants
      used for reconstruction, and complications such as implant infections, exposures,
      and removals. Secondary reconstruction techniques used to salvage failed
      cranioplasty cases with free tissue transfers and cranial bone or dermal fat
      grafts as indicated were also reviewed and outcomes were reported. RESULTS: From
      March 2003 to July 2011, more than 200 patients were identified who underwent
      cranioplasty after decompressive craniectomy. Patient average age was
      approximately 25 years (range, 18-53 y), and all patients were male. Average
      follow-up was 870 days (2.4 y). Average GCS at initial presentation was 7 and was
      9 on arrival to the continental United States. Average time to evacuation to the
      continental United States was 6 days. Of all injuries, 46% were associated with
      an improvised explosive device blast. Of the patients, 90% underwent
      hemicraniectomies with the remaining 10% having received bifrontal craniectomies.
      Successful reconstruction and retention of the implant was present in 95% of the
      overall cohort. Contour abnormalities were the most common adverse outcome
      encountered (10% of patients after cranioplasty), whereas infections resulting in
      implant loss (5%) and seizures (<5%) were the most common complications that
      occurred after cranioplasty reconstruction. CONCLUSIONS: Warfare-related
      decompressive craniectomy defects can be safely reconstructed using custom
      alloplastic implants with low morbidity and mortality. Risk factors that increase
      the rate of infection and require implant removal included orbital extension of
      the craniectomy defect, proximity to facial sinuses, and large contour
      abnormalities with corresponding large dead spaces. Staging reconstruction of
      high-risk cranial defects followed by definitive cranial defect reconstruction
      improved the likelihood of implant retention and successful cranioplasty outcome.

PMID- 23154345
TI  - My time with Henry:  40+ years together.

PMID- 23154346
TI  - The Venetian blind technique: modification of the Pi procedure for the surgical
      correction of sagittal synostosis.
AB  - Numerous methods of surgical repair for scaphocephaly (sagittal synostosis) have
      been reported in the literature, from strip craniectomies to more complex methods
      of calvarial vault remodeling. While good cosmesis and restoration of a normal
      anteroposterior diameter may be obtained with these methods, a more rounded
      contour of the biparietal areas is often more difficult to achieve. We describe a
      modification of the Pi technique, described by Jane in 1976, that results in a
      more rounded contour of the biparietal areas. We report our experience on cranial
      vault remodeling for the correction of scaphocephaly in 51 patients from 1998 to
      2011.

PMID- 23154347
TI  - Craniofacial surgery on a personal view.
AB  - Henry Kawamoto Jr and I go back a long way. Our friendship began at the Columbia
      Presbyterian Medical Center. I had just returned from my service obligation after
      interrupting my general surgery residency. I heard that a new resident from
      California had been admitted to our class, and, of course, it was Henry.

PMID- 23154348
TI  - Microsurgical correction of progressive facial hemiatrophy using free
      anterolateral thigh adipofascial flap.
AB  - BACKGROUND: The etiology of progressive facial hemiatrophy is unclear according
      to resent research. The diseases lack effective treatments. The purpose of this
      study was to introduce a technique that restores the cosmetic amelioration
      effectively using free anterolateral thigh adipofascial flap through anastomosis.
      METHODS: From September 1999 to June 2011, a total of 14 patients were subjected
      to correction with revascularized free anterolateral thigh adipofascial flaps at
      the first stage. Some of them performed additional procedures, such as dermal fat
      flap filling, lipoinjection, liposuction, and thinning of the flap, were used for
      secondary minor deformities after the first-stage operation. The donor sites were
      closed primarily without skin grafting or other flap transplantation. RESULTS:
      All of the flaps survived, and the effect is stable during the follow-ups.
      Patients were quite satisfied with the symmetry and plumpness of the
      reconstructed faces. The donor sites were sutured directly and healed at the
      first stage; there were no obvious morbidities and dysfunctions. CONCLUSIONS: The
      anterolateral thigh adipofascial flap can provide adequate tissue with reliable
      blood supply, pliability, ease of revision, and minimal morbidity and dysfunction
      at the donor site. It is a safe, stable, and effective technique for hemifacial
      atrophy.

PMID- 23154349
TI  - Endoscopic delivery of calcium phosphate cement for secondary craniofacial
      reconstruction.
AB  - Contour defects are common following primary craniofacial procedures including
      cranial vault remodeling, fronto-orbital and midface advancements, and complex
      posttraumatic reconstructions. When onlayed as fast-setting pastes, calcium
      phosphate cements (CPCs) have been used to effectively correct contour defects in
      open secondary reconstruction procedures. Here, we describe an endoscopic
      procedure using an injectable CPC and compare surgical outcomes with the open
      technique. A retrospective review was conducted for 36 consecutive patients aged
      3.0-28.9 years (mean, 10.1 years) who underwent secondary craniofacial
      reconstruction over a 3-year period. Patients were stratified into endoscopic or
      open groups depending on the surgical approach utilized. Mean operative time was
      significantly shorter (P < 0.001) for the endoscopic group (64 minutes) than for
      the open group (131 minutes). Similarly, hospital stay was significantly shorter
      (P = 0.005) in the endoscopic group than in the open group. There was also a
      significant difference with respect to cost (P < 0.001), with the endoscopic
      approach resulting in a per-patient cost savings of $2208.05. In conclusion,
      endoscopic delivery of CPC appears to be a safe, efficacious, and cost-effective
      method of performing secondary craniofacial reconstruction, with the additional
      benefits of decreased operative time and shorter postoperative hospital stay when
      compared with an open procedure.

PMID- 23154350
TI  - Nonsyndromic craniosynostosis: the Rady Children's Hospital approach.
AB  - ABSTRACT: Surgical correction for nonsyndromic craniosynostosis has continued to
      evolve over the last century. The criterion standard has remained open correction
      of the cranial deformities, and many techniques have been described that yield
      satisfactory results. However, technology has allowed for minimally invasive
      techniques to be developed with the aid of endoscopic visualization. With proper
      patient selection and the aid of postoperative helmet therapy, there is
      increasing evidence that supports these techniques' safety and efficacy. In this
      article, our purpose was to describe our algorithm for treating nonsyndromic
      craniosynostosis at Rady Children's Hospital.

PMID- 23154352
TI  - Commentary on "Nonsyndromic craniosynostosis: the Rady Children's Hospital
      approach".

PMID- 23154351
TI  - Models of cranial suture biology.
AB  - Craniosynostosis is a common congenital defect caused by premature fusion of
      cranial sutures. The severe morphologic abnormalities and cognitive deficits
      resulting from craniosynostosis and the potential morbidity of surgical
      correction espouse the need for a deeper understanding of the complex etiology
      for this condition. Work in animal models for the past 20 years has been pivotal
      in advancing our understanding of normal suture biology and elucidating
      pathologic disease mechanisms. This article provides an overview of milestone
      studies in suture development, embryonic origins, and signaling mechanisms from
      an array of animal models including transgenic mice, rats, rabbits, fetal sheep,
      zebrafish, and frogs. This work contributes to an ongoing effort toward continued
      development of novel treatment strategies.

PMID- 23154353
TI  - Pierre Robin sequence and Treacher Collins hypoplastic mandible comparison using
      three-dimensional morphometric analysis.
AB  - Pierre Robin sequence and Treacher Collins syndrome are both associated with
      mandibular hypoplasia. It has been hypothesized, however, that the mandible may
      be differentially affected. The purpose of this study was to therefore compare
      mandibular morphology in children with Pierre Robin sequence with children with
      Treacher Collins syndrome using three-dimensional analysis of computed
      tomographic scans. A retrospective analysis was performed identifying children
      with Pierre Robin sequence and Treacher Collins syndrome undergoing computed
      tomography. Three-dimensional reconstruction was performed, and ramus height,
      mandibular body length, and gonial angle were measured. These were then compared
      with those in control children with normal mandibles and with the clinical norms
      corrected for age and sex based on previously published measurements. Mandibular
      body length was found to be significantly shorter for children with Pierre Robin
      sequence, whereas ramus height was significantly shorter for children with
      Treacher Collins syndrome. This resulted in distinctly different ramus height
      mandibular body length ratios. In addition, the gonial angle was more obtuse in
      both the Pierre Robin sequence and Treacher Collins syndrome groups compared with
      the controls. Three-dimensional mandibular morphometric analysis in patients with
      Pierre Robin sequence and Treacher Collins syndrome thus revealed distinctly
      different patterns of mandibular hypoplasia relative to normal controls. These
      findings underscore distinct considerations that must be made in surgical
      planning for reconstruction.

PMID- 23154354
TI  - A personal tribute to a great educator: how Henry Kawamoto influenced my interest
      in facial soft tissue anatomy and changed my plastic surgery career.
AB  - Henry Kawamoto remains one of the most influential craniofacial surgeons of the
      20th century. A Tessier-trained craniofacial surgeon, Dr. Kawamoto has personally
      influenced not only the lives of his patients, but significantly also the lives
      of those craniofacial fellows he educated, passing on the Tessier methodology to
      future generations. This article serves as an anecdote as to how Dr. Kawamoto's
      mentoring influenced a personal understanding of facial soft tissue anatomy,
      leading to improved technical approaches for surgical rejuvenation of the aging
      face.

PMID- 23154355
TI  - Le Fort II osteotomy.
AB  - BACKGROUND: In comparison with the abundant literature on Le Fort I and III
      osteotomies, there is scant information on the Le Fort II osteotomy. Our goal in
      this study was to define the indications and techniques of the elective Le Fort
      II osteotomy. We reviewed our 30-year experience, which is the longest series of
      patients treated with Le Fort II osteotomies at a single institution. METHODS: A
      review of the records of 13 consecutive patients at our institution with a
      diagnosis of Le Fort II was conducted. Data analyzed included demographic
      information, indications, techniques, complications, and combined procedures. On
      the basis of surgical outcomes, a treatment algorithm was created. RESULTS:
      Thirteen patients had a diagnosis of Le Fort II at our institution. Five were
      excluded because of incomplete records or Le Fort II fracture repair. Three
      patients were male, and 5 were female. Their average age was 23 years, and the
      average follow-up was 60 months. Indications included nasomaxillary deviation
      related to unilateral coronal synostosis, hemifacial microsomia, Romberg disease,
      and noncleft nasomaxillary hypoplasia. The average estimated blood loss was 950
      mL. Complications were persistent nasal deviation, temporary nasal obstruction,
      and a hematoma. Complementary procedures included bilateral sagittal split
      osteotomies, bone grafts, Le Fort I osteotomy, and repositioning of the zygoma.
      CONCLUSIONS: On the basis of this review, we have elucidated the indications and
      less invasive techniques of the elective Le Fort II osteotomy. No major
      complications were observed. A management algorithm for performing the Le Fort II
      osteotomy is presented.

PMID- 23154356
TI  - Commentary on "Le Fort II osteotomy".

PMID- 23154357
TI  - Parry-Romberg reconstruction: optimal timing for hard and soft tissue procedures.
AB  - For the treatment of Parry-Romberg syndrome or progressive hemifacial atrophy, we
      studied 3 controversial issues: (1) optimal timing, (2) need for skeletal
      reconstruction, and (3) need for soft tissue (medial canthus/lacrimal duct)
      reconstruction. Patients with Parry-Romberg syndrome (>5 y follow-up) were
      divided into 2 groups: (1) younger than 14 years and (2) 14 years or older (n =
      43). Sex, age, severity of deformity, number of procedures, operative times, and
      augmentation fat volumes were recorded. Physician and patient satisfaction
      surveys (5-point scale) were obtained, preoperative and postoperative three
      dimensional computed tomographic scans were reviewed, and a digital three
      dimensional photogrammetry system was used to determine volume retention. Our
      results indicate that the younger patient group required more procedures compared
      with the older patient group (4.3 versus 2.8); however, the younger group had
      higher patient/family satisfaction scores (3.8 versus 3.0). Skeletal and soft
      tissue reconstruction resulted in improved symmetry score (60% preoperatively to
      93% final) and satisfaction scores (3.4 preoperatively to 3.8 final). Patients
      with Parry-Romberg syndrome required multiple corrective surgeries but showed
      improvements even when beginning before puberty. Soft and hard tissue
      reconstruction was beneficial.

PMID- 23154358
TI  - Obstructive sleep apnea after dynamic sphincter pharyngoplasty.
AB  - INTRODUCTION: In patients who require additional surgery for velopharyngeal
      insufficiency (VPI), a higher incidence of obstructive sleep apnea (OSA) may be
      incurred. Although this phenomenon has been demonstrated with the posterior
      pharyngeal flap, the effect of dynamic sphincter pharyngoplasty (DSP) on OSA is
      less clear. The purposes of this case series were to (1) determine the incidence
      of OSA after DSP, (2) assess the changes in polysomnography after DSP, and (3)
      identify risk factors for the development of OSA after DSP. Our global hypothesis
      is that OSA and VPI exist on a continuum and that speech outcomes should not be
      considered in isolation. METHODS: For a 13-year period, 146 patients with
      idiopathic VPI, submucous cleft palate, cleft palate only, or cleft lip and
      palate underwent DSP for VPI. The diagnosis of OSA was defined as the
      prescription of continuous positive airway pressure therapy by a pediatric sleep
      medicine physician. The incidence of OSA preoperatively and postoperatively was
      compared using Fisher exact test. When available, preoperative and postoperative
      apnea-hypopnea indices (AHIs) were compared using the pairwise, 2-tailed,
      Student's t-test. Patient factors, such as obesity (body mass index >= 95th
      percentile), the presence of a craniofacial syndrome, surgical history, and a
      preexisting OSA diagnosis, were noted. A multiple logistic regression was
      performed to elucidate risk factors for the development of OSA. RESULTS: The
      average age at surgery was 9.2 years (range, 4-40 y), and the mean follow-up time
      was 4.5 years (range, 1 mo to 12 y). The incidence of OSA increased after DSP,
      from 2 to 33 patients (1.4%-22%, respectively; P = 0.05). In 23 patients (16%),
      both preoperative and postoperative AHIs were available. There was a significant
      increase in AHI after DSP, from 3.1 to 8.4 episodes per hour of sleep (P =
      0.001). Previous tonsillectomy/adenoidectomy was predictive of OSA after DSP
      (relative risk = 2.4; P = 0.04). CONCLUSIONS: We report an increased incidence of
      OSA and higher-than-average AHIs postoperatively after DSP. Preoperative
      tonsillectomy/adenoidectomy predicted the development of OSA after DSP. A high
      index of suspicion for development of OSA must be maintained in patients who
      undergo secondary speech operations for VPI. Clinical screening for OSA should be
      used in this population, with a low threshold for polysomnographic evaluation.
      The surgeon must be wary that improvements in speech after DSP may change airway
      dynamics and increase the risk of OSA.

PMID- 23154359
TI  - Commentary on "Obstructive sleep apnea after dynamic sphincter pharyngoplasty".

PMID- 23154360
TI  - Thoughts on the Davies repair of unilateral cleft lip.
AB  - The Davies Z-plasty repair of the unilateral cleft lip can generate adequate lip
      height with little transverse tightness and should be considered in the presence
      of a vertically short lateral lip. Separate repair of the orbicularis muscle may
      contribute to good long-term lip height and shape. It is possible to revise the Z
      repair to increase height.

PMID- 23154361
TI  - Immediate mandibular distraction in mandibular hypoplasia and upper airway
      obstruction.
AB  - Distraction osteogenesis of the mandible has become an alternative to
      tracheostomy in infants and children who present with upper airway obstruction
      due to micrognathia. To avoid prolonged intubation during distraction, we have
      implemented a protocol of immediate distraction at the time of distractor
      placement, which results in acute airway improvement. Over 2 years, 22 patients
      with micrognathia and severe airway obstruction have undergone mandibular
      distractor placement. Indications for surgery were apnea and desaturations with
      feeding. Resorbable distraction devices were placed bilaterally and activated to
      5 to 8 mm. Recombinant human bone morphogenetic protein 2 was placed in the gap.
      Distraction was implemented at postoperative day 2 at 2 mm/d. Forty-four
      distraction devices were placed in 22 patients (68% male, 32% female) with a mean
      age of 24.1 months (range, 3 days to 5.5 years). The average distance of
      distraction performed in the operating room was 5 mm. The average total
      distraction was 24 mm performed over 12 days. Overall, 89% of patients were
      extubated after distractor placement in the operating room. Two patients with
      difficult intubations were extubated 7 days later in the operating room with
      otolaryngology. Of the 4 tracheostomy patients, 1 patient was decannulated,
      whereas 3 patients are pending postoperative sleep studies. One patient had a
      minor wound complication. Tracheostomy and prolonged intubation in patients with
      mandibular hypoplasia have significant morbidity and mortality. We have
      implemented a successful protocol of immediate distraction in the operating room
      with placement of bone morphogenetic protein. Immediate distraction appears to be
      an effective method of avoiding postoperative intubation and tracheostomy.

PMID- 23154362
TI  - Valuing and selling a practice.
AB  - Surgeons, as they contemplate retirement, wrongly believe that their practices do
      not have financial value. In fact, a well-organized efficiently functioning
      office with an emphasis on excellent service in combination with a constant
      stream of patients make it financially ideal for the new surgeon. Being able to
      assume such a practice can be a very smart financial decision. The practice's
      worth can be determined by a careful analysis of the practice financials and an
      evaluation of the functioning of the office and employees. Purchasing such a
      practice can be, economically, a very smart move by a new surgeon. Payments are
      made over time at a rate that allows the surgeon to make a good living, leaving
      him with real equity once the payments are complete. The departing surgeon, who
      had spent years building this successful practice, gets some of this value back
      in the form of an income stream to supplement his retirement. This process should
      be considered in virtually every case. Do not just "close the door."

PMID- 23154364
TI  - Commentary on "Incisions for orbital floor exploration".

PMID- 23154363
TI  - Incisions for orbital floor exploration.
AB  - Incisions used for orbital floor exploration continues to remain a topic of
      controversy. Historically, 3 incisions have been used for orbital floor repair:
      transconjunctival, subciliary, and subtarsal. Past studies have attempted to
      stratify the superiority of one incision over the others. Insufficient level of
      evidence and inconsistent methodology have lead to inconclusive data. Our authors
      performed a systematic review of literature to assess the quality of evidence in
      literature and recommend guidelines for incisions for repairing orbital
      fractures. Thirty-one articles were identified, comprising a total of 4688
      incisions. Technique along with individual benefits and complication profiles for
      each incision is reviewed. Objectivity and follow-up time intervals are necessary
      parameters for evaluating incisions for orbital floor exploration to further
      define guidelines.

PMID- 23154365
TI  - Materials used for reconstruction after orbital floor fracture.
AB  - Advances in biotechnology continue to introduce new materials for reconstruction
      of orbital floor fractures. Which material is best fit for orbital floor
      reconstruction has been a controversial topic. Individual surgeon preferences
      have been supported by inconsistent inconclusive data. The purpose of this study
      was to assess and analyze published evidence supporting various materials used
      for orbital floor reconstruction and to develop a decision-making algorithm for
      clinical application. A systematic literature review was performed from which 48
      studies were selected after primary and secondary screening based on set
      inclusion and exclusion criteria. This cumulatively included 3475 separate
      orbital floor reconstructions. Results revealed risk and benefit profiles for all
      materials. Autologous calvarial bone grafts, porous polyethylene, and
      polydioxanone (PDS) were most widely used for orbital floor reconstruction.
      Increased infection rates were reported with polyglactin 910/PDS composites and
      silastic rubber. Ocular motility was reduced most with lyophilized dura and PDS.
      Preoperative and postoperative rates for diplopia and enophthalmos varied among
      the materials. In conclusion, our results revealed continued inadequate evidence
      to exclusively support the use of any one biomaterial/implant for orbital floor
      reconstruction. Results have served to create a decision-making algorithm for
      clinical application. Our authors propose certain parameters for future studies
      seeking to demonstrate a comparison between 2 or more materials for orbital floor
      reconstruction.

PMID- 23154366
TI  - More to this study than meets the eye.

PMID- 23154367
TI  - The Kawamoto epilogue: a prologue for craniofacial surgery.

PMID- 23154368
TI  - Vector control in internal midface distraction using temporary anchorage devices.
AB  - Le Fort III and monobloc distraction osteogenesis serve as the primary surgical
      treatment for children with severe midface hypoplasia. The orbital retrusion and
      class III malocclusion of patients with midface hypoplasia is best addressed with
      bodily advancement of the midface segment parallel to the cephalometric Frankfort
      horizontal plane. Use of internal distraction devices allows for advancement of
      the midface without extensive external hardware but comes at the cost of less
      vectorial control, resulting in a distraction vector that can cause a clockwise
      rotation of the entire midface or frontofacial component creating hollow
      appearing orbits. To counteract this clockwise rotation, we have developed a
      technique using orthodontic microimplants to anchor interarch class III
      relationship elastics. We report our experiences with this technique on a
      cadaveric model and as a case series of 17 patients who underwent midface
      distraction. A Le Fort III distraction procedure was carried out on a cadaver,
      and the orbital height was measured at 0-, 10-, and 20-mm distraction advancement
      with and without elastics in a class III relationship. Improvement of both
      subjective hollow appearance of the orbits and objective measurement of the
      orbital height with class III relationship elastics demonstrated the efficacy of
      class III relationship elastics in counteracting the clockwise rotation of the
      midface segment. A review of 17 patients with midface or frontofacial hypoplasia
      treated with Le Fort III or monobloc distraction with simultaneous microimplant
      anchored class III relationship elastics revealed correction of malocclusion and
      improved midface projection without significant increase in vertical height of
      the orbits.

PMID- 23154369
TI  - What K would do.

PMID- 23154370
TI  - Separation of craniopagus conjoined twins with a staged approach.
AB  - The separation of craniopagus conjoined twins is a very rare and complex
      challenge. As with many rare challenges, it presents initially as a deceptively
      simple problem requiring only the most basic clinical techniques. As in many
      reconstructive problems, this paradigm mandates that the neurosurgical team
      performs the separation with the plastic surgeons providing closure at the end of
      the separation. Historically, these approaches have included, as with the
      separation of many other types of conjoined twins, the use of tissue expansion
      before separation followed by separation surgery. In the best hands, at the most
      capable medical centers, the mortality reported in the literature for the past 50
      years is greater than 50%. Craniofacial surgery frequently demands a coordinated
      effort between plastic surgery and neurosurgery and many other specializations;
      separating craniopagus twins takes this coordination to a stratospheric level. It
      is, however, this coordination that is of paramount importance. Success clearly
      requires an understanding of the complex interrelationship between the
      "separation" and the "reconstruction" and that decisions made for 1 aspect of the
      surgery will have a profound impact on another aspect of the surgery. The impact
      can be disastrous or, if planned well, can be advantageous.We were contacted to
      evaluate craniopagus conjoined male infant twins for separation. Radiographic
      studies suggested that the brains were separate, and their medical team suggested
      that they were "fit for separation." We reviewed the literature and reviewed our
      colleagues' experiences with similar cases around the world. It became clear that
      whether separation had been unsuccessful or successful, a variety of issues
      accompanied surgery as follows: (1) massive intraoperative hemorrhage, (2)
      cerebral edema, (3) venous infarcts, (4) swelling of flaps, and (5) dehiscence of
      repairs with cerebrospinal fluid (CSF) leak, meningitis, or brain exposure.
      Although the initial plan was to separate the twins in the same fashion as in
      previous cases (ie, single-stage separation surgery preceded by tissue expansion
      of the scalp), it was clear that this approach increases cerebral venous pressure
      during the separation component of surgery and therefore set up a cascade of
      events favoring failure rather than success. Wishing to favor success, we elected
      to design an open-ended multistaged separation to improve venous collateral
      circulation. We believe that this would improve venous drainage, prevent
      increased venous pressure, diminish cerebral edema, and favor the integrity of
      the dura and flap repair that would in turn lessen the risk of CSF leak. The
      stages would also allow the twins to recover from each stage before progressing
      to the next stage while continuing to receive nutritional support and physical
      therapy. Four major stages for 9 1/2 months led to their successful separation.
      There has been no CSF leak or meningitis. To our knowledge, this technique has
      since been applied to 2 other sets of craniopagus with similar outcomes.A review
      of the pertinent literature, our rationale, and methodology are discussed in this
      article.

PMID- 23154371
TI  - Transient oblong anisocoria and orbital surgery.
AB  - We present a rare case of transient oblong (segmental) anisocoria occurring at
      the time of limited orbital surgery. Observation of this previously undescribed
      phenomenon prompted us to review the relevant anatomy and physiology of the iris
      and the pharmacokinetics of lidocaine as it pertains to surgery in the region of
      the eyelids and the orbit.

PMID- 23154372
TI  - Commentary on "Transient oblong anisocoria and orbital surgery".

PMID- 23154373
TI  - Bregmatic wormian bone and metopic synostosis.
AB  - We present a case of a 14-week-old girl with metopic synostosis and an incidental
      finding of a large, pentagonal bregmatic wormian bone. No prior photographic
      evidence of this combination of rare findings exists. An extensive review of the
      incidence, etiology, and significance of these unusual supernumerary cranial
      bones is provided in this study.

PMID- 23154374
TI  - Photoelastic analysis of stresses transmitted by universal cast to long abutment
      on implant-supported single restorations under static occlusal loads.
AB  - OBJECTIVES: The aim of this study was to compare the stresses resulting from
      cemented or screw-retained dental prostheses using universal cast to long
      abutment by the photoelastic method. MATERIAL AND METHODS: A photoelastic resin
      model was fabricated to simulate a segment of the mandibular arch with resin
      replicas of a first premolar and a second molar, and two 3.75 * 11-mm implants
      replacing the second premolar and the first molar. Vertical static loads were
      individually applied on the occlusal surface of the premolar and the molar (5
      kgf) and simultaneously on both crowns (10 kgf). RESULTS: Results found variable
      stress patterns around each implant and concentrated stresses in the individually
      loaded crowns. Force transfer characteristics of each situation and
      quantification of the isochromatic fringes were evaluated. CONCLUSIONS: Within
      the limitations of this study and based on the results obtained for implant
      supported prosthesis with internal hexagon connection/universal cast to long
      abutment, it could be concluded that single adjacent screw-retained prosthetic
      restorations lead to higher stresses around the implants when compared with
      cement-retained restorations.

PMID- 23154375
TI  - Humanitarian cleft care in Southeast Asia: military-civilian partnerships and the
      role of the US Navy ship Mercy.
AB  - The primary mission of the US Navy (USN) is to maintain superior naval forces
      capable of winning wars, deterring aggression, and maintaining freedom of the
      seas. However, a major core capability of the present-day USN includes the
      ability to effectively and rapidly provide humanitarian assistance and disaster
      response whenever the need arises. Occurring annually since 2006, Pacific
      Partnership is an ongoing USN operation that aims to strengthen regional
      alliances and improve delivery of humanitarian assistance and disaster relief. A
      major focus of Pacific Partnership 2010 was the delivery of medical care to
      underserved communities in the region. A significant portion of the medical
      mission was specifically directed toward the treatment of patients with cleft lip
      and palate. As the main operational platform, the USN Ship Mercy provided an
      unparalleled environment in which to provide state-of-the-art multidisciplinary
      treatment to patients with cleft lip and palate. With the cooperation of host
      nations and locally active nongovernmental organizations, a sustainable model for
      providing treatment for cleft lip and palate can be developed.

PMID- 23154376
TI  - Soft tissue correction of craniofacial microsomia and progressive hemifacial
      atrophy.
AB  - BACKGROUND: Moderate to severe soft tissue deficits can exist with craniofacial
      microsomia or progressive hemifacial atrophy. The authors reviewed the surgical
      correction of these defects, including serial autologous fat grafting and
      parascapular free tissue transfer. METHODS: Recently treated patients at the
      Institute of Reconstructive Plastic Surgery at NYU Medical Center were
      identified. Patients with microvascular free flap underwent reconstruction with
      parascapular flaps. These flaps have been modified from previously reported
      inframammary extended circumflex scapular flaps. Demographic information,
      operative interventions, complications, and outcomes were reviewed and analyzed.
      The clinical outcomes of these patients were compared with previously reported
      patients who underwent serial autologous fat grafting. RESULTS: Five patients
      were recently treated with 7 parascapular flaps. The mean age of the patients at
      the time of parascapular flap reconstruction was 13.1 years. These were compared
      to those previously reported who have undergone serial autologous fat grafting.
      The mean number of procedures was less for the free tissue transfer cohort. There
      were no microvascular complications because all free flaps survived. One patient
      had wound dehiscence of the donor site managed with local wound care and healing
      by secondary intention. CONCLUSIONS: For patients undergoing multiple-stage
      reconstruction of craniofacial microsomia, serial fat grafting is a useful tool
      for soft tissue reconstruction. Alternatively, in those patients with isolated
      soft tissue hypoplasia, such as progressive hemifacial atrophy, microvascular
      free tissue transfer is a safe and efficient option.

PMID- 23154377
TI  - Accelerating surgical training and reducing the burden of surgical disease in
      Haiti before and after the earthquake.
AB  - In general, university-based global health initiatives have tended to focus on
      expanding access to primary care. In the past, surgical programs may have been
      characterized by sporadic participation with little educational focus. However,
      there have been some notable exceptions with plastic surgery volunteer missions.
      We offer another model of regularly scheduled surgical trips to rural Haiti in
      plastic and general surgery. The goal of these trips is to reduce the burden of
      surgical disease and ultimately repair every cleft lip/palate in Haiti. Another
      principal objective is to accelerate the training of American residents through
      increased case load and personal interaction with attending surgeons in a
      concentrated period. Diversity of the case load and the overall number of
      surgeries performed by residents in a typical surgical trip outpaces the
      experiences available during a typical week in an American hospital setting. More
      importantly, we continue to provide ongoing training to Haitian nurses and
      surgeons in surgical techniques and postoperative care. Our postoperative
      complication rate has been relatively low. Our follow-up rates have been lower
      than 70% despite intensive attempts to maintain continued communication with our
      patients. Through our experiences in surgical care in rural Haiti, we were able
      to quickly ramp up our trauma and orthopedic surgical care immediately after the
      earthquake. Project Medishare and the University of Miami continue to operate a
      trauma and acute care hospital in Port au Prince. The hospital provides ongoing
      orthopedic, trauma, and neurosurgical expertise from the rotating teams of
      American surgeons and training of Haitian surgeons in modern surgical techniques.
      We believe that surgical residencies in the United States can improve their
      training programs and reduce global surgical burden of disease through consistent
      trips and working closely with country partners.

PMID- 23154378
TI  - Optimizing the timing and technique of Treacher Collins orbital malar
      reconstruction.
AB  - The optimal timing and treatment of Treacher Collins syndrome with regard to
      zygomatico-orbital osseous reconstruction has not been fully established. Osseous
      reconstruction performed at an early age may result in bone graft resorption;
      however, delays in surgical improvement may result in adverse psychosocial
      effects on the patient. To study the optimal age for reconstruction clinically,
      we examined 3 age groups based on timing of malar and eyelid reconstruction using
      a three-dimensional computed tomographic scan and three-dimensional photometric
      volume assessment. In addition, we collected outcome assessments from
      parents/patients using satisfaction surveys. Of 73 patients with Treacher Collins
      at the University of California Los Angeles Craniofacial Clinic, 45 had malar
      reconstruction, complete records, and were available for study. The patients were
      separated into 3 groups: (1) very young = 0 to 5 years, (2) mid-childhood = 6 to
      12 years, and (3) adolescent/adult 13 years and older. As hypothesized, the 0 to
      5 age group experienced the greatest percentage of complete bony resorption (77%)
      compared with the 6 to 12 age group (only 4%) and the 13 and older age group
      (0%). Interestingly, the 0 to 5 age group experienced the highest parent/patient
      satisfaction, possibly owing to better psychosocial experience. When dealing with
      treatment plans for patients with Treacher Collins, patients, parents, and
      physicians must balance the benefits of early surgical intervention, such as
      improved psychologic well-being, with the disadvantages of having to undergo a
      greater number of procedures, such as fat grafting after malar bone graft
      resorption.

PMID- 23154379
TI  - Orthognathic surgery for obstructive sleep apnea:  applying the principles to new
      horizons in craniofacial surgery.
AB  - This article is dedicated to the senior author Dr. Henry K. Kawamoto, Jr, who
      pioneered the use of orthognathic surgery to treat severe obstructive sleep apnea
      in 1981. Since that time, his techniques for maxillomandibular advancement have
      been revised and expanded for improved surgical success. Obstructive sleep apnea
      is a growing public health concern because it can cause hypertension, cardiac
      arrhythmias, heart attack, stroke, and, in rare circumstances, sudden death if
      untreated. When less invasive options fail such as weight loss or dental devices
      for mandibular repositioning, maxillomandibular advancement is a valuable
      treatment option for severe obstructive sleep apnea.

PMID- 23154382
TI  - Experiences of early users of direct-to-consumer genomics in Switzerland: an
      exploratory study.
AB  - AIMS: This study explores attitudes, motivations and self-reported impact in
      connection with direct-to-consumer (DTC) genomic testing amongst a group of life
      scientists in Switzerland. METHODS: Data were collected through: (1) a self
      completion online questionnaire, and (2) semi-structured qualitative interviews.
      Forty participants completed the questionnaire and 10 were interviewed. RESULTS:
      Curiosity was mentioned as the primary reason for undergoing testing, while less
      significance was attributed to receiving actionable health information. The
      opportunity to contribute to research ranked high as a motive for testing.
      Overall, participants assessed their experience with the test as positive and
      were willing to recommend it to others. Some reported that the testing had an
      impact on how they view their health, but only a third of participants planned on
      showing the results to health practitioners. Participants consistently referred
      to 'fun' when describing several aspects of the testing experience. The 'fun
      factor' manifested itself in different phases of the process, including the
      motivation for taking the test, receiving the information and putting the test
      results to use (including sharing and discussing it with others). This finding
      suggests the need to further explore the concept of personal utility in DTC
      genomics. CONCLUSIONS: Although this group is not representative of the broader
      population due to both their scientific expertise and their willingness to try
      out a controversial new technology, their experiences provide valuable insights
      into the role of personal curiosity and altruism (fostering medical research) as
      motivations for testing and the utility attributed to both.

PMID- 23154380
TI  - It does not look odd to me: perceptual impairments and eye movements in amnesic
      patients with medial temporal lobe damage.
AB  - Studies of people with memory impairments have shown that a specific set of brain
      structures in the medial temporal lobe (MTL) is vital for memory function.
      However, whether these structures have a role outside of memory remains
      contentious. Recent studies of amnesic patients with damage to two structures
      within the MTL, the hippocampus and the perirhinal cortex, indicated that these
      patients also performed poorly on perceptual tasks. More specifically, they
      performed worse than controls when discriminating between objects, faces and
      scenes with overlapping features. In order to investigate whether these
      perceptual deficits are reflected in their viewing strategies, we tested a group
      of amnesic patients with MTL damage that included the hippocampus and perirhinal
      cortex on a series of oddity discrimination tasks in which they had to select an
      odd item from a visual array. Participants' eye movements were monitored
      throughout the experiment. Results revealed that patients were impaired on tasks
      that required them to discriminate between items that shared many features, and
      tasks that required processing items from different viewpoints. An analysis of
      their eye movements revealed that they exhibited a similar viewing pattern as
      controls: they fixated more on the target item on trials answered correctly, but
      not on trials answered incorrectly. In addition, their impaired performance was
      not explained by an abnormal viewing-strategy that assessed their use of working
      memory. These results suggest that the perceptual deficits in the MTL patients
      are not a consequence of abnormal viewing patterns of the objects and scenes, but
      instead, could involve an inability to bind information gathered from several
      fixations into a cohesive percept. These data also support the view that MTL
      structures are important not only for long-term memory, but are also involved in
      perceptual tasks.

PMID- 23154383
TI  - Cocktail blood biomarkers: prediction of clinical outcomes in patients with acute
      ischemic stroke.
AB  - BACKGROUND: Timely prediction of stroke outcomes is important for proper
      personalized treatment. In the present study, we aimed to develop cocktail blood
      biomarkers to increase prediction efficiency using a combination of hemostasis,
      inflammatory and repair-related biomarkers. METHODS: 105 patients suffering from
      acute ischemic stroke were divided into good outcome group and poor outcome group
      by modified Rankin Scale (mRS). Cytokines including CD40L, IFN-gamma, IL-1alpha,
      IL-1beta, IL-6, IL-8, IL-17 and TNF-alpha, as well as hemostasis markers
      fibrinogen, fibrin degradation products (FDP), D-dimer, tissue plasminogen
      activator, and plasminogen activation inhibitor-1 in plasma were examined by
      ELISA. Repair-related biomarker microRNA-210 (miR-210) was measured by real-time
      PCR. The prediction efficiency was explored by receiver operator characteristic
      analysis. RESULTS: We demonstrated that FDP, IL-6 and miR-210 levels were closely
      associated with mRS in stroke patients. The prediction sensitivity of FDP, IL-6
      and miR-210 for stroke outcome was 72.0, 86.7 and 82.5%, respectively. Using a
      combination of biomarkers including FDP, IL-6 and miR-210, the prognostic
      sensitivity of ischemic stroke increased to 95.2%. CONCLUSION: The combination of
      FDP, IL-6 and miR-210 has a high sensitivity for predicting stroke recovery, it
      serves as a potential cocktail blood biomarker. It provides a novel approach for
      stroke prognosis.

PMID- 23154384
TI  - Effect of embryo density on in vitro development and gene expression in bovine in
      vitro-fertilized embryos cultured in a microwell system.
AB  - To identify embryos individually during in vitro development, we previously
      developed the well-of-the-well (WOW) dish, which contains 25 microwells. Here we
      investigated the effect of embryo density (the number of embryos per volume of
      medium) on in vitro development and gene expression of bovine in vitro-fertilized
      embryos cultured in WOW dishes. Using both conventional droplet and WOW culture
      formats, 5, 15, and 25 bovine embryos were cultured in 125 MUl medium for 168 h.
      The blastocysts at Day 7 were analyzed for number of cells and expression of ten
      genes (CDX2, IFN-tau, PLAC8, NANOG, OCT4, SOX2, AKR1B1, ATP5A1, GLUT1 and IGF2R).
      In droplet culture, the rates of formation of >4-cell cleavage embryos and
      blastocysts were significantly lower in embryos cultured at 5 embryos per droplet
      than in those cultured at 15 or 25 embryos per droplet, but not in WOW culture.
      In both droplet and WOW culture, developmental kinetics and blastocyst cell
      numbers did not differ among any groups. IFN-tau expression in embryos cultured
      at 25 embryos per droplet was significantly higher than in those cultured at 15
      embryos per droplet and in artificial insemination (AI)-derived blastocysts.
      Moreover, IGF2R expression was significantly lower in the 25-embryo group than in
      the 5-embryo group and in AI-derived blastocysts. In WOW culture, these
      expressions were not affected by embryo density and were similar to those in AI
      derived blastocysts. These results suggest that, as compared with conventional
      droplet culture, in vitro development and expression of IFN-tau and IGF2R in the
      microwell system may be insensitive to embryo density.

PMID- 23154385
TI  - Ascorbic acid improves the developmental competence of porcine oocytes after
      parthenogenetic activation and somatic cell nuclear transplantation.
AB  - In this study, a dose-response assessment was performed to understand the
      relation between supplementation of media with L-ascorbic acid or vitamin C and
      porcine oocyte maturation and the in vitro development of parthenotes (PA) and
      handmade cloned (HMC) embryos. Various concentrations (0, 25, 50 and 100 MUg/ml)
      of vitamin C supplemented in in vitro maturation (IVM) and culture (IVC) media
      were tested. None of these vitamin C additions affected nuclear maturation of
      oocytes, yet supplementation at 50 MUg/ml led to significantly increased
      intracellular glutathione (GSH) levels and reduced reactive oxygen species (ROS).
      When cultured in IVM- and/or IVC-supplemented media, the group supplemented with
      50 MUg/ml of vitamin C showed improved cleavage rates, blastocyst rates and total
      cell numbers per blastocyst (P<0.05) compared with other groups (control, 25
      MUg/ml and 100 MUg/ml). In contrast, supplementation with 50 MUg/ml vitamin C
      decreased (P<0.05) the apoptosis index as compared with the groups supplemented
      with 100 MUg/ml. In addition, even with a lower blastocyst rate to start with
      (37.6 vs. 50.3%, P<0.05), supplementation of HMC embryos with vitamin C
      ameliorated their blastocyst quality to the extent of PA embryos as indicated by
      their total cell numbers (61.2 vs. 59.1). Taken together, an optimized
      concentration of vitamin C supplementation in the medium not only improves
      blastocyst rates and total cell numbers but also reduces apoptotic indices,
      whereas overdosages compromise various aspects of the development of parthenotes
      and cloned porcine embryos.

PMID- 23154386
TI  - Capillary electrophoresis with three-color fluorescence detection for the
      analysis of glycosphingolipid metabolism.
AB  - A capillary electrophoresis system with an ultrasensitive three-color laser
      induced fluorescence detector was constructed for the simultaneous measurement of
      glycosphingolipids conjugated with a family of BODIPY fluorophores. The compounds
      were separated by capillary electrophoresis and detected by laser-induced
      fluorescence excited within a sheath-flow cuvette. Diode-pumped solid-state
      lasers operating at 473 nm and 532 nm, and a diode laser operating at 633 nm were
      used to excite glycosphingolipids tagged with BODIPY-FL, BODIPY-TMR, and BODIPY
      650/665 fluorophores. Detection limits were 34 +/- 1 molecules, 67 +/- 7
      molecules, and 36 +/- 13 molecules of BODIPY-FL, BODIPY-TMR, and BODIPY-650/665
      labeled glycosphingolipids. Separation efficiencies were typically one million
      theoretical plates. To test the ability of the system to analyze cellular
      contents in an in vitro biological model, differentiated PC12 cells were co
      incubated with BODIPY-FL, BODIPY-TMR, and BODIPY-650/665 labeled lactosylceramide
      substrates. Cells were homogenized. The metabolic products originating from the
      glycosphingolipid substrates were simultaneously analyzed using the system.

PMID- 23154388
TI  - Recruitment of Grb2 and SHIP1 by the ITT-like motif of TIGIT suppresses granule
      polarization and cytotoxicity of NK cells.
AB  - Activating and inhibitory receptors control natural killer (NK) cell activity. T
      cell immunoglobulin and ITIM (immunoreceptor tyrosine-based inhibition motif)
      domain (TIGIT) was recently identified as a new inhibitory receptor on T and NK
      cells that suppressed their effector functions. TIGIT harbors the immunoreceptor
      tail tyrosine (ITT)-like and ITIM motifs in its cytoplasmic tail. However, how
      its ITT-like motif functions in TIGIT-mediated negative signaling is still
      unclear. Here, we show that TIGIT/PVR (poliovirus receptor) engagement disrupts
      granule polarization leading to loss of killing activity of NK cells. The ITT
      like motif of TIGIT has a major role in its negative signaling. After TIGIT/PVR
      ligation, the ITT-like motif is phosphorylated at Tyr225 and binds to cytosolic
      adapter Grb2, which can recruit SHIP1 to prematurely terminate
      phosphatidylinositol 3-kinase (PI3K) and MAPK signaling, leading to
      downregulation of NK cell function. In support of this, Tyr225 or Asn227 mutation
      leads to restoration of TIGIT/PVR-mediated cytotoxicity, and SHIP1 silencing can
      dramatically abolish TIGIT/PVR-mediated killing inhibition.

PMID- 23154387
TI  - The Ca2+/Mn2+ ion-pump PMR1 links elevation of cytosolic Ca(2+) levels to alpha
      synuclein toxicity in Parkinson's disease models.
AB  - Parkinson's disease (PD) is characterized by the progressive loss of dopaminergic
      neurons, which arises from a yet elusive concurrence between genetic and
      environmental factors. The protein alpha-synuclein (alphaSyn), the principle
      toxic effector in PD, has been shown to interfere with neuronal Ca(2+) fluxes,
      arguing for an involvement of deregulated Ca(2+) homeostasis in this neuronal
      demise. Here, we identify the Golgi-resident Ca(2+)/Mn(2+) ATPase PMR1 (plasma
      membrane-related Ca(2+)-ATPase 1) as a phylogenetically conserved mediator of
      alphaSyn-driven changes in Ca(2+) homeostasis and cytotoxicity. Expression of
      alphaSyn in yeast resulted in elevated cytosolic Ca(2+) levels and increased cell
      death, both of which could be inhibited by deletion of PMR1. Accordingly, absence
      of PMR1 prevented alphaSyn-induced loss of dopaminergic neurons in nematodes and
      flies. In addition, alphaSyn failed to compromise locomotion and survival of
      flies when PMR1 was absent. In conclusion, the alphaSyn-driven rise of cytosolic
      Ca(2+) levels is pivotal for its cytotoxicity and requires PMR1.

PMID- 23154389
TI  - Regulation of endodermal differentiation of human embryonic stem cells through
      integrin-ECM interactions.
AB  - Many cellular responses during development are regulated by interactions between
      integrin receptors and extracellular matrix proteins (ECMPs). Although the
      majority of recent studies in human embryonic stem cell (hESC) differentiation
      have focused on the role of growth factors, such as FGF, TGFbeta, and WNT,
      relatively little is known about the role of ECMP-integrin signaling in this
      process. Moreover, current strategies to direct hESC differentiation into various
      lineages are inefficient and have yet to produce functionally mature cells in
      vitro. This suggests that additional factors, such as ECMPs, are required for the
      efficient differentiation of hESCs. Using a high-throughput multifactorial
      cellular array technology, we investigated the effect of hundreds of ECMP
      combinations and concentrations on differentiation of several hPSC lines to
      definitive endoderm (DE), an early embryonic cell population fated to give rise
      to internal organs such as the lung, liver, pancreas, stomach, and intestine.
      From this screen we identified fibronectin (FN) and vitronectin (VTN) as ECMP
      components that promoted DE differentiation. Analysis of integrin expression
      revealed that differentiation toward DE led to an increase in FN-binding integrin
      alpha5 (ITGA5) and VTN-binding integrin alphaV (ITGAV). Conditional short hairpin
      RNA-mediated knockdown of ITGA5 and ITGAV disrupted hESC differentiation toward
      DE. Finally, fluorescence-based cell sorting for ITGA5 and ITGAV significantly
      enriched cells with gene expression signatures associated with DE, demonstrating
      that these cell surface proteins permit isolation and enrichment of DE from
      hESCs. These data provide evidence that FN and VTN promote endoderm
      differentiation of hESCs through interaction with ITGA5 and ITGAV, and that ECMP
      integrin interactions are required for hESC differentiation into functionally
      mature cells.

PMID- 23154390
TI  - Surface chemistry-mediated penetration and gold nanorod thermotherapy in
      multicellular tumor spheroids.
AB  - We investigated the penetration and thermotherapy efficiency of different surface
      coated gold nanorods (Au NRs) in multicellular tumor spheroids. The current data
      show that negatively charged Au NRs, other than positively charged Au NRs, can
      penetrate deep into the tumor spheroids and achieve a significant thermal
      therapeutic benefit.

PMID- 23154391
TI  - A double-blinded randomized controlled trial of laparoendoscopic single-site
      access versus conventional 3-port appendectomy.
AB  - OBJECTIVE: The aim of the current study was to perform a multicentered
      prospective double-blinded randomized controlled trial comparing laparoendoscopic
      single-site access (LESS) versus conventional three-port laparoscopic
      appendectomy (TPLA). BACKGROUND: The clinical benefits and disadvantages of LESS
      appendectomy are uncertain. METHODS: Between October 2009 and March 2011,
      consecutive patients admitted with clinical or radiological evidence of
      appendicitis were randomly assigned to receive either LESS or TPLA. The main
      outcome measurement was overall pain score. Secondary outcome measurements
      included operative time, conversion rates, morbidity rates, activity pain scores,
      activity scores, patient satisfaction, and cosmesis scores. RESULTS: During the
      study period, 200 patients were recruited to the study. There were no significant
      differences in the morbidity rates, operative time, conversion rates, and
      postoperative recovery. There were also no differences in the overall pain score
      and pain score at rest. However, patients in the LESS group experienced
      significantly more pain upon coughing or standing and required more intravenous
      analgesics (P = 0.001, 0.038, and 0.035, respectively). Wound cosmesis and
      satisfaction scores on the contrary were better in the LESS group (P = 0.002 and
      P = 0.052). No differences in the quality-of-life assessments were present at 2
      weeks after operation. CONCLUSIONS: LESS and conventional appendectomy resulted
      in similar perioperative outcomes. However, LESS appendectomy resulted in worst
      pain scores upon exertion and required a higher dosage of intravenous analgesics
      when compared with TPLA. On the contrary, wound cosmesis and satisfaction scores
      were better in the LESS group. Hence, adoption of the technique for appendectomy
      will depend on patient preferences and the presence of local expertise.

PMID- 23154392
TI  - Long-term outcomes of the australasian randomized clinical trial comparing
      laparoscopic and conventional open surgical treatments for colon cancer: the
      Australasian Laparoscopic Colon Cancer Study trial.
AB  - OBJECTIVE: : We report a multicentered randomized controlled trial across
      Australia and New Zealand comparing laparoscopic-assisted colon resection (LCR)
      with open colon resection (OCR) for colon cancer. BACKGROUND: : Colon cancer is a
      significant worldwide health issue. This trial investigated whether the short
      term benefits associated with LCR for colon cancer could be achieved safely,
      without survival disadvantages, in our region. METHODS: : A total of 601 patients
      with potentially curable colon cancer were randomized to receive LCR or OCR.
      Primary endpoints were 5-year overall survival, recurrence-free survival, and
      freedom from recurrence rates, compared using an intention-to-treat analysis.
      RESULTS: : On April 5, 2010, 587 eligible patients were followed for a median of
      5.2 years (range, 1 week-11.4 years) with 5-year confirmed follow-up data for
      survival and recurrence on 567 (96.6%). Significant differences between the 2
      trial groups were as follows: LCR patients were older at randomization, and their
      pathology specimens showed smaller distal resection margins; OCR patients had
      some worse pathology parameters, but there were no differences in disease stages.
      There were no significant differences between the LCR and OCR groups in 5-year
      follow-up of overall survival (77.7% vs 76.0%, P = 0.64), recurrence-free
      survival (72.7% vs 71.2%, P = 0.70), or freedom from recurrence (86.2% vs 85.6%,
      P = 0.85). CONCLUSIONS: : In spite of some differences in short-term surrogate
      oncological markers, LCR was not inferior to OCR in direct measures of survival
      and disease recurrence. These findings emphasize the importance of long-term data
      in formulating evidence-based practice guidelines.

PMID- 23154393
TI  - Axillary dissection versus no axillary dissection in older patients with T1N0
      breast cancer: 15-year results of a randomized controlled trial.
AB  - OBJECTIVE: To assess the role of axillary dissection in older breast cancer
      patients with a clinically clear axilla. BACKGROUND: Axillary dissection, once
      standard treatment for breast cancer, is associated with considerable morbidity.
      It has been substituted by sentinel node biopsy with dissection only if the
      sentinel node is positive. We aimed to determine whether axillary surgery can be
      omitted in older women, thereby sparing them morbidity, without compromising long
      term disease control. METHODS: We carried out a randomized clinical trial on 238
      older (65-80 years) breast cancer patients, with clinically N0 disease of
      radiographic diameter 2 cm or less. Patients were randomized to quadrantectomy
      with or without axillary dissection. All received radiotherapy to the residual
      breast but not the axilla; all were prescribed tamoxifen for 5 years. Main
      outcome measures were overall survival and breast cancer mortality. We also
      assessed overt axillary disease in those who did not receive axillary dissection.
      RESULTS: After 15 years of follow-up, distant metastasis rate, overall survival,
      and breast cancer mortality in the axillary dissection and no axillary dissection
      arms were indistinguishable. The 15-year cumulative incidence of overt axillary
      disease in the no axillary dissection arm was only 6%. CONCLUSIONS: Older
      patients with early breast cancer and a clinically clear axilla treated by
      conservative surgery, postoperative radiotherapy, and adjuvant tamoxifen do not
      benefit from axillary dissection. This study was registered at clinicaltrials.gov
      (ID NCT00002720).

PMID- 23154394
TI  - Nonoperative management of rectal cancer with complete clinical response after
      neoadjuvant therapy.
AB  - INTRODUCTION: Nonoperative management (NOM) of rectal cancer after a complete
      clinical response (cCR) to neoadjuvant therapy is controversial. In this article,
      we retrospectively reviewed the outcomes of patients managed with selective NOM
      after a cCR to neoadjuvant treatment and compared these with patients who
      underwent standard rectal resection with a pathological complete response (pCR).
      METHODS: Patients completing neoadjuvant chemoradiotherapy (CRT) for stage I to
      III rectal cancer between January 2006 and August 2010 were retrospectively
      reviewed. Median follow-up was calculated in months after completion of CRT.
      RESULTS: Thirty-two patients (median follow-up 28 months) were treated by NOM
      after a cCR. Among 265 treated by CRT and rectal resection, 57 patients (22%) had
      a pCR and formed the control group (median follow-up 43 months). Factors
      associated with selective use of NOM included lower pretreatment stage, older
      age, and distal tumor location (P < 0.05). In the NOM group, 6 recurred locally
      (median 11 months, range 7-14), 3 of whom also had concurrent distant recurrence.
      All 6 local failures were controlled by salvage rectal resection with no further
      local recurrence of disease (median follow-up 17 months). In the rectal
      resection/pCR group, there were no local failures. The 2-year distant disease
      free survival (88% vs 98%, P = 0.27) and overall survival (96% vs 100%, P = 0.56)
      were similar for NOM and rectal resection/pCR groups. CONCLUSIONS: Rectal
      resection was successfully avoided in 81% of patients selected for NOM. When
      combined with salvage surgery, NOM appears to achieve similar local and distant
      disease control compared with patients with a pCR treated by rectal resection.
      Longer follow-up and prospective trials are warranted to evaluate this promising
      treatment option.

PMID- 23154395
TI  - Changes of quality of life in gastric cancer patients after curative resection: a
      longitudinal cohort study in Korea.
AB  - OBJECTIVE: Little is known about how quality of life (QOL) changes over time
      after gastrectomy. We prospectively examined changes of QOL in Korean patients
      with gastric cancer after curative resection. BACKGROUND: As early detection and
      improved treatment have led to higher survival rates and an increasing number of
      long-term survivors, the importance of QOL has increased. METHODS: Patients newly
      diagnosed with gastric cancer, who were expected to undergo curative resection,
      were studied. QOL was assessed, using the European Organization for Research and
      Treatment of Cancer QLQ-C30 and its gastric module QLQ-STO22, before and after 3
      and 12 months of gastrectomy. RESULTS: In total, 465 patients were included in
      the study, and 377 and 88 patients underwent subtotal gastrectomy and total
      gastrectomy, respectively. For most of the functional or symptom scales, the mean
      score deteriorated at 3 months and generally improved during follow-up period.
      Patients with total gastrectomy had more functional and symptomatic problems
      related to QOL than those with subtotal gastrectomy during the follow-up. For
      both groups, there were temporal, unrecovered, improved, and unchanged problems
      in QOL. Fatigue; digestive symptoms such as diarrhea, dysphagia, and eating
      restrictions; body image disturbance; and cognitive functioning were the
      representative unrecovered problems, which persisted at 12 months after surgery.
      CONCLUSIONS: Our findings show that there are various functional and symptomatic
      problems, which health care providers need to manage during the postsurgical
      period. We need to continuously address fatigue, diarrhea, dysphagia, eating
      restrictions, body image disturbance, and cognitive functioning. In addition, it
      would be necessary to inform patients about possible QOL outcomes while they are
      receiving information about surgery and signing informed consent for surgery.

PMID- 23154396
TI  - Appendicectomy is associated with increased pregnancy rate: a cohort study.
AB  - OBJECTIVE: This study was carried out to determine whether pregnancy rate is
      reduced after appendicitis or appendicectomy. BACKGROUND: The association between
      appendicectomy, appendicitis, and subsequent fertility is controversial. METHODS:
      A cohort study was carried out in the Medicines Monitoring database. The cohort
      of women who underwent appendicectomy and appropriate comparators were followed
      up until first pregnancy after appendicectomy date. Pathology of the appendix was
      verified manually. The association between appendicectomy, appendicitis, and
      pregnancy was determined by Cox regression models. RESULTS: The age and social
      deprivation score-matched analyses included 2935 patients who had appendicectomy
      with 5870 comparators. There were 1277 (43.5%) pregnancies in the appendicectomy
      cohort and 2319 (39.5%) in the comparator cohort during a mean follow-up of 12.4
      (standard deviation: 7.3) years. The adjusted hazard ratios (HRs) for pregnancy
      rates were 1.20 (95% confidence interval [CI]: 1.10-1.31). In an unmatched cohort
      analysis (3009 in the appendicectomy cohort and 122,912 in the comparator
      cohort), the adjusted HRs for pregnancy rates were 1.65 (95% CI: 1.55-1.75).
      Within the histologically proven appendicitis subset, the adjusted HR was 1.21
      (95% CI: 1.08-1.37) in comparison with the matched comparator cohort. In
      comparison with the group of participants who had appendicectomy for a normal
      appendix, the HRs were 0.98 (95% CI: 0.83-1.15) for mucosal and catarrhal
      appendicitis, 0.72 (95% CI: 0.64-0.82) for suppurative appendicitis, and 0.64
      (95% CI: 0.50-0.80) for gangrenous appendicitis. CONCLUSIONS: Appendicectomy and
      early appendicitis were associated with increased pregnancy rates. Young women
      with early appendicitis had better pregnancy rates than those with advanced
      appendicitis. Early referral for laparoscopy and appendicectomy is advocated.

PMID- 23154397
TI  - Association between cholecystectomy and intestinal cancer: a national record
      linkage study.
AB  - OBJECTIVE: To investigate the risk of intestinal cancer in a cohort of people who
      had undergone cholecystectomy for gallstones, and in a cohort of people who had
      been hospitalized for gallbladder disease but had not undergone cholecystectomy.
      BACKGROUND: Some investigators have suggested that cholecystectomy increases the
      risk of intestinal cancer. Despite extensive study, the evidence remains
      inconclusive. If there is doubt about safety, the question arises of whether
      patients considering the operation should be told of a possible risk. It is also
      increasingly clear that there are noncausal associations between gallstones and
      intestinal cancer. METHOD: Analysis of record-linked hospital admission and
      mortality statistics for England from 1998 to 2008; calculation of ratio of rates
      of cancers in the cholecystectomy cohort and the gallbladder disease cohort
      compared with a control cohort. RESULTS: : In the first year after
      cholecystectomy, the rate ratios for cancer of the small intestine, colon, and
      rectum were significantly high at, respectively, 4.6 (95% confidence interval 3.9
      5.5), 2.0 (1.9-2.1), and 1.7 (1.6-1.9). Rates of these cancers were also
      significantly high in people with gallstones without cholecystectomy. By 8 to 10
      years after cholecystectomy, rate ratios had declined to nonsignificant levels.
      CONCLUSIONS: These cancers are associated with gallstones. The highest elevation
      of risk of cancer after cholecystectomy was at the shortest time interval after
      operation. Thereafter, the level of risk in the cholecystectomy and control
      cohorts gradually converged. The association in this study, between
      cholecystectomy and intestinal cancer, is very unlikely to be causal. Intestinal
      cancers are, on occasion, initially misdiagnosed as gallbladder disease.

PMID- 23154399
TI  - Discussion of the applicability of positive lymph node ratio as a proper N
      staging for predication the prognosis of gastric cancer after curative surgery
      plus extended lymphadenectomy.

PMID- 23154401
TI  - Laminin-211 in skeletal muscle function.
AB  - A chain is no stronger than its weakest link is an old idiom that holds true for
      muscle biology. As the name implies, skeletal muscle's main function is to move
      the bones. However, for a muscle to transmit force and withstand the stress that
      contractions give rise to, it relies on a chain of proteins attaching the
      cytoskeleton of the muscle fiber to the surrounding extracellular matrix. The
      importance of this attachment is illustrated by a large number of muscular
      dystrophies caused by interruption of the cytoskeletal-extracellular matrix
      interaction. One of the major components of the extracellular matrix is laminin,
      a heterotrimeric glycoprotein and a major constituent of the basement membrane.
      It has become increasingly apparent that laminins are involved in a multitude of
      biological functions, including cell adhesion, differentiation, proliferation,
      migration and survival. This review will focus on the importance of laminin-211
      for normal skeletal muscle function.

PMID- 23154402
TI  - Ste20-like kinase SLK, at the crossroads: a matter of life and death.
AB  - Reorganization of the cytoskeleton is necessary for apoptosis, proliferation,
      migration, development and tissue repair. However, it is well established that
      mutations or overexpression of key regulators contribute to the phenotype and
      progression of several pathologies such as cancer. For instance, c-src mutations
      and the overexpression of FAK have been implicated in the invasive and metastatic
      process, suggesting that components of the motility system may represent a new
      class of therapeutic targets. Over the last several years, we and others have
      established distinct roles for the Ste20-like kinase SLK, encompassing apoptosis,
      growth, motility and development. Here, we review the SLK field from its initial
      cloning to the most recent findings from our laboratory. We summarize the various
      roles of SLK and the biochemical mechanisms that regulate its activity. These
      various findings reveal very complex functions and pattern of regulation for SLK
      in development and cancer, making it a potential therapeutic target.

PMID- 23154403
TI  - Laminins and retinal vascular development.
AB  - The mechanisms controlling vascular development, both normal and pathological,
      are not yet fully understood. Many diseases, including cancer and diabetic
      retinopathy, involve abnormal blood vessel formation. Therefore, increasing
      knowledge of these mechanisms may help develop novel therapeutic targets. The
      identification of novel proteins or cells involved in this process would be
      particularly useful. The retina is an ideal model for studying vascular
      development because it is easy to access, particularly in rodents where this
      process occurs post-natally. Recent studies have suggested potential roles for
      laminin chains in vascular development of the retina. This review will provide an
      overview of these studies, demonstrating the importance of further research into
      the involvement of laminins in retinal blood vessel formation.

PMID- 23154405
TI  - Electrical and structural properties of antimony-doped p-type ZnO nanorods with
      self-corrugated surfaces.
AB  - We report on p-type conductivity in antimony (Sb)-doped ZnO (ZnO:Sb) nanorods
      which have self-corrugated surfaces. The p-ZnO:Sb/n-ZnO nanorod diode shows good
      rectification characteristics, confirming that a p-n homojunction is formed in
      the ZnO nanorod diode. The low-temperature photoluminescence (PL) spectra of the
      ZnO:Sb nanorods reveal that the p-type conductivity in p-ZnO:Sb is related to the
      Sb(Zn)-2V(Zn) complex acceptors. Transmission electron microscopy (TEM) analysis
      of the ZnO:Sb nanorods also shows that the p-type conductivity is attributed to
      the Sb(Zn)-2V(Zn) complex acceptors which can be easily formed near the self
      corrugated surface regions of ZnO:Sb nanorods. These results suggest that the
      Sb(Zn)-2V(Zn) complex acceptors are mainly responsible for the p-type
      conductivity in ZnO:Sb nanorods which have corrugated surfaces.

PMID- 23154404
TI  - Protein composition and biomechanical properties of in vivo-derived basement
      membranes.
AB  - Basement membranes (BMs) evolved together with the first metazoan species
      approximately 500 million years ago. Main functions of BMs are stabilizing
      epithelial cell layers and connecting different types of tissues to functional,
      multicellular organisms. Mutations of BM proteins from worms to humans are either
      embryonic lethal or result in severe diseases, including muscular dystrophy,
      blindness, deafness, kidney defects, cardio-vascular abnormalities or retinal and
      cortical malformations. In vivo-derived BMs are difficult to come by; they are
      very thin and sticky and, therefore, difficult to handle and probe. In addition,
      BMs are difficult to solubilize complicating their biochemical analysis. For
      these reasons, most of our knowledge of BM biology is based on studies of the BM
      like extracellular matrix (ECM) of mouse yolk sac tumors or from studies of the
      lens capsule, an unusually thick BM. Recently, isolation procedures for a variety
      of BMs have been described, and new techniques have been developed to directly
      analyze the protein compositions, the biomechanical properties and the biological
      functions of BMs. New findings show that native BMs consist of approximately 20
      proteins. BMs are four times thicker than previously recorded, and proteoglycans
      are mainly responsible to determine the thickness of BMs by binding large
      quantities of water to the matrix. The mechanical stiffness of BMs is similar to
      that of articular cartilage. In mice with mutation of BM proteins, the stiffness
      of BMs is often reduced. As a consequence, these BMs rupture due to mechanical
      instability explaining many of the pathological phenotypes. Finally, the
      morphology and protein composition of human BMs changes with age, thus BMs are
      dynamic in their structure, composition and biomechanical properties.

PMID- 23154406
TI  - Angiopoietin-like protein 2 sensitively responds to weight reduction induced by
      lifestyle intervention on overweight Japanese men.
AB  - OBJECTIVE: Overexpression of Angiopoietin-like protein 2 (Angptl2) in obese
      adipose tissues promotes adipose tissue inflammation and its-related metabolic
      abnormalities. In a comparative study with adiponectin, we investigated whether
      alterations in serum Angptl2 concentrations reflect the effect of lifestyle
      intervention on weight loss and improved metabolic parameters in overweight
      subjects. METHODS: A total of 154 Japanese men (age, 40.9+/-5.1 years; body mass
      index, 26.9+/-3.6 kg m(-2); abdominal circumference, 94.1+/-8.9 cm) underwent a 3
      month lifestyle intervention and underwent follow-up for 3 months thereafter.
      RESULTS: Decreased serum Angptl2 levels, but not increased serum adiponectin
      levels, were immediately apparent at the end of 3-month lifestyle intervention.
      Angptl2 levels continued to decrease for 3 months in parallel with body weight
      loss and improvement in metabolic indicators. In subjects showing ?6% weight
      reduction, markedly reduced Angptl2 levels were detected at the end of 3-month
      intervention, whereas increased adiponectin levels were detected 3 months after
      the end of intervention. Multivariate analysis revealed changes in serum Angptl2
      levels associated with changes in triglycerides (TGs), aspartate aminotransferase
      and alanine aminotransferase. In contrast, changes in serum adiponectin levels
      were associated with altered high-density lipoprotein cholesterol (HDL-C) and
      fasting plasma glucose levels. CONCLUSION: A 3-month lifestyle intervention
      promoted weight reduction and improved glucose and lipid metabolism, an effect
      maintained 3 months later. Notably, our findings indicate that decreased Angptl2
      levels are a good indicator of reduced visceral fat and metabolic improvement at
      early stages of lifestyle intervention. Thus, Angptl2 reflects adiposity and
      might be a key protein to regulate inflammation and TG metabolism, whereas
      adiponectin levels could reflect improved glucose and HDL-C metabolism.

PMID- 23154407
TI  - Vitamin D status and parathyroid hormone levels in patients with obstructive
      sleep apnea.
AB  - BACKGROUND: Vitamin D insufficiency and high levels of parathyroid hormone (PTH)
      appear to be emerging risk factors for metabolic syndrome (MS), diabetes and
      cardiovascular disease, conditions that occur frequently in patients with
      obstructive sleep apnea syndrome (OSAS). OBJECTIVES: This study examined whether
      serum concentrations of 25-hydroxyvitamin D [25(OH)D] and PTH were associated
      with the presence of MS, diabetes and hypertension among an OSAS population.
      METHODS: A total of 826 patients (635 men and 191 women) with newly diagnosed
      OSAS were studied. The occurrence of the MS was analyzed according to the
      National Cholesterol Education Program Adult Treatment Panel III clinical
      criteria. Serum levels of 25(OH)D, PTH, glucose, triglycerides, cholesterol, HDL
      cholesterol, creatinine and uric acid were determined. RESULTS: In 55.3% of the
      men and in 63.2% of the women, the serum 25(OH)D level was less than 30 ng/ml
      (insufficient status). After adjusting for age, sex and seasonality, there was a
      significant trend of decreasing odds for diabetes [odds ratio (OR) 0.55, 95%
      confidence interval (CI) 0.33-0.94, ptrend = 0.038] and MS (OR 0.34, 95% CI 0.21
      0.56, ptrend < 0.001) with increasing vitamin D levels. Higher PTH levels were
      associated with a higher prevalence of obesity (OR 2.05, 95% CI 1.06-3.09, ptrend
      < 0.001) and hypertension (OR 1.83, 95% CI 1.01-3.05, ptrend = 0.049).
      CONCLUSIONS: These data suggest an inverse association of 25(OH)D with diabetes
      and MS and a positive association of PTH with obesity and hypertension among
      patients with OSAS. Based on our observational study, the causative nature of the
      associations cannot be established. These findings require further examination in
      prospective studies including clinical trials.

PMID- 23154408
TI  - Spinal fracture in a dog with diffuse idiopathic skeletal hyperostosis.
AB  - A six-year-old, spayed female Weimaraner dog was first presented with the
      complaint of hindlimb paresis and then hindlimb paralysis two years later after
      colliding with a tree. Radiographs and computed tomography revealed spinal
      fractures at lumbar vertebrae (L)2-3 and at L4-5. In addition, the spinal column
      was affected by new bone formation along the vertebral bodies, bridging the disc
      spaces, as seen in diffuse idiopathic skeletal hyperostosis (DISH). Open
      reduction and internal fixation was achieved with standard vertebral body
      plating. This is the first report of DISH-associated spinal fractures after minor
      trauma in a dog. Surgery resulted in return of the full function after the first,
      and in improvement of neurologic function after the second incident.

PMID- 23154409
TI  - Tif1gamma is essential for the terminal differentiation of mammary alveolar
      epithelial cells and for lactation through SMAD4 inhibition.
AB  - Transforming growth factor beta (TGFbeta) is widely recognised as an important
      factor that regulates many steps of normal mammary gland (MG) development,
      including branching morphogenesis, functional differentiation and involution.
      Tif1gamma has previously been reported to temporally and spatially control
      TGFbeta signalling during early vertebrate development by exerting negative
      effects over SMAD4 availability. To evaluate the contribution of Tif1 gamma to MG
      development, we developed a Cre/LoxP system to specifically invalidate the Tif1g
      gene in mammary epithelial cells in vivo. Tif1g-null mammary gland development
      appeared to be normal and no defects were observed during the lifespan of virgin
      mice. However, a lactation defect was observed in mammary glands of Tif1g-null
      mice. We demonstrate that Tif1 gamma is essential for the terminal
      differentiation of alveolar epithelial cells at the end of pregnancy and to
      ensure lactation. Tif1 gamma appears to play a crucial role in the crosstalk
      between TGFbeta and prolactin pathways by negatively regulating both PRL receptor
      expression and STAT5 phosphorylation, thereby impairing the subsequent
      transactivation of PRL target genes. Using HC11 cells as a model, we demonstrate
      that the effects of Tif1g knockdown on lactation depend on both SMAD4 and
      TGFbeta. Interestingly, we found that the Tif1gamma expression pattern in mammary
      epithelial cells is almost symmetrically opposite to that described for TGFbeta.
      We propose that Tif1gamma contributes to the repression of TGFbeta activity
      during late pregnancy and prevents lactation by inhibiting SMAD4.

PMID- 23154410
TI  - Distinct requirements for wnt9a and irf6 in extension and integration mechanisms
      during zebrafish palate morphogenesis.
AB  - Development of the palate in vertebrates involves cranial neural crest migration,
      convergence of facial prominences and extension of the cartilaginous framework.
      Dysregulation of palatogenesis results in orofacial clefts, which represent the
      most common structural birth defects. Detailed analysis of zebrafish
      palatogenesis revealed distinct mechanisms of palatal morphogenesis: extension,
      proliferation and integration. We show that wnt9a is required for palatal
      extension, wherein the chondrocytes form a proliferative front, undergo
      morphological change and intercalate to form the ethmoid plate. Meanwhile, irf6
      is required specifically for integration of facial prominences along a V-shaped
      seam. This work presents a mechanistic analysis of palate morphogenesis in a
      clinically relevant context.

PMID- 23154411
TI  - The Drosophila WIF1 homolog Shifted maintains glypican-independent Hedgehog
      signaling and interacts with the Hedgehog co-receptors Ihog and Boi.
AB  - Hedgehog (Hh) family proteins are secreted signaling ligands whose short- and
      long-range activities transform cellular fates in multiple contexts in organisms
      ranging from metazoans to humans. In the developing Drosophila wing,
      extracellular Hh binds to cell-bound glypican heparan sulfate proteoglycans
      (HSPGs) and the secreted protein Shifted (Shf), a member of Wnt inhibitory factor
      1 (WIF1) family. The glypicans and Shf are required for long-range Hh movement
      and signaling; it has been proposed that Shf promotes long-range Hh signaling by
      reinforcing binding between Hh and the glypicans, and that much or all of
      glypican function in Hh signaling requires Shf. However, we will show here that
      Shf maintains short-range Hh signaling in the wing via a mechanism that does not
      require the presence of or binding to the Drosophila glypicans Dally and Dally
      like protein. Conversely, we demonstrate interactions between Hh and the
      glypicans that are maintained, and even strengthened, in the absence of Shf. We
      present evidence that Shf binds to the CDO/BOC family Hh co-receptors
      Interference hedgehog (Ihog) and Brother of Ihog, suggesting that Shf regulates
      short-range Hh signaling through interactions with the receptor complex. In
      support of a functional interaction between Ihog and members of the Shf/WIF1
      family, we show that Ihog can increase the Wnt-inhibitory activity of vertebrate
      WIF1; this result raises the possibility of interactions between WIF1 and
      vertebrate CDO/BOC family members.

PMID- 23154412
TI  - A Hh-driven gene network controls specification, pattern and size of the
      Drosophila simple eyes.
AB  - During development, extracellular signaling molecules interact with intracellular
      gene networks to control the specification, pattern and size of organs. One such
      signaling molecule is Hedgehog (Hh). Hh is known to act as a morphogen,
      instructing different fates depending on the distance to its source. However, how
      Hh, when signaling across a cell field, impacts organ-specific transcriptional
      networks is still poorly understood. Here, we investigate this issue during the
      development of the Drosophila ocellar complex. The development of this sensory
      structure, which is composed of three simple eyes (or ocelli) located at the
      vertices of a triangular patch of cuticle on the dorsal head, depends on Hh
      signaling and on the definition of three domains: two areas of eya and so
      expression--the prospective anterior and posterior ocelli--and the intervening
      interocellar domain. Our results highlight the role of the homeodomain
      transcription factor engrailed (en) both as a target and as a transcriptional
      repressor of hh signaling in the prospective interocellar region. Furthermore, we
      identify a requirement for the Notch pathway in the establishment of en
      maintenance in a Hh-independent manner. Therefore, hh signals transiently during
      the specification of the interocellar domain, with en being required here for hh
      signaling attenuation. Computational analysis further suggests that this network
      design confers robustness to signaling noise and constrains phenotypic variation.
      In summary, using genetics and modeling we have expanded the ocellar gene network
      to explain how the interaction between the Hh gradient and this gene network
      results in the generation of stable mutually exclusive gene expression domains.
      In addition, we discuss some general implications our model may have in some Hh
      driven gene networks.

PMID- 23154413
TI  - Genetic elevation of sphingosine 1-phosphate suppresses dystrophic muscle
      phenotypes in Drosophila.
AB  - Duchenne muscular dystrophy is a lethal genetic disease characterized by the loss
      of muscle integrity and function over time. Using Drosophila, we show that
      dystrophic muscle phenotypes can be significantly suppressed by a reduction of
      wunen, a homolog of lipid phosphate phosphatase 3, which in higher animals can
      dephosphorylate a range of phospholipids. Our suppression analyses include
      assessing the localization of Projectin protein, a titin homolog, in sarcomeres
      as well as muscle morphology and functional movement assays. We hypothesize that
      wunen-based suppression is through the elevation of the bioactive lipid
      Sphingosine 1-phosphate (S1P), which promotes cell proliferation and
      differentiation in many tissues, including muscle. We confirm the role of S1P in
      suppression by genetically altering S1P levels via reduction of S1P lyase (Sply)
      and by upregulating the serine palmitoyl-CoA transferase catalytic subunit gene
      lace, the first gene in the de novo sphingolipid biosynthetic pathway and find
      that these manipulations also reduce muscle degeneration. Furthermore, we show
      that reduction of spinster (which encodes a major facilitator family transporter,
      homologs of which in higher animals have been shown to transport S1P) can also
      suppress dystrophic muscle degeneration. Finally, administration to adult flies
      of pharmacological agents reported to elevate S1P signaling significantly
      suppresses dystrophic muscle phenotypes. Our data suggest that localized
      intracellular S1P elevation promotes the suppression of muscle wasting in flies.

PMID- 23154415
TI  - Otx2 is an intrinsic determinant of the embryonic stem cell state and is required
      for transition to a stable epiblast stem cell condition.
AB  - Mouse embryonic stem cells (ESCs) represent the naive ground state of the
      preimplantation epiblast and epiblast stem cells (EpiSCs) represent the primed
      state of the postimplantation epiblast. Studies have revealed that the ESC state
      is maintained by a dynamic mechanism characterized by cell-to-cell spontaneous
      and reversible differences in sensitivity to self-renewal and susceptibility to
      differentiation. This metastable condition ensures indefinite self-renewal and,
      at the same time, predisposes ESCs for differentiation to EpiSCs. Despite
      considerable advances, the molecular mechanism controlling the ESC state and
      pluripotency transition from ESCs to EpiSCs have not been fully elucidated. Here
      we show that Otx2, a transcription factor essential for brain development, plays
      a crucial role in ESCs and EpiSCs. Otx2 is required to maintain the ESC
      metastable state by antagonizing ground state pluripotency and promoting
      commitment to differentiation. Furthermore, Otx2 is required for ESC transition
      into EpiSCs and, subsequently, to stabilize the EpiSC state by suppressing, in
      pluripotent cells, the mesendoderm-to-neural fate switch in cooperation with BMP4
      and Fgf2. However, according to its central role in neural development and
      differentiation, Otx2 is crucially required for the specification of ESC-derived
      neural precursors fated to generate telencephalic and mesencephalic neurons. We
      propose that Otx2 is a novel intrinsic determinant controlling the functional
      integrity of ESCs and EpiSCs.

PMID- 23154414
TI  - MicroRNAs downregulate Bag of marbles to ensure proper terminal differentiation
      in the Drosophila male germline.
AB  - In many adult stem cell lineages, the continuous production of functional
      differentiated cells depends on the maintenance of progenitor cells in an
      undifferentiated and proliferative state, as well as the subsequent commitment to
      proper terminal differentiation. In the Drosophila male germline stem cell (GSC)
      lineage, a key differentiation factor, Bag of marbles (Bam), is required for the
      transition from proliferative spermatogonia to differentiating spermatocytes. We
      show that bam mRNA, but not Bam, is present in spermatocytes, suggesting that bam
      is regulated post-transcriptionally. Consistent with this, repression of Bam
      accumulation is achieved by microRNAs via the bam 3'UTR. When the bam 3'UTR was
      substituted with the 3'UTR of a constitutively expressed alpha-Tubulin, Bam
      became stabilized in spermatocytes. Moreover, such a persistent expression of Bam
      in spermatocytes was recapitulated by specifically mutating the putative miR
      275/miR-306 recognition site at the bam 3'UTR. In addition, overexpression of miR
      275 or miR-306 in spermatogonial cells resulted in a delay of the proliferation
      to-differentiation transition and resembled the bam loss-of-function phenotype,
      suggesting that these microRNAs are sufficient to downregulate Bam. Finally, the
      failure of Bam downregulation in spermatocytes affected spermatid terminal
      differentiation and resulted in increased male sterility. Our results demonstrate
      that microRNAs control the stem cell differentiation pathway through regulating
      Bam, the downregulation of which is crucial for proper spermatid terminal
      differentiation.

PMID- 23154416
TI  - Protein tyrosine phosphatase 1B restrains mammary alveologenesis and secretory
      differentiation.
AB  - Tyrosine phosphorylation plays a fundamental role in mammary gland development.
      However, the role of specific tyrosine phosphatases in controlling mammary cell
      fate remains ill defined. We have identified protein tyrosine phosphatase 1B
      (PTP1B) as an essential regulator of alveologenesis and lactogenesis. PTP1B
      depletion increased the number of luminal mammary progenitors in nulliparous
      mice, leading to enhanced alveoli formation upon pregnancy. Mechanistically,
      Ptp1b deletion enhanced the expression of progesterone receptor and
      phosphorylation of Stat5, two key regulators of alveologenesis. Furthermore,
      glands from Ptp1b knockout mice exhibited increased expression of milk proteins
      during pregnancy due to enhanced Stat5 activation. These findings reveal that
      PTP1B constrains the number of mammary progenitors and thus prevents
      inappropriate onset of alveologenesis in early pregnancy. Moreover, PTP1B
      restrains the expression of milk proteins during pregnancy and thus prevents
      premature lactogenesis. Our work has implications for breast tumorigenesis
      because Ptp1b deletion has been shown to prevent or delay the onset of mammary
      tumors.

PMID- 23154417
TI  - The catalytic subunit of Arabidopsis DNA polymerase alpha ensures stable
      maintenance of histone modification.
AB  - Mitotic inheritance of identical cellular memory is crucial for development in
      multicellular organisms. The cell type-specific epigenetic state should be
      correctly duplicated upon DNA replication to maintain cellular memory during
      tissue and organ development. Although a role of DNA replication machinery in
      maintenance of epigenetic memory has been proposed, technical limitations have
      prevented characterization of the process in detail. Here, we show that
      INCURVATA2 (ICU2), the catalytic subunit of DNA polymerase alpha in Arabidopsis,
      ensures the stable maintenance of repressive histone modifications. The missense
      mutant allele icu2-1 caused a defect in the mitotic maintenance of vernalization
      memory. Although neither the recruitment of CURLY LEAF (CLF), a SET-domain
      component of Polycomb Repressive Complex 2 (PRC2), nor the resultant deposition
      of the histone mark H3K27me3 required for vernalization-induced FLOWERING LOCUS C
      (FLC) repression were affected, icu2-1 mutants exhibited unstable maintenance of
      the H3K27me3 level at the FLC region, which resulted in mosaic FLC de-repression
      after vernalization. ICU2 maintains the repressive chromatin state at additional
      PRC2 targets as well as at heterochromatic retroelements. In icu2-1 mutants, the
      subsequent binding of LIKE-HETEROCHROMATIN PROTEIN 1 (LHP1), a functional homolog
      of PRC1, at PRC2 targets was also reduced. We demonstrated that ICU2 facilitates
      histone assembly in dividing cells, suggesting a possible mechanism for ICU2
      mediated epigenetic maintenance.

PMID- 23154419
TI  - Evaluation of the chondroprotective effects of glucosamine and fish collagen
      peptide on a rabbit ACLT model using serum biomarkers.
AB  - The aim of this study was to investigate the correlations of severity of
      osteoarthritis (OA) and serum biomarkers including keratan sulfate (KS),
      hyaluronic acid (HA) and chondroitin sulfate (CS) 846 epitope. We also
      investigated the effect of glucosamine and fish collagen peptide (FCP) on OA. OA
      was induced in 12 rabbits (12 weeks of age) by anterior cruciate ligament
      transection (ACLT). After the surgery, the rabbits were orally administered FCP
      (F group), glucosamine (G group) or FCP and glucosamine (FG group) for 4 weeks.
      The control group was provided water ad libitum (C group). Blood was collected
      before surgery (pre-ACLT) and before euthanasia (post-ACLT) for serum marker
      measurement. Biomarker levels were measured by using commercial kits. We
      evaluated OA severity both macroscopically and histologically. Macroscopic
      evaluation showed mildly eroded condylar surfaces in the C group. Histological
      findings were significantly different from the FG and other groups. There were no
      significant differences between each group at post-ACLT in terms of serum KS, HA
      and CS 846. Histological assessment and serum biomarker measurements performed at
      post-ACLT showed a significant correlation between HA concentration and OA
      severity. Variations in the CS 846 concentration at pre-ACLT and post-ACLT were
      significantly correlated with OA severity. Administration of glucosamine and FCP
      had chondroprotective effects in the ACLT model. Serum biomarker concentrations
      were significantly correlated with cartilage injury. Serum biomarker measurement
      would be useful for monitoring articular cartilage damage in the clinical
      setting.

PMID- 23154418
TI  - MEF2A regulates the Gtl2-Dio3 microRNA mega-cluster to modulate WNT signaling in
      skeletal muscle regeneration.
AB  - Understanding the molecular mechanisms of skeletal muscle regeneration is crucial
      to exploiting this pathway for use in tissue repair. Our data demonstrate that
      the MEF2A transcription factor plays an essential role in skeletal muscle
      regeneration in adult mice. Injured Mef2a knockout mice display widespread
      necrosis and impaired myofiber formation. MEF2A controls this process through its
      direct regulation of the largest known mammalian microRNA (miRNA) cluster, the
      Gtl2-Dio3 locus. A subset of the Gtl2-Dio3 miRNAs represses secreted Frizzled
      related proteins (sFRPs), inhibitors of WNT signaling. Consistent with these
      data, Gtl2-Dio3-encoded miRNAs are downregulated in regenerating Mef2a knockout
      muscle, resulting in upregulated sFRP expression and attenuated WNT activity.
      Furthermore, myogenic differentiation in Mef2a-deficient myoblasts is rescued by
      overexpression of miR-410 and miR-433, two miRNAs in the Gtl2-Dio3 locus that
      repress sFRP2, or by treatment with recombinant WNT3A and WNT5A. Thus, miRNA
      mediated modulation of WNT signaling by MEF2A is a requisite step for proper
      muscle regeneration, and represents an attractive pathway for enhancing
      regeneration of diseased muscle.

PMID- 23154420
TI  - Early onset of reproductive function in female rats treated with a high-fat diet.
AB  - Puberty onset in mammals is tightly coupled to the animal's nutritional and
      metabolic state. In the present study, we evaluated the effects of a high-fat
      diet on leptin and adiponectin levels, leptin mRNA expression and puberty onset
      in female rats. On day 21, female rats were divided into 2 groups, normal food
      (NF) and high-fat food (HF). The HF group showed a significantly earlier
      (P<0.001) date of vaginal opening and lower body weight (P<0.001) than the NF
      group. The rats fed the HF food had a significantly heavier uterus (P<0.05) than
      those fed the NF food, whereas the serum leptin and adiponectin levels and leptin
      mRNA expression were not significantly different between the NF and HF groups. We
      speculate that the fat-induced nutritional imbalance in young females may lead to
      neuroendocrine dysfunction during adolescence.

PMID- 23154421
TI  - ADAMTS: novel proteases expressed by activated mast cells.
AB  - Here we show that mast cells (MCs) express the metalloproteases of the A
      disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) family, and
      that ADAMTS expression is influenced by MC activation. Co-culture of MCs with
      live Gram-positive bacteria caused a profound induction of ADAMTS-9 and -6, as
      well as down-regulated expression of ADAMTS-5. Similar patterns were also seen
      after MC activation with calcium ionophore and by immunoglobulin E receptor
      crosslinking. Moreover, ADAMTS-5, -6 and -9 were all induced by activation of
      terminally differentiated murine peritoneal MCs and in a human MC line. ADAMTS-9
      up-regulation in response to immunoglobulin E receptor crosslinking was strongly
      dependent on Go6976-sensitive protein kinase C and partly dependent on nuclear
      factor of activated T cells and nuclear factor kappa-light-chain-enhancer of
      activated B cells, respectively. The expression of ADAMTS-5, -6 and -9 was
      closely linked to MC maturation, as shown by their strong induction during the
      differentiation of bone marrow precursor cells into mature MCs. ADAMTS family
      members have been shown to possess aggrecanase activity. Accordingly, MCs were
      shown to express aggrecanase activity. Finally, ADAMTS-5 protein was detected in
      MCs by immunocytochemistry. Taken together, the present study reveals ADAMTS
      expression by MCs and that MC activation regulates the expression of these
      proteases, thus implicating the ADAMTS family of proteases in MC function.

PMID- 23154423
TI  - Evaluation of [-2] proPSA and Prostate Health Index (phi) for the detection of
      prostate cancer: a systematic review and meta-analysis.
AB  - The usefulness of %[-2] proPSA and Prostate Health Index (phi) in the detection
      of prostate cancer are currently unknown. It has been suggested that these tests
      can distinguish prostate cancer from benign prostatic diseases better than PSA or
      %fPSA. We performed a systematic review and meta-analysis of the available
      scientific evidence to evaluate the clinical usefulness of %[-2] proPSA and phi.
      Relevant published papers were identified by searching computerized bibliographic
      systems. Data on sensitivity and specificity were extracted from 12 studies: 10
      studies about %[-2] proPSA (3928 patients in total, including 1762 with confirmed
      prostate cancer) and eight studies about phi (2919 patients in total, including
      1515 with confirmed prostate cancer). The sensitivity for the detection of
      prostate cancer was 90% for %[-2] proPSA and phi, while the pooled specificity
      was 32.5% (95% CI 30.6-34.5) and 31.6% (95% CI 29.2-34.0) for %[-2] proPSA and
      phi, respectively. The measurement of %[-2] proPSA improves the accuracy of
      prostate cancer detection in comparison with PSA or %fPSA, particularly in the
      group of patients with PSA between 2 MUg/L and 10 MUg/L. Similar results were
      obtained measuring phi. Using these tests, it is possible to reduce the number of
      unnecessary biopsies, maintaining a high cancer detection rate. Published results
      also showed that %[-2] proPSA and phi are related to the aggressiveness of the
      tumor.

PMID- 23154424
TI  - Association and prognostic value of serum inflammation markers in patients with
      leukoplakia and oral cavity cancer.
AB  - BACKGROUND: Oral cavity cancer ranks as the fourth leading cancer in men in
      Taiwan. The development of a serum biomarker panel for early detection and
      disease monitoring is, therefore, warranted. METHODS: Nine inflammation
      associated markers were investigated in 46 patients with leukoplakia, 151
      patients with untreated oral cavity squamous cell carcinoma (OSCC), and 111 age-
      and gender-matched healthy controls using enzyme-linked immunosorbent assay.
      During a subsequent 28-month surveillance of OSCC patients, serum samples were
      prospectively collected at predetermined intervals following the completion of
      therapy. RESULTS: Logistic regression analysis showed matrix metalloproteases
      (MMP)-2, MMP-9, C-reactive protein (CRP), transforming growth factor-beta1 (TGF
      beta1), and E-selectin having the best discrimination power between groups and
      significant elevation trends of those five markers were noted from control to
      OSCC. By combining those five markers, a 0.888 and 0.938 area under curve by ROC
      curve analysis with 67.4% and 80% overall sensitivity and fixed 90% specificity
      for leukoplakia and OSCC groups were demonstrated. In the follow-up period, 25
      OSCC patients developed recurring or secondary tumors. All examined markers had
      decreased in relapse-free patients following treatment. However, in patients with
      relapse, interleukin-6, CRP, and serum amyloid A remained at elevated levels.
      Statistical analysis showed that patients with CRP ?2 mg/L and E-selectin ?85
      ng/mL at baseline had highest probability of relapse (odds ratio=3.029, p<0.05).
      CONCLUSIONS: The results indicate that inflammation plays a crucial role in the
      pathogenesis process of OSCC. By examining the inflammation markers, physicians
      could potentially identify patients at risk of cancer transformation or relapse.

PMID- 23154425
TI  - Homocysteine and alpha-1 antitrypsin concentration in patients with subclinical
      hypercortisolemia.
AB  - PURPOSE: Glucocorticoids have particularly strong impact on the thromboembolic
      complications. A factor which increases the risk of thrombosis is
      hyperhomocysteinemia, observed in patients with hypercortisolemia.
      Proinflammatory factors also affect the haemostatic balance. There has been an
      extensive research which estimates hemostatic system in patients with Cushing's
      syndrome. Undoubtedly, much fewer publications are available on thromboembolic
      complications in patients with Subclinical Cushing's Syndrome (SCS). The purpose
      of this study was to estimate of homocysteine (HCY) and alpha-1 antitrypsin
      (alpha1ATp) concentrations in patients with SCS. MATERIALS AND METHODS: We
      studied 35 patients (56.0 +/- 15.0 years) with SCS and 33 healthy volunteers
      (53.3 +/- 17.7 years). In all subjects the analysis of HCY and alpha1ATp
      concentration in serum was determined with an immunonephelometric method. P
      values below 0.05 were considered statistically significant. RESULTS: A
      comparison of HCY and alpha1ATp mean concentrations in patients with SCS and
      healthy representatives indicated statistically higher values of both analysed
      parameters in the sera of patients than in the healthy controls (p values were
      0.018 and 0.008, respectively). In the patients with SCS a negative correlation
      between alpha1ATp and cortisol concentration in overnight dexamethasone test was
      found (p=0.017, R=-0.40). We did not reveal any statistically significant
      correlation between the concentrations of HCY and alpha1ATp, and coagulation
      parameters such as INR, APTT, fibrinogen concentration in patients with SCS.
      CONCLUSIONS: On the basis of the obtained results, a slight increase in the
      concentration of homocysteine and alpha1ATp is observed in patients with SCS,
      which may influence vascular complications.

PMID- 23154422
TI  - Mitochondrial pathways in sarcopenia of aging and disuse muscle atrophy.
AB  - Muscle loss during aging and disuse is a highly prevalent and disabling
      condition, but knowledge about cellular pathways mediating muscle atrophy is
      still limited. Given the postmitotic nature of skeletal myocytes, the maintenance
      of cellular homeostasis relies on the efficiency of cellular quality control
      mechanisms. In this scenario, alterations in mitochondrial function are
      considered a major factor underlying sarcopenia and muscle atrophy. Damaged
      mitochondria are not only less bioenergetically efficient, but also generate
      increased amounts of reactive oxygen species, interfere with cellular quality
      control mechanisms, and display a greater propensity to trigger apoptosis. Thus,
      mitochondria stand at the crossroad of signaling pathways that regulate skeletal
      myocyte function and viability. Studies on these pathways have sometimes provided
      unexpected and counterintuitive results, which suggests that they are organized
      into a complex, heterarchical network that is currently insufficiently
      understood. Untangling the complexity of such a network will likely provide
      clinicians with novel and highly effective therapeutics to counter the muscle
      loss associated with aging and disuse. In this review, we summarize the current
      knowledge on the mechanisms whereby mitochondrial dysfunction intervenes in the
      pathogenesis of sarcopenia and disuse atrophy, and highlight the prospect of
      targeting specific processes to treat these conditions.

PMID- 23154426
TI  - Cytotoxicity evaluation of three light-cured dentin adhesive materials on human
      gingival fibroblasts, ex vivo.
AB  - PURPOSE: To evaluate the cytotoxic effects of three current light-cured dentin
      adhesives, in both uncured and post-cured conditions, on human gingival
      fibroblasts. MATERIAL AND METHODS: The materials tested were Heliobond, Adper
      Single Bond 2 and Xeno V, which are characterized by various compositions and
      application procedures. Each agent, in volumes of 5 and 10 MUL, was tested after
      polymerization, and those unpolymerized were diluted in DMEM to 10-3 and 10-5.
      The cytotoxicity of the adhesives was assessed on the basis of a test of cell
      viability in a culture of human gingival fibroblasts, with the use of tetrazolic
      salt (MTT assay). RESULTS: The results showed that, among the adhesive/bonding
      systems tested, Xeno V was the least cytotoxic. There were statistically
      significant differences in cell survival between polymerized Xeno V, Adper Single
      Bond 2 and Heliobond in the amount of 5 MUL as well as between the Xeno V and
      Adper Single Bond 2 in 10-5 dilutions. The tested adhesives were more toxic in
      the polymerized form than in the dilutions. Samples of 10 MUL resulted in a lower
      survival percentage of fibroblasts compared to 5 MUL. CONCLUSION: All the tested
      adhesives demonstrated cytopathic effects towards human gingival fibroblasts, but
      varied in their cytotoxicity. This has clinical implications. Dentists should
      follow the rules of adhesive application, precisely dose them and not allow
      direct contact with the gums as, even after polymerization, adhesive agents
      exhibit potential cytotoxic activity.

PMID- 23154427
TI  - Magnetic nanoparticles as new diagnostic tools in medicine.
AB  - Magnetic iron oxide nanoparticles have raised much interest during the recent
      years due to their novel properties (superparamagnetism, high saturation field,
      blocking temperature, etc.) and potential applications in organic synthesis,
      biotechnology and finally in medicine. The medicinal applications include:
      controlled drug delivery systems (DDS), magnetic resonance imaging (MRI),
      magnetic fluid hyperthermia (MFH), macromolecules and pathogens separation,
      cancer therapy and so on. In this paper we would like to present the newest
      literature reports concerning usage of MNPs in medicinal diagnostics such as: -
      magnetic separations of DNA (immobilization, isolation, diagnosis of genetic
      disorders and detection of exogenous substances in the organisms) - magnetic
      immobilization of proteins (applications in biotechnology, medicine, and
      catalysis) - magnetic separations of pathogens (i.e. isolation of bacteria,
      detection of various pathogens) - magnetic resonance imaging (imaging contrast
      agents, lymphangiography).

PMID- 23154428
TI  - Evidence that FGFR1 loss-of-function mutations may cause variable skeletal
      malformations in patients with Kallmann syndrome.
AB  - PURPOSE: Loss-of-function mutations in FGFR1 have been identified in
      approximately 10% of the Kallmann syndrome (KS) patients. Previous reports have
      focused mainly on olfactory, reproductive, and some other features such as cleft
      lip/palate and dental agenesis. Given the ubiquitous expression of FGFR1 during
      development, other abnormal phenotypes might, however, have been overlooked in
      these patients. Here, we demonstrate skeletal phenotypic characterization of
      patients presented with KS and FGFR1 mutations. MATERIAL AND METHODS: Using the
      Sanger DNA sequencing technique a cohort of 29 KS patients was screened. RESULTS:
      Here, we report on 5 KS patients who carry FGFR1 mutations (Gly270Asp, Gly97Ser,
      Met161Thr, Ser685Phe and Ala167Ser/Ala167Ser). Three patients presented with
      skeletal abnormalities, i.e. spine (hemivertebra and butterfly vertebra) and limb
      (oligodactyly of the feet, fusion of the 4th and 5th metacarpal bones)
      malformations in two patients and one patient, respectively. The hand phenotype
      found in the patient cannot be thought of as a counter-type of the hand phenotype
      resulting from FGFR1 gain-of-function mutations. The skeletal anomalies
      identified in the 3 KS patients are close to those observed in Fgfr1 conditional
      knockout mice. CONCLUSIONS: This study demonstrates that FGFR1 loss-of-function
      mutations can be associated with skeletal abnormalities also in humans. Further
      investigations in KS patients who carry FGFR1 mutations are needed to evaluate
      the prevalence of skeletal defects in this genetic form of KS. Conversely, the
      presence of bone malformations in a KS patient should direct the geneticist
      towards a search for mutations in FGFR1.

PMID- 23154429
TI  - Intellectual functioning of childhood leukemia survivors--relation to Tau protein
      -a marker of white matter injury.
AB  - PURPOSE: Chemo- and radiotherapy used in acute lymphoblastic leukemia (ALL) can
      influence on brain functioning in the future. In a prospective study we analysed
      the cognitive functions of ALL survivors in relation to Tau protein as a marker
      of white matter injury. MATERIAL AND METHODS: Thirty-one survivors of childhood
      ALL (6.3 years after diagnosis); without the signs of CNS involvement, treated
      with chemotherapy alone, rested in first remission; underwent Intelligence tests-
      Wechsler Intelligence Scales (WISC-R, WAIS-R). Their results were analyzed in
      relation to the levels of Tau in cerebrospinal fluid (CSF) obtained during the
      treatment. RESULTS: The analysis showed that all survivors attained the average
      scores in intelligence tests. A negative correlation was found between
      methotrexate (MTX) doses and Freedom from Distractibility (FFD). Females had
      higher values of Performance Intelligence Quotient (PIQ) than males. A negative
      correlation was noted of Tau protein levels obtained from the last CSF with:
      Total and Verbal Intelligence Quotient, PIQ, Perceptual Organisation Index and
      FFD but not with Verbal Comprehension Index. CONCLUSION: Our results suggest the
      possibility of white matter injury during the treatment for ALL with chemotherapy
      alone. Elevated Tau protein level in CSF at the end of treatment might indicate
      future difficulties in neurocognitive functioning.

PMID- 23154430
TI  - Behavioral and psychological symptoms of dementia: factor analysis and
      relationship with cognitive impairment.
AB  - BACKGROUND/AIMS: Behavioral and psychological symptoms of dementia (BPSD) affect
      almost all people with dementia at some stage during the progression of disease.
      The current study aimed at replicating previous findings on BPSD clustering in
      behavioral sub-syndromes. METHODS: One hundred and sixty-six consecutive
      outpatients with dementia attending a dementia outpatient clinic were enrolled
      and evaluated with the Neuropsychiatric Inventory and the Mini Mental State
      Examination. RESULTS: BPSD were reported in 157 patients included in the final
      sample: 140 patients (89.17%) had Alzheimer's disease (AD), while 17 patients had
      frontotemporal dementia or vascular dementia. The most frequent BPSD were
      depression in the whole sample and irritability in the AD subgroup. The severity
      of cognitive impairment was predicted by two BPSD in the whole sample (apathy and
      motor disturbance) and only by nighttime behavior in the AD subgroup. Factor
      analyses identified 4 factors, accounting for about 60% of variance in the whole
      group and in the AD subgroup of patients. CONCLUSIONS: The current study
      confirmed findings of previous studies on BPSD clustering, regarding the number
      of BPSD clusters and the total variance explained. This study has some
      limitations, including the small number of non-ADs and its monocentric character.

PMID- 23154432
TI  - TLR7 contributes to the rapid progression but not to the overall fatal outcome of
      secondary pneumococcal disease following influenza A virus infection.
AB  - Increased risk for bacterial superinfections substantially contributes to the
      mortality caused by influenza A virus (IAV) epidemics. While the mechanistic
      basis for this lethal synergism is still insufficiently understood, immune
      modulation through the viral infection has been shown to be involved. Since the
      pattern-recognition receptor (PRR) toll-like receptor 7 (TLR7) is a major sensor
      for the viral genome, we studied how IAV recognition by TLR7 influences the
      development of secondary pneumococcal infection. In a mouse model of IAV, TLR7
      deficient hosts induced a potent antiviral response and showed unchanged
      survival. In secondary pneumococcal infection during acute influenza, TLR7ko mice
      showed a fatal outcome similar to wild-type (WT) hosts, despite significantly
      delayed disease progression. Also, when bacterial superinfection occurred after
      virus clearance, WT and TLR7-deficient hosts showed similar mortality, even
      though we found the phagocytic activity of alveolar macrophages isolated from IAV
      pre-infected hosts to be enhanced in TLR7ko over WT mice. Thus, we show that a
      virus-sensing PRR modulates the progression of secondary pneumococcal infection
      following IAV. However, the fatal overall outcome in WT as well as TLR7ko hosts
      suggests that processes distinct from TLR7-triggering override the contribution
      of this single PRR.

PMID- 23154431
TI  - Blockade of inhibitors of apoptosis (IAPs) in combination with tumor-targeted
      delivery of tumor necrosis factor-alpha leads to synergistic antitumor activity.
AB  - In the current study, we examined whether the combination of tumor vasculature
      targeted gene therapy with adeno-associated virus bacteriophage-tumor necrosis
      factor-alpha (AAVP-TNF-alpha) and/or the orally administered LCL161, an
      antagonist of inhibitors of apoptosis proteins (IAPs), enhanced antitumor
      efficacy without systemic toxicity. M21 human melanoma xenografts were grown
      subcutaneously in nude mice. Mice were treated according to one of four treatment
      regimens: AAVP-TNF-alpha alone (AAVP-TNF-alpha plus sodium acetate-acetic acid
      (NaAc) buffer) via tail vein injection; LCL161 alone (phosphate-buffered saline
      (PBS) plus LCL161) via oral gavage; AAVP-TNF-alpha plus LCL161; and PBS plus NaAc
      Buffer as a control group. Tumor volume, survival and toxicity were analyzed.
      AAVP trafficking and TNF-alpha production in vivo were detected on days 7 and 21
      by real-time PCR, enzyme-linked immunosorbent assay and immunofluorescence. The
      levels of apoptosis and activation of caspases were assessed on days 7 and 21 by
      TUNEL (terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling) and
      immunofluorescence assays. Our results showed that the combination of AAVP-TNF
      alpha and LCL161 significantly inhibited tumor growth and prolonged survival in
      mice with melanoma xenografts. The combination of AAVP-TNF-alpha and LCL161 was
      also significantly more effective than either agent alone, showing a synergistic
      effect without systemic toxicity.

PMID- 23154433
TI  - Metallic nanoparticles enhanced the spontaneous emission of semiconductor
      nanocrystals embedded in nanoimprinted photonic crystals.
AB  - We report on a method to enhance the light-emission efficiency of printable thin
      films of a polymer doped with luminescent (CdSe)ZnS nanocrystals via metallic
      nanoparticles and nanoimprinted photonic crystals. We experimentally show a
      strong fluorescence enhancement of nanocrystals by coupling exciton-plasmon with
      the localized surface plasmon of metallic nanoparticles. The emitted light is
      efficiently diffracted by photonic crystals structures directly imprinted in the
      nanocomposite polymer. By combining the field susceptibility technique with
      optical Bloch equations, we examine the interaction of the quantum and plasmonic
      entities at small distances.

PMID- 23154434
TI  - Changes in circulating pro-angiogenic cytokines, other than VEGF, before
      progression to sunitinib therapy in advanced renal cell carcinoma patients.
AB  - OBJECTIVES: This study included a cohort of advanced renal cell carcinoma
      patients treated with sunitinib. Since resistance to sunitinib may be mediated
      through angiogenic cytokines other than VEGF, we measured the circulating levels
      of three pro-angiogenic cytokines: basic fibroblast growth factor (bFGF),
      hepatocyte growth factor (HGF), and interleukin (IL)-6. METHODS: Cytokines were
      measured at baseline and on the first day of each treatment cycle until
      progression in 85 advanced kidney cancer patients treated with sunitinib using a
      quantitative sandwich enzyme immunoassay (ELISA) technique. RESULTS: Even though
      no statistically significant differences in the titers of the three cytokines
      were observed between baseline and the time of progression in the whole patient
      cohort, in 45.3, 46.6, and 37.3% of the patients a more than 50% increase between
      baseline and the time of progression was shown in circulating IL-6, bFGF, and
      HGF, respectively. Furthermore, this increase was more than 100% in 37.3, 44, and
      30.6% of the patients, respectively. We also demonstrated that, in these
      patients, cytokines tended to increase and to remain high immediately before
      progression. CONCLUSIONS: In a large percentage of kidney cancer patients,
      progression is preceded by a significant increase in pro-angiogenic cytokines
      other than VEGF.

PMID- 23154435
TI  - A model-based survey of physical health in community-dwelling older adults.
AB  - BACKGROUND: Having a better comprehension of older adults' physical health can
      help healthcare professionals better design program activities to maintain and
      promote the health of this population. PURPOSE: This study investigated the
      physical health of community-dwelling older adults and compared physical health
      differences among different age subgroups, gender, and exercise habits. METHODS:
      Using stratified random sampling, 384 Taiwanese community-dwelling older adults
      were recruited in this survey research. Researchers used the Health Model of
      Older Adults to measure activities of daily living (6 indicators) and physical
      status (14 indicators). Analysis of variance and independent t test analyzed the
      data. RESULTS: Most participant physical health indicators were within normal
      ranges. Exceptions included central obesity (men: 42.90%, women: 80.30%),
      abnormal blood pressure (systolic: 47.10%, diastolic: 7%), and deteriorated lung
      capacity (men: 59.30%, women: 70.70%). Young-old subgroup participants (65-74
      years old) and exercisers performed better in their activities of daily living
      and had better physical status than old-old subgroup participants (> 85 years
      old) and nonexercisers (all p < .05). Men had better physical status than women
      (all p < .05). CONCLUSIONS/IMPLICATIONS FOR PRACTICE: Maintaining an active
      lifestyle and exercising regularly are essential to delaying or preventing the
      deterioration of natural aging. Physical tolerance, functional ability,
      educational level, and gender differences should be considered when designing a
      health promotion program for this population. It is essential for national health
      policy to enhance older adult health and promote active and healthy aging.

PMID- 23154436
TI  - Predictors of sleep quality in community-dwelling older adults in Northern
      Taiwan.
AB  - BACKGROUND: Poor sleep quality may have a significant and negative impact on
      physical and mental health. Poor sleep quality also increases the risk of all
      cause mortality. Few studies have explored the sleep quality of community
      dwelling older adults in Taiwan. PURPOSE: This study examined the prevalence of
      sleep disturbance and potential factors of influence in community-dwelling older
      people in Taiwan. METHODS: We used a cross-sectional design to recruit a total of
      160 individuals 60 years of age or older from an urban area in northern Taiwan.
      All subjects completed a structured questionnaire that included demographic data,
      physical health status, a social activity/habit survey, as well as the Chinese
      versions of Barthel's index, Pittsburgh Sleep Quality Index, short form of the
      Geriatric Depression Scale, the SF-36 Health-Related Quality of Life Survey, and
      the Physical Activity Scale for the Elderly. RESULTS: Participants reported a
      rate of sleep disturbance of 41.9%. Sleep disturbance was associated with
      nocturia and dizziness, hypertension, increased use of medications such as
      antihypertensives and gastric medicines, poor self-reported functional status,
      depression, and sedentary lifestyle. Logistic regression showed nocturia,
      sedentary lifestyle, and mental component summary score as significant predictors
      of sleep disturbance. CONCLUSIONS/IMPLICATIONS FOR PRACTICE: Sleep disturbance
      should be examined within the context of an individual's physical, mental, and
      social status. Symptom management education and an active lifestyle are necessary
      to promote sleep quality in older people.

PMID- 23154437
TI  - Development of frailty indicators for the community-dwelling older adults.
AB  - BACKGROUND: Faster than anticipated increases in population, aging is making the
      issue of frailty among the elderly increasingly important. Despite general
      agreement that a frailty assessment is important for planning care for the older
      adults, a lack of consensus remains regarding the best methodology to use for
      frailty assessments. PURPOSE: The aim of this study was first to cross-examine
      results between perception of frailty and physical assessment outcomes then try
      to establish frailty indicators for elderly people in Taiwan. METHODS: This study
      used both qualitative and quantitative methods. From August to September 2010,
      researchers recruited a convenience sample of 10 community older adults from six
      different elderly centers in northern Taiwan. Qualitative in-depth interviews
      were conducted in Mandarin or Taiwanese and audiotaped. After the in-depth
      interview, researchers conducted a series of physical assessments on the
      participants. RESULTS: Ten elderly women were interviewed and assessed. The three
      themes identified by this study related to frailty perception included overall
      physical function performance, psychological health, and physiological health.
      These reflected the concept of successful aging. Participant frailty was compared
      with subjective perceptions to identify and/or check for consistency between
      qualitative and quantitative results. Although quantitative results revealed that
      participants were in fairly good health, there were many complaints about frailty
      during the qualitative interview. Better sensitive measures reflecting frailty
      changes are thus needed. CONCLUSIONS: These indicators can be considered as an
      integration of all maintained functions. We hope that results will provide better
      insights into understanding the process of frailty among the older adults.

PMID- 23154438
TI  - Nonimaging clinical assessment of impaired swallowing in community-dwelling older
      adults in Taiwan.
AB  - BACKGROUND: Impaired swallowing is common in elderly patients as well as those
      with neurological disorders and degenerative diseases. Convenient and accurate
      assessments should be available to community-dwelling older adults to diagnose
      and provide early management and care of swallowing difficulties, an important
      factor of influence on elderly life quality. PURPOSE: This study used convenient
      nonimaging methods to assess swallowing functions in community-dwelling older
      adults and estimated the prevalence of swallowing difficulties. METHODS: The
      study adopted a survey method and recruited 216 community-dwelling older adults
      over 65 years old in northern Taiwan. Researchers used tools including a
      swallowing test, questionnaire, water test, peripheral arterial pulse oximeter,
      and laryngeal S-EMG to assess participant swallowing functions and the prevalence
      of impaired swallowing. RESULTS: We found a 9.5% prevalence of impaired
      swallowing based on swallow questionnaire and water test results. Age correlated
      negatively with swallowing speed. A one-way ANOVA showed a significant difference
      in swallowing speed among the four age groups (F = 6.478, p < .00). A post hoc
      Scheffe comparison showed significant differences in swallowing time between the
      60- to 69- and 70- to 79-year-old groups and 60- to 69- and 80- to 89-year-old
      groups. Multiple regression of impaired swallowing on various independent
      variables showed a significant standardized coefficient of 0.163 for age (t =
      2.328, p = .021). Logistic regression showed a significant Wals test value for
      age (p = .007). The Kappa value was 0.307 for agreement analysis between impaired
      swallowing and SaO(2) value reduction of more than 2%. CONCLUSIONS/IMPLICATIONS
      FOR PRACTICE: Swallowing function deteriorates with age. Results of this study
      provide an assessment of the prevalence of impaired swallowing in community
      dwelling older adults in Taiwan. Results can help guide clinical nurses to
      enhance their objective assessment of impaired swallowing to improve patient
      quality of life.

PMID- 23154439
TI  - The effects of a spiritual learning program on improving spiritual health and
      clinical practice stress among nursing students.
AB  - BACKGROUND: Numerous studies have indicated an association between spirituality
      and health outcomes. However, little information is available about interventions
      that have been shown to enhance spiritual health and decrease stress. PURPOSE:
      This study examined the effects of a spiritual learning program (SLP) on nursing
      student-perceived spiritual health and clinical practice stress. METHOD: A
      convenience sample of nursing students currently enrolled at a nursing school in
      northern Taiwan were recruited to participate in this quasiexperimental study as
      participants to experimental and control groups via simple random sampling.
      Results from a spiritual health scale and a perceived clinical practice stress
      scale, together with the score for clinical nursing practice, were compared
      between the groups. Baseline data were collected from all participants. The
      experimental group participated in 8 weeks of 50-minute per week SLP, which
      included lectures, discussion, reflection, and spiritual practices. A second data
      set was collected from all participants after the intervention. A third data set
      was collected after all participants had performed 4 weeks of nursing clinical
      practice. RESULTS: Participants were all women. Average age was 19.4 years (SD =
      1.3 years). Generalized estimating equation analysis showed SLP to have a
      significant short-term effect on improving the total score for spiritual health
      (p < .01). Significantly greater improvement in clinical practice stress scores
      was also seen in the experimental group as compared with the control group (all p
      < .05). The experimental group obtained a higher score of the final clinical
      practice than the control group (t = 3.771, p < .001). CONCLUSION: The SLP may
      encourage participants to see stressors as meaningful events that are connected
      to individual life purposes. The program developed in this study may be used to
      improve spiritual health and reduce stress in nursing students' clinical
      practice. This SLP may be referenced when designing similar spirituality-related
      courses and applied to nursing student counseling.

PMID- 23154440
TI  - Qualitative assessment of a blended learning intervention in an undergraduate
      nursing course.
AB  - BACKGROUND: Nurses are experiencing new ethical issues because of global
      developments and changes in the healthcare environment. Blended learning is one
      of the various methods used to deliver meaningful learning experiences. Well
      designed, properly administered nursing ethics education is essential for nursing
      students to visualize the role of professional nurses. However, a literature
      review shows that only a few existing studies have touched on the subject of
      nursing student experiences with blended learning in a nursing ethics course.
      PURPOSE: This study examines how undergraduate nursing students respond to a
      blended learning approach in a nursing ethics course and how blended learning
      affects the learning process. METHODS: We used a qualitative research design with
      in-depth interviews. Participants included 28 female undergraduate nursing
      students who had completed the nursing ethics course. Each interview lasted 50
      100 minutes. The researcher conducted all interviews in 2009. RESULTS: The
      researcher identified six major themes and 13 subthemes from the data. The six
      themes included (a) enhancing thinking ability, (b) improving problem-solving
      skills, (c) reflecting in and on practice, (d) perceiving added workload, (e)
      encouraging active learning, and (f) identifying the value of nursing.
      Participants felt that the blended learning experience was a generally positive
      experience. CONCLUSION: Most participants appreciated the opportunity to take a
      more active role in the learning process, think about issues profoundly and
      critically, and exercise metacognitive powers in the thinking and decision-making
      process. Study findings may suggest productive ideas for fine-tuning blended
      learning models.

PMID- 23154441
TI  - Exploring the association between nurse workload and nurse-sensitive patient
      safety outcome indicators.
AB  - BACKGROUND: Nurses affect patient safety. Although studies have associated
      patient safety with nurse staffing levels, Taiwan's Department of Health does not
      yet support changing nurse workforce standards for medical institutions. PURPOSE:
      This study was designed to gain insight into the workload of nurses employed at
      medical institutions and to determine the relationship between nurse workload and
      nurse-sensitive patient safety outcome indicators. METHODS: This study adopted a
      cross-sectional quantitative method and collected data using a self-designed
      logbook. The study population comprised nurses from acute medical institutions,
      including medical centers and regional and district hospitals. One thousand five
      hundred logbooks were distributed to participants selected by random sampling
      from 21 city/county nursing associations across Taiwan. One thousand three
      hundred seventy-three questionnaires were retrieved; the 1,358 valid responses
      yielded a valid response rate of 90.5%. Nurses used the logbook to record
      individual working conditions for 2 weeks. Descriptive statistics included mean
      values, standard deviations, and percentages; inferential statistics included the
      Spearman rho correlation and odds ratios. RESULTS: Nurse overtime working hours
      were positively associated with the following nurse-sensitive patient safety
      outcome indicators: patient falls, decubitus/pressure ulcers, near errors in
      medication, medication errors, unplanned extubation, hospital-acquired pneumonia,
      and hospital-acquired urinary tract infections; risks of patient falls,
      decubitus/pressure ulcers, unplanned extubation, hospital-acquired pneumonia, and
      hospital-acquired urinary tract infections significantly increased when the
      patient-nurse ratio exceeded 7:1. CONCLUSION: Nurse workforce and nurse-sensitive
      patient outcome indicators are positively correlated. The results of this study
      will help professional nursing groups define suitable nursing workforce standards
      for medical institutions.

PMID- 23154442
TI  - Psychological distress in women who have experienced intrauterine insemination.
AB  - BACKGROUND: Despite evidence that psychological distress manifests itself in
      underreported and atypical ways, few studies have assessed these symptoms in
      women who have experienced intrauterine insemination (IUI). PURPOSE: The aim of
      this study was to examine the prevalence of psychological distress and explore
      the relationships among psychological distress, various demographic
      characteristics, and somatic symptoms in women who had received IUI treatment in
      Taiwan. METHODS: A cross-sectional study design was used in this study. The 117
      participants were recruited from a teaching hospital in northern Taiwan. The
      brief symptom rating scale (BSRS-5) was used as the measurement instrument, and
      scores of more than 5 on the BSRS-5 were used to mark the boundary between milder
      and more severe psychological distress. Demographic characteristics and somatic
      symptoms of IUI that contributed most significantly to psychological distress
      were identified from the data. RESULTS: Thirty-eight (32.5%) participants
      experienced psychological distress. Psychological distress was most common in
      participants (a) with husbands who were an only son, (b) who had taken medication
      during the previous week, (c) with an education level below college or
      university, and (d) who reported feeling faint. CONCLUSIONS/IMPLICATIONS FOR
      PRACTICE: The factors studied are important to understand psychological distress
      in women who have undergone IUI treatment.

PMID- 23154443
TI  - Effect of PGX, a novel functional fibre supplement, on subjective ratings of
      appetite in overweight and obese women consuming a 3-day structured, low-calorie
      diet.
AB  - INTRODUCTION: Dietary factors that help control perceived hunger might improve
      adherence to calorie-reduced diets. OBJECTIVES: The objective of the study was to
      investigate the effect of supplementing a three-day, low-calorie diet with
      PolyGlycopleX (PGX), a highly viscous fibre, on subjective ratings of appetite
      compared with a placebo. METHODS: In a double-blind crossover design with a 3
      week washout, 45 women (aged 38+/-9 years, body mass index 29.9+/-2.8 kg m(-2))
      were randomised to consume a 1000-kcal per day diet for 3 days, supplemented with
      5 g of PGX or placebo at each of breakfast, lunch and dinner. Subjective appetite
      was assessed using 100 mm visual analogue scales that were completed daily
      before, between and after consumption of meals. RESULTS: Thirty-five women
      completed the study. Consumption of PGX compared with placebo led to
      significantly lower mean area under the curve for hunger on day 3 (440.4 versus
      375.4; P=0.048), prospective consumption on day 3 (471.0 versus 401.8; P=0.017)
      and the overall 3-day average (468.6 versus 420.2; P=0.026). More specifically,
      on day 3 PGX significantly reduced total appetite, hunger, desire to eat and
      prospective consumption for 2.5 and 4.5 h after lunch and before dinner times,
      with hunger also being reduced 2.5 h after dinner (P<0.05). CONCLUSION: The
      results show that adding 5 g of PGX to meals during consumption of a low-calorie
      diet reduces subjective ratings of prospective consumption and increases the
      feelings of satiety, especially during afternoon and evening. This highly viscous
      polysaccharide may be a useful adjunct to weight-loss interventions involving
      significant caloric reductions.

PMID- 23154446
TI  - Thickness identification of two-dimensional materials by optical imaging.
AB  - Two-dimensional materials, e.g. graphene and molybdenum disulfide (MoS(2)), have
      attracted great interest in recent years. Identification of the thickness of two
      dimensional materials will improve our understanding of their thickness-dependent
      properties, and also help with scientific research and applications. In this
      paper, we propose to use optical imaging as a simple, quantitative and universal
      way to identify the thickness of two-dimensional materials, i.e. mechanically
      exfoliated graphene, nitrogen-doped chemical vapor deposition grown graphene,
      graphene oxide and mechanically exfoliated MoS(2). The contrast value can easily
      be obtained by reading the red (R), green (G) and blue (B) values at each pixel
      of the optical images of the sample and substrate, and this value increases
      linearly with sample thickness, in agreement with our calculation based on the
      Fresnel equation. This method is fast, easily performed and no expensive
      equipment is needed, which will be an important factor for large-scale sample
      production. The identification of the thickness of two-dimensional materials will
      greatly help in fundamental research and future applications.

PMID- 23154445
TI  - Phosphoproteomic analysis identifies insulin enhancement of discoidin domain
      receptor 2 phosphorylation.

PMID- 23154447
TI  - The effect of locked screw angulation on the biomechanical properties of the
      S.P.S. Free-Block plate.
AB  - OBJECTIVES: Among the locked internal fixators is one denominated S.P.S.
      (Synthesis Pengo System) Free-Block, which was designed with a locking ring that
      allows the screw to be locked and positioned obliquely. Due to the paucity of
      biomechanical studies on this system, the present work aimed to evaluate the
      influence of locked screw angulation on the resistance of the S.P.S. Free-Block
      plate. METHODS: Forty synthetic bone cylinders with 10 mm fracture gap were used.
      Forty seven-hole 3.5 mm stainless steel plates (two AO-like dynamic compression
      holes and five locked holes) were assembled according to the orientation of the
      locked screws: monocortical screws were positioned at 90o to the long axis of the
      cylinder (Group 1), and monocortical screws were positioned at 70o to its
      cylinder long axis (Group 2). In both groups, AO-like dynamic compression hole
      screws were positioned bicortically and neutrally. For each group, six specimens
      were tested until failure, three in bending and three in compression, to
      determine the loads for fatigue testing. Subsequently, for each group, 14
      specimens were tested for failure - seven by bending and seven in compression.
      RESULTS: No significant failure differences were observed between Groups 1 and 2
      under static-loading or fatigue test. CLINICAL SIGNIFICANCE: In a fracture gap
      model the orientation of the locked monocortical screws did not show any
      influence on the mechanical performance of the S.P.S. Free-Block to tests of
      axial compression and four-point bending.

PMID- 23154448
TI  - Poly(acrylic acid) modified lanthanide-doped GdVO4 hollow spheres for up
      conversion cell imaging, MRI and pH-dependent drug release.
AB  - In this study, multifunctional poly(acrylic acid) modified lanthanide-doped
      GdVO(4) nanocomposites [PAA@GdVO(4): Ln(3+) (Ln = Yb/Er, Yb/Ho, Yb/Tm)] were
      constructed by filling PAA hydrogel into GdVO(4) hollow spheres via photoinduced
      polymerization. The up-conversion (UC) emission colors (green, red and blue) can
      be tuned by changing the codopant compositions in the matrices. The composites
      have potential applications as bio-probes for cell imaging. Meanwhile, the hybrid
      spheres can act as T(1) contrast agents for magnetic resonance imaging (MRI)
      owing to the existence of Gd(3+) ions on the surface of composites. Due to the
      nature of PAA, DOX-loaded PAA@GdVO(4):Yb(3+)/Er(3+) system exhibits pH-dependent
      drug releasing kinetics. A lower pH offers a faster drug release rate. Such
      character makes the loaded DOX easily released at cancer cells. The cell uptake
      process of drug-loaded composites was observed by using confocal laser scanning
      microscopy (CLSM). The results indicate the potential application of the
      multifunctional composites as theragnostics (effective bimodal imaging probes and
      pH-responsive drug carriers).

PMID- 23154449
TI  - Elevated levels of endothelial cell-derived microparticles following short-term
      withdrawal of continuous positive airway pressure in patients with obstructive
      sleep apnea: data from a randomized controlled trial.
AB  - BACKGROUND: Obstructive sleep apnea has been associated with impaired endothelial
      function; however, the mechanisms underlying this association are not completely
      understood. Cell-derived microparticles may provide a link between obstructive
      sleep apnea and endothelial dysfunction. OBJECTIVES: This randomized controlled
      trial aimed to examine the effect of a 2-week withdrawal of continuous positive
      airway pressure (CPAP) therapy on levels of circulating microparticles. METHODS:
      Forty-one obstructive sleep apnea patients established on CPAP treatment were
      randomized to either CPAP withdrawal (subtherapeutic CPAP) or continuing
      therapeutic CPAP, for 2 weeks. Polysomnography was performed and circulating
      levels of microparticles were analyzed by flow cytometry at baseline and 2 weeks.
      RESULTS: CPAP withdrawal led to a recurrence of obstructive sleep apnea. Levels
      of CD62E+ endothelium-derived microparticles increased significantly in the CPAP
      withdrawal group compared to the continuing therapeutic CPAP group (median
      difference in change +32.4 per ul; 95% CI +7.3 to +64.1 per ul, p = 0.010). CPAP
      withdrawal was not associated with a statistically significant increase in
      granulocyte, leukocyte, and platelet-derived microparticles when compared with
      therapeutic CPAP. CONCLUSIONS: Short-term withdrawal of CPAP therapy leads to a
      significant increase in endothelium-derived microparticles, suggesting that
      microparticle formation may be causally linked to obstructive sleep apnea and may
      promote endothelial activation.

PMID- 23154450
TI  - Polypoid adenomas secondary to inflammatory colorectal polyps in 2 miniature
      dachshunds.
AB  - Two miniature dachshunds, a 7-year-old neutered male and an 8-year-old male,
      presented with chronic hematochezia and tenesmus. A solitary pedunculated or
      multiple diffuse colorectal polyps were identified by colonoscopy and resected by
      polypectomy. Inflammatory colorectal polyps (ICRPs) were diagnosed according to
      histopathological findings. Both cases were treated with immunosuppressive
      therapy, and the clinical signs were resolved, although the colorectal polyps
      remained to some extent. Several months after the initial diagnosis, both cases
      presented with recurrence of hematochezia and enlargement of the polyps. A second
      colonoscopic polypectomy was performed, and adenoma was diagnosed
      histopathologically in both cases. ICRPs are a nonneoplastic disease, but their
      long-term prognosis is unknown. Careful follow-up seems to be important, and
      repetitive biopsy is recommended when growth of polyps is identified in miniature
      dachshunds with ICRPs.

PMID- 23154451
TI  - A case report of spontaneous polyarthritis in cynomolgus monkeys.
AB  - Veterinary x-ray photography and examinations of synovial fluid, blood and urine
      were conducted on a Cynomolgus Monkey from China (5 years old) which exhibited
      macroscopically visible systemic joint swelling after the quarantine period. The
      presence of inflammatory cells in the synovial fluid obtained by arthrocentesis,
      high counts of neutrophils, monocytes and large unstained cells and the elevated
      serum CRP level suggested that the lesions in this animal were due to
      polyarthritis.

PMID- 23154452
TI  - Hemato-biochemical responses to packing in donkeys administered ascorbic acid
      during the harmattan season.
AB  - Experiments were performed to investigate the effect of ascorbic acid (AA) in
      reducing hemato-biochemical changes in pack donkeys during the cold-dry
      (harmattan) season. Six experimental donkeys administered orally AA (200 mg/kg)
      and six control donkeys not administered ascorbic acid were subjected to packing.
      Blood samples were collected from all donkeys for hematological and biochemical
      analyses. In the control donkeys, packed cell volume (PCV), erythrocyte count and
      hemoglobin concentration (Hb) decreased significantly (P<0.05) at the end of
      packing. In the experimental donkeys, there was no significant difference between
      the pre- and post-packing values of PCV, erythrocyte count and Hb. In the control
      donkeys, the neutrophil and neutrophil:lymphocyte ratio increased significantly
      (P<0.05) post packing, but in the experimental donkeys, the pre- and post-packing
      values were not significantly different. The eosinophil count increased
      significantly (P<0.05) in experimental and control donkeys post packing. In
      conclusion, packing exerted significant adverse effects on the hematological
      parameters ameliorated by AA administration. AA may modulate neutrophilia and
      induce a considerable alteration of erythroid markers in donkeys subjected to
      packing during the harmattan season. 

PMID- 23154453
TI  - The critical point at which post-weaning individual housing conditions affect the
      emission of 22-kHz calls in male rats.
AB  - It is known that long-term post-weaning individual housing significantly reduces
      emissions of 22-kHz calls in male rats. In this study, we assessed post-weaning
      successive changes in 22-kHz calls emitted by male rats under two different types
      of post-weaning housing conditions (individually and socially). In addition, we
      evaluated the critical point at which a significant reduction in 22-kHz calls
      could be observed in male rats housed individually after weaning. Significantly
      fewer 22-kHz calls were emitted by individually housed rats compared to socially
      housed rats at 16 weeks of age, indicating that 13 weeks after weaning may be a
      critical point for the reduction of 22-kHz calls caused by post-weaning
      individual housing.

PMID- 23154454
TI  - Residual malignant and normal plasma cells shortly after high dose melphalan and
      stem cell transplantation. Highlight of a putative therapeutic window in Multiple
      Myeloma?
AB  - Multiple Myeloma (MM) is an incurable malignant plasma cell disorder. We have
      evaluated the counts of Multiple Myeloma Cells (MMCs) and normal plasma cells (N
      PCs), seven days after high-dose melphalan (HDM) and autologous stem
      transplantation (ASCT). Two third of patients had detectable minimal residual
      disease (MRD+) (71.7 MMCs/uL) after induction treatment with dexamethasone and
      proteasome inhibitor. MMC counts were reduced by 92% (P <= .05) but not
      eradicated 7 days after HDM+ASCT. Post-HDM+ASCT MMCs were viable and bathed in a
      burst of MMC growth factors, linked with post-HDM aplasia. In one third of
      patients (MRD- patients), MMCs were not detectable after induction treatment and
      remained undetectable after HDM+ASCT. Major difference between MRD- and MRD+
      patients is that N-PC counts were increased 3 fold (P<.05) by HDM+ASCT in MRD-
      patients, but were unaffected in MRD+ patients. Possible explanation could be
      that clearance of MMCs in MRD- patients makes more niches available for N-PCs.
      Thus, MMCs are not fully eradicated shortly after HDM, are bathed in high
      concentrations of MMC growth factors in an almost desert BM, are viable in short
      term culture, which suggests providing additional therapies shortly after HDM to
      kill resistant MMCs before full repair of lesions.

PMID- 23154455
TI  - Increased pulsatility index is associated with intracranial arterial
      calcification.
AB  - BACKGROUND/AIMS: An increase in the pulsatility index (PI) has been suggested to
      reflect distal vascular resistance. The purpose of the present study was to
      investigate the association between intracranial arterial calcification and
      intracranial PIs. METHODS: Consecutive patients with acute ischemic stroke or
      transient ischemic attack were included. The PIs of both middle cerebral arteries
      (MCAs) were measured by transcranial Doppler ultrasonography. Intracranial
      carotid artery calcification (ICAC) was assessed on computed tomography
      angiography, and then compared with the mean PI of both MCAs. Patients with
      internal carotid artery steno-occlusion were excluded from this study. RESULTS: A
      total of 156 patients were finally enrolled. The prevalence of diabetes increased
      as the PI value increased (p for trends; p = 0.025). PI was correlated with ICAC
      score (r = 0.413, p < 0.001) and age (r = 0.507, p < 0.001). Multiple linear
      regression analysis indicated that aging and ICAC were independent determinants
      of the PI of MCA after adjusting for sex, systolic blood pressure, smoking, and
      the presence of diabetes. CONCLUSIONS: This study shows that an increase in PI
      was correlated with the severity of ICAC, which suggests calcification-related
      vascular resistance might have a role in the elevation of PI.

PMID- 23154456
TI  - A novel distribution of visual field test points to improve the correlation
      between structure-function measurements.
AB  - PURPOSE: To create a new visual field (VF) test grid centered at the optic disc
      (disc-centered field [DCF]) and to infer the combination of VF test points
      (structure-function field [SFF]), taken from the DCF and the conventional fovea
      centered 24-2 grid (24-2) of standard automated perimetry, which yields the
      strongest sectorial correlation between structure-function measurements of
      retinal nerve fiber layer (RNFL) thickness and VF sensitivity. METHODS: In 50
      eyes with ocular hypertension or open angle glaucoma, the DCF and 24-2 VF were
      measured with a humphrey field analyzer II (Full Threshold strategy) and RNFL
      thickness was measured with Stratus optical coherence tomography. test points
      from the DCF and 24-2 VF Were combined and divided into 12 sectors according to
      the spatial distribution of the RNFL. A novel VF for structure-function studies
      was established using the following criteria: each sector must contain at least
      one or two test points (depending on the sector's location), and the combination
      of test points which yields the strongest structure-function correlation is
      selected. RESULTS: The SFF consisted of 40 test points. The structure-function
      correlation for the SFF was compared with the standard 24-2 VF; a multiple
      comparison test for dependent groups was carried out using a percentile bootstrap
      method, which indicated that the sector correlation coefficients in the SFF were
      significantly higher than those in the 24-2 VF. CONCLUSIONS: The SFF, with fewer
      test locations, has a stronger structure-function correlation than the 24-2 VF.
      This improved correlation may help clinicians to better interpret functional
      measurements in relation to structural measurements.

PMID- 23154457
TI  - Wnt signaling promotes Muller cell proliferation and survival after injury.
AB  - PURPOSE: Muller glia respond to retinal injury by a reactive gliosis, but only
      rarely do mammalian glial cells re-enter the cell cycle and generate new neurons.
      In the nonmammalian retina, however, Muller glia act as stem/progenitor cells.
      Here, we tested the function of Wnt signaling in the postinjury retina, focusing
      on its ability to influence mammalian Muller cell dedifferentiation,
      proliferation, and neurogenesis. METHODS: A 532 nm frequency doubled neodymium
      doped yttrium aluminum garnet (ND:YAG) laser was used to create light burns on
      the retina of Axin2(LacZ/+) Wnt reporter mice. At various time points after
      injury, retinas were analyzed for evidence of Wnt signaling as well as glial cell
      response, proliferation, and apoptosis. Laser injuries also were created in
      Axin2(LacZ/LacZ) mice, and the effect of potentiated Wnt signaling on retinal
      repair was assessed. RESULTS: A subpopulation of mammalian Muller cells are Wnt
      responsive and, when Wnt signaling is increased, these cells showed enhanced
      proliferation in response to injury. In an environment of heightened Wnt
      signaling, caused by the loss of the Wnt negative regulator Axin2, Muller cells
      proliferated after injury and adopted the expression patterns of retinal
      progenitor cells (RPCs). The Wnt-responsive Muller cells also exhibited long-term
      survival and, in some cases, expressed the rod photoreceptor marker, rhodopsin.
      CONCLUSIONS: The Wnt pathway is activated by retinal injury, and prolonging the
      endogenous Wnt signal causes a subset of Muller cells to proliferate and
      dedifferentiate into RPCs. These data raised the possibility that transient
      amplification of Wnt signaling after retinal damage may unlock the latent
      regenerative capacity long speculated to reside in mammalian neural tissues.

PMID- 23154458
TI  - Capsaicin-induced corneal sensory denervation and healing impairment are reversed
      by NGF treatment.
AB  - PURPOSE: We aimed to evaluate the nerve growth factor (NGF) pathway and its
      influence on corneal healing mechanisms in normal conditions and in an animal
      model of corneal denervation induced by capsaicin. METHODS: Peripheral sensory
      damage was induced in rat pups by subcutaneous injection of capsaicin and the
      effects evaluated by hot-plate test, corneal nerve count, and tear secretion.
      Corneal damage was induced in capsaicin-treated and -untreated rats by epithelial
      scraping. Healing rate; NGF pathway (NGF, tyrosine kinase A [TrkA], p75); and the
      stem cell marker p63 were evaluated by RT-PCR, ELISA, Western blot, and
      immunohistochemistry. The effects of exogenous NGF administration as eye drop
      formulation were also tested. RESULTS: Capsaicin treatment induced a significant
      reduction of peripheral sensitivity, corneal innervation, tear secretion, and
      corneal healing rate. The ocular effects of capsaicin treatment were associated
      with an NGF pathway alteration. NGF eye drop treatment aided corneal healing
      mechanisms through a significant increase in the NGF receptors TrkA and p75, and
      in the stem cell marker p63. CONCLUSIONS: In this study, we show that an
      alteration in the NGF pathway is responsible for a delay in corneal healing in an
      animal model of sensory denervation. Moreover, we show that NGF eye drop
      administration modulates corneal innervation, epithelial cell healing, and
      corneal stem cells. These findings may trigger further research on the role of
      the NGF pathway in limbal stem cell deficiency.

PMID- 23154459
TI  - Comparative regional pupillography as a noninvasive biosensor screening method
      for diabetic retinopathy.
AB  - PURPOSE: We describe infrared regional pupillometry as an objective comparative
      assessment of midperipheral to central retinal sensitivity and to correlate with
      midperipheral retinal ischemia in diabetic subjects. METHODS: We tested 12 normal
      and 17 diabetic subjects using bilateral infrared pupillometry. The diabetic
      cohort included seven subjects without, five with mild, three with moderate, and
      two with severe non-proliferative diabetic retinopathy (NPDR). Central and
      annular stimuli of varying intensity were presented to one eye, and pupillary
      amplitude and constriction velocity were measured from both eyes. Light stimulus
      of increasing intensity was presented as 20 consecutive trials (stimulus duration
      of 300 ms with 3000 ms intervals). The ratio of central to peripheral responses
      (Q values) was calculated for each stimulus configuration. Average responses with
      respect to the stimulus strength were regressed with Gompertz sigmoid function.
      RESULTS: Control and moderate/severe NPDR cases comparison showed statistically
      significant differences in amplitude (Q(A)) and constriction velocity (Q(CV))
      (Wilcoxon rank sum test P = 0.002, respectively). Age difference for these groups
      was not statistically significant (Wilcoxon rank sum test P = 0.15). The
      comparison of control and diabetic subjects without NPDR/mild NPDR was
      statistically significant for Q(A) and Q(CV) (Wilcoxon rank sum test P = 0.0002
      and P = 0.001, respectively). Q(A) and Q(CV) differences were statistically
      significant between moderate/severe NPDR cases and subjects without or mild NPDR
      cases (Wilcoxon rank sum test P = 0.013). CONCLUSIONS: Q(A) and Q(CV) values
      correlated highly with the severity of diabetic retinopathy, but not with the
      duration of diabetes.

PMID- 23154460
TI  - Forskolin modifies retinal vascular development in Mrp4-knockout mice.
AB  - PURPOSE: Multidrug resistance protein 4 (MRP4) effluxes a wide variety of
      endogenous compounds, including cyclic adenosine monophosphate (cAMP), and is
      exclusively expressed in vascular endothelial cells (ECs) of the retina. This
      study aimed to investigate the role of MRP4 in retinal vascular development.
      METHODS: The retinal vascular phenotype of Mrp4(-/-) mice was examined by whole
      mount immunohistochemistry at P3, P6, and P14. The retinas from P6 pups that
      received an intraperitoneal injection of either solvent control or forskolin, an
      inducer of intracellular cAMP formation, at P4 and P5 were analyzed in terms of
      their vascular formation (vascular length, vascular branching, vascular density,
      and the number of tip cells), cell proliferation and apoptosis, and vessel
      stability. RESULTS: The Mrp4(-/-) mice exhibited no overt abnormalities in the
      development of the retinal vasculature, but retinal vascular development in the
      Mrp4(-/-) mice was suppressed in response to forskolin administration. There was
      a significant decrease in the vascular length, vascular branching, and vascular
      density, and inhibited tip cell formation at the vascular front. The forskolin
      treated Mrp4(-/-) mice showed an increased number of Ki67-positive and cleaved
      caspase 3-positive ECs, a significant decrease in the amount of pericyte
      coverage, and a reduced number of empty sleeves. In pups exposed to hyperoxia
      (75% oxygen) from P7 to P12, the Mrp4(-/-) mice showed a significant increase in
      the unvascularized retinal area. CONCLUSIONS: Mrp4(-/-) mice exhibited suppressed
      retinal vascular development in response to forskolin treatment. Thus, Mrp4 might
      have protective roles in retinal vascular development by regulating the
      intracellular cAMP level.

PMID- 23154461
TI  - Progressive degeneration of the retinal nerve fiber layer in patients with
      multiple sclerosis.
AB  - PURPOSE: To quantify changes in the retinal nerve fiber layer (RNFL) of patients
      with multiple sclerosis (MS) over 3 years and to evaluate whether treatment
      protects against RNFL degeneration. METHODS: Ninety-four MS patients and 50
      healthy subjects were followed-up over 3 years. All subjects underwent a complete
      ophthalmic examination, which included assessment of visual acuity (Snellen
      chart), color vision (Ishihara pseudoisochromatic plates), visual field
      examination, optical coherence tomography (OCT), and visual evoked potentials
      (VEPs). All patients were reevaluated at 12, 24, and 36 months to quantify
      changes in the RNFL. RESULTS: Changes were detected in RNFL thickness at the 36
      month follow-up. Significant decreases (P < 0.05, t-test) were observed in the
      mean, superior, inferior, and temporal RNFL thicknesses, and macular volume
      provided by OCT, and in the P100 latency of VEP of the MS group, but only in the
      mean and inferior RNFL thicknesses of the healthy control group. Greater changes
      in the superior and inferior RNFL thicknesses during follow-up were detected in
      the MS group. Differences between treatments were not detected, but untreated
      patients had higher degeneration in the mean and superior RNFL thicknesses during
      the follow-up (P = 0.040 and P = 0.19, respectively). CONCLUSIONS: Progressive
      axonal loss can be detected in the optic nerve fiber layer of MS patients.
      Analysis of the RNFL by OCT can be useful for evaluating MS progression and
      efficacy of treatment as a neuroprotective factor against axonal degeneration.

PMID- 23154462
TI  - Optimizing the information yield of 3-D OCT in glaucoma.
AB  - PURPOSE: To determine, first, which regions of 3-D optical coherence tomography
      (OCT) volumes can be segmented completely in the majority of subjects and,
      second, the relationship between analyzed area and thickness measurement test
      retest variability. METHODS: Three-dimensional OCT volumes (6 * 6 mm) centered
      around the fovea and optic nerve head (ONH) of 925 Rotterdam Study participants
      were analyzed; 44 participants were scanned twice. Volumes were segmented into 10
      layers, and we determined the area where all layers could be identified in at
      least 95% (macula) or 90% (ONH) of subjects. Macular volumes were divided in 2 *
      2, 4 * 4, 6 * 6, 8 * 8, or 68 blocks. We placed two circles around the ONH; the
      ONH had to fit into the smaller circle, and the larger circle had to fit into the
      segmentable part of the volume. The area between the circles was divided in 3 to
      12 segments. We determined the test-retest variability (coefficient of
      repeatability) of the retinal nerve fiber layer (RNFL) and ganglion cell layer
      (RGCL) thickness measurements as a function of size of blocks/segments. RESULTS:
      Eighty-two percent of the macular volume could be segmented in at least 95% of
      subjects; for the ONH, this was 65% in at least 90%. The radii of the circles
      were 1.03 and 1.84 mm. Depending on the analyzed area, median test-retest
      variability ranged from 8% to 15% for macular RNFL, 11% to 22% for macular RGCL,
      5% to 11% for the two together, and 18% to 22% for ONH RNFL. CONCLUSIONS: Test
      retest variability hampers a detailed analysis of 3-D OCT data. Combined macular
      RNFL and RGCL thickness averaged over larger areas had the best test-retest
      variability.

PMID- 23154463
TI  - Coenzyme Q10 instilled as eye drops on the cornea reaches the retina and protects
      retinal layers from apoptosis in a mouse model of kainate-induced retinal damage.
AB  - PURPOSE: To evaluate if coenzyme Q10 (CoQ10) can protect retinal ganglion cells
      (RGCs) from apoptosis and, when instilled as eye drops on the cornea, if it can
      reach the retina and exert its antiapoptotic activity in this area in a mouse
      model of kainate (KA)-induced retinal damage. METHODS: Rat primary or cultured
      RGCs were subjected to glutamate (50 MUM) or chemical hypoxia (Antimycin A, 200
      MUM) or serum withdrawal (FBS, 0.5%) in the presence or absence of CoQ10 (10
      MUM). Cell viability was evaluated by light microscopy and fluorescence-activated
      cell sorting analyses. Apoptosis was evaluated by caspase 3/7 activity and
      mitochondrion depolarization tetramethylrhodamine ethyl ester analysis. CoQ10
      transfer to the retina following its instillation as eye drops on the cornea was
      quantified by HPLC. Retinal protection by CoQ10 (10 MUM) eye drops instilled on
      the cornea was then evaluated in a mouse model of KA-induced excitotoxic retinal
      cell apoptosis by cleaved caspase 3 immunohistofluorescence, caspase 3/7 activity
      assays, and quantification of inhibition of RGC loss. RESULTS: CoQ10
      significantly increased viable cells by preventing RGC apoptosis. Furthermore,
      when topically applied as eye drops to the cornea, it reached the retina, thus
      substantially increasing local CoQ10 concentration and protecting retinal layers
      from apoptosis. CONCLUSIONS: The ability of CoQ10 eye drops to protect retinal
      cells from apoptosis in the mouse model of KA-induced retinal damage suggests
      that topical CoQ10 may be evaluated in designing therapies for treating apoptosis
      driven retinopathies.

PMID- 23154464
TI  - Transgenic or not? No simple answer! New biotechnology-based plant breeding
      techniques and the regulatory landscape.

PMID- 23154465
TI  - Repair or regenerate--how can we tip the balance?
AB  - The fourth EMBO conference on 'The Molecular and Cellular Basis of Regeneration
      and Repair', held in September 2012, brought together researchers from both the
      regeneration and wound-healing fields. The meeting spanned a wide range of
      research topics from basic science to clinical application, and a veritable
      melting pot of model organisms and approaches resulted in an excellent fourth
      conference in this series.

PMID- 23154466
TI  - Nicotinamide mononucleotide adenylyltransferase maintains active zone structure
      by stabilizing Bruchpilot.
AB  - Active zones are specialized presynaptic structures critical for
      neurotransmission. We show that a neuronal maintenance factor, nicotinamide
      mononucleotide adenylyltransferase (NMNAT), is required for maintaining active
      zone structural integrity in Drosophila by interacting with the active zone
      protein, Bruchpilot (BRP), and shielding it from activity-induced ubiquitin
      proteasome-mediated degradation. NMNAT localizes to the peri-active zone and
      interacts biochemically with BRP in an activity-dependent manner. Loss of NMNAT
      results in ubiquitination, mislocalization and aggregation of BRP, and subsequent
      active zone degeneration. We propose that, as a neuronal maintenance factor,
      NMNAT specifically maintains active zone structure by direct protein-protein
      interaction.

PMID- 23154467
TI  - Silencing of proviruses in embryonic cells: efficiency, stability and chromatin
      modifications.
AB  - Embryonic stem cells repress retroviral infection through transcriptional
      silencing of proviral DNAs. We characterized two distinct mechanisms of silencing
      in embryonic mouse cells infected by Moloney murine leukaemia virus (MLV): a
      highly efficient one targeting the proline transfer RNA primer-binding site
      (PBSpro), and a less efficient one operating independently of the PBS. Rare virus
      expressing populations were isolated, and the timing and efficiency of
      establishment of silencing were determined. Superinfection of the selected virus
      expressing cells with a second virus carrying a distinguishable reporter revealed
      that the PBSpro-directed silencing was still largely intact, whereas the PBS
      independent silencing was partially reduced. The timing and stability of
      silencing, and the associated chromatin modifications on newly established and
      endogenous proviruses were determined. The results indicate that epigenetic
      mechanisms with different specificity and efficiency are used to silence the
      exogenous retroviral sequences in embryonic cells.

PMID- 23154468
TI  - Production of phosphatidylinositol 5-phosphate via PIKfyve and MTMR3 regulates
      cell migration.
AB  - Although phosphatidylinositol 5-phosphate (PtdIns5P) is present in many cell
      types and its biogenesis is increased by diverse stimuli, its precise cellular
      function remains elusive. Here we show that PtdIns5P levels increase when cells
      are stimulated to move and we find PtdIns5P to promote cell migration in tissue
      culture and in a Drosophila in vivo model. First, class III phosphatidylinositol
      3-kinase, which produces PtdIns3P, was shown to be involved in migration of
      fibroblasts. In a cell migration screen for proteins containing PtdIns3P-binding
      motifs, we identified the phosphoinositide 5-kinase PIKfyve and the
      phosphoinositide 3-phosphatase MTMR3, which together constitute a
      phosphoinositide loop that produces PtdIns5P via PtdIns(3,5)P(2). The ability of
      PtdIns5P to stimulate cell migration was demonstrated directly with exogenous
      PtdIns5P and a PtdIns5P-producing bacterial enzyme. Thus, the identified
      phosphoinositide loop defines a new role for PtdIns5P in cell migration.

PMID- 23154469
TI  - Ocular surface temperature gradient is increased in eyes with bacterial corneal
      ulcers.
AB  - AIMS: To investigate the ocular surface temperature gradient in eyes with
      bacterial corneal ulcers. METHODS: Prospective examination of 12 eyes with
      bacterial corneal ulcers (group 1) and 12 control eyes (group 2). Infrared
      thermal imaging (Tomey TG 1000) was used to study the temperature of the ocular
      surface. The mean, minimum and maximum temperature of the ocular surface and
      temperature course over a time period of 10 s of sustained eye opening were
      evaluated. Furthermore, a correlation between the overall corneal temperature and
      the temperature at the base of the corneal ulcers was determined. RESULTS: A
      significant difference between both groups was present. Mean corneal temperature
      was 35.6 degrees C +/- 0.9 in group 1 and 34.8 degrees C +/- 0.8 in group 2 (p =
      0.033). The temperature course over 10 s of sustained eye opening was -0.6
      degrees C +/- 0.4 in group 1 and -0.3 degrees C +/- 0.2 in group 2 (p = 0.045).
      There was a close correlation between the mean temperature at the base of the
      corneal ulcer and the overall corneal temperature (r = 0.92, p < 0.001).
      CONCLUSION: Infrared thermal imaging can be used to objectively determine the
      increased ocular surface temperature in patients with bacterial corneal ulcers.
      The use of dynamic thermography may offer new options to monitor ocular surface
      alterations.

PMID- 23154471
TI  - Increased adenosine A1 receptor levels in hemianopia patients after cerebral
      injury: an application of PET using 11C-8-dicyclopropylmethyl-1-methyl-3
      propylxanthine.
AB  - PURPOSE: The aim of this study was to apply positron emission tomography (PET)
      with C-8-dicyclopropylmethyl-1-methyl-3-propylxanthine (MPDX), a radioligand for
      adenosine A1 receptor (A1R), to patients with hemianopia caused by brain injury
      to study neurorepair mechanisms in the brain. PATIENTS AND METHODS: Four patients
      with homonymous hemianopia and 15 healthy subjects were examined using PET to
      measure cerebral glucose metabolism, C-flumazenil (FMZ) binding to the central
      benzodiazepine receptor, and MPDX binding to A1R. Left and right regions of
      interest (ROIs) were selected, and semiquantitative data on the 3 kinds of PET
      examinations were obtained. The ROIs were referenced using the data for
      homologous regions in the contralateral hemisphere [ipsilateral/contralateral
      (I/C) ratio]. RESULTS: The I/C ratios for cerebral glucose metabolism and FMZ
      binding were low in the primary visual cortex (PVC) and visual association cortex
      in all the patients, whereas MPDX binding increased in the PVC in patients 1 and
      2. Patients 1 and 2 experienced improvement in their visual field after 1 year.
      However, the other 2 patients showed no changes. We observed an increase in MPDX
      binding to A1R in the injured portion of the PVC in the patients who recovered.
      CONCLUSIONS: Evaluation of A1R by MPDX-PET may be useful for predicting prognosis
      and understanding the compensatory and reorganization processes in hemianopia
      caused by organic brain damage.

PMID- 23154470
TI  - (18)F-FDG PET in the evaluation of acuity of deep vein thrombosis.
AB  - PURPOSE: F-FDG PET has been used for vascular disease, but its role in deep vein
      thrombosis (DVT) remains prospectively unexplored. PATIENTS AND METHODS: Whole
      body F-FDG PET/CT scans were performed in patients 1 to 10 weeks after onset of
      symptomatic DVT (n = 12) and in control subjects without DVT (n = 24). The
      metabolic activity (SUVmax) of thrombosed and contralateral nonthrombosed vein
      segments was determined. The sensitivity and specificity of F-FDG PET/CT for the
      diagnosis of DVT were determined by receiver operating characteristic curve
      analyses. In 2 patients with DVT, changes in the metabolic activity of thrombosed
      vein segments in serial F-FDG PET scans. RESULTS: The metabolic activity in
      thrombosed veins [SUVmax, 2.41 (0.75)] was visually appreciable and significantly
      higher than in nonthrombosed veins in either the contralateral extremity of
      patients with DVT [SUVmax, 1.09 (0.25), P = 0.007] or control subjects [1.21
      (0.22), P < 0.001]. The area under the receiver operating characteristic curve
      for SUVmax was 0.9773 (P < 0.001), indicating excellent accuracy. An SUVmax
      threshold of greater than 1.645 was 87.5% sensitive and 100% specific for DVT.
      Metabolic activity in thrombosed veins correlated significantly with time from
      DVT symptom onset (decrease in SUVmax of 0.02/d, P < 0.05). Best-fit-line
      analyses suggested that approximately 84 to 91 days after acute DVT, the maximum
      metabolic activity of thrombosed veins would return to normal levels.
      CONCLUSIONS: F-FDG PET/CT is accurate for detecting acute symptomatic, proximal
      DVT. Metabolic activity in thrombosed veins decreases with time, suggesting that
      F-FDG PET may be helpful in assessing the age of the clot.

PMID- 23154472
TI  - (18)F-FDG PET-detected synchronous primary neoplasms in the staging of esophageal
      cancer: incidence, cost, and impact on management.
AB  - PURPOSE: F-Fluorodeoxyglucose positron emission tomography (F-FDG PET) imaging is
      increasingly the standard of care in the staging of esophageal cancer.
      Synchronous neoplasms may be identified, and this study evaluated the prevalence
      of such tumors and their impact on management. METHODS: Five hundred ninety-one
      (73.6%) of 803 consecutive patients with biopsy-proven esophageal cancer
      underwent staging F-FDG PET or PET/CT scans. F-FDG-avid lesions were considered
      synchronous primary neoplasms if occurring at locations atypical for metastases
      from the known primary, a marked discordance in the F-FDG avidity from that of
      the primary tumor, and if there was no prior detection on conventional imaging.
      Additional investigations as appropriate were undertaken, and histopathological
      verification was obtained where possible to validate the suspected synchronous
      neoplasm. RESULTS: A synchronous neoplasm was suspected in 55 (9.3%) of 591
      patients, predominantly at sites in the colon (26) and head and neck (21).
      Additional investigations in 43 cases revealed malignant neoplasms in 8 (18.6%),
      premalignant in 9 (20.9%), and benign lesions in 26 (60.5%) cases. The management
      plan was altered in 8 patients, 1.4% overall. The total cost of added tests was
      $27,482.57 (&OV0556;21,024) with the decision to treat the esophageal cancer
      deferred by a mean of 10.7 days. CONCLUSION: F-FDG uptake concerning for
      synchronous neoplasms is evident in approximately 1 in 10 cases, and of these a
      minority will represent a malignant neoplasm that significantly impacts on
      treatment. The overall added costs per patient are relatively modest and the
      treatment delay within acceptable limits of clinical practice.

PMID- 23154473
TI  - Human radiation dose estimation of (11)C-CFT using whole-body PET.
AB  - PURPOSE: C-Labeled 2-beta-carbomethoxy-3-beta-(4-fluorophenyl)tropane (C-CFT) is
      a commonly used positron emission tomography (PET) tracer for dopamine
      transporters imaging. The present study estimated human radiation absorbed doses
      of C-CFT based on whole-body PET imaging in healthy subjects. METHODS: Whole-body
      PET was performed on 6 subjects after injection of 472.06 +/- 116.47 MBq of C
      CFT. 7 Frames were acquired for about 70 min in 7 segments of the body. Regions
      of interest were drawn on PET images of source organs. Residence time was
      calculated as the area under the time-activity curve. Radiation dosimetry was
      calculated from organ residence time using the medical internal radiation
      dosimetry (MIDR) method. RESULTS: The organs with the highest radiation-absorbed
      doses were the urinary bladder, followed the spleen, pancreas, kidneys, and
      stomach. The dose-limiting critical organ was the urinary bladder. The effective
      dose was 8.89E-03 mSv/MBq (22.9 mrem/mCi). Biexponential fitting of mean bladder
      activity demonstrated that 18% of activity was excreted via the urine.
      CONCLUSIONS: The potential radiation risks of C-CFT associated with in this study
      are well within accepted limits. C-CFT demonstrates a favorable radiation dose
      profile in humans and allows multiple PET examinations on the same subject per
      year.

PMID- 23154474
TI  - Comparison of (99m)Tc-MIBI SPECT/18F-FDG PET imaging and cardiac magnetic
      resonance imaging in patients with idiopathic dilated cardiomyopathy: assessment
      of cardiac function and myocardial injury.
AB  - OBJECTIVE: The aim of this study is to evaluate the agreement between myocardial
      F-FDG PET imaging and cardiac magnetic resonance imaging (cMRI) in assessing
      cardiac function and relationship of cMRI late gadolinium enhancement (cMRI-LGE)
      and myocardial perfusion/metabolism pattern in patients with idiopathic dilated
      cardiomyopathy (IDCM). METHODS: Forty-two consecutive patients diagnosed with
      IDCM were enrolled. All patients underwent Tc-MIBI SPECT, gated F-FDG PET
      imaging, and cMRI within 3-7 days. Cardiac function parameters were calculated
      using PET and cMRI. The segments analysis was performed using a 17-segment model.
      Patterns of perfusion/metabolism were classified as normal, mismatch, mild-to
      moderate match, and severe match, and cMRI-LGE was classified into 3 categories
      (non-LGE, mid-wall LGE, and transmural LGE). RESULTS: The correlation between
      gated PET and cMRI was excellent for end-diastolic volume (EDV; r = 0.948, P <
      0.001), end-systolic volume (ESV; r = 0.939, P < 0.001), and left ventricular
      ejection fraction (LVEF; r = 0.685, P < 0.001). EDV and ESV were underestimated,
      whereas LVEF was slightly overestimated by gated PET in comparison to cMRI.
      Perfusion/metabolism patterns varied in 3 different categories of non-LGE, mid
      wall LGE, and transmural LGE (chi = 14.276, P < 0.001). Also, 71.0% (44/62)
      segments with mid-wall LGE had normal perfusion/metabolism patterns, and 75.9%
      (63/83) perfusion/metabolism mismatch segments were shown as non-LGE. The
      incidence of LGE was significantly higher in segments with severe match than the
      other 3 segment groups (chi = 112.53, P < 0.001). CONCLUSION: There is an
      excellent agreement between gated PET and cMRI in assessment of cardiac function.
      LGE-cMRI is much more sensitive in detecting moderate fibrosis, while PET could
      detect more impaired but viable myocardium. Combining the 2 imaging modalities is
      useful for providing more comprehensive evaluations of myocardial injury in
      patients with IDCM.

PMID- 23154475
TI  - Potential role of FDG PET/CT imaging for assessing venous thromboembolic
      disorders.

PMID- 23154476
TI  - Tips for giving a memorable presentation, part VI: the effective use of questions
      by a speaker, and answering questions from listeners.
AB  - Previous articles in this series have focused on tips for educators and leaders
      in giving a presentation, followed by articles on composing the talk and
      PowerPoint slides. This article focuses on how a speaker can effectively use
      questions to engage the audience and answer questions from the listeners,
      including members of the media. Additional comments will be given on how to give
      a clear presentation so that many questions will not be necessary.

PMID- 23154477
TI  - Serendipitous observation of hepatic metastases on (18)F-fluoride PET in a
      patient with infiltrating ductal carcinoma of breast: correlation with contrast
      enhanced CT.
AB  - Serendipitous observation of multifocal bilobar hepatic metastases on F-fluoride
      (NaF) PET arising in the setting of infiltrating ductal carcinoma of breast is
      described in the present report. A 46-year-old female patient with infiltrating
      ductal carcinoma had an F-fluoride PET which demonstrated uptake in multiple
      skeletal metastasis and several upper abdominal lesions corresponding to liver
      metastases on contrast enhanced CT. F-NaF uptake in soft tissue metastases are
      likely to be more frequently encountered with the increasing use of F-NaF PET/CT
      in oncology.

PMID- 23154478
TI  - Presurgical lateralization of seizure focus in temporal lobe epilepsy with
      noninvasive imaging.
AB  - We retrospectively compared the seizure focus-localizing capability of interictal
      PET/CT to that of interictal magnetic resonance diffusion-weighted imaging and
      ictal SPECT in 21 patient candidate for neurosurgery with temporal lobe epilepsy
      (TLE) by assessing overall lateralizing ability of these modalities and
      concordance of findings on these studies with results of electroencephalography
      (EEG). PET/CT demonstrated the greatest lateralizing ability of any of the
      imaging modalities and had the highest concordance rate for lateralization with
      EEG, highlighting its increasing diagnostic utility in the preoperative imaging
      workup of patients with medically intractable TLE.

PMID- 23154479
TI  - Cardiac (18)F-FDG PET/CT with heparin detects infective vegetation in a patient
      with mechanical valve replacement.
AB  - We report the usefulness of F-FDG PET/CT for the detection and therapy evaluation
      of the infective vegetation. A 64-year-old man with history of aortic valve
      replacement presented with 2 months of fever without identifiable cause.
      Echocardiogram showed no inflammation vegetation or abnormality of mechanical
      valve function. FDG PET/CT with 50 IU/kg IV heparin revealed focal uptakes near
      the mechanical aortic valve. After antibiotics therapy, fever was ameliorated,
      and FDG PET/CT findings showed markedly decreased uptake of the lesions. FDG
      PET/CT is a powerful tool to detect endocarditis even in patients with no
      anatomical abnormalities.

PMID- 23154480
TI  - Combined (11)C-methionine and 18F-FDG PET imaging in a case of cerebral
      sparganosis.
AB  - A 35-year-old man presented with right lower extremity numbness and weakness. CT
      demonstrated an irregular left parietal hypoattenuation with a punctuate
      calcification. MRI revealed a T1 low signal and T2 high signal lesion with
      extensive surrounding edema. Gadolinium-enhanced MRI showed an irregular
      enhancing lesion. F-FDG and C-methionine PET both demonstrated high uptake in the
      left parietal lesion. Lesion SUV was 7.5 for F-FDG and 3.0 for C-methionine.
      Surgical pathology demonstrated cerebral sparganosis.

PMID- 23154481
TI  - "Hot" vertebra on (18)F-FDG PET scan: a case of vertebral hemangioma.
AB  - An F-FDG-PET with CT scan was performed to stage a tongue cancer, revealing the
      hypermetabolic region in the thoracic vertebra. This corresponded to a benign
      lesion seen on MRIs and CT.Although these findings suggested a vertebral
      hemangioma, "hot" vertebra in FDG-PET was atypical. The final diagnosis was
      confirmed capillary hemangioma by the scopic biopsy and this lesion was no change
      at 1 year later.Careful interpretation of metabolic (FDG-PET) and anatomic (CT
      and MRI) images should be performed to accurately characterize the foci of
      increased FDG uptake.

PMID- 23154484
TI  - Soft cutting of single-wall carbon nanotubes by low temperature ultrasonication
      in a mixture of sulfuric and nitric acids.
AB  - To decrease single-wall carbon nanotube (SWCNT) lengths to a value of 100-200 nm,
      aggressive cutting methods, accompanied by a high loss of starting material, are
      frequently used. We propose a cutting approach based on low temperature intensive
      ultrasonication in a mixture of sulfuric and nitric acids. The method is
      nondestructive with a yield close to 100%. It was applied to cut nanotubes
      produced in three different ways: gas-phase catalysis, chemical vapor deposition,
      and electric-arc-discharge methods. Raman and Fourier transform infrared
      spectroscopy were used to demonstrate that the cut carbon nanotubes have a low
      extent of sidewall degradation and their electronic properties are close to those
      of the untreated tubes. It was proposed to use the spectral position of the far
      infrared absorption peak as a simple criterion for the estimation of SWCNT length
      distribution in the samples.

PMID- 23154483
TI  - Levels of serum ceruloplasmin associate with pediatric nonalcoholic fatty liver
      disease.
AB  - OBJECTIVES: Nonalcoholic fatty liver disease (NAFLD) in adolescents and children
      is rapidly becoming one of the most common causes of chronic liver disease
      worldwide. NAFLD varies from simple fatty liver to nonalcoholic steatohepatitis
      (NASH) with possible fibrosis. Several studies suggest that oxidative stress
      plays a central role in several metabolic abnormalities and cellular damage that
      characterize NAFLD. We investigated whether transition metals and their related
      proteins were related to NAFLD symptoms and their underlying processes. METHODS:
      We measured copper, iron, ceruloplasmin (Cp) concentration and activity,
      transferrin (Tf), ferroxidase activity, and ferritin, and we calculated Tf
      saturation and Cp to Tf ratio (Cp/Tf) as an index of the activity of the
      antioxidant Cp-Tf system in 100 children with biopsy-proven NAFLD. Pediatric
      patients were grouped by nonalcoholic fatty liver disease score (NAS) >= 5 (30
      subjects) and NAS < 5 (70). RESULTS: Cp distinguished children with NAS >= 5 from
      those with NAS < 5 with an accuracy of 82%. Specifically, a receiver operator
      characteristics curve showed that a cutoff of 28.6 mg/dL separated NAS >= 5 from
      NAS < 5 with a specificity of 92% and a sensitivity of 76%. The Cp/Tf ratio, as
      well as copper concentration and Cp activity, decreased in the NAS >= 5 group,
      pointing out an imbalance in metal regulation. Either copper or Cp concentrations
      were lower in subjects having ballooning. CONCLUSIONS: Serum antioxidant capacity
      owing to Cp failure is strongly associated with NAFLD-related damage. Further
      studies are, however, required to clarify the role of Cp in NAFLD pathogenesis
      and to evaluate its potential application as diagnostic marker.

PMID- 23154485
TI  - Does the real ReN2 have the MoS2 structure?
AB  - Rhenium nitride (ReN(2)) with the hexagonal MoS(2) structure was recently
      synthesized by metathesis reaction under high pressure. Here the calculated
      elastic and thermodynamic stabilities and chemical bonding show that the MoS(2)
      phase is unstable based on first-principles calculations. Meanwhile, the MoS(2)
      type ReN(2) compound may be stabilized by nitrogen-vacancies from X-ray
      diffraction and supercell calculations. Structure searches identify a monoclinic
      C2/m phase for ReN(2), which is energetically more stable than previous
      predictions and MoS(2) structure over a wide range of pressures. Above 130 GPa, a
      tetragonal P4/mbm phase becomes favorable from enthalpy calculations. Both phases
      have superior mechanical properties, and their syntheses would have important
      applications fundamentally and technologically.

PMID- 23154486
TI  - Synovial osteochondromatosis and sclerosing osteosarcoma in a cat.
AB  - The clinical, radiographic and histological features of synovial
      osteochondromatosis in multiple joints and an unrelated sclerosing osteosarcoma
      of the left tibia in a cat are reported. Radiographic evaluation showed signs of
      several nodular radiopacities in both stifles and both shoulders. Pathologic
      transverse fractures of the left tibia and fibula were also present. A midfemoral
      amputation of the left hindlimb was performed and treatment consisted of lifelong
      administration of nonsteroidal anti-inflammatory drugs. Histological evaluation
      confirmed synovial osteochondromatosis of the left stifle and sclerosing
      osteosarcoma of the left tibia. This is the first report of a feline patient with
      bilateral synovial osteochondromatosis that describes the clinical, radiographic
      and histological aspects of this disease.

PMID- 23154487
TI  - Total syntheses of pamamycin 607 and methyl nonactate: stereoselective
      cyclisation of homoallylic alcohols that had been prepared with remote
      stereocontrol using allylstannanes.
AB  - The tin(IV) chloride mediated cyclisation of (Z)-homoallylic alcohols using
      phenylselenenyl chloride or phthalimide in the presence of a Lewis acid followed
      by reductive removal of the phenylselenenyl group was found to give 2,5-cis
      disubstituted tetrahydrofurans with excellent stereocontrol. Using this
      procedure, (2S,4S,8R,6Z)-9-benzyloxy-2-tert-butyldiphenylsilyloxy-8-methylnon-6
      en-4-ol (11), prepared stereoselectively via the tin(iv) chloride promoted
      reaction between the (R)-5-benzyloxy-4-methylpent-2-enyl(tributyl)stannane (3)
      and (S)-3-tert-butyldiphenylsilyloxybutanal (10), gave (2S,3R,6S,8S)-1-benzyloxy
      8-tert-butyldiphenylsilyloxy-3,6-epoxy-2-methylnonane (13) after deselenation.
      This tetrahydrofuran was selectively deprotected, oxidized and esterified to give
      methyl nonactate (2). Having established this synthesis of 2,5-cis-disubstituted
      tetrahydrofurans, it was applied to complete a synthesis of pamamycin 607 (1).
      (2S,3R,6S,8R)-1-Benzyloxy-8-[N-methyl-N-(toluene-4-sulfonyl)amino]-3,6-epoxy-2
      methylundecane (35) was prepared stereoselectively from (R)-3-[N-(toluene-4
      sulfonyl)-N-methylamino]hexanal (32) by reaction with the stannane 3 followed by
      cyclisation of the resulting alkenol 33 and deselenation. Following debenzylation
      and oxidation, an aldol reaction of the aldehyde 37 using the lithium enolate of
      2,6-dimethylphenyl propanoate (61) gave mainly the 2,3-anti-3,4-syn-adduct 48.
      After protection of the secondary alcohol as its tert-butyldimethylsilyl ether
      49, reduction using DIBAL-H and oxidation, the resulting aldehyde,
      (2S,3S,4R,5R,8S,10R)-3-tert-butyldimethylsilyloxy-2,4-dimethyl-5,8-epoxy-10-[N
      methyl-N-(toluene-4-sulfonyl)amino]tridecanal (62), was taken through to the bis
      tetrahydrofuran 65 by repeating the sequence of the reactions with the stannane
      3, cyclisation and deselenation. The N-(toluene-4-sulfonyl) group was then
      replaced by an N-(tert-butoxycarbonyl) group and O-debenzylation and oxidation
      gave the carboxylic acid 70 that corresponds to the C(1)-C(18) fragment of
      pamamycin 607 (1). Similar chemistry was used to prepare the C(1')-C(11')
      fragment 89 of the pamamycin, except that in this case the configuration of the
      secondary alcohol introduced by the allylstannane reaction had to be inverted
      using a Mitsunobu reaction before the cyclisation. Esterification of the
      carboxylic acid of the C(1)-C(18)-fragment 70 using the alcohol 89 of the C(1')
      C(11') fragment followed by selective deprotection, macrocyclisation, N
      deprotection and N-methylation gave pamamycin 607 (1) that was identical to a
      sample of the natural product.

PMID- 23154489
TI  - Topical dorzolamide therapy for taxane-related macular oedema.

PMID- 23154488
TI  - The effect of imatinib mesylate on the proliferation, invasive ability, and
      radiosensitivity of retinoblastoma cell lines.
AB  - PURPOSE: Our aim was to evaluate the potential effect of imatinib mesylate (IM),
      a small molecule that specifically inhibits the tyrosine quinase receptors, on
      the proliferation and invasive abilities of two human retinoblastoma (Rb) cell
      lines. Furthermore, the ability of IM to radiosensitize Rb cells was evaluated.
      The potential targets of IM (C-kit, PDGRF-alpha and -beta, and c-Abl) were also
      investigated in these cell lines. METHODS: Two human Rb cell lines (WERI-RB-1 and
      Y79) were cultured under normal growth conditions. An MTT-based proliferation
      assay and a Matrigel invasion assay were performed with and without exposure to
      10 MUM of IM. The cells were also irradiated with graded dosages of 0, 2, 4, 6,
      8, and 10 Gy with and without IM and their proliferations rates were analyzed.
      Western blot and immunocytochemical analysis of cytospins were performed to
      evaluate the expression of C-kit, PDGRF-alpha and -beta, and c-Abl. RESULTS: When
      IM was added to both cell lines a statistically significant (P<0.05) reduction in
      proliferation and invasive ability were observed. Exposure to IM also
      significantly increased the radiosensitivity of both Rb cell lines. The c-Abl
      expression was strongly positive, PDGRF-alpha and -beta expression were also
      positive but the C-kit expression was negative in both cell lines. CONCLUSIONS:
      These results indicate that Gleevec may be useful as an adjuvant treatment in Rb
      patients, specially those considered for radiation therapy.

PMID- 23154490
TI  - Cellular and subbasal nerve alterations in early stage Fuchs' endothelial corneal
      dystrophy: an in vivo confocal microscopy study.
AB  - PURPOSE: To analyze the morphology and density of corneal epithelial cells,
      keratocytes, and subbasal nerves, in patients with early stage Fuchs' endothelial
      corneal dystrophy (FECD) by in vivo confocal microscopy (IVCM). METHODS: IVCM
      (Confoscan 4, Nidek, Inc.) of the central cornea was performed in 30 corneas of
      30 patients with early stage FECD and 13 corneas of 13 normal controls. Images
      were analyzed for morphology and density of the superficial and basal epithelial
      cells, keratocyte density, endothelial cell density (ECD), as well as subbasal
      corneal nerve parameters. Central corneal thickness (CCT) was measured in all
      patients and normals by ultrasound pachymetry. RESULTS: The ECD was significantly
      lower (-45.5%, P<0.001) in FECD patients as compared with controls. Total number
      of nerves and main nerve trunks were significantly reduced (-46.3%, P<0.001; 
      39.7%, P<0.001) in patients with FECD. Posterior keratocyte density was
      significantly higher in FECD patients (P<0.001). Significant inverse correlations
      were found between CCT and total number of nerves (r=-0.69, P<0.001), CCT and
      main nerve trunks (-0.47, P=0.016), as well as CCT and total nerve length (r=
      0.62, P=0.006). Significant correlation was found between ECD and total number of
      nerves (r=0.44, P=0.012) as well as between ECD and main nerve trunks (r=0.65,
      P<0.001). CONCLUSIONS: IVCM demonstrates alterations in corneal innervation in
      patients with early stage FECD, suggesting a potential role of corneal nerves in
      the pathogenesis of FECD. Additional studies are required to investigate whether
      subbasal nerve alterations are caused by nonspecific corneal edema, from FECD
      induced decrease in ECD, or potentially leading to loss of endothelial cells.

PMID- 23154491
TI  - Proliferative diabetic retinopathy in long-term diabetic patients with and
      without clinical osteoarthritis.
AB  - OBJECTIVE: To determine whether some long-term diabetic patients with coexisting
      clinical osteoarthritis (OA) are less likely to develop diabetic retinopathy (DR)
      than other diabetic patients and whether there is a relation between the timing
      of the clinical OA onset and DR. DESIGN, SETTING, AND PARTICIPANTS: Retrospective
      case-control study of 85 osteoarthritic patients with 20 years or more diabetes
      (A/DM) control group and of 85 non-osteoarthritic diabetic patients (NoA/DM)
      matched for age, race, duration, and type of diabetes. Digital fundus photographs
      were graded for retinopathy in masked manner. RESULTS: Glycosylated hemoglobin,
      hypertension, and smoking showed no significant difference. Twelve out of 85
      patients (12.9%) in A/DM group developed proliferative diabetic retinopathy (PDR)
      whereas 79/85 (92.9%) NoA/DM patients developed PDR (P<0.001). The onset of OA
      symptoms was known in 80/85 of the A/D patients, including 47 patients with onset
      before or at the same year as DM and 33 patients with relative onset after the
      year of DM. All the 10 patients with PDR (10/33) developed OA subsequent to their
      initiation for diabetic treatment while 0/47 A/DM patients with the onset of
      osteoarthritic symptoms present before or the same year as their onset of
      diabetes developed PDR (P<0.001). CONCLUSION: Our study suggests that in long
      term DM, PDR was significantly associated with the absence of concomitant
      clinical OA. This observation was highly significant if the onset of the
      arthritis was the same year or before the onset of the diabetes.

PMID- 23154493
TI  - Response to Tatham and Brookes.

PMID- 23154492
TI  - The pathology of ocular cancer.
AB  - Primary cancers of the eye are rare. These include uveal melanoma, a tumor that
      preferentially affects the choroid of light-eyed, fair-skinned Europeans, and the
      pediatric retinal neoplasm retinoblastoma, which is slightly more common
      worldwide. Uveal melanoma kills about half of affected patients. Most succumb to
      hepatic metastases, which are unresponsive to current therapy. Factors indicative
      of poor prognosis include tumor size, ciliary body involvement, epithelioid
      cells, extraocular extension, lymphocytic and melanophagic infiltration, mitotic
      activity, vascular mimicry patterns, and most importantly, the detection of
      monosomy 3 and class 2 gene expression profile in tumor cells using special
      tests. Most retinoblastomas are caused by sporadic somatic mutations in the RB1
      gene, but about one-third arise in infants with germline mutations. The latter
      tend to develop earlier, are often bilateral and are transmissible to offspring
      as an autosomal dominant trait. Retinoblastoma displays varying degrees of
      differentiation including Homer Wright and Flexner-Wintersteiner rosettes and
      photoreceptor differentiation (fleurettes). Rosettes are more common in eyes
      enucleated from very young infants. Tumors composed entirely of fleurettes
      (retinoma/retinocytoma) are thought to be retinoblastoma precursors, and like
      retinoblastoma, harbor mutations in both copies of the RB1 gene. Retinoblastoma
      is a major cancer treatment success story in developed countries where most
      deaths are caused by secondary tumors in germline mutation carriers. High-risk
      histopathological features that are an indication for adjuvant chemotherapy
      include massive uveal invasion and retrolaminar optic nerve invasion. Eye-sparing
      therapies including brachyradiotherapy and systemic and intra-arterial
      chemotherapy have reduced the number of eyes with retinoblastoma requiring
      enucleation in recent years.

PMID- 23154494
TI  - Reply to Claoue et al.

PMID- 23154495
TI  - The effects of Helicobacter pylori infection on intraocular pressure in anterior
      uveitis.
AB  - PURPOSE: We investigated the influence of H. pylori infection on intraocular
      pressure (IOP) in anterior uveitis patients to clarify whether H. pylori
      infection is related to high IOP in anterior uveitis. METHODS: In this
      prospective study, 165 Korean anterior uveitis patients were examined. All
      patients underwent serological analysis to identify the cause of uveitis,
      including the presence of H. pylori infection by enzyme-linked immunosorbent
      assay. Serological values were compared between patients with and without high
      IOP. RESULTS: Seropositivity for H. pylori was 69.70% of patients with high IOP
      and 38.38% of patients with normal IOP (P<0.01). CONCLUSION: This study suggests
      that H. pylori infection is associated with high IOP in anterior uveitis.

PMID- 23154496
TI  - Diagnostic cellular yield is superior with full pars plana vitrectomy compared
      with core vitreous biopsy.
AB  - PURPOSE: Vitreous biopsy for the cytological assessment of suspected intraocular
      lymphoma and vitritis of uncertain aetiology is a standard investigation. The
      types of specimens generated and the diagnostic rate are variable within and
      between centres. There are many reasons for this but one observation that has not
      been considered previously is the differential distribution of cells in the
      vitreous gel. To test this possibility, five consecutive patients with suspected
      vitreous involvement by lymphoma or vitritis of uncertain aetiology underwent a
      core vitreous biopsy immediately before a planned full pars plana vitrectomy
      (PPV) and the cellularity of the two sampling techniques compared. METHODS: A
      prospective study of five consecutive patients requiring vitreous sampling to
      secure a firm diagnosis. For each of five patients, the core vitreous biopsy
      specimen was received in a universal tube and the PPV specimen was received in a
      vitreous cassette. Fluid (0.25 ml) was removed from both specimens, centrifuged
      and haematoxylin and eosin (H&E) stained slides prepared per sampling method. The
      slides were examined with a light microscope, the most cellular field selected
      and the number of cells per mm(2) counted and compared between sampling
      techniques. RESULTS: PPV specimen's, revealed a cellularity range that was 7.4 to
      78 * (average 31 *) greater than a core vitreous biopsy. In the two cases of a
      final diagnosis of intraocular lymphoma, the vitreous core biopsy was non
      diagnostic. Furthermore, the PPV specimen generated additional cellular material
      for numerous ancillary investigations to permit a secure diagnosis. CONCLUSIONS:
      The results of this differential vitreous sampling study has strengthened our
      anecdotal slit lamp clinical observations that inflammatory cells and lymphoma
      cells are concentrated more in the cortical vitreous. Therefore, vitreous cells
      have less chance to be sampled if a single core vitreous biopsy is performed.
      Indeed, the two cases of confirmed lymphoma generated a non-diagnostic core
      vitreous biopsy. In our centre, this study has lead to PPV being performed as a
      gold standard on all patients with suspected intraocular lymphoma or vitritis of
      uncertain aetiology.

PMID- 23154497
TI  - A case of arrested primary congenital glaucoma.

PMID- 23154499
TI  - Clinical characteristics of peripheral exudative hemorrhagic chorioretinopathy
      and its response to bevacizumab therapy.

PMID- 23154498
TI  - Diagnostic incisional biopsies in clinically indeterminate choroidal tumours.
AB  - Most intraocular tumours are reliably diagnosed by a careful clinical examination
      combined with one or more non-invasive diagnostic techniques. However, in a small
      percentage of tumours, typically small and clinically amelanotic, the features
      are insufficiently distinct for a confident clinical diagnosis and tissue is
      required for diagnosis. We used a 23-G vitreous cutter to access the biopsy site
      in 43 patients with clinically indeterminate tumours. After retinotomy, an
      incisional choroidal biopsy yielded a specimen of ~1 mm(3). Obtained tissue was
      routinely processed for light microscopy including an immunohistochemical panel
      of monoclonal antibodies. Adequate tissue for diagnosis was provided in 41/43
      (95%) patients. The sensitivity and specificity to detect malignant disease were
      0.97 and 1.00, respectively. The positive predictive value was 1.00.
      Complications included progression of pre-existing retinal detachment in 5/43
      (12%) patients and transient rise in intraocular pressure to >40 mm Hg in 6/43
      (14%) patients; 4 of these 6 patients had a pre-existing retinal detachment. No
      patient with a pre-operatively attached retina had a retinal detachment. We
      conclude that an incisional transretinal choroidal biopsy yields abundant
      material and may adequately confirm or exclude malignancy in patients with
      clinically indeterminate tumours. The complication rate can be minimised when
      patients with pre-existing retinal detachment are excluded from biopsy.

PMID- 23154500
TI  - 20-gauge and 23-gauge phacovitrectomy for idiopathic macular holes: comparison of
      complications and long-term outcomes.
AB  - PURPOSE: To assess and compare the complications and long-term visual and
      anatomical outcomes of 20- and 23-gauge phacovitrectomy (PVT) for idiopathic
      macular hole repair. METHODS: A retrospective, consecutive, interventional case
      series of 72 eyes with idiopathic macular holes were managed with 20-gauge PVT
      (n=36) or 23-gauge PVT (n=36). All patients underwent a posterior-chamber intra
      ocular lens implantation and internal-limiting-membrane peel with the aid of
      either trypan blue or brilliant blue G(250) dyes. RESULTS: The macular hole
      closure rate was 97% with 20-gauge PVT and 100% with 23-gauge PVT. Mean follow-up
      was 24.06 (+/-12.83) months with 20-gauge PVT and 17.47 (+/-5.79) with 23-gauge
      PVT. Mean visual acuity improvement in LogMar was 0.41 (+/-0.32) with 20-gauge
      PVT and 0.52 (+/-0.25) with 23-gauge PVT (P=0.135). The incidence of retinal
      breaks was higher with the 20-gauge PVT compared with the 23-gauge PVT, occurring
      in 13 (36.1%) and 4 (11.1%) cases, respectively (P=0.025). There were no cases of
      retinal detachment. Postoperative intraocular pressure (IOP), at day 1, was
      significantly higher with 20-gauge PVT at 24.77 (+/-12.68) mm Hg compared with
      17.20 (+/-6.95) mm Hg in 23-gauge PVT (P=0.0028). Operating times were longer in
      20-gauge PVT at 89.36 (+/-15.26) min compared with the 23-gauge PVT at 79.33 (+/
      23.82) min (P=0.04). CONCLUSION: The 20-gauge PVT compared with 23-gauge PVT for
      macular hole repair is a slightly longer procedure and was associated with an
      increased incidence of retinal breaks and short-term elevated IOP. Both
      techniques have comparable visual and anatomical outcomes, but the 23-gauge PVT
      has advantages with regard to safety profile and operating time.

PMID- 23154501
TI  - 5 years review of periocular basal cell carcinoma and proposed follow-up
      protocol.
AB  - AIM: (1) To investigate the recurrence of periocular basal cell carcinoma (BCC)
      reported as completely excised on histology. (2) To identify risks associated
      with recurrence. (3) To recommend a rational follow-up protocol. METHODS: This is
      a cohort study by case note review of consecutive patients undergoing excision of
      periocular BCC between 2000 and 2006 at University Hospitals of Leicester. All
      lesions were excised with 3 mm clinical margin and the defect reconstructed only
      after the excision margin was declared clear. RESULTS: A total of 413 episodes of
      surgical excision were recorded for 270 patients over the 7-year period of 2000
      2006. All of them have 5 years follow-up. Mean age 73.7 (+/-12.5). In all, 67%
      were nodular BCC and 45.4% located in the lower eyelid. The main outcome measure
      was the recurrence rate. None of the patients with primary nodular BCC suffered
      recurrence. The recurrence rate for primary morphoeaform BCC following complete
      excision is 3.8%. In total, 8.1% of patients had several lesions simultaneously
      whereas 7.8% patients had BCC in multiple locations subsequently (metachronous).
      Three patients who had previously recurrent BCC (rBCC) treated elsewhere or not
      using this method had orbital/lacrimal drainage system involvement requiring
      exenteration. CONCLUSION: We recommend that patients with a single, completely
      excised primary solid or nodular BCC can be discharged after one 6-monthly
      review, although they should be instructed to monitor for the development of
      further lesions. The incidence of recurrence for primary morphoeaform BCC is 3.8%
      and for rBCC is 3.6% over 5 years and these patients should stay under review for
      this period.

PMID- 23154502
TI  - Long-term evaluation of patients treated with dexamethasone intravitreal implant
      for macular edema due to retinal vein occlusion.
AB  - PURPOSE: To evaluate the long-term visual prognosis and complications of patients
      who received intravitreal Ozurdex injections for the treatment of macular edema
      (ME) due to retinal vein occlusion (RVO). METHODS: A total of 17 patients who
      received Ozurdex injections in our institution as part of the GENEVA study were
      recalled for examination. Recorded parameters included final visual acuity (VA),
      final retinal thickness by optical coherence tomography, persistence of ME, and
      the occurrence of any complications. RESULTS: Mean follow-up time was 50.5
      months. Patients with branch RVO (BRVO) had a more favorable prognosis than
      central RVO (CRVO), and their mean VA had improved significantly, whereas the
      mean VA for the patients with CRVO did not improve significantly. Retinal
      thickness had reduced significantly in the whole group and in each subgroup
      separately. Complications included 10 patients with cataract progression, 1 with
      elevated intraocular pressure, and 1 with neovascularization and vitreous
      hemorrhage. CONCLUSIONS: This is the first reported long-term evaluation of
      patients treated with Ozurdex. Our results indicate that it has favorable long
      term safety profile, and may have a beneficial effect on the visual prognosis in
      BRVO even in the absence of continuous treatment. Further research is required to
      establish the optimal retreatment schedule for Ozurdex.

PMID- 23154503
TI  - Intra-familial tests of association between familial idiopathic scoliosis and
      linked regions on 9q31.3-q34.3 and 16p12.3-q22.2.
AB  - OBJECTIVE: Custom genotyping of markers in families with familial idiopathic
      scoliosis were used to fine-map candidate regions on chromosomes 9 and 16 in
      order to identify candidate genes that contribute to this disorder and prioritize
      them for next-generation sequence analysis. METHODS: Candidate regions on 9q and
      16p-16q, previously identified as linked to familial idiopathic scoliosis in a
      study of 202 families, were genotyped with a high-density map of single
      nucleotide polymorphisms. Tests of linkage for fine-mapping and intra-familial
      tests of association, including tiled regression, were performed on scoliosis as
      both a qualitative and quantitative trait. RESULTS AND CONCLUSIONS: Nominally
      significant linkage results were found for markers in both candidate regions.
      Results from intra-familial tests of association and tiled regression
      corroborated the linkage findings and identified possible candidate genes
      suitable for follow-up with next-generation sequencing in these same families.
      Candidate genes that met our prioritization criteria included FAM129B and CERCAM
      on chromosome 9 and SYT1, GNAO1, and CDH3 on chromosome 16.

PMID- 23154504
TI  - Dietary lipid-dependent regulation of de novo lipogenesis and lipid partitioning
      by ketogenic essential amino acids in mice.
AB  - BACKGROUND: We have previously reported that dietary ketogenic amino acids (KAAs)
      modulate hepatic de novo lipogenesis (DNL) and prevent hepatic steatosis in mice.
      However, the dependence of the metabolic phenotypes generated by KAA on the type
      of dietary lipid source remains unclear. OBJECTIVE: The aim of this study was to
      assess the effect of KAA combined with different dietary lipid sources on hepatic
      DNL and tissue lipid partitioning in mice. DESIGN: We compared three different
      KAA-supplemented diets, in which a portion of the dietary protein was replaced by
      five major essential amino acids (Leu, Ile, Val, Lys and Thr) in high-fat diets
      based on palm oil (PO), high-oleic safflower oil (FO) or soy oil (SO). To compare
      the effects of these diets in C57B6 mice, the differential regulation of DNL and
      dietary lipid partitioning due to KAA was assessed using stable isotopic flux
      analysis. RESULTS: The different dietary oils showed strikingly different
      patterns of lipid partitioning and accumulation in tissues. High-PO diets
      increased both hepatic and adipose triglycerides (TG), whereas high-FO and high
      SO diets increased hepatic and adipose TG, respectively. Stable isotopic flux
      analysis revealed high rates of hepatic DNL in high-PO and high-FO diets, whereas
      it was reduced in the high-SO diet. KAA supplementation in high-PO and high-FO
      diets reduced hepatic TG by reducing the DNL of palmitate and the accumulation of
      dietary oleate. However, KAA supplementation in the high-SO diet failed to reduce
      hepatic DNL and TG. Interestingly, KAA reduced SO-induced accumulation of hepatic
      linoleate and enhanced SO-induced accumulation of dietary oleate. CONCLUSIONS:
      Overall, the reduction of hepatic TG by KAA is dependent on dietary lipid sources
      and occurs through the modulation of DNL and altered partitioning of dietary
      lipids. The current results provide further insight into the underlying
      mechanisms of hepatic lipid reduction by amino acids.

PMID- 23154505
TI  - Allelic differences in Medicago truncatula NIP/LATD mutants correlate with their
      encoded proteins' transport activities in planta.
AB  - Medicago truncatula NIP/LATD gene, required for symbiotic nitrogen fixing nodule
      and root architecture development, encodes a member of the NRT1(PTR) family that
      demonstrates high-affinity nitrate transport in Xenopus laevis oocytes. Of three
      Mtnip/latd mutant proteins, one retains high-affinity nitrate transport in
      oocytes, while the other two are nitrate-transport defective. To further examine
      the mutant proteins' transport properties, the missense Mtnip/latd alleles were
      expressed in Arabidopsis thaliana chl1-5, resistant to the herbicide chlorate
      because of a deletion spanning the nitrate transporter AtNRT1.1(CHL1) gene. Mtnip
      3 expression restored chlorate sensitivity in the Atchl1-5 mutant, similar to
      wild type MtNIP/LATD, while Mtnip-1 expression did not. The high-affinity nitrate
      transporter AtNRT2.1 gene was expressed in Mtnip-1 mutant roots; it did not
      complement, which could be caused by several factors. Together, these findings
      support the hypothesis that MtNIP/LATD may have another biochemical activity. 

PMID- 23154506
TI  - Sugar-induced endocytosis of plant 7TM-RGS proteins.
AB  - Plant cells use sugars mainly as a source or store of energy and carbon skeletons
      for anabolic reactions and for osmotic regulation. The perception of sugars and
      their responses are rather complex including the heterotrimeric G protein pathway
      and a seven-transmembrane RGS molecule. Previously, we found that endocytosis of
      the 7TM-RGS leads to sustained activation of the G protein pathway in the genetic
      model Arabidopsis. Here we show that other plants possess similar endocytosis
      systems of the 7TM-RGS proteins. A phosphorylation site essential for the
      endocytosis is well conserved in land plant 7TM-RGS proteins. In addition,
      conifer and tobacco 7TM-RGS proteins are internalized in response to sugar. These
      results indicate a universal mechanism to activate G signaling by endocytosis in
      plant cells that have 7TM-RGS proteins. 

PMID- 23154507
TI  - Sequence diversity and conservation in factors influencing succinate
      dehydrogenase flavinylation.
AB  - The mitochondrial enzyme succinate dehydrogenase (SDH) consists of four subunits,
      a flavoprotein (SDH1), an iron-sulfur (Fe-S) protein (SDH2) and two integral
      membrane subunits (SDH3/SDH4). In mammals and yeast, an assembly factor termed
      SDHAF2/SDH5 is required for accumulation of flavinylated SDH1. In Arabidopsis, we
      have recently reported the characterization of an unknown function protein with
      low sequence similarity to SDHAF2 that is needed for assembly and activity of SDH
      and also for normal root elongation. (1) In this short communication, we have
      reviewed the sequence diversity and conservation of SDHAF2 across kingdoms based
      on phylogenetic analysis. Given that flavinylation of SDH is dependent on the
      SDH1:SDHAF2 interaction, we have also discussed the conservation of the C
      terminal tail of SDH1, which is required for this interaction process. In
      combination, we provide comparative evidence for a conserved role of SDHAF2 as an
      assembly factor from animals to plants. 

PMID- 23154508
TI  - Possible function of VIPP1 in thylakoids: protection but not formation?
AB  - VIPP1 protein in photosynthetic organisms is homologous to bacterial PspA, which
      protects plasma membrane integrity upon stresses. Despite the proposed role of
      VIPP1 in thylakoid biogenesis, its precise function remains unclear. Recently,
      our in-depth analysis of Arabidopsis vipp1 mutants revealed VIPP1's involvement
      in the maintenance of chloroplast envelopes. Chloroplasts in intact vipp1 leaves
      exhibited spherical balloon-like morphology, which resulted from osmotic stress
      across envelopes. In fact, observation of VIPP1 fused to green fluorescence
      protein in vivo revealed that most VIPP1 is localized as a lattice-like macro
      complex attached along with the envelope. Because of the proposed function in
      thylakoids, we examined whether vipp1 also exhibited altered morphologies in
      thylakoids. Results show that thylakoid morphologies were detected irregularly,
      but vipp1 chloroplasts retained normal-appearing grana stacks. We infer that
      VIPP1 might influence thylakoids as well as envelopes, but that it is not
      involved directly in thylakoid membrane formation. 

PMID- 23154509
TI  - Circadian clock and PIF4-mediated external coincidence mechanism coordinately
      integrates both of the cues from seasonal changes in photoperiod and temperature
      to regulate plant growth in Arabidopsis thaliana.
AB  - In Arabidopsis thaliana, the circadian clock regulates the photoperiodic plant
      growth including the elongation of hypocotyls in a short-days (SDs)-specific
      manner. The clock-controlled PHYTOCHROME-INTERACTING FACTOR 4 (PIF4) gene
      encoding a basic helix-loop-helix (bHLH) transcription factor plays crucial roles
      in this regulation. The SDs-specific elongation of hypocotyls is best explained
      by accumulation of the active PIF4 proteins at the end of night specifically in
      SDs due to coincidence between internal (circadian clock) and external
      (photoperiod) cues. However, this external coincidence model was challenged with
      the recent finding that the elongation of hypocotyls is markedly promoted at high
      growth temperature (28C) even in long-days (LDs), implying that the model to
      explain the photoperiodic response of plant architecture appears to be
      conditional on ambient temperature. With regard to this problem, the results of
      this and previous studies showed that the model holds under a wide range of
      ambient temperature conditions (16C to 28C). We propose that the circadian clock
      and PIF4-mediated external coincidence mechanism coordinately integrates both of
      the cues from seasonal changes in photoperiod and temperature to regulate plant
      growth in natural habitats. 

PMID- 23154510
TI  - CDC48 function during TMV infection: regulation of virus movement and replication
      by degradation?
AB  - Cell-division-cycle protein 48 (CDC48) is an essential, conserved ATP-driven
      chaperone in eukaryotic cells, which functions in diverse cellular processes
      including the targeting of misfolded and aggregated proteins for degradation via
      proteasomal and aggresomal-autophagic pathways. We recently demonstrated that
      plant CDC48 localizes to and interacts with Tobacco mosaic virus (TMV) movement
      protein (MP) in ER-associated viral protein inclusions. Our data suggest that
      CDC48 participates in the clearance of these viral protein inclusions in an ER
      assisted protein degradation (ERAD)-like mechanism. As TMV MP-inclusions formed
      at late infection stages resemble aggresomes, we here propose that TMV MP enters
      both, ERAD-like and aggresomal pathways in its host cells and that CDC48
      coordinates these processes. Moreover, as viruses often exploit host pathways for
      replication and spread, we propose a model in which CDC48 functions in the
      degradation pathway of overaccumulating viral protein and also actively
      participates in the regulation of TMV replication and cell-to-cell movement.  

PMID- 23154511
TI  - News about cryptochrome photoreceptors in algae.
AB  - Cryptochromes (CRYs) are flavoproteins that are known as blue light
      photoreceptors in many organisms. Recently, genome sequences from a variety of
      algae became available. Functional characterizations of animal-like CRYs from
      Oestreococcus tauri, Chlamydomonas reinhardtii and Phaeodactylum tricornutum
      highlighted novel functions and properties. As arising from studies in fungi,
      certain algal CRYs of the "cryptochrome photolyase family" (PtCPF1, OtCPF1) have
      dual or even triple functions. They are involved in blue light perception and/or
      in the circadian clock and are able to repair DNA damages. On the other hand, the
      animal-like aCRY from C. reinhardtii is not only acting as sensory blue light-
      but also as sensory red light receptor thus expanding our current view of
      flavoproteins in general and CRYs in particular. The observed broad spectral
      response points to the neutral radical state of flavin, which is assumed to be
      the dark form in aCRY in contrast to the plant CRYs. 

PMID- 23154512
TI  - Loss of expression of the double strand break repair protein ATM is associated
      with worse prognosis in colorectal cancer and loss of Ku70 expression is
      associated with CIN.
AB  - Repair of double strand DNA breaks (DSBs) is pivotal in maintaining normal cell
      division and disruption of this system has been shown to be a key factor in
      carcinogenesis. Loss of expression of the DSB repair proteins have previously
      been shown to be associated with poorer survival in colorectal cancer. We wished
      to ascertain the relationship of altered expression of the DSB repair proteins
      gamma-H2AX (gamma-H2AX), ATM and Ku70 with biological and clinico-pathological
      features of colorectal cancer. 908 tumours from the VICTOR clinical trial of
      stage II/III colorectal cancer were analysed for expression of gamma-H2AX, ATM
      and Ku70 using immunohistochemistry. Expression levels were correlated with CIN
      and with disease-free survival, correcting for microsatellite instability,
      BRAF/KRAS mutation status, Dukes stage, chemo/radiotherapy, age, gender and
      tumour location. Down-regulated Ku70 expression was associated with chromosomal
      instability (p=0.029) in colorectal cancer. Reduced ATM expression was an
      independent marker of poor disease-free survival (HR=1.67, 95% CI 1.11-2.50,
      p=0.015). For Ku70, further studies are required to investigate the potential
      relationship of non-homologous end joining with chromosomal instability. Loss of
      ATM expression might serve as a biomarker of poor prognosis in colorectal cancer.

PMID- 23154513
TI  - Effect of ultrasound treatment on brain edema in a traumatic brain injury model
      with the weight drop method.
AB  - BACKGROUND: For the treatment of traumatic brain edema, an efficient modality has
      not yet emerged. There have been many studies to date which have reported the
      employment of low-frequency ultrasound for blood-brain barrier disruption (BBBD).
      However, the authors have observed that low-intensity ultrasound increases water
      permeability without cellular damage in cartilage cells. We have therefore
      attempted to observe the effects of applying this low-intensity ultrasound to an
      experimental animal model. METHODS: A traumatic brain injury rat model was
      established according to the weight drop method developing the traumatic brain
      edema. The degree of BBBD was measured by the changes in the water content and
      spectrophotometric absorbance of Evans blue dye in the cerebrum after low
      frequency ultrasound. RESULTS: The cerebral water content levels showed that the
      BBBD gradually increased after impact and thereafter decreased after 6 h. After
      low-frequency ultrasound exposure, the values of water content and
      spectrophotometric absorbance of Evans blue dye were the lowest at 0 h, and were
      increased at 2 and 5 h of ultrasonic exposure (after impact). CONCLUSION: We
      suggest that traumatic brain edema in the rat model may be alleviated by low
      frequency ultrasound, and low-frequency ultrasound might be proposed as a novel
      treatment modality for brain edema.

PMID- 23154514
TI  - A novel route to prepare LaNiO3 perovskite-type oxide nanofibers by
      electrospinning for glucose and hydrogen peroxide sensing.
AB  - Perovskite-type oxide LaNiO(3) nanofibers (LNFs) have been successfully
      synthesized by electrospinning and sequential calcinations. The electrospun LNFs
      modified carbon paste electrode was used to construct a nonenzymatic hydrogen
      peroxide (H(2)O(2)) sensor and glucose biosensor for the first time. The LNFs
      composition was verified by X-ray diffraction, and the morphologies were examined
      by scanning electron microscopy and transmission electron microscopy. Cyclic
      voltammetry and amperometry were used to evaluate the catalytic activity of the
      LNFs modified electrode towards H(2)O(2) and glucose. By using LNFs as
      electrocatalysts, the modified electrode showed high electrocatalytic activity
      for the oxidation of H(2)O(2) and glucose. Under the optimized conditions, the
      H(2)O(2) sensor exhibited a low detection limit down to 33.9 nM with a wide
      linear range from 0.05 to 1000 MUM. The nonenzymatic sensor also showed fast
      response, long-term stability as well as a low detection limit for glucose.

PMID- 23154515
TI  - Preparation of graphite-like carbon nitride nanoflake film with strong
      fluorescent and electrochemiluminescent activity.
AB  - The preparation, characterization, fluorescence (FL) and electrochemiluminescence
      (ECL) of graphite-like carbon nitride nanoflake particles (g-C(3)N(4) NFPs) and
      nanoflake films (g-C(3)N(4) NFFs) have been reported. Highly water-dispersible g
      C(3)N(4) NFPs with a height of ~5 to 35 nm and a lateral dimension of ~40 to 220
      nm have been extracted from bulk g-C(3)N(4) materials by chemical oxidation. New,
      stable and defined g-C(3)N(4) NFFs can be easily obtained by drying NFPs on
      certain hydrophilic substrates such as glass or electrode surfaces. Both g
      C(3)N(4) NFPs and g-C(3)N(4) NFFs have good FL activities, i.e. they can give
      strong blue light (435 nm) emission under UV light (365 nm) excitation. The as
      prepared g-C(3)N(4) NFFs on a glassy carbon electrode exhibit strong non-surface
      state ECL activity in the presence of reductive-oxidative coreactants, including
      dissolved oxygen (O(2)), hydrogen peroxide (H(2)O(2)) and peroxydisulfate
      (S(2)O(8)(2-)) and give rise to blue light emission (435 nm), which is the same
      as the wavelength of FL. The non-surface state ECL mechanisms of the g-C(3)N(4)
      NFF-coreactant systems have been studied and discussed in detail.

PMID- 23154517
TI  - Responding to a diagnosis of localized prostate cancer: men's experiences of
      normal distress during the first 3 postdiagnostic months.
AB  - BACKGROUND: Men experience localized prostate cancer (PCa) as aversive and
      distressing. Little research has studied the distress men experience as a normal
      response to PCa, or how they manage this distress during the early stages of the
      illness. OBJECTIVES: The objective of this study was to explore the experience of
      men diagnosed with localized PCa during their first postdiagnostic year. METHODS:
      This constructivist qualitative study interviewed 8 men between the ages of 44
      and 77 years, in their homes, on 2 occasions during the first 3 postdiagnostic
      months. Individual, in-depth semistructured interviews were used to collect the
      data. RESULTS: After an initial feeling of shock, the men in this study worked
      diligently to camouflage their experience of distress through hiding and
      attenuating their feelings and minimizing the severity of PCa. CONCLUSIONS: Men
      silenced distress because they believed it was expected of them. Maintaining
      silence allowed men to protect their strong and stoic self-image. This
      stereotype, of the strong and stoic man, prevented men from expressing their
      feelings of distress and from seeking support from family and friends and health
      professionals. IMPLICATIONS FOR PRACTICE: It is important for nurses to
      acknowledge and recognize the normal distress experienced by men as a result of a
      PCa diagnosis. Hence, nurses must learn to identify the ways in which men avoid
      expressing their distress and develop early supportive relationships that
      encourage them to express and subsequently manage it.

PMID- 23154518
TI  - Simultaneous electroanalytical determination of hydroquinone and catechol in the
      presence of resorcinol at an SiO2/C electrode spin-coated with a thin film of
      Nb2O5.
AB  - This paper describes the development, characterization and application of an
      Nb(2)O(5) film formed on the surface of a carbon ceramic material, SiO(2)/C,
      obtained by a sol-gel method, using the spin-coating technique. The working
      electrode using this material will be designated as SiCNb. Hydroquinone and
      catechol can be oxidized at this electrode in the presence of resorcinol,
      allowing their simultaneous detection. The electrochemical properties of the
      resulting electrode were investigated using cyclic and differential pulse
      voltammetry techniques. Well-defined and separated oxidation peaks were observed
      by differential pulse voltammetry in Tris-HCl buffer solution at pH 7 containing
      1 mol L(-1) KCl in the supporting electrolyte solution. The SiCNb electrode
      exhibited high sensitivity in the simultaneous determination of hydroquinone and
      catechol in the presence of resorcinol, with the limits of detection for
      hydroquinone and catechol being 1.6 MUmol L(-1) and 0.8 MUmol L(-1),
      respectively. Theoretical calculations were performed to determine the ionization
      energies of hydroquinone, catechol and resorcinol; the results were used to
      explain the simultaneous determination of species by differential pulse
      voltammetry. The presence of resorcinol did not produce any interference in the
      simultaneous detection of hydroquinone and catechol on the surface of the
      modified electrode.

PMID- 23154516
TI  - The PRO-SELF pain control program improves family caregivers' knowledge of cancer
      pain management.
AB  - BACKGROUND: The majority of cancer treatment is provided in outpatient settings.
      Family caregivers' (FCs') knowledge and beliefs about pain and its management are
      critical components of effective care. OBJECTIVE: This study's aim was to
      evaluate the efficacy of a psychoeducational intervention, compared with control,
      to increase FCs' knowledge of cancer pain management. INTERVENTION/METHODS:
      Family caregivers of oncology outpatients were randomized together with the
      patients into the PRO-SELF Pain Control Program (n = 58) or a control group (n =
      54). Family caregivers completed a demographic questionnaire and the Family Pain
      Questionnaire (FPQ) at the beginning and end of the study to assess their
      knowledge about pain and its management. The intervention consisted of nurse
      coaching, home visits, and phone calls that occurred over 6 weeks. RESULTS: One
      hundred twelve FCs (60% female) with a mean age of 63 (SD, 10.7) years
      participated. Compared with FCs in the control group, FCs in the PRO-SELF group
      had significantly higher knowledge scores on all of the single items on the FPQ,
      except for the item "cancer pain can be relieved," as well as for the total FPQ
      score. CONCLUSION: The use of a knowledge and attitude survey like the FPQ, as
      part of a psychoeducational intervention provides an effective foundation for FC
      education about cancer pain management. IMPLICATIONS FOR PRACTICE: Oncology
      nurses can use FCs' responses to the FPQ to individualize teaching and spend more
      time on identified knowledge deficits. This individualized approach to FC
      education may save staff time and improve patient outcomes.

PMID- 23154519
TI  - Percutaneous cytologic diagnosis of solid pseudopapillary tumors of pancreas in
      children.
AB  - Solid pseudopapillary tumors of the pancreas, formerly known as Frantz tumors,
      are rare exocrine tumors that electively affect young women in their second and
      third decades of life, and are rarely observed in children. Histologic
      confirmation is nevertheless desirable before proceeding with treatment of
      pancreatic lesions, as appropriate treatment can range from conservative to
      ablative surgery. Here, we report 3 cases of solid pseudopapillary tumors of the
      pancreas and we postulate that percutaneous cytologic sample analysis (instead of
      biopsy) may be sufficient to reach an accurate diagnosis and eliminate
      differential diagnosis.

PMID- 23154520
TI  - Paraganglioma presenting with marked proteinuria: a case report.
AB  - Paragangliomas are rare neuroendocrine tumors that arise from sympathetic and
      parasympathetic paraganglia. In children, most of them are functional tumors.
      Presenting symptoms such as sustained or paroxysmal elevations in blood pressure,
      headache, sweating, and palpitations are related to catecholamine hypersecretion.
      A previously healthy 8-year-old boy presented with marked proteinuria,
      hypertension, and heart murmur. Imaging revealed an 81*43*45 mm sized solid mass
      extending from right retroaortic area to left suprarenal region. Measurements of
      catecholamines suggested the diagnosis of paraganglioma. Pathologic examination
      confirmed the diagnosis. Complete tumor resection was performed. Proteinuria,
      hypertension, and cardiac signs resolved after surgery. Proteinuria has been
      described as a rare manifestation of paragangliomas in adult patients. This is
      the first case of a paraganglioma presenting with massive proteinuria in a child.

PMID- 23154522
TI  - Combining transition metal catalysis and organocatalysis--an update.
AB  - The combination of transition metal catalysis and organocatalysis as a new and
      exciting research area has attracted increasing attention as it can enable the
      development of unprecedented transformations that is not possible by use of
      either of the catalytic systems alone, and can improve the reactivity, efficiency
      and stereocontrol of existing chemical transformations. In this review, we
      summarize recent remarkable progress in the field of combined transition metal
      catalysis and organocatalysis, further highlighting the potential of this new and
      exciting research area and the many challenges that still remain for the future.

PMID- 23154521
TI  - Structural and electrical characterization of ultra-thin SrTiO3 tunnel barriers
      grown over YBa2Cu3O7 electrodes for the development of high Tc Josephson
      junctions.
AB  - The transport properties of ultra-thin SrTiO(3) (STO) layers grown over
      YBa(2)Cu(3)O(7) electrodes were studied by conductive atomic force microscopy at
      the nano-scale. A very good control of the barrier thickness was achieved during
      the deposition process. A phenomenological approach was used to obtain critical
      parameters regarding the structural and electrical properties of the system. The
      STO layers present an energy barrier of 0.9 eV and an attenuation length of 0.23
      nm, indicating very good insulating properties for the development of high
      quality Josephson junctions.

PMID- 23154524
TI  - Ethical dilemmas associated with genetic testing: which are most commonly seen
      and how are they managed?
AB  - PURPOSE: The aim of this study was to document the range and frequency of ethical
      dilemmas associated with genetic testing encountered by genetic health
      professionals and to determine the strategies used to manage them. METHODS: An
      online survey was used to document how often the 11 key ethical dilemmas have
      been encountered; whether any additional dilemmas have been encountered; and how
      these dilemmas have been managed. Members of the Australasian Association of
      Clinical Geneticists, Australasian Society of Genetic Counsellors, and genetic
      social workers practicing in Australia and New Zealand were invited to
      participate. RESULTS: A total of 102 responses were received (31% response rate).
      Respondents had encountered all of the 11 ethical dilemmas included in the
      survey, and 18 respondents had encountered 14 additional dilemmas. Respondents
      encountered an average of 2.2 dilemmas per year of practice. Peer and clinical
      supervision were the most common strategies used to manage dilemmas, and seeking
      advice from clinical ethics committees was rare. Occasionally, respondents
      facilitated practices they deemed unethical as a consequence of client deception.
      CONCLUSION: Ethical dilemmas of genetic testing are encountered regularly in
      clinical genetics practice. Evidence provided by our study can assist in
      targeting training, support, and guidance to help genetic health professionals
      navigate such dilemmas in the future.

PMID- 23154523
TI  - Comparative analysis of IRF6 variants in families with Van der Woude syndrome and
      popliteal pterygium syndrome using public whole-exome databases.
AB  - PURPOSE: Mutations in the transcription factor IRF6 cause allelic autosomal
      dominant clefting syndromes, Van der Woude syndrome, and popliteal pterygium
      syndrome. We compared the distribution of IRF6 coding and splice-site mutations
      from 549 families with Van der Woude syndrome or popliteal pterygium syndrome
      with that of variants from the 1000 Genomes and National Heart, Lung, and Blood
      Institute Exome Sequencing Projects. METHODS: We compiled all published
      pathogenic IRF6 mutations and performed direct sequencing of IRF6 in families
      with Van der Woude syndrome or popliteal pterygium syndrome. RESULTS: Although
      mutations causing Van der Woude syndrome or popliteal pterygium syndrome were
      nonrandomly distributed with significantly increased frequencies in the DNA
      binding domain (P = 0.0001), variants found in controls were rare and evenly
      distributed in IRF6. Of 194 different missense or nonsense variants described as
      potentially pathogenic, we identified only two in more than 6,000 controls.
      PolyPhen and SIFT (sorting intolerant from tolerant) reported 5.9% of missense
      mutations in patients as benign, suggesting that use of current in silico
      prediction models to determine function can have significant false negatives.
      CONCLUSION: Mutation of IRF6 occurs infrequently in controls, suggesting that for
      IRF6 there is a high probability that disruption of the coding sequence,
      particularly the DNA-binding domain, will result in syndromic features. Prior
      associations of coding sequence variants in IRF6 with clefting syndromes have had
      few false positives.

PMID- 23154525
TI  - Perspectives of surrogate decision makers for critically ill patients regarding
      gene variation research.
AB  - PURPOSE: We undertook this investigation to explore the manner in which surrogate
      decision makers for critically ill patients perceived genetic data collected in
      the context of clinical investigation. METHODS: Surrogate decision makers for
      critically ill patients cared for in intensive care units of two urban hospitals
      participated in focus groups designed to explore perceptions regarding gene
      variation research. RESULTS: Surrogate decision makers were generally familiar
      with genetic concepts and reported that they could provide an informed opinion
      regarding permitting (or declining) the participation of their loved ones in gene
      variation research. Respondents perceived the risk associated with this type of
      research largely as the risk associated with acquiring the sample (i.e., whether
      it involved an invasive procedure or not) but appreciated that genetic samples
      could provide information not readily obtained from nongenetic sources. Concerns
      about potential misuse of genetic data largely centered on misconduct, paternity,
      forensic applications, and insurance and employment discrimination. Although
      surrogate decision makers expressed that their loved ones would have interest in
      return of results and being recontacted for future use, these interests were
      secondary to confidentiality concerns. CONCLUSION: Respondents perceived genetic
      and nongenetic data as comparable. Informed consent processes that provide clear
      information regarding confidentiality protections, specimen handling, and
      parameters for future use may enhance enrollment.Genet Med 2013:15(5):368-373.

PMID- 23154526
TI  - Different cilia response to adenosine triphosphate or benzalkonium chloride
      treatment in mouse nasal and tracheal culture.
AB  - OBJECTIVES: Our purpose was to compare the ciliary function between the upper and
      lower airway. METHODS: Basal ciliary beat frequency (CBF) and changes in CBF in
      response to exogenous stimuli [adenosine triphosphate (ATP) or benzalkonium
      chloride (BAC)] of primary cultured mouse nasal and tracheal epithelial cells
      were quantified using digital microscopy combined with a beat-by-beat CBF
      analysis. RESULTS: The basal CBF of the mouse tracheal culture was statistically
      higher than the nasal culture. Adding 10 or 100 uM ATP caused an increase of CBF
      in both mouse nasal and tracheal cultures; however, nasal culture induced a more
      robust increase of CBF than tracheal culture. Treatment with 0.001% BAC increased
      CBF within 2 min after treatment and then CBF gradually decreased; nasal and
      tracheal culture manifested a similar change in CBF. With a concentration of
      0.01%, BAC induced a rapid and time-dependent decrease of CBF in both mouse nasal
      and tracheal cultures; however, tracheal culture showed a blunter response to
      this ciliotoxic agent, with the ciliary beating duration time distinguishably
      longer than in the nasal culture. CONCLUSION: The inherent ciliary and
      physiological function is different in the upper and lower airway in mice.

PMID- 23154527
TI  - Refining the diagnosis and prognostic categorization of acute myeloid leukemia
      patients with an integrated use of cytogenetic and molecular studies.
AB  - Significant progress in the understanding of the genetic basis of acute myeloid
      leukemia (AML) has been made during the last 30 years. The aim of the present
      study was to assess whether the detection of recurrent gene rearrangements by
      fluorescent in situ hybridization (FISH) studies and NPM1 and FLT3 gene mutations
      by molecular studies added clinically relevant information to the karyotype in
      113 AML patients. Thus, FISH and molecular studies were found to add new
      information in 22 and 55% of the patients, respectively, particularly in cases
      with normal karyotype (NK) or when a cytogenetic analysis failed. Patients with
      NK changed their genetic risk group to favorable in 27 and 29% of cases using
      FISH and molecular biology studies, respectively. Our results demonstrate that
      molecular biology and FISH studies provide relevant information in AML and should
      be routinely performed.

PMID- 23154528
TI  - Challenging false discovery rate: a partition test based on p values in human
      case-control association studies.
AB  - BACKGROUND/AIMS: We consider the situation that multiple genetic variants are
      underlying a heritable trait and assume that each contributes to the trait only
      to a small degree. The aim is to develop a statistical test for disease
      association of these multiple variants. METHODS: We expect that p values
      resulting from a genome-wide case-control association analysis will fall into two
      classes: those reflecting true association and those occurring randomly in the
      interval from 0 to 1. We develop a partition test to find the set of smallest p
      values deviating most from the number of p values expected under randomness.
      RESULTS: Power calculations demonstrate the superiority of our partition test
      over conventional SNP-by-SNP analyses. Applications of the partition test to six
      published datasets show that our test is particularly suitable when multiple SNPs
      appear to contribute to a trait, and furnished more significant results than a
      well-known procedure to estimate the false discovery rate. CONCLUSIONS: Our
      partition test also furnishes an estimate of the number of functional SNPs
      underlying disease and can be highly significant, while single-locus tests may be
      far from significant.

PMID- 23154529
TI  - 1,5-(H, RO, RS) shift/6pi-electrocyclic ring closure tandem processes on N
      [(alpha-heterosubstituted)-2-tolyl]ketenimines: a case study of relative
      migratory aptitudes and activating effects.
AB  - A number of N-aryl ketenimines, substituted at the ortho position either with
      different non-cyclic acetalic functions (acetals, monothioacetals, dithioacetals)
      or with only one alkoxymethyl or (alkylthio)methyl group, have been prepared and
      submitted to thermal treatment in toluene solution. Under smooth heating the
      ketenimines bearing non-cyclic acetals converted into 3,4-dihydroquinolines
      following two competitive tandem sequences that involve the alternative 1,5
      migration of a hydride or alkoxy group as the first mechanistic step, followed by
      subsequent 6pi electrocyclic ring closure. The heterocumulenes bearing acyclic
      monothioacetal and dithioacetal functions converted via a unique consecutive
      process involving the selective migration of the alkanethiolate group.
      Ketenimines bearing only one ether or thioether group transformed exclusively by
      the tandem sequence initiated by a 1,5 hydride shift. All these transformations
      provided as final reaction products a variety of quinoline derivatives with a
      range of substitution patterns. From these experiments the following order of
      propensity to migration can be extracted: RS > RO > H. It was also possible to
      estimate the following order of relative activating activities: RO > RS > H.

PMID- 23154530
TI  - Central obesity and smoking are key modifiable risk factors for elevated C
      reactive protein in Asian individuals who are not eligible for statin therapy.
AB  - OBJECTIVE: Statin therapy reduces coronary heart disease (CHD) and mortality in
      individuals with elevated C-reactive protein (CRP) but low-density lipoprotein
      cholesterol below the threshold at which statin therapy is recommended. We
      determined the proportion of individuals with elevated CRP in whom statin therapy
      was not indicated, and examined predictors for elevated CRP in a multi-ethnic
      Asian population. DESIGN: We studied 3404 participants (Chinese, Malays and Asian
      Indians) without a history of hypercholesterolemia living in Singapore (mean
      age+/-s.d.: 48.9+/-11.2 years). Eligibility for statin therapy was determined
      based on the National Cholesterol Education Program (NCEP) Expert Panel on
      Detection, Evaluation and Treatment of High Blood Cholesterol in Adults (Adult
      Treatment Panel III (ATPIII)) guideline. CRP was measured by high-sensitivity
      enzyme-linked immunosorbent assay method. CRP level greater than 2 mg l(-1) was
      considered as elevated. RESULTS: Elevated CRP was found in 29.3% participants who
      were not eligible for statin therapy (n=2974). Elevated CRP was more common in
      females and amongst those of Malay or Asian-Indian ethnicity. Compared with
      participants with low CRP, those with elevated CRP were shown to have higher
      levels of obesity, blood pressure, triglyceride and insulin resistance (IR), but
      lower high-density lipoprotein cholesterol levels (all Ps<0.001). After
      multivariate analysis, gender (odds ratio (OR) 3.34 for females), ethnicity
      (Malay OR 1.57, 95% confidence interval (CI) 1.25-1.96; Asian-Indian OR 1.97, 95%
      CI 1.55-2.50), waist circumference (OR 1.06, 95% CI 1.05-1.07), smoking (OR 1.49,
      95% CI 1.08-2.05) and IR (OR 1.14, 95% CI 1.07-1.22) were significant predictors
      of CRP (all Ps--values<0.05). CONCLUSION: Routine measurement of CRP identifies a
      substantial number of Asian individuals at risk of CHD in whom statin therapy is
      not currently indicated, particularly in women and certain ethnic groups (Malays
      and Asian Indians). Weight loss and smoking cessation are important measures to
      reduce the proportion of individuals with elevated CRP.

PMID- 23154531
TI  - Sensing applications of synthetic transport systems.
AB  - This feature article offers a comprehensive account of a decade of research
      devoted to the combination of the grand sensing principles with synthetic
      transport systems that act in lipid bilayers. Differential sensing, that is
      pattern generation and pattern recognition, is exemplified with an artificial
      nose. The aptamer version of immunosensing is realized with sticky-end polymers
      of DNA double helices for both signal generation and signal transduction.
      Biosensing, that is the use of enzymes for signal generation, is exemplified
      first with an artificial tongue and then expanded to analytes such as
      cholesterol, phytate or polyphenols. Enjoyable also for the general reader, we
      hope that this account will inspire supramolecular organic as well as analytical,
      physical and biological chemists.

PMID- 23154532
TI  - Long term effects of the implantation of Wharton's jelly-derived mesenchymal stem
      cells from the umbilical cord for newly-onset type 1 diabetes mellitus.
AB  - Type 1 diabetes mellitus (T1DM) is an autoimmune disorder resulted from T cell
      mediated destruction of pancreatic beta-cells, how to regenerate beta-cells and
      prevent the autoimmune destruction of remnant and neogenetic beta-cells is a
      tough problem. Immunomodulatory propertity of mesenchymal stem cell make it
      illuminated to overcome it. We assessed the long-term effects of the implantation
      of Wharton's jelly-derived mesenchymal stem cells (WJ-MSCs) from the umbilical
      cord for Newly-onset T1DM. Twenty-nine patients with newly onset T1DM were
      randomly divided into two groups, patients in group I were treated with WJ-MSCs
      and patients in group II were treated with normal saline based on insulin
      intensive therapy. Patients were followed-up after the operation at monthly
      intervals for the first 3 months and thereafter every 3 months for the next 21
      months, the occurrence of any side effects and results of laboratory examinations
      were evaluated. There were no reported acute or chronic side effects in group I
      compared with group II, both the HbA1c and C peptide in group I patients were
      significantly better than either pretherapy values or group II patients during
      the follow-up period. These data suggested that the implantation of WJ-MSCs for
      the treatment of newly-onset T1DM is safe and effective. This therapy can restore
      the function of islet beta cells in a longer time, although precise mechanisms
      are unknown, the implantation of WJ-MSCs is expected to be an effective strategy
      for treatment of type1 diabetes.

PMID- 23154533
TI  - The onset of antineutrophil cytoplasmic antibody-associated vasculitis
      immediately after methimazole was switched to propylthiouracil in a woman with
      Graves' disease who wished to become pregnant.
AB  - Propylthiouracil (PTU) is recommended as a first-line antithyroid drug (ATD)
      during first trimester organogenesis in pregnancy because recent evidence
      suggests that methimazole (MMI) may be associated with congenital anomalies.
      However, PTU more commonly causes myeloperoxidase (MPO)-antineutrophil
      cytoplasmic antibody (ANCA)-associated vasculitis, which usually occurs during
      prolonged treatment, compared with MMI. We report a case of MPO-ANCA-associated
      vasculitis in a 35-year-old woman with Graves'disease. Although her thyroid
      function could be maintained euthyroid by MMI, her ATD was switched to PTU
      because she wished to become pregnant. The patient presented with flu-like
      symptoms 8 days after starting PTU and developed hemoptysis and dyspnea at 22
      days. Her MPO-ANCA titer was 21 ELISA units (EUs) before PTU treatment but
      increased to 259 EUs at 22 days after PTU treatment. Her clinical condition
      improved with the discontinuation of PTU and with immunosuppressive therapy. This
      case indicated that MPO-ANCA vasculitis occurred within several weeks after the
      initiation of PTU and that this side effect could be caused by the change from
      MMI to PTU. Thus, our clinical observation suggests that patients treated with
      PTU should be carefully monitored for MPO-ANCA titers and variable manifestations
      of MPO-ANCA-associated vasculitis regardless of the period of administration.

PMID- 23154534
TI  - One divinyl reductase reduces the 8-vinyl groups in various intermediates of
      chlorophyll biosynthesis in a given higher plant species, but the isozyme differs
      between species.
AB  - Divinyl reductase (DVR) converts 8-vinyl groups on various chlorophyll
      intermediates to ethyl groups, which is indispensable for chlorophyll
      biosynthesis. To date, five DVR activities have been detected, but adequate
      evidence of enzymatic assays using purified or recombinant DVR proteins has not
      been demonstrated, and it is unclear whether one or multiple enzymes catalyze
      these activities. In this study, we systematically carried out enzymatic assays
      using four recombinant DVR proteins and five divinyl substrates and then
      investigated the in vivo accumulation of various chlorophyll intermediates in
      rice (Oryza sativa), maize (Zea mays), and cucumber (Cucumis sativus). The
      results demonstrated that both rice and maize DVR proteins can convert all of the
      five divinyl substrates to corresponding monovinyl compounds, while both cucumber
      and Arabidopsis (Arabidopsis thaliana) DVR proteins can convert three of them.
      Meanwhile, the OsDVR (Os03g22780)-inactivated 824ys mutant of rice exclusively
      accumulated divinyl chlorophylls in its various organs during different
      developmental stages. Collectively, we conclude that a single DVR with broad
      substrate specificity is responsible for reducing the 8-vinyl groups of various
      chlorophyll intermediates in higher plants, but DVR proteins from different
      species have diverse and differing substrate preferences, although they are
      homologous.

PMID- 23154535
TI  - Regulation of miR399f transcription by AtMYB2 affects phosphate starvation
      responses in Arabidopsis.
AB  - Although a role for microRNA399 (miR399) in plant responses to phosphate (Pi)
      starvation has been indicated, the regulatory mechanism underlying miR399 gene
      expression is not clear. Here, we report that AtMYB2 functions as a direct
      transcriptional activator for miR399 in Arabidopsis (Arabidopsis thaliana) Pi
      starvation signaling. Compared with untransformed control plants, transgenic
      plants constitutively overexpressing AtMYB2 showed increased miR399f expression
      and tissue Pi contents under high Pi growth and exhibited elevated expression of
      a subset of Pi starvation-induced genes. Pi starvation-induced root architectural
      changes were more exaggerated in AtMYB2-overexpressing transgenic plants compared
      with the wild type. AtMYB2 directly binds to a MYB-binding site in the miR399f
      promoter in vitro, as well as in vivo, and stimulates miR399f promoter activity
      in Arabidopsis protoplasts. Transcription of AtMYB2 itself is induced in response
      to Pi deficiency, and the tissue expression patterns of miR399f and AtMYB2 are
      similar. Both genes are expressed mainly in vascular tissues of cotyledons and in
      roots. Our results suggest that AtMYB2 regulates plant responses to Pi starvation
      by regulating the expression of the miR399 gene.

PMID- 23154537
TI  - Cubic regression-based degree of correction predicts the performance of whole
      bisulfitome amplified DNA methylation analysis.
AB  - Epigenetic mechanisms, including DNA methylation, are important determinants in
      development and disease. There is a need for technologies capable of detecting
      small variations in methylation levels in an accurate and reproducible manner,
      even if only limited amounts of DNA are available (which is the case in many
      studies in humans). Quantitative methylation analysis of minute DNA amounts after
      whole bisulfitome amplification (qMAMBA) has been proposed as an alternative, but
      this technique has not been adequately standardized and no comparative study
      against conventional methods has been performed, that includes a wide range of
      methylation percentages and different target assays. We designed an experiment to
      compare the performance of qMAMBA and bisulfite-treated genomic (non-amplified)
      DNA pyrosequencing. Reactions were performed in duplicate for each technique in
      eight different target genes, using nine artificially constructed DNA samples
      with methylation levels ranging between 0% and 100% with intervals of 12.5%.
      Cubic polynomial curves were plotted from the experimental results and the real
      methylation values and the resulting equation was used to estimate new corrected
      data points. The use of the cubic regression-based correction benefits the
      accuracy and the power of discrimination in methylation studies. Additionally,
      dispersion of the new estimated data around a y = x line (R ( 2) ) served to fix
      a cutoff that can discriminate, with a single 9-point curve experiment, whether
      whole bisulfitome amplification and subsequent qMAMBA can produce accurate
      methylation results. Finally, even with an optimized reagent kit, DNA samples
      subjected to whole bisulfitome amplification enhance the preferential
      amplification of unmethylated alleles, and subtle changes in methylation levels
      cannot be detected confidently.

PMID- 23154536
TI  - Chlamydomonas reinhardtii chloroplasts contain a homodimeric pyruvate:ferredoxin
      oxidoreductase that functions with FDX1.
AB  - Eukaryotic algae have long been known to live in anoxic environments, but
      interest in their anaerobic energy metabolism has only recently gained momentum,
      largely due to their utility in biofuel production. Chlamydomonas reinhardtii
      figures remarkably in this respect, because it efficiently produces hydrogen and
      its genome harbors many genes for anaerobic metabolic routes. Central to
      anaerobic energy metabolism in many unicellular eukaryotes (protists) is
      pyruvate:ferredoxin oxidoreductase (PFO), which decarboxylates pyruvate and forms
      acetyl-coenzyme A with concomitant reduction of low-potential ferredoxins or
      flavodoxins. Here, we report the biochemical properties of the homodimeric PFO of
      C. reinhardtii expressed in Escherichia coli. Electron paramagnetic resonance
      spectroscopy of the recombinant enzyme (Cr-rPFO) showed three distinct [4Fe-4S]
      iron-sulfur clusters and a thiamine pyrophosphate radical upon reduction by
      pyruvate. Purified Cr-rPFO exhibits a specific decarboxylase activity of 12 umol
      pyruvate min-1 mg-1 protein using benzyl viologen as electron acceptor. Despite
      the fact that the enzyme is very oxygen sensitive, it localizes to the
      chloroplast. Among the six known chloroplast ferredoxins (FDX1-FDX6) in C.
      reinhardtii, FDX1 and FDX2 were the most efficient electron acceptors from Cr
      rPFO, with comparable apparent K(m) values of approximately 4 um. As revealed by
      immunoblotting, anaerobic conditions that lead to the induction of CrPFO did not
      increase levels of either FDX1 or FDX2. FDX1, being by far the most abundant
      ferredoxin, is thus likely the partner of PFO in C. reinhardtii. This finding
      postulates a direct link between CrPFO and hydrogenase and provides new
      opportunities to better study and engineer hydrogen production in this protist.

PMID- 23154538
TI  - Pyruvate kinase is a dosage-dependent regulator of cellular amino acid
      homeostasis.
AB  - The glycolytic enzyme pyruvate kinase (PK) is required for cancer development,
      and has been implicated in the metabolic transition from oxidative to
      fermentative metabolism, the Warburg effect. However, the global metabolic
      response that follows changes in PK activity is not yet fully understood. Using
      shotgun proteomics, we identified 31 yeast proteins that were regulated in a PK
      dependent manner. Selective reaction monitoring confirmed that their expression
      was dependent on PK isoform, level and activity. Most of the PK targets were
      amino acid metabolizing enzymes or factors of protein translation, indicating
      that PK plays a global regulatory role in biosynthethic amino acid metabolism.
      Indeed, we found strongly altered amino acid profiles when PK levels were
      changed. Low PK levels increased the cellular glutamine and glutamate
      concentrations, but decreased the levels of seven amino acids including serine
      and histidine. To test for evolutionary conservation of this PK function, we
      quantified orthologues of the identified PK targets in thyroid follicular
      adenoma, a tumor characterized by high PK levels and low respiratory activity.
      Aminopeptidase AAP-1 and serine hydroxymethyltransferase SHMT1 both showed PKM2-
      concentration dependence, and were upregulated in the tumor. Thus, PK expression
      levels and activity were important for maintaining cellular amino acid
      homeostasis. Mediating between energy production, ROS clearance and amino acid
      biosynthesis, PK thus plays a central regulatory role in the metabolism of
      proliferating cells.

PMID- 23154540
TI  - Comparison of NT-proBNP levels in hemodialysis versus peritoneal dialysis
      patients.
AB  - BACKGROUND: Plasma N-terminal fragment of pro brain natriuretic peptide (NT
      proBNP) concentration is elevated in cardiovascular diseases such as congestive
      heart failure, where increased levels of NT-proBNP indicate cardiac dysfunction,
      hypervolemia, and higher risk of hospitalization and death. These associations
      apply also to patients with severe impairment of kidney function. Little is known
      about diferences in plasma level of NT-proBNP in patients receiving hemodialysis
      (HD) versus those receiving continuous ambulatory peritoneal dialysis (CAPD).
      AIM: To evaluate differences in plasma NT-proBNP concentration between HD and
      CAPD patients. METHODS: Plasma NT-proBNP concentration was prospectively measured
      in consecutive patients receiving either HD or CAPD at our hospital center. All
      other standard clinical parameters were recorded. The correlation between plasma
      NT-proBNP concentration and the type of dialysis was then examined. RESULTS: We
      studied 99 consecutive patients on HD (age 62 +/- 15 years, 66% male) and 18
      consecutive patients on CAPD (age 56 +/- 18 years, 67% male). Both groups had
      similar baseline characteristics including duration of dialysis, left ventricular
      function and mass, and cardiothoracic ratio. Significantly more patients on HD
      had abnormal NT-proBNP levels compared to patients on CAPD (97% vs 44%;
      P<0.0001), and this difference remained highly significant when using various NT
      proBNP cut off values. A subgroup analysis revealed that the lower NT-proBNP
      levels of CAPD patients are most pronounced in patients with preserved left
      ventricular ejection function. As expected, NT-proBNP levels correlated
      negatively with left ventricular function and positively with cardiothoracic
      ratio, and this applied to both HD and CAPD groups. CONCLUSION: The lower
      concentration of NT-proBNP in patients on CAPD compared to those on HD suggests
      that CAPD produces lesser hemodynamic stress, especially in patients with
      preserved left ventricular systolic function. Even though increased NT-proBNP
      levels have been shown to predict increased morbidity and mortality, further
      studies are necessary to assess the long term benefit of CAPD compared to HD.

PMID- 23154539
TI  - Small regulatory RNAs controlled by genomic imprinting and their contribution to
      human disease.
AB  - More than a hundred protein-coding genes are controlled by genomic imprinting in
      humans. These atypical genes are organized in chromosomal domains, each of which
      is controlled by a differentially methylated "imprinting control region" (ICR).
      How ICRs mediate the parental allele-specific expression of close-by genes is now
      becoming understood. At several imprinted domains, this epigenetic mechanism
      involves the action of long non-coding RNAs. It is less well appreciated that
      imprinted gene domains also transcribe hundreds of microRNA and small nucleolar
      RNA genes and that these represent the densest clusters of small RNA genes in
      mammalian genomes. The evolutionary reasons for this remarkable enrichment of
      small regulatory RNAs at imprinted domains remain unclear. However, recent
      studies show that imprinted small RNAs modulate specific functions in development
      and metabolism and also are frequently perturbed in cancer. Here, we review our
      current understanding of imprinted small RNAs in the human genome and discuss how
      perturbation of their expression contributes to disease.

PMID- 23154541
TI  - Endovascular brain intervention and mapping in a dog experimental model using
      magnetically-guided micro-catheter technology.
AB  - AIM: Despite the substantial progress that has been achieved in interventional
      cardiology and cardiac electrophysiology, endovascular intervention for the
      diagnosis and treatment of central nervous system (CNS) disorders such as stroke,
      epilepsy and CNS malignancy is still limited, particularly due to highly tortuous
      nature of the cerebral arterial and venous system. Existing interventional
      devices and techniques enable only limited and complicated access especially into
      intra-cerebral vessels. The aim of this study was to develop a micro-catheter
      magnetically-guided technology specifically designed for endovascular
      intervention and mapping in deep CNS vascular structures. METHODS: Mapping of
      electrical brain activity was performed via the venous system on an animal dog
      model with the support of the NIOBE II system. RESULTS: A novel micro-catheter
      specially designed for endovascular interventions in the CNS, with the support of
      the NIOBE II technology, was able to reach safely deep intra-cerebral venous
      structures and map the electrical activity there. Such structures are not
      currently accessible using standard catheters. CONCLUSION: This is the first
      study demonstrating successful use of a new micro-catheter in combination with
      NIOBE II technology for endovascular intervention in the brain.

PMID- 23154542
TI  - EGFR gene mutations: is it prognostic or predictive in surgically resected lung
      cancer?

PMID- 23154543
TI  - The achilles' heel of lung cancer resection in the United States.

PMID- 23154544
TI  - Interpretation of PET scans: do not take SUVs at face value.

PMID- 23154545
TI  - G-protein coupled receptor family C, group 5, member A (GPRC5A) expression is
      decreased in the adjacent field and normal bronchial epithelia of patients with
      chronic obstructive pulmonary disease and non-small-cell lung cancer.
AB  - INTRODUCTION: Understanding oncogenes and tumor suppressor genes expression
      patterns is essential for characterizing lung cancer pathogenesis. We have
      previously demonstrated that mGprc5a/hGPRC5A is a lung-specific tumor suppressor
      evidenced by inflammation-mediated tumorigenesis in Gprc5a-knockout mice. The
      implication of GPRC5A in human lung cancer pathogenesis, including that
      associated with inflammatory chronic obstructive pulmonary disease (COPD), a risk
      factor for the malignancy, remains elusive. METHODS: We sought to examine GPRC5A
      immunohistochemical expression in histologically normal bronchial epithelia (NBE)
      from lung disease-free never- and ever-smokers (n = 13 and n = 18, respectively),
      from COPD patients with (n = 26) and without cancer (n = 24) and in non-small
      cell lung cancers (NSCLCs) (n = 474). Quantitative assessment of GPRC5A
      transcript expression in airways (n = 6), adjacent NBEs (n = 29) and
      corresponding tumors (n = 6) from 6 NSCLC patients was also performed. RESULTS:
      GPRC5A immunohistochemical expression was significantly lower in tumors compared
      to uninvolved NBE (p < 0.0001) and was positively associated with adenocarcinoma
      histology (p < 0.001). GPRC5A airway expression was highest in lung disease-free
      NBE, decreased and intermediate in NBE of cancer-free COPD patients (p = 0.004)
      and further attenuated and lowest in epithelia of COPD patients with
      adenocarcinoma and SCC (p < 0.0001). Furthermore, GPRC5A mRNA was significantly
      decreased in NSCLCs and corre sponding NBE compared to uninvolved normal lung (p
      = 0.03). CONCLUSIONS: Our findings highlight decreased GPRC5A expression in the
      field cancerization of NSCLC, including that associated with lung inflammation.
      Assessment of the use of GPRC5A expression as a risk factor for NSCLC development
      in COPD patients is warranted.

PMID- 23154546
TI  - A pilot characterization of human lung NSCLC by protein pathway activation
      mapping.
AB  - BACKGROUND: An understanding of the activated protein signaling architecture in
      non-small-cell lung cancer (NSCLC) is of critical importance to the development
      of new therapeutic approaches and identification of predictive and prognostic
      biomarkers for patient stratification. METHODS: We used reverse-phase protein
      microarrays to map the activated protein signaling networks of 47 NSCLC tumors,
      28 of which were node negative, which were subjected to tumor cellular enrichment
      using laser capture microdissection. The phosphorylation/cleavage levels of 111
      key signaling proteins and total levels of 17 proteins were measured for
      broadscale signaling analysis. RESULTS: Pathway activation mapping of NSCLC
      revealed distinct subgroups composed of epidermal growth factor receptor (ERBB1),
      v-erb-b2 erythroblastic leukemia viral oncogene homolog 2 (ERBB2), v-erb-b2
      erythroblastic leukemia viral oncogene homolog 3 (ERBB3), v-erb-a erythroblastic
      leukemia viral oncogene homolog 4 (ERBB4), v-akt murine thymoma viral oncogene
      homolog 1- mammalian target of rapamycin (AKT-mTOR), protein kinase, AMP
      activated, alpha 2 catalytic subunit (AMPK), and autophagy-related signaling,
      along with transforming growth factor-beta-signaling protein 1 (SMAD), insulin
      line growth factor receptor (IGFR), rearranged during transfection proto-oncogene
      (RET), and activated CDC42-associated kinase (ACK) activation. Investigation of
      epidermal growth factor receptor (EGFR)-driven signaling identified a unique
      cohort of tumors with low EGFR protein expression yet high relative levels of
      phosphorylated EGFR and high EGFR total protein with low relative levels of
      phosphorylation. Last, mapping analysis of patients with NSCLC with N0 disease
      revealed a pilot pathway activation signature composed of linked epidermal growth
      factor receptor family (HER)-AMPK-AKT-mTOR signaling network along with focal
      adhesion kinase- LIM domain kinase-1 (FAK-LIMK) and janus kinase (JAK)-signal
      transducers and activators of transcription (STAT) pathways that correlated with
      short-term survival and aggressive disease. CONCLUSIONS: Functional protein
      pathway activation mapping of NSCLC reveals distinct activation subgroups that
      are underpinned by important therapeutic targets and that patients with early
      stage node negative disease and poor prognosis may be identified by activation of
      defined, biochemically linked protein signaling events. Such findings, if
      confirmed in larger study sets, could help select and stratify patients for
      personalized targeted therapies.

PMID- 23154547
TI  - The introduction of systematic genomic testing for patients with non-small-cell
      lung cancer.
AB  - BACKGROUND: Genomic testing to identify driver mutations that enable targeted
      therapy is emerging for patients with non-small-cell lung cancer (NSCLC). We
      report the implementation of systematic prospective genotyping for somatic
      alterations in BRAF, PIK3CA, HER2, and ALK, in addition to EGFR and KRAS, in
      NSCLC patients at the Dana-Farber Cancer Institute. METHODS: Patients with NSCLC
      were prospectively referred by their providers for clinical genotyping. Formalin
      fixed, paraffin embedded tumor samples were analyzed by Sanger sequencing for
      mutations in selected exons of EGFR, KRAS, BRAF, PIK3CA, and HER2. ALK
      rearrangements were detected by fluorescence in situ hybridization or
      immunohistochemistry. RESULTS: Between July 1, 2009 and August 1, 2010, 427
      specimens from 419 patients were referred for genomic characterization; 344 (81%)
      specimens were successfully genotyped with a median turnaround time of 31 days
      (range, 9-155). Of the 344 specimens, 185 (54%) had at least one identifiable
      somatic alteration (KRAS: 24%, EGFR: 17%, ALK: 5%, BRAF: 5%, HER2: 4%, PIK3CA:
      2%). As of August 1, 2011, 63 of 288 advanced NSCLC patients (22%) had received
      molecularly targeted therapy based on their genotypic results, including 34 of 42
      patients (81%) with EGFR mutations, 12 of 15 (80%) with ALK rearrangements, and
      17 of 95 (18%) with KRAS, BRAF, or HER2 mutations. CONCLUSIONS: Large-scale
      testing for somatic alterations in EGFR, KRAS, BRAF, PIK3CA, HER2, and ALK is
      feasible and impacts therapeutic decisions. As the repertoire for personalized
      therapies expands in lung cancer and other malignancies, there is a need to
      develop new genomics technologies that can generate a comprehensive genetic
      profile of tumor specimens in a time- and cost-effective manner.

PMID- 23154548
TI  - FGFR1 amplification in squamous cell carcinoma of the lung.
AB  - INTRODUCTION: Amplification of fibroblast growth factor receptor 1 (FGFR1) has
      been reported in squamous cell lung carcinoma and may be a molecular target for
      therapy. Little is known, however, about the clinical and demographic correlates
      of FGFR1 amplification. METHODS: The study is an Institutional Review Board
      approved retrospective analysis of 226 patients with squamous cell lung cancer
      seen at the Massachusetts General Hospital from 2005 to 2011. Clinical and
      demographic characteristics of all patients were obtained, as well as treatment
      details including surgery, radiation, and chemotherapy, and overall survival.
      fluorescence in situ hybridization was performed for FGFR1 on formalin-fixed
      paraffin-embedded tumor tissue. Clinical genotyping results were also reviewed
      where available. RESULTS: Thirty-seven of 226 patients (16%) with squamous cell
      lung cancer were found positive for amplification using a definition of
      amplification of a gene to copy number control ratio of 2.2 or higher. FGFR1
      amplification status was not associated with age, sex, stage, histologic subtype
      within squamous cell, smoking history, or pack-years of smoking. We found no
      significant difference in overall survival by FGFR1 amplification status as a
      whole; in the advanced stage subset, our findings are inconclusive because of the
      small sample size. CONCLUSION: FGFR1 amplification was found in 16% of a clinical
      cohort of squamous cell lung cancer patients. The lack of any specific
      clinicodemographic features that correlates with FGFR1 amplification suggests
      that all squamous cell patients should be tested for this genomic change.

PMID- 23154549
TI  - Can determination of circulating endothelial cells and serum caspase-cleaved CK18
      predict for response and survival in patients with advanced non-small-cell lung
      cancer receiving endostatin and paclitaxel-carboplatin chemotherapy? a
      retrospective study.
AB  - INTRODUCTION: Early prediction of the efficacy of a combination of an
      antiangiogenic drug with cytotoxic chemotherapy is a significant challenge. In
      that regard, circulating endothelial cells (CECs) and cytokeratins (CKs) seem to
      reflect their roles in both tumor angiogenesis and tumor cell death. METHODS:
      Patients with advanced, previously untreated non-small-cell lung cancer were
      randomly assigned to an endostatin treatment group (paclitaxel + carboplatin +
      endostatin) and a control group (paclitaxel + carboplatin + placebo). A total of
      122 patients were evaluated, of whom 107 had measurements of blood CECs, CK8,
      caspase-cleaved CK18 (ccCK18), and uncleaved CK18 (CK18) before and at weeks 3
      and 6 of treatment, respectively. RESULTS: Higher baseline CECs in patients with
      a tumor response (partial remission + stable disease, p = 0.002 for the entire
      group; p = 0.000 for the treatment group) were observed. The number of CECs
      decreased significantly after endostatin treatment (p = 0.000), whereas CK levels
      increased. Increased levels of ccCK18 and CK18, but not CK8, reached significance
      (p = 0.001 and p = 0.048, respectively) when compared with the baseline. Tumor
      response showed a strong correlation with reduction of CECs (p = 0.000) and
      increase of ccCK18 (p = 0.040) after endostatin therapy. Cutoff values of changes
      of CECs and ccCK18 for prediction of survival were 0.58/MUl and 19.6 ng/ml,
      respectively. Reduction of CECs and increase of ccCK18 significantly correlated
      with longer median survival (p = 0.013 and p = 0.016 for progression-free
      survival; p = 0.009 and p = 0.012 for overall survival, respectively).
      CONCLUSIONS: CECs and CKs could be biomarkers for selecting patients with non
      small-cell lung cancer who will benefit from treatment with endostatin in
      combination with paclitaxel plus carboplatin.

PMID- 23154550
TI  - Prognostic impact of CD204-positive macrophages in lung squamous cell carcinoma:
      possible contribution of Cd204-positive macrophages to the tumor-promoting
      microenvironment.
AB  - INTRODUCTION: Tumor-associated macrophages (TAMs) are recruited into cancer
      induced stroma and produce a specific microenvironment for cancer progression.
      CD204 (+) TAMs are reportedly related to tumor progression and clinical outcome
      in some tumors. The aim of this study was to clarify the correlation between
      CD204 (+) TAMs and the clinicopathological features of lung squamous cell
      carcinoma. METHODS: We investigated the relationships between the numbers of
      CD204 (+) TAMs and clinicopathological factors, microvessel density, and the
      numbers of Foxp3 (+) lymphocytes in 208 consecutively resected cases. We also
      examined the relationships between the numbers of CD204 (+) TAMs and the
      expression levels of cytokines involved in the migration and differentiation of
      CD204 (+) TAMs. RESULTS: A high number of CD204 (+) TAMs in the stroma was
      significantly correlated with an advanced p-stage, T factor, N factor, and the
      presence of vascular and pleural invasion. A high number of CD204 (+) TAMs in the
      stroma was also a significant prognostic factor for all p-stages and p-stage I.
      Moreover, the numbers of CD204 (+) TAMs were correlated with the microvessel
      density and the numbers of Foxp3 (+) lymphocytes. A high number of CD204 (+) TAMs
      was strongly correlated with the tissue expression level of monocyte
      chemoattractant protein-1. CD204 (+) TAMs were shown to be significant
      independent prognostic factors in a multivariate analysis. CONCLUSIONS: CD204 (+)
      TAMs were an independent prognostic factor in lung squamous cell carcinoma. CD204
      (+) TAMs, along with other tumor-promoting stromal cells such as regulatory T
      cells and endothelial cells, may create tumor-promoting microenvironments.

PMID- 23154551
TI  - Mediastinal lymph node examination and survival in resected early-stage non-small
      cell lung cancer in the surveillance, epidemiology, and end results database.
AB  - BACKGROUND: Pathologic nodal stage is the key prognostic factor in resectable non
      small-cell lung cancer (NSCLC). Mediastinal lymph node (MLN) metastasis connotes
      a poor prognosis. Yet, some NSCLC resections exclude MLN examination. METHODS: We
      analyzed U.S. Surveillance, Epidemiology, and End Results program data from 1998
      to 2002 to quantify the long-term survival impact of failure to examine MLN in
      resected NSCLC. We used Kaplan-Meier methods to compare the unadjusted survival
      difference between patients with, and without, MLN examination, and Cox
      proportional hazards and competing risk models to serially adjust for the impact
      of risk factors on survival differences. RESULTS: Sixty-two percent of patients
      with pathologic N0 or N1 NSCLC had no MLN examined. Overall 5-year survival rates
      were 52% for those with, versus 47% for those without, MLN examination; lung
      cancer-specific survival rates were 63% versus 58% respectively (p < 0.001);
      nonlung cancer mortality was identical between cohorts. Adjusting for potential
      confounders, MLN examination was associated with a 7% reduction in all-cause
      mortality (hazard ratio, 0.93; confidence interval, 0.88-0.97; p = 0.002), and
      11% reduction in lung cancer-specific mortality (hazard ratio, 0.89; 95%
      confidence interval, 0.84-0.95; p < 0.001) rates. The excess risk in 1 year's
      cohort of U.S. lung resections was 3150 lives over 5 years. CONCLUSIONS: Failure
      to examine MLN was a common practice in MLN-negative NSCLC resections, which
      significantly impaired long-term survival. Efforts to understand the etiology of
      this quality gap, and measures to eliminate it, are warranted.

PMID- 23154553
TI  - Distinct clinical course of EGFR-mutant resected lung cancers: results of testing
      of 1118 surgical specimens and effects of adjuvant gefitinib and erlotinib.
AB  - BACKGROUND: EGFR and KRAS mutations are mutually exclusive and predict outcomes
      with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI)
      treatment in patients with stage IV lung cancers. The clinical significance of
      these mutations in patients with resected stage I-III lung cancers is unclear.
      METHODS: At our institution, resection specimens from patients with stage I-III
      lung adenocarcinomas are tested for the presence of EGFR or KRAS mutations during
      routine pathology analysis such that the results are available before
      consideration of adjuvant therapy. In a cohort of 1118 patients tested over 8
      years, overall survival was analyzed using multivariate analysis to control for
      potential confounders, including age, sex, stage, and smoking history. The impact
      of adjuvant erlotinib or gefitinib was examined in an independent data set of
      patients exclusively with EGFR mutation, in which date of recurrence was
      recorded. RESULTS: In the overall population, we identified 227 KRAS (25%) and
      222 EGFR (20%) mutations. Patients with EGFR-mutant lung cancers had a lower risk
      of death compared with those without EGFR mutations, overall survival (OS) HR
      0.51 (95% confidence interval [CI]: 0.34-0.76, p < 0.001). Patients with KRAS
      mutant lung cancers had similar outcomes compared with individuals with KRAS wild
      type tumors, OS HR 1.17 (95% CI: 0.87-1.57, p = 0.30). A separate data set
      includes only patients with EGFR-mutant lung cancers identified over 10 years (n
      = 286). In patients with resected lung cancers and EGFR mutation, treatment with
      adjuvant erlotinib or gefitinib was associated with a lower risk of recurrence or
      death, disease-free survival HR 0.43 (95% CI: 0.26-0.72, p = 0.001), and a trend
      toward improved OS. CONCLUSIONS: Patients with resected stage I-III lung cancers
      and EGFR mutation have a lower risk of death compared with patients without EGFR
      mutation. This may be because of treatment with EGFR TKIs. Patients with, and
      without KRAS mutation have similar OS. These data support reflex testing of
      resected lung adenocarcinomas for EGFR mutation to provide prognostic information
      and identify patients for enrollment on prospective clinical trials of adjuvant
      EGFR TKIs.

PMID- 23154554
TI  - Overall survival improvement in patients with lung cancer and bone metastases
      treated with denosumab versus zoledronic acid: subgroup analysis from a
      randomized phase 3 study.
AB  - INTRODUCTION: Denosumab, a fully human anti-RANKL monoclonal antibody, reduces
      the incidence of skeletal-related events in patients with bone metastases from
      solid tumors. We present survival data for the subset of patients with lung
      cancer, participating in the phase 3 trial of denosumab versus zoledronic acid
      (ZA) in the treatment of bone metastases from solid tumors (except breast or
      prostate) or multiple myeloma. METHODS: Patients were randomized 1:1 to receive
      monthly subcutaneous denosumab 120 mg or intravenous ZA 4 mg. An exploratory
      analysis, using Kaplan-Meier estimates and proportional hazards models, was
      performed for overall survival among patients with non-small-cell lung cancer
      (NSCLC) and SCLC. RESULTS: Denosumab was associated with improved median overall
      survival versus ZA in 811 patients with any lung cancer (8.9 versus 7.7 months;
      hazard ratio [HR] 0.80) and in 702 patients with NSCLC (9.5 versus 8.0 months; HR
      0.78) (p = 0.01, each comparison). Further analysis of NSCLC by histological type
      showed a median survival of 8.6 months for denosumab versus 6.4 months for ZA in
      patients with squamous cell carcinoma (HR 0.68; p = 0.035). Incidence of overall
      adverse events was balanced between treatment groups; serious adverse events
      occurred in 66.0% of denosumab-treated patients and 72.9% of ZA-treated patients.
      Cumulative incidence of osteonecrosis of the jaw was similar between groups (0.7%
      denosumab versus 0.8% ZA). Hypocalcemia rates were 8.6% with denosumab and 3.8%
      with ZA. CONCLUSION: In this exploratory analysis, denosumab was associated with
      improved overall survival compared with ZA, in patients with metastatic lung
      cancer.

PMID- 23154552
TI  - Local ablative therapy of oligoprogressive disease prolongs disease control by
      tyrosine kinase inhibitors in oncogene-addicted non-small-cell lung cancer.
AB  - INTRODUCTION: Many patients with oncogene-driven non-small-cell lung cancer
      (NSCLC) treated with tyrosine kinase inhibitors experience limited sites of
      disease progression. This study investigated retrospectively the benefits of
      local ablative therapy (LAT) to central nervous system (CNS) and/or limited
      systemic disease progression and continuation of crizotinib or erlotinib in
      patients with metastatic ALK gene rearrangement (ALK+) or EGFR-mutant (EGFR-MT)
      NSCLC, respectively. METHODS: Patients with metastatic ALK+ NSCLC treated with
      crizotinib (n = 38) and EGFR-MT NSCLC treated with erlotinib (n = 27) were
      identified at a single institution. Initial response to the respective kinase
      inhibitors, median progression-free survival (PFS1), and site of first
      progression were recorded. A subset of patients with either nonleptomeningeal CNS
      and/or four sites or fewer of extra-CNS progression (oligoprogressive disease)
      suitable for LAT received either radiation or surgery to these sites and
      continued on the same tyrosine kinase inhibitors. The subsequent median
      progression-free survival from the time of first progression (PFS2) and pattern
      of progression were recorded. RESULTS: Median progression-free survival in ALK+
      patients on crizotinib was 9.0 months, and 13.8 months for EGFR-MT patients on
      erlotinib. Twenty-five of 51 patients (49%) who progressed were deemed suitable
      for local therapy (15 ALK+, 10 EGFR-MT; 24 with radiotherapy, one with surgery)
      and continuation of the same targeted therapy. Post-LAT, 19 of 25 patients
      progressed again, with median PFS2 of 6.2 months. DISCUSSION: Oncogene-addicted
      NSCLC with CNS and/or limited systemic disease progression (oligoprogressive
      disease) on relevant targeted therapies is often suitable for LAT and
      continuation of the targeted agent, and is associated with more than 6 months of
      additional disease control.

PMID- 23154555
TI  - Quality of life analysis of TORCH, a randomized trial testing first-line
      erlotinib followed by second-line cisplatin/gemcitabine chemotherapy in advanced
      non-small-cell lung cancer.
AB  - INTRODUCTION: The TORCH (Tarceva or Chemotherapy) trial randomized patients with
      advanced non-small-cell lung cancer to first-line erlotinib followed by second
      line cisplatin/gemcitabine versus. standard inverse sequence. The trial, designed
      to test noninferiority in overall survival, was stopped at interim analysis
      because of inferior survival in the experimental arm. Quality of life (QoL), a
      secondary outcome, is reported here. METHODS: QoL was assessed at baseline and
      every 3 weeks during first-line, using European Organization for Research and
      Treatment of Cancer Quality of Life Questionnaire - Core 30 and QLQ-lung cancer
      specific module (LC13). Mean changes from baseline within arms were reported. QoL
      response and time-to-deterioration of QoL using a competing-risk approach were
      compared between treatment arms. RESULTS: Six hundred and thirty patients (83%)
      completed baseline questionnaires. Compliance was affected by differential
      treatment efficacy, but was similar between arms for patients without progression
      or death. Significant differences in QoL responses were observed favoring
      chemotherapy for pain, sleeping, dyspnea, diarrhea, and favoring erlotinib for
      vomiting, constipation, sore mouth, and alopecia. In the small subset of patients
      with EGFR-mutated tumors, all selected items (global QoL, physical functioning,
      cough, dyspnea and pain) improved, whereas worsening or no change was observed in
      wild-type patients. Improvement was particularly evident in the first-line
      erlotinib arm as for global QoL and physical functioning. CONCLUSIONS: QoL was
      impacted by differential toxicity and efficacy between arms. Functional domains
      and global QoL did not differ, although some symptoms were better controlled with
      chemotherapy in unselected non-small-cell lung cancer patients.

PMID- 23154556
TI  - E1B-55 kDa-defective adenoviruses activate p53 in mesothelioma and enhance
      cytotoxicity of anticancer agents.
AB  - INTRODUCTION: Genetic characterization of malignant mesothelioma shows a
      homozygous deletion of the INK4A/ARF locus, which results in inactivation of the
      p53 pathways. METHODS: We examined possible antitumor effects of adenoviruses
      with a deletion of the E1B-55kD gene (Ad-delE1B55) on mesothelioma and
      investigated combinatory actions with the first-line chemotherapeutic agents.
      RESULTS: Ad-delE1B55 produced cytotoxicity on mesothelioma cells, which was
      associated with p53 phosphorylation, pRb dephosphorylation, and cleavage of
      caspases. Ad-delE1B55-infected cells displayed hyperploidy at the cell-cycle
      analysis and showed enlarged nuclear configurations. Combination of Ad-delE1B55
      plus cisplatin or pemetrexed produced antitumor effects in vitro. Furthermore, Ad
      delE1B55 and cisplatin showed combinatory effects in an orthotopic animal model.
      CONCLUSIONS: Cell death caused by Ad-delE1B55 is attributable to cell-cycle
      arrest at M-phase checkpoint followed by activated apoptotic pathways, and
      combination of the first-line chemotherapeutic agents and the oncolytic
      adenovirus is a potential therapeutic for mesothelioma.

PMID- 23154557
TI  - Incidence and survival of malignant pleural mesothelioma in norway: a population
      based study of 1686 cases.
AB  - BACKGROUND: Asbestos-related malignant pleural mesothelioma is one of the most
      lethal tumor types. The advent of antimetabolite treatment as pemetrexed,
      introduced in the early 2000s, may have increased survival on a population basis.
      In this study, we have analyzed population-based incidence and survival data over
      the last 40 years. METHODS: Complete national data on 1686 patients from the
      Cancer Registry of Norway sampled from 1970 to 2009 are presented, with incidence
      rates in 5-year periods. Relative survival for 1 year and 3 years and median
      survival in 5-year intervals were calculated. RESULTS: The incidence of malignant
      pleural mesothelioma has been significantly and steadily increasing from 1970
      until 2009, with 50 patients diagnosed in the period 1970-1974 and 377 diagnosed
      in 2005-2009. The incidence was highest among men in all time periods. A slight
      decline was observed in the last period. The 1-year survival rate increased from
      20.7% to 44.0% during the period 1970-2009, whereas the 3-year survival rate
      remained below 10%. Median survival increased from 4.0 months in the first period
      to 9.3 months in the last period. CONCLUSIONS: The incidence of malignant pleural
      mesothelioma follows the curve of asbestos exposure with a 20- to 40-year lag.
      There has been a significant increase in survival, most likely because of earlier
      diagnosis and improvements in cytostatic treatment.

PMID- 23154558
TI  - Tomotherapy after pleurectomy/decortication or biopsy for malignant pleural
      mesothelioma allows the delivery of high dose of radiation in patients with
      intact lung.
AB  - INTRODUCTION: This study aimed to assess the safety of high doses of radiation
      delivered with tomotherapy to the intact lung after radical
      pleurectomy/decortication or biopsy for malignant pleural mesothelioma (MPM).
      METHODS: Twenty-eight patients were enrolled in this prospective study and
      underwent adjuvant or definitive tomotherapy after radical
      pleurectomy/decortication (n = 20) or pleural biopsy (n = 8) for MPM. The dose
      prescribed to the planning target volume, defined as the entire hemithorax,
      including chest-wall incisions and drain sites and excluding the intact lung, was
      50 Gy delivered in 25 fractions. All patients underwent fluorodeoxyglucose
      positron emission tomography for staging after surgery. Any fluorodeoxyglucose
      avid areas or regions of particular concern for residual disease were given a
      simultaneous boost of radiotherapy to 60 Gy. Specific lung dosimetric parameters
      were reported. Toxicity was graded using the modified Common Toxicity Criteria
      version 3.0. RESULTS: The median follow-up was of 19 months (range, 6-29 months).
      Five patients (17.8%) experienced severe respiratory symptoms corresponding to
      grade 2 pneumonitis in three cases, and grade 3 pneumonitis in two cases. No
      fatal respiratory toxicity was reported. Controlateral lung V5 was strongly
      correlated with the risk of pneumonitis. Patients who developed grade 2 and 3
      pneumonitis had a higher controlateral lung V5 (mean V5=32%) than those without
      pneumonitis (mean V5=17%) (p=0.002). Other two grade 3 toxicities were
      registered: one severe pain to the chest wall, and one severe thrombocytopenia.
      CONCLUSIONS: Tomotherapy allows the safe delivery of high dose of radiation to
      the hemithorax of MPM patients with intact lung.

PMID- 23154559
TI  - Thymoma-a clinico-pathological long-term study with emphasis on histology and
      adjuvant radiotherapy dose.
AB  - INTRODUCTION: To evaluate prognostic factors of thymic epithelial tumors (TETs)
      with particular reference to histology and the dose-response relationship of
      adjuvant radiotherapy. METHODS: Retrospective study with central pathological
      review on patients resected for TET between 1966 and 2004 at a single
      institution. Prognostic factors were identified using Cox regression analysis.
      RESULTS: From 93 patients with TET, 33.3% relapsed and 47.3% died. Cause of death
      was known in 64% and attributed to TET in 25%. Myasthenia gravis was associated
      with superior disease-free survival (DFS) and overall survival (OS). Tumors
      smaller than 8.5 cm had a significantly better prognosis. With a median follow-up
      of 9.8 years actuarial OS at 5, 10, and 20 years were 96%, 92%, and 47% in stage
      I; 85%, 61%, and 53% in stage II; 72%, 39%, and 15% in stage III and IV. Advanced
      stage and incomplete resection had a negative impact on DFS and OS. According to
      histology (WHO type A, AB, B1; favorable; versus WHO type B2, B3; intermediate;
      versus thymic carcinoma, unfavorable) three prognostic groups were discernible.
      On multivariate analysis, tumor size, and stage emerged as prognostic factors,
      but neither histology nor myasthenia. Postoperative radiotherapy was administered
      in 27 patients (median dose 50.8 Gy). Doses in excess of 50 Gy were associated
      with significantly improved DFS and OS. CONCLUSIONS: Tumor stage, histology,
      complete resection, and tumor size had a significant impact on survival.
      Myasthenia may facilitate early detection and is correlated with superior
      survival. When postoperative radiotherapy is administered, doses above 50 Gy may
      improve outcome.

PMID- 23154560
TI  - Identification of CCDC6-RET fusion in the human lung adenocarcinoma cell line, LC
      2/ad.
AB  - Rearranged during transfection (RET) fusions have been newly identified in
      approximately 1% of patients with primary lung tumors. However, patient-derived
      lung cancer cell lines harboring RET fusions have not yet been established or
      identified, and therefore, the effectiveness of an RET inhibitor on lung tumors
      with endogenous RET fusion has not yet been studied. In this study, we report
      identification of CCDC6-RET fusion in the human lung adenocarcinoma cell line LC
      2/ad. LC-2/ad showed distinctive sensitivity to the RET inhibitor, vandetanib,
      among 39 non-small lung cancer cell lines. The xenograft tumor of LC-2/ad showed
      cribriform acinar structures, a morphologic feature of primary RET fusion
      positive lung adenocarcinomas. LC-2/ad cells could provide useful resources to
      analyze molecular functions of RET-fusion protein and its response to RET
      inhibitors.

PMID- 23154561
TI  - Giant sternal condrosarcoma.

PMID- 23154562
TI  - The cancer stem-cell hypothesis: its emerging role in lung cancer biology and its
      relevance for future therapy.
AB  - The cancer stem-cell (CSC) hypothesis suggests that there is a small subset of
      cancer cells that are responsible for tumor initiation and growth, possessing
      properties such as indefinite self-renewal, slow replication, intrinsic
      resistance to chemotherapy and radiotherapy, and an ability to give rise to
      differentiated progeny. Through the use of xenotransplantation assays, putative
      CSCs have been identified in many cancers, often identified by markers usually
      expressed in normal stem cells. This is also the case in lung cancer, and the
      accumulated data on side population cells, CD133, CD166, CD44 and ALDH1 are
      beginning to clarify the true phenotype of the lung cancer stem cell.
      Furthermore, it is now clear that many of the pathways of normal stem cells,
      which guide cellular proliferation, differentiation, and apoptosis are also
      prominent in CSCs; the Hedgehog (Hh), Notch, and Wnt signaling pathways being
      notable examples. The CSC hypothesis suggests that there is a small reservoir of
      cells within the tumor, which are resistant to many standard therapies, and can
      give rise to new tumors in the form of metastases or relapses after apparent
      tumor regression. Therapeutic interventions that target CSC pathways are still in
      their infancy and clinical data of their efficacy remain limited. However
      Smoothened inhibitors, gamma-secretase inhibitors, anti-DLL4 antagonists, Wnt
      antagonists, and CBP/beta-catenin inhibitors have all shown promising anticancer
      effects in early studies. The evidence to support the emerging picture of a lung
      cancer CSC phenotype and the development of novel therapeutic strategies to
      target CSCs are described in this review.

PMID- 23154563
TI  - Intravascular lymphoma as a cause of respiratory failure.

PMID- 23154564
TI  - A dramatic response to crizotinib in a non-small-cell lung cancer patient with
      IHC-positive and FISH-negative ALK.

PMID- 23154565
TI  - First case of combined small-cell lung cancer with adenocarcinoma harboring EML4
      ALK fusion and an exon 19 EGFR mutation in each histological component.

PMID- 23154566
TI  - Adopting integrated care pathways in non-small-cell lung cancer.

PMID- 23154567
TI  - Antibody independent microfluidic cell capture of circulating tumor cells for the
      diagnosis of cancer.

PMID- 23154568
TI  - Oncogenic fusions involving exon 19 of ALK.

PMID- 23154570
TI  - A phase I study of concurrent external beam radiotherapy with weekly topotecan
      for primary treatment of locally advanced lung cancers.

PMID- 23154571
TI  - Unexpected doxorubicin-mediated cardiotoxicity in sisters: possible role of
      polymorphisms in histamine n-methyl transferase.
AB  - The anthracycline anticancer agent doxorubicin has long been recognized to induce
      a dose-limiting cardiotoxicity and may be associated with genes relevant to
      doxorubicin disposition. Recent reports suggest a role for a number of single
      nucleotide polymorphisms in anthracycline cardiotoxicity in children. We describe
      two adult sisters with anthracycline cardiotoxicity that developed after a
      relatively low dose of doxorubicin. One sister carried the variant genotype for
      histamine N-ethyl transferase (HNMT, rs17583889) while the other was
      heterozygous, suggesting a similar role for these genotypes in adults with
      anthracycline cardiotoxicity. Although this requires further study, these
      genotypes may be important in the clinical dosing, or use of the liposomal
      formulation of doxorubicin. 

PMID- 23154572
TI  - Severe infusion reactions to brentuximab vedotin in two patients with Hodgkin
      lymphoma previously treated with allogeneic stem cell transplantation.
AB  - Brentuximab vendotin is a monoclonal antibody approved in August 2011 for use in
      patients with Hodgkin disease and a rare systemic lymphoma known as anaplastic
      large cell lymphoma. Brentuximab is approved in patients with Hodgkin disease who
      have failed autologous transplantation or after failure of at least two prior
      multi-agent chemotherapy regimens but has not been studied following allogeneic
      transplantation. Four patients with relapsed Hodgkin disease have been treated at
      our institution with at least two doses of brentuximab vendotin. Two patients
      have experienced significant infusion reactions on multiple occasions, and two
      patients have tolerated the infusions well. During phase 2 trials, there were no
      reports of Grade 3 or 4 infusion-related reactions. Both patients with reactions
      had relapsed following allogeneic stem cell transplants, while neither of the
      patients who tolerated the infusions had undergone transplantation. We report our
      experience with brentuximab vendotin-treated patients at our institution,
      focusing on the two post-allogeneic patients who experienced multiple significant
      infusion reactions. This report evaluates possible mechanisms behind their
      reactions, including previous allogeneic stem cell transplantation as a likely
      precipitating factor. 

PMID- 23154573
TI  - Successful treatment of nilotinib-induced pleural effusion with prednisone.
AB  - Chronic myeloid leukemia is characterized by a unique reciprocal translocation
      between chromosomes 9 and 22 resulting in deregulated tyrosine kinase activity.
      Tyrosine kinase inhibitors, such as imatinib, dasatinib, and nilotinib have
      revolutionized treatment of Chronic myeloid leukemia. However, tyrosine kinase
      inhibitors' use has presented new challenges in managing both acute and chronic
      toxicities, particularly 'off-target' toxicities like pleural effusion. Pleural
      effusions are seen less often with imatinib and very rarely with nilotinib. A 66
      year-old male presented to emergency department with complaints of mild chest
      pain and dyspnea of 3 days duration with progressive worsening, including dyspnea
      at rest. Patient was currently taking nilotinib after failing imatinib for
      chronic myeloid leukemia. Nilotinib was put on hold. After exclusion of cardiac
      and pulmonary etiologies patient was treated for community acquired pneumonia
      with minimal improvement. Despite the very low incidence of pleural effusion with
      nilotinib (<1%), he was started on 20 mg of prednisone PO for 3 days. Patient had
      a dramatic improvement within 48 h after beginning prednisone. This treatment
      approach suggests that pleural effusions associated with nilotinib can be
      successfully treated in the same way as pleural effusions associated with
      dasatinib.

PMID- 23154574
TI  - Cetuximab infusion reactions: French pharmacovigilance database analysis.
AB  - OBJECTIVES: To compare characteristics of patients exhibiting cetuximab infusion
      reactions or another adverse drug reaction related to cetuximab and to identify
      factors associated with the severity of cetuximab infusion reactions. METHODS:
      All cases of adverse drug reaction reported with cetuximab from 1985 to 2010 were
      extracted from the French Pharmacovigilance database. The severity of infusion
      reactions was assessed according to the NCI-CTCAE criteria (v4.0). Multiple
      logistic regression analysis was performed to identify factors associated with
      the severity of infusion reactions. RESULTS: Among the 602 adverse drug reaction
      reported with cetuximab during the study period, 374 infusion reactions were
      identified. Indication is more likely to be head and neck than colorectal cancer
      among patients experiencing an infusion reaction (p < 0.001). Among the seven
      deaths related to an infusion reaction, five patients were treated for head and
      neck cancer. Infusion reactions were more likely to be severe when they occurred
      during the first administration (OR = 7.40 95% CI [2.21-24.71]), adjusted for
      age, sex, region of France, quarter of the year, indication, year of occurrence,
      and premedication. CONCLUSION: Our study found that reports of infusion reactions
      more often concerned patients treated for head and neck cancer, that in these
      patients the adverse drug reaction was more often fatal and severe infusion
      reactions were more likely during the first administration. In daily practice,
      the close monitoring of patients during the first infusion, especially patients
      with head and neck cancer, is recommended. Considering the possible
      immunoglobulin E-mediated mechanism, reliable tests for their detection need to
      be readily available.

PMID- 23154575
TI  - Plaque-stabilizing effect of angiotensin-converting enzyme inhibitor and/or
      angiotensin receptor blocker in a rabbit plaque model.
AB  - AIM: Previous studies have revealed that blockade of the renin angiotensin system
      attenuates plaque vulnerability and reduces cardiovascular events; however, few
      studies have compared the effects of an angiotensin-converting enzyme inhibitor
      (ACEI) with an angiotensin receptor blocker (ARB) and evaluated combination
      therapy. The objective of this study was to compare the efficacy and mechanisms
      of plaque stabilization by ACEI or ARB and to determine the effects of
      combination therapy. METHODS: Twenty-eight male Japanese white rabbits were fed a
      high-cholesterol diet after balloon injury of the carotid arteries, then
      separated into ACEI (n= 7; imidapril 0.5 mg/kg/day), ARB (n= 7; TA606 4.5
      mg/kg/day), combination (n= 7; imidapril 0.5 mg/kg/day+TA606 4.5 mg/kg/day), and
      vehicle (n= 7) groups. RESULTS: No difference in plaque volume was identified
      among the 4 groups. ACEI or ARB increased the thickness of the fibrous cap,
      collagen content and the number of smooth muscle cells in the intima (% smooth
      muscle cell in intima: ACEI, 36.3%; ARB, 36.4%; vehicle, 14.9%), and reduced the
      accumulation of macrophages (% macrophages in intima: ACEI, 20.1%; ARB, 24.0%;
      vehicle, 37.9%), suggesting the plaque-stabilizing effects of each drug. ACEI
      reduced matrix metalloproteinase (MMP)-9 expression and gelatinolytic activity in
      the intima. While ARB did not change gelatinolytic activity, accumulation ot T
      cell in the intima was suppressed. Combination therapy did not show additive
      effects. CONCLUSION: These results suggest that ACEIs and ARBs have similar, but
      not additive, plaque-stabilizing effects. Each agent showed specific effects,
      with ACEIs decreasing gelatinolytic activity and ARBs suppressing T cell
      accumulation.

PMID- 23154576
TI  - High prevalence of normal waist circumference in Japanese employees with a
      cluster of metabolic abnormalities.

PMID- 23154577
TI  - Acute effects of postprandial aerobic exercise on glucose and lipoprotein
      metabolism in healthy young women.
AB  - AIM: To investigate the acute effects of postprandial exercise on glucose and
      lipoprotein metabolism after the intake of glucose with or without fat cream in
      healthy but sedentary young women. METHODS: Healthy young Japanese women with a
      sedentary lifestyle, normal weight (18.5<=BMI<25), normal ovarian cycle, and
      apolipoprotein (apo) E3/3 were enrolled as participants. They ingested 1 g/kg
      body weight of glucose only or glucose supplemented with 1 g/kg oral fat
      tolerance test (OFTT) cream 4 (0.35 g/kg as fat) with or without postprandial
      walking exercise on a motorized treadmill (ca. 50%V(.)o(2)max for 30 min) 20 min
      after intake of the beverage. Each subject performed 4 trials in a randomized,
      cross-over design. Venous blood was drawn before (0 h), and 20 min, 1, 2, 4, and
      6 h after ingestion. RESULTS: Postprandial exercise alleviated the sharp rise of
      serum glucose and insulin, and transiently mitigated the decrease of free fatty
      acids (FFA) after ingestion of the glucose-only beverage. Although no fat was
      contained in the glucose beverage, transient apoB48 secretion was observed
      without the rise of serum triglyceride (TG) and remnant-like particle (RLP)-TG,
      suggesting that apoB48-containing lipoprotein particles with little TG were
      released by the exercise. Serum apoB48 concentrations at 6 h had decreased to
      levels lower than the baseline (0 h, after 12-h overnight fast) with or without
      exercise, suggesting that the 12-h overnight fast may not have been a 'true'
      fast. Similarly, postprandial exercise suppressed the sharp rise of serum glucose
      and insulin, and transiently mitigated the decrease of FFA after the ingestion of
      glucose with OFTT cream. Postprandial exercise stimulated the transient secretion
      of apoB48-containing TG-rich lipoproteins (TRL) with a rapid rise of serum
      apoB48, TG, and RLP-TG; however, the subsequent course of lipemia was not
      significantly changed. Serum apoB48 and RLP-TG values did not return to the
      baseline even after 6 h, suggesting that postprandial lipoprotein metabolism was
      not finished at the end of the experiment. CONCLUSION: Postprandial aerobic
      exercise alleviated the glycemic peak at 1 h associated with insulin 'sparing'.
      The effect of exercise on fat metabolism was transient, enhancing the secretion
      of intestinal TRL at an early phase, but no further significant effects were
      observed. Postprandial exercise transiently stimulated the secretion of apoB48
      after glucose intake without a fat load.

PMID- 23154578
TI  - Effects of lutein supplement on serum inflammatory cytokines, ApoE and lipid
      profiles in early atherosclerosis population.
AB  - AIM: The purpose of this study was to determine the effects of lutein supplement
      on serum cytokines, apoE and lipoprotein profiles in early atherosclerosis
      population. METHODS: Early atherosclerosis patients (n= 65) were randomized to
      receive placebo (A+P, n= 31) or 20 mg/d lutein (A+L, n= 34) for 3 months.
      RESULTS: Serum lutein increased significantly compared to baseline after lutein
      supplements in A+L group (p<0.001). Lutein supplements resulted in a significant
      decrease in serum interleukin-6 (IL-6) and monocyte chemoattractant protein-1
      (MCP-1) at 3 month in A+L group (p<0.05). Intragroup comparison revealed a
      significant difference in the changes of serum MCP-1 between A+L and A+P groups
      (p= 0.021). The serum low-density lipoprotein (LDL) and triglyceride (TG)
      significantly decreased in A+L group (p<0.05). The changes in serum lutein were
      negatively associated with those in serum LDL in A+L group (r=-0.384, p=0.043),
      while no such relationship was observed in A+P group (r= 0.087, p= 0.685).
      CONCLUSION: An increase in serum lutein after supplementation can reduce
      inflammatory cytokines and regulate serum lipids, which may pay important roles
      in early atherosclerosis.

PMID- 23154579
TI  - An optimum projection and noise reduction approach for detecting rare and common
      variants associated with complex diseases.
AB  - BACKGROUND: Despite the thrilling advances in identifying gene variants that
      influence common diseases, most of the heritable risk for many common diseases
      still remains unidentified. One of the possible reasons for this missing
      heritability is that the genome-wide association study (GWAS) approaches have
      been focusing on common rather than rare single nucleotide variants (SNVs).
      Consequently, there is currently a great deal of interest in developing methods
      that can interrogate rare variants for association with diseases. METHODS: We
      propose a two-step method (termed rPLS) to reveal possible genetic effects
      related to rare as well as common variants. The procedure starts with removing
      irrelevant variants using penalized regression (regularization) which is followed
      by partial least squares (PLS) on the surviving SNVs to find an optimal linear
      combination of rare and common SNVs within a genomic region that is tested for
      its association with the trait of interest. RESULTS: Simulation settings based on
      the 1000 Genomes sequencing data and reflecting real situations demonstrated that
      rPLS performs well compared to existing methods especially when there are a large
      number of noncausal variants (both rare and common) present in the gene and when
      causal SNVs have different effect sizes and directions.

PMID- 23154581
TI  - Modeling problem-oriented clinical notes.
AB  - OBJECTIVES: To develop a model as a starting-point for developing a problem
      oriented clinical notes application as a generic component of an Electronic
      Health Record (EHR). METHODS: We used the generic conceptualization of Weed's
      problem-oriented medical record (POMR) to link progress notes to problems, and
      the Subjective, Objective, Assessment, Plan (SOAP) headings to classify elements
      of these notes. Health Level 7 (HL7) Version 3 and Unified Modeling Language
      (UML) were used for modeling. We looked especially at the role of Conditions and
      Concerns, and how to model these to document clinical reasoning. RESULTS: We
      developed a generic HL7-based model for progress notes. In this model the
      specific clinical note has a condition as its reason. An assertion can be made
      about a condition. Any condition, observation or procedure can be a concern that
      has to be tracked. Utmost important is the relationship between constituting
      parts of a progress note and specially between progress notes by linking a
      progress note to conditions that are part of an earlier progress note. From this
      model a comprehensive hierarchical condition tree can be built. Several views,
      such as chronological, SOAP and condition-oriented, are possible. The clinical
      notes application is used in daily clinical practice. The model meets explicit
      design criteria and clinical needs. CONCLUSIONS: With the comprehensive HL7
      standard it is possible to model and map progress notes using SOAP headings and
      POMR methodology. We have developed a generic, flexible and applicable paradigm
      by using acts for each assessment that refer to a condition (1), by separating
      conditions from concerns (2), and by an extensive use of the working list act
      (3).

PMID- 23154580
TI  - The metabolic activity of gut microbiota in obese children is increased compared
      with normal-weight children and exhibits more exhaustive substrate utilization.
AB  - OBJECTIVE: The gut microbiota contribute otherwise impossible metabolic functions
      to the human host. Shifts in the relative proportions of gut microbial
      communities in adults have been correlated with intestinal disease and have been
      associated with obesity. The aim of this study was to elucidate differences in
      gut microbial compositions and metabolite concentrations of obese versus normal
      weight children. MATERIALS AND METHODS: Fecal samples were obtained from obese
      (n=15; mean body mass index (BMI) s.d. score=1.95) and normal-weight (n=15; BMI
      s.d. score=-0.14) Swiss children aged 8-14 years. Composition and diversity of
      gut microbiota were analyzed by qPCR and temperature gradient gel electrophoresis
      (TGGE). RESULTS: No significant quantitative differences in gut microbiota
      communities of obese and normal-weight children were identified. Microbial
      community profiling by TGGE revealed a high degree of both intra- and intergroup
      variation. Intergroup comparison of TGGE profiles failed to identify any distinct
      populations exclusive to either obese or normal-weight children. High-pressure
      liquid chromatography analysis identified significantly higher (P<0.05)
      concentrations of short-chain fatty acids (SCFA) butyrate and propionate in obese
      versus normal-weight children. Significantly lower concentrations of intermediate
      metabolites were detected in obese children, suggesting exhaustive substrate
      utilization by obese gut microbiota. CONCLUSIONS: Our results indicate that a
      dysbiosis may be involved in the etiology of childhood obesity. In turn, aberrant
      and overactive metabolic activity within the intestine could dictate survival or
      loss of individual microbial communities, leading to the altered population
      ratios previously identified in adult obesity.

PMID- 23154582
TI  - Applications of asymmetric organocatalysis in medicinal chemistry.
AB  - In the last decade, organocatalysis, the use of small chiral organic molecules as
      catalysts, has proven to be a valuable and attractive tool for the synthesis of
      enantiomerically enriched molecules. A number of organocatalysts and processes,
      such as one-pot, tandem, cascade or multicomponent reactions, have been reported
      to date. Furthermore, the many advantages of organocatalysis - robust, non-toxic,
      affordable, inert atmosphere, easy reaction manipulation, etc. - allow the
      preparation of bioactive compounds using simple and metal-free procedures, thus
      avoiding false positives in the biological evaluation. This mini-review focuses
      on medicinal chemistry programs that have synthesized biologically active
      compounds using one or more organocatalytic steps. In this respect, the potential
      of organocatalytic methods for enabling the chemical synthesis of important
      medicinal targets will be highlighted.

PMID- 23154583
TI  - A new approach to kinematic feature extraction from the human right ventricle for
      classification of hypertension: a feasibility study.
AB  - This work presents a novel approach to analyze the function of the human right
      ventricle (RV) by deriving kinematic features of the relative change in shape
      throughout the cardiac cycle. The approach is anatomically consistent, allows
      direct comparison across populations of individuals, and potentially provides new
      metrics to improve the diagnosis and understanding of cardiovascular diseases
      such as pulmonary hypertension (PH). The details of the approach are presented,
      which includes a variation of harmonic topological mapping and proper orthogonal
      decomposition techniques, with particular focus on their applicability with
      respect to untagged cardiac imaging data. Results are shown for the decomposition
      of a collection of clinically obtained human RV endocardial surfaces segmented
      from cardiac computed tomography imaging into the fundamental shape change
      features for individuals both with and without PH. The features are shown to be
      consistent and converging towards intrinsically physiological components for the
      heart, and may potentially represent a new set of features for classifying the
      progressive change in RV function caused by PH, particularly in comparison to
      traditional clinical metrics.

PMID- 23154584
TI  - Distinct transcriptional control in major immunogenetic subsets of chronic
      lymphocytic leukemia exhibiting subset-biased global DNA methylation profiles.
AB  - Chronic lymphocytic leukemia (CLL) can be divided into prognostic subgroups based
      on the IGHV gene mutational status, and is further characterized by multiple
      subsets of cases with quasi-identical or stereotyped B cell receptors that also
      share clinical and biological features. We recently reported differential DNA
      methylation profiles in IGHV-mutated and IGHV-unmutated CLL subgroups. For the
      first time, we here explore the global methylation profiles of stereotyped
      subsets with different prognosis, by applying high-resolution methylation arrays
      on CLL samples from three major stereotyped subsets: the poor-prognostic subsets
      #1 (n = 15) and #2 (n = 9) and the favorable-prognostic subset #4 (n = 15).
      Overall, the three subsets exhibited significantly different methylation
      profiles, which only partially overlapped with those observed in our previous
      study according to IGHV gene mutational status. Specifically, gene ontology
      analysis of the differentially methylated genes revealed a clear enrichment of
      genes involved in immune response, such as B cell activation (e.g., CD80, CD86
      and IL10), with higher methylation levels in subset #1 than subsets #2 and #4.
      Accordingly, higher expression of the co-stimulatory molecules CD80 and CD86 was
      demonstrated in subset #4 vs. subset #1, pointing to a key role for these
      molecules in the crosstalk of CLL subset #4 cells with the microenvironment. In
      summary, investigation of three prototypic, stereotyped CLL subsets revealed
      distinct DNA methylation profiles for each subset, which suggests subset-biased
      patterns of transcriptional control and highlights a key role for epigenetics
      during leukemogenesis.

PMID- 23154585
TI  - Hypertension and the J-curve phenomenon: implications for tight blood pressure
      control.

PMID- 23154586
TI  - Response to Rai.

PMID- 23154588
TI  - Increased blood viscosity is associated with reduced renal function and elevated
      urinary albumin excretion in essential hypertensives without chronic kidney
      disease.
AB  - Increased blood viscosity reduces blood flow and elevates vascular resistance in
      the cardiovascular system. The aim of this study was to elucidate how blood
      viscosity could affect renal function and eventually contribute to renal damage
      in essential hypertensives (EHT). In 164 untreated EHT without apparent renal
      damage (96 men, 56+/-12 years old, creatinine clearance 123+/-33 ml min(-1) per
      1.73 m(2) and urinary albumin excretion 19+/-19 mg per day), blood and plasma
      viscosity was determined using a falling ball microviscometer. Blood viscosity
      correlated negatively with creatinine clearance (r=-0.185, P=0.018) and
      positively with urinary albumin excretion (r=0.253, P=0.001). This indicated that
      increased blood viscosity is associated with reduced renal function and worsening
      of albuminuria in EHT. Stepwise multiple regression analysis identified blood
      viscosity as an independent determinant of creatinine clearance (R(2)=0.058) and
      urinary albumin excretion (R(2)=0.216). In conclusion, increased blood viscosity
      may be a risk for development of renal disease in EHT.

PMID- 23154587
TI  - The angiotensin II type 1 receptor blocker olmesartan preferentially improves
      nocturnal hypertension and proteinuria in chronic kidney disease.
AB  - Accumulated evidence suggests that an altered ambulatory blood pressure (BP)
      profile, particularly elevated nighttime BP, reflects target organ injury and is
      a better predictor of further cardiorenal risk than the clinic BP or daytime BP
      in hypertensive patients complicated by chronic kidney disease (CKD). In this
      study, we examined the beneficial effects of olmesartan, an angiotensin II type 1
      receptor blocker (ARB), on ambulatory BP profiles and renal function in
      hypertensive CKD patients. Forty-six patients were randomly assigned to the
      olmesartan add-on group (n=23) or the non-ARB group (n=23). At baseline and after
      the 16-week treatment period, ambulatory BP monitoring was performed and renal
      function parameter measurements were collected. Although the baseline clinic BP
      levels and the after-treatment/baseline (A/B) ratios of clinic BP levels were
      similar in the olmesartan add-on and non-ARB groups, the A/B ratios of ambulatory
      24-h and nighttime BP levels in the olmesartan add-on group were significantly
      lower. Furthermore, the A/B ratios of urinary protein, albumin and type IV
      collagen excretion in the olmesartan add-on group were significantly lower than
      those in the non-ARB group (urinary protein excretion, 0.72+/-0.41 vs. 1.45+/
      1.48, P=0.030; urinary albumin excretion, 0.73+/-0.37 vs. 1.50+/-1.37, P=0.005;
      urinary type IV collagen excretion, 0.87+/-0.42 vs. 1.48+/-0.87, P=0.014) despite
      comparable A/B ratios for the estimated glomerular filtration rate in the two
      groups. These results indicate that in hypertensive patients with CKD, olmesartan
      add-on therapy improves the ambulatory BP profile via a preferential reduction in
      nighttime BP with concomitant renal injury inhibition.

PMID- 23154589
TI  - Aliskiren vs. other antihypertensive drugs in the treatment of hypertension: a
      meta-analysis.
AB  - To investigate the antihypertensive effects and tolerability of aliskiren in
      comparison with other antihypertensive drugs and placebo in patients with
      hypertension, a meta-analysis was performed of studies published between 1950 and
      2012. A systematic literature search of MEDLINE and the Cochrane Library was
      conducted for randomized controlled trials. Weighted mean differences and
      relative risk with 95% confidence intervals were calculated for continuous and
      dichotomous data, respectively. In all, 14 studies with 6741 participants were
      included in the present meta-analysis. Nine studies included trial arms with
      placebo, four included angiotensin (Ang) AT1 receptor blockers (ARBs), three
      included Ang-converting enzyme inhibitors (ACEIs), two included calcium channel
      blockers (CCBs), one included a beta-blocker, and one included
      hydrochlorothiazide (HCTZ). We found that aliskiren, which lowered blood pressure
      (BP) effectively in patients with mild-to-moderate hypertension, was similar to
      HCTZ but inferior to CCBs in BP reduction, response rates and control rates.
      Furthermore, aliskiren was superior to ACEIs in lowering diastolic BP (DBP),
      while it had similar effects to ACEIs on systolic BP (SBP) reduction, response
      rates and control rates. Additionally, the present meta-analysis showed the
      superiority of atenolol over aliskiren in DBP reduction and BP response but
      showed that atenolol was inferior in SBP reduction and BP control. No difference
      was found in the rates of therapeutic response between aliskiren and ARBs, while
      more patients achieved BP control with aliskiren. Further studies will be needed
      to determine the antihypertensive effects and tolerability of aliskiren in
      comparison with other antihypertensive drugs.

PMID- 23154590
TI  - The effects of telmisartan alone or with hydrochlorothiazide on morning and 24-h
      ambulatory BP control: results from a practice-based study (SURGE 2).
AB  - Observational studies have shown that 24-h and morning ambulatory blood pressure
      (BP) control is low. This large-scale, practice-based study evaluated the effects
      of telmisartan 40 or 80 mg alone or in combination with hydrochlorothiazide
      (HCTZ) 12.5 mg on these BP parameters over 8 weeks; treatment was adjusted if
      clinic BP remained >=140/90 mm Hg. A total of 863 patients were evaluated
      (baseline mean clinic BP, morning and 24-h ambulatory BP: 155+/-15/93+/-10 mm Hg,
      137+/-15/83+/-11 mm Hg, 133+/-14/79+/-10 mm Hg, respectively; 68% were previously
      treated at baseline). Telmisartan with/without HCTZ significantly reduced the
      mean morning ambulatory BP (-8.2/-4.9 mm Hg), daytime ambulatory BP (-8.0/-4.7 mm
      Hg), 24-h ambulatory BP (-7.9/-4.7 mm Hg) and clinic BP (-22.3/-13.2 mm Hg) (all
      P<0.001) in previously untreated and in treated patients who switched to
      telmisartan and telmisartan/HCTZ. After treatment with telmisartan with/without
      HCTZ, the morning ambulatory BP control increased from 36.5 to 64.4%; daytime
      ambulatory BP control increased from 40.8 to 67.6%; 53.0% of patients achieved 24
      h ambulatory BP <125/80 mm Hg and 62% achieved <130/80 mm Hg targets. Only 0.8%
      (7/863) reported an adverse event. In summary, telmisartan and telmisartan/HCTZ
      increased smooth 24-h BP control in daily management of hypertension.

PMID- 23154592
TI  - Effects and cost-effectiveness of a guideline-oriented primary healthcare
      hypertension management program in Beijing, China: results from a 1-year
      controlled trial.
AB  - Hypertension control rates are unacceptably low in China. The present study
      demonstrates if a customized, guideline-oriented training program can cost
      effectively improve hypertension management in primary healthcare. Four typical
      community health centers in Beijing were selected and randomized to intervention
      or control (one urban and one rural each). A sample of 140 patients with
      hypertension and blood pressure uncontrolled was recruited from each center.
      Primary healthcare providers in intervention centers provided management to the
      recruited patients for 1 year after receiving training with customized
      hypertension management guidelines, and primary healthcare providers in control
      provided with usual care. Intention-to-treat analysis showed that hypertension
      control (systolic blood pressure (SBP) <140 mm Hg and diastolic blood pressure
      (DBP) <90 mm Hg)) rate was significantly higher in interventions than controls at
      month 3 (42.1% vs. 34.3% in urban and 30.7% vs. 10.0% in rural centers) and the
      trend increased to month 12 (70.7% vs. 40.0% in urban and 72.9% vs. 27.9% in
      rural); P-values by logistic mixed model were all <0.001 for both urban and rural
      after adjustment for baseline multiple variables including blood pressure. Mean
      reductions of SBP and DBP were significantly larger in interventions. The
      intervention was cost-saving, with an average incremental cost-saving of US$ 20.3
      per patient in urban sites and $ 7.0 per patient in rural sites. Corresponding
      results from per-protocol analysis were very similar. The customized, guideline
      oriented hypertension management program in primary healthcare in China
      effectively improved blood pressure control and was cost-saving.

PMID- 23154593
TI  - An update on the drug treatment of neuropathic pain. Part 2: antiepileptics and
      other drugs.
AB  - In An update on the drug treatment of neuropathic pain. Part 1: antidepressants,
      we highlighted the problems associated with the management of neuropathic pain
      and reviewed the use of antidepressants. This month we discuss the use of
      antiepileptic drugs and other analgesics.

PMID- 23154591
TI  - Effects of valsartan on progression of kidney disease in Japanese hypertensive
      patients with advanced, predialysis, chronic kidney disease: Kanagawa Valsartan
      Trial (KVT).
AB  - Suppression of the renin-angiotensin system is known to slow progression of
      chronic kidney disease (CKD). However, few trials have been performed with
      Japanese patients. This study investigated whether the angiotensin receptor
      blocker (ARB) valsartan would delay the progression of kidney disease more
      effectively than conventional treatment in Japanese hypertensive patients with
      advanced, predialysis CKD. In a multicenter, randomized, open-label trial, 303
      patients with hypertension and CKD with serum creatinine levels ?2.0 mg dl(-1)
      were assigned to receive either conventional therapy plus valsartan (valsartan
      add-on group) or conventional therapy without ARB (control group). The primary
      outcome was a change in serum creatinine levels. Changes in urinary protein
      levels and time to onset of renal events were analyzed as secondary end points.
      There were no between-group differences in blood pressure during the study.
      Changes in serum creatinine and urinary protein levels did not differ between the
      groups. However, the rate of renal events, including doubling of serum creatinine
      levels or end-stage renal disease, was significantly lower in the valsartan add
      on group than in the control group. The addition of valsartan decreased the risk
      by 42.6% after adjustment for baseline variables. The addition of valsartan to
      conventional therapy significantly slowed the rate of renal function decline and
      delayed the need for renal replacement therapy in Japanese hypertensive patients
      with advanced CKD.

PMID- 23154594
TI  - Fidaxomicin for the treatment of Clostridium difficile infections.
AB  - Clostridium difficile infection (CDI), also known as C. difficile-associated
      disease or diarrhoea (CDAD), is an important cause of hospital-acquired diarrhoea
      with disease severity ranging from mild diarrhoea to fulminant colitis. In
      addition, over 40% of new cases of CDI occur outside hospital. ? Fidaxomicin
      (Dificlir - Astellas), the first antibiotic in a new class called macrocyclics,
      has recently been licensed for the treatment of C. difficile infection in adults.
      Here we provide a brief overview of C. difficile infection and assess how
      fidaxomicin fits with current management strategies for treatment of such
      infections.

PMID- 23154596
TI  - Judging too quickly?

PMID- 23154598
TI  - Current world literature.

PMID- 23154597
TI  - What do you do? Perceptions of nurse manager responsibilities.

PMID- 23154600
TI  - Improvement in hematopoiesis after iron chelation therapy with deferasirox in
      patients with aplastic anemia.
AB  - Iron overload due to regular transfusions of packed red cells can cause multiple
      organ damage. Iron chelation therapy (ICT) is important in patients with aplastic
      anemia (AA) who require blood transfusions as supportive management. With the
      introduction of the oral iron chelator deferasirox, ICT has become more widely
      available and feasible. We studied 4 adult AA patients who had transfusion
      induced iron overload and showed hematological improvement after ICT with oral
      deferasirox. Following deferasirox treatment, hemoglobin increased and serum
      ferritin levels decreased, and the patients subsequently became transfusion
      independent. Our experience raises the possibility of the potential benefit of
      ICT on hematopoiesis. Further long-term studies in larger patient cohorts are
      needed to clarify the effect of the restoration of hematopoiesis after iron
      chelation therapy.

PMID- 23154601
TI  - Light-responsive polymer nanoreactors: a source of reactive oxygen species on
      demand.
AB  - Various domains present the challenges of responding to stimuli in a specific
      manner, with the desired sensitivity or functionality, and only when required.
      Stimuli-responsive systems that are appropriately designed can effectively meet
      these challenges. Here, we introduce nanoreactors that encapsulate
      photosensitizer-protein conjugates in polymer vesicles as a source of "on demand"
      reactive oxygen species. Vesicles made of poly(2-methyloxazoline)
      poly(dimethylsiloxane)-poly(2-methyloxazoline) successfully encapsulated the
      photosensitizer Rose Bengal-bovine serum albumin conjugate (RB-BSA) during a self
      assembly process, as demonstrated by UV-Vis spectroscopy. A combination of light
      scattering and transmission electron microscopy indicated that the nanoreactors
      are stable over time. They serve a dual role: protecting the photosensitizer in
      the inner cavity and producing in situ reactive oxygen species (ROS) upon
      irradiation with appropriate electromagnetic radiation. Illumination with
      appropriate wavelength light allows us to switch on/off and to control the
      production of ROS. Because of the oxygen-permeable nature of the polymer membrane
      of vesicles, ROS escape into the environment around vesicles, as established by
      electron paramagnetic resonance. The light-sensitive nanoreactor is taken up by
      HeLa cells in a Trojan horse fashion: it is nontoxic and, when irradiated with
      the appropriate laser light, produces ROS that induce cell death in a precise
      area corresponding to the irradiation zone. These nanoreactors can be used in
      theranostic approaches because they can be detected via the fluorescent
      photosensitizer signal and simultaneously produce ROS efficiently "on demand".

PMID- 23154603
TI  - Predictive tools for prostate cancer staging, treatment response and outcomes.
AB  - OBJECTIVES: Numerous predictive models relating to prostate cancer staging and
      outcomes have been described. We sought to review and categorize these predictive
      tools to  create a comprehensive reference for physicians who treat prostate
      cancer. METHODS: We performed a search of MEDLINE literature from January 1966 to
      April 2012 to identify predictive models relating to prostate cancer staging,
      treatment,  and outcomes in the pre-treated patient. For each model identified,
      we describe the outcome predicted, the variables comprising the model, the size
      of the cohort on which the tool was developed, predictive discrimination
      estimates, and whether internal and/or external validation has been performed.
      RESULTS: We identified 80 predictive tools applicable to pre-treated prostate
      cancer patients, 30 of which had been externally validated. Tools designed to
      predict  pathologic stage were the most common; several models focused on
      accurately predicting clinically insignificant prostate cancer while another
      large proportion focused  on the prediction of locally advanced disease (i.e.
      extracapsular extension, seminal vesicle involvement, lymph node invasion). Other
      models described  studied biochemical  outcomes following radical prostatectomy,
      external beam radiotherapy, or brachytherapy. Very few models addressed the
      prediction of metastasis and survival. Finally,  several tools incorporated novel
      pre-treatment serum biomarkers or magnetic resonance imaging findings into base
      models to enhance the accuracy of standard  clinicopathologic  variables.
      CONCLUSION: To deliver optimal, individualized prostate cancer care, treatment
      should be tailored to the specific characteristics of each patient and each
      tumor.  Predictive models may facilitate such an approach and are numerously
      described in the literature. While the performance of predictive models is
      encouraging, further  improvement through inclusion of biomarkers as well as
      evaluation of their clinical utility is imperative. Optimally, predictive models
      should be further studied in  the prospective setting.

PMID- 23154604
TI  - Quality perception in the outpatient area of an Urology department. Can we
      improve it?
AB  - OBJECTIVES: To test patient's satisfaction after consultation in the outpatient
      area of the Urology Department in a public hospital using a structured interview.
      METHODS: We used the Comunidad Autonoma de Madrid (CAM) standard interview form
      modified to include three questions related to the implementation of a 'one
      visit'policy and nurses' empowerment. Patients' opinions were gathered with
      respect to waiting times in the waiting room, facilities, and staff kindness and
      professionalism. Sample size was estimated in 386 patients. The effect of every
      predictive factor on the overall satisfaction was tested using the chi square
      test. To define the effect of every variable in presence of the rest of
      covariates a logistic regression model was used. RESULTS: Participation reached
      65.5%. Overall, 86.4% of the patients were satisfied. Irrespectively of the
      professional and personal style, the quality perception was homogeneous (p=ns).
      Multivariate analysis couldn't disclose any independent predictive variable. Only
      the perception in the item 'overall time available for the consultation'
      approached statistical significance (p=0.08), with patients scoring high in this
      variable getting the highest overall satisfaction scores. CONCLUSIONS: There was
      no personal or professional style particularly related with patient satisfaction.
      Nevertheless, there is a slight trend towards a higher satisfaction when patients
      feel enough time has been spent in their consultation. The new organizational
      resources (one-visit clinic and nurses' empowerment) are both welcome but are not
      clearly related to patient satisfaction.

PMID- 23154605
TI  - Higher second fourth digit ratio predicts higher incidence of prostate cancer in
      prostate biopsy.
AB  - OBJECTIVES: To analyze the validity of the ratio between the second and fourth
      finger (digit ratio; 2D/4D) of the left hand as a predictor for prostate cancer
      (PCa) in a group of men undergoing prostate biopsy. METHODS: We prospectively
      recruited 204 consecutive patients referred for transrectal prostate biopsy due
      to PSA elevation or abnormal digital rectal examination between January 2008 and
      June 2009. The same physician performed all clinical examinations, digit ratio
      measurements and transrectal biopsy in all cases. Digit ratio determination was
      done with a Vernier caliper in the left hand. Patients underwent determination of
      hormone profile (testosterone and sexual hormone binding globulin (SHBG)) between
      7:00AM and 11:00AM. Age, digital rectal examination, PSA, free PSA, PSA density,
      testosterone and SHBG, pathological report and D2 and D4 measurements were
      recorded prospectively. RESULTS: Variables age and SHBG were directly related to
      PCa. Prostate volume was inversely related to neoplasia. 2D/4D ratio >0,95 (OR
      (CI 95%) 4,4 (1,491-13,107) was related to neoplasia. No differences in PCa were
      seen regarding PSA, free PSA, PSA density, digital rectal examination and
      testosterone. CONCLUSION: High digit ratio predicts PCa in men undergoing
      prostate biopsy. Digit ratio >0,95 has 4-fold risk of PCa compared to men with
      digit ratio <=0.95.

PMID- 23154606
TI  - Clinical profile and epidemiological changes of clear cell renal carcinoma during
      12 years in our health area.
AB  - OBJECTIVES: To investigate changes in the epidemiology and clinical profile of
      patients diagnosed with renal clear cell carcinoma in a community health area
      over 12 years. METHODS: Retrospective analysis of epidemiological characteristics
      and clinical profile of patients diagnosed with renal clear cell carcinoma in a
      health area composed of a population of 353.619 inhabitants from January 1999 to
      December 2010. Descriptive statistical and multivariate analysis, Fisher exact
      test and Chi-Square were utilized. p<0.05 was accepted as significant. RESULTS:
      349 diagnoses of renal mass were reported; 165 of them were clear renal cell
      carcinoma. Median age was 70.41 years, and the Female/Male rate was 28% and 72%,
      respectively. 4% women and 30% men smoked >=20 cigarettes/day, more frequently
      during the period 1999-2001. 52% women and 30% men had hypertension. Hematuria
      was the most frequent symptom (23%), more frequent in the period 2007-2010,
      followed by abdominal pain (16%) and renal colic(13%). Weight loss (12%) was more
      frequent between 1999-2000. Asthenia appeared as the first symptom in 8% of
      cases. The tumor was incidentally diagnosed in 20% of cases, more frequently in
      the period between 2007-2010. Diagnosis was established in the Urology Department
      in 36% of the cases. Stages T1-2 N0 were more frequent between 2007-2010, and M1
      between 1999-2000. G3 was more frequent in the entire series. The relative cancer
      specific mortality of patients who were surgically treated was less in the last 2
      years of the period. CONCLUSIONS: Clear renal cell carcinoma is the most frequent
      renal cancer and its incidence is increasing in our environment. It affects more
      frequently males than females, and at an earlier age. The last few years are
      showing a decrease in the habitual smoker males and an increase in HTN in
      females. A tendency has been detected to the early stage clinical diagnosis but
      with a higher histopathological grade. It is most frequent diagnosed by a non
      Urology speciality.

PMID- 23154607
TI  - Robot assisted partial nephrectomy (Da Vinci) in an angiomyolipoma associated to
      Wunderlich Syndrome.
AB  - OBJECTIVE: To describe a case of renal angiomyolipoma treated by robotic assisted
      surgery. METHOD AND RESULTS: We report the case of a 26 year old females patient,
      in the context of third month pregnancy, who was diagnosed of spontaneous self
      limited retroperitoneal hemorrhage due to renal angiomyolipoma. The patient was
      treated conservatively until normal delivery. At the 3rd month postpartum a robot
      assisted (Da Vinci S) nephron sparing surgery (partial nephrectomy) was
      performed. CONCLUSION: Despite being a benign tumor, there are cases in which the
      renal angiomyolipoma requires surgical treatment. To our knowledge, after a
      thorough review of the literature, this would be the first reported case of
      angiomyolipoma treated with conservative surgery with robotic assistance (Da
      Vinci S-HD).

PMID- 23154608
TI  - Bladder injury during trans-obturator tape surgery in a patient with previous
      colposuspension: is there a connection?
AB  - OBJECTIVE: Bladder injuries are quite rare and complex complications of
      transobturator tapes in the treatment of female  stress urinary incontinence,
      with very few published cases. The authors present a case report and discuss
      possible injury  mechanisms and the role of cystoscopy in this setting. METHODS:
      A 51 year-old female with past surgical history of Burch colposuspension
      underwent an uneventful transobturator  tape surgery. After 15 days, she
      complained of dysuria and frequency. Cystoscopy revealed the tape protruding
      within the  bladder. RESULTS: Reoperation was performed with the sub-urethral
      segment of the tape removed by vaginal approach and the vesical  one excised
      endoscopically. Presently, the patient is asymptomatic. CONCLUSIONS: In patients
      with previous incontinence surgical treatments, cystoscopy at the time of surgery
      should be  considered to exclude and treat eventual injuries, in order to avoid
      future complications.

PMID- 23154609
TI  - Percutaneous endopyelotomy with electrocautery: modified techniques in the
      treatment of ureteropelvic junction obstruction in a child under 2 years.
AB  - OBJECTIVE: In recent years new techniques in minimally invasive treatment of
      congenital stenosis of ureteropelvic junction have been developed.  We report the
      treatment of pyeloureteral stenosis in children by percutaneous endopyelotomy.
      METHODS: In the work up study of a child (18 months) with abdominal palpable
      mass, a severe left hydronephrosis  with a renal pelvis diameter of 65 mm and
      severely thinned renal parenchyma was found. The diuretic renogram showed an
      obstructive pattern  with impaired renal function. Initially, a retrograde
      dilatation balloon was placed in the ureteropelvic junction under cistoscopic
      control.  With the patient in modified Valdivia position, percutaneous access to
      the renal pelvis was performed. By Seldinger technique and under fluoroscopy
      guide, a 5 mm laparoscopic trocar was placed in the renal pelvis. We performed a
      percutaneous electrical endopyelotomy of the pyeloureteral junction over the 6 mm
      retrograde balloon dilator passed through.  We placed an antegrade double J stent
      that was removed at 4 weeks uneventfully. RESULT: Good results were assessed
      without perioperative or postoperative complications with great improvement in
      renal dilatation two years  after the intervention. The renogram showed
      improvement in the pattern of the curve with a slight increase in differential
      renal function. CONCLUSIONS: Percutaneous endopyelotomy in children has important
      issues due to the lack of appropriate material. However it is possible to  get
      good results as a minimally invasive technique. In fact, it could be the ideal
      technique in severe hydronephrosis with large renal  pelvis that prevents the
      surgical or endourological approach.

PMID- 23154610
TI  - Tubulocystic renal carcinoma (low grade collecting duct carcinoma).
AB  - OBJECTIVE: To report a case of tubulocystic renal carcinoma diagnosed in an
      adult, after a work up study for hematuria. METHODS/RESULTS: 59-year-old male, CT
      scan was performed during a study for self-limited hematuria showing a 4.2 cm
      solid mass with areas suspicious of pseudocystic malignancy. Due to its debut
      with hematuria and renal sinus involvement laparoscopic radical nephrectomy was
      performed, establishing the diagnosis of tubulocystic carcinoma (low grade
      collecting duct carcinoma). CONCLUSION: Tubulocystic carcinoma presents
      histological characteristics and a natural history that makes it different from
      the classic type of Bellini duct carcinoma, the latter being a rapidly growing
      tumor with poor prognosis which is usually diagnosed in advanced stages.

PMID- 23154611
TI  - Vesicoureteral refulx in overactive bladder: medical resolution through botulin
      toxin injection.
AB  - OBJECTIVE: Overactive bladder may have a neurogenic or non neurogenic origin.
      Sometimes, as a result of detrusor overactivity, disorders of the  upper urinary
      tract function may appear. One of these alterations may be the appearance of
      associated vesicoureteral reflux. The treatment  of overactive bladder may be
      done with anticholinergic drugs and if there is not response the use of botulin
      toxin type A is approved. The aim of this case report is to demonstrate the
      effect of botulin toxin type A in the treatment of overactive bladder and
      vesicoureteral  reflux secondary to the overactive bladder. METHOD: We present
      the case of a 10-year-old patient without significant past medical history. When
      he was one year old he had a urinary  infection and voiding cystourethrogram
      showed grade 1 right vesicoureteral reflux. When he was 4 year old he presented
      several episodes  of pyelonephritis and then he was diagnosed of severe bilateral
      vesicoureteral reflux, which did not respond to treatment with Macroplastic (r) 
      or Deflux (r). Urodynamic study was performed showing overactive bladder with
      decreased bladder compliance. RESULTS: We performed intravesical injection of 200
      U of botulin toxin type A and vesicoureteral reflux disappeared and urodynamic
      study  improved. One year later we re-injected botulin toxin type A (300 U) and
      we repeated the injection after one year (300 U). The patient is  currently well,
      without changes in the urodynamic study and without vesicoureteral reflux.
      CONCLUSION: Repeated injections of botulin toxin type A has shown great efficacy
      in the treatment of overactive bladder in children with  vesicoureteral reflux
      improved secondary.

PMID- 23154612
TI  - Complete bilateral pelvicalyceal system duplication.

PMID- 23154613
TI  - Renal pelvis tumour.

PMID- 23154614
TI  - Using alkaline-earth metal ions to tune structural variations of 1,3,5
      benzenetricarboxylate coordination polymers.
AB  - Alkaline-earth metal ions were used to tune four new heterometallic frameworks,
      {[Cd(2.07)Mg(0.93)(BTC)(2)(H(2)O)(4)].2H(2)O}(n) (1),
      {[Cd(2)Ca(BTC)(2)(H(2)O)(4)].2H(2)O}(n) (2),
      {[Cd(2)Sr(BTC)(2)(H(2)O)(5)].H(2)O}(n) (3) and [Cd(6)Ba(3)(BTC)(3)(H(2)O)(10)](n)
      (4) (H(3)BTC = 1,3,5-benzenetricarboxylic acid), synthesized from H(3)BTC and the
      corresponding metal salts. Single-crystal X-ray analysis shows that compound 1 is
      a three-dimensional (3D) framework based on heterometallic Cd-O-Cd-O-Mg inorganic
      chain subunits, compounds 2 and 3 are basically isostructural and feature a 3D
      framework based on Ca(II) or Sr(II) polyhedrons decorated with Cd-O-Cd inorganic
      chains. Compound 4 is a 3D framework templated by disordered inorganic hydrate
      Ba(II) ions, and also features inorganic Cd-O-Cd chains, which are connected
      together through corner sharing with the {Cd(1)O(6)} polyhedrons by {Ba(1)O(6)}
      polyhedrons, giving rise to a rare heterometallic 3D inorganic skeleton.
      Moreover, the solid-state fluorescence of compounds 1-4 and NLO properties of
      compounds 2-4 have also been investigated at room temperature.

PMID- 23154615
TI  - Advances in growth factor delivery for therapeutic angiogenesis.
AB  - Therapeutic angiogenesis is a new revascularization strategy involving the
      administration of growth factors to induce new vessel formation. The biology and
      delivery of angiogenic growth factors involved in vessel formation have been
      extensively studied but success in translating the angiogenic capacity of growth
      factors into benefits for vascular disease patients is still limited. This could
      be attributed to issues related to patient selection, growth factor delivery
      methods or lack of vessel maturation. Comprehensive understanding of the cellular
      and molecular cross-talk during the different stages of vascular development is
      needed for the design of efficient therapeutic strategies. The presentation of
      angiogenic factors either in series or in parallel using a strategy that mimics
      physiological events, such as concentration and spatio-temporal profiles, is an
      immediate requirement for functional blood vessel formation. This review provides
      an overview of the recent delivery strategies of angiogenic factors and discusses
      targeting neovascular maturation as a promising approach to induce stable and
      functional vessels for therapeutic angiogenesis.

PMID- 23154616
TI  - Maternal serum soluble endoglin at 30-33 weeks in the prediction of preeclampsia.
AB  - OBJECTIVE: To investigate the potential value of maternal serum concentration of
      soluble endoglin (sEng) at 30-33 weeks' gestation in the prediction of
      preeclampsia (PE) developing at or after 34 weeks. METHODS: Serum sEng was
      measured at 11-13 and at 30-33 weeks' gestation in a case-control study of 50
      cases that developed PE at or after 34 weeks and 250 unaffected controls.
      Regression analysis was used to determine which of the factors amongst the
      maternal characteristics were significant predictors of first- and third
      trimester log10 sEng in the control group. The measured values of sEng were
      converted into multiples of the unaffected median (MoM) and the MoM values in the
      PE and controls were compared. RESULTS: The median sEng MoM at 30-33 weeks was
      significantly higher in the PE group (1.39, IQR 0.94-2.18) than in the controls
      (0.95, IQR 0.77-1.19), but at 11-13 weeks there was no significant difference
      between the groups. In screening by a combination of maternal characteristics and
      third-trimester sEng, the detection rates of intermediate- and late-PE, at a
      false-positive rate of 10%, were 64.3 and 50.0%, respectively. CONCLUSION:
      Screening by maternal characteristics and sEng at 30-33 weeks could identify most
      pregnancies that will subsequently develop PE.

PMID- 23154617
TI  - Bee venom at different concentrations modulates the aeroallergen-induced
      activation of nasal polyp epithelial cells.
AB  - Bee venom (BV) has long been used as an oriental traditional medicine for the
      control of pain and inflammation. However, BV's anti-inflammatory mechanisms
      remain unclear. This study aimed to clarify the potential clinical efficacy of BV
      concerning the anti-inflammatory effect on nasal epithelial cell inflammation.
      Nasal polyp epithelial cells were obtained from patients. Cells were exposed to
      Alternaria alternata, Aspergillus nigra, Dermatophagoides pteronyssinus,
      Dermatophagoides farina and lipopolysaccharide with or without various
      concentrations of BV. Interleukin (IL)-6, IL-8, and granulocyte macrophage colony
      stimulating factor were measured to determine the activation of epithelial cells.
      Nuclear factor-KB (NF-KB) and activator protein 1 expression and activity were
      determined with Western blot analysis and ELISA. Cytotoxicity of BV was measured
      using a CellTiter-96(r) aqueous cell proliferation assay kit. Cell survival was
      significantly decreased at BV concentrations exceeding 5 ug/ml. Fungi-induced
      cytokine production was more effectively inhibited by BV than house dust mite.
      Alternaria enhanced NF-KB expression, which was strongly inhibited by BV. BV
      appears to be relatively safe, and is of potential value for the treatment of
      airway inflammation and/or immunologic diseases.

PMID- 23154618
TI  - Semantic localization-driven partial image retrieval in CT series.
AB  - BACKGROUND: Picture archiving and communication systems (PACS) contain very large
      amounts of computed tomography (CT) data. When querying a PACS for a particular
      series, the user is often not interested in the complete series but in a certain
      region of interest (ROI), described e.g. by an example view in another series or
      an anatomical concept. OBJECTIVES: Restricting a retrieval query to such an ROI
      saves both loading time and navigational effort. In this paper, we propose an
      efficient method for defining and retrieving ROIs. METHODS: We employ
      interpolation and regression techniques for mapping the slices of a series to a
      newly generated standardized height atlas of the human body. RESULTS:
      Examinations of the accuracy and the saved input/output (I/O) costs of our new
      method on a repository of 1,360 CT series demonstrate the advantages of our
      system. Depending on the scope of the retrieval query, we can economize up to 99%
      of the total loading time. CONCLUSION: Our proposed method for flexible, context
      based, partial image retrieval enables the user to directly focus on the relevant
      portion of the image material and it targets the high potential of I/O cost
      reduction of a common PACS.

PMID- 23154620
TI  - Microfibrillar-associated protein 5 is linked with markers of obesity-related
      extracellular matrix remodeling and inflammation.
AB  - OBJECTIVE: Microfibrillar-associated protein 5 (MFAP5) is an extracellular matrix
      (ECM) glycoprotein, which is colocalized with microfibrils in elastin networks.
      Its function in adipose tissue (AT) is not known. We have recently shown that the
      expression of MFAP5 is downregulated in AT along with weight reduction (WR) in
      persons with metabolic syndrome (MetS). The aim of this work was to study whether
      the change of MFAP5 mRNA expression in response to WR is associated with markers
      of adiposity, glucose metabolism and insulin resistance in human AT. DESIGN:
      Weight reduction intervention study in parallel study design (The Genobin study).
      Altogether 46 obese subjects with impaired glucose tolerance and features of MetS
      were randomized to a WR (n=28) or a control group (n=18) lasting for 33 weeks.
      MEASUREMENTS: Circulating glucose and insulin concentrations were measured and
      subcutaneous AT biopsies were performed before and after the intervention. The
      mRNA expression was studied by quantitative real-time PCR (QPCR). RESULTS: QPCR
      of human AT biopsy samples confirmed that MFAP5 is highly expressed in AT and its
      expression is decreased during WR. The mRNA expression of MFAP5 correlated
      positively with body mass index, and the change in MFAP5 mRNA expression during
      WR correlated positively with the change of body fat mass. Furthermore, the MFAP5
      mRNA expression correlated negatively with circulating fasting concentrations of
      adiponectin and interleukin (IL)-1beta and positively with leptin, insulin and IL
      1Ra levels. In addition, the MFAP5 mRNA expression correlated positively with the
      mRNA expressions of peroxisome proliferator-activated receptor gamma, cyclin D2
      and A disintegrin and metalloproteinase domain 12, genes involved in AT
      remodeling. CONCLUSION: This study demonstrates that MFAP5 is highly expressed in
      human AT and is correlated with markers of insulin resistance. Furthermore, it is
      possible that MFAP5 is related to ECM remodeling during development of obesity.

PMID- 23154619
TI  - Current and emerging quantitative magnetic resonance imaging methods for
      assessing and predicting the response of breast cancer to neoadjuvant therapy.
AB  - Reliable early assessment of breast cancer response to neoadjuvant therapy (NAT)
      would provide considerable benefit to patient care and ongoing research efforts,
      and demand for accurate and noninvasive early-response biomarkers is likely to
      increase. Response assessment techniques derived from quantitative magnetic
      resonance imaging (MRI) hold great potential for integration into treatment
      algorithms and clinical trials. Quantitative MRI techniques already available for
      assessing breast cancer response to neoadjuvant therapy include lesion size
      measurement, dynamic contrast-enhanced MRI, diffusion-weighted MRI, and proton
      magnetic resonance spectroscopy. Emerging yet promising techniques include
      magnetization transfer MRI, chemical exchange saturation transfer MRI, magnetic
      resonance elastography, and hyperpolarized MR. Translating and incorporating
      these techniques into the clinical setting will require close attention to
      statistical validation methods, standardization and reproducibility of technique,
      and scanning protocol design.

PMID- 23154621
TI  - Adaptive-weighted total variation minimization for sparse data toward low-dose x
      ray computed tomography image reconstruction.
AB  - Previous studies have shown that by minimizing the total variation (TV) of the to
      be-estimated image with some data and other constraints, piecewise-smooth x-ray
      computed tomography (CT) can be reconstructed from sparse-view projection data
      without introducing notable artifacts. However, due to the piecewise constant
      assumption for the image, a conventional TV minimization algorithm often suffers
      from over-smoothness on the edges of the resulting image. To mitigate this
      drawback, we present an adaptive-weighted TV (AwTV) minimization algorithm in
      this paper. The presented AwTV model is derived by considering the anisotropic
      edge property among neighboring image voxels, where the associated weights are
      expressed as an exponential function and can be adaptively adjusted by the local
      image-intensity gradient for the purpose of preserving the edge details. Inspired
      by the previously reported TV-POCS (projection onto convex sets) implementation,
      a similar AwTV-POCS implementation was developed to minimize the AwTV subject to
      data and other constraints for the purpose of sparse-view low-dose CT image
      reconstruction. To evaluate the presented AwTV-POCS algorithm, both qualitative
      and quantitative studies were performed by computer simulations and phantom
      experiments. The results show that the presented AwTV-POCS algorithm can yield
      images with several notable gains, in terms of noise-resolution tradeoff plots
      and full-width at half-maximum values, as compared to the corresponding
      conventional TV-POCS algorithm.

PMID- 23154622
TI  - Effects of a fixed combination of losartan with hydrochlorothiazide on glucose
      tolerance in hypertensive patients uncontrolled with angiotensin ii receptor
      blockers alone.
AB  - AIM: The concomitant use of angiotensin II receptor blocker (ARB) with low doses
      of hydrochlorothiazide (HCTZ) may provide additional antihypertensive activity.
      HCTZ induces hypokalemia and hyperglycemia, while ARB slightly induces
      hyperkalemia. Recently, it has been reported that ARB/ HCTZ did not worsen
      fasting blood sugar levels; however, the detailed glucose tolerance change effect
      with combination therapy of ARB/HCTZ compared to ARB alone therapy remains to be
      investigated. METHODS: Treated non-diabetes mellitus (DM) hypertensive patients
      taking a common dose of ARB regimens, not achieving blood pressure (BP) goals,
      were switched to 50 mg Losartan/12.5 mg HCTZ combinations, and the 75 g oral
      glucose tolerance test (75 g OGTT) was performed before switching and after
      switching at 3 months. RESULTS: This study included 30 patients aged 66.5+/-8.7
      years, 67% women. Pre-switching BP 146.6+/-17.0/ 88.4+/-10.4 mmHg decreased and
      was maintained at a steady state, reaching 131.4+/-1.0/73.8+/-8.8 mmHg (p<0.001)
      3 months later. After switching, blood glucose levels on the 75 g OGTT at
      fasting, 30, 60 and 120 minutes were significantly decreased. Homeostasis model
      assessment as an index of insulin resistance and the whole body insulin
      sensitivity index were significantly ameliorated. CONCLUSIONS: On the 75 g OGTT,
      50 mg Losartan with 12.5 mg HCTZ combinations did not worsen glucose tolerance;
      moreover, they improved BP, insulin resistance and sensitivity in non-DM Japanese
      patients with essential hypertension uncontrolled with ARBs alone.

PMID- 23154623
TI  - Milestones in genetics of structural skin disorders.

PMID- 23154624
TI  - The complexity of elastic fiber biogenesis: the paradigm of cutis laxa.

PMID- 23154625
TI  - Heritable ectopic mineralization disorders: the paradigm of pseudoxanthoma
      elasticum.

PMID- 23154626
TI  - Molecular heterogeneity of blistering disorders: the paradigm of epidermolysis
      bullosa.

PMID- 23154627
TI  - Heritable filaggrin disorders: the paradigm of atopic dermatitis.

PMID- 23154629
TI  - Next-generation diagnostics for genodermatoses.

PMID- 23154628
TI  - Genetics of structural hair disorders.
AB  - The identification of causative genes carries the promise of new and innovative
      therapeutic strategies for both inherited and acquired hair disorders. Moreover,
      the delineation of the relationships between similar phenotypes, resulting from
      mutations affecting seemingly distinct regulatory pathways, paves the way to
      improved diagnosis and treatment. Finally, understanding the biological processes
      governing HF development and maintenance may have implications for more general
      disease processes in the skin, such as inflammation and cancer.

PMID- 23154630
TI  - Molecular therapeutics for heritable skin diseases.

PMID- 23154631
TI  - Heritable collagen disorders: the paradigm of the Ehlers-Danlos syndrome.

PMID- 23154632
TI  - The prion protein family: looking outside the central nervous system.
AB  - Although the pivotal implication of the host-encoded Prion protein, PrP, in the
      neuropathology of transmissible spongiform encephalopathy is known for decades,
      its biological role remains mostly elusive. Genetic inactivation is one way to
      assess such issue but, so far, PrP-knockout mice did not help much. However,
      recent reports involving (1) further studies of these mice during embryogenesis,
      (2) knockdown experiments in Zebrafish and (3) knockdown of Shadoo, a protein
      with PrP-like functional domains, in PrP-knockout mice, all suggested a role of
      the Prion protein family in early embryogenesis. This view is challenged by the
      recent report that PrP/Shadoo knockout mice are healthy and fertile. Although
      puzzling, these apparently contradictory data may on the contrary help at
      deciphering the Prion protein family role through focusing scientific attention
      outside the central nervous system and by helping the identification of other
      loci involved in the genetic robustness associated with PrP.

PMID- 23154633
TI  - Proteolytic clearance of extracellular alpha-synuclein as a new therapeutic
      approach against Parkinson disease.
AB  - Many neurodegenerative diseases such as Alzheimer disease and Parkinson disease
      show similar characteristics. They typically show deposits of protein aggregates,
      the formation of which is considered important in their pathogenesis. Recently,
      aggregation-prone proteins have been shown to spread between cells and so may
      contribute to the pathogenesis of diseases like prion disease. Such a
      pathogenesis pathway is possibly common to many neurodegenerative diseases. If
      confirmed, it could allow the development of therapeutic interventions against
      many such diseases. In Parkinson disease, alpha-synuclein, a major component of
      cytosolic protein inclusions named Lewy body, has been shown to be released and
      taken up by cells, which may facilitate its progressive pathological spreading
      between cells. Accordingly, inhibition of spreading by targeting extracellular
      alpha-synuclein may represent a new therapy against Parkinson disease. Research
      into the intercellular spreading of extracellular protein aggregations of alpha
      synuclein and its clearance pathway are reviewed here with a focus on the
      proteolytic clearance pathway as a therapeutic target for the treatment of
      Parkinson disease. Considering the similar characteristics of aggregation-prone
      proteins, these clearance systems might allow treatment of other
      neurodegenerative diseases beyond Parkinson disease.

PMID- 23154634
TI  - Cis phosphorylated tau as the earliest detectable pathogenic conformation in
      Alzheimer disease, offering novel diagnostic and therapeutic strategies.
AB  - After protein phosphorylation on certain serine or threonine residues preceding a
      proline (pSer/Thr-Pro), the function of certain phosphorylated protein is further
      regulated by cis-trans conformational change. Due to the lack of any tool to
      detect such two conformations in cells, however, it is not even known whether any
      cis or trans conformation exists in vivo, not to mention their conformation
      specific functions or regulation. We developed a novel peptide chemistry
      technology to generate the first pair of antibodies that can distinguish cis from
      trans pThr231-Pro tau. Cis, but not trans, pThr231-tau appears early in mild
      cognitive impairment (MCI) neurons and further accumulates in only degenerating
      neurons as Alzheimer disease (AD) progresses, localizing to dystrophic neurites,
      which are known to correlate well with memory loss. Unlike trans p-tau, the cis
      cannot promote microtubule assembly, and is more resistant to dephosphorylation
      and degradation and more prone to aggregation. Pin1 accelerates cis to trans
      isomerization to prevent tau pathology in AD. Thus, during MCI and AD
      development, cis pThr231-Pro tau is the earliest detectable pathogenic tau
      conformation and antibodies and vaccines against the pathogenic cis p-tau may be
      used for the early diagnosis and treatment of AD. These findings offer in vivo
      approach to study conformational regulation of Pro-directed phosphorylation
      signaling.

PMID- 23154636
TI  - The Mozart effect on task performance in a laparoscopic surgical simulator.
AB  - The Mozart Effect is a phenomenon whereby certain pieces of music induce
      temporary enhancement in "spatial temporal reasoning." To determine whether the
      Mozart Effect can improve surgical performance, 55 male volunteers (mean age =
      20.6 years, range = 16-27), novice to surgery, were timed as they completed an
      activity course on a laparoscopic simulator. Subjects were then randomized for
      exposure to 1 of 2 musical pieces by Mozart (n = 21) and Dream Theater (n = 19),
      after which they repeated the course. Following a 15-minute exposure to a
      nonmusical piece, subjects were exposed to one of the pieces and performed the
      activity course a third time. An additional group (n = 15) that was not
      corandomized performed the tasks without any exposure to music. The percent
      improvements in completion time between 3 successive trials were calculated for
      each subject and group means compared. In 2 of the tasks, subjects exposed to the
      Dream Theater piece achieved approximately 30% more improvement (26.7 +/- 8.3%)
      than those exposed to the Mozart piece (20.2 +/- 7.8%, P = .021) or to no music
      (20.4 +/- 9.1%, P = .049). Distinct patterns of covariance between baseline
      performance and subsequent improvement were observed for the different musical
      conditions and tasks. The data confirm the existence of a Mozart Effect and
      demonstrate for the first time its practical applicability. Prior exposure to
      certain pieces may enhance performance in practical skills requiring spatial
      temporal reasoning. 

PMID- 23154635
TI  - Cellular prion protein and Alzheimer disease: link to oligomeric amyloid-beta and
      neuronal cell death.
AB  - Soluble oligomeric amyloid-beta (Abeta) has been suggested to impair synaptic and
      neuronal function, leading to neurodegeneration that is clinically observed as
      the memory and cognitive dysfunction characteristic of Alzheimer disease, while
      the precise mechanism(s) whereby oligomeric Abeta causes neurotoxicity remains
      unknown. Recently, the cellular prion protein (PrP (C) ) was reported to be an
      essential co-factor in mediating the neurotoxic effect of oligomeric Abeta. Our
      recent study showed that Prnp (-/-) mice are resistant to the neurotoxic effect
      of oligomeric Abeta in vivo and in vitro. Furthermore, application of an anti-PrP
      (C) antibody or PrP (C) peptide was able to block oligomeric Abeta-induced
      neurotoxicity. These findings demonstrate that PrP (C) may be involved in
      neuropathologic conditions other than conventional prion diseases, i.e.,
      Creutzfeldt-Jakob disease.

PMID- 23154637
TI  - miR-133a regulates vitamin K 2,3-epoxide reductase complex subunit 1 (VKORC1), a
      key protein in the vitamin K cycle.
AB  - Regulation of key proteins by microRNAs (miRNAs) is an emergent field in
      biomedicine. Vitamin K 2,3-epoxide reductase complex subunit 1 (VKORC1) is a
      relevant molecule for cardiovascular diseases, since it is the target of oral
      anticoagulant drugs and plays a role in soft tissue calcification. The objective
      of this study was to determine the influence of miRNAs on the expression of
      VKORC1. Potential miRNAs targeting VKORC1 mRNA were searched by using online
      algorithms. Validation studies were carried out in HepG2 cells by using miRNA
      precursors; direct miRNA interaction was investigated with reporter assays. In
      silico studies identified two putative conserved binding sites for miR-133a and
      miR-137 on VKORC1 mRNA. Ex vivo studies showed that only miR-133a was expressed
      in liver; transfection of miRNA precursors of miR-133a in HepG2 cells reduced
      VKORC1 mRNA expression in a dose-dependent manner, as assessed by quantitative
      reverse transcriptase-polymerase chain reaction (qRT-PCR) as well as protein
      expression. Reporter assays in HEK293T cells showed that miR-133a interacts with
      the 3'UTR of VKORC1. Additionally, miR-133a levels correlated inversely with
      VKORC1 mRNA levels in 23 liver samples from healthy subjects. In conclusion, miR
      133a appears to have a direct regulatory effect on expression of VKORC1 in
      humans; this regulation may have potential importance for anticoagulant therapy
      or aortic calcification.

PMID- 23154638
TI  - Adeno-associated virus serotype 8 (AAV8) delivery of recombinant A20 to skeletal
      muscle reduces pathological activation of nuclear factor (NF)-kappaB in muscle of
      mdx mice.
AB  - Duchenne muscular dystrophy (DMD) is a genetic muscle disease caused by the
      absence of a functional dystrophin protein. Lack of dystrophin protein disrupts
      the dystrophin-glycoprotein complex causing muscle membrane instability and
      degeneration. One of the secondary manifestations resulting from lack of
      functional dystrophin in muscle tissue is an increased level of cytokines that
      recruit inflammatory cells, leading to chronic upregulation of the nuclear factor
      (NF)-kappaB. Negative regulators of the classical NF-kappaB pathway improve
      muscle health in the mdx mouse model for DMD. We have previously shown in vitro
      that a negative regulator of the NF-kappaB pathway, A20, plays a role in muscle
      regeneration. Here, we show that overexpression of A20 by using a muscle-specific
      promoter delivered with an adeno-associated virus serotype 8 (AAV8) vector to the
      mdx mouse decreases activation of the NF-kappaB pathway in skeletal muscle.
      Recombinant A20 expression resulted in a reduction in number of fibers with
      centrally placed nuclei and a reduction in the number of T cells infiltrating
      muscle transduced with the AAV8-A20 vector. Taken together, we conclude that
      overexpression of A20 in mdx skeletal muscle provides improved muscle health by
      reduction of chronic inflammation and muscle degeneration. These results suggest
      A20 is a potential therapeutic target to ameliorate symptoms of DMD.

PMID- 23154640
TI  - The use of 18F-fluoromethylcholine PET/CT in differentiating focal nodular
      hyperplasia from hepatocellular adenoma:  a prospective study of diagnostic
      accuracy.
AB  - INTRODUCTION: Diagnosis of focal nodular hyperplasia (FNH) and hepatocellular
      adenoma (HCA) using conventional imaging techniques can be difficult; however, it
      is important to differentiate between them as these benign liver tumors require
      different therapeutic strategies. The aim of our study was to prospectively
      evaluate the use of PET/computed tomography (CT) with F-fluoromethylcholine (F
      FCH) as a novel diagnostic approach in the differentiation between HCA and FNH.
      MATERIALS AND METHODS: Fifty-six consecutive patients with a suspicion of one or
      multiple HCAs or FNHs larger than 2 cm were prospectively included after written
      informed consent was obtained from them. All the patients underwent a PET/CT with
      F-FCH. Histopathology of the lesions was the standard of reference. The ratio of
      the standardized uptake value (SUV) of the lesions compared with normal liver
      uptake within the same patient was calculated. Statistical tests were evaluated
      at the 95% confidence interval. RESULTS: Forty-nine patients with 60 lesions and
      histopathological diagnosis of FNH or HCA completed the study and were analyzed.
      The mean SUV ratio for FNH was 1.67+/-0.31 (mean+/-SD, n=28), resulting in a
      positive likelihood ratio of 32.3 for PET-positive FNH. The mean SUV ratio for
      HCA was 0.82+/-0.17 (n=32), with a likelihood ratio of ~100 for PET-negative HCA.
      Receiver operating characteristic curve analysis revealed an optimal SUV ratio
      cutoff value of 1.13, which reached 100% sensitivity and 97% specificity in
      differentiating FNH from HCA. CONCLUSION: This prospective study shows that
      PET/CT with F-FCH can accurately differentiate FNH from HCA and may become a
      valuable diagnostic tool when conventional imaging techniques fail to do so.

PMID- 23154639
TI  - STAT1, STAT6 and adenosine 3',5'-cyclic monophosphate (cAMP) signaling drive
      SOCS3 expression in inactive ulcerative colitis.
AB  - Ulcerative colitis (UC) is a chronic disease associated with long periods of
      quiescent disease followed by fulminant exacerbation. Imminent relapse in UC is
      associated with high mucosal expression of suppressor of cytokine signaling 3
      (SOCS3); hence, knowledge of the mechanisms driving mucosal SOCS3 expression may
      provide important clues as to rational therapy. Thus, here we aim to characterize
      the molecular forces driving SOCS3 expression in the mucosal compartment,
      focusing on druggable pathways. The colon epithelial cell line Caco-2 was
      stimulated with interferon (IFN)-gamma, interleukin (IL)-4 or prostaglandin E(2)
      (PGE(2)) to allow correlations between SOCS3 expression with signal transducer
      and activator of transcription 1 (STAT1), STAT6 and adenosine 3',5'-cyclic
      monophosphate (cAMP) signaling, respectively. The physiological relevance of the
      findings obtained was assessed by immunohistochemical staining for the activated
      forms of STAT1, STAT6, protein kinase A (PKA)-Cgamma and cAMP response element
      binding protein (CREB) in biopsies from inactive UC patients and controls.
      Stimulation with IFN-gamma, IL-4 or PGE(2) induced activation of STAT1, STAT6 and
      cAMP, respectively, in colonic cells, without any signs of concomitant STAT3
      activation. Forced activation of all these signaling pathways was sufficient for
      SOCS3 expression. Biopsies from patients with inactive UC showed significant
      increase of phosphorylated STAT1 (p-STAT1) (p < 0.0001), p-STAT6 (p = 0.0001), p
      PKA-Cgamma (p = 0.0003) and p-CREB (p = 0.0025) expression compared with
      controls. STAT3-independent SOCS3 induction in inactive UC involves multiple
      proinflammatory signaling pathways and contradicts the usefulness of pathway
      specific antiinflammatory drugs for preventing relapse. Our findings suggest that
      broad-spectrum antiinflammatory drugs are essential to counteract increases in
      SOCS3 expression and exacerbation of disease. Our results highlight the
      multifactorial nature of the factors that cause exacerbation in UC.

PMID- 23154641
TI  - Quantitative carbon ion beam radiography and tomography with a flat-panel
      detector.
AB  - High dose gradients are inherent to ion beam therapy. This results in high
      sensitivity to discrepancies between planned and delivered dose distributions.
      Therefore an accurate knowledge of the ion stopping power of the traversed tissue
      is critical. One proposed method to ensure high quality dose deposition is to
      measure the stopping power by ion radiography. Although the idea of imaging with
      highly energetic ions is more than forty years old, there is a lack of simple
      detectors suitable for this purpose. In this study the performance of an
      amorphous silicon flat-panel detector, originally designed for photon imaging,
      was investigated for quantitative carbon ion radiography and tomography. The flat
      panel detector was exploited to measure the water equivalent thickness (WET) and
      water equivalent path length (WEPL) of a phantom at the Heidelberg Ion-Beam
      Therapy Center (HIT). To do so, the ambiguous correlation of detector signal to
      particle energy was overcome by active or passive variation of carbon ion beam
      energy and measurement of the signal-to-beam energy correlation. The active
      method enables one to determine the WET of the imaged object with an uncertainty
      of 0.5 mm WET. For tomographic WEPL measurements the passive method was exploited
      resulting in an accuracy of 0.01 WEPL. The developed imaging technique presents a
      method to measure the two-dimensional maps of WET and WEPL of phantoms with a
      simple and commercially available detector. High spatial resolution of 0.8 * 0.8
      mm(2) is given by the detector design. In the future this powerful tool will be
      used to evaluate the performance of the treatment planning algorithm by studying
      WET uncertainties.

PMID- 23154642
TI  - The predictive significance of neurocognitive factors for functional outcome in
      bipolar disorder.
AB  - PURPOSE OF REVIEW: Poor psychosocial functioning in bipolar disorder often
      persists even after affective symptom remission. Cognitive deficits, which have
      emerged as a core feature of bipolar disorder in the past few years, are among
      the factors implicated in adverse psychosocial outcomes of patients suffering
      from bipolar disorder. This review aims to overview recent literature on the
      association of neurocognition and psychosocial functioning in bipolar disorder.
      RECENT FINDINGS: Cognitive deficits (mainly general neurocognitive functioning,
      attention and verbal learning and memory) are important determinants of poor
      psychosocial functioning in bipolar disorder, although to a lesser extent than in
      schizophrenia. Although affective symptoms appear to be a more important
      predictor of functional outcome in symptomatic patients, cognitive deficits also
      play a significant role, more readily recognizable in euthymic or chronic
      patients. SUMMARY: Given the importance of cognitive impairments for psychosocial
      outcomes in bipolar disorder, the development of interventions targeting
      cognitive impairments is imperative for improving recovery rates and quality of
      life in patients, even after adequate symptom control.

PMID- 23154643
TI  - Novel biomarkers in major depression.
AB  - PURPOSE OF REVIEW: This article reviews literature published over the period
      January 2011-June 2012 on biomarkers in major depression. RECENT FINDINGS:
      Although a large body of research accumulated over the past decades points to
      distinct biological mechanisms being involved in the pathophysiology of major
      depressive disorder (MDD), its precise pathobiology is not yet fully understood.
      In the last 2 years, substantial new research has been generated in an attempt to
      identify and characterize novel candidate biomarkers for MDD. This review
      provides an update on biomarker research in MDD and summarizes the most recent
      results from neuroimaging, genetic, epigenetic, and neurochemical studies in MDD.
      SUMMARY: Promising new findings report high diagnostic accuracy for metabonomic
      and epigenetic approaches as well as combinatorial functional neuroimaging
      approaches, which are currently representing the forefront of MDD biomarker
      development.

PMID- 23154645
TI  - Complex posttraumatic stress disorder and survivors of human rights violations.
AB  - PURPOSE OF REVIEW: This article reviews recent findings on Complex Posttraumatic
      Stress Disorder (CPTSD) and proposes future research which would help to
      establish the nature of CPTSD in relation to Posttraumatic Stress Disorder
      (PTSD). RECENT FINDINGS: Research on survivors of torture and war has found that
      CPTSD can occur when there is no history of childhood abuse. fMRI studies appear
      to highlight differences in neural activity in individuals exhibiting primary
      dissociation compared with individuals exhibiting secondary dissociation.
      Research has begun to show that, when symptoms of secondary dissociation are
      appropriately managed, exposure-based therapies are an effective treatment for
      individuals with CPTSD. SUMMARY: Much research on CPTSD has emphasized its
      developmental basis and the disruptive effects of trauma in childhood and
      adolescence on subsequent emotional development. However, some studies on
      survivors of torture in adult life identify similar symptom patterns, despite
      there being no history of childhood trauma. It is argued that comparative
      research is required between victims of developmental trauma (such as childhood
      sexual abuse) and victims who experienced prolonged interpersonal trauma in
      adulthood (such as torture), as this could be useful in establishing the cause of
      CPTSD and in delineating clinically and therapeutically meaningful subtypes. It
      is also proposed that a focus on underlying neurobiological processes would help
      in developing and refining CPTSD as a construct and informing treatment.

PMID- 23154644
TI  - The expanding evidence base for rTMS treatment of depression.
AB  - PURPOSE OF REVIEW: Daily left prefrontal transcranial magnetic stimulation (TMS)
      for several weeks was first proposed as an acute treatment for depression in the
      early 1990s, and was Food and Drug Administration (FDA) approved in 2008. In the
      past year, several important studies have been published that extend our
      understanding of this novel treatment approach. RECENT FINDINGS: The first round
      of multisite clinical trials with TMS addressed whether prefrontal rTMS has
      efficacy and were conducted in carefully selected depressed patients who were
      antidepressant medication free. Several more recent studies assess the clinical
      effectiveness of TMS and report that about 35-40% of real-world patients who are
      commonly taking adjunctive antidepressants reach remission with a modest side
      effect profile. There are also new studies examining the durability of the TMS
      induced antidepressant effect. Fifty-eight percent of TMS remitters remain
      remitted at 3-month follow-up. SUMMARY: These recent studies suggest that daily
      left prefrontal TMS over several weeks as a treatment for depression not only
      appears to have efficacy in rigorous randomized controlled trials, but is
      effective in real-world settings, with remission in 30-40% of patients. The TMS
      antidepressant effect, once achieved, appears to be as durable as with other
      antidepressant medications or interventions. Much more research is needed,
      particularly with issues such as the TMS coil location, stimulation intensity and
      frequency, and dosing strategy.

PMID- 23154646
TI  - Identification of pediatric brain neoplasms using Raman spectroscopy.
AB  - PURPOSE: Raman spectroscopy can quickly and accurately diagnose tissue in near
      real-time. This study evaluated the capacity of Raman spectroscopy to diagnose
      pediatric brain tumors. EXPERIMENTAL DESIGN: Samples of untreated pediatric
      medulloblastoma (4 samples and 4 patients), glioma (i.e. astrocytoma,
      oligodendroglioma, ependymoma, ganglioglioma and other gliomas; 27 samples and 19
      patients), and normal brain samples (33 samples and 5 patients) were collected
      fresh from the operating room or from our frozen tumor bank. Samples were divided
      and tested using routine pathology and Raman spectroscopy. Twelve Raman spectra
      were collected per sample. Support vector machine analysis was used to classify
      spectra using the pathology diagnosis as the gold standard. RESULTS: Normal brain
      (321 spectra), glioma (246 spectra) and medulloblastoma (82 spectra) were
      identified with 96.9, 96.7 and 93.9% accuracy, respectively, when compared with
      each other. High-grade ependymomas (41 spectra) were differentiated from low
      grade ependymomas (25 spectra) with 100% sensitivity and 96.0% specificity.
      Normal brain tissue was distinguished from low-grade glioma (118 spectra) with
      91.5% sensitivity and 97.8% specificity. For these analyses, the tissue-level
      classification was determined to be 100% accurate. CONCLUSION: These results
      suggest Raman spectroscopy can accurately distinguish pediatric brain neoplasms
      from normal brain tissue, similar tumor types from each other and high-grade from
      low-grade tumors.

PMID- 23154647
TI  - Towards a personalized and dynamic CRT-D. A computational cardiovascular model
      dedicated to therapy optimization.
AB  - BACKGROUND: In spite of cardiac resynchronization therapy (CRT) benefits, 25-30%
      of patients are still non responders. One of the possible reasons could be the
      non optimal atrioventricular (AV) and interventricular (VV) intervals settings.
      Our aim was to exploit a numerical model of cardiovascular system for AV and VV
      intervals optimization in CRT. METHODS: A numerical model of the cardiovascular
      system CRT-dedicated was previously developed. Echocardiographic parameters,
      Systemic aortic pressure and ECG were collected in 20 consecutive patients before
      and after CRT. Patient data were simulated by the model that was used to optimize
      and set into the device the intervals at the baseline and at the follow up. The
      optimal AV and VV intervals were chosen to optimize the simulated selected
      variable/s on the base of both echocardiographic and electrocardiographic
      parameters. RESULTS: Intervals were different for each patient and in most cases,
      they changed at follow up. The model can well reproduce clinical data as verified
      with Bland Altman analysis and T-test (p > 0.05). Left ventricular remodeling was
      38.7% and left ventricular ejection fraction increasing was 11% against the 15%
      and 6% reported in literature, respectively. CONCLUSIONS: The developed numerical
      model could reproduce patients conditions at the baseline and at the follow up
      including the CRT effects. The model could be used to optimize AV and VV
      intervals at the baseline and at the follow up realizing a personalized and
      dynamic CRT. A patient tailored CRT could improve patients outcome in comparison
      to literature data.

PMID- 23154648
TI  - Associations of proteinuria, fluid volume imbalance, and body mass index with
      circadian ambulatory blood pressure in chronic kidney disease patients.
AB  - BACKGROUND/AIMS: Obesity and hypervolemic status are the main causes of
      hypertension in patients with chronic kidney disease (CKD). However, it is
      difficult to differentiate between them. We aimed to assess the associations of
      body mass index (BMI) and total body water (TBW) with ambulatory blood pressure
      (ABP). METHODS: Body composition by bioelectrical impedance analysis (BIA) and 24
      h ABP were measured in 40 patients with CKD. TBW was assessed using corrected
      TBWBIA adjusted for body surface area (cTBWBIA) and the TBWBIA/TBWWatson ratio
      obtained using an anthropometric formula (Watson). RESULTS: Elevated ABP (average
      24-h BP >= 135/85 mmHg) was noted in 23 patients, who were more likely to have a
      higher cTBWBIA and TBWBIA/TBWWatson ratio than patients without elevated BP.
      Patients with nocturnal non-dipping (<10% drop in BP during sleep) were more
      likely to have a higher TBWBIA/TBWWatson ratio. Proteinuria and the
      TBWBIA/TBWWatson ratio were significant independent factors for 24-h ABP. BMI had
      a positive correlation with the cTBWBIA, TBWBIA/TBWWatson ratio and furosemide
      use. CONCLUSION: Hypertension is dependent on proteinuria and fluid volume
      imbalance. The TBWBIA/TBWWatson ratio can serve as an indicator of fluid volume
      dependent hypertension. BMI is affected by TBW, in which case BMI can become less
      involved with 24-h ABP.

PMID- 23154649
TI  - How I would manage a man with COPD who has few symptoms and is at low risk of an
      exacerbation: a primary care perspective from Australia.

PMID- 23154650
TI  - How I would manage a woman with COPD who is symptomatic but at low risk of an
      exacerbation: a primary care perspective from the UK.

PMID- 23154651
TI  - How I would manage a woman with COPD with few symptoms but at high risk of an
      exacerbation: a primary care perspective from Spain.

PMID- 23154652
TI  - How I would manage a man with COPD who is symptomatic  and at high risk of an
      exacerbation: a primary care  perspective from Norway.

PMID- 23154653
TI  - Serologic screening for herpes simplex virus type 2 in persons with human
      immunodeficiency virus.
AB  - Screening for subclinical herpes simplex virus type 2 (HSV-2) may be a useful
      adjunct in human immunodeficiency virus (HIV) care. However, HSV-2 serological
      tests have been suggested to perform less well in HIV-infected populations. In
      this study, HerpeSelect HSV-2 ELISA was compared with the Sure-Vue Rapid HSV-2
      Test for HSV-2 screening of sera from 310 HIV-infected persons receiving care at
      an HIV-dedicated clinic in the Southeastern United States. In the study, assay
      agreement and whether the performance of both tests, rather than 1 test alone,
      would improve screening accuracy were determined. Overall percent test agreement
      was 96%. Negative percent agreement was best at a HerpeSelect index value <0.90
      and positive percent agreement was best at a HerpeSelect index value >=3.0 (97%
      and 100%, respectively). Using the manufacturer's established cutoffs for a
      HerpeSelect positive test result versus negative test result, discordant results
      between assays occurred in 4% of the cases, and the majority of these cases
      occurred when the HerpeSelect index value was between 0.9 and 2.9. These data
      suggest a good correlation between the HerpeSelect and the Sure-Vue HSV-2 Rapid
      Test in a U.S. HIV-infected population and suggest that confirmatory testing may
      not help in HSV-2 diagnosis except in cases where HerpeSelect index values are
      between 0.9 and 3.0.

PMID- 23154654
TI  - Management of elderly and frail elderly cancer patients: the importance of
      comprehensive geriatrics assessment and the need for guidelines.
AB  - OBJECTIVES: Management of elderly and frail patients with cancer is complex and
      requires a multidisciplinary approach. This article reviews and discusses the
      current literature that evaluates the relevance of comprehensive geriatrics
      assessment (CGA) and other evaluation tools in the detection of this vulnerable
      patient population. METHODS: A literature search of articles in English, Spanish
      and Portuguese was conducted in PubMed through September 2011. RESULTS: There is
      lack of detailed information concerning the efficacy, tolerability and toxicity
      of cancer therapies in senior adults, although the literature indicates that
      there is a trend toward including elderly patients and their outcome. Recent
      guidelines advocate a careful patient selection through a CGA. For vulnerable
      (pre-frail) and frail elderly cancer patients, there is no consensus in relation
      to selection and type of treatments. CGA has been advocated as the gold standard
      for evaluation of elderly patients, but thorough evaluation of vulnerable and
      frail patients has not been undertaken. A tool to evaluate vulnerable elderly
      patients to predict treatment outcomes is also needed. DISCUSSION: The adoption
      of the CGA in oncology practice has been slow because of the difficulties with
      practicality and objectivity. A shorter reliable tool for rapid and complete
      assessment is needed. Inclusion of frail elderly patients in treatment trials is
      recommended. New treatment approaches for frail elderly cancer patients need to
      be further investigated. Some studies that used serum markers of frailty found
      that even in the absence of clinical signs, some elderly patients might be
      already vulnerable. A potential cancer frailty index also needs further
      investigation.

PMID- 23154655
TI  - Statin-mediated low-density lipoprotein lowering in chronic congestive heart
      failure.
AB  - Many theories and clinical trials have attempted to address the effect of low
      density lipoprotein (LDL) lowering in chronic congestive heart failure (CHF). The
      current evidence suggests that there is no convincing reason for administering
      statins to patients with nonischemic heart failure. Although they do not reduce
      the mortality rate, statins reduce LDL cholesterol and may provide some benefit
      to patients with ischemic heart failure. In contrast, some authors believe that
      statin therapy may actually worsen outcomes in patients with CHF, especially if
      there is excessive reduction in LDL cholesterol. This review discusses the
      theories attempting to link the adverse effects of statin-mediated LDL lowering
      in CHF to increased levels of endotoxin or reduced levels of coenzyme Q10. In
      addition, the 2 largest randomized, double-blind, placebo-controlled clinical
      trials (CORONA and GISSI-HF) were discussed. It is clear that more trials are
      needed to definitely ascertain the effect of statins on CHF.

PMID- 23154656
TI  - New evidence of neuroprotection by lactate after transient focal cerebral
      ischaemia: extended benefit after intracerebroventricular injection and efficacy
      of intravenous administration.
AB  - BACKGROUND: Lactate protects mice against the ischaemic damage resulting from
      transient middle cerebral artery occlusion (MCAO) when administered
      intracerebroventricularly at reperfusion, yielding smaller lesion sizes and a
      better neurological outcome 48 h after ischaemia. We have now tested whether the
      beneficial effect of lactate is long-lasting and if lactate can be administered
      intravenously. METHODS: Male ICR-CD1 mice were subjected to 15-min suture MCAO
      under xylazine + ketamine anaesthesia. Na L-lactate (2 ul of 100 mmol/l) or
      vehicle was administered intracerebroventricularly at reperfusion. The
      neurological deficit was evaluated using a composite deficit score based on the
      neurological score, the rotarod test and the beam walking test. Mice were
      sacrificed at 14 days. In a second set of experiments, Na L-lactate (1 umol/g
      body weight) was administered intravenously into the tail vein at reperfusion.
      The neurological deficit and the lesion volume were measured at 48 h. RESULTS:
      Intracerebroventricularly injected lactate induced sustained neuroprotection
      shown by smaller neurological deficits at 7 days (median = 0, min = 0, max = 3, n
      = 7 vs. median = 2, min = 1, max = 4.5, n = 5, p < 0.05) and 14 days after
      ischaemia (median = 0, min = 0, max = 3, n = 7 vs. median = 3, min = 0.5, max =
      3, n = 7, p = 0.05). Reduced tissue damage was demonstrated by attenuated
      hemispheric atrophy at 14 days (1.3 +/- 4.0 mm(3), n = 7 vs. 12.1 +/- 3.8 mm(3),
      n = 5, p < 0.05) in lactate-treated animals. Systemic intravenous lactate
      administration was also neuroprotective and attenuated the deficit (median = 1,
      min = 0, max = 2.5, n = 12) compared to vehicle treatment (median = 1.5, min = 1,
      max = 8, n = 12, p < 0.05) as well as the lesion volume at 48 h (13.7 +/- 12.2
      mm(3), n = 12 vs. 29.6 +/- 25.4 mm(3), n = 12, p < 0.05). CONCLUSIONS: The
      beneficial effect of lactate is long-lasting: lactate protects the mouse brain
      against ischaemic damage when supplied intracerebroventricularly during
      reperfusion with behavioural and histological benefits persisting 2 weeks after
      ischaemia. Importantly, lactate also protects after systemic intravenous
      administration, a more suitable route of administration in a clinical emergency
      setting. These findings provide further steps to bring this physiological,
      commonly available and inexpensive neuroprotectant closer to clinical translation
      for stroke.

PMID- 23154657
TI  - Ferromagnetic coupling and spin canting behaviour in heterobimetallic
      Re(IV)M(II/III) (M = Co(II/III), Ni(II)) species.
AB  - Three novel heterobimetallic Re(IV) compounds of formulae [ReBr(4)(MU-ox)M(4,7
      Cl(2)phen)(2)].CH(3)CN.CH(3)NO(2) [M = Co(II) (1) and Ni(II) (2)] and
      [ReBr(4)(ox)](3)[Co(III)(5,6-dmphen)(3)](2).CH(3)CN.2CH(3)NO(2).4H(2)O (3) [ox =
      oxalate, 4,7-Cl(2)phen = 4,7-dichloro-1,10-phenanthroline and 5,6-dmphen = 5,6
      dimethyl-1,10-phenanthroline] have been synthesised and the structures of 1 and 3
      determined by single crystal X-ray diffraction. Compound 1 is an oxalato-bridged
      Re(IV)Co(II) heterodinuclear complex where the [ReBr(4)(ox)](2-) unit acts as a
      bidentate ligand towards the [Co(4,7-Cl(2)phen)(2)](2+) entity, the separation
      between Re(IV) and Co(II) across the oxalate being 5.482(1) A. Compound 3 is an
      ionic salt whose structure is made up of [Re(IV)Br(4)(ox)](2-) anions and
      [Co(III)(5,6-dmphen)(3)](3+) cations plus acetonitrile, nitromethane and water as
      solvent molecules. The magnetic properties of 1-3 were investigated in the
      temperature range 1.9-300 K. Relatively large ferromagnetic interactions between
      Re(IV) and M(II) through the bis(bidentate) oxalato occur in 1 and 2 [J(ReM) =
      +11.0 (1) and +12.2 cm(-1) (2), the Hamiltonian being defined as H = 
      J(ReM)S(Re).S(M)] which are explained on the basis of orbital symmetry
      considerations. A behaviour typical of a magnetically diluted Re(IV) complex with
      a large and positive value of zero-field splitting for the ground level (D(Re) =
      +43 cm(-1)) is observed for 3 in the high temperature range, whereas it exhibits
      spin canting in the low temperature domain as well as magnetic ordering below ca.
      4.8 K.

PMID- 23154658
TI  - Correlative studies on the effects of obesity, diabetes and hypertension on gene
      expression in omental adipose tissue of obese women.
AB  - OBJECTIVE: A major consequence of obesity is the enormous expansion of and
      enhanced inflammatory response seen in visceral adipose tissue. I hypothesized
      that the expression of inflammatory markers in visceral omental fat would
      correlate with the extent of visceral adiposity as measured by waist
      circumference or body mass index and that diabetes and hypertension, defined as
      subjects taking anti-hypertensive drugs, would be associated with changes in mRNA
      expression in visceral fat. DESIGN AND METHODS: The expression of 106 mRNAs by RT
      PCR was examined in observational studies using extracts of omental fat of obese
      women undergoing bariatric surgery as well as the circulating levels of some
      adipokines. We also compared the mRNA levels of 65 proteins in omental fat
      removed during gastric bypass surgery of women with and without hypertension and
      those with type 2 diabetes. RESULTS: Out of 106 mRNAs the expression of 10 mRNAs
      in omental fat of women not taking anti-hypertensive drugs correlated with waist
      circumference while 7 different mRNAs had significant correlations with
      circulating glucose. The correlations of waist circumference with mRNA expression
      were abolished, except for interleukin (IL)-1 receptor antagonist (IL-1RA), in
      women taking anti-hypertensive drugs. The correlations of blood glucose with
      omental fat mRNA expression were abolished, except for that of Akt1 and Akt2, in
      women taking anti-hypertensive drugs. However, the expression of 4 different
      mRNAs in omental fat was affected by circulating glucose in subjects taking anti
      hypertensive drugs. The circulating levels of IL-1 RA, but not fatty acid binding
      protein 4, adipsin and phospholipase A2, correlated with both waist circumference
      and mRNA expression in omental fat. CONCLUSION: In female bariatric surgery
      patients, the mRNA expression of some proteins in omental fat was affected by the
      degree of obesity, whereas hypertension and diabetes affected a separate set of
      mRNAs.Nutrition and Diabetes (2011) 1, e17; doi:10.1038/nutd.2011.14; published
      online 26 September 2011.

PMID- 23154659
TI  - Qualitative analysis of naturalistic decision making in adults with chronic heart
      failure.
AB  - BACKGROUND: Self-care of heart failure has been described as a naturalistic
      decision-making process, but the data available to defend this description are
      anecdotal. OBJECTIVES: The aim of this study was to explore the process used by
      adults with chronic heart failure to make decisions about their symptoms.
      METHODS: This was a secondary analysis of data obtained from four mixed methods
      studies. The full data set held qualitative data on 120 adults over the age of 18
      years. For this analysis, maximum variation sampling was used to purposively
      select a subset of 36 of the qualitative interviews to reanalyze. RESULTS: In
      this sample, equally distributed by gender, 56% Caucasian, between 40 and 98
      years, the overarching theme was that decisions about self-care reflect a
      naturalistic decision-making process with components of situation awareness with
      mental simulation of a plausible course of action and an evaluation of the
      outcome of the action. In addition to situation awareness and mental simulation,
      three key factors were identified as influencing self-care decision making: (a)
      experience; (b) decision characteristics such as uncertainty, ambiguity, high
      stakes, urgency, illness, and involvement of others in the decision-making
      process; and (c) personal goals. DISCUSSION: These results support naturalistic
      decision making as the process used by this sample of adults with heart failure
      to make decisions about self-care.

PMID- 23154660
TI  - Endothelial dysfunction, macrophage infiltration and NADPH oxidase-dependent
      superoxide production were attenuated by erythropoietin in streptozotocin-induced
      diabetic rat aorta.
AB  - Erythropoietin (EPO) has been used for the management of renal anemia. Recent
      studies suggest the pleiotropic properties of EPO in various tissues such as
      brain, kidney and vasculature. Diabetes mellitus is a major risk for development
      of vascular impairment. The aim of the present study was to investigate the
      hypothesis that EPO would be beneficial in inhibiting diabetic macroangiopathy.
      Recombinant human EPO (rHuEPO; 150 U/kg, 3 times/week, s.c.) was administered to
      streptozotocin-induced diabetic rats for 4 weeks. Streptozotocin (65 mg/kg, i.v.)
      significantly increased macrophage infiltration and adhesion molecules, monocyte
      chemoattractant protein-1 and osteopontin mRNA levels in the aorta. These
      inflammatory changes were suppressed by rHuEPO. Vasodilation in response to
      acetylcholine in the aortic ring was impaired in the diabetic rats, and improved
      by rHuEPO. rHuEPO inhibited the aortic expression of mRNA for nicotinamide
      adenine dinucleotide phosphate (NADPH) oxidase and the NADPH oxidase-dependent
      superoxide production and the increase in plasma malondialdehyde concentration in
      diabetic rats. rHuEPO also decreased the level of the receptor for advanced
      glycation end products in the aorta. We also found an increased expression of
      phospho-Akt and endothelial nitric oxide synthase and plasma NOx level in the
      rHuEPO-treated group. On the other hand, rHuEPO did not affect blood glucose
      levels, hemoglobin A(1c), blood pressure or hematocrit in diabetic rats. These
      results indicate that rHuEPO exerts pleiotropic antioxidant and anti-inflammatory
      properties in diabetic rat aorta.

PMID- 23154662
TI  - Ceramic gentamicin beads in vascular graft infection--a cautionary note.

PMID- 23154663
TI  - Hysteroscopic inspection and total curettage are insufficient for discriminating
      endometrial cancer from atypical endometrial hyperplasia.
AB  - Endometrial cancer (EC) is the most prevalent gynecologic malignancy in Japan. 
      Atypical endometrial hyperplasia (AEH) is viewed as the premalignant lesion of
      EC, however it is often difficult to distinguish EC from AEH.  The rate of
      concurrent EC in women diagnosed preoperatively with AEH based on endometrial
      biopsy was reported as 17-52%.  Although hysteroscopic inspection and total
      curettage are considered as useful methods to make diagnosis of endometrial
      lesions, there is no report using this combined method to discriminate EC from
      AEH.  The purpose of this study was to examine whether hysteroscopic inspection
      and total curettage improve the prevalence of EC among women diagnosed
      preoperatively with AEH.  We reviewed 22 patients who underwent hysteroscopic
      inspection and total curettage and were diagnosed with AEH before undergoing
      hysterectomy between November 2001 and May 2011.  The diagnosis made with the
      hysterectomy specimens revealed AEH in 10 patients (45.5%), endometrial
      hyperplasia without atypia in 3 (13.6%), and endometrioid adenocarcinoma, the
      most common type of EC, in 9 (40.9%).  Endometrioid adenocarcinoma included 7
      patients without myometrial invasion (31.8%) and 2 patients with superficial
      myometrial invasion (9.1%).  There was no hysteroscopic finding that was specific
      for EC or AEH.  In conclusion, about 41% of women who underwent hysterectomy
      under a diagnosis of AEH were found to have coexisting adenocarcinoma, although
      the prevalence of EC among those women was similar to that in earlier reports
      with endometrial biopsy.  Accordingly, we must be careful in planning the
      therapeutic strategy for women with a preoperative diagnosis of AEH.

PMID- 23154665
TI  - Current world literature.

PMID- 23154664
TI  - Experimental estimation of the photons visiting probability profiles in time
      resolved diffuse reflectance measurement.
AB  - A time-gated intensified CCD camera was applied for time-resolved imaging of
      light penetrating in an optically turbid medium. Spatial distributions of light
      penetration probability in the plane perpendicular to the axes of the source and
      the detector were determined at different source positions. Furthermore, visiting
      probability profiles of diffuse reflectance measurement were obtained by the
      convolution of the light penetration distributions recorded at different source
      positions. Experiments were carried out on homogeneous phantoms, more realistic
      two-layered tissue phantoms based on the human skull filled with Intralipid-ink
      solution and on cadavers. It was noted that the photons visiting probability
      profiles depend strongly on the source-detector separation, the delay between the
      laser pulse and the photons collection window and the complex tissue composition
      of the human head.

PMID- 23154667
TI  - Gold nanorod-covered kanamycin-loaded hollow SiO2 (HSKAu(rod)) nanocapsules for
      drug delivery and photothermal therapy on bacteria.
AB  - A hybrid bactericidal material, gold nanorod-covered kanamycin-loaded hollow
      SiO(2) (HSKAu(rod)) nanocapsules, is constructed. The hybrid material combines
      the features of a chemical drug with photothermal physical sterilization which
      decreases the dosage of broad-spectrum antibiotic and the physical damage of
      biological systems. Hollow SiO(2) nanocapsules are used as carriers for drug
      delivery. The nanocapsules load a model drug, kanamycin, and are covered with
      gold nanorods to avoid drug leakage and realize photothermal treatment. The
      sterilizing effect on the bacterial strain is investigated by incubating E. coli
      BL21 with the hybrid nanocapsules and irradiating under near-infrared light (NIR)
      for 20 min. A bactericidal effect, i.e., a sterilizing rate of 53.47%, is
      achieved for the HSKAu(rod) nanocapsules under NIR irradiation, with respect to a
      net sum sterilizing rate of 34.49% for the individual components of the
      HSKAu(rod) nanocapsules, e.g., carrier nanocapsules, chemical sterilization of
      kanamycin and physical sterilization due to the gold nanorods under NIR
      irradiation. It is demonstrated that the combination of chemical drug and
      physical sterilization results in an obvious synergistic effect and makes the
      sterilization more effective. This novel hybrid has great potential as an
      adjuvant therapeutic alternative material for sterilization or even for the
      control of disease.

PMID- 23154668
TI  - Medical thoracoscopy in multiloculated and organised empyema.

PMID- 23154669
TI  - Accuracy of signs of clinical chorioamnionitis in the term parturient.
AB  - OBJECTIVE: Uniform histopathologic guidelines were applied to diagnose
      chorioamnionitis and estimate the accuracy of clinical signs in term parturients.
      STUDY DESIGN: A retrospective cohort study utilized slides from term parturient
      placentas with Amniotic Fluid Infection Nosology Committee guidelines as the gold
      standard. Sensitivity, specificity and accuracy for fever, maternal tachycardia
      and fetal tachycardia were calculated. RESULT: Of 641 placentas, 367 (57.3%) had
      histologic chorioamnionitis and 274 (42.7%) were negative. Fever had a
      sensitivity of 42%, specificity of 86.5% and accuracy of 61%. Fever, maternal
      tachycardia and fetal tachycardia had a sensitivity of 18.3%, specificity of
      98.2% and accuracy of 52.4%. CONCLUSION: Histologic chorioamnionitis, frequently
      asymptomatic, is a common finding in placentas examined from term parturients.
      Clinical signs are not accurate in the diagnosis. Adoption of uniform pathologic
      guidelines will facilitate research into the clinical significance of these
      lesions in the future.

PMID- 23154670
TI  - Passive cooling during transport of asphyxiated term newborns.
AB  - OBJECTIVE: To evaluate the efficacy and safety of passive cooling during
      transport of asphyxiated newborns. STUDY DESIGN: Retrospective medical record
      review of newborns with perinatal asphyxia transported for hypothermia between
      July 2007 and June 2010. RESULT: Of 43 newborns transported, 27 were passively
      cooled without significant adverse events. Twenty (74%) passively cooled newborns
      arrived with temperature between 32.5 and 34.5  degrees C. One newborn arrived
      with a temperature <32.5, and 6 (22%) had temperatures >34.5  degrees C. Time
      from birth to hypothermia was significantly shorter among passively cooled
      newborns compared with newborns not cooled (215 vs 327 min, P<0.01), even though
      time from birth to admission to Boston Children's Hospital was similar (252 vs
      259 min, P=0.77). Time from birth to admission was the only significant predictor
      of increased time to reach target temperature (P=0.001). CONCLUSION: Exclusive
      passive cooling achieves significantly earlier initiation of effective
      hypothermia for asphyxiated newborns but should not delay transport for active
      cooling.

PMID- 23154671
TI  - Arthroscopic treatment of fragmented coronoid process with severe elbow
      incongruity. Long-term follow-up  in eight Bernese Mountain Dogs.
AB  - The purpose of this study was to investigate the long-term treatment results of
      fragmented coronoid process (FCP) in joints with a radio-ulnar step greater than
      3 mm. Treatment of these patients only consisted of fragment removal, without
      correction of the incongruity. The eight Bernese Mountain Dogs (11 joints)
      included in this study showed obvious clinical signs of elbow disease and were
      diagnosed with severe elbow incongruity and concomitant FCP in the time period
      from 1999-2003. At that time, elbow radiography, computed tomography, and
      arthroscopy were performed. The mean follow-up period was 5.6 years. The follow
      up consisted of a telephone questionnaire combined with a clinical and
      radiographic re-evaluation at our clinic. The questionnaire revealed that all
      dogs were either free of lameness or only lame following heavy exercise. One dog
      sporadically required medication after heavy exercise. The owner satisfaction
      rate was 100%. The clinical re-evaluation did not reveal any signs of pain or
      lameness in all cases. Range-of- motion was decreased in nine of the 11 elbows.
      Radiographs revealed an increase in severity of osteoarthritis in every case.In
      this case series, arthroscopic fragment removal without treatment of incongruity
      was demonstrated to be a valuable treatment option and may provide a satisfactory
      long-term outcome.

PMID- 23154672
TI  - VAP-1, a novel molecule linked to endothelial damage and kidney function in
      kidney allograft recipients.
AB  - BACKGROUND/AIMS: VAP-1 (vascular adhesion protein-1) is a copper-containing SSAO
      (semicarbazide sensitive amine oxidase) secreted by vascular smooth muscle cells,
      adipocytes, endothelial cells with functional monoamine oxidase activity. The
      oxidation process generates harmful products that may be involved in
      atherosclerosis and vascular damage. Elevation of SSAO activity is observed in
      atherosclerosis, diabetes mellitus and obesity. On the other hand, renalase, with
      possible monoamine oxidase activity, which breaks down catecholamines like SSAO,
      is also expressed in the endothelium as well as in the kidney. The aim of the
      study was to assess VAP-1 levels and its correlations with endothelial injury
      markers and renalase in 50 kidney allograft recipients. METHODS: Hemoglobin,
      urea, creatinine, rate were studied by standard laboratory method in the hospital
      central laboratory. We assessed markers of endothelial function/injury: vWF,
      thrombomodulin, ICAM, VCAM, CD40L, CD44, CD146, inflammation: hsCRP, and IL-6 and
      adipocytokines: leptin, adiponectin, visfatin, apelin with commercially available
      assays. RESULTS: The mean serum VAP-1 in Tx was significantly higher comparing to
      the control group. In kidney transplant recipients VAP-1 correlated with BMI
      (r=0.39, p<0.01), CD44 (r=0.27, p<0.05), hsCRP (r=0.28, p<0.05), serum creatinine
      (r=0.29, p<0.05), eGFR (CKD-EPI formula r=-0.27, p<0.05, MDRD r=-0.27,p<0.05,
      Cockcroft-Gault r=-0.35,p<0.01), serum urea (r=0.27, p<0.05), CD146 (r=0.49,
      p<0.001), CD40L (r=0.26, p<0.06), and renalase (r=0.34, p<0.05). In multiple
      regression analysis VAP-1 was predicted 80% by serum creatinine (beta value 0.33,
      p=0.01), and CD146 (beta value 43, p=0.0005). CONCLUSION: VAP-1, elevated in
      kidney transplant recipients, is predominantly dependent on endothelial damage
      and kidney function, which deteriorated with time after kidney transplantation.

PMID- 23154673
TI  - Increased incidence of cardiovascular disease: are low-carbohydrate-high-protein
      diets truly to blame?

PMID- 23154674
TI  - HIV consensus guideline recommends antiretroviral treatment regardless of CD4
      count, new regimens and possible regimen change for chronic low level viraemia.

PMID- 23154675
TI  - Creating a bio-hybrid signal transduction pathway: opening a new channel of
      communication between cells and machines.
AB  - Manipulation of signal transduction pathways presents a viable mechanism to
      interface cells with electronics. In this work, we present a two-step signal
      transduction pathway involving cellular and electronic transduction elements. In
      order to circumvent many of the conventional difficulties encountered when
      harnessing chemical signalling for the purpose of electronics communication,
      gaseous nitric oxide (NO) was selected as the signalling molecule. By genetic
      engineering of the nitric oxide synthase protein eNOS and insertion of light
      oxygen-voltage (LOV) domains, we have created a photoactive version of the
      protein. The novel chimeric eNOS was found to be capable of producing NO in
      response to excitation by visible light. By coupling these mutant cells to a
      surface modified platinum electrode, it was possible to convert an optical signal
      into a chemical one, followed by subsequent conversion of the chemical signal
      into an electrical output.

PMID- 23154676
TI  - Staffing matters-every shift: data from the Military Nursing Outcomes Database
      can be used to demonstrate that the right number and mix of nurses prevent
      errors.
AB  - OVERVIEW: Data from the Military Nursing Outcomes Database (MilNOD) project
      demonstrate that inadequately staffed shifts can increase the likelihood of
      adverse events, such as falls with injury, medication errors, and needlestick
      injuries to nurses. Such evidence can be used to show that it takes not only the
      right number of nursing staff on every shift to ensure safe patient care, but
      also the right mix of expertise and experience. Based on findings from the MilNOD
      project, the authors present realistic scenarios of common dilemmas hospitals
      face in nurse staffing, illustrating the potential hazards for patients and
      nurses alike.

PMID- 23154677
TI  - Missing incidents in community-dwelling people with dementia: understanding how
      these dangerous events differ from dementia-related 'wandering' is critical to
      assessment, intervention, and prevention.
AB  - OVERVIEW: At every stage of dementia, people with the condition are at risk for
      both missing incidents, in which they are unattended and unable to navigate a
      safe return to their caregiver, and "wandering," a term often used to describe
      repetitive locomotion with patterns such as lapping or pacing. By understanding
      the differences between these two phenomena, nurses can teach caregivers how to
      anticipate and prevent missing incidents, which are not necessarily related to
      wandering. The authors differentiate missing incidents from wandering, describe
      personal characteristics that may influence the outcomes in missing incidents,
      and suggest strategies for preventing and responding to missing incidents.

PMID- 23154678
TI  - Secondary spacer modulated assembly of polyoxometalate based metal-organic
      frameworks.
AB  - To investigate the influence of a secondary spacer on the resulting structures of
      POMOFs containing pytz, five new compounds with different dimensionalities,
      [Cu(5)(2-pytz)(6)(H(2)O)(4)][SiMo(12)O(40)].3H(2)O (1), [Cu(3)(2
      pytz)(4)bipy][H(2)SiMo(12)O(40)].bipy (2), [Cu(3)(2
      pytz)(2)(bipy)(4)(H(2)O)(6)][H(4)SiW(12)O(40)](2).6H(2)O (3), [Cu(2)(2
      pytz)(phen)(OH)](2)[SiW(12)O(40)].H(2)O (4), [Cu(3)(4
      pytz)(4)(H(2)O)(4)][H(2)SiW(12)O(40)].2H(2)O (5), were synthesized. When only 2
      pytz was employed, compound 1 with a 3D framework was obtained, whereas when the
      secondary spacers (4,4'-bipy, phen and 4-pytz) were introduced into the reaction
      system of 1, compounds 2-5 were obtained and exhibit a broad range of structures,
      including 0D, 1D, 2D and 3D frameworks. It can be observed from the architectures
      of compounds 1-5 that the secondary spacers have a great effect on the structures
      of the MOFs, which results in the formation of various dimensional POMOF
      compounds. Additionally, photocatalytic experiments of 1-5 for the photocatalytic
      degradation of RhB under UV irradiation were also investigated.

PMID- 23154679
TI  - Stearic acid content of abdominal adipose tissues in obese women.
AB  - OBJECTIVE: Subcutaneous (SC) adipose tissue stearic acid (18:0) content and
      stearoyl-CoA desaturase-1 (SCD1)-mediated production of oleic acid (18:1) have
      been suggested to be altered in obesity. The objective of our study was to
      examine abdominal adipose tissue fatty acid content and SCD1 mRNA/protein level
      in women. SUBJECTS AND METHODS: Fatty acid content was determined by capillary
      gas chromatography in SC and omental (OM) fat tissues from two subgroups of 10
      women with either small or large OM adipocytes. Samples from 10 additional women
      were used to measure SCD1 mRNA and protein expression, total extracellular signal
      regulated kinase 1/2 (ERK1/2) and phosphorylated ERK1/2 protein as well as
      insulin receptor (IR) expression levels. RESULTS: OM fat 18:0 content was
      significantly lower in women with large OM adipocytes compared with women who had
      similar adiposity, but small OM adipocytes (2.37+/-0.45 vs 2.75+/-0.30 mg per 100
      g adipose tissue, respectively, P?0.05). OM fat 18:0 content was negatively
      related to the visceral adipose tissue area (r=-0.44, P=0.05) and serum
      triglyceride levels (r=-0.56, P<0.05), while SC fat 18:0 content was negatively
      correlated with total body fat mass (BFM) (r=-0.48, P<0.05) and fasting insulin
      concentration (r=-0.73, P<0.005). SC adipose tissue desaturation index
      (18:1/18:0), SCD1 expression and protein levels were positively correlated with
      BFM. Moreover, obese women were characterized by a reduced OM/SC ratio of SCD1
      mRNA and protein levels. A similar pattern was observed for ERK1/2 and IR
      expression. CONCLUSION: The presence of large adipocytes and increased adipose
      mass in a given fat compartment is related to reduced 18:0 content and increased
      desaturation index in women, independently of dietary fat intake. The depot
      specific difference in ERK1/2 expression and activation, as well as in SCD1 and
      IR expression in obese women is consistent with the hypothesis that they may
      predominantly develop SC fat, which could in turn help protect from metabolic
      disorders.

PMID- 23154680
TI  - Proximal correlates of metabolic phenotypes during 'at-risk' and 'case' stages of
      the metabolic disease continuum.
AB  - OBJECTIVE: To examine the social and behavioural correlates of metabolic
      phenotypes during 'at-risk' and 'case' stages of the metabolic disease continuum.
      DESIGN: Cross-sectional study of a random population sample. PARTICIPANTS: A
      total of 718 community-dwelling adults (57% female), aged 18-92 years from a
      regional South Australian city. MEASUREMENTS: Total body fat and lean mass and
      abdominal fat mass were assessed by dual energy x-ray absorptiometry. Fasting
      venous blood was collected in the morning for assessment of glycated haemoglobin,
      plasma glucose, serum triglycerides, cholesterol lipoproteins and insulin. Seated
      blood pressure (BP) was measured. Physical activity and smoking, alcohol and diet
      (96-item food frequency), sleep duration and frequency of sleep disordered
      breathing (SDB) symptoms, and family history of cardiometabolic disease,
      education, lifetime occupation and household income were assessed by
      questionnaire. Current medications were determined by clinical inventory.
      RESULTS: 36.5% were pharmacologically managed for a metabolic risk factor or had
      known diabetes ('cases'), otherwise were classified as the 'at-risk' population.
      In both 'at-risk' and 'cases', four major metabolic phenotypes were identified
      using principal components analysis that explained over 77% of the metabolic
      variance between people: fat mass/insulinemia (FMI); BP; lipidaemia/lean mass
      (LLM) and glycaemia (GLY). The BP phenotype was uncorrelated with other
      phenotypes in 'cases', whereas all phenotypes were inter-correlated in the 'at
      risk'. Over and above other socioeconomic and behavioural factors, medications
      were the dominant correlates of all phenotypes in 'cases' and SDB symptom
      frequency was most strongly associated with FMI, LLM and GLY phenotypes in the
      'at-risk'. CONCLUSION: Previous research has shown FMI, LLM and GLY phenotypes to
      be most strongly predictive of diabetes development. Reducing SDB symptom
      frequency and optimising the duration of sleep may be important concomitant
      interventions to standard diabetes risk reduction interventions. Prospective
      studies are required to examine this hypothesis.

PMID- 23154681
TI  - Abdominal adiposity and daily step counts as determinants of glycemic control in
      a cohort of patients with type 2 diabetes mellitus.
AB  - OBJECTIVE: Favorable effects of walking levels on glycemic control have been
      hypothesized to be mediated through reductions in abdominal adiposity, but this
      has not been well studied. We addressed this issue in patients treated for type 2
      diabetes. DESIGN: Cross-sectional analysis. SUBJECTS: A total of 201 subjects
      with type 2 diabetes underwent assessments of pedometer-measured daily step
      counts, blood pressure, A1C and anthropometric measures (2006-2010). Associations
      of anthropometric indicators of abdominal adiposity (that is, waist
      circumference; waist-to-hip ratio (WHR)) with A1C were evaluated through linear
      regression models adjusting for age, ethnicity, sex and the use of insulin and
      oral hypoglycemic agents. Models including waist circumference were additionally
      adjusted for body mass index (BMI). A similar approach was used to examine A1C
      and daily step associations. RESULTS: Among the 190 subjects (mean age 60 years;
      mean BMI 30.4 kg m(-2)), mean values (s.d.) for waist circumference and WHR were
      respectively, 99.1 cm (13.3) and 0.88 (0.07) in women, and 104.5 cm (13.1) and
      0.97 (0.06) in men. Mean A1C and daily step count were respectively, 7.6% (1.4)
      and 5 338 steps per day (2609), and were similar for both sexes.There was a 0.51%
      (95% confidence interval (CI): 0.10, 0.93) A1C increment per s.d. increase in
      waist circumference and a 0.32% (95% CI: 0.08, 0.56) A1C increment per s.d.
      increase in WHR in fully adjusted models. Each s.d. increase in daily step count
      was associated with clinically significant reductions in waist circumference and
      BMI. Each s.d. increase in daily steps was associated with a 0.21% (95% CI: 0.02,
      0.41) A1C decrement that declined to 0.16% (95% CI: -0.35, 0.04) with further
      adjustment for anthropometric indicators of abdominal adiposity. CONCLUSION:
      Higher daily steps may be associated with lower A1C values both directly and via
      changes in abdominal adiposity.

PMID- 23154683
TI  - Wheat-derived arabinoxylan oligosaccharides with prebiotic effect increase
      satietogenic gut peptides and reduce metabolic endotoxemia in diet-induced obese
      mice.
AB  - BACKGROUND: Alterations in the composition of gut microbiota -known as dysbiosis-
      have been proposed to contribute to the development of obesity, thereby
      supporting the potential interest of nutrients acting on the gut microbes to
      produce beneficial effect on host energetic metabolism. Non-digestible
      fermentable carbohydrates present in cereals may be interesting nutrients able to
      influence the gut microbiota composition. OBJECTIVE AND DESIGN: The aim of the
      present study was to test the prebiotic potency of arabinoxylan oligosaccharides
      (AXOS) prepared from wheat bran in a nutritional model of obesity, associated
      with a low-grade chronic systemic inflammation. Mice were fed either a control
      diet or a high fat (HF) diet, or a HF diet supplemented with AXOS during 8 weeks.
      RESULTS: AXOS supplementation induced caecal and colon enlargement associated
      with an important bifidogenic effect. It increased the level of circulating
      satietogenic peptides produced by the colon (peptide YY and glucagon-like peptide
      1), and coherently counteracted HF-induced body weight gain and fat mass
      development. HF-induced hyperinsulinemia and the Homeostasis Model Assessment of
      insulin resistance were decreased upon AXOS feeding. In addition, AXOS reduced HF
      induced metabolic endotoxemia, macrophage infiltration (mRNA of F4/80) in the
      adipose tissue and interleukin 6 (IL6) in the plasma. The tight junction proteins
      (zonula occludens 1 and claudin 3) altered upon HF feeding were upregulated by
      AXOS treatment suggesting that the lower inflammatory tone was associated with
      the improvement of gut barrier function. CONCLUSION: Together, these findings
      suggest that specific non-digestible carbohydrates produced from cereals such as
      AXOS constitute a promising prebiotic nutrient in the control of obesity and
      related metabolic disorders.

PMID- 23154684
TI  - Treating the small airways.
AB  - The final article in this series evaluates the approaches undertaken to treating
      the small-airway region of the lungs and the clinical implications of inhaled
      therapy targeting the periphery in patients with asthma and chronic obstructive
      pulmonary disease.

PMID- 23154685
TI  - Challenges in child and adolescent psychiatric education.

PMID- 23154682
TI  - Appetite regulation and weight control: the role of gut hormones.
AB  - The overwhelming increase in the prevalence of overweight and obesity in recent
      years represents one of the greatest threats to the health of the developed
      world. Among current treatments, however, gastrointestinal (GI) surgery remains
      the only approach capable of achieving significant weight loss results with long
      term sustainability. As the obesity prevalence approaches epidemic proportions,
      the necessity to unravel the mechanisms regulating appetite control has garnered
      significant attention. It is well known that physical activity and food intake
      regulation are the two most important factors involved in body weight control. To
      regulate food intake, the brain must alter appetite. With this realization has
      come increased efforts to understand the intricate interplay between gut hormones
      and the central nervous system, and the role of these peptides in food intake
      regulation through appetite modulation. This review discusses the central
      mechanisms involved in body weight regulation and explores a suite of well
      characterized and intensely investigated anorexigenic and orexigenic gut
      hormones. Their appetite-regulating capabilities, post-GI surgery physiology and
      emerging potential as anti-obesity therapeutics are then reviewed.

PMID- 23154686
TI  - Family therapy: the neglected core competence.

PMID- 23154687
TI  - Guidelines for the general psychiatry application process and for inter-residency
      transitions.

PMID- 23154688
TI  - Promoting scholarship during child and adolescent psychiatry residency.
AB  - BACKGROUND: In 2003, the Institute of Medicine (IOM) drew attention to the
      critical national shortage of psychiatrist-researchers and the need for
      competency-based curricula to promote research training during psychiatry
      residency as one way to address this shortage at the institutional level. Here,
      the authors report on the adaptation, implementation, and results attained with a
      broadly applicable, developmental, competency-based framework for promoting
      scholarship during child and adolescent psychiatry residency. METHODS: The
      authors instituted structural program changes, protecting time for all residents
      to engage in scholarly pursuits and a mentorship program to support residents in
      their scholarly interests. The authors assessed five graduating classes before
      and five classes after these changes were implemented, examining whether these
      changes sustained scholarship for residents with previous experience during
      general psychiatry residency and whether they promoted emergence of new
      scholarship among residents without such experience. RESULTS: The authors
      observed a tenfold increase in the number of residents engaged in rigorously
      defined scholarly pursuits after the program changes, which helped sustain the
      scholarship of more residents with previous experience and promoted the emergence
      of more new scholarship among residents without previous experience. CONCLUSION:
      The authors conclude that it is possible to sustain and promote scholarship
      during child psychiatry residency despite the relatively short duration of the
      program and the many requirements for graduation and certification. The changes
      implemented were universal in scope and required no special funding mechanisms,
      making this approach potentially exportable to other training programs.

PMID- 23154689
TI  - Family therapy training in child and adolescent psychiatry fellowship programs.
AB  - OBJECTIVE: This study describes the current state of family therapy training in a
      sample of child and adolescent psychiatry fellowship programs. METHOD: Child and
      adolescent psychiatry fellows (N=66) from seven training programs completed a
      questionnaire assessing demographics, family therapy training experiences, common
      models of treatment and supervision, attitudes about family therapy, and
      perspectives on clinical training and clinical skill. RESULTS: Fellows ascribed a
      high degree of importance to family therapy skills, yet most had not seen more
      than one outpatient family with family therapy supervision during their training.
      They identified structural family therapy and family psychoeducation as the
      primary family treatment orientations in their programs. CONCLUSION: Although
      child psychiatry fellows believed that strong family therapy skills would benefit
      their patients, most had limited supervised experiences with families. Child and
      adolescent psychiatry training programs appear to offer exposure to family
      therapy without sufficient opportunities to develop proficiency. The author
      discusses educational implications for child and adolescent psychiatry.

PMID- 23154690
TI  - Reflective team supervision after a frightening event on a psychiatric crisis
      service.
AB  - OBJECTIVE: The authors demonstrate the value of reflective team supervision as
      part of the informal curriculum in an emergency psychiatry setting after a
      potentially traumatizing adverse event. METHOD: The article gives a case
      presentation of a violent adolescent who eloped from his hospital Emergency
      Department and provides a description of team supervision sessions that
      facilitated informal learning for residents and medical students after this
      event. RESULTS: Reflective team supervision sessions after this event resulted
      both in improved resident well-being and learning opportunities, as well as
      hospital quality improvement designed to prevent future elopements. CONCLUSIONS:
      Reflective team supervision can be an essential component of trainee education to
      enhance residents' well-being and to promote both systems-based practice and
      practice-based learning. This can be an excellent forum to explore themes of
      humility, self-reflection, and professional growth.

PMID- 23154692
TI  - Medical students' comfort with pregnant women with substance-use disorders: a
      randomized educational study.
AB  - OBJECTIVE: The study objective was to determine whether medical students'
      attendance at a rehabilitation residence for pregnant women with substance-use
      disorders yielded changes in their attitudes and comfort levels in providing care
      to this population. METHODS: This randomized educational trial involved 96
      consecutive medical students during their obstetrics and gynecology clerkship. In
      addition to attending a half-day prenatal clinic designed for women with
      substance-use disorders, every student was randomly assigned either to attend
      (Study group) or not to attend (Control group) a rehabilitation residence for
      pregnant women with substance-use disorders. The primary objective was to measure
      differences in responses to a confidential 12-question survey addressing comfort
      levels and attitudes, at the beginning and end of the clerkship. RESULTS: Survey
      responses revealed improvements in students' comfort levels and attitudes toward
      pregnant women with substance-use disorders by attending the clinic alone or the
      clinic and residence. Those who attended the residence reported becoming more
      comfortable in talking with patients about adverse effects from substance abuse,
      more understanding of "street" terms, and stronger belief that patients will
      disclose their substance use to providers. Residents expressed more openly their
      hardships and barriers while trying to set therapeutic goals. CONCLUSIONS:
      Medical students became more comfortable and insightful about pregnant women with
      substance-use disorders after attending a rehabilitation residence in addition to
      a prenatal clinic dedicated to this population.

PMID- 23154693
TI  - Improving child and adolescent psychiatry education for medical students: an
      inter-organizational collaborative action plan.
AB  - OBJECTIVE: A new Child and Adolescent Psychiatry in Medical Education (CAPME)
      Task Force, sponsored by the Association for Directors of Medical Student
      Education in Psychiatry (ADMSEP), has created an inter-organizational partnership
      between child and adolescent psychiatry (CAP) educators and medical student
      educators in psychiatry. This paper outlines the task force design and strategic
      plan to address the long-standing dearth of CAP training for medical students.
      METHOD: The CAPME ADMSEP Task Force, formed in 2010, identified common challenges
      to teaching CAP among ADMSEP's CAPME Task Force members, utilizing focus-group
      discussions and a needs-assessment survey. The Task Force was organized into five
      major sections, with inter-organizational action plans to address identified
      areas of need, such as portable modules and development of benchmark CAP
      competencies. RESULTS/CONCLUSION: The authors predict that all new physicians,
      regardless of specialty, will be better trained in CAP. Increased exposure may
      also improve recruitment into this underserved area.

PMID- 23154694
TI  - Teaching to improve parent-child interaction: an educational case study.

PMID- 23154695
TI  - Teaching patient-centered care and systems-based practice in child and adolescent
      psychiatry.

PMID- 23154697
TI  - A four factor model of systems-based practices in psychiatry.

PMID- 23154699
TI  - A biopsychosocial approach to HIV/AIDS education for psychiatry residents.

PMID- 23154700
TI  - Primary treatment approaches in child and adolescent psychiatry training.

PMID- 23154702
TI  - The self-directed, structured summary as a teaching tool in a psychiatry journal
      club.

PMID- 23154703
TI  - Do I know what I do not know? Self-evaluation of performance in student-run
      seminars by psychiatry trainees in India.

PMID- 23154704
TI  - Chronic pain: a psychiatrist's personal illness narrative.

PMID- 23154705
TI  - Doing data-driven research in training: the experience of two residents.

PMID- 23154706
TI  - Electronic evaluation forms and the rate of completion of residency evaluations.

PMID- 23154707
TI  - Assessing the need for a multi-modal curriculum in psychopharmacology education.

PMID- 23154708
TI  - Disease characteristics should be taken into account when comparing attitudes and
      levels of stigma toward psychiatric and medical conditions.

PMID- 23154710
TI  - Portrayal of psychiatric disorders: are simulated patients authentic?

PMID- 23154712
TI  - Asthma in pregnancy:  management strategies.
AB  - PURPOSE OF REVIEW: Asthma is one of the most prevalent chronic medical conditions
      to complicate pregnancy. With approximately one-third of women experiencing a
      worsening of control during the course of their pregnancy, identifying those at
      greatest risk has the potential to improve maternal and fetal outcomes for a
      large number of pregnancies. Similarly, active management strategies that
      prioritize asthma control in this vulnerable population can have a far-reaching
      impact. RECENT FINDINGS: Demographic characteristics and patient noncompliance
      place certain populations of pregnant women at increased risk of poor asthma
      control during pregnancy. In addition, undertreatment and disparities in care of
      acute exacerbations during pregnancy likely contribute. Targeted educational
      interventions and treatment algorithms using objective markers of disease
      activity have shown improved outcomes in asthma control. SUMMARY: Active
      management strategies which focus on identifying patient-specific risk factors,
      patient and provider education, and targeted treatment interventions can improve
      asthma care for women during pregnancy.

PMID- 23154713
TI  - A multicenter prospective observational study of triple therapy with rabeprazole,
      amoxicillin and metronidazole for Helicobacter pylori in Japan.
AB  - OBJECTIVE: Triple therapy with rabeprazole (RPZ), amoxicillin (AMPC) and
      metronidazole (MNZ) (RPZ+AMPC+MNZ therapy: RAM therapy) has been approved by the
      Japanese Ministry of Health, Labour and Welfare as a second-line therapy for
      Helicobacter pylori-positive gastric and duodenal ulcers in Japan. The present
      multicenter prospective observational study aimed to investigate the safety and
      efficacy of RAM therapy in clinical practice. METHODS: Patients with H. pylori
      positive gastric or duodenal ulcers (including ulcer scars) in whom first-line
      therapy was unsuccessful were administered 10 mg of RPZ, 750 mg of AMPC and 250
      mg of MNZ twice daily for seven days (total: 14 doses) based on an approved dose
      and regimen. Patient background factors, including complications, previous
      medical history, concomitant drugs, eradication results and adverse events were
      recorded by the investigator. RESULTS: The incidence of adverse drug reactions
      was 2.21% and the H. pylori eradication rate was 92.8%. Subgroup analyses
      performed to investigate the patient background factors affecting safety and
      efficacy revealed no factors that significantly affected the incidence of adverse
      drug reactions or the H. pylori eradication rate. CONCLUSION: Amid reports of
      decreased eradication rates with clarithromycin-based first-line therapy, the
      >90%H. pylori eradication rate achieved in the present study demonstrates the
      clinical efficacy of RAM therapy in subjects in whom first-line therapy is
      unsuccessful.

PMID- 23154714
TI  - Influence of glycemic variability on the HbA1c level in elderly male patients
      with type 2 diabetes.
AB  - OBJECTIVE: To investigate the influence of glycemic variability on the HbA1c
      level in elderly male patients with type 2 diabetes (T2DM). METHODS: The 24-h
      glucose profiles were obtained using a continuous glucose monitoring system in
      291 elderly male type 2 diabetic patients. The relationship between the glycemic
      variability and HbA1c level was assessed in these patients. RESULTS: The mean
      amplitude of glycemic excursions (MAGE) in patients with HbA1c >=7.0% was
      significantly higher than in patients with HbA1c <7.0% (4.33+/-1.67 vs. 3.48+/
      1.46 mmol/L, p<0.001). A simple (Pearson's) correlation analysis indicated that
      the MAGE was significantly correlated with the HbA1c (r=0.229, p<0.001). Compared
      with the lowest quartile, the highest quartile of the MAGE was associated with a
      significantly increased risk of having a HbA1c >=7.0% after multiple adjustments
      (p (for trend) <0.001). CONCLUSION: The glycemic variability had a significant
      influence on the HbA1c level in elderly male patients with T2DM. The present data
      suggests that patients with higher glycemic variability might have higher HbA1c
      levels.

PMID- 23154715
TI  - The impact of a negative history of smoking on survival in patients with non
      small cell lung cancer detected with clinic-based screening programs.
AB  - OBJECTIVE: The aim of this study was to determine the epidemiological
      characteristics of never-smoking patients with non-small cell lung cancer (NSCLC)
      detected with clinic-based screening programs, focusing on clinical risk factors
      and survival. METHODS: The medical records of NSCLC patients (n=285) diagnosed at
      Fujisawa City Hospital between April 2000 and December 2010 with lesions that
      were originally detected with clinic-based screening programs in Fujisawa City
      were reviewed to identify the clinicopathological variables and survival
      outcomes. RESULTS: Of the 285 NSCLC patients, 95 (33.3%) were never-smokers. A
      comparison between the never-smoking and ever-smoking patients revealed that the
      never-smokers included a significantly greater proportion of women and patients
      with adenocarcinoma (86.3% vs. 12.6%: p<0.001 or 94.7% vs. 55.8%: p<0.001,
      respectively). The overall survival rate of the never-smoking patients was
      significantly superior to that of the ever-smokers (p=0.004). In addition to
      smoking status, factors found to be significantly associated with the overall
      survival rate in univariate analyses were gender, stage, histology and first line
      treatment. A multivariate analysis revealed smoking status to be an independent
      prognostic factor in addition to stage and first line treatment. CONCLUSION: The
      differences in the clinicopathological factors and survival outcomes between
      never-smoking and ever-smoking patients with NSCLC detected with clinic-based
      screening programs suggest that persuading people to never start smoking is
      important.

PMID- 23154716
TI  - Postpartum migraines: a long-term prospective study.
AB  - OBJECTIVE: There are many reports regarding the course of migraines during
      pregnancy. However, the prevalence and characteristics of migraines during the
      postpartum period have not been adequately investigated. We prospectively
      investigated the patients suffering from migraines over a long postpartum period
      in an obstetrics department in Japan. METHODS: We investigated the course of
      migraines experienced during the postpartum period by patients in a postnatal
      ward. The patients were surveyed during the first postpartum week and 1, 3, 6 and
      12 months after delivery. The patients were provided a headache diary to assess
      medication use and migraine attack frequency, severity (the faces pain scale) and
      duration. RESULTS: The migraine remission rate was 63%, 83% and 85% during the
      first, second and third trimesters, respectively. No patient experienced a
      worsening of headaches during pregnancy. Headache recurrence during the first
      month after delivery was more frequent in the patients >30 years of age than in
      those <=30 years of age (p<0.05). The percentage of women experiencing recurrence
      at 1, 3, 6 and 12 months after delivery was 63%, 75%, 78% (n=60) and 87.5%
      (n=40), respectively. In breastfeeding patients, the rates were 50%, 65.8%, 71.1%
      and 91.7% and in bottle feeding patients, the rates were 86.4%, 90.9%, 95.5% and
      81.3%, respectively. CONCLUSION: We found that 85% of the patients with migraines
      experience remission during pregnancy and that more than 50% experience
      recurrence during the first month after delivery. Until six months after
      delivery, breastfeeding is associated with a lower recurrence rate than bottle
      feeding.

PMID- 23154717
TI  - A patient with gastric adenosquamous carcinoma with intraperitoneal free cancer
      cells who remained recurrence-free with postoperative S-1 chemotherapy.
AB  - The case of a patient with gastric adenosquamous carcinoma with positive cancer
      cells on intraperitoneal washing cytology (CY1) who achieved a long recurrence
      free survival is herein reported. A 74-year-old man was found to have
      adenosquamous carcinoma of the stomach. Partial gastrectomy was performed, and a
      pathological examination confirmed a diagnosis of adenosquamous carcinoma with
      invasion into the serosa and lymph node metastasis. S-1 monotherapy was
      administered because a cytologic examination revealed that the patient's
      peritoneal washings were positive for cancer cells. The patient remains alive
      with no recurrence two years and 10 months after undergoing surgery.
      Postoperative chemotherapy with S-1 monotherapy is effective for treating
      adenosquamous carcinoma of the stomach with CY1 and might contribute to long-term
      survival.

PMID- 23154718
TI  - Chronic diarrhea as the presenting complaint of systemic lupus erythematosus in a
      man.
AB  - Systemic lupus can involve any part of the gastrointestinal (GI) tract. Diarrhea
      generally results from complications arising from infection, drugs or
      pancreatitis. We herein report the case of a 40-year-old hypertensive man with a
      psychotic disorder in whom the evaluation of chronic diarrhea revealed a
      diagnosis of systemic lupus erythematosus (SLE), diffuse proliferative
      glomerulonephritis and protein-losing enteropathy that required treatment with
      both steroids and mycophenolate mofetil. Over the following year, the patient
      developed atrial fibrillation, miliary tuberculosis and generalized clonic tonic
      seizures. He is currently under regular follow-up care and receives
      antiepileptics, antihypertensives, diltiazem, amiodarone and warfarin.

PMID- 23154719
TI  - Ulcerative colitis associated with isolated unilateral hypoglossal nerve palsy.
AB  - We herein describe a rare case of ulcerative colitis associated with unilateral
      hypoglossal nerve palsy. A 64-year-old woman developed severe active ulcerative
      colitis and was treated with prednisolone. The dose of oral prednisolone was
      reduced to 7.5 mg/day, following which the patient noticed slight dysphagia and a
      speech disturbance. She was diagnosed with unilateral hypoglossal nerve palsy,
      which was thought to be caused by mononeuritis. She was treated with intravenous
      methylprednisolone at a dose of 500 mg/day, which improved the neuropathy. When
      the neuropathy occurred, the patient was in a mildly active stage of ulcerative
      colitis. We concluded that the mononeuritis observed in the present case was
      likely an extraintestinal manifestation of ulcerative colitis.

PMID- 23154720
TI  - Giant-cell myocarditis complicated by heparin-induced thrombocytopenia.
AB  - Giant-cell myocarditis is a fatal autoimmune disorder that is often associated
      with other autoimmune diseases. We herein describe a case of giant-cell
      myocarditis complicated by heparin-induced thrombocytopenia (HIT). A 71-year-old
      woman was admitted to our hospital due to palpitations and ptosis.
      Echocardiography revealed hypokinesis in the left basal ventricular walls. Heart
      failure gradually developed, and the condition was complicated by HIT. The
      patient died of cardiogenic and septic shock caused by agranulocytosis. An
      autopsy showed giant-cell myocarditis. When severe left ventricular dysfunction
      due to an unknown cause is complicated by HIT, potential diagnoses of giant-cell
      and other types of autoimmune myocarditis should thus be investigated.

PMID- 23154721
TI  - A puzzling case of phospho-soda-induced hypocalcemia in a patient with multiple
      endocrine neoplasia type 1-associated primary hyperparathyroidism.
AB  - Although rare, symptomatic hypocalcemia may develop after the administration of
      phospho-soda. We herein present the case of a patient with phospho-soda-induced
      hypocalcemia who was surprisingly diagnosed with multiple endocrine neoplasia
      type 1 (MEN1) caused by a heterozygous mutation in the MEN1 gene
      (c628_631delACAG), thus resulting in a frameshift mutation (210ThrfsX224). In
      addition to being the first report of phospho-soda-induced hypocalcemia in a
      patient with MEN1-associated primary hyperparathyroidism, our report highlights
      the complex nature of calcium balance in the human body and helps clinicians to
      appreciate how confounding factors might affect the presentation of endocrine
      disorders.

PMID- 23154722
TI  - Acquired hemophilia A associated with IgG4-related lung disease in a patient with
      autoimmune pancreatitis.
AB  - Immunoglobulin G4 (IgG4)-related lung diseases can occur in patients with
      autoimmune pancreatitis (AIP). However, the causal relationship between AIP and
      acquired hemophilia A (AH) is unknown. We herein report the first case of AH
      associated with IgG4-related lung disease that developed in a patient with AIP. A
      65-year-old asymptomatic man with a history of AIP and sclerosing cholangitis
      diagnosed at the age of 57 was admitted to our hospital due to an abnormal
      reticulonodular shadow on chest X-ray. An examination of lung biopsy specimens
      revealed IgG4-positive plasma cell infiltration in the interstitium. The serum
      IgG4 level was elevated. One year later, the patient developed a progressive
      severe hematoma in the left femoral muscle. On admission, laboratory examinations
      revealed severe anemia with a markedly prolonged activated partial prothrombin
      time, a decreased level of factor VIII (FVIII) activity, and the existence of
      anti-FVIII antibodies. These findings were consistent with a diagnosis of AH. No
      relapse has been observed over the past 25 months, during which time,
      corticosteroid therapy has been continuously administered.

PMID- 23154723
TI  - Organizing pneumonia complicated by cyst and pneumothorax formation.
AB  - We present a case of organizing pneumonia complicated by pneumothorax in
      association with cyst formation that developed during corticosteroid treatment.
      Although it has been reported that the check-valve mechanism is a plausible cause
      of cyst and pneumothorax formation in patients with organizing pneumonia, the
      details of the corresponding pathological changes that occur in air-trapping have
      not been elucidated. A pathological examination of lung specimens obtained with
      video-assisted thoracoscopic surgery suggested that granulation tissues plugging
      the bronchiole lumens might be a potential cause of the check-valve mechanism in
      this case. In this report, we also reviewed eight other cases of organizing
      pneumonia with pneumothorax or cyst formation.

PMID- 23154724
TI  - Fatal community-acquired primary Candida pneumonia in an alcoholic patient.
AB  - A 54-year-old alcoholic woman developed fulminant community-acquired pneumonia.
      Despite receiving intensive support measures, she died four days after admission.
      An autopsy revealed bronchopneumonia with clusters of pseudohyphae and yeast-like
      fungi, and Candida albicans was isolated from both tracheal aspiration specimens
      obtained on admission and the postmortem lungs. The absence of vessel invasion or
      any other organ involvement led to a diagnosis of primary Candida pneumonia
      secondary to aspiration, rather than pulmonary seeding from systemic infection.
      Candida species isolated from respiratory tract samples are usually regarded as
      originating from colonization; however, the possibility for true Candida
      pneumonia should be taken into account, even in the setting of community-acquired
      pneumonia.

PMID- 23154725
TI  - Eosinophilic lung disease complicated by Kimura's disease: a case report and
      literature review.
AB  - Kimura's disease (KD) or eosinophilic lymphogranuloma is a rare chronic
      inflammatory disorder of unknown etiology that occurs primarily in Asians. A 51
      year-old man diagnosed three years earlier with KD of a left neck nodule was
      admitted to our hospital with a productive cough and pulmonary infiltration.
      Bronchoscopy was performed, and a diagnosis of eosinophilic lung disease (ELD)
      was made. The patient's condition improved after receiving corticosteroid
      treatment. Complications such as nephrotic syndrome have been reported in
      patients with KD; however, ELD has not been previously described. To the best of
      our knowledge, this is the first report of ELD related to KD.

PMID- 23154726
TI  - Divergence paralysis caused by acute midbrain infarction.
AB  - A 41-year-old woman with idiopathic thrombocytopenic purpura and dyslipidemia
      abruptly developed vertigo, truncal ataxia and divergence paralysis. Cranial
      magnetic resonance imaging demonstrated the presence of infarction in the left
      superior paramedian mesencephalic artery involving the vicinity of the
      periaqueductal gray matter. The symptoms rapidly resolved under the
      administration of anti-platelet agents. The precise location of the hypothetical
      divergence center of the ocular motor system remains unclear because the lesions
      responsible for divergence paralysis are rarely identified on neuroimaging. We
      emphasize that this is a first reported case of DP caused by acute midbrain
      infarction and speculate that the mesencephalic reticular formation may be
      partially involved.

PMID- 23154727
TI  - Recurrent anterior uveitis with hypopyon revealing relapsing polychondritis.
AB  - Relapsing polychondritis (RP) is a rare disease involving cartilaginous
      structures, predominantly the ears, nose and laryngotracheobronchial tree. The
      eyes, cardiovascular system, peripheral joints, skin, and central nervous system
      may also be affected. Involvement of all ocular structures has been described.
      Non-granulomatous uveitis is a common feature; however hypopyon is uncommon. We
      herein present the case of a 42-year-old man who had been diagnosed with
      bronchial asthma for a long period; and who presented with recurrent hypopyon
      uveitis as a revealing manifestation of relapsing polychondritis. We emphasize
      that RP should therefore be considered in the differential diagnosis of sterile
      hypopyon uveitis.

PMID- 23154728
TI  - ANCA-associated vasculitis with central retinal artery occlusion developing
      during treatment with methimazole.
AB  - A 63-year-old woman suddenly developed central retinal artery occlusion following
      a slight fever while being treated with methimazole (MMI) for hyperthyroidism.
      She was diagnosed to have anti-neutrophil cytoplasmic antibody (ANCA)-associated
      vasculitis (AAV) based on increased inflammatory reactions with positive
      myeloperoxidase-ANCA in the serum. Her visual acuity remained low despite
      immediate treatment with corticosteroids and cyclophosphamide after cessation of
      MMI, which may have played a role in the pathogenesis of AAV. Central retinal
      artery occlusion is a rare manifestation of AAV; however, it is important with
      regard to the possibility of serious sequelae.

PMID- 23154729
TI  - Foot ulcers caused by rheumatoid vasculitis in a patient with rheumatoid
      arthritis undergoing etanercept treatment.
AB  - A 59-year-old woman with a 10-year history of rheumatoid arthritis (RA) presented
      with chronic ulcers on both feet while undergoing treatment with etanercept.
      Rheumatoid vasculitis (RV) was diagnosed, and the patient was treated with
      immunosuppressant drugs and skin grafting. Although anti-tumor necrosis factor
      (TNF) agents are known to induce vasculitis, vasculitis can also be caused by
      active RA. Accordingly, the cause of vasculitis in RA patients receiving anti-TNF
      therapy must be evaluated carefully.

PMID- 23154730
TI  - Recurrent Helicobacter cinaedi cellulitis and bacteremia in a patient with
      systemic lupus erythematosus.
AB  - A 31-year-old woman who had developed systemic lupus erythematosus at 17 years of
      age was admitted to the hospital for suspected cellulitis in the lower
      extremities. A blood culture performed upon admission to the hospital detected
      Helicobacter cinaedi (H. cinaedi), which was also isolated in blood and fecal
      cultures obtained on the 42nd hospital day. Bacterial translocation of H. cinaedi
      present in the intestines may have led to the development of recurrent bacteremia
      and cellulitis. In cases such as this, appropriate antibiotics therapy might be
      needed for more than one month. Moreover, H. cinaedi, a cause of emerging
      infections, requires a long period of time to grow; therefore it is important to
      extend the culture duration when the presence of this bacterium is suspected.

PMID- 23154732
TI  - Raoultella ornithinolytica bacteremia in cancer patients: report of three cases.
AB  - Raoultella ornithinolytica is a Gram-negative aerobic bacillus reclassified in
      the new genus from the Klebsiella species based on new genetic approaches;
      however, human infections caused by R. ornithinolytica are rare. We herein report
      three cases of R. ornithinolytica bacteremia associated with biliary tract
      infections in cancer patients. R. ornithinolytica can be a causative pathogen of
      biliary tract infection in cancer patients.

PMID- 23154731
TI  - Spondylodiscitis complicated by an epidural abscess and meningitis caused by
      Bacteroides fragilis.
AB  - Bacteroides fragilis is a rare causative agent of spondylodiscitis. The
      pathophysiology of B. fragilis in spondylodiscitis remains largely unclear
      because of its rare occurrence. We herein report a case of spondylodiscitis
      complicated by an epidural abscess and meningitis; B. fragilis was detected in
      the blood of the patient. Moreover, the patient had a splenic abscess that was
      confirmed on magnetic resonance imaging. The patient completely recovered with
      antimicrobial therapy alone.

PMID- 23154733
TI  - Sudden cardiac arrest caused by tuberculous pericarditis with hemorrhagic
      pericardial effusion.
AB  - As tuberculosis still exists in Japan, tuberculous pericarditis is a major health
      issue. Tuberculous pericarditis is difficult to diagnose and leads to poor
      outcomes when left untreated. We herein report the case of a patient who was
      admitted to the hospital after undergoing resuscitation for cardiopulmonary
      arrest. Mycobacterium tuberculosis was detected in his hemorrhagic pericardial
      fluid and tuberculous pericarditis was diagnosed. The administration of
      antituberculous medication resulted in marked improvements. A diagnosis of
      tuberculous pericarditis, in addition to other causes such as malignant tumors,
      should therefore be considered in the differential diagnosis for cases presenting
      with hemorrhagic pericardial effusion, even in those involving sudden cardiac
      arrest.

PMID- 23154734
TI  - Tuberculous cellulitis in a patient with chronic kidney disease and polymyalgia
      rheumatica.
AB  - An 89-year-old man with advanced renal failure, polymyalgia rheumatica and a past
      history of tuberculosis was admitted with a high fever. Erythema and swelling
      appeared in the femoral region. Since the cellulitis failed to respond to
      antibiotic therapy, a skin biopsy was performed. The specimen showed the presence
      of epithelioid cell granuloma and panniculitis. Acid-fast organisms were found on
      Ziehl-Neelsen staining. A polymerase chain reaction test of tuberculosis was
      positive. Although a diagnosis of miliary tuberculosis was suggested,
      examinations of a bone marrow biopsy and fundoscopy revealed normal results. The
      patient's symptoms improved following treatment with isoniazid, rifampicin and
      ethambutol. This case represents an unusual presentation of tuberculous
      cellulitis in an immunocompromised patient.

PMID- 23154735
TI  - Severe Legionnaires' disease with pneumonia and biopsy-confirmed myocarditis most
      likely caused by Legionella pneumophila serogroup 6.
AB  - We herein describe the successful treatment of a patient with possible Legionella
      pneumophila serogroup 6 infection complicated by pneumonia and myocarditis. A 32
      year-old man presented with a five-day history of cough, dyspnea and chest pain.
      Chest radiography revealed patchy opacities in both lungs suggestive of bilateral
      pneumonia, and a urinary antigen test for Legionella pneumophila was positive.
      After admission, the patient developed congestive heart failure due to
      pathologically confirmed myocarditis. He was successfully treated with
      minocycline, macrolide, steroids and noninvasive positive-pressure ventilation
      (NPPV). He eventually recovered with a normalized cardiac function. L.
      pneumophila serogroup 6 was isolated from the bathwater in the patient's home.

PMID- 23154736
TI  - Elevated coagulation factor VIII plasma activity in a patient with
      lymphangiosarcoma.
AB  - A 72-year-old woman was referred to our hospital for palliative care. Fifteen
      years earlier, she had undergone total hysterectomy and radiotherapy for cervical
      cancer. One year before her referral, she visited a hospital due to a gait
      disturbance and was diagnosed with lymphangiosarcoma. The level of coagulation
      factor VIII plasma activity was >201% (normal range: 62-145%) and the
      immunohistochemical results were positive for factor VIII-related antigen in a
      tumor specimen. To the best of our knowledge, this is the first report of high
      coagulation factor VIII plasma activity in a patient with lymphangiosarcoma.

PMID- 23154737
TI  - A giant amebic liver abscess.

PMID- 23154738
TI  - Polysplenia in an adult patient.

PMID- 23154739
TI  - Kawasaki disease with a giant coronary aneurysm.

PMID- 23154740
TI  - Massive thyroid hematoma developing after a fine-needle aspiration biopsy.

PMID- 23154741
TI  - Low bone mass in Ehlers-Danlos syndrome.

PMID- 23154742
TI  - Churg-Strauss syndrome with endobronchial eosinophilic vasculitis.

PMID- 23154743
TI  - Downgaze-limited diplopia caused by midbrain infarction.

PMID- 23154744
TI  - Chest wall tuberculosis.

PMID- 23154745
TI  - Green plasma and pregnancy.

PMID- 23154746
TI  - How much do focal infarcts distort white matter lesions and global cerebral
      atrophy measures?.
AB  - BACKGROUND: White matter lesions (WML) and brain atrophy are important biomarkers
      in stroke and dementia. Stroke lesions, either acute or old, symptomatic or
      silent, are common in older people. Such stroke lesions can have similar signals
      to WML and cerebrospinal fluid (CSF) on magnetic resonance (MR) images, and may
      be classified accidentally as WML or CSF by MR image processing algorithms,
      distorting WML and brain atrophy volume from the true volume. We evaluated the
      effect that acute or old stroke lesions at baseline, and new stroke lesions
      occurring during follow-up, could have on measurement of WML volume, cerebral
      atrophy and their longitudinal progression. METHODS: We used MR imaging data from
      patients who had originally presented with acute lacunar or minor cortical
      ischaemic stroke symptoms, recruited prospectively, who were scanned at baseline
      and about 3 years later. We measured WML and CSF volumes (ml) semi-automatically.
      We manually outlined the acute index stroke lesion (ISL), any old stroke lesions
      present at baseline, and new lesions appearing de novo during follow-up. We
      compared baseline and follow-up WML volume, cerebral atrophy and their
      longitudinal progression excluding and including the acute ISL, old and de novo
      stroke lesions. A non-parametric test (Wilcoxon's signed rank test) was used to
      compare the effects. RESULTS: Among 46 patients (mean age 72 years), 33 had an
      ISL visible on MR imaging (median volume 2.05 ml, IQR 0.88-8.88) and 7 of the 33
      had old lacunes at baseline: WML volume was 8.54 ml (IQR 5.86-15.80) excluding
      versus 10.98 ml (IQR 6.91-24.86) including ISL (p < 0.001). At follow-up, median
      39 months later (IQR 30-45), 3 patients had a de novo stroke lesion; total stroke
      lesion volume had decreased in 11 and increased in 22 patients: WML volume was
      12.17 ml (IQR 8.54-19.86) excluding versus 14.79 ml (IQR 10.02-38.03) including
      total stroke lesions (p < 0.001). Including/excluding lacunes at baseline or
      follow-up also made small differences. Twenty-two of the 33 patients had tissue
      loss due to stroke lesions between baseline and follow-up, resulting in a net
      median brain tissue volume loss (i.e. atrophy) during follow-up of 24.49 ml (IQR
      12.87-54.01) excluding versus 24.61 ml (IQR 15.54-54.04) including tissue loss
      due to stroke lesions (p < 0.001). Including stroke lesions in the WML volume
      added substantial noise, reduced statistical power, and thus increased sample
      size estimated for a clinical trial. CONCLUSIONS: Failure to exclude even small
      stroke lesions distorts WML volume, cerebral atrophy and their longitudinal
      progression measurements. This has important implications for design and sample
      size calculations for observational studies and randomised trials using WML
      volume, WML progression or brain atrophy as outcome measures. Improved methods of
      discriminating between stroke lesions and WML, and between tissue loss due to
      stroke lesions and true brain atrophy are required.

PMID- 23154749
TI  - Computational Hammett analysis of redox based oxy-insertion by Pt(II) complexes.
AB  - A computational Hammett analysis of oxy-insertion into platinum-aryl bonds is
      performed. Modeled transformations involve the two-step conversion of
      [((X)bpy)Pt(R)(OY)](+) (R = p- or m-X-C(6)H(4); Y = 4- or 3-X-pyridine; (X)bpy =
      4,4'- or 5,5'-X-bpy; X = NO(2), H, OMe, NMe(2)) proceeding through a Pt-oxo
      intermediate to form aryloxide [((X)bpy)Pt(OR)(Y)](+), which contrasts a one-step
      non-redox (Baeyer-Villiger) oxy-insertion. A structural connection is proposed
      between redox and non-redox transition states, linked to, among other parameters,
      oxidant identity. The electronic impact of the catalytic components is compared
      to previous Hammett studies on OMBV transformations. The Hammett sensitivity for
      aryl migration is diminished for the migrating group (R) and leaving group (Y),
      components as compared to OMBV transitions, while the bipyridine supporting
      ligand (L(n)) has an increased impact. The Hammett impact of R, Y and L(n) upon
      the aryl migration transition state is small in a global sense, ca. 5 kcal mol(
      1); therefore, we conclude that the metal and oxidant are the most important
      factors in controlling oxy-insertion kinetics for these late metal systems. These
      results also point to a possible mechanistic advantage for redox over non-redox
      functionalization of hydrocarbons to alcohols.

PMID- 23154748
TI  - Aggressive B-cell lymphomas: how many categories do we need?
AB  - Aggressive B-cell lymphomas are diverse group of neoplasms that arise at
      different stages of B-cell development and by various mechanisms of neoplastic
      transformation. The aggressive B-cell lymphomas include many types, subtypes and
      variants of diffuse large B-cell lymphoma (DLBCL), Burkitt lymphoma (BL), mantle
      cell lymphoma and its blastoid variant, and B lymphoblastic lymphoma. Differences
      in histology, cytogenetic and molecular abnormalities, as well as the
      relationship with the tumor microenvironment, help define characteristic
      signatures for these neoplasms, and in turn dictate potential therapeutic
      targets. Rather than survey the entire spectrum of aggressive B-cell lymphomas,
      this report aims to identify and characterize important clinically aggressive
      subtypes of DLBCL, and explore the relationship of DLBCL to BL and the gray zone
      between them (B-cell lymphoma unclassifiable with features intermediate between
      DLBCL and BL).

PMID- 23154750
TI  - Investigating the robustness of ion beam therapy treatment plans to uncertainties
      in biological treatment parameters.
AB  - Uncertainties in determining clinically used relative biological effectiveness
      (RBE) values for ion beam therapy carry the risk of absolute and relative
      misestimations of RBE-weighted doses for clinical scenarios. This study assesses
      the consequences of hypothetical misestimations of input parameters to the RBE
      modelling for carbon ion treatment plans by a variational approach. The impact of
      the variations on resulting cell survival and RBE values is evaluated as a
      function of the remaining ion range. In addition, the sensitivity to
      misestimations in RBE modelling is compared for single fields and two opposed
      fields using differing optimization criteria. It is demonstrated for single
      treatment fields that moderate variations (up to +/-50%) of representative
      nominal input parameters for four tumours result mainly in a misestimation of the
      RBE-weighted dose in the planning target volume (PTV) by a constant factor and
      only smaller RBE-weighted dose gradients. Ensuring a more uniform radiation
      quality in the PTV eases the clinical importance of uncertainties in the
      radiobiological treatment parameters, as for such a condition uncertainties tend
      to result only in a systematic misestimation of RBE-weighted dose in the PTV by a
      constant factor. Two opposed carbon ion fields with a constant RBE in the PTV are
      found to result in rather robust conditions. Treatments using two ion species may
      be used to achieve a constant RBE in the PTV irrespective of the size and depth
      of the spread-out Bragg peak.

PMID- 23154751
TI  - Variation of tibial plateau geometry and cruciate ligament coordinates in six
      breeds of dogs.
AB  - OBJECTIVES: The first aim of this study was to examine whether or not variations
      concerning the conformational characteristics of the proximal surface of the
      tibial plateau exist among six different dog breeds as well as within the same
      breed. The second aim of this study was to determine the coordinates of the
      cruciate ligaments. METHODS: One hundred and four tibias of 52 mature dogs from
      six different breeds were used. Photographs of the proximal surface of tibial
      plateau were taken, and measurements for the length, width and area of the tibial
      plateau, and the lateral and medial condyles were taken. In addition, the
      intercondylar width, height of Gerdy's tubercle, popliteal notch depth, and
      extensor groove depth were measured and recorded. The quotients from these
      measurements were calculated and compared amongst the dog breeds. The coordinates
      of the cruciate ligaments, according to the centre of tibial plateau, were also
      determined. RESULTS: Based on the calculated quotients, variations in the
      geometry of the tibial plateau geometry were common among the breeds. Within the
      same breed, on the other hand, length and width measurements of the tibial
      plateau were the least variable parameters among the other parameters examined.
      The cranial cruciate ligament was located in front of the surface centre of
      tibial plateau in all breeds. The position of cranial cruciate ligament was more
      variable in the craniocaudal direction than that observed in the mediolateral
      direction; this was the exact opposite of caudal cruciate ligament. CLINICAL
      SIGNIFICANCE: The inter-breed variations of the quotients determined in the
      present study may facilitate attempts aimed to assess the risk factors of stifle
      joint injury and to design total knee prostheses.

PMID- 23154752
TI  - Fluorescence enhancement from nano-gap embedded plasmonic gratings by a novel
      fabrication technique with HD-DVD.
AB  - We demonstrate strong electromagnetic field enhancement from nano-gaps embedded
      in silver gratings for visible wavelengths. These structures fabricated using a
      store-bought HD-DVD worth $10 and conventional micro-contact printing techniques
      have shown maximum fluorescence enhancement factors of up to 118 times when
      compared to a glass substrate under epi-fluorescent conditions. The novel
      fabrication procedure provides for the development of a cost-effective and facile
      plasmonic substrate for low-level chemical and biological detection.
      Electromagnetic field simulations were also performed that reveal the strong
      field confinement in the nano-gap region embedded in the silver grating, which is
      attributed to the combined effect of localized as well as propagating surface
      plasmons.

PMID- 23154753
TI  - Plaque characteristics of asymptomatic carotid stenosis and risk of stroke.
AB  - BACKGROUND: The optimal treatment of asymptomatic carotid stenosis (ACS) is
      controversial. To optimize the risk-benefit ratio of carotid artery
      revascularization, it is crucial to identify ACS patients who are at increased
      stroke risk. Recent data suggest that plaque vulnerability depends on its
      composition. Therefore, we assessed plaque composition in ACS to determine
      predictors for ipsilateral cerebrovascular events. METHODS: 62 patients with 65
      ACS >=50% underwent 3-T MRI of the carotid bifurcation (TOF, special dark-blood
      weighted noncontrast and contrast-enhanced T(1) and T(2) images) and of the
      brain. The different plaque components (lipid core, intraplaque hemorrhage,
      calcification and the status of the fibrous cap) were assessed. Furthermore, the
      plaque volume and the volume of clinically silent cortical and subcortical
      infarcts in the territory of the stenosed carotid artery as seen on FLAIR images
      were determined by using a semi-automated software. Carotid stenosis was
      considered asymptomatic if there had not been any clinically apparent ischemic
      events in the corresponding vascular territory within the previous 6 months.
      During follow-up, information on the occurrence of cerebrovascular events,
      medical treatment and sonographic changes of the stenosis was collected. RESULTS:
      At baseline, 24 ACS (37%) were classified as high grade. A lipid-rich necrotic
      core was the dominant plaque component in 16 ACS (25%). The plaque volume was
      higher in ACS with a lipid-rich necrotic core as dominant plaque component (p =
      0.002) and in patients with prior stroke/TIA (p = 0.010). After a median follow
      up of 18.9 months (interquartile range 3.5-30.1) there were 2 ipsilateral strokes
      and 3 ipsilateral TIAs. The average annual event rate was 7.7%. A lipid-rich
      necrotic core (HR 7.21; 95% CI 1.12-46.28; p = 0.037), sonographic progression of
      the stenosis (HR 7.00; 95% CI 1.13-41.34; p = 0.036), history of stroke (HR
      11.03; 95% CI 1.23-99.36; p = 0.032), and the volume of clinically asymptomatic
      ischemic brain lesions (HR 1.14/cm(3); 95% CI 1.03-1.25; p = 0.008) predicted
      cerebrovascular events. Patients on statin therapy at follow-up were at lower
      risk of events (HR 0.17; 95% CI 0.03-1.00; p = 0.05). CONCLUSIONS: In addition to
      medical history and sonographic findings, a lipid-rich necrotic core within the
      plaque turned out as a predictor of cerebrovascular events. Therefore, MR imaging
      of carotid plaques deserves further attention and might be helpful to improve
      risk stratification of asymptomatic carotid disease. The identified predictors
      could be combined in a risk model and tested in larger prospective studies.

PMID- 23154754
TI  - Two thermoformable spiral metallic ureteral stents in a patient with ileal
      conduit and distal stenosis of the ureters.
AB  - The insertion of two thermoformable ureteral titanium spiral stents (Memokath(r)
      051) through ileal conduit due to bilateral ureteral stenosis distally has not
      been described in the English literature so far. We present the case of a young
      female patient with a history of ileal conduit urinary diversion due to
      congenital urinary bladder exstrophy, who had multiple previous surgeries and the
      insertion of two Memokath(r) ureteral stents in both ureters due to distal
      ureteral stenosis.

PMID- 23154755
TI  - An international survey of deep brain stimulation procedural steps.
AB  - BACKGROUND: Deep brain stimulation (DBS) surgery is standard of care for the
      treatment of certain movement disorders. OBJECTIVE: We sought to characterize the
      spectrum of steps performed in DBS surgery, at centers around the world where
      this surgery is performed. METHODS: We identified the main steps in DBS surgery
      workflow and grouped these 19 steps into 3 phases (preoperative, operative, and
      postoperative). A survey tool, informed by a pilot survey, was administered
      internationally by trained study personnel at high- and low-volume DBS centers.
      Procedural components, duration, and surgeon motivational factors were assessed.
      Cluster analysis was used to identify procedural and behavioral clusters.
      RESULTS: One hundred eighty-five procedure workflow surveys (143 DBS centers) and
      65 online surveys of surgeon motivational drivers were completed (45% response
      rate). Significant heterogeneity in technique, operative time, and surgeon
      motivational drivers was reported across centers. CONCLUSIONS: We provide a
      description of the procedural steps involved in DBS surgery and the duration of
      these steps, based on an international survey. These data will enable individual
      surgeons and centers to examine their own experience relative to colleagues at
      other centers and in other countries. Such information could also be useful in
      comparing efficiencies and identifying workflow obstacles between different
      hospital environments.

PMID- 23154756
TI  - Increased arterial stiffness and extracellular matrix reorganization in
      intrauterine growth-restricted fetal sheep.
AB  - BACKGROUND: Fetal intrauterine growth restriction (IUGR) results in increased
      placental resistance to blood flow, fetal hypertension, and increased pulsatility
      stresses shown to lead to vascular remodeling. We tested our hypothesis that IUGR
      causes decreased compliance in the carotid and umbilical arteries due to altered
      extracellular matrix (ECM) composition and structure. METHODS: A sheep model of
      placental insufficiency-induced IUGR (PI-IUGR) was created by exposure of the
      pregnant ewe to elevated ambient temperatures. Umbilical and carotid arteries
      from near-term fetuses were tested with pressure-diameter measurements to compare
      passive compliance in control and PI-IUGR tissues. ECM composition was measured
      via biochemical assay, and the organization was determined by using histology and
      second-harmonic generation imaging. RESULTS: We found that PI-IUGR increased
      arterial stiffness with increased collagen engagement, or transition stretch. PI
      IUGR carotid arteries exhibited increased collagen and elastin quantity, and PI
      IUGR umbilical arteries exhibited increased sulfated glycosaminoglycans.
      Histomorphology showed altered collagen-to-elastin ratios with altered cellular
      proliferation. Increased stiffness indicates altered collagen-to-elastin ratios
      with less elastin contribution leading to increased collagen engagement.
      CONCLUSION: Because vessel stiffness is a significant predictor in the
      development of hypertension, disrupted ECM deposition in IUGR provides a
      potential link between IUGR and adult hypertension.

PMID- 23154757
TI  - Noninvasive measurement of intestinal epithelial damage at time of refeeding can
      predict clinical outcome after necrotizing enterocolitis.
AB  - BACKGROUND: Reintroduction of enteral nutrition in neonates with necrotizing
      enterocolitis (NEC) should take place when the gut is ready for its normal
      function. Too early a start of oral feeding might lead to disease relapse,
      whereas prolonged discontinuation of enteral nutrition is associated with
      impaired gut function and parenteral nutrition-related complications. This study
      evaluated whether noninvasive urinary measurement of intestinal fatty acid
      binding protein (I-FABP) at the time of refeeding can predict clinical outcome in
      neonates with NEC. METHODS: Urinary I-FABP concentrations were measured in 21
      infants with NEC just before reintroducing enteral nutrition. Poor outcome was
      defined as unsuccessful reintroduction of enteral feeding (EF), (re)operation for
      NEC, or death related to NEC after reintroduction of EF. RESULTS: Median urinary
      I-FABP levels in neonates with poor outcome (n = 5) were significantly higher as
      compared with I-FABP levels in neonates with good outcome (n = 16) (P < 0.01). A
      clinically significant cutoff value of 963 pg/ml was found to discriminate
      between infants with poor outcome and those with good outcome (sensitivity 80%,
      specificity 94%). CONCLUSION: Noninvasive urinary I-FABP measurement at time of
      refeeding differentiates neonates with poor outcome from neonates with good
      outcome in NEC. Urinary I-FABP measurement may therefore be helpful in the timing
      of EF in neonates with NEC.

PMID- 23154758
TI  - Development of methods to distinguish between durum/common wheat and common wheat
      in blended flour using PCR.
AB  - A PCR-based method was developed to distinguish between durum/common wheat and
      common wheat by leveraging slight differences of DNA sequence in Starch Synthase
      II (SS II) coded on wheat A, B and D genomes. A primer pair, SS II ex7-U/L, was
      designed to hybridize with a conserved DNA sequence region found in SS II-A, B
      and D genes. Another primer pair, SS II-D 1769U/1889L, was constructed to
      recognize a unique sequence in the SS II-D gene. The target region of SS II ex7
      U/L with the size of 114 bp was amplified from durum and common wheat DNA, while
      no amplification was observed from any cereals other than those in the wheat
      genus. A DNA fragment with the size of 121 bp was specifically amplified from
      common wheat with SS II-D 1769U/1889L. In blended flour prepared from wheat and
      other cereals, the developed PCR system composed of two primer pairs effectively
      detected durum/common wheat and common wheat. These results suggested that PCR
      using two primer pairs is useful for detecting common and/or durum wheat in
      blended flour and could be utilized to ensure accurate food labeling.

PMID- 23154759
TI  - An endogenous reference gene of common and durum wheat for detection of
      genetically modified wheat.
AB  - To develop a method for detecting GM wheat that may be marketed in the near
      future, we evaluated the proline-rich protein (PRP) gene as an endogenous
      reference gene of common wheat (Triticum aestivum L.) and durum wheat (Triticum
      durum L.). Real-time PCR analysis showed that only DNA of wheat was amplified and
      no amplification product was observed for phylogenetically related cereals,
      indicating that the PRP detection system is specific to wheat. The intensities of
      the amplification products and Ct values among all wheat samples used in this
      study were very similar, with no nonspecific or additional amplification,
      indicating that the PRP detection system has high sequence stability. The limit
      of detection was estimated at 5 haploid genome copies. The PRP region was
      demonstrated to be present as a single or double copy in the common wheat haploid
      genome. Furthermore, the PRP detection system showed a highly linear relationship
      between Ct values and the amount of plasmid DNA, indicating that an appropriate
      calibration curve could be constructed for quantitative detection of GM wheat.
      All these results indicate that the PRP gene is a suitable endogenous reference
      gene for PCR-based detection of GM wheat.

PMID- 23154760
TI  - Aflatoxins B and g contamination and aflatoxigenic fungi in nutmeg.
AB  - This study examined the distribution of aflatoxigenic fungi in 25 imported
      Indonesian nutmeg samples contaminated with aflatoxins Bs or Bs and Gs. The
      incidence of aflatoxigenic fungi in the samples contaminated with high levels of
      aflatoxin was significantly higher than that in the samples with low levels of
      the toxins(r=0.752). The aflatoxin production of isolates from the samples in
      cultures of YES broth was examined by means of TLC and HPLC analyses. The ability
      of isolates to produce aflatoxins did not necessarily correlate with the
      contamination levels of aflatoxin in the samples. We isolated aflatoxins B and G
      producing fungi from 3 samples contaminated with the high levels of aflatoxins B
      and G. The aflatoxigenic isolates were identified as Aspergillus nomius and A.
      bombycis based on morphological characters, growth rates at 37 degrees C and 42
      degrees C and also molecular-genetic methods. Our results indicate that these two
      species are mainly responsible for aflatoxin G contamination in nutmeg products.

PMID- 23154761
TI  - Determination method of clomeprop and clomeprop acid in livestock and seafood
      products by LC-MS/MS.
AB  - A method using liquid chromatography with tandem mass spectrometry has been
      developed for the determination of clomeprop and its metabolite clomeprop acid in
      livestock and seafood products. Clomeprop and clomeprop acid were extracted with
      acetone-n-hexane mixture under acidic conditions, and were defatted by liquid
      liquid separation using acetonitrile and n-hexane, followed cleanup with SAX and
      PSA cartridges. The average recoveries from 10 kinds of food (bovine muscle,
      bovine fat, bovine liver, milk, yellowtail, salmon, eel, fresh water clam, egg
      and honey) spiked at the level of the MRLs or at uniform limits (0.01 ppm) were
      in the range of 81-97% for clomeprop and 93-101% for clomeprop acid.
      Repeatability was in the range of 2.1-14% for clomeprop and 1.3-4.0% for
      clomeprop acid. The quantitation limits were 0.002 mg/kg for clomeprop and
      0.00154 mg/kg (0.002 mg/kg as clomeprop) for clomeprop acid.

PMID- 23154762
TI  - Investigation of whether CLSI broth microdilution method is applicable for MICs
      Determination of Enterococcus species.
AB  - The broth microdilution (BMD) method is an antimicrobial susceptibility testing
      method defined as a guideline by the Clinical and Laboratory Standards Institute
      (CLSI). To date, the Japanese Veterinary Antimicrobial Resistance Monitoring
      System (JVARM), has adopted the agar dilution (AD) method for monitoring
      antimicrobial resistances targeting isolates of Enterococcus spp., found in the
      fecal flora of food-producing animals, as indicator bacteria. However, the AD
      method is tedious, and time-consuming. In order to examine whether it could be
      replaced with the BMD method, the two methods were compared in terms of the
      correlation of MICs. In this study, the BMD results agreed with the AD results
      within +/-1 log(2) dilutions in 72.3% of cases, except for the antimicrobial feed
      additive, Nosiheptide (NHT). Similarly, except for NHT, the MIC(50) and MIC(90)
      values obtained by the two methods were well correlated. In conclusion, our
      results indicate that the BMD method might be suitable for antimicrobial
      susceptibility testing targeting Enterococcus spp..

PMID- 23154763
TI  - Behavior of pesticides in coffee beans during the roasting process.
AB  - In Japan, maximum residue limits for pesticides (MRL) in coffee are set on green
      coffee beans, but not roasted coffee beans, although roasted beans are actually
      used to prepare coffee for drinking. Little is known about the behavior of
      pesticides during the roasting process. In the present study, we examined the
      changes in the concentration of pesticide (organochlorine: gamma-BHC, chlordane
      and heptachlor) residues in coffee beans during the roasting process. We prepared
      green coffee beans spiked with these pesticides (0.2 and 1.0 MUg/g), and the
      residue levels in the beans were measured before and after the roasting process.
      We determined the residual rate after the roasting process. gamma-BHC was not
      detectable at all, and more than 90% of chlordane was lost after the roasting
      (3.1 and 5.1% of chlordane remained in the beans spiked with 0.2 and 1.0 MUg/g of
      chlordane, respectively). A low level of heptachlor (0.72%) was left in the
      coffee beans spiked with 1 MUg/g of heptachlor. Disappearance of gamma-BHC during
      the roasting process may be due to the high vapor pressure of gamma-BHC, while
      chlordane has a lower vapor pressure. We also examined the behavior of piperonyl
      butoxide and atrazine during the roasting process. Piperonyl butoxide behaved
      similarly to chlordane, but atrazine disappeared after the roasting process,
      because it is unstable to heat.

PMID- 23154764
TI  - Discrimination of mushrooms causing food-poisoning incidents by using DNA
      sequence analysis.
AB  - In this study, the identification of mushrooms by using DNA analysis was
      investigated. Our analysis of internal transcribed spacer (ITS) regions revealed
      that a DNA-based method could be applicable for samples that are difficult to
      distinguish in terms of the morphological characteristics. PCR amplification
      using templates extracted from cooked samples gave sufficient fragments to
      analyze the sequence. However, treatment with simulated gastric fluid (SGF) for
      more than 30 min affected the analysis of the ITS region. Application to samples
      of vomit is also discussed.

PMID- 23154766
TI  - Ki67 labeling index in neuroendocrine tumors of the gastrointestinal and
      pancreatobiliary tract: to count or not to count is not the question, but rather
      how to count.

PMID- 23154765
TI  - Development and validation of rapid analysis method for multi-class veterinary
      drugs in livestock products by LC-MS/MS.
AB  - A method for rapid analysis of multi-class residual veterinary drugs in livestock
      products was developed and validated in accordance with the Japanese guideline
      for pesticides. Using LC-MS/MS, 43 multi-class veterinary drugs, including
      sulfonamides, quinolones, coccidiostats and antiparasites, could be analyzed
      simultaneously in only 18 minutes. The extraction process was developed by
      modifying the QuEChERS approach to provide faster and less expensive extraction.
      The samples were extracted by using two kinds of solvent, acetonitrile and
      acetonitrile including 1 vol% formic acid, and salted out with magnesium sulfate,
      trisodium citrate and sodium chloride. Using these two extractants, 40 out of 43
      drugs satisfied the guideline criteria in bovine muscle and swine muscle, 39
      drugs were found in chicken muscle, and 37 drugs were found in eggs. The limit of
      quantification was less than the MRL for all analytes.

PMID- 23154767
TI  - Clinicopathologic analysis of matched primary and recurrent endometrial
      carcinoma.
AB  - It is unknown whether the type and grade of a primary endometrial carcinoma is
      reliably maintained in recurrence. All matched primary and recurrent endometrial
      carcinomas diagnosed from 2000 to 2010 at our institution were identified; 34
      cases had available slides. Histologic classification was performed using
      modifications to the World Health Organization criteria. Immunohistochemical
      analysis for p53, p16, progesterone receptor (PR), and DNA mismatch-repair
      proteins (MMR) (MLH1, MSH2, MSH6, and PMS2) was performed. Endometrioid carcinoma
      recurrences were mostly local, whereas serous carcinoma recurrences were mostly
      peritoneal. Compared with endometrioid carcinoma patients, serous carcinoma
      patients were older, presented at high stage, and had shorter survival. Serous
      carcinomas were the most common recurrent endometrial carcinoma (18/34 cases).
      Overall, 21 cases (62%) displayed similar morphology when comparing primary and
      recurrent carcinomas, whereas 13 displayed discordant morphology. Seven of 13
      endometrioid carcinomas (54%) had a morphologically discordant recurrence,
      compared with 3 of 14 serous carcinomas (21%), 1 of 4 morphologically ambiguous
      carcinomas (25%), and both mixed epithelial carcinomas. Serous and
      morphologically ambiguous carcinomas therefore demonstrated relative morphologic
      fidelity compared with endometrioid carcinomas. Four morphologically discordant
      cases demonstrated either pure clear cell carcinoma or clear cell features at
      recurrence. Seven of 23 matched pairs displayed discordant PR results, with 5
      cases, including both endometrioid and serous carcinomas, showing diminished PR
      expression at recurrence. p53, p16, and DNA MMR staining results were generally
      concordant when evaluating matched pairs, with only occasional exceptions. Sixty
      four percent of all pure endometrioid carcinomas and mixed epithelial carcinomas
      with an endometrioid component showed loss of expression of MLH1 and/or PMS2; no
      serous carcinoma demonstrated this abnormality. Clinical and immunohistochemical
      data supported the use of modifications to the World Health Organization
      diagnostic criteria. More importantly, the data suggest that when confronted with
      recurrent endometrial carcinoma, particularly a serous carcinoma, it is
      reasonable to base therapeutic decisions on the type of the primary tumor,
      especially if sampling or excising the recurrent tumor is problematic. However,
      in light of the PR results, sampling a recurrent endometrioid carcinoma may be
      worthwhile if hormonal therapy is planned. Recurrent endometrioid carcinoma may
      be enriched for tumors with DNA MMR abnormalities.

PMID- 23154768
TI  - Silver-enhanced in situ hybridization for determination of EGFR copy number
      alterations in non-small cell lung cancer.
AB  - Epidermal growth factor receptor (EGFR) gene mutation and high gene copy number
      (CN) predict response to EGFR tyrosine kinase inhibitor therapy in the
      adenocarcinoma subtype of non-small cell lung cancer (NSCLC). The aims of this
      study were first to compare automated enzyme metallographic silver-enhanced in
      situ hybridization (SISH) with conventionally used fluorescence in situ
      hybridization (FISH) in the determination of EGFR CN in NSCLC tissue sections,
      and second to assess the association of EGFR CN with EGFR mutations and
      clinicopathological parameters. FISH and SISH were performed on tissue
      microarrays and large sections. Samples from 56 consecutively surgically resected
      NSCLC patients (cohort 1) and from 60 selected lung adenocarcinoma patients
      (cohort 2) were analyzed. EGFR CN was classified applying the Colorado criteria,
      and agreement between both methods was evaluated using kappa values. EGFR CN was
      compared with EGFR protein expression and EGFR gene mutations. The results of
      SISH and FISH were identical in 114 of the 116 cases examined using the 2
      techniques. One case was FISH+, SISH-, and 1 case was FISH- and SISH+. The
      agreement between the 2 methods was good in cohort 1 (kappa=0.642 [0.428, 0.823])
      and excellent in cohort 2 (kappa=0.963 [0.870, 1.000]). EGFR positivity by FISH
      and SISH was associated with high EGFR protein expression (P<0.001) and EGFR
      mutation (P<0.001). These results validate the use of SISH for assessing EGFR CN
      alterations in NSCLC. The advantage of a permanent result and the possibility of
      bright-field microscopy make SISH an attractive alternative to FISH.

PMID- 23154769
TI  - Hormone receptor expression in invasive breast cancer among Korean women and
      comparison of 3 antiestrogen receptor antibodies: a multi-institutional
      retrospective study using tissue microarrays.
AB  - Estrogen receptor (ER) and progesterone receptor (PR) are prognostic markers of
      breast cancer and predictive markers of response to endocrine therapy. To
      determine rates of ER and PR expression in invasive breast carcinoma among Korean
      women, the Breast Pathology Study Group of the Korean Society of Pathologists
      collected 1198 specimens of invasive breast carcinoma from 6 university
      hospitals. Immunohistochemical analysis was carried out using 1 antibody against
      PR and 3 antibodies against ER (1D5, 6F11, and SP1). Specimens were evaluated
      using the semiquantitative Allred score (scores >2 were considered positive). A
      total of 1077 cases were interpretable for all 3 anti-ER antibodies. ER
      expression was positive in 68.5% of cases using SP1, in 59.6% using 1D5, and in
      58.9% using 6F11. Of 1073 interpretable cases, PR expression was positive in
      51.7% of cases. The frequency distribution of Allred scores revealed a bimodal
      pattern (complete absence of staining or staining in most cells) for both ER and
      PR. Patients with discordant results for 2 different ER antibodies showed a
      median overall survival (between that of double-positive cancer and that of
      double-negative cancer). Our results showed that the rate of hormone receptor
      expression in breast carcinomas among Korean patients did not differ from that of
      western patients. In addition, SP1 was the most sensitive antibody for
      identifying ER expression in tumors. However, further evaluation is needed to
      determine which antibody is the best for selecting patients with discordant
      results who are likely to respond to endocrine therapy.

PMID- 23154770
TI  - The distribution of microscopic melanoma metastases in sentinel lymph nodes:
      implications for pathology protocols.
AB  - The utility of sectioning at multiple levels in the histopathologic analysis of
      sentinel lymph nodes (SLNs) for melanoma and the correlation of metastasis size
      with risk of subsequent metastasis were investigated. Metastatic melanoma was
      identified in SLNs from 91 of 475 (19%) melanoma patients with SLN sampling at
      the Massachusetts General Hospital between 2004 and 2008. All SLNs were evaluated
      by a 9-slide protocol: sets of MART-1, hematoxylin and eosin, and S100 stains at
      3 distinct levels separated by 80 MUm. The location and size of the tumor
      deposits were evaluated in the context of subsequent metastasis and overall
      survival. Of the 91 patients with positive sentinel nodes, all 9 protocol slides
      were available for review in 61 (67%). Eleven of 61 patients had no tumor present
      in the first set of levels; 2 of these patients died of metastatic melanoma.
      Patients in whom 11 or more tumor cells were detected in the sentinel node had a
      greater chance of developing subsequent metastases when compared with patients in
      whom 10 or fewer tumor cells were detected (P=0.05). Of those with either
      metastases >2 mm in diameter or extracapsular extension, 50% developed metastases
      beyond the SLN basin. Eliminating 1 of the 3 levels in the SLN detection protocol
      would have led to a false-negative diagnosis in 18% of patients.

PMID- 23154771
TI  - Molecular genetic evidence supporting the origin of somatic-type malignancy and
      teratoma from the same progenitor cell.
AB  - Occasionally, testicular teratomas have been observed to occur in association
      with somatic-type malignancies. The latter may be seen in the primary germ cell
      tumor or, more commonly, in metastases after chemotherapy. The molecular-genetic
      relationship between the teratoma and the somatic-type malignancy is uncertain.
      We examined 27 pairs of teratoma and somatic-type malignancies in metastatic
      lesions. Interphase fluorescence in situ hybridization (FISH) analysis for 12p
      overexpression and i(12p) was performed on formalin-fixed, paraffin-embedded
      specimens. In addition, we compared the pattern of allelic loss between the
      teratoma and the somatic-type malignancy using 4 microsatellite DNA markers
      (D1S508, interferon-alpha, D13S317, and D18S543). A laser capture microdissection
      technique was used to procure separate tumor components. The somatic-type
      malignancies included adenocarcinoma (13), primitive neuroectodermal tumor (5),
      sarcoma not otherwise specified (5), squamous cell carcinoma (1), chondrosarcoma
      (1), and rhabdomyosarcoma (2). Twenty-one of 27 tumor pairs (78%) showed a
      similar pattern of overexpression of 12p and/or i(12p) in both components. Two of
      the 27 (7%) tumor pairs showed i(12p) only in the teratomatous component, and 4
      of the 27 (15%) tumor pairs showed no abnormalities of chromosome 12p by
      interphase FISH. Eight of the 12 (67%) tumor pairs analyzed had identical
      patterns of loss of heterozygosity in both the teratoma and the somatic-type
      malignancy. Four of the 12 (33%) paired cases showed additional allelic loss at
      the interferon-alpha locus in the somatic-type malignant component only. Our data
      show that the somatic-type malignancies that develop in germ cell tumors have the
      same genetic alterations, detectable by FISH and loss of heterozygosity studies,
      as in the corresponding teratoma. These findings support that the somatic-type
      malignancies within metastases and the teratomas are clonally related and likely
      derived from a common progenitor cell. Interphase FISH can be performed on
      formalin-fixed, paraffin-embedded tissue and is a sensitive method for detecting
      12p overexpression and i(12p), thus aiding in establishing the germ cell origin
      of somatic-type malignancies in this context.

PMID- 23154772
TI  - Histologic criteria and pitfalls in the diagnosis of lymphovascular invasion in
      radical prostatectomy specimens.
AB  - Lymphovascular invasion is a known independent prognostic factor in prostate
      cancer. The objective of this study is to describe reliable morphologic features
      for identification of lymphovascular invasion in prostatectomy specimens and
      avoid misinterpretation of its mimickers. A total of 364 foci of lymphovascular
      invasion were analyzed in 264 slides from 170 prostatectomies. The average tumor
      volume was 25.5%. Tumor emboli were seen inside the tumor (8%), at the front edge
      of the tumor (30%), separated from the tumor (32%), and distant from the tumor
      (30%). Tumor emboli were more frequent per case and more often in an
      extraprostatic location in lymph node-positive cases (P<0.05). One hundred thirty
      four emboli were in a single thin-walled vessel, 227 were in a thin-walled vessel
      next to an artery, and 3 were seen inside an artery. Twenty-eight tumor emboli
      were attached to a vessel wall, 18 had proteinaceous material in the vascular
      lumen, and 14 were surrounded by erythrocytes. The following mimickers were seen:
      retraction artifact and perineural invasion-all cases; cancer impinging upon
      vascular space-45 foci; tangential sections of endothelium-10 foci; displacement
      of benign and collapsed malignant glands-16 and 27 foci, respectively; retraction
      with erythrocytes-3 cases; intravascular degenerating tumor cells-3 foci;
      malignant glands in atrophic ducts-4 foci; and myofibroblastic proliferation in
      thrombosed vessels-2 foci. In 50 stained blocks, CD31 and D2-40 immunostaining
      studies confirmed all lymphovascular invasions diagnosed by hematoxylin and eosin
      staining and demonstrated emboli in 47 lymphatic and 16 blood vessels. In
      summary, the current study identifies features of true lymphovascular invasion
      and how to distinguish them from mimickers on routine hematoxylin and eosin
      sections.

PMID- 23154773
TI  - Conventional chondrosarcoma in a survivor of rhabdoid tumor: enlarging the
      spectrum of tumors associated with SMARCB1 germline mutations.
AB  - SMARCB1 germline mutations mainly predispose to rhabdoid tumors. However, less
      aggressive tumors with a later onset have also been reported in a context of
      SMARCB1 constitutional mutation-that is, schwannomatosis and meningiomatosis. No
      other tumor type has formally been observed in such a context thus far. We report
      on a patient treated for a thoracic malignant rhabdoid tumor at 8 years of age
      who subsequently developed a mandibular conventional chondrosarcoma at 13 years
      of age. Both tumors showed a loss of BAF47 expression. The malignant rhabdoid
      tumor exhibited a large 22q11.2 deletion and an intragenic deletion of SMARCB1
      (exons 1 to 3), thus leading to a biallelic inactivation. A 2.8 Mbp deletion
      encompassing SMARCB1 was found in the germline. This context was a strong
      incentive to investigate SMARCB1 alterations in the second tumor. As expected,
      the chondrosarcoma showed the large 22q11.2 deletion but also an additional
      c.243C>G(p.Tyr18X) premature stop codon in the remaining allele. This report
      relates for the first time a pediatric conventional chondrosarcoma to the wide
      family of SMARCB1-deficient tumors. Moreover, we report here the first case of
      conventional chondrosarcoma arising in a context of constitutional SMARCB1
      deletion and, thus, enlarge the spectrum of this tumor predisposition syndrome.

PMID- 23154774
TI  - Malignant gastrointestinal neuroectodermal tumor showing overlapped
      immunophenotype with synovial sarcoma: CD99 and SOX10 antibodies are useful in
      differential diagnosis.

PMID- 23154776
TI  - Human brain cancer studied by resonance Raman spectroscopy.
AB  - The resonance Raman (RR) spectra of six types of human brain tissues are examined
      using a confocal micro-Raman system with 532-nm excitation in vitro. Forty-three
      RR spectra from seven subjects are investigated. The spectral peaks from
      malignant meningioma, stage III (cancer), benign meningioma (benign), normal
      meningeal tissues (normal), glioblastoma multiforme grade IV (cancer), acoustic
      neuroma (benign), and pituitary adenoma (benign) are analyzed. Using a 532-nm
      excitation, the resonance-enhanced peak at 1548  cm-1 (amide II) is observed in
      all of the tissue specimens, but is not observed in the spectra collected using
      the nonresonance Raman system. An increase in the intensity ratio of 1587 to 1605
      cm-1 is observed in the RR spectra collected from meningeal cancer tissue as
      compared with the spectra collected from the benign and normal meningeal tissue.
      The peak around 1732  cm-1 attributed to fatty acids (lipids) are diminished in
      the spectra collected from the meningeal cancer tumors as compared with the
      spectra from normal and benign tissues. The characteristic band of spectral peaks
      observed between 2800 and 3100  cm-1 are attributed to the vibrations of methyl
      (?CH3) and methylene (?CH2?) groups. The ratio of the intensities of the spectral
      peaks of 2935 to 2880  cm-1 from the meningeal cancer tissues is found to be
      lower in comparison with that of the spectral peaks from normal, and benign
      tissues, which may be used as a distinct marker for distinguishing cancerous
      tissues from normal meningeal tissues. The statistical methods of principal
      component analysis and the support vector machine are used to analyze the RR
      spectral data collected from meningeal tissues, yielding a diagnostic sensitivity
      of 90.9% and specificity of 100% when two principal components are used.

PMID- 23154778
TI  - Experimental validation of a finite-difference model for the prediction of
      transcranial ultrasound fields based on CT images.
AB  - The prevalence of stroke worldwide and the paucity of effective therapies have
      triggered interest in the use of transcranial ultrasound as an adjuvant to
      thrombolytic therapy. Previous studies have shown that 120 kHz ultrasound
      enhanced thrombolysis and allowed efficient penetration through the temporal
      bone. The objective of our study was to develop an accurate finite-difference
      model of acoustic propagation through the skull based on computed tomography (CT)
      images. The computational approach, which neglected shear waves, was compared
      with a simple analytical model including shear waves. Acoustic pressure fields
      from a two-element annular array (120 and 60 kHz) were acquired in vitro in four
      human skulls. Simulations were performed using registered CT scans and a source
      term determined by acoustic holography. Mean errors below 14% were found between
      simulated pressure fields and corresponding measurements. Intracranial peak
      pressures were systematically underestimated and reflections from the
      contralateral bone were overestimated. Determination of the acoustic impedance of
      the bone from the CT images was the likely source of error. High correlation
      between predictions and measurements (R(2) = 0.93 and R(2) = 0.88 for transmitted
      and reflected waves amplitude, respectively) demonstrated that this model is
      suitable for a quantitative estimation of acoustic fields generated during 40-200
      kHz ultrasound-enhanced ischemic stroke treatment.

PMID- 23154780
TI  - Mitochondrial DNA damage mediates hyperoxic dysmorphogenesis in rat fetal lung
      explants.
AB  - BACKGROUND: Numerous studies in cultured cells indicate that damage to
      mitochondrial DNA (mtDNA) dictates cellular responses to oxidant stress, yet the
      consequences of mtDNA damage have not been studied directly in the preterm lung.
      OBJECTIVE: We sought to determine whether hyperoxia-induced fetal lung
      dysmorphogenesis is linked to mtDNA damage and establish mtDNA repair as a
      potential therapeutic approach for treating lung dysplasia in the preterm
      neonate. METHODS: Hyperoxia-induced mtDNA damage was assessed by quantitative
      alkaline gel electrophoresis in normoxic (3% O2) and hyperoxic (21% O2) fetal rat
      lung explants. A fusion protein construct targeting the DNA repair enzyme
      endonuclease III (Endo III) to the mitochondria was used to augment mtDNA repair.
      Fetal lung branching and surfactant protein C (SFPTC) were assessed in these
      tissues. RESULTS: Hyperoxia induced mtDNA damage in lung explants and was
      accompanied by impaired branching morphogenesis and decreased SFPTC mRNA
      expression. Treatment of lung explants with Endo III fusion protein prevented
      hyperoxia-induced mtDNA damage and restored normal branching morphogenesis and
      SFPTC mRNA expression. CONCLUSION: These findings support the concept that mtDNA
      governs cellular responses to oxidant stress in the fetal lung and suggest that
      modulation of mtDNA repair is a potential pharmacologic strategy in the
      prevention of hyperoxic lung injury.

PMID- 23154781
TI  - Risk score for predicting recurrence in patients with ischemic stroke: the
      Fukuoka stroke risk score for Japanese.
AB  - BACKGROUND: Currently, there are only a few risk scores to predict long-term
      recurrence of ischemic stroke and no risk score has been developed for the Asian
      population. The aim of the present study was to develop a new risk score to
      predict 1-year recurrence in Japanese patients with ischemic stroke and compare
      it with the other ones. METHODS: Data used in this analysis were extracted from
      the Fukuoka stroke registry (FSR) database, including 3,067 Japanese patients who
      experienced ischemic stroke. FSR is a multicenter, hospital-based, prospective
      registry of Japanese patients with acute stroke. Associations between potential
      clinical variables that could be involved in the increase of risk and recurrence
      of ischemic stroke within 1 year after initial stroke onset were evaluated using
      univariate and multivariate analyses. To calculate risk scores, weighted points
      proportionally based on standardized coefficient values were assigned to
      variables that were identified to be significant risks for recurrence by
      multivariate analysis. The Hosmer-Lemeshow goodness-of-fit test was used to test
      agreement between a predicted outcome using a model and an actual observed
      outcome. Kaplan-Meier analysis was used to estimate average cumulative recurrence
      rates within three risk groups. Intergroup comparisons in recurrence rate among
      the risk groups were performed using a log-rank test. RESULTS: Univariate and
      multivariate analyses identified nine significant predictors for 1-year
      recurrence, to which we assigned the following points: age (65-74 years, 1 point;
      >=75 years, 2 points), hypertension (1 point), diabetes mellitus (1 point),
      smoker (1 point), atrial fibrillation (1 point), cardiac diseases (1 point),
      chronic kidney disease (1 point), nonlacunar stroke (1 point), and previous
      ischemic stroke (2 points). The Hosmer-Lemeshow goodness-of-fit test demonstrated
      good agreement between the observed and predicted recurrence rate (chi(2) = 2.30,
      p = 0.97). The ROC curve for the risk score models showed acceptable discriminant
      power with a C-statistic of 0.636 (95% confidence interval: 0.573-0.698). Trends
      toward increased risk of recurrence with higher scores were observed. The 1-year
      recurrence rates were 2.93, 5.83 and 7.96% in low- (<=3 points), intermediate (4
      5 points), and high-risk groups (>=6 points), respectively. Kaplan-Meier curves
      with log-rank test showed a significant difference in recurrence among the three
      risk groups (p < 0.0001). CONCLUSIONS: A new risk score was developed and
      successfully validated. Our results suggest that this simple risk score enables
      clinicians to assess 1-year recurrence risk in Japanese patients with ischemic
      stroke.

PMID- 23154782
TI  - Isolation of mouse mesenchymal stem cells on the basis of expression of Sca-1 and
      PDGFR-alpha.
AB  - Platelet-derived growth factor receptor alpha (PDGFR-alpha) and stem cell antigen
      1 (Sca-1) have recently been identified as selective markers of mouse mesenchymal
      stem cells (MSCs). PDGFR-alpha(+)Sca-1(+) (PalphaS) MSCs have augmented growth
      potential and robust tri-lineage differentiation compared with standard culture
      selected MSCs. In addition, the selective isolation of PalphaS MSCs avoids
      cellular contamination that can complicate other methods. Here we describe in
      detail our protocol to isolate PalphaS MSCs using flow cytometry. In brief, the
      tibia and femora are isolated and crushed using a pestle and mortar. The crushed
      bones are then chopped and incubated for 1 h at 37  degrees C in 20 ml of DMEM
      containing 0.2% (wt/vol) collagenase. The cell suspension is filtered before red
      blood cell lysis and incubated with the following antibodies: allophycocyanin
      (APC)-conjugated PDGFR-alpha, FITC-conjugated Sca-1, phycoerythrin (PE)
      conjugated CD45 and Ter119. Appropriate gates are constructed on a cell sorter to
      exclude dead cells and lineage (CD45(+)Ter-119(+))-positive cells. Approximately
      10,000 PalphaS MSCs may then be isolated per mouse. The total protocol takes ~7 h
      to complete.

PMID- 23154783
TI  - Exosome-mediated delivery of siRNA in vitro and in vivo.
AB  - The use of small interfering RNAs (siRNAs) to induce gene silencing has opened a
      new avenue in drug discovery. However, their therapeutic potential is hampered by
      inadequate tissue-specific delivery. Exosomes are promising tools for drug
      delivery across different biological barriers. Here we show how exosomes derived
      from cultured cells can be harnessed for delivery of siRNA in vitro and in vivo.
      This protocol first describes the generation of targeted exosomes through
      transfection of an expression vector, comprising an exosomal protein fused with a
      peptide ligand. Next, we explain how to purify and characterize exosomes from
      transfected cell supernatant. Next, we detail crucial steps for loading siRNA
      into exosomes. Finally, we outline how to use exosomes to efficiently deliver
      siRNA in vitro and in vivo in mouse brain. Examples of anticipated results in
      which exosome-mediated siRNA delivery is evaluated by functional assays and
      imaging are also provided. The entire protocol takes ~3 weeks.

PMID- 23154785
TI  - Bifunctional heterometallic Ln3+-Gd3+ (Ln = Eu, Tb) hybrid silica microspheres:
      luminescence and MRI contrast agent property.
AB  - A novel series of homometallic and heterometallic lanthanide (Eu(3+)(Tb(3+))
      Gd(3+)) hybrid silica microspheres (EDTA-(Eu(Tb)-Gd)-TTA-SiO(2)) are synthesized
      with 2-thenoyltrifluoroacetone (TTA) functionalized silane and
      ethylenediaminetetraacetic acid (EDTA) by sol-gel process, whose physical
      characterization are carried out and especially the luminescence and the magnetic
      resonance imaging (MRI) contrast agent properties are discussed. These hybrids
      present uniform silica microsphere morphology with particle size of 1 MUm.
      Comparing to the homometallic hybrid silica microsphere EDTA-Ln-TTA-SiO(2)
      without Gd(3+) ion, the heterometallic hybrid silica microspheres EDTA-Eu-Gd-TTA
      SiO(2) exhibit stronger luminescent intensity, longer lifetime and higher
      luminescent quantum efficiency, which is due to the fact that inert ion Gd(3+)
      can enhance the luminescence of the Eu(3+) or Tb(3+) within the hybrid system. In
      addition, the MRI relaxivity of the heterometallic lanthanide hybrid silica
      microspheres in water is assessed, showing a lower T1 relaxation rate than
      homometallic gadolinium hybrid one (EDTA-Gd-TTA-SiO(2)). Both of them show higher
      T1 relaxation rate than the conventional Gd chelate of diethylenetriamine
      pentaacetic acid. These bifunctional hybrid materials exhibit both luminescent
      and MRI magnetic contrast agent properties, whose further investigation can be
      expected to have potential application in practical fields such as optical
      storage and sensors, etc.

PMID- 23154784
TI  - The use of phage display to generate conformation-sensor recombinant antibodies.
AB  - We describe a phage display approach that we have previously used to generate
      conformation-sensor antibodies that specifically recognize and stabilize the
      oxidized, inactive conformation of protein tyrosine phosphatase 1B (PTP1B). We
      use a solution-based panning and screening strategy conducted in the presence of
      reduced active PTP1B, which enriches antibodies to epitopes unique to the
      oxidized form while excluding antibodies that recognize epitopes common to
      oxidized and reduced forms of PTP1B. This strategy avoids conventional solid
      phase immobilization owing to its inherent potential for denaturation of the
      antigen. In addition, a functional screening strategy selects single-chain
      variable fragments (scFvs) directly for their capacity for both specific binding
      and stabilization of the target enzyme in its inactive conformation. These
      conformation-specific scFvs illustrate that stabilization of oxidized PTP1B is an
      effective strategy to inhibit PTP1B function; it is possible that this approach
      may be applicable to the protein tyrosine phosphatase (PTP) family as a whole.
      With this protocol, isolation and characterization of specific scFvs from immune
      responsive animals should take ~6 weeks.

PMID- 23154786
TI  - Detection of meniscal tears by arthroscopy and arthrotomy in dogs with cranial
      cruciate ligament rupture: a retrospective, cohort study.
AB  - OBJECTIVES: To evaluate and compare detection of meniscal tears associated with
      cranial cruciate ligament insufficiency by either arthroscopy or arthrotomy.
      METHODS: A retrospective, cohort study was completed with stifles (n = 531) of
      dogs with cranial cruciate ligament rupture. Either a medial parapatellar
      arthrotomy or an arthroscopy procedure was performed and groups were compared for
      significant differences in meniscal tears detected using logistic regression
      analysis. RESULTS: Arthroscopy was performed on 58.8% and arthrotomy on 41.2% of
      the stifles. In total, 44.4% of the examined stifles had meniscal tears. Meniscal
      tears were found in 38.8% of the stifles examined by arthrotomy, and 48.4% of
      those examined by arthroscopy. Overall, the rate of detection of a meniscal tear
      was significantly different (p = 0.019) between the groups, and meniscal tears
      were observed more frequently by arthroscopy than by arthrotomy (odds ratio 1.54;
      95% confidence interval 1.07 - 2.22). CLINICAL SIGNIFICANCE: These results
      suggest that arthroscopy may be more sensitive than arthrotomy for detection of
      meniscal pathology in clinical patients. However, these results must be
      interpreted with caution since this was a retrospective study. Randomized
      prospective clinical studies are required to further test this hypothesis.

PMID- 23154787
TI  - Higher dietary intakes of potassium, calcium and magnesium are associated with a
      reduced risk of developing vascular dementia.

PMID- 23154788
TI  - Microlesion effect as a predictor of the effectiveness of subthalamic deep brain
      stimulation for Parkinson's disease.
AB  - BACKGROUND: Microlesion effect (MLE) is a commonly observed phenomenon after
      electrode insertion into the subthalamic nucleus (STN) for deep brain stimulation
      (DBS). OBJECTIVES: The aim of this study was to determine the presence of the MLE
      in the early postoperative period and the relationship between MLE and STN DBS.
      METHODS: 74 patients with Parkinson's disease were included in this study. Motor
      symptoms were evaluated preoperatively, within 48 h after electrode implantation
      and at 6 months with United Parkinson's Disease Rating Scale part III (UPDRS
      III). According to the improvement level with MLE, all participants were
      stratified into three groups: (1) less than 20%; (2) 20-40%, and (3) more than
      40% in OFF medication states. The degree of improvement in UPDRS-III with DBS ON
      for each MLE group was assessed at the 6-month follow-up. Regression analysis was
      applied for the evaluation of the relationship between MLE and improvement with
      DBS ON. RESULTS: Mean results in UPDRS-III with the MLE in ON and OFF medication
      states were 22.1 +/- 10.5 and 42.1 +/- 14 points, respectively. At the 6-month
      follow-up, with active stimulation, results tended to further ameliorate to 14.6
      (59.4%) points in ON and 20.8 (55.3%) in OFF. Mean improvement in MLE groups
      were: 33.6% group 1, 47.5% group 2 and 61.4% group 3. Regression analysis
      revealed a positive correlation between the MLE and results at 6 months with DBS
      ON. CONCLUSION: Results proved the presence of MLE in the early postoperative
      period. Furthermore, a positive correlation between MLE and improvement degree
      with active stimulation was observed.

PMID- 23154789
TI  - Risk of bleeding complications after preoperative antiplatelet withdrawal versus
      continuing antiplatelet drugs during transurethral resection of the prostate and
      prostate puncture biopsy: a systematic review and meta-analysis.
AB  - OBJECTIVE: To systematically evaluate the risk of antiplatelet drugs (APs) on
      bleeding complications in urological surgery. METHODS: Studies were sought and
      included in this review if they were clinical controlled trials and involved
      transurethral resection of the prostate (TURP) and prostate puncture biopsy
      (PPB), which compared preoperative AP withdrawal (control group) with continuing
      APs (experimental group) and revealed bleeding complications as outcomes. A
      literature search was conducted of the electronic databases PubMed, Ovid,
      ScienceDirect and Embase for studies published between 1990 and 2012. Two
      reviewers independently screened the studies for eligibility, evaluated the
      quality and extracted the data from the eligible studies, with confirmation by
      cross-checking. There was evidence of publication bias based on Egger's test and
      funnel plot. Data were processed using Cochrane Review Manager 5.0 software.
      RESULTS: Nine studies involving 3,145 cases met the inclusion criteria and were
      included in the meta-analysis. The baselines of patients' characteristics were
      comparable in all studies. The meta-analysis results showed that no differences
      were found in risk of bleeding after (1) TURP (OR 1.26, 95% CI 0.80-2.00, p =
      0.32) or (2) PPB (OR 0.89, 95% CI 0.45-1.76, p = 0.73). CONCLUSION: Preoperative
      APs do not raise the risk of surgical bleeding complications in prostatectomy and
      PPB. Because of few studies and small samples, more high-quality trials with
      larger samples and longer follow-ups are proposed.

PMID- 23154790
TI  - Surfactant modification of aggregation-induced emission material as biocompatible
      nanoparticles: facile preparation and cell imaging.
AB  - Water soluble and biocompatible fluorescent organic nanoparticles based on
      aggregation-induced emission (AIE) material were facilely prepared by mixing AIE
      material and surfactant. The utilization of such fluorescent organic
      nanoparticles for cell imaging applications was further explored.

PMID- 23154791
TI  - Dynamic tissue perfusion measurement: a new tool for characterizing renal
      perfusion in renal cell carcinoma patients.
AB  - INTRODUCTION: Renal cell carcinoma (RCC) is characterized by intense angiogenesis
      with hyperexpression of proangiogenic factors. This study explored the potential
      of dynamic tissue perfusion measurement (DTPM) to detect differences in tissue
      perfusion between kidneys with RCC and corresponding healthy kidneys. PATIENTS
      AND METHODS: 30 patients with unilateral, histologically confirmed RCC underwent
      DTPM by color Doppler ultrasound. Before scheduled surgery, Doppler ultrasound
      data were acquired from four transverse areas of the affected kidney and the
      contralateral healthy kidney. Doppler ultrasound data were recorded over a 10
      second period and characteristic tissue perfusion parameters were determined.
      RESULTS: The kidneys with RCC displayed characteristic changes in perfusion
      parameters. A significant increase in signal intensity and a significant decrease
      in flow resistance were noted. A combination of several DTPM parameters was used
      to distinguish correctly between kidneys bearing RCC or healthy kidneys with up
      to 75% accuracy. There was no association between the perfusion parameters and
      the pathological characteristics of the respective tumors. CONCLUSIONS: DTPM is a
      promising tool for the evaluation of whole-organ tissue perfusion. This study
      demonstrates the feasibility of performing DTPM measurements in kidneys bearing
      RCC lesions. In tumors that are characterized by extensive neovascularization,
      this method has the potential to be a valuable diagnostic tool.

PMID- 23154792
TI  - Directed surface attachment of nanomaterials via coiled-coil-driven self
      assembly.
AB  - Numerous nanoscale devices and materials have been fabricated in recent years
      using a variety of biological scaffolds. However, the interfacing of these
      devices and materials into existing circuits and ordered arrays has proved
      problematic. Here, we describe a simple solution to this problem using self
      assembly of the peptide coiled-coil heterodimer ACID:BASE to immobilize M13
      bacteriophage particles to specific locations on a patterned gold surface.
      Surface plasmon resonance demonstrated that free ACID peptides will assemble onto
      a surface derivatized with BASE. We then displayed the ACID peptide on the pIX
      coat protein of M13 and showed that these phage particles permit formation of the
      coiled-coil resulting in specific surface attachment. The ACID:immobilized BASE
      affinities appear to be similar for free peptide and phage-displayed ACID.
      Finally, we fabricated two gold electrodes, separated by a 200 nm gap, coated one
      of them with BASE and showed that this allows localization of the M13:ACID onto
      the functionalized electrode.

PMID- 23154793
TI  - Postoperative cerebral white matter damage associated with cerebral
      hyperperfusion and cognitive impairment after carotid endarterectomy: a diffusion
      tensor magnetic resonance imaging study.
AB  - BACKGROUND: Cerebral hyperperfusion after carotid endarterectomy (CEA), even when
      asymptomatic, often impairs cognitive function. However, conventional magnetic
      resonance (MR) imaging rarely demonstrates structural brain damage associated
      with postoperative cognitive impairment. MR diffusion tensor imaging (DTI) is
      potentially more sensitive for detection of white matter damage. Among the common
      parameters derived by DTI, fractional anisotropy (FA) is a marker of tract
      integrity, and mechanical disruption of axonal cylinders and loss of continuity
      of myelin sheaths may be responsible for reduced FA in white matter. The purpose
      of the present study was to determine whether postoperative cerebral white matter
      damage that can be detected by FA derived by DTI is associated with cerebral
      hyperperfusion after CEA and correlates with postoperative cognitive impairment.
      METHODS: In 70 patients undergoing CEA for ipsilateral internal carotid artery
      stenosis (>=70%), cerebral blood flow (CBF) was measured using single-photon
      emission computed tomography (SPECT) before and immediately after CEA and on
      postoperative day 3. FA values in cerebral white matter were assessed using DTI
      before and 1 month after surgery. These values were normalized and analyzed using
      statistical parametric mapping 5. In each corresponding voxel in the pre- and
      postoperative normalized FA maps of each patient, a postoperative FA value minus
      a preoperative FA value was calculated, and a voxel with postoperatively reduced
      FA was defined based on data obtained from healthy volunteers. The number of
      voxels with postoperatively reduced FA was calculated and defined as the volume
      with postoperatively reduced FA. Neuropsychological testing, consisting of the
      Wechsler Adult Intelligence Scale Revised, the Wechsler Memory Scale and the Rey
      Osterreith Complex Figure test, was also performed preoperatively and after the
      first postoperative month. Postoperative cognitive impairment on
      neuropsychological testing in each patient was defined based on data obtained
      from patients with asymptomatic unruptured cerebral aneurysms. RESULTS: Post-CEA
      hyperperfusion on brain perfusion SPECT (CBF increase >=100% compared with
      preoperative values) and postoperative cognitive impairment on neuropsychological
      testing were observed in 11 (16%) and 9 patients (13%), respectively. The volume
      with postoperatively reduced FA in cerebral white matter ipsilateral to surgery
      was significantly greater in patients with post-CEA hyperperfusion than in those
      without (p < 0.0001). This volume in cerebral white matter ipsilateral to surgery
      was also significantly associated with postoperative cognitive impairment (95%
      confidence interval, 1.559-8.853; p = 0.0085). CONCLUSIONS: Cerebral
      hyperperfusion after CEA results in postoperative cerebral white matter damage
      that correlates with postoperative cognitive impairment.

PMID- 23154794
TI  - Switchable skin window induced by optical clearing method for dermal blood flow
      imaging.
AB  - Optical imaging techniques have shown tremendous potential for assessing
      cutaneous microcirculation, but the imaging depth and contrast is limited by the
      strong scattering of skin. Current skin windows have to be fulfilled by surgical
      operation and suffer from some side effects. In this study, a switchable skin
      window was developed by topical application of an optical clearing agent (OCA)
      and saline on rat skin in vivo. The validity of the skin window was evaluated by
      the laser speckle contrast imaging technique, and the safety of OCA to the body
      was tested through histologic examinations. The results indicated that
      administration of OCA or saline on rat skin in vivo can open or close the window
      of skin repeatedly for three days. With the repair effect of hyaluronic acid and
      Vaseline, it is able to repeatedly visualize the dermal blood vessels and flow
      distribution. Long-term observation shows that there is no abnormal reflection in
      micro-structure, body weight, organ coefficients, histopathologic lesions, or
      toxic reactions compared with a control group. This switchable window will
      provide an effective tool not only for cutaneous microcirculation with laser
      speckle contrast imaging, but also for diagnosis and treatment of peripheral
      vascular diseases, including tumor research with various optical imaging
      techniques.

PMID- 23154796
TI  - Thalamotomy as a treatment option for tremor after ineffective deep brain
      stimulation.
AB  - BACKGROUND: As the number of deep brain stimulation (DBS) surgeries increases,
      complications from malpositioned electrodes, tolerance to stimulation and loss of
      efficacy have also increased. Our objective was to assess thalamotomy as a
      salvage treatment option after ineffective DBS. METHODS: A retrospective chart
      analysis of patients who underwent ipsilateral stereotactic thalamotomy after an
      ineffective ventrointermediate nucleus DBS procedure was undertaken. Patient
      outcome was based on follow-up visit chart notes, and a nonvalidated patient
      telephone questionnaire to assess patients' perception of tremor and functional
      ability after thalamotomy. RESULTS: Six patients with essential tremor and 1 with
      tremor-predominant Parkinson's disease met our inclusion criteria. Thalamotomies
      were undertaken for ineffective DBS due to dysarthria and paresthesias with
      programming in 2 patients, tremor that failed to respond to increased DBS despite
      a lack of side effects in 2 patients, malpositioned electrode in 2 patients, and
      sudden loss of DBS efficacy following eye surgery in 1 patient. Following
      thalamotomy, 3 patients reported improvement in symptoms and function, 3 patients
      reported improvement in symptoms that were not reflected in functional
      improvement, and 1 patient reported no improvement in symptoms or function.
      CONCLUSION: Thalamotomy may provide a viable salvage solution in patients who
      fail to respond to DBS due to complications such as malpositioned electrodes,
      tolerance to stimulation or loss of efficacy.

PMID- 23154795
TI  - Impact of margin size on the predicted risk of radiogenic second cancers
      following proton arc therapy and volumetric modulated arc therapy for prostate
      cancer.
AB  - We previously determined that the predicted risk of radiogenic second cancer in
      the bladder and rectum after proton arc therapy (PAT) was less than or equal to
      that after volumetric modulated arc therapy (VMAT) with photons, but we did not
      consider the impact of margin size on that risk. The current study was thus
      conducted to evaluate margin size's effect on the predicted risks of second
      cancer for the two modalities and the relative risk between them. Seven treatment
      plans with margins ranging from 0 mm in all directions to 6 mm posteriorly and 8
      mm in all other directions were considered for both modalities. We performed risk
      analyses using three risk models with varying amounts of cell sterilization and
      calculated ratios of risk for the corresponding PAT and VMAT plans. We found that
      the change in risk with margin size depended on the risk model but that the
      relative risk remained nearly constant with margin size, regardless of the amount
      of cell sterilization modeled. We conclude that while margin size influences the
      predicted risk of a second cancer for a given modality, it appears to affect both
      modalities in roughly equal proportions so that the relative risk between PAT and
      VMAT is approximately equivalent.

PMID- 23154799
TI  - Direct coupling of nitriles and aniline to form the triazapentadiene species
      [upper bond 1 start]Rh(III){NH=C(R)N(Ph)C(R=N[upper bond 1 end]H}.
AB  - The facile and high-yield reaction between aniline and cis-positioned nitriles of
      [((t)bpy)(2)Rh(NCR)(2)][OTf](3) [R = Me (2), Ph (3); (t)bpy = 4,4'-di-tert-butyl
      2,2'-bipyridine; OTf = CF(3)SO(3)(-)] produces the Rh(III)-triazapentadiene
      species [((t)bpy)(2)[upper bond 1 start]Rh{NH=C(R)N(Ph)C(R=N[upper bond 1
      end]H}][OTf](3) [R = Me (4), Ph (5)]. It represents the first example of direct
      coupling between two RCN ligands and a primary amine to form this type of
      metallacycle. X-ray structures of 2 and 4 are reported.

PMID- 23154808
TI  - Evolution of genetic and genomic features unique to the human lineage.
AB  - Given the unprecedented tools that are now available for rapidly comparing
      genomes, the identification and study of genetic and genomic changes that are
      unique to our species have accelerated, and we are entering a golden age of human
      evolutionary genomics. Here we provide an overview of these efforts, highlighting
      important recent discoveries, examples of the different types of human-specific
      genomic and genetic changes identified, and salient trends, such as the
      localization of evolutionary adaptive changes to complex loci that are highly
      enriched for disease associations. Finally, we discuss the remaining challenges,
      such as the incomplete nature of current genome sequence assemblies and
      difficulties in linking human-specific genomic changes to human-specific
      phenotypic traits.

PMID- 23154809
TI  - Adaptive evolution: evaluating empirical support for theoretical predictions.
AB  - Adaptive evolution is shaped by the interaction of population genetics, natural
      selection and underlying network and biochemical constraints. Variation created
      by mutation, the raw material for evolutionary change, is translated into
      phenotypes by flux through metabolic pathways and by the topography and dynamics
      of molecular networks. Finally, the retention of genetic variation and the
      efficacy of selection depend on population genetics and demographic history.
      Emergent high-throughput experimental methods and sequencing technologies allow
      us to gather more evidence and to move beyond the theory in different systems and
      populations. Here we review the extent to which recent evidence supports long
      established theoretical principles of adaptation.

PMID- 23154812
TI  - Surgical management of radial head luxation in a dog using an external skeletal
      traction device.
AB  - A five-month-old Airedale Terrier was presented with a history of right thoracic
      limb lameness. Clinical and radiographic examinations revealed caudolateral
      luxation of the right radial head. Surgical intervention involved an oblique
      proximal radial osteotomy and gradual craniomedial traction of the radial head
      using an external skeletal fixator (ESF) incorporating a traction device. The
      radial head was gradually reduced over 16 days. After radiographic confirmation
      of appropriate radial head reduction, a consolidation phase followed, with
      removal of the traction ESF after 24 days. Follow-up radiographs documented
      remodelling of the radial head. Clinical follow-up three years postoperatively
      revealed nearly normal ground reaction forces. Activity was unrestricted and
      there was no requirement for analgesic medications.

PMID- 23154811
TI  - Asymmetric synthesis of 2,3-dihydroquinolin-4-one derivatives catalyzed by a
      chiral bisguanidium salt.
AB  - Worth its salt: An orgnaocatalytic asymmetric intramolecular aza-Michael reaction
      and one-pot bromination reaction of activated alpha,beta-unsaturated ketones have
      been realized using a chiral bisguanidium salt. Optically enriched 2-aryl- and 2
      alkyl-substituted dihydroquinones and brominated dihydroquinones could be
      obtained (up to 99% yield and 99% ee for the aza-Michael reaction; and up to 95%
      yield, 96:4 d.r., and 95% ee for the bromination reaction).

PMID- 23154810
TI  - Human mitochondrial DNA: roles of inherited and somatic mutations.
AB  - Mutations in the human mitochondrial genome are known to cause an array of
      diverse disorders, most of which are maternally inherited, and all of which are
      associated with defects in oxidative energy metabolism. It is now emerging that
      somatic mutations in mitochondrial DNA (mtDNA) are also linked to other complex
      traits, including neurodegenerative diseases, ageing and cancer. Here we discuss
      insights into the roles of mtDNA mutations in a wide variety of diseases,
      highlighting the interesting genetic characteristics of the mitochondrial genome
      and challenges in studying its contribution to pathogenesis.

PMID- 23154813
TI  - A new paradigm for the diagnosis and management of unknown primary tumors of the
      head and neck: a role for transoral robotic surgery.
AB  - OBJECTIVES/HYPOTHESIS: In 2% to 3% of patients with cancer metastatic to cervical
      lymph nodes, a primary tumor will not be found despite exhaustive diagnostic
      efforts. The treatment for these patients includes cervical lymphadenectomy
      followed by radiation to areas with increased risk of harboring a mucosal
      primary. Wide-field radiation therapy increases the incidence of xerostomia and
      dysphagia. Localizing a primary tumor has thus both therapeutic and quality-of
      life implications, allowing possible complete surgical excision, concentrated
      radiation therapy, and potential deintensification of adjuvant therapy. With
      improved visualization and freedom of motion, transoral robotic surgery (TORS) is
      an innovative surgical modality that allows resection of oropharyngeal subsites
      with minimal morbidity. STUDY DESIGN: Retrospective chart review. METHODS: Ten
      patients with unknown primary tumors of the head and neck were identified. All
      patients underwent a cervical biopsy, positron-emission tomography/computed
      tomography, formal endoscopy, and bilateral tonsillectomy. When the initial
      endoscopy and biopsies did not localize a primary tumor, all patients underwent
      transoral robotic base of tongue resection. RESULTS: Evaluation of the patients'
      oropharyngeal mucosa using the robot did not reveal an obvious lesion and no
      palpable tumors were appreciated in the resected specimens. In 9/10 (90%)
      patients, pathologic examination revealed invasive squamous cell carcinoma (SCCA)
      with a mean diameter of 0.9 cm. CONCLUSIONS: Unknown primary SCCA presents a
      diagnostic challenge to the head and neck surgeon. We present a small series of
      tumors that would have been treated as unknown primaries under traditional
      diagnostic and therapeutic algorithms. TORS base of tongue resection identified
      primary tumors in 90% patients with minimal morbidity.

PMID- 23154815
TI  - Effects of deep brain stimulation in the caudal zona incerta on verbal fluency.
AB  - BACKGROUND: Deep brain stimulation (DBS) of the caudal zona incerta (cZi) is a
      relatively unexplored and promising treatment in patients with severe essential
      tremor (ET). Preliminary data further indicate that the ability to produce
      language may be slightly affected by the treatment. OBJECTIVE: To evaluate the
      effects on verbal fluency following cZi DBS in patients with ET. METHOD:
      Seventeen consecutive patients who had undergone DBS of the cZi for ET were
      tested regarding verbal fluency before surgery, 3 days after surgery and after 1
      year. Ten patients were also evaluated by comparing performance on versus off
      stimulation after 1 year. RESULTS: The total verbal fluency score decreased
      slightly, but significantly, from 22.7 (SD = 10.9) before surgery to 18.1 (SD =
      7.5) 3 days after surgery (p = 0.036). After 1 year the score was
      nonsignificantly decreased to 20.1 (SD = 9.7, p = 0.2678). There was no
      detectable difference between stimulation on and off after 1 year. CONCLUSION:
      There was a tendency of an immediate and mostly transient postoperative decline
      in verbal fluency following cZi DBS for ET. In some of the patients this
      reduction was, however, more pronounced and also sustained over time.

PMID- 23154814
TI  - Angiotensin II induces TSLP via an AT1 receptor/NF-KappaB pathway, promoting Th17
      differentiation.
AB  - BACKGROUND: Adaptive immunity plays a critical role in atherosclerosis and
      hypertension. T helper 17 (Th17) cells, as a new T-cell lineage, are involved in
      cardiovascular diseases. Dendritic cells (DCs) are the professional antigen
      presenting cells with the pivotal role in orchestrating adaptive immunity. Thymic
      stromal lymphopoietin (TSLP) can activate DCs and trigger adaptive immune
      responses. What the role of TSLP in atherosclerosis and hypertension has not been
      investigated. METHODS AND RESULTS: We measured the expression of TSLP in primary
      rat vascular smooth muscle cells (VSMCs) exposed to angiotensin II (Ang II) and
      evaluated the capacity of TSLP induced by Ang II to induce the differentiation of
      Th17 Cells. We then sought to identify the involved upstream regulatory
      mechanisms. We found that VSMCs express TSLP in response to Ang II in an AT1
      receptor/NF-KappaB manner. TSLP can induce the differentiation of Th17 Cells by
      triggering DCs. CONCLUSION: Through DC activation, Ang II-induced TSLP enhances
      Th17-driven immune response in atherosclerosis and hypertension.

PMID- 23154816
TI  - High yield transfer of ordered nanowire arrays into transparent flexible polymer
      films.
AB  - The factors affecting transfer of nanowire arrays from their substrates into
      flexible PDMS films have been systematically investigated. Experiments were
      carried out on gallium phosphide nanowires with a standard length of 10 MUm with
      varying pitch (0.2-1.5 MUm). The important factors were found to be penetration
      of the PDMS within the nanowire arrays and the strength/rigidity of the PDMS
      film. The PDMS penetration between wires in the arrays is affected by both the
      viscosity of the PDMS solution and the presence of air pockets trapped within
      nanowire arrays, particularly at small pitches. Dilution with hexane and curing
      in a vacuum desiccator solve the wire penetration problem, and an increase in
      cure/base ratio increases the rigidity and strength of the PDMS. The procedures
      for preparation and deposition of the PDMS solution are optimized and a high
      yield, up to 95%, of wire transfer across a range of nanowire pitches has been
      obtained.

PMID- 23154817
TI  - Enhanced photocoagulation with catheter-based diffusing optical device.
AB  - A novel balloon catheter-based diffusing optical device was designed and
      evaluated to assist in treating excessive menstrual bleeding. A synthetic fused
      silica fiber was micro-machined precisely to create scattering segments on a 25
      mm long fiber tip for uniform light distribution. A visible wavelength
      (lambda=532  nm) was used to specifically target the endometrium due to the high
      vascularity of the uterine wall. Optical simulation presented 30% wider
      distribution of photons along with approximately 40% higher irradiance induced by
      addition of a glass cap to the diffuser tip. Incorporation of the optical
      diffuser with a polyurethane balloon catheter considerably enhanced coagulation
      depth and area (i.e., 3.5 mm and 18.9  cm2 at 1 min irradiation) in tissue in
      vitro. The prototype device demonstrated the coagulation necrosis of 2.8+/-1.2 
      mm (n=18) and no thermal damage to myometrium in in vivo caprine models. A
      prototype 5 cm long balloon catheter-assisted optical diffuser was also evaluated
      with a cadaveric human uterus to confirm the coagulative response of the uterine
      tissue as well as to identify the further design improvement and clinical
      applicability. The proposed catheter-based diffusing optical device can be a
      feasible therapeutic tool to photocoagulate endometrial cell layers in an
      efficient and safe manner.

PMID- 23154818
TI  - Diagnosis: clinician's gut feeling helps detect children with serious infection.

PMID- 23154819
TI  - Microfluidic ultralow interfacial tensiometry with magnetic particles.
AB  - We describe a technique that measures ultralow interfacial tensions using
      paramagnetic spheres in a co-flow microfluidic device designed with a magnetic
      section. Our method involves tuning the distance between the co-flowing interface
      and the magnet's center, and observing the behavior of the spheres as they
      approach the liquid-liquid interface-the particles either pass through or are
      trapped by the interface. Using threshold values of the magnet-to-interface
      distance, we make estimates of the two-fluid interfacial tension. We demonstrate
      the effectiveness of this technique for measuring very low interfacial tensions,
      O(10(-6)-10(-5)) N m(-1), by testing solutions of different surfactant
      concentrations, and we show that our results are comparable with measurements
      made using a spinning drop tensiometer.

PMID- 23154822
TI  - Surgical repair of a tibial fracture in a two-week-old grey seal (Halichoerus
      grypus).
AB  - OBJECTIVE: To report the successful management of a suspected infected tibial
      fracture in a common grey seal. STUDY DESIGN: Case report. ANIMAL: Female common
      grey seal (Halichoerus grypus), 2 weeks old, 20 kg. METHODS: A closed, complete,
      transverse fracture of the left tibial distal diaphysis was debrided, reduced and
      stabilized using a string-of-pearls (SOP) locking plate covered with
      polymethylmethacrylate impregnated with gentamicin. Fracture of the ipsilateral
      fibula was left untreated. Postoperative radiographs were obtained immediately,
      and at 10 days, three weeks, and six weeks post-surgery, and a computed
      tomographic examination was performed 2.5 months post- surgery. A species
      specific progressive rehabilitation programme was conducted. RESULTS: Bone
      healing of both fractures and absence of injury of the distal tibial growth plate
      were evident on the 2.5 month follow-up examination, and also full range-of
      motion of the flipper was preserved and no lameness or difficulty with swimming
      and hunting were detected. On computed tomography, signs of chronic left
      coxofemoral and ilial wing trauma were incidentally detected. The seal was
      released three months postoperatively. CONCLUSION: A transverse infected distal
      fracture of the tibia and fibula in a young common grey seal was successfully
      managed with the combination of single SOP plating of the tibia, local antibiotic
      release and a specific rehabilitation programme. CLINICAL RELEVANCE: Surgical
      treatment of a long-bone fracture in a wild immature grey seal was successful
      with a combination of techniques adapted to the species.

PMID- 23154823
TI  - Rolled-up magnetic microdrillers: towards remotely controlled minimally invasive
      surgery.
AB  - Self-folded magnetic microtools with sharp ends are directed at enabling drilling
      and related incision operations of tissues, ex vivo, in a fluid with a viscosity
      similar to that of blood. These microtools change their rotation from a
      horizontal to a vertical one when they are immersed into a rotational magnetic
      field. Novel self-assembly paradigms with magnetic materials can enable the
      creation of remotely controlled and mass-produced tools for potential
      applications in minimally invasive surgery.

PMID- 23154824
TI  - Nanoepitaxy of GaAs on a Si(001) substrate using a round-hole nanopatterned SiO2
      mask.
AB  - GaAs is grown by metal-organic vapor-phase epitaxy on a 55 nm round-hole
      patterned Si substrate with SiO(2) as a mask. The threading dislocations, which
      are stacked on the lowest energy facet plane, move along the SiO(2) walls,
      reducing the number of dislocations. The etching pit density of GaAs on the 55 nm
      round-hole patterned Si substrate is about 3.3 * 10(5) cm(-2). Compared with the
      full width at half maximum measurement from x-ray diffraction and
      photoluminescence spectra of GaAs on a planar Si(001) substrate, those of GaAs on
      the 55 nm round-hole patterned Si substrate are reduced by 39.6 and 31.4%,
      respectively. The improvement in material quality is verified by transmission
      electron microscopy, field-emission scanning electron microscopy, Hall
      measurements, Raman spectroscopy, photoluminescence, and x-ray diffraction
      studies.

PMID- 23154827
TI  - Dissection of the potential characteristic of miRNA-miRNA functional synergistic
      regulations.
AB  - MicroRNAs (miRNAs), as master gene regulators, control various cellular processes
      through the post-transcriptional regulatory network. miRNA synergetic regulations
      are gradually identified by experimental or computational evidence. However, the
      potential characteristic underlying miRNA synergism remains a mystery. Based on
      the constructed miRNA-miRNA functional synergetic networks (MFSNs), we attempted
      to systematically dissect their potential characteristic from three levels:
      sequence, secondary structure and transcriptional regulation. As a result,
      functional synergetic miRNA pairs exhibit high seed sequence and secondary
      structure similarity, and these characteristics are significant even when
      analyzing synergism between miRNAs from different families. Additionally,
      synergistic miRNAs tend to share a common transcriptional regulatory mechanism. A
      striking property of miRNAs with both synergism and co-regulation is their
      central roles in the MFSN, and tends to be involved in complex diseases. The
      potential characteristic in these three levels are validated to be robust by
      analyzing different MFSNs. Finally, we identified four tightly cooperative miRNA
      sub-networks which are also co-regulated by transcription factors, all of which
      regulate many important functions, including embryonic development, oncogenesis
      and micromanagement of metastasis, helping us to further understand the
      "language" of transcriptional and post-transcriptional regulation from a cross
      layer view.

PMID- 23154825
TI  - Lumican regulates ventilation-induced epithelial-mesenchymal transition through
      extracelluar signal-regulated kinase pathway.
AB  - BACKGROUND: Mechanical ventilation used in patients with acute lung injury can
      damage pulmonary epithelial cells through production of inflammatory cytokines
      and excess deposition of the extracellular matrix protein lumican. Lumican
      participates in macrophage inflammatory protein (MIP)-2 and transforming growth
      factor-beta1 (TGF-beta1) signaling during the fibroproliferative phase of acute
      lung injury, which involves a process of epithelial-mesenchymal transition (EMT).
      The mechanisms regulating interactions between mechanical ventilation and lung
      injury are unclear. We hypothesized that lung damage and EMT by high tidal volume
      (Vt) mechanical stretch causes upregulation of lumican that modulates MIP-2 and
      TGF-beta1 through the extracellular signal-regulated kinase (ERK) 1/2 pathway.
      METHODS: Male C57BL/6 mice (either wild type or lumican null) aged 3 months and
      weighing between 25 and 30 g were exposed to low Vt (6 mL/kg) or high Vt (30
      mL/kg) mechanical ventilation with room air for 2 to 8 h. Nonventilated mice were
      used as control subjects. RESULTS: We found that high Vt mechanical ventilation
      increased microvascular permeability, neutrophil influx, production of free
      radicals, MIP-2 and TGF-beta1 proteins, positive staining of alpha-smooth muscle
      actin and S100A4/fibroblast-specific protein-1, Masson trichrome staining and
      extracellular collagen, and activation of lumican and ERK1/2 in wild-type mice.
      Decreased staining of the epithelial marker E-cadherin was also observed.
      Mechanical stretch-augmented EMT was attenuated with lumican-deficient mice and
      pharmacologic inhibition of ERK1/2 activity by PD98059. CONCLUSIONS: The data
      suggest that lumican promotes high Vt mechanical ventilation-induced lung injury
      and EMT through the activation of the ERK1/2 pathway.

PMID- 23154829
TI  - AN AUTOMATIC FEATURE BASED MODEL FOR CELL SEGMENTATION FROM CONFOCAL MICROSCOPY
      VOLUMES.
AB  - We present a model for the automated segmentation of cells from confocal
      microscopy volumes of biological samples. The segmentation task for these images
      is exceptionally challenging due to weak boundaries and varying intensity during
      the imaging process. To tackle this, a two step pruning process based on the Fast
      Marching Method is first applied to obtain an over-segmented image. This is
      followed by a merging step based on an effective feature representation. The
      algorithm is applied on two different datasets: one from the ascidian Ciona and
      the other from the plant Arabidopsis. The presented 3D segmentation algorithm
      shows promising results on these datasets.

PMID- 23154830
TI  - NIR light controlled photorelease of siRNA and its targeted intracellular
      delivery based on upconversion nanoparticles.
AB  - The most notable role of small interfering RNA (siRNA) is in RNA interference
      (RNAi) and post-transcriptional gene silencing, which leads to a surge of
      interest in RNAi for both biomedical research and therapeutic applications.
      However, "naked" siRNA cannot cross cellular membranes freely because of highly
      negative charges which limits its utility for gene therapy. In this work, a
      system of near-infrared (NIR) light-induced siRNA release from silica coated
      upconversion nanoparticles (Si-UCNPs) is presented. These Si-UCNPs were
      functionalized with cationic photocaged linkers through covalent bonding, which
      could effectively adsorb anionic siRNA through electrostatic attractions and were
      easily internalized by living cells. Upon NIR light irradiation, the photocaged
      linker on the Si-UCNPs surface could be cleaved by the upconverted UV light and
      thus initiated the intracellular release of the siRNA. The in vitro agarose gel
      electrophoresis and intracellular imaging results indicated that the Si-UCNPs
      based gene carrier system allowed effective siRNA delivery and the applications
      of NIR light instead of direct high energy UV irradiation may greatly guarantee
      less cell damage.

PMID- 23154832
TI  - Myositis ossificans circumscripta of the triceps muscle in a Rottweiler dog.
AB  - A 20-month-old male Rottweiler dog was presented with the complaint of chronic
      right forelimb lameness that was unresponsive to conservative treatment. Physical
      examination allowed for the topographical identification of the source of the
      problem as a firm enlargement of the soft tissues that was partially movable from
      humeral bone and compatible with an alteration of the triceps brachii muscle.
      Radiographic images showed signs that were highly suggestive of myositis
      ossificans. Computed tomography allowed for a more accurate characterization of
      the lesion, to exclude involvement of the elbow joint and humeral bone, and to
      localize anatomically the lesion in the caput accessorium and longum of the
      triceps brachii muscle. Surgical excision of the ossified portion of the triceps
      muscle was performed. Histological examination of the excised tissue
      substantiated the diagnosis of myositis ossificans. A one year clinical and
      radiographic follow-up examination showed a complete recovery, with no evidence
      of complications or recurrence. Despite myositis ossificans in dogs having
      previously been identified in the hindlimbs, this case of myositis ossificans
      circumscripta of the triceps muscle suggests that it may also occur in the
      muscles of the forelimb.

PMID- 23154831
TI  - Acquired hypermethylation of the P16INK4A promoter in abdominal paraganglioma:
      relation to adverse tumor phenotype and predisposing mutation.
AB  - Recurrent alterations in promoter methylation of tumor suppressor genes (TSGs)
      and LINE1 (L1RE1) repeat elements were previously reported in pheochromocytoma
      and abdominal paraganglioma. This study was undertaken to explore CpG methylation
      abnormalities in an extended tumor panel and assess possible relationships
      between metastatic disease and mutation status. CpG methylation was quantified by
      bisulfite pyrosequencing for selected TSG promoters and LINE1 repeats.
      Methylation indices above normal reference were observed for DCR2 (TNFRSF10D),
      CDH1, P16 (CDKN2A), RARB, and RASSF1A. Z-scores for overall TSG, and individual
      TSG methylation levels, but not LINE1, were significantly correlated with
      metastatic disease, paraganglioma, disease predisposition, or outcome. Most
      strikingly, P16 hypermethylation was strongly associated with SDHB mutation as
      opposed to RET/MEN2, VHL/VHL, or NF1-related disease. Parallel analyses of
      constitutional, tumor, and metastasis DNA implicate an order of events where
      constitutional SDHB mutations are followed by TSG hypermethylation and 1p loss in
      primary tumors, later transferred to metastatic tissue. In the combined material,
      P16 hypermethylation was prevalent in SDHB-mutated samples and was associated
      with short disease-related survival. The findings verify the previously reported
      importance of P16 and other TSG hypermethylation in an independent tumor series.
      Furthermore, a constitutional SDHB mutation is proposed to predispose for an
      epigenetic tumor phenotype occurring before the emanation of clinically
      recognized malignancy.

PMID- 23154833
TI  - Surviving the macrophage: tools and tricks employed by Mycobacterium
      tuberculosis.
AB  - Mycobacterium tuberculosis has evolved to withstand one of the most inhospitable
      cells within the human body, namely the macrophage, a cell that is normally
      geared toward the destruction of any invading microbe. How M. tuberculosis
      achieves this is still incompletely understood; however, a number of mechanisms
      are now known that provide advantages to M. tuberculosis for its survival and
      proliferation inside the macrophage. While some of these mechanisms are mediated
      by factors released by M. tuberculosis, others rely on host components that are
      being hijacked to benefit survival of M. tuberculosis within the macrophage as
      well to avoid the generation of an effective immune response. Here, we describe
      several of these mechanisms, also pointing out the potential usage of this
      knowledge toward the development of novel strategies to treat tuberculosis.
      Furthermore, we attempt to put the 'macrophage niche' into context with other
      intracellular pathogens and discuss some of the generalities as well as
      specializations that M. tuberculosis employs to survive. 

PMID- 23154834
TI  - Patient and facility characteristics associated with benzodiazepine prescribing
      for veterans with PTSD.
AB  - OBJECTIVE: Practice guidelines used in the Veterans Health Administration (VHA)
      caution against benzodiazepine use by veterans with posttraumatic stress disorder
      (PTSD) because of inefficacy and safety concerns. Although use has declined, the
      VHA prescription rate is >=30% nationally. To inform intervention design, this
      study examined patient- and facility-level correlates of benzodiazepine
      prescribing. METHODS: This cross-sectional study used 2009 national
      administrative VHA data to identify veterans with PTSD, benzodiazepine
      prescriptions, and various patient and facility characteristics. Correlates of
      benzodiazepine prescribing were determined with multivariable hierarchical logit
      models. RESULTS: Among 137 VHA facilities, 495,309 veterans with PTSD were
      identified, and 150,571 (30.4%) received a benzodiazepine prescription. Patient
      characteristics independently associated with benzodiazepine use included female
      gender, age >=30 years, rural residence, service-connected disability >=50%,
      Vietnam-era service, duration of PTSD diagnosis, and a comorbid anxiety disorder.
      However, case-mix adjustment for these variables accounted for <1% of prescribing
      variation. Facility characteristics independently associated with higher use
      included lower PTSD visit volume, higher rates of duplicate prescribing
      (concurrent use of more than one drug from a class), and lower rates of trazodone
      prescribing. These findings were corroborated in replication analyses.
      CONCLUSION: The ultimate goal is to ensure consistent access to guideline
      concordant PTSD treatment across the VHA. This study furthered this objective by
      identifying characteristics associated with benzodiazepine prescribing. Findings
      suggest that interventions could be designed to target individual high-volume
      prescribers or influence prescribing culture at the facility level.

PMID- 23154835
TI  - Risk for adjacent segment and same segment reoperation after surgery for lumbar
      stenosis: a subgroup analysis of the Spine Patient Outcomes Research Trial
      (SPORT).
AB  - STUDY DESIGN: Subgroup analysis of a prospective, randomized database. SUMMARY OF
      BACKGROUND DATA: Reoperation due to recurrence of index level pathology or
      adjacent segment disease is a common clinical problem. Despite multiple studies
      on the incidence of reoperation, there have been few comparative studies
      establishing risk factors for reoperation after spinal stenosis surgery. The
      hypothesis of this subgroup analysis was that lumbar fusion or particular patient
      characteristics, such as obesity, would render patients with lumbar stenosis more
      susceptible to reoperation at the index or adjacent levels. METHODS: The study
      population combined the randomized and observational cohorts enrolled in Spine
      Patient Outcomes Research Trial for treatment of spinal stenosis. The surgically
      treated patients were stratified according to those who had reoperation (n = 54)
      or no reoperation (n = 359). Outcome measures were assessed at baseline, 1 year,
      2 years, 3 years, and 4 years. The difference in improvement between those who
      had reoperation and those who did not was determined at each follow-up period.
      RESULTS: Of the 413 patients who underwent surgical treatment of spinal stenosis,
      54 (13%) underwent a reoperation within 4 years. At baseline, there were no
      significant differences in demographic characteristics or clinical outcome scores
      between reoperation and nonreoperation groups. Furthermore, between groups there
      were no differences in the severity of symptoms, obesity, physical examination
      signs, levels of stenosis, location of stenosis, stenosis severity, levels of
      fusion, levels of laminectomy, levels decompressed, operation time, and
      intraoperative or postoperative complications. There was an increased percentage
      of patients with duration of symptoms greater than 12 months in the reoperation
      group (56% reoperation vs. 36% no reoperation, P < 0.008). At final follow-up,
      there was significantly less improvement in the outcome of the reoperation group
      in MOS 36-item Short-Form Health Survey physical function (14.4 vs. 22.6, P <
      0.05), Oswestry Disability Index (-12.4 vs. -21.1, P < 0.01), and Sciatica
      Bothersomeness Index (-5 vs. -8.1, P < 0.006). CONCLUSION: Lumbar fusion and
      instrumentation were not associated with increased rate of reoperation at index
      or adjacent levels compared with nonfusion techniques. The only specific risk
      factor for reoperation after treatment of spinal stenosis was duration of
      pretreatment symptoms more than 12 months. The overall incidence of reoperations
      for spinal stenosis surgery was 13%, and reoperations were equally distributed
      between index and adjacent lumbar levels. Reoperation may be related to the
      natural history of spinal degenerative disease.

PMID- 23154836
TI  - Evidence for juvenile disc herniation in a homo erectus boy skeleton.
AB  - STUDY DESIGN: An analysis and differential diagnosis of bony alterations in the
      lower lumbar vertebrae of a Homo erectus boy skeleton. OBJECTIVE: To analyze low
      back problems during early human evolution. SUMMARY OF BACKGROUND DATA: Back
      problems in modern humans are often attributed to our upright, bipedal locomotion
      that is thought to place huge mechanical stresses on the vertebral column.
      However, little is known of this situation during the course of human evolution.
      METHODS: We analyzed the lower lumbar spine of the most complete early hominid
      skeleton, the 1.5-million-year-old Homo erectus boy KNM-WT 15000 from
      Nariokotome, Kenya, who died at an age of approximately 8 years. We use bony
      alterations as indirect evidence for disc disease in the absence of soft tissue.
      RESULTS: We describe an extensive osteophytic anterior curved remodeling of the
      left superior articular process of L5 and formation of a new joint at the
      underside of the left pedicle of L4. This indicates collisional facet joint
      subluxation, most likely as the result of juvenile traumatic disc herniation.
      CONCLUSIONS: This indirect evidence of possible juvenile disc herniation in a
      Homo erectus boy skeleton represents the earliest known case of this typical
      human ailment that is intricately linked to upright bipedalism. The extensive
      bony remodeling of the articular processes of L4 and L5 suggests that the disc
      herniation occurred several months before his death. Disabling backache and
      recurrent sciatica might have, at least, temporarily restricted his daily
      activities, which indicates advanced social care and nursing in early Homo. We
      hypothesize that the early Homo intervertebral discs were more vulnerable to
      injury compared with modern humans because of a relatively small vertebral cross
      sectional area.

PMID- 23154837
TI  - Highly monodisperse rattle-structured nanomaterials with gold nanorod core
      mesoporous silica shell as drug delivery vehicles and nanoreactors.
AB  - Rattle-structured nanomaterials composed of a gold nanorod in a mesoporous silica
      nanocapsule (AuNR@mSiO(2)) were prepared by a novel solution-based consecutive
      process. The drug-loading properties of the nanomaterial and regrowth control of
      the core nanoparticles were also studied.

PMID- 23154838
TI  - Transduction of pressure signal to electrical signal upon sudden increase in
      turgor pressure in Chara corallina.
AB  - By taking advantage of large cell size of Chara corallina, we analyzed the
      membrane depolarization induced by decreased turgor pressure (Shimmen in J Plant
      Res 124:639-644, 2011). In the present study, the response to increased turgor
      pressure was analyzed. When internodes were incubated in media containing 200 mM
      dimethyl sulfoxide, their intracellular osmolality gradually increased and
      reached a steady level after about 3 h. Upon removal of dimethyl sulfoxide,
      turgor pressure quickly increased. In response to the increase in turgor
      pressure, the internodes generated a transient membrane depolarization at its
      nodal end. The refractory period was very long and it took about 2 h for full
      recovery after the depolarizing response. Involvement of protein synthesis in
      recovery from refractoriness was suggested, based on experiments using
      inhibitors.

PMID- 23154839
TI  - Unusual 9,19 : 24,32-dicyclotetracyclic triterpenoids from Lygodium japonicum.
AB  - Lygodipenoids A (1) and B (2), two novel C33 tetracyclic triterpenoids with a new
      9,19 : 24,32-dicyclopropane skeleton, were isolated from the whole grass of
      Lygodium japonicum. Their structures were elucidated by spectroscopic and
      chemical means. Compounds 1 and 2 were tested in transfected cultured human
      embryonic kidney 293 HEK293 cells for an agonist assay, and compound 1 was
      identified as a partial agonist for liver X receptor alpha.

PMID- 23154840
TI  - Phytochemical analysis and cytotoxicity towards multidrug-resistant leukemia
      cells of essential oils derived from Lebanese medicinal plants.
AB  - Juniperus excelsa fruit essential oil as well as J. oxycedrus, Cedrus libani, and
      Pinus pinea wood essential oils have been obtained with yields between 2.2 +/-
      0.3 % to 3.4 +/- 0.5 % and analyzed by gas chromatography. Sesquiterpenes mainly
      characterized C. libani and J. oxycedrus essential oils, while in P. pinea and J.
      excelsa, monoterpenes were the most abundant compounds. In J. oxycedrus, cis
      calamenene (7.8 %), cuparene (3.8 %), and cis-thujopsenal (2.0 %) have been
      detected for the first time. The cytotoxic activity of these essential oils
      against drug-sensitive CCRF-CEM and multidrug-resistant P-glycoprotein-expressing
      CEM/ADR5000 leukemia cells has been investigated (IC50 values: 29.46 to 61.54
      ug/mL). Remarkably, multidrug-resistant CEM/ADR5000 cells did not reveal cross
      resistance, indicating that these essential oils might be useful to treat
      otherwise drug-resistant and refractory tumors.

PMID- 23154841
TI  - Neuroprotective compounds from Salix pseudo-lasiogyne twigs and their anti
      amnesic effects on scopolamine-induced memory deficit in mice.
AB  - Bioassay-guided fractionation of an 80% methanolic extract of Salix pseudo
      lasiogyne twigs has resulted in the isolation of two new compounds (1-2) along
      with ten known ones (3-12). The new compounds were determined to be 3'-O
      acetylsalicin (1) and 2',6'-O-acetylsalicortin (2) by using spectroscopic
      analyses. Compounds (3-12) were identified as salicin (3), 2'-O-acetylsalicin
      (4), salicortin (5), 2'-O-acetylsalicortin (6), 3'-O-acetylsalicortin (7), 6'-O
      acetylsalicortin (8), 2'-O-(E)-rho-coumaroylsalicortin (9), grandidentatin (10),
      isograndidentatin (11), and saligenin (12). Among the isolated compounds,
      compounds 2, 5, 6, 7, and 8 bearing 1-hydroxy-6-oxo-2-cyclohexenecarboxylate
      moiety significantly inhibited lipopolysaccharide-induced nitric oxide production
      in BV2 microglial cells in vitro. Further, we studied anti-amnesic activities of
      the 80% methanolic extract, the EtOAc fraction, and compound 6 from S. pseudo
      lasiogyne. They exerted a significant cognitive-enhancing effect on scopolamine
      induced memory deficit in mice. In addition, they also significantly increased
      the reduced activities of glutathione reductase and superoxide dismutase and the
      glutathione content in the hippocampus and cortex of scopolamine-induced amnesic
      mice.

PMID- 23154843
TI  - Phenylpropanoid-substituted procyanidins and tentatively identified procyanidin
      glycosides from hawthorn (Crataegus spp.).
AB  - The rational use of hawthorn leafs and flowers from Crataegus spp. for declining
      cardiac performance is mainly due to flavon-C-glycosides and oligomeric
      procyanidins (OPC). From OPC-enriched extracts from different batches, a dimeric
      phenylpropanoid-substituted procyanidin (cinchonain II b, 1) was isolated and
      characterized by MS, CD, and NMR. Also the presence of higher oligomeric
      cinchonains (degree of polymerization 3 to 8) in hawthorn extracts was shown by a
      specific ultrahigh-pressure liquid chromatography-ESI-qTOF-MS method.
      Interestingly, strong evidence for the occurrence of oligomeric procyanidin
      hexosides was found by ultrahigh-pressure liquid chromatography-ESI-qTOF-MS
      analysis which additionally revealed the presence of peaks indicative of dimeric
      procyanidin hexosides by their exact mass, which were clearly distinguishable
      from the cinchonain II type peaks.

PMID- 23154842
TI  - Suppression of melanin synthesis by the phenolic constituents of sappanwood
      (Caesalpinia sappan).
AB  - Sappanwood (Caesalpinia sappan Linn.) is used as an herbal medicine. It is
      sometimes used to treat skin damage or as a facial cleanser. In the present
      study, the methanol (MeOH) extract of sappanwood was found to inhibit melanin
      synthesis in cultured human melanoma HMV-II cells stimulated with forskolin, and
      six active compounds (1-5 and 7) were isolated from the extract along with a non
      active compound (6). Compounds 2-7 were identified as sappanchalcone (2), 3'
      deoxy-4-O-methylsappanol (3), brazilein, (4), brazilin (5), sappanol (6), and 4-O
      methylsappanol (7). Compound 1 was a new compound, and its structure was
      determined to be (6aS,11bR)-7,11b-dihydro-6H-indeno[2,1-c]chromene-3,6a,10,11
      tetrol by spectroscopic analyses. Among the six active compounds, brazilin (5)
      (EC50: 3.0 +/- 0.5 uM) and 4-O-methylsappanol (7) (EC50: 4.6 +/- 0.7 uM) strongly
      suppressed melanin synthesis in HMV-II cells. Bioactive compounds showed moderate
      cytotoxicities against HMV-II cells with IC50 values of 83.1 +/- 4.0 uM (for 2),
      72.0 uM +/- 2.4 (for 3), 33.8 +/- 1.1 uM (for 4), 18.4 +/- 0.8 uM (for 5), and
      20.2 +/- 0.8 (for 7), respectively. Brazilin (5) selectively suppressed the
      expression of mRNAs for tyrosinase-related protein (TYRP) 2 and tyrosinase but
      did not influence the expression of TYRP1. These results suggest that brazilin
      (5) is a new class of melanin inhibitor and that sappanwood could be used as a
      cosmetic material.

PMID- 23154844
TI  - Validation of a novel algorithm for quantification of the percentage of signal
      fractionation in atrial fibrillation.
AB  - AIMS: Catheter ablation for paroxysmal atrial fibrillation (AF) is rapidly
      becoming a standard practice. There is literature to support that catheter
      ablation of persistent AF requires additional 'substrate modification'. In
      clinical practice, operators rely on automated fractionation maps created by
      three-dimensional anatomic mapping systems to rapidly assess complex
      'fractionated' signals (CFAE). These systems use differing algorithms to automate
      the process. The agreement between operators and contemporary algorithms has not
      been examined. We sought to assess the agreement between operators and a novel
      method of quantification calculating percentage fractionation (PF). METHODS AND
      RESULTS: Expert opinion on 80 atrial electrogram 4 s signals of varying levels of
      activity were gathered and pooled for comparison. Twelve independent experts
      visually quantified the signal fractionation and offered a threshold level for
      ablation. We developed an algorithm to find sites with high continuous electrical
      activity, or high PF. Correlation between experts and PF was 0.78 [P < 0.01, 95%
      confidence interval (CI) (0.68-0.86)]. Receiver operating characteristics curve
      sensitivity and specificity for PF were 0.7727 and 0.8103 at the optimal cut-off
      point of 58.45 PF with area under curve 0.89 CI (0.80-0.99). CONCLUSION: The PF
      statistic represents a more robust and intuitive measure to represent
      fractionated atrial activity; importantly it demonstrates excellent agreement
      with expert users and presents a new standard for algorithm assessment. Use of a
      PF statistic should be considered in automated mapping systems.

PMID- 23154845
TI  - [Imaging strategies for knee injuries].
AB  - Injuries of the knees are common. The Ottawa knee rule provides decisional
      support to determine whether radiographs are indicated or not. With the use of
      ultrasound it is possible to detect defects of the extensor ligaments and the
      anterior cruciate ligament. Furthermore, it is possible to detect indirect signs
      of an intra-articular fracture, e.g. lipohemarthrosis. In complex fractures, e.g.
      tibial plateau fractures, further diagnostic procedures with multislice computed
      tomography (CT) are needed for accurate classification and preoperative planning.
      Multislice CT with CT angiography enables three-dimensional reconstruction of the
      knee and non-invasive vascular imaging for detection of vascular injury. Magnetic
      resonance imaging (MRI) is the gold standard for detection of occult fractures
      and injuries of the ligaments and menisci. Higher field strengths can be used to
      improve the diagnostics of cartilage lesions. Virtual MR arthrography is superior
      to conventional MRI for detection of cartilage lesions especially after meniscus
      surgery.

PMID- 23154846
TI  - [Radiological findings, evaluation and treatment of patellofemoral pain after
      total knee arthroplasty].
AB  - Total knee arthroplasty (TKA) is one of the most successful operative procedures
      over the last decades in orthopedic surgery; however, some patients suffer from
      pain, limited range of motion, instability, infections or other complications
      postoperatively. Patellofemoral pain (PFP) in particular is a common problem
      after TKA and often necessitates revision surgery. Mainly increasing and
      localized contact pressure and patella maltracking are held responsible for PFP
      but the reasons vary. Diagnostics and therapy of PFP is not easy to manage and
      should be treated following a clinical pathway. The authors suggest that patients
      with PFP should be categorized after basic diagnostic measures according to the
      suspected diagnosis: (1) tendinosis, (2) mechanical reasons, (3) intra-articular
      non-mechanical reasons and (4) neurogenic/psychiatric reasons. Efficient
      application of special diagnostic measures and further therapy is facilitated by
      this classification.

PMID- 23154847
TI  - [Imaging of postarthroscopic complications after knee injuries].
AB  - The most common joint injuries in professional and recreational sports
      participants and also in the total population are knee injuries. Arthroscopy is
      indicated if this modality will improve the patient outcome and potential long
      term complications can be avoided. Although uncommon, complications following
      arthroscopy are mostly evaluated by magnetic resonance imaging (MRI). For
      planning further therapy strategies following postarthroscopic complications,
      e.g. if anterior cruciate ligament (ACL) reconstruction is required, digital
      radiographs and computed tomography (CT) are helpful. This article provides an
      overview of the different procedures for surgical treatment which are a
      prerequisite for the analysis of postarthroscopic images. In addition typical
      complications after treatment of meniscal and chondral injuries as well as after
      ACL reconstruction are described and typical signs in MRI, radiography and CT are
      explained in detail.

PMID- 23154848
TI  - [Femoral osteonecrosis - Ahlbaeck's disease].
AB  - Osteonecrosis of the knee can present as a spontaneous, primary (SPON) or a
      secondary clinical entity (SON). The natural history of SPON follows a course of
      several sequential stages which seem to be irreversible in later stages of both
      entities. Early diagnosis of ON is crucial and the earlier the stage of the
      lesion at the time of diagnosis, the better the prognosis. Clinically, early
      diagnosis and treatment of ON might prevent unnecessary surgery in cases with a
      concomitant degenerative meniscal tear. From a medicolegal viewpoint early-stage
      ON should be ruled out prior to surgery as arthroscopy has recently been
      associated with ON. Recent biopsy studies showed that SPONK is most likely caused
      by insufficiency fractures which seem to appear as osteonecrotic lesions in later
      stages of the disease due to failed bone healing.

PMID- 23154849
TI  - [Tumor-like diseases of the knee joint].
AB  - CLINICAL/METHODICAL ISSUE: Radiological diagnostics of tumor-like lesions of the
      knee joint. STANDARD RADIOLOGICAL METHODS: Magnetic resonance imaging (MRI),
      computed tomography (CT) and X-ray imaging. PERFORMANCE: Up to now there have
      been no studies regarding sensitivity and specificity of the various diagnostic
      tools (MRI, CT, X-ray) for the visualization of soft tissue tumors of the knee.
      PRACTICAL RECOMMENDATIONS: The method of first choice for detecting soft tissue
      tumors and tumor-like lesions in the knee joint is MRI.

PMID- 23154850
TI  - [Tumors and pseudotumors of the mediastinum].
AB  - Space occupying lesions of the mediastinum are relatively common. They represent
      a wide spectrum of diseases including highly malignant tumors requiring immediate
      further diagnostic and therapeutic procedures as well as clinically insignificant
      findings and normal variants. This review provides an overview of different
      mediastinal tumors and pseudotumors. Furthermore, it aims at enabling the reader
      to classify mediastinal lesions according to the pathogenesis and clinical
      significance. Localization of the lesion within a specific mediastinal
      compartment may suggest the etiology and thus the differential diagnosis. Also,
      morphological imaging criteria may suggest the diagnosis. The reader of this
      review should be able to reliably classify mediastinal lesions which exhibit
      these specific features without histological examination.

PMID- 23154852
TI  - A CURVICYLINDRICAL COORDINATE SYSTEM FOR THE VISUALIZATION AND SEGMENTATION OF
      THE ASCIDIAN TAIL.
AB  - State of the art biological imaging methods, such as confocal microscopy, create
      3D volumes by sampling on a cartesian grid. This cartesian coordinate system is
      often not convenient for visualization and analysis of multi layered organs or
      tissues. The ascidian embryonic tail, for example, is organized along
      anterioposterior (AP), dorsoventral (DV) and left-right (LR) axes that are
      locally orthogonal but curved in the XYZ microscope space. Here, we propose a
      "curvicylindrical" coordinate system for analysis of such biological structures.
      By extracting representative paths that traverse different tissue layers, the
      embryo can be visualized in a small number of 2D images (3 images in the case of
      the ascidian tail). As we demonstrate, this reduction of the dimensionality from
      3D to 2D facilitates the initialization process for high quality segmentation of
      different cell types, and identification of tissue boundaries.

PMID- 23154853
TI  - Unravelling homeostatic interactions in inhibitory and excitatory networks in
      human motor cortex.

PMID- 23154854
TI  - Of apples and oranges: GABA and glutamate transmission in neurones of the nucleus
      tractus solitarii could not be more different.

PMID- 23154855
TI  - The elusive roles of NMDA receptor amino-terminal domains.

PMID- 23154856
TI  - [Stage diving - a dangerous "sport"].

PMID- 23154857
TI  - An endovascular technique for treatment of high-risk iatrogenic aortic
      pseudoaneurysms with the ethylene vinyl alcohol copolymer onyx and aortic stent
      grafting.

PMID- 23154858
TI  - [Intrapancreatic accessory spleen - an important differential diagnosis of
      primary pancreatic tail neoplasia].

PMID- 23154859
TI  - [Interventional treatment of splenic vein thrombosis and esophageal varices
      hemorrhage].

PMID- 23154860
TI  - [A rare but serious radiological diagnosis view - emphysematous pyelonephritis].

PMID- 23154861
TI  - [Ipilimumab-induced hypophysitis].

PMID- 23154862
TI  - [Dose area product of pediatric VCUG with regard to the strongly lowered German
      diagnostic reference levels].
AB  - PURPOSE: To compare the dose area products of pediatric VCUG in daily practice
      with the dramatically reduced official German diagnostic reference levels, which
      are based on selected data. MATERIALS AND METHODS: 413 consecutive pediatric VCUG
      examinations were analyzed. RESULTS: The mean dose area product of all
      examinations was 0.97 dGycm2. This is below the lowest reference level that is
      valid for neonates. In 12 cases (5.6 %) the achieved dose area product was higher
      than the corresponding reference level. CONCLUSION: Using the available
      techniques for radiation protection, it is possible in the daily routine to meet
      the official diagnostic reference levels for children, which have been reduced by
      up to 80 %, even though these levels are based on a selected, possibly non
      representative data set.

PMID- 23154863
TI  - Dual nucleophilic/electrophilic capture of in situ generated iminium ethers:
      towards the synthesis of functionalized amide building blocks.
AB  - Rearranging its feathers: The transformation of simple linear amides into a
      diverse range of branched, functionalized products by conversion to iminium
      esters is followed by sequential treatment with nucleophiles and electrophiles
      (see scheme). The method takes advantage of a novel Claisen rearrangement and the
      use of aromatic substrates greatly facilitates the formation of the intermediate
      iminium ether.

PMID- 23154864
TI  - Quality of life of oropharyngeal cancer patients with respect to treatment
      strategy and p16-positivity.
AB  - OBJECTIVES/HYPOTHESIS: To assess the quality of life in long-term survivors with
      oropharyngeal cancer (OPSCC), compare the results with our historic cohort in
      relation to the radiation technique, and explore the influence of treatment
      strategy and p16 expression on quality of life (QoL). STUDY DESIGN: Retrospective
      chart analysis and patient response to EORTC QLQ-C30 and EORTC QLQ-H&N35 survey
      questionnaires. METHODS: 98/120 (82%) survivors treated by primary intensity
      modulated chemoradiation (n = 55), or surgery with (n = 30) or without (n = 13)
      adjuvant radiotherapy (RT), completed and returned the questionnaires. RESULTS:
      Surgically treated patients complained about significantly less troubles with dry
      mouth and teeth compared to the nonsurgically treated group. Comparing patients
      treated with surgery alone and those receiving any kind of RT (primary or
      adjuvant) the latter group complained about significantly more problems. Patients
      with p16-positive tumors demonstrated significantly higher tumor stages, but
      significantly better scores in physical and role functions. CONCLUSIONS: Early
      disease can be treated with high long-term QoL by surgery alone. Primary surgery
      with postoperative RT in selected patients with limited primary tumors and
      advanced neck disease renders excellent QoL. Our results suggest that IMRT is
      superior to former radiation techniques with regard to QoL, and should be
      considered as standard of care in patients undergoing RT for OPSCC. Patients with
      p16 positive tumors appear to show not only a better outcome but also report on a
      better QoL.

PMID- 23154865
TI  - Enhanced heterodimerization of Bax by Bcl-2 mutants improves irradiated cell
      survival.
AB  - B Cell Lymphoma-2 (Bcl-2) protein suppresses ionizing radiation-induced apoptosis
      in hemato-lymphoid system. To enhance the survival of irradiated cells, we have
      compared the effects and mechanism of Bcl-2 and its functional variants, D34A
      (caspase-3 resistant) and S70E (mimics phosphorylation on S70). Bcl-2 and its
      mutants were transfected into hematopoietic cell line and assessed for cell
      survival, clonogenicity and cell cycle perturbations upon exposure to ionizing
      radiation. The electrostatic potential of BH3 cleft of Bcl-2/mutants and their
      heterodimerization with Bcl-2 associated X protein (Bax) were computationally
      evaluated. Correspondingly, these results were verified by co-immunoprecipitation
      and western blotting. The mutants afford higher radioprotective effect than Bcl-2
      in apoptotic and clonogenic assays at D(0) (radiation dose at which 37 % cell
      survival was observed). The computational and functional analysis indicates that
      mutants have higher propensity to neutralize Bax protein by heterodimerization
      and have increased caspase-9 suppression capability, which is responsible for
      enhanced survival. This study implies potential of Bcl-2 mutants or their
      chemical/peptide mimics to elicit radioprotective effect in cells exposed to
      radiation.

PMID- 23154866
TI  - Molecular basis of primary iron overload in India and the role of serum-derived
      factors in hepcidin regulation.

PMID- 23154867
TI  - Relapse of aHUS after discontinuation of therapy with eculizumab in a patient
      with aHUS and factor H mutation.

PMID- 23154868
TI  - Prenatal diagnosis of ambient cistern cyst.

PMID- 23154869
TI  - Strain assessment in surgically resected inflammatory and neoplastic bowel
      lesions.
AB  - PURPOSE: To investigate whether ultrasound-based strain imaging can discriminate
      between colorectal adenocarcinomas and stenotic Crohn's lesions in newly resected
      surgical specimens. MATERIALS AND METHODS: Resected surgical specimens from 27
      patients electively operated for colorectal tumors or stenotic lesions from
      Crohn's disease were prospectively examined with ultrasonography using a Hitachi
      HV 900 US scanner with real-time elastography (RTE). Three different methods were
      applied to assess tissue strain: A four-level categorical visual classification,
      a continuous visual analog scale (VAS, 0 - 100) and a strain ratio (SR)
      measurement between the lesion and surrounding reference tissue. The imaged
      sections were marked and subsequently examined by a pathologist. Results from RTE
      were evaluated according to diagnosis, degree of fibrosis, inflammatory
      parameters, tumor stage and grade. RESULTS: 16 sections from Crohn's lesions, 18
      sections from adenocarcinomas and 4 sections from adenomas were examined. Both
      adenocarcinomas and Crohn's lesions were found to be harder than the surrounding
      tissue, but they could not be discriminated from each other by any of the strain
      imaging evaluation methods. All adenocarcinomas had significantly higher strain
      ratios than adenomas. The categorical classification differentiated poorly
      between Crohn's lesions, adenocarcinomas and adenomas. Categorical evaluation and
      VAS score showed fair interobserver agreement. SR measurements provided semi
      quantitative strain data and added improved information about elasticity
      properties, despite substantial intra-observer variation. CONCLUSION:
      Sonoelastography with SR measurements and visual evaluation of strain differences
      could not differentiate stenotic Crohn's lesions from adenocarcinomas in resected
      bowel specimens. A small number of adenomas were found to be significantly softer
      than adenocarcinomas using the same evaluation methods. The tumor stage or grade
      did not have a significant impact on the elastography results.

PMID- 23154870
TI  - Imaging features of intrahepatic biliary cystadenoma and cystadenocarcinoma on B
      mode and contrast-enhanced ultrasound.
AB  - PURPOSE: To investigate the imaging features of intrahepatic biliary cystadenoma
      and cystadenocarcinoma on B-mode and contrast-enhanced ultrasound. MATERIALS AND
      METHODS: The B-mode and contrast-enhanced ultrasound features of 6 intrahepatic
      biliary cystadenomas and 7 intrahepatic biliary cystadenocarcinomas were
      retrospectively analyzed, and the differences between cystadenomas and
      cystadenocarcinomas were compared. RESULTS: There were no significant differences
      between cystadenomas and cystadenocarcinomas in terms of patient gender, age,
      lesion location, size, and shape (all p > 0.05). On conventional ultrasound,
      biliary cystadenomas were more likely to be multilocular (6/6 for cystadenoma vs.
      2/7 for cystadenocarcinoma) and cystadenocarcinomas more likely presented the
      features of a mural or septal nodule and a nodule diameter > 1.0 cm (0/6 for
      cystadenoma vs. 5/7 for cystadenocarcinoma). On contrast-enhanced ultrasound,
      hyper-enhancement (n = 4) or iso-enhancement (n = 2) was present in the cystic
      wall, septations or mural nodules of the cystadenomas during the arterial phase
      and the enhancement washed out to hypo-enhancement (n = 6) during the late phase.
      Cystadenocarcinomas also showed hyper-enhancement (n = 4) or iso-enhancement (n =
      3) in the cystic wall, septations or mural nodules during the arterial phase and
      iso-enhancement (n = 1) or hypo-enhancement (n = 6) during the late phase.
      CONCLUSION: Intrahepatic biliary cystadenomas are more typically multilocular
      cystic lesions. A mural or septal nodule and a nodule diameter greater than 1.0
      cm on conventional ultrasound are suggestive of cystadenocarcinomas. Contrast
      enhanced ultrasound is helpful for depicting the vascularity of the lesions but
      there was no significant difference between cystadenomas and cystadenocarcinomas.

PMID- 23154871
TI  - Dynamic contrast-enhanced ultrasound (DCE-US) for easy and rapid evaluation of
      hepatocellular carcinoma compared to dynamic contrast-enhanced computed
      tomography (DCE-CT)--a pilot study.
AB  - PURPOSE: To check the feasibility of the easy quantification of tumor
      vascularization derived from dynamic contrast-enhanced ultrasound (DCE-US) in
      comparison to dynamic contrast-enhanced computed tomography (DCE-CT) in patients
      with hepatocellular carcinoma (HCC). MATERIALS AND METHODS: 19 patients with
      cirrhosis and histologically proven HCC prospectively underwent CEUS (SonoVue)
      and CT (Imeron400). Following CEUS, the software ImageJ was used for the easy
      quantification of the echogenicity in HCC lesions and tumor-free liver
      parenchyma. For DCE-CT we used the software Hepacare and created arterial
      enhancement fraction color maps of the whole liver and HCC lesions. RESULTS:
      Unifocal/multifocal HCCs were detected in 12/7 (US) and 10/9 patients (CT) and
      biopsied nodules were defined as a reference lesion with a median of 40 mm (US)
      and 42 mm (CT). CEUS showed HCC-typical hyper-/hypoenhancement in the
      arterial/late phase in 16/19 reference lesions, while all reference lesions
      showed an HCC-typical vascular pattern in CT. With DCE-US, quantitative
      assessment could not be performed in 3/19 patients due to respiratory motion or
      insufficient image quality. 13/16 reference lesions showed an HCC-typical
      vascular pattern. Quantitative assessment was possible with DCE-CT in all
      patients and all reference nodules showed HCC-typical values of the arterial
      enhancement fraction. There was no statistical difference between CEUS, DCE-US
      and DCE-CT in the quantitative assessment of contrast enhancement. CONCLUSION:
      The quantitative evaluation of DCE-US was feasible in HCC without a statistical
      difference with respect to DCE-CT. Further studies with a larger study population
      including small nodules <= 2 cm are needed to assess whether this technique is
      helpful in routine ultrasound.

PMID- 23154872
TI  - Protein surface and core dynamics show concerted hydration-dependent activation.
AB  - By specifically labeling leucine/valine methyl groups and lysine side chains
      "inside" and "outside" dynamics of proteins on the nanosecond timescale are
      compared using neutron scattering. Surprisingly, both groups display similar
      dynamics as a function of temperature, and the buried hydrophobic core is
      sensitive to hydration and undergoes a dynamical transition.

PMID- 23154873
TI  - Clinical impact of A/H1/N1/09 influenza in patients with cirrhosis: experience
      from a nosocomial cluster of infection.
AB  - A/H1N1/09 influenza is associated with a high risk of complications in patients
      with chronic diseases, but data on morbidity and mortality in patients with
      cirrhosis are limited. A cluster of A/H1N1/09 infection in 48 patients admitted
      to a Gastro-Hepatology Unit is reported. Nosocomial spread, clinical outcome, and
      viral characteristics of A/H1N1/09 strains from a study group of 48 inpatients
      (21 and 27 with and without cirrhosis, respectively) were compared with those
      from a control group of 44 outpatients with mild influenza-like illness and
      without cirrhosis. A/H1N1/09 infection was confirmed in 8/48 (17%) inpatients.
      A/H1N1/09 infection rate did not differ in patients with and without cirrhosis
      (4/21, 19%; 4/27, 15%), but three patients with cirrhosis died of pneumonia and
      acute respiratory distress syndrome, with fungal or bacterial superinfection in
      two cases, despite antiviral treatment. None of patients without cirrhosis died.
      Viral sequences showed the presence of hemagglutinin mutation D222G in two out of
      three fatal cases and S183P in seven out of eight infected patients. These
      mutants were not detected in the outpatients group. Even if A/H1N1/09 infection
      rate in hospitalized patients with and without cirrhosis was not significantly
      different, cirrhosis and D222G/S183P substitutions were significantly associated
      with severe disease and poor outcome, also suggesting fungal or bacterial
      superinfection and portal hypertension as risk factors for A/H1N1/09 disease
      severity in patients with cirrhosis. Vaccination, preventive and early treatment
      and a strict control of nosocomial spread should be activated carefully in
      patients with cirrhosis during epidemics influenza.

PMID- 23154874
TI  - Should lamivudine monotherapy be stopped or continued in patients infected with
      hepatitis B with favorable responses after more than 5 years of treatment?
AB  - Regarding the limited evidence for determining the optimal duration of antiviral
      treatment for hepatitis B, the long-term outcome of patients with favorable
      responses to over 5 years of lamivudine monotherapy was investigated. Two hundred
      seventy-one patients who had received lamivudine for at least 5 years were
      enrolled. Ultimately, 72 patients without YMDD mutations and showing hepatitis B
      virus (HBV) DNA levels <2.5 pg/ml after 5 years of treatment were analyzed. Mean
      treatment duration with lamivudine was 9.1 +/- 2.6 years. During the treatment,
      HBeAg and HBsAg loss/seroconversion rates were 95 and 6.9%, respectively.
      Decompensation and hepatocellular carcinoma (HCC) developed in 2.8 and 6.9% of
      patients, respectively. Old age and cirrhosis were risk factors for HCC
      development. Finally, 11.1% of patients developed YMDD mutations after 8.3 +/-
      2.4 years of treatment. There was no hepatic decompensation among the patients
      who developed delayed YMDD mutations. Sixteen patients who achieved a complete
      response stopped lamivudine and four patients showed relapses 10.3 +/- 8.5 months
      after stopping lamivudine. Relapsed patients had more cirrhotic livers and higher
      rates of HBeAg positivity at 5 years than patients who maintained complete
      response. The present study suggests that patients who do not develop YMDD
      mutations over 5 years of treatment with lamivudine may continue lamivudine
      monotherapy until the loss of HBsAg. However, even for the patients showing
      favorable response over 5 years of treatment, those in older ages, with cirrhosis
      or who show poor HBeAg responses should be on careful monitoring to detect the
      development of viral mutations, relapse and even HCC.

PMID- 23154875
TI  - Molecular analysis of hepatitis B virus in Bulgaria.
AB  - Hepatitis B virus infection is a global health problem. Based on the sequence
      divergence of the entire genome, hepatitis B virus has been classified into eight
      genotypes which have a characteristic geographic distribution. To date, no data
      are available on the molecular epidemiology of hepatitis B virus in Bulgaria. The
      aim of the present study was to reconstruct the epidemiological history of HBV
      genotypes/subgenotypes circulating in Bulgaria using a phylodynamic approach and
      a Bayesian statistical inference framework. Sequence analysis of the
      HBsAg/Reverse Transcriptase overlapping genomic regions revealed that D1 and A2
      were the subgenotypes detected most frequently in the patients examined. The
      tMRCA estimations of the few HBV D1 Bulgarian significant clades dated back to 23
      27 years ago, corresponding to the early 1980s. The HBV A2 Bulgarian sequences
      fell into two closely related supported clusters dated to 2003 and 1996 years,
      respectively, suggesting a more recent introduction of subgenotype A2 into
      Bulgaria. The study provides new information about the HBV subgenotypes in
      Bulgaria.

PMID- 23154876
TI  - Baseline factors and early viral response (week 4) to antiviral therapy with
      peginterferon and ribavirin for predicting sustained virologic response in
      patients infected with hepatitis C virus genotype 1: a multicenter study.
AB  - Both baseline predictive factors and viral response at week 4 of therapy are
      reported to have high predictive ability for sustained virologic response to
      peginterferon and ribavirin combination therapy in patients with hepatitis C
      virus (HCV) genotype 1. However, it is not clear how these baseline variables and
      week 4 response should be combined to predict sustained virologic response. In
      this multicenter study, the authors investigated the impact of baseline
      predictive factors on the predictive value of week 4 viral response. Receiver
      operating characteristic curve analyses were performed to evaluate the ability of
      week 4 reduction in HCV RNA levels to predict sustained virologic response in 293
      Japanese patients infected with HCV genotype 1b. Analyses were performed in all
      patients and in patient subgroups stratified according to baseline variables.
      Overall, week 4 viral reduction demonstrates a high predictive ability for
      sustained virologic response. The sensitivity, specificity, positive predictive
      value (PPV), negative predictive value, and accuracy were higher than those of
      viral reduction at week 12. However, the best cut-off levels differ depending on
      the baseline factors and they were lower in patients with unfavorable baseline
      predictors. When patients had the TG/GG rs8099917 genotype, the best cut-off was
      markedly low with low PPV. Week 4 viral response can be a predictor of sustained
      virologic response in patients with HCV genotype 1 and is better than week 12
      viral response. However, the cut-off levels should be modified based on the
      baseline predictive variables.

PMID- 23154877
TI  - Comparison of two commercial ELISA systems for evaluating anti-EBNA1 IgG titers.
AB  - High IgG titers against the Epstein-Barr virus nuclear antigen, EBNA-1, have been
      strongly correlated with the risk of developing multiple sclerosis. ELISAs are
      used frequently to measure EBNA-1 titers, however concerns remain regarding the
      accuracy of results. Ordering absolute results into rank quintiles for analysis
      may be preferable. Using 120 serum samples, two commercially available ELISAs
      (produced by DiaSorin and VirionSerion) were compared, both in terms of absolute
      results and rank quintiles. The positive predictive value of the VirionSerion
      ELISA was 99.1% when compared to the DiaSorin ELISA, however, the negative
      predictive value was 64.3%. Sensitivity and specificity were acceptable at 95.5%
      and 90.0%, respectively. There was poor correlation between absolute results,
      R(2)  = 0.49; and the kappa coefficient for rank quintiles was low at 0.23.
      Although sensitivity and specificity appear adequate, the poor negative
      predictive value and kappa coefficient are of major concern. Care must be taken
      when selecting assays for experimental use.

PMID- 23154878
TI  - Shedding of polyomavirus in the saliva of immunocompetent individuals.
AB  - The aim of this study was to investigate and compare the frequency of BKV, JCV,
      WUV, and KIV in the saliva of healthy individuals. Samples were analyzed for the
      presence of polyomaviruses (BKV, JCV, WUV, and KIV) DNA by real-time PCR. Of the
      291 samples tested, 71 (24.3%) were positive for at least one of the screened
      polyomaviruses. Specifically, 12.7% (37/291) were positive for WUV, 7.2% (21/291)
      positive for BKV, 2.4% (7/291) positive for KIV, and 0.3% (1/291) positive for
      JCV. BKV and WUV co-infections were detected in 1.7% (5/291) of individuals. No
      other co-infection combinations were found. The mean number of DNA copies was
      high, particularly for WUV and BKV, indicating active replication of these
      viruses. Polyomavirus detection was higher among individuals 15-19 years of age
      (46.0%; 23/50) and >=50 years of age (33.3%; 9/27). However, the detection rate
      in the first group was almost 1.7* greater than the latter. WUV infections were
      more frequent in individuals between the ages of 15 and 19 years and the
      incidence decreased with age. By contrast, BKV excretion peaked and persisted
      during the third decade of life and KIV infections were detected more commonly in
      subjects >=50 years old. These findings reinforced the previous hypotheses that
      saliva may be a route for BKV transmission, and that the oral cavity could be a
      site of virus replication. These data also demonstrated that JCV, WUV, and KIV
      may be transmitted in a similar fashion.

PMID- 23154879
TI  - Respiratory syncytial virus protects against the subsequent development of
      ovalbumin-induced allergic responses by inhibiting Th2-type gammadelta T cells.
AB  - Respiratory syncytial virus (RSV) infection has been hypothesized to be a risk
      factor for the development of allergy and asthma, but epidemiologic studies in
      humans still remain inconclusive. The association between RSV infection and
      allergic diseases may be dependent on an atopic background and previous history
      of RSV infection. It has been reported that RSV infection before sensitization to
      an allergen decreased the production of Th2-like cytokines in the lung and the
      levels of allergen-specific Th2-type antibodies in the serum. However, the
      underlying mechanisms are largely unknown. In the present study, the role of
      pulmonary gammadelta T cells in RSV-affected, allergen-induced airway
      inflammation was investigated. BALB/c mice were sensitized to or challenged with
      ovalbumin (OVA) and infected with RSV either before or after the sensitization
      period. It became clear that sensitization and challenge of mice with OVA induced
      a large influx of gammadelta T cells to the lungs. However, prior RSV infection
      inhibited the infiltration of gammadelta T cells as well as activated gammadelta
      T cells, characterized by expression of CD40L or CD69 molecular in the cell
      surface. Moreover, prior RSV infection elevated the type 1 cytokine gene
      expression but suppressed type 2 cytokine expression in the lung gammadelta T
      cells. Adoptive transfer of gammadelta T cells from OVA-sensitized and challenged
      mice increased airway inflammation, suggesting that gammadelta T cells may play a
      proinflammatory role in allergic responses. These results described here support
      the idea of an unknown gammadelta T cell-dependent mechanism in the regulation of
      RSV-affected, allergen-induced allergic airway responses.

PMID- 23154880
TI  - Molecular characterization of serotype G9 rotaviruses circulating in South Korea
      between 2005 and 2010.
AB  - A total of 18 rotavirus G9 strains in South Korea were collected during five
      rotavirus seasons between 2005 and 2010. The relationship between these strains
      was examined by analyzing the genetic variation of two major structural genes,
      VP7 and VP4. All the rotavirus isolates were of the G9P[8] genotype. The VP7
      phylogenetic analysis demonstrated that all of the G9 rotaviruses circulating in
      South Korea belonged to lineage IIId and were within three single clusters. The
      amino acid comparison of the antigenic regions of the VP7 gene suggests possible
      common progenitors of these strains. Phylogenetic analysis of P[8] VP4 genotypes
      indicated three lineages, P[8]-2, P[8]-3, and P[8]-4, with P[8]-3 being the most
      common. The results of this study provide information on the genetic relatedness
      of rotavirus G9 strains circulating in South Korea over recent years and can be
      utilized for the development of effective vaccines and the identification of
      reference strains for future efficacy studies.

PMID- 23154881
TI  - Inhibition of Tulane virus replication in vitro with RNA interference.
AB  - RNA interference (RNAi), a conserved mechanism triggered by small interfering RNA
      (siRNA), has been used for suppressing gene expression through RNA degradation.
      The replication of caliciviruses (CVs) with RNAi was studied using the Tulane
      virus (TV) as a model. Five siRNAs targeting the non-structural, the major (VP1)
      and minor (VP2) structural genes of the TV were developed and the viruses were
      quantified using quantitative real time PCR (qPCR) and tissue culture infective
      dose (TCID(50) ) assay. Treatment of the cells with siRNA 4 hr before viral
      inoculation significantly reduced viral titer by up to 2.6 logs and dramatically
      decreased viral RNA copy numbers and viral titers 48 hr post infection in four of
      the five siRNAs studied. The results were confirmed by Western blot, in which the
      major structural protein VP1 was markedly reduced in both the cells and the
      culture medium. Two small protein bands of the shell (S) and protruding (P)
      domains of the viral capsid protein were also detected in the cell lysates,
      although their role in viral replication remains unknown. Since the TV shares
      many biological properties with human noroviruses (NoVs), the successful
      demonstration of RNAi in TV replication would provide valuable information in
      control of acute gastroenteritis caused by human NoVs.

PMID- 23154882
TI  - Sorafenib inhibits in vitro osteoclastogenesis by down-modulating Mcl-1.
AB  - The effect of the multi-kinase inhibitor Sorafenib was investigated in an in
      vitro model of human osteoclastogenesis, represented by peripheral blood
      mononuclear cells (PBMCs) induced to differentiate into osteoclast-like cells in
      presence of receptor activator of nuclear factor kappa B ligand (RANKL) plus
      macrophage-colony stimulating factor (M-CSF). Sorafenib significantly inhibited
      osteoclastic formation at clinically achievable concentrations (1-3 MUM) and
      promoted autophagia with minimal induction of apoptosis. At the molecular levels,
      the M-CSF + RANKL combination increased the expression level of the Bcl-2 family
      member Mcl-1 protein, which is known to play a key role in the control of both
      cell survival and autophagia. The simultaneous treatment with Sorafenib
      significantly down-regulated endogenous Mcl-1 expression. Conversely, over
      expression of Mcl-1 in primary human macrophages significantly counteracted the
      anti-osteoclastic activity of Sorafenib, strongly suggesting that Mcl-1 down
      regulation played a major role in mediating the inhibitory activity of Sorafenib
      in cells of the osteoclastic lineage.

PMID- 23154884
TI  - Placental extract protects bone marrow-derived stem/progenitor cells against
      radiation injury through anti-inflammatory activity.
AB  - Placental extracts have been reported to have anti-oxidative and anti
      inflammatory activities. Because there is increasing evidence that ionizing
      radiation induces the release of reactive oxygen species (ROS) and inflammatory
      cytokines, we examined the protective effects of a placental extract against
      radiation injury. C57BL/6 mice were exposed to 1 Gy of gamma-ray radiation every
      day for 5 days, and placental extract (1 mg/day) was administrated orally soon
      after each exposure. At 2 days after the last irradiation, mice were euthanized
      to examine the numbers, colony-forming capacity, and DNA damage of
      stem/progenitor cells in the peripheral blood and bone marrow. To understand the
      related mechanisms, we also measured the levels of intracellular and
      mitochondrial ROS, and 8-OHdG in the plasma and urine, and IL-6 and TNF-alpha in
      the plasma. Compared with the placebo treatment, oral administration of placental
      extract significantly increased the number and colony-forming capacity, but
      decreased the DNA damage of bone marrow stem/progenitor cells. However, neither
      the levels of intracellular and mitochondrial ROS in bone marrow cells, nor the
      levels of 8-OHdG in the urine and plasma significantly differed between groups.
      Interestingly, in comparison with the placebo treatment, placental extract
      significantly decreased the levels of the inflammatory cytokines IL-6 and TNF
      alpha in the plasma. Placental extract significantly attenuated the acute
      radiation injury to bone marrow-derived stem/progenitor cells, and this
      protection is likely to be related to the anti-inflammatory activity of the
      placental extract.

PMID- 23154885
TI  - Repeated administration of centhaquin to pregnant rats did not affect postnatal
      development and expression of endothelin receptors in the brain, heart or kidney
      of pups.
AB  - The effect of repeated administration of centhaquin to pregnant rats on postnatal
      development, and expression of ETA and ETB receptors was determined. Pregnant
      rats were treated daily with either saline or centhaquin for 2 weeks. Male rat
      pups were sacrificed on day 1, 7, 14 and 28 of birth. Brain, kidney and heart
      were removed to study the expression of ETA and ETB receptor protein levels. Body
      weight of pregnant rats increased steadily in both vehicle and centhaquin groups.
      Expression of ETA receptors in the heart and kidney was similar in vehicle and
      centhaquin treated postpartum rats, but was significantly increased in the brain
      of centhaquin treated postpartum rats. No change in expression of ETB receptors
      was observed. In postnatal rats, mean body weight and weights of the brain,
      kidney and heart increased proportionally with advancing age and were similar in
      vehicle and centhaquin groups. The expression of ETA receptors in the brain,
      heart and kidneys was similar in vehicle and centhaquin groups. ETB receptor
      expression significantly (p<0.001) decreased by 72% and 70% on day 28 compared to
      rats of age 1, 7 and 14 days in control and centhaquin groups, respectively.
      Centhaquin treated rats showed similar expression of ETA and ETB receptors
      compared to vehicle treatment. This study suggests that repeated administration
      of centhaquin was well tolerated by pregnant rats that gave birth to normal pups.
      Centhaquin did not affect postnatal development of rats and had similar
      expression of ETA and ETB receptors compared to control pups.

PMID- 23154883
TI  - The nonfermentable dietary fiber hydroxypropyl methylcellulose modulates
      intestinal microbiota.
AB  - Diet influences host metabolism and intestinal microbiota; however, detailed
      understanding of this tripartite interaction is limited. To determine whether the
      nonfermentable fiber hydroxypropyl methylcellulose (HPMC) could alter the
      intestinal microbiota and whether such changes correlated with metabolic
      improvements, C57B/L6 mice were normalized to a high-fat diet (HFD), then either
      maintained on HFD (control), or switched to HFD supplemented with 10% HPMC, or a
      low-fat diet (LFD). Compared to control treatment, both LFD and HPMC reduced
      weight gain (11.8 and 5.7 g, respectively), plasma cholesterol (23.1 and 19.6%),
      and liver triglycerides (73.1 and 44.6%), and, as revealed by 454-pyrosequencing
      of the microbial 16S rRNA gene, decreased microbial alpha-diversity and
      differentially altered intestinal microbiota. Both LFD and HPMC increased
      intestinal Erysipelotrichaceae (7.3- and 12.4-fold) and decreased Lachnospiraceae
      (2.0- and 2.7-fold), while only HPMC increased Peptostreptococcaceae (3.4-fold)
      and decreased Ruminococcaceae (2.7-fold). Specific microorganisms were directly
      linked with weight change and metabolic parameters in HPMC and HFD mice, but not
      in LFD mice, indicating that the intestinal microbiota may play differing roles
      during the two dietary modulations. This work indicates that HPMC is a potential
      prebiotic fiber that influences intestinal microbiota and improves host
      metabolism.

PMID- 23154886
TI  - Synthesis, biological activity and molecular modeling of 4-fluoro-N-[omega
      (1,2,3,4-tetrahydroacridin-9-ylamino)-alkyl]-benzamide derivatives as
      cholinesterase inhibitors.
AB  - The aim of this study was to synthesize and determine the biological activity of
      new derivatives of 4-fluorobenzoic acid and tetrahydroacridine towards inhibition
      of cholinesterases. Compounds were synthesized in condensation reaction between 9
      aminoalkyl-tetrahydroacridines and the activated 4-fluorobenzoic acid. Properties
      towards inhibition of acetyl- and butyrylcholinesterase were estimated according
      to Ellman's spectrophotometric method. Among synthesized compounds the most
      active were compounds 4a and 4d. These compounds, in comparison with tacrine,
      were characterized by the similar values of IC50. Among all obtained compounds,
      4d presented the highest selectivity towards inhibition of acetylcholinesterase.
      Molecular modeling studies revealed that all derivatives presented similar
      extended conformation in the gorge of acetylcholinesterase, however, there were 2
      main conformations in the active center of butyrylcholinesterase: bent and
      extended conformation.

PMID- 23154887
TI  - A validated HPLC method for the determination of eriocalyxin B in plasma and its
      application to pharmacokinetic studies.
AB  - The purpose of this study was to determine EriB in plasma by using the method of
      HPLC and collect the preclinical pharmacokinetic parameters of EriB.The analysis
      involved a simple liquid-liquid extraction. After making alkaline with NaOH,
      plasma was extracted with diethyl ether and the organic extract was then
      evaporated. From there, the residue was reconstituted in to the mobile phase.
      Chromatographic separation was achieved on the C18 column using acetonitrile and
      0.1% triethylamine as mobile phase delivered at 1.0 ml/min. The UV detector
      wavelength was set at 233 nm. Standard curves were linear over the concentration
      range of 50-2 500 ng/ml.The mean predicted concentrations of the quality control
      (QC) samples deviated by less than 3% from the corresponding nominal values; the
      intra-assay and inter-assay precision of the assay were within 10% relative
      standard deviation. The extraction recovery of EriB was more than 80%.The
      developed method has been applied to the pharmacokinetic study of EriB in rats.

PMID- 23154888
TI  - Pharmacokinetics and potential advantages of a new oral solution of levothyroxine
      vs. other available dosage forms.
AB  - To better understand the pharmacokinetics and potential advantages of a
      levothyroxine oral solution vs. tablets and soft gel capsules.4 randomized, 2
      treatment, single-dose (600 mcg levothyroxine), 2-way crossover bioequivalence
      studies in 84 healthy subjects were analyzed. Samples were collected before
      dosing and until 48-72 h post-dose to calculate noncompartmental baseline
      adjusted pharmacokinetic parameters: maximum concentration, time to maximum
      concentration, and area-under-the-concentration-time-curve from 0 to 48 h and
      from 0 to 2 h.Mean pharmacokinetic parameters (+/-standard deviation) for
      tablets, capsules and solution, respectively, were: area-under-the-concentration
      time-curve from 0 to 2 h (ng*h/mL)=68.4+/-32.8, 64.4+/-24.4, 99.1+/-22.7; area
      under-the-concentration-time-curve from 0 to 48 h (ng*h/mL)=1 632+/-424, 1 752+/
      445, 1 862+/-439; maximum concentration (ng/mL)=67.6+/-20.9, 68.0+/-15.9, 71.4+/
      16.0; time of maximum concentration (hours)=2.25+/-0.99, 2.38+/-1.58, 1.96+/
      1.07. Overall rate and extent of exposure were not statistically different
      between formulations, but a faster onset of absorption for the solution was
      suggested (greater area-under-the-concentration-time-curve from 0 to 2 h and
      faster time to maximum concentration by an average of 30 min).Levothyroxine rate
      and extent of exposure are similar between tested formulations. The solution
      appears however to reach systemic circulation quicker as dissolution is not
      needed before absorption starts. The solution's greater early exposure and a
      faster time to maximal concentration of around 30 min may be of benefit to
      minimize drug-food interactions and deserves further investigations.

PMID- 23154889
TI  - High-voltage pyrophosphate cathode: insights into local structure and lithium
      diffusion pathways.
AB  - Ion-transport paths: combined modeling and neutron diffraction studies provide
      atomic-scale insights into Li(2)FeP(2)O(7), a material proposed for a new lithium
      battery cathode with reversible electrode operation at the highest voltage of all
      known Fe-based phosphates. The results indicate that Li(+) ions are transported
      rapidly through a 2D network along the paths shown in green in the picture.

PMID- 23154890
TI  - Men in science.

PMID- 23154893
TI  - Looping in on Ndc80 - how does a protein loop at the kinetochore control
      chromosome segregation?
AB  - Segregation of chromosomes during mitosis requires the interaction of dynamic
      microtubules with the kinetochore, a large protein structure established on the
      centromere region of sister chromatids. The core microtubule-binding activity of
      the kinetochore resides in the KMN network, an outer kinetochore complex. As part
      of the KMN network, the Ndc80 complex, which is composed of Ndc80, Nuf2, Spc24,
      and Spc25, is able to bind directly to microtubules and has the ability to track
      with depolymerizing microtubules to produce chromosome movement. The Ndc80
      complex binds directly to microtubules through a calponin homology domain and an
      unstructured tail in the N terminus of the Ndc80 protein. A recent flurry of
      papers has highlighted the importance of an internal loop region in Ndc80 in
      establishing end-on attachment to microtubules. Here I discuss these recent
      findings that suggest that the Ndc80 internal loop functions as a binding site
      for proteins required for kinetochore-microtubule interactions.

PMID- 23154897
TI  - Comparison of Goldmann applanation and dynamic contour tonometry in a population
      of Mexican open-angle glaucoma patients.
AB  - To compare intraocular pressure (IOP) measurements obtained with Goldmann
      applanation (GAT) and dynamic contour tonometry (DCT) in a Mexican population. 40
      glaucoma patients were included in this cross-sectional observational cohort
      study. IOP measurements were performed in the following order: DCT, ultrasonic
      pachymetry and GAT, with a 5-minute difference between each measurement, between
      8 am and 2 pm. Only DCT measurements of good quality (Q <= 3) were accepted. GAT
      measurements were made three times with the same Goldmann tonometer, previously
      checked for calibration errors, and the mean was used for statistical purposes.
      The IOP (mean [standard deviation], 95 % confidence interval [CI]) measured with
      the Goldmann tonometer (13.2 [2.4], 12.4-14.0 mmHg) was significantly lower than
      that obtained with the DCT (18.4 [3.3], 17.0-19.2 mmHg), p < 0.0001. Pearson's
      correlation coefficients between CCT and IOP measured with GAT and DCT were (r =
      0.24, 95 % CI = 0.07-0.52, p = 0.133) and (r = 0.13, 95 % CI = -0.19 to 0.43, p =
      0.412), respectively. The concordance correlation coefficient between GAT and DCT
      was r c = 0.3, 95 % CI = 0.17-0.41). DCT seems to overestimate the IOP as
      compared to GAT. Additionally, although there was a good correlation between the
      IOP measurements assessed with either GAT or DCT, the agreement was poor.

PMID- 23154898
TI  - Healthcare and the patient experience: harmonizing care and environment.

PMID- 23154899
TI  - Reconsidering the semiprivate inpatient room in u.s. Hospitals.
AB  - In the past 5 years, U. S. hospitals have virtually abandoned the semiprivate
      inpatient room. The inconclusiveness of recent research, however, indicates that
      this room type remains a potentially viable care delivery setting in both
      developed and developing countries for specific patient cohorts and care
      scenarios during hospitalization. Although the U.S. healthcare industry has
      embraced the all-private room hospital, does the semiprivate room have a place at
      all in the 21st-century American hospital? Literature on the subject, both for
      and against, is summarized. This is followed by a proposal for a case study
      prototype and its functional integration within a conventional medical/surgical
      unit in a U.S. hospital. The results suggest that a tempered reintroduction of
      semiprivatism affords opportunities for socialization, patient-family
      transactions and amenities, and staff effectiveness without compromising patient
      safety. Implications for environmental stewardship with respect to the carbon
      neutral hospital of the 21st century are cited, as are priorities for further
      evidence-based design research on this issue.

PMID- 23154900
TI  - Patient-centered care: a healthcare reform imperative and a hospital design
      opportunity.

PMID- 23154901
TI  - The biomechanics of patient room standardization.
AB  - BACKGROUND: The prevailing focus on cognitive load reduction in healthcare
      environment standardization excludes a domain of healthcare delivery that could
      contribute significantly to safety and efficiency through standardization, but it
      has escaped discussion in the context of the biomechanics of care delivery.
      Inappropriate biomechanics not only can harm caregivers but compromise care
      delivery. Little, however, is known regarding the biomechanics of patient care
      and the way it interacts with the configurational issues typically targeted in
      healthcare environment standardization. OBJECTIVES: Examine the types of
      potentially harmful or stressful actions exhibited by nurses during patient care
      delivery in an acute medical/surgical setting. Examine the sources influencing
      unsafe actions. METHOD: Twenty nurses provided three types of simulated care in
      an experimental setting involving nine care configurations that were
      systematically manipulated. A kinesiology expert coded 80 simulation segments
      representing two types of task and two levels of environmental challenge to
      identify potentially stressful and harmful actions. Exploratory and regression
      analyses were conducted on the data. RESULTS: Analysis suggests that a
      considerable proportion of potentially harmful and stressful actions are
      associated with the design of the physical elements as opposed to the
      configurational factors typically addressed in standardization. Both of these
      factors interact to produce work-arounds that result in unsafe actions.
      CONCLUSION: The standardization of healthcare environments needs a larger
      framework to address both cognitive lapses and the biomechanics of care delivery.

PMID- 23154902
TI  - The impact of daylight and views on ICU patients and staff.
AB  - OBJECTIVE: Using a pre-test/post-test quasi-experimental study in two New
      Hampshire ICUs, the impact of daylight and window views on patient pain levels,
      length of stay, staff errors, absenteeism, and vacancy rates were examined. One
      ICU was operational until 2007, the second opened in 2007. ICU patients were
      randomly selected from cardiac surgery, pneumonia, and chronic obstructive
      pulmonary disease admissions of one or more days, 58 from the old ICU, and 52
      from the new. Regular medical staff members assigned to the unit between October
      2006 and September 2007 (old unit) and March 2008 and February 2009 (new unit)
      were included. RESULTS: Variables other than unit design had a more significant
      impact on relative pain levels in each unit. Comparing light levels independent
      of ICU assignment supported the hypothesis that increased light levels reduce
      pain perception and length of stay, but the relationship was not statistically
      significant. One trend, not statistically significant, suggested that view was
      associated with reduced pain perception. A decrease in incident filings supported
      the hypothesis that improved natural light and views reduced errors, but results
      were not statistically significant. Some subcategories demonstrated significance.
      Mean absenteeism per person decreased from 38 to 23 hours from the old unit to
      the new (p = 0.05). Average vacancy rates decreased by 25% (from 10.12% to 7.49%
      staff openings per year) in the old and new units (p = 0.04). CONCLUSION: High
      levels of natural light and window views may positively affect staff absenteeism
      and staff vacancy. Factors such as medical errors, patient pain, and length of
      stay require additional research.

PMID- 23154903
TI  - Impact of imaging room environment: staff job stress and satisfaction, patient
      satisfaction, and willingness to recommend.
AB  - BACKGROUND: The built environment significantly affects the healthcare
      experiences of patients and staff. Healthcare administrators and building
      designers face the opportunity and challenge of improving healthcare experience
      and satisfaction through better environmental design. OBJECTIVE: The purpose of
      the study was to evaluate how a novel environmental intervention for imaging
      rooms, which integrated multiple elements of healing environments including
      positive distractions and personal control over environment, affects the
      perceptions and satisfactions of its primary users-patients and staff. METHODS:
      Anonymous questionnaire surveys were conducted to compare patient and staff
      perceptions of the physical environment, satisfaction, and stress in two types of
      imaging rooms: imaging rooms with the intervention installed (intervention rooms)
      and traditionally designed rooms without the intervention (comparison rooms).
      RESULTS: Imaging technologists and patients perceived the intervention rooms to
      be significantly more pleasant-looking. Patients in the intervention rooms
      reported significantly higher levels of environmental control and were
      significantly more willing to recommend the intervention rooms to others.
      CONCLUSIONS: The environmental intervention was effective in improving certain
      aspects of the imaging environment: pleasantness and environmental control.
      Further improvement of the imaging environment is needed to address problematic
      areas such as noise.

PMID- 23154904
TI  - Wall finish selection in hospital design: a survey of facility managers.
AB  - OBJECTIVE: This paper seeks to analyze healthcare facility managers' perceptions
      regarding the materials used for interior wall finishes and the criteria used to
      select them. It also examines differences in wall finish materials and the
      selection process in three major hospital spaces: emergency, surgery, and in
      patient units. These findings are compared with healthcare designers' perceptions
      on similar issues, as currently documented in the literature. BACKGROUND:
      Hospital design and the materials used for hospital construction have a
      considerable effect on the environment and health of patients. A 2002 survey
      revealed which characteristics healthcare facility designers consider when
      selecting materials for healthcare facilities; however, no similar study has
      examined the views of facility managers on building finish selection. METHODS: A
      22-question survey questionnaire was distributed to 210 facility managers of
      metropolitan, for-profit hospitals in Texas; IRB approval was obtained.
      Respondents were asked to rank 10 interior wall finish materials and 11 selection
      criteria for wall finishes. Data from 48 complete questionnaires were analyzed
      using descriptive statistics and nonparametric statistical analysis methods.
      RESULTS: The study found no statistically significant differences in terms of
      wall finish materials or the characteristics for material selection in the three
      major spaces studied. It identified facility managers' four most-preferred wall
      finish materials and the five-most preferred characteristics, with a statistical
      confidence level of greater than 95%. CONCLUSIONS: The paper underscores the
      importance of incorporating all perspectives: facility designers and facility
      managers should work together toward achieving common organizational goals.

PMID- 23154905
TI  - Perceived neighborhood environments and leisure-time walking among korean adults:
      an application of the theory of planned behavior.
AB  - OBJECTIVE: To examine personal, social, and perceived environmental factors
      related to leisure-time walking behavior among Korean adults using the framework
      of the Theory of Planned Behavior (TPB). BACKGROUND: Sedentary lifestyle and
      physical inactivity contribute to rising obesity rates and chronic diseases among
      Korean adults. Understanding correlates of walking is necessary to develop
      effective interventions to promote regular walking. METHODS: A cross-sectional
      survey was conducted in 2008 among 424 Korean adults. Participants completed a
      questionnaire on perceived neighborhood environment, the TPB constructs, and
      leisure-time walking behavior. RESULTS: Those who participated in leisure-time
      walking had more positive perceptions of aesthetics and expressed greater
      perceived behavioral control (PBC) and intention of walking than nonwalkers.
      Also, walking correlated with intention and PBC, and perceived crime safety.
      Intentions were moderately to strongly associated with attitude, PBC, and
      subjective norm. Integrating TPB constructs and the perceived environment
      variable (crime safety) resulted in a moderate fit of the data [chi(2)= 2.372, df
      = 5; p = 0.796; NFI = 0.99; RMSEA = 0.00] with approximately 45.6% variance of
      intention and 19.4% of the response variance of walking explained. The model
      showed that perceived safety from crime was not directly related to leisure-time
      walking, but indirectly predicted walking through the TPB model. CONCLUSIONS:
      Perceived safety was identified as an important environmental variable among
      Korean adults, and the TPB offered a good prediction of walking behavior.
      Identifying individual, social, and neighborhood environmental correlates of
      walking can help develop policies to promote public health for a more active and
      healthier community.

PMID- 23154906
TI  - Creativity, decision making, and evidence-based design.

PMID- 23154907
TI  - Generating evidence from day-to-day activities: methodological issues-part 2.

PMID- 23154908
TI  - Innovations in hospital architecture.

PMID- 23154909
TI  - Letter to the editors.

PMID- 23154910
TI  - Switching between O- and C-glycosyltransferase through exchange of active-site
      motifs.

PMID- 23154914
TI  - Versatile bottom-up approach to stapled pi-conjugated helical scaffolds:
      synthesis and chiroptical properties of cyclic o-phenylene ethynylene oligomers.
AB  - Spring loaded: the smallest members of a family of carbon nanocoils (CNCs),
      adopting a fixed helical structure, have been synthesized by introduction of one
      or two staples in o-phenylene ethynylene oligomers. The chiroptical responses of
      the systems having enantiopure L-tartrate-derived staples confirmed the induced
      helicity. Theoretical studies suggest that these CNCs are pseudoelastic.

PMID- 23154913
TI  - Effect of a synthetic link N peptide nanofiber scaffold on the matrix deposition
      of aggrecan and type II collagen in rabbit notochordal cells.
AB  - Self-assembling peptide nanofiber scaffolds have been studied extensively as
      biological materials for 3-dimensional cell culture and repairing tissue defects
      in animals. However, few studies have applied peptide nanofiber scaffolds in the
      tissue engineering of intervertebral discs (IVDs). In this study, a novel
      functionalized peptide scaffold was specifically designed for IVD tissue
      engineering, and notochordal cells (NCs) as an alternative cell source for IVD
      degeneration were selected to investigate the bioactive scaffold material. The
      novel RADA16-Link N self-assembling peptide scaffold material was designed by
      direct coupling to a bioactive motif link N. The link N nanofiber scaffold (LN
      NS) material was obtained by mixing pure RADA16-I and RADA16-Link N (1:1)
      designer peptide solutions. Although live/dead cell assays showed that LN-NS and
      RADA16-I scaffold materials were both biocompatible with NCs, the LN-NS material
      significantly promoted NC adhesion compared with that of the pure RADA16-I SAP
      scaffold material. The depositions of aggrecan and type II collagen, which are
      significant markers for IVD cells, were remarkably increased. Furthermore, the
      results indicated that the link N motif, the matrix analog of the nucleus
      pulposus, significantly promoted the accumulation of other extracellular matrices
      in vitro. We conclude that the novel LN-NS material is a promising biological
      scaffold material, and may have a broad range of applications in IVD tissue
      engineering.

PMID- 23154915
TI  - Bohn's nodules: an under-recognised entity.

PMID- 23154916
TI  - Neurodevelopmental outcomes of extremely premature infants conceived after
      assisted conception: a population based cohort study.
AB  - OBJECTIVE: To compare neurodevelopmental outcomes of extremely preterm infants
      conceived after assisted conception (AC) compared with infants conceived
      spontaneously (non-AC). DESIGN: Population-based retrospective cohort study.
      SETTING: Geographically defined area in New South Wales and the Australian
      Capital Territory, Australia served by a network of 10 neonatal intensive care
      units. PATIENTS: Infants <29 weeks' gestation born between 1998 and 2004.
      INTERVENTION: At 2-3 years corrected age, 1473 children were assessed with either
      the Griffiths Mental Developmental Scales or the Bayley Scales of Infant
      Development. MAIN OUTCOME MEASURE: Moderate/severe functional disability defined
      as developmental delay (Griffiths General Quotient or Bayley Mental Developmental
      Index >2 SD below the mean), cerebral palsy (unable to walk without aids),
      deafness (bilateral hearing aids or cochlear implant) or blindness (visual acuity
      <6/60 in the better eye). RESULTS: Mortality and age at follow-up were comparable
      between the AC and non-AC groups. Developmental outcome was evaluated in 217
      (86.5%) AC and 1256 (71.7%) non-AC infants. Using multivariate adjusted analysis,
      infants born after in-vitro fertilisation at 22-26 weeks' gestation (adjusted OR
      1.79, 95% CI 1.05 to 3.05, p=0.03) but not at 27-28 weeks' gestation (adjusted OR
      0.81, 95% CI 0.37 to 1.77; p=0.59) had higher rate of functional disability than
      those born after spontaneous conception. CONCLUSIONS: AC is associated with
      adverse neurodevelopmental outcome among high risk infants born at 22-26 weeks'
      gestation. This finding warrants additional exploration.

PMID- 23154917
TI  - A carborane-derivative "click" reaction under heterogeneous conditions for the
      synthesis of a promising lipophilic MRI/GdBNCT agent.
AB  - In this study, the Huisgen reaction has been used to functionalise a carborane
      cage with a lipophilic moiety and a 1,4,7,10-tetraazacyclododecane-1,4,7,10
      tetraacetic acid (DOTA) ligand to obtain a new Gd boron neutron-capture therapy
      (BNCT)/magnetic resonance imaging (MRI) agent. The introduction of the triazole
      units has been accomplished under both heterogeneous conditions, by the use of a
      Cu-supported ionic-liquid catalyst, and homogeneous conditions. The ability of
      the Gd complex of the synthesised ligand to form stable adducts with low-density
      lipoproteins (LDLs) has been evaluated and then MRI has been performed on tumour
      melanoma cells incubated in the presence of a Gd-complex/LDL imaging probe. It
      has been concluded that the high amount of intracellular boron necessary to
      perform BNCT can be reached even in the presence of a relatively low-boron
      containing LDL concentration.

PMID- 23154918
TI  - Cardiac output measured by uncalibrated arterial pressure waveform analysis by
      recently released software version 3.02 versus thermodilution in septic shock.
AB  - To evaluate the 3.02 software version of the FloTrac/VigileoTM system for
      estimation of cardiac output by uncalibrated arterial pressure waveform analysis,
      in septic shock. Nineteen consecutive patients in septic shock were studied.
      FloTrac/VigileoTM measurements (COfv) were compared with pulmonary artery
      catheter thermodilution-derived cardiac output (COtd). The mean cardiac output
      was 7.7 L min(-1) and measurements correlated at r = 0.53 (P < 0.001, n = 314).
      In Bland-Altman plot for repeated measurements, the bias was 1.7 L min(-1) and 95
      % limits of agreement (LA) were -3.0 to 6.5 L min(-1), with a %error of 53 %. The
      bias of COfv inversely related to systemic vascular resistance (SVR) (r = -0.54,
      P < 0.001). Above a SVR of 700 dyn s cm(-5) (n = 74), bias was 0.3 L min(-1) and
      95 % LA were -1.6 to 2.2 L min(-1) (%error 32 %). Changes between consecutive
      measurements (n = 295) correlated at 0.67 (P < 0.001), with a bias of 0.1 % (95 %
      limits of agreement -17.5 to 17.0 %). All changes >10 % in both COtd and COfv (n
      = 46) were in the same direction. Eighty-five percent of the measurements were
      within the 30 degrees -330 degrees  of the polar axis. COfv with the latest
      software still underestimates COtd at low SVR in septic shock. The tracking
      capacities of the 3.02 software are moderate-good when clinically relevant
      changes are considered.

PMID- 23154923
TI  - Intrinsically copper-64-labeled organic nanoparticles as radiotracers.
AB  - PET friendly: labels for PET imaging are incorporated into completely organic
      porphysomes by using a fast (30 min), one-pot, high-yielding (>95 %) procedure to
      produce highly stable (>48 h) radiolabeled nanoparticles that show the highest
      specific activity ever reported for a (64) Cu-labeled nanoparticle. These (64) Cu
      porphysomes can be accurately and noninvasively tracked in vivo.

PMID- 23154924
TI  - Toward libraries of biotinylated chondroitin sulfate analogues: from synthesis to
      in vivo studies.
AB  - Chondroitin sulfate-E (CS-E) oligosaccharidic analogues (di to hexa) were
      prepared from lactose. In these compounds, the 2-acetamido group was replaced by
      a hydroxyl group. This modification speeded up the synthesis, and large
      oligosaccharides were constructed in a few steps from a lactose-originated block.
      The protecting groups used were as follows; Fmoc for hydroxyl groups to be
      glycosylated, allyl group for anomeric position protection, and
      trichoroacetimidate leaving groups were used to prepare up to octasaccharides. We
      took advantage of the presence of allyl group to develop a click biotinylation,
      through its transformation into a 3-azido-2-hydroxyl propyl group in two steps
      (epoxidation and sodium azide epoxide opening). The biotinylating agent was a
      water-soluble propargylated and biotinylated triethylene glycol (PEG). By using
      surface plasmon resonance (SPR), it was shown that the di-, tetra-, and
      hexasaccharides display a binding affinity and selectivity toward HSF/GSF and
      CXCL12 similar to that of CS-E. A parallel study confirmed their mimicry of
      natural compounds, based on the hexasaccharide interaction with Otx2, a
      homeodomain protein involved in brain maturation, thus validating our
      simplification approach to synthesize bioactive GAG.

PMID- 23154925
TI  - Encephalopathy and liver transplantation.
AB  - Liver transplantation (LT) candidates experience frequently episodic or
      persistent hepatic encephalopathy. In addition, these patients can exhibit
      neurological comorbidities that contribute to cognitive impairment in the pre
      transplant period. Assessment of the respective contribution of hepatic
      encephalopathy or comorbidities in the cognitive manifestations is critical to
      estimate the neurological benefits of restoring liver function. Magnetic
      resonance imaging and spectroscopy are useful to assess the impact of liver
      failure or comorbidities. This assessment is critical to decide liver transplant
      in difficult cases. In the early postoperative period, LT is commonly complicated
      by a confusional syndrome. The possible role of persisting hepatic encephalopathy
      in its development has not been clearly established. The origin is usually
      considered multifactorial and relates to complications following LT, such as
      infections, rejection, primary liver dysfunction, immunosuppressors, etc.... The
      diagnosis and treatment is based in the recognition of comorbidities and optimal
      care of metabolic disturbances. Several studies have demonstrated recovery of
      cognitive function after LT in patients that have exhibited hepatic
      encephalopathy. However, some deficits may persist specifically among patients
      with persistent HE. Other factors present before LT that contribute to a worse
      neuropsychological outcome after LT are diabetes mellitus and alcohol
      consumption. Long-term after LT, cognitive function may worsen in relation to
      vascular risk factors.

PMID- 23154926
TI  - Dyskinesia associated with hyperglycemia and basal ganglia hyperintensity: report
      of a rare diabetic complication.
AB  - The syndrome of dyskinesia associated with hyperglycemia and basal ganglia
      hyperintensity on T1 - weighted MR images is rare and most often affects elderly
      patients with type 2 diabetes. We report a case of a 79 year-old female patient
      who presented to the ED with a 12 h history of a left sided hemichoreoathetosis.
      Laboratory results revealed pronounced nonketotic hyperglycemia [27 mmol/L (486
      mg/dL); HbA1c 140 mmol/mol (15 %)] and brain MRI showed bilateral T1
      hyperintensity in the basal ganglia, more noticeable on the right side. One week
      before she had been admitted with a diagnosis of transient ischemic attack
      consisting in left hemiparesthesia, also with nonketotic hyperglycemia [38.9
      mmol/L (700 mg/dL)] and was discharged home with partial correction of her
      metabolic disturbance. The movement disorder did not improve with adequate
      glycemic control so haloperidol was started. Six weeks later she was seen on an
      outpatient basis. She still had minimal residual involuntary movements of the
      left arm and leg. Laboratory exams revealed a well controlled diabetes mellitus
      [glycemia 6.0 mmol/L (109 mg/dL), HbA1c 57 mmol/mol (7.4 %)]. In conclusion, the
      syndrome of dyskinesia associated to hyperglycemia and hyperintensity in the
      basal ganglia on T1 - weighted MR images is a rare, intriguing and yet
      incompletely understood complication of diabetes mellitus. The increasing number
      of reported cases may help to better understand its peculiarities such as the
      existence of a clear clinical radiological dissociation and to unveil
      pathophysiological aspects. We suggest the possibility that the metabolic
      disturbances unmask a previous established asymptomatic striatum vasculopathy.

PMID- 23154927
TI  - Age-dependent deficits in fear learning in heterozygous BDNF knock-out mice.
AB  - Beyond its trophic function, the neurotrophin BDNF (brain-derived neurotrophic
      factor) is well known to crucially mediate synaptic plasticity and memory
      formation. Whereas recent studies suggested that acute BDNF/TrkB signaling
      regulates amygdala-dependent fear learning, no impairments of cued fear learning
      were reported in heterozygous BDNF knock-out mice (BDNF(+/-)). Since brain BDNF
      levels are known to decline with aging, we hypothesized that BDNF(+/-) mice might
      show reduced fear learning at older ages. Indeed, BDNF(+/-) animals revealed an
      age-dependent deficit in fear learning 3 mo after birth and beyond. Since there
      were no alterations between the two genotypes during the conditioning training
      and when testing short-term memory, this learning deficit most likely reflects a
      deficit in memory consolidation. Importantly, there were no differences in
      spontaneous motor behavior and baseline anxiety in BDNF(+/-) animals at any age
      tested. Following behavioral testing quantification of BDNF levels in the
      basolateral amygdala with a sensitive BDNF ELISA revealed a positive correlation
      between the levels of BDNF in the amygdala and the individual learning
      performance. However, the age-dependent decline in the efficiency of fear
      conditioning in BDNF(+/-) mice was not accompanied by reduced BDNF expression in
      the amygdala. Thus, while reduced BDNF levels in general correlate with less
      efficient fear learning, this lack of BDNF can be compensated in young but not in
      older animals, suggesting that the cellular mechanisms responsible for fear
      learning consolidation become BDNF-dependent 3 mo after birth.

PMID- 23154929
TI  - The episodic engram transformed: Time reduces retrieval-related brain activity
      but correlates it with memory accuracy.
AB  - We took snapshots of human brain activity with fMRI during retrieval of realistic
      episodic memory over several months. Three groups of participants were scanned
      during a memory test either hours, weeks, or months after viewing a documentary
      movie. High recognition accuracy after hours decreased after weeks and remained
      at similar levels after months. In contrast, BOLD activity in a retrieval-related
      set of brain areas during correctly remembered events was similar after hours and
      weeks but significantly declined after months. Despite this reduction, BOLD
      activity in retrieval-related regions was positively correlated with recognition
      accuracy only after months. Hippocampal engagement during retrieval remained
      similar over time during recall but decreased in recognition. Our results are in
      line with the hypothesis that hippocampus subserves retrieval of real-life
      episodic memory long after encoding, its engagement being dependent on retrieval
      demands. Furthermore, our findings suggest that over time episodic engrams are
      transformed into a parsimonious form capable of supporting accurate retrieval of
      the crux of events, arguably a critical goal of memory, with only minimal network
      activation.

PMID- 23154928
TI  - Fan-shaped body neurons are involved in period-dependent regulation of long-term
      courtship memory in Drosophila.
AB  - In addition to its established function in the regulation of circadian rhythms,
      the Drosophila gene period (per) also plays an important role in processing long
      term memory (LTM). Here, we used courtship conditioning as a learning paradigm
      and revealed that (1) overexpression and knocking down of per in subsets of brain
      neurons enhance and suppress LTM, respectively, and (2) suppression of synaptic
      transmission during memory retrieval in the same neuronal subsets leads to
      defective LTM. Further analysis strongly suggests that the brain region critical
      for per-dependent LTM regulation is the fan-shaped body, which is involved in
      sleep-induced enhancement of courtship LTM.

PMID- 23154930
TI  - Metallo-foldamers with backbone-coordinative oxime peptides: control of secondary
      structures.
AB  - Metal-mediated secondary structures of peptide-based foldamers were constructed
      using artificial backbone-coordinative oxime peptides. Complexation of the
      peptides with Pd(II) afforded several mononuclear and dinuclear secondary
      structures such as helices and hairpins as confirmed by single-crystal XRD and
      NMR analyses.

PMID- 23154931
TI  - Highly enantioselective intermolecular Stetter reaction of simple acrylates:
      synthesis of alpha-chiral gamma-ketoesters.
AB  - Simple Stetter: A novel N-heterocyclic carbene (NHC) was designed by combining an
      electron-rich 2,6-dimethoxy substituent and an underestimated yet promising
      chiral motif. With this NHC in hand, a highly enantioselective intermolecular
      Stetter reaction of simple acrylates was developed, yielding versatile alpha
      chiral gamma-ketoesters. This represents the first catalytic asymmetric route
      towards these valuable compounds (see scheme).

PMID- 23154932
TI  - Total structure and electronic properties of the gold nanocrystal Au36(SR)24.
AB  - A golden opportunity: the total structure of a Au(36)(SR)(24) nanocluster reveals
      an unexpected face-centered-cubic tetrahedral Au(28) kernel (magenta). The
      protecting layer exhibits an intriguing combination of binding modes, consisting
      of four regular arch-like staples and the unprecedented appearance of twelve
      bridging thiolates (yellow). This unique protecting network and superatom
      electronic shell structure confer extreme stability and robustness.

PMID- 23154933
TI  - Adaptation of stem cells to 96-well plate assays: use of human embryonic and
      mouse neural stem cells in the MTT assay.
AB  - Human embryonic stem cells (hESC) are difficult to adapt to 96-well plate assays,
      such as the MTT assay, because they survive best when plated as colonies, which
      are not easily counted and plated accurately. Two methods were developed to
      address this problem. In the first, ROCK inhibitor (ROCKi) was used, which allows
      accurate counting and plating of single hESC. In the second, small colonies were
      plated without ROCKi but with adaptations for accurate counting and plating. The
      MTT assay was also adapted for use with mouse neural stem cells. These methods
      allow the MTT assay to be conducted rapidly and accurately with high
      reproducibility between replicate experiments. When screening volatile chemicals
      in a 96-well plate, vapor effects may occur and dose ranges must be carefully
      defined. The methods were validated using the NIH assay guidance tool. These
      methodss could readily be translated to other 96-well plate assay.

PMID- 23154934
TI  - Serum-free generation of multipotent mesoderm (Kdr+) progenitor cells in mouse
      embryonic stem cells for functional genomics screening.
AB  - This unit describes a robust protocol for producing multipotent Kdr-expressing
      mesoderm progenitor cells in serum-free conditions, and for functional genomics
      screening using these cells. Kdr-positive cells are able to differentiate into a
      wide array of mesodermal derivatives, including vascular endothelial cells,
      cardiomyocytes, hematopoietic progenitors, and smooth muscle cells. The efficient
      generation of such progenitor cells is of particular interest because it permits
      subsequent steps in cardiovascular development to be analyzed in detail,
      including deciphering the mechanisms that direct differentiation. In addition,
      the oligonucleotide transfection protocol used to functionally screen siRNA and
      miRNA libraries is a powerful tool to reveal networks of genes, signaling
      proteins, and miRNAs that control the diversification of cardiovascular lineages
      from multipotent progenitors. Technical limitations, troubleshooting, and
      potential applications of these methods are discussed.

PMID- 23154935
TI  - Functional stem cell integration assessed by organotypic slice cultures.
AB  - Re-formation or preservation of functional, electrically active neural networks
      has been proffered as one of the goals of stem cell-mediated neural therapeutics.
      A primary issue for a cell therapy approach is the formation of functional
      contacts between the implanted cells and the host tissue. Therefore, it is of
      fundamental interest to establish protocols that allow us to delineate a detailed
      time course of grafted stem cell survival, migration, differentiation,
      integration, and functional interaction with the host. One option for in vitro
      studies is to examine the integration of exogenous stem cells into an existing
      active neuronal network in ex vivo organotypic cultures. Organotypic cultures
      leave the structural integrity essentially intact while still allowing the
      microenvironment to be carefully controlled. This allows detailed studies over
      time of cellular responses and cell-cell interactions, which are not readily
      performed in vivo. This unit describes procedures for using organotypic slice
      cultures as ex vivo model systems for studying neural stem cell and embryonic
      stem cell engraftment and communication with CNS host tissue.

PMID- 23154936
TI  - Genetic manipulation of human induced pluripotent stem cells.
AB  - Human induced pluripotent stem cells (HIPSC) have tremendous value as a source of
      autologous cells for cellular transplantation in the treatment of degenerative
      diseases. The protocols described here address methods for large-scale genetic
      modification of HIPSCs. The first is an optimized method for transfecting HIPSCs
      cultured in feeder-free conditions. The second method allows nucleofection of
      trypsinized HIPSCs at an optimal cell density. Both methods enable robust
      generation of stable HIPSC transfectants within two weeks. Our protocols are
      highly reproducible and do not require optimization for individual HIPSC and
      human embryonic stem cell (HESC) lines.

PMID- 23154937
TI  - Nitrogen-rich bis-1,2,4-triazoles-a comparative study of structural and energetic
      properties.
AB  - In this contribution, the synthesis and full structural and spectroscopic
      characterization of five bis-1,2,4-triazoles in combination with different
      energetic moieties like amino, nitro, nitrimino, azido, and dinitromethylene
      groups is presented. The main goal is a comparative study on the influence of
      those energetic moieties on the structural and energetic properties. A complete
      characterization including IR, Raman, and multinuclear NMR spectroscopy of all
      compounds is presented. Additionally, X-ray crystallographic measurements were
      performed and deliver insight into structural characteristics as well as inter-
      and intramolecular interactions. The standard enthalpies of formation were
      calculated for all compounds at the CBS-4M level of theory, the detonation
      parameters were calculated by using the EXPLO5.05 program. Additionally, the
      impact as well as the friction sensitivities and the sensitivity against
      electrostatic discharge were determined. The potential application of the
      synthesized compounds as energetic material will be studied and evaluated by
      using the experimentally obtained values for the thermal decomposition, the
      sensitivity data, and the calculated performance characteristics.

PMID- 23154939
TI  - Asthma exacerbations: a molecular dichotomy between antiviral and pro
      inflammatory responses revealed.

PMID- 23154940
TI  - Activation of canonical wnt pathway promotes differentiation of mouse bone marrow
      derived MSCs into type II alveolar epithelial cells, confers resistance to
      oxidative stress, and promotes their migration to injured lung tissue in vitro.
AB  - The differentiation of mesenchymal stem cells (MSCs) into type II alveolar
      epithelial (AT II) cells in vivo and in vitro, is critical for reepithelization
      and recovery in acute lung injury (ALI), but the mechanisms responsible for
      differentiation are unclear. In the present study, we investigated the role of
      the canonical wnt pathway in the differentiation of mouse bone marrow-derived
      MSCs (mMSCs) into AT II cells. Using a modified co-culture system with murine
      lung epithelial-12 (MLE-12) cells and small airway growth media (SAGM) to
      efficiently drive mMSCs differentiation, we found that GSK 3beta and beta-catenin
      in the canonical wnt pathway were up-regulated during differentiation. The levels
      of surfactant protein (SP) C, SPB, and SPD, the specific markers of AT II cells,
      correspondingly increased in mMSCs when Wnt3a or LiCl was added to the co-culture
      system to activate wnt/beta-catenin signaling. The expression of these factors
      was depressed to some extent by inhibiting the pathway with the addition of DKK
      1. The differentiation rate of mMSCs also depends on their abilities to
      accumulate and survive in inflammatory tissue. Our results suggested that the
      activation of wnt/beta-catenin signaling promoted mMSCs migration towards ALI
      mouse-derived lung tissue in a Transwell assay, and ameliorated the cell death
      and the reduction of Bcl-2/Bax induced by H(2) O(2), which simultaneously caused
      reduced GSK 3beta and beta-catenin in mMSCs. These data supports a potential
      mechanism for the differentiation of mMSCs into AT II cells involving canonical
      wnt pathway activation, which may be significant to their application in ALI.

PMID- 23154938
TI  - Noise-induced inner hair cell ribbon loss disturbs central arc mobilization: a
      novel molecular paradigm for understanding tinnitus.
AB  - Increasing evidence shows that hearing loss is a risk factor for tinnitus and
      hyperacusis. Although both often coincide, a causal relationship between tinnitus
      and hyperacusis has not been shown. Currently, tinnitus and hyperacusis are
      assumed to be caused by elevated responsiveness in subcortical circuits. We
      examined both the impact of different degrees of cochlear damage and the
      influence of stress priming on tinnitus induction. We used (1) a behavioral
      animal model for tinnitus designed to minimize stress, (2) ribbon synapses in
      inner hair cells (IHCs) as a measure for deafferentation, (3) the integrity of
      auditory brainstem responses (ABR) to detect differences in stimulus-evoked
      neuronal activity, (4) the expression of the activity-regulated cytoskeletal
      protein, Arc, to identify long-lasting changes in network activity within the
      basolateral amygdala (BLA), hippocampal CA1, and auditory cortex (AC), and (5)
      stress priming to investigate the influence of corticosteroid on trauma-induced
      brain responses. We observed that IHC ribbon loss (deafferentation) leads to
      tinnitus when ABR functions remain reduced and Arc is not mobilized in the
      hippocampal CA1 and AC. If, however, ABR waves are functionally restored and Arc
      is mobilized, tinnitus does not occur. Both central response patterns were found
      to be independent of a profound threshold loss and could be shifted by the
      corticosterone level at the time of trauma. We, therefore, discuss the findings
      in the context of a history of stress that can trigger either an adaptive or
      nonadaptive brain response following injury.

PMID- 23154941
TI  - Site-specific labeling of proteins with a chemically stable, high-affinity tag
      for protein study.
AB  - Site-specific labeling of proteins with paramagnetic lanthanides offers unique
      opportunities by virtue of NMR spectroscopy in structural biology. In particular,
      these paramagnetic data, generated by the anisotropic paramagnetism including
      pseudocontact shifts (PCS), residual dipolar couplings (RDC), and paramagnetic
      relaxation enhancement (PRE), are highly valuable in structure determination and
      mobility studies of proteins and protein-ligand complexes. Herein, we present a
      new way to label proteins in a site-specific manner with a high-affinity and
      chemically stable tag, 4-vinyl(pyridine-2,6-diyl)bismethylenenitrilo
      tetrakis(acetic acid) (4VPyMTA), through thiol alkylation. Its performance has
      been demonstrated in G47C and E64C mutants of human ubiquitin both in vitro and
      in a crowded environment. In comparison with the published tags, 4VPyMTA has
      several interesting features: 1) it has a very high binding affinity for
      lanthanides (higher than EDTA), 2) there is no heterogeneity in complexes with
      lanthanides, 3) the derivatized protein is stable and potentially applicable to
      the in situ analysis of proteins.

PMID- 23154942
TI  - Controlled synthesis of BiOCl hierarchical self-assemblies with highly efficient
      photocatalytic properties.

PMID- 23154944
TI  - Conjugate addition versus cycloaddition/condensation of nitro compounds in water:
      selectivity, acid-base catalysis, and induction period.
AB  - Nitroacetates and nitroacetamides react in water as in chloroform with electron
      deficient dipolarophiles to give condensation or conjugate addition products
      under base catalysis. In general, high selectivity towards condensation is
      observed in water, with shorter induction periods than in chloroform. In water,
      condensations slowly occur even without base; kinetic profiles evidence the
      catalytic effect of the base, which should be related to the conversion into the
      tautomer nitronic acid. Condensations in water provide convenient access to
      isoxazole derivatives bearing various functional groups including ammonium,
      carboxy, and carboxyamide.

PMID- 23154945
TI  - I. Changes and challenges revisited.

PMID- 23154943
TI  - Transient acidification and subsequent proinflammatory cytokine stimulation of
      astrocytes induce distinct activation phenotypes.
AB  - The foot processes of astrocytes cover over 60% of the surface of brain
      microvascular endothelial cells, regulating tight junction integrity. Retraction
      of astrocyte foot processes has been postulated to be a key mechanism in
      pathology. Therefore, movement of an astrocyte in response to a proinflammatory
      cytokine or even limited retraction of processes would result in leaky junctions
      between endothelial cells. Astrocytes lie at the gateway to the CNS and are
      instrumental in controlling leukocyte entry. Cultured astrocytes typically have a
      polygonal morphology until stimulated. We hypothesized that cultured astrocytes
      which were induced to stellate would have an activated phenotype compared with
      polygonal cells. We investigated the activation of astrocytes derived from adult
      macaques to the cytokine TNF-alpha under resting and stellated conditions by four
      parameters: morphology, intermediate filament expression, adhesion, and cytokine
      secretion. Astrocytes were stellated following transient acidification; resulting
      in increased expression of GFAP and vimentin. Stellation was accompanied by
      decreased adhesion that could be recovered with proinflammatory cytokine
      treatment. Surprisingly, there was decreased secretion of proinflammatory
      cytokines by stellated astrocytes compared with polygonal cells. These results
      suggest that astrocytes are capable of multiple phenotypes depending on the
      stimulus and the order stimuli are applied.

PMID- 23154946
TI  - II. Lateral tilt at Caesarean section: one angle fits all or made-to-measure?

PMID- 23154947
TI  - Litigation in anaesthesia: areas of high clinical risk and the National Audit
      Projects.

PMID- 23154949
TI  - What is an adequate measure of lung function?

PMID- 23154951
TI  - Decision support system combined with automated reminders for postoperative
      nausea and vomiting prophylaxis.

PMID- 23154953
TI  - Goal-directed therapy: each therapeutic regimen needs its indication.

PMID- 23154955
TI  - Levosimendan in a case of severe peri-myocarditis associated with influenza
      A/H1N1 virus.

PMID- 23154956
TI  - Do old pharmacokinetic parameter estimates predict new data?

PMID- 23154957
TI  - Videolaryngoscopy allows a better view of the pharynx and larynx than classic
      laryngoscopy.

PMID- 23154962
TI  - The predictive validity of subjective mortality expectations: evidence from the
      Health and Retirement Study.
AB  - Several recent studies suggest that individual subjective survival forecasts are
      powerful predictors of both mortality and behavior. Using 15 years of
      longitudinal data from the Health and Retirement Study, I present an alternative
      view. Across a wide range of ages, predictions of in-sample mortality rates based
      on subjective forecasts are substantially less accurate than predictions based on
      population life tables. Subjective forecasts also fail to capture fundamental
      properties of senescence, including increases in yearly mortality rates with age.
      To shed light on the mechanisms underlying these biases, I develop and estimate a
      latent-factor model of how individuals form subjective forecasts. The estimates
      of this model's parameters imply that these forecasts incorporate several
      important sources of measurement error that arguably swamp the useful information
      they convey.

PMID- 23154963
TI  - Mechanism of ketone allylation with allylboronates as catalyzed by zinc
      compounds: a DFT study.
AB  - The mechanism of the allylation reaction between 4-chloroacetophenone and pinacol
      allylboronates catalyzed by ZnEt(2) with alcohols was investigated using density
      functional theory (DFT) at the M05-2X/6-311++G(d,p) level. The calculations
      reveal that the reaction prefers to proceed through a double gamma-addition
      stepwise reaction mechanism rather than a Lewis acid-catalyzed concerted one. The
      intermediate with a four-coordinated boron center, which is formed through proton
      transfer from EtOH to the ethyl group of ZnEt(2) mediated by the boron center, is
      the active species and an entrance for the catalytic cycle. The latter is
      composed of three elementary steps: 1) boron to zinc transmetalation leading to
      the formation of allylzincate species, 2) electrophilic addition of ketone to
      allylzincate species, and 3) generation of the final product with recovery of the
      catalyst. The boron to zinc transmetalation step has the largest energy barrier
      of 61.0 kJ mol(-1) and is predicted to be the rate-determining step. The
      calculations indicate that the additive EtOH plays important roles both in
      lowering the activation free energy for the formation of the four-coordinated
      boron active intermediate and in transforming the low catalytic activity ZnEt(2)
      into high activity zinc alkoxide species. The alcohols with a less sterically
      encumbering R group might be the effective additives. The substituted groups on
      the allylboronates might primarily affect the boron to zinc transmetalation, and
      the allylboronates with substituents on the C(gamma)  atom is poor in reactivity.
      The comparison of the catalytic effect between the zinc compounds investigated
      suggest that Zn(OEt)(2), Zn(OH)(2), and ZnF(2) exhibit higher catalytic
      efficiency for the boron to zinc transmetalation due to the activation of the B
      C(alpha) bond through orbital interactions between the p orbitals of the EtO, OH,
      F groups and the empty p orbital of the boron center.

PMID- 23154964
TI  - Metal-ion metathesis in metal-organic frameworks: a synthetic route to new metal
      organic frameworks.
AB  - A porous metal-organic framework, Mn(H(3)O)[(Mn(4)Cl)(3)(hmtt)(8)] (POST-65), was
      prepared by the reaction of 5,5',10,10',15,15'-hexamethyltruxene-2,7,12
      tricarboxylic acid (H(3)hmtt) with MnCl(2) under solvothermal conditions. POST
      65(Mn) was subjected to post-synthetic modification with Fe, Co, Ni, and Cu
      according to an ion-exchange method that resulted in the formation of three
      isomorphous frameworks, POST-65(Co/Ni/Cu), as well as a new framework, POST
      65(Fe). The ion-exchanged samples could not be prepared by regular solvothermal
      reactions. The complete exchange of the metal ions and retention of the framework
      structure were verified by inductively coupled plasma-atomic emission
      spectrometry (ICP-AES), powder X-ray diffraction (PXRD), and Brunauer-Emmett
      Teller (BET) surface-area analysis. Single-crystal X-ray diffractions studies
      revealed a single-crystal-to-single-crystal (SCSC)-transformation nature of the
      ion-exchange process. Hydrogen-sorption and magnetization measurements showed
      metal-specific properties of POST-65.

PMID- 23154966
TI  - New reactivity of the uranyl(VI) ion.
AB  - The chemistry of the uranyl ion ([UO(2)](2+)) has evolved remarkably over the
      past few years, with unexpected reactivity observed that challenge our
      understanding of this ion, and of actinides in general. This review highlights
      some recent advances in the field, focussing on the organometallic chemistry of
      the uranyl moiety, which is not well developed in comparison to lower oxidation
      states of uranium. The use of uranyl as a catalyst is highlighted and the newly
      developed supramolecular chemistry is described. The uranyl oxygen atoms have
      been considered as inert, but recent work has shown that is not necessarily the
      case and is discussed herein. Finally, reduction to the [UO(2)](+) ion will be
      discussed.

PMID- 23154965
TI  - Cancer-Specific requirement for BUB1B/BUBR1 in human brain tumor isolates and
      genetically transformed cells.
AB  - To identify new candidate therapeutic targets for glioblastoma multiforme, we
      combined functional genetics and glioblastoma network modeling to identify
      kinases required for the growth of patient-derived brain tumor-initiating cells
      (BTIC) but that are dispensable to proliferating human neural stem cells (NSC).
      This approach yielded BUB1B/BUBR1, a critical mitotic spindle checkpoint player,
      as the top-scoring glioblastoma lethal kinase. Knockdown of BUB1B inhibited
      expansion of BTIC isolates, both in vitro and in vivo, without affecting
      proliferation of NSCs or astrocytes. Mechanistic studies revealed that BUB1B's
      GLE2p-binding sequence (GLEBS) domain activity is required to suppress lethal
      kinetochore-microtubule (KT-MT) attachment defects in glioblastoma isolates and
      genetically transformed cells with altered sister KT dynamics, which likely favor
      KT-MT instability. These results indicate that glioblastoma tumors have an added
      requirement for BUB1B to suppress lethal consequences of altered KT function and
      further suggest that sister KT measurements may predict cancer-specific
      sensitivity to BUB1B inhibition and perhaps other mitotic targets that affect KT
      MT stability. SIGNIFICANCE: Currently, no effective therapies are available for
      glioblastoma, the most frequent and aggressive brain tumor. Our results suggest
      that targeting the GLEBS domain activity of BUB1B may provide a therapeutic
      window for glioblastoma, as the GLEBS domain is nonessential in untransformed
      cells. Moreover, the results further suggest that sister KT distances at
      metaphase may predict sensitivity to anticancer therapeutics targeting KT
      function.

PMID- 23154968
TI  - Staphylococcus aureus protein A binding to osteoblast tumour necrosis factor
      receptor 1 results in activation of nuclear factor kappa B and release of
      interleukin-6 in bone infection.
AB  - Staphylococcus aureus is the major pathogen among the staphylococci and the most
      common cause of bone infections. These infections are mainly characterized by
      bone destruction and inflammation, and are often debilitating and very difficult
      to treat. Previously we demonstrated that S. aureus protein A (SpA) can bind to
      osteoblasts, which results in inhibition of osteoblast proliferation and
      mineralization, apoptosis, and activation of osteoclasts. In this study we used
      small interfering RNA (siRNA) to demonstrate that osteoblast tumour necrosis
      factor receptor-1 (TNFR-1) is responsible for the recognition of and binding to
      SpA. TNFR-1 binding to SpA results in the activation of nuclear factor kappa B
      (NFkappaB). In turn, NFkappaB translocates to the nucleus of the osteoblast,
      which leads to release of interleukin 6 (IL-6). Silencing TNFR-1 in osteoblasts
      or disruption of the spa gene in S. aureus prevented both NFkappaB activation and
      IL-6 release. As well as playing a key role in proinflammatory reactions, IL-6 is
      also an important osteotropic factor. Release of IL-6 from osteoblasts results in
      the activation of the bone-resorbing cells, the osteoclasts. Consistent with our
      results described above, both silencing TNFR-1 in osteoblasts and disruption of
      spa in S. aureus prevented osteoclast activation. These studies are the first to
      demonstrate the importance of the TNFR-1-SpA interaction in bone infection, and
      may help explain the mechanism through which osteoclasts become overactivated,
      leading to bone destruction. Anti-inflammatory drug therapy could be used either
      alone or in conjunction with antibiotics to treat osteomyelitis or for
      prophylaxis in high-risk patients.

PMID- 23154967
TI  - bZIP transcription factors affecting secondary metabolism, sexual development and
      stress responses in Aspergillus nidulans.
AB  - The eukaryotic basic leucine zipper (bZIP) transcription factors play critical
      roles in the organismal response to the environment. Recently, a novel YAP-like
      bZIP, restorer of secondary metabolism A (RsmA), was found in a suppressor screen
      of an Aspergillus nidulans secondary metabolism (SM) mutant in which
      overexpression of rsmA was found to partially remediate loss of SM in Velvet
      Complex mutants. The Velvet Complex is a conserved fungal transcriptional
      heteromer that couples SM with sexual development in fungi. Here we characterized
      and contrasted SM in mutants of RsmA and four other A. nidulans bZIP proteins
      (NapA, ZipA, ZipB and ZipC) with predicted DNA binding motifs similar to RsmA.
      Only two overexpression mutants exhibited both SM and sexual abnormalities that
      were noteworthy: OE : : rsmA resulted in a 100-fold increase in sterigmatocystin
      and a near loss of meiotic spore production. OE : : napA displayed decreased
      production of sterigmatocystin, emericellin, asperthecin, shamixanthone and
      epishamixanthone, coupled with a shift from sexual to asexual development.
      Quantification of bZIP homodimer and heterodimer formation using fluorescence
      resonance energy transfer (FRET) suggested that these proteins preferentially
      self-associate.

PMID- 23154970
TI  - Transcriptome changes initiated by carbon starvation in Aspergillus nidulans.
AB  - Carbon starvation is a common stress for micro-organisms both in nature and in
      industry. The carbon starvation stress response (CSSR) involves the regulation of
      several important processes including programmed cell death and reproduction of
      fungi, secondary metabolite production and extracellular hydrolase formation. To
      gain insight into the physiological events of CSSR, DNA microarray analyses
      supplemented with real-time RT-PCR (rRT-PCR) experiments on 99 selected genes
      were performed. These data demonstrated that carbon starvation induced very
      complex changes in the transcriptome. Several genes contributing to protein
      synthesis were upregulated together with genes involved in the unfolded protein
      stress response. The balance between biosynthesis and degradation moved towards
      degradation in the case of cell wall, carbohydrate, lipid and nitrogen
      metabolism, which was accompanied by the production of several hydrolytic enzymes
      and the induction of macroautophagy. These processes provide the cultures with
      long-term survival by liberating nutrients through degradation of the cell
      constituents. The induced synthesis of secondary metabolites, antifungal enzymes
      and proteins as well as bacterial cell wall-degrading enzymes demonstrated that
      carbon-starving fungi should have marked effects on the micro-organisms in their
      surroundings. Due to the increased production of extracellular and vacuolar
      enzymes during carbon starvation, the importance of the endoplasmic reticulum
      increased considerably.

PMID- 23154969
TI  - Insertion mutations in Helicobacter pylori flhA reveal strain differences in RpoN
      dependent gene expression.
AB  - Flagellar biogenesis in the gastric pathogen Helicobacter pylori involves a
      transcriptional hierarchy that utilizes all three sigma factors found in this
      bacterium (RpoD, RpoN and FliA). Transcription of the RpoN-dependent genes
      requires the sensor kinase FlgS and response regulator FlgR. It is thought that
      FlgS senses some cellular cue to regulate transcription of the RpoN-dependent
      flagellar genes, but this signal has yet to be identified. Previous studies
      showed that transcription of the RpoN-dependent genes is inhibited by mutations
      in flhA, which encodes a membrane-bound component of the flagellar protein export
      apparatus. We found that depending on the H. pylori strain used, insertion
      mutations in flhA had different effects on expression of RpoN-dependent genes.
      Mutations in flhA in H. pylori strains B128 and ATCC 43504 (the type strain) were
      generated by inserting a chloramphenicol resistance cassette so as to effectively
      eliminate expression of the gene (DeltaflhA), or within the gene following codon
      77 (designated flhA77) or codon 454 (designated flhA454), which could allow
      expression of truncated FlhA proteins. All three flhA mutations severely
      inhibited transcription of the RpoN-dependent genes flaB and flgE in H. pylori
      B128. In contrast, levels of flaB and flgE transcripts in H. pylori ATCC 43504
      bearing either flhA77 or flhA454, but not DeltaflhA, were ~60 % of wild-type
      levels. The FlhA(454) variant was detected in membrane fractions prepared from H.
      pylori ATCC 43504 but not H. pylori B128, which may account for the phenotypic
      differences in the flhA mutations of the two strains. Taken together, these
      findings suggest that only the N-terminal region of FlhA is needed for
      transcription of the RpoN regulon. Interestingly, expression of an flaB'-'xylE
      reporter gene in H. pylori ATCC 43504 bearing the flhA77 allele was about
      eightfold higher than that of a strain with the wild-type allele, suggesting that
      expression of flaB is not only regulated at the level of transcription but also
      regulated post-transcriptionally.

PMID- 23154971
TI  - Purification and characterization of oxygen-inducible haem catalase from oxygen
      tolerant Bifidobacterium asteroides.
AB  - Bifidobacterium asteroides, originally isolated from honeybee intestine, was
      found to grow under 20% O(2) conditions in liquid shaking culture using MRS
      broth. Catalase activity was detected only in cells that were exposed to O(2) and
      grown in medium containing a haem source, and these cells showed higher viability
      on exposure to H(2)O(2). Passage through multiple column chromatography steps
      enabled purification of the active protein, which was identified as a homologue
      of haem catalase on the basis of its N-terminal sequence. The enzyme is a
      homodimer composed of a subunit with a molecular mass of 55 kDa, and the
      absorption spectrum shows the typical profile of bacterial haem catalase. A gene
      encoding haem catalase, which has an amino acid sequence coinciding with the N
      terminal amino acid sequence of the purified protein, was found in the draft
      genome sequence data of B. asteroides. Expression of the katA gene was induced in
      response to O(2) exposure. The haem catalase from B. asteroides shows about 70
      80% identity with those from lactobacilli and other lactic acid bacteria, and no
      homologues were found in other bifidobacterial genomes.

PMID- 23154972
TI  - Structural elucidation and genomic scrutiny of the C60-C100 mycolic acids of
      Segniliparus rotundus.
AB  - Mycolic acids, very long-chain alpha-alkyl, beta-hydroxylated fatty acids, occur
      in the members of the order Corynebacteriales where their chain lengths (C(26)
      C(88)) and structural features (oxygen functions, cis or trans double bonds,
      cyclopropane rings and methyl branches) are genus- and species-specific. The
      molecular composition and structures of the mycolic acids of two species
      belonging to the genus Segniliparus were determined by a combination of modern
      analytical chemical techniques, which include MS and NMR. They consist of mono
      ethylenic C(62-)C(64) (alpha'), di-ethylenic C(77)-C(79) (alpha) and extremely
      long-chain mycolic acids (alpha(+)) ranging from 92 to 98 carbon atoms and
      containing three unsaturations, cis and/or trans double bonds and/or
      cyclopropanes. The double bonds in each class of mycolic acids were positioned by
      oxidative cleavage and exhibit locations similar to those of alpha- and alpha'
      mycolic acids of mycobacteria. For the ultralong chain alpha-mycolic acids, the
      three double bonds were located at equally spaced carbon intervals (C(13)-C(16)),
      with the methyl branches adjacent to the proximal and distal trans double bonds.
      Examination of the Segniliparus rotundus genome compared with those of other
      members of the Corynebacteriales indicated two obvious differences in genes
      encoding the elongation fatty acid (FAS-II) enzymes involved in the biosynthesis
      of mycolic acids: the organization of 3-ketoacyl-ACP synthases (KasA and KasB)
      and (3R)-hydroxyacyl-ACP dehydratases (HadAB/BC), on one hand, and the presence
      of two copies of the hadB gene encoding the catalytic domain of the latter enzyme
      type, on the other. This observation is discussed in light of the most recent
      data accumulated on the biosynthesis of this hallmark of Corynebacteriales.

PMID- 23154973
TI  - Transcriptional regulation of the Rhodobacter capsulatus response regulator CtrA.
AB  - The Rhodobacter capsulatus response regulator CtrA controls the expression of 227
      genes, some of which are upregulated by both the phosphorylated and
      unphosphorylated forms of CtrA. Therefore, CtrA concentration alone, regardless
      of phosphorylation state, may determine expression of downstream genes, yet
      little is known about the regulation of ctrA in R. capsulatus. In this study we
      used a ctrA : : lacZ fusion plasmid to study the effects of medium composition,
      growth conditions and growth phase on R. capsulatus ctrA gene expression. These
      experiments indicate that ctrA expression is higher when cultures are grown in
      phototrophic (anaerobic) conditions compared with chemotrophic (aerobic)
      conditions, and is higher when grown in a minimal medium compared with a rich
      medium. We used several mutants to investigate possible regulatory pathways, and
      found that in R. capsulatus ctrA is not autoregulated but is regulated by a
      quorum-sensing system. The expression of ctrA increased as cell cultures moved
      through exponential phase and into stationary phase, with high levels of
      expression persisting long after culture turbidity plateaued. Although this
      growth phase-dependent pattern of expression was also observed in a quorum
      sensing mutant, the magnitude of ctrA expression was about 50% of the wild-type
      strain at all phases. Furthermore, reduction of phosphate concentration in the
      growth medium decreased ctrA expression in a culture density-independent manner,
      whereas reduction of malic acid (carbon source) or ammonium (nitrogen source)
      concentration had no effect. The regulation of ctrA expression in R. capsulatus
      appears to require the coordination of multiple pathways involved in detecting a
      variety of environmental conditions.

PMID- 23154974
TI  - Gamma-aminobutyric acid acts as a specific virulence regulator in Pseudomonas
      aeruginosa.
AB  - Gamma-aminobutyric acid (GABA) is widespread in the environment and can be used
      by animal and plants as a communication molecule. Pseudomonas species, in
      particular fluorescent ones, synthesize GABA and express GABA-binding proteins.
      In this study, we investigated the effects of GABA on the virulence of
      Pseudomonas aeruginosa. While exposure to GABA (10 uM) did not modify either the
      growth kinetics or the motility of the bacterium, its cytotoxicity and virulence
      were strongly increased. The Caenorhabditis elegans 'fast killing test' model
      revealed that GABA acts essentially through an increase in diffusible toxin(s).
      GABA also modulates the biofilm formation activity and adhesion properties of
      PAO1. GABA has no effect on cell surface polarity, biosurfactant secretion or on
      the lipopolysaccharide structure. The production of several exo-enzymes,
      pyoverdin and exotoxin A is not modified by GABA but we observed an increase in
      cyanogenesis which, by itself, could explain the effect of GABA on P. aeruginosa
      virulence. This mechanism appears to be regulated by quorum sensing. A proteomic
      analysis revealed that the effect of GABA on cyanogenesis is correlated with a
      reduction of oxygen accessibility and an over-expression of oxygen-scavenging
      proteins. GABA also promotes specific changes in the expression of thermostable
      and unstable elongation factors Tuf/Ts involved in the interaction of the
      bacterium with the host proteins. Taken together, these results suggest that GABA
      is a physiological regulator of P. aeruginosa virulence.

PMID- 23154976
TI  - Independent trafficking of the KCNQ1 K+ channel and H+-K+-ATPase in gastric
      parietal cells from mice.
AB  - Gastric acid secretion by the H(+)-K(+)-ATPase at the apical surface of activated
      parietal cells requires luminal K(+) provided by the KCNQ1/KCNE2 K(+) channel.
      However, little is known about the trafficking and relative spatial distribution
      of KCNQ1 and H(+)-K(+)-ATPase in resting and activated parietal cells and the
      capacity of KCNQ1 to control acid secretion. Here we show that inhibition of
      KCNQ1 activity quickly curtails gastric acid secretion in vivo, even when the
      H(+)-K(+)-ATPase is permanently anchored in the apical membrane, demonstrating a
      key role of the K(+) channel in controlling acid secretion. Three-dimensional
      imaging analysis of isolated mouse gastric units revealed that the majority of
      KCNQ1 resides in an intracytoplasmic, Rab11-positive compartment in resting
      parietal cells, distinct from H(+)-K(+)-ATPase-enriched tubulovesicles. Upon
      activation, there was a significant redistribution of H(+)-K(+)-ATPase and KCNQ1
      from intracytoplasmic compartments to the apical secretory canaliculi.
      Significantly, high Forster resonance energy transfer was detected between H(+)
      K(+)-ATPase and KCNQ1 in activated, but not resting, parietal cells. These
      findings demonstrate that H(+)-K(+)-ATPase and KCNQ1 reside in independent
      intracytoplasmic membrane compartments, or membrane domains, and upon activation
      of parietal cells, both membrane proteins are transported, possibly via Rab11
      positive recycling endosomes, to apical membranes, where the two molecules are
      closely physically opposed. In addition, these studies indicate that acid
      secretion is regulated by independent trafficking of KCNQ1 and H(+)-K(+)-ATPase.

PMID- 23154975
TI  - Smad7 inhibits autocrine expression of TGF-beta2 in intestinal epithelial cells
      in baboon necrotizing enterocolitis.
AB  - Preterm infants may be at risk of necrotizing enterocolitis (NEC) due to
      deficiency of transforming growth factor-beta 2 (TGF-beta(2)) in the developing
      intestine. We hypothesized that low epithelial TGF-beta(2) expression in preterm
      intestine and during NEC results from diminished autocrine induction of TGF
      beta(2) in these cells. Premature baboons delivered at 67% gestation were treated
      per current norms for human preterm infants. NEC was diagnosed by clinical and
      radiological findings. Inflammatory cytokines, TGF-beta(2), Smad7, Ski, and
      strawberry notch N (SnoN)/Ski-like oncoprotein (SKIL) was measured using
      quantitative reverse transcriptase-polymerase chain reaction, immunoblots, and
      immunohistochemistry. Smad7 effects were examined in transfected IEC6 intestinal
      epithelial cells in vitro. Findings were validated in archived human tissue
      samples of NEC. NEC was recorded in seven premature baboons. Consistent with
      existing human data, premature baboon intestine expressed less TGF-beta(2) than
      term intestine. TGF-beta(2) expression was regulated in epithelial cells in an
      autocrine fashion, which was interrupted in the premature intestine and during
      NEC due to increased expression of Smad7. LPS increased Smad7 binding to the TGF
      beta(2) promoter and was associated with dimethylation of the lysine H3K9, a
      marker of transcriptional silencing, on the nucleosome of TGF-beta(2). Increased
      Smad7 expression in preterm intestine was correlated with the deficiency of
      SnoN/SKIL, a repressor of the Smad7 promoter. Smad7 inhibits autocrine expression
      of TGF-beta(2) in intestinal epithelial cells in the normal premature intestine
      and during NEC. Increased Smad7 expression in the developing intestine may be due
      to a developmental deficiency of the SnoN/SKIL oncoprotein.

PMID- 23154977
TI  - Gastrokines: stomach-specific proteins with putative homeostatic and tumor
      suppressor roles.
AB  - During the past decade, a new family of stomach-specific proteins has been
      recognized. Known as "gastrokines" (GKNs), these secreted proteins are products
      of gastric mucus-producing cell lineages. GKNs are highly conserved in physical
      structure, and emerging data point to convergent functions in the modulation of
      gastric mucosal homeostasis and inflammation. While GKNs are highly prevalent in
      the normal stomach, frequent loss of GKN expression in gastric cancers, coupled
      with established antiproliferative activity, suggests putative tumor suppressor
      roles. Conversely, ectopic expression of GKNs in reparative lesions of Crohn's
      disease alludes to additional activity in epithelial wound healing and/or repair.
      Modes of action remain unsolved, but the recent demonstration of a GKN2-trefoil
      factor 1 heterodimer implicates functional interplay with trefoil factors. This
      review aims to provide a historical account of GKN biology and encapsulate the
      rapidly accumulating evidence supporting roles in gastric epithelial homeostasis
      and tumor suppression.

PMID- 23154978
TI  - Novel 3' ends that support translation.
AB  - The 3' ends of two large noncoding RNAs, MALAT1 (metastasis-associated lung
      adenocarcinoma transcript 1) and MEN beta, are formed by cleavage by RNase P and
      are capped but not polyadenylated. In the November 1, 2012, issue of Genes &
      Development, Wilusz and colleagues (pp. 2392-2407) show that when these 3' ends
      are formed on a GFP reporter, the resulting mRNA is exported to the cytoplasm and
      translated. The 3' end forms a novel triple-helical structure that supports
      export and translation as well as a poly(A) tail does.

PMID- 23154979
TI  - Spliceosome activation: U4 is the path, stem I is the goal, and Prp8 is the
      keeper. Let's cheer for the ATPase Brr2!
AB  - During pre-mRNA splicing, the spliceosome is activated for catalysis by unwinding
      base-paired U4/U6 small nuclear RNAs, a step that must be precisely timed. We
      know that unwinding requires the ATPase Brr2, but the mechanism and regulation of
      unwinding have been understood poorly. In the November 1, 2012, issue of Genes &
      Development, Hahn and colleagues (pp. 2408-2421) and Mozaffari-Jovin and
      colleagues (pp. 2422-2434) defined a pathway for U4/U6 unwinding. Moreover,
      Mozaffari-Jovin and colleagues suggested a mechanism for regulating Brr2.

PMID- 23154980
TI  - Zebrafish genetics gets the Scube on Hedgehog secretion.
AB  - Inspired by a zebrafish mutation, two recent studies by Creanga and colleagues
      (pp. 1312-1325) and Tukachinsky and colleagues have shed new light on the way in
      which lipidated Hedgehog proteins are secreted and released from expressing
      cells, suggesting a model for the sequential action of the Disp and Scube2
      proteins in this process.

PMID- 23154981
TI  - The SMAD2/3 corepressor SNON maintains pluripotency through selective repression
      of mesendodermal genes in human ES cells.
AB  - Activin/Nodal signaling via SMAD2/3 maintains human embryonic stem cell (hESC)
      pluripotency by direct transcriptional regulation of NANOG or, alternatively,
      induces mesoderm and definitive endoderm (DE) formation. In search of an
      explanation for these contrasting effects, we focused on SNON (SKIL), a potent
      SMAD2/3 corepressor that is expressed in hESCs but rapidly down-regulated upon
      differentiation. We show that SNON predominantly associates with SMAD2 at the
      promoters of primitive streak (PS) and early DE marker genes. Knockdown of SNON
      results in premature activation of PS and DE genes and loss of hESC morphology.
      In contrast, enforced SNON expression inhibits DE formation and diverts hESCs
      toward an extraembryonic fate. Thus, our findings provide novel mechanistic
      insight into how a single signaling pathway both regulates pluripotency and
      directs lineage commitment.

PMID- 23154982
TI  - Cell cycle gene-specific control of transcription has a critical role in
      proliferation of primordial germ cells.
AB  - Transcription elongation is stimulated by positive transcription elongation
      factor b (P-TEFb), for which activity is repressed in the 7SK small nuclear
      ribonucleoprotein (7SK snRNP) complex. We show here a critical role of 7SK snRNP
      in growth control of primordial germ cells (PGCs). The expression of p15(INK4b),
      a cyclin-dependent kinase inhibitor (CDKI) gene, in PGCs is selectively activated
      by P-TEFb and its recruiting molecule, Brd4, when the amount of active P-TEFb is
      increased due to reduction of the 7SK snRNP, and PGCs consequently undergo growth
      arrest. These results indicate that CDKI gene-specific control of transcription
      by 7SK snRNP plays a pivotal role in the maintenance of PGC proliferation.

PMID- 23154983
TI  - SEL-10/Fbw7-dependent negative feedback regulation of LIN-45/Braf signaling in C.
      elegans via a conserved phosphodegron.
AB  - The conserved E3 ubiquitin ligase component named SEL-10 in Caenorhabditis
      elegans and Fbw7 in mammals targets substrates for ubiquitin-mediated degradation
      through a high-affinity binding site called a Cdc4 phosphodegron (CPD). As many
      known substrates of Fbw7 are oncoproteins, the identification of new substrates
      may offer insight into cancer biology as well as aspects of proteome regulation.
      Here, we evaluated whether the presence of an evolutionarily conserved CPD would
      be a feasible complement to proteomics-based approaches for identifying new
      potential substrates. For functional assessments, we focused on LIN-45, a
      component of the signal transduction pathway underlying vulval induction and the
      ortholog of human Braf, an effector of Ras in numerous cancers. Our analysis
      demonstrates that LIN-45 behaves as a bona fide substrate of SEL-10, with
      mutation of the CPD or loss of sel-10 resulting in increased activity and protein
      stability in vivo. Furthermore, during vulval induction, the downstream kinase
      MPK-1/ERK is also required for LIN-45 protein degradation in a negative feedback
      loop, resulting in degradation of LIN-45 where ERK is highly active. As the CPD
      consensus sequence is conserved in human Braf, we propose that Fbw7 may also
      regulate Braf stability in some cell contexts. We discuss the implications of our
      findings for vulval development in C. elegans, the potential applicability to
      human Braf, and the value of a CPD-based predictive approach for human Fbw7
      substrates.

PMID- 23154984
TI  - CLOCK deubiquitylation by USP8 inhibits CLK/CYC transcription in Drosophila.
AB  - A conserved transcriptional feedback loop underlies animal circadian rhythms. In
      Drosophila, the transcription factors CLOCK (CLK) and CYCLE (CYC) activate the
      transcription of direct target genes like period (per) and timeless (tim). They
      encode the proteins PER and TIM, respectively, which repress CLK/CYC activity.
      Previous work indicates that repression is due to a direct PER-CLK/CYC
      interaction as well as CLK/CYC phosphorylation. We describe here the role of
      ubiquitin-specific protease 8 (USP8) in circadian transcriptional repression as
      well as the importance of CLK ubiquitylation in CLK/CYC transcription activity.
      usp8 loss of function (RNAi) or expression of a dominant-negative form of the
      protein (USP8-DN) enhances CLK/CYC transcriptional activity and alters fly
      locomotor activity rhythms. Clock protein and mRNA molecular oscillations are
      virtually absent within circadian neurons of USP8-DN flies. Furthermore, CLK
      ubiquitylation cycles robustly in wild-type flies and peaks coincident with
      maximal CLK/CYC transcription. As USP8 interacts with CLK and expression of USP8
      DN increases CLK ubiquitylation, the data indicate that USP8 deubiquitylates CLK,
      which down-regulates CLK/CYC transcriptional activity. Taken together with the
      facts that usp8 mRNA cycles and that its transcription is activated directly by
      CLK/CYC, USP8, like PER and TIM, contributes to the transcriptional feedback loop
      cycle that underlies circadian rhythms.

PMID- 23154985
TI  - Stable intronic sequence RNA (sisRNA), a new class of noncoding RNA from the
      oocyte nucleus of Xenopus tropicalis.
AB  - To compare nuclear and cytoplasmic RNA from a single cell type, free of cross
      contamination, we studied the oocyte of the frog Xenopus tropicalis, a giant cell
      with an equally giant nucleus. We isolated RNA from manually dissected nuclei and
      cytoplasm of mature oocytes and subjected it to deep sequencing. Cytoplasmic mRNA
      consisted primarily of spliced exons derived from ~6700 annotated genes. Nearly
      all of these genes were represented in the nucleus by intronic sequences.
      However, unspliced nascent transcripts were not detected. Inhibition of
      transcription or splicing for 1-2 d had little or no effect on the abundance of
      nuclear intronic sequences, demonstrating that they are unusually stable. RT-PCR
      analysis showed that these stable intronic sequences are transcribed from the
      coding strand and that a given intron can be processed into more than one
      molecule. Stable intronic sequence RNA (sisRNA) from the oocyte nucleus
      constitutes a new class of noncoding RNA. sisRNA is detectable by RT-PCR in
      samples of total RNA from embryos up to the mid-blastula stage, when zygotic
      transcription begins. Storage of sisRNA in the oocyte nucleus and its
      transmission to the developing embryo suggest that it may play important
      regulatory roles during oogenesis and/or early embryogenesis.

PMID- 23154986
TI  - Obstructive sleep apnoea and metabolic syndrome: put CPAP efficacy in a more
      realistic perspective.

PMID- 23154987
TI  - Prediction of peak flow values followed by feedback improves perception of lung
      function and adherence to inhaled corticosteroids in children with asthma.
AB  - BACKGROUND: Failure to detect respiratory compromise can lead to emergency
      healthcare use and fatal asthma attacks. The purpose of this study was to examine
      the effect of predicting peak expiratory flow (PEF) and receiving feedback on
      perception of pulmonary function and adherence to inhaled corticosteroids (ICS).
      METHODS: The sample consisted of 192 ethnic minority, inner-city children (100
      Puerto Rican, 54 African-American, 38 Afro-Caribbean) with asthma and their
      primary caregivers recruited from outpatient clinics in Bronx, New York.
      Children's PEF predictions were entered into an electronic spirometer and
      compared with actual PEF across 6 weeks. Children in one study were blinded to
      PEF (n=88; no feedback) and children in a separate study were able to see PEF
      (n=104; feedback) after predictions were locked in. Dosers were attached to
      asthma medications to monitor use. RESULTS: Children in the feedback condition
      displayed greater accuracy (p<0.001), less under-perception (p<0.001) and greater
      over-perception (p<0.001) of respiratory compromise than children in the no
      feedback condition. This between-group difference was evident soon after baseline
      training and maintained across 6 weeks. The feedback condition displayed greater
      adherence to ICS (p<0.01) and greater quick-relief medication use (p<0.01) than
      the no feedback condition. CONCLUSIONS: Feedback on PEF predictions for ethnic
      minority, inner-city children may decrease under-perception of respiratory
      compromise and increase adherence to controller medications. Children and their
      families may shift their attention to asthma perception and management as a
      result of this intervention.

PMID- 23154988
TI  - Your asthma reliever inhaler: never leave home without it.

PMID- 23154989
TI  - Heterotopic ossification encasing a plombage cavity.

PMID- 23154990
TI  - A novel antibody for human induced pluripotent stem cells and embryonic stem
      cells recognizes a type of keratan sulfate lacking oversulfated structures.
AB  - We have generated a monoclonal antibody (R-10G) specific to human induced
      pluripotent stem (hiPS)/embryonic stem (hES) cells by using hiPS cells (Tic) as
      an antigen, followed by differential screening of mouse hybridomas with hiPS and
      human embryonal carcinoma (hEC) cells. Upon western blotting with R-10G, hiPS/ES
      cell lysates gave a single but an unusually diffuse band at a position
      corresponding to >250 kDa. The antigen protein was isolated from the induced
      pluripotent stem (iPS) cell lysates with an affinity column of R-10G. The R-10G
      positive band was resistant to digestion with peptide N-glycanase F (PNGase F),
      neuraminidase, fucosidase, chondrotinase ABC and heparinase mix, but it
      disappeared almost completely on digestion with keratanase, keratanase II and
      endo-beta-galactosidase, indicating that the R-10G epitope is a keratan sulfate.
      The carrier protein of the R-10G epitope was identified as podocalyxin by liquid
      chromatography/mass spectrometry (LC/MS/MS) analysis of the R-10G positive
      protein band material obtained on sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis (SDS-PAGE). The R-10G epitope is a type of keratan sulfate with
      some unique properties. (1) The epitope is expressed only on hiPS/ES cells, i.e.
      not on hEC cells, unlike those recognized by the conventional hiPS/ES marker
      antibodies. (2) The epitope is a type of keratan sulfate lacking oversulfated
      structures and is not immunologically cross-reactive with high-sulfated keratan
      sulfate. (3) The R-10G epitope is distributed heterogeneously on hiPS cells,
      suggesting that a single colony of undifferentiated hiPS cells consists of
      different cell subtypes. Thus, R-10G is a novel antibody recognizing hiPS/ES
      cells, and should be a new molecular probe for disclosing the roles of glycans on
      these cells.

PMID- 23154991
TI  - A comparison of exercise type and intensity on the noninvasive assessment of
      skeletal muscle mitochondrial function using near-infrared spectroscopy.
AB  - Near-infrared spectroscopy (NIRS) can be used to measure muscle oxygen
      consumption (mVO(2)) using arterial occlusions. The recovery rate of mVO(2) after
      exercise can provide an index of skeletal muscle mitochondrial function. The
      purpose of this study was to test the influence of exercise modality and
      intensity on NIRS measurements of mitochondrial function. Three experiments were
      performed. Thirty subjects (age: 18-27 yr) were tested. NIRS signals were
      corrected for blood volume changes. The recovery of mVO(2) after exercise was fit
      to a monoexponential curve, and a rate constant was calculated (directly related
      to mitochondrial function). No differences were found in NIRS rate constants for
      VOL and ES exercises (2.04 +/- 0.57 vs. 2.01 +/- 0.59 min(-1) for VOL and ES,
      respectively; P = 0.317). NIRS rate constants were independent of the contraction
      frequency for both VOL and ES (VOL: P = 0.166 and ES: P = 0.780). ES current
      intensity resulted in significant changes to the normalized time-tension integral
      (54 +/- 11, 82 +/- 7, and 100 +/- 0% for low, medium, and high currents,
      respectively; P < 0.001) but did not influence NIRS rate constants (2.02 +/-
      0.54, 1.95 +/- 0.44, 2.02 +/- 0.46 min(-1) for low, medium, and high currents,
      respectively; P = 0.771). In summary, NIRS measurements of skeletal muscle
      mitochondrial function can be compared between VOL and ES exercises and were
      independent of the intensity of exercise. NIRS represents an important new
      technique that is practical for testing in research and clinical settings.

PMID- 23154992
TI  - Sex differences in postsynaptic sweating and cutaneous vasodilation.
AB  - The current study aimed to determine whether a peripheral modulation of sweating
      contributes to the lower sudomotor thermosensitivity previously observed in
      females during exercise. We examined dose-response relationships in 12 males and
      12 females to incremental doses of acetylcholine (ACh) and methylcholine (MCh)
      for sweating (ventilated capsule), as well as to ACh and sodium nitroprusside
      (SNP) for cutaneous vasodilation (laser-Doppler). All drugs were infused using
      intradermal microdialysis. On a separate day, potential sex differences in the
      onset threshold and/or thermosensitivity of heat loss responses were assessed
      during progressive increases in mean body temperature elicited by passive
      heating. Increases in sweating as a function of increasing concentration of ACh
      (P = 0.008) and MCh (P = 0.046) significantly differed between males and females.
      Although the concentration eliciting 50% of the maximal sweating response did not
      differ between sexes for either agonist (P > 0.1), maximum values were lower in
      females in response to ACh (0.34 +/- 0.12 vs. 0.59 +/- 0.19 mg.min(-1).cm(-2), P
      = 0.04) and MCh (0.48 +/- 0.12 vs. 0.78 +/- 0.26 mg.min(-1).cm(-2), P = 0.05).
      This observation was paralleled by a lower thermosensitivity of sudomotor
      activity in females during passive heating (1.29 +/- 0.34 vs. 1.83 +/- 0.33
      mg.min(-1).cm(-2). degrees C(-1), P = 0.03), with no significant differences in
      the change in mean body temperature at which onset of sweating occurred (0.85 +/-
      0.19 vs. 0.67 +/- 0.13 degrees C, P = 0.10). No sex differences in cutaneous
      vasodilation were observed in response to ACh and SNP, as well as during passive
      heating (all P > 0.1). These findings provide direct evidence for a peripheral
      modulation of sudomotor activity in females. In contrast, sex does not modulate
      cutaneous vasodilation.

PMID- 23154993
TI  - Vasoconstrictor responsiveness during hyperbaric hyperoxia in contracting human
      muscle.
AB  - Large increases in systemic oxygen content cause substantial reductions in
      exercising forearm blood flow (FBF) due to increased vascular resistance. We
      hypothesized that 1) functional sympatholysis (blunting of sympathetic alpha
      adrenergic vasoconstriction) would be attenuated during hyperoxic exercise and 2)
      alpha-adrenergic blockade would limit vasoconstriction during hyperoxia and
      increase FBF to levels observed under normoxic conditions. Nine male subjects
      (age 28 +/- 1 yr) performed forearm exercise (20% of maximum) under normoxic and
      hyperoxic conditions. Studies were performed in a hyperbaric chamber at 1
      atmosphere absolute (ATA; sea level) while breathing 21% O(2) and at 2.82 ATA
      while breathing 100% O(2) (estimated change in arterial O(2) content ~6 ml
      O(2)/100 ml). FBF (ml/min) was measured using Doppler ultrasound. Forearm
      vascular conductance (FVC) was calculated from FBF and blood pressure (arterial
      catheter). Vasoconstrictor responsiveness was determined using intra-arterial
      tyramine. FBF and FVC were substantially lower during hyperoxic exercise than
      normoxic exercise (~20-25%; P < 0.01). At rest, vasoconstriction to tyramine (%
      decrease from pretyramine values) did not differ between normoxia and hyperoxia
      (P > 0.05). During exercise, vasoconstrictor responsiveness was slightly greater
      during hyperoxia than normoxia (-22 +/- 3 vs. -17 +/- 2%; P < 0.05). However,
      during alpha-adrenergic blockade, hyperoxic exercise FBF and FVC remained lower
      than during normoxia (P < 0.01). Therefore, our data suggest that although the
      vasoconstrictor responsiveness during hyperoxic exercise was slightly greater, it
      likely does not explain the majority of the large reductions in FBF and FVC (~20
      25%) during hyperbaric hyperoxic exercise.

PMID- 23154994
TI  - The timing of administration of a clinically relevant dose of losartan influences
      the healing process after contusion induced muscle injury.
AB  - Losartan (Los) is a Food and Drug Administration-approved antihypertensive
      medication that has a well-tolerated side effect profile. We have demonstrated
      that treatment with Los immediately after injury was effective at promoting
      muscle healing and inducing an antifibrotic effect in a murine model of skeletal
      muscle injury. We initially investigated the minimum effective dose of Los
      administration immediately after injury and subsequently determined whether the
      timing of administering a clinically relevant dose of Los would influence its
      effectiveness at improving muscle healing after muscle injury. In the first part
      of this study, mice were administered 3, 10, 30, or 300 mg.kg(-1).day(-1) of Los
      immediately after injury, and the healing process was evaluated histologically
      and physiologically 4 wk after injury. In the second study, the clinically
      relevant dose of 10 mg.kg(-1).day(-1) was administered immediately or started at
      3 or 7 days postinjury. The administration of 300 mg.kg(-1).day(-1) immediately
      following injury led to a significant increase in muscle regeneration, a
      significant decrease in fibrosis, and an improvement in muscle function.
      Moreover, we observed a significant decrease in fibrosis and a significant
      increase in muscle regeneration at 4 wk postinjury, when the clinically relevant
      dose of 10 mg.kg(-1).day(-1) was administered at 3 or 7 days postinjury.
      Functional evaluation also demonstrated a significant improvement compared with
      the injured untreated control when Los treatment was initiated 3 days after
      injury. Our study revealed accelerated muscle healing when the 300 mg.kg(-1).day(
      1) of Los was administered immediately after injury and a clinically relevant
      dose of 10 mg.kg(-1).day(-1) of Los was administered at 3 or 7 days postinjury.

PMID- 23154995
TI  - The effect of hypoxemia and exercise on acute mountain sickness symptoms.
AB  - Performing exercise during the first hours of hypoxic exposure is thought to
      exacerbate acute mountain sickness (AMS), but whether this is due to increased
      hypoxemia or other mechanisms associated with exercise remains unclear. In 12
      healthy men, AMS symptoms were assessed during three 11-h experimental sessions:
      1) in Hypoxia-exercise, inspiratory O(2) fraction (Fi(O(2))) was 0.12, and
      subjects performed 4-h cycling at 45% Fi(O(2))-specific maximal power output from
      the 4th to the 8th hour; 2) in Hypoxia-rest, Fi(O(2)) was continuously adjusted
      to match the same arterial oxygen saturation as in Hypoxia-exercise, and subjects
      remained at rest; and 3) in Normoxia-exercise, Fi(O(2)) was 0.21, and subjects
      cycled as in Hypoxia-exercise at 45% Fi(O(2))-specific maximal power output. AMS
      scores did not differ significantly between Hypoxia-exercise and Hypoxia-rest,
      while they were significantly lower in Normoxia-exercise (Lake Louise score: 5.5
      +/- 2.1, 4.4 +/- 2.4, and 2.3 +/- 1.5, and cerebral Environmental Symptom
      Questionnaire: 1.2 +/- 0.7, 1.0 +/- 1.0, and 0.3 +/- 0.4, in Hypoxia-exercise,
      Hypoxia-rest, and Normoxia-exercise, respectively; P < 0.01). Headache scored by
      visual analog scale was higher in Hypoxia-exercise and Hypoxia-rest compared with
      Normoxia-exercise (36 +/- 22, 35 +/- 25, and 5 +/- 6, P < 0.001), while the
      perception of fatigue was higher in Hypoxia-exercise compared with Hypoxia-rest
      (60 +/- 24, 32 +/- 22, and 46 +/- 23, in Hypoxia-exercise, Hypoxia-rest, and
      Normoxia-exercise, respectively; P < 0.01). Despite significant physiological
      stress during hypoxic exercise and some AMS symptoms induced by normoxic cycling
      at similar relative workload, exercise does not significantly worsen AMS severity
      during the first hours of hypoxic exposure at a given arterial oxygen
      desaturation. Hypoxemia per se appears, therefore, to be the main mechanism
      underlying AMS, whether or not exercise is performed.

PMID- 23154997
TI  - A survey of primary care doctors in ten countries shows progress in use of health
      information technology, less in other areas.
AB  - Health reforms in high-income countries increasingly aim to redesign primary care
      to improve the health of the population and the quality of health care services,
      and to address rising costs. Primary care improvements aim to provide patients
      with better access to care and develop more-integrated care systems through
      better communication and teamwork across sites of care, supported by health
      information technology and feedback to physicians on their performance. Our
      international survey of primary care doctors in Australia, Canada, France,
      Germany, the Netherlands, New Zealand, Norway, Switzerland, the United Kingdom,
      and the United States found progress in the use of health information technology
      in health care practices, particularly in the United States. Yet a high
      percentage of primary care physicians in all ten countries reported that they did
      not routinely receive timely information from specialists or hospitals. Countries
      also varied notably in the extent to which physicians received information on
      their own performance. In terms of access, US doctors were the most likely to
      report that they spent substantial time grappling with insurance restrictions and
      that their patients often went without care because of costs. Signaling the need
      for reforms, the vast majority of US doctors surveyed said that the health care
      system needs fundamental change.

PMID- 23154996
TI  - Cardiac mechanics are impaired during fatiguing exercise and cold pressor test in
      healthy older adults.
AB  - We sought to determine how the aging left ventricle (LV) responds to sympathetic
      nervous system (SNS) activation. Three separate echocardiographic experiments
      were conducted in 11 healthy young (26 +/- 1 yr) and 11 healthy older (64 +/- 1
      yr) adults. Tissue Doppler imaging was used to measure systolic myocardial
      velocity (S(m)), early diastolic myocardial velocity (E(m)), and late diastolic
      myocardial velocity (A(m)) during isometric fatiguing handgrip (IFHG), a 2-min
      cold pressor test (CPT), and 5 min of normobaric hypoxia. Heart rate (HR) and
      mean arterial pressure (MAP) were also monitored on a beat-by-beat basis; rate
      pressure product (RPP) was used as an index of myocardial oxygen demand. At peak
      IFHG, the groups had similar increases in RPP, but the DeltaS(m) was
      significantly greater (i.e., larger impairment) in the older subjects (-0.82 +/-
      0.13 cm/s) compared with the young subjects (0.37 +/- 0.30 cm/s). At peak IFHG,
      the DeltaE(m) was similar between older (-1.59 +/- 0.68 cm/s) and young subjects
      (-1.06 +/- 0.76 cm/s). In response to the CPT, both S(m) and E(m) were reduced in
      the older adults but did not change relative to baseline in the young subjects.
      Normobaric hypoxia elevated HR and RPP in both groups but did not alter Tissue
      Doppler parameters. These data indicate that S(m) and E(m) are reduced in healthy
      older adults during IFHG and CPT. We speculate that suboptimal LV adaptations to
      SNS stress may partly explain why acute heavy exertion can trigger myocardial
      ischemia.

PMID- 23154998
TI  - A mixed-method examination of food marketing directed towards children in
      Australian supermarkets.
AB  - The purpose of this study was to determine the prevalence of children's food
      requests, and parents' experiences of food marketing directed towards children,
      in the supermarket environment. A mixed-method design was used. Firstly,
      intercept interviews were conducted with parents accompanied by a child/children
      on exiting supermarkets (sampled from a large regional centre in Australia).
      Parents were asked about the prevalence and types of food requests by
      child/children during their supermarket visit and whether they purchased these
      foods. Secondly, focus groups (n = 13) and telephone interviews (n = 3) were
      conducted exploring parents' experiences of supermarket shopping with children
      and the impact of child-directed marketing. Of the 158 intercept survey
      participants (30% response rate), 73% reported a food request during the
      supermarket visit. Most requested food items (88%) were unhealthy foods, with
      chocolate/confectionery being the most common food category requested (40%). Most
      parents (70%) purchased at least one food item requested during the shopping
      trip. Qualitative interviews identified four themes associated with food requests
      and prompts in the supermarket: parents' experience of pester power in the
      supermarket; prompts for food requests in the supermarket; parental responses to
      pestering in the supermarket environment, and; strategies to manage pestering and
      minimize requests for food items. Food requests from children are common during
      supermarket shopping. Despite the majority of the requests being unhealthy,
      parents often purchase these foods. Parents reported difficulties dealing with
      constant requests and expressed desire for environmental changes including
      confectionery-free checkouts, minimization of child friendly product placement
      and reducing children's exposure to food marketing. 

PMID- 23154999
TI  - The HSP90 inhibitor geldanamycin perturbs endosomal structure and drives
      recycling ErbB2 and transferrin to modified MVBs/lysosomal compartments.
AB  - The ErbB2 receptor is a clinically validated cancer target whose internalization
      and trafficking mechanisms remain poorly understood. HSP90 inhibitors, such as
      geldanamycin (GA), have been developed to target the receptor to degradation or
      to modulate downstream signaling. Despite intense investigations, the entry route
      and postendocytic sorting of ErbB2 upon GA stimulation have remained
      controversial. We report that ErbB2 levels inversely impact cell clathrin
      mediated endocytosis (CME) capacity. Indeed, the high levels of the receptor are
      responsible for its own low internalization rate. GA treatment does not directly
      modulate ErbB2 CME rate but it affects ErbB2 recycling fate, routing the receptor
      to modified multivesicular endosomes (MVBs) and lysosomal compartments, by
      perturbing early/recycling endosome structure and sorting capacity. This activity
      occurs irrespective of the cargo interaction with HSP90, as both ErbB2 and the
      constitutively recycled, HSP90-independent, transferrin receptor are found within
      modified endosomes, and within aberrant, elongated recycling tubules, leading to
      modified MVBs/lysosomes. We propose that GA, as part of its anticancer activity,
      perturbs early/recycling endosome sorting, routing recycling cargoes toward mixed
      endosomal compartments.

PMID- 23155000
TI  - Small heat shock proteins target mutant cystic fibrosis transmembrane conductance
      regulator for degradation via a small ubiquitin-like modifier-dependent pathway.
AB  - Small heat shock proteins (sHsps) bind destabilized proteins during cell stress
      and disease, but their physiological functions are less clear. We evaluated the
      impact of Hsp27, an sHsp expressed in airway epithelial cells, on the common
      protein misfolding mutant that is responsible for most cystic fibrosis. F508del
      cystic fibrosis transmembrane conductance regulator (CFTR), a well-studied
      protein that is subject to cytosolic quality control, selectively associated with
      Hsp27, whose overexpression preferentially targeted mutant CFTR to proteasomal
      degradation. Hsp27 interacted physically with Ubc9, the small ubiquitin-like
      modifier (SUMO) E2 conjugating enzyme, implying that F508del SUMOylation leads to
      its sHsp-mediated degradation. Enhancing or disabling the SUMO pathway increased
      or blocked Hsp27's ability to degrade mutant CFTR. Hsp27 promoted selective
      SUMOylation of F508del NBD1 in vitro and of full-length F508del CFTR in vivo,
      which preferred endogenous SUMO-2/3 paralogues that form poly-chains. The SUMO
      targeted ubiquitin ligase (STUbL) RNF4 recognizes poly-SUMO chains to facilitate
      nuclear protein degradation. RNF4 overexpression elicited F508del degradation,
      whereas Hsp27 knockdown blocked RNF4's impact on mutant CFTR. Similarly, the
      ability of Hsp27 to degrade F508del CFTR was lost during overexpression of
      dominant-negative RNF4. These findings link sHsp-mediated F508del CFTR
      degradation to its SUMOylation and to STUbL-mediated targeting to the ubiquitin
      proteasome system and thereby implicate this pathway in the disposal of an
      integral membrane protein.

PMID- 23155001
TI  - Competitive binding of CUGBP1 and HuR to occludin mRNA controls its translation
      and modulates epithelial barrier function.
AB  - RNA-binding proteins CUG-binding protein 1 (CUGBP1) and HuR are highly expressed
      in epithelial tissues and modulate the stability and translation of target mRNAs.
      Here we present evidence that CUGBP1 and HuR jointly regulate the translation of
      occludin and play a crucial role in the maintenance of tight junction (TJ)
      integrity in the intestinal epithelial cell monolayer. CUGBP1 and HuR competed
      for association with the same occludin 3'-untranslated region element and
      regulated occludin translation competitively and in opposite directions. CUGBP1
      overexpression decreased HuR binding to occludin mRNA, repressed occludin
      translation, and compromised the TJ barrier function, whereas HuR overexpression
      inhibited CUGBP1 association with occludin mRNA and promoted occludin
      translation, thereby enhancing the barrier integrity. Repression of occludin
      translation by CUGBP1 was due to the colocalization of CUGBP1 and tagged occludin
      RNA in processing bodies (P-bodies), and this colocalization was prevented by HuR
      overexpression. These findings indicate that CUGBP1 represses occludin
      translation by increasing occludin mRNA recruitment to P-bodies, whereas HuR
      promotes occludin translation by blocking occludin mRNA translocation to P-bodies
      via the displacement of CUGBP1.

PMID- 23155002
TI  - SmgGDS antagonizes BPGAP1-induced Ras/ERK activation and neuritogenesis in PC12
      cell differentiation.
AB  - BPGAP1 is a Rho GTPase-activating protein (RhoGAP) that regulates cell
      morphogenesis, cell migration, and ERK signaling by the concerted action of its
      proline-rich region (PRR), RhoGAP domain, and the BNIP-2 and Cdc42GAP homology
      (BCH) domain. Although multiple cellular targets for the PRR and RhoGAP have been
      identified, and their functions delineated, the mechanism by which the BCH domain
      regulates functions of BPGAP1 remains unclear. Here we show that its BCH domain
      induced robust ERK activation leading to PC12 cell differentiation by targeting
      specifically to K-Ras. Such stimulatory effect was inhibited, however, by both
      dominant-negative mutants of Mek2 (Mek2-K101A) and K-Ras (K-Ras-S17N) and also by
      the small G-protein GDP dissociation stimulator (SmgGDS). Consequently SmgGDS
      knockdown released this inhibition and resulted in a superinduction of K-Ras
      activation and PC12 differentiation mediated by BCH domain. These results
      demonstrate the versatility of the BCH domain of BPGAP1 in regulating ERK
      signaling by involving K-Ras and SmgGDS and support the unique role of BPGAP1 as
      a dual regulator for Ras and Rho signaling in cell morphogenesis and
      differentiation.

PMID- 23155004
TI  - Inferring population histories using genome-wide allele frequency data.
AB  - The recent development of high-throughput genotyping technologies has
      revolutionized the collection of data in a wide range of both model and nonmodel
      species. These data generally contain huge amounts of information about the
      demographic history of populations. In this study, we introduce a new method to
      estimate divergence times on a diffusion time scale from large single-nucleotide
      polymorphism (SNP) data sets, conditionally on a population history that is
      represented as a tree. We further assume that all the observed polymorphisms
      originate from the most ancestral (root) population; that is, we neglect
      mutations that occur after the split of the most ancestral population. This
      method relies on a hierarchical Bayesian model, based on Kimura's time-dependent
      diffusion approximation of genetic drift. We implemented a Metropolis-Hastings
      within Gibbs sampler to estimate the posterior distribution of the parameters of
      interest in this model, which we refer to as the Kimura model. Evaluating the
      Kimura model on simulated population histories, we found that it provides
      accurate estimates of divergence time. Assessing model fit using the deviance
      information criterion (DIC) proved efficient for retrieving the correct tree
      topology among a set of competing histories. We show that this procedure is
      robust to low-to-moderate gene flow, as well as to ascertainment bias, providing
      that the most distantly related populations are represented in the discovery
      panel. As an illustrative example, we finally analyzed published human data
      consisting in genotypes for 452,198 SNPs from individuals belonging to four
      populations worldwide. Our results suggest that the Kimura model may be helpful
      to characterize the demographic history of differentiated populations, using
      genome-wide allele frequency data.

PMID- 23155003
TI  - Ancient properties of spider silks revealed by the complete gene sequence of the
      prey-wrapping silk protein (AcSp1).
AB  - Spider silk fibers have impressive mechanical properties and are primarily
      composed of highly repetitive structural proteins (termed spidroins) encoded by a
      single gene family. Most characterized spidroin genes are incompletely known
      because of their extreme size (typically >9 kb) and repetitiveness, limiting
      understanding of the evolutionary processes that gave rise to their unusual gene
      architectures. The only complete spidroin genes characterized thus far form the
      dragline in the Western black widow, Latrodectus hesperus. Here, we describe the
      first complete gene sequence encoding the aciniform spidroin AcSp1, the primary
      component of spider prey-wrapping fibers. L. hesperus AcSp1 contains a single
      enormous (~19 kb) exon. The AcSp1 repeat sequence is exceptionally conserved
      between two widow species (~94% identity) and between widows and distantly
      related orb-weavers (~30% identity), consistent with a history of strong
      purifying selection on its amino acid sequence. Furthermore, the 16 repeats (each
      371-375 amino acids long) found in black widow AcSp1 are, on average, >99%
      identical at the nucleotide level. A combination of stabilizing selection on
      amino acid sequence, selection on silent sites, and intragenic recombination
      likely explains the extreme homogenization of AcSp1 repeats. In addition,
      phylogenetic analyses of spidroin paralogs support a gene duplication event
      occurring concomitantly with specialization of the aciniform glands and the
      tubuliform glands, which synthesize egg-case silk. With repeats that are
      dramatically different in length and amino acid composition from dragline
      spidroins, our L. hesperus AcSp1 expands the knowledge base for developing silk
      based biomimetic technologies.

PMID- 23155006
TI  - Characterization of Staphylococcus xylosus isolated from broiler chicken barn
      bioaerosol.
AB  - In this study we isolated and characterized Staphylococcus xylosus, a coagulase
      negative staphylococcal species considered as commensal and one of the prevalent
      staphylococcal species found in poultry bioaerosol. Isolates were obtained using
      air samplers and selective phenylethyl alcohol agar for gram-positive bacteria
      during 35-d periods at different times of the day. A total of 200 colonies were
      recovered and after basic biochemical tests were performed, presumptive
      staphylococci were subsequently identified by API Staph strips. A total of 153
      (76.5%) staphylococci were found, among which 84 were S. xylosus (46 and 38
      isolated inside and outside, respectively). Biofilm formation was observed in
      86.9% of S. xylosus isolates, whereas 79.8% of them showed hemolytic activity.
      There was a strong correlation (92.5%) between biofilm formation and hemolytic
      activity. All 84 S. xylosus isolates were susceptible to amikacin,
      ampicillin/sulbactam, chloramphenicol, ciprofloxacin, gentamycin, kanamycin,
      linezolid, trimethoprim/sulfamethoxazole, and vancomycin. Resistance to nalidixic
      acid (86.9%), novobiocin (85.7%), penicillin (70.2%), lincomycin (46.4%),
      oxacillin (42.9%), ampicillin (27.4%), tetracycline (21.4%), erythromycin
      (11.9%), bacitracin (10.7%), and streptomycin (2.4%) was observed among the
      isolates. Resistance to tetracycline, lincomycin, erythromycin, and beta-lactam
      antibiotics was occasionally linked to the tetK, linA, ermB, and blaZ genes,
      respectively. Random amplification of polymorphic DNA results showed similarity
      of 15 to 99% between isolates collected outside and inside the barn, indicating
      genetic diversity of these isolates. Our study indicates that characterization of
      poultry bioaerosol coagulase-negative staphylococcal species such as S. xylosus
      is necessary for assessing their safety status for both poultry and humans.

PMID- 23155005
TI  - Functional evolution of an anthocyanin pathway enzyme during a flower color
      transition.
AB  - Dissecting the genetic basis for the evolution of species differences requires a
      combination of phylogenetic and molecular genetic perspectives. By mapping the
      genetic changes and their phenotypic effects onto the phylogeny, it is possible
      to distinguish changes that may have been directly responsible for a new
      character state from those that fine tune the transition. Here, we use
      phylogenetic and functional methods to trace the evolution of substrate
      specificity in dihydroflavonol-4-reductase (Dfr), an anthocyanin pathway gene
      known to be involved in the transition from blue to red flowers in Iochroma.
      Ancestral state reconstruction indicates that three substitutions occurred during
      the flower color transition, whereas several additional substitutions followed
      the transition. Comparisons of enzymatic function between ancestral proteins in
      blue- and red-flowered lineages and proteins from present-day taxa demonstrate
      that evolution of specificity for red pigment precursors was caused by the first
      three substitutions, which were fixed by positive selection and which differ from
      previously documented mutations affecting specificity. Two inferred substitutions
      subsequent to the initial flower color transition were also adaptive and resulted
      in an additional increase in specificity for red precursors. Epistatic
      interactions among both sets of substitutions may have limited the order of
      substitutions along branches of the phylogeny leading from blue-pigmented
      ancestors to the present-day red-flowered taxa. These results suggest that the
      species differences in DFR specificity may arise by a combination of selection on
      flower color and selection for improved pathway efficiency but that the exact
      series of genetic changes resulting in the evolution of specificity is likely to
      be highly contingent on the starting state.

PMID- 23155007
TI  - Effect of combinations of monochromatic lights on growth and productive
      performance of broilers.
AB  - Our previous study suggested that green light promotes broiler growth during the
      early stage [posthatching day (P) 0 to P26], and blue light enhances growth
      during the later stage (P27 to P49). The purpose of this study was to improve
      broiler growth and productive performance by using a combination of monochromatic
      lights at critical points between the early and later stages of growth. A total
      of 512 male Arbor Acres broilers on P0 were reared under white light (W), red
      light (R), green light (G), and blue light (B) by using light-emitting diode
      lamps at 15 +/- 0.2 lx from P0 to P26 (16 replicate pens/group, 8 birds/pen), and
      then switching to another color of light until P49 (4 replicate pens/group, 8
      birds/pen). As compared with single monochromatic lights, broilers reared in
      environments under combinations of monochromatic lights, W->G, R->B, G->B, and B
      >G, attained heavier BW than those reared in environments under W->W (3.18 to
      12.00%), R->R (1.96 to 18.14%), G->G (0.85 to 5.08%), and B->B (0.39 to 4.70%),
      respectively. In addition, feed conversion ratios in the W->B, R->B, and G->B
      combinations were lower than feed conversion ratios for W->W (15.86%, P < 0.05),
      R->R (18.41%, P < 0.05), and G->G (3.37%), respectively. Moreover, the
      eviscerated carcass weight and breast, thigh, and crus muscle weights under G->B
      were greater by 0.40 to 56.23% than were those for the other light groups except
      W->B (eviscerated carcass) and B->G (breast muscle). The results suggest that the
      application of the G->B and B->G exchanges can be used successfully to improve
      growth and productive performance in broilers.

PMID- 23155008
TI  - Associations of chicken Mx1 polymorphism with antiviral responses in avian
      influenza virus infected embryos and broilers.
AB  - Avian influenza virus (AIV) is a major respiratory disease of poultry that causes
      catastrophic losses to the poultry industry. The Mx protein has been shown to
      confer antiviral responses to influenza viruses in mice. One nonsynonymous
      substitution (S631N) in the chicken Mx protein is reported to be associated with
      resistance to AIV infection in vitro. The previous studies suggested controversy
      over whether this substitution in the Mx protein plays an important antiviral
      role in AIV infection in the chicken. It would be intriguing to investigate if
      the substitution is associated with resistance to AIV infection both in ovo and
      in vivo in chickens. In this study, the embryos and young chicks were generated
      from the cross of Mx1 heterozygous (S631N) parents with an expected segregating
      ratio of 1:2:1 in the progeny. A PCR length polymorphism was developed to
      genotype the Mx1 gene from 119 embryos and 48 chickens. The embryonated chicken
      eggs were inoculated with 10(6) 50% embryo infectious dose (EID(50)) H5N9 AIV on
      d 13. Hemagglutinating units in allantoic fluid were determined at 48 h
      postinoculation. For the in vivo study, twenty-four 1-wk-old broilers were
      inoculated with 10(6) EID(50) H5N3, and virus titers in lungs were evaluated at d
      4 postinoculation. This is the first report revealing no significant association
      between Mx1 genotypes and low pathogenesis AIV infection both in ovo and in vivo
      in the chicken. Total RNA samples were isolated from chicken lung tissues in the
      in vivo study, and the Mx1 mRNA expression assay among 3 genotypes also suggested
      that only heterozygote birds had significantly greater expression with AIV
      infection than noninfected birds. A recombination breakpoint within Mx1 gene was
      also first identified, which has laid a solid foundation for further
      understanding biological function of the Mx1 gene in chickens. The current study
      provides valuable information on the effect of the Mx1 gene on the genetic
      resistance to AIV in chickens, and Mx1 will not be applicable for enhancing
      genetic resistance to AIV infection in chickens.

PMID- 23155009
TI  - Egg quality traits differ in hens selected for high as compared with low antibody
      response to sheep red blood cells.
AB  - White Leghorn chickens were selected for 36 generations for high (HAS) or low
      (LAS) antibody response to SRBC 5 d after an intravenous challenge. Our objective
      was to determine differences in egg quality resulting from that selection. In
      total, eggs from 45 hens from each line were assessed for shape index (SI),
      weight (WT, g), albumen height (AH, mm), Haugh units (HU), yolk color (YC), and
      eggshell weight (ESW, g) and thickness (EST, mm). Three cycles representing
      early, middle, and late stages of production were examined. Eggs from HAS hens
      had higher SI scores (4.12 +/- 0.55; P < 0.001) and greater AH (0.27 +/- 0.12; P
      < 0.001) and HU (1.89 +/- 0.91; P = 0.04) than LAS hens; conversely, eggs from
      LAS hens had greater EST (0.03 +/- 0.01 g; P < 0.001) and heavier ESW (0.66 +/-
      0.09 g; P < 0.001) than HAS hens. Lines were similar for WT and YC (P > 0.52).
      Albumen height and HU decreased (P < 0.001), whereas WT, ESW, and EST increased
      (P < 0.001) over cycles for both lines. However, SI decreased in LAS hens, yet
      increased in HAS hens, across cycles (P < 0.001). An interaction between line and
      cycle was observed in WT, SI, ESW, and EST (P < 0.001), but only for WT did the
      interaction cause re-ranking across cycles. Egg quality was, generally, superior
      in HAS compared with LAS hens, suggesting that higher antibody response may
      maintain overall fitness.

PMID- 23155010
TI  - Twenty-five years of selection for improved leg health in purebred broiler lines
      and underlying genetic parameters.
AB  - Leg health is an important component of broiler welfare and the economics of
      broiler production. This study presents the development of leg health in 3
      purebred commercial broiler lines during 25 yr of selection and investigates the
      genetic background of leg health traits in current populations of these lines.
      The leg health traits were deformities of the long bones (LD) and crooked toes
      (CT), recorded since 1985, and tibial dyschondroplasia (TD) and hock burn (HB),
      recorded since 1990. The prevalence of CT and HB decreased mainly in the first
      decade (range among lines -1.2 to -2.3% and -1.3 to -1.5% per year,
      respectively), after which it stabilized at low levels. The prevalence of LD and
      TD decreased by -0.6 to -0.9% and -0.4 to -1.2% per year, respectively. Genetic
      parameters were estimated using data from 4 recent generations. The BW ranged
      from 2.0 to 2.4 kg at 5 wk of age; the prevalences of LD, CT, TD, and HB from 8.6
      to 12.9%, 0.6 to 2.6%, 4.6 to 8.0%, and 4.0 to 12.2%, respectively. Estimates of
      heritability were 0.04 to 0.07 for LD, 0.01 to 0.10 for CT, 0.10 to 0.27 for TD,
      and 0.06 to 0.09 for HB (all SE <=0.01). Estimates of the genetic correlations
      between LD and CT were 0.11 to 0.43 (all SE <=0.09), between these traits and HB
      were negligible, and of TD with LD, CT, and HB were -0.26 to 0.16 (all SE
      <=0.11). Estimates of genetic correlations between the leg health traits and BW
      were lowly to moderately unfavorable, ranging from 0.09 to 0.37 (all SE <=0.06).
      The differences between the lines suggest that strategies for simultaneous
      improvement of all traits tailored for each line individually have been
      effective. This research demonstrates the long-term effectiveness of selection
      for improving leg health in broilers and highlights that, despite somewhat
      unfavorable genetic correlations with BW, these traits can be improved
      simultaneously in a balanced breeding program.

PMID- 23155011
TI  - Breeding for high specific immune reactivity affects sensitivity to the
      environment.
AB  - Lipopolysaccharides (LPS) are present in high levels in the air of chicken houses
      and likely have immune-modulating effects. In this study, layers from the 30th
      generation of a divergent selection experiment for humoral immune reactivity to
      subcutaneously administered sheep red blood cells were concurrently
      intratracheally challenged with human serum albumin (HuSA) and LPS at 7 and 12 wk
      of age following a crossing over design. Chickens selected for high humoral
      immune reactivity (H line) showed higher specific antibody responses to
      intratracheally administered HuSA and a higher level of natural antibody binding
      keyhole limpet hemocyanin compared with chickens genetically selected for low
      humoral immune reactivity (L line), and were also more sensitive to immune
      modulation by LPS at 7 wk of age. Body weight gain was negatively affected by LPS
      at 7 wk of age in the L line, but after 12 wk of age in the H line. Egg
      production was lower and delayed in the H line. We conclude that these chicken
      selection lines differ in sensitivity to the environment (LPS), and consequently
      may therefore also react differently to infection, vaccinations, and other immune
      responses. In addition, selection for immune responsiveness affected growth and
      egg lay.

PMID- 23155012
TI  - Avian infectious bronchitis and deep pectoral myopathy - a case control study.
AB  - Infectious bronchitis is caused by a coronavirus, infectious bronchitis virus
      (IBV). Infectious bronchitis is an acute and highly contagious disease of
      economic importance due to the reduction in weight gain observed with infected
      broilers and the drop in egg quality and production associated with infected
      laying hens. The presence of deep pectoral myopathy has been associated with IBV
      variants. This lesion is detected at slaughterhouses and is characterized by
      paleness and atrophy of the deep pectoral muscle, including necrosis of the
      region, leading to condemnations of the breast muscle, a valuable meat cut in the
      market. This work aimed to study the relationship between deep pectoral myopathy
      and IBV by describing tracheal and muscle lesions and comparing the frequency of
      IBV detection via reverse-transcription (RT) PCR in muscle, tracheal, and cecal
      tonsil samples from broilers with and without myopathy. A case-control study was
      conducted in 40 broiler flocks vaccinated with the Massachusetts strain. The case
      group consisted of 23 flocks that presented myopathic lesions under sanitary
      inspection and a control group of 17 flocks without myopathic lesions. The
      tracheal, cecal tonsil, and supracoracoid muscle (with and without lesions)
      samples from the 40 broiler flocks were screened by RT-PCR to detect IBV.
      Histopathology of muscle and tracheal tissue was carried out. Upon microscopic
      examination, the muscle samples from the case group presented extensive necrosis,
      intense mononuclear inflammatory infiltration, muscle fiber fragmentation, and
      fibrotic tissue, confirming myopathy, whereas muscles from the control group
      showed no alterations. The tracheal samples presented a large number of
      infiltrated mononuclear inflammatory cells that in some areas formed submucosal
      nodules. A total of 25 flocks tested IBV positive by RT-PCR: 14 from the case
      group and 11 from the control group. The IBV was detected by RT-PCR directly in
      muscle samples. Despite that, the relationship between deep pectoral myopathy and
      IBV was not established. The higher positive IBV RT-PCR percentage noted in the
      cecal tonsil samples demonstrates how important the choice of organs is for
      diagnostic purposes.

PMID- 23155013
TI  - Comparison of water-based foam and carbon dioxide gas mass emergency depopulation
      of White Pekin ducks.
AB  - The mass depopulation of production birds remains an effective means of
      controlling fast-moving, highly infectious diseases such as avian influenza and
      virulent Newcastle disease. Two experiments were performed to compare the
      physiological responses of White Pekin commercial ducks during foam depopulation
      and CO(2) gas depopulation. Both experiment 1 (5 to 9 wk of age) and 2 (8 to 14
      wk of age) used electroencephalogram, electrocardiogram, and accelerometer to
      monitor and evaluate the difference in time to unconsciousness, motion cessation,
      brain death, altered terminal cardiac activity, duration of bradycardia, and
      elapsed time from onset of bradycardia to onset of unconsciousness between foam
      and CO(2) gas. Experiment 2 also added a third treatment, foam + atropine
      injection, to evaluate the effect of suppressing bradycardia. Experiment 1
      resulted in significantly shorter times for all 6 physiological points for CO(2)
      gas compared with foam, whereas experiment 2 found that there were no significant
      differences between foam and CO(2) gas for these physiological points except
      brain death, in which CO(2) was significantly faster than foam and duration of
      bradycardia, which was shorter for CO(2). Experiment 2 also determined there was
      a significant positive correlation between duration of bradycardia and time to
      unconsciousness, motion cessation, brain death, and altered terminal cardiac
      activity. The time to unconsciousness, motion cessation, brain death, and altered
      terminal cardiac activity was significantly faster for the treatment foam +
      atropine injection compared with foam. Both experiments showed that bradycardia
      can occur as a result of either submersion in foam or exposure to CO(2) gas. The
      duration of bradycardia has a significant impact on the time it takes White Pekin
      ducks to reach unconsciousness and death during depopulation.

PMID- 23155014
TI  - Reduced lesions in chickens with Clostridium perfringens-induced necrotic
      enteritis by Lactobacillus fermentum 1.20291.
AB  - Previous studies have demonstrated that Lactobacillus has anti-inflammatory
      properties, but the protective functions of Lactobacillus and mechanisms of
      inhibition of necrotic enteritis (NE) in the intestines of chickens have not been
      fully clarified. In the present study, we selected a probiotic strain,
      Lactobacillus fermentum 1.2029, which has good adhesive ability and a high
      survival rate in low pH and bile salts. The objective of this study was to
      examine the anti-inflammatory properties of L. fermentum 1.2029 against NE in
      chickens. Two hundred forty 1-d-old male Arbor Acres broilers were blocked into 3
      experimental groups as follows: (I) nonchallenge control group, (II) Clostridium
      perfringens challenge group, and (III) C. perfringens challenge + L. fermentum
      1.2029 group. Lactobacillus fermentum 1.2029 (1.0 mL/d, 10(8) cfu/mL) was orally
      administered daily to group III during the course of the experiment, and all
      uninfected control chickens were inoculated accordingly with the same volume of
      PBS. Clostridium perfringens (0.5 mL on d 1 and 1.0 mL on d 14 to 21, 10(8)
      cfu/mL) was administered to chickens in group II. At 28 d, scoring of gross NE
      lesions was performed. Ileal segments of approximately 2 cm from 24 chickens in
      each experimental group were collected and fixed in 4% (wt/vol) neutral-buffered
      formalin solution for histological scoring. Ileal mucosa samples were also
      collected for mRNA analysis by real-time PCR. The results showed that L.
      fermentum 1.2029 reduced the severity of NE lesions in chickens. Histological
      scores revealed that L. fermentum 1.2029 also reduced the inflammation damage of
      NE in chickens. Changes in cytokines and Toll-like receptors (TLR) were
      determined, and L. fermentum 1.2029 was found to increase interleukin-10 levels
      and reduce interferon-gamma and TLR2 levels in NE-infected chickens. The results
      showed that L. fermentum 1.2029 was able to regulate the intestinal mucosal
      immune response and ameliorate inflammation by changing expression levels of
      cytokines and TLR.

PMID- 23155015
TI  - Mycoplasma gallisepticum transmission: comparison of commercial F-strain vaccine
      versus layer complex-derived field strains in a tunnel ventilated house.
AB  - Two simultaneous trials were conducted using a commercially available, live, F
      strain Mycoplasma gallisepticum (FMG) vaccine (trial 1) or 2 inocula of layer
      complex-derived MG strains (LCD-MG; trial 2). In each of the 2 trials, 4
      commercial turkeys were housed in each of 2 adjoining pens immediately adjacent
      to air inlets. The turkeys (8/trial) were inoculated in the right eye with either
      a 1* dose of FMG (trial 1) or with 0.02 mL of 1 of 2 actively growing LCD-MG
      inocula (4 turkeys/inoculum; trial 2). In each of the 2 trials, one pen housing 4
      inoculated turkeys was maintained without the addition of other poultry, whereas
      16 MG-free broilers and 4 MG-free layers were added to the other pen of 4
      inoculated turkeys. Within each of the trials and at increasing intervals, either
      4 layers (3 pens) or 4 turkeys (3 pens) were placed down-airstream from the
      inoculated pens. The distance of the first pen from the inoculated turkeys was
      separated by the width of one pen that was empty. Succeeding down-airstream pens
      were situated such that the empty distance (absence of any poultry) between pens
      that contained poultry doubled from one pen to the next such that the final pen
      that contained poultry had 4 empty pens between it and the next up-airstream pen
      that also contained poultry. At 106 d postinoculation, all poultry were bled,
      swabbed for MG from the choanal cleft, and then euthanized and necropsied. No
      commingled poultry in trial 1 (FMG), whether inoculated (turkeys) or commingled
      (layers and broilers), died during the course of the trial, and 5 of the 8 FMG
      vaccinated turkeys exhibited serological but not cultural evidence of
      mycoplasmosis. In trial 2 (LCD-MG), 2 commingled broilers died and no inoculated
      turkeys exhibited either serological or cultural evidence of mycoplasmosis. In
      both trials, no poultry housed down-airstream from the inoculated poultry showed
      evidence of clinical signs of mycocplasmosis and none showed either serological
      or cultural evidence of mycoplasmosis.

PMID- 23155016
TI  - Simultaneous detection of Clostridium perfringens and Clostridium colinum by
      duplex-polymerase chain reaction.
AB  - In this study, we provide a protocol for detection of Clostridium colinum and
      Clostridium perfringens by the single-tube duplex-PCR (dPCR) test for
      simultaneous and specific detection of both bacteria from pure cultures and fecal
      samples spiked with these pathogens. Specific primers for each pathogen were
      selected that amplified products of predicted sizes from bacteria in the dPCR as
      well as in the single-tube PCR (sPCR) assays. The sensitivity and specificity of
      dPCR assay were compared with those of the sPCR. No product amplification was
      obtained with DNA from reference strains belonging to the genus Clostridium
      (except C. colinum and C. perfringens) and isolates belonging to other genera
      using these primer sets. The dPCR assay was as sensitive as the sPCR assay
      because bacterial detection limits were similar in both assays. The detection
      limits of sPCR and dPCR in bacterial suspension were 20 and 25 cfu/mL for C.
      colinum and C. perfringens, respectively. Meanwhile, in the presence of feces the
      sensitivity of both assays decreased to a detection limit of 1.25 * 10(4) and
      1.94 * 10(4) cfu/g of feces for C. colinum and C. perfringens, respectively. In
      summary, dPCR assay holds potential to be an economical and rapid diagnostic
      method for the simultaneous detection of C. colinum and C. perfringens in pure
      cultures and could be used to screen fecal samples for the presence of these
      pathogens.

PMID- 23155017
TI  - Characterization of low-pathogenicity H5 and H7 Korean avian influenza viruses in
      chickens.
AB  - To date, all isolated highly pathogenic avian influenza (HPAI) viruses that cause
      systemic infection with a high mortality rate in poultry species have been known
      to belong to either the H5 or H7 subtypes. The HPAI viruses may originate because
      of the insertion of multiple basic amino acids at the cleavage site of the
      hemagglutinin protein after the low-pathogenic H5 and H7 viruses have been
      introduced into poultry. In the present study, we investigated the phylogenetic
      characteristics of the H5 (n = 4) and H7 (n = 3) low-pathogenic avian influenza
      (LPAI) viruses isolated from wild birds in Korea by using nucleotide sequences of
      all 8 gene segments of the viral genome. Further, we evaluated the infectivity,
      transmissibility, and pathogenic potential of these viruses in chickens.
      Phylogenetic analysis showed that all viruses used in the study clustered in the
      Eurasian lineage and were similar to the viruses isolated in Asian countries that
      share the East Asian-Australasian migratory bird flyway. Our H5N2 isolates could
      not be replicated and transmitted in chickens, but the H7N8 isolates could
      efficiently be replicated and transmitted to contact-exposure chickens. In
      addition, because our H7N8 isolates caused watery diarrhea in chickens, these
      viruses cannot only serve as progenitors of novel HPAI strains but also
      potentially cause clinical disease in poultry. Although there have been no
      reports of LPAI mutation to HPAI in these regions, the wild bird surveillance
      effort should focus on monitoring the introduction and transmission of the HPAI
      H5N1 and LPAI H5 and H7 viruses.

PMID- 23155018
TI  - Immunomodulatory activity accompanying chicken egg yolk immunoglobulin Y.
AB  - Immunity transfer from a mother to the newborn does not depend exclusively on
      immunoglobulins. Peptides, which are characterized by immunoregulatory properties
      that accompany IgG(2), known as proline-rich polypeptide complex (PRP), have been
      discovered for the first time in ovine colostrum. In this report we present new
      data showing that some immunoregulatory peptides associated with the main
      immunoglobulin class, IgY, are also present in the avian immune system. Cytokine
      inducing activity of particular fractions obtained from ovine colostrum, IgG+
      (IgG(2) containing PRP), IgG- (IgG(2) free of PRP), and purified PRP, was
      compared with that of crude egg yolk IgY (IgY+), additionally purified egg yolk
      IgY (IgY-), and polypeptides accompanying IgY named Yolkin (Y), using an ex vivo
      model of whole human blood cells. It was shown that both IgG+ fraction and PRP,
      but not IgG-, stimulated the whole blood cells to release tumor necrosis factor
      alpha and interleukin-1beta cytokines. Similar experiments performed with hen's
      egg IgY preparations showed that IgY+ and Y samples showed higher cytokine
      inducing activity than samples additionally purified with the use of size
      exclusion chromatography (IgY-). The IgY+ at a dose of 100 MUg was even more
      active than the positive lipopolysaccharide control. It was also found that Y is
      able to stimulate macrophage cell line J774.2 to release nitric oxide. The
      results obtained suggest that IgY, the main chicken immunoglobulin fraction, is
      accompanied by additional polypeptides and plays a role of a transporter of
      biologically active substances, which was observed in the case of colostral IgG.

PMID- 23155019
TI  - Effects of feeding regimen, fiber inclusion, and crude protein content of the
      diet on performance and egg quality and hatchability of eggs of broiler breeder
      hens.
AB  - A 12-wk experiment was conducted to study the effects of feeding regimen,
      inclusion of a fiber source, and CP content of the diet on performance of broiler
      breeder hens. In total, 360 hens and 60 males, 43 wk of age, were assigned to 60
      floor pens (6 hens and 1 male each). There were 12 treatments arranged
      factorially with 2 feeding regimens [restricted (R) and liberal feeding (close to
      ad libitum consumption; LIB)], 3 sources of fiber (0, 3% inulin, and 3%
      cellulose), and 2 levels of CP (14.5 and 17.4%). No interactions among main
      effects were observed for any of the traits studied, and therefore, only main
      effects are presented. Body weight, liver weight, and abdominal fat weight were
      higher (P < 0.001) for the LIB than for the R-fed hens. However, egg production
      (P < 0.001), fertility index (P < 0.05), and percentage of hatch (P < 0.01) were
      lower for LIB than for R hens. The weights of ovaries (P < 0.05) and the size of
      the first preovulatory follicle (P < 0.05) were higher for the LIB than for the R
      hens. Also, egg yolk, egg weight, and BW of the hatching chicks were higher (P <
      0.001) for the LIB hens. The inclusion of a fiber source in the diet decreased (P
      < 0.05) feed intake, BW gain, absolute liver and abdominal fat weight, and egg
      yolk weight, with effects being more pronounced (P < 0.05) with cellulose than
      with inulin. Hens fed additional fiber produced more (P < 0.05) eggs that were
      more fertile (P < 0.05) than control hens. Crude protein content of the diet did
      not affect hen performance but reduced (P < 0.01) the relative weight of the
      liver, ovary, and abdominal fat. It is concluded that the inclusion of inulin or
      cellulose in the diet improved hen performance and that an increase in dietary CP
      reduced obesity in broiler breeder hens.

PMID- 23155020
TI  - Dietary fibers and crude protein content alleviate hepatic fat deposition and
      obesity in broiler breeder hens.
AB  - The effects of inclusion of cellulose or inulin as a source of dietary fiber and
      CP content of the diet on hepatic fat deposition were investigated in hens fed
      restricted or close to ad libitum consumption. There were 12 dietary treatments
      forming a 2 * 3 * 2 factorial with 2 feeding regimens [restricted and liberal
      (close to ad libitum consumption; LIB)], 3 fiber sources (control, 3% inulin, and
      3% cellulose), and 2 levels of CP (14.5 and 17.4%). Hens were assigned in groups
      of 6 to 60 floor pens. From 43 to 55 wk of age, hens fed LIB showed increased
      activity of the hepatic malic enzyme (MalE; P < 0.01), which led to an increase
      (P < 0.001) in liver weight and hepatic lipid deposition and was associated with
      enhancements (P < 0.05) in plasma levels of glucose, triglyceride, total
      cholesterol, and low-density lipoprotein cholesterol. Abdominal fat deposition
      and BW of the hens increased (P < 0.001) with liberal feeding. Inclusion of
      inulin in the diet reduced (P < 0.05) liver and abdominal fat weight, whereas
      cellulose inclusion decreased (P < 0.05) feed intake, abdominal fat, and BW. An
      increase in CP content of the diet from 14.5 to 17.4% reduced MalE activity (P <
      0.001), liver weight (P < 0.001), and the accumulation of lipids and cholesterol
      in the liver, as well as plasma triglyceride concentration and abdominal fat pad
      weight (P < 0.05). It is concluded that fiber inclusion reduced abdominal fat and
      liver weight, with effects being more pronounced with cellulose than with inulin.
      An increase in dietary CP reduced MalE activity and alleviated hepatic and plasma
      lipid concentration; therefore, it might be a practical approach to reduce the
      incidence of obesity-linked problems in broiler breeder hens. The combination of
      high-CP diets and the inclusion of a fiber source did not suppress liver lipid
      content over that observed with the high-CP diet, exclusively.

PMID- 23155021
TI  - Bioavailability of organic and inorganic zinc sources in male broilers.
AB  - The objective of the current study was to determine the bioavailability of an
      organic zinc source (Availa-Zn) compared with zinc sulfate in a European-type
      broiler diet. A total of 480 one-day-old male Ross 308 broilers were housed in 48
      digestibility cages (10 birds per cage), being randomly divided over 9
      treatments. At d 3, the number of birds was standardized to 8. Birds were fed a
      basal wheat-maize-soya diet (containing 33.5 mg of Zn/kg) with different
      supplementation levels of zinc (reference zinc source: inorganic zinc sulfate: 0,
      5, 10, 15, 20, and 40 mg of Zn/kg of feed; test zinc source: Availa-Zn: 0, 5, 10,
      15 mg of Zn/kg of feed). Production performance and tibia zinc content were
      measured. There were no differences in production performance between the
      different zinc sources when fed to broilers until 21 d of age. Tibia zinc content
      was increased linearly with the dietary zinc content up to 20 mg/kg zinc sulfate.
      The relative biological value of organic zinc was 1.64 compared with zinc sulfate
      as a reference zinc source (1.00), as indicated by the slope ratio of the linear
      response curves for both zinc sources, using tibia zinc content as a response
      parameter. In a practical European broiler diet, the organic Availa-Zn had a
      higher bioavailability than inorganic zinc sulfate.

PMID- 23155022
TI  - Evaluation of probiotic strains for development of fermented Alisma canaliculatum
      and their effects on broiler chickens.
AB  - The present study was conducted to select appropriate microbial strains for the
      development of fermented Alisma canaliculatum A. Br. et Bouche (FAC) feed
      additive and to examine their effects on broilers. In experiment 1, 16 strains of
      Lactobacillus acidophilus, Lactobacillus plantarum, Enterococcus faecium,
      Bacillus subtilis, Bacillus coagulans, and Saccharomyces cerevisiae from the
      Korean Collection for Type Cultures (KCTC) were evaluated. The strains were
      tested for their acid, bile, and heat tolerance levels. Among them, L.
      acidophilus KCTC 3111, E. faecium KCTC 2022, B. subtilis KCTC 3239, and S.
      cerevisiae KCTC 7928 were selected to produce FAC. For experiment 2, 140 Ross
      broiler chicks were allocated to four 5-wk-long dietary groups: NC (basal diet),
      PC (basal diet with 0.005% oxytetracycline), AC (basal diet with 0.5% A.
      canaliculatum rhizome powder), and FAC (basal diet with 0.5% FAC). Final BW and
      total BW gain were increased (P < 0.05) upon the addition of FAC, whereas feed
      conversion ratio improved (P < 0.05) in the supplemented groups compared with the
      NC group. Crude protein content increased and crude fat decreased (P < 0.05) in
      the breast meat of the FAC group compared with the AC and PC groups,
      respectively. Proventriculus and kidney relative weights of the FAC group
      differed (P < 0.05) from the AC group but not from the PC group. Lower (P < 0.05)
      thiobarbituric acid reactive substances value of thigh meat was observed in the
      FAC group compared with the other groups. The FAC diet increased (P < 0.05) alpha
      linolenic acid and linoleic acid in meat. Alteration of these fatty acids led to
      increased levels of polyunsaturated fatty acid, polyunsaturated fatty acid
      /saturated fatty acid, n-3 and n-6 fatty acids, and decreased n-6/n-3 ratio in
      breast or thigh meat (P < 0.05). It is concluded that FAC confers high tolerance
      to acid, bile and heat; and beneficially affects growth, meat composition,
      oxidative stability, and fatty acid composition. The FAC may be a functional feed
      additive in broilers.

PMID- 23155023
TI  - Effects of oligosaccharides in a soybean meal-based diet on fermentative and
      immune responses in broiler chicks challenged with Eimeria acervulina.
AB  - Fermentable oligosaccharides, particularly those found in soybean meal (SBM), may
      modulate fermentation in the ceca, thus affecting intestinal immune responses to
      intestinal pathogens. We hypothesized that fermentable oligosaccharides found in
      SBM would positively affect cecal fermentation and intestinal immune status in
      chicks challenged with an acute coccidiosis (Eimeria acervulina) infection and
      fed either a SBM-based diet or a semi-purified soy protein isolate- (SPI) based
      diet. Using a completely randomized design, 1-d-old broiler chicks (n = 200; 5
      replications/treatment; 5 chicks/replication) were assigned to 1 of 4 SBM- or SPI
      based diets containing either dietary cellulose (4%) or a fermentable
      carbohydrate, galactoglucomannan oligosaccharide-arabinoxylan (GGMO-AX) complex
      (4%). On d 9 posthatch, an equal number of chicks on each diet were inoculated
      with either distilled water (sham control) or E. acervulina (1 * 10(6) oocysts)
      and then euthanized on d 7 postinoculation. Overall, body weight gain and feed
      intake were greater (P < 0.01) for SBM-fed chicks, regardless of infection
      status. Gain:feed ratio was greater (P <= 0.05) for SPI-fed chicks except during
      d 3-7 postinoculation. Infection status, but not fiber source, affected
      propionate, isobutyrate, isovalerate, and total branched-chain fatty acid
      concentrations (P <= 0.02). Soybean meal-based diets resulted in greater (P <=
      0.04) short-chain fatty acid and branched-chain fatty acid concentrations than
      SPI-based diets. Messenger RNA fold changes relative to uninfected SBM-cellulose
      fed chicks of all duodenal cytokines were greater (P <= 0.01) for infected
      chicks, and SBM-fed chicks had greater (P < 0.01) interferon-gamma and
      interleukin-12beta expression compared with SPI-fed chicks. Cecal tonsil cytokine
      expression was also affected (P <= 0.02) by infection; however, protein source
      only affected (P < 0.01) interleukin-1beta expression in this tissue. Overall, a
      SBM-based diet, compared with a semi-purified SPI-based diet with a different
      ingredient composition, resulted in greater weight gain, feed intake, and short
      chain fatty acid production regardless of infection status, and also greater
      duodenal cytokine expression in E. acervulina- infected chicks, which is
      hypothesized to be related to the nutrients and oligosaccharides found in SBM.

PMID- 23155024
TI  - Comparison of amino acid digestibility coefficients for corn, corn gluten meal,
      and corn distillers dried grains with solubles among 3 different bioassays.
AB  - The objective of this study was to determine standardized AA digestibility of
      corn, corn gluten meal, and 3 distillers dried grains with solubles (DDGS) using
      the precision-fed cecectomized rooster assay (PFR), the standardized ileal AA
      broiler chicken assay (SIAAD), and a newly developed precision-fed ileal broiler
      chicken assay (PFC). For the PFR, cecectomized roosters were precision-fed
      approximately 30 g of feed sample, and excreta were collected 48 h postfeeding.
      For the SIAAD, 16-d-old broilers were ad libitum fed a semi-purified diet
      containing the feed samples as the sole source of protein from 17 to 21 d, with
      ileal digesta collected at 21 d. For the PFC, 22-d-old broiler chickens were
      precision-fed 10 g of feed and ileal digesta were collected at 4 h postfeeding.
      For corn, the PFC yielded significantly higher digestibilities than the SIAAD and
      PFR for several AA. For corn gluten meal, the PFR yielded significantly higher
      values than the PFC for the majority of the AA, with the SIAAD yielding
      intermediate values. When 3 DDGS samples were evaluated, the PFR produced higher
      digestibilities than the PFC for all 3 DDGS samples for most of the AA. When
      comparing the PFR and the SIAAD, the PFR yielded higher values than the SIAAD for
      one DDGS, whereas there was generally no significant difference between these 2
      methods for the other 2 DDGS samples. The results of this study indicate there
      were differences among standardized AA digestibility values for the PFR, SIAAD,
      and PFC in some instances. The differences among methods were not consistent;
      however, the PFR yielded higher digestibility values than the PFC for 4 of the 5
      ingredient samples.

PMID- 23155025
TI  - Commercially available amino acid supplementation of low-protein diets for
      broiler chickens with different ratios of digestible glycine+serine:lysine.
AB  - This work studied the effect of supplementing commercially available amino acids
      in low-protein diets using different ratios of digestible (dig)
      glycine+serine:lysine (Gly+Ser:Lys) on performance, serum parameters, feathering,
      and litter characteristics of broiler chickens during the starter period. A total
      of one thousand fifty 1-d-old Cobb-Vantress male chicks were distributed in a
      completely randomized experimental design into 6 treatments with 5 replicates of
      35 birds each. The treatments were as follows: T1, control diet based on corn and
      soybean meal formulated with 22% CP (dig Gly+Ser:Lys ratio of 147); T2, diet with
      a 2% CP reduction, supplemented with Val (dig Gly+Ser:Lys ratio of 137); T3,
      similar to T2 with the addition of Gly (dig Gly+Ser:Lys ratio of 147); T4, diet
      with a 3% CP reduction, supplemented with Val, Ile, and Arg (dig Gly+Ser:Lys
      ratio of 127); and T5 and T6, similar to T4 with the addition of Gly (dig
      Gly+Ser:Lys ratios of 137 and 147, respectively). At 7 and 21 d, broilers that
      had received diets with a 3% CP reduction (19% CP) and a Gly+Ser:Lys ratio that
      was equivalent to 127 had lower G:F (P < 0.05) and lower total protein and
      albumin serum concentrations (P < 0.05) than those broilers that received the
      control feed. However, these parameters were restored to the same level as the
      control diet with an increase in the dig Gly+Ser:Lys ratio from 127 to 137 and
      147. Diets with a 3% CP reduction (19% CP) resulted in litter with reduced (P <
      0.05) nitrogen content and lower ammonia emission than the litter of broilers
      receiving the control diet. The treatments did not influence (P > 0.05) the
      feather length or feathering scores at 21 or 28 d of age. The supplementation of
      essential amino acids while maintaining dig Gly+Ser:Lys ratios at and above 137
      allowed for a reduction in the dietary CP of 3% without undermining the
      performance, feathering or serum parameters of early stage broilers.

PMID- 23155026
TI  - Effects of energy concentration of the diet on productive performance and egg
      quality of brown egg-laying hens differing in initial body weight.
AB  - The influence of AME(n) concentration of the diet on productive performance and
      egg quality traits was studied in Hy-Line brown egg-laying hens differing in
      initial BW from 24 to 59 wk of age. Eight treatments were arranged factorially
      with 4 diets varying in energy content (2,650, 2,750, 2,850, and 2,950 kcal of
      AME(n)/kg) and 2 initial BW of the hens (1,733 vs. 1,606 g). Each treatment was
      replicated 5 times (13 hens per replicate), and all diets had similar nutrient
      content per unit of energy. No interactions between energy content of the diet
      and initial BW of the hens were detected for any trait. An increase in energy
      concentration of the diet increased (linear, P < 0.05; quadratic P < 0.05) egg
      production, egg mass, energy efficiency (kcal of AME(n)/g of egg), and BW gain (P
      < 0.05) but decreased ADFI (linear, P < 0.001) and feed conversion ratio per
      kilogram of eggs (linear, P < 0.01; quadratic P < 0.01). An increase in energy
      content of the diet reduced Haugh units and the proportion of shell in the egg (P
      < 0.01). Feed intake (114.6 vs. 111.1 g/hen per day), AME(n) intake (321 vs. 311
      kcal/hen per day), egg weight (64.2 vs. 63.0 g), and egg mass (58.5 vs. 57.0 g)
      were higher for the heavier than for the lighter hens (P < 0.01), but feed
      conversion ratio per kilogram of eggs and energy efficiency were not affected.
      Eggs from the heavier hens had a higher proportion of yolk and lower proportion
      of albumen (P < 0.01) and shell (P < 0.05) than eggs from the lighter hens.
      Consequently, the yolk-to-albumen ratio was higher (P < 0.001) for the heavier
      hens. It is concluded that brown egg-laying hens respond with increases in egg
      production and egg mass to increases in AME(n) concentration of the diet up to
      2,850 kcal/kg. Heavy hens had higher feed intake and produced heavier eggs and
      more egg mass than light hens. However, feed and energy efficiency were better
      for the lighter hens.

PMID- 23155027
TI  - Gene pathways and cell cycle-related genes in cultured avian primordial germ
      cells.
AB  - Primordial germ cells (PGC) from early embryos are applicable to various kinds of
      research, including the production of transgenic animals. Primordial germ cells
      eventually migrate and differentiate into germ cells in the gonads, where they
      settle and rapidly proliferate. However, the proliferation rate of PGC is low in
      early embryos, and there are many significant pathways that mediate PGC activity.
      Therefore, in vitro culture of PGC from early embryos with efficient growth
      factors has been necessary. Recently, we cultured chicken PGC from embryonic d
      2.5 with basic fibroblast growth factor and characterized the PGC through
      analysis of cell morphology, survival, proliferation, and apoptosis. However,
      large-scale analyses of genes expressed in cultured PGC and the genes involved in
      associated pathways are limited. The objective of the present investigation was
      to identify the signaling and metabolic pathways of expressed genes by microarray
      comparison between PGC and their somatic counterpart, chicken embryonic
      fibroblasts (CEF). We identified 795 genes that were expressed more predominantly
      in PGC and 824 genes that were expressed more predominantly in CEF. Among the
      predominant genes in PGC, 201 were differentially identified in 106 pathways.
      Among the predominant genes in CEF, 242 were differentially identified in 99
      pathways. To further validate the genes involved in at least one candidate
      pathway, those involved in the cell cycle (12 predominant genes in PGC and 8
      predominant genes in CEF) were examined by real-time PCR. To the best of our
      knowledge, this study is the first to investigate signaling and metabolic
      pathways in cultured PGC.

PMID- 23155028
TI  - Feed restriction delays developmental fast skeletal muscle myosin heavy chain
      isoforms in turkey poults selected for differential growth.
AB  - Genetic selection has been very successful at significantly increasing BW and
      breast muscle proportion in commercial broiler and turkey strains. The mechanisms
      of breast muscle growth in poultry and the interactive effects of nutritional
      status and selection are not fully understood. The hypothesis underlying the
      current study is that feed restriction, simply as a vehicle for controlling early
      growth, would delay the temporal expression pattern of neonatal (nMyHC) and adult
      (aMyHC) fast skeletal muscle myosin heavy chain (MyHC) isoforms in the pectoralis
      major muscle of turkey poults. The poultry growth model used to evaluate this
      hypothesis consisted of a randombred control turkey line (RBC2) that represents
      commercial turkeys of the 1960s and a line developed from the RBC2 by selection
      for BW at 16 wk of age (F line). The F line has significantly heavier breast
      muscles than the RBC2 concomitant with increased BW, but the proportion of breast
      muscle relative to BW is similar. A quantitative indirect ELISA using fast
      skeletal MyHC isoform specific monoclonal antibodies revealed no significant line
      differences in the temporal expression of posthatch fast skeletal muscle MyHC in
      ad libitum fed poults. Feed restriction, however, altered the temporal expression
      patterns of nMyHC and aMyHC in both F line and RBC2 poults compared with the
      poults fed ad libitum.

PMID- 23155029
TI  - Microarray analysis revealed that immunity-associated genes are primarily
      regulated by roxarsone in promoting broiler chicken (Gallus gallus domesticus)
      growth.
AB  - Addition of roxarsone can significantly improve the growth of broiler chickens
      (Gallus gallus domesticus). Nevertheless, this application will lead to the
      contamination of the environment as well as animal products. Understanding the
      response of genes to roxarsone may bring about the discovery of new, safer
      substitutes. In this study, we monitored the expression of 8,935 genes in chicken
      breast muscle using microarrays. Analysis showed that 30 genes, such as the
      interleukin 3 regulated nuclear factor (NFIL3), the regulatory factor X
      associated ankyrin-containing protein (RFXANK), the cleavage and polyadenylation
      specific factor 3 (CPSF3), and the FK506 binding protein 9 (FKBP9), have
      consistently up or downregulated (fold change >=1.5 or <=0.6, P < 0.05, false
      discovery rate <=0.05) throughout the medication periods. The results from
      microarray analysis were validated by real-time quantitative PCR. Further
      functional investigation showed that 13 of the identified genes are well
      documented, and surprisingly, 11 (85%) of these are related to immunity (5 are
      immunity and defense related, 4 are immunodeficiency disease related, 2 are
      immunosuppressive drug related), and the remaining 2 are energy metabolism
      related. These findings may suggest that supplement of roxarsone can improve the
      immunity of chickens through regulating the expression of associated genes, and
      as a result contribute to the growth promotion. Further research on the encoded
      proteins of the differentially expressed genes should provide more evidence for
      the potential mechanism.

PMID- 23155030
TI  - Hypoxic level and duration differentially affect embryonic organ system
      development of the chicken (Gallus gallus).
AB  - Hypoxia inhibits avian embryonic development, as well as increases embryonic
      mortality. However, the key organ systems affected by hypoxia, and their critical
      windows for development, are poorly understood. Consequently, chicken embryos
      were continuously exposed to 3 levels of oxygen (21, 15, or 13% O(2)) throughout
      d 0 to 10, d 11 to 18, or d 0 to 18 of incubation, followed by morphometric and
      blood physiological measurements. Hypoxia occurring early during incubation (d 0
      to 10) had larger effects on embryonic mortality and organ growth than hypoxia
      occurring at later stages (d 10 to 18). Growth of the heart and chorioallantoic
      membrane was stimulated by chronic hypoxia, whereas the lung, brain, eye, liver,
      stomach, beak, and toes showed no disruption. Sustained hypoxia from the
      beginning of incubation decreased blood hemoglobin, hematocrit, and red blood
      cell concentration of embryos at d 10, but the values among hypoxic and normoxic
      groups were not significantly different at d 18. Blood partial pressure of O(2)
      and partial pressure of CO(2) were dependent upon incubation O(2) level at a
      given day of development. These results indicated that either modest hypoxia (15%
      O(2)) throughout development, or hypoxia at any level during the late stages (d
      11 to 18), increased the heart and chorioallantoic membrane weight, which partly
      compensated for the detrimental effects of hypoxia on embryonic development. We
      conclude that the first half of embryonic development contained the critical
      windows for the detrimental effects of hypoxia, and the second half contained the
      critical windows for the compensatory response of hypoxia in key organs.

PMID- 23155031
TI  - Adhesion and invasion to duck embryo fibroblast cells by Riemerella
      anatipestifer.
AB  - Here, we investigated adhesion and invasion of Riemerella anatipestifer (RA) to
      primary duck embryo fibroblast (DEF) cells. The ability of RA to adhere to, and
      more importantly, to invade DEF cells was demonstrated by using a gentamicin
      invasion assay and was confirmed by transmission electron microscopy (TEM).
      Adhesion of RA could be found by TEM after 1 h of inoculation. Both apoptosis and
      necrocytosis of DEF were indicated by TEM after 10 h of incubation, which
      suggested a complex mechanism of DEF cell death induced by RA. Our results showed
      that internalized RA had the ability to leave the DEF cells. Inhibition studies
      indicated that RA proteins play a role in adhesion. Moreover, invasion of RA to
      DEF cells was shown to require rearrangement of actin microfilaments and
      microtubular cytoskeletal elements. Because the adhesion and invasion ability of
      RA to DEF cells could be demonstrated in vitro, similar processes might occur in
      vivo, where DEF cells play a crucial role in the diffusion of RA in ducks.

PMID- 23155032
TI  - A simple vitrification method for cryobanking avian testicular tissue.
AB  - Cryopreservation of testicular tissue is a promising method of preserving male
      reproductive potential for avian species. This study was conducted to assess
      whether a vitrification method can be used to preserve avian testicular tissue,
      using the Japanese quail (Coturnix japonica) as a model. A simple vitrification
      method that included dimethyl sulphoxide, ethylene glycol, and sucrose as
      cryoprotective agents, and allowed the storage of tissue in a sealed macrotube
      was applied to the testicular tissue from 1-wk-old Japanese quail. The vitrified
      tissue was warmed at room temperature or at 40 degrees C. After warming, tissue
      was implanted onto the chorioallantoic membrane of 8- to 9-d-old chicken embryos
      and the vascularization of the grafts was evaluated. When compared with fresh
      tissue, the tissue that had been warmed at 40 degrees C showed no difference in
      vascularization. The tissue that had been warmed at room temperature was
      significantly less vascularized than the fresh tissue. Vitrification of
      testicular tissue and storage in macrotubes provide a promising model for
      preservation and recovery of male germplasm of avian species.

PMID- 23155033
TI  - The effects of low atmosphere stunning and deboning time on broiler breast meat
      quality.
AB  - Research was conducted to determine the effect of stunning method (low atmosphere
      pressure, LAPS, and electrical stunning, ES) and deboning time (0.75 and 4 h) on
      breast meat quality (n = 576, 144 birds per treatment) in a commercial processing
      plant. Breast meat quality was evaluated through determining pH, Commission
      Internationale d'Eclairage L*a*b*, cooking yield, shear force, and consumer
      acceptability. The onset of rigor mortis was more rapid (P < 0.05) in breast meat
      from LAPS-stunned birds compared with ES-stunned birds, but no differences
      existed (P > 0.05) among stunning methods with respect to final pH at 24 h. As
      expected, breast meat that was deboned at 4 h required less shear force (P <
      0.05) to cut through the breast than samples that were deboned at 0.75 h
      postmortem, but no differences existed between breast meat from LAPS or ES
      broilers that were deboned at the same time postmortem. However, when samples
      were marinated with 2% NaCl and 0.5% phosphate, there was no difference in Allo
      Kramer shear force between ES 4 h and LAPS 4-h samples, but the ES 0.75-h samples
      had lower shear force values (P < 0.05) than the LAPS 0.75-h samples. On average,
      the LAPS 4-h treatment had greater overall acceptability ratings (P < 0.05) than
      other treatments, and the ES and LAPS 4-h treatments had more acceptable (P <
      0.05) texture than the ES and LAPS 0.75-h treatments. Cluster analysis revealed
      that the 2 largest consumer groups liked all chicken breast fillet treatments,
      but a larger proportion of consumers liked the 4-h LAPS and ES treatments
      compared with the 0.75-h LAPS and ES treatments. In addition, consumers who rated
      baked chicken breast as at least moderately acceptable preferred (P < 0.05) the 4
      h LAPS samples over the 4-h ES samples. The present study revealed that both the
      LAPS and ES systems can be successfully used in commercial poultry plants without
      detrimental breast fillet quality problems with respect to color, texture, and
      consumer acceptance.

PMID- 23155034
TI  - Evaluation of poultry protein isolate as a food ingredient: physicochemical
      characteristics of low-fat turkey bologna.
AB  - Evaluation of poultry protein isolate (PPI) as a food ingredient was carried out
      by substituting nonmeat ingredients such as soy protein isolate (SPI) or meat
      protein in turkey bologna. Two concentrations (1.5 and 2% dry weight basis) of
      PPI prepared from mechanically separated turkey meat were used in this study. Two
      control samples were prepared with 11 and 13% meat protein, respectively.
      Physicochemical characteristics of turkey bologna containing PPI were compared
      with those of control and SPI-containing samples. Batter strength was higher for
      2% PPI and 13% meat protein control samples (control-2) compared with all other
      treatments. Cooking yield of the 11% meat protein control was significantly (P <
      0.05) less compared with other treatments. However, there was no significant
      difference in the expressible moisture or purge loss among all the treatments.
      Control-2 showed lower L* values and was more reddish during refrigerated
      storage. Addition of protein isolates caused a significant increase (b* value
      varied between 11.48 and 12.52) in yellowness of products. Turkey bologna with
      added protein isolates showed significantly lower lipid oxidation as indicated by
      induced TBA reactive substance analysis. Results from this study suggest that SPI
      or meat protein could be replaced by PPI without negatively affecting product
      characteristics as evident from cooking yield and purge loss values.

PMID- 23155035
TI  - Effect of different levels of dietary vitamin E (DL-alpha-tocopherol acetate) on
      the occurrence of various degrees of white striping on broiler breast fillets.
AB  - White striping could be a potential reason for the rejection of raw breast
      fillets in the market. The condition is characterized grossly by the white
      striations occurring on the fillets showing myopathic changes on microscopic
      examination. Early research has shown similar lesions in the case of nutritional
      muscular dystrophy, which is a condition caused mainly by the deficiency of
      vitamin E in the diet. The present study was intended to evaluate the effect of
      different levels of dietary vitamin E (dl-alpha-tocopherol acetate) on the
      incidence of normal, moderate, and severe degrees of white striping, by modern
      description, on broiler breast fillets. Basal diets adequate for starter (0 to 18
      d), grower (19 to 32 d), and finisher (33 to 49 d) age periods supplemented with
      15, 50, 100, 200, and 400 IU of vitamin E/kg of feed were used in the study. Each
      of the 5 diet treatments were fed to 8 pens (53 birds each) of male broilers from
      a commercial strain. At 49 d, 5 birds were randomly selected from each pen (n =
      40 birds/diet treatment) and were processed. Live weight, ready-to-cook weight,
      weight of the fillets, wings, tenders, legs, and the racks were obtained. The
      fillets were scored for the 3 degrees of white striping. There were no
      significant differences among the diet treatments with respect to the weight and
      carcass yield parameters. Furthermore, the diet treatments did not show any
      significant effect on the occurrence of normal, moderate, and severe degrees of
      white striping. However, fillet weight was the only parameter that had a
      significant effect on the occurrence of white striping. Higher degrees of white
      striping were seen associated with heavier fillets, which is in accordance with
      previous studies. Different levels of vitamin E levels used in the present study
      did not show any significant effect on the occurrence of 3 degrees of white
      striping. These results suggest that dietary vitamin E level is not associated
      with the modern condition of white striping in broiler breast meat.

PMID- 23155036
TI  - Effects of increasing concentrations of corn distillers dried grains with
      solubles on the egg production and internal quality of eggs.
AB  - A study was conducted to determine the effect of feeding high concentrations of
      corn distillers dried grains with solubles (DDGS) on egg production and the
      internal quality of eggs from laying hens. Four diets were formulated to contain
      0, 17, 35, or 50% corn DDGS. A total of two hundred forty 54-wk-old Single-Comb
      White Leghorn laying hens were randomly allotted to 2 birds per cage with 3
      consecutive cages representing an experimental unit (EU). Each EU was assigned to
      1 of 4 dietary treatments according to a completely randomized design. Hens were
      fed for a 24-wk experimental period after transition feeding to gradually
      increase corn DDGS inclusion over a 4-wk period. Two sets of experimental diets
      were formulated, and each diet was fed for 12 wk. Egg production, feed
      consumption, egg component, yolk color, Haugh unit during storage times, and
      shell breaking strength were measured. Egg production, egg weight, egg mass, feed
      intake, and feed efficiency were adversely affected by the highest level of DDGS
      in the diet (50%) during the first 12-wk period. Once diets were reformulated to
      include an increased concentration of both lysine and methionine, differences
      among the dietary treatments were reduced, as the performance of the 50% DDGS
      diets was greatly improved. Over the last 6 wk of study, no differences in egg
      production, egg weight, and feed intake among DDGS treatments were found. The
      DDGS diets positively affected the internal quality of eggs during storage.
      Improved yolk color and Haugh unit were observed as the dietary DDGS levels
      increased, but the increase for Haugh unit was significant only when the DDGS
      level was 50%. Shell weight percentage was increased in the 50% DDGS diet, but no
      differences in yolk and albumen percentage were observed. It was concluded that
      up to 50% of DDGS could be included in the layer's diet without affecting egg
      weight, feed intake, egg mass, feed efficiency, and egg production as long as
      digestible amino acids were sufficient in DDGS-added diets.

PMID- 23155037
TI  - Effect of kosher salt application on microbial profiles of poultry carcasses.
AB  - The effect of conventionally applied kosher salt on the microbiological profile
      of posteviscerated chicken carcasses obtained from a local commercial processing
      facility was evaluated. The broiler carcasses were divided into treatments 1
      through 8. Standard sampling methods were used to evaluate Salmonella prevalence,
      aerobic plate counts, coliforms, generic Escherichia coli, and psychrotroph
      counts. Results indicate significant reductions in microbial populations in all
      the salted groups compared with controls. Significant reductions (1.45, 2.31,
      2.81, and 1.48 log cfu/mL of rinse) were obtained for aerobic plate count (APC),
      coliforms, generic E. coli, and psychrotroph counts, respectively, on prechill
      salt-treated carcasses compared with controls. Salt-treated carcasses sampled
      after chilling had lower microbial populations compared with control chilled
      samples with significant reductions in coliforms and generic E. coli (1.25 and
      1.77 log, respectively). Salt-treated samples had lower counts on APC and
      psychrotrophs after 10 d of refrigerated storage compared with controls. Finally,
      drip loss of salt-treated carcasses was lower after 24 h compared with nontreated
      controls. Based on the results, it can be concluded that salting process is an
      effective contributor to microbial reductions during processing that needs
      further investigation as a possible intervention in commercial poultry processing
      settings.

PMID- 23155038
TI  - Modified-atmosphere packaging of hen table eggs: effects on pathogen and spoilage
      bacteria.
AB  - As part of a more comprehensive research activity on the use of modified
      atmosphere packaging for the improvement of quality and functional properties of
      table eggs, the effects of air, 100% CO(2), and 100% O(2) packaging were also
      evaluated on the survival of experimentally inoculated pathogen bacteria
      (Salmonella Enteritidis, Escherichia coli, and Listeria monocytogenes) as well as
      on spoilage bacteria (total aerobic mesophilic bacteria) on table eggs during 30
      d of storage at 4, 25, and 37 degrees C by colony count method. In general,
      temperatures played a major role, rather than gasses, in influencing the
      bacterial survival. In particular, the lowest microbial loads were registered at
      4 degrees C on E. coli and spoilage bacteria, whereas 37 degrees C was the best
      storage temperature to avoid the psychrotropic microorganism L. monocytogenes
      development regardless of the gas used. One hundred percent CO(2) packaging, in
      association with a low storage temperature (4 degrees C), had a significant
      positive effect in reducing Salmonella loads. On eggs inoculated with L.
      monocytogenes and stored at 4 degrees C as well as on eggs containing only
      spoilage bacteria and stored at 25 degrees C, 100% CO(2) resulted the best gas in
      comparison with air and O(2). One hundred percent CO(2) packaging showed no
      negative effect on pathogen survival compared with air. Although further
      improvements are required to control RH within packaging to limit bacteria
      growth/survival, in view of the positive effects of CO(2) packaging on quality
      traits of table eggs, 100% CO(2) packaging might represent a promising innovative
      technique for the maintenance of egg characteristics during transport, retail,
      and domestic storage.

PMID- 23155039
TI  - Effect of manipulation of incubation temperature on fatty acid profiles and
      antioxidant enzyme activities in meat-type chicken embryos.
AB  - Eggs (n = 1,800) obtained from Ross broiler breeders at 32 and 48 wk of age were
      incubated at either a constant temperature of 37.6 degrees C throughout (T1), or
      the temperature was reduced for 6 h to 36.6 degrees C each day during embryonic
      age (EA) 10 to 18 (T2). Yolk sac, liver, and brain fatty acid profiles and
      oxidant and antioxidant status of liver and brain were measured at EA 14, 19, and
      day of hatch (DOH). Fatty acid profiles of yolk sac, liver, and brain were
      influenced by age of breeder with significant breeder hen age * incubation
      temperature interactions. At EA 14, higher levels of 20:4n-6 and 22:6n-3 had been
      transferred from the yolk sac to T2 embryos from younger than older breeders,
      whereas for T1 and T2 embryos, yolk sac 20:4n-6 and 22.6n-3 values were similar
      for older breeders. Accumulation of 20:4n-6 and 22:6n-3 fatty acids in the liver
      of T1 and T2 embryos from younger breeders was similar; however, T2 embryos from
      older breeders had higher liver levels of 20:4n-6 and 22:6n-3 than T1 embryos. At
      EA 19, liver nitric oxide levels were higher for T2 embryos from younger breeders
      than those from breeders incubated at T1. Brain catalase levels of T2 embryos
      from younger breeders were higher than those from older breeders at DOH. Thus,
      changes in fatty acid profiles and catalase and nitric oxide production of brain
      and liver tissues resulting from 1 degrees C lower incubation temperature from EA
      10 to 18 reflect adaptive changes.

PMID- 23155040
TI  - A model for an economically optimal replacement of a breeder flock.
AB  - A deterministic model is developed to support the tactical and operational
      replacement decisions at broiler breeder farms. The marginal net revenue approach
      is applied to determine the optimal replacement age of a flock. The objective
      function of the model maximizes the annual gross margin over the flock's
      production cycle. To calculate the gross margin, future egg production,
      fertility, or hatchability of the eggs, revenues and variable costs of a flock
      were estimated. For tactical decisions, the optimal laying length is the age at
      which the average gross margin of an average flock is maximal. For operational
      decisions, a flock should be replaced when the marginal gross margin of a
      replaceable flock is less than the average gross margin of an average flock. To
      demonstrate the model, a broiler breeder flock from a Dutch breeder farm was
      used. A sensitivity analysis showed that the optimal replacement decision, for
      both tactical and operational management, is sensitive to the decrease in the
      weekly egg production after the peak and the prices of feed and hatching eggs.
      The effect of the decrease in weekly fertility after the peak on the replacement
      decision is related to the payment system for hatching eggs.

PMID- 23155041
TI  - Development of artificial neural network models based on experimental data of
      response surface methodology to establish the nutritional requirements of
      digestible lysine, methionine, and threonine in broiler chicks.
AB  - An artificial neural network (ANN) approach was used to develop feed-forward
      multilayer perceptron models to estimate the nutritional requirements of
      digestible lysine (dLys), methionine (dMet), and threonine (dThr) in broiler
      chicks. Sixty data lines representing response of the broiler chicks during 3 to
      16 d of age to dietary levels of dLys (0.88-1.32%), dMet (0.42-0.58%), and dThr
      (0.53-0.87%) were obtained from literature and used to train the networks. The
      prediction values of ANN were compared with those of response surface methodology
      to evaluate the fitness of these 2 methods. The models were tested using R(2),
      mean absolute deviation, mean absolute percentage error, and absolute average
      deviation. The random search algorithm was used to optimize the developed ANN
      models to estimate the optimal values of dietary dLys, dMet, and dThr. The ANN
      models were used to assess the relative importance of each dietary input on the
      bird performance using sensitivity analysis. The statistical evaluations revealed
      the higher accuracy of ANN to predict the bird performance compared with response
      surface methodology models. The optimization results showed that the maximum BW
      gain may be obtained with dietary levels of 1.11, 0.51, and 0.78% of dLys, dMet,
      and dThr, respectively. Minimum feed conversion ratio may be achieved with
      dietary levels of 1.13, 0.54, 0.78% of dLys, dMet, and dThr, respectively. The
      sensitivity analysis on the models indicated that dietary Lys is the most
      important variable in the growth performance of the broiler chicks, followed by
      dietary Thr and Met. The results of this research revealed that the experimental
      data of a response-surface-methodology design could be successfully used to
      develop the well-designed ANN for pattern recognition of bird growth and
      optimization of nutritional requirements. The comparison between the 2 methods
      also showed that the statistical methods may have little effect on the ideal
      ratios of dMet and dThr to dLys in broiler chicks using multivariate
      optimization.

PMID- 23155042
TI  - Predicting body and carcass characteristics of 2 broiler chicken strains using
      support vector regression and neural network models.
AB  - As a new modeling method, support vector regression (SVR) has been regarded as
      the state-of-the-art technique for regression and approximation. In this study,
      the SVR models had been introduced and developed to predict body and carcass
      related characteristics of 2 strains of broiler chicken. To evaluate the
      prediction ability of SVR models, we compared their performance with that of
      neural network (NN) models. Evaluation of the prediction accuracy of models was
      based on the R(2), MS error, and bias. The variables of interest as model output
      were BW, empty BW, carcass, breast, drumstick, thigh, and wing weight in 2
      strains of Ross and Cobb chickens based on intake dietary nutrients, including ME
      (kcal/bird per week), CP, TSAA, and Lys, all as grams per bird per week. A data
      set composed of 64 measurements taken from each strain were used for this
      analysis, where 44 data lines were used for model training, whereas the remaining
      20 lines were used to test the created models. The results of this study revealed
      that it is possible to satisfactorily estimate the BW and carcass parts of the
      broiler chickens via their dietary nutrient intake. Through statistical criteria
      used to evaluate the performance of the SVR and NN models, the overall results
      demonstrate that the discussed models can be effective for accurate prediction of
      the body and carcass-related characteristics investigated here. However, the SVR
      method achieved better accuracy and generalization than the NN method. This
      indicates that the new data mining technique (SVR model) can be used as an
      alternative modeling tool for NN models. However, further reevaluation of this
      algorithm in the future is suggested.

PMID- 23155043
TI  - Assessment of production performance in 2 breeds of broilers fed prebiotics as
      feed additives.
AB  - Pasture-flock-raised poultry are becoming an increasingly popular product, but
      only limited options are currently available for maintaining gut health. For
      these producers, prebiotics are an attractive option because they are generally
      recognized as safe (GRAS) and can be mixed into the feed and thus do not require
      adjustments to production protocols. However, if prebiotic treatments reduce
      production performance, they would not be useful to producers. Thus, the
      objective of this study was to measure performance of pasture-raised broilers fed
      1 of 3 prebiotic treatments. For these trials, 2 breeds of birds were used: Naked
      Neck slow-growing breeds and Cornish White Rock cross fast-growing breeds. The
      experimental design was replicated for each breed. A total of 340 birds were
      split into 4 groups, each group fed one feed additive: 1) galactoligosaccharides
      (2% wt/wt), 2) fructooligosaccharides (1% wt/wt), 3) plum fibers (1% wt/wt), or
      4) no additives. During the 8-wk rearing period, 10 birds from each group were
      collected and euthanized to take small intestine samples. Histological
      preparations were made from the small intestine tissue, and 4 measurements of
      villi height and crypt depth from each cross section were taken. Throughout the
      study, mortality was monitored and BW measurements were taken at 2-wk intervals.
      For the Cornish White Rock cross, the group receiving the feed supplemented with
      fructooligosaccharides had higher (P < 0.05) 8-wk BW than those fed Plum; control
      and birds fed galactoligosaccharides were intermediate. For the Naked Neck breed,
      the group receiving the plum fibers had the highest final BW. It appears that all
      3 feed supplements offered some protective effect for alterations in villi length
      and crypt depth due to feed withdrawal, but only for the Naked Neck breed. The
      data indicate the 3 prebiotics utilized in this study could be used without risk
      of decreasing production performance, but only for Naked Neck breeds.

PMID- 23155044
TI  - Oncogenic Wnt/beta-catenin signalling pathways in the cancer-resistant epididymis
      have implications for cancer research.
AB  - Aberrant activation of the Wnt/beta-catenin pathway occurs in cancers. This
      review presents several important cancer-related aspects of Wnt/beta-catenin
      signalling relevant to the epididymis, provides evidence of such epididymal gene
      expression and suggests a new direction for further research. The data presented
      here indicate that besides containing many Wnt/beta-catenin-pathway components,
      the normal adult human epididymis expresses much more beta-catenin than the
      colorectal carcinoma cell line HCT116, which possesses elevated beta-catenin
      expression. The low cancer incidence in the epididymis may be due to factors
      present in the human epididymis that regulate this oncogenic Wnt/beta-catenin
      pathway, including (i) 14 of 17 secreted pathway inhibitors, (ii) the majority of
      the micro-RNAs known to target this pathway, (iii) plasma membrane-associated E
      cadherin and CEACAM1 that anchor beta-catenin, preventing its availability for
      nuclear entry and oncogenic transcriptional activity, (iv) the recently
      identified membrane-located tumourigenesis inhibitors RNF43 and ZNRF3 that
      mediate the degradation of the Wnt receptor components Fzds and Lrp5/6 and (v)
      nuclear KLF4, which competes with TCF for beta-catenin, limiting its
      transcriptional activity and stabilizing telomeres, thereby reducing mutation
      incidence. The above regulatory factors expressed by the human epididymis, and
      the absence of androgen receptor translocation known to promote nuclear
      translocation of beta-catenin in tumourigenesis in an animal model, may act
      synergistically to provide hostility in different cell compartments towards
      tumour formation. The lack of evidence for beta-catenin in epididymal nuclei is
      noteworthy. Studying this phenomenon may help reveal the mechanisms underlying
      oncogenic Wnt/beta-catenin signalling and shed new light on cancer therapy and
      prevention.

PMID- 23155045
TI  - Diverse roles of strigolactones in plant development.
AB  - With the discovery of strigolactones as root exudate signals that trigger
      parasitic weed seed germination, and then as a branching inhibitor and plant
      hormone, the next phase of strigolactone research has quickly revealed this
      hormone class as a major player in optimizing plant growth and development. From
      the early stages of plant evolution, it seems that strigolactones were involved
      in enabling plants to modify growth in order to gain advantage in competition
      with neighboring organisms for limited resources. For example, a moss plant can
      alter its growth in response to strigolactones emanating from a neighbor. Within
      a higher plant, strigolactones appear to be involved in controlling the balance
      of resource distribution via strategic modification of growth and development.
      Most notably, higher plants that encounter phosphate deficiency increase
      strigolactone production, which changes root growth and promotes fungal symbiosis
      to enhance phosphate intake. The shoot also changes by channeling resources away
      from unessential leaves and branches and into the main stem and root system. This
      hormonal response is a key adaption that radically alters whole-plant
      architecture in order to optimize growth and development under diverse
      environmental conditions.

PMID- 23155046
TI  - Characterization of a small molecule inhibitor of plasminogen activator inhibitor
      type 1 that accelerates the transition into the latent conformation.
AB  - A novel class of small molecule inhibitors for plasminogen activator inhibitor
      type 1 (PAI-1), represented by AZ3976, was identified in a high throughput
      screening campaign. AZ3976 displayed an IC(50) value of 26 MUm in an enzymatic
      chromogenic assay. In a plasma clot lysis assay, the compound was active with an
      IC(50) of 16 MUm. Surprisingly, AZ3976 did not bind to active PAI-1 but bound to
      latent PAI-1 with a K(D) of 0.29 MUm at 35  degrees C and a binding stoichiometry
      of 0.94, as measured by isothermal calorimetry. Reversible binding was confirmed
      by surface plasmon resonance direct binding experiments. The x-ray structure of
      AZ3976 in complex with latent PAI-1 was determined at 2.4 A resolution. The
      inhibitor was bound in the flexible joint region with the entrance to the cavity
      located between alpha-helix D and beta-strand 2A. A set of surface plasmon
      resonance experiments revealed that AZ3976 inhibited PAI-1 by enhancing the
      latency transition of active PAI-1. Because AZ3976 only had measurable affinity
      for latent PAI-1, we propose that its mechanism of inhibition is based on binding
      to a small fraction in equilibrium with active PAI-1, a latent-like prelatent
      form, from which latent PAI-1 is then generated more rapidly. This mode of
      action, with induced accelerated latency transition of active PAI-1 may, together
      with supporting x-ray data, provide improved opportunities for small molecule
      drug design in the hunt for therapeutically useful PAI-1 inhibitors.

PMID- 23155047
TI  - Exposure to a cutinase-like serine esterase triggers rapid lysis of multiple
      mycobacterial species.
AB  - Mycobacteria are shaped by a thick envelope made of an array of uniquely
      structured lipids and polysaccharides. However, the spatial organization of these
      molecules remains unclear. Here, we show that exposure to an esterase from
      Mycobacterium smegmatis (Msmeg_1529), hydrolyzing the ester linkage of trehalose
      dimycolate in vitro, triggers rapid and efficient lysis of Mycobacterium
      tuberculosis, Mycobacterium bovis BCG, and Mycobacterium marinum. Exposure to the
      esterase immediately releases free mycolic acids, while concomitantly depleting
      trehalose mycolates. Moreover, lysis could be competitively inhibited by an
      excess of purified trehalose dimycolate and was abolished by a S124A mutation
      affecting the catalytic activity of the esterase. These findings are consistent
      with an indispensable structural role of trehalose mycolates in the architectural
      design of the exposed surface of the mycobacterial envelope. Importantly, we also
      demonstrate that the esterase-mediated rapid lysis of M. tuberculosis
      significantly improves its detection in paucibacillary samples.

PMID- 23155048
TI  - Mechanical modulation of ATP-binding affinity of V1-ATPase.
AB  - V(1)-ATPase is a rotary motor protein that rotates the central shaft in a
      counterclockwise direction hydrolyzing ATP. Although the ATP-binding process is
      suggested to be the most critical reaction step for torque generation in F(1)
      ATPase (the closest relative of V(1)-ATPase evolutionarily), the role of ATP
      binding for V(1)-ATPase in torque generation has remained unclear. In the present
      study, we performed single-molecule manipulation experiments on V(1)-ATPase from
      Thermus thermophilus to investigate how the ATP-binding process is modulated upon
      rotation of the rotary shaft. When V(1)-ATPase showed an ATP-waiting pause, it
      was stalled at a target angle and then released. Based on the response of the
      V(1)-ATPase released, the ATP-binding probability was determined at individual
      stall angles. It was observed that the rate constant of ATP binding (k(on)) was
      exponentially accelerated with forward rotation, whereas the rate constant of ATP
      release (k(off)) was exponentially reduced. The angle dependence of the k(off) of
      V(1)-ATPase was significantly smaller than that of F(1)-ATPase, suggesting that
      the ATP-binding process is not the major torque-generating step in V(1)-ATPase.
      When V(1)-ATPase was stalled at the mean binding angle to restrict rotary
      Brownian motion, k(on) was evidently slower than that determined from free
      rotation, showing the reaction rate enhancement by conformational fluctuation. It
      was also suggested that shaft of V(1)-ATPase should be rotated at least 277
      degrees  in a clockwise direction for efficient release of ATP under ATP
      synthesis conditions.

PMID- 23155049
TI  - Inhibition of glycogen synthase kinase-3 ameliorates beta-amyloid pathology and
      restores lysosomal acidification and mammalian target of rapamycin activity in
      the Alzheimer disease mouse model: in vivo and in vitro studies.
AB  - Accumulation of beta-amyloid (Abeta) deposits is a primary pathological feature
      of Alzheimer disease that is correlated with neurotoxicity and cognitive decline.
      The role of glycogen synthase kinase-3 (GSK-3) in Alzheimer disease pathogenesis
      has been debated. To study the role of GSK-3 in Abeta pathology, we used 5XFAD
      mice co-expressing mutated amyloid precursor protein and presenilin-1 that
      develop massive cerebral Abeta loads. Both GSK-3 isozymes (alpha/beta) were
      hyperactive in this model. Nasal treatment of 5XFAD mice with a novel substrate
      competitive GSK-3 inhibitor, L803-mts, reduced Abeta deposits and ameliorated
      cognitive deficits. Analyses of 5XFAD hemi-brain samples indicated that L803-mts
      restored the activity of mammalian target of rapamycin (mTOR) and inhibited
      autophagy. Lysosomal acidification was impaired in the 5XFAD brains as indicated
      by reduced cathepsin D activity and decreased N-glycoyslation of the vacuolar
      ATPase subunit V0a1, a modification required for lysosomal acidification.
      Treatment with L803-mts restored lysosomal acidification in 5XFAD brains. Studies
      in SH-SY5Y cells confirmed that GSK-3alpha and GSK-3beta impair lysosomal
      acidification and that treatment with L803-mts enhanced the acidic lysosomal pool
      as demonstrated in LysoTracker Red-stained cells. Furthermore, L803-mts restored
      impaired lysosomal acidification caused by dysfunctional presenilin-1. We provide
      evidence that mTOR is a target activated by GSK-3 but inhibited by impaired
      lysosomal acidification and elevation in amyloid precursor protein/Abeta loads.
      Taken together, our data indicate that GSK-3 is a player in Abeta pathology.
      Inhibition of GSK-3 restores lysosomal acidification that in turn enables
      clearance of Abeta burdens and reactivation of mTOR. These changes facilitate
      amelioration in cognitive function.

PMID- 23155050
TI  - ras-Induced up-regulation of CTP:phosphocholine cytidylyltransferase alpha
      contributes to malignant transformation of intestinal epithelial cells.
AB  - Cancer cells have enhanced lipogenic capacity characterized by increased
      synthesis of fatty acids and complex lipids, including phosphatidylcholine (PC).
      As the rate-limiting enzyme in the CDP-choline pathway for PC synthesis,
      CTP:phosphocholine cytidylyltransferase alpha (CCTalpha) is implicated in the
      provision of membranes and bioactive lipids necessary of cell proliferation. In
      this study, we assessed the role of CCTalpha in malignant intestinal epithelial
      cells transformed with activated H-ras (IEC-ras). Three IEC-ras clones had
      significant up-regulation CCTalpha expression, but PC synthesis and in vitro
      activity of CCTalpha were similar to control IEC. RNA interference of CCTalpha in
      adherent IEC-ras did not affect PC synthesis, confirming that the enzyme was
      relatively inactive. However, CCTalpha silencing in ras-transformed IEC reduced
      anchorage-independent growth, a criterion for malignant transformation, as well
      as tumorigenicity in mice. Relative to their adherent counterparts, detached IEC
      ras had increased PC synthesis that was attenuated by inducible CCTalpha
      silencing. Detachment of IEC-ras was accompanied by increased CCTalpha
      phosphorylation and cytosolic enzyme activity. We conclude that the expanded pool
      of CCTalpha in IEC-ras is activated by detachment. This provides the increased PC
      biosynthetic capacity that contributes to malignant transformation of intestinal
      epithelial cells when detached from the extracellular matrix.

PMID- 23155051
TI  - The retinol dehydrogenase Rdh10 localizes to lipid droplets during acyl ester
      biosynthesis.
AB  - Rdh10 catalyzes the first step of all-trans-retinoic acid biogenesis
      physiologically, conversion of retinol into retinal. We show that Rdh10
      associates predominantly with mitochondria/mitochondrial-associated membrane
      (MAM) in the absence of lipid droplet biosynthesis, but also locates with lipid
      droplets during acyl ester biosynthesis. Targeting to lipid droplets requires the
      32 N-terminal residues, which include a hydrophobic region followed by a net
      positive charge. Targeting to mitochondria/MAM and/or the stability of Rdh10
      require both the N-terminal and the 48 C-terminal hydrophobic residues. Rdh10
      behaves similarly to cellular retinol-binding protein, type 1, which also
      localizes to mitochondria/MAM before lipid droplet synthesis, and associates with
      lipid droplets during acyl ester synthesis (Jiang, W., and Napoli, J. L. (2012)
      Biochem. Biophys. Acta 1820, 859-8692). LRAT, an ER protein, also associates with
      lipid droplets upon acyl ester biosynthesis. Colocalization of Rdh10, Crbp1, and
      LRAT on lipid droplets suggests a metabolon that mediates retinol homeostasis.

PMID- 23155052
TI  - Matrix metalloproteinase-1-mediated up-regulation of vascular endothelial growth
      factor-2 in endothelial cells.
AB  - Matrix metalloproteinase-1 (MMP-1) is a collagenase that is highly active in
      extracellular matrix and vascular remodeling, angiogenesis, and tumor
      progression. Vascular endothelial growth factor receptor-2 (VEGFR2), the main
      receptor for VEGF-A, is expressed on endothelial cells and promotes cell
      survival, proliferation, and other functions. Although MMP-1 and VEGFR2 co-exist
      in many normal and pathophysiological conditions, the effect of MMP-1 on cellular
      VEGFR2 that can promote the above processes is unknown. In this study we test the
      hypothesis that stimulation of endothelial cells with MMP-1 increases their
      levels of VEGFR2. The increased VEGFR2 is then available to bind VEGF-A,
      resulting in increased response. Indeed we found that endothelial cells incubated
      with active MMP-1 had higher mRNA and protein levels of VEGFR2. Furthermore, VEGF
      A-dependent phosphorylation of intracellular signaling molecules and endothelial
      proliferation were elevated after MMP-1 treatment. MMP-1 caused activation of the
      nuclear factor-kappaB (NF-kappaB) pathway (p65/RelA) in endothelial cells, and
      this response was dependent upon activation of protease activated receptor-1 (PAR
      1). Chromatin immunoprecipitation was used to confirm NF-kappaB-mediated active
      transcription of the VEGFR2 (KDR) gene. Elevation in VEGFR2 after MMP-1
      stimulation was inhibited by PAR-1 knockdown and NF-kappaB specific inhibition.
      We conclude that MMP-1 promotes VEGFR2 expression and proliferation of
      endothelial cells through stimulation of PAR-1 and activation of NF-kappaB. These
      results suggest a mechanism by which MMP-1 may prime or sensitize endothelial
      cell functions.

PMID- 23155053
TI  - Integration and long distance axonal regeneration in the central nervous system
      from transplanted primitive neural stem cells.
AB  - Spinal cord injury (SCI) results in devastating motor and sensory deficits
      secondary to disrupted neuronal circuits and poor regenerative potential. Efforts
      to promote regeneration through cell extrinsic and intrinsic manipulations have
      met with limited success. Stem cells represent an as yet unrealized therapy in
      SCI. Recently, we identified novel culture methods to induce and maintain
      primitive neural stem cells (pNSCs) from human embryonic stem cells. We tested
      whether transplanted human pNSCs can integrate into the CNS of the developing
      chick neural tube and injured adult rat spinal cord. Following injection of pNSCs
      into the developing chick CNS, pNSCs integrated into the dorsal aspects of the
      neural tube, forming cell clusters that spontaneously differentiated into
      neurons. Furthermore, following transplantation of pNSCs into the lesioned rat
      spinal cord, grafted pNSCs survived, differentiated into neurons, and extended
      long distance axons through the scar tissue at the graft-host interface and into
      the host spinal cord to form terminal-like structures near host spinal neurons.
      Together, these findings suggest that pNSCs derived from human embryonic stem
      cells differentiate into neuronal cell types with the potential to extend axons
      that associate with circuits of the CNS and, more importantly, provide new
      insights into CNS integration and axonal regeneration, offering hope for repair
      in SCI.

PMID- 23155054
TI  - Characterization of the enzyme CbiH60 involved in anaerobic ring contraction of
      the cobalamin (vitamin B12) biosynthetic pathway.
AB  - The anaerobic pathway for the biosynthesis of cobalamin (vitamin B(12)) has
      remained poorly characterized because of the sensitivity of the pathway
      intermediates to oxygen and the low activity of enzymes. One of the major
      bottlenecks in the anaerobic pathway is the ring contraction step, which has not
      been observed previously with a purified enzyme system. The Gram-positive aerobic
      bacterium Bacillus megaterium has a complete anaerobic pathway that contains an
      unusual ring contraction enzyme, CbiH(60), that harbors a C-terminal extension
      with sequence similarity to the nitrite/sulfite reductase family. To improve
      solubility, the enzyme was homologously produced in the host B. megaterium
      DSM319. CbiH(60) was characterized by electron paramagnetic resonance and shown
      to contain a [4Fe-4S] center. Assays with purified recombinant CbiH(60)
      demonstrate that the enzyme converts both cobalt-precorrin-3 and cobalt factor
      III into the ring-contracted product cobalt-precorrin-4 in high yields, with the
      latter transformation dependent upon DTT and an intact Fe-S center. Furthermore,
      the ring contraction process was shown not to involve a change in the oxidation
      state of the central cobalt ion of the macrocycle.

PMID- 23155056
TI  - Structural insights into the stability perturbations induced by N-terminal
      variation in human and goat alpha-lactalbumin.
AB  - Addition of an extra methionine at the N-terminus by recombinant expression of
      alpha-lactalbumin in Escherichia coli significantly destabilizes the protein, and
      this destabilization has hampered mutational analyses such as the mutational phi
      value analysis of the protein. Deletion of residue 1 from the recombinant form
      recovers the stability in human and goat alpha-lactalbumin. Here, we thus
      determined the crystal structures of the residue 1-deletion variants of
      recombinant human and goat alpha-lactalbumin, and compared the structures with
      those of the authentic and recombinant forms. The results demonstrate the
      importance of the N-terminal backbone structure and hydrogen-bonding pattern for
      the stability of alpha-lactalbumin.

PMID- 23155055
TI  - In vivo phosphorylation of Ser21 and Ser83 during nutrient-induced activation of
      the yeast protein kinase A (PKA) target trehalase.
AB  - The readdition of an essential nutrient to starved, fermenting cells of the yeast
      Saccharomyces cerevisiae triggers rapid activation of the protein kinase A (PKA)
      pathway. Trehalase is activated 5-10-fold within minutes and has been used as a
      convenient reporter for rapid activation of PKA in vivo. Although trehalase can
      be phosphorylated and activated by PKA in vitro, demonstration of phosphorylation
      during nutrient activation in vivo has been lacking. We now show, using
      phosphospecific antibodies, that glucose and nitrogen activation of trehalase in
      vivo is associated with phosphorylation of Ser(21) and Ser(83). Unexpectedly,
      mutants with reduced PKA activity show constitutive phosphorylation despite
      reduced trehalase activation. The same phenotype was observed upon deletion of
      the catalytic subunits of yeast protein phosphatase 2A, suggesting that lower PKA
      activity causes reduced trehalase dephosphorylation. Hence, phosphorylation of
      trehalase in vivo is not sufficient for activation. Deletion of the inhibitor
      Dcs1 causes constitutive trehalase activation and phosphorylation. It also
      enhances binding of trehalase to the 14-3-3 proteins Bmh1 and Bmh2, suggesting
      that Dcs1 inhibits by preventing 14-3-3 binding. Deletion of Bmh1 and Bmh2
      eliminates both trehalase activation and phosphorylation. Our results reveal that
      trehalase activation in vivo is associated with phosphorylation of typical PKA
      sites and thus establish the enzyme as a reliable read-out for nutrient
      activation of PKA in vivo.

PMID- 23155057
TI  - Engineering of alpha1-antitrypsin variants with improved specificity for the
      proprotein convertase furin using site-directed random mutagenesis.
AB  - Furin, PACE4, PC5/6 and PC7 are members of the subtilisin-like proprotein
      convertase (SPC) family. Although these enzymes are known to play critical roles
      in various physiological and pathological events including cell differentiation,
      tumor growth, virus replication and the activation of bacterial toxins, their
      distinct functions are yet to be fully delineated. alpha1-PDX is an engineered
      alpha1-antitrypsin variant carrying the RXXR consensus motif for furin within its
      reactive site loop. However, alpha1-PDX inhibits other SPCs in addition to furin.
      In this work, we prepared various rat alpha1-antitrypsin variants containing Arg
      at the P1 site within the reactive site loop, and examined their respective
      selectivity. The novel alpha1-antitrypsin variant AVNR (AVPM(352)/AVNR) was
      identified as a highly selective inhibitor of furin. This variant formed a sodium
      dodecyl sulfate- and heat-stable furin/alpha1-antitrypsin complex and inhibited
      furin activity ex vivo and in vitro. Other SPC members including PACE4, PC5/6 and
      PC7 were not inhibited by the AVNR variant. Furin-mediated maturation of bone
      morphogenetic protein-4 was completely inhibited by ectopic expression of the
      AVNR variant. The AVNR variant should prove to be a useful inhibitor in
      identifying the specific role of furin.

PMID- 23155058
TI  - 'Lung cancer and tobacco consumption': technical evaluation of the 1943 paper by
      Schairer and Schoeniger published in Nazi Germany.

PMID- 23155059
TI  - Totally drug-resistant tuberculosis (TDR-TB) in India: every dark cloud has a
      silver lining.

PMID- 23155060
TI  - On the usefulness of ontologies in epidemiology research and practice.

PMID- 23155061
TI  - RNApathwaysDB--a database of RNA maturation and decay pathways.
AB  - Many RNA molecules undergo complex maturation, involving e.g. excision from
      primary transcripts, removal of introns, post-transcriptional modification and
      polyadenylation. The level of mature, functional RNAs in the cell is controlled
      not only by the synthesis and maturation but also by degradation, which proceeds
      via many different routes. The systematization of data about RNA metabolic
      pathways and enzymes taking part in RNA maturation and degradation is essential
      for the full understanding of these processes. RNApathwaysDB, available online at
      http://iimcb.genesilico.pl/rnapathwaysdb, is an online resource about maturation
      and decay pathways involving RNA as the substrate. The current release presents
      information about reactions and enzymes that take part in the maturation and
      degradation of tRNA, rRNA and mRNA, and describes pathways in three model
      organisms: Escherichia coli, Saccharomyces cerevisiae and Homo sapiens.
      RNApathwaysDB can be queried with keywords, and sequences of protein enzymes
      involved in RNA processing can be searched with BLAST. Options for data
      presentation include pathway graphs and tables with enzymes and literature data.
      Structures of macromolecular complexes involving RNA and proteins that act on it
      are presented as 'potato models' using DrawBioPath-a new javascript tool.

PMID- 23155062
TI  - Crenarchaeal chromatin proteins Cren7 and Sul7 compact DNA by inducing rigid
      bends.
AB  - Archaeal chromatin proteins share molecular and functional similarities with both
      bacterial and eukaryotic chromatin proteins. These proteins play an important
      role in functionally organizing the genomic DNA into a compact nucleoid. Cren7
      and Sul7 are two crenarchaeal nucleoid-associated proteins, which are
      structurally homologous, but not conserved at the sequence level. Co-crystal
      structures have shown that these two proteins induce a sharp bend on binding to
      DNA. In this study, we have investigated the architectural properties of these
      proteins using atomic force microscopy, molecular dynamics simulations and
      magnetic tweezers. We demonstrate that Cren7 and Sul7 both compact DNA molecules
      to a similar extent. Using a theoretical model, we quantify the number of
      individual proteins bound to the DNA as a function of protein concentration and
      show that forces up to 3.5 pN do not affect this binding. Moreover, we
      investigate the flexibility of the bending angle induced by Cren7 and Sul7 and
      show that the protein-DNA complexes differ in flexibility from analogous
      bacterial and eukaryotic DNA-bending proteins.

PMID- 23155063
TI  - The UCSC Genome Browser database: extensions and updates 2013.
AB  - The University of California Santa Cruz (UCSC) Genome Browser
      (http://genome.ucsc.edu) offers online public access to a growing database of
      genomic sequence and annotations for a wide variety of organisms. The Browser is
      an integrated tool set for visualizing, comparing, analysing and sharing both
      publicly available and user-generated genomic datasets. As of September 2012,
      genomic sequence and a basic set of annotation 'tracks' are provided for 63
      organisms, including 26 mammals, 13 non-mammal vertebrates, 3 invertebrate
      deuterostomes, 13 insects, 6 worms, yeast and sea hare. In the past year 19 new
      genome assemblies have been added, and we anticipate releasing another 28 in
      early 2013. Further, a large number of annotation tracks have been either added,
      updated by contributors or remapped to the latest human reference genome. Among
      these are an updated UCSC Genes track for human and mouse assemblies. We have
      also introduced several features to improve usability, including new navigation
      menus. This article provides an update to the UCSC Genome Browser database, which
      has been previously featured in the Database issue of this journal.

PMID- 23155064
TI  - MetalPDB: a database of metal sites in biological macromolecular structures.
AB  - We present here MetalPDB (freely accessible at http://metalweb.cerm.unifi.it), a
      novel resource aimed at conveying the information available on the three
      dimensional (3D) structures of metal-binding biological macromolecules in a
      consistent and effective manner. This is achieved through the systematic and
      automated representation of metal-binding sites in proteins and nucleic acids by
      way of Minimal Functional Sites (MFSs). MFSs are 3D templates that describe the
      local environment around the metal(s) independently of the larger context of the
      macromolecular structure embedding the site(s), and are the central objects of
      MetalPDB design. MFSs are grouped into equistructural (broadly defined as sites
      found in corresponding positions in similar structures) and equivalent sites
      (equistructural sites that contain the same metals), allowing users to easily
      analyse similarities and variations in metal-macromolecule interactions, and to
      link them to functional information. The web interface of MetalPDB allows access
      to a comprehensive overview of metal-containing biological structures, providing
      a basis to investigate the basic principles governing the properties of these
      systems. MetalPDB is updated monthly in an automated manner.

PMID- 23155065
TI  - A versatile cis-blocking and trans-activation strategy for ribozyme
      characterization.
AB  - Synthetic RNA control devices that use ribozymes as gene-regulatory components
      have been applied to controlling cellular behaviors in response to environmental
      signals. Quantitative measurement of the in vitro cleavage rate constants
      associated with ribozyme-based devices is essential for advancing the molecular
      design and optimization of this class of gene-regulatory devices. One of the key
      challenges encountered in ribozyme characterization is the efficient generation
      of full-length RNA from in vitro transcription reactions, where conditions
      generally lead to significant ribozyme cleavage. Current methods for generating
      full-length ribozyme-encoding RNA rely on a trans-blocking strategy, which
      requires a laborious gel separation and extraction step. Here, we develop a
      simple two-step gel-free process including cis-blocking and trans-activation
      steps to support scalable generation of functional full-length ribozyme-encoding
      RNA. We demonstrate our strategy on various types of natural ribozymes and
      synthetic ribozyme devices, and the cleavage rate constants obtained for the RNA
      generated from our strategy are comparable with those generated through
      traditional methods. We further develop a rapid, label-free ribozyme cleavage
      assay based on surface plasmon resonance, which allows continuous, real-time
      monitoring of ribozyme cleavage. The surface plasmon resonance-based
      characterization assay will complement the versatile cis-blocking and trans
      activation strategy to broadly advance our ability to characterize and engineer
      ribozyme-based devices.

PMID- 23155066
TI  - DiffSplice: the genome-wide detection of differential splicing events with RNA
      seq.
AB  - The RNA transcriptome varies in response to cellular differentiation as well as
      environmental factors, and can be characterized by the diversity and abundance of
      transcript isoforms. Differential transcription analysis, the detection of
      differences between the transcriptomes of different cells, may improve
      understanding of cell differentiation and development and enable the
      identification of biomarkers that classify disease types. The availability of
      high-throughput short-read RNA sequencing technologies provides in-depth sampling
      of the transcriptome, making it possible to accurately detect the differences
      between transcriptomes. In this article, we present a new method for the
      detection and visualization of differential transcription. Our approach does not
      depend on transcript or gene annotations. It also circumvents the need for full
      transcript inference and quantification, which is a challenging problem because
      of short read lengths, as well as various sampling biases. Instead, our method
      takes a divide-and-conquer approach to localize the difference between
      transcriptomes in the form of alternative splicing modules (ASMs), where
      transcript isoforms diverge. Our approach starts with the identification of ASMs
      from the splice graph, constructed directly from the exons and introns predicted
      from RNA-seq read alignments. The abundance of alternative splicing isoforms
      residing in each ASM is estimated for each sample and is compared across sample
      groups. A non-parametric statistical test is applied to each ASM to detect
      significant differential transcription with a controlled false discovery rate.
      The sensitivity and specificity of the method have been assessed using simulated
      data sets and compared with other state-of-the-art approaches. Experimental
      validation using qRT-PCR confirmed a selected set of genes that are
      differentially expressed in a lung differentiation study and a breast cancer data
      set, demonstrating the utility of the approach applied on experimental biological
      data sets. The software of DiffSplice is available at
      http://www.netlab.uky.edu/p/bioinfo/DiffSplice.

PMID- 23155067
TI  - Purification of DNA-origami nanostructures by rate-zonal centrifugation.
AB  - Most previously reported methods for purifying DNA-origami nanostructures rely on
      agarose-gel electrophoresis (AGE) for separation. Although AGE is routinely used
      to yield 0.1-1 ug purified DNA nanostructures, obtaining >100 ug of purified DNA
      origami structure through AGE is typically laborious because of the post
      electrophoresis extraction, desalting and concentration steps. Here, we present a
      readily scalable purification approach utilizing rate-zonal centrifugation, which
      provides comparable separation resolution as AGE. The DNA nanostructures remain
      in aqueous solution throughout the purification process. Therefore, the desired
      products are easily recovered with consistently high yield (40-80%) and without
      contaminants such as residual agarose gel or DNA intercalating dyes. Seven
      distinct three-dimensional DNA-origami constructs were purified at the scale of
      0.1-100 ug (final yield) per centrifuge tube, showing the versatility of this
      method. Given the commercially available equipment for gradient mixing and
      fraction collection, this method should be amenable to automation and further
      scale up for preparation of larger amounts (e.g. milligram quantities) of DNA
      nanostructures.

PMID- 23155077
TI  - Ocular disease in working horses in Ethiopia: a cross-sectional study.
AB  - Ocular disease is a frequent finding in working horses. This study aimed to
      estimate the prevalence and types of ocular pathology, and explore risk factors
      potentially associated with disease within a population of working horses in
      Ethiopia. In total, 1049 horses were selected from horses attending clinics run
      by the Society for Protection of Animals Abroad (SPANA). Each had an ophthalmic
      examination conducted under field conditions using a pen-torch. All owners
      completed a short questionnaire. The prevalence of ocular abnormalities was 23.5
      per cent (95 per cent confidence interval (CI) 18.0 per cent to 30.1 per cent)
      and the percentage of horses with an abnormality in at least one eye was 43 per
      cent (95 per cent CI 28.7 per cent to 58.4 per cent), although this varied
      between towns. Mild eye pathology and end-stage disease with irreversible
      pathology were most common. There were significantly more eye abnormalities in
      the right eye compared with the left, and older horses were more likely to have
      ocular pathology. Only 55.1 per cent of owners had noticed there was an ocular
      abnormality present, and only 2.2 per cent had received any previous treatment
      for eye disease. Only 1.9 per cent presented to the clinic because of an eye
      problem. There appears to be either a lack of owner awareness, or a low
      perception of the importance of eye disease among owners.

PMID- 23155078
TI  - Serotonergic and cholinergic elements of the hypoxic ventilatory response in
      developing zebrafish.
AB  - The chemosensory roles of gill neuroepithelial cells (NECs) in mediating the
      hyperventilatory response to hypoxia are not clearly defined in fish. While
      serotonin (5-HT) is the predominant neurotransmitter in O(2)-sensitive gill NECs,
      acetylcholine (ACh) plays a more prominent role in O(2) sensing in terrestrial
      vertebrates. The present study characterized the developmental chronology of
      potential serotonergic and cholinergic chemosensory pathways of the gill in the
      model vertebrate, the zebrafish (Danio rerio). In immunolabelled whole gills from
      larvae, serotonergic NECs were observed in epithelia of the gill filaments and
      gill arches, while non-serotonergic NECs were found primarily in the gill arches.
      Acclimation of developing zebrafish to hypoxia (P(O2)=75 mmHg) reduced the number
      of serotonergic NECs observed at 7 days post-fertilization (d.p.f.), and this
      effect was absent at 10 d.p.f. In vivo administration of 5-HT mimicked hypoxia by
      increasing ventilation frequency (f(V)) in early stage (7-10 d.p.f.) and late
      stage larvae (14-21 d.p.f.), while ACh increased f(V) only in late stage larvae.
      In time course experiments, application of ketanserin inhibited the
      hyperventilatory response to acute hypoxia (P(O2)=25 mmHg) at 10 d.p.f., while
      hexamethonium did not have this effect until 12 d.p.f. Cells immunoreactive for
      the vesicular acetylcholine transporter (VAChT) began to appear in the gill
      filaments by 14 d.p.f. Characterization in adult gills revealed that VAChT
      positive cells were a separate population of neurosecretory cells of the gill
      filaments. These studies suggest that serotonergic and cholinergic pathways in
      the zebrafish gill develop at different times and contribute to the
      hyperventilatory response to hypoxia.

PMID- 23155079
TI  - Mechanical and energetic scaling relationships of running gait through ontogeny
      in the ostrich (Struthio camelus).
AB  - It is unclear whether small animals, with their high stride frequency and
      crouched posture, or large animals, with more tendinous limbs, are more reliant
      on storage and return of elastic energy during locomotion. The ostrich has a limb
      structure that appears to be adapted for high-speed running with long tendons and
      short muscle fibres. Here we investigate biomechanics of ostrich gait through
      growth and, with consideration of anatomical data, identify scaling relationships
      with increasing body size, relating to forces acting on the musculoskeletal
      structures, effective mechanical advantage (EMA) and mechanical work. Kinematic
      and kinetic data were collected through growth from running ostriches. Joint
      moments scaled in a similar way to the pelvic limb segments as a result of
      consistent posture through growth, such that EMA was independent of body mass.
      Because no postural change was observed, relative loads applied to
      musculoskeletal tissues would be predicted to increase during growth, with
      greater muscle, and hence tendon, load allowing increased potential for elastic
      energy storage with increasing size. Mass-specific mechanical work per unit
      distance was independent of body mass, resulting in a small but significant
      increase in the contribution of elastic energy storage to locomotor economy in
      larger ostriches.

PMID- 23155080
TI  - Shelter availability, stress level and digestive performance in the aspic viper.
AB  - The lack of shelter can perturb behaviors, increase stress level and thus alter
      physiological performance (e.g. digestive, immune or reproductive functions).
      Although intuitive, such potential impacts of lack of shelter remain poorly
      documented. We manipulated shelter availability and environmental and
      physiological variables (i.e. access to a heat source, predator attack, feeding
      status) in a viviparous snake, and assessed sun-basking behavior, digestive
      performance (i.e. digestive transit time, crude estimate of assimilation,
      regurgitation rate) and plasma corticosterone levels (a proxy of stress level).
      Shelter deprivation provoked a strong increase in sun-basking behavior and thus
      elevated body temperature, even in unfed individuals for which energy savings
      would have been otherwise beneficial. The lack of heat was detrimental to
      digestive performance; simulated predator attacks worsened the situation and
      entailed a further deterioration of digestion. The combination of the lack of
      shelter with cool ambient temperatures markedly elevated basal corticosterone
      level and was associated with low digestive performance. This hormonal effect was
      absent when only one negative factor was involved, suggesting a threshold
      response. Overall, our results revealed important non-linear cascading impacts of
      shelter availability on stress-hormone levels, behaviors and physiological
      performance. These results infer that shelter availability is important for
      laboratory studies, captive husbandry and possibly conservation plans.

PMID- 23155081
TI  - Iodine accumulation in sea urchin larvae is dependent on peroxide.
AB  - Iodine has many important biological functions and its concentrations vary with
      the environment. Recent research has provided novel insights into iodine uptake
      mechanisms in marine bacteria and kelp through hydrogen peroxide-dependent
      diffusion (PDD). This mechanism is distinct from sodium-dependent mechanisms
      known from vertebrates. In vertebrates, iodine accumulates in the thyroid gland
      by the action of the apical iodide transporter (AIT) and the sodium/iodide
      symporter (NIS). Neither of these proteins has, thus far, been identified outside
      of the chordates, and PDD (as an iodine uptake mechanism) has never been studied
      in animals. Using (125)I as a marker for total iodine influx, we tested iodine
      uptake via sodium-dependent transport versus PDD in embryos and larvae of the sea
      urchin Strongylocentrotus purpuratus. We found that iodine uptake in S.
      purpuratus is largely independent of NIS/AIT. Instead, we found that uptake is
      dependent on the presence and production of hydrogen peroxide, indicating that
      sea urchin larvae use PDD as a mechanism for iodine acquisition. Our data, for
      the first time, provide conclusive evidence for this mechanism in an animal.
      Furthermore, our data provide preliminary evidence that sodium-dependent iodine
      uptake via active transporter proteins is a synapomorphy of vertebrates.

PMID- 23155083
TI  - Temperature-dependent behaviours are genetically variable in the nematode
      Caenorhabditis briggsae.
AB  - Temperature-dependent behaviours in Caenorhabditis elegans, such as thermotaxis
      and isothermal tracking, are complex behavioural responses that integrate
      sensation, foraging and learning, and have driven investigations to discover many
      essential genetic and neural pathways. The ease of manipulation of the
      Caenorhabditis model system also has encouraged its application to comparative
      analyses of phenotypic evolution, particularly contrasts of the classic model C.
      elegans with C. briggsae. And yet few studies have investigated natural genetic
      variation in behaviour in any nematode. Here we measure thermotaxis and
      isothermal tracking behaviour in genetically distinct strains of C. briggsae,
      further motivated by the latitudinal differentiation in C. briggsae that is
      associated with temperature-dependent fitness differences in this species. We
      demonstrate that C. briggsae performs thermotaxis and isothermal tracking largely
      similar to that of C. elegans, with a tendency to prefer its rearing temperature.
      Comparisons of these behaviours among strains reveal substantial heritable
      natural variation within each species that corresponds to three general patterns
      of behavioural response. However, intraspecific genetic differences in thermal
      behaviour often exceed interspecific differences. These patterns of temperature
      dependent behaviour motivate further development of C. briggsae as a model system
      for dissecting the genetic underpinnings of complex behavioural traits.

PMID- 23155082
TI  - Dietary composition regulates Drosophila mobility and cardiac physiology.
AB  - The impact of dietary composition on exercise capacity is a subject of intense
      study in both humans and model organisms. Interactions between diet and genetics
      are a crucial component of optimized dietary design. However, the genetic factors
      governing exercise response are still not well understood. The recent development
      of invertebrate models for endurance exercise is likely to facilitate study
      designs examining the conserved interactions between diet, exercise and genetics.
      As a first step, we used the Drosophila model to describe the effects of varying
      dietary composition on several physiological indices, including fatigue tolerance
      and climbing speed, cardiac performance, lipid storage and autophagy. We found
      that flies of two divergent genetic backgrounds optimize endurance and cardiac
      performance on relatively balanced low calorie diets. When flies are provided
      with unbalanced diets, diets higher in sugar than in yeast facilitate greater
      endurance at the expense of cardiac performance. Importantly, we found that
      dietary composition has a profound effect on various physiological indices,
      whereas total caloric intake per se has very little predictive value for
      performance. We also found that the effects of diet on endurance are completely
      reversible within 48 h if flies are switched to a different diet.

PMID- 23155084
TI  - Jumping mechanisms of treehopper insects (Hemiptera, Auchenorrhyncha,
      Membracidae).
AB  - The kinematics and jumping performance of treehoppers (Hemiptera,
      Auchenorrhyncha, Membracidae) were analysed from high speed images. The eight
      species analysed had an 11-fold range of body mass (3.8-41 mg) and a 2-fold range
      of body length (4.1-8.4 mm). Body shape was dominated by a prothoracic helmet
      that projected dorsally and posteriorly over the body, and in some species
      forwards to form a protruding horn. Jumping was propelled by rapid depression of
      the trochantera of the hindlegs. The hindlegs were only 30-60% longer than the
      front and middle legs, and 47-94% the length of the body in different species.
      They were slung beneath the body and moved together in the same plane. In
      preparation for a jump, the hindlegs were initially levated and rotated forwards
      so that the femora were pressed into indentations of the coxae. The tibiae were
      flexed about the femora and the tarsi were placed on the ground directly beneath
      the lateral edges of the abdomen. Movements of the front and middle legs adjusted
      the angle of the body relative to the ground, but for most treehoppers this angle
      was small, so that the body was almost parallel to the ground. The rapid
      depression of the hindlegs accelerated the body to take-off in 1.2 ms in the
      lighter treehoppers and 3.7 ms in the heavier ones. Take-off velocities of 2.1
      2.7 m s(-1) were achieved and were not correlated with body mass. In the best
      jumps, these performances involved accelerations of 560-2450 m s(-2) (g forces of
      47-250), an energy expenditure of 13.5-101 MUJ, a power output of 12-32 mW and
      exerted a force of 9.5-29 mN. The power output per mass of muscle far exceeds the
      maximum active contractile limit of normal muscle. Such requirements indicate
      that treehoppers must be using a power amplification mechanism in a catapult-like
      action. Some jumps were preceded by flapping movements of the wings, but the
      propulsive movements of the hindlegs were crucial in achieving take-off.

PMID- 23155085
TI  - Multivariate analysis of behavioural response experiments in humpback whales
      (Megaptera novaeangliae).
AB  - The behavioural response study (BRS) is an experimental design used by field
      biologists to determine the function and/or behavioural effects of conspecific,
      heterospecific or anthropogenic stimuli. When carrying out these studies in
      marine mammals it is difficult to make basic observations and achieve sufficient
      samples sizes because of the high cost and logistical difficulties. Rarely are
      other factors such as social context or the physical environment considered in
      the analysis because of these difficulties. This paper presents results of a BRS
      carried out in humpback whales to test the response of groups to one recording of
      conspecific social sounds and an artificially generated tone stimulus.
      Experiments were carried out in September/October 2004 and 2008 during the
      humpback whale southward migration along the east coast of Australia. In total,
      13 'tone' experiments, 15 'social sound' experiments (using one recording of
      social sounds) and three silent controls were carried out over two field seasons.
      The results (using a mixed model statistical analysis) suggested that humpback
      whales responded differently to the two stimuli, measured by changes in course
      travelled and dive behaviour. Although the response to 'tones' was consistent, in
      that groups moved offshore and surfaced more often (suggesting an aversion to the
      stimulus), the response to 'social sounds' was highly variable and dependent upon
      the composition of the social group. The change in course and dive behaviour in
      response to 'tones' was found to be related to proximity to the source, the
      received signal level and signal-to-noise ratio (SNR). This study demonstrates
      that the behavioural responses of marine mammals to acoustic stimuli are complex.
      In order to tease out such multifaceted interactions, the number of replicates
      and factors measured must be sufficient for multivariate analysis.

PMID- 23155086
TI  - Cellular damage as induced by high temperature is dependent on rate of
      temperature change - investigating consequences of ramping rates on molecular and
      organismal phenotypes in Drosophila melanogaster.
AB  - Ecological relevance and repeatability of results obtained in different
      laboratories are key issues when assessing thermal tolerance of ectotherms.
      Traditionally, assays have used acute exposures to extreme temperatures. The
      outcomes of ecologically more relevant ramping experiments, however, are
      dependent on the rate of temperature change leading to uncertainty of the causal
      factor for loss of function. Here, we test the physiological consequences of
      exposing female Drosophila melanogaster to gradually increasing temperatures in
      so-called ramping assays. We exposed flies to ramping at rates of 0.06 and 0.1
      degrees C min(-1), respectively. Flies were sampled from the two treatments at
      28, 30, 32, 34, 36 and 38 degrees C and tested for heat tolerance and expression
      levels of the heat shock genes hsp23 and hsp70, as well as Hsp70 protein. Heat
      shock genes were upregulated more with a slow compared with a faster ramping
      rate, and heat knock-down tolerance was higher in flies exposed to the faster
      rate. The fact that slow ramping induces a stronger stress response (Hsp
      expression) compared with faster ramping suggests that slow ramping induces more
      heat damage at the cellular level due to longer exposure time. This is supported
      by the observation that fast ramped flies have higher heat knock-down tolerance.
      Thus we observed both accumulation of thermal damage at the molecular level and
      heat hardening at the phenotypic level as a consequence of heat exposure. The
      balance between these processes is dependent on ramping rate leading to the
      observed variation in thermal tolerance when using different rates.

PMID- 23155087
TI  - Sperm metabolism in pigs: a role for peroxisome proliferator-activated receptor
      gamma (PPARgamma).
AB  - Peroxisome proliferator-activated receptor gamma (PPARgamma) is a nuclear hormone
      receptor expressed predominantly in adipose tissue, also implicated in energy
      homeostasis. In this study, we used western blotting and immunofluorescence
      techniques to demonstrate for the first time that pig spermatozoa express
      PPARgamma. To investigate the functional role of PPARgamma in pig sperm, we
      evaluated its action on different events that characterize the biology of sperm
      cells, i.e. motility, capacitation, viability and acrosome reaction, using the
      PPARgamma-agonist 15-deoxy-12,14-prostaglandin J2 (PGJ2). In responses to PGJ2
      treatment, motility, cholesterol efflux and tyrosine phosphorylation were
      increased, which broadens the role of PPARgamma from that previously described in
      the literature, as it also acts to improve sperm functionality. To further our
      understanding of the significance of PPARgamma in pig sperm, we focused its
      effects on lipid and glucose metabolism. Evaluation of triglyceride content and
      lipase, acyl-CoA dehydrogenase and G6PDH activities suggests that PPARgamma
      induces energy expenditure in pig spermatozoa. These data represent a meaningful
      advance in the field of sperm energy metabolism. Taken together, our results
      demonstrate for the first time that PPARgamma is expressed by pig sperm, thus
      improving its functionalities in terms of motility, capacitation, acrosome
      reaction, survival and metabolism.

PMID- 23155089
TI  - Enhanced erythropoiesis in mice exposed to low environmental temperature.
AB  - Hematopoietic responses to environmental factors are not fully characterized.
      Polycythemia has been reported during exposure to low temperatures in ectothermic
      animals. The relationship between the causes of polycythemia and erythropoiesis
      during low temperature exposure is not fully understood. In this study, we
      exposed C57BL/6 mice to 5 degrees C and monitored the blood cell counts and
      erythropoiesis. The hematocrit level increased from 45.6 to 52.2% after 14 days.
      Likewise, the hemoglobin concentration, initially 15.1 g dl(-1), rose to 16.0 g
      dl(-1). The reticulocyte production index significantly increased from 4 to 8%
      after 7 days. We examined the anatomy and cell composition of the spleens of the
      mice. On day 5, the spleens were ~6 mg g(-1) of body mass, which was twofold
      greater than the spleens on day 0. Flow cytometry showed fourfold more
      proerythroblasts on day 5, compared with day 0. Additionally, the number of late
      stage mature erythroblasts increased on day 14. Erythropoietin mRNA levels
      increased in the kidneys, and hypoxia-inducible genes were enhanced in the
      kidney. Our findings indicated that low ambient temperature is a novel
      erythropoietic stress, which induces polycythemia by enhanced erythropoiesis.

PMID- 23155088
TI  - Lion (Panthera leo) and caracal (Caracal caracal) type IIx single muscle fibre
      force and power exceed that of trained humans.
AB  - This study investigated for the first time maximum force production, shortening
      velocity (Vmax) and power output in permeabilised single muscle fibres at 12
      degrees C from lion, Panthera leo (Linnaeus 1758), and caracal, Caracal caracal
      (Schreber 1776), and compared the values with those from human cyclists.
      Additionally, the use and validation of previously frozen tissue for contractile
      experiments is reported. Only type IIx muscle fibres were identified in the
      caracal sample, whereas type IIx and only two type I fibres were found in the
      lion sample. Only pure type I and IIa, and hybrid type IIax fibres were
      identified in the human samples - there were no pure type IIx fibres.
      Nevertheless, compared with all the human fibre types, the lion and caracal
      fibres were smaller (P<0.01) in cross-sectional area (human: 6194+/-230 MUm(2),
      lion: 3008+/-151 MUm(2), caracal: 2583+/-221 MUm(2)). On average, the felid type
      IIx fibres produced significantly greater force (191-211 kN m(-2)) and ~3 times
      more power (29.0-30.3 kN m(-2) fibre lengths s(-1)) than the human IIax fibres
      (100-150 kN m(-2), 4-11 kN m(-2) fibre lengths s(-1)). Vmax values of the lion
      type IIx fibres were also higher than those of human type IIax fibres. The
      findings suggest that the same fibre type may differ substantially between
      species and potential explanations are discussed.

PMID- 23155090
TI  - Effect of fluid viscosity on the liquid-feeding flow phenomena of a female
      mosquito.
AB  - Liquid-sucking phenomena by the two-pump system of female mosquitoes were
      investigated to understand the feeding mechanism. In most previous experimental
      studies on liquid-feeding insects, the net increase of mass was divided by the
      feeding time and fluid density to evaluate the intake rate. However, this
      weighting method is not so precise for mosquitoes, because they are too
      lightweight to measure the gain of mass accurately. In this study, the intake
      rate of female mosquitoes feeding on various sucrose solutions was estimated
      using a micro-particle image velocimetry technique. As the sucrose concentration
      increased from 1% to 50%, the intake rate decreased from 17.3 to 5.8 nl s(-1). In
      addition, the temporal volume variations of the two pump chambers were estimated
      based on the velocity and acceleration information of the flow at the center of
      the food canal of the proboscis. One pumping period was divided into four
      elementary phases, which are related to the different operational modes of the
      two pumps. According to the hypothetical model established in this study, the
      phase shift () between the two pump chambers increases from 14 to 28 ms and the
      percentage of reverse flow to forward flow in a pumping period decreases from
      7.6% to 1.7% with increasing viscosity. The developed analytical methodology thus
      aids in the study of an insect's feeding mechanism.

PMID- 23155091
TI  - Integration of alternating monocular samples during goal-directed aiming.
AB  - The current study examined the effect of interocular delay in a manual aiming
      task that required accurate end-point placement, but not precise control of a
      grip aperture. Participants aimed in binocular, monocular, or alternating
      monocular vision conditions. For the latter, 25ms monocular samples were provided
      to alternate eyes without delay (0ms), or a delay of 25 or 50ms. The interocular
      delay resulted in a longer movement time, caused by a longer time-to-peak and
      time-after-peak velocity, and a reduction in peak velocity. We suggest that the
      change in kinematics reflect a strategic response to preserve terminal aiming
      accuracy and variability when faced with an informational perturbation. These
      findings indicate that the response to the interocular delay between alternating
      monocular samples depends on the task-specific information used to control that
      behavior.

PMID- 23155092
TI  - Anchoring in rhythmic in-phase and antiphase visuomotor tracking.
AB  - Rhythmic limb movements are often anchored at particular points in the movement
      cycle. Anchoring may reveal essential task-specific information for motor
      control. We examined the effect of tracking mode (in-phase, antiphase) and gaze
      direction (left, right) on anchoring in visuomotor tracking with and without
      concurrent visual feedback of the hand movement. For in-phase tracking, anchoring
      was observed at the foveated reversal point whereas for antiphase tracking
      anchoring was observed at both reversals, suggesting the presence of two
      reference points instead of one. Anchoring at the foveated reversal reflected
      gaze anchoring (i.e., coalignment of hand and gaze) while anchoring at the
      nonfoveated reversal reflected visuomotor synchronization (i.e., the hand was
      steered to the nonfoveated reversal coincident with a target reversal at the
      point of gaze). We propose that the number and location of anchor points play a
      crucial role in the underlying control by providing reference values for error
      correction processes.

PMID- 23155094
TI  - Hepatitis B seroprevalence in persons attending youth clinics in Stockholm,
      Sweden in 2008.
AB  - Sweden is a low endemicity country for hepatitis B virus (HBV). The previously
      reported prevalence of chronic HBV is <1% and of overall markers <5%. HBV is not
      included in the universal childhood vaccination programme. Instead, selected high
      risk groups are targeted. Our aim was to examine the HBV seroprevalence in youth
      clinic clients in Stockholm and identify if this population might be a new target
      group for vaccination. In total, 515 clients aged 18-22 years were recruited.
      They completed a risk-assessment questionnaire and 464 (90%) had a serum specimen
      tested for HBV serology. Chronic HBV was found in 0.6% and 0.9% had previously
      been infected with HBV. A seroprevalence of 1.8% HBV markers was found among non
      vaccinated persons. This is lower than reported from other countries and not
      different from the general population in Sweden. However, in persons originating
      from HBV endemic countries (n = 123), the prevalence was higher, 6.5%. Only 14%
      were vaccinated and the majority hence susceptible to HBV. The target groups are
      not reached by the present vaccination strategy. Youth clinics are ideal settings
      for catch-up vaccination.

PMID- 23155093
TI  - Herpes simplex virus type 2 infection as a biomarker for sexual debut among young
      people in sub-Saharan Africa: a literature review.
AB  - Biological markers are needed in order to provide objective measures to validate
      self-reported sexual behaviour and interpret prevention trial data. In this
      review, we evaluated herpes simplex type 2 virus (HSV-2), one of the most
      prevalent sexually transmitted infections in sub-Saharan Africa as a biological
      marker of sexual debut. Based on our findings, we do not recommend using HSV-2 as
      a biomarker for sexual debut due to its low transmission probabilities and the
      fact that HSV-2 prevalence is not 100% among potential sexual partners. We
      recommend that the validation of alternative biological measures should be
      prioritized, and included in future studies and trials of interventions to reduce
      sexual health risk.

PMID- 23155095
TI  - Education provided to outgoing UK medical elective students regarding HIV risk
      and post exposure prophylaxis.
AB  - Previous studies suggested medical schools were failing to provide sufficient
      support for students undertaking electives in areas with high HIV prevalence and
      despite updated Department of Health (DoH) guidelines, not all were advising post
      exposure prophylaxis (PEP) starter packs where appropriate. This study assessed
      whether there has been improvement in risk reduction provided by home
      institutions. Questionnaires were emailed to all 29 UK medical schools offering
      an elective. A total of 26 medical schools responded. Only one failed to offer
      PEP starter packs or advice on where to obtain one. Support and advice provided
      by the other 25 varied considerably. HIV risk education and provision of PEP to
      elective students has improved. A discrepancy between advice given, supervision
      of projects and provision of PEP starter packs across UK medical schools remains.
      We reiterate recommendations put forward previously that there is a need for
      regularly updated national guidelines published by experts, issued to all medical
      schools.

PMID- 23155097
TI  - Chlamydia trachomatis, Mycoplasma genitalium and Ureaplasma urealyticum in
      clinical and non-clinical settings, Arkhangelsk Oblast, Russia.
AB  - Russia and Eastern Europe have the fastest growing HIV epidemic in the world. As
      sexually transmitted infections (STIs) play an important role in HIV
      transmission, we conducted this study to find the prevalence of three
      microorganisms associated with STIs in Arkhangelsk Oblast, Russia. First void
      urine from 1729 participants was analysed using nucleic acid amplification
      testing, and all participants completed a questionnaire. One hundred and twelve
      (6.5%) were tested positive for Chlamydia trachomatis, 67 (3.9%) for Mycoplasma
      genitalium and 221 (12.8%) for Ureaplasma urealyticum. A significant association
      was found between C. trachomatis and U. urealyticum (odds ratio [OR] 1.85; 95%
      confidence interval [CI] 1.1 to 3.0). U. urealyticum was associated with similar
      social demographics and sexual risks as C. trachomatis and M. genitalium. This
      suggests that U. urealyticum has a possible role as an STI pathogen or might be a
      contributing factor for the spread of other STIs.

PMID- 23155096
TI  - Stimulating an immune response? Oral sex is associated with less endometritis.
AB  - Secondary analysis of the PID Evaluation and Clinical Health (PEACH) data
      suggests that among women presenting with signs and symptoms of pelvic
      inflammatory disease (PID), those who reported oral sex were less likely to have
      endometritis (adjusted odds ratio [OR] 0.5 [0.3-0.8]) than those who did not
      report oral sex. Adaptive immunity requires antigenic priming of the lymphatic
      system. As lymphatic tissue is abundant in the oropharynx, oral sex could lead to
      effective immune stimulation and prevent PID. To determine whether oral sex could
      be a protective factor for PID the relationship between self-reported oral sex
      and endometritis was analysed among 619 women with clinically suspected PID who
      participated in the PEACH study. Nearly one quarter of participants reported oral
      sex in the past four weeks. These women also reported a higher number of sexual
      partners, a new partner within the past four weeks and a higher frequency of
      sexual intercourse (all P < 0.03). They were more likely to smoke (P < 0.0001),
      drink alcohol (P < 0.004) and use recreational drugs (P < 0.02). Participants
      reporting oral sex were significantly less likely to be black or to have a
      positive test for Neisseria gonorrhoeae (7.8% versus 21.6%, P = 0.001). Women who
      disclosed oral sex were significantly less likely to have endometritis after
      adjusting for race, number of partners, recent new partner, smoking, alcohol use
      and drug use (adjusted OR 0.5 [0.3-0.8]). This is the first paper showing a
      negative association between oral sex and endometritis. This may be mediated by a
      protective immune response in the genital tract following priming in the
      oropharynx. This hypothesis needs to be tested in further studies.

PMID- 23155098
TI  - Rising popularity of anal intercourse and sexual risk taking: findings from two
      national probability studies of young Croatian adults.
AB  - This study examined the prevalence and correlates of heterosexual anal
      intercourse in two national probability samples of young Croatian adults aged 18
      25 years, which were collected in 2005 and 2010. The lifetime prevalence of anal
      intercourse increased from 27% to 36%. In multivariate analysis, reporting four
      or more lifetime sexual partners was the only correlate of the experience of anal
      intercourse that was significant among both women (odds ratios [ORs] = 1.78-3.27,
      P < 0.05) and men (ORs = 3.14-4.63, P < 0.01). Information about condom use at
      most recent anal intercourse was collected in the 2010 study wave only. Age (OR =
      0.80, P < 0.05), female gender (OR = 0.29, P < 0.01), holding more negative
      attitudes towards condoms (OR = 0.28-0.32, P < 0.05) and reporting condom use at
      most recent vaginal intercourse (OR = 11.45, 95% Confidence interval [CI] = 5.68
      23.06) were associated with using a condom at most recent anal intercourse. Given
      the substantial prevalence of anal intercourse among young heterosexual adults
      and considerable sexually transmitted infection/HIV risks associated with the
      practice, sex education programmes should promote the discussion of health risks
      associated with anal eroticism.

PMID- 23155099
TI  - Association between smoking and size of anal warts in HIV-infected women.
AB  - While the association between smoking and human papillomavirus infection,
      cervical cancer, and anal cancer has been well studied, evidence on the
      association between cigarette smoking and anal warts is limited. The purpose of
      this study was to investigate if cigarette smoking status influences the size of
      anal warts over time in HIV-infected women in a sample of 976 HIV-infected women
      from the Women's Interagency HIV Study (WIHS). A linear mixed model was used to
      determine the effect of smoking on anal wart size. Even though women who were
      currently smokers had larger anal warts at baseline and slower growth rate of
      anal wart size after each visit than women who were not current smokers, there
      was no association between size of anal wart and current smoking status over
      time. Further studies on the role of smoking and interaction between smoking and
      other risk factors, however, should be explored.

PMID- 23155101
TI  - Managing HIV in pregnancy in a community-based sexual health clinic: a decade in
      review.
AB  - The management of HIV in pregnancy has evolved significantly over the past 10
      years as our experience of combination antiretroviral therapy (ART) has grown. We
      reviewed 109 pregnancies which were managed at our community-based integrated HIV
      and sexual health clinic to investigate preconception and antenatal care, and
      trends in ART over time. We document an increasing proportion of pregnancies in
      which the mother was aware of her HIV status pre-conception and conception on
      ART. Pre-conception care was sought in a minority of cases, and many women did
      not present for first antenatal review until the end of the second trimester. Of
      108 live births, there was one case of vertical transmission (0.93%). While our
      study demonstrates the efficacy of current strategies to prevent mother to child
      transmission of HIV infection, more could be done to encourage HIV-positive women
      to seek preconception advice and to attend for early review in the first
      trimester.

PMID- 23155100
TI  - Evaluating the implementation of nurse-initiated HIV rapid testing in three
      Veterans Health Administration substance use disorder clinics.
AB  - Individuals with substance use disorders (SUDs) are at higher risk of HIV
      infection, yet recent studies show rates of HIV testing are low among this
      population. We implemented and evaluated a nurse-initiated HIV oral rapid testing
      (NRT) strategy at three Veterans Health Administration SUD clinics.
      Implementation of NRT includes streamlined nurse training and a computerized
      clinical reminder. The evaluation employed qualitative interviews with staff and
      a quantitative evaluation of HIV testing rates. Barriers to testing included lack
      of laboratory support and SUD nursing resistance to performing medical
      procedures. Facilitators included the ease of NRT integration into workflow,
      engaged management and an existing culture of disease prevention. Six-months post
      intervention, rapid testing rates at SUD clinics in sites 1, 2, and 3 were 5.0%,
      1.1% and 24.0%, respectively. Findings indicate that NRT can be successfully
      incorporated into some types of SUD subclinics with minimal perceived impact on
      workflow and time.

PMID- 23155102
TI  - Association between herpes simplex virus type 2 and HIV-1 in a population of
      married couples from Dakar, Senegal.
AB  - Numerous studies suggest that herpes simplex virus type 2 (HSV-2) increases the
      risk of HIV-1 infection but recent clinical trials of HSV-2 suppressive therapy
      failed to show an effect. We assessed the putative association between HSV-2 and
      HIV-1 in a population of HIV-concordant-negative, HIV-1-discordant and HIV-1
      concordant-positive married couples from Dakar, Senegal. In agreement with
      previous studies, we observed a strong overall association between HSV-2 and HIV
      1 (odds ratio 4.61; P < 0.001). However, this association was mainly determined
      by a low HSV-2 prevalence in HIV-concordant-negative couples compared with HIV-1
      discordant and HIV-1-concordant-positive couples (23% versus 59% and 66%,
      respectively; P < 0.001). We observed no further differences in HSV-2 prevalence
      between HIV-1-discordant and HIV-1-concordant-positive couples (59% and 66%,
      respectively; P = 0.483). Neither the index (59% versus 62%, P = 1.000) nor
      recipient partners (41% versus 63%, P = 0.131) in HIV-1-discordant and HIV-1
      concordant-positive couples showed significant differences in HSV-2 prevalence.
      HSV-2 does not constitute a clear risk factor for HIV-1 infection in this
      population.

PMID- 23155103
TI  - HIV testing and counselling in Colombia: evidence from a national health survey
      and recommendations for health-care services.
AB  - The purpose of this study was to assess the prevalence of, and the factors
      associated with HIV testing and pre- and post-test counselling (PPTC) in
      Colombia. Cross-sectional data from the National Health Survey carried out during
      2007 were analysed. Data were gathered from records of 29,760 individuals between
      the ages of 18 and 69 from the main regions of the country. Only 19.7% of the
      sample had taken an HIV test. Men, people with no education, those not affiliated
      with the health-care system, residents of rural areas and those aged older than
      65 were less likely to have been tested for HIV; 42% of those tested did not
      receive pre-test counselling and 56.9% received no report of the results.
      Considering the low prevalence of HIV testing among the Colombian population, it
      is necessary to design and apply guidelines for HIV screening in all health-care
      settings and to conduct targeted testing in high-risk sub-populations. A national
      norm of PPTC in those who undergo HIV testing should be examined.

PMID- 23155104
TI  - Most adolescents who participate in school-based screenings for sexually
      transmitted infections do not perceive themselves at high risk of sexually
      transmitted infection.
AB  - Statements of study limitations have been made in a number of reports that
      voluntary participants in school-based screenings for sexually transmitted
      infections (STIs) may be individuals who self-select for participation because
      they perceive themselves at high risk of STI. We surveyed 3336 students
      participating in the New Orleans school-based screening for chlamydia and
      gonorrhoea to determine their perceived personal risk of STI. Among all screening
      participants, 1183 (35.5%) estimated that their chances of getting an STI were
      pretty high or very high and 2153 (64.5%) estimated that their chances were none,
      not very high or medium. These findings indicate that most participants in the
      New Orleans school-based screening for chlamydia and gonorrhoea do not perceive
      themselves at high risk of STI.

PMID- 23155105
TI  - An audit of partner notification for syphilis and HIV.
AB  - Partner notification (PN) is a vital tool used by genitourinary (GU) medicine
      services in the public health control of sexually transmitted infections. We
      audited our PN outcomes for syphilis and HIV, over an 18-month period, at the
      Edinburgh GUM clinic. Follow-up information on testing was only available for 58%
      of traceable syphilis contacts and 59% of traceable HIV contacts, though
      substantially larger percentages in each case, respectively 78% and 90%, were
      informed regarding their risk of exposure. Furthermore, the department achieved
      screening verification in 78% of identifiable syphilis contacts and 94% of
      identifiable HIV partners.

PMID- 23155106
TI  - Unmasking of progressive multifocal leukoencephalopathy in a patient with HIV-2.
AB  - HIV-2 is common in West Africa but rarely found in developed countries. It
      usually has a milder disease course than HIV-1 and clinical presentations of
      neurological syndromes in HIV-2 are extremely rare. We report a case of a HIV-2
      infected, 46-year-old woman originally from Cote d'Ivoire who presented with
      possible intracerebral toxoplasmosis infection then developed progressive
      multifocal leukoencephalopathy.

PMID- 23155107
TI  - Idiopathic ileocolitis with perforation associated with HIV infection:
      thalidomide treatment.
AB  - Idiopathic cutaneous ulcers, oesophageal ulcers and severe ulcerative ileocolitis
      occurred in a human immunodeficiency virus (HIV)-infected patient early after the
      initiation of combination antiretroviral therapy. This massive inflammatory
      process led to acute colonic perforation on two occasions. The disease was
      refractory to standard therapy, but responded successfully to thalidomide. Here,
      we discuss the potential benefits of thalidomide in refractory inflammatory
      processes in HIV-infected patients.

PMID- 23155108
TI  - Visiting friends and relatives may be a risk for non-adherence for HIV-positive
      travellers.
AB  - We report three cases of immigrants to Australia, living with HIV/AIDS, who,
      while travelling in countries of origin or migration, were unable to continue to
      take their antiretrovirals appropriately. We discuss the possible reasons for
      this and ways to reduce the possibility of it happening. Travel may be a
      significant risk factor for non-adherence; pre-travel advice and planning might
      help to prevent it occurring.

PMID- 23155109
TI  - Genital elephantiasis due to donovanosis: forgotten but not gone yet ...
AB  - Genital elephantiasis is a disease that is characterized by massive enlargement
      of the genitalia. Early aetiological diagnosis is of paramount importance so that
      development of genital elephantiasis can be prevented; otherwise it is not
      completely reversible with medical therapy and often requires surgical
      intervention. Chronic mental distress and disability can result as it interferes
      with daily/routine activities of the affected individual. Over time, the
      infectious causes of genital elephantiasis have evolved, from syphilis in the pre
      penicillin era to donovanosis, lymphogranuloma venereum and recently filariasis,
      tuberculosis, leishmaniasis, HIV and chromoblastomycosis. With a declining
      prevalence globally, donovanosis is at risk of being forgotten as a cause of
      genital swelling; however, it is known to persist for years without treatment and
      can lead to complications such as lymphoedema and genital mutilation. We herein
      present a case of genital elephantiasis that was eventually diagnosed as being
      due to donovanosis.

PMID- 23155110
TI  - Resection of PCNSL, if safely possible, seems to be better than biopsy:
      challenging a paradigm?

PMID- 23155112
TI  - Ultrathin specimen preparation by a low-energy Ar-ion milling method.
AB  - The low-energy Ar-ion milling method was used to prepare ultrathin specimens for
      transmission electron microscope observation. The samples were thinned initially
      by a usual focused ion beam technique or typical Ar-ion milling with a high
      energy of 2-10 keV and were thinned additionally by an Ar-ion beam with an energy
      less than 1 keV, typically 500-900 eV. This low-energy ion beam was scanned over
      the specimen, and secondary electrons induced by the ion beam could be detected
      to form secondary electron images with a resolution of a few micrometre. Because
      a desired area can be selected and thinned by the low-energy ion beam,
      redeposition or cross contamination from irradiation of a metal grid that
      supports the sample can be prevented. It was shown that the low-energy Ar-ion
      beam thins a surface amorphous damage layer preferentially and effectively rather
      than a crystal specimen. Images from ultrathin specimens of two different
      materials revealed a detailed structure.

PMID- 23155113
TI  - A new F-actin structure in fungi: actin ring formation around the cell nucleus of
      Cryptococcus neoformans.
AB  - The F-actin cytoskeleton of Cryptococcus neoformans is known to comprise actin
      cables, cortical patches and cytokinetic ring. Here, we describe a new F-actin
      structure in fungi, a perinuclear F-actin collar ring around the cell nucleus, by
      fluorescent microscopic imaging of rhodamine phalloidin-stained F-actin.
      Perinuclear F-actin rings form in Cryptococcus neoformans treated with the
      microtubule inhibitor Nocodazole or with the drug solvent dimethyl sulfoxide
      (DMSO) or grown in yeast extract peptone dextrose (YEPD) medium, but they are
      absent in cells treated with Latrunculin A. Perinuclear F-actin rings may
      function as 'funicular cabin' for the cell nucleus, and actin cables as
      intracellular 'funicular' suspending nucleus in the central position in the cell
      and moving nucleus along the polarity axis along actin cables.

PMID- 23155114
TI  - A pilot study of the effectiveness of home teleconsultations in paediatric
      palliative care.
AB  - We conducted a pilot study to investigate the effectiveness of a home telehealth
      service for paediatric palliative care consultations. Over a 10 week period, 14
      of the 17 caregivers approached to be part of the study agreed to participate.
      Families were allocated, non-randomly, to a control group (usual care) or an
      intervention group (usual care with the addition of home telehealth
      consultations). The primary outcome measure was quality-of-life score. Caregivers
      were surveyed for up to 99 days following recruitment. A descriptive analysis of
      the quality-of-life data showed no differences between caregivers in the two
      groups. However, important lessons were learnt regarding factors which influence
      the success of studies in this population group, and the domains of caregiver
      quality-of-life that warrant intervention. Palliative care is complex, and
      multiple interventions and supports are required if care is to be managed at
      home. Home telehealth consultations are a feasible and acceptable means of
      facilitating a palliative care consultation which can reduce the burden on
      families at a distressing time.

PMID- 23155115
TI  - Tremor irregularity, torque steadiness and rate of force development in
      Parkinson's disease.
AB  - We investigated lower-extremity isometric tremor Approximate Entropy
      (irregularity), torque steadiness and rate of force development (RFD) and their
      associations to muscle activation strategy during isometric knee extensions in
      patients with Parkinson's disease (PD). Thirteen male patients with idiopathic PD
      and 15 neurologically healthy matched controls performed isometric maximal
      contractions (extension/flexion) as well as steady submaximal and powerful
      isometric knee extensions. The patients with PD showed decreased isometric tremor
      irregularity. Torque steadiness was reduced in PD and the patients had increased
      muscle coactivation. A markedly lower RFD was found in PD and the decreased RFD
      correlated with reduced agonist muscle activation. Furthermore, patient RFD
      correlated with the Movement-Disorder-Society-Unified-Parkinson's-Disease-Rating
      Scale 3 (motor part) scores. We concluded that both knee isometric tremor
      Approximate Entropy and torque steadiness clearly differentiate between patients
      with PD and healthy controls. Furthermore, severely compromised RFD was found in
      patients with PD and was associated with decreased agonist muscle activation.

PMID- 23155116
TI  - Caution during use of desmopressin in IPSS.

PMID- 23155117
TI  - Hypohydration does not alter standing balance.
AB  - We examined the effect of body water deficits on standing balance and sought to
      determine if plasma hyperosmolality (P(osm)) and/or volume reduction
      (%DeltaV(plasma)) exerted independent effects. Nine healthy volunteers completed
      three experimental trials which consisted of a euhydration (EUH) balance test, a
      water deficit session and a hypohydration (HYP) balance test. Hypohydration was
      achieved both by exercise-heat stress to 3% and 5% body mass loss (BML), and by a
      diuretic to 3% BML. Standing balance was assessed during quiet standing on a
      force platform with eyes open and closed. With eyes closed, hypohydration
      significantly decreased medial-lateral sway path and velocity by 13% (both p <
      .040). However, 95% confidence intervals for the mean difference between EUH and
      HYP were all within the coefficient of variation of EUH measures, indicating
      limited practical importance. Neither V(plasma) loss nor P(osm) increases were
      associated with changes in balance. We concluded that standing balance was not
      altered by hypohydration.

PMID- 23155118
TI  - An alternative procedure for extraction of DNA from ancient and weathered bone
      fragments.
AB  - Bone is the most challenging tissue for DNA extraction and purification.
      Expensive commercial kits and specific equipments are often used in forensic and
      anthropology laboratories towards that goal. We present here an integrated
      procedure that gives satisfactory results for DNA preparation from fresh, ancient
      or weathered bones. Extraction is performed under simple but efficient vacuum
      controlled conditions that greatly limit the risks of cross-contaminations. The
      whole process has been designed to minimize the need for expensive equipment and
      chemicals, and to be compatible with any molecular biology laboratory. In
      addition, no toxic reagents are necessary and the procedure is straightforward.
      Combined with quantitative polymerase chain reaction (qPCR), this method allows
      species identification and sex determination from subcellular amount of DNA (1-5
      pg). In addition, enough DNA is generally obtained for human DNA profiling if
      necessary. The whole procedure from bone treatment to the final qPCR results
      takes less than 48 hours. This procedure should allow any laboratory with
      standard molecular biology equipment and expertise to perform bone DNA
      characterization whenever necessary. 

PMID- 23155119
TI  - Decomposed and non-decomposed bodies retrieved from water: a comparative
      approach.
AB  - The cause and manner of death in submersion cases are a routine challenge for
      forensic pathologists as they present considerable diagnostic difficulties. The
      present study was undertaken with a view to determine the characteristic pattern
      in bodies retrieved from water. From a total of 6779 medicolegal deaths reported
      at an Apex Medical Centre, Yeotmal, a rural district of Maharashtra over a 10
      year study period, only 110 cases (1.6%) were decomposed and 243 cases (3.6%)
      were non-decomposed bodies retrieved from water with a rate of 0.6 decomposed
      body as compared with 1.4 non-decomposed bodies per 100,000 population per year.
      However, out of total 353 bodies retrieved from water, 31.2% were decomposed and
      68.8% non-decomposed. Male predominance was seen in both groups with peak at 31
      40 years. The cause and manner of death were ascertained as 89.9% and 82.7%,
      respectively, in decomposed bodies as compared with 100% and 96.3%, respectively,
      in non-decomposed bodies. Drowning was the commonest cause of death in both
      groups with suicide as the commonest manner of death in decomposed bodies in
      contrast to accidental in non-decomposed bodies. Excessive amount of pleural
      fluid, aquatic animal activity and mud/vegetation in lower respiratory tract was
      more commonly encountered in decomposed bodies. However, fine white froth was not
      seen in any of the cases in contrast to 81% non-decomposed bodies. Bodies were
      commonly recovered from wells in both groups. Most of the bodies were retrieved
      in the rainy season followed by summer and winter seasons in both groups.

PMID- 23155121
TI  - Brachytherapy using injectable seeds that are self-assembled from genetically
      encoded polypeptides in situ.
AB  - Brachytherapy is a common clinical technique involving implantation of sealed
      radioactive "seeds" within a tumor to selectively irradiate the tumor mass while
      minimizing systemic toxicity. To mitigate the disadvantages associated with
      complex surgical implantation and subsequent device removal procedures, we have
      developed an alternative approach using a genetically encoded peptide polymer
      solution composed of a thermally responsive elastin-like polypeptide (ELP)
      radiolabeled with (131)I that self-assembles into radionuclide seeds upon
      intratumoral injection. The formation of these nontoxic and biodegradable polymer
      seeds led to prolonged intratumoral retention (~85% ID/tumor 7 days
      postinjection) of the radionuclide, elicited a tumor growth delay in 100% of the
      tumors in two human xenografts (FaDu and PC-3), and cured more than 67% of tumor
      bearing animals after a single administration of labeled ELP. These results
      suggest that in situ self-assembly of biodegradable and injectable radionuclide
      containing polypeptide seeds could be a promising therapeutic alternative to
      conventional brachytherapy.

PMID- 23155122
TI  - Menstrual phase and depressive symptoms differences in physiological response to
      nicotine following acute smoking abstinence.
AB  - INTRODUCTION: Accumulating evidence has linked depressive symptoms and sex
      hormones to risk for relapse; however, the specific mechanisms involved in these
      associations remain unknown. This randomized crossover study assessed
      physiological response to nicotine by menstrual phase in female smokers with and
      without depressive symptoms following acute smoking abstinence. METHODS: Females,
      ages 18-40 years with regular menstrual cycles, not on exogenous hormones or
      psychotropic medications, who reported smoking >= 5 cigarettes/day were enrolled.
      Participants were stratified into 2 groups: no depressive symptoms (NDS; n = 23)
      and depressive symptoms (DS; n = 24). After 4 days of biochemically verified
      smoking abstinence, participants completed 2 laboratory sessions in the
      follicular (F) and luteal (L) phases. Participants used nicotine nasal spray at
      Time 0, and blood pressure, heart rate, and serum nicotine were measured at Time 
      1, 5, 10, 20, 30, 45, 60, and 90 min. RESULTS: Participants (n = 47) were 29.1 +/
      6.8 years old and smoked an average of 12.5 +/- 5.1 cigarettes/day. The NDS
      group had more pronounced menstrual phase differences (F > L) in diastolic blood
      pressure, heart rate, and maximum concentrations of nicotine compared with the DS
      group (p < .05). CONCLUSIONS: This study observed an interaction between sex
      hormones and depressive symptoms such that those without depressive symptoms had
      a greater menstrual phase difference in the physiological response to nicotine.
      These data offer additional support for the role of sex hormones in the
      physiological response to nicotine, which may play a role in menstrual phase
      effects on smoking cessation.

PMID- 23155123
TI  - An adenovirus-based vaccine with a double-stranded RNA adjuvant protects mice and
      ferrets against H5N1 avian influenza in oral delivery models.
AB  - An oral gene-based avian influenza vaccine would allow rapid development and
      simplified distribution, but efficacy has previously been difficult to achieve by
      the oral route. This study assessed protection against avian influenza virus
      challenge using a chimeric adenovirus vector expressing hemagglutinin and a
      double-stranded RNA adjuvant. Immunized ferrets and mice were protected upon
      lethal challenge. Further, ferrets immunized by the peroral route induced cross
      clade neutralizing antibodies, and the antibodies were selective against
      hemagglutinin, not the vector. Similarly, experiments in mice demonstrated
      selective immune responses against HA with peroral delivery and the ability to
      circumvent preexisting vector immunity.

PMID- 23155124
TI  - Clinical specificity of the enzyme immunoassay test for coccidioidomycosis varies
      according to the reason for its performance.
AB  - The diagnosis of coccidioidomycosis relies heavily on serologic test results in
      addition to clinical history, physical examination, and radiographic findings.
      Use of the enzyme immunoassay (EIA) has increased because it is rapidly performed
      and does not require referral to a reference laboratory, as do complement
      fixation and immunodiffusion tests. However, interpretation of immunoglobulin M
      (IgM) reactivity by EIA in the absence of immunoglobulin G (IgG) reactivity has
      been problematic. We conducted a retrospective medical record review of all
      patients with such IgM reactivity at our institution to identify situations where
      the finding was more likely to be clinically specific for coccidioidal infection.
      From 1 January 2004 through 31 December 2008, a total of 1,117 patients had
      positive EIA coccidioidal serology or EIA IgM-only reactivity; of these, 102
      patients (9%) had EIA IgM-only reactivity. Among the 102 patients with EIA IgM
      only reactivity, 60 were tested to evaluate symptomatic illness, 13 for follow-up
      of previously abnormal serology, and 29 for screening purposes. Of the 102
      patients, 80 (78%) had positive serologic findings by other methods or had
      positive culture or histology. Fifty-four (90%) of the 60 patients whose serology
      was performed to evaluate symptomatic illness had coccidioidal infection, whereas
      13 (45%) of 29 patients whose serology was performed for screening purposes had
      coccidioidal infection. Of the 102 patients with isolated IgM reactivity by EIA,
      12 later seroconverted to IgG and IgM reactivity. The use of EIA for screening in
      29 asymptomatic persons was associated with unconfirmable results in 13 (45%).
      Although the majority of patients in our study with isolated IgM reactivity by
      EIA had probable or confirmed coccidioidomycosis, this result must be interpreted
      with caution for asymptomatic patients.

PMID- 23155125
TI  - Cannabis misinterpretation and misadventure in a coroner's court.
AB  - A 37-year-old, one-pack-per-day tobacco smoker collapsed and died at home. At
      autopsy, he had an occluded left anterior descending coronary artery. Delta(9)
      Tetrahydrocannabinol-carboxylic acid was found in his urine but no cannabinoids
      were detected in his blood. Misadventure was the inquest verdict on the basis of
      the urinary cannabis, with acute myocardial infarction as the primary cause and
      cannabis as the secondary cause of death. Such a conclusion is a
      misinterpretation of the evidence when the time duration for cannabis as a
      trigger for myocardial infarction is at most two hours. The absence of cannabis
      in the blood likely places the time since inhalation at more than two hours. The
      role of tobacco smoking as a trigger was ignored. Cotinine, the biochemical
      marker of tobacco smoke, should be added to the standard toxicological screen in
      the guidelines on autopsy practice of the Royal College of Pathologists.

PMID- 23155126
TI  - Platelet-rich plasma and blood components for non-transfusion use: technical and
      medicolegal aspects.
AB  - There are a large number of publications describing the use of platelet-rich
      plasma (PRP) in multiple fields of application. These illustrate a large number
      of therapeutic elements with different and specific actions within 'platelet gel'
      (this term is used in the current regulations to define this product). This term,
      however, lacks specificity and, depending on the method used in its production is
      variable both in its blood composition and in platelet concentration, and several
      publications consider better and easier methods of platelet gel production, which
      may or may not lead to greater standardization in the product. The authors
      illustrate the general aspects of PRP and other blood components for non
      transfusion use, briefly touching on the history and different fields of
      application and the rational of for its use. Given the increased use of such
      preparations, the authors describe critically the regulations in force in Europe
      and propose a new regulatory framework aimed to simplify and facilitate the use
      of such material as a therapeutic agent within medicine.

PMID- 23155129
TI  - How frequent is complete recovery after suicidal hanging?

PMID- 23155130
TI  - The impact of direction of great saphenous vein total stripping on saphenous
      nerve injury.
AB  - OBJECTIVES: To examine and compare the effects of downwards versus upwards total
      stripping of great saphenous vein (GSV) on saphenous nerve (SN) injury using
      clinical and electrophysiological studies. METHODS: Fifty patients with
      varicosities were equally and randomly assigned to undergo total, upwards
      stripping (group A) or downwards stripping (group B) of GSV during saphenectomy.
      SN function was measured with electroneurogram (ENG) before operation, two weeks
      and 12 weeks after, in order to record the incidence and type of SN injury.
      Clinical signs of SN injury were also recorded at the same time points. The
      results were statistically analysed. RESULTS: There were no statistical
      significant differences on the occurrence of SN injury between groups A and B at
      two and 12 weeks, respectively, as confirmed with ENG studies and clinical
      evaluation. There were no differences between the two techniques with regard to
      the type of SN injury. SN injury was significantly ameliorated from 34% to 6%
      during the first three months. CONCLUSION: SN injury was equally observed after
      downwards or upwards total stripping of the GSV, as confirmed by ENG and clinical
      evaluation, with no differences in injury type. SN injury tends to be relieved
      through time in most patients.

PMID- 23155131
TI  - Percutaneous transluminal angioplasty in a patient with chronic cerebrospinal
      venous insufficiency and persistent left superior vena cava.
AB  - Chronic cerebrospinal venous insufficiency (CCSVI) is a syndrome characterized by
      stenoses of the internal jugular veins (IJVs) and/or azygos veins and formation
      of collateral venous channels. A case of a 57-year-old patient with CCSVI in whom
      the venous outflow from the left IJV to the right atrium occurred through a
      venous anomaly, the persistent left superior vena cava (PLSVC), is reported.
      PLSVC is caused by persistence of the left anterior cardinal vein that drains
      blood from the limb effluent from the left and the left side of head and neck
      into coronary sinus (Type a), or in the left atrium (Type b). PLSVC can be
      associated either with innominate vein hypoplasia or other congenital heart
      abnormalities. Because of evidence of left innominate vein hypoplasia,
      angioplasty was not performed using the ordinary route but passing with the
      balloon directly through the PLSVC up to the left IJV. Finally, angioplasty was
      carried out in a standard manner in the right IJV as well as in the azygous vein.
      Confirmation angiogram revealed complete reopening of all treated vessels with no
      evidence of peri- and postoperative complications. The patient was discharged
      home the following day in good general conditions. PLSVC is a rare congenital
      vein anomaly but in case of concomitant innominate vein hypoplasia may prove to
      be a valuable alternative to treat patients with IJV diseases. 

PMID- 23155132
TI  - Assessment of jugular endovascular malformations in chronic cerebrospinal venous
      insufficiency: colour-Doppler scanning and catheter venography compared with
      intravascular ultrasound.
AB  - OBJECTIVES: Chronic cerebrospinal venous insufficiency (CCSVI) is a malformative
      condition characterized by several anomalies of the azygos and/or internal
      jugular veins (IJVs). Recommended diagnosis of CCSVI is performed with colour
      Doppler (CD) sonography. Though catheter venography (CV) is considered as the
      gold standard for determining vascular anatomy, its uniplanar point of view does
      not allow an overall evaluation of endoluminal structures. This limit could be
      addressed by intravascular ultrasound (IVUS). The aim of this report is to
      evaluate, in patients with multiple sclerosis (MS), the accuracy of CD sonography
      and CV versus IVUS in estimating the diameter and the cross-sectional area (CSA)
      of the IJVs and in detecting jugular endoluminal malformations (JEM). METHOD:
      Forty-five MS patients with CCSVI, diagnosed by CD sonography, were submitted to
      CV during IJVs angioplasty. Twenty-five subjects were also examined with IVUS.
      The IJVs maximum diameter (MAXD) and CSA were estimated. CD and CV data were
      compared with IVUS data with the Bland-Altman method. RESULTS: The mean
      difference in IJV MAXD recorded by CD and IVUS was -0.5 mm. The mean difference
      in IJV MAXD recorded by CV and IVUS was 3.36 mm. The mean difference in IJV CSA
      recorded by CD and IVUS was -11.2 mm(2). JEM recorded by IVUS were detected by CD
      sonography and CV with 88% and 32% accuracy, respectively. CONCLUSIONS: CV was
      significantly inferior to CD sonography and IVUS in detecting JEM. Differences
      between IVUS and CD sonography in detecting JEM and in quantifying jugular
      diameters were not significant. The IJV CSA was underestimated by CD sonography
      compared with IVUS. CD sonography was proven to be important in the anatomical
      characterization of CCSVI, providing useful information for correct intravascular
      treatment.

PMID- 23155133
TI  - Variability of interface pressure produced by ready-to-wear compression
      stockings.
AB  - PURPOSE: To assess the variability of interface pressure and changes in this
      pressure over one month time interval under ready-to-use compression stockings.
      METHODS: Fifteen healthy volunteers with a broad range of sizes and shapes of the
      calves were included in final analysis. Each volunteer sequentially used six
      pairs of stockings daily for one month each. The six pair set consisted of
      stockings of three compression classes (class 1: 20-30 mmHg, class 2: 30-40 mmHg
      and class 3: 40-50 mmHg), made of two materials with different stiffnesses.
      Interface pressure measurements were performed at B1 point using SIGaT((r))
      tester (Ganzoni-Sigvaris, St Gallen, Switzerland). Interface pressure was
      measured in supine and standing positions, and during performing 10 tiptoes.
      Pressure measurements were performed twice (in the morning and after using
      stockings for eight hours) on the first day of using each pair of stockings, and
      repeated on the 30th day. RESULTS: At the time of the first use the interface
      pressure was within the range specified by the manufacturer for 160 out of 180
      individual stockings. Twenty stockings (11.1%) produced interface pressure which
      was 5 mmHg or more outside the range of specified compression class. In 16 of
      these cases it was only one of the pair of stockings from the same box that
      produced lower than specified pressure. The pressure under stockings did not
      change significantly during the day. After one month the interface pressure under
      the class 1 stockings decreased on average by 1.4 +/- 4.3 mmHg (P = 0.013). Class
      2 and 3 stockings showed minimal pressure changes which were not statistically
      significant. CONCLUSIONS: In vivo measurements of interface pressure should be a
      requirement for clinical studies of compression stockings, and may be reasonable
      for ensuring appropriate pressure level in clinical practice.

PMID- 23155134
TI  - Endovenous laser ablation of varicose perforating veins with the 1470-nm diode
      laser using the radial fibre slim.
AB  - BACKGROUND: Endovenous Laser Ablation (EVLA) is one of the most accepted
      treatment options for varicose veins. The aim of this study was to investigate
      the efficacy and safety of the new radial fiber slim (ELVeS-radial-slim kitTM)
      for the 1470 nm diode laser in perforator veins with a 1 month follow-up.
      METHODS: Our prospective observational cohort study comprised 69 perforating
      veins in 55 patients. Ninety percent of all patients were in the CEAP-stage C3
      C6. The radial fiber slim was used to occlude the perforating vein and the great
      or small saphenous vein in the same procedure. The primary efficacy endpoint of
      the study was ultrasonographically proven elimination of venous reflux in the
      perforating vein after at least one month. Secondary efficacy and further safety
      end points after one month were as follows: (1) sonographic exclusion of
      recanalization of the treated vein segments, (2) deep vein thrombosis (DVT),
      clinical pulmonary embolism (PE), or superficial vein thrombosis (SVT) as defined
      by objective testing, (3) death from any cause, (4) persistent clinical
      complaints such as pain and paresthesia. RESULTS: Follow-up could be completed in
      all patients. In all treated perforating varicose veins, occlusion with
      elimination of reflux could be demonstrated immediately after the procedure.
      After one month 95.6% of the treated veins were still occluded (67/69). During
      follow-up, we did not diagnose any DVT, PE or SVT in the area related to the
      treated perforating vein. No patient died. One patient reported paresthesia
      distally of the puncture site. CONCLUSION: Endovenous laser treatment of varicose
      perforating veins with 1470 nm diode laser using the radial fiber slim is
      effective and safe with low recanalization rates during 1-month follow-up.

PMID- 23155135
TI  - Breast MRI use uncommon among U.S. women.
AB  - BACKGROUND: The goal of breast cancer screening is to reduce breast cancer
      mortality. Mammography is the standard screening method for detecting breast
      cancer early. Breast MRI is recommended to be used in conjunction with
      mammography for screening subsets of women at high risk for breast cancer. We
      offer the first study to provide national estimates of breast MRI use among women
      in the United States. METHODS: We analyzed data from women who responded to
      questions about having a breast MRI on the 2010 National Health Interview Survey.
      We assessed report of having a breast MRI and reasons for it by sociodemographic
      characteristics and access to health care and computed five-year and lifetime
      breast cancer risk using the Gail model. RESULTS: Among 11,222 women who
      responded, almost 5% reported ever having a breast MRI and 2% reported having an
      MRI within the 2 years preceding the survey. Less than half of the women who
      reported having a breast MRI were at increased risk. Approximately 60% of women
      reported having the breast MRI for diagnostic reasons. Women who ever had a
      breast MRI were more likely to be older, Black, and insured and to report a usual
      source of health care as compared with women who reported no MRI. CONCLUSIONS:
      Breast MRI use may be underused or overused in certain subgroups of women.
      IMPACT: As access to health care improves, the use of breast MRI and the
      appropriateness of its use for breast cancer detection will be important to
      monitor.

PMID- 23155136
TI  - A comparison of human papillomavirus genotype-specific DNA and E6/E7 mRNA
      detection to identify anal precancer among HIV-infected men who have sex with
      men.
AB  - BACKGROUND: Human papillomavirus (HPV) RNA detection is reportedly more specific
      for the detection of anogenital precancer than HPV DNA but it is unknown whether
      this is due to detection of RNA or due to HPV genotype restriction. METHODS: A
      total of 363 human immunodeficiency virus (HIV)-positive men who have sex with
      men had two anal cytology samples taken and were evaluated using high-resolution
      anoscopy and biopsies of visible lesions. Anal specimens were tested for E6/E7
      RNA for five carcinogenic HPV genotypes (HPV16, 18, 31, 33, and 45) and tested
      for the DNA of 13 carcinogenic HPV genotypes. RESULTS: DNA testing was more
      likely to be positive than RNA testing (53% vs. 48%; P = 0.02) for the same five
      HPV genotypes in aggregate. When restricted to five HPV genotypes targeted by the
      RNA test, the sensitivity to detect anal precancer was the same for DNA and RNA
      (81%), whereas RNA was more specific than DNA (65% vs. 58%; P = 0.007). In
      comparison, DNA detection of all 13 carcinogenic HPV genotypes was more sensitive
      (96% vs. 81%; P = 0.001) but much less specific (65% vs. 33%; P < 0.001) as
      compared with RNA detection of the five HPV genotypes. CONCLUSION: After
      controlling for HPV genotypes, RNA was only slightly more specific than DNA
      detection for anal precancer. IMPACT: DNA or RNA testing for a subset of the most
      carcinogenic HPV genotypes may be useful for distinguishing between those HPV
      positive men at higher and lower risk of anal precancer and cancer.

PMID- 23155137
TI  - Prospective study of HPV16 viral load and risk of in situ and invasive squamous
      cervical cancer.
AB  - BACKGROUND: A strong association has been shown between high viral DNA load (VL)
      of human papillomavirus (HPV) type 16 and risk for cervical cancer in situ (CIS).
      However, little data is available for the significance of VL in invasive squamous
      cell carcinoma (SCC). METHODS: In 2 nested case-control studies among women
      participating in cervical screening, with a cytologically normal first smear, we
      collected 5,665 smears from 621 women with CIS, 457 with SCC, and individually
      matched controls. All smears were tested for HPV, and VLs of HPV16 positive
      smears were quantified using real time-PCR. The median follow-up until diagnosis
      of CIS or SCC was 6.1 to 7.7 years. RESULTS: Low VL's were common among both CIS
      and SCC case women, until 1 to 2 years before diagnosis when a surge in VL
      occurred. The relative risk (RR) associated with low viral load of HPV16 was
      around 10 for CIS, and 10 to 20 for SCC throughout 10 years before diagnosis,
      compared with HPV16-negative women. For women with medium to high VL, the risk
      for CIS was greatly increased from 5 years before diagnosis [RR, 19; 95%
      confidence interval (CI), 7-48]. In SCC, a high VL conferred an increased risk,
      but only from 3 years before diagnosis [RR, 60; 95% CI, 6-580]. CONCLUSIONS: We
      show differing risk functions associated with HPV16 viral load in CIS and SCC,
      respectively. We further show that viral loads were unexpectedly low early in the
      SCC disease process. IMPACT: HPV16 viral load appears highly complex which may
      limit its use in cervical screening.

PMID- 23155138
TI  - KRAS testing and epidermal growth factor receptor inhibitor treatment for
      colorectal cancer in community settings.
AB  - BACKGROUND: In metastatic colorectal cancer (mCRC), mutations in the KRAS gene
      predict poor response to EGF receptor (EGFR) inhibitors. Clinical treatment
      guidelines now recommend KRAS testing if EGFR inhibitors are considered. Our
      study investigates the clinical uptake and utilization of KRAS testing. METHODS:
      We included 1,188 patients with mCRCs diagnosed from 2004 to 2009, from seven
      integrated health care delivery systems with a combined membership of 5.5
      million. We used electronic medical records and targeted manual chart review to
      capture the complexity and breadth of real-world clinical oncology care. RESULTS:
      Overall, 428 patients (36%) received KRAS testing during their clinical care, and
      266 (22%) were treated with EGFR inhibitors. Age at diagnosis (P = 0.0034),
      comorbid conditions (P = 0.0316), and survival time from diagnosis (P < 0.0001)
      influence KRAS testing and EGFR inhibitor prescribing. The proportion who
      received KRAS testing increased from 7% to 97% for those treated in 2006 and
      2010, respectively, and 83% of all treated patients had a KRAS wild-type
      genotype. Most patients with a KRAS mutation (86%) were not treated with EGFR
      inhibitors. The interval between mCRC diagnosis and receipt of KRAS testing
      decreased from 26 months (2006) to 10 months (2009). CONCLUSIONS: These findings
      show rapid uptake and incorporation of this predictive biomarker into clinical
      oncology care. IMPACT: In this delivery setting, KRAS testing is widely used to
      guide treatment decisions with EGFR inhibitors in patients with mCRCs. An
      important future research goal is to evaluate utilization of KRAS testing in
      other delivery settings in the United States.

PMID- 23155139
TI  - Alcohol and acetaldehyde in African fermented milk mursik--a possible etiologic
      factor for high incidence of esophageal cancer in western Kenya.
AB  - BACKGROUND: Esophageal cancer is unusually frequent in Western Kenya, despite the
      low prevalence of classical risk factors such as heavy drinking and tobacco
      smoking. Among Kenyans consumption of fermented milk is an old tradition. Our
      hypothesis is that alcohol and acetaldehyde are produced during the fermentation
      process and that their carcinogenic potential contributes to the high incidence
      of esophageal cancer. METHODS: Eight samples of mursik milk starter cultures were
      collected from different Kalenjin families in the Rift Valley province, Western
      Kenya. A protocol provided by the families was used for milk fermentation.
      Ethanol and acetaldehyde levels were measured by gas chromatography. The
      microbial flora in starter cultures was identified by 16S and 18S sequencing.
      RESULTS: 7/8 starter cultures produced mutagenic (>100 MUmol/L) levels of
      acetaldehyde and 4/8 starter cultures produced more than 1,000 MUmol/L of
      acetaldehyde. The highest alcohol levels (mean 79.4 mmol/L) were detected in the
      four fermented milks with highest acetaldehyde production. The mean number of
      microbial species in the starter cultures was 5 (range 2-8). Yeasts were
      identified in all starter cultures (mean 1.5 species/milk) but their proportion
      of the total microbial count varied markedly (mean 35%, range 7%-90%). A
      combination of yeast and lactobacilli, especially Candida krusei with
      Lactobacillus kefiri, with the exclusion of other species, seemed to correlate
      with higher acetaldehyde and ethanol levels. CONCLUSIONS: Significant levels of
      ethanol and acetaldehyde were produced during mursik fermentation. IMPACT: When
      ingested several times daily the repeated exposure to carcinogenic levels of
      acetaldehyde may contribute to esophageal carcinogenesis.

PMID- 23155140
TI  - Excessive fibrin deposition in nasal polyps caused by fibrinolytic impairment
      through reduction of tissue plasminogen activator expression.
AB  - RATIONALE: Nasal polyps (NPs) are characterized by intense edema or formation of
      pseudocysts filled with plasma proteins, mainly albumin. However, the mechanisms
      underlying NP retention of plasma proteins in their submucosa remain unclear.
      OBJECTIVES: We hypothesized that formation of a fibrin mesh retains plasma
      proteins in NPs. We assessed the fibrin deposition and expression of the
      components of the fibrinolytic system in patients with chronic rhinosinusitis
      (CRS). METHODS: We assessed fibrin deposition in nasal tissue from patients with
      CRS and control subjects by means of immunofluorescence. Fibrinolytic components,
      d-dimer, and plasminogen activators were measured using ELISA, real-time PCR, and
      immunohistochemistry. We also performed gene expression and protein
      quantification analysis in cultured airway epithelial cells. MEASUREMENTS AND
      MAIN RESULTS: Immunofluorescence data showed profound fibrin deposition in NP
      compared with uncinate tissue (UT) from patients with CRS and control subjects.
      Levels of the cross-linked fibrin cleavage product protein, d-dimer, were
      significantly decreased in NP compared with UT from patients with CRS and control
      subjects, suggesting reduced fibrinolysis (P < 0.05). Expression levels of tissue
      plasminogen activator (t-PA) mRNA and protein were significantly decreased in NP
      compared with UT from patients with CRS and control subjects (P < 0.01).
      Immunohistochemistry demonstrated clear reduction of t-PA in NP, primarily in the
      epithelium and glands. Th2 cytokine-stimulated cultured airway epithelial cells
      showed down-regulation of t-PA, suggesting a potential Th2 mechanism in NP.
      CONCLUSIONS: A Th2-mediated reduction of t-PA might lead to excessive fibrin
      deposition in the submucosa of NP, which might contribute to the tissue
      remodeling and pathogenesis of CRS with nasal polyps.

PMID- 23155141
TI  - Endothelial progenitor cells in acute myocardial infarction and sleep-disordered
      breathing.
AB  - RATIONALE: Mobilization and functions of endothelial progenitor cells (EPCs) are
      increased in patients with acute myocardial infarction (AMI). Yet, sleep
      disordered breathing (SDB) is highly prevalent in patients with AMI. OBJECTIVES:
      To compare EPC numbers and functions in patients with AMI with SDB (AMI-SDB) and
      without SDB (AMI-only) and to determine the effects of intermittent hypoxia (IH)
      in vitro on EPC proliferative and angiogenic properties. METHODS: Forty male
      patients with AMI underwent a whole-night sleep study using ambulatory
      monitoring. Nineteen had SDB (oxygen desaturation index > 5 events/h). AMI-SDB
      and AMI-only patients were matched by age, body mass index, blood chemistry, and
      comorbidities. Blood samples were analyzed by flow cytometry, endothelial cell
      colony-forming units (EC-CFU), paracrine measures, blood chemistry, and oxidative
      stress, inflammatory, and angiogenic markers. Effects of IH in vitro were studied
      in 12 healthy subjects. MEASUREMENTS AND MAIN RESULTS: Circulating EPCs
      (CD34(+)/KDR(+)), angiogenic T cells (CD3(+)/CD31(+)/CXCR4(+)), and vascular
      endothelial growth factor in monocytes were significantly higher in AMI-SDB
      patients, whereas plasma stromal cell-derived factor (SDF)-1alpha levels were
      significantly lower. Also, EC-CFU numbers and EC-CFU paracrine effects on
      endothelial tube formation were significantly higher in AMI-SDB compared with AMI
      only patients. Similarly, in cell cultures from healthy subjects, EC-CFU numbers
      and their paracrine effects on endothelial tube formation were increased after
      exposure to IH in vitro compared with normoxia. CONCLUSIONS: Coexistent mild to
      moderate SDB in patients with AMI increased the mobilization, proliferative and
      angiogenic capacities of EPCs, angiogenic T-cell numbers, and vascular
      endothelial growth factor expression in monocytes compared with patients with AMI
      without SDB. IH in vitro had similar effects on healthy EPC functions.

PMID- 23155143
TI  - The interplay between the effects of lifetime asthma, smoking, and atopy on fixed
      airflow obstruction in middle age.
AB  - RATIONALE: The contribution by asthma to the development of fixed airflow
      obstruction (AO) and the nature of its effect combined with active smoking and
      atopy remain unclear. OBJECTIVES: To investigate the prevalence and relative
      influence of lifetime asthma, active smoking, and atopy on fixed AO in middle
      age. METHODS: The population-based Tasmanian Longitudinal Health Study cohort
      born in 1961 (n = 8,583) and studied with prebronchodilator spirometry in 1968
      was retraced (n = 7,312) and resurveyed (n = 5,729 responses) from 2002 to 2005.
      A sample enriched for asthma and chronic bronchitis underwent a further
      questionnaire, pre- and post-bronchodilator spirometry (n = 1,389), skin prick
      testing, lung volumes, and diffusing capacity measurements. Prevalence estimates
      were reweighted for sampling fractions. Multiple linear and logistic regression
      were used to assess the relevant associations. MEASUREMENTS AND MAIN RESULTS:
      Main effects and interactions between lifetime asthma, active smoking, and atopy
      as they relate to fixed AO were measured. The prevalence of fixed AO was 6.0%
      (95% confidence interval [CI], 4.5-7.5%). Its association with early-onset
      current clinical asthma was equivalent to a 33 pack-year history of smoking (odds
      ratio, 3.7; 95% CI, 1.5-9.3; P = 0.005), compared with a 24 pack-year history for
      late-onset current clinical asthma (odds ratio, 2.6; 95% CI, 1.03-6.5; P =
      0.042). An interaction (multiplicative effect) was present between asthma and
      active smoking as it relates to the ratio of post-bronchodilator FEV(1)/FVC, but
      only among those with atopic sensitization. CONCLUSIONS: Active smoking and
      current clinical asthma both contribute substantially to fixed AO in middle age,
      especially among those with atopy. The interaction between these factors provides
      another compelling reason for atopic individuals with current asthma who smoke to
      quit.

PMID- 23155144
TI  - Stakeholder priorities for comparative effectiveness research in chronic
      obstructive pulmonary disease: a workshop report.
AB  - Comparative effectiveness research (CER) is intended to address the expressed
      needs of patients, clinicians, and other stakeholders. Representatives of 54
      stakeholder groups with an interest in chronic obstructive pulmonary disease
      (COPD) participated in workshops convened by the COPD Outcomes-based Network for
      Clinical Effectiveness and Research Translation (CONCERT) over a 2-year period.
      Year 1 focused on chronic care and care coordination. Year 2 focused on acute
      care and transitions in care between healthcare settings. Discussions and
      provisional voting were conducted via teleconferences and e-mail exchanges before
      the workshop. Final prioritization votes occurred after in-person discussions at
      the workshop. We used a modified Delphi approach to facilitate discussions and
      consensus building. To more easily quantify preferences and to evaluate the
      internal consistency of rankings, the Analytic Hierarchy Process was incorporated
      in Year 2. Results of preworkshop and final workshop voting often differed,
      suggesting that prioritization efforts relying solely on requests for topics from
      stakeholder groups without in-person discussion may provide different research
      priorities. Research priorities varied across stakeholder groups, but generally
      focused on studies to evaluate different approaches to healthcare delivery (e.g.,
      spirometry for diagnosis and treatment, integrated healthcare strategies during
      transitions in care) rather than head-to-head comparisons of medications. This
      research agenda may help to inform groups intending to respond to CER funding
      opportunities in COPD. The methodologies used, detailed in the online supplement,
      may also help to inform prioritization efforts for CER in other health
      conditions.

PMID- 23155142
TI  - Pulmonary vascular complications of liver disease.
AB  - Hepatopulmonary syndrome and portopulmonary hypertension are two pulmonary
      vascular complications of liver disease. The pathophysiology underlying each
      disorder is distinct, but patients with either condition may be limited by
      dyspnea. A careful evaluation of concomitant symptoms, the physical examination,
      pulmonary function testing and arterial blood gas analysis, and
      echocardiographic, imaging, and hemodynamic studies is crucial to establishing
      (and distinguishing) these diagnoses. Our understanding of the pathobiology,
      natural history, and treatment of these disorders has advanced considerably over
      the past decade; however, the presence of either still increases the risk of
      morbidity and mortality in patients with underlying liver disease. There is no
      effective medical treatment for hepatopulmonary syndrome. Although liver
      transplantation can resolve hepatopulmonary syndrome, there appears to be worse
      survival even with transplantation. Liver transplantation poses a very high risk
      of death in those with significant portopulmonary hypertension, where targeted
      medical therapies may improve functional status and allow successful
      transplantation in a small number of select patients.

PMID- 23155146
TI  - Association between obstructive sleep apnea and cancer incidence in a large
      multicenter Spanish cohort.
AB  - RATIONALE: Obstructive sleep apnea (OSA) has been associated with increased
      cancer mortality, but whether it is also associated with cancer incidence is
      unknown. OBJECTIVES: To investigate whether OSA is associated with increased
      cancer incidence in a large clinical cohort. METHODS: A multicenter, clinical
      cohort study including consecutive patients investigated for suspected OSA
      between 2003 and 2007 in seven Spanish teaching hospitals. Apnea-hypopnea index
      (AHI) and percent nighttime with oxygen saturation less than 90% (TSat(90)) were
      used as surrogates of OSA severity, both as continuous variables and categorized
      by tertiles. Cox proportional hazards regression analyses were used to calculate
      hazard ratio (HR) and 95% confidence interval (CI) for cancer incidence after
      adjusting for confounding variables. MEASUREMENTS AND MAIN RESULTS: A total of
      4,910 patients were analyzed (median follow-up, 4.5 yr; interquartile range, 3.4
      5.2). Compared with the lower TSat(90) category (<1.2%), the adjusted hazards
      (95% CI) of cancer incidence for increasing categories were 1.58 (1.07-2.34) for
      TSat(90) 1.2-12% and 2.33 (1.57-3.46) for TSat(90) greater than 12%. Continuous
      TSat(90) was also associated with cancer incidence (adjusted HR, 1.07 [1.02-1.13]
      per 10-unit increase in TSat(90)). In stratified analyses, TSat(90) was
      associated with cancer incidence in patients younger than 65 years (adjusted HR,
      1.13 [95% CI, 1.06-1.21] per 10-unit increase in TSat(90)) and males (adjusted
      HR, 1.11 [95% CI, 1.04-1.17] per 10-unit increase in TSat(90)). AHI was not
      associated with cancer incidence in the adjusted analyses, except for patients
      younger than 65 years (adjusted HR for AHI >43 vs. <18.7, 1.66; 95% CI, 1.04
      2.64). CONCLUSIONS: Increased overnight hypoxia as a surrogate of OSA severity
      was associated with increased cancer incidence. This association seems to be
      limited to men and patients younger than 65 years of age.

PMID- 23155147
TI  - Carbapenem-sparing antibiotic regimens for infections caused by Klebsiella
      pneumoniae carbapenemase-producing K. pneumoniae in intensive care unit.
AB  - A carbapenem-sparing regimen of tigecycline plus gentamicin or colistin was
      effective for treating 24 of 26 (92%) Klebsiella pneumoniae carbapenemase
      producing K. pneumoniae infectious episodes in 22 polytrauma intensive care unit
      patients without comorbidities. The 30-day crude mortality rate was 14%. Regimens
      were considered appropriate in 12% of episodes according to the Vitek 2 System
      and in 100% based on E-test.

PMID- 23155148
TI  - Facing ubiquitous viruses: when hand washing is not enough.

PMID- 23155145
TI  - Extracorporeal membrane oxygenation for pandemic influenza A(H1N1)-induced acute
      respiratory distress syndrome: a cohort study and propensity-matched analysis.
AB  - RATIONALE: Many patients with severe acute respiratory distress syndrome (ARDS)
      caused by influenza A(H1N1) infection receive extracorporeal membrane oxygenation
      (ECMO) as a rescue therapy. OBJECTIVES: To analyze factors associated with death
      in ECMO-treated patients and the influence of ECMO on intensive care unit (ICU)
      mortality. METHODS: Data from patients admitted for H1N1-associated ARDS to
      French ICUs were prospectively collected from 2009 to 2011 through the national
      REVA registry. We analyzed factors associated with in-ICU death in ECMO
      recipients, and the potential benefit of ECMO using a propensity score-matched
      (1:1) cohort analysis. MEASUREMENTS AND MAIN RESULTS: A total of 123 patients
      received ECMO. By multivariate analysis, increasing values of age, lactate, and
      plateau pressure under ECMO were associated with death. Of 103 patients receiving
      ECMO during the first week of mechanical ventilation, 52 could be matched to non
      ECMO patients of comparable severity, using a one-to-one matching and using
      control subjects only once. Mortality did not differ between the two matched
      cohorts (odds ratio, 1.48; 95% confidence interval, 0.68-3.23; P = 0.32).
      Interestingly, the 51 ECMO patients who could not be matched were younger, had
      lower Pa(o(2))/Fi(o(2)) ratio, had higher plateau pressure, but also had a lower
      ICU mortality rate than the 52 matched ECMO patients (22% vs. 50%; P < 0.01).
      CONCLUSIONS: Under ECMO, an ultraprotective ventilation strategy minimizing
      plateau pressure may be required to improve outcome. When patients with severe
      influenza A(H1N1)-related ARDS treated with ECMO were compared with
      conventionally treated patients, no difference in mortality rates existed. The
      unmatched, severely hypoxemic, and younger ECMO-treated patients had, however, a
      lower mortality.

PMID- 23155149
TI  - Epidemiology of invasive pneumococcal disease among high-risk adults since the
      introduction of pneumococcal conjugate vaccine for children.
AB  - BACKGROUND: Certain chronic diseases increase risk for invasive pneumococcal
      disease (IPD) and are indications for receipt of 23-valent pneumococcal
      polysaccharide vaccine (PPV23). Since the pediatric introduction of 7-valent
      pneumococcal conjugate vaccine (PCV7) in 2000, incidence of IPD among adults has
      declined. The relative magnitude of these indirect effects among persons with and
      without PPV23 indications is unknown. METHODS: We evaluated IPD incidence among
      adults with and without PPV23 indications using population- and laboratory-based
      data collected during 1998-2009 and estimates of the denominator populations with
      PPV23 indications from the National Health Interview Survey. We compared rates
      before and after PCV7 use by age, race, PPV23 indication, and serotype. RESULTS:
      The proportion of adult IPD cases with PPV23 indications increased from 51%
      before to 61% after PCV7 introduction (P < .0001). PCV7-serotype IPD declined
      among all race, age, and PPV23 indication strata, ranging from 82% to 97%.
      Overall IPD rates declined in most strata, by up to 65%. However, incidence
      remained highest among adults with PPV23 indications compared with those without
      (34.9 vs 8.8 cases per 100 000 population, respectively). Apart from age >=65
      years, diabetes is now the most common indication for PPV23 (20% of all cases vs
      10% of cases in 1998-1999). CONCLUSIONS: Although IPD rates have declined among
      adults, adults with underlying conditions remain at increased risk of IPD and
      comprise a larger proportion of adult IPD cases in 2009 compared with 2000. A
      continued increase in the prevalence of diabetes among US adults could lead to
      increased burden of pneumococcal disease.

PMID- 23155150
TI  - Performances of prognostic scoring systems in patients with healthcare-associated
      pneumonia.
AB  - BACKGROUND: There are limited data on the performance of the pneumonia severity
      index (PSI) and CURB-65 (confusion, urea, respiratory rate, blood pressure, age
      >=65) score, which were originally developed for community-acquired pneumonia
      (CAP), for patients with healthcare-associated pneumonia (HCAP). METHODS: The
      performances of PSI and CURB-65 were retrospectively evaluated in patients with
      HCAP compared to patients with CAP using prospectively collected data between
      January 2008 and December 2010. RESULTS: In total, 938 patients hospitalized with
      pneumonia were eligible for this study, consisting of 519 (55%) with CAP and 419
      (45%) with HCAP. The PSI and CURB-65 scores had similar trends of increasing
      mortality with worsening risk class in both the HCAP and CAP groups. In the HCAP
      group, however, the low-risk patients identified using CURB-65 had a higher
      aggregate 30-day mortality compared with the low-risk patients identified using
      PSI. Although the performances of PSI and CURB-65 in the HCAP group showed
      similar trends to those observed in the CAP group, the estimated areas under the
      receiver operating characteristic curve for PSI (0.679, 95% confidence interval
      [CI], .619-.739) and CURB-65 (0.599, 95% CI, .522-.675) in the HCAP group were
      significantly lower than those in the CAP group (0.835, 95% CI, .768-.759 for PSI
      and .686-.832 for CURB-65). CONCLUSIONS: The performances of PSI and CURB-65 for
      predicting 30-day mortality in patients with HCAP were comparable to those in
      patients with CAP. However, the discriminatory powers of PSI and CURB-65 for 30
      day mortality were significantly lower in the HACP group than those in the CAP
      group.

PMID- 23155152
TI  - Three-dimensional modelling of the venous system by direct multislice helical
      computed tomography venography: technique, indications and results.
AB  - The aim of multislice helical computed tomography venography (CTV) is to provide
      a precise, global and three-dimensional (3D) anatomical depiction of the venous
      network of the lower limbs. A multislice and multidetector spiral CT acquisition
      of the lower limbs with contrast injection of the dorsal foot produces about 1000
      slices in 30 seconds. Dedicated volume-rendering software can compute a realistic
      and interactive 3D model of the venous system in realtime. This new tool
      furnishes an accurate 3D representation of the whole venous system of the lower
      limb with a realistic 3D model of the limbs, providing a road map of the varicose
      networks complementary to the duplex ultrasound (DUS). CTV allows a complete
      morphological study of the deep veins, including the detection of anatomical
      variations and proximal venous obstruction, not easily detectable by DUS. In the
      case of deep vein thrombosis, it has been shown to be a good diagnostic tool,
      well correlated with sonography. It also demonstrates, in some cases,
      haemodynamic patterns which are not available by DUS, particularly for perforator
      veins and congenital vascular malformations. The use of virtual reality
      techniques enables a complete anatomical study of both deep and superficial veins
      including a virtual dissection of the limbs. CTV is also a great educational tool
      to learn anatomy of the venous system and a powerful research tool to improve our
      knowledge of venous anatomy.

PMID- 23155151
TI  - Pharmacokinetic interactions between the hepatitis C virus protease inhibitor
      boceprevir and ritonavir-boosted HIV-1 protease inhibitors atazanavir, darunavir,
      and lopinavir.
AB  - BACKGROUND: Boceprevir represents a new treatment option for hepatitis C (HCV)
      infected patients, including those with HCV/human immunodeficiency virus
      coinfection; however, little is known about pharmacokinetic interactions between
      boceprevir and antiretroviral drugs. METHODS: A randomized, open-label study to
      assess the pharmacokinetic interactions between boceprevir and ritonavir-boosted
      protease inhibitors (PI/r) was conducted in 39 healthy adults. Subjects received
      boceprevir (800 mg, 3 times daily) for 6 days and then received PI/r as follows:
      atazanavir (ATV) 300 mg once daily, lopinavir (LPV) 400 mg twice daily, or
      darunavir (DRV) 600 mg twice daily, each with ritonavir (RTV) 100 mg on days 10
      31, plus concomitant boceprevir on days 25-31. RESULTS: Boceprevir decreased the
      exposure of all PI/r, with area under the concentration-time curve [AUC] from
      time 0 to the time of the last measurable sample geometric mean ratios of 0.65
      (90% confidence interval [CI], .55-.78) for ATV/r; 0.66 (90% CI, .60-.72) for
      LPV/r, and 0.56 (90% CI, .51-.61) for DRV/r. Coadministration with boceprevir
      decreased RTV AUC during a dosing interval tau (AUC(tau)) by 22%-36%. ATV/r did
      not significantly affect boceprevir exposure, but boceprevir AUC(tau) was reduced
      by 45% and 32% when coadministered with LPV/r and DRV/r, respectively. Overall,
      treatments were well tolerated with no unexpected adverse events. CONCLUSIONS:
      Concomitant administration of boceprevir with PI/r resulted in reduced exposures
      of PI and boceprevir. These drug-drug interactions may reduce the effectiveness
      of PI/r and/or boceprevir when coadministered.

PMID- 23155153
TI  - Diagnostic tests (2) - positive and negative predictive values.

PMID- 23155154
TI  - Additional information and comments to the article review citing CHIVA.

PMID- 23155157
TI  - A future forum for UK occupational health?

PMID- 23155158
TI  - Judith Leyster the young flute player 1635.

PMID- 23155159
TI  - The human spirit level.

PMID- 23155160
TI  - Why I became an occupational physician...

PMID- 23155162
TI  - Vaccinating welders against pneumonia.

PMID- 23155164
TI  - Comments on Sancini et al.

PMID- 23155165
TI  - Charmed to be sure.

PMID- 23155166
TI  - How I use it: social bookmarking.

PMID- 23155168
TI  - Wide propagation of graded signals in nonspiking neurons.
AB  - Signal processing in neuritic trees is ruled by the concerted action of passive
      and active membrane properties that, together, determine the degree of electrical
      compartmentalization of these trees. We analyzed how active properties modulate
      spatial propagation of graded signals in a pair of nonspiking (NS) neurons of the
      leech. NS neurons present a very extensive neuritic tree that mediates the
      interaction with all the excitatory motoneurons in leech ganglia. NS cells
      express voltage-activated Ca(2+) conductances (VACCs) that, under certain
      experimental conditions, evoke low-threshold spikes. We studied the distribution
      of calcium transients in NS neurons loaded with fluorescent calcium probes in
      response to low-threshold spikes, electrical depolarizing pulses, and synaptic
      inputs. The three types of stimuli evoked calcium transients of similar
      characteristics in the four main branches of the neuron. The magnitude of the
      calcium transients evoked by electrical pulses was a graded function of the
      change in NS membrane potential and depended on the baseline potential level. The
      underlying VACCs were partially inactivated at rest and strongly inactivated at 
      20 mV. Stimulation of mechanosensory pressure cells evoked calcium transients in
      NS neurons whose amplitude was a linear function of the amplitude of the
      postsynaptic response. The results evidenced that VACCs aid an efficient
      propagation of graded signals, turning the vast neuritic tree of NS cells into an
      electrically compact structure.

PMID- 23155169
TI  - Hemispheric differences in the control of limb dynamics: a link between arm
      performance asymmetries and arm selection patterns.
AB  - Human handedness has been described and measured from two perspectives:
      handedness inventories rate hand preferences, whereas other tests examine motor
      performance asymmetries. These two measurement approaches reflect a major
      controversy in a literature that defines handedness as either a preference or an
      asymmetry in sensorimotor processing. Over the past decade, our laboratory has
      developed a model of handedness based on lateralization of neural processes. This
      model attributes distinct control processes to each hemisphere, which in turn
      lead to observable interlimb sensorimotor performance asymmetries. We now
      hypothesize that arm preference, or choice, may depend on the interaction between
      sensorimotor performance asymmetries and the given task. The purpose of this
      study is to examine whether arm selection is linked to interlimb performance
      asymmetries during reaching. Right-handed subjects made choice and nonchoice
      reaches to each of eight targets (d = 3.5 cm) arranged radially (r = 13 cm)
      around a midline starting position. We displaced each cursor (one associated with
      each hand) 30 cm to the midline start circle to ensure that there were no
      hemispace-related geometric, mechanical, or perceptual biases to use either arm
      for the two midline targets. The three targets on each side of the midline
      received mostly reaches from the ipsilateral arm, a tendency previously described
      as a "hemispace bias." However, the midline targets, which were equidistant from
      each hand, received more dominant arm reaches. Dominant arm hand paths to these
      targets were straighter and more accurately directed. Inverse dynamics analyses
      revealed a more proficient dominant arm strategy that exploited intersegmental
      dynamics to a greater extent than did the nondominant arm. These findings suggest
      that sensorimotor asymmetries in dynamic coordination might explain limb choices.
      We discuss the implications of these results for theories of action selection,
      models of handedness, and models of neural lateralization.

PMID- 23155170
TI  - Cooling reduces the cutaneous afferent firing response to vibratory stimuli in
      glabrous skin of the human foot sole.
AB  - Skin on the foot sole plays an important role in postural control. Cooling the
      skin of the foot is often used to induce anesthesia to determine the role of skin
      in motor and balance control. The effect of cooling on the four classes of
      mechanoreceptor in the skin is largely unknown, and thus the aim of the present
      study was to characterize the effects of cooling on individual skin receptors in
      the foot sole. Such insight will better isolate individual receptor contributions
      to balance control. Using microneurography, we recorded 39 single nerve afferents
      innervating mechanoreceptors in the skin of the foot sole in humans. Afferents
      were identified as fast-adapting (FA) or slowly adapting (SA) type I or II (FA I
      n = 16, FA II n = 7, SA I n = 6, SA II n = 11). Receptor response to vibration
      was compared before and after cooling of the receptive field (2-20 min). Overall,
      firing response was abolished in 30% of all receptors, and this was equally
      distributed across receptor type (P = 0.69). Longer cooling times were more
      likely to reduce firing response below 50% of baseline; however, some afferent
      responses were abolished with shorter cooling times (2-5 min). Skin temperature
      was not a reliable indicator of the level of receptor activation and often became
      uncoupled from receptor response levels, suggesting caution in the use of this
      parameter as an indicator of anesthesia. When cooled, receptors preferentially
      coded lower frequencies in response to vibration. In response to a sustained
      indentation, SA receptors responded more like FA receptors, primarily coding "on
      off" events.

PMID- 23155171
TI  - Circuit mechanisms revealed by spike-timing correlations in macaque area MT.
AB  - We recorded simultaneously from pairs of motion-sensitive neurons in the middle
      temporal cortex (MT) of macaque monkeys and used cross-correlations in the timing
      of spikes between neurons to gain insights into cortical circuitry. We
      characterized the time course and stimulus dependency of the cross-correlogram
      (CCG) for each pair of neurons and of the auto-correlogram (ACG) of the
      individual neurons. For some neuron pairs, the CCG showed negative flanks that
      emerged next to the central peak during stimulus-driven responses. Similar
      negative flanks appeared in the ACG of many neurons. Negative flanks were most
      prevalent and deepest when the neurons were driven to high rates by visual
      stimuli that moved in the neurons' preferred directions. The temporal development
      of the negative flanks in the CCG coincided with a parallel, modest reduction of
      the noise correlation between the spike counts of the neurons. Computational
      analysis of a model cortical circuit suggested that negative flanks in the CCG
      arise from the excitation-triggered mutual cross-inhibition between pairs of
      excitatory neurons. Intracortical recurrent inhibition and afterhyperpolarization
      caused by intrinsic outward currents, such as the calcium-activated potassium
      current of small conductance, can both contribute to the negative flanks in the
      ACG. In the model circuit, stronger intracortical inhibition helped to maintain
      the temporal precision between the spike trains of pairs of neurons and led to
      weaker noise correlations. Our results suggest a neural circuit architecture that
      can leverage activity-dependent intracortical inhibition to adaptively modulate
      both the synchrony of spike timing and the correlations in response variability.

PMID- 23155172
TI  - Movement representation in the primary motor cortex and its contribution to
      generalizable EMG predictions.
AB  - It is well known that discharge of neurons in the primary motor cortex (M1)
      depends on end-point force and limb posture. However, the details of these
      relations remain unresolved. With the development of brain-machine interfaces
      (BMIs), these issues have taken on practical as well as theoretical importance.
      We examined how the M1 encodes movement by comparing single-neuron and
      electromyographic (EMG) preferred directions (PDs) and by predicting force and
      EMGs from multiple neurons recorded during an isometric wrist task. Monkeys moved
      a cursor from a central target to one of eight peripheral targets by exerting
      force about the wrist while the forearm was held in one of two postures. We fit
      tuning curves to both EMG and M1 activity measured during the hold period, from
      which we computed both PDs and the change in PD between forearm postures
      (DeltaPD). We found a unimodal distribution of these DeltaPDs, the majority of
      which were intermediate between the typical muscle response and an unchanging,
      extrinsic coordinate system. We also discovered that while most neuron-to-EMG
      predictions generalized well across forearm postures, end-point force measured in
      extrinsic coordinates did not. The lack of force generalization was due to
      musculoskeletal changes with posture. Our results show that the dynamics of most
      of the recorded M1 signals are similar to those of muscle activity and imply that
      a BMI designed to drive an actuator with dynamics like those of muscles might be
      more robust and easier to learn than a BMI that commands forces or movements in
      external coordinates.

PMID- 23155173
TI  - Network interneurons underlying ciliary locomotion in Hermissenda.
AB  - In the nudibranch mollusk Hermissenda, ciliary locomotion contributes to the
      generation of two tactic behaviors. Light elicits a positive phototaxis, and
      graviceptive stimulation evokes a negative gravitaxis. Two classes of light
      responsive premotor interneurons in the network contributing to ciliary
      locomotion have been recently identified in the cerebropleural ganglia.
      Aggregates of type I interneurons receive monosynaptic excitatory (I(e)) or
      inhibitory (I(i)) input from identified photoreceptors. Type II interneurons
      receive polysynaptic excitatory (II(e)) or inhibitory (II(i)) input from
      photoreceptors. The ciliary network also includes type III inhibitory (III(i))
      interneurons, which form monosynaptic inhibitory connections with ciliary
      efferent neurons (CENs). Illumination of the eyes evokes a complex inhibitory
      postsynaptic potential, a decrease of I(i) spike activity, a complex excitatory
      postsynaptic potential, and an increase of I(e) spike activity. Here, we
      characterized the contribution of identified I, II, and III(i) interneurons to
      the neural network supporting visually guided locomotion. In dark-adapted
      preparations, light elicited an increase in the tonic spike activity of II(e)
      interneurons and a decrease in the tonic spike activity of II(i) interneurons.
      Fluorescent dye-labeled type II interneurons exhibited diverse projections within
      the circumesophageal nervous system. However, a subclass of type II interneurons,
      II(e(cp)) and II(i(cp)) interneurons, were shown to terminate within the
      ipsilateral cerebropleural ganglia and indirectly modulate the activity of CENs.
      Type II interneurons form monosynaptic or polysynaptic connections with
      previously identified components of the ciliary network. The identification of a
      monosynaptic connection between I(e) and III(i) interneurons shown here suggest
      that they provide a major role in the light-dependent modulation of CEN spike
      activity underlying ciliary locomotion.

PMID- 23155174
TI  - Blinks slow memory-guided saccades.
AB  - Memory-guided saccades are slower than visually guided saccades. The usual
      explanation for this slowing is that the absence of a visual drive reduces the
      discharge of neurons in the superior colliculus. We tested a related hypothesis:
      that the slowing of memory-guided saccades was due also to the more frequent
      occurrence of gaze-evoked blinks with memory-guided saccades compared with
      visually guided saccades. We recorded gaze-evoked blinks in three monkeys while
      they performed visually guided and memory-guided saccades and compared the
      kinematics of the different saccade types with and without blinks. Gaze-evoked
      blinks were more common during memory-guided saccades than during visually guided
      saccades, and the well-established relationship between peak and average velocity
      for saccades was disrupted by blinking. The occurrence of gaze-evoked blinks was
      associated with a greater slowing of memory-guided saccades compared with
      visually guided saccades. Likewise, when blinks were absent, the peak velocity of
      visually guided saccades was only slightly higher than that of memory-guided
      saccades. Our results reveal interactions between circuits generating saccades
      and blink-evoked eye movements. The interaction leads to increased curvature of
      saccade trajectories and a corresponding decrease in saccade velocity. Consistent
      with this interpretation, the amount of saccade curvature and slowing increased
      with gaze-evoked blink amplitude. Thus, although the absence of vision decreases
      the velocity of memory-guided saccades relative to visually guided saccades
      somewhat, the cooccurrence of gaze-evoked blinks produces the majority of slowing
      for memory-guided saccades.

PMID- 23155175
TI  - Local inhibition modulates learning-dependent song encoding in the songbird
      auditory cortex.
AB  - Changes in inhibition during development are well documented, but the role of
      inhibition in adult learning-related plasticity is not understood. In songbirds,
      vocal recognition learning alters the neural representation of songs across the
      auditory forebrain, including the caudomedial nidopallium (NCM), a region
      analogous to mammalian secondary auditory cortices. Here, we block local
      inhibition with the iontophoretic application of gabazine, while simultaneously
      measuring song-evoked spiking activity in NCM of European starlings trained to
      recognize sets of conspecific songs. We find that local inhibition differentially
      suppresses the responses to learned and unfamiliar songs and enhances spike-rate
      differences between learned categories of songs. These learning-dependent
      response patterns emerge, in part, through inhibitory modulation of selectivity
      for song components and the masking of responses to specific acoustic features
      without altering spectrotemporal tuning. The results describe a novel form of
      inhibitory modulation of the encoding of learned categories and demonstrate that
      inhibition plays a central role in shaping the responses of neurons to learned,
      natural signals.

PMID- 23155176
TI  - Critical role of trkB receptors in reactive axonal sprouting and
      hyperexcitability after axonal injury.
AB  - Traumatic brain injury (TBI) causes many long-term neurological complications.
      Some of these conditions, such as posttraumatic epilepsy, are characterized by
      increased excitability that typically arises after a latent period lasting from
      months to years, suggesting that slow injury-induced processes are critical. We
      tested the hypothesis that trkB activation promotes delayed injury-induced
      hyperexcitability in part by promoting reactive axonal sprouting. We modeled
      penetrative TBI with transection of the Schaffer collateral pathway in knock-in
      mice having an introduced mutation in the trkB receptor (trkB(F616A)) that
      renders it susceptible to inhibition by the novel small molecule 1NMPP1. We
      observed that trkB activation was increased in area CA3 1 day after injury and
      that expression of a marker of axonal growth, GAP43, was increased 7 days after
      lesion. Extracellular field potentials in stratum pyramidale of area CA3 in acute
      slices from sham-operated and lesioned mice were normal in control saline.
      Abnormal bursts of population spikes were observed under conditions that were
      mildly proconvulsive but only in slices taken from mice lesioned 7-21 days
      earlier and not in slices from control mice. trkB activation, GAP43 upregulation,
      and hyperexcitability were diminished by systemic administration of 1NMPP1 for 7
      days after the lesion. Synaptic transmission from area CA3 to area CA1 recovered
      7 days after lesion in untreated mice but not in mice treated with 1NMPP1. We
      conclude that trkB receptor activation and reactive axonal sprouting are critical
      factors in injury-induced hyperexcitability and may contribute to the
      neurological complications of TBI.

PMID- 23155177
TI  - Roles for substance P and gastrin-releasing peptide as neurotransmitters released
      by primary afferent pruriceptors.
AB  - Recent studies support roles for neurokinin-1 (NK-1) and gastrin-releasing
      peptide (GRP) receptor-expressing spinal neurons in itch. We presently
      investigated expression of substance P (SP) and GRP in pruritogen-responsive
      primary sensory neurons and roles for these neuropeptides in itch signaling.
      Responses of dorsal root ganglion (DRG) cells to various pruritogens were
      observed by calcium imaging. DRG cells were then processed for SP, GRP, and
      isolectin B-4 (IB4; a marker for nonpeptidergic neurons) immunofluorescence. Of
      pruritogen-responsive DRG cells, 11.8-26.8%, 21.8-40.0%, and 21.4-26.8% were
      immunopositive for SP, GRP, and IB4, respectively. In behavioral studies, both
      systemic and intrathecal administration of a NK-1 receptor antagonist
      significantly attenuated scratching evoked by chloroquine and a protease
      activated receptor 2 agonist, SLIGRL, but not histamine, bovine adrenal medulla
      peptide 8-22 (BAM8-22), or serotonin. Systemic or intrathecal administration of a
      GRP receptor antagonist attenuated scratching evoked by chloroquine and SLIGRL
      but not BAM8-22 or histamine. The GRP receptor antagonist enhanced scratching
      evoked by serotonin. These results indicate that SP and GRP expressed in primary
      sensory neurons are partially involved as neurotransmitters in histamine
      independent itch signaling from the skin to the spinal cord.

PMID- 23155179
TI  - Relationship between electrophysiological signature and defined sensory modality
      of trigeminal ganglion neurons in vivo.
AB  - The trigeminal ganglia (TG) innervate a heterogeneous set of highly sensitive and
      exposed tissues. Weak, innocuous stimuli can evoke pain as a normal response in
      some areas such as the cornea. This observation implies, however, the capability
      of low-threshold mechanoreceptors, inducing pain in the normal condition. To
      clarify this matter, the present study correlates the electrical signature (both
      fiber conduction velocity and somatic electrical properties) with receptor field,
      mechanical threshold, and temperature responsiveness of sensory afferents
      innervating tissues with dissimilar sensitivity (skin vs. cornea) in the
      trigeminal domain. Intracellular recordings were obtained in vivo from 148
      neurons of the left TG of 62 mice. In 111 of these neurons, the peripheral
      receptor field was successfully localized: 96 of them innervated the hairy skin,
      while the remaining 15 innervated the cornea. The electrical signature was
      defined and peripheral responses correlated with tissue target. No high threshold
      neurons were found in the cornea. Moreover, the electrical signature of corneal
      afferents resembles nociceptive neurons in the skin. TG skin afferents showed
      similar membrane electrical signature and sensory modality as skin afferents from
      dorsal root ganglion, although TG afferents exhibited a shorter duration of
      afterhyperpolarization then those previously described in dorsal root ganglion.
      These data suggest than new or different ways to classify and study TG sensory
      neurons may be required.

PMID- 23155178
TI  - Alterations in upper limb muscle synergy structure in chronic stroke survivors.
AB  - Previous studies in neurologically intact subjects have shown that motor
      coordination can be described by task-dependent combinations of a few muscle
      synergies, defined here as a fixed pattern of activation across a set of muscles.
      Arm function in severely impaired stroke survivors is characterized by
      stereotypical postural and movement patterns involving the shoulder and elbow.
      Accordingly, we hypothesized that muscle synergy composition is altered in
      severely impaired stroke survivors. Using an isometric force matching protocol,
      we examined the spatial activation patterns of elbow and shoulder muscles in the
      affected arm of 10 stroke survivors (Fugl-Meyer <25/66) and in both arms of six
      age-matched controls. Underlying muscle synergies were identified using non
      negative matrix factorization. In both groups, muscle activation patterns could
      be reconstructed by combinations of a few muscle synergies (typically 4). We did
      not find abnormal coupling of shoulder and elbow muscles within individual muscle
      synergies. In stroke survivors, as in controls, two of the synergies were
      comprised of isolated activation of the elbow flexors and extensors. However,
      muscle synergies involving proximal muscles exhibited consistent alterations
      following stroke. Unlike controls, the anterior deltoid was coactivated with
      medial and posterior deltoids within the shoulder abductor/extensor synergy and
      the shoulder adductor/flexor synergy in stroke was dominated by activation of
      pectoralis major, with limited anterior deltoid activation. Recruitment of the
      altered shoulder muscle synergies was strongly associated with abnormal task
      performance. Overall, our results suggest that an impaired control of the
      individual deltoid heads may contribute to poststroke deficits in arm function.

PMID- 23155180
TI  - Association between 2 angiographic subtypes of renal artery fibromuscular
      dysplasia and clinical characteristics.
AB  - BACKGROUND: Initially based on histology, the diagnosis of renal artery
      fibromuscular dysplasia (FMD) is now based mostly on angiographic appearance
      because arterial tissue samples are rarely available. This retrospective cross
      sectional study aimed to assess the clinical relevance of a binary angiographic
      classification of FMD lesions (unifocal or multifocal) based on computed
      tomographic or magnetic resonance angiography. METHODS AND RESULTS: Adult
      patients diagnosed with FMD in a single tertiary care center for hypertension
      management were identified by screening of electronic files. FMD lesions were
      reviewed and classified according to computed tomography or magnetic resonance
      angiography as multifocal if there were at least 2 stenoses in the same arterial
      segment; otherwise, they were classified as unifocal. Of 337 patients with
      established renal artery FMD, 276 (82%) were classified as multifocal. Patients
      with unifocal and multifocal lesions differed significantly in median age at
      diagnosis of FMD (30 and 49 years) and hypertension (26 and 40 years), sex
      distribution (female:male ratio, 2:1 and 5:1), initial blood pressure (157/97 and
      146/88 mm Hg), current smoking (50% and 26%), prevalence of unilateral renal
      artery lesions (79% and 38%), presence of kidney asymmetry (33% and 10%), renal
      revascularization procedures (90% and 35%), and hypertension cure rates in
      patients who underwent revascularization (54% and 26%). CONCLUSIONS: A binary
      angiographic classification into unifocal or multifocal renal artery FMD is
      straightforward and discriminates 2 groups of patients with different clinical
      phenotypes.

PMID- 23155181
TI  - Cytochrome P450 subfamily 2J polypeptide 2 expression and circulating
      epoxyeicosatrienoic metabolites in preeclampsia.
AB  - BACKGROUND: Preeclampsia is a multisystem disorder of pregnancy, originating in
      the placenta. Cytochrome P450 (CYP)-dependent eicosanoids regulate vascular
      function, inflammation, and angiogenesis, which are mechanistically important in
      preeclampsia. METHODS AND RESULTS: We performed microarray screening of placenta
      and decidua (maternal placenta) from 25 preeclamptic women and 23 control
      subjects. The CYP subfamily 2J polypeptide 2 (CYP2J2) was upregulated in
      preeclamptic placenta and decidua. Reverse-transcription polymerase chain
      reaction confirmed the upregulation, and immunohistochemistry localized CYP2J2 in
      trophoblastic villi and deciduas at 12 weeks and term. The CYP2J2 metabolites,
      5,6-epoxyeicosatrienoic acid (EET), 14,15-EET, and the corresponding
      dihydroxyeicosatrienoic acids, were elevated in preeclamptic women compared with
      controls in the latter two thirds of pregnancy and after delivery. Stimulating a
      trophoblast-derived cell line with the preeclampsia-associated cytokine tumor
      necrosis factor-alpha enhanced CYP2J2 gene and protein expression. In 2
      independent rat models of preeclampsia, reduced uterine-perfusion rat and the
      transgenic angiotensin II rat, we observed elevated EET, dihydroxyeicosatrienoic
      acid, and preeclamptic features that were ameliorated by the CYP epoxygenase
      inhibitor N-(methylsulfonyl)-2-(2-propynyloxy)-benzenehexanamide (MsPPOH).
      Uterine arterial rings of these rats also dilated in response to MsPPOH.
      Furthermore, 5,6-EET could be metabolized to a thromboxane analog. In a bioassay,
      5,6-EET increased the beating rate of neonatal cardiomyocytes. Blocking
      thromboxane synthesis reversed that finding and also normalized large-conductance
      calcium-activated potassium channel activity. CONCLUSIONS: Our data implicate
      CYP2J2 in the pathogenesis of preeclampsia and as a potential candidate for the
      disturbed uteroplacental remodeling, leading to hypertension and endothelial
      dysfunction.

PMID- 23155182
TI  - Variation in psychosis gene ZNF804A is associated with a refined schizotypy
      phenotype but not neurocognitive performance in a large young male population.
AB  - Genetic variability within the ZNF804A gene has been recently found to be
      associated with schizophrenia and bipolar disorder, although the pathways by
      which this gene may confer risk remain largely unknown. We set out to investigate
      whether common ZNF804A variants affect psychosis-related intermediate phenotypes
      such as cognitive performance dependent on prefrontal and frontotemporal brain
      function, schizotypal traits, and attenuated psychotic experiences in a large
      young male population. Association analyses were performed using all 4 available
      self-rated schizotypy questionnaires and cognitive data retrospectively drawn
      from the Athens Study of Psychosis Proneness and Incidence of Schizophrenia
      (ASPIS). DNA samples from 1507 healthy young men undergoing induction to military
      training were genotyped for 4 previously studied polymorphic markers in the
      ZNF804A gene locus. Single-marker analysis revealed significant associations
      between 2 recently identified candidate schizophrenia susceptibility variants
      (rs1344706 and rs7597593) and a refined positive schizotypy phenotype
      characterized primarily by self-rated paranoia/ideas of reference. Nominal
      associations were noted with all positive, but not negative, schizotypy related
      factors. ZNF804A genotype effect on paranoia was confirmed at the haplotype
      level. No significant associations were noted with central indexes of sustained
      attention or working memory performance. In this study, ZNF804A variation was
      associated with a population-based self-rated schizotypy phenotype previously
      suggested to preferentially reflect genetic liability to psychosis and defined by
      a tendency to misinterpret otherwise neutral social cues and perceptual
      experiences in one's immediate environment, as personally relevant and
      significant information. This suggests a novel route by which schizophrenia
      implicated ZNF804A genetic variation may confer risk to clinical psychosis at the
      general population level. 

PMID- 23155183
TI  - Neurophysiological evidence of corollary discharge function during vocalization
      in psychotic patients and their nonpsychotic first-degree relatives.
AB  - Predictions about sensations resulting from motor acts are instantiated through
      neural mechanisms such as the corollary discharge. With each action, the
      corollary discharge provides an unconscious comparison between predicted and
      actual sensations resulting from the action; closer matches result in greater
      suppression of sensation. This mechanism is disrupted in schizophrenia (SZ) and
      may contribute to, or reflect a failure to, distinguish self- from externally
      generated experiences, a hallmark of psychosis. We asked whether disruption is
      specific to SZ or is seen in other psychotic illnesses and in first-degree
      relatives of psychotic patients. Corollary discharge function was assessed in SZ
      patients (n = 30), schizoaffective (SA) patients (n = 19), bipolar patients with
      a history of psychosis (BPP; n = 39), nonpsychotic relatives of SZ (n = 30), SA
      (n = 23), and BPP (n = 50) patients, and healthy controls (n = 43). The N1
      component of the event-related potential, reflecting auditory cortical responses
      to sounds, was elicited by speech sound onset as subjects talked and later when
      they listened to a recording of those sounds. N1 was suppressed during talking
      compared to N1 during listening, consistent with the suppressive action of the
      corollary discharge mechanism. Suppression was significantly reduced in SZ and
      BPP patients, with a similar trend in the smaller SA group. Patient groups did
      not differ, and unaffected relatives did not differ from controls or probands.
      The failure to monitor sensations resulting from self-generated actions,
      implicating corollary discharge dysfunction, may be a common feature across
      affective and nonaffective psychosis. Data from unaffected family members do not
      indicate that this is a marker of psychosis risk. 

PMID- 23155184
TI  - Diabetes or prediabetes in newly diagnosed patients with nonaffective psychosis?
      A historical and contemporary view.

PMID- 23155186
TI  - Brentuximab vedotin.
AB  - Brentuximab vedotin (SGN-35), an intravenously administered CD30-specific
      antibody-drug conjugate, has recently been approved by the U.S. Food and Drug
      Administration for two indications, including (i) patients with Hodgkin lymphoma
      relapsing after autologous stem-cell transplantation (ASCT), or after two
      multidrug regimens in patients with Hodgkin lymphoma who are not candidates for
      ASCT; and (ii) patients with systemic anaplastic large cell lymphoma (ALCL) who
      failed at least one prior multidrug chemotherapy regimen. Patients with Hodgkin
      lymphoma and ALCL treated with brentuximab vedotin showed markedly high response
      rates for a single agent, exceeding 70% and 80% for Hodgkin lymphoma and ALCL,
      respectively. The complete response rate was equally as impressive, at 34% and
      57% for Hodgkin lymphoma and ALCL, respectively. Results like these and from many
      other upcoming clinical trials, in which brentuximab vedotin is being
      investigated in the frontline setting, promise to profoundly change how we manage
      the CD30-positive lymphoproliferative malignancies. The mechanism of action,
      preclinical antitumor activity, and clinical activity of brentuximab vedotin
      against Hodgkin lymphoma, ALCL, and other CD30-expressing lymphomas are reviewed.

PMID- 23155185
TI  - Targeted delivery of paclitaxel to EphA2-expressing cancer cells.
AB  - PURPOSE: YSA is an EphA2-targeting peptide that effectively delivers anticancer
      agents to prostate cancer tumors. Here, we report on how we increased the drug
      like properties of this delivery system. EXPERIMENTAL DESIGN: By introducing non
      natural amino acids, we have designed two new EphA2 targeting peptides: YNH,
      where norleucine and homoserine replace the two methionine residues of YSA, and
      dYNH, where a D-tyrosine replaces the L-tyrosine at the first position of the YNH
      peptide. We describe the details of the synthesis of YNH and dYNH paclitaxel
      conjugates (YNH-PTX and dYNH-PTX) and their characterization in cells and in
      vivo. RESULTS: dYNH-PTX showed improved stability in mouse serum and
      significantly reduced tumor size in a prostate cancer xenograft model and also
      reduced tumor vasculature in a syngeneic orthotopic allograft mouse model of
      renal cancer compared with vehicle or paclitaxel treatments. CONCLUSION: This
      study reveals that targeting EphA2 with dYNH drug conjugates could represent an
      effective way to deliver anticancer agents to a variety of tumor types.

PMID- 23155187
TI  - Inside the black box: starting to uncover the underlying decision rules used in a
      one-by-one expert assessment of occupational exposure in case-control studies.
AB  - OBJECTIVES: Evaluating occupational exposures in population-based case-control
      studies often requires exposure assessors to review each study participant's
      reported occupational information job-by-job to derive exposure estimates.
      Although such assessments likely have underlying decision rules, they usually
      lack transparency, are time consuming and have uncertain reliability and
      validity. We aimed to identify the underlying rules to enable documentation,
      review and future use of these expert-based exposure decisions. METHODS:
      Classification and regression trees (CART, predictions from a single tree) and
      random forests (predictions from many trees) were used to identify the underlying
      rules from the questionnaire responses, and an expert's exposure assignments for
      occupational diesel exhaust exposure for several metrics: binary exposure
      probability and ordinal exposure probability, intensity and frequency. Data were
      split into training (n=10 488 jobs), testing (n=2247) and validation (n=2248)
      datasets. RESULTS: The CART and random forest models' predictions agreed with 92
      94% of the expert's binary probability assignments. For ordinal probability,
      intensity and frequency metrics, the two models extracted decision rules more
      successfully for unexposed and highly exposed jobs (86-90% and 57-85%,
      respectively) than for low or medium exposed jobs (7-71%). CONCLUSIONS: CART and
      random forest models extracted decision rules and accurately predicted an
      expert's exposure decisions for the majority of jobs, and identified
      questionnaire response patterns that would require further expert review if the
      rules were applied to other jobs in the same or different study. This approach
      makes the exposure assessment process in case-control studies more transparent,
      and creates a mechanism to efficiently replicate exposure decisions in future
      studies.

PMID- 23155188
TI  - Pattern and predictors for respiratory illnesses and symptoms and lung function
      among textile workers in Karachi, Pakistan.
AB  - OBJECTIVES: To determine pattern and predictors for respiratory illnesses and
      symptoms and lung function among textile workers in Karachi, Pakistan. METHODS:
      This was a cross-sectional survey of 372 adult male textile workers from the
      spinning and weaving sections of 15 textile mills from Karachi. Data were
      collected from November to December 2009 through a structured, pretested
      questionnaire and spirometry. RESULTS: Prevalence of byssinosis was 10.5%,
      chronic cough 7.5%, chronic phlegm 12.9%, wheeze with shortness of breath 22.3%,
      shortness of breath (grade 2) 21%, chest tightness ever 33.3%; whereas, a low
      prevalence of asthma (4%) was identified in this population. Eight per cent had
      obstructive, 8% restrictive and 2% mixed pattern of lung function abnormality.
      After controlling for potential confounders, work in the spinning section
      predicts frequent wheeze (AOR=2.0; 95% CI 1.1 to 3.5), wheeze with shortness of
      breath (AOR=1.8; 95% CI 1.0 to 3.4), and obstructive pattern on spirometry
      (AOR=2.5; 95% CI 1.0 to 6.2). Prolonged duration of work predicts breathlessness
      grade 1 (AOR=1.8; 95% CI 1.0 to 3.1) and grade 2 (AOR=2.7; 95% CI 1.3 to 5.4), as
      well as decrements in Forced Expiratory Volume in the first second (FEV(1)) and
      FEV(1)/Forced Vital Capacity ratio. Lack of education predicts frequent wheeze
      (AOR=2.0; 95% CI 1.2 to 3.3), and Sindhi ethnicity predicts chest tightness apart
      from during cold (AOR=2.7; 95% CI 1.1 to 6.6). CONCLUSIONS: This study highlights
      the burden of respiratory illnesses and symptoms, and a low prevalence of asthma
      among textile workers in Karachi. Work in the spinning section, lack of
      education, prolonged duration of work and Sindhi ethnicity, were identified as
      important risk factors.

PMID- 23155189
TI  - Household solid fuel use and pulmonary function in an urban population in
      Shanghai, China.
AB  - OBJECTIVES: We examined the association between household solid fuel exposure and
      lung function in a densely populated district in urban Shanghai, China. METHODS:
      Spirometry was performed in 12 506 subjects, aged 18 and over, residing in the
      Putuo District in Shanghai, China, in a cross-sectional survey. Exposure to solid
      fuel use at home was assessed by an administered questionnaire, estimating
      duration and total amount of solid fuel use at home during the lifetime. RESULTS:
      After adjusting for confounders, the subjects with exposure to household solid
      fuel had a 1.3% (95% CI 0.57 to 2.02) decrease in forced expiratory volume in 1 s
      (FEV(1)) percent predicted and 3.5% (95% CI 2.74 to 4.18) decrease in forced
      vital capacity (FVC) percent predicted, respectively. Trends towards decreased
      pulmonary function measures were seen for longer duration and greater amount of
      household fuel use at home, in the highest compared with lowest tertile (p values
      for trend <0.001). We observed decrease in FEV(1) and FVC percent predicted
      across increase in tertile of body mass index in association with in-home solid
      fuel exposure. CONCLUSIONS: This study suggests that in-home solid fuel exposure
      is associated with reduced lung function in an urban population.

PMID- 23155190
TI  - Random effects regression models for trends in standardised mortality ratios.
AB  - OBJECTIVES: Standardised mortality ratios (SMRs) play an important role in the
      epidemiological literature, particularly in evaluations of occupational hazards.
      While some authors have argued that comparisons of SMRs should be avoided, many
      investigators find such analyses appealing particularly when data are sparse. For
      example, calendar period-specific SMRs often are examined to identify emerging
      problems or to assess whether a hazard that impacted death rates in the past has
      abated. However, because the distribution of people with respect to age usually
      changes as calendar time advances, comparisons of SMRs across calendar periods
      can produce misleading results. METHODS: We propose a random effects model to
      reduce the potential bias arising from comparisons of SMRs. This approach is
      illustrated using data from a study of workers employed at the Department of
      Energy's Oak Ridge National Laboratory. RESULTS: When there is homogeneity across
      strata of covariates in the ratio of death rates in the target population to that
      in the reference population, the proposed model yields results equivalent to
      those obtained by a classical analysis of SMRs. However, as evidence against such
      homogeneity increases, the model yields a random effects version of SMRs for
      which patterns will conform better to those obtained from an internal analysis of
      rate ratios. CONCLUSIONS: The proposed random effects model can reduce potential
      bias arising in the comparisons of SMRs.

PMID- 23155191
TI  - Migraine and restless legs syndrome in men.
AB  - BACKGROUND: Previous studies suggest an association between migraine and restless
      legs syndrome (RLS). Population-based data, however, have been limited to women.
      The aim of this study is to evaluate the association between migraine and RLS in
      a male cohort. METHODS: We conducted a cross-sectional study among 22,926
      participants in the Physicians' Health Study. Migraine and RLS information was
      self-reported. RLS was classified according to four minimal diagnostic criteria.
      Age- and multivariable-adjusted logistic regression models were calculated.
      RESULTS: Of the 22,926 participants (mean age 67.8), 2816 (12.3%) reported
      migraine and 1717 (7.5%) RLS. Migraine was associated with an increased
      multivariable-adjusted odds ratio (OR) (95% confidence interval (CI)) of 1.20
      (1.04-1.38) for having RLS. The association remained stable after excluding men
      with potential mimics of RLS and was not modified by age. CONCLUSIONS: Results of
      our study indicate an association between migraine and RLS in men. The magnitude
      of effect is similar to what has been reported in women.

PMID- 23155192
TI  - Continuing on . . . Hemicrania continua.

PMID- 23155193
TI  - NXN-188, a selective nNOS inhibitor and a 5-HT1B/1D receptor agonist, inhibits
      CGRP release in preclinical migraine models.
AB  - BACKGROUND: NXN-188 is a combined neuronal nitric oxide synthase (nNOS) inhibitor
      and 5-hydroxytryptamine 1B/1D (5-HT1B/1D) receptor agonist. Using preclinical
      models, we evaluated whether these two unique therapeutic principles have a
      synergistic effect in attenuating stimulated calcitonin gene-related peptide
      (CGRP) release, a marker of trigeminal activation. METHODS: We examined the
      effect of NXN-188 on: (1) KCl-, capsaicin- and resiniferatoxin (RTX)-induced
      immunoreactive CGRP (iCGRP) release from isolated preparation of rat dura mater,
      trigeminal ganglion (TG) and trigeminal nucleus caudalis (TNC); and (2) capsaicin
      and electrical stimulation (ES)-induced middle meningeal artery (MMA) dilation
      in a rat closed-cranial window. RESULTS: NXN-188 inhibited: (1) KCl-stimulated
      iCGRP release from dura mater (% decrease mean +/- SEM, lowest effective
      concentration) (35 +/- 6%, 30 uM), TG (24 +/- 11%, 10 uM) and TNC (40 +/- 8%, 10
      uM); (2) capsaicin- and RTX-induced iCGRP release from dura mater; and (3)
      capsaicin- and ES-induced increase in dural artery diameter (32 +/- 5%, 3 mg kg(
      1) intravenous (i.v.) and 36 +/- 1%, 10 mg kg(-1) i.v.). CONCLUSIONS: NXN-188
      inhibits CGRP release from migraine-relevant cephalic tissues. Its effect is most
      likely mediated via a combination of nNOS-inhibition and 5-HT1B/1D receptor
      agonism in dura mater while the mechanisms of action for inhibition of CGRP
      release from TG and TNC have to be investigated further.

PMID- 23155194
TI  - Are children still at risk for lead poisoning?
AB  - BACKGROUND: The prevalence of elevated blood lead levels (EBLLs) has decreased
      nationally, creating challenges in identifying children at risk. METHODS: In a
      community known to have lead hazards, we screened children with a field
      administered capillary blood lead test and asked parents to complete a
      questionnaire about lead risk factors. RESULTS: Of the 77 child-parent pairs
      screened with a blood lead test and a parental questionnaire, 4 had finger stick
      blood lead levels of >=10 ug/dL. Of these, one child had a confirmatory venous
      blood lead level >10 ug/dL (1.3%; 95% CI = 0.0%-4.7%), which is near the US
      prevalence but less than the historic prevalence for this region. A median of 2
      risk factors for each of the environmental, behavioral, and knowledge/awareness
      domains were noted. CONCLUSIONS: Despite a low prevalence of children with EBLL,
      parental report suggested that approximately 29% of children had lead-based paint
      in their home environment.

PMID- 23155195
TI  - Outcomes of children treated with tracheostomy and positive-pressure ventilation
      at home.
AB  - BACKGROUND: Long-term outcomes for children who survive on tracheostomy and
      positive-pressure ventilation (TPPV) at home are not well known. METHODS: A
      retrospective review of 20 years of clinical data at a single institution was
      performed. Outcome measures included 5-year survival, decannulation rate, and
      neurocognition. RESULTS: A total of 91 children were categorized under neuromotor
      dysfunction (52%), chronic lung disease (29%), and congenital anomalies (20%).
      The 5-year survival rates for these categories were 89% (95% confidence interval
      [CI] = 80%-99%), 76% (95% CI = 57%-100%), and 94% (95% CI = 83%-100%),
      respectively. Overall, the 5-year decannulation rate was 25% (95% CI = 14%-35%),
      with children with chronic lung disease having the highest rate (51%). It was
      found that 14% were extremely delayed in neurocognition. CONCLUSION: Most
      children on TPPV at home survive beyond 5 years, and a significant number are
      decannulated. Primary care physicians and communities should be prepared to
      accommodate the increasing number of children on TPPV at home.

PMID- 23155196
TI  - New-style liquid detergent packs present new danger to children.

PMID- 23155197
TI  - Major depression and first-time hospitalization with ischemic heart disease,
      cardiac procedures and mortality in the general population: a retrospective
      Danish population-based cohort study.
AB  - OBJECTIVE: We investigated the association between unipolar depression and
      incident hospital admissions due to ischemic heart disease, invasive cardiac
      procedures and mortality independent of other medical illnesses. METHODS: A
      population-based cohort of 4.6 million persons aged 15 years or older and born in
      Denmark was followed up from 1995-2009. Incidence rate ratio (IRR) and mortality
      rate ratio (MRR) were estimated by survival analysis, stratified by or adjusted
      for gender, age, severe chronic somatic comorbidity and calendar time. RESULTS:
      Adjusted risks of cardiac hospital admissions and death were significantly
      increased by up to 15% and 68%, respectively, in persons with hospital admissions
      due to depression, and were most increased in 15-59 year old women (IRR: 1.64;
      MRR: 2.57) and men with depression (IRR: 1.39; MRR: 2.21), and during the first
      180 days after being diagnosed with depression (women: IRR: 1.38; MRR: 2.35; men:
      IRR: 1.42; MRR: 2.67). One-year mortality after new ischemic heart disease was
      elevated by 34% in women and men. By contrast, overall rates of invasive cardiac
      procedures following cardiac hospitalizations were significantly decreased by 34%
      in persons with depression but were twofold increased in men recently diagnosed
      with depression. CONCLUSION: Clinical depression leading to hospitalization was a
      risk factor for new cardiac complications independent of somatic comorbidity in
      the magnitude of other cardiac risk factors, particularly in individuals between
      15-59 years of age and during the first weeks following psychiatric admission.
      Our findings support recent cardiovascular disease prevention guidelines on
      assessing depression among other psychosocial factors in patients at increased
      cardiovascular disease (CVD) risk.

PMID- 23155198
TI  - Polychlorinated biphenyls impair blood-brain barrier integrity via disruption of
      tight junction proteins in cerebrum, cerebellum and hippocampus of female Wistar
      rats: neuropotential role of quercetin.
AB  - Polychlorinated biphenyls (PCBs) comprise a ubiquitous class of toxic substances
      associated with carcinogenic and tumor-promoting effects as well as neurotoxic
      properties. Reactive oxygen species, which is produced from PCBs, alters blood
      brain barrier (BBB) integrity, which is paralleled by cytoskeletal rearrangements
      and redistribution and disappearance of tight junction proteins (TJPs) like
      claudin-5 and occludin. Quercetin, a potent antioxidant present in onion and
      other vegetables, appears to protect brain cells against oxidative stress, a
      tissue-damaging process associated with Alzheimer's and other neurodegenerative
      disorders. The aim of this study is to analyze the role of quercetin on oxidative
      stress markers and transcription of transmembrane and cytoplasmic accessory TJPs
      on cerebrum, cerebellum and hippocampus of female rats exposed to PCBs. Rats were
      divided into the following four groups. Group I: received only vehicle (corn oil)
      intraperitoneally (i.p.); group II: received Aroclor 1254 at a dose of 2 mg/kg
      body weight (bwt)/day (i.p); group III: received Aroclor 1254 (i.p.) and
      simultaneously quercetin 50 mg/kg bwt/day through gavage and group IV: received
      quercetin alone gavage. From the experiment, the levels of hydrogen peroxide,
      lipid peroxidation and thiobarbituric acid reactive substances were observed to
      increase significantly in cerebrum, cerebellum and hippocampus as 50%, 25% and
      20%, respectively, after exposure to PCB, and the messenger RNA expression of TJP
      in rats exposed to PCBs is decreased and is retrieved to the normal level
      simultaneously in quercetin-treated rats. Hence, quercetin can be used as a
      preventive medicine to PCBs exposure and prevents neurodegenerative disorders. 

PMID- 23155199
TI  - Effect of lifestyles on the blood mercury level in Korean adults.
AB  - Mercury (Hg) is widely distributed in the environment and oral exposure is a main
      route in the general population. In this study, we estimated the dietary intake
      of Hg and its relationship with blood Hg levels in Korean adults. The study
      subjects were recruited from three different districts (rural: 189, coastal: 208
      and urban: 184). We used a general questionnaire to collect information about
      demographic factors, lifestyles and diet. Dietary habits were studied using the
      24-h recall method. The estimation of Hg intake was performed using the database
      of Hg contents in 128 Korean foods based on the previous studies. Blood Hg was
      analyzed using Direct Mercury Analyzer with the gold-amalgam method. Daily intake
      of Hg by diet was estimated at 13.57 MUg (0.22 MUg/kg body weight). The geometric
      mean Hg concentration in whole blood was 3.92 MUg/L. Blood Hg level and Hg intake
      by diet was higher in coastal areas than in urban or rural areas, respectively.
      Blood Hg level correlated with the intake of Hg consumed from diet. Seafood was
      highly responsible and account for 75.6% of total dietary Hg intake. In this
      study, blood Hg concentrations were found to be significantly affected by sex,
      age, individual lifestyles and especially the amount of seafood intake, which
      might play an important role in determining blood Hg levels in Korean adults.

PMID- 23155200
TI  - Protective effects of resveratrol on sepsis-induced DNA damage in the lymphocytes
      of rats.
AB  - Sepsis, often initiated by an infection, is a state of disrupted inflammatory
      homeostasis. There is increasing evidence that oxidative stress has an important
      role in the development of sepsis-induced multiorgan failure. Resveratrol (RV) is
      a polyphenolic compound found in the skin of red fruits, such as mulberries and
      red grapes, and in peanuts. RV has been reported to have an antioxidant,
      antiproliferative, and anti-inflammatory properties in various models. It has
      also been found to inhibit the proliferation of a variety of human cancer cell
      lines, including breast, prostate, colon, pancreatic, and thyroid. This study has
      been undertaken to assess the role of RV on the sepsis-induced oxidative DNA
      damage in the lymphocytes of Wistar albino rats by the standard and
      formamidopyrimidine DNA glycosylase (Fpg)-modified comet assays. The parameters
      of tail length, tail intensity, and tail moment were evaluated for the
      determination of DNA damage. According to the study, the DNA damage was found to
      be significantly higher in the sepsis-induced rats when compared with the control
      rats (p < 0.05). The parameters were significantly decreased in the RV-treated
      sepsis-induced group when compared with the sepsis-induced group. The parameters
      in the sepsis-induced rats were found to be significantly higher in the Fpg
      modified comet assay when compared with the standard comet assay (p < 0.05), and
      RV treatment decreases the DNA damage in the sepsis-induced rats, suggesting that
      the oxidative stress is likely to be responsible for DNA damage and RV might have
      a role in the prevention of sepsis-induced oxidative DNA damage. 

PMID- 23155201
TI  - The scintigraphic evaluation and genetic correlation of joint involvements in
      pediatric patients with familial Mediterranean fever.
AB  - PURPOSE: We aimed to evaluate the articular involvements in pediatric patients
      with familial Mediterranean fever (FMF) with joint symptoms by bone scintigraphy
      and to correlate the involved joints with the gene mutations. MATERIALS AND
      METHODS: A total of 41 newly diagnosed patients in pediatric age group (28 girls
      and 13 boys; mean age 9.14 +/- 2.91 years) with joint involvement symptoms were
      included in this study. Scintigraphic images were obtained at 5th min (blood pool
      or early phase) and starting at 3 h (late phase) after (after tracer injection)
      intravenous administration of technetium-99m (99mTc)-methylendiphosphonate (MDP).
      Genomic DNA was isolated from leukocytes using standard salting out procedure.
      The sequencing data were analyzed. RESULTS: Of the 41 patients, arthritis was
      found in 21 (51.2%) patients. Of the 21 patients, there was single joint
      involvement in 15 (71.4%) patients and multiple joint involvement in six (28.6%)
      patients. The mean age of patients with joint involvement (8 +/- 2.3 years) were
      considerably lower than the patients without joint involvement (10.35 +/- 3.04
      years), and this was statistically significant (p = 0.008). The most commonly
      involved joints were ankles and knees. Multiple joint involvements were most
      frequently observed in the M694V and M694I gene mutations (16.7%). CONCLUSIONS:
      We use and recommend the bone scintigraphy in patients with FMF to determine the
      presence and distribution of arthritis, since bone scintigraphy is inexpensive,
      noninvasive, easy-to-use, and also is more sensitive in the diagnosis and
      distribution of arthritis than conventional radiological methods and clinical
      examination.

PMID- 23155202
TI  - Influence of coadministration of artemether and lumefantrine on selected plasma
      biochemical and erythrocyte oxidative stress indices in female Wistar rats.
AB  - Among the artemisinin-based combination therapy (ACT) regimens, artemisinin
      derivative, artemether in combination with lumefantrine (artemether-lumefantrine,
      AL) has achieved excellent results in the fight against malarial scourge. In this
      study, we evaluated the toxic potential of these drugs at the therapeutic doses
      in female Wistar rats. Animals were randomly divided into four groups: those
      administered 1% Tween 80 (control), those administered artemether (4 mg/kg body
      weight), those administered lumefantrine (24 mg/kg body weight), and those
      coadministered artemether (4 mg/kg body weight) and lumefantrine (24 mg/kg body
      weight). The drugs were orally administered twice daily for 3 days by gastric
      intubation after which selected plasma biochemical indices, and erythrocytes
      antioxidant defence and lipid peroxidation markers were evaluated.
      Coadministration of artemether and lumefantrine raised liver and renal function
      markers and increased atherogenic index. While reduced glutathione, glucose-6
      phosphate dehydrogenase (G6PD) and catalase activities were reduced, glutathione
      peroxidase and glutathione-s-transferase activities increased in all the treated
      groups compared to the control group. The drugs caused significant (p < 0.05)
      elevation of malondialdehyde (MDA) levels compared to the control group. These
      results imply that coadministration of artemether and lumefantrine may increase
      the risks of atherosclerosis as well as liver and renal function impairments in
      the users. In addition, the drugs may also promote oxidative stress in the
      erythrocytes.

PMID- 23155203
TI  - Coma blisters in children: case report and review of the literature.
AB  - Coma-induced blisters is a rare condition associated with prolonged impairment of
      conscious level, which is relatively well-known in adults following overdose with
      barbiturates. However, it has been very rarely described in children. A case of
      coma-bullae occurring in an 11-year-old child with meningoencephalitis is herein
      reported. The bullous lesions occurred on the limbs and trunks, and evolved into
      necrotic ulcers in a few days. No correlation with any drug overdosage was found.
      A skin biopsy revealed epidermal and eccrine sweat gland necrosis with abundant
      neutrophils, and thrombosis of the vessels in the lower dermis. A comprehensive
      review of the literature showed that only 5 cases of coma-bullae in children have
      been published so far. Coma blistering resolves spontaneously within days or
      weeks. Diagnosis of coma-bullae may require careful clinical-pathologic
      correlation to exclude other blistering diseases in children. 

PMID- 23155204
TI  - White matter changes in an untreated, newly diagnosed case of classical
      homocystinuria.
AB  - The authors report the case of a 4-year-old boy who developed progressive
      unilateral weakness and developmental delays prior to his diagnosis of classical
      homocystinuria. Magnetic resonance imaging (MRI) of the brain demonstrated
      diffuse white matter changes, raising the concern for a secondary diagnosis
      causing leukoencephalopathy, since classical homocystinuria is not typically
      associated with these changes. Other inborn errors of the transsulfuration
      pathway have been reported as causing these changes. Once begun on therapy for
      his homocystinuria, his neurologic deficits resolved and his delays rapidly
      improved. Repeat MRI performed one year after instating therapy showed resolution
      of his white matter abnormalities. This case illustrates the need to consider
      homocystinuria and other amino acidopathies in the differential diagnosis of
      childhood white matter diseases and lends weight to the hypothesis that
      hypermethioninemia may induce white matter changes. 

PMID- 23155205
TI  - Childhood polyarteritis nodosa presenting with central nervous system
      manifestations and the posterior reversible encephalopathy syndrome.
AB  - Polyarteritis nodosa is a systemic necrotizing vasculitis involving medium-sized
      muscular arteries. Polyneuropathy is the only neurologic manifestation included
      in the pediatric classification schema. Central nervous system manifestations
      include infarction, hemorrhage, and encephalitis. We report on a 13-year-old
      female whose initial presentation of polyarteritis nodosa included hypertension,
      seizures, and neuroimaging findings of vasogenic edema and posterior reversible
      encephalopathy syndrome. Posterior reversible encephalopathy syndrome has been
      reported in association with renal disease, transplantation, autoimmunity, and
      cytotoxic medications. Posterior reversible encephalopathy syndrome outcomes are
      usually favorable with supportive care and treatment of the underlying etiology.
      The patient's neurologic condition improved after treatment of hypertension.
      Hypertension, posterior reversible encephalopathy syndrome, and abdominal pain
      led to a diagnostic workup. A systemic vasculitis was confirmed after detection
      of a perinephric hematoma and intrarenal aneurysms. This is a novel case of
      posterior reversible encephalopathy syndrome as an initial manifestation of
      pediatric polyarteritis nodosa. 

PMID- 23155206
TI  - Cognitive impairment occurs in children and adolescents with multiple sclerosis:
      results from a United States network.
AB  - In the largest sample studied to date, we measured cognitive functioning in
      children and adolescents with pediatric multiple sclerosis (n = 187) as well as
      those with clinically isolated syndrome (n = 44). Participants were consecutively
      enrolled from six United States Pediatric Multiple Sclerosis Centers of
      Excellence. Participants had a mean of 14.8 +/- 2.6 years of age and an average
      disease duration of 1.9 +/- 2.2 years. A total of 65 (35%) children with multiple
      sclerosis and 8 (18%) with clinically isolated syndrome met criteria for
      cognitive impairment. The most frequent areas involved were fine motor
      coordination (54%), visuomotor integration (50%), and speeded information
      processing (35%). A diagnosis of multiple sclerosis (odds ratio = 3.60,
      confidence interval = 1.07, 12.36, P = .04) and overall neurologic disability
      (odds ratio = 1.47, confidence interval = 1.10, 2.10, P = .03) were the only
      independent predictors of cognitive impairment. Cognitive impairment may occur
      early in these patients, and prompt recognition is critical for their care.

PMID- 23155207
TI  - Phenotype-based care in chronic obstructive pulmonary disease.

PMID- 23155208
TI  - Systemic inflammation in patients with chronic obstructive pulmonary disease: one
      size no longer fits all!

PMID- 23155209
TI  - Socioeconomic barriers to lung transplantation: balancing access and equity.

PMID- 23155210
TI  - Hermansky-Pudlak syndrome interstitial pneumonia: it's the epithelium, stupid!

PMID- 23155211
TI  - CD14(+)S100A9(+) myeloid-derived suppressor cells portend decreased survival in
      patients with advanced lung cancer.

PMID- 23155212
TI  - Maternal smoking during pregnancy and its effect on childhood asthma:
      understanding the puzzle.

PMID- 23155213
TI  - Evaluating the NET influence of inflammation on pneumonia biology.

PMID- 23155214
TI  - Personalized medicine: the road ahead.

PMID- 23155215
TI  - Tracheobronchial involvement in chronic eosinophilic pneumonia.

PMID- 23155216
TI  - CD64, a reliable biomarker of bacterial infection in intensive care units?

PMID- 23155217
TI  - Neutrophil CD64 expression is elevated in acetaminophen-induced acute liver
      failure.

PMID- 23155218
TI  - Pulmonary function abnormalities in children with active Crohn's disease.

PMID- 23155219
TI  - Takotsubo syndrome secondary to adrenal adenocarcinoma: cortisol as a possible
      culprit.

PMID- 23155220
TI  - Chronic pulmonary aspergillosis due to Aspergillus niger.

PMID- 23155221
TI  - Heart failure risk among patients with rheumatoid arthritis starting a TNF
      antagonist.
AB  - BACKGROUND: While heart failure (HF) is associated with elevations in tumor
      necrosis factor (TNF)alpha, several trials of TNF antagonists showed no benefit
      and possibly worsening of disease in those with known severe HF. We studied the
      risk of new or recurrent HF among a group of patients receiving these agents to
      treat rheumatoid arthritis (RA). METHODS: We used data from four different US
      healthcare programmes. Subjects with RA receiving methotrexate were eligible to
      enter the study cohort if they added or switched to a TNF antagonist or another
      non-biological disease modifying antirheumatic drug (nbDMARD). These groups were
      compared in Cox regression models stratified by propensity score decile and
      adjusted for oral glucocorticoid dosage, prior HF hospitalisations, and the use
      of loop diuretics. RESULTS: We compared 8656 new users of a nbDMARD with 11 587
      new users of a TNF antagonist with similar baseline covariates. The HR for the
      TNF antagonists compared with nbDMARD was 0.85 (95% CI 0.63 to 1.14). The HR was
      also not elevated in subjects with a history of HF. But, it was elevated prior to
      2002 (HR 2.17, 95% CI 0.45 to 10.50, test for interaction p=0.036). Oral
      glucocorticoids were associated with a dose-related gradient of HF risk: compared
      with no use, 1<=5 mg HR 1.30 (95% CI 0.91 to 1.85), >=5 mg HR 1.54 (95% CI 1.09
      to 2.19). CONCLUSIONS: TNF antagonists were not associated with a risk of HF
      hospital admissions compared with nbDMARDs in this RA population.

PMID- 23155222
TI  - Individualised aerobic and resistance exercise training improves
      cardiorespiratory fitness and reduces cardiovascular risk in patients with
      rheumatoid arthritis.
AB  - BACKGROUND AND OBJECTIVES: Low cardiorespiratory fitness (CRF) is a significant
      predictor of cardiovascular disease (CVD), and interventions aiming at increasing
      CRF are known to reduce CVD risk. The effects of such interventions on CVD risk
      have not been studied in patients with rheumatoid arthritis (RA). METHODS: 40
      age, gender, body mass index (BMI) and disease duration matched RA patients were
      allocated to either an exercise (receiving 6 months individualised aerobic and
      resistance high intensity exercise intervention, three times per week), or
      control (receiving advice on exercise benefits and lifestyle changes) arm.
      Participants were assessed at baseline, 3 and 6 months for aerobic capacity
      (VO2max), individual CVD risk factors (blood pressure, lipids, insulin
      resistance, body composition), 10-year CVD event probability and RA
      characteristics (C-reactive protein (CRP), Disease Activity Score 28 (DAS28) and
      Health Assessment Questionnaire (HAQ)). RESULTS: There were no differences
      between groups at baseline in any of the assessed variables. VO2max (p=0.001),
      blood pressure (systolic: p<0.001; diastolic: p=0.003), triglycerides (p=0.030),
      high density lipoprotein (HDL; p=0.042), total cholesterol:HDL ratio (p=0.005),
      BMI (p=0.001), body fat (p=0.026), 10-year CVD event probability (p=0.012), CRP
      (p=0.042), DAS28 (p=0.008) and HAQ (p=0.003) were all significantly improved in
      the exercise versus the control group. The change in VO2max was the strongest
      predictor for the observed improvements in all of the assessed CVD risk factors
      and disease characteristics. CONCLUSIONS: Individualised aerobic and resistance
      exercise intervention can lead to significantly improved CRF, individual CVD risk
      factors, composite CVD risk, and disease activity and severity in RA patients.

PMID- 23155223
TI  - Meta-analysis suggests that intensive non-biological combination therapy with
      step-down prednisolone (COBRA strategy) may also 'disconnect' disease activity
      and damage in rheumatoid arthritis.
AB  - BACKGROUND/OBJECTIVE: Treatment of rheumatoid arthritis (RA) with tumour necrosis
      factor (TNF) antagonists changes the relationship between disease activity and
      progression of radiological joint damage ('disconnect'): patients who have little
      or no response of disease activity still show reductions in damage progression.
      In early RA, the COBRA strategy (combination of methotrexate and sulfasalazine
      with step-down prednisolone) has been shown to be equivalent to high-dose
      methotrexate and infliximab in suppressing damage progression (BeSt trial). We
      investigated whether COBRA treatment can also 'disconnect' disease activity and
      damage. DESIGN: A meta-analysis combined data from the COBRA trial (COBRA vs
      sulfasalazine monotherapy) with that of two arms of the BeSt trial (COBRA vs
      sequential monotherapy). Linear regression related 1-year progression of damage
      (Sharp van der Heijde score) as a dependent variable with disease activity (time
      averaged Disease Activity Score in 44 joints (DAS44) or C-reactive protein
      (CRP)), treatment strategy (COBRA or control) and their interaction (indicator of
      a disconnect) as independent variables. The main outcome was the pooled
      interaction term. RESULTS: Complete data from 60-100% of patients were available.
      Before pooling, disease activity was the only (strongly) significant independent
      factor related to damage progression. The pooled interaction term was (weakly)
      significant: time-averaged DAS44*treatment interaction, one-sided p=0.027; time
      averaged CRP*treatment interaction, one-sided p=0.044. CONCLUSIONS: Changes in
      the relationship between disease activity and damage progression may not be
      limited to anti-TNF treatment, but a property of early, rapid and deep
      suppression of joint inflammation, also induced by conventional strategies that
      include glucocorticoids.

PMID- 23155224
TI  - Pre- and postoperative treatment modalities for esophageal squamous cell
      carcinoma.
AB  - BACKGROUND: The objective of this article was to review randomized clinical
      trials (RCTs) utilizing pre- and postoperative treatment modalities for
      esophageal squamous cell carcinoma (ESCC). MATERIALS AND METHODS: A computerized
      (MEDLINE) and manual search was performed to identify articles published on this
      topic between 1984 and 2012. RESULTS: We identified a total of 49 published RCTs,
      which included a total of 8,785 patients with ESCC. Treatment modalities
      consisted of pre- (n=38) and postoperative (n=11) chemo-, radio- and
      chemoradiotherapy. While both preoperative chemotherapy and chemoradiotherapy
      apparently improve R0 resection, they often result in substantial postoperative
      morbidity and mortality. Only for preoperative chemoradiotherapy does there seem
      to be a significant benefit in overall survival. CONCLUSION: R0 resection remains
      the only curative therapy for patients with ESCC. While preoperative
      chemoradiotherapy may improve overall survival, there is still the need for well
      designed RCTs, which should include a homogeneous patient collective, to clarify
      the question of definitive benefit.

PMID- 23155225
TI  - Utility of hypertension as a surrogate marker for efficacy of antiangiogenic
      therapy in NSCLC.
AB  - A plateau has been reached in the efficacy of cytotoxic chemotherapy for non
      small cell lung cancer (NSCLC), highlighting the need for novel treatments for
      this poor-prognosis malignancy. Antiangiogenic agents, including the approved
      vascular endothelial growth factor (VEGF)-targeted monoclonal antibody,
      bevacizumab, as well as a number of investigational tyrosine kinase inhibitors
      (TKIs) that simultaneously target multiple angiogenic pathways, have demonstrated
      activity in patients with NSCLC. However, unlike the epidermal growth factor
      receptor (EGFR) TKIs erlotinib and gefitinib, for which the presence of EGFR
      activating mutations are now known to predict response, no validated markers
      currently exist for the efficacy of antiangiogenic agents. Hypertension has been
      associated with antiangiogenic therapy and has also been evaluated as a surrogate
      marker for efficacy with this class of agents, although analyses, to date, have
      yielded conflicting results. This review provides a summary of currently
      available, clinically relevant data on the incidence of hypertension with VEGF
      targeted antibodies and multitargeted antiangiogenic TKIs in advanced NSCLC and
      discusses the potential predictive role of hypertension on antiangiogenic therapy
      in such patients.

PMID- 23155226
TI  - Biomarkers of pituitary neoplasms.
AB  - In a wide spectrum of tumors, cell proliferation, vascularity, apoptosis, cell
      adhesion, and cell-cycle progression may indicate tumor progression. In this
      review article, the literature regarding apoptotic markers and p53, as well as
      cyclooxygenase-2, galectin-3, and pituitary tumor-transforming factor,
      proliferative markers, angiogenesis, including vascular endothelial growth factor
      and its receptor, pituitary tumor-transforming gene, microarrays, stem cells, and
      microenvironment and tumor heterogeneity are presented. Only a particular group
      of selected biomarkers show promise in differentiating pituitary tumors which
      will behave in an aggressive manner. Therefore, the most common and promising
      biomarkers and terms were analyzed, proposing the need for uniform design and
      application of methods and standardized criteria for the interpretation of
      results. The new spectrum of biomarkers may shed light upon the pathogenetic
      mechanisms and also may serve as standardized diagnostic tool for daily
      pathologic practice.

PMID- 23155227
TI  - Recent trends in epidemiology of brain metastases: an overview.
AB  - Brain metastases (BM) are the most common intracranial neoplasm in adults.
      Initially considered as an essentially terminal stage of advanced cancer, BM are
      increasingly being recognized as an emerging area of clinical interest. Their
      epidemiological characteristics have changed significantly, including an
      increased incidence in tumors frequently associated with BM, such as lung and
      breast cancer or melanoma, but also a more frequent occurrence with other primary
      tumor entities such as renal, colorectal and ovarian cancer. BM are more commonly
      diagnosed in multiple intracerebral sites, but in the context of controlled
      extracranial disease. Accordingly, progress in the development of systemic
      treatments, together with the rationalized use of surgical resection,
      radiosurgery and whole-brain radiotherapy, have led to an increase in the number
      of long-term survivors and in median survival. The recent emergence of targeted
      therapies and growing knowledge regarding the specific biology of BM should allow
      further improvements in prognosis of this devastating disease.

PMID- 23155228
TI  - Gene expression and protein array studies of folliculin-regulated pathways.
AB  - The familial cancer syndrome Birt-Hogg-Dube syndrome is characterised by the
      development of skin (fibrofolliculomas) and renal tumours (and lung cysts) and is
      caused by mutations in the FLCN tumour suppressor gene. Though the FLCN gene
      product (folliculin) has been linked to the regulation of a variety of signalling
      pathways (e.g. the mTOR, AMPK, TGFbeta and hyoxia-responsive genes) the precise
      function of the folliculin protein is not well-defined. In order to identify
      potential novel pathways linked to folliculin function we analysed paired
      isogenic folliculin-deficient and folliculin-expressing cell lines by gene
      expression and protein (Kinexus) arrays. Gene expression microarray analysis in
      the folliculin +/- non-renal cancer line (FTC133), revealed 708 differentially
      expressed targets (fold change >2 and p<0.001) with enrichment of genes in the
      cadherin and Wnt signalling pathways. Comparison of the differentially expressed
      genes in the FTC133 datasets and previously reported gene expression data for a
      folliculin-deficient renal tumour and the UOK257 renal cell carcinoma cell line,
      revealed that RAB27B was dysregulated in all three datasets (increased expression
      in folliculin-deficient cells). The Kinexus protein array analysis suggested 73
      candidate, differentially expressed, proteins and further investigation by
      western blot analysis of 5 candidates that were also differentially expressed in
      the FTC133 gene expression microarray data, revealed that EIF2AK2 (PKR) and CASP1
      were reduced and PLCG2 was increased in folliculin-deficient FTC133 cells and in
      a BHD renal tumour. In view of the role of CASP1 in apoptosis we investigated
      whether other apoptosis-related proteins might be regulated by folliculin and
      found increased levels of SMAC/Diablo and HtrA2 in folliculin-expressing FTC133
      cells. These findings identify novel pathways and targets linked to folliculin
      tumour suppressor activity.

PMID- 23155229
TI  - Antitumor effects of synthetic 6,7-annulated-4-substituted indole compounds in
      L1210 leukemic cells in vitro.
AB  - BACKGROUND: Because annulated indoles have almost no representation in the
      PubChem or MLSMR databases, an unprecedented class of an indole-based library was
      constructed, using the indole aryne methodology, and screened for antitumor
      activity. Sixty-six novel 6,7-annulated-4-substituted indole compounds were
      synthesized, using a strategic combination of 6,7-indolyne cycloaddition and
      cross-coupling reactions under both Suzuki-Miyaura and Buchwald-Hartwig
      conditions, and tested for their effectiveness against murine L1210 tumor cell
      proliferation in vitro. MATERIALS AND METHODS: Various markers of tumor cell
      metabolism, DNA degradation, mitotic disruption, cytokinesis and apoptosis were
      assayed in vitro to evaluate drug cytotoxicity. RESULTS: Most compounds inhibited
      the metabolic activity of leukemic cells in a time- and concentration-dependent
      manner but only 9 of them were sufficiently potent to inhibit L1210 tumor cell
      proliferation by 50% in the low-MUM range after 2 (IC(50): 4.5-20.4 MUM) and 4
      days (0.5-4.0 MUM) in culture. However, the antiproliferative compounds that were
      the most effective at day 4 were not necessarily the most potent at day 2,
      suggesting different speeds of action. A 3-h treatment with antiproliferative
      annulated indole was sufficient to inhibit, in a concentration-dependent manner,
      the rate of DNA synthesis measured in L1210 cells over a 0.5-h period of pulse
      labeling with (3)H-thymidine. Four of the antiproliferative compounds had weak
      DNA-binding activities but one compound reduced the fluorescence of the ethidium
      bromide-DNA complex by up to 53%, suggesting that some annulated indoles might
      directly interact with double-stranded DNA to disrupt its integrity and prevent
      the dye from intercalating into DNA base pairs. However, all 9 antiproliferative
      compounds induced DNA cleavage at 24 h in L1210 cells, containing (3)H-thymidine
      prelabeled DNA, suggesting that these antitumor annulated indoles might trigger
      an apoptotic pathway of DNA fragmentation. Indeed the antiproliferative annulated
      indoles caused a time-dependent increase of caspase-3 activity with a peak at 6
      h. Interestingly, the compounds with the most potent antiproliferative IC(50)
      values at day 2 were consistently the most effective at inhibiting DNA synthesis
      at 3 h and inducing DNA fragmentation at 24 h. After 24-48 h, antiproliferative
      concentrations of annulated indoles increased the mitotic index of L1210 cells
      and stimulated the formation of many bi-nucleated cells, multi-nucleated cells,
      apoptotic cells and micronuclei, suggesting that these antitumor compounds might
      enhance mitotic abnormality, induce chromosomal damage or missegregation, and
      block cytokinesis to induce apoptosis. CONCLUSION: Although annulated indoles may
      have interesting bioactivity, novel derivatives with different substitutions must
      be synthesized to elucidate structure-activity relationships, identify more
      potent antitumor lead compounds, and investigate their molecular targets and
      mechanisms of action.

PMID- 23155230
TI  - The utility of tumor-specifically internalizing peptides for targeted siRNA
      delivery into human solid tumors.
AB  - BACKGROUND: Ribonucleotide reductase composed of the hRRM1 and hRRM2 subunits
      catalyzes the conversion of ribonucleotides to their corresponding deoxy forms
      for DNA replication. Anti-hRRM2 siRNA degrades hRRM2's mRNA and suppresses
      tumorigenesis. A Phase I clinical trial demonstrated its therapy potential. HN-1
      represents a tumor-specifically internalizing peptide for targeted-drug delivery
      into human head and neck squamous cell carcinoma. MATERIALS AND METHODS:
      Internalization of peptide was monitored by fluorescence microscopy. The peptide
      siRNA conjugate was chemically synthesized. The hRRM2 expression was monitored by
      western blot analysis. RESULTS: HN-1(TYR) (HN-1 with two N-terminally added
      tyrosines) was internalized by human head and neck or breast cancer cells. Anti
      hRRM2 siRNA(R) (resistant to RNase degradation) was conjugated to HN-1(TYR)
      without compromising their properties. The treatment with HN-1(TYR)-anti-hRRM2
      siRNA(R) partly suppressed the endogenously expressed hRRM2 in human breast
      cancer cells. CONCLUSION: Our results establish the utility of tumor-specifically
      internalizing peptides for targeted siRNA delivery into human cancer cells.

PMID- 23155231
TI  - Protein kinase C regulates bombesin-induced rapid VEGF secretion in neuroblastoma
      cells.
AB  - BACKGROUND: Intracellular signaling responsible for gastrin-releasing peptide
      (GRP) receptor-mediated neovascularization is not clearly understood. We sought
      to determine the cellular mechanisms involved in the GRP receptor regulation of
      vascular endothelial growth factor (VEGF) release in neuroblastoma cells.
      MATERIALS AND METHODS: BE(2)-C cells were treated with bombesin (BBS), the
      amphibian equivalent of GRP, Phorbol myristate acetate (PMA) a PKC agonist, or
      GF109293X (GFX), and analyses were performed for VEGF secretion, phosphorylated
      protein kinase B (AKT), extracellular signal-regulated kinases (ERK) and protein
      kinase D (PKD) expression. RESULTS: BBS rapidly increased VEGF secretion at 30
      min. Pre-treatment with PMA alone produced similar results; this effect was
      synergistic with the addition of GRP. Conversely, GFX blocked PMA-stimulated
      increase in VEGF secretion. Immunofluorescent staining for VEGF correlated to
      BBS, PMA and GFX. CONCLUSION: PKC is critically responsible for rapid VEGF
      secretion by GRP receptor signaling in neuroblastoma cells. Inhibition of VEGF
      significantly reduced GRP-mediated cell proliferation, suggesting its crucial
      role in neuroblastoma tumorigenesis.

PMID- 23155232
TI  - Antagonistic effect of small-molecule inhibitors of Wnt/beta-catenin in multiple
      myeloma.
AB  - BACKGROUND: Development and progression of multiple myeloma is dependent on the
      bone marrow (BM) microenvironment, and within the BM, a number of factors are
      secreted, including the Wnt ligands. Bone marrow stromal cells (BMSC) secrete Wnt
      ligands that activate Wnt signaling in multiple myeloma. The canonical Wnt
      pathway which is mediated through the transcriptional effector beta-catenin (beta
      cat) is commonly de-regulated in many cancers. Cells with active beta-cat
      regulated transcription (CRT) are protected against apoptosis; conversely,
      inhibition of CRT may prevent cell proliferation. MATERIALS AND METHODS: In this
      study, we tested the efficacy of recently described inhibitors of CRT (iCRTs;
      oxazole and thiazole) for their selective antagonistic effect on Wnt-beta-cat
      response in MM cells MM.1, U266, BMSC and primary BMMC obtained from patient
      samples (n=16). RESULTS: We demonstrated that iCRTs we used, block Wnt/beta-cat
      reporter activity, down regulate beta-cat expression and inhibit cell
      proliferation in a dose-dependent manner with an optimal dose closer to 15 MUM.
      Our data further indicate that iCRTs do not influence the expression of the
      upstream components of the Wnt pathway DKK1 at the optimal dose, suggesting that
      iCRTs may specifically target beta-cat in MM cells. Additionally, iCRT-treatment
      of MM cells, co-cultured with BMSC, showed an inhibitory effect on VEGF and cell
      migration. CONCLUSION: This study provides the first in vitro data evaluation of
      newly-described iCRTs as potential Wnt-beta-cat/VEGF pathway antagonists in
      multiple myeloma.

PMID- 23155233
TI  - Analysis of p53 and miRNA expression after irradiation of glioblastoma cell
      lines.
AB  - Glioblastoma is a malignant brain tumor that is difficult to completely cure by
      surgical treatment alone. However, resistance to anticancer drugs and radiation
      may be acquired during treatment. For instance, miRNAs involved in regulating the
      expression of genes inducing apoptosis and other specific genes have been
      proposed for use, in order to induce the apoptosis of radioresistant cancer
      cells. A172 glioblastoma cells, expressing wild-type p53 were irradiated to a
      total dose of up to 60 Gy allowing us to analyze the activities of apoptosis
      related proteins. The miR-34a expression levels in cells after irradiation at 30
      and 60 Gy were 0.17- and 18.7-times the BCL2 and caspase-9 expression levels,
      respectively. The high miR-34a expression level in the cells after irradiation at
      60 Gy reduced the p53 expression level. This study suggests that apoptosis might
      be promoted by regulating the action of miRNAs, even in cells that have acquired
      radioresistance.

PMID- 23155234
TI  - DNA methylation in ATRA-treated leukemia cell lines lacking a PML-RAR chromosome
      translocation.
AB  - A deficient retinoic acid signaling has been suggested to be an important cause
      of the clinical inefficacy of all-trans retinoic acid (ATRA) therapy in non
      promyelocytic (non-PML) forms of acute myeloid leukemia (AML). The general aim of
      the present work was to explore novel ways to take advantage of the anti-leukemic
      potential of ATRA, and, specifically, to search for a synergism between ATRA and
      epigenetic drugs. Because previous reports have found no major influence of ATRA
      on DNA methylation, we investigated whether ATRA-mediated differentiation of the
      U937 and HL-60 AML cell lines, both lacking a PML-retinoic acid receptor (RAR)
      fusion product, is accompanied by early-appearing and weak changes in CpG
      methylation. We report that in HL-60 cells, by using a highly quantitative
      analysis of a set of genes found to be abnormally expressed in AML, polymerase
      chain reaction (PCR)-amplified p16 gene promoter molecules (each with 15 CpG
      sites), exhibited a CpG methylation level of 0-4% in untreated cells, which
      increased to 4-21% after treatment with ATRA for seven days. In contrast to HL-60
      cells, U937 cells exhibited a very high CpG methylation level in p16, and ATRA
      did not influence the promoter methylation of this gene. In the total CCGG sites
      of the genome, analysed using a methylation-sensitive restriction enzyme, CpG
      methylation was significantly lower in ATRA-treated HL-60 (p<0.01) and U937 cells
      (p<0.05) than in controls. Taken together, our findings show that ATRA can
      influence DNA methylation, and suggest that future research should investigate
      whether epigenetic modulation may evoke a clinical effect of ATRA in leukemia.

PMID- 23155235
TI  - Initial activation status of the antioxidant response determines sensitivity to
      carboplatin/paclitaxel treatment of ovarian cancer.
AB  - BACKGROUND/AIM: Ovarian carcinoma is the main cause of gynecological cancer
      related deaths. The aim of this study was to determine the activation status of
      the antioxidant response in samples of ovarian serous carcinoma from paraffin
      embedded biopsies and compare them with the response of patients to carboplatin
      paclitaxel treatment. MATERIALS AND METHODS: Estrogen receptor alpha (ERalpha),
      antioxidant enzymes, and uncoupling protein (UCP) levels were analyzed by western
      blotting and the presence of estrogen receptor beta (ERbeta) was investigated by
      immunohistochemistry (IHC). RESULTS: Lower levels of ERalpha, antioxidant enzymes
      and UCPs were found in patients resistant to treatment in comparison to the
      carboplatin/paclitaxel-sensitive ones; IHC revealed a greater presence of ERbeta
      in sensitive patients. CONCLUSION: These results indicate that patients resistant
      to treatment have a lower level of antioxidant response activation compared to
      sensitive patients, fact which may be related to the efficacy of this treatment.

PMID- 23155236
TI  - In NSCLC, VEGF-A response to hypoxia may differ between squamous cell and
      adenocarcinoma histology.
AB  - AIM: To investigate if hypoxia induces vascular endothelial growth factor (VEGF)
      A and VEGF-C secretion in non-small cell lung cancer (NSCLC) cells and if the
      secretion is cell type-dependent. MATERIALS AND METHODS: Adenocarcinoma (AC)
      (H522, PAC) and squamous cell carcinoma (SCC) (H520) cell lines were exposed to
      hypoxia and normoxia. Supernatants were analysed with enzyme-linked immunosorbent
      assay (ELISA). Tissue microarrays, from 304 patients diagnosed with stage I-IIIA
      NSCLC, were immunohistochemically-stained and scored for VEGF-A and VEGF-C.
      RESULTS: In vitro, VEGF-A expression in hypoxic AC cells was significantly higher
      than that in normoxic cells (H522: p=0.004, PAC; p=0.007). In contrast, hypoxia
      led to significantly reduced VEGF-A production in the SCC cell line compared to
      normoxic cells (p=0.005). CONCLUSION: In vitro, AC and SCC exhibit different VEGF
      A responses to hypoxia. Hypoxia mediates a pro-angiogenic response in AC, but
      apparently not in SCC.

PMID- 23155237
TI  - Cytotoxicity and type of cell death induced by midazolam in human oral normal and
      tumor cells.
AB  - BACKGROUND: Intravenous anesthetics have been used during the treatment of
      various malignant tumors, however, their effects on oral tissues is not well
      understood. In the present study, the cytotoxicity of five intravenous
      anesthetics towards oral tumor and normal cells was compared. MATERIALS AND
      METHODS: Tumor specificity index was determined by the ratio of the mean 50%
      cytotoxic concentration for normal cells to that for tumor cells. Apoptosis
      induction was monitored by internucleosomal DNA fragmentation and caspase-3, -8,
      and -9 activation. Fine cell structure was observed under transmission electron
      microscopy. RESULTS: Benzodiazepines (midazolam and diazepam) exhibited higher
      cytotoxicity than barbiturates (thiopental and thiamylal), whereas propofol had
      the intermediate range of cytotoxicity. Midazolam showed the highest
      cytotoxicity. HL-60 cells were the most sensitive to midazolam, followed by
      epidermal keratinocytes, oral squamous cell carcinoma (OSCC), glioblastoma and
      then oral normal cells. Midazolam did not induce the production of apoptosis
      markers such as internucleosomal DNA fragmentation and activation of caspase-3, 
      8 and -9, but did induce the appearance of many vacuoles, mitochondrial swelling
      and cell membrane rupture in OSCC cell lines (HSC-2 and HSC-4) cells. The
      cytotoxicity of midazolam was not reduced by pre-treatment with autophagy
      inhibitors (3-methyladenine and bafilomycin A1). CONCLUSION: These results
      suggest that midazolam may induce necrotic cell death, rather than apoptosis or
      autophagy, in OSCC cell lines.

PMID- 23155238
TI  - Chemokine receptors and chemokine production by CD34+ stem cell-derived monocytes
      in response to cancer cells.
AB  - BACKGROUND: The chemokine-chemokine receptor (CR) network is involved in the
      regulation of cellular infiltration of tumours. Cancer cells and infiltrating
      macrophages produce a whole range of chemokines. This study explored the
      expression of some CR and chemokine production by cord blood stem cell-derived
      CD34(+) monocytes and their novel CD14(++)CD16(+) and CD14(+)CD16(-) subsets in
      response to tumour cells. MATERIAL AND METHODS: CR expression was determined by
      flow cytometry and their functional activity by migration to chemoattractants.
      Monocytes were cultured with tumour cells and the chemokine content was assessed
      in culture supernatants. RESULTS: CD14(++)CD16(+) monocytes exhibited increased
      expression of chemokine (C-C) receptor (CCR) 1, while CD14(+)CD16(-) of CCR2,
      chemokine (C-X-C) receptor (CXCR) 1, 2 and 4. The increased expression of CCR2 on
      CD14(+)CD16(-) monocytes was associated with their enhanced migration to monocyte
      chemoattractant protein-1 (CCL2), MCP-3 (CCL7), MCP-2 (CCL8) and MCP-4 (CCL13),
      while that of CXCR1 and 2 to interleukin 8 (CXCL8), and CXCR4 to stromal cell
      derived factor-1 (CXCL12). Tumour cells induced production of macrophage
      inflammatory protein-1alpha (CCL3) MIP-1beta and regulated on activation normal T
      cells expressed and secreted (CCL5) but not CCL2 or CXCL8, monokine induced by
      gamma interferon (CXCL9), interferon gamma-induced protein 10 (CXCL10).
      CONCLUSION: The studied monocyte subsets, in comparison to those from blood,
      exhibit different expression of CRs and response to the stimuli that occur from
      tumour cells.

PMID- 23155239
TI  - An immobilized antibody targeting N-cadherin facilitates spread of N-cadherin
      positive tumour cells.
AB  - BACKGROUND: We investigated whether an antibody targeting N-cadherin facilitates
      the adhesion and spreading of N-cadherin-positive tumour cells under static
      conditions. MATERIALS AND METHODS: Two human melanoma cell lines, HMB-2 and BLM,
      were selected for their presence and lack of expression of N-cadherin,
      respectively. In vitro adhesion experiments were performed in the presence of a
      monoclonal antibody targeting N-cadherin (GC-4) or a control (antibody to alpha
      tubulin). Quantitative data from the spreading assays were calculated by
      converting the images obtained by fluorescence microscopy to binary images.
      RESULTS: For HMB-2 cells, the average cell width was significantly larger in the
      presence of GC-4 vs. control at all measured time points, with the exception of
      the measurement at 70 minutes (p=0.051). No differences were observed between
      controls and GC-4 for BLM cells. CONCLUSION: The adhesion and spread of N
      cadherin-positive tumour cells can be facilitated by the presence of an
      immobilized antibody to N-cadherin.

PMID- 23155240
TI  - Cisplatin enhances interaction between p66Shc and HSP27: its role in
      reorganization of the actin cytoskeleton in renal proximal tubule cells.
AB  - BACKGROUND/AIM: Cisplatin nephrotoxicity includes early activation of the pro
      apoptotic p66Shc and disorganization of the actin cytoskeleton, integrity which
      is regulated by heat-shock protein-27 (Hsp27). Here we determined the potential
      role of p66Shc in abrogating the Hsp27 function. MATERIALS AND METHODS: Effects
      of p66Shc knockdown and Hsp27 overexpression on F-actin stress fibers after
      cisplatin treatment were visualized by phalloidin staining. Binding of p66Shc to
      Hsp27 after cisplatin treatment was determined by immunoprecipitation in cell and
      tissue lysates. The role of p66Shc and its Ser36 phosphorylation in Hsp27 binding
      was assessed by overexpressing it or mutating its Ser36 residue. RESULTS:
      Knockdown of p66Shc and overexpression of Hsp27 ameliorated cisplatin-mediated
      collapse of the actin cytoskeleton. Further studies revealed that p66Shc binds
      Hsp27 after treatment with cisplatin that requires Ser36 phosphorylation of
      p66Shc. CONCLUSION: We propose a novel function of p66Shc that, through
      interacting with Hsp27, accelerates cisplatin-dependent disruption of the actin
      cytoskeleton.

PMID- 23155241
TI  - MTNR1A receptor expression in normal and pathological human salivary glands.
AB  - AIM: To analyze and compare the expression of MTNR1A receptor in normal and
      pathological major and minor salivary glands. MATERIALS AND METHODS: Twenty
      samples of major and minor salivary glands and 10 with Warthin's tumor were
      studied. Expression of the MTNR1A receptor (goat polyclonal antibody raised
      against a peptide mapping at the N-terminus of MEL-1A R of human origin) was
      analyzed. RESULTS: The excretory ducts of major salivary glands demonstrated
      intense intracytoplasmic positivity but scant cytoplasmic membrane positivity for
      MTNR1A. The studied Warthin's tumors showed intense cytoplasmic positivity for
      MT1 receptor in all cylindrical epithelial cells lining spaces and a less intense
      positivity in basal cells. The lymphoid component accompanying the tumor was
      negative for MT1 receptor. CONCLUSION: Intense intracytoplasmic positivity for
      the MTNR1A receptor in the excretory ducts of human major and minor salivary
      glands and Warthin's tumor was found. The intense expression of MTNR1A receptors
      observed in this study in the excretory ducts of major and minor salivary glands
      may be related to salivary regulation.

PMID- 23155242
TI  - Non-invasive X-ray micro-computed tomographic evaluation of indomethacin on
      urethane-induced lung carcinogenesis in mice.
AB  - BACKGROUND: Lung cancer is the leading cause of cancer-related death worldwide.
      We previously reported that respiration-gated X-ray micro-computed tomography
      (micro-CT) is a useful tool for analyzing lung tumor development in animal
      models. MATERIALS AND METHODS: Lung tumors were induced by a single
      intraperitoneal injection (250 mg/kg) of urethane in male A/J mice, followed by
      indomethacin treatment at 5 ppm in the diet. The mice were scanned by micro-CT
      every 4 weeks from 10 to 26 weeks after urethane administration. RESULTS: Total
      incidence and multiplicity of lung tumors were not significantly reduced by
      indomethacin treatment, as compared with untreated mice. However, the incidence
      of adenocarcinoma tended to be reduced by indomethacin treatment. Moreover, the
      size of lung tumors, especially adenomas, was suppressed by indomethacin
      treatment. Micro-CT analysis revealed that indomethacin effectively suppressed
      tumor development after urethane treatment for 10 weeks. CONCLUSION: These
      findings indicate that indomethacin suppresses lung carcinogenesis in mice and
      micro-CT is a useful non-invasive imaging approach for evaluating the
      characteristics and suppression of lung tumors in mice treated with cancer
      chemopreventive agents.

PMID- 23155243
TI  - Phenolic diterpenes derived from Hyptis incana induce apoptosis and G(2)/M arrest
      of neuroblastoma cells.
AB  - BACKGROUND: Neuroblastoma is one of the most commonly encountered solid tumors in
      the pediatric age group, and the prognosis of patients with advanced
      neuroblastoma is very poor. In this study, the antitumor effects of five phenolic
      diterpenes derived from Hyptis incana (Lamiaceae), a Brazilian medicinal plant,
      were examined on neuroblastoma cells. MATERIALS AND METHODS: Cytotoxicity was
      assessed by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide
      (MTT) assay. Apoptotic nuclear shrinkage was monitored by Hoechst 33342 staining.
      The cell-cycle status was evaluated by flow cytometry and protein alterations
      were monitored by western blotting. Differentiated cells were photographed and
      counted in a randomized fashion. RESULTS: All of the examined compounds exhibited
      significant cytotoxicity towards the neuroblastoma cells. In particular, 7
      ethoxyrosmanol had a high degree of efficacy. Nuclear condensation and
      degradation of procaspase-3 and -9 were observed after treatment of the cells
      with these compounds. Moreover, phenolic diterpenes induced cell-cycle arrest in
      the G(2)/M phase. Rosmanol and epirosmanol tended to induce differentiation.
      CONCLUSION: Phenolic diterpenes isolated from H. incana have multiple antitumor
      effects on neuroblastoma cells.

PMID- 23155244
TI  - Marked increase of CYP24A1 mRNA level in hepatocellular carcinoma cell lines
      following vitamin D administration.
AB  - AIM: 1,25-Dihydroxyvitamin D(3) (1,25(OH)(2)D(3)) inhibits cell growth and
      induces apoptosis in numerous types of tumors. We aimed to examine the mRNA and
      protein expression of 1,25(OH)(2)D(3)-inactivating CYP24A1 and mRNA expression of
      the activating CYP27B1 enzymes, as well as that of vitamin D receptor (VDR), in
      hepatocellular carcinoma (HCC) cell cultures in response to 1,25(OH)(2)D(3)
      administration. MATERIALS AND METHODS: Increasing amounts of 1,25(OH)(2)D(3)
      (0.256-10 nM) were added to cultures of HepG2, Huh-Neo, Hep3B, Huh5-15 human HCC
      cell lines and cells then incubated for various time periods (30 min-28 h). The
      mRNA expression was analyzed by real time reverse transcription-polymerase chain
      reaction (RT-PCR). CYP24A1 protein in HepG2 cells was detected by
      immuncytochemistry. RESULTS: CYP24A1 mRNA expression significantly (p<0.0001)
      increased in response to 1,25(OH)(2)D(3) administration in two cell lines: in
      HepG2 cells, the CYP24A1 mRNA level exhibited 5,300-fold elevation, reaching a
      maximum value at 8 h; in Huh-Neo cells, the increase was 152-fold that of the
      baseline value, with the maximum being reached at 14 h. There was no significant
      change in Hep3B and Huh5-15 cell lines, nor was there any change in CYP27B1 and
      VDR gene expression in any cell cultures. Immuncytochemistry in HepG2 cells
      proved that gene activation was followed by CYP24A1 protein synthesis.
      CONCLUSION: Our novel data indicate that administration of 1,25(OH)(2)D(3)
      results in a marked increase of CYP24A1 mRNA expression in some, but not all,
      human HCC lines in vitro. These differences could be dependent upon the origin of
      the tumor cells.

PMID- 23155245
TI  - Expression of human endogenous retrovirus-K coincides with that of micro-RNA-663
      and -638 in germ-cell tumor cells.
AB  - BACKGROUND/AIM: The cell line GH was established from germ-cell tumor tissue;
      human endogenous retrovirus-K (HERV-K) expression was detectable after prolonged
      culture of the cells, particularly in cells that formed domes and vesicles. In
      addition, keeping GH cells in culture at high cell densities increased HERV-K
      expression. Here, we studied whether this inducible HERV-K expression is
      accompanied by differences in microRNA (miRNA) expression patterns of GH cells.
      MATERIALS AND METHODS: The global miRNA expression pattern of GH cell samples
      (HERV-K high versus low) was analyzed by miRNA arrays. RESULTS: Two miRNAs were
      found to be differentially regulated and to exhibit expression parallel to that
      of HERV-K. The identified miRNAs-663 and -638, have been reported to be involved
      in multiple processes, including cellular senescence. However, induction of HERV
      K expression did not change the cellular senescence status of GH cells.
      CONCLUSION: The expression of these two miRNAs might be useful as novel
      diagnostic and prognostic markers in patients with tumors.

PMID- 23155246
TI  - Interaction of MTHFR C677T and A1298C, and MTR A2756G gene polymorphisms in
      breast cancer risk in a population in Northeast Brazil.
AB  - Polymorphisms in genes encoding enzymes of folate metabolism are a focus of
      breast cancer risk studies due of the role of these enzymes in DNA methylation,
      synthesis, and repair. MTHFR, encoding for 5,10-methylenetetrahydrofolate
      reductase, is one of the most studied genes in this regard, but findings are
      controversial, and the majority of studies have analyzed polymorphisms
      individually. In this case control study, we examined the combination of the
      polymorphisms MTHFR C677T and A1298C with MTR A2756G, where MTR, methionine
      synthase, is an important enzyme of the folate cycle in the methylation pathway.
      One hundred and forty-two patients with breast cancer and controls were included
      and the genotypes were determined using PCR-RFLP. In the population studied,
      individuals carrying the polymorphic allele in the heterozygous state for both
      enzymes, MTHFR C677T and MTR A2756G, had an increased risk [odds ratio, OR=2.77
      (95% confidence interval, CI=1.19-6.52)] for disease, compared to those with the
      wild genotype. In addition, individuals carrying the MTR 2756 genotype AG had an
      increased risk when this was combined with the MTHFR 1298 genotype CC [OR=5.13
      (95% CI=0.87-38.82)]. No significant results were found from the analyses
      associating the MTHFR C677T and A1298C genotypes. However, when stratifying the
      patients by age (50 years old as the cut-off), patients over 50 years old had
      greater risk, with the presence of both MTHFR polymorphisms in the heterozygous
      state [OR=5.33 (95% CI=1.42-21.03)]. This study points out the importance of the
      interactions between the MTHFR C677T, MTHFR A1298C and MTR A2756G polymorphisms,
      and also highlights the relevance of the MTR A2756G polymorphism and age in
      breast cancer risk.

PMID- 23155247
TI  - Desensitization of NFkappaB for overcoming chemoresistance of pancreatic cancer
      cells to TNF-alpha or paclitaxel.
AB  - BACKGROUND: Chemotherapy-induced nuclear factor kappaB (NFkappaB) activation is
      thought to play a key role in acquisition of chemoresistance by cancer cells. We
      focused on blockade of this activation by using the observation so-called
      'desensitization' of NFkappaB using known NFkappaB activator, doxycycline.
      MATERIALS AND METHODS: The human pancreatic cancer cell line PANC-1 was incubated
      with doxycycline, followed by treatment with tumor necrosis factor (TNF)-alpha or
      paclitaxel. NFkappaB activity and the regulation of NFkappaB-related genes was
      analyzed. RESULTS: Doxycycline induced sustained NFkappaB activation, followed by
      desensitization to further NFkappaB activation by TNF-alpha -or paclitaxel, which
      was accompanied by decreased expression of TNF receptor p55, p75, and epidermal
      growth factor receptor. Consistent with these observations, doxycycline-pre
      treatment resulted in an augmentation of TNF-alpha- and paclitaxel-mediated
      cytotoxicity and apoptosis. CONCLUSION: These data indicate the possible clinical
      application of desensitization of NFkappaB to overcome chemoresistance by
      conventional chemotherapy for pancreatic cancer.

PMID- 23155248
TI  - Analysis of type of cell death induced by topoisomerase inhibitor SN-38 in human
      oral squamous cell carcinoma cell lines.
AB  - Despite frequent use of topoisomerase inhibitors (TIs) as antitumor agents, their
      application to oral squamous cell carcinoma (OSCC) has not been reported. We
      investigated three inhibitors of topoisomerase I [camptothecin, irinotecan, SN-38
      (active metabolite of irinotecan)] and two inhibitors of topoisomerase II
      (etoposide, teniposide) for their cytotoxicity towards a total of 15 human tumor
      cell lines and normal cultured cells. All TIs exhibited higher cytotoxicity
      towards tumor cell lines (OSCC, glioblastoma, myelogenous leukemia) as compared
      with normal mesenchymal (gingival fibroblast, pulp cell, periodontal ligament
      fibroblast) and epithelial cells (skin keratinocytes). Among TIs, SN-38 had the
      highest cytotoxicity towards OSCC cell lines, with a tumor specificity index of
      1321 compared to mesenchymal cells and 22 compared with epithelial cells. SN-38
      induced different types of cell death in two OSCC cell lines: apoptosis (caspase
      3 activation and internucleosomal DNA fragmentation) in HSC-2 cells and autophagy
      (formation of autophagosome and secondary lysosome) in HSC-4 cells. The cell
      death of HSC-2 and HSC-4 cells was significantly inhibited by pre-treatment with
      caspase inhibitor (Z-VAD-FMK) and autophagy inhibitors (3-methyladenine,
      bafilomycin A1), respectively. The present study demonstrated that SN-38 is
      highly cytotoxic to OSCC cell lines, regardless of the type of induced cell
      death, suggesting its future application for chemotherapy of OSCC.

PMID- 23155249
TI  - Suppression of cell invasion and migration by propofol are involved in down
      regulating matrix metalloproteinase-2 and p38 MAPK signaling in A549 human lung
      adenocarcinoma epithelial cells.
AB  - Metastasis is a major cause of death of patients with malignant tumors. Matrix
      metalloproteinases (MMPs) are important for the migration and invasion of various
      types of cancer cell. Propofol is a known anesthetic agent, widely used for short
      term anesthesia and for longer-term sedation. Propofol inhibits the proliferation
      of a variety of tumor cells, but there is no available information regarding
      propofol-inhibited migration and invasion of tumor cells in vitro. In this study,
      we investigated the effects of propofol on the migration and invasion of human
      lung carcinoma A549 cells. Wound healing assay and Boyden chamber assays
      indicated that propofol inhibited the migration and invasion of A549 cells in
      vitro. Gelatin zymographic analysis showed the inhibitory effect of propofol on
      the activation of expression MMP-2. Western blot analysis also indicated that
      propofol suppressed the protein expiration of growth factor receptor-bound
      protein 2 (GRB2), Jun N-terminal kinases 1/2 (p-JNK1/2), p-p38, MMP-2 and MMP-9
      in A549 cells. Results from real-time PCR assay also showed that propofol
      inhibited the mRNA gene expression of MMP-2, -7 and -9, and enhanced that of
      tissue inhibitor of metalloproteinase 1 (TIMP1) and TIMP2 in A549 cells. Taken
      together, these data show that propofol inhibits MMP-2 and -9 mRNA and protein
      expressions, resulting in suppression of lung cancer cell invasion and migration
      in vitro.

PMID- 23155250
TI  - Studies on combination of platinum drugs cisplatin and oxaliplatin with
      phytochemicals anethole and curcumin in ovarian tumour models.
AB  - Chemopreventative phytochemicals having antitumour and antioxidant properties can
      overcome problems of chemoresistance and nonspecific toxicity towards normal
      cells that are associated with platinum-based chemotherapy against cancer. These
      agents exert their effects by bringing into play numerous cellular proteins that
      in turn affect multiple steps in pathways leading to tumourigenesis. In this
      study, combinations of two cytotoxic phytochemicals anethole and curcumin were
      applied in binary combination with platinum drugs cisplatin and oxaliplatin to
      three epithelial ovarian cancer cell lines: A2780 (parent), A2780(cisR)
      (cisplatin-resistant) and A2780(ZD0473R) (ZD0473-resistant). Cell viability was
      quantified using the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium
      bromide (MTT) reduction assay and the combined drug action was analyzed based on
      the equations derived by Chou and Talalay (1984). Greatest synergism was observed
      when the phytochemical was added first followed by the platinum drug 2 h later
      and additiveness to antagonism in combined drug action was observed when the two
      compounds were administered as a bolus. If confirmed in vivo, the appropriate
      sequenced combinations of platinum with the phytochemicals may provide a means of
      overcoming drug resistance.

PMID- 23155251
TI  - Epigallocatechin gallate acts synergistically in combination with cisplatin and
      designed trans-palladiums in ovarian cancer cells.
AB  - In this study, synergism in activity from the sequenced combinations of three
      trans-palladiums (denoted as TH5, TH6 and TH7) with green tea polyphenol (-)
      epigallocatechin-3-gallate (EGCG), as well as that with cisplatin, was
      investigated in a number of human ovarian tumour models as a function of sequence
      of administration. Cellular accumulation of platinum and palladium, and the
      levels of platinum-DNA and palladium-DNA binding were also determined for the 0/4
      h and 0/0 h sequences of administration. The results of the study show that co
      administration of cisplatin with EGCG (0/0 h) produces weak synergism in both
      cisplatin-sensitive (A2780) and cisplatin-resistant (A2780(cisR)) cell lines
      whereas (0/4 h) administration produces pronounced synergism in both. In
      contrast, bolus administration of EGCG with TH5, TH6 and TH7 produces marked
      antagonism except that with TH5, in the A2780(cisR) cell line, where a mild
      synergism is observed. In the case of TH5, TH6 and TH7, administration of drugs
      with a time gap (0/4 h or 4/0 h combinations) produces sequence-dependent
      synergism in both A2780 and A2780(cisR) cell lines, whereas in the case of
      cisplatin, marked antagonism is observed with the 4/0 h sequence of
      administration in the A2780 cell line. Whereas the highly synergistic 0/4 h
      sequence of combination of cisplatin with EGCG is found to be associated with
      pronounced cellular accumulation of platinum and a high level of platinum-DNA
      binding, no such clear trend can be seen for any of the combinations of TH5, TH6
      and TH7 with EGCG. The results of the present study provide support to the idea
      that sequenced combinations of platinum drugs and tumour-active palladium
      compounds with selected phytochemicals such as EGCG may provide a means of
      overcoming drug resistance.

PMID- 23155252
TI  - Demethylation of the region around exon 2 of MLH1 gene in gastrointestinal
      cancer.
AB  - AIM: Our previous study showed that methylation of the mutL homolog 1 (MLH1)
      promoter may spread upstream from the Alu elements in intron 1. In this study, we
      investigated if the Alu methylation could also spread downstream. MATERIALS AND
      METHODS: Two colorectal cancer cell lines (RKO, SW48), and four colorectal and
      three gastric carcinomas [all Microsatellite Instability (MSI)-positive] were
      selected as cases. Normal colorectal and gastric mucosa and human peripheral
      blood, and one MSI-negative colorectal cancer case served as controls. After
      extraction of DNA, bisulfite genomic sequencing was used to analyze the
      methylation level of exon 2 and the adjacent part of intron 2 of the MLH1 gene.
      RESULTS: Exon 2 and the partial intron 2 exhibited a high level of methylation in
      controls. In contrast, demethylation in these regions was seen in
      gastrointestinal cancer. CONCLUSION: Exon 2 methylation is not likely to
      influence MLH1 gene expression. It seems that de-methylation of exon 2 and intron
      2, in combination with intron 1, is associated with methylation spreading of the
      MLH1 promoter. The region around exon 2 could possibly bind proteins that
      regulate methylation, and therefore affect gene expression.

PMID- 23155253
TI  - Dissimilar immunohistochemical expression of ERK and AKT between paired biopsy
      and hepatectomy tissues of hepatocellular carcinoma.
AB  - BACKGROUND/AIM: Biomarker studies using immunohistochemical (IHC) staining have
      not been successful for advanced hepatocellular carcinoma (HCC). We aimed to
      examine whether the tissue procurement process influences the protein expression
      levels detected by IHC. MATERIALS AND METHODS: Forty-two tissue pairs of HCC that
      had been both preoperatively biopsied and then surgically resected were included
      in the study. IHC staining was used to determine expression of target molecules,
      all of which were graded according to the percentage of positively stained tumor
      cells. The expression of beta-catenin was analyzed according to the localization
      of positive staining. RESULTS: Biopsied and surgically resected tissues exhibited
      dissimilar phosphorylated extracellular signal regulated kinase (p-ERK) and
      phosphorylated AKT expression levels (kappa=0.025 and 0.153, respectively). On
      the contrary, p53 exhibited similar expression levels, and beta-catenin exhibited
      similar staining localization patterns in biopsied and surgically resected
      tissues (kappa=0.729 and 0.654, respectively). CONCLUSION: Biopsied HCC tissues
      and their corresponding resected HCC tissues have inconsistent IHC-detected ERK
      and AKT expressions.

PMID- 23155254
TI  - MicroRNA miR-34b/c enhances cellular radiosensitivity of malignant pleural
      mesothelioma cells.
AB  - BACKGROUND: We previously reported that epigenetic silencing of microRNA-34b/c
      (miR-34b/c) plays an important role in the pathogenesis of malignant pleural
      mesothelioma (MPM). We examined the impact of miR-34b/c restoration on the
      radiosensitivity of MPM cells. MATERIALS AND METHODS: We established stable miR
      34b/c and scramble transfectants of two MPM cell lines, H2052 and H28. We
      examined these transfectants by clonogenic survival assay, phosphorylated histone
      H2AX (gammaH2AX) foci assay, cell-cycle analysis, and western blotting. RESULTS:
      The clonogenic survival assay revealed that miR-34b/c radiosensitized MPM cells.
      gammaH2AX foci assay showed that DNA double-strand break repair was delayed in
      miR-34b/c transfectants. The proportion of sub-G(1) phase cells was increased in
      miR-34b/c transfectants after irradiation. miR-34b/c inhibited expression of
      cyclin-D1, cyclin-dependent kinase 4/6, B-cell lymphoma-2 (BCL-2) and increased
      cleaved poly (ADP-ribose) polymerase (cPARP) and cleaved caspase-3 after
      irradiation. CONCLUSION: Our results indicate that miR-34b/c enhances
      radiosensitivity by promoting radiation-induced apoptosis and suggested that miR
      34b/c might be a useful therapeutic molecule to enhance radiotherapy in MPM.

PMID- 23155255
TI  - Interaction of radiation and gefitinib on a human lung cancer cell line with
      mutant EGFR gene in vitro.
AB  - AIM: To investigate the effect of gefitinib in combination with irradiation using
      HCC827 cells, a human lung cancer cell line bearing epidermal growth factor
      receptor (EGFR) mutation. MATERIALS AND METHODS: The effects of treatment with
      radiation with and without gefitinib on HCC827 cells were assessed using a
      clonogenic assay. Apoptosis was measured by flow cytometry and EGFR signal
      transduction was evaluated by western blotting. RESULTS: The Dq - quasi-threshold
      dose, the dose at which the straight portion of the survival curve, extrapolated
      backward, cuts the dose axis drawn through a survival fraction of unity - after
      radiation-alone and after combination treatment were 0.41+/-0.09 Gy and 0.08+/
      0.11 Gy, respectively; thus indicating that combination treatment resulted in
      supra-additive effects of radiation. There was no significant difference on the
      D0 - final slope of the survival curve (the dose required to reduce the fraction
      of surviving cells to 37% of its previous value) - between-radiation alone and
      the combination treatment. Apoptosis significantly increased after the
      combination treatment in comparison to what was observed after radiation-alone.
      The expression of phosphorylated EGFR (pEGFR), phosphorylated ERK1/2 (pERK1/2)
      and phosphorylated AKT (pAKT) after the combination decreased in comparison to
      what was observed after radiation-alone. CONCLUSION: Gefitinib enhances
      radiosensitivity of supra-additively HCC827 cells by inhibiting the activation of
      the anti-apoptotic and proliferative signal transduction pathways.

PMID- 23155257
TI  - Beneficial oncolytic effect of fiber-substituted conditionally replicating
      adenovirus on human lung cancer.
AB  - BACKGROUND: Adenovirus vectors have been utilized for a variety of cancer gene
      therapy. The present study examined the oncolytic effect of adenovirus type 5
      (Ad5) and fiber-substituted conditionally replicating adenovirus (CRAD) Ad5/F35
      vectors on human lung cancer A549 cells (an epithelial adenocarcinoma cell line),
      SBC-3 cells (a small-cell cancer cell line), and Lu-65 cells (a giant-cell lung
      cancer cell line). MATERIALS AND METHODS: For adenovirus, the first mRNA/protein
      to be made (~1 h after infection) is early region 1A (E1A). Ad5F35 and Ad5 CRAD
      vectors containing the E1 gene, controlled by the human midkine promoter
      (Ad5F35/MKp-E1 and Ad5/MKp-E1, respectively) were constructed. Reverse
      transcription-polymerase chain reaction (RT-PCR), western blotting and cell
      viability assays were carried out in cells transfected with Ad5/MKp-E1 and
      Ad5F35/MKp-E1. RESULTS: Less expression of mRNA and protein for coxsackie and
      adenovirus receptor (CAR), a cell surface target of Ad5, was found with lung
      cancer cells as compared with the expression in human embryonic kidney 293
      (HEK293) cells, but otherwise mRNA and CD46 protein, a cell surface target of
      Ad35, was expressed in lung cancer cells as much as in HEK293 cells. Both Ad5/MKp
      E1 and Ad5F35/MKp-E1 induced oncolysis of lung cancer cells in a viral particle
      dependent manner, with more efficient advantage for Ad5F35/MKp-E1. CONCLUSION:
      The results of the present study suggest that Ad5F35/MKp-E1 is more useful for
      the gene therapy of human lung cancer than Ad5/MKp-E1 is.

PMID- 23155256
TI  - EVI1 and MDS1/EVI1 expression during primary human hematopoietic progenitor cell
      differentiation into various myeloid lineages.
AB  - BACKGROUND AND AIM: Overexpression of ecotropic viral integration site 1 (EVI1)
      is associated with aggressive disease in myeloid leukemia. We therefore studied
      its expression and function in cluster of differentiation 34-positive (CD34(+))
      primary human hematopoietic progenitor cells. MATERIALS AND METHODS: CD34(+)
      cells were differentiated into various myeloid lineages using the appropriate
      cytokines. EVI1 expression was measured by quantitative real time reverse
      transcriptase-polymerase chain reaction (qRT-PCR) and intranuclear fluorescence
      activated cell sorting (FACS). Experimental manipulation of EVI1 levels was
      achieved using retroviral infection. RESULTS: EVI1 mRNA and its variant
      myelodysplastic syndrome 1 (MDS1)/EVI1, which gives rise to a partially
      antagonistic protein, were detectable in CD34(+) cells, but their levels declined
      rapidly during differentiation into the granulocyte, monocyte, dendritic,
      erythroid, and megakaryocyte lineages. Similarly, EVI1 protein levels decreased
      during myeloid differentiation. Attempts to experimentally express EVI1 in
      CD34(+) and U937 cells indicated that ectopic expression of EVI1 may cause growth
      arrest, apoptosis and/or senescence of human hematopoietic cells. CONCLUSION:
      EVI1 is expressed in human hematopoietic progenitor cells, but is down-regulated
      during differentiation. Ectopic expression of EVI1 may activate cellular
      safeguards against oncogene activation.

PMID- 23155258
TI  - Phenotypic analysis of monocyte-derived dendritic cells loaded with tumor antigen
      with heat-shock cognate protein-70.
AB  - BACKGROUND/AIM: The cross-presentation system of tumor antigen by monocyte
      derived dendritic cells (mo-DCs) has been observed under appropriate conditions.
      Both CD14-negative and CD1a-positive phenotypes were critical in our previous
      study. This study compared the phenotype of mo-DCs and identified the conditions
      that favored T helper-1 (Th1) cytokine production after stimulation with the
      hsc70 and NY-ESO-1 p157-165 epitope fusion protein (hsc70/ESO p157-165).
      MATERIALS AND METHODS: The mo-DCs were induced from healthy donors. Their surface
      markers and cytokine production were examined after stimulation with hsc70/ESO
      p157-165. RESULTS: CD1a(+) and CD1a(-) mo-DCs were generated in half of the
      healthy donors. The concentration of fetal calf serum in the culture medium was
      critical for the induction of CD1a(+) DCs, which were able to produce interleukin
      12 (IL-12), but not IL-10. Neutralizing IL-6 and IL-6R antibodies affected the
      expression of CD1a. CONCLUSION: Anti IL-6 analogs may be effective adjuvants for
      the development of mo-DC-based cancer vaccine.

PMID- 23155259
TI  - Primary bone lymphomas thought to be osteomyelitis urgently demand a rapid
      diagnosis in bone pathology.
AB  - We describe in detail three cases of primary bone lymphoma (PBL), initially
      treated as osteomyelitis of unknown etiology. These cases show which difficulties
      can occur with diagnosing this entity and highlight the urgent need for rapid
      diagnostic results in the field of bone pathology. Case 1: A 22-year-old man with
      the very rare diagnosis of precursor B-lymphoblastic lymphoma in the tibia
      (previously published). Case 2: A 13-year-old boy with an anaplastic large cell
      lymphoma of the "os pubis". With initial diagnosis pointing to multifocal
      osteomyelitis, histology of the left iliac crest revealed a florid/chronic
      osteomyelitis. During clinical regression with a new osteolytic lesion, he
      received treatment for chronic recurrent multifocal osteomyelitis. Case 3: A 60
      year-old man with an anaplastic large cell lymphoma of the right sacrum,
      accompanied by a putrid, florid/chronic osteomyelitis. At first, an incisional
      biopsy revealed a florid/chronic osteomyelitis-only.

PMID- 23155260
TI  - A study of serum biomarkers associated with relapse of cervical cancer.
AB  - BACKGROUND/AIM: To discover candidate protein biomarkers in the serum of patients
      with cervical cancer that differentiate between patients with relapse from those
      who are tumor-free after primary treatment with (platinum-based chemo-)
      radiation. PATIENTS AND METHODS: Surface-enhanced laser desorption/ionization
      time-of-flight mass spectrometry (SELDI-TOF-MS) with cation exchange (CM10) and
      hydrophobic/reverse-phase (H50) was used to examine 44 serum samples from
      patients with advanced cervical cancer, primarily treated with (platinum-based
      chemo-) radiation. RESULTS: Ten candidate biomarkers were identified in the serum
      of 34 patients. Six candidate markers were elevated in patients with no relapse
      and four were elevated in patients with relapse [p=0.007-0.11; area under the
      curve (AUC)=0.70-0.75]. Masses of candidate biomarkers ranged from 2,022 to
      116,165 Da. CONCLUSION: Patients with relapse from primary advanced cervical
      cancer exhibit different serum protein expression profiles from those with no
      relapse.

PMID- 23155261
TI  - Clinical utility of transarterial infusion chemotherapy using cisplatin-lipiodol
      emulsion for unresectable hepatocellular carcinoma.
AB  - BACKGROUND: We evaluated the clinical efficacy of transarterial infusion
      chemotherapy using a cisplatin-lipiodol emulsion for unresectable hepatocellular
      carcinoma (HCC). PATIENTS AND METHODS: Fifty-seven patients with advanced HCC,
      with no indications for surgical resection or local ablative therapy, such as
      percutaneous ethanol injection and radiofrequency ablation, were enrolled in this
      retrospective study. RESULTS: Twelve patients were treated with cisplatin-alone
      at a dose of 65 mg/m(2) by infusion into the artery. Forty-two patients were
      treated with the same dose of cisplatin suspended in 1-10 ml of lipiodol (C/LPD).
      Cumulative survival rates in the cisplatin-treated group were 46.2% at one year,
      and 18.5% at two years, whereas these in the C/LPD group were 81.6% and 44.4%,
      respectively, with a significant difference between the two groups (p<0.01). In
      the cisplatin-treated group (n=13), no (0%) patients had a complete response
      (CR), two (15%) a partial response (PR), three (23%) no change (NC), and eight
      (62%) progressive disease (PD). In the C/LPD group (n=44), four (9%) patients had
      CR, 16 (35%) PR, 12 (26%) NC, and 12 (26%) PD. CR and PR were seen in 15% of the
      cisplatin-treated group and in 44% of the C/LPD group. C/LPD was significantly
      more effective than cisplatin-alone (p=0.039). Some patients showed tumor
      response to C/LPD after intra-arterial infusion of low-dose 5-fluorouracil.
      CONCLUSION: C/LPD produced superior effects compared to cisplatin-alone for
      unresectable HCC, causing no major side-effects, and increasing the survival
      rate.

PMID- 23155262
TI  - Photodynamic therapy using talaporfin sodium (Laserphyrin(r)) for bile duct
      carcinoma: a preliminary clinical trial.
AB  - The efficacy of adjuvant photodynamic therapy (PDT) using the new
      photosensitizer, talaporfin sodium (TPS), was assessed in 7 patients with bile
      duct carcinoma (BDC). The 664-nm semiconductor laser (100 J/cm(2)) was applied
      through endoscopy to the tumor lesion within 6 h after injection of TPS. Cases
      included three non-resectable and 4 resected BDC with remnant cancer cells at the
      bile duct stump. Radiated lesions exhibited mild inflammatory responses. Locally
      advanced tumor occluding bile duct was relieved by PDT and patency was maintained
      for 16 months. Two patients developed mild photodermatitis but no severe
      morbidity. One patient died of other disease, and two patients died of liver
      metastasis within 6 months, but local recurrence was not observed. Three patients
      maintained cancer-free survival for 6-13 months. One patient survived with good
      status for 24 months. Adjuvant TPS-PDT is a safe and useful treatment for local
      control of BDC. Compared to the conventional PDT, the patient's quality of life
      is remarkably improved.

PMID- 23155263
TI  - Medullomyoblastoma: a case report and literature review of a rare tumor entity.
AB  - BACKGROUND: Medullomyoblastoma (MMB) is a very rare medulloblastoma (MB) variant
      consisting of primitive neuroectodermal cells intermixed with cells featuring
      myogenic differentiation. MMBs are a subtype of primitive neuroectodermal
      neoplasm (PNET) predominantly occurring in children. CASE REPORT: We describe a
      case of a one-year-old girl who presented with headache, emesis and ataxia. The
      symptoms had started seven weeks before hospital admission. Magnet resonance
      imaging of the brain was performed, and revealed a lesion with a maximal diameter
      of 5 cm, located in the cerebellum close to the vermis. Histologically, the
      poorly-differentiated lesion was diagnosed as a type of PNET, but it was the
      immunohistochemical staining that assured the diagnosis of MMB. RESULTS:
      Immunohistochemistry and interphase fluorescence in situ hybridization (I-FISH)
      were performed on formalin-fixed paraffin-embedded tissue. FISH did not reveal
      any amplification of CMYC or NMYC. No nuclear expression of beta-catenin was
      detectable. DISCUSSION: Since MMB is a very rare tumor entity, standard treatment
      today is the same as that for conventional MB due to the lack of larger study
      series. Some authors assume that MMBs behave especially aggressive in comparison
      to conventional MBs. Therefore, new treatment regimes should be tested to
      optimize the prognosis of MMB. Further data is needed to determine the
      differences between MB and MMB.

PMID- 23155264
TI  - Focus on the actual clinical target volume irradiated with intraoperative
      radiotherapy for breast cancer.
AB  - AIM: Intraoperative radiotherapy (IORT) has been investigated as an exclusive
      adjuvant treatment option for early-stage breast cancer (BC). We analysed our
      experience on the technical aspects of this innovative approach in terms of
      identification of breast volume actually to be treated during IORT. PATIENTS AND
      METHODS: A total of 315 patients at low risk of breast cancer recurrence
      underwent IORT as exclusive treatment after breast-conservative surgery. To
      evaluate the breast volume actually irradiated with IORT, we considered a sample
      of eight patients, chosen retrospectively as having enough clips to identify the
      tumour bed and IORT site in computed-tomography (CT). The clinical target volume
      (CTV) was assessed for each patient with two different methods: the first, cc
      IORT, was considered during surgery according to the chosen collimator diameter
      and glandular thickness, while the second, cc-CT, was evaluated through computed
      tomography performed after surgery. The cc-CT CTV was obtained by contouring the
      cc-IORT on the CT section on the basis of the clips placed by the surgeon on the
      resection margins. RESULTS: In our experience, the 5-cm (50%) and the 6-cm (36%)
      diameter collimators have been the ones, used the most. The diameter of the
      collimator used did not appear to adversely affect the satisfactory aesthetic
      result. The comparison between CTVs showed that glandular breast volume contoured
      with CT (cc-CT) appeared to be three fold larger than the target identified at
      surgery and included in the area of chosen collimator (cc-IORT). CONCLUSION: The
      actual volume of breast gland irradiated with the IORT procedure appears to be
      larger than expected. This may be due to the area being prepared for IORT by
      placing tissue compactly.

PMID- 23155265
TI  - Semi-automated volumetric quantification of tumor necrosis in soft tissue sarcoma
      using contrast-enhanced MRI.
AB  - BACKGROUND: Response Evaluation Criteria in Solid Tumors (RECIST)-defined
      measurements are limited when evaluating soft tissue sarcoma (STS) response to
      therapy. Histopathological assessment of STS response requires a determination of
      necrosis following resection. A novel semi-automated technique for volumetric
      measurement of tumor necrosis, using enhanced magnetic resonance imaging (CE
      MRI), is described. PATIENTS AND METHODS: Eighteen patients with STS were treated
      with neoadjuvant therapy and then resected. CE-MRI, obtained prior to resection,
      were evaluated by two observers using semi-automated segmentation. Tumor volume
      and percent necrosis was compared with histology and RECIST measurements.
      RESULTS: The median percent necrosis, determined histologically and from CE-MRI,
      was 71.9% and 67.8%, respectively. Accuracy of these semi-automated measurements
      was confirmed, being statistically similar to those obtained at histopathological
      assessment of the resected tumor. High Intra-class correlation co-efficients
      suggest good inter-observer reproducibility. Tumor necrosis did not correlate
      with the RECIST measurements. CONCLUSION: Semi-automated determination of tumor
      volume and necrosis, using CE-MRI, is suggested to be accurate and reproducible.

PMID- 23155267
TI  - Isolation and characterization of bone marrow-derived progenitor cells from
      malignant gliomas.
AB  - BACKGROUND: Malignant gliomas are highly-vascularised tumours. Neoangiogenesis is
      a crucial factor in the malignant behaviour of tumour and prognosis of patients.
      Several mechanisms are suspected to lead to neoangiogenesis, one of them is the
      recruitment of multipotent progenitor cells towards the tumour. Factors such as
      Vascular endothelial growth factor-A (VEGF-A) were described to recruit bone
      marrow-derived endothelial progenitor cells (EPCs) to the glioma stroma and
      vasculature. Little is known about isolating EPCs from normal or malignant
      tissues. MATERIALS AND METHODS: In this study, we addressed the topic of
      characterization of tumour-isolated EPCs and re-defined the clonal relationship
      between EPCs and hematopoietic stem cells (HSCs) in gliomas. We first checked
      public gene expression data of glioma for putative marker expression, pointing
      towards a prevalence of EPCs and HSCs in glioma. Immunohistochemical staining of
      glioma tissue confirmed the higher expression of these progenitor markers in
      glioma tissue. EPCs and HSCs were consequently isolated and characterized at the
      phenotypic and functional levels. We applied a new isolation method, for the
      first time, to specimen from patients with high grade glioma including seven
      grade IV glioblastoma, five-grade III astrocytoma, and three grade III
      oligoastrocytoma. RESULTS: In all samples, we were able to isolate the tumour
      derived EPCs, which were positive for characteristic markers: CD31, CD34 and
      VEGFR2. The EPCs formed capillary networks in vitro and had the ability to take
      up acetylated low-density lipoprotein. Glioma-derived HSCs were positive for CD34
      and CD45, but they were unable to form a capillary network in vitro. These
      findings on tumour-derived EPCs/HSCs were in concordance with the results,
      derived from peripheral blood of healthy volunteers. CONCLUSION: In our study, we
      established a new method for EPC/HSC isolation from human gliomas, defined the
      contribution of EPCs and HSCs to the tumour tissue, and highlighted the intense
      in vivo tumour host interaction.

PMID- 23155266
TI  - Uncertainty in the utility of immunohistochemistry in mismatch repair protein
      expression in epithelial ovarian cancer.
AB  - BACKGROUND: Utility of immunohistochemistry (IHC) for mismatch repair (MMR)
      protein expression has been demonstrated in colorectal cancer but remains
      incompletely defined in ovarian cancer. We evaluated MMR protein expression in
      three population-based samples of epithelial ovarian cancers. MATERIALS AND
      METHODS: IHC staining was performed on full-section (FS) or tissue microarray
      (TMA) slides for MLH1, MSH2, and MSH6 expression. RESULTS: Out of 487 cases, 147
      and 340 were performed through FS and TMA, respectively. Overall, Loss of
      Expression (LoE) of at least one MMR protein was observed in 12.7% based on an
      expression score of <=3 (on a scale of 9). Notably, LoE was significantly higher
      in TMAs (17.9%) compared to FS cases (0.7%) (p<0.001). CONCLUSION: A substantial
      proportion of epithelial ovarian cancers have a loss of MMR protein expression.
      Protein expression results vary significantly by the tissue sampling methodology
      utilized, raising concerns about the clinical utility of this test for ovarian
      tumors.

PMID- 23155268
TI  - Epistaxis secondary to panitumumab in a patient with colon cancer.
AB  - Epidermal growth factor receptor inhibitors (EGFRIs) have become an integral part
      of therapy for many types of solid malignancy, including colorectal cancer. The
      drug class has proven to be effective without causing many of the side-effects
      associated with chemotherapy or other growth factor receptor inhibitors.
      Epistaxis, a common side-effect of Vascular Endothelial Growth Factor inhibitors,
      is rarely noted with EGFRIs. We report on one patient, a 51-year-old man with
      metastatic colon cancer, who developed severe epistaxis with the use of
      panitumumab. We discuss the other reported cases of EGFRIs causing epistaxis and
      hypothesize on possible mechanisms by which this drug class might cause mucosal
      bleeding.

PMID- 23155269
TI  - Alpha-fetoprotein-producing carcinoma of the renal pelvis exhibiting hepatoid and
      urothelial differentiation.
AB  - Neoplasms commonly associated with alpha-fetoprotein (AFP) production are
      hepatocellular carcinomas and some germ cell tumors, typically yolk sac tumor.
      Rare tumors of visceral origin may also be associated with AFP production and
      those exhibiting a distinctive morphology are now known as hepatoid
      adenocarcinomas. To date, eight such tumors have been reported from the bladder
      and a further four from the renal pelvis. We report a unique case of a mixed
      hepatoid adenocarcinoma and urothelial carcinoma of the renal pelvis and ureter,
      in which both components were found to express AFP. An 84-year-old woman with a
      serum AFP level of 701 ng/ml was found to have advanced high-grade renal pelvi
      calyceal and ureteral urothelial carcinoma exhibiting focal hepatoid
      adenocarcinoma differentiation. Both components displayed strong immunostaining
      for AFP. The patient was treated by radical nephro-uretectomy and postoperatively
      the serum AFP level declined to normal at a rate commensurate with its biological
      half-life. The presence of AFP expression in both the urothelial and hepatoid
      components of the tumor suggest that the molecular pathway changes associated
      with AFP production precede the hepatoid differentiation of tumor cells.

PMID- 23155270
TI  - Effect of breast cancer adjuvant therapies on potential biomarkers of pulmonary
      inflammation.
AB  - BACKGROUND: The aim of this study was to investigate the effect of breast cancer
      adjuvant therapies on the levels of circulating surfactant protein-D (SP-D), C
      Reactive protein (CRP) and soluble receptor for advanced glycation end-products
      (sRAGE), as potential biomarkers of subclinical pulmonary inflammation. MATERIALS
      AND METHODS: The soluble molecules were serially determined in 38 patients, prior
      to the initiation of radiation therapy (RT) and during adjuvant treatment, using
      immunoassays. RESULTS: Significantly higher levels of all three biomarkers were
      observed in patients prior to the initiation of RT compared to healthy controls
      (CRP: p<0.001, SP-D: p<0.05, sRAGE: p<0.05). SP-D levels exhibited a gradual
      increase after RT and during follow-up (p<0.005). Patients treated with a
      combination of RT and hormonal therapy presented a significant, but less
      pronounced, increase in SP-D and a significant decrease in CRP compared to those
      who did not receive hormonal therapy (p=0.0428 and p=0.0116, respectively).
      Patients treated with a combination of RT and trastuzumab presented a significant
      increase in SP-D levels (p=0.0310). CONCLUSION: The average rate of change in the
      levels of circulating SP-D and CRP during postoperative irradiation and adjuvant
      hormonal therapy suggests that the combined therapeutic regiment may potentially
      exert important anti-inflammatory effects on the lung. On the contrary, combined
      administration of RT and trastuzumab is likely to induce or provoke pulmonary
      inflammation.

PMID- 23155271
TI  - Prognostic significance of ERCC1, RRM1 and BRCA1 in surgically-treated patients
      with non-small cell lung cancer.
AB  - Chemotherapy is an important modality of treatment for non-small cell lung cancer
      (NSCLC). Recent studies have shown that assessment of predictive molecular
      markers could be helpful for estimation of the response rate to chemotherapy. The
      aim of our study was to assess the relation of mRNA levels of DNA repair genes
      excision repair cross-complementary group 1 (ERCC1), ribonucleotide reductase
      subunit M1 (RRM1) and breast cancer 1 (BRCA1), in surgically-resected tumor
      tissues from patients who underwent adjuvant chemotherapy, to the disease-free
      interval (DFI) and overall survival (OS). We investigated if potential residual
      tumor cells after resection reflect properties of the primary tumor and response
      to chemotherapy according to the level of predictive markers with respect to
      current knowledge. PATIENTS AND METHODS: We studied a group of 90 patients with
      NSCLC who had undergone curative lung resection; 59 of them were subsequently
      treated with adjuvant chemotherapy, DFI and OS were evaluated only in this
      subgroup. Quantitative estimation of mRNA of selected genes in paired (tumor and
      control)-lung tissue samples was performed by real-time reverse transcription
      polymerase chain reaction (RT-PCR). RESULTS: We found a significantly lower mRNA
      expression of ERCC1 (p<0.001) and RRM1 (p=0.023) in NSCLC tumor tissues compared
      to normal lung tissues. Comparing expression in histological subtypes, we
      recorded higher mRNA expression of ERCC1 (p=0.021), RRM1 (p=0.011) and BRCA1
      (p=0.011) in adenocarcinoma than in squamous cell carcinoma (SCC). Differences in
      DFI and OS were found only in specific subgroups according to tumor type and
      stage. We found longer OS for patients with adenocarcinoma with higher expression
      of the RRM1 mRNA (p=0.002), and for patients with SCC with higher expression of
      the BRCA1 mRNA (p=0.041). In patients with NSCLC of stage III, we found longer
      DFI in those with higher expression of RRM1 (p=0.004) and ERCC1 (p=0.038).
      CONCLUSION: Patients who had been treated with adjuvant chemotherapy and had
      shown lower expression of repair genes had adverse prognosis. We observed that
      the assessment of DNA repair gene level in primary tumors treated by surgical
      resection had prognostic significance and did not predict response to adjuvant
      chemotherapy.

PMID- 23155272
TI  - Borderline serous papillary tumour of the testis: a case report and review of the
      literature.
AB  - Borderline serous tumour of the testis and paratestis is an uncommon entity. We
      report a case of borderline serous tumour of a 59-year-old male, who presented
      with a right testicular swelling which was clinically suspicious of carcinoma.
      Radical orchidectomy was performed and a cystic lesion was identified in the
      testis. Macroscopically the tumour was composed of a unilocular cyst with
      excrescences in the inner surface. The histological features were identical to
      the ovarian counterpart of borderline serous papillary tumour. The excrescences
      were formed by stratified columnar epithelium, which exhibited mild nuclear
      pleomorphism and mitotic activity, with a fibrovascular core and scattered
      psammoma bodies. There was no lymphovascular or stromal invasion. The lesion was
      surrounded by a dense fibrous wall. On immunohistochemistry, the lining
      epithelial cells expressed cytokeratin AE1/AE3 but not carcinoembryonic antigen
      or calretinin. Following the removal of the tumour, the patient was followed up
      and no recurrence or metastasis has occurred to date. This case highlights the
      need for clinicians and pathologists to be aware of this rare entity and to
      develop the best approach for patient management.

PMID- 23155273
TI  - Along the pituitary-testis-prostate axis, serum total testosterone is a
      significant preoperative variable independently contributing to separating the
      prostate cancer population into prostatectomy Gleason score groups.
AB  - AIM: To investigate, along the pituitary- testis- prostate axis, the potential of
      preoperative serum TT in contributing to defining separate prostatectomy Gleason
      score (pGS) groups of the prostate cancer (PC) population. MATERIALS AND METHODS:
      The data of 126 patients operated on for PC were retrospectively reviewed. No
      patient had previously received 5alpha-reductase inhibitor, luteinizing hormone
      (LH)-releasing hormone analogs or testosterone replacement treatment. The patient
      population was grouped according to the prostatectomy Gleason score (pGS) as
      6=3+3, 7=3+4, 7=4+3 and 8-10. Twelve variables were simultaneously investigated
      in each group: age, prolactin (PRL), follicle stimulating hormone (FSH), LH,
      total testosterone (TT), free testosterone (FT), estradiol (Er), prostate
      specific antigen (PSA), percentage of prostate biopsy positive cores (P+), biopsy
      Gleason score (bGS), overall cancer volume estimated as percentage of prostate
      volume (V+) and prostate weight (Wi). Univariate analysis of variance (ANOVA),
      multivariate analysis of variance (MANOVA) and multivariate discriminant analysis
      were the statistical methods used for evaluating the data. RESULTS: There were 38
      patients in pGS 6=3+3, 57 in pGS 7=3+4, 15 in pGS 7=4+3 and 16 in pGS 8-10. ANOVA
      showed that bGS (p<0.0001), P+ (p<0.0001), V+ (p<0.0001), PSA (p=0.02), Wi
      (p=0.001) and TT (p=0.04) were significantly different in the four pGS groups.
      MANOVA tests showed that only bGS (p<0.0001) and TT (p=0.005) were the
      significant variables that individually and independently contributed a
      significant amount to separation of the four pGS groups of the PC population.
      Multivariate discriminant analysis confirmed that TT (p=0.005) and bGS (p<0.0001)
      were the only variables that independently and significantly contributed to
      separating the pGS groups. CONCLUSION: along the pituitary- testis- prostate
      axis, serum TT is a significant preoperative variable that independently
      contributes to separating the prostate cancer population into pGS score groups.
      Pretreatment baseline serum TT levels should be measured for their inclusion in
      nomograms and future neural networks to be considered in the patient population
      diagnosed with PC.

PMID- 23155274
TI  - Radical nephrectomy with transperitoneal subcostal incision for large and locally
      advanced tumors of the right kidney.
AB  - BACKGROUND: Several surgical approaches have been used for radical nephrectomy
      for large and locally advanced tumors of the right kidney. AIM: To present our
      experience with radical nephrectomy using a right subcostal incision with a
      transperitoneal approach in patients with very large tumors of the right kidney.
      PATIENTS AND METHODS: Between 2003 and 2010, 34 patients with very large tumors
      of the right kidney were submitted to surgery. Eighteen patients underwent a
      transperitoneal approach with a right subcostal incision (intervention group) and
      16 patients were operated on with retroperitoneal flank incision (control group).
      RESULTS: No significant complications during surgery were observed in the
      intervention group; two patients needed blood transfusions of 300 cc during the
      first postoperative day. In the control group, injury of the renal vein or
      inferior vena cava (IVC) was a relatively common complication; five patients
      needed blood transfusions of 300 cc during the first postoperative day.
      CONCLUSION: A transperitoneal right subcostal incision for radical nephrectomy in
      patients with large and locally advanced tumors of the right kidney seems to
      offer better access to the renal pedicle, and to the great vessels of the area as
      well as better exposure of the organs of the abdominal cavity. This approach
      could be more useful in cases in which liver involvement is possible.

PMID- 23155275
TI  - c-MYC amplification in mucinous gastric carcinoma: a possible genetic alteration
      leading to deeply invasive tumors.
AB  - BACKGROUND: Patients with mucinous gastric carcinoma (MGC) usually have a poor
      prognosis, largely due to the advanced stage of disease. In this study, we
      evaluated the effects of c-MYC amplification on tumor stage and disease-specific
      survival of 128 patients with MGC and compared the results with those of 302
      patients with non-mucinous gastric carcinoma (non-MGC). PATIENTS AND METHODS: Two
      color fluorescence in situ hybridization (FISH) for c-MYC was performed on 430 GC
      samples. Real-time quantitative polymerase chain reaction (q-PCR) analysis for c
      MYC was also performed after tumor microdissection. RESULTS: c-MYC amplification
      was found in 10.2% of MGCs and 6.0% of non-MGCs. c-MYC amplification was more
      frequently found in MGCs of higher tumor stage than in MGCs of lower stage
      (p=0.038). c-MYC amplification in MGC was correlated with greater invasion depth
      (p=0.007). The mean survival time of patients with c-MYC amplification was
      shorter than that of patients without c-MYC amplification in MGC. Real-time q-PCR
      results showed that the calculated c-MYC/GAPDH ratios were higher in c-MYC
      amplified MGC than in c-MYC-non-amplified MGC. CONCLUSION: This study showed that
      c-MYC amplification in MGC is highly correlated with advanced stage and deeply
      invasive MGC. This suggests that c-MYC amplification in MGC could be a possible
      genetic alteration contributing to the frequent presentation of advanced-stage
      MGC.

PMID- 23155276
TI  - Initial safety and outcomes of miriplatin plus low-dose epirubicin for
      transarterial chemoembolisation of hepatocellular carcinoma.
AB  - AIM: To evaluate the initial safety and efficacy of combination therapy using
      miriplatin plus low-dose epirubicin for transarterial chemoembolisation (TACE) of
      unresectable hepatocellular carcinoma (HCC). PATIENTS AND METHODS: Patients who
      underwent TACE using miriplatin plus epirubicin (n=48) and control patients who
      underwent TACE using miriplatin-alone (n=51) were included in this study.
      RESULTS: The objective response rate in the miriplatin plus epirubicin group
      (91%) was significantly higher than that in the miriplatin group (74%, p=0.024).
      Concomitant use of miriplatin and epirubicin was an independent factor associated
      with higher objective response rate (hazard ratio=0.18; p=0.012). Overall
      incidence adverse events was not significantly different between the miriplatin
      plus epirubicin group (50%) and the miriplatin group (49%, p=0.575). CONCLUSION:
      TACE using miriplatin plus low-dose epirubicin was associated with an increased
      objective response rate and comparable adverse effects compared to TACE using
      miriplatin-alone.

PMID- 23155277
TI  - Quality of life and sexuality of patients after treatment for gynaecological
      malignancies: results of a prospective study in 55 patients.
AB  - AIM: To assess the sexuality and quality of life (QoL) of women with
      gynaecological malignancies after multimodal therapy. MATERIALS AND METHODS: This
      is a prospective analysis of the sexual status among women after treatment for
      gynaecological malignancies. Validated questionnaires-female sexual function
      index (FSFI-d), a semi-structured questionnaire and the quality of life score
      SF12, were applied. RESULTS: Overall, 55 patients (median age=61, range=22-74
      years) were enrolled. The cancer diagnoses were 54% ovarian, 26% breast, 13%
      cervical, 6% vulvar and 2% endometrial cancer. Twenty patients (55.6%) claimed
      experiencing changes in their sexuality after cancer treatment. The main reasons
      for this impairment were distorsion of their self image (45%; n=9), dry vaginal
      mucosa (25%; n=5), fear of physical harm (20%; n=4) and pain during sexual
      intercourse (20%; n=4). Forty percent of the patients gave no information about
      their sexuality after cancer therapy. Patients with cervical, endometrial or
      vulvar cancer had significantly higher changes in their sexuality compared to
      patients with ovarian cancer even after adjusting for age, recurrence rate and
      partnership status. The evaluation of SF12 revealed significantly higher
      psychological functional scores with increasing age. Patients who reported
      changes of their sexuality were also shown to have a lower overall SF12 score.
      CONCLUSION: Evaluation of sexuality and self image perception after cancer
      treatment is an unmet need and needs to be addressed in women with gynaecological
      malignancies. Further studies are warranted to assess the influence of the
      various types of cancer therapies in regard to their effect on sexuality and
      quality of life.

PMID- 23155278
TI  - Early relapse is associated with high serum soluble interleukin-2 receptor after
      the sixth cycle of R-CHOP chemotherapy in patients with advanced diffuse large B
      cell lymphoma.
AB  - The clinical significance of serum soluble interleukin-2 receptor (sIL2R) levels
      was retrospectively assessed in patients with advanced diffuse large B-cell
      lymphoma (DLBCL). Twenty-one patients, who were newly-diagnosed with advanced
      DLBCL (stage III and IV) between 2006 and 2009, were evaluated. The median follow
      up period was 37 months. All patients received 6-8 cycles of chemotherapy with
      rituximab in combination with doxorubicin, cyclophosphamide, vincristine, and
      prednisolone (CHOP)-like regimens and attained complete remission. Although all
      patients reached complete remission, six patients experienced disease relapse
      within 1 year after treatment completion. The overall survival was significantly
      poorer in patients with relapse than in patients with durable remission. The
      sIL2R levels after the sixth cycle of treatment were significantly higher in the
      relapse group than in the non-relapse group. Thus, the present study suggests
      sIL2R levels to be a valuable predictor for the prognosis of patients with
      advanced DLBCL.

PMID- 23155279
TI  - Percutaneous radiofrequency ablation therapy for recurrent hepatocellular
      carcinoma.
AB  - AIM: To compare the overall survival (OS) in patients without recurrent
      hepatocellular carcinoma (HCC) after initial radiofrequency ablation (RFA) and in
      those with recurrence, treated with repeat-RFA. PATIENTS AND METHODS: We compared
      OS between patients without recurrence (group A; n=150) and those with recurrence
      treated with repeat-RFA (group B; n=130). RESULTS: One-, 3- and 5-year OS after
      initial RFA was 92.6%, 84.1% and 81.0%, respectively, in group A, and 99.0%,
      84.1% and 61.8% in group B (p=0.296). There was no significant difference in OS
      between group A patients and patients with a single recurrent HCC (p=0.834). On
      multivariate analysis, serum albumin >3.5 g/dl and first HCC recurrence,
      comprising of two or three nodules were significant predicting factors of poorer
      OS. CONCLUSION: Even if HCC recurs after initial RFA, survival comparable to that
      of patients without recurrence can be achieved in patients with a single
      recurrent tumor treated with repeat-RFA.

PMID- 23155280
TI  - Metronomic cyclophosphamide with cisplatin and bevacizumab: a new
      chemotherapeutic regimen for refractory anaplastic ependymoma.
AB  - Anaplastic ependymoma is a rare brain tumor, induced both in the brain and the
      spine. The treatment relies on surgery and radiotherapy. Upon failure of these
      treatments, chemotherapy has modest effects. Here, we report two cases of
      anaplastic ependymoma with prolonged radiological and clinical responses to a
      metronomic cyclophosphamide, cisplatin and bevacizumab regimen. Two patients with
      anaplastic ependymoma, refractory to surgery and radiotherapy were proposed for a
      chemotherapeutic treatment. These patients had both spina and brain nodules.
      Neurological symptoms included arm deficiencies and paraparesia. RESULTS: Six
      cycles of the metronomic cyclophosphamide (50 mg per day, daily), cisplatin (100
      mg/m(2) every four weeks) and bevacizumab (10 mg/kg every two weeks), as a
      chemotherapeutic regimen, induced both radiological response on magnetic
      resonance imaging and clinical response with neurological deficiency regression.
      At one year, the patients were still under maintenance therapy with metronomic
      cyclophosphamide and cisplatin. This treatment still continues to control tumor
      progression and symptoms. CONCLUSION: This is the first report showing an
      impressive efficacy of metronomic the cyclophosphamide, cisplatin and bevacizumab
      chemotherapeutic regimen for the treatment of refractory anaplastic ependymoma.

PMID- 23155281
TI  - Talc pleurodesis as surgical palliation of patients with malignant pleural
      effusion. Analysis of factors affecting survival.
AB  - Malignant pleural effusion (MPE) is common in most patients with advanced cancer,
      especially in those with lung cancer, metastatic breast carcinoma and lymphoma.
      This complication usually leads patients to suffer from significant dyspnea,
      which may impair their mobility and reduce their quality of life. In patients
      with MPE, several interventions have been shown to be useful for palliation of
      the symptoms, including talc pleurodesis. The aim of this study was to evaluate
      prognostic factors for survival of patients with symptomatic MPE who underwent
      palliative video-assisted thoracoscopic (VATS) talc pleurodesis. Thirty-five
      patients with MPE underwent VATS, evacuation of the pleural fluid and talc
      pleurodesis with large-particle talc. There were 22 (62.9%) males and 13 (37.1%)
      females, with an overall median age of 69 years (range 42-81 years). The main
      causes of MPE were non-small cell lung carcinoma, breast or ovarian cancer and
      malignant pleural mesothelioma. The age did not differ (p=0.88) between men
      (68.6+/-11.6 years) and women (68.0+/-8.7 years). The mean quantity of pleural
      effusion was 2005.7+/-1078.9 ml, while the overall survival was 11.2+/-8.9
      months. We did not find any relationship between survival and gender (log-rank
      test, p=0.53) or underlying malignancy associated with MPE (p=0.89, 0.48 and 0.36
      for secondary cancer, lung cancer and mesothelioma, respectively). Similarly, no
      correlation was found between survival and age of the patients (Cox's regression,
      p=0.44) or quantity of pleural effusion (p=0.88). Our results show that the
      prognosis of patients after talc pleurodesis is independent of age, gender, type
      of malignancy and amount of pleural effusion, thus, suggesting the utility of
      treating all patients with symptomatic MPE early.

PMID- 23155282
TI  - Papillary-serous adenocarcinoma of the uterine cervix during tamoxifen therapy
      after bilateral breast cancer.
AB  - BACKGROUND: Papillary-serous adenocarcinoma (PSCC) is a very rare subtype of
      cervical cancer. To our knowledge, this is the first report on PSCC of the
      uterine cervix following bilateral breast cancer. CASE REPORT: A 61-year-old
      Caucasian woman underwent conserving surgery of both breasts at the age of 57
      years, because of bilateral invasive ductal carcinoma. Radiation and tamoxifen
      treatment followed. Routine surveillance examinations, including pelvic
      examination, Papanicolaou (Pap) smear, and transvaginal ultrasound, were
      uneventful. Recently, a small contact-bleeding mass of the cervix was found. The
      Pap smear was II (reactive); HPV-DNA test was negative. The biopsy of the mass
      revealed PSCC with a high expression of p53, carcinoembryonic antigen (CEA), and
      Ki67 (50%). Staining for estrogen receptor (ER), progesterone receptor (PR), and
      vimentin was negative. The serum carbohydrate antigen 125 (CA-125) reached 159
      U/ml. The patient was treated with radical hysterectomy, bilateral salpingo
      oophorectomy, and pelvic and paraaortic lymphadenectomy. A poorly-differentiated
      papillary-serous, non-secretory adenocarcinoma, pT1b1, pN0 (0/44), pM0, G3, R0,
      V0, L0, was confirmed. According to the German recommendations for early-stage
      cervical cancer, the patient received no adjuvant treatment. Currently, the
      patient is free of relapse 38 months after the diagnosis of cervical cancer and
      87 months after that of breast cancer. CONCLUSION: Immunohistochemistry is
      helpful in diagnosing rare entities. This case adds further evidence that the
      prognosis for early-stage PSCC is probably not poorer than that for other
      cervical adenocarcinomas.

PMID- 23155283
TI  - Neuroendocrine carcinoma of the breast--diagnostic and clinical implications.
AB  - BACKGROUND: Neuroendocrine breast carcinomas (NEC) are rare. Carcinomas with
      mixed composition often behave differently from 'pure' histological types, and
      the prognosis is determined by the proportion of the more aggressive tumour. The
      molecular classification helps in making therapeutic decisions. CASE REPORT: A 56
      year-old Caucasian woman with palpable and preoperatively biopsied breast tumour
      was treated with breast-conserving surgery. The histological specimen revealed a
      17-mm invasive carcinoma with an equal proportion of neuroendocrine and invasive
      ductal differentiation, accompanied by peritumoural ductal carcinoma in situ. TNM
      classification was pT1c(is), pN0 (0/1sn), G3, L0, V0, Pn0, R0. The diagnosis was
      enhanced by immunohistochemistry: high positivity for synaptophysin, neuron
      specific enolase (NSE), neural cell adhesion molecule (CD56), Ki-67
      (proliferation index 46%), estrogen receptor (ER) and progesterone receptor (PR),
      negative for Her-2-neu and cytokeratin 5/6, resulting in diagnosis of the
      molecular 'luminal B' subtype. Radiation and adjuvant chemotherapy with six
      cycles of 5-fluorouracil, epirubicin and cyclophosphamide, followed by tamoxifen
      and subsequent exemestane for five years, were recommended. CONCLUSION:
      Immunohistochemistry plays a crucial role in the diagnosis of rare cancer
      subtypes. NEC is characterized by high biological aggressiveness. Molecular
      classification facilitates therapeutic decisions.

PMID- 23155284
TI  - Pelvic radiotherapy after renal transplantation.
AB  - BACKGROUND: After renal transplantation, patients have a higher incidence of
      developing cancer necessitating pelvic radiotherapy, but there is a lack of data
      for such therapy in this patient group. PATIENTS AND METHODS: Nine patients with
      pelvic renal transplants were treated with pelvic radiotherapy between 04/2002
      and 06/2011. Treatment was carried out for prostate (n=4), rectal (n=2), and anal
      cancer (n=1), osseous metastasis (n=1), and Hodgkin's disease (n=1). The mean age
      of the transplants was 12.6 years. RESULTS: The mean total dose to the target
      volume was 60.2 Gy, the mean maximum dose to the transplant was 10.0 Gy, with a
      mean dose of 2.1 Gy. The mean creatinine clearance before start of radiotherapy
      was 48.9 ml/min. After a mean follow-up of 23 months, no patient showed failure
      of the transplant and the mean creatinine clearance was 64.2 ml/min. CONCLUSION:
      Using modern radiotherapy techniques, low doses to the transplant can be achieved
      without compromising target treatment and without transplant failure. A mean dose
      of <4 Gy seems to be well-tolerated by the graft.

PMID- 23155285
TI  - Prognostic value of preoperative metabolic tumor volumes on PET-CT in predicting
      disease-free survival of patients with stage I non-small cell lung cancer.
AB  - BACKGROUND: This study aimed to determine the relationship between the pre
      operative metabolic tumor volume (MTV) and the disease-free survival (DFS) of
      patients with stage I non-small cell lung cancer (NSCLC) using F-18 2-fluoro-2
      deoxy-D-glucose (FDG) positron-emission tomography-computed tomography (PET-CT)
      scanning. MATERIALS AND METHODS: Data from sixty patients with stage I NSCLC who
      had undergone preoperative F-18 FDG PET-CT scanning were retrospectively
      analyzed. The early and late maximum standardized uptake values (eSUVm and lSUVm,
      respectively) were measured from attenuation-corrected F-18 FDG PET-CT images.
      Three MTV segmentation methods were applied as an isocontour at an early SUV of
      2.5 (MTV2.5) or using fixed thresholds of either 40% (MTV40%) or 50% (MTV50%) of
      the maximum intratumoral F-18 FDG activity. DFS was compared by employing the
      Kaplan-Meier method, using the median values as cutoffs for each parameter. The
      log-rank test and Cox regression were performed to explore the effect of the
      different MTV variables on DFS. Time-dependent receiver operating characteristic
      (ROC) curves were created to evaluate the predictive performance. RESULTS: During
      a median follow-up duration of 24 months, two patients died of disease
      progression, and 11 experienced recurrent tumors (eight intrathoracic tumors, two
      distant metastasis, and one both types of recurrences). The univariate analyses
      showed that pathological stage 1B, histological type of squamous cell carcinoma,
      male sex, maximum tumor size over 2 cm, eSUVm, lSUVm, and MTV2.5 were associated
      with reduced DFS. Patients who had tumors with large eSUVm or large lSUVm had a
      significantly lower 2-year DFS, compared with patients who had smaller tumors
      (65% vs. 96%, p=0.002; 63% vs. 96%, p=0.000). Patients with an MTV2.5 greater
      than 9.8 ml had a lower 2-year DFS than those with an MTV of 9.8 ml or greater
      (59 vs. 85%, p=0.02). However, multivariate analysis showed that lSUVm over 3.4
      was the only parameter that exhibited an impact on DFS (p=0.05, hazard
      ratio=10.7), and the observed influence was marginal. CONCLUSION: For patients
      with stage I NSCLC treated with surgery, preoperative MTV parameters have a
      limited prognostic value for predicting DFS.

PMID- 23155286
TI  - Nuclear matrix protein 22 for bladder cancer detection: comparative analysis of
      the BladderChek(r) and ELISA.
AB  - AIM: To compare nuclear matrix protein 22 expression by BladderChek(r) and ELISA,
      as urine-based assays for bladder cancer (BC) detection. PATIENTS AND METHODS:
      Urine samples of 100 BC patients and 100 controls were analyzed. Comparative
      statistical evaluations were based on sensitivity and specificity. RESULTS:
      Seventy-one patients had primary and 29 recurrent BC. The sensitivity of
      BladderChek(r) was significantly higher compared to ELISA in the overall cancer
      cohort and in patients with primary BC (p<0.0001 and p=0.0001, respectively).
      Both tests demonstrated significant correlation of sensitivities and tumor
      stage/grade for the overall cancer cohort and for patients with primary BC. Both
      tests had specificity values of 100% in healthy individuals. Specificity was 93%
      for BladderChek(r) and 99% for ELISA in patients with benign diseases (p=0.048).
      CONCLUSION: BladderChek(r) may be clinically more useful for BC detection. Due to
      high specificity, BladderChek(r) could be used for high-risk screening. However,
      due to its low sensitivity, BladderChek(r) cannot replace but only complement
      cystoscopy for BC detection.

PMID- 23155287
TI  - Preoperative chemoradiotherapy using cisplatin plus S-1 can induce downstaging in
      patients with locally advanced (stage III) non-small-cell lung cancer.
AB  - BACKGROUND: About 30% of patients with non-small cell lung cancer (NSCLC) have
      locally advanced cancer (stage IIIA or IIIB) at the time of presentation. Many
      institutions have reported treatment with preoperative chemoradiotherapy (PCRT)
      followed by curative resection in patients with stage III NSCLC, but the optimal
      therapeutic protocol for this group has not been established. PATIENTS AND
      METHODS: Nineteen patients with stage III NSCLC were treated with PCRT, followed
      by surgery at the Hamanomachi Hospital, Fukuoka, Japan from May 2000 to November
      2011. We evaluated the effectiveness of PCRT for inducing downstaging using
      mainly three chemoradiotherapy regimens; cisplatin plus Tegafur-Gimeracil
      Oteracil Potassium (S-1), cisplatin plus Tegafur-Uracil (UFT), or
      1,1'cyclobutanedicarboxylate (Carboplatin, CBDCA) plus paclitaxel, with
      concurrent radiation therapy in 19 patients with stage III NSCLC. RESULTS: The
      overall 5-year survival rate was 57.1%, which is higher than the average survival
      rate for patients with stage III NSCLC in Japan. Among the regimens used, only
      cisplatin plus S-1 with concurrent radiation therapy significantly induced
      downstaging. There was a significant difference in survival time between the
      downstaged and non-downstaged groups. However, there was no significant
      difference in survival time between the S-1 plus cisplatin group and the other
      groups combined, because of the short observation period for the S-1 plus
      cisplatin group. CONCLUSION: PCRT using cisplatin plus S-1 with concurrent
      radiation therapy is useful for inducing downstaging in patients with locally
      advanced stage III NSCLC.

PMID- 23155288
TI  - Feasibility of (18)F-fluorodeoxyglucose positron-emission tomography for
      preoperative evaluation of biliary tract cancer.
AB  - (18)F-Labeled fluorodeoxyglucose positron-emission tomography (FDG-PET), a
      rapidly evolving functional imaging modality, has recently been shown to be
      useful in the diagnosis and staging of various malignant tumors due to focal
      uptake of FDG-labeled glucose in malignant cell populations. However, the role of
      FDG-PET in the diagnosis and staging of biliary tract cancer is still
      controversial and has not yet been fully evaluated. The aim of this study was to
      determine the clinical importance of FDG-PET in the preoperative evaluation of
      biliary tract cancer and retrospectively clarify the characteristics of false
      negative and false-positive cases. We retrospectively analyzed data for 73
      consecutive patients diagnosed with cancer of the biliary tract and were admitted
      to the Department of Hepato-Biliary-Pancreatic Surgery at Kobe University
      Hospital for treatment, from January 2007 to August 2009. Since the sensitivity,
      specificity and positive predictive value (PPV) of FDG-PET in the diagnosis of
      bile duct carcinoma are usually relatively high, FDG-PET is considered to be a
      useful tool in diagnosing biliary tract cancer. FDG-PET also seems to be useful
      in clinical decision-making, regarding treatment strategy, including surgery. Our
      results showed that FDG-PET is highly sensitive in delineating the primary focus
      of biliary cancer and is a useful tool in preoperative examination. A
      disadvantage of FDG-PET is its inability to indicate small metastases and false
      positive findings of inflamed gallbladder and bile duct lesions.

PMID- 23155289
TI  - An immunoassay method for the pharmacokinetics of 5-fluorouracil in patients with
      gastric cancer administered adjuvant chemotherapy.
AB  - Conventional gas chromatography-mass spectrometry (GC-MS) was compared with a new
      immunoassay method for measuring plasma (5-FU) concentrations in adjuvant
      chemotherapy with TS-1 for patients with gastric cancer. TS-1 was administered
      orally to patients after gastrectomy. Blood samples for pharmacokinetic analysis
      were collected on the seventh day of treatment. The mean area under the time
      concentration curve (AUC)(0-8), half-life (t(1/2)), and maximum drug
      concentration (C(max)) obtained by the two methods were as follows: GC-MS, 847.9
      MUg/ml/hr, 2.76 h, and 186.6 ng/ml; and immunoassay, 1311.2 MUg/ml/hr, 3.5 h, and
      259.8 ng/ml. Significant correlations were observed for AUC(0-8) (p=0.0001),
      C(max) (p=0.0007), and changes in the 5-FU concentration in blood over time
      (p=0.018) for the two methods. Compared with the conventional GC-MS method, the
      new immunoassay method provides similar results, but is simpler and results can
      be obtained earlier. This method will be useful for monitoring the 5-FU
      concentration in serum from patients with gastric cancer receiving TS-1.

PMID- 23155290
TI  - Lysozyme is up-regulated in columnar-lined Barrett's mucosa: a possible natural
      defence mechanism against Barrett's esophagus-associated pathogenic bacteria.
AB  - BACKGROUND: Lysozyme is a natural antimicrobial enzyme that is up-regulated in
      inflammatory diseases of the gastrointestinal tract. Pathogenic microbes have
      recently been identified in the esophageal mucosa in patients with Barrett's
      esophagus (BE). Lysozyme expression was evaluated in biopsies from patients with
      BE. MATERIALS AND METHODS: Ninety-seven consecutive esophageal biopsies with
      columnar-lined Barrett's mucosa (BM) were investigated: 16 had oxyntic gland-only
      BM, 19 pyloric gland-only BM and 62, intestinal metaplasia BM. Twenty normal
      gastric biopsies and 20 normal duodenal biopsies were included as controls.
      Sections were stained with human lysozyme antiserum. RESULTS: Lysozyme was up
      regulated in the neck glands in 94% of the biopsies with oxyntic gland-only BM,
      in the pyloric gland in 79% of the biopsies with pyloric gland-only BM, and in
      goblet cells in 65% of the biopsies with intestinal metaplasia BM. Goblet cells
      with faint lysozyme expression were often found in glands overexpressing lysozyme
      in mucous secretions in the lumen. When compared to controls, lysozyme was up
      regulated in all three BM phenotypes (p<0.05). CONCLUSION: Lysozyme is up
      regulated in BM. It is therefore, believed that lysozyme's up-regulation might
      mirror a molecular mechanism of self-defence aimed to safeguard the BM against
      the hostile pathogenic microbiota present in the esophageal microenvironment in
      patients with BE.

PMID- 23155291
TI  - Prognostic factors of unresectable pancreatic cancer treated with nafamostat
      mesilate combined with gemcitabine chemotherapy.
AB  - BACKGROUND: The aim of this study was to investigate prognostic factors of
      survival for patients with unresectable pancreatic cancer treated with nafamostat
      mesilate combined with gemcitabine chemotherapy. PATIENTS AND METHODS: The study
      included 41 patients who were diagnosed with unresectable pancreatic cancer and
      eligible for our clinical study of nafamostat mesilate, combined with gemcitabine
      chemotherapy for unresectable pancreatic cancer between February 2007 and
      November 2010 at Jikei University Hospital. We retrospectively investigated the
      relation between patients' characteristics and overall survival using univariate
      and multivariate analyses. RESULTS: In univariate analysis, absence of jaundice
      (p=0.0365), presence of ascites with or without histological diagnosis of
      carcinomatosis (p=0.0042), lymphocyte count >=2,000/MUl (p=0.0088), serum C
      reactive protein >=1 mg/dl (p=0.014), serum carcinoembryonic antigen >=5 ng/ml
      (p=0.0064) and serum CA19-9 >=500 U/ml (p=0.0164) were significant predictors of
      poor overall survival. In multivariate analysis, absence of jaundice (p=0.0057),
      presence of ascites with or without histological diagnosis of carcinomatosis
      (p=0.0326), lymphocyte >=2,000/MUl (p<0.0001) and CA19-9 >=500 U/ml (p=0.0198)
      were independent predictors. CONCLUSION: Jaundice, ascites, high lymphocyte count
      and high serum CA19-9 levels are independent prognostic predictors for poor
      overall survival of patients with unresectable pancreatic cancer treated with
      nafamostat mesilate combined with gemcitabine chemotherapy.

PMID- 23155292
TI  - Testicular sclerosing Sertoli cell tumor: an additional case and review of the
      literature.
AB  - Sertoli cell tumours are very rare testicular tumours accounting for 0.4-1.5% of
      all testicular neoplasms. In the current report, we present a case of sclerosing
      Sertoli cell tumour. The histology and clinical features were compared to those
      of other Sertoli cell tumour subtypes in order to assess if the different
      subtypes really represent distinct clinical and prognostic entities. The current
      literature was also reviewed. Only 20 cases of sclerosing Sertoli cell tumours
      have been encountered. Our case, a 38-year-old man represents the 21st case.
      Distinction among Sertoli cell tumours is important not only histologically;
      sclerosing Sertoli cell tumours have a distinct clinical behaviour and prognosis,
      different from those of classic and large-cell calcifying Sertoli cell tumours.
      Pathologists and urologists should know and understand all the types of Sertoli
      cell tumours in order to be able to choose the correct therapeutical approach
      when they encounter these tumours.

PMID- 23155297
TI  - Retraction. Aberrant methylation to heparan sulfate glucosamine 3-O
      sulfotransferase 2 genes as a biomarker in colorectal cancer.

PMID- 23155293
TI  - Improved quality of life in patients with malignant pleural effusion following
      videoassisted thoracoscopic talc pleurodesis. Preliminary results.
AB  - Malignant pleural effusion (MPE) is a common, debilitating complication of
      several types of advanced malignancy, which may significantly reduce the quality
      of life of patients. There are several options to treat MPE, including
      thoracentesis, placement of a long-term indwelling pleural catheter and chemical
      pleurodesis. The best treatment is still debated, but talc remains the agent of
      choice to achieve pleurodesis. Forty-six patients (28 men and 18 women; median
      age 67 years, range 47-82 years) with MPE related to different malignancies
      underwent video-assisted thoracoscopy talc pleurodesis. There were 26 (56.5%)
      patients with non-small cell lung cancer, 8 (17.4%) with breast cancer, 7 (15.2%)
      with pleural mesothelioma and 5 (10.9%) with other malignancies. The average
      operative time was 28+/-8 minutes, and the duration of chest tube drainage was
      9.4+/-4.1 days. Side-effects were mild (temporary pain, fever for 2-3 days),
      affecting only three (12%) patients. Two patients (8%) died during
      hospitalization, due to progression of disease. Overall, pre- and postoperative
      Karnofsky performance index (KI) and Medical Research Council (MRC) dyspnea score
      were 62.1+/-12.2 vs. 71.3+/-13.2 (p=0.014), and 4.2+/-0.8 vs. 2.7+/-1.0
      (p<0.001), respectively. A significant relationship between total amount of
      preoperative pleural effusion and both KI (R=-0.54, p=0.002) and MRC (R=0.64,
      p=0.0001) was found. No correlation (p=NS, log-rank test) was found between
      preoperative KI or MRC and underlying malignancy related to MPE. In conclusion,
      thoracoscopic large-particle talc pleurodesis is a feasible and effective
      treatment for MPE, significantly improving quality of life of patients.

PMID- 23155298
TI  - The Nature-Nurture Debate is Over, and Both Sides Lost! Implications for
      Understanding Gender Differences in Religiosity.

PMID- 23155299
TI  - Early Patterns of Self-Regulation as Risk and Promotive Factors in Development: A
      Longitudinal Study from Childhood to Adulthood in a High-Risk Sample.
AB  - The present study examines two childhood markers of self-regulation, ego-control
      and ego-resiliency, as promotive factors for the development of global adjustment
      and as risk factors for the development of internalizing and externalizing
      behavior problems in a high-risk sample. Teachers and observers rated ego-control
      and ego-resiliency when participants (n = 136) were in preschool and elementary
      school. Ratings showed evidence for convergent and discriminant validity and
      stability over time. Ego-resiliency, but not ego-control, emerged as powerful
      predictor of adaptive functioning at age 19 and 26, as well as internalizing and
      externalizing problems at 16, 23, 26, and 32 years. We interpret these findings
      as evidence that flexibility and adaptability -measured with ego-resiliency- may
      reduce risk and promote successful adaptation in low-SES environments.

PMID- 23155300
TI  - Religiosity, Values, and Acculturation: A Study of Turkish, Turkish Belgian, and
      Belgian Adolescents.
AB  - We address the understudied religious dimension of acculturation in acculturating
      adolescents who combine a religious Islamic heritage with a secularized Christian
      mainstream culture. The religiosity of 197 Turkish Belgian adolescents was
      compared with that of 366 agemates in Turkey (the heritage culture) and 203 in
      Belgium (the mainstream culture) and related to cultural values, acculturation
      orientations, and ethnic identification. Belgian adolescents showed lower and
      declining religiosity with age, whereas Turkish and Turkish Belgian adolescents
      were more religious regardless of age. Acculturating adolescents reaffirmed
      religion as compared with monocultural adolescents in Turkey. Religious
      reaffirmation was related to cultural values of interdependence, heritage culture
      maintenance, and ethnic identification.

PMID- 23155301
TI  - Marital Status, Gender, and Home-to-Job Conflict Among Employed Parents.
AB  - Although researchers argue that single parents perceive more work-family conflict
      than married parents, little research has examined nuances in such differences.
      Using data from the 2002 National Study of Changing Workforce (N = 1,430), this
      study examines differences in home-to-job conflict by marital status and gender
      among employed parents. Findings indicate that single mothers feel more home-to
      job conflict than single fathers, married mothers, and married fathers. Some
      predictors of home-to-job conflict vary by marital status and gender. Job
      pressure is related to home-to-job conflict more for single parents than for
      married parents. Age of children is related to conflict for single fathers only.
      Whereas an unsupportive workplace culture is related to conflict, especially for
      married fathers, the lack of spouses' share of domestic responsibilities is
      related to conflict, especially for married mothers. These findings indicate that
      marital status and gender create distinct contexts that shape employed parents'
      perceived home-to-job conflict.

PMID- 23155302
TI  - Global Self-Esteem, Appearance Satisfaction, and Self-Reported Dieting in Early
      Adolescence.
AB  - Global self-esteem, appearance satisfaction, and self-reported dieting are
      interrelated. In the current study, we examine the temporal ordering of global
      self-esteem and appearance satisfaction across the early adolescence transition,
      from age 10 to age 14, as well as the independent associations of self-esteem and
      appearance satisfaction on self-reported dieting at age 14. Participants were 130
      firstborn European American adolescents (40% girls). Adolescents who were less
      satisfied with their appearance at age 10 reported declines in self-esteem from
      age 10 to age 14. Adolescents with lower global self-esteem at age 10 did not
      decline in appearance satisfaction. Girls, adolescents with higher BMI scores at
      age 10, and adolescents who were less satisfied with their appearance at age 14
      all reported more frequent dieting at age 14. Implications for etiological and
      intervention models of eating problems in adolescence are considered.

PMID- 23155303
TI  - The role of marijuana use etiquette in avoiding targeted police enforcement.
AB  - Internationally, where marijuana is illegal, users follow etiquette rules that
      prevent negative consequences of use. In this study, adherence to etiquette is
      hypothesized to reduce likelihood of marijuana-related police stop/search and
      arrest. Ethnographers administered group surveys to a diverse, purposive sample
      of 462 marijuana-using peer groups in several areas of New York City. Findings
      indicated that lack of etiquette was associated with dramatically higher
      likelihood of police stop/search or arrest only for users who were Black, male,
      and/or recruited from Harlem/South Bronx. If these users followed a few
      identified etiquette rules, their risk of police stop/search or arrest was
      comparable to that of other users. Implications are that etiquette represents an
      intentional conscientiousness about marijuana use. Groups that are specially
      targeted for anti-marijuana enforcement can remediate that heightened risk by
      following marijuana etiquette.

PMID- 23155304
TI  - Enhanced recovery programme in colorectal surgery: does one size fit all?
AB  - Enhanced recovery after surgery (ERAS) employs a multimodal perioperative care
      pathway with the aim of attenuating the stress response to surgery and
      accelerating recovery. It has been difficult to determine the relative importance
      of some of the individual components of these pathways such as epidural analgesia
      and laparoscopic colorectal surgery. Some argue that only a rigid adherence to
      the published ERAS protocol can achieve the proposed benefits of fast-track
      surgery. In this article, we explore some of the areas where the evidence base
      may be changing and ask whether a more flexible and individualised approach
      should be considered.

PMID- 23155305
TI  - Role of Smad7 in inflammatory bowel diseases.
AB  - Crohn's disease and ulcerative colitis, the major forms of inflammatory bowel
      diseases (IBD) in man, are complex diseases in which genetic and environmental
      factors interact to promote an excessive mucosal immune response directed against
      normal components of the bacterial microflora. There is also evidence that the
      pathologic process is due to defects in counter-regulatory mechanisms, such as
      those involving the immunosuppressive cytokine transforming growth factor (TGF)
      beta1. Indeed, studies in human IBD tissues and murine models of colitis have
      documented a disruption of TGF-beta1 signalling marked by a block in the
      phosphorylation of Smad3, a signalling molecule associated with the activated TGF
      beta receptor, due to up-regulation of Smad7, an intracellular inhibitor of Smad3
      phosphorylation. Knock-down of Smad7 with a specific antisense oligonucleotide
      restores TGF-beta1/Smad3 signalling, thus resulting in a marked suppression of
      inflammatory cytokine production and attenuation of murine colitis. These
      findings together with the demonstration that Smad7 antisense oligonucleotide is
      not toxic when administered in mice have paved the way for the development of a
      Smad7 antisense oligonucleotide-based pharmaceutical compound that is now ready
      to enter the clinics. In this article we review the available data supporting the
      pathogenic role of Smad7 in IBD and discuss whether and how Smad7 antisense
      therapy could help dampen the ongoing inflammation in IBD.

PMID- 23155306
TI  - Levofloxacin/amoxicillin-based schemes vs quadruple therapy for Helicobacter
      pylori eradication in second-line.
AB  - Worldwide prevalence of Helicobacter pylori (H. pylori) infection is
      approximately 50%, with the highest being in developing countries. We compared
      cure rates and tolerability (SE) of second-line anti-H. pylori
      levofloxacin/amoxicillin (LA)-based triple regimens vs standard quadruple therapy
      (QT). An English language literature search was performed up to October 2010. A
      meta-analysis was performed including randomized clinical trials comparing 7- or
      10-d LA with 7-d QT. In total, 10 articles and four abstracts were identified.
      Overall eradication rate in LA was 76.5% (95% CI: 64.4%-97.6%). When only 7-d
      regimens were included, cure rate was 70.6% (95% CI: 40.2%-99.1%), whereas for 10
      d combinations, cure rate was significantly higher (88.7%; 95% CI: 56.1%-109.9%;
      P < 0.05). Main eradication rate for QT was 67.4% (95% CI: 49.7%-67.9%). The 7-d
      LA and QT showed comparable efficacy [odds ratio (OR): 1.09; 95% CI: 0.63-1.87],
      whereas the 10-d LA regimen was significantly more effective than QT (OR: 5.05;
      95% CI: 2.74-9.31; P < 0.001; I(2) = 75%). No differences were reported in QT
      eradication rates among Asian and European studies, whereas LA regimens were more
      effective in European populations (78.3% vs 67.7%; P = 0.05). Incidence of SE was
      lower in LA therapy than QT (OR: 0.39; 95% CI: 0.18-0.85; P = 0.02). A higher
      rate of side effects was reported in Asian patients who received QT. Our findings
      support the use of 10-d LA as a simple second-line treatment for H. pylori
      eradication with an excellent eradication rate and tolerability. The optimal
      second-line alternative scheme might differ among countries depending on
      quinolone resistance.

PMID- 23155307
TI  - Multimodality approach for locally advanced esophageal cancer.
AB  - Carcinoma of the esophagus is an aggressive and lethal malignancy with an
      increasing incidence worldwide. Incidence rates vary internationally, with the
      highest rates found in Southern and Eastern Africa and Eastern Asia, and the
      lowest in Western and Middle Africa and Central America. Patients with locally
      advanced disease face a poor prognosis, with 5-year survival rates ranging from
      15%-34%. Recent clinical trials have evaluated different strategies for
      management of locoregional cancer; however, because of stage migration and
      changes in disease epidemiology, applying these trials to clinical practice has
      become a daunting task. We searched Medline and conference abstracts for
      randomized studies published in the last 3 decades. We restricted our search to
      articles published in English. Neoadjuvant chemoradiotherapy followed by surgical
      resection is an accepted standard of care in the United States. Esophagectomy
      remains an essential component of treatment and can lead to improved overall
      survival, especially when performed at high volume institutions. The role of
      adjuvant chemotherapy following curative resection is still unclear. External
      beam radiation therapy alone is considered palliative and is typically reserved
      for patients with a poor performance status.

PMID- 23155308
TI  - Regulatory T cells in inflammatory bowel diseases and colorectal cancer.
AB  - Regulatory T cells (T(regs)) are key elements in immunological self-tolerance.
      The number of T(regs) may alter in both peripheral blood and in colonic mucosa
      during pathological circumstances. The local cellular, microbiological and
      cytokine milieu affect immunophenotype and function of T(regs). Forkhead box P3+
      T(regs) function shows altered properties in inflammatory bowel diseases (IBDs).
      This alteration of T(regs) function can furthermore be observed between Crohn's
      disease and ulcerative colitis, which may have both clinical and therapeutical
      consequences. Chronic mucosal inflammation may also influence T(regs) function,
      which together with the intestinal bacterial flora seem to have a supporting role
      in colitis-associated colorectal carcinogenesis. T(regs) have a crucial role in
      the immunoevasion of cancer cells in sporadic colorectal cancer. Furthermore,
      their number and phenotype correlate closely with the clinical outcome of the
      disease, even if their contribution to carcinogenesis has previously been
      controversial. Despite knowledge of the clinical relationship between IBD and
      colitis-associated colon cancer, and the growing number of immunological aspects
      encompassing sporadic colorectal carcinogenesis, the molecular and cellular links
      amongst T(regs), regulation of the inflammation, and cancer development are still
      not well understood. In this paper, we aimed to review the current data
      surrounding the role of T(regs) in the pathogenesis of IBD, colitis-associated
      colon cancer and sporadic colorectal cancer.

PMID- 23155309
TI  - Incidence of port-site metastasis after undergoing robotic surgery for biliary
      malignancies.
AB  - AIM: To investigate the incidence of clinically detected port-site metastasis
      (PSM) in patients who underwent robotic surgery for biliary malignancies.
      METHODS: Using a prospective database, the patients undergoing fully robotic
      surgery for biliary malignancies between January 2009 and January 2011 were
      included. Records of patients with confirmed malignancy were reviewed for
      clinicopathological data and information about PSM. RESULTS: Sixty-four patients
      with biliary tract cancers underwent robotic surgery, and sixty patients met the
      inclusion criteria. The median age was 67 year (range: 40-85 year). During a
      median 15-mo follow-up period, two female patients were detected solitary PSM
      after robotic surgery. The incidence of PSM was 3.3%. Patient 1 underwent robotic
      anatomatic left hemihepatectomy and extraction of biliary tumor thrombi for an
      Klatskin tumor. She had a subcutaneous mass located at the right lateral
      abdominal wall near a trocar scar. Patient 2 underwent robotic
      pancreaticoduodenectomy for distal biliary cancer. She had two metachronous
      subcutaneous mass situated at the right lateral abdominal wall under a same
      trocar scar at 7 and 26 mo. The pathology of the excised PSM masses confirmed
      metastatic biliary adenocarcinoma. CONCLUSION: The incidence of PSMs after
      robotic surgery for biliary malignancies is relatively low, and biliary cancer
      can be an indication of robotic surgery.

PMID- 23155310
TI  - Traditional Chinese surgical treatment for anal fistulae with secondary tracks
      and abscess.
AB  - AIM: To evaluate the efficacy and safety of traditional Chinese surgical
      treatment for anal fistulae with secondary tracks and abscess. METHODS: Sixty
      patients with intersphincteric or transsphincteric anal fistulas with secondary
      tracks and abscess were randomly divided into study group [suture dragging
      combined with pad compression (SDPC)] and control group [fistulotomy (FSLT)]. In
      the SDPC group, the internal opening was excised and incisions at external
      openings were made for drainage. Silk sutures were put through every two
      incisions and knotted in loose state. The suture dragging process started from
      the first day after surgery and the pad compression process started when all
      sutures were removed as wound tissue became fresh and without discharge. In the
      FSLT group, the internal opening and all tracts were laid open and cleaned by
      normal saline postoperatively till all wounds healed. The time of healing,
      postoperative pain score (visual analogue scale), recurrence rate, patient
      satisfaction, incontinence evaluation and anorectal manometry before and after
      the treatment were examined. RESULTS: There were no significant differences
      between the two groups regarding age, gender and fistulae type. The time of
      healing was significantly shorter (24.33 d in SDPC vs 31.57 d in FSLT, P < 0.01)
      and the patient satisfaction score at 1 mo postoperative follow-up was
      significantly higher in the SDPC group (4.07 in SDPC vs 3.37 in FSLT, P < 0.05).
      The mean maximal postoperative pain scores were 5.83 +/- 2.5 in SDPC vs 6.37 +/-
      2.33 in FSLT and the recurrence rates were 3.33 in SDPC vs 0 in FSLT. None of the
      patients in the two groups experienced liquid and solid fecal incontinence and
      lifestyle alteration postoperatively. The Wexner score after treatment of
      intersphincter fistulae were 0.17 +/- 0.41 in SDPC vs 0.40 +/- 0.89 in FSLT and
      trans-sphincter fistulae were 0.13 +/- 0.45 in SDPC vs 0.56 +/- 1.35 in FSLT. The
      maximal squeeze pressure and resting pressure declined after treatment in both
      groups. The maximal anal squeeze pressures after treatment were reduced (23.17 +/
      3.73 Kpa in SDPC vs 22.74 +/- 4.47 Kpa in FSLT) and so did the resting pressures
      (12.36 +/- 2.15 Kpa in SDPC vs 11.71 +/- 1.87 Kpa in FSLT), but there were
      neither significant differences between the two groups and nor significant
      differences before or after treatment. CONCLUSION: Traditional Chinese surgical
      treatment SDPC for anal fistulae with secondary tracks and abscess is safe,
      effective and less invasive.

PMID- 23155311
TI  - Ethyl pyruvate protects against experimental acute-on-chronic liver failure in
      rats.
AB  - AIM: To investigate the protective effects of ethyl pyruvate (EP) on acute-on
      chronic liver failure (ACLF) in rats. METHODS: An ACLF model was established in
      rats, and animals were randomly divided into normal, model and EP treatment
      groups. The rats in EP treatment group received EP (40 mg/kg) at 3 h, 6 h, 12 h
      and 24 h after induction of ACLF. Serum endotoxin, high mobility group box-1
      (HMGB1), alanine transaminase (ALT), tumor necrosis factor-alpha (TNF-alpha),
      interferon-alpha (IFN-gamma), interleukin (IL)-10 and IL-18 levels, changes of
      liver histology and HMGB1 expressions in liver tissues were detected at 48 h
      after induction of ACLF. The effects of EP on the survival of ACLF rats were also
      observed. RESULTS: Serum levels of endotoxin (0.394 +/- 0.066 EU/mL vs 0.086 +/-
      0.017 EU/mL, P < 0.001), HMGB1 (35.42 +/- 10.86 MUg/L vs 2.14 +/- 0.27 MUg/L, P <
      0.001), ALT (8415.87 +/- 3567.54 IU/L vs 38.64 +/- 8.82 IU/L, P < 0.001), TNF
      alpha (190.77 +/- 12.34 ng/L vs 124.40 +/- 4.12 ng/L, P < 0.001), IFN-gamma
      (715.38 +/- 86.03 ng/L vs 398.66 +/- 32.91 ng/L, P < 0.001), IL-10 (6.85 +/- 0.64
      ng/L vs 3.49 +/- 0.24 ng/L, P < 0.001) and IL-18 (85.19 +/- 3.49 ng/L vs 55.38 +/
      1.25 ng/L, P < 0.001) were significantly increased, and liver tissues presented
      severe pathological injury in the model group compared with the normal group.
      However, EP administration significantly improved hepatic histopathology and
      reduced the serum levels of endotoxin (0.155 +/- 0.045 EU/mL vs 0.394 +/- 0.066
      EU/mL, P < 0.001) and inflammatory cytokines (11.13 +/- 2.58 MUg/L vs 35.42 +/-
      10.86 MUg/L for HMGB1, 3512.86 +/- 972.67 IU/L vs 8415.87 +/- 3567.54 IU/L for
      ALT, 128.55 +/- 5.76 ng/L vs 190.77 +/- 12.34 ng/L for TNF-alpha, 438.16 +/-
      38.10 ng/L vs 715.38 +/- 86.03 ng/L for IFN-gamma, 3.55 +/- 0.36 ng/L vs 6.85 +/-
      0.64 ng/L for IL-10, and 60.35 +/- 1.63 ng/L vs 85.19 +/- 3.49 ng/L for IL-18,
      respectively, P < 0.001), and the levels of HMGB1 in liver tissues regardless of
      treatment time after induction of ACLF. EP treatment at the four time points
      prolonged the median survival time of ACLF rats (60 h) to 162 h, 120 h, 102 h and
      78 h, respectively (chi(2) = 41.17, P < 0.0001). CONCLUSION: EP administration
      can protect against ACLF in rats, and is a potential and novel therapeutic agent
      for severe liver injury.

PMID- 23155312
TI  - Exogenous carbon monoxide attenuates inflammatory responses in the small
      intestine of septic mice.
AB  - AIM: To determine whether the carbon monoxide (CO)-releasing molecules (CORM)
      liberated CO suppress inflammatory responses in the small intestine of septic
      mice. METHODS: The C57BL/6 mice (male, n = 36; weight 20 +/- 2 g) were assigned
      to four groups in three respective experiments. Sepsis in mice was induced by
      cecal ligation and puncture (CLP) (24 h). Tricarbonyldichlororuthenium (II) dimer
      (CORM-2) (8 mg/kg, i.v.) was administrated immediately after induction of CLP.
      The levels of inflammatory cytokines [interleukin-1beta (IL-1beta) and tumor
      necrosis factor-alpha (TNF-alpha)] in tissue homogenates were measured with
      enzyme-linked immunosorbent assay. The levels of malondialdehyde (MDA) in the
      tissues were determined. The levels of nitric oxide (NO) in tissue homogenate
      were measured and the expression levels of intercellular adhesion molecule 1
      (ICAM-1) and inducible nitric oxide synthase (iNOS) in the small intestine were
      also assessed. NO and IL-8 levels in the supernatants were determined after the
      human adenocarcinoma cell line Caco-2 was stimulated by lipopolysaccharide (LPS)
      (10 g/mL) for 4 h in vitro. RESULTS: At 24 h after CLP, histological analysis
      showed that the ileum and jejunum from CLP mice induced severe edema and
      sloughing of the villous tips, as well as infiltration of inflammatory cells into
      the mucosa. Semi-quantitative analysis of histological samples of ileum and
      jejunum showed that granulocyte infiltration in the septic mice was significantly
      increased compared to that in the sham group. Administration of CORM-2
      significantly decreased granulocyte infiltration. At 24 h after CLP, the tissue
      MDA levels in the mid-ileum and mid-jejunum significantly increased compared to
      the sham animals (103.68 +/- 23.88 nmol/mL vs 39.66 +/- 8.23 nmol/mL, 89.66 +/-
      9.98 nmol/mL vs 32.32 +/- 7.43 nmol/mL, P < 0.01). In vitro administration of
      CORM-2, tissue MDA levels were significantly decreased (50.65 +/- 11.46 nmol/mL,
      59.32 +/- 6.62 nmol/mL, P < 0.05). Meanwhile, the tissue IL-1beta and TNF-alpha
      levels in the mid-ileum significantly increased compared to the sham animals
      (6.66 +/- 1.09 pg/mL vs 1.67 +/- 0.45 pg/mL, 19.34 +/- 3.99 pg/mL vs 3.98 +/-
      0.87 pg/mL, P < 0.01). In vitro administration of CORM-2, tissue IL-1beta and TNF
      alpha levels were significantly decreased (3.87 +/- 1.08 pg/mL, 10.45 +/- 2.48
      pg/mL, P < 0.05). The levels of NO in mid-ileum and mid-jejunum tissue homogenate
      were also decreased (14.69 +/- 2.45 nmol/mL vs 24.36 +/- 2.97 nmol/mL, 18.47 +/-
      2.47 nmol/mL vs 27.33 +/- 3.87 nmol/mL, P < 0.05). The expression of iNOS and
      ICAM-1 in the mid-ileum of septic mice at 24 h after CLP induction significantly
      increased compared to the sham animals. In vitro administration of CORM-2,
      expression of iNOS and ICAM-1 were significantly decreased. In parallel, the
      levels of NO and IL-8 in the supernatants of Caco-2 stimulated by LPS was
      markedly decreased in CORM-2-treated Caco-2 cells (2.22 +/- 0.12 nmol/mL vs 6.25
      +/- 1.69 nmol/mL, 24.97 +/- 3.01 pg/mL vs 49.45 +/- 5.11 pg/mL, P < 0.05).
      CONCLUSION: CORM-released CO attenuates the inflammatory cytokine production (IL
      1beta and TNF-alpha), and suppress the oxidative stress in the small intestine
      during sepsis by interfering with protein expression of ICAM-1 and iNOS.

PMID- 23155313
TI  - Intramuscular vs intradermal route for hepatitis B booster vaccine in celiac
      children.
AB  - AIM: To compare intradermal (ID) and intramuscular (IM) booster doses, which have
      been used in healthy and high risk subjects, such as healthcare workers,
      haemodialysis patients, human immunodeficiency virus patients, and renal
      transplant recipients unresponsive to initial hepatitis B vaccination, in celiac
      individuals. METHODS: We conducted our study on 58 celiac patients, vaccinated in
      the first year of life, whose blood analysis had showed the absence of protective
      hepatitis B virus (HBV) antibodies. All patients had received the last vaccine
      injection at least one year before study enrolment and they had been on a gluten
      free diet for at least 1 year. In all patients we randomly performed an HBV
      vaccine booster dose by ID or IM route. Thirty celiac patients were revaccinated
      with recombinant hepatitis B vaccine (Engerix B) 2 MUg by the ID route, while 28
      celiac patients were revaccinated with Engerix B 10 MUg by the IM route. Four
      weeks after every booster dose, the anti-hepatitis B surface (HBs) antibody titer
      was measured by an enzyme-linked immune-adsorbent assay. We performed a maximum
      of three booster doses in patients with no anti-HBs antibodies after the first or
      the second vaccine dose. The cut off value for a negative anti-HBs antibody titer
      was 10 IU/L. Patients with values between 10 and 100 IU/L were considered "low
      responders" while patients with an antibody titer higher than 1000 IU/L were
      considered "high responders". RESULTS: No significant difference in age, gender,
      duration of illness, and years of gluten intake was found between the two groups.
      We found a high percentage of "responders" after the first booster dose (ID =
      76.7%, IM = 78.6%) and a greater increase after the third dose (ID = 90%, IM =
      96.4%) of vaccine in both groups. Moreover we found a significantly higher number
      of high responders (with an anti-HBs antibody titer > 1000 IU/L) in the ID (40%)
      than in the IM (7.1%) group, and this difference was evident after the first
      booster dose of vaccination (P < 0.01). No side effects were recorded in
      performing delivery of the vaccine by either the ID or IM route. CONCLUSION: Our
      study suggests that both ID and IM routes are effective and safe options to
      administer a booster dose of HBV vaccine in celiac patients. However the ID route
      seems to achieve a greater number of high responders and to have a better
      cost/benefit ratio.

PMID- 23155314
TI  - Prognostic factors for recurrence of gastrointestinal bleeding due to Dieulafoy's
      lesion.
AB  - AIM: To analyze the effectiveness of the endoscopic therapy and to identify
      prognostic factors for recurrent bleeding. METHODS: Retrospective study of
      patients with gastrointestinal bleeding secondary to Dieulafoy's lesion (DL) from
      2005 to 2011. We analyzed the demographic characteristics of the patients, risk
      factors for gastrointestinal bleeding, endoscopic findings, characteristics of
      the endoscopic treatment, and the recurrence of bleeding. We included cases in
      which endoscopy described a lesion compatible with Dieulafoy. We excluded
      patients who had potentially bleeding lesions such as angiodysplasia in other
      areas or had undergone other gastrointestinal endoscopic procedures. RESULTS:
      Twenty-nine patients with DL were identified. Most of them were men with an
      average age of 71.5 years. Fifty-five percent of the patients received
      antiaggregatory or anticoagulant therapy. The most common location for DL was the
      stomach (51.7%). The main type of bleeding was oozing in 65.5% of cases. In 27.6%
      of cases, there was arterial (spurting) bleeding, and 6.9% of the patients
      presented with an adherent clot. A single endoscopic treatment was applied to
      nine patients (31%); eight of them with adrenaline and one with argon, while 69%
      of the patients received combined treatment. Six patients (20.7%) presented with
      recurrent bleeding at a median of 4 d after endoscopy (interquartile range =
      97.75). Within these six patients, the new endoscopic treatment obtained a
      therapeutic success of 100%. The presence of arterial bleeding at endoscopy was
      associated with a higher recurrence rate for bleeding (50% vs 33.3% for other
      type of bleeding) [P = 0.024, odds ratio (OR) = 8.5, 95% CI = 1.13-63.87]. The
      use of combined endoscopic treatment prevented the recurrence of bleeding (10% vs
      44.4% of single treatment) (P = 0.034, OR = 0.14, 95% CI = 0.19-0.99).
      CONCLUSION: Endoscopic treatment of DL is safe and effective. Adrenaline
      monotherapy and arterial (spurting) bleeding are associated with a high rate of
      bleeding recurrence.

PMID- 23155315
TI  - Incidence of human papilloma virus in esophageal squamous cell carcinoma in
      patients from the Lublin region.
AB  - AIM: To assess the prevalence of human papilloma virus (HPV) in esophageal
      squamous cell carcinoma (ESCC) in the south-eastern region of Poland. METHODS:
      The study population consisted of 56 ESCC patients and 35 controls. The controls
      were patients referred to our department due to other non-esophageal and non
      oncological disorders with no gross or microscopic esophageal pathology as
      confirmed by endoscopy and histopathology. In the ESCC patients, samples were
      taken from normal mucosa (56 mucosa samples) and from the tumor (56 tumor
      samples). Tissue samples from the controls were taken from normal mucosa of the
      middle esophagus (35 control samples). Quantitative determination of DNA was
      carried out using a spectrophotometric method. Genomic DNA was isolated using the
      QIAamp DNA Midi Kit. HPV infection was identified following PCR amplification of
      the HPV gene sequence, using primers MY09 and MY11 complementary to the genome
      sequence of at least 33 types of HPV. The sequencing results were computationally
      analyzed using the basic local alignment search tool database. RESULTS: In tumor
      samples, HPV DNA was identified in 28 of 56 patients (50%). High risk HPV
      phenotypes (16 or/and 18) were found in 5 of 56 patients (8.9%), low risk in 19
      of 56 patients (33.9%) and other types of HPV (37, 81, 97, CP6108) in 4 of 56
      patients (7.1%). In mucosa samples, HPV DNA was isolated in 21 of 56 patients
      (37.5%). High risk HPV DNA was confirmed in 3 of 56 patients (5.3%), low risk HPV
      DNA in 12 of 56 patients (21.4%), and other types of HPV in 6 of 56 patients
      (10.7%). In control samples, HPV DNA was identified in 4 of 35 patients (11.4%)
      with no high risk HPV. The occurrence of HPV in ESCC patients was significantly
      higher than in the controls [28 of 56 (50%) vs 4 of 35 (11.4%), P < 0.001]. In
      esophageal cancer patients, both in tumor and mucosa samples, the predominant HPV
      phenotypes were low risk HPV, isolated 4 times more frequently than high risk
      phenotypes [19 of 56 (33.9%) vs 5 of 56 (8.9%), P < 0.001]. A higher prevalence
      of HPV was identified in female patients (71.4% vs 46.9%). Accordingly, the high
      risk phenotypes were isolated more frequently in female patients and this
      difference reached statistical significance [3 of 7 (42.9%) vs 2 of 49 (4.1%), P
      < 0.05]. Of the pathological characteristics, only an infiltrative pattern of
      macroscopic tumor type significantly correlated with the presence of HPV DNA in
      ESCC samples [20 of 27 (74.1%) vs 8 of 29 (27.6%) for ulcerative or protruding
      macroscopic type, P < 0.05]. The occurrence of total HPV DNA and both HPV high or
      low risk phenotypes did not significantly differ with regard to particular grades
      of cellular differentiation, phases in depth of tumor infiltration, grades of
      nodal involvement and stages of tumor progression. CONCLUSION: Low risk HPV
      phenotypes could be one of the co-activators or/and co-carcinogens in complex,
      progressive, multifactorial and multistep esophageal carcinogenesis.

PMID- 23155316
TI  - Intussusception due to inflammatory fibroid polyp: a case report and
      comprehensive literature review.
AB  - AIM: To give an overview of the literature on intussusception due to inflammatory
      fibroid polyp (IFP). METHODS: We present a new case of ileal intussusception due
      to IFP and a literature review of studies published in English language on
      intussusception due to IFP, accessed via PubMed and Google Scholar databases. For
      the search, the keywords used were: intussusception, IFP, intussusception and
      IFP, intussusception due to IFP, and IFP presenting as intussusception. The
      search covered all articles from 1976 to November 2011. RESULTS: We present a 38
      year-old woman who was admitted 10 d after experiencing abdominal pain, vomiting,
      and nausea. Ultrasonography demonstrated small bowel intussusception. An ileal
      intussusception due to a mass lesion 50 cm proximal to the ileocecal junction was
      found during laparotomy. Partial ileal resection and anastomosis were performed.
      A diagnosis of ileal IFP was made based on the immunohistochemical findings. In
      addition, a total of 56 reports concerning 85 cases of intussusception due to IFP
      meeting the aforementioned criteria was included in the literature review. The
      patients were aged 4 to 81 years (mean, 49 +/- 16.2 years); 44 were women (mean,
      51.8 +/- 14.3 years) and 41 were men (mean, 46 +/- 17.5 years). According to the
      location of the IFP, ileal intussusception was found in 63 patients, while 17 had
      jejunal, three had colonic, and two had ileojejunal intussusception. CONCLUSION:
      Although IFPs are rare and benign, surgery is the only solution in case of
      intestinal obstruction. Differential diagnosis should be made via
      immunohistochemical examination.

PMID- 23155317
TI  - Evaluation of sorafenib for hepatocellular carcinoma by contrast-enhanced
      ultrasonography: a pilot study.
AB  - AIM: To determine the usefulness of arrival time parametric imaging (AtPI) using
      contrast-enhanced ultrasonography (CEUS) with Sonazoid in evaluating early
      response to sorafenib for hepatocellular carcinoma (HCC). METHODS: Fourteen
      advanced HCC patients who received sorafenib 400/800 mg/d for at least 4 wk and
      were followed up by CEUS were enrolled in this study. CEUS was performed before
      treatment and 2 and 4 wk after treatment, and images of the target lesion in the
      arterial phase were recorded for each patient. The images were analyzed by AtPI.
      Color mapping (CM) images obtained by AtPI were compared before and after the
      treatment. In these CM images, the mean arrival time of the contrast agent in the
      region of interest from the starting point [mean time (MT)] was calculated. In
      each patient, differences between MT before and MT 2 and 4 wk after the treatment
      were compared with responses evaluated 4-8 wk after the treatment by dynamic
      computed tomography (CT), and statistical analysis was performed. Modified
      response evaluation criteria in solid tumors was used for the response
      evaluation. RESULTS: In CM images both 2 and 4 wk after the treatment, delays in
      the arrival time of the contrast agent were noted in 8 of the 14 patients. In the
      other 6 patients, no color changes were observed in the tumor, or red and/or
      yellow increase, suggesting a decrease in blood flow velocity between images 2
      and 4 wk after the treatment and those before the treatment. Dynamic CT could be
      performed 4-8 wk after the treatment in 13 of the 14 patients. Median differences
      in the MT were 1.13 s and 1.015 s, 2 and 4 wk after the treatment, respectively,
      in the 8 patients who showed stable disease (SD)/partial response (PR) on dynamic
      CT. Median differences in the MT were -0.39 s and -0.95 s, 2 and 4 wk after the
      treatment, respectively, in the 5 patients who showed progressive disease (PD).
      Differences in the median MT between SD/PR and PD groups were significant 2 and 4
      wk after the treatment with P = 0.019 and P = 0.028, respectively. CONCLUSION:
      AtPI by CEUS using Sonazoid is suggested to be useful for evaluating early
      responses to sorafenib.

PMID- 23155318
TI  - Nutritional status in relation to lifestyle in patients with compensated viral
      cirrhosis.
AB  - AIM: To assess the nourishment status and lifestyle of non-hospitalized patients
      with compensated cirrhosis by using noninvasive methods. METHODS: The subjects
      for this study consisted of 27 healthy volunteers, 59 patients with chronic viral
      hepatitis, and 74 patients with viral cirrhosis, from urban areas. We assessed
      the biochemical blood tests, anthropometric parameters, diet, lifestyle and
      physical activity of the patients. A homeostasis model assessment-insulin
      resistance (HOMA-IR) value of >= 2.5 was considered to indicate insulin
      resistance. We measured height, weight, waist circumference, arm circumference,
      triceps skin-fold thickness, and handgrip strength, and calculated body mass
      index, arm muscle circumference (AMC), and arm muscle area (AMA). We interviewed
      the subjects about their dietary habits and lifestyle using health assessment
      computer software. We surveyed daily physical activity using a pedometer.
      Univariate and multivariate logistic regression modeling were used to identify
      the relevant factors for insulin resistance. RESULTS: The rate of patients with
      HOMA-IR >= 2.5 (which was considered to indicate insulin resistance) was 14
      (35.9%) in the chronic hepatitis and 17 (37.8%) in the cirrhotic patients. AMC
      (%) (control vs chronic hepatitis, 111.9% +/- 10.5% vs 104.9% +/- 10.7%, P =
      0.021; control vs cirrhosis, 111.9% +/- 10.5% vs 102.7% +/- 10.8%, P = 0.001) and
      AMA (%) (control vs chronic hepatitis, 128.2% +/- 25.1% vs 112.2% +/- 22.9%, P =
      0.013; control vs cirrhosis, 128.2% +/- 25.1% vs 107.5% +/- 22.5%, P = 0.001) in
      patients with chronic hepatitis and liver cirrhosis were significantly lower than
      in the control subjects. Handgrip strength (%) in the cirrhosis group was
      significantly lower than in the controls (control vs cirrhosis, 92.1% +/- 16.2%
      vs 66.9% +/- 17.6%, P < 0.001). The results might reflect a decrease in muscle
      mass. The total nutrition intake and amounts of carbohydrates, protein and fat
      were not significantly different amongst the groups. Physical activity levels
      (kcal/d) (control vs cirrhosis, 210 +/- 113 kcal/d vs 125 +/- 74 kcal/d, P =
      0.001), number of steps (step/d) (control vs cirrhosis, 8070 +/- 3027 step/d vs
      5789 +/- 3368 step/d, P = 0.011), and exercise (Ex) (Ex/wk) (control vs
      cirrhosis, 12.4 +/- 9.3 Ex/wk vs 7.0 +/- 7.7 Ex/wk, P = 0.013) in the cirrhosis
      group was significantly lower than the control group. The results indicate that
      the physical activity level of the chronic hepatitis and cirrhosis groups were
      low. Univariate and multivariate logistic regression modeling suggested that Ex
      was associated with insulin resistance (odds ratio, 6.809; 95% CI, 1.288-36.001;
      P = 0.024). The results seem to point towards decreased physical activity being a
      relevant factor for insulin resistance. CONCLUSION: Non-hospitalized cirrhotic
      patients may need to maintain an adequate dietary intake and receive lifestyle
      guidance to increase their physical activity levels.

PMID- 23155319
TI  - Correlations between endoscopic and clinical disease activity indices in
      intestinal Behcet's disease.
AB  - AIM: To develop a novel endoscopic severity model of intestinal Behcet's disease
      (BD) and to evaluate its feasibility by comparing it with the actual disease
      activity index for intestinal Behcet's disease (DAIBD). METHODS: We reviewed the
      medical records of 167 intestinal BD patients between March 1986 and April 2011.
      We also investigated the endoscopic parameters including ulcer locations,
      distribution, number, depth, shape, size and margin to identify independent
      factors associated with DAIBD. An endoscopic severity model was developed using
      significant colonoscopic variables identified by multivariate regression analysis
      and its correlation with the DAIBD was evaluated. To determine factors related to
      the discrepancy between endoscopic severity and clinical activity, clinical
      characteristics and laboratory markers of the patients were analyzed. RESULTS: A
      multivariate regression analysis revealed that the number of intestinal ulcers
      (>= 2, P = 0.031) and volcanoshaped ulcers (P = 0.001) were predictive factors
      for the DAIBD. An endoscopic severity model (Y) was developed based on selected
      endoscopic variables as follows: Y = 47.44 + 9.04 * non-Ileocecal area + 11.85 *
      >= 2 of intestinal ulcers + 5.03 * shallow ulcers + 12.76 * deep ulcers + 4.47 *
      geographic-shaped ulcers + 26.93 * volcano-shaped ulcers + 8.65 * >= 20 mm of
      intestinal ulcers. However, endoscopic parameters used in the multivariate
      analysis explained only 18.9% of the DAIBD variance. Patients with severe DAIBD
      scores but with moderately predicted disease activity by the endoscopic severity
      model had more symptoms of irritable bowel syndrome (21.4% vs 4.9%, P = 0.026)
      and a lower rate of corticosteroid use (50.0% vs 75.6%, P = 0.016) than those
      with severe DAIBD scores and accurately predicted disease by the model.
      CONCLUSION: Our study showed that the number of intestinal ulcers and volcano
      shaped ulcers were predictive factors for severe DAIBD scores. However, the
      correlation between endoscopic severity and DAIBD (r = 0.434) was weak.

PMID- 23155320
TI  - Bisphosphonate use and gastrointestinal tract cancer risk: meta-analysis of
      observational studies.
AB  - AIM: To perform a meta-analysis of observational studies to further elucidate the
      relationship between oral bisphosphonate use and gastrointestinal cancer risk.
      METHODS: Systematic literature search was conducted in MEDLINE, EMBASE, and the
      Cochrane Library to identify studies through January 2011. Search terms were
      "bisphosphonates" or trade names of the drugs, and "observational studies" or
      "cohort studies" or "case-control studies". Two evaluators reviewed and selected
      articles on the basis of predetermined selection criteria as followed: (1)
      observational studies (case-control or cohort studies) on bisphosphonate use; (2)
      with at least 2 years of follow-up; and (3) reported data on the incidence of
      cancer diagnosis. The DerSimonian and Laird random effects model were used to
      calculate the pooled relative risk (RR) with 95% confidence interval (CI). Two-by
      two contingency table was used to calculate the outcomes not suitable for meta
      analysis. Subgroup meta-analyses were conducted for the type of cancer
      (esophageal, gastric and colorectal cancers). Sensitivity analyses were performed
      to examine the effect sizes when only studies with long-term follow-up (mean 5
      years; subgroup 3 years) were included. RESULTS: Of 740 screened articles, 3
      cohort studies and 3 case-control studies were included in the analyses. At
      first, 4 cohort studies and 3 case-control studies were selected for the analyses
      but one cohort study was excluded because the cancer outcomes were not
      categorized by type of gastrointestinal cancer. More than 124,686 subjects
      participated in the 3 cohort studies. The mean follow-up time in all of the
      cohort studies combined was approximately 3.88 years. The 3 case-control studies
      reported 3070 esophageal cancer cases and 15,417 controls, 2018 gastric cancer
      cases and 10,007 controls, and 11,574 colorectal cancer cases and 53,955
      controls. The percentage of study participants who used bisphosphonate was 2.8%
      among the cases and 2.9% among the controls. The meta-analysis of all the studies
      found no significant association between bisphosphonate use and gastrointestinal
      cancer. Also no statistically significant association was found in a meta
      analysis of long-term follow-up studies. There was no negative association
      between bisphosphonate use and the incidence of esophageal cancer in the overall
      analysis (RR 0.96, 95% CI: 0.65-1.42, I(2) = 52.8%, P = 0.076) and no
      statistically significant association with long-term follow-up (RR 1.74, 95% CI:
      0.97-3.10, I(2) = 58.8%, P = 0.119). No negative association was found in the
      studies reporting the risk of gastric cancer (RR 0.89, 95% CI: 0.71-1.13, I(2) =
      0.0%, P = 0.472). In case of colorectal cancer, there was no association between
      colorectal cancer and bisphosphonate use (RR 0.62, 95% CI: 0.30-1.29, I(2) =
      88.0%, P = 0.004) and also in the analysis with long-term follow-up (RR 0.61, 95%
      CI: 0.28-1.35, I(2) = 84.6%, P = 0.011). CONCLUSION: Oral bisphosphonate use had
      no significant effect on gastrointestinal cancer risk. However, this finding
      should be validated in randomized controlled trials with long-term follow-up.

PMID- 23155321
TI  - Effect of ezetimibe on the prevalence of cholelithiasis.
AB  - AIM: To investigate the prevalence of cholelithiasis among patients treated with
      ezetimibe. METHODS: A retrospective, case-control study based on computerized
      medical records from patients of the Clalit Health Services, Sharon-Shomron
      region, from 2000 to 2009. Patients 20-85 years of age, who had been treated with
      ezetimibe and statins or statins only for at least 6 mo, and who had an abdominal
      ultrasound were included in the study. Collected data included age, gender,
      ezetimibe treatment duration, presence of hypothyroidism or diabetes, and
      existence of cholelithiasis as determined by ultrasound. Excluded were subjects
      after gallbladder resection, with hemolysis, myeloproliferative or inflammatory
      bowel diseases, and those treated with ursodeoxycholic acid and fibrates.
      Patients treated with statins and ezetimibe (study group) were compared to
      patients treated with statins only (control group). RESULTS: The study group
      included 25 patients and the control group 168. All patients in the study were
      treated with statins. The study group included 13 males (52%) and 12 females
      (48%), the control group 76 males (45%) and 92 (55%) females (P = 0.544). The
      groups did not differ in age (mean age: 68 +/- 8 years, range 53-85 years vs mean
      age: 71 +/- 8 years, range 51-85 years; P = 0.153) or in the rate of diabetic and
      hypothyroid patients [11 (44%) vs 57 (33%), P = 0.347 in the study group and 5
      (20%) vs 23 (14%), P = 0.449 in the control group, respectively]. Patients in the
      study group were treated with ezetimibe for an average of 798 +/- 379 d.
      Cholelithiasis was found in 4 (16%) patients in the study group and in 33 (20%)
      patients in the control group (P = 0.666). CONCLUSION: Ezetimibe does not appear
      to influence the prevalence of gallstones.

PMID- 23155322
TI  - Treatment of chronic hepatitis delta virus with peg-interferon and factors that
      predict sustained viral response.
AB  - AIM: To observe the efficacy of peg-interferon in the treatment of hepatitis
      delta virus (HDV) and to identify the factors that would be predictive of the
      sustained viral response (SVR). METHODS: This prospective study was conducted in
      Medical Unit IV of the Liaquat University of Medical and Health Sciences Hospital
      Jamshoro from June 2008 to September 2011. This study cohort included all
      patients of either sex who presented during this time with hepatitis B surface
      antigen positivity, hepatitis B virus DNA > 20,000 IU/mL, serum glutamic pyruvic
      transaminase (SGPT) > 2(upper limit of normal), HDV-RNA positivity with fibrosis
      stage >= 2. Informed consent was obtained from each of these individuals.
      Patients were diagnosed with hepatitis D on the basis of detectable viral
      antibodies and the presence of HDV-RNA in their serum. A liver biopsy was
      performed in all cases and fibrosis staging was performed in accordance with the
      METAVIR scoring system. All eligible patients were administered peg-interferon at
      a weekly dosage of 1.5 MUg/kg body weight for 48 wk. HDV-RNA was assayed at the
      end of this treatment period and again at 24 wk later. A biochemical response was
      determined by a normalization of SGPT at the end of the treatment or during
      follow up. The end of treatment response was defined by a HDV-RNA negative
      status. A sustained virological response was defined by undetectable serum HDV
      RNA at six months after the end of treatment. RESULTS: Among the 277 patients
      enrolled in our present study, 238 completed a course of peg-interferon therapy
      of which 180 (75.6%) were male and 58 (24.4%) female. Biochemical responses were
      achieved in 122/238 (51.3%) patients. End of treatment responses were achieved in
      71/238 (29.8%) cases. A SVR was achieved in 70 of these patients (29.4%). A
      strong association was found between the SVR and the end of treatment responses
      (P = 0.001), biochemical responses (P = 0.001) and the degree of fibrosis (P =
      0.002). CONCLUSION: Peg-interferon therapy can induce remission in nearly one
      third of patients harboring HDV.

PMID- 23155323
TI  - Endoscopic submucosal dissection for foregut neuroendocrine tumors: an initial
      study.
AB  - AIM: To evaluate the feasibility and efficacy of endoscopic submucosal dissection
      (ESD) for foregut neuroendocrine tumors (NETs). METHODS: From April 2008 to
      December 2010, patients with confirmed histological diagnosis of foregut NETs
      were included. None had regional lymph node enlargement or distant metastases to
      the liver or lung on preoperative computerized tomography scanning or endoscopic
      ultrasonography (EUS). ESD was attempted under general anesthesia. After making
      several marking dots around the lesion, a mixture solution was injected into the
      submucosa. The mucosa was incised outside the marking dots. Dissection of the
      submucosal layer beneath the tumor was performed under direct vision to achieve
      complete en bloc resection of the specimen. Tumor features, clinicopathological
      characteristics, complete resection rate, and complications were evaluated.
      Foregut NETs were graded as G1, G2, or G3 on the basis of proliferative activity
      by mitotic count or Ki-67 index. All patients underwent regular follow-up to
      evaluate for any local recurrence or distant metastasis. RESULTS: Those treated
      by ESD included 24 patients with 29 foregut NETs. The locations of the 29 lesions
      are as follows: esophagus (n = 1), cardia (n = 1), stomach (n = 23), and duodenal
      bulb (n = 4). All lesions were found incidentally during routine upper
      gastrointestinal endoscopy for other indications, and none had symptoms of
      carcinoid syndrome. Preoperative EUS showed that all tumors were confined to the
      submucosa. Among the 24 gastric lesions, 16 lesions in 11 patients were type I
      gastric NETs arising in chronic atrophic gastritis with hypergastrinemia, while
      the other 8 solitary lesions were type III because of absence of atrophic
      gastritis in these cases. All of the tumors were removed in an en bloc fashion.
      The average maximum diameter of the lesions was 9.4 mm (range: 2-30 mm), and the
      procedure time was 20.3 min (range: 10-45 min). According to the World Health
      Organization 2010 classification, histological evaluation determined that 26
      lesions were NET-G1, 2 gastric lesions were NET-G2, and 1 esophageal lesion was
      neuroendocrine carcinoma (NEC). Complete resection was achieved in 28 lesions
      (28/29, 96.6%), and all of them were confined to the submucosa in histopathologic
      assessment with no lymphovascular invasion. The remaining patient with NEC
      underwent additional surgery because the resected specimens revealed
      angiolymphatic and muscularis invasion, as well as incomplete resection. Delayed
      bleeding occurred in 1 case 3 d after ESD, which was managed by endoscopic
      treatment. There were no procedure-related perforations. During a mean follow-up
      period of 24.4 mo (range: 12-48 mo), local recurrence occurred in only 1 patient
      7 mo after initial ESD. This patient successfully underwent repeat ESD.
      Metastasis to lymph nodes or distal organs was not observed in any patient. No
      patients died during the study period. CONCLUSION: ESD appears to be a safe,
      feasible, and effective procedure for providing accurate histopathological
      evaluations and curative treatment for eligible foregut NETs.

PMID- 23155324
TI  - Anorectal functional outcome after repeated transanal endoscopic microsurgery.
AB  - AIM: To evaluate the status of anorectal function after repeated transanal
      endoscopic microsurgery (TEM). METHODS: Twenty-one patients undergoing subtotal
      colectomy with ileorectal anastomosis were included. There were more than 5 large
      (> 1 cm) polyps in the remaining rectum (range: 6-20 cm from the anal edge). All
      patients, 19 with villous adenomas and 2 with low-grade adenocarcinomas,
      underwent TEM with submucosal endoscopic excision at least twice between 2005 and
      2011. Anorectal manometry and a questionnaire about incontinence were carried out
      at week 1 before operation, and at weeks 2 and 3 and 6 mo after the last
      operation. Anal resting pressure, maximum squeeze pressure, maximum tolerable
      volume (MTV) and rectoanal inhibitory reflexes (RAIR) were recorded. The
      integrity and thickness of the internal anal sphincter (IAS) and external anal
      sphincter (EAS) were also evaluated by endoanal ultrasonography. We determined
      the physical and mental health status with SF-36 score to assess the effect of
      multiple TEM on patient quality of life (QoL). RESULTS: All patients answered the
      questionnaire. Apart from negative RAIR in 4 patients, all of the anorectal
      manometric values in the 21 patients were normal before operation. Mean anal
      resting pressure decreased from 38 +/- 5 mmHg to 19 +/- 3 mmHg (38 +/- 5 mmHg vs
      19 +/- 3 mmHg, P = 0.000) and MTV from 165 +/- 19 mL to 60 +/- 11 mL (165 +/- 19
      mL vs 60 +/- 11 mL, P = 0.000) at month 3 after surgery. Anal resting pressure
      and MTV were 37 +/- 5 mmHg (38 +/- 5 mmHg vs 37 +/- 5 mmHg, P = 0.057) and 159 +/
      19 mL (165 +/- 19 mL vs 159 +/- 19 mL, P = 0.071), respectively, at month 6
      after TEM. Maximal squeeze pressure decreased from 171 +/- 19 mmHg to 62 +/- 12
      mmHg (171 +/- 19 mmHg vs 62 +/- 12 mmHg, P = 0.000) at week 2 after operation,
      and returned to normal values by postoperative month 3 (171 +/- 19 vs 166 +/- 18,
      P = 0.051). RAIR were absent in 4 patients preoperatively and in 12 (chi(2) =
      4.947, P = 0.026) patients at month 3 after surgery. RAIR was absent only in 5
      patients at postoperative month 6 (chi(2) = 0.141, P = 0.707). Endosonography
      demonstrated that IAS disruption occurred in 8 patients, and 6 patients had
      temporary incontinence to flatus that was normalized by postoperative month 3.
      IAS thickness decreased from 1.9 +/- 0.6 mm preoperatively to 1.3 +/- 0.4 mm (1.9
      +/- 0.6 mm vs 1.3 +/- 0.4 mm, P = 0.000) at postoperative month 3 and increased
      to 1.8 +/- 0.5 mm (1.9 +/- 0.6 mm vs 1.8 +/- 0.5 mm, P = 0.239) at postoperative
      month 6. EAS thickness decreased from 3.7 +/- 0.6 mm preoperatively to 3.5 +/-
      0.3 mm (3.7 +/- 0.6 mm vs 3.5 +/- 0.3 mm, P = 0.510) at month 3 and then
      increased to 3.6 +/- 0.4 mm (3.7 +/- 0.6 mm vs 3.6 +/- 0.4 mm, P = 0.123) at
      month 6 after operation. Most patients had frequent stools per day and relatively
      high Wexner scores in a short time period. While actual fecal incontinence was
      exceptional, episodes of soiling were reported by 3 patients. With regard to the
      QoL, the physical and mental health status scores (SF-36) were 56.1 and 46.2 (50
      in the general population), respectively. CONCLUSION: The anorectal function
      after repeated TEM is preserved. Multiple TEM procedures are useful for resection
      of multi-polyps in the remaining rectum.

PMID- 23155325
TI  - Treatment of recurrent sigmoid volvulus in Parkinson's disease by percutaneous
      endoscopic colostomy.
AB  - The exact aetiology of sigmoid volvulus in Parkinson's disease (PD) remains
      unclear. A multiplicity of factors may give rise to decreased gastrointestinal
      function in PD patients. Early recognition and treatment of constipation in PD
      patients may alter complications like sigmoid volvulus. Treatment of sigmoid
      volvulus in PD patients does not differ from other patients and involves
      endoscopic detorsion. If feasible, secondary sigmoidal resection should be
      performed. However, if the expected surgical morbidity and mortality is
      unacceptably high or if the patient refuses surgery, percutaneous endoscopic
      colostomy (PEC) should be considered. We describe an elderly PD patient who
      presented with sigmoid volvulus. She was treated conservatively with endoscopic
      detorsion. Surgery was consistently refused by the patient. After recurrence of
      the sigmoid volvulus a PEC was placed.

PMID- 23155326
TI  - Sarcoidosis and chronic hepatitis C: a case report.
AB  - Several case reports deal with the relationship between hepatitis C virus (HCV)
      infection and pulmonary or hepatic sarcoidosis. Most publications describe
      interferon alpha-induced sarcoidosis. However, HCV infection per se is also
      suggested to cause sarcoidosis. The present case report describes a case of
      biopsy-verified lung and liver sarcoidosis and HCV infection, and the outcome of
      antiviral therapy. In March 2009, a 25-year-old man presented with moderately
      elevated liver enzymes without any clinical symptoms. The patient was positive
      for HCV antibodies and HCV RNA of genotype 1b. Four months later the patient
      became dyspnoic and pulmonary sarcoidosis was diagnosed by lung biopsy and
      radiography. A short course of corticosteroid treatment relieved symptoms. Three
      months later, liver biopsy showed noncaseating granulomas consisting of
      epithelioid histiocytes and giant cells with a small amount of peripheral
      lymphocyte infiltration, without any signs of fibrosis. Chronic HCV infection
      with coexistence of pulmonary and hepatic sarcoidosis was diagnosed. Antiviral
      therapy with peginterferon alpha and ribavirin at standard doses was started,
      which lasted 48 wk, and sustained viral response was achieved. A second liver
      biopsy showed disappearance of granulomas and chest radiography revealed
      normalization of mediastinal and perihilar glands. The hypothesis that HCV
      infection per se may have triggered systemic sarcoidosis was proposed. Successful
      treatment of HCV infection led to continuous remission of pulmonary and hepatic
      sarcoidosis. Further studies are required to understand the relationship between
      systemic sarcoidosis and HCV infection.

PMID- 23155327
TI  - Different imaging findings of inflammatory myofibroblastic tumor of the liver.
AB  - Inflammatory myofibroblastic tumor (IMT) in the liver is an uncommon lesion of
      uncertain pathogenesis. In most cases, symptomatological imaging and clinical
      studies suggest malignancy. We report a case of liver IMT with imaging findings
      from positron emission tomography/computed tomography (PET/CT), contrast-enhanced
      computed tomography (CECT) and contrast-enhanced ultrasonography (CEUS). This
      report was the first to depict a PET/CT scan of a liver IMT that revealed an
      inhomogeneous, intense (fluorine 18)-fluoro-2-deoxy-D-glucose uptake. The CECT
      and CEUS images showed a hepatic artery supplying blood to the mass and necrosis.
      The characteristic histopathological features and the presence of spindle cells
      expressing smooth muscle actin, collagen fibers and lymphocytes allowed for the
      diagnosis of liver IMT. Recognizing such findings will help to achieve a correct
      diagnosis and may prevent inappropriate treatment.

PMID- 23155328
TI  - Midgut volvulus due to jejunal diverticula: a case report.
AB  - Jejunal diverticulosis is uncommon and often asymptomatic. It can produce
      significant complications, and some complications are potentially life
      threatening and require early surgical treatment, such as obstruction, hemorrhage
      and perforation. There is no consensus on the management of this disease. Only a
      few cases of jejunal diverticulosis with midgut volvulus have been reported. We
      herein report a case of 57-year-old woman with jejunal diverticulosis causing
      small bowel volvulus who complained of intermittent upper abdominal pin-prick for
      5 years that eventually progressed to a complete obstruction. The computed
      tomography scans revealed a mesenteric vessel "whirlpool" and laparotomy showed
      midgut volvulus secondary to jejunal diverticula. This case highlights jejunal
      diverticulosis causing small bowel volvulus as an uncommon mechanism of small
      bowel obstruction, which should be included in the differential diagnosis of
      small bowel obstruction.

PMID- 23155329
TI  - Primary squamous cell carcinoma of the liver associated with hepatolithiasis: a
      case report.
AB  - Primary squamous cell carcinoma (SCC) of the liver is rare and reported
      sporadically. Up to date, only 24 such cases have been reported in the
      literature. It is associated with hepatic teratoma, congenital cysts, solitary
      benign non-parasitic hepatic cysts, hepatolithiasis/Caroli's disease or
      cirrhosis. We reported a case of primary SCC of the liver associated with
      multiple intrahepatic cholesterol gallstones. The patient underwent hepatectomy
      followed by radiotherapy, and has survived for over 19 mo without recurrence.

PMID- 23155330
TI  - Signaling pathway/molecular targets and new targeted agents under development in
      hepatocellular carcinoma.
AB  - Advances in molecular cell biology over the last decade have clarified the
      mechanisms involved in cancer growth, invasion, and metastasis, and enabled the
      development of molecular-targeted agents. To date, sorafenib is the only
      molecular-targeted agent whose survival benefit has been demonstrated in two
      global phase III randomized controlled trials, and has been approved worldwide.
      Phase III clinical trials of other molecular targeted agents comparing them with
      sorafenib as first-line treatment agents are ongoing. Those agents target the
      vascular endothelial growth factor, platelet-derived growth factor receptors, as
      well as target the epidermal growth factor receptor, insulin-like growth factor
      receptor and mammalian target of rapamycin, in addition to other molecules
      targeting other components of the signal transduction pathways. In addition, the
      combination of sorafenib with standard treatment, such as resection, ablation,
      transarterial embolization, and hepatic arterial infusion chemotherapy are
      ongoing. This review outlines the main pathways involved in the development and
      progression of hepatocellular carcinoma and the new agents that target these
      pathways. Finally, the current statuses of clinical trials of new agents or
      combination therapy with sorafenib and standard treatment will also be discussed.

PMID- 23155331
TI  - PNPLA3, the triacylglycerol synthesis/hydrolysis/storage dilemma, and
      nonalcoholic fatty liver disease.
AB  - Genome-wide and candidate gene association studies have identified several
      variants that predispose individuals to developing nonalcoholic fatty liver
      disease (NAFLD). However, the gene that has been consistently involved in the
      genetic susceptibility of NAFLD in humans is patatin-like phospholipase domain
      containing 3 (PNPLA3, also known as adiponutrin). A nonsynonymous single
      nucleotide polymorphism in PNPLA3 (rs738409 C/G, a coding variant that encodes an
      amino acid substitution  I148M) is significantly associated with fatty liver and
      histological disease severity, not only in adults but also in children.
      Nevertheless, how PNPLA3 influences the biology of fatty liver disease is still
      an open question. A recent article describes new aspects about PNPLA3
      gene/protein function and suggests that the  I148M variant promotes hepatic lipid
      synthesis due to a gain of function. We revise here the published data about the
      role of the  I148M variant in lipogenesis/lipolysis, and suggest putative areas
      of future research. For instance we explored in silico whether the rs738409 C or
      G alleles have the ability to modify miRNA binding sites and miRNA gene
      regulation, and we found that prediction of PNPLA3 target miRNAs shows two miRNAs
      potentially interacting in the 3'UTR region (hsa-miR-769-3p and hsa-miR-516a-3p).
      In addition, interesting unanswered questions remain to be explored. For example,
      PNPLA3 lies between two CCCTC-binding factor-bound sites that could be tested for
      insulator activity, and an intronic histone 3 lysine 4 trimethylation peak
      predicts an enhancer element, corroborated by the DNase I hypersensitivity site
      peak. Finally, an interaction between PNPLA3 and glycerol-3-phosphate
      acyltransferase 2 is suggested by data miming.

PMID- 23155332
TI  - Human endogenous retroviruses and cancer: causality and therapeutic
      possibilities.
AB  - A substantial part of the human genome is derived from transposable elements;
      remnants of ancient retroviral infections. Conservative estimates set the
      percentage of human endogenous retroviruses (HERVs) in the genome at 8%. For the
      most part, the interplay between mutations, epigenetic mechanisms and
      posttranscriptional regulations silence HERVs in somatic cells. We first
      highlight mechanisms by which activation of members of several HERV families may
      be associated with tumor development before discussing the arising chances for
      both diagnosis and therapy. It has been shown that at least in some cases, tumor
      cells expressing HERV open reading frames (ORFs) thus gain tumor-promoting
      functions. However, since these proteins are not expressed in healthy tissues,
      they become prime target structures. Of potential pharmacological interest are
      the prevention of HERV transposition, the inhibition of HERV-encoded protein
      expression and the interference with these proteins' activities. Evidence from
      recent studies unequivocally proves that HERV ORFs represent a very interesting
      source of novel tumor-specific antigens with even the potential to surpass entity
      boundaries. The development of new tumor (immune-) therapies is a very active
      field and true tumor-specific targets are of outstanding interest since they
      minimize the risk of autoimmunity and could reduce side effects. Finally, we
      postulate on main future research streams in order to stimulate discussion on
      this hot topic.

PMID- 23155334
TI  - Current progress in the treatment of chronic hepatitis C.
AB  - Over the last decade, the standard of care for the treatment of chronic hepatitis
      C has been the combination of pegylated-interferon-alfa (PEG-IFN) and ribavirin
      (RBV) which results in sustained virological response (SVR) rates of 75%-85% in
      patients with genotypes 2 or 3 but only of 40%-50% in patients with genotype 1.
      Currently, there are rapid and continuous developments of numerous new agents
      against hepatitis C virus (HCV), which are the focus of this review. Boceprevir
      and telaprevir, two first-generation NS3/4A HCV protease inhibitors, have been
      recently licensed in several countries around the world to be used in combination
      with PEG-IFN and RBV for the treatment of genotype 1 patients. Boceprevir or
      telaprevir based triple regimens, compared with the PEG-IFN/RBV combination,
      improve the SVR rates by 25%-31% in treatment-naive genotype 1 patients, by 40%
      64% in prior relapsers, by 33%-45% in prior partial responders and by 24%-28% in
      prior null responders. At the same time, the application of response-guided
      treatment algorithms according to the on-treatment virological response results
      in shortening of the total therapy duration to only 24 wk in 45%-55% of treatment
      naive patients. There are, however, several challenges with the use of the new
      triple combinations in genotype 1 patients, such as the need for immediate
      results of HCV RNA testing using sensitive quantitative assays, new and more
      frequent adverse events (anemia and dysgeusia for boceprevir; pruritus, rash and
      anemia for telaprevir), new drug interactions and increasing difficulties in
      compliance. Moreover, the SVR rates are still poor in very difficult to treat
      subgroups of genotype 1 patients, such as null responders with cirrhosis, while
      there is no benefit for patients who cannot tolerate PEG-IFN/RBV or who are
      infected with non-1 HCV genotype. Many newer anti-HCV agents of different classes
      and numerous combinations are currently under evaluation with encouraging
      results. Preliminary data suggest that the treatment of chronic HCV patients with
      well tolerated combinations of oral agents without PEG-IFN is feasible and may
      lead to a universal HCV cure over the next 5-10 years.

PMID- 23155335
TI  - High densities of serotonin and peptide YY cells in the colon of patients with
      lymphocytic colitis.
AB  - AIM: To investigate colonic endocrine cells in lymphocytic colitis (LC) patients.
      METHODS: Fifty-seven patients with LC were included. These patients were 41
      females and 16 males, with an average age of 49 years (range 19-84 years). Twenty
      seven subjects that underwent colonoscopy with biopsies were used as controls.
      These subjects underwent colonoscopy because of gastrointestinal bleeding or
      health worries, where the source of bleeding was identified as haemorrhoids or
      angiodysplasia. They were 19 females and 8 males with an average age of 49 years
      (range 18-67 years). Biopsies from the right and left colon were obtained from
      both patients and controls during colonoscopy. Biopsies were fixed in 4% buffered
      paraformaldehyde, embedded in paraffin and cut into 5 MUm-thick sections. The
      sections immunostained by the avidin-biotin-complex method for serotonin, peptide
      YY (PYY), pancreatic polypeptide (PP) enteroglucagon and somatostatin cells. The
      cell densities were quantified by computerised image analysis using Olympus
      software. RESULTS: The colon of both the patient and the control subjects were
      macroscopically normal. Histopathological examination of colon biopsies from
      controls revealed normal histology. All patients fulfilled the diagnosis criteria
      required for of LC: an increase in intraepithelial lymphocytes (> 20
      lymphocytes/100 epithelial cells) and surface epithelial damage with increased
      lamina propria plasma cells and absent or minimal crypt architectural
      distribution. In the colon of both patients and control subjects, serotonin-, PYY
      , PP-, enteroglucagon- and somatostatin-immunoreactive cells were primarily
      located in the upper part of the crypts of Lieberkuhn. These cells were basket-
      or flask-shaped. There was no statistically significant difference between the
      right and left colon in controls with regards to the densities of serotonin- and
      PYY-immunoreactive cells (P = 0.9 and 0.1, respectively). Serotonin cell density
      in the right colon in controls was 28.9 +/- 1.8 and in LC patients 41.6 +/- 2.6
      (P = 0.008). In the left colon, the corresponding figures were 28.5 +/- 1.9 and
      42.4 +/- 2.9, respectively (P = 0.009). PYY cell density in the right colon of
      the controls was 10.1 +/- 1 and of LC patients 41 +/- 4 (P = 0.00006). In the
      left colon, PYY cell density in controls was 6.6 +/- 1.2 and in LC patients 53.3
      +/- 4.6 (P = 0.00007). CONCLUSION: The change in serotonin cells could be caused
      by an interaction between immune cells and serotonin cells, and that of PYY
      density might be secondary.

PMID- 23155333
TI  - Celiac disease: prevalence, diagnosis, pathogenesis and treatment.
AB  - Celiac disease (CD) is one of the most common diseases, resulting from both
      environmental (gluten) and genetic factors [human leukocyte antigen (HLA) and non
      HLA genes]. The prevalence of CD has been estimated to approximate 0.5%-1% in
      different parts of the world. However, the population with diabetes, autoimmune
      disorder or relatives of CD individuals have even higher risk for the development
      of CD, at least in part, because of shared HLA typing. Gliadin gains access to
      the basal surface of the epithelium, and interact directly with the immune
      system, via both trans- and para-cellular routes. From a diagnostic perspective,
      symptoms may be viewed as either "typical" or "atypical". In both positive
      serological screening results suggestive of CD, should lead to small bowel biopsy
      followed by a favourable clinical and serological response to the gluten-free
      diet (GFD) to confirm the diagnosis. Positive anti-tissue transglutaminase
      antibody or anti-endomysial antibody during the clinical course helps to confirm
      the diagnosis of CD because of their over 99% specificities when small bowel
      villous atrophy is present on biopsy. Currently, the only treatment available for
      CD individuals is a strict life-long GFD. A greater understanding of the
      pathogenesis of CD allows alternative future CD treatments to hydrolyse toxic
      gliadin peptide, prevent toxic gliadin peptide absorption, blockage of selective
      deamidation of specific glutamine residues by tissue, restore immune tolerance
      towards gluten, modulation of immune response to dietary gliadin, and restoration
      of intestinal architecture.

PMID- 23155336
TI  - Galactosylated chitosan/5-fluorouracil nanoparticles inhibit mouse hepatic cancer
      growth and its side effects.
AB  - AIM: To observe the curative effect of galactosylated chitosan (GC)/5
      fluorouracil (5-FU) nanoparticles in liver caner mice and its side effects.
      METHODS: The GC/5-FU nanoparticle is a nanomaterial made by coupling GC and 5-FU.
      The release experiment was performed in vitro. The orthotropic liver cancer mouse
      models were established and divided into control, GC, 5-FU and GC/5-FU groups.
      Mice in the control and GC group received an intravenous injection of 200 MUL
      saline and GC, respectively. Mice in the 5-FU and GC/5-FU groups received 200 MUL
      (containing 0.371 mg 5-FU) 5-FU and GC/5-FU, respectively. The tumor weight and
      survival time were observed. The cell cycle and apoptosis in tumor tissues were
      monitored by flow cytometry. The expression of p53, Bax, Bcl-2, caspase-3 and
      poly adenosine 50-diphosphate-ribose polymerase 1 (PARP-1) was detected by
      immunohistochemistry, reverse transcription-polymerase chain reaction and Western
      blot. The serum blood biochemical parameters and cytotoxic activity of natural
      killer (NK) cell and cytotoxicity T lymphocyte (CTL) were measured. RESULTS: The
      GC/5-FU nanoparticle is a sustained release system. The drug loading was 6.12% +/
      1.36%, the encapsulation efficiency was 81.82% +/- 5.32%, and the Zeta potential
      was 10.34 +/- 1.43 mV. The tumor weight in the GC/5-FU group (0.4361 +/- 0.1153 g
      vs 1.5801 +/- 0.2821 g, P < 0.001) and the 5-FU (0.7932 +/- 0.1283 g vs 1.5801 +/
      0.2821 g, P < 0.001) was significantly lower than that in the control group;
      GC/5-FU treatment can significantly lower the tumor weight (0.4361 +/- 0.1153 g
      vs 0.7932 +/- 0.1283 g, P < 0.001), and the longest median survival time was seen
      in the GC/5-FU group, compared with the control (12 d vs 30 d, P < 0.001), GC (13
      d vs 30 d, P < 0.001) and 5-FU groups (17 d vs 30 d, P < 0.001). Flow cytometry
      revealed that compared with the control, GC/5-FU caused a higher rate of G0-G1
      arrest (52.79% +/- 13.42% vs 23.92% +/- 9.09%, P = 0.014 ) and apoptosis (2.55%
      +/- 1.10% vs 11.13% +/- 11.73%, P < 0.001) in hepatic cancer cells. Analysis of
      the apoptosis pathways showed that GC/5-FU upregulated the expression of p53 at
      both the protein and the mRNA levels, which in turn lowered the ratio of Bcl
      2/Bax expression; this led to the release of cytochrome C into the cytosol from
      the mitochondria and the subsequent activation of caspase-3. Upregulation of
      caspase-3 expression decreased the PARP-1 at both the mRNA and the protein
      levels, which contributed to apoptosis. 5-FU increased the levels of aspartate
      aminotransferase and alanine aminotransferase, and decreased the numbers of
      platelet, white blood cell and lymphocyte and cytotoxic activities of CTL and NK
      cells, however, there were no such side effects in the GC/5-FU group. CONCLUSION:
      GC/5-FU nanoparticles can significantly inhibit the growth of liver cancer in
      mice via the p53 apoptosis pathway, and relieve the side effects and
      immunosuppression of 5-FU.

PMID- 23155337
TI  - Small intestine contrast ultrasonography vs computed tomography enteroclysis for
      assessing ileal Crohn's disease.
AB  - AIM: To compare computed tomography enteroclysis (CTE) vs small intestine
      contrast ultrasonography (SICUS) for assessing small bowel lesions in Crohn's
      disease (CD), when using surgical pathology as gold standard. METHODS: From
      January 2007 to July 2008, 15 eligible patients undergoing elective resection of
      the distal ileum and coecum (or right colon) were prospectively enrolled. All
      patients were under follow-up. The study population included 6 males and 9
      females, with a median age of 44 years (range: 18-80 years). INCLUSION CRITERIA:
      (1) certain diagnosis of small bowel requiring elective ileo-colonic resection;
      (2) age between 18-80 years; (3) elective surgery in our Surgical Unit; and (4)
      written informed consent. SICUS and CTE were performed <= 3 mo before surgery,
      followed by surgical pathology. The following small bowel lesions were blindly
      reported by one sonologist, radiologist, surgeon and histolopathologist: disease
      site, extent, strictures, abscesses, fistulae, small bowel dilation. Comparison
      between findings at SICUS, CTE, surgical specimens and histological examination
      was made by assessing the specificity, sensitivity and accuracy of each
      technique, when using surgical findings as gold standard. RESULTS: Among the 15
      patients enrolled, CTE was not feasible in 2 patients, due to urgent surgery in
      one patients and to low compliance in the second patient, refusing to perform CTE
      due to the discomfort related to the naso-jejunal tube. The analysis for
      comparing CTE vs SICUS findings was therefore performed in 13 out of the 15 CD
      patients enrolled. Differently from CTE, SICUS was feasible in all the 15
      patients enrolled. No complications were observed when using SICUS or CTE.
      Surgical pathology findings in the tested population included: small bowel
      stricture in 13 patients, small bowel dilation above ileal stricture in 10
      patients, abdominal abscesses in 2 patients, enteric fistulae in 5 patients,
      lymphnodes enlargement (> 1 cm) in 7 patients and mesenteric enlargement in 9
      patients. In order to compare findings by using SICUS, CTE, histology and
      surgery, characteristics of the small bowel lesions observed in CD each patient
      were blindly reported in the same form by one gastroenterologist-sonologist,
      radiologist, surgeon and anatomopathologist. At surgery, lesions related to CD
      were detected in the distal ileum in all 13 patients, also visualized by both
      SICUS and CTE in all 13 patients. Ileal lesions > 10 cm length were detected at
      surgery in all the 13 CD patients, confirmed by SICUS and CTE in the same 12 out
      of the 13 patients. When using surgical findings as a gold standard, SICUS and
      CTE showed the exactly same sensitivity, specificity and accuracy for detecting
      the presence of small bowel fistulae (accuracy 77% for both) and abscesses
      (accuracy 85% for both). In the tested CD population, SICUS and CTE were also
      quite comparable in terms of accuracy for detecting the presence of small bowel
      strictures (92% vs 100%), small bowel fistulae (77% for both) and small bowel
      dilation (85% vs 82%). CONCLUSION: In our study population, CTE and the non
      invasive and radiation-free SICUS showed a comparable high accuracy for assessing
      small bowel lesions in CD.

PMID- 23155338
TI  - Quasispecies dynamics in main core epitopes of hepatitis B virus by ultra-deep
      pyrosequencing.
AB  - AIM: To investigate the variability of the main immunodominant motifs of
      hepatitis B virus (HBV) core gene by ultra-deep-pyrosequencing (UDPS). METHODS:
      Four samples (2 genotype A and 2 genotype D) from 4 treatment-naive patients were
      assessed for baseline variability. Two additional samples from one patient
      (patient 4, genotype D) were selected for analysis: one sample corresponded to a
      36-mo treatment-free period from baseline and the other to the time of viral
      breakthrough after 18 mo of lamivudine treatment. The HBV region analyzed covered
      amino acids 40 to 95 of the core gene, and included the two main epitopic
      regions, Th50-69 and B74-84. UDPS was carried out in the Genome Sequencer FLX
      system (454 Life Sciences, Roche). After computer filtering of UDPS data based on
      a Poisson statistical model, 122,813 sequences were analyzed. The most conserved
      position detected by UDPS was analyzed by site-directed mutagenesis and evaluated
      in cell culture. RESULTS: Positions with highest variability rates were mainly
      located in the main core epitopes, confirming their role as immune-stimulating
      regions. In addition, the distribution of variability showed a relationship with
      HBV genotype. Patient 1 (genotype A) presented the lowest variability rates and
      patient 2 (genotype A) had 3 codons with variability higher than 1%. Patient 3
      and 4 (both genotype D) presented 5 and 8 codons with variability higher than 1%,
      respectively. The median baseline frequencies showed that genotype A samples had
      higher variability in epitopic positions than in the other positions analyzed,
      approaching significance (P = 0.07, sample 1 and P = 0.05, sample 2). In
      contrast, there were no significant differences in variability between the
      epitopic and other positions in genotype D cases. Interestingly, patient 1
      presented a completely mutated motif from amino acid 64 to 67 (E64LMT67), which
      is commonly recognized by T helper cells. Additionally, the variability observed
      in all 4 patients was particularly associated with the E64LMT67 motif. Codons 78
      and 79 were highly conserved in all samples, in keeping with their involvement in
      the interaction between the HBV virion capsid and the surface antigens (HBsAg).
      Of note, codon 76 was even more conserved than codons 78 and 79, suggesting a
      possible role in HBsAg interactions or even in hepatitis B e antigen
      conformation. Sequential analysis of samples from patient 4 (genotype D)
      illustrated the dynamism of the HBV quasispecies, with strong selection of one
      minor baseline variant coinciding with a decrease in core variability during the
      treatment-free and lamivudine-treated period. The drop in variability seemed to
      result from a "steady state" situation of the HBV quasispecies after selection of
      the variant with greatest fitness. CONCLUSION: Host immune pressure seems to be
      the main cause of HBV core evolution. UDPS analysis is a useful technique for
      studying viral quasispecies.

PMID- 23155339
TI  - Cost of treating chronic hepatitis B: comparison of current treatment guidelines.
AB  - AIM: To compare program costs of chronic hepatitis B (CHB) screening and
      treatment using Australian and other published CHB treatment guidelines. METHODS:
      Economic modeling demonstrated that in Australia a strategy of hepatocellular
      cancer (HCC) prevention in patients with CHB is more cost-effective than current
      standard care, or HCC screening. Based upon this model, we developed the B
      positive program to optimize CHB management of Australians born in countries of
      high CHB prevalence. We estimated CHB program costs using the B positive program
      algorithm and compared them to estimated costs of using the CHB treatment
      guidelines published by the Asian-Pacific, American and European Associations for
      the Study of Liver Disease (APASL, AASLD, EASL) and those suggested by an
      independent United States hepatology panel. We used a Markov model that factored
      in the costs of CHB screening and treatment, individualized by viral load and
      alanine aminotransferase levels, and calculated the relative costs of program
      components. Costs were discounted by 5% and calculated in Australian dollars
      (AUD). RESULTS: Using the B positive algorithm, total program costs amount to
      13,979,224 AUD, or 9634 AUD per patient. The least costly strategy is based upon
      using the AASLD guidelines, which would cost 34% less than our B positive
      algorithm. Using the EASL and the United States Expert Group guidelines would
      increase program costs by 46%. The largest expenditure relates to the cost of
      drug treatment (66.9% of total program costs). The contribution of CHB
      surveillance (20.2%) and HCC screening and surveillance (6.6%) is small--and
      together they represent only approximately a quarter of the total program costs.
      CONCLUSION: The significant cost variations in CHB screening and treatment using
      different guidelines are relevant for clinicians and policy makers involved in
      designing population-based disease control programs.

PMID- 23155340
TI  - Anemia after gastrectomy for early gastric cancer: long-term follow-up
      observational study.
AB  - AIM: To identify the incidence and etiology of anemia after gastrectomy in
      patients with long-term follow-up after gastrectomy for early gastric cancer.
      METHODS: The medical records of those patients with early gastric adenocarcinoma
      who underwent curative gastrectomy between January 2006 and October 2007 were
      reviewed. Patients with anemia in the preoperative workup, cancer recurrence,
      undergoing systemic chemotherapy, with other medical conditions that can cause
      anemia, or treated during follow up with red cell transfusions or supplements for
      anemia were excluded. Anemia was defined by World Health Organization criteria
      (Hb < 12 g/dL in women and < 13 g/dL in men). Iron deficiency was defined as
      serum ferritin < 20 MUg/dL. Vitamin B12 deficiency was defined as serum vitamin
      B12 < 200 pg/mL. Iron deficiency anemia was defined as anemia with concomitant
      iron deficiency. Anemia from vitamin B12 deficiency was defined as megaloblastic
      anemia (mean cell volume > 100 fL) with vitamin B12 deficiency. The profile of
      anemia over 48 mo of follow-up was analyzed. RESULTS: One hundred sixty-one
      patients with gastrectomy for early gastric cancer were analyzed. The incidence
      of anemia was 24.5% at 3 mo after surgery and increased up to 37.1% at 48 mo
      after surgery. The incidence of iron deficiency anemia increased during the
      follow up and became the major cause of anemia at 48 mo after surgery. Anemia of
      chronic disease and megaloblastic anemia were uncommon. The incidence of anemia
      in female patients was significantly higher than in male patients at 12 (40.0% vs
      22.0%, P = 0.033), 24 (45.0% vs 25.0%, P = 0.023), 36 (55.0% vs 28.0%, P =
      0.004), and 48 mo (52.0% vs 31.0%, P = 0.022) after surgery. Patients with total
      gastrectomy showed significantly higher incidence of anemia than patients with
      subtotal gastrectomy at 48 mo after surgery (60.7% vs 31.3%, P = 0.008). The
      incidence of iron deficiency was significantly higher in female patients than in
      male patients at 6 (35.4% vs 13.3%, P = 0.002), 12 (45.8% vs 16.8%, P < 0.001),
      18 (52.1% vs 22.3%, P < 0.001), 24 (60.4% vs 20.9%, P < 0.001), 36 (62.5% vs
      29.2%, P < 0.001), and 48 mo (66.7% vs 34.7%, P = 0.001) after surgery.
      CONCLUSION: Anemia was frequent after gastrectomy for early gastric cancer, with
      iron deficiency being the major cause. Evaluation for anemia including iron
      status should be performed after gastrectomy and appropriate iron replacement
      should be considered.

PMID- 23155341
TI  - Association of chronic viral hepatitis B with insulin resistance.
AB  - AIM: To investigate the relationship between chronic viral hepatitis B (CVHB) and
      insulin resistance (IR) in Korean adults. METHODS: A total of 7880 adults (3851
      men, 4029 women) who underwent a comprehensive medical examination were enrolled
      in this study. Subjects diagnosed with either diabetes mellitus, or any other
      disorder that could influence their insulin sensitivity, were rejected.
      Anthropometry, metabolic risk factors, hepatitis B surface antigen, hepatitis B
      surface antibody, hepatitis B core antibody, fasting plasma glucose and insulin
      were measured for all subjects. Homeostasis model assessment (HOMA), quantitative
      insulin check index (QUICKI), and Mf(fm) index were used for determining insulin
      sensitivity. Each participant was categorized into a negative, recovery, or CVHB
      group. To compare variables between groups, a t-test and/or one-way analysis of
      variance were used. Partial correlation coefficients were computed to present the
      association between insulin resistance and other variables. Multiple logistic
      regression analysis was used to assess the independent association between CVHB
      and IR. RESULTS: The mean age of men and women were 48.9 and 48.6 years,
      respectively. Subjects in the CVHB group had significantly higher waist
      circumference [(86.0 +/- 7.7 cm vs 87.3 +/- 7.8 cm, P = 0.004 in men), (78.3 +/-
      8.6 cm vs 80.5 +/- 8.5 cm, P < 0.001 in women)], cystatin C [(0.96 +/- 0.15 mg/dL
      vs 1.02 +/- 0.22 mg/dL, P < 0.001 in men), (0.84 +/- 0.15 mg/dL vs 0.90 +/- 0.16
      mg/dL, P < 0.001 in women)], fasting insulin [(5.47 +/- 3.38 MUU/mL vs 6.12 +/-
      4.62 MUU/mL, P < 0.001 in men), (4.57 +/- 2.82 MUU/mL vs 5.06 +/- 3.10 MUU/mL, P
      < 0.001 in women)] and HOMA index [(1.24 +/- 0.86 vs 1.43 +/- 1.24, P < 0.001 in
      men), (1.02 +/- 0.76 vs 1.13 +/- 0.87, P = 0.033 in women)] compared to control
      group. The HOMA index revealed a positive correlation with body mass index (BMI)
      (r = 0.378, P < 0.001), waist circumference (r =0.356, P < 0.001), percent body
      fat (r = 0.296, P < 0.001), systolic blood pressure (r = 0.202, P < 0.001), total
      cholesterol (r = 0.134, P < 0.001), triglycerides (r = 0.292, P < 0.001),
      cystatin C (r = 0.069, P < 0.001) and uric acid (r = 0.142, P < 0.001). The
      QUICKI index revealed a negative correlation with BMI (r = -0.254, P < 0.001),
      waist circumference (r = 0-0.243, P < 0.001), percent body fat (r = -0.217, P <
      0.001), systolic blood pressure (r = -0.132, P < 0.001), total cholesterol (r = 
      0.106, P < 0.001), triglycerides (r = -0.205, P < 0.001), cystatin C (r = -0.044,
      P < 0.001) and uric acid (r = -0.096, P < 0.001). For subjects identified with
      IR, the odds ratio of an accompanying diagnosis of chronic hepatitis B was 1.534
      (95% CI: 1.158-2.031, HOMA index criteria) or 1.566 (95% CI: 1.124-2.182, QUICKI
      criteria) after adjustment for age, gender, BMI, and amount of alcohol
      consumption. CONCLUSION: Our study demonstrates that CVHB is associated with IR.
      CVHB may need to be monitored for occurrence of IR and diabetes mellitus.

PMID- 23155342
TI  - Treatment of functional dyspepsia with sertraline: a double-blind randomized
      placebo-controlled pilot study.
AB  - AIM: To evaluate sertraline, a selective serotonin reuptake inhibitor in the
      treatment of patients with functional dyspepsia. METHODS: Consecutive tertiary
      hospital patients with a clinical diagnosis of functional dyspepsia (FD)
      according to the Rome II criteria with a Hong Kong dyspepsia index (HKDI) of
      greater than 16 were recruited. Patients commenced enrolment prior to the
      inception of the Rome III criteria for functional dyspepsia. All patients were
      ethnic Chinese, had a normal upper endoscopy and were Helicobacter pylori
      negative prior to enrolment. Study patients were randomized to receive sertraline
      50 mg or placebo daily for 8 wk. HKDI symptom scores, quality of life, hospital
      anxiety and depression (HAD) scale and global symptom relief were evaluated
      before, during and after treatment. Adverse effects were monitored during and
      after treatment. RESULTS: A total of 193 patients were randomized in the
      intention to treat (ITT), and 150 patients were included in the per protocol (PP)
      analysis. In both the ITT and PP, there was no difference in the primary outcome
      of global dyspepsia symptoms between the sertraline and placebo groups at week 8.
      In the ITT analysis, 98 and 95 patients were randomized to the sertraline and
      placebo groups respectively. A total of 43 patients withdrew from the study
      (22.3%) by week 8, with 23 of the 24 drop-outs in the sertraline group occurring
      prior to week 4 (95.8%). In contrast, in the placebo arm, 11 of 19 patients
      dropped out by week 4 (57.9%). Utilizing the last response carried forward to
      account for the drop-outs, there were no differences between the sertraline and
      placebo groups at baseline in terms of the HKDI, HKDI 26.08 +/- 6.19 vs 26.70 +/-
      5.89, P = 0.433; and at week 8, HKDI 22.41 +/- 6.36 vs 23.25 +/- 7.30, P = 0.352
      respectively. In the PP analysis, 74 and 76 patients were randomized to the
      sertraline and placebo groups respectively. At baseline, there were no
      statistically significant differences between the sertraline and placebo groups,
      HKDI 25.83 +/- 6.313 vs 27.19 +/- 5.929 respectively, P = 0.233; however by week
      8, patients in the sertraline group demonstrated a statistically significant
      difference in their Hong Kong Dyspepsia Index compared to placebo, HKDI 20.53 +/-
      6.917 vs 23.34 +/- 7.199, P = 0.02, respectively). There was also no
      statistically significant difference in overall quality of life measures or the
      HAD scale related to treatment in either the ITT or PP analysis at week 8.
      CONCLUSION: This pilot study, the first to examine sertraline, a selective
      serotonin reuptake inhibitor, for the management of FD, did not find that it was
      superior to placebo.

PMID- 23155343
TI  - Transcatheter arterial chemoembolization for gastrointestinal stromal tumors with
      liver metastases.
AB  - AIM: To evaluate the efficacy and safety of transcatheter arterial
      chemoembolization (TACE) for gastrointestinal stromal tumor (GIST) with liver
      metastases after the failure of tyrosine kinase inhibitors (TKIs). METHODS:
      Patients with histologically confirmed CD117-positive GIST with liver metastases
      who were resistant and/or intolerant to prior imatinib and/or sunitinib and who
      received TACE for at least one treatment cycle or only best supportive care and
      TKI reintroduction were eligible for the study. The patients were divided into
      two groups: those in TACE group received TACE treatment containing 5-20 mL
      iodized oil and 40-80 mg doxorubicin hydrochloride and TKI reintroduction or best
      supportive care, those in control group only received TKI reintroduction or best
      supportive care. The primary end-point was overall survival and the secondary end
      points were, progression-free survival (PFS), response rates, and safety.
      RESULTS: Sixty patients admitted between June 2008 and October 2011 were eligible
      for this study, including 22 in TACE group and 38 in control group. In the TACE
      group, 12 (54.5%) achieved liver partial response, 5 (22.7%) had stable disease,
      and 5 (22.7%) had liver progressive disease. Disease control rate of liver
      metastases was 77.3% in the TACE group and 39.5% in the control group. The median
      liver PFS in TACE group was 47.1 wk (95% CI: 23.9-70.3). The median PFS in TACE
      group was longer than in control group (30.0 wk, 95% CI: 20.1-39.9 vs 12.9 wk,
      95% CI: 11.9-13.9) (P = 0.0001). The median overall survival in TACE group was
      also longer than in control group (68.5 wk, 95% CI: 57.4-79.6 vs 25.7 wk, 95% CI:
      23.2-28.2) (P = 0.0001). TACE treatment significantly reduced the risk of death
      (hazard ratio: 0.109). Patients without extrahepatic metastases treated with TACE
      had significantly better prognosis. Most of the adverse events were of grade 1 or
      2 and tolerable. CONCLUSION: TACE is effective and well tolerated in GIST
      patients with liver metastases after TKI failure, and it may be an optional
      treatment for this disease.

PMID- 23155344
TI  - Liver-protecting effects of omega-3 fish oil lipid emulsion in liver
      transplantation.
AB  - AIM: To investigate the liver-protecting effect of parenteral nutrition (PN)
      support with omega-3 fatty acids in a randomized controlled clinical trial.
      METHODS: Sixty-six patients with the diagnosis of end-stage liver disease or
      hepatic cellular carcinoma were admitted to the Affiliated Drum Tower Hospital,
      Nanjing University, China for orthotopic liver transplantation. The patients were
      randomly divided into two groups: PN group (n = 33) and polyunsaturated fatty
      acid (PUFA) group (n = 33). All patients received isocaloric and isonitrogenous
      PN for seven days after surgery, and in PUFA group omega-3 fish oil lipid
      emulsion replaced part of the standard lipid emulsion. Liver function was tested
      on days 2 and 9 after surgery. Pathological examination was performed after
      reperfusion of the donor liver and on day 9. Clinical outcome was assessed based
      on the post-transplant investigations, including: (1) post-transplant mechanical
      ventilation; (2) total hospital stay; (3) infectious morbidities; (4) acute and
      chronic rejection; and (5) mortality (intensive care unit mortality, hospital
      mortality, 28-d mortality, and survival at a one-year post-transplant
      surveillance period). RESULTS: On days 2 and 9 after operation, a significant
      decrease of alanine aminotransferase (299.16 U/L +/- 189.17 U/L vs 246.16 U/L +/-
      175.21 U/L, P = 0.024) and prothrombin time (5.64 s +/- 2.06 s vs 2.54 s +/- 1.15
      s, P = 0.035) was seen in PUFA group compared with PN group. The pathological
      results showed that omega-3 fatty acid supplement improved the injury of hepatic
      cells. Compared with PN group, there was a significant decrease of post
      transplant hospital stay in PUFA group (18.7 d +/- 4.0 d vs 20.6 d +/- 4.6 d, P =
      0.041). Complications of infection occurred in 6 cases of PN group (2 cases of
      pneumonia, 3 cases of intra-abdominal abscess and 1 case of urinary tract
      infection), and in 3 cases of PUFA group (2 cases of pneumonia and 1 case of
      intra-abdominal abscess). No acute or chronic rejection and hospital mortality
      were found in both groups. The one-year mortality in PN group was 9.1% (3/33),
      one died of pulmonary infection, one died of severe intra-hepatic cholangitis and
      hepatic dysfunction and the other died of hepatic cell carcinoma recurrence. Only
      one patient in PUFA group (1/33, 3.1%) died of biliary complication and hepatic
      dysfunction during follow-up. CONCLUSION: Post-transplant parenteral nutritional
      support combined with omega-3 fatty acids can significantly improve the liver
      injury, reduce the infectious morbidities, and shorten the post-transplant
      hospital stay.

PMID- 23155345
TI  - Colorectal cancer lymph node staining by activated carbon nanoparticles
      suspension in vivo or methylene blue in vitro.
AB  - AIM: To investigate whether activated carbon nanoparticles suspension (ACNS) or
      methylene blue (MB) can increase the detected number of lymph nodes in colorectal
      cancer. METHODS: Sixty-seven of 72 colorectal cancer patients treated at our
      hospital fulfilled the inclusion criteria of the study which was conducted from
      December 2010 to February 2012. Seven patients refused to participate.
      Eventually, 60 patients were included, and randomly assigned to three groups (20
      in each group): ACNS group (group A), MB group (group B) and non-stained
      conventional surgical group (group C). In group A, patients received subserosal
      injection of 1 mL ACNS in a 4-quadrant region around the mass. In group B, the
      main artery of specimen was identified and isolated after the specimen was
      removed, and 2 mL MB was slowly injected into the isolated, stretched and fixed
      vessel. In group C, no ACNS and MB were injected. All the mesentery lymph nodes
      were isolated and removed systematically by visually inspecting and palpating the
      adipose tissue. RESULTS: No difference was observed among the three groups in
      age, gender, tumor location, tumor diameter, T-stage, degree of differentiation,
      postoperative complications and peritoneal drainage retention time. The total
      number of detected lymph nodes was 535, 476 and 223 in the three groups,
      respectively. The mean number of detected lymph nodes per patient was
      significantly higher in group A than in group C (26.8 +/- 8.4 vs 12.2 +/- 3.2, P
      < 0.001). Similarly, there were significantly more lymph nodes detected in group
      B than in group C (23.8 +/- 6.9 vs 12.2 +/- 3.2, P < 0.001). However, there was
      no significant difference between group A and group B. There were 50, 46 and 32
      metastatic lymph nodes dissected in 13 patients of group A, 10 patients of group
      B and 11 patients of group C, without significant differences among the three
      groups. Eleven of the 60 patients had insufficient number of detected lymph nodes
      (< 12). Only one patient with T(4a) rectal cancer had 10 lymph nodes detected in
      group B, the other 10 patients were all from group C. Based on the different
      diameter categories, the number of detected lymph nodes in groups A and B was
      significantly higher than in group C. However, there was no statistically
      significant difference between group A and group B. The metastatic lymph nodes
      were not significant different among the three groups. Similarly, tumor location,
      T stage and tumor differentiation did not affect the staining results. Body mass
      index was a minor influencing factor in the two different staining methods. The
      stained lymph nodes can easily be identified from the mesenteric adipose tissues,
      and the staining time for lymph nodes was not significantly different compared
      with unstained group. None of the patients in groups A and B had drug-related
      complications. CONCLUSION: Both activated carbon nanoparticles suspension in vivo
      and methylene blue in vitro can be used as tracers to increase the detected
      number of lymph nodes in colorectal cancer.

PMID- 23155346
TI  - Inverted Meckel's diverticulum as a cause of occult lower gastrointestinal
      hemorrhage.
AB  - Meckel's diverticulum is a common asymptomatic congenital gastrointestinal
      anomaly, but rarely it can present with hemorrhage. Over the last few years
      inverted Meckel's diverticulum has been reported in the literature with
      increasing frequency as an occult source of lower gastrointestinal hemorrhage.
      Here, we report a case of a 54-year-old male, who was referred for surgical
      evaluation with persistent anemia and occult blood per rectum after a work up
      which failed to localize the source over 12 mo, including upper and capsule
      endoscopy, colonoscopy, enteroclysis, Meckel scan, and tagged nuclear red blood
      cell scan. An abdominal computed tomography scan showed a possible mid-ileal
      intussusception and intraluminal mass. During the abdominal exploration, inverted
      Meckel's diverticulum was diagnosed and resected. We review the literature,
      discuss the forms in which the disease presents, the diagnostic modalities
      utilized, pathological findings, and treatment. Although less than 40 cases have
      been reported in the English literature from 1978 to 2005, 19 cases have been
      reported in the last 6 years alone (2006-2012) due to improved diagnostic
      modalities. Successful diagnosis and treatment of this disease requires a high
      index of clinical suspicion, which is becoming increasingly relevant to general
      gastroenterologists.

PMID- 23155347
TI  - Enterolithiasis-associated ileus in Crohn's disease.
AB  - Stasis of the flow of the intestinal contents, ingested material and unfavorable
      composition of the chylus can lead to the formation of enteroliths inside the
      bowel. Enterolithiasis represents a rare disorder of the gastrointestinal tract
      that can be associated with intermittent abdominal pain or more serious
      complications such as bleeding or obstruction. Enterolithiasis in Crohn's disease
      represents an extremely rare condition and usually occurs only in patients with a
      long symptomatic history of Crohn's disease. We report an unusual case of
      enterolithiasis-related intestinal obstruction in a young male patient with
      Crohn's disease (A2L3B1 Montreal Classification for Crohn's disease 2005)
      undergoing emergency laparotomy and ileocoecal resection. In addition, we present
      an overview of the relevant characteristics of enterolithiasis on the basis of
      the corresponding literature.

PMID- 23155348
TI  - An aortoduodenal fistula as a complication of immunoglobulin G4-related disease.
AB  - Most primary aortoduodenal fistulas occur in the presence of an aortic aneurysm,
      which can be part of immunoglobulin G4 (IgG4)-related sclerosing disease. We
      present a case who underwent endovascular grafting of an aortoduodenal fistula
      associated with a high serum IgG4 level. A 56-year-old male underwent urgent
      endovascular reconstruction of an aortoduodenal fistula. The patient received
      antibiotics and other supportive therapy, and the postoperative course was
      uneventful, however, elevated levels of serum IgG, IgG4 and C-reactive protein
      were noted, which normalized after the introduction of steroid therapy. Control
      computed tomography angiography showed no endoleaks. The primary aortoduodenal
      fistula may have been associated with IgG4-related sclerosing disease as a
      possible complication of IgG4-related inflammatory aortic aneurysm. Endovascular
      grafting of a primary aortoduodenal fistula is an effective and minimally
      invasive alternative to standard surgical repair.

PMID- 23155349
TI  - Should anticoagulants be administered for portal vein thrombosis associated with
      acute pancreatitis?
AB  - Venous complications in patients with acute pancreatitis typically occur as a
      form of splenic, portal, or superior mesenteric vein thrombosis and have been
      detected more frequently in recent reports. Although a well-organized protocol
      for the treatment of venous thrombosis has not been established, anticoagulation
      therapy is commonly recommended. A 73-year-old man was diagnosed with acute
      progressive portal vein thrombosis associated with acute pancreatitis. After one
      month of anticoagulation therapy, the patient developed severe hematemesis. With
      endoscopy and an abdominal computed tomography scan, hemorrhages in the
      pancreatic pseudocyst, which was ruptured into the duodenal bulb, were confirmed.
      After conservative treatment, the patient was stabilized. While the rupture of a
      pseudocyst into the surrounding viscera is a well-known phenomenon, spontaneous
      rupture into the duodenum is rare. Moreover, no reports of upper gastrointestinal
      bleeding caused by pseudocyst rupture in patients under anticoagulation therapy
      for venous thrombosis associated with acute pancreatitis have been published.
      Herein, we report a unique case of massive upper gastrointestinal bleeding due to
      pancreatic pseudocyst rupture into the duodenum, which developed during
      anticoagulation therapy for portal vein thrombosis associated with acute
      pancreatitis.

PMID- 23155350
TI  - Postoperative retroperitoneal desmoid tumor mimics recurrent gastrointestinal
      stromal tumor: a case report.
AB  - Desmoid tumor is a locally invasive, myofibroblastic, nonmetastatic tumor. Its
      pathogenesis remains unclear and it may involve genetic abnormalities, sex
      hormones and traumatic injury, including surgery. Postoperative intra-abdominal
      desmoid tumor is rare, especially in the retroperitoneum. We report a case of
      postoperative retroperitoneal desmoid tumor that developed 29 mo after the first
      excision of a gastrointestinal stromal tumor. Sporadic trauma-related intra
      abdominal desmoid tumors reported in the English literature are also reviewed.
      Despite an extremely low incidence, postoperative desmoid tumor should be
      considered in the differential diagnosis when a recurrent neoplasm is found at
      least one year after operation. However, it is a clinical challenge to
      distinguish recurrent malignant neoplasms from desmoid tumors, and surgical
      resection is the treatment option depending on the anatomic location.

PMID- 23155351
TI  - Penalized Nonlinear Least Squares Estimation of Time-Varying Parameters in
      Ordinary Differential Equations.
AB  - Ordinary differential equations (ODEs) are widely used in biomedical research and
      other scientific areas to model complex dynamic systems. It is an important
      statistical problem to estimate parameters in ODEs from noisy observations. In
      this article we propose a method for estimating the time-varying coefficients in
      an ODE. Our method is a variation of the nonlinear least squares where penalized
      splines are used to model the functional parameters and the ODE solutions are
      approximated also using splines. We resort to the implicit function theorem to
      deal with the nonlinear least squares objective function that is only defined
      implicitly. The proposed penalized nonlinear least squares method is applied to
      estimate a HIV dynamic model from a real dataset. Monte Carlo simulations show
      that the new method can provide much more accurate estimates of functional
      parameters than the existing two-step local polynomial method which relies on
      estimation of the derivatives of the state function. Supplemental materials for
      the article are available online.

PMID- 23155352
TI  - Media and politics: Empirical data on their cross-influence in health policy.
AB  - OBJECTIVES: Despite the central influence of public policies on health and
      welfare, relatively little is known about actual health care policy-making
      processes. This presentation will offer preliminary results from a federally
      funded project aimed at gaining insights into the interrelations among interest
      group strategies, media discourses and political debates in health care. The
      policy debate on health care privatization in Quebec is used as a case study. 
      APPROACH: Two sources of data were used: media sources and political debates.
      Media sources were the six main provincial newspapers in Quebec, two national
      newspapers and The Canadian Press, as well as transcripts from specific news
      related programs of three national television stations and two national radio
      stations. Political debates were obtained through transcripts of all question
      periods in the Parliament and debates in the standing committee on health.
      Sources were systematically searched to identify all relevant data. Multiple
      search syntaxes were developed and tested to maximize sensitivity and
      specificity. All data was entered and coded into qualitative analysis software. 
      RESULTS: Data was analyzed longitudinally from June 2005 to January 1, 2010. Four
      levels of results will be presented: 1) Descriptive analysis of the interest
      groups involved, their policy preferences and the rhetoric they employed to
      support their views. 2) Descriptive analysis of the main policy proposals that
      structured the debate as well as of the coalition of groups behind those
      proposals. 3) Graphic longitudinal analysis of the intensity of the debate and of
      the relative importance and evolution of various policy proposals. 4) Preliminary
      results on the nature, direction and level of inter-influence between the policy
      and media agendas.  CONCLUSION: This presentation provides empirical evidence on
      current policy-making processes in health care. It shows, unsurprisingly, that
      policy-making is a circumvoluted process of inter-influence among interest
      groups, politicians and the media. It also highlights the fact that scientific
      evidence actually plays a minor (if any) role in policy processes.

PMID- 23155353
TI  - Bothaella manhi, a new species of tribe Aedini (Diptera: Culicidae) from the Cuc
      Phuong National Park of Vietnam based on morphology and DNA sequence.
AB  - A new species of genus Bothaella (Diptera: Culicidae) collected along with two
      other species of the genus during surveys for flavivirus isolations in the Cuc
      Phuong National Park in northern Vietnam is formally described and named as
      Bothaella manhi, sp. n. The adults, pupa and fourth-instar larva are
      characterized, the male genitalia and the two immature stages are illustrated and
      DNA sequence data are included for regions coding for sections of the COI and
      COII genes (mtDNA). The species is compared and distinguished from the other
      species of the genus, and sequence data are used to hypothesise its phylogenetic
      relationship with Bo. helenae and Bo. kleini, the other two species collected
      during the survey.

PMID- 23155354
TI  - Target-target similarity on the attentional blink: Task-relevance matters!
AB  - Studies of the attentional blink (AB) indicate that similarity modulates the
      magnitude of the impairment in reporting the second of two masked targets. The
      present experiments tested whether similarity-based modulations of the AB are
      determined by all object dimensions or by task-relevant dimensions only.
      Similarity between target faces was manipulated on two dimensions, only one of
      which was task-relevant. The results indicated that similarity on the task
      relevant dimension modulated the AB, while similarity on task-irrelevant
      dimension did not. These results suggest that selection during the AB can occur
      on the level of task-relevant dimensions.

PMID- 23155355
TI  - Requirements for contractility in disordered cytoskeletal bundles.
AB  - Actomyosin contractility is essential for biological force generation, and is
      well understood in highly organized structures such as striated muscle.
      Additionally, actomyosin bundles devoid of this organization are known to
      contract both in vivo and in vitro, which cannot be described by standard muscle
      models. To narrow down the search for possible contraction mechanisms in these
      systems, we investigate their microscopic symmetries. We show that contractile
      behavior requires non-identical motors that generate large-enough forces to probe
      the nonlinear elastic behavior of F-actin. This suggests a role for filament
      buckling in the contraction of these bundles, consistent with recent experimental
      results on reconstituted actomyosin bundles.

PMID- 23155356
TI  - VEGF -634C/G genotype is predictive of long-term survival after treatment with a
      definitive 5-fluorouracil/cisplatin-based chemoradiotherapy in Japanese patients
      with esophageal squamous cell carcinoma.
AB  - BACKGROUND: Reports have been accumulating that genetic properties are predictive
      of clinical response after and/or toxicity during cancer chemotherapy, but little
      information is available concerning effects on long-term survival. In this study,
      49 Japanese patients with esophageal squamous cell carcinoma (ESCC) were followed
      up for 5 years after treatment with a definitive 5-fluorouracil (5-FU)/cisplatin
      (CDDP)-based chemoradiotherapy (CRT), and the effects of genotypes of vascular
      endothelial growth factor (VEGF) were retrospectively revaluated in terms of
      prediction of long-term survival. METHODS: A course consisted of the continuous
      infusion of 5-FU at 400 mg/m(2)/day for days 1-5 and 8-12, the infusion of CDDP
      at 40 mg/m(2)/day on days 1 and 8, and radiation at 2 Gy/day on days 1 to 5, 8 to
      12, and 15 to 19, with a second course repeated after a 2-week interval. The VEGF
      genotypes -1498T/C, -1154G/A, -634C/G, -7C/T, 936C/T, and 1612G/A were evaluated.
      RESULTS: The complete response (CR) rate was 46.9% (23/49). The 5-year survival
      rate was 42.9 % (21/49). There were 7 patients with a CR, but survival of less
      than 5 years. They died from myocardial infarction (N=1), sudden cardiac death
      after suffering from heart failure (N=1), acute myeloid leukemia that developed
      from myelodysplastic syndromes (N=1), factors not specified (N=2), oropharynx
      cancer (N=1), and tongue cancer (N=1). VEGF -634C/G had no effect on clinical
      response, but long-term survival depended on the genotype (p=0.033, Fisher's;
      p=0.038, Cochran-Armitage; p=0.079, Log-rank). The genotype frequency of 7
      patients with a CR, but survival of less than 5 years was different from that for
      the other 42 patients (p=0.032, Fisher's). None of the other 5 genotypes
      evaluated affected either clinical response or survival. CONCLUSIONS: VEGF 
      634C/G is possibly predictive of long-term survival after treatment with a
      definitive 5-FU/CDDP-based CRT. Further clinical studies with a larger number of
      cases are needed to clarify the effects of this genotype.

PMID- 23155357
TI  - Inhibitory effects of anthocyanins on secretion of Helicobacter pylori CagA and
      VacA toxins.
AB  - Anthocyanins have been studied as potential antimicrobial agents against
      Helicobacter pylori. We investigated whether the biosynthesis and secretion of
      cytotoxin-associated protein A (CagA) and vacuolating cytotoxin A (VacA) could be
      suppressed by anthocyanin treatment in vitro. H. pylori reference strain 60190
      (CagA(+)/VacA(+)) was used in this study to investigate the inhibitory effects of
      anthocyanins; cyanidin 3-O-glucoside (C3G), peonidin 3-O-glucoside (Peo3G),
      pelargonidin 3-O-glucoside (Pel3G), and malvidin 3-O-glucoside (M3G) on
      expression and secretion of H. pylori toxins. Anthocyanins were added to
      bacterial cultures and Western blotting was used to determine secretion of CagA
      and VacA. Among them, we found that C3G inhibited secretion of CagA and VacA
      resulting in intracellular accumulation of CagA and VacA. C3G had no effect on
      cagA and vacA expression but suppressed secA transcription. As SecA is involved
      in translocation of bacterial proteins, the down-regulation of secA expression by
      C3G offers a mechanistic explanation for the inhibition of toxin secretion. To
      our knowledge, this is the first report suggesting that C3G inhibits secretion of
      the H. pylori toxins CagA and VacA via suppression of secA transcription.

PMID- 23155358
TI  - Curative resection of hepatocellular carcinoma using modified Glissonean pedicle
      transection versus the Pringle maneuver: a case control study.
AB  - OBJECTIVE: The Glissonean pedicle transection method of liver resection has been
      found to shorten operative time and minimize intraoperative bleeding during liver
      segmentectomy. We have compared the feasibility, effectiveness, and safety of the
      Glissonean pedicle transection method with the Pringle maneuver in patients
      undergoing selective curative resection of large hepatocellualr carcinoma (HCC).
      METHODS: Eligible patients with large (> 5 cm) nodular HCC (n = 50) were assigned
      to undergo curative hepatectomy using the Glissonean pedicle transection method
      (n = 25) or the Pringle maneuver (n = 25). Partial interruption of the
      infrahepatic inferior vena cava was incorporated to further reduce bleeding from
      liver transection. The primary outcome measure was postoperative changes in liver
      function from baseline. Secondary outcomes included operating time, volume of
      intraoperative blood loss/transfusion, and time to resolution of ascites.
      RESULTS: The two groups were comparable in age, sex, site and size of the liver
      tumor, segment or lobe intended to be resected, and liver function reserve, and
      the results were not significant statistically. All patients underwent successful
      major hepatectomies using the assigned method, with the extent of major
      hepatectomy comparable in the two groups (P = 0.832). The Glissonean approach was
      associated with shorter hepatic inflow interruption (30.0 +/- 12.0 min vs. 45.0
      +/- 13.0 min, P < 0.001), lower volume of blood loss (145.0 +/- 20.0 mL vs. 298.0
      +/- 109.0 mL, P < 0.001), reduced requirement for transfusion (0.0 +/- 0.0 mL vs.
      200.0 +/- 109.0 mL, P < 0.0001), and more rapid resolution of ascites (9.5 +/-
      1.2 d vs. 15.3 +/- 2.4 d, P < 0.001). Postoperative liver function measures were
      comparable in the two groups, and the results were not significant statistically.
      CONCLUSION: The Glissonean pedicle transection method is a feasible, effective,
      and safe technique for hepatic inflow control during the curative resection of
      large nodular HCCs.

PMID- 23155359
TI  - Effect of low-level laser therapy on incorporation of block allografts.
AB  - OBJECTIVE: To assess the effect of low-level laser therapy (LLLT) on the
      incorporation of deep-frozen block allografts in a rabbit model. BACKGROUND DATA:
      Studies have shown that LLLT has beneficial effects on tissue repair and new bone
      formation. METHODS: Bone tissue was harvested from two rabbits, processed by deep
      freezing and grafted into the calvaria of 12 animals, which were then randomly
      allocated into two groups: experimental (L) and control (C). Rabbits in group L
      were irradiated with an aluminum gallium arsenide diode laser (AlGaAs; wavelength
      830 nm, 4 J/cm(2)), applied to four sites on the calvaria, for a total dose of 16
      J/cm(2) per session. The total treatment dose after eight sessions was 128
      J/cm(2). Animals were euthanized at 35 (n = 6) or 70 days (n = 6)
      postoperatively. RESULTS: Deep-freeze-processed block allografts followed by LLLT
      showed incorporation at the graft-host interface, moderate bone remodeling,
      partial filling of osteocyte lacunae, less inflammatory infiltrate in the early
      postoperative period, and higher collagen deposition than the control group.
      CONCLUSION: Optical microscopy and scanning electron microscopy showed that
      allograft bone processed by deep-freezing plus LLLT is suitable as an alternative
      for the treatment of bone defects. Use of the deep-freezing method for processing
      of bone grafts preserves the structural and osteoconductive characteristics of
      bone tissue.

PMID- 23155360
TI  - Bone morphogenetic protein-9 induces osteogenic differentiation of rat dental
      follicle stem cells in P38 and ERK1/2 MAPK dependent manner.
AB  - Dental follicle stem cells are a group of cells possessing osteogenic,
      adipogenetic and neurogenic differentiations, but the specific mechanism
      underlying the multilineage differentiation remains still unclear. Great
      attention has been paid to bone morphogenetic protein-9 (BMP-9) due to its potent
      osteogenic activity. In the present study, rat dental follicle stem cells were
      isolated and purified, and cells of passage 3 underwent adenovirus mediated BMP-9
      gene transfection to prepare dental follicle stem cells with stable BMP-9
      expression. Detection of alkaline phosphatase (ALP) and calcium deposition showed
      dental follicle stem cells transfected with BMP-9 gene could significantly
      promote the osteogenesis. In addition, SB203580 and PD98059 were employed to
      block the p38 mitogen-activated protein kinase (p38MAPK) and extracellular signal
      regulated kinase (ERK1/2), respectively. Detection of ALP and calcium deposition
      revealed the BMP-9 induced osteogenic differentiation of dental follicle stem
      cells depended on MAPK signaling pathway.

PMID- 23155361
TI  - Platelet Rich Fibrin (P.R.F.) in reconstructive surgery of atrophied maxillary
      bones: clinical and histological evaluations.
AB  - INTRODUCTION: Maxillary bone losses often require additional regenerative
      procedures: as a supplement to the procedures of tissue regeneration, a platelet
      concentrate called PRF (Platelet Rich Fibrin) was tested for the first time in
      France by Dr. Choukroun. Aim of the present study is to investigate, clinically
      and histologically, the potential use of PRF, associated with deproteinized
      bovine bone (Bio-Oss), as grafting materials in pre-implantology sinus grafting
      of severe maxillary atrophy, in comparison with a control group, in which only
      deproteinized bovine bone (Bio-Oss) was used as reconstructive material.
      MATERIALS AND METHODS: 60 patients were recruited using the cluster-sampling
      method; inclusion criteria were maxillary atrophy with residual ridge < 5mm. The
      major atrophies in selected patients involved sinus-lift, with a second-look
      reopening for the implant insertion phase. The used grafting materials were: a)
      Bio-Oss and b) amorphous and membranous PRF together with Bio-Oss. We performed
      all operations by means of piezosurgery in order to reduce trauma and to optimize
      the design of the operculum on the cortical bone. The reopening of the surgical
      area was scheduled at 3 different times. RESULTS: 72 sinus lifts were performed
      with subsequent implants insertions.We want to underline how the histological
      results proved that the samples collected after 106 days (Early protocol) with
      the adding of PRF were constituted by lamellar bone tissue with an interposed
      stroma that appeared relaxed and richly vascularized. CONCLUSIONS: The use of PRF
      and piezosurgery reduced the healing time, compared to the 150 days described in
      literature, favoring optimal bone regeneration. At 106 days, it is already
      possible to achieve good primary stability of endosseous implants, though lacking
      of functional loading.

PMID- 23155362
TI  - Molecular mechanism of SAHA on regulation of autophagic cell death in tamoxifen
      resistant MCF-7 breast cancer cells.
AB  - OBJECTIVE: Tamoxifen is currently used for the treatment of estrogen receptor
      positive breast cancer patients, but acquired resistance to tamoxifen is a
      critical problem in breast cancer therapy. Suberoylanilide hydroxamic acid (SAHA)
      is a prototype of the newly developed HDAC inhibitor. The aim of this study is to
      investigate the anticancer effects of SAHA in tamoxifen-resistant MCF-7 (TAMR/MCF
      7) cells. METHODS: Cytotoxicity, apoptosis and autophagic cell death induced by
      SAHA were studied. A TAMR/MCF-7 cells xenograft model was established to
      investigate the inhibitory effect of SAHA on tumor growth in vivo. RESULTS: SAHA
      inhibited the proliferation of TAMR/MCF-7 cells in a dose-dependent manner. SAHA
      significantly reduced the expression of HDAC1, 2, 3, 4 and 7 and increased
      acetylated histone H3 and H4. Although SAHA induced G2/M phase arrest of cell
      cycle, apoptotic cell death was very low, which is correlated with the slight
      change in the activation of caspases and PARP cleavage. Interestingly, expression
      of the autophagic cell death markers, LC3-II and beclin-1, was significantly
      increased in TAMR/MCF-7 cells treated with SAHA. Autophagic cell death induced by
      SAHA was confirmed by acridine orange staining and transmission electron
      microscopy (TEM) in TAMR/MCF-7 cells. In mice bearing the TAMR/MCF-7 cell
      xenografts, SAHA significantly reduced the tumor growth and weight, without
      apparent side effects. CONCLUSION: These results suggest that SAHA can induce
      caspase-independent autophagic cell death rather than apoptotic cell death in
      TAMR/MCF-7 cells. SAHA-mediated autophagic cell death is a promising new strategy
      to treatment of tamoxifen-resistant human breast cancer.

PMID- 23155363
TI  - Three-dimensional ultrasound appearance of pelvic floor in nulliparous women and
      pelvic organ prolapse women.
AB  - The present study investigated the morphology and structure of pelvic floor in 50
      nulliparous and 50 pelvic organ prolapse (POP) women using translabial three
      dimensional (3D) ultrasound. The levator hiatus in POP women was significantly
      different from that in nullipara women. In POP women, the size of pelvic floor
      increased, with a circular shape, and the axis of levator hiatus departed from
      the normal position in 36 (72%) cases. The puborectalis was avulsed in 18 (36%)
      cases and the pelvic organs arranged abnormally in 23 (46%) cases. In summary, 3D
      ultrasound is an effective tool to detect the pelvic floor in POP women who
      presented with abnormalities in the morphology and structure of pelvic floor.

PMID- 23155364
TI  - Quantification of BCR-ABL mRNA in plasma/serum of patients with chronic
      myelogenous leukemia.
AB  - Quantification of tumor-associated mRNA extracted from blood cells/tissues
      containing tumor cells is used for evaluation of treatment efficacy or residual
      tumor cell burden in tumors including leukemia. However, this method using tumor
      cell-containing blood/tissue is difficult to evaluate the whole tumor cell burden
      in the body. In order to establish an efficient method to evaluate the whole
      tumor cell burden in the body, we tried to quantify tumor-associated mRNA
      existing in plasma/serum instead of leukemia cell-containing blood cells in
      patients with chronic myelogenous leukemia (CML) and compared the levels of BCR
      ABL mRNA between plasma/serum and peripheral blood cells. mRNA of BCR-ABL, WT1 or
      GAPDH (control molecule) was detected by real-time RT-PCR using RNA extracted
      from plasma/serum of almost all the patients with CML. Copy numbers of BCR-ABL
      mRNA were significantly correlated between plasma/serum and peripheral blood
      cells. However, levels of BCR-ABL mRNA extracted from serum were low compared
      with those extracted with peripheral blood cells. The present findings suggest
      that although real-time RT-PCR of mRNA existing in plasma/serum could be used for
      evaluating the whole tumor cell burden in the body, it's required to establish an
      efficient method to quantify plasma/serum mRNA by nature without degrading during
      the procedure.

PMID- 23155365
TI  - Impact of Trauma on Attenuated Psychotic Symptoms.
AB  - Evidence that trauma may play a role in the development of a psychotic illness
      has lead researchers to investigate the relationship between trauma and the
      content of attenuated psychotic symptoms. Participants in this study were
      considered to be at clinical high risk for developing psychosis by meeting
      criteria for attenuated positive symptom syndrome based on the Structured
      Interview for Prodromal Syndromes. Trained raters used a specifically designed
      codebook to identify content in the vignettes of 45 participants. Various types
      of trauma that had occurred before age 16 were assessed, where participants who
      endorsed more types of trauma were considered to have experienced a greater
      amount of trauma. Spearman rank correlations revealed significant positive
      relationships between increased trauma and feeling watched or followed (rho=0.38,
      p<0.05) and false beliefs of status or power (rho=0.31, p<0.04). Significant
      negative relationships were observed between increased trauma and hearing
      nonnegative voices (rho=-0.39, p<0.01) as well as having unusual negative
      thoughts surrounding the self (rho=-0.31, p<0.05). Although this was a small
      sample, these findings support the possibility of a meaningful relationship
      between experiences of trauma and the content of attenuated positive symptoms.

PMID- 23155366
TI  - Social role patterning in early adulthood in the USA: adolescent predictors and
      concurrent wellbeing across four distinct configurations.
AB  - The decade following secondary school is pivotal in setting the stage for
      adulthood functioning and adjustment. We identify four social role configurations
      of early adults in their mid-20s using latent class analyses in two nationally
      representative samples of American youth in their last year of secondary
      education (modal age 18) who were followed longitudinally into adulthood (age
      25/26). We focus on the big five social role domains of early adulthood:
      education, residential status, employment, cohabitation/marriage, and parenthood.
      Aims were to identify latent classes of social role configurations in early
      adulthood, examine demographic and late adolescent educational predictors of
      these classes, and explore contemporaneous health and adjustment correlates
      focusing on life satisfaction, economic independence, and substance use. Four
      classes with very similar characteristics and prevalence were identified in the
      two cohorts who were born 12 years apart: Educated Students without Children (8%
      in 80s cohort/9% in 90s cohort); Working Singles Living with Parents (16%/18%);
      Educated Workers without Children (45%/46%); and Married Workers with Children
      (31%/27%). Late adolescent demographic and educational variables and mid-20s
      variables were related to class membership. Results evidenced notable
      similarities (and some differences) across cohorts. Discussion focuses on how
      roles facilitate or inhibit each other and the potential diversity of optimal
      patterns of transitions to adulthood.

PMID- 23155367
TI  - Impact of asthma on educational attainment in a socioeconomically deprived
      population: a study linking health, education and social care datasets.
AB  - BACKGROUND: Asthma has the potential to adversely affect children's school
      examination performance, and hence longer term life chances. Asthma morbidity is
      especially high amongst UK ethnic minority children and those experiencing social
      adversity, populations which also have poor educational outcomes. We tested the
      hypothesis that asthma adversely affects performance in national school
      examinations in a large cohort from an area of ethnic diversity and social
      deprivation. METHODS AND FINDINGS: With a novel method (using patient and address
      matching algorithms) we linked administrative and clinical data for 2002-2005 for
      children in east London aged 5-14 years to contemporaneous education and social
      care datasets. We modelled children's performance in school examinations in
      relation to socio-demographic and clinical variables. The dataset captured
      examination performance for 12,136 children who sat at least one national
      examination at Key Stages 1-3. For illustration, estimates are presented as
      percentage changes in Key Stage 2 results. Having asthma was associated with a
      1.1% increase in examination scores (95%CI 0.4 to 1.7)%,p = 0.02. Worse scores
      were associated with Bangladeshi ethnicity -1.3%(-2.5 to -0.1)%,p = 0.03; special
      educational need -14.6%(-15.7 to -13.5)%,p = 0.02; mental health problems -2.5%(
      4.1 to -0.9)%,p = 0.003, and social adversity: living in a smoking household 
      1.2(-1.7 to -0.6)%,p<0.001; living in social housing -0.8%(-1.3 to -0.2)% p =
      0.01, and entitlement to free school meals -0.8%(-1.5 to -0.1)%,p<0.001.
      CONCLUSIONS: Social adversity and ethnicity, but not asthma, are associated with
      poorer performance in national school examinations. Policies to improve
      educational attainment in socially deprived areas should focus on these factors.

PMID- 23155368
TI  - Neural responses to smoking stimuli are influenced by smokers' attitudes towards
      their own smoking behaviour.
AB  - An important feature of addiction is the high drug craving that may promote the
      continuation of consumption. Environmental stimuli classically conditioned to
      drug-intake have a strong motivational power for addicts and can elicit craving.
      However, addicts differ in the attitudes towards their own consumption behavior:
      some are content with drug taking (consonant users) whereas others are discontent
      (dissonant users). Such differences may be important for clinical practice
      because the experience of dissonance might enhance the likelihood to consider
      treatment. This fMRI study investigated in smokers whether these different
      attitudes influence subjective and neural responses to smoking stimuli. Based on
      self-characterization, smokers were divided into consonant and dissonant smokers.
      These two groups were presented smoking stimuli and neutral stimuli. Former
      studies have suggested differences in the impact of smoking stimuli depending on
      the temporal stage of the smoking ritual they are associated with. Therefore, we
      used stimuli associated with the beginning (BEGIN-smoking-stimuli) and stimuli
      associated with the terminal stage (END-smoking-stimuli) of the smoking ritual as
      distinct stimulus categories. Stimulus ratings did not differ between both
      groups. Brain data showed that BEGIN-smoking-stimuli led to enhanced mesolimbic
      responses (amygdala, hippocampus, insula) in dissonant compared to consonant
      smokers. In response to END-smoking-stimuli, dissonant smokers showed reduced
      mesocortical responses (orbitofrontal cortex, subcallosal cortex) compared to
      consonant smokers. These results suggest that smoking stimuli with a high
      incentive value (BEGIN-smoking-stimuli) are more appetitive for dissonant than
      consonant smokers at least on the neural level. To the contrary, smoking stimuli
      with low incentive value (END-smoking-stimuli) seem to be less appetitive for
      dissonant smokers than consonant smokers. These differences might be one reason
      why dissonant smokers experience difficulties in translating their attitudes into
      an actual behavior change.

PMID- 23155369
TI  - Modeling and molecular dynamics of HPA-1a and -1b polymorphisms: effects on the
      structure of the beta3 subunit of the alphaIIbbeta3 integrin.
AB  - BACKGROUND: The HPA-1 alloimmune system carried by the platelet integrin
      alphaIIbbeta3 is the primary cause of alloimmune thrombocytopenia in Caucasians
      and the HPA-1b allele might be a risk factor for thrombosis. HPA-1a and -1b
      alleles are defined by a leucine and a proline, respectively, at position 33 in
      the beta3 subunit. Although the structure of alphaIIbbeta3 is available, little
      is known about structural effects of the L33P substitution and its consequences
      on immune response and integrin functions. METHODOLOGY/PRINCIPAL FINDINGS: A
      complete 3D model of the L33-beta3 extracellular domain was built and a P33 model
      was obtained by in silico mutagenesis. We then performed molecular dynamics
      simulations. Analyses focused on the PSI, I-EGF-1, and I-EGF-2 domains and
      confirmed higher exposure of residue 33 in the L33 beta3 form. These analyses
      also showed major structural flexibility of all three domains in both forms, but
      increased flexibility in the P33 beta3 form. The L33P substitution does not alter
      the local structure (residues 33 to 35) of the PSI domain, but modifies the
      structural equilibrium of the three domains. CONCLUSIONS: These results provide a
      better understanding of HPA-1 epitopes complexity and alloimmunization prevalence
      of HPA-1a. P33 gain of structure flexibility in the beta3 knee may explain the
      increased adhesion capacity of HPA-1b platelets and the associated thrombotic
      risk. Our study provides important new insights into the relationship between HPA
      1 variants and beta3 structure that suggest possible effects on the alloimmune
      response and platelet function.

PMID- 23155370
TI  - Skeletogenic fate of zebrafish cranial and trunk neural crest.
AB  - The neural crest (NC) is a major contributor to the vertebrate craniofacial
      skeleton, detailed in model organisms through embryological and genetic
      approaches, most notably in chick and mouse. Despite many similarities between
      these rather distant species, there are also distinct differences in the
      contribution of the NC, particularly to the calvariae of the skull. Lack of
      information about other vertebrate groups precludes an understanding of the
      evolutionary significance of these differences. Study of zebrafish craniofacial
      development has contributed substantially to understanding of cartilage and bone
      formation in teleosts, but there is currently little information on NC
      contribution to the zebrafish skeleton. Here, we employ a two-transgene system
      based on Cre recombinase to genetically label NC in the zebrafish. We demonstrate
      NC contribution to cells in the cranial ganglia and peripheral nervous system
      known to be NC-derived, as well as to a subset of myocardial cells. The indelible
      labeling also enables us to determine NC contribution to late-forming bones,
      including the calvariae. We confirm suspected NC origin of cartilage and bones of
      the viscerocranium, including cartilages such as the hyosymplectic and its
      replacement bones (hymandibula and symplectic) and membranous bones such as the
      opercle. The cleithrum develops at the border of NC and mesoderm, and as an
      ancestral component of the pectoral girdle was predicted to be a hybrid bone
      composed of both NC and mesoderm tissues. However, we find no evidence of a NC
      contribution to the cleithrum. Similarly, in the vault of the skull, the parietal
      bones and the caudal portion of the frontal bones show no evidence of NC
      contribution. We also determine a NC origin for caudal fin lepidotrichia; the
      presumption is that these are derived from trunk NC, demonstrating that these
      cells have the ability to form bone during normal vertebrate development.

PMID- 23155371
TI  - Inferences from the historical distribution of wild and domesticated maize
      provide ecological and evolutionary insight.
AB  - BACKGROUND: The species Zea mays includes both domesticated maize (ssp. mays) and
      its closest wild relatives known as the teosintes. While genetic and
      archaeological studies have provided a well-established history of Z. mays
      evolution, there is currently minimal description of its current and past
      distribution. Here, we implemented species distribution modeling using
      paleoclimatic models of the last interglacial (LI; ~135,000 BP) and the last
      glacial maximum (LGM; ~21,000 BP) to hindcast the distribution of Zea mays
      subspecies over time and to revisit current knowledge of its phylogeography and
      evolutionary history. METHODOLOGY/PRINCIPAL FINDINGS: Using a large occurrence
      data set and the distribution modeling MaxEnt algorithm, we obtained robust
      present and past species distributions of the two widely distributed teosinte
      subspecies (ssps. parviglumis and mexicana) revealing almost perfect
      complementarity, stable through time, of their occupied distributions. We also
      investigated the present distributions of primitive maize landraces, which
      overlapped but were broader than those of the teosintes. Our data reinforced the
      idea that little historical gene flow has occurred between teosinte subspecies,
      but maize has served as a genetic bridge between them. We observed an expansion
      of teosinte habitat from the LI, consistent with population genetic data.
      Finally, we identified locations potentially serving as refugia for the teosintes
      throughout epochs of climate change and sites that should be targeted in future
      collections. CONCLUSION/SIGNIFICANCE: The restricted and highly contrasting
      ecological niches of the wild teosintes differ substantially from domesticated
      maize. Variables determining the distributions of these taxa can inform future
      considerations of local adaptation and the impacts of climate change. Our
      assessment of the changing distributions of Zea mays taxa over time offers a
      unique glimpse into the history of maize, highlighting a strategy for the study
      of domestication that may prove useful for other species.

PMID- 23155372
TI  - Mimicking insect communication: release and detection of pheromone,
      biosynthesized by an alcohol acetyl transferase immobilized in a microreactor.
AB  - Infochemical production, release and detection of (Z,E)-9,11-tetradecadienyl
      acetate, the major component of the pheromone of the moth Spodoptera littoralis,
      is achieved in a novel microfluidic system designed to mimic the final step of
      the pheromone biosynthesis by immobilized recombinant alcohol acetyl transferase.
      The microfluidic system is part of an "artificial gland", i.e., a chemoemitter
      that comprises a microreactor connected to a microevaporator and is able to
      produce and release a pre-defined amount of the major component of the pheromone
      from the corresponding (Z,E)-9,11-tetradecadienol. Performance of the entire
      chemoemitter has been assessed in electrophysiological and behavioral
      experiments. Electroantennographic depolarizations of the pheromone produced by
      the chemoemitter were ca. 40% relative to that evoked by the synthetic pheromone.
      In a wind tunnel, the pheromone released from the evaporator elicited on males a
      similar attraction behavior as 3 virgin females in most of the parameters
      considered.

PMID- 23155373
TI  - Programmable in vivo selection of arbitrary DNA sequences.
AB  - The extraordinary fidelity, sensory and regulatory capacity of natural
      intracellular machinery is generally confined to their endogenous environment.
      Nevertheless, synthetic bio-molecular components have been engineered to
      interface with the cellular transcription, splicing and translation machinery in
      vivo by embedding functional features such as promoters, introns and ribosome
      binding sites, respectively, into their design. Tapping and directing the power
      of intracellular molecular processing towards synthetic bio-molecular inputs is
      potentially a powerful approach, albeit limited by our ability to streamline the
      interface of synthetic components with the intracellular machinery in vivo. Here
      we show how a library of synthetic DNA devices, each bearing an input DNA
      sequence and a logical selection module, can be designed to direct its own
      probing and processing by interfacing with the bacterial DNA mismatch repair
      (MMR) system in vivo and selecting for the most abundant variant, regardless of
      its function. The device provides proof of concept for programmable, function
      independent DNA selection in vivo and provides a unique example of a logical
      functional interface of an engineered synthetic component with a complex
      endogenous cellular system. Further research into the design, construction and
      operation of synthetic devices in vivo may lead to other functional devices that
      interface with other complex cellular processes for both research and applied
      purposes.

PMID- 23155374
TI  - Antibody to Epstein-Barr virus deoxyuridine triphosphate nucleotidohydrolase and
      deoxyribonucleotide polymerase in a chronic fatigue syndrome subset.
AB  - BACKGROUND: A defined diagnostic panel differentiated patients who had been
      diagnosed with chronic fatigue syndrome (CFS), based upon Fukuda/Carruthers
      criteria. This diagnostic panel identified an Epstein-Barr virus (EBV) subset of
      patients (6), excluding for the first time other similar "clinical" conditions
      such as cytomegalovirus (CMV), human herpesvirus 6 (HHV6), babesiosis,
      ehrlichiosis, borreliosis, Mycoplasma pneumoniae, Chlamydia pneumoniae, and adult
      rheumatic fever, which may be mistakenly called CFS. CFS patients were treated
      with valacyclovir (14.3 mg/kg q6h) for >= 12 months. Each patient improved, based
      upon the Functional Activity Appraisal: Energy Index Score Healthcare Worker
      Assessment (EIPS), which is a validated (FSS-9), item scale with high degree of
      internal consistency measured by Cronbach's alpha. METHODS: Antibody to EBV viral
      capsid antigen (VCA) IgM, EBV Diffuse Early Antigen EA(D), and neutralizing
      antibodies against EBV-encoded DNA polymerase and EBV-encoded dUTPase were
      assayed serially approximately every three months for 13-16 months from sera
      obtained from patients with CFS (6) and from sera obtained from twenty patients
      who had no history of CFS. RESULTS: Antibodies to EBV EA(D) and neutralizing
      antibodies against the encoded-proteins EBV DNA polymerase and deoxyuridine
      triphosphate nucleotidohydrolase (dUTPase) were present in the EBV subset CFS
      patients. Of the sera samples obtained from patients with CFS 93.9% were positive
      for EA(D), while 31.6% of the control patients were positive for EBV EA(D). Serum
      samples were positive for neutralizing antibodies against the EBV-encoded dUTPase
      (23/52; 44.2%) and DNA polymerase (41/52; 78.8%) in EBV subset CFS patients, but
      negative in sera of controls. CONCLUSIONS: There is prolonged elevated antibody
      level against the encoded proteins EBV dUTPase and EBV DNA polymerase in a subset
      of CFS patients, suggesting that this antibody panel could be used to identify
      these patients, if these preliminary findings are corroborated by studies with a
      larger number of EBV subset CFS patients.

PMID- 23155375
TI  - The mobilization and recruitment of c-kit+ cells contribute to wound healing
      after surgery.
AB  - Delayed wound healing is a serious clinical problem in patients after surgery. A
      recent study has demonstrated that bone marrow-derived c-kit-positive (c-kit(+))
      cells play important roles in repairing and regenerating various tissues and
      organs. To examine the hypothesis that surgical injury induces the mobilization
      and recruitment of c-kit+ cells to accelerate wound healing. Mice were subjected
      to a left pneumonectomy. The mobilization of c-kit+ cells was monitored after
      surgery. Using green fluorescent protein (GFP(+)) bone marrow-transplanted
      chimera mice, we investigated further whether the mobilized c-kit+ cells were
      recruited to effect wound healing in a skin puncture model. The group with left
      pneumonectomies increased the c-kit(+) and CD34(+) stem cells in peripheral blood
      24 h after surgery. At 3 days after surgery, the skin wound size was observed to
      be significantly smaller, and the number of bone marrow-derived GFP(+) cells and
      GFP(+)/c-kit+ cells in the wound tissue was significantly greater in mice that
      had received pneumonectomies, as compared with those that had received a sham
      operation. Furthermore, some of these GFP(+) cells were positively expressed
      specific markers of macrophages (F4/80), endothelial cells (CD31), and
      myofibroblasts (alphaSMA). The administration of AMD3100, an antagonist of a
      stromal-cell derived factor (SDF)-1/CXCR4 signaling pathway, reduced the number
      of GFP(+) cells in wound tissue and completely negated the accelerated wound
      healing. Surgical injury induces the mobilization and recruitment of c-kit+ cells
      to contribute to wound healing. Regulating c-kit+ cells may provide a new
      approach that accelerates wound healing after surgery.

PMID- 23155376
TI  - Bacterial colony from two-dimensional division to three-dimensional development.
AB  - On agar surface, bacterial daughter cells form a 4-cell array after the first two
      rounds of division, and this phenomenon has been previously attributed to a
      balancing of interactions among the daughter bacteria and the underneath agar. We
      studied further the organization and development of colony after additional
      generations. By confocal laser scanning microscopy and real-time imaging, we
      observed that bacterial cells were able to self-organize and resulted in a near
      circular micro-colony consisting of monolayer cells. After continuous dividing,
      bacteria transited from two-dimensional expansion into three-dimensional growth
      and formed two to multi-layers in the center but retained a monolayer in the
      outer ring of the circular colony. The transverse width of this outer ring
      appeared to be approximately constant once the micro-colony reached a certain
      age. This observation supports the notion that balanced interplays of the forces
      involved lead to a gross morphology as the bacteria divide into offspring on agar
      surface. In this case, the result is due to a balance between the expansion force
      of the dividing bacteria, the non-covalent force among bacterial offspring and
      that between bacteria and substratum.

PMID- 23155377
TI  - A remarkable case of micro-endemism in Laonastes aenigmamus (Diatomyidae,
      Rodentia) revealed by nuclear and mitochondrial DNA sequence data.
AB  - L. aenigmamus is endemic to the limestone formations of the Khammuan Province
      (Lao PDR), and is strongly specialized ecologically. From the survey of 137
      individuals collected from 38 localities, we studied the phylogeography of this
      species using one mitochondrial (Cyt b) and two nuclear genes (BFIBR and GHR).
      Cyt b analyses reveal a strong mtDNA phylogeographical structure: 8 major
      geographical clades differing by 5-14% sequence divergence were identified, most
      of them corresponding to distinct karst areas. Nuclear markers display congruent
      results but with a less genetic structuring. Together, the data strongly suggest
      an inland insular model for Laonastes population structure. With 8 to 16
      evolutionary significant units in a small area (about 200*50 km) this represents
      an exceptional example of micro-endemism. Our results suggest that L. aenigmamus
      may represent a complex of species and/or sub-species. The common ancestor of all
      Laonastes may have been widely distributed within the limestone formations of the
      Khammuan Province at the end of Miocene/beginning of the Pliocene. Parallel
      events of karst fragmentation and population isolation would have occurred during
      the Pleistocene or/and the end of the Pliocene. The limited gene flow detected
      between populations from different karst blocks restrains the likelihood of
      survival of Laonastes. This work increases the necessity for a strict protection
      of this rare animal and its habitat and provides exclusive information, essential
      to the organization of its protection.

PMID- 23155378
TI  - Bats in a farming landscape benefit from linear remnants and unimproved pastures.
AB  - Schemes designed to make farming landscapes less hostile to wildlife have been
      questioned because target taxa do not always respond in the expected manner.
      Microbats are often overlooked in this process, yet persist in agricultural
      landscapes and exert top-down control of crop pests. We investigated the
      relationship between microbats and measures commonly incorporated into agri
      environment schemes, to derive management recommendations for their ongoing
      conservation. We used acoustic detectors to quantify bat species richness,
      activity, and feeding in 32 linear remnants and adjacent fields across an
      agricultural region of New South Wales, Australia. Nocturnal arthropods were
      simultaneously trapped using black-light traps. We recorded 91,969 bat calls,
      17,277 of which could be attributed to one of the 13 taxa recorded, and 491 calls
      contained feeding buzzes. The linear remnants supported higher bat activity than
      the fields, but species richness and feeding activity did not significantly
      differ. We trapped a mean 87.6 g (+/-17.6 g SE) of arthropods per night, but
      found no differences in biomass between land uses. Wider linear remnants with
      intact native vegetation supported more bat species, as did those adjacent to
      unsealed, as opposed to sealed roads. Fields of unimproved native pastures, with
      more retained scattered trees and associated hollows and logs, supported the
      greatest bat species richness and activity. We conclude that the juxtaposition of
      linear remnants of intact vegetation and scattered trees in fields, coupled with
      less-intensive land uses such as unimproved pastures will benefit bat communities
      in agricultural landscapes, and should be incorporated into agri-environment
      schemes. In contrast, sealed roads may act as a deterrent. The "wildlife friendly
      farming" vs "land sparing" debate has so far primarily focussed on birds, but
      here we have found evidence that the integration of both approaches could
      particularly benefit bats.

PMID- 23155379
TI  - Phylogeny and evolutionary patterns in the Dwarf crayfish subfamily (Decapoda:
      Cambarellinae).
AB  - The Dwarf crayfish or Cambarellinae, is a morphologically singular subfamily of
      decapod crustaceans that contains only one genus, Cambarellus. Its intriguing
      distribution, along the river basins of the Gulf Coast of United States (Gulf
      Group) and into Central Mexico (Mexican Group), has until now lacked of
      satisfactory explanation. This study provides a comprehensive sampling of most of
      the extant species of Cambarellus and sheds light on its evolutionary history,
      systematics and biogeography. We tested the impact of Gulf Group versus Mexican
      Group geography on rates of cladogenesis using a maximum likelihood framework,
      testing different models of birth/extinction of lineages. We propose a
      comprehensive phylogenetic hypothesis for the subfamily based on mitochondrial
      and nuclear loci (3,833 bp) using Bayesian and Maximum Likelihood methods. The
      phylogenetic structure found two phylogenetic groups associated to the two main
      geographic components (Gulf Group and Mexican Group) and is partially consistent
      with the historical structure of river basins. The previous hypothesis, which
      divided the genus into three subgenera based on genitalia morphology was only
      partially supported (P = 0.047), resulting in a paraphyletic subgenus
      Pandicambarus. We found at least two cases in which phylogenetic structure failed
      to recover monophyly of recognized species while detecting several cases of
      cryptic diversity, corresponding to lineages not assigned to any described
      species. Cladogenetic patterns in the entire subfamily are better explained by an
      allopatric model of speciation. Diversification analyses showed similar
      cladogenesis patterns between both groups and did not significantly differ from
      the constant rate models. While cladogenesis in the Gulf Group is coincident in
      time with changes in the sea levels, in the Mexican Group, cladogenesis is
      congruent with the formation of the Trans-Mexican Volcanic Belt. Our results show
      how similar allopatric divergence in freshwater organisms can be promoted through
      diverse vicariant factors.

PMID- 23155380
TI  - Different regional gray matter loss in recent onset PTSD and non PTSD after a
      single prolonged trauma exposure.
AB  - OBJECTIVE: Gray matter loss in the limbic structures was found in recent onset
      post traumatic stress disorder (PTSD) patients. In the present study, we measured
      regional gray matter volume in trauma survivors to verify the hypothesis that
      stress may cause different regional gray matter loss in trauma survivors with and
      without recent onset PTSD. METHOD: High resolution T1-weighted magnetic resonance
      imaging (MRI) were obtained from coal mine flood disaster survivors with (n = 10)
      and without (n = 10) recent onset PTSD and 20 no trauma exposed normal controls.
      The voxel-based morphometry (VBM) method was used to measure the regional gray
      matter volume in three groups, the correlations of PTSD symptom severities with
      the gray matter volume in trauma survivors were also analyzed by multiple
      regression. RESULTS: Compared with normal controls, recent onset PTSD patients
      had smaller gray matter volume in left dorsal anterior cingulate cortex (ACC),
      and non PTSD subjects had smaller gray matter volume in the right pulvinar and
      left pallidum. The gray matter volume of the trauma survivors correlated
      negatively with CAPS scores in the right frontal lobe, left anterior and middle
      cingulate cortex, bilateral cuneus cortex, right middle occipital lobe, while in
      the recent onset PTSD, the gray matter volume correlated negatively with CAPS
      scores in bilateral superior medial frontal lobe and right ACC. CONCLUSION: The
      present study identified gray matter loss in different regions in recent onset
      PTSD and non PTSD after a single prolonged trauma exposure. The gray matter
      volume of left dorsal ACC associated with the development of PTSD, while the gray
      matter volume of right pulvinar and left pallidum associated with the response to
      the severe stress. The atrophy of the frontal and limbic cortices predicts the
      symptom severities of the PTSD.

PMID- 23155381
TI  - Transforming growth factor alpha (TGFalpha) regulates granulosa cell tumor (GCT)
      cell proliferation and migration through activation of multiple pathways.
AB  - Granulosa cell tumors (GCTs) are the most common ovarian estrogen producing
      tumors, leading to symptoms of excessive estrogen such as endometrial hyperplasia
      and endometrial adenocarcinoma. These tumors have malignant potential and often
      recur. The etiology of GCT is unknown. TGFalpha is a potent mitogen for many
      different cells. However, its function in GCT initiation, progression and
      metastasis has not been determined. The present study aims to determine whether
      TGFalpha plays a role in the growth of GCT cells. KGN cells, which are derived
      from an invasive GCT and have many features of normal granulosa cells, were used
      as the cellular model. Immunohistochemistry, Western blot and RT-PCR results
      showed that the ErbB family of receptors is expressed in human GCT tissues and
      GCT cell lines. RT-PCR results also indicated that TGFalpha and EGF are expressed
      in the human granulosa cells and the GCT cell lines, suggesting that TGFalpha
      might regulate GCT cell function in an autocrine/paracrine manner. TGFalpha
      stimulated KGN cell DNA synthesis, cell proliferation, cell viability, cell cycle
      progression, and cell migration. TGFalpha rapidly activated EGFR/PI3K/Akt and
      mTOR pathways, as indicated by rapid phosphorylation of Akt, TSC2, Rictor, mTOR,
      P70S6K and S6 proteins following TGFalpha treatment. TGFalpha also rapidly
      activated the EGFR/MEK/ERK pathway, and P38 MAPK pathways, as indicated by the
      rapid phosphorylation of EGFR, MEK, ERK1/2, P38, and CREB after TGFalpha
      treatment. Whereas TGFalpha triggered a transient activation of Akt, it induced a
      sustained activation of ERK1/2 in KGN cells. Long-term treatment of KGN cells
      with TGFalpha resulted in a significant increase in cyclin D2 and a decrease in
      p27/Kip1, two critical regulators of granulosa cell proliferation and granulosa
      cell tumorigenesis. In conclusion, TGFalpha, via multiple signaling pathways,
      regulates KGN cell proliferation and migration and may play an important role in
      the growth and metastasis of GCTs.

PMID- 23155383
TI  - Using co-occurrence to evaluate belief coherence in a large non clinical sample.
AB  - Much of the recent neuropsychological literature on false beliefs (delusions) has
      tended to focus on individual or single beliefs, with few studies actually
      investigating the relationship or co-occurrence between different types of co
      existing beliefs. Quine and Ullian proposed the hypothesis that our beliefs form
      an interconnected web in which the beliefs that make up that system must somehow
      "cohere" with one another and avoid cognitive dissonance. As such beliefs are
      unlikely to be encapsulated (i.e., exist in isolation from other beliefs). The
      aim of this preliminary study was to empirically evaluate the probability of
      belief co-occurrence as one indicator of coherence in a large sample of subjects
      involving three different thematic sets of beliefs (delusion-like, paranormal &
      religious, and societal/cultural). Results showed that the degree of belief co
      endorsement between beliefs within thematic groupings was greater than random
      occurrence, lending support to Quine and Ullian's coherentist account. Some
      associations, however, were relatively weak, providing for well-established
      examples of cognitive dissonance.

PMID- 23155382
TI  - Direct angiotensin II type 2 receptor stimulation ameliorates insulin resistance
      in type 2 diabetes mice with PPARgamma activation.
AB  - OBJECTIVES: The role of angiotensin II type 2 (AT(2)) receptor stimulation in the
      pathogenesis of insulin resistance is still unclear. Therefore we examined the
      possibility that direct AT(2) receptor stimulation by compound 21 (C21) might
      contribute to possible insulin-sensitizing/anti-diabetic effects in type 2
      diabetes (T2DM) with PPARgamma activation, mainly focusing on adipose tissue.
      METHODS: T2DM mice, KK-Ay, were subjected to intraperitoneal injection of C21
      and/or a PPARgamma antagonist, GW9662 in drinking water for 2 weeks. Insulin
      resistance was evaluated by oral glucose tolerance test, insulin tolerance test,
      and uptake of 2-[(3)H] deoxy-D-glucose in white adipose tissue. Morphological
      changes of adipose tissues as well as adipocyte differentiation and inflammatory
      response were examined. RESULTS: Treatment with C21 ameliorated insulin
      resistance in KK-Ay mice without influencing blood pressure, at least partially
      through effects on the PPARgamma pathway. C21 treatment increased serum
      adiponectin concentration and decreased TNF-alpha concentration; however, these
      effects were attenuated by PPARgamma blockade by co-treatment with GW9662.
      Moreover, we observed that administration of C21 enhanced adipocyte
      differentiation and PPARgamma DNA-binding activity, with a decrease in
      inflammation in white adipose tissue, whereas these effects of C21 were
      attenuated by co-treatment with GW9662. We also observed that administration of
      C21 restored beta cell damage in diabetic pancreatic tissue. CONCLUSION: The
      present study demonstrated that direct AT(2) receptor stimulation by C21
      accompanied with PPARgamma activation ameliorated insulin resistance in T2DM
      mice, at least partially due to improvement of adipocyte dysfunction and
      protection of pancreatic beta cells.

PMID- 23155384
TI  - Antibodies against Marinobacter algicola and Salmonella typhimurium flagellins do
      not cross-neutralize TLR5 activation.
AB  - Flagellins evoke strong innate and adaptive immune responses. These proteins may
      play a key role as radioprotectors, exert antitumoral activity in certain types
      of tumor and reduce graft-versus-host disease in allogeneic hematopoietic stem
      cell transplant recipients. Notwithstanding, flagellins are highly immunogenic,
      and repeated use leads to their neutralization by systemic antibodies. This
      neutralization is not prevented by using functional deleted flagellins. These
      observations led us to explore the possibility of preventing initial
      neutralization by means of another functional flagellin that does not belong to
      common pathogenic bacteria but that has the capacity to activate TLR5. Here we
      characterized the functional capacity of the two-phase Marinobacter algicola (MA)
      derived flagellins (F and FR) as systemic and mucosal adjuvants and compared
      their performance with that of Salmonella typhimurium (STF) flagellins (FljB and
      FliC). We also report for the first time on the in vitro and in vivo capacity of
      various flagellins to trigger TLR5 activation in the presence of species-specific
      anti-flagellin antibodies, the cross-neutralization mediated by these antibodies,
      and the sequential use of these flagellins for TLR5 activation. Our results
      showed that MA flagellins behave in a similar way to STF ones, inducing pro
      inflammatory cytokines (IL8, CCL20, CCL2) and evoking a strong in vivo antibody
      response against a model epitope. More importantly, MA flagellins were fully
      functional, in vitro or in vivo, in the presence of a high concentration of
      neutralizing anti-flagellin STF antibodies, and STF flagellin was not inhibited
      by neutralizing anti-flagellin MA antibodies. The use of active flagellins from
      distinct bacteria could be a useful approach to prevent systemic neutralization
      of this group of adjuvants and to facilitate the rational design of flagellin
      based vaccines and/or other therapeutic treatments (against ischemia, acute renal
      failure, tumors, ionizing radiations and also to improve the outcome of bone
      marrow transplants).

PMID- 23155385
TI  - Definition of the sigma(W) regulon of Bacillus subtilis in the absence of stress.
AB  - Bacteria employ extracytoplasmic function (ECF) sigma factors for their responses
      to environmental stresses. Despite intensive research, the molecular dissection
      of ECF sigma factor regulons has remained a major challenge due to overlaps in
      the ECF sigma factor-regulated genes and the stimuli that activate the different
      ECF sigma factors. Here we have employed tiling arrays to single out the ECF
      sigma(W) regulon of the Gram-positive bacterium Bacillus subtilis from the
      overlapping ECF sigma(X), sigma(Y), and sigma(M) regulons. For this purpose, we
      profiled the transcriptome of a B. subtilis sigW mutant under non-stress
      conditions to select candidate genes that are strictly sigma(W)-regulated. Under
      these conditions, sigma(W) exhibits a basal level of activity. Subsequently, we
      verified the sigma(W)-dependency of candidate genes by comparing their transcript
      profiles to transcriptome data obtained with the parental B. subtilis strain 168
      grown under 104 different conditions, including relevant stress conditions, such
      as salt shock. In addition, we investigated the transcriptomes of rasP or prsW
      mutant strains that lack the proteases involved in the degradation of the
      sigma(W) anti-sigma factor RsiW and subsequent activation of the sigma(W)
      regulon. Taken together, our studies identify 89 genes as being strictly sigma(W)
      regulated, including several genes for non-coding RNAs. The effects of rasP or
      prsW mutations on the expression of sigma(W)-dependent genes were relatively
      mild, which implies that sigma(W)-dependent transcription under non-stress
      conditions is not strictly related to RasP and PrsW. Lastly, we show that the
      pleiotropic phenotype of rasP mutant cells, which have defects in competence
      development, protein secretion and membrane protein production, is not mirrored
      in the transcript profile of these cells. This implies that RasP is not only
      important for transcriptional regulation via sigma(W), but that this membrane
      protease also exerts other important post-transcriptional regulatory functions.

PMID- 23155386
TI  - Biological effects of cigarette smoke in cultured human retinal pigment
      epithelial cells.
AB  - The goal of the present study was to determine whether treatment with cigarette
      smoke extract (CSE) induces cell loss, cellular senescence, and extracellular
      matrix (ECM) synthesis in primary human retinal pigment epithelial (RPE) cells.
      Primary cultured human RPE cells were exposed to 2, 4, 8, and 12% of CSE
      concentration for 24 hours. Cell loss was detected by cell viability assay. Lipid
      peroxidation was assessed by loss of cis-parinaric acid (PNA) fluorescence.
      Senescence-associated beta-galactosidase (SA-beta-Gal) activity was detected by
      histochemical staining. Expression of apolipoprotein J (Apo J), connective tissue
      growth factor (CTGF), fibronectin, and laminin were examined by real-time PCR,
      western blot, or ELISA experiments. The results showed that exposure of cells to
      12% of CSE concentration induced cell death, while treatment of cells with 2, 4,
      and 8% CSE increased lipid peroxidation. Exposure to 8% of CSE markedly increased
      the number of SA-beta-Gal positive cells to up to 82%, and the mRNA expression of
      Apo J, CTGF, and fibronectin by approximately 3-4 fold. Treatment with 8% of CSE
      also increased the protein expression of Apo J and CTGF and the secretion of
      fibronectin and laminin. Thus, treatment with CSE can induce cell loss, senescent
      changes, and ECM synthesis in primary human RPE cells. It may be speculated that
      cigarette smoke could be involved in cellular events in RPE cells as seen in age
      related macular degeneration.

PMID- 23155387
TI  - Equivalence of self- and staff-collected nasal swabs for the detection of viral
      respiratory pathogens.
AB  - BACKGROUND: The need for the timely collection of diagnostic biosamples during
      symptomatic episodes represents a major obstacle to large-scale studies on acute
      respiratory infection (ARI) epidemiology. This may be circumvented by having the
      participants collect their own nasal swabs. We compared self- and staff-collected
      swabs in terms of swabbing quality and detection of viral respiratory pathogens.
      METHODOLOGY/PRINCIPAL FINDINGS: We conducted a prospective study among employees
      of our institution during the ARI season 2010/2011 (December-March). Weekly
      emails were sent to the participants (n = 84), reminding them to come to the
      study center in case of new symptoms. The participants self-collected an anterior
      nasal swab from one nostril, and trained study personnel collected one from the
      other nostril. The participants self-collected another two swabs (one from each
      nostril) on a subsequent day. Human beta-actin DNA concentration was determined
      in the swabs as a quality control. Viral respiratory pathogens were detected by
      multiplex RT-PCR (Seeplex RV15 kit, Seegene, Eschborn, Germany). Of 84
      participants, 56 (67%) reported at least one ARI episode, 18 participants two,
      and one participant three. Self-swabbing was highly accepted by the participants.
      The amount of beta-actin DNA per swab was higher in the self- than in the staff
      collected swabs (p = 0.008). beta-actin concentration was lower in the self-swabs
      collected on day 1 than in those collected on a subsequent day (p<0.0001). A
      respiratory viral pathogen was detected in 31% (23/75) of staff- and in 35%
      (26/75) of self-collected swabs (p = 0.36). With both approaches, the most
      frequently identified pathogens were human rhinoviruses A/B/C (12/75 swabs, 16%)
      and human coronavirus OC43 (4/75 swabs, 5%). There was almost perfect agreement
      between self- and staff-collected swabs in terms of pathogen detection (agreement
      = 93%, kappa = 0.85, p<0.0001). CONCLUSIONS/SIGNIFICANCE: Nasal self-swabbing for
      identification of viral ARI pathogens proved to be equivalent to staff-swabbing
      in this population in terms of acceptance and pathogen detection.

PMID- 23155388
TI  - Multi-color single particle tracking with quantum dots.
AB  - Quantum dots (QDs) have long promised to revolutionize fluorescence detection to
      include even applications requiring simultaneous multi-species detection at
      single molecule sensitivity. Despite the early promise, the unique optical
      properties of QDs have not yet been fully exploited in e. g. multiplex single
      molecule sensitivity applications such as single particle tracking (SPT). In
      order to fully optimize single molecule multiplex application with QDs, we have
      in this work performed a comprehensive quantitative investigation of the
      fluorescence intensities, fluorescence intensity fluctuations, and hydrodynamic
      radii of eight types of commercially available water soluble QDs. In this study,
      we show that the fluorescence intensity of CdSe core QDs increases as the
      emission of the QDs shifts towards the red but that hybrid CdSe/CdTe core QDs are
      less bright than the furthest red-shifted CdSe QDs. We further show that there is
      only a small size advantage in using blue-shifted QDs in biological applications
      because of the additional size of the water-stabilizing surface coat. Extending
      previous work, we finally also show that parallel four color multicolor (MC)-SPT
      with QDs is possible at an image acquisition rate of at least 25 Hz. We
      demonstrate the technique by measuring the lateral dynamics of a lipid, biotin
      cap-DPPE, in the cellular plasma membrane of live cells using four different
      colors of QDs; QD565, QD605, QD655, and QD705 as labels.

PMID- 23155389
TI  - Not all offspring are created equal: variation in larval characteristics in a
      serially spawning damselfish.
AB  - The way organisms allocate their resources to growth and reproduction are key
      attributes differentiating life histories. Many organisms spawn multiple times in
      a breeding season, but few studies have investigated the impact of serial
      spawning on reproductive allocation. This study investigated whether resource
      allocation was influenced by parental characteristics and prior spawning history
      in a serial spawning tropical damselfish (Pomacentrus amboinensis). The offspring
      attributes of isolated parents of known characteristics were monitored over a 6
      week breeding period in the field. Smaller females produced larvae of longer
      length and larger energy reserves at hatching. This finding is contrary to
      several other studies that found larger females produce offspring of greater
      quality. We found that resource allocation in the form of reproductive output was
      not influenced by the number of spawning events within the breeding season, with
      larger females producing the greatest number of offspring. Larval characteristics
      changed as spawning progressed. There was a general decline in length of larvae
      produced, with an increase in the size of the larval yolk-sac, for all females
      regardless of size as spawning progressed. This trend was accentuated by the
      smallest females. This change in larval characteristics may reflect a parental
      ability to forecast unfavourable conditions as the season progresses or a
      mechanism to ensure that some will survive no matter what conditions they
      encounter. This study highlights the importance of accounting for temporal
      changes in reproductive allocation in studies of reproductive trade-offs and
      investigations into the importance of parental effects.

PMID- 23155390
TI  - Racial bias in perceptions of others' pain.
AB  - The present work provides evidence that people assume a priori that Blacks feel
      less pain than do Whites. It also demonstrates that this bias is rooted in
      perceptions of status and the privilege (or hardship) status confers, not race
      per se. Archival data from the National Football League injury reports reveal
      that, relative to injured White players, injured Black players are deemed more
      likely to play in a subsequent game, possibly because people assume they feel
      less pain. Experiments 1-4 show that White and Black Americans-including
      registered nurses and nursing students-assume that Black people feel less pain
      than do White people. Finally, Experiments 5 and 6 provide evidence that this
      bias is rooted in perceptions of status, not race per se. Taken together, these
      data have important implications for understanding race-related biases and
      healthcare disparities.

PMID- 23155391
TI  - Dysplasia-carcinoma transition specific transcripts in colonic biopsy samples.
AB  - BACKGROUND: The early molecular detection of the dysplasia-carcinoma transition
      may enhance the strength of diagnosis in the case of colonic biopsies. Our aims
      were to identify characteristic transcript sets in order to develop diagnostic
      mRNA expression patterns for objective classification of benign and malignant
      colorectal diseases and to test the classificatory power of these markers on an
      independent sample set. METHODOLOGY/PRINCIPAL FINDINGS: Colorectal cancer (CRC)
      and adenoma specific transcript sets were identified using HGU133plus2
      microarrays and 53 biopsies (22 CRC, 20 adenoma and 11 normal). Ninety-four
      independent biopsies (27 CRC, 29 adenoma and 38 normal) were analyzed on
      microarrays for testing the classificatory power of the discriminatory genes.
      Array real-time PCR validation was done on 68 independent samples (24 CRC, 24
      adenoma and 20 normal). A set of 11 transcripts (including CXCL1, CHI3L1 and
      GREM1) was determined which could correctly discriminate between high-grade
      dysplastic adenoma and CRC samples by 100% sensitivity and 88.9% specificity. The
      discriminatory power of the marker set was proved to be high on independent
      samples in both microarray and RT-PCR analyses. 95.6% of original and 94.1% of
      cross-validated samples was correctly classified in discriminant analysis.
      CONCLUSIONS/SIGNIFICANCE: The identified transcripts could correctly characterize
      the dysplasia-carcinoma transition in biopsy samples, also on a large independent
      sample set. These markers can establish the basis of gene expression based
      diagnostic classification of colorectal cancer. Diagnostic RT-PCR cards can
      become part of the automated routine procedure.

PMID- 23155392
TI  - RAD001 enhances the potency of BEZ235 to inhibit mTOR signaling and tumor growth.
AB  - The mammalian target of rapamycin (mTOR) is regulated by oncogenic growth factor
      signals and plays a pivotal role in controlling cellular metabolism, growth and
      survival. Everolimus (RAD001) is an allosteric mTOR inhibitor that has shown
      marked efficacy in certain cancers but is unable to completely inhibit mTOR
      activity. ATP-competitive mTOR inhibitors such as NVP-BEZ235 can block rapamycin
      insensitive mTOR readouts and have entered clinical development as anti-cancer
      agents. Here, we show the degree to which RAD001 and BEZ235 can be
      synergistically combined to inhibit mTOR pathway activation, cell proliferation
      and tumor growth, both in vitro and in vivo. RAD001 and BEZ235 synergized in
      cancer lines representing different lineages and genetic backgrounds. Strong
      synergy is seen in neuronal, renal, breast, lung, and haematopoietic cancer cells
      harboring abnormalities in PTEN, VHL, LKB1, Her2, or KRAS. Critically, in the
      presence of RAD001, the mTOR-4EBP1 pathway and tumorigenesis can be fully
      inhibited using lower doses of BEZ235. This is relevant since RAD001 is
      relatively well tolerated in patients while the toxicity profiles of ATP
      competitive mTOR inhibitors are currently unknown.

PMID- 23155393
TI  - The time course of activation of object shape and shape+colour representations
      during memory retrieval.
AB  - Little is known about the timing of activating memory for objects and their
      associated perceptual properties, such as colour, and yet this is important for
      theories of human cognition. We investigated the time course associated with
      early cognitive processes related to the activation of object shape and object
      shape+colour representations respectively, during memory retrieval as assessed by
      repetition priming in an event-related potential (ERP) study. The main findings
      were as follows: (1) we identified a unique early modulation of mean ERP
      amplitude during the N1 that was associated with the activation of object shape
      independently of colour; (2) we also found a subsequent early P2 modulation of
      mean amplitude over the same electrode clusters associated with the activation of
      object shape+colour representations; (3) these findings were apparent across both
      familiar (i.e., correctly coloured - yellow banana) and novel (i.e., incorrectly
      coloured - blue strawberry) objects; and (4) neither of the modulations of mean
      ERP amplitude were evident during the P3. Together the findings delineate the
      timing of object shape and colour memory systems and support the notion that
      perceptual representations of object shape mediate the retrieval of temporary
      shape+colour representations for familiar and novel objects.

PMID- 23155394
TI  - Honeybees (Apis mellifera) learn color discriminations via differential
      conditioning independent of long wavelength (green) photoreceptor modulation.
AB  - BACKGROUND: Recent studies on colour discrimination suggest that experience is an
      important factor in how a visual system processes spectral signals. In insects it
      has been shown that differential conditioning is important for processing fine
      colour discriminations. However, the visual system of many insects, including the
      honeybee, has a complex set of neural pathways, in which input from the long
      wavelength sensitive ('green') photoreceptor may be processed either as an
      independent achromatic signal or as part of a trichromatic opponent-colour
      system. Thus, a potential confound of colour learning in insects is the
      possibility that modulation of the 'green' photoreceptor could underlie
      observations. METHODOLOGY/PRINCIPAL FINDINGS: We tested honeybee vision using
      light emitting diodes centered on 414 and 424 nm wavelengths, which limit
      activation to the short-wavelength-sensitive ('UV') and medium-wavelength
      sensitive ('blue') photoreceptors. The absolute irradiance spectra of stimuli was
      measured and modelled at both receptor and colour processing levels, and stimuli
      were then presented to the bees in a Y-maze at a large visual angle (26 degrees
      ), to ensure chromatic processing. Sixteen bees were trained over 50 trials,
      using either appetitive differential conditioning (N = 8), or aversive-appetitive
      differential conditioning (N = 8). In both cases the bees slowly learned to
      discriminate between the target and distractor with significantly better accuracy
      than would be expected by chance. Control experiments confirmed that changing
      stimulus intensity in transfers tests does not significantly affect bee
      performance, and it was possible to replicate previous findings that bees do not
      learn similar colour stimuli with absolute conditioning. CONCLUSION: Our data
      indicate that honeybee colour vision can be tuned to relatively small spectral
      differences, independent of 'green' photoreceptor contrast and brightness cues.
      We thus show that colour vision is at least partly experience dependent, and
      behavioural plasticity plays an important role in how bees exploit colour
      information.

PMID- 23155395
TI  - Prediction of the location of the pyramidal tract in patients with thalamic or
      basal ganglia tumors.
AB  - BACKGROUND: Locating the pyramidal tract (PT) is difficult in patients with
      thalamic or basal ganglia tumors, especially when the surrounding anatomical
      structures cannot be identified using computed tomography or magnetic resonance
      images. Hence, we objected to find a way to predict the location of the PT in
      patients with thalamic and basal ganglia tumors METHODOLOGY/PRINCIPAL FINDINGS:
      In 59 patents with thalamic or basal ganglia tumors, the PTs were constructed by
      with diffusion tensor imaging (DTI)-based fiber tracking (FT). In axial slices
      crossing the foramen of Monro, the tumor position was classified according to
      three lines. Line 1 was vertical and crossed the vertex point of the anterior
      limbs of the internal capsule. Lines 2 and line 3 were horizontal and crossed the
      foramen of Monro and joint of the middle and lateral thirds of the posterior
      limbs, respectively. Six (10.17%) patients were diagnosed with type 1 tumor, six
      (10.17%) with type 2, seven (11.86%) with type 3a, five (8.47%) with type 3b, 17
      (28.81%) with type 4a, six (10.17%) with type 4b, three (5.08%) with type 5, and
      nine (15.25%) with type 6. In type 1 tumors, the PTs were located at the 12
      o'clock position of the tumor, type 2 at six o'clock, type 3a between nine and 12
      o'clock, type 3 between six and nine o'clock, type 4a between 12 and three
      o'clock, type 4b at three o'clock, type 5 between six and nine o'clock, and type
      6 between three and six o'clock. CONCLUSIONS/SIGNIFICANCE: The position of the PT
      relative to the tumor could be determined according to the tumor location. These
      results could prove helpful in determining the location of the PT preoperatively.

PMID- 23155397
TI  - Multi-state proteins: approach allowing experimental determination of the
      formation order of structure elements in the green fluorescent protein.
AB  - The most complex problem in studying multi-state protein folding is the
      determination of the sequence of formation of protein intermediate states. A far
      more complex issue is to determine at what stages of protein folding its various
      parts (secondary structure elements) develop. The structure and properties of
      different intermediate states depend in particular on these parts. An
      experimental approach, named MU-analysis, which allows understanding the order of
      formation of structural elements upon folding of a multi-state protein was used
      in this study. In this approach the same elements of the protein secondary
      structure are "tested" by substitutions of single hydrophobic amino acids and by
      incorporation of cysteine bridges. Single substitutions of hydrophobic amino
      acids contribute to yielding information on the late stages of protein folding
      while incorporation of ss-bridges allows obtaining data on the initial stages of
      folding. As a result of such an MU-analysis, we have determined the order of
      formation of beta-hairpins upon folding of the green fluorescent protein.

PMID- 23155396
TI  - Epigenetic and genetic factors predict women's salivary cortisol following a
      threat to the social self.
AB  - Evidence suggests that the reactivity of the Hypothalamus-Pituitary-Adrenal axis
      (HPAA) is modulated by both genetic and environmental variables. Of special
      interest are the underlying molecular mechanisms driving gender differences to
      psychosocial stressors. Epigenetic mechanisms that sculpt the genome are ideal
      candidates for mediating the effects of signals on the HPAA. In the current
      study, we analyzed by pyrosequencing, bisulfite-treated buccal DNA from male and
      female university students who participated in the Trier Social Stress Test
      (TSST). A linear regression model was used to ascertain the effects of sex, CpG
      methylation and genes on stress response. Total cortisol output (area under the
      curve, AUC) was significantly predicted by glucocorticoid receptor (NR3C1) exon
      1F methylation (averaged across 39 CpG sites) solely in female subjects. A single
      CpG site located in the exon 1F noncanonical nerve growth factor-inducible
      protein A (NGFI-A) transcription factor was a highly significant predictor of AUC
      in female subjects. Additionally, variations in the estrogen receptor alpha
      (ESR1) and the serotonin transporter promoter (5-HTTLPR) genes were independent
      additive predictors of AUC. The full model accounted for half of the variance
      (50.06%) in total cortisol output. Notably, this is the first demonstration that
      epigenetic changes at the GR exon 1F correlate with HPAA reactivity. These
      findings have important implications for understanding the molecular mechanisms
      underlying gender differences in stress-related disorders and underscore the
      unique value of modeling both epigenetic and genetic information in conferring
      vulnerability to stress.

PMID- 23155398
TI  - Increased adipogenesis in cultured embryonic chondrocytes and in adult bone
      marrow of dominant negative Erg transgenic mice.
AB  - In monolayer culture, primary articular chondrocytes have an intrinsic tendency
      to lose their phenotype during expansion. The molecular events underlying this
      chondrocyte dedifferentiation are still largely unknown. Several transcription
      factors are important for chondrocyte differentiation. The Ets transcription
      factor family may be involved in skeletal development. One family member, the Erg
      gene, is mainly expressed during cartilage formation. To further investigate the
      potential role of Erg in the maintenance of the chondrocyte phenotype, we
      isolated and cultured chondrocytes from the rib cartilage of embryos of
      transgenic mice that express a dominant negative form of Erg (DN-Erg) during
      cartilage formation. DN-Erg expression in chondrocytes cultured for up to 20 days
      did not affect the early dedifferentiation usually observed in cultured
      chondrocytes. However, lipid droplets accumulated in DN-Erg chondrocytes,
      suggesting adipocyte emergence. Transcriptomic analysis using a DNA microarray,
      validated by quantitative RT-PCR, revealed strong differential gene expression,
      with a decrease in chondrogenesis-related markers and an increase in adipogenesis
      related gene expression in cultured DN-Erg chondrocytes. These results indicate
      that Erg is involved in either maintaining the chondrogenic phenotype in vitro or
      in cell fate orientation. Along with the in vitro studies, we compared adipocyte
      presence in wild-type and transgenic mice skeletons. Histological investigations
      revealed an increase in the number of adipocytes in the bone marrow of adult DN
      Erg mice even though no adipocytes were detected in embryonic cartilage or bone.
      These findings suggest that the Ets transcription factor family may contribute to
      the homeostatic balance in skeleton cell plasticity.

PMID- 23155399
TI  - A nice day for an infection? Weather conditions and social contact patterns
      relevant to influenza transmission.
AB  - Although there is no doubt that significant morbidity and mortality occur during
      annual influenza epidemics, the role of contextual circumstances, which catalyze
      seasonal influenza transmission, remains unclear. Weather conditions are believed
      to affect virus survival, efficiency of transmission and host immunity, but
      seasonality may also be driven by a tendency of people to congregate indoors
      during periods of bad weather. To test this hypothesis, we combined data from a
      social contact survey in Belgium with local weather data. In the absence of a
      previous in-depth weather impact analysis of social contact patterns, we explored
      the possibilities and identified pitfalls. We found general dominance of day-type
      (weekend, holiday, working day) over weather conditions, but nonetheless observed
      an increase in long duration contacts ([Formula: see text]1 hour) on regular
      workdays with low temperatures, almost no precipitation and low absolute humidity
      of the air. Interestingly, these conditions are often assumed to be beneficial
      for virus survival and transmission. Further research is needed to establish the
      impact of the weather on social contacts. We recommend that future studies sample
      over a broad spectrum of weather conditions and day types and include a
      sufficiently large proportion of holiday periods and weekends.

PMID- 23155400
TI  - Rural to urban migration is an unforeseen impact of development intervention in
      Ethiopia.
AB  - Rural development initiatives across the developing world are designed to improve
      community well-being and livelihoods. However they may also have unforeseen
      consequences, in some cases placing further demands on stretched public services.
      In this paper we use data from a longitudinal study of five Ethiopian villages to
      investigate the impact of a recent rural development initiative, installing
      village-level water taps, on rural to urban migration of young adults. Our
      previous research has identified that tap stands dramatically reduced child
      mortality, but were also associated with increased fertility. We demonstrate that
      the installation of taps is associated with increased rural-urban migration of
      young adults (15-30 years) over a 15 year period (15.5% migrate out, n = 1912
      from 1280 rural households). Young adults with access to this rural development
      intervention had three times the relative risk of migrating to urban centres
      compared to those without the development. We also identify that family dynamics,
      specifically sibling competition for limited household resources (e.g. food,
      heritable land and marriage opportunities), are key to understanding the timing
      of out-migration. Birth of a younger sibling doubled the odds of out-migration
      and starting married life reduced it. Rural out-migration appears to be a
      response to increasing rural resource scarcity, principally competition for
      agricultural land. Strategies for livelihood diversification include education
      and off-farm casual wage-labour. However, jobs and services are limited in urban
      centres, few migrants send large cash remittances back to their families, and
      most return to their villages within one year without advanced qualifications.
      One benefit for returning migrants may be through enhanced social prestige and
      mate-acquisition on return to rural areas. These findings have wide implications
      for current understanding of the processes which initiate rural-to-urban
      migration and transitions to low fertility, as well as for the design and
      implementation of development intervention across the rural and urban developing
      world.

PMID- 23155401
TI  - Photoinduced disaggregation of TiO2 nanoparticles enables transdermal
      penetration.
AB  - Under many aqueous conditions, metal oxide nanoparticles attract other
      nanoparticles and grow into fractal aggregates as the result of a balance between
      electrostatic and Van Der Waals interactions. Although particle coagulation has
      been studied for over a century, the effect of light on the state of aggregation
      is not well understood. Since nanoparticle mobility and toxicity have been shown
      to be a function of aggregate size, and generally increase as size decreases,
      photo-induced disaggregation may have significant effects. We show that ambient
      light and other light sources can partially disaggregate nanoparticles from the
      aggregates and increase the dermal transport of nanoparticles, such that small
      nanoparticle clusters can readily diffuse into and through the dermal profile,
      likely via the interstitial spaces. The discovery of photoinduced disaggregation
      presents a new phenomenon that has not been previously reported or considered in
      coagulation theory or transdermal toxicological paradigms. Our results show that
      after just a few minutes of light, the hydrodynamic diameter of TiO(2) aggregates
      is reduced from ~280 nm to ~230 nm. We exposed pigskin to the nanoparticle
      suspension and found 200 mg kg(-1) of TiO(2) for skin that was exposed to
      nanoparticles in the presence of natural sunlight and only 75 mg kg(-1) for skin
      exposed to dark conditions, indicating the influence of light on NP penetration.
      These results suggest that photoinduced disaggregation may have important health
      implications.

PMID- 23155402
TI  - Pathways to age of onset of heroin use: a structural model approach exploring the
      relationship of the COMT gene, impulsivity and childhood trauma.
AB  - BACKGROUND: The interaction of the association of dopamine genes, impulsivity and
      childhood trauma with substance abuse remains unclear. OBJECTIVES: To clarify the
      impacts and the interactions of the Catechol -O-methyltransferase (COMT) gene,
      impulsivity and childhood trauma on the age of onset of heroin use among heroin
      dependent patients in China. METHODS: 202 male and 248 female inpatients who meet
      DSM-IV criteria of heroin dependence were enrolled. Impulsivity and childhood
      trauma were measured using BIS-11 (Barratt Impulsiveness Scale-11) and ETISR-SF
      (Early Trauma Inventory Self Report-Short Form). The single nucleotide
      polymorphism (SNP) rs737866 on the COMT gene-which has previously been associated
      with heroin abuse, was genotyped using a DNA sequence detection system.
      Structural equations model was used to assess the interaction paths between these
      factors and the age of onset of heroin use. PRINCIPAL FINDINGS: Chi-square test
      indicated the individuals with TT allele have earlier age of onset of heroin use
      than those with CT or CC allele. In the correlation analysis, the severity of
      childhood trauma was positively correlated to impulsive score, but both of them
      were negatively related to the age of onset of heroin use. In structure equation
      model, both the COMT gene and childhood trauma had impacts on the age of onset of
      heroin use directly or via impulsive personality. CONCLUSIONS: Our findings
      indicated that the COMT gene, impulsive personality traits and childhood trauma
      experience were interacted to impact the age of onset of heroin use, which play a
      critical role in the development of heroin dependence. The impact of
      environmental factor was greater than the COMT gene in the development of heroin
      dependence.

PMID- 23155403
TI  - Identification of a plant viral RNA genome in the nucleus.
AB  - Viruses contain either DNA or RNA as genomes. DNA viruses replicate within
      nucleus, while most RNA viruses, especially (+)-sense single-stranded RNA,
      replicate and are present within cytoplasm. We proposed a new thought that is
      contrary to the common notion that (+)-sense single-stranded RNA viruses are
      present only in the cytoplasm. In this study, we question whether the genome of a
      plant RNA virus (non-retroviral) is present in the nucleus of infected cells?
      Hibiscus chlorotic ringspot virus (HCRSV) RNA was detected in the nucleus of
      infected cells, as shown by fluorescent in situ hybridization. Western blot using
      anti-histone 3 and anti-phosphoenolpyruvate carboxylase showed that nuclei were
      highly purified from mock and HCRSV-infected kenaf (Hibiscus cannabilis L.)
      leaves, respectively. The p23 and HCRSV coat protein (CP) coding regions were
      both amplified from total RNA extracted from isolated nuclei. Viral RNA in the
      nucleus may be used to generate viral microRNAs (vir-miRNAs), as five putative
      vir-miRNAs were predicted from HCRSV using the vir-miRNAs prediction database.
      The vir-miRNA (hcrsv-miR-H1-5p) was detected using TaqMan(r) stem-loop real-time
      PCR, and by northern blot using DIG-end labeled probe in HCRSV-infected kenaf
      leaves. Finally, a novel nuclear localization signal (NLS) was discovered in p23
      of HCRSV. The NLS interacts with importin alpha and facilitates viral RNA genome
      to enter nucleus. We demonstrate the presence of a (+)-sense single-stranded
      viral RNA within nucleus.

PMID- 23155404
TI  - Mos1-mediated transgenesis to probe consequences of single gene mutations in
      variation-rich isolates of Caenorhabditis elegans.
AB  - Caenorhabditis elegans, especially the N2 isolate, is an invaluable biological
      model system. Numerous additional natural C. elegans isolates have been shown to
      have unexpected genotypic and phenotypic variations which has encouraged
      researchers to use next generation sequencing methodology to develop a more
      complete picture of genotypic variations among the isolates. To understand the
      phenotypic effects of a genomic variation (GV) on a single gene, in a variation
      rich genetic background, one should analyze that particular GV in a well
      understood genetic background. In C. elegans, the analysis is usually done in N2,
      which requires extensive crossing to bring in the GV. This can be a very time
      consuming procedure thus it is important to establish a fast and efficient
      approach to test the effect of GVs from different isolates in N2. Here we use a
      Mos1-mediated single-copy insertion (MosSCI) method for phenotypic assessments of
      GVs from the variation-rich Hawaiian strain CB4856 in N2. Specifically, we
      investigate effects of variations identified in the CB4856 strain on tac-1 which
      is an essential gene that is necessary for mitotic spindle elongation and
      pronuclear migration. We show the usefulness of the MosSCI method by using EU1004
      tac-1(or402) as a control. or402 is a temperature sensitive lethal allele within
      a well-conserved TACC domain (transforming acidic coiled-coil) that results in a
      leucine to phenylalanine change at amino acid 229. CB4856 contains a variation
      that affects the second exon of tac-1 causing a cysteine to tryptophan change at
      amino acid 94 also within the TACC domain. Using the MosSCI method, we analyze
      tac-1 from CB4856 in the N2 background and demonstrate that the C94W change,
      albeit significant, does not cause any obvious decrease in viability. This MosSCI
      method has proven to be a rapid and efficient way to analyze GVs.

PMID- 23155405
TI  - Biomarkers of Plasmodium falciparum infection during pregnancy in women living in
      northeastern Tanzania.
AB  - In pregnant women, Plasmodium falciparum infections are an important cause of
      maternal morbidity as well as fetal and neonatal mortality. Erythrocytes infected
      by these malaria-causing parasites accumulate through adhesive interactions in
      placental intervillous spaces, thus evading detection in peripheral blood smears.
      Sequestered infected erythrocytes induce inflammation, offering the possibility
      of detecting inflammatory mediators in peripheral blood that could act as
      biomarkers of placental infection. In a longitudinal, prospective study in
      Tanzania, we quantified a range of different cytokines, chemokines and angiogenic
      factors in peripheral plasma samples, taken on multiple sequential occasions
      during pregnancy up to and including delivery, from P. falciparum-infected women
      and matched uninfected controls. The results show that during healthy, uninfected
      pregnancies the levels of most of the panel of molecules we measured were largely
      unchanged except at delivery. In women with P. falciparum, however, both
      comparative and longitudinal assessments consistently showed that the levels of
      IL-10 and IP-10 increased significantly whilst that of RANTES decreased
      significantly, regardless of gestational age at the time the infection was
      detected. ROC curve analysis indicated that a combination of increased IL-10 and
      IP-10 levels and decreased RANTES levels might be predictive of P. falciparum
      infections. In conclusion, our data suggest that host biomarkers in peripheral
      blood may represent useful diagnostic markers of P. falciparum infection during
      pregnancy, but placental histology results would need to be included to verify
      these findings.

PMID- 23155406
TI  - Plac8 is required for white adipocyte differentiation in vitro and cell number
      control in vivo.
AB  - Plac8 belongs to an evolutionary conserved family of proteins, mostly abundant in
      plants where they control fruit weight through regulation of cell number. In
      mice, Plac8 is expressed both in white and brown adipose tissues and we
      previously showed that Plac8(-/-) mice develop late-onset obesity, with abnormal
      brown fat differentiation and reduced thermogenic capacity. We also showed that
      in brown adipocytes, Plac8 is an upstream regulator of C/EBPbeta expression.
      Here, we first assessed the role of Plac8 in white adipogenesis in vitro. We show
      that Plac8 is induced early after induction of 3T3-L1 adipocytes differentiation,
      a process that is prevented by Plac8 knockdown; similarly, embryonic fibroblasts
      obtained from Plac8 knockout mice failed to form adipocytes upon stimulation of
      differentiation. Knockdown of Plac8 in 3T3-L1 was associated with reduced
      expression of C/EBPbeta, Krox20, and Klf4, early regulators of the white
      adipogenic program, and we show that Plac8 could transactivate the C/EBPbeta
      promoter. In vivo, we show that absence of Plac8 led to increased white fat mass
      with enlarged adipocytes but reduced total number of adipocytes. Finally, even
      though Plac8(-/-) mice showed impaired thermogenesis due to brown fat
      dysfunction, this was not associated with changes in glycemia or plasma free
      fatty acid and triglyceride levels. Collectively, these data indicate that Plac8
      is an upstream regulator of C/EBPbeta required for adipogenesis in vitro.
      However, in vivo, Plac8 is dispensable for the differentiation of white
      adipocytes with preserved fat storage capacity but is required for normal fat
      cell number regulation.

PMID- 23155407
TI  - Chronic temporal lobe epilepsy is associated with enhanced Alzheimer-like
      neuropathology in 3*Tg-AD mice.
AB  - The comorbidity between epilepsy and Alzheimer's disease (AD) is a topic of
      growing interest. Senile plaques and tauopathy are found in epileptic human
      temporal lobe structures, and individuals with AD have an increased incidence of
      spontaneous seizures. However, why and how epilepsy is associated with enhanced
      AD-like pathology remains unknown. We have recently shown beta-secretase-1
      (BACE1) elevation associated with aberrant limbic axonal sprouting in epileptic
      CD1 mice. Here we sought to explore whether BACE1 upregulation affected the
      development of Alzheimer-type neuropathology in mice expressing mutant human APP,
      presenilin and tau proteins, the triple transgenic model of AD (3*Tg-AD). 3*Tg-AD
      mice were treated with pilocarpine or saline (i.p.) at 6-8 months of age.
      Immunoreactivity (IR) for BACE1, beta-amyloid (Abeta) and phosphorylated tau (p
      tau) was subsequently examined at 9, 11 or 14 months of age. Recurrent convulsive
      seizures, as well as mossy fiber sprouting and neuronal death in the hippocampus
      and limbic cortex, were observed in all epileptic mice. Neuritic plaques composed
      of BACE1-labeled swollen/sprouting axons and extracellular AbetaIR were seen in
      the hippocampal formation, amygdala and piriform cortices of 9 month-old
      epileptic, but not control, 3*Tg-AD mice. Densities of plaque-associated BACE1
      and AbetaIR were elevated in epileptic versus control mice at 11 and 14 months of
      age. p-Tau IR was increased in dentate granule cells and mossy fibers in
      epileptic mice relative to controls at all time points examined. Thus,
      pilocarpine-induced chronic epilepsy was associated with accelerated and enhanced
      neuritic plaque formation and altered intraneuronal p-tau expression in temporal
      lobe structures in 3*Tg-AD mice, with these pathologies occurring in regions
      showing neuronal death and axonal dystrophy.

PMID- 23155408
TI  - The temporal dynamics of early visual cortex involvement in behavioral priming.
AB  - Transcranial magnetic stimulation (TMS) allows for non-invasive interference with
      ongoing neural processing. Applied in a chronometric design over early visual
      cortex (EVC), TMS has proved valuable in indicating at which particular time
      point EVC must remain unperturbed for (conscious) vision to be established. In
      the current study, we set out to examine the effect of EVC TMS across a broad
      range of time points, both before (pre-stimulus) and after (post-stimulus) the
      onset of symbolic visual stimuli. Behavioral priming studies have shown that the
      behavioral impact of a visual stimulus can be independent from its conscious
      perception, suggesting two independent neural signatures. To assess whether TMS
      induced suppression of visual awareness can be dissociated from behavioral
      priming in the temporal domain, we thus implemented three different measures of
      visual processing, namely performance on a standard visual discrimination task, a
      subjective rating of stimulus visibility, and a visual priming task. To control
      for non-neural TMS effects, we performed electrooculographical recordings,
      placebo TMS (sham), and control site TMS (vertex). Our results suggest that, when
      considering the appropriate control data, the temporal pattern of EVC TMS
      disruption on visual discrimination, subjective awareness and behavioral priming
      are not dissociable. Instead, TMS to EVC disrupts visual perception holistically,
      both when applied before and after the onset of a visual stimulus. The current
      findings are discussed in light of their implications on models of visual
      awareness and (subliminal) priming.

PMID- 23155409
TI  - Food webs in the human body: linking ecological theory to viral dynamics.
AB  - The dynamics of in-host infections are central to predicting the progression of
      natural infections and the effectiveness of drugs or vaccines, however, they are
      not well understood. Here, we apply food web theory to in-host disease networks
      of the human body that are structured similarly to food web models that treat
      both predation and competition simultaneously. We show that in-host trade-offs,
      an under-studied aspect of disease ecology, are fundamental to understanding the
      outcomes of competing viral strains under differential immune responses. Further,
      and importantly, our analysis shows that the outcome of competition between
      virulent and non-virulent strains can be highly contingent on the abiotic
      conditions prevailing in the human body. These results suggest the alarming idea
      that even subtle behavioral changes that alter the human body (e.g. weight gain,
      smoking) may switch the environmental conditions in a manner that suddenly allows
      a virulent strain to dominate and replace less virulent strains. These ecological
      results therefore cast new light on the control of disease in the human body, and
      highlight the importance of longitudinal empirical studies across host variation
      gradients, as well as, of studies focused on delineating life history trade-offs
      within hosts.

PMID- 23155410
TI  - AtaA, a new member of the trimeric autotransporter adhesins from Acinetobacter
      sp. Tol 5 mediating high adhesiveness to various abiotic surfaces.
AB  - Acinetobacter sp. Tol 5 exhibits an autoagglutinating nature and noteworthy
      adhesiveness to various abiotic surfaces from hydrophobic plastics to hydrophilic
      glass and stainless steel. Although previous studies have suggested that
      bacterionanofibers on Tol 5 cells are involved in the adhesive phenotype of Tol
      5, the fiber that directly mediates Tol 5 adhesion has remained unknown. Here, we
      present a new member of trimeric autotransporter adhesins designated AtaA, which
      we discovered by analyzing a less adhesive mutant of Tol 5, T1, obtained by
      transposon mutagenesis. AtaA forms thinner and shorter nanofibers than fimbriae
      on Tol 5 cells. We performed target disruption of ataA by allelic marker
      exchange, and the resulting DeltaataA strain was complemented with ataA on the
      Escherichia coli-Acinetobacter shuttle vector, which was newly constructed. These
      results proved that AtaA is essential for Tol 5's autoagglutinating nature and
      high adhesiveness to surfaces of various materials. In addition, the adhesiveness
      to solid surfaces mediated by AtaA is notably higher than that mediated by YadA
      of Yersinia enterocolitica WA-314. Moreover, and importantly, these
      characteristics can be conferred to the non-adhesive, non-agglutinating bacterium
      Acinetobacter sp. ADP1 in trans by transformation with ataA, with expected
      applications to microbial immobilization.

PMID- 23155411
TI  - HERVs expression in Autism Spectrum Disorders.
AB  - BACKGROUND: Autistic Spectrum Disorder (ASD) is a heterogeneous
      neurodevelopmental disorder, resulting from complex interactions among genetic,
      genomic and environmental factors. Here we have studied the expression of Human
      Endogenous Retroviruses (HERVs), non-coding DNA elements with potential
      regulatory functions, and have tested their possible implication in autism.
      METHODS: The presence of retroviral mRNAs from four HERV families (E, H, K and
      W), widely implicated in complex diseases, was evaluated in peripheral blood
      mononuclear cells (PBMCs) from ASD patients and healthy controls (HCs) by
      qualitative RT-PCR. We also analyzed the expression of the env sequence from HERV
      H, HERV-W and HERV-K families in PBMCs at the time of sampling and after
      stimulation in culture, in both ASD and HC groups, by quantitative Real-time PCR.
      Differences between groups were evaluated using statistical methods. RESULTS: The
      percentage of HERV-H and HERV-W positive samples was higher among ASD patients
      compared to HCs, while HERV-K was similarly represented and HERV-E virtually
      absent in both groups. The quantitative evaluation shows that HERV-H and HERV-W
      are differentially expressed in the two groups, with HERV-H being more abundantly
      expressed and, conversely, HERV-W, having lower abundance, in PBMCs from ASDs
      compared to healthy controls. PMBCs from ASDs also showed an increased potential
      to up-regulate HERV-H expression upon stimulation in culture, unlike HCs.
      Furthermore we report a negative correlation between expression levels of HERV-H
      and age among ASD patients and a statistically significant higher expression in
      ASD patients with Severe score in Communication and Motor Psychoeducational
      Profile-3. CONCLUSIONS: Specific HERV families have a distinctive expression
      profile in ASD patients compared to HCs. We propose that HERV-H expression be
      explored in larger samples of individuals with autism spectrum in order to
      determine its utility as a novel biological trait of this complex disorder.

PMID- 23155412
TI  - Utility of the trnH-psbA intergenic spacer region and its combinations as plant
      DNA barcodes: a meta-analysis.
AB  - BACKGROUND: The trnH-psbA intergenic spacer region has been used in many DNA
      barcoding studies. However, a comprehensive evaluation with rigorous sequence
      preprocessing and statistical testing on the utility of trnH-psbA and its
      combinations as DNA barcodes is lacking. METHODOLOGY/PRINCIPAL FINDINGS:
      Sequences were searched from GenBank for a meta-analysis on the usefulness of
      trnH-psbA and its combinations as DNA barcodes. After preprocessing, we
      constructed full and matching data sets that contained 17 983 trnH-psbA sequences
      and 2190 sets of trnH-psbA, matK, rbcL, and ITS2 sequences from the same sample,
      repectively. These datasets were used to analyze the ability of trnH-psbA and its
      combinations to discriminate species by the BLAST and BLAST+P methods. The
      Fisher's exact test was used to evaluate the significance of performance
      differences. For the full data set, the identification success rates of trnH-psbA
      exceeded 70% in 18 families and 12 genera, respectively. For the matching data
      set, the identification rates of trnH-psbA were significantly higher than those
      of the other loci in two families and four genera. Similarly, the identification
      rates of trnH-psbA+ITS2 were significantly higher than those of matK+rbcL in 18
      families and 21 genera. CONCLUSION/SIGNIFICANE: This study provides valuable
      information on the higher utility of trnH-psbA and its combinations. We found
      that trnH-psbA+ITS2 combination performs better or equally well compared with
      other combinations in most taxonomic groups investigated. This information will
      guide the optimal usage of trnH-psbA and its combinations for species
      identification.

PMID- 23155413
TI  - Socio-economic and health access determinants of breast and cervical cancer
      screening in low-income countries: analysis of the World Health Survey.
AB  - BACKGROUND: Breast and Cervical cancer are the two most common cancers among
      women in developing countries. Regular screening is the most effective way of
      ensuring that these cancers are detected at early stages; however few studies
      have assessed factors that predict cancer screening in developing countries.
      PURPOSE: To assess the influence of household socio-economic status (SES),
      healthcare access and country level characteristics on breast and cervical cancer
      screening among women in developing countries. METHODS: Women ages 18-69 years
      (cervical cancer screening) and 40-69 years (breast cancer screening) from 15
      developing countries who participated in the 2003 World Health Survey provided
      data for this study. Household SES and healthcare access was assessed based on
      self-reported survey responses. SAS survey procedures (SAS, Version 9.2) were
      used to assess determinants of breast and cervical cancer screening in separate
      models. RESULTS: 4.1% of women ages 18-69 years had received cervical cancer
      screening in the past three years, while only 2.2% of women ages 40-69 years had
      received breast cancer screening in the past 5 years in developing countries.
      Cancer screening rates varied by country; cervical cancer screening ranged from
      1.1% in Bangladesh to 57.6% in Congo and breast cancer screening ranged from 0%
      in Mali to 26% in Congo. Significant determinants of cancer screening were
      household SES, rural residence, country health expenditure (as a percent of GDP)
      as well as healthcare access. DISCUSSION: A lot more needs to be done to improve
      screening rates for breast and cervical cancer in developing countries, such as
      increasing health expenditure (especially in rural areas), applying the increased
      funds towards the provision of more, better educated health providers as well as
      improved infrastructure.

PMID- 23155415
TI  - Dysregulation of IRP1-mediated iron metabolism causes gamma ray-specific
      radioresistance in leukemia cells.
AB  - Iron is required for nearly all organisms, playing important roles in oxygen
      transport and many enzymatic reactions. Excess iron, however, can be cytotoxic.
      Emerging evidence suggests that radioresistance can be achieved in lower
      organisms by the protection of proteins, but not DNA, immediately following
      ionizing radiation (IR) exposure, allowing for improved DNA repair. One potential
      mechanism for protein protection is controlling and limiting the amount of free
      iron in cells, as has been demonstrated in the extremophile Deinococcus
      Radiodurans, reducing the potential for oxidative damage to proteins during
      exposure to IR. We found that iron regulatory protein 1 (IRP1) expression was
      markedly reduced in human myeloid leukemia HL60 cells resistant to low linear
      energy transfer (LET) gamma rays, but not to high LET alpha particles. Stable
      knockdown of IRP1 by short-hairpin RNA (shRNA) interference in radiosensitive
      parental cells led to radioresistance to low LET IR, reduced intracellular Fenton
      chemistry, reduced protein oxidation, and more rapid DNA double-strand break
      (DSB) repair. The mechanism of radioresistance appeared to be related to
      attenuated free radical-mediated cell death. Control of intracellular iron by
      IRPs may be a novel radioresistance mechanism in mammalian cells.

PMID- 23155416
TI  - Liking food less: the impact of social influence on food liking evaluations in
      female students.
AB  - Social factors are known to influence food intake and choice. However, whether
      social influence acts on evaluations of food and drink liking has not been
      studied. Across two studies, we tested whether leading a participant to believe
      that other people do not like a food affects food liking evaluations. In Study 1,
      we exposed participants to social normative information suggesting a) that an in
      group disliked orange juice, b) that an out-group disliked orange juice or c)
      that an in-group were neutral about orange juice. We then examined how much
      participants believed they liked orange juice. In Study 2, participants consumed
      a snack food before being led to believe that two previous participants had also
      eaten the food and either disliked or quite liked it. We asked participants to
      rate how much they had enjoyed eating the snack food. Across both studies, social
      influence was observed, as underlined by decreases in liking evaluations. In
      Study 1, beliefs about liking were only influenced by social normative
      information when the norm was expressed by an in-group. In Study 2, exposure to
      others' accounts of a negative experience with a food decreased evaluated liking
      of the recent consumption experience. These results suggest that social influence
      can act upon food liking evaluations.

PMID- 23155414
TI  - Association of genetic loci with sleep apnea in European Americans and African
      Americans: the Candidate Gene Association Resource (CARe).
AB  - Although obstructive sleep apnea (OSA) is known to have a strong familial basis,
      no genetic polymorphisms influencing apnea risk have been identified in cross
      cohort analyses. We utilized the National Heart, Lung, and Blood Institute
      (NHLBI) Candidate Gene Association Resource (CARe) to identify sleep apnea
      susceptibility loci. Using a panel of 46,449 polymorphisms from roughly 2,100
      candidate genes on a customized Illumina iSelect chip, we tested for association
      with the apnea hypopnea index (AHI) as well as moderate to severe OSA (AHI>=15)
      in 3,551 participants of the Cleveland Family Study and two cohorts participating
      in the Sleep Heart Health Study.Among 647 African-Americans, rs11126184 in the
      pleckstrin (PLEK) gene was associated with OSA while rs7030789 in the
      lysophosphatidic acid receptor 1 (LPAR1) gene was associated with AHI using a
      chip-wide significance threshold of p-value<2*10(-6). Among 2,904 individuals of
      European ancestry, rs1409986 in the prostaglandin E2 receptor (PTGER3) gene was
      significantly associated with OSA. Consistency of effects between rs7030789 and
      rs1409986 in LPAR1 and PTGER3 and apnea phenotypes were observed in independent
      clinic-based cohorts.Novel genetic loci for apnea phenotypes were identified
      through the use of customized gene chips and meta-analyses of cohort data with
      replication in clinic-based samples. The identified SNPs all lie in genes
      associated with inflammation suggesting inflammation may play a role in OSA
      pathogenesis.

PMID- 23155417
TI  - Evaluation of forest recovery over time and space using permanent plots monitored
      over 30 years in a Jamaican montane rain forest.
AB  - Conservation of tropical forest biodiversity increasingly depends on its recovery
      following severe human disturbance. Our ability to measure recovery using current
      similarity indices suffers from two limitations: different sized individuals are
      treated as equal, and the indices are proportionate (a community with twice the
      individuals of every species as compared with the reference community would be
      assessed as identical). We define an alternative recovery index for trees - the
      Tanner index, as the mean of the quantitative Bray-Curtis similarity indices of
      species composition for stem density and for basal area. We used the new index to
      compare the original (pre-gap) and post-gap composition of five experimental gap
      plots (each 90-100 m(2)) and four control plots over 24-35 years in the Blue
      Mountains of Jamaica. After 24-35 years, these small gaps surrounded by
      undisturbed forest had recovered 68% of the sum of per species stem density and
      29% of the sum of per species basal area, a recovery index of 47%. Four endemic
      species were especially reduced in density and basal area. With the incorporation
      of basal area and stem density, our index reduces over-estimations of forest
      recovery obtained using existing similarity indices (by 24%-41%), and thus yields
      more accurate estimates of forest conservation status. Finally, our study
      indicates that the two kinds of comparisons: 1) over time between pre-gap and
      post-gap composition and 2) over space between gap plots and spatial controls
      (space-for-time substitution) yield broadly similar results, which supports the
      value of using space-for-time substitutions in studying forest recovery, at least
      in this tropical montane forest.

PMID- 23155419
TI  - Exome analysis of two limb-girdle muscular dystrophy families: mutations
      identified and challenges encountered.
AB  - The molecular diagnosis of muscle disorders is challenging: genetic heterogeneity
      (>100 causal genes for skeletal and cardiac muscle disease) precludes exhaustive
      clinical testing, prioritizing sequencing of specific genes is difficult due to
      the similarity of clinical presentation, and the number of variants returned
      through exome sequencing can make the identification of the disease-causing
      variant difficult. We have filtered variants found through exome sequencing by
      prioritizing variants in genes known to be involved in muscle disease while
      examining the quality and depth of coverage of those genes. We ascertained two
      families with autosomal dominant limb-girdle muscular dystrophy of unknown
      etiology. To identify the causal mutations in these families, we performed exome
      sequencing on five affected individuals using the Agilent SureSelect Human All
      Exon 50 Mb kit and the Illumina HiSeq 2000 (2*100 bp). We identified causative
      mutations in desmin (IVS3+3A>G) and filamin C (p.W2710X), and augmented the
      phenotype data for individuals with muscular dystrophy due to these mutations. We
      also discuss challenges encountered due to depth of coverage variability at
      specific sites and the annotation of a functionally proven splice site variant as
      an intronic variant.

PMID- 23155418
TI  - Cell-type specific expression of the vasopressin gene analyzed by AAV mediated
      gene delivery of promoter deletion constructs into the rat SON in vivo.
AB  - The magnocellular neurons (MCNs) in the supraoptic nucleus (SON) of the
      hypothalamus selectively express either oxytocin (Oxt) or vasopressin (Avp)
      neuropeptide genes. In this paper we examine the cis-regulatory domains in the
      Avp gene promoter that are responsible for its cell-type specific expression. AAV
      vectors that contain various Avp gene promoter deletion constructs using EGFP as
      the reporter were stereotaxically injected into the rat SON. Two weeks following
      the injection immunohistochemical assays of EGFP expression from these constructs
      were done to determine whether the expressed EGFP reporter co-localizes with
      either the Oxt- or Avp-immunoreactivity in the MCNs. The results identify three
      major enhancer domains located at -2.0 to -1.5 kbp, -1.5 to -950 bp, and -950 to 
      543 bp in the Avp gene promoter that regulate the expression in Avp MCNs. The
      results also show that cell-type specific expression in Avp MCNs is maintained in
      constructs containing at least 288 bp of the promoter region upstream of the
      transcription start site, but this specificity is lost at 116 bp and below. Based
      on these data, we hypothesize that the -288 bp to -116 bp domain contains an Avp
      MCN specific activator and a possible repressor that inhibits expression in Oxt
      MCNs, thereby leading to the cell-type specific expression of the Avp gene only
      in the Avp-MCNs.

PMID- 23155420
TI  - Cross regulation of sirtuin 1, AMPK, and PPARgamma in conjugated linoleic acid
      treated adipocytes.
AB  - Trans-10, cis-12 conjugated linoleic acid (t10c12 CLA) reduces triglyceride (TG)
      levels in adipocytes through multiple pathways, with AMP-activated protein kinase
      (AMPK) generally facilitating, and peroxisome proliferator-activated receptor
      gamma (PPARgamma) generally opposing these reductions. Sirtuin 1 (SIRT1), a
      histone/protein deacetylase that affects energy homeostasis, often functions
      coordinately with AMPK, and is capable of binding to PPARgamma, thereby
      inhibiting its activity. This study investigated the role of SIRT1 in the
      response of 3T3-L1 adipocytes to t10c12 CLA by testing the following hypotheses:
      1) SIRT1 is functionally required for robust TG reduction; and 2) SIRT1, AMPK,
      and PPARgamma cross regulate each other. These experiments were performed by
      using activators, inhibitors, or siRNA knockdowns that affected these pathways in
      t10c12 CLA-treated 3T3-L1 adipocytes. Inhibition of SIRT1 amounts or activity
      using siRNA, sirtinol, nicotinamide, or etomoxir attenuated the amount of TG
      loss, while SIRT1 activator SRT1720 increased the TG loss. SRT1720 increased AMPK
      activity while sirtuin-specific inhibitors decreased AMPK activity. Reciprocally,
      an AMPK inhibitor reduced SIRT1 activity. Treatment with t10c12 CLA increased
      PPARgamma phosphorylation in an AMPK-dependent manner and increased the amount of
      PPARgamma bound to SIRT1. Reciprocally, a PPARgamma agonist attenuated AMPK and
      SIRT1 activity levels. These results indicated SIRT1 increased TG loss and that
      cross regulation between SIRT1, AMPK, and PPARgamma occurred in 3T3-L1 adipocytes
      treated with t10c12 CLA.

PMID- 23155421
TI  - Isolated Toll-like receptor transmembrane domains are capable of oligomerization.
AB  - Toll-like receptors (TLRs) act as the first line of defense against bacterial and
      viral pathogens by initiating critical defense signals upon dimer activation. The
      contribution of the transmembrane domain in the dimerization and signaling
      process has heretofore been overlooked in favor of the extracellular and
      intracellular domains. As mounting evidence suggests that the transmembrane
      domain is a critical region in several protein families, we hypothesized that
      this was also the case for Toll-like receptors. Using a combined biochemical and
      biophysical approach, we investigated the ability of isolated Toll-like receptor
      transmembrane domains to interact independently of extracellular domain
      dimerization. Our results showed that the transmembrane domains had a preference
      for the native dimer partners in bacterial membranes for the entire receptor
      family. All TLR transmembrane domains showed strong homotypic interaction
      potential. The TLR2 transmembrane domain demonstrated strong heterotypic
      interactions in bacterial membranes with its known interaction partners, TLR1 and
      TLR6, as well as with a proposed interaction partner, TLR10, but not with TLR4,
      TLR5, or unrelated transmembrane receptors providing evidence for the specificity
      of TLR2 transmembrane domain interactions. Peptides for the transmembrane domains
      of TLR1, TLR2, and TLR6 were synthesized to further study this subfamily of
      receptors. These peptides validated the heterotypic interactions seen in
      bacterial membranes and demonstrated that the TLR2 transmembrane domain had
      moderately strong interactions with both TLR1 and TLR6. Combined, these results
      suggest a role for the transmembrane domain in Toll-like receptor oligomerization
      and as such, may be a novel target for further investigation of new therapeutic
      treatments of Toll-like receptor mediated diseases.

PMID- 23155422
TI  - Prospective analysis of the association of a common variant of FTO (rs9939609)
      with adiposity in children: results of the IDEFICS study.
AB  - OBJECTIVES: We investigated cross-sectionally and longitudinally the relationship
      between FTO rs9939609 and obesity-related characteristics in the European
      children of the IDEFICS project and the interaction of this variant with a
      lifestyle intervention. POPULATION AND METHODS: A cohort of 16224 children (2-9
      years) was recruited into a population-based survey (T0) from eight European
      countries. A second survey (T1) reassessed the children two years later. A random
      sample of 4405 children was extracted for genetic studies. 3168 children were re
      examined two years later. Half of them underwent a lifestyle intervention
      program. The FTO rs9939609 was genotyped. Weight, height, waist circumference,
      triceps and subscapular skinfolds were measured at T0 and T1. RESULTS: At T0, the
      risk A allele of rs9939609 was significantly associated with higher values of
      body mass index (BMI), waist circumference and skinfolds (age, sex, and country
      adjusted p-values: all p<0.001) and with a statistically significant increased
      risk of overweight/obesity. Over the two year follow-up, no interaction between
      genotype and intervention was observed. The A allele was associated to a
      significantly higher increase in all the anthropometric variables examined at T0
      independently from the study group (intervention versus control) (p-values: all
      p<0.002, adjusted for age, sex, country, intervention/control study group, T0
      values, and individual time interval between T0 and T1). Over the two-year follow
      up, 210 new cases of overweight/obesity occurred. A statistically significant
      higher incidence of overweight/obesity was associated to the A allele [OR(A) =
      1.95, 95% CI = (1.29; 2.97)]. CONCLUSIONS: We confirmed the association between
      the FTO rs9939609 and body mass and overweight/obesity risk in European children.
      The main finding of the study is that the A allele carriers present higher
      increase of body mass and central adiposity over time and higher risk of
      developing overweight/obesity during growth, independently from intervention
      measures.

PMID- 23155423
TI  - Impaired skeletal muscle regeneration in the absence of fibrosis during
      hibernation in 13-lined ground squirrels.
AB  - Skeletal muscle atrophy can occur as a consequence of immobilization and/or
      starvation in the majority of vertebrates studied. In contrast, hibernating
      mammals are protected against the loss of muscle mass despite long periods of
      inactivity and lack of food intake. Resident muscle-specific stem cells
      (satellite cells) are known to be activated by muscle injury and their activation
      contributes to the regeneration of muscle, but whether satellite cells play a
      role in hibernation is unknown. In the hibernating 13-lined ground squirrel we
      show that muscles ablated of satellite cells were still protected against
      atrophy, demonstrating that satellite cells are not involved in the maintenance
      of skeletal muscle during hibernation. Additionally, hibernating skeletal muscle
      showed extremely slow regeneration in response to injury, due to repression of
      satellite cell activation and myoblast differentiation caused by a fine-tuned
      interplay of p21, myostatin, MAPK, and Wnt signaling pathways. Interestingly,
      despite long periods of inflammation and lack of efficient regeneration, injured
      skeletal muscle from hibernating animals did not develop fibrosis and was capable
      of complete recovery when animals emerged naturally from hibernation. We propose
      that hibernating squirrels represent a new model system that permits evaluation
      of impaired skeletal muscle remodeling in the absence of formation of tissue
      fibrosis.

PMID- 23155424
TI  - Adiponectin mediated MHC class II mismatched cardiac graft rejection in mice is
      IL-4 dependent.
AB  - BACKGROUND: Adiponectin regulates glucose and fatty-acid metabolism but its role
      in chronic graft rejection mediated by Th2 cytokines remains ill-defined.
      METHODOLOGY/PRINCIPAL FINDINGS: Wild type and adiponectin-null mice were used as
      graft recipients in mouse MHC class II disparate cardiac transplantation (bm12
      toB6) and the graft rejection was monitored. In adiponectin-null mice we observed
      that the cellular infiltrate of eosinophils, CD4(+) and CD8(+) T cells was
      reduced in grafts compared to the controls as was collagen deposition and vessel
      occlusion. A similar outcome was observed for skin transplants except that
      neutrophil infiltration was increased. Low levels of IL-4 were detected in the
      grafts and serum. The effect of adiponectin signaling on IL-4 expression was
      further investigated. Treatment with AMPK and p38 MAPK inhibitors blocked
      adiponectin enhanced T cell proliferation in mixed lymphocyte reactions.
      Inhibition of AMPK reduced eosinophil infiltration in skin grafts in wild type
      recipients and in contrast AMPK activation increased eosinophils in adiponectin
      null recipients. The addition of adiponectin increased IL-4 production by the T
      cell line EL4 with augmented nuclear GATA-3 and phospho-STAT6 expression which
      were suppressed by knockdown of adiponectin receptor 1 and 2. CONCLUSIONS: Our
      results demonstrate a direct effect of adiponectin on IL-4 expression which
      contributes to Th2 cytokine mediated rejection in mouse MHC class II
      histoincompatible transplants. These results add to our understanding of the
      interrelationship of metabolism and immune regulation and raise the possibility
      that AMPK inhibitors may be beneficial in selected types of rejection.

PMID- 23155425
TI  - Survival of Staphylococcus aureus ST398 in the human nose after artificial
      inoculation.
AB  - There is evidence that MRSA ST398 of animal origin is only capable of temporarily
      occupying the human nose, and it is therefore, often considered a poor human
      colonizer.We inoculated 16 healthy human volunteers with a mixture of the human
      MSSA strain 1036 (ST931, CC8) and the bovine MSSA strain 5062 (ST398, CC398), 7
      weeks after a treatment with mupirocin and chlorhexidine-containing soap.
      Bacterial survival was studied by follow-up cultures over 21 days. The human
      strain 1036 was eliminated faster (median 14 days; range 2-21 days) than the
      bovine strain 5062 (median 21 days; range 7-21 days) but this difference was not
      significant (p = 0.065). The bacterial loads were significantly higher for the
      bovine strain on day 7 and day 21. 4/14 volunteers (28.6%) showed elimination of
      both strains within 21 days. Of the 10 remaining volunteers, 5 showed no
      differences in bacterial counts between both strains, and in the other 5 the
      ST398 strain far outnumbered the human S. aureus strain. Within the 21 days of
      follow-up, neither human strain 1036 nor bovine strain 5062 appeared to acquire
      or lose any mobile genetic elements. In conclusion, S. aureus ST398 strain 5062
      is capable of adequately competing for a niche with a human strain and survives
      in the human nose for at least 21 days.

PMID- 23155426
TI  - Isomeric mono-, di-, and tri-bromobenzo-1H-triazoles as inhibitors of human
      protein kinase CK2alpha.
AB  - To further clarify the role of the individual bromine atoms of 4,5,6,7
      tetrabromotriazole (TBBt), a relatively selective inhibitor of protein kinase
      CK2, we have examined the inhibition (IC(50)) of human CK2alpha by the two mono-,
      the four di-, and the two tri- bromobenzotriazoles relative to that of TBBt.
      Halogenation of the central vicinal C(5)/C(6) atoms proved to be a key factor in
      enhancing inhibitory activity, in that 5,6-di-Br(2)Bt and 4,5,6-Br(3)Bt were
      almost as effective inhibitors as TBBt, notwithstanding their marked differences
      in pK(a) for dissociation of the triazole proton. The decrease in pK(a) on
      halogenation of the peripheral C(4)/C(7) atoms virtually nullifies the gain due
      to hydrophobic interactions, and does not lead to a decrease in IC(50). Molecular
      modeling of structures of complexes of the ligands with the enzyme, as well as
      QSAR analysis, pointed to a balance of hydrophobic and electrostatic interactions
      as a discriminator of inhibitory activity. The role of halogen bonding remains
      debatable, as originally noted for the crystal structure of TBBt with CK2alpha
      (pdb1j91). Finally we direct attention to the promising applicability of our
      series of well-defined halogenated benzotriazoles to studies on inhibition of
      kinases other than CK2.

PMID- 23155427
TI  - Visualizing sound emission of elephant vocalizations: evidence for two rumble
      production types.
AB  - Recent comparative data reveal that formant frequencies are cues to body size in
      animals, due to a close relationship between formant frequency spacing, vocal
      tract length and overall body size. Accordingly, intriguing morphological
      adaptations to elongate the vocal tract in order to lower formants occur in
      several species, with the size exaggeration hypothesis being proposed to justify
      most of these observations. While the elephant trunk is strongly implicated to
      account for the low formants of elephant rumbles, it is unknown whether elephants
      emit these vocalizations exclusively through the trunk, or whether the mouth is
      also involved in rumble production. In this study we used a sound visualization
      method (an acoustic camera) to record rumbles of five captive African elephants
      during spatial separation and subsequent bonding situations. Our results showed
      that the female elephants in our analysis produced two distinct types of rumble
      vocalizations based on vocal path differences: a nasally- and an orally-emitted
      rumble. Interestingly, nasal rumbles predominated during contact calling, whereas
      oral rumbles were mainly produced in bonding situations. In addition, nasal and
      oral rumbles varied considerably in their acoustic structure. In particular, the
      values of the first two formants reflected the estimated lengths of the vocal
      paths, corresponding to a vocal tract length of around 2 meters for nasal, and
      around 0.7 meters for oral rumbles. These results suggest that African elephants
      may be switching vocal paths to actively vary vocal tract length (with
      considerable variation in formants) according to context, and call for further
      research investigating the function of formant modulation in elephant
      vocalizations. Furthermore, by confirming the use of the elephant trunk in long
      distance rumble production, our findings provide an explanation for the extremely
      low formants in these calls, and may also indicate that formant lowering
      functions to increase call propagation distances in this species'.

PMID- 23155428
TI  - Angiotensin-converting enzyme 2 over-expression in the central nervous system
      reduces angiotensin-II-mediated cardiac hypertrophy.
AB  - Angiotensin-converting enzyme type 2 (ACE2) has been shown to be an important
      member of the renin angiotensin system. Previously, we observed that central ACE2
      reduces the development of hypertension following chronic angiotensin II (Ang-II)
      infusion in syn-hACE2 transgenic (SA) mice, in which the human ACE2 transgene is
      selectively targeted to neurons. To study the physiological consequences of
      central ACE2 over-expression on cardiac function and cardiac hypertrophy, SA and
      non-transgenic (NT) mice were infused with Ang-II (600 ng/kg/min, sc) for 14
      days, and cardiac function was assessed by echocardiography. Blood pressure (BP),
      hemodynamic parameters, left ventricle (LV) mass/tibia length, relative ventricle
      wall thickness (2PW/LVD), cardiomyocyte diameters and collagen deposition were
      similar (P>0.05) between NT and SA mice during saline infusion. After a 2-week
      infusion, BP was elevated in NT but not in SA mice. Although ejection fraction
      and fractional shortening were not altered, Ang-II infusion increased 2PW/LVD
      compared to saline infusion in NT mice. Interestingly, the 2PW/LVD and LV
      mass/tibia ratios were significantly lower in SA compared to NT mice at the end
      of infusion. Moreover, Ang-II infusion significantly increased arterial collagen
      deposition and cardiomyocytes diameter in NT mice but not in transgenic animals
      (P<0.05). More importantly, ACE2 over expression significantly reduced the Ang-II
      mediated increase in urine norepinephrine levels in SA compared to NT mice. The
      protective effect of ACE2 appears to involve reductions in Ang-II-mediated
      hypertension and sympathetic nerve activity.

PMID- 23155429
TI  - Neurotensin and CRH interactions augment human mast cell activation.
AB  - Stress affects immunity, but the mechanism is not known. Neurotensin (NT) and
      corticotropin-releasing hormone (CRH) are secreted under stress in various
      tissues, and have immunomodulatory actions. We had previously shown that NT
      augments the ability of CRH to increase mast cell-dependent skin vascular
      permeability in rodents. Here we show that NT triggered human mast cell
      degranulation and significantly augmented CRH-induced vascular endothelial growth
      factor (VEGF) release. Investigation of various signaling molecules indicated
      that only NF-kappaB activation was involved. These effects were blocked by
      pretreatment with the NTR antagonist SR48692. NT induced expression of CRH
      receptor-1 (CRHR-1), as shown by Western blot and FACS analysis. Interestingly,
      CRH also induced NTR gene and protein expression. These results indicate unique
      interactions among NT, CRH, and mast cells that may contribute to auto-immune and
      inflammatory diseases that worsen with stress.

PMID- 23155430
TI  - Isolation and characterization of human dental pulp derived stem cells by using
      media containing low human serum percentage as clinical grade substitutes for
      bovine serum.
AB  - Adult stem cells have been proposed as an alternative to embryonic stem cells to
      study multilineage differentiation in vitro and to use in therapy. Current
      culture media for isolation and expansion of adult stem cells require the use of
      large amounts of animal sera, but animal-derived culture reagents give rise to
      some questions due to the real possibility of infections and severe immune
      reactions. For these reasons a clinical grade substitute to animal sera is
      needed. We tested the isolation, proliferation, morphology, stemness related
      marker expression, and osteoblastic differentiation potential of Dental Pulp Stem
      Cells (DPSC) in a chemically defined medium containing a low percentage of human
      serum, 1.25%, in comparison to a medium containing 10% Fetal Bovine Serum (FBS).
      DPSCs cultured in presence of our isolation/proliferation medium added with low
      HS percentage were obtained without immune-selection methods and showed high
      uniformity in the expression of stem cell markers, proliferated at higher rate,
      and demonstrated comparable osteoblastic potential with respect to DPSCs cultured
      in 10% FBS. In this study we demonstrated that a chemically defined medium added
      with low HS percentage, derived from autologous and heterologous sources, could
      be a valid substitute to FBS-containing media and should be helpful for adult
      stem cells clinical application.

PMID- 23155431
TI  - Cardiac protection by preconditioning is generated via an iron-signal created by
      proteasomal degradation of iron proteins.
AB  - Ischemia associated injury of the myocardium is caused by oxidative damage during
      reperfusion. Myocardial protection by ischemic preconditioning (IPC) was shown to
      be mediated by a transient 'iron-signal' that leads to the accumulation of
      apoferritin and sequestration of reactive iron released during the ischemia. Here
      we identified the source of this 'iron signal' and evaluated its role in the
      mechanisms of cardiac protection by hypoxic preconditioning. Rat hearts were
      retrogradely perfused and the effect of proteasomal and lysosomal protease
      inhibitors on ferritin levels were measured. The iron-signal was abolished,
      ferritin levels were not increased and cardiac protection was diminished by
      inhibition of the proteasome prior to IPC. Similarly, double amounts of ferritin
      and better recovery after ex vivo ischemia-and-reperfusion (I/R) were found in
      hearts from in vivo hypoxia pre-conditioned animals. IPC followed by normoxic
      perfusion for 30 min ('delay') prior to I/R caused a reduced ferritin
      accumulation at the end of the ischemia phase and reduced protection. Full
      restoration of the IPC-mediated cardiac protection was achieved by employing
      lysosomal inhibitors during the 'delay'. In conclusion, proteasomal protein
      degradation of iron-proteins causes the generation of the 'iron-signal' by IPC,
      ensuing de-novo apoferritin synthesis and thus, sequestering reactive iron.
      Lysosomal proteases are involved in subsequent ferritin breakdown as revealed by
      the use of specific pathway inhibitors during the 'delay'. We suggest that
      proteasomal iron-protein degradation is a stress response causing an expeditious
      cytosolic iron release thus, altering iron homeostasis to protect the myocardium
      during I/R, while lysosomal ferritin degradation is part of housekeeping iron
      homeostasis.

PMID- 23155432
TI  - Early versus delayed insertion of intrauterine contraception after medical
      abortion - a randomized controlled trial.
AB  - BACKGROUND: Today, a large proportion of early abortions are medical
      terminations, in accordance to the woman's choice. Intrauterine contraceptives
      (IUC) provide highly effective, reversible, long-acting contraception. However,
      the effects of timing of IUC insertion after medical abortion are not known.
      METHODS: Women undergoing medical abortion with mifepristone and misoprostol up
      to 63 days gestation and opting for IUC were randomised to early insertion (day 5
      9 after mifepristone) or delayed (routine) insertion (at 3-4 weeks after
      mifepristone). The primary outcome was the rate of IUC expulsion at six months
      after IUC insertion. RESULTS: A total of 129 women were randomized, and 116 women
      had a successful IUC insertion. There was no difference in expulsion rate between
      early (9.7%) vs. delayed (7.4%) IUC insertion (risk difference -9.2-13.4).
      Furthermore, 1.5% of women randomized to early and 11.5% to delayed insertion did
      not attend the follow up (proportion difference 10.0%, 95% CI: 1.8-20.6%, p =
      0.015), and a higher proportion of women (41%) had had unprotected intercourse
      prior to returning for insertion in the delayed group compared with the early
      group (16%) (p = 0.015). Adverse events were rare and did not differ between the
      groups. CONCLUSIONS: Early insertion of IUC after medical abortion was safe and
      well tolerated with no increased incidence for expulsions or complications. Women
      were more likely to return for the IUC insertion if scheduled early after the
      abortion, and less likely to have had an unprotected intercourse prior to the IUC
      insertion. Early insertion should be offered as a routine for women undergoing
      first trimester medical abortion. TRIAL REGISTRATION: ClinicalTrials.gov
      NCT01537562.

PMID- 23155433
TI  - Identification of nitrogen starvation-responsive microRNAs in Arabidopsis
      thaliana.
AB  - microRNAs (miRNAs) are a class of negative regulators that take part in many
      processes such as growth and development, stress responses, and metabolism in
      plants. Recently, miRNAs were shown to function in plant nutrient metabolism.
      Moreover, several miRNAs were identified in the response to nitrogen (N)
      deficiency. To investigate the functions of other miRNAs in N deficiency, deep
      sequencing technology was used to detect the expression of small RNAs under N
      sufficient and -deficient conditions. The results showed that members from the
      same miRNA families displayed differential expression in response to N
      deficiency. Upon N starvation, the expression of miR169, miR171, miR395, miR397,
      miR398, miR399, miR408, miR827, and miR857 was repressed, whereas those of
      miR160, miR780, miR826, miR842, and miR846 were induced. miR826, a newly
      identified N-starvation-induced miRNA, was found to target the AOP2 gene. Among
      these N-starvation-responsive miRNAs, several were involved in cross-talk among
      responses to different nutrient (N, P, S, Cu) deficiencies. miR160, miR167, and
      miR171 could be responsible for the development of Arabidopsis root systems under
      N-starvation conditions. In addition, twenty novel miRNAs were identified and
      nine of them were significantly responsive to N-starvation. This study represents
      comprehensive expression profiling of N-starvation-responsive miRNAs and advances
      our understanding of the regulation of N homeostasis mediated by miRNAs.

PMID- 23155434
TI  - Cognitive biases toward Internet game-related pictures and executive deficits in
      individuals with an Internet game addiction.
AB  - BACKGROUND: The cue-related go/no-go switching task provides an experimental
      approach to study individual's flexibility in changing situations. Because
      Internet addiction disorder (IAD) belongs to the compulsive-impulsive spectrum of
      disorders, it should present cognitive bias and executive functioning deficit
      characteristics of some of these types of disorders. Until now, no studies have
      been reported on cognitive bias and executive function involving mental
      flexibility and response inhibition in IAD. METHODOLOGY/PRINCIPAL FINDINGS: A
      total of 46 subjects who met the criteria of the modified Young's Diagnostic
      Questionnaire for Internet addiction (YDQ) were recruited as an Internet game
      addiction (IGA) group, along with 46 healthy control individuals. All
      participants performed the Internet game-shifting task. Using hit rate, RT, d'
      and C as the dependent measures, a three-way ANOVA (group * target * condition)
      was performed. For hit rate, a significant effect of group, type of target and
      condition were found. The group-target interaction effect was significant. For
      RT, significant effects were revealed for group and type of target. The group
      target interaction effect was significant. Comparisons of the means revealed that
      the slowing down of IGA relative to NIA was more pronounced when the target
      stimuli were neutral as opposed to Internet game-related pictures. In addition,
      the group-condition interaction effect was significant. For d', significant
      effects of group, type of target and condition were found. The group-target
      interaction effect was significant. For C, the type of target produced a
      significant effect. There was a positive correlation between the length of the
      addiction (number of years) and the severity of the cognitive bias. CONCLUSIONS:
      IGA present cognitive biases towards information related to Internet gaming.
      These biases, as well as poor executive functioning skills (lower mental
      flexibility and response inhibition), might be responsible for Internet game
      addiction. The assessment of cognitive biases in IGA might provide a methodology
      for evaluation of therapeutic effects.

PMID- 23155435
TI  - Animal-borne acoustic transceivers reveal patterns of at-sea associations in an
      upper-trophic level predator.
AB  - Satellite telemetry data have substantially increased our understanding of
      habitat use and foraging behaviour of upper-trophic marine predators, but fall
      short of providing an understanding of their social behaviour. We sought to
      determine whether novel acoustic and archival GPS data could be used to examine
      at-sea associations among grey seals (Halichoerus grypus) during the fall
      foraging period. Fifteen grey seals from Sable Island, Canada were deployed with
      Vemco Mobile Transceivers and Satellite-GPS transmitters in October 2009, 13 of
      which were recaptured and units retrieved 79 +/- 2.3 days later during the
      following breeding season, December 2009-January 2010. An association between two
      individuals was defined as a cluster of acoustic detections where the time
      between detections was <30 min. Bathymetry, travel rate, and behavioural state
      (slow and fast movement) were determined for each GPS archival point (3.7 +/- 0.1
      locations recorded per hour). Behavioural state was estimated using a hidden
      Markov model. All seals had been involved in associations with other instrumented
      seals while at sea, with a total of 1,872 acoustic detections recorded in 201
      associations. The median number of detections per association was 3 (range: 1
      151) and the median duration of an association was 0.17 h (range: <0.1-11.3 h).
      Linear mixed-effects models showed that associations occurred when seals were
      exhibiting slow movement (0.24 +/- 0.01 ms(-1)) on shallow (53.4 +/- 3.7 m)
      offshore banks where dominant prey is known to occur. These results suggest the
      occurrence of short-term associations among multiple individuals at foraging
      grounds and provide new insights into the foraging ecology of this upper-trophic
      marine predator.

PMID- 23155436
TI  - Cholesterol side-chain cleavage gene expression in theca cells: augmented
      transcriptional regulation and mRNA stability in polycystic ovary syndrome.
AB  - Hyperandrogenism is characteristic of women with polycystic ovary syndrome
      (PCOS). Ovarian theca cells isolated from PCOS follicles and maintained in long
      term culture produce elevated levels of progestins and androgens compared to
      normal theca cells. Augmented steroid production in PCOS theca cells is
      associated with changes in the expression of genes for several steroidogenic
      enzymes, including CYP11A1, which encodes cytochrome P450 cholesterol side-chain
      cleavage. Here, we further examined CYP11A1 gene expression, at both the
      transcriptional and post-transcriptional level in normal and PCOS theca cells
      propagated in long-term culture utilizing quantitative RT-PCR, functional
      promoter analyses, and mRNA degradation studies. The minimal element(s) that
      conferred increased basal and cAMP-dependent CYP11A1 promoter function were
      determined. CYP11A1 mRNA half-life in normal and PCOS theca cells was compared.
      Results of these cumulative studies showed that basal and forskolin stimulated
      steady state CYP11A1 mRNA abundance and CYP11A1 promoter activity were increased
      in PCOS theca cells. Deletion analysis of the CYP11A1 promoter demonstrated that
      augmented promoter function in PCOS theca cells results from increased basal
      regulation conferred by a minimal sequence between -160 and -90 bp of the
      transcriptional start site. The transcription factor, nuclear factor 1C2, was
      observed to regulate basal activity of this minimal CYP11A1 element. Examination
      of mRNA stability in normal and PCOS theca cells demonstrated that CYP11A1 mRNA
      half-life increased >2-fold, from approximately 9.22+/-1.62 h in normal cells, to
      22.38+/-0.92 h in PCOS cells. Forskolin treatment did not prolong CYP11A1 mRNA
      stability in either normal or PCOS theca cells. The 5'-UTR of CYP11A1 mRNA
      confers increased basal mRNA stability in PCOS cells. In conclusion, these
      studies show that elevated steady state CYP11A1 mRNA abundance in PCOS cells
      results from increased transactivation of the CYP11A1 promoter and increased
      CYP11A1 mRNA stability.

PMID- 23155437
TI  - Inflamm-aging and arachadonic acid metabolite differences with stage of tendon
      disease.
AB  - The contribution of inflammation to the pathogenesis of tendinopathy and high
      prevalence of re-injury is not well established, although recent evidence
      suggests involvement of prostaglandins. We investigated the roles of
      prostaglandins and inflammation-resolving mediators in naturally occurring equine
      tendon injury with disease stage and age. Levels of prostaglandins E(2) (PGE(2)),
      F(2alpha) (PGF(2alpha)), lipoxin A(4) (LXA(4)) and its receptor FPR2/ALX were
      analysed in extracts of normal, sub-acute and chronic injured tendons. To assess
      whether potential changes were associated with altered PGE(2) metabolism,
      microsomal prostaglandin E synthase-1 (mPGES-1), prostaglandin dehydrogenase
      (PGDH), COX-2 and EP(4) receptor expression were investigated. The ability of
      tendons to resolve inflammation was determined by assessing FPR2/ALX expression
      in natural injury and IL-1beta stimulated tendon explants.Alterations in the
      profile of lipid mediators during sub-acute injury included low PGE(2) and
      elevated LXA(4) levels compared to normal and chronic injuries. In contrast,
      PGF(2alpha) levels remained unchanged and were three-fold lower than PGE(2). The
      synthetic capacity of PGE(2) as measured by the ratio of mPGES-1:PGDH was
      elevated in sub-acute injury, suggesting aberrations in tendon prostaglandin
      metabolism, whilst COX-2 and EP(4) receptor were unchanged. Paradoxically low
      tendon PGE(2) levels in early injury may be attributed to increased local
      clearance via PGDH or the class switching of lipid mediators from the
      prostaglandin to the lipoxin axis. PGE(2) is therefore implicated in the
      development of tendon inflammation and its ensuing resolution. Whilst there was
      no relationship between age and tendon LXA(4) levels, there was an age-associated
      decline in FPR2/ALX receptor expression with concurrent increased PGE(2) levels
      in injury. Furthermore, uninjured tendon explants from younger (<10 years) but
      not older horses (>=10 years) treated with IL-1beta responded by increasing
      FPR2/ALX suggesting aged individuals exhibit a reduced capacity to resolve
      inflammation via FPR2/ALX, which may present a potential mechanism for
      development of chronic tendinopathy and re-injury.

PMID- 23155439
TI  - Kretzoiarctos gen. nov., the oldest member of the giant panda clade.
AB  - The phylogenetic position of the giant panda, Ailuropoda melanoleuca (Carnivora:
      Ursidae: Ailuropodinae), has been one of the most hotly debated topics by
      mammalian biologists and paleontologists during the last century. Based on
      molecular data, it is currently recognized as a true ursid, sister-taxon of the
      remaining extant bears, from which it would have diverged by the Early Miocene.
      However, from a paleobiogeographic and chronological perspective, the origin of
      the giant panda lineage has remained elusive due to the scarcity of the available
      Miocene fossil record. Until recently, the genus Ailurarctos from the Late
      Miocene of China (ca. 8-7 mya) was recognized as the oldest undoubted member of
      the Ailuropodinae, suggesting that the panda lineage might have originated from
      an Ursavus ancestor. The role of the purported ailuropodine Agriarctos, from the
      Miocene of Europe, in the origins of this clade has been generally dismissed due
      to the paucity of the available material. Here, we describe a new ailuropodine
      genus, Kretzoiarctos gen. nov., based on remains from two Middle Miocene (ca. 12
      11 Ma) Spanish localities. A cladistic analysis of fossil and extant members of
      the Ursoidea confirms the inclusion of the new genus into the Ailuropodinae.
      Moreover, Kretzoiarctos precedes in time the previously-known, Late Miocene
      members of the giant panda clade from Eurasia (Agriarctos and Ailurarctos). The
      former can be therefore considered the oldest recorded member of the giant panda
      lineage, which has significant implications for understanding the origins of this
      clade from a paleobiogeographic viewpoint.

PMID- 23155438
TI  - Genetic overlap between apparently sporadic motor neuron diseases.
AB  - Progressive muscular atrophy (PMA) and amyotrophic lateral sclerosis (ALS) are
      devastating motor neuron diseases (MNDs), which result in muscle weakness and/or
      spasticity. We compared mutation frequencies in genes known to be associated with
      MNDs between patients with apparently sporadic PMA and ALS. A total of 261
      patients with adult-onset sporadic PMA, patients with sporadic ALS, and control
      subjects of Dutch descent were obtained at national referral centers for
      neuromuscular diseases in The Netherlands. Sanger sequencing was used to screen
      these subjects for mutations in the coding regions of superoxide dismutase-1
      (SOD1), angiogenin (ANG), fused in sarcoma/translated in liposarcoma (FUS/TLS),
      TAR DNA-binding protein 43 (TARDBP), and multivesicular body protein 2B (CHMP2B).
      In our cohort of PMA patients we identified two SOD1 mutations (p.D90A, p.I113T),
      one ANG mutation (p.K17I), one FUS/TLS mutation (p.R521H), one TARDBP mutation
      (p.N352S), and one novel CHMP2B mutation (p.R69Q). The mutation frequency of
      these genes was similar in sporadic PMA (2.7%) and ALS (2.0%) patients, and
      therefore, our findings demonstrate a genetic overlap between apparently sporadic
      PMA and ALS.

PMID- 23155440
TI  - A novel two-component system involved in secretion stress response in
      Streptomyces lividans.
AB  - BACKGROUND: Misfolded proteins accumulating outside the bacterial cytoplasmic
      membrane can interfere with the secretory machinery, hence the existence of
      quality factors to eliminate these misfolded proteins is of capital importance in
      bacteria that are efficient producers of secretory proteins. These bacteria
      normally use a specific two-component system to respond to the stress produced by
      the accumulation of the misfolded proteins, by activating the expression of HtrA
      like proteases to specifically eliminate the incorrectly folded proteins.
      METHODOLOGY/PRINCIPAL FINDINGS: Overproduction of alpha-amylase in S. lividans
      causing secretion stress permitted the identification of a two-component system
      (SCO4156-SCO4155) that regulates three HtrA-like proteases which appear to be
      involved in secretion stress response. Mutants in each of the genes forming part
      of the two-genes operon that encodes the sensor and regulator protein components
      accumulated misfolded proteins outside the cell, strongly suggesting the
      involvement of this two-component system in the S. lividans secretion stress
      response. CONCLUSIONS/SIGNIFICANCE: To our knowledge this is the first time that
      a specific secretion stress response two-component system is found to control the
      expression of three HtrA-like protease genes in S. lividans, a bacterium that has
      been repeatedly used as a host for the synthesis of homologous and heterologous
      secretory proteins of industrial application.

PMID- 23155441
TI  - Cancer risk of anti-TNF-alpha at recommended doses in adult rheumatoid arthritis:
      a meta-analysis with intention to treat and per protocol analyses.
AB  - BACKGROUND: The risk of malignancies on TNF-alpha antagonists is controversial.
      The aim of this survey was to assess cancer risk on TNF-alpha antagonists in
      adult rheumatoid arthritis patients, including the five marketed drugs
      (infliximab, etanercept, adalimumab, golimumab and certolizumab) used in line
      with the New Drug Application. Furthermore, the relative interest of modified
      intention to treat or per protocol analyses to assess such sparse events remains
      unknown. METHODOLOGY/PRINCIPAL FINDINGS: Data sources were MEDLINE, CENTRAL, ISI
      Web of Science, ACR and EULAR meeting abstracts, scientific evaluation of the
      drugs leading to their marketing approval, and clinicaltrials.gov, until 31
      December 2012.We selected double-blind randomized controlled trials in adult
      rheumatoid arthritis patients, including at least one treatment arm in line with
      New Drug Application. We performed random effect meta-analysis, with modified
      intention to treat and per protocol analyses. Thirty-three trials were included.
      There was no excess risk of malignancies on anti-TNF-alpha administered in line
      with New Drug Application in the per protocol model (OR, 0.93 95%CI[0.59-1.44]),
      as well as in the modified intention to treat model (OR, 1.27 95%CI[0.82-1.98]).
      There was a non-significant tendency for an excess non-melanoma skin cancer risk
      in both models (respectively, 1.37 [0.71-2.66] and 1.90 [0.98-3.67]). With fixed
      effect Peto model restricting to trials during at least 52 weeks, the overall
      cancer risk was respectively 1.60 [0.97-2.64] and 1.22 [0.72-2.08]. Whatever the
      model, modified intention to treat analysis led to higher estimations than per
      protocol analysis. The later may underestimate the treatment effect when
      assessing very sparse events and when many patients dropped out in placebo arms.
      In metaregression, there was no differential risk among the five drugs.
      CONCLUSIONS/SIGNIFICANCE: This study did not find any evidence for an excess
      cancer risk on TNF-alpha antagonists in adult rheumatoid arthritis patients, but
      an excess cancer risk after several years of exposure cannot be ruled out. Both
      modified intention to treat and per protocol analyses should be presented in such
      safety analyses.

PMID- 23155442
TI  - Cross-species functional genomic analysis identifies resistance genes of the
      histone deacetylase inhibitor valproic acid.
AB  - The mechanisms of successful epigenetic reprogramming in cancer are not well
      characterized as they involve coordinated removal of repressive marks and
      deposition of activating marks by a large number of histone and DNA modification
      enzymes. Here, we have used a cross-species functional genomic approach to
      identify conserved genetic interactions to improve therapeutic effect of the
      histone deacetylase inhibitor (HDACi) valproic acid, which increases survival in
      more than 20% of patients with advanced acute myeloid leukemia (AML). Using a
      bidirectional synthetic lethality screen revealing genes that increased or
      decreased VPA sensitivity in C. elegans, we identified novel conserved
      sensitizers and synthetic lethal interactors of VPA. One sensitizer identified as
      a conserved determinant of therapeutic success of HDACi was UTX (KDM6A), which
      demonstrates a functional relationship between protein acetylation and lysine
      specific methylation. The synthetic lethal screen identified resistance programs
      that compensated for the HDACi-induced global hyper-acetylation, and confirmed
      MAPKAPK2, HSP90AA1, HSP90AB1 and ACTB as conserved hubs in a resistance program
      for HDACi that are drugable in human AML cell lines. Hence, these resistance hubs
      represent promising novel targets for refinement of combinatorial epigenetic anti
      cancer therapy.

PMID- 23155443
TI  - Dynamics of intraocular IFN-gamma, IL-17 and IL-10-producing cell populations
      during relapsing and monophasic rat experimental autoimmune uveitis.
AB  - A major limitation of most animal models of autoimmune diseases is that they do
      not reproduce the chronic or relapsing-remitting pattern characteristic of many
      human autoimmune diseases. This problem has been overcome in our rat models of
      experimentally induced monophasic or relapsing-remitting autoimmune uveitis
      (EAU), which depend on the inducing antigen peptides from retinal S-Antigen
      (monophasic EAU) or interphotoreceptor retinoid-binding protein (relapsing EAU).
      These models enable us to compare autoreactive and regulatory T cell populations.
      Intraocular, but not peripheral T cells differ in their cytokine profiles (IFN
      gamma, IL-17 and IL-10) at distinct time points during monophasic or relapsing
      EAU. Only intraocular T cells concomitantly produced IFN-gamma, IL-17 and/or IL
      10. Monophasic EAU presented rising numbers of cells expressing IFN-gamma and IL
      17 (Th1/Th17) and cells expressing IL-10 or Foxp3. During relapsing uveitis an
      increase of intraocular IFN-gamma+ cells and a concomitant decrease of IL-17+
      cells was detected, while IL-10+ populations remained stable. Foxp3+ cells and
      cells expressing IL-10, even in combination with IFN-gamma or IL-17, increased
      during the resolution of monophasic EAU, suggesting a regulatory role for these T
      cells. In general, cells producing multiple cytokines increased in monophasic and
      decreased in relapsing EAU. The distinct appearance of certain intraocular
      populations with characteristics of regulatory cells points to a differential
      influence of the ocular environment on T cells that induce acute and monophasic
      or relapsing disease. Here we provide evidence that different autoantigens can
      elicit distinct and differently regulated immune responses. IFN-gamma, but not IL
      17 seems to be the key player in relapsing-remitting uveitis, as shown by
      increased, synchronized relapses after intraocular application of IFN-gamma. We
      demonstrated dynamic changes of the cytokine pattern during monophasic and
      relapsing-remitting disease with strongly increasing IL-10 expression in
      intraocular T cells during monophasic uveitis.

PMID- 23155444
TI  - Please don't! The automatic extrapolation of dangerous intentions.
AB  - Facial emotions and emotional body postures can easily grab attention in social
      communication. In the context of faces, gaze has been shown as an important cue
      for orienting attention, but less is known for other important body parts such as
      hands. In the present study we investigated whether hands may orient attention
      due to the emotional features they convey. By implying motion in static
      photographs of hands, we aimed at furnishing observers with information about the
      intention to act and at testing if this interacted with the hand automatic
      coding. In this study, we compared neutral and frontal hands to emotionally
      threatening hands, rotated along their radial-ulnar axes in a Sidedness task (a
      Simon-like task based on automatic access to body representation). Results showed
      a Sidedness effect for both the palm and the back views with either neutral and
      emotional hands. More important, no difference was found between the two views
      for neutral hands, but it emerged in the case of the emotional hands: faster
      reaction times were found for the palm than the back view. The difference was
      ascribed to palm views' "offensive" pose: a source of threat that might have
      raised participants' arousal. This hypothesis was also supported by conscious
      evaluations of the dimensions of valence (pleasant-unpleasant) and arousal.
      Results are discussed in light of emotional feature coding.

PMID- 23155445
TI  - Purkinje cell maturation participates in the control of oligodendrocyte
      differentiation: role of sonic hedgehog and vitronectin.
AB  - Oligodendrocyte differentiation is temporally regulated during development by
      multiple factors. Here, we investigated whether the timing of oligodendrocyte
      differentiation might be controlled by neuronal differentiation in cerebellar
      organotypic cultures. In these cultures, the slices taken from newborn mice show
      very few oligodendrocytes during the first week of culture (immature slices)
      whereas their number increases importantly during the second week (mature
      slices). First, we showed that mature cerebellar slices or their conditioned
      media stimulated oligodendrocyte differentiation in immature slices thus
      demonstrating the existence of diffusible factors controlling oligodendrocyte
      differentiation. Using conditioned media from different models of slice culture
      in which the number of Purkinje cells varies drastically, we showed that the
      effects of these differentiating factors were proportional to the number of
      Purkinje cells. To identify these diffusible factors, we first performed a
      transcriptome analysis with an Affymetrix array for cerebellar cortex and then
      real-time quantitative PCR on mRNAs extracted from fluorescent flow cytometry
      sorted (FACS) Purkinje cells of L7-GFP transgenic mice at different ages. These
      analyses revealed that during postnatal maturation, Purkinje cells down-regulate
      Sonic Hedgehog and up-regulate vitronectin. Then, we showed that Sonic Hedgehog
      stimulates the proliferation of oligodendrocyte precursor cells and inhibits
      their differentiation. In contrast, vitronectin stimulates oligodendrocyte
      differentiation, whereas its inhibition with blocking antibodies abolishes the
      conditioned media effects. Altogether, these results suggest that Purkinje cells
      participate in controlling the timing of oligodendrocyte differentiation in the
      cerebellum through the developmentally regulated expression of diffusible
      molecules such as Sonic Hedgehog and vitronectin.

PMID- 23155447
TI  - Barley HvHMA1 is a heavy metal pump involved in mobilizing organellar Zn and Cu
      and plays a role in metal loading into grains.
AB  - Heavy metal transporters belonging to the P(1B)-ATPase subfamily of P-type
      ATPases are key players in cellular heavy metal homeostasis. Heavy metal
      transporters belonging to the P(1B)-ATPase subfamily of P-type ATPases are key
      players in cellular heavy metal homeostasis. In this study we investigated the
      properties of HvHMA1, which is a barley orthologue of Arabidopsis thaliana AtHMA1
      localized to the chloroplast envelope. HvHMA1 was localized to the periphery of
      chloroplast of leaves and in intracellular compartments of grain aleurone cells.
      HvHMA1 expression was significantly higher in grains compared to leaves. In
      leaves, HvHMA1 expression was moderately induced by Zn deficiency, but reduced by
      toxic levels of Zn, Cu and Cd. Isolated barley chloroplasts exported Zn and Cu
      when supplied with Mg-ATP and this transport was inhibited by the AtHMA1
      inhibitor thapsigargin. Down-regulation of HvHMA1 by RNA interference did not
      have an effect on foliar Zn and Cu contents but resulted in a significant
      increase in grain Zn and Cu content. Heterologous expression of HvHMA1 in heavy
      metal-sensitive yeast strains increased their sensitivity to Zn, but also to Cu,
      Co, Cd, Ca, Mn, and Fe. Based on these results, we suggest that HvHMA1 is a broad
      specificity exporter of metals from chloroplasts and serve as a scavenging
      mechanism for mobilizing plastid Zn and Cu when cells become deficient in these
      elements. In grains, HvHMA1 might be involved in mobilizing Zn and Cu from the
      aleurone cells during grain filling and germination.

PMID- 23155446
TI  - Interaction of inflammation and hyperoxia in a rat model of neonatal white matter
      damage.
AB  - Intrauterine infection and inflammation are major reasons for preterm birth. The
      switch from placenta-mediated to lung-mediated oxygen supply during birth is
      associated with a sudden rise of tissue oxygen tension that amounts to relative
      hyperoxia in preterm infants. Both infection/inflammation and hyperoxia have been
      shown to be involved in brain injury of preterm infants. Hypothesizing that they
      might be additive or synergistic, we investigated the influence of a systemic
      lipopolysaccharide (LPS) application on hyperoxia-induced white matter damage
      (WMD) in newborn rats. Three-day-old Wistar rat pups received 0.25 mg/kg LPS i.p.
      and were subjected to 80% oxygen on P6 for 24 h. The extent of WMD was assessed
      by immunohistochemistry, western blots, and diffusion tensor (DT) magnetic
      resonance imaging (MRI). In addition, the effects of LPS and hyperoxia were
      studied in an in vitro co-culture system of primary rat oligodendrocytes and
      microglia cells. Both noxious stimuli, hyperoxia, and LPS caused hypomyelination
      as revealed by western blot, immunohistochemistry, and altered WM microstructure
      on DT-MRI. Even so, cellular changes resulting in hypomyelination seem to be
      different. While hyperoxia induces cell death, LPS induces oligodendrocyte
      maturity arrest without cell death as revealed by TUNEL-staining and
      immunohistological maturation analysis. In the two-hit scenario cell death is
      reduced compared with hyperoxia treated animals, nevertheless white matter
      alterations persist. Concordantly with these in vivo findings we demonstrate that
      LPS pre-incubation reduced premyelinating-oligodendrocyte susceptibility towards
      hyperoxia in vitro. This protective effect might be caused by upregulation of
      interleukin-10 and superoxide dismutase expression after LPS stimulation. Reduced
      expression of transcription factors controlling oligodendrocyte development and
      maturation further indicates oligodendrocyte maturity arrest. The knowledge about
      mechanisms that triggered hypomyelination contributes to a better understanding
      of WMD in premature born infants.

PMID- 23155448
TI  - The association between four genetic variants in microRNAs (rs11614913,
      rs2910164, rs3746444, rs2292832) and cancer risk: evidence from published
      studies.
AB  - MicroRNAs (miRNAs) participate in diverse biological pathways and may act as
      either tumor suppressor genes or oncogenes. Single nucleotide polymorphisms
      (SNPs) in miRNA may contribute to cancer development with changes in the
      microRNA's properties and/or maturation. Polymorphisms in miRNAs have been
      suggested in predisposition to cancer risk; however, accumulated studies have
      shown inconsistent conslusionss. To further validate determine whether there is
      any potential association between the four common SNPs (miR-196a2C>T, rs11614913;
      miR-146aG>C, rs2910164; miR-499A>G, rs3746444; miR-149C>T, rs2292832) and the
      risk for developing risk, a meta-analysis was performed according to the 40
      published case-control studies. Odds ratios (ORs) with 95% confidence intervals
      (CIs) were calculated to assess the extent of the association. The results
      demonstrated that the rs11614913TT genotype was significantly associated with a
      decreased cancer risk, in particular with a decreased risk for colorectal cancer
      and lung cancer, or for Asian population subgroup. In addition, the rs2910164C
      allele was associated with decreased risk for esophageal cancer, cervical cancer,
      prostate cancer, and hepatocellular carcinoma (HCC), in particular in Asian
      population subgroup. Similarly, the rs3746444G allele was observed as a risk
      factor for cancers in the Asian population. It is concluded that two SNPs prsent
      in miRNAs(rs11614913TT, and rs2910164C) may protect against the pathogenesis of
      some cancers, and that the rs3746444 may increase risk for cancer.

PMID- 23155449
TI  - Probing mixed-genotype infections I: extraction and cloning of infections from
      hosts of the trypanosomatid Crithidia bombi.
AB  - We here present an efficient, precise and reliable method to isolate and
      cultivate healthy and viable single Crithidia bombi cells from bumblebee faeces
      using flow cytometry. We report a precision of >99% in obtaining single
      trypanosomatid cells for further culture and analysis ("cloning"). In the study,
      we have investigated the use of different liquid media to cultivate C. bombi and
      present an optimal medium for obtaining viable clones from all tested, infected
      host donors. We show that this method can be applied to genotype a collection of
      clones from natural infections. Furthermore, we show how to cryo-preserve C.
      bombi cells to be revived to become infective clones after at least 4 years of
      storage. Considering the high prevalence of infections in natural populations,
      our method provides a powerful tool in studying the level and diversity of these
      infections, and thus enriches the current methodology for the studies of complex
      host-parasite interactions.

PMID- 23155450
TI  - Effect of intentional bias on agency attribution of animated motion: an event
      related fMRI study.
AB  - Animated movements of simple geometric shapes can readily be interpreted as
      depicting social events in which animate agents are engaged in intentional
      activity. However, the brain regions associated with such intention have not been
      clearly elucidated. In this study, intentional bias was manipulated using shape
      and pattern animations while measuring associated brain activity using event
      related functional magnetic resonance imaging (fMRI). Twenty-five higher
      intention involved and twenty-five lower-intention involved animations were
      presented to participants. Behavioral results showed that the degree of agency
      attribution of the mental state increased as intentional involvement increased.
      fMRI results revealed that the posterior superior temporal sulcus (STS), inferior
      temporal gyrus (ITG), inferior frontal gyrus (IFG), premotor, temporal pole,
      supramarginal gyrus, and superior parietal lobule (SPL) were activated while
      participants viewed the high-intention animations. In contrast, occipital,
      lingual, and middle frontal gyri were activated while the participants viewed the
      low-intention animations. These findings suggest that as agent attribution
      increases, the visual brain changes its functional role to the intentional brain
      and becomes a flexible network for processing information about social
      interaction.

PMID- 23155451
TI  - Genetic footprints of Iberian cattle in America 500 years after the arrival of
      Columbus.
AB  - BACKGROUND: American Creole cattle presumably descend from animals imported from
      the Iberian Peninsula during the period of colonization and settlement, through
      different migration routes, and may have also suffered the influence of cattle
      directly imported from Africa. The introduction of European cattle, which began
      in the 18th century, and later of Zebu from India, has threatened the survival of
      Creole populations, some of which have nearly disappeared or were admixed with
      exotic breeds. Assessment of the genetic status of Creole cattle is essential for
      the establishment of conservation programs of these historical resources.
      METHODOLOGY/PRINCIPAL FINDINGS: We sampled 27 Creole populations, 39 Iberian, 9
      European and 6 Zebu breeds. We used microsatellite markers to assess the origins
      of Creole cattle, and to investigate the influence of different breeds on their
      genetic make-up. The major ancestral contributions are from breeds of southern
      Spain and Portugal, in agreement with the historical ports of departure of ships
      sailing towards the Western Hemisphere. This Iberian contribution to Creoles may
      also include some African influence, given the influential role that African
      cattle have had in the development of Iberian breeds, but the possibility of a
      direct influence on Creoles of African cattle imported to America can not be
      discarded. In addition to the Iberian influence, the admixture with other
      European breeds was minor. The Creoles from tropical areas, especially those from
      the Caribbean, show clear signs of admixture with Zebu. CONCLUSIONS/SIGNIFICANCE:
      Nearly five centuries since cattle were first brought to the Americas, Creoles
      still show a strong and predominant signature of their Iberian ancestors. Creole
      breeds differ widely from each other, both in genetic structure and influences
      from other breeds. Efforts are needed to avoid their extinction or further
      genetic erosion, which would compromise centuries of selective adaptation to a
      wide range of environmental conditions.

PMID- 23155452
TI  - Physiological responses in relation to performance during competition in elite
      synchronized swimmers.
AB  - PURPOSE: We aimed to characterize the cardiovascular, lactate and perceived
      exertion responses in relation to performance during competition in junior and
      senior elite synchronized swimmers. METHODS: 34 high level senior (21.4 +/- 3.6
      years) and junior (15.9 +/- 1.0) synchronized swimmers were monitored while
      performing a total of 96 routines during an official national championship in the
      technical and free solo, duet and team competitive programs. Heart rate was
      continuously monitored. Peak blood lactate was obtained from serial capillary
      samples during recovery. Post-exercise rate of perceived exertion was assessed
      using the Borg CR-10 scale. Total competition scores were obtained from official
      records. RESULTS: Data collection was complete in 54 cases. Pre-exercise mean
      heart rate (beats.min(-1)) was 129.1 +/- 13.1, and quickly increased during the
      exercise to attain mean peak values of 191.7 +/- 8.7, with interspersed
      bradycardic events down to 88.8 +/- 28.5. Mean peak blood lactate (mmol.L(-1))
      was highest in the free solo (8.5 +/- 1.8) and free duet (7.6 +/- 1.8) and lowest
      at the free team (6.2 +/- 1.9). Mean RPE (0-10+) was higher in juniors (7.8 +/-
      0.9) than in seniors (7.1 +/- 1.4). Multivariate analysis revealed that heart
      rate before and minimum heart rate during the routine predicted 26% of
      variability in final total score. CONCLUSIONS: Cardiovascular responses during
      competition are characterized by intense anticipatory pre-activation and rapidly
      developing tachycardia up to maximal levels with interspersed periods of marked
      bradycardia during the exercise bouts performed in apnea. Moderate blood lactate
      accumulation suggests an adaptive metabolic response as a result of the specific
      training adaptations attributed to influence of the diving response in
      synchronized swimmers. Competitive routines are perceived as very to extremely
      intense, particularly in the free solo and duets. The magnitude of anticipatory
      heart rate activation and bradycardic response appear to be related to
      performance variability.

PMID- 23155453
TI  - Reduced neonatal mortality in Meishan piglets: a role for hepatic fatty acids?
AB  - The Meishan pig breed exhibits increased prolificacy and reduced neonatal
      mortality compared to commercial breeds, such as the Large White, prompting
      breeders to introduce the Meishan genotype into commercial herds. Commercial
      piglets are highly susceptible to hypoglycemia, hypothermia, and death,
      potentially due to limited lipid stores and/or delayed hepatic metabolic ability.
      We therefore hypothesized that variation in hepatic development and lipid
      metabolism could contribute to the differences in neonatal mortality between
      breeds. Liver samples were obtained from piglets of each breed on days 0, 7, and
      21 of postnatal age and subjected to molecular and biochemical analysis. At
      birth, both breeds exhibited similar hepatic glycogen contents, despite Meishan
      piglets having significantly lower body weight. The livers from newborn Meishan
      piglets exhibited increased C18?1n9C and C20?1n9 but lower C18?0, C20?4n6, and
      C22?6n3 fatty acid content. Furthermore, by using an unsupervised machine
      learning approach, we detected an interaction between C18?1n9C and glycogen
      content in newborn Meishan piglets. Bioinformatic analysis could identify unique
      age-based clusters from the lipid profiles in Meishan piglets that were not
      apparent in the commercial offspring. Examination of the fatty acid signature
      during the neonatal period provides novel insights into the body composition of
      Meishan piglets that may facilitate liver responses that prevent hypoglycaemia
      and reduce offspring mortality.

PMID- 23155454
TI  - ERMO3/MVP1/GOLD36 is involved in a cell type-specific mechanism for maintaining
      ER morphology in Arabidopsis thaliana.
AB  - The endoplasmic reticulum (ER) has a unique, network-like morphology. The ER
      structures are composed of tubules, cisternae, and three-way junctions. This
      morphology is highly conserved among eukaryotes, but the molecular mechanism that
      maintains ER morphology has not yet been elucidated. In addition, certain
      Brassicaceae plants develop a unique ER-derived organelle called the ER body.
      This organelle accumulates large amounts of PYK10, a beta-glucosidase, but its
      physiological functions are still obscure. We aimed to identify a novel factor
      required for maintaining the morphology of the ER, including ER bodies, and
      employed a forward-genetic approach using transgenic Arabidopsis thaliana (GFP-h)
      with fluorescently-labeled ER. We isolated and investigated a mutant (designated
      endoplasmic reticulum morphology3, ermo3) with huge aggregates and abnormal
      punctate structures of ER. ERMO3 encodes a GDSL-lipase/esterase family protein,
      also known as MVP1. Here, we showed that, although ERMO3/MVP1/GOLD36 was
      expressed ubiquitously, the morphological defects of ermo3 were specifically seen
      in a certain type of cells where ER bodies developed. Coimmunoprecipitation
      analysis combined with mass spectrometry revealed that ERMO3/MVP1/GOLD36
      interacts with the PYK10 complex, a huge protein complex that is thought to be
      important for ER body-related defense systems. We also found that the depletion
      of transcription factor NAI1, a master regulator for ER body formation,
      suppressed the formation of ER-aggregates in ermo3 cells, suggesting that NAI1
      expression plays an important role in the abnormal aggregation of ER. Our results
      suggest that ERMO3/MVP1/GOLD36 is required for preventing ER and other organelles
      from abnormal aggregation and for maintaining proper ER morphology in a
      coordinated manner with NAI1.

PMID- 23155455
TI  - Genome-wide expression analysis in Down syndrome: insight into immunodeficiency.
AB  - Down syndrome (DS) is caused by triplication of Human chromosome 21 (Hsa21) and
      associated with an array of deleterious phenotypes, including mental retardation,
      heart defects and immunodeficiency. Genome-wide expression patterns of uncultured
      peripheral blood cells are useful to understanding of DS-associated immune
      dysfunction. We used a Human Exon microarray to characterize gene expression in
      uncultured peripheral blood cells derived from DS individuals and age-matched
      controls from two age groups: neonate (N) and child (C). A total of 174
      transcript clusters (gene-level) with eight located on Hsa21 in N group and 383
      transcript clusters including 56 on Hsa21 in C group were significantly
      dysregulated in DS individuals. Microarray data were validated by quantitative
      polymerase chain reaction. Functional analysis revealed that the dysregulated
      genes in DS were significantly enriched in two and six KEGG pathways in N and C
      group, respectively. These pathways included leukocyte trans-endothelial
      migration, B cell receptor signaling pathway and primary immunodeficiency, etc.,
      which causally implicated dysfunctional immunity in DS. Our results provided a
      comprehensive picture of gene expression patterns in DS at the two developmental
      stages and pointed towards candidate genes and molecular pathways potentially
      associated with the immune dysfunction in DS.

PMID- 23155456
TI  - FTO at rs9939609, food responsiveness, emotional control and symptoms of ADHD in
      preschool children.
AB  - The FTO minor allele at rs9939609 has been associated with body mass index (BMI:
      weight (kg)/height (m)(2)) in children from 5 years onwards, food intake, and
      eating behaviour. The high expression of FTO in the brain suggests that this gene
      may also be associated with behavioural phenotypes, such as impulsivity and
      control. We examined the effect of the FTO minor allele (A) at rs9939609 on
      eating behaviour, impulsivity and control in young children, thus before the BMI
      effect becomes apparent. This study was embedded in the Generation R Study, a
      population-based cohort from fetal life onwards. 1,718 children of European
      descent were genotyped for FTO at rs9939609. With logistic regression assuming an
      additive genetic model, we examined the association between the FTO minor allele
      and eating behaviour, impulsivity and control in preschool children. There was no
      relation between FTO at rs9939609 and child BMI at this age. The A allele at
      rs9939609 was associated with increased food responsiveness (OR 1.21, p = 0.03).
      Also, children with the A allele were less likely to have symptoms of ADHD (OR
      0.74, p = 0.01) and showed more emotional control (OR 0.64, p = 0.01) compared to
      children without the A allele. Our findings suggest that before the association
      between FTO and BMI becomes apparent, the FTO minor allele at rs9939609 leads to
      increased food responsiveness, a decreased risk for symptoms of ADHD and better
      emotional control. Future studies are needed to investigate whether these
      findings represent one single mechanism or reflect pleiotropic effects of FTO.

PMID- 23155457
TI  - High-throughput microRNA (miRNAs) arrays unravel the prognostic role of MiR-211
      in pancreatic cancer.
AB  - BACKGROUND: Only a subset of radically resected pancreatic ductal adenocarcinoma
      (PDAC) patients benefit from chemotherapy, and identification of prognostic
      factors is warranted. Recently miRNAs emerged as diagnostic biomarkers and
      innovative therapeutic targets, while high-throughput arrays are opening new
      opportunities to evaluate whether they can predict clinical outcome. The present
      study evaluated whether comprehensive miRNA expression profiling correlated with
      overall survival (OS) in resected PDAC patients. METHODOLOGY/PRINCIPAL FINDINGS:
      High-resolution miRNA profiles were obtained with the Toray's 3D-GeneTM-miRNA
      chip, detecting more than 1200 human miRNAs. RNA was successfully isolated from
      paraffin-embedded primary tumors of 19 out of 26 stage-pT3N1 homogeneously
      treated patients (adjuvant gemcitabine 1000 mg/m(2)/day, days-1/8/15, every 28
      days), carefully selected according to their outcome (OS<12 (N = 13) vs. OS>30
      months (N = 6), i.e. short/long-OS). Highly stringent statistics included t-test,
      distance matrix with Spearman-ranked correlation, and iterative approaches.
      Unsupervised hierarchical analysis revealed that PDACs clustered according to
      their short/long-OS classification, while the feature selection algorithm RELIEF
      identified the top 4 discriminating miRNAs between the two groups. These miRNAs
      target more than 1500 transcripts, including 169 targeted by two or more. MiR-211
      emerged as the best discriminating miRNA, with significantly higher expression in
      long- vs. short-OS patients. The expression of this miRNA was subsequently
      assessed by quantitative-PCR in an independent cohort of laser-microdissected
      PDACs from 60 resected patients treated with the same gemcitabine regimen.
      Patients with low miR-211 expression according to median value had a
      significantly shorter median OS (14.8, 95%CI = 13.1-16.5, vs. 25.7 months, 95%CI
      = 16.2-35.1, log-rank-P = 0.004). Multivariate analysis demonstrated that low miR
      211 expression was an independent factor of poor prognosis (hazard ratio 2.3, P =
      0.03) after adjusting for all the factors influencing outcome.
      CONCLUSIONS/SIGNIFICANCE: Through comprehensive microarray analysis and PCR
      validation we identified miR-211 as a prognostic factor in resected PDAC. These
      results prompt further prospective studies and research on the biological role of
      miR-211 in PDAC.

PMID- 23155458
TI  - Fertilization is not a new beginning: the relationship between sperm longevity
      and offspring performance.
AB  - Sperm are the most diverse cell type known: varying not only among- and within-
      species, but also among- and within-ejaculates of a single male. Recently, the
      causes and consequences of variability in sperm phenotypes have received much
      attention, but the importance of within-ejaculate variability remains largely
      unknown. Correlative evidence suggests that reduced within-ejaculate variation in
      sperm phenotype increases a male's fertilization success in competitive
      conditions; but the transgenerational consequences of within-ejaculate variation
      in sperm phenotype remain relatively unexplored. Here we examine the relationship
      between sperm longevity and offspring performance in a marine invertebrate with
      external fertilization, Styela plicata. Offspring sired by longer-lived sperm had
      higher performance compared to offspring sired by freshly-extracted sperm of the
      same ejaculate, both in the laboratory and the field. This indicates that within
      ejaculate differences in sperm longevity can influence offspring fitness - a
      source of variability in offspring phenotypes that has not previously been
      considered. Links between sperm phenotype and offspring performance may constrain
      responses to selection on either sperm or offspring traits, with broad ecological
      and evolutionary implications.

PMID- 23155459
TI  - A sex difference in the predisposition for physical competition: males play
      sports much more than females even in the contemporary U.S.
AB  - Much evidence indicates that men experienced an evolutionary history of physical
      competition, both one-on-one and in coalitions. We thus hypothesized that,
      compared to girls and women, boys and men will possess a greater motivational
      predisposition to be interested in sports, especially team sports. According to
      most scholars, advocacy groups, and the United States courts, however, this
      hypothesis is challenged by modest sex differences in organized school sports
      participation in the contemporary U.S., where females comprise 42% of high school
      participants and 43% of intercollegiate participants. We conducted three studies
      to test whether organized school sports participation data underestimate the
      actual sex difference in sports participation. Study 1 analyzed the American Time
      Use Survey, which interviewed 112,000 individuals regarding their activities
      during one day. Females accounted for 51% of exercise (i.e., non-competitive)
      participations, 24% of total sports participations, and 20% of team sports
      participations. These sex differences were similar for older and younger age
      groups. Study 2 was based on systematic observations of sports and exercise at 41
      public parks in four states. Females accounted for 37% of exercise
      participations, 19% of individual sports participations, and 10% of team sports
      participations. Study 3 involved surveying colleges and universities about
      intramural sports, which primarily consist of undergraduate participation in team
      sports. Across 34 institutions, females accounted for 26% of registrations. Nine
      institutions provided historical data, and these did not indicate that the sex
      difference is diminishing. Therefore, although efforts to ensure more equitable
      access to sports in the U.S. (i.e., Title IX) have produced many benefits,
      patterns of sports participation do not challenge the hypothesis of a large sex
      difference in interest and participation in physical competition.

PMID- 23155460
TI  - Identifying gender-preferred communication styles within online cancer
      communities: a retrospective, longitudinal analysis.
AB  - BACKGROUND: The goal of this research is to determine if different gender
      preferred social styles can be observed within the user interactions at an online
      cancer community. To achieve this goal, we identify and measure variables that
      pertain to each gender-specific social style. METHODS AND FINDINGS: We perform
      social network and statistical analysis on the communication flow of 8,388
      members at six different cancer forums over eight years. Kruskal-Wallis tests
      were conducted to measure the difference between the number of intimate (and
      highly intimate) dyads, relationship length, and number of communications. We
      determine that two patients are more likely to form an intimate bond on a gender
      specific cancer forum (ovarian P = <0.0001, breast P = 0.0089, prostate P =
      0.0021). Two female patients are more likely to form a highly intimate bond on a
      female-specific cancer forum (Ovarian P<0.0001, Breast P<0.01). Typically a male
      patient communicates with more members than a female patient (Ovarian forum P =
      0.0406, Breast forum P = 0.0013). A relationship between two patients is longer
      on the gender-specific cancer forums than a connection between two members not
      identified as patients (ovarian forum P = 0.00406, breast forum P = 0.00013,
      prostate forum P = .0.0003). CONCLUSION: The high level of interconnectedness
      among the prostate patients supports the hypothesis that men prefer to socialize
      in large, interconnected, less-intimate groups. A female patient is more likely
      to form a highly intimate connection with another female patient; this finding is
      consistent with the hypothesis that woman prefer fewer, more intimate
      connections. The relationships of same-gender cancer patients last longer than
      other relationships; this finding demonstrates homophily within these online
      communities. Our findings regarding online communication preferences are in
      agreement with research findings from person-to-person communication preference
      studies. These findings should be considered when designing online communities as
      well as designing and evaluating psychosocial and educational interventions for
      cancer patients.

PMID- 23155461
TI  - Mobile phones in a traffic flow: a geographical perspective to evening rush hour
      traffic analysis using call detail records.
AB  - Excessive land use and suburbanisation around densely populated urban areas has
      gone hand in hand with a growth in overall transportation and discussions about
      causality of traffic congestions. The objective of this paper is to gain new
      insight regarding the composition of traffic flows, and to reveal how and to what
      extent suburbanites' travelling affects rush hour traffic. We put forward an
      alternative methodological approach using call detail records of mobile phones to
      assess the composition of traffic flows during the evening rush hour in Tallinn,
      Estonia. We found that daily commuting and suburbanites influence transportation
      demand by amplifying the evening rush hour traffic, although daily commuting
      trips comprises only 31% of all movement at that time. The geography of the
      Friday evening rush hour is distinctive from other working days, presumably in
      connection with domestic tourism and leisure time activities. This suggests that
      the rise of the overall mobility of individuals due to societal changes may play
      a greater role in evening rush hour traffic conditions than does the impact of
      suburbanisation.

PMID- 23155462
TI  - Environmental enrichment reduces signs of boredom in caged mink.
AB  - Animals housed in impoverished cages are often labelled 'bored'. They have also
      been called 'apathetic' or 'depressed', particularly when profoundly inactive.
      However, these terms are rarely operationally defined and validated. As a
      negative state caused by under-stimulation, boredom should increase interest in
      stimuli of all kinds. Apathy (lack of interest), by contrast, should manifest as
      decreased interest in all stimuli, while anhedonia (loss of pleasure, a
      depressive symptom) should specifically decrease interest in normally rewarding
      stimuli. We tested the hypotheses that mink, a model carnivore, experience more
      boredom, depression-like apathy, or anhedonia in non-enriched (NE) cages than in
      complex, enriched (E) cages. We exposed 29 subjects (13 E, 16 NE) to ten stimuli
      categorized a priori as aversive (e.g. air puffs), rewarding (e.g. evoking
      chasing) or ambiguous/neutral (e.g. candles). Interest in stimuli was assessed
      via latencies to contact, contact durations, and durations oriented to stimuli.
      NE mink contacted all stimuli faster (P = 0.003) than E mink, and spent longer
      oriented to/in contact with them, albeit only significantly so for ambiguous ones
      (treatment*type P<0.013). With stimulus category removed from statistical models,
      interest in all stimuli was consistently higher among NE mink (P<0.0001 for all
      measures). NE mink also consumed more food rewards (P = 0.037). Finally, we
      investigated whether lying down while awake and stereotypic behaviour (both
      increased by NE housing) predicted these responses. Lying awake positively co
      varied with certain measures of increased exploration. In contrast, stereotypic
      'scrabbling' or locomotion (e.g. pacing) did not. Overall, NE mink showed no
      evidence of apathy or depression, but instead a heightened investigation of
      diverse stimuli consistent with boredom. This state was potentially indicated by
      spending much time lying still but awake (although this result requires
      replication). Boredom can thus be operationalized and assessed empirically in non
      human animals. It can also be reduced by environmental enrichment.

PMID- 23155463
TI  - PLK1 interacts and phosphorylates Axin that is essential for proper centrosome
      formation.
AB  - Abnormal amplification of centrosomes could lead to improper chromosome
      segregation and aneuploidy and is implicated in cancer development. Here, we
      demonstrate that Axin, a scaffolding protein in Wnt signaling, is phosphorylated
      by PLK1 during mitosis. Phosphorylation of Axin Ser-157 by PLK1 abolished Axin
      association with gamma-tubulin, while substitution of Ser-157 with alanine
      exhibited sustained interaction with gamma-tubulin. In addition, overexpression
      of Axin-S157A significantly increased the number of cells with multi-centrosomes.
      These results suggest that the phosphorylation status of Axin, mediated by PLK1,
      dynamically regulates its association with gamma-tubulin and centrosome formation
      and segregation.

PMID- 23155464
TI  - Demographic consequences of poison-related mortality in a threatened bird of
      prey.
AB  - Evidence for decline or threat of wild populations typically comes from multiple
      sources and methods that allow optimal integration of the available information,
      representing a major advance in planning management actions. We used integrated
      population modelling and perturbation analyses to assess the demographic
      consequences of the illegal use of poison for an insular population of Red Kites,
      Milvus milvus. We first pooled into a single statistical framework the annual
      census of breeding pairs, the available individual-based data, the average
      productivity and the number of birds admitted annually to the local
      rehabilitation centre. By combining these four types of information we were able
      to increase estimate precision and to obtain an estimate of the proportion of
      breeding adults, an important parameter that was not directly measured in the
      field and that is often difficult to assess. Subsequently, we used perturbation
      analyses to measure the expected change in the population growth rate due to a
      change in poison-related mortality. We found that poison accounted for 0.43 to
      0.76 of the total mortality, for yearlings and older birds, respectively. Results
      from the deterministic population model indicated that this mortality suppressed
      the population growth rate by 20%. Despite this, the population was estimated to
      increase, albeit slowly. This positive trend was likely maintained by a very high
      productivity (1.83 fledglings per breeding pair) possibly promoted by
      supplementary feeding, a situation which is likely to be common to many large
      obligate or facultative European scavengers. Under this hypothetical scenario of
      double societal costs (poisoning of a threatened species and feeding programs),
      increasing poison control would help to lower the public cost of maintaining
      supplementary feeding stations.

PMID- 23155465
TI  - Formalization, annotation and analysis of diverse drug and probe screening assay
      datasets using the BioAssay Ontology (BAO).
AB  - Huge amounts of high-throughput screening (HTS) data for probe and drug
      development projects are being generated in the pharmaceutical industry and more
      recently in the public sector. The resulting experimental datasets are
      increasingly being disseminated via publically accessible repositories. However,
      existing repositories lack sufficient metadata to describe the experiments and
      are often difficult to navigate by non-experts. The lack of standardized
      descriptions and semantics of biological assays and screening results hinder
      targeted data retrieval, integration, aggregation, and analyses across different
      HTS datasets, for example to infer mechanisms of action of small molecule
      perturbagens. To address these limitations, we created the BioAssay Ontology
      (BAO). BAO has been developed with a focus on data integration and analysis
      enabling the classification of assays and screening results by concepts that
      relate to format, assay design, technology, target, and endpoint. Previously, we
      reported on the higher-level design of BAO and on the semantic querying
      capabilities offered by the ontology-indexed triple store of HTS data. Here, we
      report on our detailed design, annotation pipeline, substantially enlarged
      annotation knowledgebase, and analysis results. We used BAO to annotate assays
      from the largest public HTS data repository, PubChem, and demonstrate its utility
      to categorize and analyze diverse HTS results from numerous experiments. BAO is
      publically available from the NCBO BioPortal at
      http://bioportal.bioontology.org/ontologies/1533. BAO provides controlled
      terminology and uniform scope to report probe and drug discovery screening assays
      and results. BAO leverages description logic to formalize the domain knowledge
      and facilitate the semantic integration with diverse other resources. As a
      consequence, BAO offers the potential to infer new knowledge from a corpus of
      assay results, for example molecular mechanisms of action of perturbagens.

PMID- 23155467
TI  - Probabilistic prediction of contacts in protein-ligand complexes.
AB  - We introduce a statistical method for evaluating atomic level 3D interaction
      patterns of protein-ligand contacts. Such patterns can be used for fast
      separation of likely ligand and ligand binding site combinations out of all those
      that are geometrically possible. The practical purpose of this probabilistic
      method is for molecular docking and scoring, as an essential part of a scoring
      function. Probabilities of interaction patterns are calculated conditional on
      structural x-ray data and predefined chemical classification of molecular
      fragment types. Spatial coordinates of atoms are modeled using a Bayesian
      statistical framework with parametric 3D probability densities. The parameters
      are given distributions a priori, which provides the possibility to update the
      densities of model parameters with new structural data and use the parameter
      estimates to create a contact hierarchy. The contact preferences can be defined
      for any spatial area around a specified type of fragment. We compared calculated
      contact point hierarchies with the number of contact atoms found near the contact
      point in a reference set of x-ray data, and found that these were in general in a
      close agreement. Additionally, using substrate binding site in cathechol-O
      methyltransferase and 27 small potential binder molecules, it was demonstrated
      that these probabilities together with auxiliary parameters separate well ligands
      from decoys (true positive rate 0.75, false positive rate 0). A particularly
      useful feature of the proposed Bayesian framework is that it also characterizes
      predictive uncertainty in terms of probabilities, which have an intuitive
      interpretation from the applied perspective.

PMID- 23155466
TI  - Islet-specific CTL cloned from a type 1 diabetes patient cause beta-cell
      destruction after engraftment into HLA-A2 transgenic NOD/scid/IL2RG null mice.
AB  - Despite increasing evidence that autoreactive CD8 T-cells are involved in both
      the initiation of type 1 diabetes (T1D) and the destruction of beta-cells, direct
      evidence for their destructive role in-vivo is lacking. To address a destructive
      role for autoreactive CD8 T-cells in human disease, we assessed the pathogenicity
      of a CD8 T-cell clone derived from a T1D donor and specific for an HLA-A2
      restricted epitope of islet-specific glucose-6-phosphatase catalytic-subunit
      related protein (IGRP). HLA-A2/IGRP tetramer staining revealed a higher frequency
      of IGRP-specific CD8 T-cells in the peripheral blood of recent onset human
      individuals than of healthy donors. IGRP(265-273)-specific CD8 T-cells that were
      cloned from the peripheral blood of a recent onset T1D individual were shown to
      secrete IFNgamma and Granzyme B after antigen-specific activation and lyse HLA-A2
      expressing murine islets in-vitro. Lytic capacity was also demonstrated in-vivo
      by specific killing of peptide-pulsed target cells. Using the HLA-A2 NOD-scid
      IL2rgamma(null) mouse model, HLA-A2-restricted IGRP-specific CD8 T-cells induced
      a destructive insulitis. Together, this is the first evidence that human HLA
      restricted autoreactive CD8 T-cells target HLA-expressing beta-cells in-vivo,
      demonstrating the translational value of humanized mice to study mechanisms of
      disease and therapeutic intervention strategies.

PMID- 23155468
TI  - Human breast cancer cells are redirected to mammary epithelial cells upon
      interaction with the regenerating mammary gland microenvironment in-vivo.
AB  - Breast cancer is the second leading cause of cancer deaths in the United States.
      At present, the etiology of breast cancer is unknown; however the possibility of
      a distinct cell of origin, i.e. a cancer stem cell, is a heavily investigated
      area of research. Influencing signals from the tissue niche are known to affect
      stem cells. Literature has shown that cancer cells lose their tumorigenic
      potential and display 'normal' behavior when placed into 'normal' ontogenic
      environments. Therefore, it may be the case that the tissue microenvironment is
      able to generate signals to redirect cancer cell fate. Previously, we showed that
      pluripotent human embryonal carcinoma cells could be redirected by the
      regenerating mammary gland microenvironment to contribute epithelial progeny for
      'normal' gland development in-vivo. Here, we show that that human metastatic, non
      metastatic, and metastasis-suppressed breast cancer cells proliferate and
      contribute to normal mammary gland development in-vivo without tumor formation.
      Immunochemistry for human-specific mitochondria, keratin 8 and 14, as well as
      human-specific milk proteins (alpha-lactalbumin, impregnated transplant hosts)
      confirmed the presence of human cell progeny. Features consistent with normal
      mammary gland development as seen in intact hosts (duct, lumen formation,
      development of secretory acini) were recapitulated in both primary and secondary
      outgrowths from chimeric implants. These results suggest the dominance of the
      tissue microenvironment over cancer cell fate. This work demonstrates that
      cultured human breast cancer cells (metastatic and non-metastatic) respond
      developmentally to signals generated by the mouse mammary gland microenvironment
      during gland regeneration in-vivo.

PMID- 23155469
TI  - Sotos syndrome is associated with deregulation of the MAPK/ERK-signaling pathway.
AB  - Sotos syndrome (SoS) is characterized by tall stature, characteristic
      craniofacial features and mental retardation. It is caused by haploinsufficiency
      of the NSD1 gene. In this study, our objective was to identify downstream
      effectors of NSD1 and to map these effectors in signaling pathways associated
      with growth. Genome-wide expression studies were performed on dermal fibroblasts
      from SoS patients with a confirmed NSD1 abnormality. To substantiate those
      results, phosphorylation, siRNA and transfection experiments were performed. A
      significant association was demonstrated with the Mitogen-Activated Protein
      Kinase (MAPK) pathway. Members of the fibroblast growth factor family such as
      FGF4 and FGF13 contributed strongly to the differential expression in this
      pathway. In addition, a diminished activity state of the MAPK/ERK pathway was
      demonstrated in SoS. The Ras Interacting Protein 1 (RASIP1) was identified to
      exhibit upregulated expression in SoS. It was shown that RASIP1 dose-dependently
      potentiated bFGF induced expression of the MAPK responsive SBE reporter providing
      further support for a link between NSD1 and the MAPK/ERK signaling pathway.
      Additionally, we demonstrated NSD1 expression in the terminally differentiated
      hypertrophic chondrocytes of normal human epiphyseal growth plates. In short
      stature syndromes such as hypochondroplasia and Noonan syndrome, the activation
      level of the FGF-MAPK/ERK-pathway in epiphyseal growth plates is a determining
      factor for statural growth. In analogy, we propose that deregulation of the
      MAPK/ERK pathway in SoS results in altered hypertrophic differentiation of NSD1
      expressing chondrocytes and may be a determining factor in statural overgrowth
      and accelerated skeletal maturation in SoS.

PMID- 23155470
TI  - Quiescent fibroblasts are more active in mounting robust inflammatory responses
      than proliferative fibroblasts.
AB  - Quiescent cells are considered to be dormant. However, recent studies suggest
      that quiescent fibroblasts possess active metabolic profile and certain
      functional characteristics. We previously observed that serum-starved quiescent
      fibroblasts respond to proinflammatory stimuli by robust expression of
      cyclooxygenase-2 (COX-2), which declines after the quiescent fibroblasts are
      driven to proliferation. In this study, we elucidated the underlying signaling
      and transcriptional mechanism and identified by microarray genes with similar
      differential expression. By using pharmacological inhibitors coupled with gene
      silencing, we uncovered the key role of protein kinase C delta (PKCdelta) and
      extracellular signal regulated protein kinase 1/2 (ERK1/2) signaling in mediating
      COX-2 expression in quiescent cells. Surprisingly, COX-2 expression in
      proliferative cells was not blocked by PKCdelta or ERK1/2 inhibitors due to
      intrinsic inhibition of PKCdelta and ERK1/2 in proliferative cells. Restrained
      COX-2 transcription in proliferative cells was attributable to reduced NF-kappaB
      binding. Microarray analysis identified 35 genes whose expressions were more
      robust in quiescent than in proliferative cells. A majority of those genes belong
      to proinflammatory cytokines, chemokines, adhesive molecules and
      metalloproteinases, which require NF-kappaB for transcription. Quiescent
      fibroblasts had a higher migratory activity than proliferative fibroblasts as
      determined by the transwell assay. Selective COX-2 inhibition reduced migration
      which was restored by prostaglandin E(2). As COX-2 and inflammatory mediators
      induce DNA oxidation, we measured 8-hydroxydeoxyguanosine (8-OHdG) in quiescent
      vs. proliferative fibroblasts. PMA-induced 8-OHdG accumulation was significantly
      higher in quiescent than in proliferative fibroblasts. These findings indicate
      that quiescent fibroblasts (and probably other quiescent cells) are at the
      forefront in mounting inflammatory responses through expression of an array of
      proinflammatory genes via the PKCdelta/ERK1/2 signaling pathway.

PMID- 23155471
TI  - Acute ethanol exposure increases the susceptibility of the donor hearts to
      ischemia/reperfusion injury after transplantation in rats.
AB  - BACKGROUND: Many donor organs come from youths involved in alcohol-related
      accidental death. The use of cardiac allografts for transplantation from donors
      after acute poisoning is still under discussion while acute ethanol intoxication
      is associated with myocardial functional and morphological changes. The aims of
      this work were 1) to evaluate in rats the time-course cardiac effects of acute
      ethanol-exposure and 2) to explore how its abuse by donors might affect
      recipients in cardiac pump function after transplantation. METHODS: Rats received
      saline or ethanol (3.45 g/kg, ip). We evaluated both the mechanical and
      electrical aspects of cardiac function 1 h, 6 h or 24 h after injection. Plasma
      cardiac troponin-T and glucose-levels were measured and histological examination
      of the myocardium was performed. In addition, heart transplantation was
      performed, in which donors received ethanol 6 h or 24 h prior to explantation.
      Graft function was measured 1 h or 24 h after transplantation. Myocardial TBARS
      concentration was measured; mRNA and protein expression was assessed by
      quantitative real-time PCR and Western blot, respectively. RESULTS: Ethanol
      administration resulted in decreased load-dependent (-34 +/- 9%) and load
      independent (-33 +/- 12%) contractility parameters, LV end-diastolic pressure and
      elevated blood glucose levels at 1 h, which were reversed to the level of
      controls after 6 h and 24 h. In contrast to systolic dysfunction, active
      relaxation and passive stiffness are slowly recovered or sustained during 24 h.
      Moreover, troponin-T-levels were increased at 1 h, 6 h and 24 h after ethanol
      injection. ST-segment elevation (+47 +/- 10%), elongated QT-interval (+38 +/-
      4%), enlarged cardiomyocyte, DNA-strand breaks, increased both mRNA and protein
      levels of superoxide dismutase-1, glutathione peroxydase-4, cytochrome-c-oxidase
      and metalloproteinase-9 were observed 24 h following ethanol-exposure. After
      heart transplantation, decreased myocardial contractility and relaxation,
      oxidative stress and altered protein expression were observed. CONCLUSIONS: These
      results demonstrate acute alcohol abuse increases the susceptibility of donor
      hearts to ischemia/reperfusion in a rat heart transplant model even though the
      global contractile function recovers 6 h after ethanol-administration.

PMID- 23155472
TI  - Transcriptome profiling analysis reveals that flavonoid and ascorbate-glutathione
      cycle are important during anther development in Upland cotton.
AB  - BACKGROUND: Previous transcriptome profiling studies have investigated the
      molecular mechanisms of pollen and anther development, and identified many genes
      involved in these processes. However, only 51 anther ESTs of Upland cotton
      (Gossypium hirsutum) were found in NCBI and there have been no reports of
      transcriptome profiling analyzing anther development in Upland cotton, a major
      fiber crop in the word. METHODOLOGY/PRINCIPAL FINDING: Ninety-eight hundred and
      ninety-six high quality ESTs were sequenced from their 3'-ends and assembled into
      6,643 unigenes from a normalized, full-length anther cDNA library of Upland
      cotton. Combined with previous sequenced anther-related ESTs, 12,244 unigenes
      were generated as the reference genes for digital gene expression (DGE) analysis.
      The DGE was conducted on anthers that were isolated at tetrad pollen (TTP),
      uninucleate pollen (UNP), binucleate pollen (BNP) and mature pollen (MTP) periods
      along with four other tissues, i.e., roots (RO), stems (ST), leaves (LV) and
      embryos (EB). Through transcriptome profiling analysis, we identified 1,165 genes
      that were enriched at certain anther development periods, and many of them were
      involved in starch and sucrose metabolism, pentose and glucuronate
      interconversion, flavonoid biosynthesis, and ascorbate and aldarate metabolism.
      CONCLUSIONS/SIGNIFICANCE: We first generated a normalized, full-length cDNA
      library from anthers and performed transcriptome profiling analysis of anther
      development in Upland cotton. From these results, 10,178 anther expressed genes
      were identified, among which 1,165 genes were stage-enriched in anthers. And many
      of these stage-enriched genes were involved in some important processes
      regulating anther development.

PMID- 23155473
TI  - Linking personality to larval energy reserves in rainbow trout (Oncorhynchus
      mykiss).
AB  - There is a surging interest in the evolution, ecology and physiology of
      personality differences. However, most of the studies in this research area have
      been performed in adult animals. Trait variations expressed early in development
      and how they are related to the ontogeny of an animal's personality are far less
      studied. Genetic differences as well as environmental factors causing functional
      variability of the central serotonergic system have been related to personality
      differences in vertebrates, including humans. Such gene-environment interplay
      suggests that the central serotonergic system plays an important role in the
      ontogeny of personality traits. In salmonid fishes, the timing of emergence from
      spawning nests is related to energy reserves, aggression, and social dominance.
      However, it is currently unknown how the size of the yolk reserve is reflected on
      aggression and dominance, or if these traits are linked to differences in
      serotonergic transmission in newly emerged larvae. In this study we investigated
      the relationship between yolk reserves, social dominance, and serotonergic
      transmission in newly emerged rainbow trout (Oncorhynchus mykiss) larvae. This
      was conducted by allowing larvae with the same emergence time, but with different
      yolk sizes, to interact in pairs for 24 h. The results show that individuals with
      larger yolks performed more aggressive acts, resulting in a suppression of
      aggression in individuals with smaller yolks. A higher brain serotonergic
      activity confirmed subordination in larvae with small yolks. The relationship
      between social dominance and yolk size was present in siblings, demonstrating a
      link between interfamily variation in energy reserves and aggression, and
      suggests that larger yolk reserves fuel a more aggressive personality during the
      initial territorial establishment in salmonid fishes. Furthermore, socially naive
      larvae with big yolks had lower serotonin levels, suggesting that other factors
      than the social environment causes variation in serotonergic transmission,
      underlying individual variation in aggressive behavior.

PMID- 23155474
TI  - Toward the beginning of time: circadian rhythms in metabolism precede rhythms in
      clock gene expression in mouse embryonic stem cells.
AB  - The appearance, progression, and potential role for circadian rhythms during
      early development have previously focused mainly on the suprachiasmatic nucleus
      (SCN) and peri- and postnatal expression of canonical clock genes. More recently,
      gene expression studies in embryonic stem cells have shown that some clock genes
      are expressed in undifferentiated cells; however rhythmicity was only established
      when cells are directed toward a neural fate. These studies also concluded that a
      functional clock is not present in ESCs, based solely on their gene expression.
      The null hypothesis underlying the present study is that embryonic stem cells
      become rhythmic in both clock gene expression and glucose utilization only when
      allowed to spontaneously differentiate. Undifferentiated stem cells (ESCs, n = 6
      cultures/timepoint for all experiments) were either maintained in their
      pluripotent state or released into differentiation (dESCs, n = 6
      cultures/timepoint for all experiments). Glucose utilization was assayed through
      2-deoxyglucose uptake measurement, and clock gene and glucose transporter
      expression was assayed every 4 hours for 2 days in ESCs and dESCs by quantitative
      PCR (qPCR) in the same cell lysates. Undifferentiated stem cells expressed a self
      sustained rhythm in glucose uptake that was not coincident with rhythmic
      expression of clock genes. This physiological rhythm was paralleled by glucose
      transporter mRNA expression. Upon differentiation, circadian patterns of some but
      not all clock genes were expressed, and the amplitude of the glucose utilization
      rhythm was enhanced in dESCs. These data provide the earliest evidence of a
      functional circadian clock, in addition to further challenging the idea that
      rhythmic transcription of clock genes are necessary for rhythmic physiological
      output and suggest a role for a clock-controlled physiology in the earliest
      stages of development.

PMID- 23155475
TI  - Neutrophil elastase alters the murine gut microbiota resulting in enhanced
      Salmonella colonization.
AB  - The intestinal microbiota has been found to play a central role in the
      colonization of Salmonella enterica serovar Typhimurium in the gastrointestinal
      tract. In this study, we present a novel process through which Salmonella benefit
      from inflammatory induced changes in the microbiota in order to facilitate
      disease. We show that Salmonella infection in mice causes recruitment of
      neutrophils to the gut lumen, resulting in significant changes in the composition
      of the intestinal microbiota. This occurs through the production of the enzyme
      elastase by neutrophils. Administration of recombinant neutrophil elastase to
      infected animals under conditions that do not elicit neutrophil recruitment
      caused shifts in microbiota composition that favored Salmonella colonization,
      while inhibition of neutrophil elastase reduced colonization. This study reveals
      a new relationship between the microbiota and the host during infection.

PMID- 23155477
TI  - LETTER TO THE EDITOR Correction of Tethered Tracheostomy Scar Using Dermofat
      Graft.

PMID- 23155478
TI  - Transmission of Ebola virus from pigs to non-human primates.
AB  - Ebola viruses (EBOV) cause often fatal hemorrhagic fever in several species of
      simian primates including human. While fruit bats are considered natural
      reservoir, involvement of other species in EBOV transmission is unclear. In 2009,
      Reston-EBOV was the first EBOV detected in swine with indicated transmission to
      humans. In-contact transmission of Zaire-EBOV (ZEBOV) between pigs was
      demonstrated experimentally. Here we show ZEBOV transmission from pigs to
      cynomolgus macaques without direct contact. Interestingly, transmission between
      macaques in similar housing conditions was never observed. Piglets inoculated oro
      nasally with ZEBOV were transferred to the room housing macaques in an open
      inaccessible cage system. All macaques became infected. Infectious virus was
      detected in oro-nasal swabs of piglets, and in blood, swabs, and tissues of
      macaques. This is the first report of experimental interspecies virus
      transmission, with the macaques also used as a human surrogate. Our finding may
      influence prevention and control measures during EBOV outbreaks.

PMID- 23155476
TI  - Expression profile in rice panicle: insights into heat response mechanism at
      reproductive stage.
AB  - Rice at reproductive stage is more sensitive to environmental changes, and little
      is known about the mechanism of heat response in rice panicle. Here, using rice
      microarray, we provided a time course gene expression profile of rice panicle at
      anther developmental stage 8 after 40 degrees C treatment for 0 min, 20 min, 60
      min, 2 h, 4 h, and 8 h. The identified differentially expressed genes were mainly
      involved in transcriptional regulation, transport, cellular homeostasis, and
      stress response. The predominant transcription factor gene families responsive to
      heat stress were Hsf, NAC, AP2/ERF, WRKY, MYB, and C(2)H(2). KMC analysis
      discovered the time-dependent gene expression pattern under heat stress. The
      motif co-occurrence analysis on the promoters of genes from an early up-regulated
      cluster showed the important roles of GCC box, HSE, ABRE, and CE3 in response to
      heat stress. The regulation model central to ROS combined with transcriptome and
      ROS quantification data in rice panicle indicated the great importance to
      maintain ROS balance and the existence of wide cross-talk in heat response. The
      present study increased our understanding of the heat response in rice panicle
      and provided good candidate genes for crop improvement.

PMID- 23155479
TI  - Neural correlates of lyrical improvisation: an FMRI study of freestyle rap.
AB  - The neural correlates of creativity are poorly understood. Freestyle rap provides
      a unique opportunity to study spontaneous lyrical improvisation, a
      multidimensional form of creativity at the interface of music and language. Here
      we use functional magnetic resonance imaging to characterize this process. Task
      contrast analyses indicate that improvised performance is characterized by
      dissociated activity in medial and dorsolateral prefrontal cortices, providing a
      context in which stimulus-independent behaviors may unfold in the absence of
      conscious monitoring and volitional control. Connectivity analyses reveal
      widespread improvisation-related correlations between medial prefrontal,
      cingulate motor, perisylvian cortices and amygdala, suggesting the emergence of a
      network linking motivation, language, affect and movement. Lyrical improvisation
      appears to be characterized by altered relationships between regions coupling
      intention and action, in which conventional executive control may be bypassed and
      motor control directed by cingulate motor mechanisms. These functional
      reorganizations may facilitate the initial improvisatory phase of creative
      behavior.

PMID- 23155480
TI  - Development of miniaturized walking biological machines.
AB  - The quest to 'forward-engineer' and fabricate biological machines remains a grand
      challenge. Towards this end, we have fabricated locomotive "bio-bots" from
      hydrogels and cardiomyocytes using a 3D printer. The multi-material bio-bot
      consisted of a 'biological bimorph' cantilever structure as the actuator to power
      the bio-bot, and a base structure to define the asymmetric shape for locomotion.
      The cantilever structure was seeded with a sheet of contractile cardiomyocytes.
      We evaluated the locomotive mechanisms of several designs of bio-bots by changing
      the cantilever thickness. The bio-bot that demonstrated the most efficient
      mechanism of locomotion maximized the use of contractile forces for overcoming
      friction of the supporting leg, while preventing backward movement of the
      actuating leg upon relaxation. The maximum recorded velocity of the bio-bot was
      ~236 um s(-1), with an average displacement per power stroke of ~354 um and
      average beating frequency of ~1.5 Hz.

PMID- 23155481
TI  - New thermodynamical force in plasma phase space that controls turbulence and
      turbulent transport.
AB  - Physics of turbulence and turbulent transport has been developed on the central
      dogma that spatial gradients constitute the controlling parameters, such as
      Reynolds number and Rayleigh number. Recent experiments with the nonequilibrium
      plasmas in magnetic confinement devices, however, have shown that the turbulence
      and transport change much faster than global parameters, after an abrupt change
      of heating power. Here we propose a theory of turbulence in inhomogeneous
      magnetized plasmas, showing that the heating power directly influences the
      turbulence. New mechanism, that an external source couples with plasma
      fluctuations in phase space so as to affect turbulence, is investigated. A new
      thermodynamical force in phase-space, i.e., the derivative of heating power by
      plasma pressure, plays the role of new control parameter, in addition to spatial
      gradients. Following the change of turbulence, turbulent transport is modified
      accordingly. The condition under which this new effect can be observed is also
      evaluated.

PMID- 23155482
TI  - Initial geometries, interaction mechanism and high stability of silicene on
      Ag(111) surface.
AB  - Using ab initio methods, we have investigated the structures and stabilities of
      Si(N) clusters (N <= 24) on Ag(111) surface as the initial stage of silicene
      growth. Unlike the dome-shaped graphene clusters, Si clusters prefer nearly flat
      structures with low buckling, more stable than directly deposition of the 3D
      freestanding Si clusters on Ag surface. The p-d hybridization between Ag and Si
      is revealed as well as sp(2) characteristics in Si(N)@Ag(111). Three types of
      silicene superstructures on Ag(111) surface have been considered and the
      simulated STM images are compared with experimental observations. Molecular
      dynamic simulations show high thermal stability of silicene on Ag(111) surfaces,
      contrast to that on Rh(111). The present theoretical results constitute a
      comprehensive picture about the interaction mechanism of silicene on Ag(111)
      surface and explain the superiority of Ag substrate for silicene growth, which
      would be helpful for improving the experimentally epitaxial growth of silicene.

PMID- 23155483
TI  - Correlative light and electron microscopy using cathodoluminescence from
      nanoparticles with distinguishable colours.
AB  - Correlative light and electron microscopy promises to combine molecular
      specificity with nanoscale imaging resolution. However, there are substantial
      technical challenges including reliable co-registration of optical and electron
      images, and rapid optical signal degradation under electron beam irradiation.
      Here, we introduce a new approach to solve these problems: imaging of stable
      optical cathodoluminescence emitted in a scanning electron microscope by
      nanoparticles with controllable surface chemistry. We demonstrate well-correlated
      cathodoluminescence and secondary electron images using three species of
      semiconductor nanoparticles that contain defects providing stable, spectrally
      distinguishable cathodoluminescence. We also demonstrate reliable surface
      functionalization of the particles. The results pave the way for the use of such
      nanoparticles for targeted labeling of surfaces to provide nanoscale mapping of
      molecular composition, indicated by cathodoluminescence colour, simultaneously
      acquired with structural electron images in a single instrument.

PMID- 23155484
TI  - Ribosomal frameshifting used in influenza A virus expression occurs within the
      sequence UCC_UUU_CGU and is in the +1 direction.
AB  - Programmed ribosomal frameshifting is used in the expression of many virus genes
      and some cellular genes. In eukaryotic systems, the most well-characterized
      mechanism involves -1 tandem tRNA slippage on an X_XXY_YYZ motif. By contrast,
      the mechanisms involved in programmed +1 (or -2) slippage are more varied and
      often poorly characterized. Recently, a novel gene, PA-X, was discovered in
      influenza A virus and found to be expressed via a shift to the +1 reading frame.
      Here, we identify, by mass spectrometric analysis, both the site (UCC_UUU_CGU)
      and direction (+1) of the frameshifting that is involved in PA-X expression.
      Related sites are identified in other virus genes that have previously been
      proposed to be expressed via +1 frameshifting. As these viruses infect insects
      (chronic bee paralysis virus), plants (fijiviruses and amalgamaviruses) and
      vertebrates (influenza A virus), such motifs may form a new class of +1
      frameshift-inducing sequences that are active in diverse eukaryotes.

PMID- 23155485
TI  - A Type III restriction-modification system in Mycoplasma mycoides subsp. capri.
AB  - The sequenced genome of Mycoplasma mycoides subsp. capri revealed the presence of
      a Type III restriction-modification system (MmyCI). The methyltransferase
      (modification) subunit of MmyCI (M.MmyCI) was shown to recognize the sequence 5'
      TGAG-3' and methylate the adenine. The coding region of the methyltransferase
      gene contains 12 consecutive AG dinucleotide repeats that result in a
      translational termination at a TAA codon immediately beyond the repeat region.
      This strain does not have MmyCI activity. A clone was found with 10 AG repeats
      such that the gene is in frame, and this strain has MmyCI activity, suggesting
      that the expression of the MmyCI methyltransferase may be phase variable.

PMID- 23155486
TI  - Mechanistic and structural basis for inhibition of thymidylate synthase ThyX.
AB  - Nature has established two mechanistically and structurally unrelated families of
      thymidylate synthases that produce de novo thymidylate or dTMP, an essential DNA
      precursor. Representatives of the alternative flavin-dependent thymidylate
      synthase family, ThyX, are found in a large number of microbial genomes, but are
      absent in humans. We have exploited the nucleotide binding pocket of ThyX
      proteins to identify non-substrate-based tight-binding ThyX inhibitors that
      inhibited growth of genetically modified Escherichia coli cells dependent on thyX
      in a manner mimicking a genetic knockout of thymidylate synthase. We also solved
      the crystal structure of a viral ThyX bound to 2-hydroxy-3-(4-methoxybenzyl)-1,4
      naphthoquinone at a resolution of 2.6 A. This inhibitor was found to bind within
      the conserved active site of the tetrameric ThyX enzyme, at the interface of two
      monomers, partially overlapping with the dUMP binding pocket. Our studies provide
      new chemical tools for investigating the ThyX reaction mechanism and establish a
      novel mechanistic and structural basis for inhibition of thymidylate synthesis.
      As essential ThyX proteins are found e.g. in Mycobacterium tuberculosis and
      Helicobacter pylori, our studies have also potential to pave the way towards the
      development of new anti-microbial compounds.

PMID- 23155488
TI  - Exposure of patients to ionizing radiation. What are the risks?

PMID- 23155487
TI  - Manipulation of PK-M mutually exclusive alternative splicing by antisense
      oligonucleotides.
AB  - Alternative splicing of the pyruvate kinase M gene involves a choice between
      mutually exclusive exons 9 and 10. Use of exon 10 to generate the M2 isoform is
      crucial for aerobic glycolysis (the Warburg effect) and tumour growth. We
      previously demonstrated that splicing enhancer elements that activate exon 10 are
      mainly found in exon 10 itself, and deleting or mutating these elements increases
      the inclusion of exon 9 in cancer cells. To systematically search for new
      enhancer elements in exon 10 and develop an effective pharmacological method to
      force a switch from PK-M2 to PK-M1, we carried out an antisense oligonucleotide
      (ASO) screen. We found potent ASOs that target a novel enhancer in exon 10 and
      strongly switch the splicing of endogenous PK-M transcripts to include exon 9. We
      further show that the ASO-mediated switch in alternative splicing leads to
      apoptosis in glioblastoma cell lines, and this is caused by the downregulation of
      PK-M2, and not by the upregulation of PK-M1. These data highlight the potential
      of ASO-mediated inhibition of PK-M2 splicing as therapy for cancer.

PMID- 23155489
TI  - Assessing physical activity and related correlates among adults in Hawai'i.
AB  - Regular physical activity has been shown to reduce the risk of cardiovascular
      disease, stroke, some mental illnesses and some cancer. Despite the well-known
      benefits of physical activity, about half of the adults in the United States and
      Hawai'i do not get enough. Rates of physical activity differ greatly among ethnic
      groups and interventions to increase physical activity may need to be tailored
      for specific ethnicities. In this study, 3,588 adults living in Hawai'i completed
      a random digit dial survey on their physical activity level. Native Hawaiians and
      Whites were more likely to be active than Chinese, Filipino and Japanese
      respondents. Multivariate logistic regressions analyses eliminated differences
      between Whites, Filipinos and Chinese respondents; however, Native Hawaiians were
      still more likely to report meeting physical activity guidelines and Japanese
      were less likely. Other significant predictors included being younger, male,
      having a job involving heavy labor, being in the normal weight range, being in
      good or excellent health, having high self-efficacy, spending less time sitting,
      and walking a dog more frequently. Differences in meeting physical activity
      guidelines can be used in planning future public health campaigns.

PMID- 23155490
TI  - Door-to-balloon time in acute ST segment elevation myocardial infarction--further
      experience.
AB  - Early coronary reperfusion has been established as the optimal treatment for
      acute ST segment elevation myocardial infarction. A treatment protocol,
      previously described, has been designed to reduce delay in achieving
      recanalization of the culprit coronary artery. Over a period of about 4 years,
      Door-to-Balloon time has been analyzed for patients arriving in the Emergency
      Department with this condition. During that time the process was enhanced by the
      ability of ambulance personnel to transmit 12 lead EKG's from the field. Door-to
      Balloon times have been analyzed and compared to the American College of
      Cardiology target of 90 minutes. After just over one year of gradually improving
      results, 100% compliance was achieved. From that time on, this was achieved
      during the period under consideration in 97% of cases.

PMID- 23155491
TI  - Inflammatory bowel disease treatment and non-melanoma skin cancer: a case report.
AB  - Immunosuppressant medications for Inflammatory Bowel Disease can help with both
      symptoms and disease progression. However, like immunosuppressants used in
      transplant patients, they are now suspect of contributing to nonmelenoma skin
      cancer (NMSC). Presented is a case of a 57-year-old Jewish man with Crohn's
      Disease who was diagnosed with a total of 84 NMSCs. We hope to elucidate the risk
      of immunosuppressants, particularly the thiopurines, on the development of NMSC.

PMID- 23155493
TI  - Medical school hotline: the Department of Native Hawaiian Health at the John A.
      Burns School of Medicine.

PMID- 23155495
TI  - Pilidiella tibouchinae sp. nov. associated with foliage blight of Tibouchina
      granulosa (quaresmeira) in Brazil.
AB  - Tibouchina granulosa (Melastomataceae), Brazilian glorytree (Brazilian common
      name - quaresmeira), a common tree of the Atlantic Forest of Brazil, is widely
      used as an ornamental for its violet or pink blossoms. Little is known about
      fungal diseases affecting this species, although these represent a known
      limitation for its cultivation in nurseries. Among these there is a foliage
      blight that occurs in combination with distortion of branch apices and die-back.
      A consistent association of a species of Pilidiella with the diseased tissues was
      observed. The fungus was isolated in pure culture and based on its morphology and
      DNA phylogeny, we conclude that it represents a new species, for which the name
      Pilidiella tibouchinae is introduced.

PMID- 23155496
TI  - Reappraisal and neotypification of Phyllachora feijoae.
AB  - Acca sellowiana (Myrtaceae), feijoa (in Brazil, goiaba da serra), is a native
      southern South America tree that produces edible fruits which, although only
      occasionally cultivated in South America, became a significant fruit crop in New
      Zealand. Recently, during surveys for fungal pathogens of feijoa in southern
      Brazil, several plants were found bearing tar-spot symptoms caused by a species
      of Phyllachora. A literature search enabled us to identify the fungus as
      Phyllachora feijoae, a little-known species originally described in the 19(th)
      century by H. Rehm and later transferred to the genus Catacauma. The name
      Catacauma feijoae, although now regarded as a later synonym of P. feijoae is
      still mistakenly in use (as, for instance, in the Brazilian list of fungi on
      plants). The type specimen was most probably deposited in the Botanisches Garten
      und Museum Berlin-Dahlem (B) and lost or destroyed during World War II, and could
      not be located. The recent recollection of abundant material of this fungus in
      the vicinity of Pelotas (Rio Grande do Sul, Brazil) allowed its re-examination
      and neotypification. Phyllachora feijoae is also illustrated here for the first
      time.

PMID- 23155497
TI  - Managing and coping with names of pleomorphic fungi in a period of transition.
AB  - An explanation is provided of the recent changes in the International Code of
      Nomenclature for algae, fungi and plants relating to the ending of the separate
      naming of different states of fungi with a pleomorphic life-cycle. Issues
      relating to their implementation are discussed, including problems of defining
      "widely used", author citations, proofs of holomorphy, typification, the
      preparation of "Lists of accepted and rejected names" (with a possible
      timetable), relationship to the existing processes of sanctioning and
      conservation or rejection, and steps to be considered for the future. This
      material is presented here to stimulate debate on the actions that should be
      taken by individuals, and responsible committees, in the current period of
      transition to a system of fungal nomenclature fit for the 21(st) century.

PMID- 23155498
TI  - Afrocantharellus gen. stat. nov. is part of a rich diversity of African
      Cantharellaceae.
AB  - A new genus in the Cantharellaceae, Afrocantharellus, is recognized based on
      results from phylogenetic analyses of rDNA LSU and concatenated LSU/5.8-ITS2/ATP6
      data. It was previously recognized as a subgenus, but comprehensive fieldwork and
      the acquisition of numerous sequences for previously neglected African
      Cantharellus species formed the basis for a reappraisal of generic and species
      delimitations. Afrocantharellus is characterized morphologically by the
      basidiomes having thick, distantly spaced diverging folds of variegated colour.
      In contrast to most of Cantharellus, Afrocantharellus mostly lacks clamp
      connections. Phylogenies of Cantharellus and Afrocantharellus based on LSU and a
      concatenated data set are provided, along with descriptions of and a key to the
      four species and one form of Afrocantharellus recognized. Six new combinations
      are made.

PMID- 23155499
TI  - The identity of Cintractia disciformis: reclassification and synonymy of a
      southern Asian smut parasitic on Carex sect. Aulocystis.
AB  - The identity of a neglected smut fungus, Cintractia disciformis, described from
      Carex hirtella in the Western Himalaya, India is reassessed. The species is
      excluded from Cintractia and is confirmed as a distinct species of Anthracoidea.
      Two smuts, A. nepalensis on Carex nakaoana in Nepal, and A. haematostomae on
      Carex haematostoma in China, are similar morphologically and considered to be
      later heterotypic synonyms of Cintractia disciformis. The appropriate
      nomenclatural combination for this species, Anthracoidea disciformis comb. nov.,
      is validated.

PMID- 23155500
TI  - Ceratocystis eucalypticola sp. nov. from Eucalyptus in South Africa and
      comparison to global isolates from this tree.
AB  - Eucalyptus trees, mostly native to Australia, are widely planted in the tropics
      and Southern Hemisphere for the production of wood and pulp. Worldwide surveys of
      diseases on these trees have yielded a large collection of Ceratocystis isolates
      from dying trees or from wounds on their stems. The aim of this study was to
      characterise these isolates and to consider their relatedness to each other.
      Culture appearance, morphological features and a distinctive fruity odour in all
      cultures were typical of species in the Ceratocystis fimbriatasensu lato (s.
      lat.) complex. Phylogenetic analyses of sequences for the combined ITS, betat-1
      and TEF1-alpha gene regions revealed a genetically diverse group of isolates
      residing in a single large clade, that were distinct from all other species in
      the C. fimbriatas. lat. complex. Based on morphology and phylogenetic inference,
      the Eucalyptus isolates are recognised as closely related. The South African
      isolates are described here as a new species, C. eucalypticola.

PMID- 23155501
TI  - Aspergillus section Versicolores: nine new species and multilocus DNA sequence
      based phylogeny.
AB  - beta-tubulin, calmodulin, internal transcribed spacer and partial lsu-rDNA, RNA
      polymerase 2, DNA replication licensing factor Mcm7, and pre-rRNA processing
      protein Tsr1 were amplified and sequenced from numerous isolates belonging to
      Aspergillus sect. versicolor. The isolates were analyzed phylogenetically using
      the concordance model to establish species boundaries. Aspergillus
      austroafricanus, A. creber, A. cvjetkovicii, A. fructus, A. jensenii, A.
      puulaauensis, A. subversicolor, A. tennesseensis and A. venenatus are described
      as new species and A. amoenus, A. protuberus,A. sydowii, A. tabacinus and A.
      versicolor are accepted as distinct species on the basis of molecular and
      phenotypic differences. PCR primer pairs used to detect A. versicolor in sick
      building syndrome studies have a positive reaction for all of the newly described
      species except A. subversicolor.

PMID- 23155502
TI  - The impacts of the discontinuation of dual nomenclature of pleomorphic fungi: the
      trivial facts, problems, and strategies.
AB  - The symposium "One fungus = Which name" held in Amsterdam 12-13 April 2012,
      addressed the drastic changes in the naming of pleomorphic fungi adopted by the
      18(th) International Botanical Congress in Melbourne in 2011. Possible solutions
      and ways to face resulting problems were suggested. The fundamental change is
      that under the new rules fungi in future will be treated nomenclaturally like
      plants and all other groups of organisms ruled by the ICN, i.e. with one correct
      name for each species. Numerous discussions and statements during the Symposium
      reflected widespread anxieties that these rules could negatively influence
      taxonomic work on pleomorphic fungi. However, they are groundless, being based on
      misunderstandings and confusion of nomenclature and taxonomy. With pleomorphic
      fungi, taxonomists will in future have to answer the question whether different
      morphs can represent one fungus (taxon), but this remains a taxonomic decision
      and has nothing to do with nomenclature. Furthermore, the ICN does not and cannot
      rule on how this decision is made. Thus it cannot provide rules based solely on
      methods involving morphology in vivo or in vitro, molecular analyses,
      physiological and biochemical data, inoculation experiments in pathogenic groups
      or any other methods or combinations of them. It is up to the taxonomist to
      select appropriate methods and to decide which data are sufficient to introduce
      new taxa. Some future problems and strategies around the application of anamorph-
      and teleomoph-typified taxon names (genera and species), are discussed here,
      using the recently monographed powdery mildews (Erysiphales) as an example.

PMID- 23155503
TI  - The importance of fungi and of mycology for a global development of the
      bioeconomy.
AB  - The vision of the European common research programme for 2014-2020, called
      Horizon 2020, is to create a smarter, more sustainable and more inclusive
      society. However, this is a global endeavor, which is important for mycologists
      all over the world because it includes a special role for fungi and fungal
      products. After ten years of research on industrial scale conversion of biowaste,
      the conclusion is that the most efficient and gentle way of converting
      recalcitrant lignocellulosic materials into high value products for industrial
      purposes, is through the use of fungal enzymes. Moreover, fungi and fungal
      products are also instrumental in producing fermented foods, to give storage
      stability and improved health. Climate change will lead to increasingly severe
      stress on agricultural production and productivity, and here the solution may
      very well be that fungi will be brought into use as a new generation of
      agricultural inoculants to provide more robust, more nutrient efficient, and more
      drought tolerant crop plants. However, much more knowledge is required in order
      to be able to fully exploit the potentials of fungi, to deliver what is needed
      and to address the major global challenges through new biological processes,
      products, and solutions. This knowledge can be obtained by studying the fungal
      proteome and metabolome; the biology of fungal RNA and epigenetics; protein
      expression, homologous as well as heterologous; fungal host/substrate relations;
      physiology, especially of extremophiles; and, not the least, the extent of global
      fungal biodiversity. We also need much more knowledge and understanding of how
      fungi degrade biomass in nature.The projects in our group in Aalborg University
      are examples of the basic and applied research going on to increase the
      understanding of the biology of the fungal secretome and to discover new enzymes
      and new molecular/bioinformatics tools.However, we need to put Mycology higher up
      on global agendas, e.g. by positioning Mycology as a candidate for an OECD
      Excellency Program. This could pave the way for increased funding of
      international collaboration, increased global visibility, and higher priority
      among decision makers all over the world.

PMID- 23155504
TI  - Variation in mitochondrial genome primary sequence among whole-genome-sequenced
      strains of Neurospora crassa.
AB  - Eighteen classical mutant strains of Neurospora crassa were subject to whole
      genome sequence analysis and the mitochondrial genome is analyzed. Overall, the
      mitochondrial genomes of the classical mutant strains are 99.45 to 99.98 %
      identical to the reference genome. Two-thirds of the SNPs and three-fourths of
      indels identified in this analysis are shared among more than one strain. Most of
      the limited variability in mitochondrial genome sequence is neutral with regard
      to protein structure. Despite the fact that the mitochondrial genome is present
      in multiple copies per cell, many of the polymorphisms were homozygous within
      each strain. Conversely, some polymorphisms, especially those associated with
      large scale rearrangements are only present in a fraction of the reads covering
      each region. The impact of this variation is unknown and further studies will be
      necessary to ascertain if this level of polymorphism is common among fungi and
      whether it reflects the impact of ageing cultures.

PMID- 23155505
TI  - The status of mycology in Africa: A document to promote awareness.
AB  - The African Mycological Association (AMA) promotes mycology amongst members in
      Africa and globally. The AMA has about 200 members, mostly from African states
      but also with strong representation from Europe and USA, amongst others. Recent
      efforts by members of the AMA focused on reviving and developing mycological
      research and networking in Africa. A great deal must, however, still be done to
      promote the AMA under African mycologists, and those elsewhere with interests in
      Africa. African mycologists also experience challenges typical of the developing
      world and a great deal of fungi still needs to be discovered. This can also be
      seen as representing great opportunities for research and collaboration. Several
      issues pertinent to mycology in Africa were discussed during Special Interest
      Group sessions of the 9th International Mycological Congress in 2010, and through
      several opinion pieces contributed by AMA members in the AMA newsletter,
      MycoAfrica. This contribution serves as a document to summarise these in a form
      that can be presented to fellow mycologists, biologists and other scientists,
      relevant government departments, funding bodies and Non-Governmental
      Organizations and that pins down the importance of mycology, the status thereof
      in Africa and the need to promote it more.

PMID- 23155506
TI  - FDA approves new 4-drug once-a-day HIV treatment.

PMID- 23155507
TI  - Guidance.  Interim recommendations released for physicians prescribing PrEP.

PMID- 23155508
TI  - Report.  Risky sexual behavior declines among black high schoolers.

PMID- 23155509
TI  - HIV groups against CDC recommendations for PrEP.

PMID- 23155510
TI  - Prisons.  Rights of inmate with HIV not violated by housing decision.

PMID- 23155511
TI  - Court dismisses malpractice suit for failure to provide notice.

PMID- 23155512
TI  - Anonymity.  Man's request to proceed with HIV suit anonymously denied.

PMID- 23155513
TI  - Discrimination.  Clinic chose not to hire man because of drug test, not HIV.

PMID- 23155514
TI  - Bone density and depression in premenopausal South African women: a pilot study.
AB  - OBJECTIVE: It is posited that the effect of depression on BMD is dependent on the
      severity of depression. Conflicting evidence exists regarding this possible
      association. This study investigated the association between depression and low
      bone mineral density (BMD). METHODS: The hypothesis was investigated in a random
      sample of volunteers (n=40) and in premenopausal female psychiatric patients
      (n=5) diagnosed with recurrent severe major depression. The outcome measures were
      BMD (DEXA); depression (Beck Depression Inventory and Psychological General Well
      being Scale) and 24-hour saliva cortisol levels (ELISA). In a comparison of women
      (4 of the 40 i.e. "control" subjects) with negligible symptoms of depression and
      the five patients with severe recurrent major depression- BMD, depression, saliva
      cortisol and bone turnover markers were measured and compared. Pro-inflammatory
      status (IL-1 and TNF-alpha) was investigated in the psychiatric patients only.
      RESULTS: In the random - non clinical - sample of women (n=40), 26 exhibited
      normal BDM and 14 exhibited low BMD. Drepressive symptoms and cortisol level were
      not significantly different between these two groups. Women with severe recurrent
      major depression (n=5)exhibited lower median BMD T-scores, higher overall bone
      turnover and higher 24-hour cortisol levels compared to "control" subjects (n=4).
      The psychiatric patients also exhibited elevated IL-1 levels. CONCLUSION: The
      effect of depression on BMD may be dependent on the depression severity, IL-1 and
      cortisol are possible mediators in depression-induced BMD loss.

PMID- 23155515
TI  - [Non technical skills for surgeons].

PMID- 23155516
TI  - [Role of surgeons in the patient care team in the operating rooms: ideal surgeons
      from point of view of anesthesiology].

PMID- 23155517
TI  - [Importance of peer review within hospitals].

PMID- 23155518
TI  - Board of International Affairs Pan-African Division quarterly newsletter: African
      International Division, Royal College of Psychiatrists.

PMID- 23155520
TI  - Emerging opportunities for mental health research in Africa.

PMID- 23155519
TI  - Developing services for the wandering mentally ill in an African city---the Lagos
      State example.

PMID- 23155521
TI  - When coercion meets hope: can forensic psychiatry adopt the recovery model.

PMID- 23155523
TI  - [Learning from health care system in other countries: Open Disclosure].

PMID- 23155522
TI  - [Role of the Japan Surgical Society in the achievement of surgical safety by
      surgeons].

PMID- 23155524
TI  - [Evaluation of the practice guidelines and quality indicators].

PMID- 23155525
TI  - [Practice guidelines viewed from the point of legal aspect].

PMID- 23155526
TI  - [Guidelines for patients in the delivery of health care in Japan].

PMID- 23155527
TI  - [Practice guidelines for treatment of cancers in Europe and United States].

PMID- 23155528
TI  - [Release of the Practice Guidelines for Cancer treatment].

PMID- 23155529
TI  - [Problems in the practice guidelines for treatment of cancers and future trends].

PMID- 23155530
TI  - [Statistical design in clinical trials].

PMID- 23155531
TI  - [Development of surgical assistance robots].

PMID- 23155532
TI  - [Present condition of clinical trials in surgeries for patients with lung cancer
      in Japan].

PMID- 23155533
TI  - [Present condition of clinical trials in surgeries for patients with
      hepatobiliary pancreatic lesion in Japan].

PMID- 23155534
TI  - [Multicenter randomized controlled trial in use of the synthetic absorbable
      surgical suture material for digestive system surgical procedures to prevent
      surgical wound infections].

PMID- 23155535
TI  - [Implementation of clinical trials in the field of surgery and the role of the
      periodical "Surgery Today" published in English by the Japanese Surgical
      Society].

PMID- 23155536
TI  - [One hundred years of evolution of esophageal surgical approach and clinical
      significance].
AB  - Esophageal surgery has developed for almost 100 years. Esophagectomy can be
      performed via left, right thoracotomy, even via hiatus without thoracotomy due to
      its unique anatomic characteristics. Left thoracotomy was the initial approach in
      the world, and has still been performed by Chinese colleagues, but Ivor Lewis
      (right side thoracotomy) procedure is popular in western countries. Currently,
      esophagectomy by right thoracotomy has been accepted worldwide since its radical
      dissection for tumor. Therefore, video-assisted thoracoscopic esophagectomy based
      on right thoracotomy will be the mainstream surgery for esophageal cancer in the
      future since its minimal invasion and tumor dissection.

PMID- 23155537
TI  - [Treatment of gastroesophageal reflux disease: comments from thoracic surgeon].
AB  - Gastroesophageal reflux disease (GERD) is the most common gastrointestinal
      diagnosis recorded during visits to outpatient clinics in west countries. The
      prevalence of symptom-defined GERD in China is as high as 3% to 5%. Asa
      dysfunction, GERD is characterized by reflux and heartburn. The pathophysiologic
      process of GERD is very complicated and subtle. The spectrum of injury from long
      term reflux of acid or bile includes damage mucosa, Barrett's esophagus,
      dysplasia, and esophageal cancer. Therefore, the therapies of GERD should focus
      on controlling symptom,treating complications, and surveillance the possibility
      of oncologic transform. As with therapy with proton-pump inhibitors (PPI),
      modifying lifestyle is another most important modality for most GERD. The window
      of surgical treatment for GERD is narrow. Surgical therapy is alternative
      management approach to the patients with PPI failure, complications, or huge
      hernia. The laparoscopic minimally invasive procedure improves the acceptance of
      patients to surgical therapy, but the long-term complication and drawbacks of
      anti-reflux surgery cannot be ignored, and which is even more common than open
      procedures. The limitations of current therapy for GERD have encouraged a search
      for more effective treatment.The Linx sphincter augmentation device has been
      developed to address this gap with improvement of the barrier function of LES and
      reversible design if necessary.

PMID- 23155538
TI  - Does the insanity defence lead to an abuse of human rights?

PMID- 23155539
TI  - Strengthening mental health systems.

PMID- 23155540
TI  - The prostitution of psychiatry: some are shameless, others are just easy.

PMID- 23155541
TI  - A survey of the appreciation of anaerobic infections by Venezuelan medical
      students.
AB  - The background of a successful clinical diagnosis of an anaerobic infection is
      dependent, to a large extent, on the skills, knowledge and awareness that the
      examining clinician acquired during his or her time as a medical student. To
      assess the quality of current teaching protocols in anaerobic microbiology in
      Venezuela, a survey was carried out among 300 medical students attending three
      medical schools. The survey consisted of a questionnaire of 18 questions on
      fundamental aspects of anaerobic bacteria,the infections they cause and their
      treatment. Although there was only a poor response rate (from 16% of students),
      the conclusion of the study was that there was a distinct lack of knowledge and
      appreciation of anaerobic infections among medical students in Venezuela.

PMID- 23155542
TI  - 24 hour availability of echocardiography in Acute Medicine: time to get out of
      our 'silos'.

PMID- 23155543
TI  - [Abstracts of the 6th Croatian Congress of Nephrology, Dialysis and
      Transplantation with International Participation, October 7-10, 2011, Croatia].

PMID- 23155544
TI  - [Abstracts of the 5th Symposium of the Croatian Nurses Association, Society for
      Nephrology, Dialysis and Renal Transplantation, October 7-10, 2011, Croatia].

PMID- 23155545
TI  - Menstrual regulation, unsafe abortion, and maternal health in Bangladesh.
AB  - Maternal mortality has declined considerably in Bangladesh over the past few
      decades. Some of that decline--though precisely how much cannot be quantified--is
      likely attributable to the country's menstrual regulation program,which allows
      women to establish nonpregnancy safely after a missed period and thus avoid
      recourse to unsafe abortion. Key Points. (1) Unsafe clandestine abortion persists
      in Bangladesh. In 2010, some 231,000 led to complications that were treated at
      health facilities, but another 341,000 cases were not. In all, 572,000 unsafe
      procedures led to complications that year. (2) Recourse to unsafe abortion can be
      avoided by use of the safe, government sanctioned service of menstrual regulation
      (MR)--establishing nonpregnancy after a missed period, most often using manual
      vacuum aspiration. In 2010, an estimated 653,000 women obtained MRs, a rate of 18
      per 1,000 women of reproductive age. (3) The rate at which MRs result in
      complications that are treated in facilities is one-third that of the
      complications of induced abortions--120 per 1,000 MRs vs. 357 per 1,000 induced
      abortions. (4) There is room for improvement in MR service provision, however. In
      2010, 43% of the facilities that could potentially offer it did not. Moreover,
      one-third of rural primary health care facilities did not provide the service.
      These are staffed by Family Welfare Visitors, recognized to be the backbone of
      the MR program. In addition, one-quarter of all MR clients were denied the
      procedure. (5) To assure that trends toward lower abortion-related morbidity and
      mortality continue, women need expanded access to the means of averting unsafe
      abortion. To that end, the government needs to address barriers to widespread,
      safe MR services, including women's limited knowledge of their availability, the
      reasons why facilities do not provide MRs or reject women who seek one, and the
      often poor quality of care.

PMID- 23155546
TI  - [Proceedings of the 15th Symposium of Intensive Medicine, June 27-29, 2009,
      Brijuni, Croatia].

PMID- 23155547
TI  - A long and winding road: federally qualified health centers, community variation
      and prospects under reform.
AB  - Community health centers have evolved from fringe providers to mainstays of many
      local health care systems. Those designated as federally qualified health centers
      (FQHCs), in particular, have largely established themselves as key providers of
      comprehensive, efficient, high-quality primary care services to low-income
      people, especially Medicaid and uninsured patients. The Center for Studying
      Health System Change's (HSC's) site visits to 12 nationally representative
      metropolitan communities since 1996 document substantial growth in FQHC capacity,
      based on growing numbers of Medicaid enrollees and uninsured people, increased
      federal support, and improved managerial acumen. At the same time, FQHC
      development has varied considerably across communities because of several
      important factors, including local health system characteristics and financial
      and political support at federal, state and local levels. Some communities-
      Boston; Syracuse, N.Y.; Miami; and Seattle--have relatively extensive FQHC
      capacity for their Medicaid and uninsured populations, while other communities-
      Lansing, Mich.; northern New Jersey; Indianapolis; and Greenville, S.C.--fall in
      the middle. FQHC growth in Phoenix; Little Rock, Ark.; Cleveland; and Orange
      County, Calif.; has lagged in comparison. Today, FQHCs seem poised to play a key
      role in federal health care reform, including coverage expansions and the
      emphasis on primary care and medical homes.

PMID- 23155548
TI  - [Proceedings of 6th Croatian Congress on Emergency Medicine with international
      participation, November 19-20, 2009, Zagreb, Croatia].

PMID- 23155549
TI  - Limited options to manage specialty drug spending.
AB  - Spending on specialty drugs--typically high-cost biologic medications to treat
      complex medical conditions--is growing at a high rate and represents an
      increasing share of U.S. pharmaceutical spending and overall health spending.
      Absence of generic substitutes, or even brand-name therapeutic equivalents in
      many cases, gives drug manufacturers near-monopoly pricing power and makes
      conventional tools of benefit design and utilization management less effective,
      according to a new qualitative study from the Center for Studying Health System
      Change (HSC). Despite the dearth of substitutes, cost pressures have prompted
      some employers to increase patient cost sharing for specialty drugs. Some believe
      this is counter-productive, since it can expose patients to large financial
      obligations and may reduce patient adherence, which in turn may lead to higher
      costs. Utilization management has focused on prior authorization and quantity
      limits, rather than step-therapy approaches--where lower-cost options must first
      be tried--that are prevalent with conventional drugs. Unlike conventional drugs,
      a substantial share of specialty drugs--typically clinician-administered drugs-
      are covered under the medical benefit rather than the pharmacy benefit. The
      challenges of such coverage--high drug mark-ups by physicians, less utilization
      data, less control for health plans and employers--have led to attempts to
      integrate medical and pharmacy benefits, but such efforts are still in early
      development. Health plans are experimenting with a range of innovations to
      control spending, but the most meaningful, wide-ranging innovations may not be
      feasible until substitutes, such as biosimilars, become widely available, which
      for many specialty drugs will not occur for many years.

PMID- 23155550
TI  - Emergency preparedness and community coalitions: opportunities and challenges.
AB  - Being prepared for a natural disaster, infectious disease outbreak or other
      emergency where many injured or ill people need medical care while maintaining
      ongoing operations is a significant challenge for local health systems. Emergency
      preparedness requires coordination of diverse entities at the local, regional and
      national levels. Given the diversity of stakeholders, fragmentation of local
      health care systems and limited resources, developing and sustaining broad
      community coalitions focused on emergency preparedness is difficult. While some
      stakeholders, such as hospitals and local emergency medical services,
      consistently work together, other important groups--for example, primary care
      clinicians and nursing homes--typically do not participate in emergency
      preparedness coalitions, according to a new qualitative study of 10 U.S.
      communities by the Center for Studying Health System Change (HSC). Challenges to
      developing and sustaining community coalitions may reflect the structure of
      preparedness activities, which are typically administered by designated staff in
      hospitals or large medical practices. There are two general approaches policy
      makers could consider to broaden participation in emergency-preparedness
      coalitions: providing incentives for more stakeholders to join existing
      coalitions or building preparedness into activities providers already are
      pursuing. Moreover, rather than defining and measuring processes associated with
      collaboration--such as coalition membership or development of certain planning
      documents--policy makers might consider defining the outcomes expected of a
      successful collaboration in the event of a disaster, without regard to the
      specific form that collaboration takes.

PMID- 23155551
TI  - Medicare and Medicaid programs: Hospital Outpatient Prospective Payment and
      Ambulatory Surgical Center Payment Systems and Quality Reporting Programs;
      electronic reporting pilot; Inpatient Rehabilitation Facilities Quality Reporting
      Program; revision to Quality Improvement Organization regulations. Final rule
      with comment period.
AB  - This final rule with comment period revises the Medicare hospital outpatient
      prospective payment system (OPPS) and the Medicare ambulatory surgical center
      (ASC) payment system for CY 2013 to implement applicable statutory requirements
      and changes arising from our continuing experience with these systems. In this
      final rule with comment period, we describe the changes to the amounts and
      factors used to determine the payment rates for Medicare services paid under the
      OPPS and those paid under the ASC payment system. In addition, this final rule
      with comment period updates and refines the requirements for the Hospital
      Outpatient Quality Reporting (OQR) Program, the ASC Quality Reporting (ASCQR)
      Program, and the Inpatient Rehabilitation Facility (IRF) Quality Reporting
      Program. We are continuing the electronic reporting pilot for the Electronic
      Health Record (EHR) Incentive Program, and revising the various regulations
      governing Quality Improvement Organizations (QIOs), including the secure
      transmittal of electronic medical information, beneficiary complaint resolution
      and notification processes, and technical changes. The technical changes to the
      QIO regulations reflect CMS' commitment to the general principles of the
      President's Executive Order on Regulatory Reform, Executive Order 13563 (January
      18, 2011).

PMID- 23155552
TI  - Medicare program; revisions to payment policies under the physician fee schedule,
      DME face-to-face encounters, elimination of the requirement for termination of
      non-random prepayment complex medical review and other revisions to Part B for CY
      2013. Final rule with comment period.
AB  - This major final rule with comment period addresses changes to the physician fee
      schedule, payments for Part B drugs, and other Medicare Part B payment policies
      to ensure that our payment systems are updated to reflect changes in medical
      practice and the relative value of services. It also implements provisions of the
      Affordable Care Act by establishing a face-to-face encounter as a condition of
      payment for certain durable medical equipment (DME) items. In addition, it
      implements statutory changes regarding the termination of non-random prepayment
      review. This final rule with comment period also includes a discussion in the
      Supplementary Information regarding various programs . (See the Table of Contents
      for a listing of the specific issues addressed in this final rule with comment
      period.)

PMID- 23155553
TI  - Regulation. Is scrutiny of care poorer the further you are from London?

PMID- 23155554
TI  - Equality. The unplanned racist impact of reform.

PMID- 23155555
TI  - Trust chiefs fear regulators would not spot scandal.

PMID- 23155557
TI  - Easton: we must tackle cost-cutting masked as efficiency.

PMID- 23155556
TI  - Data quality concerns delay mental health tariff.

PMID- 23155558
TI  - CCG budgets face complications, says DH.

PMID- 23155559
TI  - The argument over NHS competition isn't settled yet.

PMID- 23155560
TI  - Darzi and Howitt international healthcare. NHS must grasp a world of opportunity.

PMID- 23155561
TI  - Beyond inspections.

PMID- 23155562
TI  - Playing fair on treatments.

PMID- 23155563
TI  - Public health. Change of heart.

PMID- 23155564
TI  - Medicines management. Put it in the recycling bin.

PMID- 23155565
TI  - Service improvement. Falling through the cracks.

PMID- 23155566
TI  - Innovation switched on.

PMID- 23155567
TI  - Innovation: case studies. Trials in the real world.

PMID- 23155568
TI  - Commissioning. Now for the hard bit.

PMID- 23155569
TI  - Guidance. Tackling the 'mindset problem'.

PMID- 23155570
TI  - Case study. Risk and reward.

PMID- 23155571
TI  - Infertility. How to avoid stretch marks on your budget.

PMID- 23155572
TI  - Clinical leaders. The move from medic to manager.

PMID- 23155573
TI  - Patient safety. The way ahead for whistleblowing.

PMID- 23155574
TI  - Performance. Getting the most out of out of area.

PMID- 23155575
TI  - Integrative review of nursing research: scientific rigor required.

PMID- 23155576
TI  - [Nursing care for patients undergoing pharmacological stress echocardiography:
      implications for clinical practice].
AB  - The study aim was both to identify signs and symptoms previous to and during the
      pharmacological stress echocardiography test and to describe the nurse's role and
      nursing care principles for this exam. This is a descriptive study, carried out
      in cardiac care unit in a University Hospital in Porto Alegre, RS. Two hundred
      forty-six records of patients submitted to stress echocardiography were
      retrospectively reviewed, according to four different pharmacological schedules.
      The statistical comparison showed that signs and symptoms were related to the
      type of drug used during the exam, namely: typical angina, precordial ache,
      tiredness, headache and premature complexes. These results enabled a better
      understanding of pharmacological stress echocardiography and the
      instrumentalization of nurses in order to plan individualized and qualified
      nursing care assistance. Aside from helping develop nursing practices for the
      pharmacological stress echocardiography test this knowledge could also be used by
      nurses who carry out their activities in institutions that use this diagnostic
      method.

PMID- 23155577
TI  - [Educational activities for people with chronic disease: grants for nursing].
AB  - This is an intervention study conducted in a Unidade Basica de Saude (Basic
      Health Unit) in Colombo, Parana, Brazil from March to November 2009, with 35
      carriers of chronic diseases aged between 18 and 60 years, and enrolled in the
      Hypertension and Diabetes Program. The objectives were to identify their
      knowledge about arterial hypertension and act through educational group
      activities. Data were collected though semistructured interviews and four group
      meetings, and the following categories emerged from the analysis: "Understanding
      of the disease" and "Ways of caring". It was found that users knew the disease,
      its risk factors and possible complications, and that educational activities
      favored the sharing of experiences,provided reflection and the possibility of
      treatment management. This is a strategy that should be used and promoted by
      nurses.

PMID- 23155578
TI  - [Assessment of quality of nursing prescriptions in public teaching hospital].
AB  - A multicenter, cross-sectional study took place from December 2009 to June 2010
      and aimed to assess the quality of Nursing Prescription (NP) in two public
      teaching hospitals. The sample consisted of 1,307 NP and data were processed
      using the G-test and chi-square. The determination of the quality of NP was based
      on the classification indices reported in literature. Among the results, 1,083
      (82.8%) correct and appropriate NP, 154 (11.8%) inadequate NP and 52 (3.9%)
      incomplete NP were found. In 18 (1.37%) patient charts, the NP was nonexistent.
      There was statistic signficance (alpha < 0.05) for incomplete and absent NP
      between the two hospitals (0.00), as well as inappropriate NP between age groups
      (0.03). It was concluded that, in the hospitals under study, the NP needs to be
      improved both in terms of quantity and quality.

PMID- 23155579
TI  - [Nurse's assessment of oral health of elderly people: OHAT validity and
      reliability].
AB  - The aim of the study was to apply the Oral Health Assessment Tool (OHAT)for
      determination of the reliability and validity indexes, when utilized by nursing
      staff The OHAT was administered to 50 elderly individuals. The exams were
      performed in different periods of times by a Nurse and a Dental Surgeon (DS). The
      determination of internal consistency was verified through Cronbach's Alpha
      Coeficient and ANOVA. For the determination of stability and reliability, the
      percentage agreement and Kappa test were considered. There was no statistical
      difference among the final averages obtained by the DS and the nurse (p=0.41).
      There was a higher internal consistency in the exams performed by the DS. The
      Kappa value of the instrument reached 0.46, being considered moderate. The OHAT
      instrument can be used by nurses as a screening tool however, previous training
      is needed for criteria standardization.

PMID- 23155580
TI  - [Characteristics of victims and fatal accidents at the workplace].
AB  - This is a quantitative, descriptive, retrospective documental study on fatal
      accidents occurred during the period from o2006 to 2010, in which workers were
      treated at Hospital do Trabalhador, located in Curitiba/Parand. We selected 25
      notifications for the outcome death. This study aimed to characterize victims and
      fatal occupational accidents. Fatal occupational accidents hit workers with a
      mean age of 35 years (SD = 13.0694), of the male sex, n = 23 (92%). Typical
      occupational accidents accounted for 52% (n = 13) of cases. One of the preventive
      measures proposed to reduce the number of fatal occupational accidents is the
      performance of educational and preventive work at the workplace by nurses.
      Moreover, it is necessary to rethink transit violence as a relevant factor for
      the cause of death of workers as well.

PMID- 23155581
TI  - [Classification of patients in a traumatology unit].
AB  - Study with the aim to classify patients in accordance with the degree of
      dependence on nursing care, estimate the size of the nursing staff and correlate
      instruments. Perroca and Fugulin's instruments were used to classify patients
      admitted for a period of 30 days and to estimate the size of the nursing staff
      the formula recommended by the Federal Nursing Board COFEN No. 293/0 was used.
      Included were 157 patients, 42.0% were classified as dependent on intermediate
      care, and for 50.3% of patients, the degree of dependence zas classified as
      minimum care. Regarding the size of the nursing staff the existing staff in the
      surveyed unit consisted of 20 employees, while the necessary size should be 32
      employees, divided in thefour shifts. The instruments showed a strong correlation
      (rp=0.88). It is believed that the classification of patients in order to
      estimate the size of the nursing team can provide more quality to care.

PMID- 23155582
TI  - [Heavy alcohol consumption among women].
AB  - This descriptive, exploratory study aimed to characterize women attending a
      Teaching Hospital in Northwest Parana, for alcohol abuse in the years 1999 to
      200, according to sociodemographic data of intoxication and associated with
      trauma and violence. Among 823 visits, the most frequent age range was from 20 to
      49 years (58.32%). 13 (1.58%) were pregnant, 12.5% had 9-12 years of schooling.
      Liquor was the main beverage used and its intake was more prevalent at night.
      Approximately 156 (18.96%) women required hospitalization. Hospital avoidance was
      observed in 8.5% of cases. We conclude that woman are likely to abuse alcohol,
      and this study enabled a description of the areas in women's health that are
      impacted allowing the implementation of preventive measures to decrease
      occurrence and recurrence in this population.

PMID- 23155583
TI  - [Educational strategy addressed to nurses in primary care for infertility: an
      intervention study].
AB  - The objective was to assess the impact of an educational strategy approaching
      infertility assistance; and verify practices introduced into the daily work of
      the participants after this intervention. Research-action developed with 11
      nurses from the Family Health Strategy, in Fortaleza-CE, through the reading of a
      brochure in a "circle of conversation." Data were collected in August and October
      2010, before, immediately after and 60 days after the intervention. An increase
      in the levels of knowledge was noted immediately after the intervention, when all
      participants had a "more than good" or "very good" level of knowledge, leaving
      behind the "little" and "good" levels rated before the intervention; at 60 days,
      a "good" level of knowledge was noted again, showing a relative decrease in
      knowledge. There was self-recognition of the ability to introduce practices into
      the daily work after the intervention, confirming the positive impact thereof

PMID- 23155584
TI  - [Occupational stress: evaluation of intensive care nurses who work at nighttime].
AB  - Descriptive, cross-sectional study, which aimed to evaluate the stress level of
      nighttime intensive care nurses. The Bianchi Stress Scale was applied to 26
      (100%) nurses from five hospitals. In data analysis, the Pearson Chi-square test
      was used and it was noticed that the stress among nurses in a public (3.36
      points) and private facility (3.02 points) was classified at the median level and
      there was no statistical significance (p = 0.90) forr stress, according to the
      type of institution. Variables that most contributed to the occurrence of stress
      were: working conditions (nighttime work closed and critical unit), patient
      severity, management activities associated with care. It was concluded that the
      workplace was positively associated with the stress in nurses working at
      nighttime and that its onset and effects can be minimized through improvements in
      the structure and organization of the place where the healthcare providers work.

PMID- 23155585
TI  - [Maternal risk factors for premature births in a public maternity hospital in
      Imperatriz-MA].
AB  - Despite advances in obstetrics, prematurity is still a major public health
      problem because of the neonatal morbidity and mortality it causes. The objective
      of this study was to investigate maternal risk factorsfor premature births in a
      public maternity in the city of Imperatriz-MA. A cross-sectional comparative
      study was conducted with 116 mothers, through structured interviews. The data
      were analyzed using Epi-Info version 3.5.1. The variables that showed
      statistically significant association with preterm delivery were monthly income
      below two minimum wages (p = 0.046), stress during pregnancy (p = 0.027),
      primiparity (p = 0.044), absent or inadequate prenatal care (p <0.001) and
      clinical complications in pregnancy (p<0.001). The results show that the maternal
      risk factors implicated in prematurity are related mainly with lifestyle,
      socioeconomic and clinical variables, and prenatal care.

PMID- 23155586
TI  - [Educational geronto-technology for ostomized seniors from a complexity
      perspective].
AB  - We aimed to present the educational booklet as a geronto-technological product
      for caring for ostomized seniors from a complexity perspective. This was
      accomplished in the second semester of 2007 in a hospital in the south of Brazil.
      The data were collected through interviews and presented in the form of an
      educational booklet. The booklet was validated by ostomized seniors and by a
      nurse who had been working with these elderly patients. The booklet was presented
      as a geronto-technology able to help ostomized seniors and their families
      understand the rights of ostomized people; concepts and types of stomas; care of
      ostomy; and the importance of the family and the support group for care. In
      conclusion, the educational booklet is presented as a health promotion tool which
      makes the health educative process easier.

PMID- 23155587
TI  - [Support group as a strategy of care: the importance for relatives of drug
      users].
AB  - The objective was to investigate the perception by relatives of drug users about
      the importance of the support group as a strategy of care. We conducted a
      descriptive study with qualitative approach, in the second half of 2010, in a
      psychosocial care center for users of alcohol and other drugs (CAPS AD), in a
      city in the extreme south of Brazil with ten relatives. Data were collected by
      semistructured interviews and analyzed by thematic analysis. It was found that
      the group is an alternative to hospitalization in a psychiatric hospital, can
      provide access and regular monitoring by health professionals, helps understand
      what addiction is, provides tools for care and allows for the social
      rehabilitation of the addict. The support group was concluded to be an important
      strategy for caring for relatives of drug users, presenting itself as a
      technology to be incorporated by nurses in their daily practice.

PMID- 23155588
TI  - [Men and women living in marital violence: socioeconomic aspects].
AB  - Quantitative and descriptive study aiming to identify socioeconomic
      characteristics of men and women with a history of domestic violence. We
      conducted interviews with 50 men and 50 women. Nearly all subjects were self
      declared black. Most did not have too many years of school education. Men perform
      occupations that are public and women do predominantly domestic activities. Only
      3 women (6%) are considered financially independent. The degree of economic
      dependence is directly related to the level of education that has been
      established as a prerequisite to enter into the labor market. The situation is
      even more precarious for women interviewed with fewer years of education and a
      high degree of financial dependence that interferes with their empowerment to
      address domestic violence. Health professionals, especially nurses, should
      address the social inequities and improve the socioeconomic context of users to
      identify situations that endanger the health of the population.

PMID- 23155589
TI  - [Identification of the nursing diagnosis of fall risk in elderly with stroke].
AB  - The purpose of this study was to verify the presence of a nursing diagnosis of
      fall risk in elderly with stroke. Observational exploratory and cross-sectional
      study with descrziptive analysis. Performed in a charitable rehabilitation
      association in Fortaleza city, from January to March 2010, by primary source, by
      interviews and physical examination with elderly people who had at least one
      episode of stroke 37 individuals participated of which 20 (54.1%) were women,
      with mean age of 70.6years, and 18 (48.6%) lived with a partner and had an
      average of 5.2 years of study. The risk of falls was found in all elderly. Among
      the risk factors identified it is possible to highlight Impaired balance (100%),
      Age above 65 years (83.7%), and Proprioceptive deficit (83.7%). Nurses must
      consider the risk of falls as a nursing carefocus and implement and evaluate the
      results of interventions for fall prevention.

PMID- 23155590
TI  - [Instrument to collect data for critical patients based on the theory of basic
      human needs].
AB  - This is an exploratory study based on qualitative approach that aimed to
      collectively construct an instrument to collect data for patients in the
      Intensive Care Unit (ICU), based on the Theory of Basic Human Needs (NHB). Data
      collection was through a focus group with four nurses from the ICU and four
      residents from the Nursing-Health Integrated Residency (RIS) program in seven
      meetings in 2009. The discussions produced in each session were analyzed as
      recommended by Horta. The instrument was divided into seven groups and 17
      subgroups of needs. After testing and suggestions from participants, we
      elaborated the final version of the instrument and a guidance manualfor
      completing it, according to the need expressed by the group. Validation of the
      instrument and the manual and inclusion of teaching of the nursing process in the
      RIS activity program are suggested.

PMID- 23155591
TI  - [Option and evasion of a bachelor's degree programme in nursing evaded students'
      perception].
AB  - Qualitative study, developed in a Federal University in southern Brazil aiming to
      know the motives for choosing and evading a Bachelor's degree programme in
      Nursing, in the evaded students 'perception. The data were collected through a
      questionnaire sent by e-mail to 19 evaded students. The 9 questionnaires that
      returned were submitted to Qualitative Textual Analysis, and two categories
      emerged motives to opt for the nursing programme and motives to evade from the
      nursing programme. The results showed that the option for the programme is
      associated to personal vocation, perception of Nursing as a profession of care,
      and its closeness to the health area. Evasion seems to be related to passing the
      first option of undergraduate programme, ignorance about the profession,
      financial difficulties, and professional depreciation. We demonstrated that
      greater emphasis should be put on promoting knowledge about the nursing work,
      areas of activity and attributions.

PMID- 23155592
TI  - [Patients living with HIV/AIDS and co-infection by tuberculosis: difficulties
      associated with treatment compliance or dropout].
AB  - Research carried out in Fortaleza-CE, between March and April 2011, with the
      objective of describing the difficulties that influence non-compliance to
      tuberculosis treatment or treatment dropout in patients infected with Human
      Immunodeficiency Virus. Qualitative study with data collected through a semi
      structured interview, applied to patients with acquired immunodeficiency syndrome
      and with co-infection of tuberculosis. The Collective Subject's Speech was used
      for result analysis. Patients reported difficulties related to socioeconomic
      aspects, lifestyle and drug use. The consumption of alcohol and illicit drugs
      were factors that led to the discontinuance of the therapeutic process of the
      disease. We conclude that the barriers related to social economical aspects and
      to lifestyle are more difficult to be faced for a continuous compliance to
      treatment, making the role played by health professionals necessary, supported by
      more effective public and social policies.

PMID- 23155593
TI  - [Users' perceptions of urgency and reasons for using the mobile pre-hospital care
      service].
AB  - The Mobile Emergency Care Services handle urgent situations of various types, and
      demand for this service occurs according to the perception of the user regarding
      what is urgent. The aim of the study was to analyze the perceptions of urgency by
      users who demand care from a Mobile Emergency Care Service in Porto Alegre and to
      identify the reasons for these requests. In this explomratory-descriptive study,
      with qualitative approach, data were collected through semi-structured interviews
      conducted by telephone, during theperiod from February to April 2009. Thematic
      analysis was used to analyze the information. Users consider urgent life
      threatening conditions, which require a quick response, and visible situations,
      such as bleeding, chronic diseases, and difficulties in transportation. Users
      themselves feel motivated to call the service due to it being rapid and free, and
      for transportation. The perceptions of users regarding urgency were diverse,
      sometimes consistent with the biomedical perspective of health providers and
      sometimes with their own social context.

PMID- 23155594
TI  - [Pleasure in nursing technicians working at an emergency unit of a public
      university hospital].
AB  - This study aimed to reveal the main aspects of the work process and feelings of
      pleasure experienced by nursing technicians who work at an emergency unit in
      Parana, Brazil. The theoretical basis is the psychodynamics of work. This is a
      qualitative and descriptive study. Data were collected and analyzed using a semi
      structured interview and the content analysis technique. Subjects were selected
      using a snowball sampling. Important aspects of the work process were revealed
      such as the unpredictability of working in an emergency unit, the impact of team
      work, and the comprehensive care model as a precursor to humanized care. Pleasure
      originates from the acknowledgement of their work either by the working subject
      him/herself by patients or society; and from the team work, realized by the
      cooperation among professionals. Feelings of pleasure are linked to the
      acknowledgment of their work, which should be valued since gratification
      contributes to the psychological health of workers.

PMID- 23155595
TI  - [Assessment of body weight changes in patients on peritoneal dialysis].
AB  - This study had as its main objective to assess the variation in body weight of
      patients on peritoneal dialysis (DP) during the first year of treatment and as a
      secondary goal to identify patients with criteria for metabolic syndrome (SM).
      Observational study conducted with 35 patients of a university hospital. Data
      were collected on the clinical and demographic status, change of body weight and
      criteria for SM from the sample. After 12 months of initiation of dialysis,
      approximately 40% of patients showed overweight and/or obesity. The average
      variation of body weight after one year was 3.7 Kg, and the largest variation was
      found in the first three months, with values of 2.2 Kg The prevalence of SM was
      30%. It was concluded that the most important change of body weight happened in
      the first year of treatment and there is a high prevalence of SM in patients on
      DP.

PMID- 23155596
TI  - [Occupational violence experienced by nursing staff in hospital emergency
      service].
AB  - This research objectives were: to discover the sociodemographic profile of the
      nursing staff that works in the hospital emergency service, identify the main
      types of occupational violence suffered by this team. Cross-sectional descriptive
      study done in a general hospital in Duque de Cazxias/Rio de Janeiro. The data,
      collected on August, 2009, was put in tables for subsequent univariate analysis.
      The sample of respondents comprised 30 workers. The analyzed data showed that the
      majority of employees interviewed were victims of occupational violence (76.7%).
      The main causes of occupational violence were the companions (87.0%) followed by
      patients (52.2%). The more frequentform of aggression was verbal aggression
      (100.0%). The results showed that these workers have little expectation on
      changing the current situation and do not believe that their managers can assist
      them in the problem.

PMID- 23155597
TI  - [Functional capacity in elderly longevity: an integrative review].
AB  - This is an integrated literature review intended to get to know the Brazilian
      scientific production regarding the functional capacity of the elderly. BDENF,
      LILACS, MEDLINE and SciELO databases were consulted in the sampling period from
      January, 2001, to September, 2010. Eight articles were selected with nursing
      professionals (4) as the main authors of such publications. Publication year of
      the articles is between 2006 and 2010, with predomination of quantitative
      research focused on the multidimensionality of the elderly. Questionnaires and
      scales were used to assess the functional capacity of the elderly and
      constraining factors for its performance were also indicated. Scientific studies
      on the theme are incipient, which evidences the need for further research aiming
      to improve the quality of life of the elderly.

PMID- 23155598
TI  - [Patient education on drug treatment regimen in the process of hospital
      discharge: an integrative review].
AB  - Adequate patient education about drug treatment regimen at discharge contributes
      to the continuity of home care. Integrative review aimed to analyze and
      synthesize the scientific literature about patient education on medication
      regimen in the hospital discharge process. We consulted the databases Medical
      Literature Analysis and Retrieval System on-line (MEDLINE) and Latin-American and
      Caribbean Center on Health Sciences Information (LILACS), and selected 24
      articles published between 2005 and 2010. Inter-related aspects, such as
      structured discharge planning, medication reconciliation, drug education, adverse
      drug events and medication adherence, permeate the theme.

PMID- 23155599
TI  - [Montessori method applied to dementia - literature review].
AB  - The Montessori method was initially applied to children, but now it has also been
      applied to people with dementia. The purpose of this study is to systematically
      review the research on the effectiveness of this method using Medical Literature
      Analysis and Retrieval System Online (Medline) with the keywords dementia and
      Montessori method. We selected lo studies, in which there were significant
      improvements in participation and constructive engagement, and reduction of
      negative affects and passive engagement. Nevertheless, systematic reviews about
      this non-pharmacological intervention in dementia rate this method as weak in
      terms of effectiveness. This apparent discrepancy can be explained because the
      Montessori method may have, in fact, a small influence on dimensions such as
      behavioral problems, or because there is no research about this method with high
      levels of control, such as the presence of several control groups or a double
      blind study.

PMID- 23155600
TI  - [Risk and vulnerability in the practice of professional healthcare].
AB  - The purpose of this study is to analyze the risks and vulnerability found in
      professional healthcare and the safe practices adopted based on academic research
      in the field of healthcare and nursing, by means of an integrative review. The
      articles were found in the LILACS and SCIELO databases,from the years 2005-2010,
      in a search for the descriptors vulnerability, risk, and occupational and
      personal health risks, establishing a sample of 21 articles. In basic healthcare,
      risks and vulnerabilities are related to the lack of resources needed for work,
      physical violence and emotional strain. In a hospital context, the problems are
      related to accidents with biological materials caused by improper use and failure
      to adopt protective measures, as well as excessive work and self-confidence. The
      importance of implementing public policies in worker health to improve working
      conditions and provide greater satisfaction and professional awareness is
      emphasized.

PMID- 23155601
TI  - Myths about stroke--on the road to change.

PMID- 23155602
TI  - [Prevalence of overweight and obesity in adult rural population of the northern
      part of Backa and Banat].
AB  - BACKGROUND/AIM: Obesity represents one of the frequent health problems in
      developed countries today. It is related to cardiovascular diseases, diabetes and
      various cancer forms. The aim of the study was to determine the prevalence of
      overweight and obesity in adult population of the northern Badka and Banat.
      METHODS: On the basis of a multistage stratified random sampling, 4505
      individuals of the age 40.61 +/- 11.29 years took part in the study. The study
      included 46 rural settlements. The overweight and obesity prevalence was obtained
      using the anthropometric indicators of body mass index (BMI), waist circumference
      (WC) and the waist to hip ratio (WHR). The correlations among BMI, WC and WHR
      were determined by the Pearson's correlation coefficient while the multiple
      regression analysis was used for correlating sociodemographic parameters and the
      obesity index. RESULTS: A significant positive correlation was found in relation
      to all anthropometric parameters in both sexes. The data indicated that 66.32% of
      males and 49.68% of females had an overweight problem. On average, approximately
      38.52% of subjects of both sexes were overweight, while 19.48% were obese. The
      factors that largely contributed to higher values of the obesity index were the
      age of male subjects and the age, education and origin in females. Ragarding the
      female subjects, the level of education negatively correlated with the level of
      nutritional condition. CONCLUSION: The prevalence values of the overweight and
      obese subjects, obtained on the basis of the anthropometric parameters, vary.
      However, regardless methods applied, the percentage of the overweight and obese
      persons is very high, being among the highest recorded in European populations.
      The obtained results indicate the necessity of introducing better education
      programmes and conducting regular health controls among citizens in these
      regions.

PMID- 23155603
TI  - Prevalence of renal dysfunction and its influence on functional capacity in
      elderly patients with stable chronic heart failure.
AB  - BACKGROUND/AIM: Chronic heart failure (CHF) is highly prevalent and constitutes
      an important public health problem around the world. In spite of a large number
      of pharmacological agents that successfully decrease mortality in CHF, the
      effects on exercise tolerance and quality of life are modest. Renal dysfunction
      is extremely common in patients with CHF and it is strongly related not only to
      increased mortality and morbidity but to a significant decrease in exercise
      tolerance, as well. The aim of our study was to investigate the prevalence and
      influence of the renal dysfunction on functional capacity in the elderly CHF
      patients. METHODS: We included 127 patients aged over 65 years in a stable phase
      of CHF. The diagnosis of heart failure was based on the latest diagnostic
      principles of the European Society of Cardiology. The estimated glomerular
      filtration rate (eGRF) was determined by the abbreviated modification of diet in
      renal disease (MDRD2) formula, and patients were categorized using the kidney
      disease outcomes quality initiative (K/DOQI) classification system. Functional
      capacity was determined by the 6 minute walking test (6MWT). RESULTS: Among 127
      patients, 90 were men. The average age was 72.5 +/- 4.99 years and left
      ventricular ejection fraction (LVEF) was 40.22 +/- 9.89%. The average duration of
      CHF was 3.79 +/- 4.84 years. Ninty three (73.2%) patients were in New York Heart
      Association (NYHA) class II and 34 (26.8%) in NYHA class III. Normal renal
      function (eGFR > or = 90 mL/min) had 8.9% of participants, 57.8% had eGFR between
      60-89 mL/min (stage 2 or mild reduction in GFR according to K/DOQI
      classification), 32.2% had eGFR between 30-59 mL/min (stage 3 or moderate
      reduction in GFR) and 1.1% had eGFR between 15-29 mL/min (stage 4 or severe
      reduction in GFR). We found statistically significant correlation between eGFR
      and 6 minute walking distance (6MWD) (r = 0.390, p < 0.001), LVEF (r = 0.268, p <
      0.05), NYHA class (p = -0.269, p < 0.05) and age (r = 0.214, p < 0.05). In
      multiple regression analysis only patients' age was a predictor of decreased 6MWD
      < 300 m (OR = 0.8736, CI = 0.7804 - 0.9781, p < 0.05). CONCLUSION: Renal
      dysfunction is highly prevalent in the elderly CHF patients. It is associated
      with decreased functional capacity and therefore with poor prognosis. This study
      corroborates the use of eGFR not only as a powerful predictor of mortality in
      CHF, but also as an indicator of the functional capacity of cardiopulmonary
      system. However, clinicians underestimate a serial measurement of eGFR while it
      should be the part of a routine evaluation performed in every patient with CHF,
      particularly in the elderly population.

PMID- 23155604
TI  - [Reading characteristics of deaf and hard-of-hearing pupils].
AB  - BACKGROUND/AIM: Speech motor mechanisms play a crucial role in the process of
      demutization, due to the fact that they cover all the elements of the successive
      development of spech production movements leading to speech formation (so-called
      kinesthesia in speach). The aim of this study was to estimate the impact of
      perceptual motor actions on the cognitive process of reading in 130 students in
      regular schools and schools for the deaf and hard-of-hearing children in the
      Republic of Serbia. METHODS: Kostic and Vladisavljevic test consisted of the ten
      levels weight was used for the assessment of reading speed. To assess
      understanding of text read by verbal responses, we used three-dimensional adapted
      reading test of Helene Sax. RESULTS: The triage-articulation test for assessing
      reading speed (Kostie and Vladisavljevic's test according to the weight of ten
      levels, revealed that students in regular schools statistically significantly
      faster read texts as compared to the deaf students. The results of the three
      dimensional adapted reading test of Helena Sax, show that the words learned by
      deaf children exist in isolation in their mind, i.e., if there is no standard of
      acoustic performance for graphic image, in deaf child every word, printed or
      written, is just the sum of letters without meaning. CONCLUSION: There is a
      significant difference in text reading speed and its understanding among the
      children who hear and the deaf and hard-of-hearing children. It is essential that
      in deaf and heard-of-hearing children education, apart from the development of
      speech, parallelly use the concept of semantic processing in order to get each
      word by the fullness of its content and the possibility of expanding its meaning
      in a variety of assets.

PMID- 23155605
TI  - [Photorefractive keratectomy for correction of myopia--our one-year experience].
AB  - BACKGROUND/AIM: Photorefractive keratectomy (PRK), after laser in situ
      keratomileusis (LASIK), is commonly performed refractive surgical method
      worldwide. The aim of this study was to examine the effectiveness and safety of
      PRK in correction of various strengths of myopia and to assess how much corneal
      tissue is being removed with one diopter sphere (Dsph) correction by using
      different optical zones (OZ). METHODS: A prospective study with a follow-up
      period of 6 months included 55 patients of which 100 myopic eyes were treated by
      PRIK method (one eye was included in 10 patients). Myopic eyes with a
      preoperative best corrected visual acuity (BCVA) = 1.0 (20/20) were analysed. In
      order to assess the effectiveness of PRK operated myopic eyes were divided into
      four groups according to the dioptric power: (1) < or = -1.75 Dsph (n=26); 2)
      from -2 to -3.75 Dsph (n=44); 3) from -4 to -6.75 Dsph (n=23), and 4) > or = -7
      Dsph (n=7). Myopic eyes with preoperative BCVA < or = 0.9 (amblyopic eyes) were
      excluded from the study, as well as eyes with astigmatism > -1.5 Dcyl. To assess
      the effectiveness of PRK we examined the percentage of eyes in the mentioned
      groups, which derived uncorrected visual acuity (UCVA) 6 months after the
      intervention to the following: (a) UCVA = 1.0 (20/20) and (b) UCVA > or = 0.5
      (20/40). To assess the safety of PRK we examined the frequency of intraoperative
      and postoperative complications. To estimate how much corneal tissue was removed
      with one Dsph correction by using different OZ, we used preoperative and
      postoperative (after 6 months) central pachymetry values expressed in microm and
      volume of cornea (central 7 mm) expressed in mm3. In that sense, we used only the
      myopic eyes with clear preoperative spherical refraction. The total number of
      these eyes was 27, of which 16 eyes were treated using a 6.5 mm OZ and 11 eyes
      using a 7 mm OZ. RESULTS: Refractive spherical equivalent (RSE) for all eyes was
      in the range from -0.75 to -8.75 Dsph, and preoperative mean value of RSE with
      standard deviation (mean RSE +/- SD) was -3.32 +/- 1.83 Dsph. Six months after
      PRK, 91% of eyes had UCVA = 20/20, and 99% of eyes had UCVA > or = 20/40. In the
      first group (< or = -1.75 Dsph) preoperative mean RSE +/- SD was -1.34 +/- 0.32
      Dsph, six months after PRK, 96% of eyes had UCVA = 20/20, and 100% of eyes had
      UCVA > or = 20/40. In the second group (from -2 to -3.75 Dsph) preoperative mean
      RSE +/- SD was - 2.95 +/- 0.57 Dsph, six months after PRK, 89% of eyes had UCVA =
      20/20, and 100% of eyes had UCVA > or = 20/40. In the third group (from -4 to 
      6.75 Dsph) preoperative mean RSE +/- SD was -4.93 +/- 0.70 Dsph, six months after
      PRK, 100% of eyes had UCVA = 20/20. In the fourth group (> or = -7 Dsph)
      preoperative mean RSE +/- SD was -7.71 +/- 0.67 Dsph, six months after PRK, 57%
      of eyes had UCVA = 20/20, and 86% of eyes had UCVA > or = 20/40. There were no
      intraoperative complications while postoperative complications occurred in 2
      patients - in both cases in one eye (2%). In that cases, epithelial defects were
      detected. In the group of eyes that were treated by 6.5 mm OZ mean RSE +/- SD was
      -2.45 +/- 0.99 Dsph, the ablation depth per 1 Dsph was 17.54 +/- 5.58 microm and
      ablated volume of central 7 mm cornea by 1 Dsph was 0.43 +/- 0.18 mm3. In the
      group of eyes that were treated by 7 mm OZ mean RSE +/- SD was -3.32 +/- 2.26
      Dsph, the ablation depth per 1 Dsph was 23.73 +/- 6.91 microm and ablated volume
      of central 7 mm cornea by 1 Dsph was 0.61 +/- 0.31 mm3. CONCLUSION: PRK is
      effective and safe refractive surgical method for correcting myopia up to -8.75
      Dsph. OZ size is the main factor determining the depth of the excimer laser
      ablation of the corneal tissue volume consumed by 1 Dsph. Higher OZ value
      determines higher consumption of cornea tissue.

PMID- 23155606
TI  - [The quality of life in patients with diabetes mellitus type 2].
AB  - BACKGROUND/AIM: Through its vrious activities, World Health Organization (WHO)
      contributed to increasing the understanding of the concept of quality of life.
      People with diabetes have a lower quality of life than people without chronic
      illnesses. The aim of this study was to examine the differences in the quality of
      life, related to health, in patients with diabetes mellitus (DM) type 2 by age,
      gender and type of therapy. METHODS: We performed a cross-sectional study at the
      outpatient department of the Clinical Center in Novi Sad and the Health Center
      Ruma-General Practice. The group consisted of 90 patients with DM type 2, 41 men
      and 49 women. The age of respondents was from 40 to 80 years and they were
      classifed into four groups according to the ten-year age intervals. We applied
      WHO Quality of life questinnaire--BREF 100 composed of four domains: physical
      health, psychological health, social relationships and environment. The general
      questionnaire asks questions about socio-demographic data, duration of diabetes,
      the last value of blood glucose and glycosylated hemoglobin, training for self
      control and its implementation, informing patients about their disease, therapy
      and its impact on daily activities and the presence of comorbidity. In
      statistical analysis the following tests were used: Student's t-test, F-test,
      ANOVA (one way). RESULTS: The average duration of DM type 2 was 11.2 +/- 9.2
      years. Most of the patients (76%) were trained to self-control and 91% received
      enough information about their disease. Oral hypoglycemic preparations were used
      by 49%, insulin by 21%, and oral drugs and insulin by 29% patients while 1% were
      on a special regime of a diet therapy. Daily activities were performed without
      difficulties by over 29%, with some difficulties by 41% and 30% of patients who
      could not perform daily activities. The patients with DM type 2 had significantly
      lower scors in all 4 domains of quality of life (physical health, psychological
      health, social relations, environment). The biggest influence was on physical
      domains (51.31). Education level had an imact on physical and psychological
      domains. Comorbidity was found in 83% of the respondents. The most common were:
      arterial hypertension (63%), chronic cardiovascular disease (46%), neuropathy
      (23%), impaired vision 24%, elevated blood lipids (39%) and amputation of toes or
      feet (2.2%). The average value HbA1c in the group with comorbidity was 8.47% and
      in the group without comorbidity 6.46%. The subjects with comorbidity had low
      quality of life assessment in relation to the group without comorbidity: the
      domain of physical health (45.64 vs. 79.66), psychological health (50.3 vs.
      76.86), social relations (52.97 vs. 75.46) and environment (52.7 vs. 75.06).
      CONCLUSION: Diabetes mellitus type 2 has negative influence on the quality of
      life. It contributes to the presence of comorbidity. The occurrence of
      comorbidity was associated with higher glucosylated HbA1c values. There was no
      difference in the assessment of quality of life regarding gender, age, or the
      type of therapy used. The quality of life was assessed as low in patients with
      comorbidity. However, certain personality characteristics play a decisive role in
      self-evaluation.

PMID- 23155607
TI  - [The role of the posterior tibial slope on rupture of the anterior cruciate
      ligament].
AB  - BACKGROUND/AIM: Posterior tibial slope is one of the most citated factors wich
      cause rupture of the anterior cruciate ligament (ACL). The aim of this study was
      to determine the association of a greather posterior tibial slope on the lateral
      condyle, that is a lesser posterior tibial slope on the medial condyle, with ACL
      rupture. METHODS: The patients were divided into two groups. The study group
      included the patients with chronic instability of the knee besause of a previous
      rupture of ACL. The control group included the patients with knee lesion, but
      without ACL rupture. Posterior tibial slope measuring was performed by sagittal
      MR slices supported by lateral radiograph of the knee. We measured posterior
      tibial slope on lateral and medial condyles of the tibia. Using these values we
      calculated an average posterior tibial slope as well as the difference between
      slopes on lateral and medial condyles. RESULTS: Patients with ACL rupture have
      highly statistically significantly greather posterior tibial slope (p < 0.01) on
      lateral tibial condyle (7.1 degrees : 4.5 degrees) as well as statistically
      significantly lesser posterior tibial slope (p < 0.05) on medial tibial condyle
      (5.9 degrees : 6.6 degrees) than patients with intact ACL. CONCLUSION: Great
      posterior tibial slope on lateral tibial condyle associated with the small
      posterior tibial slope on the medial tibial condyle, that is a positive
      differentce between lateral and medial tibial condyles are factors wich may cause
      ACL rupture.

PMID- 23155608
TI  - Reliability and relationship of colposcopical, cytological and histopathological
      findings in the diagnostic process.
AB  - BACKGROUND/AIM: The question about the accuracy of cytology and colposcopy is
      more and more asked due to false positive and negative findings on the basis of
      which the decision on biopsy is made. The aim of this study was to examine
      reliability of biopsies based only on abnormal colposcopical findings, before
      receiving the results of Papanicolaou (PA) smear, by comparing findings of
      colposcopical, cytological and histopathological (HP) examinations as well as
      determining validity of these diagnostic methods. METHODS: The study involved all
      patients who had their regular colposcopical and cytological examinations in the
      outpatient department during a two-year period (2009-2010) in the Clinic for
      Gynecology and Obstetrics, Clinical Center of Serbia, Belgrade. The material for
      HP examination was obtained by colposcopically directed biopsy, due to abnormal
      colposcopical findings and without waiting for PA smear results. The data
      obtained by these methods were statistically analyzed and compared. Furthermore,
      validity of colposcopical and cytological examinations was assessed. Results. Out
      of 127 patients highly significantly more patients had more malignant cervical
      changes on colposcopical exam compared to HP (p = 0.000), and cytological exam (p
      = 0.000). Highly significantly more patients had more malignant cervical changes
      on PA smear than HP exam (p = 0.000), unless when findings were assessed in the
      widest sense of benign and malignant changes when there were no significant
      differences in these findings (p = 0.450). Sensitivity of colposcopy as a
      diagnostic method was 87.5%, specificity 24.14%, positive predictive value (+PV)
      was 34.65% and negative predictive value (-PV) 80.77%. Sensitivity of PA smear as
      a diagnostic method was 62.5%, specificity 87.36%, +PV was 69.44%, and -PV
      83.52%. CONCLUSION: Regarding the results of our study it is best to make a
      decision on treatment according to findings of all the three methods. Cytological
      analysis is more reliable than colposcopical examination. Therefore, it is
      advisable that following abnormal colposcopical findings, PA smear should always
      be taken and only after receiving the results further diagnostics can be planned
      (biopsy and HP). A final decision on the therapy has to be made based on HP
      findings which are the only method that can give the ultimate reliable diagnosis
      of cervical changes.

PMID- 23155609
TI  - Contemporary aspects of the diagnostics of alcoholic liver disease.

PMID- 23155610
TI  - Electronic health system--development and implementation into the health system
      of the republic of Serbia.

PMID- 23155611
TI  - [Plastic reorganisation of human motor cortex].

PMID- 23155612
TI  - Radionuclide treatment of metastatic disease in patients with differentiated
      thyroid carcinoma.

PMID- 23155613
TI  - Possibilities of thermovision application in sport and sport rehabilitation.
AB  - INTRODUCTION: Infrared thermography or thermovision is increasingly applicable in
      sport and sport rehabilitation. Thermic forms, thermic imprints, temperature and
      isotherm distribution, temperature gradient change are the terms that are more
      and more often met in sport medicine and medicine, in general. CASE REPORT: We
      presented two examples of thermovision application: in detection of muscle injury
      and changes of the feet exposed to low temperature. In the first example the
      thermovision method was used for analysing heat distribution in an athlete with
      back muscles injury. With a special original method of local cooling the place
      and degree of injury was precisely localized and determined, respectively,
      regardless high environmental temperature. In the second case the thermovision
      method was for the first time applied in a runner whose feet was exposed to low
      temperature. Significant hypothermia of the feet was detected by the method and
      appropriate treatment was performed. Thanks to this the athlete had no harmful
      consequences. CONCLUSION: Thermovision is fast and efficient in detecting
      different kind of injuries, so its increased use in the future can be expected.

PMID- 23155614
TI  - Heroin addict with gangrene of the extremities, rhabdomyolysis and severe
      hyperkalemia.
AB  - INTRODUCTION: Long-time consumption of narcotics leads to altered mental status
      of the addict. It is also connected to damages of different organic systems and
      it often leads to appearance of multiple organ failure. Excessive narcotics
      consumption or abuse in a long time period can lead to various consequences, such
      as atraumatic rhabdomyolysis, acute renal failure and electrolytic disorders.
      Rhabdomyolysis is characterized by injury of skeletal muscle with subsequent
      release of intracellular contents, such as myoglobin, potassium and creatine
      phosphokinase. In heroin addicts, rhabdomyolysis is a consequence of the
      development of a compartment syndrome due to immobilization of patients in the
      state of unconsciousness and prolonged compression of extremities, direct heroin
      toxicity or extremities ischemia caused by intraluminal occlusion of blood
      vessels after intraarterial injection of heroin. Severe hyperkalemia and the
      development of acute renal failure require urgent therapeutic measures, which
      imply the application of either conventional treatment or a form of dialysis.
      CASE REPORT: We presented a male patient, aged 50, hospitalized in the Emergency
      Center Kragujevac due to altered mental status (Glasgow Coma Score 11), partial
      respiratory insufficiency (pO2 7.5 kPa, pCO2 4.3 kPa, SpO2 89%), weakness of
      lower extremities and atypical electrocardiographic changes. Laboratory analyses,
      carried out immediately after the patient's admission to the Emergency Center,
      registered the following disturbances: high hyperkalemia level (K+ 9.9 m mol/L),
      increased levels of urea (30.1 mmol/L), creatinine (400 micromol/L), creatine
      phosphokinase--CK (12,0350 IU/L), CK-MB (2500 IU/L) and myoglobin (57000
      microg/L), with normal levels of troponin I (< 0.01 microg/L), as well as signs
      of anemia (Hgb 92 g/L, Er 3.61 x 10(12)/L), infection (C-reactive proteine 184
      microg/mL, Le 16.1 x 10(9)/L) and acidosis (base excess--18.4 mmol/L, pH 7.26.
      Initial examination of the patient revealed swelling and paleness of the right
      lower leg, signs of gangrene of the right foot and the 1st and the 4th toes of
      the left foot. The patient had normal values of arterial pressure (130/80 mmHg)
      and heart rate (64/min(-1)); roentgenographic lungs examination and computerized
      tomography (CT) brain examination did not reveal pathological changes in lung and
      brain parenchyma; toxicological analyses confirmed the presence of heroin in
      patient's organism. The patient was treated by intensive conventional treatment
      (infusion of crystalloid solutions, 8.4% solution of sodium bicarbonate, i.v.
      infusion of diuretics, calcium gluconate and short-acting insulin), and also by
      antibiotics and anticoagulants. Normalization of kalemia and fast regression of
      electrocardiographic changes were registered. The patient refused the suggested
      surgical treatment (fasciotomy, foot amputation). After stabilization of kidney
      function and improvement of his mental state, the patient agreed to undergo
      surgical procedure. Therefore, on the day 30 of hospitalization the above-knee
      amputation of the right leg was performed, and on the day 38 the transmetatarsal
      amputation of the left foot was carried out. After 46 days of hospital treatment,
      the patient was released and sent to home treatment. CONCLUSION: The routine
      laboratory diagnostics, which implies determining of the levels of potassium,
      urea, creatinine and CK in the serum of all hospitalized heroin addicts can
      contribute to timely detection of hyperkalemia and acute kidney weakness and
      undertaking of appropriate therapeutic measures.

PMID- 23155615
TI  - Elevation of troponin values in differential diagnosis of chest pain in view of
      pulmonary thromboembolism.
AB  - INTRODUCTION: Acute coronary syndrome, as unstable form of ischaemic heart
      disease, beside clinical presentation and electrocardiographic abnormalities, is
      characterized by increased value of troponin one of cardiospecific enzimes.
      Although troponin is a high specific and sensitive indicator of acute coronary
      syndrome, any heart muscle injury may induce its increasing, so there are some
      other diseases with the increased troponin value. CASE REPORT: We presented a
      female patient with chest pain, admitted because of suspicioun of acute coronary
      syndrome. Performed coronarography excluded ischemic heart disease. Considering
      symtomatology, electrocardiographic abnormalities, increased troponin and D-dimer
      values, as well as echocardiography finding we considered pulmonary embolism as a
      differential diagnosis, which was confirmed by pulmoangiography. CONCLUSION:
      Isolated increased troponin values are not enough for diagnosis of acute coronary
      syndrome.

PMID- 23155616
TI  - The Spanish flu--part II: the second and third wave.

PMID- 23155617
TI  - The Spanish flu (A coment on the article: Radusin M. The spanich flu--part I: the
      first wave. Vojnosanit Pregl 2012; 69(9): 812-7).

PMID- 23155618
TI  - [Mechanisms of cerebral protection from ischemia by tea constituents].
AB  - Epidemiological and clinical studies in recent years have shown that regular
      consumption of green or black tea significantly reduces the risk of
      cardiovascular diseases, including ischemic stroke. This review presents the
      clinical and experimental studies of the antiatherogenic, antiplatelet,
      antioxidant, antiinflammatory and other mechanisms of action of tea and
      substances in its composition. Effects of tea and its components, are described
      after long-term, and a short-term consumption. The role of catechins and specific
      amino acid L-theanine in the possible mechanisms of protection against
      cerebrovascular disease are discussed.

PMID- 23155619
TI  - [Phenomenon of heart ischemic postconditioning].
AB  - Authors of review analyzed papers on problem of heart ischemic postconditioning.
      In the review, it was demonstrated that postconditioning decreased an infarct
      size, prevented cardiomyocytes apoptosis, improved cardiac contractility in
      reperfusion period, augmented cardiac tolerance to arrhythmogenic impact
      ofreperfusion, prevented neutrophil invasion into the reperfused heart, abolished
      reperfusion endothelial dysfunction and suppressed reperfusion oxidative stress
      in myocardium.

PMID- 23155620
TI  - [Free radical modification of proteins in brain structure of Sprague-Dawley rats
      and some behaviour indicators after prenatal stress].
AB  - We studied the influence of late prenatal stress on free radical oxidation
      processes in Sprague-Dawley rats cortex, striatum, hippocampus, hypothalamus
      proteins. It was shown that after prenatal stress most changes were observed in
      hypothalamus and hippocampus. It was shown that in hypothalamus spontaneous
      oxidation level increased, but level of induced oxidation decreased, the opposite
      changes were found in hippocampus. Simultaneously minor changes of protein
      modification were observed in cortex and striatum. It was shown that prenatal
      stress changed both correlation of proteins free radical oxidation in studied
      structures and values of these data regarding to control. In test of "open field"
      motor activity in rats after prenatal stress decreased and time of freezing and
      grooming increased; opposite, in T-labyrinth motor activity and time of grooming
      in rats after prenatal stress increased, but time of freezing decreased.

PMID- 23155621
TI  - [Physiological effects induced by dermorphin synthetic analogue--opilong].
AB  - The effects of repeated opilong injections in a dose of 50 microg/kg/day on
      subsequent learning of Wistar rats have been studied. The substance caused
      significant anxiolytic and analgesic effects, as the majority of animals could be
      learned (90% against 40% in control group) despite of painful stimulus preceding
      to education. Opilong in a small dose displaced a relation of excitatory-inhibit
      processes to significant prevalence of excitation although the substance was
      already absent in an organism for a long time. Raised peripheral sensitivity in
      all rats, provoked by opilong, correlated with CNS hyper excitability, expressed
      in stressful, neurotic psychoemotional reactions and in the form of active
      avoidance. The biochemical blood analysis in opilong-induced rats demonstrated
      the attributes of prethrombosis in the form of fibrinolysis depression and
      hypercoagulation. A view is expressed, that the neuromediator brain systems can
      be the basic point of opilong action, that are responsible for the excitatory
      inhibit conditions of CNS functioning referred on maintenance of conditioned
      field stability.

PMID- 23155622
TI  - [Immunohistochemical study of CART-peptide in striato-nigral projections at
      dopamine loss].
AB  - The increase of CART-peptide optical density was found immunohistochemically in
      nucleus accumbens neurons and in their terminals in substantia nigra in Wistar
      rats after 28% reduction of dopaminergic neurons in a substantia nigra (in the
      model of lactacystin induced proteo some disfunction). At the same time after in
      vitro incubation of nigro-accumbal brain slice with AMPT (alpha-methyl
      paratirosine--dopamine inhibitor) for 4 h the reduction of tyrosine hydroxylase
      optical density (the enzyme limiting dopamine synthesis) in substantia nigr
      neurons was found and optical density of CART-peptide in nucleus accumbens and
      substantia nigra was also revealed. In both experiments data about activation of
      CARTergic neurons in stria to-nigral projections testifies on participation of
      CART-peptide in compensatory brain mechanisms at dopamine loss and its role as
      modulator of dopaminergic brain neurons functional activity.

PMID- 23155623
TI  - [The impact of early and late ischemic preconditioning on brain damage and degree
      of neurological deficiency in rats].
AB  - The present study was aimed to investigate neuroprotective effects of early and
      late ischemic preconditioning in the acute phase of ischemic brain damage in
      rats. It was found that a single five-minute ischemic episode of early ischemic
      preconditioning did not lead to significant neuroprotective effects in comparison
      with control group, while three five-minute ischemic episode early ischemic
      preconditioning accompanied by a significant increase in neurological deficit and
      growing damage rate in CA1 hippocampus neurons. In contrast, later ischemic
      preconditioning in form of single five-minute episode 24 hours before ischemia
      modeling, provided a significant neuroprotective effect, manifesting reduced
      neurological deficit and maintaining viability of CA1 hippocampus neurons.

PMID- 23155624
TI  - [Liver phospholipids composition and activity of glutathione redox-system in rats
      on prolonged high-fat diet].
AB  - We studied liver phospholipid composition and activity of the glutathione redox
      system in rats on prolonged for 180 days high-fat diet. The adaptive response was
      formed from day 30 to day 90 of high-fat load and was associated with increased
      relative content of phosphatidylseryne and phosphatidylethanolamine homeostasis.
      Constant antioxidant activity of glutathione redox-system for 30 days period of
      high-fat load was achieved by stable glutathioneperoxidase activity, on 90th day-
      level of glutathione reductase increased. The detected fluctuations in
      phospholipid composition and activity of glutathione redox-system in liver tissue
      on 30-90th days of the experiment indicated the formation of a compensatory
      response to maintain cell integrity. On 180th day of high-fat load due to
      exhaustion of compensatory mechanisms in the glutathione antioxidant defense and
      intensification of lipid peroxidation the lipid matrix of cytomembrane underwent
      profound restructuring associated with decreased levels of phosphatidylinositol,
      phosphatidylethanolamine, increased proportion of apoptotic phospholipids
      (phosphatidylserine, sphingomyelin). Such phospholipids composition on the
      background of glutathione redox-system inhibition can determine apoptosis,
      necrosis and liver fibrogenesis. These results extend the knowledge about
      mechanisms of liver adaptation and disadaptation to nutritional stress.

PMID- 23155625
TI  - [Effect of alpha2-adrenergic receptor antagonist yohimbine on thermoregulatory
      responses to cooling].
AB  - Ionoforetic yohimbine application to skin has a modulating effect on the
      thermoregulatory parameters. In thermoneutral conditions, yohimbine increases
      heat production and heat dissipation. At subsequent cooling, yohimbine
      facilitates the initiation of vascular and metabolic response by reducing the
      temperature threshold of both nonshivering and shivering thermogenesis. Under the
      influence of yohimbine the maximum value of both vascular and metabolic response
      increases. In strengthening the metabolic response the skeletal muscles shivering
      significantly contributes. In contrast to yohimbine, the norepinephrine
      thermogenic effect occurs by strengthening nonshivering thermogenesis. Features
      of the yohimbine influence on thermoregulatory parameters due to the dual
      localization and function of the alpha2-adrenergic receptors.

PMID- 23155626
TI  - [Opioid peptides effect on lipid peroxidation in long-term stress].
AB  - It was shown in rats, that injection of opioid peptides (dynorphin A (1-13),
      DSLET and DAGO) decreased the stress-induced activation of lipid peroxidation in
      liver tissue and plasma. Dynorphin A (1-13) manifested the most expressed
      antioxidant effect in liver tissue. It not only decreased lipid peroxidation
      metabolites concentration, but also increased superoxiddismutase and catalase
      activity. Other peptides did not interfere enzyme activity. The use of DSLET or
      DAGO increased the superoxiddismutase plasma activity. Dynorphin A (1-13)
      injection increased catalase activity, but not superoxiddismutase. These effects
      could be explained by peculiarities of opioid receptors spread in liver tissue
      and stress-limiting action of peptides in entire organism.

PMID- 23155627
TI  - [Exenatide stimulated solute-free water excretion by human kidney].
AB  - Exenatide effect was studied in 55 human including 38 patients with type 2
      diabetes mellitus without signs of diabetic nephropathy and primary renal
      diseases. Preliminary study with water load in volume from 0.5 to 1% b.w. showed
      that water load equal to 0.7% b.w. caused significant increase in urine
      excretion. The rise of diuresis after 10 microg Byetta (exenatide) injection and
      simultaneous water load of 0.7% of b.w. depended on increase in solute-free water
      clearance. Thus, exenatide (mimetic of GLP-1) action let us to consider its
      possible role as component of osmoregulation system in human. This peptide
      provides high efficiency of renal function in osmotic homeostasis.

PMID- 23155628
TI  - [M1 and M2 macrophage phenotypes functional activity as essential components in
      innate immune response assessment].
AB  - Macrophage capacity to phagocytosis and migration activity are crucial components
      in innate immune response assessment. Differences in functional responses of two
      macrophage phenotypes were detected. Phagocytic activity of proinflammatory
      alveolar M1 phenotype in relation to S. aureus is more expressed than of
      antinflammatory M2 phenotype. Comparative analysis of migration activity showed
      alternative dependence of migration index on the type of used chemoattractant.

PMID- 23155629
TI  - [Terminology of umbilical access surgery: a new Babel?].

PMID- 23155630
TI  - [Cold-knife retrograde endoscopic endopyelotomy (Cutting-Balloon) in children
      with ureteropelvic junction obstruction: early results].
AB  - BACKGROUND: To present our early experience in the use of Cutting-Balloon for the
      treatment of resistant or relapsed ureteropelvic junction obstruction (UPJO)
      after a prior endourological retrograde high-pressure balloon dilatation (RHPBD).
      MATERIALS AND METHODS: Patients with progressive hydronephrosis and impaired
      drainage of the renal pelvis on a diuretic renal scan were treated with RHPBD. In
      those patients with resistant UPJO (waist persistence after dilatation) or
      relapsed UPJO, we consider using a Cutting-Balloon as an alternative to our
      current protocol (second RHPBD or open surgery). A JJ stent was placed following
      the procedure, and removed at 4-6 weeks. Outcomes were evaluated 3 and 6 months
      after stent removal, and every 6 months thereafter, repeating renal
      ultrasonography and diuretic renal scan. RESULTS: Between 2008 and 2010 we
      treated with Cutting-balloon 5 patients (4 male, 1 woman) with UPJO (left side: 3
      cases, right side: 1 case, bilateral: 1 case) with a mean age of 3 months (range,
      10 days to 7 months). Four cases had resistant UPJO and 1 case relapsed UPJO.
      After the procedure, and during the follow-up period of 12 months (range, 9-18
      months), no further treatment was necessary. Four patients had improvement of
      hydronephrosis, with normal relative renal function (RRF). One patient (RRF 18%
      before treatment) did not improve. No periprocedural complications occurred.
      CONCLUSIONS: Cutting-balloon retrograde endopyelotomy seems to be a treatment
      with encouraging early results for resistant and relapsed UPJO, after a prior
      RHPBD. We believe that further clinical evaluation is needed to confirm these
      findings.

PMID- 23155631
TI  - [Ovarian cryopreservation in girls with cancer: new challenges].
AB  - BACKGROUND: Ovarian cortex cryopreservation (OCC) for future autotransplant
      represents a treatment alternative for those paediatric cancer survivors affected
      of ovarian failure and fertility disorders. METHODS: Patients with high
      gonadotoxic risk are included in the Oncology Paediatric Fertility Preservation
      Programme: those receiving pelvic radiotherapy, bone marrow transplantation, high
      doses of cranial radiotherapy or alquilating agents, or those with bilateral
      ovarian pathology. Prior to the oncological treatment, the ovarian tissue is
      harvested laparoscopically. At the same time, other invasive procedures are done.
      Once malignancy is ruled out of the specimen and the presence of primordial
      follicles is confirmed, the multidisciplinary team of oncologist, paediatric
      surgeon and fertility specialist coordinate the processing and delivery of the
      ovarian cortex to the Comunidad Valenciana Tissue Bank. RESULTS: From July 2008
      to May 2010 eight patients have been included in the programme, aged between 8-18
      years old and with diagnosis of: Hodgkin's lymphoma (n= 2), Acute Myeloblastic
      and Lymphoblastic leukaemia (n= 2), pelvic Ewing's sarcoma, bilateral ovarian
      Teratoma and Meduloblastoma. Five patients underwent non gonadotoxic chemotherapy
      before OCC. Six additional procedures were done using the same anaesthetic event.
      Partial oophorectomy was performed in half the cases, total oophorectomy in the
      rest of them, and an ovarian pexia was once associated. All taken samples were
      found to be valid. CONCLUSIONS: OCC of selected patients was performed safely,
      with neither postoperative complications nor delay of the oncological treatment.
      Therefore, the first national experience in this procedure has been
      satisfactorily achieved.

PMID- 23155632
TI  - [Preliminary results in the correction of the pectus excavatum with the Acastello
      modified Welch technique].
AB  - BACKGROUND: Congenital malformations of the chest wall are a heterogeneous group
      of diseases affecting the costal cartilage, ribs, sternum, scapula and clavicle.
      The pectus excavatum is characterized by a posterior depression of the sternum.
      Acastello-Welch technique consists in a partial resection of the costal
      cartilages adding some bars or plates unilaterally fixed to the sternum in each
      hemithorax. MATERIALS AND METHODS: From October 2008 to March 2011 we evaluated
      108 patients with congenital malformations of the chest wall. Forty-seven
      patients (44%) had a pectus excavatum and 12 were treated with Acastello-Welch
      technique. RESULTS: There were no intraoperative complications. After a mean
      follow up of 27 months, correction of the deformity was very satisfactory both
      objective and subjective for patients. CONCLUSIONS: The Welch thoracoplasty
      modified by Acastello is a good option for the correction of the pectus excavatum
      associating little morbidity and good esthetic outcomes.

PMID- 23155633
TI  - [Subcutaneously inserted central intravascular devices in the pediatric oncology
      patient: can we minimize their infection].
AB  - Long-term indwelling central venous access devices are frequently used in
      pediatric patients. Their main complication is infection, that can even mean
      their removal. We try to identify the risk factors really involved in this
      complication and in their removal. We have made a retrospective review of 120
      oncologic pediatric patients who received a central venous device between 2003
      and 2009. We searched for epidemiologic, clinic, microbiologic and surgical risk
      factors. We made a comparative data analysis among: GROUP A, children who
      suffered device infection, GROUP B the others. Group A was divided into early
      infection (first month after implantation)/late infection, removed/not removed.
      Data were analized with statistical program SPSS. 29 suffered from leukemia, 19
      from lymphoma and the main part, 72, from solid tumour. 31% experienced infection
      (GROUP A), being early in the 36% of them. 16% had to be withdrawn. Data analysis
      revealed statistical association with the age (p=0.015) and with the reception of
      chemiotherapic treatment the week before the surgical insertion. The rest of the
      studied factors did not revealed a real association, but could be guess a
      relationship among infection and leukemia, subclavian catheters, those patients
      whose deviced was introduced using a guide over a previous catheter and also
      transplanted. Related to early infection the only associateon founded was with
      the subclavian access (p=0.018). In conclusion, in our serie long-term central
      venous access infection was more frequent in the younger patients and also in
      those who had received chemotherapy the week before the catheter implantation.
      The tendency towards infection in leukemia, transplanted and subclavian carriers
      has to be studied in a prospective way with a larger number of oncologic
      children.

PMID- 23155634
TI  - [Spanish pediatric research in MEDLINE].
AB  - The objective of this work was to elaborate and apply search filters to retrieve
      the Spanish scientific output (SO) in pediatrics. A bibliographic search was
      carried out in MEDLINE. The search was based on the construction and application
      of a Spanish geographic filter, elaborated according to a previous model, and a
      thematic one to retrieve records in the pediatric area. The following was
      determined: frequency of the records, place of publication, language, journal,
      number of authors and year of publication; to observe the dynamics of the SO, a
      bibliographic study was carried out over a period of ten years. By applying the
      geographic filter, 277,949 records were retrieved; 620 were retrieved in the
      pediatric Spanish area. Of these, 262 (42.26%) were published between 2000-2009.
      Most of records were signed by one author. In Spain, the records were published
      in 42 journals and abroad in 79 journals. A search filter able to retrieve the
      pediatric Spanish SO was created, that supposed 1.22% of the total records in the
      pediatric field encompassed by MEDLINE. Approximately 80% of these articles were
      published in Spain.

PMID- 23155635
TI  - [Is experimental surgery necessary or essential in the training program of a
      pediatric surgeon?].
AB  - Many surgical procedures performed in pediatric surgery have a slow learning
      curve, the volume of patients and the existence of complex diseases that require
      extensive training and surgical skill, have taken our service to create a global
      training program of experimental surgery. This program based on the simulation
      and training invasive procedures in real anatomical models, aims to educate our
      residents in a global and efficiently way in order to obtain an improvement of
      technical training, and increased patient safety result of experience and
      expertise wined in the experimental animal. This paper presents the main
      features, objectives and results obtained with this training program and seeks to
      promote the incorporation of simulation programs in live animal as an essential
      part of the training of pediatric surgery resident.

PMID- 23155636
TI  - [Robotics in pediatric surgery].
AB  - Despite the extensive use of robotics in the adult population, the use of
      robotics in pediatrics has not been well accepted. There is still a lack of
      awareness from pediatric surgeons on how to use the robotic equipment, its
      advantages and indications. Benefit is still controversial. Dexterity and better
      visualization of the surgical field are one of the strong values. Conversely,
      cost and a lack of small instruments prevent the use of robotics in the smaller
      patients. The aim of this manuscript is to present the controversies about the
      use of robotics in pediatric surgery.

PMID- 23155637
TI  - [Initial experience in single site laparoscopic surgery in a pediatric hospital
      of Bogota].
AB  - BACKGROUND: Minimally invasive surgery is the current accepted approach for
      abdominal surgery. However, less invasive techniques such as single incision
      laparoscopic surgery (SILS) are being used more frequently and we believe it will
      become the standard choice for abdominal surgery. This report describes our
      initial experience with Single Port Incision Surgery (SILS). METHODS: We reviewed
      all the patients who underwent SILS in our hospital between November 2009 and
      July 2011. We used a surgical glove attached to a wound retractor to yield a
      multi-port hybrid. RESULTS: We present 80 patients with a mean age of 8.6 years
      and mean weight of 32,1 kg. The youngest patient was 8 days old and the smallest
      patient weighed 2.5 kg. The average duration of surgery was 48.2 minutes. The
      average length of stay was 48.7 hours. Different procedures were performed:
      appendectomies for early appendicitis (55%), hepatic biopsies (15%),
      appendectomies for perforated appendicitis (7.5%), and the following isolated
      cases: cholecystectomy, Meckel's diverticulum resection, oophorectomy, salpingo
      oophorectomy, ovarian cystectomy, bowel biopsy, and a resection of an accessory
      spleen torsion. SILS was successfully completed in 78 cases, and 2 cases were
      converted to standard laparoscopy and none to open surgery. There were no
      intraoperative surgical complications. Postoperative complications presented in 5
      cases: a superficial incisional site infection, two residual abdominal abscesses,
      one bowel obstruction and one evisceration. The last two cases subsequently
      resulted in reoperation and occurred early in our learning curve. CONCLUSIONS:
      SILS is a reproducible and viable technique that may be used successfully in
      pediatric surgery. It may be used safely in different procedures and age groups,
      even in neonates. Time of surgery decreased with our learning curve.
      Additionally, excellent cosmetic results were obtained as evidenced by
      imperceptible umbilical scarring.

PMID- 23155638
TI  - [Our experience in retroperitoneoscopic total or partial nephrectomies].
AB  - The retroperitoneal laparoscopic approach is displacing open surgery and
      transperitoneal approach for several benign renal conditions. In the past 6 years
      we have performed 20 procedures, 10 with lateral position and 10 with posterior
      prone one: 13 total nephrectomies and 7 heminephrectomies in children aged 4,1
      years on average. Mean operative time was 200 minutes in partial procedures and
      278 in the total ones. Oral feeding was restored to 11,4 hours and average
      hospital postoperative stay was 1,58 days in total nephrectomies and 2,18 in
      heminephrectomies. There was no intraoperative bleeding. Complications were two
      urine leaks, two infections due to residual ureteral stumps and a case of
      transient hematuria. There were no significant differences between posterior and
      lateral approaches as to hospital stay, time of onset of oral feeding or
      complications, although the average operative time was shorter in the posterior
      approach (mean 170 min, SD 17,3) than in the lateral one (mean 216 min, SD 41)
      (P=0,024) in total nephrectomies. Retroperitoneoscopy allows a safe access to the
      kidney and avoids morbidity associated with the transperitoneal access. The
      posterior approach provides better vascular control, maintains the peritoneum far
      and allows the procedure with fewer ports, maximizing work space.

PMID- 23155639
TI  - [Laparoscopic nephroureterectomy in Wilms tumor].
AB  - INTRODUCTION: Minimally invasive surgery (CMI) for the treatment of malignant
      tumors in children begins to have a role for selected cases and reaches similar
      results than open surgery. We show our first two cases of Wilms tumor treated by
      laparoscopy describing patients and technique. MATERIAL AND METHODS: Three-year
      old girl with macroscopic hematuria is diagnosed of 8 cm mass in the left kidney
      suggesting Wilms tumor. After 4 weeks of chemotherapy she went under laparoscopic
      nephroureterectomy. The histological result was Wilms tumor. Chemotherapy was
      completed seven more months. Five-year-old patient with abdominal pain is
      diagnosed of renal right mass suggesting Wilms tumor. After 4 weeks of
      chemotherapy the laparoscopic nephroureterectomy was performed. The histological
      result was Wilms tumor. Treatment was completes with postoperatory chemotherapy.
      RESULTS: After 1 year follow-up both patients have clinical and radiological
      absence of disease. CONCLUSION: The CMI in selected cases of Wilms tumor fulfills
      successfully the aims of the surgical treatment.

PMID- 23155640
TI  - [Heterotaxy-polysplenia, approach to the esophageal hiatus for Nissen technique].
AB  - INTRODUCTION: Heterotaxy is a failure in embryonic development to achieve left
      right symmetry. OBJECTIVE: To report a case of heterotaxy and show a surgical
      approach for fundoplication. MATERIAL AND METHODS: A girl with heterotaxy
      polysplenia syndrome with gastroesophageal reflux and recurrent abdominal pain.
      It was decided to perform laparoscopic antireflux treatment with Nissen
      fundoplication with approach by the right side of the diaphragmatic hiatus and
      pillars. CONCLUSIONS: Surgery is being discussed in these syndromes, indicating
      only in cases of recurrent abdominal pain, subocclusive lesions or when diagnosis
      of gastroesophageal reflux is done. The dilemma is between laparoscopic or
      classical laparotomy. The main difficulty of the laparoscopic approach is the
      enlarged liver and stomach placement right despite the esophageal hiatus is
      normally on the left side.

PMID- 23155641
TI  - [Training of pediatric surgeons in the dawn of the XXI century].

PMID- 23155642
TI  - [Traumatic diaphragmatic hernia: a vital need for an early diagnosis].
AB  - INTRODUCTION: Traumatic diaphragmatic hernia (HDT) is exceptional in children.
      Its diagnosis is usually delayed for appearing in the context of severe
      polytrauma. The aim is to analyze our series in relation to the severity scores.
      PATIENTS AND METHODS: Five patients with HDT are presented. Age, biomechanics,
      clinical, ISS (injury severity score), ITP (pediatric trauma index), GCS (Glasgow
      coma scale), RTS (Revised Trauma Score) and treatment were studied. The
      probability of survival (Ps) was calculated with the TRISS method, Ps = 1/(1 +
      eb), b = b0 + bl (RTS) + b2 (ISS) + B3 (age). RESULTS: There were two males and
      three females, mean age was six years old (range = 3-10). Traffic accident was
      the mechanism of the thoracoabdominal trauma in 80% and one was crushed by garage
      door. The affected side was right in two cases and left in three. Mean ISS was 41
      (range = 32-57), ITP 6 (range = 2-9) and RTS 6.1 (range = 5.1 to 6.9). The main
      symptom was respiratory. Plain chest radiography was diagnostic in three
      patients, one by CT scann, and another was a finding at laparotomy. Two had liver
      herniation, one had tension gastrothorax and two had gastric perforations. All
      patients underwent surgery through the abdomen. Estimated survival by the TRISS
      method was respectively 86.6%, 78.2%, 57.2%, 84.7% and 57.1%, while the actual
      was 100%. One has a severe disability. DISCUSSION: To study the biomechanics and
      semiology is essential in the early diagnosis of TDH in pediatric polytrauma and
      suspect it is mandatory prior to realize percutaneous chest procedures. The TRISS
      method has a great importance to assess the adult polytrauma, but specific scores
      are needed for children.

PMID- 23155643
TI  - [Estimation of the risk of upper digestive tract bleeding in patients with portal
      cavernomatosis].
AB  - PURPOSE: The aim of this study is to find out the risk of upper gastrointestinal
      bleeding (UGB) after the diagnosis of portal cavernoma in children, and to
      investigate several potential risk factors. MATERIAL AND METHODS: We analyzed
      retrospectively 13 cases of portal cavernoma and estimated the risk of UGB with
      the Kaplan-Meier survival analysis. We calculated the incidence rate of the
      sample and the number of haemorrhages per year for each patient individually.
      From the moment of the diagnosis various parameters were recorded: age,
      platelets, leukocytes, hemoblobin, hematocrit, prothrombin time and number of
      bleedings. The relation between these parameters and the risk of bleeding was
      assessed with the Cox analysis. RESULTS: The patients were followed for a median
      period of 7.1 years. 10 patients (77%) presented at least 1 episode of UGB after
      the diagnosis. The median survival time until the first haemorrhage was 314 days.
      After the diagnosis the incidence rate of the sample was 0.43 episodes of upper
      gastrointestinal bleeding per person-year. The number of individual bleedings per
      person had a range of 0-2.2 episodes per year. CONCLUSIONS: There is very few
      data about the risk of bleeding in children with portal cavernoma. In our sample,
      we found out an incidence rate of 0.43 and a median survival time of 314 days
      until the first episode of bleeding after the diagnosis, but we were not able to
      find a statistically significant association between the studied variables and
      the risk of bleeding.

PMID- 23155644
TI  - [Generation of a substitute for human oral mucosa and verification of its
      viability by tissue-engineering].
AB  - Reconstruction of large oral mucosa defects is often challenging, since the
      shortage of healthy oral mucosa to replace the excised tissues. This way, tissue
      ingineering techniques may provide a source of autologous tissues available for
      transplant in these patients. In this work, we have developed a new model for
      artificial oral mucosa generated by tissue engineering using a fibrin-agarosa
      scaffold. For that purpose, we have generated primary cultures of human oral
      mucosa fibroblasts and keratinocytes from small biopsies of normal mucosa oral
      using enzymatic treatments. Then, we have determined the viability of cultured
      cells by electron probe quantitative X-ray microanalysis, and we have
      demonstrated that most of the cells in the primary cultures were alive and hd
      high K/Na ratios. Once cell viability was determined, we used cultured
      fibroblasts and keratinocytes to develop an artificial oral mucosa construct by
      using a fibrin-agarosa extracellular matrix and a sequential culture technique
      using porous culture inserts. Histological analysis of the artificial tissues
      showed high similarities with normal oral mucosa controls. The epithelium of the
      oral substitutes had several layers, with desmosomes and apical microvilli and
      microplicae. Both the controls and de oral mucosa substitutes showed high
      suprabasal expression of cytokeratin 13 and low expression of cytokeratin 10. All
      these results suggest that our model of oral mucosa using fibrin-agarose
      scaffolds show several similarities with native human oral mucosa.

PMID- 23155645
TI  - [Comparative analysis between the Seldinger technique vs. open dissection in the
      implantation of intravenous reservoirs].
AB  - OBJECTIVE: To analyze advantages and disadvantages between Seldinger's technique
      (ST) and surgical dissection (SD) on intravenous port-a-caths comparing surgical
      parameters as time and complications. MATERIAL AND METHOD: An analytic
      retrospective study involving historic cohorts was realized, comparing our
      surgical experience on port-a-cath implantation with Seldinger technique or
      surgical dissection. Statistical analysis was made reflecting clinical and
      surgical parameters, such as surgical time length and intra/postoperative
      complications. RESULTS: 193 Port-a-caths were analyzed (119 SD, 74 ST), mainly
      placed for chemotherapy treatment (83.41%). Surgical time length expended at
      single procedures was 72.85 +/- 29.35 minutes for SD and 62.83 +/- 20.08 minutes
      for ST (p < 0.05). There were none operator-dependent differences. Statistically
      significant differences were not found between the two cohort's populations,
      neither at complications percentages. Greater-sized port-a-caths presented a
      higher average of skin necrosis (p > 0.05) however, lower-sized port-a-caths
      showed a higher average of infection (16% upon 7.7% p > 0.05). Both ST (51.67 vs.
      98.14 min) and SD (78.56 vs. 123.61 min) showed lower surgical time length at
      left venous accesses (d = 171 vs. i = 19). Average in days for the extraction of
      port-a-caths with regard to complications was 121 days. CONCLUSION: Seldinger
      technique reduced the definitive lost of surgical dissected venous accesses,
      being possible further utilization of the same vein for subsequent port-a-caths.
      Seldinger technique reduces surgical time length without increasing
      complication's rate. Left venous access does not imply higher surgical time
      length. Complications may be related with port-a-cath's size.

PMID- 23155646
TI  - [Very severe hepatic trauma in childhood. The report of two cases with minimally
      invasive treatment].
AB  - Liver trauma in children is a pathology that has an increasing incidence mainly
      due to the implications of growing children in hazardous games and sports
      adventure, and the frequent car accidents. There has been a shift of management
      in haemodynamically stable patients towards non-operative management. This allows
      in most cases a patient's complete recovery without surgical aggression,
      preventing further damage derived from the handling of the injured liver.
      Herewith we report two cases of a 6 and 4 year old boys who suffered a very
      severe traumatic rupture of the liver. They were operated through minimally
      invasive surgical procedures, achieving complete resolution of the serious
      damages.

PMID- 23155647
TI  - [Evaluation of urodynamics and continence in bladder augmentations with
      sigmoids].
AB  - AIM: To evaluate our experience in sigmoid augmentation to manage renal upper
      tract dilatation and urinary incontinence. MATERIAL AND METHODS: Retrospective
      descriptive study of the augmentation cystoplasties with sigmoid patch. We
      analyze clinical, urodinamic and surgical parameters. RESULTS: We have make 30
      cistoplasties with a mean age of 10.24 years (3-15 years) with a mean follow up
      of 8 years (9 months-15 years). The main diagnosis was neurogenic bladder (63,3%)
      being the main indication for the augmentation the progressive dilatation of the
      renal upper tract (43,3%). We associate to the procedure the collocation of an
      artificial sphinter (30%), Mitrofanoff or ureteral reimplantation. There was no
      major complication. In the urodinamics, the bladders had low capacity, high
      pression and low compliance. After surgery, urodinamic parameters improve. During
      follow up, continence improve with more intermittent clean catheterism (median
      4/day). Vesical lithiasis was more common late complication with nor acute
      abdominal surgical illness nor malignancy; 2 patients finished in renal
      transplantation. Evolution was positive in 66%, and negative in 18,5%.
      CONCLUSIONS: Sigmoid augmentation cystoplasty is a good technique, that allows
      urodinamic and continence improvement. The conscience in the importance of
      intermittent catheterisms reduces the incidence of complications.

PMID- 23155648
TI  - [Surgical risk scale in pediatric surgery].
AB  - INTRODUCTION: The need to measure the level of surgical risk arises from its
      direct relationship with the development of postoperative complications and the
      use of hospital resources. The construction of a surgical risk scale (ERQ) for
      pediatric surgery should be based on a common language, by using a small number
      of easy to collect and reproduce variables. The objectives of this study were to
      construct an ERQ for pediatric patients and to analyze the surgical performance.
      MATERIALS AND METHODS: We retrospectively analyzed 105 primary surgical
      procedures under general anesthesia performed by liver transplantation service at
      Hospital Garrahan, between 29/6/08 and 25/3/10. Newborn patients were not
      considered. The ERQ was built by adding patient risk factors (PRL): weight (< o >
      10 kg), co-morbidities (coagulopathy-obesity-diabetes) and life support; and the
      magnitude level of the surgical procedure (SPL): surgical time and requirement of
      blood transfusions. The surgical performance was considered as a relation between
      the level of surgical risk and the post-operative results, measured with the
      classification of surgical complications proposed by Clavien et al (STROC). The
      main end point of the study was the STROC > or = 3 (severe complications). The
      ERQ predictive power for serious complications was compared with the anaesthetic
      risk (ASA). Descriptive and analytical statistics took place. The predictive
      value for complications was calculated by means of a ROC curve. The estimation of
      the risk was calculated by relative risk. RESULTS: The ERQ was constituted on a
      continuum of 6 risk levels (2 to 7). The ROC's curve predictive power to
      determine the development of severe post-operative complications (STROC > or = 3)
      was 0.87 (CI 0,80-0,94) for the ERQ and 0.81 (CI 0,73-0,89) for the ASA. Level of
      > or = 5 of ERQ was the cut-off point that better predicted the development of
      STROC > or = 3. CONCLUSION: The ERQ is an easy tool, useful to quantify and
      compare surgical risks and results. It showed a high predictive power of
      postoperative complications.

PMID- 23155649
TI  - [Botulinic toxin type A in the treatment of children with neurogenic bladder].
AB  - INTRODUCTION. Botulinum toxin A (BoNTA) is an alternative in children with
      neurogenic bladder refractory to anticholinergics. OBJECTIVE. To evaluate the
      initial effects of BoNTA in neurogenic bladders. PATIENTS AND METHODS 12 patients
      (9 myelomeningoceles, 1 tethered cord, 1 medullary astrocytoma, 1 Ewing's
      sarcoma) were studied. The pretreatment evaluation included: voiding diary,
      incontinence score, renovesical ultrasound, cystourethrography and urodynamic
      parameters. Patients received 300 UI of BoNTA via detrusor injections. They were
      re-evaluated at months 1, 3 and 6. After the third control, if improvement was
      confirmed, patients were injected again. Otherwise, surgery was indicated.
      RESULTS: After the initial injection, 50% of patients achieved complete
      continence and 20% remained with minimal leaks. The mean maximum bladder capacity
      increased from 264 +/- 117 ml to 324 +/- 170 ml (P = 0.322). The mean detrusor
      pressure decreased from 46 +/- 17 cm H2O to 42 +/- 14 cm H2O (P=0.596). The mean
      bladder compliance increased from 7.6 +/- 5.9 ml/cm H2O to 10.4 +/- 6.4 ml/cm H2O
      (P = 0.290). The reflex voiding contractions disappeared in 2 patients; 8
      presented trabeculae. Ten patients were reinjected and two underwent surgery.
      CONCLUSION: 70% urinary continence was achieved after the initial injection. No
      significant urodynamic changes were observed. A longer follow-up with subsequent
      injections is needed.

PMID- 23155650
TI  - [Correction of the complicated pectus excavatum with extracorporeal circulation
      (ECC) support].
AB  - INTRODUCTION: The most serious complication in surgery of the pectus excavatum is
      the possible cardiac perforation. After its resolution, it is very likely that
      the relapse of the excavatum will be more severe due to the intense retrosternal
      fibrosis generated, involving cardiac structures and fixing them to the sternum.
      Reintervention requires modifications of the usual techniques and special
      monitoring due to the increased risk of cardiac and large vessel lesions. We
      present the case of 2 patients with severe pectus excavatum with a previous
      attempt for correction with cardiac perforation. CLINICAL CASES: Case 1. A 16
      year old male with Haller index 9.9, diagnosed of Ehlers-Danlos syndrome and
      operated on in neonatal period of cardiac disease, with previous attempt for
      correction using the Ravitch technique that relapsed and cardiac perforation
      during it. Case 2. An 11 year old girl, with background of diaphragmatic hernia
      and cardiac perforation on introducing the Nuss bar at 5 years of age, with
      Haller index 5.5. Both were operated on under ECC with the collaboration of the
      Cardiac Surgery Service and cardiac adherences were released after median
      sternotomy. After it, the Nuss bar was introduced and then sternal closure was
      performed with reinforced steel wires with titanium plates in the anterior and
      posterior part. DISCUSSION: The backgrounds of the cardiac approach complicate
      the intervention for the correction of the pectus excavatum, with a high risk of
      cardiac trauma. Counting on the support of the cardiac surgery and the ECC, we
      achieve an adequate control and prediction of the complications

PMID- 23155651
TI  - [Minimally invasive surgery in pediatric patients with ventriculo-peritoneal
      shunts].
AB  - The use of laparoscopy in patients with ventriculo-peritoneal shunts has been
      controversial. There is concern about the risk malfunction or infection of the
      shunt as well as about the possibility of adhesions that could make the surgical
      procedures too difficult to be undertaken by minimally invasive surgery. We
      present our results in pediatric patients with ventriculoperitoneal shunts that
      have undergone laparoscopic procedures in our department. We have performed 16
      surgical procedures. The most frequent indication was fundoplication. During
      surgery there were no complications or intracranial hypertension episodes. Two of
      the procedures were considered by the surgeons more difficult and longer than
      usual. None of them required conversion to open technique. One shunt had to be
      replaced after surgery because of infection. According to our experience
      minimally invasive surgery is feasible and safe in pediatric patients with
      ventriculo-peritoneal shunts.

PMID- 23155652
TI  - [Phimosis: dorsal slit or circumcision?].
AB  - INTRODUCTION: Phimosis is perhaps one of the most frequent consultation on
      pediatric surgery clinics throught the world. The aim of this study is to compare
      the two procedures more frequently performed in our hospital: dorsal slit and
      circumcision. PATIENTS Y METHODS: Retrospective study of 1698 patients who were
      admitted for elective surgical treatment of phimosis between 2003 and 2009. We
      analyzed age, surgical and anesthethic times, surgical technique and
      complications. We also did transversal descriptive study through telephonic
      survey on parents and patients older than 16 years old. RESULTS: There was 76.6%
      of dorsal slit (n = 1300) and 23.4% (n= 398) of circumcisions. Mean age was 7.15
      years y mean time of follow up was 42.3 months. Surgical time was significantly
      higher in circumcision (p < 0.0001). There were 3% (n = 51) of reoperations, no
      differences between groups. We didn't find differences in postoperative stenosis,
      but bleeding was more frequent in circumcision group (1.7%; p = 0.03). There were
      no differences on parental appreciation of postoperative pain, or functional and
      esthetic satisfaction between groups. CONCLUSIONS: We didn't find differences on
      subjective satisfaction between groups. Even if there are differences n
      postoperative bleeding, global incidence is very low. In our experience both
      techniques are valid and safe, so surgeon and parents must jointly make the
      decision.

PMID- 23155653
TI  - [Venous embolization--treatment of choice in varicoceles].
AB  - Varicocele consists of the varicose expansion of the spermatic vein. It's more
      frequently in the left side (10:1) as consequence of an evil functioning or
      absence of the valves of the spermatic left vein. Between March 1999 and December
      2009 there have been gathered a total of 37 cases diagnosed of varicocele in the
      pediatric population of our center. After a local anesthetic we created a femoral
      aproach. We advance into the left renal vein using a catheter Simmons type I and
      then we position the top of the catheter beyond the ostium of the spermatic vein
      to fulfil the renal left vein by means of the administration of contrast iodized
      and gonadal vein could be visualized using retrograde phlebography. Transcatheter
      embolization will carry out across the introduction of coils (approximately from
      6 to 8) of 0.038 using a hidrofilic catheter of 4 or 5F. Of the total of the 37
      cases, we obtained correctly embolization in 33 patients (89.2%), being necessary
      a reembolization in three cases (10.8%) of which one finished in surgery. Only in
      a case (2.7%) surgery was practised for embolization incomplete.

PMID- 23155654
TI  - [Urethral polyposis in adolescence].
AB  - Polyps in the urinary tract are a rare entity in infants and children. The most
      frequent location when they appear is the ureter. These benign lesions with no
      malignant potential have a varied form of presentation and in most cases must be
      distinguished from malignancy. The suspected diagnosis is due to urinary
      obstruction; nevertheless radiological evidence played a key role in the final
      diagnosis. The management is as less invasive as possible, with endoscopy
      resection or minimally invasive surgery.

PMID- 23155655
TI  - [Crossed testicular ectopia in indigenous child].
AB  - The crossed testicular ectopia is an extremely rare entity, characterized by
      migration of both testicles in the same inguinal canal, often associated with
      symptomatic inguinal hernia and cryptorchidism in the contralateral side. About
      one hundred cases have been published in the literature. We report a case of
      crossed testicular ectopia in brazilian indigenous boy, aged two years old, with
      a favorable post operative.

PMID- 23155656
TI  - [Management of penile trauma from compressed air gun in a child].
AB  - We report on a 6-year old child with a penile injury resulting in the inclusion
      of a pellet in the cavernous body, by a fortuitous shot. Conservative approach
      with elective extraction of the bullet and cavernous body repair led to a
      satisfactory result, in better anatomic conditions. The patient did not have any
      perioperative complication. Accidents by air weapons are particularly important
      in children, because these weapons are erroneously considered as toys. Air gun
      injuries to head, neck and thorax have been often published, but these injuries
      are rare in the chidren genitourinary area.

PMID- 23155657
TI  - [Surgical closure of ductus arteriosus in the extreme or very extreme preterm
      infant].
AB  - OBJECTIVES: The surgical close of patent ductus arteriosus in the extreme or very
      extreme premature presents difficulties, because of its anaesthesia, surgical
      intervention and the clinical circumstances that usually accompany this
      pathology. We reviewed our experience in order to understand the factors that
      have contributed to the obtained results. METHODS: In all the reviewed patients
      we evalue: gestational age, birth weight, drug treatment, surgical close,
      incidence of bronchopulmonary dysplasia, necrotizing enterocolitis and renal
      failure, time of hospitalization, mortality and its causes. RESULTS: The sample
      is constituted of 26 prematures whose average gestational age is 26.24 weeks and
      average weight 885 g. 22 were treated with indomethacin, at an average age of 7
      days, and all of them underwent surgical close, at an average age of 19 days (0
      50). 10 patients suffered bronchopulmonary dysplasia, operated when they were 28
      days of life. 7 suffered renal failure, 5 of them after drug treatment. 6
      suffered necrotizing enterocolitis. 7 died (27%), 3 of them because of
      prematurity and preoperative severe pathology, 2 because of heart disease, and 2
      because of severe necrotizing enterocolitis. CONCLUSIONS: Surgical ligation of
      patent ductus arteriosus in these patients is well tolerated, especially if the
      attention to prevent bronchopulmonary dysplasia, necrotizing enterocolitis and
      renal failure is optimized. Mortality in our series is not very different from
      that provided for the total of prematures with similar gestational age and birth
      weight, regardless of their pathology.

PMID- 23155658
TI  - [Results of living donor kidney transplant in pediatric recipients, with graft
      obtained by laparoscopy].
AB  - OBJECTIVE: Analyze the results of the living related donor kidney transplant
      (LRDKT) in our center. PATIENTS AND METHODS: Between December 2005 and 2008, 34
      kidney transplants in pediatric recipients were performed in our center, 7
      (20.58%) of which were LRDKT with grafts obtained via laparoscopy. The donor was
      the mother in 4 cases and the father in 3. Mean age of the donors was 43 years
      (38-48) and of the recipients 12.5 years (9-17). Four were a first transplant
      (one of them planned) and three retransplantations. RESULTS: Cold ischemia time
      was < 2 hours in every case while warm ischemia did not show significant
      differences with the cadaveric donor transplant. None had initial graft
      dysfunction. No vascular complications occurred, but there was a urinary fistula
      secondary to ureteral necrosis, resolved with a new reimplantation. Survival of
      the patient and graft is 100%, superior to that of the cadaveric grafts within
      the same period. Current mean plasma creatinine is 0.8 mg/dl (0.7-1.39) and mean
      creatinine clearance is 80 cc/min/1.73 m2 (75-90). No donor had surgical
      complication and all maintain good kidney function. CONCLUSIONS: The short term
      results of the LRDKT with grafts obtained by laparoscopy in our center are
      similar to those described by groups with large experience, which makes it
      possible to continue offering it with guarantee.

PMID- 23155659
TI  - [Ten years of laparoscope hernia repairs. Indications and results].
AB  - INTRODUCTION: The inguinal hernia surgery is common in the pediatric population
      although laparoscopic management today, is not considered the standard technique.
      The aim of this study is to review the results of our study and evaluate the
      contralateral side in patients with unilateral hernia. MATERIAL AND METHODS:
      Retrospective study of laparoscopic herniorraphy at our hospital since the
      beginning of the art in 1999 with a total of 348 patients. The indications of
      laparoscopy have been the availability of umbilical hernia associated, doubt
      diagnosis, recurrence of open surgery, bilateral tumor and casual diagnosis. We
      analyzed the following parameters: sex, age, weight, associated diagnosis, intra
      and postoperative complications, recurrence and follow-up. RESULTS: 474 hernias
      were repaired laparoscopically in 348 patients. A predominance of males against
      females (30%). In 37 patients (11%) the diagnosis was made during another
      operation. 39 patients with recidive open surgery were operated by laparoscopy.
      We had only 2% intraoperative complications and 2% of recurrences. The follow-up
      period is 10 years. CONCLUSIONS: Laparoscopic herniorraphy may be a routine
      procedure with results comparable to open surgery. Laparoscopy offers a good
      overview of the anatomy, easily identifying the defect, with a technique
      increasingly used in the field of pediatric surgery.

PMID- 23155660
TI  - [Cervical cystic lymphangioma: still a challenge].
AB  - INTRODUCTION: Cervical lymphangiomas can not only cause severe sequelae
      (aesthetic, phonatory or deglutory) but can also be life thereatening due to
      airway compresion or massive bleeding. This paper analyzes our surgical results,
      the value of prenatal diagnosis and the use of new techniques such as the EXIT
      procedure for airway control in sereve cases. PATIENTS AND METHODS: We
      retrospectively reviewed the medical record of patients with cervical
      lymphangiomas treated in our center between 1986 and 2009, according to our
      Clinical Documentation Database. Data referred to prenatal diagnosis, intrapartum
      airway management, surgical procedures and morbidity, sclerosing substance
      infiltration and long term sequelae was analyzed. RESULTS: Thirteen cases were
      identified. 53.8% of the patients were diagnosed by prenatal ultrasound, and MRI
      was performed in 46.1%. The tongue was affected in 30.7%, parotid glands in 38.4%
      and airway in 38.4%. Four EXIT procedures were carried out (nasotracheal
      intubation) and one emergency tracheotomy was needed. Five patients required more
      than one surgical prodedures, including partial glossectomy, with severe
      intraoperatory complications in 23% (bleeding, pharyngeal damage). In eight
      patients primary or adyuvant sclerotherapy was used. Three children with giant
      masses died, two due to intracystic bleeding and one from sepsis. Among the
      survivors, 50% have no sequelae. CONCLUSIONS: Cervical lymphangiomas are a very
      sereve condition, not only due to possible airway compresion or massive bleeding
      but also becose of the severe secualaes they may cause. Tongue or parotid gland
      infiltration are difficult to treat. In severe cases diagnosed prenatally a close
      follow up in selected centers, with multidisciplinary teams consisting of
      obstetricians and pediatric surgeons, trained in the EXIT procedure is warranted.
      Despite therapeutic efforts the prognosis of large masses is still poor.

PMID- 23155661
TI  - [Evaluation of the long-term results of surgical treatment of palmar
      hyperhidrosis].
AB  - INTRODUCTION: Palmar hyperhidrosis (PH) is a relative frequent pathology which
      basically affects patients' life quality limiting social and laboral life. The
      treatment of choice is thoracoscopic sympathectomy, most frequently done during
      adulthood. The aim of our study was to evaluate the degree of satisfaction of the
      pediatric patients treated in our centre. MATERIAL AND METHODS: We
      retrospectively reviewed the clinical records of the patients controlled and
      treated in our centre during the last 4 years evaluating the symptoms before
      surgery, the level of the sympathectomy and postoperative complications. To
      evaluate the long-term results we developed a telephone questionnaire for all the
      patients centralized on the grade of satisfaction, the efficiency of the
      treatment, the compensatory sweating and the observed changes in life quality.
      The medium follow-up time was 26.5 months (rango 6 months to 4 years). RESULTS:
      In total 6 patients were reviewed (4 female, 2 male), medium age 12, 8 years
      (rango 8 to 18 years). Thoracoscopic sympathectomy was done at the level of T2 or
      T3 associating T4 in 1 case. We just observed 1 postoperative complication which
      consisted in a disestesia of the upper extremity and which disappeared
      spontaneously without sequels. Patients referred total relief of palmar sweating.
      Only 1 case reported residual sweating unilaterally in the tenar region, but in
      all of them sweating of feet still persisted (3 of low grade and 3 of moderate
      grade). In 50% of the cases we observed compensatory sweating localized at the
      back of moderate grade in 2 patients and at the upper legs of more severe grade
      in 1 of them. Only this last patient reported that the compensatory sweating
      affected his everyday life. We also observed that the patients where the
      sympathectomy had affected more than 1 ganglia (T2+T3; T3+T4; T2+T3+T4) referred
      a higher grade of compensatory sweating. All the cases reported an important
      improvement in life quality, in the social as in the formative manner. They were
      all very satisfied with the results of the surgery and none of them (neither the
      children nor the parents) regretted the intervention. The cosmetic result of the
      surgical scars was also satisfactory. CONCLUSIONS: The thoracoscopic
      sympathectomy is an efficient procedure for the treatment of palmar
      hyperhidrosis. Despite the compensatory sweating patients usually are very
      satisfied with the results. Since palmar hyperhidrosis is not a pathology which
      improves spontaneously and the surgical treatment has minimal complications we do
      not think that the surgery should be postponed in pediatric patients.

PMID- 23155662
TI  - [Treatment of chronic ischial ulcer in the pediatric patient refractory to
      conventional treatments].
AB  - BACKGROUND: Pressure ulcers are an emerging disease, due to survival increase of
      pediatric patients at risk (myelomeningocele, infantile cerebral paralysis,
      paraplegic, prematures with neurological sequelae, etc.), including as well, long
      time staging patients at intensive care units. OBJECTIVES: Provide for long-term
      treatment to pressure ulcer refractory to debridement procedures. METHODS: We
      used the biceps femoris muscular flap technique associated with fasciocutaneous
      flap in two patients, 16 year-olded, with tetraparesis secondary to cerebral
      palsy and, another 18 year-olded, with myelomeningocele sequelae. Both had
      sciatic ulcers refractory to treatment, 2 and 3 years evolutioned, respectively.
      RESULTS: The outcome was excellent in both cases, with definitive healing of the
      ulcer and no recurrence during one and two month follow-up. CONCLUSIONS: This
      technique, used in adults, can be applied to pediatric patients if no possibility
      of wandering. Muscle acts as a cuff between bone and skin and provides coating to
      the zone suffering pressure as an hypervascularized and no-functioning for active
      movement structure, but feasible in terms of trophism.

PMID- 23155663
TI  - [Indication for early excision of the giant congenital nevus].
AB  - INTRODUCTION: Most of specialists involved in giant congenital nevi (GCN) care,
      agree that the risk of melanoma is probably not significant enough to warrant the
      prophylactic removal of all those lesions. However, many patients benefit from
      very early surgical procedures. MATERIAL AND METHODS: In the last 15 years 41
      children undergwent surgical removal of their large or giant melanocityc lesions
      in the first year of life at our institution. Indications for such an early
      excision were as follows: painful ulceration or bleeding, alarming dermatoscopic
      changes, location in the scalp being removable with primary closure, concomitant
      surgical procedures, multiple expected interventions and severe parental
      psychosocial distress. RESULTS: All patients had a good cosmetic result. All
      nevus in the scalp between 3 and 5 cms were removed with a primary closure in
      order to avoid future need of scalp expansion. Familial psychological distress
      improved significantly and disturbances related to scholar activities were not
      noticed. CONCLUSIONS: Despite the lack of international consensus regarding the
      appropriate timing for large or giant congenital nevi excision, a selection of
      patients and their families can benefit from early surgical removal.

PMID- 23155664
TI  - [Results of the use of laparoscopic anti-reflux procedure for the prevention of
      episodes of apnea, bradycardia and desaturation].
AB  - In 1986 the National Institutes of Health Consensus Developement Conference on
      Infantile Apnea and Home Monitoring defined the Apparent Life Threatening Events
      (ALTEs) as those frightening episodes for the observer which are determined by a
      combination of apnea (central or obstructive), changes in colour (cianosis,
      congestive pallor) and marked changes in muscular tone, asphyxia. Despite the
      fact that its cause still remains unknown, many centres relate ALTE with
      gastroesophageal reflux disease (GERD) and therefore recommend medical treatment
      of GERD to those patients with ALTE. However there are very few articles that
      proof the efficacy of surgical treatment in patients with ALTE and GERD. We
      carried out a retrospcective review between 2000 and 2008 of those patients with
      ALTE who underwent a laparoscopic antirreflux procedure. The study included the
      realization of contrast x-ray, pHmetry and laryngeal, digestive and bronchial
      endoscopy. During this period antirreflux (with either Nissen or D'Or technique)
      procedure was carried out by laparoscopic approach in the patients with ALTE and
      GERD. Median of gestational age was 32 week, mean birth weight was 1800 g, mean
      age at the time pof surgery was 217 days (range 32-410). All these patients had
      previously presented 3 or more events of ALTE and had been treated medically for
      GERD. pHmetric studies were no conclusive, In 6 out of 15 patients had different
      grades of arithemoid oedema. All the patients presented gastroesophageal reflux
      (grades II-III) in the constrast x-ray. Mean follow up was 1258 days. 7 from 8
      patients presented clear improvement. Morbimortality derived from surgery was
      null.

PMID- 23155665
TI  - [The fetal ultrasonography in the second quarter: interest for the pediatric
      surgeon].
AB  - INTRODUCTION: The paediatric surgeon should know the details of prenatal
      ultrasound diagnosis to participate in advising parents about the continuation of
      the pregnancy, and to plan the prenatal and postnatal treatment. Our objectives
      are: to determine the incidence of congenital anomalies detected with ultrasound
      in the 2nd trimester, the number of these diagnoses which is confirmed at birth
      and what is the usefulness of this test when advising parents. PATIENTS AND
      METHODS: We reviewed the prenatal ultrasound in 2nd trimester reports made from
      January 2005 to July 2009. We note the ultrasound findings, the maternal and
      gestational age. The evolution of anomalies of the fetuses and the number of
      spontaneous and volunteers abortions are noted. Finally, the diagnoses are
      checked in the newborns. RESULTS: 10,256 ultrasonographies are made in this
      period. 209 stories of pregnant women (2%), which present fetal pathology
      amenable to general surgical treatment, are accessible for study. These include:
      182 urologic disorders (85.44%), 13 digestive disorders (6.1%), 6 thoracic
      disorders (2.8%), 6 multiple malformations (2.8%), 4 maxillofacial disorders
      (1.88%) a sacrococcygeal teratoma (0.47%), an umbilical cord cyst (0.47%), 7
      pregnancies are spontaneous abortion and 7 are terminated voluntarily. 183
      stories of newborns are reviewed, we can confirm 48 uropathies (26.37%), 4
      digestive malformations (30.77%), 4 thoracic disorders (66.66%), 2 maxillofacial
      disorders (50%) and 1 teratoma. CONCLUSIONS: Ultrasonography in the 2nd trimester
      detects almost 2% of specific fetal malformations. False positives are common in
      all diagnostic groups. The number of abortions and the terminations of pregnancy
      is low, most of them are polymalformated fetuses. We believe that ultrasonography
      in the 20th week have low value to counsel the termination of pregnancy, because
      only 7 of the 160 terminations indicated in our hospital during the study period,
      correspond to fetuses with pathology detected in the 2nd trimester. We recognize
      the usefulness of this test but, the false positive and favorable developments in
      a high percentage of fetuses, make us to be cautious to advise the continuation
      of pregnancy and the indication of treatment.

PMID- 23155666
TI  - [Intestinal transplant: in what phase are we?].
AB  - OBJECTIVE: To analyze the evolution of Small Bowel Transplantation program since
      the beginning of the program. MATERIAL AND METHODS: [corrected] All children who
      underwent intestinal transplantation between 1997 and 2009 were retrospectively
      reviewed: epidemiological data, status before transplant, surgical technique,
      immunosupression, results, survival and long.term quality of life were analysed.
      RESULTS: Fifty-two intestinal transplants were performed in 46 children (20
      isolated bowel, 20 combined liver and intestine, and 12 multivisceral); median
      age was 32m (range 7m-19a); weight 12,3 kg (range 3,9-60); 31 had short gut
      syndrome, 8 dismotility, 5 intractable diarrhea, and two were miscellaneous.
      Intestinal adaptation was initially attempted in 26 patients, without success, 20
      were directly listed for transplant. The modality of transplant was modified in
      17 while listed. Baseline immunosupression consisted of tacrolimus and steroids,
      although 5 required conversion to Sirolimus later. Six died during the first
      month, due to sepsis/multiorganic failure (poor status at transplant); 13 died
      during the long-term follow-up. Acute rejection was seen in 20, chronic rejection
      in 3, PTLD in 8 (6 died) and GVHD in 5 patients (3 died). Overall survival after
      5 years of follow-up is 65,2 % (51,7% for the graft). From 2006 to 2008, overall
      patient/graft survival at 6 m, 1 and 3 years after transplant is 88,7/84,1,
      81,2/81,2 and 81,2/71,1%, respectively. After a median follw-up of 39 +/- 29
      months, 27 patients are alive (59%), off TPN, (70% had their ostomy taken down),
      go to school, are scarcely hospitalized and enjoy a good quality of life.
      CONCLUSIONS: Intestinal transplantation has consolided itself as a good choice
      for irreversible intestinal failure, being feasible to achieve a normal life.
      Although overall survival diminishes over time, the center experience has
      improved the results. These patients need a very close follow-up, once transplant
      is over, in order to get an early diagnose of immunological complications.

PMID- 23155667
TI  - [Utility of the ECMO in patients with congenital diaphragmatic hernia].
AB  - At the moment the extracorporeal membrane oxygenation (ECMO) constitutes the last
      link in the therapeutic one of the handling of the respiratory failure in
      patients with Congenital Diaphragmatic Hernia (HDC). We presented our experience.
      From January 2001 we arrange the ECMO in neonative UCI. 76 HDC, 13 (3 rights and
      10 lefts) they have needed ECMO (one in two occasions; altogether 14 procedures).
      Criteria of inclusion: refractory hypoxaemia, oxigenaction index > 40 and weight
      > 2 kg. 5 girls and 8 boys with gestacional age between 35 and 41 weeks (average:
      38) and weight when being born between 2,300 and 3,500 grams (average 2,817). In
      6 cases (5 transferred from other centers) the diagnosis was posnatal. Of the 7
      with prenatal diagnosis, in 4 cases fetal therapy by means of traqueal occlusion
      had been made. Veno-venous in 8 and veno-arterial procedure in 5. Rank of
      duration: 68-606 hours, average of 228.35. The surgery has been made before the
      ECMO in 9 cases, 2 during and 1 later. In an occasion there was no surgery. The
      complications have been of hemorragico type in one patient and infectious in
      three cases with sudden sepsis in one. Precocious mortality has been of 6
      patients and delayed the 2 (total 61%). Although this procedure has the high
      morbi-mortality, it is necessary to consider that is patients very badly
      prognosis without another alternative (with mortality of the 100%). Multicentric
      studies are needed to establish indicators prognoses pre and postbirthdays.

PMID- 23155668
TI  - [Percutaneous gastrostomy: when should antireflux surgery be associated?].
AB  - INTRODUCTION: Percutaneus gastrostomy placement is a procedure widely performed
      in children with failure to thrive or intolerance to oral feeding. At the moment
      of making the indication, the need of an antir-reflux surgery in the same
      procedure comes to question. The aim of this study was to analyse which
      preoperative factors are associated with a higher risk of a posterior
      fundoplication. MATERIAL AND METHODS: We realized a retrospective review of 67
      patients divided in 2 groups (cases and controls) in which a percutaneus
      gastrostomy (PEG) had been made by our service in the period of 1997 to 2008. We
      compared these two groups: Group A (n=11) - patients with severe gastroesophageal
      reflux who required a Nissen procedure afterwards; Group B (n=56) - patients who
      kept without reflux after PEG. We analyzed the different preoperative factors
      that could have been in association to severe reflux after gastrostomy. RESULTS:
      Mean age at the moment of undergoing PEG was 15 months. Mean time of follow up
      was 3,5 years. Only neurological impairment and documented reflux pregastrostomy
      were associated with the need of an antirreflux surgery after PEG. CONCLUSIONS:
      Neurological impairment and documented pregastrosotmy GER could be an indication
      of concurrent antirreflux surgery at the time of gastrostomy.

PMID- 23155669
TI  - [Scarring after Mustarde otoplasty: importance of cures and post-operative follow
      up of the patients].
AB  - INTRODUCTION: In the treatment protocol for patients with Mustarde otoplasties we
      use tennis head sweatbands for 2 months (to be worn all the time in the first
      month and only at night in the second month) to protect the correction obtained
      and to avoid traumatisms. MATERIAL AND METHODS: We describe the cases of 3
      patients who underwent Mustarde otoplasty and presented sloughs in the anterior
      edge of the antehelix that are secondary to the pressure of the compression
      bandage. RESULTS: One patient operated for unilateral malformation suffered
      bilateral scars (in the operated ear and in the healthy one). This prove that the
      scars are secondary to the dressings not to surgery. In two patients the sloughs
      evolved into the formation of nodular hypertrophic scars, which were slowly
      corrected with silicone dressings and externally applied corticosteroids and
      moisturising creams in one patient and had to be resected in the other.
      CONCLUSIONS: It is important to give a detailed explanation to the parents about
      the mission and characteristics of the sweatbands, and also about the need to
      frequently check their correct placing. This is to avoid a complication that,
      without spoiling the final result of the otoplasty, reduces patient satisfaction
      and extends the recovery period.

PMID- 23155670
TI  - A clinican's guide to adult attention-deficit hyperactivity disorder.
AB  - While attention-deficit hyperactivity disorder (ADHD) has been traditionally
      viewed as a childhood ailment, longitudinal data suggest that it persists into
      adulthood for most affected individuals. Adult ADHD is now recognized as a
      legitimate diagnosis with clinical and epidemiological implications. It is
      estimated that 4% of American adults are afflicted by this disorder. There have
      been advances in adultADHD screening tools, diagnostic guidelines, medication
      delivery systems and psychosocial treatments. Despite these gains, there is great
      variability among clinicians in the diagnosis and treatment of adult ADHD. This
      article reviews controversies surrounding the diagnosis and treatment of adult
      ADHD and suggests strategies to overcome existing obstacles.

PMID- 23155671
TI  - Mental-health conditions, barriers to care, and productivity loss among officers
      in an urban police department.
AB  - BACKGROUND: Police officers are frequently exposed to situations that can
      negatively impact their mental health. METHODS: We conducted this study of an
      urban police department to determine 1) the prevalence of post-traumatic stress
      disorder (PTSD), depression, and alcohol abuse; 2) patterns of and barriers to
      mental-health services utilization; and 3) the impact these conditions have on
      productivity loss. RESULTS: Among 150 officers, PTSD (24%), depression (9%), and
      alcohol abuse (19%) were common. Only46.7% had ever sought mental-health
      services; the most commonly cited barriers to accessing serviceswere concerns
      regarding confidentiality and the potential"negative career impact." Officers
      with mental-health conditions had higher productivity loss (5.9% vs 3.4%,
      P<0.001) at an annual cost of $4,489 per officer. CONCLUSION: Mental-health
      conditions among police officers are common, and costly, yet most officers had
      never accessed mental-health services; many due to modifiable risk factors.

PMID- 23155673
TI  - Distal embolization from Mynx device.
AB  - Vascular closure devices are commonly used to obtain arterial access site closure
      after cardiovascular procedures. They are popular as they decrease time to
      hemostasis and ambulation while improving patient comfort by eliminating need for
      compression. However, complications due to vascular closure devices are not
      uncommon. We report a case of possible intravascular distal embolization of water
      soluble PEG polymer that is deployed extravascular using the Mynx vascular
      closure device.

PMID- 23155672
TI  - Ocular manifestations of systemic inflammatory diseases.
AB  - Inflammation of the eye is often times seen in association with systemic
      inflammatory diseases. Understanding the various forms of ocular involvement in
      these conditions is important as untreated ophthalmic involvement can lead to
      severe vision loss. In addition to providing a basic framework for diagnosis and
      treatment, this review will highlight the ocular manifestations of the following
      systemic inflammatory conditions: rheumatoid arthritis, systemic lupus
      erythematosus, Wegener's granulomatosis, Sjogren's syndrome, polyarteritisnodosa,
      primary antiphospholipid syndrome, Behcet's syndrome, Kawasaki disease, Cogan's
      syndrome and relapsing polychondritis.

PMID- 23155674
TI  - Anaphylactic reactions with intravenous vitamin K: lessons from the bedside.
AB  - Vitamin K is used as a correction factor to avert the risk of bleeding due to
      warfarin overdose. Among the reported complications of this therapy, the most
      serious one is the anaphylactic cardiovascular collapse caused by intravenous
      infusion of the drug. We report herein a patient with over-anticoagulation from
      warfarin use and a subcapsular renal bleeding who developed a fatal anaphylactic
      shock after vitamin K administration via slow intravenous infusion. Vigilance
      with the intravenous formulation of this agent should always be sought in order
      to prevent fatal outcomes, especially in patients with severe comorbidities.

PMID- 23155675
TI  - A 26-year-old lady with unexplained ascites: an intriguing diagnosis.

PMID- 23155676
TI  - Typhus syncopalis: an epidemic in Connecticut in 1823.
AB  - In 1825 Dr. Thomas Miner wrote about an epidemic that occurred in Middletown,
      Connecticut in 1823. He called this disease "Typhus syncopalis," sinking typhus,
      or New England spotted fever. Differences in the understanding of disease
      processes in the early 19th century preclude a definitive modern equivalent
      fortyphus syncopalis. In addition, there are disagreements among Dr. Miners'
      contemporaries with regard to fever classification systems. Examination of the
      symptoms and physical findings as described by Dr. Miner suggest the presence of
      encephalitis or meningitis as well as a syndrome resembling a shock-like state.
      Based on symptom comparisons, this paper suggests that typhus syncopalis was
      likely meningococcemia caused by Neisseria meningiditis.

PMID- 23155677
TI  - The president's page. 1962.

PMID- 23155678
TI  - Assisted dying.

PMID- 23155680
TI  - Mentors and mentoring.

PMID- 23155679
TI  - Living in the future.

PMID- 23155681
TI  - Turning words into action.

PMID- 23155682
TI  - Obesity, adolescence, and sleep deprivation.

PMID- 23155683
TI  - 18F-DOPA positron emission tomography/computed tomography application in
      congenital hyperinsulinism.
AB  - Congenital hyperinsulinism (CHI) during infancy is characterized by inappropriate
      insulin secretion resulting in persistent hypoglycemia. This can lead to
      irreversible severe neurological damage in the infant. There are two main
      histologic subtypes: diffuse and focal, both of which may require different
      surgical strategies. It is very important to differentiate focal leisons from
      diffuse leisons. However, the differentiation of diffuse leisons from focal
      leisons is challenging. Affected pancreatic areas utilize dihydroxyphenylalanine
      (DOPA) at a higher rate than normal pancreatic tissues; thus, labeling of L-DOPA
      with fluorine-18 (18F-DOPA) allows functional mapping of hyperinsulinism using
      positron emission tomography/computed tomography (PET/CT). In this article, we
      reviewed the 18F-DOPA PET/CT application in CHI. The aim of this review is to
      enhance the recognition of 18F-DOPA PET/CT application in the diagnosis of CHI.

PMID- 23155684
TI  - Pathogenesis of propylthiouracil-related hepatotoxicity in children: present
      concepts.
AB  - Propylthiouracil (PTU), carbimazole (CMZ) and methimazole (MMI) are the most
      common drugs used today in cases of adolescent thyrotoxicosis. Skepticism has
      been growing regarding the use of PTU in childhood and its association with
      severe liver failure. The aim of this review is to present all the recent data
      regarding pathogenesis of PTU hepatotoxicity in children and adolescents.
      Specifically, reactive drug metabolites and increased oxidative stress can
      directly activate inflammatory and immunological pathways. Drugs are not only
      immunogenic because of their chemical reactivity but also because they may bind
      through electrostatic forces to available T-cell receptors. Redox modulation is
      also a key regulatory strategy in the adaptive immune system. Subtle changes in
      the extracellular redox status may cause profound functional changes in redox
      sensitive proteins. Genetic factors that affect drug biotransformation could also
      be implicated in this mechanistic model of PTU-related hepatotoxicity. Further
      studies are needed to fully understand the pathophysiology of PTU-induced liver
      damage.

PMID- 23155685
TI  - Adhesion of the labia minora in girls: a common disorder that is rarely
      considered.

PMID- 23155686
TI  - Thyroid nodules in children and adolescents: a single institution's experience.
AB  - OBJECTIVE: The aims of this study were to analyze the role of fine-needle
      aspiration biopsy (FNAB) in the management of pediatric thyroid nodules and to
      analyze the malignancy risk of thyroid nodules by studying the association
      between autoimmune thyroiditis and thyroid cancer. METHODS: We conducted a
      retrospective study on 111 patients with thyroid nodules diagnosed in childhood
      or adolescence. FNAB was performed in 46 participants with thyroid nodules after
      ultrasonography (US). Cytology diagnoses were categorized as insufficient,
      benign, suspicious, and malignant. Clinical and surgical follow-up data were
      obtained from medical records. The clinical correlation and accuracy of FNABs
      were evaluated. RESULTS: The family history was positive in four patients. Forty
      six patients had positive antithyroid antibodies and an inhomogeneous
      hypoechogenic US pattern. One patient had previous neck irradiation history.
      Eighty-six patients (%77.5) were euthyroid. All patients underwent US
      examination. The FNAB results of the 46 patients were 29 (63%) benign cases, 7
      (15%) insufficient, and 10 (22%) suspicious patients. Malignancy was not reported
      at all. A repetition of FNAB in two benign cases, which were diagnosed with
      papillary carcinoma during followup, reported these cases as suspicious. Ten
      patients with suspicious FNAB results underwent surgery because of increases in
      the size of the nodules; two patients were diagnosed with papillary carcinoma. In
      this study, the prevalence of malignancy was 4.5% in patients with thyroid
      nodules. CONCLUSION: In this study, the importance of FNAB in the diagnosis and
      follow-up of thyroid nodules in childhood has been observed, and risk factors,
      such as history of familial thyroid carcinoma, radiotherapy to the neck at
      younger ages, suspicious cytological findings, and increased nodular sizes during
      follow-up in cases with Hashimoto thyroiditis have been correlated with increased
      thyroid carcinoma malignancy risk.

PMID- 23155687
TI  - Effects of selenium supplementation in the early stage of autoimmune thyroiditis
      in childhood: an open-label pilot study.
AB  - AIM: The aim of the study was to evaluate the role of selenium (Se) in childhood
      autoimmune thyroiditis regarding its effect on thyroid-stimulating hormone (TSH),
      free thyroxine (fT4), thyroid peroxidase antibodies (TPOAb), thyroglobulin
      antibody (TgAb), and thyroid morphology. METHODS: Newly diagnosed 23 euthyroid
      children (mean age, 12.3 +/- 2.4 years) with Hashimoto thyroiditis (HT) received
      only 50 microg L-selenomethionine per day for 3 months. The baseline basal
      urinary iodine level, serum Se, TSH, fT4, TPOAb, and TgAb concentrations, and
      thyroid morphology by ultrasound were detected. We reanalyzed the TPOAb and TgAb
      changes at the 3rd month and then compared the thyroid morphology with 30 healthy
      individuals (mean age, 12.1 +/- 2.1 years) at the 6th month. RESULTS: Serum
      TPOAb, TgAb, and thyroid echogenicity were unchanged with Se supplementation. A
      prominent decrease in thyroid volume was noteworthy; 35% of patients showed a
      thyroid volume regression rate of > or = 30%. CONCLUSION: In terms of TPOAb and
      TgAb, Se may not benefit in the euthyroid period of HT, but Se supplementation
      seems to lead a favorable response in thyroid volume regression.

PMID- 23155688
TI  - Overestimation of final height prediction in patients with classical congenital
      adrenal hyperplasia using the Bayley and Pinneau method.
AB  - BACKGROUND: A typical growth pattern with decreased pubertal growth spurt has
      been identified in patients with classical congenital adrenal hyperplasia (CAH).
      OBJECTIVE: To evaluate the accuracy of final height predictions in patients with
      CAH using the Bayley and Pinneau (B&P) method. PATIENTS AND METHODS: Using growth
      and final height data of 92 patients (57 F/35 M) with CAH due to 21-hydroxylase
      deficiency (38 SV/54 SW), final height predictions with the B&P method were
      compared to actual final heights. RESULTS: In females, mean final height was
      159.9 +/- 5.3 cm (-1.0 +/- 0.7 SDS) compared to predicted mean final height of
      167.9 +/- 10.7 cm (+0.5 +/- 1.7 SDS), p < 0.001, overestimation 7.3 +/- 9.5 cm.
      In males, mean final height was 170.1 +/- 6 cm (-1.2 +/- 0.8 SDS) compared to
      predicted mean final height of 185.6 +/- 13.4 cm (+1.2 +/- 1.9 SDS), p < 0.001,
      overestimation 13.9 +/- 10.8 cm. CONCLUSION: In classical CAH, final height
      prediction using the B&P method results in significant overestimation of final
      height.

PMID- 23155689
TI  - Is the growth outcome of children with idiopathic short stature and isolated
      growth hormone deficiency following treatment with growth hormone and a
      luteinizing hormone-releasing hormone agonist superior to that obtained by GH
      alone?
AB  - AIM: The aim of this study was to evaluate the effect of combined therapy with
      growth hormone (GH) and luteinizing hormone-releasing hormone agonist (LHRHa) on
      the near-final height (NFH) of children with idiopathic short stature (ISS) and
      growth hormone deficiency (GHD) in early puberty. METHODS: A retrospective
      analysis of 20 patients with ISS and 9 patients with GHD treated with combined
      therapy was undertaken. Twelve children with ISS and ten with GHD, treated with
      GH alone, served as controls. Patients were matched at baseline for chronological
      age, bone age, height standard deviation score (SDS), and pubertal development.
      RESULTS: Patients with ISS or GHD treated with combined therapy improved both
      their predicted adult height (PAH) at 2 years of therapy (ISS, p < 0.001; GHD, p
      = 0.03) and their NFH (ISS, p < 0.05; GHD, p = 0.05). Treatment with combined
      therapy did not generate additional benefits on the PAH after 2 years of therapy
      (ISS children, an increase of 7.9 +/- 4.9 cm with combined therapy vs. 7.3 +/-
      6.0 cm with GH; GHD children, an increase of 6.8 +/- 7.8 cm with combined therapy
      vs. 5 +/- 5.9 cm with GH). The total height gain SDS was higher in patients
      treated with GH alone compared with those with combined therapy, but the
      difference was not significant (ISS children, a gain of 2.4 SDS with GH vs. 0.8
      SDS with combined therapy; GHD children, a gain of 1.8 SDS with GH vs. 0.6 SDS
      with combined therapy). CONCLUSIONS: Although 2 years of combined treatment with
      GH and LHRHa improved the PAH and the NFH of ISS and GHD patients in early
      puberty, this improvement was not significant compared with that observed in
      similar subjects treated with GH alone.

PMID- 23155690
TI  - Molecular defects of the GnRH-receptor gene in Chinese patients with idiopathic
      hypogonadotropic hypogonadism and the severity of hypogonadism.
AB  - BACKGROUND: Human mutations in the gonadotropin-releasing hormone receptor
      (GnRHR) gene cause normosmic idiopathic hypogonadotropic hypogonadism (IHH). At
      least 19 different mutations have been identified in this G-protein-coupled
      receptor, which consist mostly of missense mutations. OBJECTIVES: To identify and
      determine the frequency of mutations in the coding region of the gonadotropin
      releasing hormone receptor (GnRHR) gene in forty Chinese patients with normosmic
      idiopathic hypogonadotropic hypogonadism (IHH) and establish genotype/phenotype
      correlations where possible. METHODS: The diagnosis of HH was based on absent or
      incomplete sexual development after 17 years of age in girls and 18 years in boys
      associated with low or normal levels of LH in both sexes and low levels of
      testosterone in males and of estradiol in females. All patients presented with a
      normal sense of smell in an olfactory specific test. Forty IHH patients and 40
      controls were screened for mutations in the coding sequence of the GnRHR gene.
      The coding region of the GnRHR gene was amplified by PCR and directly sequenced.
      RESULTS: A missense mutation, serine 168 arginine (S168R), located in the fourth
      transmembrane domain of the GnRHR gene, was identified as being in a homozygous
      state in one male with complete HH. The S168R mutation has been previously shown
      to be a cause in the complete loss of receptor function because hormone binding
      to the receptor is completely impaired. In another patient, a compound
      heterozygous mutation (Gln106Arg and Arg262Gln) was identified in a male with
      partial HH. The Gln106Arg mutation is located in the first extracellular loop of
      GnRH-R, this mutation decreases but not does eliminate GnRH binding; while
      Arg262Gln mutation is located in the third extracellular loop of GnRH-R and only
      decreases signal transduction. A good correlation between genotype and phenotype
      was found in our patients. The patient, who was homozygous for the completely
      inactivating S168R mutation, had complete HH. In addition, the affected patient
      who was compound heterozygous for the Glnl06Arg--Arg262Gln mutations - has
      partial HH. CONCLUSIONS: GnRHR mutations can be classified into partial or
      complete loss of function mutations. Partially inactivating substitutions of the
      GnRHR frequently found in familial hypogonadotrophic hypogonadism are Q106R and
      R262Q. Comparison of compound heterozygous with homozygous patients suggests that
      their phenotype and the response to GnRH is determined by the GnRHR variant with
      the less severe loss of function.

PMID- 23155691
TI  - Association of vitamin D receptor gene Cdx2 polymorphism with bone markers in
      Turner syndrome patients.
AB  - BACKGROUND: Turner syndrome (TS) patients usually have low bone mineral density
      (BMD) and increased risk of osteoporotic fractures. We have previously
      demonstrated an association of bb (BsmI polymorphic site) and ff (FokI
      polymorphic site) vitamin D receptor (VDR) genotypes with reduced BMD in TS
      patients. AIM: To analyze the relationship between VDR-Cdx2 polymorphism and BMD
      as well as bone metabolic variables in TS patients. METHODS: Fifty-five TS
      patients and 59 control women were studied. VDR-Cdx2 genotypes were determined
      using TaqMan probes in a real time thermocycler. Lumbar and femoral BMD were
      determined by dual-energy X-ray absorptiometry (DEXA) and serum intact
      parathyroid hormone, osteocalcin and beta3-CrossLaps were determined by
      electrochemiluminescence. RESULTS: Patients with genotype GG had higher levels of
      both osteocalcin and beta-CrossLaps as compared to patients with genotype GA (p <
      0.01 and p < 0.05, respectively). CONCLUSION: Patients carrying genotype GG have
      higher levels of bone formation and resorption markers. This indicates a more
      active bone turnover that could impact on their future bone mineral density.

PMID- 23155692
TI  - Serum 25-hydroxyvitamin D levels do not correlate with asthma severity in a case
      controlled study of children and adolescents.
AB  - BACKGROUND: There is no consensus on the association between vitamin D and
      asthma. OBJECTIVE: To determine the relationship between 25-hydroxyvitamin D
      [25(OH)D] levels and asthma symptom severity in children and adolescents.
      METHODS: A retrospective, case-control study of 263 subjects of ages 2-19 years
      with asthma who were compared to 284 non-asthmatic controls of similar ages.
      Subjects were excluded if they had diseases of calcium or vitamin D metabolism or
      were receiving calcium or vitamin D supplementation. Serum 25(OH)D was measured
      in all subjects. Asthma symptom severity, usually stratified into 6 steps, was
      stratified into five steps [1-5] based on the number and dose of controller
      medications used as outlined by the National Heart, Lung, and Blood Institute's
      guidelines. Mean 25(OH)D values were compared between the asthmatic patients and
      controls, as well as among the five steps of asthma symptom severity. Results
      were adjusted for age, sex, BMI, race and severity of asthma symptoms. RESULTS:
      There was no difference in 25(OH)D between asthmatic patients and controls (28.64
      +/- 10.09 vs. 28.42 +/- 11.47, p = 1.0). However, there was a significant
      difference in 25(OH)D between obese and non-obese asthmatic patients (23.33 +/-
      7.67 vs. 30.16 +/- 10.20, p < 0.0001), as well as obese and non-obese controls
      (24.56 +/- 9.90 vs. 29.50 +/- 11.66, p = 0.003). Mean 25(OH)D levels did not vary
      significantly among the five steps of asthma symptom severity. CONCLUSIONS: There
      were no differences in mean 25(OH) D levels between asthmatic patients and
      controls. Mean 25(OH)D level was significantly lower in both the obese asthmatic
      patients and obese controls. Asthma severity had no relationship to mean 25(OH)D
      levels.

PMID- 23155693
TI  - Assessment of the 21-hydroxylase deficiency and the adrenal functions in young
      females with Turner syndrome.
AB  - There are few reports of an association between Turner syndrome (TS) and 21
      hydroxylase deficiency. However, this association is more frequent in some
      populations. The aim of this study was to evaluate the incidence of 21
      hydroxylase deficiency in patients with TS in our population. 21-hydroxylase
      deficiency was evaluated in 44 TS cases with 45X (n=20) and 24 mosaic cases. A
      standard dose adrenocorticotropic (ACTH) stimulation test (Synacthen, Novartis,
      Basel, Switzerland) was performed, and 17 hydroxyprogesterone (17OHP),
      dehydroepiandrosterone sulfate (DHEAS) and cortisol responses were evaluated.
      Patients with increased 17OHP responses in the stimulation test also underwent 21
      hydroxylase gene analysis. The mean age was 14.6 +/- 4 (2.6-22.4); 37 patients
      were on growth hormone (GH) treatment. Nine patients were at prepubertal stage,
      whereas 35 were pubertal (24 on gonadal steroids and 11 spontaneously). Six
      patients were obese. Only one of our patients had a level of 7.5 ng/mL of 17OHP,
      and there was no mutation found in congenital adrenal hyperplasia (CAH) genetic
      analysis. In other cases, peak 17OHP levels were < or = 6 ng/mL. The mean peak
      17OHP was 2.62 +/- 1.48 (1.19-7.5) ng/mL, the cortisol level was 37.6 +/- 8.43
      (23.9-56.2) microg/dL and the DHEAS was 135.2+/- 87.3 (15-413) microg/dL. The
      increased mean basal and peak cortisol levels (20.5 +/- 10.2 and 37.6 +/- 8.4
      microg/dL) were remarkable findings. Whereas basal cortisol was above 20
      microg/dL in 38.7% of patients, exaggerated results up to 56.2 microg/dL were
      obtained in peak cortisol levels. The basal and peak 17OHP cortisol levels were
      not correlated with the presence of puberty, chromosome structure, gonadal
      steroid use, obesity or growth hormone use. This trial suggested that 21
      hydroxylase deficiency was not common among patients with TS in our population.
      Adrenal function should be assessed, at least in the presence of clitoral
      enlargement in patients with TS, particularly if their karyotype does not contain
      a Y chromosome.

PMID- 23155694
TI  - The association of FGF23 levels in obese adolescents with insulin sensitivity.
AB  - BACKGROUND: The fibroblast growth factor 23 (FGF23) is the most important
      hormonal regulator of circulating phosphate levels. Apart from this essential
      role, it may also act as a 'hormone-like' factor involved in glucose and lipid
      metabolism. It is believed to have a potential role in the development of insulin
      resistance. AIM: The aim of the study was to compare FGF23 levels between two
      groups of obese adolescents: insulin resistant and non-insulin resistant.
      PATIENTS: The study included 36 obese, insulin-resistant adolescents (21 boys and
      15 girls) of pubertal age (mean age, 13.95 years; Tanner stage IV or V). The
      control group consisted of 21 obese peers with normal HOMA-IR values. METHODS:
      FGF23 levels were measured in a fasting blood sample by Human Intact FGF-23 ELISA
      Kit (Immunotopics Inc., San Clemente, CA, USA). A standard oral glucose tolerance
      test was performed, which assessed fasting and 120 min postload plasma glucose
      and serum insulin levels; the insulin resistance index HOMA-IR was calculated.
      The definition of insulin resistance was based on a HOMA-IR threshold set for
      adolescents (> or = 3.16). RESULTS: There was a significant inverse correlation
      between FGF23 levels and HOMA-IR (R = -0.26, p < 0.05) in the study group. FGF23
      levels were also significantly lower in the study group (9.8 vs. 11.9 pg/mL, p =
      0.026). CONCLUSIONS: In adolescents with simple obesity and insulin resistance,
      FGF23 levels are lower compared with obese adolescents with normal HOMA-IR.

PMID- 23155696
TI  - Metabolic impact of a ketogenic diet compared to a hypocaloric diet in obese
      children and adolescents.
AB  - BACKGROUND: The effects of carbohydrate-restricted (ketogenic) diets on metabolic
      parameters in children have been incompletely assessed. OBJECTIVE: To compare the
      efficacy and metabolic impact of ketogenic and hypocaloric diets in obese
      children and adolescents. SUBJECTS: Fifty-eight obese subjects were placed on one
      of the two diets for 6 months. METHODS: Anthropometric measurements, body
      composition, oral glucose/insulin tolerance test, lipidemic profile, high
      molecular weight (HMW) adiponectin, whole-body insulin sensitivity index (WBISI),
      and homeostatic model assessment-insulin resistance (HOMA-IR) were determined
      before and after each diet. RESULTS: Both groups significantly reduced their
      weight, fat mass, waist circumference, fasting insulin, and HOMA-IR (p = 0.009
      for ketogenic and p = 0.014 for hypocaloric), but the differences were greater in
      the ketogenic group. Both groups increased WBISI significantly, but only the
      ketogenic group increased HMW adiponectin significantly (p = 0.025). CONCLUSIONS:
      The ketogenic diet revealed more pronounced improvements in weight loss and
      metabolic parameters than the hypocaloric diet and may be a feasible and safe
      alternative for children's weight loss.

PMID- 23155695
TI  - Higher postprandial serum ghrelin among African-American girls before puberty.
AB  - OBJECTIVE: Recent reports suggest that ghrelin regulation may differ by ethnicity
      and age. This study was designed to examine circulating ghrelin among overweight
      female African Americans across different age groups. METHODS: Eleven overweight
      peripubertal girls, 17 overweight pubertal girls, and a control group of 18
      overweight African-American premenopausal women ingested a standard liquid meal
      after an overnight fast. Blood samples were obtained before the meal and for 4 h
      postchallenge. Participants rated appetite by a visual analog scale. RESULTS:
      Peripubertal girls demonstrated higher postprandial ghrelin and lesser ghrelin
      suppression compared with adults (p < 0.05), corresponding with greater desire to
      eat across the test period (p = 0.017). Fasting ghrelin tended to be inversely
      related to fasting estradiol (r = -0.264, p = 0.076). CONCLUSION: Compared with
      overweight African-American women, peripubertal girls had higher ghrelin as well
      as greater appetite after a standard meal. These results may suggest a
      dysregulation in ghrelin reflective of demands of growth.

PMID- 23155697
TI  - The second report from Turkey: waist percentiles for 6-11-year-old children in
      Elazig Province, Eastern Anatolia.
AB  - OBJECTIVE: To construct waist percentiles for 6-11-year-old Turkish children in
      Elazig Province, Eastern Anatolia. METHODS: This cross-sectional study was
      performed with 3342 (1708 boys and 1634 girls) children from March to June 2007.
      Waist circumferences (WC) were measured between the lowest rib and the superior
      iliac crest, and centile curves were constructed with the Lambda-Mu-Sigma (LMS)
      method. RESULTS: Towards 6-11 years, WC 50th percentile ranged from 57.54 to
      67.04 cm in boys and 55.77 to 64.58 cm in girls. For both genders, WC increased
      with age. At each age, boys had higher WC values than girls. For the entire
      sample, mean WC was 62.5 +/- 6.8 cm for boys and 59.8 +/- 6.2 cm for girls.
      Median WC was 62.0 cm (32.0-90.0) for boys and 59.0 cm (46.0-87.0) for girls.
      CONCLUSIONS: The large differences in the values obtained worldwide emphasize the
      necessity of providing population-specific WC reference curves from different
      populations, which in turn may result in an international reference standard
      similar to that provided for body mass index.

PMID- 23155698
TI  - Association analysis between endothelial function related factors and coronary
      artery stenosis degree in coronary heart disease patients with type 2 diabetes
      mellitus.
AB  - OBJECTIVE: To investigate the relationship between soluble intercellular adhesion
      molecule (sICAM-1), vascular endothelial cell adhesion molecule (VCAM-1),
      monocytes chemotactic protein (MCP-1), von Willebrand factor (vWF), and coronary
      artery stenoses degree in coronary heart disease (CHD) within type 2 diabetes
      mellitus (T2DM) patients. METHODS: A total of 92 subjects were treated with
      coronary angiography (CAG), including 62 subjects with CHD. The individuals were
      divided into three groups, group A (32 patients with CHD and T2DM), group B (30
      patients with CHD but no T2DM) and group C (30 patients with no CHD and T2DM).
      All patients were treated with a Gensini coronary angiography check. The
      correlations between sICAM-1, VCAM-1, MCP-1 and vWF in peripheral blood and
      coronary artery stenosis degree were analyzed. RESULTS: The average score of
      coronary artery stenosis degree was 30.75 +/-12.67 in group A, which was
      significantly higher than group B (11.20 +/-7.51) and group C (2.40 +/- 1.23) (p
      < 0.01). The mean levels of sICAM-1, VCAM-1, MCP-1 and vWF in serum showed that
      group A was significantly higher than group B and group C (p < 0.01), and also
      that group B was higher than group C. There were significant positive
      correlations between the degree of coronary artery stenosis and the mean level of
      sICAM-1, VCAM-1, MCP-1, vWF in group A (p < 0.01), but these were not shown in
      group B and group C (p > 0.05). CONCLUSIONS: Association analysis shown that the
      level of sICAM-1, VCAM-1, MCP-1 and vWF elevated in CHD with T2DM patients.
      Vascular endothelial dysfunction could be caused to the coronary artery stenosis
      pathophysiological process. Results from this study suggested that sICAM-1, VCAM
      1, MCP-1 and vWF may contribute to the occurrence and development of vascular
      lesions in T2DM. These endothelial function related factors could be acceptable
      as a prediction and testing index of vascular complications in T2DM.

PMID- 23155700
TI  - Thyroid autoimmunity in 72 children with type 1 diabetes mellitus: relationship
      with pancreatic autoimmunity and child growth.
AB  - The aim of this study was to assess the association between pancreatic and
      thyroid autoimmunity (TA) and determine impact of thyroid antibodies on statural
      growth. Seventy-two children with type 1 diabetes mellitus (TIDM) and no clinical
      evidence of thyroid disorders were evaluated: glycated haemoglobin (A1c), thyroid
      peroxidase antibodies (TPOAb), glutamic acid decarboxylase antibody (GADA),
      tyrosine phosphatase antibodies (IA2A), and thyroid-stimulating hormone (TSH).
      The score of standard deviation for height (SDS) was calculated. There were 72
      patients, 38 (52.7%) boys and 34 (47.2%) girls, with a mean age of 10.89 +/- 4.26
      years and a mean duration of T1DM of 3.41 +/- 2.56 years. TPOAb were present in
      23.6% of patients; 12.5% of subjects were positive for GADA and 41.6% for IA2A.
      Patients with TA had more prevalent GADA and IA2A (23.5% vs. 9%, p < 0.001, and
      58.8% vs. 36.3%, p < 0.001, respectively). A1c was higher in patients with TA
      (9.7% +/- 2.05% vs. 8.6% +/- 2.11%, p = 0.05). TA was associated with lower SDS
      (0.26 vs. 0.98, p = 0.043). TSH was higher in patients with TA (3.39 vs. 2.15
      microU/mL, p < 0.05). Logistic regression analysis revealed that a negative SDS
      for height was independently associated with duration of diabetes (p = 0.049) and
      TSH (p = 0.027) but not with birth weight, A1c, and TPOAb. In conclusion, TA was
      found in 23.6% TIDM children. Patients with TA had significantly higher
      prevalence of GADA and IA2A and significantly higher A1c vs. patients without TA.
      Our data suggest significant association between TA and height in children with
      T1DM. SDS was independently associated with diabetes duration and TSH.

PMID- 23155699
TI  - Adiponectin and arterial stiffness in youth with type 1 diabetes: the SEARCH for
      diabetes in youth study.
AB  - Persons with type 1 diabetes are at increased risk of developing vascular
      disease. Adiponectin concentrations may play an intermediate role in this
      process. We sought to determine whether adiponectin is correlated with vascular
      stiffness in adolescents with type 1 diabetes. Plasma adiponectin, pulse wave
      velocity (PWV), augmentation index (AIx-75), and brachial distensibility (BrachD)
      were collected in 225 adolescents. Outcomes were evaluated by sex, and regression
      models were used to determine whether adiponectin was an independent determinant
      of arterial stiffness. Males had lower adiponectin levels and stiffer vessels
      (lower BrachD, p < 0.01) than females. Unadjusted correlations revealed that
      adiponectin was correlated with BrachD (p < 0.01) but not PWV and AIx-75. After
      adjustment, adiponectin was not a significant predictor of BrachD. The most
      consistent predictors of increased stiffness were age, male sex, blood pressure,
      obesity, and total cholesterol (p < 0.05). Adiponectin's contributions to
      arterial stiffness appear to be masked by other cardiovascular risk factors in
      persons with type 1 diabetes.

PMID- 23155701
TI  - Nesfatin-1 in newborns: relationship with endocrine and metabolic and
      anthropometric measures.
AB  - OBJECTIVE: To explore the relationship between nesfatin-1 and growth and
      development in newborns. METHODS: Blood samples for nesfatin-1, ghrelin,
      insulinlike growth factor-1 (IGF-1), insulin and glucose were obtained from
      preterm (n = 53) and term infants (n = 60), including appropriate for gestational
      age (AGA) (n = 32) and small for gestational age (SGA) infants (n = 28). The
      relationship between nesfatin-1 and other metabolic hormones or anthropometric
      parameters was evaluated. RESULTS: The concentrations of nesfatin-1, ghrelin and
      insulin and the homeostasis model assessment-insulin resistance index (HOMA-IR)
      were higher in SGA than AGA infants (p = 0.0358, 0.0163, 0.0001 and 0.0051,
      respectively), but IGF-1 levels and homeostasis model assessment-insulin
      sensitivity index (HOMA-ISI) were lower (p = 0.033 and 0.0001, respectively).
      Nesfatin-1 levels in SGA infants were higher on postnatal day 0 (PNDO) than in
      AGA infants (p = 0.0358) and lower on PND7 (p = 0.0002) and PND28 (p = 0.0488). A
      negative correlation showed between nesfatin-1 and oral calorie intake (r = 
      0.446; p = 0.017) and HOMA-ISI (r = -0.398; p = 0.036), and a positive
      correlation between nesfatin-1 and HOMA-IR (r = 0.43; p = 0.023) in SGA infants.
      CONCLUSION: Nesfatin-1 is involved in the physiological regulation of
      intrauterine and postnatal growth and development in SGA infants.

PMID- 23155702
TI  - How much is enough? Evaluation of adrenal function in children who undergo growth
      hormone stimulation test.
AB  - The objective was to determine the probability of receiving steroid treatment
      following an insulin tolerance test (ITT) for short-stature evaluation and to
      evaluate the utility of a subsequent cortrosyn stimulation test (CST) in
      determining adrenal sufficiency. We retrospectively analyzed the hypothalamic
      pituitary-adrenal (HPA) axis evaluation in short-stature subjects during the 5
      year period from January 2005 to December 2009. The probability of receiving
      steroid treatment was < 10% when the maximum cortisol concentration during an ITT
      was < 8.4 microg/dL. In the event of a suboptimal cortisol response during an
      ITT, only a single 1-microg CST is recommended for assessment of adrenal
      function.

PMID- 23155703
TI  - A novel mutation in the GCM2 gene causing severe congenital isolated
      hypoparathyroidism.
AB  - OBJECTIVE: To investigate the GCM2 gene in three siblings with congenital
      hypoparathyroidism and perform functional analysis. MATERIALS AND METHODS: We
      sequenced the GCM2 gene by PCR and analyzed the functional consequence of the
      mutation by transient transfection studies. Haplotype analysis was performed.
      RESULTS: We identified a nucleotide change, c.408C>A, in exon 3 that is predicted
      to truncate the Gcm2 protein (p.Tyr136Ter). All three affected siblings were
      homozygous and both parents were heterozygous for the mutation. Transfection
      studies revealed the mutant mRNA but not expression of the Gcm2 protein.
      Haplotype analysis revealed that the two mutant GCM2 alleles shared genotypes on
      chromosome 6p24.2. CONCLUSIONS: We describe the first GCM2 mutation in exon 3 in
      patients with severe congenital hypoparathyroidism. Informative genetic markers
      could not exclude identity by descent for the mutant alleles. Gcm2 protein was
      not detected after transfection, suggesting that complete lack of Gcm2 action
      accounts for severe hypoparathyroidism.

PMID- 23155704
TI  - Relation among ghrelin, nutritional status, and immunity in children.
AB  - BACKGROUND: Ghrelin is an important mediator of energy balance and metabolism.
      The aim of this study was to investigate the relationship among ghrelin
      concentration, growth patterns, and immunological parameters in children with an
      impairment or inefficiency in functioning of the immune system. METHODS: Twenty
      patients with primary immunodeficiency diseases (PIDs), 20 patients with
      recurrent respiratory tract infections (RRTIs), and 20 healthy children (control
      group) were included. The anthropometric measurements, ghrelin plasma levels, and
      selected immunological parameters were measured. RESULTS: Ghrelin levels and
      nutritional status parameters (weight, height, and body mass index) values were
      negatively correlated only in the control group. Ghrelin negatively correlates
      with complement hemolytic activity in the PID group and with IgA serum level in
      the RRTI group. CONCLUSION: Our results show evidence that there is a
      relationship between ghrelin and nutritional status of healthy children but not
      in children with PID or RRTI.

PMID- 23155705
TI  - The histopathological effects of tamoxifen in the treatment of pubertal
      gynecomastia.
AB  - Pubertal gynecomastia is the glandular proliferation of male breast tissue. It is
      regarded as a physiological phenomenon, arising due to a presumed transient
      imbalance in the ratio of free androgen to free estrogen. Treatment with
      tamoxifen, a selective estrogen receptor blocker, has been shown to effectively
      reduce the disc size and is generally considered for treatment when the disc
      diameter is > 3-4 cm. For severe or persistent cases, surgery is considered the
      mainstay of treatment. We present three cases who reported dissatisfaction with
      the results of tamoxifen treatment and were therefore submitted to adenectomy by
      Webster's technique preceded by liposuction. Pathology results showed adipose
      tissue alone, with no evidence of intraductal epithelial proliferation. The
      results showing a lack of residual glandular breast tissue after treatment using
      tamoxifen proves that it is effective in histopathologically eliminating pubertal
      gynecomastia.

PMID- 23155706
TI  - Central precocious puberty after interpersonal transfer of testosterone gel: just
      a coincidence?
AB  - BACKGROUND: Over the last 10 years, several children, fetuses and women have been
      reported to be virilized through interpersonal transfer of testosterone (T) gel
      used by fathers or partners. Long-term exposure to androgens in children, such as
      in poorly controlled congenital adrenal hyperplasia, is known to promote central
      precocious puberty. METHODS: Clinical case report. RESULTS: We report on a 5-year
      old boy who developed central precocious puberty after long-term (starting
      prenatally) exposure to testosterone through interpersonal transfer of T gel used
      by his father. We also report on another case illustrating that the recommended
      precautions are not sufficient to avoid interpersonal transfer of T gel among
      household contacts. Plasma testosterone levels and history-taking revealed the
      cause of virilisation and the testosterone contamination source in both cases.
      Given the increased testicular volume and persisting testosterone elevation after
      cessation of gel use in the first patient, a GnRH test was carried out and
      confirmed central precocious puberty. CONCLUSION: This is the first report of a
      boy with central precocious puberty occurring after long-term (starting
      prenatally) exposure to testosterone through the interpersonal transfer of Tgel.
      This report questions whether central precocious puberty constitutes a long-term
      side effect of testosterone exposure in childhood through T gel use by a
      household contact.

PMID- 23155707
TI  - Elevated alpha-fetoprotein levels in Van Wyk-Grumbach syndrome: a case report and
      review of literature.
AB  - The association between primary hypothyroidism and precocious puberty secondary
      to ovarian hyperstimulation has been recognized for over a century. Here, we
      report the case of a 9-year-old girl with severe primary hypothyroidism, who
      presented with premature menarche, enlarged pituitary gland, enlarged ovaries
      with multiple cysts, and elevated prolactin and alpha-feto protein levels.
      Pituitary and ovarian radiology findings, and alpha-feto protein levels
      normalized a few weeks after hypothyroidism treatment was started. Reviewing the
      literature we found several reports of increased levels of tumor markers in girls
      with this association. Thyroid function tests should be always part of the
      evaluation of patients with precocious puberty especially if the bone age is
      delayed. Tumor markers and liver function tests may be abnormal in patients with
      severe hypothyroidism and improve soon after thyroid hormone replacement is
      started.

PMID- 23155708
TI  - Identification of LDLR mutations in two Chinese pedigrees with familial
      hypercholesterolemia.
AB  - Familial hypercholesterolemia (FH) is an autosomal dominant, inherited disease
      (OMIM 143890) characterized by elevated serum cholesterol bound to low-density
      lipoprotein (LDL). It is mainly caused by mutations of the low-density
      lipoprotein receptor gene (LDLR). In this study, we investigated two Chinese
      pedigrees with FH. The probands were a 9-year-old boy and a 1-year-old boy, who
      had high LDL-C levels. The proband in family A showed skin xanthoma. We sequenced
      the promoter and all exons and exon-intron boundaries of the LDLR gene to detect
      potential mutations. Compound heterozygote of c.1747C>T and c.2054C>T was
      detected in the proband of family A, and a heterozygous indel mutation c.551_553
      delGTAinsTT was discovered in the second family. The c.1747C>T and c.2054C>T
      mutations, which have been reported previously, result in His583Tyr and Pro685Leu
      substitutions, respectively. The novel c.551_553 delGTAinsTT indel mutation
      causes a frameshift, which results in a p.Cys184Phe fs21X mutation in the
      corresponding protein.

PMID- 23155709
TI  - Foster care and type 1 diabetes in the Bronx: a case series.
AB  - OBJECTIVE: The objective of this retrospective study was to describe the health
      status of children with type 1 diabetes mellitus (T1DM) in foster care. RESEARCH
      DESIGN AND METHODS: A retrospective chart review of children with T1DM in foster
      care at the Children's Hospital at Montefiore (CHAM) in Bronx, NY, USA, was
      performed. RESULTS: All patients were either African American or Hispanic and
      raised by single mothers. The majority of referrals were for medical neglect. The
      time spent in foster care ranged from 1 to 7 years, with 1-12 placements. Only
      two children were reunified with their biological mothers. Extensive financial
      burdens on the health-care system for children with diabetes including prolonged
      hospitalizations awaiting placement, frequent hospital admissions, and support
      services were noted. CONCLUSIONS: To our knowledge, this is the first report on
      children with T1DM in foster care. Poor glycemic control and suboptimal social
      outcomes were noted in the children we report in our case series. Programs geared
      to improve and reform foster care for children with diabetes are needed.

PMID- 23155710
TI  - Primary hyperparathyroidism: fifth parathyroid intrathymic adenoma in a young
      patient.
AB  - The clinical case described in this paper deals with a young female patient
      affected by primary hyperparathyroidism caused by an ectopic parathyroid adenoma
      of a supernumerary intrathymic parathyroid. The patient had hypercalcemia, in
      association with increased levels of parathormone, but was otherwise
      asymptomatic. Genetics tests for mutation of the MEN1, HRPT2, and CaSR genes were
      negative. She therefore underwent laboratory and instrumental tests but
      localization results in the neck were negative--only an intrathymic nodule was
      visualized. The complete surgical ablation of the thymus was conducted, which
      highlighted a nodule that, at histological examination, was shown to be an
      adenoma of a fifth parathyroid gland. The existence of a fifth, hyperfunctioning,
      intrathoracic parathyroid appears to be a rare cause of primary juvenile sporadic
      hyperparathyroidism. This peculiar clinical case could be of interest in similar
      cases evaluated by other surgeons.

PMID- 23155711
TI  - Sturge-Weber syndrome: presentation with partial hypopituitarism.
AB  - Sturge-Weber syndrome (SWS) is a rare disorder involving central nervous system
      abnormalities. It manifests with a facial port-wine birthmark and a vascular
      malformation of the brain. Infants and children present with seizures and stroke
      like episodes with focal neurologic deficits. Patients with Sturge-Weber syndrome
      carry the additional risk of developing hypothalamic-pituitary dysfunction,
      secondary to their central nervous system dysfunction. Although one would suspect
      the hypothalamic-pituitary axis would be at risk for impairment given the
      abnormalities that often occur in Sturge-Weber syndrome, they are not commonly
      recognized by clinicians. Increased awareness of this potential complication in
      patients with this rare disease of Sturge-Weber syndrome is needed. We hereby
      report a case of SWS with partial hypopituitarism and consider it to be important
      that these patients should undergo routine evaluation of pituitary function in
      the face of any relevant clinical manifestations.

PMID- 23155712
TI  - Self-limiting hematuria following growth hormone provocative testing with
      arginine hydrochloride.
AB  - Evaluation of growth hormone (GH) deficiency often involves use of agents that
      stimulate GH secretion, such as clonidine, glucagon, insulin, levo-dopa or
      arginine hydrochloride. We present three pediatric cases of benign, macroscopic
      hematuria in children without pre-existing renal disease following GH stimulation
      testing with clonidine and arginine hydrochloride. In all cases hematuria
      resolved spontaneously within 3-4 days without any intervention. This suggests
      that careful observation in such cases is sufficient and additional costly
      evaluation may be avoided. Other than six anecdotal cases registered via on-line
      adverse event reporting system (AERS), this is the first published report to date
      of painless, macroscopic, self-limiting hematuria after arginine hydrochloride
      infusion.

PMID- 23155713
TI  - First case report of short-chain acyl-CoA dehydrogenase deficiency in China.
AB  - Short-chain acyl-CoA dehydrogenase deficiency (SCADD) is a rare autosomal
      recessive inborn error of mitochondrial fatty acid oxidation. It is caused by
      rare mutations as well as polymorphic susceptibility variants. We describe here
      the case of a 1-year-old male patient who had growth and mental retardation,
      seizures, and recurring fever since infancy. Urinary gas chromatography/mass
      spectrometry (GC/MS) showed elevated levels of ethylmalonic acid. Plasma
      acylcarnitines on tandem mass spectrometry (MS/MS) and elevations of C4
      cartinitine are consistently present. The two polymorphic susceptibility variants
      of the short-chain acyl-CoA dehydrogenase (SCAD) gene, c.625G>A and c.322G>A,
      were detected. Because of its highly variable clinical characteristics, there are
      no related reports in China. This report broadens the phenotype and genotype of
      SCADD in China and underlines the difficulty of diagnosis.

PMID- 23155714
TI  - Ganglioneuroblastoma in a young child with Turner syndrome.
AB  - X chromosome aneuploidy has been identified as a potential risk factor for the
      development of neuroblastic tumors. We report a case of a 4-year-old girl with a
      45,X karyotype incidentally discovered to have a large ganglioneuroblastoma on
      initial screening ultrasound. The incidence of these tumors in girls with Turner
      syndrome as well as their possible relationship to recombinant human growth
      hormone treatment is discussed.

PMID- 23155715
TI  - MODY2 caused by a novel mutation of GCK gene.
AB  - Maturity-onset diabetes of the young type 2 (MODY2) is an autosomal dominant
      inherited disease caused by heterozygous inactivating mutations in the
      glucokinase (GCK) gene and is characterized by mild noninsulin-dependent fasting
      hyperglycemia. It is treated with diet only, and complications are extremely
      rare. We present a report of a family with MODY2 caused by a novel
      NM_000162.3:c.878T>C mutation in exon 8 of the GCK gene. Testing for MODY2 and
      reporting all novel mutations are important to avoid difficulties in the
      interpretation of genetic test results and to provide fast and definitive
      diagnosis for all patients with this disease.

PMID- 23155716
TI  - Variability in the age at diagnosis of diabetes in two unrelated patients with a
      homozygous glucokinase gene mutation.
AB  - Homozygous mutations in the glucokinase gene (GCK) result in a complete
      deficiency of the GCK enzyme, which leads to permanent neonatal diabetes
      mellitus. Whilst there has been one report of a patient (with a homozygous
      p.T168A) who was diagnosed with diabetes at the age of 2 months, all other cases
      were diagnosed with diabetes within the first 2 weeks of life. We now report a
      second unrelated patient with the same p.T168A GCK mutation who was diagnosed
      with diabetes at the age of 9 months. We conclude that the specific GCK mutation,
      as yet unidentified genetic modifiers, and/or environmental factors might have
      different effects on pancreatic beta-cell functions, causing variability in the
      age at diagnosis of diabetes.

PMID- 23155717
TI  - Understanding less than nothing: high-dose vitamin D therapy for treating vitamin
      D deficiency.

PMID- 23155718
TI  - Risk of violent crime victimization during major daily activities.
AB  - Exposure to risk of violent crime is best understood after considering where
      people are, what they do, and for how long they do it. This article calculates
      Americans' exposure to violent attack per 10 million person-hours spent in
      different activities. Numerator data are from the National Crime Victimization
      Survey (2003-2008) estimates of violent incidents occurring during nine major
      everyday activities. Comparable denominator data are derived from the American
      Time Use Survey. The resulting time-based rates give a very different picture of
      violent crime victimization risk. Hour-for-hour, the greatest risk occurs during
      travel between activities. This general result holds for demographic subgroups
      and each type of violent crime victimization.

PMID- 23155719
TI  - Social capital, opportunity, and school-based victimization.
AB  - This study extends the opportunity theory of victimization to consider the social
      capital of adolescents at school. We argue that social capital might act as a
      protective factor potentially encompassing both the concepts of guardianship and
      target attractiveness. Drawing on a sample of 5395 adolescents interviewed in the
      context of the 2007 National Crime Victimization Survey (school crime
      supplement), we develop school-specific measures of social capital and
      opportunity indicators in predicting violent and theft victimization on school
      grounds. The results show that opportunity indicators are strong predictors of
      both violent and theft victimization and that social capital is especially
      important as a protective factor from violent victimization. More specifically,
      the results indicate that students who developed trust relationships with adults
      at school benefit from these relationships by avoiding violent encounters with
      potential offenders. Implications for opportunity theories of victimization are
      discussed.

PMID- 23155720
TI  - Recent victimization experiences and continued criminal behaviors: what are the
      links for adult drug-involved offenders?
AB  - Using data from the multi-site adult drug court evaluation (MADCE), we examined
      the relationship between recent victimization experiences and the likelihood of
      subsequent criminal behavior among a sample of adult drug-involved offenders. The
      MADCE data used in this study involved interviews with 674 men and 284 women at
      baseline and then, 18 months later. Multilevel modeling showed that physical
      victimizations in the year before baseline, but not sexual victimization
      experiences, were associated with self-reported criminal offending behavior 18
      months later. All relationships held true despite controlling for respondents'
      demographic, criminal history, prior drug-related characteristics, and their
      participation in a drug court or comparison site program.

PMID- 23155721
TI  - The difficulty in measuring suitable targets when modeling victimization.
AB  - Target suitability is a critical theoretical concept for opportunity theory.
      Previous research has primarily measured this concept using demographic
      characteristics of the study participant, which is problematic. This study
      corrects the measurement problem by employing bullying variables as alternative
      measures of target suitability because they are arguably better at capturing the
      social and psychological vulnerability of the individual that is attracting
      motivated offenders. Using three waves (1999, 2001, & 2003) of the National Crime
      Victimization Survey (NCVS) School Crime Supplement (SCS), this research explores
      the impact of the bullying measures along with demographic characteristics and
      lifestyle measures on the likelihood that a student will experience victimization
      in school. The findings suggest that the bullying measures are better predictors
      of victimization over the demographic characteristics and lifestyle measures for
      all three waves. The findings highlight the need for better measures of target
      suitability, which capture the social and psychological vulnerability of victims
      to explain victimization.

PMID- 23155722
TI  - Patterns of victimization between and within peer clusters in a high school
      social network.
AB  - This study presents a descriptive analysis of patterns of violent victimization
      between and within the various cohesive clusters of peers comprising a sample of
      more than 500 9th-12th grade students from one high school. Social network
      analysis techniques provide a visualization of the overall friendship network
      structure and allow for the examination of variation in victimization across the
      various peer clusters within the larger network. Social relationships among
      clusters with varying levels of victimization are also illustrated so as to
      provide a sense of possible spatial clustering or diffusion of victimization
      across proximal peer clusters. Additionally, to provide a sense of the sorts of
      peer clusters that support (or do not support) victimization, characteristics of
      clusters at both the high and low ends of the victimization scale are discussed.
      Finally, several of the peer clusters at both the high and low ends of the
      victimization continuum are "unpacked", allowing examination of within-network
      individual-level differences in victimization for these select clusters.

PMID- 23155723
TI  - Does the relationship between depression and intimate partner aggression vary by
      gender, victim-perpetrator role, and aggression severity?
AB  - Research has shown a consistent link between intimate partner violence (IPV) and
      depression, although this association may vary by gender, role in IPV (victim,
      perpetrator, or bidirectional), and aggression severity. We evaluated these
      factors in a telephone survey of 14,063 Canadians. All three factors were found
      to affect the association of depression with IPV. Specifically, depression was
      more strongly associated with IPV by a partner (i.e., victimization) for women
      but with aggression toward a partner (i.e., perpetration) for men. Severity of
      aggression was associated with increased risk of depression for both one-sided
      and bidirectional aggression by a partner but more strongly for one-sided
      aggression toward a partner. These findings suggest that research, prevention,
      and treatment should focus on all roles in IPV, not just male-to-female
      aggression.

PMID- 23155724
TI  - Multiple victimization experiences, resources, and co-occurring mental health
      problems among substance-using adolescents.
AB  - This study examined the relationship between multiple types of victimization
      experiences, psychological and social resources, and co-occurring mental health
      problems among substance-using adolescents. Data for this cross-sectional study
      were obtained from a multisite research project in which adolescents ages 11-18
      years participated in a comprehensive screening program for substance misuse.
      Multiple types of victimization, low self-efficacy beliefs, lack of support for
      victimization issues, and available sources of emotional support were positively
      related to co-occurring mental health problems. These findings suggest that
      treatment planning and interventions may focus on helping adolescents cope
      effectively with their victimization experiences and addressing their mental
      health needs. Particular emphasis may be placed on enhancing self-efficacy and
      social skills so that adolescents may benefit from their available sources of
      social support.

PMID- 23155725
TI  - A prospective investigation of the relationship between child maltreatment and
      indicators of adult psychological well-being.
AB  - The study of psychological well-being will advance understanding of child
      maltreatment effects and resilience processes. In this study, the mean level of
      anger in adulthood was significantly higher for those identified three decades
      earlier as having been maltreated. Mean levels of self-esteem, autonomy, purpose
      in life, perceived (fewer) constraints, and happiness and satisfaction were lower
      for those who were maltreated according to child welfare reports. Officially
      recorded child maltreatment was moderately (r < .30) correlated with several
      psychological well-being indicators and predictive of adult anger, self-esteem,
      autonomy, and happiness/life satisfaction after accounting for childhood
      socioeconomic status (SES), gender, and other sources of data on child abuse and
      neglect. Parent-reported abusive disciplining also uniquely predicted several
      outcomes, as did a measure of observed child neglect to a lesser extent.

PMID- 23155726
TI  - An examination of general aggression and intimate partner violence in women with
      posttraumatic stress disorder.
AB  - Research has documented significant relationships between posttraumatic stress
      disorder (PTSD), aggression, and intimate partner violence (IPV). Most of these
      studies have focused on men and measured violence by self-report. This study
      examined (a) the association between PTSD and general aggression among women, (b)
      the association between IPV and PTSD among married and/or cohabitating couples,
      and (c) the concordance between self and collateral reports of IPV. One hundred
      twenty participants provided information about PTSD symptoms and general
      aggression toward others, and 43 married and/or cohabitating couples provided
      information about PTSD and IPV. Women with PTSD reported more general aggression,
      IPV perpetration, and IPV victimization. Collateral informants of those with and
      without PTSD did not differ significantly in their report of IPV. Concordance
      between participants and spouses or partners was low to moderate. These results
      are discussed within the context of extant IPV literature.

PMID- 23155728
TI  - Assessing the relationship between alcohol outlets and domestic violence: routine
      activities and the neighborhood environment.
AB  - Studies have consistently found a positive relationship between alcohol outlet
      density and assault, but only a handful of studies have examined whether outlet
      density has an influence on domestic violence. Using a framework based in crime
      opportunity theories, this study estimates spatial econometric regression models
      to test whether the density of alcohol outlets across neighborhoods is positively
      associated with police calls for service for domestic violence. Models also were
      developed to test whether the relationships found were consistent across time
      periods associated with the use of alcohol outlets (weeknights and weekends). The
      findings indicate that off-premise outlets were associated with a significant
      increase in domestic violence, but on-premise outlets (specifically restaurants
      and nightclubs) were associated with a decrease in domestic violence. The risk
      for domestic violence in areas of high densities of off-premise outlets was found
      to be high during the weekend but not during the weeknight, suggesting different
      routine activities for domestic violence offenders during the week.

PMID- 23155727
TI  - Correlates of serious violent crime for recently released parolees with a history
      of homelessness.
AB  - This study used baseline data on recently released paroled men who are homeless
      (N=157), residing in a residential drug treatment program, and enrolled in a
      longitudinal study to examine personal, developmental, and social correlates of
      parolees who are homeless and who have committed serious violent offenses. Having
      experienced childhood sexual abuse, poor parental relationships, and early-onset
      incarceration (prior to 21 years of age) were important correlates of serious
      violent crimes. These findings highlight the need for interventions that address
      offenders' prior adult and childhood victimization and suggest that policies for
      reentering violent offenders should encompass an understanding of the broader
      family contexts in which these patterns of maltreatment often occur.

PMID- 23155729
TI  - Evidence for crossmodal interactions across depth on target localisation
      performance in a spatial array.
AB  - Auditory stimuli are known to improve visual target recognition and detection
      when both are presented in the same spatial location. However, most studies have
      focused on crossmodal spatial congruency along the horizontal plane and the
      effects of audio-visual spatial congruency in depth (i.e., along the depth axis)
      are relatively less well understood. In the following experiments we presented a
      visual (face) or auditory (voice) target stimulus in a location on a spatial
      array which was either spatially congruent or incongruent in depth (i.e.,
      positioned directly in front or behind) with a crossmodal stimulus. The
      participant's task was to determine whether a visual (experiments 1 and 3) or
      auditory (experiment 2) target was located in the foreground or background of
      this array. We found that both visual and auditory targets were less accurately
      located when crossmodal stimuli were presented from different, compared to
      congruent, locations in depth. Moreover, this effect was particularly found for
      visual targets located in the periphery, although spatial incongruency affected
      the location of auditory targets across both locations. The relative distance of
      the array to the observer did not seem to modulate this congruency effect
      (experiment 3). Our results add to the growing evidence for multisensory
      influences on search performance and extend these findings to the localisation of
      targets in the depth plane.

PMID- 23155730
TI  - Height perception influenced by texture gradient.
AB  - Three experiments were carried out to examine whether a texture gradient
      influences perception of relative object height. Previous research implicated
      texture cues in judgments of object width, but similar influences have not been
      demonstrated for relative height. In this study, I evaluate a hypothesis that the
      projective ratio of the number of texture elements covered by the objects
      combined with the ratio of the retinal object heights determines percepts of
      relative object height. Density of texture background was varied: four density
      conditions ranged from no-texture to very dense texture. In experiments 1 and 2,
      participants judged the height of comparison bar compared to the standard bar
      positioned on no-texture or textured backgrounds. Results showed relative height
      judgments differed with texture manipulations, consistent with predictions from a
      hypothesised combination of the number of texture elements with retinal height
      (experiment 1), or partially consistent with this hypothesis (experiment 2). In
      experiment 2, variations in the position of a comparison object showed that
      comparisons located far from the horizon were judged more poorly than in other
      positions. In experiment 3 I examined distance perception; relative distance
      judgments were found to be also affected by textured backgrounds. Results are
      discussed in terms of Gibson's relational theory and distance calibration theory.

PMID- 23155731
TI  - Luminance profiles of luminance gradients affect the feeling of dazzling.
AB  - The feeling of dazzling that is evoked by luminance gradients was examined. The
      stimulus consisted of a disk with uniform luminance surrounded by an annulus
      whose luminance was decreased from the inner boundary to the periphery. Three
      luminance profiles (linear, logistic, and inverse logistic) of a surrounding
      luminance ramp were used. The luminance of the disk and the maximum luminance of
      the annulus were also varied. The feeling of dazzling became stronger as the
      luminance of the disk and the maximum luminance of the annulus increased. The
      effect of the maximum luminance of the annulus was greater for the disk with low
      luminance than for that with high luminance. The feeling of dazzling tended to be
      greater for the logistic profile than for the other profiles. However, when the
      luminance of the disk and that at the inner boundary of the annulus were the
      same, the feeling of dazzling for the logistic profile was no stronger than that
      for the linear or the inverse-logistic profile. These results suggest that smooth
      transition from the disk to the annulus for the logistic profile suppresses the
      feeling of dazzling.

PMID- 23155732
TI  - Eye and hand movements during reconstruction of spatial memory.
AB  - Recent behavioural and biological evidence indicates common mechanisms serving
      working memory and attention (e.g., Awh et al, 2006 Neuroscience 139 201-208).
      This study explored the role of spatial attention and visual search in an adapted
      Corsi spatial memory task. Eye movements and touch responses were recorded from
      participants who recalled locations (signalled by colour or shape change) from an
      array presented either simultaneously or sequentially. The time delay between
      target presentation and recall (0, 5, or 10 s) and the number of locations to be
      remembered (2-5) were also manipulated. Analysis of the response phase revealed
      subjects were less accurate (touch data) and fixated longer (eye data) when
      responding to sequentially presented targets suggesting higher cognitive effort.
      Fixation duration on target at recall was also influenced by whether spatial
      location was initially signalled by colour or shape change. Finally, we found
      that the sequence tasks encouraged longer fixations on the signalled targets than
      simultaneous viewing during encoding, but no difference was observed during
      recall. We conclude that the attentional manipulations (colour/shape) mainly
      affected the eye movement parameters, whereas the memory manipulation (sequential
      versus simultaneous, number of items) mainly affected the performance of the hand
      during recall, and thus the latter is more important for ascertaining if an item
      is remembered or forgotten. In summary, the nature of the stimuli that is used
      and how it is presented play key roles in determining subject performance and
      behaviour during spatial memory tasks.

PMID- 23155733
TI  - The minimal time required to process visual information in visual search tasks
      measured by using gaze-contingent visual masking.
AB  - To estimate the minimal time required to process visual information (i.e.,
      "effective acquisition time") during a visual search task, we used a gaze
      contingent visual masking method. In the experiment, an opaque mask that
      restricted the central vision was presented at a current gaze position. We
      manipulated a temporal delay from a gaze shift to mask movement. Participants
      were asked to search for a target letter (T) among distractor letters (L)s as
      quickly as possible under various delays. The results showed that the reaction
      times and search rate decreased when the delay was increased. When the delay was
      longer than 50 ms, the reaction times and search rate reached a plateau. These
      results indicate that the effective acquisition time during the visual search
      task used in the study is equal to or less than 50 ms. The present study
      indicates that the gaze-contingent visual masking method used is useful for
      revealing the effective acquisition time.

PMID- 23155734
TI  - Subjective contours along truncated letters.
AB  - The truncation of upper-case words can result in a subjective contour along the
      truncated ends of the letters. We explored this effect in two experiments
      designed to tease apart the processes responsible: in particular, the possible
      role of letter recognition. Such a role would indicate an unprecedented
      involvement of "high-level vision" in the genesis of subjective contours. In
      experiment 1, we confirmed the basic effect of word truncation in eliciting a
      subjective contour, using only letters where truncation does not eliminate any
      critical features. In experiment 2, we showed that the effect is not confined to
      words/letters but is equally strong for controlled non-letter stimuli that, like
      words, have many forms that have an inflection or an intersection near the
      centre. Truncation at one end then introduces proportional imbalance between
      upper and lower sections of the figures. We conclude from the two experiments
      that part of the effect is due to vertical shortening per se and the rest to the
      proportional imbalance introduced by the truncation. The effect of proportional
      imbalance, a novel determinant of subjective contours, may result from experience
      with letters, although the effect is not "high level" in requiring the
      recognition of specific letters.

PMID- 23155735
TI  - Evidence for a size underestimation of upright faces.
AB  - We quantitatively examined the difference in perceived size between upright and
      inverted faces using the method of constant stimuli. The stimuli included eight
      face images modified from two cartoon faces produced by Kitaoka (2007,
      http://www.psy.ritsumei.ac.jp/-akitaoka/kao-e.html and 2008, Cognitive Psychology
      5 177-185) and six photographic faces, including a photographic face used by
      Thompson (2010, http://illusionncontest.neuralcorrelate.com/2010/the-fat-face
      thin-fft-ilusion/). Experiment 1 showed that an upright face and outline were
      perceived to be significantly smaller than an inverted face and outline,
      respectively. Moreover, the amount of the size underestimation in the face
      stimulus condition was significantly larger than that in the outline stimulus
      condition. Experiment 2 showed that an upright face was perceived to be
      significantly smaller than 90 degrees and 270 degrees rotated faces, whereas an
      inverted face was not perceived to be significantly larger than a 90 degrees or
      270 degrees rotated face. Experiment 3 showed that upright faces were perceived
      to be significantly smaller than upright and inverted outlines, whereas inverted
      faces were not perceived to be significantly larger than upright or inverted
      outlines. Experiments 4 and 5 showed that upright photographic faces were also
      perceived to be significantly smaller than inverted photographic faces. These
      results provide quantitative evidence for a size underestimation of upright
      faces.

PMID- 23155736
TI  - Associations between auditory pitch and visual elevation do not depend on
      language: evidence from a remote population.
AB  - Associations between auditory pitch and visual elevation are widespread in many
      languages, and behavioral associations have been extensively documented between
      height and pitch among speakers of those languages. However, it remains unclear
      whether perceptual correspondences between auditory pitch and visual elevation
      inform these linguistic associations, or merely reflect them. We probed this
      cross-modal mapping in members of a remote Kreung hill tribe in northeastern
      Cambodia who do not use spatial language to describe pitch. Participants viewed
      shapes rising or falling in space while hearing sounds either rising or falling
      in pitch, and reported on the auditory change. Associations between pitch and
      vertical position in the Kreung were similar to those demonstrated in populations
      where pitch is described in terms of spatial height. These results suggest that
      associations between visual elevation and auditory pitch can arise independently
      of language. Thus, widespread linguistic associations between pitch and elevation
      may reflect universally predisposed perceptual correspondences.

PMID- 23155737
TI  - Visual influence on haptic torque perception.
AB  - The brain receives input from multiple sensory modalities simultaneously, yet we
      experience the outside world as a single integrated percept. This integration
      process must overcome instances where perceptual information conflicts across
      sensory modalities. Under such conflicts, the relative weighting of information
      from each modality typically depends on the given task. For conflicts between
      visual and haptic modalities, visual information has been shown to influence
      haptic judgments of object identity, spatial features (e.g., location, size),
      texture, and heaviness. Here we test a novel instance of haptic-visual conflict
      in the perception of torque. We asked participants to hold a left-right
      unbalanced object while viewing a potentially left-right mirror-reversed image of
      the object. Despite the intuition that the more proximal haptic information
      should dominate the perception of torque, we find that visual information exerts
      substantial influences on torque perception even when participants know that
      visual information is unreliable.

PMID- 23155738
TI  - Specular vision-touch synaesthesia: two reference frames.
AB  - Two subtypes of vision-touch synaesthesia (VTS) have been identified. For
      anatomical VTS, sight of touch on another person elicits synaesthetic tactile
      sensation at the same location on the observer's own body (e.g., viewed touch on
      the left cheek elicits sensation on the observer's left cheek). For specular VTS,
      sight of touch on another person elicits synaesthetic tactile sensation at the
      mirror-reflected location (e.g., viewed touch on the left cheek elicits sensation
      on the observer's right cheek). Here we report two distinctly different patterns
      of sensation within the specular subtype. Both participants experienced
      synaesthetic tactile sensation on their right hand when they viewed
      unidirectional brushstrokes administered to a prosthetic left hand (positioned
      with fingers pointing toward the participant), but the direction of sensation
      matched the viewed touch in a hand-centred (spatial) reference frame for RS and
      in an external (viewer-centred) reference frame for NC. Competing reference
      frames affect how individuals with specular VTS experience synaesthetic tactile
      sensation.

PMID- 23155739
TI  - Emotional sounds influence vertical vection.
AB  - While viewing a large vertically moving sinusoidal luminance grating, the
      perception of upward self-motion (vection) was modulated by positive sounds
      (e.g., a baby's laughter). This may be because positive emotion and the spatial
      metaphor of vertical directions were unified in the mind.

PMID- 23155740
TI  - Interpolation of illusory pain in the human somatosensory system.
AB  - Three coins are lined up with the middle coin at room temperature and flanking
      coins cooled down to 4 degrees C. If digits 2 and 4 are placed on the outer coins
      and digit 3 on the middle coin, the latter also feels cold; a striking example of
      perceptual filling in of temperature. We show that if digits 2 and 4 are placed
      on a thermal grill with alternating hot and cold bars, while digit 3 is placed on
      cardboard, the sensation of pain will also spread to the middle finger.

PMID- 23155741
TI  - A comparison of the capital structures of nonprofit and proprietary health care
      organizations.
AB  - The relative amount of debt used by an organization is an important determination
      of the organization's likelihood of financial problems and its cost of capital.
      This study addresses whether or not there are any differences between proprietary
      and nonprofit health care organizations in terms of capital structure.
      Controlling for profitability, risk, growth, and size, analysis of covariance is
      used to determine whether or not proprietary and nonprofit health care
      organizations use the same amount of leverage in their capital structures. The
      results indicate that there is no difference in the amount of leverage between
      the two institutional types. Although nonprofit and proprietary organizations
      have unique financing mechanisms, these differences do not impact the relative
      amount of debt and equity in their capital structures.

PMID- 23155742
TI  - A comparative analysis of the CVP structure of nonprofit teaching and for-profit
      non-teaching hospitals.
AB  - Due to the market turbulence facing the hospital industry, the financial
      viability of teaching hospitals has been severely threatened. Their missions of
      education, research, and patient care even strengthen this crisis. Therefore, the
      objective of this study is to conduct a comparative analysis of the cost, volume,
      and profit (CVP) structure between large nonprofit urban teaching hospitals and
      small for-profit rural/suburban non-teaching hospitals. The following two
      hypotheses were developed: (1) large nonprofit urban teaching hospitals tend to
      have higher fixed cost, lower variable cost, lower total revenue adjusted by case
      mix index (CMI), and lower return on total assets (ROA); and (2) small for-profit
      rural/suburban non-teaching hospitals tend to have lower fixed cost, higher
      variable cost, higher total revenue adjusted by CMI, and higher ROA. Using 117
      teaching hospitals and 102 non-teaching hospitals selected from the Medicare Cost
      Report database in 2005, the results from multiple regression indicated that
      large nonprofit teaching hospitals located in urban areas are more likely to have
      higher fixed cost and lower variable cost. While such cost structure doesn't
      necessarily affect their total revenue adjusted by CMI, it does lead to a lower
      return on hospitals' total assets. The results support our hypotheses in terms of
      fixed cost percentage, variable cost percentage, and ROA, but not total revenue
      adjusted by CMI. The results suggest that cost structure is significantly
      associated with hospitals' performance. Also, as teaching hospitals' portfolios
      of services and programs increase (e.g., provision of uncompensated care to
      Medicare and Medicaid patients and doing research), it becomes strategically
      necessary and critical to manage the allocation of resources or investments into
      the fixed capital that supports the business.

PMID- 23155743
TI  - The economics of health care quality and medical errors.
AB  - Hospitals have been looking for ways to improve quality and operational
      efficiency and cut costs for nearly three decades, using a variety of quality
      improvement strategies. However, based on recent reports, approximately 200,000
      Americans die from preventable medical errors including facility-acquired
      conditions and millions may experience errors. In 2008, medical errors cost the
      United States $19.5 billion. About 87 percent or $17 billion were directly
      associated with additional medical cost, including: ancillary services,
      prescription drug services, and inpatient and outpatient care, according to a
      study sponsored by the Society for Actuaries and conducted by Milliman in 2010.
      Additional costs of $1.4 billion were attributed to increased mortality rates
      with $1.1 billion or 10 million days of lost productivity from missed work based
      on short-term disability claims. The authors estimate that the economic impact is
      much higher, perhaps nearly $1 trillion annually when quality-adjusted life years
      (QALYs) are applied to those that die. Using the Institute of Medicine's (IOM)
      estimate of 98,000 deaths due to preventable medical errors annually in its 1998
      report, To Err Is Human, and an average of ten lost years of life at $75,000 to
      $100,000 per year, there is a loss of $73.5 billion to $98 billion in QALYs for
      those deaths--conservatively. These numbers are much greater than those we cite
      from studies that explore the direct costs of medical errors. And if the estimate
      of a recent Health Affairs article is correct-preventable death being ten times
      the IOM estimate-the cost is $735 billion to $980 billion. Quality care is less
      expensive care. It is better, more efficient, and by definition, less wasteful.
      It is the right care, at the right time, every time. It should mean that far
      fewer patients are harmed or injured. Obviously, quality care is not being
      delivered consistently throughout U.S. hospitals. Whatever the measure, poor
      quality is costing payers and society a great deal. However, health care leaders
      and professionals are focusing on quality and patient safety in ways they never
      have before because the economics of quality have changed substantially.

PMID- 23155744
TI  - Complicated billing requirements challenge physical therapy industry, creating
      inefficiencies and confusion.
AB  - This article is designed to explain the subtle differences between the
      reimbursement requirements for coverage of physical therapy services in physician
      based settings under the Medicare benefit policy manual chapter 15--covered
      medical and other health services. These billing challenges have a profound
      financial impact on the physical therapy industry. This article includes: (1) a
      general back ground of the reasons surrounding the increased regulations in the
      physical therapy industry; (2) general definitions within the physical therapy
      industry; (3) a discussion of the confusing and complicated bill ing requirements
      for physical therapy services; (4) a discussion of the "incident to" billing
      requirements within the physical therapy billing requirements; (5) an explanation
      of differing rules or policies within the physical therapy billing requirements;
      and (6) a discussion of why these rules regarding physical therapy billing
      requirements are essential to the delivery of quality of care within the physical
      therapy industry.

PMID- 23155745
TI  - Americans with Disability Act: financial aspects of reasonable accommodations and
      undue hardship.
AB  - The Americans with Disability Act (ADA) is a significant piece of discrimination
      legislation that merits ongoing managerial exploration. This civil rights
      legislature indicates that employers are expected to provide reasonable
      accommodations to employees with reported disabilities. The statute also
      indicates that employers can refuse to offer a reasonable accommodation if doing
      so creates an undue hardship on the organization. However, health care managers
      should exercise extreme caution when using undue hardship as a defense against
      providing reasonable accommodations to employees with disabilities. This point
      should be duly noted by health care managers given that studies indicate that
      lawsuits alleging disability discrimination are on the rise. This is unfortunate
      given the costs of reasonable accommodations are typically miniscule.

PMID- 23155746
TI  - A real options approach to clinical faculty salary structure.
AB  - One can use the option theory model originally developed to price financial
      opportunities in security markets to analyze many other economic arrangements
      such as the salary structures of clinical faculty in an academic medical center
      practice plan. If one views the underlying asset to be the portion (labeled
      "salary") of the economic value of the collections made for the care provided
      patients by the physician, then a salary guarantee can be considered a put option
      provided the physician, the guarantee having value to the physician only when the
      actual salary earned is less than the salary guarantee. Similarly, within an
      incentive plan, a salary cap can be thought of as a call option provided to the
      practice plan since a salary cap only has value to the practice plan when a
      physician's earnings exceed the cap. Further, based on analysis of prior
      earnings, the Black-Scholes options pricing model can be used both to price each
      option and to determine a financially neutral balance between a salary guarantee
      and a salary cap by equating the prices of the implied put and call options. We
      suggest that such analysis is superior to empirical methods for setting clinical
      faculty salary structure in the academic practice plan setting.

PMID- 23155747
TI  - [Botulism].
AB  - Botulism is a rare but potentially life-threatening disease caused by Clostridium
      botulinum neurotoxin. In Finland only a few cases have been diagnosed during the
      past ten years but mild cases may be underdiagnosed. The diagnosis of botulism is
      clinical. Patients present with weakness in muscles innervated by the cranial
      nerves. In more severe cases the paralysis gradually progresses in a descending
      order and may affect respiratory muscles leading to mechanical ventilation.
      Routine laboratory tests or radiology are unhelpful in initial diagnostics. A
      practicing physician should administrate botulinum antitoxin immediately when
      food-borne botulism is suspected since it may be life-saving.

PMID- 23155748
TI  - [Liver disease and hemostasis--evaluation of bleeding risk].
AB  - In severe liver disease, simultaneous abnormalities in procoagulant and
      anticoagulant pathways seem to maintain the hemostatic balance, provided that the
      platelet level is sufficient. Common coagulation screening tests such as INR fail
      to measure the concomitant anticoagulant deficiencies and fibrinolytic
      abnormalities, and do not predict bleeding in patients with compensated liver
      disease undergoing invasive procedures. Thus, specific INR cut-off levels and
      prophylactic use of fresh-frozen plasma are discouraged. Volume expansion,
      hemodynamic disruption, endothelial dysfunction, and infections increase the
      bleeding risk. Individualized bleeding risk assessment mandates evaluation of the
      patient's clinical condition and a comprehensive assessment of the hemostatic
      system.

PMID- 23155749
TI  - [Risk of obstetric anal sphincter injury in vaginal births could be reduced].
AB  - Obstetric anal sphincter injury (OASIS) is a well-known, serious complication of
      vaginal delivery that can have serious implications for women's subsequent
      health. The risk factors for OASIS included first vaginal delivery, high
      birthweight, prolonged second stage of birth, and operative vaginal deliveries.
      Manual perineum protection and use of mediolateral or lateral episiotomy
      decreased the risk of OASIS. However, in the order of 99-1000 women must be
      exposed to an episiotomy in vaginal deliveries, and 13-67 in operative vaginal
      deliveries to prevent a single OASIS. The results indicate the value of selective
      use of medio-lateral/lateral episiotomy in spontaneous vaginal iberal use of
      deliveries whereas more I it might be advisable in operative vaginal deliveries.

PMID- 23155750
TI  - [MODY diabetes--a monogenic developmental and functional disturbance of
      pancreatic beta cells].
AB  - MODY (Maturity-Onset Diabetes of the Young) is a group of monogenic disorders
      characterized by autosomally dominantly inherited diabetes or hyperglycemia
      typically detected during adolescence or young adulthood. Usually there is at
      least one person in the family having developed the disease at the age of under
      25 years, and the patients are diagnosed with insufficient insulin response to
      glucose, occasionally also with developmental disturbances of various organs. The
      most common form is GCK-MODY caused by glucokinase mutations, primarily
      manifested as elevated fasting glucose levels, usually without the risk of
      complicating diseases.

PMID- 23155751
TI  - [Cystic kidney disease and diabetes--an underdiagnosed monogenic developmental
      disorder].
AB  - Heterozygous mutations in the TCF2 gene encoding the transcription factor HNF-11
      cause a dominantly inherited developmental disorder that may be associated with
      various dysplastic and cystic lesions of the kidneys and renal insufficiency,
      disorder of pancreatic development and insulin-deficient MODY diabetes, aberrant
      hepatic enzyme levels, gout and genital anomalies. Symptoms and findings vary in
      their degree of severity. When an isolated abnormality is detected, recognition
      of the syndrome is essential in order to diagnose the other organ manifestations.
      Since the mid-2000's, 10 to 20 patients have been diagnosed in Finland.

PMID- 23155752
TI  - [Reconstructive surgery of leg ulceration].
AB  - The great majority of chronic leg ulcers are caused by disturbances of venous and
      arterial circulation in the lower extremities. Diagnostics and treatment of
      ulcers require multiprofessional collaboration. The cornerstone of the treatment
      is conservative treatment intervening in the underlying causes of the ulceration.
      If the ulcer is large or recovery does not take place with appropriate
      conservative therapy, reconstructive surgery may come into question, i.e.
      surgical excision of the ulcer and its covering with a skin graft.

PMID- 23155753
TI  - [Outcome of childhood cancer in Tampere, Finland].
AB  - BACKGROUND: We investigated the outcome of childhood cancer within the Tampere
      University Hospital area, Finland. PATIENTS AND METHODS: We collected the data
      from 291 patients, who were 0 to 16 years of age at the time of cancer diagnosis
      in 1997 to 2006. The largest diagnosis groups were leukemias, malignant tumors of
      the central nervous system, and lymphomas. RESULTS: Altogether 83% of the
      patients were alive and at least under long-term remission at the time of the
      study. CONCLUSIONS: Outcome of childhood cancer in Tampere University Hospital
      area is in line with international results.

PMID- 23155754
TI  - [Increased risk of tromboembolic complication in patients with inflammatory bowel
      disease].
AB  - Tromboembolic complications are 2-4-fold more likely in patients with
      inflammatory bowel disease (IBD) than in healthy individuals; active IBD may
      increase the relative risk even 15-fold. Deep vein thrombosis and pulmonary
      embolism are the most common involvements, but also atypical forms occur. We
      describe such uncommon thrombotic manifestations in two IBD patients: one had
      mesenterial vein and the other cavernoid sinus thrombosis. The risk of thrombotic
      complications should be estimated individually, and prophylactic management with
      low molecular weight heparin should be considered in hospitalized IBD patients.

PMID- 23155755
TI  - ["With all measures...". Appeal proceedings and political specialty disputes
      about orthopedics at the Berlin University and the Charite during the time of the
      Kaiser Empire, the Weimar Republic and national socialism].
AB  - In 1934 the NSDAP University-Commission forced the president of the German
      Society of Surgery and the chairman of the German Orthopaedic Society to sign a
      reconciliation agreement. First of all, orthopaedists and surgeons were ordered
      to refrain from attacking each other in public. In the future, in the event of
      any complaints, they were to address the 'Reichsarztefuhrung' at the Ministry of
      the Interior. On the basis of papers and documents from the archives of the
      medical faculty, the East German Ministry for State Security and the former
      Berlin Document Centre, this article describes the history of the emerging
      medical specialty orthopaedics at the University of Berlin and the Charite
      hospital. It covers a period from 1890 through 1945 and focuses on the varying
      relations between political authorities, medical associations and the faculty.
      The main attention is given to ethical and economic disputes and to the way in
      which professors for orthopaedics were appointed. The two pioneers of orthopaedic
      surgery, Julius Wolff and Albert Hoffa had to overcome less resistance than their
      successors Georg Joachimsthal and Hermann Gocht. Gocht's fate changed, when the
      NSDAP took Power. As a protege of the regime he represented the medical faculty
      during the period of political cleansing. In 1937 the appointment of the
      orthopaedist Lothar Kreuz as a full member of the medical faculty was no longer a
      university matter anymore. His appointment was negotiated entirely within the
      organisations of the NSDAP. Politically approved, Kreuz served as dean of the
      medical faculty and later was to be the last rector of the University of Berlin.
      For the first time, this article documents the connections between Kreuz, the
      paramilitary squadron of the party SS, and key political figures.

PMID- 23155756
TI  - [On the astrology and computation in the 12th century: new unpublished
      manuscripts ].
AB  - This article examines three so far unknown lemmatic commentaries on computus and
      on astrolabe topics, which are to be found in MS Stuttgart, Wurttembergische
      Landesbibliothek, Cod. math. 4 degrees 33 (second half of the twelfth-century).
      The commentaries are on the 'Compotus' by Gerlandus, on the 'De mensura
      astrolabii' by Hermann of Reichenau, and on the 'De utilitatibus astrolabii',
      which is sometimes attributed to Gerbert of Aurillac. No commentaries on the
      respective treatises have previously been identified as such. The commentaries of
      the Stuttgart manuscript are of special interest in that they allow us to
      understand how a twelfth-century scholar read works on computus and the
      astrolabe, namely works that date back to the eleventh century. Their author
      remains anonymous, but in all probability he wrote his commentary on the
      'Compotus' by Gerlandus either in 1143 or in 1150. An appendix to the article
      includes transcriptions of the introductory texts on the computus and on the
      astrolabe as well as the beginnings of the commentaries.

PMID- 23155757
TI  - [Reference relationships between human and animal in Hildegard von Bingen].
AB  - In "De animalibus", the 7th book in the "Liber simplicis medicinae", Hildegard
      von Bingen describes the characteristics of four-footed land animals. Some of
      these have a special relationship with humans in that they embody moral
      qualities. An explanation for this is already given in the preface, which states
      that human intelligence recognizes these qualities, declaring that "You are this
      or that sort of creature". Since the relationship that animals have with nature
      shares a degree of similarity with that of man's, they can be regarded as
      symbolic representatives for particular human traits and characteristics. The
      article at hand presents Hildegard von Bingen's descriptions of the monkey, the
      lion, the bear, the rabbit, the dog, the cat, the wolf, the lynx, and the donkey.
      While the monkey just mimics man's behaviour and is imperfect in both settings,
      the lion embodies will power. The bear on the other hand stands for unbridled
      sexual desire, while in the rabbit the gentleness of a sheep is united with the
      bounce of a deer. The lynx is regarded as hedonistic, the donkey as stupid, and
      the wolf as surrounded by dangerous sylphs. In Hildegard's depictions, exotic and
      native animal species display rather extraordinary behavioural traits, and the
      medieval Christian world view of the author conveys unexpected relationships
      between humans and animals. In addition to empirical observation and experience,
      Hildegard also relies on folkloristic beliefs and magical practices related to
      explanatory models of her time. She allows largely unknown sources into her
      animal lore but never strays from her ultimate goal of having it serve to
      instruct people. In doing so, Hildegard removed herself far from the common
      tradition of medieval animal portraits.

PMID- 23155758
TI  - K. 263+10934, A tablet with recipes against the abnormal flow of a woman's blood.

PMID- 23155759
TI  - ["Could not therefore the earth globe also be a large tourmaline?" A crystal,
      Lichtenberg and the polarity discussion before 1800].
AB  - This paper focuses on the debate on one particular phenomenon of the research
      into electrical charge distribution prior to 1800: the description and
      interpretation of polarities observed on the tourmaline. We show that in the
      second half of the eighteenth century this crystal became a model to distinguish
      and categorize different qualities of charges (electric and magnetic fluids). It
      will become clear that the polarity detected on the tourmaline became a key
      concept for eighteenth century natural philosophy, which relied on analogizing
      operations. We illustrate this concentrating on Lichtenbergs first lecture at the
      Gottingen academy of science in 1778. Thus the concept of polarity is already a
      central ordering category before the beginnings of the speculative enterprise of
      idealistic Naturphilosophy. Consequently, the physicist Johann Wilhelm Ritter,
      who can be positioned in that context, consciously adheres to the experimental
      research tradition of polarities portrayed in this paper.

PMID- 23155760
TI  - A hybrid approach to gene ranking using gene relation networks derived from
      literature for the identification of disease gene markers.
AB  - For the identification of gene markers involved in diseases, microarray
      expression profiles have been widely used to prioritize genes. In this paper, we
      propose a novel approach to gene ranking that employs gene relation network
      derived from literature along with microarray expression scores to calculate
      ranking statistics of individual genes. In particular, the gene relation network
      is constructed from literature by applying syntactic analysis and co-occurrence
      method in a hybrid manner. For evaluation, the proposed method was tested with
      publicly available prostate cancer data. The result shows that our method is
      superior to other existing approaches.

PMID- 23155761
TI  - Tri-mean-based statistical differential gene expression detection.
AB  - Based on the assumption that only a subset of disease group has differential gene
      expression, traditional detection of differentially expressed genes is under the
      constraint that cancer genes are up- or down-regulated in all disease samples
      compared with normal samples. However, in 2005, Tomlins assumed and discussed the
      situation that only a subset of disease samples would be activated, which are
      often referred to as outliers.

PMID- 23155762
TI  - MicroRNAfold: pre-microRNA secondary structure prediction based on modified NCM
      model with thermodynamics-based scoring strategy.
AB  - An accurate prediction of the pre-microRNA secondary structure is important in
      miRNA informatics. Based on a recently proposed model, nucleotide cyclic motifs
      (NCM), to predict RNA secondary structure, we propose and implement a Modified
      NCM (MNCM) model with a physics-based scoring strategy to tackle the problem of
      pre-microRNA folding. Our microRNAfold is implemented using a global optimal
      algorithm based on the bottom-up local optimal solutions. Our experimental
      results show that microRNAfold outperforms the current leading prediction tools
      in terms of True Negative rate, False Negative rate, Specificity, and Matthews
      coefficient ratio.

PMID- 23155763
TI  - Genome-wide identification and evolutionary analysis of B7-H3.
AB  - B7-H3 is an immune co-stimulatory molecule of the B7 family that contains a set
      of immunoglobulin-V (IgV) and immunoglobulin-C (IgC) domains. To explore the
      evolutionary process of B7-H3 gene, we conducted a genome-wide structure and
      phylogenetic analysis of B7-H3 genes in currently sequenced genomes. On the basis
      of the available data, 17 mammalian B7-H3 genes were predicted to have tandemly
      duplicated 4Ig domains. The analysis of gene structure and phylogenesis reveal
      that these 4IgB7-H3 genes resulted from domain duplication. Nevertheless, no
      difference in function has been observed between the two isoforms. It is more
      likely that domain duplication in 4IgB7-H3 leads to functional redundancy.

PMID- 23155764
TI  - A new clustering approach for learning transcriptional modules.
AB  - In modern biology, we had an explosion of genomic data from multiple sources,
      like measurements of RNA levels, gene sequences, annotations or interaction data.
      These heterogeneous data provide important information that should be integrated
      through suitable learning methods aimed at elucidating regulatory networks. We
      propose an iterative relational clustering procedure for finding modules of co
      regulated genes. This approach integrates information concerning known
      Transcription Factors (TFs)--gene interactions with gene expression data to find
      clusters of genes that share a common regulatory program. The results obtained on
      two well-known gene expression data sets from Saccharomyces cerevisiae are shown.

PMID- 23155765
TI  - Select your SNPs (SYSNPs): a web tool for automatic and massive selection of
      SNPs.
AB  - Association studies are the choice approach in the discovery of the genomic basis
      of complex traits. To carry out such analysis, researchers frequently need to (1)
      select optimally informative sets of Single Nucleotide Polymorphisms (SNPs) in
      candidate regions and (2) annotate the results of associations found by means of
      genome-wide SNP arrays. These are complex tasks, since many criteria have to be
      considered, including the SNPs' functional properties, technological information
      and haplotype frequencies in given populations. SYSNPs implements algorithms that
      allow for efficient and simultaneous consideration of all the relevant criteria
      to obtain sets of SNPs that properly cover arbitrarily large lists of genes or
      genomic regions. Complementarily, SYSNPs allows for comprehensive functional
      annotation of SNPs linked to any given marker SNP. SYSNPs dramatically reduces
      the effort needed for SNP selection from days of searching various databases to a
      few minutes using a simple browser.

PMID- 23155766
TI  - Hybrid softcomputing model for lesion identification and information combination:
      some case studies.
AB  - Authors present segmentation and information combination of section of human
      brain images. Improved hybrid algorithm is presented for clustering, which
      integrates the concept of Rough sets, Fuzzy sets incorporated with probabilistic
      as well as possibilistic memberships. The segmented images are fused using
      wavelet and curvelet based techniques. Lower and upper approximations of Rough
      sets handle uncertainty, vagueness, and incompleteness in class definition. To
      accelerate the segmentation process, the RFPCM has been equipped with membership
      suppression mechanism, which creates competition among clusters to speed-up the
      clustering process using MR T1 and MR T2 images of section of human brain.

PMID- 23155767
TI  - Agent-based model of macrophage action on endocrine pancreas.
AB  - This paper proposes an agent-based model of the action of macrophages on the beta
      cells of the endocrine pancreas. The aim of this model is to simulate the
      processes of beta cell proliferation and apoptosis and also the process of
      phagocytosis of cell debris by macrophages, all of which are related to the onset
      of the autoimmune response in type 1 diabetes. We have used data from the
      scientific literature to design the model. The results show that the model
      obtains good approximations to real processes and could be used to shed light on
      some open questions concerning such processes.

PMID- 23155768
TI  - An integrative approach for codon repeats evolutionary analyses.
AB  - The relationship between genome characteristics and several human diseases has
      been a central research goal in genomics. Many studies have shown that specific
      gene patterns, such as amino acid repetitions, are associated with human
      diseases. However, several open questions still remain, such as, how these tandem
      repeats appeared in the evolutionary path or how they have evolved in orthologous
      genes of related organisms. In this paper, we present a computational solution
      that facilitates comparative studies of orthologous genes from various organisms.
      The application uses various web services to gather gene sequence information,
      local algorithms for tandem repeats identification and similarity measures for
      gene clustering.

PMID- 23155769
TI  - An integrated computational environment for elementary modes analysis of
      biochemical networks.
AB  - Elementary flux modes (EFMs) have been claimed as one of the most promising
      approaches for pathway analysis. These are a set of vectors that emerge from the
      stoichiometric matrix of a biochemical network through the use of convex
      analysis. The computation of all EFMs of a given network is an NP-hard problem
      and existing algorithms do not scale well. Moreover, the analysis of results is
      difficult given the thousands or millions of possible modes generated. In this
      work, we propose a new plug-in, running on top of the OptFlux Metabolic
      Engineering workbench (Rocha et al., 2010), whose aims are to ease the analysis
      of these results and explore synergies among EFM analysis, phenotype simulation
      and strain optimisation. Two case studies are shown to illustrate the
      capabilities of the proposed tool.

PMID- 23155770
TI  - A comparative-based phylogenetic study in the evolution of 16S rRNA and rad a
      genes in Archaea.
AB  - Archaea are ubiquitous in their presence and abundant not only in extreme
      environments, but also in soil, oceans and freshwater, where they may fulfil a
      key role in the biogeochemical cycles of the earth. The identification of
      archaeal genomic signatures elucidates us a measure of distinctiveness of Archaea
      as a coherent group, although these signatures can differ according to the degree
      of stringency. The 16S rRNA and the Rad A genes are highly conserved in living
      organisms and are very useful for the phylogenetic analysis. Phylogenetic trees
      are constructed using the molecular evolutionary genetics analysis (MEGA) tool by
      neighbour joining (NJ) method and repeated bootstrapping for 5000 times was
      performed. The two trees were then compared using the Compare2trees and
      statistically analysed using the MEGA tool. The two phylogenetic trees show a
      similarity of 54.9%. In both the trees, the taxon Thaumarchaeota shows a high
      level of variance. The species Cenarchaeum symbiosum A shows a high level of
      similarity with the sequences of higher organisms (Euryarcheota-eukaryota), which
      shows that it has branched away to higher organisms from a closely related
      Protozoa, Eubacteria ancestor.

PMID- 23155771
TI  - Mining poly-regions in DNA.
AB  - We study the problem of mining poly-regions in DNA. A poly-region is defined as a
      bursty DNA area, i.e., area of elevated frequency of a DNA pattern. We introduce
      a general formulation that covers a range of meaningful types of poly-regions and
      develop three efficient detection methods. The first applies recursive
      segmentation and is entropy-based. The second uses a set of sliding windows that
      summarize each sequence segment using several statistics. Finally, the third
      employs a technique based on majority vote. The proposed algorithms are tested on
      DNA sequences of four different organisms in terms of recall and runtime.

PMID- 23155772
TI  - Semi-supervised clustering algorithm for haplotype assembly problem based on MEC
      model.
AB  - Haplotype assembly is to infer a pair of haplotypes from localized polymorphism
      data. In this paper, a semi-supervised clustering algorithm-SSK (semi-supervised
      K-means) is proposed for it, which, to our knowledge, is the first semi
      supervised clustering method for it. In SSK, some positive information is firstly
      extracted. The information is then used to help k-means to cluster all SNP
      fragments into two sets from which two haplotypes can be reconstructed. The
      performance of SSK is tested on both real data and simulated data. The results
      show that it outperforms several state-of-the-art algorithms on minimum error
      correction (MEC) model.

PMID- 23155773
TI  - Extracting epidemiologic exposure and outcome terms from literature using machine
      learning approaches.
AB  - Much epidemiologic information resides in literature, which is not in a
      computable format. To extract information and build knowledge bases of
      epidemiologic studies, we developed a system to extract noun phrases about
      epidemiologic exposures and outcomes. The system consists of two components: a
      natural language processing (NLP) engine; a machine learning (ML) based
      classifier. Four ML algorithms were applied and compared over different feature
      sets. To evaluate the performance of the system, we manually constructed an
      annotated dataset. The system achieved the highest F-measure of 82.0% for
      extracting exposure terms, and 70% for extracting outcome terms.

PMID- 23155774
TI  - Data mining for high throughput data from genome-wide association studies.

PMID- 23155775
TI  - Support vector machines with L1 penalty for detecting gene-gene interactions.
AB  - Interactions among genetic variants are likely to affect risk for human complex
      diseases, and their identification should increase the power to detect disease
      associated variants and elucidate biological pathways underlying diseases. We
      propose a two-stage approach: model selection with support vector machines
      identifies the most promising single nucleotide polymorphisms and interactions;
      logistic regression ensures a valid type I error by excluding non-significant
      candidates after Bonferroni correction. Simulation studies for case-control data
      suggest that our method powerfully detects gene-gene interactions. We analyze a
      published genome-wide case-control dataset, where our method successfully
      identifies an interaction term, which was missed in previous studies.

PMID- 23155776
TI  - cuGWAM: Genome-wide association multifactor dimensionality reduction using CUDA
      enabled high-performance graphics processing unit.
AB  - Multifactor dimensionality reduction (MDR) method has been widely applied to
      detect gene-gene interactions that are well recognized as playing an important
      role in understanding complex traits. However, because of an exhaustive analysis
      of MDR, the current MDR software has some limitations to be extended to the
      genome-wide association studies (GWAS) with a large number of genetic markers up
      to approximately 1 million. To overcome this computational problem, we developed
      CUDA (Compute Unified Device Architecture) based genome-wide association MDR
      (cuGWAM) software using efficient hardware accelerators, cuGWAM has better
      performance than CPU-based MDR methods and other GPU-based methods.

PMID- 23155777
TI  - Multilocus association analysis under polygenic models.
AB  - For each variant in a genome-wide association study, the risk allele is the one
      with an odds ratio greater than 1. For a given set of variants, the number of
      risk alleles in cases minus that in controls is evaluated and a p-value is
      obtained for this difference. Successive sums of these differences over the best
      2, 3, etc. variants and associated p-values are obtained. The smallest such p
      value is our genome-wide test statistic, for which an empirical significance
      level is obtained by permutation analysis. Applied to disease datasets, our
      approach furnishes significant results even with little single-locus effects.

PMID- 23155778
TI  - Unbalanced sample size effect on genome-wide population differentiation studies.
AB  - The fixation index (F(ST)) is one of the most widely used measurements of genetic
      distance between populations. The data set from the international HapMap project
      has been served as a reference data set for population differentiation studies.
      F(ST) is commonly used in order to compare the sample data with HapMap data. In
      this study, however, we show that the use of F(ST) without consideration of
      sample sizes may mislead the result. In particular, we first demonstrate that
      F(ST) suffers from imbalance of sample sizes through simulation studies and
      through the analysis of a large scale Korean genome-wide association data. Then,
      we propose a modified version of F(ST) which is shown to be more robust to
      imbalance of sample size. In addition, the chi-square test commonly used for
      homogeneity test is shown to perform similarly to the modified version of F(ST).

PMID- 23155779
TI  - Pattern discovery of multivariate phenotypes by association rule mining and its
      scheme for genome-wide association studies.
AB  - Genome-wide association studies (GWAS) have served crucial roles in investigating
      disease susceptible loci for single traits. On the other hand, GWAS have been
      limited in measuring genetic risk factors for multivariate phenotypes from
      pleiotropic genetic effects of genetic loci. This work reports a data mining
      approach to discover patterns of multivariate phenotypes expressed as association
      rules, and presents an analytical scheme for GWAS of those newly defined
      multivariate phenotypes. We identified 13 SNPs for four genes (CSMD1, NFE2L1,
      CBX1, and SKAP1) associated with a new multivariate phenotype defined as low
      levels of low density lipoprotein cholesterol (LDL-C < or = 100 mg/dl) and high
      levels of triglycerides (TG > or = 180 mg/dl). Compared with a traditional
      approach to GWAS, the use of discovered multivariate phenotypes can be
      advantageous in identifying pleiotropic genetic risk factors, which may have a
      common etiological role for the multivariate phenotypes.

PMID- 23155780
TI  - Selecting SNPs for pharmacogenomic association study.
AB  - SNP genotyping device is an essential tool in the upcoming era ofpersonal genome
      and personalised medicine. Human genome has more than 10 million SNPs whereas
      conventional SNP genotyping device can only hold 1 million SNPs. Thus,
      intelligent SNP contents selection is required to maximise the value of SNP
      genotyping device. Here, we developed a new selection algorithm and applied this
      method to design genotyping contents for cancerand pharmacogenomic association
      study. This approach significantly increased the product value when compared with
      contents of competitive SNP genotyping product.

PMID- 23155781
TI  - A 2-phased approach for detecting multiple loci associations with traits.
AB  - The recent advance in SNP genotyping has made a significant contribution to
      reduction of the costs for large-scale genotyping. The development also has
      dramatically increased the size of the SNP genotype data. The increase in the
      volume of the data, however, has posed a huge obstacle to the conventional
      analysis techniques that are typically vulnerable to the high-dimensionality
      problem. To address the issue, we propose a method that exploits two well-tested
      models: the document-term model and the transaction analysis model. The proposed
      method consists of two phases. In the first phase, we reduce the dimensions of
      the SNP genotype data by extracting significant SNPs through transformation of
      the data in lieu of the document-term model. In the second phase, we discover the
      association rules that signify the relations between the SNPs and the traits,
      through the application of transactional analysis in the reduced-dimension
      genotype data. We validated the discovered rules through literature survey.
      Experiments were also carried out using the HGDP panel data provided by the
      Foundation Jean Dausset-CEPH, which prove the validity of our new method for
      identifying appropriate dimensional reduction and associations of multiple SNPs
      and traits. This paper is an extended version of our workshop paper presented in
      the 2010 International Workshop on Data Mining for High Throughput Data from
      Genome-Wide Association Studies.

PMID- 23155782
TI  - Predicting linear B-cell epitopes by using sequence-derived structural and
      physicochemical features.
AB  - The identification of linear B-cell epitopes is important for developing epitope
      based vaccines. Recently, machine learning techniques have been used in the
      epitope prediction, but the existing encoding schemes usually neglected valuable
      discriminative information. In this paper, we proposed a novel encoding scheme
      which combines several groups of sequence-derived structural and physicochemical
      features, and support vector machine was used to construct the prediction models.
      When applied to the benchmark dataset, our proposed method demonstrated better
      results than benchmark methods. Moreover, the study indicated incorporating more
      discriminative features may contribute to the higher prediction performance.

PMID- 23155783
TI  - [Transgenerational psychotraumatology].

PMID- 23155784
TI  - [Intergenerational transmission of trauma--empirical research and family dynamics
      approach].
AB  - A tendency to pass on traumatic experiences from one generation to the next can
      be observed in family systems. This continuity manifests itself very differently,
      e. g. in posttraumatic stress disorders, anxiety disorders, mood disorders,
      aggressive behavior, social withdrawal or health risk behaviors in the second or
      third generation. Besides physiological mechanisms (e. g. levels of cortisol)
      psychosocial "mediators" as attachment security, emotional regulation and
      availability, parenting style as well as family dynamic processes like family
      secrets, communication deviances and resulting disturbances of mentalization,
      disturbances of interpersonal boundaries, conflicts of loyalty and delegation are
      of relevance. A case example and considerations of resilience processes are given
      as well.

PMID- 23155785
TI  - [Burden and capability of damaged parents--how refugee children can grow in
      exile].
AB  - In trauma, dialectical tension arises between the inner perspective of the
      traumatized subject and the outside perspective (objective situation), between
      environmental stress and the subjective attribution of meaning, as well as
      between experience and behaviour. The traumatic process--the subject's endeavour
      to comprehend the overwhelming, often inconceivable experience and integrate it
      into its concepts of self and world--is understood against the backdrop of these
      interacting dimensions. The process phases "emerge from each other, run parallel,
      and permeate each other" (Fischer u. Riedesser, 2003). Problems that arise in the
      aftermath of trauma are rarely overcome by the victims alone. Attempts to process
      and self-heal have a social dimension, and family members are affected by war,
      persecution and flight in individual, varying ways. The impacts of violence
      experienced by parents from different crisis regions are examined in case studies
      with regard to the psychological development of indirectly impacted children
      growing up in exile.

PMID- 23155786
TI  - [The transgenerational transmission of traumatic experiences of the Second World
      War over three generations--a psychoanalytical perspective].
AB  - The paper presents some reflections on the transgenerational transmission of
      traumatic experiences of war and in particular bombing during Second World War.
      These theoretical considerations are based on a case study (family interview)
      deriving from the research project "Kriegskindheit im Hamburger Feuersturm"
      additionally illustrated and complemented with impressions based on interviews
      with three generations in context of the project.

PMID- 23155788
TI  - Acute spinal cord injury - the unchanged challenges!

PMID- 23155787
TI  - ["Suddenly I was all alone": traumatic experiences of a 12 year old girl during
      the "Operation Gomorrha" and its transmission over three generations].
AB  - Air strikes on Hamburg in 1943 ("Operation Gomorrha") were a historical turning
      point and had a deep impact on both cityscape and history of Hamburg. Little is
      known about intraindividual and transgenerational consequences as well as its
      interaction with societal and historical processes. Aiming at closing this gap
      interviews with witnesses, their children and grandchildren, as well as the whole
      family, were conducted in the context of an interdisciplinary research project.
      Based on the example of an interview with a at the time of the "Operation
      Gomorrha" eleven years old witness, her daughter, and grandson the biographical
      localisation of war experiences and transgenerational transmission will be
      explained and discussed.

PMID- 23155789
TI  - Acute spinal cord injury: managing at the site of impact and addressing reality
      gap.

PMID- 23155790
TI  - A physicians' approach to a case of acute spinal cord injury.

PMID- 23155791
TI  - Pharmacological management of acute spinal cord injury.

PMID- 23155792
TI  - Operative management of spinal injuries.

PMID- 23155793
TI  - Rehabilitation for spinal cord-injured patients--Looking beyond bladder, bowel
      and bed sores.

PMID- 23155794
TI  - Stem cell therapy in spinal cord injuries: current concepts.
AB  - The list of experimental therapies that have been developed in animal models to
      improve functional outcomes after spinal cord injury is extensive. Though
      preclinical trials have shown a good potential for cellular therapies in spinal
      cord injury, there is no documentary proof as of now that any form of cellular
      therapy definitely improves outcome in management of human spinal cord injury.
      The adverse effects of many such therapies are well-documented. There is a need
      to conduct proper clinical trials. Some early-stage spinal cord injury clinical
      trials have recently been done and some have been started. However, some
      experimental therapies have been introduced into clinical practice without a
      clinical trial being completed. Undue hype by the media and claims by
      professionals have a profound psychological effect on the spinal cord injured and
      interferes in their rehabilitation. While we know that the future holds a good
      promise, this should not prevent patients from aggressively pursuing
      rehabilitation since we are not sure when a clinical breakthrough will be
      achieved.

PMID- 23155795
TI  - Dyspepsia.

PMID- 23155796
TI  - Functional dyspepsia: the Indian scenario.

PMID- 23155797
TI  - Epidemiology of functional dyspepsia.
AB  - Functional dyspepsia (FD) is the most common cause of dyspeptic symptoms. It
      refers to a heterogeneous group of symptoms located in the upper abdomen. The
      prevalence of dyspepsia is variable in different populations and is related to
      the different definitions of dyspepsia as inclusion criterias, variation in
      survey population and environmental factors. Epidemiologically some risk factors
      have been identified and underlying psychological disturbances have been shown to
      be important factors in FD. Age and ethnicity do not appear to be predictive of
      dyspepsia. A majority of patients suffering from significant levels of abdominal
      pain that interrupt daily activities and treatment remains unsatisfactory in this
      chronic condition.

PMID- 23155798
TI  - Non-ulcer dyspepsia.

PMID- 23155799
TI  - Natural history of functional dyspepsia.

PMID- 23155800
TI  - Etiopathogenesis of functional dyspepsia.

PMID- 23155801
TI  - Clinical features of functional dyspepsia.

PMID- 23155802
TI  - Differential diagnosis in functional dyspepsia.

PMID- 23155803
TI  - Management of functional dyspepsia.

PMID- 23155804
TI  - Future directions in functional dyspepsia.

PMID- 23155805
TI  - India needs a national COPD prevention and control programme.

PMID- 23155806
TI  - Newer therapies for chronic obstructive pulmona disease.

PMID- 23155807
TI  - COPD: the unrecognized epidemic in India.

PMID- 23155808
TI  - Risk factors and pathophysiology of chronic obstructive pulmonary disease (COPD).

PMID- 23155809
TI  - Spirometry in chronic obstructive lung disease (COPD).

PMID- 23155810
TI  - Management of chronic stable COPD.

PMID- 23155811
TI  - Treatment of acute exacerbation of COPD.

PMID- 23155812
TI  - Systemic manifestations of COPD.

PMID- 23155813
TI  - Pulmonary rehabilitation in COPD.

PMID- 23155814
TI  - Smoking cessation programs and other preventive strategies for chronic
      obstructive pulmonary disease.

PMID- 23155815
TI  - Community acquired pneumonia.

PMID- 23155816
TI  - Epidemiology of community acquired pneumonia.

PMID- 23155817
TI  - Pathophysiology of community acquired pneumonia.

PMID- 23155818
TI  - Community acquired pneumonia: clinical manifestations.

PMID- 23155819
TI  - Investigations for pneumonia.

PMID- 23155820
TI  - Diagnosis of community acquired pneumonia.

PMID- 23155821
TI  - Management of community acquired pneumonia.

PMID- 23155822
TI  - Pneumonia: review of guidelines.

PMID- 23155823
TI  - Role of vaccines.

PMID- 23155824
TI  - Community health nursing.

PMID- 23155825
TI  - Preserving health in the Marcellus region.
AB  - Community health nurses (CHNs) have an opportunity and responsibility to address
      potential environmental health issues related to shale drilling, even in the face
      of scientific uncertainty. Potential health impacts to air and water quality
      related to shale drilling are addressed within the context of the CHNs role of
      educator, case finder, advocate and researcher. Since 2005, an estimated 5,500
      unconventional natural gas wells have been drilled in Pennsylvania's Marcellus
      Shale (Pennsylvania Department of Environmental Protection [PA DEP], n.d.),
      resulting in tremendous controversy throughout the state regarding impacts to
      human health and the environment. Although there are numerous anecdotal reports
      of illnesses in humans and animals living in drilling areas, there is a notable
      lack of peer-reviewed research on the impacts. Research efforts are underway to
      study these issues, including a proposed retrospective study of hospital and
      clinic data by Geisinger Health System's Weis Center for Research (Begos, 2012).
      However, CHNs have the opportunity and the responsibility to help address
      potential environmental health issues related to shale drilling, even in the face
      of scientific uncertainty. This responsibility is highlighted by the American
      Nurses Association's (ANA) (2003, p. 2) adoption of the Precautionary Principle,
      which states that "when an activity raises threats of harm to human health or the
      environment, precautionary measures should be taken even if some cause and effect
      relationships are not fully established scientifically." CHN practice includes
      the promotion and preservation of health, and the prevention of disease, as well
      as assisting people in their response to illness (Maurer & Smith, 2009). In
      Pennsylvania's Marcellus Shale regions, CHNs must assume the critical nursing
      roles of educator, case finder, advocate and researcher when addressing the
      health needs in shale drilling communities. Unfortunately, CHNs practicing within
      these regions may feel unprepared to take on these roles related to
      unconventional gas extraction. The following discusses these CHN roles in the
      context of environmental health impacts of shale drilling on air and water
      quality.

PMID- 23155826
TI  - Leading the profession: James Ballinghoff, RN, MSN, MBA, NEA-BC.

PMID- 23155827
TI  - Nurse collaboration impacts end of life care.

PMID- 23155828
TI  - Nurse-to-Nurse communication in home health.

PMID- 23155829
TI  - Changes coming in ANCC advanced practice certification.

PMID- 23155830
TI  - Things to know about choosing a nursing school.

PMID- 23155831
TI  - Running for elective office: a different form of nursing advocacy.

PMID- 23155832
TI  - Are we all under-achievers?

PMID- 23155833
TI  - FAQs on continuing education (CE) requirements for registered nurses, licensed
      practical nurses, dialysis technicians, community health workers and medication
      aides in Ohio.

PMID- 23155834
TI  - Novice to expert: clinical ladder programs as a recruitment and retention tool.

PMID- 23155835
TI  - If you're not moving, you're standing still.

PMID- 23155836
TI  - Addressing the Affordable Care Act.

PMID- 23155837
TI  - How old is old?

PMID- 23155838
TI  - Health care and behavioral change.

PMID- 23155839
TI  - Lost in transition.

PMID- 23155840
TI  - Common medical conditions in elderly dental patients. Part one: cardiovascular
      implications and management.

PMID- 23155841
TI  - Reading...between the lines.

PMID- 23155842
TI  - Question: In females being treated with antibiotics, is probiotic use effective
      in reducing the incidence of vulvovaginal candidiasis?

PMID- 23155843
TI  - Referral pattern for vaginal mesh and graft complications to the University of
      Oklahoma Pelvic and Bladder Health Clinic.
AB  - OBJECTIVE: To evaluate the referral pattern to a tertiary care center for vaginal
      mesh complications following surgeries for pelvic organ support defect. METHODS:
      This was a retrospective review of women presenting to our clinic for
      complications of vaginal mesh. RESULTS: One hundred thirty three patients were
      included in the study. The median age was 58.4 years, median parity was two, and
      95.4% were Caucasian. The pattern of referral was as follows: 10% continued care
      at the tertiary center where mesh or graft was initially inserted, 18% were
      referred by the surgeon who initially implanted the mesh or graft, 71% were
      referred from an outside secondary health care provider, and 1% was self
      referred. CONCLUSION: The majority of patients presenting to our clinic with mesh
      vaginal mesh complications were referred by someone other than the implanting
      surgeon.

PMID- 23155844
TI  - Interfaces between electronic medical record (EMR/EHR) technology and people in
      American medicine: insight, imagination, and relationships in clinical practice.

PMID- 23155845
TI  - Looking forward: Where does the emerging field of genomics fit in the health care
      delivery system?

PMID- 23155846
TI  - Five things physicians and patients should question.

PMID- 23155847
TI  - Specialty care.

PMID- 23155848
TI  - The Warren Alpert Medical School of Brown University class of 2012.

PMID- 23155849
TI  - Warren Alpert Medical School's Doctoring program: a comprehensive, integrated
      clinical curriculum.

PMID- 23155850
TI  - Curriculum innovation at the Warren Alpert Medical School of Brown University.

PMID- 23155851
TI  - Assessing clinical competence of graduating medical students at the Warren Alpert
      Medical School of Brown University.

PMID- 23155852
TI  - Neighborhood health differentials in Warwick, RI: an analysis of risk factors.

PMID- 23155853
TI  - Subungual glomus tumor.

PMID- 23155854
TI  - AED's in the dental office.

PMID- 23155855
TI  - You have to be the difference.

PMID- 23155856
TI  - Health care reform update.

PMID- 23155857
TI  - Got yield? 4 asset classes for creating investment income: part 2.

PMID- 23155858
TI  - Exposure to airborne ultrafine particles from cooking in Portuguese homes.
AB  - Cooking was found to be a main source of submicrometer and ultrafine aerosols
      from gas combustion in stoves. Therefore, this study consisted of the
      determination of the alveolar deposited surface area due to aerosols resulting
      from common domestic cooking activities (boiling fish, vegetables, or pasta, and
      frying hamburgers and eggs). The concentration of ultrafine particles during the
      cooking events significantly increased from a baseline of 42.7 microm2/cm3
      (increased to 72.9 microm2/cm3 due to gas burning) to a maximum of 890.3
      microm2/cm3 measured during fish boiling in water and a maximum of 4500
      microm2/cm3 during meat frying. This clearly shows that a domestic activity such
      as cooking can lead to exposures as high as those of occupational exposure
      activities. IMPLICATIONS: The approach of this study considers the determination
      of alveolar deposited surface area of aerosols generated from cooking activities,
      namely, typical Portuguese dishes. This type of measurement has not been done so
      far, in spite of the recognition that cooking activity is a main source of
      submicrometer and ultrafine aerosols. The results have shown that the levels of
      generated aerosols surpass the outdoor concentrations in a major European town,
      which calls for further determinations, contributing to a better assessment of
      exposure of individuals to domestic activities such as this one.

PMID- 23155859
TI  - Multispecies remote sensing measurements of vehicle emissions on Sherman Way in
      Van Nuys, California.
AB  - As part of the 2010 Van Nuys tunnel study, researchers from the University of
      Denver measured on-road fuel-specific light-duty vehicle emissions from nearly
      13,000 vehicles on Sherman Way (0.4 miles west of the tunnel) in Van Nuys,
      California, with its multispecies Fuel Efficiency Automobile Test (FEAT) remote
      sensor a week ahead of the tunnel measurements. The remote sensing mean gram per
      kilogram carbon monoxide (CO), hydrocarbon (HC), and oxide of nitrogen (NO(x))
      measurements are 8.9% lower 41% higher, and 24% higher than the tunnel
      measurements, respectively. The remote sensing CGO/NO(x) and HC/NO(x) mass ratios
      are 28% lower and 20% higher than the comparable tunnel ratios. Comparisons with
      the historical tunnel measurements show large reductions in CO, HC, and NO(x)
      over the past 23 yr, but little change in the HC/NO(x) mass ratio since 1995. The
      fleet CO and HC emissions are increasingly dominated by a few gross emitters,
      with more than a third of the total emissions being contributed by less than 1%
      of the fleet. An example of this is a 1995 vehicle measured three times with an
      average HC emission of 419 g/kg fuel (two-stroke snowmobiles average 475 g/kg
      fuel), responsible for 4% of the total HC emissions. The 2008 economic downturn
      dramatically reduced the number of new vehicles entering the fleet, leading to an
      age increase (> 1 model year) of the Sherman Way fleet that has increased the
      fleet's ammonia (NH3) emissions. The mean NH3 levels appear little changed from
      previous measurements collected in the Van Nuys tunnel in 1993. Comparisons
      between weekday and weekend data show few fleet differences, although the
      fraction of light-duty diesel vehicles decreased from the weekday (1.7%) to
      Saturday (1.2%) and Sunday (0.6%). IMPLICATIONS: On-road remote sensing emission
      measurements of light-duty vehicles on Sherman Way in Van Nuys, California, show
      large historical emission reductions for CO and HC emissions despite an older
      fleet arising from the 2008 economic downturn. Fleet CO and HC emissions are
      increasingly dominated by a few gross emitters, with a single 1995 vehicle
      measured being responsible for 4% of the entire fleet's HC emissions. Finding and
      repairing and/or scrapping as little as 2% of the fleet would reduce on-road
      tailpipe emissions by as much as 50%. Ammonia emissions have locally increased
      with the increasing fleet age.

PMID- 23155860
TI  - Comparison of the MOVES2010a, MOBILE6.2, and EMFAC2007 mobile source emission
      models with on-road traffic tunnel and remote sensing measurements.
AB  - The Desert Research Institute conducted an on-road mobile source emission study
      at a traffic tunnel in Van Nuys, California, in August 2010 to measure fleet
      averaged, fuel-based emission factors. The study also included remote sensing
      device (RSD) measurements by the University of Denver of 13,000 vehicles near the
      tunnel. The tunnel and RSD fleet-averaged emission factors were compared in blind
      fashion with the corresponding modeled factors calculated by ENVIRON
      International Corporation using U.S. Environmental Protection Agency's (EPA's)
      MOVES2010a (Motor Vehicle Emissions Simulator) and MOBILE6.2 mobile source
      emission models, and California Air Resources Board's (CARB's) EMFAC2007
      (EMission FACtors) emission model. With some exceptions, the fleet-averaged
      tunnel, RSD, and modeled carbon monoxide (CO) and oxide of nitrogen (NO(x))
      emission factors were in reasonable agreement (+/- 25%). The nonmethane
      hydrocarbon (NMHC) emission factors (specifically the running evaporative
      emissions) predicted by MOVES were insensitive to ambient temperature as compared
      with the tunnel measurements and the MOBILE- and EMFAC-predicted emission
      factors, resulting in underestimation of the measured NMHC/NO(x) ratios at higher
      ambient temperatures. Although predicted NMHC/NO(x) ratios are in good agreement
      with the measured ratios during cooler sampling periods, the measured NMHC/NO(x)
      ratios are 3.1, 1.7, and 1.4 times higher than those predicted by the MOVES,
      MOBILE, and EMFAC models, respectively, during high-temperature periods. Although
      the MOVES NO(x) emission factors were generally higher than the measured factors,
      most differences were not significant considering the variations in the modeled
      factors using alternative vehicle operating cycles to represent the driving
      conditions in the tunnel. The three models predicted large differences in NO(x)
      and particle emissions and in the relative contributions of diesel and gasoline
      vehicles to total NO(x) and particulate carbon (TC) emissions in the tunnel.
      IMPLICATIONS: Although advances have been made to mobile source emission models
      over the past two decades, the evidence that mobile source emissions of carbon
      monoxide and hydrocarbons in urban areas were underestimated by as much as a
      factor of 2-3 in past inventories underscores the need for on-going verification
      of emission inventories. Results suggest that there is an overall increase in
      motor vehicle NMHC emissions on hot days that is not fully accounted for by the
      emission models. Hot temperatures and concomitant higher ratios of NMHC emissions
      relative to NO(x) both contribute to more rapid and efficient formation of ozone.
      Also, the ability of EPA's MOVES model to simulate varying vehicle operating
      modes places increased importance on the choice of operatingmodes to evaluate
      project-level emissions.

PMID- 23155861
TI  - Modeling an air pollution episode in northwestern United States: identifying the
      effect of nitrogen oxide and volatile organic compound emission changes on air
      pollutants formation using direct sensitivity analysis.
AB  - Air quality impacts of volatile organic compound (VOC) and nitrogen oxide (NO(x))
      emissions from major sources over the northwestern United States are simulated.
      The comprehensive nested modeling system comprises three models: Community
      Multiscale Air Quality (CMAQ), Weather Research and Forecasting (WRF), and Sparse
      Matrix Operator Kernel Emissions (SMOKE). In addition, the decoupled direct
      method in three dimensions (DDM-3D) is used to determine the sensitivities of
      pollutant concentrations to changes in precursor emissions during a severe smog
      episode in July of 2006. The average simulated 8-hr daily maximum O3
      concentration is 48.9 ppb, with 1-hr O3 maxima up to 106 ppb (40 km southeast of
      Seattle). The average simulated PM2.5 (particulate matter with an aerodynamic
      diameter < 2.5 microm) concentration at the measurement sites is 9.06 microg m(
      3), which is in good agreement with the observed concentration (8.06 microg m(
      3)). In urban areas (i.e., Seattle, Vancouver, etc.), the model predicts that, on
      average, a reduction of NO(x) emissions is simulated to lead to an increase in
      average 8-hr daily maximum O3 concentrations, and will be most prominent in
      Seattle (where the greatest sensitivity is -O.2 ppb per % change of mobile
      sources). On the other hand, decreasing NO(x) emissions is simulated to decrease
      the 8-hr maximum O3 concentrations in remote and forested areas. Decreased NO(x)
      emissions are simulated to slightly increase PM2.5 in major urban areas. In urban
      areas, a decrease in VOC emissions will result in a decrease of 8-hr maximum O3
      concentrations. The impact of decreased VOC emissions from biogenic, mobile,
      nonroad, and area sources on average 8-hr daily maximum O3 concentrations is up
      to 0.05 ppb decrease per % of emission change, each. Decreased emissions of VOCs
      decrease average PM2.5 concentrations in the entire modeling domain. In major
      cities, PM2.5 concentrations are more sensitive to emissions of VOCs from
      biogenic sources than other sources of VOCs. These results can be used to
      interpret the effectiveness of VOC or NO(x) controls over pollutant
      concentrations, especially for localities that may exceed National Ambient Air
      Quality Standards (NAAQS). IMPLICATIONS: The effect of NO(x) and VOC controls on
      ozone and PM2.5 concentrations in the northwestern United States is examined
      using the decoupled direct method in three dimensions (DDM-3D) in a state-of-the
      art three-dimensional chemical transport model (CMAQ). NO(x) controls are
      predicted to increase PM2.5 and ozone in major urban areas and decrease ozone in
      more remote and forested areas. VOC reductions are helpful in reducing ozone and
      PM2.5 concentrations in urban areas. Biogenic VOC sources have the largest impact
      on O3 and PM2.5 concentrations.

PMID- 23155862
TI  - Optimization of a horizontal-flow biofilm reactor for the removal of methane at
      low temperatures.
AB  - Three pilot-scale, horizontal-flow biofilm reactors (HFBRs 1-3) were used to
      treat methane (CH4)-contaminated air to assess the potential of this technology
      to manage emissions from agricultural activities, waste and wastewater treatment
      facilities, and landfills. The study was conducted over two phases (Phase 1,
      lasting 90 days and Phase 2, lasting 45 days). The reactors were operated at 10
      degrees C (typical of ambient air and wastewater temperatures in northern
      Europe), and were simultaneously dosed with CH4-contaminated air and a synthetic
      wastewater (SWW). The influent loading rates to the reactors were 8.6 g CH4/m3/hr
      (4.3 g CH4/m2 TPSA/hr; where TPSA is top plan surface area). Despite the low
      operating temperatures, an overall average removal of 4.63 g CH4/m3/day was
      observed during Phase 2. The maximum removal efficiency (RE) for the trial was
      88%. Potential (maximum) rates of methane oxidation were measured and indicated
      that biofilm samples taken from various regions in the HFBRs had mostly equal CH4
      removal potential. In situ activity rates were dependent on which part of the
      reactor samples were obtained. The results indicate the potential of the HFBR, a
      simple and robust technology, to biologically treat CH4 emissions. IMPLICATIONS:
      The results of this study indicate that the HFBR technology could be effectively
      applied to the reduction of greenhouse gas emissions from wastewater treatment
      plants and agricultural facilities at lower temperatures common to northern
      Europe. This could reduce the carbon footprint of waste treatment and
      agricultural livestock facilities. Activity tests indicate that methanotrophic
      communities can be supported at these temperatures. Furthermore, these data can
      lead to improved reactor design and optimization by allowing conditions to be
      engineered to allow for improved removal rates, particularly at lower
      temperatures. The technology is simple to construct and operate, and with some
      optimization of the liquid phase to improve mass transfer, the HFBR represents a
      viable, cost-effective solution for these emissions.

PMID- 23155863
TI  - The addition of modified attapulgite reduces the emission of nitrous oxide and
      ammonia from aerobically composted chicken manure.
AB  - The acceleration of the composting process and the improvement of compost quality
      have been explored by evaluating the efficacy of various additives, inoculating
      with specific microorganisms and the application of various biosurfactants. The
      magnesium-aluminum silicate attapulgite is a low-cost potential composting
      additive, but its effects on aerobic composting are unknown. This study
      investigated the effects of attapulgite application on compost production and
      quality during the aerobic composting of chicken manure. Addition of attapulgite
      significantly increased the temperature (p < 0.05) while it reduced compost total
      organic carbon (TOC) and seed germination indices (GIs) throughout the process.
      Its addition enhanced nitrate concentrations, promoted organic matter
      degradation, increased seed germination indices, and accelerated the composting
      process. Interestingly, attapulgite addition did not increase the population of
      ammonia-oxidizing bacteria. These results suggest that attapulgite is a good
      additive for the composting industry. IMPLICATIONS: We investigated the addition
      of two forms of attapulgite during aerobic composting of chicken manure to
      determine their effects under strict composting environmental parameter control.
      Our results provides primary evidence that attapulgite may have potential for
      application in the composting industry. All treatments showed no increase within
      the first 15 days. However, emissions increased for all treatments within 15-45
      days, reaching approximately 6300, 2000, and 4000 mg/m2 from the control,
      artifactitious attapulgite, and raw attapulgite treatments, respectively.

PMID- 23155864
TI  - Air impacts from three alternatives for producing JP-8 jet fuel.
AB  - To increase U.S. petroleum energy independence, the University of Texas at
      Arlington (UT Arlington) has developed a direct coal liquefaction process which
      uses a hydrogenated solvent and a proprietary catalyst to convert lignite coal to
      crude oil. This sweet crude can be refined to form JP-8 military jet fuel, as
      well as other end products like gasoline and diesel. This paper presents an
      analysis of air pollutants resulting from using UT Arlington's liquefaction
      process to produce crude and then JP-8, compared with 2 alternative processes:
      conventional crude extraction and refining (CCER), and the Fischer-Tropsch
      process. For each of the 3 processes, air pollutant emissions through production
      of JP-8 fuel were considered, including emissions from upstream extraction/
      production, transportation, and conversion/refining. Air pollutants from the
      direct liquefaction process were measured using a LandTEC GEM2000 Plus, Draeger
      color detector tubes, OhioLumex RA-915 Light Hg Analyzer, and SRI 8610 gas
      chromatograph with thermal conductivity detector. According to the screening
      analysis presented here, producing jet fuel from UT Arlington crude results in
      lower levels of pollutants compared to international conventional crude
      extraction/refining. Compared to US domestic CCER, the UTA process emits lower
      levels of CO2-e, NO(x), and Hg, and higher levels of CO and SO2. Emissions from
      the UT Arlington process for producing JP-8 are estimated to be lower than for
      the Fischer-Tropsch process for all pollutants, with the exception of CO2-e,
      which were high for the UT Arlington process due to nitrous oxide emissions from
      crude refining. When comparing emissions from conventional lignite combustion to
      produce electricity, versus UT Arlington coal liquefaction to make JP-8 and
      subsequent JP-8 transport, emissions from the UT Arlington process are estimated
      to be lower for all air pollutants, per MJ of power delivered to the end user.
      IMPLICATIONS: The United States currently imports two-thirds of its crude oil,
      leaving its transportation system especially vulnerable to disruptions in
      international crude supplies. At current use rates, U.S. coal reserves (262
      billion short tons, including 23 billion short tons lignite) would last 236
      years. Accordingly, the University of Texas at Arlington (UT Arlington) has
      developed a process that converts lignite to crude oil, at about half the cost of
      regular crude. According to the screening analysis presented here, producing jet
      fuel from UT Arlington crude generates lower levels of pollutants compared to
      international conventional crude extraction/refining (CCER).

PMID- 23155865
TI  - Effects of activated carbon surface properties on the adsorption of volatile
      organic compounds.
AB  - Physical and chemical properties of activated carbon (AC) were analyzed to
      investigate the effects of adsorbate properties on AC adsorption performance.
      Fixed-bed adsorption experiments were conducted with toluene, acetone, and xylene
      as adsorbates. From the results, the adsorption capacities of the three
      adsorbates had the following order: xylene > toluene > acetone. The correlation
      between experimental data and adsorbate properties was also analyzed. The results
      showed that different functional groups corresponding to the properties of
      adsorbates influenced the adsorptive properties of AC differently. The adsorption
      capacity of AC increased linearly as the molecular weight, dynamic diameter,
      boiling point, and density of the adsorbate increased. However, adsorption
      capacity decreased as the polarity index and vapor pressure of the adsorbate
      increased. For adsorption onto three types of AC, the adsorption energies of the
      three adsorbates had the following order: xylene > toluene > acetone.
      IMPLICATIONS: This paper focused on the research on adsorption behavior of
      activated carbon based on adsorbate properties. Adsorption experiments were
      conducted under the same condition while the adsorbates were toluene, acetone,
      and xylene, respectively. Correlation analysis between experimental data and
      adsorbate properties was conducted. The different groups have different influence
      on the adsorptive properties of ACs. The adsorption capacity of activated carbon
      increases with the increase of adsorbate molecular weight, dynamic diameter,
      boiling point, and density, and that this relationship is linear. The
      relationship between adsorption capacity and the polarity index and vapor
      pressure of adsorbate shows an opposite trend, and the adsorption capacities and
      adsorption energies of three kinds of activated carbon for these three adsorbates
      had the following order: xylene > toluene > acetone.

PMID- 23155866
TI  - Comparison of the purification performance and microbial community functional
      diversity in flow-directional-switching and unidirectional-flow biotrickling
      filters.
AB  - Because of the characteristics of low operating cost and convenient operation,
      the biotrickling filter is extensively researched and used to treat low
      concentration waste gas contaminated by volatile organic compounds (VOCs) and
      other odors. In this paper, two laboratory-scale biotrickling filters were
      constructed and toluene was selected as the sole carbon source, and the effects
      of different waste-gas flow configuration patterns on the purification capacity
      and the microbial community functional diversity of biotrickling filters were
      evaluated. The results indicated that the flow-directional-switching (FDS)
      biotrickling filter had better purification performance, and the maximum
      elimination capacity reached 480 g x m(-3) x hr(-1), which was 17.1% higher than
      conventional unidirectional-flow (UF) biotrickling filter. Comparing the
      purification capacities of different sections in two biotrickling filters, the
      maximum toluene elimination capacity of section III in FDS system could reach 542
      g x m(-3) x hr(-1), which was 2.8 times as great as that in UF system, which
      resulted from the difference of elimination capacity in two systems. By analyzing
      the metabolic activity of two systems by community-level physiological profiling
      (CLPP) with Biolog (Biolog Inc., Hayward, CA) ECO-plate technique, metabolic
      activity in three sections of FDS system was higher than that of UF system. The
      metabolic activity was the highest in section III of FDS system and 46.8% higher
      than that of UF system. Shannon index and McIntosh index of section III in FDS
      system were 6.2% and 31.5% higher, respectively, than those of UF system.
      IMPLICATIONS: The flow-directional-switching (FDS) biotrickling filter had a
      better purification performance than unidirectional-flow (UF) biotrickling filter
      at high inlet loadings, because FDS produced a more uniform distribution of
      biomass and microbial metabolic capacity along the length of the packed bed
      without diminishing activity and removal capacity in the inlet section.

PMID- 23155867
TI  - Gas-phase elemental mercury removal in a simulated combustion flue gas using TiO2
      with fluorescent light.
AB  - A previously proposed technology incorporating TiO2 into common household
      fluorescent lighting was further tested for its Hg0 removal capability in a
      simulated flue-gas system. The flue gas is simulated by the addition of O2, SO2,
      HCl, NO, H2O, and Hg0, which are frequently found in combustion facilities such
      as waste incinerators and coal-fired power plants. In the O2 + N2 + Hg0
      environment, a Hg0 removal efficiency (etaHg) greater than 95% was achieved.
      Despite the tendency for etaHg to decrease with increasing SO2 and HCl, no
      significant drop was observed at the tested level (SO2: 5-300 ppm, HCl: 30-120
      ppm(v)). In terms of NO and moisture, a significant negative effect on etaHg was
      observed for both factors. NO eliminated the OH radical on the TiO2 surface,
      whereas water vapor caused either the occupation of active sites available to Hg0
      or the reduction of Hg0 by free electron. However, the negative effect of NO was
      minimized (etaHg > 90%) by increasing the residence time in the photochemical
      reactor. The moisture effect can be avoided by installing a water trap before the
      flue gas enters the Hg0 removal system. IMPLICATIONS: This paper reports a novel
      technology for a removal of gas-phase elemental mercury (Hg0) from a simulated
      flue gas using TiO2-coated glass beads under a low-cost, easily maintainable
      household fluorescent light instead of ultraviolet (UV) light. In this study, the
      effects of individual chemical species (O2, SO2, HCl, NO, and water vapor) on the
      performance of the proposed technology for Hg0 removal are investigated. The
      result suggests that the proposed technology can be highly effective, even in
      real combustion environments such as waste incinerators and coal-fired power
      plants.

PMID- 23155868
TI  - Winter and summer PM2.5 chemical compositions in fourteen Chinese cities.
AB  - PM2.5 in 14 of China's large cities achieves high concentrations in both winter
      and summer with averages > 100 microg m(-3) being common occurrences. A grand
      average of 15 microg m(-3) was found for all cities, with a minimum of 27 microg
      m(-3) measured at Qingdao during summer and a maximum of 356 microg m(-3) at Xi
      'an during winter. Both primary and secondary PM2.5 are important contributors at
      all of the cities and during both winter and summer. While ammonium sulfate is a
      large contributor during both seasons, ammonium nitrate contributions are much
      larger during winter. Lead levels are still high in several cities, reaching an
      average of 1.68 microg m(-3) in Xi 'an. High correlations of lead with arsenic
      and sulfate concentrations indicate that much of it derives from coal combustion,
      rather than leaded fuels, which were phased out by calendar year 2000. Although
      limited fugitive dust markers were available, scaling of iron by its ratios in
      source profiles shows -20% of PM2.5 deriving from fugitive dust in most of the
      cities. Multipollutant control strategies will be needed that address incomplete
      combustion of coal and biomass, engine exhaust, and fugitive dust, as well as
      sulfur dioxide, oxides of nitrogen, and ammonia gaseous precursors for ammonium
      sulfate and ammonium nitrate. IMPLICATIONS: PM2.5 mass and chemical composition
      show large contributions from carbon, sulfate, nitrate, ammonium, and fugitive
      dust during winter and summer and across fourteen large cities. Multipollutant
      control strategies will be needed that address both primary PM2.5 emissions and
      gaseous precursors to attain China's recently adopted PM2.5 national air quality
      standards.

PMID- 23155870
TI  - Regulation. Francis for CQC.

PMID- 23155871
TI  - Care Quality Commission. New chief warns cuts threaten quality. Interview by
      Sarah Calkin.

PMID- 23155869
TI  - Adsorption behavior of toluene on modified 1X molecular sieves.
AB  - In this paper, the toluene adsorption/desorption properties of modified 13X
      molecular sieves (M-13X) are discussed. M-13X molecular sieves were prepared by
      acidic and steam treatments of 13X molecular sieves. The structural parameters of
      M-13X were evaluated and compared with those of other molecular sieves (HY, HZSM
      5, Cs7NaMOR, and a commercial 13X). The results show that the specific surface
      area, average pore diameter and pore volume of M-13X were 414.17 m2/g, 2.98 nm,
      and 0.31 mL/g, respectively. The pore size distribution of M-13X was 1.8-3.0 nm.
      Because of its larger Si/Al ratio (Si/Al = 6.77), the hydrophobicity of M-13X is
      much higher than that of 13X (Si/Al = 1.28), indicating that it is particularly
      well suited to toluene control applications. The saturation adsorption capacity
      of M-13X was 0.045 g/g for simulated toluene at a temperature of 293 K and a
      relative humidity of 50%. The optimal regeneration temperature of M-13X was 473 K
      for 120 min with a hot air flow rate of 140 L/min. IMPLICATIONS: The modified 13X
      molecular sieves (M-13X) are adsorbents with a high adsorption capacity and great
      hydrophobicity, suitable for the treatment of VOCs. The purpose of the present
      investigation is to provide a practical guide for their design.

PMID- 23155872
TI  - Talking dirty on healthcare waste. Interview by Claire Read.

PMID- 23155873
TI  - Justifying health priorities will not be easy.

PMID- 23155874
TI  - Doctors' orders.

PMID- 23155875
TI  - Performance management. 'Light the fire of enthusiasm'.

PMID- 23155876
TI  - Service improvement. Standard bearers.

PMID- 23155877
TI  - Foundation trusts. Why governors are the power behind the chairs.

PMID- 23155878
TI  - Quality. When patients become leaders.

PMID- 23155879
TI  - Survey. Dispensing wisdom.

PMID- 23155880
TI  - Legal. What happens after we pull the plug on PCTs?

PMID- 23155881
TI  - Public health. Serve up a change that lasts for life.

PMID- 23155882
TI  - Health reform: changing the therapeutic order of the nation (one step at a time).

PMID- 23155883
TI  - Building on conscious change: AHNA prepares for the role of advocacy.

PMID- 23155884
TI  - Holistic nursing and healthcare reform: challenges and opportunities.

PMID- 23155885
TI  - Health care reform begins with caring for ourselves.

PMID- 23155886
TI  - Patient-Centered Outcomes Research Institute: a response to public outcry for
      better use of healthcare dollars.

PMID- 23155887
TI  - Art of aromatherapy for end-of-life care.

PMID- 23155888
TI  - The happy dental patient.

PMID- 23155890
TI  - The human side of dentistry: all in the family.

PMID- 23155889
TI  - The battle of the bonds.

PMID- 23155891
TI  - Perserverance.

PMID- 23155892
TI  - Recruitment and retention of Alaska natives into nursing: elements enabling
      educational success.
AB  - In response to the underrepresentation of Alaska Native/American Indian nurses,
      nursing programs have implemented recruitment and retention efforts to support
      undergraduate Alaska Native/American Indian nursing students. The objective of
      this project was to provide graduates from the Recruitment and Retention of
      Alaska Natives into Nursing (RRANN) program the opportunity to identify program
      elements important to achieving academic success, levels of satisfaction, and
      make recommendations for future program direction. Findings suggest RRANN
      graduates viewed the program as vital to academic success. Recommendations
      include utilizing former graduates in recruitment and retention efforts, as
      mentors, and extending the program to benefit graduate students.

PMID- 23155893
TI  - Improving communication through accent modification: growing the nursing
      workforce.
AB  - A pilot program was developed to reduce the attrition rate among nursing
      students, especially those in ethnic and minority groups. The presence of accents
      and dialects among some of these students created communication difficulties
      which had the potential to negatively impact both academic success and patient
      safety in healthcare settings. Screening processes used to identify students with
      reduced speech intelligibility, specific accent modification methods and other
      speech improvement lessons implemented to improve overall communication abilities
      are described. Clarity of communication improved in all pilot program students.

PMID- 23155894
TI  - Faculty and student perceptions of academic incivility in the People's Republic
      of China.
AB  - This is the second article of a two-part series regarding nursing faculty and
      student perceptions of incivility in nursing education in the People's Republic
      of China (PRC). Nursing faculty from the United States of America (USA) and the
      PRC collaborated to conduct this empirical study. A sample of 382 Chinese nursing
      faculty and students responded to 4 open-ended questions on the Incivility in
      Nursing Education (INE) Survey. Both groups reported similar perceptions of
      uncivil behaviors, contributors to incivility, and ways to address the problem. A
      conceptual model for fostering civility in nursing education was adapted to
      illustrate the findings.

PMID- 23155895
TI  - Bias in the nursing workplace: implications for Latino(a) nurses.
AB  - The nursing shortage coupled with health inequities makes it imperative to retain
      nurses from diverse backgrounds in the workplace. Since Latinos are the fastest
      growing racial/ethnic group in the U.S., the issue is of particular importance.
      Thus, the purpose of this study was to measure the prevalence of bias in the
      nursing workplace as experienced by Latino(a) nurses. This descriptive study of
      Latino(a) nurses measured the prevalence of bias, its relationship to nurse
      retention in the nursing workplace, and additional factors in the workplace that
      were associated with bias. Results included that Latino(a) nurses both
      experienced and witnessed bias on a regular basis, along with negative comments
      by peers about their ethnicity. Significant correlations were found between
      experiences of bias and the study variables of witnessing bias, perceived levels
      of support, and time planning to remain in the workplace. As the nursing shortage
      continues and increases in severity, retaining nurses becomes as important as
      creating new nurses. Nurse managers, hospital administrators, and nurse educators
      must develop strategies to educate staff and promote non-biased interactions
      between nurses in the workplace, as well as to support nurses from diverse
      backgrounds.

PMID- 23155896
TI  - Overview of teaching strategies for cultural competence in nursing students.
AB  - Multiple curricular approaches are being used to teach cultural competency to
      nursing students in the United States in accordance with accrediting board
      standards. As nurse educators are searching for evidence based teaching
      practices, this article reviews the most commonly current teaching methods being
      used. Although a variety of methods are being implemented, little empirical
      evidence exists to suggest any one methodology for teaching cultural competency
      for nursing students produces significantly better outcomes. The use of clinical
      experiences, standardized patients and immersion experiences have produced the
      most favorable results which increase student awareness, knowledge and confidence
      in working with ethnically diverse patients.

PMID- 23155897
TI  - "Don't allow nursing to surrender its voice".

PMID- 23155898
TI  - Trusts hire staff to ensure safety.

PMID- 23155899
TI  - "We will be watching the progress on maternity pledges".

PMID- 23155900
TI  - "The stage 1 mentor role for new nurses needs questioning".

PMID- 23155901
TI  - What are the barriers to good mentoring?
AB  - This article reports on a study exploring the barriers to successful mentoring of
      pre-registration nursing and midwifery students in practice, and the support
      required by mentors. When asked what barriers could affect the quality of
      mentoring provided, 70% of the 199 mentors taking part in the study cited lack of
      time and 67% cited conflict between the competing demands of being a mentor and
      providing patient care. Some 41% of the mentors received very little protected
      time from clinical duties to support and assess students. Mentors said they
      needed more protected time, help with practice assessment documentation and
      regular mentor updates.

PMID- 23155902
TI  - Advances in patients' cancer journey.

PMID- 23155903
TI  - An inclusive approach to personality disorders.
AB  - Personality disorder is one of the most misunderstood of mental health disorders.
      Historically, people with this diagnosis have experienced exclusion and rejection
      from mainstream mental health services and wider multi-agency services. This
      article describes the development of a new strategy to build strong, seamless
      links across multi-agency services with the aim of providing timely
      interventions, improving patient experience and reducing the likelihood of
      transitions to more costly services.

PMID- 23155904
TI  - Managing acute painful sickle cell episodes in hospital.

PMID- 23155905
TI  - A reappraisal of herbal medicinal products.
AB  - Complementary and alternative medicine is increasingly popular, and encompasses a
      number of systems and therapies based on diverse theories and practices, such as
      homoeopathy, traditional herbalism, reiki, ayurvedic medicine and traditional
      Chinese medicine. While many are based on metaphysical concepts for which there
      is no sound evidence, for herbal medicines there is a rational, scientific basis
      and increasing clinical evidence. This article suggests herbal medicines should
      no longer be considered part of CAM, but instead sit alongside conventional
      medicines.

PMID- 23155906
TI  - Dedicated to nursing.

PMID- 23155907
TI  - Driven by seeking out the details.

PMID- 23155908
TI  - Pertussis has re-emerged.

PMID- 23155909
TI  - Medical humanities--serious academic pursuit or doorway to dilettantism?

PMID- 23155910
TI  - Reporting biochemical toxicology to the coroner must be improved.

PMID- 23155911
TI  - Concealed pregnancy: prevalence, perinatal measures and socio-demographics.
AB  - A target group of women who concealed their pregnancy (n = 43) was compared to an
      aged-matched control group (n = 30) that experienced a crisis pregnancy.
      Comparisons were also made with a larger dataset (n = 6363) of births in
      University Hospital Galway (UHG) (normative group). Data was analysed using the
      Chi-square test and the Kolmogorov-Smirnoff two-sample test. The number of women
      from the target group that were from a rural background was 28 (65%), compared to
      10 (33%) from the control group. The number of women from the target group that
      feared a negative parental reaction to the pregnancy was 34 (79%), compared to 12
      (40%) from the control group. The birth weight in the target group was 4009 lower
      than the normative birth weight. The average age of women who concealed was 8
      years lower than the normative age. The prevalence of concealed pregnancy in UHG
      was one in every 148 births.

PMID- 23155913
TI  - Successful introduction of ring-fenced inpatient surgical beds in a general
      hospital setting.
AB  - This study aimed to assess the impact of ring-fenced inpatient general surgical
      beds on day of surgery (DOS) admission, duration of elective inpatient stay
      (DEIS), and cancellation rates over a 6 month period. In June 2010 17 of 60
      surgical inpatient beds were decommissioned. The remainder (43) were ring-fenced
      for general surgery patients only. Comparative analysis examining admission
      rates, cancellation rates, and theatre activity was performed between a reference
      period (January-June 2010) and the study period (July-December 2010). Complexity
      of all operations was graded according to an index schedule of procedures. There
      was no difference between the reference and study periods in volumes of elective
      admissions (472 [53.03%] vs. 418 [4797%]) and emergency admissions (928 [50.03%]
      vs. 927 [49.97%]). DOS admissions increased 5-fold during the study period (38
      [8.1%] vs. 190 [45.5%], P < 0.001). Average duration of elective inpatient stay
      reduced from 4.3 days to 3.06 days in the study period (P < 0.001). No difference
      was observed in volume of operations performed at all levels of complexity. There
      were 78 (58.2%) cancellations during the reference period and 56 (41.8%) during
      the study period with patient non-attendance the most common cause for
      cancellation in both periods. Ring-fenced surgical beds facilitated higher DOS
      admission rates and shorter duration of elective inpatient stay, leading to more
      efficient use of hospital resources.

PMID- 23155912
TI  - Weaning onto solid foods: some of the challenges.
AB  - Weaning--the transition from milk to solid food--influences life-long health.
      Dietary challenges during weaning include providing sufficient critical nutrients
      such as iron with minimal added sugar and fat and no added salt. This study
      assessed the inclusion of iron-containing red meat in infant diets before age one
      year, and the Irish commercial baby food environment. Of mothers with an infant
      under 30 months of age who were surveyed in shopping centres in Ireland (n195),
      82% (n159) reported wanting more weaning information. A quarter (n24) of infants
      over age 12 months (n97) received no iron-containing red meat before age one
      year. A scan of commercial baby foods in Ireland identified 448 products. While
      all complied with baby food legislation, 15% (n69) were intrinsically high in
      sugar and fat, or contained added salt. This study indicates the need for
      specific guidance on best infant feeding practice in Ireland.

PMID- 23155914
TI  - Geriatric medicine in the emergency department.
AB  - Studies suggest older adults attending emergency departments(ED) benefit from
      specialist geriatric medicine evaluation. Findings from a pilot ED Geriatric
      Medicine(GM) liaison service in our 480-bed university hospital are presented.
      This is not a randomized controlled trial. Service comprised consultant
      geriatrician and senior trainee-led sessions during daytime working hours. Senior
      ED personnel selected appropriate patients. GM service also took over ED medical
      admissions aged 80, 1 in 9 days from General Internal Medicine(GIM). 49% of 284
      patients (83.5 +/- 6.8 years) referred, were discharged from ED with appropriate
      follow-up. Inpatient analysis comprised 51% admitted to GIM, GM and specialist
      services as per on-call rota and 268 patients taken over from GIM. Patients under
      GM had shorter length of stay (p < 0.001). The findings suggest specialty
      specific geriatric medicine management of the older adult presenting to ED can
      improve service and patient outcomes.

PMID- 23155915
TI  - A pain in the neck--medical student attitudes to the Orthopaedic spine.
AB  - Considerable deficiencies exist in the teaching of Orthopaedic medicine. This
      study aimed (i) to determine if spinal surgery was the Orthopaedic specialty that
      students found most difficult, (ii) to appraise attitudes towards teaching of the
      spine, and (iii) to suggest ways teaching might be improved. A questionnaire on
      Orthopaedic teaching was given to 238 final year medical students in Ireland.
      Perceived difficulties with spinal surgery were compared to seven other
      Orthopaedic sub-specialties. Suggestions made on how to maximise teaching
      potential included 69 (29%) for more tutorials, 43 (18%) for more lectures, 26
      (11%) suggested a more structured training programme and 17 (7%) for increased
      use of online resources. The spine is one of the least popular Orthopaedic
      subspecialties and considerable deficiencies exist in its education.

PMID- 23155916
TI  - Pulmonary Mycobacterium szulgai infection.
AB  - There has been an increase in the number of pulmonary infections caused by non
      tuberculous mycobacteria (NTM) in the non HIV-infected population with a
      heightened awareness clinically and in the laboratory of the significance of
      these respiratory isolates and newer identification techniques. As far as we are
      aware, this is the first case report of pulmonary Mycobacteium szulgai infection
      in Ireland.

PMID- 23155917
TI  - Laparoscopic Nissen fundoplication post-oesophageal stenting: an unusual case.
AB  - Laparoscopic Nissen fundoplication post-oesophageal stenting is uncommon and yet
      to be reported. We report the case of a 57-year-old palliative lady who underwent
      surgery for symptomatic relief of severe gastrooesophageal reflux post
      oesophageal stenting. Surgery was carried out successfully with no complications.
      On the evening post-surgery she was able to lie supine for the first time in
      months without symptoms of reflux. In conclusion, surgery is still valuable and
      may play an important role, even in a palliative setting.

PMID- 23155918
TI  - Deep brain stimulation in ireland for Parkinson's disease and essential tremor.
AB  - Deep brain stimulation (DBS) is highly effective neurosurgery for idiopathic
      Parkinson's disease (IPD), essential tremor (ET) and primary dystonia. DBS
      involves stereotactic surgical implantation of a battery-operated stimulator into
      deep brain nuclei. Irish patients are referred abroad for DBS and have to travel
      repeatedly for pre and post-operative care resulting in stress, anxiety and
      hardship. Safe pre and post-operative care of these complex, ageing patients is
      compromised by the absence of a DBS service in Ireland. Moreover, both DBS
      surgery and the subsequent post-operative care abroad incurs substantial cost to
      the state. The Dublin Neurological Institute at the Mater Misericordiae
      University Hospital (DNI) is a non-profit institute for the care of patients with
      neurological diseases. The DNI developed, in collaboration with the Mater Private
      Hospital (MPH) and the Walton Centre, Liverpool, a DBS programme in 2008/2009. We
      performed DBS at the Mater Campus on three carefully selected patients from a
      cohort of movement disorder patients attending the DNI and continue to provide
      pre-operative assessment and post operative care for patients following DBS in
      Ireland and abroad.

PMID- 23155919
TI  - Improving immunisation uptake across Europe.

PMID- 23155920
TI  - Informed consent in refractive eye surgery: learning from patients and the
      courts.
AB  - Refractive eye laser surgery involves ablation of the cornea using excimer laser
      to correct short or long sightedness and thus negate the need for glasses and/or
      contact lenses. With the doctrine of informed consent often central to claims of
      medical negligence in this area, we examine the attitudes, understanding and
      recall of patients to consent for refractive surgery and outline the relevant
      law. 102 patients undergoing first time refractive surgery were analysed to
      examine their understanding and recall of the consenting process. Only 2 patients
      remembered all 5 risks outlined preoperatively, while 11 remembered no risks at
      all. 65% of patients consulted the internet to learn more about the operation.
      Our study demonstrates that patient understanding and recall remains poor. A
      signed consent form is not, of itself a full defence to allegations of uninformed
      consent, and the consent process must be comprehensive.

PMID- 23155921
TI  - Neonatal meningitis: a diagnostic dilemma.

PMID- 23155922
TI  - VACTERL association or VATER syndrome.

PMID- 23155923
TI  - Risk of rehospitalisation from an 'off-site' rehabilitation unit for older
      adults.

PMID- 23155924
TI  - The effect of public deposit of scientific articles on readership.
AB  - A longitudinal cohort analysis of 3,499 articles published in 12 physiology
      journals reveals a 14% reduction in full text article downloads when they are
      made publicly available from the PubMed Central archive. The loss of article
      readership from the journal website may weaken the ability of the publisher to
      build communities of interest around the research article, impede the
      communication of news and events with society members and reduce the perceived
      value of the journal to institutional subscribers.

PMID- 23155925
TI  - The significance of the Porter Development Fellowship for my career.

PMID- 23155926
TI  - The graduate student portfolio: organize and energize your career development.

PMID- 23155927
TI  - Common Fund programs: what are they and are you eligible for funding?

PMID- 23155928
TI  - Individual account retirement plans: an analysis of the 2010 survey of consumer
      finances.

PMID- 23155930
TI  - Cardiac surgery inquiry aftermath.

PMID- 23155929
TI  - Sources of health insurance and characteristics of the uninsured: analysis of the
      March 2012 Current Population Survey.
AB  - HEALTH COVERAGE RATE INCREASED, UNINSURED DOWN: The percentage of the nonelderly
      population (under age 65) with health insurance coverage increased to 82 percent
      in 2011, notable since increases in health insurance coverage have been recorded
      in only five years since 1994. EMPLOYMENT-BASED COVERAGE REMAINS DOMINANT SOURCE
      OF HEALTH COVERAGE, BUT CONTINUES TO ERODE: Employment-based health benefits
      remain the most common form of health coverage in the United States, though it
      represents a declining share. In 2011, 58.4 percent of the nonelderly population
      had employment-based health benefits, down from the peak of 69.3 percent in 2000,
      during the 1994-2011 period. PUBLIC PROGRAM COVERAGE IS EXPANDING: Public program
      health coverage expanded as a percentage of the population in 2011, accounting
      for 22.5 percent of the nonelderly population. Enrollment in Medicaid and the
      State Children's Health Insurance Program (S-CHIP) also increased to a combined
      46.9 million in 2011, covering 17.6 percent of the nonelderly population,
      significantly above the 10.2 percent level of 1999. INDIVIDUAL COVERAGE STABLE:
      The percentage represented by individually purchased health coverage was
      unchanged in 2011 and has basically hovered in the 6-7 percent range since 1994.
      WHAT TO EXPECT IN 2012: The unemployment rate in 2012 has been about 8 percent
      since the beginning of the year, and remains high amidst a still-sluggish
      economy. As a result, the nation is likely to see a corresponding erosion of
      employment-based health benefits when the data for 2012 are released next year.
      Until the economy gains enough strength to have a substantial impact on the labor
      market, a rebound in employment-based coverage is unlikely.

PMID- 23155931
TI  - Whooping cough case numbers rise across the UK and US.

PMID- 23155932
TI  - Annual flu vaccinations for children announced.

PMID- 23155933
TI  - Heart surgery reorganise into seven larger centres.

PMID- 23155934
TI  - The importance of correctly reading a child's distress.

PMID- 23155935
TI  - Value of interaction.

PMID- 23155936
TI  - Brain tumours and cancer: insights as a parent and a nurse.
AB  - Being told your child has cancer and that her short-term survival is tenuous
      probably rates among the most devastating news a parent can ever hear. This
      article examines one family's personal journey through the cancer treatment of
      their teenage daughter. The author, a registered nurse, also offers insights for
      nursing practice about how to deal with patients and their families.

PMID- 23155937
TI  - An audit of chemotherapy-induced nausea and vomiting in children.
AB  - An audit was conducted of the management of chemotherapy-induced nausea and
      vomiting in children and young people in the national Irish paediatric cancer
      unit. Over three months, the anti-emetic medication and the incidence of nausea
      and vomiting in 50 consecutive patient episodes were recorded among 25 children
      receiving chemotherapy for diverse malignancies. Anti-emetic prescription was
      found to be unrelated to the emetogenic potential of the chemotherapy received,
      so that effectiveness varied. Dexamethasone was used in only one case. Twenty
      children did not take any anti-emetics following discharge, although 11
      experienced delayed vomiting, evidence-based guidelines were established and now
      include anti-emetic prescription that is proportional to the emetogenic potential
      of the chemotherapeutic regimen. It is also recommended that staff, patients,
      families and carers should receive education about the need for prescription and
      use of anti-emetics after discharge.

PMID- 23155938
TI  - Early intervention and management of adrenal insufficiency in children.
AB  - The endocrine disorder adrenal insufficiency includes inadequate production of
      the steroid hormone cortisol. This results in poor physiological responses to
      illness, trauma or other stressors and risk of adrenal crisis. Management is
      based on administration of hydrocortisone. It is important to avoid under- or
      over-treatment and increase the dosage during times of physiological stress. To
      reduce morbidity, hospital admissions and mortality, the education and
      empowerment of parents and carers, and prompt intervention when necessary are
      essential. A steroid therapy card for adrenal insufficiency containing personal
      information on a patient's condition was developed for use by families and their
      specialist centres.

PMID- 23155939
TI  - Training high: a clinical skills initiative for families and staff.
AB  - During the past 50 years the care of children and young people who are unwell in
      the UK has shifted out of the hospital environment and into the community and has
      become more complex, requiring the development among families and care staff of
      corresponding clinical skills. The ongoing initiative Training High aims to meet
      this need by offering appropriate training programmes to families and
      professional carers so they can safely undertake certain procedures. This article
      describes the success of one training project in England.

PMID- 23155940
TI  - Involving school students in selecting candidates for children's nursing.
AB  - This year-long project involved 26 academy school students aged 13-15 years
      taking an active role in selecting from candidates for children's nursing places
      at the University of the West of England. Meticulous planning, preparation,
      debriefing and awareness of safeguarding needs were all needed. Further aspects
      relating to increased pressures on academic time, recruitment and preparation of
      university student supporters, and project funding, also required attention. Some
      candidates reported the inclusion of school students to be challenging; others
      found it helpful in clarifying their career aspirations. The project has run for
      three years and further evaluations could measure the efficacy of this initiative
      to candidate selection. Other institutions may wish to consider adopting this or
      a similar approach.

PMID- 23155941
TI  - Take the pledge: Online personal health records help RNs, other consumers in
      their decision-making.

PMID- 23155943
TI  - Reduced Medicare spending could cost more than 750,000 jobs.

PMID- 23155942
TI  - Behind the technology: Nurses develop and use e-systems to make patient care,
      RNs' working life better.

PMID- 23155944
TI  - Health care as a basic human right.

PMID- 23155945
TI  - Technology helps to reduce nurses' risk to sharps injuries.

PMID- 23155946
TI  - Nurses leading in health care transformation. Interview by Susan Trossman.

PMID- 23155947
TI  - APRNs benefit from EHR incentive program.

PMID- 23155948
TI  - Cost growth 101 for the physician: what drives the rapidly growing health care
      costs?

PMID- 23155949
TI  - Women doctors' purses as an unrecognized fomite.
AB  - OBJECTIVE: Health care associated infections are serious problems for today's
      medical community. It is generally assumed that health care workers come in
      contact with pathologic bacteria and unwittingly transfer them to patients either
      directly with their hands, or indirectly through some inanimate object. If a
      doctor washes his or her hands before seeing a patient and then touches a
      colonized object, the benefit of hand washing may have been undone. Previous
      studies have identified stethoscopes, neck ties, mobile phones, keyboards, lab
      coats, and other commonly worn accessories as potential sources of disease
      transmission contributing to health care associated infections. Women doctors'
      purses have not previously been studied as a potential source of disease
      transmission. This study evaluated whether doctors' purses served as a potential
      source of disease transmission. METHODS: We performed a case-control study to
      determine if women doctors' purses were colonized more frequently than controls.
      Purses were obtained from women doctors who visit a hospital as part of their
      clinical responsibilities in the experimental group. Thirteen doctors fit the
      criteria of visiting an acute care facility while bringing a purse with them.
      Fourteen controls were non-health care women who had not visited a hospital in
      the past six months. RESULTS: We observed that nine of 13 doctors' purses were
      colonized with bacteria compared with two of 14 controls. CONCLUSIONS: This
      statistically significant finding demonstrates that there is a potential for a
      doctor's purse to serve as a vector for disease transmission. It is prudent for
      women health care workers to be aware that their purses may be a source of
      bacterial contamination. We, therefore, recommend that women practitioners use
      appropriate infection control measures whenever their purses are in the health
      care environment.

PMID- 23155950
TI  - How will the delivery of medical care be changing and does the lay public know
      enough about it?

PMID- 23155951
TI  - Response to Shifting standards of care.

PMID- 23155952
TI  - Response to Did I say that? Speech recognition technology.

PMID- 23155953
TI  - Psychiatric co-morbidity: revisiting the "mind-body" connection.

PMID- 23155954
TI  - Serum lipids, proteins and electrolyte profiles in rats following total body
      irradiation.
AB  - OBJECTIVE: Serum lipid and electrolyte imbalances are common in critically ill
      patients undergoing radiation therapy. Although multiple disease states and
      medication may be responsible for the development of these disorders, the aim of
      this research is to sequentially document the effect of total body radiation on
      body function utilizing the sequential changes in the serum lipids, electrolytes
      and protein in rats. METHODS: Serum protein and lipids contents were assessed
      using kits while electrolytes were assessed with flame photometry in rats exposed
      to total body irradiations of 1.27 Gy/min in cumulative doses to the fourth
      irradiation at five-day intervals. RESULTS: Total cholesterol and
      triacylglycerols serum levels were significantly reduced by irradiation (p <
      0.05). No significant differences between experimental and control groups for HDL
      C serum levels were detected. Serum electrolyte concentration remained within the
      normal range after each total body irradiation. Sodium, bicarbonate and chloride
      were significantly (p < 0.05) higher than control while potassium and creatinine
      were significantly reduced after the first irradiation only. Sodium/potassium
      ratio was significantly (p < 0.05) elevated. Serum protein was significantly (p <
      0.05) elevated with increasing radiation. CONCLUSION: There are subtle but
      significant changes in serum lipids, electrolytes and protein after total body
      irradiation of normal rats. These variations could be due to non-specific stress
      reactions; as such, they are important markers in radiation induced injury
      diagnosis.

PMID- 23155955
TI  - Elevated ferric, calcium and magnesium ions in the brain induce protein
      aggregation in brain mitochondria.
AB  - OBJECTIVE: Alzheimer's disease and Parkinson's disease are two of several
      neurodegenerative disorders that affect the elderly. Although their aetiology
      remains uncertain, studies suggest that elevated aluminium or other metal ions in
      the brain directly influence the development of the histological abnormalities
      normally associated with these diseases; other investigations suggest that metal
      ion-induced-dysfunction of mitochondria might be a critical factor. METHODS: In
      this study, the impact of elevated aluminum (Al3+), ferric (Fe3+), calcium (Ca2+)
      and magnesium (Mg2+) ions on brain histology and on the protein composition of
      brain mitochondria were evaluated. Rabbits were injected intra-cerebrally with
      1.4% solutions of either aluminium chloride (AlCl3), ferric chloride (FeCl3),
      calcium chloride (CaCl2) or magnesium chloride (MgCl2) and sacrificed 10 days
      later RESULTS: Histological analysis revealed that Al3+ but not the other ions
      induced neurofibrillary degeneration within the midbrain and medulla.
      Alternatively, SDS-PAGE revealed that Fe3+, Ca2+ and Mg2+ but not Al3+ induced
      alterations to the distribution of brain mitochondrial proteins. Both Fe3+ and
      Ca2+ triggered decreased concentration of three low molecular weight proteins (-7
      14 kd) but Ca2+ precipitated their total absence. Both ions led to increased
      concentration of a high molecular weight protein (-110 kd). In contrast, Mg2 led
      to the total absence of the protein of lowest molecular weight (-7 kd) and
      increased concentration of a -36 kd protein. CONCLUSION: These results suggest
      that elevation of some metal ions in the brain induces protein aggregation with
      the nature of the aggregation being highly ion dependent. The results also point
      toward major differences between the histopathological effect of Al3+ and other
      ions.

PMID- 23155956
TI  - Effect of gabapentin on postoperative pain and operation complications: a
      randomized placebo controlled trial.
AB  - OBJECTIVE: Prevention and treatment of postoperative pain and operation
      complications such as nausea and vomiting are most important concerns in
      postoperative care. There are several mechanisms involved in postoperative pain.
      Gabapentin is a gamma aminobutyric acid analogue that is known as an
      anticonvulsant drug. This drug is tolerated well and has known effects on pain
      and anxiety. This study has compared the effect of gabapentin on postoperative
      pain, operation complications and haemodynamics. SUBJECTS AND METHODS: This
      randomized double blinded placebo controlled clinical trial was conducted on 61
      patients divided randomly into two groups (30 as cases and 31 as controls). All
      patients had total abdominal hysterectomy. In the first group, the patients got
      100 mg gabapentin in the night and 300 mg gabapentin orally (one capsule) two
      hours before surgery. The second group got one capsule of multivitamin orally.
      Then all patients were subjected to the same anaesthesia protocol and total
      abdominal hysterectomy. During the 24 hours after operation, the patients were
      assessed according to pain, nausea, vomiting, dizziness, systolic blood pressure
      (SBP), diastolic blood pressure (DBP), pulse rate (PR) and morphine use at 1, 6,
      12 and 24 hours. RESULTS: Mean age and weight of patients were 45.86 +/- 4.06,
      48.16 +/- 4.48, 64.56 +/- 13.29 and 68.8 +/- 12.88 in the study population and
      control groups, respectively. Except in the first hour after operation (p =
      0.02), there was no significant differences between the two groups in morphine
      use. There was no significant correlation between the groups according to
      postoperative complications and the haemodynamic parameters (PR, SBP and DBP).
      CONCLUSION: Results show that gabapentin can decrease the need for morphine use
      in the first hour after operation only and has no significant effect on operation
      complications. Thus, we suggest gabapentin for pain management, and not to
      decrease opium use.

PMID- 23155957
TI  - Adequacy of lymph node harvesting in colorectal cancer management: improving
      standards, ensuring quality.
AB  - OBJECTIVE: The aim of this study was to determine the adequacy of nodal sampling
      in resection specimens for colorectal carcinoma in a Jamaican population.
      METHODS: The pathology records of all patients who underwent operation for
      colorectal carcinoma at the University Hospital of the West Indies (UHWI) during
      the five-year period, 2003-2007, were reviewed. Pertinent clinical and pathologic
      data were obtained and analysed. RESULTS: One hundred and ninety-one patients
      were identified with M:F ratio of 1.1:1 and a mean age of 66 years. There were
      119 (63%) left-sided lesions and 70 (37%) right-sided lesions. Stage T3N0 lesions
      were the most common and accounted for 41.1% of cases. The predominant histologic
      type was adenocarcinoma (99.5%) with the majority being moderately
      differentiated. The mean number of nodes sampled in node-negative cases was 13.8
      +/- 9.75 nodes for right-sided lesions and 10.64 +/- 7.25 nodes for left-sided
      lesions (p = 0.05, CI 95%). The adequacy of nodal sampling was acceptable in
      cases of N0 right-sided carcinomas but was unsatisfactory in cases of N0 left
      sided carcinomas. More importantly, however in two cases from the right and 10
      cases from the left, two or fewer nodes were harvested. CONCLUSION: This review
      suggests the need for re-examination of the adequacy of surgical resection and/or
      nodal sampling technique for colorectal cancer resection specimens, given the
      importance of nodal status in determining the need for adjuvant therapy. Less
      than adequate node sampling should not be accepted by the reporting pathologist
      or attending surgeon as this has important prognostic implications.

PMID- 23155958
TI  - To study the correlation between carrier status of nasal Staphylococcus aureus in
      patients on haemodialysis with hepatitis C, hepatitis B and their
      sociodemographic features.
AB  - AIM: To study the correlation of nasal Staphylococcus aureus carrier status in
      patients on haemodialysis, infected by hepatitis C virus (HCV), hepatitis B virus
      (HBV), and their sociodemographic features. SUBJECTS AND METHODS: A survey,
      including patients' sociodemographic features, was applied to patients by
      physicians in face to face interviews. Medical records regarding their serologic
      data were recorded from haemodialysis centres. Nasal swab samples of 2 cm depth
      from both nostrils of patients were obtained for nasal culture. Samples were
      inoculated in 5% sheep blood agar and incubated in an incubator at a temperature
      of 37 degrees C for 24 hours. The results were studied by the same
      microbiologist. RESULTS: A total of 185 patients were enrolled in the study.
      According to culture results, 14.1% of patients (n = 26) had methicillin
      sensitive Staphylococcus aureus (MSSA) and 1.1% (n = 2) had methicillin resistant
      Staphylococcus aureus (MRSA). Status of viral hepatitis was 3.8% (n = 8), 10.8%
      (n = 20) for HBV and HCV respectively. Forty per cent (n = 8) of patients with
      HBV (+) had MSSA carrier status. Statistically significant positive correlation
      between MSSA and HCV carrier was detected (r = 0.325, p = 0.001) but not between
      HBV carrier and MSSA (p = 0.255). CONCLUSION: In the present study, significant
      positivity was detected between MSSA carrier status and HCV in patients on
      haemodialysis and who have lived together with < or = 2 family members at home.
      Particularly, statistically significant correlation between HCV(+) and MSSA
      carrier was observed.

PMID- 23155959
TI  - A severe pneumonia due to methicillin resistant staphylococcus aureus clone USA
      300: implications of vertical transmission.
AB  - Staphylococcus aureus is an important pathogen in both community and healthcare
      associated pneumonia. We describe a case of severe pneumonia caused by the
      methicillin resistant Staphylococcus aureus (MRSA) clone USA 300 in a 44-year old
      post-partum woman and the subsequent vertical transmission of this virulent
      organism to her neonate.

PMID- 23155960
TI  - Images and diagnoses. Haemorrhage into a pituitary macroadenoma. Hypothalamic
      harmatoma.

PMID- 23155961
TI  - Psychopathological evaluation of patients requesting cosmetic rhinoplasty: a
      review.
AB  - OBJECTIVE: The goal of this review is to discuss possible underlying
      psychopathological situations in patients requesting surgical cosmetic
      rhinoplasty operation and to examine potential problems that might arise.
      SUBJECTS AND METHODS: An extensive search was conducted through PubMed, Ambase
      and Psychlnfo by using related keywords in English, like "rhinoplasty and
      psychiatric comorbidities", "rhinoplasty and psychopathology". RESULTS: Patients
      who demand cosmetic rhinoplasty operation appealed to the surgeon since they
      wanted to feel better about themselves after the surgery. Indeed, some long-term
      studies determined that such a situation can take place at high rates. However,
      some studies reported the possibility of serious psychological disorders after
      such surgical operations. Studies relating to the analysis of psychopathologic
      symptoms are quite limited. Research has shown that psychopathologic evaluation
      conducted preoperatively is especially important to identify serious
      psychopathologies such as personality disorders and body dysmorphic disorder
      (BDD). CONCLUSIONS: Exclusion of patients possessing serious psychopathologies
      from operations provides better results in the long term. The lack of sufficient
      research in this area necessitates new and comprehensive studies.

PMID- 23155962
TI  - Prevalence of toxoplasmosis, cytomegalovirus and rubella IgG antibodies in Hatay
      women and children.
AB  - OBJECTIVE: Toxoplasmosis, cytomegalovirus and rubella may cause congenital
      infections. The aim of this study is to investigate toxoplasmosis,
      cytomegalovirus and rubella IgG antibodies in women and children who were
      admitted to the Hatay Women and Children Hospital between January 1 and December
      31, 2009. METHODS: Levels of IgG antibodies for toxoplasmosis, cytomegalovirus
      and rubella established with chemiluminescence immunoassay (Architect i2000,
      Abbott, USA) method were evaluated, retrospectively. RESULTS: The results were
      obtained from 1103 cases. Seropositivity of IgG antibodies for toxoplasmosis (n =
      743), cytomegalovirus (n = 929) and rubella (n = 746) were 59.9%, 98.9% and
      93.6%, respectively CONCLUSION: Routine serological screening should be
      recommended in women of childbearing age. Seronegative subjects should be
      vaccinated for rubella and educated for protection from toxoplasmosis.

PMID- 23155963
TI  - Endoscopic carpal tunnel release in Jamaica--seven years experience.
AB  - OBJECTIVE: To assess the patient profile and outcome of treatment, by endoscopic
      release, of patients with carpal tunnel syndrome. METHODS: A descriptive study
      was done using data from two sets of patients who had endoscopic carpal tunnel
      release in Jamaica from 2004 to 2006 and 2006 to 2010. The medical records of
      patients who had a diagnosis of carpal tunnel syndrome using symptoms, clinical
      signs and confirmation by nerve conduction test were reviewed. The data were
      analysed using SPSS and Micosoft Excel. RESULTS: A total of 68 patients with 75
      cases of carpal tunnel syndrome were done. Fifty-two (76%) of these patients were
      females and about 50% were older than 41 years old. There were 61 (90%)
      unilateral cases. Of these, the majority of cases affected the right hand. All
      patients had improvement in symptoms after one week, required minimal analgesic
      use, had good compliance with rehabilitation and returned to work after about two
      weeks. There were three cases of pilar tenderness, two cases of transient
      paraesthesia in the index finger which resolved after three weeks. There were
      three failed cases from the first series which had to be converted to open carpal
      tunnel release. The complication rate was 6.7%. No serious complications occurred
      in the second series and all were treated successfully without interventional
      surgery. The rate of conversion to open release was 4%. CONCLUSION: Carpal tunnel
      affects mostly middle aged females and when treatment is done by endoscopic
      release, there is a fast resolution of symptoms and early return to work.

PMID- 23155964
TI  - Sociodemographic determinants of complicated unsafe abortions in a semi-urban
      Nigerian town: a four-year review.
AB  - BACKGROUND: Abortions performed by persons lacking the requisite skills or in
      environments lacking minimal medical standards or both are considered unsafe. It
      is estimated that over 20 million unsafe abortions are performed annually and
      about 70 000 women die globally as a result, with the majority occurring in the
      developing world. This study aims to determine the sociodemographic factors
      involved in complicated unsafe abortions. SUBJECTS AND METHODS: The study is a
      four-year retrospective evaluation of all cases of complicated unsafe abortions
      managed at the Niger Delta University Teaching Hospital, Okolobiri, Bayelsa
      state, Nigeria between January 1, 2007 and December 31, 2010. RESULTS: The
      incidence of unsafe complicated abortions over the study period was 4.10% of
      total deliveries and contributed 14.0% of gynaecological admissions: 34.92%
      occurred in adolescents less than 20 years of age, of which the majority (55.55%)
      were secondary school students. There were 55.45% of patients who were
      nulliparae, 60.32% were unemployed and 69.80% were unmarried. A total of 87.30%
      had never used any form of contraceptive. Abortion mortality rate was 256/100 000
      deliveries and the case fatality was 4.76%. It constituted 30.0% of all
      gynaecological deaths and 17.64% of maternal deaths during the study period. The
      commonest cause of death was septicaemia (66.66%). CONCLUSION: Unfavourable
      sociodemographic factors are major determinants of the high incidence of unsafe
      abortion in the Niger Delta despite strict abortion laws. Concrete measures must
      be put in place to address these, as unsafe abortion and its complications are a
      major cause of maternal morbidity and mortality in the environment.

PMID- 23155965
TI  - The impact of a no-user-fee policy on the quality of patient care/service
      delivery in Jamaica.
AB  - This paper is a submission to the Sessional Select Committee on Human Resources
      and Social Development by the Medical Association of Jamaica on September 25,
      2011, and presented orally by both authors on October 20, 2011. It explores the
      impact of the no-user-fee policy on the quality of patient care/service delivery
      in Jamaica and makes recommendations for reform.

PMID- 23155966
TI  - Prevalence of dentine hypersensitivity among adult patients attending a dental
      hospital clinic in Turkey.
AB  - OBJECTIVES: The aim of this study is to determine the prevalence of dentine
      hypersensitivity (DH) and to examine some associated factors such as the
      initiating stimuli among adult patients attending the Restorative Clinic of the
      Kirikkale University Dental Faculty, Turkey. METHODS: Questionnaires for 1169
      patients, 678 men and 491 women, were completed and necessary clinical
      examinations performed during a one-year period and patients who were diagnosed
      with DH were questioned further about their occupation and smoking habits.
      Patients with at least two different quadrants which had sensitive teeth with
      sound exposed cervical dentine on the facial surface, were included in the study.
      The amount of cervical lesions, buccal gingival recession and initiating factors
      associated with the sensitive teeth were also recorded. RESULTS: Of the 1169
      patients examined, 89 were diagnosed as having dentine hypersensitivity, giving a
      prevalence of 7.6%. The commonest teeth affected were the upper premolars and the
      commonest initiating factor was cold drinks. CONCLUSIONS: The prevalence of
      dentine hypersensitivity in a postgraduate clinic in Turkey was 7.6%. The
      commonest teeth affected were the upper premolar and the commonest initiating
      factor was cold drinks.

PMID- 23155967
TI  - Orthodontic treatment need of children in Trinidad and Tobago.
AB  - OBJECTIVE: This prospective cross-sectional study was undertaken to determine the
      normative and perceived orthodontic treatment needs of children aged 11-12 years
      in a Caribbean country, Trinidad and Tobago. METHODS: One author, an experienced
      orthodontist, examined 367 children using the Dental Health Component (DHC) of
      the Index of Orthodontic Treatment Need (IOTN) to assess the normative need. The
      same orthodontist administered the questionnaire to assess the patient's
      perceived needs using the Aesthetic Component (AC) of the IOTN and the Oral
      Aesthetic Subjective Impact Scale (OASIS). RESULTS: The DHC and the AC of the
      IOTN and the OASIS showed respectively that 61.4%, 2.5% and 0.6% of the children
      had definite need for orthodontic treatment. The female proportion of the sample
      was more than the target population but the perceived need and normative need for
      orthodontic treatment did not depend significantly (p < 0.05) on the gender or
      ethnicity of the subjects of this study. The perception of need for orthodontic
      treatment differed inversely from the normative need and this is seen to be
      significant (p < 0.05) when OASIS was used. CONCLUSIONS: Approximately three out
      of five children in Trinidad and Tobago have a great (or very great) need for
      orthodontic treatment for dental health reasons.

PMID- 23155968
TI  - Dental anxiety among patients visiting a dental institute in Faridabad, India.
AB  - Despite advances in dentistry, anxiety about dental treatment and the fear of
      pain remains widespread among patients and is a significant barrier to dental
      treatment. This study would therefore provide information so as to minimize
      levels of anxiety and aid in planning stress-free treatment. The cross-sectional
      study utilizing a self-reported questionnaire based on Modified Corah's Dental
      Anxiety Scale (MDAS) framed in Hindi (local language) was performed on 1032
      patients (aged 14-68 years). Around 1004 questionnaires were returned (response
      rate--97.3%). Overall, prevalence of dental anxiety was high (50.2%), but severe
      anxiety (phobia) was low (4.38%). The prevalence of anxiety was seen mostly in
      the 20-30-year age group (37.3%). Anxiety was also seen to be significantly
      higher in females (mean - 11.79) than in males [mean - 9.47] (p < 0.0000).
      Patients anxious about dental procedures are often more difficult to treat.
      Anxious patients should be identified and managed appropriately by
      behavioural/pharmacological measures.

PMID- 23155969
TI  - Periodontal health knowledge and smoking are associated with periodontal
      treatment need according to tooth brushing levels.
AB  - OBJECTIVE: The aim of this study is to determine whether periodontal health
      knowledge is associated with frequency of tooth brushing and periodontal
      treatment need. METHODS: Four hundred and two subjects participated in the study.
      Data on sociodemographic variables (age, gender, marital status, income, and
      education), general health, smoking behaviour tooth cleaning habits and knowledge
      on periodontal health/disease were collected with a questionnaire. Periodontal
      treatment need was examined using the Community Periodontal Index of Treatment
      Needs (CPITN). According to the CPITN scores, the treatment needs were grouped as
      minimum (CPITN = 0), low-level (CPITN = 1-2), or high-level (CPITN = 3-4).
      RESULTS: Statistical differences were found between the frequency of tooth
      brushing and smoking status, marital status, periodontal health knowledge and
      periodontal treatment needs. Gender (females), place of residence (urban areas),
      education and periodontal health knowledge had positive relationship with tooth
      brushing frequency, while smoking and periodontal treatment need had negative
      relationship. When multivariate logistic regression analysis was applied, age,
      marriage and poor periodontal knowledge were associated with increased low-level
      periodontal treatment needs, and age, marriage and smoking were associated with
      increased high-level periodontal treatment need. CONCLUSION: In the limits of
      this study, we suggest that gender, smoking habits, marital status, place of
      residence, education and periodontal health knowledge are determining factors
      related to tooth brushing frequency. Periodontal knowledge and smoking are
      associated with periodontal treatment needs.

PMID- 23155970
TI  - Calabash pregnancy: a malingering response to infertility complicated by domestic
      violence.
AB  - This is a case report of a 20-year old para 0+0 who presented with an 11-month
      pregnancy. On evaluation, the pregnancy was found to be a fake made-up 'calabash
      pregnancy'. There were no pregnancy symptoms and she had just menstruated three
      weeks prior to presentation. This was a deliberate event in response to delayed
      pregnancy attainment complicated by domestic violence. Domestic violence was in
      the form of verbal and physical abuse and later was on a monthly basis
      precipitated by onset of her menstrual flow. The patient's age, monogamous union
      and the fact that she is an orphan made her vulnerable to domestic violence.

PMID- 23155971
TI  - Acute hepatitis C infection with unclear route of transmission.
AB  - A 43-year old man acquired acute hepatitis C virus (HCV) infection with unclear
      route of transmission. There were no known sexual or other risk factors for HCV
      acquisition. Phylogenetic analysis confirmed that the case was infected with
      identical genotype 1b strain. After symptomatic treatment for three weeks, the
      HCV was spontaneously cleared and liver function recovered.

PMID- 23155972
TI  - Simultaneous rupture of bilateral quadriceps tendon and rotator cuff tear: a case
      report.
AB  - This is a case report of a patient who sustained both a bilateral quadriceps
      tendon rupture and a complete rotator cuff tear. Overuse is a known risk factor
      for rotator cuff tears, but this case suggests that it can also be a risk factor
      for quadriceps tendon rupture.

PMID- 23155973
TI  - A report summarizing health problems in everyday life in Tokyo: the importance of
      discussion from various perspectives.

PMID- 23155974
TI  - Twenty-four hour trauma team at the University Hospital of the West Indies,
      Kingston, Jamaica--the time is now.

PMID- 23155975
TI  - The effect of serum magnesium levels and serum endothelin-1 levels on bone
      mineral density in protein energy malnutrition.
AB  - An inadequate and imbalanced intake of protein and energy results in protein
      energy malnutrition (PEM). It is known that bone mineral density and serum
      magnesium levels are low in malnourished children. However, the roles of serum
      magnesium and endothelin-1 (ET-1) levels in the pathophysiology of bone
      mineralization are obscure. Thus, the relationships between serum magnesium and
      ET-1 levels and the changes in bone mineral density were investigated in this
      study. There was a total of 32 subjects, 25 of them had PEM and seven were
      controls. While mean serum ET-1 levels of the children with kwashiorkor and
      marasmus showed no statistically significant difference, mean serum ET-1 levels
      of both groups were significantly higher than that of the control group. Serum
      magnesium levels were lower than normal value in 9 (36%) of 25 malnourished
      children. Malnourished children included in this study were divided into two
      subgroups according to their serum magnesium levels. While mean serum ET-1 levels
      in the group with low magnesium levels were significantly higher than that of the
      group with normal magnesium levels (p < 0.05), mean bone mineral density and bone
      mineral content levels were significantly lower (p < 0.05). In conclusion, many
      factors play a role in the pathophysiology of changes in bone mineral density in
      malnutrition. Our study suggested that lower magnesium levels and higher ET-1
      levels might be important factors in changes of bone mineral density in
      malnutrition. We recommend that the malnourished patients, especially with
      hypomagnesaemia, should be treated with magnesium early.

PMID- 23155976
TI  - Family history of diabetes and parental consanguinity: important risk for
      impaired fasting glucose in south east Asians.
AB  - OBJECTIVE: Offsprings of type 2 diabetics have increased risk of metabolic
      disturbances. The aim of the study is to assess the potential effect of family
      history of type 2 diabetes (FHD) and parental consanguinity on fasting plasma
      glucose (FPG) levels. SUBJECTS AND METHODS: Non-diabetic offsprings of one or
      both parents with type 2 diabetes and healthy controls of comparable age, without
      a FHD were the subjects of this study. Family history of type 2 diabetes was
      defined by the presence of type 2 diabetes in one or both parents of the subject.
      Consanguinity was defined as history of marriage with a first cousin. Fasting
      plasma glucose levels were determined in cases and controls. RESULTS:
      Impairedfasting glucose (IFG) was identified in 42% of subjects with FHD and in
      14% without FHD. We found a strong independent association of FHD with impaired
      fasting glucose in both males and females by logistic regression analysis after
      adjusting the data for age, gender and body mass index (BMI). Parental
      consanguinity modifies the effect of FHD on IFG. CONCLUSION: We concluded that
      family history of diabetes and parental history of consanguinity determine the
      risk for impaired fasting glucose in this study population.

PMID- 23155977
TI  - The role of pre-induction ketamine in the management of postoperative pain in
      patients undergoing elective gynaecological surgery at the University Hospital of
      the West Indies.
AB  - OBJECTIVES: To determine if a single preoperative dose of ketamine hydrochloride
      reduces the narcotic analgesic requirements and/or pain scores reported by
      patients in the first 24 hours postoperatively. METHODS: A single-centred,
      prospective, case-control study was conducted on 84 patients aged 18-65 years,
      American Society of Anaesthesiologists (ASA) I and II, undergoing elective
      gynaecological procedures at the University Hospital of the West Indies (UHWI).
      Patients were randomly assigned to one of two treatment groups: (a) ketamine
      group, where patients received intravenous ketamine 0.15 mg/kg pre-induction of
      anaesthesia; and (b) placebo group, patients received normal saline. The
      anaesthetic technique was standardized. Postoperatively, patients were
      interviewed at 15-minute intervals for the first hour then at 2, 4, 6, and 24
      hours to determine their pain scores and any side effects. Timing and dose of
      opioid analgesics were also recorded. RESULTS: The mean cumulative morphine dose
      over the first 24 hours postoperatively was 29.6 +/- 10.8 mg for the ketamine
      group and 31.9 +/- 11.2 mg for the placebo group (p = 0.324). There was also no
      significant difference in pain intensity measured by the visual analogue scale
      (VAS) between the groups. Patient age and the type of surgery performed were not
      found to influence pain intensity. The most common adverse effects were nausea
      and vomiting (32.5%), dizziness (42.2%), drowsiness and sedation (45.8%) with no
      significant difference between groups. Both groups had an average in-hospital
      stay of three days postoperatively, however, the patients in the ketamine group
      reported higher satisfaction scores than those in the placebo group (p = 0.039).
      CONCLUSION: Despite no significant reduction in postoperative narcotic
      requirements or pain intensity, more patients who received ketamine reported
      higher levels of satisfaction with their pain management.

PMID- 23155978
TI  - Correlation of cataract with serum lipids, glucose and antioxidant activities: a
      case-control study.
AB  - OBJECTIVE: The aim of this study is to evaluate the relationship between cataract
      development and serum lipids, glucose as well as antioxidants in a case-control
      study. METHODS: Ninety patients with cataract and 90 age- and sex-matched healthy
      controls were investigated. Lipid profiles including triglyceride (Tg), total
      serum cholesterol (Chol) and cholesterol content in high-density lipoproteins
      (HDL chol) and low-density lipoproteins (LDL chol) as well as fasting glucose
      (FBS) were measured for all subjects. Plasma oxidative stress as thiobarbituric
      acid-reactive substances (TBARS) and the status of antioxidants were studied as
      ferric reducing/antioxidant power (FRAP) and thiol substance assay. RESULTS: A
      higher prevalence of abnormal FBS (8.9 vs. 1.1%), Tg (26.7 vs. 8.9%) and Chol
      (54.4 vs. 30%) was found in cataract patients than the control group (p < 0.05).
      Plasma Tg (p = 0.02), Chol (p = 0.001) and LDL chol (p = 0.04) were significantly
      higher in the cataract group than in the control group. Likewise TBARS (p = 0.05)
      as the level of oxidative stress was significantly higher in the case group, and
      FRAP (p = 0.03) and thiol (p = 0.02) assays as the antioxidant activity was
      significantly lower among cataract patients. CONCLUSION: This study has shown
      that hypercholesterolaemia, hypertriglyceridaemia, high LDL chol and high FBS are
      associated with cataract. Also lower plasma antioxidant levels and higher levels
      of oxidative stress were seen in cataract patients than healthy controls. These
      findings indicate a need for health promotional activities aimed at controlling
      these preventable factors among high risk populations.

PMID- 23155979
TI  - Expression of low molecular weight proteins in patients with leukaemia.
AB  - The current study is conducted to observe the differences in the level of low
      molecular weight proteins in the sera of patients with leukaemia in comparison to
      healthy subjects (control group). The sera of patients with leukaemia showed 15
      peaks in the densitometric curve in comparison to the seven peaks of the
      controls. The peaks in the experimental samples that coincide with those in the
      control were of 134.14, 113.15, 76.06, 63.25, 48.07, 22.85 and 16.47 kDa
      molecular weights, respectively. Most of the new peaks appeared between the
      proteins of molecular weight 36-29 kDa in the experimental groups. Mean density
      of the 134.14 kDa protein band showed an increase in the protein in experimental
      groups I and II only whereas 113.15 and 22.85 kDa protein were increased in all
      experimental groups of patients with leukaemia. The expression of 76.06 and 63.25
      kDa protein fraction was downregulated in the patients with leukaemia. A decline
      in the level of the protein of 48.07 kDa was observed in patients with leukaemia
      except in group I. Unlike the other protein fractions, the level of the protein
      of 16.47 kDa was significantly (p < 0.05) increased with a maximum density in
      group II. Intergroup experimental) comparison revealed an increasing pattern of
      95.44 and 89.21 kDa with maximum level in group III sera. However the protein
      fractions of 38.07 and 34.94 kDa varied in the serum with maximum density in
      Group IV Protein fractions of 32.92 and 31.24 kDa were expressed in all age
      groups of patients with leukaemia with a maximum density in group III whereas the
      percentage densities of 14.42 and 13.56 kDa protein were quite different. This
      preliminary study will provide a basis to study the role of different proteins in
      patients with leukaemia.

PMID- 23155980
TI  - Comparison of urine analysis using manual and sedimentation methods.
AB  - OBJECTIVE: Microscopic examination of urine sediment is an essential part in the
      evaluation of renal and urinary tract diseases. Traditionally, urine sediments
      are assessed by microscopic examination of centrifuged urine. However the current
      method used by the Georgetown Public Hospital Corporation Medical Laboratory
      involves uncentrifuged urine. To encourage high level of care, the results
      provided to the physician must be accurate and reliable for proper diagnosis. The
      aim of this study is to determine whether the centrifuge method is more
      clinically significant than the uncentrifuged method. METHODS: In this study, a
      comparison between the results obtained from centrifuged and uncentrifuged
      methods were performed. A total of 167 urine samples were randomly collected and
      analysed during the period April-May 2010 at the Medical Laboratory, Georgetown
      Public Hospital Corporation. The urine samples were first analysed
      microscopically by the uncentrifuged, and then by the centrifuged method. The
      results obtained from both methods were recorded in a log book. These results
      were then entered into a database created in Microsoft Excel, and analysed for
      differences and similarities using this application. Analysis was further done in
      SPSS software to compare the results using Pearson ' correlation. RESULTS: When
      compared using Pearson's correlation coefficient analysis, both methods showed a
      good correlation between urinary sediments with the exception of white bloods
      cells. The centrifuged method had a slightly higher identification rate for all
      of the parameters. CONCLUSIONS: There is substantial agreement between the
      centrifuged and uncentrifuged methods. However the uncentrifuged method provides
      for a rapid turnaround time.

PMID- 23155981
TI  - Management of breast abscesses in Jamaican women is there need for a paradigm
      shift?
AB  - A paradigm shift from operative to non-operative management of breast abscesses
      has occurred in surgical centres worldwide. The recent experience in managing
      these patients at the University Hospital of the West Indies (UHWI) was examined.
      Data were obtained retrospectively from dockets retrieved from the UHWI medical
      records department, and were analysed using the SPSS version 11.0 software
      package for Windows. Seventy-seven patients with breast abscesses presented
      during the 66-month study period, but complete data were unavailable for
      seventeen cases. The mean age of the remaining sixty patients was 32 years. There
      was one male patient. There were no cases of bilateral disease, and the majority
      was right-sided. Mean white blood cell count at presentation was mildly elevated
      at 11.9 x 10(9)/L, and had no relationship to method of management or length of
      stay. There were two cases treated with aspiration and antibiotics only. All
      other cases were treated with incision and drainage. Culture results were
      available in forty-four cases, and in 80%, Staphylococcus aureus was identified,
      with one case of methicillin resistant Staphylococcus aureus. The mean delay to
      the operating theatre was one day after presentation and the mean length of stay
      was 4.5 days. Seventeen patients had a 'non-cosmetic' incision. The traditional
      management of breast abscess provides challenges in terms of delay to the
      operating theatre and prolonged hospital stays. There is increased expense, as
      well as loss of productive work hours, associated with this line of treatment.
      Non-operative management has not traditionally been undertaken in our
      institution, but it is documented elsewhere to be safe, practical, and results in
      improved cosmetic outcomes. Prospective protocol-based trials are necessary to
      identify the patients most suitable for this line of management in a setting with
      limited resources.

PMID- 23155982
TI  - Establishing the Jamaica lupus registry: report of patients with systemic lupus
      erythematosus attending a major referral hospital in Jamaica.
AB  - BACKGROUND: Systemic lupus erythematosus (SLE) is an autoimmune disorder
      characterized by multisystem microvascular inflammation with the generation of
      autoantibodies. There are reports on demographic data and clinical manifestation
      of lupus in the United States of America and some other developed countries.
      There is a single study that has reported on the clinical and immunological
      features of SLE patients in Jamaica and another that reported that the prevalence
      of SLE in Jamaica was 5-17/100,000 in 1979. METHOD: A Jamaican lupus registry was
      established in 2008 at the Department of Medicine, The University of the West
      Indies. Data were collected using patient records and interview of patients
      fulfilling the American College of Rheumatology revised diagnostic criteria for
      SLE. Information on demographics, presence of diagnostic criteria for SLE,
      presence of complications and other clinical parameters were collected. RESULTS:
      There were a total of 107 patients that met the criteria for diagnosis of SLE at
      the referral centre, 96.3% of them female. Positive ANA (90.7%), arthritis
      (70.0%), malar rash (53.5%) and a positive dsDNA (40.1%) were the more frequent
      manifestations and diagnostic indices of the disease. Up to 41.7% of the SLE
      population suffered some form of complication. CONCLUSIONS: The initiation of a
      lupus registry has allowed for reporting ofpreliminary demographic, clinical and
      serological data and identifying of disease burden.

PMID- 23155983
TI  - The establishment of an intracranial tumour registry at the University Hospital
      of the West Indies.
AB  - In March 2010, the first intracranial tumour registry (ITR) in the English
      speaking Caribbean was started at the University Hospital of the West Indies
      (UHWI). This was deemed necessary as the already established Jamaica Cancer
      Registry only reports on malignant brain tumours. The ITR will collect data on
      all prospective intracranial tumours, benign and malignant, which are diagnosed
      histologically at the UHWI. Retrospective information dating back five years was
      also collected. Data collected so far reveal that between the years 2006 to 2010,
      a total of 317 cases were entered into the database. Of these, only 45 cases were
      considered eligible. The issues surrounding this discrepancy are discussed in
      this paper along with the many challenges experienced in the establishment of the
      ITR. From these experiences, the authors have also put forward several
      recommendations that may be useful to other researchers who wish to implement
      similar systems.

PMID- 23155984
TI  - The impact of the healthcare system in Barbados (provision of health insurance
      and the benefit service scheme) on the use of herbal remedies by Christian
      churchgoers.
AB  - AIM: To determine the impact of health insurance and the government's Benefit
      Service Scheme, a system that provides free drugs to treat mostly chronic
      illnesses to persons aged 16 to 65 years, on the use of herbal remedies by
      Christian churchgoers in Barbados. METHODS: The eleven parishes of Barbados were
      sampled over a six-week period using a survey instrument developed and tested
      over a four-week period prior to administration. Persons were asked to
      participate and after written informed consent, they were interviewed by the
      research team. The data were analysed by the use of IBM SPSS version 19. The data
      were all nominal, so descriptive statistics including counts, the frequencies,
      odds ratios and percentages were calculated. RESULTS: More than half of the
      participants (59.2%) were female, a little less than a third (29.9%) were male,
      and one tenth of the participants (10.9%) did not indicate their gender The
      majority of the participants were between the ages of 41 and 70 years, with the
      age range of 51-60 years comprising 26.1% of the sample interviewed. Almost all
      of the participants were born in Barbados (92.5%). Approximately 33% of the
      respondents indicated that they used herbal remedies to treat various ailments
      including chronic conditions. The odds ratio of persons using herbal remedies and
      having health insurance to persons not using herbal remedies and having health
      insurance is 1.01 (95% CI 0.621, 1.632). There was an increase in the numbers of
      respondents using herbal remedies as age increased. This trend continued until
      the age group 71-80 years which showed a reduction in the use of herbal remedies,
      32.6% of respondents compared with 38.3% of respondents in the 61-70-year
      category. CONCLUSIONS: The data demonstrated that only a third of the study
      population is using herbal remedies for ailments. Health insurance was not an
      indicator neither did it influence the use of herbal remedies by respondents. The
      use of herbal remedies may not be associated with affluence. The reduction in the
      use of herbal remedies in the age group 71-80 years could be due to primarily a
      lower response rate from this age group, and secondarily due to the Benefit
      Service Scheme offering free medication to persons who have passed the age of 65
      years.

PMID- 23155985
TI  - From cannabis to the endocannabinoid system: refocussing attention on potential
      clinical benefits.
AB  - Cannabis sativa is one of the oldest herbal remedies known to man. Over the past
      four thousand years, it has been used for the treatment of numerous diseases but
      due to its psychoactive properties, its current medicinal usage is highly
      restricted. In this review, we seek to highlight advances made over the last
      forty years in the understanding of the mechanisms responsible for the effects of
      cannabis on the human body and how these can potentially be utilized in clinical
      practice. During this time, the primary active ingredients in cannabis have been
      isolated, specific cannabinoid receptors have been discovered and at least five
      endogenous cannabinoid neurotransmitters (endocannabinoids) have been identified.
      Together, these form the framework of a complex endocannabinoid signalling system
      that has widespread distribution in the body and plays a role in regulating
      numerous physiological processes within the body. Cannabinoid ligands are
      therefore thought to display considerable therapeutic potential and the drive to
      develop compounds that can be targeted to specific neuronal systems at low enough
      doses so as to eliminate cognitive side effects remains the 'holy grail' of
      endocannabinoid research.

PMID- 23155986
TI  - Preference of patient information leaflets over standard drug monographs by
      patients prescribed hydrochlorothiazide, nifedipine and enalapril.
AB  - Standard drug monographs (SDMs) have been described as deficient in providing
      information in a manner simplified enough for patient reading. The aim of this
      study was to design patient information leaflets for hydrochlorothiazide,
      nifedipine and enalapril with content indicated by patients as relevant and to
      evaluate them against the SDM. Patient information leaflet (PIL) for each drug
      was designed to contain information on name, use of drug, how it works, how it is
      to be taken, common side effects, storage, missed dose action, things to avoid
      and when to contact the physician. Appropriateness was assessed by 10 practising
      pharmacists. For each drug, 40 patients were recruited, of which 20 were given
      SDM and 20 PIL. The knowledge of each participant was examined before and after
      exposure to SDM or PIL, as well as opinion on ease of reading and attractiveness
      using Pearson s Chi-square analysis. The results showed that both SDM and PIL
      improved knowledge of common side effects when compared with responses before
      exposure (chi2 = 24.26 for SDM and 27.64 for PIL, p < 0.001) with no difference
      between the groups. Respondents receiving PILs were better able to recall "things
      to avoid" after exposure to PIL (chi2 =10.85, p < 0.001). After exposure to SDM
      or PIL, the respondents who received PIL were more aware of when to contact the
      physician, compared to the SDM group (chi2 = 8.41, p < 0.01). When compared with
      SDM, respondents receiving PIL were more likely to indicate that PIL was easy to
      read (chi2 = 20.00, p < 0.001), attractive (chi2 = 12.45, p < 0.001) and they
      were more likely to recommend distribution of their reading material to other
      patients (chi2 = 22.11, p < 0.001). We conclude that there is benefit in
      designing information leaflets that simplify language and medication information
      contained in SDMs, including better understanding of precautions to take while on
      medication and when to consult physicians.

PMID- 23155987
TI  - The origin and future of offshore medical schools in the Caribbean.
AB  - The Flexner Report of 1910 concluded that there were too many medical schools in
      the United States of America (U.S.A.). In the wake of this conclusion, Flexner
      recommended higher admission and graduation standards for medical schools, the
      expected impact being fewer medical schools and graduates. One unintended
      consequence of this recommendation was a male-only policy by some universities to
      accommodate the smaller numbers of males. There were privately owned medical
      schools, unaffiliated to any college or universities which were run primarily for
      profit. Degrees were usually obtained after only two years of study and
      laboratory and dissection exercises were not part of the training. The adoption
      of Flexner's recommendation resulted in medical education becoming more
      expensive; it also created opportunities for persons without the financial means
      or the matriculation requirements to find alternative training programmes among
      those "medical schools" which did not adopt Flexner's recommendations. This paper
      traces the further development of these "medical schools" to facilitate the need
      for more doctors in the context of global maldistribution of doctors which has
      resulted in many medically underserved areas, more so in developing countries
      (1).

PMID- 23155988
TI  - Nutritional markers in patients undergoing chronic haemodialysis in Jamaica.
AB  - OBJECTIVES: The main objective of the study is to assess the nutritional status
      in patients on chronic haemodialysis in Jamaica using the Subjective Global
      Assessment tool and to correlate this with measured serum nutritional biomarkers,
      and also to identify nutritional biomarkers that can be used to assess
      nutritional status of patients with end-stage renal disease (ESRD). SUBJECT AND
      METHODS: Two hundred and nine consecutive patients on haemodialysis were selected
      from dialysis centres in Kingston, the capital of Jamaica, St. Catherine and
      Manchester Jamaica. The nutritional status of each participant was assessed using
      the Subjective Global Assessment tool in an interview performed by the
      researcher. Serum albumin, blood urea nitrogen and creatinine, highly sensitive
      complement reactive protein (hsCRP) and total fasting cholesterol were determined
      from a single serum sample. Only patients with ESRD were selected. Patients with
      acute renal failure or those with ESRD who were admitted in the previous two
      weeks were excluded from the study. Informed consent was obtained prior to
      interview and obtaining blood samples. RESULTS: Of the total participants, 54.5%
      (n=114) were male and 45.5% (n=95) female. The mean age for males was 51.9 years
      and females 47.6 years. Diabetes was documented as the most common cause of
      chronic renal disease and was found in 29.7%, hypertension in 24.4% and chronic
      glomerulonephritis in 22% of the participants. Approximately 80% of the study
      population had moderate malnutrition. There was a significant association between
      moderate malnutrition and a diagnosis of ESRD secondary to diabetes mellitus, p =
      0.03. Being on haemodialysis for < or = six months was significantly associated
      with moderate malnutrition p = 0.002. Also associated with moderate malnutrition
      were presence of an arteriovenous (AV) fistula (p = 0.01), serum albumin of < 40
      g/L (OR 3.68, p = 0.001), pre-dialysis creatinine of <880 micromol/L (p = 0.02)
      and cholesterol < 3.9 mmol/L (p = 0.04). Highly sensitive complement reactive
      protein levels of >10 mg/L was associated with moderate malnutrition, though
      statistical significance was not met (p = 0.39). CONCLUSION: Factors associated
      with malnutrition in patients on dialysis were having ESRD secondary to diabetes
      mellitus, dialysis duration for < or = six months, low serum albumin, pre
      dialysis serum creatinine of 880 micromol/L, low total cholesterol and presence
      of AV fistula access.

PMID- 23155989
TI  - Living donor kidney transplantation: the donor profile in Trinidad and Tobago.
AB  - OBJECTIVE: The National Organ Transplant Unit (NOTU) of Trinidad and Tobago,
      first implemented in January 2006, was mandated to facilitate renal and corneal
      transplantation. Since then, 60 transplants have been performed utilizing living
      kidney donors. The aim of this study is to ascertain the typical donor profile
      and to highlight the safety involved with live kidney donation. SUBJECTS AND
      METHODS: This descriptive study utilized the medical records of 60 consecutive
      live kidney donors between the period January 2006 and May 2010. Donor
      information was recorded on Microsoft Excel spreadsheets and analysed using the
      Statistical Package for Social Sciences 12.0. RESULTS: Among the 60 donors, males
      and females were in equal proportions with a mean age of 35.0 (+/- 10.7) years; a
      mean body mass index (BMI) of 25.8 (+/- 4.2) kg/m2 and 48.3% were of East Indian
      decent. The majority of donors were related to the recipient (71.7%). At
      donation, the mean creatinine was 84.9 (+/- 17.7) micromol/L, average urine
      creatinine clearance, 1.83 (+/- 0.53) mL/s and mean 24 hour urine protein, 141.8
      (+/- 78.6) mg. There was a significant association between the BMI at donation
      and proteinuria one year after donation (p = 0.043). The average hospital stay
      was 5.0 (+/- 0.95) days with minimal postoperative complications. CONCLUSION: The
      typical live kidney donor in Trinidad and Tobago is a 35-year-old, slightly
      overweight male or female who is usually of East Indian decent, donating a kidney
      to a relative. Living kidney donation in this transplant unit is safe with
      minimal short-term complications.

PMID- 23155990
TI  - Report and viewpoint on the Vaccine Safety Conference, Tryall Club, Jamaica,
      January 3-7, 2011: cautionary tales and implications for the Caribbean.
AB  - This paper represents information obtained from a recent conference on
      vaccination safety and policy: Vaccine Safety: Evaluating the Science Conference,
      Tryall Club, Jamaica, January 3-7, 2011 and the author's viewpoint on the same.
      The first section represents a synopsis of recorded information and the second
      the author's view of Caribbean concerns related to the recorded information.

PMID- 23155991
TI  - Prosthetic reconstruction after surgical resection of fibrous dysplasia of the
      maxillary and palatine bone.
AB  - Fibrous dysplasia is a rare disorder of the bone. It is seen in two main forms of
      presentation: monostotic and the polyostotic. A case of monostotic fibrous
      dysplasia of the maxillary and palatine bones in a 22-year old man who received
      prosthetic reconstruction is presented with a review of the literature.

PMID- 23155992
TI  - A patient experiencing pseudoseizures: a case report.
AB  - Pseudoseizures are a relatively complex problem of unknown aetiology and
      prognosis. They can at times resemble genuine seizure attacks but they have no
      abnormal electroencephalograpic (EEG) activity. Understanding the patient's
      unique psychological background appears to be fundamental in managing seizure
      frequency. Pseudoseizures can be disruptive to a person's lifestyle, limiting
      their ability to function and progress in society, particularly when it comes to
      employment or social interaction. The case discussed involves a 59-year-old man
      who presents with what is believed to be seizure-related activity but through the
      course of clinical evaluation, this turned out to be pseudoseizures.

PMID- 23155993
TI  - Sjogren's syndrome: a case report and review of the literature.
AB  - The manifestations and complications of Sjogren's syndrome are important to know,
      and dentists can play an important role in the detection of this disease. This
      report highlights such a case.

PMID- 23155994
TI  - Train your people to take others' perspectives.

PMID- 23155995
TI  - The art of developing truly global leaders.

PMID- 23155996
TI  - Anniversaries are not to be wasted.

PMID- 23155997
TI  - Accelerate!
AB  - The old ways of setting and implementing strategy are failing us, writes the
      author of Leading Change, in part because we can no longer keep up with the pace
      of change. Organizational leaders are torn between trying to stay ahead of
      increasingly fierce competition and needing to deliver this year's results.
      Although traditional hierarchies and managerial processes--the components of a
      company's "operating system"--can meet the daily demands of running an
      enterprise, they are rarely equipped to identify important hazards quickly,
      formulate creative strategic initiatives nimbly, and implement them speedily. The
      solution Kotter offers is a second system--an agile, networklike structure--that
      operates in concert with the first to create a dual operating system. In such a
      system the hierarchy can hand off the pursuit of big strategic initiatives to the
      strategy network, freeing itself to focus on incremental changes to improve
      efficiency. The network is populated by employees from all levels of the
      organization, giving it organizational knowledge, relationships, credibility, and
      influence. It can Liberate information from silos with ease. It has a dynamic
      structure free of bureaucratic layers, permitting a level of individualism,
      creativity, and innovation beyond the reach of any hierarchy. The network's core
      is a guiding coalition that represents each level and department in the
      hierarchy, with a broad range of skills. Its drivers are members of a "volunteer
      army" who are energized by and committed to the coalition's vividly formulated,
      high-stakes vision and strategy. Kotter has helped eight organizations, public
      and private, build dual operating systems over the past three years. He predicts
      that such systems will lead to long-term success in the 21st century--for
      shareholders, customers, employees, and companies themselves.

PMID- 23155998
TI  - The management century.
AB  - In 1886, addressing the nascent American Society of Mechanical Engineers, Henry
      R. Towne proposed that "the management of works" be considered a modern art-
      thereby heralding the Management Century, when management as we know it came into
      being and shaped the world in which we work. Kiechel, a past editorial director
      of Harvard Business Publishing, elucidates the three eras that punctuate this
      period: the years leading up to World War II, during which scientific exactitude
      gave wings to a new managerial elite; the early postwar decades, managerialism's
      apogee of self-confidence and a time when wartime principles of strategy were
      adapted, sometimes ruthlessly, to the running of companies; and the 1980s to the
      present, years that saw fast-moving changes, disequilibrium, and a servitude to
      market forces but also ushered in globalism, unprecedented innovation, and
      heightened expectations about how workers are to be treated. Along the way he
      examines the contributions of thinkers such as Frederick Taylor, Elton Mayo,
      Peter Drucker, and Michael Porter. What lies ahead? Perhaps the biggest challenge
      facing the 21st-century company, Kiechel posits, is to truly free the spark of
      human imagination from the organization's tidal pull toward the status quo.
      There's almost always a better way, he concludes--and management will continue to
      seek it.

PMID- 23155999
TI  - Does management really work?
AB  - HBR's 90th anniversary is a sensible time to revisit a basic question: Are
      organizations more likely to succeed if they adopt good management practices? The
      answer may seem obvious to most HBR readers, but these three economists cast
      their net much wider than that. In a decadelong study of thousands of
      organizations in 20 countries, they and their interview teams assessed how well
      manufacturers, schools, and hospitals adhere to three management basics: targets,
      incentives, and monitoring. They found that huge numbers of companies follow none
      of those fundamentals, that adopting the basics yields big improvements in
      outcomes such as productivity and longevity, and that good nuts-and-bolts
      management at individual firms shapes national performance. At 14 textile
      manufacturers in India, for example, an intervention--involving free, high
      quality advice from a consultant who was on-site half-time for five months--cut
      defects by half, reduced inventory by 20%, and raised output by 10%. A control
      group saw no such gains. The authors' global data set suggests that implementing
      good management at schools and hospitals yields change more slowly than at
      manufacturers--but it does come eventually. And the macroeconomic potential--for
      incomes, productivity, and delivery of critically needed services--is huge. A
      call for "better management" may sound prosaic, but given the global payoffs,
      it's actually quite radical.

PMID- 23156000
TI  - Deal making 2.0: a guide to complex negotiations.
AB  - Most big deals--megamergers, major sales, infrastructure projects--are built on a
      series of smaller ones. Each component deal presents a tactical challenge, but
      sequencing the parts in a way that achieves the target outcome is a strategic
      challenge that can unfold over months or years. This process, which the authors
      call a negotiation campaign, must generally be conducted on several fronts, each
      involving multiple parties. A multifront campaign can be much more effective than
      direct negotiation. After failed talks between Longshoremen and the Pacific
      Maritime Association--a group of shippers and port operators--the PMA's president
      turned away from the bargaining table and embarked on a campaign to align member
      firms, the business community, the U.S. government, and the public around his
      target outcome: the deployment of new information technologies to help unclog
      busy ports. The result was an agreement that was ultimately mutually beneficial.
      Designing and executing a negotiation campaign involves identifying the relevant
      parties, grouping them into fronts according to shared interests, determining
      whether to combine fronts (if, for instance, doing so would unite your allies),
      and deciding which fronts to approach early on and which to engage only after
      you've made progress elsewhere. The deal between the PMA and the Longshoremen
      involved high stakes, but many small-scale deals--such as gaining approval for a
      new product--also play out on multiple fronts. Going straight to a key decision
      maker often makes sense, but in many cases a multifront campaign is the only way.

PMID- 23156001
TI  - A campaign strategy for your career.
AB  - Organizations are inherently political, and pretending they're not is just plain
      impractical. But strategizing like a politician to advance your career doesn't
      have to mean compromising your integrity. You can craft a campaign plan that
      actually gets results without making you feel soiled. So argues Clark, who has
      worked with top-tier politicians and business executives as they strive to
      achieve their goals. She recommends that in business, as in politics, aspiring
      leaders choose their career milestones from the get-go and plan precisely what
      reaching each one will demand. That means taking inventory of the skills you'll
      need to acquire and figuring out exactly where and how you'll develop them. The
      best career planners work backward on the calendar: They start with the end
      points and carefully mark, in reverse, all the steps along the way. Then they set
      out on the course, identifying influential people whose favor they need to win
      and getting specific about how to garner it. They use power maps to home in on
      the most influential individuals and groups, and they aren't shy about courting
      votes. "Being political" still sounds negative to many people in business, but
      learning how to play the game doesn't have to be a Machiavellian endeavor.
      Indeed, harming people in the process won't help you at all, but if you eschew
      the political process altogether, you'll only harm yourself.

PMID- 23156002
TI  - How hard should you push diversity?

PMID- 23156003
TI  - Spanking in the schools. Should teachers be allowed to paddle students?

PMID- 23156004
TI  - Don't trash these gene. "Junk" DNA may lead to valuable cures.

PMID- 23156005
TI  - This issue has attitude.

PMID- 23156006
TI  - A national voice rings loud.

PMID- 23156007
TI  - Protein requirements: time to re-evaluate Canadian recommendations.

PMID- 23156008
TI  - New flu shot policy raises concerns.

PMID- 23156009
TI  - Mental illness in the workplace costs billions.

PMID- 23156010
TI  - What's new in patient safety.

PMID- 23156011
TI  - Cumulative incidence and incidence rate.

PMID- 23156012
TI  - Extra. Extra. Opportunity is knocking. Will you answer?

PMID- 23156013
TI  - The care utilizing evidence initiative.

PMID- 23156014
TI  - More time for care. An innovative program more time transforms wards by reducing
      clutter and cutting time-wasting activities for nurses.

PMID- 23156015
TI  - Get on board with the research ethics review process.

PMID- 23156016
TI  - Unreported incidents, wellness program strategies.

PMID- 23156017
TI  - Fighting the good fight.

PMID- 23156018
TI  - Recognizing refugees as human beings.

PMID- 23156019
TI  - Anesthesia error results in death: verdict for $20 million cut to $4 million.
      Boudreaux v. Pettaway, 1100281 ALSC -- SO.3d -- (9/28/2012)-AL.

PMID- 23156020
TI  - Arbitration agreement signed by daughter with POA ruled unenforceable. Case on
      point: Ping v. Beverly Enterprises, Inc., 2010 SC 000558 DG--S.W.3d--(8/23/2012)
      KY.

PMID- 23156021
TI  - FL: Claims for injury released in suit in state 1: defendants-not named in
      release-sued in state 2. Berrios v. Orlando Regional Healthcare System, 5D11-3727
      FLCA5 (9/21/2012)-FL.

PMID- 23156022
TI  - MA: Failure to follow 'care plan': bones broken: appeals court reversed order to
      dismiss case. Pitts v. Wingate at Brighton, Inc., 82 Mass. App. Ct. 285,
      (7/26/2012)-MA.

PMID- 23156023
TI  - Over $2 million dollar award for death from delivery error affirmed. Case on
      point: Hatwood v. Hospital of Univ of Penn., 2012 PA Super 217 (10/5/2012)-PA.

PMID- 23156024
TI  - [Current state and trends in development of Russian radiologic equipment].

PMID- 23156025
TI  - [A modified radiation kilovoltmeter for X-ray diagnostic apparatuses].

PMID- 23156026
TI  - [Portable X-ray apparatuses for dentistry and maxillofacial surgery].

PMID- 23156027
TI  - [Calibration of thermoluminescent dosimeters used for measuring the effective
      dose in computer tomography].

PMID- 23156028
TI  - [Estimation of the operating life of an X-ray tube anod].

PMID- 23156030
TI  - [Solution of the X-ray topographic problem for a stereo pair of scanned images].

PMID- 23156029
TI  - [A matrix gallium-arsenide detector for roentgenoraphy].

PMID- 23156031
TI  - [Calculation of the radiation parameters of an X-ray apparatus from its
      spectrum].

PMID- 23156032
TI  - [Reduction of the radiation load in digital X-ray diagnosis].

PMID- 23156033
TI  - [Reduction of the working temperature of X-ray tube bearings].

PMID- 23156034
TI  - [Radiation load exerted by PARDUS portable dental X-ray apparatuses].

PMID- 23156035
TI  - [New requirements to the radiation protection in X-ray surgery].

PMID- 23156036
TI  - [Microfocus roentgenography: an innovative medical diagnostic technology].

PMID- 23156037
TI  - [Rapid analysis of suppositories by quantitative 1H NMR spectroscopy].
AB  - Rapid analysis of suppositories with ibuprofen and arbidol by quantitative 1H NMR
      spectroscopy was performed. Optimal conditions for the analysis were developed.
      The results are useful for design of rapid methods for quality control of
      suppositories with different components

PMID- 23156038
TI  - [Search for new types of raw materials for antibacterial drugs].
AB  - Antibacterial properties of the mycelium culture of Fomitopsis officinalis
      (Vill.: Fr.) Bondartsev et Singer were investigated. It was shown to be an
      additional source for production of antibacterial substances active against
      gramnegative bacteria. In the future, the use of Fomitopsis officinalis for
      production of antibacterial substances active against the pseudotuberculosis
      pathogen or pseudomonads is quite possible.

PMID- 23156039
TI  - [Expression of estrogen receptors beta and beta1 in tissue of human non-small
      cell lung cancer].
AB  - Comparability of the level and intensity of estrogen receptors beta (ERbeta)
      expression in non-small cell lung cancer tissue of 32 patients was analyzed by
      flow cytometry using various antibodies--to the total fraction of ERbeta (clone
      14C8) as well to the full-length ERbeta1 isoform (clone EMRO2). The differences
      in the ER expression indexes detected by anti-ERbeta or anti-ERbeta1 antibodies
      were revealed in some patients, but it had no influence on average indexes of the
      ERbeta expression in the patient groups investigated. It was confirmed by the
      findings on more frequent and more intensive expression of ERbeta in the non
      small cell lung cancer tissue of female patients vs. the males irrespective of
      antibody type - anti-ER/ or anti-ERbeta1. Therefore, in comparative analysis of
      ERbeta expression in the groups of the patients with different clinicomorphologic
      characteristics of the disease it is possible to use both the antibodies. For
      individual disease prognosis in the routine clinical practice it is recommended
      to use the antibodies to the total fraction of ERbeta, since there are individual
      differences between the ERbeta expression indexes revealing by various types of
      antibodies.

PMID- 23156040
TI  - [Increase of antibacterial therapy efficacy in chronic sepsis with cycloferon and
      reamberin combination].
AB  - The use of reamberin and cycloferon combination for increasing the antibacterial
      therapy efficacy in patients with chronic sepsis (CS) was studied. It was shown
      that the combination provided more rapid elimination of the CS exacerbation
      symptoms, normalization of the hematologic indices, bacteriemia eradication and
      reduction of the cytokine blood profile--normal serum levels of proinflammatory
      (IL-1beta, IL-2, IL-6 and TNF-alpha) and antiinflammatory (IL-4) cytokines. The
      findings allowed to considered the use of the reamberin and cycloferon
      combination in the treatment of patients with CS pathogenetically reasonable and
      clinically perspective for increasing the antibacterial therapy efficacy.

PMID- 23156041
TI  - [Impact of hypoxen therapy on postoperative course in gynecologic patients].
AB  - The aim of the study was to estimate the use of hypoxen (antihypoxant) during the
      early postoperative course in gynecologic patients. The patients were divided
      into two groups according to the treatment scheme. 339 patients of the control
      group were under the routine therapy after the laparatomic gynecologic
      operations. 52 patients were additionally treated with hypoxen (antioxidant) (the
      main group). The impact of hypoxen on the antioxidant system and lipid
      peroxidation and its preventive effect on prolongation of the postoperative pain
      syndrom were estimated. The results of the study showed that hypoxen inhibited
      lipid peroxidation and activated the antioxidant system in the postoperative
      patients vs. the control group. It was also observed that among the patients
      additionally treated with hypoxen the percentage of those with prolonged
      postoperative pains was statistically lower (p<0.05, chi2 test). It was concluded
      that hypoxen normalized lipid peroxidation and antioxidant system after abdominal
      gynecologic operations. The additional use of hypoxen in the routine therapy of
      the gynecologic patients prevented prolongation of the postoperative pain
      syndrom.

PMID- 23156043
TI  - [Hepatotropic therapy in treatment of liver injury].
AB  - At present, the conception of the use, efficacy and safety of hepatotropic agents
      in treatment of drug-induced liver injury, in particular due to antituberculosis
      drugs is not yet final, which is conditioned by extremely rare clinical trials on
      the subject adequate to the up-to-date principles of the conclusive medicine. The
      review presents data on the hepatotoxic effect of antituberculosis drugs,
      analysis and systematization of the data on the use of hepatotropic agents in
      liver injury induced by antituberculosis drugs, the principles and
      characteristics of their clinical use. The mechanism of action of remaxol, a new
      original hepatotropic agent and the indications of its use are discussed. The
      experimental findings on the remaxol ability to decrease the antituberculosis
      drug-induced liver injury through lowering the carbohydrate, albuminous and fatty
      degeneration and activating the organ reduction are presented. The clinical
      trials are evident of the most efficient action of remaxol on the signs of
      toxemia, as well as cytolysis and cholestasis, which along with its antiasthenic
      and antidepressant action allows to use remaxol as an universal hepatotropic
      agent in the treatment of diverse drug-induced liver injuries in both the
      therapeutic and prophylactic schemes.

PMID- 23156042
TI  - [Diagnostic and treatment patterns in management of male patients with
      nongonococcal urethritis: results of Russian multicentral cross-sectional study].
AB  - The aim of the study was to estimate the diagnostic and treatment patterns in the
      management of acute nongonococcal urethritis (NGU) in males in some cities of
      Russia. Retrospective cross-sectional study was conducted in 2009 in 5 centers of
      4 cities in the Central Part of Russia (Kaluga, Pskov, Smolensk - 2 centres and
      Tula). The data on the diagnostic and treatment approaches to the management of
      NGU in male subjects >16 years old were collected and analyzed with the use of
      specially designed case report forms. 556 cases of acute urethritis were analyzed
      during the study. The diagnosis of NGU was confirmed in 401 cases. The average
      age of the patients was 29.8 years (16-68 years). The following diagnostic
      methods were used in 95% of the cases: urethral smear microscopy (314/82.4%), C.
      trachomatis - PCR (113/29.7%), ELISA (155/40.7%); T. vaginalis - PCR (106/27.8%);
      U. urealyricum and M. hominis, respectively - bacteriology (140/36.7% and
      126/33.1%), PCR (110/28.9% and 108/28.3%); M. genitalium - PCR (110/28.9%). The
      treatment patterns included antimicrobials AMs alone in 60.3, and AMs + non-AMs
      in 37.8% of the cases. The most frequently prescribed AMs were azithromycin
      (27.5%), fluconazole (16.4%), doxycycline (13.6%), metronidazole (11.2%),
      ofloxacine (7.3%), ceftriaxone (4.4%), josamycin (4.2). According to the results
      use of the standard methods for NGU diagnosis was rather rare. The use of PCR for
      atypical pathogens was the following: C. trachomatis 29.7%, U. urealyticum 36.7%,
      M. hominis 28.9%, M. genitalium 28.3%. Doubtful culture methods were used for
      detection of U. urealyticum and M. hominis (36.7% and 33.1%). The AMs treatment
      in some cases was not in compliance with the up-to-date practical guidelines for
      STD and NGU.

PMID- 23156045
TI  - [Comparative analysis of modern approaches to risk estimation from artificially
      created nanoparticles and nanomaterials].
AB  - The article represents a review of modern approaches to problem of
      nanotechnologies and nanomaterials risk estimation for human health and
      environment that were elaborated in EU, USA and some international authorities.
      Submitted data suggests that there is a significant coincidence with approaches
      being developed and introduced in Russian Federation under the guidance of
      Rospotrebnadzor. Particularly criteria being used in Russian Federation and EU
      for classification of nanotechnologies and nanoindustry production are mainly
      similar. They include a) identification of nanomaterials in production, b)
      establishment of production disintegration possibility with concomitant migration
      of free nanoparticles, c) possibility of nanoparticles emission/migration both in
      normal conditions of utilization and in possible emergency conditions, d) degree
      of proximity of particular kind of production to it's consumer that means the
      possibility of exposition being from closely to zero (in conditions of
      unhabitated exploitation) up to approximately 100% (in case of medicine, food and
      cosmetics), e) biological examination of potential danger of nanomaterials
      according to current volume of scientific information. As applied to
      nanotechnology plants there are such criteria in use as a) nanomaterial
      identification, b) personnel exhibiting possibility, c) potential toxicity of
      stuff in aerosol nano-form, d) characteristics of biological action. Thus applied
      in Russia principles for nanomaterials safety estimation do not contradict to
      concepts of foreign authorities that builds up a possibility of said approaches
      harmonization to internationally recognized norms.

PMID- 23156044
TI  - [The analysis of international legislation in the field of regulation of
      functional foods claims].
AB  - It is known that manufacturers quite often put into foodstuff marking or
      advertisement the information about its beneficial action into the consumers
      health, i.e. about its functional qualities. However in Russian Federation the
      rules are regulated using of term "functional foods" doesn't established. In the
      review of legislation acts which are regulated of using claims in the foodstuff
      marking or advertisement in the different countries have been shown that claims
      concerning of energy and nutritional values of foods (beneficial nutrition
      claims) should be used in compliance with established rules without additional
      investigations. Food health claims referring to the reduction of disease risk and
      (or) functional foods claims for children must maintain in compliance with
      established procedure. Only claims that have scientific evidence about its
      beneficial for health could be recommended for approval. Thereupon insistent
      necessity in development, discussion and approval regulation in the field of
      using Claims concerning the functional qualities of foods (described rules of
      using beneficial nutrition claims and claims referring to the reduction of
      disease risk and to children's development and growth) in Russian Federation and
      United Customs Union (EurAsEU) are obvious.

PMID- 23156046
TI  - [Oxidative and hydrolytic deterioration of palm oil and fat products based on it
      under various conditions of storage and transportation].
AB  - Studies have been conducted on the effect of storage conditions for refined
      deodorized palm oil on the quality and safety: in containers made of ferrous
      metals (mild steel) at unregulated temperature, in sealed plastic bags at the
      temperature -20 degrees C in stainless steel under stratification of nitrogen at
      the temperature of 40+/-1 degrees C. The choice of the objects of study
      determined by the normative documents of the Russian Federation governing the
      transportation and storage of vegetable oils and fat products based on them. All
      samples of palm oil with peroxide value of 1,0 to 1,5 meq O2/kg indicated the
      presence of a weak foreign taste, is not peculiar impersonalfat, the samples with
      peroxide value above 1,5 meq O2/kg were observed pronounced off-flavors and odors
      characteristic of stale oil. Rancidity was observed in samples having peroxide
      value of 2,0 meq O2/kg or more. Free acid value and anizidin value for the
      studied period changed to a lesser extent, from 0,06 to 0,1 mg KOH/g and from 1,2
      to 1,4 respectively. It is proved that, transportation/storage of palm oil at the
      temperature above 50 degrees C without stratification of nitrogen greatly
      accelerates the process of oxidative damage. Based on these data we can recommend
      transportation/storage and management process with the least possible time of
      contact of melted palm oil with oxygen to produce high-quality final product
      (within 2-3 hours from the time of melting).

PMID- 23156047
TI  - [The morbidity dynamics of alimentary-associated diseases in children and
      adolescents in Northern administrative district of Moscow over a period of 2006
      2010].
AB  - Through socio-hygienic monitoring of the Northern administrative district of
      Moscow in 2006-2010 the study of nutritional status and morbidity rates for
      alimentary-associated diseases of the digestive tract, the endocrine system,
      cardiovascular diseases and obesity - was conducted in children (5-11 years old),
      adolescents (12-16 years old) and adult population. Over the last 5 years
      negative dynamics in morbidity rates for the illnesses related to malnutrition
      and nutritional status disturbances was shown in children and adolescents. Thus
      it was noted a considerable increase of alimentary-associated diseases among
      children (2,3 times more) and adolescents (2,1 times more). This applies
      especially to gastrointestinal diseases (gastritis, duodenitis, etc.) and obesity
      which prevalence increased over the last 5 years among children (under 5 years
      old) 2,4 times more; and 2,1 times more among teenagers. In children and
      adolescents from the district gastrointestinal diseases amount to 15,6%
      ofallnutrition-related diseases. The authors of the article emphasize that
      currently hygiene education of the population (including children and
      adolescents) must become a key tool in implementing the state policy in the area
      of healthy nutrition and in activities of the primary care health service to
      prevent nutritional disturbances and decrease the prevalence rate of alimentary
      associated diseases with special attention from nutritionists, dietarians, and
      hygienists.

PMID- 23156048
TI  - [Nutritional status in patients after gastrectomy due to gastric cancer].
AB  - Aim of the study was to evaluate nutritional status in patients after gastrectomy
      due to gastric cancer. METHODS: In 55 (26 males and 29 females) gastric cancer
      patients after gastrectomy body composition (bioimpedansometry method); resting
      energy expenditures and home actual nutrition (frequency analysis method) were
      evaluated. Blood levels of major nutrients and metabolites were assessed.
      RESULTS: Both men and women suffered from weight loss after gastrectomy (mean BMI
      was 19,8+/-4,7 kg/m2 in men and 20,5+/-1,9 in women). Higher BMI was positively
      correlated with age in women (R=0,45; p<0,03), but not in men, however there was
      no difference in mean age and mean time after gastrectomy between men and women.
      Mean body fat mass significantly decreased in men (7,4+/-5,0 kg) and in women
      (12,0+/-7,1 kg) in compare to normal values (18,2 and 22,5 correspondingly)
      (p<0,001). Resting energy expenditure variably decreased (for 13-53%) in half of
      the patients, mainly due to decrease in lipid oxidation rate. Mean daily energy
      intake was lower than normal in short-term (1359 kcal in period of 12 months) and
      long-term (1814 kcal in 1-5 years period) after gastrectomy, due to decrease
      consumption of proteins, carbohydrates and fat. Mean blood total protein,
      hemoglobin and hematocrit levels were lower than normal values in 40% of
      patients. CONCLUSION: In gastric cancer patients low BMI, low fat mass and energy
      consumption are observed even long period of time after gastrectomy. Dietary
      counseling and support are badly needed in patients short-term as well as long
      term period after gastrectomy in men and younger women.

PMID- 23156049
TI  - [Effect of diet enriched with selenium on the psycho-emotional and adaptive
      capacity of patients with cardiovascular diseases and obesity].
AB  - It was studied the effect of diet enriched with selenium on the clinical and
      biochemical status, psycho-emotional and adaptive capacity of the organism in
      patients with diseases of the cardiovascular system. We examined 59 patients with
      cardiovascular disease and obesity, treated for 3 weeks antiatherogenic reduced
      calorie diet. Of these 36 patients from the index group took on the back of
      ground diet selenium containing diet product (part of alimentotherapy). Patients
      underwent clinical examination, biochemical parameters and the availability of
      selenium were measured. To assess the adaptive capacity of the organism we used
      Program Apparatus Complex. Quality of life of patients, overall health, level of
      anxiety and the dynamics of mental processes were assessed using SAS procedures,
      Spielberger-Hanin anxiety test, Serdyuk Quality of Life Questionnaire,
      Kraepelin's counting test. The results indicate positive changes in clinical and
      biochemical status, availability of selenium, adaptive capacity, psycho-emotional
      state of patients with cardiovascular disease and obesity because of the diet
      enriched with organic form of selenium. We revealed increase in activity,
      improvement of overall health and cognitive functions, mood stabilization,
      reduction of anxiety and emotional lability. The main differences observed
      between the groups identified in the leveling of the anxiety radical in psycho
      emotional status of patients.

PMID- 23156050
TI  - [Role of alimentary factor in gastroesophageal reflux disease pathogenesis and
      treatment].
AB  - The aim of the study was to evaluate the impact of meal volume, weight change,
      excessive weight, and caloric content of the ration on disease's manifestation
      and progression from data presented in the published scientific literature.
      Systematic review in PubMed/Medline databased was performed with key words: food,
      dietary patterns, nutrients, nutrition, meal volume, calorie in combination with
      gastroesophageal reflux and GERD. 113 articles were found and 29 of them were
      selected according to the following criteria: the article should contain data of
      clinical observations, or to be a result of meta-analysis; study group
      characteristic, study design, and results should have been available for the
      analysis. The review contains data concerning influence of body mass index, its
      change; meal volume and caloric content of the ration on clinical manifestations
      of GERD. The dietotherapy recommendations for this illness include exclusion of
      overeating, limitation in use of high-caloric foods, increased protein content in
      diet, the adherence of 3-4 meals daily, with the last meal at 2-3 hours before
      sleep. However, the majority of the recommendations on the use of dietary
      nutrition is mainly based on the empiric experience, not on scientific data, and
      that doesn't allow to prepare reasonable recommendations for changing the diet of
      the patients with GERD. There is a need for prospective studies of influence of
      diet correction on course of the disease.

PMID- 23156052
TI  - [Digestive enzyme functionality in pathology of the gastrointestinal tract with
      intestinal microbiocenosis disorders].
AB  - A change pattern in enzyme release function of digestive glands exerts the
      organism as a whole. Dysfunctions of hydrolysis and intestinal malabsorption
      (secondary malabsorption syndrome) are the first step towards nutrition and
      metabolism processes abnormality and that can play a role in genesis of
      pathological conditions. Recent researches arouse clinicians interest in
      determination of biofluid enzyme activity in different physiological and abnormal
      cases. Intestinal infections are followed by dysbacteriosis and obvious
      alterations in the hydrolase levels in the blood, urine and motions because of
      the changes of functional status of the liver, renal and intestinal barriers in
      relation to increted digestive enzymes. This causes an unfavorable course of
      recovery with the development of postinfectious digestion disorders as a result
      of previous acute diarrhea. Future researches are necessary to elaborate
      appropriate remodeling of developed pathosis with the help of enzymotherapy and
      probiotic diet.

PMID- 23156051
TI  - [Modern concepts of gene polymorphisms, which regulate lipid metabolism].
AB  - This review discusses the present view on lipid metabolism regulation with
      emphasis on polymorphisms of key genes. Relying on the analysis of the
      literature, the blood lipid specter of carriers of the key genes allelic variants
      has been described. Therefore, reasonability of a more profound study of the
      influence of genetic polymorphisms on lipid metabolism regulation is
      substantiated. It is revealed, that the carriers of one of the abnormal alleles
      causes a higher risk for obesity and its associated complications. Polymorphic
      variants of the genes, that regulated lipid metabolism are widely presented in
      human population. It explains the big interest to studying of communication
      between dyslipidemia, adiposity and other pathologies with features of a
      genotype. However, abnormality of metabolic process and associated diseases in
      most cases represent multifactorial diseases. For today, the important problem
      for researchers still is a definition of a role of individual genetic features in
      development of pathological processes. The special attention in researches of
      last years is given to the genes, which products concern to leptin-melanokortin
      system of regulation of a energy metabolism; proteins-carriers lipid's blood
      fractions and cholesterol; and also the enzymes splitting lipids. Lipid
      metabolism is closely connected with an exchange of carbohydrates, especially a
      glucose metabolism. That is why genes mediating actions of insulin represent the
      greatest interest. Today, more than 400 genes are the potential candidates,
      capable to regulate lipid exchange. However, the further careful and extensive
      researches in this area are necessary.

PMID- 23156053
TI  - [Peculiarities of vitamin status in men and women with cardiovascular disease and
      obesity].
AB  - We explored the characteristics of the vitamin status in 471 patients with
      cardiovascular diseases, according to sex, and BMI values. All patients underwent
      examination of the system Nutritest-IP: studying their actual meals at home,
      determined anthropometric measurement, body composition, using biochemical
      methods evaluated the state of the protein, lipid and carbohydrate metabolism,
      the functional state of liver and biliary tract, hemostasis, vitamin provision.
      The results suggest a lack of availability of patients with vitamins C and B
      group. The number of patients with deficient serum beta-carotene increased
      proportional to body mass index. The concentration of beta-carotene decreased and
      vitamin E - increased in blood serum proportionally to increase the degree of
      obesity. Thus the availability of vitamins in the blood serum depends from sex
      and body mass index values of the patients. These data suggest that the rate of
      supply of vitamins are reliable markers to assess the adequacy of the diet
      consumed by the content of vitamins in people with normal body weight.
      Appraisingly the content of beta-carotene and vitamin E in the serum of patients
      it should be taken into account that they have overweight or obese, and
      abnormality of lipid spectrum of blood serum.

PMID- 23156054
TI  - [Vitamins in rat experimental diets].
AB  - A comparison of full semisynthetic diets used in different laboratories has shown
      that its vitamin content covers physiological requirements of rats in these
      micronutrients. The significant fluctuations in group B vitamin concentrations
      may take place when one uses brewer's yeast as a source of these vitamins. A
      preliminary assessment of vitamin content in brewer's yeasts is required in this
      case. An essential contribution of basic components in diet vitamin content must
      be taken in consideration when one creates a vitamin-deficient diet. Casein
      contains substantial amounts of group B vitamins and vitamin D. Therefore
      decontamination of casein from water and / or fat-soluble vitamins or the use of
      commercial purified casein is required. Vegetable oils are usually used as a
      fatty component of a diet and they simultaneously serve as an additional source
      of vitamin E. A choice of naturally containing vitamin E oil as a fat component
      of a diet is crucial for the creating an alimentary deficiency of vitamin E. The
      content of fat-soluble vitamins in the diet of control group (group of
      comparison) and vitamin level in the diet of experimental group of animals must
      be equivalent in investigations with modified (quality and quantitative) fat diet
      component. Caloric restriction by simple reducing of food without increasing the
      amount of vitamins to an adequate level is incorrect. With these considerations
      in mind proper attention to the equivalence of vitamin content in the diet of
      animals in experimental and control groups should be paid during experiments
      scheduling. Otherwise, the studies carried out under deficient or excessive
      intake of vitamins can lead to incorrect interpretation of the results and
      difficulties in their comparison with the data obtained under different
      conditions.

PMID- 23156055
TI  - [The mineral composition of the carbohydrate-electrolyte drinks, vitamin-mineral
      complexes and dietary supplements for athletes].
AB  - In the article analyzes the macro- and trace element composition of sports
      drinks, vitamin-mineral complexes and biologically active additives (BAA). The
      estimation of the mineral collection of these products compared with the
      recommended standards. Established mineral composition many of the carbohydrate
      electrolyte solutions, vitamin-mineral complexes and biologically active
      additives corresponds the physiology standards. However in some vitamin-mineral
      complexes and especially biologically active additives a number of minerals can
      be either unreasonably low or unreasonably high. Furthermore during labeling,
      mainly in the category D, a number of errors were revealed. Particularly there
      were lack of instructions about the number of declared ingredients, inaccuracies
      in the calculations of the daily requirement of mineral elements etc. Providing
      of an athlete organism with minerals should be carried out not only by
      carbohydrate-electrolyte solutions, vitamin-mineral complexes and specialized
      BAA, but mainly through basal ration. Utilising of carbohydrate-electrolyte
      solutions, vitamin-mineral complexes and biologically active additives can be
      justified only by the recommendations of experts. This is true not only in pro
      sports, but for the mass sports, as well as for individual physical training, in
      order to maintain physically fit.

PMID- 23156056
TI  - [To the 90th anniversary of State Sanitary Epidemiologic Service Formation in
      Russian Federation].
AB  - State Educational Institution of Higher Professional Training of the Ministry of
      Health Care and Social Development Foundation of Russian Sanitary Epidemiologic
      Service dates back to September, 15, 1922, when a Decree on Sanitary Institutions
      of the Republic was signed. Afterwards the institutions of Sanitary Epidemiologic
      Service were improved: foundation of State Sanitary Inspectorate (1933-1951),
      approval of new concept of the Service and intensification of State Sanitary
      Inspectorate (1951-1991), foundation of State Sanitary Epidemiologic Service,
      centralization of management and financing of the Service, formation of Sanitary
      Epidemiologic Legislation (1991-2004), further restructurization of Sanitary
      Epidemiologic Service in accordance with administrative changes in Russia (2004
      until now).

PMID- 23156057
TI  - [Problems of more healthy work conditions, occupational diseases prevention on
      enterprises of major economic branches].
AB  - The article deals with evaluation of contemporary work conditions in mining
      enterprises, iron industry, aluminium production plants. Work conditions are
      classified according to hazard level and jeopardy in various occupations within
      the enterprises. Reports presented by Russian Mining Metallurgy Trade-union on
      occupational morbidity over 2002-2010 were summarized. Occupational morbidity
      parameters were defined, their increase was identified, structure of occupational
      pathology was determined. The authors formulated suggestions in improving the
      work conditions, in occupational diseases prevention in mining enterprises, iron
      industry and aluminium production plants.

PMID- 23156058
TI  - [Influence of occupational factors in ore-dressing and processing enterprise on
      reproductive health of the female workers].
AB  - The authors present data on studies of work conditions of female workers engaged
      into ore-dressing and processing enterprise, occurrence of gynecologic diseases,
      and results of retrospective analysis of pregnancy and delivery course over 2001
      2010. Findings are that work conditions in the industry increase gynecologic
      diseases risk and complications rate during pregnancy and delivery.

PMID- 23156059
TI  - [Evidence-based medicine in evaluating occupational health risk in workers
      engaged into graphite ware production].
AB  - The article deals with results of epidemiologic study on evaluating the health
      state of workers engaged into graphite ware production, through three various
      parameters based on data about chronic non-occupational diseases. The authors
      evaluate carcinogenic risk for the population residing on various distances from
      the enterprise.

PMID- 23156060
TI  - [Immunopathogenetic features of occupational bronchitis].
AB  - The article based on research work covers functional, bronchoscopy, microbiologic
      and immunologic features of chronic dust bronchitis and chronic bronchitis caused
      by toxic chemicals.

PMID- 23156061
TI  - [Lipid metabolism in occupational chronic bronchitis associated with diabetes
      mellitus].
AB  - The study of 311 patients with chronic occupational bronchitis associated with
      diabetes mellitus (or diabetes-free) revealed lipid metabolism disorders
      presenting with overweight, obesity, dyslipoproteinemia. Diabetes mellitus
      addition to chronic bronchitis increased frequency of lipid metabolism disorders
      and higher values of lipid state. The revealed lipid metabolism disorders were
      more marked in the females.

PMID- 23156062
TI  - [Gender differences in death causes and survival rate of silicosis patients].
AB  - The authors analyzed structure of mortality and survival rate in 284 silicosis
      patients over 14 years. Findings are that the mortality structures among the
      females and the males with silicosis are different. In both groups compared, the
      first place among death causes was occupied by cardiovascular diseases. The
      females with silicosis were more frequent to die with broncho-pulmonary
      conditions, vs. the males of the same group. However the survival rate among the
      females over the studied period was higher than that among the males.

PMID- 23156063
TI  - [Biologic markers for early diagnosis of effects caused by exposure to coal dust
      in miners].
AB  - The authors studied changes in several laboratory values of coal miners in
      Russian Federation, defined information value of these changes and suggested
      complex of methods for early preclinical diagnosis of negative effects caused by
      coal dust in the miners. Dust-related respiratory diseases were proved to develop
      by stages on molecular level.

PMID- 23156064
TI  - [Practical experience of applying Order 302n released by Russian Federation
      Health and Social Development Ministry on April 12, 2011 "On approving the lists
      of hazardous and (or) dangerous occupational factors and works that require
      obligatory preliminary and periodic medical examinations (workup) and on regimen
      of obligatory preliminary and periodic medical examinations (workup) for workers
      exposed to intense labor and to hazardous and (or) dangerous work conditions"].
AB  - The analysis covered practical activities of medical department of Open-end Joint
      Stock Company, connected with the Order 302n released by Russian Federation
      Health and Social Development Ministry on April 12, 2011 "On approving the lists
      of hazardous and (or) dangerous occupational factors and works...". Findings are
      drawbacks in organization and carrying out the medical examinations mentioned in
      the Order. Financial and economic content of the medical examinations is
      evaluated. Some social consequences of the document are presented, and measures
      to optimize and adjust the Order to its practical application are suggested.

PMID- 23156065
TI  - Component-resolved diagnosis-assisted prescription of allergen-specific
      immunotherapy: a practical guide.
AB  - Allergen specific immunotherapy remains the only means to change the natural
      history of allergic disease. Thanks to the recent advances in molecular biology a
      large spectrum of purified allergen molecules are presently routinely available
      for diagnostic purposes. This review represents a practical guide on how to use
      these new diagnostic tools in order to detect precisely the primary sensitizing
      allergen sources in subjects showing a multiple sensitization to seasonal and/or
      perennial airborne allergens, thus avoiding the diagnostic mistakes that have
      been probably associated with the prescription and administration of several
      ineffective immunotherapies up to a recent past.

PMID- 23156066
TI  - Serum eotaxin levels in patients with chronic spontaneous urticaria.
AB  - Eotaxin is a potent agonist for CC chemokine receptor 3 that can attract
      eosinophils at sites of inflammation. Given the potential role of eosinophils in
      chronic spontaneous urticaria (CU), we measured serum eotaxin levels together
      with C-reactive protein in 100 CU patients who were characterized according to
      autologous serum skin test (ASST) and disease severity. Serum eotaxin
      concentration was significantly higher in CU patients (median 140.1 pg/ml, range
      33.7-718.7 pg/ml) than in 45 healthy controls (median 108.9 pg/ml, range 45.5
      409.4 pg/ml) (p = 0.032) Serum eotaxin concentration was not significantly
      different in ASST-positive and ASST-negative patients as well as in patients with
      different urticaria activity scores. However, eotaxin levels tended to be higher
      in patients with intense symptoms. In the 7 patients observed during CU
      exacerbation and during remission, eotaxin serum levels tended to decrease during
      remission, although statistical significance was not reached (median
      concentration decreased from 170.0 pg/ml to 123.8 pg/ml). CRP levels were not
      significantly different in CU patients and healthy subjects, although there was a
      trend towards higher levels in the former population. Furthermore, in the 7
      patients observed during CU exacerbation and during remission, CRP levels
      decreased significantly during remission (median concentration dropped from 4.1
      microg/ml to 0.7 microg/ml, p = 0.015). No significant correlation was found
      between eotaxin and CRP serum levels. These findings indicate that serum eotaxin
      levels are increased in CU patients, although they do not reflect strictly
      disease activity. A role for eotaxin in eosinophil attraction and activation in
      CU can be envisaged.

PMID- 23156068
TI  - Sensitization to rodents (mouse/rat) in an urban atopic population without
      occupational exposure living in Naples, Italy.
AB  - BACKGROUND: Until now no data on allergic sensitization to rodents allergens in
      Western Europe and Italy are available. The aim of this report was to investigate
      clinical significance and characteristics of IgE-mediated sensitization to
      mouse/rat (M/Rt) allergens in atopic subjects not occupationally exposed to these
      animals and living in urban area of Naples. METHODS: In 1765 consecutive
      outpatients, we selected all subjects with an immediate skin reaction to M/WRt
      dander clinical history including a carefijul evaluation ofthe modality of
      exposure, the results of skin-prick tests (SPTs) and specific IgE antibodies were
      recorded. RESULTS: Among 1185 SPT-positive patients, 22 were sensitized to M/Rt
      dander (respectively 1.60% and 0.59%). No patient was mono-sensitized Only three
      of 22 patients reported indoor conditions suggesting presence of rodents
      allergens at home. All patients exhibited low degree of SPT positivity and low
      levels of circulating IgE antibodies to M/WRt. Highfrequency of concomitant
      allergic sensitization to pet (and other animal) dander has been found.
      CONCLUSIONS: Our results suggest that role of allergic sensitization to rodents
      is negligible in atopic subjects without occupational exposure living in urban
      area of Naples. However, highly atopic individuals especially those already
      sensitized to common pet dander should be tested by SPTs/evaluation of serum
      specific IgE to rodents in the case they could begin an occupational exposure to
      M/Rt or keeping these animals as pets.

PMID- 23156067
TI  - Knowledge and health care resource allocation: CME/CPD course guidelines-based
      efficacy.
AB  - BACKGROUND: Most health care systems consider continuing medical education a
      potential tool to improve quality of care and reduce disease management costs.
      Its efficacy in general practitioners needs to be further explored. OBJECTIVE:
      This study assesses the effectiveness of a one-year continuing medical
      education/continuing professional development course for general practitioners,
      regarding the improvement in knowledge of ARIA and GINA guidelines and compliance
      with them in asthma management. METHODS: Sixty general practitioners, covering
      68,146 inhabitants, were randomly allocated to continuing medical
      education/continuing professional development (five residential events +four
      short distance-learning refresher courses over one year) or no training.
      Participants completed a questionnaire after each continuing medical education
      event; key questions were repeated at least twice. The Local Health Unit
      prescription database was used to verify prescription habits (diagnostic
      investigations and pharmacological therapy) and hospitalizations over one year
      before and after training. RESULTS: Fourteen general practitioners (46.7%)
      reached the cut-off of 50% attendance of the training courses. Knowledge improved
      significantly after training (p < 0.001, correct answers to key questions +13%).
      Training resulted in pharmaceutical cost containment (trained general
      practitioners +0.5% vs. controls +18.8%) and greater attention to diagnosis and
      monitoring (increase in spirometry +63.4%, p < 0.01). CONCLUSION: This study
      revealed an encouraging impact of educational events on improvement in general
      practitioner knowledge of guidelines and daily practice behavioral changes. Long
      term studies of large populations are required to assess the effectiveness of
      education on the behavior of physicians in asthma management, and to establish
      the best format for educational events.

PMID- 23156069
TI  - A case of allergy to zucchini.
AB  - A case of mono-sensitization to a heat- and pepsin-stable allergen in zucchini is
      described.

PMID- 23156070
TI  - A case of rice allergy in a patient with baker's asthma.
AB  - A case of rice allergy in a patient with bakers asthma is described. On ISAC 112
      IgE reactivity to wheat alpha-amylase/trypsin inhibitor (nTri a aA_TI) and lipid
      tranfer protein (rTri a 14) was found. We hypothesize that the reaction by oral
      ingestion was elicited by homologous molecules in rice seeds.

PMID- 23156071
TI  - Biosimilars might not measure up to health plan expectations.

PMID- 23156072
TI  - Is bundled payment an idea whose time has come?

PMID- 23156073
TI  - Cloud computing puts stakeholders on same page.

PMID- 23156074
TI  - What the Medicaid expansion under the ACA means for all MCOs.

PMID- 23156075
TI  - Three principles for improving health care delivery.

PMID- 23156076
TI  - Health care resource utilization and costs associated with restless legs syndrome
      among managed care enrollees treated with dopamine agonists.
AB  - PURPOSE: This study assessed the direct economic burden of restless legs syndrome
      (RLS) among patients treated with dopamine agonists (DAs) using a large United
      States managed care database. DESIGN: Retrospective database analysis.
      METHODOLOGY: Patients were required to have > or =1 prescriptions for a DA (i.e.,
      pergolide, pramipexole, ropinirole) between 1/1/2005 and 12/31/2007 (date of
      first DA, or "index"); continuous enrollment for > or =6 months before and > or
      =12 months after index; > or =1 diagnosis of RLS, before and after index; and no
      diagnosis of Parkinson's disease. Study measures included annual all-cause and
      RLS-related costs by care setting (hospitalizations, emergency room, office,
      pharmacy, other, total) and treatment-pattern events (discontinuations, switches,
      adjunctive treatments, titrations). PRINCIPAL FINDINGS: A total of 7,796 patients
      met the inclusion criteria. About 70% of patients received ropinirole, and 30%
      received pramipexole at index. Approximately 91% had >1 RLS-related office
      visits, and patients filled an average of 6.5 RLS-related prescriptions (DAs,
      gabapentin, carbidopa/levodopa) during the 1-year follow-up period. Mean (SD) all
      cause health care costs were $11,485 ($21,362) per patient, mostly due to
      multiple medical conditions occurring with RLS. RLS-related costs were 6.7% of
      total all-cause costs (mean [SD] $774 [$1,504]), consisting of office visits
      (16%), pharmacy (63%), and other costs (20%). Approximately 58% had a treatment
      pattern event suggesting a dopamine-related side effect. Opioids were the most
      commonly used adjunctive therapy (13% of patients). CONCLUSION: We found
      relatively low costs associated with RLS treatment. These findings should
      encourage expanding the coverage of treatment to reduce the suffering and costs
      associated with RLS.

PMID- 23156077
TI  - Clinical bundling pays off in antisepsis campaign.

PMID- 23156078
TI  - Shear bond strength comparison of two different adhesive systems.

PMID- 23156079
TI  - [Similarity of cycloprolylglycine to piracetam in antihypoxic and neuroprotective
      effects].
AB  - The antihypoxic activity of the endogenous cyclic dipeptide cycloprolylglycine
      (CPG) has been studied on a model of normobaric hypoxia with hypercapnia and its
      neuroprotective activity has been studied on a model of human neuroblastoma SH
      SY5Y cell damage by 6-hydroxydopamine. It is established that CPG exhibits the
      antihypoxic activity at doses of 0.5 and 1.0 mg/kg (i.p.) on outbred and BALB/c
      mice, but not on C57B1/6 mice. The neuroprotective activity of CPG was detected
      in 10(-5) - 10(-8) M concentration range only when the treatment was carried out
      24h before toxin introduction. The obtained data confirm the hypothesis that
      piracetam is a mimetic of the endogenous CPG neuropeptide.

PMID- 23156080
TI  - [Effect of a new triazinoindole derivative on the functional state of CNS in
      animals under normoxia and hypoxia conditions].
AB  - The influence of the new triazinoindole derivative encoded VM-606 on the
      individual behavior of rats in the open-field and elevated-plus-maze tests has
      been studied under normal conditions and after exposure to hypoxia with
      hypercapnia. It is established that VM-606 at a dose of 50 mg/kg under normoxia
      conditions reduces emotional anxiety, orientation-investigation activity, and
      mobility factor, while under hypoxic conditions this drug reduces the severity of
      behavioral changes in test animals. The experiments on mice showed that the
      compound studied potentiates the hypnotic effect of hexenal. It is suggested that
      VM-606 exhibits psychosedative and stress-protector properties, which play a
      certain role in its antihypoxic effect.

PMID- 23156081
TI  - [Effect of new derivatives of natural nitrogen-containing compounds on the level
      and metabolism of biogenic amines in brain structures and the life span of rats].
AB  - Effects of the analogs of transmitter amino acids on the level of biogenic amines
      and their metabolism in various structures of brain and on the life span of rats
      have been studied.

PMID- 23156082
TI  - [Neuroprotective effects of a dipeptide mimetic on the GK-2 nerve growth factor
      in model of permanent common carotid artery occlusion in rats].
AB  - The behavioral and biochemical effects of a new dipeptide mimetic of the GK-2
      nerve growth factor (NGF) have been studied on a model of chronic cerebral
      ischemia induced by permanent common carotid artery occlusion in rats. It is
      established that subchronic intraperitoneal injections of GK-2 (0.5 mg/kg) 4 h
      after surgery, followed by seven more injections made every 24 h, fully prevent
      the death of operated animals and reduces the development of habitation deficit
      (open-field test) and decrease in exploratory activity (novel object examination)
      two weeks after surgery, as well as fully restores the viability of cerebral
      cortex cells and decreases the hyperexpression of HSP70 in cerebral cortex.

PMID- 23156083
TI  - [Effect of losartan on acute renal failure induced by severe ethylene glycol
      poisoning in rats].
AB  - The effect of an angiotensin receptor II antagonist (losartan) on the model acute
      renal failure (ARF) induced by severe ethylene glycol poisoning at 2/3 LD50 has
      been studied in rats. It is established that losartan administration (20 mg/kg
      for 72 h) produces a significant (4-fold) increase in the animal death rate,
      which is associated with ARF transition to a decompensation stage. Pronounced
      changes in the qualitative and quantitative composition of diurnal diuresis, more
      than 8-fold increase in the creatinine level, and 18-fold increase in the blood
      urea have been observed. Thus, the administration of losartan to ethylene glycol
      poisoned rats causes more pronounced degeneration of proximal tubule epithelium
      and destruction of glomeruli. It is concluded that the use of losartan for the
      treatment of ARF is inexpedient.

PMID- 23156085
TI  - [Using cytoflavin for prophylaxis and treatment of cognitive amnestic disorders
      in patients with heavy toxicohypoxic damage of brain].
AB  - Results of the therapy of patients with toxicohypoxic encephalopathy diagnosis
      upon heavy poisoning by psychotropic substances are presented. It is established
      that administration of the antihypoxant cytoflavin provides for a substantial
      decrease in the extent of metabolic disorders related to the development of heavy
      hypoxia. The use of cytoflavin significantly decreases the degree of
      encephalopathy and favors faster and better recovery of the mnestic and other
      cognitive functions in patients upon heavy toxicohypoxic brain damage caused by
      acute poisoning.

PMID- 23156084
TI  - [An experimental study of the anti-inflammatory action of noopept and its effect
      on the level of cytokines].
AB  - The anti-inflammatory effects of noopept (dipeptide analog of piracetam) upon a
      single intraperitoneal (i.p.) administration at doses of 1, 5, and 10 mg/kg in
      comparison to the reference drug diclofenac (10 mg/kg, i.p.) have been studied on
      a model of acute exudative inflammation induced by carrageenan in outbred rats
      and concanavalin A (Con A) in CBA mice. The level of cytokines was studied on the
      lipopolysaccharide (LPS) model (single administration, 100 mg/kg, i.p.) with 5
      day administration of noopept at a dose of 5 mg/kg (i.p., before endotoxin
      injection) in C57BL/6 mice. The administration of noopept led to a significant
      suppression of the inflammatory response to both carrageenan and Con A. The
      administration of Con A caused a 16-fold increase in the level of IL-6
      interleukin in the blood serum of mice as compared to control. Noopept (5 mg/kg)
      reduced the level of IL-6 by a factor of 1.8 in the inflammatory response to Con
      A. The administration of LPS led to pronounced increase in the levels ofpro
      inflammatory IL-6 and TNF-alpha in the blood serum of test mice as compared to
      intact animals. The course administration of noopept (5 mg/kg) significantly
      decreased the level of IL-6 and reduced by half the level of TNF-alpha.

PMID- 23156086
TI  - [An experimental study of the efficiency of cycloferon in the complex
      chemotherapy of generalized drug-resistant tuberculosis].
AB  - The results of an experimental study of the efficiency of cycloferon included in
      a complex chemotherapy of generalized drug-resistant mycobacterium tuberculosis
      (MBT) are presented. It is established that cycloferon (3.6 mg/kg) produces a
      significant therapeutic effect, which is manifested by an increase in the lung
      clearance from MBT, a decrease in the spread of specific inflammation in the
      lungs, and the disappearance of MBT-induced alterations. In addition, activation
      of the signs of tension in the local immunity of lung tissues is observed as
      manifested by changes in the cellular composition of granulomas and more frequent
      detection of large lymphocytic and macrophage infiltration. The administration of
      cycloferon significantly increases the absorptive and digestive activity of
      phagocytosis by peritoneal macrophages, which has been inhibited during the
      development of experimental MBT infection.

PMID- 23156087
TI  - [Antihypertensive and neuroprotective activity of quercetin and its derivatives].
AB  - Data available in the literature on the pharmacological activity of quercetin and
      its derivatives, which possess various biological properties including
      antihypertensive and neurotropic activity, are reviewed. The mechanisms of these
      effects and results of clinical trials are considered and prospects for the
      clinical use of quercetin and its derivatives are discussed.

PMID- 23156088
TI  - [Prospects for the use of plant polysaccharides in complex treatment of malignant
      tumors].
AB  - The pharmacological properties of plant polysaccharides are reviewed and original
      experimental data on the properties of water-soluble polysaccharides isolated
      from Acorus calamus L. are presented. The possibility of using plant (in
      particular, Acorus calamus) polysaccharides to increase the effectiveness of
      anticancer treatment of transferred tumors and to reduce the toxic effects of
      cytostatic treatment on the normal cells of blood, liver, and epithelium of thin
      intestine in experimental animals has been demonstrated.

PMID- 23156089
TI  - Nanotechnologies and regenerative medical approaches for space and terrestrial
      medicine.
AB  - One purpose of the International Space Station (ISS) is to explore powerful new
      areas of biomedical science in microgravity. Recent advances in nanotechnology
      applied to medicine--what we now refer to as nano-medicine--and regenerative
      medicine have enormous untapped potential for future space and terrestrial
      medical applications. Novel means for drug delivery and nanoscale screening tools
      will one day benefit astronauts venturing to Mars and places beyond, while the
      space laboratory will foster advances in nanotechnologies for diagnostic and
      therapeutic tools to help our patients here on Earth. Herein we review a series
      of nanotechnologies and selected regenerative medical approaches and highlight
      key areas of ongoing and future investigation that will benefit both space and
      terrestrial medicine. These studies target significant areas of human disease
      such as osteoporosis, diabetes, radiation injury, and many others.

PMID- 23156090
TI  - Differential response of the gastrocnemius and soleus muscles of rats to chronic
      hypobaric hypoxia.
AB  - BACKGROUND: The hypothesis of the present study is that the occurrence of
      oxidative stress with exposure to chronic hypobaric hypoxia will be different in
      the gastrocnemius and soleus muscles as these two muscles differ in their fiber
      types. METHODS: Male Sprague-Dawley rats were divided into seven groups (I, II,
      III, IV, V, VI, VII). Groups I-V were exposed to an altitude of 25,000 ft (7620
      m) for 0, 3, 7, 14, and 21 d, respectively. Group VI and VII were given curcumin
      orally and exposed to an altitude of 25,000 ft (7620 m) for 0 and 14 d,
      respectively. On completion of exposure, the soleus and gastrocnemius muscle were
      removed and used for various estimations. RESULTS: Maximum changes were observed
      in 14-d exposed gastrocnemius muscle (GM) as compared to soleus muscle (SM).
      Lipid peroxidation (nmol x g(-1) of muscle) was higher in GM than SM in 14-d
      exposed rats (43.05 +/- 2.96 vs. 27.4 +/- 2.35, respectively). Similarly
      significant increases were observed in free radicals and protein carbonyl on
      exposure to hypobaric hypoxia. We also observed depletion of the antioxidant,
      reduced glutathione, in the exposed rats as compared to the control group. A
      significant reduction of 26% was observed in total protein of the GM as compared
      to a reduction of 13% in the SM. Myofibrillar proteins were also significantly
      decreased in the exposed groups. DISCUSSION: Hypobaric hypoxia affects different
      hind limb muscles differentially and the response of each muscle varies as a
      function of time. Gastrocnemius muscle is more vulnerable to hypobaric hypoxia
      induced oxidative stress in comparison to soleus muscle.

PMID- 23156091
TI  - Changes in central corneal thickness, intraocular pressure, and
      oxidation/antioxidation parameters at high altitude.
AB  - BACKGROUND: The authors aimed at investigating ophthalmological changes at high
      altitude and correlating this with blood oxidation/antioxidation parameters.
      METHODS: There were 40 volunteers who participated in the study. Initial
      ophthalmological examinations were performed at 3543 ft (1080 m) and repeated on
      the following day after the participants climbed to an altitude of 9186 ft (2800
      m) on Mt. Erciyes, Turkey. Venous blood samples were taken at both altitudes to
      evaluate total oxidative system (TOS) and antioxidative system (TAS) levels.
      RESULTS: IOP-right eyes at 3543 ft (1080 m) was 13.23 +/- 0.43 mmHg and
      significantly increased to 14.45 +/- 0.56 mmHg at 9186 ft (2800 m). LOP-left eyes
      at 3543 ft (1080 m) was 13.50 +/- 0.44 mmHg and increased to 14.13 +/- 0.54 mmHg
      at 9186 ft (2800 m) (P = n.s.). Central corneal thickness (CCT) of the right eyes
      was 540.98 +/- 4.34 microm at 3543 ft (1080 m) and significantly increased to
      549.73 +/- 4.59 microm at 9186 ft (2800 m). CCT of the left eyes was 542.13 +/-
      29.01 microm at 3543 ft (1080 m) and significantly increased to 547.23 +/- 4.59
      microm at 9186 ft (2800 m). Spherical equivalent refraction of right or left eyes
      did not show any significant changes. TOS at 3543 ft (1080 m) was 5.33 +/- 0.76
      micromol H2O2 equiv/L and significantly increased to 7.55 +/- 0.82 micromol H2O2
      equiv/L at 9186 ft (2800 m). TAS at 3543 ft (1080 m) was 2.45 +/- 0.12 micromol
      H2O2 equiv/L and decreased to 2.22 +/- 0.08 micromol H2O2 equiv/L (P = n.s.) at
      9186 ft (2800 m). There was a positive correlation between TAS and LOP at 9186 ft
      (2800 m). CONCLUSION: Increased CCT can be related to stromal edema caused by
      hypoxia's effect on corneal endothelial function. Although TOS increased at high
      altitude, TAS did not show any parallel increase. Since this was nonacclimatized
      climbing, the antioxidant system could not have reached sufficient levels to
      counterbalance the observed oxidant stress.

PMID- 23156092
TI  - Ligustrazine and the contractile properties of soleus muscle in hindlimb-unloaded
      rats.
AB  - BACKGROUND: In this study we investigated the effects of different dosages of
      ligustrazine (tetramethylpyrazine, Tmp) on soleus function and
      sarco(endo)plasmatic reticulum Ca(2+)-ATPase (SERCA) activity in 14-d hindlimb
      unloaded (HU) rats. METHODS: Female Sprague-Dawley rats were randomly divided
      into 4 groups (8 rats in each group): synchronous control (CON); HU plus
      intragastric water instillation (HU-W); HU plus different dosages of instilled
      Tmp (high: 42.53 mg x kg(-1), HU-TmpH; low: 21.15 mg x kg(-1), HU-TmpL). Muscle
      contraction force was examined in the soleus muscle. SERCA activity was assayed
      according to the released inorganic phosphate content. RESULTS: As expected, in
      HU-W, soleus peak twitch tension (Pt), peak tetanic tension (P0), time to 50%
      peak tension (TP50), time to peak tension (TPT), time from peak tension to 50%
      relaxation (RT50), and SERCA activity decreased, all compared with CON. HU-TmpH
      Pt and P0 values were 179% and 90% above HU-W, and 187% and 124% above HU-W in HU
      TmpL, respectively. TP50 and TPT values were 148% and 80% slower than HU-W with
      HU-TmpH and 95% and 32% in the HU-TmpL group, respectively. RT50 was slower than
      HU-W by 21% in HU-TmpH; SERCA activity elevated by 56% with HU-TmpH and by 72%
      with HU-TmpL. CONCLUSIONS: Ligustrazine may alleviate the decrease of muscle
      contractile force and increase of shortening velocity in atrophied soleus,
      possibly by means of elevated sarcoplasmic reticulum Ca(2+)-ATPase activity.

PMID- 23156093
TI  - Electrocardiographic abnormalities in medically screened military aircrew.
AB  - BACKGROUND: The European Society of Cardiology (ESC) recently published its
      updated recommendations for electrocardiogram (ECG) interpretation in athletes.
      It distinguishes ECG changes related to physical training (group 1 abnormalities)
      from training-unrelated changes (group 2) which may represent underlying
      electrical and structural heart disorders implicated in exercise related sudden
      cardiac death. This study sought to prospectively apply the ESC screening
      criteria to a large cohort of screened military aircrew. METHODS: This was a
      prospective observational study. The 12-lead ECGs of 868 consecutively evaluated
      healthy aircrew were analyzed for the presence of ESC-defined group 1 and 2
      abnormalities. RESULTS: The average age was 39.6 (11.2) yr (95.4% male). Overall,
      402 (46.3%) of ECGs could be classified as entirely normal. However, 466 ECGs
      (53.7%) were abnormal. Group 1 abnormalities were identified in 400 (46.1%)
      persons with 66 (7.6%) persons classified as having group 2 abnormalities. The
      most commonly identified group 1 ECG changes were sinus bradycardia (32.5%),
      early repolarization (11.8%), and isolated voltage criteria of left ventricular
      hypertrophy (10.1%). The most commonly noted group 2 abnormalities were left-axis
      deviation/left anterior hemiblock (2.4%), T-wave inversion (1.6%), and ST-segment
      depression (1.3%). Prolongation of the QTC > 0.46 s was observed in 0.69% of
      ECGs. CONCLUSIONS: The vast majority of ECGs performed in military aircrew could
      be classified as representing likely normal physiological changes. Training
      unrelated ECG changes, suggestive of possible genuine cardiac pathology, were
      observed in only a minority of persons who should be considered for further
      investigation.

PMID- 23156094
TI  - Risk factors for musculoskeletal injuries for soldiers deployed to Afghanistan.
AB  - PURPOSE: This study determined injury incidence and examined the association
      between musculoskeletal injuries and potential intrinsic and extrinsic risk
      factors. METHODS: This retrospective cohort study involved a survey of 593
      volunteers from two battalions of a Stryker Brigade Combat Team upon completion
      of a 12-mo deployment to Afghanistan. The survey included questions on physical
      characteristics, work duties, equipment worn, fitness training, and injuries
      experienced during the deployment. RESULTS: Of the surveyed soldiers, 45%
      sustained an injury during the deployment. Total injuries resulted in 5049 d of
      limited duty, an average of 8.5 d per injury. The body regions with the largest
      numbers of injuries were the low back (17.4%), knee (12.7%), and shoulder
      (10.0%). The majority (65%) of injuries occurred while working. The most frequent
      activities soldiers reported as the cause of injury were lifting and carrying
      (9.8%), dismounted patrolling (9.6%), and physical training (8.0%). Older age,
      higher enlisted rank, female sex, months deployed, more time spent standing,
      longer strength training sessions, heaviest load worn, and heavier or more
      frequent lifting tasks were all associated with injury. DISCUSSION: Tasks
      requiring physical energy expenditure such as load carriage, lifting, or standing
      resulted in an increased risk of musculoskeletal injury in this study.
      Lifting/carrying, dismounted patrols, and physical training were associated with
      26% of musculoskeletal injuries. The weight of loads carried and lifting may be
      exceeding the work capacity of the soldiers, resulting in injury. These injuries
      in turn limit available work days for military units, reducing combat power.

PMID- 23156096
TI  - Clothing buoyancy and underwater horizontal swim distance after exiting a
      submersed vehicle simulator.
AB  - BACKGROUND: Winter road workers, who drive heavy vehicles over ice-covered
      waterways, are at risk for ice failure, vehicle submersion, and subsequent
      drowning in frigid water. Although some jurisdictions require these workers to
      wear flotation clothing, there are concerns that, following an underwater exit in
      fast-moving water, increased clothing buoyancy may reduce ability to swim against
      the current to safely return to the ice opening. METHODS: Using a simulator in a
      swimming pool (3.7 m deep, 28 degrees C), 11 volunteers (5 women) were submersed
      8 times each to test the effects from both an Upright and an Inverted position of
      a normal nonflotation winter jacket (Control), a flotation Jacket, a flotation
      Overall, and a personal inflatable vest which was inflated (Inflated Vest) on
      underwater horizontal swim distance. Subjects also rated exit difficulty and
      impedance, psychological stress, and thermal comfort. RESULTS: Compared to
      Control, Jacket, and Overall, the Inflated Vest generally increased exit
      difficulty, escape impedance, and psychological stress, while greatly decreasing
      the ability to swim horizontally underwater before reaching the surface (Control,
      6.1 m; Jacket, 5.0 m; Overall, 3.4 m; and Inflated Vest only 1.4 m). Swim
      distance with the Overall was also significantly shorter than Control, but not
      Jacket. DISCUSSION: Flotation clothing (either Jackets or Overalls) is
      recommended for vehicle travel on ice because they do not impede underwater exit
      from a vehicle and allow significant horizontal underwater swim distance. An
      inflatable vest is not recommended because inappropriate premature inflation
      could increase exit impedance and decreased underwater swim distance.

PMID- 23156095
TI  - Forehead-mounted reflectance oximetry for in-cockpit hypoxia early detection and
      warning.
AB  - INTRODUCTION: Effective hypoxia-related mishap prevention relies upon aircrew
      rapid recognition of hypoxia symptoms. The objectives of this experiment were
      twofold: to compare the effectiveness of a forehead-mounted reflectance oximeter
      and finger-mounted pulse oximeter for application in a hypoxia early warning
      detection system, and to determine whether the forehead-mounted sensor could be
      placed within an aviation helmet. METHODS: Subjects donned an aviation flight
      mask and were instrumented with a forehead reflectance oximeter, a finger pulse
      oximeter, a blood pressure cuff, and a skin temperature sensor. Following
      instrumentation, subjects breathed ambient air for 10 min through the Reduced
      Oxygen Breathing Device (ROBD) to allow for acclimation. The baseline period was
      followed by one of two counterbalanced ascent profiles used to model rapid
      exposures to altitude. Data were collected at 1 Hz from both sensors for the
      duration of the protocol. RESULTS: Analyses indicated an exceptionally strong
      agreement between the forehead and finger sensors at all ranges of desaturation.
      The sensitivity data revealed that the forehead sensor was significantly faster
      when responding to rapid changes in SpO2 than the finger. The sensor was
      successfully integrated inside the helmet; however, once donned by the subject,
      there was considerable artifact due to pressure fluctuations. DISCUSSION: While
      these data may seem to suggest that the forehead sensor is accurate and sensitive
      to altitude induced changes in SpO2, major drawbacks exist for the technology
      utilized in the current study. Significant improvements aimed at diminishing
      noise, curbing motion artifact, and improving reliability are required to reduce
      errant measurements.

PMID- 23156097
TI  - Acute neurological symptoms during hypobaric exposure: consider cerebral air
      embolism.
AB  - Cerebral arterial gas embolism (CAGE) is well known as a complication of invasive
      medical procedures and as a risk in diving and submarine escape. In the
      underwater environment, CAGE is caused by trapped air, which expands and leads to
      lung vessel rupture when ambient pressure decreases during ascent. Pressure
      decrease also occurs during hypobaric activities such as flying and, therefore,
      CAGE may theoretically be a risk in hypobaric exposure. We reviewed the available
      literature on this subject. Identified were 12 cases of CAGE due to hypobaric
      exposure. Based on these cases, we discuss pathophysiology, diagnosis, and
      treatment of CAGE due to hypobaric exposure. The low and slow pressure decrease
      during most hypobaric activities (as opposed to diving) account for the low
      incidence of CAGE during these exposures and suggest that severe air trapping
      must be present to cause barotrauma. This is also suggested by the large
      prevalence of air filled cysts in the case reports reviewed. We recommend
      considering CAGE in all patients presenting with acute central neurological
      injury during or shortly after pressure decrease such as flying. A CT scan of
      head and chest should be performed in these patients. Treatment with hyperbaric
      oxygen therapy should be initiated as soon as possible in cases of proven or
      probable CAGE.

PMID- 23156098
TI  - +Gz-induced spinal symptoms in fighter pilots: operational and individual
      associated factors.
AB  - INTRODUCTION: Neck pain in fighter pilots has been studied by several air forces
      and found to be relatively common. The aim of this project was to study the
      incidence, characteristics, possible associated causative factors, and
      operational impact of neck pain in Royal Norwegian Air Force (RNoAF) fighter
      pilots. METHODS: The study was designed as a retrospective anonymous
      questionnaire survey, collecting data on age, aircraft type, flying hours, and
      physical activity. Any experience of spinal symptoms related to flying was
      included, as well as detailed questions on operational factors. Estimates
      regarding how neck symptoms influenced flying performance were established using
      visual analogue scales (VAS). Pilots also described their own in-flight
      techniques to avoid neck symptoms. RESULTS: Of respondents, 72% had experienced
      neck pain in relation to flying, while 35% had experienced back pain. Of these
      episodes, 93% were related to neck rotation. Mean G level for acute incidents of
      in-flight pain was 6.7 G. Total training time is on average higher in pilots who
      have no neck pain compared to those who have had neck pain events in the last 12
      mo; the mean training time being 3.9 h in the "no pain-group" vs. 2.7 h in the
      "pain group". "Checking six" was the most affected in-flight function.
      DISCUSSION: New technologies such as night-vision goggles and helmet-mounted
      displays increase helmet weight, thereby adding a higher strain to the neck even
      in moderate G environments. More research on specific prevention strategies is
      warranted in order to improve the in-flight working environment of fighter
      pilots.

PMID- 23156099
TI  - Superior vestibular dysfunction in severe decompression sickness suggests an
      embolic mechanism.
AB  - BACKGROUND: Both nitrogen bubble embolism and the difficulty of inner ear tissues
      to wash out nitrogen have been discussed as possible reasons for the selective
      vulnerability of the inner ear to decompression illness. This case report
      suggests that nitrogen bubble embolism plays a crucial role in the pathogenesis
      of inner ear lesions in decompression accidents. CASE REPORT: The current
      patient, a 48-yr-old male dive master, suffered a severe decompression illness
      with vertigo as the only residual symptom. At the 1-mo follow-up, neuro
      otological evaluation revealed a selective lesion of the superior vestibular
      division of the left labyrinth with normal functioning inferior vestibular
      division. At vestibular testing, there was no caloric response from the affected
      left ear, and the head impulse tests for the lateral and anterior semicircular
      canal were also impaired. Tests of vestibular evoked myogenic potentials (VEMP)
      showed divergent results. Ocular VEMP in response to left ear stimulation were
      absent, whereas the cervical VEMP were completely symmetrical and normal. Thus,
      the lesion profile implies a partial vestibular loss selectively affecting the
      superior vestibular division of the inner ear. DISCUSSION: The most likely
      explanation for such a selective injury seems to be bubble microembolism coupled
      with both the specific anatomy of this terminally supplied subunit, and with the
      slow nitrogen wash-out of the vestibular organ.

PMID- 23156100
TI  - Airborne visibility indicator system.

PMID- 23156101
TI  - You're the flight surgeon: sudden onset of flying phobia.

PMID- 23156102
TI  - You're the flight surgeon: ocular hypertension.

PMID- 23156103
TI  - This month in aerospace medicine history.

PMID- 23156104
TI  - Meningitis mess. The trouble with custom-made drugs.

PMID- 23156105
TI  - [Formation of therapeutic group of casualties in local wars and armed conflicts].
AB  - The necessity of improvement of the therapeutic care organization in the RF Armed
      Forces is dictated by the existing military threats. Conflicts between states or
      within a single country along with inefficiency of diplomatic, social and
      political efforts may lead to armed conflicts or local wars. Analysis of medical
      support results shows the consistent prevalence of therapeutic group of
      casualties in the overall structure of medical losses. 35-50% of all sanitary
      losses is accounted for by somatic diseases. Moreover, their structure is similar
      to the structure of the army's peacetime morbidity rate. Respiratory diseases
      head the list of somatic diseases in military personnel. Next--diseases of the
      digestive and circulatory systems. One of the most important tasks for physicians
      in wartime is early diagnosis and treatment of visceral pathology in the wounded.
      An additional point is that the use of tactical nuclear weapons during the armed
      conflict or local war cannot be completely excluded. There is also a real risk of
      nuclear and chemical facilities damage, with consequences that are comparable to
      the use of nuclear or chemical weapons. Thus, in the course of armed conflict or
      local war, military physicians can meet all possible therapeutic spectrum of
      pathology: from visceral pathology of peace and wartime to combat related
      therapeutic pathology.

PMID- 23156106
TI  - [Organizational and methodological approaches to the medical rehabilitation of
      the wounded from the consequences of combat trauma in the upper limb in
      rehabilitation center].
AB  - This article discusses the possibility of optimizing the organizational and
      methodological approaches to the medical rehabilitation of the wounded from the
      consequences of combat trauma of the upper extremities in rehabilitation center.
      Clearly the implementation of organizational measures and technologies optimized
      medical rehabilitation, restoration of function provided the injured extremity:
      total of 152 (64%) injuries, partial in 26 (11%) injuries, as well as the
      stability of long-term results. Optimization using the traditional methods of
      treatment (biomehanoterapiya, chiropractic, massage, acupuncture, integrated
      technology) has increased the effectiveness of medical rehabilitation at 35%.

PMID- 23156107
TI  - [Analysis of the health of citizens of military age in Orenburg region].
AB  - Results of medical examination of citizens of military age living in the Orenburg
      region for a decade are given. Noted that over the study period in the region
      have been positive changes: performance fitness for military service on health
      increased from 62.9% in 2000 to 67.7% in 2009 and projected to the positive
      dynamics in 2020 also marked improvement in physical fitness and the citizens of
      military age, a significant reduction in the number of recruits with poor and low
      power.

PMID- 23156108
TI  - [Directions of interdepartmental interaction in case of delivery of health care
      for injured in emergency situations in stationing sites of navy].
AB  - In points basing of navy will remain probability of emergence of emergency
      situations which is connected with existence of the enterprises of the industry
      and objects of navy. As a result of emergency situations in places of basing of
      navy discrepancy of prospective sanitary losses to possibilities of forces and
      means of a health service of fleet that demands interaction with health services
      of other ministries and departments is probable. Criterion of need of interaction
      is the ratio of quantity struck and possibilities of a health service of navy.
      Plans of interaction of a health service of fleet with medical institutions of
      other departments should provide options of use of available forces and means of
      medical institutions in garrisons for joint assistance struck in an emergency
      situation. The questions solved during interaction should become: radiation,
      chemical, biological survey; allocation of forces and means for rendering of
      medical care; use of sanitary transport; organization of sanitary processing,
      etc.

PMID- 23156109
TI  - [Analysis of frequency and structure of cerebrovascular diseases in servicemen
      during the military physician expertise].
AB  - Analysis of the results of medical inspection of soldiers under contract taken
      place in 2005-2009 is given. In 48.9% of cases was revealed diseases of blood
      circulatory system. In patients with cardiovascular events in 42.2% of cases
      different forms of cerebrovascular diseases were diagnosed. It shows high level
      of these diseases and its early progression among the servicemen. According to
      the authors, specific peculiarities of intensive military service provide the
      early progression of diseases. In such a case, presence of cerebrovascular
      diseases influences on expert decisions about professional suitability of
      servicemen for some military specialties including the level of suitability for
      military service.

PMID- 23156110
TI  - [About the causes of inveterate cystitis in young women].
AB  - 16 female patients,aged 28.6 +/- 3.2 years, with recrudescent inveterate cystitis
      were examined for the purpose of improvement of treatment of chronic cystitis.
      The examined patients noted relapse of disease after sex intercourse. Spectrum of
      diagnosed uropathogens in female patients corresponds to the structure of
      bacterio from urina taken after prostate milking and prostatic fluid of patients'
      intercourse partners. The given uropathogens also corresponds to the structure of
      contagium of urinary tract in young men. Connection between urogenital biotope
      and biotope of prostate as a vessel of persistence infection is related.
      Recrudescent inveterate cystitis in young women may be result from latent
      inveterate bacteritic prostatitis in their intercourse partners. Effectiveness of
      treatment and prophylaxis of recrudescence of inveterate cystitis in young women
      depends on timely diagnostics, treatment, and prophylaxis of inveterate
      bacteritic prostatitis in their intercourse partners.

PMID- 23156111
TI  - [Diagnostics and treatment of patients with sarcoidosis in multidisciplinary
      military hospital].
AB  - The authors analyzed the methods of diagnostics, clinical peculiarities of
      sarcoidosis in different groups of patients, treated in multidisciplinary
      military hospital. The authors also analyzed the possibility of estimation of
      optimum diagnostic and medical tactics on the basis of prospective observation
      after patients with morphologically confirmed sarcoidosis, treated in pulmonary
      department of the Main Military Clinical Hospital n. a. N.N. Burdenko.

PMID- 23156112
TI  - [Peculiarities of adaptation of servicemen service].
AB  - Review of issues about the adaptation of servicemen in the process of military
      service is presented. Characteristics of military service, conditions and levels
      of official-military activity, peculiarities of adaptation, factors providing
      progression of psychosomatic diseases and dysaptation, concept "occupational
      health" are considered.

PMID- 23156113
TI  - [Analysis of infringements of exchange processes in combatatnts with
      psychosomatic disorders in the period after participation in operations].
AB  - Analysis of clinical and biochemistry blood test parameters was conducted. It was
      revealed that metabolic disorders with predomination of catabolic reactions are
      typical for combatatnts who took part in military actions. So, the blood serum
      glucose value in the patients group is higher than in the control group. Military
      men with psychosomatic disorders are characterized by the decrease of cholesterol
      and triglycerides. The obtained data is supported by the results of model
      analysis of posttraumatic stress disorders in animals.

PMID- 23156114
TI  - [Visual illusions and moving horizon].
AB  - Results of psychological "additional investigation" of the crash of Boeing-737,
      "Aeroflot-Nord" on 14.09.2008 near Perm are presented. 37 pilots from the one of
      the leading airline companies sensed the attitude and rolling out the aircraft to
      the forward flight under the moving horizon with straight display of bank and
      tangage (view from the aircraft to the ground) in model conditions. 29 pilots
      (78.4%) made a mistake at determining the roll direction and tangage, they made a
      mistake at determining the roll direction 61 times (16.4%) and 44 times at
      determining the tangage direction, in other words they confused left and right
      bank and also nose-up and nose-down. Visual illusions of mobility of space and
      handling of ground (instead of aircraft) during the flight were revealed in
      pilots. These illusions may be the important cause of the following crashes. The
      necessity of "back" faultless display of bank in all aircrafts of civil aviation
      and development of computer complex for training of visual spatial orientation is
      proved.

PMID- 23156115
TI  - [About the fitness to work of sailors during the campaign of surface vessel in
      conditions of Polar Region].
AB  - The authors analyzed functional condition of organism and peculiarities of
      fitness to work of sailors with the help of physical load during the campaign of
      surface vessel of special assignment in conditions of Polar region with
      complicated complex of unfavourable factors of environment. Index of physical
      efficiency and regulation of heart rhythm of the personnel in dynamic of 2-month
      campaign are analyzed. Connection between this data and regular sanitary
      exercises is explored. Influence of physical load as an independent training and
      in special program is estimated. The authors thought that the criterion of
      optimality is preservation of initial level of efficiency during the campaign. It
      is proved that wrong-running independent training may cause worsening functional
      condition of the organism.

PMID- 23156116
TI  - [Medical supply of the Russian army during the Patriotic War in 1812].
AB  - The article is devoted to the 200th anniversary of the victory of the russian
      weapon in the Patriotic War in 1812. Russian military medics lended a weighty
      contribution to destruction of the strongest Napoleonic army. Together with
      russian soldiers they suffered woes and hardships, accompanied Russian soldiers
      not only in moments of victories but also in the most hard moment, saving lives
      of wounded and illed, soldiers and civil population. Structure of medical service
      of the Russian Army, types of delivery of health care, some epispdes of the work
      of military medics are described.

PMID- 23156117
TI  - [Act of bravy of Surgeon in ordinary to the King Yustus Loder].
AB  - Yustus Christian (in russian transcription Christian Ivanovich) Loder (1753-1832)
      studied in Gottingen University, where in 1777 defended degree of Doctor of
      Medicine and Surgery. The article is devoted to his activity in organisation of
      delivety of the health care to the wounded during the Patriotic War in 1812 year.
      From September 1812 to May 1813 30 126 patients were treated in the hospitals
      controlled by Loder, 23 413 stepped back into the ranks, in other words almost
      77%. 2096 patients died (7%). Loder was against so called early amputation widely
      propogated by surgeon-in-chief of French army D.Zh.Larrey as the only life
      preserver.

PMID- 23156118
TI  - [Hospital schools during the Russian-Turkish War 1735-1739].
AB  - In 1733 besides the school before the Moscow hospital also three hospital schools
      were open before Saint-Petersburg terrestrial and admiralty hospitals and before
      the hospital in Kronshtadt. The process of transfer of students from schools to
      army was the most intensive during the military conflicts with that is rich
      Russian history in XVIII century. According to documents, presented in the
      article, during the Russian-Turkish War in 1735-1739 hospital schools worked
      active and discharged a task of recruiting of medical service of the Russian
      Army. The most important precondition was basis of military-medical education
      grounded by Peter at the beginning of XVIII century.

PMID- 23156119
TI  - Effect of wheat flour fortified with sodium iron EDTA on urinary zinc excretion
      in school-aged children.
AB  - BACKGROUND: Foods fortified with sodium iron ethylenediaminetetraacetate
      (NaFeEDTA) have been shown to improve iron status in children, but little is
      known about the effect of this salt on urinary zinc excretion, particularly in
      children. This is particularly relevant, since zinc deficiency is known to limit
      growth and development in young children. OBJECTIVE: To determine the effect of
      NaFeEDTA-fortified wheat flour on urinary zinc excretion. METHODS: This study was
      a part of a randomized, controlled trial that was carried out among 6- to 13-year
      old iron-depleted schoolchildren (n = 179) who had received either a NaFeEDTA
      fortified wheat meal (iron group) or an identical control meal without added iron
      (control group) for a period of 7 months. Urinary zinc concentration was assessed
      at the end of the intervention period by spot urine samples. RESULTS: Iron status
      in the iron group was significantly improved according to measurements of
      hemoglobin and serum ferritin (p < .001). However, there was no significant
      difference in urinary zinc excretion between the iron group (median, 38.4
      microg/dL; 25th-75th percentiles, 18.2-67.1 microg/dL) and the control group
      (median, 33.1 microg/dL; 25th-75th percentiles, 12.4-54.2 microg/dL).
      CONCLUSIONS: Iron fortification of foods with NaFeEDTA does not affect urinary
      zinc excretion in children.

PMID- 23156120
TI  - Iron-fortified wheat flour and iron deficiency among women.
AB  - BACKGROUND: Iron deficiency is estimated to impact more than 1.6 billion
      individuals worldwide, affecting child, maternal, and perinatal mortality. Iron
      supplementation, fortification, and dietary diversification are strategies to
      reduce the prevalence of iron deficiency. However, there are relatively few
      studies demonstrating the effectiveness of iron-fortified wheat flour as an
      intervention. OBJECTIVE: To assess the relationship between average monthly per
      capita household consumption of iron-fortified wheat flour and iron deficiency
      among women of childbearing age in Oman. METHODS: Data were obtained from the
      National Micronutrient Status and Fortified Food Coverage Survey, 2004. Iron
      deficiency status was compared between women living in households with a monthly
      per capita consumption of iron-fortified wheat flour of 1 kg or more and women
      living in households with a monthly per capita consumption of iron-fortified
      wheat flour of less than 1 kg. The analyses excluded women with elevated or
      unknown levels of C-reactive protein and controlled for characteristics of the
      women and household demographics. RESULTS: Consumption of iron-fortified wheat
      flour was associated with a lower prevalence of iron deficiency among women in
      our sample (adjusted odds ratio, 0.60), after controlling for age, employment
      status, marital status, intake of iron or multivitamin supplements, self-reported
      presence of a blood disorder, household income, educational level of head of
      household, and family size. CONCLUSIONS: These results suggest that women in our
      study living in households with a greater consumption of iron-fortified wheat
      flour have a lower prevalence of iron deficiency; however, additional study is
      needed.

PMID- 23156121
TI  - Vegetable oil of poor quality is limiting the success of fortification with
      vitamin A in Egypt.
AB  - BACKGROUND: Fortification of vegetable oil with vitamin A is considered a cost
      effective and simple to implement strategy, but the stability of vitamin A
      remains a limiting factor. To account for losses of vitamin A, oil producers add
      an overage. Optimizing the amount of this overage can result in considerable
      savings for industry and government while ensuring a supply of adequately
      fortified oil to consumers. OBJECTIVES: To estimate vitamin A losses in oil with
      different chemical characteristics. METHODS: Samples of fortified oils with
      different chemical characteristics were collected from two Egyptian companies
      (oil A and B) and stored for 1 month. Vitamin A levels were analyzed periodically
      during storage to determine losses over time, and peroxide values were
      determined. RESULTS: Fortified oil B, with a high peroxide value (5.8 mEq/kg),
      exposed to sunlight had significantly higher losses of vitamin A after 4 weeks
      than fortified oil A, with a low peroxide value (0.4 mEq/kg): 31.1% vs. 19.7% (p
      < .001), respectively. In semidark conditions, the vitamin A losses after 4 weeks
      in fortified oil B and fortified oil A were significantly different: 26.1% and
      0.7% (p < .001), respectively. In an accelerated storage test, the vitamin A loss
      in 8 days was 48.3% for fortified oil B and 4.2% for fortified oil A (p < .001).
      CONCLUSIONS: This study shows a significant effect of peroxide level (one
      indicator of the quality of oil) on the stability of vitamin A, regardless of
      storage conditions. To optimize and sustain vitamin A levels in fortified oil,
      governments and industries should minimize the peroxide level to less than 2
      mEq/kg at production.

PMID- 23156122
TI  - Effects of third trimester counseling on pregnancy weight gain, birthweight, and
      breastfeeding among urban poor women in Bangladesh.
AB  - BACKGROUND: Maternal malnutrition and poor gestational weight gain are the most
      important causes of low birth weight and high rates of newborn mortality.
      OBJECTIVE: To assess the effects of nutrition counseling in the third trimester
      of pregnancy on maternal weight gain, birth weight of newborn, and breastfeeding
      practices. METHODS: This was a longitudinal experimental study with nutrition
      intervention for a period of 3 months. One hundred fifteen women (57 in the
      intervention group and 58 in the comparison group) who were visiting the Maternal
      and Child Health Training Institute at 6 months of pregnancy were randomly
      selected. The intervention group was given nutrition education twice in the first
      month and once a month for the next 2 months before delivery; the comparison
      group received routine hospital advice on food intake, immunization, personal
      hygiene, and breastfeeding. The women were weighed monthly up to delivery, the
      newborn infants' birth weights were measured within 24 hours after delivery, and
      breastfeeding practices were observed 1 month after delivery. RESULTS: Women in
      the intervention group gained 1.73 kg more weight during the third trimester than
      women in the comparison group (5.61 vs. 3.88 kg, p < 0.001). The mean birthweight
      of babies of women in the intervention group was 0.44 kg greater than that of
      babies of women in the comparison group (2.86 vs. 2.42 kg, p < 0.001). In the
      intervention group, 10.5% of babies were born with low birthweight, compared with
      48.3% of the babies of women in the comparison group (p < 0.001). In the
      intervention group, 75.4% of mothers initiated breastfeeding within 1 hour after
      birth, compared with 34.5% of mothers in the comparison group (p < 0.001).
      CONCLUSIONS: Nutrition education only during the third trimester improved weight
      gain during pregnancy, reduced 78% of low birth weight, and improved
      breastfeeding practices.

PMID- 23156123
TI  - Performance of iron spot test with Arabic bread made from fortified white wheat
      flour.
AB  - BACKGROUND: The iron spot test (IST) is a simple qualitative technique for
      determining the presence of added iron in fortified flour. IST performance in
      bread has never been investigated. If found to perform well, the IST has the
      potential to provide a field-friendly method for testing bread and thus support
      the monitoring and evaluation of flour fortification programs. OBJECTIVE: To
      assess the performance of the IST in Arabic bread made from white wheat flour.
      METHODS: Bread samples were collected from 1,737 households during a national
      micronutrient survey in Jordan. A subsample of Arabic bread (n = 44) was
      systematically selected for testing by both the IST and spectrophotometry
      (criterion reference). Performance measures (sensitivity, specificity, and
      positive and negative predictive values) were calculated using five cutoffs to
      define the presence of added iron, including > or = 15.0 ppm (approximate level
      of natural iron in Arabic bread) and four additional cutoffs based on test
      performance. RESULTS: The iron contents of samples testing negative by IST ranged
      from 10.4 to 18.4 ppm, with one outlier at 41.0 ppm, which was excluded from
      subsequent analyses. The iron contents of samples testing positive by IST ranged
      from 16.1 to 38.4 ppm. With the exception of negative predictive values for the
      two lowest cutoffs (> or = 15.0 and > or = 16.1 ppm), all performance measures
      exceeded 83.3%. CONCLUSIONS: These results show promise for the IST as an
      inexpensive, field-friendly method for testing bread that could have a useful
      role in the monitoring and evaluation process for flour fortification programs.

PMID- 23156124
TI  - Cost analysis of community-based daily and weekly programs for treatment of
      moderate and mild wasting among children on Nias Island, Indonesia.
AB  - BACKGROUND: Ready-to-use food in the form of biscuits (RUF-Nias biscuit) was
      locally produced for rehabilitation of moderately and mildly wasted (weight-for
      height z-score > or = -3 to < -1.5 SD) children on Nias Island, Indonesia. Daily
      programs were performed in semiurban settings, and weekly programs took place in
      rural areas. OBJECTIVE: To analyze the cost of daily and weekly distribution and
      supervision of RUF-Nias biscuit programs. METHODS: The costs of the daily and
      weekly programs were derived from the financial report and interviews with
      program implementers and participating households. Costs were calculated on the
      basis of total rehabilitation costs per child per day required to achieve a
      target weight-for-height z-score > or = -1.5 SD in daily and weekly programs.
      RESULTS: Institutional costs to the implementing organization were similar for
      both programs (approximately US $4 per child per day). The daily programs
      resulted in a significantly higher proportion of recovered children (78.6% vs.
      65.4%) and higher weight gain (3.7 vs. 2.2 g/kg/day) than the weekly programs.
      About 6% to 7% of the total cost of the programs was accounted for by locally
      produced RUF-Nias biscuits. The social cost borne by the community for the weekly
      programs was about half that for the daily programs. CONCLUSIONS: The daily
      programs achieved better results for the implementing organization than the
      weekly programs; however, the weekly programs were preferred by the community
      because of the lower time constraints and the lower opportunity cost of time. The
      willingness of community and household members to invest their time in more
      intensive activities in the daily programs led to better program outcomes.

PMID- 23156125
TI  - Evaluation of iodine content in table salt consumed in Democratic Republic of
      Congo.
AB  - BACKGROUND: DR Congo has adopted universal salt iodization to reduce disorders
      due to iodine deficiency. Since 1994, only iodized salt can be imported, but
      there is currently no routine monitoring of the iodine content of distributed
      salt. It is therefore unclear if iodine deficiency remains a health problem,
      particularly in pregnant women. OBJECTIVE: To evaluate the iodine content of salt
      in households of pregnant women in Lubumbashi. METHODS: We conducted a survey of
      the iodine content of salt consumed by 375 women presenting at prenatal
      consultations in three socially different areas of Lubumbashi: urban, semiurban,
      and rural. The women were questioned about where they purchased salt, how it was
      packaged, and how they stored the salt, and each woman provided a sample of salt
      for determination of its iodine content by the iodometric method. RESULTS: Most
      women (84.3%) bought salt in the public markets, mainly in bulk (93.6%); 80.0%
      stored salt in plastic boxes. The median iodine content was 27.5 ppm (IQR, 16.0
      38.1) in urban areas, 19.0 ppm (IQR, 7.4-31.7) in semiurban areas, and 20.1 ppm
      (IQR, 5.3-31.7) in rural areas. The iodine content was less than 15 ppm (minimum
      threshold) in 36.3% of samples, including 13.9% without any detectable iodine.
      The iodine content was above 40 ppm (maximum limit) in 18.9% of samples. Only
      44.8% of salt samples had adequate iodine content. CONCLUSIONS: The population of
      Lubumbashi remain at risk for hypothyroidism and hyperthyroidism. A effective and
      regular system for the control of iodin content in distributed salt is needed in
      DR Congo.

PMID- 23156126
TI  - Stay ahead of the pack.

PMID- 23156127
TI  - Practice assessment: what's in it for me?

PMID- 23156128
TI  - Cloned notes: the time is ripe to review your practices. Office of the inspector
      general initiates E&M services review.

PMID- 23156129
TI  - Tackling population health management: it boils down to HIT. MGMA-ACMPE members
      get exclusive look at industry research.

PMID- 23156130
TI  - What drives physician salaries?

PMID- 23156131
TI  - Who's in the driver's seat? Physician compacts help you steer your practice.

PMID- 23156132
TI  - Seen the new hybrids. A blend of concierge and traditional practice models
      emerges.

PMID- 23156133
TI  - Schedule tests in advance for higher efficiency and happier patients.

PMID- 23156134
TI  - Social media: real life online.

PMID- 23156135
TI  - Fair-market value testing.

PMID- 23156136
TI  - Working together: keys for successful partnerships with specialists.

PMID- 23156137
TI  - Don't let your PDA go MIA.

PMID- 23156138
TI  - So many patients, one little form. Association member streamlines patient
      scheduling process.

PMID- 23156139
TI  - Reach for the stars: learning to see beyond the workday. Lawrence schindler, MHA,
      MGMA-aCMPE member, consultant, Apache Junction, Ariz.

PMID- 23156140
TI  - Mathematical modeling, spatial complexity, and critical decisions in tsetse
      control.
AB  - The tsetse fly complex (Glossina spp.) is widely recognized as a key contributor
      to the African continent's continuing struggle to emerge from deep economic,
      social, and political problems. Vector control, the backbone of intensive efforts
      to remove the human and livestock trypanosomosis problem, has been typified by
      spectacular successes and failures. There is widespread agreement that integrated
      vector control, combined with direct disease treatment and prevention, has to
      play a major role in alleviating the tsetse burden in Africa. Mathematical and
      computer-based simulation models have been extensively used to try to understand
      how best to manage these control efforts. Such models in ecology have been
      helpful in giving broad generalizations about population dynamics and control.
      Unfortunately, in many ways they have inadequately addressed key aspects of the
      fly's biology and ecology, particularly the spatio-temporal variability of its
      habitats. These too must factor in any control efforts. Mathematical models have
      inherent limitations that must be considered in their use for control programs.
      In this review, we consider some of the controversies being debated within the
      field of ecology and evolution about the use of mathematical models and
      critically review several models that have been influential in structuring tsetse
      control efforts. We also make recommendations on the appropriate role that
      mathematical and simulation models should play when used for these purposes.
      Management programs are often vulnerable to naively using these models
      inappropriately. The questions raised in this review will apply broadly to many
      conservation and area-wide pest control programs with an ecological component
      relying on mathematical and computer simulation models to inform their decisions.

PMID- 23156141
TI  - A new low-cost procedure for detecting nucleic acids in low-incidence samples: a
      case study of detecting spores of Paenibacillus larvae from bee debris.
AB  - American foulbrood, because of its virulence and worldwide spread, is currently
      one of the most dangerous diseases of honey bees. Quick diagnosis of this disease
      is therefore vitally important. For its successful eradication, however, all the
      hives in the region must be tested. This is time consuming and costly. Therefore,
      a fast and sensitive method of detecting American foulbrood is needed. Here we
      present a method that significantly reduces the number of tests needed by
      combining batches of samples from different hives. The results of this method
      were verified by testing each sample. A simulation study was used to compare the
      efficiency of the new method with testing all the samples and to develop a
      decision tool for determining when best to use the new method. The method is
      suitable for testing large numbers of samples (over 100) when the incidence of
      the disease is low (10% or less).

PMID- 23156142
TI  - Effects of soil-applied imidacloprid on Asian citrus psyllid (Hemiptera:
      Psyllidae) feeding behavior.
AB  - The Asian citrus psyllid, Diaphorina citri Kuwayama (Hemiptera: Psyllidae), is
      one of the most important pests of citrus (Citrus spp.) because of its status as
      a vector of Candidatus Liberibacter asiaticus (Las), the bacterium associated
      with citrus greening disease. The use of insecticides for vector control is the
      primary method of managing the spread of this pathogen. Imidacloprid is an
      insecticide commonly applied to the root zone of young citrus trees to provide
      systemic protection from pests. The effects of imidacloprid on feeding behavior
      of D. citri have not been studied in much detail. The purpose of this study was
      to examine the effects of imidacloprid application on feeding behavior of D.
      citri and to determine whether use of this systemic insecticide could have any
      effect on pathogen transmission by D. citri. A direct current electrical
      penetration graph monitor was used to record D. citri feeding behaviors for 12-h
      periods on mature and young leaves of imidacloprid-treated and -untreated citrus
      seedlings. Overall, compared with untreated plants, the feeding behavior of D.
      citri was disrupted on imidacloprid-treated plants via reduction in the number of
      probes, as well as durations of average probes, initial stylet contact with
      phloem, phloem salivation, and phloem ingestion. The results of this study
      demonstrate that soil applications of imidacloprid can reduce the probability of
      citrus plants becoming inoculated with Las through a reduction in the number and
      duration of phloem salivation events by D. citri. Furthermore, Las acquisition
      from infected citrus is greatly reduced as a result of decreased phloem ingestion
      by D. citri on imidacloprid-treated plants.

PMID- 23156143
TI  - Interspecific interaction between Spodoptera exigua multiple nucleopolyhedrovirus
      and Microplitis bicoloratus (Hymenoptera: Braconidae: Microgastrina) in
      Spodoptera exigua (Lepidoptera: Noctuidae) larvae.
AB  - Baculoviruses and parasitoids are important biological control factors of insects
      in integrated pest management. Microplitis bicoloratus Chen (Hymenoptera:
      Braconidae: Microgastrina) is a solitary endoparasitoid of beet armyworm,
      Spodoptera exigua (Hubner) (Lepidoptera: Noctuidae) larvae. M. bicoloratus
      parasitized first to third instars of S. exigua and most effectively parasitized
      second instars. The survival rate of parasitoids emerging from S. exigua multiple
      nucleopolyhedrovirus (SeMNPV)-infected hosts decreased with increasing SeMNPV
      doses at second to fourth instars. In addition, the mortality rate of the host
      was > 80% when coinfected with SeMNPV and M. bicoloratus, regardless of virus
      doses or the timing of virus treatment. Occlusion body production was
      significantly reduced in parasitized hosts. A comparison of host weights showed
      that hosts coinfected with SeMNPV and M bicoloratus were significantly lighter
      than those infected with SeMNPV alone, suggesting that the decrease in virus
      yield resulted from a reduction in larval growth. The viral genome copy number in
      parasitized host was significantly lower than that in nonparasitized host at 48
      and 72 h postinfection. These results suggest that SeMNPV and M. bicoloratus are
      compatible as S. exigua control agents.

PMID- 23156144
TI  - Identification and impact of natural enemies of Bactericera cockerelli
      (Hemiptera: Triozidae) in Southern California.
AB  - Bactericera cockerelli (Sulc) (Hemiptera: Triozidae) is a major pest of potato,
      (Solanum tuberosum L.), tomato (Solanum lycopersicum L.), and peppers (Capsicum
      spp.). The purpose of our research was to identify and determine the impact of
      natural enemies on B. cockerelli population dynamics. Through 2 yr of field
      studies (2009-2010) at four different sites and laboratory feeding tests, we
      identified minute pirate bug, Orius tristicolor (White) (Hemiptera:
      Anthocoridae); western bigeyed bug, Geocoris pallens Stal (Hemiptera:Geocoridae),
      and convergent lady beetle, Hippodamia convergens Guerin-Meneville (Coleoptera:
      Coccinellidae) as key natural enemies of B. cockerelli in southern California
      potatoes, tomatoes, and bell peppers. In natural enemy exclusion cage experiments
      in the potato crop and in American nightshade, Solanum americanum Miller, the
      number of B. cockerelli surviving was significantly greater in the closed cage
      treatments, thus confirming the affect natural enemies can have on B. cockerelli.
      We discuss how this information can be used in an integrated pest management
      program for B. cockerelli.

PMID- 23156145
TI  - Identification of Orius (Heteroptera: Anthocoridae) females based on egg
      operculum structure.
AB  - Naturally occurring predators of the genus Orius (Heteroptera: Anthocoridae)
      often suppress agricultural pests in insecticide-free environments. Knowledge of
      Orius species composition in the field is important because species vary in their
      biology, prey preference, and ability to suppress pest populations. However,
      field-collected Orius bugs are often female biased and the identification of
      Orius females may be unreliable and time consuming. Identification of Orius
      species based on egg structure may allow easy and nondestructive identification
      of females, by inspecting the eggs they deposit, and identification of species
      that reproduce in the field. The aim of the current study was to illustrate how
      several Mediterranean Orius species could be identified using egg opercula. For
      this purpose, the structure of the operculum was described for eggs deposited by
      field-collected females, based on scanning electron microscope images. Then,
      adult males that developed from these eggs were identified to species by
      genitalia examination. A detailed description of diagnostic features of the
      operculum is given for each of four Orius species: O. albidipennis (Reuter), O.
      niger Wolff, O. laevigatus (Fieber), and O. horvathi (Reuter). Characterizing the
      structure of egg opercula of additional Orius species would facilitate ecological
      and biological control research in other parts of the world.

PMID- 23156146
TI  - Interactive influence of temperature and relative humidity on egg parasitoids of
      Riptortus pedestris (Hemiptera: Alydidae).
AB  - Previous studies reported that of the two egg parasitoids of Riptortus pedestris
      (F.) (Hemiptera: Alydidae) found in Korea, Gryon japonicum (Ashmead)
      (Hymenoptera: Scelionidae) appears in soybean fields much earlier than Ooencyrtus
      nezarae Ishii (Hymenoptera: Encyrtidae). To explain this phenomenon, we evaluated
      the interactive influence of temperature and relative humidity (RH) on the
      biological attributes of these parasitoids, including adult parasitoid longevity
      and survival. Temperature had significant effects on all the biological
      attributes examined for both parasitoids, while RH only affected rates of
      parasitism and adult emergence. Interaction between temperature and species, but
      not RH and species was found to affect significantly on parasitism. G. japonicum
      showed higher relative increment in parasitism than O. nezarae at temperatures
      higher than 25 degrees C. No significant differences in progeny sex ratio were
      detected for either species at any temperature x humidity combination. RH had no
      effect on the developmental time of O. nezarae but on the developmental time of
      G. japonicum, which was longer at low RH. Although the biological attributes of
      adult parasitoids of both species showed a wide range of adaptability, but it did
      not explain the patterns of occurrence of these species in the field. However, G.
      japonicum showed greater longevity than O. nezarae at all combinations of
      temperature and RH and this may partially explain the seasonal pattern of
      occurrence of adult parasitoids in the field previously observed.

PMID- 23156147
TI  - Biology of Pseudoligosita plebeia (Hymenoptera: Trichogrammatidae), an egg
      parasitoid of Homalodisca spp. (Hemiptera: Cicadellidae) collected from
      northwestern Mexico as a potential biocontrol agent of H. Vitripennis in
      California.
AB  - Pseudoligosita plebeia (Perkins) (Hymenoptera: Trichogrammatidae) is a candidate
      biological control agent targeting the glassy-winged sharpshooter, Homalodisca
      vitripennis (Germar) (Hemiptera: Cicadellidae), in California. Little is known
      about the biology of P. plebeia. Here we report the results of laboratory studies
      describing the longevity of P. plebeia adults provided alternative food
      resources, their ability to parasitize H. vitripennis eggs of different ages,
      lifetime offspring production when provided steady access to excess host eggs,
      and levels of mature ovarian eggs present when wasps were held without access to
      hosts. P. plebeia is a gregarious parasitoid, with up to six adults emerging from
      a single H. vitripennis egg. When provided with honey and water, water alone, or
      no food or water, P. plebeia adult females lived an average of 64.1, 2.3, and 2.0
      d, respectively. P. plebeia were able to successfully parasitize all ages of H.
      vitripennis eggs (1-8 d old), with higher parasitism in younger host eggs (1-3 d
      old) than in older host eggs (5-7 d old). An increasing trend in offspring
      production was seen for P. plebeia from adult age 2-26 d followed by a decreasing
      trend with offspring produced up to age 75 d. P. plebeia females are at least
      partially synovigenic, as they contained fewer mature eggs at younger ages (1 and
      3 d old) than at older ages (5, 11, 15, and 31 d old). Our results provide
      foundational information regarding the biology of P. plebeia useful for its
      further evaluation as a potential biological control agent in California.

PMID- 23156148
TI  - Controlled atmosphere and temperature treatment system to disinfest fruit moth,
      Carposina sasakii (Lepidoptera: Carposinidae) on apples.
AB  - Carposina sasakii Matsumura (Lepidoptera: Carposinidae) is a serious pest of
      apples and peaches in Korea and Japan. Because of its limited distribution, C.
      sasakii has been identified as a quarantine pest in several countries. The
      Controlled Atmosphere/Temperature Treatment System (CATTS) was tested as an
      alternative to methyl bromide fumigation to control C. sasakii in apples. The
      fifth instar was the most tolerant immature stage to a heat treatment of 44
      degrees C for 20 min. When the apples infested with different stages of C.
      sasakii were treated under CATTS conditions (heating rate of 16 degrees C/h,
      chamber temperature of 46 degrees C, final core temperature of 44 degrees C under
      1% O2/15% CO2 atmosphere), young larvae (first-fourth instars) did not survive
      after 40 min exposure, but the fifth instars required an exposure of at least 60
      min to attain 100% mortality. A partial heat shock protein 90 (hsp90) was cloned
      and showed inducible expression in response to heat shock at 44 degrees C. CATTS
      suppressed transcription of the hsp90 gene. Apples did not show any appreciable
      loss of quality in relation to fruit firmness, sweetness, and decay after a 60
      min CATTS treatment. These results suggest that CATTS can be applicable to
      control C. sasakii in apples.

PMID- 23156149
TI  - Integration of insecticidal, phagostimulatory, and visual elements of an attract
      and kill system for apple maggot fly (Diptera: Tephritidae).
AB  - The apple maggot fly, Rhagoletis pomonella (Walsh), is a key pest of apple in
      eastern North America that has been historically controlled with organophosphate
      insecticide applications. Here we report on progress toward development of an
      effective and maintenance-free attracticidal sphere system for this pest species.
      In our studies, we evaluated lethality of spinosad in combination with a feeding
      stimulant (sucrose) to replace a Tangletrap sticky coating as the killing agent
      of a sphere-based behavioral control system. Spinosad was incorporated into
      cylindrical and contoured controlled-release caps that were fixed atop visually
      stimulating sphere bases. For both cap styles, spinosad at or near 1.0% (a.i.)
      proved to be a relatively durable fly-killing agent, providing approximately
      equal to 85% mortality after simulated rainfall exposure reflective of average
      season-long precipitation levels experienced during the primary period of risk of
      apple maggot injury to fruit in the northeastern United States. In field trials,
      we assessed the impact of color degradation of contoured controlled-release caps
      on visual responsiveness of apple maggot fly and found that it had no significant
      impact on captures. In commercial orchard trials designed to evaluate the
      potential of attracticidal spheres with contoured caps for direct control of
      apple maggot, a perimeter-based deployment provided protection comparable to
      plots receiving 1-2 whole-plot insecticide applications.

PMID- 23156150
TI  - Field trials of solid triple lure (trimedlure, methyl eugenol, raspberry ketone,
      and DDVP) dispensers for detection and male annihilation of Ceratitis capitata,
      Bactrocera dorsalis, and Bactrocera cucurbitae (Diptera: Tephritidae) in Hawaii.
AB  - Solid Mallet TMR (trimedlure [TML], methyl eugenol [ME], raspberry ketone [RK])
      wafers and Mallet CMR (ceralure, ME, RK, benzyl acetate) wafers impregnated with
      DDVP (2,2-dichlorovinyl dimethyl phosphate) insecticide were measured in traps as
      potential detection and male annihilation technique (MAT) devices. Comparisons
      were made with 1) liquid lure and insecticide formulations, 2) solid cones and
      plugs with an insecticidal strip, and 3) solid single and double lure wafers with
      DDVP for captures of Mediterranean fruit fly, Ceratitis capitata (Wiedemann);
      oriental fruit fly, Bactrocera dorsalis Hendel; and melon fly, B. cucurbitae
      Coquillett. Bucket and Jackson traps were tested in a coffee plantation near
      Eleele, Kauai Island, HI (trials at high populations) and avocado orchards near
      Kona, HI Island, HI (trials at low populations). Captures of all three species
      with Mallet TMR were not different from Mallet CMR; therefore, subsequent
      experiments did not include Mallet CMR because of higher production costs. In MAT
      trials near Eleele, HI captures in AWPM traps with Mallet TMR wafers were equal
      to any other solid lure (single or double) except the Mallet ME wafer. In survey
      trials near Kona, captures of C. capitata, B. cucurbitae, and B. dorsalis with
      Mallet TMR wafers were equal to those for the standard TML, ME, and C-L traps
      used in FL and CA. A solid Mallet TMR wafer is safer, more convenient to handle,
      and may be used in place of several individual lure and trap systems, potentially
      reducing costs of large survey and detection programs in Florida and California,
      and MAT programs in Hawaii.

PMID- 23156151
TI  - Identification and field bioassay of the sex pheromone of Trichophysetis cretacea
      (Lepidoptera: Crambidae).
AB  - The jasmine bud borer Trichophysetis cretacea (Butler) (Lepidoptera Crambidae) is
      an important agricultural pest of jasmine flowers Jasminum sambac in China. The
      extract from the pheromone gland of the female moth was analyzed by gas
      chromatography coupled to mass spectroscopy (GC-MS). (Z)-11-hexadecenyl acetate
      (Z11-16:Ac), (Z)-11-hexadecenal (Z11-16:Ald),and (Z)-11-hexadecenol (Z11-16:OH)
      were identified as the probable sex pheromone components. The electroantennogram
      (EAG) bioassay confirmed the results from the chemical analysis. Field bioassays
      conducted in the late summer and fall in Quanwei, Sichuan, China, showed that the
      synthetic chemical blend of Z11-16:Ac, Z11-16:Ald, and Z11-16:OH was highly
      attractive to male T. cretacea moths, and none of the three components was
      attractive by itself. All three components were necessary and the ratio of the
      three was critical. The highest number of male moths was captured when the ratio
      of Z11-16:Ac: Z11-16:Ald:Z11-16:OH was 10:10:1 at a dosage per lure of 200 microg
      Z11-16:Ac. The binary mixture of 200 microg Z11-16:Ac and 25 microg Z11-16:OH
      captured a number of Nymphicula mesorphna (10.3 +/- 4.4). The results indicate
      that traps with synthetic pheromone lures can be used to monitor jasmine bud
      borer populations in the field and potentially to control this pest.

PMID- 23156152
TI  - Thermal requirements and development of Herpetogramma phaeopteralis (Lepidoptera:
      Crambidae: Spilomelinae).
AB  - ABSTRACT The tropical sod webworm, Herpetogramma phaeopteralis Guenee is a major
      turfgrass pest in the southeastern United States. We evaluated larval development
      on five artificial diets and at six temperatures (15, 20, 25, 30, 32.5, 35 +/- 1
      degree C) on St. Augustinegrass (Stenotaphrum secundatum (Walter) Kuntze). Only
      larvae fed St. Augustinegrass and soy-wheat germ diets completed their
      lifecycles. None of the artificial diets tested (corn-based, soy-wheat germ, corn
      cob-wheat germ, corn cob-soy flour, or pinto bean) were suitable for rearing this
      species, because of high mortality and slower developmental time. Total
      developmental time (oviposition to adult) on S. secundatum significantly
      decreased from 47.8 d at 20 degrees C to 21.1 d at 30 degrees C, and then
      increased to 32.6 d at 32.5 degrees C. Tropical sod webworm failed to complete
      larval development at 15 and 35 degrees C. The relationship between temperature
      and developmental rate was described using linear (common and polynomial) and
      nonlinear models (Briere-1, Briere-2, and Lactin-2). The estimated lower
      temperature thresholds using a linear model for eggs, first, second, third,
      fourth, fifth, and sixth instars, prepupa, pupa, and total development were 10.1,
      6.9, 12.3, 10.5, 15.3, 13.9, 9.1, 13.1, 12.0, and 13.1 degrees C, and the thermal
      constant of these stages were 62.9, 66.2, 38.2, 40.3, 24.9, 32.3, 51.9, 106.4,
      109.9, and 370.4 degree-days, respectively. The Briere-1 model provided the best
      fit with estimated lower, upper, and optimum thresholds for total development of
      14.9, 34.3, and 29.4 degrees C, respectively. The developmental requirements of
      H. phaeopteralis can be used to help predict the distribution and seasonal
      phenology of this pest.

PMID- 23156153
TI  - Temperature-dependent demography of Aulacaspis yasumatsui (Hemiptera:
      Diaspididae).
AB  - Aulacaspis yasumatsui Takagi continues to threaten the extinction of the endemic
      and endangered Cycas taitungensis (Shen et al.) in Taiwan. Failure to understand
      its population demographic parameters in detail will continue to hinder the
      success of pest management practices. An in-depth knowledge of the development,
      survival, and fecundity of A. yasumatsui under different environmental conditions
      is necessary to understand its' population growth. The demography of A.
      yasumatsui was studied in the laboratory based on the age-stage, two-sex life
      table at 20, 23, 25, 28, and 31 degrees C, 70% relative humidity, and a
      photoperiod of 16:8 (L:D) h. The intrinsic rate of increase (r) under these
      temperatures was 0.06, 0.07, 0.09, 0.10, and 0.08 d(-1), respectively. The net
      reproductive rate (R0) was 46.27, 47.78, 69.50, 96.08, and 56.65 offsprings per
      individual and the mean generation time (T) was 65.60, 55.81, 47.82, 44.15, and
      51.42 d, respectively. A. yasumatsui does well at warmer temperatures (25-28
      degrees C); however, its performance is disrupted at lower temperatures. This
      study provides insight on how to minimize growth and destruction of A. yasumatsui
      and conservation of Cy. taitungensis; new cycad reserves should be set up in
      cooler areas in Taiwan.

PMID- 23156154
TI  - The insecticidal activities of fire ant (Hymenoptera: Formicidae) venoms against
      Plutella xylostella (Lepidoptera: Plutellidae) larvae.
AB  - Although fire ants frequently have negative impacts on agricultural systems and
      public health, they have additional beneficial insecticidal effects. To evaluate
      the potential effect of fire ant venoms on agricultural pests, the compositions
      of the venoms and their insecticidal activities against Plutella xylostella (L.)
      larvae were evaluated under laboratory conditions. The alkaloids found in
      Solenopsis geminata (F.) venom are primarily saturated C11, which occur in both
      cis and trans forms, whereas the venom of S. invicta Buren contains six principal
      alkaloids (from trans C1, to C17). Moreover, the proportions of unsaturated
      alkaloids in the venom of polygynous S. invicta were significantly higher than
      the corresponding proportions in the monogynous S. invicta, as shown by our
      previous studies. Fire ant venoms were topically applied to the dorsal thoracic
      region of fourth-instar larvae of P. xylostella. The results of the experiment
      showed that the larval symptoms induced by fire ant venom include contractile,
      flaccid paralysis, black coloration and death. P. xylostella larvae were most
      susceptible to S. geminata venom. The order of the susceptibilities of the larvae
      to the venoms was as follows: S. geminata > S. invicta (monogyne form) > S.
      invicta (polygyne form), as measured by the corresponding LT50 values at 24 h.

PMID- 23156155
TI  - Mexican rice borer (Lepidoptera: Crambidae) injury to corn greater than to
      sorghum and sugarcane under field conditions.
AB  - The Mexican rice borer, Eoreuma loftini (Dyar) (Lepidoptera: Crambidae), is the
      key pest of sugarcane (Saccharum spp.) in Texas; it can attack several grassy
      crop and noncrop host plants and has spread into Louisiana. Through small-plot,
      commercial field, and pheromone trap experiments, this study demonstrates that
      the pest uses corn, Zea mays L., more than sugarcane and sorghum, Sorghum bicolor
      (L.) Moench, but when corn is harvested in late summer, injury to nearby
      sugarcane strongly increases during the next approximately equal to 2 mo to
      harvest. Corn was more infested than sugarcane and sorghum in commercial fields
      regardless of whether sampling occurred on field edges or farther into field
      interiors. Differences in numbers of infested stalks and in numbers of larval
      entry holes between field edges and interiors were not detected. We found that
      Mexican rice borer infestation of corn can cause loss of ears, and lodging,
      shattering, and complete destruction of maturing stalks. The larger quantities of
      adult Mexican rice borers captured in pheromone-based traps placed at corn field
      edges compared with sorghum and sugarcane field edges further indicates that corn
      is preferred to sugarcane and sorghum. The basis for the pest's attraction to
      corn and implications to potential range expansion to other U.S. sugarcane
      growing regions are discussed.

PMID- 23156156
TI  - Early season host plants of Apolygus lucorum (Heteroptera: Miridae) in northern
      China.
AB  - Apolygus lucorum (Meyer-Dur) (Heteroptera: Miridae) has become a severe pest of
      cotton and many other crops in northern China as a result of the widespread
      adoption of Bacillus thuringiensis (Berliner) cotton, with a corresponding
      reduction of broad-spectrum insecticide application in cotton fields. From the
      middle of April to middle June, A. lucorum feeds and develops on other host
      plants before dispersing to cotton fields. Effective suppression of A. lucorum
      populations before they enter cotton fields may be an excellent strategy for
      reducing the occurrence and damage of their subsequent generations in cotton
      fields. For that, basic information about the host plant range of A. lucorum
      during the early season is needed. Between 2006 and 2010, a total of 94 plant
      species from 41 families covering 39,956 square meters of land in natural
      conditions were sampled using the standard white pan beat method. Sixty-six plant
      species, including 45 weeds, 10 fruit trees, 5 timber trees, 4 pasture crops, and
      2 arable crops were found to be hosts of A. lucorum. Among these species,
      Descurainia sophia (L.) Webb ex Prantl, Humulus scandens (Loureiro) Merrill,
      Zizyphus jujuba Miller, Vitis vinifera L., Viciafaba L., and Medicago sativa L.
      were identified as dominant host species because of their wide distribution and
      high population densities of A. lucorum. The results of this study provide useful
      information about the early season host range of A. lucorum, which can be used to
      develop effective strategies to control the pest before its dispersal to cotton
      fields.

PMID- 23156157
TI  - Efficacy and value of prophylactic vs. integrated pest management approaches for
      management of cereal leaf beetle (Coleoptera: Chrysomelidae) in wheat and
      ramifications for adoption by growers.
AB  - Cereal leaf beetle, Oulema melanopus L., can be effectively managed in
      southeastern U.S. wheat, Triticum aestivum L., with scouting and a single
      insecticide treatment, applied at the recommended economic threshold. However,
      many growers eschew this approach for a prophylactic treatment, often tank mixed
      with a nitrogen application before wheat growth stage 30. The efficacy of a
      prophylactic and an integrated pest management (IPM) approach was compared for 2
      yr using small plot studies in North Carolina and regional surveys across North
      Carolina and Virginia. Economic analyses were performed, comparing the total cost
      of management of each approach using the regional survey data. From a cost
      perspective, the prophylactic approach was riskier, because when cereal
      leafbeetle densities were high, economic loss was also high. However, fields
      under the prophylactic approach did not exceed threshold as often as fields using
      IPM. Total cost of prophylactic management was also $20.72 less per hectare,
      giving this approach an economic advantage over IPM. The majority of fields under
      the IPM approach did not exceed the economic threshold. Hence, from an economic
      perspective, both the prophylactic and IPM approaches have advantages and
      disadvantages. This helps explains the partial, rather than complete, adoption of
      IPM by southeastern U.S. wheat growers. Cereal leaf beetle was spatially
      aggregated across the region in 2010, but not in 2011. As a result, from an
      economic standpoint, prophylaxis or IPM may have a better fit in localized areas
      of the region than others. Finally, because IPM adoption is favored when it has a
      strong economic advantage over alternative management approaches, more emphasis
      should be placed on research to reduce costs within the IPM approach.

PMID- 23156158
TI  - Towards integrated pest management in red clover seed production.
AB  - The development of integrated pest management is hampered by lack of information
      on how insect pest abundances relate to yield losses, and how pests are affected
      by control measures. In this study, we develop integrated pest management tactics
      for Apion spp. weevils (Coleoptera: Brentidae) in seed production of red clover,
      Trifolium pratense L. We tested a method to forecast pest damage, quantified the
      relationship between pest abundance and yield, and evaluated chemical and
      biological pest control in 29 Swedish red clover fields in 2008 and 2011. Pest
      inflorescence abundance, which had a highly negative effect on yield, could be
      predicted with pan trap catches of adult pests. In 2008, chemical control with
      typically one application of pyrethroids was ineffective both in decreasing pest
      abundances and in increasing yields. In 2011, when chemical control included
      applications of the neonicotinoid thiacloprid, pest abundances decreased and
      yields increased considerably in treated field zones. A post hoc analysis
      indicated that using pyrethroids in addition to thiacloprid was largely
      redundant. Infestation rates by parasitoids was higher and reached average levels
      of around 40% in insecticide treated field zones in 2011, which is a level of
      interest for biological pest control. Based on the data presented, an economic
      threshold for chemical control is developed, and guidelines are provided on
      minimum effective chemical pest control.

PMID- 23156159
TI  - Crop residue and residue management effects on Armadillidium vulgare (Isopoda:
      Armadillidiidae) populations and soybean stand densities.
AB  - In general, Armadillidium vulgare (Latreille) are considered nonpests of soybean
      [Glycine max (L.) Merrill], but changes in soil conservation practices have
      shifted the pest status of this organism from an opportunistic to a perennial,
      early-season pest in parts of central Kansas. As a result, soybean producers that
      rotate with corn (Zea mays L.) under conservation tillage practices have resorted
      to removing excess corn residue by using controlled burns. In a 2-yr field study
      (2009-2010), we demonstrated that residue removal in burned compared with
      unburned plots (measured as previous crop residue weights) had minimal impact on
      numbers of live and dead A. vulgare, soybean seedling emergence, and isopod
      feeding damage over time. Specifically, removal of residue by burning did not
      result in higher emergence rates for soybean stands or less feeding damage by A.
      vulgare. In a separate study, we found that number of live A. vulgare and residue
      weights had no consistent relationship with seedling emergence or feeding damage.
      Furthermore, seedling emergence was not impacted by higher numbers ofA. vulgare
      in unburned plots, indicating that emergence in this study may have been
      influenced by factors other than A. vulgare densities. These studies demonstrate
      that removing residue through controlled burning did not impact seedling
      emergence in presence of A. vulgare and that residue and feeding damage to
      seedlings did not consistently relate to A. vulgare densities. Other factors that
      may have influenced a relationship between residue and live isopod numbers, such
      as variable moisture levels, are discussed.

PMID- 23156160
TI  - Preference of Formosan subterranean termites for blue-stained southern yellow
      pine sapwood.
AB  - Little research has been conducted to investigate interactions between the
      invasive Formosan subterranean termite, Coptotermes formosanus Shiraki, and pine
      bark beetles native to the southeastern United States. Facilitative interactions
      between these organisms could alter stand dynamics and impact wood utilization
      strategies. American Wood Protection Association Standard E1-09 choice tests were
      carried out to determine the feeding preference of Formosan subterranean termites
      for blue-stained versus unstained southern yellow pine sapwood. Three separate
      colonies of Formosan subterranean termites consumed on average twice as much air
      dried blue-stained southern yellow pine sapwood over unstained air-dried
      controls. Additionally, Formosan subterranean termites consumed over five-times
      more kiln-dried blue-stained sapwood than unstained kiln-dried control wafers.
      The implications of these results are particularly relevant to pine forest
      ecology, nutrient cycling, and the utilization of blue-stained southern pine
      building products in the southeastern United States, where Formosan subterranean
      termites have become established.

PMID- 23156161
TI  - Retail firewood can transport live tree pests.
AB  - Untreated firewood can harbor destructive insects and pathogens and transport
      them to uninfested areas. In a national survey of retail locations selling
      firewood in 18 states, over half (52%) of the firewood was from sources out of
      the purchase state and 50% showed evidence of insect infestation. In a three
      state survey of southern Rocky Mountain retailers, the most common retailer types
      carrying firewood were grocery stores and department or big box stores followed
      by gas stations or convenience stores. In 2007-2009, we purchased 419 firewood
      bundles from retailers in Colorado, New Mexico, Utah, and Wyoming and caged the
      firewood to quantify insect emergence. Live insects emerged from 47% of firewood
      bundles over 18 mo of rearing time. Approximately 11 insects emerged on average
      from each infested bundle (1-520 per bundle). Pine, fir, and mixed-conifer
      bundles yielded the greatest number of insects. Beetles (Coleoptera) were
      prominent and made up the majority of individuals (3-60 individuals in each of 24
      families). Most Coleoptera were bark and ambrosia beetles (subfamily Scolytinae)
      while wood borers (Buprestidae, Cerambycidae, Siricidae) occurred in lower
      numbers. Firewood with evidence of previous or current insect infestation was
      more likely to have insects emerge than firewood without such evidence. The risk
      of moving live native or nonindigenous insects in untreated firewood is high
      because insects emerged up to 558 d from purchase date. Retail firewood should be
      heat treated in a manner to eliminate insects that is uniformly accepted across
      North America.

PMID- 23156162
TI  - Spatial dynamics of the invasive defoliator amber-marked birch leafminer across
      the Anchorage landscape.
AB  - The amber-marked birch leafminer (Profenusa thomsoni [Konow]) (Hymenoptera:
      Tenthredinidae) has caused severe infestations of birch species in Anchorage, AK,
      since 2002. Its spatial distribution has been monitored since 2006 and summarized
      using interpolated surfaces based on simple kriging. Results indicate that this
      insect pest is unevenly distributed, occurring in multineighborhood sized patches
      that migrate from year to year. Patches showing heavy infestation one year are
      followed by light infestations the following year. In this study, we developed
      methods of assessing and describing spatial distributions of P. thomsoni as they
      vary from year to year, and speculate on potential causes of these trends in
      landscape patterns.

PMID- 23156163
TI  - Efficacy of "Verbenone Plus" for protecting ponderosa pine trees and stands from
      Dendroctonus brevicomis (Coleoptera: Curculionidae) attack in British Columbia
      and California.
AB  - The western pine beetle, Dendroctonus brevicomis LeConte (Coleoptera:
      Curculionidae, Scolytinae), is a major cause of ponderosa pine, Pinus ponderosa
      Douglas ex Lawson, mortality in much of western North America. We review several
      years of research that led to the identification of Verbenone Plus, a novel four
      component semiochemcial blend [acetophenone, (E)-2-hexen-1-ol + (Z)-2-hexen-1-ol,
      and (-)-verbenone] that inhibits the response of D. brevicomis to attractant
      baited traps, and examine the efficacy of Verbenone Plus for protecting
      individual trees and forest stands from D. brevicomis infestations in British
      Columbia and California. In all experiments, semiochemicals were stapled around
      the bole of treated trees at approximately equal to 2 m in height. (-)-Verbenone
      alone had no effect on the density of total attacks and successful attacks by D.
      brevicomis on attractant-baited P. ponderosa, but significantly increased the
      percentage of pitchouts (unsuccessful D. brevicomis attacks). Verbenone Plus
      significantly reduced the density of D. brevicomis total attacks and D.
      brevicomis successful attacks on individual trees. A significantly higher
      percentage of pitchouts occurred on Verbenone Plus-treated trees. The application
      of Verbenone Plus to attractant-baited P. ponderosa significantly reduced levels
      of tree mortality. In stand protection studies, Verbenone Plus significantly
      reduced the percentage of trees mass attacked by D. brevicomis in one study, but
      in a second study no significant treatment effect was observed. Future research
      should concentrate on determining optimal release rates and spacings of release
      devices in stand protection studies, and expansion of Verbenone Plus into other
      systems where verbenone alone has not provided adequate levels of tree
      protection.

PMID- 23156164
TI  - Seasonal phenology of Ferrisia gilli (Hemiptera: Pseudococcidae) in commercial
      pistachios.
AB  - The mealybug Ferrisia gilli Gullan is a serious new pest of pistachios in
      California. It was first found near the town of Tulare in the late 1990s and has
      since spread to orchards in most pistachio-producing regions of the state. The
      seasonal phenology of F. gilli was evaluated in a commercial pistachio orchard in
      Tulare County during 2005 and 2006. During both seasons E gilli overwintered as
      small nymphs and had three complete generations per year. Mealybug population
      densities were low and remained as immatures in March and April; by late May
      adult females formed and averaged (+/- SE) 1.3 +/- 0.3 and 1.2 +/- 0.3 per 0.75 m
      of sample branch in 2005 and 2006, respectively. The first in-season generation
      occurred from early June through mid-July, with mealybug densities ranging from
      17.6 +/- 5.6-26.4 +/- 6.2 mealybugs per 0.75 m sample branch. The second in
      season generation occurred from late July through September and had peak
      densities of 408.6 +/- 93.9 and 182.0 +/- 34.2 mealybugs per branch. In March and
      April mealybugs were located primarily on the buds and branch wood; in May the
      population was on branch wood as well as the rachis; from June through September
      the population was located primarily in the pistachio cluster. F. gilli's
      seasonal phenology described herein was used to develop a management program.

PMID- 23156165
TI  - Rainfastness of insecticides used to control Japanese beetle in blueberries.
AB  - Field-based bioassays were used to determine the relative impact of rainfall on
      the relative toxicity of four insecticides, phosmet, carbaryl, zeta-cypermethrin,
      or imidacloprid, from different chemical classes on adult Japanese beetles,
      Popillia japonica Newman, in highbush blueberries, Vaccinium corymbosum L.
      Bioassays were set up 24 h after spraying occurred and Japanese beetle condition
      was scored as alive, knockdown or immobile 1, 24, and 48 h after bioassay setup.
      All insecticides were significantly more toxic than the untreated control and
      zeta-cypermethrin consistently had the greatest toxic effect against the Japanese
      beetles. All insecticides experienced a decrease in efficacy after simulated
      rainfall onto treated blueberry shoots, although the efficacy of zeta
      cypermethrin was the least affected by rainfall. This study will help blueberry
      growers make informed decisions on when reapplications of insecticides are needed
      in the field with the aim of improving integrated pest management (IPM).

PMID- 23156166
TI  - Communication disruption of Epiphyas postvittana (Lepidoptera: Tortricidae) by
      using two formulations at four point source densities in vineyards.
AB  - Light brown apple moth [Epiphyas postvittana (Walker)] is now established as an
      economic and quarantine pest in California, and new technologies are being
      investigated to increase options for its management. Two new organic formulations
      for mating disruption, SPLAT LBAM HD-O and organic Hercon Biotie (biodegradable)
      were field tested at four point source densities (25, 72, 322, and 500/ha) and
      compared with the standard Isomate LBAM Plus (500/ha, as a positive control) and
      an untreated (negative) control. Assessment involved trapping using synthetic
      lures and virgin females. In total, 175,776 male light brown apple moths were
      caught to both the caged females and synthetic lures, from 10 February to 19 May
      2011. The light brown apple moth catch dramatically decreased from baseline
      measurements after the treatments were applied, with the highest density
      treatments reducing catch to below 10% of the catch in the untreated controls
      within the first week (> 90% disruption). In synthetic lure traps, the SPLAT and
      Biotie treatment performed similarly well over all rates (P = 0.317 for
      posttreatment percentage communication disruption), but SPLAT performed better at
      disrupting virgin female traps (P = 0.045). There was a significant increase in
      disruption with an increasing number of points/ha (P < 0.001). Disruption of
      communication was similar for all three technologies (SPLAT, Biotie and Isomate)
      at 500 points/ha for both types of trap (P > 0.74). Disruption of this species in
      vineyards is thus highly feasible.

PMID- 23156168
TI  - Whole-farm mating disruption to manage Grapholita molesta (Lepidoptera:
      Tortricidae) in diversified New Jersey orchards.
AB  - Fruit orchards in New Jersey are usually isolated from neighboring farms and
      diversified, often containing separate plantings of peach (Prunus spp.) and apple
      (Malus spp.). These crops can suffer significant damage from oriental fruit moth,
      Grapholita molesta (Busck) (Lepidoptera: Tortricidae). This study evaluated the
      effect of managing G. molesta by using sex pheromone-based mating disruption
      applied to both peaches and apples (whole-farm mating disruption) rather than
      treating either crop alone. In year 1 of the experiment, G. molesta mating
      disruption applied to the adjacent peach and apple blocks provided better control
      than treating peaches or apples alone. During year 2, treating these adjacent
      blocks or only treating apples controlled G. molesta equally well. G. molesta
      populations were so low at the end of year 2 that mating disruption was not
      applied against this pest during year 3. This allowed us to determine whether
      applying mating disruption for two consecutive years controlled G. molesta well
      enough that it eliminated the need mating disruption for three consecutive years.
      The mean cumulative number of G. molesta captured in plots where both peaches and
      apples had been treated did not exceed two moths per trap in the third year of
      this experiment. In contrast, G. molesta capture rebounded during August in
      peaches and apples that had not been treated with mating disruption the previous
      2 yr. Implications for managing G. molesta by using mating disruption as a "whole
      farm" tactic as well applying it for two consecutive years and not a third year
      are discussed.

PMID- 23156167
TI  - Field efficacy and application timing of methoxyfenozide, a reduced-risk
      treatment for control of navel orangeworm (Lepidoptera: Pyralidae) in almond.
AB  - Large-scale field efficacy trials of methoxyfenozide (Intrepid), a reduced-risk
      molting agonist insecticide, were conducted in 2004 and 2005 in an orchard
      containing 'Nonpareil' and 'Sonora almonds [Prunus dulcis (Mill.) D.A. Webb]
      located in Kern County, CA. Methoxyfenozide applied one to three times, the
      organophosphate phosmet (Imidan) alone or in combination with methoxyfenozide, or
      the pyrethroid permethrin (Perm-Up) were tested for efficacy against the primary
      lepidopteran pest navel orangeworm, Amyelois transitella (Walker) (Lepidoptera:
      Pyralidae), and three other lepidopteran pests of almond: oriental fruit moth,
      Grapholita molesta (Busck); oblique-banded leafroller, Choristoneura rosaceana
      (Harris); and peach twig borer, Anarsia lineatella Zeller. Two or three
      applications of methoxyfenozide (bracketing hull split or spring plus bracketing
      hull split) were more effective than a single hull split application of phosmet,
      phosmet combined with permethrin, or methoxyfenozide. In these trials, a spring
      application followed by a posthull split application was as effective as the
      applications bracketing hull split. Navel orangeworm accounted for > 60% of the
      total damage, whereas oriental fruit moth and peach twig borer were the dominant
      secondary pests. In experiments conducted in 2010 to assess the direct toxicity
      of methoxyfenozide to navel orangeworm eggs under field conditions, exposure to
      methoxyfenozide reduced survival by 96-99%. We conclude that this reduced-risk
      insecticide is effective, although its efficacy is maximized with more than one
      well-timed application.

PMID- 23156169
TI  - Evaluation of the predation capacity of Podisus maculiventris (Hemiptera:
      Pentatomidae) on Microtheca ochroloma (Coleoptera: Chrysomelidae) in field cages.
AB  - The predation capacity of the spined soldier bug, Podisus maculiventris (Say)
      (Hemiptera: Pentatomidae), was evaluated at three release rates in field cages
      containing larvae of the yellowmargined leaf beetle, Microtheca ochroloma Stal
      (Coleoptera Chrysomelidae), a pest of organic crucifer (Brassicaceae) crops in
      the United States. The experiment was conducted twice, in February-March 2009 and
      in February-March 2010. On the same day as the introduction of 132 first instars
      of M. ochroloma into the cages, four (= low), 10 (= medium), or 16 (= high) first
      instars of P. maculiventris were released evenly among six turnip (Brassica rapa
      L.) plants in cages. Control treatment cages received no predators. In 2009, the
      mean number of M. ochroloma larvae declined progressively during the first four
      sampling dates. On the final (seventh) sampling date, the mean numbers of total
      M. ochroloma in the two higher release-rate treatments were significantly lower
      than in the low release-rate and control treatments. Overall survivorship of P.
      maculiventris was 39.1% in the high release-rate treatment. In 2010, the mean
      number of M ochroloma larvae declined progressively during the first four
      sampling dates. On the fourth sampling date and the final (ninth) sampling date,
      there were no significant differences among treatments involving predator
      releases. The lowest overall survivorship of P. maculiventris (3.1%) was in the
      high release-rate treatment. Two tentative recommendations for growers emerged
      from this study: 1) release 10 first instars of P. maculiventris per six plants
      if the plants are expected to have > or = 7 leaves per plant; or 2) release four
      first instars of P. maculiventris per six plants if the plants are expected to
      have < or = 6 leaves per plant.

PMID- 23156170
TI  - Impact of insecticides on the invasive Halyomorpha halys (Hemiptera:
      Pentatomidae): analysis of insecticide lethality.
AB  - The efficacy of 37 insecticide treatments against adult Halyomorpha halys (Stal)
      was established based on exposure to 18-h old dry insecticide residue in
      laboratory bioassays. Individual adult H. halys were exposed to an insecticide
      residue for 4.5 h and then monitored daily for survivorship over a 7-d period.
      The proportion of dead and moribund insects was used as an estimate of overall
      insecticide efficacy against H. halys immediately after the exposure period and
      over the 7-d trial. Among all materials evaluated, 14 insecticides exhibited
      increasing efficacy, in which the percentage of dead and moribund insects (used
      as a measure of insecticide efficacy) increased by > 10% after 7 d. By contrast,
      insecticide efficacy values of eight insecticides declined by > 10% (based on
      recovery of adults from a moribund state) over the 7-d period with most belonging
      to the pyrethroid class. In this study, the efficacy value of neonicotinoid,
      acetamiprid, showed the greatest decline from 93 to 10% over 7 d. A lethality
      index (scale of 0-100) was developed to compare insecticides based on quantifying
      the immediate and longer-term effects of insecticide exposure on H. halys. Among
      all materials evaluated, dimethoate, malathion, bifenthrin, methidathion,
      endosulfan, methomyl, chlorpyrifos, acephate, fenpropathrin, and permethrin
      yielded the highest values (> 75) because of a high degree of immediate mortality
      with very little recovery. Our results provide baseline information regarding
      potential of candidate insecticides against adult H. halys and highlight the need
      to consider longer-term effects in establishing overall efficacy ratings against
      this invasive species.

PMID- 23156171
TI  - Toxicity and horizontal transfer of chlorantraniliprole in the eastern
      subterranean termite.
AB  - Toxicity and horizontal transmission of chlorantraniliprole were measured against
      field-collected eastern subterranean termites, Reticulitermes flavipes (Kollar).
      Chlorantraniliprole was highly toxic to termite workers in brief and continuous
      exposure assays across arange of concentrations from 5 to 100 ppm. All doses
      tested resulted in 100% mortality in the termites in 14 d. The effect of exposure
      route (topical, oral, or both) was investigated by exposing termites to treated
      substrate only, treated food only, or both. Results indicate that exposure route
      has no significant effect on chlorantraniliprole toxicity and demonstrate that
      chlorantraniliprole is highly active by feeding and contact. Results of feeding
      assays (paper consumption tests) demonstrate that as little as 5-ppm
      chlorantraniliprole applied to sand prevents termites from consuming cellulose
      that is in contact with the treated sand. Termites on untreated soil consumed 79
      +/- 3% of the available paper in 3 d, whereas termites on chlorantraniliprole
      treated did not consume any paper before they became symptomatic and died.
      Results of transfer tests demonstrate that chlorantraniliprole is transferred
      efficiently among the termites. The rate and the level of secondary mortality in
      the recipient termites depend on both the concentration of chlorantraniliprole
      and the duration of exposure in the donors. Little secondary mortality was
      observed with the lowest dose of 5 ppm, which was effective at killing the donor
      termites, but insufficient to cause mortality in the recipient termites. In
      contrast, highly efficient transfer was observed with 25 and 50 ppm
      chlorantraniliprole. Both doses resulted in 100% mortality in the donors and the
      recipients at 21 d after exposing the recipients to the treated donors. These
      data demonstrate that chlorantraniliprole has dose-independent toxicity, delayed
      toxicity, and is readily transferred in eastern subterranean termites.

PMID- 23156172
TI  - Potential of natural products and their derivatives to control Formosan
      subterranean termites (Isoptera: Rhinotermitidae).
AB  - Twenty-nine natural products and their derivatives were tested for both contact
      and vapor toxicity against the Formosan subterranean termite, Coptotermes
      formosanus Shiraki (Isoptera: Rhinotermitidae). Five natural products at 0.5%
      (wt:wt) in petri dish contact assay caused 100% mortality within 3 d. In vapor
      form, only three chemicals (styrallyl alcohol, 2-phenyl-2-propanol, and l
      carvone) at 0.25 microl/liter air caused > 90% mortality in 3 d when tested on
      exposed termites: However, when termites were shielded by wood and soil, only one
      chemical, tetrahydrocarvone at 25 microl/liter air caused 100% mortality in 2 d.
      Preliminary test with termites in carton nests, exposed to tetrahydrocarvone
      vapor in desiccators, resulted in an average of 98.6% mortality in 7 d. With
      further development in the method of delivery, this chemical may be very useful
      in fumigating confined areas of termite infestation.

PMID- 23156173
TI  - Effect of scattered and discrete hydramethylnon bait placement on the Asian
      needle ant.
AB  - The Asian needle ant (Pachycondyla chinensis Emery) is invading natural and
      disturbed habitats across the eastern United States. While recent studies
      document the impact of P. chinensis on native ecosystems and human health,
      effective control measures remain unknown. Thus, we evaluated the field
      performance of a hydramethylnon granular bait, Maxforce Complete Granular Insect
      Bait, dispersed in clumps or scattered against P. chinensis. We also measured the
      effect of this bait on P. chinensis outside of the treatment zone. Surprisingly,
      unlike reports for other ant species, we achieved nearly complete P. chinensis
      population reductions 1 d after treatments were applied. Significant ant
      reductions were achieved until the end of our study at 28 d. No difference was
      recorded between clumped and scattered application methods. We found no overall
      difference in ant reductions from the edge out to 5 m beyond the treatment zone.
      Other local ant species appeared to be unaffected by the bait and foraging
      activity increased slightly after P. chinensis removal from treated areas. We
      suggest that Maxforce Complete Granular Insect Bait can be effective in an Asian
      needle ant treatment program.

PMID- 23156174
TI  - Evaluation of three bait materials and their food transfer efficiency in Formosan
      subterranean termites (Isoptera: Rhinotermitidae).
AB  - The consumption and food transfer efficiency of two commercially used termite
      bait materials, southern yellow pine wood and cardboard, and one potential bait
      material, maize (Zea mays L.) cob, were evaluated for use against the Formosan
      subterranean termite, Coptotermes formosanus Shiraki (Isoptera: Rhinotermitidae),
      in the laboratory. In the no-choice test, the consumption of wood and cob was
      similar and significantly more than cardboard. Tunneling under the food sources
      was similar. In the two-choice test, the consumption was cob > wood, wood >
      cardboard, cob = cardboard, and tunneling under these choices was cob = wood,
      wood = cardboard, cob > cardboard. In the three-choice test, no significant
      difference was detected in consumption, but tunnels made under the cob were
      significantly more than wood and cardboard. Nile blue A was used to study food
      transfer of bait material among termite cohorts. Dyed cardboard, cob, or wood
      (0.1% Nile blue A) was provided to termites as food. Termites feeding on wood
      turned blue in significantly greater number at 6 h compared with cardboard and
      cob, but there was no significant difference after 12 h. Blue termites feeding on
      different bait materials were then collected and combined with undyed termites.
      When undyed (white) termites were placed with blue termites and food (wood
      block), termites turned blue in the same percentage regardless of original bait
      material fed on. However, when no food was provided (starvation group), the rate
      of white termites turning blue was dramatic; in dyed wood treatment,
      significantly more termites turned blue than that of cardboard, although neither
      were significantly different from cob. Our study is the first to show that, cob,
      an otherwise waste product of the food and biofuel industry, is as efficient as
      wood and cardboard as a termite bait matrix.

PMID- 23156175
TI  - Toxicity and horizontal transfer of 0.5% fipronil dust against Formosan
      subterranean termites.
AB  - The toxicity and horizontal transfer of a new formulation of fipronil, 0.5%
      fipronil dust, was tested against Coptotermes formosanus Shiraki in the
      laboratory. The formulation was applied in three different ways: 1) Directly
      applied to termites (donors) and mixed with untreated termites (recipients) at
      three ratios, viz., 50 donors: 50 recipients, 20 donors: 80 recipients and 10
      donors: 90 recipients. 2) Applied onto the surface of 3 mm thick sand or soil
      substrate in a petri dish and then topped with another 3 mm thick sand or soil
      layer whereupon termites were released. 3) Applied to the inner surface of a tube
      (either 5 cm or 15 cm long) that connected two foraging dishes, one containing
      dry sand and the other moist sand plus a wood block and termites were released
      into the dry sand dish. All donors and >93% of the recipients were dead by 42 h
      after treatment in the direct treatment experiment. Significant mortalities of
      both donors and recipients were observed at 5 h after treatment at all donor:
      recipient ratios. During this period, the mortality of the recipients (but not
      donors) at 10:90 was significantly lower than those at the other two ratios. All
      termites were dead at 65 h after exposure (HAE) on the sand treatment and at 190
      HAE on soil treatment. More than 96% mortality was observed at 40 HAE on the sand
      treatment as compared with only 6% mortality onsoil treatment during the same
      time period. In the tube treatment experiment, > 97% mortality was observed at 90
      h after release for both tube lengths as compared with < 3% mortality in
      controls. About half of the termites were dead by 15 h after release regardless
      of the tube length. Our results showed that 0.5% fipronil dust is nonrepellent
      and readily transferred from treated to nontreated termites.

PMID- 23156176
TI  - Bt pollen dispersal and Bt kernel mosaics: integrity of non-Bt refugia for
      lepidopteran resistance management in maize.
AB  - Field trials were conducted at Rosemount, MN in 2009 and 2010, to measure pollen
      movement from Bt corn to adjacent blocks of non-Bt refuge corn. As the use of Bt
      corn hybrids continues to increase in the United States, and new insect
      resistance management (IRM) plans are implemented, it is necessary to measure the
      efficacy of these IRM plans. In Minnesota, the primary lepidopteran pests of corn
      include the European corn borer, Ostrinia nubilalis (Hubner) and corn earworm,
      Helicoverpa zea (Boddie). The primary IRM plan in transgenic corn is the use of
      hybrids expressing a high dose of insecticidal proteins and an insect refuge
      containing hybrids not expressing insecticidal proteins that produce susceptible
      insects. Wind-assisted pollen movement in corn occurs readily, and is the primary
      method of pollination for corn. The combination of pollen movement and viability
      determines the potential for cross pollination of refuge corn. In 2009 and 2010,
      cross pollination occurred with the highest frequency on the north and east sides
      of Bt corn fields, but was found at some level in all directions. Highest levels
      of cross pollination (75%) were found within the first four rows (3 m) of non-Bt
      corn adjacent to Bt corn, and in general decreasing levels of cross pollination
      were found the further the non-Bt corn was planted from the Bt corn. A mosaic of
      Bt cross-pollinated kernels was found throughout the ear, but in both years the
      ear tip had the highest percentage of cross-pollinated kernels; this pattern may
      be linked to the synchrony of pollen shed and silking between Bt and non-Bt corn
      hybrids. The dominant wind direction in both years was from WNW. However, in both
      years, there were also prevailing winds from SSW and WSW. Further studies are
      needed to quantify Bt levels in cross-pollinated kernels, measure the Bt dose of
      such kernels and associated lepidopteran pest survival, and measure the impact of
      Bt pollen on lepidopteran pests, particularly when considering the seed mixture
      refuge configuration.

PMID- 23156177
TI  - Concentration-dependent effects of GABA on insensitivity to fipronil in the A2'S
      mutant RDL GABA receptor from fipronil-resistant Oulema oryzae (Coleoptera:
      Chrysomelidae).
AB  - The beetle Oulema oryzae Kuwayama (Coleoptera: Chrysomelidae), an important pest
      of rice, has developed fipronil resistance in Japan. Molecular cloning and
      sequence analysis of O. oryzae RDL gamma-aminobutyric acid (GABA) receptor
      subunit (OO-RDL) genes from fipronil-susceptible and -resistant O. oryzae
      identified the A2'S mutation (index number for the M2 membrane-spanning region).
      To investigate the effect of the A2'S mutation on fipronil resistance, we stably
      expressed the wild-type and mutant OO-RDL homomers in Drosophila Mel-2 cells. A
      membrane potential assay exhibited that the IC50 values of fipronil for
      inhibition of the response to EC80 GABA of the wild-type and A2'S mutant OO-RDL
      homomers were 0.09 microM and 0.11 microM, respectively. However, the IC50 values
      of fipronil for inhibition of the response to EC95 GABA of the wild-type and A2'S
      mutant OO-RDL homomers were 0.11 microM and approximately equal to 5 microM,
      respectively. These results suggest that the GABA concentration is an important
      factor affecting fipronil resistance in O. oryzae carrying the A2'S mutation in
      OO-RDL.

PMID- 23156178
TI  - Susceptibility of Cimex lectularius (Hemiptera: Cimicidae) to pyrethroid
      insecticides and to insecticidal dusts with or without pyrethroid insecticides.
AB  - Relative increases of bed bug, Cimex lectularius L., populations are probably due
      in large measure to their resistance to pyrethroids, which have been used
      extensively against urban pests. A Connecticut population of bed bugs was
      assessed for sensitivity to pyrethroids and exposed to commonly-used commercial
      insecticides applied to various substrates on which the residues were allowed to
      age for 0-24 wk. Type I and type II pyrethroids differed in toxicity when applied
      at a high dosage (1 microg) per bed bug. Some type II pyrethroids (cyfluthrin,
      lambda-cyhalothrin, cis-cypermethrin, and deltamethrin) caused > 80% mortality,
      whereas exposure to type I pyrethroids caused < 5% mortality over 72 h (with one
      exception, pyrethrins caused 23% mortality). Dust products were not affected by
      residue aging; mortality response over time of exposure closely fit (R2 > 0.95)
      an exponential rise to a maximum model from which the survival half-life (S1/2)
      was calculated directly. Tempo Dust (Bayer Environmental Science, Montvale, NJ)
      killed bed bugs relatively quickly, as did Syloid 244 (Grace Davison, Columbia,
      MD) and Drione (Bayer Environmental Science, Montvale, NJ) on hardboard and
      mattress fabric substrates (S1/2 < 1 d); DeltaDust (Bayer Environmental Science,
      Montvale, NJ) provided a relatively slow kill (S1/2 approximately equal to 3.5
      d). The sprayable pyrethroids, Cyonara 9.7 (Insecticide Control solutions,
      Pasadena, TX) and D-Force HPX Aerosol 0.06% (Waterbury Companies, Waterbury, CT),
      displayed reduced residual toxicity as they aged; the mortality was < 50% on some
      substrates after 4 d. Desiccant dusts, with their physical mode of action and
      long residual activity, appear to be superior to sprayable pyrethroid products
      for killing bed bugs.

PMID- 23156179
TI  - Potential efficacy of olyset mosquito netting against Calliphora nigribarbis
      (Diptera: Calliphoridae) invasion into livestock barns.
AB  - Calliphora nigribarbis Vollenhoven is a possible mechanical transmitter of highly
      pathogenic avian influenza. Based on laboratory tests, we evaluated the efficacy
      of a long-lasting permethrin-treated mosquito netting, known as the Olyset net,
      for the prevention of this species entering livestock barns. Flies were trapped
      in Olyset net cages, and two statistics for knockdown and lethal efficacies were
      obtained. Median knockdown time in the cage (KT50) was estimated to be 341 s for
      females, and median lethal time after exposure to the mesh (LT50) was estimated
      to be 30 s and <15 s for females and males, respectively. These LT50s were faster
      than those measured for anesthetized stationary flies brought in contact with the
      Olyset net (> 120 s for both sexes),indicating that a fly's spontaneous contact
      with the Olyset net accelerates insecticide adhesion. The rate of permethrin
      adhesion to C. nigribarbis after its spontaneous contact with the Olyset net was
      estimated to be 3.7 ng/s for females, in reference to the 50% lethal dose (LD50)
      value (112 ng/female), which was obtained from the topical application bioassay
      of permethrin. The lethality exhibited after brief spontaneous contact with the
      Olyset net suggests its potential utility in poultry farms against C. nigribarbis
      invasion.

PMID- 23156180
TI  - Genetic characterization of North American populations of the wheat curl mite and
      dry bulb mite.
AB  - The wheat curl mite, Aceria tosichella Keifer, transmits at least three harmful
      viruses, wheat streak mosaic virus (WSMV), high plains virus (HPV), and Triticum
      mosaic virus (TriMV) to wheat (Triticum aestivum L.) throughout the Great Plains.
      This virus complex is considered to be the most serious disease of winter wheat
      in the western Great Plains. One component of managing this disease has been
      developing mite resistance in wheat; however, identification of mite biotypes has
      complicated deployment and stability of resistance. This biotypic variability in
      mites and differential virus transmission by different mite populations
      underscores the need to better understand mite identity. However, A. tosichella
      has a history of serious taxonomic confusion, especially as it relates to A.
      tulipae Keifer, the dry bulb mite. Molecular techniques were used to genetically
      characterize multiple A. tosichella populations and compare them to populations
      of A. tulipae. DNA from these populations was polymerase chain reaction amplified
      and the ribosomal ITS2 region sequenced and compared. These results indicated
      limited variability between these two species, but two distinct types within A.
      tosichella were found that corresponded to previous work with Australian mite
      populations. Further work using sequencing of several mitochondrial DNA genes
      also demonstrated two distinct types of A. tosichella populations. Furthermore,
      the separation between these two A. tosichella types is comparable to their
      separation with A. tulipae, suggesting that species scale differences exist
      between these two types ofA. tosichella. These genetic differences correspond to
      important biological differences between the types (e.g., biotypic and virus
      transmission differences). In light of these differences, it is important that
      future studies on biological response differences account for these mite
      differences.

PMID- 23156181
TI  - Comparative life history and fecundity of Phthorimaea operculella (Lepidoptera:
      Gelechiidae) on leaves and tubers of different potato cultivars.
AB  - The potato tuberworm, Phthorimaea operculella (Zeller) (Lepidoptera:
      Gelechiidae), is a noxious pest of the potato crop (Solanum tuberosum L.) in both
      field and storage in tropical and subtropical regions. Survival, development and
      reproduction of the potato tuberworm was compared on leaves and tubers of 10
      common cultivated potato cultivars including Agria, Agata, Almera, Arinda,
      Baneba, Fiana, Marfona, Ramus, Satina, and Volvox at 25 +/- 1 degree C, 65 +/- 5%
      RH and a photoperiod of 14:10 (L:D) h. The results indicated that there were
      significant differences in the larval, pupal, and total developmental periods on
      the various potato cultivars. The total developmental periods varied from 26.6
      (on Baneba) to 29.5 d (on Marfona),and ranged from 27.9 (on Marfona) to 30.5 d
      (on Agria) in the experiments on potato leaves and tubers, respectively. Immature
      survival rates were lowest on Agria (44.1%) and Marfona (40.6%) on potato leaves
      and tubers, respectively. The highest total fecundity was observed on Arinda
      (78.3 eggs) and Ramus (154.8 egg) on potato leaves and tubers, respectively.
      Significantly fewer eggs were laid on Marfona cultivar's leaves (44.6 eggs) and
      tubers (72.9 eggs) than any of the other tested potato cultivars. The female
      reproduction potential on potato leaves was significantly lower than on potato
      tubers. Cluster analysis of the biological parameters of P. operculella on
      different potato cultivars demonstrated that Marfona is partially resistant to
      potato tuberworm. The findings on the susceptibility or resistance of potato
      cultivars could be a fundamental component of integrated pest management programs
      for potato tuberworm.

PMID- 23156182
TI  - Variation in genetics and performance of Dutch western flower thrips populations.
AB  - Invasion of pests may result in local adaptation and the development of biotypes
      specialized in different hosts. In this study, we investigated western flower
      thrips, Frankliniella occidentalis (Pergande), an invasive pest in Europe. Thrips
      from different commercial glasshouse crops within the Dutch Westland and a lab
      culture kept on chrysanthemum were compared. Genetic barcoding was applied for
      the identification of potential western flower thrips cryptic species in the
      Netherlands revealing that all western flower thrips populations studied belonged
      to the "glasshouse" strain reported in California as the only existing species in
      the Netherlands. Feeding and reproduction parameters in leaf disc and whole plant
      bioassays were scored. We detected significant differences in thrips feeding
      among host plants and thrips origin. Host plants differed in average thrips
      damage while thrips from different origins caused similar amounts of damage
      across host plants. In contrast, reproductive success of thrips on all plant
      species depended strongly on thrips origin. The thrips lab culture maintained on
      chrysanthemum obtained the highest levels of reproduction on chrysanthemum.
      Differences among the other thrips populations were relatively small. Amplified
      fragment length polymorphisms analyses were used to study genetic differences
      between western flower thrips populations and confirmed that the lab culture
      population was also genetically the most different of all studied populations.
      The results of the amplified fragment length polymorphisms analyses together with
      the better reproductive performance of thrips on the host plant on which they
      were maintained demonstrate the evolution of a lab biotype specialized in a
      particular host. This finding has potential relevance for future crop control and
      breeding programs.

PMID- 23156184
TI  - Measuring the benefit of biological control for single gene and pyramided host
      plant resistance for Aphis glycines (Hemiptera: Aphididae) management.
AB  - The soybean aphid, Aphis glycines Matsumura (Hemiptera: Aphididae), is an
      economically important pest in the north central United States. In the state of
      Iowa, economically damaging populations occurred in seven of 11 growing seasons
      from 2001 to 2011. The high frequency and economic impact of the soybean aphid
      makes it an ideal candidate for management by using host plant resistance. We
      compared an aphid-susceptible line to near-isolines that contain Rag1 and Rag2,
      both alone and pyramided together, to suppress aphid populations and protect
      yield. Each of four near-isolines, were artificially infested with aphids and
      grown in small plots in which the exposure to natural enemies was controlled by
      the use of cages, resulting in the following treatment groups: natural enemy free
      (only aphids), biocontrol (both aphids and natural enemies), and aphid free (no
      aphids or natural enemies). The seasonal accumulation of aphids and the
      population growth rates were measured for each line and an estimate of yield was
      measured at the end of the season. Soybean aphid population growth rate was
      reduced 20% by natural enemies alone, 44% by pyramided resistance, and 63% by the
      combination of natural enemies and pyramided resistance. This reduction in
      population growth rate resulted in a 99.3% reduction in the pyramid line's
      seasonal exposure to aphids. In the presence of natural enemies, all three
      resistant lines maintained aphid populations below the economic injury level and
      prevented yield loss. This study demonstrates the compatibility of biological
      control with soybean aphid host plant resistance and its utility, especially for
      single resistance gene lines.

PMID- 23156185
TI  - Variation in resistance mechanisms to the green peach aphid among different
      Prunus persica commercial cultivars.
AB  - ABSTRACT Peaches and nectarines are frequently attacked by the green peach aphid
      Myzus persicae (Sulzer), with significant negative impacts on fruit production.
      The genetic variability of resistance to this aphid among commercial cultivars of
      Prunus persica (L.) Batsch and Prunus persica variety nectarina was evaluated in
      this study. In total, 16 cultivars of P. persica were selected to evaluate the
      occurrence and population growth rate of M. persicae in commercial orchards, as
      well as in no-choice and probing behavior laboratory assays. The results showed
      variability between cultivars in resistance and susceptibility to M. persicae,
      with three cultivars exhibiting different signatures of resistance. The peach
      cultivar 'Elegant Lady' exhibited a low occurrence of aphids in the orchard, a
      low rate of growth, moderate leaf-rejection in a no-choice test and a higher
      number and longer period of salivation into sieve elements, suggesting resistance
      at the phloematic level. The nectarine cultivar 'August Red' also exhibited low
      aphid occurrence in the orchard, a low rate of growth, and resistance at the
      prephloem and phloem levels. Finally, the nectarine 'July Red-NS92' exhibited a
      low occurrence of aphids in the orchard, a higher number of rejections in no
      choice assays and no ingestion of phloem during the probing behavior experiments,
      suggesting prephloematic resistance. The rest of the cultivars studied exhibited
      clear susceptibility. Hence, different resistance mechanisms are apparent among
      the studied cultivars. The information gathered in this study regarding the
      resistance to M. persicae may assist breeding programs aimed at increasing aphid
      resistance to peaches and nectarines.

PMID- 23156183
TI  - Evaluation of corn hybrids expressing Cry1F, cry1A.105, Cry2Ab2,
      Cry34Ab1/Cry35Ab1, and Cry3Bb1 against southern United States insect pests.
AB  - Studies were conducted across the southern United States to characterize the
      efficacy of multiple Bacillus thuringiensis (Bt) events in a field corn, Zea mays
      L., hybrid for control of common lepidopteran and coleopteran pests. Cry1F
      protein in event TC1507 and Cry1A.105 + Cry2Ab2 proteins in event MON 89034 were
      evaluated against pests infesting corn on above-ground plant tissue including
      foliage, stalks, and ears. Cry34Ab1/Cry35Ab1 proteins in event DAS-59122-7 and
      Cry3Bb1 in event MON 88017 were evaluated against the larvae of Mexican corn
      rootworm, Diabrotica virgifera zeae Krysan and Smith, which occur below-ground.
      Field corn hybrids containing Cry1F, Cry1A.105 + Cry2Ab2, Cry34Ab1/Cry35Ab1, and
      Cry3Bb1 insecticidal proteins (SmartStax) consistently demonstrated reductions in
      plant injury and/or reduced larval survivorship as compared with a non-Bt field
      corn hybrid. Efficacy provided by a field corn hybrid with multiple Bt proteins
      was statistically equal to or significantly better than corn hybrids containing a
      single event active against target pests. Single event field corn hybrids
      provided very high levels of control of southwestern corn borer, Diatraea
      grandiosella (Dyar), lesser cornstalk borer, Elasmopalpus lignosellus (Zeller),
      and fall armyworm, Spodoptera frugiperda (J.E. Smith), and were not significantly
      different than field corn hybrids with multiple events. Significant increases in
      efficacy were observed for a field corn hybrid with multiple Bt events for
      sugarcane borer, Diatraea saccharalis (F.), beet armyworm, Spodoptera exigua
      (Hubner), corn earworm, Helicoverpa zea (Boddie), and Mexican corn rootworm.
      Utilization of field corn hybrids containing multiple Bt events provides a means
      for managing insect resistance to Bt proteins and reduces non-Bt corn refuge
      requirements.

PMID- 23156186
TI  - Bayesian estimation for the effectiveness of pesticides and repellents.
AB  - In the quantitative estimation of the effectiveness of pesticides and repellents,
      Abbott's correction and similar methods have been used for nearly a century.
      However, the formulas for such corrections have some disadvantages in performing
      range estimations and being used in batched experiments. These disadvantages also
      exist in the estimation of EC50, the chemical concentration that produces 50%
      mortality. In this study, I propose as a solution to these problems a Bayesian
      estimation with a logistic model. This method enables the flexible modeling of
      non-normal variables in complex experimental design, for example, life-death
      response in a batched experiment. Furthermore, if any knowledge about focal
      phenomena exists, it can be used in analyses as a prior distribution, thus
      enhancing the accuracy of the estimation.

PMID- 23156188
TI  - Gender, sex, and health research: developments and challenges.

PMID- 23156187
TI  - Mortality of adult Stomoxys calcitrans fed isolates of Bacillus thuringiensis.
AB  - We examined the ability of five isolates of Bacillus thuringiensis Berliner to
      cause mortality in adult stable flies, Stomoxys calcitrans (L.). Isolates
      Bacillus thuringiensis tolworthi 4L3 (serotype 9), Bacillus thuringiensis
      darmstadiensis 4M1 (serotype 10a10b), Bacillus thuringiensis thompsoni 401
      (serotype 12), Bacillus thuringiensis thuringiensis HD2 (serotype 1), and
      Bacillus thuringiensis kurstaki HD945 (serotype 3a3b3c) were administered to
      adult flies in diets containing blood only, sugar only, and both sugar and blood
      combined. B. t. tolworthi 4L3 had no effect on adult mortality regardless of the
      feeding substrate. The remaining isolates tended to cause the greatest mortality
      when administered in blood alone. B. t. thompsoni 401 was the only isolate that
      consistently caused adult mortality when fed in blood at concentrations ranging
      from 0.21 to 50.0 microg of protein per ml of blood. This isolate also caused
      mortality when applied topically. The time to 50% mortality declined with dose
      and reached a lower asymptote at approximately equal to 1.3 d at an oral dose of
      8.75 microg/ml and at a topical dose of 0.14 microg per fly.

PMID- 23156189
TI  - The gendered ovary: whole body effects of oophorectomy.
AB  - Since oophorectomy in healthy women predates the commercialization of BRCA
      mutations screens, genomics cannot explain entirely why physicians and cancer
      specialists recommend this procedure for women at risk. Rather, one must situate
      the development of reproductive cancer genomics within a broader sociocultural
      context in which researchers bring to bear habits of mind about women,
      reproduction and motherhood. (Happe, 2006, p. 173)

PMID- 23156190
TI  - An integrative review of nurse attitudes towards lesbian, gay, bisexual, and
      transgender patients.
AB  - A growing body of literature suggests that lesbian, gay, bisexual, and
      transgender (LGBT) persons have significant health disparities as compared to
      heterosexuals. Although the reasons for this are complex and multifactorial, one
      area of research has examined the real or perceived negative attitudes of health
      care providers. This integrative review critically appraises and synthesizes data
      from 17 articles regarding nurses' attitudes towards LGBT patients. Every study
      analyzed showed some evidence of negative attitudes. However, the literature
      revealed major limitations, including a paucity of well-designed studies; a
      dearth of qualitative studies; inconsistent use of validated, reliable
      instruments; and a lack of measures examining attitudes towards lesbian,
      bisexual, and transgender persons. Increased knowledge in this area could lead to
      interventions to improve nurses' cultural competency; resource allocation to
      nursing research, education, and services related to LGBT health; and inclusion
      of more LGBT content in nursing curricula.

PMID- 23156191
TI  - Nurses' work with LGBTQ patients: "they're just like everybody else, so what's
      the difference"?
AB  - Informed by critical feminist and queer studies approaches, this article explores
      nurses' perceptions of practice with patients who identify as lesbian, gay,
      bisexual, transgender, or queer (LGBTQ). Qualitative in-depth, semi-structured
      interviews with 12 nurses in Halifax, Nova Scotia, illuminate a range of
      approaches to practice. Most commonly, participants argued that differences such
      as sexual orientation and gender identity do not matter: Everyone should be
      treated as a unique individual. Participants seemed anxious to avoid
      discriminating or stereotyping by avoiding making any assumptions. They were
      concerned not to offend patients through their language or actions. When social
      difference was taken into account, the focus was often restricted to sexual
      health, though some participants showed complex understandings of oppression and
      marginalization. Distinguishing between generalizations and stereotypes may
      assist nurses in their efforts to recognize social differences without harming
      LGBTQ patients.

PMID- 23156192
TI  - Supporting fathers' efforts to be smoke-free: program principles.
AB  - There is limited empirical evidence on effective ways to develop, distribute, and
      evaluate men-centred, gender-sensitive health promotion programs. The purpose of
      this research was to transition qualitative findings on men's smoking into father
      centred cessation interventions. Men's perspectives were gathered in 4 group
      sessions with 24 new fathers who smoked. The data led to the identification of 3
      principles for men's health promotion programs: use positive messaging to promote
      change without amplifying stigma, guilt, shame, and blame; foster connections
      between masculine ideals (e.g., strength, decisiveness, resilience, autonomy) and
      being smoke-free; and privilege the testimonials of potential end-users (e.g.,
      fathers who smoke and want to quit). Experiences drawn from the design and pilot
      testing of a booklet and a group program based on these principles are described.
      The findings can be used to guide nurses in the design and/or delivery of men's
      health promotion programs.

PMID- 23156193
TI  - Reaching adolescent girls through social networking: a new avenue for smoking
      prevention messages.
AB  - Because adolescent girls are being targeted on social networking sites by the
      tobacco industry, new online tobacco control (TC) initiatives are needed. The
      purpose of this interpretive descriptive study was to explore adolescent girls'
      perspectives on the use of social networking sites to deliver TC messages
      targeting young women. Focus groups were conducted with 17 girls aged 16 to 19.
      Seven TC messages were provided for evaluation and as context for discussion
      about the delivery of TC messages on social networking sites. Data were analyzed
      for themes, which included concerns about the effectiveness of current TC
      messages and the stereotypical representations of gender, factors perceived to
      influence the effectiveness of TC messages on social networking sites, and
      suggestions for enhancing the effectiveness of TC messages placed on social
      networking sites. Endorsement of TC messaging on social networking sites suggests
      that this medium is an untapped resource for smoking prevention.

PMID- 23156194
TI  - Understanding gendered expectations and exemptions experienced by male double
      duty caregivers: a qualitative secondary analysis.
AB  - There is growing evidence that family caregivers who are also employed face
      challenges in balancing the multiple demands associated with family caregiving.
      Health professionals who are family caregivers, defined in this study as double
      duty caregivers (DDCs), are expected to use their professional knowledge in the
      provision of family care. The purpose of this qualitative secondary analysis was
      to explore how gendered expectations and exemptions affect the caregiving
      experiences and personal health of male nurses caring for family members. Being a
      male DDC created intersecting gendered expectations and exemptions. These
      coexisting and at times conflicting expectations and exemptions, constituted by
      the overarching theme of the determinants of care, directly influenced the health
      of male DDCs as they experienced tension when negotiating their dual role. The
      findings have direct implications for health-care policy and practice, research,
      and theory development.

PMID- 23156195
TI  - Medication management for nurses working in long-term care.
AB  - In long-term care (LTC), the complexity of residents' conditions and their
      treatment requirements present challenges for nurses managing medications. The
      purpose of this qualitative descriptive study was to explore medication
      management as described by licensed nurses working in LTC. A total of 22 licensed
      nurses from 2 LTC facilities located in the Canadian province of Ontario
      participated in 4 focus groups. Thematic content analysis was used to organize
      data into themes and a conceptual model was developed. The overarching theme was
      that nurses are "racing against time" to manage medications and 3 subthemes
      described how they coped with this important care process: preparing to race,
      running the race, and finishing the race. Barriers to safe medication management
      included time restraints, knowledge limitations, interruptions and distractions,
      and poor communication. The findings can be used to better inform health-care
      providers and to guide future research. They also have the potential to directly
      impact outcomes related to safe medication management in LTC.

PMID- 23156196
TI  - Metaphors and medication: understanding medication use by seniors in everyday
      life.
AB  - The purpose of this study was to explore the use of metaphor by independent
      seniors taking medication for chronic health conditions. Narratives from a larger
      study using grounded theory were analyzed using constant comparative analysis and
      induction. A secondary analysis of the narratives of 21 participants was
      undertaken. Transcripts were read line-by-line and all relevant language was
      highlighted and reviewed with the aim of identifying relationships and themes.
      The narratives revealed a diverse range of metaphoric language. Four categories
      were identified: being shackled, hope, external authority, and communication
      fears. Three additional themes were interwoven into the narratives: aging and
      death, medication personified, and the body as object. The authors conclude that
      metaphor reveals the tension and unresolved dilemmas faced by seniors with regard
      to medication use.

PMID- 23156197
TI  - Access to health care. Foreword.

PMID- 23156198
TI  - Post-reform Medicaid before the court: discordant advocacy reflects conflicting
      attitudes.
AB  - This essay explores the conflicting positions taken by the United States in its
      Medicaid-related briefs before the Supreme Court this October 2011 Term. In
      Douglas v. Independent Living Center, the United States articulated a deferential
      stance toward the states, a position consistent with longstanding states' rights
      concerns in the Medicaid program. On the other hand, the federal government has
      advocated a very broad view of federal authority under the spending power to
      modify and expand Medicaid in Florida v. Health and Human Services. Congress has
      acted in ways that are contradictory regarding Medicaid throughout the program's
      history, and those conflicting attitudes have been accentuated by the executive
      branch's dissonant litigation strategies this term. This essay posits that the
      Court could minimize confusion with narrow holdings in both Douglas and Florida
      v. HHS so as to allow Congress and HHS latitude to resolve their conflicting
      attitudes toward Medicaid as well as the intricacies of conditional spending.

PMID- 23156199
TI  - The challenges of reform for Medicaid managed care.
AB  - This article explores the specific consequences to states as a result of
      expansion of the Medicaid program under PPACA. Jane McCahill and Joseph Van Leer
      explain the history of the Medicaid program, comparing and contrasting Medicaid
      pre-PPACA with Medicaid post-PPACA. The authors examine the use of managed care
      models by state Medicaid programs, describing the various forms of Medicaid
      managed care employed by the states. The authors then detail the significant
      changes resulting to Medicaid under PPACA. Finally, the article reviews the
      Medicaid managed care program in Illinois specifically, focusing on reform of the
      Illinois Medicaid program to be effectuated over the next few years. The authors
      conclude by recommending mechanisms for integration among providers under the
      managed care model in order to contain costs and achieve increased quality of
      care.

PMID- 23156200
TI  - New options to integrate care and financing for persons dually eligible for
      Medicare and Medicaid.
AB  - This paper reviews barriers to clinical and financial integration in services for
      dual eligibles prior to passage of the ACA, identifies models used by states to
      integrate care through contract and waiver authorities available to CMS prior to
      passage of the ACA, describes two new demonstrations proposed by CMS through the
      Medicare-Medicaid Coordination Office and Innovation Center, and discusses
      several new models available for consideration by federal and state policymakers.
      These options draw on experience from existing programs and waivers to provide
      suggested changes to existing programs, as well as a permanent state plan option
      for a fully integrated, capitated care model. This model could be made available
      to states prior to the completion of the demonstration process begun by the
      Medicare-Medicaid Coordination Office and Innovation Center.

PMID- 23156201
TI  - Federal/state tensions in fulfilling Medicaid's purpose.
AB  - Medicaid has been subject to reconsiderations of the proper role of government in
      providing for the health and welfare of populations over recent decades. Over the
      last decade in particular, a number of states have transferred many functions
      that they once performed to private entities, including, in a number of cases,
      express policymaking functions. The Patient Protection and Affordable Care Act
      (ACA) takes some crucial steps towards readjusting the equilibrium of Medicaid.
      Rather than further prioritizing the market in its reforms, it gives the federal
      government stronger charge of Medicaid policy, refocusing the program more
      directly on expanding eligibility and providing secure care for beneficiaries in
      the process. I argue that this reprioritization is in better keeping with the
      purpose of Medicaid, in contradistinction to the market-driven reforms undertaken
      during the Bush administration and sought by some states today. It does, however,
      shift more power from the states to the federal government. This has raised
      concerns not only from states that oppose the new health reform law, but also
      from a number that support it. These two groups of states share a desire for
      greater flexibility in their Medicaid programs than the ACA permits. Yet only one
      of these groups should be permitted to use federal Medicaid funds to make the
      reforms they seek. Federal administrations need to be particularly careful, when
      considering whether to grant state Medicaid waiver requests, to uphold Medicaid's
      purpose of giving lower-income Americans genuine access to the same health care
      that other Americans receive.

PMID- 23156202
TI  - Acute effects of electro-acupuncture (EA) on hippocampal long term potentiation
      (LTP) of perforant path-dentate gyrus granule cells synapse related to memory.
AB  - Acupuncture, a traditional Chinese therapeutic method, has been widely used in
      clinical practice to treat diseases such as stroke, Bell's palsy, Alzheimer
      disease, Parkinson diseases, dysmenorrhea and chronic pain. Mounting lab data had
      suggested that electro-acupuncture could alleviate dementia and restore long term
      potentiation of hippocampus in rat. Clinical data also indicated that electro
      acupuncture could improve electrical activity of brain in vascular dementia
      patients. However, its biological basis and acute effects on hippocampal long
      term potentiation (LTP) remain not well understood. Therefore, we sought to
      investigate whether acute electro-acupuncture (acupoints: ST36 and SP6;
      continuous wave, 2 mV, 2Hz; lasted 20 min) could enhance LTP of perforant path
      dentate gyrus granule cells in anesthetized rat and explore its underlying
      mechanisms. We found that electro-acupuncture could significantly increase PS2/PS
      1 in pair pulse test (P <0.05, inter-pulse interval: 20ms and 90ms). When
      compared to control group, electro-acupuncture could significantly enhance LTP to
      about 234% which was about 143% of that in control group (P <0.05). It suggested
      that electro-acupuncture could modulate the function of interneurons in
      hippocampus hence increase LTP.

PMID- 23156203
TI  - Sedating pediatric dental patients by oral ketamine with alternating bi-lateral
      stimulation of eye movement desensitization and minimizing adverse reaction of
      ketamine by acupuncture and Bi-Digital O-Ring Test.
AB  - Ketamine, besides being an anesthetic agent, is also a strong analgesic that can
      be especially useful for painful procedures. Vivid dreams and nightmare,
      considered as undesirable side effects of ketamine, are rarely encountered when
      administrated orally, making it one of the most desirable oral sedative for
      children because it partially protects the pharyngeal-laryngeal reflex. Besides,
      if used in recommended dosage, it does not suppress the cardiopulmonary function
      as most other sedatives do. Ketamine's bronchodilator effect makes it a good
      sedative for children with asthma, allergies, and hay fever. Alternating bi
      lateral stimulation (ABLS) of eye movement desensitization, applying pre
      operatively before ketamine was found to reduce the post-operative violent
      emergence and behavioral problems. Acupressure at P 6 (Neikuan) acupoint helps to
      decrease nausea and vomiting episodes by ketamine. 36 patients with history of
      unmanageable behavior were sedated with ketamine 3mg/kg and ABLS. To prevent
      possible adverse reaction, Bi-Digital O-Ring Test (BDORT) were used to test all
      patients. ABLS significantly decreased tearful separation from parent. It took 15
      to 20 minutes for ketamine to take effect, peak effect took 20 to 25 minutes.
      Working time ranged from 20 to 40 minutes. Post-operative recovery was more
      pleasant when ABLS was combined with ketamine, acupuncture/acupressure not only
      prevented vomiting and BDORT safeguard the patients from unpredictable untoward
      side effects but also promoting calmness.

PMID- 23156204
TI  - Effects of combining electroacupuncture with general anesthesia induced by
      sevoflurane in patients undergoing supratentorial craniotomy and improvements in
      their clinical recovery profile & blood enkephalin.
AB  - Drug-induced anesthesia combined with electroacupuncture (EA) in patients has
      been put into practice in recent years in China. In this study, we showed the
      effectiveness of EA on the speed of post-operative recovery of patients
      undergoing supratentorial craniotomy and the potential clinical mechanism of EA.
      Dual channel electrical stimulator made by HANS Beijing connected the following
      acupoints respectively: LI4 (Hegu), SJ5 (Waiguan), ST36 (Zusanli), BL63 (Jinmen),
      LR3 (Taichong), and GB40 (Qiuxu). Disperse-dense and symmetric biphasic pulse
      waves were selected, frequency of waves (pulse rates) were 2Hz/100Hz,
      altered/3sec; pulse duration was 0.6ms/0.2ms, 2Hz: 0.6ms, 100Hz: 0.2ms; symmetric
      biphasic pulse wave. We found that the EA-group required 9.62% less sevoflurane
      than the sham EA-group (P<0.05). During recovery from anesthesia, the autonomous
      respiration recovery time, tracheo-tube removal time, eye-opening time, voluntary
      motor recovery time, orientation force recovery time, and the operating-room
      departure time of the EA-group were all significantly shortened 35.86%, 27.07%,
      38.38%, 30.11%, 34.95%, 28.80% than the corresponding sham EA-group, respectively
      (P<0.05). The serum enkephalin values were elevated in the EA group versus the
      sham EA-group.

PMID- 23156205
TI  - Algase's top 10 truths about publishing: a Letterman-esque guide for would-be
      authors of journal articles.

PMID- 23156206
TI  - Health inequities, HIV, and public health practice: examining the role of
      qualitative research.
AB  - Although communicable disease public health practice has traditionally been based
      on numbers (e.g., incidence, prevalence), in the domain of HIV prevention and
      control qualitative research has recently become a more commonly employed data
      collection strategy. Of particular benefit, this approach can supplement the
      numbers which typically underpin public health strategies by generating in-depth
      understandings about how specific populations define, describe, and perceive
      their health and the factors that affect it. However, the use of qualitative
      research in public health must be explored; it cannot simply be accepted without
      reflection or analysis. To guide such an investigation, the work of Michel
      Foucault and Michael Hardt and Antonio Negri is used to examine two previous
      research projects that were undertaken by the author. The outcome of this
      analysis is the somewhat paradoxical conclusion that although qualitative
      research can enhance public health work, it may also be a strategy that generates
      the information that can be used for capturing and normalizing marginalized
      populations. Qualitative research, in other words, may be a technique that can be
      used to achieve biopolitical goals.

PMID- 23156207
TI  - Do social support, stigma, and social problem-solving skills predict depressive
      symptoms in people living with HIV? A mediation analysis.
AB  - Social support, stigma, and social problem solving may be mediators of the
      relationship between sign and symptom severity and depressive symptoms in people
      living with HIV (PLWH). However, no published studies have examined these
      individual variables as mediators in PLWH. This cross-sectional, correlational
      study of 150 PLWH examined whether social support, stigma, and social problem
      solving were mediators of the relationship between HIV-related sign and symptom
      severity and depressive symptoms. Participants completed self-report
      questionnaires during their visits at two HIV outpatient clinics in the
      Southeastern United States. Using multiple regression analyses as a part of
      mediation testing, social support, stigma, and social problem solving were found
      to be partial mediators of the relationship between sign and symptom severity and
      depressive symptoms, considered individually and as a set.

PMID- 23156208
TI  - HIV/AIDS knowledge and self-efficacy among late adolescents in Nepal.
AB  - The purpose of this study was to explore HIV/AIDS knowledge and self-efficacy for
      limiting sexual risk behavior in Nepalese late adolescents attending college. A
      convenience sample of 229 baccalaureate college students completed three
      instruments: demographic, HIV/AIDS knowledge questions and the self-efficacy for
      limiting sexual risk behavior questions. The findings of this study showed that
      Nepalese youth had moderate HIV/AIDS knowledge and a moderate level of self
      efficacy. However, they lacked knowledge in certain aspects of HIV transmission.
      HIV/AIDS knowledge was strongly correlated with self-efficacy for limiting sexual
      risk behavior. There was no statistical difference in HIV/AIDS knowledge and self
      efficacy by gender. However, when each self-efficacy item was analyzed by gender,
      there were significant differences in a few items by gender. ANOVA analysis
      showed no significant differences on HIV/AIDS knowledge and self-efficacy by the
      level of education. The findings of this study indicate that there is a need for
      developing school-based and/or community-based programs that will increase
      HIV/AIDS awareness among youth and help them develop decision making and
      communication skills. It is also important to look at the school and college
      curricula and integrate more HIV/AIDS information in the curriculum.

PMID- 23156209
TI  - Caring in pediatric emergency nursing.
AB  - An environment committed to providing family-centered care to children must be
      aware of the nurse caring behaviors important to parents of children. This
      descriptive study assessed the psychometrics of a revised version of the Caring
      Behaviors Assessment (CBA) and examined nurse caring behaviors identified as
      important to the parents of pediatric patients in a pediatric emergency
      department. Jean Watson's theory of human caring provided the study's theoretical
      underpinnings. The instrument psychometrics was determined through an index of
      content validity (CVI) and internal consistency reliability. The instrument was
      determined to be valid (CVI = 3.75) and reliable (Cronbach's alpha = .971). The
      revised instrument was completed by a stratified, systematic random sample of 300
      parents of pediatric emergency patients. Participants rated the importance of
      each item for making the child feel cared for by nurses. Individual survey item
      means were computed. Items with the highest means represented the most important
      nurse caring behaviors. Leading nurse caring behaviors centered on carative
      factors of "human needs assistance" and "sensitivity to self and others." Nearly
      all nurse caring behaviors were important to the parents of pediatric patients,
      although some behaviors were not priority. It is important for nurses to provide
      family-centered care in a way that demonstrates nurse caring.

PMID- 23156210
TI  - [Natural history, epidemiology and statistics of gynecologic cancers].

PMID- 23156211
TI  - [Cancer prevention].

PMID- 23156212
TI  - [History and current status of gynecologic cancer treatment].

PMID- 23156213
TI  - [Registration of gynecologic malignancy in Japan].

PMID- 23156214
TI  - [Survival for gynecological cancer patients in Osaka, Japan].

PMID- 23156215
TI  - [Treatment guidelines in gynecologic malignancies].

PMID- 23156216
TI  - [Board certified gynecologic oncologist in Japan].

PMID- 23156217
TI  - [Cooperative researches for gynecologic cancers in Japan].

PMID- 23156219
TI  - [Translational research].

PMID- 23156218
TI  - [Current movement in global clinical trials--discussion at Gynecologic Cancer
      Intergroup (GCIG)].

PMID- 23156220
TI  - [Cervical cancer incidence: trends in Japan and world].

PMID- 23156221
TI  - [The natural history of cervical cancer: what's a risk factor?].

PMID- 23156222
TI  - [Mechanism of cervical carcinogenesis through expression of HPV oncoproteins].

PMID- 23156223
TI  - [Genetic abnormality in cervical cancer].

PMID- 23156224
TI  - [Analysis of clonality and HPV infection in benign, premalignant and malignant
      lesions of the uterine cervix].

PMID- 23156225
TI  - [Mechanism of metastasis in cervical cancer].

PMID- 23156226
TI  - [Pathology of carcinomas of uterine cervix].

PMID- 23156227
TI  - [Management of cervical intraepithelial neoplasia].

PMID- 23156228
TI  - [Adenoma malignum and lobular endocervical glandular hyperplasia (LEGH)].

PMID- 23156229
TI  - [New-concept: gastric-type adenocarcinoma of the uterine cervix].

PMID- 23156230
TI  - [Clinical staging and treatment of cervical cancer].

PMID- 23156231
TI  - [Pap smear and cervical cancer screening].

PMID- 23156232
TI  - [Cervical cancer screening using HPV DNA testing and cytology].

PMID- 23156233
TI  - [Genetic diagnosis: human papillomavirus (HPV) genotyping test].

PMID- 23156234
TI  - [Colposcopy].

PMID- 23156235
TI  - [Biopsy diagnosis of the cervical lesions].

PMID- 23156236
TI  - [Tumor marker, biomarker].

PMID- 23156237
TI  - [Imaging diagnosis of the uterine cervical carcinoma].

PMID- 23156238
TI  - [HPV (human papillomavirus) vaccine].

PMID- 23156239
TI  - [Development of new generation HPV vaccines: prophylactic and therapeutic].

PMID- 23156240
TI  - [Cervical cancer treatment: current perspective].

PMID- 23156241
TI  - [Surgical treatment for cervical cancer].

PMID- 23156242
TI  - [Conization].

PMID- 23156243
TI  - [Radical hysterectomy].

PMID- 23156244
TI  - [Modified radical hysterectomy].

PMID- 23156245
TI  - [Surgical treatment and function preservation in cervical cancer].

PMID- 23156246
TI  - [Total laparoscopic radical hysterectomy--port reduction technique].

PMID- 23156247
TI  - [Radical trachelectomy].

PMID- 23156248
TI  - [Para-aortic lymph node (PAN) dissection for patients with the uterine cervical
      cancer].

PMID- 23156249
TI  - [Current status of sentinel lymph node biopsy in cervical cancer].

PMID- 23156250
TI  - [The role of neoadjuvant chemotherapy for cervical cancer].

PMID- 23156251
TI  - [Adjuvant chemotherapy for cervical cancer].

PMID- 23156252
TI  - [Concurrent chemoradiotherapy (CCRT) in uterine cervical cancer].

PMID- 23156253
TI  - [Treatment of recurrent cervical cancer].

PMID- 23156254
TI  - [Treatment for adenocarcinoma and adenosquamous carcinoma of the uterine cervix].

PMID- 23156255
TI  - [Treatments of small cell carcinoma of uterine cervix].

PMID- 23156256
TI  - [Management and treatment for cervical cancer during pregnancy].

PMID- 23156257
TI  - [Incidence of cancer of corpus, the trend in Japan and the world].

PMID- 23156258
TI  - [Natural history and risk factors of endometrial carcinoma].

PMID- 23156259
TI  - [Hereditary endometrial cancer and genetic testing].

PMID- 23156260
TI  - [Effect of estrogen on molecular mechanisms of endometrial carcinogenesis].

PMID- 23156261
TI  - [Genetic alterations of endometrial carcinoma].

PMID- 23156262
TI  - [Biology of cancer stem cell in endometrial cancer].

PMID- 23156263
TI  - [Mechanism of metastasis in endometrial cancer].

PMID- 23156264
TI  - [Pathology and current topics on the selected histological types of endometrial
      carcinoma].

PMID- 23156265
TI  - [Precursors of the endometrial cancers].

PMID- 23156266
TI  - [Atypical polypoid adenomyoma (APAM)].

PMID- 23156267
TI  - [Clinical stage and therapy].

PMID- 23156268
TI  - [Endometrial cytology for endometrial cancer screening].

PMID- 23156269
TI  - [Ultrasound screening for endometrial carcinoma].

PMID- 23156270
TI  - [Hysteroscopy].

PMID- 23156271
TI  - [Histological diagnosis of endometrial cancer in biopsy specimen].

PMID- 23156272
TI  - [Genetic diagnosis of the endometrial cancer].

PMID- 23156273
TI  - [Clinical biomarkers of endometrial cancer].

PMID- 23156274
TI  - [Diagnostic imaging of the endometrial carcinoma].

PMID- 23156275
TI  - [A treatment strategy for endometrial cancer].

PMID- 23156276
TI  - [Hormonal treatment of endometrial cancer].

PMID- 23156277
TI  - [Introduction of the operative therapy].

PMID- 23156278
TI  - [Laparoscopic surgery].

PMID- 23156279
TI  - [Retroperitoneal lymphadenectomy in endometrial cancer].

PMID- 23156280
TI  - [Sentinel lymph node detection in endometrial cancer].

PMID- 23156281
TI  - [Role of chemotherapy in endometrial cancer].

PMID- 23156282
TI  - [Neoadjuvant chemotherapy for endometrial cancer].

PMID- 23156283
TI  - [Postoperative chemotherapy].

PMID- 23156284
TI  - [Radiotherapy].

PMID- 23156285
TI  - [Therapy of the recurrent endometrial cancer].

PMID- 23156286
TI  - [Management for serous adenocarcinoma and clear cell adenocarcinoma of the
      endometrium].

PMID- 23156287
TI  - [Uterine carcinosarcoma].

PMID- 23156288
TI  - [Diagnosis and treatment of endometrial stromal sarcoma].

PMID- 23156289
TI  - [Diagnosis and treatment of uterine leiomyosarcoma].

PMID- 23156290
TI  - [Epidemiological features of ovarian cancer in Japan and the world].

PMID- 23156291
TI  - [Natural history and risk factors of ovarian cancer development].

PMID- 23156292
TI  - [Clinical and genetic aspects of familial ovarian cancer].

PMID- 23156293
TI  - [Molecular genetic of ovarian cancer].

PMID- 23156294
TI  - [Genetic abnormalities in the pathogenesis of ovarian cancer].

PMID- 23156295
TI  - [Biological characteristics of ovarian cancer].

PMID- 23156296
TI  - [Malignant transformation of endometriosis].

PMID- 23156297
TI  - [Molecular mechanisms of peritoneal dissemination in ovarian cancer].

PMID- 23156298
TI  - [Metastasis related gene].

PMID- 23156299
TI  - [Immunological aspect of metastasis of ovarian cancer].

PMID- 23156300
TI  - [Pathology of ovarian cancer].

PMID- 23156301
TI  - [Precursors of ovarian carcinoma and epithelial borderline tumors: current topics
      in pathology].

PMID- 23156302
TI  - [Synchronous primary ovarian and endometrial carcinomas].

PMID- 23156303
TI  - [The general rules for clinical and pathological management of ovarian tumors
      part 1: histological classification and color atlas of ovarian tumors].

PMID- 23156304
TI  - [Staging for primary carcinoma of the ovary and treatment plan].

PMID- 23156305
TI  - [Ovarian cancer screening].

PMID- 23156306
TI  - [Clinical applications of ovarian cancer biomarkers].

PMID- 23156307
TI  - [Diagnostic imaging of ovarian cancer].

PMID- 23156308
TI  - [A practical approach to frozen-section diagnosis of ovarian tumors].

PMID- 23156309
TI  - [Treatment overview of ovarian cancer].

PMID- 23156310
TI  - [Overview of surgical treatment for ovarian cancer].

PMID- 23156311
TI  - [Basic operation for ovarian cancer].

PMID- 23156312
TI  - [Cytoreductive surgery in advanced epithelial ovarian cancer].

PMID- 23156313
TI  - [Strategies and techniques for resection of upper abdominal disease in patients
      with advanced ovarian cancer].

PMID- 23156314
TI  - [Pelvic and para-aortic lymphadenectomy].

PMID- 23156315
TI  - [Fertility-sparing surgery in epithelial ovarian cancer].

PMID- 23156316
TI  - [Chemotherapy for ovarian cancer].

PMID- 23156317
TI  - [Variation of primary chemotherapy for ovarian cancer].

PMID- 23156318
TI  - [Chemotherapy for recurrent ovarian cancer].

PMID- 23156319
TI  - [Intraperitoneal chemotherapy].

PMID- 23156320
TI  - [Neoadjuvant chemotherapy].

PMID- 23156321
TI  - [Molecular targeted therapies for epithelial ovarian cancer].

PMID- 23156322
TI  - [Treatment of recurrent ovarian cancer].

PMID- 23156323
TI  - [Treatment of clear cell adenocarcinoma and mucinous adenocarcinoma].

PMID- 23156324
TI  - [Malignant germ cell tumor--outline].

PMID- 23156325
TI  - [Operative treatment for the ovarian malignant germ tumor].

PMID- 23156326
TI  - [Chemotherapy for ovarian malignant germ cell tumors].

PMID- 23156327
TI  - [Current treatment strategy of sex cord--stromal tumors of the ovary by molecular
      targeted therapy].

PMID- 23156328
TI  - [Diagnosis and treatment for primary peritoneal cancer].

PMID- 23156329
TI  - [Clinical management of fallopian tube cancer].

PMID- 23156330
TI  - [Treatment for ovarian cancer during pregnancy].

PMID- 23156331
TI  - [New FIGO staging for vulvar cancer].

PMID- 23156332
TI  - [Vulvar cancer and vaginal cancer: precursor lesions and diagnoses].

PMID- 23156333
TI  - [Treatment of vulvar and vaginal cancer].

PMID- 23156334
TI  - [The general rules for clinical and pathological management of trophoblastic
      diseases--2011, the 3rd edition].

PMID- 23156335
TI  - [Recent changes in the incidence of gestational trophoblastic diseases in Japan].

PMID- 23156336
TI  - [Ultrasonographic findings of early-stage hydatidiform mole].

PMID- 23156337
TI  - [Pathologic diagnosis of hydatidiform mole].

PMID- 23156338
TI  - [Genetic diagnosis of hydatidiform mole].

PMID- 23156339
TI  - [Management of hydatidiform moles].

PMID- 23156340
TI  - [Diagnosis and management of invasive mole].

PMID- 23156341
TI  - [The diagnosis and treatment for choriocarcinoma].

PMID- 23156342
TI  - [A twin pregnancy with hydatidiform mole and coexisting fetus].

PMID- 23156343
TI  - [Diagnosis and treatment of placental site trophoblastic tumor].

PMID- 23156344
TI  - [Diagnosis and treatment of epithelioid trophoblastic tumor].

PMID- 23156345
TI  - [Recent advances in positron emission tomography (PET)].

PMID- 23156346
TI  - [Thromboprophylaxis in the therapy for gynecological cancer].

PMID- 23156347
TI  - [Robotic surgery in gynecological malignancies].

PMID- 23156348
TI  - [Complications of surgery for gynecologic cancer].

PMID- 23156349
TI  - [Palliative care of the patient with gynecologic cancer].

PMID- 23156350
TI  - [Supportive care in sexuality and cancer related infertility for gynecological
      cancer patients].

PMID- 23156351
TI  - [Prevention and treatment for postoperative lymphorrhea and chylous ascites in
      gynecologic malignancies].

PMID- 23156352
TI  - [Lower-limb lymphedema after surgery for gynecologic cancer].

PMID- 23156353
TI  - [Oral contraceptives as gynecological cancer prevention].

PMID- 23156354
TI  - [Hormone replacement therapy and cancer risk].

PMID- 23156355
TI  - [Application of assisted reproductive technology (ART) to patients with
      gynecologic malignancy].

PMID- 23156356
TI  - [Current status and the issues to be solved in Japanese children with diabetes
      mellitus].

PMID- 23156357
TI  - [Epidemiology of diabetes in children].

PMID- 23156358
TI  - [Diagnostic criteria for childhood diabetes mellitus].

PMID- 23156359
TI  - [Pathophysiology, diagnosis, and treatment of type 1 diabetes in children].

PMID- 23156360
TI  - [Pathophysiology, diagnosis and treatment of type 2 diabetes mellitus in children
      and adolescent].

PMID- 23156361
TI  - [The pathophysiology, diagnosis, and treatment for neonatal diabetes mellitus].

PMID- 23156362
TI  - [Prevention of pediatric diabetes].

PMID- 23156363
TI  - [Transition from pediatric to adult diabetes care systems].

PMID- 23156364
TI  - [Age-dependent alteration of energy and glucose metabolism].

PMID- 23156365
TI  - [Clinical characteristics in elderly patients with type 2 diabetes mellitus].

PMID- 23156366
TI  - [Current treatment and management of diabetes in elderly: introduction].

PMID- 23156367
TI  - [Oral hypoglycemic treatment for elderly diabetics].

PMID- 23156368
TI  - [Exercise and diet therapy for elderly patients with diabetes].

PMID- 23156369
TI  - [Practical use of comprehensive geriatric assessment in the care of older
      patients with diabetes mellitus].

PMID- 23156370
TI  - [Management of diabetic elderly with cognitive impairment].

PMID- 23156371
TI  - [Pathogenesis and concept of gestational diabetes mellitus].

PMID- 23156372
TI  - [Epidemiology of gestational diabetes mellitus].

PMID- 23156373
TI  - [Evidence-based medicine derived from HAPO study].

PMID- 23156374
TI  - [Usefulness and problems of diagnostic criteria for gestational diabetes
      mellitus].

PMID- 23156375
TI  - [Keynote of management and treatment for gestational diabetes mellitus].

PMID- 23156376
TI  - [Ways of preventing diabetes in mothers and children].

PMID- 23156377
TI  - [Follow-up of women with previous gestational diabetes mellitus].

PMID- 23156378
TI  - [Management of women with preexisting diabetes mellitus].

PMID- 23156379
TI  - [Treatment of hypertension in diabetic patients associated with hypertension].

PMID- 23156380
TI  - [Diabetes mellitus with dyslipidemia].

PMID- 23156381
TI  - [Diabetes with obesity].

PMID- 23156382
TI  - [Pathophysiology and therapeutic procedures for diabetes in Cushing syndrome].

PMID- 23156383
TI  - [Acromegaly].

PMID- 23156384
TI  - [Pheochromocytoma].

PMID- 23156385
TI  - [Glucagonoma].

PMID- 23156386
TI  - [Pancreatic diabetes].

PMID- 23156387
TI  - [Glucose intolerance in chronic liver disease].

PMID- 23156388
TI  - [Drug-induced diabetes mellitus].

PMID- 23156389
TI  - [Insulin autoimmune syndrome].

PMID- 23156390
TI  - [Lipoatrophic diabetes].

PMID- 23156391
TI  - [Insulin gene mutations].

PMID- 23156392
TI  - [Mutations in the insulin receptor gene].

PMID- 23156393
TI  - [Mitochondrial DNA mutation].

PMID- 23156394
TI  - [MODY(maturity onset diabetes of the young)].

PMID- 23156395
TI  - [Hereditary syndrome associated with diabetes mellitus].

PMID- 23156396
TI  - [The present situation and future problems on diabetic complications in Japan].

PMID- 23156397
TI  - [Genetic study for diabetic microvascular complications--recent advances and
      future perspectives].

PMID- 23156398
TI  - [Polyol-, hexosamine pathway and protein C kinase activation in the pathogenesis
      of diabetic complications].

PMID- 23156399
TI  - [Role of oxidative stress in pathogenesis of diabetic complications].

PMID- 23156400
TI  - [Endothelial dysfunction].

PMID- 23156401
TI  - [Role of advanced glycation end products (AGE) and soluble receptor for AGE
      (sRAGE) in vascular complications in diabetes].

PMID- 23156402
TI  - [Involvement of chronic inflammation in chronic diseases and diabetic
      complications].

PMID- 23156403
TI  - [Pathophysiological role of renin-angiotensin-aldosterone system in the
      development of diabetic complication].

PMID- 23156404
TI  - [Hypertension and abnormal lipid metabolism].

PMID- 23156405
TI  - [Therapeutic strategy in diabetes for the prevention of its complications].

PMID- 23156406
TI  - [Effect of glycemic control on development and progression of diabetic
      complication].

PMID- 23156407
TI  - [Treatment of hypertension].

PMID- 23156409
TI  - [Acute complications of diabetes].

PMID- 23156408
TI  - [Meaning of dyslipidemia management in diabetes].

PMID- 23156410
TI  - [Characteristics of diabetic macroangiopathy in Japan and East Asia].

PMID- 23156411
TI  - [Diabetes mellitus and cerebrovascular diseases].

PMID- 23156412
TI  - [Clinical aspects of diabetic coronary].

PMID- 23156413
TI  - [Diagnosis and treatment for peripheral arterial disease].

PMID- 23156414
TI  - [Epidemiology of diabetic retinopathy].

PMID- 23156415
TI  - [Large clinical studies on diabetic retinopathy].

PMID- 23156416
TI  - [Etiology of diabetic retinopathy].

PMID- 23156417
TI  - [Classification of diabetic retinopathy].

PMID- 23156418
TI  - [Pathophysiology and diagnosis of diabetic retinopathy].

PMID- 23156419
TI  - [Medical treatment for diabetic retinopathy].

PMID- 23156420
TI  - [Vitrectomy for the treatment of diabetic retinopathy].

PMID- 23156421
TI  - [Trends in drug development for diabetic retinopathy].

PMID- 23156422
TI  - [Other ocular complications related to diabetes mellitus].

PMID- 23156423
TI  - [Strategy for prevention from development and progression of diabetic
      retinopathy].

PMID- 23156424
TI  - [Epidemiology of diabetic nephropathy].

PMID- 23156425
TI  - [Pathogenesis of diabetic nephropathy: the role of inflammation].

PMID- 23156426
TI  - [Classification of diabetic nephropathy by Japanese Society of Nephrology and
      Japanse Diabetes Society and KDIGO CKD staging].

PMID- 23156427
TI  - [Pathology of diabetic nephropathy].

PMID- 23156428
TI  - [Pathogenesis and diagnosis of diabetic nephropathy].

PMID- 23156429
TI  - [Current therapy in diabetic patients with nephropathy].

PMID- 23156430
TI  - [Significance of RAAS inhibition in diabetic nephropathy].

PMID- 23156431
TI  - [iPS cell technology-based strategies for the treatment of diabetic nephropathy].

PMID- 23156432
TI  - [Registry system of diabetic nephropathy in Japan].

PMID- 23156433
TI  - [Epidemiology of diabetic neuropathy].

PMID- 23156434
TI  - [Pathogenesis of diabetic neuropathy].

PMID- 23156435
TI  - [Classification of diabetic neuropathy and clinical staging of diabetic
      polyneuropathy--current understanding].

PMID- 23156436
TI  - [Pathophysiology, neurological examinations and diagnosis of diabetic
      polyneuropathy].

PMID- 23156437
TI  - [Recent advances in treatment of diabetic polyneuropathy].

PMID- 23156438
TI  - [Clinical epidemiology of diabetic foot].

PMID- 23156439
TI  - [Pathogenesis of diabetic foot].

PMID- 23156440
TI  - [Preventive footcare for the occurrence and progress of the diabetic foot].

PMID- 23156441
TI  - [Management of diabetic-foot lesions from the view point of internal medicine].

PMID- 23156442
TI  - [Surgical treatment and topical wound management for diabetic foot].

PMID- 23156443
TI  - [Usefulness and problems of maggot therapy in Japan].

PMID- 23156444
TI  - [Regenerative medicine (cell therapy) for diabetic ulcer].

PMID- 23156445
TI  - [Periodontal disease].

PMID- 23156446
TI  - [Dementia in diabetes mellitus: preventive strategy].

PMID- 23156447
TI  - [Infectious disease associated with diabetes mellitus--mechanisms,
      classification, diagnosis and therapy].

PMID- 23156448
TI  - [Osteoporosis].

PMID- 23156449
TI  - [Sleep disorder, sleep disordered breathing].

PMID- 23156450
TI  - [Erectile dysfunction].

PMID- 23156451
TI  - [Diabetes mellitus and major depressive disorder].

PMID- 23156452
TI  - [NAFLD, NASH].

PMID- 23156453
TI  - [Chronic obstructive pulmonary disease (COPD)].

PMID- 23156454
TI  - [Revascularization for peripheral arterial disease in diabetic patients].

PMID- 23156455
TI  - [Systematic review of cancer risk in diabetes mellitus].

PMID- 23156456
TI  - [Diabetes and cancer risk: evidence from large-scale prospective study].

PMID- 23156457
TI  - [Insulin, IGF-I and cancer].

PMID- 23156458
TI  - [Relation between adiponectin/AdipoR and cancer in diabetes mellitus].

PMID- 23156459
TI  - [Diabetes and pancreatic cancer].

PMID- 23156460
TI  - [Impact of diabetes mellitus on hepatocellular carcinoma].

PMID- 23156461
TI  - [Diabetes and colorectal cancer].

PMID- 23156462
TI  - [Diabetes mellitus and the risk of gastric cancer].

PMID- 23156463
TI  - [Diabetes mellitus and prostate cancer].

PMID- 23156464
TI  - [Diabetes mellitus and women's cancer].

PMID- 23156465
TI  - [Management of patients with diabetes mellitus by using clinical path].

PMID- 23156466
TI  - [Medical relationship between the hospital and clinics about diabetic patients].

PMID- 23156467
TI  - [Improvement of quality of diabetes care with EHR and regional disease management
      mapping system].

PMID- 23156468
TI  - [American Association of Diabetes Educators, the current DSME (diabetes self
      management education) standards].

PMID- 23156469
TI  - [Insulin injection and patient education].

PMID- 23156470
TI  - [Clinical usefulness of educational admission in diabetes mellitus].

PMID- 23156471
TI  - [Psychoeducation on the people with diabetes--how do we support diabetic patients
      with psychological burden?].

PMID- 23156472
TI  - [Circadian rhythm and diabetes].

PMID- 23156473
TI  - [Hyperadiponectinemia and longevity].

PMID- 23156474
TI  - [Roles of sportology for the prevention of diabetes mellitus].

PMID- 23156475
TI  - [Current status and awaiting solution of training system of Board Certified
      Diabetologists of the Japan Diabetes Society].

PMID- 23156476
TI  - [Medical economy in the treatment of diabetes and its problems].

PMID- 23156477
TI  - [The pathophysiology, diagnosis, and treatment for neonatal hypoglycemia].

PMID- 23156478
TI  - [Hypoglycemia and cognitive impairment in diabetes mellitus].

PMID- 23156479
TI  - [Classification and mechanism of adverse drug reaction].

PMID- 23156480
TI  - [Factors affecting the occurrence of adverse drug reaction].

PMID- 23156481
TI  - [Pharmacogenomics for adverse drug reactions].

PMID- 23156482
TI  - [Diagnosis on adverse drug reactions].

PMID- 23156483
TI  - [Reporting system for adverse drug reactions and infections].

PMID- 23156484
TI  - [Classification criteria for severity of adverse drug reactions].

PMID- 23156485
TI  - [Precautions for use].

PMID- 23156486
TI  - [Relief system for adverse drug reactions].

PMID- 23156487
TI  - [Drug-induced liver injury].

PMID- 23156488
TI  - [Drug-induced nephropathy].

PMID- 23156489
TI  - [Drug induced hematological disorders].

PMID- 23156490
TI  - [Adverse effects of medicinal drugs to the skin].

PMID- 23156491
TI  - [Respiratory disorders].

PMID- 23156492
TI  - [Gastrointestinal disorder].

PMID- 23156493
TI  - [Drug-induced cardiotoxicity].

PMID- 23156494
TI  - [Psychotic disorder].

PMID- 23156495
TI  - [Neuromuscular side effects].

PMID- 23156496
TI  - [Drug-induced metabolic and endocrine disorders].

PMID- 23156497
TI  - [Fluid and electrolyte disturbances].

PMID- 23156499
TI  - [Adverse drug reactions of antiviral agents].

PMID- 23156498
TI  - [Antibiotics].

PMID- 23156500
TI  - [Myelosuppression].

PMID- 23156501
TI  - [Gastrointestinal complication of cancer chemotherapy].

PMID- 23156502
TI  - [Lung injury].

PMID- 23156503
TI  - [Skin toxicity, alopecia].

PMID- 23156504
TI  - [Glucocorticoid].

PMID- 23156505
TI  - [Nonsteroidal anti-inflammatory drugs].

PMID- 23156506
TI  - [Anti-rheumatic drugs].

PMID- 23156507
TI  - [Insulin preparation].

PMID- 23156508
TI  - [Adverse effects of insulin secretagogues (sulfonylureas and glinides)].

PMID- 23156509
TI  - [DPP-4 inhibitors and GLP-1 receptor agonists].

PMID- 23156510
TI  - [Biguanide, pioglitazone and alpha-glucosidase inhibitors].

PMID- 23156511
TI  - [Medicines for dyslipidemia].

PMID- 23156512
TI  - [Hormone replacement therapy].

PMID- 23156513
TI  - [Side-effects of therapeutic agents for osteoporosis].

PMID- 23156514
TI  - [Antithrombotic agents].

PMID- 23156515
TI  - [Adverse effects of cardiovascular agents in Japan--update 2012].

PMID- 23156516
TI  - [Calcium antagonists, diuretics, beta-blockers and alpha-blockers].

PMID- 23156517
TI  - [ACE inhibitor, ARB, renin inhibitor].

PMID- 23156518
TI  - [Side effects of bronchodilator and asthma medications].

PMID- 23156519
TI  - [Adverse effects of drugs for peptic ulcer diseases].

PMID- 23156520
TI  - [Medicines for liver diseases; interferon preparations and anti-hepatitis virus
      agents].

PMID- 23156521
TI  - [Adverse events of antipsychotics, antidepressants, mood stabilizers,
      antiepileptics, and psychostimulants].

PMID- 23156522
TI  - [Anxiolytics, hypnotics].

PMID- 23156523
TI  - [Anti-dementia drugs].

PMID- 23156524
TI  - [Side effects of Kampo extracts and patient compliance instruction].

PMID- 23156525
TI  - [Adverse events of vaccine].

PMID- 23156526
TI  - [Clinically important drug interactions].

PMID- 23156527
TI  - [Interactions of drug and nutrient].

PMID- 23156528
TI  - [Infants and children].

PMID- 23156529
TI  - [Drugs in pregnancy and lactation].

PMID- 23156530
TI  - [Adverse drug effects in elderly patients].

PMID- 23156531
TI  - [Management of adverse drug reaction on the patients with allergic diseases].

PMID- 23156532
TI  - [The case to the patient with renal insufficiency].

PMID- 23156533
TI  - [Anaphylaxis].

PMID- 23156534
TI  - [Angioedema].

PMID- 23156535
TI  - [Laryngeal edema].

PMID- 23156536
TI  - [Abnormality of liver functional test].

PMID- 23156537
TI  - [Drug-induced cholestasis].

PMID- 23156538
TI  - [Hepatitis].

PMID- 23156539
TI  - [Fulminant hepatitis].

PMID- 23156540
TI  - [Tubulointerstitial nephritis associated with drug reactions].

PMID- 23156541
TI  - [Acute kidney injury: AKI].

PMID- 23156542
TI  - [Drug-induced nephrotic syndrome].

PMID- 23156543
TI  - [Tumor lysis syndrome].

PMID- 23156544
TI  - [Urinary retention, voiding difficulty].

PMID- 23156545
TI  - [Hemorrhagic cystitis].

PMID- 23156546
TI  - [Aplastic anemia associated with drug].

PMID- 23156547
TI  - [Agranulocytosis (neutropenia)].

PMID- 23156548
TI  - [Thrombocytopenia].

PMID- 23156549
TI  - [Drug induced thrombotic thrombocytopenic purpura].

PMID- 23156550
TI  - [Heparin-induced thrombocytopenia (HIT)].

PMID- 23156551
TI  - [Thrombosis--adverse effect of drugs].

PMID- 23156552
TI  - [Coagulation disorder].

PMID- 23156553
TI  - [Disseminated intravascular coagulation (DIC)].

PMID- 23156555
TI  - [Drug and anemia].

PMID- 23156554
TI  - [Bleeding tendency].

PMID- 23156556
TI  - [Acute generalized exanthematous pustulosis].

PMID- 23156557
TI  - [Stevens-Johnson syndrome/toxic epidermal necrolysis].

PMID- 23156558
TI  - [Drug-induced hypersensitivity syndrome].

PMID- 23156559
TI  - [Drug-induced urticaria].

PMID- 23156560
TI  - [Contact dermatitis].

PMID- 23156561
TI  - [Hand-foot syndrome].

PMID- 23156562
TI  - [Drug-induced interstitial lung disease].

PMID- 23156563
TI  - [Acute eosinophilic pneumonia, eosinophilic pneumonia].

PMID- 23156564
TI  - [Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS)].

PMID- 23156565
TI  - [Drug-induced pleural diseases].

PMID- 23156566
TI  - [Respiratory depression].

PMID- 23156567
TI  - [Drug-induced pulmonary edema].

PMID- 23156568
TI  - [Drug-induced diffuse alveolar hemorrhage].

PMID- 23156569
TI  - [Aspirin-intolerant asthma].

PMID- 23156570
TI  - [Peptic ulcer (gastro-duodenal ulcer, acute gastric mucosal lesion, NSAIDs
      induced ulcer)].

PMID- 23156571
TI  - [Paralytic ileus].

PMID- 23156572
TI  - [Pseudomembranous colitis].

PMID- 23156573
TI  - [Severe diarrhea].

PMID- 23156575
TI  - [Stomatitis medicamentosa].

PMID- 23156574
TI  - [Drug-induced acute pancreatitis].

PMID- 23156576
TI  - [Congestive heart failure].

PMID- 23156577
TI  - [Ventricular tachycardia].

PMID- 23156578
TI  - [Drug-induced myocarditis and cardiomyopathy].

PMID- 23156579
TI  - [Arrhythmogenicity].

PMID- 23156580
TI  - [Drug dependence syndrome as a side effect of medical drug use].

PMID- 23156581
TI  - [Drug-induced abnormal behaviors].

PMID- 23156582
TI  - [Drug-induced depression].

PMID- 23156583
TI  - [Neuroleptic malignant syndrome (NMS)].

PMID- 23156584
TI  - [Serotonin syndrome].

PMID- 23156585
TI  - [Suicidal thinking and behavior].

PMID- 23156586
TI  - [Neonatal withdrawal syndrome or neonatal abstinence syndrome].

PMID- 23156587
TI  - [Ataxia].

PMID- 23156588
TI  - [Guillain-Barre syndrome].

PMID- 23156589
TI  - [Convulsions, epilepsy].

PMID- 23156590
TI  - [Dyskinesia].

PMID- 23156591
TI  - [Drug-induced leukoencephalopathy].

PMID- 23156592
TI  - [Drug induced peripheral neuropathy].

PMID- 23156593
TI  - [Drug induced parkinsonism].

PMID- 23156594
TI  - [Drug-induced aseptic meningitis].

PMID- 23156595
TI  - [Drug-related acute encephalopathy in childhood].

PMID- 23156596
TI  - [Rhabdomyolysis].

PMID- 23156597
TI  - [Malignant hyperthermia].

PMID- 23156598
TI  - [Visual disturbance].

PMID- 23156599
TI  - [Hearing loss].

PMID- 23156600
TI  - [Taste disorder].

PMID- 23156601
TI  - [Hypoglycemia].

PMID- 23156602
TI  - [Hyperglycemia].

PMID- 23156603
TI  - [SIADH].

PMID- 23156604
TI  - [Pseudoaldosteronism].

PMID- 23156605
TI  - [Hypothyroidism].

PMID- 23156606
TI  - [Drug induced thyrotoxicosis].

PMID- 23156607
TI  - [Drug-induced osteoporosis].

PMID- 23156608
TI  - [Bisphosphonate-related osteonecrosis of the jaws].

PMID- 23156609
TI  - [Idiopathic osteonecrosis of the femoral head].

PMID- 23156610
TI  - [Ovarian hyperstimulation syndrome].

PMID- 23156611
TI  - [Adverse events of molecular targeting drugs in oncology].

PMID- 23156612
TI  - [High-risk drugs].

PMID- 23156613
TI  - [Instruction of adverse drug reaction to patient].

PMID- 23156614
TI  - Preface to the special section on human factors and automation in vehicles:
      designing highly automated vehicles with the driver in mind.
AB  - OBJECTIVE: This special section brings together diverse research regarding driver
      interaction with advanced automotive technology to guide design of increasingly
      automated vehicles. BACKGROUND: Rapidly evolving vehicle automation will likely
      change cars and trucks more in the next 5 years than the preceding 50, radically
      redefining what it means to drive. METHOD: This special section includes 10
      articles from European and North American researchers reporting simulator and
      naturalistic driving studies. RESULTS: Little research has considered the
      consequences of fully automated driving, with most focusing on lane-keeping and
      speed control systems individually. The studies reveal two underlying design
      philosophies: automate driving versus support driving. Results of several
      studies, consistent with previous research in other domains, suggest that the
      automate philosophy can delay driver responses to incidents in which the driver
      has to intervene and take control from the automation. Understanding how to
      orchestrate the transfer or sharing of control between the system and the driver,
      particularly in critical incidents, emerges as a central challenge. CONCLUSION:
      Designers should not assume that automation can substitute seamlessly for a human
      driver, nor can they assume that the driver can safely accommodate the
      limitations of automation. Designers, policy makers, and researchers must give
      careful consideration to what role the person should have in highly automated
      vehicles and how to support the driver if the driver is to be responsible for
      vehicle control. As in other domains, driving safety increasingly depends on the
      combined performance of the human and automation, and successful designs will
      depend on recognizing and supporting the new roles of the driver.

PMID- 23156615
TI  - Heavy-truck drivers' following behavior with intervention of an integrated, in
      vehicle crash warning system: a field evaluation.
AB  - OBJECTIVE: This study is designed to evaluate heavy-truck drivers' following
      behavior and how a crash warning system influences their headway maintenance.
      BACKGROUND: Rear-end crashes are one of the major crash types involving heavy
      trucks and are more likely than other crash types to result in fatalities.
      Previous studies have observed positive effects of in-vehicle crash warning
      systems in passenger car drivers. Although heavy-truck drivers are generally more
      experienced, driver-related errors are still the leading factors contributing to
      heavy-truck-related rear-end crashes. METHOD: Data from a 10-month naturalistic
      driving study were used. Participants were 18 professional heavy-truck drivers
      who received warnings during the last 8 months of the study (treatment period)
      but not during the first 2 months (baseline period). Time headway and driver's
      brake reaction time were extracted and compared with condition variables,
      including one between-subjects variable (driver shift) and five within-subjects
      variables (treatment condition, roadway types, traffic density, wiper state, and
      trailer configuration). RESULTS: The presence of warnings resulted in a 0.28-s
      increase of mean time headway with dense on-road traffic and a 0.20-s increase
      with wipers on. Drivers also responded to the forward conflicts significantly
      faster (by 0.26 s, a 15% enhancement) in the treatment condition compared with
      responses in the baseline condition. CONCLUSION: Positive effects on heavy-truck
      drivers' following performance were observed with the warning system.
      APPLICATION: The installation of such in-vehicle crash warning systems can help
      heavy-truck drivers keep longer headway distances in challenging situations and
      respond quicker to potential traffic conflicts, therefore possibly increasing
      heavy-truck longitudinal driving safety.

PMID- 23156616
TI  - Driving with a partially autonomous forward collision warning system: how do
      drivers react?
AB  - OBJECTIVE: The effects of a forward collision warning (FCW) and braking system
      (FCW+) were examined in a driving simulator study analyzing driving and gaze
      behavior and the engagement in a secondary task. BACKGROUND: In-depth accident
      analyses indicate that a lack of appropriate expectations for possible critical
      situations and visual distraction may be the major causes of rear-end crashes.
      Studies with FCW systems have shown that a warning alone was not enough for a
      driver to be able to avoid the accident. Thus,an additional braking intervention
      by such systems could be necessary. METHOD: In a driving simulator experiment, 30
      drivers took part in a car-following scenario in an urban area. It was assumed
      that different lead car behaviors and environmental aspects would lead to
      different drivers' expectations of the future traffic situation. Driving with and
      without FCW+ was introduced as a between-subjects factor. RESULTS: Driving with
      FCW+ resulted in significantly fewer accidents in critical situations. This
      result was achieved by the system's earlier reaction time as compared with that
      of drivers. The analysis of the gaze behavior showed that driving with the system
      did not lead to a stronger involvement in secondary tasks. CONCLUSION: The study
      supports the hypotheses about the importance of missing expectations for the
      occurrence of accidents. These accidents can be prevented by an FCW+ that brakes
      autonomously. APPLICATION: The results indicate that an autonomous braking
      intervention should be implemented in FCW systems to increase the effectiveness
      of these assistance systems.

PMID- 23156617
TI  - Simulator training with a forward collision warning system: effects on driver
      system interactions and driver trust.
AB  - OBJECTIVE: The study addressed the role of familiarization on a driving simulator
      with a forward collision warning (FCW) and investigated its impact on driver
      behavior. BACKGROUND: Drivers need a good understanding of how an FCW system
      functions to trust it and use it properly. Theoretical and empirical data suggest
      that exploring the capacities and limitations of the FCW during the learning
      period improves operating knowledge and leads to increased driver trust in the
      system and better driver-system interactions.The authors tested this hypothesis
      by comparing groups of drivers differing in FCW familiarity. METHOD: During the
      familiarization phase, familiarized drivers were trained on the simulator using
      the FCW, unfamiliarized drivers simply read an FCW manual, and control drivers
      had no contact with the FCW. During the test, drivers drove the simulator and had
      to interact with traffic; both familiarized and unfamiliarized drivers used the
      FCW, whereas controls did not. RESULTS: Simulator familiarization improved driver
      understanding of FCW operation. Driver-system interactions were more effective:
      Familiarized drivers had no collisions, longer time headways, and better
      reactions in most situations. Familiarization increased trust in the FCW but did
      not raise system acceptance. CONCLUSION: Familiarization on the simulator had a
      positive effect on driver-system interactions and on trust in the system. The
      limitations of the familiarization method are discussed in relation to the
      driving simulator methodology. APPLICATION: Practicing on a driving simulator
      with driving-assistance systems could facilitate their use during real driving.

PMID- 23156618
TI  - Use patterns among early adopters of adaptive cruise control.
AB  - OBJECTIVE: The objective of this study was to investigate use patterns among
      early adopters of adaptive cruise control (ACC). BACKGROUND: Extended use ofACC
      may influence a driver's behavior in the long-term, which can have unintended
      safety consequences. METHOD: The authors examined the use of a motion-based
      simulator by 24 participants (15 males and 9 females). Cluster analysis was
      performed on drivers' use of ACC and was based on their gap settings, speed
      settings, number of warnings issued, and ACC disengaged. The data were then
      examined on the basis of driving performance measures and drivers' subjective
      responses to trust in ACC, understanding of system operations, and driving
      styles. Driving performance measures included minimum time headway, adjusted
      minimum time to collision, and drivers' reaction time to critical events.
      RESULTS: Three groups of drivers were observed on the basis of risky behavior,
      moderately risky behavior, and conservative behavior. Drivers in the conservative
      group stayed farther behind the lead vehicle than did drivers in the other two
      groups. Risky drivers responded later to critical events and had more ACC
      warnings issued. CONCLUSION: Safety consequences with ACC may be more prevalent
      in some driver groups than others. The findings suggest that these safety
      implications are related to trust in automation, driving styles, understanding of
      system operations, and personalities. APPLICATION: Potential applications of this
      research include enhanced design for next-generation ACC systems and
      countermeasures to improve safe driving with ACC.

PMID- 23156619
TI  - Fatigue and voluntary utilization of automation in simulated driving.
AB  - OBJECTIVE: A driving simulator was used to assess the impact on fatigue, stress,
      and workload of full vehicle automation that was initiated by the driver.
      BACKGROUND: Previous studies have shown that mandatory use of full automation
      induces a state of "passive fatigue" associated with loss of alertness. By
      contrast, voluntary use of automation may enhance the driver's perceptions of
      control and ability to manage fatigue. METHOD: Participants were assigned to one
      of two experimental conditions, automation optional (AO) and nonautomation (NA),
      and then performed a 35 min, monotonous simulated drive. In the last 5 min,
      automation was unavailable and drivers were required to respond to an emergency
      event. Subjective state and workload were evaluated before and after the drive.
      RESULTS: Making automation available to the driver failed to alleviate fatigue
      and stress states induced by driving in monotonous conditions. Drivers who were
      fatigued prior to the drive were more likely to choose to use automation, but
      automation use increased distress, especially in fatigue-prone drivers. Drivers
      in the AO condition were slower to initiate steering responses to the emergency
      event, suggesting optional automation may be distracting. CONCLUSION: Optional,
      driver-controlled automation appears to pose the same dangers to task engagement
      and alertness as externally initiated automation. APPLICATION: Drivers of
      automated vehicles may be vulnerable to fatigue that persists when normal vehicle
      control is restored. It is important to evaluate automated systems' impact on
      driver fatigue, to seek design solutions to the issue of maintaining driver
      engagement, and to address the vulnerabilities of fatigue-prone drivers.

PMID- 23156620
TI  - Control task substitution in semiautomated driving: does it matter what aspects
      are automated?
AB  - OBJECTIVE: The study was designed to show how driver attention to the road scene
      and engagement of a choice of secondary tasks are affected by the level of
      automation provided to assist or take over the basic task of vehicle control. It
      was also designed to investigate the difference between support in longitudinal
      control and support in lateral control. BACKGROUND: There is comparatively little
      literature on the implications of automation for drivers' engagement in the
      driving task and for their willingness to engage in non-driving-related
      activities. METHOD: A study was carried out on a high-level driving simulator in
      which drivers experienced three levels of automation: manual driving,
      semiautomated driving with either longitudinal or lateral control provided, and
      highly automated driving with both longitudinal and lateral control provided.
      Drivers were free to pay attention to the roadway and traffic or to engage in a
      range of entertainment and grooming tasks. RESULTS: Engagement in the nondriving
      tasks increased from manual to semiautomated driving and increased further with
      highly automated driving. There were substantial differences in attention to the
      road and traffic between the two types of semiautomated driving. CONCLUSION: The
      literature on automation and the various task analyses of driving do not
      currently help to explain the effects that were found. Lateral support and
      longitudinal support may be the same in terms of levels of automation but appear
      to be regarded rather differently by drivers.

PMID- 23156621
TI  - Highly automated driving, secondary task performance, and driver state.
AB  - OBJECTIVE: A driving simulator study compared the effect of changes in workload
      on performance in manual and highly automated driving. Changes in driver state
      were also observed by examining variations in blink patterns. BACKGROUND: With
      the addition of a greater number of advanced driver assistance systems in
      vehicles, the driver's role is likely to alter in the future from an operator in
      manual driving to a supervisor of highly automated cars. Understanding the
      implications of such advancements on drivers and road safety is important.
      METHOD: A total of 50 participants were recruited for this study and drove the
      simulator in both manual and highly automated mode. As well as comparing the
      effect of adjustments in driving-related workload on performance, the effect of a
      secondary Twenty Questions Task was also investigated. RESULTS: In the absence of
      the secondary task, drivers' response to critical incidents was similar in manual
      and highly automated driving conditions. The worst performance was observed when
      drivers were required to regain control of driving in the automated mode while
      distracted by the secondary task. Blink frequency patterns were more consistent
      for manual than automated driving but were generally suppressed during conditions
      of high workload. CONCLUSION: Highly automated driving did not have a deleterious
      effect on driver performance, when attention was not diverted to the distracting
      secondary task. APPLICATION: As the number of systems implemented in cars
      increases, an understanding of the implications of such automation on drivers'
      situation awareness, workload, and ability to remain engaged with the driving
      task is important.

PMID- 23156622
TI  - An adaptive driver support system: user experiences and driving performance in a
      simulator.
AB  - OBJECTIVE: The aim of this study was to test the implementation of an adaptive
      driver support system. BACKGROUND: Providing support might not always be
      desirable from a safety perspective, as support may lead to problems related to a
      human operator being out of the loop. In contrast, adaptive support systems are
      designed to keep the operator in the loop as much as possible by providing
      support only when necessary. METHOD: A total of 31 experienced drivers were
      exposed to three modes of lane-keeping support nonadaptive, adaptive, and no
      support. Support involved continuously updated lateral position feedback shown on
      a head-up display. When adaptive, support was triggered by performance-based
      indications of effort investment. Narrowing lane width and increasing density of
      oncoming traffic served to increase steering demand, and speed was fixed in all
      conditions to prevent any compensatory speed reactions. RESULTS: Participants
      preferred the adaptive support mode mainly as a warning signal and tended to
      ignore nonadaptive feedback. Furthermore, driving behavior was improved by
      adaptive support in that participants drove more centrally, displayed less
      lateral variation and drove less outside the lane's delineation when support was
      in the adaptive mode compared with both the no-support mode and the nonadaptive
      support mode. CONCLUSION: A human operator is likely to use machine-triggered
      adaptations as an indication that thresholds have been passed, regardless of the
      support that is initiated. Therefore supporting only the sensory processing stage
      of the human information processing system with adaptive automation may not
      feasible. APPLICATION: These conclusions are relevant for designing adaptive
      driver support systems.

PMID- 23156623
TI  - Sharing control with haptics: seamless driver support from manual to automatic
      control.
AB  - OBJECTIVE: Haptic shared control was investigated as a human-machine interface
      that can intuitively share control between drivers and an automatic controller
      for curve negotiation. BACKGROUND: As long as automation systems are not fully
      reliable, a role remains for the driver to be vigilant to the system and the
      environment to catch any automation errors. The conventional binary switches
      between supervisory and manual control has many known issues, and haptic shared
      control is a promising alternative. METHOD: A total of 42 respondents of varying
      age and driving experience participated in a driving experiment in a fixed-base
      simulator, in which curve negotiation behavior during shared control was compared
      to during manual control, as well as to three haptic tunings of an automatic
      controller without driver intervention. RESULTS: Under the experimental
      conditions studied, the main beneficial effect of haptic shared control compared
      to manual control was that less control activity (16% in steering wheel reversal
      rate, 15% in standard deviation of steering wheel angle) was needed for realizing
      an improved safety performance (e.g., 11% in peak lateral error). Full automation
      removed the need for any human control activity and improved safety performance
      (e.g., 35% in peak lateral error) but put the human in a supervisory position.
      CONCLUSION: Haptic shared control kept the driver in the loop, with enhanced
      performance at reduced control activity, mitigating the known issues that plague
      full automation. APPLICATION: Haptic support for vehicular control ultimately
      seeks to intuitively combine human intelligence and creativity with the benefits
      of automation systems.

PMID- 23156624
TI  - Trust in smart systems: sharing driving goals and giving information to increase
      trustworthiness and acceptability of smart systems in cars.
AB  - OBJECTIVE: We examine whether trust in smart systems is generated analogously to
      trust in humans and whether the automation level of smart systems affects
      trustworthiness and acceptability of those systems. BACKGROUND: Trust is an
      important factor when considering acceptability of automation technology. As
      shared goals lead to social trust, and intelligent machines tend to be treated
      like humans, the authors expected that shared driving goals would also lead to
      increased trustworthiness and acceptability of adaptive cruise control (ACC)
      systems. METHOD: In an experiment, participants (N = 57) were presented with
      descriptions of three ACCs with different automation levels that were described
      as systems that either shared their driving goals or did not. Trustworthiness and
      acceptability of all the ACCs were measured. RESULTS: ACCs sharing the driving
      goals of the user were more trustworthy and acceptable than were ACCs not sharing
      the driving goals of the user. Furthermore, ACCs that took over driving tasks
      while providing information were more trustworthy and acceptable than were ACCs
      that took over driving tasks without providing information. Trustworthiness
      mediated the effects of both driving goals and automation level on acceptability
      of ACCs. CONCLUSION: As when trusting other humans, trusting smart systems
      depends on those systems sharing the user's goals. Furthermore, based on their
      description, smart systems that take over tasks are judged more trustworthy and
      acceptable when they also provide information. APPLICATION: For optimal
      acceptability of smart systems, goals of the user should be shared by the smart
      systems, and smart systems should provide information to their user.

PMID- 23156625
TI  - Cusp catastrophe models for cognitive workload and fatigue in a verbally cued
      pictorial memory task.
AB  - OBJECTIVE: The aim of this study was to evaluate two cusp catastrophe models for
      cognitive workload and fatigue. They share similar cubic polynomial structures
      but derive from different underlying processes and contain variables that
      contribute to flexibility with respect to load and the ability to compensate for
      fatigue. BACKGROUND: Cognitive workload and fatigue both have a negative impact
      on performance and have been difficult to separate. Extended time on task can
      produce fatigue, but it can also produce a positive effect from learning or
      automaticity. METHOD: In this two-part experiment, 129 undergraduates performed
      tasks involving spelling, arithmetic, memory, and visual search. RESULTS: The
      fatigue cusp for the central memory task was supported with the quantity of work
      performed and performance on an episodic memory task acting as the control
      parameters. There was a strong linear effect, however. The load manipulations for
      the central task were competition with another participant for rewards, incentive
      conditions, and time pressure. Results supported the workload cusp in which trait
      anxiety and the incentive manipulation acted as the control parameters.
      CONCLUSION: The cusps are generally better than linear models for analyzing
      workload and fatigue phenomena; practice effects can override fatigue. Future
      research should investigate multitasking and task sequencing issues, physical
      cognitive task combinations, and a broader range of variables that contribute to
      flexibility with respect to load or compensate for fatigue. APPLICATIONS: The new
      experimental medium and analytic strategy can be generalized to virtually any
      real-world cognitively demanding tasks. The particular results are generalizable
      to tasks involving visual search.

PMID- 23156626
TI  - The impact of intonation and valence on objective and subjective attention
      capture by auditory alarms.
AB  - OBJECTIVE: The objective was to study the involuntary capture of attention by
      spoken words varying in intonation and valence. BACKGROUND: In studies of verbal
      alarms, the propensity of alarms to capture attention has been primarily assessed
      with the use of subjective ratings of their perceived urgency. Past studies
      suggest that such ratings vary with the alarms' spoken urgency and content.
      METHOD: We measured attention capture by spoken words varying in valence
      (negative vs. neutral) and intonation (urgently vs. nonurgently spoken) through
      subjective ratings and behavioral measures. The key behavioral measure was the
      response latency to visual stimuli in the presence of spoken words breaking away
      from the periodical repetition of a tone. RESULTS: The results showed that all
      words captured attention relative to a baseline standard tone but that this
      effect was partly counteracted by a relative speeding of responses for urgently
      compared with nonurgently spoken words. Word valence did not affect behavioral
      performance. Rating data showed that both intonation and valence increased
      significantly perceived urgency and attention grabbing without any interaction.
      CONCLUSION: The data suggest a congruency between subjective ratings and
      behavioral performance with respect to spoken intonation but not valence.
      APPLICATION: This study demonstrates the usefulness and feasibility of objective
      measures of attention capture to help design efficient alarm systems.

PMID- 23156627
TI  - The effect of SPAM administration during a dynamic simulation.
AB  - OBJECTIVE: The objective of this study was to determine whether administration of
      the situation present assessment method (SPAM) affects workload and/or task
      performance. BACKGROUND: SPAM probes are thought to isolate workload from the
      assessment of situation awareness (SA) by including a warning signal before
      asking an SA-related question. However, there is a good reason to think that SPAM
      may still have an effect on dynamic workload and task performance. Specifically,
      nearly all dual tasks affect workload and performance; thus, it would be
      surprising if SPAM did not. METHOD: Following the methods of Durso, Bleckley, and
      Dattel, I evaluated workload and performance on the Air Traffic Scenarios Test in
      SPAM, non-SPAM probe, and no-probe conditions. RESULTS: Global workload was
      unaffected by probe administration. However, at least with novice performers,
      SPAM probes affected task performance. CONCLUSION: The use of a warning signal
      does not eliminate performance decrements associated with secondary tasks.
      Moreover, there may be performance decrements unique to SPAM. APPLICATION:
      Cautious users of online assessment measures, such as SPAM, may want to remove
      performance immediately subsequent to probes from analysis, use an interprobe
      interval longer than 2.83 min, and construct their assessment measures to reduce
      display search times unrelated to primary task performance.

PMID- 23156628
TI  - U.S. truck driver anthropometric study and multivariate anthropometric models for
      cab designs.
AB  - OBJECTIVE: This study presents data from a large-scale anthropometric study of
      U.S. truck drivers and the multivariate anthropometric models developed for the
      design of next-generation truck cabs. BACKGROUND: Up-to-date anthropometric
      information of the U.S. truck driver population is needed for the design of safe
      and ergonomically efficient truck cabs. METHOD: We collected 35 anthropometric
      dimensions for 1,950 truck drivers (1,779 males and 171 females) across the
      continental United States using a sampling plan designed to capture the
      appropriate ethnic, gender, and age distributions of the truck driver population.
      RESULTS: Truck drivers are heavier than the U.S.general population, with a
      difference in mean body weight of 13.5 kg for males and 15.4 kg for females. They
      are also different in physique from the U.S. general population. In addition, the
      current truck drivers are heavier and different in physique compared to their
      counterparts of 25 to 30 years ago. CONCLUSION: The data obtained in this study
      provide more accurate anthropometric information for cab designs than do the
      current U.S. general population data or truck driver data collected 25 to 30
      years ago. Multivariate anthropometric models, spanning 95% of the current truck
      driver population on the basis of a set of 12 anthropometric measurements, have
      been developed to facilitate future cab designs. APPLICATION: The up-to-date
      truck driver anthropometric data and multivariate anthropometric models will
      benefit the design of future truck cabs which, in turn, will help promote the
      safety and health of the U.S. truck drivers.

PMID- 23156629
TI  - Aesthetics: Honoring the team approach.

PMID- 23156630
TI  - The impact of effective online marketing.

PMID- 23156631
TI  - Predictable stabilization of the lower denture: comment and reply.

PMID- 23156632
TI  - Xerostomia: etiology, diagnosis, and management.

PMID- 23156633
TI  - Exploring minimally invasive options: managing demands, expectations, and
      outcomes.

PMID- 23156634
TI  - A simple and effective treatment for white spots.

PMID- 23156635
TI  - The new age of ethical cosmetic dentistry: implementing the concept of
      progressive smile design.

PMID- 23156636
TI  - How do masters do it?

PMID- 23156637
TI  - The CT/CBCT-based team approach to care: Part 2: communication with the surgeon
      to support the final prosthesis.

PMID- 23156638
TI  - Place and restore dental implants economically.

PMID- 23156639
TI  - Direct composite resins continue to evolve.

PMID- 23156640
TI  - Utilizing bioactive liners. Stimulating post-traumatic dentin formation.

PMID- 23156641
TI  - Flexible partial denture variations. The use of circumferential, combination, and
      continuous clasp designs.
AB  - The new design potential of the flexible partial and its clasp allows for a new
      treatment approach to the well-established problems of retention, stability, and
      strength. The 4 main clasp designs include the conventional, the circumferential,
      the combination, and the continuous clasp. The proper use of these various
      designs can be a strong foundation upon which to develop the clinical strengths
      of the flexible partial denture.

PMID- 23156642
TI  - Repair technique for broken cast teeth.

PMID- 23156643
TI  - Misplaced hope: misleading health service practitioner representations and
      consumer protection.
AB  - A series of court and tribunal decisions in the course of 2012 in Australia has
      highlighted the vulnerability of seriously ill patients to overtures and
      advertising by charismatic health practitioners offering panaceas of unproven
      efficacy. Drawing upon the findings of the Victorian Court of Appeal in relation
      to Noel Campbell, the Deputy State Coroner of Western Australia in relation to
      Helfried Sartori, and the Victorian Civil and Administrative Tribunal in relation
      to Reza Ghaffurian, it is argued that there is a strong public interest in the
      capacity for effective early intervention by government in relation to
      unscrupulous and unethical conduct by health practitioners, whether they are
      registered or unregistered. For Australia a constructive reform would be
      nationally consistent legislation to regulate unregistered health practitioners.

PMID- 23156644
TI  - Legal capacity under the Convention on the Rights of Persons with Disabilities.
AB  - Article 12 of the United Nations Convention on the Rights of Persons with
      Disabilities requires states parties to ensure that persons with disabilities
      "enjoy legal capacity on an equal basis with others in all aspects of life". This
      column explores what is meant by "legal capacity" and its constituent elements of
      legal standing and legal agency. It outlines recent research on what is meant by
      "support" to exercise legal capacity and explores the issue of whether mental
      health and guardianship laws that enable substituted decision-making for those
      with mental and intellectual impairments contravene Article 12.

PMID- 23156645
TI  - A new ball game: the United Nations Convention on the Rights of Persons with
      Disabilities and assumptions in care for people with dementia.
AB  - The United Nations Convention on the Rights of Persons with Disabilities is a
      powerful international instrument which imposes significant responsibilities on
      signatories. This column discusses changes in the definition of legal capacity
      which will have significant impacts on decision-making related to people with
      dementia. Various restrictions and limitations on personal freedoms are discussed
      in light of the Convention. The main focus is on challenges to existing paradigms
      of substitute decision-making, which are in wide use through a guardianship
      model. Under Art 12 of the Convention, moves to supported decision-making will
      result in significant changes in ensuring the rights of people with dementia.
      There are challenges ahead in implementing supported decision-making schemes, not
      only due to tension with existing practices and legislation, but also the
      difficulty of developing and resourcing workable schemes. This is particularly so
      with advanced dementia, which is acknowledged as a pressing issue for Australia
      due to effective health care, an ageing population and changing expectations.

PMID- 23156646
TI  - A fair dinkum duty of open disclosure following medical error.
AB  - Supporting patients and families in circumstances where medical error has caused
      significant harm is said to be governed by the principles of ordinary treatment:
      honest, open communication, empathy and respect. By and large, harmed patients
      look for acknowledgment of the events that occurred including errors, acceptance
      of responsibility, a sincere apology, and assurance that lessons learned will be
      put to preventive use. Australia's National Open Disclosure Standard purports to
      respond to these reasonable expectations, yet it advises health care
      professionals that while they may express regret for what has occurred, they
      should take care not to state or agree that they, or other health care
      professionals, or health care organisations, are liable for the harm caused to
      the patient. The National Open Disclosure Standard is currently being reviewed,
      and the Consultation Draft of the Australian Open Disclosure Framework appears to
      move things closer to its stated finding that ethical practice prioritises
      organisational and individual learning from error, rather than an organisational
      risk-management approach. However, it remains the case that the sense of apology
      in the Consultation Draft is one of stating regret, not of accepting
      responsibility This dissonance in the Draft Framework wording may represent a
      continuing disingenuousness on the part of health professionals and their
      institutions regarding the kind of apologies that patients look for. Following
      Berlinger, the current author argues that expressions of regret are not
      apologies, since an apology presupposes the fault that health professionals are
      advised they avoid admitting. But honest, open communication surely implies both
      materially relevant disclosure, which would include acknowledgment of fault where
      that is known, and a genuine apology, as part of the continuing doctor-patient
      relationship. To the extent that open disclosure policies and practices fudge
      complete disclosure, admission of fault and genuine apology, they remain
      deficient instruments in the respect and beneficence owed patients harmed by
      health care. Advice to health care professionals to not admit fault, and
      implicitly to not apologise genuinely, are motivated by legal liability
      considerations. There is strong evidence that comprehensive communication,
      including genuine apology and consistent with the medical ethical principle of
      veracity, is associated with reduced levels of litigation. State health
      department Open Disclosure policies and State and Territory civil liability
      legislation should be reviewed to remove obfuscatory and dissembling language and
      increase consistency between jurisdictions and between policies and statutes. The
      National Open Disclosure Standard should be revised to encourage and support full
      disclosure and genuine apology. If these processes fail, statutory reform should
      be considered.

PMID- 23156647
TI  - Civil liberties and the critics of safe vaccination: Australian Vaccination
      Network Inc v Health Care Complaints Commission [2012] NSWSC 110.
AB  - Public immunisation programs have, time and again, demonstrated their
      effectiveness at reducing mortality and morbidity from vaccine-preventable
      diseases such as measles and pertussis. Governments, health agencies and almost
      all health practitioners regard vaccines as safe and cost-effective treatments
      with a low risk profile. Nevertheless, despite, or perhaps because of, their
      success, immunisation programs and vaccines have increasingly been questioned by
      various lobby groups, sceptical of the safety of vaccines and the motives of
      those who administer them. Whereas the reach of these groups would have once been
      limited by the cost of postage, the internet has delivered a global audience. The
      extent to which these anti-vaccination advocates are expected to comply with the
      ethical and professional standards applied to registered health professionals
      remains unresolved in Australia. As demonstrated in the case of Australian
      Vaccination Network Inc v Health Care Complaints Commission [2012] NSWSC 110, the
      ability of professional oversight bodies to regulate the information promoted by
      these lobby groups is limited by traditional conceptions of the doctor-patient
      relationship and the clinical setting in which medical advice is delivered.
      Acknowledging that vaccines, like all medical treatments, involve some level of
      risk, this article explores the relationship between the state, parents, family,
      medical professionals and such lobbyists within a human rights framework,
      suggesting that most public immunisation programs deliver benefits in "the best
      interest of the child" that, on balance, provide a good result for the civil
      liberties of Australians.

PMID- 23156648
TI  - Levelling the playing field? Sharing of influenza viruses and access to vaccines
      and other benefits.
AB  - With the adoption of the Pandemic Influenza Preparedness Framework, including its
      annexes, by the 64th World Health Assembly, this article investigates the
      disproportionate burden of risk and benefits between resource-poor countries in
      the developing South and resource-rich industrialised developed nations of the
      North in the World Health Organisation's Standard Material Transfer Agreement
      (SMTA) for accessing and sharing influenza viruses. It concludes that the
      countries of the South have a unique opportunity to level the playing field
      through providing timely and affordable access to life-saving vaccine and
      meaningful benefit-sharing that will deliver technology and economic development.
      Importantly, the article also demonstrates that SMTAs are not merely a
      redirection of existing resources from North to South but offer a solution to the
      ongoing shortage of pandemic influenza vaccine by enabling the South to access
      technology necessary for sustainable vaccine production and thus increasing
      global vaccine capacity.

PMID- 23156649
TI  - The dollars and sense of restraints and seclusion.
AB  - Restraints and seclusion are a common practice in many human service settings
      despite the increasing evidence questioning their efficacy and appropriateness.
      There are many detrimental effects on people subject to these practices, such as
      falls, injury, psychological trauma and even death. In addition to the impact on
      people being served, there is also a range of negative effects on organisations
      and the workforce. This article outlines and discusses the costs to organisations
      in implementing restraints and seclusion, and the economic cost-benefits to be
      gained in working towards the safe elimination of restraints and seclusion. A
      brief outline of ethical alternatives to restraints and seclusion is explored.
      The emerging research evidence suggests that it is possible to achieve the safe
      elimination of restraints and seclusion in a human service organisation.

PMID- 23156650
TI  - Are people who claim compensation "cured by a verdict"? A longitudinal study of
      health outcomes after whiplash.
AB  - This study examines whether the lure of injury compensation prompts whiplash
      claimants to overstate their symptoms. Claim settlement is the intervention of
      interest, as it represents the point at which there is no further incentive to
      exaggerate symptoms, and neck pain at 24 months is the outcome of interest.
      Longitudinal data on neck pain scores and timing of claim settlement were
      regressed, controlling for the effect of time on recovery, to compare outcomes in
      claimants who had and had not settled their compensation claims. The results show
      clearly that removing the financial incentive to over-report symptoms has no
      effect on self-reported neck pain in a fault-based compensation scheme, and this
      finding concurs with other studies on this topic. Policy decisions to limit
      compensation in the belief that claimants systematically misrepresent their
      health status are not supported empirically Claimants do not appear to be "cured
      by a verdict".

PMID- 23156651
TI  - Criticisms of African trials fail to withstand scrutiny: male circumcision does
      prevent HIV infection.
AB  - A recent article in the JLM (Boyle GJ and Hill G, "Sub-Saharan African Randomised
      Clinical Trials into Male Circumcision and HIV Transmission: Methodological,
      Ethical and Legal Concerns" (2011) 19 JLM 316) criticises the large randomised
      controlled trials (RCTs) that scientists, clinicians and policy-makers worldwide
      have concluded provide compelling evidence in support of voluntary medical male
      circumcision (VMMC) as an effective HIV prevention strategy. The present article
      addresses the claims advanced by Boyle and Hill, demonstrating their reliance on
      outmoded evidence, outlier studies, and flawed statistical analyses. In the
      current authors' view, their claims portray misunderstandings of the design,
      execution and interpretation of findings from RCTs in general and of the
      epidemiology of HIV transmission in sub-Saharan Africa in particular. At the same
      time they ignore systematic reviews and meta-analyses using all available data
      arising from good-quality research studies, including RCTs. Denial of the
      evidence supporting lack of male circumcision as a major determinant of HIV
      epidemic patterns in sub-Saharan Africa is unsubstantiated and risks undermining
      the evidence-based, large-scale roll-out of VMMC for HIV prevention currently
      underway. The present article highlights the quality, consistency and robustness
      of the scientific evidence that underpins the public health recommendations,
      guidance, and tools on VMMC. Millions of HIV infections will be averted in the
      coming decades as VMMC services scale-up to meet demand, providing direct
      benefits for heterosexual men and indirect benefits for their female partners.

PMID- 23156652
TI  - Childhood obesity, parental duties of care and strategies for intervention.
AB  - Childhood obesity is an increasingly serious issue which causes significant
      health problems among children. There are numerous causes of childhood obesity.
      However, the ultimate responsibility for the problems and costs associated with
      an obese child should be attributed to that child's parents. Parents owe a duty
      of care to their child and, when their child is obese, have arguably breached
      that duty. However, if parents were required to pay their child damages, this
      would arguably be problematic and of little utility. Rather, intervention
      strategies should be implemented which seek to treat and prevent childhood
      obesity and to address the identified causes of childhood obesity.

PMID- 23156653
TI  - Reappraising consent: conducting ethical psychiatric research in Singapore.
AB  - Singapore is legally restrictive when it comes to research involving minors. The
      age of majority is 21 and parental consent is required for participation in
      medical research. This article explores the age of majority and the issues
      related to obtaining consent for research in Singapore, focusing on "young
      adults" (17-21 years), using an example of a translational and clinical research
      project called the Longitudinal Youth at Risk Study (LYRIKS). It describes the
      unique legal and social conditions pertaining to the age of majority in
      Singapore, before presenting an argument for consideration as to whether the age
      of consent to participate in research should be reviewed. It concludes that
      rather than a set of doctrinaire rules for the age of participation in research,
      there should be an assessment of the kind of tasks that minors can assume
      themselves in respect to a specific project, and the degree of parental
      involvement.

PMID- 23156654
TI  - The regulation of preimplantation genetic diagnosis: is there anything the United
      Kingdom can learn from the Australian experience?
AB  - The United Kingdom fertility regulator, the Human Fertilisation and Embryology
      Authority (HFEA), is set to be abolished and its functions transferred to the
      Care Quality Commission. Together with the Human Fertilisation and Embryology Act
      1990 (UK), the HFEA has played a central role in the regulation of
      preimplantation genetic diagnosis (PGD) and human leukocyte antigen tissue typing
      (HLA typing). Australia, on the other hand, does not have a national regulatory
      body for assisted reproductive technologies, which are instead regulated by a
      series of national guidelines, State legislation and State regulators. Using PGD
      and HLA typing as a focal point, this article asks, is there anything the United
      Kingdom can learn from Australia?

PMID- 23156655
TI  - The legal status of the fetus in New South Wales.
AB  - The issue of how to define the legal status of the fetus is complex. Three
      clinical cases with fetal losses following motor vehicle accidents raise
      important issues regarding the legal status of the unborn child. Legislation was
      submitted to the New South Wales Parliament in the form of the Crimes Amendment
      (Grievous Bodily Harm) Bill 2005 (NSW) but was subsequently repealed. Medical
      technological advances make the viability of a fetus a shifting standard and
      encourage the comparison between newborns and late-term fetuses, offer increased
      fetal health status information and provide greater capacity to maintain the life
      of babies born prematurely. In view of the sophisticated state of medical care
      available in New South Wales, the three cases reviewed highlight the discrepancy
      between the medical recognition of the fetus as a patient and its lack of legal
      recognition.

PMID- 23156656
TI  - Avoiding a fate worse than death: an argument for legalising voluntary physician
      based euthanasia.
AB  - The legalisation of voluntary physician-based euthanasia is currently the subject
      of much political, social and ethical debate and there is evidence in Australia
      of growing support for its implementation. In addressing many of the issues that
      surround legalisation, the article looks at some overseas jurisdictions that have
      legalised euthanasia to determine whether the social, political and ethical
      concerns prominent in the Australian debate have proved problematic in other
      jurisdictions. In addition, the article examines the report on the Dying with
      Dignity Bill 2009 (Tas) which commented extensively on the issues relating to
      voluntary physician-based euthanasia.

PMID- 23156657
TI  - The many cases of XFJ: suitable to drive a taxi or "killer cabbie"?
AB  - For 10 years, the refugee now known by the pseudonym XFJ attempted to gain
      accreditation to drive a taxi-cab. After many internal reviews and rejections by
      the Victorian Taxi Directorate, XFJ appealed to the Victorian Civil and
      Administrative Tribunal (VCAT). The difficulty for XFJ was that shortly after
      arriving in Australia, he had killed his estranged wife. The Supreme Court of
      Victoria subsequently found him not guilty of murder on the grounds of insanity.
      Since XFJ's mental health has been stable for many years, much of the legal
      argument at VCAT and the court cases that followed centred around whether he was
      "suitable in other respects to provide the service" of driving a taxi, as
      required by s 169(1)(b)(ii) of the Transport Act 1983 (Vic). This article looks
      at the tension between the expert medical evidence and the concept of "suitable
      in other respects" which XFJ's opponents claimed included the maintenance of
      public confidence and the meeting of community expectations.

PMID- 23156658
TI  - The economics of medical technology.

PMID- 23156659
TI  - Aspects of research and development contract terms in the bio/pharmaceutical
      sector.
AB  - PURPOSE: The cost of new drug development is increasing every year.
      Pharmaceutical companies use R&D joint ventures, mergers, and outsource different
      stages of pharmaceutical R&D activities for a faster and cost minimizing method
      of innovation. Pharmaceutical companies outsource R&D activities to independent
      small biotech or pharmaceutical companies that specialize in different stages of
      pharmaceutical R&D. This chapter examines the determinants of the payment
      structure of research contracts between large bio/pharmaceutical companies and
      specialized research firms. METHODS: Determinants of R&D contracts are analyzed
      using detailed R&D contract data between bio/pharmaceutical companies and
      independent research firms for 10 years. A multinomial logit model is used in
      order to understand the determinants of three different types of contracts;
      royalty contracts, fixed payment contracts, and the mixed contracts. FINDINGS:
      Under uncertainty, the likelihood of a royalty contract rises for the early
      stages of the research and with the patent stock of the research firm. It is more
      likely to observe both royalty and fixed payment if the pharmaceutical client has
      past contracts with the same research firm. The results also suggest that if Food
      and Drug Administration (FDA) is more stringent in any disease area in reviewing
      the new drug application, then the likelihood of signing pure royalty contract
      decreases. IMPLICATIONS: Understanding the nature of R&D contracts and the
      effects of FDA's behavior on the pharmaceutical R&D contract is important because
      these contracts not only affect the cost of new drug invention but also the
      quality and the rate of invention. VALUE: Results are useful for both the
      pharmaceutical companies and the economic/business researchers.

PMID- 23156660
TI  - Effects of regulation on drug launch and pricing in interdependent markets.
AB  - PURPOSE: This study examines the effect of price regulation and competition on
      launch timing and pricing of new drugs. METHODS: Our data cover launch experience
      in 15 countries from 1992 to 2003 for drugs in 12 major therapeutic classes. We
      estimate a two-equation model of launch hazard and launch price of new drugs.
      FINDINGS: We find that launch timing and prices of new drugs are related to a
      country's average prices of established products in a class. Thus to the extent
      that price regulation reduces price levels, such regulation directly contributes
      to launch delay in the regulating country. Regulation by external referencing,
      whereby high-price countries reference low-price countries, also has indirect or
      spillover effects, contributing to launch delay and higher launch prices in low
      price referenced countries. IMPLICATIONS: Referencing policies adopted in high
      price countries indirectly impose welfare loss on low-price countries. These
      findings have implications for US proposals to constrain pharmaceutical prices
      through external referencing and drug importation.

PMID- 23156661
TI  - The effect of pharmaceutical innovation on the functional limitations of elderly
      americans: evidence from the 2004 National Nursing Home Survey.
AB  - PURPOSE: To examine the effect of pharmaceutical innovation on the functional
      status of nursing home residents. METHODOLOGY/APPROACH: Estimation of econometric
      models of the ability of nursing home residents to perform activities of daily
      living (ADLs) using cross-sectional, patient-level data from the 2004 National
      Nursing Home Survey. The explanatory variables of primary interest are the
      characteristics (e.g., the mean vintage (FDA approval year)) of the medications
      used by the resident. We control for age, sex, race, marital status, veteran
      status, where the resident lived prior to admission, primary diagnosis at the
      time of admission, up to 16 diagnoses at the time of the interview, sources of
      payment, and facility fixed effects. FINDINGS: The ability of nursing home
      residents to perform ADLs is positively related to the number of "new" (post
      1990) medications they consume, but unrelated to the number of old medications
      they consume. I estimate that if 2004 nursing home residents had used only old
      medications, the fraction of residents with all five ADL dependencies (number of
      activities for which the resident is not independent) would have been 58% instead
      of 50%. SOCIAL IMPLICATIONS: During 1990-2004, pharmaceutical innovation for
      reduced the functional limitations of nursing home residents by between and 1.2%
      and 2.1% per year. ORIGINALITY/VALUE OF CHAPTER: The first public-use survey of
      nursing homes that contains detailed information about medication use, and better
      data on functional status than previous surveys, is used to help explain why
      there has been a significant decline in the functional limitations of older
      people.

PMID- 23156662
TI  - Comparative effectiveness research, technological abandonment, and health care
      spending.
AB  - PURPOSE: Policymakers hope that comparative effectiveness research will identify
      examples of widely used therapies that are no better than less expensive
      alternatives and, consequently, reduce health care spending. Comparative
      effectiveness research is unlikely to reduce spending if physicians are quick to
      adopt effective treatments but slow to abandon ineffective ones.
      METHODOLOGY/APPROACH: We present a theoretical model that shows how physicians
      will adopt new treatments in response to positive evidence more readily than they
      abandon existing treatments in response to negative evidence if the marginal
      costs of production decline post-adoption. We report trends in the use of two
      common procedures, percutaneous coronary intervention (PCI) for patients with
      stable angina and routine episiotomy in vaginal childbirth, where comparative
      effectiveness research studies have failed to find evidence of a benefit.
      FINDINGS: Use of PCI and episiotomy have declined over time but are still
      excessive based on the standards implied by comparative effectiveness research.
      PRACTICAL IMPLICATIONS (IF APPLICABLE): The findings suggest that comparative
      effectiveness research has the potential to reduce costs but additional efforts
      are necessary to fully realize savings from abandonment. ORIGINALITY/VALUE OF
      CHAPTER: There is a large literature on technological adoption in health care,
      but few studies address technological abandonment. Understanding abandonment is
      important for efforts to decrease health care costs by reducing use of
      ineffective but costly treatments.

PMID- 23156663
TI  - How do initial signals of quality influence the diffusion of new medical
      products? The case of new cancer drug treatments.
AB  - PURPOSE: Objective measures of a new treatment's expected ability to improve
      patients' health are presumed to be significant factors influencing physicians'
      treatment decisions. Physicians' behavior may also be influenced by their
      patients' disease severity and insurance reimbursement policies, firm promotional
      activities and public media reports. This chapter examines how objective evidence
      of the incremental effectiveness of novel drugs to treat cancer
      ("chemotherapies") impacts the rate at which physicians' adopt these treatments
      into practice, holding constant other factors. DESIGN/METHODOLOGY: The novelty of
      the analysis resides in the dataset and estimation strategy employed. Data is
      derived from a United States population-based chemotherapy order entry system,
      IntrinsiQ Intellidose. Quality/price endogeneity is overcome by employing sample
      selection methods and an estimation strategy that exploits quality variation at
      the molecule-indication level. Pooled diffusion rates across molecule-indication
      pairs are estimated using nonparametric hazard models. FINDINGS: Results suggest
      incremental effectiveness is negatively and nonsignificantly associated with the
      diffusion of new chemotherapies; faster rates of diffusion are positively and
      significantly related to low five-year survival probabilities and measures of
      perceived clinical significance. Results are robust to numerous specification
      checks, including a measure of alternative therapeutic availability. We discuss
      the magnitude and potential direction of bias introduced by several threats to
      internal validity. Evidence of incremental effectiveness does not appear to
      motivate the rate of specialty physician diffusion of new medical treatment; in
      all models high risk of disease mortality and perceptions of therapeutic quality
      are significant drivers of physician use of novel chemotherapies.
      VALUE/ORIGINALITY: Understanding the rate of technological advance across
      different clinical settings, as well as the product-, provider-, and patient
      level determinants of this rate, is an important subject for future research.

PMID- 23156664
TI  - Technology diffusion and substitution of medical innovations.
AB  - PURPOSE: The aim of this paper is to examine the diffusion of a new surgical
      procedure with lower per-case cost and how its diffusion path is affected by the
      simultaneous introduction of a new drug class that may be an effective treatment
      to prevent surgery. In particular, we examine whether a process of technology
      substitution exists that influences the diffusion process of the surgical
      technology. Given their different cost implications, the interaction of these two
      different technologies, surgery and drug intervention, is relevant from the
      perspective of health expenditure. This is of particular interest in health care
      as technology adoption and diffusion has been cited as a major driver of
      expenditure growth. Such expenditure growth has been increasingly targeted
      through the use of market-orientated policy tools aimed at increasing efficiency.
      Our research is thus addressing the question of how economic incentives influence
      the diffusion process and we discuss the impact of a set of incentives on
      hospital behavior. DESIGN/METHODOLOGY: Hospital admission data for the financial
      years 1998/1999 to 2007/2008 in England are used to empirically test the
      contribution of prescription uptake and market-oriented reforms. Dynamic panel
      data models are used to capture any changes in technology preference during the
      period of study. FINDINGS: Our results suggest that the hospital sector exhibits
      a strong new technology preference, tempered by the interaction of competition
      for patients and the ability of the primary care sector to substitute treatments.
      VALUE/ORIGINALITY: Given the current fast technological change, we examine the
      technological race occurring in the health care sector. We account simultaneously
      for the diffusion of different technologies not only within the same typology but
      also with technologies of a different class.

PMID- 23156665
TI  - Health insurance and hospital technology adoption.
AB  - PURPOSE: This chapter discusses the relationship between health insurance and
      hospitals' decisions to adopt medical technologies. I focus on both how the
      extent of insurance coverage can increase incentives to adopt new treatments, and
      how the parameters of the insurance contract can impact the types of treatments
      adopted. METHODOLOGY/APPROACH: I provide a review of the previous theoretical and
      empirical literature and highlight evidence on this relationship from previous
      expansions of Medicaid eligibility to low-income pregnant women. FINDINGS: While
      health insurance has important effects on individual-level choices of health care
      consumption, increases in the fraction of the population covered by insurance has
      also been found to have broader supply side effects as hospitals respond to
      changes in demand by changing the type of care offered. Furthermore, hospitals
      respond to the design of insurance contracts and adopt more or less cost
      effective technologies depending on the incentive system. RESEARCH
      LIMITATIONS/IMPLICATIONS: Understanding how insurance changes supply side
      incentives is important as we consider future changes in the insurance landscape.
      ORIGINALITY/VALUE OF PAPER: With these previous findings in mind, I conclude with
      a discussion of how the Affordable Care Act may alter hospital technology
      adoption incentives by both expanding coverage and changing payment schemes.

PMID- 23156666
TI  - Reframe the health debate.

PMID- 23156667
TI  - What to do when the crisis hits.

PMID- 23156668
TI  - [The chicken beta-globin genes: a model system for studying transcription
      regulation at the level of genomic domains].
AB  - In the last quarter of the XX century, as a result of studies performed on a
      number of model systems, a hypothesis was formulated according to which the
      genome of higher eukaryotes consists of functionally isolated areas named genomic
      domains. Each domain includes one or more genes and a regulatory system that is
      normally active only in respect of this domain and allows it to achieve the
      regulatory autonomy of the neighboring chromosome regions. A genomic domain is
      characterized by the spectra of covalent histone modifications which define the
      boundaries of the domain and the degree of chromatin condensation within it, and
      so, the probability of transcription activation of genes within the domain.
      Development of the domain hypothesis of genome organization became possible to a
      large extent through the study of mechanisms of transcriptional regulation of the
      globin genes in vertebrates. One of the most popular models in this field of
      molecular biology is the chicken beta-globin gene domain. Based on this model
      system, the fundamental principles of complex enhancer action in higher
      eukaryotes have been described, the properties of insulators and functional units
      of enhancers and promoters have been studied, the influence of covalent histone
      modifications on the level of chromatin condensation and their role in the
      regulation of transcription within the domain have been investigated. In this
      review we summarize the data on the study of the chicken beta-globin gene domain,
      as well as consider the domain hypothesis of eukaryotic genome organization.

PMID- 23156669
TI  - [Protein complementation as tool for studying protein-protein interactions in
      living cells].
AB  - Association and degradation of protein complexes play essential role in a
      majority of normal and pathologic processes, which take place in living cell.
      Studying the underlying mechanisms of those interactions would give deeper
      understanding of specific causes of disease progression and would allow
      developing new therapeutic strategies. The majority of technical approaches
      currently used for detecting protein association include in vitro protein
      extraction and purification, whereas more relevant results require methods that
      can be used in vivo. One of a few approaches for in vivo protein association
      detection is based on reporter protein fragment complementation. Reporter systems
      based on protein complementation rely on reconstitution of reporter protein
      fluorescent or enzymatic activity which occurs upon reassociation of protein
      fragments and could be measured by colorimetry, luminometry or fluorimetry.
      Protein complementation is widely used to develop reporter systems for analysis
      of protein interactions, for functional dissection of signal transduction
      pathways and for performing high-throughput screenings to discover new protein
      interaction partners. Currently developed approaches that utilize protein
      fragment complementation have possibilities that extend far beyond simple
      detection of interaction in a pair of proteins.

PMID- 23156670
TI  - [Oncolytic enteroviruses].
AB  - Increasing information concerning molecular biology of viruses and virus-cell
      interactions makes it possible to use viruses as a tool in effort to treat cancer
      diseases. As a rule, tumor cells are highly sensitive to viruses that may be used
      in cancer therapy. Therewith, applications of viral oncolysis in treatment of
      cancer diseases assume maximum possible safety of used viruses for patient and
      environment. Human enteroviruses are one of the most convenient sources to
      generate oncolytic viruses. Many of enteroviruses are non-pathogenic for humans
      or cause mild disease. Progress in genetic engineering permits to develop
      attenuated enterovirus variants with high safety and selectivity. This review
      focuses on the main members of Enterovirus genus, such as Coxsackieviruses, and
      vaccine strains as promising source for development of oncolytic agents,
      applicable for cancer therapy. It reviews data concerning recently developed and
      tested oncolytic variants of enteroviruses and discusses perspectives of their
      application in cancer therapy and problems, concerning their improvement and
      practical use.

PMID- 23156671
TI  - [Recombinational repair in Schizosaccharomyces pombe: the role of mediator
      proteins].
AB  - Repair of double-stranded DNA breaks that occur spontaneously or under the
      influence of external factors, are critical for cell survival. Evolutionarily
      conserved mechanism for error-free recombinational repair plays a major role in
      maintaining genome integrity. Repair pathway is conservative and has a number of
      similarities in lower eukaryotes and vertebrates. This review examines the
      current state of studying the mechanism of recombinational repair double-stranded
      DNA breaks in the fission yeast Schizosaccharomyces pombe, notes the differences
      of this type of repair in Saccharomyces cerevisiae and higher eukaryotes.

PMID- 23156672
TI  - [Detection of nonsense and frame shift mutations in human BRCA1 gene using new
      plasmid vector pPhoA-frame].
AB  - The technique for the detection of frame shift and nonsense mutations in BRCA1
      gene was suggested. The technique presumes the construction of recombinant
      plasmids where the tested DNA fragment placed in-frame with alkaline phosphatase
      gene of Escherichia coli (phoA). A plasmid pPhoA-frame was constructed for such
      analysis, the plasmid contains DNA fragment coding for alkaline phosphatase of E.
      coli. Synthetic DNA fragment with BglII, StuI, ApaI and SacII sites was inserted
      into the DNA fragment coding for alkaline phosphatase of E. coli between Ala218
      and Gly219 codons to facilitate the cloning of BRCA1 gene fragments. Occurrence
      of the frame shift or nonsense mutation in the tested DNA fragment can be
      detected after transformation of E. coli by the recombinant plasmid containing
      the tested fragment. E. coli colonies with the newly constructed recombinant
      plasmids are plated out on the indicator agar. In the case of frame shift or
      nonsense mutation the colonies are not colored, DNA fragments without such
      mutations result in the formation of the blue colonies.

PMID- 23156673
TI  - N-acetylcysteine enhances neuronal differentiation of P19 embryonic stem cells
      via Akt and N-cadherin activation.
AB  - We examined whether N-acetylcysteine (NAC) enhanced embryonic body (EB) formation
      and neuronal differentiation in terms of EB formation, neuronal marker
      (microtubule-associated protein 2; MAP-2) expression, and neuron maturation using
      P19 embryonic stem cells. The size and numbers of EBs were greatly increased,
      together with the up-regulated N-cadherin expression. Also, MAP-2 expression and
      neurite outgrowth were much increased with activation of serine/threonine protein
      kinase (Akt) and blocked by addition of an Akt inhibitor (LY294002). Our results
      suggested that NAC increased EB formation by up-regulating the N-cadherin
      expression. Furthermore, NAC-enhanced neuronal differentiation was mediated by
      activation of Akt.

PMID- 23156674
TI  - [Fragment of mRNA coding part that is complementary to region 1638-1650 of wheat
      18S rRNA functions as a translational enhancer].
AB  - Possible involvement of 18S rRNA fragment 1638-1650 including basements of the
      helices h44 and h28 and nucleotides of the ribosomal decoding site in the cap
      independent translation initiation on plant ribosomes is studied. This rRNA
      fragment is shown to be accessible for complementary interactions within the 40S
      ribosomal subunit. It is found that the sequence complementary to the 18S rRNA
      fragment 1638-1650 is able to enhance efficiency of a reporter mRNA translation
      when placed just after the initiation codon. The results obtained indicate that
      in the course of the cap-independent translation initiation, complementary
      interactions can occur between mRNA coding sequence and 18S rRNA fragment in the
      region of the ribosomal decoding site.

PMID- 23156675
TI  - [Repressional effects of the glutamate antibodies on expression of Dffb gene in
      the brain of rats with experimental Alzheimer's disease].
AB  - The intranasal administration of glutamate antibodies in the dose of 300
      microg/kg one hour after damage on the level of mRNA expression of Dffb gene
      which codes caspase-activated DNase which participates in intranucleosome
      fragmentation of genome DNA in apoptosis was investigated in experimental
      Alzheimer's disease induced by injection of neurotoxic fragment of beta-amyloid
      protein Abeta25-35 in Meynert basal magnocellular nuclei on rats. On the Day 3
      after Abeta25-35 injection is observed significant decrease of the level of mRNA
      expression of Dffb gene in prefrontal cortex in 37%, and in hippocampus in 62% in
      the experiment group versus the control group. These differences were not found
      in the hypothalamus when comparing the experimental and control animals. It was
      suggested that repressive effect of glutamate antibodies on the level of mRNA
      expression of Dffb gene reflects stabilization of processes taking place in brain
      cells in experimental Alzheimer's disease, and in its turn the intensiveness of
      nerve and glial cells apoptotic death is decreased.

PMID- 23156676
TI  - [Early detection of cancer/testis mRNAs in tumor cells circulating in the
      peripheral blood of colorectal cancer patients].
AB  - Recent studies have suggested that mRNAs transcribed from cancer/testis genes
      might be used as biomarkers of cancer cells migrating through the bloodstream.
      Using RT-PCR we evaluated the expression of several cancer/testis mRNAs (MAGEA1
      6, GAGE1-8, NY-ESO-1, SSX1, 2, and 4, XAGE1 and MAGEC1) in primary tumors and
      peripheral blood samples of colorectal cancer patients. The detection rate of at
      least one of the transcripts was 95% (37/39 samples) for primary tumors and 81%
      (52/64 samples) for the peripheral blood. Moreover, selected mRNAs were
      detectable in cellular fraction of the peripheral blood at all stages the disease
      (14 out of 14 cases), whereas in extracellular fraction of plasma were found only
      at stages III and IV. Obtained data open a possibility of early diagnosis of
      colorectal cancer in people at high risk by peripheral blood analysis.

PMID- 23156677
TI  - [Methylation of some miRNA genes is involved in the regulation of their target
      genes RAR-beta2 and NKIRAS1 expression in lung cancer].
AB  - To date, there are more than two thousand human miRNAs, each of them may be
      involved in the regulation of hundreds of protein coding target genes.
      Methylation of CpG-islands, in turn, affects miRNAs gene expression. Our aim was
      to evaluate the role of methylation in the regulation of miRNA gene expression
      and, consequently, in the regulation of expression of target genes in primary
      lung tumors. Using a common collection of non-small cell lung cancer samples we
      performed a comprehensive study, including analysis of the methylation status and
      expression levels of some miRNA genes and their potential target genes on
      chromosome 3: RAR-beta2 and NKIRAS1. Increased frequency of methylation in lung
      tumors compared to histologically normal tissue was revealed for miR-9-1 and miR
      34b/c genes with significant statistics (P < or = 0.05 by Fisher exact test) and
      for miR-9-3 and miR-193a was marginally significant (P < or = 0.1). Significant
      correlation was revealed between alterations of methylation and expression level
      of miR-9-1 gene (P = 5 x 10(-12) by Spearman) in the lung tumors, this suggests
      the role of methylation in the regulation of expression of this miRNA genes.
      Besides, a statistically significant negative correlation (P = 3 x 10(-12)-5 x
      10(-13) by Spearman) was found between alterations of expression levels of miR-9
      1 and miR-17and RAR-beta2 target gene and also between expression level
      alterations of miR-17 and NKIRAS1 that was not previously analyzed. The inverse
      relationship between expression levels of miRNA genes and their target genes is
      consistent with the known mechanism of suppression of protein coding genes
      expression under the action of miRNAs. For the first time significant
      correlations (P = 3 x 10(-10)-4 x 10(-13) by Spearman) were shown between
      alterations of methylation status of miRNA genes (miR-9-1, miR-9-3, miR-34b/c,
      miR-193a) and the expression level of RAR-beta2 target gene and between
      alterations of methylation status of miR-34b/c, and miR-193a and the expression
      level of NKIRAS1 target gene in the primary lung tumors, which suggests the
      possibility of indirect effects of methylation of miRNA genes on expression level
      of target genes.

PMID- 23156678
TI  - [Heterogeneous expression of CD38 gene in tumor tissue in patients with
      colorectal cancer].
AB  - The CD38 gene codes a membrane protein which takes part in cell adhesion and
      catalyzes the formation of cyclic ADP-ribose. Using RT-PCR method we tested the
      presence of full-size and alternative forms of mRNA CD38 in samples of tumor
      tissue of patients with colorectal cancer and in tumor cell lines. It was shown
      that there are the cells in the tumor tissue which expressed CD38 gene. In tumor
      tissue of patients the alternative form of mRNA CD38 was detected less frequently
      than full-size form. Cells of lines Colo-205, T-84, HCT15 and HCT116 contained
      mRNA CD38, in cells of lines Caco-2 and SW-620 mRNA CD38 was absent. In cells of
      tumor tissue on the first stage of colorectal cancer CD38 gene was expressed in
      100% of cases. On the second, third and fourth stages of the disease gene
      expression was observed less often. The frequency of mRNA CD38 detection not
      depend on tumor localization, tumor grade and presence of metastases. Using
      method of restriction analysis CpG methylation was detected in binding sites of
      transcription factor Sp1 and receptor of retinoic acid (RARE) in all tested
      samples of tumor tissue independently of the presence or absence of mRNA CD38.
      The obtained data suggest that in the tumor cells of patients with colorectal
      cancer the expression of the CD38 gene is heterogeneous.

PMID- 23156679
TI  - [Irregular activity oscillations of rotary molecular motor. A simple kinetic
      model of F1-ATPase].
AB  - F1-ATPase is a catalytic portion of the rotary molecular motor, F1Fo-ATP
      synthase. Cooperative ATP hydrolysis at the three catalytic sites of the F1
      ATPase is connected with rotation of the central gamma-subunit inside a cylinder
      made of three a subunits and three beta subunits. Various experimental works have
      shown that the gamma-subunit rotates with irregular dwells. A simple kinetic
      model of this paper explains dwells during rotation as a result of the
      deterministic chaos. It is shown that the deterministic chaos occurs under the
      rate constants close to the known experimental estimations. Time duration of
      dwells in the model are close to those observed experimentally. Our model
      explains the known irregular occupancy of catalytic sites of F1-ATPase by
      nucleotides.

PMID- 23156680
TI  - [Protein families specific for plastoms in small taxonomy groups of algae and
      protozoa].
AB  - Protein clustering is useful for refinement of protein annotation as well as
      cluster finding by its phylogenetic profile. We performed clustering of plastid
      encoded proteins from Rhodophyta as well as other plastid containing species
      related to Rhodophyta branch on species tree. Data base for cluster finding by
      its phylogenetic profile is available on http://lab6.iitp.ru/ppc/redline. By
      means of the database distinctive proteins for plastoms from small taxonomy
      groups of algae and protozoa were found. We performed finding and analysis of RNA
      polymerases encoded in Apicomplexa nuclei.

PMID- 23156681
TI  - Universal primers for amplification of the complete mitochondrial control region
      in marine fish species.
AB  - Through multiple alignment analysis of mitochondrial tRNA-Thr and tRNA-Phe
      sequences from 161 fishes, new universal primers specially targeting the entire
      mitochondrial control region were designed. This new primer set successfully
      amplified the expected PCR products from various kinds of marine fish species,
      belonging to various families, and the amplified segments were confirmed to be
      the control region by sequencing. These primers provide a useful tool to study
      the control region diversity in economically important fish species, the possible
      mechanism of control region evolution, and the functions of the conserved motifs
      in the control region.

PMID- 23156682
TI  - [Development of biochip for determination of Y-haplogroups occuring in Russian
      populations].
AB  - Biochip has been developed which allowed to determine the following Y-chromosome
      haplogroups: C, DE, G, H, I, J, L, N, O, R in a DNA sample. The following SNPs
      were choosen as haplogroup markers: M130, M145, P257, M69, U179, M304, M185,
      M231, M175, P224, correspondingly. The genotyping included two-round PCR with
      fluorescent label incorporation into PCR product followed by hybridization with
      immobilized probes on biochip. The analysis of fluorescent signal ratios in pairs
      of immobilized probes "wild-type probe"--"group specific probe" for each of
      choosen polymorphic markers showed high accuracy of Y-haplogroup genotyping using
      biochip. The reliability of genotyping was confirmed by direct sequencing.

PMID- 23156683
TI  - [Co-localization of selenium-containing protein V (seIV) and its partners in
      mammalian cells].

PMID- 23156684
TI  - [Ultramicrobacteria: Formation of the concept and contribution of
      ultramicrobacteria to biology].

PMID- 23156685
TI  - [Changes in the species composition of a thermotolerant community of acidophilic
      chemolithotrophic microorganisms upon switching to the oxidation of a new energy
      substrate].

PMID- 23156686
TI  - [Rates of sulfide mineral oxidation by acidophilic chemolithotrophic microbial
      communities from various sources].

PMID- 23156687
TI  - [Differences in the carbohydrate composition between the yeastlike and mycelial
      cells of Mucor hiemalis].

PMID- 23156688
TI  - [Characterization of the Pragia fontium Lipopolysaccharides].

PMID- 23156689
TI  - Characterization of the novel xylanase from the thermophilic Geobacillus
      thermodenitrificans JK1.
AB  - Thermophilic strain JK1 was isolated from compost using xylan as a single carbon
      source. On the basis of 16S rRNA gene phylogenetic analysis and spo0A gene
      sequence similarity analysis, strain JK1 was identified as Geobacillus
      thermodenitrificans strain. During the exponential culture growth, the strain JK1
      was found to produce the single xylan degrading enzyme -45 kDa in size. Xylose
      was not an inducer of this xylanase. Cloning, expression and characterization of
      the recombinant xylanase were performed. Xylanase of G. thermodenitrificans JK1
      was cellulase-free; pH and temperature optimums were found to be 6.0 and 70
      degrees C, respectively. The metal ions Na+, K+, Ca2+, and Co2+ showed partial
      inhibition of the activity, while Mn2+ had slight stimulating effect on the
      enzymatic activity. Recombinant xylanase was thermostable over the temperature
      range of 55-70 degrees C. It presented the highest stability after incubation at
      55 degrees C for 60 min showing 84% residual activity. 50% residual activity was
      revealed after incubation at 60 degrees C for 60 min as well as at 65 and 70
      degrees C for 30 min. Results of the thermostability experiments showed xylanase
      of JK1 having quite low thermostability when compared with the respective enzymes
      of the other geobacilli.

PMID- 23156690
TI  - [Cell wall teichoic acids of Bacillus licheniformis VKM B-511T, Bacillus pumilus
      VKM B-508T, and other strains previously assigned to Bacillus pumilus].

PMID- 23156691
TI  - [Reactivation of dormant and nonculturable bacterial forms from paleosoils and
      subsoil permafrost].

PMID- 23156692
TI  - [A novel filamentous planctomycete of the Isosphaera-Singulisphaera group
      isolated from a Sphagnum peat bog].

PMID- 23156693
TI  - [ Change in the temperature preferences of Beauveria bassiana sensu lato isolates
      in the latitude gradient of Siberia and Kazakhstan].

PMID- 23156694
TI  - [First report on bacteria of the family Spirochaetaceae from digestive tract of
      endemic gastropods from Lake Baikal].

PMID- 23156695
TI  - [Factors controlling the activity of the microbial community of the alkaline Lake
      Beloe (Transbaikal Region)].

PMID- 23156696
TI  - [Microbial decomposition of organic matter in the bottom sediments of small lakes
      of the urban landscape (Lithuania)].

PMID- 23156697
TI  - [Diversity of cultivable bacteria isolated from the water column and bottom
      sediments of the Kara Sea shelf].

PMID- 23156698
TI  - [Application of the inhibition of bacterial bioluminescence test for assessment
      of toxicity of carbon-based nanomaterials].

PMID- 23156699
TI  - A simple purification procedure of D-amino-acid oxidase from Candida
      guilliermondii H(see symbol)-4.
AB  - D-amino-acid oxidase (EC 1.4.3.3) was purified about 1480-fold from the yeast
      Candida guilliermondii H(see symbol)-4 using chromatofocusing method. The
      purification procedure gave an enzyme preparation which is greater than 90%
      homogenous on SDS-polyacrylamide gels with a specific activity of 11.54 U/mg at
      30 degrees C with D-proline as substrate with the yield of total activity 9.3%.
      The molecular weights of subunit and native enzyme were determined to be 38.4 and
      78.6 kDa by SDS-polyacrylamide gel electrophoresis and gel-filtration,
      respectively, suggesting that the native enzyme exists as a homodimer. A single
      molecular form with an isoelectric point of 6.85 was detected in analytical
      isoelectrofocusing. The optimum pH and temperature were 8.0 and 33 degrees C. An
      enzyme shows stability in the pH range from 7.4 to 9.0 and at the temperature no
      higher than 38 degrees C. Activation energy for D-amino-acid oxidase reaction was
      calculated to be 60 kJ/mol at 30 degrees C. The strict D-isomer specificity of
      the enzyme is confirmed, since no reaction could be detected with L-amino acids,
      and a large number of D-amino acids could be substrates for this enzyme. K(m) and
      V(max) values were determined for D-proline and D-alanine, which, among 22
      tested, were the best substrates of the enzyme. D-amino-acid oxidase from the
      yeast C. guilliermondii is a flavoprotein oxidase in which the prosthetic group
      is tightly, but not covalently, bound FAD. The enzyme is completely inhibited by
      sodium benzoate, SH-oxidizing agents, but not by sodium azide, toluene or
      chloroform.

PMID- 23156700
TI  - [Green microalgae isolated from associations with white sea invertebrates].

PMID- 23156701
TI  - Iron storage disorders in captive wild mammals: the comparative evidence.
AB  - Excessive burden of iron, or iron storage disease (ISD), has been reported in a
      large variety of captive mammal species, including browsing rhinoceroses; tapirs;
      fruit bats; lemurs; marmosets and some other primates; sugar gliders; hyraxes;
      some rodents and lagomorphs; dolphins; and some carnivores; including procyonids
      and pinnipeds. This report collates the comparative evidence for species'
      susceptibility, recognizing that the data for mammal species are limited.
      Differences reported in the occurrence of ISD between facilities, or within
      facilities over periods that span management changes, have been reported in
      individual cases but are underused in ISD research. Given the species
      composition, the hypothesis that evolutionary adaptations to the iron content and
      availability in the natural diet determine a species' susceptibility to ISD (in
      the face of deviating iron content and availability in diets offered in
      captivity) seems plausible in many cases. But exceptions, and additional species
      putatively susceptible based on this rationale, should be investigated. Whereas
      screening for ISD should be routine in zoo animal necropsy, screening of live
      individuals may be implemented for valuable species, to decide on therapeutic
      measures such as chelator application or phlebotomy. Whatever the reasons for ISD
      susceptibility, reducing dietary iron levels to maintenance requirements of the
      species in question seems to be a logical, preventive measure.

PMID- 23156702
TI  - Iron homeostasis and its disorders in mice and men: potential lessons for rhinos.
AB  - During the last decade, there have been remarkable advances in the understanding
      of iron homeostasis and its disorders. This review summarizes our presentation at
      the International Workshop on Iron Storage Disease in Black Rhinos that was held
      in Orlando, Florida, USA, from 23 to 26 February 2011, and it is directed to
      veterinarians and nutritional experts who treat rhinoceroses. This review
      summarizes the current knowledge in humans and mice regarding the physiology and
      molecular basis of iron overload, and it explores how it can be applied to the
      problem of iron overload in captive rhino populations.

PMID- 23156703
TI  - Avian iron storage disease: variations on a common theme?
AB  - Many frugivorous avian species kept in captivity develop iron storage disease
      (ISD) as indicated by high concentrations of hepatic iron and hemosiderin
      deposits in hepatocytes or phagocytes. In several susceptible species fed diets
      containing moderate levels of iron, ISD develops because of an inability to match
      rates of iron absorption to tissue needs. Evidence suggests that the
      pathophysiologic basis of excess iron absorption is due to high levels of
      expression of divalent metal transporter-1 that transports iron into enterocytes
      in the proximal intestine, and ferroportin that exports iron to the circulation.
      The regulatory basis for this inability to sufficiently down-regulate iron
      absorption is unknown, but disruptions in the hepcidin-ferroportin axis are
      likely candidates based on recent research in humans and laboratory rodents. It
      is likely that ISD-susceptible avian species evolved on foods that were very low
      in bioavailable iron, so there was strong selection pressure for the efficient
      capture of the small amount of dietary iron but low selection pressure for
      preventing iron toxicities. Thus, the transporters and regulatory networks for
      iron absorption seem to be heavily skewed toward iron storage even when food
      items that are high in iron are consumed. Infections, trauma and neoplasias that
      trigger an acute phase response may exacerbate ISD in susceptible species and may
      be the primary cause in species that are normally resistant to ISD (i.e., those
      that are normally able to shut down intestinal iron absorption when iron stores
      are replete). The evolutionary basis that resulted in some avian species to be
      susceptible to ISD (e.g., dietary cause) seems to differ from many inherited ISD
      disorders in humans that are thought to have evolved to bolster protection
      against infectious diseases. However the evolutionary basis of ISD in other
      mammalian species might be more similar to that in ISD-susceptible avian species.

PMID- 23156704
TI  - Hemochromatosis and fatty liver disease: building evidence for insulin resistance
      in bottlenose dolphins (Tursiops truncatus).
AB  - Hemochromatosis in bottlenose dolphins (Tursiops truncatus) is associated with
      high postprandial plasma insulin levels, suggestive of insulin resistance. In
      humans, insulin resistance is associated with liver pathologies, including
      excessive iron deposition and nonalcoholic fatty liver disease. Dolphin liver
      tissues, in addition to excessive iron storage, were evaluated for other
      pathologies supportive of underlying insulin resistance. Archived liver tissues
      collected postmortem during 1985-2010 from 18 dolphins (median age 27.9 yr, range
      0.7-51.4) that were part of the Navy Marine Mammal Program's managed collection
      were assessed for the presence and severity of hemosiderin deposition, fatty
      liver disease, and hepatitis. Demographics, clinical pathology values, and
      percentage weight loss were compared among dolphins with and without these
      changes. Twelve (66.7%) dolphins had mild to moderate hemosiderin deposition, 7
      (38.9%) had mild to severe fatty liver disease, and 11 (61.1%) had mild to
      moderate hepatitis. Of the 12 dolphins with hemosiderosis, deposition occurred in
      the Kupffer cells among 11 (91.7%). Dolphins with fatty liver disease were more
      likely to have higher postprandial serum hyperglycemia (>140 mg/dl), leukocytosis
      (>11,000 cells/microl), and hyperglobulinemia (>3.5 g/dl). Unlike in many
      nonhuman terrestrial animals, fatty liver disease was not associated with rapid
      weight loss or hypoglycemia. Interestingly, there were no significant
      associations among dolphins with hemosiderosis, fatty liver disease, and
      hepatitis. This study supports that both hemochromatosis and fatty liver disease
      were present in the dolphin study population, and histopathology and clinical
      pathology among these animals suggest a nonhereditary, metabolic etiology.
      KEYWORDS: Bottlenose dolphin, fatty liver disease, hemochromatosis,
      hemosiderosis, hepatic lipidosis, hepatitis, Tursiops truncatus.

PMID- 23156705
TI  - Black rhinoceros (Diceros bicornis) natural diets: comparing iron levels across
      seasons and geographical locations.
AB  - Although excessive iron storage in black rhinoceros (Diceros bicornis) has been a
      cause for continuous concern over the last four decades and differences in the
      iron content of diet items fed in captivity and in the wild have been documented,
      no reports exist on the iron content of the total diet ingested by free-ranging
      animals. Here, the results of field studies using backtracking to record the
      ingested diets of black rhinoceros from three habitats across three seasons are
      reported. Levels of iron and of condensed tannins, which might reduce iron
      availability, averaged at 91 +/- 41 ppm dry matter and 3.0 +/- 1.0% dry matter,
      respectively, across all habitats and seasons. Although geographic and seasonal
      variation was significant, these differences are of a much lower magnitude than
      differences between the averages of these diets and those fed to black rhinoceros
      in captivity. The results can provide guidelines for the iron content of diets
      designed for black rhinoceros and suggest that the effect of tannins in these
      species should be further investigated.

PMID- 23156706
TI  - Serum iron and selected biochemical values in free-ranging black rhinoceros
      (Diceros bicornis) from South Africa.
AB  - Serum samples collected from 20 black rhinoceros (Diceros bicornis) were analyzed
      for iron values from six different areas in South Africa. In addition,
      biochemical profiles were performed on individual samples. Comparisons of iron
      values from free-ranging black rhinoceros and from 28 free-ranging white
      rhinoceros (Ceratotherium simum) were conducted by location and age. Among the
      free-ranging black rhinoceros, samples were compared from different regions to a
      set of samples from black rhinoceros that had been captured and held in bomas.
      Serum iron levels were not significantly different (P = 0.55) among the three
      locations with more than one animal (medians 5.57, 5.70, 6.47 ppm), but the
      median value from the boma group was significantly lower (2.91 ppm; P = 0.042),
      contrary to previous studies. Similar to reports in captive black rhinos, serum
      iron levels appeared to show a trend toward increasing values between subadult
      and adult animals, although differences were not statistically significant among
      black rhinoceros. Comparison of serum iron levels between free-ranging black and
      white rhinoceros showed significantly higher median value in black rhinoceros
      (5.73 ppm) versus white rhinoceros (3.38 ppm, P= 0.001). Other significant
      differences (P < 0.05) in biochemical values between species included lower
      median aspartate aminotransferase (37 versus 76.5 U/L), higher copper (1.50
      versus 1.34 ppm), higher zinc (1.36 versus 0.37 ppm), lower total protein (8.0
      versus 10.35 g/dL), higher gamma glutamyltransferase (13.0 versus 12.5 U/L), and
      lower globulin (6.6 versus 7.6 g/dL) in black rhinoceros. Further investigations
      should be conducted to examine the role of age, location, and time in boma
      confinement on iron values in South African rhinoceros to understand iron
      metabolism in these species.

PMID- 23156707
TI  - A potential link between insulin resistance and iron overload disorder in
      browsing rhinoceroses investigated through the use of an equine model.
AB  - Iron overload disorder afflicts captive rhinoceros but has not been documented in
      the wild. The specific cause for the disorder has not been identified but is
      likely associated with diet and management. Compared with wild counterparts,
      captive rhinoceros eat diets containing more iron, have greater fat stores, and
      exercise less. It has been suggested that the problem may be linked to
      development of insulin resistance in the captive population. Given that
      controlled experiments with sufficient numbers of rhinoceros are logistically not
      possible, an equine model was used to look for a relationship between iron status
      and insulin resistance; the nutritional requirements of horses are used as a
      guide for rhinoceros, because they have similar gastrointestinal tracts. Sixteen
      horses were tested to determine blood insulin responses to an oral drench of
      dextrose (0.25 g/kg bodyweight) and a meal of pelleted corn (1.5 g/kg
      bodyweight). Fasting blood samples were taken 30 and 0 min before administration.
      Further blood samples were taken every 30 min for 4 hr after administration to
      determine peak insulin and total area under the insulin curve (AUC). Fasting
      samples were tested for serum ferritin concentrations. Correlations were
      determined between ferritin and peak insulin concentrations and insulin AUC after
      administration of oral dextrose and pelleted corn. The strongest correlation was
      between ferritin and insulin AUC after dextrose administration (r = 0.61; P =
      0.01) followed by AUC after feeding a meal of pelleted corn (r = 0.60; P = 0.01),
      with the correlation for peak insulin being 0.53 (P = 0.03) after dextrose
      administration and 0.56 (P = 0.02) after pelleted corn. When evaluating responses
      by gender, a significant correlation existed only for females, influenced by one
      insulin resistant individual. These data suggest a potential link between insulin
      resistance and body stores of iron and also suggest that approaches to reduce the
      susceptibility to insulin resistance should be incorporated into management of
      captive browsing rhinoceros.

PMID- 23156708
TI  - Browse diversity and iron loading in captive sumatran rhinoceroses (Dicerorhinus
      sumatrensis): a comparison of sanctuary and zoological populations.
AB  - Iron storage disease (ISD) is now recognized as a serious clinical disorder
      acquired by two species of browsing rhinoceroses, the African black (Diceros
      bicornis) and the Asian Sumatran (Dicerorhinus sumatrensis) rhinoceroses, when
      displaced from their natural habitats. The most complete knowledge of ISD comes
      from studies of the black rhinoceros, but the Asian species is also at risk.
      Sumatran rhinoceroses housed in traditional zoological settings outside of range
      countries have suffered significant morbidity and mortality potentially related
      to ISD induced by diet and/or other confinement conditions. With so few animals
      in captivity, very little information exists on iron loading in the Sumatran
      rhinoceros. To better characterize the problem, we retrospectively compared
      captive management conditions of Sumatran rhinoceroses housed under traditional
      zoological care with those in two native sanctuary environments. In general, zoo
      rhinoceroses are offered a paucity of plants and browse species compared with
      their sanctuary and wild counterparts managed in native rainforest habitats. Iron
      analyte levels and limited histopathologic observations in these populations
      suggest variable tendencies to overload iron, dependent upon differences in
      managed diet and individual food preferences. More detailed investigation of
      these markedly dissimilar ex situ populations is warranted to better understand
      the role of nutrition and other conditions affecting iron loading in browser
      rhinoceroses.

PMID- 23156709
TI  - Plant phenolics and their potential role in mitigating iron overload disorder in
      wild animals.
AB  - Phenolic compounds are bioactive chemicals found in all vascular plants but are
      difficult to characterize and quantify, and comparative analyses on these
      compounds are challenging due to chemical structure complexity and inconsistent
      laboratory methodologies employed historically. These chemicals can elicit
      beneficial or toxic effects in consumers, depending on the compound, dose and the
      species of the consumer. In particular, plant phenolic compounds such as tannins
      can reduce the utilization of iron in mammalian and avian consumers. Multiple zoo
      managed wild animal species are sensitive to iron overload, and these species
      tend to be offered diets higher in iron than most of the plant browse consumed by
      these animals in the wild and in captivity. Furthermore, these animals likely
      consume diets higher in polyphenols in the wild as compared with in managed
      settings. Thus, in addition to reducing dietary iron concentrations in captivity,
      supplementing diets with phenolic compounds capable of safely chelating iron in
      the intestinal lumen may reduce the incidence of iron overload in these animal
      species. It is recommended to investigate various sources and types of phenolic
      compounds for use in diets intended for iron-sensitive species. Candidate
      compounds should be screened both in vitro and in vivo using model species to
      reduce the risk of toxicity in target species. In particular, it would be
      important to assess potential compounds in terms of 1) biological activity
      including iron-binding capacity, 2) accessibility, 3) palatability, and 4)
      physiological effects on the consumer, including changes in nutritional and
      antioxidant statuses.

PMID- 23156710
TI  - Management strategies of iron accumulation in a captive population of black
      rhinoceroses (Diceros bicornis minor).
AB  - During routine health screens for black rhinoceroses (Diceros bicornis minor) in
      a captive setting, serum iron and ferritin were analyzed as well as total iron
      binding capacity and total iron saturation. Trends for ferritin and percent iron
      saturation showed steady increases since 2003 in four of four animals (three
      males; one female) with two animals (one male; one female) consistently showing
      higher elevations over conspecifics. The historical diet had been comprised of a
      commercial or in-house complete pelleted feed; several species of fresh browse,
      Bermuda grass, alfalfa and timothy hays, as well as enrichment and training items
      (apples, carrots, sweet potatoes, and a small amount of leafy greens and
      vegetables). In 2009, one of the three male rhinoceroses showed a threefold
      increase in ferritin and concurrently exhibited clinical signs of lethargy,
      decreased appetite, and disinterest in training. The lone female showed a twofold
      increase; she also became reproductively acyclic in the prior year. The male was
      immobilized for examination and phlebotomy. During the same time period, a new
      version of the complete pelleted feed, with a reduced amount of iron, was
      introduced. Subsequent to the diet change, the male's ferritin levels have
      consistently declined, and the female started cycling again. Even with these
      corrective steps to reduce iron levels, levels of iron saturation remained high,
      and ferritin levels were still above 1,500 ng/ml. Therapeutic phlebotomy was
      instituted via a rigorous training program that allowed phlebotomies over a 30
      min time frame. This was possible because of a long-term training program for the
      animals, consistent training personnel, routine collection of samples on a
      monthly basis, and general comfort level of the animals in the restraint chute.
      The results of this integrated approach showed some significant improvements and
      an overall positive impact on the animals.

PMID- 23156711
TI  - Review of laboratory and necropsy evidence for iron storage disease acquired by
      browser rhinoceroses.
AB  - Necropsies of two browser rhinoceroses, African black (Diceros bicornis) and
      Sumatran (Dicerorhinus sumatrensis), often reveal extensive iron-pigment
      deposition in various tissues. This condition (hemosiderosis) has not been
      observed in species that are natural grazers, African white (Ceratotherium simum)
      and Asian greater one-horned (Indian; Rhinoceros unicornis), nor in any species
      free ranging in the wild. The causes, clinical significance, and consequences of
      captivity-acquired hemosiderosis have remained controversial despite two decades
      of compelling evidence that iron tends to accumulate logarithmically in all
      members of affected species in proportion to periods of expatriation; total-body
      iron loads can reach 10-fold in less than 3 yr and eventually exceed reference
      ranges by two to three orders of magnitude; iron overburdens are accompanied by
      laboratory and histopathologic evidence of cellular injury, necrosis and other
      clinical consequences characteristic of chronic pathologic iron storage
      [corrected] disorders (ISD) in humans and other species (hemochromatosis); and
      that ISD develops in many other exotic wildlife species displaced from their
      natural habitats. The historical evolution of evidence establishing the
      development of pathologic ISD in browser (but not in grazer) rhinoceroses and the
      possible relevance of ISD to other conditions affecting these two species will be
      reviewed. Evidence reviewed includes new as well as published data derived from
      quantitative measurements of iron analytes in sera and necropsy tissues and
      histopathologic evaluations of current and past necropsies of captive and free
      ranging rhinoceroses of all four available species. The evolutionary, husbandry,
      and conservation implications of ISD in rhinoceroses are relevant to
      understanding ISD acquired by many other species of exotic wildlife when
      displaced from their natural environments.

PMID- 23156712
TI  - IOD in rhinos--veterinary group report: report from the Clinical Medicine and
      Pathology Working Group of the International Workshop on Iron Overload Disorder
      in Browsing Rhinoceros (February 2011).

PMID- 23156713
TI  - IOD in rhinos--nutrition group report: Report from the Nutrition Working Group of
      the International Workshop on Iron Overload Disorder in Browsing Rhinoceros
      (February 2011).

PMID- 23156714
TI  - IOD in rhinos--epidemiology group report: report from the Epidemiology Working
      Group of the International Workshop on Iron Overload Disorder in Browsing
      Rhinoceros (February 2011).

PMID- 23156715
TI  - IOD in rhinos--immunity group report: report from the Immunity, Genetics and
      Toxicology Working Group of the International Workshop on Iron Overload Disorder
      in Browsing Rhinoceros (February 2011).

PMID- 23156716
TI  - [Roles of gap junctions in proliferation mediated by Hcy in the spontaneous
      hypertensive rat vascular smooth muscle cells].
AB  - OBJECTIVE: To investigate whether homocysteine (Hcy) participates the
      proliferation of the spontaneously hypertensive rat(SHR) vascular smooth muscle
      cell (VSMCs) and the molecular mechanism. METHODS: The rat's arota were removed.
      The primary SHR VSMCs were isolated and cultured in vitro, then the SHR VSMCs
      were divided into four groups: (1) control group, (2) Hcy group, (3) 18alpha
      glycyrrhetinic acid (GA) group, (4) Hcy + 18alpha-GA group. We detected
      proliferation of the SHR VSMCs by MTT and flow cytometry. The expression and co
      localization of the connexin (Cx) 43 and Cx40 proteins in the SHR VSMCs were
      deteced by immunofluorescence. The expression of the Cx43 and Cx40 proteins in
      SHR VSMCs were detected by Western blot. The molecular dye transfer method
      (scrape dye transfer method) was applied to detect the gap junction function in
      the SHR VSMCs. RESULTS: (1) The Cx43 and Cx40 proteins expression in the SHR
      VSMCs were positive, confocal microscopy supported the co-localization of Cx43
      and Cx40 in the cytoplasm. (2) The S value deteced by cell cycle and A value
      detected by MTT in the Hcy group were increased obviously compared with those in
      the control group (P < 0.05), decreased in 18alpha-GA group (P < 0.05). Compared
      with the Hcy group, the S and A value in the Hcy + 18alpha-GA group were
      significantly decreased, respectively (P < 0.05). (3) The expression of Cx43 and
      Cx40 proteins in Hcy group were increased compared with the control group (P <
      0.05), decreased in 18alpha-GA group (P < 0.05). Compared with the Hcy group, the
      expression of Cx43 and Cx40 proteins in the Hcy + 18alpha-GA group were
      significantly decreased, respectively (P < 0.05). (4) The function of gap
      junction detected by scrape dye transfer method in the Hcy group were enhanced
      compared with the control group (P < 0.05), weakened in the 18alpha-GA group (P <
      0.05). Compared with the Hcy group,the function of gap junction in the Hcy +
      18alpha-GA group was significantly weakened (P < 0.05). CONCLUSION: Hcy can
      enhance the function of gap junctional to stimulate the proliferation of SHR
      VSMCs through the expression of Cx43 and Cx40 proteins promoted.

PMID- 23156717
TI  - [Generation of Tau/App/PS1 triple-transgenic mouse model and the study of its
      biological characteristics].
AB  - OBJECTIVE: To establish the triple-transgenic mouse model and study their
      biological characteristics by molecular biology, behavior and pathology. METHODS:
      Hybrid the Tau and amyloid precursor protein (APP)/presenilins (PS1) transgenic
      mouse, the genotype of offspring mice were identified by PCR. Transcribed target
      genes were detected by RT-PCR. The protein expression of exogenous genes was
      detected by Western-blot. The pathological change of neurofibrillary tangles and
      senile plaque were observed by Bielschowsky silver staining and ABC
      immunohistochemical method. The changes time of learning and memory were observed
      by Morris water maze. RESULTS: APP, PS1 and Tau genes were transcript in
      Tau/APP/PS1 mice. In 6 to 8 months old Tau/APP/PS1 mice, the neurofibrillary
      tangles and senile plaque could be found in cortex and hippocampus. In 6 months
      old Tau/APP/PS1 mice, the learning and memory abilities were worse. CONCLUSION:
      With the behavior change and pathological changes in Tau and beta-amyloid protein
      (AP), the Tau/APP/PS1 triple-transgenic mice can be used as a further study
      animal model of AD's pathogenesis and the target of drug treatment.

PMID- 23156718
TI  - [The variation of PPAR pathway molecules in the lung tissue of rats under
      hyperbaric oxygen exposure].
AB  - OBJECTIVE: To study the expression pattern of peroxisome proliferator-activated
      receptor (PPAR) pathway molecules in rat lung tissue under hyperbaric oxygen
      exposure. METHODS: Twenty seven male SD rats were randomly divided into
      hyperbaric normoxia group (0.23 MPa air), hyperbaric oxygen treatment time series
      group (0.23 MPa oxygen, were exposed for 2 h, 4 h, 6 h or 8 h), continuous small
      flow of ventilation to maintain cabin O2 concentration > 99%. HE staining of lung
      tissue morphological changes and application oligo microarray to each time point
      lung were observed. Part of the PPAR pathway genes were validated by RT-PCR.
      RESULTS: Compared with hyperbaric normoxia group, the lung injury caused by
      hyperbaric oxygen treatment gradually deteriorated during the time series.
      Expression microarray analysis of gene ontology (Go) enrichment analysis results
      in a class of PPAR pathway class included multiple PPAR pathway molecule. RT-PCR
      results suggested that PPAR-8 and PPAR-Y were up-regulated in the lung tissue
      after a long time exposure to hyperbaric oxygen. CONCLUSION: Pro-longed
      hyperbaric oxygen exposure causing pulmonary oxygen toxicity can induce the
      activation of the PPAR pathway.

PMID- 23156719
TI  - [Effects of taurine on the ultrastructure and P2X7 receptor expression in brain
      following traumatic brain injury in rats].
AB  - OBJECTIVE: To explore the effects of taurine on the ultrastructure and P2X7
      receptor protein expression in brain following traumatic brain injury (TBI) in
      rats. METHODS: Forty male SD rats, were divided randomly into four groups that
      were sham-operated group, TBI group, TBI plus low-dose taurine group and TBI plus
      high-dose taurine group. The TBI model was established by Marmarou's method, the
      expression of P2X7 receptor protein in parietal cortex and hippocampus was
      detected by the immunohistochemical method, the ultrastructure of parietal cortex
      were observed by transmission electron microscope. RESULTS: Compared with sham
      operated group, the positive expression cells of P2X7 receptor protein in
      parietal cortex and hippocampus of TBI group were significantly increased (P <
      0.01). Compared with TBI group, the positive expression cells of P2X7 receptor
      protein in parietal cortex and hippocampus of TBI plus low-dose taurine group and
      TBI plus high-dose taurine group were significantly decreased (P <0.01 or P
      <0.05). Compared with TBI plus low-dose taurine group, the positive expression
      cells of P2X7 receptor protein in parietal cortex and hippocampus of TBI plus
      high-dose taurine group were significantly decreased (P < 0.05 or P < 0.01). The
      pathological damage of parietal cortex in the TBI plus high-dose taurine group
      was obviously lightened. CONCLUSION: Taurine exerts the neuroprotective effect on
      TBI in rats, the protective mechanism might be associated with down-regulating
      the expression of P2X7 receptor protein in parietal cortex and hippocampus.

PMID- 23156720
TI  - [Effects of microRNA-1 on negatively regulating L-type calcium channel beta2
      subunit gene expression during cardiac hypertrophy].
AB  - OBJECTIVE: To investigate the negative regulation of microRNA-1 (miR-1) on L-type
      calcium channel beta2 subunit (Cavbeta 2) during cardiomyocyte hypertrophy and
      its mechanism. METHODS: Cardiomyocyte hypertrophy was induced by isoproterenol
      (ISO). The cell surface area was measured by image analysis system (HJ2000). The
      targets of miR-1 were predicted by online database microCosm. The 3' untranslated
      region sequence of Cavbeta 2 was cloned into luciferase reporter vector and then
      transiently transfected into HEK293 cells. The luciferase activities of samples
      were measured to verify the expression of luciferase reporter vector. The
      expression of atrial natriuretic peptide (ANP), beta-myosin heavy chain (beta
      MHC), miR-1 and the Cavbeta 2 mRNA were detected by qRT-PCR. The protein
      expression of Cavbeta 2 was detected by Western blot. The level of miR-1 was up
      regulated by miR-1 mimic transfection and the expression level of Cavbeta 2 was
      down-regulated by RNAi, then effects of which on cardiomyocyte hypertrophy were
      investigated. RESULTS: (1) The expression of miR-1 was significantly reduced in
      cardiomyocyte hypertrophy. Upregulating the miR-1 level could suppress the
      increase of cell surface area, the expression of ANP and beta-MHC mRNA (P <
      0.05). (2) Cavbeta 2 was the one of potential targets of miR-1 by prediction
      using online database microCosm. The luciferase activities of HEK293 cells with
      the plasmid containing miR-1 and wide type Cavbeta 3' UTR sequence was
      significantly decreased when compared with that of control group (P < 0.01). Up
      regulation of the miR-1 level could suppress the protein expression of Cavbeta 2.
      (3) The expression of Cavbeta 2 was significantly increased in cardiomyocyte
      hypertrophy induced by ISO. Downregulation of Cavbeta by RNAi could markedly
      inhibit the increase of cell surface area, the expression of ANP and beta-MHC
      mRNA. CONCLUSION: Cavbeta2 is one of potential targets of miR-1 by bioinformatics
      prediction. The experiment data confirms that Cavbeta2 is truly the target of miR
      1. MiR-1 can negatively regulate the expression of Cavbeta 2, resulting in the
      decrease of intracellular Ca2+ content and the attenuation of cardiomyocyte
      hypertrophy.

PMID- 23156721
TI  - [The role of JNK in apoptosis of renal tubular epithelial cells in diabetic rats
      with fluctuant high blood glucose].
AB  - OBJECTIVE: To explore the signal transduction mechanisms of apoptosis in renal
      tubular epithelial cells in diabetic rats with fluctuant high blood glucose.
      METHODS: Healthy SD rats were randomly divided into 3 groups: normal control
      group (A), stable high blood glucose group (B) and fluctuant high blood glucose
      group (C). Diabetic rats were induced by intraperitoneal injection of
      streptozotocin (STZ, 65 mg/kg), and the fluctuant high blood glucose animal model
      was induced by intraperitoneal injection of ordinary insulin and glucose at
      different time point every day. The superoxide dismutase (SOD) activity and the
      content of malonaldehyde (MDA) in renal tissue homogenate were detected with
      colorimetry. The protein expression of Nox4 and JNK were examined by
      immunohistochemistry and Western blot. Apoptosis was assessed by terminal
      deoxynucleotidyl transferase-mediated dUTP nick-end labelling (TUNEL). RESULTS:
      After 12 experimental weeks, significantly increased cell apoptosis, up
      regulation of Nox4 and P-JNK expression in renal tubular epithelial cells were
      observed in B and C groups compared with those in A group. The MDA content
      increased and SOD activity decreased in renal tissue in B and C groups. Above
      effects were more obviously shown in C group. CONCLUSION: Fluctuant high blood
      glucose induced more apoptosis of renal tubular epithelial cell than stable high
      blood glucose in diabetic kidney, which might be related to the activation of JNK
      signal transduction pathway.

PMID- 23156722
TI  - [Effects of progesterone on the expression of HIF-1alpha in cerebral cortex with
      hypoxic-ischemic injury in neonatal rats].

PMID- 23156723
TI  - [Research on the antioxidant effect of Enshi banqiao radix codonopsis on brain
      ischemia/reperfusion (I/R)injury].

PMID- 23156724
TI  - [Research of the mechanism for high glucose induced glomerular mesangial cell
      express TNF-alpha].

PMID- 23156725
TI  - [The attenuation of myocardial susceptibility to ischemia/reperfusion injury by
      ischemic postconditioning in hypercholesteremia rats and the role of hypoxia
      inducible factor-1alpha].
AB  - OBJECTIVE: To explore whether ischemic postconditioning can attenuate the
      myocardial injury induced by ischemia/reperfusion (I/R) in hypercholesteremic
      rats and whether hypoxia inducible factor-1alpha (HIF-1alpha) play a role in the
      protection. METHODS: Adult male Wistar rats received a high fat diet for 8 weeks
      to prepare the hypercholesteremic models. Myocardial damage induced by
      ischemia/reperfusion was evaluated by infarct size, creatine kinase (CK) activity
      and myocardial apoptosis. HIF-1alpha mRNA level was detected by real time-RT-PCR
      and the protein level was detected by Western blot. RESULTS: Myocardial infarct
      size, CK activity, and caspase-3 activity induced by I/R were markedly increased
      in hypercholesteremic rats compared with those in normal rats. Ischemic
      postconditioning attenuated the myocardial injury in both normal rats and
      hypercholesteremic rats, and increased HIF-1alpha protein level. There was a
      significant linear inverse relationship between HIF-1alpha protein level and
      infarct size (r = -0.802, P <0.01). CONCLUSION: Hypercholesteremia enhanced the
      susceptibility of myocardia to ischemia/reperfusion injury. While ischemic
      postconditioning markedly attenuated the increase of myocardial susceptibility to
      I/R induced by hypercholesteremia. HIF-1alpha might be one of the mechanisms of
      protection by ischemic postconditioning.

PMID- 23156726
TI  - [Effects of rabbit limbs ischemia/ reperfusion on myocardial necrosis and
      apoptosis].
AB  - OBJECTIVE: To investigate the effects of rabbit limbs ischemia/reperfusion on
      myocardial necrosis and apoptosis in vivo. METHODS: Thirty-six healthy new
      zealand rabbits were randomly divided into 3 groups: (1) Sham group; (2)
      I/R(Ischemia/reperfusion) group; (3) RPostC (remote postconditioning) group. The
      activity of blood serum creatine kinase (CK) and lactate dehydrogenase (LDH) were
      measured at baseline, the end of ischemia after 60 min and 120 min of reperfusion
      respectively. The extent of myocardial ischemia and the scope of myocardial
      infarction were assessed by evans blue and Triphenyl tetrazolium chloride (TTC).
      The myocardial cell's apoptosis at the area of myocardial ischemia was estimated
      by Tunel. Protein expression of caspase-3, Bcl-2 and Bax in myocardial ischemic
      area were analyzed with the method of immunohistochemistry. RESULTS: Compared
      with I/R group, the myocardial infarct size and the CK activity were
      significantly reduced in RPostC group. The Tunel positive index of RPostC group
      in ischemic myocardium was significantly lower than that in I/R group (21.79% +/-
      1.07% vs 35.81% +/- 1.10%, P < 0.05). Caspase-3 positive cells index was
      calculated with randomly selected five regions in each slide and then the
      positive cells in per hundred cells were calculated. The RPostC group of caspase
      3 positive cells was significantly lower than that in I/ R group(25.03% +/- 1.16%
      as 39% +/- 2.43%, P < 0.05). Compared with the sham group, the Bax protein
      expression index and the Bcl-2 protein expression index of I/R group and RPostC
      group were increased. The Bax/Bcl-2 ratio of RPostC group decreased, while it was
      increased in I/R. Compared with the I/R group, the Bax protein expression and
      Bax/Bcl-2 ratio of RPostC group significantly reduced, but the expression index
      of Bcl-2 ratio was significantly increased, the differences were statistically
      significant. CONCLUSION: Limbs ischemia/postconditioning could significantly
      reduce necrosis and apoptosis of ischemia/reperfusion myocardium. The mechanism
      of reducing the myocardial cell apoptosis may have relation to inhibiting the
      activation of pro-apoptotic gene caspase-3 and increased expression of Bcl-2.

PMID- 23156727
TI  - [Changes of protein kinase A expressions in central amygdaloid nuclei during the
      process of chronic morphine-induced conditioned place aversion in rats].
AB  - OBJECTIVE: To explore neurobiological mechanisms of the withdrawal-induced
      aversion. The changes of protein kinase A were measured in central amygdaloid
      nucleic (CeA) of conditioned place aversion (CPA) model rats. METHODS: (1) All 72
      male SD rats were divided into three groups, model group (MN group), and control
      group (MS group and SN group). MN group was injected with morphine,6.5 days, 10
      mg/kg, intraperitoneally (ip), twice per day, naloxone injection, 0.3 mg/kg, ip,
      along with conditioned place aversion training, to develop the CPA model. The MS
      group was administrated equivalent volume of morphine and saline. Also the SN
      group was injected with equivalent volume of saline and naloxone. (2) During the
      process of morphine-induced CPA, the expression of protein kinase A was assayed
      with immunohistochemistry in the CeA. RESULTS: In the MN group, protein kinase A
      expressions in the CeA occurred adaptive changes at different points of CPA (P <
      0.05). Protein kinase A expressions after establishment(Day7,134.43 +/- 4.481, P
      < 0.05), and after extinction (Day 13, 141.01 +/- 3.360, P < 0.01), and after
      reinstatement (Day 14,137.18 +/- 40.330, P < 0.05) were also lower than those
      before the establishment of the CPA (Day 5, 124.48 +/- 6.722). However, PKA
      expressions were not significantly different both in MS group (P > 0.05)and SN
      group (P > 0.05). CONCLUSION: (1) Protein kinase A expression, in turn regulating
      the aversion expression, in the CeA probably is a key pathway contributing to the
      development of CPA. (2) The neuroadaptation mediated by protein kinase A may be
      one of the important molecular underpinnings of CPA.

PMID- 23156728
TI  - [Effects of captopril on the protein expression of Bax and Bcl-2 in chronic
      pressure overload rats].

PMID- 23156729
TI  - [Effects of angiotensin II on the type of the skeletal muscle of amyotrophic
      rat].

PMID- 23156730
TI  - [The effect of Hsp72 on IL-6, IL-8 expression and activation of NF-kappaB in
      synoviocytes of rheumatoid arthritis].
AB  - OBJECTIVE: To investigate the effects of heat shock protein 72 (Hsp72) on the
      expression of IL-6 and IL-8 and activation of NF-kappaB in synoviocytes from
      patients suffered from rheumatoid arthritis (RA). METHODS: IL6 and IL8
      concentrations in culture supernatants were measured using enzyme-linked
      immunosorbent assays (ELISA). Nuclear translocation of NF-kappaB and degradation
      of the inhibitory protein IkappaBalpha were examined using immunohistochemistry
      and Western blot. RESULTS: Hsp72 down-regulated IL-6 and IL-8 production in RA
      synoviocytes induced by tumor necrosis factor-alpha (TNF-alpha). Hsp72 inhibited
      nuclear translocation of NF-kappaB and degradation of IkappaBalpha induced by TNF
      alpha. CONCLUSION: Hsp72 has an anti-inflammatory effect on RA by down-regulation
      of IL-6 and IL-8 in synoviocytes, which is mediated through inhibiting the
      activation of NF-KalphaB signal pathways.

PMID- 23156731
TI  - [Study of soft capsule of compound oil of jujube, arborvitae, and gardenia on
      enhancing hypoxia tolerance and anti-fatigue in mice].

PMID- 23156732
TI  - [Effect of telmisartan and pyridoxamine on oxidative stress in brain tissue of
      spontaneously hypertensive rats].
AB  - OBJECTIVE: To explore the effect of telmisartan and pyridoxamine on oxidative
      stress in brain tissue of spontaneously hypertensive rats. METHODS: Twenty-four
      spontaneously hypertensive rats were randomly divided into four groups (n = 6):
      hypertensive control group (HC group), telmisartan group (T group ), pyridoxamine
      group (P group ), telmisartan and pyridoxamine group (TP group). Wistar-Kyoto
      (WKY) rats of the same age were served as a normal control group (NC group). Drug
      treatment lasted for 16 weeks the level of hyde (MDA) in rat brain tissue, as
      well as superoxide dismutase (SOD) activity and nicotinamide adenine dinucleotide
      phosphate(NADHP) oxidase p47phox mRNA expression were observed in this study.
      RESULTS: The MDA level in brain in HC group were higher than that in NC group and
      the SOD activity were lower (P < 0.05). T group, P group and TP group had lower
      MDA level and higher SOD activity than HC group (P < 0.05). The NADPH mRNA in
      brain in HC group were significantly higher than that in NC group (P < 0.01). T
      group and TP group had decreased levels of NADPH mRNA (P < 0.01), there was no
      significant difference between HC group and P group (P > 0.05). CONCLUSION: The
      brain tissue of spontaneous hypertensive rats had been under the status of
      oxidative stress. Single application of either telmisartan or pyridoxamine could
      inhibit oxidative stress of brain tissue. However, compare with single treatment
      of telmisartan, no beneficial effects were observed in combined use of
      telmisartan and pyridoxamine.

PMID- 23156733
TI  - [Effects of CGRP on the E-cadherin expression in human bronchial epithelial
      cells].
AB  - OBJECTIVE: To discuss the effect of calcitonin gene-related peptides (CGRP) on
      epithelial cadherin (E-cd) expression in human bronchial epithelial cells (HBECs)
      in vitro. METHODS: The effect of CGRP on E-cd protein and mRNA expression in both
      normal and O3-challenged HBECs were determined by immunocytochemistry and RT-PCR.
      The signal transduction pathways of CGRP were observed by using protein kinase
      C(PKC) inhibitor (H-7), calmodulin(CaM) inhibitor (W-7) and PKA inhibitor (H-89).
      RESULTS: CGRP increased E-cd mRNA and protein expressions of normal and O3
      challenged HBECs in a dose-dependent manner. CGRP had no effect on cytoplasm E-cd
      expression. Pre-treatment with H-89, H-7 and W-7, the up-regulatory effect of
      CGRP on E-cd expression was partly abolished. CONCLUSION: CGRP increased in
      cytomembrane E-cd expression of normal and O3-challenged HBECs in a dose
      dependent manner. E-cd expression on HBECs was strengthened by CGRP via PKA, PKC
      and CaM pathways.

PMID- 23156734
TI  - [Effect of resveratrol on expression of cdk5 in activation effect of LPS on N9
      microglia cells].

PMID- 23156735
TI  - [Changes in the mRNA expression of adiponectin, adiponectin receptors, and leptin
      in adipose tissue of Wannanhua pigs at different stages of development].
AB  - OBJECTIVE: To explore the changes in the mRNA expression of adiponectin (Adp),
      adiponectin receptors(AdpR), and leptin in different adipose tissues of Wannanhua
      pigs at different stages of development, and their sexual dimorphism. METHODS:
      Five Wannanhua boars and five Wannanhua gilts were sampled at birth, 30, 45, 90,
      and 180 days of age respectively. The delta delta Ct relative quantification real
      time PCR was used to detect the transcription levels of Adp, AdpR1, AdpR2, and
      leptin mRNAs in subcutaneous (SC) and perirenal (PR) adipose tissues, and beta
      actin were used as internal standards. RESULTS: The expression level of Adp,
      AdpR1, AdpR2, and leptin mRNA in SC and PR adipose tissue were changed with age
      significantly (P < 0.01). In general, Adp mRNA expression in SC adipose tissue
      was significantly lower than that in PR adipose tissue (P < 0.05), while AdpR1,
      AdpR2, and leptin mRNA expression in SC adipose tissue were significantly higher
      than those in PR adipose tissue (P < 0.05 or P < 0.01). Although the sexual
      dimorphism were found in apart genes or apart days of age, Adp, AdpR1, AdpR2, and
      leptin mRNA expression both in SC adipose tissue and PR adipose tissue had no
      significant differences between Wannanhua gilts and boars in general. Significant
      positive correlation was found between Adp and AdpR1, AdpR2 (P < 0.05 or P <
      0.01), and significant negative correlation was found between Adp and leptin (P <
      0.05) in SC adipose tissue and PR adipose tissue respectively (P < 0.05).
      CONCLUSION: The expression of Adp, AdpR1, AdpR2, and leptin mRNA in adipose
      tissue of Wannanhua pigs followed specific developmental patterns and tissue
      specificity. Adp correlated with its receptors.

PMID- 23156736
TI  - [Effects of HiLo for two weeks on erythrocyte immune adhesion and leukocyte count
      of swimmers].
AB  - OBJECTIVE: To investigate the effects of living high-training low (HiLo) on
      innate immunity in blood of elite swimmers. METHODS: Six female swimmers
      undertook HiLo for two weeks, erythrocyte adhesion function and counts of
      leukocyte were tested in different time of training period. RESULTS: Red blood
      cell C3b receptor ring rate (RBC-C3bRR) decreased and red blood cell immune
      complex matter ring rate (RBC-ICR) increased significantly (P < 0.05), the two
      markers returned to base line 1 week after training. Counts of leukocyte and
      granulocyte decreased significantly (P < 0.05), and they recovered 1 week after
      training; Counts of lymphocyte and monocyte decreased without significance during
      training and did not recovered after training. CONCLUSION: Immunity of
      erythrocyte and granulocyte decreased quickly, but lymphocyte and monocyte
      recovered slowly, swimmers were adaptive to the training.

PMID- 23156737
TI  - [Effect of chronic unpredictable stress on conditioning fear behavior and
      somatosensory evoked potential of rats].

PMID- 23156738
TI  - [Effect of Angelica on hippocampal neurons and gliocytes of neonatal rats after
      intrauterine hypoxia].

PMID- 23156739
TI  - [The effect of advanced glycosylation end products on the expression of
      fibronectin and the regulation of protein kinase C in human peritoneal
      mesothelial cells].
AB  - OBJECTIVE: To study the effects of advanced glycosylation end products (AGEs) on
      the production of fibronectin (FN) in human peritoneal mesothelial cells (HPMC)
      in vitro and the role of protein kinase C (PKC) in this course. METHODS: The AGE
      human serum albumin (HSA) (0, 100, 500, 1 000 microg/ml) was used in culture
      medium to stimulate the HPMC. The mRNA level of FN was measured with real-time
      PCR, moreover, the protein level of FN in HPMC was detected by ELISA. With the
      method of ELISA, the PKC activities were observed. Inhibitors or activators of
      PKC were used to observe the roles of PKC pathways on the AGE-HSA stimulated
      productions of FN in HPMC. RESULTS: AGE-HSA activated PKC in HPMC in a dose, time
      dependent manner (P < 0.05). AGE-HSA up-regulated the expression of FN mRAN and
      protein in dose- and time-dependently (P < 0.01); PKC activator phorbol 12
      myristate 13-acetate (PMA) induced FN expression, respectively depletion of PKC
      and calphostin C, a PKC inhibitor, effectively prevented both PMA and AGE-HSA
      induced expression of the FN (P < 0.05). CONCLUSION: AGEs can increase the
      activities of PKC. AGEs can directly increase FN expression in HPMC which may
      contribute to peritoneal fibrosis and this is regulated by PKC.

PMID- 23156740
TI  - [Change of adhesion molecules in the lungs of rat with decompression sickness].
AB  - OBJECTIVE: To investigate the change of adhesion molecules in the lungs of rats
      suffered with decompression sickness (DCS). METHODS: Male SD rats were placed in
      the hyperbaric chamber, the chamber was compressed within 3 minutes to depths of
      7 absolute atmosphere (ATA) and held at the designated depth for 60 min, then
      rapidly decompressed (3 min) to the surface. Rats were observed for signs of DCS
      after decompression. The brains, hepatis, and lungs were removed at 30 min, 6 h,
      24 h post decompression, fixed and stained with hematoxylin eosin for routine
      histologic analysis. Lung paraffin sections were immunostained for the expression
      of intercellular adhesion molecule-1 (ICAM-1), E-selectin and major
      histocompatibility complex class II molecule (MHC-II). 2% evans blue dye in
      normal saline was injected 30 minutes prior to 6 h, 24 h before decompression.
      After 30 min, animals were perfused with 0.9% normal saline and lungs were
      harvested. Evans blue in the plasma was quantified by wavelength
      spectrophotometric analysis at 620 nm. RESULTS: Results showed that there were
      hemorrhage and edema changes in the lungs, liver and brain at 30 min post
      decompression. Compared with control animals maintained at 1 ATA, the levels of E
      selectin, ICAM-1 and MHC-II in the lungs of DCS rats were significantly increased
      post decompression. Compared with control animals, evans blue in the plasma was
      much higher at 6 h, 24 h post decompression. CONCLUSION: The bubble-induced
      adhesion molecule-mediated endothelial activation may be involved in the
      pathogenesis of DCS.

PMID- 23156741
TI  - [Study on neuroprotective effects of astragalan in rats with ischemic brain
      injury and its mechanisms].
AB  - OBJECTIVE: To study the effects of astragalan (AG) on the expression of the
      neural cell adhesion molecule(NCAM) and c-fos of hippocampus CA1 region after the
      ischemic brain injury in rats. METHODS: One hundred male Wistar rats (180-220 g)
      were divided into ten groups randomly, they were sham operated group (SOG, n =
      10), three model group(MG-ld, 3d, 7d, n = 10), as well as three low and high dose
      astragalan treatment groups (L/H-AGTG-1d, 3d, 7d, n = 10), respectively. And
      then, middle cerebral artery of MG and AGTG were intercepted by operation
      inducing brain injured. Their cerebral blood vessel were reperfused on 1, 2, 3 d,
      respectively, after the L/H-AGTG were treated with the AG (5 mg/kg and 15 mg/kg,
      ip). After neurologic impairment(NIP) was scored, animals were decapitated to
      take out hippocampus for counting apoptosis , determining the expression of the
      NCAM and c-fos by immunohistochemistry method and RT-PCR semiquantitative
      analysis, respectively. RESULTS: The NIP scores and apoptotic cell of the L-AGTG
      and H-AGTG were significantly lower than MG (P < 0.05 or P < 0.01). The
      expression of NCAM and c-fos were significantly higher than the MG (P < 0.05 or P
      < 0.01). CONCLUSION: Astragalan could improve significantly neural function of
      ischemia brain injury in rats,the mechanism concerned probably with blocking or
      reversing apoptosis of hippocampus by promoting the expression of the NCAM and c
      fos of hippocampus CA1 region.

PMID- 23156742
TI  - [Protective effect of terpenes from fructus corni on the cardiomyopathy in
      alloxan-induced diabetic mice].
AB  - OBJECTIVE: To investigate the protective effects of terpenes from fructus corni
      (TFC) on diabetic cardiomyopathy (DCM). METHODS: Diabetes was produced by a
      single injection of alloxan (220 mg/kg, i.p.) in mice. The fasting blood glucose
      of mice were tested 15 days later and that greater than 13.9 mmol/L were regarded
      as the diabetic mice which were divided randomly into the model and TFC groups.
      TFC dissolved by physiological saline (P.O, 80 mg/kg) was administrated to the
      TFC group for successive 8 weeks since the 15th day. RESULTS: Compared to the
      control group, the weight index increased significantly. The level of superoxide
      dismutase (SOD) was markedly decreased and malondialdehyde(MDA), the inflammatory
      factors (TNF-alpha, IL-6) were obviously increased in myocardium. The
      histopathological examination suggested that myocardial cells disarranged,
      swelling and the intercellular space increased in model group. It also showed the
      infiltration of inflammatory cells and fibroblasts in TFC group. The above change
      was improved significantly. CONCLUSION: TFC ameliorated the alterations of
      cardiomyopathy in diabetic mice induced by alloxan. the mechanism might be
      related to decrease blood glucose, antioxidative stress and inflammatory factors.

PMID- 23156743
TI  - [Construction and identification of the expression plasmid of SK2 (KCNN2) gene
      from human atrial myocytes with overlapping PCR].
AB  - OBJECTIVE: Small conductance calcium activated potassium channels type 2 (SK2)
      play a crucial role in atrial repolarization. It is difficult to acquire the full
      length of its coded gene KCNN2 by RT-PCR with one step. We aim to get the full
      length of KCNN2 gene and construct the plasmid by Overlapping PCR, and further
      more discuss the application of Overlapping PCR. METHODS: Total RNA was extracted
      from human right atrial tissue and cDNA was acquired with reverse transcription.
      Overlapping PCR was conducted with three pairs of primers which were designed
      according to the sequence of KCNN2 (AY258141) gene. The expression plasmid of
      pIRES-hrGFP-SK2 was constructed by directed cloning with restriction enzyme site
      and identified by enzyme cutting and sequencing. RESULTS: Three parts of PCR
      amplification were consistent with predicted size. The sequence of the plasmid
      was consistent with the gene-bank data except two sites, however, which were the
      same as gene in different tissues. CONCLUSION: The expression plasmid pIRES-hrGFP
      SK2 was constructed successfully. Overlapping PCR is a good choice for amplifying
      these genes with long size or low expression.

PMID- 23156744
TI  - [The influence of laser induced damage points on characters of the laser
      transmission].
AB  - The production and increase of damage points in optical components under high
      energy repetitive pulsed lasers is closely dependent on the effects of light beam
      intensity modulation. In the present paper, the appearance of laser-induced
      damage points on surface of K9 glass was observed. The damage is increased toward
      center. In this way, the center of the focus of laser beam is fully cracked, and
      the shell-like factures and the refractive-index changing region, which is caused
      by phase transition, are arranged outward orderly. The transmittance spectrum
      through the K9 glass and damage point were measured, indicating that the optical
      transmittances can reduce by over 20% and the declining rate is related to the
      area of damage points instead of the wavelength, which means that the full
      fracture of the material will absorb laser energy completely and is similar to
      the black body. The laser density detection with CCD shows that the damage points
      can cause the distortion of laser transmission and the scattering effect plays a
      major role. This kind of modulation effects by damage points can cause
      inhomogeneity of the laser light intensity distribution, which can induce
      diffusion of damage in optical components.

PMID- 23156745
TI  - [Research on cells ablation characters by laser plasma].
AB  - The study on the mechanism of laser ablated cells is of importance to laser
      surgery and killing harmful cells. Three radiation modes were researched on the
      ablation characteristics of onion epidermal cells under: laser direct
      irradiation, focused irradiation and the laser plasma radiation. Based on the
      thermodynamic properties of the laser irradiation, the cell temperature rise and
      phase change have been analyzed. The experiments show that the cells damage under
      direct irradiation is not obvious at all, but the focused irradiation can cause
      cells to split and moisture removal. The removal shape is circular with larger
      area and rough fracture edges. The theoretical analysis found out that the laser
      plasma effects play a key role in the laser ablation. The thermal effects,
      radiation ionization and shock waves can increase the deposition of laser pulses
      energy and impact peeling of the cells, which will greatly increase the scope and
      efficiency of cell killing and is suitable for the cell destruction.

PMID- 23156746
TI  - [Study of cuttings identification using laser-induced breakdown spectroscopy].
AB  - Cutting identification is one of the most important links in the course of
      cutting logging which is very significant in the process of oil drilling. In the
      present paper, LIBS was used for identification of four kinds of cutting samples
      coming from logging field, and then multivariate analysis was used in data
      processing. The whole spectra model and the feature model were built for cuttings
      identification using PLS-DA method. The accuracy of the whole spectra model was
      88.3%, a little more than the feature model with an accuracy of 86.7%. While in
      the aspect of data size, the variables were decreased from 24,041 to 27 by
      feature extraction, which increased the efficiency of data processing observably.
      The obtained results demonstrate that LIBS combined with chemometrics method
      could be developed as a rapid and valid approach to cutting identification and
      has great potential to be used in logging field.

PMID- 23156747
TI  - [Research on demodulation system for human body temperature measurement of
      intelligent clothing based on arrayed waveguide grating].
AB  - A system for demodulating distributed fiber Bragg grating sensors of the
      intelligent clothing was researched and realized, which is based on arrayed
      waveguide grating. The principle of demodulation method based on arrayed
      waveguide grating was analyzed, intensity--demodulating method was used to
      interrogate the wavelength of the fiber Bragg grating based on the building up of
      an experimental platform, and demodulation experiment of pre and post series of
      fiber Bragg grating was completed. The results show that the wavelength
      demodulation of the system has high linearity for fiber Bragg grating, the system
      gives a wavelength accuracy of 0.001 nm, and demodulation error caused by
      crosstalk between different sensors is 0.0005 nm. The measurement error of human
      body temperature is +/- 0.16 degrees C. It can be applied to the human body
      temperature measurement.

PMID- 23156748
TI  - [Variation of irradiance in the arctic pole during the summer].
AB  - The variation of irradiance affect the melting rate of the sea ice in the arctic
      pole, and the research on it is an important component of the global climate
      change research. The present research was based on the spectrum data collected
      during the 4th scientific research on the arctic of China in 2010, analyzed the
      variation of irradiance in the arctic pole during the summer and discussed the
      reasons for the change. This research shows that many factors lead to the change,
      among which the weather and the solar elevation angle affect the irradiance
      directly. The weather factors determine the amount of solar radiation that
      reached the ground after the absorption and attenuation of the clouds; In high
      latitude areas, there is a low solar elevation angle and the attenuation of solar
      radiation was obvious. Our research shows that the spectrum at shorter wavelength
      is more sensitive to the changes in altitude of the sun, while the impact of
      weather on the irradiance increases with wavelength. Moreover, moisture content
      in the atmosphere also affects the solar radiation reaching the ground and the
      its impact is in a particular band but not for the entire spectrum range.

PMID- 23156749
TI  - [Impact analysis of atmospheric state for target detection in hyperspectral
      radiance image].
AB  - Target detection based on hyperspectral radiance images can improve data
      processing efficiency to meet the requirements of real-time processing. However,
      the spectral radiance acquired by the remote sensor will be affected by the
      atmosphere. In the present paper, hyperspectral imaging process is simulated to
      analyze the effects of the changes in atmospheric state on target detection in
      hyperspectral radiance image. The results show that hyperspectral radiance image
      can be directly used for target detection, different atmospheric states have
      little impacts on the RXD detection, whereas the MF detection is dependent on the
      accuracy of the input spectrum, and good results can only be obtained by the MF
      detector when the atmospheric states are similar between the radiance spectrum of
      the target to be detected and the simulated hyperspectral image.

PMID- 23156750
TI  - [The solution of nonlinear function of ion mobility based on FAIMS spectrum peak
      position].
AB  - FAIMS's ion separation mechanism is based on analyte's characteristic nonlinear
      relationship between its ion mobility and applied electric field strength.
      Present characterization methods for this nonlinear relationship are based on
      precarious assumptions which incur substantial errors under many circumstances. A
      rigorous method for solving the second and fourth taylor series coefficient of
      this relationship based on dispersion voltage value (assuming half-sinusoidal
      waveform) and associated compensation voltage value of spectrum peak is
      presented, alongside with rigorous analytical functions. FAIMS spectrums were
      obtained for ethanol, metaxylene and n-butanol using custom-built FAIMS
      spectrometer, and corresponding second and fourth taylor series coefficients were
      obtained with the proposed method. Evaluation shows that this method
      substantially reduces the RMS error between interpolated and measured peak
      compensation voltage values under different dispersion voltages, confirming its
      superiority over present methods. This rigorous method would help improve
      spectral resolutions of FAIMS spectrometer, facilitating high precision FAIMS
      spectrum database construction and accurate analyte discrimination.

PMID- 23156751
TI  - [Research on the universal analytic potential function applied to diatomic
      molecules].
AB  - A new method on constructing analytical potential energy functions is presented,
      and from this a analytical potential energy function applied to both neutral
      diatomic molecules and charged diatomic molecular ions is obtained. In this
      paper, the potential energy function is examined by 21 examples of eight
      different basic kinds of diatomic molecules or ions--homonuclear ground-state for
      neutral diatomic molecule Na2-X1 sigma g+, homonuclear excitation-state for
      neutral diatomic molecule C2-A1 pi(u), homonuclear ground-state for charged
      diatomic molecular ion He2+ -X2 sigma u+, homonuclear excitation-state for
      charged diatomic molecular ion N2+ -B2 sigma(u), heteronuclear ground-state for
      neutral diatomic molecule NaLi-X1 sigma g+, heteronuclear excitation-state
      neutral diatomic molecule BH-B1 sigma+, heteronuclear ground-state for charged
      diatomic molecular ion (BC)- -X3 pi, and heteronuclear excitation-state for
      charged diatomic molecular ion (CS)+ -A2 pi etc. The theoretical values of the
      vibrational energy level of molecules calculated by the potential energy function
      are compared with RKR (Rydberg-Klein-Rees) or experimental data, and as a
      consequence, all the results are precisely consistent with RKR data.

PMID- 23156752
TI  - [Photostimulated luminescence and color centers research in BaCl(x)Br(2-x):Eu2+
      phosphors].
AB  - Eu2+ doped BaCl(x)Br(2-x), phosphors were prepared by solid state method in the
      present paper. The crystal structure and luminescent properties were studied by
      XRD, excitation, emission, and photostimulation. The XRD patterns indicate
      thatthe samples are single phase of BaCl(x)Br(2-x). The X-ray diffraction peak
      shifts to larger angle as the value of X increases. The emission spectra is a
      narrow band with a peak locating at 405 nm, which is attributed to the transition
      of 4f(6)5d-->4f(7). The excitation spectrum excited by 405 nm is a broad band
      ranging from 250-380 nm with a peak locating at 303 nm. The photostimulation
      spectrum is a broad band ranging from 480-800 nm with a peak locating at 575 nm.
      Through fitting the spectrum curve, the photostimulation spectrum is composed of
      three bands with peaks locating at about 550, 610 and 685 nm. The three fitting
      bands correspond to the three color-centers belonging to F(Cl-), F(C1-Br) and
      F(Br-) centers, respectively. The photostimulation peaks show a blue shift with
      increasing the ratio of Cl/Br.

PMID- 23156753
TI  - [Study of using regional mineral spectra library and section noise filtering to
      improve mineral identification accuracy].
AB  - Aiming at the low accuracy of mineral identification with hyperspectral data, the
      present article established regional spectra library on the basis of the study
      area geological background, and presented a pretreatment method that filters the
      original spectra by section. First, continuum based fast Fourier transform was
      used to filter the noise among 2000-2200, 2250-2300 and 2350-2500 nm. Then apply
      the rapid quantificational identification model with regional spectrum library
      was used to dispose the processed spectra. The highest effective rate of the
      result is 80%, and the highest accuracy rate is 67%. Compared with the
      identification result of original spectra, the average accuracy rate was upgraded
      by 17.7%, and the average effective rate was upgraded by 5.1%. Compared with the
      identification result of all-filtered spectra, the average accuracy rate was
      upgraded by 5.8%, while the average effective rate was upgraded by 39.8%. This
      method, which could guarantee that the identification result contains the most
      correct minerals and the fewest error ones, promoted mineral identification
      accuracy. The result with higher accuracy is significant to rapid mineral
      extraction work in field.

PMID- 23156754
TI  - [Micro-FTIR mapping tracer for the heterogeneity growth of nitrogen impurities in
      natural diamond from three localities in China].
AB  - The geographic locality determination of diamonds is of great significance in
      understanding the mantle evolution, restricting the illegal trade of conflict
      diamonds, etc. In the present article, the in-situ analysis of micro-FTIR surface
      scan technique was first applied to analyze 14 IaAB natural diamond specimens
      from China's three commercial localities. According to the FTIR spectra of
      diamonds, the nitrogen contents were calculated (1616 data points of FTIR) and
      used for mapping tracer. Th results showed that the nitrogen contents and its
      aggregation often varied in the process of diamond growth, and the nitrogen
      contents in initial nucleation stage could be higher or lower than in other
      stages. It is not an unidirectional variation for nitroge contents in different
      growth stages, indicating that the carbon and nitrogen had a complex exchange
      with mantle fluid during the diamond's crystallization course. It was regionally
      different between the diamonds from the three localities in the frequency
      distribution of nitrogen contents and NB%/N(T). Micro-FTIR mapping is more
      intuitive than the method of selecting discontinuous points, and it can trace the
      heterogeneous growth of nitrogen impurities in natural diamonds consecutively.

PMID- 23156755
TI  - [Quantitative prediction of soil salinity content with visible-near infrared
      hyper-spectra in northeast China].
AB  - Studying the spectral property of salinized soil is an important work, for it is
      the base of monitoring soil salinization by remote sense. To investigate the
      spectral property of salinized soil and the relationship between the soil
      salinity and the hyperspectral data, the field soil samples were collected in the
      region of Northeast China and then reflectance spectra were measured. The partial
      least squares regression (PLSR) model was established based on the statistical
      analysis of the soil salinity content and the reflectance of hyperspectra. The
      feasibility of soil salinity prediction by hyperspectra was decided by analyzed
      calibration model and independent validation. Models accuracy was also analyzed,
      which was established in the conditions of different treatment methods and
      different re-sampling intervals. The results showed that it was feasible to
      predict soil salinity content based on measured reflectance spectrum. The results
      also revealed that it was necessary to smooth measured hyperspectra for spectral
      prediction accuracy to be improved significantly after smoothing. The best model
      was established based on smoothed and log(l/x) transformed hyperspectra with high
      determination coefficients (R2) of 0.6677 and RPD = 1.61, which showed that this
      math transformation could eliminate noise effectively and so as to improve the
      prediction accuracy. The largest re-sampling interval is 8 nm that could meet the
      accuracy of the soil salinity prediction. Therefore, it provided scientific
      reference of monitoring soil salinization by remote sensing from satellite
      platform.

PMID- 23156756
TI  - [Transfer calibration for alcohol determination using temperature-induced
      shortwave near infrared spectra].
AB  - The authors studied the temperature influence on short-wave near-infrared spectra
      of ethanol aquatic solution and utilized four methods to establish the transfer
      partial least squares (PLS) calibration model: direct transfer calibration,
      global calibration, orthogonal signal correction (OSC) and generalized least
      squares weighting (GLSW). The PLS models were built at four temperatures: 15, 25,
      35 and 40 degrees C. The results showed that direct calibration provided high
      prediction bias: significantly high positive prediction bias for a temperature
      lower than calibration temperature and negative bias for higher temperatures. By
      using the global correction, OSC and GLSW, the systematic errors could be
      reduced. However, the global correction needed more calibration samples and built
      a more complex model. The OSC and GLSW methods provided better predictions using
      fewer latent variables. By using the GLSW method, prediction bias less than 0.1%
      and RMSEP less than 0.9% were obtained. The absolute prediction error of GLSW
      method was less than 1.5%. Additionally, the GLSW provided smaller prediction
      error at every researched temperature using fewer latent variables than OSC.
      Thus, GLSW was superior to OSC and could establish more robust transfer
      calibration model.

PMID- 23156757
TI  - [Infrared spectrum denoising with combination of lifting wavelet domain
      thresholding and median filtering].
AB  - Infrared spectra are often corrupted by noise, which may greatly influence the
      accuracy and precision of the analytical result. To improve the analytical
      precision, the authors need to denoise the spectrum data first. In the present
      paper, a spectrum denoising method by the second generation wavelet transform
      domain thresholding combined with the median filtering is introduced. The
      spectrum of a certain kind of wheat was used to test the performance of the
      proposed denoising method. In the experiment,noise with signal to noise ratio
      21.17 dB was first added to the spectrum, and then removed by the proposed
      denoising method. The signal to noise ratio (SNR), the root mean square error
      (RMSE), the average relative error of the peak value (AREPV) and the average
      error of the peak position (AEPP) were used to evaluate the performance of the
      proposed denoising method. Experimental results show that the proposed method can
      remove the spectrum noise and keep the useful information more effective than
      Donoho's soft and hard threshold method. At the same time, it can achieve a
      higher PSNR, a lower RMSE, a lower AREPV and a lower AEPP than the other two
      denoising methods.

PMID- 23156758
TI  - [Research on the combustion mechanism of asphalt and the composition of harmful
      gas based on infrared spectral analysis].
AB  - By using the Rosemount gas analyzer and the test platform of fixed bed built by
      carbon furnace, the harmful gaseous compositions and the release rules of asphalt
      and mortar under high temperature rate were analyzed quantitatively based on
      infrared spectral analysis technology. The results indicated that the combustion
      process of the asphalt and mortar can be approximately divided into two stages
      stage of primary volatile combustion, and stage of secondary volatile release
      combined with fixed carbon combustion in isothermal condition with high heating
      rate. The major gaseous products are CO2, CO, NO, NO2 and SO2. the volatile
      content is one of the key factors affecting the release rules of gaseous
      combustion products in asphalt, and reducing the volatile content in asphalt
      materials can effectively reduce the generation of gaseous combustion products,
      especially CO.

PMID- 23156759
TI  - [Nondestructive discrimination of strawberry varieties by NIR and BP-ANN].
AB  - Strawberry variety is a main factor that can influence strawberry fruit quality.
      The use of near-infrared reflectance spectroscopy was explored discriminate among
      samples of strawberry of different varieties. And the significance of difference
      among different varieties was analyzed by comparison of the chemical composition
      of the different varieties samples. The performance of models established using
      back propagation-artificial neural networks (BP-ANN), least squares-support
      vector machine and discriminant analysis were evaluated on spectra range of 4545
      9090 cm(-1). The optimal model was obtained by BP-ANN with a topology of 12-18-3,
      which correctly classified 96.68% of calibration set and 97.14% of prediction
      set. And the 94.95%, 97% and 98.29% classifications were given respectively for
      "Tianbao" (n=99), "Fengxiang" (n=100) and "Mingxing" (n=117). One-way analysis of
      variance was made for comparison of the mean values for soluble solids content
      (SSC), titratable acid (TA), pH value and SSC-TA ratio, and the statistically
      significant differences were found. Principal component analysis was performed on
      the four chemical compositions, and obvious clustering tendencies for different
      varieties were found. These results showed that NIR combined with BP-ANN can
      discriminate strawberry of different varieties effectively, and the difference in
      chemical compositions of different varieties strawberry might be a chemical
      validation for NIR results.

PMID- 23156760
TI  - [Rapid determination of fatty acids in soybean oils by transmission reflection
      near infrared spectroscopy].
AB  - In the present research, a novel method was established for determination of five
      fatty acids in soybean oil by transmission reflection-near infrared spectroscopy.
      The optimum conditions of mathematics model of five components (C16:0, C18:0,
      C18:1, C18:2 and C18:3) were studied, including the sample set selection,
      chemical value analysis, the detection methods and condition. Chemical value was
      analyzed by gas chromatography. One hundred fifty eight samples were selected,
      138 for modeling set, 10 for testing set and 10 for unknown sample set. All
      samples were placed in sample pools and scanned by transmission reflection-near
      infrared spectrum after sonicleaning for 10 minute. The 1100-2500 nm spectral
      region was analyzed. The acquisition interval was 2 nm. Modified partial least
      square method was chosen for calibration mode creating. Result demonstrated that
      the 1-VR of five fatty acids between the reference value of the modeling sample
      set and the near infrared spectrum predictive value were 0.8839, 0.5830, 0.9001,
      0.9776 and 0.9596, respectively. And the SECV of five fatty acids between the
      reference value of the modeling sample set and the near infrared spectrum
      predictive value were 0.42, 0.29, 0.83, 0.46 and 0.21, respectively. The standard
      error of the calibration (SECV) of five fatty acids between the reference value
      of testing sample set and the near infrared spectrum predictive value were 0.891,
      0.790, 0.900, 0.976 and 0.942, respectively. It was proved that the near infrared
      spectrum predictive value was linear with chemical value and the mathematical
      model established for fatty acids of soybean oil was feasible. For validation, 10
      unknown samples were selected for analysis by near infrared spectrum. The result
      demonstrated that the relative standard deviation between predict value and
      chemical value was less than 5.50%. That was to say that transmission reflection
      near infrared spectroscopy had a good veracity in analysis of fatty acids of
      soybean oil.

PMID- 23156761
TI  - [Infrared spectroscopic analysis of Guilin watermelon frost products].
AB  - The objective of the present study is to analyze different products of Guilin
      watermelon frost by Fourier transform infrared spectroscopy (FTIR), second
      derivative infrared spectroscopy and two-dimensional correlation spectroscopy (2D
      IR) under thermal perturbation. The structural information of the samples
      indicates that samples from the same factory but of different brands had some
      dissimilarities in the IR spectra, and the type and content of accessories of
      them were different compared with conventional IR spectra of samples, peaks at
      638 and 616 cm(-1) all arise from anhydrous sodium sulfate in watermelon frost
      spray and watermelon frost capsule; the characteristic absorption peaks of the
      sucrose, dextrin or other accessories can be seen clearly in the spectra of
      watermelon frost throat-clearing buccal tablets, watermelon frost throat tablets
      and watermelon frost lozenge. And the IR spectra of watermelon frost lozenge is
      very similar to the IR spectra of sucrose, so it can be easily proved that the
      content of sucrose in watermelon frost lozenge is high. In the 2D-IR correlation
      spectra, the samples presented the differences in the position, number and
      relative intensity of autopeaks and correlation peak clusters. Consequently, the
      macroscopical fingerprint characters of FTIR, second derivative infrared spectra
      and 2D-IR spectra can not only provide the information about main chemical
      constituents in medical materials, but also analyze and identify the type and
      content of accessories in Guilin watermelon frost. In conclusion, the multi-steps
      IR macro-fingerprint method is rapid, effective, visual and accurate for
      pharmaceutical research.

PMID- 23156762
TI  - [Noninvasive measurement of serum total protein content by near-infrared
      reflection spectra with tongue inspection].
AB  - The technology of tongue near-infrared reflectance spectra was used for human
      serum total protein (TP) content of noninvasive testing for the first time.
      Reflectance spectrum on the tongue tips of 58 volunteers was collected, and the
      biochemical values of serum total protein were recorded at the same time. The
      samples were separated into two parts: training set and prediction set. Two
      prediction models were established using PCA combined with BP neural network and
      PLS. Using PCA-BP model to predict the prediction set, the average relative error
      is 7.35%, RMSEP was 6.3771 g x L(-1), and the correlation coefficient was 0.9021.
      Using PLS model to predict the prediction set, the average relative error is
      4.77%, RMSEP was 0.1304 g x L(-1), and the correlation coefficient was 0.9718. It
      was approved that reflectance spectra of tongue can be used to predict TP
      accurately and noninvasively.

PMID- 23156763
TI  - [Measuring soil water content by using near infrared spectral characteristics of
      soil].
AB  - Different textured soils (sandy loam, silty clay loam and clay) from Manas
      County, Xinjiang were researched with indoor spectral reflectance, continuum
      removal was used to process soil spectra curve, and correlation analysis was made
      about normalized spectral reflectance and water content for modeling. The results
      show that different textured soils have reflectance in a order that clay>silty
      clay loam>sandy loam; the critical points of field capacity in sandy loam, silty
      clay loam and clay were 20.01%, 24.10% and 30.43% respectively, and water content
      was inversely proportional to spectral reflectance below such critical points
      while proportional above the points. Within 1390-1623 nm band, the negative
      correlation coefficients of soil water content and normalized spectra reflectance
      show better negative correlation and reaching significant levels, R2 of the model
      established for soil water content prediction exceeded mostly 0.8, and the
      average relative error of the model was 10%. The model could accurately reflect
      the soil moisture content, Its advantages such as accuracy, non-destruction and
      rapidness provide a new approach to measuring soil water content.

PMID- 23156764
TI  - [Sugar characterization of mini-watermelon and rapid sugar determination by near
      infrared diffuse reflectance spectroscopy].
AB  - In the present paper, the distribution of sugar level within the mini-watermelon
      was studied, a new sugar characterization method of mini-watermelon using average
      sugar level, the highest sugar level and the lowest sugar level index is
      proposed. Feasibility of nondestructive determination of mini-watermenlon sugar
      level using diffuse reflectance spectroscopy information was investigated by an
      experiment. PLS models for measuring the 3 sugar levels were established. The
      results obtained by near infrared spectroscopy agreed with that of the new method
      established above.

PMID- 23156765
TI  - [Study on rapid non-destructive detection of the freshness of paddy based on
      NIRS].
AB  - A prediction model of paddy storage time was established based on near infrared
      reflectance (NIRS) and chemometrics. A spectroradiometer was used for collecting
      spectra in the wavelength range from 950 to 1 650 nm. The NIR spectra were
      collected from 90 samples of paddy. The best pretreatment method was obtained
      while choosing the total spectra area combined with PLS using the UNSCRAMBLER
      9.7. The best pretreatment method is first derivative combined with S. Golay, and
      the number of principal components is 7. The model is feasible, because the r2 is
      0.9679, RMSEP is 54.51 and the result of T-test is passable while validation
      method is cross validation In this paper, a feasible method is established to
      measure the storage time of paddy based on near infrared reflectance(NIRS)and
      chemometrics.

PMID- 23156766
TI  - [Similar spectrum of infrared spectrum and its application in identification of
      Chinese herbs].
AB  - In the present paper, the similar spectra of 18 samples, which include
      Astragalus, red-blue Astragalus and Codonopsis, were obtained in the range of
      1600-700 cm(-1). The result showed that all kinds of herbs have their own
      characteristic similar spectra, and 18 samples can be identified according to the
      characteristic similar spectra. Furthermore, three correlation coefficients of 93
      ganoderma samples were calculated which is in the range of 1560-1502, 1460-1421
      and 1319-1260 cm(-1) according to the information of similar spectrum of infrared
      spectrum of ganoderma. Without priori knowledge of the classification of these
      samples, the K-means cluster analysis can successfully divide them into four
      classes, i.e., Ganoderma lucidum and Ganoderma sinensis, Ganoderma atrum,
      Ganoderma aoshiba, Ganoderma multiplicatum. This result is consistent with the
      result of morphological classification.

PMID- 23156768
TI  - [Raman spectroscopic investigation of hydrogen storage in nitrogen gas hydrates].
AB  - Recently, hydrogen storage using clathrate hydrate as a medium has become a
      hotspot of hydrogen storage research In the present paper, the laser Raman
      spectroscopy was used to study the hydrogen storage in nitrogen hydrate. The
      synthetic nitrogen hydrate was reacted with hydrogen gas under relatively mild
      conditions (e.g., 15 MPa, -18 degrees C). The Raman spectra of the reaction
      products show that the hydrogen molecules have enclathrated the cavities of the
      nitrogen hydrate, with multiple hydrogen cage occupancies in the clathrate
      cavities. The reaction time is an important factor affecting the hydrogen storage
      in nitrogen hydrate. The experimental results suggest that nitrogen hydrates are
      expected to be an effective media for hydrogen storage.

PMID- 23156767
TI  - [Study on rapid quantitative analysis of the active ingredient in ABC
      extinguishing agent and type identification of extinguishing agent powders using
      near infrared spectroscopy].
AB  - A new quantitative method to determine the NH4H2PO4 in ABC powder extinguishing
      agent and to distinguish between ABC and BC powder extinguishing agents using
      near infrared diffuse reflectance spectroscopy is proposed. A PLS calibration
      model for the NH4H2PO4 content in extinguishing agent powder was established,
      with RMSECV = 2.1, RMSEP = 2.4. An identification model for ABC and BC powder
      extinguishing agents was built by SIMCA and the identification accuracy rate is
      100%. This method, compared to the present standard method, has the
      characteristics of rapidness and easy operation, whichis fit for the quantitative
      analysis and type distinguishing of the fire products on site.

PMID- 23156769
TI  - [Infrared and Raman spectra study on Tianhuang].
AB  - The Tianhuang stones, from Shoushan in China, were studied by using X-ray powder
      diffractometry (XRD), infrared (IR) spectroscopy and Raman spectroscopy to obtain
      the spectra characterization. Wave numbers 3621, 3629 and 3631 cm(-1) in the IR
      spectra and 3626, 3627 and 3632 cm(-1) in the Raman spectra are the
      characteristic peaks of dickitic Tianhuang, nacritic Tianhuang and illitic
      Tianhuang, respectively. Raman spectra assigned to OH are in good agreement with
      the IR results at 3550 -3750 cm(-1). Dickitic Tianhuang includes ordered dickite
      and disordered dickite. Compared with ordered dickite, the band assigned to OH3
      of disordered dickite shifts to low-frequency by 8 cm(-1) and the relative
      intensity becomes stronger. The disorder structure may relate to the high level
      of Fe. The IR absorption spectra of nacritic Tianhuang superimposes strong peaks
      of dickite, indicating that IR absorption bands of dickite are stronger than that
      of nacrite at 3550-3750 cm(-1). The main mineral composition of illitic Tianhuang
      is 2M(1), while illite Tianhuang contains a small amount of 1M. All these
      characters provide a theoretical basis for the scientific identification of
      Tianhuang.

PMID- 23156771
TI  - [Raman spectroscopy analysis of carbon structural evolution of diesel particulate
      matters with the treatment of nonthermal plasma].
AB  - Original and nonthermal plasma treated particulate matters (PM) samples of a
      diesel were obtained and characterized by Raman spectroscopy. A five-bands model
      was adopted for Raman spectrum curve fitting. As parameters involving most
      information about carbon structure, variation of FWHM of D1 band and D3 relative
      intensity were analyzed. It was found that original PM presented higher graphical
      structural order and lower chemical heterogeneity with the increase in the diesel
      load. After the treatment of NTP, the graphical structural order and chemical
      heterogeneity of PM kept at a relative stable level, affected very slightly by
      diesel load. Meanwhile, the amount of molecular carbon in PM increased. Further
      study for relation between structural evolution and chemical reactivity of PM
      with chemical kinetics would make Raman spectroscopy of great promise to become
      an important method for PM characterization, which could provide basis for more
      effective removal.

PMID- 23156770
TI  - [Self-assembled film of gold nanoparticles at a air/water interface used as a
      SERS substrate to detect melamine].
AB  - Self-assembled monolayer film of gold nanoparticles (55 nm) was formed at air
      water interface by the driving force of wettability-shift of gold nanoparticles
      from hydrophilic property to hydrophobic property when encapsulated with 1
      dodecanethiol. SEM image shows that the structure of the surface is nearly
      monolayer with closed arrays of uniform particle size when the film is
      transferred onto Si wafer. The substrate can be used for SERS substrate to
      realize semiquantitative analysis of melamine and the detection limit can reach l
      x 10(-9) g x L(-1). This SERS substrate is of wide application, not only for
      melamine but also for nonpolar molecule such as polycyclic aromatic hydrocarbons.

PMID- 23156772
TI  - [Curve fitting based on genetic algorithms for quantitative resolution in
      overlapped fluorescence spectra].
AB  - The exponentially modified Gaussian (EMG) model-based genetic algorithm was used
      as a fitness function for fitting fluorescence spectrogram. The method was
      effective for solving the interference of fluorescent substance in the course of
      the multi-component quantitative analysis. As an example, the interference of
      endogenous fluorophores in different urines with the fluorescence of gatifloxacin
      (GFLX) was examined. A good eradicating efficacy was achieved by using the
      fitting fluorescence spectrogram. Under the optimized experimental conditions,
      the good linear relationship between the fluorescence intensity and GFLX
      concentration was obtained in the range of 0.06-3.5 microg x mL(-1) with a
      correlation coefficient of 0.9994. The detection limit and recovery were 0.02
      microg x mL(-1) and 99.2%-109.4%, respectively, with the relative standard
      deviation from 1.3% to 2.7%. The proposed fitting fluorescence spectrometric
      method was rapid, simple and highly sensitive for the determination of GFLX in
      different human urine without preseparation. The recovery, selectivity,
      linearity, precision and accuracy of the method are convenient for routine assays
      and pharmacokinetic studies.

PMID- 23156773
TI  - [Effects of PEMF on fluorescence spectra of rats serum].
AB  - To investigate the relationship between the fluorescence spectra of serum and the
      brain injury effect, the alteration of fluorescence emission in serum was
      collected by fluotescence spectroscopy, the pathologic changes in the rat brain
      were obvious by histopathology after exposure to PEMF. Sprague-Dawley male rats
      were randomized into sham exposed and PEMFs exposed groups. After exposure to
      PEMF (3.5 ns rising time, 14 ns pulse width, and amplitude up to 200 kV/400 kV at
      1 Hz repetitive rate) at 0.5, 1, 3, 6 and 12 h, the expression of S100B and the
      fluorescence spectra in serum were detected, the changes in brain morphology were
      observed. The results showed that the fluorescence intensity of 400 kV groups
      were higher than 200 kV groups at different time points after exposure to PEMF.
      It suggests that the extent of brain injury was associated with the pulse
      frequency. The trends of fluorescence spectra in serum coincide with the
      expression of S100B and pathologic changes. It shows that fluorescence
      spectroscopy could apply to analysis of the effect of brain injury after exposure
      to PEMF.

PMID- 23156774
TI  - [Interaction between latex microspheres and antibody proteins revealed by
      fluorescence spectroscopy].
AB  - Latex-antibody complexes were prepared by the method of covalent coupling and the
      properties of the complexes were studied by fluorescence spectrophotometric
      method for the purpose of revealing the interaction between latex microspheres
      and antibody proteins. Analysis of intrinsic fluorescence spectra showed that
      after being coupled with latex microspheres, the emission maximum of antibody
      protein showed an obvious blue shift, the intensity of emission maximum decreased
      significantly, the tertiary structure of antibody protein changed to some extent,
      the interaction between latex microspheres and antibody proteins had a great
      quenching effect on the intrinsic fluorescence spectra of antibody proteins, the
      quenching effect was enhanced along with the increasing pH value and latex
      concentration, and the quenching mechanism was static quenching. Results of
      exogenous fluorescence spectra showed that the fluorescence intensity of emission
      maximum was enhanced significantly after being coupled with latex microspheres,
      the hydrophobicity of antibody protein was decreasing with the increase in the pH
      values, however, due to the increasing latex concentration, the hydrophobicity
      antibody protein was increasing.

PMID- 23156775
TI  - [Studies on micelle behaviors of sophorolipid biosurfactant by steady-state
      fluorescence probe method].
AB  - The critical micelle concentration (CMC) of sophorolipid was determined by steady
      state fluorescence probe method in which pyrene was used as fluorescence probe.
      Meanwhile, the changes in the sophorolipid CMC were examined in the addition of
      NaCl and aliphatic alcohol, respectively. The results showed that the CMC of
      sophorolipid was 1.3 x 10(-4) mol x L(-1) and had a slight decrease as NaCl
      concentration increased. However, the CMC of sophorolipid appeared to increase in
      the presence of aliphatic alcohol. The aggregation numbers and the micelle size
      of sophorolipid solution were investigated by fluorescence quenching and laser
      light scattering method. The aggregation numbers were 4-8 with the concentrations
      of sophorolipid in the range of 4 -8 CMC and the micelle mean diameter for
      sophorolipid with the concentration of 6 CMC was about 90 nm. These experimental
      results indicated that the micelle should be incompact.

PMID- 23156776
TI  - [Ultraviolet absorption spectrum analysis and identification of medicinal plants
      of Paris].
AB  - Species of Paris are important medicinal plants of China. They possess
      anticancer, hot alexipharmic, detumescence, acesodyne, and arrest blood and
      remove blood stasis effects. They are the main raw material for several Chinese
      patent drugs such as "Yunnan Baiyao", "Gong Xue Ning", "Re Du Qing" and "Ji De
      Sheng Sheyaopian". The present paper, through optimizing the chloroform, absolute
      ethyl alcohol and water extraction condition of Paris by orthogonal test L3(4)
      (16), using mean value, smoothness and second differential methods on the
      observed UV spectrum, to inspects the RSD of stability and repeatability of
      different waveband. By SIMCA and the common and variant peak ratio dual index
      sequence analysis method, it evaluated the quality and quantity of Paris. The
      results showed that at the time of 50, 40 and 50 min, chloroform, absolute ethyl
      alcohol and water had the highest extraction ratios. Within 20 h, the RSDs of
      stability were 0.06-1.88, 0.05-2.42 and 0.03-0.35; the RSDs of accuracy were 0
      1.48, 0.05-0.37 and 0.09-0.44; and the RSDs of repeatability were 0-1.23, 0.04
      0.30 and 0.12-0.25 respectively. The qualitative analysis revealed large
      differences between different Paris species and different areas. The quantitative
      analysis indicated that the highest common peak ratio among the Paris samples was
      80.00% and the lowest variant peak ratio was 6.25%. The method evaluated Paris of
      different species and from different producing areas, and also quantitatively
      assessed the arbitrary two samples, clarified the similarity between the species
      and areas of Paris, which provided basis of distinguishing the real and false,
      identification of variety and quality evaluation for Chinese herbal medicine.

PMID- 23156777
TI  - [Study on the mechanism of liesegang pattern development during carbonating of
      traditional sticky rice-lime mortar].
AB  - Liesegang patterns in traditional sticky rice-lime mortar undergoing carbonation
      were investigated by means of FTIR, XRD and SEM. Results indicate that well
      developed Liesegang patterns only occur in the mortar prepared with aged lime and
      sticky rice. The smaller Ca(OH)2 particle size in aged lime and the control of
      the sticky rice for the crystallization of calcium carbonate lead to the small
      pores in this mortar. These small pores can make Ca2+ and CO3(2-) highly
      supersaturated, which explains the reason why Liesegang pattern developed in the
      sticky rice-aged lime mortar. The formed metastable aragonite proves that
      Liesegang pattern could be explained based on the post-nucleation theory.

PMID- 23156778
TI  - [Study on a method for fast selecting feature wavelengths from the spectral
      information of crop nitrogen].
AB  - Research on a method for fast selecting feature wavelengths from the nitrogen
      spectral information is necessary, which can determine the nitrogen content of
      crops. Based on the uniformity of uniform design, the present paper proposed an
      improved particle swarm optimization (PSO) method. The method can choose the
      initial particle swarm uniformly and describe the optimization space well by
      fewer sample points, which is helpful to avoiding the local optimum and
      accelerate the convergence. Then, the method was applied to fast select the
      nitrogen spectral wavelengths of soybean, cotton and maize. Calibration models
      based on the partial least square (PLS) method and selected wavelengths were
      constructed. The results illustrate that compared with the original wavelengths,
      the number of selected wavelengths decreases about 93%, which means the
      computation is simplified. Also, the precision of PLS prediction mode based on
      the selected wavelengths improves by 34% at least, and the prediction ability of
      calibration model increases greatly. Therefore, the proposed method is both
      correct and effective.

PMID- 23156779
TI  - [Study of spectrum drifting of primary colors and its impact on color rendering
      properties].
AB  - LEDs are currently used widely to display text, graphics and images in large
      screens. With red, green and blue LEDs as three primary colors, color rendition
      will be realized through color mixing. However, LEDs' spectrum will produce
      drifts with the changes in the temperature environment. With the changes in the
      driving current simulating changes in the temperature, the three primary color
      LEDs' spectral drifts were tested, and the drift characteristics of the three
      primary colors were obtained respectively. Based on the typical characteristics
      of the LEDs and the differences between LEDs with different colors in composition
      and molecular structure, the paper analyzed the reason for the spectrum drifts
      and the drift characteristics of different color LEDs, and proposed the equations
      of spectrum drifts. Putting the experimental data into the spectrum drift
      equations, the paper analyzed the impacts of primary colors on the mixed color,
      pointed out a way to reduce the chromatic aberration, and provided the theory for
      engineering application of color LEDs.

PMID- 23156780
TI  - [Improving component analysis ability of the complex mixed solutions by multi
      dimensional diffuse transmittance spectrometry].
AB  - The multi-dimensional diffuse transmittance spectrums were collected by the
      traditional near-infrared transmittance method combined with a scanning device,
      and then used for component analysis of the complex mixed solution. A xenon
      light, an electric control translation stage and a spectrometer were gathered to
      set up a device; Intralipid-20%, India-ink and C6H12O6 were used to prepare 225
      kinds of complex mixed solutions; the diffuse transmittance spectrums were
      measured at 20 points off the transmission center distributed from 0-5 mm
      (interval 0.25 mm); the single and multi-point diffuse transmittance spectrums
      were analyzed by partial least squares regression for modeling and prediction.
      The results show that the modeling and prediction accuracy of the concentrations
      of the intralipid-20% and India-ink increased with the growing of the
      transmittance points, but the concentration of the C6H12O6 did not increase. It
      is proved that the spectrums collected by different points can raise the signal
      to noise radio of the strong absorption and scattering substance, and the signal
      to noise radio of the weak absorption and scattering substance would be improved
      by increasing the current system accuracy.

PMID- 23156781
TI  - [Study of residue preservatives thiabendazole, o-phenylphenol and diphenyl in
      fruits and vegetables by SPE-separation technology].
AB  - The residue of thiabendazole, o-phenylphenol and diphenyl in vegetables and
      fruits was detected by solid-phase extraction and ultraviolet-spectrophotometry.
      Samples were extracted under basic conditions with petroleum ether: ethyl acetate
      (2:1). The analytes were first enriched, purified and separated through a C18
      solid-phase extraction column. Thiabendazole, o-phenylphenol and diphenyl in the
      C18 solid-phase extraction column were eluted with 30% ethanol-acid solution (pH
      2.5), 55% methanol -alkaline solution (pH 11.5) and 75% ethanol-acid solution (pH
      2.5) respectively ,then detected by ultraviolet-spectrophotometry. The linear
      ranges were from 1 to 10 microg x mL(-1) with a good linear relationship (r >
      0.9998) for thiabendazole, o-phenylphenol and diphenyl. The recovery range was
      from 72.1% to 103.5%, with the relative standard deviations between 1.2% and
      7.7%. The limit of detection (S/N = 3) was 0.09 Mg x mL(-1) (TBZ), 0.5 microg x
      mL(-1) (OPP) and 0.1 microg x mL(-1) (DP). The method was successfully applied to
      residues of preservatives in fruits and vegetables. These results indicated that
      this method is simple, rapid and sensitive for the simultaneous determination
      requirements of residues in vegetables and fruits.

PMID- 23156782
TI  - [Cool/Hot target effect of the water fog infrared stealth].
AB  - Artificial spray fog will come into being cool target because of the strong
      evaporation and convection but weak radiation heat flux, when it is used for
      defence of infrared imaging guided missile. Also, when it is the contrary
      condition, the water fog will come into being hot target. In order to open out
      the phenomenon particularly, a math model which can account for the cool/hot
      effect produced by water fog shielding the thermal radiation is established by
      coupling the calculation of radiation transfer equation and energy conversation
      equation, based on the Mie theory. This model is proved to be accurate in
      comparison with the Monte-Carlo method and Lambert-Beer' law. The water fog is
      seemed as absorbing, emitting and anisotropic scattering medium, and the medium
      radiation, multiple scattering, target radiation flux, and environment influence
      such as the conductivity, convection turbulent heat diffusion and evaporation is
      calculated. The phenomenon of cool/hot target effect can be shown in detail with
      this model.

PMID- 23156783
TI  - [Preparation and characterization of modified kaolins and their photocatalytic
      property].
AB  - In order to develop the cheap and efficient photocatalysts, kaolins were modified
      through calcination and acid leaching. In succession, the prepared samples were
      characterized using thermal gravimetric-differential thermal analysis (TG-DTA),
      scanning electron microscope (SEM) coupled with energy dispersive spectroscopy
      (EDS), X-ray diffraction (XRD), ultraviolet-visible spectroscopy (UV-Vis) and BET
      specific surface area measurements (BET). Methyl orange, used as a model
      reactant, was degraded under UV light irradiation to evaluate the photocatalytic
      activities of the prepared samples. From UV-Vis spectroscopy analyses, an obvious
      increase in the red shift of the absorption edge was observed for the samples
      treated with acid. The acid sites generated during the modification of kaolin
      were determined through adsorbed pyridine analysis using infrared spectroscopy
      (Py-IR). Kaolins modified using over 30% H2SO4 contained both Bronsted and Lewis
      acid sites. Combining the results of photocatalytic experiment with the
      conclusions of Py-IR and XRD, the acid properties of the prepared samples were
      the main factors that affected their catalytic activity.

PMID- 23156784
TI  - [Research on spectral response of CdSe quantum dots dopted polymer solar cell].
AB  - In the present paper, bulk heterojunction polymer solar cells based on P3HT:PCBM
      and P3HT:PCBM:QDs active layer were fabricated and measured respectively. The
      experimental result showed that the addition of QDs can broaden the spectral
      response and enhance photoinduced electron transfer. The conversion efficiency of
      device with QDs is about 25% higher than that without QDs.

PMID- 23156785
TI  - [MTCARI: A kind of vegetation index monitoring vegetation leaf chlorophyll
      content based on hyperspectral remote sensing].
AB  - The chlorophyll content of plant has relative correlation with photosynthetic
      capacity and growth levels of plant. It affects the plant canopy spectra, so the
      authors can use hyperspectral remote sensing to monitor chlorophyll content. By
      analyzing existing mature vegetation index model, the present research pointed
      out that the TCARI model has deficiencies, and then tried to improve the model.
      Then using the PROSPECT+SAIL model to simulate the canopy spectral under
      different levels of chlorophyll content and leaf area index (LAI), the related
      constant factor has been calculated. The research finally got modified
      transformed chlorophyll absorption ratio index (MTCARI). And then this research
      used optimized soil background adjust index (OSAVI) to improve the model. Using
      the measured data for test and verification, the model has good reliability.

PMID- 23156786
TI  - [Geometric distortion correction for hyperspectral image using a rotating scan
      reflector].
AB  - Offner imaging spectrometer is a kind of pushbroom imaging system. Hyperspectral
      images acquired by Offner imaging spectrometers require relative motion of sensor
      and scene that is translation or rotation. Via rotating scan with a reflector at
      the front of sensor's len, large objects can be entirely captured. But for the
      changes in object distances, geometric distortion occurs. A formula of space
      projection from an object point to an image point by one capture was derived.
      According to the projection relation and slit's motion curve, the object points'
      coordinates on a reference plan were obtained with rotation angle for a variable.
      A rotating scan device using a reflector was designed and installed on an Offner
      imaging spectrometer. Clear images were achieved from the processing of
      correction algorithm.

PMID- 23156787
TI  - [Detection of activity of POD in tomato leaves based on hyperspectral imaging
      technology].
AB  - Activities of POD in tomato leaves were measured rapidly using hyperspectral
      imaging technology combined with chemometrics method. Operation process was:
      extracting spectra curve, pretreatment of spectra data, extracting characteristic
      wavelengths with SPA, and establishing prediction model for determining POD
      activities. In comparison with other methods such as SG, SNV, MSC, 1-Der and 2
      Der, DOSC was the optimal pretreatment. It was shown in this research that SPA
      PLS model was the optimal effective model among all models (SPA-MLR, SPA-PLS, SPA
      BPNN and SPA-LS-SVM) for forecasting POD activities. The model was based on
      reflectance information of effective wavelengths (443, 464, 413, 410, 401, 402,
      426 and 926 nm) extracted by SPA. Rp and RMSEP were 0.9353 and 37.80 U x g(-1),
      respectively. The result indicated that it was feasible to determine the POD
      activities with hyperspectral imaging technology, and the prediction accuracy of
      model was satisfactory. It was a new method for dynamic observation of POD
      activities and growth state of tomato.

PMID- 23156788
TI  - [Research of heavy metals determination in cereals by inductively coupled plasma
      mass spectrometry].
AB  - The present paper established the determination method of heavy metals such as
      As, Pb, Hg and Cd in cereals by inductively coupled plasma mass spectrometry (ICP
      MS) with microwave digestion. The pretreatment conditions were improved and the
      instrument operating parameters were optimized. 72Ge, 115In and 209Bi were
      selected as the internal standard elements to overcome the matrix effects and
      instrument fluctuations effectively. Interference correction equations were used
      to eliminate the interference of polyatomic ions. Satisfactory linearity of
      standard curves was obtained with elemental correlation coefficients over 0.9999.
      The detection limits were in the range of 0.0006-0.016 mg x L(-1), the recoveries
      of samples were 90%-110%, and the RSD was within 5%. The accuracy of the method
      was evaluated with national standard reference materials and the interference
      test was experimented using standard solution. Studies have shown that the method
      is suitable for rapid determination of heavy metals As, Pb, Hg and Cd in cereals
      with wide linear range, good precision and high accuracy.

PMID- 23156789
TI  - [Variation in soil Mn fractions as affected by long-term manure amendment using
      atomic absorption spectrophotometer in a typical grassland of inner Mongolia].
AB  - The effect of sheep manure amendment on soil manganese fractions was conducted in
      a 11 year experiment at inner Mongolia grassland, using sequential extraction
      procedure in modified Community Bureau of Reference, and determined by atomic
      absorption spectrophotometer. Five treatments with dry sheep manure addition rate
      0, 50, 250, 750, and 1500 g x m(-2) x yr(-1), respectively, were carried out in
      this experiment. Results showed that the recovery rate for total Mn was 91.4%
      105.9%, as the percentage recovered from the summation of the improved BCR
      results with aqua regia extractable contents, and it was 97.2%-102.9% from
      certified soil reference materials. Plant available exchangeable Mn could be
      enhanced by 47.89%, but reducible and total Mn contents decreased significantly
      under heavy application of manure at depth of 0-5 cm. The effect of manure
      amendment on Mn fractions was greater in 0-5 cm than in 5-10 cm soil layer. The
      results are benefit to micronutrient fractions determination and nutrient
      management in grassland soils.

PMID- 23156790
TI  - [Determination of soil exchangeable base cations by using atomic absorption
      spectrophotometer and extraction with ammonium acetate].
AB  - A method to determine soil exchangeable calcium (Ca), magnesium (Mg), potassium
      (K), and sodium (Na) by using atomic absorption spectrophotometer (AAS) and
      extraction with ammonium acetate was developed. Results showed that the accuracy
      of exchangeable base cation data with AAS method fits well with the national
      standard referential soil data. The relative errors for parallel samples of
      exchangeable Ca and Mg with 66 pair samples ranged from 0.02%-3.14% and 0.06%
      4.06%, and averaged to be 1.22% and 1.25%, respectively. The relative errors for
      exchangeable K and Na with AAS and flame photometer (FP) ranged from 0.06%-8.39%
      and 0.06-1.54, and averaged to be 3.72% and 0.56%, respectively. A case study
      showed that the determination method for exchangeable base cations by using AAS
      was proven to be reliable and trustable, which could reflect the real situation
      of soil cation exchange properties in farmlands.

PMID- 23156791
TI  - [Infrared spectroscopy and XRD studies of coral fossils].
AB  - Coral fossil is an old remain of multicellular animal on the earth, and formed by
      various geological processes. The structural characteristics and compositions of
      the coral fossils with different color and radial texture on the surface were
      studied by infrared absorption spectroscopy and X-ray powder diffraction
      analyses. The results show that the studied coral fossils mainly are composed of
      SiO2, and the radial microstructure characterized by the calcareous coral cross
      section is preserved. It is formed by metasomatism by SiO2. The infrared
      absorption spectra of the coral fossil with different color and texture are
      essentially the same, showing typical infrared absorption spectra of the quartz
      jade. XRD analysis shows that the main components of the coral fossils with
      different color and texture are consistent and mainly composed of SiO2 with a
      trace amount of other minerals and without CaCO3.

PMID- 23156792
TI  - [Determination of 16 elements in the different pine pollen by TXRF].
AB  - After microwave digestion, 16 elements in pine pollen were simultaneously
      determined by TXRF. The results show that all the 16 elements were found in all
      pine pollens. There was a significant difference in the average content of the
      element such as Ca, Ti, Mn, Zn and Rb between different groups of pine pollen (P
      < or = 0.01). There was a difference in the average content of the element such
      as K, V, Fe, Co, Cu and Sr between them (P < or = 0.05). And there was no
      difference in the average content of the element such as Cr, Ni, As, Pb and Se
      between them. The results also show that pine pollen has the spectral
      characteristics of warm property or cold property drug. They were closely related
      to the tree species and the growth environment or the growth area.

PMID- 23156793
TI  - [Chemical composition and chromaticity characteristic of Jilan glaze of Ming and
      Qing official kilns].
AB  - Color glazes of Ming and Qing official kilns are excellent representatives of the
      famous ancient Chinese porcelains. The study of official ware with Jilan glaze
      has been an important topic. But it made slow progress due to the rarity of
      samples with strict production management and using system. The recipes, chemical
      composition and chromaticity characteristic of the Jilan samples excavated from
      official kilns in the Ming and Qing dynasties were first discussed by
      systematical testing with the energy dispersive X-ray fluorescence (EDXRF) and
      color difference meter. The results showed that the porcelain stone content in
      Jilan bodies of official kiln in the Ming dynasty is higher than the samples of
      the Qing dynasty. The manganese content in Jilan glazes of the Ming dynasty is
      higher than that in the Qing dynasty, while the glaze ash addition and the
      lightness value in the glaze are opposite.

PMID- 23156794
TI  - [An automated method to fit stellar continuum based on statistic windows].
AB  - A novel statistic window based method to fit stellar continuum is proposed. First
      a stellar spectrum is divided into a series of statistic windows in which a
      certain percent of flux points is selected according to S/N ratio; then low order
      polynomial iteration fitting is carried out based on the selected flux points to
      obtain the stellar continuum. Experimental results show that the continuum
      obtained by the proposed method is more close to the real continuum, compared to
      other existed methods. This method has a better practical applicability and
      robustness to all kinds of spectra (except M-type spectrum) in SDSS. It also
      works well for Guoshoujing Telescope (LAMOST) pilot survey spectra.

PMID- 23156795
TI  - [Lossless compression of hyperspectral image for space-borne application].
AB  - In order to resolve the difficulty in hardware implementation, lower compression
      ratio and time consuming for the whole hyperspectral image lossless compression
      algorithm based on the prediction, transform, vector quantization and their
      combination, a hyperspectral image lossless compression algorithm for space-borne
      application was proposed in the present paper. Firstly, intra-band prediction is
      used only for the first image along the spectral line using a median predictor.
      And inter- band prediction is applied to other band images. A two-step and
      bidirectional prediction algorithm is proposed for the inter-band prediction. In
      the first step prediction, a bidirectional and second order predictor proposed is
      used to obtain a prediction reference value. And a improved LUT prediction
      algorithm proposed is used to obtain four values of LUT prediction. Then the
      final prediction is obtained through comparison between them and the prediction
      reference. Finally, the verification experiments for the compression algorithm
      proposed using compression system test equipment of XX-X space hyperspectral
      camera were carried out. The experiment results showed that compression system
      can be fast and stable work. The average compression ratio reached 3.05 bpp.
      Compared with traditional approaches, the proposed method could improve the
      average compression ratio by 0.14-2.94 bpp. They effectively improve the lossless
      compression ratio and solve the difficulty of hardware implementation of the
      whole wavelet-based compression scheme.

PMID- 23156796
TI  - [EUV flat field grating spectrometer and performance measurement].
AB  - A high-resolution extreme ultraviolet (EUV) spectrometer has been developed to
      diagnose the magnetically confined plasmas. A holographic spherical varied line
      spacing concave grating which provides a flat focal plane is used as the
      diffraction element working with the grazing incidence angle of 3 degrees. The
      nominal groove density is 1200 lines x mm(-1). A deeply cooled back-illuminated
      CCD camera is used as the spectra detector and a mechanical shutter is used to
      control the time of exposure. It covers the wavelength range of 5-50 nm with the
      CCD cameral moving along the spectra focal plane to cover different wavelength
      range interested. Spectrometer design is presented and it was tested by a Penning
      discharge light source. By the wavelength calibration, the actual parameters of
      the optical system were calculated and the wavelength accuracy is 0.003 nm.
      Results show that the spectral resolution is about 0.015 nm at 20 nm with the
      width of entrance slit opened at 30 microm, which agrees with the design goal.

PMID- 23156797
TI  - [Design and implementation of real-time processing platform for movement error
      correction of hyperspectrual imaging].
AB  - The approach that deals with compressed and packed image data transmitted from
      satellite to the ground is too slow for real-time application occasion, it also
      has huge image, multi-processing step and complexity recovery arithmetic
      synchronously, so it is urgent to build accurate and fast data processing
      platform for real-time processing. For the moment, the platform for data recovery
      and error correction is much less, the so-called successful platform may directly
      affect the effect of target detection and identification because of processing
      speed, precision, flexibility, configuration and upgrade. The platform we build
      is to set spatial modulation spectrometer as the research goal, We design and
      implement a hardware platform based on Xilinx Virtex-5 FPGA, It is combined with
      ISE IP soft-core resources which is configurable, high-precision and flexible by
      focusing on analyzing key aspects of the hardware platform. And the relevant test
      data were drawn, then a good way for spectrum recovery and error correction was
      explored.

PMID- 23156798
TI  - [A method of precise adjustment and calibration for high-resolution echelle
      spectrograph].
AB  - Echelle spectrograph is a new type of high-resolution, high-precise spectrograph,
      and its resolution can be up to tens of thousands to hundreds of thousands. In
      this case, a little error of the structure will affect the resolution and
      precision greatly, so an accurate adjustment is of importance for the echelle
      spectrograph. According to the design features, the present paper discusses the
      adjustment method for echelle spectrograph. This is an uncomplicated, quick
      method, and adapts to mini, airproof structure of echelle spectrograph. Using
      this method, the actual state is consistent with the design result. The result of
      wavelength calibration is given out, and the error is less than 0.002 nm, which
      satisfies the requirement of the system.

PMID- 23156799
TI  - [The effects of signal to noise ratio of instrument and number of wavelengths on
      the accuracy of spectral analysis].
AB  - In order to study the influence of the two factors, the signal to noise ratio
      (SNR) of instrument and number of wavelengths, on the accuracy of quantitative
      analysis in spectral modeling analysis, the influences of different SNRs, the
      number of wavelengths participating in partial least square regression, and multi
      wavelength modeling in different SNR bands were taken into account. The
      relationships between these factors and quantitative analysis accuracy were
      explored by modeling analysis experiments. The results show that the analysis
      accuracy is directly related to the SNR of instrument. And increasing
      wavelengths, especial the ones with high SNR, reflects a phenomenon that four
      times of wavelength number will bring 2 times accuracy increasing, which can
      compensate for the lack of SNR. The research provides the experimental basis and
      theoretical guidance to improve the model's quality and reduce the prediction
      error by the utilization and improvement of the instrument's SNR and the
      reasonable choice of wavelengths and bands of modeling.

PMID- 23156800
TI  - [The analysis for improving the SNR of blood components noninvasive measurement
      with DS method].
AB  - In order to increase the accuracy of blood components measurement and enhance the
      stability of prediction model, the quantitative signal-noise-ratio (SNR) analysis
      of measuring instruments based on dynamic spectrum (DS) and preprocessing method
      was conducted. The SNR of DS is increased after adding boxcar integrator,
      decreasing wavelength revolution, balancing the DS's SNR and excluding gross
      errors in preprocessing according to experiment results. Two volunteers were
      tested continuously for many times using the DS data acquiring system. The
      correlation coefficients of the each volunteer's DS data was increased from 0.934
      and 0.953 to 0.991 and 0.987, respectively. Moreover, the gap between the
      correlation coefficient of the same volunteer's DS and different volunteers' DS
      is increased too, which shows that the SNR can be improved by these methods. The
      quantitative SNR analysis can guide the way of choosing preprocessing method
      efficiently, which will create the condition for clinical application of the
      blood components noninvasive measurement.

PMID- 23156801
TI  - [Motion control of moving mirror based on fixed-mirror adjustment in FTIR
      spectrometer].
AB  - The performance of the uniform motion of the moving mirror, which is the only
      constant motion part in FTIR spectrometer, and the performance of the alignment
      of the fixed mirror play a key role in FTIR spectrometer, and affect the
      interference effect and the quality of the spectrogram and may restrict the
      precision and resolution of the instrument directly. The present article focuses
      on the research on the uniform motion of the moving mirror and the alignment of
      the fixed mirror. In order to improve the FTIR spectrometer, the maglev support
      system was designed for the moving mirror and the phase detection technology was
      adopted to adjust the tilt angle between the moving mirror and the fixed mirror.
      This paper also introduces an improved fuzzy PID control algorithm to get the
      accurate speed of the moving mirror and realize the control strategy from both
      hardware design and algorithm. The results show that the development of the
      moving mirror motion control system gets sufficient accuracy and real-time, which
      can ensure the uniform motion of the moving mirror and the alignment of the fixed
      mirror.

PMID- 23156802
TI  - [Detection of sorbic acid in food by homemade micro-spectrometer analytical
      system].
AB  - A homemade micro-spectrometer analytical system was developed for the
      quantitative determination of the sorbic acid in the food based on the
      photometric principle. And with the standard addition method it was applied to
      eliminate the interference coming from the food substrate. The detecting result
      illustrated a good relativity in the range of 0-10.0 mg x L(-1) with the linear
      correlation coefficient of 0.9989, and the sample recovery was 99.2%-99.5% with
      RSD of 0.58%. The micro-spectrometer analysis system has shown potential
      prospective application in the fields of rapid and high performance detection for
      food additives.

PMID- 23156803
TI  - [Clinical examination of olfactory and gustatory function].
AB  - OBJECTIVE: To explore changes of olfactory and gustatory functions in patients
      with olfactory dysfunction. METHOD: The 284 study subjects included 92 healthy
      volunteers, 92 with hyposmia and 100 with functional anosmia. Their olfactory and
      gustatory functions were examined using T&T olfactometer, olfactory event-related
      potentials (OERPs) and triple drop method, respectively. RESULT: The T&T results
      showed that the difference between patients with hyposmia and functional anosmia
      and healthy subjects had statistical significance. The OERPs results showed that
      patients with olfactory dysfunction had N1 and P2 waves of prolonged latency and
      reduced amplitude when compared to healthy subjects with the difference of
      statistical significance. When compared to healthy subjects, patients with
      olfactory dysfunction had clear hypogeusia and the difference had statistical
      significance. There was no significant difference between female and male groups.
      CONCLUSION: It is suggested that the apparently concomitant hypogeusia is in
      patients with olfactory dysfunction. Decreased of olfactory and gustatory
      function exhibited little or no relationship with gender. Combined examinations
      of OERPs, T&T and triple drop method, could make it possible to reflect the
      overall chemical sensory functions in subjects systematically and provide
      scientific evidence for clinical diagnosis and treatment early.

PMID- 23156804
TI  - [Expression of fascin and correlation with MVD in sinonasal inverted papilloma].
AB  - OBJECTIVE: To investigate the expression of Fascin in sinonasal inverted
      papilloma (SNIP) and the relationship between Fascin expression and microvessel
      density (MVD). METHOD: The expression of Fascin and CD34 were determined by
      immunohistochemistry in 30 cases of SNIP, 12 cases of nasal squamous cell
      carcinoma (NSCC) and 10 cases of normal inferior turbinate (IT) tissues.
      Meanwhile, CD34, measure of MVD, was counted at the same time. RESULT: Fascin was
      expressed in 17 of 30 (56.6%) cases of SNIP, 10 of 12 (83.3%) cases of NSCC and 2
      of 10 (20.0%) cases of normal IT tissues. Expression of Fascin was significantly
      increased in SNIP and NSCC compared to normal tissues (P < 0.01). MVD counts was
      23.64 +/- 2.74, 45.10 +/- 5.45, 74.76 +/- 7.32, respectively (P < 0.01). There
      was a positive correlation between the expression of Fascin and MVD counts.
      CONCLUSION: The high expression of Fascin and angiogenesis are significantly
      associated with biological behaviour of SNIP. Fascin may play an important role
      in the pathogenesis of SNIP and NSCC and synergic role with angiogenesis in
      progression of SNIP.

PMID- 23156805
TI  - [The expression and significance of smac, XIAP, caspase-3 in nonnasal inverted
      papilloma].
AB  - OBJECTIVE: To explore the expression and significance of second mitochondria
      derived activator of caspase (Smac), X-linked inhibitor of apoptosis protein
      (XIAP)and cysteine containing aspartate specific protease 3 (caspase-3) in the
      growth, development and carcinogenesis of the nonnasal inverted papilloma (NIP).
      METHOD: Immunohistochemical method was used to detect the expression of Smac,
      XIAP, caspase-3 in 10 cases of nasal cavity mucosae (NM) and 45 cases of NIP, the
      group of NIP 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,
      Caspase-3 in NIP were lower than NM, the intensity of the positive expression
      decreased with the decreasing degree of histological differentiation. There was a
      significant difference between NIP without dysplasia and SCC. It was presented
      with a progressive tendency for the expression of XIAP in the group of NM and
      NIP. The lower degree of histological differentiation, the higher intensity of
      the positive expression. The expression between NIP without dysplasia and SCC had
      a significant difference. Smac negatively correlated with XIAP (r(s) = -0.323, P
      < 0.05), XIAP negatively correlated with caspase-3 (r(s) = -0.408, P < 0.01),
      Smac positively correlated with caspase 3 (r(s) = 0.424, P < 0.01). CONCLUSION:
      Smac, XIAP, caspase 3 might be associated with the growth and carcinogenesis of
      NIP.

PMID- 23156806
TI  - [The anatomy research of expanding vision of endoscopic maxillary sinus
      operation].
AB  - OBJECTIVE: To get the anatomical method of expanding vision of endoscopic
      maxillary sinus operation to providing guidance for the satisfactory surgical
      vision by measurement of nasal cavity and maxillary sinus relative structure.
      METHOD: By anatomical measurement from 30 human cranium preparations (21 male, 9
      female), which were marinated by 10% formaldehyde solution, we tried to find out
      anatomical factors that influence expanding vision of endoscopic maxillary sinus
      operation. RESULT: Measurement of cranium preparations: respective distance
      between bone nasolacrimal canal anterior wall superior extremity, central
      extremity, bottom extremity and borderline of maxillary sinus anterior wall and
      medial wall were 0 mm, (1.90 +/- l.03) mm, (3.29 +/- 1.04) mm. Distance between
      anterior inferior part of bone nasolacrimal canal and anterior edge of inferior
      concha was (5.13 +/- 0.62) mm, and vertical distance between anterior inferior
      part of bone nasolacrimal canal and nasal bottom was (16.89 +/- 0.97) mm. The
      difference between right and left side had no significant statistic sense (P >
      0.05). Removal of the bone area: the upper and lower diameter of part of the
      inferior turbinate attachment was (9.43 +/- 1.72) mm, anteroposterior diameter
      from top to bottom was (9.76 +/- 0.83) mm, (11.39 +/- 0.50) mm, (12.85 +/- 0.66)
      mm, the upper and lower diameter of the following part of the inferior turbinate
      attachment was (13.52 +/- 0.83) mm, anteroposterior diameter from top to bottom
      was (19.89 +/- 1.37) mm, (16.59 +/- 0.77) mm, (12.48 +/- 0.91) mm. CONCLUSION:
      Dissection from inferior turbinate anterior part approach to maxillary sinus
      could expand the endoscopic operation vision.

PMID- 23156807
TI  - [The effect of biyuanshu oral liquid on the formation of Pseudomonas aeruginosa
      biofilms in vitro].
AB  - OBJECTIVE: To observe the effect of biyuanshu oral liquid on the formation of
      pseudomonas aeruginosa biofilms in vitro. METHOD: Pseudomonas aeruginosa biofilm
      was established by plate culture and detected by Scanning electron microscopy and
      AgNO3 staining. After treated with different dosages of biyuanshu oral liquid and
      erythromycin, the pseudomonas aeruginosa biofilms were observed by AgNO3 staining
      and the number of viable bacteria were measured by serial dilution. RESULT: The
      pseudomonas aeruginosa biofilms could be detected by SEM at the seventh culture
      day and it was consistent with the detection of AgNO3 staining. The biyuanshu
      oral liquid and erythromycin have the effect on inhibiting the formation of
      pseudomonas aeruginosa biofilms. But with the already formed pseudomonas
      aeruginosa biofilms the inhibition was not significant. The serial dilution
      method showed that the viable counts of bacteria of biyuanshu oral liquid and
      erythromycin treated groups were significantly lower than those untreated groups
      (P < 0.05). CONCLUSION: The biyuanshu oral liquid and erythromycin can inhibit
      the formation of pseudomonas aeruginosa biofilms in vitro.

PMID- 23156808
TI  - [Endoscopic endonasal surgery for cranial base tumor].
AB  - OBJECTIVE: To explore the application of endoscopic endonasal approach in surgery
      for skull base tumor. METHOD: From August 2000 to February 2009, retrospective
      analyses were performed on clinical data of 21 patients with skull base lesions
      treated by endoscopic endonasal surgery. There were 3 chordoma, 6 olfactory
      neuroblastoma, 4 squamous cancer, 5 malignant melanoma, 1 mucoepidermoid
      carcinoma, 2 sphenoidal malignant adenoma. RESULT: Total tumor removal was
      obtained in 21 cases,subtotal removal in 2 cases. With follow up of 24 to 108
      months, 4 cases were recurred, 5 cases were dead. The complications included
      cerebrospinal fluid (CSF) leak in 2 patients, intracranial infection after the
      endoscopic surgery in 1 patient. In the two patients with CSF leak, one case
      cured by internal medicine and another cured by endoscopic surgery. CONCLUSION:
      The endoscopic endonasal surgery could provide sufficient treatment for skull
      base tumor, and is a safe, minimally invasive and efficient procedure, but
      indication should be exactitude selected.

PMID- 23156809
TI  - [The study of risk factors of nasal septal perforation in rats].
AB  - OBJECTIVE: To study the risk factors and interaction of nasal septal perforation
      (NSP) in rats. METHOD: Animals (n=120) that underwent unilateral nasal
      obstruction using Merocel nasal packing or gelfoam with/without standard
      staphylococcus aureus inoculation were observed for the formation of NSP at 2, 3,
      5, and 7 days after operation by endoscope system. Following sacrifice at 7 days,
      the obtained nasal secretions were prepared for bacterial culture. Experimental
      interventions were compared with normal controls (n=10). RESULT: Perforation of
      nasal septum was observed in 80% of the animals accepted nasal obstruction using
      Merocel nasal packing with standard staphylococcus aureus inoculation in 3 days
      (P < 0.01), while in 70% of those using abacterial Merocel nasal packing in 5
      days (P < 0.05) and no significant difference than that of before (P > 0.05).
      There was a weak region in anteroinferior nasal septum in rats, which the almost
      NSPs located in. The position of NSP does not overlap Merocel. CONCLUSION: The
      interaction of risk factors contributes to NSP. The occurrence of NSP mainly
      depends on the construction of nasal septum, while dysaemia is also necessary.
      Obstruction of nasal drainage and infection promote the development of NSP.

PMID- 23156810
TI  - [A longitudinal study of balance in migraineurs].

PMID- 23156811
TI  - [A meta-analysis compare rapid rhino with merocel for nasal packing].
AB  - OBJECTIVE: To assess the efficacy and adverse reaction of nasal packing materials
      Rapid Rhino and Merocel. METHOD: We searched the database PubMed, EMBASE,
      Cochrane Library, CBM, CNKI, VIP and WANFANG database on line by computer, and
      traced the related references. Randomized controlled trials(RCTs) of rapid rhino
      and merocel as nasal packing materials were included. The quality of the included
      documents was evaluated by the criterion of Cochrane handbook 5.1. The cochrane
      collaboration's Revman 5.1 software was used for data analysis. RESULT: Four RCTs
      involving 115 patients were identified. Meta-analyses showed that Rapid Rhino
      produced significantly lower pain and discomfort during insert of pack [MD =
      1.37, 95% CI (0.13, 2.60), P < 0.05], whereas less pain and discomfort during
      removal of pack [MD = 2.88, 95% CI (2.34, 3.41), P < 0.01]. Rapid Rhino
      associated with a significantly slighter degree of fullness raised after
      insertion [MD = 1.15, 95% CI (0.75, 1.55), P < 0.01, and the same situation
      happened after 6 hours [MD = 1.15, 95% CI (0.75, 1.55), P < 0.01]. Rapid rhino
      caused to less reactionary bleeding when pack removal [MD = 0.26, 95% CI (0.12,
      0.39), P < 0.01], rapid rhino was easier for the healthcare worker during insert
      and removal. There was no significant difference between two packs on the
      efficiency of hemostatic [OR = 1.00, 95% CI (0.38, 2.61), P > 0.05]. CONCLUSION:
      The application of Rapid Rhino caused less pain and fullness, leaded to slighter
      bleed than Merocel when insertion and removal. There was no significant
      difference between two packs on the efficiency of hemostatic when used for
      epistaxis or after routine nasal surgery.

PMID- 23156812
TI  - [Comparison the therapeutic effects of the comprehensive treatment of surgery
      combined with radiotherapy and radiotherapy treatment only in laryngopharyngeal
      carcinoma cases].
AB  - OBJECTIVE: Comparing the difference between the effect of comprehensive treatment
      and that of radiotherapy only in laryngopharyngeal carcinoma cases. METHOD:
      Analyzing clinical data of 68 cases of laryngopharyngeal carcinoma treated in our
      department from June 2003 to December 2009. Among them, 40 cases were treated by
      comprehensive treatment of surgery combined with radiotherapy (group A), 28 cases
      by radiotherapy only (group B). RESULT: The three-year survival rate of group A
      and B were 75.6% (31/41) and 26.7% (4/15), respectively, and the five-year
      survival rate of the two groups were 56.1% (23/41) and 13.3% (2/15),
      respectively. CONCLUSION: For laryngopharyngeal carcinoma cases, the therapeutic
      effect of comprehensive treatment was much better than that of the radiotherapy
      only, not only could improve the survival rate, but also could make the life
      quality after treatment better.

PMID- 23156813
TI  - [Clinical investigation of 26 cases of fungal rhinosinusitis endoscopic surgery].

PMID- 23156814
TI  - [Fifty two patients with chronic dacryocystitis treated by dacryocystorhinostomy
      under endoscope and T drainage tube inserting].

PMID- 23156815
TI  - [A report of the solitary fibrous tumor in nasal cavity].
AB  - A 56-year-old woman, with a 1-day history of bilateral nose haemorrhagia,
      predominantly on the right side, sometimes manifested rhinocnesmus, sneeze and
      water rhinorrhea, no nose obstruction, and no fever. Endoscopy revealed a smooth
      and pinkish mass that completely obstructed the right nasal cavity and extended
      to the base of nose. Computed tomography showed a large mass that occupied the
      entire right nasal cavity and part of the right maxillary sinus, ethmoidal sinus
      and frontal sinusitis.

PMID- 23156816
TI  - [Delayed abscess of nasal septum caused by bipolar coagulation treatment for
      nosebleed: a case report].
AB  - Clinical manifestation bipolar coagulation treatment for nosebleed. The patient
      was affected by nasal obstruction, fever and headache three weeks after
      operation. Clinical and laboratory examination nasal septum's bilateralism
      knuckle, soft quality, puncture with purulent secretion. Diagnose: abscess of
      nasal septum.

PMID- 23156817
TI  - [Delayed abscess of nasal septum caused by bipolar coagulation treatment for
      nosebleed: a case report].
AB  - Clinical manifestation bipolar coagulation treatment for nosebleed. The patient
      suffered from obstruction,fever and headache three weeks after operation.
      Clinical and laboratory examination nasal septum bilateralism knuckle, soft
      quality, puncture with purulent secretion. Diagnose: abscess of nasal septum.

PMID- 23156818
TI  - [The research of intensity focused ultrasound on the treatment of allergic
      rhinitis].
AB  - Allergic rhinitis is a common disease in otorhinolaryngology, there are lots of
      physiotherapies now, the overview of the research of intensity focused ultrasound
      on the treatment of allergic rhinitis was mainly reviewed.

PMID- 23156819
TI  - Doctors of interest. Recipients of suspect drug-company payments academic medical
      centers, have drawing attention of federal fraud enforcers.
AB  - As the federal government begins to focus more on wasteful healthcare spending,
      doctors' relationships with drug companies are coming under scrutiny. Many times,
      those relationships are legitimate, says Mary Riordan, left, a senior counsel to
      HHS' inspector general's office. "There are other situations where the
      relationship between the doctor and the manufacturer is suspect".

PMID- 23156820
TI  - Ryan: plan is bipartisan. The 'time has come' for premium support, he says.

PMID- 23156821
TI  - Bare necessities. Little state progress on defining coverage requirements.

PMID- 23156822
TI  - Challenging the alternative. Rule targets advantage of some transplant systems.

PMID- 23156823
TI  - Ups and downs. Investment portfolios see no returns in 2011.

PMID- 23156824
TI  - Medicare, front and center. Ryan re-energized the debate; now it's time for
      everyone to show their plans.

PMID- 23156825
TI  - Reducing readmissions. Data system helps address complex questions, improve
      medicine.

PMID- 23156826
TI  - Supply-side economics. Purchasing practices at hospitals and health systems
      continue to evolve, with the supply chain continuing to be a target for large non
      labor cost savings.

PMID- 23156828
TI  - Electronic medical records professional.

PMID- 23156827
TI  - Evolving accreditation. Rise of ACOs prompts group to expand services beyond
      ambulatory care.

PMID- 23156829
TI  - Foreword: celebrating the first ten years of research excellence from the Jackson
      Heart Study.

PMID- 23156830
TI  - Foreword: applauding research efforts addressing disparities in cardiovascular
      disease.

PMID- 23156831
TI  - Foreword: a tribute to the work of JHS investigators, the Jackson community and
      NIH scientists.

PMID- 23156832
TI  - Introduction: Jackson Heart Study--building a 21st century platform for
      discovery, service and training to address an American health priority.

PMID- 23156833
TI  - Cardiovascular disease outcomes: priorities today, priorities tomorrow for
      research and community health.
AB  - The disparities and differences in heart disease and stroke among Black, White
      and Hispanic populations tell a compelling and continuing story that should drive
      research agendas to improve health outcomes. With Black men and women having the
      highest prevalence of hypertension, Black females having higher rates of coronary
      heart disease, stroke and breast cancer than White females, and Blacks, at all
      ages, having a greater risk for stroke mortality than Whites, researchers and
      health care providers must understand the clinical appropriateness of treatment
      for different states of disease among distinct populations. Further, to eliminate
      health disparities, the health care systems and legal regulatory climate must
      facilitate access to care while biases, prejudices and stereotyping by health
      care providers and all those in the health care system must be eliminated.
      Importantly, research continues to illustrate that many are dying prematurely or
      have advanced stages of disease because of disparate care. This article explores
      four strategies to address inequitable care and to work toward eliminating poorer
      health outcomes among minorities. First, those who deliver health care must adopt
      a quality-focused approach that improves the care of all patients while
      facilitating the reduction and elimination of health disparities. Second,
      cultural awareness and cultural competency must be improved. Third, we must
      remove barriers to access and promote public policies that lead to greater health
      awareness and healthier environments. Lastly, but most importantly, we need a
      prevention focus as the reduction in the onset of disease is the first step
      towards improving health outcomes.

PMID- 23156834
TI  - The social context of cardiovascular disease: challenges and opportunities for
      the Jackson Heart Study.
AB  - African Americans have higher rates of cardiovascular disease (CVD) than Whites
      and the racial gap in heart disease is widening over time. There are especially
      striking patterns of the earlier onset of disease, greater severity of illness
      and large racial differences in CVD even when Blacks and Whites are compared at
      the same level of economic status. This paper outlines critical research
      opportunities for the Jackson Heart Study to advance the science base for
      understanding and effectively addressing racial disparities in CVD. These
      include: 1) the study of CVD by using a life course perspective; 2)
      comprehensively characterizing social stressors; 3) expanding our analysis of how
      racism affects health; 4) explicating variation in the levels and impact of risk
      factors; 5) advancing our understanding of the contribution of genetics to CVD;
      6) understanding resilience and its effects on CVD; and 7) identifying how
      economic crises can shape CVD risk.

PMID- 23156835
TI  - The revolution in risk assessment and disease detection made possible with non
      invasive imaging: implications for population science.
AB  - The ability to quantify subclinical disease to assess cardiovascular disease is
      greatly enhanced by modern medical imaging techniques that incorporate concepts
      from biomedical engineering and computer science. These techniques' numerical
      results, known as quantitative phenotypes, can be used to help us better
      understand both health and disease states. In this report, we describe our
      efforts in using the latest imaging technologies to assess cardiovascular disease
      risk by quantifying subclinical disease of participants in the Jackson Heart
      Study. The CT and MRI exams of the Jackson Heart Study have collected detailed
      information from approximately 3,000 participants. Analyses of the images from
      these exams provide information on several measures including the amount of
      plaque in the coronary arteries and the ability of the heart to pump blood. These
      measures can then be added to the wealth of information on JHS participants to
      understand how these conditions, as well as how clinical events, such as heart
      attacks and heart failure, occur in African Americans.

PMID- 23156836
TI  - The impact of traditional risk factor development on the life course of
      cardiovascular diseases.
AB  - This report discusses the profound impact of established risk factors for
      coronary heart disease (CHD) and cardiovascular disease (CVD), from the
      perspective of both shortterm and lifetime risks. Emerging data have confirmed
      the major importance of aggregate risk factor burden in middle and older age on
      remaining lifetime risks for CVD. The relatively new concept of the ideal
      cardiovascular health factor profile will play a central role in plans to improve
      the longevity, healthy longevity, and quality of life and health care costs of
      all Americans. In this context, the agenda of the Jackson Heart Study should
      promote understanding of and identify means for enhancing the roles of CVD
      prevention and health promotion among African Americans.

PMID- 23156837
TI  - CVD health factors and CVD risk factors: state of the science, emerging
      priorities part 2: obesity prevention.
AB  - This report outlines a course of action to prevent obesity and stall the obesity
      epidemic now underway in the United States and other parts of the world. While
      African Americans and Hispanics are most vulnerable to obesity, the etiology of
      obesity shows that both genetic and environmental factors are responsible for
      overweight and obesity. Although obesity is familial, genes may not be the main
      culprit; and, in fact, explain < 20% of the obesity prevalence. Clearly,
      environmental factors (specifically those related to energy intake [diet] and
      energy output [physical activity]) are more often associated with obesity.
      Patients with multiple risk factors, including obesity, for cardiovascular
      disease need to be treated aggressively with lifestyle modifications and
      medications, when necessary, to affect positive cardiovascular health outcomes.
      However, a wiser, healthier approach to obesity is to prevent it from occurring
      in the first place.

PMID- 23156838
TI  - Genes and environments: moving toward personalized medicine in the context of
      health disparities.
AB  - Understanding gene-environment interactions that may influence disease is the
      cornerstone of a personalized medicine approach built on diagnostics, risk
      assessment/risk modification, pharmacogenetics and biology. Although genetic and
      personalized medicine can influence clinical decision making, currently most
      genetic information is based on populations of European ancestry. Additional
      human genome research must include diverse populations in order to assess the
      impact DNA sequence variation and environmental influences have on human disease
      risk. Within this article, we present a brief overview of human genome variation
      and discuss how epigenomics may influence gene expression. Examples of gene
      environment interactions are explored and linked to several health disparities
      and health outcomes among communities of color. With the Jackson Heart Study
      poised to take the next steps in examining genes and the environment in ways that
      other cohorts cannot, we will be closer to a more inclusive personalized medicine
      goal that transforms medicine from curative to preemptive for all.

PMID- 23156839
TI  - The Jackson Heart Study of the future.

PMID- 23156840
TI  - Part 1. Biologic responses in rats and mice to subchronic inhalation of diesel
      exhaust from U.S. 2007-compliant engines: report on 1-, 3-, and 12-month
      exposures in the ACES bioassay.
AB  - The Health Effects Institute and its partners conceived and funded a program to
      characterize the emissions from heavy-duty diesel engines compliant with the 2007
      and 2010 on-road emissions standards in the United States and to evaluate
      indicators of lung toxicity in rats and mice exposed repeatedly to diesel exhaust
      (DE*) from 2007-compliant engines. The preliminary hypothesis of this Advanced
      Collaborative Emissions Study (ACES) was that 2007-compliant on-road diesel
      emissions ". . . will not cause an increase in tumor formation or substantial
      toxic effects in rats and mice at the highest concentration of exhaust that can
      be used . . . although some biological effects may occur." This hypothesis is
      being tested at the Lovelace Respiratory Research Institute (LRRI) by exposing
      rats by chronic inhalation as a carcinogenicity bioassay, measuring indicators of
      pulmonary toxicity in rats after 1, 3, 12, and 24-30 months of exposure (final
      time point depends on the survival of animals), and measuring similar indicators
      of pulmonary toxicity in mice after 1 and 3 months of exposure. This report
      provides results of exposures through 3 months in rats and mice. Emissions from a
      2007-compliant, 500-horsepower-class engine and aftertreatment system operated on
      a variable-duty cycle were used to generate the animal inhalation test
      atmospheres. Four treatment groups were exposed to one of three concentrations
      (dilutions) of exhaust combined with crankcase emissions, or to clean air as a
      negative control. Dilutions of exhaust were set to yield average integrated
      concentrations of 4.2, 0.8, and 0.1 ppm nitrogen dioxide (NO2). Exposure
      atmospheres were analyzed by daily measurements of key components and periodic
      detailed physical-chemical characterizations. Exposures were conducted 16 hr/dy
      (overnight), 5 dy/wk. Rats were evaluated for hematology, serum chemistry,
      bronchoalveolar lavage (BAL), lung cell proliferation, and histopathology after 1
      month of exposure, and the same indicators plus pulmonary function after 3
      months. Mice were evaluated for BAL, lung cell proliferation, and respiratory
      tract histopathology after 1 month of exposure, and the same indicators plus
      hematology and serum chemistry after 3 months. Samples from both species were
      collected for ancillary studies performed by investigators who were not at LRRI
      and were funded separately. Exposures were accomplished as planned, with average
      integrated exposure concentrations within 20% of the target dilutions. The major
      components were the gaseous inorganic compounds, nitrogen monoxide (NO), NO2, and
      carbon monoxide (CO). Minor components included low concentrations of diesel
      particulate matter (DPM) and volatile and semivolatile organic compounds (VOCs
      and SVOCs). There were no exposure-related differences in mortality or clinically
      evident morbidity. Among the more than 100 biologic response variables evaluated,
      the majority showed no significant difference from control as a result of
      exposure to DE. There was evidence of early lung changes in the rats, accompanied
      by a number of statistically significant increases in inflammatory and oxidative
      stress indicators, and some evidence of subtle changes in pulmonary function. In
      general, statistically significant effects were observed only at the highest
      exposure level. The mice did not have the same responses as the rats, but did
      have small but statistically significant increases in lavage neutrophils and the
      cytokine IL-6 at 1 month (but not at 3 months). These findings suggest that the
      rats were more sensitive than mice to the subchronic exposures.

PMID- 23156841
TI  - Part 2. Assessment of genotoxicity after exposure to diesel exhaust from U.S.
      2007-compliant diesel engines: report on 1- and 3-month exposures in the ACES
      bioassay.
AB  - Micronucleus (MN*) formation is a well-established endpoint in genetic
      toxicology; studies designed to examine MN formation in vivo have been conducted
      for decades. Conditions that cause double-strand breaks or disrupt the proper
      segregation of chromosomes during division result in an increase in MN frequency.
      Thus this endpoint is commonly employed in preclinical studies designed to assess
      the potential risks of human exposure to a myriad of chemical and physical
      agents, including inhaled diesel exhaust (DE). As part of the Advanced
      Collaborative Emissions Study (ACES) this investigation examined the potential of
      inhaled DE to induce chromosome damage in chronically exposed rodents. The ACES
      design included exposure of both rats and mice to DE derived from 2007-compliant
      heavy-duty engines. The exposure conditions consisted of air control and
      dilutions of DE resulting in three levels of exposure. At specified times, blood
      samples were collected, fixed, and shipped by the bioassay staff to Litron
      Laboratories for further processing and analysis. Significant improvements have
      been made to MN scoring by using objective, automated methods such as flow
      cytometry, which allows for the detection of micronucleated reticulocytes (MN
      RET), micronucleated normochromatic erythrocytes (MN-NCE), and reticulocytes
      (RETs) in peripheral blood samples from mice and rats. By using a simple staining
      procedure coupled with rapid and efficient analysis, many more cells were
      examined in less time than was possible in traditional, microscopy-based MN
      assays. Thus, for each sample, 20,000 RETs were scored for the presence of MN. In
      the chronic-exposure bioassay, blood samples were obtained from independent
      groups of exposed animals at specific time points throughout the course of the
      entire study. This automated method is supported by numerous regulatory
      guidelines and meets the requirements for an Organization of Economic Cooperation
      and Development (OECD)-compliant assay for genotoxicity. Statistical approaches
      employed analysis of variance (ANOVA) to compare effects of sex, exposure
      condition, and duration, as well as their interactions. This initial assessment
      of MN was performed on both mouse and rat blood samples from the 1-month and 3
      month exposures. The data from mice demonstrate the well established, sex-based
      difference in MN-RET and MN-NCE frequencies regularly observed in this species,
      with females exhibiting slightly lower frequencies. There were no sex-based
      differences observed in rats. An examination of the mean frequencies across the
      exposure groups and durations of exposure did not show an appreciable induction
      of MN at the 1- or 3-month exposures in either species. Further statistical
      analyses did not reveal any significant exposure-related effects. An examination
      of the potential genotoxic effects of DE is clearly valuable as part of a large
      scale chronic-exposure bioassay. The data and observations from the 1-and 3-month
      exposure studies will eventually be combined with the results from the 1- and 2
      year exposure studies to provide a comprehensive examination of chronic exposure
      to DE in a rodent model. This examination of chromosome damage serves an
      important role in the context of the entire ACES bioassay, which was designed to
      assess the safety of diesel combustion engines.

PMID- 23156842
TI  - Part 3. Assessment of genotoxicity and oxidative stress after exposure to diesel
      exhaust from U.S. 2007-compliant diesel engines: report on 1- and 3-month
      exposures in the ACES bioassay.
AB  - Human health hazards due to diesel exhaust (DE*) exposure have been associated
      with both solvent and combustion components. In the past, diesel engine exhaust
      components have been linked to increased mutagenicity in cultures of Salmonella
      typhimurium and mammalian cells (Tokiwa and Ohnishi 1986). In addition, DE has
      been shown to increase both the incidence of tumors and the induction of 8
      hydroxy-deoxyguanosine adducts (8-OHdG) in ICR mice (Ichinose et al. 1997).
      Furthermore, DE is composed of a complex mixture of polycyclic aromatic
      hydrocarbons (PAHs) and particulates. One such PAH, 3-nitrobenzanthrone (3-NBA),
      has been identified in DE and found in urban air. 3-NBA has been observed to
      induce micronucleus formation in DNA of human hepatoma cells (Lamy et al. 2004).
      The purpose of the current research, which is part of the Advanced Collaborative
      Emissions Study (ACES), a multidisciplinary program being carried out by the
      Health Effects Institute and the Coordinating Research Council, is to determine
      whether improvements in the engineering of heavy-duty diesel engines reduce the
      oxidative stress and genotoxic risk associated with exposure to DE components. To
      this end, the genotoxicity and oxidative stress of DE from an improved diesel
      engine was evaluated in bioassays of tissues from Wistar Han rats and C57BL/6
      mice exposed to DE. Genotoxicity was measured as strand breaks using an alkaline
      modified comet assay. To correlate possible DNA damage found by the comet assay,
      measurement of DNA-adduct formation was evaluated by a competitive enzyme-linked
      immunosorbent assay (ELISA) to determine the levels of free 8-OHdG found in the
      serum of the animals exposed to DE. 8-OHdG is a specific modified base indicating
      an oxidative type of DNA damage to DNA nucleotides. In addition, a thiobarbituric
      acid reactive substances (TBARS) assay was used to assess oxidative stress and
      damage in the form of lipid peroxidation in the hippocampus region of the brains
      of DE-exposed animals. Results from the comet assay showed no significant
      differences in rats between the control and exposed groups (P = 0.53, low
      exposure; P = 0.92, medium exposure; P = 0.77, high exposure) after 1 month of DE
      exposure. There were no differences between sexes in the responses of rats to
      these exposures. Likewise, there were no significant differences found after 3
      months of exposure. Similarly, no significant differences were found between the
      mice exposed for 1 and 3 months to DE, nor were any differences found between
      sexes. Measurements of 8-OHdG in both mice and rats showed no significant
      difference among DE exposure groups (P = 0.46, mice; P = 0.86, rats). In mice,
      measured 8-OHdG was lower in the 3-month group than the 1-month group. In rats,
      the inverse was true. In mice, no significant differences in the levels of lipid
      peroxidation, as measured by TBARS, were found between the controls and DE
      exposure groups (P = 0.92), nor were there any differences between sexes. In
      rats, comparisons between the control and low-exposure groups approached
      significance, but no significant differences were found between the other DE
      exposure groups. Additionally, in rats, there were no significant differences
      between the 1- and 3-month DE exposure groups.

PMID- 23156843
TI  - Part 4. Effects of subchronic diesel engine emissions exposure on plasma markers
      in rodents: report on 1- and 3-month exposures in the ACES bioassay.
AB  - Although epidemiologic and experimental studies suggest that exposure to diesel
      exhaust (DE*) emissions causes adverse cardiovascular effects, neither the
      specific components of DE nor the mechanisms by which DE exposure could induce
      cardiovascular dysfunction and exacerbate cardiovascular disease (CVD) are known.
      Moreover, because the advance of new technologies has resulted in cleaner fuels
      and decreased engine emissions, there is even more uncertainty about the
      relationship between DE exposure and cardiovascular health effects. To address
      this ever-changing baseline of engine emissions, we tested for exposure-, sex-
      and duration-dependent alterations in plasma markers following subchronic
      exposure of mice and rats to DE emissions from a 2007-compliant diesel engine.
      Many plasma markers--several recognized as known human CVD risk factors--were
      measured in the plasma of rodents exposed to 1 or 3 months of air (the control)
      or DE emissions. Few changes in plasma markers resulted from exposure to DE,
      although significant exposure-level-dependent increases in total cholesterol and
      high-density lipoprotein (HDL) cholesterol were observed in male rats after 1
      month of DE exposure, an effect that was neither sustained nor observed in any
      other group. These data indicate that DE emissions from a 2007-compliant diesel
      engine as tested in this study had little adverse effect on CVD markers in
      rodents.

PMID- 23156844
TI  - Immune system is an important system of the body for maintenance of health.

PMID- 23156845
TI  - Staphylococcus aureus superantigens and their role in eosinophilic nasal polyp
      disease.
AB  - Nasal polyposis is a chronic disease of the upper airways which adversely affects
      the quality of life of patients. Its pathophysiology is still unclear. Recently,
      several studies have shown different inflammatory pathways which relate to both
      innate and adaptive immune responses. Moreover, different phenotypes may exist in
      different ethnic groups of patients. This article will review recent data
      regarding the type of inflammation, cytokine profiles, involvement of macrophages
      and dendritic cells, and the impact of various organisms (especially
      Staphylococcus aureus and its superantigens) and their association with lower
      airway disease (especially asthma).

PMID- 23156846
TI  - A double-masked comparison of 0.1% tacrolimus ointment and 2% cyclosporine eye
      drops in the treatment of vernal keratoconjunctivitis in children.
AB  - OBJECTIVE: To compare the efficacy of 0.1% tacrolimus (FK-506) ophthalmic
      ointment with 2% cyclosporine eye drops in the treatment of vernal
      keratoconjunctivitis (VKC). DESIGN: Prospective double-masked randomized
      comparative trial. PARTICIPANTS: Twenty-four VKC patients were enrolled into the
      study. Their mean age was 9.61 +/- 2.55 years. Twelve patients were allocated
      into the FK-506 group and the other twelve into the cyclosporine group. Their
      baseline characteristics were similar between groups. METHODS: After a 2 week run
      in period, patients were randomized into 2 groups in a double-masked, parallel
      fashion. Group A received 0.1% FK-506 eye ointment twice daily with placebo eye
      drops four times daily for 8 weeks. Group B received 2% cyclosporine eye drops
      with placebo ointment for the same duration. All patients received an open
      treatment with 0.1% FK-506 eye ointment for another 4 weeks. Subjective ocular
      symptoms and side effects were recorded by patients once daily, during the entire
      period. Objective ocular signs were evaluated and scored at each follow up visit.
      MAIN OUTCOME MEASURE: Improvement of total subjective symptom scores per day
      (TSSS) within group and between groups at various time points. RESULTS: For
      within group comparison, there was a significant decrease in TSSS, compared to
      their baselines, at weeks 4 and 8, in both treatment groups. However, no
      statistical difference in TSSS was noted between groups at any time point. Total
      ocular sign scores (TOSS) in the FK-506 group decreased significantly at weeks 4
      and 8 compared to baseline. Although there was a decrease of TOSS in the
      cyclosporine group, the difference did not reach statistical significance. Side
      effect scores reduced significantly in both groups at week 4 compared to their
      respective baselines (p = 0.034 in the FK506 group and p = 0.003 in the
      cyclosporine group). There was no significant difference in the comparison
      between groups on TOSS and side effect scores at any time point of the study.
      During the open FK-506 period, patients in cyclosporine group showed further
      reduction of both TSSS and TOSS. However, these changes were not statistically
      significant (p > 0.05). CONCLUSION: 0.1% FK-506 eye ointment and 2% cyclosporine
      were both effective in treatment of VKC. 0.1% FK-506 could become another viable
      therapeutic option for VKC.

PMID- 23156847
TI  - The effect of acute exhaustive and moderate intensity exercises on nasal cytokine
      secretion and clinical symptoms in allergic rhinitis patients.
AB  - BACKGROUND: Allergic rhinitis is an inflammation of the nasal mucosa in response
      to allergens. There is evidence that exercise can significantly improve personal
      health and has positive effects on immune function. However, the effects of acute
      exercise on the inflammatory response and clinical symptoms in patients with
      allergic rhinitis are still unclear. PURPOSE: The aim of the present study was to
      determine the effects of acute exhaustive and moderate exercises on cytokine
      levels and clinical symptoms in patients with allergic rhinitis. METHODS:
      Thirteen allergic rhinitis patients (AR) and 14 healthy subjects (C) were
      required to complete two running exercise protocols, which included an exhaustive
      exercise bout using the Bruce protocol performed to exhaustion and moderate
      exercise performed at 65-70% HRR for 30 minutes. Physiological characteristics,
      allergic rhinitis symptoms, and cytokine secretions and serum levels were
      comparatively analyzed before and after each type of exercise. RESULTS: The total
      immunoglobulin E levels in the AR group were significantly higher than in C group
      (p < 0.05). Rhinitis symptoms scores were significantly decreased (p < 0.05)
      after both exhaustive exercise (7.69 to 1.23 points) and moderate exercise (6.46
      to 0.53 points) in the AR group. The ratio of interleukin-2 and interleukin-4 (IL
      2/IL-4) in nasal secretions after moderate exercise was significantly higher than
      those after exhaustive exercise in both the C and AR groups (p < 0.05).
      CONCLUSIONS: The data demonstrate that both exhaustive and moderate-intensity
      exercise resulted in a significant improvement in the symptoms of allergic
      rhinitis. However, a significantly enhanced IL-2/IL-4 ratio was found following
      acute moderate exercise intensity. We propose that moderate-intensity exercise is
      more effective than exhaustive exercise in enhancing immune function for allergic
      rhinitis patients.

PMID- 23156848
TI  - Inpatient asthma mortality in a tertiary referral hospital from 2000 to 2010.
AB  - OBJECTIVE: Asthma is a common respiratory disease, the prevalence of which varies
      according to multiple demographic and economic factors. The availability of
      therapy and implimentation of treatment guidelines has made the asthma mortality
      rate stable or gradually in decline. This study was conducted to evaluate the
      mortality trend of asthmatic patients who died during hospitalization in a
      tertiary care center. METHODS: A retrospective study of hospitalized asthmatic
      patients was conducted by reviewing medical records selected on the basis of
      primary or secondary diagnosis of asthma, between January 2000 and December 2010.
      The record review focused on the patients admitted to the institution who died
      with the principal diagnosis of asthma or having asthma as a co-morbidity.
      RESULTS: Between January 2000 and December 2010, a total of 540,365 patients were
      hospitalized. Of these, 553 patients were admitted with their primary or the co
      principal diagnosis of asthma. In the asthma group that were admitted, 3 male and
      9 female patients died during this period, or 2.17% of asthma admissions. Eight
      patients died in the first five years of the study, compared to 4 in the second
      half. CONCLUSION: The mortality rate of asthma in hospitalized patients has been
      declining in the last ten years. This finding has shown the importance of long
      term medication used to provide good disease control and the use of asthma
      treatment guidelines which may lead to the overall decreases in mortality rate.

PMID- 23156849
TI  - Potent inflammatory cytokine response following lung volume recruitment maneuvers
      with HFOV in pediatric acute respiratory distress syndrome.
AB  - OBJECTIVE: Lung volume recruitment maneuver (LVRM) may improve gas exchange but
      inflating the lungs to nearly vital capacity may cause further lung injuries. Our
      aim was to determine the potent inflammatory cytokine response following lung
      volume recruitment (LVRM) with high frequency oscillator ventilation (HFOV) in
      pediatric acute respiratory distress syndrome (ARDS). METHODS: We prospectively
      recruited pediatric patients (age >1 month - <15 year old) with a diagnosis of
      ARDS within 72 hrs of PICU admission. They underwent the LVRM protocol combined
      with HFOV. Any enrolled subject who had a 20% improvement in PaO2/FiO2 (PF ratio)
      1 hr after the LVRM we classified as a responder. Baseline clinical data were
      recorded. Blood was also drawn at baseline, 1 & 24 hrs after LVRM and kept for
      further sICAM-1, IL-6 & IL-8 analysis. RESULTS: Eighteen children with ARDS were
      enrolled. Their mean age was at 6.8 +/- 6.1 years (mean +/- SD). The initial
      oxygen index (iOI) was at 26.8 +/- 17.8 (11.5-84.9). There was no significant
      differences in sICAM-1, IL-6 and IL-8 levels at baseline; (34 +/- 17.5, 121.7 +/-
      115.15, 601.5 +/- 675 pg/ml); 1 hr (39.6 +/- 28.7, 99.8 +/- 75.5, 617.4 +/- 692.5
      pg/ml) and at 24 hrs (44.23 +/- 34.4, 109.4 +/- 63.9, 737.6 +/- 922.3 pg/ml)
      following LVRMs, respectively. However, there was significant difference in the
      elevation of sICAM-1 levels (%change) from baseline in responders (-1.8 +/-
      12.2%) vs. non-responders (47.65 +/- 43.5%) at 1 hr. Additionally, sICAM-1 levels
      were also significantly higher at baseline, 1 hr and 24 hrs in non-survivors as
      compared with survivors. CONCLUSION: There was no significant elevation of potent
      inflammatory cytokines that may indicate further lung injuries in the majority of
      our patients. However, there was significant elevation of sICAM-1 levels in non
      responders and in those who did not survive that may indicate more lung injuries
      in these individuals.

PMID- 23156851
TI  - The effect of desloratadine on patch test reactions in Chinese patients.
AB  - BACKGROUND: Few data on the effect of antihistamines on patch test results in
      Chinese patients are currently available. OBJECTIVES: To evaluate the effect of
      desloratadine on patch test reactions. METHODS: Patients known to have at least
      one strongly positive (+ +) test with an allergen were re-patch tested after 14
      to 70 days (average time interval 26.3 days) of administering oral desloratadine
      5 mg twice a day for 5 days before and during the test. Patch testing was
      performed with the previously recognized allergen according to the guidelines of
      the ICDRG. The -to + + + system was converted into numeric values (0, 1, 2, 3, 4)
      for statistic evaluation. RESULTS: Of the 58 chambers (47 patients), which were
      all strongly positive (+ +) during the 1st patch test, the situation was
      unchanged in 51 chambers; 4 + reactions and 2 + + + reactions were observed; and
      1 chamber was negative. There was no statistically significant difference when
      comparing the scores of the 1st assessment with those of the 2nd (p = 0.206). If
      the patch test reaction of the patient who dropped out of the trial had changed
      from strongly positive (+ +) to negative, there would still have been no
      statistically significant difference between the score of the 1st assessment with
      those of the 2nd ( p = 0.107). CONCLUSIONS: The reaction of a patch test is not
      hampered by doubling dose of desloratadine. The anti-inflammatory effects of
      desloratadine on patch test reaction may be limited.

PMID- 23156850
TI  - Caesarean section and asthma in Malaysian children: a case-control study.
AB  - BACKGROUND: Birth cohort studies in some countries have shown a link between
      caesarean section and asthma. AIM: To determine if there is an association
      between asthma and delivery via caesarean section in Malaysian children. METHOD:
      This is a case-control study involving 156 children aged 3-15 years old, in a
      tertiary hospital in Kuala Lumpur, Malaysia. Seventy-eight children with a
      confirmed diagnosis of asthma and seventy-eight age-matched controls (no history
      of asthma or wheezing) were enrolled. Demographic data including mode of delivery
      and family history of allergic disorders was obtained. Total serum immunoglobulin
      E (IgE) was measured and skin prick tests (SPT) to 6 common aeroallergens were
      performed. RESULTS: The median age of the patients was 8 years old. One hundred
      and three (66%) children were delivered via normal vaginal delivery, 8 (5.1%) via
      assisted vaginal delivery and 45 children (28.9%) via caesarean section. Delivery
      via caesarean section was not significantly associated with asthma (OR = 1.21
      [95% CI 0.60-2.41], p = 0.596). Children delivered via caesarean section did not
      have higher IgE levels nor were they more sensitized to aeroallergens. Multiple
      logistic regression showed that asthma was significantly associated with a
      positive family history of atopy (OR = 13.8 [95% CI 5.96, 32.1], p < 0.001).
      Introduction of semi-solid food after 6 months old had a protective effect
      against asthma (OR = 0.97 [95% CI 0.94, 0.99], p = 0.034). CONCLUSION: Childhood
      asthma in Malaysian children was not associated with delivery by caesarean
      section.

PMID- 23156852
TI  - A two-step non-flowcytometry-based naive B cell isolation method and its
      application in Staphylococcal enterotoxin B (SEB) presentation.
AB  - BACKGROUND: To study the role of human naive B cells in antigen presentation and
      stimulation to naive CD4+ T cell, a suitable method to reproducibly isolate
      sufficient naive B cells is required. METHODS: To improve the purity of isolated
      naive B cells obtained from a conventional one-step magnetic bead method, we
      added a rosetting step to enrich total B cell isolates from human whole blood
      samples prior to negative cell sorting by magnetic beads. The acquired naive B
      cells were analyzed for phenotypes and for their role in Staphylococcal
      enterotoxin B (SEB) presentation to naive CD4+ T cells. RESULTS: The mean (SD)
      naive B cell (CD19+/CD27-) purity obtained from this two-step method compared
      with the one-step method was 97% (1.0) versus 90% (1.2), respectively. This two
      step method can be used with a sample of whole blood as small as 10 ml. The
      isolated naive B cells were phenotypically at a resting state and were able to
      prime naive CD4+ T cell activation by Staphylococcal enterotoxin B (SEB)
      presentation. CONCLUSIONS: This two-step non-flow cytometry-based approach
      improved the purity of isolated naive B cells compared with conventional one-step
      magnetic bead method. It also worked well with a small blood volume. In addition,
      this study showed that the isolated naive B cells can present a super-antigen
      "SEB" to activate naive CD4 cells. These methods may thus be useful for further
      in vitro characterization of human naive B cells and their roles as antigen
      presenting cells in various diseases.

PMID- 23156853
TI  - Multiplex PCR for identifying common dust mites species (Dermatophagoides
      pteronyssinus, Dermatophagoides farinae and Blomia tropicalis).
AB  - INTRODUCTION: Dust mites are known to be an important source of inhalant
      allergens causing allergic rhinitis and asthma worldwide. The sizes of dust mite
      populations in patients' houses are useful to monitor the risk of allergen
      exposure. However, mite identification using the conventional microscopic
      technique requires specific expertise and is time consuming; therefore a
      molecular technique has been developed in order to solve these drawbacks.
      OBJECTIVE: To develop a multiplex PCR assay for identifying the three common dust
      mite species in Thailand, namely Dermatophagoides pteronyssinus (Dp), D. farinae
      (Df) and Blomia tropicalis (Bt), and to evaluate the efficacy of the technique.
      METHODS: Pairs of primers were designed and tested in either singleplex PCR or
      multiplex PCR. The multiplex PCR technique was also optimized in order to obtain
      specific products. The reaction mixture contained 5 pmole of individual primers,
      10 mM dNTP, 5 units Taq DNA polymerase and genomic DNA (gDNA). The reaction was
      run for 25 cycles at 94 degrees C for 20 seconds, 58 degrees C for 20 seconds and
      72 degrees C for 30 seconds. The PCR products were analyzed by 1.5% agarose gel
      electrophoresis with GelRed fluorescence dye. The optimized multiplex technique
      was also tested with 30 house dust samples and dust samples spiked with DNA from
      other insect and mite species. RESULTS: Three PCR products were obtained with the
      relevant gDNA templates as expected; 143 bp for DF, 221 bp for DP and 318 bp for
      BT, respectively. The detection limit of the tests was found to be as low 1 ng of
      gDNA, whereas mixed gDNA species confirmed the 100% specificity of this assay.
      The total duration from the preparation of the PCR reaction mixture until the
      analysis by agarose gel electrophoresis was approximately 2 hours. No amplified
      product was obtained from mites and insects of other species. CONCLUSION: The
      multiplex PCR was successfully developed for identifying 3 common dust mite
      species. This technique can be helpful, not only for non-acarologist personnel
      for dust mite identification, but also for patients who are allergic to dust
      mites.

PMID- 23156854
TI  - Comparison of allergenic components and biopotency in whole body extracts of wild
      and laboratory reared American cockroaches, Periplaneta americana.
AB  - BACKGROUND AND OBJECTIVE: Most allergen extracts/vaccines used today in clinical
      practice are derived from natural allergen sources. Therefore, their allergic
      components may vary as these are prone to natural variation. This study aims to
      compare the allergenic components and biological potency of crude extracts from
      wild and laboratory reared American cockroaches. METHODS: Crude extracts of male
      and female of wild and laboratory reared American CR, were prepared by the same
      method. Their allergenic components were evaluated by in vitro assays such as
      protein contents, protein profiles, quantification of major allergens (Per a 1
      and Per a 9) and IgE inhibition ELISA assay. RESULTS AND DISCUSSION: There was no
      statistically significant difference between the protein contents and the
      concentrations of Per a 1 in the crude extracts from both groups. However, the
      Per a 9 levels in extracts of wild CR were significantly higher than those from
      the extracts of laboratory reared CR. The protein patterns of the extracts of
      laboratory reared CR exhibited more consistency in the number of bands with
      higher intensity than those of wild CR. Pooled extracts of laboratory reared CR
      could inhibit IgE binding to that of wild CR up to 78%. The endotoxin content of
      extracts of laboratory reared CR were ten times less than those of the the wild
      CR. We have successfully determined the allergenic potency of the extracts of
      laboratory reared CR versus those of the wild CRs by in vitro assays. Further
      studies should be performed to determine the biological potency of CR extracts by
      in vivo assays for clinical application. CONCLUSION: Our finding indicates that
      the laboratory reared CR would be the better source of material in vaccine
      production than the wild CR.

PMID- 23156855
TI  - Medullary ischemia due to vertebral arteritis associated with Behcet syndrome: a
      case report.
AB  - Here we report an extremely rare case of Behcet syndrome (BS) that showed acute
      onset of Wallenberg syndrome and was treated successfully by corticosteroids. A
      51-year-old woman with BS had a sudden onset of Wallenberg syndrome. Three days
      after the onset, she was transferred to our institute. In the magnetic resonance
      imaging (MRI) study on admission, T2-weighted and fluid-attenuated inversion
      recovery images showed a high intensity area in the left paramedian region of the
      medulla oblongata. Contrast-enhanced T1-weighted images showed enhancement in the
      vessel wall of the left vertebral artery. We diagnosed her as having Wallenberg
      syndrome due to the acute vertebral arteritis associated with BS. After
      initiation of high-dose steroid therapy, her symptoms gradually improved. Two
      months after admission, she was discharged from our institute with mild
      hemihypesthesia. We hypothesized that vertebral arteritis due to BS had caused
      hypoperfusion of the medullary perforators causing Wallenberg syndrome in our
      patient.

PMID- 23156856
TI  - Sodium nitroprusside and toxic epidermal necrolysis.
AB  - Sodium nitroprusside (SNP) is one of the most widely used parenteral
      antihypertensive agents in severe hypertension management. Toxic epidermal
      necrolysis (TEN) is a rare, mostly drug-induced, severe muco-cutoneous reaction
      with various complications and high mortality. A fifteen years old girl who is on
      hemodialysis for chronic renal insufficiency and was hospitalized for emergency
      management of hypertension, developed a diffuse maculopapular rash within minutes
      after SNP infusion. In 72 hours, approximately 40% of the body surface was
      involved with skin detachment indicating epidermal necrolysis and a skin biopsy
      confirmed the diagnosis of TEN. To the best of our knowledge there is no report
      of an association of SNP and TEN in the English literature and the clinical data
      exemplifying consequent IgE and non-IgE mediated hypersensitivity reactions are
      scanty. With this report we wanted to present a rare complication of SNP infusion
      indicating another rare occurrence of sequential IgE and non-IgE mediated
      hypersensitivity reactions.

PMID- 23156857
TI  - [Joint pain and swelling. What kind of tumor in the toe? Gout tophi].

PMID- 23156858
TI  - [Summer in the intensive care unit. Why did the patient get blisters on the
      abdomen? Miliaria cristallina].

PMID- 23156859
TI  - [2012 Nobel Prize in Medicine. Cellular rejuvenation for diversity].

PMID- 23156860
TI  - [New STIKO recommendations. Booster vaccinations may be used generously].

PMID- 23156861
TI  - [Emergency decision at the death bed. When should the defibrillator be shut
      off?].

PMID- 23156862
TI  - [German guidelines are overdue. When ICD's impede dying (interview by Dr. med.
      Jochen Aumiller)].

PMID- 23156863
TI  - [New diabetes guidelines in the EU and USA. Rigid HbA1c specifications are
      history!].

PMID- 23156864
TI  - [Heart and lung functioning normally. Where does the dyspnea come from?].

PMID- 23156865
TI  - [In CNS symptoms remember: sepsis is an encephalopathy!].

PMID- 23156866
TI  - [Investigative strategies in increased liver values. Necrosis or cholestasis?].

PMID- 23156867
TI  - [Effectiveness of phytochemicals. Broccoli in intestinal infections? (interview
      by Dr. Beate Schumacher)].

PMID- 23156868
TI  - [District level as kicker, but at the top in action].

PMID- 23156869
TI  - [Rehabilitation medications].

PMID- 23156870
TI  - [Abdomen in social network].

PMID- 23156871
TI  - [My student has a psychosis. How should I behave?].

PMID- 23156872
TI  - [Tinnitus and hearing loss. Can a cochlear implant help in this case?].

PMID- 23156873
TI  - [Renal denervation. How high is the rate of complications?].

PMID- 23156874
TI  - [No tumor in colonoscopy 2 years ago. Now the patient has a positive hemoccult
      test - how to proceed?].

PMID- 23156875
TI  - [Angiology is more than peripheral vascular disease].

PMID- 23156876
TI  - [Congenital vascular malformations].

PMID- 23156877
TI  - [Scarlet fever].

PMID- 23156878
TI  - [Problems in intravenous access in outpatient emergency? There are
      alternatives!].

PMID- 23156879
TI  - [Vaccinations for travelers].

PMID- 23156880
TI  - [Hypertension: most important risk factor of a stroke].

PMID- 23156881
TI  - [Migration and pain].

PMID- 23156882
TI  - [Chronic ischemic heart diseases. Effectively alleviating ischemia symptoms].

PMID- 23156883
TI  - [Relative improvement of the quality of life (interview by Philip Grazel)].

PMID- 23156884
TI  - [New fixed combination for asthma patients. Fluticasone plus formoterol - proven
      drugs for the first time in fixed combination].

PMID- 23156885
TI  - Damas hospital compliance to American College of Cardiology reperfusion therapy
      during acute ST-elevation myocardial infarction.
AB  - Despite improvements in care, up to one-third of patients presenting with ST
      elevation myocardial infarction (STEMI) within 12 hours of symptom onset receive
      no reperfusion therapy. Despite effective pre- and in-hospital reperfusion
      strategies becoming standard over the past two decades, time-to-admission and
      time-to-treatment remains prolonged. Prompt reperfusion treatment is essential to
      decrease mortality. The ACC/AHA guidelines recommend that the interval between
      arrival at the hospital and intracoronary balloon inflation during percutaneous
      coronary intervention should be within ninety minutes of patient arrival to the
      ED or less and within 30 minutes for fibrinolytic therapy. However, few hospitals
      meet this objective. We did a retrospective analysis of patients with STEMI from
      January 2008 to December 2010. From an initial list of 57 patients, only 45
      patients presented with confirmed STEMI. Of these, 35 had indication for
      reperfusion therapy. 97% received fibrinolytic therapy versus 3% who underwent
      percutaneous coronary intervention (PCI). The reperfusion time goal was achieved
      in 45% of cases treated with fibrinolytic therapy. Most of the patients
      presenting with STEMI undergo reperfusion therapy with fibrinolytic therapy. PCI
      was not performed as initial reperfusion therapy, even at regular duty hours.
      Reperfusion therapy was performed beyond the expected time goal in more that half
      of the cases. The most significant delay was related to nursing staff
      performance.

PMID- 23156886
TI  - Evaluation of a vancomycin dosing regimen for patients on high flux hemodialysis:
      an observational study.
AB  - Vancomycin is the mainstay antibiotic used in hemodialysis group due to high
      prevalence of methicillin resistant Staphylococcus Aureus. For years regimens of
      vancomycin in high flux hemodialysis (HFHD) patients were designed to achieve a
      pre-dialysis vancomycin concentration between 5-20 ug/mL. Recent guidelines
      increased the recommended pre-dialysis level to 15-20 ug/ml for health care
      associated infections, bacteremia and osteomyelitis. The purpose of this study
      was to determine if the loading dose (LD) before HFHD and the maintenance dose
      (MD) of vancomycin achieved a pre-dialysis concentration between 15-20 ug/ml on
      HFHD in-patients with a suspected infection. The second purpose was to predict an
      adequate vancomycin dosage to achieve the new recommended levels. MATERIAL AND
      METHODS: An observational prospective study on hospitalized adult patients on
      HFHD with evidence of infection treated with 1 gm LD of vancomycin and 500 mg MD.
      Plasma levels of vancomycin were measured before each HFHD for three consecutive
      times. Age, gender, weight at admission, blood flow rate, dialyzer flow rate,
      type of filter and HFHD length were evaluated. RESULTS: Twenty-one patients met
      the inclusion criteria. All of them were treated with 1 gm LD of vancomycin and
      500 mg MD protocol. The mean pre-dialysis concentration #1 was 10.8 ug/mL. The
      mean pre-dialysis concentration #2 was 13 ug/mL, and the mean pre-dialysis
      concentration #3 was 12 ug/mL. Only 36% of HFHD sessions achieved an adequate
      vancomycin level. A liner regression analysis predicted that a loading dose of 23
      mg/kg LD and 8 mg/kg MD achieved the recommended pre-dialysis vancomycin
      concentration. CONCLUSIONS: Current dose regimen of 1 gm LD and 500 mg MD of
      Vancomycin are not adequate to achieve recommended pre-dialysis level of 15-20
      ug/mL for health care associated infections, bacteremia and osteomyelitis in most
      patients on HFHD. Based on our statistical analysis, we recommended that 23 mg/kg
      of LD and 8 mg/kg of MD would achieve an adequate vancomycin level.

PMID- 23156887
TI  - Severe hypertriglyceridemia in Puerto Rico blood donors: a population study 2009
      2011.
AB  - Puerto Rico blood donor issues has been identified in cases of severe
      hypertriglyceridemia presenting as turbid. Blood donations resulting in milky
      serum must be discarded. They are discarded because we cannot properly test the
      donation. This is the first report where we correlate turbidity and
      cardiovascular risk factors in the Puerto Rico population as well as blood types
      O and A, Rh (+) with dyslipidemia. Blood donors should be screened in more
      details regarding cardiovascular and metabolic risks to avoid problems with
      recruitment and retention strategies.

PMID- 23156888
TI  - Outcomes of glycemic control in Hispanic geriatric diabetic patients admitted to
      a general ward community hospital in Puerto Rico.
AB  - BACKGROUND: Diabetes mellitus is one of the most prevalent medical conditions
      among the Hispanic population. Although studies with patients in intensive care
      units have shown poor outcomes among those with uncontrolled glucose, more recent
      data have shown increased mortality associated with a tighter inpatient glucose
      control. In view of the lack of information regarding geriatric Hispanic patients
      with diabetes this study evaluated the effect of glucose control in the outcomes
      of this population in a community hospital in Puerto Rico. METHODS: Through
      analysis of data from a previous study we evaluated 502 admissions of Hispanic
      geriatric patients with diabetes as comorbidity, for glucose control, management
      of diabetes and outcome. Data was stratified by age groups (65-74 years, 75-84
      years and > or = 85 years) and outcomes were compared between the groups using
      chi-square and odds ratio. RESULTS: The most common admission diagnosis was
      pneumonia. Hypoglycemia was the most common complication and was associated with
      tighter glucose control in the age group of 75-84 years. An increased risk of
      having an acute coronary syndrome/acute myocardial infarction among uncontrolled
      patients was observed in the 75-84 year old group. Finally, although we found a
      high prevalence of uncontrolled blood glucose, only 54% of the patients received
      interventions for their glucose control. CONCLUSIONS: Poor glucose control seems
      to be associated with a tendency for decreased risk of hypoglycemia and higher
      risk of acute coronary syndrome/acute myocardial infarction as complications
      among geriatric patients with diabetes admitted to a general ward.

PMID- 23156889
TI  - [Orbital tumors: experience with 35 cases].
AB  - Tumors of the orbit are pathology of considerable complexity in management due to
      the diverse anatomic and muscular, vascular, cartilagenous and neural components
      present. We review a series of 35 cases managed at the National Institute of
      Cancer in Bogota, Colombia. We determine variables such as age, sex, symptoms,
      histology, location and surgical procedure of these tumors. This review suggest
      that this complex pathology should be managed by a multidisciplinary team with
      extensive neurosurgical experience to obtain satisfactory results.

PMID- 23156890
TI  - Pulmonary metastasectomy for children with malignant tumors.
AB  - In children with primary solid malignant tumors the most frequent site of
      metastasis is usally the lung. Pulmonary metastasectomy is part of the standard
      of care in adult malignancies but its role in pediatric patients has been poor
      characterized. This review article discusses the benefits, outcomes according
      tumor histology, selection criteria, adjuvant therapies and surgical techniques
      employed in the resection of pulmonary metastases in children with malignant
      tumors.

PMID- 23156891
TI  - No asthma, no parasites is a rare type of leukemia: chronic myeloid neoplasm with
      eosinophilia and abnormality of platelet-derived growth factor receptor alpha.
AB  - Chronic myeloid neoplasm with eosinophilia and abnormality of platelet-derived
      growth factor receptor alpha (PDGFRA), referred as chronic eosinophilic leukemia,
      is an extremely rare neoplasm where long-term prognosis is uncertain though a
      high grade of responsiveness to Imatinib has been reported. The mortality and
      morbidity associated with chronic eosinophilic leukemia is associated with the
      degree of tissue involvement, damage, or both at diagnosis. We discuss a case of
      a young male patient with past medical history of hypoglycemia that presented to
      the emergency room with a complaints of a sharp abdominal pain localized in the
      upper quadrants. Laboratories were remarkable for elevated white blood cells with
      eosinophils predominance, anemia and thrombocytopenia. Bone marrow biopsy
      dislocated a FIP1L1-PDGFRA fusion gene chronic eosinophilic leukemia. Physicians
      need to have a high index of suspicion of this rare entity since not all
      eosinophilias can be interpreted as asthma or parasitis infections.

PMID- 23156892
TI  - Intrathoracic kidney in a child: case report and review of literature.
AB  - Intrathoracic ectopic kidney is a rare congenital abnormality with a prevalence
      estimated as less than one in 10000 and with only thirteen cases reported in the
      pediatric age group over the past twenty-five years. Herein, we report the
      uncommon case of a 20 month-old-male exhibiting a left ectopic intrathoracic
      kidney diagnosed as an incidental finding in image studies. Uncomplicated
      incidentals diagnosis has demonstrated normal function and development of those
      kidneys in long-term follow-up with no late bowel herniation.

PMID- 23156894
TI  - Synovial sarcoma of the hypopharynx in pregnancy.
AB  - Synovial sarcomas of the hypopharynx are a rare form of soft tissue sarcomas. In
      the head and neck, they are most commonly found on the pharyngeal wall in areas
      that do not have synovial cells. We review a case of a 23 year-old pregnant
      female who presented to our hospital with acute airway obstruction due to a large
      hypopharynx lesion. She underwent emergency tracheotomy and tumor debulking.
      Pathology revealed synovial sarcoma. After the procedure the patient went into
      labor delivering a 29 weeks premature child. Six weeks after being discharged
      from the hospital the patient had a partial pharyngectomy performed to excise the
      remnant base of the tumor. She has had no recurrence at the 30-month post
      operative period.

PMID- 23156893
TI  - Secondary biliary cirrhosis due to a rare choledochal cyst type II complicated
      with portal hypertension and pancytopenia in a young female patient.
AB  - Choledochal cyst type II, is an extremely rare cause of portal hypertension,
      severe pancytopenia in an adult patient, and a complication of long-standing
      disease. We present an uncommon cause of portal hypertension in a young female
      patient secondary to an obstructive choledochal cyst type II provoking massive
      splenomegaly and severe pancytopenia. A high level of clinical suspicion is
      important due to its high mortality rate if it remains undiagnosed. To our
      knowledge there are few publications describing this rare type of choledochal
      cyst in a Hispanic adult.

PMID- 23156895
TI  - [Rapidly progressive compromise of cranial pairs as neurosyphilis manifestation].
AB  - Syphilis remains a common disease throughout the world, being neurosyphilis a
      relatively common manifestation. A case of a 34 years old male with HIV and
      neurosyphilis is presented, characterized by a clinical course evidenced by
      progressive palsy of cranial nerves. This case is unusual and a rare presentation
      of progressive cranial involvement with swallowing deficit, have found no similar
      data in the literature.

PMID- 23156896
TI  - Immuno compromised patients: what a challenge!
AB  - Mucormycosis is an uncommon but fatal fungal infection of airborne transmission.
      Its is usually seen in immunocompromised patients including diabetics,
      malignancies, transplant patients and renal insufficiency. We review the case of
      an immunocompromised patient unresponsive to broad-spectrum antibiotics and
      conventional antifungal therapy with lung mucormycosis.

PMID- 23156897
TI  - Relational learning in glaucous-winged gulls (Larus glaucescens).
AB  - An experimental approach was created for the comparative investigation of the
      cognitive abilities of the glaucous-winged gull (Larus glaucescens) in their
      natural habitat. The territoriality of gulls during the breeding period and the
      fact that the gulls inhabiting the territory of the Komandorsky Reserve are
      practically not in fear of humans allowed us to work with individually recognized
      birds directly at their nest sites inside the colony. The possibility of using
      this approach to investigate their cognitive abilities was demonstrated on 24
      gulls, in particular, to investigate their abilities for relative size
      generalization. The first experiment illustrated that the gulls are able to learn
      to discriminate two pairs of stimuli according to the feature: 'larger' or
      'smaller'. They were then given a test to transfer the discriminative rule in
      which novel combinations of the same stimuli were used. The gulls successfully
      coped with only a few of these tests. In the next experiment the birds were
      taught to discriminate four pairs of similar stimuli. The majority of the birds
      coped with the tests to transfer the discriminative rule both to the novel
      combinations of familiar stimuli, and also to the novel stimuli of the familiar
      category (items of different colour and shape). However, none of the birds
      transferred the discriminative rule to stimuli of a novel category (sets
      differing by number of components). Thus, in their ability to generalize at a
      preconceptual level gulls are more comparable with pigeons, whereas large-brained
      birds (crows and parrots), are capable of concept formation.

PMID- 23156898
TI  - Working memory capacity and mental rotation: evidence for a domain-general view.
AB  - Despite the existence of numerous studies that examined the relationship between
      working memory capacity and performance in complex cognitive tasks, it remains
      unclear whether this capacity is domain specific or domain general. In addition,
      the available empirical evidence is somewhat contradictory. In this work we have
      studied the role of verbal working memory capacity in a non-verbal task--mental
      image rotation. If this capacity were domain specific it would be expected that
      high and low verbal span participants would obtain similar results in the mental
      rotation task. We have found that this is not the case as the high span
      participants performed better in terms of both speed and accuracy. Moreover,
      these differences depended on the processing component of the mental rotation
      task: the higher the processing requirements the higher the differences as a
      function of the working memory capacity. Therefore, the evidence presented here
      supports the domain general hypothesis.

PMID- 23156899
TI  - Masked and unmasked priming effects as a function of semantic relatedness and
      associative strength.
AB  - The study presented in this paper aimed to investigate the pattern of semantic
      priming effects, under masked and unmasked conditions, in the lexical decision
      task, manipulating type of semantic relation and associative strength. Three
      different kinds of word relations were examined in two experiments: only
      semantically related words [e.g., codo (elbow)-rodilla (knee)] and
      semantic/associative related words with strong [e.g., mesa (table)-silla (chair)
      and weak association strength [e.g., sapo (toad)-rana (frog)]. In Experiment 1 a
      masked priming procedure was used with a prime duration of 56 ms, and in
      Experiment 2, the prime was presented unmasked for 150 ms. The results showed
      that there were masked priming effects with strong associates, but no evidence of
      these effects was found with weak associates or only-semantic related word pairs.
      When the prime was presented unmasked, the three types of relations produced
      significant priming effects and they were not influenced by association strength.

PMID- 23156900
TI  - The role of perceptual information in familiarity-based scene recognition.
AB  - A method to analyze the role of familiarity in recognizing pictures of everyday
      scenes is introduced. The idea is to manipulate two within-subjects conditions:
      an experimental condition where the scenes repeat perceptual information (e.g.
      buildings and/or vehicles) and a control condition. The results show the two
      conditions did not differ in terms of hit rates, but in the experimental
      condition there were significantly fewer false alarms, yielding better results,
      which supports the findings of past research studies that have used verbal
      materials. This perceptual facilitation was maintained throughout a week-long
      retention interval. Finally, a detailed analysis of this facilitation shows it
      was due to a significant reduction in false alarms on know judgments, emphasizing
      familiarity's role in explaining this effect.

PMID- 23156901
TI  - Aversive priming: cognitive processing of threatening stimuli is facilitated by
      aversive primes.
AB  - It would be reasonable to expect that our previous experience regarding a
      stimulus that predicts harm would make the subsequent identification of that
      stimulus easier when harm happens again. Forty-eight volunteers were submitted to
      both phases of this sequence of events: learning of the predictive relationship
      and later priming. A face with neutral expression (CS+) was paired with a
      moderately aversive electric shock and another (CS-) with a neutral tone.
      Subsequently, these two faces, as well as other known and new faces, were
      presented for familiarity judgments. Both the CS+ and the CS- faces were preceded
      by an aversive stimulus (aversive prime) in one occasion and by a neutral
      stimulus (neutral prime) in another. The familiarity judgment regarding the CS+
      was faster after the aversive prime than after the neutral prime, but there was
      no difference regarding the CS-. The differential effect of the aversive prime
      over the CS+ and the CS- showed a significant but small correlation with the
      differential skin conductance response to CS+ and CS- (signal learning), and with
      the differential evaluation of those stimuli in terms of like-dislike (evaluative
      learning). The scope of these results, as well as the usefulness of this
      methodological model, is discussed.

PMID- 23156902
TI  - Impulsivity, intelligence, and discriminating reinforcement contingencies in a
      fixed-ratio 3 schedule.
AB  - Research conducted in academic contexts suggests a moderating effect of impulsive
      behavior on the relationship between aptitude and achievement. According to these
      studies, intelligence scores being equal, higher levels of impulsivity have an
      adverse effect on achievement (Helmers, Young, & Pihl, 1995; Vigil-Colet &
      Morales-Vives, 2005; Zeidner, 1995). The present study aims to contrast the
      aforementioned moderator effect in the context of a discriminant learning task,
      carried out under a fixed-ratio 3 reinforcement schedule. To that end, an
      impulsive behavioral pattern was identified in a sample of 1,600 participants'
      task execution based on response rate and latency. Said pattern was consistent
      and stable across several trials and can be ascribed to subjects' interactive
      style (Hernandez, 2000). The observed interaction effect supports the hypothesis
      that impulsivity has a moderating effect on the aptitude-achievement
      relationship, highlighting how it impacts achievement differentially depending on
      the subject's level of aptitude.

PMID- 23156903
TI  - Clinical efficacy of a new automated hemoencephalographic neurofeedback protocol.
AB  - Among the ongoing attempts to enhance cognitive performance, an emergent and yet
      underrepresented venue is brought by hemoencefalographic neurofeedback (HEG).
      This paper presents three related advances in HEG neurofeedback for cognitive
      enhancement: a) a new HEG protocol for cognitive enhancement, as well as b) the
      results of independent measures of biological efficacy (EEG brain maps) extracted
      in three phases, during a one year follow up case study; c) the results of the
      first controlled clinical trial of HEG, designed to assess the efficacy of the
      technique for cognitive enhancement of an adult and neurologically intact
      population. The new protocol was developed in the environment of a software that
      organizes digital signal algorithms in a flowchart format. Brain maps were
      produced through 10 brain recordings. The clinical trial used a working memory
      test as its independent measure of achievement. The main conclusion of this study
      is that the technique appears to be clinically promising. Approaches to cognitive
      performance from a metabolic viewpoint should be explored further. However, it is
      particularly important to note that, to our knowledge, this is the world's first
      controlled clinical study on the matter and it is still early for an ultimate
      evaluation of the technique.

PMID- 23156904
TI  - Comparison of neuropsychological performance between students from public and
      private Brazilian schools.
AB  - Neuropsychological assessment reveals that certain cognitive changes that take
      place during the neural development process may be associated with
      biopsychosocial issues. A substantial body of research has focused on cognitive
      development in children and adults, but few such studies have been carried out on
      adolescents. Therefore, research into the processing of neuropsychological
      functions in adolescents, taking into account the role of major socio-cultural
      factors such as school type (public vs. private), is highly relevant. The present
      study sought to assess whether differences in neuropsychological development
      exist between adolescent students of public (government-funded) and private
      schools. A total of 373 grade-matched students between the ages of 12 and 18, 190
      from public schools and 183 from private schools, took part in the study. All
      subjects had no self-reported neurologic or psychiatric conditions and sensory
      disorders. The NEUPSILIN Brazilian Brief Neuropsychological Assessment Battery
      was administered to this sample. Comparison of mean scores (one-way ANCOVA with
      socioeconomic score and age as covariates) showed that adolescents attending
      private schools generally outperformed their public-school peers in tasks
      involving sustained attention, memory (working and visual), dictated writing, and
      constructional and reflective abilities. We conclude that school type should be
      taken into account during standardization of neuropsychological assessment
      instruments for adolescent and, probably, child populations.

PMID- 23156905
TI  - Symbolic and non-symbolic number magnitude processing in children with
      developmental dyscalculia.
AB  - The aim of this study was to evaluate if children with Developmental Dyscalculia
      (DD) exhibit a general deficit in magnitude representations or a specific deficit
      in the connection of symbolic representations with the corresponding analogous
      magnitudes. DD was diagnosed using a timed arithmetic task. The experimental
      magnitude comparison tasks were presented in non-symbolic and symbolic formats.
      DD and typically developing (TD) children showed similar numerical distance and
      size congruity effects. However, DD children performed significantly slower in
      the symbolic task. These results are consistent with the access deficit
      hypothesis, according to which DD children's deficits are caused by difficulties
      accessing magnitude information from numerical symbols rather than in processing
      numerosities per se.

PMID- 23156906
TI  - Executive attention and personality variables in patients with frontal lobe
      damage.
AB  - Executive Control is required to deal with novel situations or when an action
      plan is needed. This study aimed to highlight the executive attention deficits of
      patients with frontal lobe damage. To do so, the ANT-I task (Attention Network
      Test-Interactions) was administered for the first time to a group of 9 patients
      with frontal damage caused by traumatic brain injury (TBI) and a matched control
      group. This task made it possible to measure the three attentional networks
      proposed by Posner and Dehaene (1994) and their interactions. Results on the
      alerting and orienting networks did not show any significant differences between
      the groups. However, a significant effect of group on the executive control
      network was observed. In addition, participants' personality was assessed with a
      clinical inventory (the Millon Personality Inventory) that showed a significant
      positive correlation between borderline personality disorder and the conflict
      index. These results suggest that frontal lobe damage causes an exclusive
      impairment in the conflict resolution network that is related to personality
      traits characterized by a lack of behavioral control. More research will be
      necessary to study this causal relationship.

PMID- 23156907
TI  - Infant crying: pattern of weeping, recognition of emotion and affective reactions
      in observers.
AB  - This study has three objectives: a) to describe the main differences in the
      crying patterns produced by the three affective states most closely related to
      crying: fear, anger and pain; b) to study the adults' accuracy in the recognition
      of the affective states related to the infant's crying, and c) to analyze the
      emotional reaction that infant crying elicits in the observers. Results reveal
      that the main differences appear in the ocular activity and in the pattern of
      weeping. The infants maintain their eyes open during the crying produced by fear
      and anger, but in the case of crying provoked by painful stimuli, the eyes remain
      closed almost all the time. In regard to the pattern of weeping, the crying
      gradually increase in the case of anger, but the weeping reaches its maximum
      intensity practically from the beginning in the case of pain and fear. In spite
      of these differences, it is not easy to know the cause that produces crying in
      infants, especially in the case of fear or anger. Although observers can't
      recognize the cause of crying, the emotional reaction is greater when the baby
      cries in pain than when the baby cries because of fear or anger.

PMID- 23156908
TI  - Profiles of maternal care observed in a group of Brazilian mothers: an
      exploratory study.
AB  - The aim of this study is to characterize profiles of maternal care in a sample of
      Brazilian mothers, using a cultural-biological perspective. Participants were 315
      women who had at least one child younger than six years-old. They were selected
      from six Brazilian states. In each state, two groups of mothers were studied, one
      from the capital and one from a small city. They were interviewed and answered
      scales on allocentrism, social support, adult attachment, and practices of
      childcare. Mothers' characteristics, the type of context (capital vs. small
      city), and reported childcare practices were used in a Tree analysis. A
      Correspondence analysis was performed using the four clusters obtained and
      mothers' answers regarding their youngest child. Univariate GLM analyses were
      performed to compare mothers in the four clusters in terms of their scores on the
      different scales. Four maternal profiles presenting distinctive patterns of
      association between mothers' characteristics and care practices displayed to the
      youngest child were identified. We conclude that maternal care is a multi
      determined phenomenon and that the method employed in this study can give
      insights into how the combination of diverse social-biological factors can result
      in a set of childcare practices.

PMID- 23156909
TI  - Attachment, emotion regulation and coping in Portuguese emerging adults: a test
      of a mediation hypothesis.
AB  - Although the quality of parent-adolescent emotional bonds has consistently been
      proposed as a major influence on young adult's psycho-emotional functioning, the
      precise means by which these bonds either facilitate or impede adaptive coping
      are not well-understood. In an effort to advance this inquiry, the present study
      examined interrelationships among measures of parental attachment, emotion
      regulation processes, and preferred coping strategies within a sample of 942
      college freshmen. Structural Equation Modelling was used to test whether the link
      between attachment to parents and the use of particular coping strategies is
      mediated by differences in emotion regulation mechanisms. As hypothesized,
      differences in attachment to parents predicted differences in the use of emotion
      regulation mechanisms and coping strategies. More specifically, having a close
      emotional bond, feeling supported in autonomy processes and having (moderately)
      low levels of separation anxiety toward parents predict more constructive emotion
      regulation mechanisms and coping strategies. Additionally emotion regulation was
      found to (partly or totally) mediate the association between attachment and
      coping.

PMID- 23156910
TI  - Emotional and social problems in adolescents from a gender perspective.
AB  - The present study aims to analyze the relationships between community
      involvement, perception of family and school climate, and emotional and social
      problems in adolescents (satisfaction with life, non-conformist social
      reputation, and school violence). The sample was composed of 1884 (52% boys and
      48% girls) adolescents aged from 11 to 17 years old (M = 13.7, SD = 1.4) from the
      Valencia Community and Andalusia. A structural equation model was calculated to
      analyze the data. The results indicated that adolescent community involvement was
      associated with positive perceptions of family and school climate, and school
      violence. Associations between the variables of the study included in the
      structural model were also analyzed as a function of gender. The relationship
      between school climate and social reputation was significant only for boys.
      Likewise, the association between community involvement and violent behavior was
      found to be significant only for boys. Finally, the results and their possible
      implications are discussed.

PMID- 23156911
TI  - Substance use in Portuguese and Spanish adolescents: highlights from differences,
      similarities and moderating effects.
AB  - Many behaviors with lasting health impact are initiated in adolescence. Substance
      use is one such behavior. To analyse the factors involved in adolescent substance
      use among Portuguese and Spanish boys and girls, an explanatory model was
      developed using structural equations modelling. The model proposes that the
      impact of social contexts (family, friends, classmates and teachers) on substance
      use (tobacco, alcohol and illicit drugs) is mediated by perceptions of well-being
      (psychological symptoms, well-being and school satisfaction). Data on 1589
      Portuguese (mean age = 13.27, SD = .59) and 4191 Spanish adolescents (mean age =
      13.21; SD = .47) who took part in the HBSC/WHO survey were analysed. The model
      fits the data of each country (CFI > .90; RMSEA < .03) and the majority of the
      relationships proposed in the model have been as expected for both samples. The
      relations with a major effect, for both countries, were: the negative effect of
      family on psychological symptoms and the positive effect of family on subjective
      well-being; the negative effect of classmates on psychological symptoms; the
      positive effect of teachers on school satisfaction; the effect of psychological
      symptoms (negative) and school satisfaction (positive) on well-being; the
      negative effect of school satisfaction on tobacco and alcohol use; and the
      positive effect of tobacco on alcohol use, and alcohol use on cannabis. For each
      of the dependent factors studied (tobacco, alcohol and illicit drugs), the levels
      of explained variance varied between 9% (for tobacco use) and 46% (for alcohol
      use). Some non-invariant paths were obtained in country comparisons, controlling
      for gender. In multivariate analyses the paths from tobacco use to cannabis and
      from alcohol to cannabis were significant, but much stronger for Spanish girls
      than Portuguese girls.

PMID- 23156912
TI  - Effect of different professions' clothing on children's height perception.
AB  - Height is a biological factor that can affect how others perceive and behave
      toward an individual. Height is a biological factor that can affect how others
      perceive and behave toward an individual. Clothing, as a non-biological factor,
      can affect these perceptions of height. In this study weClothing, as a non
      biological factor, can affect these perceptions of height. In this study we
      investigated the effect of different professions' clothing on children's
      perceptions of height. One investigated the effect of different professions'
      clothing on children's perceptions of height. One hundred and eighty primary
      school students participated in this study and estimated the height of an actor
      in the clothing of four different professions which differed in terms of
      prestige. The results of study showed that the difference between the perceived
      and actual height was larger when participants estimated the height of socially
      esteemed professions. Also there was no difference between girls' and boys'
      estimation of different professions' height. The implications of these findings
      are discussed.

PMID- 23156913
TI  - Academic goal profiles: a comparison of blind and sighted students.
AB  - Based on academic goal theory, we compared the goals of visually impaired and
      sighted students. Participants included 171 students affiliated with ONCE (the
      National Spanish Organization for the Blind) and 163 sighted students, ranging
      from 8 to 27 years of age, who responded to the Spanish adaptation (Gonzalez,
      Torregrosa, & Navas, 2002) of the goals questionnaire created by Hayamizu, Ito,
      and Yohiazaki (1989) and Hayamizu and Weiner (1991). Factor analysis indicated
      that goals varied among these students and that new ones arose in this study;
      furthermore, the model remained invariable regardless of students' status
      (visually impaired versus sighted). Cluster analysis revealed three distinct
      profiles in terms of academic goals, while discriminant function analysis
      suggested these profiles vary as a function of students' status (visually
      impaired versus sighted). It seems that visually impaired students hold more
      learning-oriented academic goals.

PMID- 23156914
TI  - Academic effects of the Prestige oil spill disaster.
AB  - The effect of a large scale oil spill disaster on the academic achievement and
      classroom behavior of children and adolescents who lived on the Galician coast
      (Spain) is studied from an ecological perspective. 430 participants divided into
      three age groups of 5, 10, and 15 years of age, were studied. The participants
      came from three areas differently affected by the disaster. Dependent variables
      were academic achievement and classroom behavior of the participants after the
      Prestige disaster. Degree of exposure and other protective or risk factors were
      investigated as well. Repeated measures ANOVA to assess the main effects of the
      oil spill and hierarchical regression analyses to assess the contribution of the
      protective/vulnerability factors were performed. The results indicate that the
      effects of the disaster were relatively scarce. Some protective factors accounted
      for a certain degree of variance of different schoolroom behaviors. These results
      point to the intervention of protective factors in the adaptation to the
      disaster.

PMID- 23156916
TI  - A correlational and predictive study of creativity and personality of college
      students.
AB  - The goals of this study were to examine the relationship between creativity and
      personality, to identify what personality variables better predict creativity,
      and to determine whether significant differences exist among them in relation to
      gender. The research was conducted with a sample of 87 students at the
      Universidad Publica de Navarra, Spain. We administered the Creative Intelligence
      Test (CREA), which provides a cognitive measure for creativity and the
      Situational Personality Questionnaire (SPQ), which is composed of 15 personality
      features. Positive and significant correlations between creativity and
      independence, cognitive control, and tolerance personality scales were found.
      Negative and significant correlations between creativity and anxious, dominant,
      and aggressive personalities were also found. Moreover, four personality
      variables that positively predicted creativity (efficacy, independence, cognitive
      control, and integrity-honesty) and another four that negatively predicted
      creativity (emotional stability, anxiety, dominance, and leadership) were
      identified. The results did not show significant differences in creativity and
      personality in relation to gender, except in self-concept and in social
      adjustment. In conclusion, the results from this study can potentially be used to
      expand the types of features that support creative personalities.

PMID- 23156915
TI  - Motivational and emotional profiles in university undergraduates: a self
      determination theory perspective.
AB  - Previous research has focused on specific forms of self-determined motivation or
      discrete class-related emotions, but few studies have simultaneously examined
      both constructs. The aim of this study on 472 undergraduates was twofold: to
      perform cluster analysis to identify homogeneous groups of motivation in the
      sample; and to determine the profile of each cluster for emotions and academic
      achievement. Cluster analysis configured four groups in terms of motivation:
      controlled, autonomous, both high, and both low. Each cluster revealed a distinct
      emotional profile, autonomous motivation being the most adaptable with high
      scores for academic achievement and pleasant emotions and low values for
      unpleasant emotions. The results are discussed in the light of their implications
      for academic adjustment.

PMID- 23156917
TI  - Coping strategies: gender differences and development throughout life span.
AB  - Development during life-span implies to cope with stressful events, and this
      coping may be done with several strategies. It could be useful to know if these
      coping strategies differ as a consequence of personal characteristics. This work
      uses the Coping with Stress Questionnaire with this aim using a sample of 400
      participants. Specifically, the effects of gender and age group (young people,
      middle age and elderly), as well as its interaction on coping strategies is
      studied. With regard to age, on one hand, it is hypothesised a decrement in the
      use of coping strategies centred in problem solving and social support seeking as
      age increases. On the other hand, the use of emotional coping is hypothesised to
      increase with age. With respect to gender, it is hypothesised a larger use of
      emotional coping and social support seeking within women, and a larger use of
      problem solving within men. A MANOVA found significant effects for the two main
      effects (gender and age) as well as several interactions. Separate ANOVAs allowed
      us to test for potential differences in each of the coping strategies measured in
      the CAE. These results partially supported the hypotheses. Results are discussed
      in relation to scientific literature on coping, age and gender.

PMID- 23156918
TI  - The impact of helping behavior on outgroup infrahumanization.
AB  - Infrahumanization research has verified that in intergroup contexts, there is a
      strong tendency to attribute secondary emotions, which are uniquely human, to the
      ingroup, while limiting that attribution in outgroups. Experiments have shown it
      to be as common as ingroup bias. However, it is not yet known what
      characteristics may mitigate this trend. This paper presents two studies. The
      first analyzes the impact of helping behavior on attributions of human traits to
      two fictitious groups. The second study's objective was to determine if members
      of the Spanish ingroup would infrahumanize an Ethiopian outgroup less when that
      outgroup performs prosocial behavior towards another group. Infrahumanization was
      determined by a lexical decision task, using the names of ingroup and outgroup
      members as priming. The results demonstrate that describing a fictitious group in
      altruistic terms increases their human profile (experiment one) and reduces
      infrahumanization (experiment two).

PMID- 23156919
TI  - Are they animals or machines? Measuring dehumanization.
AB  - The present research deals with two forms of dehumanization: 1) denying uniquely
      human attributes to others (seeing them as animals); 2) denying human nature to
      others (seeing them as machines or automata). Studies 1 and 2 explored these two
      forms of dehumanization, analyzing whether people associated their ingroup more
      with human-related words (vs. animal- vs. machine-related words) than two
      different outgroups. A paper and pencil procedure was used to find out which
      words were associated with the surnames of the ingroup (Spaniards) or the
      outgroup (Germans, Gypsies). Results showed that participants were more ready to
      link ingroup than outgroup surnames to human words. They also linked more Gypsy
      surnames to animal-related words and German surnames with machine-related words.
      Studies 3 and 4 used the Implicit Association Test to analyze the same ideas and
      replicated the results of Studies 1 and 2.

PMID- 23156920
TI  - The dark and bright sides of self-efficacy in predicting learning, innovative and
      risky performances.
AB  - The objective of this study is to analyze the different role that efficacy
      beliefs play in the prediction of learning, innovative and risky performances. We
      hypothesize that high levels of efficacy beliefs in learning and innovative
      performances have positive consequences (i.e., better academic and innovative
      performance, respectively), whereas in risky performances they have negative
      consequences (i.e., less safety performance). To achieve this objective, three
      studies were conducted, 1) a two-wave longitudinal field study among 527
      undergraduate students (learning setting), 2) a three-wave longitudinal lab study
      among 165 participants performing innovative group tasks (innovative setting),
      and 3) a field study among 228 construction workers (risky setting). As expected,
      high levels of efficacy beliefs have positive or negative consequences on
      performance depending on the specific settings. Unexpectedly, however, we found
      no time x self-efficacy interaction effect over time in learning and innovative
      settings. Theoretical and practical implications within the social cognitive
      theory of A. Bandura framework are discussed.

PMID- 23156921
TI  - Dynamic criteria: a longitudinal analysis of professional basketball players'
      outcomes.
AB  - This paper describes the fluctuations of temporal criteria dynamics in the
      context of professional sport. Specifically, we try to verify the underlying
      deterministic patterns in the outcomes of professional basketball players. We use
      a longitudinal approach based on the analysis of the outcomes of 94 basketball
      players over ten years, covering practically players' entire career development.
      Time series were analyzed with techniques derived from nonlinear dynamical
      systems theory. These techniques analyze the underlying patterns in outcomes
      without previous shape assumptions (linear or nonlinear). These techniques are
      capable of detecting an intermediate situation between randomness and
      determinism, called chaos. So they are very useful for the study of dynamic
      criteria in organizations. We have found most players (88.30%) have a
      deterministic pattern in their outcomes, and most cases are chaotic (81.92%).
      Players with chaotic patterns have higher outcomes than players with linear
      patterns. Moreover, players with power forward and center positions achieve
      better results than other players. The high number of chaotic patterns found
      suggests caution when appraising individual outcomes, when coaches try to find
      the appropriate combination of players to design a competitive team, and other
      personnel decisions. Management efforts must be made to assume this uncertainty.

PMID- 23156922
TI  - A comparative study on entrepreneurial attitudes modeled with logistic regression
      and Bayes nets.
AB  - Entrepreneurship research is receiving increasing attention in our context, as
      entrepreneurs are key social agents involved in economic development. We compare
      the success of the dichotomic logistic regression model and the Bayes simple
      classifier to predict entrepreneurship, after manipulating the percentage of
      missing data and the level of categorization in predictors. A sample of
      undergraduate university students (N = 1230) completed five scales (motivation,
      attitude towards business creation, obstacles, deficiencies, and training needs)
      and we found that each of them predicted different aspects of the tendency to
      business creation. Additionally, our results show that the receiver operating
      characteristic (ROC) curve is affected by the rate of missing data in both
      techniques, but logistic regression seems to be more vulnerable when faced with
      missing data, whereas Bayes nets underperform slightly when categorization has
      been manipulated. Our study sheds light on the potential entrepreneur profile and
      we propose to use Bayesian networks as an additional alternative to overcome the
      weaknesses of logistic regression when missing data are present in applied
      research.

PMID- 23156923
TI  - Reciprocity of temporary and permanent workers: an exploratory study in an
      industrial company.
AB  - The increasing use of temporary work prompts the need to understand to what
      degree workers with this type of contract differ from permanent workers as to the
      relationship they establish with the organization they work for. This study used
      a sample of temporary workers (N = 78) and permanent workers (N = 196) within the
      same company of electronics in Portugal. The results show that, regardless of the
      type of contract, the perception of human resource practices was related to the
      perception of psychological contract fulfillment by the company. Additionally and
      according to the norm of reciprocity, we verified that when workers thought the
      company was fulfilling its obligations they responded favorably showing more
      affective commitment towards the company. However, we found differences between
      these two groups of workers: for the permanent performance appraisal, training
      and rewards were human resources practices that were significantly related to
      psychological contract fulfillment, while for the temporary ones there weren't
      any specific practices that had a significant relationship with that variable.
      The practical implications of these findings for the management of temporary
      workers are discussed.

PMID- 23156924
TI  - The roles of constraint-based and dedication-based influences on user's continued
      online shopping behavior.
AB  - The objective of this study was to determine empirically the role of constraint
      based and dedication-based influences as drivers of the intention to continue
      using online shopping websites. Constraint-based influences consist of two
      variables: trust and perceived switching costs. Dedication-based influences
      consist of three variables: satisfaction, perceived usefulness, and trust. The
      current results indicate that both constraint-based and dedication-based
      influences are important drivers of the intention to continue using online
      shopping websites. The data also shows that trust has the strongest total effect
      on online shoppers' intention to continue using online shopping websites. In
      addition, the results indicate that the antecedents of constraint-based
      influences, technical bonds (e.g., perceived operational competence and perceived
      website interactivity) and social bonds (e.g., perceived relationship investment,
      community building, and intimacy) have indirect positive effects on the intention
      to continue using online shopping websites. Based on these findings, this
      research suggests that online shopping websites should build constraint-based and
      dedication-based influences to enhance user's continued online shopping behaviors
      simultaneously.

PMID- 23156925
TI  - Social integration of Latin-American immigrants in Spain: the influence of the
      community context.
AB  - The main goal of this study is to analyze the degree to which several community
      elements such as insecurity, discrimination and informal community support might
      have an influence on the social integration of Latin-American immigrants, a group
      at risk of social exclusion in Spain. Multivariate linear regression analyses
      results showed that informal community support is positively related to social
      integration whereas insecurity is negatively related. The statistical
      relationship between discrimination and social integration disappears once levels
      of informal community support are taken into account. A better understanding of
      the factors that either promote or inhibit the social integration progress of
      immigrant population is important to orientate public policies and intervention
      programs that contribute to the adaptation of this population to the host
      society.

PMID- 23156926
TI  - Language use and stereotyping: the role of approach and avoidance motivation
      goals.
AB  - The use of more abstract language to describe expected behaviors as opposed to
      unexpected behaviors has traditionally been considered a way of stereotype
      maintenance. This tendency is known as linguistic expectancy bias. Two
      experiments examined the influence of approach and avoidance motivational
      orientations on the production of this linguistic expectancy bias. It was
      predicted that approach strategic orientation is likely to describe expectancy
      consistent behaviors at a higher level of linguistic abstraction than expectancy
      inconsistent behaviors. In contrast, avoidance strategic orientation is likely to
      describe both expectancy consistent behaviors and expectancy inconsistent
      behaviors at a lower level of linguistic abstraction, thus facilitating the
      disappearance of linguistic expectancy bias. Two experiments confirmed these
      expectations, using strategic orientation manipulations based either on
      communication goals or on motor action, and measuring linguistic abstraction
      either on forced-choice answer format or on free descriptions. Implications for
      the generalisation of linguistic expectancy bias are discussed.

PMID- 23156927
TI  - On methods of access to the structure of social representations: the example of
      Europe.
AB  - The aim of this study is to identify the logic behind a range of statistical
      methods used to reveal the structure of social representations. Subjects (N =
      317) were asked to answer the following question: "For each category of European
      person, please indicate which other European he would most like to have contact
      with". The results of the similarity analysis lead us to the conclusion that
      there is an ethnocentric bias, and reveal the central factor of the
      representation. The representation obtained by factorial correspondence analysis
      seems closer to current reality and enables us to understand the divisions that
      have structured Europe and remained embedded in the subjects. Thus, the choice of
      analytical method is not merely anecdotal, given that representations obtained
      from the same data can vary immensely.

PMID- 23156928
TI  - Social representations, correspondence factor analysis and characterization
      questionnaire: a methodological contribution.
AB  - The characterization questionnaire is inspired by Q-sort methodologies (i.e.
      qualitative sorting). It consists in asking participants to give their opinion on
      a list of items by sorting them into categories depending on their level of
      characterization of the object. This technique allows us to obtain distributions
      for each item and each response modality (i.e. characteristic vs. not chosen vs.
      not characteristic). This contribution intends to analyze these frequencies by
      means of correspondence factor analysis. The originality of this contribution
      lies in the fact that this kind of analysis has never been used to process data
      collected by means of this questionnaire. The procedure will be detailed and
      exemplified by means of two empirical studies on social representations of the
      good wine and the good supermarket. The interests of such a contribution will be
      discussed from both methodological points of view and an applications
      perspective.

PMID- 23156929
TI  - Degree of proximity in the construction of social representations: the case of
      intelligence.
AB  - The present article is devoted to the empirical endeavor of studying the effect
      of the degree of proximity, defined by specific socio-educational insertions, on
      the organization of social representations of intelligence. A questionnaire was
      answered by a sample of 752 participants belonging to five different social
      categories with different degrees of proximity and knowledge about intelligence:
      mothers, fathers, mother-teachers and non-parent students (psychology and science
      students). The questionnaire included different topics, namely concerning the
      concept of intelligence, its development and the effectiveness of teaching
      procedures. Results show that the principles organizing the contents of
      representations are linked to the personal involvement in intelligence, on which
      subjects more or less implied take different positions. Results produced suggest,
      therefore, that the content of representations is directly linked to the
      activation of social roles and the salience of the object, reflecting the
      functional character that the organization of representations has to specific
      social dynamics.

PMID- 23156930
TI  - Dispositional optimism is unidimensional or bidimensional? The Portuguese revised
      Life Orientation Test.
AB  - The aim of the study is to adapt and then discuss the appropriateness of the Life
      Orientation Test as a one or two dimension scale. The research includes two
      studies; one is composed of a sequential sample of 280 people with multiple
      sclerosis, 71% female, and another includes a convenience sample of 615
      individuals from the community, 51.1% female. Because the construct is built upon
      a theoretical assumption that has one dimension, we examine the hypothesis of one
      or two factor solutions through confirmatory factor analysis, and the two
      dimension solution premise demonstrates better adjustment for both samples. The
      other psychometric properties explored show appropriate results for the
      Portuguese sample, and similar to the original ones; the Test therefore seems
      appropriate for use in cross cultural studies. Based on our results, we discuss
      whether the questionnaire is a one or two dimension instrument, concluding that
      it appears appropriate to accept the recommendations of the original authors to
      use it as a one-dimensional tool and, when necessary, to use both dimensions.

PMID- 23156931
TI  - Personality traits and sick leave in workers diagnosed with nonorganic neck pain.
AB  - Previous research has suggested that personality can influence the perception and
      reporting of physical symptoms, such as pain. To assess the relationship between
      the course of nonorganic neck pain and the individual's personality, we studied
      the association between two indicators of neck pain prognosis, such as the
      duration of sick leave associated with neck pain and sick leave recurrence, and
      15 personality traits in a sample of 64 workers suffering from disabling neck
      pain without any signs of physical abnormalities in the neck area. The TEA
      Personality Test (TPT), a self-report instrument designed to evaluate personality
      traits related to organizational behaviors, was used. Compared to the normative
      data, the study sample obtained high scores in the Depression, Anxiety and
      Emotional Instability scales, thus suggesting a personality profile primarily
      characterized by high neuroticism-related scores. Controlling for age, gender,
      and any rehabilitation undergone, we found a positive relationship between
      Depression and the duration of sick leave (in weeks). Moreover, lower scores on
      the TPT personality trait Dynamism and activeness were associated with higher
      likelihood of sick leave recurrence. These findings highlight the need for
      further research into the role played by personality at the onset and in the
      maintenance of nonorganic neck pain. Furthermore, they suggest that a
      complementary psychological approach may be useful to nonorganic neck pain
      management.

PMID- 23156932
TI  - Autonomy support, basic psychological needs and well-being in Mexican athletes.
AB  - Based on Basic Needs Theory, one of the mini-theories of Self-determination
      Theory (Ryan & Deci, 2002), the present study had two objectives: (a) to test a
      model in the Mexican sport context based on the following sequence: perceived
      coach autonomy support, basic psychological needs satisfaction, and psychological
      well-being, and b) to analyze the mediational effect of the satisfaction of
      perceived coach autonomy support on indicators of psychological well-being
      (satisfaction with life and subjective vitality). Six hundred and sixty-nine
      young Mexican athletes (Boys = 339; Girls = 330; M(age) = 13.95) filled out a
      questionnaire assessing the study variables. Structural equations analyses
      revealed that perceived coach autonomy support predicted satisfaction of the
      basic psychological needs for autonomy, competence, and relatedness. Furthermore,
      basic need satisfaction predicted subjective vitality and satisfaction with life.
      Autonomy, competence and relatedness partially mediated the path from perceived
      coach autonomy support to psychological well-being in young Mexican athletes.

PMID- 23156933
TI  - Well-being and prejudice toward obese people in women at risk to develop eating
      disorders.
AB  - The literature has found that eating disorders (ED) patients usually have a
      depression and anxiety diagnosis. However, not many investigations have studied
      the relationship between ED and well-being. One of the main problems of patients
      with ED is their body image. These individuals usually see themselves too big but
      there are not many investigations that focus on how these patients see people
      with real weight problems. For this reason in this study it is analyzed how women
      in risk to develop ED see obese people. 456 female students were selected. It was
      found that women with high scores in the different subscales of the Eating
      Attitudes Test 26 (EAT-26; dieting, bulimia and oral control) had lower well
      being (both subjective and psychological) and worse attitudes toward obese people
      (measured with Antifat Attitudes Test, AFA, Beliefs About Obese People Scale,
      BAOP, and Attitudes Toward Obese People Scale, ATOP) compared with women with low
      scores in the EAT-26.

PMID- 23156934
TI  - Quality of life and emotional distress among HIV-positive women during transition
      to motherhood.
AB  - The purpose of this preliminary study was to describe the quality of life (QOL)
      and emotional distress during pregnancy and early postpartum, and to examine the
      ability of psychopathological symptoms to predict QOL at early postpartum. A
      sample of 75 pregnant women (31 HIV-positive and 44 HIV-negative) was assessed
      during the second trimester of pregnancy and two to four days postpartum. QOL was
      assessed with the WHOQOL-Bref. The emotional distress was assessed with the Brief
      Symptom Inventory, and with the Emotional Assessment Scale. Seropositive women
      reported increased negative emotional reactivity and lower scores in social
      relationships and overall QOL during pregnancy than HIV-negative women. Both HIV
      positive and HIV-negative women reported better QOL after the birth of their
      child, when compared with the pregnancy period. Among HIV-positive women, lower
      anxiety and depressive symptoms during pregnancy were, respectively, significant
      predictors of better psychological QOL and overall QOL at early postpartum. Less
      intense somatic symptoms predicted better physical QOL. Longitudinal assessment
      of QOL and emotional status may provide potentially useful information for
      tailoring psychological interventions in the maternity care of HIV-infected
      women, during their transition to motherhood.

PMID- 23156935
TI  - Portuguese adolescents: the importance of parents and peer groups in positive
      health.
AB  - The purpose of this study is to examine the influence of peer groups and parents
      on adolescents' health. It was examined how communication relationships with peer
      groups and parents affect youngsters life satisfaction, sadness, irritability,
      being nervous, fear and troubles in falling asleep. The sample was comprised of
      individuals that participated in the study in continental Portugal, integrating
      the European study HBSC - Health Behavior in School - aged Children. The study
      was made during January 2006 and included a total of 4,877 students attending the
      6th, 8th and 10th grades from Portuguese public schools, with an average age of
      14 years of age. The instrument used was the HBSC questionnaire. The results
      showed that adolescents' health is influenced by their relationship with their
      parents and peers. When the communication with both is easy, youngsters are more
      satisfied with life and have less health negative symptoms. When compared with
      peers, parents influence positively the adolescents' health.

PMID- 23156936
TI  - Professionals' criteria for detecting and reporting child sexual abuse.
AB  - Professionals who are likely to come into contact with children play an essential
      role in the protection of children, thus we aimed to study the criteria they use
      to identify and report child sexual abuse cases. Based on the Factorial Survey
      design, we presented 974 Spanish (90%) and Latin American professionals from six
      fields (Psychology, Social Services, Education, Health, Law and Security) with
      hypothetical situations of sexual interaction with minors (systematically varying
      the type of sexual act, the child's and the other person's sex and age, the use
      of coercion and the type of strategy employed to involve the child), in order to
      examine their perception of abuse and willingness to report. According to
      results, the factors or criteria that most impact assessments are age asymmetry
      and use of coercion. Specifically, professionals are significantly more likely to
      perceive abuse and intend to report it if the other person involved in the
      interaction is much older than the minor and/or uses a coercive strategy,
      especially force, drugs or blackmail. Another relevant criterion is the type of
      sexual act, since acts involving intercourse, digital penetration or oral sex are
      significantly more likely to be deemed as abuse and reported.

PMID- 23156937
TI  - Prediction of PTSD in police officers after six months--a prospective study.
AB  - The aim of this prospective study was to explore the predictors for the
      development of PTSD in police officers six months after encountering situations
      of a potentially traumatic nature. Fifty-nine police officers were studied
      immediately after the event (T1) and six months later (T2). At T2 PTSD was
      assessed using the Structured Clinical Interview for DSM-IV (SCID-I). PTSD was
      predicted by intrusions (Impact of Event Scale-Revised; IES-R), the impairment
      scale (is), global assessment of functioning scale (GAF), gender, age and sense
      of coherence scale (SOC). The diagnosis of an acute stress disorder (ASD) at T1
      had a high specificity for identifying PTSD at T2. The strongest predictor for
      the development of PTSD was found to be the factor intrusions. Contrary to our
      expectations, age was not a significant predictive factor for PTSD. Thus, acute
      stress disorder (ASD) and a high degree of intrusions experienced immediately
      after a traumatic incident helped to identify early police officers at risk of
      developing chronic PTSD.

PMID- 23156938
TI  - What predicts retention on an in-prison drug treatment program?
AB  - The effectiveness of treatments for substance use disorders is strongly related
      to retention, since early dropout from treatment is associated with greater
      likelihood of relapse. The purpose of this prospective, ex post facto study is to
      analyze the effect of individual variables on retention in a treatment program
      carried out in a prison drug-free unit. The Addiction Severity Index, motivation
      and personality profile of fifty inmates were assessed on entry to the prison.
      Inmates were monitored for a year to identify length of stay. RESULTS: Motivation
      variables at intake play a vital role in the prediction of retention in a prison
      drug-free unit; scores on the Aggressive-Sadistic and Narcissistic scales are
      also strong predictors of treatment retention.

PMID- 23156939
TI  - Impact of acceptance-based nursing intervention on postsurgical recovery:
      preliminary findings.
AB  - Research has shown that teaching individuals to experience pain and anxiety as
      inevitable products of the actions they freely and responsibly undertake yields
      healthier reactions to suffering. This preliminary study assesses whether a brief
      acceptance-based psychological intervention along with the usual presurgical
      protocol for a laparoscopic cholecystectomy will produce healthier reactions to
      postsurgical pain, and will reduce anxiety, duration of postsurgical
      hospitalization, and demand of analgesics. After admission, screening, and
      consent procedures, we assessed pain and anxiety. Patients in the experimental
      condition (n = 6) then received a brief acceptance-based nursing intervention
      addressing the individual meaning of surgery, and including a metaphor and
      defusion practice, along with routine care. Patients in the control condition (n
      = 7) received routine care only. Twenty-four hr following the intervention,
      surgery took place. Pain, anxiety, and patients' demand for analgesics were
      assessed 24 hr or 48 hr after surgery. All six experimental patients, as compared
      to three of seven control patients, demanded fewer analgesics and left the
      hospital within 24 hr or 48 hr from surgery even in the presence of frequent
      and/or intense pain. Anxiety slightly decreased in the experimental patients. The
      brief acceptance-based intervention was effective in improving postsurgical
      recovery. These preliminary findings support the potential of this type of
      intervention as a cost-effective strategy to be implemented in the sanitary
      context.

PMID- 23156940
TI  - Effectiveness of rhythmic movement therapy for disordered eating behaviors and
      obesity.
AB  - The aims of the present study were: a) to examine associations between pre
      treatment BMI, body dissatisfaction, perfectionism, alexithymia, and restraint,
      emotional and external eating behaviour in obese patients; b) to analyze the
      impact of the pre-treatment measures in psychological variables on the outcome of
      cognitive-behavioral therapy (CBT) program; c) to test the effectiveness of
      rhythmic movement therapy (RMT) in the treatment of disordered eating behaviors
      and obesity with the CBT non-responders. At the first stage of treatment a total
      of 104 patients (32 males and 72 females, mean age was 37.6 +/- 6.7 years) self
      referred or referred by professionals to CBT weight management program were
      selected at random. At the second stage 58 obese CBT-non-responders were randomly
      divided among the continuing CBT individual treatment group and RMT group.
      Control group was included. Results revealed that: a) significant associations
      existed between pre-treatment BMI, external eating and two dimensions of
      perfectionism, as well as between emotional and external eating and all
      dimensions of perfectionism, alexithymia and body image dissatisfaction; b) pre
      treatment means of psychological variables significantly impacted the CBT program
      outcome; c). the efficacy of RMT approach for weight reduction as well as for the
      improvement of psychological status for CBT-non-responders was confirmed.

PMID- 23156941
TI  - Effectiveness of cognitive-behavioral treatment for major depressive disorder in
      a university psychology clinic.
AB  - Major Depressive Disorder (MDD) is the most prevalent mental disorder in our
      environment, and one of the main causes of disability. While several empirically
      supported treatments (ESTs) for MDD exist, some doubts have been cast on the
      applicability--in time, components, and effectiveness--of these ESTs in routine
      clinical practice. A few attempts have been made to contrast the effectiveness of
      ESTs, but usually the precise components of the treatment developed are not
      considered in detail. The purpose of this study is to analyze the components of
      an EST-based treatment on a sample of 69 MDD cases from a University Psychology
      Clinic, and to benchmark them against the results of published efficacy studies
      on ESTs (behavioral activation, cognitive therapy, interpersonal therapy).
      Results show that treatments delivered at this clinical facility are similar in
      components, length, and effectiveness (in effect size, completers and improved
      ratio) to the benchmarked studies. Cognitive restructuring is the most frequent
      component of the delivered treatments. Therapy results show a 3.12 effect size,
      and a 55.1% improved ratio over initial sample, an 80% of completers. Results and
      limitations of the current study, especially those related to sample and center
      characteristics, are discussed.

PMID- 23156942
TI  - Validation of Children's Depression Scale in the Basque-speaking population.
AB  - The aim of this study was to validate the Basque version of the CDS (Children's
      Depression Scale, Lang & Tisher, 1978), one of the most widely used
      questionnaires for the assessment of childhood depression, which has already been
      proved to be a valid and reliable tool in different cultures. The questionnaire
      was administered to a community sample of 886 participants (432 males and 454
      females) aged between 8 and 16. A two-factor solution was obtained (Depressive
      dimension and Positive Dimension), which accounted for 29.86 % of the variance.
      Reliability with regard to internal consistency level and long-term stability was
      good (alpha = .95 and .79; and R = .73 and .59 for Depressive and Positive
      dimensions, respectively). Analysis of Differential Item Functioning with respect
      to age and gender showed that 91% and 88% of the items, respectively, did not
      present DIF. External validity evidence for the questionnaire was also obtained.
      We consider that the present work offers researchers and professionals interested
      in this area of study a valid and reliable tool for assessing depressive symptoms
      in Basque-speaking children and adolescents.

PMID- 23156943
TI  - When I don't like myself: Portuguese version of the Internalized Shame Scale.
AB  - In the past two decades, there has been a growing theoretical and empirical
      interest on the role of shame, namely internal shame, on the conceptualization of
      human functioning and several interpersonal and emotional problems. The current
      study explores the psychometric properties of the Portuguese version of the
      Internalized Shame Scale (ISS), a self-report measure which assesses trait shame,
      composed by an Internal Shame subscale, measuring internalized shame, and a Self
      Esteem subscale. The factor structure, internal consistency, test-retest
      reliability and convergent and discriminant validity for both subscales, are
      presented, in a sample of 385 college students. The Principal Components Analyses
      reveal that both Internal Shame and Self-Esteem subscales present a one
      dimensional structure which explains, respectively, 48.54% and 57.7% of the
      variance. The subscales present high internal consistency, with high Cronbach'
      alphas (.95 and .85) and moderate to high item-total correlations. The two
      subscales present an excellent temporal stability. Convergent and discriminant
      validity of the subscales was corroborated through the moderate correlations with
      a measure of shame and of social comparison, and through the low and moderate
      correlations with the subscales depression, anxiety, and stress. The Portuguese
      version of the ISS is a valid and reliable instrument to measure internalized
      shame.

PMID- 23156944
TI  - The Memory Failures of Everyday (MFE) test: normative data in adults.
AB  - One approach to the study of everyday memory failures is to use multiple-item
      questionnaires. The Memory Failures of Everyday (MFE) test is one of the most
      frequently used in Spain. Our objective is to provide normative data from the MFE
      in a sample of healthy, Spanish, adult participants for use in clinical practice.
      The sample consists of 647 employees at a large company ranging in age from 19-64
      years-old. Everyday memory failures were evaluated by means of the MFE with the
      following response format: 0-2 (0 = never or rarely; 1 = occasionally, sometimes;
      2 = frequently, often). RESULTS: Mean MFE = 15.25 (SD = 7.50), range 0-40.
      Correlation with age: .133 (p = .001); and with years of education: - .059
      (n.s.). A constant increase in MFE was not observed across age groups (F = 4, 59;
      p = .003, eta2 = .02), but differences were revealed between the 19-29 and 40-49
      age groups; no differences were observed between the remaining age groups. Only
      slight differences between men and women occurred, the women's mean being
      slightly higher than the men's, but the confidence intervals overlapped (F = 5,
      71; p = .017, eta2 = .01). These results indicate that age, years of education,
      and sex had no significant effects. In light of the above, the sample was viewed
      as a whole when computing the percentiles reported here.

PMID- 23156945
TI  - Measuring the desire for control: a Spanish version of Burger and Cooper's Scale.
AB  - The following study will present findings on the validity of the adaptation of
      the Burger and Cooper's Desirability of Control Scale into Spanish. Two samples
      are present: the first involving 1,999 people to study their psychometric
      properties. In the second sample, 111 people were included to estimate
      test/retest reliability. Cultural adaptation was performed using the translation
      & back-translation method. Item analysis, internal consistency and test/retest
      reliability were assessed, then evidence of the validity of the internal
      structure was determined by using exploratory and confirmatory factor analysis.
      Subject recruitment was performed to gather the 1,999 subjects stratified by age,
      gender quotas as designed in the sampling plan. Of the subjects, 51% were female,
      average age of 45 years old (SD = 17.5). All items from the original scale were
      understood correctly, while five items presented ceiling effect. Cronbach's alpha
      = .736 and a test-retest correlation r = .713 were obtained. The factor structure
      indicated the presence of four dimensions: forecast, autonomy, power and
      influence and reactance which were reassured in the confirmatory analysis
      (chi2/df = 4.805, CFI = .932, TLI = .954, RMSEA = .062). The basic dimensions of
      the scale have shown to be stable and well-defined, though not perfect. The
      scope, possible applications of the scale and further research are later proposed
      and discussed.

PMID- 23156946
TI  - School Motivation Questionnaire for the Portuguese population: structure and
      psychometric studies.
AB  - It is presented the structure and psychometric studies of the "School Motivation
      Questionnaire". The SMQ is a self-report questionnaire with 101 items, organized
      in sixteen scales that measure the students' goal orientations, the perceived
      classroom goal structures, the perceived teacher's autonomy support and the use
      of learning strategies. Twelve scales are adapted from the "Learning Climate
      Questionnaire", "Perceptions of Instrumentality" and "Cuestionario a
      Estudiantes". Four scales and five additional items are created new. The
      psychometric studies rely on a convenience sample consisting of 9th and 12th
      grade students (N = 485) of Portuguese schools. The factorial and construct
      validity, verified through several exploratory factorial analyses to the data,
      presents a final solution of six factors, labelled Strategies (F1), Teacher
      Extrinsic Goals (F2), Student Extrinsic Goals, Externally Regulated (F3) Teacher
      Intrinsic Goals (F4), Student Extrinsic Goals, Internally Regulated (F5), and
      Student Intrinsic Goals (F6). The six-factor solution explains a significant
      variance of the scale results (53.95%). Good coefficients of internal consistency
      are obtained for all factors, never below (.858; F6). In sum there is strong
      evidence to support the multi-dimensionality of SMQ, upholding that the data
      obtained is exploratory and applies for future validation studies.

PMID- 23156947
TI  - Development and validation of a measuring instrument for burnout syndrome in
      teachers.
AB  - This paper is part of a research done on Burnout Syndrome, and its objective is
      to develop and validate an instrument for measuring the syndrome in Secondary
      School teachers, taking as a principal starting point Maslach, Schaufeli, and
      Leiter's theory (2001). After developing and testing the instrument on a sample
      of 794 teachers in the Community of Madrid (Spain), we analyzed the reliability,
      content and construct validity (the latter by means of Structural Equations
      Models implemented with Software AMOS 7.0). The reliability analysis (alpha =
      .911 for the total instrument; .849, .899 and .674 for the dimensions of
      Exhaustion, Reduced Personal Accomplishment and Depersonalization respectively)
      and the Confirmatory Factorial Analysis (CMIN/DF = 4.163, CFI = .904, RMSEA =
      .60, PRATIO = .874) showed highly satisfactory results. The discrimination
      coefficient scores for items in the final instrument ranged between .22 and .74.
      Thus, the instrument presented combines the necessary technical characteristics
      for it to be considered a valid and reliable tool for measuring the syndrome.

PMID- 23156948
TI  - Measuring autonomy support in university students: the Spanish version of the
      Learning Climate Questionnaire.
AB  - The goals of this research were to translate and analyze the psychometric
      properties of the Learning Climate Questionnaire (LCQ) and to develop a short
      form. The LCQ is a 15-item self-report measure that assesses autonomy support in
      educational settings. A total of 422 students (60 men and 362 women) took part in
      this study. Results showed evidence of construct validity and adequate
      reliability for the LCQ. The short form consists of five items that showed sound
      psychometric properties. Results of Pearson correlation and Gower index showed
      high agreement between the long and short forms. In conclusion, both forms can be
      considered as preliminary versions of the original questionnaire to assess
      autonomy support in educational settings.

PMID- 23156949
TI  - School Social Behavior Scales: an adaptation study of the Portuguese version of
      the social competence scale from SSBS-2.
AB  - This study analyses the psychometric proprieties of a Portuguese version of the
      social competence scale from the School Social Behavior Scales (SSBS-2, Merrell,
      2002). It is a rating instrument of children and adolescents behavior, to be used
      by teachers and other school personnel. This scale includes 3 subscales: self
      management/compliance, peer relations and academic behavior. In our first sample,
      175 teachers rated 344 students from grade 1 through 12. On the second sample 13
      teachers rated 251 3rd and 4th grades students. The results from the Portuguese
      adaptation support the multidimensional structure of the social competence scale
      from the SSBS-2, although an alternative model demonstrated a better fit to the
      data than the model originally proposed by the author. The scale showed good
      internal consistency and good intercorrelations between subscales, as well as
      between subscales and the total scale. The final model was well replicated in the
      second sample. These results encourage us to pursue the SSBS-2 Portuguese
      adaptation, in order to provide a useful and validated instrument for the
      assessment of social competence and for educational interventions.

PMID- 23156950
TI  - Spanish version of the Time Management Behavior Questionnaire for university
      students.
AB  - The main objective of the study is to analyze the psychometric properties and
      predictive capacity on academic performance in university contexts of a Spanish
      adaptation of the Time Management Behavior Questionnaire. The scale was applied
      to 462 students newly admitted at the Universitat de Valencia in the 2006-2007
      school year. The analyses performed made it possible to reproduce the factorial
      structure of the original version of the questionnaire with slight modifications
      in the ascription of various items. The underlying factorial structure includes
      four interrelated dimensions (Establishing objectives and priorities, Time
      management tools, Perception of time control and Preference for disorganization),
      which present satisfactory levels of reliability and an adequate convergent
      validity with the Time management subscale of the Motivated Strategies for
      Learning Questionnaire. The scores on the dimensions of time management show
      significant levels of association with academic performance in the first year of
      university studies, especially highlighting the predictive capacity of the
      subscale dealing with the Establishment of objectives and priorities. These
      results show the reliability and validity of this adaptation of the scale for
      evaluating how the students manage their academic time, and predicting their
      performance in the year they initiate the degree program, thus aiding in the
      development of intervention proposals directed towards improving these skills.

PMID- 23156951
TI  - Spanish version of the Positive Expectancies for Drinking and Driving for Youth.
AB  - In most developed countries, motor vehicle accidents are a leading cause of death
      among young people, and a large proportion of motor vehicle accidents are alcohol
      related. In Spain there are no currently available instruments for assessing
      positive expectancies related to drinking and driving behavior. Attempting to
      modify these expectancies may be an effective prevention approach, so there is a
      need for a valid and reliable scale to measure the construct. The aims of the
      present study were to translate, culturally adapt, and examine the psychometric
      properties of a Spanish-language version of the Positive Expectancies for
      Drinking and Driving for Youth (PEDD-Y) in a sample of Spanish young adults. A
      total of 352 college students with drivers licenses were recruited at a
      university in southeast Spain. We examined the factor structure, psychometric
      properties (reliability and validity) and temporal stability of the Spanish
      version of the PEDD-Y among Spanish young adult drivers. Findings indicated that
      the Spanish version of the PEDD-Y demonstrated satisfactory psychometric
      properties and was shown to significantly predict lifetime prevalence and future
      intentions to drink and drive as well as riding with a drunk driver. The
      Convenience factor performed with the most consistent reliability and predictive
      validity. Limitations and future research questions are discussed.

PMID- 23156952
TI  - A revised Thai Multi-Dimensional Scale of Perceived Social Support.
AB  - In order to ensure the construct validity of the three-factor model of the Multi
      dimensional Scale of Perceived Social Support (MSPSS), and based on the
      assumption that it helps users differentiate between sources of social support,
      in this study a revised version was created and tested. The aim was to compare
      the level of model fit of the original version of the MSPSS against the revised
      version--which contains a minor change from the original. The study was conducted
      on 486 medical students who completed the original and revised versions of the
      MSPSS, as well as the Rosenberg Self-Esteem Scale (Rosenberg, 1965) and Beck
      Depression Inventory II (Beck, Steer, & Brown, 1996). Confirmatory factor
      analysis was performed to compare the results, showing that the revised version
      of MSPSS demonstrated a good internal consistency--with a Cronbach's alpha of .92
      for the MSPSS questionnaire, and a significant correlation with the other scales,
      as predicted. The revised version provided better internal consistency,
      increasing the Cronbach's alpha for the Significant Others sub-scale from 0.86 to
      0.92. Confirmatory factor analysis revealed an acceptable model fit: chi2 128.11,
      df 51, p < .001; TLI 0.94; CFI 0.95; GFI 0.90; PNFI 0.71; AGFI 0.85; RMSEA 0.093
      (0.073-0.113) and SRMR 0.042, which is better than the original version. The
      tendency of the new version was to display a better level of fit with a larger
      sample size. The limitations of the study are discussed, as well as
      recommendations for further study.

PMID- 23156953
TI  - A method to analyse measurement invariance under uncertainty in between-subjects
      design.
AB  - In this research we have introduced a new test (H-test) for analyzing scale
      invariance in between group designs, and considering uncertainty in individual
      responses, in order to study the adequacy of disparate rating and visual scales
      for measuring abstract concepts. The H-test is easy to compute and, as a
      nonparametric test, does not require any a priori distribution of the data nor
      conditions on the variances of the distributions to be tested. We apply this test
      to measure perceived service quality of consumers of a sports services. Results
      show that, without considering uncertainty, the 1-7 scale is invariant, in line
      with the related works regarding this topic. However, de 1-5 scale and the 1-7
      scale are invariant when adding uncertainty to the analysis. Therefore, adding
      uncertainty importantly change the conclusions regarding invariance analysis.
      Both types of visual scales are not invariant in the uncertainty scenario.
      Implications for the use of rating scales are discussed.

PMID- 23156954
TI  - Behavioral regulation assessment in exercise: exploring an autonomous and
      controlled motivation index.
AB  - The main purpose of this study was to examine the psychometric properties of the
      Portuguese version of the Behavioral Regulation in Exercise Questionnaire (BREQ
      2) and to test the hypothesis that the different types of behavioral regulation
      can be combined on a single factor to assess autonomous and controlled
      motivation. Data were collected from 550 members of private fitness centres who
      ranged in age from 14 to 69 years. The analysis supported an 18-item, 5-factor
      model after excluding one item (S-B chi2 = 221.7, df = 125, p = .000, S-B chi2/df
      = 1.77; SRMR = .06; NNFI = .90; CFI = .92; RMSEA = .04, 90% CI = .03-.05).
      However, the analysis also revealed a lack of internal consistency. The results
      of a hierarchical model based on 2 second-order factors that reflected controlled
      motivation (external and introjected regulation) and autonomous motivation
      (identified and intrinsic regulation) provided an acceptable fit to the data (S-B
      chi2 = 172.6, df = 74, p = .000, S-B chi2/df = 2.33; SRMR = .07; NNFI = .90; CFI
      = .92; RMSEA = .05, 90% CI = .04-.06), with reliability coefficients of .75 for
      controlled motivation and .76 for autonomous motivation. The study findings
      indicated that when item 17 was excluded, the Portuguese BREQ-2 was an
      appropriate measure of the controlled and autonomous motivation in exercise.

PMID- 23156955
TI  - Adaptation of the Athlete Burnout Questionnaire in a Spanish sample of athletes.
AB  - In this paper, we offer a general version of the Spanish adaptation of Athlete
      Burnout Questionnaire (ABQ) designed to measure the syndrome of burnout in
      athletes of different sports. In previous works, the Spanish version of ABQ was
      administered to different samples of soccer players. Its psychometric properties
      were appropriate and similar to the findings in original ABQ. The purpose of this
      study was to examine the generalization to others sports of the Spanish
      adaptation. We started from this adaptation, but we included three alternative
      statements (one for each dimension of the questionnaire), and we replaced the
      word "soccer" with the word "sport". An 18-item version was administered to a
      sample of 487 athletes aged 13 and 29 years old. Confirmatory factor analyses
      replicated the factor structure, but two items modification were necessary in
      order to obtain a good overall fit of the model. The internal consistency and
      test-retest reliability of the questionnaire were satisfactory.

PMID- 23156956
TI  - Tornados and terrorists.

PMID- 23156957
TI  - The burden of disaster: Part I. Challenges and opportunities within a child's
      social ecology.
AB  - Child development and adaptation are best understood as biological and
      psychological individual processes occurring within the context of
      interconnecting groups, systems, and communities which, along with family,
      constitute the child's social ecology. This first of two articles describes the
      challenges and opportunities within a child's social ecology consisting of Micro
      , Meso-, Exo-, and Macrosystems. The parent-child relationship, the most salient
      Microsystem influence in children's lives, plays an influential role in
      children's reactions to and recovery from disasters. Children, parents, and other
      adults participate in Mesosystem activities at schools and faith-based
      organizations. The Exosystem--including workplaces, social agencies,
      neighborhood, and mass media--directly affects important adults in children's
      lives. The Macrosystem affects disaster response and recovery indirectly through
      intangible cultural, social, economic, and political structures and processes.
      Children's responses to adversity occur in the context of these dynamically
      interconnected and interdependent nested environments, all of which endure the
      burden of disaster Increased understanding of the influences of and the
      relationships between key components contributes to recovery and rebuilding
      efforts, limiting disruption to the child and his or her social ecology A
      companion article (R. L. Pfefferbaum et al., in press) describes interventions
      across the child's social ecology.

PMID- 23156958
TI  - Church attendee help seeking priorities after Hurricane Katrina in Mississippi
      and Louisiana: a brief report.
AB  - After a disaster, survivors find themselves seeking many types of help from
      others in their communities. The purpose of this exploratory study was to assist
      in mental health service planning by determining the type and priority of support
      services sought by church attendees after Hurricane Katrina. Surveys were given
      to church attendees from two Mississippi coast and four New Orleans area churches
      that were directly affected by Hurricane Katrina participants were asked to
      review a list of 12 potential sources of help and were asked to rank the items
      chronologically from whom they had sought help first after Hurricane Katrina.
      Overall, participants sought out assistance from informal social networks such as
      family and friends first, followed by governmental and clergy support. This study
      also showed there may be differences in help-seeking behaviors between church
      attendees in more urban areas versus church attendees in more rural areas.
      Moreover, findings highlighted that very few church attendees seek out mental
      health services during the initial impact phase of a disaster. Since timely
      engagement with mental health services is important for resolving trauma,
      strategies that link professional mental health services with clergy and
      government resources following a disaster could improve the engagement with
      mental health professionals and improve mental health outcomes. Disaster mental
      health clinical implications and recommendations are offered for psychologists
      based on these findings.

PMID- 23156959
TI  - The influence of indirect collective trauma on first responders' alcohol use.
AB  - Previous research has suggested increased risk for negative outcomes such as
      increased alcohol use among first responders who are involved with the response
      to a community disaster; however it is not clear how indirect exposure to a
      critical incident impacts first responders. This work examined the impact of
      secondary or indirect trauma on changes in alcohol use among urban firefighters
      who were not directly involved in the response to a large scale community-level
      disaster. Firefighters enrolled in larger trial of health outcomes whose
      interview period coincided with the crash of a commercial airplane were the basis
      for the current report. Aggregate level data on changes in alcohol consumption
      for these firefighters were examined pre- and post-incident. There was a
      significant increase in alcohol use following the critical incident. This
      increase did not occur immediately; it was observed within several days and
      peaked about 8 days post-incident. Post-hoc analyses revealed that the increased
      alcohol consumption persisted for several months, finally returning to pre
      incident levels by 8 months post-incident. Indirect trauma effects, likely
      operationalized in part through the "brotherhood" of the firefighters, clearly
      placed firefighters at risk for negative outcomes following a disaster.
      Intervention/prevention efforts aimed at distress reduction among first
      responders should not solely focus on responders with direct involvement in a
      disaster.

PMID- 23156960
TI  - The effectiveness of cumulative stress debriefings with law enforcement
      personnel.
AB  - This article describes an intervention based on the Mitchel and Everly (1995)
      model of Critical Incident Stress Management, yet used to address the cumulative
      stress associated with being a police officer. This intervention occurred for
      eight weeks with thirty-eight police officers, while on duty. Half of this group
      met once a week as part of the treatment condition. There was no statistical
      difference between the control and treatment group. These officers viewed the
      intervention as helpful and reported that it should continue, which it did with
      one of the treatment groups. Implications for addressing the psychological needs
      of police officers and for future research are discussed.

PMID- 23156961
TI  - Behind the blue shadow: a theoretical perspective for detecting police suicide.
AB  - Police officers are at increased risk for suicide. Reluctance by this population
      to self-report suicidal thoughts requires detection on a different level. Based
      on existing theory, this paper discusses a possible alternative method for
      detecting suicidal tendencies among police officers: the suicide Implicit
      Association Test (IAT). The IAT measures the implicit strength of cognitive
      identification with death opposed to life. Previous work has demonstrated that a
      cognitive identification with death over life is associated with both suicide
      attempts and completions. The clinical application of implicit cognitions, along
      with other proven clinical measures, may be of value in detecting suicide
      ideation in police officers or other high suicide risk groups who are hesitant to
      explicitly report suicidal thoughts. More research is needed to help clarify the
      clinical usefulness of the IAT and its validity over time.

PMID- 23156962
TI  - Hostage (crisis) negotiation: the potential role of negotiator personality,
      decision-making style, coping style and emotional intelligence on negotiator
      success.
AB  - This article explores the potential role of hostage negotiator characteristics
      and the impact of psychological constructs on negotiator success. It explores the
      role of Personality, Decision-Making Style, Coping Style, Cognitive Coping Style
      and Emotion Regulation and Emotional Intelligence within high stress environments
      and occupations. The findings suggest that certain individual traits and
      characteristics may play a role in negotiator success, via the mediation of
      specific styles, which are conducive to effective crisis negotiation skills. It
      is proposed that these findings have application within the field of
      hostage/crisis negotiation in the format of guidance regarding the recruitment
      and selection of hostage negotiators and the identification of potential training
      needs within individual negotiators in order to maximize their efficacy within
      the field. In line with this, it is argued that a psychometric tool that assesses
      these constructs is developed in order to aid the process of hostage negotiation
      selection.

PMID- 23156963
TI  - Orofacial myofunctional therapy: why now?

PMID- 23156964
TI  - Technology is here to stay.

PMID- 23156965
TI  - Masseter and temporalis excursive hyperactivity decreased by measured anterior
      guidance development.
AB  - The purpose of this study was to determine if a statistically significant
      reduction in muscle activity (p<0.05) occurs when prolonged disclusion time (>0.4
      sec/excursion) is shortened to <0.4 sec/excursion with the Immediate Complete
      Anterior Guidance Development (ICAGD) enameloplasty. Forty-five symptomatic,
      fully informed subjects (29 female, 16 male) had their right and left disclusion
      times recorded with T-Scan III, while simultaneously, the bilateral masseter and
      anterior temporalis muscle activity was recorded electromyographically with
      BioEMG III (n=180 muscles). This recording was done twice, once pretreatment and
      again posttreatment (same day) after undergoing the ICAGD enameloplasty on the
      same day without changing electrodes. The Student's paired t-test was utilized to
      detect any significant change in the muscle activity levels between the pre- and
      posttreatment lateral excursive muscle contractions. Highly significant
      reductions were found in all four muscles' activities after shortening the
      pretreatment prolonged disclusion time to less than 0.4 seconds (p<0.0014); after
      Bonferroni correction (p<0.006). When properly performed, such that the
      posttreatment disclusion time is <0.4 sec/excursion, the ICAGD enameloplasty
      predictably reduces excursive muscle activity levels in the bilateral anterior
      temporalis and masseter muscles. Excursive muscle hyperactivity can be a source
      of lactic acid accumulation, muscular ischemia, and chronic myalgic
      temporomandibular joint dysfunction (TMD) symptoms. The ICAGD enameloplasty
      significantly reduces excursive muscle contractions after completion of the first
      ICAGD treatment session.

PMID- 23156966
TI  - Assessment of the reliability and repeatability of landmarks using 3-D
      cephalometric software.
AB  - The aim of this study was to analyze the reliability and repeatability of
      identification landmarks using 3-D cephalometric software. Ten orthognathic
      patients were selected for this study and underwent the following protocol: 1.
      radiographic evaluation (CBCT technique); 2. stone casts; 3. photos; and 4. 3-D
      cephalometric evaluation. Twenty-one hard tissue landmarks and 14 cephalometric
      measurements were taken three times (T1, T2, and T3) on each patient, with an
      interval of one week by two experts in orthodontics (A, B). Standard deviation
      and Pearson's correlation coefficient were calculated to evaluate intra- and
      inter-observer repeatability. The results showed a strong correlation for both
      intra- and inter-observer Pearson's correlation coefficient (>0.7). The current
      preliminary study showed that the reliability and repeatability of the
      identification landmarks were very high if the 3-D cephalometric landmarks are
      defined correctly in the three planes of the space. Further evaluation is
      necessary to better define the 3-D cephalometric system.

PMID- 23156967
TI  - Low level laser therapy as an adjunctive technique in the management of
      temporomandibular disorders.
AB  - The purpose of this study was to assess the effect of low level laser therapy on
      subjects with intra-articular temporomandibular disorders (IA-TMD), and to
      quantify and compare severity of signs and symptoms before, during, and after the
      laser applications. The sample consisted of 45 subjects randomly divided into
      three groups (G) of 15 subjects each: G-I: 15 individuals with IA-TMD submitted
      to an energy dose of 52.5 J/cm2; G-II: dose of 105.0 J/cm2; and G-III: placebo
      group (0 J/cm2). In all groups, the applications were performed on condylar
      points on the masseter and anterior temporalis muscles. Two weekly sessions were
      held for five weeks, totaling 10 applications. The assessed variables were:
      mandibular movements and painful symptoms evoked by muscle palpation. These
      variables were measured before starting the study, then immediately after the
      first, fifth, and tenth laser application, and finally, 32 days after completing
      the applications. The results showed that there were statistically significant
      differences for G-I and G-II at the level of 1% between the doses, as well as
      between assessments. Therefore, it was concluded that the use of low level laser
      increased the mean mandibular range of motion and reduced painful symptoms in the
      groups that received effective treatment, which did not occur in the placebo
      group.

PMID- 23156968
TI  - Sequential analysis of head movement during mandibular open-close movements in
      TMD patients with disc displacement with reduction.
AB  - This study examined relationships between starting points of head and mandibular
      movements in 11 female control subjects and 10 TMD patients showing disc
      displacement with reduction during consecutive open-close movements, using a six
      degree-of-freedom measuring device. During the first mandibular opening cycle, in
      the TMD group, head movement was significantly preceded in relation to mandibular
      movement when compared with the control group, and major differences in onset
      were seen between maximum and minimal values at the beginning of mandibular
      movements. After the second cycle, significant differences in starting points
      were not evident. In TMD patients showing disc displacement with reduction, in
      the first cycle, at the commencement of opening movements, it is proposed that
      the head precedes the mandible in order to compensate for irregular condylar
      movements, and the degree of the condylar movement irregularity might affect the
      onset relation between the head and the mandible.

PMID- 23156969
TI  - Is low level laser effective for the treatment of orofacial pain?: A systematic
      review.
AB  - The aim of this study was to assess the effectiveness of low level laser therapy
      (LLLT) as a treatment for orofacial pain considering the methodology of the
      studies. PubMed (1983-2009) and one conference proceeding were searched. Studying
      quality was assessed using a validated instrument. A high-quality score was
      defined as high or low. Outcomes were defined as either positive (+), neutral
      (0), or negative (-). Thirty-three studies met inclusion criteria. The best
      evidence synthesis method was used to formulate outcome of LLLT for each type of
      control group. LLLT vs. placebo pooling revealed high-quality trials in three of
      eight positive studies. In LLLT vs. other active treatment pooling, two high
      quality studies out of nine neutral trials were found. Quality of the trial was
      not significantly associated with neutral results (p=0.05). Only limited evidence
      indicated that LLLT is more effective than placebo, sham laser, and other active
      treatments.

PMID- 23156970
TI  - Degenerative changes in rat condylar cartilage induced by non-matching occlusion
      created by scattered orthodontic teeth-moving.
AB  - The effect of occlusion on the temporomandibular joint (TMJ) is debated. By
      inserting rubber-bands that were replaced by self-curing resin one week later,
      the left maxillary and the right mandibular first-molars were moved and kept
      mesially in Sprague-Dawley (SD) rats in both experimental I (EXP-I) and II (EXP
      II) groups, aiming to establish a non-matching cusp-to-fossa occlusal relation.
      Four weeks later, the left maxillary and the right mandibular third-molars were
      moved and kept distally in the EXP-II group. Degenerative changes, typically as a
      cell-free area, were observed in TMJs of the EXP groups. Binary logistical
      analysis indicated that the odds ratio of EXP group, EXP-II vs. EXP-I, on the
      incidence of a cell-free area, was 2.8 (p=.036). Time point, gender, and side did
      not have such effects (p>0.05). The results indicate that the persistence of more
      scattered non-matching cusp-to-fossa occlusion is more harmful to the condylar
      cartilage in terms of the incidence of degenerative changes.

PMID- 23156971
TI  - The use of electrognathography in jaw movement research: a literature review.
AB  - The measurement of mandibular movements is a complex task that can be simplified
      through the use of electrognathography (EGN), an examination that can be applied
      as an auxiliary method for the diagnosis or follow-up of the evolution of
      specific therapeutics applied to the stomatognathic system. The aim of the
      present study was to review the literature pertaining to the use of EGN as a
      method for monitoring jaw movements in the research and treatments related to the
      stomathognathic system. A literature review was made by searching for articles in
      PubMED, MEDLINE (1997-2010), MEDLINE (1966-1996), LILACS, Ovid, BBO and SciELO
      databases. In this systematic review, 373 articles were found, of these, 23
      articles were selected. The study concluded that EGN can be used with advantages
      in varied clinical situations, although it is a technique still not widely
      applied.

PMID- 23156972
TI  - Low level laser therapy for the treatment of temporomandibular disorders: a
      systematic review of the literature.
AB  - The authors performed a review of the literature to evaluate the efficacy of low
      level laser therapy (LLLT) for the treatment of temporomandibular disorders
      (TMD). Selection criteria included: 1) human subjects, 2) articles written in
      English, and 3) randomized placebo-controlled trials. Evaluation was performed
      according to the CONSORT 2010 criteria. A total of 14 articles were included in
      the review. Studies varied considerably in terms of methodological design,
      particularly regarding the site of application of the laser beam, the number of
      applications performed, their duration, the laser beam features (wavelength,
      frequency, output, dosage), and outcome measures. The outcome of the trials was
      controversial and not particularly related to any features of the laser beam, to
      the number of laser applications, and their duration. Based on the results of
      this review no definitive conclusions can be drawn on the efficacy of LLLT for
      the treatment of TMD. Many methodological differences among the studies,
      especially regarding the number and duration of laser applications and
      characteristics of the laser beam (wavelength, frequency, output), do not allow
      for standardized guidelines for effective treatment with LLLT. The only
      indication seems to be that LLLT is probably more effective for the treatment of
      TMJ disorders, and less effective for the treatment of masticatory muscle
      disorders.

PMID- 23156973
TI  - Hematologic and plasma biochemical values of hyacinth macaws (Anodorhynchus
      hyacinthinus).
AB  - The hyacinth macaw (Anodorhyncus hyacinthinus), considered the largest psittacine
      bird species in the world, is an endangered species, with a remaining population
      of approximately 6500 birds in the wild. To establish hematologic and plasma
      biochemical reference ranges and to verify differences related to sex, samples
      from 29 hyacinth macaws (14 males, 15 females) were obtained from birds
      apprehended from illegal wildlife trade and subsequently housed at the Sorocaba
      Zoo, Brazil. No significant differences in hematologic or plasma biochemical
      values were found between females and males. Compared with published reference
      values, differences were found in mean concentrations of total red blood cell
      count, corpuscular volume, corpuscular hemoglobin level, total white blood cell
      count, aspartate aminotransferase level, creatine kinase concentration, alkaline
      phosphatase concentration, and phosphorus level. Baseline hematologic and plasma
      biochemical ranges were established, which may be useful as reference values for
      clinicians working with this endangered species in captivity or rehabilitation
      centers.

PMID- 23156974
TI  - Sedation and physiologic response to manual restraint after intranasal
      administration of midazolam in Hispaniolan Amazon parrots (Amazona ventralis).
AB  - Administration of intranasal midazolam (2 mg/kg) was evaluated for sedation and
      effects on cloacal temperature, respiratory rate, and heart rate in manually
      restrained Hispaniolan Amazon parrots (Amazona ventralis). Adult parrots (n=9)
      were administered either midazolam (2 mg/kg) or an equal volume of saline
      solution intranasally before a 15-minute manual restraint in a complete crossover
      study. Respiratory rate and sedation scores were recorded before and during
      capture and during and after 15 minutes of manual restraint. Heart rate and
      cloacal temperature were recorded during manual restraint. After restraint, the
      parrots received intranasal flumazenil (0.05 mg/kg) or an equal volume of saline
      solution, and the recovery time was recorded. In those birds that received
      midazolam, sedation was observed within 3 minutes of administration, and
      vocalization, flight, and defense responses were significantly reduced during
      capture. During manual restraint, the mean rate of cloacal temperature increase
      was significantly slower and remained significantly lower in birds that received
      midazolam compared with controls. Mean respiratory rates were significantly lower
      for up to 12 minutes in parrots that received midazolam compared with those
      receiving saline solution. Flumazenil antagonized the effects of midazolam within
      10 minutes. No overt clinical adverse effects to intranasal midazolam and
      flumazenil administration were observed. Further studies on the safety of
      intranasal midazolam and flumazenil in this species are warranted.

PMID- 23156975
TI  - Effects of ultracentrifugation on plasma biochemical values of prefledged wild
      peregrine falcons (Falco peregrinus) in northeastern Illinois.
AB  - Centrifugation is performed on whole blood samples to obtain serum or plasma for
      biochemical analysis. Although blood samples centrifuged in a microhematocrit
      tube may maximize recovery of plasma from small-volume samples, plasma
      biochemical values from such samples have been implicated as causing erroneous
      results. To compare blood biochemical values obtained by microhematocrit
      centrifugation and centrifugation with a commercial tilt-rotor machine, blood
      samples were collected from peregrine falcon (Falco peregrinus) eyases aged 32-40
      days (n=51). The samples were separated into 2 equal aliquots with 1 aliquot
      centrifuged in a tilt-rotor machine and the other aliquot ultracentrifuged in
      microhematocrit tubes. Separated plasma from both processes was sent to a
      commercial veterinary reference laboratory for routine clinical biochemical
      analysis. No significant differences were found in the biochemical results of the
      paired samples by the 2 centrifugation methods. These results show that the
      centrifugation method has no effect on the plasma quality for biochemical
      analysis in young peregrine falcons.

PMID- 23156976
TI  - The detection of avian bornavirus within psittacine eggs.
AB  - Avian bornavirus (ABV) is a known cause of proventricular dilatation disease in
      parrots and encephalitis in waterfowl and is a significant cause of both
      morbidity and mortality in captive birds. Transmission is thought to occur
      primarily by the fecal-oral route. In an aviary setting, controlling the disease
      involves a thorough understanding of the complete transmission cycle, including
      determining whether vertical transmission occurs. In this study, vertical
      transmission of ABV was evaluated by using 61 eggs obtained from birds in 2
      aviaries where proventricular dilatation disease was prevalent, and the presence
      of ABV had been confirmed by fecal reverse transcription-polymerase chain
      reaction by using a primer set designed to detect ABV M protein. The contents of
      these eggs were then tested for the presence of ABV RNA. Of the eggs tested, 10
      were determined to contain ABV RNA. These eggs ranged from apparently nonviable
      to those that contained developing embryos. ABV was detected in the brain tissue
      of 2 embryos. It remains to be proven that infected chicks can hatch from these
      eggs to complete the vertical transmission cycle; however, these findings suggest
      that vertical transmission of ABV may occur.

PMID- 23156977
TI  - Nutritional levels of diets fed to captive Amazon parrots: does mixing seed,
      produce, and pellets provide a healthy diet?
AB  - Poor nutrition is a serious problem in captive psittacine birds. Seed-based diets
      are known to contain excess fat, low calcium:phosphorus ratios, and other
      nutrient deficiencies, whereas many consider nutritionally superior, formulated
      diets to be monotonous. As a result, many bird owners feed a mixture of seed,
      produce, and formulated diet. However, the nutritional contents of such mixed
      diets have rarely been evaluated. In this study, we describe the nutrient
      contents of diets consumed by 7 adult (>6 years old), captive Amazon parrots
      offered produce (50% fresh weight), formulated diet (25%), and seed (25%). Diets
      consumed were deficient in calcium, sodium, and iron and contained more than the
      recommended amount of fat. In addition, the birds chose foods that exacerbated
      these imbalances. Birds offered low-seed diets (60% pellet, 22% produce, 18%
      seed, wet weight) consumed diets with more fat than recommended but acceptable
      levels of calcium and all other nutrients measured, as well as acceptable
      calcium:phosphorus ratios. This suggests that small quantities of seeds may not
      result in nutritionally imbalanced diets. Birds fed 75% formulated diet and 25%
      produce consumed diets within the recommendations for nearly all measured
      nutrients, demonstrating that owners of psittacine birds should be encouraged to
      supplement manufactured diets with low energy-density, fresh produce items to
      provide stimulation and foraging opportunities without fear of causing major
      nutritional imbalances.

PMID- 23156978
TI  - Pharmacokinetics of nebulized terbinafine in Hispaniolan Amazon parrots (Amazona
      ventralis).
AB  - Aspergillosis is one of the most difficult diseases to treat successfully in
      avian species. Terbinafine hydrochloride offers numerous potential benefits over
      traditionally used antifungals for treatment of this disease. Adding nebulized
      antifungals to treatment strategies is thought to improve clinical outcomes in
      lung diseases. To determine plasma concentrations of terbinafine after
      nebulization, 6 adult Hispaniolan Amazon parrots were randomly divided into 2
      groups of 3. Each bird was nebulized for 15 minutes with 1 of 2 terbinafine
      solutions, one made with a crushed tablet and the second with raw drug powder.
      Blood samples were collected at baseline and at multiple time points up to 720
      minutes after completing nebulization. Plasma and nebulization solutions were
      analyzed by high-performance liquid chromatography. The terbinafine concentration
      of the solution made with a crushed tablet (0.87 +/- 0.05 mg/mL) was
      significantly lower than was that made with raw powder (1.02 +/- 0.09 mg/mL).
      Plasma concentrations of terbinafine did not differ significantly between birds
      in the 2 groups. Plasma terbinafine concentrations in birds were maintained above
      in vitro minimum inhibitory concentrations for approximately 1 hour in birds
      nebulized with the crushed tablet solution and 4 hours in birds nebulized with
      the raw powder solution. Higher concentrations of solution, longer nebulization
      periods, or more frequent administration are likely needed to reach therapeutic
      plasma concentrations of terbinafine for clinically relevant periods in
      Hispaniolan Amazon parrots.

PMID- 23156979
TI  - Implantation of a titanium partial limb prosthesis in a white-naped crane (Grus
      vipio).
AB  - A female white-naped crane (Grus vipio) was presented with an open, oblique
      fracture of the distal right tarsometatarsus and concomitant vascular and nerve
      damage. Conventional fracture fixation repairs failed, which led to implantation
      of a custom titanium limb prosthesis. After subsequent revisions with 2 different
      prosthetic devices, limb function was ultimately restored but a later yolk
      embolism caused a circulatory compromise in the opposite leg, which necessitated
      euthanasia. Histopathologic results revealed limited ingrowth of bone into the
      porous coated implant, which indicated that a limb prosthesis may provide salvage
      for long-legged, heavy-bodied birds with fractures of the tarsometatarsus.

PMID- 23156980
TI  - Ingluviotomy tube placement for lead-induced crop stasis in the California condor
      (Gymnogyps californianus).
AB  - Six free-flying California condors (Gymnogyps californianus) were diagnosed with
      acute lead toxicosis that caused crop distension and stasis. Between January 2006
      and January 2007, the birds were referred to the Phoenix Zoo in Arizona for
      emergency treatment. In 5 birds, an ingluviotomy was performed to place a feeding
      tube from the crop to the proventriculus, which allowed a temporary bypass of the
      dysfunctional esophagus until normal function and motility were regained. A crop
      support pressure bandage was placed in 4 birds to improve crop emptying into the
      proventriculus and to prevent crop distension. Although chelation therapy is the
      gold standard treatment for lead toxicosis, severe cases of lead-induced crop
      stasis are not acutely reversible with pharmaceuticals. In these condors,
      placement of a feeding tube was deemed prudent to ensure a viable enteric route
      of nutritional support during the standard treatment and recovery period in acute
      lead toxicosis with crop stasis.

PMID- 23156981
TI  - "Use of a locking compression plate as an external fixator for repair of a
      tarsometatarsal fracture in a bald eagle (Haliaeetus leucocephalus)".

PMID- 23156982
TI  - A few years out of veterinary school: are you happy as a veterinarian?

PMID- 23156983
TI  - HPLC analysis and cytotoxic activity of Vernonia cinerea.
AB  - The extracts of five Cambodian medicinal plants (Aganosma marginata, Dracaena
      cambodiana, Harrisonia perforata, Hymenodictyon excelsum and Vernonia cinerea)
      were evaluated in vitro for their cytotoxic activity against HT29 colon
      adenocarcinoma cells and HepG2 hepatoma cells, using the MTT assay. Among these
      five plants, Vernonia cinerea displayed potent cytotoxicity. One main
      sesquiterpene lactone, 8alpha-tigloyloxy-hirsutinolide-13-O-acetate was isolated
      from the whole plant of V. cinerea. This compound was active against both cancer
      cell lines (IC50 = 3.50 microM for HT29 and IC50 = 4.27 microM for HepG2). To
      quantify this compound in the plant, an analytical high-performance liquid
      chromatography (HPLC) method was developed and validated.

PMID- 23156984
TI  - Antiplasmodial activity of the ethnobotanical plant Cassia fistula.
AB  - In our ongoing investigation of new compounds with activity against malaria
      parasites, we tested the in vitro antiplasmodial activity of fractions and
      purified compounds from Cassia fistula L., a plant traditionally used by native
      populations of Tanzania, Zimbabwe, Mozambique and Brazil to treat malaria or
      symptoms associated with this disease. Crude extracts from leaves, bark and
      fruits were tested for their antiplasmodial activity against the chloroquine
      sensitive strain of Plasmodium falciparum (D10), where leaf extracts showed the
      highest activity. The chloroform extract of the leaves was further bioassay
      guided fractionated using a combination of centrifugal partition chromatography
      and flash column chromatography. Three main antiplasmodial principles, phytol (1)
      (IC50 18.9 +/- 0.60 microM), lutein (2) (IC50 12.5 +/- 0.35 microM), and di
      lineolylgalactopyranosyl-glycerol (DLGG) (IC50 5.8 +/- 0.27 microM) (3), were
      isolated and identified using spectroscopic methods. When the three active
      principles were tested for their cytotoxicity using a Chinese Hamster Ovarian
      (CHO) cell line, compound 3 showed very weak toxicity (IC50 75.9 +/- 0.28
      microM), while the other two compounds were nontoxic, even at the highest
      concentration tested. The study provides evidence to support the use of Cassia
      fistula as an antimalarial remedy and describes the antiplasmodial constituents
      from the leaves.

PMID- 23156985
TI  - Trichilone, a new C21 steroid from Trichilia connaroides.
AB  - Phytochemical investigation of the leaves of Trichilia connaroides led to the
      isolation of a new pregnane, trichilone (1), featuring a 2-methoxycyclopent-2
      enone moiety, along with a related known compound, 3beta,4alpha-dihydroxypregnane
      16-one (2). The structure of 1 was established on the basis of extensive
      spectroscopic analysis. Compound 1 showed significant root-growth inhibition
      activity against Amaranthus. mangostanus with an IC50 value of 23.1 ppm.

PMID- 23156986
TI  - Three novel immunosuppressive steroidal glycosides from the stems of Stephanotis
      mucronata.
AB  - Three novel and one known C21 steroidal glycosides were isolated from the stems
      of Stephanotis mucronata. Their structures were determined on the basis of
      chemical evidence and extensive spectroscopic methods. The four C21 steroidal
      glycosides displayed significant immunosuppressive activities in vitro.

PMID- 23156987
TI  - Optimization of carbon source for hairy root growth and withaferin A and
      withanone production in Withania somnifera.
AB  - This study optimized carbon sources in half MS liquid medium for maximum biomass
      accumulation and withanolides production in hairy root culture of Withania
      somnifera. The highest production of withaferin A and withanone was achieved when
      sucrose and sucrose+glucose were used individually as carbon sources. The hairy
      root suspension culture supplemented with a lower level of sucrose (2%) favored
      hairy root biomass accumulation (1.41 g DW) followed by sucrose+glucose (2+1)
      when compared with other carbon sources in half MS liquid medium after 40 days of
      culture. The hairy roots grown on sucrose (4%) enriched half MS liquid medium
      stimulated higher production of withaferin A (2.21 mg/g DW) and withanone (2.41
      mg/g DW) on the 40th day of culture, followed by sucrose+glucose (4+1%) compared
      with glucose, fructose, maltose and other combinations tested.

PMID- 23156988
TI  - Quantitative analysis of substituted N,N-dimethyl-tryptamines in the presence of
      natural type XII alkaloids.
AB  - This paper reports the qualitative and quantitative analysis (QA) of mixtures of
      hallucinogens, N,N-dimethyltryptamine (DMT) (1), 5-methoxy- (la) and 5-hydroxy
      N,N-dimethyltryptamine (1b) in the presence of beta-carbolines (indole alkaloids
      of type XII) ((2), (3) and (5)}. The validated electronic absorption
      spectroscopic (EAs) protocol achieved a concentration limit of detection (LOD) of
      7.2.10(-7) mol/L {concentration limit of quantification (LOQ) of 24.10(-7) mol/L)
      using bands (lambda max within 260+/-0.23-262+/-0.33 nm. Metrology, including
      accuracy, measurement repeatability, measurement precision, trueness of
      measurement, and reproducibility of the measurements are presented using N,N
      dimethyltryptamine (DMA) as standard. The analytical quantities of mixtures of
      alkaloids 4, 6 and 7 are: lambda max 317+/-0.45, 338+/-0.69 and 430+/-0.09 for 4
      (LOD, 8.6.10(-7) mol/L; LOQ, 28.66(6), mol/L), as well as 528+/-0.75 nm for 6 and
      7 (LOD, 8.2.10(-7) mol/L; LOQ, 27.33(3), mol/L), respectively. The partially
      validated protocols by high performance liquid chromatography (HPLC),
      electrospray ionization (ESI), mass spectrometry (MS), both in single and tandem
      operation (MS/MS) mode, as well as matrix/assisted laser desorption/ionization
      (MALDI) MS are elaborated. The Raman spectroscopic (RS) protocol for analysis of
      psychoactive substances, characterized by strong fluorescence RS profile was
      developed, with the detection limits being discussed. The known synergistic
      effect leading to increase the psychoactive and hallucinogenic properties and the
      reported acute poisoning cases from 1-7, make the present study emergent, since
      as well the current lack of analytical data and the herein metrology obtained
      contributed to the elaboration of highly selective and precise analytical
      protocols, which would be of interest in the field of criminal forensic analysis.

PMID- 23156989
TI  - HPLC analysis of stemokerrine and oxystemokerrine in the Thai medicinal plant
      Stemona kerrii.
AB  - A HPLC-UV method was developed and validated for determination of stemokerrine
      and oxystemokerrine in Stemona kerrii roots. The chromatographic separation was
      performed on a Hypersil BDS Cl8-column eluted with methanol: 50 mM ammonium
      acetate solution using a gradient system with a flow rate of 1 mL/min and
      detection at 300 nm. Stemokerrine and oxystemokerrine showed a linear
      relationship within the range of 0.5-100 microg/mL. The method was shown to be
      precise with a RSD <2%. The average percent recovery of stemokerrine was 101.6%
      and for oxystemokerrine 99.5%. Two samples of S. kerrii were analyzed and the
      average contents of stemokerrine and oxystemokerrine were 0.2 and 0.05%, w/w,
      respectively. The present work will provide a useful standardization method for
      S. kerrii raw materials for further pharmaceutical development.

PMID- 23156990
TI  - Identification of pavinane alkaloids in the genera Argemone and Eschscholzia by
      GC-MS.
AB  - The genera Eschscholtzia and Argemone (Papaveraceae) represent a rich source of
      pavinane alkaloids, the identification of which in alkaloid extracts is generally
      problematic without standards. The alkaloid extracts of three Argemone and four
      Eschscholtzia species were analyzed using GC-MS. The alkaloids were identified
      based on comparison of their mass spectra with commercial libraries, with
      reported data in the literature and with spectra of reference compounds. A total
      of 23 alkaloids of six structural types (pavinane, protopine, benzylisoquinoline,
      benzophenanthridine, aporphine and protoberberine) were identified. The
      fragmentation pathway of pavinane alkaloids was used for their identification. O
      Methylneocaryachine has been reported for the first time from a natural sources
      and the alkaloid pattern of Eschscholzia pulchella has been analyzed and
      described for the first time.

PMID- 23156991
TI  - Effect of piperine on the pharmacokinetics and pharmacodynamics of glimepiride in
      normal and streptozotocin-induced diabetic rats.
AB  - The effect of piperine on the pharmacokinetics and pharmacodynamics of
      glimepiride in normal as well as diabetic rats was studied. In normal and
      streptozotocin induced diabetic rats the combination of glimepiride with piperine
      increased all the pharmacokinetic parameters, such as Cmax, AUC0-n, AUCtotal,
      t1/2, and MRT, and decreased the clearance, Vd, markedly as compared with the
      control group. In pharmacodynamic studies, the combination of glimepiride with
      piperine provided significant protection against the diabetes induced alterations
      in the biochemical parameters. In addition, the combination of glimepiride with
      piperine also improved the total antioxidant status significantly in diabetic
      rats compared with piperine and glimepiride treated groups. The results revealed
      that a combination of glimepiride with piperine led to the enhancement of the
      bioavailability of glimepiride by inhibiting the CYP2C9 enzyme, which suggested
      that piperine might be beneficial as an adjuvant to glimepiride in a proper dose,
      in diabetic patients.

PMID- 23156992
TI  - In silico prediction of the cosmetic whitening effects of naturally occurring
      lead compounds.
AB  - The identification of tyrosinase inhibitors is important, not only for the
      treatment of skin hyperpigmentation disorders, such as melasma, but also for the
      production of cosmetic whitening effects. The aim of this study was the in silico
      prediction of the naturally occurring lead compounds in three commonly used skin
      whitening herbs: Ampelopsis japonica, Lindera aggregata, and Ginkgo biloba. The
      active ingredients responsible for the whitening effect of these herbs remain
      largely unknown. The tyrosinase binding affinities and skin permeation, skin
      irritancy, and corrosive properties of43 natural constituents of the three herbs
      were predicted by docking simulations using Surflex-Dock and the QSAR-based
      Dermal Permeability Coefficient Program (DERMWIN) and Skin Irritation Corrosion
      Rules Estimation Tool (SICRET) implemented in Toxtree. Nine constituents of the
      three herbs were found to have more advanced binding energies than the gold
      standard whitening agents, arbutin and kojic acid, but 40 were indicative of at
      least one skin sensitization alert, and many exhibited poor skin permeability.
      Linderagalactone c and (+)-n-methyllaurotetanine were found to have the strongest
      prospects for use in topical formulations, as they achieved high predicted
      tyrosinase binding scores and displayed good skin permeation properties and
      minimal potential for skin sensitization and irritation.

PMID- 23156993
TI  - Profiling flavonoid cytotoxicity in human breast cancer cell lines: determination
      of structure-function relationships.
AB  - Flavonoids have been shown to be cytotoxic to cancer cells. However, the
      mechanism of cytotoxicity has not been clearly defined. It has previously been
      reported that HER2/ERBB2, the estrogen receptor, progesterone receptor, and p53
      were required for flavonoid induced cytotoxicity in breast cancer cell lines. We
      have used a panel of breast cancer cell lines, known to contain as well as be
      deficient in these signaling pathways, to screen fourteen different flavonoids.
      Comparing the cytotoxicity for all flavonoids allows us to determine if a
      structure-functional relationship exists between cytotoxicity and flavonoid, and
      if a particular signaling pathway is required for cytotoxicity. We show that
      several flavonoids are cytotoxic to all cell lines including primary mammary
      epithelial cells tested. The cytotoxic flavonoids are also able to inhibit
      Mitochondrial Outer Membrane Permeability while at the same time stimulate ATP
      levels whereas the non-cytotoxic flavonoids are not able to do this. We also show
      that both cytotoxic and non-cytotoxic flavonoids can transverse the cell membrane
      to enter MDA-MB-231 cells at different levels. Finally, all flavonoids regardless
      of their cytotoxicity were able to induce some form of cell cycle arrest. We
      conclude that for flavonoids to be strongly cytotoxic, they must possess the 2,3
      double bond in the C-ring and we believe the cytotoxicity occurs through
      mitochondrial poisoning in both cancer and normal cells.

PMID- 23156994
TI  - Two new flavonoids from the seeds of Derris scandens.
AB  - Two new flavonoids, (2S)-3',4',5'-trimethoxyflavanone (1) and 2'-hydroxy-2,4
      dimethoxy-4'-O-[(E)-3,7-dimethyl-2,6-octadienyl]chalcone (2), together with a
      known pterocarpene, flemichapparin B (3), and a known rotenoid, dehydrodeguelin
      (4), were isolated from the seeds of Derris scandens. Their structures were
      determined by means of extensive 1D and 2D NMR spectral studies.

PMID- 23156995
TI  - Dihydroflavonol and flavonol derivatives from Macaranga recurvata.
AB  - Two new dihydroflavonol derivatives, macarecurvatins A and B, have been isolated
      from the leaves of Macaranga recurvata (Euphorbiaceaae), along with the known
      compounds diisoprenylaromadendrin, glyasperin A and broussoflavonol F. The
      structures of the new compounds were determined on the basis of spectroscopic
      evidence. Upon cytotoxic evaluation against P-388 cells, macarecurvatin B showed
      strong activity with an IC50 of 0.83 microM.

PMID- 23156996
TI  - Flavonoids bearing an O-arabinofuranosyl-(1-->3)-rhamnoside moiety from
      Cladocolea micrantha: inhibitory effect on human melanoma cells.
AB  - Eleven known triterpenes (alpha-amyrin, beta-amyrin, lupeol, and their respective
      acetates, 3-O-acetyl derivatives of betulinic, oleanolic, and ursolic acids,
      cycloartenol, and tirucall-7,24-dienol), two new flavonols presenting an uncommon
      interglycosidic O-(1-->3) linkage (kaempferol 3-O-alpha-L-arabinofuranosyl(1-->3)
      alpha-L-rhamnoside and quercetin 3-O-alpha-L-arabinofuranosyl-(1-->3)-alpha-L
      rhamnoside), beta-sitosterol, stigmasterol, quercetin, and gallic acid were
      isolated from the Amazonian medicinal mistletoe, Cladocolea micrantha Kuijt
      (Loranthaceae). Their structures were established by spectral methods and
      eventual chromatographic comparisons. The quercetin derivative was not cytotoxic
      to MV3 human melanoma cells, but was able, when administered at 1 microg/mL, to
      promote a twofold inhibition of the migration of the cells through the transwell
      system when compared with paclitaxel at 5 microM.

PMID- 23156997
TI  - Effect of seasonality on chemical composition and antibacterial and anticandida
      activities of Argentine propolis. Design of a topical formulation.
AB  - The effect of seasonality on Argentine propolis collected during one year on its
      phenolic and flavonoid content and on the growth of Gram-positive and Gram
      negative antibiotic resistant bacteria and Candida species was evaluated.
      Extracts of propolis samples collected in the summer and spring showed higher
      phenolic and flavonoid contents than the samples collected in other seasons (5.86
      to 6.06 mg GAE/mL and 3.77 to 4.23 mg QE/mL, respectively). The propolis
      collected in summer and autumn showed higher antibacterial activity (30
      microg/mL) than the other samples (MIC values between 30 and 120 microg/mL). No
      antibacterial activity was detected against Gram-negative bacteria. Also, these
      extracts were able to inhibit the development of five Candida species, with MFC
      values of 15-120 microg/mL. Pharmaceutical formulations containing the more
      active propolis extract were prepared. The hydrogel of acrylic acid polymer
      containing summer propolis extract as an antimicrobial agent showed
      microbiological, physical and functional stability during storage for 180 days.
      The pharmaceutical preparation, as well as the propolis extracts, was active
      against Candida sp. and antibiotic-multi-resistant Gram-positive bacteria. These
      results reveal that propolis samples collected by scraping in four seasons,
      especially in summer in Calingasta, San Juan, Argentina, can be used to obtain
      tinctures and hydrogels with antibacterial and antimycotic potential for topical
      use.

PMID- 23156998
TI  - Larvicidal activity of isoflavonoids from Muellera frutescens extracts against
      Aedes aegypti.
AB  - The biological activity of extracts from the leaves, bark and roots of Muellera
      frutescens, an Amazonian ichtyotoxic plant, were evaluated to find new
      environmentally safe insecticides. The n-hexane extracts of bark, leaf, and root
      showed a strong toxic activity against Aedes aegypti mosquito larvae. Bioguided
      fractionation of the bark extract led to the isolation of seven isoflavonoids
      (12a-hydroxyelliptone, elliptone, (-)-variabilin, rotenone, rotenolone, tephrosin
      and deguelin). Rotenone and deguelin are responsible for the larvicidal activity
      of the plant. M frutescens leaves contain up to 0.6%, w/w, deguelin. These
      results justify the traditional ichtyotoxic use of M frutescens. The leaves
      contain a relatively high proportion of deguelin and, therefore, can be
      considered as a renewable source of this environmentally friendly insecticidal
      isoflavonoid.

PMID- 23156999
TI  - Phenolic compounds in five Epilobium species collected from Estonia.
AB  - Epilobium species have been traditionally used as medicinal plants to treat
      benign prostate hyperplasia. The present study investigated the content of
      polyphenols, tannins, and flavonoids in Epilobium parviflorum Schreb., E.
      hirsutum L., E. adenocaulon Hausskn., E. montanum L., and E. palustre L. growing
      in Estonia. The total contents of polyphenols, tannins, and flavonoids were
      studied using UV spectroscopy with subsequent HPLC quantification of gallic acid,
      ellagic acid, and quercetin as marker compounds. All roots, stems, leaves, and
      flowers of the plants investigated contained comparable amounts of polyphenols,
      tannins, and flavonoids. There was a clear positive correlation between the
      contents of tannins and flavonoids in various plant parts. The content of these
      biologically active compounds suggests the use of E. parviflorum, E. hirsutum, E.
      adenocaulon, E. montanum, and E. palustre collected from Estonia as herbs both
      individually or as a blend.

PMID- 23157000
TI  - A new prenylated acetophenone from the root bark of Derris indica.
AB  - A new acetophenone, 1-[2,4-dihydroxy-5-(3-methylbut-2-enyl)phenyl]ethanone (1)
      was isolated from the root bark of Derris indica, along with 3,7,-dimethoxy-3',4'
      methylenedioxyflavone (desmethoxykanugin) (2), 5-methoxyfurano[4",5":6,7]flavone
      (pinnatin) (3), and 3'-hydroxyfurano[4",5":7,8]flavone (pongol) (4). The
      structures of these compounds were established by means of chemical and spectral
      studies. The occurrence of this prenylated acetophenone in D. indica is of
      biogenetic and chemotaxonomic significance.

PMID- 23157001
TI  - Phytotoxic furanocoumarins from the shoots of Semenovia transiliensis.
AB  - Discovery of novel, natural herbicides has become important to manage increasing
      weed resistance to synthetic herbicides and environmental issues. The systematic
      bioassay-guided fractionation and purification of the methylene chloride/methanol
      extract of the shoots of Semenovia transiliensis led to the isolation of several
      phytotoxic compounds. Lactuca sativa L. (lettuce, a dicot) and Agrostis
      stolonifera L. (bentgrass, a monocot) bioassays were used to identify and isolate
      the phytotoxic fractions. A number of furanocoumarin compounds isolated from S.
      transiliensis shoots were phytotoxic to both test species. These included
      psoralen, isopsoralen, heratomin, isopentenyloxyisobergapten, imperatorin,
      bergapten, xanthotoxin, heraclenin, and heraclenol. All the active secondary
      metabolites isolated from the shoots of S. transiliensis were furanocoumarins.
      Identification of these was accomplished using mass spectrometry and 1- and 2
      dimensional NMR techniques. Phytotoxic activity o f isolated compounds w a s
      evaluated in a dose-response manner from 0.3 to 1000 microM. Ingeneral, all of
      the compounds were more active on A. stolonifera than L. sativa. Bergaptin and
      xanthotoxin were the most active of the compounds, with moderate activity at 100
      microM. Imperatorin and xanthotoxin inhibited growth of Lemna paucicostata
      Hegelm. by 50% at 29 and 60 microM, respectively. Our results show that S.
      transiliensis is rich in furanocoumarins, which are probably involved in various
      aspects of the chemical ecology of the species. Unfortunately, the general
      cytotoxicity of furanocoumarins makes them an unlikely candidate for pesticide
      discovery.

PMID- 23157002
TI  - Chemoenzymatic synthesis of two new halogenated coumarin glycosides as potential
      antifungal agents.
AB  - Two new potential antifungal coumarin glycosides, 6-chlorocoumarin 7-O-beta-D
      glucopyranoside (1) and 7-hydroxy-4-trifluoromethyl-coumarin 5-O-beta-D
      glucopyranoside (2), were synthesized via enzyme-mediated glycosylation of the
      respective aglycone, 6-chloro-7-hydroxycoumarin and 5,7-dihydroxy-4
      trifluoromethylcoumarin, using transgenic hairy roots of Polygonum multiflorum.
      Instead of application of the isolated enzyme and exogenous sugar donors, hairy
      roots of P. multiflorum were successfully adapted as a whole-cell biocatalyst.

PMID- 23157003
TI  - Two new naphthoquinone derivatives from the stem bark of Callicarpa maingayi.
AB  - Two new naphthoquinones designated as 3alpha-hydroxy-2-(2-hydroxypropan-2-yI)
      9alpha-methoxy-2,3,3alpha,9alpha-tetra-hydronaphtho[2,3-b]furan-4,9-dione
      (callicarpa-quinone A, 1) and 5-hydroxy-2-(2-hydroxypropan-2-yl)naphtho[2,3
      b]furan-4,9-dione (callicarpaquinone B, 2) were isolated from the chloroform
      fraction of Callicarpa maingayi. Three other known compounds, identified as
      avicequinone-C (3), wodeshiol (4) and paulownin (5), were reported for the first
      time from this species. The structure elucidation of compounds was established by
      comprehensive 1D and 2D NMR spectroscopic analyses as well as EIMS, UV and IR
      spectral data. Compounds 1 and 2 were tested in vitro for their cytotoxic
      activity against human breast cancer MCF-7cells. Compound 2 exhibited strong
      cytotoxic activity with an IC50 value of 1.9 +/- 0.2 microM, while 1 showed
      moderate activity with an IC50 value of 25.0 +/- 4.3 microM.

PMID- 23157004
TI  - Novel sorbicillin analogues from the marine fungus Trichoderma sp. associated
      with the seastar Acanthaster planci.
AB  - Two novel sorbicillinoid analogues, (4'Z)-sorbicillin (1) and (2S)-2,3-dihydro-7
      hydroxy-6-methyl-2-[(E)-prop-1-enyl]-chroman-4-one (2), together with three known
      compounds, (2S)-2,3-dihydro-7-hydroxy-6,8-dimethyl-2-[(E)-prop-1-enyl]-chroman-4
      one (3), sorbicillin (4), and 2',3'-dihydrosorbicillin (5), were isolated from
      the culture broth of the fungus Trichoderma sp. associated with the seastar
      Acanthaster planci. Their structures were determined by analysis of the NMR and
      MS data. Compound I was the first example with a Z-configuration of the C-4'/C-5'
      double bond in the sorbyl side chain. Compounds 2 and 3 were uncommon monomeric
      sorbicillinoids with a cyclic sorbyl chain. 2, 3 and 5 showed moderate cytotoxic
      activities against various cancer cell lines.

PMID- 23157005
TI  - Cytotoxic bioactivity of some phenylpropanoic acid derivatives.
AB  - In this study, we synthesized a series of phenylpropanoic acid derivatives based
      on modifications at four selected points of the molecular scaffold. The in vitro
      antiproliferative activities of the compounds were examined in representative
      human solid tumor cell lines. A SAR was established pointing out the relevance of
      the substituents. The best activity profiles were obtained for the derivatives
      bearing more lipophilic esters (GI50 3.1-21 microM).

PMID- 23157006
TI  - Anti-Helicobacter pylori activities of natural isopentenyloxycinnamyl derivatives
      from Boronia pinnata.
AB  - In this study we investigated the anti-Helicobacter pylori activity of four
      isopentenyloxycinnamyl derivatives from the Australian shrub Boronia pinnata Sm.
      (Rutaceae), structurally related to boropinic acid: (E)-3-(4-(3-methylbut-2
      enyloxy)-3,5-dimethoxyphenyl)acrylaldehyde (1), boropinol C (2), boropinal (3)
      and boropinol A (4). In vitro growth of H. pylori strains 26695 and B128 was
      analyzed in liquid culture with increasing doses of these compounds. Bacterial
      morphology was visualized by scanning electron microscopy. The in vivo effects of
      the two most efficient molecules that reduced bacterial growth in vitro,
      compounds 3 and 4, were investigated on H. pylori gastric colonization in the
      mouse model. The presence of these compounds in the bacterial cultures led to
      alterations of bacterial surface and flagella. In vivo, both compounds 3 and 4 at
      250 microM reduced significantly the ability of H pylori to colonize the gastric
      mucosa of mice, compared with untreated ones. These data indicate that these
      natural isopentenyloxycinnamyl derivatives related to boropinic acid can be
      considered as novel antibacterial agents with anti-H. pylori activity.

PMID- 23157007
TI  - Thymofolinoates A and B, new cinnamic acid derivatives from Euphorbia thymifolia.
AB  - Two new cinnamic acid derivatives, thymofolinoates A (1) and B (2) have been
      isolated from the chloroform soluble fraction of Euphorbia thymifolia and their
      structures assigned from 1H and 13C NMR spectra, DEPT and by 2 D COSY, HMQCand H
      MBC experiments. In addition, p-hydroxy cinnamic acid(3), 5-hydroxy-6,7,8,4'
      tetramethoxy flavone (4), and 5-hydroxy-3',4',6,7,8-pentamethoxy flavone (5) have
      also been isolated for the first time from this species.

PMID- 23157008
TI  - Efficient counter-current chromatographic isolation and structural identification
      of two new cinnamic acids from Echinacea purpurea.
AB  - Two new cinnamic acids, 2-O-caffeoyl-3-O-isoferuloyltartaric (3), and 2, 3-di-O
      isoferuloyltartaric acid (5), along with three known caffeic acids, cichoric acid
      (1), 2-O-caffeoyl-3-O-feruloyltartaric acid (2) and 2-O-caffeoyl-3-O-p
      coumaroyltartaric acid (4), have been successfully isolated and purified from
      Echinacea purpurea. In this study, we investigated an efficient method for the
      preparative isolation and purification of cinnamic acids from E. purpurea by high
      speed counter-current chromatography (HSCCC). The separation was performed using
      a two-phase solvent composed of n-hexane-ethyl-acetate-methanol-0.5% aqueous
      acetic acid (1:3:1:4, v/v). The upper phase was used as the stationary phase and
      the lower phase as the mobile phase, with a flow rate of 1.6 mL/min. From 250 mg
      of crude extracts, 65.1 mg of 1, 8.3 mg of 2, 4.0 mg of 3, 4.5 mg of 4, and 4.3
      mg of 5 were isolated in one-step, with purities of 98.5%, 97.7%, 94.6%, 94.3%,
      and 98.6%, respectively, as evaluated by HPLC-DAD. The chemical structures were
      identified by electro spray ionization mass spectrometry (ESI-MS) and one- and
      two-dimensional NMR spectra. HSCCC was very efficient for the separation and
      purification of the cinnamic acids from

PMID- 23157009
TI  - Norlignans from Asparagus cochinchinensis.
AB  - A new norlignan glycoside, named iso-agatharesinoside (2), and its aglycone, iso
      agatharesinol (1), were isolated from the tuberous roots of Asparagus
      cochinchinensis. Their structures were established on the basis of spectral data,
      particularly by the use of 1D NMR and several 2D shift-correlated NMR pulse
      sequences (1H-1H COSY, HSQC, HMBC and ROESY).

PMID- 23157010
TI  - Novel application of Mahua (Madhuca sp.) flowers for augmented protease
      production from Aeromonas sp. S1.
AB  - The present study explored the utilization of Mahua (Madhuca sp.) flowers, a
      major non-timber forest product (NTFP) of India, as a low-cost, natural substrate
      for protease production under submerged fermentation. Bacterial strain Aeromonas
      sp. Si1, previously reported by us, was used as the protease producer. Using
      Mahua flower extract (MFE) as the medium additive, the protease production could
      successfully be enhanced by 5.6-fold (564.5 UmL-1) after 24 h of fermentation
      under optimized conditions compared with initial production of 99.9 UmL' in the
      absence of MFE. The cultural parameters for optimum production of protease were
      determined to be: incubation time-24 h; pH-7.0; MFE concentration-5% (v/v);
      inoculum size-0.3% (v/v) and agitation rate-200 rpm. The results obtained
      demonstrate the potential of cheaper and abundantly available Mahua flowers for
      induction of proteases, and thus offer a new approach for value addition to this
      biomass through industrial enzyme production.

PMID- 23157011
TI  - Chemical composition of the fatty oils of the seeds of Cleome viscosa accessions.
AB  - Fatty oils of the seeds of Cleome viscosa accessions from Delhi, Jaipur,
      Faridabad, Surajkund and Hyderabad were methylated and analyzed by GC and GC
      MS.The major fatty acids, identified as their methyl esters, of the oils from
      these five locations were palmitic acid (10.2-13.4%), stearic acid (7.2-10.2%),
      oleic acid (16.9-27.1%) and linoleic acid (47.0-61.1%). In addition, palmitoleic
      acid,octadec-(11E)-enoicacid, arachidic acid, eicosa-(11Z)-enoic acid, linolenic
      acid, heneicosanoic acid, behenic acid, lignoceric acid, pentacosanoic acid,
      hexacosanoic acid, 12-oxo-stearic acid, and the alkanes tetracosane, pentacosane,
      hexacosane, heptacosane, octacosane, nonacosane, triocontane, hentriacontane and
      dotriacontane, were also identified as minor and trace constituents in some of
      these oils.

PMID- 23157012
TI  - Essential oil and other constituents from Magnolia ovata fruit.
AB  - The volatile and non-volatile constituents of the unripe fruits of Magnolia ovata
      (A. St.-Hil.) Spreng. (Magnoliaceae) were studied. The essential oils were
      obtained by hydrodistillation of the fruit of two plant populations (A and B) and
      analyzed by GC/FID and GC/MS. The oil of sample A was rich in sesquiterpenes,
      mainly spathulenol (19.3%), while the oil of sample B showed a predominance of
      aliphatic compounds, mainly hexadecanoic acid (52.0%). Extracts of the dried
      fruit contained fourteen known compounds including nine lignoids (magnovatin A,
      magnovatin B, acuminatin, licarin A, oleiferin A, oleiferin C, kadsurenin M, 4-O
      demethylkadsurenim M and 7-epi-virolin), two sesquiterpene lactones (parthenolide
      and michelenolide) and three alkaloids (lysicamine, lanuginosine and O
      methylmoschatoline). Michelenolide, 7-epi-virolin and lisycamine are reported for
      the first time in the species, while the remaining compounds have already been
      reported in the leaves and/or trunk bark o f Magnolia ovata. Acetylation o f
      oleiferin A yielded a ne wcompound, acetyl oleiferin A, whose NMR data and that
      of michelenolide are furnished.

PMID- 23157013
TI  - Chemical composition of the essential oil of Zingiber zerumbet var. darcyi.
AB  - The chemical composition of essential oil obtained by hydrodistillation method
      from the rhizomes of Z. zerumbet var. darcyi was determined by GC and GC-MS.
      Thirty-three compounds, accounting for 93.6% of the oil were identified including
      twenty compounds in minor (0.1-0.6%) and eight in trace (<0.05%) amounts. The
      main compounds were zerumbone (69.9%) alpha-humulene (12.9%), humulene epoxide II
      (2.5%), caryophyllene oxide (1.1%) and camphene (1.9%). In this analysis, it has
      been found that the variety could be used as an additional new source of natural
      zerumbone besides Zingiber zerumbet. This is a first report on the analysis of Z.
      zerumbet var. darcyi oil.

PMID- 23157014
TI  - Compositions of the volatile oils of Citrus macroptera and C. maxima.
AB  - The essential oils obtained by hydrodistillation from the fresh peels of Citrus
      macroptera Montr. and C. maxima (Burm.) Merr. were analyzed by GC and GC/MS. The
      yields of oil ranged from 0.53% in C. macroptera to 0.13% in C. maxima cultivar
      (white). Forty-seven compounds were identified in the oils with limonene (55.3
      80.0%), dodecyl acrylate (2.2-8.0%), geranial (0.4-3.5%), trans-linalool oxide
      (1.0-2.8%), alpha-terpineol (0.7-2.3%), linalool (0.7-1.5%) and cis-linalool
      oxide (0.5-1.4%) identified as major compounds. The oil ofC. macroptera contained
      limonene (55.3%), beta-caryophyllene (4.7%) and geranial (3.5%) as main
      compounds. Similarly, oils from two C. maxima (pink and white) cultivars were
      rich in limonene (72.0-80.0%), dodecyl acrylate (8.0-7.2%) and nootkatone (1.6
      2.5%). C. maxima (pink and white) cultivars were found to contain higher amount
      of limonene (72.0 and 80.0%) as compared with C. macroptera (55.3%). The chemical
      compositions of the oils were found to be similar, but nootkatone (1.6-2.5%) was
      identified only in C. maxima cultivars.

PMID- 23157015
TI  - Chemotaxonomical markers in essential oil of Murraya koenigii.
AB  - The composition of the essential oils of Murraya koenigii (L.) Spreng, cultivated
      at six locations in Peninsula Malaysia and Borneo are presented. The oils were
      obtained from fresh leaves by hydrodistillation and analyzed by gas
      chromatography-mass spectrometry (GC-MS); 61 compounds were identified, of which
      eleven were present in all the specimens analyzed. The two major volatile
      metabolites were identified as beta-caryophyllene (16.6-26.6%) and alpha-humulene
      (15.2-26.7%) along with nine minor compounds identified as beta-elemene (0.3
      1.3%), aromadendrene (0.5-1.5%), beta-selinene (3.8-6.5%), spathulenol (0.6
      2.7%), caryophyllene oxide (0.7-3.6%), viridiflorol (1.5-5.5%), 2
      naphthalenemethanol (0.7-4.8%), trivertal (0.1-1.0%) and juniper camphor (2.6
      8.3%). The results suggest that beta-caryophyllene and alpha-humulene could be
      used as chemotaxonomical markers for Malaysian M. koenigii, hence these specimens
      could be of the same stock and different from the ones in India, Thailand and
      China.

PMID- 23157016
TI  - Essential oil composition and antibacterial activity of Anthemis mixta and A.
      tomentosa (Asteraceae).
AB  - In the present study the chemical composition of the essential oils from aerial
      parts and roots of Anthemis mixta L. and A. tomentosa L. was evaluated by GC and
      GC-MS, and their antibacterial activity tested against ten bacterial species.
      Hexadecanoic acid (15.2%) was recognized as the main constituent ofA. mixta,
      together with tau-cadinol (6.7%), while in both aerial parts and roots of A.
      tomentosa nonacosane (21.9% and 20.7%), heptacosane (8.1% and 6.0%), hexadecanoic
      acid (8.1% and 27.1%) and hexahydrofarnesylacetone (6.8% and 5.5%) prevailed. The
      oils from aerial parts of both species showed a good activity against Gram
      positive bacteria. These results suggest that the plants could be potentially
      used in food manufacture and cosmetology as preservative agents or in medicine as
      new antibiotics.

PMID- 23157017
TI  - Antifungal and antibacterial activity of the essential oil of Chamaecyparis
      lawsoniana from Spain.
AB  - The essential oils extracted from the young stems and leaves of Chamaecyparis
      lawsoniana (A.Murray) Parl. have been analysed by Gas Chromatography and Gas
      Chromatography coupled to Mass Spectrometry. A total of 66 compounds were
      identified representing around the 99% of the total oil. The oil was richer in
      monoterpenes than in sesquiterpenes. The only main component was limonene with a
      percentage composition of 77.7%. The rest of compounds that contribute to the
      fragrance had percentage composition lower that the 3.0%: p-cymen-7-ol (3.0%),
      myrcene (2.4%), camphor (2.1%), delta-elemene (1.6%), oplopanonyl acetate (1.6%),
      methyl perillate (1.3%), terpinen-4-ol (1.0%) and beta-oplopenone 1.0%. The
      antibacterial and antifungal activity of this oil was also tested against
      different microorganisms. The only fungus tested, Candida albicans, was very
      sensitive to the treatment with an inhibition halos of 20mm. The oil was more
      effective with the Gram (+) than with Gram (-) bacteria. The inhibition halos
      were 12mm, 12-13mm and 12-13mm for Bacillus subtilis, Staphylococcus aureus and
      Micrococcus luteus respectively. We report new data of the antibacterial and
      antifungal activity of the essential oil of this species. The essential oil of C.
      lawsoniana could be considered as a good natural antibacterial and antifungal
      agent.

PMID- 23157018
TI  - Chemical composition and biological activities of essential oil from Hyptis
      crenata growing in the Brazilian cerrado.
AB  - Essential oils from species of the genus Hyptis are well-known for their
      significant biological properties, including antimicrobial and acaricidal
      activities. The essential oil from the aerial parts of H. crenata was obtained by
      hydrodistillation; bomeol (17.8%), 1,8-cineol (15.6%) and p-cimene (7.9%) were
      characterized by GC-MS as its major constituents. The essential oil was evaluated
      in vitro for its antimicrobial activities against six fungal and five bacterial
      strains, by measuring the respective MICs, MFCs and MBCs, using broth
      microdilution methods. The strongest bactericidal activities were shown against
      Staphylococcus aureus and Enterococcus faecalis, while the strongest fungicidal
      activities were against Cryptococcus neoformans, Candida glabrata and Candida
      tropicalis. The oil was also assessed for its anti-tick properties and, at a
      concentration of 2.5%, it significantly inhibited in vivo oviposition of engorged
      females of the cattle tick Rhipicephalus (Boophilus) microplus, using the adult
      immersion test., with an effectiveness of 94.4%.

PMID- 23157019
TI  - Larvicidal activity against Aedes aegypti of essential oils from northeast
      Brazil.
AB  - The larvicidal activities of essential oils from the leaves of Artemisia vulgaris
      L., Cymbopogon flexuosus (Nees ex Steud.) Wats. and Piper tuberculatum Jacq. were
      evaluated using third-instar larvae of Aedes aegypti. The essential oils were
      obtained by hydrodistillation and analyzed by GC and GC-MS. The essential oil of
      P. tuberculqatum had the lowest LC50 value (106.3 +/- 2.2 microg/mL), followed by
      that of A. vulgaris (114.1 +/- 1.7 microg/mL) and C. flexuosus (121.6 +/- 0.8
      micro/mL). The results show that these essential oils may be potent sources of
      natural larvicides.

PMID- 23157020
TI  - Composition and antipseudomonal effect of essential oils isolated from different
      lavender species.
AB  - The aims of our research include the phytochemical characterization of the
      essential oils extracted from different lavender species (Lavandula vera L., L.
      intermedia L., L. pyrenaica DC., and L. stoechas subsp. stoechas) that are
      important from therapeutic and economic aspects, as well as the optimization of
      the tube dilution method for microbiological investigation of the effect of
      essential oils on the selected Pseudomonas strain. The chemical and percentage
      compositions of the essential oils were analysed by gas chromatography (GC) and
      gas chromatography-mass spectrometry (GC-MS). The main component of the essential
      oils in the majority of lavender species was linalool, while L-fencone was
      identified in the largest amount in L. stoechas subsp. stoechas. Tube dilution is
      one of the most frequently used methods for microbiological investigation. Its
      advantages are that it is easy to perform and provides information about minimum
      bactericidal concentration (MBC). Because of the lipophilic character of
      essential oils, the tube dilution method should be optimized for the detection of
      antibacterial activity of these plant extracts, and, therefore, emulsions
      containing 0.2% polysorbate 80 were prepared from the samples. In each of the
      eight investigated essential oils an inhibitory effect was detected, and MBC
      values were in the range 12.5-50 microL/mL in seven cases.

PMID- 23157022
TI  - Antimicrobial activity of blended essential oil preparation.
AB  - Antimicrobial activities of two blended essential oil preparations comprising
      lavender oil, petigrain oil, clary sage oil, ylang ylang oil and jasmine oil were
      evaluated against various pathogenic microorganisms. Both preparations showed
      antimicrobial activity in the agar disc diffusion assay against the Gram-positive
      bacteria, Staphylococcus aureus ATCC6538 and S. epidermidis isolated strain, the
      fungus, Candida albicans ATCC10231, and the Gram-negative bacterium, Escherichia
      coli ATCC25922, but showed no activity against Pseudomonas aeruginosa ATCC9027.
      The minimum inhibitory concentration (MIC) of these preparations was evaluated.
      By the broth microdilution assay, preparation 1, comprising lavender oil, clary
      sage oil, and ylang ylang oil (volume ratio 3:4:3), exhibited stronger
      antimicrobial activity than preparation 2, which was composed of petigrain oil,
      clary sage oil, and jasmine oil (volume ratio 3:4:3). Moreover, the sum of the
      fractional inhibitory concentrations (Sigma fic) of preparation 1 expressed a
      synergistic antimicrobial effect against the tested microorganisms (Sigma fic<l).
      The blended essential oil preparations, characterized for their components by
      GC/MS, contained linalyl acetate, and linalool as major components. Our
      experiments showed that the differential antimicrobial effect of either blended
      oil preparations or single/pure essential oils may be influenced by the amount of
      linalool and linalyl acetate, and the number of active components in either the
      blended preparations or single/pure essential oils. In addition, blended oil
      preparations expressed synergistic antimicrobial effect by the accumulation of
      active components such as linalool and linalyl acetate and combining active
      constituents of more than one oil.

PMID- 23157021
TI  - Essential oil of Croton argyrophylloides: toxicological aspects and vasorelaxant
      activity in rats.
AB  - Croton argyrophylloides Muell. Arg. is widely used in Brazilian folk medicine to
      treat diabetes and venereal diseases. This study examined the acute toxicity and
      cytotoxicity of the essential oil of C. argyrophylloides (EOCA). In addition,
      vascular effects of the EOCA have been examined. In mice, an oral acute toxicity
      test revealed that EOCA could be considered as a non toxic essential oil since it
      showed a very high LD50 (9.84 +/- 0.01 g/kg). In the brine shrimp (Artemia
      salina) cytotoxic assay, the LC50 value of EOCA was 275 [165-534] microg/mL. EOCA
      (1-1000 microg/mL) relaxed isolated endothelium-intact aortic rings precontracted
      with phenylephrine with an IC50 value of 126.7 [89.8-163.7] microg/mL. In rat
      mesenteric bed preparations precontracted with phenylephrine, EOCA (1-300
      microg/mL) also induced a reversible, vasodilator effect with an IC50 value of
      46.0 [33.3-58.7] micro/mL. It is concluded that EOCA is a very interesting agent
      from the point of view of the possibility of therapeutic application. This is
      because, whilst showing a very small acute toxicity, EOCA also showed maximal
      efficacy as a vascular antispasmodic agent with a pharmacological potency similar
      to that of other Croton species essential oils.

PMID- 23157023
TI  - Understanding the physiology of folliculogenesis serves as the foundation for
      perfecting diagnosis and treatment of ovulatory defects.
AB  - PURPOSE: To discuss updated physiologic information concerning the mechanism of
      folliculogenesis. METHODS: Physiology studies involving the growth of primordial
      follicular growth and pre-antral growth to the development of the corpus luteum
      are discussed. RESULTS: Benefits in aiding fertility potential and pitfalls of
      these drugs in preventing embryo implantation are discussed with reference to the
      physiologic processes required for folliculogenesis. CONCLUSIONS: Knowledge of
      the physiology of folliculogenesis can provide further understanding of luteal
      function when taking follicle maturing drugs and complications, as premature
      luteinization and the luteinized unruptured follicle syndrome. Also, this
      knowledge helps to create novel therapies to prevent ovarian hyperstimulation
      syndrome, endometrial receptivity defects, and treating women with diminished
      oocyte reserve.

PMID- 23157024
TI  - ICSI cycle outcomes in oligozoospermia.
AB  - AIM: The aim of this study was to evaluate the sole effect of sperm concentration
      on fertilization, embryo quality and pregnancy rates in patients undergoing ICSI
      cycles. MATERIALS AND METHODS: 560 ICSI cycles performed for male factor
      infertility were divided into four groups according to sperm concentration
      retrospectively. Group 1 consisted of 86 couples whose sperm concentration was
      less than 1x10(6), group 2 consisted of 169 couples whose sperm concentration
      ranged between 1x10(6) and 5x10(6), group 3 consisted of 95 couples whose sperm
      concentration ranged between 5x10(6) and 10x10(6) and group 4 consisted of 210
      couples whose sperm concentration ranged between 10x10(6) and 20x10(6). RESULTS:
      Fertilization rate was significantly lower in the first three groups compared to
      the last group (p<0.05). The first three groups were comparable with each other.
      There were no differences according to ovarian response to stimulation, embryo
      quality and clinical pregnancy rates between the four groups. CONCLUSION: Lower
      sperm concentration has detrimental effects on the outcomes of ICSI cycles. This
      situation is more evident in men with severe and extremely severe
      oligozoospermia.

PMID- 23157025
TI  - The role of sperm banking in fertility preservation.
AB  - OBJECTIVE: To investigate factors that influence sperm banking before cancer
      therapy and assess the use and disposal of banked sperm after cancer treatment.
      STUDY DESIGN: Database exploratory study combined with questionnaire survey of a
      cohort of 55 men who cryopreserved their sperm at an Andrology Clinic. MAIN
      OUTCOME MEASURE(S): Rate of use, disposal and abandonment of banked sperm,
      current fertility, and patient satisfaction with sperm banking. RESULTS: Using
      logistic regression, we analyzed the factors associated with use and disposal of
      banked sperm, current fertility status, reproductive outcomes and quality of life
      in 55 survivors of cancer therapy who cryopreserved sperm at our facility. Most
      (93%) of the patients undergoing sperm banking before cancer treatment did not
      use their samples and 33% requested sperm disposal following completion of cancer
      therapy. Married status and fatherhood before cancer therapy were associated with
      higher rates of sperm disposal. Sperm disposal was requested because the subjects
      remained fertile, spontaneously fathered a child, or completed their family. The
      families of four patients (7%) who died from their cancer also requested disposal
      of the stored sperm. Six (11%) patients could not be located or failed to contact
      the clinic and were considered to have abandoned their banked sperm. Only 7% of
      the patients used their cryopreserved sperm for assisted reproduction. Most of
      the patients that banked sperm achieved pregnancy with their partners through
      spontaneous conception compared to through the use of cryopreserved sperm.
      CONCLUSIONS: The rates of disposal and abandonment of banked sperm were high
      following cancer therapy. Retention of fertility appears to contribute to the low
      utilization of banked sperm, which emphasizes the need for appropriate consent
      and directives regarding disposal of unused cryopreserved sperm.

PMID- 23157026
TI  - Cesarean section with relative indications versus spontaneous vaginal delivery:
      short-term outcomes of maternofetal health.
AB  - AIM: The aim of the study was to compare maternal and perinatal mortality and
      short-term outcomes of maternal and perinatal health between a cesarean group
      with relative indications and a vaginal delivery group. METHODS: A total of 1,119
      patients were included; 582 were delivered by spontaneous vaginal birth and 537
      delivered by cesarean section without labor. The indication for cesarean section
      was tocophobia and fear of childbirth for all patients. Maternal and perinatal
      morbidity and mortality were compared between the groups. RESULTS: No maternal
      mortality was recorded. Maternal morbidity was significantly lower in the vaginal
      birth group than the cesarean group (7 vs 30, p<0.05). Perinatal mortality (2 vs
      0) and perinatal morbidity were not significantly different between the two
      groups (33 vs 17). The vaginallly delivered group had significantly higher
      newborn hospitalization rates than the cesarean group (p<0.05), but
      hospitalization time did not differ. Newborns with the first minute Apgar score
      below 7 were higher in the cesarean group (p<0.05). Fifth minute Apgar scores and
      umblical cord pH values were similiar. Cesarean neonates weighed more than
      vaginally delivered ones (p<0.05). CONCLUSION: Short-term maternal complications
      were more frequently seen in cesarean deliveries with relative indications than
      spontanous vaginal deliveries but no difference was found in perinatal mortality
      and morbidity. There is a clear need for research on health outcomes for mothers
      and infants associated with cesarean delivery without any medical indication.

PMID- 23157027
TI  - Transient ligation of umbilical vessels elevates placental tissue oxygen index
      (TOI) values measured by near-infrared spectroscopy (NIRS) in clawn miniature pig
      animal model.
AB  - We recently found a significant elevation in placental tissue oxygen index (TOI)
      values in cases of fetal growth restriction using near-infrared spectroscopy
      (NIRS), indicating high oxygenation in the placental tissue. We hypothesized that
      insufficient fetoumbilical blood flow is causatively associated with high
      oxygenation levels in placental tissue. We transiently (for 15 sec) ligated the
      whole umbilicus, umbilical arteries, or veins of pregnant Clawn miniature pigs
      (102-113 days of gestation) and assessed the changes in TOI values of the
      placenta and fetus. The ligation significantly increased placental TOI values
      (p<0.01, respectively), but concomitantly decreased fetal TOI values (p<0.01,
      respectively), suggesting a decline in oxygen inflow from the maternal to fetal
      circulation in the placental tissue to be causative of the elevated placental TOI
      values. These observations suggest the promising clinical use of placental TOI
      values measured noninvasively by the transabdominal application of NIRS to assess
      the fetoplacental circulation.

PMID- 23157028
TI  - Endometrial polyps and their relationship in the pregnancy rates of patients
      undergoing intrauterine insemination.
AB  - PURPOSE: To evaluate the effect of the presence of endometrial polyps (EP) on
      pregnancy rates and how polypectomy could affect pregnancy rates in women
      scheduled for intrauterine insemination (IUI). METHODS: The study included
      patients who had attended the Second Department of Obstetrics and Gynecology of
      the University of Athens from April 2003 to October 2008 for infertility
      treatment and were candidates for IUI. In these women the presence of an
      endometrial polyp had been already diagnosed during the infertility evaluation.
      The study group consisted of 86 women who, following the diagnosis of endometrial
      polyp, had agreed to have the polyps removed hysteroscopically prior to the IUI.
      The control group consisted of 85 women, who despite the fact that the presence
      of an endometrial polyp had been previously diagnosed and its removal suggested,
      elected not to have the polyp removed. We used statistical analysis to check what
      effect the removal of the polyp had on the total number of pregnancies. RESULTS:
      There was a statistically significant difference in cumulative pregnancy rates
      between the two groups. The group that underwent polyp removal had higher
      pregnancy rates as compared to the one that the polyps were left intact.
      CONCLUSIONS: We propose that hysteroscopic polypectomy of any size appears to
      improve fertility in women with otherwise unexplained infertility.

PMID- 23157029
TI  - Assessment of fetomaternal hemorrhage by Kleihauer-Betke test, flow cytometry and
      alpha-fetoprotein after invasive obstetric procedures.
AB  - PURPOSE: The aim of this study was to evaluate the passage of fetal red blood
      cells to the maternal circulation, after invasive obstetric procedures, through
      the Kleihauer-Betke test, flow cytometry and by measurement of maternal serum
      alpha-fetoprotein level. METHODS: This prospective descriptive study with
      patients submitted to amniocentesis, cordocentesis, chorionic villus sampling
      (CVS), amnioreduction and ventriculoamniotic shunt was performed for karyotype
      analysis, treatment of hydrocephalus and polyhydramnios and to assess fetal lung
      maturity. Maternal blood samples were collected before and 60 minutes after the
      invasive obstetric procedure to search for fetal erythrocytes using the Kleihauer
      Betke test, flow cytometry and serum alpha-fetoprotein measurement. RESULTS: Ten
      invasive obstetric procedures were performed. The mean age of the patients was
      29.2 years and the mean gestational age was 29.6 weeks. The procedures were: five
      amniocenteses, two cordocenteses, one CVS, one ventriculo-amniotic shunt and one
      amnioreduction with cephalocentesis. The indications for the procedures were:
      karyotype analysis in five patients, fetal lung maturity assessment in two
      patients, amnioreduction in one patient, fetal hydrocephalus shunt in one patient
      and polyhydramnios related to hydranencephaly in one patient. Regarding the path
      of puncture, three procedures were accomplished through the placenta and seven
      apart from it. All punctures were successful at the first attempt. There was no
      significant increase of fetal erythrocyte quantity in maternal blood samples
      using the Kleihauer-Betke test. After cordocentesis, a significant increase of
      fetal erythrocytes was detected by flow cytometry and serum alpha-fetoprotein
      measurement. CONCLUSION: Invasive obstetric procedures during prenatal care are
      safe when performed by experienced professionals using adequate techniques, with
      minimal chance of passage of fetal erythrocytes from the fetal compartment.

PMID- 23157030
TI  - Foetal monitoring during labour: practice versus theory in a region-wide
      analysis.
AB  - PURPOSE: To evaluate cardiotocography (CTG) alone versus CTG and ST-analysis
      (STAN) in daily obstetric practice in a complete region. METHODS: Prospective
      registration in the region of Flanders in combination with standard registration
      of perinatal outcome. RESULTS: Of 62,606 term deliveries registered, 57,141
      (91.3%) were available for complete analysis. In 50,748 (88.8%) CTG alone and in
      6,393 (11.6%) CTG+STAN was used. STAN was used significantly more in case of
      hypertension, diabetes and induction of labour and was associated both in
      univariate and multivariate analysis with significantly more secondary caesarean
      section for suspected foetal distress, instrumental vaginal delivery, low Apgar
      score and need for neonatal intensive care. There was no difference in perinatal
      death or asphyxia. CONCLUSION: ST-analysis versus CTG results in more caesarean
      sections, instrumental vaginal deliveries and neonatal intensive care. This can
      not be explained solely by its use in more complicated cases as in multivariate
      analysis including hypertension, diabetes and induction of labour ST analysis
      persists as a significant factor. We hypothesise that this could be explained by
      less well trained users not adhering to STAN-guidelines.

PMID- 23157031
TI  - Effect of epidural analgesia on labor times and mode of delivery: a prospective
      study.
AB  - PURPOSE: To assess changes in labor times and delivery outcome in low-risk women
      requesting pain relief and undergoing epidural analgesia, according to the
      epidural analgesia schemes. MATERIALS AND METHODS: Prospective observational
      study of 499 low-risk women with epidural analgesia. Speed of dilatation (SD)
      (centimeters of dilatation / hours), speed of lowering of the fetal head through
      maternal pelvis (SL) (centimeters in lowering / hours), time of active phase of
      labor (TA), cesarean section (CS), vacuum application (VA) were dependent
      variables in multivariable linear and logistic regressions. RESULTS: Dilution of
      ropivacain, fentanyl amount, and volume of the first dose of epidural analgesia
      did not seem to affect labor times. Epidural analgesia with schemes used in this
      study favored both the dilatation and the fetal head lowering through maternal
      pelvis. Every five minutes from the first dose of epidural to the last top-up, SD
      decreased by about 13% (p=0.002), SL decreased by about 14% (p<0.001), and TA
      increased by about 40% (p<0.001). Additionally, every five minutes from the first
      dose of epidural to the last top-up, the odds of an operative vaginal birth
      (vacuum) increased by 0.7% (p<0.001). Increasing of number of top-ups
      independently caused a reduction in odds of undergoing CS (odds ratio 0.434; C.I.
      95% 0.219-0.859, p=0.017), without influencing labor times. CONCLUSION: Epidural
      analgesia in patients requesting pain relief favors normal course of labor if it
      is not discontinued or delayed.

PMID- 23157032
TI  - Effect of combined oral contraceptive use on platelet volume in women at
      reproductive age.
AB  - INVESTIGATION: Combined oral contraceptives use is associated with an increased
      risk of developing venous and arterial thromboembolic events. Platelet size,
      measured as mean platelet volume (MPV), is associated with platelet reactivity.
      METHODS: Ninety-five women using oral contraceptives for contraception were
      investigated retrospectively. The patients' blood pressure, pulse and
      hematological values at application and at the sixth month were evaluated
      retrospectively. RESULTS: There was no difference between the values of blood
      pressure (systolic and diastolic), pulse, hematological values (which contain
      leukocytes, platelets and mean platelet volume) at application and at the sixth
      month. CONCLUSION: We determined that using oral contraceptives for contraception
      did not change MPV values in young women.

PMID- 23157033
TI  - Modified repeated intracyclic clomiphene citrate therapy after conventional
      clomiphene therapy.
AB  - PURPOSE OF INVESTIGATION: We compared modified repeated intracyclic clomiphene
      citrate therapy (RICCT) to gonadotropin therapy to determine whether this
      modified regimen was an effective alternative after conventional clomiphene
      therapy. METHODS: Patients with ovulation disorder received treatment with
      modified RICCT and gonadotropin, and ovulation, pregnancy, total drug cost, and
      adverse effects were compared. RESULTS: Among a total of 16 patients, 14
      successfully ovulated after modified RICCT and 11 ovulated after gonadotropin
      therapy; two did not respond to either therapy. The total drug cost was US
      $36.3+/-17.9 for modified RICCT, which was significantly lower than the cost of
      gonadotropin therapy, US $213.9+/-100.4 (p=0.0001). CONCLUSIONS: Because modified
      RICCT does not require the discomfort of daily injection and has excellent
      ovulation-inducing effects, it is a useful treatment after conventional
      clomiphene therapy.

PMID- 23157034
TI  - The role of hypertension, body mass index, and serum leptin levels in patients
      with endometrial hyperplasia during premenopausal period.
AB  - OBJECTIVES: to investigate whether body mass index (BMI), hypertension (HTN),
      diabetes, age, and physical activity can be considered risk factors for
      endometrial simple hyperplasia in premenopausal women. Furthermore this study was
      undertaken to determine whether serum concentration of leptin in patients with
      BMI>or= 30 kg / m2 with endometrial hyperplasia deviate from values in patients
      with normal endometrium. MATERIALS AND METHODS: The authors enrolled 167
      hyperplasia cases and 282 controls. Demographic characteristics and data on age,
      diabetes, hypertension, BMI, physical activity, and anthropometric parameters
      were collected. Leptin concentration in serum was measured with immunoenzymatic
      test kit from IBL. Univariable and multivariable analysis were performed to
      verify the association among age, HTN, BMI, physical activity, diabetes, and the
      presence of uterine hyperplasia. Furthermore the authors evaluated the
      correlation between BMI and leptin level (with Pearson's linear correlation) in
      women with simple hyperplasia and in controls. RESULTS: The prevalence of
      hyperplasia found was 34.4%. The following factors were independently associated
      with increased risk of endometrial hyperplasia: HTN (odds ratio 3.19, 95%
      confidence interval 1.20-8.48, p<0.020) and BMI>or=30 Kg/m2 (odds ratio 6.43, 95%
      confidence interval 3.92-10.53, p<0.000). Mean leptin concentration in serum was
      higher in patients who had endometrial hyperplasia than in controls (p<0.005) and
      the leptin levels depended on BMI. CONCLUSIONS: The following are risk factors
      for endometrial hyperplasia in premenopausal women: BMI>or=30 kg/m2 and HTN
      (blood pressure>or=130/85 or in therapy). Leptin appears to participate in
      proliferative processes of the endometrium, depending on BMI. Current guidelines
      may need to be reconsidered.

PMID- 23157035
TI  - Effect of uterine artery blood flow on recurrent pregnancy loss.
AB  - We investigated the effect of uterine artery blood flow on recurrent pregnancy
      loss. One hundred and twelve patients admitted to our clinic were included in the
      prospective study. The study group consisted of 28 cases with a history of three
      miscarriages before the 20th gestational week, and the control group consisted of
      cases with at least one prior live birth without any history of miscarriage or
      poor obstetric outcome. The mean pulsatility index (PI) , resistance index (RI)
      and systolic/diastolic ratio (S/D ratio) values of the uterine artery were
      measured between the 18th and 23rd days of the menstrual cycle via transvaginal
      Doppler ultrasonography. No statistically significant difference could be
      detected regarding uterine artery PI (p=0.703), RI (p=0.333), and S/D (p=0.403)
      values between the study group and the control group (p>0.05). In order to
      clearly determine etiologic causes of recurrent pregnancy loss, new randomized
      and controlled clinical trials with large patient populations are needed.

PMID- 23157036
TI  - Vulvodynia: a case series of a poorly recognized entity.
AB  - Vulvodynia remains a poorly recognized entity with unclear pathogenesis. In a
      case series of six patients with vulvodynia over a five-year period in a tertiary
      university hospital, we describe the clinical features, the diagnostic
      procedures, the impact on each patient's emotional status and discuss the
      necessity and efficacy of the chosen treatment options in accordance with the
      current therapeutic guidelines.

PMID- 23157037
TI  - Clinical importance of detection of bacterial vaginosis, trichomonas vaginalis,
      candida albicans and actinomyces in Papanicolaou smears.
AB  - OBJECTIVE: The aim of this study was to determine the role of Papanicolaou (pap)
      smears in the diagnosis of lower genital tract infections. MATERIALS AND METHODS:
      A retrospective study was planned by reviewing charts of patients for trichomonas
      vaginalis, bacterial vaginosis, actinomyces, candida and nonspecific vaginitis.
      RESULTS: Charts of 9,080 patients were reviewed and 1,733 women had a diagnosis
      of lower genital tract infection in the pap smear or had had a clinically treated
      lower genital tract infection. Only 33.5%, 30.4%, 43.3%, and 0% of patients with
      bacterial vaginosis, trichomonas vaginalis, candida and actinomyces, respectively
      on pap smear were diagnosed and treated clinically. Postmenopausal patients had a
      higher rate of trichomonas vaginalis infection and a lower rate of candida
      infection when compared to women of the reproductive age group. Patients using an
      intrauterine device for contraception had a statistically significantly increased
      rate of trichomonas vaginalis and candida infection when compared to women using
      other contraceptive methods or those who were not using any contraception.
      CONCLUSIONS: Finding trichomonas vaginalis, bacterial vaginosis and actinomyces
      infections in pap smears might be considered an indication for treatment without
      performing other diagnostic tests. Treatment of asymptomatic infections can
      prevent complications in selected patients. Candida can be a commensal bacteria
      in the vagina, therefore asymptomatic patients may not require treatment.
      Detection of a higher rate of trichomonas vaginalis and candida infection in IUD
      users shows that IUDs can increase the risk of vaginal infections and associated
      complications.

PMID- 23157038
TI  - The impact of six-month tibolone postmenopausal treatment on cell adhesion
      molecules levels.
AB  - PURPOSE: The aim of the present study was to evaluate the effects of tibolone on
      inter-cellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1
      (VCAM-1), inter-cellular adhesion molecule-2 (ICAM-2) and P-selectin levels in
      healthy postmenopausal women. METHODS: This prospective study included 25
      postmenopausal women, complaining of hot flashes, assigned in two groups. Fifteen
      women received tibolone (dosage of 2.5 mg per day for six months) and ten women
      did not receive any therapy, according to their personal preference. Basal
      control included complete medical history, anthropometrics, clinical examination,
      and blood sampling to perform hormonal, biochemical, hematological testing and
      ICAM-1, ICAM-2, VCAM-1 and P-selectin measurements. Evaluation was repeated in
      three and six months. RESULTS: There was no significant difference in ICAM-1,
      VCAM-1, ICAM-2, P-selectin, homocysteine, total cholesterol, HDL, LDL, and
      triglyceride concentrations between the women of the two groups after either
      three or six months of treatment. However, a significant reduction in the
      frequency and intensity of hot flashes was noted in both groups. CONCLUSIONS:
      Tibolone does not have any adverse effects on cell adhesion molecule levels which
      primarily affect atherosclerotic processes or on triglyceride and homocysteine
      concentrations. These results may support the view that tibolone could be
      considered a safe treatment, regarding its impact on the endothelium, in healthy
      postmenopausal women.

PMID- 23157039
TI  - Are alanine, cysteine, glycine and valine amino acids the cause of non-immune
      hydrops fetalis?
AB  - Our objective was to measure amniotic fluid amino acid concentrations in pregnant
      women diagnosed as having fetuses with non immune hydrops fetalis in the second
      trimester of pregnancy. Twenty-three pregnant women who had fetuses with non
      immune hydrops fetalis detected by ultrasonography (non immune hydrops fetalis
      group) in the second trimester and 19 women who had healthy fetuses (control
      group) were enrolled in the study. Amniotic fluid was obtained by amniocentesis.
      The chromosomal analysis of the study and control groups was normal. Levels of
      free amino acids were measured in amniotic fluid samples using EZ: fast kits (EZ:
      fast GC/FID free (physiological) amino acid kit) by gas chromatography (Focus GC
      Al 3000 Thermo Finnigan analyzer). The mean levels of alanine, cysteine, glycine
      and valine amino acids were found to be significantly higher in fetuses with non
      immune hydrops fetalis than in the control group (p<0.05). The detection of
      significantly higher amino acid concentrations in the amniotic fluid of fetuses
      with a non immune hydrops fetalis in healthy fetuses suggests loss of amino acids
      from the fetus through capillary permeability or/and the lymphatic system through
      the amniotic fluid may contribute to the etiology of non-immune hydrops fetalis.

PMID- 23157040
TI  - Screening of cervical cancer: 27 years experience in six Republics of Panama.
AB  - Between the years of 1983 and 2010, a program of screening of patients was
      conducted in six of the Republics of Panama, applying cytology, colposcopy, and
      directed biopsy when required. In the community of Pocri de Los Santos, a tour of
      33 rural areas was included in 27 years of consecutive coverage. This allowed to
      confirm that application that screening was successful, resulting in initial,
      evolutionary, or final diagnoses. These were of extreme importance because they
      indicated the disease and its response to conservative treatments applied and to
      the fact that the cancer evolution was nil.

PMID- 23157041
TI  - Female genital mutilation in Greece.
AB  - The number of migrants and refugees with a female genital mutilation (FGM) living
      in Greece is rising. This study explores the characteristics and psychosexual
      issues of women with FGM who were examined in the 2nd Department of Obstetrics
      and Gynecology, University of Athens Medical School, Greece during the year 2009.
      The women were asked to fill out an anonymous questionnaire asking for
      demographic data, obstetric history, current complaints, and psychosexual
      problems. The results are presented and discussed, as FGM is a new reality for
      Greece. Healthcare providers have to familiarize themselves with issues related
      to FGM and improve their skills in transcultural care, so as to manage and
      support women with FGM adequately.

PMID- 23157042
TI  - The effect of sorafenib in postoperative adhesion formation in a rat uterine horn
      model.
AB  - OBJECTIVE: Postoperative adhesions are a serious problem. In this study, we aimed
      to observe the effects of sorafenib in postoperative adhesions and, to examine
      the effects of sorafenib on tissue levels of vascular endothelial growth factor
      (VEGF) and platelet-derived growth factor (PDGF). MATERIAL AND METHODS: Twenty
      female Wistar albino rats were randomized into two equal groups; sorafenib group
      (sorafenib treated) and control group; then all rats underwent laparotomy.
      Adhesions were developed by scalping on the anti-mesenteric surfaces of the right
      uterine horns. After 14 days, adhesions were investigated by using macroscopic,
      histopathological and immunohistochemical (for VEGF and PDGF) methods. RESULTS:
      The sorafenib group had lower scores of total adhesions [1 (0-2.5) vs 1.5 (1-4);
      p: 0.037], staining of VEGF [1 (0-1) vs 1 (1-3); p: 0.029] and PDGF [1 (0-2) vs 2
      (1-3); p: 0.006], and vascular proliferation [1 (0-2) vs 2 (1-3); p: 0.038] than
      the control group. CONCLUSION: The findings of the present study show that
      sorafenib, a tyrosine kinase inhibitor, significantly reduced postoperative
      adhesion formation. This effect may be explained by inhibition of VEGF, PDGF, and
      thus vascular proliferation.

PMID- 23157043
TI  - The efficacy of dinoprostone vaginal insert for active management of premature
      rupture of membranes at term: a randomized controlled trial.
AB  - PURPOSE: To evaluate the efficacy and safety of the vaginal insertion of
      dinoprostone in terms of achieving cervical ripening, shortening the length of
      labor, and lowering the cesarean delivery rate for term pregnancies complicated
      with premature rupture of membranes. METHODS: A prospective, randomized,
      controlled trial enrolled 100 women with term pregnancies complicated with
      premature rupture of membranes. Each had a normal non stress test, unscarred
      uterus, a singleton pregnancy with cephalic presentation, and a Bishop score of
      less than 4. Patients were randomized to receive a 10 mg dinoprostone vaginal
      insert single dose or no medication. After cervical ripening, oxytocin induction
      was performed during labor for both the study and control group. Cervical
      ripening in the 12th hour, total delivery time and delivery mode were compared
      between the two groups. RESULTS: More often cervical ripening was obtained in the
      study group women who used dinoprostone vaginal inserts compared to the control
      group (p: 0.001). Latent phase of labor and total delivery time was shorter in
      the study group women than the control group (p: 0.022 and p: 0.026). There was
      no difference in terms of delivery mode and indication of section between study
      and control groups. CONCLUSION: The use of dinoprostone vaginal inserts in
      patients with term pregnancy of premature rupture of membranes reduced both the
      latent phase of labor and total delivery time without increasing the rate of
      cesarean section.

PMID- 23157044
TI  - Impact of Factor V Leiden, prothrombin and methylenetetrahydrofolate reductase
      gene mutations on infant birth weight in women with recurrent fetal loss and
      women with successful pregnancies.
AB  - PURPOSE: The aim of this study was to verify whether FV Leiden, PT G20210A, MTHFR
      C667T or MTHFR A1298C mutations influence the risk of recurrent fetal loss in a
      sample of Turkish women who had experienced recurrent fetal loss and to evaluate
      whether the aforementioned thrombophilias and recurrent fetal loss may affect the
      birth weight of subsequent pregnancies. METHODS: Fifty-eight women with recurrent
      pregnancy loss and 30 women with successful pregnancies were evaluated. RESULTS:
      The average birth weights for infants of all women in the study group and for
      infants of thrombophilia-positive women in the study group were markedly lower
      than the birth weight of infants in the control group (p<0.001 and p<0.001,
      respectively). CONCLUSION: Successful pregnancies in women with a history of
      recurrent fetal losses may be associated with lower birth weights compared to
      controls, irrespective of thrombophilia status. This conclusion warrants further
      research.

PMID- 23157045
TI  - Effects of tamoxifen and raloxifene on body and uterine weights of rats in
      persistent estrus.
AB  - PURPOSE: To evaluate the change in body and uterine weights of rats in persistent
      estrus, a model developed to mimic polycystic ovary syndrome treated with
      selective estrogen receptor modulators (SERMs) tamoxifen and raloxifene. METHODS:
      Sixty Wistar-Hannover rats induced by a single subcutaneous dose of 1.25 mg
      testosterone propionate were divided into three groups of 20 animals: Group I
      (placebo); Group II (tamoxifen, 250 microg/day) and Group III (raloxifene, 750
      microg/day). At 90 days of life, the treatment began for 30 consecutive days, in
      which the animals were weighed weekly. On the 31st day, the animals were
      sacrificed and the uterus removed. Data were analyzed statistically by analysis
      of variance and by the Tukey-Kramer multiple comparisons test (p<0.05). RESULTS:
      Means of body and uterine weights (g) after treatment were: 227.3+/-2.20 and
      0.40+/-0.01; 185.3+/-2.45 and 0.25+/-0.01; 186.4+/-2.20 and 0.27+/-0.01 in Groups
      I, II and III, respectively (p<0.001). There was no statistical difference
      between groups II and III for body and uterine weight (p=0.727 and p=0.646,
      respectively). CONCLUSION: The present results indicate that, at the doses and
      during the time of treatment used, both tamoxifen and raloxifene reduce in a
      similar way the body and uterine weights of rats in persistent estrus showing a
      possible antiestrogenic effect of SERMs under high levels of estrogens.

PMID- 23157046
TI  - Diagnosis and management of cesarean scar pregnancy.
AB  - OBJECTIVE: To evaluate the diagnosis and management modalities of cesarean scar
      pregnancy according to our experience. DESIGN AND SETTING: Retrospective study at
      the Women's Health Research and Education Hospital. PATIENTS: Six patients were
      diagnosed and treated for cesarean scar pregnancy (CSP) with dilatation and
      curettage, methotrexate (MTX), or laparatomy. RESULTS: One patient chose the
      surgical option due to her desire to have a tubal ligation. In the second case
      methotrexate was applied initially, but two weeks later suction curretage was
      applied due to abdominal pain and vaginal bleeding. Suction curettage was used as
      an initial treatment for four patients. There were not any complications in three
      of four patients. One patient had heavy vaginal bleeding which started after
      curettage. On ultrasonographic examination, increasing hemorrhage was seen
      between the uterus and the bladder so subtotal hysterectomy was performed.
      DISCUSSION: Ultrasound should be used effectivelly in evaluation of pregnant
      patients with previous cesarean deliveries. There is still no unique treatment
      modality for CSP, so treatment should be tailored for each patient. Before the
      7th week, abortion should be considered. After the 7th week, MTX and/or surgical
      options should be preferred.

PMID- 23157047
TI  - Autopsy findings in fetuses with cystic hygroma: a literature review and our
      center's experience.
AB  - PURPOSE OF INVESTIGATION: To report our experience of autopsied cases of fetal
      cystic hygroma (CH) and discuss the role of fetal autopsy in genetic counseling.
      METHODS: A review of autopsy reports at our institution revealed 18 cases of
      fetal CH over a 10-year period (from 2000 to 2010). The clinical data, results of
      cytogenetic analysis and prenatal ultrasound findings were also retrieved and
      compared to the autopsy findings. RESULTS: Fetal death was due to intrauterine
      death in eight cases, therapeutic abortion in eight cases and spontaneous
      abortion in two cases. Cytogenetic analysis was available in 12 cases, and the
      results showed an abnormal karyotype in seven cases (5 cases of Turner syndrome
      and 2 cases of trisomy 21). The mean size of CH was 5.4 cm. Other malformations
      or findings suggestive of the cause of fetal death were diagnosed in 10/18 cases
      (55.6%). The most common autopsy findings were hydrops and central nervous system
      anomalies. The autopsy findings were in agreement with the prenatal ultrasound
      findings in 13/18 cases (72.2%), while in five cases (27.8%) additional findings
      were detected during autopsy. The most common placental abnormalities were
      infarcts and calcifications. CONCLUSION: In addition to prenatal diagnostic
      studies, fetal autopsy and pathologic examination of fetal and placental tissues
      may help to establish the exact cause of death and disclose important information
      as to the presence of various fetal malformations or placental abnormalities.

PMID- 23157048
TI  - The role of amino acids in spina bifida.
AB  - Our objective was to measure amniotic fluid amino acid concentrations in pregnant
      women diagnosed as having fetuses with spina bifida in the second trimester of
      pregnancy. Fifteen pregnant women who had fetuses with spina bifida detected by
      ultrasonography (spina bifida group) in the second trimester and 19 women who had
      abnormal triple screenings indicating an increased risk for Down's syndrome but
      had healthy fetuses (control group) were enrolled in the study. Amniotic fluid
      was obtained by amniocentesis. The chromosomal analysis of the study and control
      groups was normal. Levels of free amino acids were measured in amniotic fluid
      samples using EZ: fast kits (EZ: fast GC/FID free (physiological) amino acid kit)
      by gas chromatography (Focus GC AI 3000 Thermo Finnigan analyzer). The mean
      levels of alanine, cystathionine, cysteine, phenylalanine, tryptophane, and
      tyrosine amino acids were found to be significantly higher in fetuses of the
      control group than in the spina bifida group (p<0.05). The detection of
      significantly higher amino acid concentrations in the amniotic fluid of healthy
      fetuses suggests loss of amino acids from the fetus through the spinal cord may
      contribute to the etiology of spina bifida.

PMID- 23157049
TI  - Secondary missed abdominal pregnancy due to iatrogenic uterine perforation: a
      case report.
AB  - Abdominal pregnancy is extremely rare and can result from the reimplantation of
      an intrauterine pregnancy after spontaneous uterine rupture. In this report, we
      present the case of a secondary missed abdominal pregnancy resulting from
      iatrogenic uterine perforation during dilatation and curettage in an early
      intrauterine pregnancy and subsequently misdiagnosed as intrauterine
      trophoblastic disease. Transvaginal ultrasound missed the diagnosis, which was
      finally confirmed by computed tomography. We discuss the particulars of the case
      along with a review of the relevant literature.

PMID- 23157050
TI  - Peritoneal enterobiasis causing endometriosis-like symptoms.
AB  - PURPOSE: Enterobiasis is the most common parasitic disease of the temperate zones
      and infects the human intestinal tract. In rare cases extraintestinal infections
      with Enterobius vermicularis may occur and can affect the female genital tract
      and peritoneal cavity. In most cases the infection is asymptomatic, but there are
      also cases described in which peritoneal enterobiasis can cause abdominal pain.
      METHODS: A case report and review of the pertinent literature. RESULTS: A 32-year
      old patient was admitted with cyclical lower abdominal pain. With suspected
      endometriosis a diagnostic autofluorescence laparoscopy (DAFE) was performed. At
      surgery extensive peritoneal deposits were seen. Macroscopically these deposits
      were not typical for endometriosis. The histological examination showed granuloma
      caused by E. vermicularis eggs. The patient was treated with mebendazole. After
      completion of treatment the patient was asymptomatic. At the second-look
      laparoscopy no more peritoneal changes were detected. CONCLUSION: Enterobius
      vermicularis may cause symptoms similar to endometriosis. In cases with
      reasonable suspicion it should therefore be considered in the differential
      diagnosis.

PMID- 23157051
TI  - Uncorrected tetralogy of Fallot and pregnancy: a case report.
AB  - We report a case of pregnancy in a 34-year-old woman with uncorrected tetralogy
      of Fallot (TOF). There are more risks in patients without surgical correction. In
      our case, haemoglobin and haematocrit were higher, oxygen saturation was lower,
      and right ventricular enlargement was observed. Pregnancy was resolved
      successfully by caesarean section. Improvement of fetomaternal outcome may be
      related to corrective procedures before conception to achieve better functional
      heart capacity. Delicate multidisciplinary medical management is essential for
      these limited cases to achieve optimal prognosis.

PMID- 23157052
TI  - Mediastinal masses: a case of fetal teratoma and literature review.
AB  - Fetal mediastinal masses are rare congenital formations that could complicate
      pregnancy. They are usually discovered as space occupying lesions in the fetal
      chest during routine ultrasound scan. The most important prognostic factors of
      mediastinal masses are mass location, compressing effect causing pulmonary
      hypoplasia and/or heart failure, and the presence or absence of hydrops. We
      report a case of fetal mediastinal teratoma and a review of the literature. A 32
      year-old woman carrying a fetus with hydrops due to a mediastinal mass underwent
      cesarean section at 32 1/7 weeks' gestation. A well encapsulated tumor was
      excised by surgery at one day of life. The baby is now eight months old without
      respiratory difficulty. To our knowledge, this is the fourth case report of a
      mediastinal teratoma associated with nonimmune hydrops in a fetus that survived
      the neonatal period. Fetal mediastinal teratoma requires close surveillance and
      multidisciplinary management by obstetricians, neonatologists, and pediatric
      surgeons.

PMID- 23157053
TI  - Tubo-ovarian abscess presenting as an ovarian tumor in a virginal adolescent: a
      case report.
AB  - Tubo-ovarian abscess (TOA), a serious complication of pelvic inflammatory
      disease, unites the fallopian tube and ovary and, is rarely observed in sexually
      inactive adolescent girls. A pelvic mass, supposedly originating from the ovary,
      was detected in a 13-year-old sexually inactive girl suffering from abdominal
      pain and menstrual disorder. Pelvic ultrasonography pointed out a semisolid,
      hyperechogenic mass of 57x73 mm in the left adnexal area. Laparotomy revealed an
      unilateral TOA adhering to the bowel and omentum. Abscess drainage and
      adhesiolysis were performed and postoperative antibiotherapy was administered.
      TOA should be considered in the differential diagnosis of females with abdominal
      pain and adnexal mass whether sexual activity is present or not.

PMID- 23157054
TI  - Early ovarian pregnancy diagnosed by ultrasound and successfully treated with
      multidose methotrexate. A case report.
AB  - A case report of a primary interstitial ovarian pregnancy is presented. A 37-year
      old married woman with two children after two Cesarean sections and a spontaneous
      abortion, with a contraceptive intrauterine device (IUD) inserted three years
      before, presented at five weeks plus five days amenorrhea with a positive
      pregnancy test and lower abdominal pain but with no vaginal bleeding. Her
      previous menstrual cycles had been regular. She was hemodynamically stable. On
      bimanual examination, the uterus was of normal size, and there was an approximate
      four-cm tender right adnexal mass. Serum beta-human chorionic gonadotropin (b
      hCG) was confirmed positive. Ultrasound revealed a well-positioned IUD in the
      uterus and a right adnexal mass with normal vascular flow on Doppler, that
      contained a well-defined gestational sac, well-distinct from the quiescent
      hemorrhagic corpus luteum. There was no fetal node or cardiac activity or free
      fluid. The patient received four injections of methotrexate intramuscularly using
      the multidose regimen that involves the administration of methotrexate calculated
      according to body weight, alternated with 0.1 mg/kg of leucovorin calcium per os
      after 30 hours until the values of 3-hCG had decreased by 15%. The patient's post
      treatment period was uneventful with a full restoration of ovarian morphology and
      the complete absorption of the gestational sac. This case is the first where
      diagnosis was made by endovaginal sonography and treatment was made by multidose
      methotrexate. Spiegelberg criteria for the diagnosis of ovarian pregnancy are
      obsolete; new ultrasound and laboratory criteria are needed for a diagnosis as
      early as possible without the need of surgery.

PMID- 23157055
TI  - Silent rupture of an unscarred uterus at third-trimester abortion correlated with
      an unrecognized perforation.
AB  - Silent uterine rupture in an unscarred uterus during pregnancy is rare. We
      present a case of silent uterine rupture in an unscarred uterus at third
      trimester abortion by use of mifepristone and misoprostol in a patient who had a
      history of intrauterine procedures. The absence of clinical symptoms suggests
      that this uterine rupture resulted from an unrecognized perforation in a previous
      intrauterine manipulation. Routine sonographic follow-up examinations and careful
      clinical observations are especially recommended for women with previous
      intrauterine manipulations.

PMID- 23157056
TI  - Treatment of early heterotopic interstitial (cornual) gestation with subsequent
      delivery of an intrauterine pregnancy--case report.
AB  - We present the case of a 38-year-old woman who was treated for a heterotopic
      interstitial (cornual) pregnancy diagnosed at the 7th week of gestation. The
      intervention was performed via transvaginal ultrasound-guided aspiration and
      instillation of a hypertonic solution of sodium chloride into the cornual sac.
      The heterotopic comrnual pregnancy was successfully aborted, and the intrauterine
      pregnancy was successfully maintained with delivery of a healthy newborn.

PMID- 23157057
TI  - Obstetric rupture of the rectovaginal septum and sphincter complex despite an
      intact perineum: report of three cases.
AB  - Obstetric injury comprising tearing of the rectovaginal septum, rectal mucosa,
      and anal sphincter complex with limited or no involvement of the perineal body
      may implicate the sudden appearance of an elbow, foot or head in the anal orifice
      during the second phase of labour. This complex type of obstetric injury is
      highly uncommon and reports have rarely been published. There are no guideliness
      as to how to respond to this obstetric emergency and there is no time for
      consultation. In order to reach clinical recommendations on repair and management
      of this unexpected obstetric injury for the midwife or obstetrician, we report
      three such cases. The three described cases with their corresponding sequence of
      events and interventions illustrate that successful repair of these types of
      injury can often be achieved. To minimize factors leading to long-term
      complications, repair requires the involvement of an experienced gynaecologist
      and sometimes even a colorectal surgeon.

PMID- 23157058
TI  - Quadruplet pregnancy complicated by ovarian hyperstimulation syndrome with
      spontaneous ovulation.
AB  - Ovarian hyperstimulation syndrome (OHSS) commonly occurs as a complication of
      ovarian stimulation with gonadotrophins. Spontaneous OHSS is an extremely rare
      event, but can occur as a result of stimulation with pregnancy-derived hCG. We
      herein report a case of quadruplet pregnancy complicated by OHSS with spontaneous
      ovulation. The patient had previously undergone ovarian stimulation with
      clomiphene citrate plus FSH. After that, she conceived spontaneously and
      developed OHSS after three weeks of amenorrhea. The OHSS was managed by
      conservative treatment and improved at six weeks of gestation. However, a
      quadruplet pregnancy became apparent on ultrasound examination. The patient
      therefore elected to have an induced abortion. Besides the conception in the
      cycle without administration of exogenous gonadotrophins, the symptoms in this
      case had the same kinetics as iatrogenic OHSS caused by ovarian stimulation.

PMID- 23157059
TI  - Missing ductus venosus: a case report.
AB  - BACKGROUND: The ductus venosus is a short vessel, present in the newborn infant
      on the dorsal surface of the liver, connecting the portal and umbilical
      circulation with the inferior vena cava. Agenesis of the duct is a rare anomaly.
      CASE: A 28-year-old woman was referred to our department for the first trimester
      ultrasound evaluation. Detailed scanning revealed agenesis of the duct. Fetal
      echocardiography showed cardiac disproportion at the level of the ventricles.
      CONCLUSION: Agenesis of the duct can be related to either cardiac or congenital
      abnormalities.

PMID- 23157060
TI  - Spontaneous rupture of splenic hemangioma in puerperium.
AB  - Atraumatic splenic rupture is a rare clinical entity and in the absence of
      trauma, the diagnosis and treatment are often delayed. In this article the
      authors discuss a case of a 45-year-old woman, gravida 5, para 4, with
      spontaneous splenic rupture on her second postpartum day. The rupture was related
      to a splenic hemangioma that is a vascular malformation and the most common
      neoplasm of the spleen. Despite the fact that hemangiomas are the most common
      primary neoplasms of the spleen, only few cases of splenic rupture have been
      described in pregnancy or puerperium. However, spontaneous splenic rupture is a
      rare event and the rupture should be suspected in woman with unexplained
      abdominal pain or with clear signs of haemorrhage.

PMID- 23157061
TI  - Adenomyosis completely encapsulated by muscle-like cavity in the mesorectum: a
      case report.
AB  - A case of adenomyosis, completely encapsulated and located in the mesentery
      between the sigmoid colon and rectum, was admitted our hospital. We have reported
      the symptoms, diagnosis, and treatment of the present case.

PMID- 23157062
TI  - The challenging trisomy 16: a case report.
AB  - BACKGROUND: Trisomy 16 is a very frequent autosomal anomaly accounting for about
      2% of first trimester abortions. In most pregnancies the chromosomal genome found
      in the fetus is also present in the placenta. Confined placental mosaicism is
      frequently detected in the placental region along with a structurally normal
      fetus. CASE: We present the case of a 39-year-old primigravida with confined
      placental mosaicism diagnosed with chorionic villus sampling. Amniocentesis
      showed a normal karyotype (46, XX). Detailed scanning revealed no structural
      fetal anomalies, but severe oligohydramnios. CONCLUSION: Diagnosis of trisomy 16
      does not necessarily mean that the newborn has anatomical abnormalities.

PMID- 23157063
TI  - Acute generalized exanthematous pustulosis during the puerperal period: a case
      report.
AB  - BACKGROUND: Acute generalized exanthematous pustulosis (AGEP) is an uncommon
      adverse cutaneous reaction, most commonly associated with drugs. CASE: A 38-year
      old primigravida whose labor had been induced developed erythema over her chest
      and abdomen. She was transferred to our department after a failed vacuum
      extraction, and delivered a mature infant by forceps. On day three postpartum she
      developed a 40.4 degrees C fever. Although ceftriaxone was administered, her
      fever persisted (>38 degreesC). On day six of the puerperium, diffuse non
      follicular pustules appeared over her neck and trunk, and AGEP was suspected. Two
      days after ceftriaxone was withdrawn, the eruptions started to resolve without
      any medical intervention. CONCLUSION: Once the diagnosis of AGEP has been made,
      the antibiotics being administered must be discontinued. If continued treatment
      is required, pharmacologically distinct antibiotics must be used instead to aid
      the rapid self-limitation of the disease.

PMID- 23157064
TI  - [Cuts, indignation, and scientific and professional development].

PMID- 23157065
TI  - [Clinical cases about the therapeutic use of debriding dressing hidrodetersive
      polyacrylate fibers with TLC and foam dressings TLC-NOSF polyurethane in chronic
      wounds].
AB  - The treatment of chronic wounds requires the use of highly specific products for
      different phases of the healing process. This article raises a number of clinical
      cases with chronic wounds of vascular origin and pressure ulcers. Such cases
      required a initial debridement because of the large content of fibrin covering
      the wound bed at this stage was used dressing hidrodetersive polyacrylate fibers
      with TLC. Once the debridement is continued treatment with a polyurethane foam
      dressing with TLC-NOSF.

PMID- 23157066
TI  - [Burnout syndrome of health workers in an assisted residence for the elderly].
AB  - OBJECTIVES: to estimate the prevalence of Burnout Syndrome and the sleep patterns
      alterations experienced by health workers who work in an Assisted Residence for
      the Elderly. MATERIAL AND METHODS: descriptive and cross-sectional research using
      the Maslach Burnout Inventory and the Sleepiness Epworth scales in a self
      questionnaire that was aimed to 150 employees at the institution. We used
      descriptive and inferential statistics with a 95% confidence interval. The
      relationship between categorical variables was carried out using the non
      parametric Mann-Whitney test. RESULTS AND CONCLUSIONS: response rate of 92% (138)
      on the total respondents (150). The burnout prevalence rate is located at 21.7%
      with a high percentage of workers with low personal fulfillment (64.1%). There is
      also a slight tendency to suffer from daytime sleepiness in general. It is worth
      highlighting musculoskeletal problems as the main physiological conditions in
      relation to the type of work (70.3%), being coffee as the most consumed substance
      of those polled. High level prevalence of burnout syndrome in the population
      studied, especially among the nursing staff and the need to develop interventions
      to reduce them.

PMID- 23157067
TI  - [How to prepare the back home with baby in the maternal education programs in
      Madrid].
AB  - JUSTIFICATION: To improve maternal and child health is important to work the
      postpartum familiar reorganization in the maternal education programs.
      OBJECTIVES: To know the scientific evidence of the postnatal care. To look for a
      framework for nursing. To explore the educative strategies that midwives use in
      maternal education in Madrid (Spain). METHODS: Review of the evidence of prenatal
      and postnatal cares. Review of nursing models. Qualitative study. Probabilistic
      sample about 42 midwives of Primary Attention in Madrid that delivered programs
      of Maternal Education in 2011. Deep interviews. Interviews were coded and
      classified according to the method ofe based theory) through constant comparative
      analysis. Ethic and legal considerations. RESULTS: 14 clinic guides, 10 revisions
      and thousand of articles about postpartum care found. A theory of middle range
      found that allows to base nursing work in the familiar reorganization. 100% of
      midwives approached the topic and considered it very important. 36% of midwives
      worked with a case; 27% invited parents to a class; 14% showed the topic to
      pregnant woman; 11% used group dynamics; 7% through colloquium and 5% used cinema
      material. They did not use conceptual frameworks, neither specific evaluations,
      nor homework. CONCLUSION: Data allow us to know the scientific evidence, the
      approach that is performed in maternal education and new investigation proposals
      to offer care of high quality.

PMID- 23157068
TI  - [Physical methods used to control body temperature].
AB  - The physical methods to control body temperature, either to induce hypothermia,
      or to increase body temperature, can be of two types: physical methods of
      external heating or cooling and invasive methods that require complex procedures
      and technology. There are many strategies for the induction of hypothermia, all
      based on three of the four basic mechanisms of heat transfer, evaporation,
      convection and conduction. In the hospital environment the external cooling
      methods or surface (blankets of cold air or water circulation, plates of hydrogel
      Artic Sun, methods of cooling helmet) are the most widely used for the induction
      of therapeutic hypothermia. The most non-invasive devices used are blades of
      hydrogel, which use water conduction high speed between the layers of pads. But
      there are quicker methods to induce hypothermia; i.e., invasive methods of
      internal cooling: infusion of intravenous crystalloid; endovascular catheters
      located in a central vein through which flows saline pumped by a closed circuit;
      By-pass cardio-pulmonary with extracorporeal circulation; and By-pass
      percutaneous venous system for continuous hemofiltration. The average physical
      external heating is based on the patient's ability to produce and retain heat or
      in the application of heat to the body surface of the patient (hot spring baths
      with hot water, air blankets, blankets of water). But when the answer to these
      methods are not sufficient or hypothermia is moderate or severe, other methods of
      internal heat are suggested: inhalation of oxygen or warm to 40-45 degrees C and
      wet by facial mask or endotracheal tube; intravenous (IV) infusion with hot
      solutions; Irrigation of body cavities with warm saline solution to 40-42 degrees
      C; peritoneal dialysis, haemodialysis and hemofiltration; Continuous reheating
      arterio-venous or venous-venous; extracorporeal circulation with cardiopulmonary
      bypass. In this article each of the methods listed above will be described for
      the induction of hypothermia and overheating.

PMID- 23157069
TI  - [Therapeutic education didactic techniques].
AB  - This article includes an introduction to the role of Therapeutic Education for
      Diabetes treatment according to the recommendations of the American Diabetes
      Association (ADA), the Diabetes Education Study Group (DESG) of the "European
      Association for Study of Diabetes (EASD) and the clinical Practice Guidelines
      (CPG) of the Spanish Ministry of Health. We analyze theoretical models and the
      differences between teaching vs. learning as well as current trends (including
      Internet), that can facilitate meaningful learning of people with diabetes and
      their families and relatives. We analyze the differences, similarities,
      advantages and disadvantages of individual and group education. Finally, we
      describe different educational techniques (metaplan, case method, brainstorming,
      role playing, games, seminars, autobiography, forums, chats,..) applicable to
      individual, group or virtual education and its application depending on the
      learning objective.

PMID- 23157070
TI  - [Death anxiety in nursing: experience in supporting of the death and field care].
AB  - OBJECTIVE: The aim of this research is to determine the relationship between
      professional experience in palliative care, and the assistance area in which that
      palliative care occurs, and the degree of anxiety before the death in
      professional nursing. We also explored the relationships between demographic and
      work variables with death anxiety, replicating existing studies. METHOD: Is a
      quantitative and descriptive and comparative study in 2009 in La Xarxa Sanitaria
      Santa Tecla in Tarragona. The study's sample population was nurses of different
      levels of assistance (n=105) who answered the selected means for the collection
      of socio-demographic variables and the measurement of the degree of death anxiety
      (Spanish version of CL-FODS). RESULTS: We found significant statistic difference
      on the points of scale anxiety in the presence of the death with the nurses
      belonging to several assistance areas. The care frequency to moribund people is
      shown definitely of fear levels to the proper death as well as the assiduity in
      which professionals talk about death in private surroundings. CONCLUSIONS: The
      assistance area as scene of care moments to moribund people which theses
      professionals share, and the frequency of the fulfilment of theses cares
      constitute definite elements to their fear or anxiety to the death.

PMID- 23157072
TI  - [Our challenge: to recover hope].

PMID- 23157071
TI  - [Influence of emotions in affective-sexual relations].
AB  - The aim of this article is to publicize the influence that can have emotions in
      sexual and affective relations of patients. It arises basically from the clinical
      observation of patients in the field of the couples and sex therapy therapy.

PMID- 23157073
TI  - [XVI International Meeting on Care Research INVESTEN-ISCIII].

PMID- 23157074
TI  - [We always learn from civilian nurses].

PMID- 23157075
TI  - Heterogeneous modeling of medical image data using B-spline functions.
AB  - Biomedical data visualization and modeling rely predominately on manual
      processing and utilization of voxel- and facet-based homogeneous models.
      Biological structures are naturally heterogeneous and it is important to
      incorporate properties, such as material composition, size and shape, into the
      modeling process. A method to approximate image density data with a continuous B
      spline surface is presented. The proposed approach generates a density point
      cloud, based on medical image data to reproduce heterogeneity across the image,
      through point densities. The density point cloud is ordered and approximated with
      a set of B-spline curves. A B-spline surface is lofted through the cross
      sectional B-spline curves preserving the heterogeneity of the point cloud
      dataset. Preliminary results indicate that the proposed methodology produces a
      mathematical representation capable of capturing and preserving density
      variations with high fidelity.

PMID- 23157076
TI  - Limited benefit of hamstrings forces for the anterior cruciate ligament-deficient
      knee: an in vitro study.
AB  - The hamstrings are considered stabilizers of the anterior cruciate ligament
      deficient knee; however, anterior cruciate ligament injury primarily influences
      tibiofemoral kinematics near full extension, where the hamstrings have the least
      influence on kinematics. Ten knees were tested at multiple flexion angles in
      vitro to directly compare the influence of anterior cruciate ligament injury and
      hamstrings activation on tibiofemoral kinematics. Tibiofemoral kinematics were
      measured for three testing conditions: (1) anterior cruciate ligament intact,
      with forces applied through the quadriceps muscles (596 N), (2) anterior cruciate
      ligament cut, with forces applied through the quadriceps, and (3) anterior
      cruciate ligament cut, with forces applied through the quadriceps and hamstrings
      (200 N). Based on repeated measures comparisons performed at each flexion angle,
      cutting the anterior cruciate ligament significantly (p < 0.05) increased tibial
      anterior translation, medial translation, and internal rotation at 0 degrees and
      15 degrees of flexion by approximately 2.5 mm, 1 mm, and 2 degrees, respectively.
      Internal rotation also increased significantly at 30 degrees. With the anterior
      cruciate ligament cut, loading the hamstrings significantly decreased anterior
      translation, medial translation, and internal rotation at 45 degrees, by
      approximately 2 mm, 2 mm, and 4 degrees, respectively. Loading the hamstrings
      caused kinematic changes in the opposite direction of the anterior cruciate
      ligament injury, but the changes occurred at deeper flexion angles than those at
      which anterior cruciate ligament injury influenced tibiofemoral kinematics.

PMID- 23157077
TI  - Useful method to monitor the physiological effects of alcohol ingestion by
      combination of micro-integrated laser Doppler blood flow meter and arm-raising
      test.
AB  - Alcohol has a variety of effects on the human body, affecting both the
      sympathetic and parasympathetic nervous system. We examined the peripheral blood
      flow of alcohol drinkers using a micro-integrated laser Doppler blood flow meter
      (micro-electromechanical system blood flow sensor). An increased heart rate and
      blood flow was recorded at the earlobe after alcohol ingestion, and we observed
      strong correlation between blood flow, heart rate, and breath alcohol content in
      light drinkers; but not heavy drinkers. We also found that the amplitude of pulse
      waves measured at the fingertip during an arm-raising test significantly
      decreased on alcohol consumption, regardless of the individual's alcohol
      tolerance. Our micro-electromechanical system blood flow sensor successfully
      detected various physiological changes in peripheral blood circulation induced by
      alcohol consumption.

PMID- 23157078
TI  - Improvement in the clinical practicability of roentgen stereophotogrammetric
      analysis (RSA): free from the use of the dual X-ray equipment.
AB  - After total knee replacement, the monitoring of the prosthetic performance is
      often done by roentgenographic examination. However, the two-dimensional (2D)
      roentgen images only provide information about the projection onto the
      anteroposterior (AP) and mediolateral (ML) planes. Historically, the model-based
      roentgen stereophotogrammetric analysis (RSA) technique has been developed to
      predict the spatial relationship between prostheses by iteratively comparing the
      projective data for the prosthetic models and the roentgen images. During
      examination, the prosthetic poses should be stationary. This should be ensured,
      either by the use of dual synchronized X-ray equipment or by the use of a
      specific posture. In practice, these methods are uncommon or technically
      inconvenient during follow-up examination. This study aims to develop a rotation
      platform to improve the clinical applicability of the model-based RSA technique.
      The rotation platform allows the patient to assume a weight-bearing posture,
      while being steadily rotated so that both AP and ML knee images can be obtained.
      This study uses X-ray equipment with a single source and flat panel detectors
      (FPDs). Four tests are conducted to evaluate the quality of the FPD images,
      steadiness of the rotation platform, and accuracy of the RSA results. The results
      show that the distortion-induced error of the FPD image is quite minor, and the
      prosthetic size can be cautiously calibrated by means of the scale ball(s). The
      rotation platform should be placed closer to the FPD and orthogonal to the
      projection axis of the X-ray source. Image overlap of the prostheses can be
      avoided by adjusting both X-ray source and knee posture. The device-induced
      problems associated with the rotation platform include the steadiness of the
      platform operation and the balance of the rotated subject. Sawbone tests
      demonstrate that the outline error, due to the platform, is of the order of the
      image resolution (= 0.145 mm). In conclusion, the rotation platform with steady
      rotation, a knee support, and a handle can serve as an alternative method to take
      prosthetic images, without the loss in accuracy associated with the RSA method.

PMID- 23157079
TI  - Biomechanical influence of pin placement and elbow angle on joint distraction and
      hinge alignment for an arthrodiatasis elbow-pin-fixator construct.
AB  - Stiffness and contracture of the periarticular tissues are common complications
      of a post-traumatic elbow. Arthrodiatasis is a surgical technique that uses an
      external fixator for initial immobilization and subsequent distraction. The two
      prerequisites for an ideal arthrodiatasis are concentric distraction (avoiding
      bony contact) and hinge alignment (reducing internal stress). This study used the
      finite element (FE) method to clarify the relationship between these two
      prerequisites and the initial conditions (pin placement, elbow angle, and
      distraction mode). A total of 12 variations of the initial conditions were
      symmetrically arranged to evaluate their biomechanical influence on concentric
      distraction and hinge alignment. The humeroulnar surface was hypothesized to be
      ideally distracted orthogonal to the line joining the tips of the olecranon and
      the coronoid. The eccentric separation of the humeroulnar surfaces is a response
      to the non-orthogonality of the distracting force and joining line. Pin placement
      significantly affects the effective moment arm of the fixing pins to distract the
      bridged elbow. Both elbow angle and distraction mode directly alter the direction
      of the distracting force at the elbow center. In general, the hinges misalignment
      occurs in a direction opposite to the distraction-activated site. After joint
      distraction, the elastic deflection of the fixing pins inevitably makes both
      elbow and fixator hinges to misalign. This indicates that both joint distraction
      and hinge alignment are the interactive mechanisms. The humeroulnar separation is
      more concentric in the situation of the 120 degrees humeral distraction by using
      stiffer pins with convergent placement. Even so, the eccentric displacement of
      the elbow hinge is a crucial consideration in the initial placement of the
      guiding pin to compensate for hinge misalignment.

PMID- 23157080
TI  - Development of a cardiopulmonary mathematical model incorporating a baro
      chemoreceptor reflex control system.
AB  - This article describes the development of a comprehensive mathematical model of
      the human cardiopulmonary system that combines the respiratory and cardiovascular
      systems and their associated autonomous nervous control actions. The model is
      structured to allow the complex interactions between the two systems and the
      responses of the combined system to be predicted under different physiological
      conditions. The cardiovascular system model contains 13 compartments, including
      the heart chambers operating as a pump and the blood vessels represented as
      distensible tubes configured in a serial and parallel arrangement. The accurate
      representation of the hemodynamics in the system and the good fit to published
      pressure and flow waveforms gave confidence in the modelling approach adopted for
      the cardiovascular system prior to the incorporation of the baroreflex control
      and the respiratory models. An improved baroreceptor reflex model is developed in
      this research, incorporating afferent, central and efferent compartments. A
      sigmoid function is included in the efferent compartment to produce sympathetic
      and parasympathetic nerve outflow to the effector sites. The baroreflex action is
      modelled using physiological data, its interaction with the chemoreflex control
      is explained and the simulation results presented show the ability of the model
      to predict the static and dynamic hemodynamic responses to environmental
      disturbances. A previously published respiratory model that includes the
      mechanics of breathing, gas exchange process and the regulation of the system is
      then combined with the cardiovascular model to form the cardiopulmonary model.
      Through comparison with published data, the cardiopulmonary model with the baro
      chemoreflex control is validated during hypoxia and hypercapnia. The percentage
      difference between the predicted and measured changes in the heart rates and the
      mean arterial pressures are within 3% in both cases. The total peripheral
      resistance correlates well for hypoxia but is less good for hypercapnia, where
      the predicted change from normal condition is around 7% compared with a measured
      change of 23%. An example showing the application of the proposed model in sport
      science is also included.

PMID- 23157081
TI  - Mathematical formulae to calculate the theoretical range of motion of prosthetic
      hip implants with non-circular neck geometry.
AB  - Component design and position are major factors in achieving adequate range of
      motion post hip replacement. It is therefore important to understand how implant
      design and positioning impact the motion available before impingement. The
      Yoshimine-Ginbayashi equations allow the theoretical range of motion of total hip
      replacements to be calculated accurately and quickly. However, a significant
      limitation of these equations is that they can only be applied to femoral neck
      geometry with a circular cross section. The objective of the present study was to
      reformulate the equations to allow fast and accurate calculation of the range of
      motion for prostheses with any femoral neck geometry. Using vector analysis,
      formulae were derived such that the range of motion could be calculated from the
      cross section of the neck at the point of impingement, cup radius at the point of
      impingement, cup inclination angle, cup anteversion angle, neck angle of the
      femoral component from the transverse plane and neck anteversion. The range of
      motion was calculated for circular, truncated circle and free-form femoral neck
      geometry under a range of component positions. These values were successfully
      compared with those measured from analysis of solid models in three-dimensional
      computer-aided design software. The method of analysis presented offers a
      powerful new technique enabling hip prostheses to be analysed in an accurate and
      efficient manner, therefore facilitating optimisation of the design geometry,
      assessment of existing pre-clinical designs and clinical pre- or postoperative
      evaluation.

PMID- 23157082
TI  - [Role of anesthesiologists in the treatment of cancer pain].

PMID- 23157083
TI  - [Local instillation of 0.75% ropivacaine compared with intravenous fentanyl and
      flurbiprofen for postoperative analgesia following inguinal hernia repair in
      adults].
AB  - BACKGROUND: We compared postoperative analgesia provided by local instillation of
      0.75% ropivacaine with that by intravenous fentanyl and flurbiprofen. METHODS:
      Twenty-nine adult patients undergoing an inguinal hernia repair procedure under
      general anesthesia were randomly divided into Groups F and R according to the
      method of postoperative analgesia. Those in Group F were administered fentanyl
      and flurbiprofen, while Group R was given a local instillation of 0.75%
      ropivacaine (20 ml) into the wound. Non-steroidal anti-inflammatory drugs
      (NSAIDs, oral loxoprofen 60 mg or rectum delivery of diclofenac at 25 mg) were
      administered according to patient request after the operation. The Prince Henry
      pain scale, and the use of NSAIDs and complications were also examined. RESULTS:
      There were no significant differences between the groups for demographic data. In
      Group R, the pain score was significantly lower from arrival at the ward to
      bedtime and the frequency of NSAID use was also significantly lower. No
      complications were seen in either group. CONCLUSIONS: Local instillation of 0.75%
      ropivacaine is safe and effective, and provides adequate analgesia for a long
      period in adult patients following an inguinal hernia repair procedure.

PMID- 23157084
TI  - [Comparison of the Supreme Laryngeal Mask Airway(SLMA), single use, with the
      reusable Proseal Laryngeal Mask Airway(PLMA) in anesthetized adult Japanese
      patients].
AB  - BACKGROUND: Supreme laryngeal mask airway (SLMA) is a single use, new
      supraglottic airway device with anatomically designed curved airway conduit. It
      has second channel for gastric tube insertion. We compared the performance of the
      SLMA with that of the Proseal LMA (PLMA), the older reusable LMA, during
      anaesthesia in spontaneously breathing adult patients. METHODS: One hundred adult
      patients were studied in a prospective randomized controlled study. Insertion
      time, first attempt success rates, leak pressure, ease of gastric tube placement,
      and the incidence of blood staining on removal, as well as sore throat and
      hoarseness were compared. For statistical analyses, Student's t test, Mann
      Whitney's U test, and Fisher's exact test were used where appropriate, and P<0.01
      considered significant. RESULTS: SLMA provided faster insertion time (11 vs 18
      seconds, P<0.01). Leak pressure was higher for PLMA (25 vs 28cmH2O, P<0.01).
      First attempt success rates, gastric tube placement and the incidence of
      complications were similar. CONCLUSIONS: Our result indicated that SLMA can be
      inserted faster without inserting one's finger into patient oral cavity. Leak
      pressure was lower but acceptable for clinical use in spontaneously breathing
      anesthetized adult patients.

PMID- 23157085
TI  - [Investigation of preoperative respiratory evaluation in four cases of myasthenia
      gravis undergoing extended thymectomy in the past two years].
AB  - BACKGROUND: Myasthenia gravis (MG) is an autoimmune disease. The MG patients
      undergoing extended thymectomy under general anesthesia are at risk for
      postoperative complications, such as respiratory insufficiency and crisis
      (cholinergic and myasthenic). We evaluated the preoperative predictive factors,
      which are important for postoperative respiratory control. METHODS: Four patients
      undergoing extended thymectomy under general anesthesia in our hospital within
      the last two years (2008-2010) were studied. All patients were graded with
      Ossermann Classification (I, IIa, IIb, IIb), MGFA Clinical Classification (Class
      I, IIIb, IIIb, IIIb) and Fuchu Hospital Scoring System (2, 4, 5, 10). RESULTS:
      One patient was re-intubated in postoperative 5 days due to myasthenic crisis.
      The patient had a high values in Fuchu Hospital Scoring System (10), longer
      duration of myasthenia (84 months) and higher preoperative anti-acetylcholine
      receptor antibody value (1,200 nmol x l(-1)). CONCLUSIONS: This finding suggests
      that Fuchu Hospital Scoring System, duration of myasthenia and preoperative anti
      acetylcholine receptor antibody are valuable for MG patients undergoing extended
      thymectomy as preoperative predictive factors. These factors are important for
      postoperative respiratory control.

PMID- 23157086
TI  - [Investigation of the outcomes and complications in right thoracotomy approach
      for mitral valve reoperation].
AB  - BACKGROUND: Right thoracotomy is an alternative surgical technique for mitral
      valve reoperation. The purpose of this study is to determine whether right
      thoracotomy for mitral valve reoperation affects its perioperative outcomes and
      complications. METHODS: We investigated the perioperative events in consecutive
      mitral valve reoperations between January 2006 and November 2009. Demographic,
      intraoperative and postoperative data were collected and analyzed
      retrospectively. RESULTS: Five right thoracotomy cases and 22 repeated sternotomy
      cases were included. Thoracotomy group needed more platelet transfusion (median,
      20 units in thoracotomy; 10 units in sternotomy; P=0.047). We had a higher
      frequency of adrenaline administration (60% in thoracotomy; 4.6% in sternotomy;
      P=0.005) and needed more doses of dobutamine in thoracotomy group (median, 16.0
      microg x kg(-1) x min(-1) in thoracotomy ; 7.5 microg x kg(-1) x min(-1) in
      sternotomy; P=0.037) to wean them from cardiopulmonary bypass. Right thoracotomy
      did not reduce cardiopulmonary bypass time (median, 265 min in thoracotomy ; 199
      min in sternotomy; P=0.126). We experienced two serious complications requiring
      reoperation in thoracotomy group, but diagnosed them with intraoperative
      transesophageal echocardiography. CONCLUSIONS: When we choose right thoracotomy
      for mitral valve reoperation, we should prepare more blood products and inotropic
      agents and should evaluate cardiac function by using intraoperative
      transesophageal echocardiography.

PMID- 23157087
TI  - [Postoperative pain management by intravenous patient-controlled analgesia in
      patients undergoing upper abdominal gastrointestinal surgery].
AB  - BACKGROUND: We conducted a retrospective study to evaluate the effectiveness of
      intravenous patient-controlled analgesia (IVPCA) in the early postoperative
      period after upper abdominal gastrointestinal surgery. We also evaluated the
      postoperative effects of intraoperative analgesic dosage in patients after this
      surgery. METHODS: A total of 59 adult patients classified as ASA 1-3 were
      allocated to one of two groups: Group A, 23 patients who requested IVPCA more
      than 50 times, and Group B, 36 patients with fewer than 50 requests. IVPCA was
      induced using morphine 1 mg x ml(-1) without a base dose. The bolus dose was 1 ml
      and the lock-out time was 5 min. RESULTS: There was no significant difference
      between the two groups in the total intraoperative remifentanil dosage/body
      weight/surgical duration, predicted effect-site concentration of fentanyl during
      extubation, and utilization of flurbiprofen. The doses of morphine were
      significantly higher, and the visual analogue scale scores for pain at rest and
      during movement tended to be lower in group A than in group B. CONCLUSIONS: The
      results of this study suggest that the effects of intraoperative analgesics may
      not be significant. Patients who had received the above mentioned anesthetic
      regimen intraoperatively also required full postoperative analgesia as well.

PMID- 23157088
TI  - [Effect of individualized goal directed therapy on outcome after major sugery].
AB  - BACKGROUND: Goal directed therapy (GDT) is applied during the initial
      resuscitation of sepsis, known as early goal directed therapy (EGDT). Recent
      studies in major abdominal surgery suggested that anesthetic management with GDT
      may decrease morbidity and hospital stay. We have utilized GDT in major invasive
      surgery such as pancreatoduodenectomy in November 2009. METHODS: In the
      anesthetic management of pancreatoduodenectomy, 11 patients managed by GDT were
      compared concerning postoperative hospital stay with 11 patients managed by
      conventional methods retrospectively. In our GDT protocol, we have set targets in
      mean blood pressure, oxygen saturation, and stroke volume variation, which is
      more individualized for each one. With falls below the target, fluid infusion,
      blood transfusions, and circulatory agonists were administered. In the
      conventional protocol, anesthesiologist managed the use of anesthetic agents,
      fluid infusion, blood transfusion, and circulatory agonist, through the
      observation of the operative field, blood pressure, heart rate and urine output.
      RESULTS: Patients utilizing the GDT showed shorter postoperative hospital stay
      (group GDT; 21.8 days vs conventional group; 32.6 days. P<0.05). CONCLUSIONS:
      Anesthetic management with goal-directed therapy, may have contributed to shorter
      postoperative hospital stay.

PMID- 23157089
TI  - [Use of the air-Q intubating laryngeal airway for tracheal intubation in
      predicted difficult airway management in a pediatric patient].
AB  - The intubating laryngeal airway, air-Q ILA, was recently introduced in Japan. It
      has been used in adult patients for difficult airway management; however, there
      are few reports available on its use in pediatric patients. We report the use of
      the air-Q ILA in predicted difficult airway management in a 16-month-old patient
      with Apert syndrome characterized by acrocephalosyndactyly undergoing a
      syndactyly operation. It was somewhat difficult to keep his airway with a
      facemask, and an air-Q ILA was inserted. Following the ventilation via air-Q ILA,
      tracheal intubation guided by a tracheal fiberscope was attempted through the air
      Q ILA. Five months after this operation, the patient again underwent the same
      operation. We managed his airway in the same way as previously, and the tracheal
      was intubated. This case shows that the air-Q ILA can be an alternative device in
      pediatric difficult airway management.

PMID- 23157090
TI  - [Three cases of latex allergy complicated with anaphylaxis during cesarean
      section].
AB  - We experienced three cases of latex anaphylaxis during cesarean section in one
      year. CASE: 1 A 26-year-old woman underwent emergency cesarean section. Combined
      spinal-epidural anesthesia was performed and drip infusion of cefazolin sodium
      was started before operation. After delivery, intravenous injection of
      methylergometrine maleate and intramyometrial injection of oxytocin were given.
      Eight minutes after delivery, she complained of dyspnea and edema of eyelids; no
      change in vital signs were noted. We suspected an anaphylactic reaction and
      administered antihistamines as well as methylprednisolone. Inhalation of beta
      stimulators and sevoflurane using a face mask improved her respiratory symptoms.
      CASE 2: A 25-year-old woman underwent emergency cesarean section. We noticed
      wheals involving her eyelids and legs after operation and administered
      methylprednisolone. CASE 3: A 23-year-old woman underwent elective cesarean
      section. Five minutes after delivery and oxytocin injection, she complained of
      edema of eyelids, facial erythematous edema, and dyspnea. We suspected latex
      anaphylaxis and stopped using latex products. Then, we treated her with
      antihistamines, methylprednisolone and beta-stimulators. The diagnosis of latex
      anaphylaxis was made by positive results of skin tests to latex and an increase
      in the levels of latex-specific immunoglobulin E. We conclude that cesarean
      section is an important risk factor for latex anaphylaxis.

PMID- 23157091
TI  - [Anesthetic management of hip joint fracture surgery in an elderly patient with
      giant pulmonary artery aneurysm].
AB  - We report anesthetic management of an elderly patient with giant pulmonary artery
      aneurysm undergoing hip joint fracture surgery. Preoperative chest computed
      tomography showed a main pulmonary artery aneurysm with a maximal size of 55 mm.
      Surgery was performed under spinal anesthesia and adequate sedation with
      propofol. Continuous infusion of milrinone, phosphodiesterase 3 inhibitors, was
      given intravenously during anesthesia. Hypoxemia and hypothermia were avoided for
      the purpose of preventing an increase in pulmonary vascular resistance. Surgery
      was uneventful because of anesthetic management considering pulmonary
      hypertension.

PMID- 23157092
TI  - [Anesthetic management of a patient with Creutzfeldt-Jacob disease undergoing
      tracheal separation].
AB  - We gave anesthesia for tracheal separation in a patient with Creutzfeldt-Jakob
      disease. The patient, a 33-year-old woman, was bedridden and unable to
      communicate, and was going to undergo a tracheal separation procedure for
      repeated bouts of aspiration pneumonia. After a tracheostomy with local
      anesthesia and sedation with propofol, general anesthesia was induced and
      maintained with propofol (1.5-3.0 microg x ml(-1), target controlled infusion)
      and remifentanil (0.05-0.15 microg x kg(-1) x min(-1)). We did not use an
      anesthetic apparatus from the standpoint of infection control, and provided
      manual ventilation with a disposable Jackson-Rees circuit. During the operation,
      an entropy monitor indicated alternating extremely low (0-10) and high (90-100)
      values without circulatory change, probably due to a previously existing
      electroencephalographic abnormality. The surgery was uneventful, and spontaneous
      breathing and eyelid opening occurred about 10 minutes after discontinuation of
      remifentanil and propofol. In such infected patients, abnormal prion proteins can
      exist outside of the central nervous system throughout the period of anesthetic
      management. Therefore, careful infection control must be undertaken, even if the
      surgical site is not directly related to the central nervous system.

PMID- 23157093
TI  - [Four cases of cardiac arrest during spinal anesthesia].
AB  - Incident rates of cardiac arrest are reported as being from 0.54 to 17.5 per
      10,000 (0.54-17.5/10,000) spinal anesthesia patients. In our hospital, four cases
      of cardiac arrest occurred in 903 spinal and combined spinal and epidural
      anesthesia patients over 15 months (44.3/ 10,000). Common denominators were ages
      below 60 years, ASA-PS 1, rapid onset of T10 blockade within 2 minutes and leg
      raising from 3 to 6 minutes after administration of hyperbaric bupivacaine and T4
      blockade. All patients recovered without any side effects. The conditions
      suspected of causing strong bradycardia leading to cardiac arrest are thought to
      be maintained parasympathetic activity, lack of blood volume before anesthesia,
      rapid progress of spinal blockade, decreased blood return to the heart by high
      spinal blockade (T4) and protective cardiac parasympathetic reflex (Bezold
      Jarisch reflex).

PMID- 23157094
TI  - [Successful resuscitation in a life-threatening obstetric hemorrhagic patient
      with hematocrit 3%: a case report].
AB  - We report a postpartum woman who suffered from obstetric bleeding after caesarean
      section. Her lowest hematocrit was 3% when a large amount of blood was lost.
      "Guidelines for management of critical bleeding in obstetrics" published by the
      Japanese Society of Anesthesiologists and four related academic societies was
      helpful for the resuscitation of the parturient. A systematic approach was
      effective for the care of women with major obstetric hemorrhage.

PMID- 23157095
TI  - [Unilateral temporary meralgia paresthetica after caesarean section: report of a
      case].
AB  - We report a patient who developed unilateral temporary meralgia paresthetica
      after caesarean section. A 28-year-old morbidly obese woman underwent caesarean
      section under combined spinal and epidural anesthesia. Intraoperative position
      was 5-degree head down lithotomy position. She noted pain and hypesthesia along
      the anterolateral aspect of the right thigh on the second postoperative day, when
      postoperative continuous epidural analgesia was stopped. The pain and sensory
      impairment resolved 8 days after surgery without medications.

PMID- 23157096
TI  - [Anesthetic management of a patient with thrombocytopenia induced by methotrexate
      undergoing emergent clipping surgery].
AB  - A 70-year-old woman underwent emergent clipping surgery for subarachnoid
      hemorrhage under general anesthesia. Her laboratory data showed thrombocytopenia
      (4.0 x 10(4) microl(-1)). She had taken prednisolone (3 mg x day(-1)) and
      methotrexate (MTX) (10 mg x week(-1)) for rheumatoid arthritis for the last 10
      years. Anesthesia was induced with remifentanil as well as propofol, maintained
      with remifentanil and sevoflurane in oxygen. The operation was performed
      uneventfully without platelet transfusion. Since the cause of thrombocytopenia
      was suspected to be MTX, we started rescue therapy by calcium folinate
      postoperatively. Platelet count was normalized two days later (11.6 x 10(4)
      microl(-1)). One month after the operation, she was discharged uneventfully.

PMID- 23157097
TI  - [Left internal jugular venipuncture in real-time ultrasound-guided pediatric
      central venous cannulation].
AB  - The right internal jugular vein (IJV) is usually selected for pediatric central
      venous cannulation (CVC); however, the left is rarely selected. We investigated
      cases of CVC through left IJVs from Apr to Nov of 2011. In all 82 patients with
      the median age of 11 months, height of 72.2 cm, and weight of 7.4 kg, right IJVs
      were selected first for real-time ultrasound-guided CVC. Right IJVs were with
      median width of 7.3 mm, length of 5.0 mm, and depth of 6.8 mm. After three failed
      attempts through the right IJVs in three patients (3.7%), of 2 to 9 months of age
      out of the 82 patients, 24 G puncture needles were successfully inserted through
      left IJVs with the first attempt. One of the three patients, of 9 months of age
      with a persistent left superior vena cava, had a thinner 2.6-mm-wide right IJV
      and a thicker 8.3-mm-wide left IJV It was difficult but successful to insert a
      0.018-inch guidewire in another patient due to a steep 90 degree angle between
      the left IJV and the brachiocephalic vein.

PMID- 23157098
TI  - [Use of dexmedetomidine in a critically ill patient with hyperactive delirium: a
      case report].
AB  - A 28-year-old male after a traffic accident was hospitalized with the abdominal
      pain. The abdominal CT showed deep hepatic injury. We immediately performed
      emergency transcatheter arterial embolization (TAE) and observed him in the ICU.
      His condition was stable for a while, but soon he became disoriented and
      restless. We diagnosed him with hyperactive delirium in the ICU and administered
      flunitrazepam and haloperidol but with no effect. Next, we used dexmedetomidine
      hydrochloride (DEX), which was effective on delirium. DEX is a potent and highly
      selective alpha2 adrenoreceptor agonist and has minimal respiratory depression in
      contrast to other sedatives. During sedation with DEX, it is easy to arouse
      patients with physiological stimulus. Both memory and cognition are reported to
      be maintained to a certain degree during sedation with DEX. Postoperative
      delirium has been reported to be less with DEX compared to other sedatives.
      Recent studies have revealed that delirium is one of the most frequent
      complications and an independent risk factor for prognosis in the ICU patients.
      DEX may be effective for controlling delirium and provide sufficient sedation
      without respiratory adverse effects in patients in the ICU.

PMID- 23157099
TI  - [Intravenous arginine vasopressin for two pediatric cases of pulmonary
      hypertension after congenital heart surgery].
AB  - We experienced two pediatric cases of severe pulmonary hypertension after
      congenital heart surgery. It was difficult to wean two cases from cardiopulmonary
      bypass for systemic hypotension concomitant with pulmonary hypertension
      reflactory to conventional therapy, including administration of adrenaline,
      nitroglycerin, milrinone, and/or inhalation of nitric oxide. In order to increase
      systemic arterial blood pressure and improve severe right heart failure, we
      administered arginine vasopressin (AVP) intravenously, which is a potent
      vasoconstrictor via V1 receptor. The dose of AVP was 0.0002 unit x kg(-1) x min(
      1). After administration of AVP, systemic arterial pressure increased markedly
      and pulmonary arterial pressure decreased slightly, and we succeeded in weaning
      the patients from cardiopulmonary bypass. No adverse effect with AVP was found.
      In conclusion, administration of AVP is a therapeutic option for treating
      systemic hypotension concomitant with severe pulmonary hypertension in pediatric
      congenital heart surgery.

PMID- 23157100
TI  - [Ultrasound-guided peripheral nerve block for high-risk patients with
      arteriosclerosis obliterans in lower limb surgery--a report of nine cases].
AB  - Most patients with arteriosclerosis obliterans (ASO) have severe complications
      such as coronary artery disease, congestive heart failure and chronic kidney
      disease. They receive long-term antithrombotic therapy which is a
      contraindication to neuraxial anesthesia. In this retrospective study, we
      reviewed nine high-risk patients with ASO (revised cardiac risk index more than
      three) who underwent an urgent lower limb surgery under ultrasound-guided
      peripheral nerve block (PNB). In all cases, intraoperative hemodynamic changes
      remained minimized. In eight of the nine cases, analgesics are not required until
      10 hours after the operation. No complication related to PNB occurred.
      Ultrasoundguided PNB for patients with ASO undergoing lower limb surgery can be a
      useful anesthetic technique, providing cardiovascular stability and good
      postoperative analgesia.

PMID- 23157101
TI  - [Severe hypotension and ventricular fibrillation during combined general and
      epidural anesthesia in a patient on major tranquilizers].
AB  - A 54-year-old man (height 155 cm, weight 49 kg) was scheduled for
      retroperitoneoscopic nephrectomy. He had a history of schizophrenia that had been
      controlled with propericiazine 10 mg and bromperidol 3 mg daily for 34 years.
      After induction of anesthesia, 1% mepivacaine 5 ml was administered via an
      epidural catheter. Blood pressure decreased 15 minutes later to 47/25 mmHg and
      heart rate dropped to 50 beats x min(-1). Ventricular fibrillation occurred
      despite titrated injection of ephedrine (40 mg total), phenylephrine (1 mg
      total), atropine (0.5 mg total), and rapid infusion of crystalloid and colloid
      solutions. Chest compression and defibrillation were required to restore
      spontaneous circulation. Surgery was cancelled and he was extubated 45 minutes
      later without any complications. These findings suggest that caution must be
      exercised when combining general and epidural anesthesia for patients on long
      term major tranquilizers. In the event of refractory hypotension, the use of
      direct-acting vasoconstrictors such as noradrenaline or vasopressin should be
      considered.

PMID- 23157102
TI  - [Use of the air-Q laryngeal airway and tube exchanger in a case of difficult
      tracheal extubation after maxillectomy].
AB  - A 79-year-old man was diagnosed with maxillary cancer and underwent total
      maxillectomy under general anesthesia. The oropharyngeal airway was needed for
      efficient mask ventilation during anesthesia induction. The maxilla was totally
      resected and reconstructed with skin from a femoral flap. Tracheal extubation was
      considered to be difficult given that mask ventilation was contraindicated due to
      reconstruction of the maxilla. After inserting a tube exchanger (TE) into the
      trachea, the tracheal tube was exchanged with an air-Q laryngeal airway through
      the TE. After confirming effective ventilation with the air-Q mask, the patient
      was awakened from anesthesia. We confirmed sufficient spontaneous breathing and
      no active bleeding in the pharynx. After re-inserting the TE thorough air-Q, the
      air-Q was removed, followed by removal of the TE. These findings suggest that the
      air-Q and TE were effective in a case of difficult extubation after maxillectomy.

PMID- 23157103
TI  - [ECG changes after the induction of general anesthesia with remifentanil: a
      report of three case].
AB  - We encountered three patients who showed ECG changes, suggesting cardiac
      conduction abnormality, immediately after the induction of general anesthesia
      with remifentanil and thiamylal. The first patient was a 42-year-old man (172cm
      and 75kg). The second patient was a 75-year-old woman (153 cm and 62 kg) and the
      last patient was 16-year-old woman (166 cm and 46 kg). Remarkable past history
      was not noted and pre-anesthetic evaluations including 12 lead electrocardiogram
      demonstrated no abnormality in all patients. Immediately after the induction of
      anesthesia, atrioventricular dissociation, sinus arrest and atrioventricular
      junctional rhythm were diagnosed by monitoring electrocardiogram, respectively.
      The conduction abnormalities were not followed by severe bradycardia and
      hypotension, and observed without drug administration. In the first and second
      patient, sinus rhythm returned within 15 to 20 min after the induction. The
      junctional rhythm in the third patient continued during the operation; however,
      the recovery to sinus rhythm was observed at the end of operation lasting about 1
      hr. No severe adverse clinical complication was found; however, careful
      monitoring might be required to pre vent circulatory depression with combination
      of remifentanil and thiamylal.

PMID- 23157104
TI  - [Patient with pseudomyxoma peritonei in whom, hyperglycemia and hyponatremia were
      induced by massive intraperitoneal lavage with 5% glucose].
AB  - A 74-year-old woman was admitted to our hospital with weight loss and sense of
      abdominal distension. She was diagnosed to have pseudomyxoma peritonei based on
      careful examinations in the surgical department of our hospital. She therefore
      underwent elective surgery consisting of an ileocecal resection under general
      anesthesia. The induction of anesthesia was very smooth, but the patient's blood
      pressure became unstable during the operation. As a result, we inserted an
      arterial catheter into the radial artery, and the blood gas analysis showed
      severe hyperglycemia and hyponatremia. We determined that a massive amount of
      intraperitoneal lavage fluid with 5% glucose had been absorbed into the blood
      vessels. We administered regular insulin to manage the hyperglycemia and also
      mannitol and furosemide to treat the hyponatremia that had been caused by water
      intoxication. Thereafter, both the hyperglycemia and hyponatremia improved
      quickly, and the patient was extubated safely. We had little prior knowledge
      about pseudomyxoma peritonei, and therefore had not expected such an occurrence.
      Moreover we did not sufficiently provide the surgical team with all of the
      patient's information. In the future, we will maintain close cooperation with the
      surgical team and establish an appropriate anesthesia plan when we encounter
      patients presenting with pseudomyxoma peritonei.

PMID- 23157105
TI  - [Case report of anesthesia with veno-veno extracorporeal membrane oxygenation (V
      V ECMO) during one-lung ventilation for acute respiratory distress syndrome
      (ARDS) complicated with severe sepsis due to spontaneous esophageal rupture].
AB  - A 55-year-old man was transferred to our hospital with spontaneous esophageal
      rupture. An emergency operation of mediastinum drainage by thoracotomy was
      performed. On postoperative day 8, he had new abcesses located at the upper
      mediastinum around the esophagus, and required another operation. But one-lung
      ventilation for the operation was difficult, because of profound hypoxia caused
      by the acute respiratory distress syndrome (ARDS) with severe sepsis. Therefore
      we introduced V-V ECMO for the treatment of severe hypoxia and could anesthetize
      him safely during surgical operation. Intraoperative and post-operative
      hemodynamics was stable. His respiratory condition improved, and he was weaned
      from V-V ECMO. Unfortunately, postoperative day 11, he died because of sudden
      intrathoracic bleeding from the thoracic aorta which might have been infected by
      the severe mediastinitis.

PMID- 23157106
TI  - [Fentanyl induced intraoperative anaphylactic reaction].
AB  - We report a case of intraoperative fentanyl anaphylactic reaction. The patient
      was a previously healthy 12-year-old boy with severe head injury by a traffic
      accident. We experienced a rapid hemodynamic change after fentanyl injection and
      that occurred again after another fentanyl injection. In the second hemodynamic
      change, red wheals appeared on the skin. We clinically diagnosed this as fentanyl
      anaphylactic reaction. Six weeks later we performed prick test and intradermal
      test, but the patient had negative results for fentanyl in both tests. Although
      it is rare that opioids cause anaphylactic reaction, we must differentiate them
      when we search causative agents. Even if skin tests are negative, there is a
      possibility of false negative reactions. Therefore it is safe to regard
      suspicious agents as causative agents in cases where the agents are clinically
      suspected.

PMID- 23157107
TI  - [Case of atonic bleeding managed by emergency total hysterectomy and mass blood
      transfusion right after the cesarean section].
AB  - A 34-year-old woman, who had had atonic bleeding six years ago, had selective
      cesarean section under CSEA. On the operation, atonic bleeding occurred and
      persisted. Though we used uterine contracting agents (oxytocin, ergometrine), the
      bleeding volume exceeded 2,000 ml and the examination revealed Hb 5.9 g x dl(-1),
      Ht 19%. We decided to perform emergency hemostatic operation (total hysterectomy)
      under general anesthesia. During the emergency operation, total blood loss was
      5,810 ml and total urine was 205 ml. We transfused packed red cell 16 units, FFP
      10 units, and infused fluid 4,650 ml. After the operation, the examination
      revealed Hb 9.7 g x dl(-1), Ht 27.8%, Plt 7.0 x 10(4) x microl(-1) and obstetric
      DIC score 10. The patient was treated in ICU under intubation, with anti-DIC drug
      (ulinastatin 50,000 units). Next day, she was extubated and admitted to the
      maternity ward. She was discharged on the 7th postoperative day without any
      complications. In 2010, guideline for obstetric critical hemorrhage was
      published. The guideline recommends the importance of observing the perioperative
      change of vital sign (e. g. shock index) and obstetric DIC score. In the
      obstetric critical hemorrhage, we should take proper and prompt actions in
      accordance with this guideline.

PMID- 23157108
TI  - [Case of acute exacerbation of neuropathic cancer pain rapidly relieved by
      simultaneous oral intake of immediate release oxycodone and pregabalin].
AB  - Cancer pain consists of continuous pain lasting almost all day and transient
      exacerbation of pain called breakthrough pain. Breakthrough pain is classified as
      somatic pain and visceral pain, neuropathic pain according to the character of
      pain. Although the immediate release opioid is used as the first treatment of
      choice to breakthrough pain, the effect is not enough when it shows the character
      of neuropathic pain. Pregabalin has become the first medicine for the treatment
      of neuropathic pain, and it sometimes reveals prompt analgesic effect based on
      its pharmacological profile. It has also been reported that pregabalin used with
      oxycodine reveals analgesic effect with smaller dosage than pregabalin alone. We
      experienced a young patient with lung cancer suffering from sudden exacerbation
      of symptomatic sciatica, whose pain was markedly reduced within 30 minutes by
      taking immediate release oxycodone 5 mg and pregabalin 75 mg simultaneously.
      Conclusions : Pregabalin with immediate release oxycodone simultaneously may be
      able to improve acute exacerbation of neuropathic cancer pain rapidly.

PMID- 23157109
TI  - [Effects of catheter size and fixation device on central venous catheter
      fixation].
AB  - The risk of accidental removal of a central venous catheter is a major concern in
      anesthesia and intensive care. We hypothesized that the force required to remove
      a fixed catheter depends on the size of the catheter (diameter) or use of a dry
      or wet catheter. In this study, the force required for accidental removal of dry
      and wet catheters was compared by dividing the subjects into 2 groups: dry group
      (patients in whom dry catheters were used) and wet group (patients in whom wet
      catheters were used). The force required for the accidental removal of dry
      catheters was greater than that required for the accidental removal of wet
      catheters, regardless of catheter diameter. Therefore, it is essential to use dry
      catheters and fixtures to prevent accidental removal of central venous catheters.

PMID- 23157110
TI  - [Introduction of a simple audio recording system to the operating room-
      experience at a small local hospital].
AB  - We developed a simple audio recording system using a small personal computer and
      free audio recording software that makes voice recordings for use in emergencies,
      particularly for emergency caesarean sections. The system makes a continuous
      audio recording while the patient receives medical treatment. The recording
      provides an accurate record of the anesthesia used during treatment. This audio
      recording system is useful as an auxiliary means of record keeping during medical
      emergencies.

PMID- 23157111
TI  - [Comparison of fibrinogen synthesis and secretion between novel variant
      fibrinogen, nagakute (gamma305Thr --> Ala), and other variants located in
      gamma305-308 residues].
AB  - We found and identified a novel heterozygous dysfibrinogenemia with gammaT305A
      (ACA --> GCA) mutation in a 6-month old boy. Since his plasma antigenic
      concentration of fibrinogen was 1.12g/l and less than the lower limit of the
      reference interval, we guessed that the production of a variant fibrinogen might
      be a partial defect. To clarify this speculation, we altered the gamma-chain
      expression vector, transfected it into Chinese Hamster Ovary(CHO) cells, and
      synthesized recombinant gammaT305A fibrinogen alongside three other variant
      fibrinogens, gammaS306P, gammaH307Y, and gammaN308K, and the wild type (gammaN)
      fibrinogen. Fibrinogen concentration ratio of culture media/cell lysates
      decreased in the order of gammaT305A-, gammaS306P-, gammaH307Y-CHO cells, all
      three being lower in comparison to the gammaN-CHO cells. Western blotting
      analyses indicated that all of variant gamma-chains were assembled into
      fibrinogen molecules in the cells. These data indicate the possibility that
      secretion of gamma T305A-fibrinogen is slightly impaired and variant fibrinogen
      is accumulated in the cell. Of interest, the secretion of gammaH307Y-fibrinogen
      was decreased the most, whereas that of the gammaN308K-CHO cells was not
      affected. The tertiary structure of the yC nodule indicated that gamma305T
      gamma307H residues are located in the inside of the nodule. In contrast, that of
      gamma308N is located on surface of the nodule. In conclusion, our results showed
      the variant fibrinogen, gammaT305A, has characteristics not only of
      dysfibrinogenemia, but also might be hypofibrinogenemia, namely,
      hypo/dysfibrinogenemia. Furthermore, gamma306S-gamma307H residues of the gammaC
      nodule play crucial roles for protein synthesis and fibrin polymerization.

PMID- 23157112
TI  - [Characterization of unusual macro CK1 of IgG3kappa-cK-MM type detected in the
      serum of a patient with idiopathic thrombocytopenic purpura].
AB  - An unusual creatine kinase (CK) band detected in the serum of a patient with
      idiopathic thrombocytopenic purpura (ITP) was studied. The number of platelets of
      the patient decreased to 2.3 x 10(4)/microL, and serum CK and CK-MB activities
      increased to 899 and 62.7 U/L, respectively. The unusual CK band with a molecular
      size of 320,000 migrated to the cathodal side of CK-MM through electrophoresis,
      and the position was similar to that of octameric mitochondrial CK(Mi-CK).
      However, the cathodal band did not react with anti ubiquitous or anti-sarcomeric
      Mi-CK antibodies; instead, a reaction of the band occurred with anti-CK-M subunit
      antibodies and CK activity was inhibited. In addition to the cathodal band of CK
      MM, an atypical CK band was simultaneously detected on the anodal side of CK-MM.
      It was found that the cathodal and anodal bands were macro CK1 of IgG3kappa-CK-MM
      and IgG1kappa-CK-MM, respectively, by immunofixation electrophoresis with anti
      IgG subclass antibodies. The number of platelets began to increase one week after
      the elimination of Helicobacter pylori. The cathodal band activity showed an
      opposite migration one to two weeks following the platelet count change. Change
      of the anodal band began one month or longer following the platelet count change.
      One year following the first medical examination, the level of IgG3 in the serum
      of the patient decreased to 45%, and the percentage was lower than those of the
      other IgG subclasses. These results suggest that changes in the cathodal band are
      associated with those of the number of platelets and reflect the disease state of
      the patient. In conclusion, the cathodal band of CK-MM in the serum of an ITP
      affected patient was macro CK1 of IgG3kappa-CK-MM type, it migrated to the
      opposite sides of the platelet count change, and reflected the disease state of
      the patient.

PMID- 23157113
TI  - [A case of epilepsy with ring chromosome 20 syndrome].
AB  - A case of epilepsy associated with ring chromosome 20 [r(20)] syndrome was first
      reported in 1972. Relatively few cases of [r(20)] syndrome have been reported. We
      report here a middle-aged female with this syndrome. She had two types of
      seizures characterized by complex partial seizure with complex motor automatism
      mainly occurred while asleep and episodes of fluctuating consciousness (non
      convulsive status epilepticus) lasting 40-60 min. The ictal
      electroencephalography (EEG) findings of the latter showed almost continuous
      diffuse spike and wave complexes or high voltage slow waves. The interictal EEG
      findings showed spike or sharp waves located in bilateral frontal regions or 3
      6Hz diffuse high voltage slow waves intermingled with spikes in left posterior
      areas. We reviewed and discussed the characteristics of [r(20)] syndrome reported
      in the literature, intractable seizures, behavioral problems and some degree of
      mental retardation or dysmorphism, especially variable EEG findings characterized
      this syndrome.

PMID- 23157114
TI  - [Introduction of preventive measures toward contact infection without affecting
      the efficiency of the outpatient blood collection].
AB  - At the University of Tokyo Hospital, an average of 956 venopunctures/day was
      performed for outpatients in the period between 2008 and 2011. At the outpatient
      clinic, the collection of blood without delay, and the prevention of contact
      infection, are always important matters to be addressed. For the prevention of
      infection, changing gloves, and wiping of tables and tourniquets with antiseptic
      cotton, for each patient has been performed since August 2010. Because the time
      required for each blood collection was prolonged about 19 sec., after the
      introduction of these preventive measures, we analyzed the factors which affected
      the waiting time at the blood collection room. The waiting time required for the
      blood collection between period of August and October, 2010, i.e., after the
      introduction of the preventive measures, was analyzed and compared with that
      between August and October, 2009, as the control. After the implementation of the
      preventive measures, the percentage of patients with waiting time of blood
      collection shorter than 10 min decreased from 73% to 58%. Thus, to improve the
      efficiency of blood collection and shorten the collection time, one collection
      booth was added, and the blood collection procedure was standardized. Also, the
      number of outpatients waiting for phlebotomy and the number of available
      phlebotomists are automatically transferred from the computer system for blood
      collection to the laboratory computer system, which, based on these data,
      displays an alert for the need of additional phlebotomists, when required. By the
      implementation of these measures, the percentage of patients with waiting time
      shorter than 10 min increased from 73% to 83%. From the present results, we
      considered that the preventive measures against contact infection could be
      successfully implemented, without affecting on the waiting time, and
      consequently, efficient management at the outpatient clinic could be achieved.

PMID- 23157115
TI  - [Comparison of the performance of the ECLusys anti-HCV reagent with the Lumipulse
      f and HISCL 2000-i HCVAb assays].
AB  - We compared the ECLusys Anti-HCV (ECL) reagent to the Lumipulse f (LPf) and HISCL
      (HIS) HCV assays. In a correlation test using 210 routine clinical specimens
      measured using the Lumipulse method (96 positive and 114 negative), most of the
      results were consistent for all specimens. In a dilution sensitivity test using
      three different routine positive specimens, the ECL assay enabled detection at
      higher levels of sensitivity than either the LPf or the HIS assay. Moreover, when
      the distribution of the cut-off index (C.O.I.) values of the routine LPf negative
      specimens were compared to those on the ECL and HIS assays, it was found that on
      the ECL assay, most of the specimens had cut-off index values < 0.1, indicating a
      more clear-cut distribution. In a specificity test using high RF positive
      specimens(n = 33), pregnancy specimens (n = 35), cytomegalovirus (CMV) antibody
      positive specimens (n = 36), and high M protein positive specimens (n = 21), the
      ECL assay yielded positive results for a CMV antibody positive specimen and three
      high M protein positive specimens. Further testing using samples from the same
      patients collected on different days than these four samples resulted in a second
      positive result for the CMV positive specimen, and single antigen measurement
      yielded a Core/NS3 positive result, as well, suggesting past infection. However,
      since negative results were obtained for the three M protein positive specimens,
      the possibility of this being a ECLusys non-specific reaction could not be ruled
      out. The above results confirmed that the ECL assay provides superior fundamental
      performance, and possesses test performance nearly identical to that of the
      existing measurement methods that are widely used at a large number of
      facilities, and would therefore be a suitable assay for use in routine HCV
      antibody screening.

PMID- 23157116
TI  - [Echocardiography as physiological function examination].
AB  - Echocardiography is one of the most important examinations in patients with heart
      disease. Since high temporal resolution is necessary to assess the function of a
      "beating heart", there is no alternative modality, such as cardiac-CT or MRI.
      Patients are assessed for their cardiac functions, i.e., left ventricular
      systolic and diastolic function, and valvular function with blood flow velocity
      by echocardiography. Using newly developed equipment, including portability, we
      also examined cardiac function by 3D echocardiography and the speckle tracking
      method. Echocardiography plays an important role in the diagnosis and assessment
      of physiological function in heart disease patients; however, it depends on the
      sonographer's skill and knowledge whether it is possible to obtain important and
      valuable information by echocardiography. It is necessary to plan a systematic
      educational program for residents and sonographers.

PMID- 23157117
TI  - [Pulmonary function testing in Japan: present status and new developments].
AB  - In 2004, the Japanese Respiratory Society issued an initial set of
      recommendations on the standardized measurement of the most frequently used tests
      for pulmonary function, i.e., tests to assess slow vital capacity, forced vital
      capacity, and single-breath carbon monoxide diffusing capacity. This statement
      has not been updated, and the prediction equations for pulmonary function testing
      are not fully established. Thus, the guidelines will need to be periodically
      updated in accordance with new developments in this rapidly evolving field.
      Nitric oxide (NO) is now recognized as a biological mediator in animals and
      humans. The human lung produces NO and exhales it in breath. The fractional
      nitric oxide (NO) concentration in exhaled breath (FE(NO)) can be quantitatively
      measured by a simple, safe, and noninvasive procedure as a complementary tool for
      assessing airway inflammation in airway diseases such as asthma. While the
      measurement of exhaled NO is standardized for clinical use, FE(NO) measurement is
      not approved or covered under the public health insurance system in Japan.

PMID- 23157118
TI  - [How to use echocardiography in clinical practice in cardiology].
AB  - Echography is an essential diagnostic tool in cardiology. Recent advancements
      have further increased the potential of echography. 3D echo assessment of LA and
      LV volumes and LV mass index LA volume index and LV end systolic volumes are
      easily obtained with 3D echo, and are useful for risk stratification among
      patients with heart failure. LV mass index, which is also measured with 3D echo,
      reflects time-integral exposure of the heart to risk factors, such as
      hypertension, DM, CKD and so on. Increased LV mass index is associated with a
      higher risk of cardiovascular events. Quantitative evaluation of regional
      myocardial function with automated functional imaging (AFI) AFI is based on the
      speckle tracking method and quantitates wall motion abnormality. AFI provides a
      strain map of the left ventricle in a color-coded bull's eye image. Assessment of
      endothelial function with flow-mediated dilation (FMD) FMD reflects endothelial
      function to produce nitric oxide in response to an increase in blood flow.
      Decreased FMD, which implies endothelial dysfunction, is an initial step in
      atherosclerosis. FMD-guided therapy may be a new trend in the prevention of
      atherosclerosis.

PMID- 23157119
TI  - [Vascular function tests and new technology in the early phase of
      atherosclerosis].
AB  - The present topic of vascular function concerns how we detect the earliest
      arteriosclerotic changes. If we could diagnose the early phase of
      atherosclerosis, we would be able to intervene to prevent cardiovascular events
      caused by atherosclerosis. Recently, it became possible to examine vascular
      function non-invasively by pulse wave velocity (PWV), the augmentation index (AI)
      and flow-mediated dilatation (FMD) of the brachial artery induced by reactive
      hyperemia. Carotid ultrasonography is used to observe the morphological change
      and arterial stiffness of the carotid artery. This review focuses on the relation
      between arterial function tests and diseases, the method for measuring vascular
      function, and new technology for arterial stiffness.

PMID- 23157120
TI  - [The current status and view of the future of abdominal and superficial organ
      ultrasonography].
AB  - Ultrasonography, one of the physiological function examinations, is essential to
      practical medicine. It is superior to CT and MRI in safety, as well as real-time
      and spatial resolution. Diagnostic ultrasound is usually performed in B-mode and
      Doppler-mode. In addition to these modes, elastography and contrast-enhanced
      ultrasonography have sometimes been used for further examination. Recently,
      ultrasonography with a new application for diagnosis and therapy and unique
      technology are being watched with interest. The current status and view of the
      future regarding abdominal and superficial organ ultrasonography will be
      introduced.

PMID- 23157121
TI  - [Present status and future development of neurophysiological examination in
      laboratory medicine].
AB  - In 2011, nine brain and six nerve and muscle physiological examinations were
      covered by the national health insurance in Japan. The greatest recent change was
      the digitalization of electroencephalography in the neurophysiological
      laboratory. This change is good for hospital affairs both economically and
      ecologically. Board certified doctors or technologists by the Academic Society in
      Neurophysiology are increasing each year and are improving the clinical level in
      daily laboratory work. One problem is that the level of neurophysiological
      laboratory examinations differs among hospitals in Japan, but they are showing a
      gradual improvement. Future development is promising in this field. Technological
      progress in neurophysiological functions is remarkable, including magnetic
      methods. Magnetoencephalography has powerful spatiotemporal resolution and can
      analyze higher brain function such as language, memory, calculation and so on.
      Transcranial magnetic stimulation is also available for laboratory examination of
      the nervous system, including motor and higher brain functions. In this symposium
      we showed cerebellar-related motor potentials in the soleus muscle by
      transcranial magnetic stimulation of the posterior fossa. This report summarizes
      the present status and future development of the neurological field in
      physiological laboratory examinations.

PMID- 23157122
TI  - [Self-injury in Japan: epidemiological features from the nationwide survey data
      of 2010].
AB  - OBJECTIVES: The purpose of this study was to examine the epidemiological features
      of self-injury in Japan, and to investigate the factors associated with a history
      of self-injury, using nationwide random sample data on Japan in 2010. METHODS:
      Questionnaires were distributed to 2,693 subjects, aged 16-49 years, randomly
      selected from the all over Japan using 2-stage stratified random sampling; the
      answers regarding self-injury were analyzed. Potential risk factors were compared
      between those who answered that they had a history of self-injury (self-injury
      group) and those who answered that they did not (non-self-injury group). RESULTS:
      Responses were obtained from 1,540 participants (response rate, 57.2%). Lifetime
      prevalence of having 1 or more self-injury events was 7.1% overall (3.9% for men;
      9.5% for women) and approximately half of them reported a repetitive history of
      self-injury. Lifetime prevalence of self-injury was highest in those aged 16-29
      years (9.9%, 16-29 years; 5.6%, 30-39 years; 5.7%, 40-49 years). Lifetime
      prevalence among women (16-29 years, 30-39 years, and 40-49 years) decreased with
      age (15.7%, 7.5%, and 5.8%, respectively), however, that among men increased with
      age (3.0%, 3.4%, and 5.5%, respectively). Compared with the non-self-injury
      group, those in the self-injury group were significantly more likely to have a
      history of cigarette smoking (self-injury group, 47.5%; non-self-injury group,
      28.2%; adjusted odds ratio [95% confidence interval]: 2.18 [1.32-3.58]),
      childhood abuse (23.6% and 3.7%, respectively, 4.24 [2.18-8.25]), induced
      abortion (30.3% and 12.7%, respectively, 1.93[1.13-3.30]); moreover, they were
      significantly less likely to answer that they had a happy life when they were
      junior high school students (41.1% and 78.6%, respectively, 0.45 [0.25-0.79]). In
      addition, those in the self-injury group were more likely to report a history of
      parental divorce, that they did not have good communication with their parents,
      and that they did not have respect and appreciation for their parents; however,
      these factors were not significant after adjustment. CONCLUSION: These results
      are consistent with those of previous research reports in which the lifetime
      prevalence of self-injury was high among women aged 16-29 years, and in which
      self-injury was more likely to occur among individuals who had a history of
      cigarette smoking and childhood abuse. Such individuals should be provided care
      to prevent self-injury. In addition, from a social point of view, research
      examining family environments including these factors is required.

PMID- 23157123
TI  - [Subjective daytime sleepiness in community-dwelling elderly in Japan].
AB  - OBJECTIVES: The objective of this study was to assess the prevalence of
      subjective daytime sleepiness among the community-dwelling elderly population in
      Japan using the Japanese version of the Epworth Sleepiness Scale (JESS) and to
      investigate the correlates of excessive daytime sleepiness (EDS). METHODS:
      Subjects aged 65 years or older, born between April and September, living
      independently, who resided in 1 district of Tokyo, Japan, were recruited. A total
      of 3195 subjects meeting the inclusion criteria were mailed a questionnaire that
      inquired about the JESS, socio-demographic factors, and health-related factors.
      Of the 2034 elderly individuals who responded to the survey (response rate,
      63.7%), 1494 subjects (652 men, 842 women) who completely answered the
      questionnaire were included in the study (valid response rate, 46.8%). RESULTS:
      The mean (+/- standard deviation) JESS score was 5.0 +/- 3.8 (men 5.6 +/- 4.1,
      women 4.4 +/- 3.4, P <0.01). The prevalence of EDS (a cut-off score>10) was 8.8%
      (men 12.7%, women 5.7%, P< 0.01). The male gender, being employed, having poor
      mental health and well-being, having lowered activity of daily living (ADL), or
      having subjective memory impairment were significantly associated with EDS. In
      the gender-specific models, low social network and subjective memory impairment
      in men, whereas obesity and lowered ADL in women, were significantly associated
      with EDS. CONCLUSION: EDS was more frequently observed in men than in women among
      the community-dwelling elderly population in Japan. A substantial gender
      difference was found in correlates of EDS. This finding is useful in the clinical
      management of patients who complain of daytime sleepiness; moreover, it is useful
      for the management of public health.

PMID- 23157124
TI  - [Evaluation of the flu call center and medical system data on pandemic (H1N1)
      2009 influenza. Comparison of cases in Kobe city and Ibaraki prefecture].
AB  - OBJECTIVES: To make recommendations on the revision of the Pandemic Influenza
      National Action Plan and Guidelines, we reviewed the data from the flu call
      center and medical institutions in Kobe city and compared them with data from
      Ibaraki prefecture. METHODS: The overall duration of study from May 2009 to
      December 2009 was divided into 4 periods; we analyzed details of the calls
      received by the call center and examined the correlation between them and cases
      who were seen at medical institutions in Kobe. We used a mathematical model to
      approximate the cumulative growth curve of the number of calls received by the
      call center and the number of cases attending fever clinics in Kobe. We compared
      the above data with data from Ibaraki because the total number of confirmed cases
      of pandemic (H1N1) 2009 influenza was similar: Kobe identified the first
      confirmed case of the influenza in Japan, while Ibaraki reported their first case
      1 month later. RESULTS: Following the report of the initial domestic case, the
      Kobe call center received 30,067 calls in a month. A "delayed sigmoid curve"
      fitted well for both the rise in the number of calls at the call center and of
      cases attending the fever clinics. "Feeling sick despite no overseas travel
      history" was the most common reason for call. More than 2,000 calls/day were
      received, and the responses to such calls were instructions to consult a general
      medical institution (40%), instructions to refer to a fever clinic (8%), guidance
      on home care or how to manage underlying disorders, and listening to callers'
      anxieties and complaints. The numbers of calls decreased towards the end ofJuly;
      the number of calls increased again when outbreaks were reported in schools and a
      death due to influenza was confirmed. After November, on an average, 500
      calls/day were received; most were complaints regarding vaccination. Unlike Kobe,
      Ibaraki did not experience a surge in the number of calls to the call center or
      consultations to fever clinics within a short period of time. CONCLUSION: The
      outbreak of pandemic (H1N1) 2009 influenza showed different call patterns and
      medical consultations in different regions. The time of disease outbreak and the
      availability of medical resources differ among regions; hence, each municipality
      should act practically and flexibly according to the situation in their locality.

PMID- 23157125
TI  - [Surveillance for food poisoning of unknown origin derived from fresh seafood in
      Japan in 2009].
AB  - OBJECTIVES: The frequency of food poisoning from fresh seafood in Japan in 2009
      and the regional characteristics and causative factors of such poisoning require
      investigation. In all cases, no bacterial or viral pathogens have been detected,
      although sliced raw flounder (sashimi) was suspected as being causative by the
      food sanitation inspectors. However, the cause of these poisonings is still
      unknown, and comprehensive approaches are required to completely understand the
      problem. METHODS: In order to obtain information on these poisonings, we sent a
      questionnaire to all 136 autonomies in Japan. It was found that many patients had
      contracted such poisoning. Symptoms included vomiting/nausea, diarrhea, and
      abdominal pain. Symptoms generally began within 12 hours of eating fresh seafood
      and resolved by the next day. The period of this survey was from January 1, 2009
      to December 31, 2009. We analyzed the data by year and month and investigated the
      regional incidence. RESULTS: The response rate was 72.8% (99/136). Seventy
      autonomies answered "yes" and the remaining 29 answered "no." There were 57 cases
      of definite and 171 cases of suspected food poisoning. Since 2003, the number of
      poisonings has increased annually, and they occur throughout the year, although
      they are most common in September in all autonomies. The highest incidence
      (53.9%) was reported for August, September, October, and November. CONCLUSION:
      Food poisoning of unknown origin from fresh seafood in Japan shows seasonal
      characteristics, being more common during the hot seasons than in the cold
      seasons. When a pathogenic substance is not discovered, it is very difficult to
      confirm food poisoning, which is why the number of suspected cases was 3 times
      that of the confirmed.

PMID- 23157126
TI  - [Applicability of the dietary record by cooked dishes method for estimating
      dietary intake of populations in the areas other than where the database was
      developed].
AB  - OBJECTIVES: The Dietary Record by Cooked Dishes (DRcd) method, which enables
      simple assessment of food and nutrient intake, is unique because it uses a
      nutrient database of cooked dishes. Although this method has been validated among
      the rural Japanese populations for which the database was developed, the
      applicability of the DRcd for other populations is unclear. In this study, we
      have examined the applicability of DRcd among an urban population. METHODS:
      Subjects were selected from among patients who underwent cancer screening between
      2004 and 2006 at the Research Center for Cancer Prevention and Screening,
      National Cancer Center, Japan. Subjects aged 40-69 years, who lived in Tokyo and
      the surrounding suburbs, were stratified into groups by sex and age. A total of
      144 men and women agreed to participate in the study after random selection.
      Subjects were instructed to keep 4-day dietary records (4d-DR) of all consumed
      foods and beverages, including dish names, and all dishes were then coded using
      DRcd codes on the basis their names. The intake of 17 food groups and 40
      nutrients was estimated using the dish-based nutrient composition table of the
      DRcd. Simultaneously, 4d-DR were used to calculate dietary intake independently,
      which served as a reference. We examined the applicability of the DRcd method
      using percentage difference and Pearson's correlation coefficients for intakes
      estimated using 4d-DR and the DRcd. Moreover, the results were compared to those
      of a previous study. RESULTS: A total of 88% of the recorded dishes matched the
      dish codes of the DRcd database by name. Pearson's correlation coefficient scores
      of 0.6 or higher were observed for 12 and 10 food groups, and for 34 and 27
      nutrients in men and women, respectively. Notably, the intake of majority of the
      nutrients tended to be underestimated, a difference that was more pronounced in
      men. In comparison with a previous study, the percentage differences and
      Pearson's correlation coefficient scores for intake tended to be lower in our
      study. CONCLUSION: As the correlation coefficients (0.6) were high for a majority
      of food groups and nutrients estimated by DRcd, the DRcd method may be applicable
      for urban populations. However, regional intake data may be necessary for the
      estimation of absolute value for the intake of some nutrients.

PMID- 23157127
TI  - [The current status of small bowel transplantation: a first case report of
      cadaveric small bowel transplantation in Kyushu area].

PMID- 23157128
TI  - [Remote radiation planning support system].
AB  - We constructed a remote radiation planning support system between Kyushu
      University Hospital (KUH) in Fukuoka and Kyushu University Beppu Hospital (KBH)
      in Oita. Between two institutions, radiology information system for radiotherapy
      division (RT-RIS) and radiation planning system (RTPS) were connected by virtual
      private network (VPN). This system enables the radiation oncologists at KUH to
      perform radiotherapy planning for the patients at KBH. The detail of the remote
      radiation planning support system in our institutions is as follows: The
      radiation oncologist at KBH performs radiotherapy planning and the data of the
      patients are sent anonymously to the radiation oncologists at KUH. The radiation
      oncologists at KUH receive the patient's data, access to RTPS at KBH, verify or
      change the radiation planning at KBH: Radiation therapy is performed at KBH
      according to the confirmed plan by the radiation oncologists at KUH. Our remote
      radiation planning system is useful for providing radiation therapy with safety
      and accuracy.

PMID- 23157129
TI  - [High mobility group box I (HMGB1) and its effect on dendritic cells].
AB  - It is known more and more about immunological mechanisms and one of the newly
      discovered events is a participation of alarmin in human immunology. One of them
      is high mobility group box 1 (HMGB1) which by their proinflammatory properties
      and influence on immune cells plays an important role in the pathogenesis
      inflammatory and infectious diseases. It is assumed that antibodies against HMGB1
      or HMGB1 inhibitors with antibodies anti-TNF-alpha will form the core of a
      specific anti-inflammatory therapy. The mobilization of dendritic cells (DCs)
      from peripheral tissues is critical for the establishment of T cell-dependent
      immune responses which take place in lymph nodes. The autocrine/paracrine release
      of HMGB1 controls the outcome of the DC-T cell interaction. In this paper we
      present the role of HMGB1 on dendritic cells in the context of pathogenesis
      inflammatory diseases.

PMID- 23157130
TI  - [Effectiveness of RF ablation of ventricular ectopic beats from the right and
      (or) left ventricle].
AB  - There are few studies on the immediate and long term efficacy of ablation of
      ventricular ectopic beat (VEB) using different mapping systems arrhythmia. The
      aim of the study was to evaluate the efficacy of intraoperative, immediate and
      late outcome of RF ablation ventricular arrhythmias and a comparison of methods
      for identification and ablation of arrhythmia substrate. MATERIAL AND METHODS: In
      88 patients, average age 50,8+/-17,8 years old (16 to 90) with performed RF
      ablation of VEB from the left ventricular and (or) right ventricular. We
      retrospectively evaluated surgical reports and clinical records. The number of
      applications, energy, temperature, duration of application, impedance, radiation
      exposure to X-ray and the presence of obesity, myocardial infarction were
      evaluated. RF ablation was performed using the method of Carto or Carto and Pace
      mapping stimulation or Pace mapping stimulation alone. Patients were divided into
      3 groups: group A - long result was positive after ablation, group B - treatment
      was ineffective, group C - ad hoc and postoperative result were positive but long
      result was negative. RESULTS: The observation time was 30+/-11 months (3-48). An
      ad hoc positive end point of VEB ablation was 86%, postoperative 74%, and a
      distant 60%, respectively. There was 13% ineffective treatments. Carto system was
      used in 53 patients. In 6 (11%, group B) treatment was ineffective, the remaining
      47 patients achieved complete success in 31 (58%, group A) cases, while temporary
      success in 16 (30%, group C) cases. The relationship between the average
      temperature of 57 Celcius degree during ablation (HR = 1.148, regression = 0.138,
      p < 0.039) and the effectiveness of treatment was found. No statistical
      significance between the assessment of the effectiveness of ablation of
      arrhythmias and the location of the substrate were found but there was no
      statistical difference between the analyzed parameters and the technical and
      clinical effectiveness of ablation in the method of localization of arrythmia.
      The highest percentage of ablation failures in follow-up concerned the technique
      Carto alone (34%), the most effective was combined techniques adding Pace mapping
      plus Carto (76% succes rate long after ablation). CONCLUSIONS: To find substrate
      of arrhythmia to ablate operator should be guided by stimulation mapping and
      electroanatomical map in order to achieve distant effect of operation. The only
      significant parameter correlating with the distant ablation efficacy was the mean
      temperature of the ablation. While using Carto to ablate arrythmia most important
      role is played by the precise location of the arrhythmia substrate rather than
      increasing the temperature during ablation.

PMID- 23157131
TI  - [Frequency of anemia in ulcerative colitis in children].
AB  - Anemia is one of most frequent complication of ulcerative colitis. It affects
      patients in the exacerbation of the disease as well as in the remission. It may
      be caused by the loss of the blood, the disturbances of intestinal absorption or
      deficient diet. The aim of the study was to estimate the rate of anemia in
      children with ulcerative colitis during first hospitalization. MATERIAL AND
      METHODS: The study comprised 36 children aged 2.5 to 18 years, 23 girls and 13
      boys in whom ulcerative colitis was diagnosed based on the Porto criteria. Anemia
      in children was assessed depending on the age, period between first symptoms and
      diagnosis of the disease and on the activity of the disease according to PUCAI
      scale. RESULTS: Anemia was diagnosed in 72.2% of the children. Hemoglobin
      concentration ranged from 6.3 to 12.4 g/dl, average 10.05 g/dl depending on age.
      Activity of the disease according to PUCAI scale amounted to 5 to 80 points,
      average 51.9 points. Time from first symptoms to the diagnosis of the disease
      extended from one week to 12 months, average 3.6 months. In children without
      anemia the average concentration of hemoglobin was 13.2 g/dl, the activity of the
      disease 33.5 points and average time before diagnosis - 1.7 months. CONCLUSIONS:
      Anemia is a frequent symptom of ulcerative colitis in children. The presence of
      anemia depends on the disease activity and on the time between first symptoms and
      diagnosis of the disease. There is a necessity of iron supplementation in
      children with anemia despite effective anti-inflammatory treatment.

PMID- 23157132
TI  - [Occurrence of autoantibodies in patients with alcoholic liver disease].
AB  - Autoantigens are present in normal cells and tissues. However, in physiological
      conditions autoantigens pose no danger due to the phenomenon of immunologic
      tolerance. The loss of immunologic tolerance and following autoagression could
      result from the structure changes of autoantigens as an effect of the activity of
      chemical factors, such as acetaldehyde, which is metabolite of ethanol. The aim
      of the study was to evaluate of occurrence of autoantibodies in patients with
      alcoholic liver disease. MATERIAL AND METHODS: Ninety-five patients with chronic
      alcoholic liver disease and 16 healthy controls were enrolled in this study. The
      presence of autoantibodies against liver proteins were assessed. The occurrence
      of studied autoantibodies was evaluated with regard to the degree of liver
      damage. Inclusion criteria were: age over 21 yrs, at least 3-yrs history of
      alcoholic liver disease, HBV and HCV-negativity, absence of autoimmunological
      diseases. The presence of autoantibodies AMA-M2, SLA/LP, LKM-1, LC1, anti-F
      actin, desmin and miozin in serum was assessed by immunoblotting method and ANA
      by ELISA. RESULTS: Autoantibodies were demonstrated in sera of 33% of patients.
      Single isolated autoantibodies were present in 24% of patients, whereas 9% of
      patients have several autoantibodies. The most prevalent were anti-F-actin (19%)
      and antinuclear antibodies (11%). Occurrence of anti-F-actin antibodies increased
      with degree of liver damage. CONCLUSIONS: Concluding these results suggest that
      alcohol may contribute to the activation of autoimmune processes, and
      particularly against contractile filaments of cells for which F-actin antibodies
      are produced.

PMID- 23157133
TI  - [Family history of alcohol abuse - depressive symptoms and the quality of life in
      view of the MAST score of schizophrenic patients with dual diagnosis].
AB  - The aim of the study was to investigate the influence of familial alcohol abuse,
      depressive symptoms and the quality of life on MAST score in schizophrenic
      patients, dependent from alcohol. Material and methods. 61 patients with dual
      diagnosis and 60 with single diagnosis of schizophrenia performed MAST In two
      groups with clinical scales, depressive symptoms and the quality of life were
      assessed. RESULTS: Significant correlates of higher MAST scores were family
      history of alcohol abuse and earlier onset of alcoholism. Dissatisfaction with
      the quality of life was correlated with higher MAST scores but only in dependent
      from alcohol female schizophrenic patients. CONCLUSIONS: Symptoms of depression
      accompanying alcohol dependence did not influence MAST score.

PMID- 23157134
TI  - [Rare causes of Cushing's syndrome].
AB  - Endogenous Cushing's syndrome seems to occur more frequently than previously
      anticipated. Both its initial diagnosis and differential diagnosis of the
      underlying disorder is undoubtedly challenging but important to identify
      sufferers among high-risk patients with disorders potentially related to cortisol
      excess. Apart from pituitary adenoma, adrenal tumor and ectopic ACTH secretion,
      there are a lot of disorders which rarely result in excessive glucocorticosteroid
      release and action. Remarkable progress in the area of hormonal assessment,
      imaging procedures and molecular biology has improved the diagnosis,
      differentiation and management of various clinical entities associated with
      development of Cushing's syndrome and let to the identification of some new
      disorders. Because these disorders may negatively affect survivals and, if not
      treated, lead to serious complications, it is essential to consider their
      presence in a differential diagnosis of various symptoms. The aim of this
      manuscript was to provide an overview of the contemporary etiopathogenesis,
      diagnosis and treatment of rare forms of Cushing's syndrome.

PMID- 23157135
TI  - [Predictive factors of virological response in chronically HCV infected].
AB  - Research on new antivirals drugs applied in the treatment of chronically HCV
      infected indicate that even the most perfect therapeutic molecules do not
      guarantee 100% efficacy. Since the beginning of the history of HCV infection
      treatment clinicians looked for predictors of treatment efficacy. Numerous
      studies confirm the high probability of cure in patients who cleared
      HCVinfectional 4 and 12 weeks of therapy. However despite of viral factors,
      recent research demonstrated predictive role of some host dependent factors. The
      most important role seems to play genetic factors including polymorphism
      rs12979860, as well as chemokins including first of all CXCL10 (IP-10). Very
      interesting seems to be also results of studies on association between vitamine D
      concentration and treatment efficacy. However in the future the most important
      predictive factor remain probably early on-treatment viral response.

PMID- 23157136
TI  - [Epidemiology and risk factors of the prostate cancer].
AB  - Prostate cancer is the most common malignancy of male genital organs. The
      etiology of the disease is complex and remains mainly unclear. The only
      established risk factors are advancing age, ethnicity and genetics, including
      changing in expression of ELAC2, RNASEL, MSR1 and HOXB13 genes as well as low
      number of CAG repeats in the androgen receptor gene. There are number of
      coexisting environmental risk factors, such as eating habits mostly diet reach in
      animal fats. An early sexual initiation and sexually transmitted infections, both
      viral (HSV-2, HPV-18 and -16, CMV) and bacterial (Neisseria gonorrhoea, Treponema
      pallidum, Chlamydia trachomatis) were also included. The etiology of prostate
      cancer also involves the influence of hormones - androgens and estrogens, as well
      as chronic inflammation of the prostate. In contrast to the incidence rate, which
      varies significantly depending on the geographic region, the incidence of the
      malignancy at autopsy is similar.

PMID- 23157137
TI  - [Milk fat in prophylaxis of cancer diseases].
AB  - Milk fat is characterized by extensive pro-health activity. Its unique
      components, such as: short chain saturated fatty acids, conjugated linoleic acid
      (CLA), vaccenic acid, ether lipids (alkiloglicerols and
      alkiloglicerophospholipids), 13-methyltetradecanic acid and bioactive components
      of antioxidative activity, are important in prophylaxis, and even in therapy of
      cancer diseases. Advantageous influence to maintain pro- and antioxidative
      balance of organism is revealed by the components of milk fat: conjugated
      linoleic acid, vitamins A and E, and coenzyme Q10. Moreover, vitamin D3,
      phospholipids, ether lipids, cholesterol and 13-methyltetradecanic acid also
      reveal antioxidative activity.

PMID- 23157138
TI  - [Photodynamic therapy in the treatment of breast cancer].
AB  - Breast cancer is the most common women's cancer in the world. The effective
      therapies that would not only reduce the high mortality rate associated with the
      disease, but also improve the quality of life patients with breast cancer are
      still searching for. PDT is one of the alternative method of cancers treatment,
      such as bladder, esophagus, respiratory tract and gynaecological cancers. PDT
      permit to eliminate selected cells from organism with photosensitizers and light
      use. Obtained results depend on both properties of cells as well as properties
      and localization of photosensitizer and illumination condition. In recent years
      possibilities of PDT using in breast cancer treatment are analyzed. These
      researches are focused mainly on the efficacy's assessing of different
      photosensitizers used in photodynamic therapy in vitro of different breast cancer
      cell lines, including also cells derived from metastatic lesions. The viability
      and proliferative activity of these cells, expression of selected proapoptotic
      genes, release of cytochrome c by mitochondria into the cytoplasm, the activity
      of caspases are analyzed. The first results of clinical trials were also
      described.

PMID- 23157139
TI  - [Alcohol and psychiatric disorders].
AB  - Alcohol dependence and abuse is one of the most costly health problems in the
      world from both a social and an economic point of view. It is a widespread
      problem, focusing attention not only psychiatrists but also doctors of other
      specialties. Patterns of drinking appear to be changing throughout the world,
      with more women and young people drinking heavily. Even risky drinking is a
      potential health risk, while chronic alcohol abuse contribute to the serious
      physical and mental complications. Alcohol used disorders associated with alcohol
      induced brain damage include: withdrawal state, delirium tremens, alcoholic
      hallucinosis, alcoholic paranoia, Korsakoffs psychosis, alcoholic dementia,
      alcoholic depression. On the other hand, mental disorders as panic disorder,
      social anxiety disorder, agoraphobia, depression, bipolar disorder,
      schizophrenia, personality disorder most frequently comorbid with alcohol abuse
      or they trigger alcohol.

PMID- 23157140
TI  - Hyperbaric oxygen therapy for chronic refractory osteomyelitis.

PMID- 23157143
TI  - The use of coronary computed tomography angiography to rule out CAD in the ED.

PMID- 23157144
TI  - Diagnosis of deep venous thrombosis and pulmonary embolism.
AB  - Venous thromboembolism manifests as deep venous thrombosis (DVT) or pulmonary
      embolism, and has a mortality rate of 6 to 12 percent. Well-validated clinical
      prediction rules are available to determine the pretest probability of DVT and
      pulmonary embolism. When the likelihood of DVT is low, a negative D-dimer assay
      result excludes DVT. Likewise, a low pretest probability with a negative D-dimer
      assay result excludes the diagnosis of pulmonary embolism. If the likelihood of
      DVT is intermediate to high, compression ultrasonography should be performed.
      Impedance plethysmography, contrast venography, and magnetic resonance venography
      are available to assess for DVT, but are not widely used. Pulmonary embolism is
      usually a consequence of DVT and is associated with greater mortality.
      Multidetector computed tomography angiography is the diagnostic test of choice
      when the technology is available and appropriate for the patient. It is warranted
      in patients who may have a pulmonary embolism and a positive D-dimer assay
      result, or in patients who have a high pretest probability of pulmonary embolism,
      regardless of D-dimer assay result. Ventilation-perfusion scanning is an
      acceptable alternative to computed tomography angiography in select settings.
      Pulmonary angiography is needed only when the clinical suspicion for pulmonary
      embolism remains high, even when less invasive study results are negative. In
      unstable emergent cases highly suspicious for pulmonary embolism,
      echocardiography may be used to evaluate for right ventricular dysfunction, which
      is indicative of but not diagnostic for pulmonary embolism.

PMID- 23157145
TI  - Natural family planning.
AB  - Natural family planning methods provide a unique option for committed couples.
      Advantages include the lack of medical adverse effects and the opportunity for
      participants to learn about reproduction. Modern methods of natural family
      planning involve observation of biologic markers to identify fertile days in a
      woman's reproductive cycle. The timing of intercourse can be planned to achieve
      or avoid pregnancy based on the identified fertile period. The current evidence
      for effectiveness of natural family planning methods is limited to lower-quality
      clinical trials without control groups. Nevertheless, perfect use of these
      methods is reported to be at least 95 percent effective in preventing pregnancy.
      The effectiveness of typical use is 76 percent, which demonstrates that
      motivation and commitment to the method are essential for success. Depending on
      the method, couples can learn about natural family planning methods in a single
      office visit, through online instruction, or from certified instructors.

PMID- 23157146
TI  - Diagnosis and management of gonococcal infections.
AB  - Neisseria gonorrhoeae causes urogenital, anorectal, conjunctival, and pharyngeal
      infections. Urogenital tract infections are most common. Men with gonorrhea may
      present with penile discharge and dysuria, whereas women may present with
      mucopurulent discharge or pelvic pain; however, women often are asymptomatic.
      Neonatal infections include conjunctivitis and scalp abscesses. If left
      untreated, gonorrhea may cause pelvic inflammatory disease in women, or it may
      disseminate, causing synovial and skin manifestations. Urogenital N. gonorrhoeae
      infection can be diagnosed using culture or nucleic acid amplification testing.
      Urine nucleic acid amplification tests have a sensitivity and specificity
      comparable to those of cervical and urethral samples. Fluoroquinolones are no
      longer recommended for the treatment of gonorrhea because of antimicrobial
      resistance. A single intramuscular injection of ceftriaxone, 250 mg, is first
      line treatment for uncomplicated urogenital, anorectal, or pharyngeal gonococcal
      infections. This dosage is more effective for common pharyngeal infections than
      the previously recommended dose of 125 mg. Ceftriaxone should routinely be
      accompanied by azithromycin or doxycycline to address the likelihood of
      coinfection with Chlamydia trachomatis. Azithromycin may be used as an
      alternative treatment option for patients with previous allergic reactions to
      penicillin, but because of the likelihood of antimicrobial resistance, its use
      should be limited. Gonococcal infection should prompt physicians to test for
      other sexually transmitted infections, including human immunodeficiency virus.
      Because of high reinfection rates, patients should be retested in three to six
      months. The U.S. Preventive Services Task Force recommends screening for
      gonorrhea in all sexually active women at increased risk of infection. It also
      recommends intensive behavioral counseling for persons with or at increased risk
      of contracting sexually transmitted infections. Condom use is an effective
      strategy to reduce the risk of infection.

PMID- 23157147
TI  - Revised AAP Guideline on UTI in Febrile Infants and Young Children.
AB  - In 2011, the American Academy of Pediatrics released a revision of its 1999
      clinical practice guideline on urinary tract infections in febrile infants and
      young children two to 24 months of age. The new clinical practice guideline has
      several important updates based on evidence generated over the past decade. The
      updated guideline includes clinical criteria for collecting urine specimens.
      Diagnosis now requires evidence of infection from both abnormal urinalysis
      results and positive urine culture results (the criterion for a positive culture
      has been reduced from at least 100,000 colony-forming units per mL to at least
      50,000 colony-forming units per mL). Oral treatment now is considered to be as
      effective as parenteral treatment. Renal and bladder ultrasonography is still
      recommended, but the biggest change in the current guideline is that routine
      voiding cystourethrography is no longer recommended after the first urinary tract
      infection. Follow-up is based on evaluating children for urinary tract infection
      during subsequent febrile episodes, rather than routinely performing repeat urine
      cultures.

PMID- 23157148
TI  - Screening for and management of obesity in adults.

PMID- 23157149
TI  - Widespread tender hemorrhagic patches on the breast.

PMID- 23157152
TI  - Is natural family planning a highly effective method of birth control? No:
      natural family planning methods are overrated.

PMID- 23157153
TI  - Is natural family planning a highly effective method of birth control? Yes:
      natural family planning is highly effective and fulfilling.

PMID- 23157154
TI  - Screening for and management of obesity in adults: recommendation statement.

PMID- 23157155
TI  - FPIN's clinical inquiries: infectious etiologies of acute otitis media.

PMID- 23157156
TI  - Patient education page: gonorrhea.

PMID- 23157157
TI  - Patient education page: natural family planning.

PMID- 23157158
TI  - On the polarity of buckminsterfullerene with a water molecule inside.
AB  - Since the recent achievement of Kurotobi and Murata to capture a water molecule
      in a C(60) fullerene (Science 2011, 333, 613), there has been a debate about the
      properties of this H(2)O@C(60) complex. In particular, the polarity of the
      complex, which is thought to be underlying the easy separation of H(2)O@C(60)
      from the empty fullerene by HPLC, was calculated and found to be almost equal to
      that of an isolated water molecule. Here we present our detailed analysis of the
      charge distribution of the water-encapsulated C(60) complex, which shows that the
      polarity of the complex is, with 0.5 +/- 0.1 D, indeed substantial, but
      significantly smaller than that of H(2)O. This may have important implications
      for the aim to design water-soluble and biocompatible fullerenes.

PMID- 23157159
TI  - Solar vapor generation enabled by nanoparticles.
AB  - Solar illumination of broadly absorbing metal or carbon nanoparticles dispersed
      in a liquid produces vapor without the requirement of heating the fluid volume.
      When particles are dispersed in water at ambient temperature, energy is directed
      primarily to vaporization of water into steam, with a much smaller fraction
      resulting in heating of the fluid. Sunlight-illuminated particles can also drive
      H(2)O-ethanol distillation, yielding fractions significantly richer in ethanol
      content than simple thermal distillation. These phenomena can also enable
      important compact solar applications such as sterilization of waste and surgical
      instruments in resource-poor locations.

PMID- 23157160
TI  - Derivation of the MMPI-2-RF Henry-Heilbronner Index-r (HHI-r) scale.
AB  - The 15-item Henry-Heilbronner Index (HHI) was published in 2006 as an MMPI-2
      embedded measure of psychological response validity. When the MMPI-2 was revised
      in 2008 only 11 of the 15 original HHI items were retained on the MMPI-2-RF,
      prohibiting use of the HHI as an embedded validity indicator on the MMPI-2-RF.
      Using the original HHI sample an 11-item version of the HHI, the HHI-r, was
      evaluated for use as an embedded measure of psychological response validity for
      the MMPI-2-RF. The 11-item HHI-r was very similar to the HHI in classification
      accuracy. An HHI-r cutoff score of >=7 was associated with a classification
      accuracy rate of 84.0%, good sensitivity (68.9%), and high specificity (93.2%) in
      identifying symptom exaggeration in personal injury and disability litigants
      versus non-litigating head-injured patients. These preliminary results suggest
      the HHI-r functions in a manner similar to the original HHI as a measure of
      psychological response validity, and may be used by psychologists and
      neuropsychologists as an MMPI-2-RF embedded validity indicator.

PMID- 23157161
TI  - The effect of natrium hyaluronate applied locally for pelviureteral anastomoses.
AB  - OBJECTIVES: This study aimed to investigate the effect of natrium hyaluronate
      (NH) on fibrous tissue formation and wound healing in experimental pelviureteral
      anastomosis (PUA). MATERIALS AND METHODS: Eighteen rabbits were divided equally
      into three groups: surgical (S), sham (Sh), and NH. A 1-cm length of the
      ureteropelvic segment was resected through a laparotomy incision and then
      anastomosis was performed. The rabbits were injected with saline (Sh group) and
      NH (NH group) into anastomoses lines after the surgical procedure. The S group
      did not receive any medication during their procedure. Intravenous pyelography
      was carried out on postoperative day 21. The rabbits were sacrificed and
      dissected under a dissecting microscope and examined for acute inflammation (AI),
      chronic inflammation (CI), granulation tissue amount (GTA), granulation tissue
      fibroblast maturation (GTFM), collagen deposition (CD), neovascularization (N),
      re-epithelialization (R), and peripheral tissue reaction (PTR) in the anastomosis
      lines 3 weeks later. MAIN FINDINGS: There were no significant differences in the
      GTFM scores in the S group compared with those in the NH group. In the NH group,
      N scores were higher than they were in the S group. Re-epithelialization in the
      NH group was higher than it was in the S group. PRINCIPLE CONCLUSIONS: NH did not
      decrease fibrosis, but increased important parameters in wound healing such as
      neovascularization and re-epithelialization in an experimental model of PUA in
      rabbits.

PMID- 23157162
TI  - Parental self-efficacy and oral health-related knowledge are associated with
      parent and child oral health behaviors and self-reported oral health status.
AB  - OBJECTIVES: This study sought to advance understanding of the influence of
      psychosocial factors on oral health by examining how parental self-efficacy (with
      regard to acting on their child's oral health needs) and oral health knowledge
      relate to parental and child oral health behaviors and self-rated oral health.
      METHODS: Parents of children in grades 0/1 and 5/6 (n = 804) and children in
      grades 5/6 (n = 377, mean age 11.5 +/- 1.0, 53.9% female) were recruited from a
      stratified random sample of 11 primary (elementary) schools. Participants
      completed surveys capturing psychosocial factors, oral health-related knowledge,
      and parental attitudes about oral health. Parents also rated their own oral
      health status and the oral health of their child. Correlations and logistic
      regression analysis (adjusted for socioeconomic status, child age, and gender)
      examined associations between psychosocial factors and the outcomes of interest
      (parent and child behaviors and self-rated oral health status). RESULTS: Higher
      parental self-efficacy was associated with more frequent toothbrushing (by parent
      and child), and more frequent visits to a dental professional. These associations
      were particularly strong with regard to dental visits for children, with parents
      with the highest tertile for self-efficacy 4.3 times more likely to report that
      their child attended a dentist for a checkup at least once a year (95%CI 2.52
      7.43); and 3 times more likely to report their child brushing their teeth at
      least twice a day (Adjusted Odds Ratio 3.04, 95%CI 1.64-5.64) compared with those
      parents in the lowest tertile for self-efficacy. No associations with oral health
      knowledge were found when examined by tertile of increasing knowledge.
      CONCLUSIONS: Oral health self-efficacy and knowledge are potentially modifiable
      risk factors of oral health outcomes, and these findings suggest that intervening
      on these factors could help foster positive dental health habits in families.

PMID- 23157163
TI  - Apoplastic and chloroplastic redox signaling networks in plant stress responses.
AB  - SIGNIFICANCE: Interplay among apoplastic and chloroplastic redox signaling
      networks is emerging as a key mechanism in plant stress responses. RECENT
      ADVANCES: Recent research has revealed components involved in apoplastic and
      chloroplastic redox signaling. Also, the sequence of events from stress
      perception, activation of apoplastic reactive oxygen species (ROS) burst through
      NADPH oxidases, cytoplasmic and chloroplastic Ca(2+)-transients, and organellar
      redox signals to physiological responses is starting to emerge. Moreover, a
      functional overlap between light acclimation and plant immunity in
      photosynthetically active tissues has been demonstrated. CRITICAL ISSUES: Any
      deviations from the basal cellular redox balance may induce acclimation responses
      that continuously readjust cellular functions. However, diversion of resources to
      stress responses may lead to attenuation of growth, and exaggeration of defensive
      reactions may thus be detrimental to the plant. The ultimate outcome of
      acclimation responses must therefore be tightly controlled by the redox signaling
      networks between organellar and apoplastic signaling systems. FUTURE DIRECTIONS:
      Two major questions still remain to be solved: the sensory mechanism for ROS and
      the components involved in relaying the signals from the apoplast to the
      chloroplast. A comprehensive view of regulatory networks will facilitate the
      understanding on how environmental factors affect the production of
      phytonutrients and biomass in plants. Translation of such information from model
      plants to crop species will be at the cutting edge of research in the near
      future. These challenges give a frame for future studies on ROS and redox
      regulation of stress acclimation in photosynthetic organisms.

PMID- 23157164
TI  - Antioxidant activity of phenolic acids and their metabolites: synthesis and
      antioxidant properties of the sulfate derivatives of ferulic and caffeic acids
      and of the acyl glucuronide of ferulic acid.
AB  - The main metabolites of caffeic and ferulic acids (ferulic acid-4'-O-sulfate,
      caffeic acid-4'-O-sulfate, and caffeic acid-3'-O-sulfate), the most
      representative phenolic acids in fruits and vegetables, and the acyl glucuronide
      of ferulic acid were synthesized, purified, and tested for their antioxidant
      activity in comparison with those of their parent compounds and other related
      phenolics. Both the ferric reducing antioxidant power (FRAP) assay and the 2,2'
      azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical scavenging
      method were used. Ferulic acid-4'-O-sulfate and ferulic acid-4'-O-glucuronide
      exhibited very low antioxidant activity, while the monosulfate derivatives of
      caffeic acid were 4-fold less efficient as the antioxidant than caffeic acid. The
      acyl glucuronide of ferulic acid showed strong antioxidant action. The
      antioxidant activity of caffeic acid-3'-O-glucuronide and caffeic acid-4'-O
      glucuronide was also studied. Our results demonstrate that some of the products
      of phenolic acid metabolism still retain strong antioxidant properties. Moreover,
      we first demonstrate the ex vivo synthesis of the acyl glucuronide of ferulic
      acid by mouse liver microsomes, in addition to the phenyl glucuronide.

PMID- 23157165
TI  - CAG/CTG repeats alter the affinity for the histone core and the positioning of
      DNA in the nucleosome.
AB  - Trinucleotide repeats (TNRs) occur throughout the genome, and their expansion has
      been linked to several neurodegenerative disorders, including Huntington's
      disease. TNRs have been studied using both oligonucleotides and plasmids;
      however, less is know about how repetitive DNA responds to genomic packaging.
      Here, we investigate the behavior of CAG/CTG repeats incorporated into nucleosome
      core particles, the most basic unit of chromatin packaging. To assess the general
      interaction between CAG/CTG repeats and the histone core, we determined the
      efficiency with which various TNR-containing DNA substrates form nucleosomes,
      revealing that even short CAG/CTG tracts are robust incorporators. However, the
      presence of the Huntington gene flanking sequence (htt) decreases the rate of
      incorporation. Enzymatic and chemical probing revealed repositioning of the DNA
      in the nucleosome as the number of CAG/CTG repeats increased, regardless of the
      flanking sequence. Notably, the periodicity of the repeat tract remained
      unchanged as a function of length and is consistently 10.7 bp per helical turn.
      In contrast, the periodicity of the nonrepetitive flanking sequence varies and is
      smaller than the repeat tract at ~10.0-10.5 bp per turn. Furthermore, while the
      CAG/CTG repeats remain as a canonical duplex in the nucleosome, nucleosome
      formation causes kinking in a secondary repeat tract in the htt gene, comprised
      of CCG/CGG repeats. This work highlights the innate ability of CAG/CTG repeats to
      incorporate and to position in nucleosomes and how that behavior is modulated by
      the htt flanking sequence. In addition, it illuminates the differences in
      packaging of healthy and diseased length repeat tracts within the genome.

PMID- 23157167
TI  - Molecular germanium selenophosphate salts: phase-change properties and strong
      second harmonic generation.
AB  - A new series of germanium chalcophosphates with the formula A(4)GeP(4)Q(12) (A =
      K, Rb, Cs; Q = S, Se) have been synthesized. The selenium compounds are
      isostructural and crystallize in the polar orthorhombic space group Pca2(1). The
      sulfur analogues are isostructural to one another but crystallize in the
      centrosymmetric monoclinic space group C2/c. All structures contain the new
      molecular anion [GeP(4)Q(12)](4-); however, the difference between the sulfides
      and selenides arises from the change in crystal packing. Each discrete molecule
      is comprised of two ethane-like P(2)Q(6) units that chelate to a central
      tetrahedral Ge(4+) ion in a bidentate fashion. The selenides were synthesized
      pure by stoichiometric reaction of the starting materials, whereas the sulfides
      contained second phases. The band gaps of the molecular salts are independent of
      the alkali metal counterions and have a value of 2.0 eV for the selenides and 3.0
      3.1 eV for the sulfides. All A(4)GeP(4)Se(12) compounds melt congruently, and the
      potassium analogue can be quenched to give a glassy phase that retains its short
      range order as shown by Raman spectroscopy and powder X-ray diffraction.
      Interestingly, K(4)GeP(4)Se(12) is a phase-change material that reversibly
      converts between glassy and crystalline states and passes through a metastable
      crystalline state upon heating just before crystallizing into its slow-cooled
      form. Initial second harmonic generation (SHG) experiments showed crystalline
      K(4)GeP(4)Se(12) outperforms the other alkali metal analogues and exhibits the
      strongest second harmonic generation response among reported quaternary
      chalcophosphates, ~30 times that of AgGaSe(2) at 730 nm. A more thorough
      investigation of the nonlinear optical (NLO) properties was performed across a
      range of wavelengths that is almost triple that of previous reports (lambda =
      1200-2700 nm) and highlights the importance of broadband measurements. Glassy
      K(4)GeP(4)Se(12) also exhibits a measurable SHG response with no poling.

PMID- 23157166
TI  - Influence of chronic amphetamine treatment and acute withdrawal on serotonin
      synthesis and clearance mechanisms in the rat ventral hippocampus.
AB  - Amphetamine withdrawal in both humans and rats is associated with increased
      anxiety states, which are thought to contribute to drug relapse. Serotonin in the
      ventral hippocampus mediates affective behaviors, and reduced serotonin levels in
      this region are observed in rat models of high anxiety, including during
      withdrawal from chronic amphetamine. This goal of this study was to understand
      the mechanisms by which reduced ventral hippocampus serotonergic
      neurotransmission occurs during amphetamine withdrawal. Serotonin synthesis
      (assessed by accumulation of serotonin precursor as a measure of the capacity of
      in vivo tryptophan hydroxylase activity), expression of serotonergic
      transporters, and in vivo serotonergic clearance using in vivo microdialysis were
      assessed in the ventral hippocampus in adult male Sprague Dawley rats at 24 h
      withdrawal from chronic amphetamine. Overall, results showed that diminished
      extracellular serotonin at 24 h withdrawal from chronic amphetamine was not
      accompanied by a change in capacity for serotonin synthesis (in vivo tryptophan
      hydroxylase activity), or serotonin transporter expression or function in the
      ventral hippocampus, but instead was associated with increased expression and
      function of organic cation transporters (low-affinity, high-capacity serotonin
      transporters). These findings suggest that 24 h withdrawal from chronic
      amphetamine reduces the availability of extracellular serotonin in the ventral
      hippocampus by increasing organic cation transporter-mediated serotonin
      clearance, which may represent a future pharmacological target for reversing
      anxiety states during drug withdrawal.

PMID- 23157168
TI  - Discovery of cell compartment specific protein-protein interactions using
      affinity purification combined with tandem mass spectrometry.
AB  - Affinity purification combined with tandem mass spectrometry (AP-MS/MS) is a well
      established method used to discover interaction partners for a given protein of
      interest. Because most AP-MS/MS approaches are performed using the soluble
      fraction of whole cell extracts (WCE), information about the cellular
      compartments where the interactions occur is lost. More importantly, classical AP
      MS/MS often fails to identify interactions that take place in the nonsoluble
      fraction of the cell, for example, on the chromatin or membranes; consequently,
      protein complexes that are less soluble are underrepresented. In this paper, we
      introduce a method called multiple cell compartment AP-MS/MS (MCC-AP-MS/MS),
      which identifies the interactions of a protein independently in three fractions
      of the cell: the cytoplasm, the nucleoplasm, and the chromatin. We show that this
      fractionation improves the sensitivity of the method when compared to the
      classical affinity purification procedure using soluble WCE while keeping a very
      high specificity. Using three proteins known to localize in various cell
      compartments as baits, the CDK9 subunit of transcription elongation factor P
      TEFb, the RNA polymerase II (RNAP II)-associated protein 4 (RPAP4), and the
      largest subunit of RNAP II, POLR2A, we show that MCC-AP-MS/MS reproducibly yields
      fraction-specific interactions. Finally, we demonstrate that this improvement in
      sensitivity leads to the discovery of novel interactions of RNAP II carboxyl
      terminal domain (CTD) interacting domain (CID) proteins with POLR2A.

PMID- 23157169
TI  - Snail promotes an invasive phenotype in lung carcinoma.
AB  - BACKGROUND: Snail is a transcriptional factor which is known to influence the
      epitheliomesenchymal transition (EMT) by regulating adhesion proteins such as E
      cadherin and claudins as well as matrix metalloproteases (MMP). METHODS: To
      evaluate the functional importance of snail, a transciptional factor involved in
      EMT in lung tumors, we investigated its expression in a large set of lung
      carcinomas by immunohistochemistry. Expression of snail and effects of snail
      knockdown was studied in cell lines. RESULTS: Nuclear snail expression was seen
      in 21% of cases this being strongest in small cell lung carcinomas (SCLC). There
      was significantly greater snail expression in SCLC compared to squamous cell or
      adenocarcinoma. Positive snail expression was associated with poor survival in
      the whole material and separately in squamous cell and adenocarcinomas. In Cox
      regression analysis, snail expression showed an independent prognostic value in
      all of these groups. In several cell lines knockdown of snail reduced invasion in
      both matrigel assay and in the myoma tissue model for invasion. The influence of
      snail knockdown on claudin expression was cell type specific. Snail knockdown in
      these cell lines modified the expression of MMP2 and MMP9 but did not influence
      the activation of these MMPs to any significant degree. CONCLUSIONS: The results
      show that snail plays an important role in the invasive characteristics of lung
      carcinoma influencing the survival of the patients. Snail knockdown might thus be
      one option for targeted molecular therapy in lung cancer. Snail knockdown
      influenced the expression of claudins individually in a cell-line dependent
      manner but did not influence MMP expressions or activations to any significant
      degree.

PMID- 23157170
TI  - Thyroid hemiagenesis, ectopic submandibular thyroid tissue, and apparent
      persistent subclinical thyrotoxicosis.
AB  - BACKGROUND: Ectopic thyroid tissue (ETT) is a rare embryological abnormality
      characterized by the occurrence of thyroid tissue in a site other than its usual
      location. Thyroid hemiagenesis (HA) is also a very rare abnormality in which one
      thyroid lobe does not develop properly during embryology. We report a patient
      with left HA, submandibular ETT, and persistent mildly suppressed serum
      thyrotropin (TSH). PATIENT: A 38-year-old female patient was admitted with
      complaints of sweating and palpitations. She had no symptoms of neck compression.
      Thyroid ultrasonography revealed heterogeneity and hypoechogenicity of the right
      lobe and absence of the left lobe, the latter being confirmed by computed
      tomography. There was no ETT in the neck. A thyroid Tc-99m pertechnetate scan
      demonstrated two distinct areas of radiotracer uptake, one in the right lobe of
      the thyroid gland and one in the right submandibular region and lobe, but no
      uptake in the left thyroid bed. The serum free triiodothyronine was 2.89 pg/mL
      (2.5-3.9 pg/mL), and the serum free thyroxine was 0.86 ng/dL (0.61-1.12 ng/mL).
      The serum TSH was 0.11 mIU/L (0.34-5.60 mIU/L). CONCLUSIONS: This may be the
      first reported patient with HA and submandibular ETT. The patient probably also
      had thyroiditis with mild intermittent thyrotoxicosis based on her suppressed TSH
      and ultrasonography imaging of the right thyroid lobe.

PMID- 23157171
TI  - Characterizing the transition from paediatric to adult care among emerging adults
      with Type 1 diabetes.
AB  - AIMS: The goals of the study were to describe the transition of youth with Type 1
      diabetes from paediatric to adult healthcare services, examine the link of this
      transition with self care and glycaemic control, and distinguish youth who
      received medical treatment from different physicians in terms of demographic and
      parent relationship variables. METHODS: Youth with Type 1 diabetes (n = 118) were
      enrolled in a prospective study that examined the transition from the paediatric
      to adult healthcare systems and were evaluated during their senior year of high
      school (time 1) and 1 year later (time 2). Data on self care, glycaemic control
      and parent relationship were collected. RESULTS: The majority of youth saw a
      paediatric endocrinologist at both assessments (n = 64); others saw an adult care
      physician at both assessments (n = 26) or transitioned from a paediatric
      endocrinologist to an adult care physician (n = 19). Nine youth saw no physician
      between time 1 and time 2. There were group differences in demographic and parent
      relationship variables and self-care behaviour and glycaemic control related to
      the transition of care. Youth who remained in the paediatric healthcare system
      had the best self care and did not experience declines in glycaemic control over
      time. CONCLUSIONS: Early transition from the paediatric healthcare system to the
      adult healthcare system is associated with psychosocial variables and worse
      glycaemic control. Future research should identify factors that determine optimal
      timing and strategies to avoid deterioration of care and control during this
      transition.

PMID- 23157172
TI  - Salt chamber treatment is ineffective in treating eosinophilic inflammation in
      asthma.
AB  - BACKGROUND: We have shown that salt chamber treatment reduces airway hyper
      responsiveness as an add-on therapy in adult asthmatics on inhaled
      corticosteroids. METHODS: We assessed whether this effect is due to the
      suppression of eosinophilic airway inflammation. Thirty-nine adult asthmatics on
      inhaled corticosteroids were randomized to receive active salt chamber treatment
      with low-salt treatment 6.6 mg/m(3)  (n = 14), high-salt treatment 10.8 mg/m(3) 
      (n = 15) or placebo 0.3 mg/m(3)  (n = 10) 10 times in a 2 weeks' period in a
      double-blind manner. RESULTS: The level of induced sputum eosinophilic cationic
      protein MUg/l, was 3070 before and 4651 after the low-salt treatment period, on
      average. In the high-salt treatment group, it was 12 192 MUg/l vs 11 803 and in
      the placebo group 3942 vs 4144, respectively. Salt chamber treatment had no
      effect on sputum eosinophil or neutrophil cell numbers. CONCLUSIONS: The
      reduction in hyper-responsiveness observed in the previous study is probably not
      due to the effect on eosinophilic inflammation.

PMID- 23157173
TI  - The myogenic mechanism of synchronization and coordination for uterine myocytes
      contractions during labor.
AB  - The article summarized the results of many years studying of synchronization and
      coordination of uterine myocytes contractile activity during physiological labor
      contractions. The authors suggest that the physiological basis for these
      processes is the mechanoreceptor mechanism of feedback for the stretching which
      is one of the fundamental mechanisms for control contractile activity of uterine
      myocytes during parturition.

PMID- 23157174
TI  - Monomeric group 13 metal(I) amides: enforcing one-coordination through extreme
      ligand steric bulk.
AB  - Reactions of the extremely bulky amido alkali metal complexes, [KL'(eta(6)
      toluene)], or in situ generated [LiL'] or [LiL"] {L'/ L" = N(Ar*)(SiR(3)), where
      Ar* = C(6)H(2){C(H)Ph(2)}(2)Me-2,6,4 and R = Me (L') or Ph (L")} with group 13
      metal(I) halides have yielded a series of monomeric metal(I) amide complexes,
      [ML'] (M = Ga, In, or Tl) and [ML"] (M = Ga or Tl), all but one of which have
      been crystallographically characterized. The results of the crystallographic
      studies, in combination with computational analyses, reveal that the metal
      centers in these compounds are one coordinate and do not exhibit any significant
      intra- or intermolecular interactions, other than their N-M linkages. One of the
      complexes, [InL'], represents the first example of a one-coordinate indium(I)
      amide. Attempts to extend this study to the preparation of the analogous
      aluminum(I) amide, [AlL'], were not successful. Despite this, a range of novel
      and potentially synthetically useful aluminum(III) halide and hydride complexes
      were prepared en route to [AlL'], the majority of which were crystallographically
      characterized. These include the alkali metal aluminate complexes, [L'AlH(2)(MU
      H)Li(OEt(2))(2)(THF)] and [{L'Al(MU-H)(3)K}(2)], the neutral amido-aluminum
      hydride complex, [{L'AlH(MU-H)}(2)], and the aluminum halide complexes,
      [L'AlBr(2)(THF)] and [L'AlI(2)]. Reaction of the latter two systems with a
      variety of reducing agents led only to intractable product mixtures.

PMID- 23157175
TI  - The transcriptional control machinery as well as the cell wall integrity and its
      regulation are involved in the detoxification of the organic solvent dimethyl
      sulfoxide in Saccharomyces cerevisiae.
AB  - In the present study, we have identified 339 dimethyl sulfoxide (DMSO)-sensitive
      and nine DMSO-tolerant gene mutations in Saccharomyces cerevisiae through a
      functional genomics approach. Twelve of these identified DMSO-sensitive mutations
      are of genes involved in the general control of gene expression mediated by the
      SWR1 complex and the RNA polymerase II mediator complex, whereas 71 of them are
      of genes involved in the protein trafficking and vacuolar sorting processes. In
      addition, twelve of these DMSO-sensitive mutations are of genes involved in the
      cell wall integrity (CWI) and its regulation. DMSO-tolerant mutations are of
      genes mainly involved in the metabolism and the gene expression control.
      Therefore, the transcriptional control machinery, the CWI and its regulation as
      well as the protein trafficking and sorting process play critical roles in the
      DMSO detoxification in yeast cells.

PMID- 23157177
TI  - Synthesis of octopus-tentacle-like Cu nanowire-Ag nanocrystals heterostructures
      and their enhanced electrocatalytic performance for oxygen reduction reaction.
AB  - In this article, the novel octopus-tentacle-like Cu nanowire-Ag nanocrystals
      heterostructures have been fabricated in solution phase via heterogeneous
      nucleation and growth of Ag nanocrystals on presynthesized Cu nanowires. The
      growth environment and dynamic factors of Ag nanocrystals play an important role
      for formation of such heterostructures. Combined the physical constants of Cu and
      Ag with a series of control experiments, the epitaxial growth means of Ag
      nanocrystals on Cu nanowire is found to abide by "layer-plus-island" (Stranski
      Krastanow) mode. Because of the presence of multiple junctions and strong
      synergistic effect of their constituents, the obtained heterostructures exhibit
      greatly enhanced electrocatalytic performance toward oxygen reduction reaction
      compared with that of pure Ag nanocrystals, Cu nanowires, and mechanically mixed
      dual components as well as recently reported some non-Pt materials, which can be
      served as an alternative cathodic electrocatalyst to apply in alkaline fuel
      cells. Moreover, our method can be extended to fabricate octopus-tentacle-like Cu
      nanowire-Au nanocrystals and Cu nanowire-Pd nanocrystals heterostructures.

PMID- 23157176
TI  - Surgical cyst decortication in autosomal dominant polycystic kidney disease.
AB  - PURPOSE: To provide a summary of the relevant literature regarding the impact of
      surgical cyst decortication on hypertension, renal function, and pain management
      in patients with autosomal dominant polycystic kidney disease (ADPKD). METHODS:
      Data collection was conducted via a Medline search using the subject headings
      autosomal dominant polycystic kidney disease, surgery, decortication, and
      marsupialization. Additional reports were derived from references included within
      these articles. RESULTS: Despite a trend for improved blood pressure control
      after cyst decortication in some studies, this cumulative review of the
      literature did not provide consistent evidence supporting the role of this
      procedure in blood pressure management in patients with ADPKD. Surgical cyst
      decortication was associated with renal deterioration in a subset of patients
      with compromised baseline renal function but did not otherwise appear to have a
      significant impact on renal function in the majority of studies reviewed.
      Improvement in chronic pain after this procedure was ubiquitously reported across
      all studies examined. CONCLUSIONS: Despite a potential role in blood pressure
      management in the setting of ADPKD, surgical cyst decortication has not been
      definitively shown to alleviate hypertension in this clinical setting. Renal
      function does not appear to improve following this surgery. Patients with
      compromised baseline renal function appear to be at increased risk for further
      deterioration in renal function after cyst decortication, although the role of
      this procedure in altering the natural trajectory of renal failure in this
      patient subset needs further investigation. Cyst decortication is highly
      effective in the management of disease-related chronic pain for the majority of
      patients with ADPKD, providing durable pain relief in this patient population.

PMID- 23157178
TI  - Therapeutic potential of amniotic fluid stem cells.
AB  - Human amniotic fluid cells have been used traditionally as a diagnostic tool for
      genetic anomalies. More recently it has been recognized that amniotic fluid
      contains populations of stem cells. Mesenchymal stem cells (AFMSC) were first to
      be described. These cells are able to differentiate towards mesodermal lineages.
      More recently cells with broader potential, defined as amniotic fluid stem cells
      (AFSC), were also isolated. They have intermediate characteristics between
      embryonic and adult stem cells and are able to differentiate into lineages
      representative of all three germ layers but unlike ES cells they do not form
      tumours in vivo. Furthermore, AFSC have been reverted to functional pluripotency
      in a transgene-free approach using an epigenetics modifier. These
      characteristics, together with absence of ethical issues concerning their
      employment, have made stem cells from amniotic fluid a promising candidate for
      cell therapy and tissue engineering.

PMID- 23157179
TI  - Surfactant therapy of pulmonary conditions excluding those with primary
      surfactant deficiency and bronchoscopy as delivery method: an overview of Russian
      patents and publications.
AB  - Preparations of pulmonary surfactant are used for the treatment of respiratory
      distress syndrome in a newborn. Their applicability as a method of routine for
      lung diseases beyond the neonatal period is questionable. Some publications from
      the former Soviet Union (SU) have reported on successful surfactant therapy of
      ARDS in children and adults as well as for inhalation injuries, pneumonia, and
      tuberculosis. Bronchoscopy was used and recommended as a method of surfactant
      delivery for ARDS, some types of pneumonia and tuberculosis. Manufacturing
      processes of surfactant preparations from bovine lung and amniotic fluid,
      described by Russian patents, and bronchoscopy as a delivery mode are discussed
      here. A concluding point is that some reports from the former SU about
      administration of exogenous surfactant in pulmonary conditions, excluding those
      with primary surfactant deficiency, are only partly confirmed by the
      international literature.

PMID- 23157180
TI  - Numerical simulation of a susceptible-exposed-infectious space-continuous model
      for the spread of rabies in raccoons across a realistic landscape.
AB  - We introduce a numerical model for the spread of a lethal infectious disease in
      wildlife. The reference model is a Susceptible-Exposed-Infectious system where
      the spatial component of the dynamics is modelled by a diffusion process. The
      goal is to develop a model to be used for real geographical scenarios, so we do
      not rely upon simplifying assumptions on the shape of the region of interest. For
      this reason, space discretization is carried out with the finite element method
      on an unstructured triangulation. A diffusion term is designed to take into
      account landscape heterogeneities such as mountains and waterways. Numerical
      simulations are carried out for rabies epidemics among raccoons in New York
      state. A qualitative comparison of numerical results to available data from real
      world epidemics is discussed. 

PMID- 23157181
TI  - Vacuum-assisted closure for complex cranial wounds involving the loss of dura
      mater.
AB  - The aim in this study was to describe the safety and efficacy of vacuum-assisted
      closure (VAC) in patients with complex cranial wounds with extensive scalp, bone,
      and dural defects who were not candidates for immediate free tissue transfer.
      Five patients (4 men and 1 woman) ages 24-73 years with complex cranial wounds
      were treated with VAC at Wake Forest Baptist Medical Center. Etiologies included
      trauma, squamous cell carcinoma, and malignant meningioma. Cutaneous wound
      defects measured as large as 15 cm in diameter. Four of the 5 patients had open
      skull defects with concomitant dural defects, and 1 patient had dural dehiscence.
      After surgical debridement, all 5 patients were treated with the direct
      application of a VAC device to a reapproximated dura mater (1 patient), to a
      pericranial flap (1 patient), or to a regenerative tissue matrix overlying CNS
      tissue (3 patients). In all cases involving open cranial wounds, the VAC device
      promoted granulation tissue formation over the dural substitute, prevented CSF
      leakage, and kept the wounds free from local infection. The duration of VAC
      therapy ranged from 16 to 91 days. Although VAC therapy was intended as a
      temporary measure until these patients could be stabilized for larger tissue
      transfer procedures or they succumbed to their primary pathology, 1 patient had a
      successful skin graft following VAC therapy. Hydrocephalus requiring shunt
      placement developed in 2 patients during VAC therapy. The VAC dressings applied
      to a tissue matrix or other barrier over brain tissue in extensive cranial wounds
      are safe and well tolerated, providing a functional barrier and preventing
      infection.

PMID- 23157182
TI  - The inferior medullary velum: anatomical study and neurosurgical relevance.
AB  - OBJECT: Although it is often visualized surgically, details regarding the
      inferior medullary velum are lacking in the literature. The present study is
      intended to better elucidate this neuroanatomical structure using microsurgical
      and immunohistochemical analyses. METHODS: To study the inferior medullary velum,
      the authors performed microdissection in 15 adult cadavers. Following gross
      study, specimens were examined histologically. RESULTS: The inferior medullary
      velum extended from the flocculus to the middle cerebellar peduncle and stretched
      between the inferior cerebellar peduncle and the nodule and pyramid. The average
      thickness of the velum was found to be 0.5 mm (range 0.35-0.8 mm) and the average
      length was found to be 6 mm (range 5.5-7.2 mm). Arterial branches were identified
      in all specimens that arose from medullary branches of the posterior inferior
      cerebellar artery and supplied the inferior medullary velum. Histologically and
      from internal to external, a choroid plexus epithelium as a single cell layer was
      adjacent to a cuboidal layer of ependymal cells with no visible cilia. The next
      layer contained scattered glia in single cells or small clusters. The most
      external layer was composed of flat spindle cells resembling fibroblasts. No
      neurons of any type were identified. Only rare axons traversed the thin
      hypocellular zone that disappeared toward the midline. CONCLUSIONS: Based on this
      cadaveric study, the authors conclude that division of the inferior medullary
      velum should be relatively harmless as no neuronal cells were identified in this
      structure, which appears to be a vestigial bridge of tissue between the left and
      right sides of the cerebellum.

PMID- 23157183
TI  - Pneumonia in patients with severe head injury: incidence, risk factors, and
      outcomes.
AB  - OBJECT: The reported incidence of hospital-acquired bacterial pneumonia in
      critically ill trauma patients varies from as low as 4% to as high as 87%, with
      fatality rates varying from 6% to 59%. Clinical studies have identified the risk
      factors for pneumonia. The authors undertook this retrospective study to evaluate
      the incidence, risk factors, and outcomes of hospital-acquired bacterial
      pneumonia in a group of patients with severe head injuries. METHODS: This was a
      retrospective review of consecutive adult patients admitted to the neurosurgical
      ICU in the authors' hospital because of severe head injury (Glasgow Coma Scale
      scores <= 8) between January 2008 and December 2010. RESULTS: During the study
      period, 290 patients were admitted to the neurosurgical ICU. Multivariate Cox
      regression analysis showed that age (HR 1.01, 95% CI 1.001-1.02), nasogastric
      tube insertion (HR 4.56, 95% CI 1.11-18.64), and hemiplegia or hemiparesis (HR
      3.79, 95% CI 2.01-7.17) were significantly associated with the development of
      pneumonia. CONCLUSIONS: The authors identified 3 risk factors (age, nasogastric
      tube insertion, and hemiplegia or hemiparesis) associated with the development of
      pneumonia in patients with severe head injury. This finding constituted the basis
      for developing a simple screening tool that can be used to assess the risk of
      occurrence of pneumonia in such patients.

PMID- 23157184
TI  - Comparing indocyanine green videoangiography to the gold standard of
      intraoperative digital subtraction angiography used in aneurysm surgery.
AB  - OBJECT: The purpose of aneurysm surgery is complete aneurysm obliteration while
      sparing associated arteries. Indocyanine green (ICG) videoangiography is a new
      technique that allows for real-time evaluation of blood flow in the aneurysm and
      vessels. The authors performed a retrospective study to compare the accuracy of
      ICG videoangiography with intraoperative angiography (IA), and determine if ICG
      videoangiography can be used without follow-up IA. METHODS: From June 2007
      through September 2009, 155 patients underwent craniotomies for clipping of
      aneurysms. Operative summaries, angiograms, and operative and ICG
      videoangiography videos were reviewed. The number, size, and location of
      aneurysms, the ICG videoangiography and IA findings, and the need for clip
      adjustment after ICG videoangiography and IA were recorded. Discordance between
      ICG videoangiography and IA was defined as ICG videoangiography demonstrating
      aneurysm obliteration and normal vessel flow, but post-IA showing either an
      aneurysmal remnant and/or vessel occlusion requiring clip adjustment. RESULTS:
      Thirty-two percent of patients (49 of 155) underwent both ICG videoangiography
      and IA. The post-ICG videoangiography clip adjustment rate was 4.1% (2 of 49).
      The overall rate of ICG videoangiography-IA agreement was 75.5% (37 of 49) and
      the ICG videoangiography-IA discordance rate requiring post-IA clip adjustment
      was 14.3% (7 of 49). Adjustments were due to 3 aneurysmal remnants and 4 vessel
      occlusions. These adjustments were attributed to obscuration of the residual
      aneurysm or the affected vessel from the field of view and the presence of dye in
      the affected vessel via collateral flow. Although not statistically significant,
      there was a trend for ICG videoangiography-IA discordance requiring clip
      adjustment to occur in cases involving the anterior communicating artery complex,
      with an odds ratio of 3.3 for ICG videoangiography-IA discordance in these cases.
      CONCLUSIONS: These results suggest that care should be taken when considering ICG
      videoangiography as the sole means for intraoperative evaluation of aneurysm clip
      application. The authors further conclude that IA should remain the gold standard
      for evaluation during aneurysm surgery. However, a combination of ICG
      videoangiography and IA may ultimately prove to be the most effective strategy
      for maximizing the safety and efficacy of aneurysm surgery.

PMID- 23157185
TI  - Transcranial magnetic resonance-guided focused ultrasound surgery for trigeminal
      neuralgia: a cadaveric and laboratory feasibility study.
AB  - OBJECT: Transcranial MR-guided focused ultrasound surgery (MRgFUS) is evolving as
      a treatment modality in neurosurgery. Until now, the trigeminal nerve was
      believed to be beyond the treatment envelope of existing high-frequency
      transcranial MRgFUS systems. In this study, the authors explore the feasibility
      of targeting the trigeminal nerve in a cadaveric model with temperature
      assessments using computer simulations and an in vitro skull phantom model fitted
      with thermocouples. METHODS: Six trigeminal nerves from 4 unpreserved cadavers
      were targeted in the first experiment. Preprocedural CT scanning of the head was
      performed to allow for a skull correction algorithm. Three-Tesla, volumetric,
      FIESTA MRI sequences were performed to delineate the trigeminal nerve and any
      vascular structures of the cisternal segment. The cadaver was positioned in a
      focused ultrasound transducer (650-kHz system, ExAblate Neuro, InSightec) so that
      the focus of the transducer was centered at the proximal trigeminal nerve,
      allowing for targeting of the root entry zone (REZ) and the cisternal segment.
      Real-time, 2D thermometry was performed during the 10- to 30-second sonication
      procedures. Post hoc MR thermometry was performed on a computer workstation at
      the conclusion of the procedure to analyze temperature effects at neuroanatomical
      areas of interest. Finally, the region of the trigeminal nerve was targeted in a
      gel phantom encased within a human cranium, and temperature changes in regions of
      interest in the skull base were measured using thermocouples. RESULTS: The
      trigeminal nerves were clearly identified in all cadavers for accurate targeting.
      Sequential sonications of 25-1500 W for 10-30 seconds were successfully performed
      along the length of the trigeminal nerve starting at the REZ. Real-time MR
      thermometry confirmed the temperature increase as a narrow focus of heating by a
      mean of 10 degrees C. Postprocedural thermometry calculations and thermocouple
      experiments in a phantom skull were performed and confirmed minimal heating of
      adjacent structures including the skull base, cranial nerves, and cerebral
      vessels. For targeting, inclusion of no-pass regions through the petrous bone
      decreased collateral heating in the internal acoustic canal from 16.7 degrees C
      without blocking to 5.7 degrees C with blocking. Temperature at the REZ target
      decreased by 3.7 degrees C with blocking. Similarly, for midcisternal targeting,
      collateral heating at the internal acoustic canal was improved from a 16.3
      degrees C increase to a 4.9 degrees C increase. Blocking decreased the target
      temperature increase by 4.4 degrees C for the same power settings. CONCLUSIONS:
      This study demonstrates focal heating of up to 18 degrees C in a cadaveric
      trigeminal nerve at the REZ and along the cisternal segment with transcranial
      MRgFUS. Significant heating of the skull base and surrounding neural structures
      did not occur with implementation of no-pass regions. However, in vivo studies
      are necessary to confirm the safety and efficacy of this potentially new,
      noninvasive treatment.

PMID- 23157186
TI  - Editorial: indocyanine green videoangiography or intraoperative angiography?

PMID- 23157188
TI  - The assessment of performance and self-report validity in persons claiming pain
      related disability.
AB  - One third of all people will experience spinal pain in their lifetime and half of
      these will experience chronic pain. Pain often occurs in the context of a legally
      compensable event with back pain being the most common reason for filing a
      Workers Compensation claim in the United States. When financial incentives to
      appear disabled exist, malingered pain-related disability is a potential problem.
      Malingering may take the form of exaggerated physical, emotional, or cognitive
      symptoms and/or under-performance on measures of cognitive and physical capacity.
      Essential to the accurate detection of Malingered Pain-related Disability is the
      understanding that malingering is an act of will, the goal of which is to
      increase the appearance of disability beyond that which would naturally arise
      from the injury in question. This paper will review a number of Symptom Validity
      Tests (SVTs) that have been developed to detect malingering in patients claiming
      pain-related disability and will conclude with a review of studies showing the
      diagnostic benefit of combining SVT findings from a comprehensive malingering
      assessment. The utilization of a variety of tools sensitive to the multiple
      manifestations of malingering increases the odds of detecting invalid claims
      while reducing the risk of rejecting a valid claim.

PMID- 23157189
TI  - A novel method to measure the mechanical pushing and pulling forces during
      ureteroscopy in a normal clinical setting.
AB  - BACKGROUND AND PURPOSE: The forces needed to move the ureteroscope up and down
      the urinary tract may injure the ureter, but a method to measure these forces in
      patients is lacking. The purpose of the study was to develop and test a novel
      method for measuring the pushing and pulling forces exerted on a semirigid
      ureteroscope during ureteroscopy (URS) in a clinical setting. MATERIALS AND
      METHODS: During 2010 to 2011, 20 patients planned for retrograde flexible URS or
      percutaneous lithotripsy for renal pelvic stones were recruited to a study
      measuring the forces exerted on a semirigid ureteroscope during retrograde URS. A
      coupling device was constructed to connect a digital force meter to a standard
      semirigid ureteroscope. The pushing and pulling forces, given in Newton (N), were
      measured at four defined locations in the ureter. The experiment was repeated
      twice to evaluate the reproducibility of the results. Paired-samples t test and
      Intraclass Correlation Coefficient (ICC) addressed the reproducibility of the
      results. RESULTS: The force meter did not disturb the endoscopic procedure, and
      the force measurements were performed as intended. The results were reproducible
      at repeated measurements, with the ICC ranging from minimum 0.737 to maximum
      0.812 at the different measuring locations in the ureter. The mean forces needed
      for insertion of the ureteroscope increased from 4.4 N (+/-3.6 N) at the distal
      part of the ureter to 9.7 N (+/-7.3 N) at the proximal part with large
      interpatient variation. Similar but smaller forces were found for retraction.
      CONCLUSION: The present method is proven to reliably measure forces exerted on
      the ureteroscope in a clinical setting. This opens the opportunity for further
      force studies on endoscopic procedures to make URS safer.

PMID- 23157187
TI  - S-nitrosylation: specificity, occupancy, and interaction with other post
      translational modifications.
AB  - SIGNIFICANCE: S-nitrosylation (SNO) has been identified throughout the body as an
      important signaling modification both in physiology and a variety of diseases.
      SNO is a multifaceted post-translational modification, in that it can either act
      as a signaling molecule itself or as an intermediate to other modifications.
      RECENT ADVANCES AND CRITICAL ISSUES: Through extensive SNO research, we have made
      progress toward understanding the importance of single cysteine-SNO sites;
      however, we are just beginning to explore the importance of specific SNO within
      the context of other SNO sites and post-translational modifications.
      Additionally, compartmentalization and SNO occupancy may play an important role
      in the consequences of the SNO modification. FUTURE DIRECTIONS: In this review,
      we will consider the context of SNO signaling and discuss how the transient
      nature of SNO, its role as an oxidative intermediate, and the pattern of SNO,
      should be considered when determining the impact of SNO signaling.

PMID- 23157190
TI  - Saturated, omega-6 and omega-3 dietary fatty acid effects on the characteristics
      of fresh, frozen-thawed semen and blood parameters in rams.
AB  - The aim of this study was to investigate the effects of several dietary fatty
      acids (FAs) on semen quality and blood parameters in rams. We gave diet
      supplemented treatments (35 g day(-1) ram(-1)) by C16:0 (palm oil), C18:2
      [sunflower oil (SO)] and an n-3 source [fish oil (FO)] to 12 rams, who were fed
      for 15 weeks during their breeding season. Semen was collected once per week.
      Semen samples were extended with Tris-based cryoprotective diluents, then cooled
      to 5  degrees C and stored in liquid nitrogen. Positive responses were seen with
      FO after 4 weeks. The mean prefreezing semen characteristics improved with the
      intake of FO (P < 0.05). Interestingly, maximum sperm output in FO was achieved
      7.5 * 10(9) when compared to palm oil 5.3 * 10(9). Rams that received FO had the
      highest total testosterone concentrations (11.3 ng ml(-1) for FO, 10.8 ng ml(-1)
      for SO and 10.2 ng ml(-1) for palm oil) during the experiment (P < 0.05). FO also
      improved the rams' sperm characteristics after thawing (P < 0.05). Although C16:0
      is a major saturated FA in ram sperm and all rams have been fed isoenergetic
      rations, the unique FAs of FO improved fresh semen quality and freezing ability
      compared to other oils.

PMID- 23157191
TI  - Asthma severity in childhood and metabolomic profiling of breath condensate.
AB  - BACKGROUND: Asthma is a heterogeneous disease and its different phenotypes need
      to be better characterized from a biochemical-inflammatory standpoint. This study
      aimed to apply the metabolomic approach to exhaled breath condensate
      (breathomics) to discriminate different asthma phenotypes, with a particular
      focus on severe asthma in children. METHODS: In this cross-sectional study, we
      recruited 42 asthmatic children (age, 8-17 years): 31 with nonsevere asthma
      (treated with inhaled steroids or not) and 11 with severe asthma. Fifteen healthy
      children were enrolled as controls. Children performed exhaled nitric oxide
      measurement, spirometry, exhaled breath condensate (EBC) collection. Condensate
      samples were analyzed using a metabolomic approach based on mass spectrometry.
      RESULTS: A robust Bidirectional-Orthogonal Projections to Latent Structures
      Discriminant Analysis (O2PLS-DA) model was found for discriminating both between
      severe asthma cases and healthy controls (R(2)  = 0.93; Q(2)  = 0.75) and between
      severe asthma and nonsevere asthma (R(2)  = 0.84; Q(2)  = 0.47). The metabolomic
      data analysis leads to a robust model also when the 3 groups of children were
      considered altogether (K = 0.80), indicating that each group is characterized by
      a specific metabolomic profile. Compounds related to retinoic acid, adenosine and
      vitamin D (Human Metabolome Database) were relevant for the discrimination
      between groups. CONCLUSION: The metabolomic profiling of EBC could clearly
      distinguish different biochemical-metabolic profiles in asthmatic children and
      enabled the severe asthma phenotype to be fully discriminated. The breathomics
      approach may therefore be suitable for discriminating between different asthma
      metabolic phenotypes.

PMID- 23157192
TI  - Activity-guided isolation of resveratrol oligomers from a grapevine-shoot extract
      using countercurrent chromatography.
AB  - An activity-guided isolation of bioactive stilbenes has been carried out with the
      grapevine-shoot extract Vineatrol 30. After hexane precipitation of the polymeric
      constituents, the stilbene mixture was separated on a preparative scale using low
      speed rotary countercurrent chromatography (LSRCCC). The antiproliferative
      activity of the separated LSRCCC fractions was then screened in the human cancer
      cell line A-431, and trans-resveratrol, trans-epsilon-viniferin, r-2-viniferin,
      hopeaphenol, and miyabenol C were identified as active principles. In addition, a
      new class of stilbene derivatives, which exhibit a gamma-lactam ring structure
      and exert a weak growth-inhibiting activity in A-431 cells, has been identified.

PMID- 23157193
TI  - Efficacy and safety of 'true' cinnamon (Cinnamomum zeylanicum) as a
      pharmaceutical agent in diabetes: a systematic review and meta-analysis.

PMID- 23157194
TI  - The metabolic rationale for a lack of cross-reactivity between sulfonamide
      antimicrobials and other sulfonamide-containing drugs.
AB  - Sulfonamide antimicrobials (sulfamethoxazole) contain an arylamine group,
      oxidized by CYP2C9 to the hydroxylamine with subsequent auto-oxidation to a
      highly reactive [-nitroso-] intermediate is a necessary (if not sufficient) cause
      of drug hypersensitivity. Accordingly, xenobiotics that do not contain an
      arylamine cannot generate this reactive intermediate and do not cross react with
      sulfonamide antimicrobials. Despite this well-attested observation, product
      labeling and direct-to-consumer advertising for non-arylamine therapeutic classes
      of drugs containing the sulfonamido- functional group persist with a warning of
      the potential for cross-reactivity. It is hoped that by offering an explicit
      rationale for the lack of cross-reactivity will provide medical practitioners
      with a level comfort to proceed with prescribing medications such as thiazide
      diuretics and celecoxib for patients with a history of hypersensitivity to
      sulfonamide antimicrobials.

PMID- 23157195
TI  - 2009-2010 seasonal influenza vaccination coverage among college students from 8
      universities in North Carolina.
AB  - OBJECTIVE: The authors sought to describe the 2009-2010 seasonal influenza
      vaccine coverage of college students. PARTICIPANTS: A total of 4,090 college
      students from 8 North Carolina universities participated in a confidential, Web
      based survey in October-November 2009. METHODS: Associations between self
      reported 2009-2010 seasonal influenza vaccination and demographic
      characteristics, campus activities, parental education, and e-mail usage were
      assessed by bivariate analyses and by a mixed-effects model adjusting for
      clustering by university. RESULTS: Overall, 20% of students (range 14%-30% by
      university) reported receiving 2009-2010 seasonal influenza vaccine. Being a
      freshman, attending a private university, having a college-educated parent, and
      participating in academic clubs/honor societies predicted receipt of influenza
      vaccine in the mixed-effects model. CONCLUSIONS: The self-reported 2009-2010
      influenza vaccine coverage was one-quarter of the 2020 Healthy People goal (80%)
      for healthy persons 18 to 64 years of age. College campuses have the opportunity
      to enhance influenza vaccine coverage among its diverse student populations.

PMID- 23157196
TI  - The relationships of information efficacy and media literacy skills to knowledge
      and self-efficacy for health-related decision making.
AB  - OBJECTIVE: To compare the extent to which information efficacy (confidence for
      acquiring useful information) and media literacy skills predict knowledge and
      self-efficacy for preventing or treating the health threat of influenza.
      PARTICIPANTS: A random-sample survey of 1,379 residential students enrolled at a
      northwestern public university was conducted in fall 2009. METHODS: Students
      accessed an Internet survey through a link provided in an e-mail. RESULTS:
      Students who self-diagnosed correctly demonstrated higher levels of media
      literacy skills than those who self-diagnosed incorrectly. Among those who self
      diagnosed incorrectly, the only predictor of knowledge was accessibility of
      information sources; low accessibility was associated with reduced knowledge.
      Information efficacy predicted self-efficacy for both groups. CONCLUSIONS: The
      results illustrate the limitations of information efficacy in the absence of
      media literacy skills. To decrease health risks, college health practitioners
      should promote media literacy while also ensuring easy access to high-quality
      information.

PMID- 23157197
TI  - The culture of high-risk alcohol use among club and intramural athletes.
AB  - OBJECTIVE: The purpose of this study was to examine the drinking patterns of club
      and intramural college athletes and compare their alcohol consumption, perceived
      norms around the excessive use of alcohol, experience of negative consequences,
      and employment of protective strategies with those of campus varsity athletes.
      PARTICIPANTS: A total of 442 undergraduate students attending a private, suburban
      institution in the Northeast participated in the American College Health
      Association National College Health Assessment-II Web survey in spring 2011.
      Thirty-five students identified themselves as varsity athletes, 76 identified as
      club sport athletes, and 196 students identified themselves as intramural
      athletes. METHODS: Survey responses were analyzed using Statistical Package for
      the Social Sciences. The Pearson's correlation coefficient and test for
      independence were applied to identify significant relationships between athlete
      status and identified variables related to alcohol use. RESULTS: Results
      indicated that there were significant correlations between athlete status and all
      variables, to varying degrees. CONCLUSIONS: These findings have implications for
      campus health promotion professionals and athletics program coordinators seeking
      to address high-risk alcohol use among college athletes.

PMID- 23157198
TI  - Implications of posttraumatic stress among military-affiliated and civilian
      students.
AB  - OBJECTIVES: To determine whether posttraumatic stress (PTS) symptoms are
      associated with problem drinking and alcohol-related consequences, as well as
      academic correlates among military-affiliated and civilian students.
      PARTICIPANTS: The final sample (n = 248) included 78 combat-exposed student
      service members/veterans, 53 non-combat-exposed student service members/
      veterans, 38 ROTC (Reserve Officers' Training Corps) students, and 79 civilian
      students. METHODS: Self-report data were collected spring 2011 via a Web-based
      survey measuring PTS, problem drinking, alcohol-related consequences, grade point
      average, educational self-efficacy, academic amotivation, and persistence.
      RESULTS: Military students exposed to combat-related trauma reported
      significantly greater PTS symptoms than other military and civilian groups. PTS
      symptoms were associated with problem drinking and alcohol-related consequences
      for all groups, yet unrelated to academic correlates among those exposed to
      combat-related trauma. CONCLUSION: This study adds to the scant literature base
      exploring the unique characteristics of student service members/veterans in
      higher education.

PMID- 23157199
TI  - Relative efficacy of a pregnancy, sexually transmitted infection, or human
      immunodeficiency virus prevention-focused intervention on changing sexual risk
      behavior among young adults.
AB  - OBJECTIVES: Despite findings suggesting that young adults are more concerned
      about experiencing an unplanned pregnancy or contracting a sexually transmitted
      infection (STI) than becoming human immunodeficiency virus (HIV) infected, no
      empirical work has investigated whether the specific focus of an intervention may
      be more or less efficacious at changing sexual behavior. PARTICIPANTS:
      Participants were 198 college students randomized to 1 of 4 conditions: pregnancy
      intervention, STI intervention, HIV intervention, or a control condition during
      2008-2009. METHODS: The authors compared the efficacy of 3 theory-based, sexual
      risk-reduction interventions that were exactly the same except for an exclusive
      focus on preventing pregnancy, STI, or HIV. Condom use and risky sexual behavior
      were assessed at baseline and 4-week and 8-week follow-up. RESULTS: Participants
      exposed to the pregnancy or STI interventions reported greater condom use and
      less risky sexual behavior than those exposed to the HIV intervention.
      CONCLUSIONS: The focus of sexual risk-reduction interventions may lead to
      differential behavior change among young adults.

PMID- 23157200
TI  - An evaluation of behavioral health compliance and microbial risk factors on
      student populations within a high-density campus.
AB  - OBJECTIVE: The aim of this Canadian study was to assess student behavioral
      response to disease transmission risk, while identifying high microbial
      deposition/transmission sites. PARTICIPANTS: A student survey was conducted
      during October 2009. METHODS: The methods included a survey of students to assess
      use of health services, vaccination compliance, and hygiene along with a
      microbial analysis of potential transmission sites targeting specific residence
      buildings on campus. RESULTS: Results indicated that most students maintained
      that they were worried about H1N1 and reported making changes in hygienic
      behavior, with the majority not planning to be vaccinated. The microbial analysis
      indicated contamination of fomites in co-ed residences to be higher than either
      male or female student residences. CONCLUSIONS: A consideration of physical space
      along with behavioral factors is required in order to properly assess risk
      pathways in the establishment of an evidence-based infection control plan for
      universities and their contiguous communities.

PMID- 23157201
TI  - Students left behind: the limitations of university-based health insurance for
      students with mental illnesses.
AB  - A growing trend in college and university health care is the requirement that
      students demonstrate proof of health insurance prior to enrollment. An increasing
      number of schools are contracting with insurance companies to provide students
      with school-based options for health insurance. Although this is advantageous to
      students in some ways, tying health insurance coverage to school enrollment can
      leave students vulnerable when they are most in need of help. Students whose
      health insurance is contingent upon their enrollment face significant lapses in
      coverage when they are required to leave school. This is especially challenging
      for students with mental illnesses whose treatment needs often go unmet in the
      absence of that coverage. The limitations in this system must be addressed as an
      increasing number of universities and students opt for university-based health
      insurance plans.

PMID- 23157203
TI  - Diagnosis and treatment of factor VIII and IX inhibitors in congenital
      haemophilia: (4th edition). UK Haemophilia Centre Doctors Organization.

PMID- 23157205
TI  - Hypothalamic brain-derived neurotrophic factor regulates glucagon secretion
      mediated by pancreatic efferent nerves.
AB  - Understanding the molecular mechanism of the regulation of glucagon secretion is
      critical for treating the dysfunction of alpha cells observed in diabetes.
      Glucagon-like peptide (GLP)-1 analogues reduce plasma glucagon and are assumed to
      contribute to their action to lower blood glucose. It has previously been
      demonstrated that the central administration of brain-derived neurotrophic factor
      (BDNF) improves glucose metabolism by a mechanism independent of feeding
      behaviour in obese subjects. Using male rats, we examined whether BDNF influences
      glucagon secretion from alpha cells via the the central nervous system. We
      investigate whether: (i) the central infusion of BDNF stimulates glucagon and/or
      insulin secretion via the pancreatic efferent nerve from the hypothalamus; (ii)
      the intraportal infusion of GLP-1 regulates glucose metabolism via the central
      and peripheral nervous system; and (iii) BDNF receptor and/or BDNF-positive
      fibres are localised near alpha cells of islets. The portal glucagon level
      decreased with the central administration of BDNF (n = 6, in each; P < 0.05); in
      contrast, there was no significant change in portal insulin, peripheral glucagon
      and insulin levels with the same treatment. This reduction of glucagon secretion
      was abolished by pancreatic efferent denervation (n = 6, in each; P < 0.05). In
      an immunohistochemical study, pancreatic alpha cells were stained specifically
      with BDNF and tyrosine-related kinase B, a specific receptor for BDNF, and alpha
      cells were also co-localised with BDNF. Moreover, intraportal administration of
      GLP-1 decreased glucagon secretion, as well as blood glucose, whereas it
      increased the BDNF content in the pancreas; these effects were inhibited with the
      central infusion of BDNF antibody (n = 6, in each; P < 0.05). BDNF and GLP-1
      affect glucose metabolism and modulate glucagon secretion from pancreatic alpha
      cells via the central and peripheral nervous systems.

PMID- 23157204
TI  - Parallel and competitive pathways for substrate desaturation, hydroxylation, and
      radical rearrangement by the non-heme diiron hydroxylase AlkB.
AB  - A purified and highly active form of the non-heme diiron hydroxylase AlkB was
      investigated using the diagnostic probe substrate norcarane. The reaction
      afforded C2 (26%) and C3 (43%) hydroxylation and desaturation products (31%).
      Initial C-H cleavage at C2 led to 7% C2 hydroxylation and 19% 3
      hydroxymethylcyclohexene, a rearrangement product characteristic of a radical
      rearrangement pathway. A deuterated substrate analogue, 3,3,4,4-norcarane-d(4),
      afforded drastically reduced amounts of C3 alcohol (8%) and desaturation products
      (5%), while the radical rearranged alcohol was now the major product (65%). This
      change in product ratios indicates a large kinetic hydrogen isotope effect of ~20
      for both the C-H hydroxylation at C3 and the desaturation pathway, with all of
      the desaturation originating via hydrogen abstraction at C3 and not C2. The data
      indicate that AlkB reacts with norcarane via initial C-H hydrogen abstraction
      from C2 or C3 and that the three pathways, C3 hydroxylation, C3 desaturation, and
      C2 hydroxylation/radical rearrangement, are parallel and competitive. Thus, the
      incipient radical at C3 either reacts with the iron-oxo center to form an alcohol
      or proceeds along the desaturation pathway via a second H-abstraction to afford
      both 2-norcarene and 3-norcarene. Subsequent reactions of these norcarenes lead
      to detectable amounts of hydroxylation products and toluene. By contrast, the 2
      norcaranyl radical intermediate leads to C2 hydroxylation and the diagnostic
      radical rearrangement, but this radical apparently does not afford desaturation
      products. The results indicate that C-H hydroxylation and desaturation follow
      analogous stepwise reaction channels via carbon radicals that diverge at the
      product-forming step.

PMID- 23157206
TI  - Identification of differentially expressed genes and pathways between primary
      osteoarthritis and endemic osteoarthritis (Kashin-Beck disease).
AB  - OBJECTIVES: Primary osteoarthritis (OA) and Kashin-Beck disease (KBD) exhibit
      similar clinical manifestations and common articular cartilage lesions. Revealing
      the pathogenetic differences between OA and KBD is helpful for differential
      diagnosis and may provide new insights into the pathogenesis of OA and KBD. In
      this study, we compared the genome-wide gene ontology (GO) and pathway expression
      patterns of articular cartilage derived from both OA and KBD patients. METHODS:
      Total RNA was isolated, amplified, labelled, and hybridized using Agilent whole
      genome microarray analysis. Gene set enrichment analysis (GSEA) was used to
      identify differentially expressed genes and pathways between OA and KBD. Nine
      differentially expressed GO categories and 85 differentially expressed pathways
      were identified by this study. RESULTS: The reactive oxygen species (ROS)-related
      HOUSTIS_ROS pathway and the vascular endothelial growth factor (VEGF)-related
      ABE_VEGFA_TARGETS_2HR pathway were significantly up-regulated in OA compared to
      KBD. Higher expression levels of the collagen-related COLLAGEN GO,
      EXTRACELLULAR_MATRIX_PART GO, and nitric oxide (NO)-related BIOCARTA_NO1_PATHWAY
      pathways were detected in KBD than in OA. CONCLUSIONS: ROS-induced cartilage
      lesions seem to be more involved in the pathogenesis of OA whereas NO-mediated
      chondrocyte apoptosis contributes more to the development of KBD.

PMID- 23157208
TI  - Productive Ward initiative promotes better communication between mental health
      teams and ensures timely discharge for patients.
AB  - The Productive Ward is an initiative whereby nursing staff are empowered to bring
      about changes in the workplace to streamline systems and release time to care for
      patients. It is an evidence-based approach, which brings about improved clinical
      and safety outcomes. This paper discusses how three of the Productive Ward
      Modules - Ward Round, Admissions and Planned Discharge, and Patient Status At a
      Glance - have meshed to promote better communication and working between
      inpatient nursing and medical teams, Home Treatment Team and Community Mental
      Health Team, and to endeavour to ensure timely discharge for patients.

PMID- 23157207
TI  - Kidney, pancreas and liver allocation and distribution in the United States.
AB  - Kidney transplant and liver transplant are the treatments of choice for patients
      with end-stage renal disease and end-stage liver disease, respectively. Pancreas
      transplant is most commonly performed along with kidney transplant in diabetic
      end-stage renal disease patients. Despite a steady increase in the numbers of
      kidney and liver transplants performed each year in the United States, a
      significant shortage of kidneys and livers available for transplant remains.
      Organ allocation is the process the Organ Procurement and Transplantation Network
      (OPTN) uses to determine which candidates are offered which deceased donor
      organs. OPTN is charged with ensuring the effectiveness, efficiency and equity of
      organ sharing in the national system of organ allocation. The policy has changed
      incrementally over time in efforts to optimize allocation to meet these often
      competing goals. This review describes the history, current status and future
      direction of policies regarding the allocation of abdominal organs for
      transplant, namely the kidney, liver and pancreas, in the United States.

PMID- 23157209
TI  - Effects of masticatory muscle training on maximum bite force and muscular
      endurance.
AB  - OBJECTIVE: This study evaluates the effects of chewing training on strength and
      endurance of the masticatory muscles. MATERIALS AND METHODS: Of the 49 healthy
      young adults included in the study, nine served as controls for a baseline
      measurement of bite force. The 40 participants who actively trained their
      masticatory muscles were randomly divided into a 'continuous training group'
      (CTG) and an 'intermittent training group' (ITG). The participants performed oral
      motor training by clenching silicon tubes (Chewy Tubes(TM)) according to a
      designed protocol. The muscular strength was studied in terms of maximum bite
      force. Muscular endurance was evaluated by measuring the duration for which the
      participants held 50% of their maximum bite force value. RESULTS: Both the
      maximum bite force and the muscular endurance capacity increased after intensive
      training for both groups. After 2 months, the ITG stopped training for 1 month.
      At this point, a significant difference was identified both in the mean bite
      force values and the mean muscular endurance duration: the ITG exhibited lower
      values. For both groups, the highest values were attained after 3 months of
      training. The maximum bite force values and the muscular endurance duration were
      observed to follow similar patterns. The effects attained decreased rapidly in
      both groups when the training stopped. CONCLUSIONS: For both the continuous and
      intermittent training groups, 4 months of chewing exercises strengthened
      masticatory muscles, but such effects diminished gradually for both groups when
      the exercises stopped.

PMID- 23157210
TI  - Nickel(II) complexes containing a pyrrole-diphosphine pincer ligand.
AB  - A new pincer ligand, (P(2)(Ph)Pyr)(-), based on the anion of 2,5
      bis[(diphenylphosphino)methyl]pyrrole has been prepared in four steps from
      pyrrole. The ligand undergoes oxidation to diphosphine oxide under ambient
      conditions and was therefore isolated as its borane adduct, H(P(2)(Ph)Pyr).2BH(3)
      (2). Delivery of the ligand to nickel(II) was accomplished by the direct reaction
      of NiCl(2) with 2 in the presence of Et(2)NH to afford [NiCl(P(2)(Ph)Pyr)]. Salt
      metathesis reactions of the chloro complex afford new compounds including
      [Ni(CH(3))(P(2)(Ph)Pyr)] and [Ni(NCCH(3))(P(2)(Ph)Pyr)](OTf). In all cases, the
      ligand gives rise to diamagnetic square-planar complexes, which have been fully
      characterized in solution and the solid state. All complexes examined display an
      irreversible oxidation to nickel(III) according to cyclic voltammetry. Reduction
      of the chloro complex in dichloromethane results in an electrocatalytic process,
      whereas reduction in tetrahydrofuran leads to the irreversible formation of a
      nickel(I) species.

PMID- 23157211
TI  - The use of self-retaining barbed suture for inner layer renorrhaphy significantly
      reduces warm ischemia time in laparoscopic partial nephrectomy: outcomes of a
      matched-pair analysis.
AB  - PURPOSE: To investigate the efficacy of self-retaining barbed suture (SRBS) on
      reducing renorrhaphy time and warm ischemia time (WIT) during laparoscopic
      partial nephrectomy (LPN), in comparison with conventional polyglactin suture.
      PATIENTS AND METHODS: Between February 2008 and June 2012, 115 patients underwent
      LPN for renal tumors at our institution. Among them, the patients whose inner
      layer renorrhaphy was performed using SRBS (group 1, n=33) or polyglactin suture
      (group 2, n=33) were retrospectively identified from prospectively collected
      institutional laparoscopic database (unmatched comparison). Furthermore, 17
      patients from each group were matched at a 1:1 ratio in terms of sex, age, body
      mass index, preoperative aspects and dimensions used for an anatomic (PADUA)
      classification scoring system, and operative approach
      (transperitoneoscopic/retroperitoneoscopic) to eliminate the effects of these
      variables on WIT (matched-pair comparison). Demographic, perioperative, and
      pathologic parameters were evaluated between groups in both unmatched and matched
      pair comparison. RESULTS: The perioperative parameters including inner layer
      renorrhaphy time, WIT, estimated blood loss, operative time, length of hospital
      stay, and complication rate were not statistically different between the two
      groups in the unmatched comparison. Median PADUA score (9 vs 8, P=0.006), median
      preoperative (4 cm vs 3.6 cm, P=0.049), and pathologic (4.5 cm vs 3.5 cm,
      P=0.009) tumor size, however, were significantly higher in group 1. In the
      matched-pair analysis, inner layer renorrhaphy time (350 sec vs 505 sec, P=0.004)
      and WIT (19 min vs 28 min, P=0.037) were significantly reduced with the use of
      SRBS in group 1 without a difference of median PADUA score (8 vs 8, P=1), median
      preoperative (3.8 cm vs 4 cm, P=0.959), and pathologic (4.2 cm vs 4 cm, P=0.284)
      tumor size. CONCLUSIONS: The SRBS significantly reduced inner layer renorrhaphy
      time and WIT during LPN and may enable urologists to perform LPN in more
      challenging and larger tumors, in comparison with conventional polyglactin
      suture.

PMID- 23157212
TI  - Directing cardiomyogenic differentiation of human pluripotent stem cells by
      plasmid-based transient overexpression of cardiac transcription factors.
AB  - Cardiomyocytes (CMs) derived from human pluripotent stem cells (hPSCs) possess a
      high potential for regenerative medicine. Previous publications suggested that
      viral transduction of a defined set of transcription factors (TFs) known to play
      pivotal roles in heart development also increases cardiomyogenesis in vitro upon
      overexpression in mouse or human ES cells. To circumvent issues associated with
      viral approaches such as insertional mutagenesis, we have established a transient
      transfection system for straightforward testing of TF combinations. Applying this
      method, the transfection efficiency and the temporal pattern of transgene
      expression were extensively assessed in hPSCs by quantitative real time
      polymerase chain reaction (qRT-PCR), TF-specific immunofluorescence analysis, and
      flow cytometry. Testing TF combinations in our approach revealed that BAF60C,
      GATA4, and MESP1 (BGM) were most effective for cardiac forward programming in
      human induced pluripotent stem cell lines and human ES cells as well. Removal of
      BAF60C slightly diminished formation of CM-like cells, whereas depletion of GATA4
      or MESP1 abolished cardiomyogenesis. Each of these TFs alone had no inductive
      effect. In addition, we have noted sensitivity of CM formation to cell density
      effects, which highlights the necessity for cautious analysis when interpreting
      TF-directed lineage induction. In summary, this is the first report on TF-induced
      cardiomyogenesis of hPSCs applying a transient, nonintegrating method of cell
      transfection.

PMID- 23157213
TI  - Erdosteine protects rat testis tissue from hypoxic injury by reducing apoptotic
      cell death.
AB  - The purpose of this study was to examine the effects of hypobaric hypoxia on
      testis morphology and the effects of erdosteine on testis tissue. Caspase-3 and
      hypoxia-inducible factor 1alpha expressions were detected by
      immunohistochemistry. Adult male Wistar rats were placed in a hypobaric hypoxic
      chamber. Rats in the erdosteine group were exposed to the same conditions and
      treated orally with erdosteine (20 mg kg(-1) daily) at the same time from the
      first day of hypoxic exposure for 2 weeks. The normoxia group was evaluated as
      the control. The hypoxia group showed decreased height of spermatogenic
      epithelium in some seminiferous tubules, vacuolisation in spermatogenic
      epithelial cells, deterioration and gaps in the basal membrane and an increase in
      blood vessels in the interstitial area. The erdosteine group showed amelioration
      of both epithelial cell vacuolisation and basal membrane deterioration. Numbers
      of hypoxia-inducible factor 1alpha-immunostained Sertoli and Leydig cells were
      significantly higher in the hypoxia group than in the erdosteine group. The
      number of seminiferous tubules with caspase-3-immunostained germ cells was
      highest in the hypoxia group and decreased in the erdosteine and normoxia groups
      respectively. Based on these observations, erdosteine protects testis tissue from
      hypoxic injury by reducing apoptotic cell death.

PMID- 23157215
TI  - Features of airway remodeling in different types of Chinese chronic
      rhinosinusitis are associated with inflammation patterns.
AB  - BACKGROUND: The remodeling patterns in different types of chronic rhinosinusitis
      (CRS) have rarely been compared, particularly the difference between eosinophilic
      and noneosinophilic CRS with nasal polyps (CRSwNP). Moreover, whether there is a
      link between remodeling and inflammation remains controversial. OBJECTIVE: To
      directly compare the remodeling features of different CRS and to explore their
      relationship with inflammation in Chinese patients. METHODS: Histologic
      characteristics of surgical samples were analyzed in 33 controls, 72 eosinophilic
      and 76 noneosinophilic CRSwNP, and 72 CRS without nasal polyps (CRSsNP) patients.
      Tissue samples from 38 controls, 26 eosinophilic and 26 noneosinophilic CRSwNP,
      and 32 CRSsNP patients were measured for mRNA and/or protein expression of
      profibrotic growth factors, metalloproteinases (MMPs), tissue inhibitor of
      metalloproteinases (TIMPs), hypoxia-inducible factor (HIF)-1alpha, interleukin
      (IL)-8, eosinophil cationic protein (ECP), and myeloperoxidase (MPO). RESULTS:
      The amount of collagen decreased, whereas the edema scores increased, from CRSsNP
      to noneosinophilic CRSwNP and to eosinophilic CRSwNP. Transforming growth factor
      (TGF)-beta2 protein levels were enhanced in CRSsNP compared with CRSwNP. TIMP-4
      protein levels decreased in eosinophilic CRSwNP compared with noneosinophilic
      CRSwNP and CRSsNP. The number of neutrophils decreased from CRSsNP to
      noneosinophilic CRSwNP and to eosinophilic CRSwNP. ECP levels were only up
      regulated in eosinophilic CRSwNP. ECP levels and neutrophil number correlated
      positively with the severity of edema and fibrosis, respectively. Neutrophils
      were the major sources of TGF-beta2 in CRSsNP and noneosinophilic CRSwNP.
      CONCLUSION: Distinct remodeling patterns are revealed for different types of CRS,
      particularly for eosinophilic and noneosinophilic CRSwNP. Tissue remodeling
      associates with inflammation in CRS.

PMID- 23157214
TI  - A standard numbering scheme for thiamine diphosphate-dependent decarboxylases.
AB  - BACKGROUND: Standard numbering schemes for families of homologous proteins allow
      for the unambiguous identification of functionally and structurally relevant
      residues, to communicate results on mutations, and to systematically analyse
      sequence-function relationships in protein families. Standard numbering schemes
      have been successfully implemented for several protein families, including
      lactamases and antibodies, whereas a numbering scheme for the structural family
      of thiamine-diphosphate (ThDP) -dependent decarboxylases, a large subfamily of
      the class of ThDP-dependent enzymes encompassing pyruvate-, benzoylformate-, 2
      oxo acid-, indolpyruvate- and phenylpyruvate decarboxylases, benzaldehyde lyase,
      acetohydroxyacid synthases and 2-succinyl-5-enolpyruvyl-6-hydroxy-3
      cyclohexadiene-1-carboxylate synthase (MenD) is still missing.Despite a high
      structural similarity between the members of the ThDP-dependent decarboxylases,
      their sequences are diverse and make a pairwise sequence comparison of protein
      family members difficult. RESULTS: We developed and validated a standard
      numbering scheme for the family of ThDP-dependent decarboxylases. A profile
      hidden Markov model (HMM) was created using a set of representative sequences
      from the family of ThDP-dependent decarboxylases. The pyruvate decarboxylase from
      S. cerevisiae (PDB: 2VK8) was chosen as a reference because it is a well
      characterized enzyme. The crystal structure with the PDB identifier 2VK8
      encompasses the structure of the ScPDC mutant E477Q, the cofactors ThDP and
      Mg(2+) as well as the substrate analogue (2S)-2-hydroxypropanoic acid. The
      absolute numbering of this reference sequence was transferred to all members of
      the ThDP-dependent decarboxylase protein family. Subsequently, the numbering
      scheme was integrated into the already established Thiamine-diphosphate dependent
      Enzyme Engineering Database (TEED) and was used to systematically analyze
      functionally and structurally relevant positions in the superfamily of ThDP
      dependent decarboxylases. CONCLUSIONS: The numbering scheme serves as a tool for
      the reliable sequence alignment of ThDP-dependent decarboxylases and the
      unambiguous identification and communication of corresponding positions. Thus, it
      is the basis for the systematic and automated analysis of sequence-encoded
      properties such as structural and functional relevance of amino acid positions,
      because the analysis of conserved positions, the identification of correlated
      mutations and the determination of subfamily specific amino acid distributions
      depend on reliable multisequence alignments and the unambiguous identification of
      the alignment columns. The method is reliable and robust and can easily be
      adapted to further protein families.

PMID- 23157216
TI  - Polypharmacy and food-drug interactions among older persons: a review.
AB  - Polypharmacy is generally defined as the use of 5 or more prescription
      medications on a regular basis. The average number of prescribed and over-the
      counter medications used by community-dwelling older adults per day in the United
      States is 6 medications, and the number used by institutionalized older persons
      is 9 medications. Almost all medications affect nutriture, either directly or
      indirectly, and nutriture affects drug disposition and effect. This review will
      highlight the issues surrounding polypharmacy, food-drug interactions, and the
      consequences of these interactions for the older adult.

PMID- 23157217
TI  - A state-level examination of the association between home and community-based
      services and rates of nursing home residency with special attention to nutrition
      programs.
AB  - Federal food and nutrition programs implemented by the Administration on Aging
      and funded by the Older Americans Act (OAA) seek to enable older adults to remain
      in their homes and communities through a comprehensive, coordinated, and cost
      effective array of services. We hypothesized that expenditures devoted to
      nutrition programs for home and community-based nutrition services were inversely
      related to changes in state-level rates of institutionalization for older adults
      from one year to the next, such that states that spend more money per capita on
      community-based nutrition programs would have smaller increases or greater
      decreases in rates of institutionalization, controlling for expenditures on other
      home and community-based services. We found, however, that there was not an
      effect of OAA Nutrition Services on the change in rates of nursing home
      residency. We noted, though, that states that direct a greater proportion of
      their long-term care expenditures to home and community-based services appear to
      have more reduction in their rates of nursing home residency. Further
      longitudinal work at the state and individual levels is warranted.

PMID- 23157219
TI  - Reversible off-on fluorescence probe for hypoxia and imaging of hypoxia-normoxia
      cycles in live cells.
AB  - We report a fully reversible off-on fluorescence probe for hypoxia. The design
      employs QSY-21 as a Forster resonance energy transfer (FRET) acceptor and cyanine
      dye Cy5 as a FRET donor, based on our finding that QSY-21 undergoes one-electron
      bioreduction to the radical under hypoxia, with an absorbance decrease at 660 nm.
      At that point, FRET can no longer occur, and the dye becomes strongly
      fluorescent. Upon recovery of normoxia, the radical is immediately reoxidized to
      QSY-21, with loss of fluorescence due to restoration of FRET. We show that this
      probe, RHyCy5, can monitor repeated hypoxia-normoxia cycles in live cells.

PMID- 23157220
TI  - Family history of Type 1 diabetes affects insulin secretion in patients with
      'Type 2' diabetes.
AB  - AIMS: The aim was to evaluate the impact of family history of diabetes on the
      phenotype of patients diagnosed with Type 2 diabetes and the frequency of
      susceptibility genotypes. METHODS: Patients with Type 2 diabetes with family
      history for both Type 1 and Type 2 diabetes (FH(MIX, n) = 196) or Type 2 diabetes
      only (FH(T2), n = 139) matched for age, sex, BMI and age at diagnosis, underwent
      an oral glucose tolerance test and a combined glucagon test and insulin tolerance
      test. Glutamic acid decarboxylase (GAD) antibodies and major Type 1 and Type 2
      diabetes susceptibility gene variants were analysed. Patients were stratified
      into groups according to family history or GAD antibody positivity (GADA+, GADA-)
      or a combination of these (GADA+/FH(MIX), GADA+/FH(T2), GADA-/FH(MIX), GADA
      /FH(T2)). RESULTS: Compared with other patients, those with FH(MIX) more often
      had GAD antibodies (14.3 vs. 4.3%, P = 0.003), and those with both FH(MIX) and
      GAD antibodies had the highest frequency of insulin deficiency (stimulated serum
      C-peptide < 0.7 nmol/l, GADA+/FH(MIX) 46.4% vs. GADA-/FH(MIX) 9.5% (P < 0.00001),
      GADA-/FH(T2) 4.5% (P < 0.00001), GADA+/FH(T2) 0%). Patients with GADA+/FH(MIX)
      more often had HLA-DQB1 risk genotypes compared with patients with GADA-/FH(MIX)
      or GADA-/FH(T2D) (47 vs. 23 or 14%, P = 0.05 and P < 0.00001, respectively). In
      logistic regression analyses, FH(MIX), GAD antibody positivity and HLA risk
      genotypes were independently associated with insulin deficiency. CONCLUSION: A
      family history for both type 1 and type 2 diabetes was associated with higher
      prevalence of GAD antibodies and HLA-DQB1 risk genotypes than a family history of
      type 2 diabetes only, and was associated with earlier and more severe development
      of insulin deficiency, which was only partially explained by GAD antibodies and
      HLA.

PMID- 23157222
TI  - Nonfouling capture-release substrates based on polymer brushes for separation of
      water-dispersed oil droplets.
AB  - We have demonstrated capture and release of underwater-oil droplets based on
      fouling-resistant surfaces coated with pH-responsive polymer brushes. In response
      to the change of environmental pH, oil droplets were captured on the polymer
      brush-modified surfaces in the high adhesion state. As the droplet volume
      increased upon coalescence with other oil droplets in the aqueous phase, the
      captured droplets eventually self-released from the surfaces under the influence
      of buoyancy and rose to the air-water interface. The fact that the polymer brush
      surfaces were partially oil-wettable (high oil-in-water contact angles) enabled
      the adhesion but not the spreading of oil droplets. This allowed buoyancy release
      of oil droplets and led to fouling-resistant surfaces that could be reused for
      capture-release of more oil droplets. The practicality and versatility of this
      oil droplet capture-release system was demonstrated using monodisperse and
      polydisperse hydrocarbon oil compositions in purified water, tap water, and
      brines in which the salt concentration was as high as that of seawater.

PMID- 23157221
TI  - Proteomic approaches to analyze protein tyrosine nitration.
AB  - SIGNIFICANCE: The conversion of protein-bound Tyr residues to 3-nitrotyrosine
      (3NY) can occur during nitrative stress and has been correlated to aging and many
      disease states. Proteomic analysis of this post-translational modification, using
      mass spectrometry-based techniques, is crucial for understanding its potential
      role in pathological and physiological processes. RECENT ADVANCES: To overcome
      some of the disadvantages inherent to well-established nitroproteomic methods
      using anti-3NY antibodies and gel-based separations, methods involving
      multidimensional chromatography, precursor ion scanning, and/or chemical
      derivatization have emerged for both identification and quantitation of protein
      nitration sites. A few of these methods have successfully detected endogenous 3NY
      modifications from biological samples. CRITICAL ISSUES: While model systems often
      show promising results, identification of endogenous 3NY modifications remains
      largely elusive. The frequently low abundance of nitrated proteins in vivo, even
      under inflammatory conditions, is especially challenging, and sample loss due to
      derivatization and cleaning may become significant. FUTURE DIRECTIONS: Continued
      efforts to avoid interference from non-nitrated peptides without sacrificing
      recovery of nitrated peptides are needed. Quantitative methods are emerging and
      are crucial for identifying endogenous modifications that may have significant
      biological impacts.

PMID- 23157223
TI  - Identification of phenolic constituents in Cichorium endivia var. crispum and
      var. latifolium salads by high-performance liquid chromatography with diode array
      detection and electrospray ioniziation tandem mass spectrometry.
AB  - Chicory is a widely consumed vegetable and a source of phenolic compounds.
      Phenolic acid and flavonoid derivatives were identified in Cichorium endivia var.
      crispum and var. latifolium and fully characterized using complementary
      information from two different high-performance liquid chromatography detectors,
      diode array and mass spectrometer, in positive and negative modes. We describe
      about 40 phenolic compounds, some of which have never previously been reported in
      these plants, such as hydroxycinnamic acid derivatives (i.e., different mono- and
      dicaffeoylquinic acid isomers) and mono- and diglycosides of quercetin,
      kaempferol, and myricetin (differing also by the glycosylation site). These data
      provide a contribution to a more exhaustive identification of phenolic compounds
      in C. endivia vegetables.

PMID- 23157225
TI  - Distribution of regulatory T cells and interaction with dendritic cells in the
      synovium of rheumatoid arthritis.
AB  - OBJECTIVES: The aim of this study was to investigate the tissue distribution of
      regulatory T cells (Treg cells) and their interaction with dendritic cells (DCs)
      in synovium from patients with rheumatoid arthritis (RA) or osteoarthritis (OA).
      METHODS: Immunohistochemical staining was used to investigate the distribution of
      Treg cells and the interaction between Treg cells and DCs in RA (n = 30) and OA
      synovium (n = 8). mRNA levels were measured by quantitative real-time reverse
      transcription polymerase chain reaction (RT-PCR). RESULTS: Large numbers of Treg
      cells were observed in lymphoid aggregates and perivenular infiltration areas in
      the RA synovium. Specific cellular markers for Treg cells (Foxp3, CD39, LAG-3,
      and Nrp-1) were found in lymphoid aggregates, perivenular infiltration, and
      scattered in lining layer areas. As molecular markers for DCs, DC-LAMP, DEC-205,
      CD80/86, and CD83 were also detected in the lymphoid aggregates and perivenular
      infiltration areas in RA. Furthermore, the co-localization of Treg cells and DCs
      was confined mainly in the lymphoid aggregation areas. The number of DCs
      increased significantly more than the number of Treg cells with inflammatory
      progression in RA. mRNA expression of the cellular markers for Treg cells (Foxp3,
      LAG-3, and Nrp-1) and the molecular markers for DCs (DC-LAMP and DEC-205) was
      increased in RA compared with OA synovium. CONCLUSIONS: Our results indicate that
      DCs play a dominant role in regulating the activation and progression of immune
      responses in RA, even though the number of Treg cells was upregulated at the same
      time. This suggests that Treg cells do not function normally to suppress the
      maturation of DCs in the RA synovium.

PMID- 23157226
TI  - 4-Aminocyclopentane-1,3-diols as platforms for diversity: synthesis of anandamide
      analogs.
AB  - Starting from cyclopentadiene, two racemic mixtures of 4-aminocyclopentane-1,3
      diols were prepared in 8 steps and characterized. Structure determination proved
      the anticipated trans-orientation of the two oxygen atoms with respect to the
      plane of the ring. The fragment-like new compounds are small and hydrophilic,
      devoid of rotatable bonds, and offer stereochemically defined attachment points
      for substituents. Thus, these platforms for diversity are suitable starting
      points for the construction of combinatorial libraries of lead-like 4
      amidocyclopentane-1,3-diols or natural product analogs. As a proof of concept,
      cyclopentanoid anandamide analogs were prepared using these molecular platforms
      and evaluated as tools for the investigation of unresolved issues in the
      molecular biology of anandamide. 

PMID- 23157227
TI  - Aggregation behavior of amphiphilic p(HPMA)-co-p(LMA) copolymers studied by FCS
      and EPR spectroscopy.
AB  - A combined study of fluorescence correlation spectroscopy and electron
      paramagnetic resonance spectroscopy gave a unique picture of p(HPMA)-co-p(LMA)
      copolymers in aqueous solutions, ranging from the size of micelles and aggregates
      to the composition of the interior of these self-assembled systems. P(HPMA)-co
      p(LMA) copolymers have shown high potential as brain drug delivery systems, and a
      detailed study of their physicochemical properties can help to elucidate their
      mechanism of action. Applying two complementary techniques, we found that the
      self-assembly behavior as well as the strength of hydrophobic attraction of the
      amphiphilic copolymers can be tuned by the hydrophobic LMA content or the
      presence of hydrophobic molecules or domains. Studies on the dependence of the
      hydrophobic lauryl side chain content on the aggregation behavior revealed that
      above 5 mol % laury side-chain copolymers self-assemble into intrachain micelles
      and larger aggregates. Above this critical alkyl chain content, p(HPMA)-co-p(LMA)
      copolymers can solubilize the model drug domperidone and exhibit the tendency to
      interact with model cell membranes.

PMID- 23157224
TI  - JAK2-V617F-mediated signalling is dependent on lipid rafts and statins inhibit
      JAK2-V617F-dependent cell growth.
AB  - Aberrant JAK2 signalling plays an important role in the aetiology of
      myeloproliferative neoplasms (MPNs). JAK2 inhibitors, however, do not readily
      eliminate neoplastic MPN cells and thus do not induce patient remission. Further
      understanding JAK2 signalling in MPNs may uncover novel avenues for therapeutic
      intervention. Recent work has suggested a potential role for cellular cholesterol
      in the activation of JAK2 by the erythropoietin receptor and in the development
      of an MPN-like disorder in mice. Our study demonstrates for the first time that
      the MPN-associated JAK2-V617F kinase localizes to lipid rafts and that JAK2-V617F
      dependent signalling is inhibited by lipid raft disrupting agents, which target
      membrane cholesterol, a critical component of rafts. We also show for the first
      time that statins, 3-hydroxy-3-methyl-glutaryl coenzyme A (HMG-CoA) reductase
      inhibitors, widely used to treat hypercholesterolaemia, induce apoptosis and
      inhibit JAK2-V617F-dependent cell growth. These cells are more sensitive to
      statin treatment than non-JAK2-V617F-dependent cells. Importantly, statin
      treatment inhibited erythropoietin-independent erythroid colony formation of
      primary cells from MPN patients, but had no effect on erythroid colony formation
      from healthy individuals. Our study is the first to demonstrate that JAK2-V617F
      signalling is dependent on lipid rafts and that statins may be effective in a
      potential therapeutic approach for MPNs.

PMID- 23157229
TI  - Differential expression of Toll-like receptor pathway genes in chronic
      rhinosinusitis with or without nasal polyps.
AB  - CONCLUSIONS: Our results indicate that chronic rhinosinusitis without nasal
      polyps (CRSsNP) is characterized by the down-regulation of a Toll-like receptor
      (TLR)-mediated signaling pathway and such a deficiency within the innate immune
      system may contribute to the inflammatory process of CRSsNP. In contrast, the
      inflammatory process found in CRS with nasal polyps (CRSwNP) is characterized by
      an excessively activated TLR-mediated signaling pathway, which may contribute to
      the formation of nasal polyps. This study suggests that the pathophysiologic
      mechanism of CRSsNP and CRSwNP is different. OBJECTIVE: The nasal mucosa
      expresses a variety of TLRs that serve in recognizing microorganisms. We
      investigated the gene expression of a TLR-mediated signaling pathway within two
      distinctive patient subgroups: CRSwNP and CRSsNP. METHODS: Nasal mucosal tissue
      was obtained from 78 subjects with CRS and 23 control subjects. qRT-PCR and
      immunohistochemistry were used to investigate tissues for the expression of TLR2,
      TLR4, TLR7, their downstream signaling components, MyD88 and TRIF, and associated
      cytokines, interferon (IFN)-gamma, tumor necrosis factor (TNF)-alpha, interleukin
      (IL)-4, and IL-10. RESULTS: TLR2, TLR4, TLR7, and IL-4 were significantly
      increased in CRSwNP patients when compared with either CRSsNP patients or control
      subjects, whereas TLR4 and TLR7, and downstream MyD88 were significantly
      decreased in CRSsNP patients versus patients from CRSwNP and control subjects.

PMID- 23157228
TI  - Proteomic analysis on N, N'-dinitrosopiperazine-mediated metastasis of
      nasopharyngeal carcinoma 6-10B cells.
AB  - BACKGROUND: Nasopharyngeal carcinoma (NPC) has a high metastatic feature. N,N'
      Dinitrosopiperazine (DNP) is involved in NPC metastasis, but its mechanism is not
      clear. The aim of this study is to reveal the pathogenesis of DNP-involved
      metastasis. 6-10B cells with low metastasis are from NPC cell line SUNE-1, were
      used to investigate the mechanism of DNP-mediated NPC metastasis. RESULTS: 6-10B
      cells were grown in DMEM containing 2H4-L-lysine and 13C 6 15 N4-L-arginine or
      conventional L-lysine and L-arginine, and identified the incorporation of amino
      acid by matrix-assisted laser desorption/ionization time-of-flight mass
      spectrometry. Labeled 6-10B cells were treated with DNP at 0 -18 MUM to establish
      the non-cytotoxic concentration (NCC) range. NCC was 0 -10 MUM. Following
      treatment with DNP at this range, the motility and invasion of cells were
      detected in vitro, and DNP-mediated metastasis was confirmed in the nude mice.
      DNP increased 6-10B cell metastasis in vitro and vivo. DNP-induced protein
      expression was investigated using a quantitative proteomic. The SILAC-based
      approach quantified 2698 proteins, 371 of which showed significant change after
      DNP treatment (172 up-regulated and 199 down-regulated proteins). DNP induced the
      change in abundance of mitochondrial proteins, mediated the status of oxidative
      stress and the imbalance of redox state, increased cytoskeletal protein,
      cathepsin, anterior gradient-2, and clusterin expression. DNP also increased the
      expression of secretory AKR1B10, cathepsin B and clusterin 6-10B cells. Gene
      Ontology and Ingenuity Pathway analysis showed that DNP may regulate protein
      synthesis, cellular movement, lipid metabolism, molecular transport, cellular
      growth and proliferation signaling pathways. CONCLUSION: DNP may regulate
      cytoskeletal protein, cathepsin, anterior gradient-2, and clusterin expression,
      increase NPC cells motility and invasion, is involved NPC metastasis.

PMID- 23157231
TI  - Progesterone attenuates several hippocampal abnormalities of the Wobbler mouse.
AB  - It is now recognised that progesterone plays a protective role for diseases of
      the central nervous system. In the Wobbler mouse, a model of motoneurone
      degeneration, progesterone treatment prevents spinal cord neuropathology and
      clinical progression of the disease. However, neuropathological and functional
      abnormalities have also been discovered in the brain of Wobbler mice and patients
      with amyotrophic lateral sclerosis. The present study examined the hippocampus of
      control and afflicted Wobbler mice and the changes in response to progesterone
      treatment. Mice received either a single progesterone implant (20 mg for 18
      days). We found that the hippocampal pathology of the untreated Wobblers involved
      a decreased expression of brain-derived neurotrophic factor (BDNF) mRNA,
      decreased astrogliosis in the stratum lucidum, stratum radiatum and stratum
      lacunosum-moleculare, decreased doublecortin (DCX)-positive neuroblasts in the
      subgranular zone of the dentate gyrus and a decreased density of GABA
      immunoreactive hippocampal interneurones and granule cells of the dentate gyrus.
      Although progesterone did not change the normal parameters of control mice, it
      attenuated several hippocampal abnormalities in Wobblers. Thus, progesterone
      increased hippocampal BDNF mRNA expression, decreased glial fibrillary acidic
      protein-positive astrocytes and increased the number of GABAergic interneurones
      and granule cells. The number of DCX expressing neuroblasts and immature neurones
      remained impaired in both progesterone-treated and untreated Wobblers. In
      conclusion, progesterone treatment exerted beneficial effects on some aspects of
      hippocampal neuropathology, suggesting its neuroprotective role in the brain, in
      agreement with previous data obtained in the spinal cord of Wobbler mice.

PMID- 23157232
TI  - Drug discovery: a view through the looking glass.

PMID- 23157234
TI  - Interview with Future Medicinal Chemistry's US Senior Editor, Iwao Ojima.
      Interview by Issac Bruce.
AB  - Professor Iwao Ojima studied at the University of Tokyo (Japan) before being
      appointed as a Senior Research Fellow and Group Leader at the Sagami Institute of
      Chemical Research. He is now Director of the Institute of Chemical Biology and
      Drug Discovery at State University of New York (USA) and has been a visiting
      professor in European, North American and Asian academic institutions. Professor
      Ojima agreed to serve as the US Senior Editor of Future Medicinal Chemistry when
      it launched in 2009 and continues to provide his expertise to the journal.
      Professor Ojima spoke to Future Medicinal Chemistry about why medicinal chemistry
      is such an exciting field to work in, the state of the pharmaceutical industry,
      and what features and issues make this journal unique.

PMID- 23157235
TI  - How the science of personalized medicines will change the clinical management of
      patients in the pharmacy.

PMID- 23157236
TI  - Current trends in epigenetic drug discovery.
AB  - Epigenetics is a major field of biomedical research, and epigenetic drug
      discovery shows great promise for new drugs. The first epigenetic inhibitors are
      already approved for human treatment. Here, we review a number of case studies
      that cover different aspects of epigenetic drug discovery spanning from
      sequencing of epigenetic modifications, assays development over screening to
      medicinal chemistry, in vivo testing and clinical application.

PMID- 23157237
TI  - Graphs and networks in chemical and biological informatics: past, present and
      future.
AB  - Chemical and biological network analysis has recently garnered intense interest
      from the perspective of drug design and discovery. While graph theoretic concepts
      have a long history in chemistry - predating quantum mechanics - and graphical
      measures of chemical structures date back to the 1970s, it is only recently with
      the advent of public repositories of information and availability of high
      throughput assays and computational resources that network analysis of large
      scale chemical networks, such as protein-protein interaction networks, has become
      possible. Drug design and discovery are undergoing a paradigm shift, from the
      notion of 'one target, one drug' to a much more nuanced view that relies on
      multiple sources of information: genomic, proteomic, metabolomic and so on. This
      holistic view of drug design is an incredibly daunting undertaking still very
      much in its infancy. Here, we focus on current developments in graph- and network
      centric approaches in chemical and biological informatics, with particular
      reference to applications in the fields of SAR modeling and drug design. Key
      insights from the past suggest a path forward via visualization and fusion of
      multiple sources of chemical network data.

PMID- 23157240
TI  - Indole molecules as inhibitors of tubulin polymerization: potential new
      anticancer agents.
AB  - Agents that interfere with tubulin function have a broad anti-tumor spectrum and
      they represent one of the most significant classes of anticancer agents. In the
      past few years, several small synthetic molecules that have an indole nucleus as
      a core structure have been identified as tubulin inhibitors. Among these, several
      aroylindoles, arylthioindoles, diarylindoles and indolylglyoxyamides have shown
      good inhibition towards the tubulin polymerization. This article reviews the
      synthesis, biological activities and SARs of these main classes of indoles. Brief
      mention has also been made about the fused indole analogs as tubulin inhibitors.

PMID- 23157238
TI  - Potent 19-norvitamin D analogs for prostate and liver cancer therapy.
AB  - The active form of vitamin D(3), 1alpha,25(OH)(2)D(3) or calcitriol, is known to
      inhibit the proliferation and invasiveness of many types of cancer cells,
      including prostate and liver cancer cells. These findings support the use of
      1alpha,25(OH)(2)D(3) for prostate and liver cancer therapy. However,
      1alpha,25(OH)(2)D(3) can cause hypercalcemia, thus, analogs of
      1alpha,25(OH)(2)D(3) that are less calcemic but exhibit potent antiproliferative
      activity would be attractive as therapeutic agents. We have developed 2alpha
      functional group substituted 19-norvitamin D(3) analogs with and without 14
      epimerization. Among them, 2alpha- and 2beta-(3-hydroxypropyl)-1alpha,25
      dihydroxy-19-norvitamin D(3) (MART-10 and -11, respectively) and 14-epi-2alpha-
      and 14-epi-2beta-(3-hydroxypropyl)-1alpha,25-dihydroxy-19-norvitamin D(3) (14-epi
      MART-10 and 14-epi-MART-11, respectively) were found to be the most promising. In
      this review, we discuss the synthesis of this unique class of vitamin D analogs,
      the molecular mechanism of anticancer actions of vitamin D, and the biological
      evaluation of these analogs for potential application to the prevention and
      treatment of prostate and liver cancer.

PMID- 23157242
TI  - Telomerase gene mutation screening and telomere overhang detection in Chinese
      patients with acute myeloid leukemia.
AB  - Loss-of-function mutations in telomerase complex genes reduce telomerase
      activity, and can clinically manifest as bone marrow failure disease, which
      predisposes to acute myeloid leukemia (AML). Telomerase dysfunction also leads to
      short telomeric overhang, which is a crucial telomeric structural component, and
      potentially results in chromosome instability. We screened variants in telomerase
      reverse transcriptase (TERT) and telomerase RNA component (TERC) genes, and
      investigated the 3'-overhang length in bone marrow samples from 72 Chinese
      patients with AML (61 de novo, 11 secondary, excluding M3), aged 13-77.
      Cytogenetics, disease severity and short-term survival were evaluated. Three TERT
      mutations (n896G>A, n1079C>G and n1451G>C) were identified. Mutation carriers had
      short overhangs and a poor prognosis. We found that overhang lengths were much
      shorter in AML compared to normal controls (p < 0.001). Short overhangs were
      related to a high percentage of karyotype abnormalities and poor prognosis (73.8%
      in short overhang group vs. 30% in normal group, p=0.001). Multivariant analysis
      showed that overhang length, age and unfavorable chromosome abnormalities served
      as independent prognostic markers in AML (Cox regression, p=0.001). These data
      raise the possibility that short overhang length may predict poor prognosis in
      patients with AML. These findings would have to be confirmed in large,
      prospective studies.

PMID- 23157239
TI  - SMN-inducing compounds for the treatment of spinal muscular atrophy.
AB  - Spinal muscular atrophy (SMA) is a leading genetic cause of infant mortality. A
      neurodegenerative disease, it is caused by loss of SMN1, although low, but
      essential, levels of SMN protein are produced by the nearly identical gene SMN2.
      While no effective treatment or therapy currently exists, a new wave of
      therapeutics has rapidly progressed from cell-based and preclinical animal models
      to the point where clinical trials have initiated for SMA-specific compounds.
      There are several reasons why SMA has moved relatively rapidly towards novel
      therapeutics, including: SMA is monogenic; the molecular understanding of SMN
      gene regulation has been building for nearly 20 years; and all SMA patients
      retain one or more copies of SMN2 that produces low levels of full-length, fully
      functional SMN protein. This review primarily focuses upon the biology behind the
      disease and examines SMN1- and SMN2-targeted therapeutics.

PMID- 23157243
TI  - Optimizing treatment for Parkinson's disease.

PMID- 23157244
TI  - Asymmetric blepharospasm with bilateral curtain sign.

PMID- 23157245
TI  - Seroconversion of neuromyelitis optica spectrum disorder with hyperCKemia: a case
      report.

PMID- 23157246
TI  - Opsoclonus, limbic encephalitis, anti-Ma2 antibodies and gastric adenocarcinoma.

PMID- 23157248
TI  - MicroRNA-140 expression during chondrogenic differentiation of equine cord blood
      derived mesenchymal stromal cells.
AB  - MicroRNAs are a class of short noncoding RNAs that are involved in various
      biological processes, including differentiation. MicroRNA-140 (miR-140) has been
      identified as a cartilage-specific microRNA with several targets involved in
      cartilage development and homeostasis. The aim of this study was to investigate
      the expression of miR-140 during chondrogenic differentiation of equine cord
      blood-derived mesenchymal stromal cells (eCB-MSCs). We demonstrate both that miR
      140 is highly expressed in normal equine articular cartilage and that eCB-MSCs
      express significantly higher levels of this microRNA after 14 days of
      chondrogenic differentiation. Furthermore, miR-140 expression closely paralleled
      that of the cartilage-specific transcription factor Sox9, suggesting that miR-140
      may be under the transcriptional regulation of Sox9 in these cells. The
      expression patterns of miR-140 targets the chemokine (CXC motif) ligand 12
      (CXCL12), A disintegrin and metalloproteinase with thrombosponin motifs (ADAMTS)
      5 and insulin growth factor binding protein 5 (IGFBP5) were also determined;
      however, only CXCL12 and ADAMTS-5 were repressed while miR-140 expression was
      upregulated. Together, these studies suggest that miR-140 is an important
      regulator of cartilage development and homeostasis in eCB-MSCs that may act, in
      part, through the regulation of CXCL12 and ADAMTS-5.

PMID- 23157249
TI  - Reaction of 13-vertex carborane MU-1,2-(CH2)3-1,2-C2B11H11 with nucleophiles:
      scope and mechanism.
AB  - 13-Vertex carborane, MU-1,2-(CH(2))(3)-1,2-C(2)B(11)H(11) (1), reacted with a
      series of nucleophiles (Nu) to give the cage carbon extrusion products [MU-1,2
      (CH(2))(3)CH(Nu)-1-CB(11)H(10)](-), [MU-1,2-(CH(2))(2)CH(Nu)CH(2)-1-CB(11)H(10)](
      ), and/or [MU-1,2-(CH(2))(2)CH?CH-1-CB(11)H(10)](-), depending on the nature of
      Nu and the reaction conditions. The key intermediates for the formation of
      CB(11)(-) anions were isolated and structurally characterized as [MU-eta:eta:eta
      7,8,10-(CH(2))(3)CHB(Nu)-7-CB(10)H(10)](-) (Nu = OMe, NEt(2)). The reaction
      mechanism is thus proposed, which involves the attack of Nu at the most electron
      deficient cage boron, followed by H-migration to one of the cage carbons, leading
      to the formation of the intermediate. Nu-migration gives the products.

PMID- 23157250
TI  - Cost-effective diagnosis of male oxidative stress using the nitroblue tetrazolium
      test: useful application for the developing world.
AB  - Seminal oxidative stress plays an important role in male factor infertility
      (MFI), worldwide. A study was thus undertaken for the first time to establish
      seminal reactive oxygen species (ROS) as a clinical marker of MFI in a cohort of
      Sri Lankan males. The nitro blue tetrazolium (NBT) assay for ROS estimation and
      modified Endtz test for detecting leucocytes were carried out on semen samples (N
      = 102) of subfertile males. Age-matched individuals (N = 30) with proven past
      paternity served as controls. Significantly higher ROS production was evident in
      individuals with asthenozoospermia and unexplained infertility (Mann-Whitney U
      test, P = 0.000), than in the fertile and the other subfertile groups tested.
      Receiver operating characteristic plot analysis established cut-off points of
      40.57 and 42.02 MUg formazan/10(7) spermatozoa for ROS to distinguish fertile
      males from asthenozoospermics (71.4% sensitivity: 70% specificity; AUC = 0.82),
      and from unexplained infertile males (74.1 % sensitivity: 73.3% specificity; AUC
      = 0.85) respectively. As ROS appear to be a potential marker of male infertility,
      it is imperative to validate this test as a simple, cost-effective hence a widely
      accessible diagnostic tool to be included in MFI investigations in the developing
      world.

PMID- 23157251
TI  - Variants in the 17q21 asthma susceptibility locus are associated with allergic
      rhinitis in the Japanese population.
AB  - BACKGROUND: Allergic rhinitis (AR) is a very common disorder peaking in the
      teenage years that is mediated by hypersensitivity responses to environmental
      allergens. Although it is well established that the ORMDL3 locus at chromosome
      17q21 is associated with susceptibility to bronchial asthma, the genetic
      influences of the polymorphisms of the locus in allergic rhinitis are unclear.
      OBJECTIVE: To examine whether the polymorphisms in the 17q21 asthma
      susceptibility locus are associated with allergic rhinitis in the Japanese
      population. METHODS: We performed linkage disequilibrium (LD) mapping of the
      locus using the HapMap database and conducted an association study of the locus
      with a total of 15 tag SNPs in two independent populations. We further evaluated
      correlations of genotypes with changes in expression of genes at the region in
      lymphoblastoid cell lines in the Japanese population and assessed the expression
      levels of the genes in nasal epithelium and various human tissues. RESULTS: We
      found a significant association between a total of five polymorphisms in the
      17q21 asthma susceptibility locus, rs9303277, rs7216389, rs7224129, rs3744246,
      and rs4794820, and AR (minimum P(combined)  = 0.00074, rs4794820). The expression
      level of the ORMDL3 transcript was significantly correlated with the genotype of
      rs12150079, rs7216389, rs3744246, and rs4794820 with P < 0.01 (minimum P =
      0.0058, rs7216389), and ORMDL3 mRNA was highly expressed in nasal epithelium.
      CONCLUSION: Genetic variants in the 17q21 asthma susceptibility locus are
      significantly associated with AR in the Japanese population.

PMID- 23157253
TI  - Blood glucose levels in children with Type 1 diabetes attending a residential
      diabetes camp: a 2-year review.
AB  - AIMS: The objective of this retrospective analysis of blood glucose values at a
      week-long residential summer camp for children with Type 1 diabetes was to
      provide experiential data to reinforce current summer camp guidelines and to
      determine if specific interventions implemented between 2009 and 2010 were
      effective in lowering average blood glucose among our campers without increasing
      risk of hypoglycaemia. METHODS: Blood glucose records were obtained from a random
      selection of children who attended six 1-week camp sessions, three each in 2009
      and 2010. Five values per day: pre-meal breakfast, lunch and dinner, pre-evening
      snack and midnight values were analysed. RESULTS: A total of 13,267 blood glucose
      values were included. There were no severe hypoglycaemic episodes, seizures or
      need for full-dose glucagon or intravenous glucose in either year. Mean blood
      glucose was significantly lower in 2010 compared with 2009 (9.22 vs. 10.06
      mmol/l, P < 0.001). Older age and camp year were associated with lower mean blood
      glucose, even when controlling for gender and duration of diabetes. CONCLUSIONS:
      This analysis is the largest so far conducted at a residential diabetes camp.
      Mean blood glucose levels were lower than other published studies. Although we
      cannot attribute a cause-and-effect relationship between our interventions and
      the improvement in blood glucose between 2009 and 2010, the use of pre-meal
      insulin bolus doses, low glycaemic meals and highlighting blood glucose levels in
      logs before being reviewed by endocrinologists are strongly encouraged. From this
      study we hope to establish benchmarks for comparison among camps and begin to
      identify best practices.

PMID- 23157254
TI  - Transmembrane electric potential difference in the protein-pigment complex of
      photosystem 2.
AB  - The protein-pigment complex of photosystem 2 (PS2) localized in the thylakoid
      membranes of higher plants, algae, and cyanobacteria is the main source of oxygen
      on Earth. The light-induced functioning of PS2 is directly linked to electron and
      proton transfer across the membrane, which results in the formation of
      transmembrane electric potential difference (DeltaPsi). The major contribution to
      DeltaPsi of the PS2 reaction center is due to charge separation between the
      primary chlorophyll donor P(680) and the quinone acceptor Q(A), accompanied by re
      reduction of P(680)(+) by the redox-active tyrosine residue Y(Z). The processes
      associated with the uptake and release of protons on the acceptor and donor sides
      of the enzyme, respectively, are also coupled with DeltaPsi generation. The
      objective of this work was to describe the mechanisms of DeltaPsi generation
      associated with the S-state transitions of the water-oxidizing complex in intact
      PS2 complex and in PS2 preparation depleted of Mn(4)Ca cluster in the presence of
      artificial electron donors. The findings elucidate the mechanisms of electrogenic
      reactions on the PS2 donor side and may be a basis for development of an
      effective solar energy conversion system.

PMID- 23157252
TI  - Tetarimycin A, an MRSA-active antibiotic identified through induced expression of
      environmental DNA gene clusters.
AB  - The propagation of DNA extracted directly from environmental samples in
      laboratory-grown bacteria provides a means to study natural products encoded in
      the genomes of uncultured bacteria. However, gene silencing often hampers the
      functional characterization of gene clusters captured on environmental DNA
      clones. Here we show that the overexpression of transcription factors found in
      sequenced environmental DNA-derived biosynthetic gene clusters, in conjunction
      with traditional culture-broth extract screening, can be used to identify new
      bioactive secondary metabolites from otherwise-silent gene clusters. Tetarimycin
      A, a tetracyclic methicillin-resistant  Staphylococcus aureus  (MRSA)-active
      antibiotic, was isolated from the culture-broth extract of  Streptomyces albus 
      cultures cotransformed with an environmentally derived type-II polyketide
      biosynthetic gene cluster and its pathway-specific  Streptomyces  antibiotic
      regulatory protein (SARP) cloned under the control of the constitutive ermE*
      promoter.

PMID- 23157255
TI  - Energetic and regulatory role of proton potential in chloroplasts.
AB  - The review focuses on the energetic and regulatory role of proton potential in
      the activity of chloroplasts, the light energy-converting organelles of plant
      cells. Mechanisms of generation of the transmembrane difference of
      electrochemical potentials of hydrogen ions (Deltau(~)(H+)) in the chloroplast
      thylakoid membranes are considered. Methods for measuring the intrathylakoid pH
      in chloroplasts are described. It is shown that under conditions of
      phosphorylation in chloroplasts, the pH of the intrathylakoid space decreases
      moderately (pH(in) >= 6.0-6.2, at the stroma pH(out) ~ 7.8-8.0), with a
      corresponding concentration component of Deltau(~)(H+) equal to DeltapH <= 1.6
      2.0. On analyzing the energy and structural features of ATP synthase of
      chloroplasts, we conclude that the energy stored as the concentration component
      of the proton potential DeltapH is sufficient to sustain ATP synthesis. The
      mechanisms of pH-dependent regulation of electron transport in chloroplasts
      (photosynthetic control of electron transport, enhancement of non-photochemical
      quenching of chlorophyll excitation in the light-harvesting antenna, light
      induced activation of the Calvin-Benson cycle reactions, activation of ATP
      synthase) are considered briefly.

PMID- 23157256
TI  - Boronated derivatives of chlorin e(6) and fluoride-containing porphyrins as
      penetrating anions: a study using bilayer lipid membranes.
AB  - Boronated derivatives of porphyrins are studied extensively as promising
      compounds for boron-neutron capture therapy and photodynamic therapy.
      Understanding of the mechanism of their permeation across cell membranes is a key
      step in screening for the most efficient compounds. In the present work, we
      studied the ability of boronated derivatives of chlorin e(6) and porphyrins,
      which are mono-, di-, and tetra-anions, to permeate through planar bilayer lipid
      membranes (BLM). The translocation rate constants through the hydrophobic part of
      the lipid bilayer were estimated for monocarborane and its conjugate with chlorin
      e(6) by the method of electrical current relaxation. They were similar, 6.6 and
      6.8 sec(-1), respectively. Conjugates of porphyrins carrying two and four
      carborane groups were shown to permeate efficiently through a BLM although they
      carry two charges and four charges, respectively. The rate of permeation of the
      tetraanion estimated by the BLM current had superlinear dependence on the BLM
      voltage. Because the resting potential of most mammalian cells is negative
      inside, it can be concluded that the presence of negatively-charged boronated
      groups in compounds should hinder the accumulation of the porphyrins in cells.

PMID- 23157257
TI  - Novel mitochondria-targeted compounds composed of natural constituents:
      conjugates of plant alkaloids berberine and palmatine with plastoquinone.
AB  - Novel mitochondria-targeted compounds composed entirely of natural constituents
      have been synthesized and tested in model lipid membranes, in isolated
      mitochondria, and in living human cells in culture. Berberine and palmatine,
      penetrating cations of plant origin, were conjugated by nonyloxycarbonylmethyl
      residue with the plant electron carrier and antioxidant plastoquinone. These
      conjugates (SkQBerb, SkQPalm) and their analogs lacking the plastoquinol moiety
      (C10Berb and C10Palm) penetrated across planar bilayer phospholipid membrane in
      their cationic forms and accumulated in isolated mitochondria or in mitochondria
      in living human cells in culture. Reduced forms of SkQBerb and SkQPalm inhibited
      lipid peroxidation in isolated mitochondria at nanomolar concentrations. In
      isolated mitochondria and in living cells, the berberine and palmatine moieties
      were not reduced, so antioxidant activity belonged exclusively to the
      plastoquinol moiety. In human fibroblasts, nanomolar SkQBerb and SkQPalm
      prevented fragmentation of mitochondria and apoptosis induced by exogenous
      hydrogen peroxide. At higher concentrations, conjugates of berberine and
      palmatine induced proton transport mediated by free fatty acids both in model and
      in mitochondrial membrane. In mitochondria this process was facilitated by the
      adenine nucleotide carrier. As an example of application of the novel
      mitochondria-targeted antioxidants SkQBerb and SkQPalm to studies of signal
      transduction, we discuss induction of cell cycle arrest, differentiation, and
      morphological normalization of some tumor cells. We suggest that production of
      oxygen radicals in mitochondria is necessary for growth factors-MAP-kinase
      signaling, which supports proliferation and transformed phenotype.

PMID- 23157258
TI  - Mitochondria-targeted plastoquinone antioxidant SkQR1 decreases trauma-induced
      neurological deficit in rat.
AB  - A protective effect of a mitochondria-targeted antioxidant, a cationic rhodamine
      derivative linked to a plastoquinone molecule (10-(6'
      plastoquinonyl)decylrhodamine-19, SkQR1) was studied in the model of open focal
      trauma of rat brain sensorimotor cortex. It was found that daily intraperitoneal
      injections of SkQR1 (100 nmol/kg) for 4 days after the trauma improved
      performance in a test characterizing neurological deficit and decreased the
      volume of the damaged cortical area. Our results suggest that SkQR1 exhibits
      profound neuroprotective effect, which may be explained by its antioxidative
      activity.

PMID- 23157259
TI  - Oxidative phosphorylation and respiratory control phenomenon in Paracoccus
      denitrificans plasma membrane.
AB  - Changes in respiratory activity, transmembrane electric potential, and ATP
      synthesis as induced by additions of limited amounts of ADP and P(i) to tightly
      coupled inverted (inside-out) Paracoccus denitrificans plasma membrane vesicles
      were traced. The pattern of the changes was qualitatively the same as those
      observed for coupled mitochondria during the classical State 4-State 3-State 4
      transition. Bacterial vesicles devoid of energy-dependent permeability barriers
      for the substrates of oxidation and phosphorylation were used as a simple
      experimental model to investigate two possible mechanisms of respiratory control:
      (i) in State 4 phosphoryl transfer potential (ATP/ADP * P(i)) is equilibrated
      with proton-motive force by reversibly operating F(1).F(o)-ATPase (thermodynamic
      control); (ii) in State 4 apparent "equilibrium" is reached by unidirectional
      operation of proton motive force-activated F(1).F(o)-ATP synthase. The data
      support the kinetic mechanism of the respiratory control phenomenon.

PMID- 23157260
TI  - On the photocycle of 4-ketobacteriorhodopsin.
AB  - The artificial pigment 4-ketobacteriorhodopsin is an interesting analog of
      bacteriorhodopsin. Arguments concerning the scheme of the photocycle of 4
      ketobacteriorhodopsin are discussed.

PMID- 23157261
TI  - Primary steps of electron and energy transfer in photosystem I: effect of
      excitation pulse wavelength.
AB  - Time-resolved differential spectra of photosystem I complex were obtained by the
      "pump-probe" technique with 25-fs pulses with maxima at 670, 700, and 720 nm. The
      ratio between the number of excited chlorophyll molecules of the antenna and of
      the reaction center was shown to depend on spectral characteristics of the pump
      pulses. In all cases, an ultrafast (<150 fs) formation of the primary radical
      pair P700(+)A(0)(?) was recorded. However, on excitation by pulses with maxima at
      670 or 700 nm, detection of the charge separation was masked by the much more
      intensive bleaching at the chlorophyll Q(y) band due to excitation of the bulk
      antenna chlorophylls. We show that triggering the charge separation by 25-fs
      pulses centered at 720 nm allows to detect more clearly kinetics of formation of
      the primary and secondary ion-radical pairs. The findings help to explain
      possible reasons for discrepancies of kinetics of primary steps of electron
      transfer detected in different laboratories.

PMID- 23157262
TI  - Interaction of tetraphenylphosphonium and dodecyltriphenylphosphonium with lipid
      membranes and mitochondria.
AB  - The permeability of a planar lipid membrane (composed of
      diphytanoylphosphatidylcholine) for tetraphenylphosphonium (TPP) was
      investigated. The observed level of the diffusion potential generated as a
      function of the TPP concentration gradient differed from the theoretically
      expected value, possibly due to proton leakage of the membrane mediated by the
      traces of fatty acids in the phospholipid forming the membrane. Using the
      molecular dynamics approach to study movement of TPP and
      dodecyltriphenylphosphonium (C(12)TPP) with different affinity to the lipid
      bilayer through a bilayer lipid membrane, it was found that C(12)TPP has a
      greater affinity to the membrane surface than TPP. However, the two cations have
      the same activation energy for transmembrane transfer. Interaction of TPP and
      C(12)TPP with tightly-coupled mitochondria from the yeast Yarrowia lipolytica was
      also investigated. At low, micromolar concentrations, both cations are
      "relatively weak, mild uncouplers", do not shunt electron transfer along the
      respiratory chain, do not disturb (damage) the inner mitochondrial membrane, and
      profoundly promote the uncoupling effect of fatty acids. At higher concentrations
      they inhibit respiration in state 3, and at much higher concentrations they
      induce swelling of mitochondria, possibly due to their detergent action.

PMID- 23157263
TI  - Mild uncoupling of respiration and phosphorylation as a mechanism providing
      nephro- and neuroprotective effects of penetrating cations of the SkQ family.
AB  - It is generally accepted that mitochondrial production of reactive oxygen species
      is nonlinearly related to the value of the mitochondrial membrane potential with
      significant increment at values exceeding 150 mV. Due to this, high values of the
      membrane potential are highly dangerous, specifically under pathological
      conditions associated with oxidative stress. Mild uncoupling of oxidative
      phosphorylation is an approach to preventing hyperpolarization of the
      mitochondrial membrane. We confirmed data obtained earlier in our group that
      dodecylrhodamine 19 (C(12)R1) (a penetrating cation from SkQ family not
      possessing a plastoquinone group) has uncoupling properties, this fact making it
      highly potent for use in prevention of pathologies associated with oxidative
      stress induced by mitochondrial hyperpolarization. Further experiments showed
      that C(12)R1 provided nephroprotection under ischemia/reperfusion of the kidney
      as well as under rhabdomyolysis through diminishing of renal dysfunction
      manifested by elevated level of blood creatinine and urea. Similar
      nephroprotective properties were observed for low doses (275 nmol/kg) of the
      conventional uncoupler 2,4-dinitrophenol. Another penetrating cation that did not
      demonstrate protonophorous activity (SkQR4) had no effect on renal dysfunction.
      In experiments with induced ischemic stroke, C(12)R1 did not have any effect on
      the area of ischemic damage, but it significantly lowered neurological deficit.
      We conclude that beneficial effects of penetrating cation derivatives of
      rhodamine 19 in renal pathologies and brain ischemia may be at least partially
      explained by uncoupling of oxidation and phosphorylation.

PMID- 23157264
TI  - Substitution of ether linkage for ester bond in phospholipids increases
      permeability of bilayer lipid membrane for SkQ1-type penetrating cations.
AB  - Using dialkylphospholipid (diphytanyl phosphatidylcholine) instead of the
      conventional diacylphospholipid (diphytanoyl phosphatidylcholine) in planar lipid
      bilayer membranes (BLM) led to an increase in the diffusion potential of the
      penetrating cation plastoquinonyl-decyl-triphenylphosphonium (SkQ1), making it
      close to the Nernst value, and accelerated translocation of SkQ1 across the BLM
      as monitored by the kinetics of a decrease in the transmembrane electric current
      after applying a voltage (current relaxation). The consequences of changing from
      an ester to an ether linkage between the head groups and the hydrocarbon chains
      are associated with a substantial reduction in the membrane dipole potential
      known to originate from dipoles of tightly bound water molecules and carbonyl
      groups in ester bonds. The difference in the dipole potential between BLM formed
      of the ester phospholipid and that of the ether phospholipid was estimated to be
      100 mV. In the latter case, suppression of SkQ1-mediated proton conductivity of
      the BLM was also observed.

PMID- 23157265
TI  - Signaling pathways in tumor vasculogenic mimicry.
AB  - Solid tumor growth is dependent on the development of an adequate blood supply.
      For years, sprouting angiogenesis has been considered as the exclusive mechanism
      of tumor vascularization. However, in recent years, another mechanism of tumor
      vascularization has been identified that does not involve endothelial cells, a
      process called vasculogenic mimicry (VM). VM describes the unique ability of
      highly aggressive tumor cells to form vessel-like networks by virtue of their
      high plasticity. VM has been observed in several tumor types, and its occurrence
      is strongly associated with poor prognosis. This review focuses on signaling
      molecules and cascades involved in VM. In addition, the clinical significance of
      VM regardless of anti-angiogenesis treatment modalities is described.

PMID- 23157266
TI  - Organization of chloroplast psbA-trnH intergenic spacer in dicotyledonous
      angiosperms of the family Umbelliferae.
AB  - Chloroplast intergenic psbA-trnH spacer has recently become a popular tool in
      plant molecular phylogenetic studies at low taxonomic level and as suitable for
      DNA barcoding studies. In present work, we studied the organization of psbA-trnH
      in the large family Umbelliferae and its potential as a DNA barcode and
      phylogenetic marker in this family. Organization of the spacer in Umbelliferae is
      consistent with a general pattern evident for angiosperms. The 5'-region of the
      spacer situated directly after the psbA gene is more conserved in length compared
      to the 3'-region, which has greater sequence variation. This pattern can be
      attributed to the maintenance of the secondary structural elements in the 5'
      region of the spacer needed for posttranscriptional regulation of psbA gene
      expression. In Umbelliferae only, the conserved region contains a duplication of
      the fragment corresponding to the loop of the stem-loop structure and an
      independent appearance of identical sequence complementarities (traits) necessary
      to stabilize the stem-loop structure in different lineages. The 3'-region of the
      spacer nearest to trnH ranges greatly in size, mainly due to deletions, and the
      decrease in spacer length is a general trend in the evolution psbA-trnH in
      Umbelliferae. The features revealed in spacer organization allow us to use it as
      phylogenetic marker, and indels seem to be more informative for analyses than
      nucleotide substitutions. However, high conservation among closely related taxa
      and occurrence of homoplastic inversions in the stem-loop structure limit its
      application as DNA barcode.

PMID- 23157267
TI  - Separation and study of the range of plasminogen isoforms in patients with
      prostate cancer.
AB  - Using affinity chromatography, two-dimensional electrophoresis, and MALDI-TOF
      mass spectrometry, plasminogen isoforms were separated and identified in blood
      plasma. Healthy donors and patients with prostate cancer in various stages of
      development were included in the studied sample. With the development of prostate
      cancer, four additional specific plasminogen isoforms are registered in blood
      plasma; they are characterized by lower molecular weights and higher pI values
      compared to isoforms found in the control group.

PMID- 23157268
TI  - In vitro phosphorylation of the N-terminal half of hordeivirus movement protein.
AB  - The N-terminal half of TGB1 movement protein of poa semilatent hordeivirus, which
      forms a ribonucleoprotein complex involved in movement of the viral genome in the
      plant, and its two domains, NTD and ID, are phosphorylated in vitro by a fraction
      enriched in cell walls from Nicotiana benthamiana. Using a set of protein kinase
      inhibitors with different specificities, it was found that enzymes possessing
      activities of casein kinase 1, protein kinase A, and protein kinase C are
      involved in phosphorylation. Commercial preparations of protein kinases A and C
      are able to phosphorylate in vitro recombinant proteins corresponding to the N
      terminal half of the protein and its domains NTD and ID. Phosphorylation of the
      NTD has no effect on the efficiency and character of its binding to RNA. However,
      phosphorylation of the ID leads to a decrease in its RNA-binding activity and in
      the ability for homological protein-protein interactions.

PMID- 23157269
TI  - Improving liquid-crystal-based biosensing in aqueous phases.
AB  - Liquid crystal (LC)-based biological sensors permit the study of aqueous
      biological samples without the need for the labeling of biological species with
      fluorescent dyes (which can be laborious and change the properties of the
      biological sample under study). To date, studies of LC-based biosensors have
      explored only a narrow range of the liquid crystal/alignment layer combinations
      essential to their operation. Here, we report a study of the role of LC elastic
      constants and the surface anchoring energy in determining the sensitivity of LC
      based biosensors. By investigating a mixture of rod-shape and bent-shape
      mesogens, and three different alignment layers, we were able to widen the useful
      detection range of a LC-based sensor by providing an almost-linear mapping of
      effective birefringence with anionic surfactant concentrations between 0.05 mM
      and 1 mM (model target analyte). These studies pave the way for optimization of
      LC-based biosensors and reveal the importance of the choice of both the LC
      material and the alignment layer in determining sensor properties.

PMID- 23157270
TI  - Non-fouling hydrogels of 2-hydroxyethyl methacrylate and zwitterionic
      carboxybetaine (meth)acrylamides.
AB  - Five poly(betaine) brushes were prepared, and their resistance to blood plasma
      fouling was studied. Two carboxybetaines monomers were copolymerized with 2
      hydroxyethyl methacrylate (HEMA) to prepare novel hydrogels. By increasing the
      content of the zwitterionic comonomer, a 4-fold increase in the water content
      could be achieved while retaining mechanical properties close to the widely used
      poly(HEMA) hydrogels. All hydrogels showed an unprecedentedly low fouling from
      blood plasma. Remarkably, by copolymerization with 10 mol % of carboxybetaine
      acrylamide, hydrogels fully resistant to blood plasma were prepared.

PMID- 23157271
TI  - Prognostic significance of vascular endothelial growth factor expression in adult
      patients with acute myeloid leukemia: a meta-analysis.
AB  - The prognostic significance of angiogenic markers remains controversial. Many
      studies have suggested that vascular endothelial growth factor (VEGF) or vascular
      endothelial growth factor receptor (VEGFR) overexpression correlates with poorer
      survival in adult patients with acute myeloid leukemia (AML), but some studies
      suggest a greater probability of survival. To investigate the prognostic
      significance of VEGF overexpression in adult AML, we performed a meta-analysis of
      the published studies that provided survival information according to VEGF
      expression status. Pooled hazard ratios (HRs) indicated that VEGF overexpression
      had a poor impact on the survival of adult patients with AML. The combined hazard
      ratio for event-free survival (EFS) was 1.40 and summary HR for overall survival
      was 1.54. The pooled HR was 1.92 in AML by enzyme-linked immunosorbent assay and
      1.67 in AML by immunohistochemistry. These findings indicate that VEGF
      overexpression has an adverse impact on prognosis for patients with AML. VEGF may
      become a useful prognostic factor in the context of targeted therapy for patients
      with adult AML.

PMID- 23157272
TI  - Improving protein coreference resolution by simple semantic classification.
AB  - BACKGROUND: Current research has shown that major difficulties in event
      extraction for the biomedical domain are traceable to coreference. Therefore,
      coreference resolution is believed to be useful for improving event extraction.
      To address coreference resolution in molecular biology literature, the Protein
      Coreference (COREF) task was arranged in the BioNLP Shared Task (BioNLP-ST,
      hereafter) 2011, as a supporting task. However, the shared task results indicated
      that transferring coreference resolution methods developed for other domains to
      the biological domain was not a straight-forward task, due to the domain
      differences in the coreference phenomena. RESULTS: We analyzed the contribution
      of domain-specific information, including the information that indicates the
      protein type, in a rule-based protein coreference resolution system. In
      particular, the domain-specific information is encoded into semantic
      classification modules for which the output is used in different components of
      the coreference resolution. We compared our system with the top four systems in
      the BioNLP-ST 2011; surprisingly, we found that the minimal configuration had
      outperformed the best system in the BioNLP-ST 2011. Analysis of the experimental
      results revealed that semantic classification, using protein information, has
      contributed to an increase in performance by 2.3% on the test data, and 4.0% on
      the development data, in F-score. CONCLUSIONS: The use of domain-specific
      information in semantic classification is important for effective coreference
      resolution. Since it is difficult to transfer domain-specific information across
      different domains, we need to continue seek for methods to utilize such
      information in coreference resolution.

PMID- 23157273
TI  - Do mood and the receipt of work-based support influence nurse perceived quality
      of care delivery? A behavioural diary study.
AB  - AIMS AND OBJECTIVES: To examine the effect of nurse mood in the worst event of
      shift (negative affect, positive affect), receipt of work-based support from
      managers and colleagues, colleague and patient involvement on perceived quality
      of care delivery. BACKGROUND: While the effect of the work environment on nurse
      mood is well documented, little is known about the effects of the worst event of
      shift on the quality of care delivered by nurses. DESIGN: This behavioural diary
      study employed a within-subject and between-subject designs incorporating both
      cross-sectional and longitudinal elements. METHODS: One hundred and seventy-one
      nurses in four large district general hospitals in England completed end-of-shift
      computerised behavioural diaries over three shifts to explore the effects of the
      worst clinical incident of shift. Diaries measured negative affect, positive
      affect, colleague involvement, receipt of work-based support and perceived
      quality of care delivery. Analysis used multilevel modelling (MLWIN 2.19; Centre
      for Multi-level Modelling, University of Bristol, Bristol, UK). RESULTS: High
      levels of negative affect and low levels of positive affect reported in the worst
      clinical incident of shift were associated with reduced perceived quality of care
      delivery. Receipt of managerial support and its interaction with negative affect
      had no relationship with perceived quality of care delivery. Perceived quality of
      care delivery deteriorated the most when the nurse reported a combination of high
      negative affect and no receipt of colleague support in the worst clinical
      incident of shift. Perceived quality of care delivery was also particularly
      influenced when the nurse reported low positive affect and colleague actions
      contributed to the problem. CONCLUSIONS: Receipt of colleague support is
      particularly salient in protecting perceived quality of care delivery, especially
      if the nurse also reports high levels of negative affect in the worst event of
      shift. RELEVANCE TO CLINICAL PRACTICE: The effect of work-based support on care
      delivery is complex and requires further investigation.

PMID- 23157274
TI  - Modulation of endoplasmic reticulum calcium pump expression during lung cancer
      cell differentiation.
AB  - Cellular calcium signaling plays important roles in several signal transduction
      pathways that control proliferation, differentiation and apoptosis. In epithelial
      cells calcium signaling is initiated mainly by calcium release from endoplasmic
      reticulum-associated intracellular calcium pools. Because calcium is accumulated
      in the endoplasmic reticulum by sarco/endoplasmic reticulum calcium ATPases
      (SERCA), these enzymes play a critical role in the control of calcium-dependent
      cell activation, growth and survival. We investigated the modulation of SERCA
      expression and function in human lung adenocarcinoma cells. In addition to the
      ubiquitous SERCA2 enzyme, the SERCA3 isoform was also expressed at variable
      levels. SERCA3 expression was selectively enhanced during cell differentiation in
      lung cancer cells, and marked SERCA3 expression was found in fully differentiated
      normal bronchial epithelium. As studied by using a recombinant fluorescent
      calcium probe, induction of the expression of SERCA3, a lower calcium affinity
      pump, was associated with decreased intracellular calcium storage, whereas the
      amplitude of capacitative calcium influx remained unchanged. Our observations
      indicate that the calcium homeostasis of the endoplasmic reticulum in lung
      adenocarcinoma cells presents a functional defect due to decreased SERCA3
      expression that is corrected during pharmacologically induced differentiation.
      The data presented in this work show, for the first time, that endoplasmic
      reticulum calcium storage is anomalous in lung cancer cells, and suggest that
      SERCA3 may serve as a useful new phenotypic marker for the study of lung
      epithelial differentiation. 

PMID- 23157275
TI  - Psychosocial factors and chronic spontaneous urticaria: a systematic review.
AB  - BACKGROUND: Chronic spontaneous urticaria (CSU) is one of the most costly
      allergic conditions challenging physicians as well as patients and their
      families. Despite evident lacunae in the understanding of the pathogenesis, at
      least some findings suggest that psychosocial factors likely contribute to the
      development and exacerbation of CSU. We aim to assess the contribution of
      psychological factors to CSU. METHODS: Systematic search of PubMed and
      OVID/Medline databases was conducted from 1 January 1935 to 1 January 2012.
      Studies selected include original research in English, Spanish and French
      exploring the association between CSU and psychosocial factors. Two investigators
      independently reviewed all titles and abstracts to identify potentially relevant
      articles and resolved discrepancies by repeated review and discussion and
      arbitration of a third reviewer. Quality of systematic reviews and meta-analyses
      was assessed using a measure based on the Newcastle-Ottawa Scale and
      psychological conditions of CSU patients. RESULTS: We identified 114 eligible
      studies spanning 77 years and featuring 17 reviews, 67 studies related to neither
      CSU nor psychosocial factors, and eight studies that provided either no
      prevalence estimates or insufficient sample size. Pooling effect sizes using
      random effects, analyses revealed that, despite large heterogeneity (I(2) of
      97.60%), psychosocial factors had a prevalence of 46.09% (95% confidence
      interval, 44.01%, 48.08%). CONCLUSION: Future research needs to better establish
      the contribution of psychosocial factors to the pathogenesis and exacerbation of
      CSU, and explore the possible benefit of behavioural interventions to the
      development of new management strategies.

PMID- 23157276
TI  - Differentiating minimum clinically important difference for primary and revision
      lumbar fusion surgeries.
AB  - OBJECT: Previous studies have reported on the minimum clinically important
      difference (MCID), a threshold of improvement that is clinically relevant for
      lumbar degenerative disorders. Recent studies have shown that pre- and
      postoperative health-related quality of life (HRQOL) measures vary among patients
      with different diagnostic etiologies. There is also concern that a patient's
      previous care experience may affect his or her perception of clinical
      improvement. This study determined if MCID values for the Oswestry Disability
      Index (ODI), 36-Item Short-Form Health Survey (SF-36), and back and leg pain are
      different between patients undergoing primary or revision lumbar fusion. METHODS:
      Prospectively collected preoperative and 1-year postoperative patient-reported
      HRQOLs, including the ODI, SF-36 physical component summary (PCS), and numeric
      rating scales (0-10) for back and leg pain, in patients undergoing lumbar spine
      fusion were analyzed. Patients were grouped into either the primary surgery or
      revision group. As the most widely accepted MCID values were calculated from the
      minimum detectable change, this method was used to determine the MCID. RESULTS: A
      total of 722 patients underwent primary procedures and 333 patients underwent
      revisions. There was no statistically significant difference in demographics
      between the groups. Each group had a statistically significant improvement at 1
      year postoperatively compared with baseline. The minimum detectable change
      derived MCID values for the primary group were 1.16 for back pain, 1.36 for leg
      pain, 12.40 for ODI, and 5.21 for SF-36 PCS. The MCID values for the revision
      group were 1.21 for back pain, 1.28 for leg pain, 11.79 for ODI, and 4.90 for SF
      36 PCS. These values are very similar to those previously reported in the
      literature. CONCLUSIONS: The MCID values were similar for the revision and
      primary lumbar fusion groups, even when subgroup analysis was done for different
      diagnostic etiologies, simplifying interpretation of clinical improvement. The
      results of this study further validate the use of patient-reported HRQOLs to
      measure clinical effectiveness, as a patient's previous experience with care does
      not seem to substantially alter an individual's perception of clinical
      improvement.

PMID- 23157277
TI  - Is inclusion of the occiput necessary in fusion for C1-2 instability in
      rheumatoid arthritis?
AB  - OBJECT: The atlantoaxial joint is the location most and earliest affected in
      patients with rheumatoid arthritis (RA). In longstanding disease, ligamentous and
      osseous destruction can progress and involve all cervical segments. If surgical
      intervention is necessary, some prefer, to be safe, undertaking fusion to the
      occiput, whereas others advocate 1-level fusion of C1-2. Sparing the occiput (Oc)
      C1 segment would allow retention of a considerable amount of physiological range
      of motion and seems beneficial against subaxial overload. Previous clinical
      studies on this topic have provided only nonspecific data after short-term follow
      up, rendering a segment-sparing approach questionable. The purpose of the present
      investigation was to assess long-term progression of inflammatory or degenerative
      destruction in the Oc-C1 segment after isolated C1-2 fusion for RA. METHODS: In a
      series of 113 consecutive patients with RA-related destruction restricted to the
      craniocervical junction, 14 individuals underwent Oc-C2 fusion and 99 underwent
      surgery exclusively at the C1-2 level. After a mean follow-up period of 9.4 years
      (range 4.9-14.7 years), 46 patients were available for clinical and radiographic
      examination, including CT imaging. RESULTS: None of the 46 patients needed
      additional surgery to extend the fusion to the occiput. Despite marked
      deterioration in the subaxial cervical spine, in general there were little or no
      changes in the atlantooccipital region. All but one patient presented with bony
      fusion of the fixed C1-2 level at follow-up. CONCLUSIONS: The results of this
      investigation suggest that if the Oc-C1 joint is free of osseous destructions on
      conventional radiographs and free of abnormalities on MRI scans at the time of
      surgery (for transarticular fixation and fusion of C1-2), there is a very low
      risk for relevant destruction in the following 5-14 years. Thus, no prophylactic
      oligosegmental approach, but rather a segment-sparing monosegmental approach, is
      preferred, even in patients with high inflammatory levels.

PMID- 23157278
TI  - Multilevel anterior cervical discectomy and fusion with and without rhBMP-2: a
      comparison of dysphagia rates and outcomes in 150 patients.
AB  - OBJECT: Reported complications of recombinant human bone morphogenetic protein-2
      (rhBMP-2) use in anterior cervical discectomy and fusion (ACDF) cases include
      dysphagia and cervical swelling. However, dysphagia often occurs after multilevel
      ACDF procedures performed with allograft (without BMP) as well. To date, there
      has been no large study comparing the dysphagia rates of patients who have
      undergone multilevel ACDF using allograft spacers with those who underwent ACDF
      using polyetheretherketone (PEEK) cages filled with rhBMP2. The authors report
      one of the first such comparisons between these 2 patient cohorts. METHODS: The
      authors retrospectively reviewed 150 patient records. Group 1 (BMP group)
      consisted of 100 patients who underwent multilevel ACDF with PEEK cages filled
      with rhBMP-2 and instrumented with a cervical plate. Group 2 (allograft group)
      included a matched control cohort of 50 patients who underwent multilevel ACDF
      with allograft spacers and anterior plate fixation (without rhBMP-2). Patient
      demographics were not significantly different between the groups. Fusion was
      assessed by means of dynamic radiographs and/or CT at routine intervals.
      Complications, dysphagia incidence, standardized dysphagia score, Nurick grades,
      and fusion rates were assessed. RESULTS: The mean follow-up for the BMP group
      (Group 1) was 35 months while the mean follow-up for the allograft group (Group
      2) was 25 months. There was a complication rate of 13% in the BMP group compared
      with 8% in the allograft group (p < 0.005). There was no significant difference
      in overall dysphagia incidence between the BMP group and the allograft group (40%
      vs 44%, respectively; p > 0.05). However, there was a significant difference in
      the severity of dysphagia (using the SWAL-QOL dysphagia scoring system) between
      the 2 groups: 0.757 for the BMP group versus 0.596 for the allograft group (p <
      0.005). In subgroup analysis, the use of rhBMP-2 significantly increased the
      severity of dysphagia in patients undergoing 2-level ACDF (p < 0.005). However,
      the severity of dysphagia did not differ significantly between groups when 3- or
      4-level ACDF cases were compared. There was no pseudarthrosis in Group 1 (the BMP
      group) compared with a 16% pseudarthrosis rate in Group 2 (the allograft group)
      (p < 0.05). There was a weak correlation between the total rhBMP-2 dose and the
      dysphagia score (Kendall tau rank correlation coefficient 0.166, p = 0.046).
      CONCLUSIONS: The use of rhBMP-2 in patients undergoing 2-level ACDF significantly
      increases the severity of dysphagia (dysphagia score) without affecting the
      overall incidence of dysphagia. However, there is no statistically significant
      difference in the incidence or severity of dysphagia between patients undergoing
      3-level or 4-level ACDF treated with PEEK/rhBMP-2 and those treated with only
      allograft. The use of rhBMP-2 appears to reduce the risk of pseudarthrosis. This
      benefit is most pronounced in patients who undergo 4-level ACDF and are smokers.

PMID- 23157279
TI  - Synthesis and crystal structure of cubic Ca16Si17N34.
AB  - Since the late 1960s, the exact structure of cubic calcium silicon nitride has
      been a source of debate. This paper offers evidence that the cubic phase CaSiN(2)
      described in the literature is actually Ca(16)Si(17)N(34). Presented here is a
      method for synthesizing single crystals of cubic-calcium silicon nitride from
      calcium nitride and elemental silicon under flowing nitrogen at 1500  degrees C.
      The colorless millimeter-sized crystals of Ca(16)Si(17)N(34) with a refractive
      index (n(25)) = 1.590 were found to be cubic (a = 14.8882 A) and belong to the
      space group F43m (216). The synthesis of bulk, powdered cubic-Ca(16)Si(17)N(34)
      from calcium cyanamide and silicon is also discussed. Ca(16)Si(17)N(34) is a
      relatively air-stable refractory ceramic. In contrast to the orthorhombic phase
      of CaSiN(2), in which Ca(2+) sits in octahedral sites, this cubic phase has
      Ca(2+) in cubic sites that makes it an interesting host for new phosphors and
      gives rise to unique crystal field splitting.

PMID- 23157280
TI  - Severe cutaneous bacillus Calmette-Guerin infection in immunocompromised
      children: the relevance of skin biopsy.
AB  - Disseminated bacillus Calmette-Guerin infection (BCGitis) is an uncommon
      condition which is usually associated with primary immunodeficiency. Skin
      histopathology findings have been described in rare cases only. A retrospective
      clinicopathological study was performed to assess the potential utility of skin
      biopsies in the diagnosis, prognosis and follow-up of these patients. Four cases
      of disseminated BCGitis in children with Severe Combined ImmunoDeficiency were
      biopsied before and after Haematopoietic Stem Cell Transplantation (HSCT). The
      results were compared to the clinical and immunological status of the children.
      Early skin biopsies revealed either dense dermal infiltration by foamy
      macrophages filled with acid fast bacilli (AFB) or mycobacterial spindle-cell
      pseudotumors rich in AFB. There were no granulomas. These patterns led to the
      diagnosis of disseminated BCGitis potentially caused by severe immunodeficiency.
      After HSCT, repeated skin biopsies were performed on persistent or new cutaneous
      lesions to rule out immune reconstitution inflammatory syndrome and to check for
      tuberculoid granulomas. One patient died of BCGitis combined with graft versus
      host disease. The 3 others presented with progressive-onset well differentiated
      granulomas over a long period and recovered. Skin biopsy is a useful part of the
      diagnostic workup for disseminated BCGitis, directing the clinician toward severe
      immunodeficiency. Moreover, skin biopsy may be a useful means of monitoring
      immune restoration for prognostic purposes.

PMID- 23157281
TI  - Species-specific primers designed from RAPD products for Bithynia funiculata, the
      first intermediate host of liver fluke, Opisthorchis viverrini, in North
      Thailand.
AB  - Bithynia funiculata is the first intermediate host of the human liver fluke
      Opisthorchis viverrini in northern Thailand but its identification through
      morphological analysis is often problematic due to the shortage of gastropod
      taxonomists. As a consequence, we focused on the development of species-specific
      primers for use as an identification tool. Our work involved recovery of a 502
      base pair (bp) amplicon of unknown function through species-specific primers
      whose effectiveness was tested by analyzing specimens of B. funiculata from 3
      locations in northern Thailand. This primer set did not amplify other species in
      the Bithyniidae or in other gastropod families. By providing a tool to confirm
      morphological identifications of B. funiculata, and by enabling the
      identification of juvenile specimens and those with damaged shells, these primers
      will improve estimates of the prevalence of parasitic infections in this snail.

PMID- 23157282
TI  - Phyllocladane diterpenes from Anisomeles heyneana.
AB  - New phyllocladane diterpene, phyllocladan-16alpha,17-dihydroxy-19-oic acid (1),
      together with known phyllocladane diterpene, phyllocladan-16alpha,19-diol (2),
      cembrane diterpene ovatodiolide (3), sitosteryl-3-O-beta-D-glucoside (4), and
      verbascoside (5), were isolated from aerial parts of Anisomeles heyneana. The
      structure of compound 1 was elucidated by 1D and 2D NMR analyses which included
      HSQC, HMBC, and nuclear overhauser effect spectroscopy (NOESY) experiments as
      well as X-ray crystallography. This is the first report of phyllocladane
      diterpenes from genus Anisomeles. Compounds 1, 3, 4, and 5 were evaluated for
      inhibition of Mycobacterium tuberculosis and 3 was found to exhibit anti
      mycobacterial activity with IC90 6.53 MUg/ml. Compounds 1, 3, and 5, at 100
      MUg/ml, were also evaluated for inhibition of Thp-1 cell lines, and compounds 1
      and 3 showed 59.02% and 96.4% inhibitions, respectively.

PMID- 23157284
TI  - Alteration of the carbohydrate-binding specificity of a C-type lectin CEL-I
      mutant with an EPN carbohydrate-binding motif.
AB  - CEL-I is a Gal/GalNAc-specific C-type lectin isolated from the sea cucumber
      Cucumaria echinata. This lectin is composed of two carbohydrate-recognition
      domains (CRDs) with the carbohydrate-recognition motif QPD (Gln-Pro- Asp), which
      is generally known to exist in galactose-specific C-type CRDs. In the present
      study, a mutant CEL-I with EPN (Glu-Pro-Asn) motif, which is thought to be
      responsible for the carbohydrate-recognition of mannose-specific Ctype CRDs, was
      produced in Escherichia coli, and its effects on the carbohydrate-binding
      specificity were examined using polyamidoamine dendrimer (PD) conjugated with
      carbohydrates. Although wild-type CEL-I effectively formed complexes with N
      acetylgalactosamine (GalNAc)-PD but not with mannose-PD, the mutant CEL-I showed
      relatively weak but definite affinity for mannose-PD. These results indicated
      that the QPD and EPN motifs play a significant role in the carbohydrate
      recognition mechanism of CEL-I, especially in the discrimination of galactose and
      mannose. Additional mutations in the recombinant CEL-I binding site may further
      increase its specificity for mannose, and should provide insights into designing
      novel carbohydrate-recognition proteins.

PMID- 23157285
TI  - L-arginine as an adjuvant drug in the treatment of sickle cell anaemia.

PMID- 23157283
TI  - Specificity in S-nitrosylation: a short-range mechanism for NO signaling?
AB  - SIGNIFICANCE: Nitric oxide (NO) classical and less classical signaling mechanisms
      (through interaction with soluble guanylate cyclase and cytochrome c oxidase,
      respectively) operate through direct binding of NO to protein metal centers, and
      rely on diffusibility of the NO molecule. S-Nitrosylation, a covalent post
      translational modification of protein cysteines, has emerged as a paradigm of
      nonclassical NO signaling. RECENT ADVANCES: Several nonenzymatic mechanisms for S
      nitrosylation formation and destruction have been described. Enzymatic mechanisms
      for transnitrosylation and denitrosylation have been also studied as regulators
      of the modification of specific subsets of proteins. The advancement of
      modification-specific proteomic methodologies has allowed progress in the study
      of diverse S-nitrosoproteomes, raising clues and questions about the parameters
      for determining the protein specificity of the modification. CRITICAL ISSUES: We
      propose that S-nitrosylation is mainly a short-range mechanism of NO signaling,
      exerted in a relatively limited range of action around the NO sources, and
      tightly related to the very controlled regulation of subcellular localization of
      nitric oxide synthases. We review the nonenzymatic and enzymatic mechanisms that
      support this concept, as well as physiological examples of mammalian systems that
      illustrate well the precise compartmentalization of S-nitrosylation. FUTURE
      DIRECTIONS: Individual and proteomic studies of protein S-nitrosylation-based
      signaling should take into account the subcellular localization in order to gain
      further insight into the functional role of this modification in
      (patho)physiological settings.

PMID- 23157287
TI  - Physical tuning of cellulose-polymer interactions utilizing cationic block
      copolymers based on PCL and quaternized PDMAEMA.
AB  - In this work, the objective was to synthesize and evaluate the properties of a
      compatibilizer based on poly(epsilon-caprolactone) aimed at tuning the surface
      properties of cellulose fibers used in fiber-reinforced biocomposites. The
      compatibilizer is an amphiphilic block copolymer consisting of two different
      blocks which have different functions. One block is cationic, quaternized poly(2
      (dimethylamino)ethyl methacrylate) (PDMAEMA) and can therefore electrostatically
      attach to anionic reinforcing materials such as cellulose-based fibers/fibrils
      under mild conditions in water. The other block consists of poly(epsilon
      caprolactone) (PCL) which can decrease the surface energy of a cellulose surface
      and also has the ability to form physical entanglements with a PCL surface
      thereby improving the interfacial adhesion. Atom Transfer Radical Polymerization
      (ATRP) and Ring-Opening Polymerization (ROP) were used to synthesize three block
      copolymers with the same length of the cationic PDMAEMA block but with different
      lengths of the PCL blocks. The block copolymers form cationic micelles in water
      which can adsorb to anionic surfaces such as silicon oxide and cellulose-model
      surfaces. After heat treatment, the contact angles of water on the treated
      surfaces increased significantly, and contact angles close to those of pure PCL
      were obtained for the block copolymers with longer PCL blocks. AFM force
      measurements showed a clear entangling behavior between the block copolymers and
      a PCL surface at about 60  degrees C, which is important for the formation of an
      adhesive interface in the final biocomposites. This demonstrates that this type
      of amphiphilic block copolymer can be used to improve interactions in
      biocomposites between anionic reinforcing materials such as cellulose-based
      fibers/fibrils and less polar matrices such as PCL.

PMID- 23157286
TI  - High-resolution in vivo imaging of regenerating dendrites of Drosophila sensory
      neurons during metamorphosis: local filopodial degeneration and heterotypic
      dendrite-dendrite contacts.
AB  - Neuronal circuits that are formed in early development are reorganized at later
      developmental stages to support a wide range of adult behaviors. At Drosophila
      pupal stages, one example of this reorganization is dendritic remodeling of
      multidendritic neurons, which is accomplished by pruning and subsequent
      regeneration of branches in environments quite distinct from those in larval
      life. Here, we used long-term in vivo time-lapse recordings at high
      spatiotemporal resolution and analyzed the dynamics of two adjacent cell types
      that remodel dendritic arbors, which eventually innervate the lateral plate of
      the adult abdomen. These neurons initially exhibited dynamic extension,
      withdrawal and local degeneration of filopodia that sprouted from all along the
      length of regenerating branches. At a midpupal stage, branches extending from the
      two cell types started fasciculating with each other, which prompted us to test
      the hypothesis that this heterotypic contact may serve as a guiding scaffold for
      shaping dendritic arbors. Unexpectedly, our cell ablation study gave only
      marginal effects on the branch length and the arbor shape. This result suggests
      that the arbor morphology of the adult neurons in this study can be specified
      mostly in the absence of the dendrite-dendrite contact.

PMID- 23157288
TI  - Copy Number Variation detection from 1000 Genomes Project exon capture sequencing
      data.
AB  - BACKGROUND: DNA capture technologies combined with high-throughput sequencing now
      enable cost-effective, deep-coverage, targeted sequencing of complete exomes.
      This is well suited for SNP discovery and genotyping. However there has been
      little attention devoted to Copy Number Variation (CNV) detection from exome
      capture datasets despite the potentially high impact of CNVs in exonic regions on
      protein function. RESULTS: As members of the 1000 Genomes Project analysis
      effort, we investigated 697 samples in which 931 genes were targeted and sampled
      with 454 or Illumina paired-end sequencing. We developed a rigorous Bayesian
      method to detect CNVs in the genes, based on read depth within target regions.
      Despite substantial variability in read coverage across samples and targeted
      exons, we were able to identify 107 heterozygous deletions in the dataset. The
      experimentally determined false discovery rate (FDR) of the cleanest dataset from
      the Wellcome Trust Sanger Institute is 12.5%. We were able to substantially
      improve the FDR in a subset of gene deletion candidates that were adjacent to
      another gene deletion call (17 calls). The estimated sensitivity of our call-set
      was 45%. CONCLUSIONS: This study demonstrates that exonic sequencing datasets,
      collected both in population based and medical sequencing projects, will be a
      useful substrate for detecting genic CNV events, particularly deletions. Based on
      the number of events we found and the sensitivity of the methods in the present
      dataset, we estimate on average 16 genic heterozygous deletions per individual
      genome. Our power analysis informs ongoing and future projects about sequencing
      depth and uniformity of read coverage required for efficient detection.

PMID- 23157289
TI  - Reflections on biocatalysis involving phosphorus.
AB  - Early studies on chemical synthesis of biological molecules can be seen to
      progress to preparation and biological evaluation of phosphonates as analogues of
      biological phosphates, with emphasis on their isosteric and isopolar character.
      Work with such mimics progressed into structural studies with a range of
      nucleotide-utilising enzymes. The arrival of metal fluorides as analogues of the
      phosphoryl group, PO(3)(-), for transition state (TS) analysis of enzyme
      reactions stimulated the symbiotic deployment of (19)F NMR and protein
      crystallography. Characteristics of enzyme transition state analogues are
      reviewed for a range of reactions. From the available MF(x) species,
      trifluoroberyllate gives tetrahedral mimics of ground states (GS) in which
      phosphate is linked to carboxylate and phosphate oxyanions. Tetrafluoroaluminate
      is widely employed as a TS mimic, but it necessarily imposes octahedral geometry
      on the assembled complexes, whereas phosphoryl transfer involves trigonal
      bipyramidal (tbp) geometry. Trifluoromagnesate (MgF(3)(-)) provides the near
      ideal solution, delivering tbp geometry and correct anionic charge. Some of the
      forty reported tbp structures assigned as having AlF(3)(0) cores have been
      redefined as trifluoromagnesate complexes. Transition state analogues for a range
      of kinases, mutases, and phosphatases provide a detailed description of mechanism
      for phosphoryl group transfer, supporting the concept of charge balance in their
      TS and of concerted-associative pathways for biocatalysis. Above all,
      superposition of GS and TS structures reveals that in associative phosphoryl
      transfer, the phosphorus atom migrates through a triangle of three, near
      stationary, equatorial oxygens. The extension of these studies to near attack
      conformers further illuminates enzyme catalysis of phosphoryl transfer.

PMID- 23157290
TI  - Recharging oxidative protein repair: catalysis by methionine sulfoxide reductases
      towards their amino acid, protein, and model substrates.
AB  - The sulfur-containing amino acid methionine (Met) in its free and amino acid
      residue forms can be readily oxidized to the R and S diastereomers of methionine
      sulfoxide (MetO). Methionine sulfoxide reductases A (MSRA) and B (MSRB) reduce
      MetO back to Met in a stereospecific manner, acting on the S and R forms,
      respectively. A third MSR type, fRMSR, reduces the R form of free MetO. MSRA and
      MSRB are spread across the three domains of life, whereas fRMSR is restricted to
      bacteria and unicellular eukaryotes. These enzymes protect against abiotic and
      biotic stresses and regulate lifespan. MSRs are thiol oxidoreductases containing
      catalytic redox-active cysteine or selenocysteine residues, which become oxidized
      by the substrate, requiring regeneration for the next catalytic cycle. These
      enzymes can be classified according to the number of redox-active cysteines
      (selenocysteines) and the strategies to regenerate their active forms by
      thioredoxin and glutaredoxin systems. For each MSR type, we review catalytic
      parameters for the reduction of free MetO, low molecular weight MetO-containing
      compounds, and oxidized proteins. Analysis of these data reinforces the concept
      that MSRAs reduce various types of MetO-containing substrates with similar
      efficiency, whereas MSRBs are specialized for the reduction of MetO in proteins.

PMID- 23157291
TI  - Catalytic mechanism and substrate specificity of HIF prolyl hydroxylases.
AB  - This review describes the catalytic mechanism, substrate specificity, and
      structural peculiarities of alpha-ketoglutarate dependent nonheme iron
      dioxygenases catalyzing prolyl hydroxylation of hypoxia-inducible factor (HIF).
      Distinct localization and regulation of three isoforms of HIF prolyl hydroxylases
      suggest their different roles in cells. The recent identification of novel
      substrates other than HIF, namely beta2-adrenergic receptor and the large subunit
      of RNA polymerase II, places these enzymes in the focus of drug development
      efforts aimed at development of isoform-specific inhibitors. The challenges and
      prospects of designing isoform-specific inhibitors are discussed.

PMID- 23157292
TI  - Telomerase RNA biosynthesis and processing.
AB  - Telomerase synthesizes repetitive G-rich sequences (telomeric repeats) at the
      ends of eukaryotic chromosomes. This mechanism maintains the integrity of the
      genome, as telomere shortening leads to degradation and fusion of chromosomes.
      The core components of telomerase are the telomerase catalytic subunit and
      telomerase RNA, which possesses a small template region serving for the synthesis
      of a telomeric repeat. Mutations in the telomerase RNA are associated with some
      cases of aplastic anemia and also cause dyskeratosis congenita, myelodysplasia,
      and pulmonary fibrosis. Telomerase is active in 85% of cancers, and telomerase
      activation is one of the first steps in cell transformation. The study of
      telomerase and pathways where this enzyme is involved will help to understand the
      mechanism of the mentioned diseases and to develop new approaches for their
      treatment. In this review we describe the modern conception of telomerase RNA
      biosynthesis, processing, and functioning in the three most studied systems -
      yeast, vertebrates, and ciliates.

PMID- 23157293
TI  - Octaheme nitrite reductases: structure and properties.
AB  - Octaheme oxidoreductases are widespread among various bacterial taxa involved in
      the biogeochemical nitrogen cycle. The evolution of octaheme oxidoreductases of
      the nitrogen cycle from the evolutionarily more ancient pentaheme nitrite
      reductases was accompanied by changes in function from reduction of nitrogen
      oxides to their oxidation under changing environmental conditions. Octaheme
      nitrite reductases, which are the subject of the present review, are of a
      transitional form that combines structural and functional characteristics of
      pentaheme reductases and octaheme oxidases and possesses a number of unique
      features typical of only this family of enzymes. The review summarizes data on
      structure-function investigations of the family of octaheme nitrite reductases.
      Emphasis is given to comparison of the structures and functions of octaheme
      nitrite reductases and other multiheme oxidoreductases of the nitrogen cycle.

PMID- 23157294
TI  - Creation of catalytic antibodies metabolizing organophosphate compounds.
AB  - Development of new ways of creating catalytic antibodies possessing defined
      substrate specificity towards artificial substrates has important fundamental and
      practical aspects. Low immunogenicity combined with high stability of
      immunoglobulins in the blood stream makes abzymes potent remedies. A good example
      is the cocaine-hydrolyzing antibody that has successfully passed clinical trials.
      Creation of an effective antidote against organophosphate compounds, which are
      very toxic substances, is a very realistic goal. The most promising antidotes are
      based on cholinesterases. These antidotes are now expensive, and their production
      methods are inefficient. Recombinant antibodies are widely applied in clinics and
      have some advantage compared to enzymatic drugs. A new potential abzyme antidote
      will combine effective catalysis comparable to enzymes with high stability and
      the ability to switch on effector mechanisms specific for antibodies. Examples of
      abzymes metabolizing organophosphate substrates are discussed in this review.

PMID- 23157295
TI  - Time-dependent kinetic complexities in cholinesterase-catalyzed reactions.
AB  - Cholinesterases (ChEs) display a hysteretic behavior with certain substrates and
      inhibitors. Kinetic cooperativity in hysteresis of ChE-catalyzed reactions is
      characterized by a lag or burst phase in the approach to steady state. With some
      substrates damped oscillations are shown to superimpose on hysteretic lags. These
      time dependent peculiarities are observed for both butyrylcholinesterase and
      acetylcholinesterase from different sources. Hysteresis in ChE-catalyzed
      reactions can be interpreted in terms of slow transitions between two enzyme
      conformers E and E'. Substrate can bind to E and/or E', both Michaelian complexes
      ES and Epsilon'S can be catalytically competent, or only one of them can make
      products. The formal reaction pathway depends on both the chemical structure of
      the substrate and the type of enzyme. In particular, damped oscillations develop
      when substrate exists in different, slowly interconvertible, conformational,
      and/or micellar forms, of which only the minor form is capable of binding and
      reacting with the enzyme. Biphasic pseudo-first-order progressive inhibition of
      ChEs by certain carbamates and organophosphates also fits with a slow equilibrium
      between two reactive enzyme forms. Hysteresis can be modulated by medium
      parameters (pH, chaotropic and kosmotropic salts, organic solvents, temperature,
      osmotic pressure, and hydrostatic pressure). These studies showed that water
      structure plays a role in hysteretic behavior of ChEs. Attempts to provide a
      molecular mechanism for ChE hysteresis from mutagenesis studies or
      crystallographic studies failed so far. In fact, several lines of evidence
      suggest that hysteresis is controlled by the conformation of His438, a key
      residue in the catalytic triad of cholinesterases. Induction time may depend on
      the probability of His438 to adopt the operative conformation in the catalytic
      triad. The functional significance of ChE hysteresis is puzzling. However, the
      accepted view that proteins are in equilibrium between preexisting functional and
      non-functional conformers, and that binding of a ligand to the functional form
      shifts equilibrium towards the functional conformation, suggests that slow
      equilibrium between two conformational states of these enzymes may have a
      regulatory function in damping out the response to certain ligands and
      irreversible inhibitors. This is particularly true for immobilized (membrane
      bound) enzymes where the local substrate and/or inhibitor concentrations depend
      on influx in crowded organellar systems, e.g. cholinergic synaptic clefts.
      Therefore, physiological or toxicological relevance of the hysteretic behavior
      and damped oscillations in ChE-catalyzed reactions and inhibition cannot be ruled
      out.

PMID- 23157296
TI  - Kinetic mechanism of the interaction of Saccharomyces cerevisiae AP-endonuclease
      1 with DNA substrates.
AB  - The apurinic/apyrimidinic endonuclease from Saccharomyces cerevisiae Apn1 is one
      of the key enzymes involved in base excision repair of DNA lesions. A major
      function of the enzyme is to cleave the upstream phosphodiester bond of an
      apurinic/apyrimidinic site (AP-site), leading to the formation of a single-strand
      break with 3'-hydroxyl (OH) and 5'-deoxyribose phosphate (dRP) termini. In this
      study, the pre-steady-state kinetics and conformational dynamics of DNA
      substrates during their interaction with Apn1 were investigated. A stopped-flow
      method with detection of the fluorescence intensity of 2-aminopurine and
      pyrrolocytosine located adjacent or opposite to the damage was used. It was found
      that upon interaction with Apn1, both DNA strands undergo a number of rapid
      changes. The location of fluorescent analogs of heterocyclic bases in DNA does
      not influence the catalytic step of the reaction. Comparison of data obtained for
      yeast Apn1 and reported data (Kanazhevskaya, L. Yu., Koval, V. V., Vorobjev, Yu.
      N., and Fedorova, O. S. (2012) Biochemistry, 51, 1306-1321) for human Ape1
      revealed some differences in their interaction with DNA substrates.

PMID- 23157298
TI  - Engineering of substrate specificity of D-amino acid oxidase from the yeast
      Trigonopsis variabilis: directed mutagenesis of Phe258 residue.
AB  - Natural D-amino acid oxidases (DAAO) are not suitable for selective determination
      of D-amino acids due to their broad substrate specificity profiles. Analysis of
      the 3D-structure of the DAAO enzyme from the yeast Trigonopsis variabilis
      (TvDAAO) revealed the Phe258 residue located at the surface of the protein
      globule to be in the entrance to the active site. The Phe258 residue was mutated
      to Ala, Ser, and Tyr residues. The mutant TvDAAOs with amino acid substitutions
      Phe258Ala, Phe258Ser, and Phe258Tyr were purified to homogeneity and their
      thermal stability and substrate specificity were studied. These substitutions
      resulted in either slight stabilization (Phe258Tyr) or destabilization
      (Phe258Ser) of the enzyme. The change in half-inactivation periods was less than
      twofold. However, these substitutions caused dramatic changes in substrate
      specificity. Increasing the side chain size with the Phe258Tyr substitution
      decreased the kinetic parameters with all the D-amino acids studied. For the two
      other substitutions, the substrate specificity profiles narrowed. The catalytic
      efficiency increased only for D-Tyr, D-Phe, and D-Leu, and for all other D-amino
      acids this parameter dramatically decreased. The improvement of catalytic
      efficiency with D-Tyr, D-Phe, and D-Leu for TvDAAO Phe258Ala was 3.66-, 11.7-,
      and 1.5-fold, and for TvDAAO Phe258Ser it was 1.7-, 4.75-, and 6.61-fold,
      respectively.

PMID- 23157297
TI  - Biogenic polyamines spermine and spermidine activate RNA polymerase and inhibit
      RNA helicase of hepatitis C virus.
AB  - Influence of the biogenic polyamines spermine, spermidine, and putrescine as well
      as their derivatives on the replication enzymes of hepatitis C virus (HCV) was
      investigated. It was found that spermine and spermidine activate HCV RNA
      dependent RNA polymerase (NS5B protein). This effect was not caused by the
      stabilization of the enzyme or by competition with template-primer complex, but
      rather it was due to achievement of true maximum velocity V(max). Natural
      polyamines and their derivatives effectively inhibited the helicase reaction
      catalyzed by another enzyme of HCV replication - helicase/NTPase (NS3 protein).
      However, these compounds affected neither the NTPase reaction nor its activation
      by polynucleotides. Activation of the HCV RNA polymerase and inhibition of the
      viral helicase were shown at physiological concentrations of the polyamines.
      These data suggest that biogenic polyamines may cause differently directed
      effects on the replication of the HCV genome in an infected cell.

PMID- 23157299
TI  - Purification, biochemical characterization, and structure of recombinant endo-1,4
      beta-xylanase XylE.
AB  - The gene xylE encoding endo-1,4-beta-xylanase from the 10th family of glycosyl
      hydrolases produced by the mycelial fungus Penicillium canescens has been
      expressed under the control of the strong promoter of the bgaS gene encoding beta
      galactosidase from P. canescens. As a result, a strain-producer of endoxylanase
      XylE was developed. The recombinant enzyme was isolated and purified to
      homogeneity with specific activity of 50 U/mg. The physicochemical and
      biochemical properties of the endoxylanase were studied. The maximal enzymatic
      activity was observed at pH 6.0 and 70 degrees C. Endoxylanase XylE was shown to
      be a highly thermostable enzyme with half-inactivation period tau(1/2) of 7 h at
      60 degrees C. The kinetic parameters were 0.52 mg/ml (K(m)) and 75 umol/min per
      mg (V(max)) using birch xylan as the substrate. Crystals of endoxylonase XylE
      were obtained, and the 3D structure was solved at 1.47 A resolution. The 3D
      structure of an endo-1,4-beta-xylanase from the 10th family containing
      carbohydrate and unique cyclic structure located at the C-terminus of the
      polypeptide chain was obtained for the first time.

PMID- 23157300
TI  - Stabilization of plant formate dehydrogenase by rational design.
AB  - Recombinant formate dehydrogenase (FDH, EC 1.2.1.2) from soy Glycine max (SoyFDH)
      has the lowest values of Michaelis constants for formate and NAD+ among all
      studied formate dehydrogenases from different sources. Nevertheless, it also has
      the lower thermal stability compared to enzymes from bacteria and yeasts. The
      alignment of full sequences of FDHs from different sources as well as structure
      of apo- and holo-forms of SoyFDH has been analyzed. Ten mutant forms of SoyFDH
      were obtained by site-directed mutagenesis. All of them were purified to
      homogeneity and their thermal stability and substrate specificity were studied.
      Thermal stability was investigated by studying the inactivation kinetics at
      different temperatures and by differential scanning calorimetry (DSC). As a
      result, single-point (Ala267Met) and double mutants (Ala267Met/Ile272Val) were
      found to be more stable than the wild-type enzyme at high temperatures. The
      stabilization effect depends on temperature, and at 52 degrees C it was 3.6- and
      11-fold, respectively. These mutants also showed higher melting temperatures in
      DSC experiments - the differences in maxima of the melting curves (T(m)) for the
      single and double mutants were 2.7 and 4.6 degrees C, respectively. For mutations
      Leu24Asp and Val127Arg, the thermal stability at 52 degrees C decreased 5- and
      2.5-fold, respectively, and the T(m) decreased by 3.5 and 1.7 degrees C,
      respectively. There were no differences in thermal stability of six mutant forms
      of SoyFDH - Gly18Ala, Lys23Thr, Lys109Pro, Asn247Glu, Val281Ile, and Ser354Pro.
      Analysis of kinetic data showed that for the enzymes with mutations Val127Arg and
      Ala267Met the catalytic efficiency increased 1.7- and 2.3-fold, respectively.

PMID- 23157301
TI  - Expression of human interferon-alpha8 synthetic gene under P(BAD) promoter.
AB  - Recombinant human interferon-alpha8 (rhIFN-alpha8) was obtained by synthesizing a
      codon-optimized gene in a two-step polymerase chain reaction (PCR) and expressing
      it in Escherichia coli. The gene encoding human IFN-alpha8 shows a high content
      of rare codons. These were replaced based on E. coli codon usage and balancing TA
      GC ratio contents of the entire gene. The two-step PCR was performed using long
      (45-60 nucleotides) overlapped primers and two Taq polymerases (pfu clone and GC
      rich system) and resulted in a DNA band of 504 base pairs (bp) corresponding to
      the calculated size of the IFN-alpha8 coding sequence; the pfu clone failed to
      amplify the gene in the correct size without unspecific bands. The full gene was
      cloned into the pBAD-TOPO expression vector. After cloning, the gene was
      reoriented by NcoI restriction digestion and religation. The ligated pBAD-TOPO
      IFN-alpha8 (pBAD-IFNalpha8) plasmid carried the IFN-alpha8 gene under
      transcriptional control of the L-arabinose-inducible P(BAD) promoter. IFN-alpha8
      expression was optimized with respect to L-arabinose concentration, temperature,
      and time of induction in shake flask cultures to maximize the yield of soluble
      IFN-alpha8. The produced IFN-alpha8 was characterized by polyacrylamide gel
      electrophoresis and immunoassays. After purification on DEAE-Sepharose, the yield
      was 100 mg/liter. The antiviral and anticancer activities of the IFN-alpha8 were
      evaluated in comparison with IFN-alpha2a, and the results are discussed.

PMID- 23157302
TI  - Multilevel conductance switching of memory device through photoelectric effect.
AB  - A photoelectronic switch of a multilevel memory device has been achieved using a
      meta-conjugated donor-bridge-acceptor (DBA) molecule. Such a DBA optoelectronic
      molecule responds to both the optical and electrical stimuli. The device exhibits
      good electrical bistable switching behaviors under dark, with a large ON/OFF
      ratio more than 10(6). In cooperation with the UV light, photoelectronic ternary
      states are addressable in a bistable switching system. On the basis of the CV
      measurement, charge carriers transport modeling, quantum chemical calculation,
      and absorption spectra analysis, the mechanism of the DBA memory is suggested to
      be attributed to the substep charge transfer transition process. The capability
      of tailoring photoelectrical properties is a very promising strategy to explore
      the multilevel storage, and it will give a new opportunity for designing
      multifunctional devices.

PMID- 23157303
TI  - (1)H and (13)C magic-angle spinning nuclear magnetic resonance studies of the
      chicken eggshell.
AB  - The chicken eggshell, a product of biomineralization, contains inorganic and
      organic substances whose content changes during the incubation process. Bloch
      decay (BD) (1)H, (13)C, and cross-polarization (CP) (13)C nuclear magnetic
      resonance (NMR) spectra of chicken eggshells were acquired under magic-angle
      spinning (MAS). Variable contact time (13)C CP MAS NMR experiments revealed the
      signals of carbonyl groups from organic and inorganic compounds. In the (13)C BD
      NMR spectra, a single peak at 168.1 ppm was detected, whereas in the (1)H BD
      spectra, the signals from water and the bicarbonate ion were assigned. A
      simultaneous decrease of the water signal in the (1)H MAS NMR spectra and an
      increase of the carbonate ion signal in the (13)C CP MAS NMR spectra of eggshells
      collected during the incubation period indicate the substitution of calcium ions
      by hydrogen ions in the calcium carbonate crystalline phase during the incubation
      of an egg.

PMID- 23157304
TI  - Supplemental hydrogen sulphide protects transplant kidney function and prolongs
      recipient survival after prolonged cold ischaemia-reperfusion injury by
      mitigating renal graft apoptosis and inflammation.
AB  - What's known on the subject? and What does the study add? Hydrogen sulphide (H(2)
      S) has recently been classified as a member of the family of small gaseous
      molecules called gasotransmitters and has been found to have many important
      physiological functions. Several recent studies have elucidated the protective
      effects of H(2) S in many models of tissue ischaemia-reperfusion injury (IRI),
      including hepatic, myocardial, pulmonary, cerebral and renal IRI. It has
      previously been shown that H(2) S has a number of properties that may contribute
      to its protection against IRI, including vasodilatory, anti-apoptotic, anti
      inflammatory and anti-oxidant effects, although the specific actions appear to
      vary between tissues. The few studies investigating the effects of H(2) S against
      renal IRI have only involved clamping of the renal pedicle to induce warm IRI.
      This study investigated the protective effects of H(2) S in the context of renal
      transplantation (RTx), which generally involves a more severe period of prolonged
      cold IRI. A previous study investigated the actions of H(2) S in RTx, but it was
      performed ex vivo and did not involve actual transplantation of donor kidneys. To
      our knowledge, this is the first study using a clinically relevant model of RTx
      to show that treatment of donor kidneys with H(2) S during preservation is
      protective against prolonged cold IRI. These findings suggest that H(2) S has
      potential utility in improving clinical organ preservation techniques and
      increasing the overall success of organ transplantation. OBJECTIVE: * To
      characterize the effects of hydrogen sulphide (H(2) S), an endogenously produced
      molecule recently described to have protective effects against warm ischaemic
      tissue injury, in mitigating transplantation-associated prolonged cold ischaemia
      reperfusion injury (IRI) in a clinically applicable in vivo model of renal
      transplantation (RTx). MATERIALS AND METHODS: * After undergoing bilateral native
      nephrectomy, Lewis rats underwent RTx with kidneys that were flushed with either
      cold (4  degrees C) standard University of Wisconsin preservation solution (UW)
      or cold UW + 150 uM NaHS (H(2) S) solution and stored for 24 h at 4  degrees C in
      the same solution. * Recipient rats were monitored for a 14-day time course using
      metabolic cages to assess various characteristics of renal graft function. *
      Renal grafts were removed at time of death or after the rats were killed for
      histological, immunohistochemical and quantitative PCR analysis. RESULTS: * H(2)
      S-treated rats exhibited immediate and significant (P < 0.05) decreases in serum
      creatinine levels, increased urine output and increased survival compared with UW
      treated rats. * H(2) S-treated grafts showed significantly reduced glomerular and
      tubular necrosis and apoptosis, diminished graft neutrophil and macrophage
      infiltrates and a trend towards improved inflammatory and anti-apoptotic cytokine
      profiles. CONCLUSION: * Our results provide the first evidence that supplemental
      H(2) S can mitigate renal graft IRI incurred during transplantation and prolonged
      cold storage, improving early graft function and recipient survival in a
      clinically applicable model of RTx.

PMID- 23157305
TI  - Is there a link between long-distance travel and ischaemic stroke?

PMID- 23157306
TI  - Pharmacokinetics of chloramphenicol following administration of intravenous and
      subcutaneous chloramphenicol sodium succinate, and subcutaneous chloramphenicol,
      to koalas (Phascolarctos cinereus).
AB  - Clinically normal koalas (n = 19) received a single dose of intravenous (i.v.)
      chloramphenicol sodium succinate (SS) (25 mg/kg; n = 6), subcutaneous (s.c.)
      chloramphenicol SS (60 mg/kg; n = 7) or s.c. chloramphenicol base (60 mg/kg; n =
      6). Serial plasma samples were collected over 24-48 h, and chloramphenicol
      concentrations were determined using a validated high-performance liquid
      chromatography assay. The median (range) apparent clearance (CL/F) and
      elimination half-life (t(1/2)) of chloramphenicol after i.v. chloramphenicol SS
      administration were 0.52 (0.35-0.99) L/h/kg and 1.13 (0.76-1.40) h, respectively.
      Although the area under the concentration-time curve was comparable for the two
      s.c. formulations, the absorption rate-limited disposition of chloramphenicol
      base resulted in a lower median C(max) (2.52; range 0.75-6.80 MUg/mL) and longer
      median tmax (8.00; range 4.00-12.00 h) than chloramphenicol SS (C(max) 20.37,
      range 13.88-25.15 MUg/mL; t(max) 1.25, range 1.00-2.00 h). When these results
      were compared with susceptibility data for human Chlamydia isolates, the expected
      efficacy of the current chloramphenicol dosing regimen used in koalas to treat
      chlamydiosis remains uncertain and at odds with clinical observations.

PMID- 23157307
TI  - The new version of a patient classification instrument: assessment of
      psychometric properties.
AB  - AIMS: This paper assessed the reliability and construct validity of the new
      version of a patient classification instrument. BACKGROUND: In the development of
      patient classification instruments, monitoring validity and reliability is
      essential to assure that patient care requirements and nursing staff workload are
      appropriately measured. DESIGN METHOD: The sample included 194 patients
      (construct validity test) and 60 patients (inter-rater reliability test) at
      medical, surgical, and specialized wards of a teaching hospital in the south east
      of Brazil. The study was conducted in 2009-2010. For analysis purposes,
      Spearman's correlation and Cronbach's alpha (internal consistency) were used, and
      weighted kappa (inter-rater reliability), factor analysis with principal axis
      factoring extraction method (construct validity) and ordinal regression
      (instrument's predictive ability). RESULTS: A high level of inter-rater agreement
      was found. The importance of all care areas and their contribution to distinguish
      patient care needs and category in the new instrument were demonstrated. Results
      also showed the instrument's high predictive ability (99.6%). CONCLUSION: The
      findings give the evidence that the new scale is a reliable and valid tool to
      assess patient care needs and care category and that it can be used to guide
      nursing management practice in determining the nursing staff workload.

PMID- 23157308
TI  - Two new compounds from Hicriopteris glauca and their potential antitumor
      activities.
AB  - Chemical examination of the EtOAc extract from the stems of Hicriopteris glauca
      (Thunb) Ching. led to the isolation of two new compounds: lunularic acid 4'
      glucoside and 2,9-dihydroxy-4,7-megastigmadiene-3-O-beta-glucoside. Their
      structures were elucidated on the basis of spectral analysis and by comparing
      their spectral data with those in literature. Two compounds, along with the
      petroleum ether, chloroform, EtOAc, and n-BuOH extracts, were tested for
      cytotoxic activities. Only the n-BuOH extract showed antitumor activity against
      human melanoma A375 cells with IC50 values of 0.80 MUg/ml.

PMID- 23157309
TI  - Sorafenib is effective for imatinib-resistant FIP1L1/PDGFRA T674I mutation
      positive acute myeloid leukemia with eosinophilia.

PMID- 23157310
TI  - Molecular dynamics simulations of retinoblastoma protein.
AB  - Tumor suppressor proteins play a crucial role in cell cycle regulation.
      Retinoblastoma protein (pRB) is one among them which regulates G1-S transition by
      binding with transcription factors. The activity of pRB is deregulated by cyclin
      dependent kinases-mediated hyper-phosphorylation and also due to cancer-derived
      mutations. In addition, it is also deactivated by binding of viral onco-proteins
      such as large T antigen, E1A, and E7. These viral proteins initially recognize
      pRB through their conserved LxCxE motif and facilitate dissociation of
      preexisting pRB-E2F complex. Based on these features, molecular dynamics (MD)
      simulation is performed for four different states of pRB for which the crystal
      structure is available. The unliganded/apo form and complex forms with E2F and E7
      peptides reveal the molecular mechanism behind the activation and inactivation of
      pRB. In addition, the ternary complex of pRB with both E7 and E2F (for which no
      crystal structure is available) is modeled and simulated to understand the
      influence of binding of one ligand on the other. The variations in the three
      major factors such as conformational changes, inter- and intra-molecular
      interactions, and binding free energies between the apo and complex forms confirm
      the possibility for designing a small molecule inhibitor to inhibit pRB-E7
      interactions without altering the prebound E2F. The present study deals with the
      molecular modeling and MD simulations of pRB in free and ligand-bound forms and
      confirms that pRB could be a valid target for the anticancer drug design when the
      cancer is induced by the viral onco-proteins and forms a clear base for designing
      E7 antagonists. 

PMID- 23157311
TI  - Letter from the editor.

PMID- 23157312
TI  - Interaction of In(I) and Tl(I) cations with 2,6-diaryl pyridine ligands: cation
      encapsulation within a very weakly interacting N/arene host environment.
AB  - The interaction of 2,6-dimesitylpyridine with Tl(I) and In(I) cations has been
      investigated with a view to developing tractable molecular M(I) compounds which
      are soluble in organic media. In stark contrast to isosteric and isoelectronic
      terphenyl systems, complexes featuring the [(2,6-Mes(2)py)M](+) fragment feature
      very weak metal-ligand interactions in the solid state, as revealed by M-N
      distances of the order of 2.45 A (M = In) and 2.64 A (M = Tl). While additional
      weak pi interactions are observed with arene solvate molecules in these systems,
      the related 2:1 complex [(2,6-Mes(2)py)(2)In][BAr(f)(4)] features an In(I) center
      wholly encapsulated by the bulky Mes(2)py donors, and even longer In-N distances
      [2.586(6) and 2.662(5) A]. These contacts are about 0.5 A greater than the sum of
      the respective covalent radii (2.13 A) and provide evidence for an effectively
      "naked" In(I) cation stabilized to a minor extent by orbital interactions.

PMID- 23157313
TI  - The question of electrophilic vs nucleophilic addition of cyclic beta-dicarbonyl
      phenyliodonium ylides: electrophilic cycloaddition of diphenylketene.
AB  - The reaction of beta-dicarbonyl phenyliodonium ylides with diphenylketene at room
      temperature affords mixtures of lactone and aurone derivatives. The initial
      electrophilic attack of the iodonium ylide on the C(beta) position of the
      diphenylketene, followed by cyclization of the zwitterionic species, and
      subsequent ejection of iodobenzene, affords the lactone and aurone cycloadducts.
      Treatment of beta-dicarbonyl iodonium ylides with acyl chlorides yields alpha
      chloroenones with good to excellent yields.

PMID- 23157314
TI  - redox Signaling by 8-nitro-cyclic guanosine monophosphate: nitric oxide- and
      reactive oxygen species-derived electrophilic messenger.
AB  - SIGNIFICANCE: Emerging evidence has revealed that nitric oxide (NO)- and reactive
      oxygen species (ROS)-derived electrophiles formed in cells mediate signal
      transduction for responses to oxidative stress. RECENT ADVANCES: The cyclic
      nucleotide with a nitrated guanine moiety-8-nitroguanosine 3',5'-cyclic
      monophosphate (8-nitro-cGMP)-first identified in 2007 as a second messenger for
      NO and ROS-has certain unique properties that its parental cGMP lacks. For
      example, it can react with particular protein Cys thiols because of its
      electrophilicity and can cause unique post-translational modifications of redox
      sensor proteins such as Keap1 and H-Ras. CRITICAL ISSUES: Site-specific S
      guanylation of Keap1 at Cys434 induced NO- and ROS-mediated adaptive responses to
      oxidative stress. H-Ras Cys184 S-guanylation was recently found to be involved in
      activation of mitogen-activated protein kinase cascades as manifested by cellular
      senescence and heart failure in mouse cardiac hypertrophy models. The latest
      finding related to the concept of electrophile-based redox signaling is a potent
      regulatory function of endogenously produced hydrogen sulfide for redox signaling
      via 8-nitro-cGMP. FUTURE DIRECTIONS: Electrophile modification of 8-nitro-cGMP,
      as a second messenger for NO and ROS, by hydrogen sulfide (i.e., electrophile
      sulfhydration) can most likely effect physiological regulation of cellular redox
      signaling. Continued investigation of the precise function of cellular hydrogen
      sulfide that may control electrophile-dependent redox cellular signaling, most
      typically via 8-nitro-cGMP formation, may provide novel insights into the
      molecular mechanisms of oxidative stress responses, oxidative stress-related
      pathology and disease control, and development of therapeutics for various
      diseases.

PMID- 23157315
TI  - Helminth infracommunity structure of Leptodactylus melanonotus (Anura) in Tres
      Palos, Guerrero, and other records for this host species in Mexico.
AB  - The amphibian genus Leptodactylus includes around 50 species, of which only 2 are
      distributed in Mexico; the helminth fauna of these 2 species is poorly known. As
      part of a research program on amphibian parasites in Mexico from 1997 to 2005,
      281 sabinal frogs Leptodactylus melanonotus from 42 localities in 11 Mexican
      states were examined from a helminthological perspective. A total of 20 taxa of
      helminths-7 digeneans (5 adults, 2 larvae) and 13 nematodes (8 adults, 5 larvae)
      was found to infect this amphibian host species. These data represent 105 new
      locality records, and 11 taxa are recorded in L. melanonotus for the first time.
      Infracommunity analyses of the sabinal frogs from Tres Palos indicated that these
      hosts are depauperate. The helminth community is dominated by specialist species,
      with Cosmocerca podicipinus the most common in almost 50% of the
      infracommunities. Percutaneous infection and predator-prey interactions were the
      2 most common infection routes by helminths in frogs from Tres Palos, with 79% of
      the parasites recruited via skin penetration. Finally, our results show that the
      helminth fauna parasitizing L. melanonotus throughout Mexico has low similarity
      with the helminth fauna of leptodactylids studied comprehensively in South
      America, with only 2 digeneans and 3 nematodes being shared by hosts from both
      regions. As a result of our survey, the number of helminth species parasitizing
      L. melanonotus increased to 34. Considering its native distribution range, this
      number is now 36 with the inclusion of the nematodes Oswaldocruzia costaricensis
      and Cruzia empera in Costa Rica.

PMID- 23157316
TI  - Electrospun nanofiber-based thermite textiles and their reactive properties.
AB  - In this work, we present a first time fabrication of thermite-based nanofiber
      mats with a nitrocellulose composite energetic binder to create a new class of
      energetic 1D nanocomposite. The as prepared thermite based nanofibrous mats were
      characterized and tested for their burning behavior, and compared with the pure
      nitrocellulose and nanoaluminum incorporated nanofibers for their combustion
      performances. Thermite-based nanofibers show enhanced burning rates in combustion
      tests, which correlate to the mass loading of nanothermite relative to binder in
      nanofibers. The electrospinning method demonstrates the possibility of avoiding
      some of the problems associated with melt casting nanometalized propellants.

PMID- 23157317
TI  - CtIP- and ATR-dependent FANCJ phosphorylation in response to DNA strand breaks
      mediated by DNA replication.
AB  - FANCJ, also called BACH1/BRIP1, is a 5'-3' DEAH helicase, whose mutations are
      known as a risk factor for Fanconi anemia and also breast and ovarian cancer.
      FANCJ is thought to contribute to DNA double-strand break (DSB) repair and S
      phase checkpoint through binding to multiple partner proteins, such as BRCA1 and
      TopBP1, but its molecular regulation remains unclear. We focused on DNA damage
      induced phosphorylation of FANCJ and found that reagents that cause DSB or
      replication fork stalling induce FANCJ hyperphosphorylation. In particular,
      camptothecin (CPT) induced rapid and efficient FANCJ hyperphosphorylation that
      was largely dependent on TopBP1 and ATM-Rad3 related (ATR) kinase. Furthermore,
      DNA end resection that exposes single-strand DNA at the DSB site was required for
      hyperphosphorylation. Interestingly, upon CPT treatment, a dramatic increase in
      the FANCJ-TopBP1 complex was observed, and this increase was not alleviated even
      when ATR-dependent hyperphosphorylation was suppressed. These results suggest
      that FANCJ function may be modulated by hyperphosphorylation in a DNA end
      resection- and ATR-dependent manner and by FANCJ-TopBP1 complex formation in
      response to replication-coupled DSBs.

PMID- 23157318
TI  - Gains of ubiquitylation sites in highly conserved proteins in the human lineage.
AB  - BACKGROUND: Post-translational modification of lysine residues of specific
      proteins by ubiquitin modulates the degradation, localization, and activity of
      these target proteins. Here, we identified gains of ubiquitylation sites in
      highly conserved regions of human proteins that occurred during human evolution.
      RESULTS: We analyzed human ubiquitylation site data and multiple alignments of
      orthologous mammalian proteins including those from humans, primates, other
      placental mammals, opossum, and platypus. In our analysis, we identified 281
      ubiquitylation sites in 252 proteins that first appeared along the human lineage
      during primate evolution: one protein had four novel sites; four proteins had
      three sites each; 18 proteins had two sites each; and the remaining 229 proteins
      had one site each. PML, which is involved in neurodevelopment and
      neurodegeneration, acquired three sites, two of which have been reported to be
      involved in the degradation of PML. Thirteen human proteins, including ERCC2
      (also known as XPD) and NBR1, gained human-specific ubiquitylated lysines after
      the human-chimpanzee divergence. ERCC2 has a Lys/Gln polymorphism, the derived
      (major) allele of which confers enhanced DNA repair capacity and reduced cancer
      risk compared with the ancestral (minor) allele. NBR1 and eight other proteins
      that are involved in the human autophagy protein interaction network gained a
      novel ubiquitylation site. CONCLUSIONS: The gain of novel ubiquitylation sites
      could be involved in the evolution of protein degradation and other regulatory
      networks. Although gains of ubiquitylation sites do not necessarily equate to
      adaptive evolution, they are useful candidates for molecular functional analyses
      to identify novel advantageous genetic modifications and innovative phenotypes
      acquired during human evolution.

PMID- 23157320
TI  - A new 20-membered macrolide produced by a marine-derived Micromonospora strain.
AB  - A new 20-membered macrolide named as levantilide C was isolated from the
      Micromonospora strain FIM07-0019 recovered from shallow coastal waters near the
      island of Chiloe, Chile. The chemical structure of levantilide C was elucidated
      on the basis of one- and two-dimensional NMR analysis. Two known indole
      derivatives were also isolated from this strain. Levantilide C exhibited moderate
      antiproliferative activity against several tumour cell lines.

PMID- 23157321
TI  - A pilot study on the sexual side effects of finasteride as related to hand
      preference for men undergoing treatment of male pattern baldness.
AB  - OBJECTIVE: To investigate the relationships between pharmacologically induced
      deprivation of dihydrotestosterone, sexual arousal, libido and hand preference,
      by comparing the self-reported sexual response prior to and during reception of
      the anti-androgen finasteride in men undergoing treatment for male pattern
      baldness. PATIENTS AND METHOD: In total, 33 sexually healthy Romanian men
      participated in this study. Patients prospectively provided information regarding
      their sexual functioning (over 4 weeks), as measured by the International Index
      of Erectile Function (IIEF) prior to and after commencing treatment with 1 mg
      finasteride for male pattern baldness. RESULTS: Overall IIEF scores as well as
      the erectile function, orgasmic function, sexual desire and overall satisfaction
      subscales showed group, treatment and group by treatment effects. The intercourse
      satisfaction subscale showed group and group by treatment effects. On most
      subscales, right-handed men showed no effect or lower sexual function whereas
      left-handed men reported no effect or improved sexual function, primarily.
      CONCLUSIONS: These results suggest that the sexual effects of dihydrotestosterone
      deprivation may depend on handedness--a proxy variable that may represent
      cognitive style--which lends further support to the idea of two distinct
      neuroendocrine psychosexual axes. They further suggest that detection of such
      sexual effects may be enhanced by using research methodologies and communication
      strategies that increase patients' sensitization to such effects.

PMID- 23157319
TI  - The beta 1 tubulin R307H single nucleotide polymorphism is associated with
      treatment failures in immune thrombocytopenia (ITP).
AB  - Predictive biomarkers are needed in immune thrombocytopenia (ITP). Single
      nucleotide polymorphisms (SNPs) in beta 1 tubulin are potential candidates, as
      beta 1 tubulin is integral for platelet production and function, and SNPs in beta
      1 tubulin have been associated with distinct phenotypes in platelets. We
      investigated the most prevalent beta 1 tubulin SNP (R307H) as a biomarker in
      patients with ITP via a retrospective chart review. Allelic frequencies between a
      group of 191 ITP patients and a healthy control group showed no difference,
      suggesting no direct aetiological role for the SNP in ITP. However, over similar
      periods of follow-up, both heterozygote and homozygote minor allele ITP patients
      were treated with significantly more treatment modalities and had significantly
      higher risk of failure to immune-modulatory therapies [relative risk (RR) = 1.5,
      95% confidence interval (CI) = 1.1-2.1; P = 0.01]; with rituximab, in particular,
      ITP patients with the SNP experienced a 58% failure rate (RR = 1.6, 95%CI = 1.03
      2.5; P = 0.04). Analysis of the absolute immature platelet fraction (A-IPF) as a
      marker of platelet production showed that SNP patients had significantly higher
      median A-IPFs compared to non-SNP patients when complete responses were achieved
      using immune modulatory therapies. The data suggest that the beta 1 tubulin R307H
      SNP has potential for use as a biomarker in ITP and may affect platelet turnover.

PMID- 23157322
TI  - The roles of unit leadership and nurse-physician collaboration on nursing
      turnover intention.
AB  - AIM: To report a study of the relationship between variables at the group and
      individual level with nurses' intention to leave their unit. BACKGROUND:
      Workplaces are collective environments where workers constantly interact with
      each other. The quality of working relationship employees develop at the unit
      level influences both employee outcomes and unit performance by shaping employee
      attitudes. DESIGN: The study was a cross-sectional design with self-administered
      questionnaires. METHODS: A questionnaire including measures of leader-member
      exchange and nurse-physician collaboration analysed at group-level and affective
      commitment and turnover intention analysed at individual level, was administered
      individually to 1018 nurses in five Italian hospitals. Data were collected in
      2009. RESULTS: A total of 832 nurses (81.7% response rate) completed
      questionnaires. The results showed that affective commitment at individual level
      completely mediated the relationship between leader-member exchange at group
      level and nursing turnover intention. Furthermore, the cross-level interaction
      was significant: at individual level, the nurses with high levels of individual
      affective commitment towards their unit showed low levels of turnover intention
      and this relationship was stronger when the nurse-physician collaboration at
      group-level was high. CONCLUSION: This study showed the importance for
      organizations to implement management practices that promote both high-quality
      nurse-supervisor and nurse-physician relationships, because they increase nurses'
      identification with their units. Individual affective commitment is an important
      quality for retaining a workforce and good nurses' relationship at group-level
      relationships with both supervisors and physicians are instrumental in developing
      identification with the work unit. Thus, the quality of relationship among staff
      members is an important factor in nurses' decision to leave.

PMID- 23157324
TI  - Hybrid transvaginal and transumbilical laparoendoscopic adnexal surgery.
AB  - BACKGROUND: Natural orifice translumenal endoscopic surgery (NOTES) is an
      emerging concept in the recent literature that could lead to potential benefits
      in clinical applications. The present study describes the initial clinical
      application in 15 cases of hybrid transvaginal and transumbilical NOTES and
      discusses the feasibility, safety, and potential benefits of the method. PATIENTS
      AND METHODS: We evaluated the records of 15 patients who underwent hybrid
      transvaginal and transumbilical laparoendoscopic adnexal surgery between January
      2010 and September 2011. RESULTS: Procedures included salpingo-oophorectomy (n=7)
      and cystectomy (n=3) for ovarian tumors and salpingectomy (n=5) for unruptured
      tubal pregnancy. The mean operative time was 79 minutes (range, 49-116 minutes).
      Blood loss was minimal in all cases. All procedures were successfully performed,
      and there were no conversions to conventional multiport laparoscopy or open
      surgery. Gynecologic examination after 3 months showed no negative findings, and
      the cosmetic result was ideal with no visible scar. CONCLUSIONS: Hybrid
      transvaginal and transumbilical NOTES is feasible and safe in select patients,
      and it provides no visible scar.

PMID- 23157323
TI  - Laparoscopic-assisted "microperc" of a stone in a pelvic kidney of a 3-year-old
      girl.
AB  - Treatment of kidney stones in pelvic ectopic kidneys of children is a challenging
      procedure for urologists. Herein we report a case of laparoscopy-assisted
      "microperc" in a 3-year-old girl with a stone in her pelvic ectopic kidney. This
      micro-optical system is helpful in confirming the percutaneous access and
      provides the possibility of fragmenting the stone without the necessity of
      dilating the tract.

PMID- 23157325
TI  - Laparoscopic pylorus-preserving pancreatoduodenectomy with double jejunal loop
      reconstruction: an old trick for a new dog.
AB  - BACKGROUND: Pancreatoduodenectomy is an established procedure for the treatment
      of benign and malignant diseases located at the pancreatic head and periampullary
      region. In order to decrease morbidity and mortality, we devised a unique
      technique using two different jejunal loops to avoid activation of pancreatic
      juice by biliary secretion and therefore reduce the severity of pancreatic
      fistula. This technique has been used for open pancreatoduodenectomy worldwide
      but to date has never been described for laparoscopic pancreatoduodenectomy. This
      article reports the technique of laparoscopic pylorus-preserving
      pancreatoduodenectomy with two jejunal loops for reconstruction of the alimentary
      tract. MATERIALS AND METHODS: After pancreatic head resection, retrocolic end-to
      side pancreaticojejunostomy with duct-to-mucosa anastomosis is performed. The
      jejunal loop is divided with a stapler, and side-to-side jejunojejunostomy is
      performed with the stapler, leaving a 40-cm jejunal loop for retrocolic
      hepaticojejunostomy. Finally, end-to-side duodenojejunostomy is performed in an
      antecolic fashion. RESULTS: This technique has been successfully used in 3
      consecutive patients with pancreatic head tumors: 2 patients underwent hand
      assisted laparoscopic pylorus-preserving pancreatoduodenectomy, and 1 patient
      underwent totally laparoscopic pylorus-preserving pancreatoduodenectomy. One
      patient presented a Grade A pancreatic fistula that was managed conservatively.
      One patient received blood transfusion. Mean operative time was 9 hours. Mean
      hospital stay was 7 days. No postoperative mortality was observed. CONCLUSIONS:
      Laparoscopic pylorus-preserving pancreatoduodenectomy with double jejunal loop
      reconstruction is feasible and may be useful to decrease morbidity and mortality
      after pancreatoduodenectomy. This operation is challenging and may be reserved
      for highly skilled laparoscopic surgeons.

PMID- 23157327
TI  - Sexual abuse, social stigma and HIV vulnerability among young feminised men in
      Lahore and Karachi, Pakistan.
AB  - This study describes the experiences of 10 young feminised men in Pakistan. They
      face high levels of stigma, violence and sexual abuse. The average age of first
      sex was 11 years old and all reported having been been raped during childhood and
      early adolescence, often several times. While some mothers and siblings were
      quietly supportive, young feminised men often end up running away from home,
      finding support as a member of a hijra dera, a 'pseudo-household' led by an older
      feminised man or guru, in which they find employment as dancers or sex workers.
      After their entry into sex work there is little or no opportunity to use condoms.
      The hijra dera offer an important entry point for improved social support and
      sexual health programmes, including efforts to ensure young feminised men
      postpone their sexual debut and/or improve their sexual health, retain access to
      education, explore alternative forms of employment and improve access to health
      care.

PMID- 23157326
TI  - Multiplexed protease activity assay for low-volume clinical samples using droplet
      based microfluidics and its application to endometriosis.
AB  - As principal degrading enzymes of the extracellular matrix, metalloproteinases
      (MPs) contribute to various pathologies and represent a family of promising drug
      targets and biomarker candidates. However, multiple proteases and endogenous
      inhibitors interact to govern MP activity, often leading to highly context
      dependent protease function that unfortunately has impeded associated clinical
      utility. We present a method for rapidly assessing the activity of multiple
      specific proteases in small volumes (<20 MUL) of complex biological fluids such
      as clinical samples that are available only in very limited amounts. It uses a
      droplet-based microfluidic platform that injects the sample into thousands of
      picoliter-scale droplets from a barcoded droplet library (DL) containing mixtures
      of unique, moderately selective FRET-based protease substrates and specific
      inhibitors and monitors hundreds of the reactions thus initiated simultaneously
      by tracking these droplets. Specific protease activities in the sample are then
      inferred from the reaction rates using a deconvolution technique, proteolytic
      activity matrix analysis (PrAMA). Using a nine-member DL with three inhibitors
      and four FRET substrates, we applied the method to the peritoneal fluid of
      subjects with and without the invasive disease endometriosis. The results showed
      clear and physiologically relevant differences with disease, in particular,
      decreased MMP-2 and ADAM-9 activities.

PMID- 23157329
TI  - Penetration and differentiation of cephalic neural crest-derived cells in the
      developing mouse telencephalon.
AB  - Neural crest (NC) cells originate from the neural folds and migrate into the
      various embryonic regions where they differentiate into multiple cell types. A
      population of cephalic neural crest-derived cells (NCDCs) penetrates back into
      the developing forebrain to differentiate into microvascular pericytes, but
      little is known about when and how cephalic NCDCs invade the telencephalon and
      differentiate into pericytes. Using a transgenic mouse line in which NCDCs are
      genetically labeled with enhanced green fluorescent protein (EGFP), we observed
      that NCDCs started to invade the telencephalon together with endothelial cells
      from embryonic day (E) 9.5. A majority of NCDCs located in the telencephalon
      expressed pericyte markers, that is, PDGFRbeta and NG2, and differentiated into
      pericytes around E11.5. Surprisingly, many of the NC-derived pericytes express
      p75, an undifferentiated NCDC marker at E11.5, as well as NCDCs in the
      mesenchyme. At the same time, a minor population of NCDCs that located separately
      from blood vessels in the telencephalon were NG2-negative and some of these NCDCs
      also expressed p75. Proliferation and differentiation of pericytes appeared to
      occur in a specific mesenchymal region where blood vessels penetrated into the
      telencephalon. These results indicate that (i) NCDCs penetrate back into the
      telencephalon in parallel with angiogenesis, (ii) many NC-derived pericytes may
      be still in pre-mature states even though after differentiation into pericytes in
      the early developing stages, (iii) a small minority of NCDCs may retain
      undifferentiated states in the developing telencephalon, and (iv) a majority of
      NCDCs proliferate and differentiate into pericytes in the mesenchyme around the
      telencephalon.

PMID- 23157328
TI  - Targeted deletion of the antisilencer/enhancer (ASE) element from intron 1 of the
      myelin proteolipid protein gene (Plp1) in mouse reveals that the element is
      dispensable for Plp1 expression in brain during development and remyelination.
AB  - Myelin proteolipid protein gene (Plp1) expression is temporally regulated in
      brain, which peaks during the active myelination period of CNS development.
      Previous studies with Plp1-lacZ transgenic mice demonstrated that (mouse) Plp1
      intron 1 DNA is required for high levels of expression in oligodendrocytes.
      Deletion-transfection analysis revealed the intron contains a single positive
      regulatory element operative in the N20.1 oligodendroglial cell line, which was
      named ASE (antisilencer/enhancer) based on its functional properties in these
      cells. To investigate the role of the ASE in vivo, the element was deleted from
      the native gene in mouse using a Cre/lox strategy. Although removal of the ASE
      from Plp1-lacZ constructs profoundly decreased expression in transfected
      oligodendroglial cell lines (N20.1 and Oli-neu), the element was dispensable to
      achieve normal levels of Plp1 gene expression in mouse during development (except
      perhaps at postnatal day 15) and throughout the remyelination period following
      cuprizone-induced (acute) demyelination. Thus, it is possible that the ASE is non
      functional in vivo, or that loss of the ASE from the native gene in mouse can be
      compensated for by the presence of other regulatory elements within the Plp1
      gene.

PMID- 23157330
TI  - Association of nucleated red blood cells and severity of encephalopathy in
      normothermic and hypothermic infants.
AB  - AIM: To determine whether hypothermia alters the discriminative ability of
      postnatal nucleated red blood cells (NRBCs) to distinguish between mild and
      moderate/severely encephalopathic infants. METHODS: A prospective cohort study
      recruited full-term neonates with hypoxic ischaemic encephalopathy (HIE) from
      2003 to 2012 (prehypothermic and hypothermic eras). The NRBC count was analysed
      in the first 24 h in all infants and compared between normothermic and
      hypothermic cohorts. The severity of encephalopathy was categorized using both
      clinical Sarnat score and continuous multichannel EEG. RESULTS: Eighty-six
      infants with HIE were included: in the normothermic group, 19 were clinically
      mild, 24 moderate/severe; in the hypothermic group, 22 were mild, 21
      moderate/severe encephalopathy. NRBC count discriminated between mild and
      moderate/severe Sarnat scores in the normothermic group (p = 0.03) but not in the
      hypothermic group (p = 0.9). This change was due to a decrease in NRBCs among
      moderately encephalopathic infants in the hypothermic cohort. CONCLUSION:
      Postnatal NRBCs distinguished between mild and moderate/severe encephalopathy in
      normothermic infants but not in infants undergoing therapeutic hypothermia. We
      advise caution when using postnatal blood samples to study diagnostic biomarkers
      for HIE without first analysing the potential impact of hypothermia upon these
      markers.

PMID- 23157331
TI  - Multiple graph regularized protein domain ranking.
AB  - BACKGROUND: Protein domain ranking is a fundamental task in structural biology.
      Most protein domain ranking methods rely on the pairwise comparison of protein
      domains while neglecting the global manifold structure of the protein domain
      database. Recently, graph regularized ranking that exploits the global structure
      of the graph defined by the pairwise similarities has been proposed. However, the
      existing graph regularized ranking methods are very sensitive to the choice of
      the graph model and parameters, and this remains a difficult problem for most of
      the protein domain ranking methods. RESULTS: To tackle this problem, we have
      developed the Multiple Graph regularized Ranking algorithm, MultiG-Rank. Instead
      of using a single graph to regularize the ranking scores, MultiG-Rank
      approximates the intrinsic manifold of protein domain distribution by combining
      multiple initial graphs for the regularization. Graph weights are learned with
      ranking scores jointly and automatically, by alternately minimizing an objective
      function in an iterative algorithm. Experimental results on a subset of the
      ASTRAL SCOP protein domain database demonstrate that MultiG-Rank achieves a
      better ranking performance than single graph regularized ranking methods and
      pairwise similarity based ranking methods. CONCLUSION: The problem of graph model
      and parameter selection in graph regularized protein domain ranking can be solved
      effectively by combining multiple graphs. This aspect of generalization
      introduces a new frontier in applying multiple graphs to solving protein domain
      ranking applications.

PMID- 23157332
TI  - Mechanistic studies of Wacker-type amidocyclization of alkenes catalyzed by
      (IMes)Pd(TFA)2(H2O): kinetic and stereochemical implications of proton transfer.
AB  - The stereochemical course of the amidopalladation of alkenes has important
      implications for the development of enantioselective Pd-catalyzed "Wacker-type"
      oxidative amidation of alkenes. We have recently shown that the addition of base
      (Na2CO3) can alter the stereochemical course of amidopalladation in the
      (IMes)Pd(TFA)2(H2O)-catalyzed aerobic oxidative amidation of alkene. In this
      study, the mechanism of (IMes)Pd(TFA)2(H2O)-catalyzed oxidative heterocyclization
      of (Z)-4-hexenyltosylamide was investigated in the presence and absence of
      exogenous base Na2CO3. The results reveal two parallel pathways in the absence of
      base: a cis-amidopalladation pathway with turnover-limiting deprotonation of the
      sulfonamide nucleophile and a trans-amidopalladation pathway with turnover
      limiting nucleophilic attack of sulfonamide on the coordinated alkene. The
      addition of base (Na2CO3) lowers the energy barrier associated with the proton
      transfer, leading to an overall faster turnover rate and exclusive cis
      amidopalladation of alkene.

PMID- 23157333
TI  - Suppression of phase transition in LiTb(0.01)Mn(1.99)O4 cathodes with fast Li+
      diffusion.
AB  - The structural characteristics of terbium-doped spinel LiTb(x)Mn(2-x)O(4) related
      to the electrochemical performance were studied as the cathode in lithium-ion
      batteries. We chose terbium as the dopant, which is a well-known mixed-valent
      cation (3+/4+), expecting that it would provide structural stabilization and
      improve the power density. LiTb(x)Mn(2-x)O(4) revealed that terbium doping
      significantly affected the lattice structure and lithium-ion diffusion during
      charge-discharge cycles, resulting in an enhanced capacity retention and rate
      capability at an extremely small amount of terbium doping
      (LiTb(0.01)Mn(1.99)O(4)). The absence of two-cubic phase formation in the
      delithiated state and a tetragonal phase in the overlithiated state, along with a
      reduced dimensional change of the main cubic phase during charge-discharge,
      provided LiTb(0.01)Mn(1.99)O(4) with structural stability at both room
      temperature and 60  degrees C. The fast lithium-ion diffusion resulted in reduced
      polarization, which became more conspicuous as the C rates increased. As a
      result, the power density of LiTb(0.01)Mn(1.99)O(4), which was similar to that of
      LiMn(2)O(4) at 1C (476.1 W.kg(-1) for LiMn(2)O(4) vs 487.0 W.kg(-1) for
      LiTb(0.01)Mn(1.99)O(4)), was greatly improved at higher C rates. For example, the
      power density of LiTb(0.01)Mn(1.99)O(4) was improved to 4000 and 6000 W.kg(-1) at
      10 and 20, respectively, compared with 3120 and 3320 W.kg(-1) for pristine
      LiMn(2)O(4).

PMID- 23157334
TI  - Digital imaging in pathology: whole-slide imaging and beyond.
AB  - Digital imaging in pathology has undergone an exponential period of growth and
      expansion catalyzed by changes in imaging hardware and gains in computational
      processing. Today, digitization of entire glass slides at near the optical
      resolution limits of light can occur in 60 s. Whole slides can be imaged in
      fluorescence or by use of multispectral imaging systems. Computational algorithms
      have been developed for cytometric analysis of cells and proteins in subcellular
      locations by use of multiplexed antibody staining protocols. Digital imaging is
      unlocking the potential to integrate primary image features into high-dimensional
      genomic assays by moving microscopic analysis into the digital age. This review
      highlights the emerging field of digital pathology and explores the methods and
      analytic approaches being developed for the application and use of these methods
      in clinical care and research settings.

PMID- 23157336
TI  - Regulation of basement membrane-reactive B cells in BXSB, (NZBxNZW)F1, NZB, and
      MRL/lpr lupus mice.
AB  - Autoantibodies to diverse antigens escape regulation in systemic lupus
      erythematosus under the influence of a multitude of predisposing genes. To gain
      insight into the differential impact of diverse genetic backgrounds on tolerance
      mechanisms controlling autoantibody production in lupus, we established a single
      lupus-derived nephritis associated anti-basement membrane Ig transgene on each of
      four inbred murine lupus strains, including BXSB, (NZBxNZW)F1, NZB, and MRL/lpr,
      as approved by the Duke University and the Durham Veterans Affairs Medical
      Centers' Animal Care and Use Committees. In nonautoimmune C57BL/6 mice, B cells
      bearing this anti-laminin Ig transgene are stringently regulated by central
      deletion, editing, and anergy. Here, we show that tolerance is generally intact
      in unmanipulated Ig transgenic BXSB, (NZBxNZW)F1, and NZB mice, based on absence
      of serum transgenic anti-laminin autoantibodies and failure to recover
      spontaneous anti-laminin monoclonal antibodies. Four- to six-fold depletion of
      splenic B cells in transgenic mice of these strains, as well as in MRL/lpr
      transgenic mice, and reduced frequency of IgM+ bone marrow B cells suggest that
      central deletion is grossly intact. Nonetheless the 4 strains demonstrate
      distinct transgenic B cell phenotypes, including endotoxin-stimulated production
      of anti-laminin antibodies by B cells from transgenic NZB mice, and in vitro
      hyperproliferation of both endotoxin- and BCR-stimulated B cells from transgenic
      BXSB mice, which are shown to have an enrichment of CD21-high marginal zone
      cells. Rare anti-laminin transgenic B cells spontaneously escape tolerance in
      MRL/lpr mice. Further study of the mechanisms underlying these strain-specific B
      cell fates will provide insight into genetic modification of humoral autoimmunity
      in lupus.

PMID- 23157338
TI  - Characterization of myelin pathology in the hippocampal complex of a transgenic
      mouse model of Alzheimer's disease.
AB  - We have characterized the myelin changes observed within the hippocampal complex
      (HC) of a transgenic (Tg) mouse model of Alzheimer's disease (AD). Individual
      myelinated fibers were labeled with Black-Gold II while amyloid plaques were
      labeled with either Congo Red or Pan-A-beta immunofluoresence. Myelinated fibers
      were never seen passing through amyloid plaques in any region, while conspicuous
      myelin pathology was seen within, and immediately adjacent to, the amyloid
      plaques in the HC of the AD-Tg mouse. This pathology consisted of a complete
      disruption of myelinated fibers passing through the plaque and the region
      immediately adjacent to the plaques exhibited an edematous swelling of the
      fibers. This pathology was most frequently observed within the molecular and
      polymorph layers of the dentate gyrus and the molecular layer of Ammon's horn.
      The remaining layers of Ammon's horn exhibited minimal myelin pathology, while
      moderate myelinopathy was observed in the subiculum. Since the HC is integral for
      memory function, these findings may help account for the memory problems so
      characteristic of the disease process. Because the molecular layers of the
      dentate gyrus and Ammon's horn are the sites of inputs to the HC, the extensive
      myelin pathology observed in these regions would imply functional deafferentation
      of the HC. The appearance of some Black-Gold II positive debris within the
      plaques may reflect a possible cascade mechanism whereby the presence of plaques
      results in myelin degeneration, some of which is incorporated within the plaque,
      causing it to further expand in a self-perpetuating fashion.

PMID- 23157337
TI  - Plasma acetylcholinesterase activity correlates with intracerebral beta-amyloid
      load.
AB  - BACKGROUND: Previous studies have demonstrated alterations in the peripheral
      cholinergic system in Alzheimer's disease (AD), though results have been
      inconsistent and not linked to in vivo biomarkers of pathology. We examined the
      relationship between amyloid-beta (Abeta) plaques and plasma cholinesterase
      activity in a heterogeneous dementia population. METHODS: 29 participants with
      clinical AD and 35 with non-AD diagnoses underwent positron emission tomography
      (PET) with the amyloid ligand [11C] PIB and plasma measurements of
      acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) activity. Multi
      linear regression was used to evaluate the relationship between AChE or BChE
      activity and PIB binding (adjusted for age, sex, apolipoprotein E4 and vascular
      risk), applying voxel-wise and region of interest (ROI) approaches. AChE activity
      was further adjusted for cholinesterase inhibitor (ChE-I) use. Global amyloid
      load was measured using a PIB Index, representing mean tracer binding in frontal,
      parietal, lateral temporal and cingulate cortex. RESULTS: AChE activity was
      correlated with PIB Index (beta=0.39, p < 0.001) and with regional PIB binding in
      frontal, temporal, parietal and occipital lobes, precuneus and posterior
      cingulate on both voxel-wise (p < 0.001 uncorrected) and ROI (beta=0.26-0.41, p <
      0.005) analysis. Correlations remained significant after covarying clinical
      diagnosis (beta=0.42, p=0.001), and among participants naive to ChE-I (beta=0.51,
      p=0.005). No correlation was found between BChE activity and PIB. Among AD
      participants, disease severity was not correlated with AChE, BChE or PIB Index.
      CONCLUSION: AChE activity in plasma is correlated with brain Abeta load.
      Activation of the 'anti-inflammatory cholinergic pathway' may provide the link
      between Abeta plaques and peripheral cholinergic measures.

PMID- 23157335
TI  - The Th17 pathway and inflammatory diseases of the intestines, lungs, and skin.
AB  - The recent discovery of a new CD4+ T cell subset, Th17, has transformed our
      understanding of the pathogenetic basis of an increasing number of chronic immune
      mediated diseases. Particularly in tissues that interface with the microbial
      environment-such as the intestinal and respiratory tracts and the skin-where most
      of the Th17 cells in the body reside, dysregulated immunity to self (or the
      extended self, the diverse microbiota that normally colonize these tissues) can
      result in chronic inflammatory disease. In this review, we focus on recent
      advances in the biology of the Th17 pathway and on genome-wide association
      studies that implicate this immune pathway in human disease involving these
      tissues.

PMID- 23157339
TI  - Genetic risk factors for depression in Alzheimer's disease patients.
AB  - OBJECTIVE: Alzheimer's Disease (AD) is often associated with depressive symptoms
      developing at any time before and after AD onset. The aetiology of depression in
      AD has not sufficiently been characterized, but biological aspects due to
      neurodegeneration and/ or genetic risk factors may play a plausible role and may
      distinguish it from common depressive disorders. METHOD: To investigate the
      possible relationship between genetic risk factors and depression in AD, we
      assessed genetic polymorphisms reported to be associated with depression (MAOA
      VNTR, ACE 288bp Insertion/ Deletion, 5HTTLPR, COMT Val158Met, BDNF Val66Met, TPH1
      A218C, HTR2A T102C, P2RX7 Q460R, FKBP5 rs1360780 and CRHR1 rs242941) in a cross
      sectional study on 246 AD patients with or without clinically significant major
      depressive disorder (MDD) according to DSM-IV. RESULTS: Significant associations
      between AD and MDD have been found for three polymorphisms mainly in females
      (TPH1 A218C, MAOA VNTR and BDNF Val66Met) and one polymorphism in the total
      population only (FKBP5 rs1360780). There was an increased risk of having MDD in
      homozygous female carriers of the TPH1 A-allele (odds ratio: 4.35) and homozygous
      carriers of the MAOA VNTR low activity allele 3R (odds ratio: 3.37). CONCLUSION:
      We detected allelic or genotypic associations of MAOA, TPH1, FKBP5 and BDNF in
      clinically significant MDD in AD. Odds-ratios were generally higher in female AD
      patients, which might be due to the composition of the study population. Further
      studies on the neurotransmitter systems affected by the genetic polymorphisms
      found to be associated with MDD in AD may help to elucidate the underlying
      pathomechanisms of MDD.

PMID- 23157340
TI  - Effects of aripiprazole, an atypical antipsychotic, on the motor alterations
      induced by acute ethanol administration in mice.
AB  - Aripiprazole is an antipsychotic that acts as a partial agonist at dopamine
      receptors. As the effects of most drugs of abuse converge to enhance dopamine
      mediated neurotransmission, the present study was designed to test the hypothesis
      that aripiprazole would inhibit the acute effects of ethanol, a widely abused
      substance. Male Swiss mice received acute injections and were evaluated for motor
      activity in three distinct tests. In the open field, ethanol (1.5, 2.5 and 3.5
      g/kg) induced an increase in locomotion in a U-shaped dose-related fashion,
      whereas aripiprazole (0.1, 1 and 10 mg/kg) did not affect this parameter. All the
      doses of the antipsychotic were able to prevent the stimulant effects of 2.5 g/kg
      of ethanol. In the rotarod test, ethanol (2.5 and 3.5 g/kg) reduced the latency
      to fall from the apparatus, an effect also observed with the higher dose of
      aripiprazole. Contrary to what was observed in the open field, this antipsychotic
      did not interfere with the effects of ethanol in motor balance. Finally, we
      tested animals in the wire hang test, in which ethanol, but not aripiprazole,
      reduced latency to fall at all doses. In this test, aripiprazole did not change
      ethanol effects. The present data lead to the conclusion that aripiprazole
      prevents the stimulant effects of ethanol on locomotion, without interfering with
      the motor impairment induced by this drug.

PMID- 23157342
TI  - Novel triterpenoid saponins from the seeds of Celosia argentea L.
AB  - Two new triterpenoid saponins celosin I (1) and celosin II (2) were isolated from
      the seeds of Celosia argentea L. (Amaranthaceae). The structures of the two new
      compounds were elucidated based on chemical analysis and spectral methods (IR, 1
      D and 2-D NMR, ESI-MS, HR-ESI-MS). They exhibited significant hepatoprotective
      effect on carbon tetrachloride-induced and N,N-dimethylformamide-induced
      hepatotoxicity in mice.

PMID- 23157341
TI  - Antitumor properties of natural compounds and related molecules.
AB  - Cancer is the main cause of death in developing countries. Its development
      requires multiple steps in which the occurrence of certain events determines the
      state transition from a normal to a tumor cell. These events are related to the
      loss of mechanisms that control various biological processes, which results from
      the accumulation of genetic alterations, including mutations, chromosomal
      rearrangements, and variations in gene copy number, as well as from epigenetic
      alterations. In general, chemotherapeutic agents used for toxicity treatments
      have shown limited antitumor activity, with a high recurrence rate. This has
      prompted major research efforts to identify novel effective and selective anti
      tumor compounds. In this article, we review recent patents that protect the
      antitumor properties of natural compounds and related molecules derived from
      plants, animals, or microorganisms. We consider their structure, mechanism of
      action, molecular targets and, in some cases, the clinical trial phase reached.
      We also report on various natural agents that appear to prevent cancer
      development.

PMID- 23157343
TI  - Encapsidation of RNA-polyelectrolyte complexes with amphiphilic block copolymers:
      toward a new self-assembly route.
AB  - Amphiphilic block copolymers are molecules composed of hydrophilic and
      hydrophobic segments having the capacity to spontaneously self-assemble into a
      variety of supramolecular structures like micelles and vesicles. Here, we propose
      an original way to self-assemble amphiphilic block copolymers into a supported
      bilayer membrane for defined coating of nanoparticles. The heart of the method
      rests on a change of the amphiphilicity of the copolymer that can be turned off
      and on by varying the polarity of the solvent. In this condition, the assembly
      process can take advantage of specific molecular interactions in both organic
      solvent and water. While the concept potentially could be applied to any type of
      charged substrates, we focus our interest on the design of a new type of polymer
      assembly mimicking the virus morphology. A capsid-like shell of glycoprotein
      mimic amphiphilic block copolymer was self-assembled around a positively charged
      complex of siRNA and polyethyleneimine. The process requires two steps. Block
      copolymers first interact with the complexes dispersed in DMSO through
      electrostatic interactions. Next, the increase of the water content in the medium
      triggers the hydrophobic effect and the concomitant self-assembly of free block
      copolymer molecules into a bilayer membrane at the complex surface. The higher
      gene silencing activity of the copolymer-modified complexes over the complexes
      alone shows the potential of this new type of nanoconstructs for biological
      applications, especially for the delivery of therapeutic biomolecules.

PMID- 23157344
TI  - Poly (glycerol sebacate): a novel scaffold material for temporomandibular joint
      disc engineering.
AB  - The preponderance of temporomandibular joint (TMJ) disorders involving TMJ disc
      injury inspires the need to further explore tissue engineering strategies. The
      objective of this study was to examine the potential of poly (glycerol sebacate)
      (PGS), a biocompatible, biodegradable elastomer, as a porous scaffold material
      for the TMJ disc. Goat fibrochondrocytes were seeded on PGS at three seeding
      densities (25, 50, 100 million cells/mL scaffold), respectively, and cultured for
      24 h, 2 weeks, and 4 weeks. The resulting histological, biochemical, and
      biomechanical properties were determined. Histological staining revealed an
      abundance of both collagen and glycosaminoglycans (GAG) throughout the high
      seeding density scaffolds at 4 weeks. There was also a significant increase in
      the cellular content in all groups over the four-week period, showing that the
      scaffolds promoted cell attachment and proliferation. The PGS scaffolds supported
      the deposition of large quantities of extracellular matrix, with differences
      noted between seeding density groups. At 4 weeks, the medium and high seeding
      density groups had significantly more collagen per scaffold (181+/-46 MUg and
      218+/-24 MUg, respectively) than the low seeding density group (105+/-28 MUg)
      (p<0.001). At 4 weeks, the medium and high seeding density groups also had a
      significantly higher GAG content per scaffold (702+/-253 MUg and 773+/-187 MUg,
      respectively), than the low seeding density group (324+/-73 MUg) (p<0.001). The
      compression tangent modulus was significantly greater at 4 weeks than 24 h
      (123.6+/-86 kPa and 26.2+/-5 kPa, respectively) (seeding density groups combined)
      (p<0.001), with no differences between seeding groups at each time point. After 4
      weeks, the tangent modulus of the low seeding density group was in a similar
      range of the goat TMJ disc (180+/-127 kPa compared to 304+/-141 kPa,
      respectively). The results show that cell seeding density and culture time do
      have an effect on both the biochemical and biomechanical properties of PGS
      scaffolds. These findings demonstrate that PGS has great potential as a scaffold
      material for TMJ disc engineering.

PMID- 23157345
TI  - Boronic acid functionalized boron dipyrromethene fluorescent probes: preparation,
      characterization, and saccharides sensing applications.
AB  - Fluorescent probes based on boron dipyrromethene functionalized with a
      phenylboronic acid group (BODIPY-PBAs) were synthesized in high yield for the
      first time by Suzuki coupling of bis(pinacolato)diboron and 8-(4-bromophenyl)
      1,3,5,7-tetramethyl-4,4-difluoro-4-bora-3a,4a-diaza-s-indacene (BODIPY).
      Wavelength tuning of the fluorophores was achieved by attaching an auxochromic
      substituent to the 5-position of the BODIPY core structure through Knoevenagel
      condensation. The emission intensity of fluorophores increases when binding to
      the analytes with diol groups and forming boronic esters at fixed pH. These
      compounds can detect monosaccharides in the concentration range of 0.1-100 mM.
      Whereas glycogen was found to quench the fluorescence of BODIPY-PBAs in an
      aqueous solution due to the self-quenching of the fluorophores after attaching in
      the extensively branched and compact glucose polymer, further addition of d
      fructose to the solution can release the fluorophores from the polymer and the
      fluorescence regains. The BODIPY-PBA fluorophore has been applied in polymeric
      optodes containing anion exchangers to perform repetitive measurement. Such
      sensors respond to different monosaccharides in the range of 0.1-100 mM and
      demonstrate an improved selectivity toward d-fructose over other saccharides,
      compared to the results obtained from homogeneous assay.

PMID- 23157346
TI  - Nursing intellectual capital theory: operationalization and empirical validation
      of concepts.
AB  - AIMS: To present the operationalization of concepts in the nursing intellectual
      capital theory and the results of a methodological study aimed at empirically
      validating the concepts. BACKGROUND: The nursing intellectual capital theory
      proposes that the stocks of nursing knowledge in an organization are embedded in
      two concepts, nursing human capital and nursing structural capital. The theory
      also proposes that two concepts in the work environment, nurse staffing and
      employer support for nursing continuing professional development, influence
      nursing human capital. DESIGN: A cross-sectional design. METHODS: A systematic
      three-step process was used to operationalize the concepts of the theory. In
      2008, data were collected for 147 inpatient units from administrative departments
      and unit managers in 6 Canadian hospitals. Exploratory factor analyses were
      conducted to determine if the indicator variables accurately reflect their
      respective concepts. RESULTS: The proposed indicator variables collectively
      measured the nurse staffing concept. Three indicators were retained to construct
      nursing human capital: clinical expertise and experience concept. The nursing
      structural capital and employer support for nursing continuing professional
      development concepts were not validated empirically. CONCLUSION: The nurse
      staffing and the nursing human capital: clinical expertise and experience
      concepts will be brought forward for further model testing. Refinement for some
      of the indicator variables of the concepts is indicated. Additional research is
      required with different sources of data to confirm the findings.

PMID- 23157347
TI  - Nerve growth factor-mediated regulation of pain signalling and proposed new
      intervention strategies in clinical pain management.
AB  - Nerve growth factor (NGF) is the founding member of the neurotrophins family of
      proteins. It was discovered more than half a century ago through its ability to
      promote sensory and sympathetic neuronal survival and axonal growth during the
      development of the peripheral nervous system, and is the paradigmatic target
      derived neurotrophic factor on which the neurotrophic hypothesis is based. Since
      that time, NGF has also been shown to play a key role in the generation of acute
      and chronic pain and in hyperalgesia in diverse pain states. NGF is expressed at
      high levels in damaged or inflamed tissues and facilitates pain transmission by
      nociceptive neurons through a variety of mechanisms. Genetic mutations in NGF or
      its tyrosine kinase receptor TrkA, lead to a congenital insensitivity or a
      decreased ability of humans to perceive pain. The hereditary sensory autonomic
      neuropathies (HSANs) encompass a spectrum of neuropathies that affect one's
      ability to perceive sensation. HSAN type IV and HSAN type V are caused by
      mutations in TrkA and NGF respectively. This review will focus firstly on the
      biology of NGF and its role in pain modulation. We will review neuropathies and
      clinical presentations that result from the disruption of NGF signalling in HSAN
      type IV and HSAN type V and review current advances in developing anti-NGF
      therapy for the clinical management of pain.

PMID- 23157348
TI  - Exploitation of genomics in fungicide research: current status and future
      perspectives.
AB  - Every year, fungicide use to control plant disease caused by pathogenic fungi
      increases. The global fungicide market is now worth more than L5.3 billion,
      second only to the herbicide market in importance. In the UK, over 5500 tonnes of
      fungicide were applied to crops in 2010 (The Food and Environment Research
      Agency, Pesticide Usage Statistics), with 95.5% of the wheat-growing area
      receiving three fungicide sprays. Although dependence on fungicides to produce
      food securely, reliably and cheaply may be moderated in the future by further
      developments in crop biotechnology, modern crop protection will continue to
      require a diversity of solutions, including effective and safe chemical control.
      Therefore, investment in exploiting the increasingly available genome sequences
      of the most devastating fungal and oomycete phytopathogenic species should bring
      an array of new opportunities for chemical intervention. To date, the impact of
      whole genome research on the development, introduction and stewardship of
      fungicides has been limited, but ongoing improvements in computational analysis,
      molecular biology, chemical genetics, genome sequencing and transcriptomics will
      facilitate the development and registration of the future suite of crop
      protection chemicals.

PMID- 23157349
TI  - Bioanalysis of biomarkers for drug development.

PMID- 23157350
TI  - Application of commercial research-grade biomarker assays in drug development: is
      it time to create 'pharmaceutical-grade' kits?

PMID- 23157351
TI  - Important considerations for quantitation of small-molecule biomarkers using LC
      MS.

PMID- 23157353
TI  - Recommendations on biomarker bioanalytical method validation by GCC.
AB  - The 5th GCC in Barcelona (Spain) and 6th GCC in San Antonio (TX, USA) events
      provided a unique opportunity for CRO leaders to openly share opinions and
      perspectives, and to agree upon recommendations on biomarker bioanalytical method
      validation.

PMID- 23157354
TI  - Prandial ghrelin attenuation provides evidence that des-acyl ghrelin may be an
      artifact of sample handling in human plasma.
AB  - BACKGROUND: Plasma acyl and des-acyl ghrelin are thought of as components of
      total ghrelin, but this has never been validated using ex vivo spiking
      experiments, human sample collection comparisons and fit-for-purpose translatable
      assays. RESULTS: Acyl ghrelin plasma stability was analyzed by LC-MS/MS and it
      revealed that acyl ghrelin is enzymatically and chemically converted to des-acyl
      ghrelin in the presence of active serine proteases and HCl. ELISAs with less than
      30% total error were used to assess acyl ghrelin behavior in matched authentic
      human samples. Acyl and total ghrelin were not statistically different in 4-(2
      aminoethyl)benzenesulfonyl fluoride hydrochloride samples and acyl ghrelin losses
      in K(2)EDTA plasma were accounted for in des-acyl ghrelin formation. CONCLUSION:
      Acyl ghrelin is total ghrelin and des-acyl ghrelin should not be detectible in
      healthy human plasma under optimal sample handling and assaying conditions.

PMID- 23157356
TI  - Flow cytometry: a flexible tool for biomarker research.
AB  - Flow cytometry is increasingly recognized as an invaluable technology in
      biomarker research. Owing to its multiparametric nature it can provide highly
      detailed information on any single cell in a heterogeneous population. Its
      versatility means it can be conducted in both the preclinical and clinical
      setting, generating biomarker data that can drive decisions pertaining to dose
      selection in clinical trials, treatment options for cancer sufferers and even
      suitability of patients to receive transplants. Most tissue types can be utilized
      by the flow cytometrist, allowing the technology to be applied to many fields of
      research, yet consensus still needs to be reached on standardization, regulation
      and validation of multiparametric flow cytometry assays. In parallel, continual
      innovation in analysis software to manage the huge datasets that can be generated
      is also needed. Nevertheless, the flexibility of flow cytometry means that it
      remains at the forefront of both routine and exploratory biomarker studies.

PMID- 23157355
TI  - Defining putative glycan cancer biomarkers by MS.
AB  - For decades, the association between aberrant glycosylation and many types of
      cancers has been shown. However, defining the changes of glycan structures has
      not been demonstrated until recently. This has been facilitated by the major
      advances in MS and separation science, which allows the detailed characterization
      of glycan changes associated with cancer. MS glycomics methods have been
      successfully employed to compare the glycomic profiles of different human
      specimens collected from disease-free individuals and patients with cancer.
      Additionally, comparing the glycomic profiles of glycoproteins purified from
      specimen collected from disease-free individuals and patients with cancer has
      also been performed. These types of glycan analyses employing MS or LC-MS allow
      the characterization of native, labeled and permethylated glycans. This review
      discusses the different glycomic and glycoproteomic methods employed for defining
      glycans as cancer biomarkers of different organs, including breast, colon,
      esophagus, liver, lung, ovarian, pancreas and prostate.

PMID- 23157357
TI  - Use of PD biomarkers to drive dose selection and early clinical decision making.
AB  - A major challenge facing the development of new therapies is the high level of
      compound attrition in late-stage clinical studies. A key factor in reducing these
      unsustainable levels of attrition is the successful evaluation of the level of
      drug effect on its target pathway in early development, otherwise known as
      testing the compound mechanism. Incorporation of PD biomarkers into Phase I/II
      trials to demonstrate compound binding to its molecular target and the subsequent
      modulation of downstream pathways enables early testing of compound mechanism and
      provides a data-driven framework for decisions on compound progression. This
      review will discuss the identification and validation of such 'fit-for-purpose'
      PD biomarkers, and case studies illustrating their use and value in dose
      selection and accelerating the clinical development of small-molecule drugs will
      be described.

PMID- 23157358
TI  - Genomic biomarkers for patient selection and stratification: the cancer paradigm.
AB  - The revolution in disease diagnosis and treatment promised on the completion of
      the human genome project over a decade ago has materialized in the form of
      unified drug and biomarker discovery and development pipelines. This strategic
      shift has been principally catalyzed through success stories in the field of
      oncology, ushering in the era of personalized medicine. Thus, a number of
      molecular targets have also been demonstrated to be reliable markers for
      selecting patients wherein treatment can be efficacious. Perhaps more
      importantly, however, the late adoption of biomarker strategies has also rescued
      drug candidates from complete late-stage failure. This review examines the
      historical lessons of key challenges in translating biomarker assay information
      into strategic and clinically actionable decisions and assesses the impact of
      personalized genome sequencing in the future of companion diagnostic development
      and commercialization.

PMID- 23157359
TI  - Bioanalysis of target biomarker and PK/PD relevancy during the development of
      biotherapeutics.
AB  - The majority of biotherapeutic drugs act on specific targets, which may serve as
      biomarkers to be evaluated for target engagement and validation. Together with
      subsequent pathway biomarkers, these data can provide proof-of-mechanism and
      understanding of the biological drug affect. A major task during early
      development is to predict, for the first first time in human clinical trials, the
      starting dose and simulate the PK/PD relationship. However, determinations of the
      biotherapeutic drug and target concentrations are not straightforward due to
      temporal changes of drug-target binding and challenges in developing reliable
      methods to measure the free and total drug and target. Herein, the bioanalysis of
      the target biomarker and the biotherapeutics in the context of PK/PD relevancy
      during drug development is reviewed. Binding of the target to the biotherapeutic
      will affect target clearance and drug disposition, resulting in nonlinear PK.
      Reliable and specific methods are crucial for the correct PK/PD modeling and
      interpretation.

PMID- 23157362
TI  - Concise synthesis of the macrocyclic core of rhizopodin by a Heck
      macrocyclization strategy.
AB  - A highly convergent synthesis of the central dimeric core of the potent
      antibiotic macrolide rhizopodin is reported. Notable features of the highly
      concise route include an effective preparation of the key C8-C22 building block
      based on an iridium-catalyzed Krische allylation and a chemoselective cross
      coupling approach toward the macrocycle involving a highly advantageous Heck
      reaction for macrocyclization.

PMID- 23157363
TI  - Electroporation: past, present and future.
AB  - Gene transfer by electroporation has become an indispensable method for the study
      of developmental biology. The technique is applied not only in chick embryos but
      also in mice and other organisms. Here, a short history and perspectives of
      electroporation for gene transfer in vertebrates are described.

PMID- 23157360
TI  - Relative quantification of biomarkers using mixed-isotope labeling coupled with
      MS.
AB  - The identification and quantification of important biomarkers is a critical first
      step in the elucidation of biological systems. Biomarkers take many forms as
      cellular responses to stimuli and can be manifested during transcription,
      translation, and/or metabolic processing. Increasingly, researchers have relied
      upon mixed-isotope labeling (MIL) coupled with MS to perform relative
      quantification of biomarkers between two or more biological samples. MIL
      effectively tags biomarkers of interest for ease of identification and
      quantification within the mass spectrometer by using isotopic labels that
      introduce a heavy and light form of the tag. In addition to MIL coupled with MS,
      a number of other approaches have been used to quantify biomarkers including
      protein gel staining, enzymatic labeling, metabolic labeling, and several label
      free approaches that generate quantitative data from the MS signal response. This
      review focuses on MIL techniques coupled with MS for the quantification of
      protein and small-molecule biomarkers.

PMID- 23157364
TI  - Tuning the properties and functions of 17beta-estradiol-polysaccharide conjugates
      in thin films: impact of sample history.
AB  - In addition to its role in the regulation of sex-related processes, 17beta
      estradiol (E2) participates in the prevention and treatment of cardiovascular
      diseases via nongenomic pathways mediated by estrogen receptors (ER-alpha)
      located in the cell membrane. To achieve specific nongenomic activity of E2, we
      linked E2 (4.4 mol %) to chitosan-phosphorylcholine (CH-PC) (20 mol % PC).
      Injections of ER-alpha solutions (5 to 100 nmol L(-1)) over rehydrated CH-PC-E2
      thin films led to permanent adsorption of ER-alpha to the film surface, as
      detected by quartz crystal microbalance with dissipation (QCM-D). However, ER
      alpha did not bind onto CH-PC-E2 films formed in situ and never dried. X-ray
      photoelectron spectroscopy (XPS) analysis of spin-cast CH-PC-E2 films revealed
      significant E2 enrichment of the topmost section of the film, attributed to the
      preferential migration of E2 toward the film/air interface upon drying.
      Mechanical analysis of CH-PC-E2 films in the frequency domain probed by QCM-D
      indicated that rehydrated films behave as an entangled network with junction
      points formed by self-assembly of hydrophobic E2 moieties and by ion pairing
      among PC groups, whereas films formed in situ are entangled polymer solutions
      with temporary junctions. The structural analysis presented offers useful
      guidelines for the study of amphiphilic biomacromolecules designed for
      therapeutic use as thin films.

PMID- 23157365
TI  - The European Drug Initiative for Channels and Transporters EU project.

PMID- 23157367
TI  - Rhodium-catalyzed allylic substitution with an acyl anion equivalent:
      stereospecific construction of acyclic quaternary carbon stereogenic centers.
AB  - A highly regio- and stereospecific rhodium-catalyzed allylic alkylation of
      tertiary allylic alcohol derivatives with a cyanohydrin pronucleophile is
      described. This direct and operationally simple protocol provides a fundamentally
      novel approach toward the synthesis of alpha-quaternary substituted ketones and
      circumvents many of the inherent problems associated with conventional enolate
      alkylation reactions. The stereospecific variant of this reaction provides the
      enantiomerically enriched alpha-quaternary substituted allylic aryl ketone, which
      is a particularly challenging intermediate for more conventional enolate-based
      strategies.

PMID- 23157368
TI  - The performances of standard and ResMed masks during bag-valve-mask ventilation.
AB  - BACKGROUND: A tight mask seal is frequently difficult to obtain and maintain
      during single-rescuer bag-valve-mask (BVM) ventilation. The ResMed mask (Bella
      Vista, NSW, Australia) is a continuous-positive-airway-pressure mask (CM)
      designed for noninvasive ventilation. OBJECTIVE: In this study, we compared the
      ventilation performances of a standard mask (SM) and a ResMed CM using a
      simulation manikin in an out-of-hospital single-rescuer BVM ventilation scenario.
      METHODS: Thirty emergency medical technicians (EMTs) performed two 2-minute
      attempts to ventilate a simulation manikin using BVM ventilation, alternatively,
      with the SM or the ResMed CM in a randomized order. Ventilation parameters
      including tidal volume and peak airway pressure were measured using computer
      analysis software connected to the simulation manikin. Successful volume delivery
      was defined as delivery of 440-540 mL of tidal volume in accord with present
      cardiopulmonary resuscitation guidelines. RESULTS: BVM ventilation using the
      ResMed CM produced higher mean (+/- standard deviation) tidal volumes (452 +/- 50
      mL vs. 394 +/- 113 mL, p = 0.014) and had a higher proportion of successful
      volume deliveries (65.3% vs. 26.7%, p < 0.001) than that using the SM. Peak
      airway pressure was higher in BVM ventilation using the ResMed CM (p = 0.035).
      Stomach insufflation did not occur during either method. Twenty-nine of the
      participants (96.7%) preferred BVM ventilation using the ResMed CM. CONCLUSIONS:
      BVM ventilations using ResMed CM resulted in a significantly higher proportion of
      successful volume deliveries meeting the currently recommended range of tidal
      volume. Clinical studies are needed to determine the value of the ResMed CM for
      BVM ventilation.

PMID- 23157369
TI  - Persistent genital arousal disorder: characterization, etiology, and management.
AB  - INTRODUCTION: Persistent genital arousal disorder (PGAD) is a potentially
      debilitating disorder of unwanted genital sensation and arousal that is generally
      spontaneous and unrelenting. Since its first description in 2001, many potential
      etiologies and management strategies have been suggested. AIM: To review the
      literature on PGAD, identify possible causes of the disorder, and provide
      approaches to the assessment and treatment of the disorder based on the authors'
      experience and recent literature. METHODS: PubMed searches through July 2012 were
      conducted to identify articles relevant to persistent sexual arousal syndrome and
      PGAD. MAIN OUTCOME MEASURES: Expert opinion was based on review of the medical
      literature related to this subject matter. RESULTS: PGAD is characterized by
      persistent sensations of genital arousal in the absence of sexual stimulation or
      emotion, which are considered unwanted and cause the patient at least moderate
      distress. The proposed etiologies of PGAD are plentiful and may involve a range
      of psychologic, pharmacologic, neurologic, and vascular causes. PGAD has been
      associated with other conditions including overactive bladder and restless leg
      syndrome. Assessment should include a through history and physical exam and
      tailored radiologic studies. Treatment should be aimed at reversible causes,
      whether physiologic or pharmacologic. All patients should be considered for
      cognitive therapy including mindfullness meditation and acceptance therapy.
      CONCLUSIONS: PGAD likely represents a range of conditions manifesting in unwanted
      genital sensations. Successful treatment requires a multidisciplinary approach
      and consideration of all reversible causes as well as cognitive therapy.

PMID- 23157371
TI  - Prospective clinical trial to compare vincristine and vinblastine in a COP-based
      protocol for lymphoma in cats.
AB  - BACKGROUND: Current standard chemotherapy protocols for lymphoma in cats carry
      risks of gastrointestinal toxicity, which can decrease quality of life and
      complicate response assessment. Protocols with less gastrointestinal toxicity may
      improve treatment tolerance. HYPOTHESIS/OBJECTIVES: The study purpose was to
      compare response rate, outcome, and toxicity between cats that received
      vincristine or vinblastine as part of combination chemotherapy for lymphoma. We
      hypothesized that vinblastine would have similar efficacy, but less
      gastrointestinal toxicity, compared with vincristine. ANIMALS: Forty client-owned
      cats with confirmed diagnosis of lymphoma. METHODS: Cats were randomized to 1 of
      2 treatment arms and received weekly COP-based chemotherapy for 6 months or until
      disease progression. Response rate, progression-free survival (PFS), lymphoma
      specific survival (LSS), and incidence and severity of gastrointestinal and
      hematologic toxicity were compared between arms. Arm cross-over occurred if
      specific gastrointestinal toxicity criteria were noted. RESULTS: Cats in both
      arms had similar response rates, PFS, and LSS (48 versus 64 days, P = .87; 139
      versus 136 days, P = .96). Cats that received vincristine were significantly more
      likely to switch arms based on gastrointestinal toxicity than cats that received
      vinblastine (44.4 versus 10.5%, P = .02). Lower baseline weight was significantly
      negatively associated with PFS and LSS (P = .01, P = .003, respectively).
      Baseline anemia was significantly negatively associated with LSS (P = .04).
      CONCLUSIONS AND CLINICAL IMPORTANCE: Results suggest that vinblastine is a
      reasonable alternative to vincristine in the treatment of some cats with
      lymphoma. Baseline body weight remains a significant prognostic factor for cats
      with lymphoma.

PMID- 23157370
TI  - Genome-wide analysis of putative peroxiredoxin in unicellular and filamentous
      cyanobacteria.
AB  - BACKGROUND: Cyanobacteria are photoautotrophic prokaryotes with wide variations
      in genome sizes and ecological habitats. Peroxiredoxin (PRX) is an important
      protein that plays essential roles in protecting own cells against reactive
      oxygen species (ROS). PRXs have been identified from mammals, fungi and higher
      plants. However, knowledge on cyanobacterial PRXs still remains obscure. With the
      availability of 37 sequenced cyanobacterial genomes, we performed a comprehensive
      comparative analysis of PRXs and explored their diversity, distribution, domain
      structure and evolution. RESULTS: Overall 244 putative prx genes were identified,
      which were abundant in filamentous diazotrophic cyanobacteria, Acaryochloris
      marina MBIC 11017, and unicellular cyanobacteria inhabiting freshwater and hot
      springs, while poor in all Prochlorococcus and marine Synechococcus strains.
      Among these putative genes, 25 open reading frames (ORFs) encoding hypothetical
      proteins were identified as prx gene family members and the others were already
      annotated as prx genes. All 244 putative PRXs were classified into five major
      subfamilies (1-Cys, 2-Cys, BCP, PRX5_like, and PRX-like) according to their
      domain structures. The catalytic motifs of the cyanobacterial PRXs were similar
      to those of eukaryotic PRXs and highly conserved in all but the PRX-like
      subfamily. Classical motif (CXXC) of thioredoxin was detected in protein
      sequences from the PRX-like subfamily. Phylogenetic tree constructed of catalytic
      domains coincided well with the domain structures of PRXs and the phylogenies
      based on 16s rRNA. CONCLUSIONS: The distribution of genes encoding PRXs in
      different unicellular and filamentous cyanobacteria especially those sub-families
      like PRX-like or 1-Cys PRX correlate with the genome size, eco-physiology, and
      physiological properties of the organisms. Cyanobacterial and eukaryotic PRXs
      share similar conserved motifs, indicating that cyanobacteria adopt similar
      catalytic mechanisms as eukaryotes. All cyanobacterial PRX proteins share highly
      similar structures, implying that these genes may originate from a common
      ancestor. In this study, a general framework of the sequence-structure-function
      connections of the PRXs was revealed, which may facilitate functional
      investigations of PRXs in various organisms.

PMID- 23157372
TI  - Giant-amplitude, high-work density microactuators with phase transition activated
      nanolayer bimorphs.
AB  - Various mechanisms are currently exploited to transduce a wide range of
      stimulating sources into mechanical motion. At the microscale, simultaneously
      high amplitude, high work output, and high speed in actuation are hindered by
      limitations of these actuation mechanisms. Here we demonstrate a set of
      microactuators fabricated by a simple microfabrication process, showing
      simultaneously high performance by these metrics, operated on the structural
      phase transition in vanadium dioxide responding to diverse stimuli of heat,
      electric current, and light. In both ambient and aqueous conditions, the
      actuators bend with exceedingly high displacement-to-length ratios up to 1 in the
      sub-100 MUm length scale, work densities over 0.63 J/cm(3), and at frequencies up
      to 6 kHz. The functionalities of actuation can be further enriched with
      integrated designs of planar as well as three-dimensional geometries. Combining
      the superior performance, high durability, diversity in responsive stimuli,
      versatile working environments, and microscale manufacturability, these actuators
      offer potential applications in microelectromechanical systems, microfluidics,
      robotics, drug delivery, and artificial muscles.

PMID- 23157373
TI  - Immunogenicity of different hepatitis B virus vaccination schedules in liver
      transplant recipients.
AB  - AIM: To compare the immunogenicity of two modified hepatitis B virus (HBV)
      vaccination schedules in liver transplant recipients. Hepatitis B immunoglobulin
      (HBIG) in combination with nucleoside/nucleotide analogs (NUCs) is the
      recommended prophylaxis for preventing HBV recurrence following liver
      transplantation (LT). However, HBIG treatment is expensive. Active immunization
      with hepatitis B vaccine would be a preferable alternative prophylaxis to replace
      HBIG treatment. However, the overall response rate to standard vaccination (given
      at months 0, 1 and 6) is relatively low in immune-compromised patients. METHODS:
      Two cohorts of 114 subjects were immunized with recombinant HBV vaccine
      containing S-antigen. The patients in the rapid schedule group were immunized
      with 40 MUg HBV vaccine at months 0, 1, 2 and 3, and with 20 MUg at months 4, 5
      and 6. The patients in the accelerated schedule group were immunized with 40 MUg
      of HBV vaccine at days 0, 7, 14 and 28, and 20 MUg at months 2, 3 and 4. RESULTS:
      The overall response rate was 16.7% (19/114) and all responders discontinued HBIG
      injection and only one patient developed HBV recurrence. The response rate was
      24.6% (14/57) and 8.8% (5/57) in the rapid vaccination and the accelerated
      vaccination schedules, respectively (P = 0.024). CONCLUSION: HBV vaccination may
      induce endogenous anti-HBs to replace HBIG in selected patients. Vaccination
      schedules may influence vaccine response, and individual optimization may improve
      response rate to HBV vaccination.

PMID- 23157374
TI  - Selection of appropriate training and validation set chemicals for modelling
      dermal permeability by U-optimal design.
AB  - Quantitative structure-activity relationship (QSAR) models are being used
      increasingly in skin permeation studies. The main idea of QSAR modelling is to
      quantify the relationship between biological activities and chemical properties,
      and thus to predict the activity of chemical solutes. As a key step, the
      selection of a representative and structurally diverse training set is critical
      to the prediction power of a QSAR model. Early QSAR models selected training sets
      in a subjective way and solutes in the training set were relatively homogenous.
      More recently, statistical methods such as D-optimal design or space-filling
      design have been applied but such methods are not always ideal. This paper
      describes a comprehensive procedure to select training sets from a large
      candidate set of 4534 solutes. A newly proposed 'Baynes' rule', which is a
      modification of Lipinski's 'rule of five', was used to screen out solutes that
      were not qualified for the study. U-optimality was used as the selection
      criterion. A principal component analysis showed that the selected training set
      was representative of the chemical space. Gas chromatograph amenability was
      verified. A model built using the training set was shown to have greater
      predictive power than a model built using a previous dataset [1].

PMID- 23157375
TI  - Brief but chronic increase in allopregnanolone cause accelerated AD pathology
      differently in two mouse models.
AB  - Previously, we have shown that chronic treatment with allopregnanolone (ALLO) for
      three months impaired learning function in the Swe/PS1 mouse model. ALLO is a
      neurosteroid, produced in the CNS and a GABAA receptor agonist. ALLO modulates
      the general inhibitory system in the CNS by enhancing the effect of GABA. Chronic
      treatment with other GABAA receptor active compounds, such as benzodiazepines,
      ethanol and medroxy-progesterone acetate has been associated to cognitive decline
      and/or increased risk for dementia. In this study, we sufficed with a treatment
      period of one month for the Swe/PS1 mouse, and included another Alzheimer's
      disease mouse model; the Swe/Arc model. We found that one month of chronic
      treatment with elevated ALLO levels within physiological range impaired learning
      and memory function in the Swe/Arc female and male mice. Male Swe/PS1 mice also
      showed marginally impaired function, while the female mice did not. Furthermore,
      the chronic ALLO treatment caused increased levels of soluble Abeta in the
      Swe/PS1 mouse model while the levels were unchanged in the Swe/Arc model.
      Therefore, both Swe/Arc and Swe/PS1 mice showed signs of accelerated disease
      progression. Still, further studies are required to determine the mechanisms
      behind the cognitive impairment and the increased Abeta-levels caused by mildly
      elevated ALLO-levels.

PMID- 23157376
TI  - Efficacy and adverse effects of venlafaxine in children and adolescents with
      ADHD: a systematic review of non-controlled and controlled trials.
AB  - Attention deficit hyperactivity disorder (ADHD) is a common psychiatric disorder
      in children and adolescents. Stimulants are commonly prescribed for ADHD
      management. There is clinical trial evidence that some medications with
      noradrenergic properties such as atomoxetine are effective. It is of theoretical
      and practical importance if other agents with noradrenergic properties display a
      comparable pattern of efficacy. This paper is a systematic review of the efficacy
      and safety of venlafaxine for treating children and adolescents with ADHD.
      MEDLINE, Google scholar, Scopus, and Web of science (ISI) databases were
      electronically searched in July 2012, updated on November 2012. Time and language
      of publication were not exclusion criteria. Efficacy outcomes were assessed by a
      valid and reliable parent- and/or teacher-reported instrument to evaluate
      clinical symptoms. Adverse effects were also evaluated. There were three
      uncontrolled trials and only two double blind controlled clinical trials.
      Venlafaxine appeared effective for treating ADHD. The rates of some adverse
      effects of venlafaxine were less than those documented for methylphenidate. While
      one of the two small controlled trials did not find difference between
      venlafaxine ad methylphenidate, the other trial reported lower efficacy for
      venlafaxine. Headache, insomnia, and nausea were among the most common adverse
      effects. This systematic review provides preliminary support that venlafaxine may
      have short term utility in treating ADHD in children and adolescents. However,
      before recommending venlafaxine for treatment, more robust and larger clinical
      trials, in particular providing evidence of its long-term efficacy, safety and
      tolerability are required.

PMID- 23157377
TI  - FAD/folate-dependent tRNA methyltransferase: flavin as a new methyl-transfer
      agent.
AB  - RNAs contain structurally and functionally important modified nucleosides.
      Methylation, the most frequent RNA modification in all living organisms, mostly
      relies on SAM (S-adenosylmethionine)-dependent methyltransferases. TrmFO was
      recently discovered as a unique tRNA methyltransferase using instead
      methylenetetrahydrofolate and reduced flavin adenine dinucleotide (FAD) as
      essential cofactors, but its mechanism has remained elusive. Here, we report that
      TrmFO carries an active tRNA-methylating agent and characterize it as an original
      enzyme-methylene-FAD covalent adduct by mass spectrometry and a combination of
      spectroscopic and biochemical methods. Our data support a novel tRNA methylating
      mechanism.

PMID- 23157378
TI  - Betaine attenuates Alzheimer-like pathological changes and memory deficits
      induced by homocysteine.
AB  - Hyperhomocysteinemia (Hhcy) may induce memory deficits with beta-amyloid (Abeta)
      accumulation and tau hyperphosphorylation. Simultaneous supplement of folate and
      vitamin B12 partially restored the plasma homocysteine level and attenuated tau
      hyperphosphorylation, Abeta accumulation and memory impairments induced by Hhcy.
      However, folate and vitamin B12 treatment have no effects on Hhcy which has the
      methylenetetrahydrofolate reductase genotype mutation. In this study, we
      investigated the effects of simultaneous supplement of betaine on Alzheimer-like
      pathological changes and memory deficits in hyperhomocysteinemic rats after a 2
      week induction by vena caudalis injection of homocysteine (Hcy). We found that
      supplementation of betaine could ameliorate the Hcy-induced memory deficits,
      enhance long-term potentiation (LTP) and increase dendritic branches numbers and
      the density of the dendritic spines, with up-regulation of NR1, NR2A,
      synaptotagmin, synaptophysin, and phosphorylated synapsin I protein levels.
      Supplementation of betaine also attenuated the Hcy-induced tau
      hyperphosphorylation at multiple AD-related sites through activation protein
      phosphatase-2A (PP2A) with decreased inhibitory demethylated PP2A(C)  at Leu309
      and phosphorylated PP2A(C)  at Tyr307. In addition, supplementation of betaine
      also decreased Abeta production with decreased presenilin-1 protein levels. Our
      data suggest that betaine could be a promising candidate for arresting Hcy
      induced AD-like pathological changes and memory deficits.

PMID- 23157379
TI  - Development of a three-dimensional bone-like construct in a soft self-assembling
      peptide matrix.
AB  - This work describes the development of a three-dimensional (3D) model of
      osteogenesis using mouse preosteoblastic MC3T3-E1 cells and a soft synthetic
      matrix made out of self-assembling peptide nanofibers. By adjusting the matrix
      stiffness to very low values (around 120 Pa), cells were found to migrate within
      the matrix, interact forming a cell-cell network, and create a contracted and
      stiffer structure. Interestingly, during this process, cells spontaneously
      upregulate the expression of bone-related proteins such as collagen type I, bone
      sialoprotein, and osteocalcin, indicating that the 3D environment enhances their
      osteogenic potential. However, unlike MC3T3-E1 cultures in 2D, the addition of
      dexamethasone is required to acquire a final mature phenotype characterized by
      features such as matrix mineralization. Moreover, a slight increase in the
      hydrogel stiffness (threefold) or the addition of a cell contractility inhibitor
      (Rho kinase inhibitor) abrogates cell elongation, migration, and 3D culture
      contraction. However, this mechanical inhibition does not seem to noticeably
      affect the osteogenic process, at least at early culture times. This 3D bone
      model intends to emphasize cell-cell interactions, which have a critical role
      during tissue formation, by using a compliant unrestricted synthetic matrix.

PMID- 23157380
TI  - The intraprofessional and interprofessional relations of neurorehabilitation
      nurses: a negotiated order perspective.
AB  - AIMS: To report a study of the negotiation practices of neurorehabilitation
      nurses with one another and with allied health professionals to understand
      nursing relations. BACKGROUND: Negotiated order theory offers a promising
      theoretical lens with which to explore negotiation between nurses and other
      professionals. This study is the first to apply the perspective to nurse-nurse
      and nurse-allied health professional relations. DESIGN: The study is a secondary
      analysis of findings from a multi-site arts-based intervention to improve patient
      centred neurorehabilitation practice. METHODS: Interviews and ethnographic
      observations were conducted (2008-2011) in two neurorehabilitation units in
      Ontario, Canada. Participants (n = 31) included registered and practical nurses,
      nurse leaders, and allied health professionals from physical, occupational, and
      recreational therapy, speech language pathology, and social work. FINDINGS:
      Neurorehabilitation nursing is characterized by heavy workload, high patient
      acuity, and poor interprofessional collaboration. This practice context was
      negotiated by nurses through two strategies: (1) intraprofessional collegialism,
      accomplished through tactics including task and knowledge sharing, emotional
      support, coercive threats, and suppression of dissension; and (2) vying for an
      autonomous essential nursing role in interprofessional practice, accomplished by
      claiming unique nursing knowledge based on 24/7 nursing proximity, the expansion
      of the division of professional labour with allied health professionals and
      modifying physical therapy care plans. CONCLUSION: The intraprofessional context
      and negotiations therein were linked in significant ways to interprofessional
      negotiations. Understanding this complexity has important implications for
      improving patient safety and interprofessional practice interventions.

PMID- 23157381
TI  - Colored medaka and zebrafish: transgenics with ubiquitous and strong transgene
      expression driven by the medaka beta-actin promoter.
AB  - Conditional cell labeling, cell tracing, and genetic manipulation approaches are
      becoming increasingly important in developmental and regenerative biology. Such
      approaches in zebrafish research are hampered by the lack of an ubiquitous
      transgene driver element that is active at all developmental stages. Here, we
      report the isolation and characterization of the medaka fish (Oryzias latipes)
      beta-actin (Olactb) promoter, which drives constitutive transgene expression
      during all developmental stages, and the analysis of adult organs except blood
      cell types. Taking advantage of the compact medaka promoter, we succeeded in
      generating a zebrafish transgenic (Tg) line with unprecedentedly strong and
      widespread transgene expression from embryonic to adult stages. Moreover, the Tg
      carries a pair of loxP sites, which enables the reporter fluorophore to switch
      from DsRed2 to enhanced green fluorescent protein (EGFP). We induced Cre/loxP
      recombination with Tg(hsp70l: mCherry-t2a-Cre(ERt2) ) in the double Tg embryo and
      generated a Tg line that constitutively expresses EGFP. We further demonstrate
      the powerful application of Olactb-driven Tgs for cell lineage tracing using
      transplantation experiments with embryonic cells at the shield stage and adult
      cells of regenerating fin. Thus, the use of promoter elements from medaka is an
      alternative approach to generate Tgs with stronger and even novel expression
      patterns in zebrafish. The Olactb promoter and the Tg lines presented here
      represent an important advancement for the broader use of Cre/loxP-based Tg
      applications in zebrafish.

PMID- 23157383
TI  - Direct observation of conformation-dependent pathways in the excited-state proton
      transfer of 7-hydroxyquinoline in bulk alcohols.
AB  - The excited-state proton transfer (ESPT) of 7-hydroxyquinoline (7HQ) in bulk
      alcoholic solvents has been explored with variation of protic hydrogen atoms as
      well as alcohols. By measuring time-resolved kinetic profiles at two different
      excitation wavelengths, we have observed conformation-specific pathways in the
      ESPT of 7HQ. There are two possible rotamers of 7HQ according to the
      configuration of its hydroxyl group, which are trans and cis. On one hand, trans
      7HQ cannot undergo proton transfer within its excited-state lifetime because the
      internal rotation of the hydroxyl group to form cis-7HQ hardly occurs. On the
      other hand, some cis-7HQ molecules exist as cyclic complexes of 7HQ.(alcohol)(2)
      at the moment of excitation, and the cyclic complexes can undergo ESPT rapidly
      via tunneling. However, the other cis-7HQ molecules should undergo solvent
      reorganization to form cyclic 7HQ.(alcohol)(2) complexes prior to intrinsic ESPT,
      and the solvent reorganization becomes the rate-determining step. In contrast to
      proton transfer, where intrinsic ESPT and solvent reorganization have been
      observed separately in time-resolved kinetic profiles, intrinsic deuteron
      transfer is too slow to be distinguished kinetically from solvent reorganization.

PMID- 23157384
TI  - Different fates of Alzheimer's disease amyloid-beta fibrils remodeled by
      biocompatible small molecules.
AB  - Amyloid fibrils implicated in numerous human diseases are thermodynamically very
      stable. Stringent conditions that would not be possible in a physiological
      environment are often required to disrupt the stable fibrils. Recently, there is
      increasing evidence that small molecules can remodel amyloid fibrils in a
      physiologically relevant manner. In order to investigate possible fibril
      remodeling mechanisms using this approach, we performed comparative studies on
      the structural features of the different amyloid-beta (Abeta) aggregates
      remodeled from Abeta fibrils by three biocompatible small molecules: methylene
      blue; brilliant blue G; and erythrosine B. Combined with circular dichroism (CD),
      immuno-blotting, transmission electron microscopy (TEM), and atomic force
      microscopy (AFM) results, it was found that brilliant blue G- and erythrosine B
      treatment generate fragmented Abeta fibrils and protofibrils, respectively. In
      contrast, incubation of the Abeta fibrils with methylene blue perturbs fibrillar
      structure, leading to amorphous Abeta aggregates. Our findings provide insights
      on the molecular mechanism of amyloid fibril formation and remodeling and also
      illustrate the possibility of controlled changes in biomolecule nanostructures.

PMID- 23157386
TI  - The seaweed holobiont: understanding seaweed-bacteria interactions.
AB  - Seaweeds (macroalgae) form a diverse and ubiquitous group of photosynthetic
      organisms that play an essential role in aquatic ecosystems. These ecosystem
      engineers contribute significantly to global primary production and are the major
      habitat formers on rocky shores in temperate waters, providing food and shelter
      for aquatic life. Like other eukaryotic organisms, macroalgae harbor a rich
      diversity of associated microorganisms with functions related to host health and
      defense. In particular, epiphytic bacterial communities have been reported as
      essential for normal morphological development of the algal host, and bacteria
      with antifouling properties are thought to protect chemically undefended
      macroalgae from detrimental, secondary colonization by other microscopic and
      macroscopic epibiota. This tight relationship suggests that macroalgae and
      epiphytic bacteria interact as a unified functional entity or holobiont,
      analogous to the previously suggested relationship in corals. Moreover, given
      that the impact of diseases in marine ecosystems is apparently increasing,
      understanding the role of bacteria as saprophytes and pathogens in seaweed
      communities may have important implications for marine management strategies.
      This review reports on the recent advances in the understanding of macroalgal
      bacterial interactions with reference to the diversity and functional role of
      epiphytic bacteria in maintaining algal health, highlighting the holobiont
      concept.

PMID- 23157387
TI  - AsnB, regulated by diffusible signal factor and global regulator Clp, is involved
      in aspartate metabolism, resistance to oxidative stress and virulence in
      Xanthomonas oryzae pv. oryzicola.
AB  - Xanthomonas oryzae pv. oryzicola (Xoc) causes bacterial leaf streak in rice,
      which is a destructive disease worldwide. Xoc virulence factors are regulated by
      diffusible signal factor (DSF) and the global regulator Clp. In this study, we
      have demonstrated that asnB (XOC_3054), encoding an asparagine synthetase, is a
      novel virulence-related gene regulated by both DSF and Clp in Xoc. A sequence
      analysis revealed that AsnB is highly conserved in Xanthomonas. An asnB mutation
      in Xoc dramatically impaired pathogen virulence and growth rate in host rice, but
      did not affect the ability to trigger the hypersensitive response in nonhost
      (plant) tobacco. Compared with the wild-type strain, the asnB deletion mutant was
      unable to grow in basic MMX (-) medium (a minimal medium without ammonium
      sulphate as the nitrogen source) with or without 10 tested nitrogen sources,
      except asparagine. The disruption of asnB impaired pathogen resistance to
      oxidative stress and reduced the transcriptional expression of oxyR, katA and
      katG, which encode three important proteins responsible for hydrogen peroxide
      (H(2)O(2)) sensing and detoxification in Xanthomonas in the presence of H(2)O(2),
      and nine important known Xoc virulence-related genes in plant cell-mimicking
      medium. Furthermore, the asnB mutation did not affect extracellular protease
      activity, extracellular polysaccharide production, motility or chemotaxis. Taken
      together, our results demonstrate the role of asnB in Xanthomonas for the first
      time.

PMID- 23157388
TI  - JACOB: a dynamic database for computational chemistry benchmarking.
AB  - JACOB (just a collection of benchmarks) is a database that contains four diverse
      benchmark studies, which in-turn included 72 data sets, with a total of 122,356
      individual results. The database is constructed upon a dynamic web framework that
      allows users to retrieve data from the database via predefined categories.
      Additional flexibility is made available via user-defined text-based queries.
      Requested sets of results are then automatically presented as bar graphs, with
      parameters of the graphs being controllable via the URL. JACOB is currently
      available at www.wallerlab.org/jacob.

PMID- 23157389
TI  - Effects of thrombopoietin on growth of hepatocellular carcinoma: Is
      thrombopoietin therapy for liver disease safe or not?
AB  - AIM: Liver cirrhosis (LC) is the end stage of chronic liver disease. No
      definitive pharmacological treatment is currently available. We previously
      reported that thrombopoietin (TPO) promoted liver regeneration and improved liver
      cirrhosis by increasing platelet count. TPO is therefore considered to be a
      therapeutic agent for LC; however, it is unclear whether TPO has proliferative
      effects on hepatocellular carcinoma (HCC), which arises frequently in cirrhotic
      livers. In this study, we examined the effects of TPO on growth of HCC. METHODS:
      Expression of the TPO receptor, myeloproliferative leukemia virus oncogene (MPL)
      was examined in various liver tumor cell lines and liver cell types. In an in
      vitro study, the effects of TPO on signal transduction, cell proliferation,
      migration and invasion were examined in Huh7 cells, in which MPL is highly
      expressed. In an in vivo study, we subcutaneously transplanted Huh7 cells into
      nude mice that were divided into a TPO-treated group and a control group, and the
      tumor volume of each group was measured. RESULTS: MPL was expressed strongly in
      hepatocytes but not in other cell types. Among liver tumor cell lines, Huh7
      showed the highest expression of MPL. In Huh7, the addition of TPO activated Akt
      phosphorylation but not cell proliferation, migration or invasion. In the mouse
      experiment, there was no significant difference in tumor volume between the two
      groups. CONCLUSION: TPO had no proliferative effect on HCC in vitro or in vivo,
      and could therefore be useful in the treatment of liver cirrhosis.

PMID- 23157382
TI  - Proteomics-based methods for discovery, quantification, and validation of protein
      protein interactions.

PMID- 23157390
TI  - Construction of a highly flexible and comprehensive gene collection representing
      the ORFeome of the human pathogen Chlamydia pneumoniae.
AB  - BACKGROUND: The Gram-negative bacterium Chlamydia pneumoniae (Cpn) is the leading
      intracellular human pathogen responsible for respiratory infections such as
      pneumonia and bronchitis. Basic and applied research in pathogen biology,
      especially the elaboration of new mechanism-based anti-pathogen strategies,
      target discovery and drug development, rely heavily on the availability of the
      entire set of pathogen open reading frames, the ORFeome. The ORFeome of Cpn will
      enable genome- and proteome-wide systematic analysis of Cpn, which will improve
      our understanding of the molecular networks and mechanisms underlying and
      governing its pathogenesis. RESULTS: Here we report the construction of a
      comprehensive gene collection covering 98.5% of the 1052 predicted and verified
      ORFs of Cpn (Chlamydia pneumoniae strain CWL029) in Gateway((r)) 'entry' vectors.
      Based on genomic DNA isolated from the vascular chlamydial strain CV-6, we
      constructed an ORFeome library that contains 869 unique Gateway((r)) entry clones
      (83% coverage) and an additional 168 PCR-verified 'pooled' entry clones, reaching
      an overall coverage of ~98.5% of the predicted CWL029 ORFs. The high quality of
      the ORFeome library was verified by PCR-gel electrophoresis and DNA sequencing,
      and its functionality was demonstrated by expressing panels of recombinant
      proteins in Escherichia coli and by genome-wide protein interaction analysis for
      a test set of three Cpn virulence factors in a yeast 2-hybrid system. The ORFeome
      is available in different configurations of resource stocks, PCR-products,
      purified plasmid DNA, and living cultures of E. coli harboring the desired entry
      clone or pooled entry clones. All resources are available in 96-well
      microtiterplates. CONCLUSION: This first ORFeome library for Cpn provides an
      essential new tool for this important pathogen. The high coverage of entry clones
      will enable a systems biology approach for Cpn or host-pathogen analysis. The
      high yield of recombinant proteins and the promising interactors for Cpn
      virulence factors described here demonstrate the possibilities for proteome-wide
      studies.

PMID- 23157391
TI  - Recurrent pediatric central nervous system low-grade gliomas: the role of
      surveillance neuroimaging in asymptomatic children.
AB  - OBJECT: Pediatric low-grade glioma (LGG) is the most common brain tumor of
      childhood. Except for the known association of gross-total resection and improved
      survival rates, relatively little is known about the clinical and radiographic
      predictors of recurrent disease and the optimal frequency of surveillance MRI.
      The authors sought to determine the clinical and radiographic features associated
      with recurrent or progressive disease in a single-institutional series of
      children diagnosed with primary CNS LGG. METHODS: The authors performed a
      retrospective analysis of data obtained in 102 consecutive patients diagnosed at
      Rady Children's Hospital-San Diego between 1994 and 2010 with a biopsy-proven LGG
      exclusive of a diagnosis of neurofibromatosis. Tumor location, patient age, sex,
      and symptomatology were correlated with tumor progression or recurrence. Magnetic
      resonance imaging characteristics and neuroimaging surveillance frequency were
      analyzed in those children with progressive or recurrent disease. RESULTS: Forty
      six of 102 children diagnosed with an LGG had evidence of recurrent or
      progressive disease between 2 months and 11 years (mean 27.3 months) after
      diagnosis. In the larger group of 102 children, gross-total resection was
      associated with improved progression-free survival (p = 0.012). The location of
      tumor (p = 0.26), age at diagnosis (p = 0.69), duration of symptoms (p = 0.72),
      histological subtype (p = 0.74), sex (p = 0.53), or specific chemotherapeutic
      treatment regimen (p = 0.24) was not associated with tumor progression or
      recurrence. Sixty-four percent of children with recurrent or progressive disease
      were asymptomatic, and recurrence was diagnosed by surveillance MRI alone. All
      children less than 2 years of age in whom the tumor was diagnosed were
      asymptomatic at the time of progression (p = 0.04). Thirteen percent (6 of 46) of
      the children had disease recurrence 5 years after initial diagnosis; all of them
      had undergone an initial subtotal resection. Tumor progression was associated
      with either homogeneous or patchy T1-weighted post-Gd administration MRI
      enhancement in 94% of the cases (p = 0.0001). CONCLUSIONS: Children diagnosed
      with recurrent LGG may be asymptomatic at the time of recurrence. The authors'
      findings support the need for routine neuroimaging in a subset of children with
      LGGs, even when gross-total resection has been achieved, up to 5 years
      postdiagnosis. The authors found that T1-weighted MR images obtained before and
      after Gd administration alone may be sufficient to diagnose LGG recurrence and
      may represent an effective strategy worthy of further validation in a larger
      multiinstitutional cohort.

PMID- 23157392
TI  - Spinal level of myelomeningocele lesion as a contributing factor in posterior
      fossa volume, intracranial cerebellar volume, and cerebellar ectopia.
AB  - OBJECT: McLone and Knepper's unified theory of Chiari malformation Type II (CM
      II) describes how the loss of CSF via the open posterior neuropore fails to
      create adequate distending pressure for the developing rhomboencephalic vesicle.
      The authors of the present article describe the relationship between the
      posterior fossa volume and intracranial cerebellar volume as being related to the
      distance from the obex of the fourth ventricle to the myelomeningocele lesion
      using a common mathematical model, the Hagen-Poiseuille law. METHODS: All
      newborns who required closure of a myelomeningocele at the authors' institution
      between 2008 and 2011 and who were between 4 weeks premature and 2 months,
      corrected gestational age, at the time of MRI were included in this study.
      Volumes and measurements were obtained from axial and sagittal T2-weighted MR
      images of the brain and spine. RESULTS: A total of 56 newborn infants met the
      inclusion criteria. There was a direct linear relationship between both posterior
      fossa volume and cerebellar volume and the spinal level of the myelomeningocele
      lesion (p = 0.0012 and p = 0.0041, respectively). There was a negative linear
      relationship between the cerebellar descent, the spinal level of the lesion, and
      posterior fossa volume and cerebellar volume. These relationships strengthen in
      patients with no syringomyelia and are not significant in those groups with
      syringomyelia. The results of a 1-way ANOVA for the 3 groups did not reach
      significance. CONCLUSIONS: Using a linear equation derived from the Hagen
      Poiseuille law that describes pressure in the fourth ventricle as being directly
      related to the length of the central canal from the obex to the myelomeningocele
      lesion, the authors were able to explain the directly observed linear relation
      between posterior fossa volume, intracranial cerebellar volume, and cerebellar
      descent to the level of the spinal lesion. As this model assumes a uniform radius
      of the central canal they were able to validate this model when they observed a
      strengthening in relationships in the no syringomyelia group and statistically
      insignificant correlations in the groups with syringomyelia. They therefore
      propose that the spinal level of the lesion is one of the major determinants of
      posterior fossa volume, intracranial cerebellar volume, and cerebellar ectopia.

PMID- 23157393
TI  - Meconium staining of the brainstem with open myelomeningocele.
AB  - Meconium staining of open myelomeningoceles has been reported to occur both
      prenatally and postnatally, but meconium staining of the brainstem has not been
      previously documented. The authors present a case of meconium staining of the
      brainstem in an infant with a meconium-stained myelomeningocele, Chiari
      malformation Type II, and hydrocephalus and discuss possible implications for
      prenatal and perinatal care.

PMID- 23157394
TI  - Occipitocervical fusion using a contoured rod and wire construct in children: a
      reappraisal of a vintage technique.
AB  - OBJECT: Many methods to stabilize and fuse the craniocervical junction have been
      described. One of the early designs was a contoured (Luque) rod fixated with
      wires, the so-called Hartshill-Ransford loop. In this study, the authors report
      their 20-year experience with this surgical technique in children. METHODS: The
      authors reviewed the medical records of patients 18 years of age or younger who
      underwent dorsal occipitocervical fusion procedures between March 1992 and March
      2012 at Le Bonheur Children's Hospital using a contoured rod and wire construct.
      Data on basic patient characteristics, causes of instability, neurological
      function at presentation and at last follow-up, details of surgery,
      complications, and radiographic outcome were collected. RESULTS: Twenty patients
      (11 male) were identified, with a mean age of 5.5 years (range 1-18 years) and a
      median follow-up of 43.5 months. Fourteen patients had atlantooccipital
      dislocation, 2 patients had atlantoaxial fracture-dissociations, 2 had Down
      syndrome with occipitocervical and atlantoaxial instability, 1 had an epithelioid
      sarcoma from the clivus to C-2, and 1 had an anomalous atlas with resultant
      occipitocervical instability. Surgical stabilization extended from the occiput to
      C-1 in 3 patients, C-2 in 6, C-3 in 8, and to C-4 in 3. Bone morphogenetic
      protein was used in 2 patients. Two patients were placed in a halo orthosis; the
      rest were kept in a hard collar for 6-8 weeks. All patients were neurologically
      stable after surgery. One patient with a dural tear experienced wound dehiscence
      with CSF leakage and required reoperation. Eighteen patients went on to achieve
      fusion within 6 months of surgery; 1 patient was initially lost to follow-up, but
      recent imaging demonstrated a solid fusion. There were no early hardware or bone
      failures requiring hardware removal, but radiographs obtained 8 years after
      surgery showed that 1 patient had an asymptomatic fractured rod. There were no
      instances of symptomatic junctional degeneration, and no patient was found to
      have increasing lordosis over the fused segments. Five (31%) of the 16 trauma
      patients required a shunt for hydrocephalus. CONCLUSIONS: Despite the
      proliferation of screw-fixation techniques for craniocervical instability in
      children, the contoured rod-wire construct remains an effective, less expensive,
      and technically easier alternative that has been in use for almost 30 years. It
      confers immediate stability, and therefore most patients will not need to be
      placed in a halo device postoperatively. A secondary observation in our series
      was the high (30%) rate of hydrocephalus requiring a shunt in patients with
      traumatic instability.

PMID- 23157395
TI  - Postshunting corpus callosum swelling with depiction on tractography.
AB  - Alterations in the appearance of the corpus callosum occasionally occur following
      successful ventricular decompression in patients with chronic hydrocephalus.
      There are certain features on imaging that suggest the diagnosis of what the
      authors propose be termed "postshunting corpus callosum swelling," including
      diffuse high T2 signal predominantly affecting the body of the corpus callosum,
      with transverse orientation along the crossing white matter tracts and scalloping
      along the posterior margin of the structure. In this report, the authors
      demonstrate preservation of the corpus callosum white matter fiber tracts by
      using diffusion tensor imaging with tractography.

PMID- 23157396
TI  - The pars intermedia: an anatomic basis for a coordinated vascular response to
      female genital arousal.
AB  - INTRODUCTION: The pars intermedia is an area of the vulva that has been
      inconsistently described in the literature. AIM: We conducted anatomic studies to
      better describe the tissues and vascular structures of the pars intermedia and
      proposed a functional rationale of the pars intermedia in the female sexual
      response. METHODS: Nine cadaveric vulvectomy specimens were used. Each was
      serially sectioned and stained with hematoxylin and eosin and Masson's trichrome.
      MAIN OUTCOME MEASURES: Histologic ultrastructural description of the pars
      intermedia. RESULTS: The pars intermedia contains veins traveling longitudinally
      in the angle of the clitoris, supported by collagen-rich stromal tissues. These
      veins drain the different vascular compartments of the vulva, including the
      clitoris, the bulbs, and labia minora; also, the interconnecting veins link the
      different vascular compartments. The pars intermedia is not composed of erectile
      tissue, distinguishing it from the erectile tissues of the corpora cavernosa of
      the clitoris as well as the corpus spongiosum of the clitoral (vestibular) bulbs.
      CONCLUSIONS: The venous communications of the pars intermedia, linking the
      erectile tissues with the other vascular compartments of the vulva, appear to
      provide the anatomic basis for a coordinated vascular response during female
      sexual arousal.

PMID- 23157397
TI  - Spatial distribution of transgenic protein after gene electrotransfer to porcine
      muscle.
AB  - Gene electrotransfer is an effective nonviral technique for delivery of plasmid
      DNA into tissues. From a clinical perspective, muscle is an attractive target
      tissue as long-term, high-level transgenic expression can be achieved. Spatial
      distribution of the transgenic protein following gene electrotransfer to muscle
      in a large animal model has not yet been investigated. In this study, 17
      different doses of plasmid DNA (1-1500 MUg firefly luciferase pCMV-Luc) were
      delivered in vivo to porcine gluteal muscle using electroporation. Forty-eight
      hours post treatment several biopsies were obtained from each transfection site
      in order to examine the spatial distribution of the transgenic product. We found
      a significantly higher luciferase activity in biopsies from the center of the
      transfection site compared to biopsies taken adjacent to the center, 1 and 2 cm
      along muscle fiber orientation (p<0.05 and p<0.0001, respectively). On average,
      43% of the total luciferase activity was localized in the center biopsy. In
      conclusion, we found that gene electrotransfer to muscle in a large animal model
      led to localized gene expression corresponding to the area delineated by the
      electrodes. High doses of plasmid DNA did not lead to a larger area of the muscle
      expressing the transgenic protein.

PMID- 23157399
TI  - Chemically modified tandem repeats in proteins: natural combinatorial peptide
      libraries.
AB  - Many proteins composed of tandem repeats (a linear motif, directly repeated
      within the sequence) are substrates for post-translational modifications (PTMs).
      Tandem repeats are also dynamic in number, presumably due to instability in the
      underlying DNA sequence. These observations lead to a hypothesis that cells use a
      combination of PTMs and variability in repeat number to mediate protein function.
      Evidence of these processes co-regulating diverse aspects of cellular function
      can be found in all organisms from bacteria to humans, suggesting a common but
      poorly described mechanism for regulating and diversifying protein function. This
      review highlights several examples whereby protein modifications and repetitive
      protein domains impart diversity. Lastly, it speculates on the possibility of
      using chemically modified repetitive amino acid sequences to develop peptide
      based biomolecules with novel functions.

PMID- 23157398
TI  - Living vs. deceased donor liver transplantation for hepatocellular carcinoma: a
      systematic review and meta-analysis.
AB  - Experimental studies suggest that the regenerating liver provides a "fertile
      field" for the growth of hepatocellular carcinoma (HCC). However, clinical
      studies report conflicting results comparing living donor liver transplantation
      (LDLT) and deceased donor liver transplantation (DDLT) for HCC. Thus, disease
      free survival (DFS) and overall survival (OS) were compared after LDLT and DDLT
      for HCC in a systematic review and meta-analysis. Twelve studies satisfied
      eligibility criteria for DFS, including 633 LDLT and 1232 DDLT. Twelve studies
      satisfied eligibility criteria for OS, including 637 LDLT and 1050 DDLT.
      Altogether, there were 16 unique studies; 1, 2, and 13 of these were rated as
      high, medium, and low quality, respectively. Studies were heterogeneous, non
      randomized, and mostly retrospective. The combined hazard ratio was 1.59 (95%
      confidence interval [CI]: 1.02-2.49; I(2) = 50.07%) for DFS after LDLT vs. DDLT
      for HCC, and 0.97 (95% CI: 0.73-1.27; I(2) = 5.68%) for OS. This analysis
      provides evidence of lower DFS after LDLT compared with DDLT for HCC. Improved
      study design and reporting is required in future research to ascribe the observed
      difference in DFS to study bias or biological risk specifically associated with
      LDLT.

PMID- 23157400
TI  - Sexual violence and HIV transmission: summary proceedings of a scientific
      research planning meeting.

PMID- 23157401
TI  - Cell-specific effects on surface alpha7 nicotinic receptor expression revealed by
      over-expression and knockdown of rat RIC3 protein.
AB  - We tested whether surface alpha7 nicotinic acetylcholine receptor expression is
      dependent on an endogenous chaperone named Resistance to Inhibitors of
      Cholinesterase 3 (RIC3) by comparing RIC3 protein in rat GH4C1 and human SH-EP1
      cells, which express strikingly different surface receptor levels following
      alpha7 transfection. Cloned rat RIC3 exists in at least two isoforms because of
      an ambiguous splice site between exons 4 and 5. Both rat isoforms permit surface
      alpha7 expression in SH-EP1 and human embryonic kidney (HEK) cells measured by
      alpha-bungarotoxin binding. Contrary to expectations, endogenous RIC3 protein
      expression determined by immunoblots did not differ between untransfected GH4C1
      or SH-EP1 cells. siRNA against rat RIC3 exon 4 and shRNA against exons 2, 5 and 6
      knocked down transfected rat RIC3 expression in SH-EP1 cells and simultaneously
      blocked toxin binding. However, no RNAi construct blocked binding when co
      transfected with alpha7 into GH4C1 cells. shRNA against rat exons 2 and 5 knocked
      down rat RIC3 protein transfected into GH4C1 cells with a time course suggesting
      a protein half-life of a few days. These results suggest GH4C1 cells may possess
      unknown chaperone(s) allowing high surface alpha7 expression in the absence of
      known RIC3 splice variants.

PMID- 23157402
TI  - Multicomponent synthesis of diverse 1,4-benzodiazepine scaffolds.
AB  - The 1,4-benzodiazepine (BDZ) scaffold is of particular interest in drug design
      due to a balanced ensemble of beneficial physicochemical properties including a
      semirigid and compact diazepine ring with spatial placements of several
      substituents, combined with low number of rotatable bonds, hydrogen bond donors
      and acceptors, and intermediate lipophilicity. As an alternative to traditional
      multistep sequential syntheses, we designed routes employing one-pot MCRs to
      accelerate access diverse BDZ scaffolds in two or three steps.

PMID- 23157403
TI  - An interpretive phenomenological study of Chinese mothers' experiences of
      constant vigilance in caring for a hospitalized sick child.
AB  - AIM: To examine Chinese mothers' experience of caring for their hospitalized sick
      child. BACKGROUND: Engaging the mother in providing care for a hospitalized sick
      child is considered one of the key elements for high-quality care in advanced
      paediatric nursing. There is evidence that a mother's belief in her capacity to
      manage stressful situations could improve the nurse-parent relationship because
      they might play an important role in protecting mothers against heightened stress
      during crisis situation. DESIGN: An interpretive phenomenological approach
      involving semi-structured interview and thematic analysis was used. METHOD:
      Fifteen interviews were conducted in Hong Kong, China from April 2009-January
      2010, with 15 mothers caring for their hospitalized sick children with acute
      injury or illness. Crist and Tanner's circular process of hermeneutic
      interpretive phenomenology was chosen to guide the data analysis. FINDINGS: The
      prevailing concept identified through analysis was the 'constant vigilance' that
      mothers developed. Interpretation of data resulted in the identification of four
      key themes: 'being sensitive to others', 'providing helping hands', 'monitoring
      health conditions', and 'maintaining dialogues'. The findings highlight Chinese
      mothers' desire for participation in caring for their hospitalized child, their
      unexpressed needs for communication, and concern about being uncared by the busy
      health professionals, which affect their care for the child's health outcomes.
      CONCLUSION: The findings facilitate the development of family-centred care
      focuses on partnership of care between the nurse and family to enhance the
      Chinese family's active and participatory role.

PMID- 23157404
TI  - Catalysis of nickel ferrite for photocatalytic water oxidation using [Ru(bpy)3]2+
      and S2O8(2-).
AB  - Single or mixed oxides of iron and nickel have been examined as catalysts in
      photocatalytic water oxidation using [Ru(bpy)(3)](2+) as a photosensitizer and
      S(2)O(8)(2-) as a sacrificial oxidant. The catalytic activity of nickel ferrite
      (NiFe(2)O(4)) is comparable to that of a catalyst containing Ir, Ru, or Co in
      terms of O(2) yield and O(2) evolution rate under ambient reaction conditions.
      NiFe(2)O(4) also possesses robustness and ferromagnetic properties, which are
      beneficial for easy recovery from the solution after reaction. Water oxidation
      catalysis achieved by a composite of earth-abundant elements will contribute to a
      new approach to the design of catalysts for artificial photosynthesis.

PMID- 23157405
TI  - Extension of Brownian dynamics for studying blockers of ion channels.
AB  - We present new Brownian dynamics techniques for studying blockers of ion
      channels. By treating the channel as a fixed body, simulating the blocker
      molecules using rigid bodies, and using an implicit water force field with
      explicit ions, we are able to carry out fast simulations that can be used to
      investigate the dynamics of block and unblock, deduce binding modes, and
      calculate binding affinities. We test our program using the NavAb bacterial
      sodium channel, whose structure was recently solved (Payandeh et al. Nature,
      2011, 475, 353-358) in conjunction with the MU-conotoxin PIIIA blocker. We derive
      an ohmic current-voltage relationship for channel permeation, calculate
      potentials of mean force for blocker unbinding, and deduce multiple binding modes
      for the blocker. Our results are shown to be compatible with other computational
      and experimental results. Finally, we discuss future improvements such as the
      inclusion of flexible side chains. After these improvements are carried out, we
      anticipate our program will be an extremely useful new tool that could be used to
      help develop new drugs to treat a range of ion-channel related diseases.

PMID- 23157406
TI  - Metabolomics and ischaemic heart disease.
AB  - Ischaemic heart disease accounts for nearly half of the global cardiovascular
      disease burden. Aetiologies relating to heart disease are complex, but
      dyslipidaemia, oxidative stress and inflammation are cardinal features. Despite
      preventative measures and advancements in treatment regimens with lipid-lowering
      agents, the high prevalence of heart disease and the residual risk of recurrent
      events continue to be a significant burden to the health sector and to the
      affected individuals and their families. The development of improved risk models
      for the early detection and prevention of cardiovascular events in addition to
      new therapeutic strategies to address this residual risk are required if we are
      to continue to make inroads into this most prevalent of diseases. Metabolomics
      and lipidomics are modern disciplines that characterize the metabolite and lipid
      complement respectively, of a given system. Their application to ischaemic heart
      disease has demonstrated utilities in population profiling, identification of
      multivariate biomarkers and in monitoring of therapeutic response, as well as in
      basic mechanistic studies. Although advances in magnetic resonance and mass
      spectrometry technologies have given rise to the fields of metabolomics and
      lipidomics, the plethora of data generated presents challenges requiring specific
      statistical and bioinformatics applications, together with appropriate study
      designs. Nonetheless, the predictive and re-classification capacity of
      individuals with various degrees of risk by the plasma lipidome has recently been
      demonstrated. In the present review, we summarize evidence derived exclusively by
      metabolomic and lipidomic studies in the context of ischaemic heart disease. We
      consider the potential role of plasma lipid profiling in assessing heart disease
      risk and therapeutic responses, and explore the potential mechanisms. Finally, we
      highlight where metabolomic studies together with complementary -omic disciplines
      may make further inroads into the understanding, detection and treatment of
      ischaemic heart disease.

PMID- 23157407
TI  - Local bone marrow renin-angiotensin system in primitive, definitive and
      neoplastic haematopoiesis.
AB  - The locally active ligand peptides, mediators, receptors and signalling pathways
      of the haematopoietic BM (bone marrow) autocrine/paracrine RAS (renin-angiotensin
      system) affect the essential steps of definitive blood cell production.
      Haematopoiesis, erythropoiesis, myelopoiesis, formation of monocytic and
      lymphocytic lineages, thrombopoiesis and other stromal cellular elements are
      regulated by the local BM RAS. The local BM RAS is present and active even in
      primitive embryonic haematopoiesis. ACE (angiotensin-converting enzyme) is
      expressed on the surface of the first endothelial and haematopoietic cells,
      forming the marrow cavity in the embryo. ACE marks early haematopoietic precursor
      cells and long-term blood-forming CD34(+) BM cells. The local autocrine tissue BM
      RAS may also be active in neoplastic haematopoiesis. Critical RAS mediators such
      as renin, ACE, AngII (angiotensin II) and angiotensinogen have been identified in
      leukaemic blast cells. The local tissue RAS influences tumour growth and
      metastases in an autocrine and paracrine fashion via the modulation of numerous
      carcinogenic events, such as angiogenesis, apoptosis, cellular proliferation,
      immune responses, cell signalling and extracellular matrix formation. The aim of
      the present review is to outline the known functions of the local BM RAS within
      the context of primitive, definitive and neoplastic haematopoiesis. Targeting the
      actions of local RAS molecules could represent a valuable therapeutic option for
      the management of neoplastic disorders.

PMID- 23157408
TI  - A little winning streak: the reptilian-eye view of gastrulation in birds.
AB  - The primitive streak is where the mesoderm and definitive endoderm precursor
      cells ingress from the epiblast during gastrulation. It is often described as an
      embryological feature common to all amniotes. But such a feature has not been
      associated with gastrulation in any reptilian species. A parsimonious model would
      be that the primitive streak evolved independently in the avian and mammalian
      lineages. Looking beyond the primitive streak, can one find shared features of
      mesoderm and endoderm formation during amniote gastrulation? Here, we survey the
      literature on reptilian gastrulation and provide new data on Brachyury RNA and
      laminin protein expression in gastrula-stage turtle (Pelodiscus sinensis)
      embryos. We propose a model to reconcile the primitive streak-associated
      gastrulation in birds and the blastopore-associated gastrulation in extant
      reptiles.

PMID- 23157409
TI  - The circadian rhythm of arterial blood pressure in Alzheimer disease (AD)
      patients without hypertension.
AB  - OBJECTIVES: The circadian rhythm (CR) of arterial blood pressure (ABP) in
      Alzheimer disease (AD) patients was examined in a case-control clinical study.
      METHODS: This study was constructed using the case-control method and
      investigates non-hypertensive AD patients, compared with normotensive controls
      from a primary care setting. Twenty-four-hour ABP was measured with an automatic
      oscillometric device and recorded every 30 min throughout the day and night.
      Extreme dipper, dipper, non-dipper and reverse-dipper patterns were defined as
      those individuals with > 20%, 10-20%, < 10% and no fall in nocturnal ABP relative
      to daytime values. RESULTS: There were significant differences in ABP dipper
      status between cases and controls (cases - 16.15%, 60.00%, 17.70% and 6.15% vs
      controls - 3.19%, 31.9 2%, 42.02% and 22.88% for reverse dipper, non-dipper,
      dipper and extreme dipper, respectively, df = 3, chi(2) = 56.76, p < 0.001).
      Compared with normal controls, AD patients had significantly higher 24-h mean
      blood pressure, 24-h mean systolic blood pressure (SBP), night mean SBP, night
      mean pulse pressure (PP) and 24-h mean PP. There were no significant differences
      in 24-h mean diastolic blood pressure (DBP), daytime mean DBP or night-time mean
      DBP, and no significant differences in daytime mean SBP. CONCLUSIONS: The
      circadian rhythm of ABP in AD patents differed from normal controls, perhaps from
      higher night SBP in AD patents.

PMID- 23157411
TI  - Fundamentals for LC miniaturization.

PMID- 23157410
TI  - Micrometer scale guidance of mesenchymal stem cells to form structurally oriented
      cartilage extracellular matrix.
AB  - Tissue engineering is a possible method for long-term repair of cartilage
      lesions, but current tissue-engineered cartilage constructs have inferior
      mechanical properties compared to native cartilage. This problem may be due to
      the lack of an oriented structure in the constructs at the microscale that is
      present in the native tissue. In this study, we utilize contact guidance to
      develop constructs with microscale architecture for improved chondrogenesis and
      function. Stable channels of varying microscale dimensions were formed in
      collagen-based and polydimethylsiloxane membranes via a combination of
      microfabrication and soft-lithography. Human mesenchymal stem cells (MSCs) were
      selectively seeded in these channels. The chondrogenic potential of MSCs seeded
      in these channels was investigated by culturing them for 3 weeks under
      differentiating conditions, and then evaluating the subsequent synthesized tissue
      for mechanical function and by type II collagen immunohistochemistry. We
      demonstrate selective seeding of viable MSCs within the channels. MSC aligned and
      produced mature collagen fibrils along the length of the channel in smaller
      linear channels of widths 25-100 MUm compared to larger linear channels of widths
      500-1000 MUm. Further, substrates with microchannels that led to cell alignment
      also led to superior mechanical properties compared to constructs with randomly
      seeded cells or selectively seeded cells in larger channels. The ultimate stress
      and modulus of elasticity of constructs with cells seeded in smaller channels
      increased by as much as fourfolds. We conclude that microscale guidance is useful
      to produce oriented cartilage structures with improved mechanical properties.
      These findings can be used to fabricate large clinically useful MSC-cartilage
      constructs with superior mechanical properties.

PMID- 23157413
TI  - QSAR modeling for the antimalarial activity of 1,4-naphthoquinonyl derivatives as
      potential antimalarial agents.
AB  - Malaria has been known as one of the major causes of morbidity and mortality on a
      large scale in tropical countries until now. In the past decades, many scientific
      groups have focused their attention on looking for ideal drugs to this disease.
      So far, this research area is still a hot topic. In the present study, the
      antimalarial activity of 1, 4- naphthoquinonyl derivatives was modeled by linear
      and nonlinear statistical methods, that is to say, by forward stepwise
      multilinear regression (MLR) and radial basis function neural networks (RBFNN).
      The derived QSAR models have been statistically validated both internally - by
      means of the Leave One Out (LOO) and Leave Many Out (LMO) crossvalidation, and Y
      scrambling techniques, as well as externally (by means of an external test set).
      The statistical parameters provided by the MLR model were R(2) =0.7876, LOOq(2)
      =0.7068, RMS =0.3377, R0 2 =0.7876, k =1.0000 for the training set,and R(2)
      =0.7648, q(2) ext =0.7597, RMS=0.2556, R0 2=0.7598, k=1.0417 for the external
      test set. The RBFNN model gave the following statistical results, namely:
      R(2)=0.8338, LOOq(2)=0.5869, RMS=0.2781, R0 2 = 0.8335, k=1.0000 for the training
      set, and R(2) =0.7586, q(2) ext =0.7189, RMS=0.2788, R0 2=0.7129, k=1.0284 for
      the external test set. Overall, these results suggest that the QSAR MLR-based
      model is a simple, reliable, credible and fast tool for the prediction and
      virtual screening of 1, 4-naphoquinone derivatives with high antimalarial
      activity. In addition, the energies of the highest occupied molecular orbital
      were found to have high correlation with the activity. 

PMID- 23157414
TI  - Quantum mechanical scoring: structural and energetic insights into cyclin
      dependent kinase 2 inhibition by pyrazolo[1,5-a]pyrimidines.
AB  - A quantum mechanics (QM)-based scoring function has been applied to complexes of
      cyclin-dependent kinase 2 (CDK2) and thirty-one pyrazolo[1,5-a]pyrimidine-based
      inhibitors and their bioisosteres. A hybrid three-layer QM/MM setup (DFT-D/PM6
      D3H4X/AMBER in generalized Born solvent) was used here for the first time as an
      extension of our previous full QM and SQM/MM (SQM means semiempirical QM)
      approaches. Two approaches to obtain the structures of the CDK2/inhibitor
      complexes were examined: i) building the modifications from one X-ray structure
      available coupled with a conformational search and ii) docking the compounds into
      CDK2. The QM-based scoring entailed a QM/SQM/MM optimization followed by
      calculations of the binding scores which were subsequently correlated with the
      experimental binding free energies. The correlation for the building protocol was
      good (r(2) = 0.64, predictive index = 0.81), whereas the docking approach failed.
      A decomposition of the interaction energies to ligand fragments enabled us to
      rationalize the differences in the binding affinities. In conclusion, we have
      developed and refined a QM-based scoring protocol and successfully applied it to
      reproduce the binding affinities in congeneric series of CDK2 inhibitors and to
      rationalize their potency. We thus propose that such a tool can be used in
      computer-aided rational drug design. 

PMID- 23157412
TI  - Identification of proteins binding coding and non-coding human RNAs using protein
      microarrays.
AB  - BACKGROUND: The regulation and function of mammalian RNAs has been increasingly
      appreciated to operate via RNA-protein interactions. With the recent discovery of
      thousands of novel human RNA molecules by high-throughput RNA sequencing,
      efficient methods to uncover RNA-protein interactions are urgently required.
      Existing methods to study proteins associated with a given RNA are laborious and
      require substantial amounts of cell-derived starting material. To overcome these
      limitations, we have developed a rapid and large-scale approach to characterize
      binding of in vitro transcribed labeled RNA to ~9,400 human recombinant proteins
      spotted on protein microarrays. RESULTS: We have optimized methodology to probe
      human protein microarrays with full-length RNA molecules and have identified 137
      RNA-protein interactions specific for 10 coding and non-coding RNAs. Those
      proteins showed strong enrichment for common human RNA binding domains such as
      RRM, RBD, as well as K homology and CCCH type zinc finger motifs. Previously
      unknown RNA-protein interactions were discovered using this technique, and these
      interactions were biochemically verified between TP53 mRNA and Staufen1 protein
      as well as between HRAS mRNA and CNBP protein. Functional characterization of the
      interaction between Staufen 1 protein and TP53 mRNA revealed a novel role for
      Staufen 1 in preserving TP53 RNA stability. CONCLUSIONS: Our approach
      demonstrates a scalable methodology, allowing rapid and efficient identification
      of novel human RNA-protein interactions using RNA hybridization to human protein
      microarrays. Biochemical validation of newly identified interactions between TP53
      Stau1 and HRAS-CNBP using reciprocal pull-down experiments, both in vitro and in
      vivo, demonstrates the utility of this approach to study uncharacterized RNA
      protein interactions.

PMID- 23157415
TI  - Suppression of tongue squamous cell carcinoma growth by inhibition of Jagged1 in
      vitro and in vivo.
AB  - BACKGROUND: The changes in Notch signaling are closely related to the occurrence
      and development of many cancers. We have investigated Notch signaling receptor
      and its ligand expressions in TSCC cell lines, tissues and its significance. We
      clarified Notch signaling pathway in TSCC and its mechanism. We regulated Notch
      signaling pathway of tumor cells, thereby inhibiting tumor cell proliferation and
      differentiation. METHODS: We detected Jagged1 protein and mRNA expression levels
      in specimens (tongue cancer and adjacent tissues) from 74 patients with tongue
      cancer and in TSCC cell line. The Jagged1-targeted lentiviral vector RNAi system
      was constructed, and its suppressive effects on the proliferation and invasion of
      tongue carcinoma cells in in vivo and ex vivo were determined. RESULTS: Jagged1
      was expressed in tongue squamous cell cancer tissues and cell line, but there
      were differences in its expression. Jagged1 was knocked down and the tumor growth
      was inhibited accompanying cell cycle changes. Animal studies also showed that
      the tumor growth was inhibited. CONCLUSIONS: Jagged1 may be involved in the
      differentiation and proliferation of tongue cancer. Targeting Jagged1 RNA
      interference lentiviral vector can effectively lower Jagged1 mRNA and protein
      expression levels of Tca8113 cells, thereby preventing the proliferation of TSCC
      cells. Jagged1 is expected to be a promising new target for curing tongue cancer.
      In-depth study of the interaction between Jagged1 and other molecules of Notch
      signaling pathway in the process of carcinogenesis has important theoretical
      guidance and clinical significance in revealing the mechanism of Jagged1 and its
      application in the therapy for tongue cancer.

PMID- 23157416
TI  - Validity of the National Acoustic Laboratories procedure for determining
      percentage loss of hearing.
AB  - OBJECTIVE: To evaluate the validity of the National Acoustic Laboratories
      procedure for determining percentage loss of hearing as a measure of hearing
      disability. DESIGN: The percentage hearing losses of war veterans who had hearing
      ranging from normal to profound deafness were determined and compared with their
      scores on two hearing questionnaires. STUDY SAMPLE: A self-report hearing
      questionnaire was completed by 282 war veterans and 154 of those veterans were
      given the hearing measurement scale in the form of a structured interview.
      RESULTS: A percentage loss of hearing of 0 agreed well with the questionnaire
      scores representing the limit of normal hearing, and a percentage loss of hearing
      of 100 agreed well with the questionnaire scores representing total loss of
      hearing. Percentage loss of hearing accounted for 83% of the variance in scores
      on the hearing questionnaire and 81% of the variance in scores on the hearing
      measurement scale. CONCLUSION: The National Acoustic Laboratories procedure for
      determining percentage loss of hearing provides a valid measure of hearing
      disability.

PMID- 23157417
TI  - Different labour outcomes in primiparous women that have been subjected to
      childhood sexual abuse or rape in adulthood: a case-control study in a clinical
      cohort.
AB  - OBJECTIVE: To compare the duration and outcome of the first labour in women who
      have been subjected to childhood sexual abuse (CSA) and women who have been raped
      in adulthood (RA). DESIGN: Case-control study in a clinical cohort. SETTING:
      University Hospital of North Norway. SAMPLE: In all, 373 primiparas: 185
      subjected to CSA, 47 to RA and 141 controls without a history of abuse. METHODS:
      Data on birth outcomes were retrieved from the patient files. Information on
      sexual abuse was reported in consultation with specialised midwives in the mental
      health team. Birth outcomes were analysed by multinominal regression analysis.
      MAIN OUTCOME MEASURES: Vaginal births, delivery by caesarean section, operative
      vaginal delivery and duration of labour. RESULTS: As compared with controls, the
      RA group showed a significantly higher risk for caesarean section (adjusted OR
      9.9, 95% CI 3.4-29.4) and operative vaginal delivery (adjusted OR 12.2, 95% CI
      4.4-33.7). There were no significant differences between the CSA and the control
      group. The RA group displayed significantly longer duration of labour in all
      phases as compared with the control and CSA groups. CONCLUSIONS: There were major
      differences in the duration of labour and birth outcomes in the two abuse groups.
      Despite a higher proportion of obstetric risk factors at onset of labour in the
      CSA group, women subjected to CSA had shorter labours and less risk for caesarean
      section and operative vaginal deliveries than women subjected to RA. The best
      care for birthing women subjected to sexual abuse needs to be explored in further
      studies.

PMID- 23157418
TI  - Binding selectivity studies of phosphoinositide 3-kinases using free energy
      calculations.
AB  - Phosphoinositide 3-kinases (PI3Ks) and their phosphatidylinositol 3,4,5
      triphosphate (PIP(3)) products regulate a variety of cellular processes. Of
      these, PI3Kalpha is an attractive target for anticancer drug design. Mutations in
      the PI3Kalpha kinase domain alter the mobility of the activation loop resulting
      in gain of function. We employed molecular dynamics (MD) simulations-based
      energetic analysis using molecular mechanics/generalized born surface area
      (MM/GBSA) for PI3Kalpha and -gamma. MD simulations were carried out for PI3K
      models based on the RESP (restrained electrostatic potential) and quantum
      mechanics (QM)-polarized ligand docking (QPLD)-derived partial charges.
      Computational alanine scanning was also used to evaluate the contributions of key
      binding residues to ligand binding. Our results show that both RESP and QPLD
      charge models of PI3Kalpha and PI3Kgamma provide similar performance in MD
      simulations.  For example, the predicted RESP and QPLD free energies of -9.5 and 
      9.3 kcal/mol for LY294002 binding to PI3Kgamma and -10.9 and -11.7 kcal/mol for
      wortmannin binding to PI3Kalpha are in good agreement with experimental values. A
      significant loss in binding free energy was observed when hydrophobic residues
      were mutated to alanine, suggesting that specific hydrophobic interactions are
      important to optimal ligand binding. MM/GBSA calculations suggested that residues
      Ser774, Gln859, and Ile932 of PI3Kalpha might be used to design H1047R mutant
      specific ligands, whereas Lys890 of PI3Kgamma can be used for ligand design
      targeting PI3Kgamma.

PMID- 23157419
TI  - Protein-polyanion interactions for the controlled release of monoclonal
      antibodies.
AB  - The objective of the present study was to investigate ionic interactions between
      alginate and a monoclonal antibody (mAb1) and to utilize those interactions for
      the sustained release of mAb1. The existence of ionic interactions between
      alginate and mAb1 was strongly reflected by their rheological behavior. A 3-4
      times increase in storage modulus (G') was observed by addition of 30 mg/mL mAb1
      to a 20 mg/mL alginate solution. This increase was strongly dependent on pH and
      ionic strength. In vitro release studies revealed a marked pH-dependence of
      release rates and the reversibility of alginate-mAb1 complexation under
      physiological conditions. Two alginate-mAb1 sustained release formulations were
      developed by an internal gelation technique using CaCO(3) and CaHPO(4) as calcium
      sources for physical cross-linking. The CaCO(3) formulation provided a stable pH
      environment, optimally suited for pH-sensitive proteins. CaHPO(4) led to a lower
      pH and stronger alginate-mAb1 interactions. The CaHPO(4) cross-linked alginate
      released mAb1 over a period of 10-15 days. The long release period and changes in
      viscoelastic properties of alginate, when being mixed with mAb1, indicate the
      incorporation of mAb1 molecules into a mixed network with alginate. The results
      of this study demonstrate that ionic interactions between polyanions and mAb1 are
      present and that they can be exploited for sustained release delivery of mAb1.

PMID- 23157420
TI  - Divergent synthesis of cytotoxic styryl lactones related to goniobutenolides A
      and B, and to crassalactone D.
AB  - Goniobutenolides A (1) and B (2), crassalactone D (3), 4-epi-crassalactone D (4),
      and the corresponding 7-epimers have been synthesized starting from d-glucose.
      The key step in the synthesis of 1 and 2 is a new one-pot sequence comprised of a
      Z-selective Wittig olefination/lactonization/beta-elimination. Preparation of 3
      and 4 included the final 5-endo-trig spirocyclization of 1 and 2. The synthesized
      products were evaluated for their in vitro antiproliferative activity against
      selected tumor cell lines.

PMID- 23157421
TI  - New-onset diabetes mellitus following pediatric liver transplantation.

PMID- 23157422
TI  - TGF-beta1, Smad-2/-3, Smad-1/-5/-8, and Smad-4 signaling factors are expressed in
      ameloblastomas, adenomatoid odontogenic tumors, and calcifying cystic odontogenic
      tumors: an immunohistochemical study.
AB  - OBJECTIVES: The TGF-beta/Smad signaling pathway regulates diverse cellular
      functions, including tooth development, and is involved in numerous pathological
      processes such as tumorigenesis. The aim of this study was to investigate the
      immunoexpression of the TGF-beta/Smad signaling pathway members in ameloblastoma
      (AM), calcifying cystic odontogenic tumor (CCOT), and adenomatoid odontogenic
      tumor (AOT). MATERIALS AND METHODS: This retrospective cross-sectional study
      included 65 tissue specimens: 34 AMs, 13 CCOTs, and 18 AOTs. Serial sections were
      immunohistochemically stained with TGF-beta1, Smad-4, Smad-1/-5/-8, and Smad-2/-3
      antibodies, and a semiquantitative measurement of the positive cells was carried
      out by two oral pathologists using a 0-3 scale (0: no immunoreactivity, 1: <20%
      positive cells, 2: 20-50% positive cells, 3: >50% positive cells). RESULTS: All
      biomarkers studied were found significantly decreased in AM compared to CCOT and
      AOT. AOT and CCOT expressed Smad-1/-5/-8 more strongly compared to AM (OR =
      11.66, P < 0.001 and OR = 5.34, P = 0.013, respectively), and Smad-2/-3
      immunostaining was found significantly increased in CCOT (OR = 10.42, P = 0.001)
      and AOT (OR = 5.16, P < 0.004) compared to AM. Similarly, Smad-4 was expressed
      more strongly in AOT and CCOT compared to AM (P = 0.001), while AOT demonstrated
      a fivefold higher chance to express TGF-beta1 compared to AM (P = 0.011).
      CONCLUSION: TGF-beta/Smad signaling pathway is activated in AM, AOT, and CCOT.
      The statistically significant reduced TGF-beta1/Smad immunoexpression in AM
      compared to AOT/CCOT could be associated with the more aggressive biological
      behavior of AM including increased cell proliferation and reduced apoptosis and
      differentiation. Thus, the biomarkers TGF-beta, Smad-4, Smad-1/-5/-8, and Smad-2/
      3 could serve as supplementary diagnostic indices between odontogenic tumors of
      high and low neoplastic dynamics.

PMID- 23157424
TI  - Genital immunology and HIV susceptibility in young women.
AB  - Women account for a substantial majority of HIV infections in endemic regions,
      where women are also infected at a much younger age than men. Part of this
      epidemiological skewing is due to socio-cultural factors, but it is clear that
      biological factors enhance the susceptibility of women--particularly young women-
      to HIV acquisition after sexual exposure. These factors, including important
      differences in mucosal immunology at the site of genital HIV exposure, are the
      focus of this concise review. Compared to heterosexual men, women have an
      increased surface area of mucosal HIV exposure, increased mucosal expression of
      the HIV co-receptor CCR5 and a greater probability of virus exposure on the
      rectal mucosa. Differences that are specific to young women include a pro
      inflammatory immune environment and a proportionate increase in single-cell,
      columnar genital epithelium. These important biological reasons for enhanced HIV
      susceptibility in young women highlight the need for targeted HIV prevention
      within this vulnerable population.

PMID- 23157423
TI  - Induction of re-differentiation of passaged rat chondrocytes using a naturally
      obtained extracellular matrix microenvironment.
AB  - Dedifferentiated human chondrocytes severely limit successful hyaline cartilage
      repair in clinical practice. The primary interest of this study is to evaluate
      the naturally obtained cell-derived matrix (CDM) as a physical microenvironment
      for chondrocyte re-differentiation. Once different cell types were cultured for 6
      days and decellularized using detergents and enzymes, the fibroblast-derived
      matrix (FDM), preosteoblast-derived matrix (PDM), and chondrocyte-derived matrix
      (CHDM) were obtained. From scanning electron microscope observation, each CDM was
      found to resemble a fibrous mesh with self-assembled fibrils. Both the FDM and
      PDM showed a more compact matrix structure compared to the CHDM. For
      compositional analysis, sodium dodecyl sulfate-polyacrylamide gel electrophoresis
      displayed numerous matrix proteins, which were quite different from each CDM in
      quantity and type. Specific matrix components, such as fibronectin, type I
      collagen (Col I), and laminin, were detected using immunofluorescent staining. In
      addition, the water contact angle suggests that the FDM is more hydrophilic than
      the PDM or CHDM. The proliferation of rat primary chondrocytes growing on CDMs
      was better than those growing on a plastic coverslip (control) or gelatin.
      Meanwhile, synthesis of glycosaminoglycan (GAG) was more effective for passaged
      chondrocytes (P4) cultivated on CDMs, and the difference was significant compared
      to cells grown on the control or on gelatin. As for the gene expression of
      cartilage-specific markers, CDMs exhibited good chondrocyte re-differentiation
      with time: the dedifferentiating marker, Col I was restrained, whereas the ratio
      between Col II and Col I, and between aggrecan and Col I, as an indicator of re
      differentiation, was greatly improved. In addition, immunofluorescence of Col II
      showed a very positive signal in chondrocytes cultivated for 2 weeks on the CDMs.
      In an additional study, when three-dimensional cell pellets made from either
      plate-grown or matrix-grown dedifferentiated chondrocytes (P5) were cultured for
      4 weeks, the results of Safranin-O staining, immunohistochemistry of Col II, and
      total GAG assay suggested that matrix-grown cells were significantly better in
      the induction of chondrocyte re-differentiation, than those grown on the plate.
      This work suggests that the naturally occurring matrix, CDM, can provide a
      favorable surface texture for cell attachment, proliferation, and more
      importantly, a chondroinductive microenvironment for the re-differentiation of
      dedifferentiated chondrocytes.

PMID- 23157425
TI  - Hydroxamic acids in asymmetric synthesis.
AB  - Metal-catalyzed stereoselective reactions are a central theme in organic
      chemistry research. In these reactions, the stereoselection is achieved
      predominantly by introducing chiral ligands at the metal catalyst's center. For
      decades, researchers have sought better chiral ligands for asymmetric catalysis
      and have made great progress. Nevertheless, to achieve optimal stereoselectivity
      and to catalyze new reactions, new chiral ligands are needed.  Because of their
      high metal affinity, hydroxamic acids play major roles across a broad spectrum of
      fields from biochemistry to metal extraction. Dr. K. Barry Sharpless first
      revealed their potential as chiral ligands for asymmetric synthesis in 1977: He
      published the chiral vanadium-hydroxamic-acid-catalyzed, enantioselective
      epoxidation of allylic alcohols before his discovery of Sharpless asymmetric
      epoxidation, which uses the titanium-tartrate complex as the chiral reagent.
      However, researchers have reported few highly enantioselective reactions using
      metal-hydroxamic acid as catalysts since then.  This Account summarizes our
      research on metal-catalyzed asymmetric epoxidation using hydroxamic acids as
      chiral ligands. We designed and synthesized a series of new hydroxamic acids,
      most notably the C2-symmetric bis-hydroxamic acid (BHA) family. V-BHA-catalyzed
      epoxidation of allylic and homoallylic alcohols achieved higher activity and
      stereoselectivity than Sharpless asymmetric epoxidation in many cases. Changing
      the metal species led to a series of unprecedented asymmetric epoxidation
      reactions, such as (i) single olefins and sulfides with Mo-BHA, (ii) homoallylic
      and bishomoallylic alcohols with Zr- and Hf-BHA, and (iii) N-alkenyl sulfonamides
      and N-sulfonyl imines with Hf-BHA. These reactions produce uniquely
      functionalized chiral epoxides with good yields and enantioselectivities.

PMID- 23157426
TI  - Introduction of functionalized mesopores to metal-organic frameworks via metal
      ligand-fragment coassembly.
AB  - Introduction of functionalized mesopores into microporous metal-organic
      frameworks (MOFs) can endow them with suitable properties for applications in gas
      storage, separation, catalysis, and drug delivery. However, common methods for
      functionalization (including pre- and post-synthetic modifications) of the
      internal surface of a MOF reduce the pore size of the MOF because the additional
      functional groups fill up the pores. We present a metal-ligand-fragment
      coassembly strategy for the introduction of (meso)pores functionalized with
      various substituent groups on the ligand fragments. Astonishingly, this new
      functionalization strategy increases the pore volume of a MOF instead of reducing
      it. Since the ligand fragments are often readily available or easily prepared,
      the new procedure for synthesis of the modified MOFs becomes much easier and more
      applicable than existing approaches. Remarkably, mesopores can be generated
      conveniently and controllably by the coassembly of a ligand and its fragment
      containing the desired functional groups. The fragment/ligand ratio has been
      optimized to preserve the parent structure and to promote maximum mesopore
      introduction, which has led to a systematic evaluation of the effectiveness of a
      series of functional groups for the adsorption of guest molecules.

PMID- 23157427
TI  - Experimental evidence for sildenafil's action in the central nervous system:
      dopamine and serotonin changes in the medial preoptic area and nucleus accumbens
      during sexual arousal.
AB  - INTRODUCTION: Sildenafil is the first effective oral treatment for male erectile
      dysfunction. Although it is generally accepted that its action is peripheral, it
      has been suggested that it influences central neural pathways that are involved
      in male sexual arousal. Recently, it was shown that local sildenafil
      administration enhances extracellular dopamine (DA) in the nucleus accumbens
      (NAcc). AIM: The aim of this study was to determine whether sildenafil
      administration alters dopaminergic and serotonergic activity in the NAcc and the
      medial preoptic area (mPOA) during a model of sexual arousal. METHODS: An acute
      (2 days) or chronic (21 days) sildenafil regimen (1 mg/kg) was administered
      intraperitoneally to male rats. Thirty minutes after the last sildenafil
      injection, all males were exposed to noncontact erection sessions by the
      presentation of inaccessible estrous females. Half of the males had previous
      experience of noncontact sexual encounter and the other half were exposed for the
      first time. MAIN OUTCOME MEASURES: Tissue levels of DA and its metabolites, 3,4
      Dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), as well as
      serotonin (5-HT) and its metabolite 5-HIAA, were measured in the mPOA and NAcc
      with high-performance liquid chromatography with electrochemical detector.
      Dopamine ([DOPAC+HVA]/DA) and serotonin (5-HIAA/5-HT) turnovers were also
      calculated as indices of neurotransmission. RESULTS: In nontrained males, acute
      and chronic sildenafil treatment increased DA and 5-HT turnover rates in the mPOA
      and NAcc. In trained rats, acute sildenafil also increased DA and 5-HT turnover
      rates in both structures, whereas chronic treatment enhanced 5-HT turnover rate
      only in the mPOA and DA turnover rate only in the NAcc. CONCLUSIONS: Our data
      confirm that sildenafil enhances dopaminergic activity in the NAcc, extend these
      findings to the mPOA and furthermore, reveal sildenafil-induced effects on
      serotonergic activity in these brain regions as well. Therefore, present findings
      support an effect of sildenafil on central neural pathways that are involved in
      the control of sexual arousal.

PMID- 23157428
TI  - Impaired induction of long-term potentiation-like plasticity in patients with
      high-functioning autism and Asperger syndrome.
AB  - AIM: We aimed to investigate the induction of long-term potentiation (LTP)-like
      plasticity by paired associative stimulation (PAS) in patients with high
      functioning autism and Asperger syndrome (HFA/AS). METHOD: PAS with an
      interstimulus interval between electrical and transcranial magnetic stimulation
      of 25 ms (PAS(25)) was performed in patients with HFA/AS (n=9; eight males, one
      female; mean age 17 y 11 mo, SD 4 y 5 mo) and in typically developing age-matched
      volunteers (n=9; five males, four females; mean age 22 y 4 mo, SD 5 y 2 mo). The
      amplitude of motor-evoked potentials was measured before PAS(25), immediately
      after stimulation, and 30 minutes and 60 minutes later. A PAS protocol adapted to
      individual N20 latency (PAS(N20+2)) was performed in six additional patients with
      HFA/AS. Short-interval intracortical inhibition was measured using paired-pulse
      stimulation. RESULTS: In contrast to the typically developing participants, the
      patients with HFA/AS did not show a significant increase in motor-evoked
      potentials after PAS(25). This finding could also be demonstrated after
      adaptation for N20 latency. Short-interval intracortical inhibition of patients
      with HFA/AS was normal compared with the comparison group and did not correlate
      with PAS effect. INTERPRETATION: Our results show a significant impairment of LTP
      like plasticity induced by PAS in individuals with HFA/AS compared with typically
      developing participants. This finding is in accordance with results from animal
      studies as well as human studies. Impaired LTP-like plasticity in patients with
      HFA/AS points towards reduced excitatory synaptic connectivity and deficits in
      sensory-motor integration in these patients.

PMID- 23157429
TI  - Hazardous alcohol-drinking problems among a Chinese hospital patient population.
AB  - AIM: The aims of this study were to explore: (1) the prevalence and predictors
      for hazardous alcohol-drinking problems; and (2) previous assessments and
      interventions for alcohol-drinking problems in hospitalized Chinese patients.
      BACKGROUND: Alcohol is legally accessible and widely used in Taiwan, but few
      studies have addressed alcohol-drinking problems in hospital settings. DESIGN: A
      cross-sectional design was used. METHOD: Self-report data were collected in 2009
      from 484 patients at five randomly selected general teaching hospitals. FINDINGS:
      The prevalence of hazardous alcohol-drinking problems was 19.2%. Logistic
      regression analysis revealed that predictors for hazardous drinking problems were
      being male, smoking, and chewing betel quid. Only 29.1% of participants had been
      assessed for drinking problems in the past year. Only 38.7% of participants with
      drinking problems had received a drinking intervention in the past year.
      CONCLUSION: These findings suggest that alcohol problems in Taiwanese general
      teaching hospitals are insufficiently assessed and targeted with interventions.
      Targeting high-risk groups in general teaching hospitals is important to prevent
      patients' drinking problems.

PMID- 23157430
TI  - Intra-arterial bone marrow mononuclear cell distribution in experimental global
      brain ischaemia.
AB  - OBJECTIVES: Bone marrow mononuclear cells (BM-MNCs) can ameliorate focal
      ischaemic brain injury. A global ischaemic brain injury, which can occur after
      cardiac or thoracic surgery, could be an essential target for BM-MNCs. No studies
      using BM-MNCs for this indication have been conducted. DESIGN: Ten porcine
      underwent a global normothermic ischaemic insult, followed by an intra-arterial
      injection of Technetium(99m)-HMPAO-labelled BM-MNCs after 2, 4, 6, 12 or 24
      hours. A whole-body scan and a SPECT/CT were performed 2 hours after the
      injection. Severity of the injury was assessed with EEG and tissue biopsies were
      analysed by scintigraphy. RESULTS: The majority of the cells appeared in the
      lungs and the liver. Only a minimal number of cells were located in the brain.
      Median distribution of cells between organs in all animals was as follows: lungs
      32.7% (30.6-38.2), liver 14.2% (12.0-17.2), spleen 7.3% (3.3-11.3) and kidneys
      2.5% (2.0-3.3). The transplanted cells could not be detected within the brain
      tissue by radionuclide imaging. CONCLUSIONS: Intra-arterially transplanted BM
      MNCs did not migrate to the damaged brain tissue in significant quantity when
      transplanted during the first 24 hours after the global ischaemic insult,
      contrary to results with models of focal brain injury.

PMID- 23157431
TI  - Validity of the Virtual Reality Stroop Task (VRST) in active duty military.
AB  - Virtual environments provide the ability to systematically deliver test stimuli
      in simulated contexts relevant to real world behavior. The current study
      evaluated the validity of the Virtual Reality Stroop Task (VRST), which presents
      test stimuli during a virtual reality military convoy with simulated combat
      threats. Active duty Army personnel (N = 49) took the VRST, a customized version
      of the Automated Neuropsychological Assessment Metrics (ANAM)-Fourth Edition TBI
      Battery (2007) that included the addition of the ANAM Stroop and Tower tests, and
      traditional neuropsychological measures, including the Delis-Kaplan Executive
      Function System version of the Color-Word Interference Test. Preliminary
      convergent and discriminant validity was established, and performance on the VRST
      was significantly associated with computerized and traditional tests of attention
      and executive functioning. Valid virtual reality cognitive assessments open new
      lines of inquiry into the impact of environmental stimuli on performance and
      offer promise for the future of neuropsychological assessments used with military
      personnel.

PMID- 23157432
TI  - The folding of acetyl(Ala)28NH2 and acetyl(Ala)40NH2 extended strand peptides
      into antiparallel beta-sheets. A density functional theory study of beta-sheets
      with beta-turns.
AB  - We report ONIOM calculations using B3LYP/D95** and AM1 on beta-sheet formation
      from acetyl(Ala)(N)NH(2) (N = 28 or 40). The sheets contain from one to four beta
      turns for N = 28 and up to six for N = 40. We have obtained four types of
      geometrically optimized structures. All contain only beta-turns. They differ from
      each other in the types of beta-turns formed. The unsolvated sheets containing
      two turns are most stable. Aqueous solvation (using the SM5.2 and CPCM methods)
      reduces the stabilities of the folded structures compared to the extended
      strands.

PMID- 23157433
TI  - Assessing the community clinic replacement effect on private Medicaid practices
      in oral health care within rural environments.
AB  - OBJECTIVES: Children in Medicaid/CHIP public coverage programs who reside in
      rural counties have limited access to dental care services. Shortages of dental
      professionals in rural areas impede utilization of dental care. Public and
      private initiatives are attempting to address this crisis. Missourians instituted
      deregulatory policies and invested in community-based initiatives. METHODS: Using
      a Medicaid/CHIP claims administrative dataset from 2004 to 2007, this research
      explored patterns of utilization to assess the impact of these efforts. RESULTS:
      The number of participating private dental office providers declined over the
      study period, and the number of children utilizing clinics increased. Trends are
      being observed within the public health dental care market demonstrating clinics
      are replacing private dentists as providers of Medicaid/CHIP dental services.
      CONCLUSIONS: Allowing greater market entry through deregulation could provide
      states with greater improvements to their public dental health infrastructure.

PMID- 23157434
TI  - Characterization and pharmacokinetic evaluation of gamma sterilized ketorolac
      tromethamine loaded albumin microspheres for intramuscular administration.
AB  - Pharmacokinetic parameters of ketorolac tromethamine (KT) loaded albumin (KTAL)
      microspheres were determined using New Zealand white rabbits. Each rabbit (n=6)
      was injected 5 mg/kg body weight of plain KT or an equivalent dose in microsphere
      form in 2 mL water for injection. Prior to animal studies microspheres were
      tested for toxic residues and were gamma sterilized. Sterilized microspheres were
      evaluated for their integrity by physico-chemical characterization. Test for
      toxic residues was negative, the sterilization process utilized was effective and
      did not alter any physicochemical characteristics and showed good syringeability.
      When KT was administered in the form of microspheres there was a significant
      increase in Cmax, AUC, t1/2 and MRT (P < 0.05). When administered as
      microspheres, plasma concentration of drug sustained for 24 hours. It was
      concluded that KTAL microsphere formulation improved the systemic exposure and
      sustained the drug release and could be used for once-a-day administration of KT.

PMID- 23157435
TI  - Immunogenic cell death in cancer therapy.
AB  - Depending on the initiating stimulus, cancer cell death can be immunogenic or
      nonimmunogenic. Immunogenic cell death (ICD) involves changes in the composition
      of the cell surface as well as the release of soluble mediators, occurring in a
      defined temporal sequence. Such signals operate on a series of receptors
      expressed by dendritic cells to stimulate the presentation of tumor antigens to T
      cells. We postulate that ICD constitutes a prominent pathway for the activation
      of the immune system against cancer, which in turn determines the long-term
      success of anticancer therapies. Hence, suboptimal regimens (failing to induce
      ICD), selective alterations in cancer cells (preventing the emission of
      immunogenic signals during ICD), or defects in immune effectors (abolishing the
      perception of ICD by the immune system) can all contribute to therapeutic
      failure. We surmise that ICD and its subversion by pathogens also play major
      roles in antiviral immune responses.

PMID- 23157436
TI  - Drug side-effect prediction based on the integration of chemical and biological
      spaces.
AB  - Drug side-effects, or adverse drug reactions, have become a major public health
      concern and remain one of the main causes of drug failure and of drug withdrawal
      once they have reached the market. Therefore, the identification of potential
      severe side-effects is a challenging issue. In this paper, we develop a new
      method to predict potential side-effect profiles of drug candidate molecules
      based on their chemical structures and target protein information on a large
      scale. We propose several extensions of kernel regression model for multiple
      responses to deal with heterogeneous data sources. The originality lies in the
      integration of the chemical space of drug chemical structures and the biological
      space of drug target proteins in a unified framework. As a result, we demonstrate
      the usefulness of the proposed method on the simultaneous prediction of 969 side
      effects for approved drugs from their chemical substructure and target protein
      profiles and show that the prediction accuracy consistently improves owing to the
      proposed regression model and integration of chemical and biological information.
      We also conduct a comprehensive side-effect prediction for uncharacterized drug
      molecules stored in DrugBank and confirm interesting predictions using
      independent information sources. The proposed method is expected to be useful at
      many stages of the drug development process.

PMID- 23157437
TI  - Maternal mortality in Sweden 1988-2007: more deaths than officially reported.
AB  - OBJECTIVE: To obtain more accurate calculations of maternal and pregnancy-related
      mortality ratios in Sweden from 1988 to 2007 by using information from national
      registers and death certificates. DESIGN: A national register-based study,
      supplemented by a review of death certificates. SETTING: Sweden, 1988-2007.
      POPULATION: The deaths of 27 957 women of reproductive age (15-49 years).
      METHODS: The Swedish Cause of Death Register, Medical Birth Register, and
      National Patient Register were linked. All women with a diagnosis related to
      pregnancy in at least one of these registers within 1 year prior to death were
      identified. Death certificates were reviewed to ascertain maternal deaths.
      Maternal mortality ratio (the number of maternal deaths/100 000 live births,
      excluding and including suicides), and pregnancy-related mortality ratio (number
      of deaths within 42 days after termination of pregnancy, irrespective of cause of
      death/100 000 live births) were calculated. MAIN OUTCOME MEASURES: Direct and
      indirect maternal deaths and pregnancy-related deaths. RESULTS: The maternal
      mortality ratio in Sweden, based on the current method of identifying maternal
      deaths, was 3.6. After linking registers and reviewing death certificates, we
      identified 64% more maternal deaths, resulting in a ratio of 6.0 (or 6.5 if
      suicides are included). The pregnancy-related mortality ratio was 7.3. A total of
      478 women died within a year after being recorded with a diagnosis related to
      pregnancy. CONCLUSIONS: By including the 123 cases of maternal death identified
      in this study, the mean maternal mortality ratio from 1988 to 2007 was 64% higher
      than reported to the World Health Organization.

PMID- 23157438
TI  - Active learning for convenient annotation and classification of secondary ion
      mass spectrometry images.
AB  - Digital staining for the automated annotation of mass spectrometry imaging (MSI)
      data has previously been achieved using state-of-the-art classifiers such as
      random forests or support vector machines (SVMs). However, the training of such
      classifiers requires an expert to label exemplary data in advance. This process
      is time-consuming and hence costly, especially if the tissue is heterogeneous. In
      theory, it may be sufficient to only label a few highly representative pixels of
      an MS image, but it is not known a priori which pixels to select. This motivates
      active learning strategies in which the algorithm itself queries the expert by
      automatically suggesting promising candidate pixels of an MS image for labeling.
      Given a suitable querying strategy, the number of required training labels can be
      significantly reduced while maintaining classification accuracy. In this work, we
      propose active learning for convenient annotation of MSI data. We generalize a
      recently proposed active learning method to the multiclass case and combine it
      with the random forest classifier. Its superior performance over random sampling
      is demonstrated on secondary ion mass spectrometry data, making it an interesting
      approach for the classification of MS images.

PMID- 23157439
TI  - Dynamics of domain coverage of the protein sequence universe.
AB  - BACKGROUND: The currently known protein sequence space consists of millions of
      sequences in public databases and is rapidly expanding. Assigning sequences to
      families leads to a better understanding of protein function and the nature of
      the protein universe. However, a large portion of the current protein space
      remains unassigned and is referred to as its "dark matter". RESULTS: Here we
      suggest that true size of "dark matter" is much larger than stated by current
      definitions. We propose an approach to reducing the size of "dark matter" by
      identifying and subtracting regions in protein sequences that are not likely to
      contain any domain. CONCLUSIONS: Recent improvements in computational domain
      modeling result in a decrease, albeit slowly, in the relative size of "dark
      matter"; however, its absolute size increases substantially with the growth of
      sequence data.

PMID- 23157440
TI  - A general method for the enantioselective synthesis of alpha-chiral heterocycles.
AB  - The enantioselective formation of stereocenters proximal to unprotected
      heterocycles has been accomplished. Thus, vinyl boronic acids are added to
      heterocycle-appended enones via a modified-BINOL catalyst. Catalyst design was
      key to enable a general reaction. High yields and useful er's are observed for a
      host of common heteroaryls.

PMID- 23157441
TI  - Interrelationship of clinical, histomorphometric and immunohistochemical features
      of oral lesions in chronic paracoccidioidomycosis.
AB  - BACKGROUND: This study aimed to analyze the oral lesions of chronic
      paracoccidioidomycosis concerning their histomorphometric, immunohistochemical,
      and clinical features in a standardized sample. METHODS: Fifty biopsy specimens
      of oral lesions of chronic paracoccidioidomycosis were submitted to hematoxylin
      and eosin (H&E), Grocott-Gomori and immunohistochemical staining. Data regarding
      disease duration and size and number of oral lesions, as well as erythrocytes,
      leukocytes, lymphocytes, hematocrit, hemoglobin, and erythrocyte sedimentation
      rate, were collected from medical charts. Granuloma density and number and
      diameter of buds and fungal cells, and IL-2, TNF-alpha and IFN-gamma expression,
      as well as clinical and hematological features, were quantified and correlated.
      RESULTS: Bud diameter was significantly greater in intermediate density
      granulomas compared to higher density granulomas. The other variables (number of
      buds, number and diameter of fungi, expression of IL-2, TNF-alpha and IFN-gamma,
      and clinical and hematological features) did not significantly change with the
      density of granulomas. There was a positive correlation between bud number and
      fungal cell number (r = 0.834), bud diameter and fungal cell diameter (r =
      0.496), erythrocytes and number of fungi (r = 0.420), erythrocytes and bud number
      (r = 0.408), and leukocytes and bud number (r = 0.396). Negative correlation
      occurred between number and diameter of fungi (r = -0.419), bud diameter and
      granuloma density (r = -0.367), TNF-alpha expression and number of fungi (r = 
      0.372), and TNF-alpha expression and bud number (r = -0.300). CONCLUSION: The
      histological, immunological, and clinical features of oral lesions evaluated did
      not differ significantly between patients in our sample of chronic
      paracoccidioidomycosis. TNF-alpha levels were inversely correlated with intensity
      of infection.

PMID- 23157442
TI  - Micro/nanostructured hyaluronic acid matrices with tuned swelling and drug
      release properties.
AB  - Hyaluronic acid (HA) hydrogels were structured in the form of porous monoliths by
      means of the ice-segregation-induced self-assembly (ISISA) method coupled with
      freeze-drying. Physical and chemical parameters were explored in order to fine
      tune the microstructure and the incidence on both swelling and dissolution
      behavior in aqueous media. Gentamicin-loaded HA matrices with tuned drug release
      properties were also prepared; their inherent properties and behavior in solution
      are discussed in the framework of thermal analysis and scanning electron
      microscopy inspection.

PMID- 23157443
TI  - Comment on: Adipokines, hormonal parameters, and cardiovascular risk factors:
      similarities and differences between patients with erectile dysfunction of
      arteriogenic and nonarteriogenic origin.

PMID- 23157444
TI  - Conformational locking by design: relating strain energy with luminescence and
      stability in rigid metal-organic frameworks.
AB  - Minimization of the torsional barrier for phenyl ring flipping in a metal-organic
      framework (MOF) based on the new ethynyl-extended octacarboxylate ligand
      H(8)TDPEPE leads to a fluorescent material with a near-dark state. Immobilization
      of the ligand in the rigid structure also unexpectedly causes significant strain.
      We used DFT calculations to estimate the ligand strain energies in our and all
      other topologically related materials and correlated these with empirical
      structural descriptors to derive general rules for trapping molecules in high
      energy conformations within MOFs. These studies portend possible applications of
      MOFs for studying fundamental concepts related to conformational locking and its
      effects on molecular reactivity and chromophore photophysics.

PMID- 23157445
TI  - Emotional contagion and trait empathy in prosocial behavior in young people: the
      contribution of autonomic (facial feedback) and balanced emotional empathy scale
      (BEES) measures.
AB  - The present research investigated first the facial feedback measured by EMG
      (electromyography) during decisions to engage in prosocial-helping behaviors and
      secondly the relation between this psychophysiological correlate and emotional
      empathy trait in young people. Thirty young subjects were invited to choose to
      adopt or not a prosocial behavior in response to social interactions. An
      increased zygomatic and corrugator muscle activity was found in response to
      prosocial interventions. Moreover, a significant positive correlation was found
      between empathic profile and the EMG modulation. These results highlight the role
      of emotions and empathy in prosocial behavior, induced by an "emotional contagion
      effect."

PMID- 23157446
TI  - Protein tyrosine nitration: biochemical mechanisms and structural basis of
      functional effects.
AB  - In proteins, the nitration of tyrosine residues to 3-nitro-tyrosine represents an
      oxidative post-translational modification that disrupts nitric oxide ((*)NO)
      signaling and skews metabolism towards pro-oxidant processes. Indeed, excess
      levels of reactive oxygen species in the presence of (*)NO or (*)NO-derived
      metabolites lead to the formation of nitrating species such as peroxynitrite.
      Thus, protein 3-nitrotyrosine has been established as a biomarker of cell,
      tissue, and systemic "nitroxidative stress". Moreover, tyrosine nitration
      modifies key properties of the amino acid: phenol group pK(a), redox potential,
      hydrophobicity, and volume. Thus, the incorporation of a nitro group (-NO(2))
      into protein tyrosines can lead to profound structural and functional changes,
      some of which contribute to altered cell and tissue homeostasis.  In this
      Account, I describe our current efforts to define (1) biologically-relevant
      mechanisms of protein tyrosine nitration and (2) how this modification can cause
      changes in protein structure and function at the molecular level. First, I
      underscore the relevance of protein tyrosine nitration via free-radical-mediated
      reactions (in both peroxynitrite-dependent and -independent pathways) involving a
      tyrosyl radical intermediate (Tyr(*)). This feature of the nitration process is
      critical because Tyr(*) can follow various fates, including the formation of 3
      nitrotyrosine. Fast kinetic techniques, electron paramagnetic resonance (EPR)
      studies, bioanalytical methods, and kinetic simulations have all assisted in
      characterizing and fingerprinting the reactions of tyrosine with peroxynitrite
      and one-electron oxidants and its further evolution to 3-nitrotyrosine. Recent
      findings show that nitration of tyrosines in proteins associated with
      biomembranes is linked to the lipid peroxidation process via a connecting
      reaction that involves the one-electron oxidation of tyrosine by lipid peroxyl
      radicals (LOO(*)).  Second, immunochemical and proteomic-based studies indicate
      that protein tyrosine nitration is a selective process in vitro and in vivo,
      preferentially directed to a subset of proteins, and within those proteins,
      typically one or two tyrosine residues are site-specifically modified. The nature
      and site(s) of formation of the proximal oxidizing or nitrating species, the
      physicochemical characteristics of the local microenvironment, and the structural
      features of the protein account for part of this selectivity. How this relatively
      subtle chemical modification in one tyrosine residue can sometimes cause dramatic
      changes in protein activity has remained elusive. Herein, I analyze recent
      structural biology data of two pure and homogenously nitrated mitochondrial
      proteins (i.e., cytochrome c and manganese superoxide dismutase, MnSOD) to
      illustrate regioselectivity and structural effects of tyrosine nitration and
      subsequent impact in protein loss- or even gain-of-function.

PMID- 23157447
TI  - Neurocognitive consequences of a paediatric brain tumour and its treatment: a
      meta-analysis.
AB  - AIM: This meta-analysis provides a systematic review of studies into intellectual
      and attentional functioning of paediatric brain tumour survivors (PBTS) as
      assessed by two widely used measures: the Wechsler Intelligence Scale for
      Children (3rd edition; WISC-III) and the Conners' Continuous Performance Test
      (CPT). METHOD: Studies were located that reported on performance of PBTS (age
      range 6-16y). Meta-analytic effect sizes were calculated for Full-scale IQ,
      Performance IQ, and Verbal IQ as measured by the WISC-III, and mean hit reaction
      time, errors of omission, and errors of commission as measured by the CPT.
      Exploratory analyses investigated the possible impacts of treatment mode, tumour
      location, age at diagnosis, and time since diagnosis on intelligence. RESULTS:
      Twenty-nine studies were included: 22 reported on the WISC-III in 710 PBTS and
      seven on CPT results in 372 PBTS. PBTS performed below average (p(s) <0.001) on
      Full-scale IQ (Cohen's d=-0.79), Performance IQ (d=-0.90), and Verbal IQ (d=
      0.54). PBTS committed more errors of omission than the norm (d=0.82, p<0.001); no
      differences were found for mean hit reaction time and errors of commission.
      Cranial radiotherapy, chemotherapy, and longer time since diagnosis were
      associated with lower WISC-III scores (p(s) <0.05). INTERPRETATION: PBTS have
      seriously impaired intellectual functioning and attentiveness. Being treated with
      cranial radiotherapy and/or chemotherapy as well as longer time since diagnosis
      leads to worse intellectual functioning.

PMID- 23157449
TI  - The relationship between personality disorders and Axis I psychopathology:
      deconstructing comorbidity.
AB  - The purpose of this review is (a) to study and systematically review the recent
      literature examining the co-occurrence and relationships between Axis I
      psychiatric disorders and Axis II personality disorders, specifically the six
      originally proposed for the Diagnostic and Statistical Manual of Mental Disorders
      (DSM)-5, and (b) to consider the clinical utility of the current Axis I and Axis
      II approach in the DSM-IV-TR and apply findings to state a position on the issue
      of collapsing together Axis I and Axis II. Community surveys or prospective
      cohort studies were reviewed as a priority. Our review indicates that the
      associations between clinical disorders and personality disorders clearly varied
      within each disorder and across the six personality disorders. Our understanding
      has advanced, particularly related to the clinical utility of comorbidity, and
      there may be sufficient evidence to support moving borderline personality
      disorder to Axis I. However, it seems premature to conclude that comorbidity is
      best conceptualized by having all disorders in a single category or by deleting
      disorders so that comorbidity is reduced. Our review suggests some priorities for
      future research into comorbidity, such as including personality disorders in
      future multivariate comorbidity models.

PMID- 23157448
TI  - How can we use our knowledge of alcohol-tobacco interactions to reduce alcohol
      use?
AB  - Currently, 8.5% of the US population meets criteria for alcohol use disorders,
      with a total cost to the US economy estimated at $234 billion per year. Alcohol
      and tobacco use share a high degree of comorbidity and interact across many
      levels of analysis. This review begins by highlighting alcohol and tobacco
      comorbidity and presenting evidence that tobacco increases the risk for alcohol
      misuse and likely has a causal role in this relationship. We then discuss how
      knowledge of alcohol and tobacco interactions can be used to reduce alcohol use,
      focusing on whether (a) smoking status can be used as a clinical indicator for
      alcohol misuse, (b) tobacco policies reduce alcohol use, and (c) nicotinic-based
      medications can be used to treat alcohol use disorders.

PMID- 23157451
TI  - Evaluation of MRI criteria for cavernous sinus invasion in pituitary
      macroadenoma.
AB  - BACKGROUND AND PURPOSE: This study was designed to evaluate various magnetic
      resonance imaging (MRI) criteria for cavernous sinus (CS) invasion in
      preoperative evaluation of pituitary macroadenoma. METHODS: The sellar MRIs of 63
      patients (47 female, 16 male; age 17-67 years, mean of 42 years) who underwent
      surgery for pituitary macroadenoma were retrospectively reviewed. The following
      MR signs were assessed and compared with intraoperative findings, and statistical
      analyses were performed: (1) presence of hypointense-line suggestive of medial
      wall of CS on high-resolution coronal T2-weighted image, (2) presence of entire
      rim-enhancement around the intracavernous internal carotid artery (ICA)
      ("periarterial enhancement"), (3) location of the tumor in relation to the
      lateral intercarotid lines, and (4) angle of tumor encasement around the
      intracavernous ICA. RESULTS: CS invasion was highly probable if periarterial
      enhancement was not depicted (positive predictive value, 86%; P < .001). Valuable
      criteria of CS invasion by logistic regression analysis were the absence of
      periarterial enhancement (P = .043, odds ratio = 5.23) and the angle of
      intracavernous ICA encased by the tumor (P = .029, odds ratio = 1.017) with a
      threshold value of 136.5 degrees  with a sensitivity of 90% and specificity of
      78.3%. CONCLUSIONS: MRI criteria may be helpful in evaluating the presence of CS
      invasion in pituitary macroadenoma.

PMID- 23157450
TI  - Ambulatory assessment.
AB  - Ambulatory assessment (AA) covers a wide range of assessment methods to study
      people in their natural environment, including self-report, observational, and
      biological/physiological/behavioral. AA methods minimize retrospective biases
      while gathering ecologically valid data from patients' everyday life in real time
      or near real time. Here, we report on the major characteristics of AA, and we
      provide examples of applications of AA in clinical psychology (a) to investigate
      mechanisms and dynamics of symptoms, (b) to predict the future recurrence or
      onset of symptoms, (c) to monitor treatment effects, (d) to predict treatment
      success, (e) to prevent relapse, and (f) as interventions. In addition, we
      present and discuss the most pressing and compelling future AA applications:
      technological developments (the smartphone), improved ecological validity of
      laboratory results by combined lab-field studies, and investigating gene
      environment interactions. We conclude with a discussion of acceptability,
      compliance, privacy, and ethical issues.

PMID- 23157452
TI  - 1,25-Dihydroxyvitamin D(3) (1,25-(OH)(2)D(3)) attenuates airway remodeling in a
      murine model of chronic asthma.
AB  - OBJECTIVES: 1,25-Dihydroxyvitamin D(3) (1,25-(OH)(2)D(3)) has immune- and
      inflammation-modulating properties in asthma, but its possible effects on
      asthmatic airway remodeling remain uncertain. In this study, we investigated the
      effects of 1,25-(OH)(2)D(3) on airway remodeling in a murine model of chronic
      asthma and investigated its role in regulating nuclear factor-kappaB (NF-kappaB)
      activation. METHODS: BALB/c mice were sensitized to ovalbumin (OVA) and
      subsequently exposed to intranasal OVA challenges for 9 weeks. Some mice also
      received an intraperitoneal injection of 1,25-(OH)(2)D(3) at the time of
      challenge. At the end of the challenge period, mice were evaluated for chronic
      airway inflammation and airway remodeling. Nuclear translocation of NF-kappaB p65
      in lung tissue was examined by Western blot. Inhibitor of NF-kappaB alpha
      (IkappaBalpha) expression was determined by real-time quantitative Reverse
      Transcription Polymerase Chain Reaction (RT-PCR) and Western blot. Phosphorylated
      IkappaBalpha protein expression was also determined by Western blot. RESULTS:
      1,25-(OH)(2)D(3) treatment reduced OVA-induced chronic inflammation in lung
      tissue and attenuated established structural changes of the airways, including
      subepithelial collagen deposition, goblet cell hyperplasia, and increased airway
      smooth muscle mass. 1,25-(OH)(2)D(3) also inhibited the nuclear translocation of
      NF-kappaB p65 in lung tissue. Concurrently, 1,25-(OH)(2)D(3) induced increased
      IkappaBalpha protein levels via inducing increased IkappaBalpha mRNA levels and
      decreased IkappaBalpha phosphorylation. CONCLUSION: 1,25-(OH)(2)D(3) could
      attenuate asthmatic airway remodeling and its inhibition of NF-kappaB activation
      may underlie this protective effect.

PMID- 23157453
TI  - Exploring the concept of respite.
AB  - AIM: To report an analysis of the concept of respite for older people.
      BACKGROUND: Respite is an important support strategy for family carers of older
      people. However, there is considerable confusion in the literature about the
      nature, scope, and outcomes of respite services. DATA SOURCES: The data source
      for the concept analysis was a review of literature addressing respite for older
      people. There were no publication date restrictions for the review and literature
      was searched up to 2010. DESIGN: Concept analysis that was informed by the work
      of Dubin and the operationalization of Dubin's work by Holton and Lowe. REVIEW
      METHOD: A review of the literature was undertaken to better understand the nature
      of respite for older people. The review investigated the views of respite from
      the perspective of the service provider, family carer, and care-recipient. A
      conceptual model of respite was developed using a four-step approach: gaining an
      understanding of the phenomenon; identifying and retrieving relevant studies;
      analysing the construct; and developing the conceptual model. RESULTS: The
      conceptual model that emerged from this process consisted of three attributes,
      Partnership, Service, and Respite. The attribute of Partnership concerned the
      relationship between the service provider, carer and care-recipient. The
      attribute of Service concerned what the provider offered and focused on two
      important areas, assistance and engagement. The attribute of Respite concerned
      the outcomes that the family carer and care-recipient gained from respite and
      focused on freedom, support, and connection. CONCLUSION: The conceptual model
      provides a framework to assist in the development of respite services.

PMID- 23157455
TI  - Coarse-grained model DNA: structure, sequences, stems, circles, hairpins.
AB  - A coarse-grained model for DNA that is intended to function realistically at the
      level of individual bases is reported. The model is composed of residues with up
      to eight coarse-grained beads each, which is sufficient for DNA-like base
      stacking and base-base recognition by hydrogen bonding. The beads interact by
      means of short-ranged pair potentials and a simple implicit solvent model.
      Movement is simulated by Brownian dynamics without hydrodynamic coupling. The
      main stabilizing forces are base stacking and hydrogen bonding, as modified by
      the effects of solvation. Complementary double-stranded chains of such residues
      form stable double helices over long runs (~10 MUs) at or near room temperature,
      with structural parameters close to those of B-form DNA. Most mismatched chains
      or mismatched regions within a complementary molecule melt and become disordered.
      Long-range fluctuations and elastic properties, as measured by bending and
      twisting persistence lengths, are close to experimental values. Single-stranded
      chains are flexible, with transient stretches of free bases in equilibrium with
      globules stabilized by intrastrand stacking and hydrogen bonding. Model DNAs in
      covalently closed loops form right- or left-handed supercoils, depending on the
      sign of overtwist or undertwist. Short stem-loop structures melt at elevated
      temperatures and reanneal when the temperature is carefully lowered. Overall,
      most qualitative properties of real DNA arise naturally in the model from local
      interactions at the base-pair level.

PMID- 23157454
TI  - Composite growth factor supplementation strategies to enhance tenocyte
      bioactivity in aligned collagen-GAG scaffolds.
AB  - Biomolecular environments encountered in vivo are complex and dynamic, with
      combinations of biomolecules presented in both freely diffusible (liquid-phase)
      and sequestered (bound to the extracellular matrix) states. Strategies for
      integrating multiple biomolecular signals into a biomimetic scaffold provide a
      platform to simultaneously control multiple cell activities, such as motility,
      proliferation, phenotype, and regenerative potential. Here we describe an
      investigation elucidating the influence of the dose and mode of presentation
      (soluble, sequestered) of five biomolecules (stromal cell-derived factor 1alpha
      [SDF-1alpha], platelet-derived growth factor BB [PDGF-BB], insulin-like growth
      factor 1 [IGF-1], basic fibroblast growth factor [bFGF], and
      growth/differentiation factor 5 [GDF-5]) on the recruitment, proliferation,
      collagen synthesis, and genomic stability of equine tenocytes within an
      anisotropic collagen-GAG scaffold for tendon regeneration applications.
      Critically, we found that single factors led to a dose-dependent trade-off
      between driving tenocyte proliferation (PDGF-BB, IGF-1) versus maintenance of a
      tenocyte phenotype (GDF-5, bFGF). We identified supplementation schemes using
      factor pairs (IGF-1, GDF-5) to rescue the tenocyte phenotype and gene expression
      profiles while simultaneously driving proliferation. These results suggest
      coincident application of multi-biomolecule cocktails has a significant value in
      regenerative medicine applications where control of cell proliferation and
      phenotype are required. Finally, we demonstrated an immobilization strategy that
      allows efficient sequestration of bioactive levels of these factors within the
      scaffold network. We showed sequestration can lead to a greater sustained
      bioactivity than soluble supplementation, making this approach particularly
      amenable to in vivo translation where diffusive loss is a concern and continuous
      biomolecule supplementation is not feasible.

PMID- 23157456
TI  - Models for predicting IKKA and IKKB blockade.
AB  - We describe the application of different methods in the development of QSAR
      models for IKKA and IKKB inhibition. The results show that the best QSAR models
      provide highly accurate predictions for existing IkB-kinase (IKK) inhibitors. The
      exceptions, corresponding to 5% of the known collection of inhibitors, are five
      classes of compounds incorporating the nitrile or sulfonamide moieties, small
      compounds with molecular weights of less than 300, and two classes of blockers
      considered to be type II kinase inhibitors. Comparison of our novel IKKB homology
      model and the recently reported IKKB crystal structure implies that a predictive
      protein-antagonist complex structure is more likely to exist as an inactive form
      in the crystalline state as observed in the recent protein X-ray structure.

PMID- 23157457
TI  - Anti-beta2 glycoprotein I antibodies and pregnancy outcome in antiphospholipid
      syndrome.
AB  - The relation between pregnancy outcome and single- or double-positivity of
      anticardiolipin (aCL) and beta2 glycoprotein I (abeta2GPI) in antiphospholipid
      syndrome (APS) has yet to be clearly documented. In this article, a total of 191
      lupus anticoagulant-negative pregnant women with primary APS were retrospectively
      divided into three groups: aCL(+) /abeta2GPI(-) ; aCL(+) /abeta2GPI(+) ; aCL(-)
      /abeta2GPI(+) . All women had received medical therapy consisting of prednisone
      (10-15 mg/day), low-dose aspirin (50 mg/day), and low molecular weight heparin
      (40 mg/day). The miscarriage rate in the double-positive group was significantly
      higher than that in the aCL(+) /abeta2GPI(-) group (46.2% vs. 22.1%, p < 0.05);
      the miscarriage rate in the aCL(-) /abeta2GPI(+) group (36.4%) was not
      significantly different from the rates of the other two groups (p > 0.05). Thus,
      double-positivity may be a risk factor for pregnancy loss and abeta2GPI antibody
      may be a better prognostic marker than aCL antibody for pregnancy outcome.

PMID- 23157458
TI  - The determinants of minimal levator hiatus and their relationship to the
      puborectalis muscle and the levator plate.
AB  - OBJECTIVE: To determine the muscles comprising the minimal levator hiatus.
      DESIGN: Cross-sectional study. SETTING: The University of Oklahoma Health
      Sciences Center, USA. POPULATION: Eight female fresh frozen pelves and 80
      nulliparouswomen. METHODS: Three-dimensional endovaginal ultrasound was performed
      in eight fresh frozen female pelves. The structures of the levator hiatus were
      tagged with needles and the cadavers were dissected to identify the tagged
      structures. A group of 80 nullipara underwent 3D endovaginal ultrasound, and the
      minimal levator hiatus area, puborectalis area, and anorectal angle were
      assessed, and normal values were obtained. MAIN OUTCOME MEASURES: Anatomic
      borders of minimal levator hiatus and normality in pelvic floor measurements.
      RESULTS: The pubococcygeus forms the inner lateral border and anterior attachment
      of the minimal levator hiatus to the pubic bone. The puboanalis fibres are
      immediately lateral to pubococcygeus attachments. There are variable
      contributions of the puborectalis fibres lateral to the puboanalis attachment.
      The posterior border of the minimal levator hiatus is formed by the levator
      plate. Eighty community-dwelling nulliparous women underwent 3D endovaginal
      ultrasound. The median age was 47 years (range 22-70 years). The mean of minimal
      levator hiatus and puborectalis hiatus areas were 13.4 cm(2) (+/-1.89 cm(2) SD)
      and 14.8 cm(2) (+/-2.16 cm(2) SD). The mean anorectal and levator plate descent
      angles were 156 degrees  (+/-10.04 degrees  SD) and 15.9 degrees  (+/-8.28
      degrees  SD). CONCLUSION: Anterior and lateral borders of the minimal levator
      hiatus are formed mostly by pubococcygeus. The puborectalis, pubococcygeus, and
      iliococcygeus form the bulk of the levator plate.

PMID- 23157459
TI  - Desulfofrigus sp. prevails in sulfate-reducing dilution cultures from sediments
      of the Benguela upwelling area.
AB  - Sediments of coastal upwelling areas are generally characterized by a high
      content of organic carbon that is mainly degraded via anaerobic microbial
      processes including sulfate reduction as a major terminal oxidation step. Despite
      the high importance of sulfate reduction in these sediments, the identity of
      sulfate-reducing bacteria (SRB) has remained almost unknown. Here, we applied a
      cultivation-based approach using selective enrichment conditions to study the
      diversity and distribution of active SRB in sediments along a transect
      perpendicular to the continental slope off the coast of Namibia (Meteor-cruise
      M76/1). To promote growth of the most abundant SRB, dilution series were prepared
      and amended with hydrogen, acetate, or a mixture of monomers representing typical
      substrates for SRB. Growth of SRB could be detected in the presence of all
      electron donors and from sediment down to 4 m depth. 16S rRNA gene-based DGGE
      analysis and sequencing revealed the predominance of SRB related to psychrophiles
      in particular to the genus Desulfofrigus, which made up 1 % of the total
      microbial community, accounting for an absolute abundance of up to 4.8 * 10(7) 
      cells mL(-1) . In general, the abundance of cultured SRB changed with depth and
      between the different sampling sites and correlated with the content of organic
      carbon as previously reported. Growth of chemolithotrophic SRB in relatively high
      dilution steps and the enrichment of methanogens as well as acetogens from deeper
      sediment point to a competition between hydrogen-utilizing microbial processes
      and their biogeochemical significance in deep sediment layers of the Benguela
      upwelling area.

PMID- 23157460
TI  - Result of extracorporeal irradiation and re-implantation for malignant bone
      tumors: a review of 30 patients.
AB  - AIMS: Extracorporeal irradiation and re-implantation (ECI) has been used as limb
      salvage surgery for musculoskeletal oncology patients. Biological reconstruction,
      no risk of disease transmission and immunological reaction, ready availability
      and preservation of bone stock are the major advantage of this surgical
      technique. This case series details the outcomes of ECI. METHODS: In total, 30
      patients (31 sites) were treated with ECI between 1996 and 2007. The mean
      survivor follow-up period was 47 months (at least 24 and up to 108). The results
      of ECI were judged in terms of recurrence and limb function. Surgical failure was
      defined as local recurrence and the need for amputation, and reoperation for any
      reasons. Functional status was assessed by three functional assessment systems:
      Mankin score, the Musculoskeletal Tumor Society score (MTSS) and the Toronto
      Extremity Salvage score (TESS). RESULTS: In all, 24 patients (80%) were alive and
      free from disease at last follow up. Operative failure occurred in two cases (7%)
      and the main complication was infection in three cases (10%). The mean values of
      the MTSS and the TESS were 82% (57-98%) and 81% (57-99.), respectively. Excellent
      or good results were achieved in 27 patients (90%) according to the Mankin score.
      Patients classified as stage IA and IIA, upper extremity and ECI-prosthesis
      composite, mostly demonstrated excellent results without any complications.
      CONCLUSION: Our results are encouraging in terms of the orthopedic and
      oncological outcomes. This indicates that ECI offers a good alternative method
      for reconstruction in limb salvage surgery.

PMID- 23157461
TI  - Synaptic plasticity and non-invasive brain stimulation in autism spectrum
      disorders.

PMID- 23157463
TI  - Photoassisted access to enantiopure conformationally locked ribofuranosylamines
      spiro-linked to oxazolidino-diketopiperazines.
AB  - N-Furoylated L-threonine-, serine-, or cysteine-based aminoacetals are coupled
      with o-aminoketones or aldehydes to offer rapid access to diverse enantiopure
      polyheterocycles possessing conformationally locked aminoglycoside-containing
      molecular scaffolds. The key step involves photogeneration of azaxylylenes which
      undergo [4 + 4] or [4 + 2] cycloadditions to the tethered furoyl pendants.

PMID- 23157464
TI  - Determinants of lipid goal achievement in patients on extended-release nicotinic
      acid/laropiprant in primary care clinical practice.
AB  - OBJECTIVES: To establish determinants of lipid goal attainment in primary care
      patients, with particular focus on participation in a disease management
      programme (DMP) on diabetes mellitus (DM) and/or coronary heart disease (CHD),
      with real-world practical relevance. METHODS: The present analysis was based on
      an observational study in 2359 patients with dyslipidaemia or
      hypercholesterolaemia that were treated with nicotinic acid 1000 mg/laropiprant
      20 mg (Tredaptive) one or two tablets daily. Subgroups were formed by DMP
      participation (DMP vs. no DMP). A stepwise logistic regression model with
      backward selection of variables was applied to investigate factors influencing
      the probability of reaching lipid goals. Follow-up was 23 +/- 7 weeks. RESULTS:
      Low density lipoprotein cholesterol (LDL-C) <100 mg/dl was achieved by 30.8% in
      DMP versus 26.8% (no DMP), high density lipoprotein (HDL-C) >40/50 mg/dl in 61.3%
      versus 66.1%, and triglycerides (TG) <150 mg/dl in 28.9% versus 31.7%. On
      multivariate analysis, age, sex, concomitant high-risk cardiovascular disease, or
      participation in a DMP appeared to have inconsistent effects on reaching LDL-C,
      HDL-C and TG goals. Likelihood to reach the LDL-C goal tended to be higher in
      males, in patients outside DMP, and in patients with DM or CHD, and those treated
      with 1 tablet (versus 2 tablets) extended release nicotinic acid 1000
      mg/laropiprant 20 mg. The likelihood of reaching the HDL-C goal was higher in
      males and in patients without DM or DM+CHD (no effect of DMP). The likelihood of
      reaching the TG goals was higher in females, in patients outside DMP, and in
      patients with DM and/or CHD. Limitations include potential bias due to study
      design, physician and patient selection, and missing values at follow-up.
      CONCLUSION: DMP participation was not associated with overall improved lipid goal
      attainment. Physicians cannot predict the magnitude of effects of newly initiated
      lipid modifying therapy based on baseline characteristics of their patients.

PMID- 23157465
TI  - Telmisartan plus amlodipine single-pill combination for the management of
      hypertensive patients with a metabolic risk profile (added-risk patients).
AB  - OBJECTIVE: Hypertensive patients with metabolic risk factors, including obesity,
      diabetes, and metabolic syndrome, often require a combination of antihypertensive
      agents to achieve blood pressure (BP) targets. This article considers the
      evidence supporting telmisartan/amlodipine combination therapy for the treatment
      of hypertension in patients with metabolic risk factors. METHODS: Clinical trials
      of telmisartan/amlodipine at doses of 40-80 mg/5-10 mg (T40-80/A5-10) in free,
      fixed-dose and single-pill combinations were identified through electronic
      searches (MEDLINE and congress abstracts) up to and including June 2012, and from
      the Boehringer Ingelheim (BI) trial database. All identified trials were reviewed
      for data on hypertensive patients with obesity, diabetes, or both. Post-hoc
      subgroup analyses were carried out using the BI database to determine the
      relevant information if it was not previously reported. RESULTS: Thirteen
      clinical trials including 6886 patients were identified with data relevant for
      inclusion in this review. The telmisartan/amlodipine combination allowed a high
      proportion of hypertensive patients with metabolic conditions to achieve BP
      targets, particularly among patients who had previously failed to achieve BP
      targets with monotherapy. BP reductions and goal rate achievement were similarly
      high among patients with and without the presence of metabolic risk factors. BP
      reductions were maintained throughout the 24 h dosing period, and 24 h goal rates
      were obtained in a high proportion of patients. Particularly large reductions in
      BP with telmisartan/amlodipine were recorded among patients with severe
      hypertension (systolic BP >=180 mmHg). CONCLUSIONS: The results of this post-hoc
      analysis further support the ability of the telmisartan/amlodipine combination to
      effectively reduce BP in hypertensive patients with obesity, diabetes, or
      metabolic syndrome, enabling the majority of patients to achieve target BP. This
      combination is also well tolerated, and may be considered a suitable option for
      these added-risk hypertensive patients.

PMID- 23157466
TI  - Population pharmacokinetics and pharmacodynamics of dalfampridine-ER in healthy
      volunteers and in patients with multiple sclerosis.
AB  - OBJECTIVE: Using data pooled from several studies of dalfampridine extended
      release (ER), a population pharmacokinetic model was developed for the purposes
      of characterizing the population pharmacokinetics and pharmacodynamics of
      dalfampridine-ER with respect to variability in pharmacokinetics, covariates
      affecting the pharmacokinetics, and whether the current therapeutic dosage
      represents an optimal dosage. Studies were conducted in healthy volunteers and
      multiple sclerosis (MS) patients over the course of development and registration
      of dalfampridine extended release tablets (dalfampridine-ER [Ampyra *]; prolonged
      , modified- or sustained-release fampridine [Fampyra ?] in some countries).
      METHODS: The model used to best describe the population pharmacokinetics of
      dalfampridine-ER was an open, one-compartment model with first-order absorption,
      first-order elimination and an absorption lag time. RESULTS: The population
      median estimated oral clearance was 36 L/h for a 50-year-old woman with a
      creatinine clearance of 105 mL/min and 42 L/h for a comparable man. The typical
      volume of distribution was 304 L for women and 403 L for men. The estimated
      absorption rate constant was 1.22 hours(-1) in the fasted state and 2.22 hours(
      1) when given with food. The covariates identified as having a significant effect
      (p < 0.01) on model fit were food and gender on absorption rate, and gender, age
      and creatinine clearance on oral clearance. Only creatinine clearance and age are
      of clinical relevance. Concomitant medications did not affect any of the
      parameters in the model. Exposure-response relationships for both efficacy and
      safety were consistent with what has been observed in clinical trials.
      Limitations of this study include some reliance on unpublished data, and the
      limited effectiveness of the model for determining the likelihood of the efficacy
      and safety of dalfampridine-ER in clinical practice. CONCLUSIONS: The approved
      therapeutic dosage regimen of dalfampridine-ER 10 mg twice daily was identified
      as the optimum dosing regimen based on model-predicted exposure response
      relationships for efficacy and adverse events. A limitation of this study is the
      limited effectiveness of the models used to predict long-term efficacy and safety
      of dalfampridine-ER in clinical use.

PMID- 23157467
TI  - Pharmacokinetic profile of dalfampridine extended release: clinical relevance in
      patients with multiple sclerosis.
AB  - BACKGROUND: In January 2010, dalfampridine extended release tablets
      (dalfampridine-ER [Ampyra *]; prolonged-, modified- or sustained-release
      fampridine [Fampyra ?] in some countries), 10 mg to be administered twice daily
      approximately 12 hours apart, were approved by the US Food and Drug
      Administration. This was the first drug indicated to improve walking in patients
      with MS. SCOPE: Publications describing the pharmacokinetics of dalfampridine-ER
      or the immediate release formulation were identified from a search of PubMed
      through June 2012 using the search terms 'dalfampridine OR fampridine OR 4
      aminopyridine' AND 'pharmacokinetics' and were supplemented with unpublished
      studies made available by Acorda Therapeutics Inc. FINDINGS: Pharmacokinetic
      studies show dose proportionality, with dalfampridine-ER having a more favorable
      profile than immediate-release dalfampridine. With twice-daily dosing of
      dalfampridine-ER, time to peak plasma concentration (3.2-3.9 hours) and apparent
      terminal plasma half-life (5.6-6.4 hours) are approximately twice those of
      immediate-release formulations, with comparable overall exposure and peak plasma
      concentrations (21.6 ng/mL) that were maintained at levels approximately 50%
      lower than immediate release. Steady state is achieved within 39 hours;
      pharmacokinetics are predictable based on single dosing. Trough plasma
      concentrations of 13-15 ng/mL are required to maintain efficacy. Renal excretion
      is predominantly as unchanged compound, and renal clearance in healthy
      individuals exceeds the glomerular filtration rate. Since dalfampridine-ER
      exposure increases with renal impairment, it is contraindicated in patients with
      moderate or severe impairment in the US, and in patients with any renal
      impairment in the European Union. CONCLUSIONS: Dalfampridine-ER has low protein
      binding, is not a substrate for p-glycoprotein and does not affect CYP450
      enzymes, suggesting a low potential for drug-drug interactions. Because of the
      narrow therapeutic range and risk of adverse events, including seizure, with
      increasing plasma concentrations, the recommended dose and regimen of
      dalfampridine-ER should not be exceeded and not be used with other dalfampridine
      formulations. A limitation of this review is that it includes some data that have
      not yet been published.

PMID- 23157468
TI  - Legitimacy in legacy: a discussion paper of historical scholarship published in
      the Journal of Advanced Nursing, 1976-2011.
AB  - AIMS: This paper presents a discussion of historical scholarship published in the
      Journal of Advanced Nursing. BACKGROUND: The Journal of Advanced Nursing provides
      a forum for disseminating high-quality research and scholarship. For over 35
      years, scholars have used the Journal of Advanced Nursing to disseminate research
      into aspects of nursing, including nursing history. DATA SOURCES: The data source
      was Wiley Online electronic database for the Journal of Advanced Nursing for the
      period 1976-December 2011. DISCUSSION: Relative to other academic concerns,
      nursing history represents a topic of limited concern to nursing scholars, as
      evidenced in published scholarship in the Journal of Advanced Nursing. The trends
      in historical scholarship in the journal have been on disciplinary development,
      the place and context of practice, and gendered relationships. While these are
      legitimate academic concerns, they suggest a lack of attention to clinical
      practice in historical research, that which confers social legitimacy on the
      discipline. IMPLICATIONS FOR NURSING: Nursing derives its social legitimacy, in
      part, through its history, including reliable accounts of the legacy of nursing
      work in the development of healthcare systems. Disciplinary development in
      nursing is advanced by giving greater prominence to nursing history in nursing
      scholarship, including the history of nursing practice CONCLUSIONS: Relative to
      other academic concerns, nursing scholarship affords little prominence to the
      topic of nursing history and less still to the history of practice, as evidenced
      in the outputs of one of nursing's major organs of scholarship. Not to assign due
      importance to the history of nursing and its practice demonstrates nursing's lack
      of disciplinary maturity.

PMID- 23157469
TI  - Bisphosphonates-related osteonecrosis of the jaws: a preliminary study of
      salivary interleukins.
AB  - OBJECTIVE: The aim of this preliminary study was analyze the possible alterations
      in some salivary interleukins, usually associated with the inflammatory
      processes. MATERIAL AND METHODS: The study comprised three groups: group 1, with
      26 cases with bisphosphonates-related osteonecrosis of the jaws (BRONJ). Group 2,
      with 29 patients who had received iBF but without BRONJ. Group 3, with 26 control
      patients not treated with BF and without oral lesions. We collected unstimulated
      whole saliva in all groups. A semiquantitative study was performed based on a
      cytokine array panel. We used the proteome profiler array for the study. We
      analyzed: Interleukin 1 alpha (IL-1alpha), interleukin-1 receptor antagonist (IL
      1RA), and interleukin 1 beta (IL-1beta). RESULTS: We found higher salivary values
      for all the cytokines studied in group 1 than in group 2 and 3. IL-1beta showed
      the major differences compared with control group. (P < 0.05) CONCLUSIONS: This
      preliminary study confirms that there are alterations in these interleukins in
      patients with BRONJ. These results give support to further additional salivary
      studies on these biomarkers by quantitative measures.

PMID- 23157471
TI  - [History of thoracic surgery: from the beginnings to the end of the 19th
      century].
AB  - The authors give an outline of the history of chest surgery from ancient times to
      the end of the 19th century. They point out the individual milestones of human
      knowledge which opened the pathway for successful surgical treatment of
      intrathoracic diseases after solving the many physiologic and pathophysiologic
      problems that had made these procedures impossible.

PMID- 23157472
TI  - [Traumatic rupture of thoracic aorta].
AB  - INTRODUCTION: Thoracic aortic injury (TAI) is burdened with high mortality (80
      90%). The diagnostic and therapeutic algorithm has changed radically over the
      last couple of years. The authors present their experience with diagnosis and
      treatment of TAI at the University Hospital Trauma Centre. MATERIAL AND METHODS:
      24 TAIs were evaluated in a retrospective study, in 20 (83.3%) cases they were
      part of a polytrauma. The average age of the patients was 39.4 years (20-67).
      Traffic accidents formed the majority of TAIs (87.5%). Multi-detector computed
      tomography was used as a basic examination to detect TAI. Thoracic endovascular
      aortic repair (TEVAR) was the treatment of choice in 21 and open surgery in 3
      injured patients. RESULTS: The 30-day postoperative mortality was 12.5%, in one
      case it was associated with TEVAR. 30-day morbidity was 37.5% (circulatory
      instability, respiratory insufficiency, bronchopneumonia, type I endoleak).
      CONCLUSION: MDCT and TEVAR are currently the methods of first choice in the
      diagnosis and treatment of TAI. TAI requires a highly specialized
      multidisciplinary approach within Trauma Centres providing complex cardiovascular
      services.

PMID- 23157473
TI  - [Idiopathic inflammatory bowel disease - advancements in surgical treatment].
AB  - INTRODUCTION: Treatment of idiopathic inflammatory bowel disease is constantly
      developing. Biological therapy has become a standard part of conservative
      treatment, and gene and cell therapy of these diseases is in preclinical phase.
      Surgical therapy also offers some progress in the treatment, such as the
      increasingly preferred laparoscopic approach offering the numerous benefits of
      minimally invasive surgery or a tendency to perform stapled anastomosis. MATERIAL
      AND METHODS: A retrospective analysis of patients with a diagnosis of idiopathic
      inflammatory bowel operated on at the First Department of Surgery, General
      University Hospital in the years 2007-2011 was performed. RESULTS: Within this
      period, 179 patients diagnosed with Crohns disease were operated on. 30 patients
      underwent acute operation and 149 patients were indicated for elective surgery.
      In the same period, 40 patients with ulcerative colitis were indicated for
      surgery, of whom 22 patients for acute surgery and 18 for elective surgery.
      CONCLUSION: Multidisciplinary approach in the treatment of patients with
      inflammatory bowel disease is crucial and patients should be treated in
      specialized centres. New possibilities of conservative treatment and progress in
      surgical therapy mutually correlate, and thus the choice of a correct therapeutic
      procedure requires specific cooperation between the surgeon and the
      gastroenterologist.

PMID- 23157470
TI  - Hair follicle: a novel source of multipotent stem cells for tissue engineering
      and regenerative medicine.
AB  - The adult body harbors powerful reservoirs of stem cells that enable tissue
      regeneration under homeostatic conditions or in response to disease or injury.
      The hair follicle (HF) is a readily accessible mini organ within the skin and
      contains stem cells from diverse developmental origins that were shown to have
      surprisingly broad differentiation potential. In this review, we discuss the
      biology of the HF with particular emphasis on the various stem cell populations
      residing within the tissue. We summarize the existing knowledge on putative HF
      stem cell markers, the differentiation potential, and technologies to isolate and
      expand distinct stem cell populations. We also discuss the potential of HF stem
      cells for drug and gene delivery, tissue engineering, and regenerative medicine.
      We propose that the abundance of stem cells with broad differentiation potential
      and the ease of accessibility makes the HF an ideal source of stem cells for gene
      and cell therapies. 

PMID- 23157474
TI  - [Protein S100b in differential diagnosis of brain concussion and superficial
      scalp injury in inebriated patients].
AB  - INTRODUCTION: Concussion cannot be differentiated from superficial scalp injury,
      especially in inebriated or uncooperative patients. This can have serious medical
      or forensic consequences. The aim of the study was to determine whether serum
      concentrations of S-100b in mild traumatic brain injury (MTBI) patients are
      significantly higher than those in patients with superficial scalp injury with
      scalp wound and alcohol intoxication. MATERIAL AND METHODS: A total of 50
      patients with head injury, 25 with mild concussion without scalp wound and
      alcohol intoxication, 25 superficial scalp injury patients with scalp wound and
      clinical signs of inebriety. Neurological status and cranial CT scan were
      evaluated 60-120 minutes after injury in all the 50 patients to exclude focal
      cerebral injury or skull fracture. RESULTS: The serum levels of S-100b were
      significantly increased in patients with concussion (median 0.36 +/- 0.15 MUg/l )
      in comparison with the group of patients with scalp injury and alcohol
      intoxication (median 0.09 +/- 0.002 MUg/l). All 50 patients had a normal cranial
      CT finding and neurological status. In all superficial scalp injury patients
      alcohol intoxication was confirmed (0.96 - 3.11s). CONCLUSION: We proved
      significantly higher values of S-100b in patients with brain concussion.
      Diagnostically decisive value of S-100b concentration in the serum was set at 146
      MUg/l and higher (94% sensitivity and 100% specificity). Alcohol intoxication (up
      to 3.11 s) and scalp wound seem to have had no crucial impact on serum S-100b
      level.

PMID- 23157475
TI  - [Anaplastic carcinoma of the thyroid gland].
AB  - INTRODUCTION: The characteristics of anaplastic carcinoma, its biological
      properties, incidence and possibilities of therapeutic influence are described in
      the article. MATERIAL AND METHODS: The authors present a cohort of patients with
      anaplastic carcinoma of the thyroid gland (ATC) who were operated on at the
      Department of Surgery during the last 5 years. RESULTS: The destiny of all the
      patients with histologically confirmed anaplastic carcinoma is followed, the
      survival period is evaluated. With regard to the small patient cohort there was
      no further statistical processing. CONCLUSION: The role of the surgeon in the
      treatment of anaplastic carcinoma as well as the necessity of the multimodal way
      of treatment is evaluated.

PMID- 23157476
TI  - [Catamenial pneumothorax  - case studies from our department in a ten-year
      period].
AB  - Catamenial pneumothorax is defined as spontaneous pneumothorax in women of
      reproductive age occurring in conjunction with the menstrual cycle. The authors
      present 4 cases of this condition treated in our department during the past ten
      years. The causes leading to the development of this condition and optimal
      treatment procedures are also discussed.

PMID- 23157477
TI  - [Rare internal hernia in the falciform ligament as a rare course  of abdominal
      emergency and infrequent  cause of ileus].
AB  - Intestinal obstruction caused by an internal hernia is considered to be a rare
      cause of ileus. The rarest of these is herniation through the falciform ligament.
      In our article we present the case of a 45-year old female patient operated on
      for small bowel herniation through a defect in the falciform ligament. The loops
      were laparoscopically repositioned into the free abdominal cavity and the defect
      was removed by electrocautery. After the operation the patient was stabilised and
      discharged into outpatient care. Our article also analyses relevant literature
      and the diagnostic methods because the abovementioned diagnosis is rare and often
      established as late as postoperatively. Key words:  internal hernia - the
      falciform ligament - iatrogenous defect in the falciform ligament.

PMID- 23157478
TI  - Acoustophoretic sorting of viable mammalian cells in a microfluidic device.
AB  - We report the first use of ultrasonic acoustophoresis for the label-free
      separation of viable and nonviable mammalian cells within a microfluidic device.
      Cells that have undergone apoptosis are physically smaller than viable cells, and
      our device exploits this fact to achieve efficient sorting based on the strong
      size dependence of acoustic radiation forces within a microchannel. As a model,
      we have selectively enriched viable MCF-7 breast tumor cells from heterogeneous
      mixtures of viable and nonviable cells. We found that this mode of separation is
      gentle and enables efficient, label-free isolation of viable cells from mixed
      samples containing 10(6) cells/mL at flow rates of up to 12 mL/h. We have
      extensively characterized the device, and we report the effects of piezoelectric
      voltage and sample flow rate on device performance and describe how these
      parameters can be tuned to optimize recovery, purity, or throughput.

PMID- 23157479
TI  - Stereocontrolled domino reactions.

PMID- 23157481
TI  - Development and Evaluation of Carbon Nanotubes Doped Sustained Release
      Microspheres of Metoprolol Tartrate.
AB  - A highly water soluble antihypertensive drug, metoprolol tartrate (MT) was
      selected as a model drug for preparation ofmulti-walled carbon nanotubes (MWCNTs)
      impregnated ethyl cellulose (EC) microspheres with aim to increase encapsulation
      efficiency and sustained release rate. Carbon nanotubesdrug adsorbate (MWCNTs:MT)
      loaded EC microspheres were optimized by Central Composite Design of experiment.
      The effects of independent variables (MWCNTs:MT and EC:adsorbate) were evaluated
      on responses like entrapment efficiency (EE) and time required for 50% drug
      release (t50). Furthermore, desirability approach was adopted to select best
      batch. The results revealed improvement in encapsulation efficiency for
      MWCNTs:MTloaded EC microspheres. In vitro drug release study exhibited complete
      release form drug alone microspheres within 14 h while MWCNTs impregnated EC
      microspheres exhibited only 50-60 % drug release in 14 h.The optimized batch was
      further characterized by various instrumental analysis which endorse
      encapsulation of MWCNTs:MT adsorbate inside the matrix of EC microspheres which
      resulted in enhanced encapsulation and sustained effect of MT.

PMID- 23157482
TI  - Obaid Siddiqi: celebrating his life in science and the cultural transmission of
      its values.

PMID- 23157480
TI  - Novel beta-catenin target genes identified in thalamic neurons encode modulators
      of neuronal excitability.
AB  - BACKGROUND: LEF1/TCF transcription factors and their activator beta-catenin are
      effectors of the canonical Wnt pathway. Although Wnt/beta-catenin signaling has
      been implicated in neurodegenerative and psychiatric disorders, its possible role
      in the adult brain remains enigmatic. To address this issue, we sought to
      identify the genetic program activated by beta-catenin in neurons. We recently
      showed that beta-catenin accumulates specifically in thalamic neurons where it
      activates Cacna1g gene expression. In the present study, we combined
      bioinformatics and experimental approaches to find new beta-catenin targets in
      the adult thalamus. RESULTS: We first selected the genes with at least two
      conserved LEF/TCF motifs within the regulatory elements. The resulting list of
      428 putative LEF1/TCF targets was significantly enriched in known Wnt targets,
      validating our approach. Functional annotation of the presumed targets also
      revealed a group of 41 genes, heretofore not associated with Wnt pathway
      activity, that encode proteins involved in neuronal signal transmission. Using
      custom polymerase chain reaction arrays, we profiled the expression of these
      genes in the rat forebrain. We found that nine of the analyzed genes were highly
      expressed in the thalamus compared with the cortex and hippocampus. Removal of
      nuclear beta-catenin from thalamic neurons in vitro by introducing its negative
      regulator Axin2 reduced the expression of six of the nine genes.
      Immunoprecipitation of chromatin from the brain tissues confirmed the interaction
      between beta-catenin and some of the predicted LEF1/TCF motifs. The results of
      these experiments validated four genes as authentic and direct targets of beta
      catenin: Gabra3 for the receptor of GABA neurotransmitter, Calb2 for the Ca(2+)
      binding protein calretinin, and the Cacna1g and Kcna6 genes for voltage-gated ion
      channels. Two other genes from the latter cluster, Cacna2d2 and Kcnh8, appeared
      to be regulated by beta-catenin, although the binding of beta-catenin to the
      regulatory sequences of these genes could not be confirmed. CONCLUSIONS: In the
      thalamus, beta-catenin regulates the expression of a novel group of genes that
      encode proteins involved in neuronal excitation. This implies that the
      transcriptional activity of beta-catenin is necessary for the proper excitability
      of thalamic neurons, may influence activity in the thalamocortical circuit, and
      may contribute to thalamic pathologies.

PMID- 23157483
TI  - Transcranial Doppler velocities in a large, healthy population.
AB  - BACKGROUND: Transcranial Doppler (TCD) ultrasonography has been extensively used
      in the evaluation and management of patients with cerebrovascular disease since
      the clinical application was first described in 1982 by Aaslid and colleagues TCD
      is a painless, safe, and noninvasive diagnostic technique that measures blood
      flow velocity in various cerebral arteries. Numerous commercially available TCD
      devices are currently approved for use worldwide, and TCD is recognized to have
      an established clinical value for a variety of clinical indications and settings.
      Although many studies have reported normal values, there have been few recently,
      and none to include a large cohort of healthy subjects across age, race, and
      gender. As more objective, automated processes are being developed to assist with
      the performance and interpretation of TCD studies, and with the potential to
      easily compare results against a reference population, it is important to define
      stable normal values and variances across age, race, and gender, with clear
      understanding of variability of the measurements, as well as the yield from
      various anatomic segments. METHODS: To define normal TCD values in a healthy
      population, we enrolled 364 healthy subjects, ages 18-80 years, to have a
      complete, nonimaging TCD examination. Subjects with known or suspected
      cerebrovascular disorders, systemic disorders with cerebrovascular effects, as
      well as those with known hypertension, diabetes, stroke, coronary artery disease,
      or myocardial infarction, were excluded. Self-reported ethnicity, handedness, BP,
      and BMI were recorded. A complete TCD examination was performed by a single
      experienced sonographer, using a single gate nonimaging TCD device, and a
      standardized protocol to interrogate up to 23 arterial segments. Individual
      Doppler spectra were saved for each segment, with velocity and pulsatility index
      (PI) values calculated using the instrument's automated waveform tracking
      function. Descriptive analysis was done to determine the mean velocities and PI,
      and all data were analyzed for changes by decade of age, sex race, handedness,
      BMI, and BP. RESULTS: Among the key intracranial segments, mean blood flow
      velocities (MBFV) were highest in the MCA and lowest in the PCA across all ages,
      sexes, and ethnic groups. There was no difference in the MBFVs between left and
      right side segments of the Circle of Willis, with the exception of the distal M1
      (P = .022) and the C1 (P < .0001), both slightly higher on the left. MBFV were
      higher among women than men in all segments except for the OA. MBFV decreased
      with advancing age in both men and women, but this was specific to Caucasian
      subjects. There were lower velocities in the OA for non-Caucasians. The PI was
      lower in the left VA (P < .0001), and for most segments was lower in women than
      men. The PI increased with age in all segments for women, but only in some
      segments for men, and this finding was also specific to Caucasian subjects. The
      yield of usable data ranged from 99.7% for the VA and BA, to 88.2% for C2.
      CONCLUSION: Our study provides normal, reference TCD values for a large cohort of
      healthy subjects across a wide range of age, sex, and race groups. We observed
      decreased MBFV and increased PI with aging, and higher MBFV in women. There were
      few differences in MBFV related to side or ethnicity, but the MFBV and PI changes
      with age were specific to Caucasians. We provide means and standard deviations of
      MBFVs across various demographic groups in key intracranial arteries. Such normal
      TCD values across age, gender, and ethnic groups in healthy subjects represent a
      useful reference tool for detecting individuals with TCD values outside normal
      limits and at increased vascular risk. TCD studies in large multiethnic
      populations are still required to determine differences in brain hemodynamics
      across various ethnic groups.

PMID- 23157484
TI  - Association genetics of chemical wood properties in black poplar (Populus nigra).
AB  - Black poplar (Populus nigra) is a potential feedstock for cellulosic ethanol
      production, although breeding for this specific end use is required. Our goal was
      to identify associations between single nucleotide polymorphism (SNP) markers
      within candidate genes encoding cellulose and lignin biosynthetic enzymes, with
      chemical wood property phenotypic traits, toward the aim of developing genomics
      based breeding technologies for bioethanol production. Pyrolysis molecular beam
      mass spectrometry was used to determine contents of five- and six-carbon sugars,
      lignin, and syringyl : guaiacyl ratio. The association population included 599
      clones from 17 half-sib families, which were successfully genotyped using 433
      SNPs from 39 candidate genes. Statistical analyses were performed to estimate
      genetic parameters, linkage disequilibrium (LD), and single marker and haplotype
      based associations. A moderate to high heritability was observed for all traits.
      The LD, across all candidate genes, showed a rapid decay with physical distance.
      Analysis of single marker-phenotype associations identified six significant
      marker-trait pairs, whereas nearly 280 haplotypes were associated with phenotypic
      traits, in both an individual and multiple trait-specific manner. The rapid decay
      of LD within candidate genes in this population and the genetic associations
      identified suggest a close relationship between the associated SNPs and the
      causative polymorphisms underlying the genetic variation of lignocellulosic
      traits in black poplar.

PMID- 23157485
TI  - Conformational exploration of two peptides and their hybrid polymer conjugates:
      potentialities as self-aggregating materials.
AB  - In this work we elucidate the conformational preferences of two amyloid-forming
      peptides, Arginine-Vasopressin and Neuromedin-K, and two new biomacromolecular
      conjugates obtained by linking the two peptides to a polyester (poly(R-lactic
      acid)) chain. The conformational properties of the new hybrid conjugates have
      been assessed through molecular dynamics simulations and compared to those of
      their individual components. Our results suggest that the free unconjugated
      peptides tend to adopt backbone arrangements which resemble a beta-hairpin shape,
      a conformation which has been reported to facilitate amyloid self-aggregation.
      The backbone conformational preferences of the unlinked peptides are maintained
      in the peptide-polymer hybrid. Yet significant differences in the side-chains
      nonbonding interactions patterns were detected between the two states. This
      suggests that the conformational profile of the peptides' backbones is preserved
      when linked to the polymer, maintaining the amyloid precursor-like structure.
      Additionally, several hydrodynamic parameters were computed for both the
      polylactic acid and for the conjugates: no significant differences were observed,
      which suggests that the peptide moiety of the hybrid does not significantly
      affect the conformational tendencies of the polymer chain. Combined, our results
      provide a conformational exploration of two amyloid-forming peptides and first
      steps toward the design of two feasible self-aggregating hybrid materials.

PMID- 23157487
TI  - Premenstrual syndrome and dysphoric disorder as risk factors for postpartum
      depression.
AB  - OBJECTIVE: To investigate a possible association between postpartum depression
      and premenstrual symptoms. DESIGN: Population-based cohort. SETTING: University
      Hospital, Sweden. POPULATION: During one year, May 2006 to June 2007, all
      delivering women in the hospital were asked to participate. METHODS: The
      participating women answered three questionnaires, at five days, six weeks and
      six months postpartum, containing the Edinburgh Postnatal Depression Scale (EPDS)
      and questions assessing previous premenstrual symptoms, medical history and life
      style. MAIN OUTCOME MEASURES: The woman's self-reported depressive case/control
      status, women with 12 or more points on the EPDS being considered as cases.
      RESULTS: Among the 2318 participating women, 7.1% had a history of premenstrual
      syndrome and 2.9% a history of premenstrual dysphoric disorder. Previous
      premenstrual syndrome/premenstrual dysphoric disorder was associated with self
      reported postpartum depression at five days, six weeks and six months postpartum.
      After stratification for parity, the associations remained significant solely
      among multiparas. CONCLUSIONS: There appears to be an association between a
      history of premenstrual symptoms and development of self-reported postpartum
      depression. Parity was identified as effect modifier. This finding is clinically
      important for health care professionals working in maternity care.

PMID- 23157486
TI  - Microbial community changes at a terrestrial volcanic CO2 vent induced by soil
      acidification and anaerobic microhabitats within the soil column.
AB  - CO2 capture and storage (CCS) in deep geological formations is one option
      currently evaluated to reduce greenhouse gas emissions. Consequently, the impact
      of a possible CO2 leakage from a storage site into surface environments has to be
      evaluated. During such a hypothetical leakage event, the CO2 migrates upwards
      along fractures entering surface soils, a scenario similar to naturally occurring
      CO2 vents. Therefore, such a natural analogue site at the Laacher See was chosen
      for an ecosystem study on the effects of high CO2 concentrations on soil
      chemistry and microbiology. The microbial activities revealed differences in
      their spatial distribution and temporal variability for CO2 -rich and reference
      soils. Furthermore, the abundance of several functional and group-specific gene
      markers revealed further differences, for example, a decrease in Geobacteraceae
      and an increase in sulphate-reducing prokaryotes in the vent centre. Molecular
      biological fingerprinting of the microbial communities with DGGE indicated a
      shift in the environmental conditions within the Laacher See soil column leading
      to anaerobic and potentially acidic microenvironments. Furthermore, the
      distribution and phylogenetic affiliation of the archaeal 16S rRNA genes, the
      presence of ammonia-oxidizing Archaea and the biomarker analysis revealed a
      predominance of Thaumarchaeota as possible indicator organisms for elevated CO2
      concentrations in soils.

PMID- 23157488
TI  - Assessments of sensory processing in infants: a systematic review.
AB  - AIM: The aim of the study was to evaluate the psychometric properties and
      clinical use of assessments of sensory processing function, within the first 2
      years of life, and to identify which assessment is the most appropriate and
      precise in measuring the construct of sensory processing. METHOD: The literature
      was comprehensively searched, and assessments used to measure sensory processing
      in infancy were systematically selected and reviewed for clinical use,
      reliability, validity, and responsiveness. RESULTS: Thirty-four assessments were
      identified; three met the predefined inclusion criteria. All discriminative
      assessments, the Sensory Rating Scale, and Infant/Toddler Sensory Profile are
      parent-reported questionnaires and can be administered from birth up to 3 years
      of age. The Test of Sensory Function in Infants is a performance-based assessment
      and is suitable for infants aged 4 to 18 months. Studies evaluating the
      psychometric properties of these three assessments differed in the properties
      addressed and reported poor to adequate reliability. INTERPRETATION: Selecting
      the most appropriate and precise assessment to measure sensory processing
      function in infancy will depend on the specific components of sensory processing
      that need to be evaluated, infant age, and what other sources of information are
      available about the infant's development.

PMID- 23157489
TI  - Impact of pharmacotherapy on interstage mortality and weight gain in children
      with single ventricle.
AB  - OBJECTIVE.: Infants with single ventricle physiology have a high mortality and
      poor somatic growth during the interstage period. We retrospectively assessed the
      impact of pharmacotherapy in this population using a multicenter database. DESIGN
      AND RESULTS.: Records for 395 patients (63.5% boys) with single ventricle were
      obtained from the National Pediatric Cardiology Quality Improvement Collaborative
      registry. Median of five medications were prescribed per patient at discharge
      after stage 1 palliation (interquartile range 3 to 6); the most common
      medications being aspirin (95.7%), diuretics (90.4%), angiotensin convertase
      enzyme inhibitors (37.7%), proton pump inhibitors (33.4%), H2 receptor blockers
      (30.6%), and digoxin (27.6%). Interstage mortality was 9.4%. Digoxin use was
      associated with lower risk of death (P =.03) on univariable analysis, however no
      single medication was an independent predictor on regression analysis. Change in
      weight-for-age z-score was studied as outcome of somatic growth with 36.3%
      patients showing a decrease during the interstage period. Total number of
      medications prescribed to a patient showed a negative correlation with the
      interstage change in z-score (r = -0.19, P =.002). On univariable comparisons,
      use of metoclopramide and lansoprazole were associated with decreased z-score (P
      =.004 and.041, respectively) although linear regression failed to identify any
      agent as independent predictor. CONCLUSIONS.: Children with single ventricle have
      high mortality and a profound medication burden. No individual medication is
      independently associated with better survival or weight gain during interstage
      period. Despite widespread use, proton pump inhibitors and prokinetic agents are
      not associated with better outcomes and may be associated with poor growth.

PMID- 23157490
TI  - Association of maternal education with the neuroblastoma susceptibility in
      children: a meta-analysis.
AB  - Maternal education might be an important factor for the neuroblastoma risk in
      children, but it was conflicting. This meta-analysis was performed to evaluate
      the relationship between maternal education and neuroblastoma susceptibility and
      to explore whether maternal education was an important indicator to be associated
      with the neuroblastoma risk in children. The association studies were identified
      from the databases of PubMed, and Cochrane Library as of June 1, 2012, and
      eligible investigations were synthesized using meta-analysis method. Results were
      expressed with odds ratios (OR) for dichotomous data, and 95% confidence
      intervals (CI) were also calculated. Six literatures were identified for the
      analysis of association between maternal education and neuroblastoma
      susceptibility in children, consisting of 2063 patients with cancer and 13,925
      controls. There was no a marked association between maternal education and
      neuroblastoma susceptibility when the maternal education was less than high
      school (OR = 0.66, 95% CI: 0.43-1.01, P = .06). We also found that maternal
      education was not associated with the neuroblastoma susceptibility when the
      maternal education was high school (OR = 0.74, 95% CI: 0.31-1.75, P = .49) and
      more than high school (OR = 0.78, 95% CI: 0.33-1.85, P = .58). In conclusion,
      maternal education is not associated with the neuroblastoma susceptibility in
      children. However, more investigations are required to further clarify the
      association of maternal education with the neuroblastoma susceptibility in
      children.

PMID- 23157491
TI  - Prevalence of metabolic syndrome in pre- and postmenopausal Iranian women.
AB  - BACKGROUND AND AIMS: The metabolic syndrome (MetS) is a constellation of risk
      factors increasing the risk of developing cardiovascular disease and diabetes.
      Little information is available on the association between MetS and menopausal
      status in Iranian women. Therefore, the purpose of the current study was to
      examine the prevalence and severity of MetS in pre- and postmenopausal women
      based on two commonly employed assessment criteria. METHODS: A total of 490
      premenopausal and 434 postmenopausal women from the Shiraz Women's Health Cohort
      Study were included in the study. MetS was defined according to the criteria of
      the National Cholesterol Education Program-Adult Panel Treatment III (NCEP
      ATPIII) and the International Diabetes Federation (IDF). Clinical, biochemical
      and anthropometric measures were collected from all study participants for
      determination of MetS. RESULTS: The majority of participants had at least two
      components of MetS. Postmenopausal women, compared to premenopausal women, had a
      higher prevalence of MetS. The prevalences of MetS were 60.2% and 59.4% based on
      the NCEP-ATPIII and IDF definitions, respectively. Waist circumference, waist-to
      hip ratio, blood pressure, and levels of fasting plasma glucose, total
      cholesterol, low density lipoprotein cholesterol, and triglycerides were higher
      in postmenopausal women compared to premenopausal women. CONCLUSIONS: MetS is a
      major threat to women's health and an aging population, and longitudinal studies
      to determine the mechanism of postmenopausal MetS are required.

PMID- 23157492
TI  - Evaluation of electrokinetic parameters for all DNA bases with sputter deposited
      nanocarbon film electrode.
AB  - The electrokinetic parameters of all the DNA bases were evaluated using a sputter
      deposited nanocarbon film electrode. It is very difficult to evaluate the
      electrokinetic parameters of DNA bases with conventional electrodes, and
      particularly those of pyrimidine bases, owing to their high oxidation potentials.
      Nanocarbon film formed by employing an electron cyclotron resonance sputtering
      method consists of a nanocrystalline sp(2) and sp(3) mixed bond structure that
      exhibits a sufficient potential window, very low adsorption of DNA molecules, and
      sufficient electrochemical activity to oxidize all DNA bases. A precise
      evaluation of rate constants (k) between all the bases and the electrodes is
      achieved for the first time by obtaining rotating disc electrode measurements
      with our nanocarbon film electrode. We found that the k value of each DNA base
      was dominantly dependent on the surface oxygen-containing group of the nanocarbon
      film electrode, which was controlled by electrochemical pretreatment. In fact,
      the treated electrode exhibited optimum k values for all the mononucleotides,
      namely, 2.0 * 10(-2), 2.5 * 10(-1), 2.6 * 10(-3), and 5.6 * 10(-3) cm s(-1) for
      GMP, AMP, TMP, and CMP, respectively. The k value of AMP was sufficiently
      enhanced by up to 33 times with electrochemical pretreatment. We also found the k
      values for pyrimidine bases to be much lower than those of purine bases although
      there was no large difference between their diffusion coefficient constants.
      Moreover, the theoretical oxidation potential values for all the bases coincided
      with those obtained in electrochemical experiments using our nanocarbon film
      electrode.

PMID- 23157493
TI  - Genetic analysis of DNA methylation and gene expression levels in whole blood of
      healthy human subjects.
AB  - BACKGROUND: The predominant model for regulation of gene expression through DNA
      methylation is an inverse association in which increased methylation results in
      decreased gene expression levels. However, recent studies suggest that the
      relationship between genetic variation, DNA methylation and expression is more
      complex. RESULTS: Systems genetic approaches for examining relationships between
      gene expression and methylation array data were used to find both negative and
      positive associations between these levels. A weighted correlation network
      analysis revealed that i) both transcriptome and methylome are organized in
      modules, ii) co-expression modules are generally not preserved in the methylation
      data and vice-versa, and iii) highly significant correlations exist between co
      expression and co-methylation modules, suggesting the existence of factors that
      affect expression and methylation of different modules (i.e., trans effects at
      the level of modules). We observed that methylation probes associated with
      expression in cis were more likely to be located outside CpG islands, whereas
      specificity for CpG island shores was present when methylation, associated with
      expression, was under local genetic control. A structural equation model based
      analysis found strong support in particular for a traditional causal model in
      which gene expression is regulated by genetic variation via DNA methylation
      instead of gene expression affecting DNA methylation levels. CONCLUSIONS: Our
      results provide new insights into the complex mechanisms between genetic markers,
      epigenetic mechanisms and gene expression. We find strong support for the
      classical model of genetic variants regulating methylation, which in turn
      regulates gene expression. Moreover we show that, although the methylation and
      expression modules differ, they are highly correlated.

PMID- 23157494
TI  - First cloning and characterization of two functional aquaporin genes from an
      arbuscular mycorrhizal fungus Glomus intraradices.
AB  - Arbuscular mycorrhizal (AM) symbiosis is known to stimulate plant drought
      tolerance. However, the molecular basis for the direct involvement of AM fungi
      (AMF) in plant water relations has not been established. Two full-length
      aquaporin genes, namely GintAQPF1 and GintAQPF2, were cloned by rapid
      amplification of cDNA 5'- and 3'-ends from an AMF, Glomus intraradices. Aquaporin
      localization, activities and water permeability were examined by heterologous
      expression in yeast. Gene expression during symbiosis was also analyzed by
      quantitative real-time polymerase chain reaction. GintAQPF1 was localized to the
      plasma membrane of yeast, whereas GintAQPF2 was localized to both plasma and
      intracellular membranes. Transformed yeast cells exhibited a significant decrease
      in cell volume on hyperosmotic shock and faster protoplast bursting on hypo
      osmotic shock. Polyethylene glycol (PEG) stimulated, but glycerol inhibited, the
      aquaporin activities. Furthermore, the expression of the two genes in arbuscule
      enriched cortical cells and extraradical mycelia of maize roots was also enhanced
      significantly under drought stress. GintAQPF1 and GintAQPF2 are the first two
      functional aquaporin genes from AMF reported to date. Our data strongly support
      potential water transport via AMF to host plants, which leads to a better
      understanding of the important role of AMF in plant drought tolerance.

PMID- 23157495
TI  - Poly(3-decylthiophene) radical anions and cations in solution: single and
      multiple polarons and their delocalization lengths in conjugated polymers.
AB  - Optical absorption spectra of anions and cations of poly(3-decylthiophene) (P3DT)
      in solution were identified as single polarons. Pulse radiolysis of P3DT in THF
      determined the spatial extent of one negative polaron to be ~11.5 thiophene units
      by observing transient absorption of P3DT(-*) radical ions, which are prinicpally
      free ions, at 850 nm with epsilon = (7.25 +/- 0.47) * 10(4) M(-1) cm(-1) and
      bleaching of the neutral absorption band at 450 nm. P3DT(-*) was formed in a
      combination of diffusive reactions and fast "step" processes. Similarly, a
      positive polaron of P3DT was estimated to delocalize over ~8.7 thiophene units by
      pulse radiolysis in chloroform. Chemical reduction by sodium and oxidation by
      FeCl(3) injected multiple charges into a single P3DT chain while showing
      absorption spectra in the early stages of reaction resembling those observed by
      pulse radiolysis. The results indicated that multiple polarons exist in a single
      chain of P3DT before coalescing into bipolarons or transforming into other forms
      of polaron.

PMID- 23157496
TI  - Rural placements are effective for teaching medicine in Australia: evaluation of
      a cohort of students studying in rural placements.
AB  - INTRODUCTION: Medical education in Australia is increasingly delivered through
      longitudinal placements in general practice and other community settings. Early
      meaningful exposure to patients has been shown to improve the transition from
      medical student to junior doctor. This study examines the experience of the first
      year cohort of the University of Western Sydney (UWS) Medical School long-term
      rural placement students. Results have been placed in the context of other
      published results for rural training schemes, comparing and contrasting the
      present results to those of others. METHODS: Students undertaking a rural
      placement in their final year of the UWS medical program (n = 21) participated in
      a mixed methods evaluation. Students filled out a quantitative survey, modified
      from a validated instrument, and also participated in a focus group. Class
      ranking of students, and changes over the time of their placement, were also
      examined. RESULTS: Overall, students were very pleased with their rural
      experience, both clinically and socially. Students found the rural experience
      more comprehensive than they had expected. They considered that they had a
      stronger learning experience in most aspects than they expect they would have
      received in a metropolitan area. The smaller realm of the medical world in a
      rural area was considered an advantage in providing more hands-on experience and
      more interprofessional team approaches to healthcare provision. It was also
      considered a drawback by some that more advanced cases of all kinds were sent out
      of the area to metropolitan hospitals. Between their ranking in the end of Year 3
      examination and the examination in the middle of Year 5, during which period
      students undertook their year-long placement, 14 of 22 students increased their
      class rank while two experienced no change and six decreased their class rank.
      Overall, the rural cohort advanced 4.2 places compared to their urban-placed
      peers. CONCLUSIONS: The present results confirm that rural placements have come
      into their own in Australia. Curriculum content regarding Aboriginal health
      issues should emphasise the complexity of culture and range of living conditions
      that makes up Aboriginal Australia and avoid a 'deficit-based perspective' that
      emphasises extreme cases over routine presentations. Taken together, the results
      reported by Australian medical schools now offering long-term rural placements
      suggest that rural long-term placements are at least as effective, and may even
      be more effective, than metropolitan hospital placements as an effective means of
      providing clinical education to medical students in their senior years.

PMID- 23157497
TI  - Sharing experiences to improve bereavement support and clinical care after
      stillbirth: report of the 7th annual meeting of the International Stillbirth
      Alliance.
AB  - Stillbirth remains a global health challenge which is greatly affected by social
      and economic inequality, particularly the availability and quality of maternity
      care. The International Stillbirth Alliance (ISA) exists to raise awareness of
      stillbirth and to promote global collaboration in the prevention of stillbirth
      and provision of appropriate care for parents whose baby is stillborn. The focus
      of this ISA conference was to share experiences to improve bereavement support
      and clinical care. These issues, relevant throughout the globe, are not discrete
      but closely interrelated, with both similarities and differences depending on the
      specific country and cultural context. Counting stillbirths and understanding the
      causes of stillbirth are essential not only for providing optimal care and
      support to parents whose babies die, but also for reducing the future burden of
      stillbirth. This summary highlights novel work from obstetricians, midwives,
      psychologists, parents and peer support organizations that was presented at the
      ISA meeting. It covers topics including the bereavement process, peer support for
      parents, support and training for staff, evidence for clinical care, and the need
      for accurate data on stillbirths and perinatal audits. Representatives from the
      maternity services of the region presented their outcome data and shared their
      experiences of clinical and bereavement care. Data and developments in practice
      within stillbirth and bereavement care must be widely disseminated and acted upon
      by those responsible for maternity care provision, both to prevent stillbirths
      and to provide high-quality care when they do occur.

PMID- 23157498
TI  - Cell bodies of the trigeminal proprioceptive neurons that transmit reflex
      contraction of the levator muscle are located in the mesencephalic trigeminal
      nucleus in rats.
AB  - Since the levator and frontalis muscles lack interior muscle spindles despite
      being antigravity mixed muscles to involuntarily sustain eyelid opening and
      eyebrow lifting, this study has proposed a hypothetical mechanism to compensate
      for this anatomical defect. The voluntary contraction of fast-twitch fibres of
      the levator muscle stretches the mechanoreceptors in Muller's muscle to evoke
      proprioception, which continuously induces reflex contraction of slow-twitch
      fibres of the levator and frontalis muscles. This study confirmed the presence of
      cell bodies of the trigeminal proprioceptive neurons that transmit reflex
      contraction of the levator and frontalis muscles. After confirming that severing
      the trigeminal proprioceptive fibres that innervate the mechanoreceptors in
      Muller's muscle induced ipsilateral eyelid ptosis, Fluorogold was applied as a
      tracer to the proximal stump of the trigeminal proprioceptive nerve in rats.
      Fluorogold labelled the cell bodies of the trigeminal proprioceptive neurons, not
      in any regions of the rat brain including the trigeminal ganglion, but in the
      ipsilateral mesencephalic trigeminal nucleus neighbouring the locus ceruleus.
      Some Fluorogold particles accumulated in the area of the locus ceruleus. The
      trigeminal proprioceptive neurons could be considered centrally displaced
      ganglion cells to transmit afferent signal from the mechanoreceptors in Muller's
      muscle to the mesencephalon, where they may be able to make excitatory synaptic
      connections with both the oculomotor neurons and the frontalis muscle motoneurons
      for the involuntary coordination of the eyelid and eyebrow activities, and
      potentially to the locus ceruleus.

PMID- 23157499
TI  - Improvement of length of survival of expanded flap by application of topical
      papaverine cream.
AB  - Blood flow in expanding tissue can be improved by papaverine through a special
      delivery system in early report. Because the delivery system was complex and
      inconvenient, another way of using papaverine was tested to observe the blood
      flow and the survival length of expanded flap in this study. Twenty-four pigs
      were divided into three groups randomly named A, B, and C. Four soft tissue
      expanders (150 millilitres) were implanted into each pig in group A and C.
      Another four modificatory rectangular expanders were implanted into each pig in
      group B. A laser Doppler blood velocimeter was used to measure the blood flow.
      During the expanding process, 1 gram (containing 2% hydrochloride papaverine) of
      hydrochloride papaverine cream was applied topically on the surface of each
      expanding skin in group A twice daily. Two millilitres of hydrochloride
      papaverine (containing 30 milligrams of hydrochloride papaverine) solution was
      injected into each outer shell of the modificatory expander in group B weekly.
      Group C acted as control group. A 15 * 3 centimetre random flap was evaluated
      from the expanded skin after expanding and the survival length measured. The
      value of blood flow increased more significantly in group A than groups B and C.
      There were statistical differences. The survival length of the expanded flap in
      group A was the longest among the three groups, and there were statistical
      differences too. This study shows that the survival length of expanded flap can
      be increased by application of papaverine cream topically during the expanding
      process.

PMID- 23157500
TI  - Psychiatric outcomes in operatively compared with non-operatively managed
      patients with facial trauma: Is there a difference?
AB  - Patients who sustain facial injury and who require an operation may be at greater
      risk for developing psychological distress and maladaptive coping. The purpose of
      this study was to examine psychological responses in adult victims of facial
      trauma after operation. A consecutive group of adult patients attending
      specialist outpatient clinics after facial trauma were evaluated for
      psychological distress. The subjects were divided into two groups based on
      whether their facial injuries were managed operatively or conservatively. The
      primary predictor variable in this study was surgical intervention. The main
      outcome variable was Hospital Anxiety and Depression Scale (HADS) scores. Chi
      squared, Mann Whitney U-test, and multiple regression analysis were used to
      analyse data. The sample consisted of 102 subjects; 71 patients had been managed
      operatively and 31 patients treated non-operatively. Psychometric scores
      suggestive of anxiety were present in 21% (n = 15) of the operatively managed
      group compared with 13% (n = 4) of the non-operatively managed group of patients.
      The prevalence of depression was comparable between both groups (14% compared
      with 13%). The median anxiety subscale scores for the operatively managed group
      when compared with the conservatively managed group of patients were
      significantly higher (6.6 compared with 4.4, p = 0.02); however, differences in
      the depression subscale scores did not reach statistical significance (6.2
      compared with 4.6, p = 0.06). This study shows an association between anxiety
      disorders and operative interventions in patients with facial trauma (HADS-A,
      beta = 2.2, p = 0.04). Similar rates of depression were found in the surgically
      and conservatively managed patients.

PMID- 23157501
TI  - Tunnelled lateral fasciocutaneous thoracodorsal flap with a skin island in breast
      reconstruction in oncoplastic breast surgery.
AB  - The technique and results of a tunnelled lateral fasciocutaneous flap with a skin
      island is described in immediate partial breast reconstruction in a subpopulation
      in oncoplastic breast surgery. Fifteen patients were operated on from January
      2008 to January 2011. The subpopulation consisted of patients with small or
      medium-sized breasts. All patients had invasive ductal carcinomas, located in the
      lateral or central parts of the breast, of which the lumpectomy in three cases
      included the nipple areola complex. Eleven patients had axillary lymph node
      dissection because of positive sentinel node biopsy. In four patients a re
      resection was performed due to insufficient primary resection margins. No primary
      or secondary mastectomies were performed. One haematoma at the site of
      reconstruction was registered as the only postoperative complication. No patient
      developed wound infection, delayed wound healing, seroma, or any flap
      complications. All patients had adjuvant chemotherapy and radiation therapy
      according to the guidelines of The Danish Breast Cancer Group. The patients were
      seen at follow-up visits at 14 days, 3, 12, and 24 months. No recurrences were
      seen during the observation time except for one patient, who had recurrence with
      dissemination of the disease and died 19 months postoperatively.

PMID- 23157502
TI  - Standardised measurements used to order compression garments can be used to
      calculate arm volumes to evaluate lymphoedema treatment.
AB  - Lymphoedema treatment outcome can be evaluated by calculating estimated limb
      volumes directly by water displacement (plethysmography; PG), or indirectly by
      circumference measurements (CM) and using the formula for a truncated cone. This
      study assessed the correlation between PG and circumference volume measurements
      to assess whether the correlation is acceptable, and if circumference
      measurements can be used to accurately assess arm volume. Ten women with
      unilateral lymphoedema after breast cancer treatment with a mean age of 66 (range
      50-83) years volunteered for arm volume estimates by PG and circumference
      measurements. The coefficient of variation (CV%) for all methods was calculated.
      Two Excel-based formulae of the truncated cone were developed; one for fixed 4-cm
      intervals leading to 10 volume segments (CM-10-VS), and one for varying intervals
      leading to four volume segments (CM-4-VS). The CV% was 0.609% for PG, 0.628% for
      CM-10-VS, and 0.632% for CM-4-VS. As expected, PG generated a significantly
      larger volume of both arms because it includes the hand. The difference between
      CM-10-VS and CM-4-VS measurements was not significant. All three measurement
      methods showed a high coefficient of correlation (0.813-0.915), and a high
      coefficient of regression (0.863-1.089). The excess volume, which is used to
      determine treatment outcome, showed the respective values of 0.932-0.978 and
      0.963-1.020, respectively. Using circumference measurements identical to those
      used when ordering made-to-measure compression garments speeds up volume
      measurements and can be used safely to evaluate lymphoedema treatment outcome.

PMID- 23157503
TI  - Glucose concentration in seromas after plastic surgery: a pilot study.
AB  - Previously, glucose concentration has been presumed to be similar in seroma,
      lymph, and plasma. However, there are few studies actually measuring glucose
      concentration in seroma. The aim of this pilot study was to determine if the
      glucose concentration in seroma is similar to that in plasma, as it has
      previously been presumed. Biochemical analysis of seroma was performed on 11
      patients that had undergone plastic surgery. Fluid was taken from the drains
      between postoperative day 3 and 6. The median glucose concentration was 3.09
      millimolar (mM) (range 2.25-3.89 mM). Glucose concentration in seroma does not
      seem to be similar to that of plasma and lymph that has previously been presumed.
      The result of this pilot study warrants further investigation to determine the
      span of normal glucose concentration, its development over time, its relation to
      plasma glucose concentration, and how it is affected by infection.

PMID- 23157504
TI  - Perforator-based fasciocutaneous flap for pressure sore reconstruction.
AB  - Pressure sore reconstruction is always a challenge for plastic surgeons due to
      its high recurrence rate. In addition to the myocutaneous flap, the perforator
      based fasciocutaneous flap has become a new entity used for pressure sore
      reconstruction. This study presents a series of 26 perforator-based
      fasciocutaneous flaps for pressure sore reconstruction, with good outcomes in 21
      patients from July 2008 to April 2011. The flaps were advanced, transposed, or
      rotated to obliterate the defects. Twenty of 26 flaps healed uneventfully without
      complication. One patient had a flap that totally necrosed, one had partial flap
      necrosis (flap rotated 180 degrees  in the above two cases), one had infection
      and healed by a secondary flap, one had minor wound dehiscence, one died of
      pneumonia 1 week postoperatively, and recurrence developed in one patient. The
      perforator-based fasciocutaneous flap is a reliable method and produced good
      results in this series. These flaps are well vascularised, have enough soft
      tissue bulk, and have a high degree of mobilisation freedom.

PMID- 23157505
TI  - Experience of 56 patients using a retrograde sural neurovascular flap to repair
      lower limb tissue defects.
AB  - This study was made to investigate the clinical effects of repairing lower limb
      defects with an improved retrograde sural nerve flap. From November 1996 to
      September 2010, a total of 56 patients with soft-tissue defects of the lower limb
      received improved retrograde sural neurocutaneous flap repair. There were 21
      women and 35 men ranging in age from 12-73 years (average age 45.9). Eight
      patients had dorsal foot defects, five patients had foot bottom defects, four
      patients had heel defects, six patients had defects around the ankle, and 15
      patients had defects below the lower third of the leg. Of these, 10 patients had
      exposed wounds and six cases had exposed tendons. The size of the surgical repair
      was between ~6 cm * 5 cm and ~25 cm * 9 cm. Four patients retained the donor's
      sural neurovascular flap and normal sural nerve function, and 10 patients
      retained the retrograde sural neurovascular flap with a thin layer of muscle. All
      grafted flaps survived in all 56 patients. Patient follow-up lasted between 3
      months and 3 years. The shape and function of their lower limbs were
      satisfactory. Two-point discrimination detection in the donor area and nerve
      control area revealed that the sensory function recovered well in the four
      patients with retained nerves. The partial necrosis of the distal flap in two
      patients healed successfully after dressing, and no other adverse reactions or
      complications were observed. Through clinical treatment of the 56 patients, good
      experience was accumulated. The operation methods made the flap blood supply more
      abundant, improved the survival rate, and retained the sensory function of the
      donor site of the lower limb flap. This reduced the damage to the donor site and
      made the operation safer.

PMID- 23157506
TI  - Open accurate reduction for irreducible mallet fractures through a new pulp
      traction technique with primary tendon repair.
AB  - Sixteen patients with bony mallet fingers were treated by a new technique of open
      reduction through a T-shaped dorsal incision and oblique wire fixation via pulp
      traction with additional primary extensor repair. Surgical indications included
      fractures with intra-articular involvement over 1/3 of the articular surface,
      distal phalanx subluxation, and displacement greater than 3 mm irreducible by
      extension block pinning. The cases were analysed prospectively for a mean follow
      up period of 12 months. The results were evaluated using Crawford's criteria.
      Eleven cases were evaluated as excellent, three cases as good, and two cases as
      fair. Complications included three cases with transient nail deformity, two cases
      with flexion limitation of 5 degrees  and 10 degrees , and three cases with
      extension lag between 5 degrees -10 degrees . This new method of accurate
      reduction achieves good clinical outcomes, with comparatively less complications
      in mallet fractures irreducible to closed extension block reduction.

PMID- 23157507
TI  - Congenital dislocation of the extensor tendon of the hand.
AB  - Congenital dislocation of the extensor tendon is extremely rare. We report a case
      of bilateral dislocations in an 8-year-old boy, which were treated successfully
      with reconstruction of the sagittal band. We describe the technique and 18
      months' result.

PMID- 23157510
TI  - Disease detection and management via single nanopore-based sensors.

PMID- 23157511
TI  - Noninvasive continuous functional near-infrared spectroscopy combined with
      electroencephalography recording of frontal lobe seizures.
AB  - PURPOSE: To investigate spatial and metabolic changes associated with frontal
      lobe seizures. METHODS: Functional near-infrared spectroscopy combined with
      electroencephalography (EEG-fNIRS) recordings of patients with confirmed
      nonlesional refractory frontal lobe epilepsy (FLE). KEY FINDINGS: Eighteen
      seizures from nine patients (seven male, mean age 27 years, range 13-46 years)
      with drug-refractory FLE were captured during EEG-fNIRS recordings. All seizures
      were coupled with significant hemodynamic variations that were greater with
      electroclinical than with electrical seizures. fNIRS helped in the identification
      of seizures in three patients with more subtle ictal EEG abnormalities.
      Hemodynamic changes consisted of local increases in oxygenated (HbO) and total
      hemoglobin (HbT) but heterogeneous deoxygenated hemoglobin (HbR) behavior.
      Furthermore, rapid hemodynamic alterations were observed in the homologous
      contralateral region, even in the absence of obvious propagated epileptic
      activity. The extent of HbO activation adequately lateralized the epileptogenic
      side in the majority of patients. SIGNIFICANCE: EEG-fNIRS reveals complex spatial
      and metabolic changes during focal frontal lobe seizures. Further
      characterization of these changes could improve seizure detection, localization,
      and understanding of the impact of focal seizures.

PMID- 23157512
TI  - Melody valve erosion into the ascending aorta.

PMID- 23157513
TI  - Interferometry and fluorescence detection for simultaneous analysis of labeled
      and unlabeled nanoparticles in solution.
AB  - A novel fluctuation spectroscopy technique based on interferometry is described.
      The technique, termed scattering interference correlation spectroscopy (SICS),
      autocorrelates the signals from the forward-scattered and transmitted laser light
      from nanoparticles (NPs) in solution. SICS has two important features: First, for
      unlabeled NPs with known refractive index, it analyzes not only the diffusion
      coefficient but also the effective cross section and concentration in a single
      measurement. Second, it can be combined with fluorescence correlation
      spectroscopy (FCS) for simultaneous analysis of labeled and unlabeled NPs. SICS
      is here demonstrated on unlabeled M13 phages and on unlabeled NPs with diameters
      of 210 nm down to 26 nm. It is also shown how the combination of SICS and FCS can
      be used to determine the fraction of fluorescent NPs in a mixture and estimate
      K(d) from a single binding measurement.

PMID- 23157514
TI  - The tumour suppressor DiRas3 interacts with C-RAF and downregulates MEK activity
      to restrict cell migration.
AB  - BACKGROUND INFORMATION: The mitogenic pathway, composed of RAF kinases, mitogen
      activated protein kinase kinases (MEK) and extracellular signal-regulated kinases
      (ERK), promotes cell proliferation and migration and is upregulated in many
      tumours. DiRas3 (ARHI, Noey2), a mainly GTP-bound Ras-like protein with an
      unusual N-terminal extension, is predominantly lost in ovarian and breast
      cancers. Its re-expression in these tissues impairs cell proliferation,
      autophagy, apoptosis and cell migration. Further, loss of DiRas3 correlates with
      an increase in growth factor-induced ERK phosphorylation. Therefore, DIRAS3
      proves to be a curious gene with remarkable tumour suppressing capabilities.
      However, how DiRas3 interferes with ERK phosphorylation, has remained unknown.
      RESULTS: We demonstrate that DiRas3 associates in vivo with C-RAF and directly
      binds in vitro to C-RAF, which is upstream of MEK and ERK. Direct binding of
      DiRas3 to C-RAF is nucleotide independent, and DiRas3's N-terminal extension
      alone is not sufficient for binding C-RAF. DiRas3 expression inhibits the
      activating phosphorylations of MEK and ERK. Serum-induced recruitment of DiRas3
      to the plasma membrane depends mainly on its N-terminal extension and less on its
      C-terminus, bound nucleotide or the presence of Ras-GTP. Correspondingly, removal
      of the N-terminal extension strongly decreases DiRas3's inhibition of MEK and ERK
      phosphorylations. Tyrosyl-phosphatases do not contribute significantly to
      reduction of ERK-phosphorylation byDiRas3. Consistently, downregulation of DiRas3
      results in a small but significant and persistent increase in MEK and ERK
      phosphorylation, but does not increase phosphorylation of P38, AKT and c-Jun NH2
      terminal kinase. Finally, downregulation of DiRas3 causes increased cell
      migration, through a mechanism that is MEK dependent. CONCLUSIONS: These results
      support a model in which serum signals induce the recruitment of DiRas3 to the
      plasma membrane, where it is tethered via its N- and C-termini. At the plasma
      membrane, DiRas3 interacts with C-RAF to specifically suppress the activating
      phosphorylations on MEK and ERK, thus restricting migration of non-cancer cells.
      This effect is relatively small, but it is also persistent, suggesting that it
      contributes to the maintenance of the non-migratory phenotype of non-cancerous
      tissues, in which DiRas3 is expressed.

PMID- 23157515
TI  - High exhaled nitric oxide levels may predict bronchial reversibility in allergic
      children with asthma or rhinitis.
AB  - BACKGROUND: Allergic asthma and rhinitis may be associated. Airway inflammation
      is shared by both disorders. The measure of the fractional concentration of
      exhaled nitric oxide (FeNO) may be considered as a surrogate marker for airway
      inflammation, mainly in allergic patients. Reversibility to bronchodilation (BD)
      testing is a functional characteristic of asthma. OBJECTIVE: The aim of this
      study was to evaluate whether FeNO may predict reversibility to BD in a pediatric
      cohort of allergic subjects with asthma (180) or rhinitis (150). METHODS: Lung
      function (including forced expiratory volume at the first second (FEV(1)), forced
      volume capacity (FVC), forced expiratory flow at 25-75% of volume capacity (FEF
      (25-75))), FeNO measurement, and BD testing were performed in all children.
      RESULTS: Lung function, FeNO, and sensitization type were significantly different
      in the two groups. A strong correlation was found between FeNO and DeltaFEV(1)
      after BD. Two main predictors of reversibility were FeNO values >34 ppb [Odds
      RatioAdj (ORAdj) = 1.9] and sensitization to perennial allergens (ORAdj = 1.7).
      CONCLUSIONS: This study provided evidence that FeNO was strongly related with the
      response to BD testing and could predict bronchial reversibility in children with
      allergic rhinitis or asthma. Therefore, a simple FeNO measurement could suggest
      relevant information about bronchial reversibility.

PMID- 23157516
TI  - Centralising care for cardiac arrest survivors in Australia.

PMID- 23157517
TI  - Leukaemias into the 21st century: part 1: the acute leukaemias.
AB  - The leukaemias are a biologically and clinically heterogeneous group of
      malignancies, which manifest as clonal expansions of a single cell at different
      stages of lympho-haemopoietic development. The transformed cell acquires an
      unrestrained capacity for self-renewal and, in the case of the acute leukaemias,
      also fails to differentiate into functional mature cells. Historically leukaemias
      were classified using a combination of clinical and (presumed) cell lineage
      criteria. Thus, the four major subgroups of acute and chronic myeloid leukaemia
      and acute and chronic lymphoid leukaemia were recognised. Up until the last 10-15
      years, patients within each major subgroup were treated along broadly similar
      lines. Genetic abnormalities have been recognised in certain leukaemias for over
      50 years; however, the recent explosion in our understanding of the frequency and
      complexity of molecular abnormalities in the leukaemias has 'opened the door' for
      the design of more targeted therapies with the expectation that their
      incorporation into therapeutic regimens will be associated with greater efficacy
      and less off-target toxicity.

PMID- 23157518
TI  - How we use recombinant activated Factor VII in patients with haemophilia A or B
      complicated by inhibitors. Working group of hematology experts from Australia and
      New Zealand, Melbourne, April 2011.
AB  - The management of bleeds in patients with haemophilia A or B complicated by
      inhibitors is complex. Recombinant activated Factor VII (rFVIIa; NovoSeven RT) is
      an established therapy in these patients. To develop a consensus-based guide on
      the practical usage of rFVIIa in haemophilia complicated by inhibitors, nine
      expert haemophilia specialists from Australia and New Zealand developed practice
      points on the usage of rFVIIa, based on their experience and supported by
      published data. Practice points were developed for 13 key topics: control of
      acute bleeding; prophylaxis; surgical prophylaxis; control of breakthrough
      bleeding during surgery or treatment of acute bleeds; paediatric use; use in
      elderly; intracranial haemorrhage; immune tolerance induction; difficult bleeds;
      clinical monitoring of therapy; laboratory monitoring of therapy; concomitant
      antifibrinolytic medication; practical dosing. Access to home therapy with rFVIIa
      is important in allowing patients to administer treatment early in bleed
      management. In adults, 90-120 MUg/kg is the favoured starting dose in most
      settings. Initial dosing using 90-180 MUg/kg is recommended for children due to
      the effect of age on the pharmacokinetics of rFVIIa. In the management of acute
      bleeds, 2-hourly dosing is appropriate until bleeding is controlled, with
      concomitant antifibrinolytic medication unless contraindicated. The practice
      points provide guidance on the usage of rFVIIa for all clinicians involved in the
      management of haemophilia complicated by inhibitors.

PMID- 23157519
TI  - Nutritional status of long-term patients in the acute care setting.
AB  - The nutritional status of 926 patients (51.4% female) at an acute tertiary
      private hospital with a length of stay >=14 days was assessed using Subjective
      Global Assessment. The prevalence of malnutrition was 42.5% (37.2% length of stay
      of 14-27 days, 51.6% >=28 days). From logistic regression analysis, length of
      stay and age were independent predictors of malnutrition. It is important that
      the nutritional status of longer stay patients is monitored and appropriate
      nutrition support is commenced.

PMID- 23157520
TI  - Conflict of interest: will it ever end?
AB  - Despite the inclusion of investigator-industry pecuniary and non-pecuniary
      associations in published clinical trials, the benefit of such disclosures may be
      limited. Two recent pivotal phase III drug studies that raised conflict of
      interest issues are discussed. It is recommended that in the future, a firewall
      should be erected between industry and investigators.

PMID- 23157521
TI  - SPECT ventilation perfusion scanning with the addition of low-dose CT for the
      investigation of suspected pulmonary embolism.
AB  - Single-photon emission computed tomography (SPECT) ventilation perfusion (V/Q)
      scanning with low-dose computed tomography (LDCT) is an emerging imaging
      technique for investigation of suspected pulmonary embolism (PE). We aimed to
      estimate diagnostic utility of the combined technique using results from all
      patients referred in 2009 compared with final diagnosis and 6-month follow-up
      status. PE was diagnosed in 28 of 106 patients (26%), including in 2 of 80 (2%)
      with negative SPECT V/Q and LDCT. The estimated negative predictive value of
      SPECT V/Q for PE was 97%. LDCT was abnormal in 43 (41%) patients, including 41
      patients who had negative SPECT V/Q. In 29 (27%) patients, LDCT provided
      information on alternative pathologies that accounted for presenting symptoms,
      and the combined technique had a diagnostic yield of 52%.

PMID- 23157522
TI  - Healthcare burden of in-hospital gout.
AB  - The disease burden of inpatient gout has not been reported. Using a discharge
      diagnosis database and individual case record review, 77 patients who developed
      acute gout complicating a hospital admission for another reason were identified
      between January 2001 and April 2010 at The Townsville Hospital. A control group
      of 28 301 cases with identical principal diagnoses were similarly ascertained,
      along with a subgroup of 231 cases matched for age, gender and ethnicity.
      Patients with an admission complicated by acute gout stayed 6 days longer in
      hospital than matched control patients (9 days vs 3 days, P = 0.0005) with the
      same principal diagnoses and demographics. Patients with an attack of gout were
      more likely to be older, male or indigenous. Early diagnosis and appropriate
      treatment may help to reduce the healthcare costs of this overlooked disease.

PMID- 23157523
TI  - Increased mortality risk in congestive heart failure patients with comorbid sleep
      apnoea: 10-year follow up.
AB  - We aimed to determine the mortality rates of a congestive heart failure (CHF)
      research cohort during a 10-year follow up and compare survival between those
      with CHF only (controls), CHF and central sleep apnoea, and CHF and obstructive
      sleep apnoea. There was a significant detriment of survival in patients with
      CHF/central sleep apnoea compared with both CHF/obstructive sleep apnoea patients
      (mean survival time difference 3.8 years, P = 0.005) and controls (mean survival
      time difference 4.0 years, P = 0.01).

PMID- 23157524
TI  - A fatal case of 'magic mushroom' ingestion in a heart transplant recipient.

PMID- 23157525
TI  - Disseminated herpes simplex virus infection following epidermal growth factor
      tyrosine kinase inhibitor therapy for non-small-cell lung carcinoma.

PMID- 23157526
TI  - A dangerous combination: Fabry disease and factor V Leiden.

PMID- 23157527
TI  - Antibiotic treatment may exacerbate clozapine induced renal failure.

PMID- 23157528
TI  - Reducing polypharmacy Don Quixote style.

PMID- 23157529
TI  - Do shorter emergency department stays increase in-hospital mortality?

PMID- 23157531
TI  - Guidelines on guidelines - the impact of the Web.

PMID- 23157532
TI  - Correcting Morris et al. with respect to anaesthesia for neonatal circumcision.

PMID- 23157534
TI  - Evidence-based policy: circumcision of infant males.

PMID- 23157536
TI  - 'Circumcision of infant males' must warn doctors of possible criminal assault
      charges.

PMID- 23157537
TI  - Legal arguments opposing infant male circumcision are flawed.

PMID- 23157538
TI  - The giant waves of Osborn in brain death.

PMID- 23157539
TI  - Male circumcision.

PMID- 23157541
TI  - Microvascular imaging in acute ischemic stroke.
AB  - BACKGROUND: Microvascular imaging (MVI), a new ultrasound technology, is used to
      analyze brain perfusion at the patient's bedside. This study aims to evaluate the
      diagnostic and prognostic value of MVI in patients with acute ischemic stroke
      (AIS). METHODS: Nineteen patients suffering from AIS (mean age, 70.9 +/- 12.2
      years; 47% female; mean NIHSS-score, 12 +/- 8) were investigated within the first
      12 hours after symptom onset. We used the iU22 (Philips) system (S5-1 probe; low
      mechanical index; depth, 13 cm), and 2 bolus injections of an ultrasound contrast
      agent (2.4 mL SonoVue per injection). The area of maximal perfusion deficit
      (AMPD) was compared with infarction on follow-up cranial computed tomography (CT)
      and NIHSS score 24 hours after stroke onset. RESULTS: Of 19 patients, 15 patients
      (79%) had sufficient insonation conditions. Of these patients, 12 had
      infarctions. The sensitivity and specificity of detecting infarctions with
      ultrasound perfusion imaging were 91% and 67%, respectively. A significant
      correlation existed between the AMPD and NIHSS score at 24 hours after symptom
      onset (P= .023), and with occlusion of the internal carotid artery (P= .005).
      CONCLUSION: Performing bedside MVI in the early phase of AIS provides information
      on brain parenchyma perfusion and prognosis of AIS.

PMID- 23157542
TI  - Unfavorable influence of structured exercise program on total leisure-time
      physical activity.
AB  - In randomized controlled trials (RCTs), with customized structured physical
      exercise activity (SPEA) interventions, the dose of leisure-time physical
      activity (LTPA) should exceed the LTPA dose of the nonexercising control (C)
      group. This increase is required to substantiate health improvements achievable
      by exercise. We aimed to compare the dose of SPEA, LTPA, and total LTPA (SPEA +
      LTPA) between a randomized Nordic walking (NW) group, a power-type resistance
      training (RT) group, and a C group during a 12-week exercise intervention in
      obese middle-aged men (n = 144) with impaired glucose regulation. The dose of
      physical activity was measured with diaries using metabolic equivalents. No
      significant difference (P > 0.107) between the groups was found in volume of
      total LTPA. The volume of LTPA was, however, significantly higher (P < 0.050) in
      the C group than in the NW group, but not compared with the RT group. These
      results indicate that structured exercise does not automatically increase the
      total LTPA level, possibly, as a result of compensation of LTPA with structured
      exercise or spontaneous activation of the C group. Thus, the dose of total LTPA
      and the possible changes in spontaneous LTPA should be taken into account when
      implementing a RCT design with exercise intervention.

PMID- 23157543
TI  - A toolkit for bulk PCR-based marker design from next-generation sequence data:
      application for development of a framework linkage map in bulb onion (Allium cepa
      L.).
AB  - BACKGROUND: Although modern sequencing technologies permit the ready detection of
      numerous DNA sequence variants in any organisms, converting such information to
      PCR-based genetic markers is hampered by a lack of simple, scalable tools. Onion
      is an example of an under-researched crop with a complex, heterozygous genome
      where genome-based research has previously been hindered by limited sequence
      resources and genetic markers. RESULTS: We report the development of generic
      tools for large-scale web-based PCR-based marker design in the Galaxy
      bioinformatics framework, and their application for development of next
      generation genetics resources in a wide cross of bulb onion (Allium cepa L.).
      Transcriptome sequence resources were developed for the homozygous doubled
      haploid bulb onion line 'CUDH2150' and the genetically distant Indian landrace
      'Nasik Red', using 454TM sequencing of normalised cDNA libraries of leaf and
      shoot. Read mapping of 'Nasik Red' reads onto 'CUDH2150' assemblies revealed
      16836 indel and SNP polymorphisms that were mined for portable PCR-based marker
      development. Tools for detection of restriction polymorphisms and primer set
      design were developed in BioPython and adapted for use in the Galaxy workflow
      environment, enabling large-scale and targeted assay design. Using PCR-based
      markers designed with these tools, a framework genetic linkage map of over 800cM
      spanning all chromosomes was developed in a subset of 93 F(2) progeny from a very
      large F(2) family developed from the 'Nasik Red' x 'CUDH2150' inter-cross. The
      utility of tools and genetic resources developed was tested by designing markers
      to transcription factor-like polymorphic sequences. Bin mapping these markers
      using a subset of 10 progeny confirmed the ability to place markers within 10 cM
      bins, enabling increased efficiency in marker assignment and targeted map
      refinement. The major genetic loci conditioning red bulb colour (R) and fructan
      content (Frc) were located on this map by QTL analysis. CONCLUSIONS: The generic
      tools developed for the Galaxy environment enable rapid development of sets of
      PCR assays targeting sequence variants identified from Illumina and 454 sequence
      data. They enable non-specialist users to validate and exploit large volumes of
      next-generation sequence data using basic equipment.

PMID- 23157545
TI  - The development of antibody-based immunotherapy for methamphetamine abuse:
      immunization, and virus-mediated gene transfer approaches.
AB  - Methamphetamine is a highly addictive psychostimulant that has been seriously
      abused worldwide, and currently there are no approved medications for the
      treatment of its abuse. Conventional treatments for drug addiction mainly seek to
      use small molecule agonists or antagonists to target the drug receptors in the
      brain, but unfortunately it is difficult to find a similar small molecule for the
      treatment of methamphetamine dependence. Alternatively, anti-methamphetamine
      antibodies can sequester the drug in the bloodstream and reduce the amount of
      drug available to the central nervous system, acting as peripheral
      pharmacokinetic antagonists. This review describes the development of antibody
      based immunotherapies, classified into active and passive immunizations, for the
      treatment of methamphetamine addiction. Furthermore, an alternative therapeutic
      approach, using a recombinant adeno-associated virus-mediated gene transfer
      technique to achieve in vivo expression of characterized anti-methamphetamine
      monoclonal antibodies, is proposed in this article.

PMID- 23157544
TI  - Biomimetic collagen-hydroxyapatite composite fabricated via a novel perfusion
      flow mineralization technique.
AB  - Prevalent three-dimensional scaffolds for bone tissue engineering are mineralized
      collagen-hydroxyapatite (Col/HA) composites. Conventional mineralization
      techniques are either to coat collagen scaffold surfaces with minerals or to
      simply mix collagen and mineral nanoparticles together. These conventional in
      vitro collagen mineralization methods are different from the in vivo bone
      formation process and often result in scaffolds that are not suitable for bone
      tissue engineering. In this study, a unique perfusion-flow (i.e., dynamic) in
      conjunction with a previously described polymer-induced liquid-precursor (PILP)
      method was used to fabricate a porous Col/HA composite. The dynamic flow emulated
      the physiological extracellular fluid flow containing the mineralization ions,
      while the PILP method facilitated the deposition of the HA crystals within the
      collagen fibrils (i.e., intrafibrillar mineralization). By utilizing a dynamic
      PILP technique to mimic the in vivo bone formation process, the resultant Col/HA
      composite has a similar structure and compositions like human trabecular bone. A
      comparison of the dynamic and static mineralization methods revealed that the
      novel dynamic technique facilitates more efficient and homogenous mineral
      deposition throughout the Col/HA composite. The dynamic intrafibrillar
      mineralization method generated stiff Col/HA composites with excellent surface
      property for cell attachment and growth. The human mesenchymal stem cells
      cultured on the Col/HA composites quickly remodeled the scaffolds and resulted in
      constructs with an extensive cell-derived extracellular matrix network.

PMID- 23157546
TI  - In-vivo gene delivery by sonoporation: recent progress and prospects.
AB  - The increasing knowledge of cellular and molecular mechanisms of human diseases
      allows envisaging the gene therapy by sonoporation as an emerging and promising
      therapeutic alternative. Sonoporation combines the local application of
      ultrasound waves and the intravascular or intratissue administration of gas
      microbubbles. In such a way, the permeability of vessels and tissues to the
      poorly permeant molecules is transiently increased. Ultrasound based modality
      offers new opportunities since ultrasound can be easily focused on a target
      tissue or organ and hence gene delivery and expression should be limited to the
      insonified region. Consequently, it might be possible to develop an efficient and
      safe tissue- or organ-specific delivery method by microbubble targeting and
      focused ultrasound. This review focuses on the current knowledge of sonoporation
      fundamentals and mechanisms. The sonoporation procedure and current preclinical
      trials will be then presented. Finally, the new challenges of sonoporation will
      be discussed.

PMID- 23157547
TI  - Interleukin-15 in gene therapy of cancer.
AB  - Interleukin-15 (IL-15) exerts powerful stimulatory effects on lymphocyte subsets
      that result in antiviral and antitumoral activities. The functions of this
      cytokine are mainly mediated in a cell-to-cell contact fashion termed IL-15 trans
      presentation. This function is mediated by a cell which tethers IL-15 to its
      plasmatic membrane complexed to IL-15 receptor alpha (IL-15Ralpha). Such surface
      complexes interact with interleukin-2 receptor beta and gamma on the adjacent
      cell to elicit signaling. Unlike interleukin-2, IL-15 protects from activation
      induced cell death and does not promote regulatory cells. These features underlie
      its activity against transplanted tumors and its adjuvanticity in tumor and viral
      vaccines. The GMP-manufactured recombinant protein is undergoing clinical trials
      but its rapid renal clearance calls for biotechnological strategies to increase
      molecular weight and ensure IL-15Ralpha. trans-presentation. Since early efforts
      with stable transfected tumor cells, IL-15 has been tested in a variety gene
      therapy approaches. Those mainly include transfer of expression cassettes to
      tumor cells, T cells, dendritic cells, vaccination sites and the liver as a
      biofactory organ. Detailed mechanistic knowledge of IL-15 biology is envisaged to
      make the most of a powerful immunotherapeutic tool ranked as one of the most
      promising for cancer immunotherapy.

PMID- 23157548
TI  - Transendocardial delivery of HGF via microbubbles and ultrasound to treat acute
      myocardial infarction.
AB  - To enhance the safety of transendocardial delivery and the efficacy of
      intramyocardial angiogenic gene expression, a visible, less invasive, targeted,
      high-efficiency gene delivery strategy was tested. Progress toward clinical
      approval of systemic administration of genes and microbubbles (MBs) has been
      limited. The feasibility of transendocardially delivering MBs as extracellular
      markers and gene carriers in conjunction with intracardiac ultrasound (US)
      treatment remains unknown. In a canine acute myocardial infarction (MI) model, a
      naked plasmid encoding 500 MUg human hepatocyte growth factor (HGF) was delivered
      transendocardially to the myocardium via US/MB (HGF-US/MB), insonation (HGFUS),
      or alone (HGF alone). Control MI dogs received saline without US/MB (control
      group). During US/MB, intracardiac insonation was performed for 30 s with a 10-s
      pause, at 4.3-MHz, 1-W/cm(2), for 60 s at each site. Gene and MB distribution in
      the myocardium was visualized. Compared to the HGF alone group at 28 days, the
      HGF-US/MB group had an average 7.1-fold enhancement in gene expression (P <
      0.01). Compared to the control group, there were 16% decreases in the ratio of
      left ventricle (LV) weight/body weight in the HGF-US/MB group and decreases in
      collagen volume fraction (CVF) of type I (33%) and type III (23%) collagen.
      Capillary density increased from 22.8 +/- 6.3/mm(2) in the control group to 154.3
      +/- 42.9/mm(2) in the HGF-US/MB group (P < 0.01). This less invasive catheter
      based US therapeutic procedure offers observable gene delivery with higher
      therapeutic efficiency, enhanced angiogenesis, and improved myocardial perfusion
      and ventricular function following MI.

PMID- 23157549
TI  - NK cell-associated antigen expression in retinoblastoma animal model.
AB  - Natural killer (NK) cells are critical components of our immune system. Herein,
      we for the first time analyzed the expression and localization of the activating
      receptor NK cell lectin-like receptor gene 2D (NKG2D) ligands, HLA-G, MICA,
      MICA/B, and ULBP-2 in orthotopic transplantation models of retinoblastoma.
      Interestingly, HLA-G and MICA/B were expressed in retinoblastoma cell, whereas
      MICA and ULBP-2 were not detected. Moreover, HLA-G and MICA/B were primarily
      detected in proliferative area of the tumor periphery with high Ki-67
      immunostaining. Our results suggest that NKG2D ligands are differentially
      expressed in retinoblastoma, which would play a crucial role in immunomodulation
      in retinoblastoma.

PMID- 23157550
TI  - Exploring the dynamics of four RNA-dependent RNA polymerases by a coarse-grained
      model.
AB  - In this article, we present a hybrid ENM/MARTINI coarse-grained model and examine
      the impact of reduced chemical detail on both static and dynamic properties by
      comparing against explicit atomistic simulations. This methodology complements
      the advanced molecular characterization and dynamics of proteins for medical and
      bioengineering applications by developing a fundamental understanding of how the
      motion and molecular characteristics of proteins, viruses, their precursors, and
      their interactions with the environment govern their behavior in different
      populations. As an example, we explore the dynamics of RNA-dependent RNA
      polymerases (RdRPs) from the following viruses: poliovirus, Coxsackie virus B3,
      human rhinovirus 16, and foot-and-mouth-disease virus. The hybrid coarse-grained
      model allows the microsecond time scales of interest for biological functions to
      be explored. Additionally, the ENM/MARTINI model captures the main features
      obtained from atomistic MD simulations for each of the RdRPs studied herein,
      including the higher flexibility of the pinky finger and thumb regions, as well
      as collective motions that might contribute significantly to the conformational
      transition between the open and closed states.

PMID- 23157551
TI  - Universal anion detection by replacement-ion chromatography with an atmospheric
      pressure solution-cathode glow discharge photometric detector.
AB  - A new method of detection for ion chromatography (IC) is described that couples
      replacement-ion chromatography (RIC) with an atmospheric-pressure solution
      cathode glow discharge (SCGD). In the new instrument, a conventional suppressed
      IC arrangement is followed by a "replacement column" that consists of a cation
      exchange micromembrane suppressor continuously regenerated with Li(2)SO(4). In
      this arrangement analytes are stoichiometrically converted to Li salts when they
      pass through the replacement column and are introduced into the SCGD, where they
      are detected indirectly by atomic emission spectrometry. Though found to be
      unsuitable for cation determinations, the SCGD-RIC instrument shows good
      repeatability (<3.5% peak area relative standard deviation), approximately 4
      orders of linear dynamic range, universal calibration (similar molar sensitivity
      for anions of the same charge), and detection limits between 0.08 and 0.64
      MUg.mL(-1) (25-MUL injection) for several mono- and divalent anions. Deviations
      from the universal calibration were also observed and are critically evaluated.
      Optimal operating conditions are described, analytical figures of merit are
      presented, and background sources present in the system are characterized and
      explained.

PMID- 23157552
TI  - Therapeutic benefits from nanoparticles: the potential significance of
      nanoscience in diseases with compromise to the blood brain barrier.

PMID- 23157553
TI  - Identification and characterization of MYB-bHLH-WD40 regulatory complexes
      controlling proanthocyanidin biosynthesis in strawberry (Fragaria * ananassa)
      fruits.
AB  - Strawberry (Fragaria * ananassa) fruits contain high concentrations of
      flavonoids. In unripe strawberries, the flavonoids are mainly represented by
      proanthocyanidins (PAs), while in ripe fruits the red-coloured anthocyanins also
      accumulate. Most of the structural genes leading to PA biosynthesis in strawberry
      have been characterized, but no information is available on their transcriptional
      regulation. In Arabidopsis thaliana the expression of the PA biosynthetic genes
      is specifically induced by a ternary protein complex, composed of AtTT2
      (AtMYB123), AtTT8 (AtbHLH042) and AtTTG1 (WD40-repeat protein). A strategy
      combining yeast-two-hybrid screening and agglomerative hierarchical clustering of
      transcriptomic and metabolomic data was undertaken to identify strawberry PA
      regulators. Among the candidate genes isolated, four were similar to AtTT2, AtTT8
      and AtTTG1 (FaMYB9/FaMYB11, FabHLH3 and FaTTG1, respectively) and two encode
      putative negative regulators (FaMYB5 and FabHLH3?). Interestingly,
      FaMYB9/FaMYB11, FabHLH3 and FaTTG1 were found to complement the tt2-1, tt8-3 and
      ttg1-1 transparent testa mutants, respectively. In addition, they interacted in
      yeast and activated the Arabidopsis BANYULS (anthocyanidin reductase) gene
      promoter when coexpressed in Physcomitrella patens protoplasts. Taken together,
      these results demonstrated that FaMYB9/FaMYB11, FabHLH3 and FaTTG1 are the
      respective functional homologues of AtTT2, AtTT8 and AtTTG1, providing new tools
      for modifying PA content and strawberry fruit quality.

PMID- 23157554
TI  - Elective induction of labor and the risk of cesarean section in low-risk parous
      women: a cohort study.
AB  - OBJECTIVE: To estimate the association between elective induction of labor and
      cesarean section in low-risk parous women, and to assess whether the association
      is influenced by induction method. DESIGN: Cohort study. SETTING: University
      hospital in Sweden. POPULATION: Parous women without pregnancy complications or
      previous cesarean section, and with a planned vaginal term (37-41 weeks),
      singleton birth, in vertex position were included. METHODS: Information was
      collected from a local database containing prospectively entered antenatal and
      delivery data. Odds ratios for cesarean section were calculated using generalized
      estimating equations logistic regression and adjusted for parity, maternal age,
      gestational length, birthweight, use of epidural anesthesia and year of birth.
      MAIN OUTCOME MEASURES: Emergency cesarean section. RESULTS: Among 7973
      pregnancies that fulfilled the inclusion criteria, 343 (4%) had an elective
      induction of labor. Intravenous oxytocin was administered in 5% of these
      inductions, amniotomy was performed in 62%, and a cervical ripening agent was
      used in 33%. Electively induced labor more than doubled the risk of cesarean
      section compared with spontaneous labor onset (OR 2.5, 95% CI 1.4-4.2) and this
      risk was more than tripled when cervical ripening was used (OR 3.6, 95% CI 1.7
      7.6). CONCLUSIONS: In low-risk parous women, electively induced labor has an
      increased risk of emergency cesarean section compared with spontaneous onset
      labor. This risk increase is more pronounced if cervical ripening agents are
      required. Women need to be counseled about these risks before elective induction
      of delivery is decided.

PMID- 23157555
TI  - Mitochondria in vascular health and disease.
AB  - The eukaryote's mitochondrial network is perhaps the cell's most sophisticated
      and dynamic responsive sensing system. Integrating metabolic, oxygen, or danger
      signals with inputs from other organelles, as well as local and systemic signals,
      mitochondria have a profound impact on vascular function in both health and
      disease. This review highlights recently discovered aspects of mitochondrial
      function (oxygen sensing, inflammation, autophagy, and apoptosis) and discusses
      their role in diseases of both systemic and pulmonary vessels. We also emphasize
      the role of mitochondria as therapeutic targets for vascular disease. We
      highlight the intriguing similarities of mitochondria-driven molecular mechanisms
      in terms of both pathogenesis and therapies in very diverse diseases, such as
      atherosclerosis, pulmonary hypertension, and cancer, to support the foundation of
      a new field in medicine: mitochondrial medicine.

PMID- 23157556
TI  - The androgen receptor in health and disease.
AB  - Androgens play pivotal roles in the regulation of male development and
      physiological processes, particularly in the male reproductive system. Most
      biological effects of androgens are mediated by the action of nuclear androgen
      receptor (AR). AR acts as a master regulator of downstream androgen-dependent
      signaling pathway networks. This ligand-dependent transcriptional factor
      modulates gene expression through the recruitment of various coregulator
      complexes, the induction of chromatin reorganization, and epigenetic histone
      modifications at target genomic loci. Dysregulation of androgen/AR signaling
      perturbs normal reproductive development and accounts for a wide range of
      pathological conditions such as androgen-insensitive syndrome, prostate cancer,
      and spinal bulbar muscular atrophy. In this review we summarize recent advances
      in understanding of the epigenetic mechanisms of AR action as well as newly
      recognized aspects of AR-mediated androgen signaling in both men and women. In
      addition, we offer a perspective on the use of animal genetic model systems aimed
      at eventually developing novel therapeutic AR ligands.

PMID- 23157559
TI  - A dynamic model of the jump-to phenomenon during AFM analysis.
AB  - The measurement of the physical properties of surfaces on the nanoscale is a long
      standing problem, and the atomic force microscope (AFM) has enabled the
      investigation of surface energies and mechanical properties over a range of
      length scales. The ability to measure these properties for softer materials
      presents a challenge when interpreting data obtained from such measurements, in
      particular because of the dynamics of the compliant AFM microcantilever. This
      work attempts to better understand the interaction between an AFM tip and samples
      of varying elastic modulus, in the presence of attractive van der Waals forces. A
      theoretical model is presented in which the dynamics of the approach of an atomic
      force microscope cantilever tip toward a surface, prior to and during the van der
      Waals-induced jump-to phenomenon, are included. The cantilever mechanics
      incorporates the motion of the air through which the cantilever moves, the
      acceleration, inertia, and torque of the cantilever, and the squeezing of the
      fluid between the cantilever tip and the surface, leading to elastohydrodynamic
      lubrication and deformation of the substrate. Simulations of the cantilever
      approach are compared to measurements performed using an atomic force microscope,
      and the effect of cantilever drive velocity is investigated. Cantilevers
      presenting (1) spherical colloid probe tips and (2) pyramidal tips are employed,
      and substrates exhibiting Young's moduli of 3 MPa, 500 MPa, and 75 GPa are
      measured. The analysis presented could be extended to enhance understanding of
      dynamic phenomena in micro/nanoelectromechanical systems such as resonators and
      microrheometers, particularly those which contain soft materials and also where
      surface interactions are important.

PMID- 23157558
TI  - Large-scale preparation of Shiga toxin 2 in Escherichia coli for toxoid vaccine
      antigen production.
AB  - Enterohemorrhagic Escherichia coli (EHEC) causes hemorrhagic colitis, and in more
      severe cases, a serious clinical complication called hemolytic uremic syndrome
      (HUS). Shiga toxin (Stx)is one of the factors that cause HUS. Serotypes of Stx
      produced by EHEC include Stx1 and Stx2. Although some genetically mutated toxoids
      of Stx have been developed, large-scale preparation of Stx that is practical for
      vaccine development has not been reported. Therefore, overexpression methods for
      Stx2 and mutant Stx2 (mStx2) in E. coli were developed. The expression plasmid
      pBSK-Stx2(His) was constructed by inserting the full-length Stx2 gene, in which a
      six-histidine tag gene was fused at the end of the B subunit into the lacZalpha
      fragment gene of the pBluescript II SK(+) vector. An E. coli MV1184 strain
      transformed with pBSK-Stx2(His) overexpressed histidine-tagged Stx2 (Stx2-His) in
      cells cultured in CAYE broth in the presence of lincomycin. Stx2-His was purified
      using TALON metal affinity resin followed by hydroxyapatite chromatography. From
      1 L of culture, 68.8 mg of Stx2-His and 61.1 mg of mStx2-His, which was generated
      by site-directed mutagenesis, were obtained. Stx2-His had a cytotoxic effect on
      HeLa cells and was lethal to mice. However, the toxicity of mStx2-His was
      approximately 1000-fold lower than that of Stx2-His. Mice immunized with mStx2
      His produced specific antibodies that neutralized the toxicity of Stx2 in HeLa
      cells. Moreover, these mice survived challenge with high doses of Stx2-His.
      Therefore, the lincomycin-inducible overexpression method is suitable for large
      scale preparation of Stx2 vaccine antigens.

PMID- 23157560
TI  - Qualitative exploration of the career aspirations of rural origin health science
      students in South Africa.
AB  - INTRODUCTION: There is evidence in the literature that rural background
      significantly encourages eventual rural practice. Given the shortage of
      healthcare providers in rural areas, we need to explore ways of ensuring
      throughput and success of rural-origin students in health sciences. It is
      therefore important to understand who these students are, what motivates them and
      the factors involved in the formation of their career choices. METHODS: The aim
      of this study is to understand the aspirations of undergraduate health science
      students of rural origin with regard to their future career plans. The objectives
      of the study include to explore and identify the key issues facing rural-origin
      students with regard to their future career plans. Individual interviews were
      conducted with 15 health science students from two South African universities.
      Transcriptions were analyzed with the aid of Nvivo v8 (www.qsrinternational.com).
      RESULTS: The findings suggest health science students of rural origin studying at
      universities in the South African context face specific challenges related to the
      nature of the contrast between rural and urban life, in addition to the more
      generic adaptations that confront all students on entering tertiary education.
      CONCLUSION: In order to support rural students in their studies, academic,
      financial, emotional and social stressors need to be addressed. Universities
      should strengthen existing support structures as well as aid the development of
      further support that may be required.Key words: career plan, health science,
      rural background, South Africa.

PMID- 23157557
TI  - Functions of microRNAs in cardiovascular biology and disease.
AB  - In 1993, lin-4 was discovered as a critical modulator of temporal development in
      Caenorhabditis elegans and, most notably, as the first in the class of small,
      single-stranded noncoding RNAs now defined as microRNAs (miRNAs). Another eight
      years elapsed before miRNA expression was detected in mammalian cells. Since
      then, explosive advancements in the field of miRNA biology have elucidated the
      basic mechanism of miRNA biogenesis, regulation, and gene-regulatory function.
      The discovery of this new class of small RNAs has augmented the complexity of
      gene-regulatory programs as well as the understanding of developmental and
      pathological processes in the cardiovascular system. Indeed, the contributions of
      miRNAs in cardiovascular development and function have been widely explored,
      revealing the extensive role of these small regulatory RNAs in cardiovascular
      physiology.

PMID- 23157561
TI  - Influence of mediterranean diet on asthma symptoms, lung function, and systemic
      inflammation: a randomized controlled trial.
AB  - OBJECTIVE: The rapidly increasing prevalence of asthma in developed countries
      suggests an environmental cause. The benefits of Mediterranean diet (MD) in
      cardiovascular disease have been tentatively attributed to its anti-inflammatory
      properties. Asthma is an inflammatory disease and MD is associated with reduced
      asthma risk in epidemiological studies, but there are no reported interventional
      studies of MD in asthma. METHODS: In this 12-week open-label randomized trial, 38
      adults with symptomatic asthma were allocated to high-intervention (HI), low
      intervention (LI), and control groups. The first two groups were encouraged to
      adopt an MD and received multiple consultation sessions with a nutritionist,
      written advice, and vouchers for the purchase of appropriate foods. Food
      frequency questionnaires, asthma control questionnaires, asthma-related quality
      of life questionnaires (AQLQs), and spirometry were completed at the beginning
      and at the end of the study. RESULTS: The MDt score increased in the HI group (p
      < .001), indicating successful alteration of dietary behavior. Statistically,
      nonsignificant improvements were seen in spirometry and several AQLQ subdomains
      in the two intervention groups. No changes were seen in the asthma control or in
      inflammatory markers. CONCLUSIONS: The trial intervention has successfully
      altered the dietary behavior among adults with asthma. Small but consistent
      improvements were seen in quality of life and spirometry among the intervention
      group. The use of the MD to treat asthma is feasible and warrants evaluation in a
      larger study, powered to examine clinical endpoints.

PMID- 23157562
TI  - Cardiac injury in refractory status epilepticus.
AB  - PURPOSE: We sought to describe the spectrum of cardiac injury in refractory
      status epilepticus (RSE). METHODS: We reviewed all patients with RSE between 1999
      and 2011 at Mayo Clinic. RSE was defined as generalized convulsive or
      nonconvulsive status epilepticus (SE) that continued despite initial therapies.
      Exclusion criteria were age <18 years, anoxic SE, psychogenic SE, simple partial
      SE, absence SE, and repeat RSE. Patients were divided into those with (transient
      left ventricular [LV] dysfunction; electrocardiography [ECG] abnormality-new T
      wave inversion, ST elevation or ST depression, or QTc prolongation; and/or
      elevated blood troponin T levels) versus those without evidence of cardiac
      injury. KEY FINDINGS: We identified 59 consecutive patients with RSE. In 24
      patients no cardiac-specific diagnostic studies were obtained. Twenty-two of the
      remaining 35 patients demonstrated markers of cardiac injury. General anesthesia
      was necessary for control of seizures in 31 of 35 patients for 10.5 +/- 17.4
      days. Twenty-three patients had troponin levels drawn at onset of SE, of which
      nine were abnormal. ECG findings at onset of SE included ST elevation (11.4%), ST
      depression (5.7%), new T-wave inversion (37.1%), and nonspecific ST changes
      (37.1%). Cardiac arrhythmias included ventricular tachycardia/fibrillation
      (11.4%), atrioventricular block (2.9%), atrial fibrillation/flutter (20.0%),
      sinus bradycardia (48.6%), and sinus tachycardia (65.7%). Intervention was
      required for cardiac arrhythmias in 42.9%. QTc was prolonged in 22.9% of
      patients. One patient met criteria for non-ST-elevation myocardial infarction
      (NSTEMI). Three of 14 patients evaluated with ECG during SE demonstrated
      reversible systolic dysfunction. In-hospital mortality was 34.3%. Outcome was
      worse in the group with markers of cardiac injury but the difference was not
      statistically significant (p = 0.14). SIGNIFICANCE: Markers of cardiac injury are
      common in RSE and may be underrecognized in this population. These disturbances
      may require specific treatment and are often reversible. Routine performance of
      ECG and troponin followed by an echocardiography in those with repolarization
      abnormalities is probably justified. This was a biased sample of patients with
      severe RSE who had cardiac studies performed. The prevalence of findings in this
      study refers to this subgroup only.

PMID- 23157563
TI  - Metabolic approaches to understanding climate change impacts on seasonal host
      macroparasite dynamics.
AB  - Climate change is expected to alter the dynamics of infectious diseases around
      the globe. Predictive models remain elusive due to the complexity of host
      parasite systems and insufficient data describing how environmental conditions
      affect various system components. Here, we link host-macroparasite models with
      the Metabolic Theory of Ecology, providing a mechanistic framework that allows
      integrating multiple nonlinear environmental effects to estimate parasite fitness
      under novel conditions. The models allow determining the fundamental thermal
      niche of a parasite, and thus, whether climate change leads to range contraction
      or may permit a range expansion. Applying the models to seasonal environments,
      and using an arctic nematode with an endotherm host for illustration, we show
      that climate warming can split a continuous spring-to-fall transmission season
      into two separate transmission seasons with altered timings. Although the models
      are strategic and most suitable to evaluate broad-scale patterns of climate
      change impacts, close correspondence between model predictions and empirical data
      indicates model applicability also at the species level. As the application of
      Metabolic Theory considerably aids the a priori estimation of model parameters,
      even in data-sparse systems, we suggest that the presented approach could provide
      a framework for understanding and predicting climatic impacts for many host
      parasite systems worldwide.

PMID- 23157564
TI  - CLOPPA analysis of the molecular polarizability and the energy of strong
      intramolecular hydrogen bonds: resonance assisted?
AB  - The contributions from localized orbitals within the polarization propagator
      approach (CLOPPA) method is applied to investigate the influence of the pi system
      on the polarizability of the intramolecular hydrogen bond of malonaldehyde, in
      order to address if this linear response property provides evidence for the
      existence of the resonance assisted HB (RAHB) mechanism. On the same grounds,
      this influence on the energy of the hydrogen bond and the potential energy curve
      of the proton are also evaluated. Results obtained seem to confirm that the pi
      system delocalizes on the hydrogen bond region, and this effect of delocalization
      is partially responsible for the unusual strength of this intramolecular hydrogen
      bond.

PMID- 23157565
TI  - Generating a minimal set of templates for the hippocampal region in MR
      neuroimages.
AB  - OBJECTIVES: We detail a procedure for generating a set of templates for the
      hippocampal region in magnetic resonance (MR) images, representative of the
      clinical conditions of the population under investigation. METHODS: The first
      step is robust standardization of the intensity scale of brain MR images,
      belonging to patients with different degrees of neuropathology (Alzheimer's
      disease). So similar tissues have similar intensities, even across images coming
      from different sources. After the automatic extraction of the hippocampal region
      from a large dataset of images, we address template generation, choosing by
      clusterization methods a small number of the extracted regions. RESULTS: We
      assess that template generation is largely independent on the clusterization
      method and on the number and the clinical condition of the patients. The
      templates are chosen as the most representative images in a population. The
      estimation of the "minimum" number of templates for the hippocampal region can be
      proposed, using a metric based on the geometrical position of the extracted
      regions. CONCLUSIONS: This study describes a simple and easily reproducible
      procedure to generate templates for the hippocampal region. It can be generalized
      and applied to other brain regions, which may be relevant for neuroimaging
      studies.

PMID- 23157566
TI  - Exhaled nitric oxide concentration upon acute exposure to moderate altitude.
AB  - The purpose of this study was to assess immediate changes in the partial pressure
      of nitric oxide (NO) in exhaled gas (PE NO ) in healthy trained subjects who were
      acutely exposed to moderate altitude. One group of nine and another group of 20
      healthy subjects were exposed to an ambient pressure of 728 hPa (546 mmHg)
      corresponding to an altitude of 2800 m for 5 and 90 min, respectively, in an
      altitude chamber. PE NO was measured offline by sampling exhaled gas in tight
      metal foil bags at 5, 30, 60, and 90 min. A correction for increased expiratory
      flow rate due to gas density effects at altitude was performed (PE NO corr). PE
      NO was significantly decreased by 13-16%, while the fraction of NO in exhaled gas
      (FE NO) was increased by 16-19% compared to sea level. There was no significant
      change in PE NO corr after exposure to altitude for 5, 30, 60, and 90 min. We
      conclude that there was no change in PENO upon arrival at altitude after
      correcting for gas density effects on expiratory flow rate. Corrections for
      altitude effects must be done before comparing measurements performed at
      different altitudes when using measurements of FENO to monitor athletes who have
      asthma during training at altitude.

PMID- 23157567
TI  - Electro- and photodriven phase change composites based on wax-infiltrated carbon
      nanotube sponges.
AB  - Organic phase change materials are usually insulating in nature, and they are
      unlikely to directly trigger latent heat storage through an electrical way. Here
      we report a multifunctional phase change composite in which the energy storage
      can be driven by small voltages (e.g., 1.5 V) or light illumination with high
      electro-to-heat or photo-to-thermal storage efficiencies (40% to 60%). The
      composite is composed of paraffin wax infiltrated into a porous, deformable
      carbon nanotube sponge; the latter not only acts as a flexible encapsulation
      scaffold for wax but also maintains a highly conductive network during the phase
      change process (for both solid and liquid states). Uniform interpenetration
      between the nanotube network and paraffin wax with high affinity results in
      enhanced phase change enthalpy and thermal conductivity compared to pure paraffin
      wax. Our phase change composite can store energy in practical ways such as by
      sunlight absorption or under voltages applied by conventional lithium-ion
      batteries.

PMID- 23157569
TI  - Thermal dehydration of magnesium acetate tetrahydrate: formation and in situ
      crystallization of anhydrous glass.
AB  - The kinetics and mechanism of the thermal dehydration of magnesium acetate
      tetrahydrate were investigated as a typical example of the glass formation
      process via the thermal decomposition of solids. Formation of an intermediate
      fluid phase was identified as the characteristic phenomenon responsible for the
      formation of anhydrous glass. Thermal dehydration from the surface fluid layer
      regulates the zero-order-like rate behavior of the mass-loss process with an
      apparent activation energy E(a) ~ 70-80 kJ mol(-1). Because of variations in the
      mechanism of release of the water vapor with changes in the reaction temperature
      range, the mass-loss behavior is largely dependent on the particle size of the
      sample and heating conditions. The formation of hollow anhydrous glass is the
      novel finding of the present study. The mechanism of formation is discussed in
      terms of complementary interpretations of the morphological changes and kinetic
      behavior of the thermal dehydration. On further heating, the as-produced
      anhydrous glass exhibits a glass transition phenomenon at approximately 470 K
      with an E(a) ~ 550-560 kJ mol(-1), and subsequently crystallizes via the three
      dimensional growth of nuclei controlled by diffusion. The crystallization process
      is characterized by an E(a) ~ 280 kJ mol(-1) and an enthalpy change DeltaH = 
      13.3 kJ mol(-1), resulting in the formation of smaller, rounded particles of
      crystalline anhydrate.

PMID- 23157568
TI  - New perspectives for natural antimicrobial peptides: application as
      antinflammatory drugs in a murine model.
AB  - BACKGROUND: Antimicrobial peptides (AMPs) are an ancient group of defense
      molecules. AMPs are widely distributed in nature (being present in mammals,
      birds, amphibians, insects, plants, and microorganisms). They display
      bactericidal as well as immunomodulatory properties. The aim of this study was to
      investigate the antimicrobial and anti-inflammatory activities of a combination
      of two AMPs (temporin B and the royal jellein I) against Staphylococcus
      epidermidis. RESULTS: The temporin B (TB-KK) and the royal jelleins I, II, III
      chemically modified at the C terminal (RJI-C, RJII-C, RJIII-C), were tested for
      their activity against 10 different Staphylococcus epidermidis strains, alone and
      in combination. Of the three royal jelleins, RJI-C showed the highest activity.
      Moreover, the combination of RJI-C and TB-KK (MIX) displayed synergistic
      activity. In vitro, the MIX displayed low hemolytic activity, no NO2- production
      and the ability to curb the synthesis of the pro-inflammatory cytokines TNF-alpha
      and IFN-gamma to the same extent as acetylsalicylic acid. In vivo, the MIX
      sterilized mice infected with Staphylococcus epidermidis in eleven days and
      inhibited the expression of genes encoding the prostaglandin-endoperoxide
      synthase 2 (COX-2) and CD64, two important parameters of inflammation.
      CONCLUSION: The study shows that the MIX - a combination of two naturally
      occurring peptides - displays both antimicrobial and anti-inflammatory
      activities.

PMID- 23157570
TI  - Fate of deoxynivalenol, T-2 and HT-2 toxins and their glucoside conjugates from
      flour to bread: an investigation by high-performance liquid chromatography high
      resolution mass spectrometry.
AB  - Deoxynivalenol, T-2 and HT-2 toxins are mycotoxins frequently occurring in
      cereals and cereal-based products along with their conjugated forms. In this
      paper, we provide insights into the fate of deoxynivalenol, T-2 and HT-2 toxins
      and their glucoside derivatives during bread making, using naturally contaminated
      wheat flour. High-resolution mass spectrometry was used to assess the extent of
      degradation of the three mycotoxins during bread baking and to identify some
      glucoside conjugates, namely deoxynivalenol, T-2 and HT-2 mono-glucosides,
      detected both in the flour and in the respective breads. Our findings show
      deoxynivalenol's levels markedly increased upon baking, whereas those of HT-2 and
      T-2 toxins were decreased in the final bread with special regard to the T-2
      toxin.

PMID- 23157571
TI  - Atrial arrhythmogenesis in catecholaminergic polymorphic ventricular tachycardia-
      is there a mechanistic link between sarcoplasmic reticulum Ca(2+) leak and re
      entry?

PMID- 23157572
TI  - Variation in carbon availability, defense chemistry and susceptibility to fungal
      invasion along the stems of mature trees.
AB  - If carbon (C) sinks withdraw carbohydrates as they are transported along tree
      stems, carbohydrate availability may depend on local sink strength and distance
      from sources. Defenses, including monoterpenes--a major component of resin--limit
      the invasibility of pines. Since carbohydrate reserves fund monoterpene
      synthesis, we hypothesized that monoterpene concentrations in pine stems would
      decrease from the crown to the lower stem, and susceptibility to fungal infection
      would increase. Here, we measured carbohydrate and monoterpene concentrations
      along the stems of lodgepole pine trees (Pinus contorta var. latifolia) before
      inoculating with a blue-stain fungus at different heights. After 6 wk, we
      assessed tree responses to fungal infection based on lesion length and
      carbohydrate mobilization. Concentrations of carbohydrates and monoterpenes in
      the phloem before inoculation decreased with distance from the crown, whereas
      lesion lengths after inoculation increased. However, trees mobilized sugars in
      response to fungal infection such that carbohydrate reserves near lesions were
      similar at all heights. Despite C mobilization, the lower stem was more
      vulnerable than the upper stem. Consistent with predictions based on sink-source
      relationships, vulnerability occurred where carbohydrates were less available,
      and likely resulted from C withdrawal by sinks higher in the supply chain.

PMID- 23157573
TI  - Optogenetic control of cell function using engineered photoreceptors.
AB  - Over the past decades, there has been growing recognition that light can provide
      a powerful stimulus for biological interrogation. Light-actuated tools allow
      manipulation of molecular events with ultra-fine spatial and fast temporal
      resolution, as light can be rapidly delivered and focused with sub-micrometre
      precision within cells. While light-actuated chemicals such as photolabile
      'caged' compounds have been in existence for decades, the use of genetically
      encoded natural photoreceptors for optical control of biological processes has
      recently emerged as a powerful new approach with several advantages over
      traditional methods. Here, we review recent advances using light to control basic
      cellular functions and discuss the engineering challenges that lie ahead for
      improving and expanding the ever-growing optogenetic toolkit.

PMID- 23157574
TI  - Classification of stillbirths and risk factors by cause of death--a case-control
      study.
AB  - OBJECTIVE: To investigate risk factors for stillbirths by cause, using the Causes
      of Death and Associated Conditions (CODAC) classification system for perinatal
      deaths. DESIGN: Case-control study. SETTING: Two university hospitals in Oslo,
      Norway, January 1990 through December 2003. SAMPLE: Women with stillbirth after
      22 gestational weeks (n = 377) and controls with live births (n = 1 215), and a
      subsample of 105 cases and 262 controls. METHODS: Socio-demographic, clinical and
      thrombophilic risk factors for stillbirths were assessed by cause of death in
      univariate and multivariable logistic regression analyses. Stillbirths were
      classified according to CODAC based on information from medical records and
      validated placenta histology. MAIN OUTCOME MEASURES: Causes of stillbirths in
      percentages, prevalence, odds ratios and adjusted odds ratios for potential risk
      factors. RESULTS: Approximately half of the women (n = 190) had placental and
      19.4% (n = 73) unknown cause of stillbirth. Placental-associated conditions were
      registered in 18% (n = 68) of cases with a non-placental or an unknown cause.
      Smoking and small-for-gestational age were more prevalent in all causal groups,
      compared with controls, whereas twin pregnancy, hypertension and diabetes were
      more prevalent only among women with placental and unknown causes of stillbirth.
      The F2rs179963 polymorphism and combined thrombophilia were significant risk
      factors for stillbirth with placental causes and antiphospholipid antibodies for
      stillbirth with non-placental causes. CONCLUSIONS: Two-thirds of all stillbirths
      (68%) were caused by or associated with placental pathology. Risk factors
      differed somewhat according to cause, apart from smoking and small-for
      gestational age, which were significant risk factors across the causal groups.

PMID- 23157575
TI  - Patterns of hand preference and unintentional injuries among Indian attempted
      hand switchers and hand non-switchers.
AB  - This study examines the patterns of hand preference and unintentional injuries of
      attempted hand switchers and hand non-switchers. Data were collected from 3698
      participants in Kharagpur, India, on measures of hand preference, hand switching,
      and unintentional injuries. The direction of left- or right-handedness was on the
      basis of hand used for the item "writing on paper" and the degree of handedness
      was based on the average score of remaining items in the handedness inventory.
      Results reveal that, among attempted hand-switchers, learned right-handers were
      not right-sided in hand continuum as the natural right-handers, but left-handers
      were left-sided as natural left-handers. With increasing age the learned right
      handers become less right-sided and natural right-handers become more right
      sided. Females (males) are found to be more right-handed than males (females)
      among learned right-handers (natural right-handers). On the direction of
      handedness, the learned right-handers have more than twice the risk of
      unintentional injuries than the natural right- and left-handers. On degree of
      handedness, the use of inconsistent left and both hands among natural left
      handers, the use of inconsistent right and both hands among natural right
      handers, and the use of weak right hand among learned right-handers increase
      their vulnerability to unintentional injuries. Any deviation from the genetic
      make-up in hand use elevates the risk of unintentional injuries, suggesting that
      one should not change the biological hand. 

PMID- 23157576
TI  - Strippable coatings for forensic collection of trace chemicals from surfaces.
AB  - Surface sampling for chemical analysis plays a vital role in applications like
      environmental monitoring, industrial hygiene, homeland security, and forensics.
      The standard surface sampling tool is a simple cotton gauze pad, but as
      techniques become more sensitive and the variety of analytes increases, gauze is
      failing to meet the needs of the community. Here, the collection of eight small
      molecules from glass surfaces with three different commercial spray-on,
      strippable coatings was demonstrated and their collection efficiency, as measured
      by gas chromatography/mass spectrometry, was compared to that of a standard
      cotton gauze. The three coating systems recovered 87-95% of the each compound, on
      average, from a nominal initial surface coverage of 0.1 g/m(2) per analyte. These
      recoveries were 3-fold better than the cotton gauze which had an average
      collection efficiency of 31%.

PMID- 23157577
TI  - Validation of the volumetric measurement of a simulated maxillary alveolar bone
      defect using cone-beam computed tomography.
AB  - Objective : To determine the accuracy of volumetric measurement of a simulated
      alveolar bone defect using cone-beam computed tomography (CBCT) scans. Design :
      Laboratory-based observational study. Setting : University dental teaching
      hospital. Methods : Scans of a dried skull with an artificially created maxillary
      bone defect. Main Outcome Measures : The skull was scanned using an i-CAT CBCT
      scanner (Imaging Sciences International, Hatfield, PA) at 0.2 mm resolution. The
      superior and inferior aspects of the void were identified, and the volume was
      calculated by three-dimensional (3D) computational analysis of the CBCT scan
      using an algorithm created with MATLAB software (The Mathworks Inc., R2009a,
      Natick, MA). The skull was then scanned using micro computed tomography (micro
      CT) at 0.0934 mm resolution, and the volume of the defect was determined using
      the Studio Max 2.2 program (Volume Graphics, 2012, Heidelberg, Germany). The
      process was repeated two additional times, and the volumes were compared using a
      two-sample t test (P < .05). To determine the interobserver reproducibility of
      the identification of the superior and inferior aspects of the defect, the slices
      chosen to represent these extremities were selected by four separate observers
      and the data assessed using an F-test (P < .05). Results : The interobserver
      reproducibility of the identification of the superior and inferior boundaries of
      the defect was good (P = .18). The volumes computed from the i-CAT CBCT images
      were 4.11% lower than those computed from the micro-CT images; however, the
      difference was not statistically significant (P = .71). Conclusions : 3D
      volumetric measurement of simulated alveolar bone defects using i-CAT CBCT scans
      is similar to the volumes determined using micro-CT. 

PMID- 23157578
TI  - Emerged or imposed: a theory on the role of physical templates and self
      organisation for vegetation patchiness.
AB  - In this article, we develop a unifying framework for the understanding of spatial
      vegetation patterns in heterogeneous landscapes. While much recent research has
      focused on self-organised vegetation the prevailing view is still that biological
      patchiness is mostly due to top-down control by the physical landscape template,
      disturbances or predators. We suggest that vegetation patchiness in real
      landscapes is controlled both by the physical template and by self-organisation
      simultaneously, and introduce a conceptual model for the relative roles of the
      two mechanisms. The model considers four factors that control whether vegetation
      patchiness is emerged or imposed: soil patch size, plant size, resource input and
      resource availability. The last three factors determine the plant-patch size, and
      the plant-to-soil patch size ratio determines the impact of self-organisation,
      which becomes important when this ratio is sufficiently small. A field study and
      numerical simulations of a mathematical model support the conceptual model and
      give further insight by providing examples of self-organised and template
      controlled vegetation patterns co-occurring in the same landscape. We conclude
      that real landscapes are generally mixtures of template-induced and self
      organised patchiness. Patchiness variability increases due to source-sink
      resource relations, and decreases for species of larger patch sizes.

PMID- 23157579
TI  - Obesity, dyslipidemia and cholesterol gallstone disease during one year of
      Antarctic residence.
AB  - INTRODUCTION: Age, gender, ethnicity, geographic location, diet, obesity,
      diabetes mellitus and dyslipidemia are known risk factors for development of
      gallstone disease (GD). We describe the development of four cases of symptomatic
      GD including a case of acute cholecystitis in Indian Antarctic expedition members
      during 1 year of polar residence and their response to 6 months of
      ursodeoxycholic acid (UDCA) therapy. METHODS: Twenty subjects were evaluated at
      baseline and at serial intervals using clinical history, dietary assessment,
      anthropometry, blood investigations and ultrasonography for development of
      gallstone disease. Ursodeoxycholic acid and lipid lowering agents were prescribed
      as indicated and response to therapy measured over a period of 1 year in
      Antarctica. RESULTS: Four cases of cholesterol GD and two cases of biliary sludge
      were detected after 4 months. Dyslipidemia including hypertriglyceridemia in four
      of 20 cases (20%), hypercholesterolemia in nine of 20 cases (45%) and low high
      density lipoprotein (HDL) cholesterol in six of 20 cases (30%) was seen to
      develop after 3 months of polar residence. Impaired glucose tolerance was found
      in three of 20 cases (15%), two of whom developed gallstones. Ursodeoxycholic
      acid therapy completely dissolved gallstones in three cases and led to partial
      resolution in one case at 6 months. A trial of lipid lowering agents and 1 month
      of UDCA led to resolution of biliary sludge in both cases. CONCLUSION: Obesity,
      dyslipidemia, impaired glucose tolerance and high fat and caloric intake were
      found to increase the risk of developing cholesterol GD during the Antarctic
      expedition. Ursodeoxycholic acid therapy was found to be efficacious in
      dissolution of gallstones and prevention of formation of larger stones in cases
      with gall bladder sludge. The effect of geographical factors such as exposure to
      colder environments on the development of GD needs further research.

PMID- 23157580
TI  - Antigen 85A and mycobacterial DNA-binding protein 1 are targets of immunoglobulin
      G in individuals with past tuberculosis.
AB  - Development of accurate methods for predicting progression of tuberculosis (TB)
      from the latent state is recognized as vitally important in controlling TB,
      because a majority of cases develop from latent infections. Past TB that has
      never been treated has a higher risk of progressing than does latent
      Mycobacterium tuberculosis infection in patients who have previously received
      treatment. Antibody responses against 23 kinds of M. tuberculosis proteins in
      individuals with past TB who had not been medicated were evaluated. These
      individuals had significantly higher concentrations of antibodies against Antigen
      85A and mycobacterial DNA-binding protein 1 (MDP1) than did those with active TB
      and uninfected controls. In addition, immunohistochemistry revealed
      colocalization of tubercle bacilli, antigen 85 and MDP1 inside tuberculous
      granuloma lesions in an asymptomatic subject, showing that M. tuberculosis in
      lesions expresses both antigen 85 and MDP1. Our study suggests the potential
      usefulness of measuring antibody responses to antigen 85A and MDP1 for assessing
      the risk of TB progression.

PMID- 23157581
TI  - Pharmacokinetics and safety of adjunctive topiramate in infants (1-24 months)
      with refractory partial-onset seizures: a randomized, multicenter, open-label
      phase 1 study.
AB  - PURPOSE: To characterize the pharmacokinetics of adjunctive topiramate in infants
      (1-24 months) with refractory partial-onset seizures (POS); also to evaluate
      safety and tolerability of topiramate in the dose range of 3-25 mg/kg/day.
      METHODS: In this open-label phase 1 study, infants (N = 55) with refractory POS
      receiving at least one concurrent antiepileptic drug (AED) were enrolled. Infants
      were stratified by age and randomly assigned to one of four topiramate target
      dose groups (3-, 5-, 15-, or 25 mg/kg/day). Treatment was initiated at 3
      mg/kg/day with titration to the target dose by weekly dose escalation. Topiramate
      was administered daily in two divided doses as oral liquid (5 mg/ml for infants
      <9 kg or those who could not tolerate solid foods) or sprinkle capsule (25 mg)
      formulations. Following seven consecutive days of topiramate administration at
      the target dose, four blood samples were collected from each infant for
      pharmacokinetic assessments (predose, 1-3, 4-6, and 8-10 h postdose). KEY
      FINDINGS: Fifty-five infants (mean [SD] age in months: 11.4 [5.79]) with POS were
      enrolled, of whom 33% had seizures with or without secondary generalization.
      Complete pharmacokinetic profiles were obtained in 35 infants in whom mean plasma
      topiramate concentration-time profiles demonstrated linear pharmacokinetics
      (predose topiramate concentrations [C(trough) ] and area under the plasma
      concentration-time curve from time 0 through 12 h [AUC(12 h)]) of topiramate over
      the dose range studied). Apparent steady state oral clearance (CL(ss) /F)
      remained similar across all topiramate target dose groups and was independent of
      creatinine clearance, age, and weight. Mean values for CL(ss) /F were
      approximately twofold greater in infants receiving concomitant enzyme-inducing
      AEDs versus enzyme-inhibiting AEDs. Topiramate was well tolerated and safety
      findings were consistent with previous reports in children and adults. Most
      common treatment emergent adverse events (>=10%) were upper respiratory tract
      infection, fever, vomiting, somnolence, and anorexia. SIGNIFICANCE: In infants (1
      24 months), topiramate exhibited linear steady state pharmacokinetics over the
      dose range 3-25 mg/kg/day, and CL(ss) /F of topiramate was independent of dose.
      Moreover, the concomitant enzyme-inducing AEDs doubled the clearance of
      topiramate. Topiramate was generally well tolerated as adjunctive therapy at
      doses up to 25 mg/kg/day.

PMID- 23157582
TI  - Cell adhesion on a POEGMA-modified topographical surface.
AB  - It is well known that adsorbed proteins play a major role in cell adhesion.
      However, it has also been reported that cells can adhere to a protein-resistant
      surface. In this work, the behavior of L02 and BEL-7402 cells on a protein
      resistant, 3D topographical surface was investigated. The topographical gold
      nanoparticle layer (GNPL) surfaces were prepared by chemical gold plating, and
      the topography was described by roughness parameters acquired from a multiscale
      analysis. Both smooth Au and GNPL surfaces were modified with POEGMA polymer
      brushes using surface-initiated ATRP. The dry and hydrated thicknesses of POEGMA
      brushes on both smooth and rough surfaces were measured by AFM using a
      nanoindentation method. Protein adsorption experiments using (125)I radiolabeling
      revealed similarly low levels of protein adsorption on smooth and GNPL surfaces
      modified with POEGMA, thus allowing an investigation of the effects of topography
      on cell behavior under conditions of minimal protein adsorption. The roles of VN
      and FN adsorption in both L02 cells and BEL-7402 cells adhesion were investigated
      using cell culturing with and without a serum supplement. It was found that
      initial cell adhesion occurred via proteins adsorbed from the cell culture
      medium, whereas subsequent durable cell adhesion could be attributed to the
      topographical structure of the surface. Although cell spreading on protein
      resistant surfaces was constrained because of the lack of adsorbed proteins, we
      found that cells adherent to topographical surfaces were more firmly attached and
      thus were more durable compared to those on smooth surfaces. In general, however,
      we conclude that topography is more important for cell adhesion on a protein
      resistant surface.

PMID- 23157583
TI  - Potential toxicity of caffeine when used as a dietary supplement for weight loss.
AB  - Many dietary supplements being promoted for weight loss contain caffeine- or
      ephedra-related alkaloids to increase energy and suppress appetite. People may be
      unaware that supplements can contain caffeine, even if caffeine is not listed as
      an ingredient. Commonly used herbal dietary supplement ingredients, such as
      guarana, are natural sources of caffeine. Additions of these natural sources of
      caffeine to dietary supplements have increased in recent years. We describe a
      case of possible caffeine-induced seizure in a patient taking an over-the-counter
      weight loss supplement. A previously healthy 38-year-old female experienced
      blurring of vision and a new onset grand mal seizure. The patient had a 2-month
      history of taking the dietary supplement, Zantrex-3TM. Zantrex-3TM is advertised
      as a weight loss supplement, which may provide rapid weight loss and extreme
      energy in one "power packed pill." Zantrex-3TM is a proprietary blend containing
      niacin, caffeine, and various herbs. After presenting to the hospital emergency
      room, the patient's chemistry panel, with the exception of potassium (2.9 mEq/L),
      was within normal limits. An electroencephalogram (EEG) was unremarkable. The
      magnetic resonance imaging (MRI) showed possible atrophy in the right frontal
      lobe. Findings from follow-up MRI and EEG ordered as an outpatient were within
      normal limits. After discontinuation of Zantrex-3TM, the patient has experienced
      no further seizure activity.

PMID- 23157584
TI  - An evidence-based systematic review of vitamin A by the natural standard research
      collaboration.
AB  - An evidence-based systematic review of vitamin A by the Natural Standard Research
      Collaboration consolidates the safety and efficacy data available in the
      scientific literature using a validated and reproducible grading rationale. This
      paper includes written and statistical analysis of clinical trials, plus a
      compilation of expert opinion, folkloric precedent, history, pharmacology,
      kinetics/dynamics, interactions, adverse effects, toxicology, and dosing.

PMID- 23157585
TI  - An effective vaccination approach augments anti-HIV systemic and vaginal immunity
      in mice with decreased HIV-1 susceptible alpha4beta7high CD4+ T cells.
AB  - HIV-1 preferentially infects activated CD4(+) T cells expressing alpha4beta7
      integrin and conventional vaccination approaches non-selectively induce immune
      responses including alpha4beta7(high) CD4(+) T cells, suggesting that current
      candidate AIDS vaccines may produce more target cells for HIV-1 and paradoxically
      enhance HIV-1 infection. Thus it remains a challenge to selectively induce robust
      anti-HIV immunity without the unwanted HIV-1 susceptible alpha4beta77(high)
      CD4(+)+ T cells. Here we describe a vaccination strategy that targets ALDH1a2, a
      retinoic acid producing enzyme in dendritic cells (DCs). Silencing ALDH1a2 in DCs
      enhanced the maturation and production of proinflammatory cytokines of DCs and
      promoted Th1/Th2 differentiation while suppressing Treg. ALDH1a2-silenced DCs
      effectively downregulated the expression of guthoming receptors alpha4beta77 and
      CCR9 on activated T and B lymphocytes. Consequently, intranasal immunization of a
      lentiviral vaccine encoding ALDH1a2 shRNA and HIV-1 gp140 redirected gp140
      specific mucosal T cell and antibody responses from the gut to the vaginal tract,
      while dramatically enhancing systemic gp140-specific immune responses. We further
      demonstrated that silencing ALDH1a2 in human DCs resulted in downregulation of
      beta7 expression on activated autologous CD4(+) T cells. Hence this study
      provides a unique and effective strategy to induce alpha4beta7(low) anti-HIV
      immune responses.

PMID- 23157587
TI  - HIV-1 X4 activities of polycationic "viologen" based dendrimers by interaction
      with the chemokine receptor CXCR4: study of structure-activity relationship.
AB  - A series of "viologen" based dendrimers with polycationic scaffold carrying 10,
      18, 26, 42, and 90 charges per molecule were used to determine the structure
      activity relationship (SAR) with regard to HIV-1 inhibitory activity. The studies
      involved five compounds with a high activity against HIV-1 already utilized in
      our previous study (1)  and five new dendrimers. Such dendrimers block HIV-1
      entry into the cell, indicating that they bind to HIV-1 surface proteins and/or
      on the host cell receptors required for entry. The increasing positive character
      of dendrimers leads to more cytotoxicity. The 10 charges dendrimers (1, 6) have
      less influence on the cell viability but low inhibition of the binding of the
      CXCR4 mAb clone 1D9. Thus, dendrimers with 18 charges (2, 7) are the most
      promising CXCR4 imaging probes. We report the design, synthesis, and biological
      activity of new HIV-1 inhibitors that are conceptually distinct from those of the
      existing HIV-1 inhibitors.

PMID- 23157586
TI  - Nutritional factors and gender influence age-related DNA methylation in the human
      rectal mucosa.
AB  - Aberrant methylation of CpG islands (CGI) occurs in many genes expressed in
      colonic epithelial cells, and may contribute to the dysregulation of signalling
      pathways associated with carcinogenesis. This cross-sectional study assessed the
      relative importance of age, nutritional exposures and other environmental factors
      in the development of CGI methylation. Rectal biopsies were obtained from 185
      individuals (84 male, 101 female) shown to be free of colorectal disease, and for
      whom measurements of age, body size, nutritional status and blood cell counts
      were available. We used quantitative DNA methylation analysis combined with
      multivariate modelling to investigate the relationships between nutritional,
      anthropometric and metabolic factors and the CGI methylation of 11 genes,
      together with LINE-1 as an index of global DNA methylation. Age was a consistent
      predictor of CGI methylation for 9/11 genes but significant positive associations
      with folate status and negative associations with vitamin D and selenium status
      were also identified for several genes. There was evidence for positive
      associations with blood monocyte levels and anthropometric factors for some
      genes. In general, CGI methylation was higher in males than in females and
      differential effects of age and other factors on methylation in males and females
      were identified. In conclusion, levels of age-related CGI methylation in the
      healthy human rectal mucosa are influenced by gender, the availability of folate,
      vitamin D and selenium, and perhaps by factors related to systemic inflammation.

PMID- 23157588
TI  - Editorial comment to Pathophysiology of urinary incontinence in murine models.

PMID- 23157589
TI  - Holding onto electrons in alkali metal halide clusters: decreasing polarizability
      with increasing coordination.
AB  - The connection between the electronic polarizability and the decrease of the
      system size from macroscopic solid to nanoscale clusters has been addressed in a
      combined experimental and model-calculation study. A beam of free neutral
      potassium chloride clusters has been probed using synchrotron-radiation-based
      photoelectron spectroscopy. The introduction of "effective" polarizability for
      chlorine, lower than that in molecules and dimers and decreasing with increasing
      coordination, has allowed us to significantly improve the agreement between the
      experimental electron binding energies and the electrostatic model predictions.
      Using the calculated site-specific binding energies, we have been able to assign
      the spectral details of the cluster response to the ionizing X-ray radiation, and
      to explain its change with cluster size. From our assignments we find that the
      higher-coordination face-atom responses in the K 3p spectra increase
      significantly with increasing cluster size relative to that of the edge atoms.
      The reasons behind the decrease of polarizability predicted earlier by ab initio
      calculations are discussed in terms of the limited mobility of the electron
      clouds caused by the interaction with the neighboring ions.

PMID- 23157590
TI  - Synthesis and biological evaluation of novel antifolate analogs as potential
      anticancer treatment.
AB  - A novel process for the preparation of two ketomethylenic antifolates, 2-(2-{4
      [(2,4-diamino-pteridin-6-ylmethyl)-amino]- phenyl}-2-oxo-ethyl) pentanedioic acid
      and 2-(2-{4-[(2,4-diamino-pteridin-6-ylmethyl)-methyl-amino]-phenyl}-2-oxo-ethyl)
      pentanedioic acid is described herein. Both compounds were compared with
      methotrexate as inhibitors of human dihydrofolate reductase and thymidylate
      synthase. The in-vitro and in-vivo results suggest that these novel antifolate
      inhibitors could potentially constitute effective therapeutic molecules in the
      treatment of certain cancers and might present a lower toxicity profile than
      methotrexate.

PMID- 23157591
TI  - Inhibition of PCAF by anacardic acid derivative leads to apoptosis and breaks
      resistance to DNA damage in BCR-ABL-expressing cells.
AB  - Acetylation of histones and nonhistone proteins is a posttranslational
      modification which plays a major role in the regulation of intracellular
      processes involved in tumorigenesis. It was shown that different acetylation of
      proteins correlates with development of leukemia. It is proposed that histone
      acetyltransferases (HATs) are important novel drug targets for leukemia
      treatment, however data are still not consistent. Our previous data showed that a
      derivative of anacardic acid - small molecule MG153, which has been designed and
      synthesized to optimize the HAT inhibitory potency of anacardic acid, is a potent
      inhibitor of p300/CBP associated factor (PCAF) acetyltransferase. Here we ask
      whether inhibition of PCAF acetyltransferase with MG153 will show proapoptotic
      effects in cells expressing BCR-ABL, which show increased PCAF expression and are
      resistant to apoptosis. We found that inhibition of PCAF decreases proliferation
      and induces apoptosis, which correlates with loss of the mitochondrial membrane
      potential and DNA fragmentation. Importantly, cells expressing BCR-ABL are more
      sensitive to PCAF inhibition compared to parental cells without BCRABL. Moreover,
      inhibition of PCAF in BCR-ABL-expressing cells breaks their resistance to DNA
      damage-induced cell death. These findings provide direct evidence that targeting
      the PCAF alone or in combination with DNA-damaging drugs shows cytotoxic effects
      and should be considered as a prospective therapeutic strategy in chronic myeloid
      leukemia cells. Moreover, we propose that anacardic acid derivative MG153 is a
      valuable agent and further studies validating its therapeutic relevance should be
      performed.

PMID- 23157592
TI  - Antiproliferative activities on renal, prostate and melanoma cancer cell lines of
      Sarcopoterium spinosum aerial parts and its major constituent tormentic acid.
AB  - The search for improved cytotoxic agents continues to be an important line in the
      discovery of modern anticancer drugs. Sarcopoterium spinosum (L.) Spach is
      mentioned in ethnobotanical surveys as a medicinal plant used for the treatment
      of cancer. The aim of this study is to investigate and to compare the aerial
      parts of S. spinosum collected in Italy and Lebanon for their chemical
      composition and their antiproliferative activity against ACHN, C32, A375, MCF-7,
      LNCaP and HeLa human cancer cell lines using SRB assay. The main constituent
      tormentic acid was isolated by MPLC and characterized by spectroscopic techniques
      (NMR, MS). Non polar compounds were analyzed by GC and GC-MS. S. spinosum showed
      an interesting antiproliferative activity against ACHN and C32 cell lines with
      IC(50) values of 2.4 and 2.7 MUg/ml for S. spinosum from Italy and Lebanon,
      respectively. Remarkable results were obtained also against A375 and LNCaP cell
      lines. The cytotoxicity against ACHN cell line could be partially attributed to
      tormentic acid that demonstrated a higher cytotoxicity than the positive control
      vinblastine. Close association between the radical scavenging activity (evaluated
      by DPPH and ABTS assay) and cytotoxicity was also demonstrated. This
      investigation demonstrated the potential cytotoxic activity of S. spinosum taking
      into account also that none of the tested extracts, fractions and isolated
      compound affected the proliferation of normal cell line 142BR. Tormentic acid,
      the major constituent isolated from S. spinosum, play an important role in the
      cytotoxicity exhibited by the extract.

PMID- 23157593
TI  - NF-kappaB down-regulation and PARP cleavage by novel 3-alpha-butyryloxy-beta
      boswellic acid results in cancer cell specific apoptosis and in vivo tumor
      regression.
AB  - The present study relates to the induction of apoptosis thereof cytotoxicity and
      anti-cancer activity displayed by semi-synthetic analog of Boswellic acid i.e. 3
      alpha-Butyryloxy-beta-boswellic acid (BOBA). The cytotoxicity data revealed the
      differential sensitivity of cancer cell lines towards BOBA which may display its
      impact against different types of cancers. Considering the inhibitory potential
      of BOBA, we further sought to understand the target for BOBA deciphering the
      mechanism of action leading to apoptotic cell death and it was for the first time
      reported about the triterpenoid ring especially the beta-boswellic acid
      derivative is targeting PI3K pathway. Our data revealed that BOBA treatment
      provides evidence about the apoptotic nature showing the potential of targeting
      mitochondria dependent pathways during apoptosis in HL-60 cells. BOBA induced
      hypo-diploid sub-G(1) DNA population in HL-60 cells as was also evident from the
      pattern of DNA fragmentation and mitochondrial membrane potential (LambdaPsim)
      loss. Morphological analysis under fluorescent and scanning electron microscopy
      displayed typical features such as cell shrinkage, membrane blebbing, chromatin
      condensation and nuclear fragmentation. These events paralleled with the down
      regulation of NF-kappaB and induced PARP cleavage. Furthermore, it is noteworthy
      that BOBA also depicted significant growth inhibition in Ehrlich Ascitic Tumour
      (EAT), Ehrlich Ascitic Carcinoma (EAC) and Sarcoma- 180 tumour models. Taken
      together, BOBA treatment may represent as potential agent to the currently
      available anticancer agents in both prophylactic and/or therapeutic applications.
      Also, our findings may open up a new perspective in the construction of novel
      anticancer agents based on boswellic acids that will facilitate the development
      of these agents for anticancer therapeutics.

PMID- 23157594
TI  - Cucurmosin kills human pancreatic cancer SW-1990 cells in vitro and in vivo.
AB  - OBJECTIVE: To investigate the effect of cucurmosin (CUS) on proliferation
      inhibition in the human pancreatic cancer cell line SW-1990 in vitro and in vivo.
      METHODS: 1. MTT assay was used to analyse the proliferation inhibition of CUS in
      SW-1990 cells compared with gemcitabine (GEM) in vitro. 2. We established an NOD
      SCID mice orthotopic transplantation model and estimated the proliferation
      inhibition effect of CUS in SW-1990 cells in vivo. 3. Western blot was used to
      determine the protein expressions of Caspase 3, Bcl-2, Caspase 9, PI3K, Akt,
      mTOR, P70S6k, and 4E-BP1 after CUS intervention. RESULTS: 1. CUS inhibited the
      proliferation of pancreatic cancer cells and induced apoptosis in CUS dose- and
      time-dependent manners. 2. NOD-SCID mice models were established successfully,
      and the tumour proliferation inhibition rates of these models increased compared
      with the control group. 3. CUS inhibited all of the examined proteins in the
      PI3K/Akt/mTOR signalling pathway and induced active fragments of Caspase 3 and
      Caspase 9. CONCLUSION: 1. CUS can inhibit the growth of SW-1990 cells in vitro
      and in vivo. 2. CUS can induce apoptosis in SW-1990 cells to inhibit cell growth.

PMID- 23157595
TI  - Ultralow-threshold two-photon pumped amplified spontaneous emission and lasing
      from seeded CdSe/CdS nanorod heterostructures.
AB  - Ultralow-threshold two-photon pumped amplified spontaneous emission (2ASE) and
      lasing in seeded CdSe/CdS nanodot/nanorod heterostructures is demonstrated for
      the first time. Such heterostructures allow the independent tunability of the two
      photon absorption (2PA) cross-section (sigma(2)) through varying the CdS rod
      size, and that of the emission wavelength through varying the CdSe dot size. With
      an enhanced sigma(2), 2ASE in these heterostructures is achieved with an ultralow
      threshold fluence of ~1.5 mJ/cm(2), which is as much as one order less than that
      required for spherical semiconductor NCs. Importantly, by exploiting this unique
      property of the seeded nanorods exhibiting strong quantum confinement even at
      relatively large rod sizes, a near reciprocal relation between the 2ASE threshold
      and the 2PA action cross-section (sigma(2)eta) (where eta is the quantum yield)
      was found and validated over a wide volume range for II-VI semiconductor
      nanostructures. Ultrafast optical spectroscopy verified that while the Auger
      processes in these heterostructures are indeed suppressed, ASE in these samples
      could also be strongly affected by a fast hole-trapping process to the NR surface
      states. Lastly, to exemplify the potential of these seeded CdSe/CdS
      nanodot/nanorod heterostructures as a viable gain media for achieving two-photon
      lasing, a highly photostable microsphere laser with an ultralow pump threshold is
      showcased.

PMID- 23157596
TI  - PHB granules are attached to the nucleoid via PhaM in Ralstonia eutropha.
AB  - BACKGROUND: Poly(3-hydroxybutyrate) (PHB) granules are important storage
      compounds of carbon and energy in many prokaryotes which allow survival of the
      cells in the absence of suitable carbon sources. Formation and subcellular
      localization of PHB granules was previously assumed to occur randomly in the
      cytoplasm of PHB accumulating bacteria. However, contradictionary results on
      subcellular localization of PHB granules in Ralstonia eutropha were published,
      recently. RESULTS: Here, we provide evidence by transmission electron microscopy
      that PHB granules are localized in close contact to the nucleoid region in R.
      eutropha during growth on nutrient broth. Binding of PHB granules to the nucleoid
      is mediated by PhaM, a PHB granule associated protein with phasin-like properties
      that is also able to bind to DNA and to phasin PhaP5. Over-expression of PhaM
      resulted in formation of many small PHB granules that were always attached to the
      nucleoid region. In contrast, PHB granules of ?phaM strains became very large and
      distribution of granules to daughter cells was impaired. Association of PHB
      granules to the nucleoid region was prevented by over-expression of PhaP5 and
      clusters of several PHB granules were mainly localized near the cell poles.
      CONCLUSION: Subcellular localization of PHB granules is controlled in R. eutropha
      and depends on the presence and concentrations of at least two PHB granule
      associated proteins, PhaM and PhaP5.

PMID- 23157597
TI  - Contamination of barley seeds with Fusarium species and their toxins in Spain: an
      integrated approach.
AB  - Fusarium is a globally distributed fungal genus that includes different species
      pathogenic to cereals among others crops. Some of these Fusarium species can also
      produce toxic compounds towards animals and humans. In this work, the presence of
      the most important Fusarium toxins was determined in barley seeds from Spain,
      sampled according to European Union requirements. The results obtained were
      compared with the presence of mycotoxigenic species considered responsible for
      their synthesis by using species-specific polymerase chain reaction protocols.
      Fumonisins B(1) and B(2), zearalenone, trichothecenes type A (T-2 and HT-2) and
      trichothecenes type B (deoxynivalenol and nivalenol) were analysed by using high
      performance liquid chromatography. Deoxynivalenol and zearalenone were detected
      in 72% and 38% of the barley samples, respectively, at levels below European
      Union limits in all cases. However, the co-occurrence of both toxins in 34% of
      the samples suggested that synergistic activity of these two mycotoxins should be
      evaluated. Nivalenol and HT-2/T-2 were detected at low levels in 17% and 10% of
      the samples, respectively. Fumonisins occurred in 34% of the samples at levels up
      to 300 ug/kg. This suggested that they might represent a risk in Spanish barley,
      and to our knowledge, this is the first report on the presence of fumonisins in
      barley in this country. The species-specific polymerase chain reaction assays to
      detect mycotoxin-producing Fusarium species showed a very consistent correlation
      between F. verticillioides detection and fumonisin contamination as well as F.
      graminearum presence and zearalenone, deoxynivalenol and nivalenol contamination
      in barley samples. The approach used in this study provided information of
      mycotoxin contamination of barley together with the identification of the fungal
      species responsible for their production. Detection of the species with the
      current polymerase chain reaction assay strategy may be considered predictive of
      the potential mycotoxin risk in this matrix.

PMID- 23157598
TI  - Coexistence between native and exotic species is facilitated by asymmetries in
      competitive ability and susceptibility to herbivores.
AB  - Differences between native and exotic species in competitive ability and
      susceptibility to herbivores are hypothesized to facilitate coexistence. However,
      little fieldwork has been conducted to determine whether these differences are
      present in invaded communities. Here, we experimentally examined whether
      asymmetries exist between native and exotic plants in a community invaded for
      over 200 years and whether removing competitors or herbivores influences
      coexistence. We found that natives and exotics exhibit pronounced asymmetries, as
      exotics are competitively superior to natives, but are more significantly
      impacted by herbivores. We also found that herbivore removal mediated the outcome
      of competitive interactions and altered patterns of dominance across our field
      sites. Collectively, these findings suggest that asymmetric biotic interactions
      between native and exotic plants can help to facilitate coexistence in invaded
      communities.

PMID- 23157599
TI  - Simultaneous absolute determination of particle size and effective density of
      submicron colloids by disc centrifuge photosedimentometry.
AB  - Disc centrifuge photosedimentometry (DCP) with fluids of different densities is
      used to simultaneously determine the particle size and effective density of
      spherical silica particles. Incorporation of a calibrated infrared pyrometer into
      a DCP instrument is shown to enhance the measurement capability of the DCP
      technique by correcting for the temperature dependence of the spin fluid's
      density and viscosity. Advantages of absolute DCP determinations for size and
      density analysis relative to standardized DCP measurements include the
      elimination of instrument standardization with a particle of known density and
      measurements or estimation of the effective particle density. The reliability of
      diameter determinations provided by absolute DCP was confirmed using silica
      particles with nominal diameters ranging from 250 to 700 nm by comparison of
      these analyses with a diameter determination by transmission electron microscopy
      for silica particle size standards. Effective densities determined by absolute
      DCP for the silica particles ranged from 2.02 to 2.34 g/cm(3). These findings
      indicate that the silica particles have little or no porosity. The reported
      characterization of colloidal silica using absolute DCP suggests applicability of
      the technique to a variety of particle types including colloidal materials other
      than silica, core-shell particles, compositionally heterogeneous mixtures of
      nanoparticles, and irregularly shaped, structured colloids.

PMID- 23157600
TI  - The silent social/emotional signals in left and right cheek poses: a literature
      review.
AB  - When posing for a painted or photographic portrait, people are more likely to
      offer their left, rather than right, cheek (e.g., the Mona Lisa). Why? This paper
      reviews research investigating the left cheek bias, and the reasons underlying
      this posing asymmetry. Ruling out mechanical and perceptual biases, the paper
      focuses on the silent emotional and social signals conveyed by left and right
      cheek poses, demonstrating that people intuitively offer the left cheek to
      express emotion and perceive left cheek poses as more emotional. Moreover,
      because the left cheek appears more emotionally expressive, we unconsciously use
      cheek shown as a cue when presenting or determining academic specialisation,
      scientific standing, and even political affiliation. The research is consistent
      in suggesting that something as subtle as a 15 degrees  head turn implicitly
      influences others' perceptions: if you want to be perceived as open and creative,
      rather than dry and scientific, it might be time to turn the other cheek. 

PMID- 23157601
TI  - Update on rilpivirine: a new potent non-nucleoside reverse transcriptase
      inhibitor (NNRTI) of HIV replication.
AB  - INTRODUCTION: A combination of antiretroviral drugs (ARVs) is necessary to
      achieve sustained virologic suppression of HIV viral load (< 50 copies/mL).
      Rilpivirine (RPV) is a potent new non-nucleoside reverse transcriptase inhibitor
      (NNRTI) that has the potential to be part of effective ARV combinations. Here, we
      review currently available data on RPV from the standpoint of virologic
      suppression and efficacy, drug-drug interactions safety, and resistance. AREAS
      COVERED: This review presents data on the results of clinical trials involving
      RPV. The topics considered include antiviral potency, dosing, clinical utility,
      drug resistance, toxicity profile, and pharmacokinetics. EXPERT OPINION: RPV is a
      potent new addition to the antiretroviral family of drugs for use in combination
      therapy in previously untreated HIV-infected patients. However, caution needs to
      be exercised in administration of RPV to patients who initiated therapy with
      viral loads > 100,000 viral RNA copies/mL.

PMID- 23157602
TI  - Gd(DOTAla): a single amino acid Gd-complex as a modular tool for high relaxivity
      MR contrast agent development.
AB  - MR imaging at high magnetic fields benefits from an increased signal-to-noise
      ratio; however T(1)-based MR contrast agents show decreasing relaxivity (r(1)) at
      higher fields. High field, high relaxivity contrast agents can be designed by
      carefully controlling the rotational dynamics of the molecule. To this end, we
      investigated applications of the alanine analogue of Gd(DOTA), Gd(DOTAla). Fmoc
      protected DOTAla suitable for solid phase peptide synthesis was synthesized and
      integrated into polypeptide structures. Gd(III) coordination results in very
      rigid attachment of the metal chelate to the peptide backbone through both the
      amino acid side chain and coordination of the amide carbonyl. Linear and cyclic
      monomers (GdL1, GdC1), dimers (Gd(2)L2, Gd(2)C2), and trimers (Gd(3)L3, Gd(3)C3)
      were prepared and relaxivities were determined at different field strengths
      ranging from 0.47 to 11.7 T. Amide carbonyl coordination was indirectly confirmed
      by determination of the hydration number q for the EuL1 integrated into a peptide
      backbone, q = 0.96 +/- 0.09. The water residency time of GdL1 at 37  degrees C
      was optimal for relaxivity, tau(M) = 17 +/- 2 ns. Increased molecular size leads
      to increased per Gd relaxivity (from r(1) = 7.5 for GdL1 to 12.9 mM(-1) s(-1) for
      Gd(3)L3 at 1.4 T, 37  degrees C). The cyclic, multimeric derivatives exhibited
      slightly higher relaxivities than the corresponding linearized multimers
      (Gd(2)C2: r(1) = 10.5 mM(-1) s(-1) versus Gd(2)C2-red r(1) = 9 mM(-1) s(-1) at
      1.4 T, 37  degrees C). Overall, all six synthesized Gd complexes had higher
      relaxivities at low, intermediate, and high fields than the clinically used small
      molecule contrast agent [Gd(HP-DO3A)(H(2)O)].

PMID- 23157603
TI  - Pupil size varies with word listening and response selection difficulty in older
      adults with hearing loss.
AB  - Listening to speech in noise can be exhausting, especially for older adults with
      impaired hearing. Pupil dilation is thought to track the difficulty associated
      with listening to speech at various intelligibility levels for young and middle
      aged adults. This study examined changes in the pupil response with acoustic and
      lexical manipulations of difficulty in older adults with hearing loss.
      Participants identified words at two signal-to-noise ratios (SNRs) among options
      that could include a similar-sounding lexical competitor. Growth Curve Analyses
      revealed that the pupil response was affected by an SNR * Lexical competition
      interaction, such that it was larger and more delayed and sustained in the harder
      SNR condition, particularly in the presence of lexical competition. Pupillometry
      detected these effects for correct trials and across reaction times, suggesting
      it provides additional evidence of task difficulty than behavioral measures
      alone.

PMID- 23157604
TI  - Cerebral blood flow dynamics of orthostatic transient ischemic attacks in a
      patient with carotid dissection and fibromuscular dysplasia.
AB  - In patients with critical carotid stenosis and ischemic stroke, it is crucial to
      determine whether distal hypoperfusion or artery-to-artery embolism is the
      predominant mechanism. The role of transcranial doppler (TCD) in this setting is
      vital. We report a patient with fibromuscular dysplasia and recurrent orthostatic
      transient ischemic attacks where fall in cerebral perfusion was clearly
      demonstrated by TCD. 

PMID- 23157605
TI  - Inborn errors of creatine metabolism and epilepsy.
AB  - Creatine metabolism disorders include guanidinoacetate methyltransferase (GAMT)
      deficiency, arginine:glycine amidinotransferase (AGAT) deficiency, and the
      creatine transporter (CT1-encoded by SLC6A8 gene) deficiency. Epilepsy is one of
      the main symptoms in GAMT and CT1 deficiency, whereas the occurrence of febrile
      convulsions in infancy is a relatively common presenting symptom in all the three
      above-mentioned diseases. GAMT deficiency results in a severe early onset
      epileptic encephalopathy with development arrest, neurologic deterioration, drug
      resistant seizures, movement disorders, mental disability, and autistic-like
      behavior. In this disorder, epilepsy and associated abnormalities on
      electroencephalography (EEG) are more responsive to substitutive treatment with
      creatine monohydrate than to conventional antiepileptic drugs. AGAT deficiency is
      mainly characterized by mental retardation and severe language disorder without
      epilepsy. In CT1 deficiency epilepsy is generally less severe than in GAMT
      deficiency. All creatine disorders can be investigated through measurement of
      creatine metabolites in body fluids, brain proton magnetic resonance spectroscopy
      ((1) H-MRS), and molecular genetic techniques. Blood guanidinoacetic acid (GAA)
      assessment and brain H-MRS examination should be part of diagnostic workup for
      all patients presenting with epileptic encephalopathy of unknown origin. In girls
      with learning and/or intellectual disabilities with or without epilepsy, SLC6A8
      gene assessment should be part of the diagnostic procedures. The aims of this
      review are the following: (1) to describe the electroclinical features of
      epilepsy occurring in inborn errors of creatine metabolism; and (2) to delineate
      the metabolic alterations associated with GAMT, AGAT, and CT1 deficiency and the
      role of a substitutive therapeutic approach on their clinical and
      electroencephalographic epileptic patterns.

PMID- 23157606
TI  - Sequential urodynamic assessment before and after laparoscopic sacrocolpopexy.
AB  - OBJECTIVE: Controversial data are available as to whether to perform a
      simultaneous abdominal or vaginal colposuspension operation in laparoscopic
      sacrocolpopexy procedures. We wanted to evaluate the effect of a modified
      laparoscopic operation technique on urodynamic parameters and lower urinary tract
      symptoms. DESIGN: Prospective single center cohort study. SETTING: Teaching
      hospital. POPULATION: Forty-nine consecutive patients who underwent a modified
      laparoscopic sacrocolpopexy/hysteropexy operation using bone anchor fixation and
      synthetic mesh, performed by the same laparoscopic surgeons. METHODS: Pre- and
      postoperative multichannel urodynamic evaluation and validated questionnaires.
      The same urologist, blinded to the results of the questionnaire survey,
      interpreted all urodynamic evaluations. MAIN OUTCOME MEASURES: The effects of
      surgery on pelvic anatomy and patient satisfaction, urodynamic observations and
      diagnoses and symptom scores in validated questionnaires. RESULTS: Forty-two
      patients consented to pre- and postoperative urodynamic evaluation. Laparoscopic
      sacrocolpopexy successfully corrected vaginal vault prolapse in all 42 patients
      with urodynamic evaluation six months after surgery. The bladder volume at first
      desire to void was significantly increased and the maximal detrusor pressure at
      voiding phase was significantly decreased. In the questionnaires, irritative and
      storage voiding symptoms were significantly decreased. CONCLUSIONS: The results
      of the study demonstrate that there are no adverse urodynamic findings following
      this modified technique for laparoscopic sacrocolpopexy. The statistically
      significant urodynamic improvements are in accordance with the scores on the
      Urogenital Distress Inventory questionnaires. These results do not support a
      simultaneous routine prophylactic colposuspension procedure.

PMID- 23157607
TI  - Non-IBD immunological diseases are a risk factor for reduced survival in PSC.
AB  - BACKGROUND: Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver
      disease. It is known to be associated with immunological diseases (IDs), such as
      inflammatory bowel disease (IBD) and autoimmune hepatitis (AIH). AIM: We
      evaluated the presence of IDs besides IBD and AIH in a cohort of PSC patients,
      and its association with clinical outcome. METHODS: This is a prospective cohort
      study of 195 PSC patients that were evaluated over the period 1987-2010 in our
      tertiary care centre. The presence of ID was determined using a retrospective
      chart review. IDs were subclassified into autoimmune disease (AID) and immune
      mediated inflammatory disease (IMID), according to current guidelines. RESULTS:
      Twenty-seven of 195 (13.8%) PSC patients had at least one additional ID other
      than IBD (70%) or AIH (5%). The most frequent AIDs were autoimmune thyroiditis
      (2.6%) and diabetes mellitus type 1 (2.1%). The most frequent IMIDs were
      psoriasis (3.6%) and sarcoidosis (2.1%). After more than 20 years of follow-up,
      concomitant IDs represent an independent risk factor for reduced transplantation
      free survival in patients with PSC (mean: 8.9 years vs. 16.3 years, P = 0.012).
      Further subgroup analysis revealed a significantly reduced survival especially in
      patients with concomitant IMID (P = 0.017). CONCLUSION: Patients with concomitant
      IDs, especially IMID, are a clinically important subgroup of PSC patients. This
      significant phenotype warrants further genetic and immunological studies.

PMID- 23157608
TI  - Antiplatelet therapy in the prevention of coronary syndromes: mode of action,
      benefits, drawbacks.
AB  - Blood platelets play a key role in normal hemostasis but also in atherothrombosis
      due to their ability of thrombus formation at site of a ruptured atherosclerotic
      plaque. Platelets are also involved in vascular inflammation due to interactions
      with endothelial cells, leukocytes, and smooth muscle cells that may result in an
      excessive fibroproliferative response after vessel dilatation. This review
      article describes both, the current status of standard anti-platelet drug therapy
      using acetylsalicylic acid, adenosine diphosphate or glycoprotein IIb-IIIa
      receptor antagonists in the prevention of cardiovascular events as well as
      drawbacks like non-responsiveness or increased bleeding rates leading to enhanced
      reintervention and transfusion rates, both responsible for adverse clinical
      outcomes after coronary interventions.

PMID- 23157609
TI  - Microwave spectra, planarity, and conformational preferences of cis- and trans-N
      vinylformamide.
AB  - The microwave spectra of a mixture of cis- and trans-H-N-C-O forms of N
      vinylformamide, (H(2)C?CHNHC(?O)H), have been measured at room temperature in the
      18-75 GHz spectral range. The spectra of two forms were assigned. The first of
      these forms has a cis arrangement for the H-N-C-O chain of atoms, whereas the
      second form has a trans arrangement. The C-C-N-C chain of atoms is antiperiplanar
      (180 degrees ) in both forms. The inertial defect of the ground vibrational state
      of cis is -0.142(5) * 10(-20) u m(2), whereas this parameter is -0.087098(26) *
      10(-20) u m(2) for trans. It is concluded that the equilibrium structures of both
      cis and trans are completely planar. The dipole moment determined from Stark
      effect measurements is MU(a) = 9.96(8), MU(b) = 2.22(3), MU(c) = 0 (by symmetry),
      and MU(tot) = 10.20(8) * 10(-30) C m [3.06(2) D], for cis, and MU(a) = 7.64(16),
      MU(b) = 9.24(10), MU(c) = 0 (by symmetry), and MU(tot) = 12.0(2) * 10(-30) C m
      [3.59(5) D] for trans. The spectrum of one vibrationally excited state,
      presumably the first excited state of the torsion about the C-N bond of cis, was
      assigned and the frequency of this state was determined to be 76(15) cm(-1) by
      relative intensity measurements. The spectra of two vibrationally excited states
      of trans were assigned. These states are assumed to be the first excited state of
      the torsion about the C-N bond, and a low bending vibration. Relative intensity
      measurements yielded 101(20) and ca. 300 cm(-1), respectively, for the
      frequencies of these normal vibrations. Accurate values of the quartic
      centrifugal distortion constants, the dipole moments, and the vibration-rotation
      constants have been obtained for both cis and trans. The experimental work has
      been augmented by high-level quantum chemical calculations at the B3LYP/cc-pVTZ
      and CCSD(T)/cc-pVTZ levels of theory. The theoretical calculation performed
      without symmetry restrictions correctly predict that cis and trans are both
      planar. The CCSD(T) rotational constants are in excellent agreement with their
      experimental counterparts, whereas the B3LYP quartic centrifugal distortion
      constants and the vibration-rotation constants are in fairly good agreement with
      experiments. The CCSD(T) dipole moments deviate more than expected from the
      experimental dipole moments. It is estimated that further conformers of cis and
      trans must be at least 4 kJ/mol higher in energy.

PMID- 23157610
TI  - Haemoglobin A2 analysis.

PMID- 23157611
TI  - Whole-body vibration improves functional recovery in spinal cord injured rats.
AB  - Whole-body vibration (WBV) is a relatively novel form of exercise used to improve
      neuromuscular performance in healthy individuals. Its usefulness as a therapy for
      patients with neurological disorders, in particular spinal cord injury (SCI), has
      received little attention in clinical settings and, surprisingly, even less in
      animal SCI models. We performed severe compression SCI at a low-thoracic level in
      Wistar rats followed by daily WBV starting 7 (10 rats) or 14 (10 rats) days after
      injury (WBV7 and WBV14, respectively) and continued over a 12-week post-injury
      period. Rats with SCI but no WBV training (sham, 10 rats) and intact animals (10
      rats) served as controls. Compared to sham-treated rats, WBV did not improve BBB
      score, plantar stepping, or ladder stepping during the 12-week period.
      Accordingly, WBV did not significantly alter plantar H-reflex, lesion volume,
      serotonergic input to the lumbar spinal cord, nor cholinergic or glutamatergic
      inputs to lumbar motoneurons at 12 weeks after SCI. However, compared to sham,
      WBV14, but not WBV7, significantly improved body weight support (rump-height
      index) during overground locomotion and overall recovery between 6-12 weeks and
      also restored the density of synaptic terminals in the lumbar spinal cord at 12
      weeks. Most remarkably, WBV14 led to a significant improvement of bladder
      function at 6-12 weeks after injury. These findings provide the first evidence
      for functional benefits of WBV in an animal SCI model and warrant further
      preclinical investigations to determine mechanisms underpinning this noninvasive,
      inexpensive, and easily delivered potential rehabilitation therapy for SCI.

PMID- 23157613
TI  - Friction and slip at the solid/liquid interface in vibrational systems.
AB  - Molecular dynamics simulations have been performed to study frictional slip and
      its influence on energy dissipation and momentum transfer at atomically smooth
      solid/water interfaces. By modifying the surface chemistry, we investigate the
      relationship between slip and the mechanical response of a vibrating solid for
      both hydrophilic and hydrophobic surfaces. We discover physical phenomena that
      emerge at high frequencies and that have significant contributions to energy
      dissipation. A new analytical model is developed to describe the mechanical
      response of the resonators in this high-frequency regime, which is relevant in
      such applications as microelectromechanical-system-based biosensors. We find a
      linear relationship between the slip length and the ratio of the damping rate
      shift to the resonant frequency shift, which provides a new way to obtain
      information about the slip length from experiments.

PMID- 23157612
TI  - Safety results from a pooled analysis of randomized, controlled phase II and III
      clinical trials and interim data from an open-label extension trial of the
      interleukin-12/23 monoclonal antibody, briakinumab, in moderate to severe
      psoriasis.
AB  - BACKGROUND: Anti-interleukin-12/23 treatment (anti-IL-12/23) has recently
      demonstrated significant efficacy for moderate to severe psoriasis, yet potential
      safety signals warrant further investigation. OBJECTIVES: Expand safety findings
      for the anti-IL-12/23, briakinumab, beyond individual phase II and III clinical
      trials. METHODS: Safety data pooled from five phase II and III clinical trials
      (parent studies) and an open-label extension study (OLE), through 22 October
      2010; patients with >= 1 dose of briakinumab in a parent study or the OLE are
      included. All parent study briakinumab treatment groups were combined with the
      OLE population, which received 100-mg briakinumab every 4 weeks. Adverse events
      (AEs) were collected from the first dose of briakinumab, whether in a parent
      study or the OLE, through 45 days post-last dose. RESULTS: Two thousand five
      hundred and twenty patients (4704 patient-years drug exposure) received >= 1 dose
      of briakinumab during the interim period: 5.6% withdrew due to AEs. Serious
      infections occurred in 1.3% and malignancies in 2.6% (including 1.0% basal cell
      carcinoma, 0.8% squamous cell carcinoma). Twenty-seven major adverse
      cardiovascular events (MACE) occurred, seven in one parent study and 20 in the
      OLE (incidence = 0.57 events/100 PY). Four cardiovascular risk factors were
      retrospectively found to be significant predictors for MACE during briakinumab
      exposure: history of cardiovascular disease, diabetes, body mass index (>= 30)
      and baseline blood pressure (systolic >= 140 or diastolic >= 90). CONCLUSIONS:
      Pooled briakinumab safety results from five parent studies and an OLE suggest
      increased rates of infections, malignancies and MACE, and that patients receiving
      anti-IL-12/23 treatment for moderate to severe psoriasis should be monitored for
      these potential safety signals.

PMID- 23157614
TI  - Investigation of BRAF V600E mutation in papillary thyroid carcinoma and tumor
      surrounding nontumoral tissues.
AB  - The aim of this study was to investigate the association between the BRAF V600E
      mutation incidence and histopathologic prognostic risk factors for papillary
      thyroid carcinoma (PTC) on the Turkish population. The contribution of BRAF V600E
      mutation in both tumor and tumor-surrounding nontumoral tissues of 108 patients
      with PTC was assessed using mutant allele-specific amplification-polymerase chain
      reaction. The BRAF V600E mutation was found in 52.8% of the tumor tissues, and
      7.4% of the tumor-surrounding nontumoral tissues. The BRAF V600E mutation was
      significantly higher in the tumor tissues of the classic variant of PTC (CVPTC)
      cases than the follicular variant of PTC cases (p=0.001). The presence of the
      BRAF V600E mutation was more frequent in women, but this gender difference was
      not statistically significant. BRAF V600E mutation was more frequent in patients
      with either one of adenomatous hyperplasia or diffuse hyperplasia in tumor
      surrounding nontumoral tissues (p=0.012). There was no significant difference in
      the BRAF V600E mutation distribution among tumor-surrounding nontumoral tissues
      of the two PTC variants, but it was more frequent in the CVPTC. Recent data
      suggest that BRAF V600E is an important marker, especially, for CVPTC. We propose
      that patients who had subtotal thyroid resection might have an increased risk of
      recurrence at the residual thyroid tissue if they have BRAF V600E mutation in
      their tumor-surrounding nontumoral tissues.

PMID- 23157616
TI  - Reaching for better understanding across the globe.

PMID- 23157615
TI  - Expression of the platencin biosynthetic gene cluster in heterologous hosts
      yielding new platencin congeners.
AB  - Platensimycin (PTM) and platencin (PTN) are potent and selective inhibitors of
      bacterial and mammalian fatty acid synthases and have emerged as promising drug
      leads for both antibacterial and antidiabetic therapies. We have previously
      cloned and sequenced the PTM-PTN dual biosynthetic gene cluster from Streptomyces
      platensis MA7327 and the PTN biosynthetic gene cluster from S. platensis MA7339,
      the latter of which is composed of 31 genes encoding PTN biosynthesis,
      regulation, and resistance. We have also demonstrated that PTM or PTN production
      can be significantly improved upon inactivation of the pathway-specific regulator
      ptmR1 or ptnR1 in S. platensis MA7327 or MA7339, respectively. We now report
      engineered production of PTN and congeners in a heterologous Streptomyces host.
      Expression constructs containing the ptn biosynthetic gene cluster were
      engineered from SuperCos 1 library clones and introduced into five model
      Streptomyces hosts, and PTN production was achieved in Streptomyces lividans K4
      114. Inactivation of ptnR1 was crucial for expression of the ptn biosynthetic
      gene cluster, thereby PTN production, in S. lividans K4-114. Six PTN congeners,
      five of which were new, were also isolated from the recombinant strain S.
      lividans SB12606, revealing new insights into PTN biosynthesis. Production of PTN
      in a model Streptomyces host provides new opportunities to apply combinatorial
      biosynthetic strategies to the PTN biosynthetic machinery for structural
      diversity.

PMID- 23157617
TI  - Differential interactions of virulent and non-virulent H. parasuis strains with
      naive or swine influenza virus pre-infected dendritic cells.
AB  - Pigs possess a microbiota in the upper respiratory tract that includes
      Haemophilus parasuis. Pigs are also considered the reservoir of influenza viruses
      and infection with this virus commonly results in increased impact of bacterial
      infections, including those by H. parasuis. However, the mechanisms involved in
      host innate responses towards H. parasuis and their implications in a co
      infection with influenza virus are unknown. Therefore, the ability of a non
      virulent H. parasuis serovar 3 (SW114) and a virulent serovar 5 (Nagasaki)
      strains to interact with porcine bone marrow dendritic cells (poBMDC) and their
      modulation in a co-infection with swine influenza virus (SwIV) H3N2 was examined.
      At 1 hour post infection (hpi), SW114 interaction with poBMDC was higher than
      that of Nagasaki, while at 8 hpi both strains showed similar levels of
      interaction. The co-infection with H3N2 SwIV and either SW114 or Nagasaki induced
      higher levels of IL-1beta, TNF-alpha, IL-6, IL-12 and IL-10 compared to mock or
      H3N2 SwIV infection alone. Moreover, IL-12 and IFN-alpha secretion differentially
      increased in cells co-infected with H3N2 SwIV and Nagasaki. These results pave
      the way for understanding the differences in the interaction of non-virulent and
      virulent strains of H. parasuis with the swine immune system and their modulation
      in a viral co-infection.

PMID- 23157618
TI  - The effect of academic exam stress on mucosal and cellular airway immune markers
      among healthy and allergic individuals.
AB  - Research suggests that psychological stress can exacerbate allergies, but
      relatively little is known about the effect of stress on mucosal immune processes
      central to allergic pathophysiology. In this study, we quantified vascular
      endothelial growth factor (VEGF), interferon gamma (IFN-gamma), and interleukin-4
      concentrations in saliva (S) and exhaled breath condensate (EBC) during final
      exams and at midsemester among 23 healthy and 21 allergic rhinitis individuals.
      IFN-gammas decreased during exams for both groups while VEGF(EBC) increased (and
      increases in VEGFs were a trend). Elevated negative affect ratings predicted
      higher VEGF(EBC) in allergic individuals. IFN-gamma(EBC) increased in healthy
      individuals early during exams and then decreased, while allergic individuals
      showed a decrease in IFN-gamma(EBC) throughout final exams. These findings
      suggest that psychological stress can suppress cellular immune function among
      allergic individuals while increasing VEGF.

PMID- 23157619
TI  - Wiskott-Aldrich syndrome caused by a new mutation associated with multifocal
      dermal juvenile xanthogranulomas.
AB  - Wiskott-Aldrich syndrome is a rare X-linked primary immunodeficiency clinically
      characterized by the triad of microthrombocytopenia, immunodeficiency, and
      eczema. Juvenile xanthogranuloma is a well-recognized benign disorder of infancy
      and early childhood from the group of non-Langerhans cell histiocytoses, with a
      good prognosis and spontaneous involution. We report a boy with Wiskott-Aldrich
      syndrome caused by a new, not previously described mutation associated with
      multifocal juvenile xanthogranuloma. 

PMID- 23157620
TI  - Preparation of an immunoaffinity column for the clean-up of fermented food
      samples contaminated with citrinin.
AB  - An immunoaffinity column (IAC) for the clean-up of citrinin-contaminated food
      samples was prepared by using silica gel immobilised with a anti-citrinin
      antibody. Antibodies produced against citrinin-bovine serum albumin (BSA) were
      covalently immobilised onto a silica-based solid support to prepare the IAC. The
      selective extraction and clean-up ability of the IAC was evaluated by capillary
      zone electrophoresis coupled with ultraviolet detection. Clean-up conditions such
      as eluting solutions kind, concentrations, pH and volumes were optimised for
      citrinin by using the IAC. IACs were applied to citrinin-contaminated foods such
      as red yeast rice and monascus colour. The method's performance was acceptable in
      terms of recoveries, which ranged from 80.4% to 97.1% for citrinin-spiked samples
      at levels of 50, 100 and 200 ug kg(-1), and the relative standard deviation
      ranged from 5.3% to 10.5%.

PMID- 23157621
TI  - Thinning segregated graphene layers on high carbon solubility substrates of
      rhodium foils by tuning the quenching process.
AB  - We report the synthesis of large-scale uniform graphene films on high carbon
      solubility substrates of Rh foils for the first time using an ambient-pressure
      chemical vapor deposition method. We find that, by increasing the cooling rate in
      the growth process, the thickness of graphene can be tuned from multilayer to
      monolayer, resulting from the different segregation amount of carbon atoms from
      bulk to surface. The growth feature was characterized with scanning electron
      microscopy, Raman spectra, transmission electron microscopy, and scanning
      tunneling microscopy. We also find that bilayer or few-layer graphene prefers to
      stack deviating from the Bernal stacking geometry, with the formation of
      versatile moire patterns. On the basis of these results, we put forward a
      segregation growth mechanism for graphene growth on Rh foils. Of particular
      importance, we propose that this randomly stacked few-layer graphene can be a
      model system for exploring some fantastic physical properties such as van Hove
      singularities.

PMID- 23157622
TI  - Molecular bases of antipsychotic drugs: the contribution of neurosciences.

PMID- 23157623
TI  - A genetic dissection of antipsychotic induced movement disorders.
AB  - BACKGROUND: Antipsychotic medications (APM) are the first line pharmacological
      treatment for psychotic disorders and other behavioral disorders. Nevertheless,
      their use causes a number of side effects, including extrapyramidal symptoms
      (EPS). EPS decrease the efficacy of the antipsychotic treatments by causing
      poorer compliance to the treatment, stigma and a poorer quality of life for
      patients. Genetic studies hold the potential to unravel the molecular
      underpinnings of the EPS induced by APM but results are not conclusive and are
      far to be used in clinical practice despite decades of research. A more
      sophisticated selection of the list of genetic mutations explaining the genetic
      variance of EPS induced by APM could help in the definition of a personalized
      treatments for patients. Moreover, it would increase the quality of the current
      treatments with APM. METHODS: We reviewed the literature searching for the
      genetic association studies focused on dystonia, parkinsonism, akathisia and
      tardive dyskinesia. Moreover, we reviewed the current biological knowledge of the
      APM induced side effects. Finally, we provide a reasoned list of candidate genes
      and their genetic variations, with the aim of identifying a list of candidates
      for APM induced EPS genetic investigations. RESULTS: Variations located within
      PIK3CA (phosphoinositide-3- kinase, catalytic, alpha polypeptide), PLA2G4A
      (phospholipase A2, group IVA, cytosolic, calcium-dependent), PRKCA (protein
      kinase C, alpha), PRKACG (Phosphatidylinositol-4,5-bisphosphate 3-kinase 110 kDa
      catalytic subunit gamma), ERK-1 (extracellular signalregulated kinase 1 (MAPK3)),
      ERK-2 (extracellular signal-regulated kinase 2 (MAPK1)), GNAS (guanine nucleotide
      binding protein (G protein), alpha stimulating activity polypeptide 1), PLCB1
      (phospholipase C, beta 1 (phosphoinositide-specific)) and ITPR1 (inositol 1,4,5
      triphosphate receptor type 1) were found to be relevant for APM induced EPS. Some
      of the genes are classical candidates for this kind of research, others were
      never investigated. For each of these genes we provide a list of variations that
      balances the limitations of multitesting with the advantages of the tagging
      approach. CONCLUSIONS: We undertook a review of the literature about the APM
      induced EPM to provide some rational genetic candidates to be tested in further
      genetic investigations.

PMID- 23157624
TI  - Neurotransmitters, psychotropic drugs and microglia: clinical implications for
      psychiatry.
AB  - Psychiatric disorders have long and dominantly been regarded to be induced by
      disturbances of neuronal networks including synapses and neurotransmitters. Thus,
      the effects of psychotropic drugs such as antipsychotics and antidepressants have
      been understood to modulate synaptic regulation via receptors and transporters of
      neurotransmitters such as dopamine and serotonin. Recently, microglia,
      immunological/inflammatory cells in the brain, have been indicated to have
      positive links to psychiatric disorders. Positron emission tomography (PET)
      imaging and postmortem studies have revealed microglial activation in the brain
      of neuropsychiatric disorders such as schizophrenia, depression and autism.
      Animal models of neuropsychiatric disorders have revealed the underlying
      microglial pathologies. In addition, various psychotropic drugs have been
      suggested to have direct effects on microglia. Until now, the relationship
      between microglia, neurotransmitters and psychiatric disorders has not been well
      understood. Therefore, in this review, at first, we summarize recent findings of
      interaction between microglia and neurotransmitters such as dopamine, serotonin,
      norepinephrine, acetylcholine and glutamate. Next, we introduce up-to-date
      knowledge of the effects of psychotropic drugs such as antipsychotics,
      antidepressants and antiepileptics on microglial modulation. Finally, we propose
      the possibility that modulating microglia may be a key target in the treatment of
      various psychiatric disorders. Further investigations and clinical trials should
      be conducted to clarify this perspective, using animal in vivo studies and
      imaging studies with human subjects.

PMID- 23157625
TI  - Effects of antipsychotics on the BDNF in schizophrenia.
AB  - Brain-derived neurotropic factor (BDNF) is involved in the development of the
      brain, and likely influences the neuroplasticity in schizophrenia. BDNF is also
      believed to interact with other neurotransmitter systems implicated in
      schizophrenia, such as dopamine, glutamate, serotonin and GABA. Therefore, BDNF
      is a candidate gene for schizophrenia. In past decades, the blood (serum or
      plasma) BDNF protein levels and BDNF gene alleles and genotypes to the clinical
      features of schizophrenia, such as age of onset, clinical subtypes, symptom
      severity, and drug response, have been evaluated among different populations.
      However, the results are still inconsistent. Further, different drugs have been
      reported to have different effects on BDNF protein levels. A cross-sectional
      survey revealed that serum BDNF levels in chronic schizophrenic patients treated
      with clozapine exceeded those of patients treated with risperidone or with
      typical antipsychotics. In recent times, BDNF epigenetic studies have also been
      conducted in clinical studies of schizophrenia to address the question of why
      patients with the same gene genotype and alleles have different clinical
      presentations. In addition, the effects of different antipsychotic drugs on gene
      methylation and protein acetylation have also been reported. In conclusion, more
      data are needed regarding BDNF in the brain and in peripheral blood, including
      protein levels, single nucleotide polymorphisms, epigenetic regulation, and
      clinical data in order to understand the role of BDNF in schizophrenia.

PMID- 23157626
TI  - Recent developments in neurochemical imaging in schizophrenia: an update.
AB  - The advent of neurochemical brain imaging methods has provided an opportunity to
      study the neurochemistry of the human brain in normal and abnormal development.
      The aim of this article is to provide an update on recent major developments in
      neurochemical imaging in schizophrenia research. In this concise review, we
      discuss the major findings on three neurotransmitters, namely dopamine, serotonin
      and glutamate. The most promising radioligand for D(2)/D(3) neuroreceptor imaging
      is the agonist [(11)C]PHNO, with higher in vivo affinity for D(3) than D(2)
      receptors, which can be used to measure amphetamine-induced release of dopamine,
      and therefore a potential model of dopaminergic alterations in schizophrenia.
      Recent development of selective radiotracers allow imaging of the serotonin
      transporter (SERT) using positron emission tomography (PET) with selective
      tracers such as [(11)C]DASB. Additionally, the glutamatergic hypothesis has
      evolved from theory to phase III clinical trials of newer agents with novel
      mechanisms. With the development of newer radioligands and the in vivo
      application of magnetic resonance spectroscopy (MRS) at relatively high magnetic
      field strengths, there is ample scope for further neuroimaging advances.

PMID- 23157627
TI  - Facilitative effect of serotonin(1A) receptor agonists on cognition in patients
      with schizophrenia.
AB  - Disturbances of cognitive function are considered to largely affect the outcome
      in patients with schizophrenia. There is much attention to the role of
      psychotropic compounds acting on serotonin (5-HT) receptors in ameliorating
      cognitive deficits of the disease. Among the 5-HT receptor subtypes, the 5-HT(1A)
      receptor is attracting particular interests as a potential target for enhancing
      cognition, based on preclinical and clinical evidence. The neural network
      underlying the ability of 5-HT(1A) agonists to treat cognitive impairments of
      schizophrenia likely includes dopamine, glutamate, and gamma-aminobutyric acid
      neurons. Recent advances of electrophysiological measures, such as event-related
      potentials, have provided insights into facilitative effects on cognition of some
      atypical antipsychotic drugs or related compounds acting directly or indirectly
      on 5-HT(1A) receptors. These considerations are expected to promote the
      development of novel therapeutics for the betterment of functional outcome in
      people suffering from schizophrenia.

PMID- 23157628
TI  - The role of GABA-A receptor in the synergism between SSRI and antipsychotic in
      schizophrenia; implications for antipsychotic modes of actions.
AB  - Antipsychotics, old and new varieties, are effective against positive symptoms
      such as hallucination and delusions, but are often of limited value in treating
      core features of schizophrenia particularly negative symptoms. Developments of
      new drugs based on current dogmas have produced similar drugs with no
      breakthroughs in effectiveness. New knowledge as to which mechanisms are
      responsible for symptom productions and treatment is needed. There is evidence
      that response may improve when antipsychotics are augmented with selective
      serotonin reuptake inhibitor (SSRI). This augmenting effect cannot be explained
      by summating pharmacological effects of the individual drugs. In a series of
      laboratory and clinical studies, we identified unique biochemical effects of the
      SSRI-Antipsychotic combination, different from each individual drug and suggested
      that some of these may mediate the clinical effect. In this paper, we review
      these studies and propose that modulation of the gamma-aminobutyric acid (GABA)-A
      receptor and its regulating system is the mechanism by which SSRI antipsychotic
      synergism exerts its clinical efficacy.

PMID- 23157629
TI  - Serotonin receptors of type 6 (5-HT6): from neuroscience to clinical
      pharmacology.
AB  - The serotonin (5-HT) receptors of type 6 (5-HT6) are quite different from all
      other 5-HT receptors, as they include a short third cytoplasmatic loop and a long
      C-terminal tail, and one intron located in the middle of the third cytoplasmatic
      loop. A lot of controversies still exist regarding their binding affinity,
      effects of 5-HT6 ligands on brain catecholamines, behavioral syndromes regulated
      by them, and brain distribution. In spite of the lack of information on metabolic
      pattern of the various compounds, some of 5-HT6 receptor ligands entered the
      clinical development as potential anti-dementia, antipsychotic, antidepressant
      and anti-obese drugs. The present paper is a comprehensive review on the state of
      art of the 5-HT6 receptors, while highlighting the potential clinical
      applications of 5-HT6 receptor agonists/antagonists.

PMID- 23157630
TI  - Molecular imaging PET and SPECT approaches for improving productivity of
      antipsychotic drug discovery and development.
AB  - The need for innovation in research is leading to an increased use of imaging
      biomarkers, which have shown to reduce timings and increase productivity, thus
      saving costs. PET and SPECT neurotransmission imaging has shown usefulness in the
      discovery and development of drugs for the central nervous system, providing
      unique information on drug-target interactions in the living human brain. Among
      the different therapeutic areas, antipsychotic drugs pioneered the application of
      these technologies in early phases of development. PET and SPECT radioligands for
      the most commonly targeted neurotransmission systems in the development of these
      drugs, such as the dopaminergic and serotoninergic systems are available, thus
      fostering the inclusion of PET and SPECT studies in the antipsychotic drug
      development plans. Radioligands for other neurotransmission systems more recently
      implicated in the pathophysiology of schizophrenia, such as the glutamatergic
      system, are being currently investigated. This review focuses on
      neurotransmission PET and SPECT aiming to serve as guidance for procedure
      requirements and methodology choices to be applied in antipsychotic drug
      development, through specific examples. Cutting-edge study designs and
      quantification approaches will be reviewed. Finally, some clues to get the most
      out of the PET and SPECT studies in the development of antipsychotic drugs will
      be provided.

PMID- 23157631
TI  - Neurobiological basis of dyskinetic effects induced by antipsychotics: the
      contribution of animal models.
AB  - Tardive dyskinesia (TD) is a movement disorder characterized by abnormal
      involuntary facial movements induced by chronic therapy with classical
      antipsychotic medications. Currently, there is no satisfactory pharmacotherapy
      for TD, which represents a major limitation to therapy with classical
      antipsychotics. In order to develop or optimize therapies for TD, and to develop
      new APDs with lower indices of motor side effects, the pathology underlying TD
      must first be understood. The use of animal models has been used to further this
      objective. Here, we review different preparations that have been used to model TD
      and discuss the contribution of neuroimaging studies conducted in these models.
      Studies in animal models have lead to several hypotheses of TD pathology,
      although none has yet emerged as the ultimate underlying cause of this syndrome.
      We discuss alterations in functional indices, neuron and synapse morphology and
      changes in specific neurotransmitter systems that have been described in animal
      models of TD, and outline how these findings have contributed to our
      understanding of antipsychotic-induced dyskinesias. We conclude that several non
      mutually exclusive theories of TD are supported by animal studies, including
      increases in oxidative stress leading to structural and functional changes in
      specific neurotransmitter systems. Elucidating the mechanisms underlying TD
      neuropathology partly through the use of animal models will lead to the
      development of APDs with superior side effect profiles or more effective
      therapies for TD.

PMID- 23157633
TI  - Transcranial brain stimulation in schizophrenia: targeting cortical excitability,
      connectivity and plasticity.
AB  - Transcranial magnetic stimulation (TMS) is a very popular tool used within
      neuroscience. This and other associated techniques allow the in vivo
      investigation of cortical excitability, cortical connectivity and cortical
      plasticity. Schizophrenia is a brain disorder and various theories other than the
      dopamine hypothesis have been developed to describe its underlying neurobiology.
      Supported by animal and post mortem studies, findings from TMS studies indicate
      that schizophrenia is a disease of reduced cortical inhibition and impaired intra
      and intercortical connectivity. Further studies using repetitive TMS and other
      plasticity-inducing techniques have shown that cortical plasticity is altered in
      schizophrenia patients, supporting the recently discussed plasticity deficiency
      theory of schizophrenia. This review gives an introduction to the most frequently
      applied techniques, describes findings in schizophrenia patients and discusses
      these findings with regard to the neurotransmitters and associated receptors
      involved. In summary, there is emerging evidence of an important
      pathophysiological interplay between reduced inhibition, impaired connectivity
      and reduced plasticity in schizophrenia patients. Gamma-aminobutyric-acid
      receptors and glutamtergic N-Methyl-D-aspartic-acid-receptors are most likely to
      be involved in this complex interplay, which may reflect a disturbed signal-to
      noise ratio in schizophrenia patients. This review will discuss this issue with
      regard to the available treatment options and will give implications for future
      research and therapeutic strategies regarding disinhibition and neuroplasticity
      in schizophrenia.

PMID- 23157632
TI  - Abnormal striatal dopamine transmission in schizophrenia.
AB  - Despite numerous revisions and reformulations, dopamine (DA) hypothesis of
      schizophrenia remains a pivotal neurochemical hypothesis of this illness. The aim
      of this review is to expose and discuss findings from positron emission
      tomography (PET) or single-photon- emission computed tomography (SPECT) studies
      investigating DA function in the striatum of medicated, drug-naive or drug-free
      patients with schizophrenia and in individuals at risk compared with healthy
      volunteers. DA function was studied at several levels: i) at a presynaptic level
      where neuroimaging studies investigating DOPA uptake capacity clearly show an
      increase of DA synthesis in patients with schizophrenia; ii) at a synaptic level
      where neuroimaging studies investigating dopamine transporter availability (DAT)
      does not bring any evidence of dysfunction; iii) and finally, neuroimaging
      studies investigating DA receptor density show a mild increase of D2 receptor
      density in basic condition and, an hyperreactivity of DA system in dynamic
      condition. These results are discussed regarding laterality, sub-regions of
      striatum and implications for the at-risk population. Striatal DA abnormalities
      are now clearly demonstrated in patients with schizophrenia and at risk
      population and could constitute an endophenotype of schizophrenia. Subtle sub
      clinical striatal DA abnormalities in at risk population could be a biomarker of
      transition from a vulnerability state to the expression of frank psychosis.

PMID- 23157634
TI  - Proton magnetic resonance spectroscopy changes after antipsychotic treatment.
AB  - Proton magnetic resonance spectroscopy ((1)H MRS) enables the observation of
      brain function in vivo. Several brain metabolites can be measured by the means of
      (1)H MRS: N-acetylaspartate (NAA), choline containing compounds (Cho), myo
      inositol (mI) and glutamate (Glu), glutamine (Gln) and GABA (together as Glx
      complex or separately). (1)H MRS measures have been found to be abnormal in
      psychotic disorders such as schizophrenia. Here we specifically review the
      influence exerted by antipsychotic drugs on brain metabolism, as detected by (1)H
      MRS. We systematically reviewed the available literature and uncovered 27
      studies, 16 before-after treatment and 11 cross-sectional. Most of them addressed
      the effects of antipsychotics in schizophrenia and mainly focusing on NAA
      alterations. Follow up studies indicated antipsychotic drugs may act by
      increasing NAA levels in selected brain areas (the frontal lobe and thalamus),
      especially during the short-time observation. This phenomenon seems to vanish
      after longer observation. Other studies indicated that glutamate measures are
      decreasing along with the duration of the disease, suggesting both a
      neurodegenerative process present in schizophrenic brain as well as an influence
      of antipsychotics. The above results were reviewed according to the most recent
      theories in the field accounting for the impact of antipsychotics (1)HMRS
      measures.

PMID- 23157637
TI  - Systematic review of the influence of antipsychotics on the blood oxygenation
      level-dependent signal of functional magnetic resonance imaging.
AB  - Functional Magnetic Resonance Imaging (FMRI) is a non-invasive technique for
      brain mapping and mostly performed using changes of the blood-oxygen-level
      dependent (BOLD)-signal. It has been widely used to investigate patients with
      schizophrenia. Most of the studies examine patients treated with antipsychotic
      drugs, although little is known about the effects of these drugs on the
      BOLDsignal. Here we examined studies of patients with schizophrenia treated with
      different antipsychotics to address the question whether and to what extent
      antipsychotic drugs in themselves produce BOLD-signal changes. We performed a
      PubMed-search for the period from 1999 until January 2012 with the search items
      "schizophrenia" and "Magnetic Resonance Imaging" and "Antipsychotic Agents; or
      "Magnetic Resonance Imaging" and "Antipsychotic Agents"; or "schizophrenia" and
      "Antipsychotic Agents" and "FMRI". We extracted articles that examined at least
      two patient groups with different treatments, or patients examined on different
      medications at different times and that provided information about drug effects.
      No common effect of antipsychotics on BOLD-signal was found. However, based on
      the results for different antipsychotics (haloperidol, olanzapine, quetiapine and
      risperidone) we found evidence that the affinity to the dopamine (DA) D(2)
      receptor may influence BOLD-signal.

PMID- 23157636
TI  - Volumetric changes in the basal ganglia after antipsychotic monotherapy: a
      systematic review.
AB  - INTRODUCTION: Exposure to antipsychotic medication has been extensively
      associated with structural brain changes in the basal ganglia (BG). Traditionally
      antipsychotics have been divided into first and second generation antipsychotics
      (FGAs and SGAs) however, the validity of this classification has become
      increasingly controversial. To address if specific antipsychotics induce
      differential effects on BG volumes or whether volumetric effects are explained by
      FGA or SGA classification, we reviewed longitudinal structural magnetic resonance
      imaging (MRI) studies investigating effects of antipsychotic monotherapy.
      MATERIAL AND METHODS: We systematically searched PubMed for longitudinal MRI
      studies of patients with schizophrenia or non-affective psychosis who had
      undergone a period of antipsychotic monotherapy. We used specific, predefined
      search terms and extracted studies were hand searched for additional studies.
      RESULTS: We identified 13 studies published in the period from 1996 to 2011.
      Overall six compounds (two classified as FGAs and four as SGAs) have been
      investigated: haloperidol, zuclophentixol, risperidone, olanzapine, clozapine,
      and quetiapine. The follow-up period ranged from 3-24 months. Unexpectedly, no
      studies found that specific FGAs induce significant BG volume increases.
      Conversely, both volumetric increases and decreases in the BG have been
      associated with SGA monotherapy. DISCUSSION: Induction of striatal volume
      increases is not a specific feature of FGAs. Except for clozapine treatment in
      chronic patients, volume reductions are not restricted to specific SGAs. The
      current review adds brain structural support to the notion that antipsychotics
      should no longer be classified as either FGAs or SGAs. Future clinical MRI
      studies should strive to elucidate effects of specific antipsychotic drugs.

PMID- 23157635
TI  - Antipsychotic drug effects in schizophrenia: a review of longitudinal FMRI
      investigations and neural interpretations.
AB  - The evidence that antipsychotics improve brain function and reduce symptoms in
      schizophrenia is unmistakable, but how antipsychotics change brain function is
      poorly understood, especially within neuronal systems. In this review, we
      investigated the hypothesized normalization of the functional magnetic resonance
      imaging (fMRI) blood oxygen level dependent signal in the context of
      antipsychotic treatment. First, we conducted a systematic PubMed search to
      identify eight fMRI investigations that met the following inclusion criteria:
      case-control, longitudinal design; pre- and post-treatment contrasts with a
      healthy comparison group; and antipsychotic-free or antipsychotic-naive patients
      with schizophrenia at the start of the investigation. We hypothesized that
      aberrant activation patterns or connectivity between patients with schizophrenia
      and healthy comparisons at the first imaging assessment would no longer be
      apparent or "normalize" at the second imaging assessment. The included studies
      differed by analysis method and fMRI task but demonstrated normalization of fMRI
      activation or connectivity during the treatment interval. Second, we reviewed
      putative mechanisms from animal studies that support normalization of the BOLD
      signal in schizophrenia. We provided several neuronal-based interpretations of
      these changes of the BOLD signal that may be attributable to long-term
      antipsychotic administration.

PMID- 23157638
TI  - A general approach for combining voxel-based meta-analyses conducted in different
      neuroimaging modalities.
AB  - Meta-analyses are useful to summarize the exponential amount of inconsistent and
      conflicting neuroimaging data. However, they are usually separately conducted for
      each different neuroimaging modality, preventing the multimodal integration of
      different imaging findings in a given neuropsychiatric disorder. Here, we
      describe an innovative method to meta-analytically combine the results of
      different imaging modalities, such as structural and functional paradigms. The
      method accounts for the presence of noise in the estimation of the p-values, and
      can be easily applied to any meta-analytical software. We hope that with this
      advanced imaging tool, researchers will be able to provide more complete
      multimodal pictures of the brain regions affected in different neuropsychiatric
      disorders.

PMID- 23157640
TI  - Prostate cancer, miRNAs, metallothioneins and resistance to cytostatic drugs.
AB  - MicroRNAs (miRNAs) translationally repressing their target messenger RNAs due to
      their gene-regulatory functions play an important but not unexpected role in a
      tumour development. More surprising are the findings that levels of various
      miRNAs are well correlated with presence of specific tumours and formation of
      metastases. Moreover, these small regulatory molecules play a role in the
      resistance of cancer cells to commonly used anti-cancer drugs, such as cisplatin,
      anthracyclines, and taxanes. In that respect, miRNAs become very attractive
      target for potential therapeutic interventions. Improvements in the sensitivity
      of miRNAs detection techniques led to discovery of circulating miRNAs which
      became very attractive non-invasive biomarker of cancer with a substantial
      predictive value. In this review, the authors focus on i) oncogenic and anti
      tumour acting miRNAs, ii) function of miRNAs in tumour progression, iii) possible
      role of miRNAs in resistance to anticancer drugs, and iv) diagnostic potential of
      miRNAs for identification of cancer from circulating miRNAs with special emphasis
      on prostate cancer. Moreover, relationship between miRNAs and expression of
      metallothionein is discussed as a possible explanation of resistance against
      platinum based drugs.

PMID- 23157639
TI  - Do subjects at clinical high risk for psychosis differ from those with a genetic
      high risk?--A systematic review of structural and functional brain abnormalities.
AB  - INTRODUCTION: Pre-psychotic and early psychotic characteristics are investigated
      in the high-risk (HR) populations for psychosis. There are two different
      approaches based either on hereditary factors (genetic high risk, G-HR) or on the
      clinically manifested symptoms (clinical high risk, C-HR). Common features are an
      increased risk for development of psychosis and similar cognitive as well as
      structural and functional brain abnormalities. METHODS: We reviewed the existing
      literature on longitudinal structural, and on functional imaging studies, which
      included G-HR and/or C-HR individuals for psychosis, healthy controls (HC) and/or
      first episode of psychosis (FEP) or schizophrenia patients (SCZ). RESULTS: With
      respect to structural brain abnormalities, vulnerability to psychosis was
      associated with deficits in frontal, temporal, and cingulate regions in HR, with
      additional insular and caudate deficits in C-HR population. Furthermore, C-HR had
      progressive prefrontal deficits related to the transition to psychosis. With
      respect to functional brain abnormalities, vulnerability to psychosis was
      associated with prefrontal, cingulate and middle temporal abnormalities in HR,
      with additional parietal, superior temporal, and insular abnormalities in C-HR
      population. Transition-to-psychosis related differences emphasized prefrontal,
      hippocampal and striatal components, more often detectable in C-HR population.
      Multimodal studies directly associated psychotic symptoms displayed in altered
      prefrontal and hippocampal activations with striatal dopamine and thalamic
      glutamate functions. CONCLUSION: There is an evidence for similar structural and
      functional brain abnormalities within the whole HR population, with more
      pronounced deficits in the C-HR population. The most consistent evidence for
      abnormality in the prefrontal cortex reported in structural, functional and
      multimodal studies of HR population may underlie the complexity of higher
      cognitive functions that are impaired during HR mental state for psychosis.

PMID- 23157641
TI  - Synthesis and biological evaluation of low molecular weight fluorescent imaging
      agents for the prostate-specific membrane antigen.
AB  - Targeted near-infrared (NIR) optical imaging can be used in vivo to detect
      specific tissues, including malignant cells. A series of NIR fluorescent ligands
      targeting the prostate-specific membrane antigen (PSMA) was synthesized and each
      compound was tested for its ability to image PSMA+ tissues in experimental models
      of prostate cancer. The agents were prepared by conjugating commercially
      available active esters of NIR dyes, including IRDye800CW, IRDye800RS, Cy5.5,
      Cy7, or a derivative of indocyanine green (ICG) to the terminal amine group of
      (S)-2-(3-((S)-5-amino-1-carboxypentyl)ureido)pentanedioic acid 1, (14S,18S)-1
      amino-8,16-dioxo-3,6-dioxa-9,15,17-triazaicosane-14,18,20-tricarboxylic acid 2
      and (3S,7S)-26-amino-5,13,20-trioxo-4,6,12,21-tetraazahexacosane-1,3,7,22
      tetracarboxylic acid 3. The K(i) values for the dye-inhibitor conjugates ranged
      from 1 to 700 pM. All compounds proved capable of imaging PSMA+ tumors
      selectively to varying degrees depending on the choice of fluorophore and linker.
      The highest tumor uptake was observed with IRDye800CW employing a poly(ethylene
      glycol) or lysine-suberate linker, as in 800CW-2 and 800CW-3, while the highest
      tumor to nontarget tissue ratios were obtained for Cy7 with these same linkers,
      as in Cy7-2 and Cy7-3. Compounds 2 and 3 provide useful scaffolds for targeting
      of PSMA+ tissues in vivo and should be useful for preparing NIR dye conjugates
      designed specifically for clinical intraoperative optical imaging devices.

PMID- 23157642
TI  - Positive climate feedbacks of soil microbial communities in a semi-arid
      grassland.
AB  - Soil microbial communities may be able to rapidly respond to changing
      environments in ways that change community structure and functioning, which could
      affect climate-carbon feedbacks. However, detecting microbial feedbacks to
      elevated CO(2)  (eCO(2) ) or warming is hampered by concurrent changes in
      substrate availability and plant responses. Whether microbial communities can
      persistently feed back to climate change is still unknown. We overcame this
      problem by collecting microbial inocula at subfreezing conditions under eCO(2) 
      and warming treatments in a semi-arid grassland field experiment. The inoculant
      was incubated in a sterilised soil medium at constant conditions for 30 days.
      Microbes from eCO(2)  exhibited an increased ability to decompose soil organic
      matter (SOM) compared with those from ambient CO(2)  plots, and microbes from
      warmed plots exhibited increased thermal sensitivity for respiration. Microbes
      from the combined eCO(2)  and warming plots had consistently enhanced microbial
      decomposition activity and thermal sensitivity. These persistent positive
      feedbacks of soil microbial communities to eCO(2)  and warming may therefore
      stimulate soil C loss.

PMID- 23157643
TI  - Do automatic mental associations detect a flashbulb memory?
AB  - Flashbulb memories (FBMs) are defined as detailed memories for the reception
      context in which people first heard of a public and emotionally relevant event.
      For many years researchers have been debating whether FBMs can be considered a
      special class of emotional memories, or whether they suffer the same fate as
      ordinary autobiographical formations. The debate on the real existence of this
      special class of memories reflects the difficulty of establishing their accuracy.
      Three indices have been defined as proxies for FBM accuracy: specificity of
      recalled details, individuals' confidence in their memory, and memory consistency
      over time. However, all approaches to FBM assessment have been based on explicit
      self-report measures. In two studies we aimed to detect FBMs for two emotional
      public events, by simultaneously employing explicit traditional FBM measures and
      implicit measures based on the autobiographical Implicit Association Test (aIAT).
      Jointly considered, the results from the two studies showed that the implicit
      measures were able to discriminate a FBM, and appeared significantly associated
      with explicit traditional measures of FBM Specificity, Confidence, and
      Consistency. Both explicit and implicit assessments concurred to correctly
      estimate a FBM. Implications for the FBM debate are discussed.

PMID- 23157644
TI  - Benefits of an inclusive US education system.
AB  - Presented is a historical perspective of one scientist's journey from war-torn
      Europe to the opportunities presented by a flexible US educational system. It
      celebrates the opening of the science establishment that began in the 1950s and
      its fostering of basic research, and recognizes individuals who were instrumental
      in guiding the author's education as well as those with whom she later
      participated in collaborative algal plant research. The initial discovery and
      later elucidation of phycobilisome structure are elaborated, including the
      structural connection with photosystem II. Furthermore, she summarizes some of
      her laboratory's results on carotenoids and its exploration of the isoprenoid
      pathway in cyanobacteria. Finally, she comments on the gender gap and how her
      generation benefited when opportunities for women scientists were enlarged.

PMID- 23157646
TI  - Living with coeliac disease and a gluten-free diet: a Canadian perspective.
AB  - OBJECTIVE: Strict adherence to a gluten-free diet is the only treatment for
      coeliac disease. The gluten-free diet is complex, costly and impacts on all
      activities involving food, making it difficult to maintain for a lifetime. The
      purpose of this cross-sectional study was to evaluate the difficulties
      experienced, the strategies used and the emotional impact of following a gluten
      free diet among Canadians with coeliac disease. METHODS: A questionnaire was
      mailed to all members (n = 10 693) of both the Canadian Celiac Association and
      the Fondation quebecoise de la maladie coeliaque in 2008. RESULTS: The overall
      response rate was 72%. Results are presented for the 5912 respondents (>=18
      years) reporting biopsy-confirmed coeliac disease and/or dermatitis
      herpetiformis. Two-thirds never intentionally consumed gluten. Women reported
      significantly greater emotional responses to a gluten-free diet but, with time,
      were more accepting of it than men. Difficulties and negative emotions were
      experienced less frequently by those on the diet for >5 years, although food
      labelling and eating away from home remained very problematic. Frustration and
      isolation because of the diet were the most common negative emotions experienced.
      CONCLUSIONS: The present study quantifies the difficulties experienced, the
      strategies used and the emotional impact of following a gluten-free diet. It
      highlights the need to improve the training and education of dietitians, other
      health providers and the food service industry workers about coeliac disease and
      a gluten-free diet, with the aim of better helping individuals improve their
      adherence to a gluten-free diet and their quality of life.

PMID- 23157645
TI  - Toxin-antitoxin loci vapBC-1 and vapXD contribute to survival and virulence in
      nontypeable Haemophilus influenzae.
AB  - BACKGROUND: Nontypeable Haemophilus influenzae (NTHi) is a significant human
      pathogen responsible for respiratory tract infections and the most common cause
      of recurrent otitis media. Type II toxin-antitoxin (TA) systems are genetic
      elements that code for a stable protein toxin and a labile antitoxin that are
      thought to be involved in metabolic regulation of bacteria by enabling a switch
      to a dormant state under stress conditions. The contribution to infection
      persistence of the NTHi TA loci vapBC-1 and vapXD was examined in this study.
      RESULTS: Deletions in vapBC-1, vapXD and vapBC-1 vapXD significantly decreased
      the survival of NTHi co-cultured with primary human respiratory tissue at the air
      liquid interface and in the chinchilla model of otitis media. The TA deletions
      did not affect the growth dynamics of the mutants in rich media, their ultra
      structural morphology, or display appreciable synergy during NTHi infections. The
      toxin and antitoxin proteins of both pairs heterodimerized in vivo. Consistent
      with our previous findings regarding the VapC-1 toxin, the NTHi VapD toxin also
      displayed ribonuclease activity. CONCLUSIONS: We conclude that the vapBC-1 and
      vapXD TA loci enhance NTHi survival and virulence during infection in vitro and
      in vivo using a mechanism of mRNA cleavage, and that these conserved TA pairs
      represent new targets for the prophylaxis and therapy of otitis media and other
      NTHi-caused mucosal diseases.

PMID- 23157647
TI  - Teaching play skills to young children with autism.
AB  - BACKGROUND: Play is critical for the development of young children and is an
      important part of their daily routine. However, children with autism often
      exhibit deficits in play skills and engage in stereotypic behaviour. We reviewed
      studies to identify effective instructional strategies for teaching play skills
      to young children with autism. METHOD: Empirical studies on teaching play skills
      to young children with autism published from 1990 to 2011 were located. These
      studies included single subject and group designs. RESULTS: Twenty-six studies
      were reviewed. The majority of studies on teaching play skills used combined
      interventions. Children with autism improved their play skills, with direct
      intervention embedding their interests during play. Improvements in play skills
      increased positive social interactions and decreased inappropriate behaviour as
      collateral effects. CONCLUSIONS: Further research is needed to develop more
      effective play skill interventions that assess the functional use of play and are
      implemented in the natural environment.

PMID- 23157648
TI  - Radiofrequency ablation of hepatocellular carcinoma: The feasibility of magnetic
      resonance imaging with gadolinium ethoxybenzyl diethylene triamine pentaacetic
      acid for evaluating the ablative margin.
AB  - AIM:   The aim of this study was to evaluate the feasibility of gadolinium
      ethoxybenzyl diethylene triamine pentaacetic acid (Gd-EOB-DTPA) in magnetic
      resonance imaging (MRI) to assess the ablative margin of radiofrequency (RF)
      ablation to hepatocellular carcinoma (HCC). METHODS:   RF ablation was performed
      in the livers of six pigs after the i.v. administration of Gd-EOB-DTPA 20 min
      before ablation. Three pigs were killed 2 h after administration (group A), and
      the other pigs were killed 7 days after ablation (group B). Thereafter,
      correlation between pathological findings and MRI was investigated. Moreover, the
      Gd concentrations were examined in ablated and non-ablated regions. An initial
      clinical evaluation was conducted for 28 HCC nodules. Percutaneous RF ablation
      was performed 20 min after administration, and T(1)-weighted images were taken 2,
      24 and 72 h post-treatment. RESULTS:   On T(1)-weighted images of the porcine
      liver, the RF ablated lesions showed hyperintense regions with hypointense rims,
      which histopathologically corresponded to sinusoidal congestion. The Gd
      concentrations in ablated regions in group A were significantly higher than those
      in non-ablated regions, while the concentrations in both regions in group B fell
      to nearly undetectable levels. In 27 of the 28 HCC nodules, the treated area
      consisted of a hypointense region, indicative of the tumor, and a surrounding
      hyperintense rim 2 h after ablation. Subsequently, a thin hypointense region was
      observed in the outermost layer 24 and 72 h after ablation. CONCLUSION:  
      Administration of Gd-EOB-DTPA in conjunction with RF ablation of HCC may be
      feasible for the assessment of an accurate ablative margin.

PMID- 23157649
TI  - Competition of bovine serum albumin adsorption and bacterial adhesion onto
      surface-grafted ODT: in situ study by vibrational SFG and fluorescence confocal
      microscopy.
AB  - The interaction of hydrophilic and hydrophobic ovococcoid bacteria and bovine
      serum albumin (BSA) proteins with a well ordered surface of octadecanethiol (ODT)
      self assembled monolayer (SAM) has been studied in different situations where
      proteins were either preadsorbed on ODT or adsorbed simultaneously with bacterial
      adhesion as in life conditions. The two situations lead to very different
      antimicrobial behavior. Bacterial adhesion on preadsorbed BSA is very limited,
      while the simultaneous exposure of ODT SAM to proteins and bacteria lead to a
      markedly weaker antimicrobial effect. The combination of sum frequency generation
      spectroscopy and fluorescence confocal microscopy experiments allow one to draw
      conclusions on the factors that govern the ODT SAM or BSA film interaction with
      bacteria at the molecular level. On the hydrophobic ODT surface, interaction with
      hydrophobic or hydrophilic biomolecules results in opposite effects on the SAM,
      namely, a flattening or a raise of the terminal methyl groups of ODT. On an
      amphiphilic BSA layer, the bacterial adhesion strength is weakened by the
      negative charges carried by both BSA and bacteria. Surprisingly, preadsorbed BSA
      that cover part of the bacteria cell walls increase the adhesion strength to the
      BSA film and reduce hydrophobic interactions with the ODT SAM. Finally, bacterial
      adhesion on a BSA film is shown to modify the BSA proteins in some way that
      change their interaction with the ODT SAM. The antimicrobial effect is much
      stronger in the case of a preadsorbed BSA layer than when BSA and bacteria are in
      competition to colonize the ODT SAM surface.

PMID- 23157650
TI  - Theoretical study of the absorption spectrum of a photoisomerizable iron complex.
AB  - We report the time-dependent density functional theory study of the absorption
      spectrum of an iron complex exhibiting photoisomerization properties. The role of
      the exchange-correlation functionals and, in particular, the effects of the
      inclusion of long-range corrections have been considered. The vertical
      transitions have been analyzed in terms of natural transition orbitals and have
      shown that the spectrum is dominated by ligand-to-metal charge-transfer
      transitions, an occurrence that could be promising for future applications of
      these complexes.

PMID- 23157651
TI  - Computer-aided design evaluation of harvestable mandibular bone volume: a
      clinical and tomographic human study.
AB  - PURPOSE: To evaluate and compare the volume of bone graft material that can be
      safely harvested from the mandibular symphysis and rami using a computer-aided
      design (CAD) software program. MATERIALS AND METHODS: Preoperative computerized
      tomography scans from 40 patients undergoing bone augmentation procedures were
      analyzed. Symphysis and rami cross sections were mapped using a CAD software
      program (AutoCAD((r)), Autodesk, Inc., San Rafael, CA, USA) to evaluate the bone
      volume that can be safely harvested. CAD calculations were contrasted to
      intrasurgical measurements in a subgroup of 20 individuals. RESULTS: CAD
      calculations yielded a safe harvestable osseous volume of 1.44 cm(3) +/- 0.49 for
      the symphysis and 0.82 cm(3) +/- 0.21 for each ramus (p < .0001, confidence
      interval [CI] 95%: 0.47-0.78). These measurements were significantly lower (p <
      .0001) than the bone volumes harvested intrasurgically for both symphysis and
      ramus, respectively (2.40 cm(3) +/- 0.50 vs. 2.65 cm(3) +/- 0.45). CAD
      calculations of harvestable symphysis and ramus bone translated into an average
      of 2.40 cm(3) +/- 0.50 (range: 1.80-3.10 cm(3)) and 2.65 cm(3) +/- 0.45 (range:
      1.90-3.50) of particulate bone graft intrasurgically, respectively. Ramus
      cortical was significantly thicker than the symphysis cortical, 2.9 +/- 0.4 mm
      versus 2.19 mm +/- 0.4 mm (p < .0001, CI 95%: 0.45-1.03). CONCLUSION: The
      symphysis and rami are good harvesting sources to obtain dense corticocancellous
      bone. The significant volumetric CAD differences between the symphysis and ramus
      seem to balance out intrasurgically and may be due to the greater cortical bone
      volume at the ramus area. It is plausible to harvest an average of 7.70 cm(3)
      from the symphysis and rami alone. The use of a CAD software program can enhance
      surgical treatment planning prior to bone transplantation.

PMID- 23157652
TI  - Perceptual and response-related components of unilateral neglect may evolve
      independently of one another: evidence from five single-case studies.
AB  - The Milner Landmark Task allows the disentanglement of perceptual and response
      related components of unilateral neglect. If these two components reflect
      separate functional systems, then cases should be observed in which the two
      components evolve differently across time. To test this hypothesis we surveyed a
      continuous series of 21 right hemisphere stroke patients. Five patients from the
      sample were affected by unilateral neglect at the outset and could be submitted
      to repeated administrations of the Landmark task in the first weeks post stroke.
      Two versions of the task were used, Landmark-Manual and Landmark-Verbal,
      differing in the type of response required. Two patients showed independent
      changes in the perceptual and the response-related component of neglect, hence
      confirming the view of separate functional systems underlying them. Dissociations
      between the task versions were found, witnessing a role of the type of response.
      Unexpectedly, one patient showed an initial leftward deviation of the subjective
      midpoint of the stimulus line, which later reversed to a classical rightward
      deviation. We interpreted such a pattern in terms of co-existing "productive" and
      "negative" components of perceptual neglect.

PMID- 23157653
TI  - Monitoring the iodine status of pregnant women in the United States.

PMID- 23157654
TI  - TNF-alpha antagonists and nail psoriasis: an open, 24-week, prospective cohort
      study in adult patients with psoriasis.
AB  - INTRODUCTION: Treatment of nail psoriasis can be challenging and unsatisfactory.
      The aim of this study was to compare the efficacy of three different anti-TNF
      alpha agents on nail psoriasis in patients affected by psoriasis. MATERIALS AND
      METHODS: Seventy-two patients with nail psoriasis were evaluated in this open, 24
      weeks, prospective study. Patients were enrolled in three groups of treatment:
      adalimumab, etanercept or infliximab. Severity of nail psoriasis was assessed by
      the Nail Psoriasis Severity Index (NAPSI) at baseline, week 14, and 24. RESULTS:
      Sixty patients were included in the study. The mean NAPSI was 33.77. In the
      adalimumab group, the mean NAPSI score was 33.1 (+/- 14.9) at baseline, 21 (+/-
      8.91) at week 14 and 11.4 (+/- 4.6) at week 24 (p < 0.0002). In the etanercept
      group, the mean NAPSI was 34.8 (+/- 12.38) at baseline, 23.6 (+/- 10.43) at week
      14, and 10.6 (+/- 5.25) at week 24 (p < 0.0016). In the infliximab group, the
      mean NAPSI was 33.3 (+/- 9.76) at baseline, 14.9 (+/- 4.20) at week 14 (p <
      0.001) and 3.1 (+/- 3.27) at week 24 (p < 0.00001). At week 14 efficacy was
      higher in infliximab group compared to adalimumab and etanercept groups (p <
      0.05). CONCLUSIONS: Among the three agents, in the infliximab group a significant
      improvement in nail psoriasis was observed as early as week 14 of therapy whereas
      in the adalimumab and etanercept groups at week 24.

PMID- 23157655
TI  - Postictal generalized EEG suppression is not associated with periictal cardiac
      autonomic instability in people with convulsive seizures.
AB  - PURPOSE: Postictal generalized EEG suppression (PGES) seems to be a
      pathophysiologic hallmark in ictal recordings of sudden unexpected death in
      epilepsy (SUDEP). It has recently been suggested that presence and duration of
      PGES might be a predictor of SUDEP risk. Little is known about the etiology of
      PGES. METHODS: We conducted a retrospective case-control study in 50 people with
      convulsive seizures (CS) recorded on digital video-electroencephalography (EEG).
      One CS per individual was reviewed for presence and duration of PGES by two
      independent observers: Preictal and postictal heart rate (HR) (1 min before
      seizure onset and 1, 3, 5, 15, and 30 min after seizure end) and frequency domain
      measures of heart rate variability (HRV), including the ratio of low frequency
      (LF) versus high frequency (HF) power, were analyzed. The relationship between
      PGES and periictal autonomic changes was evaluated, as well as its association
      with several clinical variables. KEY FINDINGS: Thirty-seven individuals (74%)
      exhibited PGES and 13 (26%) did not. CS resulted in a significant increase of
      periictal HR and the LF/HF ratio. PGES was associated with neither periictal HR
      (mean HR difference between PGES+ and PGES- seizures: -2 beats per minute [bpm],
      95% confidence interval [CI] -10 to +6 bpm) nor HRV change. There was no
      association between the duration of PGES and periictal HR change. People with
      PGES were more likely to be asleep before seizure onset (odds ratio [OR] 4.7, 95%
      CI 1.2-18.3) and had a higher age of onset of epilepsy (median age 15 vs. 4
      years). SIGNIFICANCE: PGES was not associated with substantial changes in
      measures of cardiac autonomic instability but was more prevalent in CS arising
      from sleep.

PMID- 23157656
TI  - Biodegradation of ivory (natural apatite): possible involvement of fungal
      activity in biodeterioration of the Lewis Chessmen.
AB  - Fungal biodeterioration of ivory was investigated with in vitro inoculation of
      samples obtained from boar and walrus tusks with the fungi Aspergillus niger and
      Serpula himantioides, species of known geoactive abilities. A combination of
      light and scanning electron microscopy together with associated analytical
      techniques was used to characterize fungal interactions with the ivory, including
      changes in ivory composition, dissolution and tunnelling, and the formation of
      new biominerals. The research was aimed at providing further understanding of the
      potential roles of fungi in the colonization and deterioration of ivory in
      terrestrial environments, but also contributes to our knowledge regarding the
      possible origins of the surface damage observed on early medieval sculptures made
      largely from walrus tusks, referred to as 'the Lewis hoard of gaming pieces',
      that were presumably produced for playing chess. The experiments have shown that
      the possibility of damage to ivory being caused by fungi is realistic. Scanning
      electron microscopy revealed penetration of fungal hyphae within cracks in the
      walrus tusk that showed also widespread tunnelling by fungal hyphae as well as
      'fungal footprints' where the surface was etched as a consequence of mycelial
      colonization. Similar phenomena were observed with boar tusk ivory, while
      production of metabolites could lead to complete dissolution of the sample.
      Colonization of ivory and/or exposure to fungal activity lead to extensive
      secondary biomineral formation, and this was identified as calcium oxalate,
      mainly as the monohydrate, whewellite.

PMID- 23157657
TI  - Intracystic gadolinium-enhanced MRI in the evaluation of residual giant-cystic
      craniopharyngiomas in children: report of four cases.
AB  - Residual giant-cystic craniopharyngiomas are amenable to intracavitary bleomycin
      treatment. Radiologic identification of potential cyst leaks is of paramount for
      treatment decisions. This report describes our experience in the use of
      intracystic Gadolinium (Gd)-enhanced MR imaging to determine potential
      communications between the tumoral cysts and other intra-axial spaces in 4
      pediatric patients with residual giant-cystic craniopharyngiomas in whom
      intracavitary bleomycin treatment was planned after the injection of .1-.2 mL of
      gadopentetate dimeglumine (Gd-DTPA). In three cases no leaks were found. In one
      case, whose previous water-soluble iodinated contrast-enhanced CT cystography was
      negative for leaks, intracystic Gd-enhanced MR showed intraventricular Gd
      enhancement. We conclude that MR imaging after intracystic administration of Gd
      based contrast paramagnetic agents is useful in the detection of potential leaks
      in cases of giant residual craniopharyngiomas. 

PMID- 23157658
TI  - Histamine suppresses epidermal keratinocyte differentiation and impairs skin
      barrier function in a human skin model.
AB  - BACKGROUND: Defects in keratinocyte differentiation and skin barrier are
      important features of inflammatory skin diseases like atopic dermatitis. Mast
      cells and their main mediator histamine are abundant in inflamed skin and thus
      may contribute to disease pathogenesis. METHODS: Human primary keratinocytes were
      cultured under differentiation-promoting conditions in the presence and absence
      of histamine, histamine receptor agonists and antagonists. The expression of
      differentiation-associated genes and epidermal junction proteins was quantified
      by real-time PCR, Western blot, and immunofluorescence labeling. The barrier
      function of human skin models was tested by the application of biotin as tracer
      molecule. RESULTS: The addition of histamine to human keratinocyte cultures and
      organotypic skin models reduced the expression of the differentiation-associated
      proteins keratin 1/10, filaggrin, and loricrin by 80-95%. Moreover, the addition
      of histamine to skin models resulted in the loss of the granular layer and
      thinning of the epidermis and stratum corneum by 50%. The histamine receptor H1R
      agonist, 2-pyridylethylamine, suppressed keratinocyte differentiation to the same
      extent as did histamine. Correspondingly, cetirizine, an antagonist of H1R,
      virtually abrogated the effect of histamine. The expression of tight junction
      proteins zona occludens-1, occludin, claudin-1, and claudin-4, as well as that of
      desmosomal junction proteins corneodesmosin and desmoglein-1, was down-regulated
      by histamine. The tracer molecule biotin readily penetrated the tight junction
      barrier of skin cultures grown in the presence of histamine, while their
      diffusion was completely blocked in nontreated controls. CONCLUSIONS: Our
      findings suggest a new mechanism by which mast cell activation and histamine
      release contribute to skin barrier defects in inflammatory skin diseases.

PMID- 23157659
TI  - Proteomic analysis of the royal jelly and characterization of the functions of
      its derivation glands in the honeybee.
AB  - To identify candidate royal jelly (RJ) proteins that might affect the physiologic
      status of honeybee colony members, we used shotgun proteomics to comprehensively
      identify the RJ proteome as well as proteomes of the hypopharyngeal gland (HpG),
      postcerebral gland (PcG), and thoracic gland (TG), from which RJ proteins are
      assumed to be derived. We identified a total of 38 nonredundant RJ proteins,
      including 22 putative secretory proteins and Insulin-like growth factor-binding
      protein complex acid labile subunit. Among them, 9 proteins were newly identified
      from RJ. Comparison of the RJ proteome with the HpG, PcG, and TG proteomes
      revealed that 17 of the 22 putative secretory RJ proteins were derived from some
      of these glands, suggesting that the RJ proteome is a cocktail of proteins from
      these three glands. Furthermore, pathway analysis suggested that the HpG proteome
      represents the molecular basis of the extremely high protein-synthesizing
      ability, whereas the PcG proteome suggests that the PcG functions as a reservoir
      for the volatile compounds and a primer pheromone. Finally, to further
      characterize the possible total RJ proteome, we identified putative secretory
      proteins in the proteomes of these three glands. This will be useful for
      predicting novel RJ protein components in future studies.

PMID- 23157660
TI  - The effect of propofol on patient reaction time and its relationship with loss of
      verbal contact before induction of anaesthesia.
AB  - Increasing the calculated plasma concentration of propofol has been shown to
      increase choice reaction time and visual and auditory response times. We studied
      the relationship of reaction to a vibrating handset as the effect-site target
      controlled propofol concentration was incrementally increased in 20 patients
      during sedation, before induction of general anaesthesia. The reaction time
      increased, initially slowly and then more rapidly, as the calculated effect-site
      concentration of propofol increased, until the reaction to the vibrating handset
      was lost at a mean (SD) propofol effect-site concentration of 2.0 (0.6) MUg.ml(
      1) . The loss of response to verbal contact occurred at a propofol effect-site
      concentration of 2.4 (0.5) MUg.ml(-1) . Reaction time may be of use clinically to
      warn of impending loss of verbal contact.

PMID- 23157662
TI  - Probing local hydrogen impurities in quasi-free-standing graphene.
AB  - We report high-resolution scanning tunneling microscopy and spectroscopy of
      hydrogenated, quasi-free-standing graphene. For this material, theory has
      predicted the appearance of a midgap state at the Fermi level, and first angle
      resolved photoemission spectroscopy (ARPES) studies have provided evidence for
      the existence of this state in the long-range electronic structure. However, the
      spatial extension of H defects, their preferential adsorption patterns on
      graphene, or local electronic structure are experimentally still largely
      unexplored. Here, we investigate the shapes and local electronic structure of H
      impurities that go with the aforementioned midgap state observed in ARPES. Our
      measurements of the local density of states at hydrogenated patches of graphene
      reveal a hydrogen impurity state near the Fermi level whose shape depends on the
      tip position with respect to the center of a patch. In the low H concentration
      regime, we further observe predominantly single hydrogenation sites as well as
      extended multiple C-H sites in parallel orientation to the lattice vectors,
      indicating an adsorption at the same graphene sublattice. This is corroborated by
      ARPES measurements showing the formation of a dispersionless hydrogen impurity
      state which is extended over the whole Brillouin zone.

PMID- 23157661
TI  - Pro-life role for c-Jun N-terminal kinase and p38 mitogen-activated protein
      kinase at rostral ventrolateral medulla in experimental brain stem death.
AB  - BACKGROUND: Based on an experimental brain stem death model, we demonstrated
      previously that activation of the mitogen-activated protein kinase kinase 1/2
      (MEK1/2)/extracellular signal-regulated kinase 1/2 (ERK1/2)/ mitogen-activated
      protein kinase signal-interacting kinase 1/2 (MNK1/2) cascade plays a pro-life
      role in the rostral ventrolateral medulla (RVLM), the origin of a life-and-death
      signal detected from systemic arterial pressure, which sequentially increases
      (pro-life) and decreases (pro-death) to reflect progressive dysfunction of
      central cardiovascular regulation during the advancement towards brain stem death
      in critically ill patients. The present study assessed the hypothesis that, in
      addition to ERK1/2, c-Jun NH2-terminal kinase (JNK) and p38 mitogen-activated
      protein kinase (p38MAPK), the other two mammalian members of MAPKs that are
      originally identified as stress-activated protein kinases, are activated
      specifically by MAPK kinase 4 (MAP2K4) or MAP2K6 and play a pro-life role in RVLM
      during experimental brain stem death. We further delineated the participation of
      phosphorylating activating transcriptional factor-2 (ATF-2) and c-Jun, the
      classical transcription factor activated by JNK or p38MAPK, in this process.
      RESULTS: An experimental model of brain stem death that employed microinjection
      of the organophosphate insecticide mevinphos (Mev; 10 nmol) bilaterally into RVLM
      of Sprague-Dawley rats was used, alongside cardiovascular, pharmacological and
      biochemical evaluations. Results from ELISA showed that whereas the total JNK,
      p38MAPK, MAP2K4 and MAP2K6 were not affected, augmented phosphorylation of JNK at
      Thr183 and Tyr185 and p38MAPK at Thr180 and Tyr182, accompanied by
      phosphorylation of their upstream activators MAP2K4 at Ser257 and Thr261 and
      MAP2K6 at Ser207 and Thr211 in RVLM occurred preferentially during the pro-life
      phase of experimental brain stem death. Moreover, the activity of transcription
      factors ATF-2 at Thr71 and c-Jun at Ser73, rather than Elk-1 at Ser383 in RVLM
      were also augmented during the pro-life phase. Furthermore, pretreatment by
      microinjection into the bilateral RVLM of specific JNK inhibitors, JNK inhibitor
      I (100 pmol) or SP600125 (5 pmol), or specific p38MAPK inhibitors, p38MAPK
      inhibitor III (500 pmol) or SB203580 (2 nmol), exacerbated the depressor effect
      and blunted the augmented life-and-death signal exhibited during the pro-life
      phase. On the other hand, pretreatment with the negative control for JNK or
      p38MAPK inhibitor, JNK inhibitor I negative control (100 pmol) or SB202474 (2
      nmol), was ineffective in the vehicle-controls and Mev-treatment groups.
      CONCLUSIONS: Our results demonstrated that activation of JNK or p38MAPK in RVLM
      by their upstream activators MAP2K4 or MAP2K6 plays a preferential pro-life role
      by sustaining the central cardiovascular regulatory machinery during experimental
      brain stem death via phosphorylation and activation of nuclear transcription
      factor ATF-2 or c-Jun.

PMID- 23157664
TI  - Directional telomeric silencing and lack of canonical B1 elements in two silencer
      Autonomously Replicating Sequences in S. cerevisiae.
AB  - BACKGROUND: Autonomously Replicating Sequences (ARS) in S. cerevisiae serve as
      origins of DNA replication or as components of cis-acting silencers, which impose
      positional repression at the mating type loci and at the telomeres. Both types of
      ARS can act as replicators or silencers, however it is not clear how these quite
      diverse functions are executed. It is believed that all ARS contain a core module
      of an essential ARS Consensus Sequence (ACS) and a non-essential B1 element.
      RESULTS: We have tested how the B1 elements contribute to the silencer and
      replicator function of ARS. We report that the ACS-B1 orientation of ARS has a
      profound effect on the levels of gene silencing at telomeres. We also report that
      the destruction of the canonical B1 elements in two silencer ARS (ARS317 and
      ARS319) has no effect on their silencer and replicator activity. CONCLUSIONS: The
      observed orientation effects on gene silencing suggest that ARSs can act as both
      proto-silencers and as insulator elements. In addition, the lack of B1 suggests
      that the ACS-B1 module could be different in silencer and replicator ARS.

PMID- 23157665
TI  - Reliability of the Norwegian version of the Children's Assessment of
      Participation and Enjoyment (CAPE) and Preferences for Activities of Children
      (PAC).
AB  - This study examined test-retest reliability of the Norwegian version of
      Children's Assessment of Participation and Enjoyment (CAPE), and Preferences for
      Activities of Children (PAC) in children with and without disabilities. Totally
      141 children, 107 typically developing, mean age 11.1, and 34 with disabilities,
      mean age 14.2 years participated. A cross-sectional, test-retest design was
      applied. The participants completed CAPE and PAC twice within mean 19 days.
      Reliability was examined by Chronbach's alpha, intraclass correlation
      coefficients (ICC), and Kappa statistics. The alpha values for internal
      consistency varied between 0.53 and 0.87 for the CAPE and between 0.75 and 0.93
      for the PAC. ICC coefficients varied from 0.49 to 0.83 for the CAPE and 0.50 to
      0.85 for the PAC. Kappa coefficients varied from 0.30 to 0.66. The Norwegian CAPE
      and PAC demonstrated sufficient measurement properties of internal consistency
      and test-retest reliability. The reliability of the CAPE, however, was not
      entirely satisfactory.

PMID- 23157666
TI  - Mercury biomagnification in marine zooplankton food webs in Hudson Bay.
AB  - While much research has been carried out on mercury in large marine mammals and
      associated food webs in northern regions, comparatively less has been conducted
      on lower trophic levels including zooplankton and the subsequent transfer to
      predators, which marks the entry of mercury into northern marine food webs. We
      present here the first database for mercury uptake and transfer exclusively
      within zooplankton food webs in northern marine waters. We have investigated both
      total (THg) and monomethylmercury (MMHg) concentrations, and isotopic signatures
      (delta(15)N and delta(13)C) in individual zooplankton taxa collected over a
      period of eight years (2003-2010) from across Hudson Bay (including Hudson Strait
      and Foxe Basin) as part of research icebreaker cruises. delta(15)N values ranged
      from 3.4 to 14.00/00, implying trophic levels ranging from 1 to 4, and THg
      concentrations ranged from 5 to 242 ng g(-1) dw. Food web linkages were
      identified within the data set, and mercury biomagnification was evident both
      with THg and MMHg concentrations increasing from prey to predator, and with
      trophic magnification factors (TMFs). Total mercury and MMHg transfer in a unique
      prey-predator linkage (Limacina helicina-Clione limacina) are investigated and
      discussed with regard to known physiological and biochemical characteristics. The
      results suggest that exposure to mercury at higher trophic levels including
      humans can be affected by processes at the bottom of Arctic marine food webs.

PMID- 23157667
TI  - Comparative effectiveness: beyond the buzz.

PMID- 23157669
TI  - Inappropriate elevation of serum thyrotropin levels in patients treated with
      axitinib.
AB  - BACKGROUND: Although anticancer treatment with the tyrosine kinase inhibitor
      (TKI) axitinib frequently causes thyroid dysfunction, the associated mechanism
      and clinical features have not been elucidated. METHODS: Six patients were
      treated with axitinib for metastatic renal cell carcinoma at the Hamamatsu
      University School of Medicine between 2008 and 2010. We reviewed their thyroid
      function results and compared them to those of patients treated with two other
      TKIs, sunitinib or sorafenib, and to those of subjects with normal hypothalamic
      pituitary-thyroid (HPT) function. RESULTS: Axitinib-induced thyroid dysfunction
      was observed in all patients, and two patterns were observed: increased serum
      thyrotropin (TSH) levels within one month after administration occurred in five
      patients and transient thyrotoxicosis due to destructive thyroiditis occurred in
      five patients within 7 months of treatment. Four patients exhibited both. When
      the relationship between the serum TSH and thyroid hormones was evaluated using
      plots of TSH versus both free thyroxine and free triiodothyronine, four patients
      showed an inappropriate elevation of serum TSH during administration of axitinib.
      Their values apparently shifted against the regression line compared to data from
      patients with a normal HPT function. A similar tendency, though weaker, was
      observed in some patients treated with sunitinib or sorafenib. CONCLUSION: This
      is the first study to report an inappropriate elevation of serum TSH levels in
      patients treated with axitinib.

PMID- 23157670
TI  - Rumination syndrome in children and adolescents: a school survey assessing
      prevalence and symptomatology.
AB  - BACKGROUND: Rumination syndrome (RS) is a functional gastrointestinal disorder
      (FGD) increasingly recognized in children and adolescents. The epidemiology of
      this condition in school aged children is poorly understood. The main objective
      of this study was to assess the prevalence of rumination and other related
      associations in a cohort of Sri Lankan children. METHODS: Children aged 10-16
      years were randomly selected from 8 schools in 4 provinces in Sri Lanka. RS was
      diagnosed using Rome III criteria. Data was collected using a self administered
      questionnaire distributed in an examination setting. It was translated into
      Sinhala, the native language and pretested before distribution. RESULTS: A total
      of 2163 children were included in the study (55% boys, mean age 13.4 years, SD
      1.8 years). Prevalence of RS was 5.1% (n = 110); boys 5.1% and girls 5.0%. When
      symptoms were analyzed, 73.6% reported re-swallowing of regurgitated food, while
      the rest spat it out. In 94.5% regurgitation occurred during the first hour after
      the meal. Only 8.2% had daily symptoms while 62.7% had symptoms weekly. Abdominal
      pain, bloating and weight loss were the commonest symptoms associated with RS
      (19.1%, 17.3% and 11.8% respectively). No significant association was observed
      between exposure to stressful events and rumination (p > 0.05). Twenty (18.2%)
      with RS fulfilled Rome III criteria for at least one other FGD. School
      absenteeism was seen in 11.8% of affected children. CONCLUSION: RS was reasonably
      common in this cohort of school-aged children and adolescents in Sri Lanka.
      However, symptoms were severe enough to affect schooling only in 12% of affected
      children. Around one fifth with RS had at least one other overlapping FGD.

PMID- 23157673
TI  - Predicting properties of organic optoelectronic materials: asymptotically
      corrected density functional study.
AB  - A practical computational procedure has been proposed that provides key
      electronic parameters of a polymer (fundamental bandgap, ionization energy,
      electron affinity, and intrachain electron and hole mobilities) determining its
      suitability as a donor or acceptor in organic optoelectronic materials. Series of
      oligomer calculations at the Becke3-Lee-Yang-Parr level with and without a self
      contained asymptotic correction using the 6-31G** basis set were performed. The
      bandgap, ionization energy, and electron affinities of a polymer are extrapolated
      from those of its oligomers obtained from the highest occupied and lowest
      unoccupied orbital energies in the Koopmans-like approximation. This scheme has
      been applied to conjugated polymers having the poly(p-phenylene),
      poly(thiophene), or poly(pyrrole) backbone as well as to PCBM. The observed
      values of the electronic parameters have been reproduced within less than 1 eV in
      most cases. With the predicted values of these parameters, estimates of the open
      circuit voltage and drift potential have been made for 22 valid donor-acceptor
      combinations. Several potentially useful combinations have been identified
      including the poly(thiophene):PCBM. The electron and hole mobilities have been
      found to correlate more strongly with the conformation (planarity) than the
      bandgap, but otherwise do not differ significantly.

PMID- 23157674
TI  - Simultaneous sinus lift and implant installation: prospective study of
      consecutive two hundred seventeen sinus lift and four hundred sixty-two implants.
AB  - PURPOSE: If less than 4 mm of residual bone is remained in posterior maxilla, two
      stage operation is recommended for implant installation. However, if primary
      stability could be obtained using tapered designed implants, one-stage surgery
      could be performed with reliable success rate in severely resorbed maxilla. The
      purpose of this prospective study was to evaluate survival and success rates of
      the implants simultaneously placed into grafted sinus using rough-surfaced
      implant. MATERIALS AND METHODS: A total of two hundred seventeen consecutive
      sinus lifting through lateral approach and four hundred sixty-two simultaneous
      implants were installed from November 2003 for 5.5 years. Xenogenic bone was used
      solely for bone graft materials. Second surgery was performed around 6 months
      after operation and porcelain fused metal or gold crown was used for definitive
      restorations. Cumulative survival and success rates were evaluated according to
      residual alveolar bone height (RABH), smoking status, and Schneiderian membrane
      perforation. RESULTS: The mean follow-up was 57.1 +/- 15.6 (36-98) months. Of the
      four hundred sixty-two implants, two hundred sixty-two implants (56.7%: group 1)
      were installed in posterior maxilla less than 4-mm RABH and two hundred implants
      (43.3%: group 2) were placed in over 5-mm RABH. The cumulative survival and
      success rates were 98.91% and 96.54%. There was no statistically significant
      difference in success rate between group 1 and group 2 (p = .3135). Perforation
      of the membrane was not related to success (p = .7162), but smoking status is
      significantly related with implant failure (p = .0003). CONCLUSIONS: Sinus
      lifting with simultaneous implant placement could be used to treat atrophic
      maxilla in patients with minimal RABH when initial stability could be obtained by
      using taper designed implants with surgical techniques. Smoking is a possible
      factor for implant failure. Membrane perforation did not have an adverse effect
      on implant success if the membrane was repaired with absorbable membrane and
      fibrin glue.

PMID- 23157675
TI  - Can spirometric norms be set using pre- or post- bronchodilator test results in
      older people?
AB  - BACKGROUND: Chronic Obstructive Pulmonary Disease (COPD) is defined by post
      bronchodilator spirometry. Data on "normal values" come predominantly from pre
      bronchodilator spirometry. The effects of this on diagnosis are unknown. METHODS:
      Lower limits of normal (LLN) were estimated from "normal" participants in the
      Burden of Obstructive Lung Disease (BOLD) programme. Values separately derived
      using pre- and post-bronchodilator spirometry were compared. Sensitivity and
      specificity of criteria derived from pre-bronchodilator spirometry and pre
      bronchodilator spirometry adjusted by a constant were assessed in the remaining
      population. The "gold standard" was the LLN for the post-bronchodilator
      spirometry in the "normal population". For FEV1/FVC, sensitivity and specificity
      of criteria were also assessed when a fixed value of < 70% was used rather than
      LLN. RESULTS: Of 6,600 participants with full data, 1,354 were defined as
      "normal". Mean differences between pre- and post- bronchodilator measurements
      were small and the Bland-Altman plots showed no association between difference
      and mean value. Compared with using the gold standard, however, tests using pre
      bronchodilator spirometry had a sensitivity and specificity of detecting a low
      FEV1 of 78.4% and 100%, a low FVC of 99.8% and 99.1% and a low FEV1/FVC ratio of
      65% and 100%. Adjusting this by a constant improved the sensitivity without
      substantially altering the specificity for FEV1 (99%, 99.8%), FVC (97.4%, 99.9%)
      and FEV1/FVC (98.7%, 99.5%). CONCLUSIONS: Using pre-bronchodilator spirometry to
      derive norms for lung function reduces sensitivity compared to a post
      bronchodilator gold standard. Adjustment of these values by a constant can
      improve validity of the test.

PMID- 23157676
TI  - Distinct functions of cis and trans phosphorylated tau in Alzheimer's disease and
      their therapeutic implications.
AB  - Proline-directed protein phosphorylation (pSer/Thr-Pro), a central signaling
      mechanism in diverse cellular processes in physiology and disease, has been
      proposed to be subject to further cis-trans conformational regulation by the
      unique prolyl isomerase Pin1. Until recently, no tool is available to directly
      detect the cis-trans conformation of Pin1-catalyzed cis-trans conformational
      changes in vivo. We have developed novel peptide chemistry that enables to
      generate the first antibodies that can distinguish cis from trans pThr231-Pro
      conformation in tau (p-tau). Using these conformation-specific antibodies, we
      have discovered that cis, but not trans, p-tau appears early in mild cognitive
      impairment (MCI) neurons and further accumulates in neurofibrillary degenerated
      neurons as Alzheimer's disease (AD) progresses, localizing to the dystrophic
      neurites, an early hallmark change that correlates with synaptic and cognitive
      deficits. Unlike trans p-tau, the cis not only cannot promote microtubule
      assembly, but also is more resistant to dephosphorylation and degradation, and
      prone to aggregation. Pin1 accelerates cis to trans conversion to prevent the
      accumulation of the pathogenic cis p-tau conformation in AD, providing the first
      structural evidence for how Pin1 protects against AD. These findings develop the
      first tool to directly detect cis-trans prolyl isomerization, especially after
      phosphorylation and uncover cis p-tau as the very early pathogenic conformation
      leading to tau pathology and memory loss in AD. These results also suggest novel
      conformation-specific diagnoses and therapies for AD and likely others. 

PMID- 23157677
TI  - The non-canonical IkappaB kinases IKKepsilon and TBK1 as potential targets for
      the development of novel therapeutic drugs.
AB  - IkappaB kinase epsilon (IKKepsilon) and TANK-binding kinase 1 (TBK1) are two non
      canonical IKKs which are involved in interferon regulatory factor (IRF) as well
      as nuclear factor kappaB (NF-kappaB) signaling cascades. Both kinases have
      already been linked to the pathophysiology of several diseases and therefore been
      suggested as potential promising targets for the development of therapeutic
      drugs. In this review, we summarize the roles of IKKepsilon and TBK1 in different
      diseases and outline therapeutic options for modulation of these kinases. 

PMID- 23157678
TI  - Understanding respiratory syncytial virus infection to improve treatment and
      immunity.
AB  - Despite significant research since it was discovered more than 50 years ago,
      respiratory syncytial virus (RSV) continues to be the leading agent causing
      infant hospitalization and respiratory distress worldwide. Although RSV normally
      does not cause mortality, this virus is recognized as a major public health and
      economic burden around the globe. RSV can modulate host immunity leading to an
      inflammatory response that produces lung damage and virus dissemination in the
      host airways. Remarkably, infection with the virus elicits poor immunity that in
      most cases fails to protect against subsequent exposures. Here, we review
      advances made on the understanding of the lifecycle of the virus, some of the
      molecular mechanisms it has evolved to cause pathology and ineffective immunity
      during infection. Hopefully, ongoing research will contribute to developing new
      drugs and candidate vaccines that will decrease the health burden caused by this
      virus. 

PMID- 23157679
TI  - Chemoprevention gene therapy (CGT): novel combinatorial approach for preventing
      and treating pancreatic cancer.
AB  - Pancreatic cancer remains one of the deadliest of all cancers despite aggressive
      surgical treatment combined with adjuvant radiotherapy and chemotherapy.
      Chemoresistance and radioresistance are the principal causes of failure of
      pancreatic cancer patients to respond to therapy. Conditionally replication
      competent adenovirus (CRCA)-based cancer gene therapy is an innovative strategy
      for treating cancers displaying inherent resistance to treatment. Limitations of
      current adenovirus (Ad)-based gene therapies for malignant tumors include lack of
      cancer-specificity, and effective and targeted delivery. To remedy this
      situation, CRCAs have been designed that express E1A, necessary for Ad
      replication, under the control of a cancer-specific progression elevated gene-3
      promoter (PEG-Prom) with concomitant expression of an immunomodulatory cytokine,
      such as mda-7/IL-24 or interferon-gamma (IFN-gamma), under the control of a
      ubiquitous and strong cytomegalovirus promoter (CMV-Prom) from the E3 region.
      These bipartite CRCAs, when armed with a transgene, are called cancer terminator
      viruses (CTVs), i.e., Ad.PEG-E1A-CMV-mda-7 (CTV-M7) and Ad.PEG-E1A-CMV-IFN-gamma
      (CTV-gamma), because of their universal effectiveness in cancer treatment
      irrespective of p53/pRb/p16 or other genetic alterations in tumor cells. In
      addition to their selective oncolytic effects in tumor cells, the potent
      'bystander antitumor' properties of MDA-7/IL-24 and IFN-gamma embody the CTVs
      with expanded treatment properties for both primary and distant cancers.
      Pancreatic cancer cells display a "translational block" of mda-7/IL-24 mRNA,
      limiting production of MDA-7/IL-24 protein and cancer-specific apoptosis.
      Specific chemopreventive agents abrogate this "translational block" resulting in
      pancreatic cancer-specific killing. This novel chemoprevention gene therapy (CGT)
      strategy holds promise for both prevention and treatment of pancreatic cancers
      where all other strategies have proven ineffective. 

PMID- 23157680
TI  - Enhanced antibiotic multi-resistance in nasal and faecal bacteria after
      agricultural use of streptomycin.
AB  - Streptomycin is used in arboriculture to control fire blight. Using sheep as a
      model, multidrug-resistant bacteria in mammals were found to be selected after
      the intentional release of streptomycin into the environment. Escherichia coli
      and Staphylococcus spp. were isolated from the faeces and nasal cavities,
      respectively, of sheep grazing on a field sprayed with streptomycin at
      concentrations used in orchards (test group) and on a field without streptomycin
      (control group). Before the application of streptomycin, the percentage of
      streptomycin-resistant E. coli isolates in faeces was 15.8% in the control group
      and 14.7% in the test group. After the application of streptomycin, the overall
      number of streptomycin-resistant E. coli isolates was significantly higher in the
      test group (39.9%) than in the control group (22.3%). Streptomycin-resistant
      Staphylococcus isolates were only detected after the application of streptomycin.
      Streptomycin resistance was frequently associated with resistance to
      sulfamethoxazole, ampicillin, tetracycline and chloramphenicol and less
      frequently to cefotaxime in E. coli, and to tetracycline, fusidic acid and
      tiamulin in Staphylococcus spp. This study shows that the application of low
      concentrations of streptomycin on grass, as occurs during the spraying of
      orchards, selects for multidrug-resistant nasal and enteric bacterial flora,
      including extended-spectrum beta-lactamase-producing E. coli.

PMID- 23157681
TI  - Sorafenib and dacarbazine in soft tissue sarcoma: a single institution
      experience.
AB  - BACKGROUND: To report on the anti-tumour activity and toxicity of sorafenib
      combined with dacarbazine in patients with pre-treated advanced soft tissue
      sarcoma (STSs). METHODS: From November 2009 to December 2010, 17 patients
      affected by STSs who had failed two or more regimen of chemotherapy, with a
      performance status <= 2 and measurable disease were consecutively enrolled in the
      present case series. Sorafenib was administered at 400 mg b.i.d. continuous
      dosing in combination with dacarbazine, 300 mg/m(2) for three consecutive days
      every 21 days until disease progression or intolerable toxicity. RESULTS:
      Fourteen patients were evaluable for response. Three patients stopped treatment
      early and were not evaluable for response. One of them died for not disease
      dependent reason, the other two went off-study due to rapid clinical worsening,
      without performing radiologic evaluation. No complete responses were registered.
      As by RECIST, partial responses (PR) were observed in three patients (21%),
      stable disease (SD) in six patients (43%) and progressive disease (PD) in five
      patients (36%), with a clinical benefit rate (RECIST PR+SD > 6 months) of 64%.
      The median time of progression was 20 weeks (range: 9 - 34 weeks) and the median
      overall survival was 43 weeks (range: 17 - 65 weeks). The main toxicities were
      neutropenia (36%), thrombocytopenia (36%), hypertension (36%), fatigue (50%) and
      skin reactions (57%). Five patients required dose reductions (both dacarbazine
      and sorafenib) for toxicity and three patients required only sorafenib reduction
      for dermatologic reactions. One patient was taken off-study because of severe
      sorafenib-related dermatologic toxicity. CONCLUSIONS: Sorafenib and dacarbazine
      combination seems to be an active and safety regimen in pre-treated STSs. A Phase
      II trial is ongoing in patient affected by selected sarcoma subtypes.

PMID- 23157682
TI  - Local receptor revision and class switching to IgE in chronic rhinosinusitis with
      nasal polyps.
AB  - BACKGROUND: Chronic rhinosinusitis with nasal polyps (NP) and allergic rhinitis
      (AR) is characterized by local Th2 inflammation and up-regulation of IgE;
      however, IgE in NP is 'polyclonal' and allergen specific, whereas IgE in AR is
      'oligoclonal' and allergen specific. Germinal center (GC) reactions occur in AR,
      while only the formation of GC-like structures in NP is described. The aim of
      this study was to investigate the involvement of local IgE production, class
      switch recombination, and receptor revision in NP. METHODS: We compared the
      levels of local IgE, germline gene transcripts, and mature Ig mRNA expression,
      recombination activating gene (RAG1 and RAG2), key markers of Th2 inflammation,
      and GC reactions in NP tissue vs AR and control tissue. Nasal mucosa was
      immunostained for the co-expression of RAG1 and RAG2 in B cells, plasma cells,
      and T cells, using dual or triple immunofluorescence (IF). RESULTS: In NP, local
      IgE level and key markers of local class switching are increased compared with AR
      and normal controls (NC). In NP, switch circle transcripts reveal ongoing local
      class switch recombination to IgE. Up to 30% of B cells, plasma cells, and T
      cells in nasal polyps re-express both RAG1 and RAG2, required for receptor
      revision. RAG1 and RAG2 mRNA concentrations are increased in NP and correlated
      with the magnitude of inflammation and the presence of S. aureus enterotoxin
      (superantigen)-specific IgE in the nasal polyp mucosa. CONCLUSION: Our results
      provide the first evidence of local receptor revision and class switching to IgE,
      and B-cell differentiation into IgE-secreting plasma cells in NP.

PMID- 23157683
TI  - OnabotulinumtoxinA unmasking myasthenia gravis.

PMID- 23157684
TI  - Photochemical trans-/cis-isomerization and quantitation of zearalenone in edible
      oils.
AB  - The emphasis of the present work was to investigate the photochemical conversion
      of trans- to cis-zearalenone in edible oils under real-life conditions. For
      quantitation purposes a cis-zearalenone standard was synthesized and
      characterized for its identity and purity (>=95%) by (1)H NMR, X-ray
      crystallography, HPLC fluorescence and mass spectrometric detection. In a sample
      survey of 12 edible oils (9 corn oils, 3 hempseed oils) from local supermarkets
      all corn oils contained trans-zearalenone (median 194 MUg/kg), but no cis
      zearalenone was detected. For alteration studies trans-zearalenone contaminated
      corn oils were exposed to sunlight over 4 and 30 weeks, revealing an obvious
      shift toward cis-zearalenone up to a cis/trans ratio of 9:1 by storage in
      colorless glass bottles. Irradiation experiments of trans-zearalenone in
      different organic solvents confirmed the preferred formation of cis-zearalenone
      possibly caused by entropic effects rather than by enthalpic entities as
      investigated by quantum chemical and classical force field simulations.

PMID- 23157685
TI  - Elasticity of an assembly of disordered nanoparticles interacting via either van
      der Waals-bonded or covalent-bonded coating layers.
AB  - Tailoring physical and chemical properties at the nanoscale by assembling
      nanoparticles currently paves the way for new functional materials. Obtaining the
      desired macroscopic properties is usually determined by a perfect control of the
      contact between nanoparticles. Therefore, the physics and chemistry of
      nanocontacts are one of the central issues for the design of the nanocomposites.
      Since the birth of atomic force microscopy, crucial advances have been achieved
      in the quantitative evaluation of van der Waals and Casimir forces in
      nanostructures and of adhesion between the nanoparticles. We present here an
      investigation, by a noncontact method, of the elasticity of an assembly of
      nanoparticles interacting via either van der Waals-bonded or covalent-bonded
      coating layers. We demonstrate indeed that the ultrafast opto-acoustic technique,
      based on the generation and detection of hypersound by femtosecond laser pulses,
      is very sensitive to probe the properties of the nanocontacts. In particular, we
      observe and evaluate how much the subnanometric molecules present at nanocontacts
      influence the coherent acoustic phonon propagation along the network of the
      interconnected silica nanoparticles. Finally, we show that this ultrafast opto
      acoustic technique provides quantitative estimates of the rigidity/stiffness of
      the nanocontacts.

PMID- 23157686
TI  - The radical-binding lipocalin A1M binds to a Complex I subunit and protects
      mitochondrial structure and function.
AB  - AIMS: During cell death, energy-consuming cell degradation and recycling programs
      are performed. Maintenance of energy delivery during cell death is therefore
      crucial, but the mechanisms to keep the mitochondrial functions intact during
      these processes are poorly understood. We have investigated the hypothesis that
      the heme- and radical-binding ubiquitous protein alpha1-microglobulin (A1M) is
      involved in protection of the mitochondria against oxidative insult during cell
      death. RESULTS: Using blood cells, keratinocytes, and liver cells, we show that
      A1M binds with high affinity to apoptosis-induced cells and is localized to
      mitochondria. The mitochondrial Complex I subunit NDUFAB1 was identified as a
      major molecular target of the A1M binding. Furthermore, A1M was shown to inhibit
      the swelling of mitochondria, and to reverse the severely abrogated ATP
      production of mitochondria when exposed to heme and reactive oxygen species
      (ROS). INNOVATION: Import of the radical- and heme-binding protein A1M from the
      extracellular compartment confers protection of the mitochondrial structure and
      function during cellular insult. CONCLUSION: A1M binds to a subunit of Complex I
      and has a role in assisting the mitochondria to maintain its energy delivery
      during cell death. A1M may also, at the same time, counteract and eliminate the
      ROS generated by the mitochondrial respiration to prevent oxidative damage to
      surrounding healthy tissue.

PMID- 23157688
TI  - Investigation of surfactant mediated acid-base charging of mineral oxide
      particles dispersed in apolar systems.
AB  - The current work examines the role of acid-base properties on particle charging
      in apolar media. Manipulating the polarity and magnitude of charge in such
      systems is of growing interest to a number of applications. A major hurdle to the
      implementation of this technology is that the mechanism(s) of particle charging
      remain a subject of debate. The authors previously conducted a study of the
      charging of a series of mineral oxide particles dispersed in apolar systems that
      contained the surfactant AOT. It was observed that there was a correlation
      between the particle electrophoretic mobility and the acid-base nature of the
      particle, as characterized by aqueous point of zero charge (PZC) or the
      isoelectric point (IEP). The current study investigates whether or not a similar
      correlation is observed with other surfactants, namely, the acidic Span 80 and
      the basic OLOA 11000. This is accomplished by measuring the electrophoretic
      mobility of a series of mineral oxides that are dispersed in Isopar-L containing
      various concentrations of either Span 80 or OLOA 11000. The mineral oxides used
      have PZC values that cover a wide range of pH, providing a systematic study of
      how particle and surfactant acid-base properties impact particle charge. It was
      found that the magnitude and polarity of particle surface charge varied linearly
      with the particle PZC for both surfactants used. In addition, the point at which
      the polarity of charge reversed for the basic surfactant OLOA 11000 was shifted
      to a pH of approximately 8.5, compared to the previous result of about 5 for AOT.
      This proves that both surfactant and particle acid-base properties are important,
      and provides support for the theory of acid-base charging in apolar media.

PMID- 23157689
TI  - Apolipoprotein M can discriminate HNF1A-MODY from Type 1 diabetes.
AB  - AIMS: Missed diagnosis of maturity-onset diabetes of the young (MODY) has led to
      an interest in biomarkers that enable efficient prioritization of patients for
      definitive molecular testing. Apolipoprotein M (apoM) was suggested as a
      biomarker for hepatocyte nuclear factor 1 alpha (HNF1A)-MODY because of its
      reduced expression in Hnf1a(-/-)  mice. However, subsequent human studies
      examining apoM as a biomarker have yielded conflicting results. We aimed to
      evaluate apoM as a biomarker for HNF1A-MODY using a highly specific and sensitive
      ELISA. METHODS: ApoM concentration was measured in subjects with HNF1A-MODY (n =
      69), Type 1 diabetes (n = 50), Type 2 diabetes (n = 120) and healthy control
      subjects (n = 100). The discriminative accuracy of apoM and of the apoM/HDL ratio
      for diabetes aetiology was evaluated. RESULTS: Mean (standard deviation) serum
      apoM concentration (MUmol/l) was significantly lower for subjects with HNF1A-MODY
      [0.86 (0.29)], than for those with Type 1 diabetes [1.37 (0.26), P = 3.1 * 10(
      18) ) and control subjects [1.34 (0.22), P = 7.2 * 10(-19) ). There was no
      significant difference in apoM concentration between subjects with HNF1A-MODY and
      Type 2 diabetes [0.89 (0.28), P = 0.13]. The C-statistic measure of
      discriminative accuracy for apoM was 0.91 for HNF1A-MODY vs. Type 1 diabetes,
      indicating high discriminative accuracy. The apoM/HDL ratio was significantly
      lower in HNF1A-MODY than other study groups. However, this ratio did not perform
      well in discriminating HNF1A-MODY from either Type 1 diabetes (C-statistic =
      0.79) or Type 2 diabetes (C-statistic = 0.68). CONCLUSIONS: We confirm an earlier
      report that serum apoM levels are lower in HNF1A-MODY than in controls. Serum
      apoM provides good discrimination between HNF1A-MODY and Type 1 diabetes and
      warrants further investigation for clinical utility in diabetes diagnostics.

PMID- 23157691
TI  - Intervention with feedback using Outcome Questionnaire 45 (OQ-45) in a Swedish
      psychiatric outpatient population. A randomized controlled trial.
AB  - AIM: The objective of the study was to evaluate the efficacy of the Outcome
      Questionnaire 45 (OQ-45) with feedback in a Swedish psychiatric outpatient
      population using a randomized controlled design. METHOD: In all 1720 patients
      made at least one regular visit to the clinics in the period 12 February 2007 to
      10 February 2008 and received information about the study. Of these, 374 patients
      (22%) agreed to participate. After written consent, 188 patients were randomized
      to the feedback group and 186 patients to the control group. Those constituted
      the intention-to-treat (ITT) group. Two hundred and sixty-two patients (70%)
      completed the OQ-45 questionnaire at least twice, and they were included in the
      per-protocol analysis. Those who improved less than expected and were at risk for
      treatment failure were called alerted patients. RESULTS: There was a tendency
      that patients who received feedback improved more than the controls in OQ-45
      total score. In the ITT analysis, the P-value was 0.061 and the effect size g =
      0.21. In the per-protocol analysis the P-value was 0.076 and the effect size g =
      0.24. In the intervention group, 27% of the patients were alerted because of risk
      of treatment failure vs. 28% in the control group (reaching level of alertness).
      The OQ-45 differences between the intervention and control groups did not
      significantly differ for patients who were alerted/reaching level of alertness
      and for non-alerted patients (g = 0.17 and g = 0.28, respectively). CONCLUSIONS:
      The feedback group had a tendency to improve more than the control group,
      possibly indicating that the method is effective, and the result (basically)
      supports previous findings.

PMID- 23157692
TI  - Review article: towards a considered and ethical approach to organ support in
      critically-ill patients with cirrhosis.
AB  - BACKGROUND: Increasing numbers of patients are being admitted to hospital with
      decompensated chronic liver disease in the UK. A significant proportion will
      develop complicating extra-hepatic organ dysfunction, but the selection of those
      who should be admitted to intensive care is complex and challenging. Alcohol
      related liver disease also presents complex ethical dilemmas. AIM: To review
      recent survival analyses and explore differences in secondary and tertiary care;
      to highlight strengths and weaknesses of prognostic models, therapeutic advances
      and shifts in prognostic expectation. We also aim to explore the ethical
      challenges presented by addiction and self-injury in an area of limited resource.
      METHODS: We searched PubMed for articles discussing 'cirrhosis', 'prognosis',
      'critical illness', 'organ failure', 'renal failure', 'alcohol', 'ethics' and
      'addiction'. We also explored particular ethical dilemmas encountered by the
      authors and colleagues. RESULTS: Prognosis has improved in many cirrhotic
      complications and historically poor outcomes in tertiary care may reflect a more
      complex patient cohort. Previously 'untreatable' complications are now being
      managed successfully. Estimates of survival are more accurate after a 48-h period
      of supportive care. Physicians are not best placed to make judgments with regard
      to deservingness, moral responsibility, rationing and access to organ support in
      cases of acute deterioration related to alcoholism, and the case for denying
      support must be made on purely medical grounds. CONCLUSIONS: An early, aggressive
      approach to organ support is justified. Further discussions between hepatologists
      and critical care physicians are required to determine acceptable burden-to
      benefit ratios for prolonged intensive care support in young alcoholic patients.

PMID- 23157693
TI  - Predicting intracranial hemorrhage after traumatic brain injury in low and middle
      income countries: a prognostic model based on a large, multi-center,
      international cohort.
AB  - BACKGROUND: Traumatic brain injury (TBI) affects approximately 10 million people
      annually, of which intracranial hemorrhage is a devastating sequelae, occurring
      in one-third to half of cases. Patients in low and middle-income countries (LMIC)
      are twice as likely to die following TBI as compared to those in high-income
      countries. Diagnostic capabilities and treatment options for intracranial
      hemorrhage are limited in LMIC as there are fewer computed tomography (CT)
      scanners and neurosurgeons per patient as in high-income countries. METHODS: The
      Medical Research Council CRASH-1 trial was utilized to build this model. The
      study cohort included all patients from LMIC who received a CT scan of the brain
      (n = 5669). Prognostic variables investigated included age, sex, time from injury
      to randomization, pupil reactivity, cause of injury, seizure and the presence of
      major extracranial injury. RESULTS: There were five predictors that were included
      in the final model; age, Glasgow Coma Scale, pupil reactivity, the presence of a
      major extracranial injury and time from injury to presentation. The model
      demonstrated good discrimination and excellent calibration (c-statistic 0.71). A
      simplified risk score was created for clinical settings to estimate the
      percentage risk of intracranial hemorrhage among TBI patients. CONCLUSION: Simple
      prognostic models can be used in LMIC to estimate the risk of intracranial
      hemorrhage among TBI patients. Combined with clinical judgment this may
      facilitate risk stratification, rapid transfer to higher levels of care and
      treatment in resource-poor settings.

PMID- 23157694
TI  - Modulation of interhemispheric interactions across symmetric and asymmetric
      bimanual force regulations.
AB  - The corpus callosum is essential for neural communication between the left and
      right hemispheres. Although spatiotemporal coordination of bimanual movements is
      mediated by the activity of the transcallosal circuit, it remains to be addressed
      how transcallosal neural activity is involved in the dynamic control of bimanual
      force execution in human. To address this issue, we investigated transcallosal
      inhibition (TCI) elicited by single-pulse transcranial magnetic stimulation (TMS)
      in association with the coordination condition of bimanual force regulation.
      During a visually-guided bimanual force tracking task, both thumbs were abducted
      either in-phase (symmetric condition) or 180 degrees  out-of-phase (asymmetric
      condition). TMS was applied to the left primary motor cortex to elicit the
      disturbance of ipsilateral left force tracking due to TCI. The tracking accuracy
      was equivalent between the two conditions, but the synchrony of the left and
      right tracking trajectories was higher in the symmetric condition than in the
      asymmetric condition. The magnitude of force disturbance and TCI were larger
      during the symmetric condition than during the asymmetric condition. Right
      unimanual force tracking influenced neither the force disturbance nor TCI during
      tonic left thumb abduction. Additionally, these TMS-induced ipsilateral motor
      disturbances only appeared when the TMS intensity was strong enough to excite the
      transcallosal circuit, irrespective of whether the crossed corticospinal tract
      was activated. These findings support the hypotheses that interhemispheric
      interactions between the motor cortices play an important role in modulating
      bimanual force coordination tasks, and that TCI is finely tuned depending on the
      coordination condition of bimanual force regulation.

PMID- 23157695
TI  - Cross validation of the b Test in a large known groups sample.
AB  - The b Test (Boone, Lu, & Herzberg, 2002a) is a measure of cognitive performance
      validity originally validated on 91 non-credible participants and 7 credible
      clinical comparison groups (total n = 161). The purpose of the current study was
      to provide cross-validation data for the b Test on a known groups sample of non
      credible participants (n = 212) and credible heterogeneous neuropsychological
      clinic patients (n = 103). The new data showed that while the original E-score
      cut-off of >= 155 achieved excellent specificity (99%), it was associated with
      relatively poor sensitivity (41%). However, the cut-off could be substantially
      lowered to >=82, while still maintaining adequate specificity (>=90%) and raising
      sensitivity to 68%. Examination of non-credible subgroups revealed that b Test
      sensitivity in feigned mild traumatic brain injury (mTBI) was 58%, whereas in non
      credible patients claiming depression and psychosis, cut-off sensitivity was 76%
      and 67%, respectively. These data suggest that the b Test may have a particular
      role in detection of non-credible cognitive symptoms associated with feigned
      psychiatric symptoms, and that fabricated deficits in processing speed and
      vigilance/visual scanning, detected by the b Test, are more prominent in feigned
      psychiatric presentations than in feigned mTBI. Further, b Test failures in
      patients with somatoform disorders were common, indicating that the b Test may
      have a specific use in detection of non-consciously created cognitive dysfunction
      associated with somatoform conditions.

PMID- 23157696
TI  - The promise of competency-based education in the health professions for improving
      global health.
AB  - Competency-based education (CBE) provides a useful alternative to time-based
      models for preparing health professionals and constructing educational programs.
      We describe the concept of 'competence' and 'competencies' as well as the
      critical curricular implications that derive from a focus on 'competence' rather
      than 'time'. These implications include: defining educational outcomes,
      developing individualized learning pathways, setting standards, and the
      centrality of valid assessment so as to reflect stakeholder priorities. We also
      highlight four challenges to implementing CBE: identifying the health needs of
      the community, defining competencies, developing self-regulated and flexible
      learning options, and assessing learners for competence. While CBE has been a
      prominent focus of educational reform in resource-rich countries, we believe it
      has even more potential to align educational programs with health system
      priorities in more resource-limited settings. Because CBE begins with a careful
      consideration of the competencies desired in the health professional workforce to
      address health care priorities, it provides a vehicle for integrating the health
      needs of the country with the values of the profession.

PMID- 23157697
TI  - Incidence and correlates of receiving cigarettes as gifts and selecting preferred
      brand because it was gifted: findings from the ITC China Survey.
AB  - BACKGROUND: Giving cigarettes as gifts is a common practice in China, but there
      have been few systematic studies of this practice. The present study was designed
      to estimate the incidence of receiving cigarettes as gifts, correlates of this
      practice, and its impact on brand selection in a representative sample of urban
      adult smokers in China. METHODS: Data were analyzed from Wave 2 of the
      International Tobacco Control (ITC) China Survey, where 4843 adult urban smokers
      were interviewed in six major Chinese cities between October 2007 and January
      2008. The incidence of most recent cigarette acquisition due to gifting and the
      prevalence of preferred brand selection due to having received it as a gift were
      estimated. Bivariate and adjusted logistic regression models were estimated to
      identify factors associated with these two outcomes. RESULTS: The incidence of
      receiving cigarettes as a gift at most recent cigarette acquisition was 3.5%.
      Smokers who received these gifted cigarettes were more likely to be female,
      older, have higher educational attainment, live in Beijing, and smoke fewer
      cigarettes per day. The prevalence of choosing one's preferred brand due to
      having received it as a gift was 7.0%, and this was more likely among smokers who
      lived in Beijing and Guangzhou, had lower educational attainment, smoked less
      frequently, and had smoked their preferred brand for less than one year.
      CONCLUSIONS: The 3.5% incidence of one's most recent cigarette acquisition due to
      gifting is consistent with prevalence estimates based on longer reference periods
      and translates into the average smoker receiving a gift of cigarettes
      approximately five times a year. Gifting also appears to have a significant
      influence on brand preference. Tobacco control interventions in China may need to
      denormalize the practice of giving cigarettes as gifts in order to decrease the
      social acceptability of smoking.

PMID- 23157698
TI  - The next frontier in composite tissue allotransplantation.
AB  - Solid organ transplantations became a clinical option in the 1950s. The hand
      allograft was the pioneer of composite tissue allotransplantation (CTA),
      successfully started near the end of the last century despite arguments over the
      practicality and methods. Since then, CTA such as hand and face has continued to
      progress from the theoretical to clinical reality. The treatment principles, drug
      combinations, and mechanisms of the immunosuppression medications on which
      contemporary transplant surgeries have been based continue to develop as
      researchers and physicians gain more experience in the CTA field. It could be
      argued that the ethical issues associated with CTA have prevented evolution of
      the field rather than surgical or technical skill. This is particularly true for
      allo-head and body reconstruction (AHBR). How can leaders in the field of CTA
      develop a model that would satisfy ethical concerns? Bolstered by recent
      successes in the field, is it time to traverse the next frontier? Can AHBR ever
      be a feasible option in the clinical setting? The reader will be provided with a
      brief history of CTA from theory to research to clinical practice. A concise
      description of AHBR as it pertains to the critical procedure (i.e., surgery
      design) will also be discussed.

PMID- 23157699
TI  - Post-metabolic response to passive normobaric hypoxic exposure in sedendary
      overweight males: a pilot study.
AB  - BACKGROUND: The present pilot study was designed to test the impact of passive
      acute normobaric hypoxic exposure (PAH) and passive short-term normobaric hypoxic
      exposure (PSH) conditions on energy expenditure (EE) and substrates utilisation
      (glucose and lipid oxidation). METHODS: Eleven participants have completed the
      PAH session while the control group (CG) underwent a simulated experimental
      condition in normobaric normoxic condition. A subset of 6 participants underwent
      an additional six 3-hour sessions on consecutive days. Metabolic rates were
      obtained pre- and post-treatments on the morning following an overnight (12
      hours) fast in PAH, PSH, and CG groups. RESULTS: The statistical outcomes showed
      a significant increase in EE for PAH, control, and PSH while a shift in substrate
      utilization towards lipid sources was only detected for PAH and PSH,
      respectively. CONCLUSION: This pilot study showed that passive acute normobaric
      hypoxic exposure did affect EE and fuel utilization in sedentary overweight males
      and that further passive normobaric hypoxic exposures (PSH) magnified these
      metabolic adjustments. These outcomes provide valuable information for further
      research in the area of hypoxia as a new therapeutic strategy to improve the
      management of weight loss.

PMID- 23157701
TI  - Low-temperature spectra of the analogues of 10-hydroxybenzo[h]quinoline as an
      indication of barrierless ESIPT.
AB  - The absorption and fluorescence spectra of two analogues of 10
      hydroxybenzo[h]quinoline (10-HBQ), namely, 1-hydroxy-7-methylbenzo[c]acridine
      (HMBA) and 4-hydroxybenzo[c]phenanthridine (HBPA), were studied in n-alkane
      matrices at 5 K. Considerable energy separation between the onsets of the spectra
      and broadening of the bands was an indication that intramolecular proton transfer
      (ESIPT) takes place at such a low temperature. DFT and ab initio methods were
      used to calculate the electronic transition energies and oscillator strengths and
      the vibronic structure of the electronic spectra. Shortcomings in our knowledge
      of the shape of the potential energy surface for ESIPT systems are highlighted in
      the context of the discussion of the shape of the electronic spectra. The pi
      expansion of the 10-HBQ chromophore achieved by adding a benzene moiety at
      various positions adjacent to the pyridine ring led to compounds possessing
      diverse photophysical properties, ranging from the non-ESIPT strongly fluorescent
      molecule of 10-hydroxy-1-azaperylene to weakly emitting (or nonemitting)
      molecules, where ESIPT occurs very efficiently.

PMID- 23157700
TI  - Gene expression analysis of a murine model with pulmonary vascular remodeling
      compared to end-stage IPAH lungs.
AB  - BACKGROUND: Idiopathic pulmonary arterial hypertension (IPAH) continues to be one
      of the most serious intractable diseases that might start with activation of
      several triggers representing the genetic susceptibility of a patient. To
      elucidate what essentially contributes to the onset and progression of IPAH, we
      investigated factors playing an important role in IPAH by searching discrepant or
      controversial expression patterns between our murine model and those previously
      published for human IPAH. We employed the mouse model, which induced
      muscularization of pulmonary artery leading to hypertension by repeated
      intratracheal injection of Stachybotrys chartarum, a member of nonpathogenic and
      ubiquitous fungus in our envelopment. METHODS: Microarray assays with ontology
      and pathway analyses were performed with the lungs of mice. A comparison was made
      of the expression patterns of biological pathways between our model and those
      published for IPAH. RESULTS: Some pathways in our model showed the same
      expression patterns in IPAH, which included bone morphogenetic protein (BMP)
      signaling with down-regulation of BMP receptor type 2, activin-like kinase type
      1, and endoglin. On the other hand, both Wnt/planar cell polarity (PCP) signaling
      and its downstream Rho/ROCK signaling were found alone to be activated in IPAH
      and not in our model. CONCLUSIONS: Activation of Wnt/PCP signaling, in upstream
      positions of the pathway, found alone in lungs from end stage IPAH may play
      essential roles in the pathogenesis of the disease.

PMID- 23157702
TI  - Daniel R. Mishell, Jr, MD, and the journal Contraception.

PMID- 23157703
TI  - Effect of exposure to ulipristal acetate on sperm function.
AB  - OBJECTIVE: A pill containing ulipristal acetate (UPA) is used for emergency
      contraception (EC). Considering that, following its intake, spermatozoa may be
      exposed to UPA in the female genital tract we intended to evaluate sperm
      functions after incubation with this compound. METHODS: Motile spermatozoa were
      selected by swim-up and were incubated under capacitating conditions with UPA (at
      concentrations of 1, 10, 100, 1,000, and 10,000 ng/ml) or control medium. The
      main outcome measures were sperm vitality, sperm protein tyrosine phosphorylation
      (TyrP), spontaneous acrosomal reaction (AR), and human follicular fluid (hFF)
      induced AR. RESULTS: Sperm vitality and TyrP pattern were similar between
      spermatozoa exposed to UPA or control. In addition, spontaneous AR ranged from
      14.0 +/-1.5% to 18.0 +/-1.9% after exposure to UPA or control medium without
      significant differences, and UPA did not prevent hFF-induced AR. CONCLUSIONS:
      Incubation of sperm with UPA at concentrations around the expected plasma levels
      after ingestion of this EC pill (~100-200 ng/ml) did not modify the signal
      transduction of TyrP involved in sperm capacitation. Moreover, UPA showed no
      agonist effect on progesterone receptors because it did not induce AR.
      Considering that progesterone in hFF is essential for AR induction, and UPA did
      not prevent the hFF-induced AR, an antagonist action of UPA on the AR is
      unlikely.

PMID- 23157704
TI  - Attitudes towards motherhood and fertility awareness among 20-40-year-old female
      healthcare professionals.
AB  - OBJECTIVE: To explore attitudes towards family formation and fertility awareness
      among Danish female healthcare professionals. METHODS: We collected cross
      sectional baseline data from a prospective cohort study of 863 women, ranging in
      age from 20 to 40 years, working at a hospital in Denmark. Information about
      participants' intentions and attitudes towards family formation and fertility
      knowledge was gathered by means of a questionnaire. RESULTS: Only 2% of the
      respondents did not want children. Most women believed that motherhood is
      important, and hoped to have two to three children. About half of the respondents
      intended to have their last child after the age of 35 years. The most important
      prerequisites for family formation included: living in a stable relationship,
      having completed one's studies, a sound financial situation, a job that can be
      kept when having children, access to public child day care, and the possibility
      of travelling. As many as 50% of women underrated the impact of a woman's age on
      fertility, and overestimated the success rates of assisted reproductive
      technology (ART) treatments. CONCLUSIONS: Many female healthcare professionals
      contemplated giving birth after the age of 35 years. Knowledge of fertility and
      ART success rates is needed to make well-informed decisions about when to have
      children.

PMID- 23157705
TI  - Fungal oxidative dissolution of the Mn(II)-bearing mineral rhodochrosite and the
      role of metabolites in manganese oxide formation.
AB  - Microbially mediated oxidation of Mn(II) to Mn(III/IV) oxides influences the
      cycling of metals and remineralization of carbon. Despite the prevalence of
      Mn(II)-bearing minerals in nature, little is known regarding the ability of
      microbes to oxidize mineral-hosted Mn(II). Here, we explored oxidation of the
      Mn(II)-bearing mineral rhodochrosite (MnCO3 ) and characteristics of ensuing Mn
      oxides by six Mn(II)-oxidizing Ascomycete fungi. All fungal species substantially
      enhanced rhodochrosite dissolution and surface modification. Mineral-hosted
      Mn(II) was oxidized resulting in formation of Mn(III/IV) oxides that were all
      similar to delta-MnO2 but varied in morphology and distribution in relation to
      cellular structures and the MnCO3 surface. For four fungi, Mn(II) oxidation
      occurred along hyphae, likely mediated by cell wall-associated proteins. For two
      species, Mn(II) oxidation occurred via reaction with fungal-derived superoxide
      produced at hyphal tips. This pathway ultimately resulted in structurally unique
      Mn oxide clusters formed at substantial distances from any cellular structure.
      Taken together, findings for these two fungi strongly point to a role for fungal
      derived organic molecules in Mn(III) complexation and Mn oxide templation.
      Overall, this study illustrates the importance of fungi in rhodochrosite
      dissolution, extends the relevance of biogenic superoxide-based Mn(II) oxidation
      and highlights the potential role of mycogenic exudates in directing mineral
      precipitation.

PMID- 23157706
TI  - Significance of the amide functionality on DOPA-based monolayers on gold.
AB  - The adhesive proteins secreted by marine mussels contain an unusual amino acid,
      3,4-dihydroxyphenylalanine (DOPA), that is responsible for the cohesive and
      adhesive strength of this natural glue and gives mussels the ability to attach
      themselves to rocks, metals, and plastics. Here we report a detailed structural
      and spectroscopic investigation of the interface between N-stearoyldopamine and a
      single-crystalline Au(111) model surface and an amide-absent molecule, 4
      stearylcatechol, also on Au(111), with the aim of understanding the role of the
      amide functionality in the packing, orientation, and fundamental interaction
      between the substrate and the monolayer formed from an aqueous environment by the
      Langmuir-Blodgett technique. The organization of monolayers on gold was observed
      directly and studied in detail by X-ray photoelectron spectroscopy (XPS), contact
      angle measurements (CA), surface-enhanced Raman spectroscopy (SERS), infrared
      reflection-absorption spectroscopy (IRRAS), and atomic force microscopy (AFM).
      Our study shows that within the monolayer the catecholic oxygen atoms are
      coordinated to the gold surface, having a more perpendicular orientation with
      respect to the aromatic ring and the apparently tilted alkyl chains, whereas the
      amide functionality stabilizes the monolayer that is formed.

PMID- 23157707
TI  - Mucosal advancement flap: an innovative surgical technique for treatment of lip
      vitiligo.

PMID- 23157708
TI  - Structure and reversible pyran formation in molybdenum pyranopterin dithiolene
      models of the molybdenum cofactor.
AB  - The syntheses and X-ray structures of two molybdenum pyranopterin dithiolene
      complexes in biologically relevant Mo(4+) and Mo(5+) states are reported.
      Crystallography reveals that these complexes possess a pyran ring formed through
      a spontaneous cyclization reaction of a dithiolene side-chain hydroxyl group at a
      C?N bond of the pterin. NMR data on the Mo(4+) complex suggest that a reversible
      pyran ring cyclization occurs in solution. These results provide experimental
      evidence that the pyranopterin dithiolene ligand in molybdenum and tungsten
      enzymes could participate in catalysis through dynamic processes modulated by the
      protein.

PMID- 23157709
TI  - Obesity and dental caries in children: a systematic review and meta-analysis.
AB  - OBJECTIVES: Obesity and dental caries have become increasingly prevalent
      challenges to public health. Research results into the relationship between
      obesity and dental caries in children have been mixed and inconclusive. The aim
      of this review and meta-analysis was to provide evidence to quantify the
      relationship between obesity and dental caries in children using a systematic
      approach. METHODS: A systematic search for papers between 1980 and 2010
      addressing childhood obesity and dental caries was conducted and a random effects
      model meta-analysis applied. RESULTS: Fourteen papers met the selection criteria.
      Overall, a significant relationship between childhood obesity and dental caries
      (effect size = 0.104, P = 0.049) was found. When analysed by dentition type
      (primary versus permanent), there was a nonsignificant association of obesity and
      dental caries in permanent and primary dentitions, yet on accounting only for
      standardized definitions for assessment of child obesity using body mass index, a
      strong significant relationship was evident in children with permanent
      dentitions. Moderating for study country of origin (newly 'industrialized' versus
      industrialized) showed a significant relationship between obesity and dental
      caries in children from industrialized but not newly industrialized countries.
      Cofactors such as age and socioeconomic class were significant moderators.
      CONCLUSIONS: Future analysis should investigate these confounding variables,
      helping shape the future of obesity management programmes and oral health
      interventions, through determining common risk factors.

PMID- 23157710
TI  - What is the significance of perioperative release of macrophage migration
      inhibitory factor in cardiac surgery?
AB  - Cardiac surgery is associated with release of the pleiotropic cytokine macrophage
      migration inhibitory factor (MIF). The trigger for MIF release has not yet been
      elucidated. Owing to its intrinsic antioxidative activity, MIF might reduce
      oxidative stress and protect from myocardial ischemia and reperfusion (I/R)
      injury. In the present study, patients scheduled for elective cardiac surgery
      (n=46) were randomized to undergo coronary artery bypass grafting either
      conventionally with cardiopulmonary bypass and cardioplegic arrest-induced I/R
      (cCABG) or in an off-pump procedure (OPCAB) with minimized I/R. We report that
      only patients who underwent cCABG exhibited a postoperative increase of MIF
      (p=0.024), while both groups showed an increase in interleukin-6. MIF release
      appears to be primarily mediated by I/R and to a lesser extent by inflammation.
      Endogenous peroxidase activity (p=0.021) and serum levels of thioredoxin
      (p=0.003) were significantly higher in patients who underwent cCABG after
      surgery. Interestingly, perioperative MIF release was associated with an enhanced
      antioxidant capacity and a significantly reduced postoperative incidence of
      atrial fibrillation (p=0.018) and acute kidney injury (p=0.048). The present
      study highlights the role of MIF increase during cardiac surgery in response to
      oxidative stress. Based on current observations, we hypothesize that
      intraoperative MIF secretion is due to I/R and enhances the antioxidant capacity
      in patients during cardiac surgery.

PMID- 23157712
TI  - In vivo transdermal delivery of leuprolide using microneedles and iontophoresis.
AB  - The objective of this study was to investigate the use of iontophoresis and/or
      microneedles to enhance transdermal delivery of leuprolide acetate in vivo in
      hairless rats. Microporation was achieved using 500 MUm long maltose microneedles
      and pore formation was confirmed using dye binding studies, histology studies,
      calcein imaging studies, pore permeability index calculation and trans-epidermal
      water loss measurement. Iontophoresis was performed using liquid reservoir patch
      with inbuilt silver wire electrode and a current density of 0.1 mA/cm2 was
      applied for 4 hours. Delivery studies were performed using microneedles and
      iontophoresis alone and in combination. Passive studies involving delivery
      through intact skin and injections of drug solution administered subcutaneously
      served as controls. Blood samples were collected at predetermined time points and
      plasma samples were analyzed for drug using ELISA. Significantly higher drug
      levels were detected at the end of 6 hours treatment by microneedles alone
      treatment (0.98 +/- 0.08 ng/ml) as compared to passive (0.36 +/- 0.22 ng/ml)
      delivery (p < 0.05). Further, three times more drug was found to be present
      systemically with iontophoresis alone (3.47 +/- 0.03 ng/ml) or by combination
      (3.54 +/- 0.08 ng/ml) treatments as compared to microneedles alone treatment (p <
      0.05) at the end of treatment duration. When compared to iontophoresis alone
      treatment, combination treatment resulted in faster drug delivery due to
      propulsion of the drug through the preformed micropores. In conclusion, the use
      of microneedles and/or iontophoresis seems promising for the transdermal delivery
      of peptide like leuprolide acetate.

PMID- 23157711
TI  - CNTO 530 increases expression of HbA and HbF in murine models of beta-thalassemia
      and sickle cell anemia.
AB  - CNTO 530 is an erythropoietin receptor agonist MIMETIBODYTM construct. CNTO 530
      has been shown to be active in a number of rodent models of acquired anemia (e.g.
      renal insufficiency and chemotherapy induced anemia). We investigated the
      efficacy of CNTO 530 in murine models of beta-thalassemia and sickle cell anemia
      (Berkeley mice). beta- thalassemic mice are deficient in expression of alpha
      globin chain and heterozygous mice are characterized by a clinical syndrome
      similar to the human beta-thalassemia intermedia. Berkeley mice are knocked out
      for murine alpha and beta globin and are transgenic for human alpha, beta
      (sickle) and gamma globin genes. Berkeley mice thus express human sickle
      hemoglobin A (HbS) and can also express human fetal hemoglobin. These mice
      express a severe compensated hypochromic microcytic anemia and display the sickle
      cell phenotype. To test the effectiveness of CNTO 530, mice from both genotypes
      received a single subcutaneous (s.c.) dose of CNTO 530 or darbepoetin-alpha (as a
      comparator) at 10,000 U/kg, a dose shown to cause a similar increase in
      reticulocytes and hemoglobin in normal mice. Hematologic parameters were
      evaluated over time. CNTO 530, but not darbepoetin-alpha, increased
      reticulocytes, red blood cells and total hemoglobin in beta- thalassemic mice. In
      Berkeley mice CNTO 530 showed an increase in reticulocytes, red blood cells, F
      cells, total hemoglobin and fetal hemoglobin. In conclusion, CNTO 530 is
      effective in murine models of beta-thalassemia and sickle cell anemia. These data
      suggest that CNTO 530 may have beneficial effects in patients with genetically
      mediated hemoglobinopathies.

PMID- 23157713
TI  - Quantitative comparison of cone beam computed tomography and microradiography in
      the evaluation of bone density after maxillary sinus augmentation: a preliminary
      study.
AB  - PURPOSE: Cone beam computed tomography (CBCT) and microradiographic analyses were
      comparatively performed in maxillary sinus augmentation to preliminarily verify
      the diagnostic potential of CBCT on the evaluation of bone regeneration.
      MATERIALS AND METHODS: A two-stage protocol was conducted in 19 consenting
      patients, all having the crestal bone <=2 mm, in private dental office.
      Mineralized human bone allograft particles were used to augment sinus using
      lateral window approach. A succession of CBCT scans of the maxilla was taken
      before surgery, after sinus augmentation, and immediately after implant
      insertion. Using virtual probes, CBCT data were processed by medical imaging
      software and expressed as gray level (GL). A bone core biopsy was taken at
      implant placement, 6 months after surgery. Microradiography of transverse
      sections, taken 6, 8, and 10 mm from the crestal surface, of methacrylate
      embedded biopsies was performed to analyze and to evaluate the mineralized
      material amount (MM%). RESULTS: A total of 21 sinus augmentations were performed.
      CBCT (mean GL: 646-693) data were not statistically different when comparing 6-,
      8-, and 10-mm sites to after grafting/implant-insertion values. Furthermore,
      microradiographic (mean MM%: 45.3-48.3) data were not statistically different
      comparing 6-, 8-, and 10-mm sites, due to variation of values among patients. A
      GL and MM% parallelism was identified considering each patient, instead. A
      significant correlation (p < .001) between GL and MM% was found after both
      Wilcoxon test for paired data and simple linear regression analysis. CONCLUSIONS:
      The preliminary result clearly demonstrated the predictability of the CBCT
      analysis. Due to the limited sample and great variations of the MM% recorded in
      patients, further clinical and morphometric studies are needed to fulfill
      diagnostic expectations.

PMID- 23157714
TI  - The effect of a trunk release maneuver on Peak Pressure Index, trunk displacement
      and perceived discomfort in older adults seated in a High Fowler's position: a
      randomized controlled trial.
AB  - BACKGROUND: Pressure ulcers pose significant negative individual consequences and
      financial burden on the healthcare system. Prolonged sitting in High Fowler's
      position (HF) is common clinical practice for older adults who spend extended
      periods of time in bed. While HF aids in digestion and respiration, being placed
      in a HF may increase perceived discomfort and risk of pressure ulcers due to
      increased pressure magnitude at the sacral and gluteal regions. It is likely that
      shearing forces could also contribute to risk of pressure ulcers in HF. The
      purpose of this study was to evaluate the effect of a low-tech and time-efficient
      Trunk Release Manuever (TRM) on sacral and gluteal pressure, trunk displacement
      and perceived discomfort in ambulatory older adults. METHOD: A randomized
      controlled trial was used. We recruited community-living adults who were 60 years
      of age and older using posters, newspaper advertisements and word-of-mouth.
      Participants were randomly allocated to either the intervention or control group.
      The intervention group (n = 59) received the TRM, while the control group (n =
      58) maintained the standard HF position. RESULTS: The TRM group had significantly
      lower mean (SD) PPI values post-intervention compared to the control group, 59.6
      (30.7) mmHg and 79.9 (36.5) mmHg respectively (p = 0.002). There was also a
      significant difference in trunk displacement between the TRM and control groups,
      +3.2 mm and -5.8 mm respectively (p = 0.005). There were no significant
      differences in perceived discomfort between the groups. CONCLUSION: The TRM was
      effective for reducing pressure in the sacral and gluteal regions and for
      releasing the trunk at the point of contact between the skin and the support
      surface, but did not have an effect on perceived discomfort. The TRM is a simple
      method of repositioning which may have important clinical application for the
      prevention of pressure ulcers that may occur as a result of HF.

PMID- 23157715
TI  - Hibiscus sabdariffa Linnaeus aqueous extracts attenuate the progression of renal
      injury in 5/6 nephrectomy rats.
AB  - Hibiscus sabdariffa Linn. (HS) is a tropical wild plant with antioxidant,
      antibacterial, antihypertensive, and lipid-lowering properties. In several animal
      models, HS aqueous extracts reduced the severity of the multi-organ injuries such
      as hypertension and diabetic nephropathy. One of the multiorgan injuries is
      chronic kidney disease (CKD), which results from the loss of nephron function. HS
      was used in a 5/6 nephrectomy (5/6 Nx) rat model to determine if it could
      attenuate the progression of CKD. HS (250 mg/kg/day) or placebo was orally
      administered to 5/6 Nx male Sprague-Dawley rats. The Nx+HS group had fewer renal
      injuries as measured by blood urea nitrogen, serum creatinine, creatinine
      clearance, and renal pathology when compared with the Nx group. In order to
      determine which property of HS, either vasodilatory and/or antioxidant, was
      important in attenuating the progression of CKD, systolic blood pressure (SBP)
      and serum levels of malondialdehyde (MDA) were assessed. In the Nx+HS group, the
      SBP and the serum levels of MDA were significantly lower at Week 7. In
      conclusion, through either antihypertensive and/or antioxidant properties, HS was
      able to attenuate the progression of renal injury after 5/6 Nx. Hence, HS should
      be considered as one of the new, promising drugs that can be used to attenuate
      the progression of CKD.

PMID- 23157716
TI  - EAACI taskforce position paper: evidence for autoimmune urticaria and proposal
      for defining diagnostic criteria.
AB  - An autoimmune subset of chronic spontaneous urticaria is increasingly being
      recognized internationally, based on laboratory and clinical evidence that has
      accrued over the last 20 years. This evidence has been reviewed by a taskforce of
      the Dermatology section of the European Academy of Allergy and Clinical
      Immunology. Functional autoantibodies in chronic urticaria (CU) patient sera have
      been demonstrated against IgE and FcepsilonRIalpha by basophil and mast cell
      histamine release assays and by basophil activation assays. Antibody specificity
      has been confirmed by immunoassay, but there is a poor correlation between
      functionality and immunoreactivity. Approximately 25% of CU patients have a
      positive basophil histamine release assay and show autoreactivity (a positive
      autologous serum skin test), whereas 50% are negative regarding both.
      Functionality of CU sera appears to be complement dependent on mast cells but not
      exclusively on basophils. Basophil activation by CU sera is predominantly
      restricted to IgG1 and IgG3 subclasses. Circumstantial evidence for CU being an
      autoimmune disease comes from an observed association with other autoimmune
      diseases, a strong association between serum functionality and HLA-DR4 haplotype
      and the good response of CU patients to immunotherapies. It was proposed that a
      study should be undertaken to prospectively validate potentially relevant
      clinical criteria (from the history, examination and routinely available clinical
      investigations) against a new 'gold standard' for the diagnosis of ACU (positive
      autoreactivity, functional bioassay and immunoassay) to define preliminary
      criteria sets for the diagnosis of ACU based on clinical and laboratory features
      with highest individual sensitivity and specificity.

PMID- 23157717
TI  - Relation between particle size and carotenoid bioaccessibility in carrot- and
      tomato-derived suspensions.
AB  - To study the effect of particle size on the relative all-E-beta-carotene and all
      E-lycopene bioaccessibility in carrot- and tomato-derived suspensions,
      respectively, an in vitro digestion approach including oil was used. Adding olive
      oil (2%) during digestion, especially as an oil-in-water emulsion, resulted in a
      substantial increase in carotenoid uptake in the micellar phase. Carotenoid
      bioaccessibility decreased with average particle size. Only particles smaller
      than an individual cell resulted in high bioaccessibility values, pointing out
      the importance of the cell wall as the main barrier for carotenoid uptake. The
      relation obtained between particle size and bioaccessibility was used to predict
      the carotenoid bioaccessibility in carrot- and tomato-derived purees. These
      predictions indicated that carotenoid bioaccessibility in plant-based food
      suspensions is not only determined by the cell wall integrity (related with
      particle size) but is also affected by interactions between the structural
      compounds of the complex food matrix.

PMID- 23157718
TI  - Regulation of endothelial permeability and transendothelial migration of cancer
      cells by tropomyosin-1 phosphorylation.
AB  - BACKGROUND: Loss of endothelial cell integrity and selective permeability
      barrier is an early event in the sequence of oxidant-mediated injury and may
      result in atherosclerosis, hypertension and facilitation of transendothelial
      migration of cancer cells during metastasis. We already reported that endothelial
      cell integrity is tightly regulated by the balanced co-activation of p38 and ERK
      pathways. In particular, we showed that phosphorylation of tropomyosin-1
      (tropomyosin alpha-1 chain = Tm1) at Ser283 by DAP kinase, downstream of the ERK
      pathway might be a key event required to maintain the integrity and normal
      functions of the endothelium in response to oxidative stress. METHODS:
      Endothelial permeability was assayed by monitoring the passage of Dextran-FITC
      through a tight monolayer of HUVECs grown to confluence in Boyden chambers. Actin
      and Tm1 dynamics and distribution were evaluated by immunofluorescence. We
      modulated the expression of Tm1 by siRNA and lentiviral-mediated expression of
      wild type and mutated forms of Tm1 insensitive to the siRNA. Transendothelial
      migration of HT-29 colon cancer cells was monitored in Boyden chambers similarly
      as for permeability. RESULTS: We provide evidence indicating that Tm1
      phosphorylation at Ser283 is essential to regulate endothelial permeability under
      oxidative stress by modulating actin dynamics. Moreover, the transendothelial
      migration of colon cancer cells is also regulated by the phosphorylation of Tm1
      at Ser283. CONCLUSION: Our finding strongly support the role for the
      phosphorylation of endothelial Tm1 at Ser283 to prevent endothelial barrier
      dysfunction associated with oxidative stress injury.

PMID- 23157719
TI  - Environmental impacts of the Tennessee Valley Authority Kingston coal ash spill.
      1. Source apportionment using mercury stable isotopes.
AB  - Mercury stable isotope abundances were used to trace transport of Hg-impacted
      river sediment near a coal ash spill at Harriman, Tennessee, USA. delta(202)Hg
      values for Kingston coal ash released into the Emory River in 2008 are
      significantly negative (-1.78 +/- 0.350/00), whereas sediments of the Clinch
      River, into which the Emory River flows, are contaminated by an additional Hg
      source (potentially from the Y-12 complex near Oak Ridge, Tennessee) with near
      zero values (-0.23 +/- 0.160/00). Nominally uncontaminated Emory River sediments
      (12 miles upstream from the Emory-Clinch confluence) have intermediate values (
      1.17 +/- 0.130/00) and contain lower Hg concentrations. Emory River mile 10
      sediments, possibly impacted by an old paper mill has delta(202)Hg values of 
      0.47 +/- 0.040/00. A mixing model, using delta(202)Hg values and Hg
      concentrations, yielded estimates of the relative contributions of coal ash,
      Clinch River, and Emory River sediments for a suite of 71 sediment samples taken
      over a 30 month time period from 13 locations. Emory River samples, with two
      exceptions, are unaffected by Clinch River sediment, despite occasional upstream
      flow from the Clinch River. As expected, Clinch River sediment below its
      confluence with the Emory River are affected by Kingston coal ash; however, the
      relative contribution of the coal ash varies among sampling sites.

PMID- 23157720
TI  - HCV genotype 1a shows a better virological response to antiviral therapy than HCV
      genotype 1b.
AB  - BACKGROUND: The impact of viral subtype on the rate of sustained virological
      response (SVR) to antiviral therapy in patients chronically infected with
      hepatitis C genotype 1 subtype 1a and 1b has not been extensively investigated.
      The aim of this study is to determine whether the HCV genotype 1 subtypes 1a and
      1b respond differently to treatment with PEGylated interferon (PEG-IFN) plus
      ribavirin. METHODS: For 48 weeks, 388 "naive"genotype 1 patients were treated
      weekly with PEG-IFN alpha-2a or PEG-INF alpha-2b combined with daily ribavirin
      (1000-1200 mg/day). The numbers of patients in whom HCV-RNA was undetectable were
      compared after 4 (rapid virological response, RVR), 12 (early virological
      response, EVR), and 48 (end treatment virological response, ETR) weeks of
      treatment as well as 24 weeks after the last treatment (sustained virological
      response, SVR). RESULTS: The rate of SVR was higher in subtype 1a patients than
      subtype 1b patients (55% vs. 43%; p < 0.02). Multiple logistic regression
      analysis showed that infection with genotype 1a (odds ratio(OR) : 1.8; 95%
      confidence interval (CI): 1.4 to 4.1), age < 50 years (OR:7.0; 95% CI 1.1 to
      21.2), alanine aminotransferase level (ALT)<100 IU/ml (OR:2.1; 95% CI: 1.3
      to3.5), HCV-RNA < 5.6 log10 IU/ml (OR: 3.2; 95% CI: 2.7 to 6.9) and fibrosis
      score < S3 (OR: 3.8; 95% CI:3.2 to 7.4), were all independent predictors of SVR.
      CONCLUSION: Dual antiviral therapy is more effective against HCV subtype 1a than
      against subtype 1b and this difference is independent of other factors that may
      favour viral clearance. TRIAL REGISTRATION: ClinicalTrials.gov Identifier:
      NCT01342003.

PMID- 23157721
TI  - Estimated economic benefits from low-frequency administration of atypical
      antipsychotics in treatment of schizophrenia: a decision model.
AB  - The objective of this study was to quantify the direct medical resources used
      and the corresponding burden of disease in the treatment of patients with
      schizophrenia. Because low-frequency administration (LFA) of risperidone
      guarantees adherence during treatment intervals and offers fewer opportunities to
      discontinue, adherence and persistence were assumed to improve, thereby reducing
      relapses of major symptoms.A decision tree model including Markov processes with
      monthly cycles and a five-year maximum timeframe was constructed. Costs were
      adapted from the literature and discounted at a 3% annual rate. The population is
      a demographically homogeneous cohort of patients with schizophrenia,
      differentiated by initial disease severity (mildly ill, moderately ill, and
      severely ill). Treatment parameters are estimated using published information for
      once-daily risperidone standard oral therapy (RIS-SOT) and once-monthly
      risperidone long-acting injection (RIS-LAI) with LFA therapy characteristics
      derived from observed study trends. One-year and five-year results are expressed
      as discounted direct medical costs and mean number of relapses per patient
      (inpatient, outpatient, total) and are estimated for LFA therapies given at
      three, six, and nine month intervals.The one-year results show that LFA therapy
      every 3 months (LFA-3) ($6,088) is less costly than either RIS-SOT ($10,721) or
      RIS-LAI ($9,450) with similar trends in the 5-year results. Moreover, the model
      predicts that LFA-3 vs. RIS-SOT vs. RIS LAI therapy will reduce costly inpatient
      relapses (0.16 vs. 0.51 vs. 0.41). Extending the interval to six (LFA-6) and nine
      (LFA-9) months resulted in further reductions in relapse and costs.Limitations
      include the fact that LFA therapeutic options are hypothetical and do not yet
      exist and limited applicability to compare one antipsychotic agent versus another
      as only risperidone therapy is evaluated. However, study results have quantified
      the potential health state improvements and potential direct medical cost savings
      achievable with the development and use of LFA medication delivery technologies.

PMID- 23157722
TI  - Effect of gender on the association between weight status and health-related
      quality of life in adolescents.
AB  - BACKGROUND: Some studies have investigated the association between body mass
      index (BMI) and health-related quality of life (HRQoL) among adolescents, but
      their results have been discrepant and few paid attention to the role of gender.
      The present investigation aimed to assess the relationship between weight status
      and HRQoL in adolescents and to verify whether it was similar in boys and girls.
      METHODS: Five thousand two hundred and twenty six adolescents aged 14 to 18 years
      were included in the PRomotion de l'ALIMentation et de l'Activite Physique
      (PRALIMAP) trial, a 2x2x2 factorial cluster randomized trial performed in 24 high
      schools in France. Sociodemographic, anthropometric and HRQoL data were
      collected. BMI was categorized in four classes (thin, normal-weight, overweight,
      obese). Linear regression models were used to estimate the association between
      weight status and HRQoL, adjusting for confounders. RESULTS: The mean age of
      adolescents was 15.7+/-0.6 years and their mean BMI was 21.6 +/-3.5 kg/m2; 55%
      were girls. Boys were more often overweight and obese than were girls
      (overweight: 15.6% vs 14.2%, obese: 4.8% vs 3.3%), and girls were more likely to
      be thin (5.5% vs 4.5%, p=0.0042). All HRQoL scores were higher for boys
      (p=<0.0001). Weight status was not associated with physical and social scores
      neither in boys nor in girls. Conversely, it was associated with mental score,
      but differently in girls than boys. As compared with normal-weight girls, thin
      girls had better mental HRQoL (beta=+6.17, p=0.0010), and overweight and obese
      girls had lower mental HRQoL (beta=-3.89 and beta=-5.90, respectively, p<0.001).
      Mental HRQoL was lower for thin, overweight and obese boys than for normal-weight
      boys (beta= -4.97, beta= -1.68 and beta= -3.17, respectively, p<0.0001).
      CONCLUSIONS: Gender can modify the association between weight status and HRQoL in
      adolescents. Body image could be an important target of public health programs to
      improve subjective health during adolescence.

PMID- 23157724
TI  - Laser-assisted patient positioning: a straightforward method to ensure consistent
      head and neck aesthetic photographs.

PMID- 23157723
TI  - A qualitative study of the aspirations and challenges of low-income mothers in
      feeding their preschool-aged children.
AB  - BACKGROUND: The prevalence of obesity among preschool-aged children has
      increased, especially among those in low-income households. Two promising
      behavioral targets for preventing obesity include limiting children's portion
      sizes and their intake of foods high in solid fats and/or added sugars, but these
      approaches have not been studied in low-income preschoolers in the home setting.
      The purpose of this study was to understand the contextual factors that might
      influence how low-income mothers felt about addressing these behavioral targets
      and mothers' aspirations in feeding their children. METHODS: We recruited 32
      English-speaking women in Philadelphia, Pennsylvania who were eligible for the
      Supplemental Nutrition Assistance Program and who were the biologic mothers of
      children 36 to 66 months of age. Each mother participated in 1 of 7 focus groups
      and completed a brief socio-demographic questionnaire. Focus group questions
      centered on eating occasions, foods and drinks consumed in the home, and portion
      sizes. Each focus group lasted 90 minutes and was digitally recorded and
      transcribed verbatim. Three authors independently identified key themes and
      supporting quotations. Themes were condensed and modified through discussion
      among all authors. RESULTS: Thirty-one mothers identified themselves as black, 15
      had a high school education or less, and 22 lived with another adult. Six themes
      emerged, with three about aspirations mothers held in feeding their children and
      three about challenges to achieving these aspirations. Mothers' aspirations were
      to: 1) prevent hyperactivity and tooth decay by limiting children's sugar intake,
      2) use feeding to teach their children life lessons about limit setting and
      structure, and 3) be responsive to children during mealtimes to guide decisions
      about portions. Especially around setting limits with sweets and snacks, mothers
      faced the challenges of: 1) being nagged by children's food requests, 2) being
      undermined by other adults in the family, and 3) having bad memories from
      childhood that made it hard to deny children's food requests. CONCLUSIONS:
      Although the primary aspirations of low-income mothers in feeding their preschool
      aged children were not focused on children's weight, these aspirations were
      compatible with obesity prevention strategies to limit children's portion sizes
      and their intake of solid fats and/or added sugars.

PMID- 23157725
TI  - Anharmonicity of weakly bound Li(+)-(H2)n (n = 1-3) complexes.
AB  - The anharmonicity of Li(+)-(H(2))(n) (n = 1, 2, and 3) complexes is studied using
      the vibrational self-consistent field (VSCF) approach. The H-H stretching
      frequency shifts of Li(+)-(H(2))(n) complexes are calculated with the coupled
      cluster method including all single and double excitations with perturbative
      triples (CCSD(T)) level of theory with the cc-pVTZ basis set. The calculated IR
      active H-H stretching frequency in Li(+)-H(2), Li(+)-(H(2))(2) and Li(+)
      (H(2))(3) is red-shifted by 121, 109, and 96-99 cm(-1), respectively, relative to
      that of isolated H(2). The calculated red shifts and their trends are in good
      agreement with the available experimental data.

PMID- 23157726
TI  - Pharmacology of dimethanesulfonate alkylating agents: busulfan and treosulfan.
AB  - INTRODUCTION: Among the dimethanesulfonates, busulfan, in combination with other
      alkylating agents or nucleoside analogues, is the cornerstone of high-dose
      chemotherapy. It is used, and followed hematopoietic stem cell transplantation,
      for the treatment of various hematologic malignancies and immunodeficiencies.
      Treosulfan, which is a hydrophilic analogue of busulfan, was the first
      dimethanesufonate registered for the treatment of ovarian cancer. Recently,
      treosulfan has been investigated for the treatment of hematologic malignancies in
      combination with the same second agents before hematopoietic stem cell
      transplantation. AREAS COVERED: This work reviews the pharmacological data of
      these two dimethanesulfonates alkylating agents. Specifically, the article looks
      at their chemistry, metabolism, anticancer activity, and their pharmacokinetics
      and pharmacodynamics. EXPERT OPINION: Busulfan has been investigated widely for
      more than three decades leading to a large and precise handling of this agent
      with numerous studies on activity and pharmacokinetics and pharmacodynamics. In
      contrast, the behavior of treosulfan is still under investigation and not fully
      described. The complexity of treosulfan's metabolism and mechanism of action
      gives rise to the need of a deeper understanding of its pharmacological activity
      in a context of high-dose chemotherapy. Specifically, there is a great need to
      better understand its pharmacokinetics/pharmacodynamics relationship.

PMID- 23157727
TI  - Wormlike micelle formation by acylglutamic acid with alkylamines.
AB  - Rheological properties of alkyl dicarboxylic acid-alkylamine complex systems have
      been characterized. The complex materials employed in this study consist of an
      amino acid-based surfactant (dodecanoylglutamic acid, C12Glu) and a tertiary
      alkylamine (dodecyldimethylamine, C12DMA) or a secondary alkylamine
      (dodecylmethylamine, C12MA). (1)H NMR and mass spectroscopic data have suggested
      that C12Glu forms a stoichiometric 1:1 complex with C12DMA and C12MA. Rheological
      measurements have suggested that the complex systems yield viscoelastic wormlike
      micellar solutions and the rheological behavior is strongly dependent on the
      aqueous solution pH. This pH-dependent behavior results from the structural
      transformation of the wormlike micelles to occur in the narrow pH range 5.5-6.2
      (in the case of C12Glu-C12DMA system); i.e., positive curved aggregates such as
      spherical or rodlike micelles tend to be formed at high pH values. Our current
      study offers a unique way to obtain viscoelastic wormlike micellar solutions by
      means of alkyl dicarboxylic acid-alkylamine complex as gemini-like amphiphiles.

PMID- 23157729
TI  - Differences in the cost of admitted patient care for Indigenous people and people
      from remote locations.
AB  - The introduction of activity-based funding (ABF) means that Australian Refined
      Diagnosis Related Groups and their relative costs will become the basis for
      reimbursing public hospitals for admitted patient services. This study sought to
      investigate the variation in admitted patient costs for Indigenous people and
      people from remote areas that cannot be explained by variation in the clinical
      mix of cases, and to interpret this variation within an ABF framework. The study
      used a dataset of discharges from public hospitals of Northern Territory
      residents between July 2007 and June 2009. Multivariate regression analysis was
      used to estimate the variation in average costs, using the logarithm of patient
      cost as the dependent variable and Major Diagnostic Categories (MDCs), hospitals
      and population subgroups (Indigenous v. non-Indigenous; urban v. remote) as
      independent variables. Although much of the additional cost of Indigenous and
      remote patients was found to be due to differences in severity and complexity
      between MDCs, there were extra costs for remote Indigenous patients that were not
      captured by the classification system. Hospitals servicing larger than average
      proportions of these patients could be systematically underfunded within an ABF
      framework unless a price adjustment is applied.

PMID- 23157728
TI  - Radical-translocation intermediates and hurdling of pathway defects in "super
      oxidized" (Mn(IV)/Fe(IV)) Chlamydia trachomatis ribonucleotide reductase.
AB  - A class I ribonucleotide reductase (RNR) uses either a tyrosyl radical (Y(*)) or
      a Mn(IV)/Fe(III) cluster in its beta subunit to oxidize a cysteine residue ~35 A
      away in its alpha subunit, generating a thiyl radical that abstracts hydrogen
      (H(*)) from the substrate. With either oxidant, the inter-subunit "hole-transfer"
      or "radical-translocation" (RT) process is thought to occur by a "hopping"
      mechanism involving multiple tyrosyl (and perhaps one tryptophanyl) radical
      intermediates along a specific pathway. The hopping intermediates have never been
      directly detected in a Mn/Fe-dependent (class Ic) RNR nor in any wild-type (wt)
      RNR. The Mn(IV)/Fe(III) cofactor of Chlamydia trachomatis RNR assembles via a
      Mn(IV)/Fe(IV) intermediate. Here we show that this cofactor-assembly intermediate
      can propagate a hole into the RT pathway when alpha is present, accumulating
      radicals with EPR spectra characteristic of Y(*)'s. The dependence of Y(*)
      accumulation on the presence of substrate suggests that RT within this "super
      oxidized" enzyme form is gated by the protein, and the failure of a beta variant
      having the subunit-interfacial pathway Y substituted by phenylalanine to support
      radical accumulation implies that the Y(*)(s) in the wt enzyme reside(s) within
      the RT pathway. Remarkably, two variant beta proteins having pathway
      substitutions rendering them inactive in their Mn(IV)/Fe(III) states can generate
      the pathway Y(*)'s in their Mn(IV)/Fe(IV) states and also effect nucleotide
      reduction. Thus, the use of the more oxidized cofactor permits the accumulation
      of hopping intermediates and the "hurdling" of engineered defects in the RT
      pathway.

PMID- 23157731
TI  - Working memory compensates for hearing related phonological processing deficit.
AB  - Acquired hearing impairment is associated with gradually declining phonological
      representations. According to the Ease of Language Understanding (ELU) model,
      poorly defined representations lead to mismatch in phonologically challenging
      tasks. To resolve the mismatch, reliance on working memory capacity (WMC)
      increases. This study investigated whether WMC modulated performance in a
      phonological task in individuals with hearing impairment. A visual rhyme judgment
      task with congruous or incongruous orthography, followed by an incidental
      episodic recognition memory task, was used. In participants with hearing
      impairment, WMC modulated both rhyme judgment performance and recognition memory
      in the orthographically similar non-rhyming condition; those with high WMC
      performed exceptionally well in the judgment task, but later recognized few of
      the words. For participants with hearing impairment and low WMC the pattern was
      reversed; they performed poorly in the judgment task but later recognized a
      surprisingly large proportion of the words. Results indicate that good WMC can
      compensate for the negative impact of auditory deprivation on phonological
      processing abilities by allowing for efficient use of phonological processing
      skills. They also suggest that individuals with hearing impairment and low WMC
      may use a non-phonological approach to written words, which can have the
      beneficial side effect of improving memory encoding. LEARNING OUTCOMES: Readers
      will be able to: (1) describe cognitive processes involved in rhyme judgment, (2)
      explain how acquired hearing impairment affects phonological processing and (3)
      discuss how reading strategies at encoding impact memory performance.

PMID- 23157732
TI  - Specialist trainees on rotation cannot replace dedicated consultant clinicians
      for antimicrobial stewardship of specialty disciplines.
AB  - Our prospective-audit-and-feedback antimicrobial stewardship (AS) program for
      hematology and oncology inpatients was switched from one led by dedicated
      clinicians to a rotating team of infectious diseases trainees in order to provide
      learning opportunities and attempt a "de-escalation" of specialist input towards
      a more protocol-driven implementation. However, process indicators including the
      number of recommendations and recommendation acceptance rates fell significantly
      during the year, with accompanying increases in broad-spectrum antibiotic
      prescription. The trends were reversed only upon reverting to the original setup.
      Dedicated clinicians play a crucial role in AS programs involving
      immunocompromised patients. Structured training and adequate
      succession/contingency planning is critical for sustainability.

PMID- 23157730
TI  - Acute cognitive and behavioral effects of systemic corticosteroids in children
      treated for inflammatory bowel disease.
AB  - Systemic corticosteroids are a mainstay of treatment for many pediatric medical
      conditions. Although their impact on the central nervous system has been well
      studied in animal models and adults, less is known about such effects in
      pediatric populations. The current study investigated acute effects of
      corticosteroids on memory, executive functions, emotion, and behavior in children
      and adolescents with inflammatory bowel disease (IBD). Patients 8-17 years with
      IBD (Crohn's disease, CD; ulcerative colitis, UC) on high-dose prednisone (n =
      33) and IBD patients in remission off steroids (n = 33) completed standardized
      neuropsychological tests and behavior rating scales. In the IBD sample as a
      whole, few steroid effects were found for laboratory cognitive measures, but
      steroid-treated patients were rated as exhibiting more problems with emotional,
      and to a lesser extent with cognitive function in daily life. Steroid effects,
      assessed by laboratory measures and questionnaires, were more prevalent in CD
      than UC patients; UC patients on steroids sometimes performed better than
      controls. Sleep disruption also predicted some outcomes, diminishing somewhat the
      magnitude of the steroid effects. Corticosteroid therapy can have acute effects
      on cognition, emotion, and behavior in chronically ill children; the clinical and
      long-term significance of these effects require further investigation.

PMID- 23157733
TI  - Quality of reporting of clinical non-inferiority and equivalence randomised
      trials--update and extension.
AB  - BACKGROUND: Non-inferiority and equivalence trials require tailored methodology
      and therefore adequate conduct and reporting is an ambitious task. The aim of our
      review was to assess whether the criteria recommended by the CONSORT extension
      were followed. METHODS: We searched the Medline database and the Cochrane Central
      Register for reports of randomised non-inferiority and equivalence trials
      published in English language. We excluded reports on bioequivalence studies,
      reports targeting on other than the main results of a trial, and articles of
      which the full-text version was not available. In total, we identified 209
      reports (167 non-inferiority, 42 equivalence trials) and assessed the reporting
      and methodological quality using abstracted items of the CONSORT extension.
      RESULTS: Half of the articles did not report on the method of randomisation and
      only a third of the trials were reported to use blinding. The non-inferiority or
      equivalence margin was defined in most reports (94%), but was justified only for
      a quarter of the trials. Sample size calculation was reported for a proportion of
      90%, but the margin was taken into account in only 78% of the trials reported.
      Both intention-to-treat and per-protocol analysis were presented in less than
      half of the reports. When reporting the results, a confidence interval was given
      for 85% trials. A proportion of 21% of the reports presented a conclusion that
      was wrong or incomprehensible. Overall, we found a substantial lack of quality in
      reporting and conduct. The need to improve also applied to aspects generally
      recommended for randomised trials. The quality was partly better in high-impact
      journals as compared to others. CONCLUSIONS: There are still important
      deficiencies in the reporting on the methodological approach as well as on
      results and interpretation even in high-impact journals. It seems to take more
      than guidelines to improve conduct and reporting of non-inferiority and
      equivalence trials.

PMID- 23157734
TI  - Analytical molecular and biomolecular spectroscopy: basics and applications.

PMID- 23157735
TI  - Impact of adequate empirical combination therapy on mortality from bacteremic
      Pseudomonas aeruginosa pneumonia.
AB  - BACKGROUND: Pseudomonas aeruginosa has gained an increasing amount of attention
      in the treatment of patients with pneumonia. However, the benefit of empirical
      combination therapy for pneumonia remains unclear. We evaluated the effects of
      adequate empirical combination therapy and multidrug-resistance in bacteremic
      Pseudomonas pneumonia on the mortality. METHODS: A retrospective cohort study was
      performed at the 2,700-bed tertiary care university hospital. We reviewed the
      medical records of patients with bacteremic pneumonia between January 1997 and
      February 2011. Patients who received either inappropriate or appropriate
      empirical therapy were compared by using marginal structural model. Furthermore,
      we investigated the direct impact of combination therapy on clinical outcomes in
      patients with monomicrobial bacteremic pneumonia. RESULTS: Among 100 consecutive
      patients with bacteremic Pseudomonas pneumonia, 65 patients were classified in
      the adequate empirical therapy group, 32 of whom received monotherapy and 33
      combination therapy. In the marginal structural model, only inadequate therapy
      was significantly associated with 28-day mortality (p = 0.02), and multidrug
      resistance was not a significant risk factor.To examine further the direct impact
      of combination therapy, we performed a subgroup analysis of the 65 patients who
      received adequate therapy. Multivariate logistic regression analysis identified
      absence of septic shock at the time of bacteremia (OR, 0.07; 95% CI, 0.01-0.49; p
      = 0.008), and adequate combination therapy (OR, 0.05; 95% CI, 0.01-0.34; p =
      0.002) as variables independently associated with decreased all-cause 28-day
      mortality. CONCLUSIONS: Our study suggests that adequate empirical combination
      therapy can decrease mortality in patients with bacteremic Pseudomonas pneumonia.

PMID- 23157736
TI  - Detection and differentiation of genotype I and III Japanese encephalitis virus
      in mosquitoes by multiplex reverse transcriptase-polymerase chain reaction.
AB  - Japanese encephalitis (JE) is a disease that threatens both human and animal
      populations in Asian countries, and the causative agent of JE, Japanese
      encephalitis virus (JEV), has recently changed from genotype III (GIII) to
      genotype I (GI). However, a test for the rapid differentiation of GI and GIII JEV
      is still unavailable, especially one that can be used for mosquito-based
      surveillance. We have designed GI- and GIII-specific primer sets for the rapid
      detection and differentiation of GI and GIII JEV by multiplex reverse
      transcriptase-polymerase chain reaction (multiplex RT-PCR). The GI-specific and
      GIII-specific primer sets were able to specifically amplify the target gene from
      GI and GIII JEV, respectively. The limitations of detection were 0.00225 and
      0.225 pfu for the GI-specific and GIII-specific primers, respectively. Using a
      mixture of GI-specific and GIII-specific primers, the multiplex RT-PCR was able
      to specifically detect and differentiate GI and GIII JEV. The multiplex RT-PCR
      was able to successfully differentiate GI and GIII virus in JEV-infected
      mosquitoes. Thus, a sensitive and specific multiplex RT-PCR system for the rapid
      detection and differentiation of GI and GIII JEV has been developed, and this
      test is likely to be valuable when carrying out mosquito-based JEV surveillance. 

PMID- 23157737
TI  - Coagulation imbalance may not contribute to the development of portal vein
      thrombosis in patients with cirrhosis.
AB  - INTRODUCTION: The relationship between the imbalance in pro- and anti-coagulant
      factors and portal vein thrombosis (PVT) in individuals with cirrhosis is
      unclear. The aim of this study was to determine whether the imbalance in pro- and
      anti-coagulant factors contributes to the development of PVT in cirrhotic
      patients. MATERIALS AND METHODS: Blood samples were collected from 30 consecutive
      cirrhotic patients with PVT and 30 age-, sex-, and Child-Pugh score-matched
      cirrhotic patients without PVT (controls), and the plasma levels of coagulation
      factors II, V, VII, VIII, IX, X, XI and XII and of protein C (PC), protein S (PS)
      and antithrombin (AT) were analyzed. The ratios of pro- vs. anti-coagulant
      factors were further investigated. RESULTS: The levels of pro- and anti-coagulant
      factors were not statistically different between the PVT and control groups.
      Similar results were obtained when the patients were divided according to Child
      Pugh classification. No difference was observed for the ratios of pro- vs. anti
      coagulant factors between the two groups but the ratios of factor II-to-PC and
      factor VII-to-PC which were significantly decreased in the PVT group. Most of the
      ratios did not reach statistical significance in each Child-Pugh category except
      the followings: factor VIII-to-PS, factor XII-to-PC and factor XII-to-PS in class
      A patients; factor II-to-PS, factor VII-to-PC and factor VII-to-PS in class B
      patients. But the difference might not be so convincing. CONCLUSIONS: PVT in
      cirrhotic patients may not result from coagulation imbalance.

PMID- 23157738
TI  - Transesophageal echocardiography in the diagnosis of acute pericardial tamponade
      during hiatal hernia repair.

PMID- 23157739
TI  - Triterpenoid content of berries and leaves of bilberry Vaccinium myrtillus from
      Finland and Poland.
AB  - Triterpenoid compounds found in free and ester forms in extracts of entire fruits
      and leaves and in fruit and leaf cuticular waxes of bilberry (Vaccinium myrtillus
      L.) collected in Finland and Poland were identified and quantitated by gas
      chromatography-mass spectrometry coupled to a flame ionization detector (GC
      MS/FID). The main bilberry triterpenoid profile consisted of alpha- and beta
      amyrin, alpha- and beta-amyrenone, campesterol, cholesterol, citrostadienol (in
      berries), cycloartanol, erythrodiol, lupeol, 24-methylenecycloartanol,
      sitosterol, sitostanol, stigmasterol, stigmasta-3,5-dien-7-one, uvaol, oleanolic
      and ursolic aldehydes, and oleanolic, ursolic, 2alpha-hydroxyoleanolic, and
      2alpha-hydroxyursolic acids. Friedelin and D:A-friedooleanan-3beta-ol were found
      only in Finnish plants, whereas D:C-friedours-7-en-3beta-ol and taraxasterol were
      found only in Polish plants. To our knowledge, this is the first thorough
      description of triterpenoid compounds in this species. The presented results
      revealed that the triterpenoid profile of bilberry varied considerably between
      different organs of the plant, regardless of the plant origin, as well as between
      plant samples obtained from the two geographical locations.

PMID- 23157740
TI  - [Relevance of molecular alterations in histopathologic subtyping of lung
      adenocarcinoma based on 2011 International Multidisciplinary Lung Adenocarcinoma
      Classification].
AB  - OBJECTIVE: To evaluate the relevance of molecular alterations and
      histopathological subtypes of lung adenocarcinoma according to 2011 International
      Association for the Study of Lung Cancer/American Thoracic Society/European
      Respiratory Society International Multidisciplinary Lung Adenocarcinoma
      Classification. METHODS: Mutations of epidermal growth factor receptor (EGFR) 18
      21 exons (E18-21), KRAS 12/13 codons and EML4-ALK fusion in 212 cases of lung
      adenocarcinoma which underwent complete tumor resection, were detected by
      immunohistochemistry, PCR-amplifying and gene sequencing. The relevance of the
      molecular alterations to histopathological subtypes based on the new
      classification and 2004 WHO classification were further characterized. RESULTS:
      Mutations of EGFR were observed in 49.6% of lung adenocarcinomas, involving
      mainly E21 (52.4%, 55/105) and E19 (36.2%, 38/105). Mutations of KRAS were
      detected in 8% cases of adenocarcinoma, involving mainly codon 12 (15/17). EML4
      ALK fusions were found in 6.1% of lung adenocarcinoma, the most common fusion
      mutation was type V1 (E13; A20) (7/13), followed by type V3a/b (E6a/b; A20)
      (4/13). Based on the new classification, 7/10 lepidic, 63.2% (48/76) papillary,
      and 5/8 micropapillary predominant adenocarcinomas harbored EGFR mutations. EGFR
      mutations showed significant difference among different histological subtypes (P
      = 0.008). KRAS mutations were most frequently found in invasive mucinous
      adenocarcinoma (1/2), followed by colloid predominant adenocarcinoma (3/7). There
      was significant difference of KRAS mutations among different histological
      subtypes (P = 0.003). EML4-ALK fusions were most frequently found in the solid
      predominant with mucin production subtype (15.4%, 6/39), followed by colloid
      predominant adenocarcinoma (1/7), and no significant difference of EML4-ALK
      fusions was found among different histological subtypes (P = 0.181). Significant
      TTF-1 overexpression was observed in adenocarcinomas harbored EGFR mutations (P =
      0.008), and no or significantly lower level expression of TTF-1 was observed in
      adenocarcinomas harbored KRAS mutations (P = 0.000). However, there was no
      association between TTF-1 expression and EML4-ALK fusions (P = 0.274). Based on
      the 2004 WHO classification, mutations of KRAS (P = 0.002) and EML4-ALK (P =
      0.000), rather than EGFR (P = 0.502), showed significant differences among
      different subtypes. According to both classification systems, the difference of
      "triple negative" adenocarcinomas was not significant among different subtypes (P
      = 0.684, P = 0.449, respectively). CONCLUSIONS: The new classification, combined
      with TTF-1 immunomarker, can help to predict the molecular alterations of EGFR
      and KRAS genes, but can not indicate the EML4-ALK fusion in lung adenocarcinoma.
      Lepidic, papillary, and micropapillary predominant adenocarcinomas with TTF-1
      expression are closely related to the presence of EGFR mutation, and invasive
      mucinous adenocarcinoma, while colloid predominant adenocarcinoma without TTF-1
      expression is closely related to the presence of KRAS mutation.

PMID- 23157741
TI  - [Interleukin 7 and its receptor promote cell proliferation and induce
      lymphangiogenesis in non-small cell lung cancer].
AB  - OBJECTIVE: To study the mechanism of interleukin 7/interleukin 7 receptor (IL
      7/IL-7R) in promoting cell proliferation and inducing lymphangiogenesis of non
      small cell lung cancer (NSCLC) in vivo and in vitro. METHODS: Immunohistochemical
      study for IL-7, IL-7R, cyclin D1 and vascular endothelial growth factor-D (VEGF
      D) was carried out in NSCLC tissues from 95 patients. The relationship between IL
      7/IL-7R expression and various parameters was analyzed. The mechanism of IL-7/IL
      7R in promoting cell proliferation and inducing lymphangiogenesis was studied by
      methylthiazolyldiphenyl-tetrazolium bromide, fluorescence-activated cell sorting,
      reverse transcriptase-PCR, Western blot, co-immunoprecipitation, chromatin
      immunoprecipitation and nude mice experiments with xenograft tumors. RESULTS: IL
      7 (63.2%, 60/95), IL-7R (61.1%, 58/95), cyclin D1 (52.6%, 50/95) and VEGF-D
      (58.9%, 56/95) showed that high level of expression in NSCLC. IL-7/IL-7R over
      expression correlated with cyclin D1 expression (P < 0.01, P < 0.01), VEGF-D
      expression (P < 0.01, P < 0.01), increased lymphovascular density (P = 0.005, P =
      0.013), advanced clinical stage (P = 0.008, P = 0.005) and presence of lymph node
      metastasis (P < 0.01, P < 0.01). IL-7/IL-7R could promote proliferation of A549
      cell, increase cyclin D1 and VEGF-D expression, and enhance c-Fos/c-Jun
      expression and phosphorylation, resulting in formation of heterodimer.
      Furthermore, IL-7/IL-7R could induce binding of c-Fos/c-Jun to cyclin D1/VEGF-D
      promoters and regulate their transcription. IL-7/IL-7R could also promote
      proliferation and lymphangiogenesis of lung cancer xenograft tumors. CONCLUSIONS:
      IL-7/IL-7R promotes c-Fos/c-Jun expression and activity in NSCLC. This further
      facilitates cyclin D1 expression and accelerates proliferation of cells and VEGF
      D-induced lymphovascular formation.

PMID- 23157742
TI  - [Utility of NUT gene expression and rearrangement in diagnosis of NUT midline
      carcinoma in upper respiratory tract].
AB  - OBJECTIVE: To investigate the importance of expression of the NUT gene and its
      rearrangement in diagnosing NUT midline carcinoma (NMC) of the upper respiratory
      tract; and to evaluate the prevalence, histological features and differential
      diagnosis of NMC of the upper respiratory tract. METHODS: One-hundred and sixty
      three small cell malignant tumors of the upper respiratory tract were reviewed at
      the Beijing Tongren Hospital, Capital Medical University over a 20-year period.
      These cases included poorly-differentiated squamous cell carcinomas (n = 31),
      undifferentiated carcinoma (n = 1), non-keratizing undifferentiated nasopharyneal
      carcinomas (n = 60), small cell neuroendocrine carcinomas (n = 6) and non
      epithelial small round cell malignant tumors (n = 65). The clinical and
      pathologic features were investigated. All cases were subjected to Epstein-Barr
      virus encoded RNA (EBER) in situ hybridization and NUT monoclonal antibody
      immunohistochemical staining. Cases positive for NUT immunohistochemistry and
      negative for EBER in situ hybridization were submitted for fluorescent in situ
      hybridization (FISH) for rearrangements in both BRD4 and NUT genes, and
      immunohistochemical staining for a set of cytokeratins (AE1/AE3, CK7, CK8),
      p63,and neuroendocrine markers (NSE, Syn, CgA, S-100 protein, CD56). RESULTS:
      Three cases of poorly-differentiated squamous cell carcinomas and one case of
      undifferentiated carcinoma showed diffuse nuclear immunohistochemical staining
      with antibody against NUT. These positive cases approximately accounted for 12.5%
      (4/32) of this group, 4.1% (4/98) of the malignant epithelial carcinomas and 2.5%
      (4/163) of all small round cell malignant tumors in the study. The age of these
      patients were 42 - 59 years. Other groups were all negative for NUT
      immunohistochemistry. These four cases also stained for antibodies against
      cytokeratins and p63, but were negative for neuroendocrine markers and not
      associated with EBV infection. Only two of these four cases showed rearrangements
      of the NUT and BRD4 genes by FISH. These two patients died within one year. The
      other two patients that did not demonstrate NUT rearrangement by FISH were alive
      and did not have an aggressive clinical course, surviving 40 and 12 months
      respectively. CONCLUSIONS: NMC is a rare small round cell malignant tumor in the
      upper respiratory tract. Only in the groups of primary poorly differentiated
      squamous cell carcinoma and undifferentiated carcinoma were positive for NUT
      immunohistochemical staining and NUT rearrangement by FISH. NMC typically occurs
      in midline organs, and affects the sinonasal tract. It is not associated with EBV
      infection. There is difference in the clinical course and prognosis among NMC
      patients. NUT immunohistochemical staining and NUT gene rearrangement analysis
      can differentiate NMC from other small cell tumors in the upper respiratory
      tract.

PMID- 23157743
TI  - [Pulmonary neuroendocrine cell hyperplasia and tumorlets in bronchiectasis: a
      clinicopathologic study of 22 cases with review of literature].
AB  - OBJECTIVE: To study the clinical and pathological features of pulmonary
      neuroendocrine cell hyperplasia and tumorlets with bronchiectasis. METHODS: Both
      the clinicopathologic changes and immunohistochemical findings were examined with
      microscopy and EnVision method in 22 cases of pulmonary neuroendocrine cell
      hyperplasia and tumorlets. RESULTS: The average age of the 22 patients was 53
      years, with a male to female ratio of 9:13. On macroscopic examination the lungs
      showed bronchiectasis; one case was accompanied by gray-white, soft nodules
      (diameter < 5 mm). Microscopy of the HE sections showed the basic pathologic
      change was bronchiectasis, accompanied by neuroendocrine cell hyperplasia and
      tumorlet formation in the pulmonary parenchyma surrounding the bronchioles,
      presenting as single nodule (10 patients), or multifocal nodules (12 patients),
      with average size of 1.6 mm in diameter. No tumor cells were identified in the
      lymph nodes. Sixteen of 22 patients were disease-free after an average follow-up
      period of 58 months (17 - 117 months); one patient died suddenly after surgery;
      and five were loss of follow up. Immunohistologically, the tumor cells were
      positive for CgA (18/18), Syn (16/16), AE1/AE3 (16/16) , TTF-1 (14/15), and CD56
      (14/14), and Ki-67 index was < 2% in 12 cases. CONCLUSIONS: Immunohistological
      staining for CgA, Syn, CD56, TTF-1 and AE1/AE3 can confirm the diagnosis. Early
      detection, pulmonary resection and follow-up help prevent the progression of
      these diseases.

PMID- 23157744
TI  - [Detection of epidermal growth factor receptor gene mutations in advanced non
      small cell lung cancer].
AB  - OBJECTIVE: To investigate the mutations of epidermal growth factor receptor
      (EGFR) in tumor tissue and pleural effusion in advanced non-small cell lung
      cancer (NSCLC) patients, and to analyze the relationship between EGFR mutations
      and the clinicopathologic characteristics. METHODS: Two-hundred and forty-one
      cases of formalin-fixed, paraffin-embedded tumor tissues and 14 paired pleural
      effusions from advanced NSCLC patients were collected. Twenty-nine different EGFR
      mutations in exons 18-21 were assessed by scorpions and amplification refractory
      mutation system (scorpions ARMS) using real time PCR. The relationship between
      the EGFR mutations and clinical parameters was analyzed using statistical
      methods. EGFR mutation of 37 cases were detected with direct sequencing, and
      assessed the sensitivity, the specificity and the accuracy of scorpions ARMS.
      RESULTS: EGFR somatic mutations were detected in 114 of 234 advanced NSCLC
      patients, with the mutation rate of 48.7%, including deletions in exon 19 in 65
      patients and point mutation of L858R in exon 21 in 39 patients; both accounting
      for 91.2% (104/114) of all types of EGFR mutations. The test results of 14 paired
      pleural effusion specimens were entirely the same to the tissues. The concordance
      rate of 2 different detection methods was 94.6%. Mutation rate was higher in
      women (55.9%) than in men (42.2%), and there was no difference in mutation rates
      between smokers and non-smokers; patients in stage IIIB and stage IV;
      adenocarcinoma and non-adenocarcinoma. CONCLUSIONS: EGFR somatic mutations appear
      to occur frequently in Chinese. Scorpions ARMS technology is a sensitive method
      to detect EGFR mutations and is suitable for screening patients who would likely
      respond to EGFR inhibitors therapy.

PMID- 23157745
TI  - [Clinicopathologic analysis of dysembryoplastic neuroepithelial tumor].
AB  - OBJECTIVE: To study the clinicopathologic features, radiologic findings,
      treatment options and prognosis of dysembryoplastic neuroepithelial tumor (DNT).
      METHODS: The clinicopathologic and radiologic features were retrospectively
      analyzed in 10 cases of DNT. RESULTS: Intractable partial seizure was the main
      presenting symptom in all patients. The tumor was located in temporal lobe
      (number = 5), frontal lobe (number = 3) or parietal lobe (number = 2). CT scan
      displayed a hypodense lesion. MRI scan revealed the tumor was non-enhancing T1WI
      hypointense and T2WI hyperintense, with internal septation and hyperintense ring
      around the tumor seen on FLAIR image. There was neither peritumoral edema nor
      mass effect. Histologically, the tumor showed the presence of glioneuronal
      element, with oligodendrocyte-like cells, floating neurons, astrocytes and
      associated microcystic changes. Immunohistochemical study demonstrated positivity
      for NeuN and synaptophysin in the neurons and some oligodendrocyte-like cells.
      Olig2 and S-100 protein were also expressed in the oligodendrocyte-like cells. Ki
      67 index were lower than 1% in all cases. Nine cases were treated by complete
      surgical excision and the remaining case was subtotally excised. No post
      operative chemotherapy or radiotherapy was given. One of the 10 cases recurred on
      follow up. CONCLUSIONS: Correct diagnosis of DNT requires correlation with
      clinicopathologic, radiologic and immunohistochemical findings. Complete
      resection of the tumor and epileptogenic foci is the mainstay of treatment for
      DNT, with intraoperative EEG monitoring. Post-operative chemotherapy or
      radiotherapy is not required.

PMID- 23157746
TI  - [Pathologic diagnosis and differential diagnosis of small cell neuroendocrine
      carcinoma of kidney].
AB  - OBJECTIVE: To study the clinicopathologic features and histologic differential
      diagnosis of small cell neuroendocrine carcinoma (SmCC) of kidney. METHODS: The
      clinicopathologic features of 12 cases of SmCC of kidney encountered during the
      period from 1999 to 2010 were retrospectively reviewed. RESULTS: Six cases of
      primary and 6 cases of metastatic SmCC involving kidney were identified. Amongst
      the primary renal SmCC, 2 were located in renal parenchyma and 4 in renal pelvis.
      Chest X-ray showed negative findings. Five of them underwent radical nephrectomy.
      On gross examination, the tumor was located centrally around the renal pelvis in
      4 cases and peripherally in renal parenchyma in 1 case. On the other hand, 4 of
      the 6 cases of metastatic SmCC were discovered during therapy for pulmonary SmCC.
      Two of these patients presented with abdominal pain and gross hematuria, with
      lung and renal tumor masses identified simultaneously. The diagnosis of all the 6
      cases of metastatic SmCC was confirmed by fine needle aspiration biopsy.
      Microscopically, pure SmCC was demonstrated in the 2 cases of primary renal
      parenchymal SmCC and 6 cases of metastatic SmCC. The 4 primary renal pelvic SmCC
      coexisted with urothelial carcinoma component. On immunohistochemical study, all
      cases were positive for cytokeratin, synaptophysin and CD56. All metastatic cases
      and 4 primary cases were also positive for TTF-1. Of six patients with primary
      SmCC two died 4 and 9 months after operation, and two were alive with a follow-up
      of 25 and 138 months, respectively. Five of six cases with metastatic SmCC died 3
      - 8 months after diagnosis. The other 3 cases were failed to follow-up.
      CONCLUSIONS: Both primary and metastatic SmCC can be found in the kidney.
      Although rare, primary SmCC is located either in renal parenchyma or in pelvis.
      The diagnosis of SmCC relies on morphologic examination and immunohistochemical
      study. TTF-1 immunostaining cannot reliably distinguish primary from metastatic
      SmCC in kidney. Correlation with clinicoradiologic findings and demonstration of
      coexisting urothelial carcinoma component (if any) is helpful in delineation of
      the tumor origin.

PMID- 23157747
TI  - [Clinical and pathologic features of tubulocystic carcinoma of kidney].
AB  - OBJECTIVE: To investigate clinicopathological features and differential diagnosis
      of tubulocystic carcinoma of the kidney. METHODS: The clinical features,
      histological and immunohistochemical findings were analyzed in 3 cases of
      tubulocystic carcinoma of the kidney, along with review of the related
      literatures. RESULTS: Three patients were males with a mean age of 59 years old
      (range from 44 to 71 years). All presented with no symptom and their tumors were
      found during routine examination. The tumor size ranged from 1.5 to 5.0 cm in
      greatest dimension. The tumors were grossly well-circumscribed without capsules
      and exhibited a spongy cut surface. Microscopically, all three tumors were
      composed of tubules and cysts of varying sizes separated by thin fibrous septa.
      The epithelial lining cells were flat, cuboidal and columnar, with often a
      hobnail-like appearance characterized by abundant eosinophilic cytoplasm with
      prominent nucleoli. Two cases showed focal clear cytoplasm. One of the three
      cases coexisted with a papillary renal cell carcinoma. Immunohistochemically, all
      3 cases showed positivity for pan-CK, vimentin, CK19, CD10, P504S, and focal
      positivity for 34betaE12. Two cases showed focal positivity for CK7. CONCLUSIONS:
      Tubulocystic carcinoma of the kidney is a rare kidney neoplasm and occurs
      predominantly in males. The tumor is characterized by gross spongy appearance and
      microscopic cysts and tubules often lined by hobnail-like cells and separated by
      thin fibrotic stroma. The differential diagnosis mainly includes other lesions of
      the kidney that have a multicystic growth pattern.

PMID- 23157748
TI  - [MicroRNA383 regulates expression of PRDX3 in human medulloblastomas].
AB  - OBJECTIVE: To investigate the effects of microRNA-383 (miR-383) on PRDX3 gene
      expression, cell proliferation and apoptosis of human medulloblastma. METHODS:
      PRDX3 and miR-383 RNA expression was detected by real-time quantitative RT-PCR in
      human medulloblastoma tumor tissue samples, Daoy cell line and normal brain
      tissue samples. Western blot was used to detect protein expression of PRDX3.
      Synthetic miR-383 mimics were transfected into Daoy cells by lipofectamine. Using
      Cell Counting Kit-8 (CCK-8) method, flow cytometry was used to investigate the
      cell proliferation and apoptosis, cells reactive oxgen species(ROS),
      mitochondrial membrane potential changes in each experimental groups. RESULTS: Of
      15 cases of human medulloblastoma tumor, 13 cases had miR-383 expression levels
      significantly lower than that of normal brain tissue, and 14 had PRDX3 mRNA
      expression levels significantly higher than that of normal brain tissue. The
      expression levels of miR-383 and PRDX3 in Daoy cells were 0.353 and 1.315 times
      than those of normal brain tissue, respectively. The protein expression levels of
      PRDX3 were higher in human medulloblatoma tumors and Daoy cells than that of
      normal brain tissue. Transfected miR-383 mimics increased the expression level of
      miR-383 after 24 h and 48 h was significantly higher than that of the control. In
      contrast, PRDX3 gene mRNA and protein expression levels were significantly
      decreased at 48 h compared with the control group. Using CCK-8 assay, the cell
      proliferation rate in the experimental group was significantly lower than that of
      the control group (P < 0.05). Annexin V-FITC assay demonstrated that early
      apoptosis rate of the experimental group (11.60 +/- 0.30)% was significantly
      higher than those of the control group (2.3 +/- 0.20)% and negative control group
      (10.37 +/- 0.25)% (P = 0.000) after 48 h of transfection. The intracellular ROS
      levels after transfection at 24 and 48 h significantly increased than those of
      the control group. Mitochondrial membrane potential level at 24 h after
      transfection significantly decreased, comparing with the blank control group and
      the negative control group. CONCLUSIONS: Compared with normal brain tissue,
      decreased expression of miR-383 but elevated expression of PRDX3 are
      medulloblastoma tumour and Daoy cell lines. Up-regulation of miR-383 knockdowns
      the expression of PRDX3, inhibits proliferation and promotes apoptosis of Daoy
      cells, leading to increased intracellular ROS and decreased levels of
      mitochondrial membrane potential.

PMID- 23157749
TI  - [Effects of KIAA0101 expression on proliferation and invasion of gastric
      carcinoma MKN-45 cells].
AB  - OBJECTIVE: To investigate the expression of KIAA0101 protein in gastric carcinoma
      cells, and to explore the effects of its down-regulation on the cell
      proliferation, cell cycle and invasion. METHODS: Western blot was used to detect
      KIAA0101 protein expression in three gastric carcinoma cell lines including MKN
      28, SGC-7901 and MKN-45. KIAA0101 siRNA and control siRNA were utilized to
      transfect MKN-45 cells, respectively. CCK-8 was used to analyze the changes of
      cell proliferation, and flow cytometry to examine the changes of cell cycle
      distribution. Finally, Boyden chamber was used to detect the ability of cell
      invasion. RESULTS: Relative level of KIAA0101 protein in MKN-45 cells was
      significantly higher than those in MKN-28 and SGC-7901 cells, and there was
      significant difference among the three cell lines (P < 0.05). The result of CCK-8
      study demonstrated that, compared with untreated group and control siRNA group,
      the proliferation of MKN-45 cells in KIAA0101 siRNA group was significantly
      inhibited (P < 0.05). Additionally, the result of cell cycle analysis revealed
      that the percentage of cell number in G(0)/G(1) phase in KIAA0101 siRNA group
      [(61.47 +/- 0.89)%] was significantly higher than those in untreated group
      [(47.43 +/- 0.85)%] and control siRNA group [(48.43 +/- 0.73)%; F = 271.653, P =
      0.000]. Further, Boyden chamber assay showed that the cell numbers migrated to
      Matrigel in KIAA0101 siRNA group (61.51 +/- 4.76) were significantly lower than
      those in untreated group (138.74 +/- 10.16) and control siRNA group (132.93 +/-
      11.25; F = 65.949, P = 0.000). CONCLUSIONS: Down-regulation of KIAA0101
      expression leads to an inhibition of cell proliferation, cell cycle and cell
      invasion. It may provide a novel target for the treatment of patients with
      gastric carcinoma.

PMID- 23157750
TI  - [Study of clinicopathologic features and p53 gene alterations in renal
      epithelioid angiomyolipoma].

PMID- 23157751
TI  - [Hyalinizing trabecular tumor of thyroid: a clinicopathologic study].

PMID- 23157752
TI  - [Application and value of fluorescence quantitative PCR in detecting
      Mycobacterium tuberculosis in paraffin embedded specimens].

PMID- 23157753
TI  - [Fever of unknown origin in a long-term bed-ridden patient].

PMID- 23157754
TI  - [Thallium poisoning: report of an autopsy case].

PMID- 23157755
TI  - [Primary visceral myopathy: report of a case].

PMID- 23157756
TI  - [Significance of molecular technology in diagnosis and therapy of non-small-cell
      lung cancer].

PMID- 23157757
TI  - [Role of autophagy and apoptosis in tumor].

PMID- 23157758
TI  - Research collaboration with 2-1-1 to eliminate health disparities: an
      introduction.

PMID- 23157759
TI  - Reach, effectiveness, and connections: the case for partnering with 2-1-1 to
      eliminate health disparities.

PMID- 23157760
TI  - Health research and surveillance potential to partner with 2-1-1.

PMID- 23157761
TI  - Use of cancer control referrals by 2-1-1 callers: a randomized trial.
AB  - BACKGROUND: Callers to 2-1-1 have greater need for and lesser use of cancer
      control services than other Americans. Integrating cancer risk assessment and
      referrals to preventive services into 2-1-1 systems is both feasible and
      acceptable to callers. PURPOSE: To determine whether callers will act on these
      referrals. METHODS: In a randomized trial, 2-1-1 callers (n=1200) received
      standard service and those with at least one cancer risk factor or need for
      screening were assigned to receive verbal referrals only, verbal referrals + a
      tailored reminder mailed to their home, or verbal referrals + a telephone health
      coach/navigator. All data were collected from June 2010 to March 2012 and
      analyzed in March and April 2012. RESULTS: At 1-month follow-up, callers in the
      navigator condition were more likely to report having contacted a cancer control
      referral than those receiving tailored reminders or verbal referrals only (34% vs
      24% vs 18%, respectively; n=772, p<0.0001). Compared to verbal referrals only,
      navigators were particularly effective in getting 2-1-1 callers to contact
      providers for mammograms (OR=2.10, 95% CI=1.04, 4.22); Paps (OR=2.98, 95%
      CI=1.18, 7.54); and smoking cessation (OR=2.07, 95% CI=1.14, 3.74). CONCLUSIONS:
      Given the extensive reach of 2-1-1s and the elevated risk profile of their
      callers, even modest response rates could have meaningful impact on population
      health if proactive health referrals were implemented nationally.

PMID- 23157762
TI  - Monitoring unmet needs: using 2-1-1 during natural disasters.
AB  - BACKGROUND: Hurricanes Katrina and Rita struck the Gulf Coast forcing
      unprecedented mass evacuation and devastation. Texas 2-1-1 is a disaster
      communication hub between callers with unmet needs and community services at
      disaster sites and evacuation destinations. PURPOSE: To describe the location and
      timing of unmet disaster needs collected in real-time through Katrina-Rita
      disaster phases. METHODS: In 2008-2010, a total of 25 data sets of Texas 2-1-1
      calls from August-December 2005 were recoded and merged. In 2011-2012, analysis
      was performed of unmet need types, with comparisons over time and location;
      mapping was adjusted by population size. RESULTS: Of 635,983 total 2-1-1 calls
      during the study period, 65% included primary disaster unmet needs:
      housing/shelter (28%); health/safety (18%); food/water (15%); transportation/fuel
      (4%). Caller demand spiked on Mondays, decreasing to a precipitous drop on
      weekends and holidays. Unmet needs surged during evacuation and immediate
      disaster response, remaining at higher threshold through recovery. Unmet need
      volume was concentrated in metropolitan areas. After adjusting for population
      size, "hot-spots" showed in smaller evacuation destinations and along evacuation
      routes. CONCLUSIONS: New disaster management strategies and policies are needed
      for evacuation destinations to support extended evacuation and temporary or
      permanent relocation. Planning and monitoring disaster resources for unmet needs
      over time and location could be targeted effectively using real-time 2-1-1 call
      patterns. Smaller evacuation communities were more vulnerable, exhausting their
      limited resources more quickly. Emergency managers should devise systems to more
      quickly authorize vouchers and reimbursements. As 2-1-1s expand and coordinate
      disaster roles nationwide, opportunities exist for analysis of unmet disaster
      needs to improve disaster management and enhance community resiliency.

PMID- 23157763
TI  - Public broadcasting, media engagement, and 2-1-1: using mass communication to
      increase the use of social services.
AB  - BACKGROUND: The 2008-2009 subprime mortgage crisis was catastrophic, not only for
      the global economy but for families across the social spectrum. The resultant
      economic upheaval threatened the livelihoods, well-being, and health of many
      citizens, who were often unsure where to turn for help. At this critical
      juncture, public broadcasting stations worked to connect viewers to support
      resources through 2-1-1. PURPOSE: This study was designed to evaluate the ability
      of public broadcasting to increase the use of information and referral services.
      METHODS: Autoregressive integrated moving average (ARIMA) modeling and regression
      analysis document the relationship between public broadcasting initiatives and 2
      1-1 call volume in 35 highly affected U.S. markets. Time-series data from St.
      Louis MO were collected and analyzed in 2008. Station-level data from across the
      nation were collected during 2009-2010 and analyzed in 2010. RESULTS: ARIMA
      results show a distinct linkage between the timing and duration of Channel 9 in
      St. Louis MO (KETC) programming and a subsequent (approximately 400%) increase in
      2-1-1 calls regarding financial services and assistance. Regression path analysis
      not only found evidence of this same effect nationally but also showed that
      differences in the broadcaster's orientation and approach mediated effects.
      Specifically, stations' orientations toward engagement were mediated through
      strong outreach strategies to increase 2-1-1 use. CONCLUSIONS: This study
      documents the ability of public broadcasting to help citizens in need connect
      with social resources through 2-1-1 services. By focusing attention on the
      mortgage crisis and its attendant consequences, and by publicizing 2-1-1 services
      as a gateway to supportive resources, public broadcasters fostered linkages
      between those in need and social resources. Moreover, the level of a station's
      commitment to engaging citizens had a strong bearing on the success of its
      programming initiatives and community partnerships with organizations such as 2-1
      1.

PMID- 23157764
TI  - Healthcare navigation service in 2-1-1 San Diego: guiding individuals to the care
      they need.
AB  - BACKGROUND: Connecting vulnerable populations to healthcare and health-related
      services remains a challenge. In San Diego County, California, many individuals
      are unaware that they are eligible for assistance, and community-based healthcare
      providers often do not have a single, reliable point of access for information on
      available programs. PURPOSE: This paper describes how 2-1-1 San Diego worked with
      community partners to develop and implement a Healthcare Navigation Program.
      Navigators provide information about health insurance coverage, prescription
      assistance, and food assistance for low-income households and assist clients with
      transportation, appointment scheduling, child/elder care, and personal finance.
      METHODS: The 2-1-1 agents collected demographic, healthcare access, and program
      participation data as part of routine service. Participants in the Healthcare
      Navigation Program also completed a follow-up satisfaction survey. Data were
      collected July to December 2011, and analyzed in 2012. RESULTS: The program has
      resulted in increased enrollment of eligible individuals in California's
      Supplemental Nutrition Assistance Program and Medicaid, and a high percentage of
      callers reported satisfaction with the program and use of the referral
      information they received. CONCLUSIONS: The health-related programs of 2-1-1 San
      Deigo demonstrate the ability of this platform to support improvements in health
      and healthcare access.

PMID- 23157766
TI  - Managing Toronto citywide health crises through 2-1-1 services.
AB  - Information and referral systems such as 2-1-1 can be key partners in responding
      to community-wide health crises and other emergency and disaster events. This
      paper describes the experience of Toronto 2-1-1 dealing with the 2003 severe
      acute respiratory syndrome (SARS) epidemic and later that year the Great
      Northeastern Blackout. It shares five lessons learned from these experiences and
      describes how they have shaped the current approach to emergency and disaster
      response at Toronto 2-1-1 (now 2-1-1 Central Region Ontario).

PMID- 23157765
TI  - Developmental and autism screening through 2-1-1: reaching underserved families.
AB  - BACKGROUND: Developmental disorders, including autism spectrum disorders (ASDs),
      are increasing in prevalence. Early identification is necessary for early
      intervention, which is critical for reducing challenges and lifetime costs,
      especially for ASDs. Because not all children have equal access to developmental
      and autism screening through primary care settings, nontraditional methods are
      needed to reach underserved populations. PURPOSE: In this proof-of-concept study,
      the 2-1-1 Los Angeles County Developmental Screening Project (2-1-1 LA Project)
      provided developmental and autism screening by telephone in a population of low
      income and racially and ethnically diverse children. METHODS: Aggregate data were
      reviewed for 2845 children who were screened for developmental delays using the
      Parents' Evaluation of Developmental Status (PEDS) instrument and/or autism using
      the Modified Checklist for Autism in Toddlers (M-CHAT) instrument between
      September 1, 2009, and October 31, 2011. RESULTS: Data analysis was conducted
      December 2011 through February 2012. A majority of children (56%) screened with
      the PEDS had a moderate to high risk of developmental delays, including 28.2%
      classified as high-risk, which indicates need for further evaluation. Among 1605
      children screened with the M-CHAT, 21.2% had an elevated risk of ASDs. Follow-up
      care coordination was provided for 2625 children to facilitate completion of
      referrals for diagnostic evaluation, early childhood education, and other
      developmental or behavioral needs. CONCLUSIONS: The project's approach enhanced
      access to screenings and referral uptake in a population of children that may
      have difficulty accessing primary care. Findings suggest the potential of
      nontraditional developmental screening models.

PMID- 23157767
TI  - Exploring 2-1-1 service requests as potential markers for cancer control needs.
AB  - BACKGROUND: Delivering health information and referrals through 2-1-1 is
      promising, but these systems need efficient ways of identifying callers at
      increased risk. PURPOSE: This study explores the utility of using 2-1-1 service
      request data to predict callers' cancer control needs. METHODS: Using data from a
      large sample of callers (N=4101) to United Way 2-1-1 Missouri, logistic
      regression was used to examine the relationship between caller demographics and
      type of service request, and cancer control needs. RESULTS: Of six types of
      service requests examined, three were associated with one or more cancer control
      needs. Two of the service request types were associated also with health
      insurance status. CONCLUSIONS: Findings suggest routinely collected 2-1-1 service
      request data may be useful in helping to efficiently identify callers with
      specific cancer prevention and control needs. However, to apply this approach in
      2-1-1 systems across the country, further research and ongoing surveillance is
      necessary.

PMID- 23157768
TI  - Toronto's 2-1-1 healthcare services for immigrant populations.
AB  - BACKGROUND: Although access to information on health services is particularly
      important for recent immigrants, numerous studies have shown that their use of
      information and referral services is limited. This study explores the role played
      by 2-1-1 Toronto in supporting recent immigrants. PURPOSE: The study objectives
      were to (1) understand whether 2-1-1 Toronto is reaching and supporting recent
      immigrants and (2) gain a better appreciation of the information needs of this
      population group. METHODS: A phone survey was conducted in 2005-2006 to collect
      information on 2-1-1 users' characteristics and levels of satisfaction. Survey
      data were compared (in 2006) with census data to assess their representativeness.
      To achieve Objective 2, semistructured qualitative interviews were conducted and
      analyzed in 2006-2007, with a subset of Spanish-speaking callers. RESULTS: Recent
      immigrants were overrepresented among 2-1-1 callers. However, the survey
      population was substantially younger and had higher levels of formal education
      than the general population. Health-related queries represented almost one third
      of the total. The survey showed very high levels of satisfaction with the
      service. Many interviewees described their first experiences with the Canadian
      healthcare system negatively. Most of them had relied on disjointed, low-quality
      information sources. They trusted 2-1-1 but had discovered it late. CONCLUSIONS:
      Results are mixed in terms of 2-1-1's support to immigrants. A significant
      percentage of users do not take full advantage of the service. The service could
      become the information "entry point" for recent immigrants if it was able to
      reach them early in the resettlement process. Proactive, community-oriented work
      and a more creative use of technology could help.

PMID- 23157769
TI  - A 2-1-1 research collaboration: participant accrual and service quality
      indicators.
AB  - BACKGROUND: In times of crises, 2-1-1 serves as a lifeline in many ways. These
      crises often cause a spike in call volume that can challenge 2-1-1's ability to
      meet its service quality standards. For researchers gathering data through 2-1
      1s, a sudden increase in call volume might reduce accrual as 2-1-1 has less time
      to administer study protocols. Research activities imbedded in 2-1-1 systems may
      affect directly 2-1-1 service quality indicators. PURPOSE: Using data from a 2-1
      1 research collaboration, this paper examines the impact of crises on call volume
      to 2-1-1, how call volume affects research participant accrual through 2-1-1, and
      how research recruitment efforts affect 2-1-1 service quality indicators.
      METHODS: t-tests were used to examine the effect of call volume on research
      participant accrual. Linear and logistic regressions were used to examine the
      effect of research participant accrual on 2-1-1 service quality indicators. Data
      were collected June 2010-December 2011; data were analyzed in 2012. RESULTS:
      Findings from this collaboration suggest that crises causing spikes in call
      volume adversely affect 2-1-1 service quality indicators as well as accrual of
      research participants. Administering a brief (2-3 minute) health risk assessment
      did not affect service quality negatively, but administering a longer (15-18
      minute) survey had a modest adverse effect on these indicators. CONCLUSIONS: In 2
      1-1 research collaborations, both partners need to understand the dynamic
      relationship among call volume, research accrual, and service quality and adjust
      expectations accordingly. If research goals include administering a longer
      survey, increased staffing of 2-1-1 call centers may be needed to avoid
      compromising service quality.

PMID- 23157770
TI  - Human papillomavirus vaccine: 2-1-1 helplines and minority parent decision
      making.
AB  - BACKGROUND: Research is needed to understand parental factors influencing human
      papillomavirus (HPV) vaccination, particularly in groups with a higher burden of
      cervical cancer. PURPOSE: To determine correlates of HPV vaccination among a
      sample of low-income parents of age-eligible daughters (aged 9-17 years) who
      called the 2-1-1 Helpline. Secondary analyses describe potential differences in
      HPV vaccination correlates by Hispanic and black parent groups, in particular.
      METHODS: This 2009 cross-sectional feasibility survey of cancer prevention needs
      was conducted in Houston at the 2-1-1 Texas/United Way Helpline. In 2012, to
      examine the association between parental psychosocial, cognitive, and decisional
      factors and HPV vaccination uptake (one or two doses), bivariate and
      multivariable logistic regression analyses were conducted for minority parents
      and for Hispanic and black parent groups, separately. RESULTS: Lower rates of HPV
      vaccination uptake were reported among minority daughters of 2-1-1 callers (29%
      overall) compared with national and Texas rates. In final adjusted analysis,
      factors positively associated with HPV vaccination uptake included being offered
      the vaccination by a doctor or nurse, belief that the vaccine would prevent
      cervical cancer, and Hispanic ethnicity. Secondary analyses detected differences
      in factors associated with vaccination in Hispanic and black groups. CONCLUSIONS:
      Findings indicate low levels of vaccination among 2-1-1 callers. Increased
      understanding of determinants of HPV vaccination in low-income minority groups
      can guide interventions to increase coverage. Because 2-1-1 informational and
      referral services networks reach populations considered medically underserved, 2
      1-1 can serve as a community hub for informing development of and implementing
      approaches aimed at hard-to-reach groups.

PMID- 23157771
TI  - A review of the role of cost-benefit analyses in 2-1-1 diffusion.
AB  - CONTEXT: The 2-1-1 helpline is a social services innovation that has spread
      rapidly throughout the U.S. Policy diffusion theory suggests that policymakers
      seek to reduce uncertainty by anticipating the effects of a proposed innovation
      through tools such as cost-benefit analyses. Few policy diffusion studies have
      examined use of information, such as cost-benefit analyses, in the diffusion
      process. The purpose of this study is to examine how cost-benefit analyses were
      used during the rapid diffusion of 2-1-1 across states. The paper also describes
      components of 2-1-1 cost-benefit analyses. EVIDENCE ACQUISITION: In 2011, cost
      benefit analyses of 2-1-1 and substantive citations of them were identified
      through scholarly key word searches using Academic Search Premier and Web of
      Science, general Internet searches using Google search terms, and communications
      with academicians and 2-1-1 practitioners through personal contact and e-mail
      discussion groups. To be included in this study, documents had to be related to 2
      1-1 helplines, present information about their costs and benefits, and be formal
      documents. The documents were catalogued and analyzed for cost-benefit analyses
      or references to analyses, and stated purpose. EVIDENCE SYNTHESIS: Of the 19
      documents that met eligibility inclusion criteria, nine were original cost
      benefit analyses and ten referenced analyses conducted for other jurisdictions.
      CONCLUSIONS: The diffusion of 2-1-1 helplines in the U.S. has been influenced by
      interjurisdictional exchange of cost-benefit analyses, in both the creation of
      original analyses and/or the referencing of previous work.

PMID- 23157772
TI  - Navigating healthcare reform: a role for 2-1-1.

PMID- 23157773
TI  - Connecting eHealth with 2-1-1 to reduce health disparities.

PMID- 23157774
TI  - Guiding principles for collaborative research with 2-1-1.

PMID- 23157775
TI  - Advancing collaborative research with 2-1-1 to reduce health disparities:
      challenges, opportunities, and recommendations.

PMID- 23157776
TI  - Impact of sunlight and humic acid on the deposition kinetics of aqueous fullerene
      nanoparticles (nC60).
AB  - Nanoparticle transport in natural settings is complex due to interactions with
      the surrounding environment. In this study, the impact of UVA irradiation and
      humic acid (HA) on deposition of aqueous fullerene nanoparticles (nC60) on a
      silica surface as a surrogate for natural sediments was studied using packed
      column experiments and quartz crystal microbalance with dissipation monitoring
      under various solution conditions. Surface oxidation of nC60 induced by UVA
      irradiation greatly retarded its deposition due to the increased negative surface
      charge and hydrophilicity. Dissolved HA, once adsorbed onto the nC60 surface,
      also hindered its deposition mainly through steric hindrance forces. The extent
      of this effect depended on the properties and the amount of HA adsorbed, which is
      a function of ionic strength and HA concentration. HA has limited adsorption on
      UVA-irradiated nC60 and is expected to play a less important role in its
      stability. HA immobilized onto the silica surface had a variable effect on nC60
      deposition, depending on the complex interplay of Derjaguin-Landau-Verwey
      Overbeek (DLVO) and non-DLVO interactions such as electrostatic interaction,
      steric hindrance, and hydrogen bonding as well as HA molecular conformation.
      These results highlight the importance of environment-induced changes in nC60
      surface chemistry in its fate and transport in aquatic environments.

PMID- 23157777
TI  - 'Shiny white streaks' in lichen amyloidosis: a clue to diagnosis.

PMID- 23157778
TI  - A case of mosaic Ehlers-Danlos syndrome.
AB  - Ehlers-Danlos syndrome (EDS) is a group of inherited connective tissue disorders.
      The clinical manifestations are heterogeneous and usually generalised. We present
      a case of mosaic EDS, an extremely rare variant. Our patient presented with a
      single localised patch of EDS affecting her upper left thigh.

PMID- 23157779
TI  - Infantile digital fibromatosis: a rare tumour of infancy. Report of five cases.
AB  - Infantile digital fibromatosis (IDF) is a rare tumour of infancy with a typical
      clinical presentation and characteristic histopathological findings. Despite an
      alarming appearance, IDF does not cause deep infiltration or metastasis. The
      traditional approach of surgical resection was recently challenged by increasing
      evidence of self regression in months or years. We describe the clinical history
      of five patients with IDF that were followed in our departments for 5 years.

PMID- 23157780
TI  - Cutaneous metastasis from lung cancer: retrospective analysis of 30 patients.
AB  - Lung carcinoma is one of the most frequent sources of skin metastases in male
      patients. Our objective was to analyse the clinical and pathological features of
      30 patients with skin metastases from lung carcinoma. Cutaneous biopsies codified
      as 'skin metastasis from lung carcinoma' during 1988-2009 at Bellvitge Hospital
      (Barcelona, Spain) were reviewed. The histological types of 30 lung carcinomas
      (29 men, 1 woman) were squamous cell carcinoma (10 cases), undifferentiated
      carcinoma (7), adenocarcinoma (6), small cell carcinoma (5) and large cell
      carcinoma (2). The most frequent clinical presentation was as a solitary nodule
      (16 cases), and the most frequent site was the head (13 cases). Cutaneous
      metastases were present at the time of diagnosis of the lung primary tumour in
      66% of cases. Skin biopsy might be helpful to establish the histological type of
      tumour, and thus help with therapeutic decision-making. Cutaneous metastases from
      lung cancer remain a poor prognostic feature.

PMID- 23157781
TI  - Poor efficacy of oral tacrolimus in the treatment of severe generalized atopic
      eczema in adults: a small retrospective case series.
AB  - We report a small, but novel case series of four adults with severe generalized
      atopic eczema (AE) not responsive to several other immunomodulatory therapies,
      who were treated with oral tacrolimus (5 mg twice-daily). Three of the four
      patients failed therapy with systemic tacrolimus, despite two of these showing an
      initial clinical response; the fourth patient remains on tacrolimus monotherapy
      with good control of skin disease. Although oral tacrolimus was well-tolerated in
      this small group of adults, the clinical efficacy in this series for severe AE
      was poor. Tacrolimus may yet have a role in less severe disease, but larger
      prospective studies are required to qualify its place as a treatment option in
      AE.

PMID- 23157782
TI  - Sacroiliitis secondary to isotretinoin.
AB  - Reported is the case of a 17-year old male with sacroiliitis confirmed by
      magnetic resonance imaging (MRI) while undergoing isotretinoin treatment for acne
      vulgaris. The cessation of isotretinoin and symptomatic treatment resolved the
      symptoms within 6 weeks, with no signs of sacroiliitis on repeat MRI 10 months
      later. The temporal association of disease onset and commencement of isotretinoin
      along with rapid recovery on withdrawal supports the role of isotretinoin in this
      case.

PMID- 23157783
TI  - Toxic epidermal necrolysis-like subacute cutaneous lupus erythematosus.
AB  - Toxic epidermal necrolysis (TEN)-like presentations have been described in non
      drug-induced settings. We describe a case of subacute cutaneous lupus
      erythematosus (SCLE) in a 53-year old woman, which evolved into a TEN-like
      presentation over the course of 4 weeks. The patient responded rapidly to
      treatment with intravenous methylprednisolone. This article draws attention to
      features that may be used to differentiate classical TEN from TEN-like SCLE.

PMID- 23157784
TI  - Photographic artefact simulating regressing melanocytic lesion: a potential
      pitfall of total body photography.

PMID- 23157785
TI  - Dermatoscopy of Grover's disease and solitary acantholytic dyskeratoma shows a
      brown, star-like pattern.

PMID- 23157786
TI  - Cutaneous tuberculosis simulating lymphocutaneous sporotrichosis.

PMID- 23157788
TI  - Calcinosis cutis following contact with calcium chloride solution.
AB  - Calcinosis cutis is the deposition of insoluble calcium in the cutaneous tissue.
      Calcinosis cutis can be classified as metastatic, dystrophic, idiopathic or
      exogenous. We report a 48-year-old white man who was dismantling a portable ice
      skating rink when calcium chloride solution from the pipes spilt onto his
      clothing. Several days later, he started to develop mildly pruritic erythematous
      papules, some studded with white deposits and some with umbilication over the
      exposed areas corresponding to the spillage of the calcium chloride solution.
      Histological features revealed interstitial fibrohistiocytic reaction with
      calcium-encrusted degenerated collagen bundles in the dermis which was further
      confirmed by von Kossa stain. He was commenced on topical corticosteroid cream
      twice daily and the lesions cleared completely between 6 to 10 weeks.

PMID- 23157789
TI  - Generalized flare of pustular psoriasis induced by PEGylated interferon-alpha2b
      therapy for chronic hepatitis C.
AB  - New onset or exacerbation of psoriasis vulgaris has been reported in a small
      number of patients after interferon (IFN)-alpha therapy. Herein, we report a case
      of generalized flare of pustular psoriasis induced by PEGylated IFN-alpha2b (PEG
      IFN-alpha2b) in a 59-year-old woman with a 15-year history of pustular psoriasis
      and chronic hepatitis C. Interferon-alpha therapy was discontinued and the rash
      resolved after treatment with cyclosporin and systemic methylprednisolone. The
      potential side effect of PEG-IFN-alpha2b in inducing or exacerbating psoriasis
      should be kept in mind when treating patients with a history of psoriasis or
      pustular psoriasis.

PMID- 23157790
TI  - Drug-induced dermatomyositis after zoledronic acid.
AB  - A 57-year-old woman with prior exposure to bisphosphonates developed myalgia,
      proximal muscle weakness and lichenoid rash over the upper extremities and face 3
      days after infusion of zoledronic acid for the management of osteoporosis. The
      diagnosis of dermatomyositis was made on the basis of clinical, laboratory and
      histological findings. This is the first report of drug-induced dermatomyositis
      secondary to zoledronic acid.

PMID- 23157791
TI  - Pityriasis lichenoides et varioliformis acuta: a rare association with the
      measles, mumps and rubella vaccine.
AB  - The aetiology of pityriasis lichenoides (PL) is unknown. One major pathogenic
      theory suggests that PL is a lymphoproliferative disease or inflammatory reaction
      triggered by an antigenic stimulus, such as a virus or other infectious agent. We
      report the second case of PL et varioliformis acuta (PLEVA) occurring after
      measles vaccination and the first following the combined measles, mumps, rubella
      vaccination.

PMID- 23157792
TI  - Lipoid proteinosis presenting with an unusual nonsense Q32X mutation in exon 2 of
      the extracellular matrix protein 1 gene.
AB  - Lipoid proteinosis (LP) is a rare disorder characterized by extensive hyaline
      like deposits on the skin, mucous membranes and various internal organs with
      varying clinical manifestations. The disorder has been recently shown to result
      from loss-of-function mutations in the extracellular matrix protein 1 gene (ECM1)
      on 1Q21. The two cases reported here had typical clinical and histological
      features consistent with LP. Direct sequencing of amplified DNA from the second
      patient showed a single nucleotide substitution (C > T) at nucleotide 94 within
      exon 2 of the ECM1 gene, nonsense mutation Q32X. This is the second case reported
      of LP with involvement of exon 2 of ECM1.

PMID- 23157793
TI  - Febrile ulceronecrotic Mucha-Habermann disease: a case with systemic symptoms
      managed with subcutaneous methotrexate.
AB  - Febrile ulceronecrotic Mucha-Habermann disease (FUMHD) is a rare, idiopathic,
      acquired dermatosis that can affect all ages and ethnic groups. We present a 10
      year-old patient with FUMHD associated with arthritis and chronic fatigue,
      managed with methotrexate. Through our literature review, we also explore
      treatment protocols for a disease for which internationally standardized
      management is yet to be formulated.

PMID- 23157794
TI  - Development of cutaneous sarcoidosis during treatment with tumour necrosis alpha
      factor antagonists.
AB  - The use of tumour necrosis factor alpha (TNF-alpha) antagonists is increasing in
      the field of dermatology. These agents have been used for multiple inflammatory
      and immune skin conditions, but most notably, psoriasis. Adverse effects of anti
      TNF-alpha agents have been reported, including the paradoxical development of
      sarcoidosis. We present an unusual case of limited cutaneous sarcoidosis
      developing while the patient was on etanercept therapy, and a review of the
      current literature.

PMID- 23157795
TI  - Regrowth of black hair in two red-haired alopecia areata patients.
AB  - The occurrence of alopecia areata (AA) in a red-haired individual is considered
      to be rare. We report two cases of red-haired men who were afflicted with patch
      type AA. Astonishingly, the hair regrowth was coloured black, in contrast to the
      surrounding red hair, an event which has been reported only once in the past
      after cyclophosphamide administration. This phenomenon raises some interesting
      questions regarding the significance of pigmentation and the melanocortin-1
      receptor in AA pathogenesis.

PMID- 23157797
TI  - Expression of epithelial to mesenchymal transition-related markers in lymph node
      metastases as a surrogate for primary tumor metastatic potential in breast
      cancer.
AB  - BACKGROUND: Breast cancers are phenotypically and genotypically heterogeneous
      tumors containing multiple cancer cell populations with various metastatic
      potential. Aggressive tumor cell subpopulations might more easily be captured in
      lymph nodes metastases (LNM) than in primary tumors (PT). We evaluated mRNA and
      protein levels of master EMT regulators: TWIST1, SNAIL and SLUG, protein levels
      of EMT-related markers: E-cadherin, vimentin, and expression of classical breast
      cancer receptors: HER2, ER and PgR in PT and corresponding LNM. The results were
      correlated with clinicopathological data and patients outcomes. METHODS: Formalin
      fixed paraffin-embedded samples from PT and matched LNM from 42 stage II-III
      breast cancer patients were examined. Expression of TWIST1, SNAIL and SLUG was
      measured by reverse-transcription quantitative PCR. Protein expression was
      examined by immunohistochemistry on tissue microarrays. Kaplan-Meier curves for
      disease-free survival (DFS) and overall survival (OS) were compared using F-Cox
      test. Hazard ratios (HRs) with 95% confidence intervals (95% CI) were computed
      using Cox regression analysis. RESULTS: On average, mRNA expression of TWIST1,
      SNAIL and SLUG was significantly higher in LNM compared to PT (P < 0.00001 for
      all). Gene and protein levels of TWIST1, SNAIL and SLUG were highly discordant
      between PT and matched LNM. Increased mRNA expression of TWIST1 and SNAIL in LNM
      was associated with shorter OS (P = 0.04 and P = 0.02, respectively) and DFS (P =
      0.02 and P = 0.01, respectively), whereas their expression in PT had no
      prognostic impact. Negative-to-positive switch of SNAIL protein correlated with
      decreased OS and DFS (HR = 4.6; 1.1-18.7; P = 0.03 and HR = 3.8; 1.0-48.7; P =
      0.05, respectively). CONCLUSIONS: LNM are enriched in cells with more aggressive
      phenotype, marked by elevated levels of EMT regulators. High expression of TWIST1
      and SNAIL in LNM, as well as negative-to-positive conversion of SNAIL confer
      worse prognosis, confirming the correlation of EMT with aggressive disease
      behavior. Thus, molecular profiling of LNM may be used as surrogate marker for
      aggressiveness and metastatic potential of PT.

PMID- 23157798
TI  - Potential role of sleep in bipolar disorder.

PMID- 23157799
TI  - Sleep, psychiatric disorders and suicide.

PMID- 23157800
TI  - Nonconscious and conscious colour priming in schizophrenia: who's to tell?

PMID- 23157801
TI  - Response to Vakalopoulos' letter to the editor Re: Nonconscious and conscious
      color priming in schizophrenia.

PMID- 23157802
TI  - Imaging of infective endocarditis with cardiac CT angiography.
AB  - Infective endocarditis (IE) is a disease characterized by high rates of morbidity
      and mortality that can present with a spectrum of clinical and imaging findings.
      Cardiac-gated computed tomographic angiography (CTA) has been shown to be highly
      accurate in evaluation of both coronary artery disease and structural heart
      disease and is now considered an appropriate preoperative imaging modality in
      patients undergoing noncoronary cardiac surgery. This review discusses the use of
      cardiac-gated CTA in preoperative evaluation of patients with IE, with emphasis
      on imaging findings of valvular and perivalvular complications. Topics include
      technique tips specific to valve imaging with cardiac-gated CTA, potential
      benefits of cardiac-gated CTA compared with other imaging modalities such as
      echocardiography, limitations of imaging patients with IE with cardiac-gated CTA,
      and an overview of potential findings in patients with IE, including vegetations,
      valve perforations, perivalvular abscesses, perivalvular pseudoaneurysms, and
      fistulas. Throughout this review, cardiac-gated CTA findings of IE are presented
      with echocardiographic and operative correlation to emphasize that cardiac-gated
      CTA may in select cases provide incremental benefit in the preoperative
      assessment of patients with IE.

PMID- 23157803
TI  - Education-based health inequalities in 18,000 Norwegian couples: the Nord
      Trondelag Health Study (HUNT).
AB  - BACKGROUND: Education-based inequalities in health are well established, but they
      are usually studied from an individual perspective. However, many individuals are
      part of a couple. We studied education-based health inequalities from the
      perspective of couples where indicators of health were measured by subjective
      health, anxiety and depression. METHODS: A sample of 35,980 women and men (17,990
      couples) was derived from the Norwegian Nord-Trondelag Health Study 1995-97 (HUNT
      2). Educational data and family identification numbers were obtained from
      Statistics Norway. The dependent variables were subjective health (four-integer
      scale), anxiety (21-integer scale) and depression (21-integer scale), which were
      captured using the Hospital Anxiety and Depression Scale. The dependent variables
      were rescaled from 0 to 100 where 100 was the worst score. Cross-sectional
      analyses were performed using two-level linear random effect regression models.
      RESULTS: The variance attributable to the couple level was 42% for education, 16%
      for subjective health, 19% for anxiety and 25% for depression. A one-year
      increase in education relative to that of one's partner was associated with an
      improvement of 0.6 scale points (95% confidence interval = 0.5-0.8) in the
      subjective health score (within-couple coefficient). A one-year increase in a
      couple's average education was associated with an improvement of 1.7 scale points
      (95% confidence interval = 1.6-1.8) in the subjective health score (between
      couple coefficient). There were no education-based differences in the anxiety or
      depression scores when partners were compared, whereas there were substantial
      education-based differences between couples in all three outcome measures.
      CONCLUSIONS: We found considerable clustering of education and health within
      couples, which highlighted the importance of the family environment. Our results
      support previous studies that report the mutual effects of spouses on education
      based inequalities in health, suggesting that couples develop their socioeconomic
      position together.

PMID- 23157804
TI  - The MINT project--an evaluation of the impact of midwife teachers on the outcomes
      of pre-registration midwifery education in the UK.
AB  - OBJECTIVE: to explore the contribution of midwife teachers in preparing student
      midwives for competent practice. DESIGN: a three phase design using qualitative
      and quantitative approaches. Phase one involved UK wide on-line questionnaire
      surveys, phase two was a case study method in six UK approved education
      institutions and phase three was a diary study with newly qualified midwives.
      PARTICIPANTS: phase one included all UK Lead Midwives for Education (LMEs),
      midwife teachers and Local Supervising Authority Midwifery Officers; phase two
      participants were three year and shortened programme student midwives, midwife
      teachers, LMEs and programme leads from each of the four countries; and phase
      three included a sample of newly qualified midwives graduating from the case
      study sites and their preceptors and supervisors of midwives. FINDINGS: midwife
      teachers were valued for their unique and crucial role in supporting the
      application of knowledge to midwifery practice. Visibility and credibility were
      two key concepts that can explain the unique contribution of midwife teachers.
      These concepts included being able to support skills acquisition, understanding
      of contemporary midwifery practice, having a role in practice contexts and able
      to offer personal support. Visibility of teachers in practice was vital for
      students and mentors to assist students put their learning into practice and
      monitor learning and assessment decisions. CONCLUSIONS AND IMPLICATIONS FOR
      PRACTICE: given the complexity of midwifery education a team approach is
      essential in ensuring the effectiveness of these programmes. This requires a
      sufficient differentiation of midwife teacher roles to deliver the pre
      registration curriculum. A set of resource quality indicators is proposed to
      support midwife teacher teams achieving sufficient clinical and academic
      expertise to deliver effective education programmes.

PMID- 23157805
TI  - Clinically diagnosed depression and self-rated depressive state: prognostic
      ability of cardiac event for patients after myocardial infarction.

PMID- 23157806
TI  - Measles and Brugada pattern: a case report.

PMID- 23157807
TI  - C-reactive protein induces expression of matrix metalloproteinase-9: a possible
      link between inflammation and plaque rupture.
AB  - BACKGROUND: Matrix metalloproteases (MMPs) have been implicated in the
      pathogenesis of acute coronary syndromes (ACS). However, little is known about
      the mechanisms responsible for MMP expression in ACS. C-reactive protein (CRP)
      not only is an independent risk factor for cardiovascular events, but also may
      exert direct pro-atherosclerotic effects. Therefore, we aimed at determining
      whether CRP might induce MMP-9 in two different experimental conditions: 1)
      smooth muscle cells (SMCs) in vitro, and 2) patients with ACS. METHODS AND
      RESULTS: Effects of increasing concentrations of CRP on MMP-9 expression were
      evaluated in vitro in human SMCs. TIMP-1 protein expression, the selective
      inhibitor of MMP-9, was also evaluated. CRP dose-dependently induced MMP-9
      expression in SMCs by promoting MMP-mRNA transcription, as well as MMP-9
      secretion. In contrast, no differences were found for TIMP-1 protein expression.
      In vivo, MMP-9 and CRP levels were measured in blood samples obtained from the
      aorta (Ao) and the coronary sinus (Cs) of patients with normal coronary arteries
      (controls, n=21), stable angina (n=24), and ACS (n=30). Both MMP-9 and CRP plasma
      levels were significantly increased across the coronary circulation only in
      patients with ACS. Interestingly, a significant correlation between MMP-9 and CRP
      plasma levels was found. CONCLUSIONS: CRP induced MMP-9 expression and activity
      in human SMCs in culture; patients presenting with ACS have increased
      transcoronary plasma levels of MMP-9 and CRP with a significant correlation
      between these two markers. This may explain the heightened risk of coronary
      events in subjects with elevated levels of CRP.

PMID- 23157808
TI  - Adherence to protocol and determinants in ST-elevation myocardial infarction.

PMID- 23157809
TI  - 17beta-estradiol attenuates atherosclerosis development: the possible role of
      hydrogen sulfide.

PMID- 23157811
TI  - The diagnosis of myocardial infarction in the Wolff-Parkinson-White syndrome.

PMID- 23157810
TI  - Residual risk of cardiovascular mortality in patients with coronary heart
      disease: the EUROASPIRE risk categories.
AB  - BACKGROUND: The EUROASPIRE I, II and III surveys revealed high prevalences of
      modifiable risk factors in the high priority group of coronary patients all over
      Europe. The potential to further reduce coronary heart disease (CHD) morbidity
      and mortality rates is still considerable. We report here on the relative risk of
      cardiovascular disease (CVD) death associated with common modifiable risk factor
      levels based on the mortality follow-up of patients participating in the first
      two EUROASPIRE surveys. We also present a novel simple risk classification system
      (ERC) that can be used in the management of patients with existing CHD. METHODS:
      The study cohort consisted of a consecutive sample of CHD patients aged <= 70
      years from 12 European countries. Baseline data gathered in 1995-2000 through
      standardized methods, were linked to cardiovascular mortality in 5216 patients
      according to an accelerated failure time model. RESULTS: During 28,143 person
      years of follow-up, 332 patients died from cardiovascular disease denoting a CVD
      mortality risk of 12.3 per 1000 person-years in men and 10.2 per 1000 person
      years in women. In multivariate analysis, fasting glucose, total cholesterol and
      smoking emerged as the strongest independent modifiable predictors of
      cardiovascular mortality. CONCLUSIONS: The results of the mortality follow-up of
      the EUROASPIRE I and II CHD patients emphasize the continuing risk from elevated
      glucose and total cholesterol levels and underline the importance of smoking
      cessation in secondary prevention. The ERC risk tool that we developed may prove
      helpful to obtain these goals in the setting of secondary prevention.

PMID- 23157812
TI  - MicroRNA-1/133 targeted dysfunction of potassium channels KCNE1 and KCNQ1 in
      human cardiac progenitor cells with simulated hyperglycemia.

PMID- 23157813
TI  - Lipid profile and mortality after discharge of patients admitted with
      decompensated heart failure.

PMID- 23157814
TI  - Endothelial cell activation, reduced endothelial cell reparative capacity, and
      impaired endothelial-dependent vasodilation after anger provocation.

PMID- 23157815
TI  - Baroreflex sensitivity and heart rate variability are enhanced in patients with
      anorexia nervosa.

PMID- 23157816
TI  - Successful treatment of a long tapered lesion with two overlapping ABSORB
      bioresorbable vascular scaffolds of different diameters: evaluation by three
      dimensional optical coherence tomography.

PMID- 23157817
TI  - Primary cervical hydatid cyst: a rare occurrence.
AB  - Hydatid disease, a parasitic infection is caused by Echinococcus granulosus. It
      has serious impact on health and economy especially in countries where it is
      endemic. It occurs frequently in liver and lung. The disease is chronic and cyst
      can localize in different organs. A hydatid cyst occurrence in the head and neck
      is extremely rare. To know the distribution of disease can help in its control
      and prevention. We report a case of primary cervical hydatid cyst in 20 year old
      female. A high index of suspicion is required to diagnose hydatid cyst in rare
      locations like this. Hydatid cyst should be considered in differential diagnosis
      of benign swellings of head and neck region, so that it can be managed during
      surgery to prevent acute anaphylaxis. VIRTUAL SLIDES: The virtual slides' for
      this article can be found here:
      http://www.diagnosticpathology.diagnomx.eu/vs/4915595218376646.

PMID- 23157818
TI  - Modeling the impact of air, sea, and land travel restrictions supplemented by
      other interventions on the emergence of a new influenza pandemic virus.
AB  - BACKGROUND: During the early stages of a new influenza pandemic, travel
      restriction is an immediate and non-pharmaceutical means of retarding incidence
      growth. It extends the time frame of effective mitigation, especially when the
      characteristics of the emerging virus are unknown. In the present study, we used
      the 2009 influenza A pandemic as a case study to evaluate the impact of
      regulating air, sea, and land transport. Other government strategies, namely,
      antivirals and hospitalizations, were also evaluated. METHODS: Hong Kong arrivals
      from 44 countries via air, sea, and land transports were imported into a discrete
      stochastic Susceptible, Exposed, Infectious and Recovered (SEIR) host-flow model.
      The model allowed a number of latent and infectious cases to pass the border,
      which constitutes a source of local disease transmission. We also modeled
      antiviral and hospitalization prevention strategies to compare the effectiveness
      of these control measures. Baseline reproduction rate was estimated from routine
      surveillance data. RESULTS: Regarding air travel, the main route connected to the
      influenza source area should be targeted for travel restrictions; imposing a 99%
      air travel restriction delayed the epidemic peak by up to two weeks. Once the
      pandemic was established in China, the strong land connection between Hong Kong
      and China rendered Hong Kong vulnerable. Antivirals and hospitalization were
      found to be more effective on attack rate reductions than travel restrictions.
      Combined strategies (with 99% restriction on all transport modes) deferred the
      peak for long enough to establish a vaccination program. CONCLUSION: The findings
      will assist policy-makers with decisions on handling similar future pandemics. We
      also suggest regulating the extent of restriction and the transport mode, once
      restriction has been deemed necessary for pandemic control. Although travel
      restrictions have yet to gain social acceptance, they allow time for mitigation
      response when a new and highly intrusive virus emerges.

PMID- 23157819
TI  - Metabolism of energy substrates of in vitro and in vivo derived embryos from ewes
      synchronized and super ovulated with norgestomet and porcine follicle stimulating
      hormone.
AB  - The synchronization and ovulatory responses of Sangsari cross bred ewes and
      metabolism of energy substrates in 8-cell stage embryos to hatched blastocysts
      stage produced in vitro or in vivo were investigated. Ewes were assigned randomly
      to receive 37.5 IU of porcine follicle stimulating hormone (FSH-P) daily for the
      3 days preceding implant removal (Day 0). Synchronization of estrus was carried
      out using a 1.5 mg norgestomet (Crestar) ear implant for 12 days. Ewes in estrus
      were mated two to three times with rams of proven fertility. At the time of first
      mating each ewe was administered 1000 IU of human chorionic gonadotrophin (hCG)
      to induce ovulation. Surgical embryo recovery was performed on Days 4 and 6 after
      onset of estrus (Day 0) and recovered embryos were subjected to comparative
      metabolism studies with in vitro derived embryos at the same stage of
      development. The number of corpora lutea (CL), unovulated follicles and overall
      ovarian activity were recorded for each ewe during the breeding and non-breeding
      seasons. While the pattern of oxidation was similar among in vitro and in vivo
      derived embryos, a low pyruvate to lactate ratio was the preferred substrate of
      embryos derived in vitro. A high level of production of CO2 and lactate resulted
      from a stress response to the suboptimal culture environment. The first marked
      increase in the metabolism of glucose by ovine embryos was detected in compact
      morula stage, but there was no significant increase in the oxidation of glucose
      after the morula stage. Two different concentrations of glucose were compared,
      but this did not affect metabolism. However, the rate of incorporation and
      metabolism of glucose tended to be higher at the 0.56 mmol/L glucose dosage.

PMID- 23157820
TI  - A case study approach to investigating end-of-life decision making in an acute
      health service.
AB  - AIM: To identify end-of-life (EOL) decision making processes for patients with
      non-cancer illnesses in a major metropolitan hospital. METHODS: A retrospective
      review using a case study framework of 47 randomly selected patient records over
      a 6-month period explored issues in EOL care planning. RESULTS: Reviewed charts
      represented 53% of total deaths in the study period. All patients (aged 66-99)
      had co-morbid conditions. In 64%, the first record of EOL discussions occurred in
      the last 24h of life. Four case groups were identified, ranging from a clear plan
      developed with patient/family involvement and fully implemented, to no plan with
      minimal patient/family involvement in decision making. Factors related to clearer
      EOL care planning according to expressed patient wishes included multiple
      previous admissions, shorter hospitalisations at EOL, living with a relative and
      involvement of family in decisions about care. CONCLUSION: This study has shown
      that the development and effective implementation of EOL plans is associated with
      the active involvement of both family members and health professionals. It also
      draws attention to the risks of delaying EOL discussions until late in the
      illness trajectory or later in life as well as pointing to challenges in acting
      on EOL developed outside the hospital environment.

PMID- 23157821
TI  - Predictors of 1-month and 1-year neurocognitive functioning from the UCLA
      longitudinal mild, uncomplicated, pediatric traumatic brain injury study.
AB  - Although more severe brain injuries have long been associated with persisting
      neurocognitive deficits, an increasing body of literature has shown that
      children/adolescents with single, uncomplicated mild traumatic brain injury
      (mTBI) do not exhibit long-lasting neurocognitive impairments. Nonetheless,
      clinical experience and our previous report (Babikian, 2011) showed that a
      minority of children/adolescents exhibit persistent cognitive problems using
      performance based measures following what appear to be relatively mild injuries.
      Predictors of poor neurocognitive outcomes were evaluated in 76 mTBI and 79 Other
      Injury subjects to determine the relative contributions of indices of injury
      severity, clinical symptomatology, demographic factors, and premorbid functioning
      in predicting 1-month and 12-month neurocognitive impairment on computerized or
      paper and pencil measures. Injury severity indicators or type of injury (head vs.
      other body part) did not predict either 1-month or 12-month cognitive impairment
      status. Rather, premorbid variables that antedated the injury (parental
      education, premorbid behavior and/or learning problems, and school achievement)
      predicted cognitive impairments. When post-injury neurocognitive impairments are
      observed in survivors of mild injuries (head or other body part), a sound
      understanding of their etiology is critical in designing appropriate intervention
      plans. Clinical and research implications are discussed.

PMID- 23157822
TI  - [Standardization of molecular diagnostic tools assures validation of the
      results].

PMID- 23157823
TI  - [Mutations of KRAS and BRAF in Chinese patients with colorectal carcinoma:
      analyses of 966 cases].
AB  - OBJECTIVE: To identify the mutation rate of KRAS and BRAF in Chinese patients
      with colorectal carcinoma (CRC), and to analyze the associations between
      KRAS/BRAF mutations and patients' clinicopathological characteristics. METHODS:
      Tumor specimens were obtained from 966 CRC patients treated in Peking University
      Cancer Hospital from December 2008 to January 2012. Mutation analysis of KRAS
      (codons 12 and 13 of exon 2) and BRAF (exon 15) was conducted by direct
      sequencing. The relationships between gene mutations and clinicopathological
      characteristics were statistically analyzed. RESULTS: The mutation rates of KRAS
      and BRAF in Chinese CRC patients were 38.8% (375/966) and 4.4% (40/915),
      respectively. Among patients with wild-type KRAS, the mutation rate of BRAF was
      7.4% (40/540). KRAS and BRAF mutations were mutually exclusive. Eight mutation
      types of KRAS were detected in this study with three common types G12D, G12V and
      G13D. Three mutation types of BRAF were detected with the most common type V600E.
      KRAS mutation rate was significantly higher in female, well-differentiated and
      right side colon tumors (all P < 0.05). Also, the mutation rate in patients >= 65
      years was higher than that in patients < 65 years (P = 0.05). BRAF mutation rate
      was higher in poorly-differentiated and right side colon tumors (P < 0.05). No
      significant associations were observed between KRAS/BRAF mutations and tumor
      size, depth of invasion, lymph node metastasis and TNM staging (P > 0.05).
      CONCLUSIONS: In Chinese CRC patients, KRAS mutations are associated with gender,
      age, tumor differentiation and primary tumor sites, while BRAF mutation is only
      associated with tumor differentiation and primary tumor sites. The correlations
      between KRAS/BRAF mutations and patients' prognosis need further investigation.

PMID- 23157824
TI  - [KRAS and BRAF gene mutations in correlation with clinicopathologic features of
      colorectal carcinoma in Chinese].
AB  - OBJECTIVE: To retrospectively analyze KRAS and BRAF gene mutation features in
      Chinese colorectal cancer (CRC) and their clinicopathologic relationship.
      METHODS: 557 colorectal cancer cases were collected, including 325 colon cancer
      and 232 rectal cancer. PCR amplification and DNA sequencing were used to detect
      mutations in exon 2 of KRAS gene and exon 15 of BRAF gene mutation. RESULTS: (1)
      KRAS mutation was found in 40.4% (225/557) colorectal cancer. The most common
      mutation locations were in codon 12(79.1%, 178/225) and codon 13 (20.4%, 46/225).
      The most common mutation types were GGT > GAT (G12D) (37.8%, 85/225), GGT >
      GTT(G12V) (20.0%, 45/225) in codon 12 and GGC > GAC (G13D) in codon 13 (19.6%,
      44/225). These three point mutations accounted 77.3% (174/225) in total KRAS gene
      mutation cases. All cases showed only one of point mutation types. (2) Among 557
      CRC cases, KRAS mutation was significantly higher in female (46.2%, 92/199) than
      in man (37.2%, 133/358; P < 0.05). KRAS gene codon 13 mutation was higher in
      right colon cancer (11.3%, 12/106) than that in left colon cancer (4.8%, 6/124),
      but it didn't show any statistical significance (P > 0.05). (3) BRAF gene
      mutation was 5.1% (10/197) in colorectal cancer and 8/10 were the point mutation
      of GTG > GAG (V600E). Eight colorectal cancer cases with GTG > GAG (V600E) were
      not showing KRAS gene mutation. Both two cases with mutation on codon 600 (GTG >
      ATG, V600M) and codon 606 (GGG > AGT, G606S) showed codon 12 mutation of KRAS
      gene. (4) BRAF (V600E) gene mutation was higher in female (8.5%, 6/71) than that
      in male (1.6%, 2/126; P = 0.05); BRAF mutation in colon cancer (8.3%, 6/72) was
      higher than that in rectum cancer (2.1%, 2/94), but hadn't statistical
      significance (P > 0.05). CONCLUSIONS: (1) Codon 12, 13 in KRAS gene and codon 600
      in BRAF gene are the most common mutation points in Chinese colorectal cancer.
      KRAS and BRAF mutations are mutually exclusive. (2) KRAS and BRAF gene mutation
      is higher in female than that in male, suggesting that RAS-RAF-MAPK signal
      pathway is probably related to hormones directly or indirectly. (3) There is a
      trend that codon 13 mutation in KRAS and codon 600 mutation in BRAF in right
      colon cancer are higher than that in left colon cancer, respectively, however,
      which needs more cases to be further verified.

PMID- 23157825
TI  - [Detection of KRAS, BRAF, PIK3CA and EGFR gene mutations in colorectal
      carcinoma].
AB  - OBJECTIVE: To investigate the mutation frequencies of KRAS, BRAF, PIK3CA and EGFR
      genes that were effective on the targeted therapies in colorectal carcinoma.
      METHODS: The tissue specimens from 331 colorectal cancer patients were collected
      and subject to KRAS, BRAF, PIK3CA and EGFR mutation analysis. Paraffin-embedded
      tissue samples were obtained and macrodissection was performed to enrich the
      tumor cells for DNA extraction when necessary. PCR-based direct DNA sequencing
      was used to investigate the codons 12 and 13 in exon 2 of KRAS gene, exons 11 and
      15 of BRAF gene, exons 9 and 20 of PIK3CA gene and exons 18-21 of EGFR gene.
      RESULTS: Activating mutations were detected in  KRAS (44.1%, 137/311), BRAF
      (5.8%, 9/156), PIK3CA (2.6%, 4/156) and EGFR (1.3%, 2/156) in the study cohort of
      colorectal carcinoma cases. Among KRAS gene mutations, 81.0% (111/137) occurred
      in codon 12, with p.G12D as the most common variant (45.3%, 62/137); 19.0%
      (26/137) occurred in codon 13, with 38G > A (G13D) as the most common variant
      (17.5%, 24/137). CONCLUSIONS: The KRAS mutation frequency is the highest among
      the four genes (KRAS, BRAF, PIK3CA and EGFT) tested in colorectal carcinoma. The
      presence of these gene mutations may provide therapeutic information for targeted
      therapy. Mutation analyses of BRAF and PIK3CA in addition to KRAS should be a
      part of the standard diagnostic algorithm for colorectal carcinoma patients.

PMID- 23157826
TI  - [Correlation between KRAS mutations and clinicopathologic features in colorectal
      carcinomas].
AB  - OBJECTIVE: To investigate mutations of KRAS gene and clinicopathological
      characteristics of colorectal carcinomas (CRC) in Chinese. METHODS: Tumor cells
      were collected by microdissection from paraffin-embedded tumor specimens and
      adjacent normal colon tissues from 167 CRC patients. Genomic DNA was extracted
      and mutations of KRAS gene (codons 12 and 13) were detected by scorpions
      amplification refractory mutation system (Scorpions ARMS). RESULTS: KRAS
      mutations were identified in 66 patients (39.5%), including G13D (21 cases,
      12.6%), G12D (15 cases, 9.0%), G12V (13 cases, 7.8%), G12C (6 cases, 3.6%), G12A
      (5 cases, 3.0%), G12S (4 cases, 2.4%) and G12R (2 cases, 1.2%). Female patients
      had a higher KRAS mutation rate than male (50.0%, 29/58 vs.33.9%, 37/109, P <
      0.05). However, KRAS mutations did not correlate with the patient age, tumor
      sites, histological types and grades (P > 0.05). Additionally, 7 of 18 patients
      with metastatic CRC had KRAS gene mutations. Overall, KRAS gene mutation was
      identified in 59 patients among 149 primary CRC (39.6%). There was no significant
      difference in KRAS mutation between primary and metastatic tumors (P > 0.05).
      CONCLUSIONS: The detection rate of KRAS mutation is higher in female CRC patients
      than the males. The presence of KRAS mutation does not significantly correlate
      with the patients' age, tumor site, differentiation grades and histological
      types. There was no significant difference in KRAS mutation between the primary
      and metastatic tumors.

PMID- 23157827
TI  - [Comparison of real-time PCR-optimized oligonucleotide probe method and Sanger
      sequencing for detection of KRAS mutations in colorectal and lung carcinomas].
AB  - OBJECTIVE: To investigate the feasibility of real-time PCR-optimized
      oligonucleotide probe method for detection of KRAS mutations in lung and
      colorectal carcinomas, as compared with Sanger sequencing method. METHODS:
      Genomic DNA was extracted from formalin fixed paraffin embedded samples of 221
      lung carcinomas and 131 colorectal carcinomas after tumor cell content assessment
      and macrodissection. Real-time PCR-optimized oligonucleotide probe method and
      Sanger sequencing were performed to detect KRAS gene mutations. The frequency of
      KRAS mutation, mutation types, and their concordance were analyzed. RESULTS: KRAS
      mutation was detected in 6.3% (14/221) and 4.5% (10/221) of 221 lung cancer
      samples by using real-time PCR-optimized oligonucleotide probe method and Sanger
      sequencing, respectively, while in 41.2% (54/131) and 40.5% (53/131) of 131
      colorectal cancer samples, respectively. There was no significant correlation
      between KRAS gene mutations and patients' gender and age (P > 0.05). The positive
      rate of KRAS codon 12 mutation was significantly higher than that of KRAS codon
      13 mutation (P < 0.05). The overall concordance between real-time PCR-optimized
      oligonucleotide probe method and Sanger sequencing for KRAS mutation detection
      was 97.4%. CONCLUSION: Real-time PCR-optimized oligonucleotide probe method
      provides an alternative method with high consistency and sensitivity as compared
      to Sanger sequencing in gene mutation detection.

PMID- 23157828
TI  - [Correlation of KRAS gene mutations and clinicopathologic parameters in
      colorectal carcinoma].
AB  - OBJECTIVE: To investigate the relationship between KRAS gene mutations and
      clinicopathological parameters in patients with colorectal carcinoma (CRC).
      METHODS: PCR-based direct sequencing was used to detect the mutations of KRAS
      gene and to correlate between clinicopathological characteristics and the
      presence of various KRAS mutations in 244 cases of CRC. RESULTS: KRAS mutations
      were identified in 92 cases (37.7%) of CRC. Five types of mutation were detected
      at codon 12, including G12D (40 cases, 16.4%), G12V (16 cases, 6.6%), G12A (7
      cases, 2.9%), G12S (5 cases, 2.0%) and G12C (4 cases, 1.6%). Two types of
      mutation were detected at codon 13, including G13D (17 cases, 7.0%) and G13C (2
      cases, 0.8%). One type of mutation was detected in codon 61, i.e. Q61K (1 case,
      0.4%). KRAS mutation rate was higher in females (45.6%, 36/79) than in males
      (32.1%, 53/165; P < 0.05), but not related to another clinicopathological
      characteristics. CONCLUSIONS: Female CRC patients have a higher KRAS mutation
      rate than the male patients. KRAS mutation has no significant correlation with
      patient's age, tumor site, tumor gross appearance, degree of differentiation,
      depth of invasion, TNM stages, lymphatic invasion, abdominal or distant
      metastases and prognosis in this study.

PMID- 23157829
TI  - [Post-transplant lymphoproliferative disorder: a clinicopathologic study of 15
      cases].
AB  - OBJECTIVE: To study the clinical and histopathologic features, diagnosis,
      pathogenesis and therapy of post-transplant lymphoproliferative disorders (PTLD).
      METHODS: The clinical and pathologic features of 15 cases of PTLD were
      retrospectively analyzed by light microscopy, immunohistochemistry and in-situ
      hybridization, according to the updated 2008 WHO classification of tumors of
      hematopoietic and lymphoid tissues. RESULTS: Amongst the 15 cases studied, 14
      cases had received allogenic hematopoietic stem cell transplantation (AHSCT) and
      1 case had received renal transplantation. There were altogether 12 males and 3
      females. The male-to-female ratio was 4:1. The mean age was 30.4 years and the
      median age was 31 years (range from 9 to 60 years). PTLD developed 1.5 to 132
      months after transplantation (median 13.0 months). The mean age of the 14
      patients with AHSCT was 28.3 years (range from 9 to 45 years) and PTLD developed
      1.5 to 19 months after transplantation (mean 4.5 months). Major clinical
      presentation included fever and lymphadenopathy. Twelve cases involved mainly
      lymph nodes and the remaining 3 cases involved tonsils, stomach and small
      intestine, respectively. The histologic types in 4 cases represented early
      lesions, including plasmacytic hyperplasia (n = 1) and infectious mononucleosis
      like PTLD (n = 3). Seven cases were polymorphic PTLD, with 4 cases containing a
      predominance of large cells. Graft-versus-host disease was also seen in the case
      of small intestinal involvement. Four cases were monomorphic PTLD, 3 of which
      were diffuse large B-cell lymphoma, 1 was plasmablastic lymphoma and 1 was a
      mixture of monomorphic and polymorphic PTLD. Foci of necrosis were seen in 5
      cases. The proliferating index of Ki-67 was high. The positive rate of EBV
      encoded RNA in AHSCT was 92.9%. The duration of PTLD onset was shorter in EBV
      positive cases (range from 1.5 to 7 months) than EBV-negative cases (range from
      19 and 132 months). Some cases were treated by reduction of immunosuppression,
      antiviral agents or anti-CD20 monoclonal antibody Rituximab. The duration of
      follow-up in 14 patients ranged from 0 to 8 months. Five of the patients died of
      the disease. CONCLUSIONS: The diagnosis of PTLD relies on morphologic examination
      and immunohistochemistry. Most of them are of B-cell origin. EBV plays an
      important role in the pathogenesis of PTLD. The duration of disease onset is
      shorter in EBV-positive cases. PTLD in AHSCT cases occurs in younger age group,
      with shorter duration of onset, as compared to solid organ transplantation. The
      prognosis of PTLD is poor. The modalities of treatment include reduction of
      immunosuppression, antiviral agents or anti-CD20 monoclonal antibody Rituximab.

PMID- 23157830
TI  - [Clinicopathologic features of micropapillary variant of pure mucinous carcinoma
      of breast].
AB  - OBJECTIVE: To study the clinicopathologic features of pure mucinous carcinomas of
      the breast with diffuse micropapillary pattern. METHODS: Twenty-six cases of
      micropapillary variant of pure mucinous carcinoma of the breast were
      retrospectively reviewed by light microscopy, immunohistochemistry and clinical
      data analyses. RESULTS: The age of 26 female patients ranged from 30 to 77 years
      old, of which 12 cases with clinical details available were mean 54 years old.
      The tumor diameter ranged from 0.8 to 9.0 cm (mean 3.2 cm). Ipsilateral axillary
      nodal metastases were identified in 3 cases. Cutaneous involvement was also found
      in 2 cases. The tumor cells showed the similar architectural arrangement as in
      invasive micropapillary carcinoma, with peripheral borders of the cell clusters
      highlighted by epithelial membrane antigen. Various amount of mucin occupied the
      retraction spaces around the tumor cells. Compared with conventional pure
      mucinous carcinoma of the breast, mucinous carcinomas with micropapillary pattern
      showed different nuclear grades (19 cases of grade I, 2 cases of grade II, 5
      cases of grade III). The micropapillary cell clusters varied in size (22 cases of
      big micropapillary and 4 cases of small). Intraductal carcinoma was observed in
      12 cases. Calcification and psammoma bodies were observed in 8 cases.
      Immunophenotyping, the tumor cells were with higher expression of hormone
      receptors, but HER2 were negative. Ki-67 positive index was 1% ~ 70%.
      Neuroendocrine differentiation was observed in 6 cases. CONCLUSIONS: The
      micropapillary variant of pure mucinous carcinoma of the breast, which mainly
      occurs in younger women, may carry the similar propensity for angioinvasion and
      nodal metastasis as infiltrating micropapillary carcinoma at least in cases with
      high nuclear grade. This morphologic subtype needs to be distinguished from
      conventional pure mucinous carcinoma of the breast and treated properly.

PMID- 23157831
TI  - [Clinical and pathologic analysis of astrocytic tumors with loss of
      heterozygosity on chromosome 10q].
AB  - OBJECTIVE: To study the correlation between loss of heterozygosity (LOH) on
      chromosome 10q and pathologic features, pathogenesis, prognosis of astrocytic
      tumors. METHODS: LOH on 10q was studied by interphase fluorescence in-situ
      hybridization (FISH) in 85 cases of astrocytic tumor, including 35 cases of WHO
      grade II tumors and 50 cases of WHO grade IV tumors. RESULTS: LOH on 10q was
      detected in 6 cases (17.1%) of diffuse astrocytoma (WHO grade II) and 34 cases
      (68.0%) of glioblastoma (WHO grade IV). 10q polysomy was detected in 7 cases
      (20.0%) of diffuse astrocytoma and 11 cases (22.0%) of glioblastoma. The rates of
      LOH on 10q in young age group and elderly group were 36.4% (12/33) and 82.4%
      (28/34), respectively. The difference was of statistical significance (P < 0.05).
      The rates of LOH on 10q in the diffuse astrocytoma and glioblastoma were 21.4%
      (6/28) and 87.2% (34/39), respectively. The difference was also statistically
      significant (P < 0.05). Univariate survival analysis showed that patient age,
      pathologic grade and 10q on LOH correlated with duration of survival (P < 0.05).
      CONCLUSIONS: There are correlation between 10q LOH, patient age and pathologic
      grade of astrocytic tumors. LOH on 10q is also related to the pathogenesis of
      astrocytic tumors and is helpful in predicting prognosis.

PMID- 23157833
TI  - [Effect of fluoride on oxidative stress and Mn-SOD expression in rats with
      endemic fluorosis of coal burning].
AB  - OBJECTIVE: To study the effect of fluoride on the oxidative stress of the rats in
      endemic fluorosis of coal burning and Mn-SOD expression at mRNA and protein
      levels. METHODS: SD rats were divided into 2 groups (the number of female and
      male in each group was the same): control group and fluorosis group. All rats of
      the fluorosis group were fed corn dried by burning coal from endemic fluorosis
      areas with high fluoride content (fluoride 17 mg/kg in feed) to establish an
      animal model of fluorosis. In these rats, dental fluorosis was evaluated. The
      fluoride content in the urine was measured by fluorine ion-elective electrode
      method. The hepatic tissue and serum level of malonaldehyde (MDA) and the
      activities of superoxide dismutase (SOD) and glutathion reductase (GR) were
      measured by biochemical methods. The index signs of liver function were also
      measured from the serum. Reverse transcription-polymerase chain reaction (RT-PCR)
      and Western blot were performed to detect the alterations of Mn-SOD expression in
      the liver at mRNA and protein levels. RESULTS: The dental fluorosis was observed
      in the fluorosis group, and the incidence was 11/11. The fluoride contents [(3.50
      +/- 2.58) mg/L] in the urine of fluorosis rats were increased as compared with
      the control [(1.42 +/- 0.38) mg/L] (P < 0.05). AST [(223.74 +/- 71.51) U/L] and
      total protein [(72.43 +/- 5.59) g/L] of the hepatic function index in fluorosis
      rats showed obviously abnormal as compared with the control [(169.28 +/- 53.74)
      U/L and (82.36 +/- 7.31) g/L], respectively (P < 0.05). In the liver the content
      of MDA [(10.41 +/- 0.59) umol/g protein] increased as compared to the control
      [(5.80 +/- 1.31) umol/g protein, P < 0.01], and the activities of SOD [(62.60 +/-
      8.65) U/mg protein] and GR [ (1.17 +/- 0.66) U/g protein] markedly decreased in
      the fluorosis group compared to the control [SOD (117.28 +/- 8.64) U/mg protein
      and GR [(8.80 +/- 1.59) U/g protein; P < 0.05, P < 0.01]. The level of Mn-SOD in
      the liver was markedly decreased in the fluorosis group [(14.83 +/- 2.50) U/mg
      protein] as compared with the control [(34.05 +/- 5.22) U/mg protein, P < 0.01].
      The levels of mRNA (0.64 +/- 0.15) and protein (0.84 +/- 0.13) of Mn-SOD were
      markedly decreased in the fluorosis group as compared with the control [(0.86 +/-
      0.21) and (1.04 +/- 0.14)], respectively (P < 0.05, P < 0.01). CONCLUSIONS:
      Fluorosis can decrease the activities of Mn-SOD, which is associated with
      decreased levels of mRNA and protein of Mn-SOD. Down-regulation of Mn-SOD
      expression may play an important role in the aggravation of oxidative stress in
      endemic fluorosis.

PMID- 23157832
TI  - [Expression of mRNA and protein of p38, Osx, PI3K and Akt1 in rat bone with
      chronic fluorosis].
AB  - OBJECTIVE: To investigate the expressions of mRNA and protein of p38, Osx, PI3K,
      Akt1 in the rats bone with chronic fluorosis. METHODS: Dental fluorosis were
      observed and the fluoride contents in the urine and bone were detected by fluorin
      ion selective electrode. The morphologic changes and ultrastructure of rats' bone
      were observed by light and electronic microscopy. The expressions of protein and
      mRNA of p38, Osx, PI3K and Akt1 were detected by immunohistochemistry and real
      time PCR, respectively. The contents of BALP and BGP in serum were detected by
      ELISA. RESULTS: The rates of dental fluorosis in the fluorosis rats were
      increased, and the fluoride contents in bone and urine of the fluorosis rats were
      increased compared to the control group, the difference was statistically
      significant (P < 0.05). The bone trabeculae thickness and density and the
      thickness of bone cortex in fluorosis rats were remarkably increased, the space
      of bone trabeculae was reduced, and in accordance with the matching
      morphometrical indices, the difference was statistically significant (P < 0.05)
      as compared with the control rats. The contents of BALP [(54.61 +/- 2.27) U/L]
      and BGP [(2.38 +/- 0.16) ug/L]in the fluoride groups were higher than those in
      the control group, the difference was statistically significant (P < 0.05).
      Ultrastructurally, the broadening of the osseouslacuna was observed. The reduced
      protuberances of the osteocytes, the unclear organelle structure, pyknosis,
      karyotheca increasation and edged chromatin were also observed. Compared to the
      control group, the expressions of protein and its mRNA of p38, Osx, PI3K and Akt1
      were higher in the fluorosis rats than those in the control rats, and the
      difference was statistically significant (P < 0.05). There is no any expression
      of p38, Osx, PI3K and Akt1 in the osteocytes in fluorosis rats. CONCLUSIONS: The
      over-expression of p38, Osx, PI3K and Akt1 in bone tissue of fluorosis rats may
      relate to the accumulation of fluorine in the body. The bone injury mainly occur
      in the stage of the differentiation and proliferation. The upregulation of
      P38MARK signal path and PI3K/Akt1 signal path may be involved in the pathogenesis
      of bone injury caused by fluoride.

PMID- 23157834
TI  - [Malignant mesothelioma of tunica vaginalis of testis: a clinicopathologic
      study].

PMID- 23157835
TI  - [Clinicopathologic study of 20 cases of anaplastic large-cell lymphoma].

PMID- 23157836
TI  - [Consensus for KRAS gene mutation detection in colorectal carcinoma].

PMID- 23157837
TI  - [Technical improvement in dealing with chronic atrophic gastritis samples].

PMID- 23157838
TI  - [Hairy polyp of nasopharynx: report of a case].

PMID- 23157839
TI  - [Primary thymic adenocarcinoma: report of a case].

PMID- 23157840
TI  - [Pathogenesis of giant cell arteritis].

PMID- 23157841
TI  - Role of protein motions in function: comment on "Comparing proteins by their
      internal dynamics: exploring structure-function relationships beyond static
      structural alignments" by Cristian Micheletti.

PMID- 23157842
TI  - Replacement of endoprosthetic implants within a two years follow-up period: a
      statutory health insurance routine data analysis.
AB  - BACKGROUND: The statutory health insurance system embodies a large amount of data
      on the treatments of their members. Depending on joint, prosthesis type, patient
      activity and comorbidity, knee and hip replacements can last up to 20 years.
      Based on statutory health insurance data the main object of this analysis was to
      investigate how high the early revision rate of replacements actually is.
      METHODS: The number of replacements in the years 2005 and 2006 has been extracted
      from the TK database for hip (OPS-Code 5-820, n = 20,875), knee (OPS 5-822, n =
      13,466), upper limbs (OPS 5-824, n = 901), and lower limbs (OPS 5-826)
      replacements. This data has then been related to each consecutive operation (i.
      e. change or excision of joint endoprosthesis) over a joint-specific observation
      period of two years. RESULTS: In 3.7% of the cases joint replacements stood for
      less than 2 years (hip 3.5%, knee 3.8%, upper limbs 6.5%, and lower limbs 5.5%).
      There is a significantly positive correlation between the treatment data of the
      hospitals and the outcome as to low rates of reoperations at early stages. The
      main reason for short lifetime (76 - 81%) is mechanical failure. CONCLUSION: The
      percentage of joint endoprostheses with significantly short lifetimes has been
      unexpectedly high. The de facto lifetimes of joint endoprostheses thus often do
      not match the manufacturers' information. The authors strongly support the idea
      of a national endoprosthesis register as such a register could give detailed
      information on firstly whether these deficits are due to material defects,
      osteolysis or dislocation and secondly which products are mainly affected.

PMID- 23157843
TI  - An experimental study of the interface pressure profile during level walking of a
      new suspension system for lower limb amputees.
AB  - BACKGROUND: Different suspension systems that are used within prosthetic devices
      may alter the distribution of pressure inside the prosthetic socket in lower limb
      amputees. This study aimed to compare the interface pressure of a new magnetic
      suspension system with the pin/lock and Seal-In suspension systems. METHODS:
      Twelve unilateral transtibial amputees participated in the study. The subjects
      walked on a level walkway at a self-selected speed. The resultant peak pressure
      with the three different suspension systems was recorded using F-socket
      transducers. FINDINGS: There were significant statistical differences between the
      three studied suspension systems. Pair-wise analyses revealed that the mean peak
      pressure (kPa) was lower with the magnetic system than it was with the pin/lock
      system over the anterior and posterior aspects during one gait cycle (89.89 vs.
      79.26 and 47.22 vs. 26.01, respectively). Overall, the average peak pressure
      values were higher with the Seal-In system than they were with the new magnetic
      lock and pin/lock system. INTERPRETATION: The new magnetic system might reduce
      the pressure within the prosthetic socket in comparison to the pin/lock and Seal
      In system during one gait cycle. This is particularly important during the swing
      phase of gait and may reduce the pain and discomfort at the distal residual limb
      in comparison to the pin/lock system.

PMID- 23157844
TI  - Functional neuroimages of cortical myoclonus altered by levetiracetam in a
      patient with sialidosis.
AB  - Levetiracetam can suppress sialidosis-related myoclonus but its effects on
      cerebral metabolism warrant elucidation. In this report, fluorodeoxyglucose
      positron emission tomography was conducted before and after levetiracetam in a
      sialidosis patient. By subtracting the drug "off" from "on" signals, regions of
      enhanced metabolism were shown to be allocated mostly in the bilateral fronto
      temporal regions whereas regions of reduced metabolism were distributed mainly in
      the occipital areas. Imaging changes suggest that the effects of levetiracetam
      may be different in different brain regions. The drug may also elicit fronto
      temporal inhibitory impulses to suppress the vigorous myoclonus in sialidosis.

PMID- 23157845
TI  - Possible induction of acute disseminated encephalomyelitis (ADEM)-like
      demyelinating illness by intrathecal mesenchymal stem cell injection.
AB  - We report a 27-year-old woman with an episode of encephalitis and optic neuritis,
      followed by autologous bone marrow mesenchymal stem cell transplants and possible
      induction of acute disseminated encephalomyelitis-like demyelinating illness.

PMID- 23157846
TI  - Is progressive upper-body apraxia a corticobasal syndrome?
AB  - Corticobasal degeneration (CBD) is characterized by various clinical
      manifestations including corticobasal syndrome, progressive supranuclear palsy
      like syndrome and frontotemporal dementia. Focal cortical atrophy syndrome as the
      initial manifestation rarely occurs in CBD. Here, we present a 62-year-old man
      and a 70-year-old man who were admitted due to clumsiness in the arms. On initial
      neurological examination, they showed asymmetric limb apraxia without
      parkinsonism or global cognitive dysfunction. Brain MRI showed focal atrophy in
      the frontal and prefrontal cortices, and brain positron emission tomography scan
      revealed decreased metabolism in these same brain locations. Although these
      patients developed parkinsonism and dystonia within several years, the
      neurological signs were limited to the arms for a long period. "Progressive upper
      body apraxia" may be a rare clinical manifestation of CBD which shows a benign
      clinical outcome. The patients described may enhance our understanding of the
      clinical heterogeneity of this disease.

PMID- 23157847
TI  - [Preeclampsia and benefit form magnesium sulfate. About 105 cases].
AB  - OBJECTIVES: The aim of this study was to determine the amount of magnesium
      sulfate involved when we diagnose a severe preeclampsia in pregnant women. Other
      goals were to know what the MgSO4 side-effects and complications are, and what
      benefits this treatment brings to prevent an eclampsia. PATIENTS AND METHODS:
      This retrospective and descriptive study was conducted for 7 years. We identified
      105 women treated by MgSO4 out of 560 preeclampsia cases. To prevent eclampsia,
      those women were administrated MgSO4 before, during or after labor. All data
      about hospitalization term and MgSO4 term administration were collected in order
      to understand if MgSO4 side-effects for the women and the fetus occurred before,
      during or after labor. Those tables are compared with the MgSO4 administered
      dosages. RESULTS: MgSO4 isn't systematically used in all the preeclampsia cases.
      Forty percent of women under treatment presented low side effects. Overdoses,
      encountered in 31.4% of cases, regressed as soon as the MgSO4's perfusion was
      stopped. No major complications were noted. Only 0.95% of women treated by MgSO4
      presented an eclampsia. DISCUSSION AND CONCLUSION: MgSO4 administered only to
      women having a neurological preeclampsia, within therapeutic doses and with
      rigorous monitoring, does not bring deleterious effects to the mother or newborn
      baby. Consequently, MgSO4's benefits were above the risks.

PMID- 23157848
TI  - 6th Golden Helix Pharmacogenomics Day: pharmacogenomics and individualized
      therapy.
AB  - The Golden Helix Pharmacogenomics Days are international scientific meetings
      aiming to educate healthcare professionals and biomedical scientists about
      pharmacogenomics and personalized medicine. In this meeting report, we provide an
      overview of the scientific lectures and the topics discussed during the 6th
      Golden Helix Pharmacogenomics Day that was held in Belgrade, Serbia last June 5,
      2012. The scientific program included lectures by the local and international
      speakers from Europe and the United States.

PMID- 23157849
TI  - Mini-implants in the palatal slope--a retrospective analysis of implant survival
      and tissue reaction.
AB  - BACKGROUND: To identify insertion procedure and force application related
      complications in Jet Screw (JS) type mini-implants when inserted in the palatal
      slope. METHODS:  SETTING AND SAMPLE POPULATION: The Department of Orthodontics,
      the University Hospital Munster. Forty-one consecutively started patients treated
      using mini-implants in the palatal slope. In this retrospective study, 66 JS were
      evaluated. Patient records were used to obtain data on the mode of utilization
      and complications. Standardized photographs overlayed with a virtual grid served
      to test the hypothesis that deviations from the recommended insertion site or the
      type of mechanics applied might be related to complications regarding bleeding,
      gingival overgrowth or implant failure. RESULTS: Two implants (3%) were lost, and
      two implants (3%), both loaded with a laterally directed force, exhibited
      loosening while still serving for anchorage. Complications that required
      treatment did not occur, the most severe problem observed being gingival
      proliferation which was attributable neither to patients' age nor to applied
      mechanics or deviations from the ideal implant position. CONCLUSIONS: The JS mini
      implant is reliable for sagittal and vertical movements or anchorage purposes.
      Laterally directed forces might be unfavorable. The selection of implant length
      as well as the insertion procedure should account for the possibility of gingival
      overgrowth.

PMID- 23157850
TI  - SRY mutation analysis by next generation (deep) sequencing in a cohort of
      chromosomal Disorders of Sex Development (DSD) patients with a mosaic karyotype.
AB  - BACKGROUND: The presence of the Y-chromosome or Y chromosome-derived material is
      seen in 4-60% of Turner syndrome patients (Chromosomal Disorders of Sex
      Development (DSD)). DSD patients with specific Y-chromosomal material in their
      karyotype, the GonadoBlastoma on the Y-chromosome (GBY) region, have an increased
      risk of developing type II germ cell tumors/cancer (GCC), most likely related to
      TSPY. The Sex determining Region on the Y gene (SRY) is located on the short arm
      of the Y-chromosome and is the crucial switch that initiates testis determination
      and subsequent male development. Mutations in this gene are responsible for sex
      reversal in approximately 10-15% of 46,XY pure gonadal dysgenesis (46,XY DSD)
      cases. The majority of the mutations described are located in the central HMG
      domain, which is involved in the binding and bending of the DNA and harbors two
      nuclear localization signals. SRY mutations have also been found in a small
      number of patients with a 45,X/46,XY karyotype and might play a role in the
      maldevelopment of the gonads. METHODS: To thoroughly investigate the presence of
      possible SRY gene mutations in mosaic DSD patients, we performed next generation
      (deep) sequencing on the genomic DNA of fourteen independent patients (twelve
      45,X/46,XY, one 45,X/46,XX/46,XY, and one 46,XX/46,XY). RESULTS AND CONCLUSIONS:
      The results demonstrate that aberrations in SRY are rare in mosaic DSD patients
      and therefore do not play a significant role in the etiology of the disease.

PMID- 23157851
TI  - From the city to the bush: increases in patient co-payments for medicines have
      impacted on medicine use across Australia.
AB  - AIM: To determine whether the national declines in prescription medicine use
      occurring after the 2005 21% increase in co-payments affected all areas of
      Australia or were specific to remote and disadvantaged areas. METHODS: Observed
      dispensing of proton pump inhibitors (PPIs) and statins were obtained for 1392
      statistical local areas (SLA) of Australia in 2004 and 2006. Expected dispensing
      was based on national dispensing rates and was age standardised to each SLA.
      Expected dispensing for 2006 was based on pre-2005 prescription trends. Ratios of
      observed to expected dispensing (dispensing ratios) for each SLA were calculated.
      Mean dispensing ratios for each medicine and year were calculated for all
      remoteness and disadvantage groups. Generalised regression models compared the
      percentage change in dispensing ratios from 2004 to 2006. RESULTS: Between 2004
      and 2006 PPI dispensing fell significantly in major cities (-13.7%, 95% CI=-17.3-
      9.8), inner regional (-14.0, 95%CI=-19.5--8.2), outer regional (-14.6%, 95%CI=
      19.9--9.0) and remote areas (-9.4%, 95%CI=-16.4--1.8). Statin dispensing fell in
      all groups but the most remote (range 6-7%). When focussing on disadvantage, PPI
      dispensing fell significantly in all groups (range 12-15%). Statins dispensing
      did not fall significantly in the most disadvantaged areas (-2.9%, 95%CI=-8.6
      3.2) but did in the least (-6.5%, -11.3--1.5) and second-least (-5.8, -10.5--0.9)
      disadvantaged areas. Dispensing of PPIs and statins in the most remote and
      disadvantaged areas remained substantially below levels expected for Australia
      after the 21% co-payments increase. CONCLUSIONS: The findings suggest that the
      2005 21% in patient co-payments adversely affected prescription medicine use in
      all areas of Australia and was not specific to remote or disadvantaged areas.
      Indeed, dispensing of statins fell significantly in all but the most remote and
      disadvantaged areas, and the existing gap in dispensing of PPIs and statins was
      not widened by the co-payments increase. PPIs, which are used at above-prevalence
      rates in Australia and have cheaper over-the-counter substitutes available, were
      more sensitive to co-payment increases than were statins.

PMID- 23157852
TI  - BMI can influence adult males' and females' airway hyperresponsiveness
      differently.
AB  - BACKGROUND: Epidemiological data indicate that obesity is a risk factor for
      asthma, but scientific literature is still debating the association between
      changes in body mass index (BMI) and airway hyperresponsiveness (AHR). METHODS:
      This study aimed at evaluating the influence of BMI on AHR, in outpatients with
      symptoms suggestive of asthma.4,217 consecutive adult subjects (2,439 M; mean
      age: 38.2+/-14.9 yrs; median FEV1 % predicted: 100 [IQR:91.88-107.97] and
      FEV1/FVC % predicted: 85.77% [IQR:81.1-90.05]), performed a methacholine
      challenge test for suspected asthma. Subjects with PD20 < 200 or 200 < PD20 < 800
      or PD20 > 800 were considered affected by severe, moderate or mild AHR,
      respectively. RESULTS: A total of 2,520 subjects (60% of all cases) had a PD20 <
      3,200 MUg, with a median PD20 of 366 MUg [IQR:168-1010.5]; 759, 997 and 764
      patients were affected by mild, moderate and severe AHR, respectively. BMI was
      not associated with increasing AHR in males. On the contrary, obese females were
      at risk for AHR only when those with moderate AHR were considered (OR: 1.772
      [1.250-2.512], p = 0.001). A significant reduction of FEV1/FVC for unit of BMI
      increase was found in moderate AHR, both in males (beta = -0.255; p =0.023) and
      in females (beta = -0.451; p =0.017). CONCLUSIONS: Our findings indicate that
      obesity influences AHR only in females with a moderate AHR level. This influence
      may be mediated by obesity-associated changes in baseline lung function.

PMID- 23157853
TI  - The impact of semantic dementia on everyday actions: evidence from an ecological
      study.
AB  - In theory, semantic memory may trigger and support the execution of everyday
      activities. This study explored this question by comparing three patients with
      semantic dementia to 40 normal controls performing different everyday activities.
      Participants were tested in their home using the Instrumental Activities of Daily
      Living Profile, an ecological measure of everyday functioning. Participants were
      informed that they had unknowingly invited two guests for lunch and should
      prepare accordingly. With these instructions, they dress to go outdoors, go to
      the grocery store, shop for food, prepare a hot meal, have the meal with the
      guests, and clean up after the meal. Performance was analyzed on the basis of
      four operations related to problem solving: formulate a goal, plan, execute, and
      verify attainment of the goal. Results indicate that compared to normal controls,
      two patients had significant difficulties and needed assistance with all
      operations of problem-solving, particularly while preparing a meal and cleaning
      up after the meal. One patient showed no difficulties despite severe semantic
      deficits. These results suggest that semantic deficits alone cannot explain the
      difficulties observed, but may contribute to some aspects of everyday actions
      such as those involved in everyday problem-solving.

PMID- 23157854
TI  - Pharmaceutical information systems and possible implementations of informed
      consent -- developing an heuristic.
AB  - BACKGROUND: Denmark has implemented a comprehensive, nationwide pharmaceutical
      information system, and this system has been evaluated by the Danish Council of
      Ethics. The system can be seen as an exemplar of a comprehensive health
      information system for clinical use. ANALYSIS: The paper analyses 1) how informed
      consent can be implemented in the system and how different implementations create
      different impacts on autonomy and control of information, and 2) arguments
      directed towards justifying not seeking informed consent in this context. RESULTS
      AND CONCLUSION: Based on the analysis a heuristic is provided which enables a
      ranking and estimation of the impact on autonomy and control of information of
      different options for consent to entry of data into the system and use of data
      from the system.The danger of routinisation of consent is identified.The Danish
      pharmaceutical information system raises issues in relation to autonomy and
      control of information, issues that will also occur in relation to other similar
      comprehensive health information systems. Some of these issues are well
      understood and their impact can be judged using the heuristic which is provided.
      More research is, however needed in relation to routinisation of consent.

PMID- 23157857
TI  - [Research and development of rapid detection technologies and serial equipment
      for drinking water and food].

PMID- 23157856
TI  - Comparing the odds of postpartum haemorrhage in planned home birth against
      planned hospital birth: results of an observational study of over 500,000
      maternities in the UK.
AB  - BACKGROUND: The aim of this study is to compare the odds of postpartum
      haemorrhage among women who opt for home birth against the odds of postpartum
      haemorrhage for those who plan a hospital birth. It is an observational study
      involving secondary analysis of maternity records, using binary logistic
      regression modelling. The data relate to pregnancies that received maternity care
      from one of fifteen hospitals in the former North West Thames Regional Health
      Authority Area in England, and which resulted in a live or stillbirth in the
      years 1988-2000 inclusive, excluding 'high-risk' pregnancies, unplanned home
      births, pre-term births, elective Caesareans and medical inductions. RESULTS:
      Even after adjustment for known confounders such as parity, the odds of
      postpartum haemorrhage (>=1000ml of blood lost) are significantly higher if a
      hospital birth is intended than if a home birth is intended (odds ratio 2.5, 95%
      confidence interval 1.7 to 3.8). The 'home birth' group included women who were
      transferred to hospital during labour or shortly after birth. CONCLUSIONS: Women
      and their partners should be advised that the risk of PPH is higher among births
      planned to take place in hospital compared to births planned to take place at
      home, but that further research is needed to understand (a) whether the same
      pattern applies to the more life-threatening categories of PPH, and (b) why
      hospital birth is associated with increased odds of PPH. If it is due to the way
      in which labour is managed in hospital, changes should be made to practices which
      compromise the safety of labouring women.

PMID- 23157858
TI  - [Distribution of chromium in whole blood and urine among general population in
      China between year 2009 and 2010].
AB  - OBJECTIVE: To evaluate the chromium (Cr) levels in blood and urine among general
      population in China between 2009 and 2010, and thereby to analyze its prevalent
      features. METHODS: From year 2009 to 2010, a total of 11 983 subjects of general
      population aged between 6 and 60 year-old were recruited from 24 districts in 8
      provinces in eastern, central and western China mainland, by cluster random
      sampling method. The information about their living environment and health status
      were collected by questionnaire, and 11 983 blood samples and 11 853 urine
      samples were also collected. Inductively coupled plasma mass spectrometry (ICP
      MS) was applied to test the Cr level both in blood and urine; and the Cr
      distribution in blood and urine among groups of population in different ages,
      genders and districts, were then analyzed. RESULTS: Among general population in
      China, the geometric mean (GM) of Cr concentration in blood was 1.19 ug/L, with
      median at 1.74 ug /L and 95% percentile at 5.59 ug/L. The Cr concentration in
      blood among males and females were separately 1.18 ug/L and 1.20 ug/L(P > 0.05);
      while its GM in the groups of population aged 6 - 12, 12 - 16, 16 - 20, 20 - 30,
      30 - 45 and 45 - 60 years old were 1.00, 1.22, 1.01, 1.40, 1.27 and 1.30 ug/L (P
      < 0.01), respectively; and the figures in populations from eastern, central and
      western China were 1.00, 1.70 and 1.98 ug/L (P < 0.01), respectively. Among
      general population, the GM of Cr concentration in urine was 0.53 ug/L, with
      median was lower than 0.42 ug/L and 95% percentile at 3.53 ug/L. The Cr
      concentration in urine among males and females were separately 0.52 ug/L and 0.53
      ug/L (P > 0.05);while its GM in the groups of population aged 6 - 12, 12 - 16, 16
      - 20, 20 - 30, 30 - 45 and 45 - 60 years old were 0.56, 0.60, 0.52, 0.50, 0.52
      and 0.46 ug/L (P < 0.01), respectively;and the figures in populations from
      eastern, central and western China were 0.58, < 0.42 and 0.60 ug/L (P < 0.01),
      respectively. CONCLUSION: The study reported the Cr levels in blood and urine
      among general population in China, and thereby provided basic data evidence for
      the following Cr biological monitoring studies in near future.

PMID- 23157859
TI  - [Prevalence and characteristic of overweight and obesity among adults in China,
      2010].
AB  - OBJECTIVE: To study the prevalence and characteristics of overweight and obesity
      among Chinese adults aged 18 and above, in year 2010. METHODS: A total of 98 271
      adults aged 18 and above, who were sampled from 162 surveillance points of 31
      provinces of China mainland, were enrolled in the study. Weight and height of
      each subject were measured, and then body mass index (BMI) was calculated.
      Overweight was defined as 24 kg/m2 <= BMI < 28 kg/m2, while obesity was defined
      as BMI >= 28 kg/m2. After complex weighting, the prevalence of overweight and
      obesity among total population and specified rates among different populations by
      gender and districts and age were calculated. RESULTS: Prevalence rate of
      overweight among Chinese adults was 30.6%, separately at 31.5% and 29.7% among
      males and females (chi2 = 16.05, P < 0.01); 27.1%, 37.2% and 32.3% in groups of
      population aged 18 - 44, 45 - 59 and over 60 year-old, respectively (chi2 =
      482.00, P < 0.01); separately at 33.9% and 29.1% in urban and rural areas (chi2 =
      21.14, P < 0.01); 32.0%, 31.1% and 28.0% in eastern, central and western regions,
      respectively (chi2 = 8.72, P < 0.05). Prevalence rate of obesity among Chinese
      adults was 12.0%, separately at 11.9% and 12.1% among males and females (chi2 =
      0.33, P > 0.05); and 10.6%, 14.7% and 12.6% in groups of populations aged 18 -
      44, 45 - 59 and over 60 year-old, respectively (chi2 = 111.25, P < 0.01);
      separately at 14.2% and 11.0% in urban and rural areas (chi2 = 12.11, P < 0.01);
      and 13.5%, 11.9% and 9.9% in eastern, central and western regions, respectively
      (chi2 = 10.05, P < 0.01). The total prevalence rate of overweight and obesity
      among Chinese adults was 42.6%. It appeared that the total prevalence rate of
      overweight and obesity among urban populations (48.1%) were higher than rural
      populations (40.1%) (chi2 = 20.37, P < 0.01); while the total rate showed a
      gradual decreasing trend from eastern (45.5%) to central (43.0%) and western
      (37.9%) regions (chi 2= 10.46, P < 0.01). CONCLUSION: The prevalence of
      overweight and obesity were comparatively high among Chinese adults aged 18 and
      above in year 2010, and significant differences could be found among gender, age,
      urban or rural areas and eastern, central or western districts.

PMID- 23157861
TI  - [Survey of dietary intake of Chinese adults in 2010].
AB  - OBJECTIVE: To analyze the status of dietary intake of Chinese adults in 2010.
      METHODS: In 2010, China Chronic Disease Surveillance was carried out in 31
      provinces and Xinjiang Production and Construction Corps. The survey was
      undertaken in 162 surveillance sites in the national disease surveillance points
      system by stratified multi-stage cluster random sampling. The participants were
      local residents (living in the area for more than 6 months) aged 18 years and
      above in the surveillance sites. A semi-quantitative food frequency questionnaire
      was used to measure the dietary intake for 97 187 urban and rural adults aged 18
      years and above. After complex weighting for the sample, the average daily
      consumption for major food was analyzed for different genders and regions.
      RESULTS: After complex weighting, the median of cereal, rice and wheat flour
      intake for Chinese adults was 375.0 g. The median of livestock meat intake was
      57.1 g with western areas (85.7 g) much higher than eastern (57.1 g) and central
      areas (46.2 g) (chi2 = 2054.82, P < 0.01). The median of poultry intake was 7.1
      g, eastern areas (10.0 g) higher than western and central areas (both 6.7 g)
      (chi2 = 1210.86, P < 0.01). The median of seafood intake was 14.3 g, eastern
      (15.0 g) much higher than central (14.3 g) and western areas (7.1 g) (chi2 =
      5603.37, P < 0.01). The median of daily intake for eggs was 21.4 g, western (14.3
      g) lower than eastern and central areas (both 21.4 g) (chi2 = 1699.11, P < 0.01).
      The median of dairy product intake was 42.9 g, eastern (57.1 g) higher than
      western and central areas (both 35.7 g) (chi2 = 196.35, P < 0.01). Overall, 52.8%
      of urban and rural residents did not meet recommended amount of fruit and
      vegetable intake. The rate of inadequate intake of fruit and vegetable was higher
      in rural (55.7%) than urban areas (46.1%, chi2 = 929.43, P < 0.01). CONCLUSION:
      The adult intake of cereal category foods tended to decline in 2010, and the
      intakes of vegetable and fruits, fishery products as well as dairy products were
      evidently deficient and regionally varied.

PMID- 23157860
TI  - [Awareness rate, treatment rate and control rate of dyslipidemia in Chinese
      adults, 2010].
AB  - OBJECTIVE: To explore the awareness, treatment and control rates of dyslipidemia
      among Chinese adults aged over 18 in 2010, and to analyze the prevalent features.
      METHODS: 97 409 subjects aged over 18 were recruited from 162 monitoring sites
      around 31 provinces in China mainland in 2010, applying multi-stage stratified
      cluster random sampling method. Information about subjects' history of
      dyslipidemia, treatment and control were collected by face-to-face interview; and
      each subject's fasting venous blood was drawn in the morning before having food,
      to test total cholesterol (TC), triglyceride (TG), high density lipoprotein
      cholesterol (HDL-C) and low density lipoprotein-cholesterol (LDL-C). In total, 51
      818 cases of dyslipidemia ever or now, including 2235 subjects who once suffered
      from dyslipidemia but had their blood lipid controlled to normal, were screened
      out. And the awareness, treatment and control rates were calculated by complex
      weighting. RESULTS: The awareness rate of dyslipidemia among Chinese adults was
      10.93%, while the stratified rates were 6.00%, 16.75% and 18.74% in the groups of
      subjects aged 18 - 44, 45 - 59 and over 60 years old, respectively (chi2 =
      1293.02, P < 0.01); 10.32% and 11.71% among males and females, respectively (chi2
      = 18.67, P < 0.01); 16.59% and 8.17% in groups from urban and rural areas,
      respectively (chi2 = 618.38, P < 0.01); and 12.22%, 11.75% and 8.26% in groups
      from eastern, central and western China, respectively (chi2 = 117.04, P < 0.01).
      The treatment rate of dyslipidemia was 6.84% among Chinese adults, while the
      stratified rates were 3.55%, 10.73% and 12.05% in the groups of subjects aged 18 
      44, 45 - 59 and over 60 years old, respectively (chi2 = 858.72, P < 0.01); 6.37%
      and 7.43% among males and females, respectively (chi2 = 16.69, P < 0.01); 10.17%
      and 5.21% in groups from urban and rural areas, respectively (chi2 = 327.51, P <
      0.01); and 7.33%, 7.52% and 5.41% in groups from eastern, central and western
      China, respectively (chi2 = 50.71, P < 0.01). The control rate of dyslipidemia
      was 3.53% among total subjects, while whose stratified rates were 1.64%, 5.49%
      and 6.94% in the groups of subjects aged 18 - 44, 45 - 59 and over 60 years old,
      respectively (chi2 = 554.12, P < 0.01); 2.57% and 4.75% among males and females,
      respectively (chi2 = 131.04, P < 0.01); 5.23% and 2.70% in groups from urban and
      rural areas, respectively (chi2 = 165.13, P < 0.01) ; and 4.21%, 3.89% and 2.17%
      in groups from eastern, central and western China, respectively (chi2 = 91.45, P
      < 0.01). CONCLUSION: The awareness, treatment and control rates of dyslipidemia
      have been comparatively low among Chinese adults, especially among the population
      who were young, or who were from rural area or western China.

PMID- 23157855
TI  - Vaginal progesterone vs. cervical cerclage for the prevention of preterm birth in
      women with a sonographic short cervix, previous preterm birth, and singleton
      gestation: a systematic review and indirect comparison metaanalysis.
AB  - OBJECTIVE: No randomized controlled trial has compared vaginal progesterone and
      cervical cerclage directly for the prevention of preterm birth in women with a
      sonographic short cervix in the mid trimester, singleton gestation, and previous
      spontaneous preterm birth. We performed an indirect comparison of vaginal
      progesterone vs cerclage using placebo/no cerclage as the common comparator.
      STUDY DESIGN: Adjusted indirect metaanalysis of randomized controlled trials.
      RESULTS: Four studies that evaluated vaginal progesterone vs placebo (158
      patients) and 5 studies that evaluated cerclage vs no cerclage (504 patients)
      were included. Both interventions were associated with a statistically
      significant reduction in the risk of preterm birth at <32 weeks of gestation and
      composite perinatal morbidity and mortality compared with placebo/no cerclage.
      Adjusted indirect metaanalyses did not show statistically significant differences
      between vaginal progesterone and cerclage in the reduction of preterm birth or
      adverse perinatal outcomes. CONCLUSION: Based on state-of-the-art methods for
      indirect comparisons, either vaginal progesterone or cerclage are equally
      efficacious in the prevention of preterm birth in women with a sonographic short
      cervix in the mid trimester, singleton gestation, and previous preterm birth.
      Selection of the optimal treatment needs to consider adverse events, cost and
      patient/clinician preferences.

PMID- 23157862
TI  - [Type 2 diabetes prevalence and its risk factors among migrants and nonmigrants
      aged 35 years and older in Three Gorge Dam area, China].
AB  - OBJECTIVE: To explore type 2 diabetes prevalence and its risk factors among
      migrants and nonmigrants aged 35 years and older in Three Gorge Dam area in
      Yichang City of Hubei province, China. METHODS: A sample of 9865 rural residents
      (including 1949 Three Gorge Dam migrants and 7916 nonmigrants) aged 35 years old
      and over was selected from September to December in 2007 by the method of multi
      stage cluster random sampling in Yiling district, Yichang City of Hubei province.
      The study subjects were assessed by interview, examination, and blood samples.
      Information on demographics, migrant information, lifestyle, history of diabetes
      and hypertension was obtained by a questionnaire interview. An overnight fasting
      blood specimen was collected to measure serum glucose, total cholesterol,
      triglyceride, high-density lipoprotein cholesterol (HDL-C) and low density
      lipoprotein-cholesterol (LDL-C). Height, weight, waist circumference, hip
      circumference and blood pressure were measured. Oral glucose tolerance test
      (OGTT) was carried out for those whose fasting glucose was equal to or exceeded
      6.1 mmol/L. The standardized prevalence of type 2 diabetes was calculated based
      on national census in the year of 2000. Multiple logistic regression analysis was
      used to explore the potential risk factors of type 2 diabetes. RESULTS: The crude
      prevalence of type 2 diabetes among nonmigrants was 3.93% (310/7885) (male: 3.90%
      (129/3304), female: 3.95% (181/4581)), and that of migrants was 6.55% (127/1939)
      (male: 6.85% (52/759), female: 6.36% (75/1180)). The crude prevalence of type 2
      diabetes among migrants was higher than that of nonmigrants (chi2 = 25.10, P <
      0.01 (male: chi2 = 12.59, P < 0.01; female: chi2 = 12.78, P < 0.01)). The
      prevalence of type 2 diabetes among nonmigrants was 3.87% in males and 4.15% in
      females. The standardized prevalence of type 2 diabetes among migrants was 6.92%
      in males and 6.33% in females. Logistic regression analysis showed that age
      (taking 35 - 44 years old as reference, 45 - 54 years old: OR = 1.45, 95%CI: 1.07
      - 1.95; 55 - 64 years old: OR = 2.08, 95%CI: 1.53 - 2.84; 65 years old and over:
      OR = 1.85, 95%CI: 1.25 - 2.75), family history of diabetes (OR = 2.83, 95%CI:
      1.70 - 4.72), overweight or obesity (overweight: OR = 1.36, 95%CI: 1.05 - 1.78;
      obesity: OR = 2.11, 95%CI: 1.47 - 3.01), central obesity (OR = 1.84, 95%CI: 1.39 
      2.44), abnormal triglyceride (OR = 1.54, 95%CI: 1.21 - 1.97), abnormal total
      cholesterol (OR = 1.40, 95%CI: 1.11 - 1.77) and abnormal LDL-C (OR = 1.82, 95%CI:
      1.19 - 2.79) increased the risk of type 2 diabetes, and regular physical activity
      (OR = 0.57, 95%CI: 0.45 - 0.72) was the protective factor of type 2 diabetes.
      CONCLUSION: The prevalence of type 2 diabetes among Three Gorge Dam migrants was
      higher than that of nonmigrants. Increasing age, regular physical activity,
      family history of diabetes, overweight or obesity, central obesity, abnormal
      triglyceride, abnormal total cholesterol and abnormal LDL-C were related to type
      2 diabetes.

PMID- 23157863
TI  - [Analysis and prediction of breast cancer incidence trend in China].
AB  - OBJECTIVE: Based on the registered female breast cancer data from 1998 to 2007,
      to analyze the incidence of female breast cancer during the period and then to
      predict its trend from 2008 to 2015. METHODS: The incidence data of breast cancer
      from 1998 to 2007 were sorted from National Cancer Registry Database, including
      74 936 cases from urban areas and 8230 cases from rural areas, separately
      covering 164 830 893 and 55 395 229 person years. The crude incidence rates in
      urban and rural areas were calculated, and the age-standardized rate (ASR) was
      adjusted by World Segi's population composition. JoinPoint software was applied
      to analyze the 10 years' incidence trend and calculated the annual percentage of
      changing (APC), while Age-Period-Cohort Bayesian Model was used to fit the data
      and predict the incidence of breast cancer between 2008 and 2015. RESULTS: From
      1998 to 2007, the incidence of breast cancer in the urban cancer registration
      areas was 45.46/100 000 (74 936/164 830 893), whose ASR was 31.28/100 000. While
      in rural registration areas, the incidence and ASR was 14.86/100 000 (8230/55 395
      229) and 12.13/100 000. The breast cancer incidence in urban and rural areas
      separately rose from 36.17/100 000 (3920/10 838 355) and 10.39/100 000 (436/4 197
      806) in 1998 to 51.24/100 000 (11 302/22 057 787) and 19.61/100 000 (1475/7 522
      690) in 2007. During the 10 years, the breast cancer incidence increased both in
      urban and rural areas, but the increase rate in rural incidence (6.3%) was more
      significant than it in urban areas (3.9%). Age-Period-Cohort Bayesian Model
      predicted that the breast cancer incidence would increase to 53.87/100 000 (185
      585 new cases) in urban areas and 40.14/100 000 (132 432 new cases) in rural
      areas, respectively. CONCLUSION: The breast cancer incidence has been increasing
      annually both in urban and rural areas in China; and an annually increase number
      of new cases have been predicted.

PMID- 23157864
TI  - [Assessment of the posttraumatic symptoms among survivors for three years
      following Wenchuan Earthquake].
AB  - OBJECTIVE: To investigate the incidence of posttraumatic stress disorder (PTSD)
      and its influencing factors for three years following the "5.12" Wenchuan
      Earthquake. METHODS: A systematic sampling of 870 subjects who came from Beichuan
      (605 persons) and Jiangyou (265 persons) areas were investigated by adopting
      subscale of PTSD Checklist-Civilian Version (PCL-C) and Social Demographic
      Questionnaire. RESULTS: The incidence rate of PTSD was 8.5% (74/870), the
      incidence rates of PTSD for the area of Beichuan and Jiangyou were 11.2% (68/605)
      and 2.3% (6/265) respectively. Subjects from Beichuan had higher PTSD incidence
      rate compared to Jiangyou (P < 0.05). The prevalence of PTSD for female and male
      were 11.8% (55/465) and 4.7% (19/405) respectively, female had higher prevalence
      of PTSD compared to male (P < 0.05). The incidence rates of PTSD for victims who
      suffered from major property lost and those who lost less were 13.3% (62/466) and
      3.0% (12/404) respectively, victims suffered major property lost had higher
      incidence rate of PTSD(P < 0.05). The incidence rates of PTSD for victims who
      lost family members and those did not were 13.4% (45/336) and 5.4% (29/534)
      respectively, victims who lost family members had higher incidence rates of PTSD
      (P < 0.05). The posttraumatic symptoms for survivors who suffered from PTSD
      mainly focused on the symptoms of reexpericement and over vigilance, the
      prevalence rate was 100% (74/74). Exaggerated startle response, intense
      psychological distress and physiological reactivity were higher than others in
      total 17 symptoms, accounting for 96% (71/74), 94% (70/74) and 90% (67/74). The
      logistic regression showed that being female, victims who suffered from major
      property lost, lost family member in this earthquake were the risk factors of
      PTSD, and the values of OR (95%CI) were 2.746 (1.580 - 4.772), 3.616 (1.871 -
      6.988) and 1.805(1.057 - 3.084), respectively. CONCLUSION: Posttraumatic symptoms
      were still common among survivors three years after "5.12" Wenchuan Earthquake.
      Survivors in Beichuan (heavy hit area), female victims, victims who suffered from
      major property lost, victims who lost family member need more social and economic
      support.

PMID- 23157865
TI  - [The association of sleep hygiene and sleep quality among school-age children].
AB  - OBJECTIVE: To study the association between sleep hygiene and sleep duration and
      quality among school-age children, and to explore the risk factors related to
      poor sleep hygiene. METHODS: Totally 2019 grade-five children were sampled by
      stratified cluster random sampling from 10 primary schools in Shanghai, during
      November and December 2009. Questionnaires were used to investigate children and
      their parents. Adolescent Sleep Hygiene Scale (ASHS) was used to inquiry sleep
      hygiene of children; Children Sleep Habits Questionnaire (CSHQ) was used to
      assess their sleep duration and quality; Family and Social Environment
      Questionnaire was used to collect demographic and socio-economic information. T
      test, one-way ANOVA and multiple linear regression model were established to
      identify the risk factors for sleep hygiene. RESULTS: The age of subjects was
      (10.81 +/- 0.38) years old, 49.0% (989/2019) were boys. The ASHS total score was
      125.43 +/- 15.17, girls with better sleep hygiene than boys (127.05 +/- 14.41 vs
      123.74 +/- 15.75, P < 0.05). The sleep duration was (9.47 +/- 0.58)h/d, children
      slept less than 9 h/d had lower ASHS total score than those slept 9 - 10 h/d or
      over 10 h/d (121.69 +/- 16.09 vs 126.17 +/- 14.62 vs 126.50 +/- 15.36, P < 0.05).
      Children with poor sleep quality had worse sleep hygiene than those with good
      sleep quality (121.00 +/- 15.84 vs 128.36 +/- 13.92, P < 0.05). Children with
      television set in bedroom had lower ASHS total score than the others (122.40 +/-
      15.76 vs 126.74 +/- 14.66, P < 0.05). Children from single parent family had
      lower ASHS total score (117.90 +/- 16.80 vs 125.94 +/- 14.89, P < 0.05). Children
      whose father had irregular sleep or wake pattern had lower ASHS total score
      (122.65 +/- 15.30 vs 125.89 +/- 14.90 vs 127.79 +/- 14.71, P < 0.05). The
      regression model confirmed that existence of television set in children's
      bedroom, single-parent family and father's irregular sleep pattern were the risk
      factors of poor sleep hygiene. CONCLUSION: Sleep hygiene was closely associated
      with sleep duration and quality among school-age children. Children with
      television set in bedroom, male, from single parent family and whose father had
      irregular sleep or wake pattern had worse sleep quality.

PMID- 23157866
TI  - [The effects of breastfeeding on asthma and asthma related symptoms among
      children].
AB  - OBJECTIVE: To evaluate the effect of breastfeeding on asthma and asthma related
      symptoms among children. METHODS: Using a cluster random sampling method, 2
      elementary schools and 1 kindergarten were randomly selected from each of the 5
      districts of Shenyang, and a total of 10 elementary schools and 5 kindergartens
      were included, and 8733 children from the selected schools were recruited in this
      survey. The information about the type of feeding, living environment and
      respiratory diseases of the selected children from the time they were born was
      collected by an international standard questionnaire. Evaluating the effect of
      breastfeeding on asthma and asthma related symptoms (asthma, current asthma,
      current wheeze, persistent cough, persistent phlegm, and allergic rhinitis) by
      chi2 test and logistic regression. RESULTS: There were 8733 children involved in
      this study. The age was (8.00 +/- 2.88) years old. There were 6830 breastfed
      children. The percentage of breastfed children was 78.21%. In breastfed children,
      the prevalence of asthma, persistent phlegm and allergic rhinitis were 6.12%
      (418/6830), 3.97% (271/6830), 4.17% (285/6830), respectively. In non-breastfed
      children, the prevalence of asthma, persistent phlegm and allergic rhinitis were
      7.41% (141/1903), 6.04% (115/1903), 5.89% (112/1903), respectively. Compared to
      the non-breastfed children, the breastfed children had significantly lower
      prevalence (all P values < 0.05). After adjustment for 302 cases of atopy history
      of children's mother, the results showed that in breastfed children, the
      prevalence of asthma, persistent phlegm and allergic rhinitis were 14.69%
      (36/245), 4.08% (10/245), 7.35% (18/245), respectively. In non-breastfed
      children, the prevalence of asthma, persistent phlegm and allergic rhinitis were
      33.33% (19/57), 14.04% (8/57), 17.54% (10/57), respectively. The breastfed
      children had statistically lower prevalence (all P values < 0.05). Multivariate
      analysis showed that breastfeeding was significantly associated with lower
      prevalence of asthma (OR = 0.78, 95%CI: 0.64 - 0.96), allergic rhinitis (OR =
      0.72, 95%CI: 0.57 - 0.90), persistent cough (OR = 0.81, 95%CI: 0.69 - 0.96) and
      persistent expectoration (OR = 0.61, 95%CI: 0.48 - 0.76). CONCLUSION: Breastfed
      children had lower prevalence of asthma and asthma related symptoms compared with
      non-breastfed children.

PMID- 23157867
TI  - [Identification of genotype III Japanese encephalitis virus isolated in Zhejiang
      province].
AB  - OBJECTIVE: To investigate the molecular characteristics and genotype of Japanese
      encephalitis virus (JEV) found in vector mosquitoes in Zhejiang province from
      1982 to 1983. METHODS: A total of 3188 mosquitoes were collected in Dinghai
      district and Yiwu city in Zhejiang province, during year 1982 and 1983. The virus
      was isolated by C6/36 cell, and then identified by hemagglutination inhibition
      test. The isolated strains were activated in year 2011, and plaque forming unit
      (PFU) were applied to test the virus titer. The suckling rats were tested under
      intracranial inoculation, where PrM and E genes were amplified and sequenced.
      Their nucleotide and amino acid sequences were analyzed and compared with the JEV
      vaccine strain SA14-14-2 and the JEV isolated in Zhejiang province during 2007
      and 2010; and phylogenetic tree were constructed by bioinformatic software.
      RESULTS: From the 3188 mosquitoes captured, eleven virus strains were isolated
      and found to be able to cause cytopathogenic effect (CPE) in C6/36 cells within
      72 hours. Virus titer ranged from 2.5 to 6.47 lg PFU/ml. The suckling rats would
      die within 72 hours since the inoculation. The phylogenetic analysis with the PrM
      and E genes showed that the JEV isolated in Zhejiang during 1982 and 1983
      belonged to genotype III; while the JEV isolated in Zhejiang during 2007 and 2010
      belonged to genotype I. The analysis of E genes from 5 isolated strains found
      that the homology of nucleotide sequence was over 98.9%, and the homology of
      amino acid sequence was over 99.8%. The compare between the 5 virus strains and
      the vaccine strain SA14-14-2 found 10 common amino acid variation sites, and
      showed that the homology of nucleotide sequence was over 97.7%, and the homology
      of amino acid sequence was 99.2%. The compare between the 5 virus strains and the
      JEV isolated in Zhejiang during 2007 and 2010 found a 87.7% - 87.9% nucleotide
      homology and an over 98.8% amino acid homology. CONCLUSION: The JEV isolated from
      the mosquitoes in Dinghai district and Yiwu city between year 1982 and 1983, were
      genotype III.

PMID- 23157868
TI  - [Subtype analysis of gp41 gene of HIV-1 among men who have sex with men in
      Zhengzhou].
AB  - OBJECTIVE: This study aimed to investigate the subtype distribution of gp41 gene
      of human immunodeficiency virus-1 (HIV-1) among men who have sex with men (MSM)
      in Zhengzhou. METHODS: Thirty blood samples were collected from men who have sex
      with men infected by HIV. The complete gp41 gene was amplified by RT-PCR and
      nested-PCR and sequenced. All sequences were edited by Bioedit and subtyped with
      HIV sequence library US Los Alamos National Laboratory and online genotyping
      software provided by American National Center of Biotechnology Information.
      Phylogenetic analysis of gp41 gene was performed using the MEGA 3.1 software, and
      the genic dispersion rates among subtype of gp41 gene were analyzed. RESULTS: A
      total of eighteen gene sequences of HIV-1 gp41 gene were obtained from thirty men
      who have sex with men infected by HIV, which belonged to subtype CRF15-01B (50%
      (9/18)), CRF01-AE (22% (4/18)), CRF07-B (22% (4/18)) and B (6% (1/18)),
      respectively. The intersubtype HIV-1 strains aggregate with according reference
      strains. The genetic distance inter-subtype of subtype CRF15-01B, CRF01-AE and
      CRF07-B were 0.050 +/- 0.007, 0.052 +/- 0.009 and 0.082 +/- 0.012, respectively.
      CONCLUSION: The prevalent subtypes of HIV-1 among among MSM in Zhengzhou was
      complicated and recombinant HIV-1 strains were the most prevalent strains.

PMID- 23157869
TI  - [Evaluation of effects of combination intervention model to men who have sex with
      men].
AB  - OBJECTIVE: This study aimed to explore and evaluate the effects of combination
      intervention model conducted by Center for Disease Control and Prevention and
      activity place to men who have sex with men (MSM). METHODS: To implement one-year
      combination intervention in 4 MSM venues during May, 2009 and April, 2010.
      Meanwhile, 3 similar MSM venues were chosen as control. MSM places introduced CDC
      to consumption crowds. Experts and volunteers sent by CDC undertook health
      education programme on site and condom, lubricant, pamphlet, consultation, test
      were provided at the same time. The intervention measures applied to control only
      included providing pamphlet, condom, lubricant by volunteers. Investigations were
      conducted among subjects of combination intervention group and control group
      before (111, 120 subjects) and after (105, 98 subjects) the intervention with
      questions related to knowledge and behavior of AIDS prevention. RESULTS: After
      one-year intervention, among MSM with combination intervention, the awareness
      rate of knowledge level about acquired immune deficiency syndrome (AIDS)
      increased from 73.0% (81/111) to 91.7% (110/120), proportion of condom-use with
      male at last anal intercourse increased from 73.0% (81/111) to 85.0% (102/120),
      ratio of never-use condom with male decreased from 10.8% (11/102) to 1.7%
      (2/112), percentage of acquiring AIDS-related service and intervention improved
      significantly, acquiring condom (lubricant) increased from 70.3% (78/111) to
      85.0% (102/120), acquiring peer education increased from 10.8% (12/111) to 24.2%
      (29/120), the proportion of acquiring counseling and testing of HIV increased
      from 69.4% (77/111) to 90.8% (109/120) (all P values < 0.05). The above index
      show no statistic difference before and after the intervention (all P values >
      0.05) in control MSM venues. CONCLUSION: Combination intervention model was an
      effective intervention model contributing to an increase in knowledge of AIDS
      prevention and decreasing high risk behavior in MSM population.

PMID- 23157870
TI  - [Effect of acrolein exposure on the percentage of CD4+CD25+ regulatory T cells
      and expression of transcription factor Foxp3 in asthmatic rats].
AB  - OBJECTIVE: This work was intended to investigate the effect of acrolein fog
      exposure on the ratio of CD4+CD25+ regulatory T cells (Treg) and expression of
      transcription factor Foxp3 in asthmatic rats. METHODS: Sixty 6 - 8 weeks male
      Wistar rats were randomly divided into 4 groups according to random number table
      (15 rats for each group) which were control group (animals were treated with
      saline), aerosolized ovalbumin (OVA) exposure group, acrolein exposure group and
      combined OVA and acrolein fog exposure group, respectively. The rats were exposed
      to air or/and to saline or OVA aerosol for 6-8 weeks respectively.24 h after the
      last challenge, 4 ml of peripheral blood and lung tissue were collected from each
      rat. The percentage of CD4+CD25+ T cells was determined by flow cytometry
      analysis. The concentration of interleukin-4 (IL-4) and gamma-interferon (IFN
      gamma) in peripheral blood and lung homogenates were measured by ELISA. The
      protein expression of Foxp3 in the lung was detected by Western blotting.
      RESULTS: The percentage of CD4+CD25+T cells in aerosolized OVA group ((6.23 +/-
      1.11)%) was significantly lower than that in the normal saline group ((9.97 +/-
      1.23)%) (P < 0.01). The percentage of CD4+CD25+ T cells ((3.26 +/- 0.84)%) in OVA
      combined acrolein fog exposure group was remarkably lower than that in the
      aerosolized OVA exposure group and in the normal saline group (P < 0.01). IL-4 in
      both plasma and lung ((22.57 +/- 4.34), (0.86 +/- 0.12) ng/L) was significantly
      increased in the OVA exposed rats compared with the normal saline group ((11.57
      +/- 2.86), (0.31 +/- 0.10) ng/L) (P < 0.01). Further remarkable increase in IL-4
      of both plasma and lung tissue was observed in the group exposed to both OVA and
      acrolein ((34.32 +/- 6.21), (1.45 +/- 0.32)ng/L) compared with the aerosolized
      OVA exposure group and the normal saline group (P < 0.05). gamma-IFN of plasma
      and lung tissue in OVA exposed group ((59.67 +/- 20.12), (0.56 +/- 0.17) ng/L)
      was significantly decreased compared with the normal saline group ((151.74 +/-
      56.68), (1.54 +/- 0.21) ng/L) (P < 0.01), and a further remarkable decrease in
      IFN-gamma of plasma and lung tissue was observed in the group exposed to both OVA
      and acrolein ((10.12 +/- 2.57), (0.49 +/- 0.10) ng/L) compared with the
      aerosolized OVA exposure group and the normal saline group (P < 0.05). Protein
      expression of Foxp3 in the aerosolized OVA group (8.07 +/- 0.24) was lower than
      that in the normal saline group (10.25 +/- 0.31) (P < 0.01), while the protein
      expression of Foxp3 in OVA combined acrolein fog exposure group (6.38 +/- 0.32)
      was lower than that in the normal saline group and the aerosolized OVA exposure
      group (P < 0.01). CONCLUSION: The number of CD4+CD25+ Treg cells and the
      expression of Foxp3 were likely to be altered by acrolein fog exposure, which
      might play an important role in acrolein induced Th1/Th2 imbalance in asthmatic
      rats.

PMID- 23157871
TI  - [Effect of titanium dioxide nanoparticles on hemogram in rats with gastric
      ulcer].
AB  - OBJECTIVE: To explore the effect of titanium dioxide (TiO2) nanoparticles on
      hemogram in rats with gastric ulcer. METHODS: Physicochemical properties of TiO2
      nanoparticles were characterized. Twenty-four clear class SD male rats, aging 8
      week-old, were randomly divided into 4 groups, 6 rats for each group. 20% acetic
      acid were injected into the rats' stomach on the border of gastric body and
      pyloric antrum, and hereby established the gastric ulcer model. The rats in 4
      groups were exposed to TiO2 nanoparticles through intragastric administration at
      0, 10, 50 and 200 mg/kg body weight respectively for 30 days. Afterwards, the
      rats were conducted blood routine test and blood coagulation test for analysis.
      RESULTS: TiO2 nanoparticles were anatase crystals, closely spherical shape, whose
      average grain diameter was (75 +/- 15) nm. The levels of white blood cell (WBC)
      count ((8.48 +/- 3.28)*109/L), lymphocyte (LYM) ((6.85 +/- 2.53)*109/L), monocyte
      (MOD) ((0.27 +/- 0.12)*109/L), granulocyte (GRN) ((1.37 +/- 0.86)*109/L), red
      blood cell (RBC) ((8.20 +/- 0.49)*109/L) and hematocrit (HCT) ((45.3 +/- 1.4)%)
      in the 200 mg/kg dose group were significantly higher than those in the control
      group ((2.63 +/- 0.34)*109/L, (2.25 +/- 0.26)*109/L, (0.05 +/- 0.06)*109/L, (0.33
      +/- 0.26)* 109/L, (4.87 +/- 2.37)*109/L and (27.2 +/- 13.3)%, respectively; t
      values were -3.449, -3.825, -3.554, -3.097, -2.972 and -2.936 respectively, P
      values all < 0.05). The levels of WBC ((6.88 +/- 3.06)*109/L), MOD ((0.20 +/-
      0.07)*109/L), RBC ((7.79 +/- 0.48)*109/L) and HCT ((42.7 +/- 2.8)%) in 50 mg/kg
      dose group were also statistically higher than those in the control group (t
      values were -2.507, -2.367, -2.605 and -2.511 respectively, all P values < 0.05).
      There was no statistically difference found in other blood routine index and
      coagulation index between the three experimental groups and control group.
      CONCLUSION: The long term intake of TiO2 nanoparticles caused a statistically
      increase in the amount of WBC and RBC in rats with gastric ulcer; however, there
      was no obvious changes found in blood platelet and coagulation index.

PMID- 23157872
TI  - [Inductively coupled plasma mass spectrometry for the simultaneous determination
      of thirty metals and metalloids elements in blood samples].
AB  - OBJECTIVE: To establish an inductively coupled plasma mass spectrometry(ICP-MS)
      method for determination of 30 trace elements including As, Ba, Be, Bi, Ni, Cd,
      Co, Cr, Cs, Cu, Ga, Mn, Pb, Sr, Tl, V, Ge, Mo, Nb, Ti, W, Te, Se, Zr, In, Sb, Hg,
      Ce, La, and Sm in human blood. METHOD: The blood samples were analyzed by ICP-MS
      after diluted 1/10 with 0.01% Triton-X-100 and 0.5% nitric acid solution. Y, Rh
      and Lu were selected as internal standard in order to correct the matrix
      interference of Cr, As, Se, and Hg by a hex pole-based collision-reaction cell.
      Other elements were determined with standard method. The limits of detection,
      precision and accuracy of the method were evaluated. The accuracy was validated
      by the determination of the whole blood reference material. RESULTS: All the 30
      trace elements have good linearity in their determination range, with the
      correlation coefficient > 0.9999. The limits of detection of the 30 trace
      elements were in the range of 1.19 - 2.15 ug/L and the intra-precision and inter
      precision (relative standard deviation, RSD) were less than 14.3% (except Hg RSD
      < 21.2%, and Ni RSD < 15.4%). The spiked recovery for all elements fell within
      59.3% - 119.2%. Among the 13 whole blood reference materials, V, Cr, Mn, Co, Ni,
      Cu, As, Se, Cd, Te, and Pb (1.45, 1.19, 18.40, 0.18, 1.57, 591.00, 2.97, 61.00,
      0.35, 1.86, and 9.70 ug/L respectively) fell within the acceptable range and the
      detection results of Hg (0.59 ug/L) and Mo (1.59 ug/L) were slightly beyond the
      range. CONCLUSION: This method was simple, fast and effective. It can be used to
      monitor the multi-elementary concentration in human blood.

PMID- 23157873
TI  - [Immuno-affinity chromatographic purification: the study of methods to test
      citrinin in monascus products by high performance liquid chromatography].
AB  - OBJECTIVE: To establish a method to test citrinin (CIT) in monascus products by
      immuno-affinity chromatography (IAC)-high performance liquid chromatography
      (HPLC), and to detect the content of CIT in monascus products in Fujian province.
      METHODS: IAC-HPLC was applied to detect the CIT content in monascus products. The
      conditions to use HPLC were as follows: C(18) reversed-phase chromatographic
      column, 150.0 mm*4.6mm*3 um; mobile phase: the volume ratio of acetonitrile and
      0.1% phosphoric acid solution at 65:35; isocratic elution; column temperature: 28
      degrees C; flow velocity: 0.8 ml/min; fluorescence detector, excitation
      wavelength (lambda(ex)) was 331 nm and emission wavelength (lambda(em)) was 500
      nm. The standard curved was established by the linear regression of peak area (Y)
      to CIT content (X, ng/ml). The accuracy and precision of the method would then be
      verified. And 32 kinds of monascus products were determined and their color
      values were compared by this method. RESULT: The standard curve established in
      this study was Y = 4634.8X-136.42, r = 1.000; whose limits of detection was 20
      ug/kg and the limits of qualification was 64 ug/kg. In the range between 200 and
      800 ug/kg, the standard recovery rate was 98.9% - 110.0% (n = 3), and the
      relative standard deviation (RSD) was 0.51% - 1.76%. Out of the 32 samples, CIT
      was detected from 11 samples of monascus rice, 9 samples of monascus powder and 5
      samples of monascus pigments, the content was around 0.212 - 14.500 mg/kg. 4 out
      of 7 functional monascus samples were detected out CIT, whose content at 0.142 -
      0.275 mg/kg. CONCLUSION: The method to detect CIT in monascus products by IAC
      HPLC has been established.

PMID- 23157874
TI  - Who uses complementary and alternative therapies in regional South Australia?
      Evidence from the Whyalla Intergenerational Study of Health.
AB  - OBJECTIVE: o assess the prevalence of complementary and alternative medicine
      (CAM) and service use for people with a chronic disease in rural and regional
      Australia, where reported prevalence of CAM use is higher. METHODS: ata were from
      the Whyalla Intergenerational Study of Health, a population representative cross
      sectional study of 1146 people recruited in 2008-2009. Self-reported chronic
      disease diagnosis and health service use including CAM use were collected.
      Complementary and other medicines were recorded at a clinic visit in a reduced
      sample (n=722) and SF36 data were collected by questionnaire. RESULTS: round 32%
      of respondents reported complementary medicine use and 27% CAM service use. There
      was no difference in the overall prevalence of CAM use among those with and
      without a chronic disease (OR 0.9, 95% CI 0.7-1.3). Greater age- and sex-adjusted
      use of complementary medicines was associated with the ability to save money (OR
      1.75, 95% CI 1.17-2.63), but not with any other socioeconomic position indicator.
      Those who reported using prescribed medication were more likely to report using
      complementary medicines (OR 2.09, 95% CI 1.35-3.24). CONCLUSIONS: he prevalence
      of CAM use in this regional community appeared lower than reported in similar
      communities outside of South Australia. Mainstream medicine use was associated
      with complementary medicine use, increasing the risk of an adverse drug
      interaction. This suggests that doctors and pharmacists should be aware of the
      possibility that their clients may be using complementary medicines, and the need
      for vigilance regarding potential side effects and interactions between
      complementary and mainstream therapies.

PMID- 23157875
TI  - Strong interaction between T allele of endothelial nitric oxide synthase with B1
      allele of cholesteryl ester transfer protein TaqIB highly elevates the risk of
      coronary artery disease and type 2 diabetes mellitus.
AB  - BACKGROUND: The present study was conducted to investigate the possible outcome
      of interaction between endothelial nitric oxide (NOS3) G894T and cholesteryl
      ester transfer TaqIB variants on the risk of coronary artery disease (CAD) and
      type 2 diabetes mellitus (T2DM). The sample included a total of 207 CAD patients
      (102 CAD patients with T2DM and 105 CAD patients without T2DM). There were also
      101 patients with T2DM and 92 age- and sex-matched healthy individuals as
      controls. All study participants were from Western Iran. The sample was genotyped
      by polymerase chain reaction-restriction fragment length polymorphism. RESULTS:
      The presence of NOS3 T allele was not associated with the risk of CAD or T2DM,
      and the CETP B1 allele was only significantly associated with the increased risk
      of CAD in total CAD patients (odds ratio (OR) = 5.1, p = 0.019). However, the
      concomitant presence of both CETP B1 and NOS3 T alleles significantly increased
      the risk of CAD in total CAD patients (OR = 18.1, p < 0.001), in CAD patients
      without T2DM (OR = 27.1, p = 0.03), and in CAD patients with T2DM (OR = 13.5, p =
      0.002). Also, the presence of both alleles increased the risk of T2DM (OR = 12, p
      = 0.004). CONCLUSIONS: Our findings, for the first time, indicate that NOS3 T
      allele strongly interacts with CETP B1 allele to augment the risk of CAD and T2DM
      in the population of Western Iran.

PMID- 23157876
TI  - Transformation of traditional knowledge of medicinal plants: the case of
      Tyroleans (Austria) who migrated to Australia, Brazil and Peru.
AB  - BACKGROUND: In ethnobotanical research, the investigation into traditional
      knowledge of medicinal plants in the context of migration has been of increasing
      interest in recent decades since it is influenced and changed by new
      environmental and social conditions. It most likely undergoes transformation
      processes to match the different living circumstances in the new location. This
      study compares the traditional knowledge of medicinal plants held by Tyroleans -
      and their descendants - who emigrated to Australia, Brazil and Peru at different
      time scales. The study's findings allow a discussion of the complexities and
      dynamics that influence this knowledge within the context of long-distance
      migration. METHODS: Information was obtained from 65 informants by free-listing,
      semi-structured interviews and non-participatory observation in Tyrol (Austria)
      and the migrants' countries: Australia, Brazil and Peru. The collected data was
      analysed using different quantitative approaches, including statistical tests,
      and compared between the countries of investigation. RESULTS: All respondents in
      all four investigation areas claimed that they had knowledge and made use of
      medicinal plants to treat basic ailments in their day-to-day lives. Informants
      made 1,139 citations of medicinal plants in total in free lists, which correspond
      to 164 botanical taxa (genus or species level) in Tyrol, 87 in Australia, 84 in
      Brazil and 134 in Peru. Of all the botanical taxa listed, only five (1.1%) were
      listed in all four countries under investigation. Agreement among informants
      within free lists was highest in Tyrol (17%), followed by Peru (12.2%), Australia
      (11.9%) and Brazil (11.2%). The proportion of agreement differs significantly
      between informants in Australia and Tyrol (p = 0.001), Brazil and Tyrol (p =
      0.001) and Peru and Tyrol (p = 0.001) and is similar between informants in the
      migrant countries, as indicated by statistical tests. We recorded 1,286 use
      citations according to 744 different uses (Tyrol: 552, Australia: 200, Brazil:
      180, Peru: 357) belonging to 22 different categories of use. Use values are
      significantly different between Tyrol and Australia (p < 0.001) but not between
      Tyrol and Brazil (p = 0.127) and Tyrol and Peru (p = 0.853). The average
      informant agreement ratio (IAR) in Tyrol is significantly higher than in
      Australia (p = 0.089) and Brazil (p = 0.238), but not Peru (p = 0.019).
      CONCLUSIONS: Changing ecological and social conditions have transformed and
      shaped traditional knowledge of medicinal plants through adaptation processes to
      match the new circumstances in the country of arrival. Continuation, substitution
      and replacement are strategies that have taken place at different rates depending
      on local circumstances in the research areas. Traditional knowledge of medicinal
      plants acquired in the home country is continuously diminishing, with its
      composition influenced by urbanisation and ongoing globalisation processes and
      challenged by shifts from traditional healing practices to modern healthcare
      facilities.

PMID- 23157878
TI  - [The development on surveying and monitoring physical fitness and health among
      Chinese students and the establishment of its system].

PMID- 23157877
TI  - An algorithm for longitudinal registration  of PET/CT images acquired during
      neoadjuvant chemotherapy in breast cancer: preliminary results.
AB  - BACKGROUND: By providing estimates of tumor glucose metabolism, 18F
      fluorodeoxyglucose positron emission tomography (FDG-PET) can potentially
      characterize the response of breast tumors to treatment. To assess therapy
      response, serial measurements of FDG-PET parameters (derived from static and/or
      dynamic images) can be obtained at different time points during the course of
      treatment. However, most studies track the changes in average parameter values
      obtained from the whole tumor, thereby discarding all spatial information
      manifested in tumor heterogeneity. Here, we propose a method whereby serially
      acquired FDG-PET breast data sets can be spatially co-registered to enable the
      spatial comparison of parameter maps at the voxel level. METHODS: The goal is to
      optimally register normal tissues while simultaneously preventing tumor
      distortion. In order to accomplish this, we constructed a PET support device to
      enable PET/CT imaging of the breasts of ten patients in the prone position and
      applied a mutual information-based rigid body registration followed by a non
      rigid registration. The non-rigid registration algorithm extended the adaptive
      bases algorithm (ABA) by incorporating a tumor volume-preserving constraint,
      which computed the Jacobian determinant over the tumor regions as outlined on the
      PET/CT images, into the cost function. We tested this approach on ten breast
      cancer patients undergoing neoadjuvant chemotherapy. RESULTS: By both qualitative
      and quantitative evaluation, our constrained algorithm yielded significantly less
      tumor distortion than the unconstrained algorithm: considering the tumor volume
      determined from standard uptake value maps, the post-registration median tumor
      volume changes, and the 25th and 75th quantiles were 3.42%  (0%, 13.39%) and
      16.93% (9.21%, 49.93%) for the constrained and unconstrained algorithms,
      respectively (p = 0.002), while the bending energy (a measure of the smoothness
      of the deformation) was 0.0015 (0.0005, 0.012) and  0.017 (0.005, 0.044),
      respectively (p = 0.005). CONCLUSION: The results indicate that the constrained
      ABA algorithm can accurately align prone breast FDG-PET images acquired at
      different time points while keeping the tumor from being substantially compressed
      or distorted. TRIAL REGISTRATION: NCT00474604.

PMID- 23157879
TI  - [The trend analysis of overweight and obesity in Chinese students during 1985 -
      2010].
AB  - OBJECTIVE: To analyze the trend of overweight and obesity in students in China
      during 1985 - 2010. METHODS: The data were from Chinese National Survey on
      Students Constitution and Health in 1985, 1995, 2000, 2005 and 2010, and the
      sample sizes were 204 977, 216 786, 234 421, 215 319, respectively. BMI was
      calculated with height and weight. The prevalence of overweight and obesity as
      well as the rates of increase were described based on the BMI percentile criteria
      of Working Group on Obesity in China (WGOC). RESULTS: In 2010, the prevalence of
      overweight and obesity in four groups students (urban boys, urban girls, rural
      boys, and rural girls aged 7 - 18 years) were 23.23% (12 503/53 830), 13.76% (7
      414/53 857), 12.72% (6 839/53 744), 8.56% (4 612/53 888), respectively, which
      were higher in boys and urban, and reached the peak 17.14% (18 463/107 741) in
      students aged 7 - 12 years. The prevalences of obesity were 0.44% (8/1800) -
      21.67% (390/1800) among children aged 7 - 18 years in different provinces. The
      prevalence of overweight and obesity during 1985 - 1995, 1995 - 2000, 2000 - 2005
      and 2005 - 2010 increased 0.10%, 0.30%, 0.23%, 0.23%, respectively, and the
      increase rate was higher in urban than in rural during 1985 - 2005. During 1985 -
      1995, the increase rate of obesity in four groups students were 0.20%, 0.13%,
      0.05% and 0.03%, respectively. During 2005 - 2010, the increase rates of obesity
      in four groups of students were 0.30%, 0.10%, 0.34%, 0.17%, respectively, and the
      increase rate was higher in rural than in urban. CONCLUSION: The prevalence of
      obesity among 7 - 18 years-old children increased rapidly during the 1985-2000,
      and the increase rate of obesity in rural exceeded that in urban during 2005 -
      2010.

PMID- 23157880
TI  - [Analysis of current situation of physical activity and influencing factors in
      Chinese primary and middle school students in 2010].
AB  - OBJECTIVE: To find out the current situation of physical activity and its
      influencing factors among Chinese primary and middle school students. METHODS: A
      total of 166 812 students aged 9 - 18 finished the questionnaires of physical
      activities and lifestyle behaviors who were selected from "2010 National Physical
      Fitness and Health Surveillance". The subjects were sampled by stratified cluster
      sampling method in 30 provinces (autonomous regions, municipalities) except
      Tibet. The physical activity for a total of at least 60 minutes per day,
      attitudes on physical activity, parents' supports toward physical activity of
      children, development of school physical education, the schoolwork burden and
      sedentary lifestyle were all analyzed. Logistic regression was used to analyze
      the association between the physical activity for a total of at least 60 minutes
      per day and individual, family, school and sedentary behavior. RESULTS: A total
      of 22.7% (37 867/166 757) of primary and middle school students aged 9 - 18 had
      been physically active doing any kind of physical activity for a total of 60
      minutes or more per day, the prevalence was higher among male (25.4%, 21 086/83
      159) than female (20.1%, 16 781/83 598) students (P < 0.05). In the 9 - 12 age
      group, the prevalence was higher among urban (37.6%, 5 980/15 912) than rural
      (32.0%, 4 917/15 375) students (P < 0.05), but in the 16 - 18 age group, the case
      was opposite. The prevalence of doing physical activity for a total of 60 minutes
      or more per day among students who liked physical education (23.7%, 11 866/50
      073), were willing to participate in the extracurricular sports activities
      (23.2%, 13 460/57 907), and were willing to participate long running exercise
      (26.9%, 9 185/34 153) was higher than those who dislike physical education
      (15.9%, 589/3705), were not willing to participate in the extracurricular sports
      activities (15.9%, 567/3565), and were not willing to participate long running
      exercise (12.1%, 2 246/18 493), respectively. The prevalence was higher among
      students whose parents supported their physical activity (20.4%, 15 148/74 312)
      than those students without parents' support (17.5%, 1626/9270) (P < 0.05). And
      the prevalence was higher among students whose parents often took part in the
      physical activity (22.7%, 12 864/56 769) than those students whose parents did
      not (14.6%, 3 906/26 780) (P < 0.05). Logistic regression analysis (adjusted sex,
      age and urban or not) demonstrated that variables associated with physical
      activity for a total of 60 minutes or more per day were the initiative will on
      the physical activity and parental physical activity (OR: 1.478, 95%CI: 1.398 -
      1.562). The students without adequate physical education class in school were
      less likely to do physical activity for a total of 60 minutes or more per day
      than those who with adequate physical education class in school (OR: 0.536,
      95%CI: 0.523 - 0.550), and the students in the school with the phenomenon of
      "crowding out" or "no" physical education were less likely to do physical
      activity for a total of 60 minutes or more per day than those whose school
      without these with phenomenon (OR: 0.712, 95%CI: 0.666 - 0.761). The heavy
      homework burden (OR: 0.926, 95%CI: 0.899 - 0.953) and long homework time (OR:
      0.879, 95%CI: 0.853 - 0.906) were reversely related to the physical activity.
      CONCLUSION: The prevalence of having been physically active for a total of 60
      minutes per day in Chinese students is still low. The strong initiative will on
      the physical activity, parental physical activity, and better school sports
      atmosphere are good for students to carry out physical activity, and the students
      with the heavy homework burden and long homework time are less likely to take
      part in the physical activity.

PMID- 23157881
TI  - [Behavioral risk factors for overweight and obesity among Chinese primary and
      middle school students in 2010].
AB  - OBJECTIVE: To explore the associations between behavioral risk factors and
      overweight and obesity among Chinese primary and middle school students in 2010.
      METHODS: A total of 149 912 primary and middle school students aged 9 - 18 were
      selected from "2010 National Physical Fitness and Health Surveillance" while
      underweight students excluded. Questionnaires and height, weight and other
      physical index were performed. Logistic regression was used to analyze the
      association between overweight, obesity and sleep time, diet, physical exercise
      intention and behavior as well as sedentary behavior. RESULTS: Of students
      surveyed, the proportion of short sleep time was higher in obese students than in
      normal weight students, the prevalence of short sleep time was 93.60% (118
      394/126 491), 94.39% (15 053/15 947) and 95.09% (6782/7132) in normal weight,
      overweight and obese students, respectively (P < 0.05); the proportion of egg
      intake with no more than 3 times per week was lower in obese students than in
      normal weight students (56.49% (4025/7125) vs 65.25% (82 518/126 464)) (P <
      0.05); the proportion of never drinking milk was lower in obese students than in
      normal weight students (7.08% (505/7134) vs 7.55% (9 545/126 503)) (P < 0.05);
      and when compared with those of normal (29.53%, 37 354/126 482), more overweight
      students reported that they had spent 2 or more hours on homework (30.17%, 4
      809/15 941) (P < 0.05). The proportions of physical activity intentions were
      significantly lower in obesity group of male students than those of normal male
      group, and the proportion of liking physical education, being willing to
      participate in the extracurricular sports activities, and being willing to
      participate long running exercise was 67.7% (4828/7134), 71.2% (5083/7135) and
      35.9% (2560/7135) in obese students compared with 68.6% (86 776/126 511), 72.6%
      (91 814/126 509) and 47.4% (59 914/126 512) in normal weigh students,
      respectively. In the 13 - 15 age group, the proportion of having been physically
      active for a total of at least 60 minutes per day was lower in obese group
      (19.87%, 376/1893) than in normal group (20.66%, 8 253/39 941) (P < 0.01).
      Logistic regression analysis showed that the students with short sleep time were
      more likely to get obesity than those without short sleep time (adjusted odds
      ratio (AOR): 1.11, 95%CI: 1.00 - 1.25). Egg intake with no more than 3 times per
      week was negatively associated with the probabilities of being at risk for
      obesity (AOR: 0.88, 95%CI: 0.83 - 0.92), while, never drinking milk was
      independently related to obesity (AOR: 1.14, 95%CI: 1.03 - 1.25). Disliking
      physical education (AOR: 1.23, 95%CI: 1.16 - 1.30), unwilling to participate long
      running exercise (AOR: 2.16, 95%CI: 2.05 - 2.28) and spending 2 or more hours on
      homework (AOR: 1.09, 95%CI: 1.02 - 1.15) were independently related to obesity.
      The patterns of influence factors in different groups were not alike. CONCLUSION:
      Overweight and obesity prevalence was higher in China's primary and middle school
      students in 2010, and the bad dietary behavior, static life style were highly
      interconnected.

PMID- 23157882
TI  - [Relationship between obesity, overweight and physical function in students of
      Han nationality aged 7 - 18 years in 2010].
AB  - OBJECTIVE: To study the effects of overweight and obesity on physical function
      (including systolic blood pressure (SBP), diastolic blood pressure (DBP), pulse,
      weight vital capacity index) in children and adolescents. METHODS: The data of
      2010 Chinese National Survey on Students Constitution and Health was analyzed.
      The samples of overweight and normal-weight group were randomly selected from the
      data by matching gender, urban or rural for getting the same number sample size
      as obese group (10 601 each group). The students aged 7 - 18 years were
      classified into 3 groups by BMI percentiles (P5, P15, P25, P50, P75, P85 and
      P95), to analyze the change of physical function along with BMI percentile.
      RESULTS: Compared to the normal-weigh group, SBP of the obese boys of all age
      groups increased by 8.0 - 12.0 mm Hg, DBP increased by 4.7 - 5.9 mm Hg, while SBP
      of the obese girls increased by 7.5 - 11.6 mm Hg, DBP increased by 4.7 - 6.1 mm
      Hg, with statistical significance (P < 0.05). In 13 - 15-year group, pulse of
      obese boys was 0.8 times/min higher than that of normal-weight. In 16 - 18-year
      group, pulse of obese boys was 1.1 times/min higher than that of overweight or
      normal-weight, while pulse of obese girls were 1.5 and 1.7 times/min higher than
      that of overweight and normal-weight, respectively (P < 0.05). Pulses in boys
      aged 7 - 9 years when BMI were P5, P50, P(95) were 87.63, 87.00, 87.83 times/min,
      and pulses in boys aged 10 - 12 were 85.66, 85.30, 85.43 times/min, respectively.
      Pulses in boys aged 13 - 15 years when BMI were P5, P50, P95 were 82.60, 81.39,
      82.34 times/min, and pulses in boys aged 16 - 18 years were 80.15, 79.00, 79.98
      times/min. In both boys and girls of all age groups, weight vital capacity index
      had the trend of obese < overweight < normal-weight (P < 0.05). Compared to the
      normal-weight group, weight vital capacity index of overweight boys decreased by
      6.4 - 8.4 ml/kg, that of obese boys decreased by 11.9 - 14.8 ml/kg, while that of
      overweight girls decreased by 5.3 - 7.7 ml/kg, that of obese girls decreased 11.0
      - 11.5 ml/kg. CONCLUSION: Compared to the normal-weight, overweight and obese
      children and adolescents had elevated blood pressure, increased pulse, decreased
      weight vital capacity index.

PMID- 23157883
TI  - [Trends in dietary protein intake among Chinese children and adolescent between
      1991 and 2009].
AB  - OBJECTIVE: To examine dietary protein intake and its trend between 1991 and 2009
      among Chinese children and adolescents aged 6 to 17 years. METHODS: Consecutive 3
      d-24 hr Dietary Recall and household income data of 14 053 children from the
      seven waves of the China Health and Nutrition Survey (CHNS), 1991, 1993, 1997,
      2000, 2004, 2006 and 2009 were used to describe long-term changes in dietary
      protein intake, percentage energy, and food sources. RESULTS: The median of
      dietary protein intake of Chinese children and adolescents decreased from 60.0
      g/d in 1991 to 52.6 g/d in 2009 (chi2 = 109.0, P < 0.01). The dietary protein
      intake among children in rural areas and in low-income households decreased 8.8
      g/d (chi2 = 74.8, P < 0.01) and 9.8 g/d (chi2 = 100.5, P < 0.01) respectively.
      The percentage of total energy intake from protein was 11.3%-13.0%. The
      percentage of protein intake equal or higher than Recommended Nutrient Intake of
      protein decreased from 29.5% in 1991 to 19.2% in 2009 (chi2 = 259.6, P < 0.01).
      Furthermore, the proportion of high-quality dietary protein increased rapidly.
      The percentage of animal protein increased from 12.3% in 1991 to 32.2% in 2009
      (chi2 = 750.3, P < 0.01), while no big increase in soybean protein (lower than
      5.0%). CONCLUSION: There is a decreasing trend in dietary protein intake among
      Chinese children from 1991 to 2009. The high-quality protein intake was improved
      but we should be concerned about the high proportion of animal protein. The
      children living in low-income households and in rural areas may be at risk of
      inadequate dietary protein.

PMID- 23157884
TI  - [Comprehensive evaluation of complementary feeding behavior for infants in urban
      and rural areas of Chengdu in 2011].
AB  - OBJECTIVE: To study the status and problems of complementary feeding behavior for
      infants aging between 6 - 24 month-old in urban and rural areas of Chengdu in
      2011. METHODS: A total of 1283 infants aging between 6 - 24 month-old, including
      601 from urban area and 682 from rural area, were randomly selected by stratified
      cluster random sampling method, and divided into three groups as 6 - 8, 9 - 11
      and 12 - 24 month-old groups, between March and April in 2011. Information of
      complementary feeding behavior were collected by questionnaire, and then
      assessed, quantified and compared by standards. The evaluation system was
      established (the total score was 24), and was used to assess among children aging
      6 to 24 month-old in urban and rural areas in Chengdu. RESULTS: The average score
      for infants in Chengdu was 18.6 +/- 2.5, accounting for 77.6% of the total score.
      The scores of food selection and preparation were highest (90.7% of total score)
      among the behavior, and the scores of caregiver's behavior, infants behavior,
      feeding environment and environmental hygiene were low (about 75.2% - 77.6% of
      total score). The average score in urban and rural groups were separately 19.8 +/
      2.1 and 17.6 +/- 2.4, the score in urban group was higher than that in rural
      group (P < 0.05), occupying total score 82.3%, 73.4%, respectively. The average
      score in 6 - 8 month, 9 - 11 month and 12 - 24 month groups were separately 18.9
      +/- 2.3, 19.1 +/- 2.4, and 18.2 +/- 2.6, occupying total score 78.9%, 79.4% and
      75.7%, respectively. The score in 6 - 8 and 9 - 11 month groups were higher than
      that in 12 - 24 month group (P < 0.01). The pass rate (above 60% of total score)
      was 94.2% and excellent rate (above 80% of total score) was 44.8% in Chengdu. The
      excellent rate in urban and rural groups were separately 65.7% and 26.4% (chi(2)
      = 199.825, P < 0.01). CONCLUSION: The complementary feeding behavior for infants
      was not optimistic in Chengdu, and the behavior was even worse in rural areas and
      among elder infants groups.

PMID- 23157885
TI  - [Study on antibody response to revaccination of hepatitis B vaccine among firstly
      low-response adults].
AB  - OBJECTIVE: To evaluate and compare the antibody to hepatitis B virus (HBV)
      surface antigen (anti-HBs) response and the influent factors of revaccination of
      4 kinds of hepatitis B vaccine (HepB) among firstly low-response adults. METHODS:
      A total of 11 590 adults who were 18 - 49 years old, never received HepB
      vaccination, without HBV infection history, HBs-Ag negative, and had been living
      at 3 towns of Zhangqiu county in Shandong province Ji'nan city for more than half
      a year, were selected in the study in July, 2009. Self-designed questionnaire was
      used to select the basic information of the subjects. The subjects were divided
      into 4 groups by cluster sampling, and were vaccinated according to the "0-1-6"
      immune procedure with 10 ug HepB made by recombinant deoxyribonucleic acid
      techniques in Saccharomyces Cerevisiae (HepB-SC), 10 ug HepB made by recombinant
      deoxyribonucleic acid techniques in Hansenula Polymorpha (HepB-HP), 20 ug HepB-SC
      and 20 ug HepB made by recombinant deoxyribonucleic acid techniques in Chinese
      hamster ovary cell (HepB-CHO), 3 doses respectively. The adults who were low
      response to the primary hepatitis B vaccination (10 mU/ml <= anti-HBs < 100
      mU/ml) were divided into four groups by cluster sampling. These groups were
      revaccinated with one-dose of above-mentioned four kinds of HepB respectively.
      Blood samples were drawn from each person one month after the revaccination. Anti
      HBs was detected by chemiluminescence microparticle immunoassay and compared by
      the vaccine type. The influence factors about antibody response were also
      analyzed. RESULTS: Out of the 11 590 subjects, 8592 adults had accepted the
      primary vaccination of hepatitis B and been collected the blood samples; among
      whom, 1306 subjects showed low-response, at the rate of 15.20%. A total of 1034
      low-response subjects accepted secondary strengthened vaccination and were
      collected blood samples; 55.13% of them showed anti-HBs seroconversion (anti-HBs
      >= 100 mU/ml); while the seroconversion rate in each group was 44.54% (106/238)
      in 10 ug HepB-SC group, 57.14% (156/273) in 10 ug HepB-HP group, 56.08% (143/255)
      in 20 ug HepB-SC group and 61.57% (165/268) in 20 ug HepB-CHO group,
      respectively. There was significant difference among the groups (chi2 = 17.14, P
      < 0.01). The rates of anti-HBs seroconversion were significantly higher in 10 ug
      HepB-HP and 20 ug HepB-CHO groups than it in 10 ug HepB-SC group (chi2 were 8.09
      and 14.70 respectively, P < 0.01). The geometric mean concentration (GMC) of anti
      HBs was 178.24 mU/ml among the low-responders after one dose of revaccination.
      The GMC was 109.77, 243.50, 144.98 and 242.83 mU/ml in 10 ug HepB-SC group, 10 ug
      HepB-HP group, 20 ug HepB-SC group and 20 ug HepB-CHO group, respectively. There
      was significant difference among groups (F = 9.52, P < 0.01). CONCLUSION: Anti
      HBs response could be strengthened effectively after one-dose of HepB
      revaccination among the low-response adults. Many factors like the vaccine types
      could effect the immune effects to HepB. A better response could be achieved if
      the 20 ug HepB-CHO or 10 ug HepB-HP was used for revaccination.

PMID- 23157886
TI  - [Study on family aggregation and risk factors of hepatitis B virus transmission
      in Chaoyang district, Beijing].
AB  - OBJECTIVE: To explore the family aggregation and risk factors of hepatitis B
      virus (HBV) transmission in Chaoyang district of Beijing. METHODS: A total of
      5266 families were randomly selected for the multi-stage cluster sampling study
      in Chaoyang district of Beijing in 2010. The family members who aged between 1
      and 70 years old and lived constantly in Beijing for over half a year, were
      recruited as subjects. There were 14 491 subjects in total, including temporary
      residents who did not have Beijing household account, except foreigners. 5 ml
      venous blood was drawn from every subject. A self-designed questionnaire was used
      to collect the basic information of the population and the risk factors of the
      hepatitis B transmission. Microparticle enzyme-linked immunoassay was applied to
      test five indicators of hepatitis B. Negative binomial distribution test was used
      among the HBsAg positive families to calculate the family aggregation rate of
      hepatitis B. Single factor analysis and multi-factor logistic regression model
      were used to analyze the risk factors of HBV transmission. RESULTS: In all, 308
      out of 5266 families had HBsAg positive members, accounting for 5.85%.383 out of
      14 410 subjects were HBsAg positive, rating at 2.66%. The HBsAg positive rate
      among subjects under 14 years old was the lowest, at 0.56% (9/1603); and the
      positive rate among subjects aging between 35 and 44 years old was the highest,
      at 4.27% (47/1029). Negative binomial distribution test showed that the family
      aggregation rate of HBV infection was 7.66% (chi2 = 15.10, P < 0.05). The
      analysis of family aggregation of HBsAg positive showed that 17.39% (8/46) of the
      transmission was from father to child, 13.04% (6/46) was from mother to child,
      30.44% (14/46) was between couples, and another 39.13% (18/46) was between
      siblings or other relatives. Both single factor analysis and multi-factor
      logistic regression analysis showed that hepatitis B positive family members (OR
      = 5.40, 95%CI: 5.24 - 5.55), hepatitis B positive friends and colleagues (OR =
      1.55, 95%CI: 1.11 - 1.99) and blood donation and transfusion history (OR = 1.96,
      95%CI: 1.76 - 2.15) were the risk factors of HBV infection. CONCLUSION: HBV
      transmission showed family aggregation in Beijing, however, the risk factors
      needed further studies.

PMID- 23157887
TI  - [Health literacy and its relative factors to residents in three cities in China].
AB  - OBJECTIVE: To measure, evaluate health literacy and discover its relative factors
      among residents of three cities in China. METHODS: Multiple cluster sampling was
      employed and 3300 respondents were surveyed by self-designed questionnaires in
      Beijing, Datong and Shenzhen city during May to September in 2011. Information on
      demographic characteristics, health knowledge and health literacy was collected.
      Respondents' health literacy scores were statistically reported and evaluated
      referring to education level. To explore relative factors of health literacy,
      multiple linear regression model with score of health literacy as dependent
      variable, respondents' demographic characteristics and health knowledge as
      independent variables was built by multiple linear regression analysis. RESULTS:
      Questionnaires were conducted among 3300 residents and resulted in 90.9%
      (3000/3300) qualified sample return. Respondents were (31.6 +/- 12.0) (15 - 65)
      years old, who got (19.92 +/- 5.17) (2 - 28) scores in the health literacy test
      with an average correct rate of 71.1%. The proportion of subjects with low (<
      20.5 grades), medium (20.5 - 24.5 grades), and high (> 24.5 grades) level of
      health literacy were 46.6% (1398/3000), 33.1% (993/3000) and 20.3% (609/3000)
      respectively. The multiple linear regression model showed that positive
      correlation factors of health literacy included health knowledge (beta = 0.28),
      education level (beta = 0.28), income (beta = 0.14), gender (beta = 0.05),
      nationality (beta = 0.05), registered permanent residence (beta = 0.05) (all P
      values < 0.05) and the negative correlated factors included age (beta = -0.28),
      occupation (beta = -0.05), respectively (all P values < 0.05). CONCLUSION: Over
      50% residents in the three studied cities had medium and above health literacy.
      The positive correlated factors of health literacy included health knowledge,
      education level, income, gender, nationality, registered permanent residence and
      the negative correlated factors included age and occupation.

PMID- 23157888
TI  - [An association study between transforming growth factor-beta1 receptor 2 gene
      polymorphisms and essential hypertension].
AB  - OBJECTIVE: To evaluate the association between two single nucleotide
      polymorphisms located in the promoter of transforming growth factor-beta1
      receptor 2 (TGFBR2) gene and hypertension in Han Chinese population. METHODS: The
      subjects were recruited from the population of cluster sampling survey for
      essential hypertension (EH) in two townships of Yixing city, Jiangsu province in
      2009. Overall, 2012 patients with hypertension and 2116 age (+/- 2 years) and sex
      matched unrelated controls were selected. Epidemiological data, physical
      measurements results and serum glucose and lipid biomarker were collected and
      detected. Linkage disequilibrium (LD) analysis were applied and two tagging
      single nucleotide polymorphisms (tagSNP) in 5' upstream of TGFBR2 gene
      (rs6785358, -3779A/G; rs764522, -1444C/G) were selected for genotyping and
      analyzing for the association with hypertension. RESULTS: The frequencies of AA,
      AG, GG in case and control of rs6785358 were 1455 (72.3%), 517 (25.7%), 40 (2.0%)
      and 1582 (74.8%), 490 (23.2%), 43 (2.0%) respectively, and CC, CG, GG of rs764522
      were 1524 (75.7%), 464 (23.1%), 24 (1.2%) and 1654 (78.2%), 436 (20.6%), 26
      (1.2%) respectively. SNP rs764522 was significantly associated with EH and OR
      (95%CI) were 1.17 (1.01 - 1.36) (P < 0.05) in dominant model after adjustment for
      confounding factors such as age, sex, glucose, lipids, smoking and alcohol
      drinking. Further stratification analysis by age, sex, smoking and alcohol
      drinking indicated that individuals carrying G allele (CG/GG genotype) of SNP
      rs764522 had higher susceptibility to EH than CC genotype (OR = 1.21, 95%CI: 1.01
      - 1.45) (P < 0.05) in >= 55 years group. No statistical significance was detected
      in the distribution of genotypes and allele frequencies for SNP rs6785358 between
      cases and controls (P > 0.05). Haplotype analysis showed that no significant
      frequency difference of haplotype structured by rs6785358 and rs764522 was found
      between cases and controls (P > 0.05), and no significant blood pressure change
      was found between genotype variations of rs6785358 and rs764522 (P > 0.05).
      CONCLUSION: SNP rs764522 of TGFBR2 gene is associated with increased risk of EH
      in elderly Han Chinese population.

PMID- 23157889
TI  - [A case-control study on association of SULT1A1 polymorphism, smoked meat intake
      with breast cancer risk].
AB  - OBJECTIVE: To assess the association of smoked meat intake, SULT1A1 polymorphism
      as well as their combined effects with breast cancer risk. METHODS: A total of
      400 newly diagnosed breast cancer cases from a cancer hospital in Sichuan
      province and 400 healthy controls from participants of physical examination in a
      hospital in Chengdu city were recruited from May 2007 to July 2009. A valid
      questionnaire was designed to collect their demographic characteristics and
      breast cancer risk factors. Daily intake of foods was collected using semi
      quantitative frequency questionnaire and then the daily intake of smoked meat was
      calculated and transformed to energy-adjusted smoked meat intake by the residual
      method. Gene sequencing was used to analyze SULT1A1 Arg213His genotypes.
      Multivariable conditional logistic regression was used to estimate adjusted odds
      ratios (ORs) and 95% confidence intervals (95%CIs). RESULTS: The energy-adjusted
      daily intake of smoked meat (Median (P25, P75)) was 8.65 (3.63, 18.44) g/d in
      cases and 4.44 (0.19, 8.71) g/d in controls. The frequency of SULT1A1 variant
      allele was 14.75% (59/400) among cases and 12.75% (51/400) among controls. High
      energy-adjusted daily intake of smoked meat (>= 4.44 g/d) was significantly
      associated with breast cancer risk among premenopausal (OR = 2.31, 95%CI: 1.46 -
      3.66) and postmenopausal subjects (OR = 3.13, 95%CI: 1.89 - 5.17). High energy
      adjusted daily intake of smoked meat combined with carrying SULT1A1 variant
      allele elevated breast cancer risk among premenopausal (OR = 3.31, 95%CI: 1.66 -
      6.62) and postmenopausal subjects (OR = 3.81, 95%CI: 1.79 - 8.10). CONCLUSION:
      High smoked meat intake contributes to high risk of breast cancer. SULT1A1
      variant allele increases breast cancer risk among subjects who were exposed to
      high smoked meat intake.

PMID- 23157890
TI  - [Association between cytokines and trichloroethylene-induced hypersensitivity
      dermatitis].
AB  - OBJECTIVE: To detect the cytokines levels in serums of patients with
      trichloroethylene-induced hypersensitivity dermatitis and explore the effect
      biomarkers associated with this disease. METHODS: Twenty-two patients with TCE
      induced hypersensitivity dermatitis, twenty-two healthy TCE-exposed workers from
      the same workshops with patients and twenty-two comparable unexposed controls
      were recruited in this study. Eight cytokines in serums from all subjects were
      detected using Liquid Suspended Biochip; the correlation among the eight
      cytokines including interleukin (IL)-1beta (IL-1beta), IL-5, IL-8, IL-10,
      interferon-gamma (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha), macrophage
      chemoattractant protein-1 (MCP-1), macrophage inflammatory protein-1beta (MIP
      1beta) and the correlation between IL-5 and eosinophil count were analyzed.
      RESULTS: The medians of levels of IL-1beta, IFN-gamma, IL-5, IL-10, MCP-1, MIP
      1beta, IL-8 among patients were 0.15, 80.13, 2.95, 6.45, 83.83, 1057.90, 440.22
      pg/ml, respectively, which were higher than those among the TCE-exposed workers
      (0.09, 16.93, 0.11, 0.07, 28.75, 241.07, 28.26 pg/ml, respectively, all P values
      < 0.01) and unexposed controls (0.09, 3.14, 0.11, 0.07, 25.27, 209.64, 207.34
      pg/ml, respectively, all P values < 0.01). The median of level of TNF-alpha among
      the patients was 13.26 pg/ml, which was significantly higher than that among TCE
      exposed workers (4.87 pg/ml, P < 0.01) but not among unexposed controls; the
      median of level of IL-5 among the TCE-exposed workers was 0.11 pg/ml, which was
      significantly higher than that among the unexposed controls (0.11 pg/ml, P <
      0.01). The median of levels of IL-8 among the unexposed controls was 207.34
      pg/ml, which was significantly higher than that among the TCE-exposed workers
      (28.26 pg/ml, P < 0.01). In case group, except for correlation of TNF-alpha and
      IFN-gamma, TNF-alpha and IL-5, the significant positive correlations were found
      among any two cytokines (r(IL-1beta,IFN-gamma) = 0.500, r(IL-1beta,TNF-alpha) =
      0.348, r(IL-1beta,MCP-1) = 0.537, r(IL-1beta,MIP-1beta) = 0.477, r(IL-1beta,IL-8)
      = 0.466, r(IL-1beta,IL-5) = 0.610, r(IL-1beta,IL-10) = 0.626, r(IFN-gamma,MCP-1)
      = 0.460, r(IFN-gamma,MIP-1beta) = 0.491, r(IFN-gamma,IL-8) = 0.322, r(IFN
      gamma,IL-5) = 0.532, r(IFN-gamma,IL-10) = 0.511, r(TNF-alpha,MCP-1) = 0.325,
      r(TNF-alpha,MIP-1beta) = 0.283, r(TNF-alpha,IL-8) = 0.430, r(TNF-alpha,IL-10) =
      0.271, r(MCP-1,MIP-1beta) = 0.659, r(MCP-1,IL-8) = 0.526, r(MCP-1,IL-5) = 0.504,
      r(MCP-1,IL-10) = 0.614, r(MIP-1beta,IL-8) = 0.601, r(MIP-1beta,IL-5) = 0.451,
      r(MIP-1beta,IL-10) = 0.579, r(IL-8,IL-5) = 0.255, r(IL-8,IL-10) = 0.403, r(IL
      5,IL-10) = 0.798, all P values < 0.05). The median of level of IL-5 among the
      patients with high eosinophils counts was 8.92 pg/ml, which was significantly
      higher than that among the patients with low eosinophils counts (1.04 pg/ml, P <
      0.05). CONCLUSION: The abnormal production of IL-1beta, IFN-gamma, TNF-alpha, IL
      8, MCP-1, MIP-1beta, IL-5 and IL-10 was related with the pathogenesis of
      hypersensitivity dermatitis induced by TCE. These cytokines could be used as
      referential indexes in the early health surveillance and clinic disease
      treatment.

PMID- 23157891
TI  - [Genome-wide analysis of DNA methylation changes in the rat ovary after prenatal
      exposure to di-(2-ethylhexyl)-phthalate].
AB  - OBJECTIVE: To study the effects of prenatal exposure to Di-(2-ethylhexyl)
      phthalate (DEHP) on genome-wide epigenetic alterations in ovary of adult
      offspring rat. METHODS: Pregnant Wistar rats were randomly treated with DEHP
      (1000 mg/kg) or con oil at 12 - 17 days upon pregnance. DNA methylation changes
      in the ovary for the adult offsprings which were 70 days old were detected by Rat
      DNA methylation promoter plus CpG island arrays CpG island chip. Gene ontology
      (GO) method was performed to analyze the function of genes which were
      significantly different between exposed group and control group. Gene Igfbp1
      (insulin-like growth factor binding protein 1) and Itga3 (integrin alpha 3) were
      randomly selected and the methylation status were verified by bisulfite genomic
      sequencing (BSP). RESULTS: The methylation status were significantly different
      between exposed and control group in 406 genes (71 genes as hypermethylation and
      335 genes as hypomethylation) (P < 0.05). GO analysis revealed that molecular
      transducer activity, cell part, cell, cellular process, multicellular organismal
      process, response to stimulus, biological regulation, regulation of biological
      process, reproduction, reproductive process, and rhythmic process were involved.
      The sequencing results were consistent with the data obtained by chips.
      CONCLUSION: This study provides evidence that prenatal exposure of DEHP may be
      associated with methylation changes on the genes in the rat ovary. Genes related
      to reproductive process have highly significant methylation changes, which may
      shed new light on mechanisms of reproductive and developmental toxicity after
      prenatal exposure to DEHP.

PMID- 23157892
TI  - [Random forest analysis of high dimensional case and control study of lung
      cancer].
AB  - OBJECTIVE: To investigate the performance of random forest method as a SNP
      screening procedure in high dimensional case-control data of lung cancer.
      METHODS: This study included 500 lung cancer patients and 517 controls. A total
      of 5 ml venous blood sample was collected from each participant. The genotypes
      were classified by GoldenGate platform, and 399 SNPs were selected. The random
      forest method was first applied to reduce the dimension, and then the traditional
      logistic regression method was used to analyze the variables and the genetic
      susceptibility between lung cancer and multiple SNPs was analyzed by AUC (areas
      under receiver operation characteristics (ROC) curves). RESULTS: Fifty important
      variables, whose average importance scores were highest and whose error rates
      were lowest, were selected by random forest method. The importance scores of
      environmental variables (smoking, age and gender) were all listed at top 20,
      which were respectively 4.05, 3.12 and 1.16. After adjusting 3 environmental
      variables and false discovery rate (FDR), 6 SNPs were still significantly
      associated with lung cancer (FDR-P < 0.05). However, if traditional logistic
      regression analysis were directly applied, no significant SNPs were found. The
      likelihood testing result of AUC of the 2 ROC (one curve only included
      environmental variables and the other curve included environmental variables and
      SNPs) were 0.6491 +/- 0.0172 and 0.6811 +/- 0.0166 respectively; showed
      statistical significance of the association between the 6 SNPs and lung cancer
      (chi2 = 43.82, P = 3.6*10-11). CONCLUSION: Random forest analysis could first
      remove the turbulent SNPs and then make the analysis by logistic regression
      method. This could improve the testing efficacy, which is significantly better
      than single logistic regression analysis.

PMID- 23157893
TI  - Food consumption patterns and nutrition transition in South-East Asia.
AB  - OBJECTIVE: The present study was done to confirm the relationship between changes
      in food patterns and nutrition transition in three South-East Asian countries,
      namely the Philippines, Malaysia and Indonesia. DESIGN: This was a cross
      sectional study conducted between August 2008 and August 2009 using three
      methods: interviews, focus group discussions and analyses of government reports.
      SETTING: The study was conducted in rural and urban areas in Manila and Calabanga
      (Philippines), Selangor and Kuala Selangor (Malaysia), and Padang, Pariaman Tanah
      Datar and Limapuluh Kota (West Sumatra, Indonesia). SUBJECTS: Adults aged 18 to
      77 years. RESULTS: The results showed that Filipinos, Malaysians and Indonesians
      have retained many aspects of their traditional diets. In fact, most participants
      in the study considered Western-style and franchise fast foods as snack or
      recreational foods to be consumed once in a while only. However, a significant
      difference was noted between urban and rural areas in food varieties consumed.
      Participants in urban areas consumed more varieties of traditional foods owing to
      their availability and the participants' food purchasing power. Although
      traditional food patterns were maintained by most of the participants, more sugar
      and vegetable oils were consumed and added to the traditional recipes.
      CONCLUSIONS: The rapid nutrition transition in this region may be due, instead,
      to increasing food availability and food purchasing power, rather than to a shift
      in food preferences towards modern Western foods.

PMID- 23157894
TI  - Evaluation of the 'healthy start to pregnancy' early antenatal health promotion
      workshop:  a randomized controlled trial.
AB  - BACKGROUND: Pregnancy is an ideal time to encourage healthy lifestyles as most
      women access health services and are more receptive to health messages; however
      few effective interventions exist. The aim of this research was to deliver a low
      intensity, dietitian-led behavior change workshop at a Maternity Hospital to
      influence behaviors with demonstrated health outcomes. METHODS: Workshop
      effectiveness was evaluated using an RCT; 'usual care' women (n = 182) received a
      nutrition resource at their first antenatal visit and 'intervention' women also
      attended a one-hour 'Healthy Start to Pregnancy' workshop (n = 178). Dietary
      intake, physical activity levels, gestational weight gain knowledge, smoking
      cessation, and intention to breastfeed were assessed at service-entry and 12
      weeks later. Intention-to-treat (ITT) and per-protocol (PP) analyses examined
      change over time between groups. RESULTS: Approximately half (48.3%) the
      intervention women attended the workshop and overall response rate at time 2 was
      67.2%. Significantly more women in the intervention met pregnancy fruit
      guidelines at time 2 (+4.3%, p = 0.011) and had a clinically-relevant increase in
      physical activity (+27 minutes/week) compared with women who only received the
      resource (ITT). Women who attended the workshop increased their consumption of
      serves of fruit (+0.4 serves/day, p = 0.004), vegetables (+0.4 serves/day, p =
      0.006), met fruit guidelines (+11.9%, p < 0.001), had a higher diet quality score
      (p = 0.027) and clinically-relevant increases in physical activity (+21.3
      minutes/week) compared with those who only received the resource (PP).
      CONCLUSIONS: The Healthy Start to Pregnancy workshop attendance facilitates
      improvements in important health behaviors. Service changes and accessibility
      issues are required to assist women's workshop attendance to allow more women to
      benefit from the workshop's effects. TRIAL REGISTRATION: Australian New Zealand
      Clinical Trials Registry ACTRN12611000867998.

PMID- 23157896
TI  - [Discovery of potential DCD and factors influencing donation in China].

PMID- 23157895
TI  - Female partners of opioid-injecting men in the Republic of Georgia: an initial
      characterization.
AB  - BACKGROUND: HIV and Hepatitis C virus (HCV) infections are strongly related to
      injection drug use in the Republic of Georgia. Little information is available
      about HIV and HCV status, sexual risk, support for their partner, and risk for
      physical violence among the female partners of opioid-injecting men in the
      Republic of Georgia, many of whom may not be using drugs, yet may be at high risk
      of being infected with HIV and HCV from their drug-using partners. METHODS: In
      order to better understand the risks for females whose partners are injecting
      drugs, the present study conducted an initial investigation of the non-substance
      using female partners of 40 opioid-injecting men who were participating in a
      clinical trial examining the feasibility and efficacy of a 22-week comprehensive
      intervention that paired behavioral treatment with naltrexone. The 40 female
      partners were assessed at their male partners' study intake. RESULTS: The female
      sample was 32.3 years old (SD=6.7), 37 (93%) were married, with 15.5 years of
      education. A majority reported at least partial employment the majority of the
      time during the past 3 years, with only one woman reported being unemployed most
      of the time during the past 3 years. They self-reported they were 3% HIV-positive
      and 8% HCV-positive. Their HIV sex risk scores indicated a relatively low risk.
      However, only 4 (10%) women reported using a condom most of the time while having
      sex and 15 (38%) report not having had sex during the last 30 days. Experiences
      of interpersonal violence were common, with 42% reporting physical abuse by their
      partner during the last year and 48% reporting feeling unsafe in their current
      relationship. CONCLUSIONS: The alarmingly high rate of failure to use barrier
      protection methods, together with the high percentage who did not know their HIV
      and HCV status, suggest that it may be beneficial to include non-substance-using
      female partners in prevention programs along with their partners to reduce the
      risk of HIV and HCV spreading from the population of injection-drug-using males
      into the general population. [This secondary analysis study was funded by an
      international supplement to the parent randomized clinical trial "Treating the
      Partners of Drug Using Pregnant Women: Stage II (HOPE)". ]

PMID- 23157898
TI  - [Expert consensus: evaluation of coagulation function and intervention of
      coagulation disorders].

PMID- 23157897
TI  - [2012 NCCN guideline interpretation of the differentiated thyroid carcinoma].

PMID- 23157899
TI  - [Clinical observation on high intensity focused ultrasound combined with
      transcatheter arterial chemoembolization in the treatment of hepatocellular
      carcinoma].
AB  - OBJECTIVE: To study on the efficacy, prognosis and security of high-intensity
      focused ultrasound (HIFU) combined with transcatheter arterial chemoembolization
      (TACE) in the treatment of hepatocellular carcinoma (HCC). METHODS: Totally 72
      HCC patients treated by HIFU from December 2009 to January 2011 were divided into
      two groups according to treatment methods: 40 cases in HIFU group, 32 cases in
      TACE + HIFU treatment group (combined group). Then set up a control group include
      40 cases treated by only TACE in the same period (TACE group). The improvement of
      clinical symptoms, AFP, reduce rate of tumor volume, survival rate of 1 year
      after operation and postoperative complications in front and behind the treatment
      were analyzed. RESULTS: There was no significant statistical difference on the
      improvement of clinical symptoms in all these three groups (P > 0.05) after
      treatment for HCC. There is no significant statistical difference also on reduce
      rate of tumor volume and decrease rate of AFP in both HIFU group (35.0%, 41.4%)
      and TACE group (37.5%, 41.9%) (chi2 = 0.054, P = 0.816; chi2 = 0.002, P = 0.965).
      Both reduce rate of tumor volume (62.5%) and decrease rate of AFP (72.0%) in
      combined group were better than HIFU group (chi2 = 5.394, P = 0.020; chi2 =
      5.098, P = 0.024) and TACE group (37.5%, 41.9%) (chi2 = 4.448, P = 0.035; chi2 =
      5.062, P = 0.024). Kaplan-Meier survival curve showed that there was no
      significant statistical difference on short-term survival rate in the 3 groups.
      But the long-term survival rate of combined group was better than TACE group and
      HIFU group. CONCLUSION: TACE combined with HIFU is a effective, safe and
      noninvasive treatment method to HCC.

PMID- 23157900
TI  - [Impact of disease activity on postoperative recurrence and complications after
      bowel resection for Crohn's disease].
AB  - OBJECTIVE: To determine whether the perioperative disease activity is associated
      with recurrence and complications after bowel resection for Crohn's disease (CD).
      METHODS: Clinical data of patients underwent bowel resection for CD at the
      Nanjing General Hospital of Nanjing Military Command from January 2002 to January
      2011 was retrospectively analyzed. Postoperative recurrence and complications in
      patients with active disease were compared with those in patients with remission.
      RESULTS: A total of 90 patients underwent bowel resection for CD, active disease
      were seen in 43 patients at the time of surgery, while the rest 47 patients were
      in remission. The postoperative cumulative endoscopic recurrence rate was 8.5% at
      1 year, 27.7% at 2 years and 44.7% at 3 years in the patients with remission, and
      was 27.9% at 1 year, 37.2% at 2 years and 53.5% at 3 years in patients with
      active disease. Data indicated the endoscopic recurrence were statistically
      significant in the first year after surgery (chi2 = 4.605, P = 0.032).
      Additional, the postoperative complication rates in patients with remission
      (14.9%) was significantly lower than that in patients with active disease (51.2%)
      (chi2 = 6.979, P < 0.001). CONCLUSION: Patients with active disease at the time
      of surgery were encountered with early postoperative recurrence and increased
      complications after intestinal resection for CD.

PMID- 23157901
TI  - [The application of uncut Roux-en-Y esophagojejunostomy with distal jejunal pouch
      on behalf of the stomach surgery in the digestive tract reconstruction after
      total gastrectomy].
AB  - OBJECTIVE: To study the clinical value of uncut Roux-en-Y esophagojejunostomy
      with distal jejunal pouch on behalf of the stomach (URYAJP) surgery in the
      digestive tract reconstruction after total gastrectomy. METHODS: A retrospective
      analysis of radical resection of the whole stomach in 486 cases of gastric cancer
      patients, divided into the URYAJP group (n = 189), the P-loop Roux-en-Y behalf of
      the stomach surgery (PRY) group (n = 150) and pure Roux-en-Y reconstruction (RY)
      group (n = 147). Three groups were compared in patients with surgical
      reconstruction time, the occurrence of postoperative complications, the
      postoperative weight after 6, 12 and 24 months, the single meal food intake and
      prognostic nutritional index (PNI) and Visick points class situation after 12 and
      24 months. RESULTS: (1) The URYAJP group and RY group had no significant
      difference in digestive tract reconstruction time ((37 +/- 6) minutes and (38 +/-
      6) minutes respectively), but PRY group was significantly prolonged ((47 +/- 6)
      minutes, t = 7.52 and 6.54, P < 0.05). (2) In the comparison of the incidence of
      complications, URYAJP group has 2.1% rate of Roux stay syndrome (RSS) incidence,
      significantly less than PRY group (21.3%) and RY group (19.7%) (chi2 = 14.84, P <
      0.05). (3) In the comparison the postoperative nutritional status, URYAJP group
      clear asset, showing the degree of ((3.1 +/- 1.0) kg) weight loss after 12 months
      (t = 25.03 and 22.99, P < 0.05). And after 12, 24 months, a single meal eating
      reached the preoperative level is 94.8% and 96.9% in URYAJP group, while PRY
      group and RY group is less than 50% (chi(2) = 61.10, 69.17, 65.17 and 73.29, P <
      0.05). URYAJP Group reach the preoperative levels of PNI in 24 months after
      surgery, while PRY and RY group were still lower than per-operation (t = 106.97
      and 100.37, P < 0.05). (4) The Visick points class I-II postoperative 12 and 24
      months in URYAJP group were 92.7% and 93.8%, significantly better than group B
      and C (chi2 = 10.63, 14.19, 10.10 and 10.74, P < 0.05). CONCLUSIONS: URYAJP
      surgery give full play to maintain intestinal continuity, simple operation, and
      advantages of food storage bags, it can reduce the long-term postoperative
      complications, improve the nutritional status of patients and improve quality of
      life. It is worthy of promoting a way of gastrointestinal reconstruction.

PMID- 23157902
TI  - [A prospective randomized control clinical trial about clopidogrel combined with
      warfarin versus clopidogrel alone in the prevention of restenosis after femoral
      popliteal artery angioplasty].
AB  - OBJECTIVE: Using two antithrombotic treatment (clopidogrel vs. clopidogrel
      combined warfarin) strategies after femoral-popliteal artery angioplasty
      prospectively, to evaluate which strategy is more effective for the restenosis
      prevention. METHODS: Totally 50 patients referred for endovascular treatment
      (including the percutaneous transluminal angioplasty (PTA) and stent
      implantation) of the superficial femoral artery and popliteal artery from January
      2008 to May 2009 were randomly divided into clopidogrel group (group A, 25 cases,
      30 limbs) and clopidogrel plus warfarin group (group B, 25 cases, 33 limbs)
      before operation. Clinical outcomes and restenosis rate of the target lesions
      were evaluated at 3, 6 and 12 months after operation. RESULTS: Totally 88
      patients were screened for participation in the study, 56 patients were included
      after the follow-up of 12 months. At 3 months, the rates of restenosis were 16.7%
      in group A and 18.2% in group B (chi2 = 0.025, P = 0.874). At 6 months, the
      accumulated restenosis rates were 36.7% in group A and 36.4% in group B (chi2 =
      0.001, P = 0.98). At 12 months, the accumulated restenosis rates were 53.3% in
      group A and 42.4% in group B (chi2 = 0.75, P = 0.387). Analysis for the critical
      limb ischemia sub-group showed that follow-up of 12 months, the accumulated
      restenosis rate was 8/10 in group A and 6/12 in group B (chi2 = 1.023, P =
      0.312). CONCLUSION: The clopidogrel alone treatment for PTA or PTA plus stent
      implantation of femoral popliteal artery has no statistically significant
      difference in comparison with the clopidogrel combined warfarin treatment in
      terms of the cumulative vascular restenosis rate at 3, 6, 12 months
      postoperatively.

PMID- 23157903
TI  - [Idiopathic thoracolumbar/lumbar scoliosis treated with anterior correction and
      interbody fusion with calcium phosphate cement].
AB  - OBJECTIVE: To investigate the clinical outcome and fusion rate in patients with
      idiopathic thoracolumbar/lumbar scoliosis treated with anterior correction and
      interbody fusion with calcium phosphate cement. METHODS: From October 2006 to
      March 2008, 24 cases undergoing anterior correction and interbody fusion with
      calcium phosphate cement were enrolled. All of them were female, with an age
      ranged from 12 to 25 years. The mean Cobb angle of main curve was 46 degrees  +/-
      5 degrees  (range, 40 degrees  - 56 degrees ) before surgery. During operation,
      the most proximal and distal disc spaces were filled with rib autograft, while
      the remaining levels were filled with calcium phosphate cement. The interbody
      fusion rate, coronal correction and sagittal profile reconstruction were
      evaluated respectively by using chi2 test and t test. RESULTS: Interbody fusion
      was performed in 103 levels, including 48 levels with rib autograft and 55 levels
      with calcium phosphate cement. The mean follow-up period was 23.8 months (range,
      12 - 33 months) in this series. At the follow-up of 6 months, fusion rate was
      found as 54.2% in the levels filled with rib autograft, while 50.9% in those
      filled with calcium phosphate cement. Solid fusion of the whole instrumented area
      was achieved in all cases with a minimum one-year follow-up. No instrumentation
      related complications occurred. The correction rate of main curve was on an
      average of 76% +/- 11% after surgery. A significant difference was found between
      preoperative and immediate postoperative value in terms of the main curve
      magnitude (46 degrees  +/- 5 degrees  vs. 14 degrees  +/- 5 degrees , t = -26.95,
      P < 0.05). The correction loss of the main curve was -5.1 degrees  - 10.4 degrees
      at the final follow-up. The coronal balance and lower instrumented vertebra
      tilting were significantly improved after operation. The thoracolumbar kyphosis
      was significantly reduced postoperatively (t = 3.11, P < 0.05). CONCLUSION:
      Satisfactory bone fusion and correction maintenance can be achieved in idiopathic
      thoracolumbar/lumbar scoliosis treated by anterior instrumentation combined with
      interbody fusion using calcium phosphate cement.

PMID- 23157904
TI  - [The efficacy of one-stage posterior correction surgery for scoliotic patients
      with little symptomatic syringomyelia].
AB  - OBJECTIVE: To investigate the safety and effectiveness of one-stage posterior
      correction of scoliosis associated with little symptomatic syringomyelia.
      METHODS: A total of 19 cases diagnosed as scoliosis with little symptomatic
      syringomyelia between January 2003 and November 2010 were included in this study
      (study group), the patients underwent one-stage posterior correction and
      instrumentation without neurosurgery for the syringomyelia. At the same time, 9
      cases with severe symptomatic syringomyelia were included as the control group,
      the patients underwent neurosurgery before scoliosis correction, including
      suboccipital decompression and syrinx shunting. All patients underwent posterior
      pedicle screw or screw-hook hybrid instrumentation. The preoperative,
      postoperative and the last follow-up of the Cobb angle of the coronal main curve
      and thoracic kyphosis were measured. Also, the preoperative and postoperative of
      the apical vertebra translation, apical vertebra rotation and trunk shift were
      measured by the same person. The perioperative and the last follow-up
      complications of neurological injury were recorded. The surgical outcome and
      postoperative complications between the 2 groups were compared with the t student
      and chi-square statistics methods. RESULTS: There were no significant differences
      in gender, age, the location, length and diameter of the syringomyelia of the 2
      groups (P > 0.05). The follow-up period ranged from 6 to 45 months, with a mean
      of 28.6 months. The average preoperative Cobb angles of coronal main curves of
      the 2 groups were 71 degrees  +/- 23 degrees  and 68 degrees  +/- 19 degrees ,
      the postoperative Cobb angles were 27 degrees  +/- 20 degrees  and 25 degrees  +/
      16 degrees , and the last follow-up Cobb angles were 29 degrees  +/- 17 degrees 
      and 32 degrees  +/- 20 degrees . The coronal correction rate was 66% +/- 19% in
      the study group and 65% +/- 21% in the control group (t = 0.136, P = 0.893).
      There was no significant difference at the last follow-up(t = 0.210, P = 0.837).
      The average preoperative Cobb angles of thoracic kyphosis of the 2 groups were 35
      degrees  +/- 18 degrees  and 32 degrees  +/- 19 degrees , the postoperative Cobb
      angles were 25 degrees  +/- 10 degrees  and 23 degrees  +/- 9 degrees , and the
      last follow-up Cobb angles were 24 degrees  +/- 4 degrees  and 28 degrees  +/- 8
      degrees . The mean sagittal correction rate of the 2 groups were 50% +/- 58% and
      57% +/- 53% (t = -0.303, P = 0.764). There was also no significant difference at
      the last follow-up time (t = 0.769, P = 0.490). There were no significant
      difference, in terms of the postoperative of the apical vertebra translation,
      apical vertebra rotation and trunk shift between the 2 groups (P > 0.05). One
      case in the study group complicated with a pedicle screw breaking the anterior
      cortex of the vertebra and one in the control group complicated with a hook
      loosening, postoperatively. At the last follow-up time, the neurological symptoms
      of the 2 groups got no aggravating. CONCLUSION: One-stage posterior correction of
      scoliosis associated with little symptomatic syringomyelia may be effective and
      safe.

PMID- 23157905
TI  - [Comparison of stability of sacroiliac screws in the treatment of bilateral
      sacral fractures in a finite element model].
AB  - OBJECTIVE: To compare the stability of sacroiliac screws fixation for the
      treatment of bilateral vertical sacral fractures to provide reference for clinic
      application. METHODS: A finite element model of Tile C pelvic ring injury
      (bilateral type Denis II fracture of sacrum) was produced. The bilateral sacral
      fractures were fixed with sacroiliac screws in 4 types of models respectively:
      two bidirectional sacroiliac screws fixation in the S1 segment, two bidirectional
      sacroiliac screws fixation in the S2 segment, one sacroiliac screw fixation in
      the S1 segment and one sacroiliac screw fixation in the S2 segment, two
      bidirectional sacroiliac screws fixation in S1 and S2 segments respectively. By
      the ABAQUS 6.9.1 software, in the case of standing on both feet, 600 N vertical
      load was imitated to be imposed to the superior surface of the sacrum and
      downward translation and backward angle displacement of the middle part of the
      sacral superior surface and everted angle displacement of the top of iliac bones
      were extracted for analysis. The stability of sacroiliac screws fixation was
      compared according to the principle of the better stability the smaller
      displacement. RESULTS: The stability of 2 bidirectional sacroiliac screws
      fixation in S1 and S2 segments respectively was markedly superior to that of 2
      bidirectional sacroiliac screws fixation in S1 or S2 segment and was also
      markedly superior to that of one sacroiliac screw fixation in S1 segment and one
      sacroiliac screw fixation in S2 segment. The vertical and everted stability (the
      downward translation: 0.531 mm; the everted angle displacement: 0.156 degrees 
      (left side), 0.163 degrees  (right side)) of sacroiliac screws fixation in two
      bidirectional sacroiliac screws fixation in the S2 segment was superior to that
      of two bidirectional sacroiliac screws fixation in the S1 segment (the downward
      translation: 0.673 mm; the everted angle displacement: 0.200 degrees  (left
      side), 0.232 degrees  (right side)). The rotational stability of two
      bidirectional sacroiliac screws fixation in the S1 segment (the backward angle
      displacement: 0.269 degrees ) was superior to that of two bidirectional
      sacroiliac screws fixation in the S2 segment (the backward angle displacement:
      0.287 degrees ). Moreover, the rotational stability of one sacroiliac screw
      fixation in the S1 segment and one sacroiliac screw fixation in the S2 segment
      was inferior to that of two bidirectional sacroiliac screws fixation in the S1
      segment or two bidirectional sacroiliac screws fixation in the S2 segment, and
      the vertical and everted stability of one sacroiliac screw fixation in the S1
      segment and one sacroiliac screw fixation in the S2 segment was between that of
      two bidirectional sacroiliac screws fixation in the S1 segment and two
      bidirectional sacroiliac screws fixation in the S2 segment. CONCLUSIONS: Two
      bidirectional sacroiliac screws fixation in S1 and S2 segments respectively is
      recommended to be utilized for fixing bilateral sacral fractures of Tile C pelvic
      ring injury as far as possible. It is suggested to choose sacral segments in
      which sacroiliac screws fixed according to vertical, rotational and everted
      stability degree of sacral fractures.

PMID- 23157906
TI  - [Surgical treatment of large or giant cavernous sinus hemangiomas via epidural
      approach].
AB  - OBJECTIVE: To summarize the curative effect of surgically treated large or giant
      cavernous sinus hemangiomas (CSH) via epidural approach. METHODS: From June 1999
      to June 2011, 19 cases of CSH including 15 female and 4 male patients, ranging
      from 26 to 70 years (mean 45.3 years) were retrospectively reviewed.
      Ptosis/ocular motility disorders (10 cases), headache/ophthalmalgia (7 cases),
      decreased visual acuity (7 cases) and facial hyperesthesia (4 cases) were the
      most common presenting complaints. The epidural approach was taken and the tumor
      dissection was performed at the interval between trochlear nerve and ophthalmic
      nerve and the interval between ophthalmic nerve and maxillary nerve. The curative
      effect was followed up regularly. RESULTS: Gross total resection was attained in
      13 cases, near-total resection in 4 cases, subtotal resection in 1 case and
      partial resection in 1 case. The follow-up period was between 6-144 months (mean
      41.5 months). The results of last follow-up were as follows: among the 10
      patients with ptosis/ocular motility disorders, complete remission was achieved
      in 5, improvement in 2, no change in 2 and lost follow-up in 1. Facial
      hypoesthesia symptom got complete remission in 2 patients and partial remission
      in the other 2 patients. The other symptoms mentioned above were all relieved.
      One patient got complication with impairment of vision and ocular motility
      disorders. CONCLUSIONS: Combined with skilled skull base techniques, surgical
      treatment of large or giant CSH via epidural approach is an effective method and
      the preservation of cranial nerves could be attained to an acceptable level.

PMID- 23157907
TI  - [Clinicopathological significance of the expression of carbonic anhydrase II in
      human pancreatic invasive ductal cancer].
AB  - OBJECTIVE: To study the clinicopathological significance of the expression of
      carbonic anhydrase (CA)II protein and mRNA in primary invasive ductal cancer
      (IDC) of human pancreas. METHODS: The expression of CAII protein in 33 paired
      paraffin embedded IDC specimens of the pancreas and paired adjacent non-cancerous
      pancreatic tissues was detected by immunohistochemistry. Western blot and reverse
      transcription polymerase chain reaction (RT-PCR) were used to examine the
      expression of CAII protein and mRNA level in 12 paired fresh IDC specimens of the
      pancreas and adjuvant non-cancerous pancreatic tissues. The relationship between
      the protein expression and clinicopathological features was analyzed. RESULTS:
      Overexpression of CAII protein was shown in 11 cases of pancreatic IDC tissues
      (33.3%, 11/33), which was much lower than that in paired non-cancerous pancreatic
      tissues (72.7%, t = 6.275, P = 0.000). The expression of CAII protein had no
      correlation with tumor position (chi2 = 0.992, P = 0.319), differentiation (chi2
      = 0.866, P = 0.352), TNM stage (chi2 = 1.210, P = 0.271) and Lymph node
      metastasis (chi2 = 0.798, P = 0.372), but had bordering statistic sig with the
      prognosis of the patients (chi2 = 3.233, P = 0.072). The median survival time in
      the patients with high expression of CAII protein was 540 days, while that in the
      patients with low expression was 320 days. The expression of CAII protein and
      mRNA was lower in IDC than that in paired non-cancerous pancreatic tissues
      detected by Western blot and RT-PCR respectively (t = 3.399, P = 0.006; t =
      2.281, P = 0.043). CONCLUSION: CAII is down regulated in pancreatic IDC and might
      be relative with the prognosis.

PMID- 23157908
TI  - [Gene therapy study on bladder cancer with recombinant adenoviral vector carrying
      LRIG1 gene driven by Survivin promoter].
AB  - OBJECTIVE: To investigate the treatment efficiency and mechanism of recombinant
      adenoviral vector carrying LRIG1 gene driven by Survivin promoter for bladder
      cancer. METHODS: Human bladder cancer cell line BIU87 and immortalized human
      bladder epithelial cells SV-HUC-1 were infected with Ad-Surp-LRIG1 and Ad-LRIG,
      respectively. The selective infection efficiency of Ad-Surp-LRIG1 and Ad-LRIG
      were evaluated by checking the expression of epidermal growth factor receptor
      (EGFR). The MTT method was used to test cell growth inhibition ratio of Ad-Surp
      LRIG1 and Ad-LRIG. Heterotransplanted models of human bladder cancer cell line
      BIU87 cells in nude mice were established. The mice were randomly divided into 3
      groups during the experiment: Ad-Surp-LRIG1 group received viral supernatant
      solution of Ad-Surp-LRIG1 by tail vein injection; Ad-LRIG group received viral
      supernatant solution of Ad-LRIG by tail vein injection; and PBS group received
      phosphate buffer solution (PBS). The growth of tumors were observed and the
      growth curve was mapped. The expression of LRIG1 and EGFR were examined by
      reverse transcription PCR (RT-PCR). RESULTS: When Multiplicity of infection was
      25, the transfection efficiency of Ad-Surp-LRIG1 was 74.56% in BIU87 cells and 0
      in SV-HUC-1 cells (chi2 = 58.640, P = 0.000), while the transfection efficiency
      of Ad-LRIG was 68.27% in BIU87 cells and 72.52% in SV-HUC-1 cells (chi2 = 0.075,
      P = 0.784). The transfection efficiency difference of Ad-Surp-LRIG1 and Ad-LRIG
      in BIU87 cells was not statistically significant (chi2 = 0.016, P = 0.898).
      Compared with PBS, Ad-Surp-LRIG1 and Ad-LRIG1 could inhibit BIU87 cell growth,
      the difference was significant in 4 days after transfection (F = 15.960, P =
      0.000). There was not significant difference in cell growth rate of Ad-Surp-LRIG1
      group and Ad-LRIG1 group. The tumor growth rate in Ad-Surp-LRIG1 group was slower
      than that in the other 2 groups. The tumor quality in Ad-Surp-LRIG1 was lighter
      than that in the other two groups, the differences were statistically significant
      (F = 97.860, P = 0.000), the quality difference in Ad-LRIG1 group and PBS group
      was not statistically significant difference (t = 1.73, P = 0.06). Compared with
      Ad-LRIG1 group and PBS group, the mRNA expression of LRIG1 was obviously up
      regulated and that of EGFR was down-regulated in Ad-Surp-LRIG1 group (P < 0.01).
      CONCLUSIONS: The recombinant adenoviral vector of Ad-Surp-LRIG1 could selectively
      transfected BIU87 cells, which could inhibit significantly the growth of bladder
      cancer in vivo and in vitro, the mechanism may be partly LRIG1 can downgrade the
      expression of EGFR.

PMID- 23157909
TI  - [Screen and identification of the relative protein expressed in the acute
      tractive spinal cord injury in rats].
AB  - OBJECTIVE: To screen and identify the relative protein expressed in the acute
      tractive spinal cord injury (TSCI) in rats. METHODS: Ten adult Sprague Dawley
      rats were randomly divided into Sham group and TSCI group, 5 rats in each group.
      Rats from Sham group and TSCI group at 1 day after surgery were sacrificed for
      harvesting T13-L2 spinal tissue specimens. The extraction and quantitation of
      protein in the spinal tissue was finished firstly. Proteins from spinal tissue
      were separated by two-dimensional electrophoresis (2-DE) and identified by mass
      spectrometry (MS). The different expression map was established in each group,
      and proteins express differently was determined by comparing the level of each
      spot with gel imaging software and manually. Proteins were identified by High
      performance liquid chromatography-electrospray tandem (NanoUPLC-ESI-MS/MS) and
      peptide sequence tag with tandem MS combining with database respectively. After
      that, the function of these identified proteins was known and classified.
      RESULTS: There were 22 differential protein expression spots were found between
      Sham group and TSCI group. Among them, 18 spots were up-regulated and 4 were down
      regulated. 4 differential protein expression spots were newly found in TSCI
      group. Sixteen significant proteins were identified by NanoUPLC-ESI-MS/MS. Four
      kind of proteins were related to apoptosis, 3 in nerve signal transduction and 6
      in metabolism, respectively. Unnamed proteins were 3. CONCLUSIONS: The
      differential expression proteins were found between Sham group and TSCI group.
      These identified proteins may play important role in the process of injury and
      recovery through transduction nerve signal, regulating nerve cells apoptosis and
      metabolism.

PMID- 23157910
TI  - [The effects of insulin-like growth factor 1 and transforming growth factor beta
      3 at various concentration on tenocyte survival and collagen formation].
AB  - OBJECTIVE: To optimize the culture media by adding the growth factors required to
      maintain tenocytes survival and promote their differentiation without fetal
      bovine serum (FBS) supplementation, in order for the approach to be used for any
      future tendon tissue engineering. METHODS: The human tenocytes were cultured in
      alpha-MEM media by adding FBS at various concentrations and supplementing both
      insulin-like growth factor 1 (IGF-1) and transforming growth factor beta-3
      (TGFbeta-3). A number of growth factors were selected that could support
      tenocytes expansion at reduced differentiated state with the minimum FBS. By
      employing fractional factorial design, different treatment groups went through
      AlamarBlue(TM) tests to evaluate the cell number growth whilst collagen
      quantification by real time RT-PCR technique and tenocyte differentiation were
      also studied. RESULTS: The tenocytes cultured for 14 days with 0% FBS, 50 ng/ml
      IGF-1 and 10 ng/ml TGFbeta-3 maintained survival over 14 days, the Cell count
      were 6228.68 +/- 43.87. They were higher than the other experimental groups, but
      less than 10% FBS control group (13 576.74 +/- 286.75, t = 41.29, P < 0.05). The
      tenocytes cultured in the treated group also showed enhanced collagen synthesis
      ((0.322 +/- 0.003) ng, t = 4.13 - 5.93, P < 0.05). CONCLUSION: These findings
      have shown for the first time that human tenocytes could be maintained survival
      for a long period of time in the culture media without FBS, having this approach
      a suitable one for tendon tissue engineering.

PMID- 23157911
TI  - Collaborative software for traditional and translational research.
AB  - Biomedical research has entered a period of renewed vigor with the introduction
      and rapid development of genomic technologies and next-generation sequencing
      methods. This research paradigm produces extremely large datasets that are both
      difficult to store and challenging to mine for relevant data. Additionally, the
      thorough exploration of such datasets requires more resources, personnel, and
      multidisciplinary expertise to properly analyze and interpret the data. As a
      result, modern biomedical research practices are increasingly designed to include
      multi-laboratory collaborations that effectively distribute the scientific
      workload and expand the pool of expertise within a project. The scope of
      biomedical research is further complicated by increased efforts in translational
      research, which mandates the translation of basic laboratory research results
      into the human medical application space, adding to the complexity of potential
      collaborations. This increase in multidisciplinary, multi-laboratory, and
      biomedical translational research identifies a specific need for formalized
      collaboration practices and software applications that support such efforts.
      Here, we describe formal technological requirements for such efforts and we
      review several software solutions that can effectively improve the organization,
      communication, and formalization of collaborations in biomedical research today.

PMID- 23157912
TI  - Interferon gamma assays in the diagnosis of tuberculosis infection in psoriasis
      patients who are candidates for biologic therapies.
AB  - Although there is no doubt that biologic agents are an effective alternative for
      the treatment of moderate and severe psoriasis, anti-tumor necrosis factor alpha
      therapy has been associated with reactivation of latent tuberculosis infection.
      Tuberculin skin testing (TST) is used to diagnose tuberculosis infection but it
      has low specificity in patients who have received the Mycobacterium bovis BCG
      vaccine and low sensitivity in patients with altered cell-mediated immunity. In
      vitro assays based on the detection of interferon gamma released by T cells
      stimulated by specific Mycobacterium tuberculosis antigens have emerged as an
      option for the diagnosis of tuberculosis infection. The results to date show that
      they are a viable alternative to TST thanks to their higher specificity and
      sensitivity. Furthermore, these assays are also proving to have high negative
      predictive value, meaning that we might be able to use them without TST in the
      short to medium term.

PMID- 23157913
TI  - Cardiovascular risk and psoriasis: the role of biologic therapy.
AB  - One of the most clinically important aspects of recent advances in our
      understanding of psoriasis has been the detection of an association between this
      disease and an increased prevalence of cardiovascular risk factors. This increase
      in prevalence is, in turn, linked to a greater risk of morbidity and mortality
      related to acute myocardial infarction, cerebrovascular accident, and peripheral
      arterial disease. The chronic systemic inflammation present in psoriasis could
      explain why moderate to severe psoriasis is an independent risk factor for
      cardiovascular disease. The introduction of biologic therapies has greatly
      improved the expectations of treatment as well as the long-term control of
      psoriasis, and there is epidemiological evidence that these therapies may lower
      cardiovascular risk in psoriasis as they do in rheumatoid arthritis. Caution
      should, however, be exercised when prescribing biologic drugs in this setting,
      because adverse effects have been reported in association with the use of tumor
      necrosis factor inhibitors in patients with advanced congestive heart failure.
      Furthermore, a numerical imbalance (without statistical significance) between the
      groups receiving the biologic drug and the placebo groups was recently observed
      in the incidence of major cardiovascular events (nonfatal myocardial infarction
      and cerebrovascular accident and cardiovascular death) during the controlled
      periods of clinical trials of briakinumab and ustekinumab, 2 monoclonal
      antibodies that target the p40 subunit shared by IL-12 and IL-23. We review the
      current scientific evidence on this topic.

PMID- 23157914
TI  - Photodynamic therapy as a response to the challenge of treating actinic keratosis
      in the eyelid area.

PMID- 23157915
TI  - Mobile nodules on the legs.

PMID- 23157916
TI  - Occupational contact dermatitis in the wind energy industry.
AB  - BACKGROUND AND OBJECTIVES: In 2010, wind energy coverage in Spain increased by
      16%, making the country the world's fourth largest producer in a fast-developing
      industry that is also a source of employment. Occupational skin diseases in this
      field have received little attention. The present study aims to describe the main
      characteristics of skin diseases affecting workers in the wind energy industry
      and the allergens involved. MATERIAL AND METHODS: We performed a descriptive,
      observational study of workers from the wind energy industry with suspected
      contact dermatitis who were referred to the occupational dermatology clinic of
      the National School of Occupational Medicine (Escuela Nacional de Medicina del
      Trabajo) between 2009 and 2011. We took both a clinical history and an
      occupational history, and patients underwent a physical examination and patch
      testing with the materials used in their work. RESULTS: We studied 10 workers (8
      men, 2 women), with a mean age of 33.7 years. The main finding was dermatitis,
      which affected the face, eyelids, forearms, and hands. Sensitization to epoxy
      resins was detected in 4 workers, 1 of whom was also sensitized to epoxy curing
      agents. One worker was sensitized to bisphenol F resin but had a negative result
      with epoxy resin from the standard series. In the 5 remaining cases, the final
      diagnosis was irritant contact dermatitis due to fiberglass. CONCLUSIONS:
      Occupational skin diseases are increasingly common in the wind energy industry.
      The main allergens are epoxy resins. Fiberglass tends to produce irritation.

PMID- 23157917
TI  - Cultural practices in immigrant populations and their relevance to dermatology.

PMID- 23157919
TI  - Clinical and therapeutic evaluation of patients with moderate to severe psoriasis
      in Spain: the secuence study.
AB  - BACKGROUND: Evaluation of disease severity is considered essential in the optimal
      management of psoriasis. OBJECTIVES: To describe the clinical characteristics and
      therapeutic profile of patients with moderate to severe psoriasis in Spain and to
      assess the impact of the disease on the patients' quality of life. MATERIALS AND
      METHODS: This was an observational, cross-sectional study carried out in 90
      dermatology units in Spain in 2009. We included 442 patients diagnosed with
      moderate to severe psoriasis who had started treatment with systemic agents,
      phototherapy, and/or topical treatments between 2004 and 2006. RESULTS: More
      severe psoriasis was significantly associated with the following: longer disease
      duration; higher prevalence of concomitant disease; greater involvement of the
      nails, scalp, flexures, palms, and soles; and poorer quality of life. In the 5
      years before the start of the study, 68% of the patients had received
      conventional systemic treatments, 39.1% biologic agents, and 22.3% phototherapy.
      At present, 57.5% of the patients are being treated with biologic agents, 32.6%
      with conventional systemic treatments, and 11% with phototherapy. CONCLUSIONS:
      Severity of psoriasis was associated with a marked impact on quality of life.
      Regardless of disease severity, psychiatric comorbidity was the strongest
      predictor of poor quality of life. On average, patients had received other
      treatments, such as conventional systemic treatments or phototherapy, for more
      than 2 years before switching to biologic agents for the first time.

PMID- 23157918
TI  - Allergic contact dermatitis to fragrances. Part 1.
AB  - Fragrances are a large group of substances and the second most common cause of
      allergic contact dermatitis in Spain. These potential allergens are extremely
      common and the general population is subject to continuous exposure on a daily
      basis. While the fragrance markers included in the current Spanish standard patch
      test series are good, there is room for improvement. New markers that have
      emerged in recent years have proven to be of value in standard series used in
      other countries. Diagnosing fragrance allergy has taken on even greater
      importance since the European Union added 26 fragrances to its list of mandatory
      ingredients to be specified on product labels. The aim of this review is to
      provide an update on allergic contact dermatitis to fragrances. We examine the
      main sources of exposure and clinical manifestations of this condition and
      propose a diagnostic and treatment protocol.

PMID- 23157920
TI  - What works and why? Evaluation of a community nutrition programme in Kenya.
AB  - OBJECTIVE: To investigate the nutritional impact of a community-based programme
      that focused on social cohesion and action. DESIGN: The change in nutritional
      status of children aged 12-60 months was examined over a period of 3 years in
      Makueni District in Eastern Province of Kenya in six communities in which an
      intervention programme of Participatory Learning and Action was introduced and in
      ten communities in which only basic preparations were made but no intervention
      was started. SETTING: The intervention was part of the Government of Kenya
      Community Based Nutrition Programme and was supported by the Government of
      Denmark. SUBJECTS: Children aged 12-60 months. RESULTS: Among communities without
      intervention there were similar levels of underweight (mean Z-score: -1.63 v. 
      1.50 (NS); % with Z-score<-2: 36.6% v. 34.5% (NS)) and stunting (mean Z-score: 
      2.0 v. -1.99 (NS); % with Z-score<-2: 44.3% and 47.4% (NS)) at baseline and after
      3 years. By contrast, among communities who had received interventions, there
      were significant improvements after 3 years in the levels of underweight (mean Z
      score: -1.66 v. -1.37 (P<0.02); % with Z-score <-2: 42.9% v. 31.4% (P<0.035)) and
      stunting (mean Z-score: -2.05 v. -1.59 (P<0.05); % with Z-score<-2: 52.7% v.
      39.7% (P<0.02)). CONCLUSIONS: The results indicate considerable potential for
      using Participatory Learning and Action as a community-based approach to
      effectively address child undernutrition. It is suggested that these
      interventions are developed, implemented and evaluated more widely as a mean of
      tackling childhood undernutrition and improving child survival and development.

PMID- 23157921
TI  - A duty of care.
AB  - Mass production of PhD training compromises graduate quality. As PhD quality
      becomes more stratified, industry will increasingly turn to quality-branded
      institutions and programs when distinguishing among job candidates.

PMID- 23157922
TI  - Ischemia Index to predict post coronary artery bypass graft change in left
      ventricular ejection fraction.
AB  - INTRODUCTION: Both myocardial necrosis and ischemia can decrease the left
      ventricular ejection fraction (LVEF). An accurate estimate of the relative
      contributions of these irreversible and potentially reversible factors could lead
      to better decisions regarding the risk and benefit of coronary artery bypass
      grafting (CABG). The value of an Ischemia Index calculated by subtracting the ECG
      estimated infarction dependent LVEF from the measured LVEF to predict post
      operative improvement of LVEF was studied in 55 patients with LVEF <40% before
      CABG. Patients were grouped according to absence or presence of other coexisting
      ECG confounders. RESULTS: No significant (p=0.083) relationship was found between
      the Ischemia Index and the improvement in LVEF after CABG in the overall
      population, but a strong trend was present in the patients with ECGs without
      confounding QRS changes (p=0.056). CONCLUSION: These results suggest a positive
      relationship between the Ischemia Index and improvement of LVEF after CABG in
      patients without electrocardiographic confounders, but a prospective study using
      a larger sample is needed.

PMID- 23157923
TI  - Care planning and adherence to diabetes process guidelines: medicare data
      analysis.
AB  - OBJECTIVE: To test the association, in patients with a diagnosis of diabetes I
      and II, between having or not having a care plan, (i.e. General Practice
      Management Plans (GPMPs),Team Care Arrangements (TCAs)), and having the
      recommended number of biochemical checks according to the diabetes Annual Cycle
      of Care guideline. The checks comprised HbA1c, HDL cholesterol and urinary
      microalbumin. METHODS: Chi-square analysis of retrospective group data obtained
      from the Medicare database (from 'billing' patterns only). RESULTS: The creation
      of GPMPs was associated with general practitioners (GPs) requesting checks for
      HbA1c (59.7%), HDL cholesterol (36.9%) and microalbumin (50.8%) for diabetes
      patients in accordance with guideline recommendations. Although the introduction
      of multidisciplinary care via a TCA was associated with an increase in the
      frequency of HbA1c checks (61.3%) in accordance with the guidelines, there was a
      reduction in the number of HDL cholesterol (23.7%) and microalbumin (36.8%)
      checks. The group with no care plans had the lowest association with HbA1c
      (47.8%), HDL cholesterol (19.7%) and microalbumin (29.3%) checks that met
      guideline requirements for diabetes. CONCLUSIONS: The use of GPMPs showed strong
      association with increased testing of process measures that met guideline
      requirements for diabetes. Further research is needed to understand the value and
      benefits of TCAs in promoting adherence to diabetes guidelines.

PMID- 23157924
TI  - Aqueous ionic liquid based ultrasonic assisted extraction of eight ginsenosides
      from ginseng root.
AB  - We developed an aqueous ionic liquid based ultrasonic assisted extraction (ILUAE)
      method for the extraction of the eight ginsenosides (ginsenoside-Rg1, -Re, -Rf, 
      Rb1, -Rc, -Rb2, -Rb3 and -Rd) from ginseng root. A series of l-alkyl-3
      methylimidazolium ionic liquids differing in composition of anions and cations
      were evaluated for extraction efficiency. The results indicated that the ILUAE
      method has a remarkable ability to improve the extraction efficiency of
      ginsenosides. In addition, the ILUAE procedure was also optimized on some
      ultrasonic parameters, such as the IL concentration, solvent to solid ratio and
      extraction time. Under these optimal conditions (e.g., with 0.3M [C(3)MIM]Br,
      solvent to solid ratio of 10:1 and extraction time of 20min), this approach
      gained the highest extraction yields of total ginsenosides 17.81+/-0.47mg/g.
      Compared with the regular UAE, the proposed approach exhibited 3.16 times higher
      efficiency and 33% shorter extraction time, which indicated that ILUAE has a
      broad prospect for sample preparation of medicinal plants.

PMID- 23157925
TI  - Matrix metalloprotease 9 promotes liver recovery from ischemia and reperfusion
      injury.
AB  - BACKGROUND: Matrix metalloprotease (MMP) 9 has been always considered as a
      destructor of extracellular matrix, promoting liver injury and metastasis of
      carcinoma. In this study, we investigated the role of MMP-9 in liver wound
      healing from ischemia and reperfusion injury (IRI). METHODS: MMP9-/- mice were
      used to establish partial hepatic IRI model. Serum alanine aminotransferase and
      hepatic cytokines (tumor necrosis factor alpha, interleukin [IL]-1beta, IL-10,
      and transforming growth factor beta [TGF-beta]) levels were analyzed after IRI.
      Hepatic stellate cells were isolated from wild-type mice to determine the effect
      of MMP-9 on TGF-beta activation. In addition, the effect of TGF-beta on liver
      wound healing from IRI was determined. RESULTS: Liver recovery from IRI was
      impaired in MMP9-/- mice, which was described as elevated serum alanine
      aminotransferase, hepatic tumor necrosis factor alpha, and IL-1beta levels.
      Meanwhile, TGF-beta-active protein level was decreased in the liver of MMP9-/-
      mice. In vitro test, the activation of TGF-beta was suppressed in the presence of
      anti-MMP-9 monoclonal antibody. TGF-beta treatment promoted liver recovery from
      IRI in MMP9-/- mice. CONCLUSIONS: MMP-9 promoted liver recovery from IRI by
      activating TGF-beta. Thus, MMP-9 plays dual roles (bad and good) in liver IRI,
      depending on the timing.

PMID- 23157926
TI  - A longitudinal study on the incidence of mortality of infectious diseases of
      commercial layer birds in Bangladesh.
AB  - A 20-month longitudinal field study was undertaken during the period from January
      2010 to August 2011 to determine the incidence of mortality due to infectious
      diseases affecting commercial layer birds in 8 upazilas (an administrative unit)
      of 5 different districts in Bangladesh. Diagnosis of different diseases was made
      based on the flock history, age of birds, clinical signs, characteristic gross
      and microscopic lesions, and isolation and identification of the organisms.
      During the study period, 4710 birds were found dead as a result of disease
      occurrence. The incidence rate (true incidence rate) of mortality for the study
      period was 0.0171 per bird-months at risk. The incidences of mortality of almost
      all the infectious diseases were significantly higher in rainy followed by summer
      seasons. Particularly, mortality rate of ND and FC was significantly higher in
      rainy and summer seasons compared to winter and autumn seasons. And higher
      mortality rate of IBD, salmonellosis, IB, colibacillosis and MD was found in
      rainy than other three seasons. The highest mortality was recorded in birds below
      8 weeks of age followed by birds aged 21 weeks and above. The mortality due to
      IBD was significantly higher (0.006) in the young birds (<8 weeks of age) than
      older birds. On the other hand, mortality rate of ND was significantly higher
      (0.003) in older birds (>8 weeks of age). Statistically no significant difference
      (p>0.05) was observed in the mortality rate of colibacillosis between different
      age groups. The proportional mortality due to infectious diseases was 54.2%
      (including single or mixed infections). Of the overall mortality, 13.4% was
      attributed to ND, 9.53% to IBD, 6.69% to MD, 4.33% to IB, 4.23% to salmonellosis,
      3.23% to FC, 3.31% to colibacillosis, 1.1% to aspergillosis and 45.8% to non
      infectious causes. The findings indicated that infectious diseases appear to be a
      major constraint of commercial layer birds in Bangladesh.

PMID- 23157927
TI  - Factors associated with epidemiology of Anaplasma platys in dogs in rural and
      urban areas of Minas Gerais State, Brazil.
AB  - This epidemiological survey of Anaplasma platys was carried out in rural and
      urban areas of three distinct regions of the State of Minas Gerais, Brazil. EDTA
      blood samples were collected during the dry season from dogs living on farms with
      an attempt to resample the same dogs in the subsequent rainy season. Samples were
      also taken from dogs in urban areas. DNA was extracted from blood samples for
      real time PCR. Risk factors, such as age, breed, sex, presence of ticks, and
      packed cell volume were analyzed. During the rainy season, the prevalence of
      infection by A. platys in dogs in the rural areas was significantly higher
      (13.9%) than that observed in dogs in the urban areas (5.1%). Dogs in the Nanuque
      region were 3.74 times (p=0.001) more likely to be real-time PCR positive than
      dogs in the other two studied regions. Dogs infested with ticks showed higher
      rates of positivity. The results showed that in rural areas of Minas Gerais A.
      platys infection is influenced by climatic conditions. In areas of higher
      temperature and higher humidity, transmission occurs during both the dry and
      rainy seasons, while in areas with lower temperature and humidity transmission
      occurs mainly during the dry season.

PMID- 23157928
TI  - Combined heart and liver transplantation: the Cleveland Clinic experience.
AB  - BACKGROUND: Combined heart-liver transplantation (CHLT) has been utilized as a
      life-saving procedure in those with end-stage cardiac and hepatic pathology.
      Techniques and outcomes of this procedure are varied. We sought to review the
      Cleveland Clinic experience with CHLT. METHODS: This study is a retrospective
      chart review of patients who received simultaneous heart and liver
      transplantation between January 2006 and December 2012. RESULTS: Five patients
      received CHLT. The mean age was 49 (+/- 20) years. All cardiac pathology was
      nonischemic cardiomyopathy, with a mean ejection fraction of 0.36 (+/- 0.13).
      Three of the 5 were on preoperative inotropic support, 1 of which required
      placement of a total artificial heart for support pretransplant. Liver pathology
      was amyloid in 1 patient and hepatitis C in the remaining 4. Mean Model for End
      Stage Liver Disease score was 17 (+/- 5), and mean Childs-Pugh score was 8 (+/-
      1). Survival, now at a mean of 38 (+/- 20) months remains 100%, with no cardiac
      or hepatic graft dysfunction or episodes of rejection. One hospital readmission
      was required for gastroenteritis at 15 months posttransplant. CONCLUSIONS: These
      results suggest that excellent outcomes can be achieved in this extremely sick
      cohort of patients, and add to the growing literature of perioperative management
      of CHLT recipients.

PMID- 23157929
TI  - Identification of provider characteristics influencing prescription of
      analgesics: a systematic literature review.
AB  - PURPOSE: Pain is a comorbid and aggravating symptom that in many conditions can
      be perceived differently and should therefore be managed accordingly. Numerous
      factors, both social and cultural, are thought to influence the analgesic
      prescription. However, elucidation of such areas is limited. We therefore
      conducted a systematic literature review to test the hypothesis that variations
      in provider characteristics predict the prescription of pain medication. METHODS:
      A MEDLINE and PsycINFO database search from 1960 to 2009 was conducted using the
      search terms of "pain" or "pain treatment" along with culture, ethnicity, race,
      minority, gender/sex, knowledge, attitudes, physician-patient relationship,
      stereotype, and physician practices. Twelve original research articles based on
      predefined inclusion criteria were identified and analyzed to test the hypothesis
      of provider characteristics influencing analgesics prescription. RESULTS: Of the
      12 studies, 11 were cross-sectional in design, and 10 used a survey instrument or
      clinical vignettes to measure different pain management responses. A randomized
      sampling methodology was used in 5 of the studies. The majority of providers were
      male (64.9% in 8 studies), white (73.5% in 5 studies), internal medicine
      physicians (37.4% in 11 studies), and located in the United States (75% across
      all 12 studies). Ten studies identified at least one provider characteristic that
      influenced prescription practices; age, level of experience, as well as sex were
      listed most frequently as contributing factors. The interplay of the sex of the
      provider and patient characteristics were found to be important variables in pain
      management. CONCLUSIONS: Our systematic review of existing literature highlights
      that provider's age, sex, experience, specialty, and the interplay between
      provider and patient characteristics are important variables in pain management.
      However, generalizations relating to these findings are limited by the
      heterogeneity of the studies and the paucity of literature in this field.

PMID- 23157930
TI  - The impact of social, structural and physical environmental factors on
      transitions into employment among people who inject drugs.
AB  - Despite growing awareness of the importance of context for the health of people
      who use drugs, studies examining labour market outcomes have rarely considered
      the role that physical, social and structural factors play in shaping labour
      market participation among drug users. Using discrete time event history
      analyses, we assessed associations between high-intensity substance use,
      individual drug use-related risk and features of inner-city drug use scenes with
      transitions into regular employment. Data were derived from a community-recruited
      cohort of people who inject drugs in Vancouver, Canada (n = 1579) spanning the
      period of May 1996-May 2005. Results demonstrate that systematic socio
      demographic differences in labour market outcomes in this context generally
      correspond to dimensions of demographic disadvantage. Additionally, in initial
      analyses, high-intensity substance use is negatively associated with transitions
      into employment. However, this negative association loses significance when
      indicators measuring exposure to physical, social and structural features of the
      broader risk environment are considered. These findings indicate that
      interventions designed to improve employment outcomes among drug users should
      address these social, structural and physical components of the risk environment
      as well as promote the cessation of drug use.

PMID- 23157931
TI  - Estimating Willingness-to-Pay for health insurance among rural poor in India by
      reference to Engel's law.
AB  - Community-Based Health Insurance (CBHI) (a.k.a. micro health insurance) is a
      contributory health insurance among rural poor in developing countries. As CBHI
      schemes typically function with no subsidy income, the schemes' expenditures
      cannot exceed their premium income. A good estimate of Willingness-To-Pay (WTP)
      among the target population affiliating on a voluntary basis is therefore
      essential for package design. Previous estimates of WTP reported materially and
      significantly different WTP levels across locations (even within one state),
      making it necessity to base estimates on household surveys. This is time
      consuming and expensive. This study seeks to identify a coherent anchor for local
      estimation of WTP without having to rely on household surveys in each CBHI
      implementation. Using data collected in 2008-2010 among rural poor households in
      six locations in India (total 7874 households), we found that in all locations
      WTP expressed as percentage of income decreases with household income. This
      reminds of Engel's law on food expenditures. We checked several possible anchors:
      overall income, discretionary income and food expenditures. We compared WTP
      expressed as percentage of these anchors, by calculating the Coefficient of
      Variation (for inter-community variation) and Concentration indices (for intra
      community variation). The Coefficient of variation was 0.36, 0.43 and 0.50 for
      WTP as percent of food expenditures, overall income and discretionary income,
      respectively. In all locations the concentration index for WTP as percentage of
      food expenditures was the lowest. Thus, food expenditures had the most consistent
      relationship with WTP within each location and across the six locations. These
      findings indicate that like food, health insurance is considered a necessity good
      even by people with very low income and no prior experience with health
      insurance. We conclude that the level of WTP could be estimated based on each
      community's food expenditures, and that this information can be obtained
      everywhere without having to conduct household surveys.

PMID- 23157932
TI  - Dynamic profile of health investment and the evolution of elderly health.
AB  - A considerable number of studies have sought to examine the determinants of
      elderly health. Nevertheless, few of them incorporate a life-course perspective
      to analyze the dynamics of transition for both health conditions and their
      predictors. We utilize a nationally representative longitudinal data set of 4007
      Taiwanese aged 60 or over and employ discrete-time duration models to investigate
      the association between annual mortality and its potential risk factors over a
      nearly twenty-year period (1989-2007). We place particular emphasis on the
      inherently dynamic character of Grossman's model, and specifically on how public
      and private health investment shape the personal health outcome over time. Our
      results support the hypothesis that depreciation rates depend on personal
      characteristics. In addition, we find that the dynamic profiles of both public
      and private health investment significantly influence the elderly mortality. An
      important implication of our study is that implementing universal health
      insurance and tobacco control programs are effective channels through which the
      government improves personal health.

PMID- 23157933
TI  - Usability testing and acceptance of an electronic medication inquiry system for
      CKD patients.

PMID- 23157934
TI  - Survival advantage of icodextrin peritoneal dialysis solution in a time-dependent
      model.

PMID- 23157935
TI  - Effects of sodium intake and diet on racial differences in urinary potassium
      excretion: results from the Dietary Approaches to Stop Hypertension (DASH)-Sodium
      trial.
AB  - BACKGROUND: We previously showed that African Americans excreted less urinary
      potassium than whites, even while consuming similar diets in the Dietary
      Approaches to Stop Hypertension (DASH) trial. We hypothesized that a low-sodium
      diet may eliminate these differences. STUDY DESIGN: Data from the DASH-Sodium
      randomized controlled feeding trial were analyzed. SETTING & PARTICIPANTS: 412
      adults with prehypertension or stage 1 hypertension. INTERVENTION: Random
      assignment to either a typical American "control" diet (1.7 g [43 mEq]
      potassium/2,100 kcal/d) or the DASH diet (4.1 g [105 mEq] potassium/2,100
      kcal/d). Within each diet, participants received 3 levels of sodium intake in
      random order for 30 days. OUTCOMES & MEASUREMENTS: 24-hour urine samples were
      analyzed at the end of each period. The primary outcome was urinary potassium
      excretion. RESULTS: On the DASH diet, African Americans consistently excreted
      significantly less urinary potassium (mean 24-hour urinary potassium excretion,
      2,594 +/- 961 mg [66 +/- 25 mEq]) than whites (3,412 +/- 1,016 mg [87 +/- 26
      mEq]) at the highest sodium level; adjusted (P < 0.001); this difference was not
      altered by sodium level (P = 0.6 comparing white to African American difference
      in urinary potassium excretion on high- vs low-sodium diet). In contrast, there
      was a smaller but significant white-African American difference in mean daily
      urinary potassium excretion in participants fed the control/high-sodium diet that
      was not present in the control/low-sodium diet (adjusted differences of 281 mg [7
      mEq]/d vs 20 mg [0.5 mEq]/d, respectively; P = 0.007). Significant interactions
      were found between race and diet (P < 0.001) and between race and sodium (P =
      0.02). LIMITATIONS: Single rather than multiple urine collections were available
      at each time. Lack of stool potassium and sweat potassium values. CONCLUSIONS:
      Racial differences in urinary potassium excretion depend on sodium intake and
      diet. Our results may help explain the previously documented large variability in
      urinary potassium excretion.

PMID- 23157936
TI  - Use of fondaparinux for circuit patency in hemodialysis patients.

PMID- 23157938
TI  - Fistula First Breakthrough Initiative (FFBI): lessons about arteriovenous fistula
      prevalence goals.

PMID- 23157939
TI  - Abdominal compartment syndrome and acute kidney injury due to excessive auto
      positive end-expiratory pressure.
AB  - Abdominal compartment syndrome is an under-recognized cause of acute kidney
      injury in critically ill patients. We report a case of a patient with severe
      obstructive lung disease who, while intubated for respiratory failure, developed
      abdominal compartment syndrome and oliguric acute kidney injury due to air
      trapping and excessive auto-positive end-expiratory pressure (auto-PEEP; also
      known as intrinsic PEEP). When chemical paralysis was initiated and the auto-PEEP
      resolved, the patient's intra-abdominal hypertension rapidly improved and kidney
      function recovered immediately. Abdominal compartment syndrome secondary to
      excessive auto-PEEP appears to be unreported in the literature; however, any
      process that significantly increases intrathoracic pressure conceivably could
      cause increased pressure to be transmitted to the abdominal compartment,
      resulting in organ failure. Patients undergoing mechanical ventilation, which
      puts them at risk of airflow obstruction and the development of intra-abdominal
      hypertension, should be evaluated for air-trapping and excessive auto-PEEP.

PMID- 23157937
TI  - Effect of early initiation of dialysis on cardiac structure and function: results
      from the echo substudy of the IDEAL trial.
AB  - BACKGROUND: Abnormalities of cardiac structure and function are common in
      patients undergoing dialysis, and cardiovascular disease is the major cause of
      mortality in this group. Heart failure is a common clinical manifestation of
      cardiovascular disease and is preceded by left ventricular hypertrophy (LVH).
      There are variable reports about the impact of dialysis on LVH, both deleterious
      and beneficial. Our study investigated whether the timing of the initiation of
      dialysis therapy had an impact on cardiac structure and function. STUDY DESIGN:
      Randomized controlled trial. SETTING & PARTICIPANTS: This is a cardiac substudy
      involving 182 patients with stage 5 chronic kidney disease in the IDEAL
      (Initiating Dialysis Early and Late) trial. INTERVENTION: The IDEAL trial
      randomly assigned patients on the basis of estimated glomerular filtration rate
      (eGFR), calculated using the Cockcroft-Gault equation, to start dialysis therapy
      early (GFR, 10-14 mL/min/1.73 m(2)), with the others starting late (GFR, 5-7
      mL/min/1.73 m(2)). OUTCOMES & MEASUREMENTS: Echocardiograms were obtained at
      baseline and 12 months after randomization. Primary outcomes were change in left
      ventricular mass indexed for height (LVMi) between baseline and 12 months, left
      ventricular ejection fraction, left ventricular systolic annular velocity, ratio
      of mitral inflow velocity (E) to mitral annular velocity (Ea) (E/Ea), and left
      atrial volume indexed for height (LAVi). RESULTS: LVMi at baseline was elevated,
      but similar in both groups, with no significant change within or between groups
      at 12 months. E/Ea and LAVi were increased at baseline, consistent with
      significant diastolic dysfunction; there were no differences between groups at 12
      months and no changes were observed for left ventricular volumes, left
      ventricular ejection fraction, stroke volume, and other echocardiographic
      parameters. LIMITATIONS: Small multicenter study using echocardiography.
      CONCLUSIONS: Advanced cardiac disease in these patients with stage 5 chronic
      kidney disease did not progress during the 12-month study period and planned
      early initiation of dialysis therapy did not result in differences in any
      echocardiographic variables of cardiac structure and function.

PMID- 23157940
TI  - Introduction: roles that intracellular beta amyloid (Abeta) may have during
      disease.

PMID- 23157941
TI  - Is it time to rethink nutrition communications? A 5-year retrospective of
      Americans' attitudes toward food, nutrition, and health.

PMID- 23157942
TI  - Predictors of use of pain medications for persistent knee pain after primary
      Total Knee Arthroplasty: a cohort study using an institutional joint registry.
AB  - INTRODUCTION: To study the use of pain medications for persistent index knee pain
      and their predictors after primary Total Knee Arthroplasty (TKA). METHODS: The
      Mayo Total Joint Registry collects patient-reported data including pain
      medication use on all patients who undergo TKA. We used data from patients who
      underwent primary TKA from 1993-2005. We examined whether gender, age (reference,
      <= 60 yrs), body mass index (BMI; reference, <25 kg/m2), comorbidities measured
      by Deyo-Charlson index (5-point increase), anxiety and depression predicted use
      of pain medications (non-steroidal anti-inflammatory drugs (NSAIDs) and opioids)
      2- and 5-years after primary TKA. Multivariable logistic regression additionally
      adjusted for operative diagnosis, American Society of Anesthesiologists (ASA)
      score, implant fixation and distance from the medical center. RESULTS: 7,139 of
      the 10,957 eligible (65%) at 2-years and 4,234 of 7,404 eligible (57%) completed
      questionnaires. Significant predictors of NSAIDs use were (Odds ratio (95%
      confidence interval)): male gender at 2- and 5-years, 0.5 (0.4, 0.6) and 0.6
      (0.5, 0.8); age >70-80 years, 0.7 (0.5, 0.9), 0.6 (0.4, 0.8); and depression, 1.4
      (1.0, 1.8) and 1.7 (1.1, 2.5). BMI >= 40 was associated with NSAIDs use only at 2
      years, 1.6 (1.1, 2.5). Significant predictors of opioid pain medication use at 2-
      and 5-years were: male gender, 0.5 (0.3, 0.9) and 0.4 (0.2, 0.8); age >70-80
      years, 0.3 (0.1, 0.6), 0.3 (0.1, 0.8); and anxiety, 3.0 (1.6, 5.7) and 4.0 (1.7,
      9.4). CONCLUSIONS: Female gender and younger age were associated with higher risk
      of use of NSAIDs and opioids after primary TKA. Depression was associated with
      higher NSAID use and anxiety with higher opioid pain medication use after primary
      TKA.

PMID- 23157943
TI  - The quality of indigenous identification in administrative health data in
      Australia: insights from studies using data linkage.
AB  - BACKGROUND: Missing or incorrect Indigenous status in health records hinders
      monitoring of Indigenous health indicators. Linkage of administrative data has
      been used to improve the ascertainment of Indigenous status. Data linkage was
      pioneered in Western Australia (WA) and is now being used in other Australian
      states. This systematic review appraises peer-reviewed Australian studies that
      used data linkage to elucidate the impact of under-ascertainment of Indigenous
      status on health indicators. METHODS: A PubMed search identified eligible studies
      that used Australian linked data to interrogate Indigenous identification using
      more than one identifier and interrogated the impact of the different identifiers
      on estimation of Indigenous health indicators. RESULTS: Eight papers were
      included, five from WA and three from New South Wales (NSW). The WA papers
      included a self-identified Indigenous community cohort and showed improved
      identification in hospital separation data after 2000. In CVD hospitalised
      patients (2000-05), under-identification was greater in urban residents, older
      people and socially more advantaged Indigenous people, with varying algorithms
      giving different estimates of under-count. Age-standardised myocardial infarction
      incidence rates (2000-2004) increased by about 10%-15% with improved
      identification. Under-ascertainment of Indigenous identification overestimated
      secular improvements in life expectancy and mortality whereas correcting
      infectious disease notifications resulted in lower Indigenous/ non-Indigenous
      rate ratios. NSW has a history of poor Indigenous identification in
      administrative data systems, but the NSW papers confirmed the usefulness of data
      linkage for improving Indigenous identification and the potential for very
      different estimates of Indigenous disease indicators depending upon the algorithm
      used for identification. CONCLUSIONS: Under-identification of Indigenous status
      must be addressed in health analyses concerning Indigenous health differentials -
      they cannot be ignored or wished away. This problem can be substantially
      diminished through data linkage. Under-identification of Indigenous status
      impacts differently in different disease contexts, generally resulting in under
      estimation of absolute and relative Indigenous health indicators, but may
      perversely overestimate Indigenous rates and differentials in the setting of
      stigma-associated conditions such as sexually-transmitted and blood-borne virus
      infections. Under-numeration in Census surveys also needs consideration to
      address the added problem of denominator undercounts.

PMID- 23157944
TI  - Outcomes after listing with a requirement for a prospective crossmatch in
      pediatric heart transplantation.
AB  - BACKGROUND: Allosensitization is associated with inferior waitlist outcomes in
      pediatric heart transplant candidates, presumably because of the requirement for
      a negative prospective crossmatch. However, there are no reports of heart
      transplant candidate outcomes according to prospective crossmatch requirements.
      METHODS: We analyzed data on all children listed for isolated heart
      transplantation from 1995 to 2009 in the USA according to prospective crossmatch
      requirement (PXMR). Primary objectives were to describe the prevalence of PXMR at
      and during listing and to compare waitlist and post-transplant survival for
      patients based on PXMR. Patients with a PXMR during listing include those with a
      PXMR at the time of listing as well as those who were designated by the listing
      center as needing a prospective crossmatch at some point after being placed onto
      the waitlist. RESULTS: Among 6,343 listed children, 7.7% had a requirement for a
      prospective crossmatch at the time of listing and 11.8% had a requirement for a
      prospective crossmatch during listing. After controlling for risk factors
      associated with inferior survival, PXMR at listing was associated with increased
      waitlist mortality (HR 1.32, 95% CI 1.10 to 1.56; p = 0.003). Recipients with a
      PXMR during listing more commonly had a positive DSXM (22.1% vs 10.3%, p <
      0.0001), as did recipients who carried a PXMR throughout listing (21.7% vs 11.3%,
      p = 0.004). However, there was no significant difference in post-transplant
      survival on the basis of a PXMR during listing (HR 1.04, 95% CI 0.87 to 1.25; p =
      0.67). Nearly 30% of recipients with a PXMR during listing had a peak pre
      transplant PRA <= 10%. CONCLUSIONS: PXMR increases the likelihood of death while
      awaiting, but not after, pediatric heart transplantation. Further study is
      necessary to understand how PXMR is applied, and changes, after listing for
      pediatric heart transplantation.

PMID- 23157946
TI  - Pancreatic cancer circulating tumour cells express a cell motility gene signature
      that predicts survival after surgery.
AB  - BACKGROUND: Most cancer deaths are caused by metastases, resulting from
      circulating tumor cells (CTC) that detach from the primary cancer and survive in
      distant organs. The aim of the present study was to develop a CTC gene signature
      and to assess its prognostic relevance after surgery for pancreatic ductal
      adenocarcinoma (PDAC). METHODS: Negative depletion fluorescence activated cell
      sorting (FACS) was developed and validated with spiking experiments using cancer
      cell lines in whole human blood samples. This FACS-based method was used to
      enrich for CTC from the blood of 10 patients who underwent surgery for PDAC.
      Total RNA was isolated from 4 subgroup samples, i.e. CTC, haematological cells
      (G), original tumour (T), and non-tumoural pancreatic control tissue (P). After
      RNA quality control, samples of 6 patients were eligible for further analysis.
      Whole genome microarray analysis was performed after double linear amplification
      of RNA. 'Ingenuity Pathway Analysis' software and AmiGO were used for functional
      data analyses. A CTC gene signature was developed and validated with the nCounter
      system on expression data of 78 primary PDAC using Cox regression analysis for
      disease-free (DFS) and overall survival (OS). RESULTS: Using stringent
      statistical analysis, we retained 8,152 genes to compare expression profiles of
      CTC vs. other subgroups, and found 1,059 genes to be differentially expressed.
      The pathway with the highest expression ratio in CTC was p38 mitogen-activated
      protein kinase (p38 MAPK) signaling, known to be involved in cancer cell
      migration. In the p38 MAPK pathway, TGF-beta1, cPLA2, and MAX were significantly
      upregulated. In addition, 9 other genes associated with both p38 MAPK signaling
      and cell motility were overexpressed in CTC. High co-expression of TGF-beta1 and
      our cell motility panel (>= 4 out of 9 genes for DFS and >= 6 out of 9 genes for
      OS) in primary PDAC was identified as an independent predictor of DFS (p=0.041,
      HR (95% CI) = 1.885 (1.025 - 3.559)) and OS (p=0.047, HR (95% CI) = 1.366 (1.004 
      1.861)). CONCLUSIONS: Pancreatic CTC isolated from blood samples using FACS
      based negative depletion, express a cell motility gene signature. Expression of
      this newly defined cell motility gene signature in the primary tumour can predict
      survival of patients undergoing surgical resection for pancreatic cancer. TRIAL
      REGISTRATION: Clinical trials.gov NCT00495924.

PMID- 23157945
TI  - Radiotherapy for tumors of the stomach and gastroesophageal junction--a review of
      its role in multimodal therapy.
AB  - There is broad consensus on surgical resection being the backbone of curative
      therapy of gastric- and gastroesophageal junction carcinoma. Nevertheless,
      details on therapeutic approaches in addition to surgery, such as chemotherapy,
      radiotherapy or radiochemotherapy are discussed controversially; especially
      whether external beam radiotherapy should be applied in addition to chemotherapy
      and surgery is debated in both entities and differs widely between regions and
      centers. Early landmark trials such as the Intergroup-0116 and the MAGIC trial
      must be interpreted in the context of potentially insufficient lymph node
      resection. Despite shortcomings of both trials, benefits on overall survival by
      radiochemotherapy and adjuvant chemotherapy were confirmed in populations of D2
      resected gastric cancer patients by Asian trials.Recent results on junctional
      carcinoma patients strongly suggest a survival benefit of neoadjuvant
      radiochemotherapy in curatively resectable patients. An effect of chemotherapy in
      the perioperative setting as given in the MAGIC study has been confirmed by the
      ACCORD07 trial for junctional carcinomas; however both the studies by Stahl et
      al. and the excellent outcome in the CROSS trial as compared to all other
      therapeutic approaches indicate a superiority of neoadjuvant radiochemotherapy as
      compared to perioperative chemotherapy in junctional carcinoma patients. Surgery
      alone without neoadjuvant or perioperative therapy is considered suboptimal in
      patients with locally advanced disease.In gastric carcinoma patients,
      perioperative chemotherapy has not been compared to adjuvant radiochemotherapy in
      a randomized setting. Nevertheless, the results of the recently published ARTIST
      trial and the Chinese data by Zhu and coworkers, indicate a superiority of
      adjuvant radiochemotherapy as compared to adjuvant chemotherapy in terms of
      disease free survival in Asian patients with advanced gastric carcinoma. The
      ongoing CRITICS trial is supposed to provide reliable conclusions about which
      therapy should be preferred in Western patients with gastric carcinoma. If
      radiotherapy is performed, modern approaches such as intensity-modulated
      radiotherapy and image guidance should be applied, as these methods reduce dose
      to organs at risk and provide a more homogenous coverage of planning target
      volumes.

PMID- 23157948
TI  - [Careful selection and proper application of the inter-spinous dynamic
      stabilization for the lumbar spine].

PMID- 23157947
TI  - Differential expression of microRNAs in avian leukosis virus subgroup J-induced
      tumors.
AB  - Avian leukosis virus subgroup J (ALV-J) has become pandemic and induced serious
      clinical outbreaks in chickens in China. In particular, ALV-J induced various
      clinical tumors in infected chickens, which caused enormous economic losses to
      poultry. In this study, an infectious clone from an epidemic ALV-J Chinese
      isolate designated HLJ09SH01 was constructed and rescued. The rescued virus
      (named rHLJ09SH01) was inoculated into specific-pathogen-free (SPF) layer
      chickens, and infected chickens were observed for 238 days to explore the
      oncogenicity of rHLJ09SH01. As a result, 57.9% of rHLJ09SH01-infected chickens
      produced tumors. Accumulating evidence shows that microRNAs (miRNAs) have a close
      relationship with tumorigenesis. To gain more insight into the tumorigenesis of
      ALV-J, a miRNA microarray was performed as part of an investigation of changes in
      host miRNA expression in a liver tumor from ALV-J infected chickens. The results
      showed that four miRNAs were significantly differentially expressed; these data
      were verified using real-time PCR. Bioinformatics analysis showed the
      differentially expressed miRNAs to be involved in some tumorigenesis-related
      signaling pathways, such as the MAPK signaling pathway and the Wnt signaling
      pathway, which may represent a possible signaling pathway that was involved in
      the ALV-J-induced tumorigenesis.

PMID- 23157949
TI  - [Short-term clinical results of interspinous dynamic fixation of Coflex for the
      prevention of adjacent segment degeneration after lumbar fusion].
AB  - OBJECTIVE: To observe the short-term clinical results of the adjacent segment
      degeneration after the implantation of Coflex system at the interspinous space of
      adjacent segment to lumbar fusion. METHODS: Fifty patients with grade III disc
      (Thompson MRI classification) of adjacent segment to lumbar fusion were included
      and divided alternately into two groups according to the order of hospitalization
      from January to November 2009. Coflex system was implanted at the interspinous
      space of adjacent segment to lumbar fusion in 25 patients as Coflex group, the
      other 25 patients did not have any surgical treatment were as control group. The
      followed up time was 2 years. Visual analogue scale (VAS) score of low back pain,
      changes of disc height and motion range of adjacent segment to lumbar fusion on X
      ray imaging were evaluated by independent sample t-test or paired samples t-test.
      RESULTS: There were 22 patients in Coflex group and 21 patients in control group
      were followed up 2 years post-operation. The difference of VAS score between two
      groups was no significance (P > 0.05). In Coflex group, the change of
      postoperative disc height was no significance (P > 0.05), but the motion range
      was significantly reduced to 47% of the preoperative value (t = 7.99, P < 0.05).
      In control group, the postoperative disc height decreased slightly, without
      significant difference to the preoperative value (P > 0.05). Between the two
      groups, no differences of the disc height and motion range were found before
      operation, but the differences of the disc height changes (t = 6.7, P < 0.05) and
      motion rang (t = -14.5, P < 0.05) were significant in 2 years post-operation. No
      complications such as Coflex system loosen, immigration and spinal process
      fracture were occurred. CONCLUSIONS: Coflex system can obviously limit the motion
      range and maintain the disc space height of adjacent segment to lumbar fusion,
      and prevent its degeneration in some degree.

PMID- 23157950
TI  - [Clinical evaluation of interspinous process device Coflex for degenerative disk
      diseases].
AB  - OBJECTIVE: To study indications and complications of interspinous process device
      Coflex for degenerative disk diseases. METHODS: One hundred and eight patients
      with degenerative lumbar disc diseases were underwent procedures of surgical
      decompression and additional fixation of Coflex between November 2007 and October
      2010. Sixty-eight patients were male and the other fourty were female, and their
      average age was 53.5 years (range from 37 to 75 years). Fifty-nine patients were
      underwent surgery of excision of nucleus pulposus and Coflex fixation, 41
      patients were underwent surgery of decompression by fenestration and Coflex
      fixation, 6 patients were underwent surgery of topping-off, and 2 patients were
      underwent surgery of Coflex fixation for two level. Preoperative and
      postoperative visual analogue scales (VAS) and Oswestry disability index (ODI)
      were recorded, as well as height of ventral intervertebral space (HV), height of
      dorsal intervertebral space (HD), height of intervertebral foramen (HIF) and
      segmental range of motion (ROM). One-way ANOVA was used for statistical analysis.
      Surgical complications were also recorded. RESULTS: The average follow-up time
      was 28.8 months. All groups had apparent improvement of VAS and ODI, and
      maintained well to last follow-up (F = 6.16-25.92, P = 0.00). Statistical
      analysis showed that HD and HIF increased significantly in group with excision of
      nucleus pulposus and Coflex fixation and group with decompression by fenestration
      and Coflex fixation (F = 7.37 - 11.68, P < 0.05). Although both HD and HIF
      decreased one-year after surgery, they were still higher than those
      preoperatively (F = 6.31 and 7.05, P = 0.00). Preoperative segmental ROM was
      respectively 6.3 degrees  +/- 1.8 degrees  and 6.2 degrees  +/- 1.7 degrees  in
      group with excision of nucleus pulposus and Coflex fixation and group with
      decompression by fenestration and Coflex fixation, and 3.1 degrees  +/- 0.6
      degrees  and 3.0 degrees  +/- 0.8 degrees  at last follow-up. Three cases were
      found with device-related complications and five with non-device-related
      complications, and all five cased were cured after appropriate treatment.
      CONCLUSIONS: Surgical method assisted with Coflex has significant clinical
      efficacy for degenerative disc disease, it can maintain segmental stability,
      simultaneously, partly reserve movement. It's key to strictly master indications
      and precisely choose patients.

PMID- 23157951
TI  - [Device implanted complications of Coflex interspinous dynamic stabilization].
AB  - OBJECTIVE: To investigate device implanted complications and corresponding
      therapeutic strategies of Coflex interspinous dynamic stabilization system for
      lumbar spine intraoperatively and postoperatively. METHODS: From September 2008
      to August 2010, 133 cases of degenerative disease of lumbar spine including 62
      males and 71 females, ranging from 35 to 81 years of age (mean 60.8 years),
      underwent or planed to be underwent decompression with Coflex interspinous
      dynamic stabilization system were reviewed retrospectively, and 13 cases
      including 6 males and 7 females, ranging from 41 to 71 years of age (mean 58.6
      years), occurred device implanted complications. The Coflex implanted
      complications were analyzed, and therapeutic strategies according to different
      character were carried out, scores of visual analogue scale (VAS), Oswestry
      disability index(ODI) and effect-related data preoperatively, postoperatively,
      after conservative treatment and in final follow-up were evaluated with paired
      samples t test. RESULTS: Thirteen cases of Coflex implanted complications and
      treatment applied included: 3 cases occurred fracture of spinous processes
      intraoperatively were treated by pedicle screws instead; 2 cases occurred
      fracture of spinous processes postoperatively or during follow-up, including 1
      case underwent revision with pedicle screws, another 1 case treated with
      conservative treatment; 4 cases with degenerative coronal spondylolysis in
      surgical segments, 1 case with sagittal instability preoperatively, and 1 case
      with device dislodgment in follow-up all suffered aggravated pain and received
      conservative treatment; 1 case suffered implanted malposition intraoperatively
      was underwent internal fixation with pedicle screws instead; at length, 1 case
      with aggravated pain postoperatively and without definite reason received
      revision with internal fixation of pedicle screws demolishing the Coflex. The
      follow-up time of 13 cases ranged from 20 to 38 months (mean 27.6 months); and 7
      cases implanted Coflex with aggravated pain of lumbar and lower limb, but the
      position of device can still maintained, were received conservative treatment,
      and whose score of VAS and ODI in the final follow-up were 1.9 +/- 0.7 and 23.2
      +/- 3.4, and comparing to 6.1 +/- 1.1 and 58.1 +/- 3.0 preoperatively, evident
      improvement was got finally (t = 8.2 and 18.2, P < 0.01). Scores of VAS and ODI
      of 2 cases with Coflex implanted complications underwent revision with pedicle
      screws were also improved correspondingly. CONCLUSIONS: Coflex interspinous
      dynamic stabilization system implanted should be avoided to cases who suffered
      with osteoporosis, too narrow interspinous space and intervertebral coronal
      spondylolysis or sagittal instability; and choice of device, depth of
      implantation and intensity of clumping should be appropriate. For patients with
      symptom but device still in right position, conservative treatment can be carried
      out; but for patients subjected to malposition of device, failure of implantation
      intraoperatively or intolerance to device, revisions and salvages should be
      underwent with internal fixation of pedicle screws.

PMID- 23157952
TI  - [The efficacy and complication analysis of interspinous dynamic device (Wallis)
      in patients of degenerative lumbar disease].
AB  - OBJECTIVES: To review degenerative lumbar disease treated with Wallis and the re
      herniation cases after the implantation of Wallis, so as to evaluate the effect
      of the device. METHODS: From January 2009 to June 2010, a retrospective analysis
      was done and 48 patients (30 males and 18 females) with an average age of 43
      years (ranging from 17 to 69 years), who received stabilization of the segment
      using the Wallis device, were reviewed. The involved segments included: 4 cases
      at L(3-4), 38 cases at L(4-5), 6 cases at L(5)-S(1). Preoperative and
      postoperative visual analogue scales (VAS) and Oswestry disability index (ODI)
      were recorded to evaluate the clinical efficiency, imageology diversity was
      assessed by X-rays and MRI. RESULTS: All cases received fenestration and the
      implantation of Wallis. No surgery related complications were recorded. There
      were 48 cases were followed up. The average follow-up period was (20 +/- 4)
      months (12 - 30 months). The average ODI score dropped from 46 +/- 10 to 24 +/- 7
      (t = 12.765, P < 0.05). The average VAS for back and leg pain dropped from 8.1 +/
      1.6 to 2.1 +/- 1.1(t = 21.881, P < 0.05). Six patients with recurrent lower back
      and leg pain were diagnosed by MRI, as recurrent herniation (6/48, 12.5%). All re
      herniation occurred at L(4-5) level, between 2 and 13 months after the surgery.
      Three of the 6 patients underwent additional discectomy and fusion, others
      received conservative treatment. CONCLUSIONS: Although existing problems such as
      recurrence after surgery, the clinical outcome of Wallis in treating protrusion
      of lumbar intervertebral disc and lumbar stenosis is satisfied in middle-early
      stage.

PMID- 23157953
TI  - [Intermediate and long-term follow-up evaluation of posterior dynamic lumbar
      stabilization in lumbar degenerative disease].
AB  - OBJECTIVE: To evaluate the intermediate and long-term follow-up effect of
      posterior dynamic lumbar stabilization in lumbar degenerative disease. METHODS:
      The clinical outcomes of 96 patients (male 51, female 45, age from 21 to 68
      years, mean 41.5 years) whose follow-up time were more than 2 years with lumbar
      degenerative disease treated by posterior decompression with Wallis posterior
      dynamic lumbar stabilization implant or combined with posterior lumbar fusion
      from August 2007 to January 2010 were retrospectively studied, and assessed with
      visual analogue scale (VAS) and spinal operative standard of Chinese Medical
      Association. The early and long-term follow-up effect and complications
      associated with Wallis posterior dynamic lumbar stabilization were recorded. The
      height of intervertebral space at the treated level in lateral plain film were
      measured at preoperatively, 3 month postoperatively and last follow-up,
      respectively. The finds of MRI obtained at over 6 month postoperative were
      recorded. RESULTS: The operative procedure of Wallis posterior dynamic lumbar
      stabilization implant was easy and less invasive. The VAS scores were 78 +/- 24,
      28 +/- 16 and 14 +/- 12 preoperatively, 3 month postoperatively and last follow
      up, respectively. The good or excellent result was 91.7% at the last follow-up.
      No complication related with Wallis posterior dynamic lumbar stabilization was
      found. The rate of patient's satisfaction with the Wallis implant operation was
      95.8%. The disc height at the treated level in lateral plain film were (8.2 +/-
      3.7), (10.4 +/- 2.6) and (10.1 +/- 1.9) mm at preoperatively, 3 month
      postoperatively and last follow-up, respectively. There is no further
      degenerative change found in MRI obtained at over 6 month postoperative. MRI 1
      year after Wallis procedure showed rehydration of the formerly black disc at the
      treated level. CONCLUSIONS: It is easy and safe to use Wallis posterior dynamic
      lumbar stabilization in treatment of degenerative lumbar disease, and the effect
      of the intermediate and long-term follow-up more than 2 years is good. The Wallis
      system provides an alternative for treatment of lumbar degenerative disease.

PMID- 23157954
TI  - [Laparoscopic distal pancreatectomy: the experience of 68 cases in a single
      centre].
AB  - OBJECTIVE: To evaluate the feasibility and efficacy of laparoscopic distal
      pancreatectomy. METHODS: Totally 68 patients (male 23, female 45) aged 17 to 77
      years, with distal pancreatic lesions, underwent laparoscopic distal
      pancreatectomy from November 2003 to December 2010. The clinical data were
      collected. Safety, feasibility and crucial technique manipulation were analyzed
      retrospectively. RESULTS: All 68 operations were successful with two cases
      conversion to open, including 48 cases combined with splenectomy, and 18 cases
      with preservation of spleen. Fourteen cases received with combination resection
      of multi-organs, including 4 cases with cholecystectomy, 1 case resection of
      right adrenal adenoma and cholecystectomy, 1 case with myomectomy and left
      ovarian teratomectomy; 1 case with right ovarian teratomectomy, 1 case with
      resection of left adrenal adenoma, 1 case with resection of both adrenal adenoma,
      1 case with resection of liver metastasis, 1 case with cholecystectomy and
      resection of liver metastasis, 1 case with resection of left adrenal adenoma and
      liver metastasis, 1 case with resection of left adrenal adenoma and colon and
      spleen, 1 case with biopsy of liver nodule. The mean operative time was (209 +/-
      58) minutes, the mean intraoperative blood loss was (191 +/- 123) ml, and the
      mean postoperative hospital stay was (8 +/- 4) days. The rate of overall
      postoperative complications was 18.1%, including an 12.1% rate of clinical
      pancreatic fistula. Only one case needed a reoperation, and there was no
      postoperative mortality. CONCLUSION: Laparoscopic distal pancreatectomy with or
      without splenectomy is safe and feasible in the treatment of most distal
      pancreatic tumors.

PMID- 23157955
TI  - [Prognostic effect of postoperative resection-margin status for intraoperative
      positive resection margins in patients with advanced gastric cancer].
AB  - OBJECTIVES: To investigate prognostic effect of postoperative resection-margin
      status for intraoperatively positive resection margin in advanced gastric cancer
      and discuss the treatment choice for intraoperatively positive resection margins.
      METHODS: A retrospective study was investigated in 64 advanced gastric cancer
      patients with positive resection margin after potentially curative resection. The
      survival between 50 patients who was re-excised to a negative resection margin
      (NR group) and 14 patients who were left with positive resection margin (PR
      group) was compared. Prognostic factors were analyzed using univariate and
      multivariate Cox regression model analysis. RESULTS: The median survival in the
      PR group was 17.0 months (95%CI: 11.6 - 22.4) as compared with 23.0 months
      (95%CI: 20.5 - 25.5) in the NR group (P = 0.045). However, resection-margin
      status lost significance on multivariate analysis. In the subgroup of D2
      lymphadenectomy, the median survival in the PR group and NR group were 17.0
      months (95%CI: 12.0 - 22.0) and 24.0 months (95%CI: 19.8 - 28.1) respectively;
      multivariate analysis further identified resection margin status as an
      independent prognostic factor. CONCLUSIONS: Re-excision for intraoperatively
      positive margin to negative margin improves the prognosis of the patients with
      advanced gastric cancer, and re-excision is the first choice when intraoperative
      frozen section detects a positive margin. Routine frozen section of resection
      margin should be mandatory in all advanced gastric cancer undergoing potentially
      curative surgery.

PMID- 23157956
TI  - [Curative effect analysis of radical surgery for colon cancer invading duodenum].
AB  - OBJECTIVE: To discuss the clinicopathological characteristics and access the
      immediate- and long-term outcome of radical surgery in patients with colon cancer
      invading duodenum. METHODS: A retrospective review of 19 patients with colon
      cancer invading duodenum underwent radical surgery between 1995 and 2010 was
      performed. There were 7 male and 12 female, age ranged from 36 to 73 years with
      an average of 56 years. The main manifestations were abdominal pain, loss of
      weight, change of stool frequency and so on. The tumors located at the hepatic
      flexure in 15 patients. All of the patients underwent radical surgery, and none
      of the patients had positive resection margins. One patient underwent
      pancreaticoduodenectomy combined with right hemicolectomy (RH). Two patients
      underwent pylorus preserving pancreaticoduodenectomy combined with RH. One
      patient underwent duodenectomy combined with RH. Four patients underwent RH. And
      the other 11 patients underwent lateral duodenectomy combined with RH. RESULTS:
      There was no postoperative morbidity and mortality, and the 30-day mortality rate
      was 0. The median overall survival was 5.3 years. Overall 1 and 5 years survival
      rate were 94.4% and 70.4%, respectively. And 3 patients developed recurrence in 3
      years. CONCLUSIONS: The patients with colon cancer invading duodenum are lack of
      specific clinical manifestations. And the radical surgical procedure is safe,
      which could prolong the survival and improves the prognosis in these patients.

PMID- 23157957
TI  - [The therapeutic effect analysis of three kinds of methods for the management of
      post traumatic knee stiffness].
AB  - OBJECTIVES: To investigate the therapeutic effect of rehabilitation, arthroscopy
      and "hybrid technique" for posttraumatic knee stiffness (PTKS), and to make the
      best choice for the treatment. METHODS: From February 2004 to November 2009, 66
      patients suffered from PTKS were treated, and the clinical data were studied
      retrospectively, 36 male and 30 female patients with an average age of 41 years
      were analyzed, knee stiffness time averaged 15 months (0.5 - 108.0 months), 21
      cases of patients were treated with rehabilitation (rehabilitation group), 22
      cases of patients with arthroscopy + rehabilitation (arthroscopy group) and 23
      cases of patients with mini-invasive "hybrid technique" + rehabilitation (hybrid
      technique group). For each case, the difference of range of motion (ROM) and
      hospital for special surgery (HSS) score of the knee before and after the
      treatment were analyzed statistically. The characters of PTKS including the
      course of the disease, the degree of extensor mechanism involving, physical
      examination and other ancillary data were also analyzed. The management methods
      for PTKS were summarized. RESULTS: Total 66 cases were followed up ranging from
      24.0-72.5 months and the mean time was 34.2 months. The average ROM was improved
      obviously: rehabilitation group increased from 45 degrees  +/- 22 degrees  to 95
      degrees  +/- 24 degrees  (t = -11.2, P < 0.05), arthroscopy group from 47 degrees
      +/- 26 degrees  to 118 degrees  +/- 11 degrees  (t = -11.0, P < 0.05) and hybrid
      technique group from 36 degrees  +/- 22 degrees  to 110 degrees  +/- 14 degrees 
      (t = -13.4, P < 0.05). Both ROM and HSS score of the knee before and after the
      treatment for each group showed significant difference statistically (t = -9.1, 
      6.0, -5.2, P < 0.05). Wound necrosis, tearing, re-fracture and extension lag were
      not found. According to Judet standard at final follow-up, 15 cases were
      excellent, 3 cases good and 3 cases normal in rehabilitation group; 15 cases were
      excellent, 5 cases good and 2 cases normal in arthroscopy group; 14 cases were
      excellent, 8 cases good and 1 case bad. CONCLUSIONS: Pathology of PTKS is
      complex, satisfactory result could be obtained through individualized treatment
      program, which were established depend on the course of the disease, the degree
      of extensor mechanism involving, physical examination and ancillary data. The
      timely and effective surgical interference followed by a comprehensive
      rehabilitation program is the key point for satisfied outcome.

PMID- 23157958
TI  - [The use of anterior cervical discectomy and fusion with self-locking cages to
      treat multi-segmental cervical myelopathy].
AB  - OBJECTIVE: To investigate the use of anterior cervical discectomy and fusion with
      self-locking cages to treat multi-segmental cervical myelopathy. METHODS: From
      April 2008 to March 2010, anterior cervical discectomy and fusion with self
      locking cages were performed on 45 patients who suffered from multi-segmental
      cervical myelopathy, among of them there were 23 male and 22 female, aged from 32
      to 67 years (average 53 years). Recording the Japanese Orthopedic Association
      (JOA) scores and SF-36 scores in the protocol time point, in order to investigate
      the clinical outcome, meanwhile, accumulating the pre-operation and postoperation
      X-ray films of cervical spine for measuring the height of intervertebral space,
      whole curvature of cervical spine and the rate of fusion by repeated measures
      analysis of variance. RESULTS: The mean follow-up time was 28.4 months (24 - 35
      months). JOA scores ascended from preoperative 6.5 +/- 3.1 to postoperative 13.4
      +/- 1.7 (F = 17.84, P = 0.001), the 7 scores of SF-36 improved significantly
      after operation (t = 1.151 - 12.207, P < 0.05), but mental health not. The
      fineness rate was 91.1%. Height of disc space ascended from preoperative (5.5 +/-
      1.8) mm to postoperative (8.3 +/- 0.8) mm (F = 11.71, P = 0.043), globle
      curvature of cervical spine ascended from preoperative 5 degrees  +/- 7 degrees 
      to postoperative 10 degrees  +/- 14 degrees  (F = 234.53, P = 0.000), the change
      of the two index was significantly, respectively. Fat necrosis in one case and
      hematoma in another case at the bone donor-site were found, both of the two cases
      were cured by physiotherapy. All of the 45 cases (111 segments) achieved bone
      fusion. CONCLUSION: The use of anterior cervical discectomy and fusion with self
      locking cages to treat multi-segmental cervical myelopathy possess many
      advantages as follows: satisfactory clinical outcome, minimally invasive, higher
      fusion rate, higher orthopaedic ability.

PMID- 23157959
TI  - [Complete video-assisted thoracoscopic anatomic segmentectomy for pulmonary
      diseases: the early experiences].
AB  - OBJECTIVE: To evaluate the safety and feasibility of video-assisted thoracic
      surgery (VATS) anatomic segmentectomy for pulmonary diseases. METHODS: Between
      November 2009 and July 2011, 20 patients received consecutive VATS anatomic
      segmentectomy by single surgical group. There were 3 male and 17 female, aging
      from 32 to 81 years with a mean of 53 years. The patients included 12 cases of
      non-small cell lung cancer (NSCLC) (5 cases of bronchioloalveolar carcinoma, 6
      cases of adenocarcinoma, and 1 case of squamous cell carcinoma), 7 cases of
      benign diseases (3 cases of bronchiectasis, 2 cases of inflammatory pseudotumor,
      1 case of tuberculosis, and 1 case of sclerosing hemangioma) and 1 case of
      metastasis tumor. The locations of resected segments included 1 anterior segment,
      3 posterior segments, 4 apical segments, and 2 superior segments in the right
      side; and 5 lingular segments, 3 trisegments, and 2 superior segments in the left
      side. Simultaneously, 3 patients with bronchiectasis underwent segmentectomy and
      lobectomy, 1 of 6 patients with adenocarcinoma underwent lingulectomy and
      thymectomy. The pathological TNM stages of 12 NSCLC patients were 9 cases of
      T1aN0M0, 1 case of T1bN0M0 and 2 cases of T2aN0M0. RESULTS: Of these 20 patients,
      the median operative time was 155 minutes (range, 120 to 235 minutes), the median
      blood loss was 50 ml (range, 10 to 600 ml), the median drainage duration was 3 d
      (range, 1 to 6 d), and the median hospital stay was 6 d (range, 3 to 9 d). One
      patient who had undergone lingulectomy had a 600 ml intraoperative bleeding from
      lingular artery, and the bleeding was controlled by suturing the rupture under
      VATS. Bloody sputum occurred in 2 patients, prolonged air leak occurred in one
      patient for 5 days, and one patient developed subcutaneous emphysema that
      spontaneously resolved. No mortality was observed for 30 days after the surgery.
      CONCLUSIONS: VATS anatomic segmentectomy is a feasible and safe technique with
      acceptable operative time, less blood loss, fewer complications, and shorter
      hospital stay.

PMID- 23157960
TI  - [Surgical repair of truncus arteriosus in children: early results and long-term
      outcomes].
AB  - OBJECTIVE: To recite early results and long-term outcomes after surgical repair
      of persistent truncus arteriosus (PTA). METHODS: The clinic data of 54 patients
      underwent surgical repair for PTA from January 1999 to December 2009 was analyzed
      retrospectively. There were 36 male and 18 female patients, with a mean age of (9
      +/- 10) months (range, 1 to 38 months; median, 5 months). Preoperative mechanical
      ventilation was required in 5 patients. The surgical procedures were closure of
      ventricular septal defect and re-establishment of continuity between right
      ventricle and pulmonary artery. The right ventricular outflow tract (RVOT) was
      reconstructed by direct anastomosis pulmonary artery to right ventriculotomy with
      anterior wall patch enlargement (28 cases), or by inserting conduits (26 cases).
      Valvuloplasty were performed in 4 patients with truncal valves moderate to severe
      insufficiency and aortoplasty in 3 patients with interrupted aortic arch (IAA).
      RESULTS: There were 3 patients (5.6%) died of pulmonary hypertensive crisis in
      hospital. The mean duration of ventilation was 6.8 days in 5 patients who were
      intubated before operation, while the others were 3.6 days. Forty-seven (92.2%)
      patients were followed-up for mean (6.8 +/- 2.5) years (from 2.5 to 11.0 years).
      There were 2 patients with mild to moderate aortic regurgitation. One patient
      with aortic arch obstruction underwent balloon dilatation 2 years
      postoperatively. Among those patients who underwent direct anastomoses, 8 (32.0%)
      patients had pulmonary branch stenosis at 7 months to 1.5 years postoperatively,
      12 (48.0%) patients were freedom from surgical reintervention 5.0 to 11.0 years
      postoperatively. Among those inserting conduits, 7 patients (31.8%) had conduit
      stenosis at 2.8 to 7.0 years after operation. Reoperations were performed for
      RVOT in 15 patients and there was no mortality. CONCLUSIONS: It is difficult to
      treat the PTA patients with IAA, intra-mural coronary artery or mechanical
      ventilation support before operation. The technique of direct anastomosis between
      pulmonary artery and right ventricle offers the potential growth for RVOT, but
      bilateral pulmonary branch stenosis may be occurred at earlier period of
      postoperation in some patients.

PMID- 23157961
TI  - [Factors associated with increased blood loss in patients undergoing radical
      cystectomy in a contemporary series].
AB  - OBJECTIVE: To evaluate factors predictive of blood loss in radical cystectomy in
      a contemporary series. METHODS: From December 1996 to December 2008, clinical
      data of 233 patients who underwent radical cystectomy were reviewed
      retrospectively. Various preoperative and operative factors were assessed for
      their association with blood loss using univariate, multivariate regression and
      correlation analysis. RESULTS: One hundred eighty-one patients underwent open
      radical cystectomy and 52 cases were treated by laparoscopic radical cystectomy.
      Overall mean operative time was (339 +/- 84) minutes, and mean blood loss was
      (818 +/- 756) ml. On univariate analysis, body mass index (F = 9.039), history of
      pelvic operation (t = -4.365), anesthetic techniques (t = 3.125), surgical type
      (t = 6.643), use of Ligasure (t = 6.923), and urethra resection (t = -1.984)
      correlated with blood loss. However, multiple linear regression showed that body
      mass index (R(2) = 0.256, P < 0.001), history of pelvic operation (R(2) = 0.222,
      P < 0.001), use of Ligasure (R(2) = 0.172, P < 0.001), and surgical type (R(2) =
      0.271, P = 0.027) were significant predictors of blood loss. The transfusion was
      required in 176 of 233 patients (75.5%) with a median requirement of (649 +/-
      569) ml. Likewise logistical regression analysis revealed that older age (OR =
      3.2, P = 0.010), female gender (OR = 33.7, P = 0.013), anemia (OR = 6.6, P =
      0.039), increased blood loss (OR = 14.3, P < 0.001), open radical cystectomy (OR
      = 6.4, P = 0.036) and nonuse of Ligasure (OR = 10.1, P < 0.001) were predictors
      of transfusion need. CONCLUSIONS: Increased body mass index, history of pelvic
      operation, open radical cystectomy, and non-use of Ligasure were independent
      predictors of increased blood loss during radical cystectomy. Such a prediction
      formula has an important role in identifying high risk patient for increased
      blood loss and transfusion need before radical cystectomy.

PMID- 23157962
TI  - [The effects of nucleoside analogues on hepatitis B virus in hepatic lymph nodes
      of hepatitis B virus-associated liver transplantation recipients].
AB  - OBJECTIVE: To investigate the effects of nucleoside analogues on hepatitis B
      virus (HBV) in hepatic lymph nodes of hepatitis B related liver transplantation
      recipients who were hepatitis B surface antigen (HBsAg) positive but negative for
      serum HBV DNA. METHODS: From June 2010 to March 2011, thirty-six cases of
      hepatitis B related liver transplantation recipients [32 males, 4 females,
      average age (54 +/- 7) years] were divided into drug treatment group and non-drug
      treatment group according to the utility of nucleoside analogues. Drug treatment
      group was divided into two subgroups: drug treatment > 3 months group and drug
      treatment <= 3 months group. The hepatic lymph nodes in the hepatoduodenal
      ligament were taken during the operation of liver transplant. Using nested or
      semi-nested PCR, HBV DNA and the replicative form HBV cccDNA in hepatic lymph
      nodes were detected. Data were analyzed by Fisher's exact test. RESULTS: The
      positive rate of HBV DNA: the difference was not statistically significant
      between drug treatment group (72.7%, 16/22) and non-drug treatment group (14/14)
      (P = 0.062), the difference was not statistically significant between drug
      treatment > 3 months group (10/14) and drug treatment <= 3 months group (6/8) in
      the subgroups of drug treatment group (P = 1.000). The positive rate of HBV
      cccDNA: drug treatment group (22.7%, 5/22) was significantly lower than the non
      drug treatment (12/14) (P = 0.000), drug treatment > 3 months group (1/14) was
      significantly lower than drug treatment <= 3 months group (4/8) in the subgroups
      of drug treatment group (P = 0.039). CONCLUSIONS: Hepatic lymph nodes maybe one
      of the extrahepatic HBV reservoirs. Treating with nucleoside analogues more than
      3 months can significantly decrease the replication of HBV in hepatic lymph nodes
      of HBV associated liver transplantation recipients.

PMID- 23157963
TI  - [The expression of nicotinamide phosphoribosyl transferase and vascular
      endothelial growth factor-A in gastric carcinoma and their clinical
      significance].
AB  - OBJECTIVES: To study the expression of nicotinamide phosphoribosyl transferase
      (Nampt) and vascular endothelial growth factor-A (VEGF-A) in gastric carcinoma
      and investigate their correlations to clinicopathologic features and prognostic
      significance. METHODS: The proteins of Nampt and VEGF-A in 68 specimens of
      gastric carcinoma and 59 specimens normal gastric tissue were detected by
      immunohistochemistry during January 2000 to December 2004, and the 68 patients
      were followed up. RESULTS: Nampt protein was detected in the cytoplasm of both
      tissues, and Nampt in gastric carcinoma (13 +/- 5) were significantly higher than
      that in normal gastric tissue (6 +/- 3) (t = 7.46, P < 0.01). The expression of
      Nampt was correlated to invasive depth (F = 4.693, P = 0.034), lymph node
      metastasis (F = 4.027, P = 0.049), clinical TNM stage (F = 9.979, P = 0.002), but
      not to gender, age, tumor location, tumor size, differentiation (P > 0.05). The
      expression of Nampt is correlated with survival of patients that underwent
      surgical resection for gastric cancer. The survival rate of patients in negative
      of Nampt was very higher than that of the positive patients, and its co
      expression with VEGF-A showed a trend towards poorer survival. The positive
      correlation was found between the expression of Nampt and VEGF-A in gastric
      carcinoma (r = 0.293, P = 0.015). CONCLUSIONS: The expression of Nampt is
      positively correlated to that of VEGF-A in gastric carcinoma. The correlation
      between the expression of Nampt and VEGF-A in gastric carcinoma plays an
      important role cooperatively in carcinogenesis, development and metastasis of
      gastric carcinoma.

PMID- 23157964
TI  - [Effects of Baicalin on an orthotopic transplantation mouse model of mismatch
      repair gene deficient colorectal cancer].
AB  - OBJECTIVE: To study the anticancer effects of Baicalin on an orthotopic
      transplantation mouse model of mismatch repair gene deficient colorectal cancer.
      METHODS: Sixty orthotopic transplantation mice model of human colon cancer cell
      line HCT-116 expressing eGFP were established, which were divided randomly into
      negative controlled group (5% NaHCO3) and 50, 100, 200 mg/kg Baicalin groups. The
      nude mice were treated with intragastric infusion twice a day. Nude mice growth
      state, average weigh, inhibition rate of transplanted tumor, tumor metastasis and
      survival state were observed. RESULTS: At 14, 21 and 28 days after treatment with
      different dose of Baicalin, tumor growth velocity was significantly slower in the
      treatment groups, and tumor volume was significantly smaller than the controlled
      group (there were (832 +/- 637), (2012 +/- 1566) and (2494 +/- 1557) mm(3)
      respectively in 14, 21 and 28 days) (F = 4.433, P < 0.05). At the end point of
      study, survival state of 100 mg/kg group (13/15) was superior to controlled group
      (8/15) and 200 mg/kg group (8/15) (chi(2) = 4.665 and 3.980, P < 0.05).However,
      there were no significant differences in tumor metastasis and tumor surface
      vessel density. CONCLUSIONS: Baicalin has statistically significant effects in
      inhibiting tumor growth in an orthotopic transplantation mouse model of mismatch
      repair gene deficient colorectal cancer, and 100 mg/kg may be an ideal treatment
      dose.

PMID- 23157965
TI  - [Unilateral versus bilateral pedicle screw fixation in lumbar spinal fusion: a
      meta-analysis of available evidence].
AB  - OBJECTIVE: To evaluate the effectiveness of unilateral versus bilateral pedicle
      screw fixation in lumbar spinal fusion. METHODS: Studies on comparison between
      unilateral and bilateral pedicle screw fixation in lumbar spinal fusion were
      identified from Medline, EMBASE, Cochrane CENTRAL (Third Quarter 2011),
      ScienceDirect, OVID, SpringerLink and The China Biological Medicine Database, and
      searched several related journals by hand. The included trials were screened out
      according to the criterion of inclusion and exclusion. The quality of included
      trials was evaluated. Data were extracted by two reviewers independently. RevMan
      5.1.1 was used for data analysis. RESULTS: Seven studies involving 480 patients
      were included, 246 in unilateral group, and 234 in bilateral group. The results
      of meta-analysis indicated that statistically significant difference were
      observed between the two fixation procedures in mean operation time (MD = -24.39,
      95%CI: -33.16 to 15.61, P < 0.01), the amount of bleeding (MD = -118.73, 95%CI: 
      143.43 to -94.03, P < 0.01). There were no difference in inpatient stay, fusion
      rate, complication rate and excellent and good rate. CONCLUSIONS: Both unilateral
      and bilateral pedicle screw fixation are effective in lumbar spinal fusion. To
      compare with bilateral fixation, unilateral fixation can shorten operation time,
      reduce amount of bleeding and medical expenses. And there is a similar effect of
      inpatient stay, fusion rate, complication rate and excellent and good rate.

PMID- 23157967
TI  - Inflammatory predictors of ongoing pain 2 years following knee replacement
      surgery.
AB  - INTRODUCTION: The prevalence of unrelieved pain following total knee arthroplasty
      (TKA) is substantial. OBJECTIVE: We asked if cytokine markers of inflammation in
      preoperative serum or knee synovial fluid (SF) would predict pain 2 years
      following TKA. METHODS: Demographic data and functional outcomes were recorded at
      baseline and 2 years with the WOMAC index. Serum and SF tissue samples were
      collected at the time of surgery. Linear regression modeling was used to
      determine the relationship between SF/serum inflammatory markers and a lesser
      improvement in self reported pain at two years follow-up. RESULTS: Of our 28
      patient cohort, significant correlations between serum and SF levels were found
      for IL-1beta (p<0.002), MIP-1beta (p<0.001), adiponectin (p<0.001) and leptin
      (p<0.001). Adjusted analysis showed that greater SF concentrations of TNF-alpha,
      MMP-13 and IL-6 were independent predictors of less pain improvement at two years
      follow-up (p<0.05). CONCLUSIONS: Those patients, having ongoing pain despite no
      clinical or radiological cause, may have an inflammatory profile characterizing a
      predisposition to ongoing pain after TKA. LEVEL OF EVIDENCE: Prognosis study,
      Level 2.

PMID- 23157966
TI  - Pseudoexfoliation syndrome, a systemic disorder with ocular manifestations.
AB  - Pseudoexfoliation syndrome (PXS) is a systemic condition with eye manifestations.
      In the eye, pseudoexfoliation material deposits on various structures of the
      anterior segment. The nature of this material is mostly fibrillar with fibers
      made up of microfibrils and coated with amorphous material. The composition of
      these fibrils is diverse and includes basement membrane components as well as
      enzymes involved in extracellular matrix maintenance. Pseudoexfoliation is the
      most common cause of secondary open-angle glaucoma (pseudoexfoliation glaucoma,
      PXG) worldwide. The goal of this review is to summarize our knowledge on the
      genetics of this systemic disorder and its resultant ocular manifestations. PXS
      familial aggregation suggests genetic inheritance. PXS has been strongly
      associated with single nucleotide polymorphisms (SNPs) of the lysyl oxidase-like
      1 (LOXL1) gene on chromosome 15q24.1. Two of these SNPs confer a higher than 99%
      population attributable risk for PXS and PXG in the Nordic population; however,
      they carry different risks in different populations. The high risk haplotypes
      also vary among different populations. LOXL1 is one of group of the enzymes
      involved in the cross-linking of collagen and elastin in the extracellular
      matrix. Its function in connective tissue maintenance has been confirmed in mice;
      however, its actual role in PXS remains unclear. Contactin-associated protein
      like 2 also has a strong genetic association with PXS in a German cohort and is
      an attractive candidate molecule. It encodes for a protein involved in potassium
      channel trafficking. Other candidate genes linked to PXS include lysosomal
      trafficking regulator, clusterin, adenosine receptors, matrix metalloproteinase-1
      (MMP1), and glutathione transferase. These genes may be modifying genes for
      development of PXS and PXG.

PMID- 23157968
TI  - Anatomy of the anterior cruciate ligament related to hamstring tendon grafts. A
      cadaveric study.
AB  - BACKGROUND: The aim of modern techniques for anatomic reconstruction of the ACL
      is to reproduce ACL footprints, in order to restore anatomy and therefore normal
      biomechanics. Is there an oversizing of the hamstring grafts related to ACL
      dimensions? METHODS: Twenty-two paired cadaver knees were dissected. ACL
      dimensions at mid-portion and ACL footprints were measured after removing the
      synovial membrane. Hamstrings were harvested and prepared in a quadruple strand
      graft in order to measure the mean circumference. RESULTS: The average ACL tibial
      and femoral insertion site areas of the ACL were 117.9mm(2) (range, 90 to 130mm)
      and 96.8mm(2) (range, 80 to 121mm), respectively. The average diameter and cross
      sectional area of the ACL tendon at mid-portion were 6.1mm (range, 5 to 7mm) and
      29.2mm(2) (range, 20 to 38.9), respectively. The average diameter and cross
      sectional area of the 4-stranded hamstring tendons were 6.7 (range, 5 to 8) and
      35.3mm(2) (range, 20 to 50), respectively. There was a correlation between the 4
      stranded hamstring grafts and ACL dimensions (footprints, ligament at mid
      substance, p<0.01). The cross sectional area of hamstring tendon was
      significantly larger than the ACL area at mid-portion (mean 20.9%, p<0.05).
      CONCLUSION: With current ACL reconstruction techniques, the graft is oversized at
      a mean of 21%, despite a good correlation between the ACL and the hamstring
      tendon, especially among small subjects and women. The question arises whether
      the anatomic reconstruction of the ACL should fill ACL footprints or mimic the
      ligament itself. CLINICAL RELEVANCE: Hamstrings grafts are significantly larger
      than native ACL.

PMID- 23157969
TI  - In vivo detachment of a tibial stemmed component and subsequent extraction.
AB  - Revision knee arthroplasty may be complicated by bone loss and limited bone
      contact can lead to high stresses at the bone implant interfaces and subsequent
      loosening. We report an unusual case of loosening of a revision knee implant and
      the novel technique used for its extraction prior to further revision.

PMID- 23157970
TI  - Strengthening the rigour of population-wide, community-based obesity prevention
      evaluations.
AB  - OBJECTIVE: The aim of the present study was to review the methodological
      literature regarding evaluation methods for complex public health interventions
      broadly and, based on such methods, to critically reflect on the evaluation of
      contemporary community-based obesity prevention programmes. DESIGN: A systematic
      review of the methods and community-based literature was performed by one
      reviewer. RESULTS: The review identified that there is considerable scope to
      improve the rigour of community-based obesity prevention programmes through:
      prospective trial registration; the use of more rigorous research designs,
      particularly where routine databases including an objective measure of adiposity
      are available; implementing strategies to quantify and reduce the risk of
      selective non-participation bias; the development and use of validated
      instruments to assess intervention impacts; reporting of intervention process and
      context information; and more comprehensive analyses of trial outcomes.
      CONCLUSIONS: To maximise the quality and utility of community-based obesity
      prevention evaluations, programme implementers and evaluators need to carefully
      examine the strengths and pitfalls of evaluation decisions and seek to maximise
      evaluation rigour in the context of political, resource and practical
      constraints.

PMID- 23157971
TI  - Lower-limb amputee rehabilitation in Australia: analysis of a national data set
      2004-10.
AB  - OBJECTIVE: Examine demographics, clinical characteristics and rehabilitation
      outcomes of lower-limb amputees, using the Australasian Rehabilitation Outcomes
      Centre (AROC) database. METHODS: Lower-limb amputee rehabilitation separations
      between 2004 and 2010 were identified using AROC impairment codes 5.3-5.7.(1)
      Analysis was conducted by year, impairment code, Australian National Sub-acute
      and Non-Acute Patient (AN-SNAP) classification (S2-224, Functional Independence
      Measure (FIM) motor(Mot) score 72-91; S2-225, FIM (Mot) score 14-71) and states
      of Australia. RESULTS: Mean length of stay (LOS) for all lower-limb amputee
      episodes was 36.1 days (95% confidence interval (CI): 35.4-36.9). Majority of
      episodes were unilateral below knee (63.6%), males (71.8%) with a mean age of
      67.9 years (95% CI: 67.6-68.3). Year-on-year analysis revealed a trend for
      increasing LOS and decreasing age. Analysis by impairment code demonstrated no
      significant difference in rehabilitation outcomes. Analysis by AN-SNAP found that
      LOS was 16.2 days longer for S2-225 than for S2-224 (95% CI: 14.7-17.8, P<0.001),
      and FIM (Mot) change was 12.0 points higher for S2-225 than for S2-224 (95% CI:
      11.5-12.6, P<0.001). Analysis by states revealed significant variation in LOS,
      FIM (Mot) change and FIM (Mot) efficiency which may be associated with variations
      in organisation of rehabilitation services across states. CONCLUSION: Although
      amputees represented a comparatively small proportion of all rehabilitation
      episodes in Australia, their LOS was significant. Unlike many other
      rehabilitation conditions, there was no evidence of decreasing LOS over time. AN
      SNAP classes were effective in distinguishing rehabilitation outcomes, and could
      potentially be used more effectively in planning rehabilitation programs.

PMID- 23157972
TI  - Early use of MRI improves diagnostic accuracy in young adults with stroke.
AB  - OBJECTIVES: The misdiagnosis of acute ischemic stroke in young adults is a
      significant problem since patients may have many decades of potential disability.
      Also, proven therapies for acute stroke may not be administered if there is an
      initial misdiagnosis. We assessed the hypothesis that early use of MRI, arrival
      by ambulance, and presentation to a Primary Stroke Center (PSC) would be
      associated with a reduced rate of misdiagnosis. METHODS: A prospective database
      of young adults (ages 16-49 years) with ischemic stroke (final diagnosis provided
      by vascular neurologists) was reviewed. We collected information on several
      variables, including age, race, arrival by ambulance, whether brain MRI was
      performed within 48 h, and initial presentation to a PSC. Variables were tested
      against emergency department (ED) misdiagnosis using univariate and multivariate
      methods. RESULTS: 77 patients with a mean age of 37.9 years were reviewed. 48.3%
      of patients arrived by ambulance, 53.2% had a brain MRI within 48 h, and 23.4%
      initially presented to a PSC. The overall rate of ED misdiagnosis was 14.5%. In
      multivariate testing, performance of MRI within 48 h (p=0.023) was associated
      with a lower rate of misdiagnosis and age <35 years was linked with greater
      likelihood of misdiagnosis (p=0.047). CONCLUSIONS: Early performance of MRI leads
      to greater accuracy of stroke diagnosis in young adults presenting to the ED.
      Patients less than age 35 years have a greater risk of misdiagnosis. ED
      physicians and neurologists should consider early use of MRI in young adults with
      stroke-like deficits and diagnostic uncertainty.

PMID- 23157973
TI  - Ground reaction forces and plantar pressure distribution during occasional loaded
      gait.
AB  - This study compared the ground reaction forces (GRF) and plantar pressures
      between unloaded and occasional loaded gait. The GRF and plantar pressures of 60
      participants were recorded during unloaded gait and occasional loaded gait
      (wearing a backpack that raised their body mass index to 30); this load criterion
      was adopted because is considered potentially harmful in permanent loaded gait
      (obese people). The results indicate an overall increase (absolute values) of GRF
      and plantar pressures during occasional loaded gait (p < 0.05); also, higher
      normalized (by total weight) values in the medial midfoot and toes, and lower
      values in the lateral rearfoot region were observed. During loaded gait the
      magnitude of the vertical GRF (impact and thrust maximum) decreased and the shear
      forces increased more than did the proportion of the load (normalized values).
      These data suggest a different pattern of GRF and plantar pressure distribution
      during occasional loaded compared to unloaded gait.

PMID- 23157974
TI  - The effects of overall robot shape on the emotions invoked in users and the
      perceived personalities of robot.
AB  - The affective interaction between human and robots could be influenced by various
      aspects of robots, which are appearance, countenance, gesture, voice, etc. Among
      these, the overall shape of robot could play a key role in invoking desired
      emotions to the users and bestowing preferred personalities to robots. In this
      regard, the present study experimentally investigates the effects of overall
      robot shape on the emotions invoked in users and the perceived personalities of
      robot with an objective of deriving guidelines for the affective design of
      service robots. In so doing, 27 different shapes of robot were selected, modeled
      and fabricated, which were combinations of three different shapes of head, trunk
      and limb (legs and arms) - rectangular-parallelepiped, cylindrical and human-like
      shapes. For the experiment, visual images and real prototypes of these robot
      shapes were presented to participants, and emotions invoked and personalities
      perceived from the presented robots were measured. The results showed that the
      overall shape of robot arouses any of three emotions named 'concerned',
      'enjoyable' and 'favorable', among which 'concerned' emotion is negatively
      correlated with the 'big five personality factors' while 'enjoyable' and
      'favorable' emotions are positively correlated. It was found that the 'big five
      personality factors', and 'enjoyable' and 'favorable' emotions are more strongly
      perceived through the real prototypes than through the visual images. It was also
      found that the robot shape consisting of cylindrical head, human-like trunk and
      cylindrical head is the best for 'conscientious' personality and 'favorable'
      emotion, the robot shape consisting of cylindrical head, human-like trunk and
      human-like limb for 'extroverted' personality, the robot shape consisting of
      cylindrical head, cylindrical trunk and cylindrical limb for 'anti-neurotic'
      personality, and the robot shape consisting of rectangular-parallelepiped head,
      human-like trunk and human-like limb for 'enjoyable' emotion.

PMID- 23157975
TI  - Diagnostic and therapeutic yield of single balloon enteroscopy in patients with
      suspected small-bowel disease: results of the Italian multicentre study.
AB  - BACKGROUND: Limited data are available on the clinical impact of single balloon
      enteroscopy. AIMS: To evaluate the diagnostic and therapeutic yield of single
      balloon enteroscopy in patients with suspected small bowel disease. METHODS: Data
      on patients with suspected small bowel disease based on non-invasive imaging, who
      were subjected sequentially to enteroscopy were prospectively collected. RESULTS:
      131 procedures were performed in 111 patients. The mean procedure time was 61+/
      33min for the oral approach, and 78+/-41min for the anal approach. The mean
      insertion depth was 223+/-93cm beyond the ligament of Treitz, and 96+/-56 beyond
      the ileo-cecal valve. A diagnosis suspected with prior small bowel tests was
      confirmed in 82 patients, confidently excluded in 20, while in 9 the suspected
      area was not reached. Total enteroscopy was deemed clinically unnecessary in 94
      patients; when total enteroscopy was attempted, it was achieved in 8 out 17
      patients. Endoscopic therapeutic interventions were performed in 39 patients,
      medical treatment was started in 30, whereas 18 underwent to surgery. No major
      complications were registered. CONCLUSIONS: This study shows that single balloon
      enteroscopy appears to be an helpful and safe procedure with a high clinical
      impact, especially when it is placed in decision-making as a third level
      examination.

PMID- 23157976
TI  - Beneficial effect of splenic artery ligation on bacterial translocation after
      major liver resection in rats.
AB  - OBJECTIVE: In major liver resection, bacterial translocation appears to be an
      important mechanism in the pathogenesis of spontaneous infection. This study was
      designed to investigate the effects of splenic artery ligation on bacterial
      translocation after major liver resection. MATERIALS AND METHODS: Rats were
      divided into three groups: the sham operation group (SO group), the two-thirds
      partial hepatectomy group (PHx group) and the two-thirds partial hepatectomy plus
      splenic artery ligation group (PHx+Sp group). Bacterial translocation,
      endotoxemia, d-lactic acid and intestinal histology were analyzed among three
      groups. RESULTS: The rate of bacterial translocation was higher in the PHx rats
      than in the SO rats (65.0% vs. 6.67%; P=0.001), so that in the PHx+Sp rats
      (25.0%; P=0.011). Endotoxemia was not evident in the SO rats (0pg/ml) and blood
      endotoxin levels decreased in the PHx+Sp rats (1.47pg/ml) compared with the PHx
      rats (4.05pg/ml, P<0.001). d-lactic acid was also higher in both the PHx and
      PHx+Sp rats compared with the SO rats (39.09mg/ml, 23.36mg/ml, and 1.68mg/ml;
      P<0.01). CONCLUSION: Splenic artery ligation enhanced intestinal barrier function
      and diminished blood endotoxin levels and bacterial translocation in rats with
      major liver resection.

PMID- 23157977
TI  - Modeling the hepatic arterial buffer response in the liver.
AB  - In this paper we present an electrical analog model for the hepatic arterial
      buffer response (HABR), an intrinsic regulation mechanism in the liver whereby
      the arterial flow counteracts the changes in portal venous flow. The model itself
      is a substantial simplification of a previously published model, with nonlinear
      arterial and portal resistors introduced to account for the dynamic HABR effects.
      We calibrate the baseline model using published hemodynamic data, and then
      perform a virtual portal occlusion simulation where the portal vein is half or
      fully occluded. The simulation results, which suggest that the increased arterial
      flow cannot fully compensate lost portal perfusion, are consistent with clinical
      reports and animal model findings. Since HABR functions in both the whole liver
      and liver graft after transplantation, we also simulate blood flow in a virtual
      right-lobe graft by adjusting the electronic component parameters in the electric
      circuit, and our model is able to reproduce the portal venous hyperperfusion and
      hepatic arterial hypoperfusion conditions due to the HABR effects.

PMID- 23157978
TI  - A semiautomatic CT-based ensemble segmentation of lung tumors: comparison with
      oncologists' delineations and with the surgical specimen.
AB  - PURPOSE: To assess the clinical relevance of a semiautomatic CT-based ensemble
      segmentation method, by comparing it to pathology and to CT/PET manual
      delineations by five independent radiation oncologists in non-small cell lung
      cancer (NSCLC). MATERIALS AND METHODS: For 20 NSCLC patients (stages Ib-IIIb) the
      primary tumor was delineated manually on CT/PET scans by five independent
      radiation oncologists and segmented using a CT based semi-automatic tool. Tumor
      volume and overlap fractions between manual and semiautomatic-segmented volumes
      were compared. All measurements were correlated with the maximal diameter on
      macroscopic examination of the surgical specimen. Imaging data are available on
      www.cancerdata.org. RESULTS: High overlap fractions were observed between the
      semi-automatically segmented volumes and the intersection (92.5+/-9.0, mean+/-SD)
      and union (94.2+/-6.8) of the manual delineations. No statistically significant
      differences in tumor volume were observed between the semiautomatic segmentation
      (71.4+/-83.2 cm(3), mean+/-SD) and manual delineations (81.9+/-94.1 cm(3);
      p=0.57). The maximal tumor diameter of the semiautomatic-segmented tumor
      correlated strongly with the macroscopic diameter of the primary tumor (r=0.96).
      CONCLUSIONS: Semiautomatic segmentation of the primary tumor on CT demonstrated
      high agreement with CT/PET manual delineations and strongly correlated with the
      macroscopic diameter considered as the "gold standard". This method may be used
      routinely in clinical practice and could be employed as a starting point for
      treatment planning, target definition in multi-center clinical trials or for high
      throughput data mining research. This method is particularly suitable for
      peripherally located tumors.

PMID- 23157979
TI  - Lymph node ratio predicts the benefit of post-operative radiotherapy in oral
      cavity cancer.
AB  - BACKGROUND: The standard treatment for non-metastatic oral cavity squamous cell
      carcinoma (OCSCC) is surgical resection followed by post-operative radiotherapy
      (PORT) with/without chemotherapy in high risk patients. Given the substantial
      toxicity of PORT we assessed lymph node ratio (LNR) as a predictor of PORT
      benefit. DESIGN: By using the Surveillance, Epidemiology and End Results (SEER)
      database, we analyzed all node positive OCSCC patients diagnosed between 1988 and
      2007 who underwent neck dissection. LNR was categorized into three groups: < 6%,
      6-12.5% and > 12.5%. RESULTS: In 3091 subjects identified, median survival was
      32, 25 and 16 months for LNR Groups 1, 2 and 3, respectively. On multivariate
      analysis, survival was associated with age, race, grade, tumor size, nodal stage,
      extra-capsular extension, use of PORT and LNR. When stratified by LNR group, PORT
      was associated with a survival benefit only in Group 3 (LNR > 12.5%): 2 year
      survival 25% vs 37%. No benefit to PORT was seen when the LNR <= 12.5%: 2 year
      survival 51% vs 54%. CONCLUSION: A low LNR is associated with extended survival
      in LN positive OCSCC. The survival benefit associated with PORT in this disease
      appears to be limited to those with a LNR > 12.5%. Validation is required prior
      to the clinical implementation of our findings.

PMID- 23157980
TI  - Bioeffect modeling and equieffective dose concepts in radiation oncology-
      terminology, quantities and units.
AB  - The International Commission on Radiation Units and Measurements (ICRU) Report
      Committee on "Bioeffect Modeling and Biologically Equivalent Dose Concepts in
      Radiation Therapy" is currently developing a comprehensive and consistent
      framework for radiobiological effect modeling based on the equieffective dose,
      EQDX(alpha/beta), a concept encompassing BED and EQD2 as special cases.

PMID- 23157981
TI  - Correlation of in vitro lymphocyte radiosensitivity and gene expression with late
      normal tissue reactions following curative radiotherapy for breast cancer.
AB  - BACKGROUND AND PURPOSE: Identification of mechanisms of late normal tissue
      responses to curative radiotherapy that discriminate individuals with marked or
      mild responses would aid response prediction. This study aimed to identify
      differences in gene expression, apoptosis, residual DNA double strand breaks and
      chromosomal damage after in vitro irradiation of lymphocytes in a series of
      patients with marked (31 cases) or mild (28 controls) late adverse reaction to
      adjuvant breast radiotherapy. MATERIALS AND METHODS: Gene expression arrays,
      residual gammaH2AX, apoptosis, G2 chromosomal radiosensitivity and G0
      micronucleus assay were used to compare case and control lymphocyte radiation
      responses. RESULTS: Five hundred and thirty genes were up-regulated and 819 down
      regulated by ionising radiation. Irradiated samples were identified with an
      overall cross-validated error rate of 3.4%. Prediction analyses to classify cases
      and controls using unirradiated (0Gy), irradiated (4Gy) or radiation response (4
      0Gy) expression profiles correctly identified samples with, respectively, 25%,
      22% or 18.5% error rates. Significant inter-sample variation was observed for all
      cellular endpoints but cases and controls could not be distinguished.
      CONCLUSIONS: Variation in lymphocyte radiosensitivity does not necessarily
      correlate with normal tissue response to radiotherapy. Gene expression analysis
      can predict of radiation exposure and may in the future help prediction of normal
      tissue radiosensitivity.

PMID- 23157983
TI  - Electrical synapses getting translational.

PMID- 23157982
TI  - Using an integrated COC index and multilevel measurements to verify the care
      outcome of patients with multiple chronic conditions.
AB  - BACKGROUND: The increasing prevalence of multiple chronic conditions has
      accentuated the importance of coordinating and integrating health care services.
      Patients with better continuity of care (COC) have a lower utilization rate of
      emergency department (ED) services, lower hospitalization and better care
      outcomes. Previous COC studies have focused on the care outcome of patients with
      a single chronic condition or that of physician-patient relationships; few
      studies have investigated the care outcome of patients with multiple chronic
      conditions. Using multi-chronic patients as subjects, this study proposes an
      integrated continuity of care (ICOC) index to verify the association between COC
      and care outcomes for two scopes of chronic conditions, at physician and medical
      facility levels. METHODS: This study used a dataset of 280,840 subjects, obtained
      from the Longitudinal Health Insurance Database (LHID 2005), compiled by the
      National Health Research Institutes, of the National Health Insurance Bureau of
      Taiwan. Principal Component Analysis (PCA) was used to integrate the indices of
      density, dispersion and sequence into ICOC to measure COC outcomes - the
      utilization rate of ED services and hospitalization. A Generalized Estimating
      Equations model was used to verify the care outcomes. RESULTS: We discovered that
      the higher the COC at medical facility level, the lower the utilization rate of
      ED services and hospitalization for patients; by contrast, the higher the COC at
      physician level, the higher the utilization rate of ED services (odds ratio > 1;
      Exp(beta) = 2.116) and hospitalization (odds ratio > 1; Exp(beta) = 1.688). When
      only those patients with major chronic conditions with the highest number of
      medical visits were considered, it was found that the higher the COC at both
      medical facility and physician levels, the lower the utilization rate of ED
      services and hospitalization. CONCLUSIONS: The study shows that ICOC is more
      stable than single indices and it can be widely used to measure the care outcomes
      of different chronic conditions to accumulate empirical evidence. Concentrated
      care of multi-chronic patients by a single physician often results in
      unsatisfactory care outcomes. This highlights the need for referral mechanisms
      and integration of specialties inside or outside medical facilities, in order to
      optimize patient-centered care.

PMID- 23157984
TI  - Evaluation of Informed Choice for contraceptive methods among women attending a
      family planning program: conceptual development; a case study in Chile.
AB  - OBJECTIVE: To generate and validate a scale to measure the Informed Choice of
      contraceptive methods among women attending a family health care service in
      Chile. STUDY DESIGN AND SETTING: The study follows a multimethod design that
      combined expert opinions from 13 physicians, 3 focus groups of 21 women each, and
      a sample survey of 1,446 women. Data analysis consisted of a qualitative text
      analysis of group interviews, a factor analysis for construct validity, and kappa
      statistic and Cronbach alpha to assess scale reliability. RESULTS: The instrument
      comprises 25 items grouped into six categories: information and orientation,
      quality of treatment, communication, participation in decision making, expression
      of reproductive rights, and method access and availability. Internal consistency
      measured with Cronbach alpha ranged from 0.75 to 0.89 for all subscales (kappa,
      0.62; standard deviation, 0.06), and construct validity was demonstrated from the
      testing of several hypotheses. CONCLUSIONS: The use of mixed methods contributed
      to developing a scale of Informed Choice that was culturally appropriate for
      assessing the women who participated in the family planning program.

PMID- 23157985
TI  - CYP1A2 rs762551 polymorphism contributes to cancer susceptibility: a meta
      analysis from 19 case-control studies.
AB  - BACKGROUND: Genetic polymorphism (rs762551A>C) in gene encoding cytochrome P450
      1A2 (CYP1A2) has been shown to influence the inducibility of CYP1A2 expression
      and thus might be associated with risk of several types of human cancer. However,
      the results of previous studies on the associations of this polymorphism with
      risk of cancer are not all consistent. To clarify the potential contribution of
      CYP1A2 rs762551 to cancer risk, we performed a meta-analysis of the published
      case-control studies. METHODS: We used PubMed, Embase, OVID, ScienceDirect, and
      Chinese National Knowledge Infrastructure databases to identify the related
      publications for this meta-analysis. The pooled odds ratio (OR) and 95%
      confidence interval (CI) were calculated using random effect model to evaluate
      the association of rs762551 with cancer risk. A chi(2)-based Q-test was used to
      examine the heterogeneity assumption and the funnel plot and Egger's test were
      used to examine the potential publication bias. The leave-one-out sensitivity
      analysis was conducted to determine whether our assumptions or decisions have a
      major effect on the results of the review. RESULTS: Our analysis of 19 eligible
      case-control studies showed a significant association between rs762551C variant
      with risk of cancer in the genetic model of CC versus AA (OR = 1.30, 95% CI =
      1.02-1.64) and the dominant model (OR = 1.19, 95% CI = 1.04-1.36). In subgroup
      analysis based on ethnicity, the rs762551CC genotype was associated with
      increased cancer risk (OR = 1.29, 95% CI = 1.27-1.63 in co-dominate model and OR
      = 1.17, 95% CI = 1.02-1.34 in dominant model in Caucasians, but not in Asians and
      the mixed population. CONCLUSION: These results suggested that CYP1A2 rs762551
      polymorphism is likely to be associated with susceptibility to cancer in
      Caucasians.

PMID- 23157987
TI  - Screening instruments for depression in advanced cancer patients: what do we
      actually measure?
AB  - BACKGROUND: Patients in a palliative care trajectory frequently suffer from
      depression. To distinguish depression from normal sadness, the use of screening
      instruments could facilitate the diagnostic process. However, in palliative care,
      screening instruments may not discern physical symptom burden from psychological
      distress, due to the high number of physical symptoms in palliative patients.
      OBJECTIVES: The aim of this study was to explore physical symptom burden and
      psychological distress in patients with advanced cancer in relation to scores on
      screening instruments for depression. METHODS: Patients with advanced cancer were
      asked to fill out the Beck Depression Inventory (BDI-II), Beck Depression
      Inventory Primary Care (BDI-PC), Hospital Anxiety and Depression Scale (HADS),
      and Memorial Symptom Assessment Scale Short Form (MSAS-SF). The relationship
      between scores on screening tools for depression and different physical symptom
      clusters was explored. RESULTS: In the sample of 65 patients, screening
      instruments for depression correlated highly with different somatic symptom
      clusters. The BDI-II cognitive subscale was the only scale that was not
      significantly correlated with any of the somatic symptom clusters. CONCLUSION:
      Screening tools for the detection of depression in patients with advanced cancer
      may not provide an accurate evaluation of depression. These tools seem to measure
      physical symptom burden as well, especially when patients suffer from symptoms of
      the clusters fatigue/anorexia/cachexia, neuropsychology, debility, or pain. In
      this study, the BDI-II cognitive subscale seems to differentiate best from
      somatic symptom burden.

PMID- 23157986
TI  - Radioiodinated peptide probe for selective detection of oxidized low density
      lipoprotein in atherosclerotic plaques.
AB  - INTRODUCTION: Despite the significant effort in developing radioprobes for
      atherosclerosis, few have low molecular weight. Oxidized LDL (OxLDL), a highly
      proinflammatory and proatherogenic factor that is abundant in atherosclerotic
      plaques, plays a pivotal role in plaque destabilization, which makes OxLDL a
      relevant probe target. We developed a radioiodinated short peptide, AHP7, as a
      low molecular weight probe for specific OxLDL imaging and evaluated its utility
      using myocardial infarction-prone Watanabe heritable hyperlipidemic rabbits
      (WHHLMI). METHODS: [125I]AHP7 was designed and synthesized based on the sequence
      of Asp-hemolysin, an OxLDL binding protein extracted from Aspergillus fumigatus.
      In vitro binding studies with OxLDL having varying degrees of oxidation were
      performed. Radioactivity accumulation in the aorta was measured 30 min post
      administration in rabbits. Autoradiography and histological studies were
      performed using serial aorta sections. A radioiodinated scrambled peptide
      ([125I]AHP scramble) was used as a negative control. RESULTS: [125I]AHP7 bound to
      OxLDL in proportion to the degree of oxidation (R=0.91, P<0.0001) and was
      inhibited by unlabeled AHP7 in a concentration-dependent manner. The aorta
      accumulation level and aorta/blood and aorta/muscle ratios of [125I]AHP7 in
      WHHLMI were 2.8-, 1.3- and 1.8-fold higher, respectively, than those in control
      rabbits (P<0.001). Co-administration of AHP7 significantly reduced [125I]AHP7
      radioactivity in aorta sections (P<0.0001). Regional radioactivity levels in the
      aorta sections showed nonuniformity but similarity to the immunohistochemical
      OxLDL density. CONCLUSIONS: The potential of radioiodinated AHP7 for selectively
      imaging OxLDL was demonstrated both in vitro and in vivo.

PMID- 23157988
TI  - The impact of treatment non-compliance on mortality in people with type 1
      diabetes.
AB  - AIMS: To determine if a diagnostic record of poor treatment compliance
      (medication non-compliance and/or non-attendance at medical appointments) was
      associated with all-cause mortality in people with type 1 diabetes. METHODS: This
      is an observational cohort study of data extracted from The Health Improvement
      Network (THIN) database, comprising data on patients served by over 350 primary
      care practices in the U.K. Participants were included in the study if they had
      diagnostic codes indicative of type 1 diabetes. Treatment non-compliance was
      defined as missing one or more scheduled appointment, or one or more codes
      indicating medication non-compliance. RESULTS: Of 2946 patients with type 1
      diabetes, 867 (29.4%) had a record of either appointment non-attendance or
      medication non-compliance in the 30 month compliance assessment period. The
      crude, unadjusted mortality rate for those patients who were treatment non
      compliant was 1.462 (95% CI 0.954-2.205). Following adjustment for confounding
      factors, treatment non-compliance was associated with increased all-cause
      mortality (HR=1.642; 95% CI 1.055-2.554). CONCLUSIONS: Treatment non-compliance
      was associated with increased all-cause mortality in patients with type 1
      diabetes. Understanding and addressing factors that contribute to patient
      treatment non-compliance will be important in improving the life expectancy of
      patients with type 1 diabetes.

PMID- 23157990
TI  - Wernicke-Korsakoff-syndrome: under-recognized and under-treated.
AB  - BACKGROUND: Wernicke-Korsakoff syndrome (WKS) is a well described syndrome of
      neurological and cognitive problems that comprises both Wernicke's encephalopathy
      (WE) and Korsakoff syndrome (KS). WE is an acute neuropsychiatric disorder caused
      by thiamine deficiency. KS is a chronic consequence of thiamine deficiency with
      prominent impairment in memory formation. METHOD: The authors review the
      literature on the pathophysiology, presentation, and treatment of WKS, focusing
      on the acute identification and treatment of WE. RESULTS: Most cases of WE are
      missed by clinicians, likely because patients do not present with the classic
      signs associated with the condition. Attaining high serum levels of thiamine
      during treatment may be important to restore cognitive function as quickly as
      possible, though the exact dosing and route needed for effective treatment is
      unknown. Data indicates that the administration of intravenous (IV) thiamine has
      little risk. CONCLUSION: In order to prevent this potentially devastating
      disease, physicians should have a high index of suspicion for WKS and dose
      thiamine accordingly.

PMID- 23157991
TI  - A neuropsychiatric perspective of phenylketonuria I: overview of phenylketonuria
      and its neuropsychiatric sequelae.
AB  - Phenylketonuria (PKU) is an autosomal recessive metabolic genetic disorder that
      is associated with neuropsychiatric sequelae of varying severity. The natural
      history, epidemiology, and a history of the medical understanding and approaches
      to treatment of PKU are presented. Neurocognitive and neuropsychiatric sequelae
      of patients with untreated, early-treated, and continuously-treated PKU are
      described, and possible mechanisms for the symptoms are proposed. The authors
      propose an integrated approach to management of patients with PKU.

PMID- 23157992
TI  - The DSM 5 website proposals for somatic symptom disorder: three central problems.

PMID- 23157989
TI  - MALT lymphoma in labial salivary gland biopsy from Sjogren syndrome: importance
      of follow-up in early detection.
AB  - Mucosa-associated lymphoid tissue (MALT) lymphomas are known to occur in Sjogren
      syndrome (SS) patients, but reported cases in labial salivary glands (LSG) are
      rare. We report a case of 60-year-old female patient with SS who developed MALT
      lymphoma in the labial salivary glands during a 2-year time interval when she was
      participating in the Sjogren's International Clinical Collaborative Alliance, an
      ongoing longitudinal multisite observational study funded by the National
      Institutes of Health of the United States. At follow-up exam, LSG biopsy showed
      atypical diffuse infiltration by mononuclear cells of variable size and atypical
      nuclei affecting the whole specimen with destruction of glandular architecture,
      leading to a diagnosis of B-cell MALT lymphoma. Computerized tomography and bone
      marrow biopsy failed to show additional evidence of disease. Clinical, serologic,
      ocular, histologic and immunohistochemical findings are presented. A "watch and
      wait" policy was adopted with regular examinations.

PMID- 23157993
TI  - Metabolic syndrome: relative risk associated with post-traumatic stress disorder
      (PTSD) severity and antipsychotic medication use.
AB  - BACKGROUND: In recent years, numerous lines of converging evidence have revealed
      an association between post-traumatic stress disorder (PTSD) and impaired
      physical health outcomes, including cardiovascular disease and metabolic
      syndrome. Although these findings have been interpreted as indicating a direct
      association of PTSD with metabolic syndrome and obesity, previous studies have
      not addressed the important confound of antipsychotic drug usage in this
      population. Second generation antipsychotic medications themselves are associated
      with metabolic syndrome and obesity, and it is unclear whether the common
      utilization of these drugs in PTSD may account for some if not all of the
      observed metabolic problems. OBJECTIVE: The present study examined the relative
      contributions of PTSD severity and use of antipsychotic medications to risk of
      metabolic syndrome among veterans. METHOD: Cross-sectional clinical data,
      including five factors representing metabolic syndrome, psychiatric diagnoses,
      and medications were gathered from 253 veterans enrolling in mental health
      services. We used a logistic regression model to measure the relative association
      of antipsychotic medication use and PTSD severity on risk of metabolic syndrome.
      RESULTS: We found that antipsychotic medication usage was not uniquely associated
      with elevated risk of metabolic syndrome (Wald = 0.30, ns) when PTSD severity and
      other sociodemographic, psychiatric, and behavioral variables were accounted for.
      Furthermore, PTSD severity continued to be a significant and unique predictor of
      risk for metabolic syndrome (Wald = 4.04, p < 0.05). CONCLUSIONS: These findings
      suggest that chronic and moderately severe PTSD, independent of antipsychotic
      medications, is associated with increased risk of metabolic syndrome.

PMID- 23157994
TI  - Serotonin reuptake inhibitors and bleeding risks in major orthopedic procedures.
AB  - BACKGROUND: Risk of abnormal bleeding in surgery patients prescribed serotonin
      reuptake inhibitors (SRIs) is unclear. Considering the quantity of literature on
      abnormal gastrointestinal (GI) bleeding with SRIs, relatively little exists on
      SRI bleeding risks in surgical procedures. We investigated whether SRIs increase
      the risk of surgical bleeding in patients undergoing knee and hip total joint
      replacement. METHODS: RA retrospective case-control study was conducted among
      subjects undergoing primary total hip and knee replacement surgeries from January
      2005 to March 2011 at a single institution. The experimental group was defined by
      utilization of SRIs at the time of surgery (the independent variable). The
      control group was matched for age, sex, ethnicity, and type of surgery (hip or
      knee). Any case with preoperative hematocrit <30, platelets <100,000; abnormal
      prothrombin time, partial-prothrombin time, and international normalized ratio
      (INR), primary bleeding disorder, medical conditions, or medications associated
      with increased bleeding was excluded. All cases were randomly selected. RESULTS:
      RA total of 194 subjects (hip 104, knee 90) were included. Statistical analysis
      was performed on the SRI group (n = 71) and the control, non-SRI group (n = 123).
      No difference was found between the groups in estimated blood loss, hemoglobin,
      hematocrit, platelets, PT, PTT, and INR from preoperative to postoperative day 1,
      2, and 3. Furthermore, no subjects in either group required blood transfusions.
      CONCLUSION: SRIs were not associated with increased risk of bleeding in primary
      knee or hip replacement surgeries in this study. The hypothesis that SRIs
      increase the risk of bleeding based on presumptions about their action on
      platelet aggregation is uncertain and warrants further study.

PMID- 23157995
TI  - Rapid reversal of corticosteroid-induced mania with sodium valproate: a case
      series of 20 patients.
AB  - BACKGROUND: Glucocorticoids are widely used in medicine and are known to cause
      psychiatric side effects, including mania. There is anecdotal evidence that
      sodium valproate is effective for treating psychiatric side effects of
      glucocorticoids. OBJECTIVE: To describe a case series of 20 patients receiving
      corticosteroids for various medical conditions who developed manic-like symptoms.
      They were treated with sodium valproate while continuing on corticosteroids.
      METHOD: Patients treated with corticosteroids who reported to their physician
      subjective distress or who were openly disruptive in the ward were assessed by a
      consultation-liaison psychiatrist on the same day with the Young Mania Rating
      Scale. Immediately afterwards, blood was taken to measure the cortisol or
      dexamethasone level and then started on sodium valproate 500 mg twice daily.
      Valproate levels were measured on day 3 to adjust the dose. RESULTS: There was a
      significant, rapid improvement of symptoms within 48 hours after sodium valproate
      was initiated. Within 72 hours all patients were euthymic and remained so over
      the ensuing week. The only major side effect was hyperammonemia in 1 case which
      resolved when valproate was stopped. CONCLUSIONS: This case series shows that
      sodium valproate is a safe medication that rapidly reverses manic-like symptoms
      within a few days without needing to stop the corticosteroids, thus allowing the
      medical treatment to continue. The ability to continue treatment while
      controlling or ameliorating the psychiatric side effects of glucocorticoids with
      sodium valproate is an advance over previous approaches. The mechanism of this
      rapid action is unclear and deserves further study.

PMID- 23157997
TI  - Quetiapine-induced hepatocellular damage.

PMID- 23157996
TI  - Biopsychological stress factors in BRCA mutation carriers.
AB  - OBJECTIVE: Cancer risk-related stressors are prominent among BRCA mutation
      carriers. Loss of one's mother to a BRCA-associated cancer is an additional
      stressor, which may be related to an enhanced inflammatory response. This study
      examined the effect of mother's vital status on psychological factors and stress
      associated biomarkers among BRCA mutation carriers. The role of bereavement on
      biopsychological variables was also examined. METHODS: BRCA-carriers with known
      maternal transmission enrolled in the Gilda Radner Hereditary Cancer Program were
      invited to participate. Focus group composition was predetermined based on
      participants' personal cancer history and mother's vital status. Prior to the
      focus group, participants completed a Quality of Life (QOL) survey and collected
      a first morning saliva sample. Inflammatory biomarkers were analyzed from
      proximal archived serum. One day post focus group, a process survey, and morning
      saliva were collected. RESULTS: QOL was significantly lower for those whose
      mothers are deceased (n = 17) compared to those whose mothers are alive (n = 15)
      (P = 0.003) after adjusting for age, personal cancer history and prophylactic
      surgery. Similarly, those whose mothers are deceased reported significantly more
      perceived stress (P = 0.015), more intrusive thoughts related to cancer risk (P =
      0.049), and more anxiety (P = 0.003). Higher bereavement scores were
      significantly associated with QOL and psychological measures. Biomarker
      correlates were consistent with and significantly correlated to the patient
      reported psychological outcomes for those whose mothers were deceased.
      CONCLUSIONS: BRCA mutation carriers with a known maternal transmission whose
      mother is deceased report higher perceived stress and anxiety, lower QOL, and a
      stress-associated biomarker profile that is potentially globally immune
      suppressive.

PMID- 23157998
TI  - Self-injurious and aggressive behavior associated with a tacrolimus overdose.

PMID- 23157999
TI  - Atypical neuroleptic malignant syndrome associated with iloperidone
      administration.

PMID- 23158000
TI  - The Australian pharmacist workforce: employment status, practice profile and job
      satisfaction.
AB  - OBJECTIVE: The aims were to determine Australian registered pharmacists' current
      employment status, practice profile and professional satisfaction. METHOD: A
      questionnaire was mailed to all registered pharmacists (n=7764) on the Pharmacy
      Boards of Victoria and South Australia's registers; 19 were returned
      undeliverable. Quantitative data were entered and analysed using the Statistical
      Package for Social Sciences Version 17. Qualitative data were subjected to a
      thematic analysis. RESULTS: 1627 (21%) pharmacists responded: 259 (16%) were
      registered as pharmacists but no longer worked in the pharmacy profession. A
      total of 1366 respondents reported still working as pharmacists. Of the 1366, 912
      (67%) indicated that they spend most of their time in a clinical area; 233 (17%)
      spend most of their time in 'non-clinical pharmacist work (i.e. dispensing as
      technical supply)'; 216 (16%) worked in other non-clinical roles and; 1053 (77%)
      were professionally satisfied. CONCLUSION: Measuring the pharmacist workforce
      based on registration data significantly overestimates the available clinical
      pharmacist workforce: 708 (44%) respondents were no longer working in the
      profession, were not mainly involved in clinical practice or were working in non
      clinical roles. A significant re-professionalisation program is needed if
      pharmacists' unique knowledge and skills are to contribute to better healthcare
      delivery.

PMID- 23158002
TI  - [Pay attention to the hazard caused by nontuberculous mycobacterial infection].

PMID- 23158003
TI  - [The diagnosis of nontuberculous mycobacterial lung diseases].

PMID- 23158004
TI  - [Difficulty and confusion about treatment of nontuberculous mycobacterial lung
      diseases].

PMID- 23158001
TI  - ERbeta1 represses basal breast cancer epithelial to mesenchymal transition by
      destabilizing EGFR.
AB  - INTRODUCTION: Epithelial to mesenchymal transition (EMT) is associated with the
      basal-like breast cancer phenotypes. 60% of basal-like cancers have been shown to
      express wild-type estrogen receptor beta (ERbeta1). However, it is still unclear
      whether the ERbeta expression is related to EMT, invasion and metastasis in
      breast cancer. In the present study, we examined whether ERbeta1 through
      regulating EMT can influence invasion and metastasis in basal-like cancers.
      METHODS: Basal-like breast cancer cells (MDA-MB-231 and Hs578T) in which ERbeta1
      was either overexpressed or downregulated were analyzed for their ability to
      migrate and invade (wound-healing assay, matrigel-coated Transwell assay) as well
      as for the expression of EMT markers and components of the EGFR pathway
      (immunoblotting, RT-PCR). Coimmunoprecipitation and ubiquitylation assays were
      employed to examine whether ERbeta1 alters EGFR protein degradation and the
      interaction between EGFR and the ubiquitin ligase c-Cbl. The metastatic potential
      of the ERbeta1-expressing MDA-MB-231 cells was evaluated in vivo in a zebrafish
      xenotransplantation model and the correlation between ERbeta1 and E-cadherin
      expression was examined in 208 clinical breast cancer specimens by
      immunohistochemistry. RESULTS: Here we show that ERbeta1 inhibits EMT and
      invasion in basal-like breast cancer cells when they grow either in vitro or in
      vivo in zebrafish. The inhibition of EMT correlates with an ERbeta1-mediated
      upregulation of miR-200a/b/429 and the subsequent repression of ZEB1 and SIP1,
      which results in increased expression of E-cadherin. The positive correlation of
      ERbeta1 and E-cadherin expression was additionally observed in breast tumor
      samples. Downregulation of the basal marker EGFR through stabilization of the
      ubiquitin ligase c-Cbl complexes and subsequent ubiquitylation and degradation of
      the activated receptor is involved in the ERbeta1-mediated repression of EMT and
      induction of EGFR signaling abolished the ability of ERbeta1 to sustain the
      epithelial phenotype. CONCLUSIONS: Taken together, the results of our study
      strengthen the association of ERbeta1 with the regulation of EMT and propose the
      receptor as a potential crucial marker in predicting metastasis in breast cancer.

PMID- 23158005
TI  - [Diagnosis and treatment of diseases caused by rapidly growing mycobacteria].

PMID- 23158006
TI  - [Comparison of clinical manifestations between Mycobacterium avium-intracellulare
      complex and Mycobacterium abscessus pulmonary diseases].
AB  - OBJECTIVE: To compare the clinical manifestations of nontuberculous mycobacterial
      (NTM) pulmonary diseases caused by Mycobacterium avium-intracellulare complex
      (MAC) and Mycobacterium abscessus. METHODS: The clinical manifestations of 18
      patients with MAC and 9 patients with Mycobacterium abscessus pulmonary diseases
      diagnosed from 2010 to 2011 were reviewed. RESULTS: There were no significant
      differences in the gender, age, body mass index, predisposed diseases, symptoms
      and positive sputum acid-fast bacillus between MAC and Mycobacterium abscessus
      groups. Upper lobe cavities were more frequently observed in the MAC group
      (13/18), whereas nodular bronchiectatic changes were more frequent in the
      Mycobacterium abscessus group (3/9). Compared with MAC pulmonary diseases,
      several imaging characteristics were more common in the Mycobacterium abscessus
      group, including bilateral micro nodules (Mycobacterium abscessus group 8/9 vs
      MAC group 7/18), tree-in-bud sign (Mycobacterium abscessus group 7/9 vs MAC group
      6/18) and multiple bronchiectasis (Mycobacterium abscessus group 8/9 vs MAC group
      5/18). CONCLUSIONS: There was considerable overlap in clinical characteristics of
      MAC and Mycobacterium abscessus pulmonary diseases. However, bilateral micro
      nodules, tree-in-bud sign and multiple bronchiectasis were more frequently seen
      in Mycobacterium abscessus than in MAC pulmonary diseases, while upper lobe
      cavities were more frequently seen in MAC than in Mycobacterium abscessus
      pulmonary diseases.

PMID- 23158007
TI  - [The study of inter-simple sequences repeat genotyping based on one
      pentanucleotide repeat sequences in mycobacteria].
AB  - OBJECTIVE: To establish inter-simple sequences repeat (ISSR) molecular makers
      based on (CAGCG)n repeat sequence in mycobacteria. METHODS: The distribution of
      pentanucleotide repeat sequence (CAGCG)n in mycobacterial genomes was analyzed by
      MICdb 2.0 software in the microsatellite database. ISSR primer MISP6 based on
      (CAGCG)n sequences was designed and tested in mycobacterial strains, which
      included 17 mycobacterial strains and 41 Mycobacterium tuberculosis clinical
      strains. RESULTS: The abundances of pentanucleotide repeat sequences (CAGCG)n
      were high in most of the mycobacterial genomes and they were mainly located in
      the coding regions. The results of ISSR analysis in mycobacteria showed that 15
      reference strains from mycobacteria were clustered into 2 major clusters. The
      first cluster contained 2 subtypes and the second cluster contained 4 subtypes.
      Forty-one clinical strains from Mycobacterium tuberculosis were divided into 2
      major clusters by the analysis of MISP6 primer, and each cluster had 2 subtypes.
      CONCLUSION: ISSR primer MISP6 based on (CAGCG)n sequences can be used as a
      genetic marker to genotype mycobacterial strains.

PMID- 23158008
TI  - [A study on the relationship between single nucleotide polymorphisms of
      interleukin-22 and susceptibility to pulmonary tuberculosis].
AB  - OBJECTIVE: To study the association between single nucleotide polymorphisms
      (SNPs) of interleukin-22 (IL-22) gene and pulmonary tuberculosis. METHODS: From
      January 2009 to December 2010, clinical data of 479 patients with pulmonary
      tuberculosis in Shenzhen Third People's Hospital were collected. There were 212
      males, and 267 females, aging from 18 to 69 (mean 36 +/- 17) years, as well as
      358 healthy controls (162 males and 196 females), aging from 18 to 60 (mean 34 +/
      13) years. The genotype of SNPs (rs1182844, rs2227473, rs2227476, rs2227480,
      rs2227485, rs2227508) in IL-22 gene were determined with MassARRAY assay, after
      Hardy-Weinberg equilibrium test, and the allelic frequency and odds ratio were
      calculated. Peripheral blood mononuclear cells (PBMCs) from patients with
      different rs2227473 genotypes were stimulated with anti-CD3 and CD28, and then
      the IL-22 concentration in supernatant was determined with ELSIA. The SNP allelic
      frequencies between 2 groups were analyzed by chi-square and IL-22 concentration
      by t-test. RESULTS: The frequency of allele G of rs2227473 SNP was significantly
      higher in tuberculosis group than that in the control group (chi(2) = 7.448, P <
      0.01, OR = 1.509, 95%CI= 1.121 - 2.030). The other 5 SNPs allele frequency were
      not statistically significant between the 2 groups (chi(2) = 0.528 - 3.571, all P
      > 0.05). The secretion of IL-22 was significantly lower in PBMCs with genotype GG
      of rs2227473 SNP as compared to that in the others (GA/AA) (t = 2.686, P < 0.01).
      CONCLUSIONS: The results suggested that the rs2227473 SNP in IL-22 was associated
      with the risk of pulmonary tuberculosis. The allele G was the risk factor of
      pulmonary tuberculosis. The SNP (rs2227473) may play an important role in the
      protective immune process against tuberculosis by affecting the IL-22 expression
      of PBMCs.

PMID- 23158009
TI  - [The expressions of nerve growth factor and its tyrosine kinase A receptor on
      alveolar macrophages in a rat model of chronic obstructive pulmonary disease].
AB  - OBJECTIVE: To observe the expressions of nerve growth factor (NGF) and its
      tyrosine kinase A (TrkA) receptor on alveolar macrophage in a rat model of
      chronic obstructive pulmonary disease (COPD). METHODS: Forty healthy male SD rats
      were randomly divided into a control group and a COPD group. The COPD model was
      established by exposing the rats to cigarette smoke for 6 months, and lung
      function changes were measured. Lung histopathological changes were detected by
      HE staining. The expression of NGF protein in the supernatant of alveolar
      macrophage (AM) culture medium was detected by ELISA. Confocal microscopy was
      used to identify the separation and purification of AM from bronchoalveolar
      lavage fluid, and to detect semi-quantitatively the expression of TrkA receptor
      on AM. NGF and its TrkA receptor at the mRNA level were evaluated by real-time
      PCR. The differences among groups were calculated by one way ANOVA, and
      comparison between groups was made by t test. RESULTS: Significant decrease of
      pulmonary compliance [(0.15 +/- 0.03) ml/cm H(2)O (1 cm H2O = 0.098 kPa)] and
      minute ventilation [(0.045 +/- 0.004) L], and significant increase of airway
      resistance [(0.038 +/- 0.004) cm H2O*L(-1)*s(-1)] were found in the COPD group
      compared with the control group [(0.42 +/- 0.05) ml/cm H2O and (0.102 +/- 0.010)
      L and (0.016 +/- 0.002) cm H2O*L(-1)*s(-1), t = 9.46 - 12.99, respectively, all P
      < 0.01]. Alveolar wall thinning, alveolar septa breakdown, alveolar enlargement
      and emphysema were significant in the COPD rats. The expression of NGF protein in
      the supernatant of AM culture medium was enhanced in the COPD group [(3.79 +/-
      1.52) ng/L] compared with the controls [(0.94 +/- 0.27) ng/L, t = 4.13, P <
      0.05]. Mean fluorescence intensity of TrkA protein on AM in the COPD group (19.5
      +/- 1.5) was higher than that in the control group (11.2 +/- 1.9, t = 7.95, P <
      0.05). The expressions of NGF and TrkA at mRNA level in the COPD group (24.8 +/-
      6.0 and 9.0 +/- 3.3) were increased compared with the control group (1.0 +/- 0.2
      and 1.0 +/- 0.4, t = 8.48 and 5.16, all P < 0.05). CONCLUSIONS: The expressions
      of NGF and its TrkA receptor on AM in COPD group were increased, indicating that
      NGF and its TrkA receptor might be involved in the pathogenesis of COPD mediated
      by AM.

PMID- 23158010
TI  - [Relationship between serum substance P levels and excessive daytime sleepiness
      in patients with obstructive sleep apnea-hypopnea syndrome].
AB  - OBJECTIVE: To investigate the relationship between serum Substance P levels and
      excessive daytime sleepiness (EDS) in patients with obstructive sleep apnea
      hypopnea syndrome (OSAHS). METHODS: A total of 120 adult habitual snorers treated
      by respiratory physicians in First Hospital of Quanzhou Affiliated to Fujian
      Medical University were selected for this study. The patients were grouped as
      simple snorers and OSAHS by the results of polysomnography test. Thirty patients
      were in the simple snorer group, among whom 24 were male and 6 were female. Their
      average age was (48 +/- 15) years and average AHI was (2.8 +/- 1.6) events/hour.
      Ninety patients were in the OSAHS group, among whom 78 were male and 12 were
      female. Their average age was (49 +/- 12) years and average AHI was (37.1 +/-
      23.7) events/hour. EDS was assessed using the Epworth sleepiness scale (ESS).
      Substance P levels were analyzed with a radioimmunoassay. RESULTS: There was no
      significant difference in gender, age, and body mass index between the 2 groups.
      The ESS score for patients with OSAHS was (13 +/- 5), higher than that for
      patients in the simple snorer group (F = 10.299, P < 0.05). With increasing
      severity of OSAHS, the score increased. The serum Substance P level for OSAHS
      group was (132 +/- 27) ng/L, which was lower than that in the control (F = 3.048,
      P = 0.031), and decrease in Substance P level was most significant in patients
      with severe OSAHS. Pearson correlation analysis showed that Substance P levels in
      OSAHS patients were negatively correlated with ESS scores (r = -0.238, P < 0.05).
      CONCLUSIONS: Substance P levels were lower in OSAHS patients with higher degree
      of daytime sleepiness. Daytime sleepiness and Substance P level were interrelated
      in patients with OSAHS.

PMID- 23158011
TI  - [Research progress on LSR2 in mycobacteria].

PMID- 23158012
TI  - [Structure and function of mycobacterial proline-glutamic acid protein/proline
      proline-glutamic acid protein].

PMID- 23158013
TI  - Extraintestinal pathogenic Escherichia coli in poultry meat products on the
      Finnish retail market.
AB  - BACKGROUND: Extraintestinal pathogenic Escherichia coli bacteria (ExPEC) exist as
      commensals in the human intestines and can infect extraintestinal sites and cause
      septicemia. The transfer of ExPEC from poultry to humans and the role of poultry
      meat as a source of ExPEC in human disease have been discussed previously. The
      aim of the present study was to provide insight into the properties of ExPEC in
      poultry meat products on the Finnish retail market with special attention to
      their prevalence, virulence and phylogenetic profiles. Furthermore, the isolates
      were screened for possible ESBL producers and their resistance to nalidixic acid
      and ciprofloxacin was tested. METHODS: The presence of ExPEC in 219 marinated and
      non-marinated raw poultry meat products from retail shops has been analyzed. One
      E. coli strain per product was analyzed further for phylogenetic groups and
      possession of ten virulence genes associated with ExPEC bacteria (kpsMT K1, ibeA,
      astA, iss, irp2, papC, iucD, tsh, vat and cva/cv) using PCR methods. The E. coli
      strains were also screened phenotypically for the production of extended-spectrum
      beta-lactamase (ESBL) and the susceptibility of 48 potential ExPEC isolates for
      nalidixic acid and ciprofloxacin was tested. RESULTS: E. coli was isolated from
      207 (94.5%) of 219 poultry meat products. The most common phylogenetic groups
      were D (50.7%), A (37.7%), and B2 (7.7%). Based on virulence factor gene PCR,
      23.2% of the strains were classified as ExPEC. Two ExPEC strains (1%) belonged to
      [O1] B2 svg+ (specific for virulent subgroup) group, which has been implicated in
      multiple forms of ExPEC disease. None of the ExPEC strains was resistant to
      ciprofloxacin or cephalosporins. One isolate (2.1%) showed resistance to
      nalidixic acid. CONCLUSIONS: Potential ExPEC bacteria were found in 22% of
      marinated and non-marinated poultry meat products on the Finnish retail market
      and 0.9% were contaminated with E. coli [O1] B2 svg+ group. Marinades did not
      have an effect on the survival of ExPEC as strains from marinated and non
      marinated meat products were equally often classified as ExPEC. Poultry meat
      products on the Finnish retail market may have zoonotic potential.

PMID- 23158014
TI  - An emerging role for microRNAs in NF1 tumorigenesis.
AB  - MicroRNAs (miRNAs) are a class of non-coding RNA, which have recently been shown
      to have a wide variety of regulatory functions in relation to gene expression.
      Since their identification nearly 20 years ago, miRNAs have been found to play an
      important role in cancer, including in neurofibromatosis type 1 (NF1)-associated
      tumours. NF1 is the most commonly inherited tumour predisposition syndrome and
      can lead to malignancy via the development of malignant peripheral nerve sheath
      tumours (MPNSTs). Although the mechanisms by which benign neurofibromas develop
      into MPNSTs still remain to be elucidated, it is becoming increasingly clear that
      miRNAs play a key role in this process and have the potential to be used as both
      diagnostic and prognostic markers of tumorigenesis.

PMID- 23158015
TI  - Neonatal outcome of preterm infants born to mothers with abnormal genital tract
      colonisation and chorioamnionitis: a cohort study.
AB  - PURPOSE: We hypothesised that abnormal genital tract colonisation leading to an
      in utero inflammation/infection process, contributes to the risk of respiratory
      distress syndrome (RDS), patent ductus arteriosus (PDA), intra ventricular
      haemorrhage (IVH), bronchopulmonary dysplasia (BPD), retinopathy of prematurity
      (ROP) and necrotizing enterocolitis (NEC) in preterm infants. METHODS: 396
      placentas and umbilical cords of neonates born at 22-32weeks of gestation were
      evaluated. Genital tract and amniotic fluid swabs were cultured for aerobic and
      anaerobic bacteria. RESULTS: Chorioamnionitis significantly increases the risk
      for RDS (OR 1.74, 95% CI 1.14-2.65), NEC (OR 3.22, 95% CI 1.36-3.28) and ROP>2
      (OR 2.12, 95% CI 1.33-3.36). But the risk for IVH, PDA and BPD did not differ
      between the groups. Klebsiella pneumoniae (OR 5.33, 95% CI 1.06-26.79),
      Staphylococcus sp. (OR 18.39, 95% CI 2.32-145.2) and Enterococcus faecalis (OR
      10.7, 95% CI 1.27-89.9) showed a significant relationship with intrauterine
      inflammation processes. E. faecalis increased the risk for NEC (OR 6.13, 95% CI
      1.059-37.6). We did not note a link between ROP and genital tract colonisation.
      Interestingly PDA seems to be triggered by the presence of Pseudomonas aeruginosa
      (OR 2.38 95% CI 1.83-3.82). CONCLUSION: Our results show a link between K.
      pneumoniae, Staphylococcus sp., E. faecalis and intrauterine infection. E.
      faecalis increases the risk for NEC, and suggests a direct link between gram +
      bacteria, chorioamnionitis and NEC.

PMID- 23158016
TI  - Clinical outcome in IL-10- and IL-10 receptor-deficient patients with or without
      hematopoietic stem cell transplantation.
AB  - BACKGROUND: Inherited deficiencies of IL-10 or IL-10 receptor (IL-10R) lead to
      immune dysregulation with life-threatening early-onset enterocolitis. OBJECTIVES:
      We sought to gather clinical data of IL-10/IL-10R-deficient patients and devise
      guidelines for diagnosis and management, including hematopoietic stem cell
      transplantation (HSCT). METHODS: We enrolled 40 patients with early-onset
      enterocolitis and screened for mutations in IL10/IL10R using genetic studies,
      functional studies, or both of the IL-10 signaling pathway. Medical records of IL
      10/IL-10R-deficient patients were reviewed and compiled. RESULTS: Of 40 patients,
      we identified 7 with novel mutations, predominantly in consanguineous families
      with more than 1 affected member. IL-10/IL-10R-deficient patients had intractable
      enterocolitis, perianal disease, and fistula formation. HSCT was carried out in 2
      patients with IL-10 deficiency and 1 patient with IL-10R alpha chain deficiency
      and proved to be an effective therapy, leading to rapid improvement of clinical
      symptoms and quality of life. CONCLUSION: Because the defect in patients with IL
      10/IL-10R deficiency resides in hematopoietic lineage cells and their colitis is
      resistant to standard immunosuppressive therapy, HSCT should be considered early
      as a potentially curative therapeutic option.

PMID- 23158017
TI  - Changes in muscle activation patterns in response to enhanced sensory input
      during treadmill stepping in infants born with myelomeningocele.
AB  - Infants with myelomeningocele (MMC) increase step frequency in response to
      modifications to the treadmill surface. The aim was to investigate how these
      modifications impacted the electromyographic (EMG) patterns. We analyzed EMG from
      19 infants aged 2-10 months, with MMC at the lumbosacral level. We supported
      infants upright on the treadmill for 12 trials, each 30 seconds long.
      Modifications included visual flow, unloading, weights, Velcro and lcriction.
      Surface electrodes recorded EMG from tibialis anterior, lateral gastrocnemius,
      rectus femoris and biceps femoris. We determined muscle bursts for each stride
      cycle and from these calculated various parameters. Results indicated that each
      of the five sensory conditions generated different motor patterns. Visual flow
      and friction which we previously reported increased step frequency impacted
      lateral gastrocnemius most. Weights, which significantly decreased step frequency
      increased burst duration and co-activity of the proximal muscles. We also
      observed an age effect, with all conditions increasing muscle activity in younger
      infants whereas in older infants visual flow and unloading stimulated most
      activity. In conclusion, we have demonstrated that infants with myelomeningocele
      at levels which impact the myotomes of major locomotor muscles find ways to
      respond and adapt their motor output to changes in sensory input.

PMID- 23158018
TI  - Kicking velocity and physical, technical, tactical match performance for U18
      female football players--effect of a new ball.
AB  - We investigated kicking velocity and physical, technical, and tactical match
      performance for under-18 (U18) female football players and evaluated the effect
      of using a newly developed lighter smaller ball. Ten regional league teams
      participated. Maximal ball velocity was 4+/-1% higher when kicking the new ball
      (NB) compared with the standard ball (SB) in a laboratory testing situation
      (23.2+/-0.4 vs. 22.4+/-0.3 ms(-1); p<.05). Mean HR was similar during games with
      NB and SB (169+/-2 vs. 170+/-2 bmin(-1); p>.05), but lower-limb muscular RPE was
      lower with NB (4.2+/-0.4 vs. 5.2+/-0.3; p<.05). The number of activity changes
      (1387+/-76 vs. 1401+/-55), total distance covered (9.09+/-0.25 vs. 9.11+/-0.25
      km) and high-intensity running (1.04+/-0.08 vs. 1.11+/-0.07 km) were not
      different between NB and SB (p>.05). High-intensity running decreased (p<.05)
      from 0-20 to 60-80 min with NB (34%) and SB (37%). The number and success rate of
      long and short passes did not differ between NB and SB (p>.05). In conclusion,
      physiological demands were high in youth female football games, and decrements in
      running performance occurred towards the end of games. The players kicked faster
      and reported lower muscular exertion during games played with a lighter smaller
      ball, but locomotor activities, heart rate and overall technical-tactical game
      performance remained unaffected.

PMID- 23158019
TI  - Safety of falciparum malaria diagnostic strategy based on rapid diagnostic tests
      in returning travellers and migrants: a retrospective study.
AB  - BACKGROUND: Rapid diagnostic tests for malaria (RDTs) allow accurate diagnosis
      and prompt treatment. Validation of their usefulness in travellers with fever was
      needed. The safety of a strategy to diagnose falciparum malaria based on RDT
      followed by immediate or delayed microscopy reading at first attendance was
      evaluated in one referral hospital in Switzerland. METHODS: A retrospective study
      was conducted in the outpatient clinic and emergency ward of University Hospital,
      covering a period of eight years (1999-2007). The study was conducted in the
      outpatient clinic and emergency ward of University Hospital. All adults suspected
      of malaria with a diagnostic test performed were included. RDT and microscopy as
      immediate tests were performed during working hours, and RDT as immediate test
      and delayed microscopy reading out of laboratory working hours. The main outcome
      measure was occurrence of specific complications in RDT negative and RDT positive
      adults. RESULTS: 2,139 patients were recruited. 1987 had both initial RDT and
      blood smear (BS) result negative. Among those, 2/1987 (0.1%) developed
      uncomplicated malaria with both RDT and BS positive on day 1 and day 6
      respectively. Among the 152 patients initially malaria positive, 137 had both RDT
      and BS positive, four only BS positive and five only RDT positive (PCR confirmed)
      (six had only one test performed). None of the four initially RDT negative/BS
      positive and none of the five initially BS negative/RDT positive developed severe
      malaria while 6/137 of both RDT and BS positive did so. The use of RDT allowed a
      reduction of a median of 2.1 hours to get a first malaria test result.
      CONCLUSIONS: A malaria diagnostic strategy based on RDTs and a delayed BS is safe
      in non-immune populations, and shortens the time to first malaria test result.

PMID- 23158020
TI  - Dietary risk factors for the development of insulin resistance in adolescent
      girls: a 3-year prospective study.
AB  - OBJECTIVE: Identifying risk factors for insulin resistance in adolescence could
      provide valuable information for early prevention. The study sought to identify
      risk factors for changes in insulin resistance and fasting blood glucose levels.
      DESIGN: Prospective cohort of girls participating in the National Heart, Lung,
      and Blood Institute Growth and Health Study. SETTING USA SUBJECTS: Adolescent
      girls (n 774) assessed at the ages of 16-17 and 18-19 years. Over a 3-year
      period, measurements of fasting blood glucose and insulin and serum cotinine were
      taken, and dietary intake (3 d food diary), smoking status and physical activity
      levels were self-reported. RESULTS: Improvements in homeostasis model assessment
      of insulin resistance (HOMA-IR) were associated with increases in the percentage
      of energy intake from polyunsaturated fats (beta = -3.33, 95% CI -6.28, -0.39, P
      = 0.03) and grams of soluble fibre (beta = -5.20, 95% CI -9.81, -0.59, P = 0.03)
      between the ages of 16-17 and 18-19 years; with similar findings for insulin.
      Transitioning into obesity was associated with an increase in insulin (beta =
      6.34, 95% CI 2.78, 9.91, P < 0.001) and HOMA-IR (beta = 28.77, 95% CI 8.13,
      49.40, P = 0.006). Serum cotinine concentrations at 16-17 years, indicating
      exposure to tobacco, were associated with large increases (beta = 15.43, 95% CI
      6.09, 24.77, P < 0.001) in fasting blood glucose concentrations. CONCLUSIONS:
      Increases in the percentage of energy from polyunsaturated fat and fibre, and
      avoidance of excess weight gain and tobacco exposure, could substantially reduce
      the risk of insulin resistance in late adolescence.

PMID- 23158021
TI  - Clinical trial registration in physiotherapy journals: recommendations from the
      International Society of Physiotherapy Journal Editors.

PMID- 23158022
TI  - Validity of surface markers placement on the cervical spine for craniocervical
      posture assessment.
AB  - The objective of this study was to evaluate the ability of a physical therapist
      to place surface markers on the skin over spinous process of C2, C4, C6, and C7
      by evaluating the markers positioning using radiographs. A total of 39 healthy
      female subjects participated. From 39 subjects, 22 had 2 radiographs taken and 17
      had 1 radiograph taken. This study presents the results from the 22 subjects and
      from all 39 subjects together. The markers used were visible on the radiographs.
      The surface markers placement was tested by using percentage agreement. The
      criteria used were based on the direction of palpation. Only the markers placed
      that presented the center of the markers tip aligned to the tip of the spinous
      process was considered an acceptable placement. Only one level of agreement was
      considered. A misplaced marker was measured by its relation with the vertebra
      above or below. From the 22 subjects, the total percentage of agreement was
      87.5%. Of the 12.5% error, 1.7% (3) occurred attempting to find C2; 4.5% (8) for
      C4; 3.4% (6) for C6; and 2.8% (5) for C7. From the total of 39 subjects, the
      total percentage of agreement was 87.8%. Of the 12.2% error 1.3% (2) occurred
      attempting to find C2; 2.6% (4) for C4; 3.2% (5) for C6; and 5.2% (8) for C7.
      Based on the results from this study, clinicians and researchers should take into
      account possible errors on surface markers placement on the cervical spine when
      measuring craniocervical posture using photographs.

PMID- 23158023
TI  - Antioxidant defense system and family environment in adolescents with family
      history of psychosis.
AB  - BACKGROUND: Our objective was to determine antioxidant defence activity in
      healthy controls (HC) and healthy unaffected second-degree relatives of patients
      with early onset psychosis (HC-FHP), and to assess its relationship with familiar
      environment measured using the Family Environment Scale (FES). METHODS: We
      included 82 HC and 14 HC-FHP aged between 9 and 17 years. Total antioxidant
      status, lipid peroxidation, antioxidant enzyme activities and glutathione levels
      were determined in blood samples. RESULTS: There was a significant decrease in
      the total antioxidant level in the HC-FHP group compared with the HC group (OR =
      2.94; p = 0.009), but no between-group differences in the Global Assessment of
      Functioning (GAF) scale scores. For the FES, the HC-FHP group had significantly
      higher scores in the cohesion (p = 0.007) and intellectual-cultural dimensions
      (p=0.025). After adjusting for these two FES dimensions, total antioxidant status
      remained significantly different between groups (OR = 10.86, p = 0.009).
      CONCLUSIONS: Although causal relationships cannot be assumed, we can state that
      family environment is not playing a role in inducing oxidative stress in these
      healthy subjects. It could be hypothesized that families with affected relatives
      protect themselves from psychosis with positive environmental factors such as
      cohesion and intellectual-cultural activities.

PMID- 23158024
TI  - Delayed diagnosis of hypothyroidism following excision of a thyroglossal duct
      cyst.
AB  - Thyroglossal duct cysts can contain ectopic thyroid tissue, and in some cases
      this tissue may be the only functional thyroid gland. We present the case of a 6
      year-old girl with delayed diagnosis of iatrogenic hypothyroidism that developed
      after excision of a thyroglossal duct cyst.

PMID- 23158025
TI  - Distinguishing deficiencies in the steroidogenic acute regulatory protein and the
      cholesterol side chain cleavage enzyme causing neonatal adrenal failure.
AB  - OBJECTIVES: To determine the genetic basis of disordered steroidogenesis in
      Kuwaiti siblings. STUDY DESIGN: Two siblings (46,XX and 46,XY) had normal female
      external genitalia and severe glucocorticoid and mineralocorticoid deficiency
      presenting in the first month of life. Abdominal ultrasonography showed normal
      size adrenal glands, suggesting cholesterol side chain cleavage enzyme (P450scc)
      deficiency. The CYP11A1 gene encoding P450scc and the STAR gene encoding the
      steroidogenic acute regulatory protein (StAR) were directly sequenced from
      leukocyte DNA. RESULTS: All exons and intron/exon boundaries of the CYP11A1 gene
      were normal; the STAR gene was homozygous for a novel 14-base deletion/frameshift
      in exon 4 (g.4643_4656del), so that no functional protein could be produced. Both
      parents and an unaffected sibling were heterozygous; zygosity was confirmed with
      a BsmF1 restriction fragment length polymorphism. CONCLUSIONS: Unlike most
      patients with StAR deficiency, our patients did not have the massive adrenal
      hyperplasia typical of congenital lipoid adrenal hyperplasia. The distinction
      between StAR and P450scc deficiency may require gene sequencing.

PMID- 23158026
TI  - Impaired language abilities and white matter abnormalities in children born very
      preterm and/or very low birth weight.
AB  - OBJECTIVES: To investigate language abilities in children born very preterm (VPT;
      <32 weeks' gestational age) or very low birth weight (VLBW; <1500 g) at 7 years
      of age and compare their performances with children born at term, and to
      determine whether group differences could be explained by cerebral white matter
      abnormality on neonatal magnetic resonance imaging. STUDY DESIGN: A cohort of 198
      children born <30 weeks' gestational age and/or <1250 g, and 70 term controls
      were examined. White matter abnormalities were rated quantitatively on brain
      magnetic resonance imaging at term-equivalent age. Language was assessed at age 7
      years using standardized language tests. Differences between groups were tested
      in the 5 language subdomains of phonological awareness, semantics, grammar,
      discourse, and pragmatics. A mediation effect was tested between birth group,
      white matter abnormality, and language subdomains. RESULTS: The VPT/VLBW group
      performed significantly worse than controls on all language subdomains (all P <
      .001). White matter abnormality mediated the effect of group differences on
      phonological awareness, and partly mediated this effect for semantics, grammar,
      and discourse. White matter abnormality was not significantly associated with
      pragmatics (P = .13). CONCLUSIONS: Language is an important area of concern in
      children born VPT/VLBW. Neonatal white matter abnormality is an important
      predictor of outcome; however, different language abilities are differentially
      associated with neonatal white matter abnormality.

PMID- 23158027
TI  - Postraumatic frontal sinus obliteration with calvarial bone dust and
      demineralized bone matrix: a long term prospective study and literature review.
AB  - Defining the ideal material for frontal sinus obliteration remains controversial.
      Autogenous cancellous bone is effective because of its biological properties: it
      undergoes fast revascularization acting as an active scaffold for bone healing,
      but is linked to additional donor site morbidity. Bone dust harvesting from the
      skull surface produces no sequelae but availability is limited. Many efforts have
      been made to overcome these drawbacks, and an ideal bone substitute sought.
      Demineralized Bone Matrix (DBX; Musculoskeletal Transplant Foundation, Edison,
      NJ, USA) is a commercially available product composed of demineralized bone
      particles reduced after proper processing of human bone in combination with
      sodium hyaluronate. It generates an osteoconductive surface and it is also a
      source of osteoinductive factors. Radiological follow-up using computed
      tomography is a very reliable method of following-up ossification and detecting
      the early signs of possible complications. The authors present their clinical
      series of postraumatic frontal sinus obliteration using a mixture of calvarial
      bone dust and DBX shell, with long-term radiological monitoring. The technique
      was demonstrated to be effective, reliable, stable in the long term and
      associated with minimal morbidity.

PMID- 23158028
TI  - Do erupted third molars weaken the mandibular angle after trauma to the chin
      region? A 3D finite element study.
AB  - It has been suggested that third molars increase mandibular fragility because
      they do not contribute to its strength. For ethical reasons, a human study design
      that would permit the elucidation of this interference is not possible. This
      study evaluated the impact of the presence of erupted third molars on the
      mandibular angle of resistance when submitted to trauma. A three-dimensional (3D)
      mandibular model was obtained through finite element methodology using computed
      tomography (CT) with the geometry and mechanical properties to reproduce a normal
      mandibular structure. Human mandibles with no, one or two erupted third molars
      were evaluated. Whenever the third molar was present there was a greater
      concentration of tensions around the cervical part of its alveolus. Approximated
      Von Mises equivalent stress of the third molar region was 107.035 MPa in the
      mandible with teeth and 64.6948 MPa in the mandible without teeth. In the
      condylar region it was 151.65 MPa when the third molar was present and 184.496
      MPa when it was absent. The digital models created proved that the mandibular
      angle becomes more fragile in the presence of third molars. When they are absent
      the energy concentrates on the lateral e posterior aspect of the condylar neck.

PMID- 23158029
TI  - Study protocol: Intensive Care Anxiety and Emotional Recovery (Icare)-a
      prospective study.
AB  - BACKGROUND: Survivors of intensive care units (ICUs) commonly present with
      symptoms of anxiety, depression and post-traumatic stress disorder (PTSD) during
      recovery. A number of factors have been identified as predictors of these adverse
      emotional outcomes, but the role of state anxiety during critical illness in the
      development of these emotional problems remains unknown. PURPOSE: The Intensive
      Care Anxiety and Emotional Recovery (ICARe) study protocol proposes the
      development of a statistical model to determine the relationship between state
      anxiety during ICU stay and symptoms of anxiety, depression and PTSD at three
      occasions; after ICU discharge but prior to hospital discharge and at the third
      and sixth months post ICU discharge. METHODS: Prospective study including adult
      patients admitted to the ICU of a tertiary metropolitan Australian hospital for
      >=24 h who are able to: (1) communicate verbally or nonverbally; (2) understand
      English and (3) open their eyes spontaneously or in response to voice to respond
      to the Faces Anxiety Scale (state anxiety assessment). One hundred and seventy
      patients will be assessed for their levels of state anxiety during their ICU stay
      to achieve a sample size of about 104 patients six months after discharge. The
      outcomes of the ICARe study will include symptoms of anxiety, depression and PTSD
      assessed by standardised questionnaires widely used in intensive care research.
      Demographic, clinical, and social support information will also be collected.
      RESULTS: The projected sample size will provide sufficient power to evaluate the
      association between state anxiety and adverse emotional outcomes, as well as a
      variety of variables that will be entered into a multivariate regression
      analysis. CONCLUSION: This study will provide new evidence to improve care during
      critical illness and reduce adverse outcomes during recovery with the potential
      to decrease unnecessary suffering, promote comfort and improve long-term
      recovery.

PMID- 23158030
TI  - Renin inhibition in portal hypertension: novel indication beyond cardiovascular
      diseases?

PMID- 23158031
TI  - Aspirin resistance and ischemic stroke outcome: fact or fiction?

PMID- 23158032
TI  - Neonatal air leak syndrome and the role of high-frequency ventilation in its
      prevention.
AB  - Air leak syndrome includes pulmonary interstitial emphysema, pneumothorax,
      pneumomediastinum, pneumopericardium, pneumoperitoneum, subcutaneous emphysema,
      and systemic air embolism. The most common cause of air leak syndrome in neonates
      is inadequate mechanical ventilation of the fragile and immature lungs. The
      incidence of air leaks in newborns is inversely related to the birth weight of
      the infants, especially in very-low-birth-weight and meconium-aspirated infants.
      When the air leak is asymptomatic and the infant is not mechanically ventilated,
      there is usually no specific treatment. Emergent needle aspiration and/or tube
      drainage are necessary in managing tension pneumothorax or pneumopericardium with
      cardiac tamponade. To prevent air leak syndrome, gentle ventilation with low
      pressure, low tidal volume, low inspiratory time, high rate, and judicious use of
      positive end expiratory pressure are the keys to caring for mechanically
      ventilated infants. Both high-frequency oscillatory ventilation (HFOV) and high
      frequency jet ventilation (HFJV) can provide adequate gas exchange using
      extremely low tidal volume and supraphysiologic rate in neonates with acute
      pulmonary dysfunction, and they are considered to have the potential to reduce
      the risks of air leak syndrome in neonates. However, there is still no conclusive
      evidence that HFOV or HFJV can help to reduce new air leaks in published neonatal
      clinical trials. In conclusion, neonatal air leaks may present as a thoracic
      emergency requiring emergent intervention. To prevent air leak syndrome, gentle
      ventilations are key to caring for ventilated infants. There is insufficient
      evidence showing the role of HFOV and HFJV in the prevention or reduction of new
      air leaks in newborn infants, so further investigation will be necessary for
      future applications.

PMID- 23158033
TI  - The relationship between gallbladder status and recurrent biliary complications
      in patients with choledocholithiasis following endoscopic treatment.
AB  - BACKGROUND: Endoscopic methods are currently the treatment of choice for patients
      with common bile duct (CBD) stones, but subsequent management of the intact
      gallbladder for patients following endoscopic treatment is still controversial.
      The primary aim of this study was to discover the association between gallbladder
      status and recurrent biliary complications for patients with CBD stones after
      endoscopic treatment. Additionally, we also sought to determine risk factors for
      recurrent biliary complications in these patients. METHODS: The records of 1625
      patients with CBD stones following endoscopic treatment were reviewed. A total of
      681 patients were enrolled and subsequently categorized into four groups: Group 1
      (n = 201), calculous gallbladder; Group 2 (n = 140), acalculous gallbladder;
      Group 3 (n = 175), elective cholecystectomy after endoscopic treatment; and Group
      4 (n = 165), prior cholecystectomy. The basic demographics and recurrent biliary
      complications during follow-up among these four groups were analyzed by Chi
      square test, ANOVA, Kaplan-Meier analysis, and log-rank test. RESULTS: During the
      median follow-up period of 34 months, 133 patients (20%) with recurrent biliary
      complications were identified. The recurrence rates of Groups 1, 2, 3, and 4 were
      29%, 11%, 15%, and 19%, respectively. Kaplan-Meier analysis showed that patients
      with calculous gallbladder had a significantly higher rate of recurrent biliary
      complication. In multivariate analysis, patients with a history of cirrhosis,
      juxta-papillary diverticulum, calculous gallbladder, CBD size >= 1.5 cm, and
      endoscopic management with endoscopic sphincterotomy were at a higher risk for
      developing biliary complications (p = 0.029, p = 0.039, p < 0.001, p = 0.002, p =
      0.021, respectively.) CONCLUSION: Patients with cholecystolithiasis and CBD
      stones had a higher incidence of recurrent biliary complications. For some of
      these patients, elective cholecystectomy following endoscopic treatment may be
      considered. However, routine elective cholecystectomy in patients with normal
      gallbladder is not appropriate because of the low recurrence of biliary
      complications. Whether gallbladder function affects the biliary clearance and
      biliary complications requires further research.

PMID- 23158034
TI  - Utilization of statins and aspirin among patients with diabetes and
      hyperlipidemia: Taiwan, 1998-2006.
AB  - BACKGROUND: The proper use of statins and aspirin decrease the risk of coronary
      heart disease (CHD) among patients with diabetes (DM) and hyperlipidemia. The
      purpose of this study was to analyze the time trends and determinants of
      prescribing statins and aspirin among patients with DM and hyperlipidemia in
      medical practice in Taiwan. METHODS: A cohort of 21,667 patients with DM and
      hyperlipidemia during the period from 1998 to 2006 was identified by using data
      of ambulatory care claims from Taiwan's National Health Insurance Database. The
      dataset was categorized into two equal calendar periods: Period 1 (September 1998
      June 2002) and Period 2 (July 2002-April 2006). Multivariate logistic regression
      analyses were used to determine the independent determinants associated with
      receipt of lipid-lowering agents and aspirin among these patients. RESULTS: There
      were significant increases in the prescribing of statins (OR 1.78; 95% CI 1.66
      1.91) and aspirin (OR 1.47, 95% CI 1.50-1.59) in Period 2 as compared with Period
      1. Nevertheless, 30% of patients with coexisting CHD neither received statins nor
      aspirin. Only 15% to 25% of DM patients with hyperlipidemia and CHD received the
      combined treatment with aspirin and statin. In multivariate logistic regression,
      we found that women received aspirin less frequently than men. Old patients (>45
      years) with concomitant CHD were more likely to receive statins and aspirin.
      CONCLUSION: Despite the increasing trend in the use of statins and aspirin in DM
      patients with hyperlipidemia in Taiwan, the improvements were at best modest,
      particularly for secondary prevention. Our data indicate the need for continued
      efforts to improve the utilization of these drugs in daily practice.

PMID- 23158035
TI  - Number of involved lymph nodes is important in the prediction of prognosis for
      primary duodenal adenocarcinoma.
AB  - BACKGROUND: The significance of lymph node involvement regarding the prognosis of
      primary duodenal adenocarcinoma remains controversial. This study aims to
      evaluate the prognostic accuracy of nodal metastasis using the seventh edition
      American Joint Committee on Cancer staging system in patients with primary
      duodenal adenocarcinoma. METHODS: Between 1993 and 2010, 36 patients who had
      undergone surgical resection for primary duodenal adenocarcinoma at the Kaohsiung
      Veterans General Hospital were retrospectively reviewed. RESULTS: The median
      disease-free survival for all patients was 19 months and the median overall
      survival was 21 months. Lymph node metastases were found in 26 (72%) of the
      patients, and 14 patients (39%) patients had in excess of three positive lymph
      nodes (N2). Patients with N2 disease had significantly reduced overall survival,
      as compared to patients with three or fewer positive lymph nodes (N1; p = 0.036).
      In univariate analysis, factors including age >75 years, body weight loss, tumor
      size <= 4 cm, N2 disease and lymph node ratio >0.4 predicted shorter overall
      survival. Multivariate analysis demonstrated that N2 and lymph node ratio >0.4
      are significant risk factors associated with overall survival (p = 0.026 and p =
      0.042 respectively). N2 is also the only independent predictive factor for
      disease-free survival (p = 0.023). CONCLUSION: Subdivision of metastatic lymph
      nodes into N1 and N2 improves predictive ability. The seventh edition American
      Joint Committee on Cancer staging system is applicable in the present study with
      regard to the prediction of the prognosis for primary duodenal adenocarcinoma.

PMID- 23158036
TI  - Direct measurement of the signal intensity of diffusion-weighted magnetic
      resonance imaging for preoperative grading and treatment guidance for brain
      gliomas.
AB  - BACKGROUND: Magnetic resonance diffusion-weighted imaging (DWI) has been widely
      used clinically in imaging diagnosis of intracranial disorders. The purpose of
      current study was to present a quantitative method of direct measuring the DWI
      signal intensity of brain gliomas on the monitors of hospital picture archiving
      and communicating system (PACS) for grading gliomas. METHODS: This study
      recruited 135 patients with treatment-naive brain gliomas. Direct measurement of
      the signal intensity of selected tumoral regions of interest (ROIs) by DWI on the
      monitors of the hospital PACS was performed for all patients. From the
      measurements, we obtained three values, defined as DWI(T) (tumor), DWI(N) (the
      homologous normal-appearing area of the tumor ROI in the contralateral
      hemisphere), and DWI(WM) (normal-appearing white matter) in the contralateral
      frontal lobe. Two ratios, DWI(T/WM) and DWI(T/N), were obtained for each tumoral
      ROI. The same method was used for apparent diffusion coefficient (ADC) ratios of
      the tumoral ROI. Fractional polynomial regression and the Mann-Whitney U test
      were applied to determine the correlation between tumor grading, MIB-1 labeling
      index, and DWI and ADC ratios. Logistic regression models and receiver operating
      characteristic curve analysis were used to establish diagnostic models.
      Measurements of intraobserver and interobserver agreement were also made at 1
      month interval. RESULTS: The DWI ratios correlated positively with tumor grade
      and MIB-1 value (p < 0.01). Cut-off ratios of 1.62 for DWI(T/WM) and 1.47 for
      DWI(T/N) generated the optimal combination of sensitivity (0.82, 0.80),
      specificity (0.79, 0.86), and sound discriminating power, with an area under the
      curve of 0.87 and 0.84, respectively, to differentiate low-grade from high-grade
      gliomas. ADC ratios showed relatively worse sensitivity, specificity, and
      discriminating power than DWI ratios. Almost all intraobserver and interobserver
      measurements were within 95% agreement. CONCLUSION: The proposed method - direct
      measuring of tumor signal intensity of DWI on PACS monitors - is feasible for
      grading gliomas in clinical neuro-oncology imaging services and has a high level
      of reliability and reproducibility.

PMID- 23158037
TI  - Sonographic presentations of metaplastic breast cancers.
AB  - BACKGROUND: Metaplastic carcinoma of the breast (MPCB) is a rare breast cancer.
      We reviewed sonographic findings for MPCB. METHODS: Grayscale ultrasonography
      (US), color Doppler US (CDUS), and spectral Doppler US (SDUS) findings for 10
      patients with MPCB breast were retrospectively reviewed. RESULTS: The prevalence
      of MPCB was 3.9% among cases of breast cancer in our hospital. All patients had a
      rapidly growing palpable breast mass. The mean lesion size was 5.7 cm. On US, the
      lesion shape was most commonly gently lobulated (90%); only one showed an
      irregular shape (10%). The lesion shape was most commonly circumscribed (90%).
      Nine tumors had an abrupt boundary and one had an indistinct boundary. Lesion
      echogenicity was hypoechoic and very hypoechoic (40%), hypoechoic (30%), or very
      hypoechoic, hypoechoic, and hyperechoic (30%). All our cases had cystic parts
      with posterior acoustic enhancement, representing necrosis or hemorrhage. CDUS
      showed peripheral, central and marginal color flow signals. The resistivity index
      (RI) of tumor vessels in the lesions ranged from 0.7 to 1.3. The axillary lymph
      nodes were enlarged on US and were positive for metastasis in three cases (30%).
      CONCLUSION: MPCB is a rare rapidly growing tumor. US findings included gently
      lobulated, complex mass lesion with cystic parts and posterior acoustic
      enhancement, representing necrosis or hemorrhage. Increased color flow signals
      and relative high RI of the feeding arteries were also seen.

PMID- 23158038
TI  - Joint replacement in human immunodeficiency virus-infected patients.
AB  - BACKGROUND: Human immunodeficiency virus (HIV)-infected patients are at risk for
      bacterial and opportunistic infections with worsening immunosuppression. METHODS:
      From June 2000 to January 2009, six patients who were diagnosed with HIV
      infection underwent 10 joint replacement procedures, including six total hip
      arthroplasties, two total knee arthroplasties, and one shoulder hemiarthroplasty.
      An ordinary dose of postsurgical-empirical antibiotics was prescribed, with an
      average follow-up period of 38.6 months. All prostheses of total knee
      arthroplasty and shoulder hemiarthroplasty were fixed with vancomycin-impregnated
      bone cement. RESULTS: The rate of postoperative infection for HIV infected
      patients is supposed to be higher than for HIV negative patients. However, in our
      institution, there have been no HIV- positive patients who have suffered
      postoperative infection. CONCLUSION: HIV-positive patients can have excellent
      outcomes after undergoing various arthroplastic surgeries. This revelation,
      coupled with the advances in antiviral therapy that have helped to lengthen HIV
      patient lifespans, strongly suggests that these patients should receive
      arthroplastic surgery.

PMID- 23158039
TI  - The effect of virtual reality-enhanced driving protocol in patients following
      spinal cord injury.
AB  - BACKGROUND: Ability to drive was an important factor of quality of life for
      subjects with spinal cord injuries (SCI). However, the effect of virtual reality
      (VR) environment on driving ability and simulation-based driving training of
      people with SCI has not yet been investigated in any systematic, objective study.
      The purpose of this study was to examine the effect of the virtual reality
      created by a driving simulator, and determine the number of simulator sessions
      necessary for patients with spinal cord injuries to reach maximum driving
      competence. METHODS: This was a longitudinal, prospective before-after trial. It
      was comprised of 12 spinal cord injury patients who attended driving
      rehabilitation between July and December 2005. At their initial and subsequent
      evaluations, the participants' driving skills were measured as they drove along a
      simulated 6 km two- and three-lane urban road with traffic signals, overpass,
      underpass, obstacles, and a number of straight and curved stretches of road. The
      primary outcome measures consisted of total driving time, average speed, center
      line violation, stop-line violation, collisions, and steering/braking stability,
      with a sampling rate of 16 Hz. Each training session lasted for 30 minutes and
      was carried out twice a week for about 1.5 months. RESULTS: After 5 sessions of
      simulator driving training, there was a significant increase in the average speed
      and/or total driving time. The participants could stop their cars more precisely
      at the stop-line in traffic signal testing, and there was significantly less
      speed variation and center line violation in overpass testing. CONCLUSION: This
      study shows the significant effect of a virtual environment on the progress of
      driving rehabilitation, and suggests that incorporating virtual reality into
      rehabilitation programs will accelerate the maximal recovery of the patient's
      driving competence.

PMID- 23158040
TI  - Mediastinal diffuse large B-cell lymphoma invading the left atrium mimicking
      coronary artery disease with a mural thrombus.
AB  - A left atrial mass associated with coronary artery disease is often diagnosed as
      a mural thrombus rather than other possible etiologies such as benign primary
      cardiac tumor (myxoma, lipoma), a malignant primary cardiac tumor (sarcoma,
      lymphoma), or secondary involvement for extracardiac tumors. Malignant lymphoma
      initially presenting as intracardiac masses is very rare. Chest computed
      tomography with contrast enhancement and cardiac magnetic resonance may be the
      best methods for distinguishing primary cardiac tumors from direct extension from
      adjacent mediastinal structures. We report the case of a 59-year-old man with
      incidentally found mediastinal diffuse large B-cell lymphoma invading the left
      atrium, which presented with coronary artery disease and a left atrial mass.
      Improvement in cardiac ventricular function heart after coronary artery bypass
      grafting may provide the patient with a better chance of receiving an adequate
      dose of chemotherapy.

PMID- 23158041
TI  - Intracranial subdural hematoma coexisting with improvement in spontaneous
      intracranial hypotension after an epidural blood patch.
AB  - A 36-year-old male had spontaneous intracranial hypotension (SIH) presenting with
      refractory headache for 4 months. Multiple epidural blood patches (EBPs) yielded
      relief of symptoms, but the course was complicated, with asymptomatic
      intracranial subdural hematoma (SDH). Except for SDH, other radiological
      diagnostic signs of SIH were resolved and the patient's headaches improved after
      EBP. Owing to a mass effect and persistent cerebrospinal fluid (CSF) leakage,
      surgical repair of the spinal leakage was performed, but no cranial procedures
      were carried out. Postoperatively, the SDH completely resolved, but there was
      still CSF leakage at the level where surgery was performed. The patient has
      remained free of headache or other events for 3 years. It was reduction rather
      than elimination of the spinal CSF leak that yielded remission of SIH. In
      summary, intracranial SDH can be a complication of inadequately treated SIH (i.e.
      persistent minor CSF leakage). Management of SDH should focus on correction of
      the underlying SIH rather than craniotomy for hematoma evacuation.

PMID- 23158042
TI  - Glenoid screw position in the Encore Reverse Shoulder Prosthesis: an anatomic
      dissection study of screw relationship to surrounding structures.
AB  - BACKGROUND: Fixation of the baseplate to the glenoid for the Reverse Shoulder
      Prosthesis (DJO Surgical, Austin, TX, USA) requires secure screw purchase to
      avoid excessive micromotion and baseplate failure. The best screw length for
      fixation is unknown. In addition, excessively long screws or a plunge of the
      drill bit during baseplate insertion could injure surrounding structures.
      METHODS: Reverse Shoulder Prosthesis baseplates were inserted in 10 fresh-frozen
      shoulders by use of a 6.5-mm central screw and four 5.0-mm peripheral locking
      screws placed 90 degrees  to the baseplate. The top superior screw was placed
      into the base of the coracoid, corresponding to the 1-o'clock position in a right
      shoulder. The distances to surrounding vital structures were recorded, screws
      were removed, and screw hole lengths were measured to determine the most
      effective lengths in different parts of the glenoid scapula. RESULTS: The screw
      length was 30 mm for the superior screw holes, 28 mm for the inferior screw
      holes, 13 mm for the anterior screw holes, and 15 mm for the posterior screw
      holes. The central screw trajectory was through the anterior cortex. The anterior
      screw trajectory violated the subscapularis belly in all specimens. The posterior
      screw touched the suprascapular nerve or artery in 3 of 10 specimens. DISCUSSION:
      The superior and inferior screws have the longest bony fixation. Drill bit plunge
      during placement of the anterior screw poses a risk to the subscapularis muscle.
      Drilling for the posterior screw risks injury to the suprascapular nerve and
      artery at the spinoglenoid notch. CONCLUSIONS: The posterior screw should be
      placed with care to avoid neurovascular complications.

PMID- 23158043
TI  - Intra- and inter-rater reliability of the detection of tears of the supraspinatus
      central tendon on MRI by shoulder surgeons.
AB  - BACKGROUND: The purpose of this study was to determine the intra- and inter-rater
      reliability of detecting full- and partial-thickness tears of the supraspinatus
      intramuscular central tendon on magnetic resonance imaging (MRI) by orthopaedic
      shoulder surgeons. Full-thickness tears of this tendon have previously been
      associated with the failure of nonsurgical management of rotator cuff tears.
      METHODS: Shoulder MRIs from 40 patients entered into a prospective rotator cuff
      disease database were independently reviewed by two musculoskeletal (MSK)
      radiologists in order to determine if there was a partial- or full-thickness tear
      of the supraspinatus central tendon. The MRIs were randomly sorted and
      distributed to 16 fellowship-trained shoulder surgeons. The surgeons then
      similarly diagnosed each patient. After a 1-month interval, surgeons repeated the
      evaluation with the same set of randomly reordered MRIs. Surgeon intra- and inter
      rater reliability was determined with the kappa statistic. Agreement and inter
      rater reliability were also determined between the shoulder surgeons and MSK
      radiologists. RESULTS: For full-thickness tears, the intra-rater reliability was
      excellent (0.86 +/- 0.1, 95% confidence interval (CI): 0.81, 0.91) and the
      agreement was 93.4% +/- 4.6, 95% CI: 91.1, 95.8. Inter-rater reliability for both
      rounds was also excellent (0.77 and 0.74). The agreement between the shoulder
      surgeons and MSK radiologists was 92.9% +/- 3.9, 95% CI: 90.9, 94.9, and the
      kappa was 0.85 +/- 0.08, 95% CI: 0.81, 0.89. Including partial-thickness tears
      resulted in agreement of 65-92% and kappa values of 0.59-0.72. CONCLUSION: The
      reliability for the MRI detection of full thickness tears of the supraspinatus
      central tendon among shoulder surgeons and between shoulder surgeons and MSK
      radiologists was excellent.

PMID- 23158044
TI  - Adsorption study of CO2, CH4, N2, and H2O on an interwoven copper carboxylate
      metal-organic framework (MOF-14).
AB  - Metal-organic frameworks (MOFs) are attractive microporous materials for
      adsorption separations due to their extraordinary structures and impressive high
      surface areas. Catenation, or framework interpenetration, can significantly
      impact the crystal stability and improve the adsorption interactions. This
      interesting approach was used to obtain
      {[Cu(3)(BTB)(2)(H(2)O)(3)].(DMF)(9)(H(2)O)(2)} (MOF-14) as a microporous material
      with a high surface area and large pore volume, which are desirable parameters
      for adsorption applications. Here, we report a detailed study of this catenated
      material with its gas adsorption properties. The potential for adsorption
      separations is evaluated by measuring pure-component adsorption isotherms for
      carbon dioxide, methane, and nitrogen. The Ideal Adsorbed Solution Theory (IAST)
      was used to evaluate adsorption selectivities of MOF-14 for CO(2)/CH(4) and
      CO(2)/N(2) equimolar mixtures. In addition, water adsorption and the impact of
      exposure on structural degradation are reported. Compared to other open-metal
      site MOFs, MOF-14 adsorbs significantly less water. This interwoven MOF is a
      promising competitor to other MOF materials in the gas separation field due to
      low interactions with water and high selectivity for CO(2) over N(2).

PMID- 23158045
TI  - Letter from the editor: "ageENTs of change".

PMID- 23158046
TI  - Letter from the guest editor: head and neck imaging.

PMID- 23158047
TI  - Head and neck emergencies.

PMID- 23158048
TI  - Imaging of the paranasal sinuses.

PMID- 23158049
TI  - Diseases of the sella and parasellar region: an overview.

PMID- 23158050
TI  - Imaging of the temporal bone: a symptom-based approach.
AB  - Some of the symptoms associated with the temporal bone diseases are nonspecific,
      whereas others overlap with each other. Careful history and physical examination
      is of paramount importance for the localization of these disorders to a certain
      anatomic structure. Imaging plays a critical role in diagnosis, treatment
      planning, and follow-up of diseases of the temporal bone. This article discusses
      the common diseases associated with the temporal bone in a symptom-based
      approach. The categories reviewed are otalgia, hearing loss, tinnitus, and
      vertigo. Representative imaging features of the common abnormalities in each
      category are discussed. When a disease is associated with more than one symptom,
      it is included under the predominant symptom. We also provide guidelines for the
      preferred imaging modalities in certain clinical scenarios.

PMID- 23158051
TI  - Imaging of the salivary glands.

PMID- 23158052
TI  - Head and neck cancer.
AB  - Cross sectional imaging fills a crucial role in the work up of squamous cell
      cancer of the head and neck. The radiologist can suggest important considerations
      in treatment planning and disease prognosis. Key areas of anatomy in radiologic
      staging are reviewed.

PMID- 23158053
TI  - Imaging of thyroid and parathyroid glands.

PMID- 23158054
TI  - Cross-sectional survey of older patients' views regarding multidisciplinary care
      for chronic conditions in general practice.
AB  - The ageing population and increasing prevalence of chronic illness have
      contributed to the need for significant primary care reform, including increased
      use of multidisciplinary care and task substitution. This cross-sectional study
      explores conditions under which older patients would accept having health
      professionals other than their general practitioner (GP) involved in their care
      for chronic disease management (CDM). Ten practices were randomly sampled from a
      contiguous major city and inner regional area. Questionnaires were distributed to
      consecutive patients aged 60 years and over in each practice. Agency theory was
      used to inform analyses. Statistical analysis was undertaken using Wald's test,
      growth modelling and linear regression, controlling for the clustered design. The
      response rate was 53% (n=272). Most respondents (79%) had at least one chronic
      health condition. Respondents were more comfortable with GP than with practice
      nurse management in the CDM scenario (Wald's test=105.49, P<0.001). Comfort with
      practice nurse CDM was positively associated with increased contact with their GP
      at the time of the visit (beta=0.41, P<0.001), negatively associated with the
      number of the respondent's chronic conditions (beta=-0.13, P=0.030) and not
      associated with the frequency of other health professional visits. Agency theory
      suggests that patients employ continuity of care to optimise factors important in
      CDM: information symmetry and goal alignment. Our findings are consistent with
      the theory and lend support to ensuring that interpersonal continuity of care is
      not lost in health care reform. Further research exploring patients' acceptance
      of differing systems of care is required. 

PMID- 23158055
TI  - Cardiac output measurements using the bioreactance technique in critically ill
      patients.
AB  - Measurement of cardiac output (CO) using minimally invasive devices has gained
      popularity. In 11 patients we compared CO values obtained using the bioreactance
      technique--a new continuous, totally non-invasive CO monitor--with those obtained
      by semi-continuous thermodilution using a pulmonary artery catheter. We obtained
      CO measurements at study inclusion and after any relevant change in hemodynamic
      status (spontaneous or during fluid challenge, inotrope or vasopressor
      infusions). There was a poor correlation between the two techniques (r = 0.145).
      These data suggest that caution should be applied when using bioreactance devices
      in critically ill patients.

PMID- 23158056
TI  - Health status and health behaviour as predictors of the occurrence of
      unemployment and prolonged unemployment.
AB  - OBJECTIVES: Earlier research on health-related selection into unemployment has
      been based on relatively severe health problems, leaves questions unanswered
      about particular problems, follow-up times have been short and the measurement of
      unemployment utilised has been crude. The present study explores the effects of
      suboptimal health on employment in the long term, with statistics that enable
      assessment of the occurrence and extent of unemployment. STUDY DESIGN: Employment
      status of a population cohort (n = 1083) was measured half-yearly from 18 to 42
      years of age with four follow-up surveys. METHODS: Health status at 30 years of
      age was assessed with nine indicators. Their associations with the occurrence of
      a period of unemployment during the subsequent 12 years were analysed with Cox
      proportional hazard models, and generalized linear models were applied in
      assessing their associations with prolonged unemployment. RESULTS: Suboptimal
      self-rated health and suboptimal mood were the most robust predictors of both
      occurrence of unemployment {hazard rates 1.48 [95% confidence interval (CI) 1.13
      1.94] and 1.59 (95% CI 1.19-2.12), respectively} and prolonged unemployment [risk
      ratios 1.95 (95% CI 1.66-2.29) and 1.44 (95% CI 1.24-1.67), respectively].
      Significant associations, particularly with prolonged unemployment, were also
      seen for musculoskeletal pain, suboptimal sense functions and sleep quality, and
      smoking and risky alcohol intake. CONCLUSIONS: There is health-related selection
      into unemployment in early middle age, irrespective of unemployment earlier in
      the life course. High risk ratios for prolonged unemployment suggest that
      selection takes place, in particular, at re-employment. The findings indicate the
      need for policies to prevent those with a history of health problems being at a
      disadvantage in terms of future employment.

PMID- 23158057
TI  - Adolescent mothers and older mothers: who is at higher risk for adverse birth
      outcomes?
AB  - OBJECTIVES: To document the patterns of first-order fertility rates associated
      with extreme maternal ages in Taiwan; determine if there is a gap in adverse
      birth outcomes (specifically low birth weight and prematurity) between adolescent
      mothers and older mothers; and determine which factors are important in
      explaining the differences in adverse birth outcomes between adolescent mothers
      and older mothers. STUDY DESIGN: Government statistics and survey data [Taiwan
      Birth Cohort Survey (TBCS)]. METHODS: Descriptive statistics and logistic
      regression. RESULTS: Between 1989 and 2009, the first-order fertility rate for
      mothers aged 15-19 years decreased, whereas that for mothers aged 35-49 years
      increased. Analysis of TBCS data revealed that, in comparison with older mothers,
      adolescent mothers are not necessarily at higher risk for adverse birth outcomes.
      Birth complications, pregnancy-related risks, adequate number of prenatal care
      visits and weight gain are more important than socio-economic status and
      prevalence of smoking in determining birth outcomes among first-time mothers of
      extreme reproductive ages. Adolescent mothers are less likely to have birth
      complications and pregnancy-related risks, but are more likely to have an
      inadequate number of prenatal care visits and to gain an inadequate amount of
      weight compared with older mothers. CONCLUSIONS: The risks associated with
      adolescent mothers are easier to manage than the risks associated with older
      mothers. Their birth outcomes can be improved through good policy. Taiwan's
      health policy should target specific risks to reduce the number of adverse birth
      outcomes among adolescent mothers rather than try to prevent all childbearing
      during adolescence.

PMID- 23158058
TI  - Biopsy specimens obtained 7 days after starting chemoradiotherapy (CRT) provide
      reliable predictors of response to CRT for rectal cancer.
AB  - PURPOSE: Preoperative chemoradiation therapy (CRT) significantly decreases local
      recurrence in locally advanced rectal cancer. Various biomarkers in biopsy
      specimens obtained before CRT have been proposed as predictors of response.
      However, reliable biomarkers remain to be established. METHODS AND MATERIALS: The
      study group comprised 101 consecutive patients with locally advanced rectal
      cancer who received preoperative CRT with oral uracil/tegafur (UFT) or S-1. We
      evaluated histologic findings on hematoxylin and eosin (H&E) staining and
      immunohistochemical expressions of Ki67, p53, p21, and apoptosis in biopsy
      specimens obtained before CRT and 7 days after starting CRT. These findings were
      contrasted with the histologic response and the degree of tumor shrinkage.
      RESULTS: In biopsy specimens obtained before CRT, histologic marked regression
      according to the Japanese Classification of Colorectal Carcinoma (JCCC) criteria
      and the degree of tumor shrinkage on barium enema examination (BE) were
      significantly greater in patients with p21-positive tumors than in those with p21
      negative tumors (P=.04 and P<.01, respectively). In biopsy specimens obtained 7
      days after starting CRT, pathologic complete response, histologic marked
      regression according to both the tumor regression criteria and JCCC criteria, and
      T downstaging were significantly greater in patients with apoptosis-positive and
      p21-positive tumors than in those with apoptosis-negative (P<.01, P=.02, P=.01,
      and P<.01, respectively) or p21-negative tumors (P=.03, P<.01, P<.01, and P=.02,
      respectively). The degree of tumor shrinkage on both BE as well as MRI was
      significantly greater in patients with apoptosis-positive and with p21-positive
      tumors than in those with apoptosis-negative or p21-negative tumors,
      respectively. Histologic changes in H&E-stained biopsy specimens 7 days after
      starting CRT significantly correlated with pathologic complete response and
      marked regression on both JCCC and tumor regression criteria, as well as with
      tumor shrinkage on BE and MRI (P<.01, P<.01, P<.01, P<.01, and P=.03,
      respectively). CONCLUSIONS: Immunohistochemical expressions of p21 and apoptosis
      together with histologic changes on H&E-stained biopsy specimens obtained 7 days
      after starting CRT are strong predictors of the response to CRT.

PMID- 23158059
TI  - Chromosome damage and cell proliferation rates in in vitro irradiated whole blood
      as markers of late radiation toxicity after radiation therapy to the prostate.
AB  - PURPOSE: In vitro irradiated blood samples from prostate cancer patients showing
      late normal tissue damage were examined for lymphocyte response by measuring
      chromosomal aberrations and proliferation rate. METHODS AND MATERIALS: Patients
      were selected from a randomized trial evaluating the optimal timing of dose
      escalated radiation and short-course androgen deprivation therapy. Of 438
      patients, 3% experienced grade 3 late radiation proctitis and were considered to
      be radiosensitive. Blood samples were taken from 10 of these patients along with
      20 matched samples from patients with grade 0 proctitis. The samples were
      irradiated at 6 Gy and, along with control samples, were analyzed for dicentric
      chromosomes and excess fragments per cell. Cells in first and second metaphase
      were also enumerated to determine the lymphocyte proliferation rate. RESULTS: At
      6 Gy, there were statistically significant differences between the radiosensitive
      and control cohorts for 3 endpoints: the mean number of dicentric chromosomes per
      cell (3.26 +/- 0.31, 2.91 +/- 0.32; P=.0258), the mean number of excess fragments
      per cell (2.27 +/- 0.23, 1.43 +/- 0.37; P<.0001), and the proportion of cells in
      second metaphase (0.27 +/- 0.10, 0.46 +/- 0.09; P=.0007). CONCLUSIONS: These
      results may be a valuable indicator for identifying radiosensitive patients and
      for tailoring radiation therapy.

PMID- 23158061
TI  - An unusual cause of death: spontaneous urinary bladder perforation.
AB  - Spontaneous urinary bladder perforation is a rare and life-threatening condition
      similar to traumatic and iatrogenic perforation. The connection with the
      underlying bladder damage due to previous radiotherapy, inflammation, malignancy,
      obstruction, or other causes can be found in almost all cases. The symptoms are
      often nonspecific, and misdiagnosis is common. Here, we present a case of
      spontaneous urinary bladder perforation due to bladder necrosis in a diabetic
      woman. She presented to the emergency department with abdominal pain. Exploratory
      laparotomy was performed by surgeons and revealed necrosis of the anterior and
      lateral walls of the urinary bladder. Microscopic examination revealed necrotic
      changes throughout the bladder wall. Ghost-like cellular outlines were compatible
      with coagulative necrosis. Clusters of bacteria were also present in some
      necrobiotic tissues. Malignant cells were not present. It appears probable that
      the infection was due to local interference with the blood supply (arterial,
      capillary, or venous) combined with the systemic metabolic upset that led to the
      bladder condition. In our case, we observed partial necrosis of the bladder
      rather than distortion of the entire blood supply to the bladder as consequences
      of the microvascular effects of diabetes. Urinary bladder perforation must be
      considered in the differential diagnosis of patients presenting with free fluid
      in the abdomen/peritonitis, decreased urine output, and hematuria, and in whom
      increased levels of urea/creatinine are detected in serum and/ or peritoneal
      fluid aspirate.

PMID- 23158062
TI  - Traumatic floating clavicle.
AB  - We report a case of traumatic floating clavicula in a man aged 21 years. He was
      admitted to our emergency department with polytrauma sustained in a motor car
      accident, successfully treated 21 days after the accident with bipolar open
      reduction and wire stabilization.

PMID- 23158063
TI  - [Pulmonary hypertension in idiopathic pulmonary fibrosis].

PMID- 23158064
TI  - [Idiopathic pulmonary fibrosis and pulmonary embolism].

PMID- 23158065
TI  - [Idiopathic pulmonary fibrosis and lung cancer].

PMID- 23158066
TI  - [The phenotype of Th17 cells in sarcoidosis and its correlation with
      glucocorticoid therapy].
AB  - OBJECTIVE: To describe the characteristic of Th17 cells in peripheral blood (PB)
      and bronchoalveolar lavage fluid (BALF) from patients with sarcoidosis, and to
      investigate the effect of glucocorticoid therapy on the expression of RORgammat
      mRNA, and therefore to explore the role of Th17 cells in the immunopathogenesis
      of pulmonary sarcoidosis. METHODS: Ten patients with active pulmonary sarcoidosis
      who were prescribed with prednisone according to the guidelines were defined as
      the study group. All of them had positive pathological results and had definite
      response to corticosteroids. Ten healthy controls were recruited from volunteers
      with similar sex distribution and age. The proportion of CD(4)(+)IL-17A(+)T cells
      in peripheral blood mononuclear cells (PBMC) and BALF were calculated by flow
      cytometry. The mRNA expression of RORc in PBMC was measured by Real-time PCR.
      RESULTS: The mean age was (52 +/- 8) years in both the study group and the
      controls, and there were 9 females and 1 male in both groups. The proportion of
      CD(4)(+)IL-17A(+)T cells was higher in the PB of sarcoidosis patients compared to
      that of the controls [(1.61 +/- 1.09)% vs (0.51 +/- 0.43)%, t = 3.02, P = 0.014].
      For the same patients, the proportion of CD(4)(+)IL-17A(+)T cells was higher in
      the BALF compared to that in the PB [(3.05 +/- 1.87)% vs (1.61 +/- 1.09)%, t =
      2.94, P = 0.001]. After 4 to 6 week therapy with glucocorticoids, all the 10
      patients showed definite response. The level of RORc mRNA in the PB did not
      decrease significantly after treatment [(0.952 +/- 0.367) vs (0.168 +/- 0.272), t
      = 1.76, P = 0.057], although a trend was noted. CONCLUSIONS: Th17 cells was
      probably involved in the immunopathogenesis of sarcoidosis, and glucocorticoids
      might modulate the disturbance of Th17 cells in pulmonary sarcoidosis.

PMID- 23158067
TI  - [The effect of marrow mesenchymal stem cell transplantation on pulmonary fibrosis
      in rats].
AB  - OBJECTIVE: To study the possible mechanisms of marrow mesenchymal stem cells
      (MSC) in therapy of bleomycin (BLM)-induced pulmonary fibrosis in rats. METHODS:
      Fifty-four female Wistar rats were randomly divided into a control group, a BLM
      group and a MSC group. The control group received intratracheal normal saline,
      the BLM group received intratracheal instillation of bleomycin, and the MSC group
      was injected with male rat MSC solution of 0.5 ml (2.5*10(6) cells) via the tail
      vein after intratracheal instillation of bleomycin. Six rats from each group were
      killed on day 7, 14 and 28 of the experiments. BrdU labeling rate was measured
      before MSC transplantation. Lung tissue specimens were obtained for pathological
      examination, hydroxyproline content measurement, and detection of the expression
      of type II alveolar cell (ATII) specific marker-pulmonary surfactant protein-C
      (SP-C) in BrdU labeled MSC using dual immunofluorescence method. RT-PCR method
      was used to detect SP-C mRNA expression in the lung tissue and the bone marrow at
      different stages. The bone marrow mobilization involved in repair of type II
      alveolar cells after lung injury was observed. RESULTS: The final concentration
      of BrdU labeled MSC at 48 h was 10 umol/L, while the labeling efficiency was>98%,
      and the passage cells could be continuously labeled. In the MSC group, BrdU
      labeled MSCs with expression of SP-C were observed in all frozen sections of lung
      tissue at day 7, 14, and 28. By day 28, the lung fibrosis scores of the MSC group
      and the BLM group were (2.17 +/- 0.26) and (2.83 +/- 0.24), respectively, the
      lung tissue hydroxyproline contents were (138 +/- 21) mg/g and (184 +/- 19) mg/g,
      respectively, and the lung tissue SP-C mRNA expressions were (0.98 +/- 0.15) and
      (0.59 +/- 0.14), respectively. For both groups the SP-C mRNA expressions in the
      bone marrow at different stages were significantly increased as compared to the
      control group. CONCLUSIONS: Marrow mesenchymal stem cells could be transplanted
      into lung tissues of rats, and transformed into type II alveolar cells and was
      shown to prevent the development of pulmonary fibrosis. The damage-induced
      enhancement of host bone marrow mobilization was also involved in the repair
      process.

PMID- 23158068
TI  - [The prevalence of pulmonary tuberculosis in a national survey across China in
      2010].
AB  - OBJECTIVE: To investigate the epidemiological trend of pulmonary tuberculosis,
      and to provide scientific basis for making National Tuberculosis Control Program
      2011 - 2015. METHODS: Multi-stage stratified clustered sampling method was
      adopted, and 176 clusters were selected. All residents over 15 years old received
      interviewing and chest X-ray examination. Sputum smear and culture were done for
      subjects with abnormal X-ray films and symptoms suggestive of tuberculosis.
      Strains isolated by culture were further tested to identify Mycobacterium
      tuberculosis complex and non-tuberculosis mycobacteria. A weighted adjustment
      method accounting for complex sampling was used to calculate prevalence and 95%
      confidence intervals. Second-order Rao-Scott adjusted chi-square test was used to
      compare prevalence among different groups. RESULTS: The examination rate was
      96.1% (252 940/263 281) of the eligible people. The weighted prevalence of
      active, smear-positive, bacteriological positive pulmonary tuberculosis was
      459/100 000 (1310/252 940), 66/100 000 (188/252 940), 119/100 000 (347/252 940)
      respectively. Active, smear-positive, bacteriological positive pulmonary
      tuberculosis prevalence among people over 60 years were 1097/100 000 (637/57
      456), 177/100 000 (91/57 456), 323/100 000 (179/57 456). Active and
      bacteriological positive pulmonary tuberculosis prevalence in rural areas
      (569/100 000, 936/138 057; 153/100 000, 255/138 057) was higher than that in
      urban areas (307/100 000, 374/114 883; 73/100 000, 92/114 883). Prevalence in
      western provinces was high where the active, smear-positive, bacteriological
      positive pulmonary tuberculosis prevalence was 695/100 000 (567/69 896), 105/100
      000 (84/69 896), 198/100 000 (161/69 896) respectively. CONCLUSIONS: The epidemic
      of tuberculosis is still serious. Tuberculosis control work should be enhanced in
      high prevalence areas and high risk population.

PMID- 23158069
TI  - [Evaluation of tuberculin skin test conversion and interferon-gamma release assay
      in diagnosis of tuberculosis infection].
AB  - OBJECTIVE: To compare PPD conversion with gamma-interferon release assay (IGRA)
      in determining the newly Mycobacterium tuberculosis (MTB) infection during a TB
      outbreak. METHODS: The 505 subjects exposed to a TB outbreak were divided into 3
      groups based upon the induration diameters of PPD before the outbreak. The
      changes of PPD induration diameters were observed in different groups, and
      correlation between PPD conversion or IGRA and exposure levels were analyzed by
      logistic regression. RESULTS: In subjects with the highest exposure level, the
      increase in induration of PPD was (12 +/- 5) mm, (7 +/- 4) mm, and (5 +/- 3) mm
      respectively among the previous PPD < 5 mm, 5 - < 10 mm, and >= 10 mm groups, the
      difference being significant among groups, chi(2) = 43.12, P < 0.01. Using
      logistic regression analysis, PPD conversion was related to the exposure level
      (OR = 4.70, P < 0.05) only in the PPD < 5 mm group, while IGRA positivity was
      closely related to the exposure levels in all 3 groups (OR values were 2.16 -
      3.60, P < 0.05). In the high exposure group, the subjects with IGRA positivity
      combined with PPD conversion rate was 26.1% (31/119), and the subjects with IGRA
      positivity but no PPD conversion rate was 39.5% (47/119), while in the low
      exposure group the results were 6.5% (12/185) and 16.8% (31/185) respectively,
      the difference being significant (chi(2) = 22.82 and 19.63, P < 0.01). After 1
      year of follow-up, the reversion rate of the subjects with IGRA positivity was
      48.1% (91/189), while the mean increase value of PPD was (1.1 +/- 4.0) mm.
      CONCLUSION: IGRA is superior to PPD conversion in the diagnosis of tuberculosis
      infection, and more valuable in the detection of newly infected cases.

PMID- 23158070
TI  - [The negative enrichment by immunomagnetic beads for tumor cells from malignant
      pleural effusions].
AB  - OBJECTIVE: To establish a method (negative enrichment by immunomagnetic beads)
      for detection of tumor cells in pleural effusions and to evaluate the sensitivity
      and specificity of the method for clinical application. METHODS: Five, 10, 20, 50
      and 100 A549 (lung adenocarcinoma) cells were labeled with DAPI and added into 20
      ml pleural effusions [containing (1 - 10)*10(6)cells] from heart failure
      patients, followed by immunomagnetic negative enrichment method. Recovered cancer
      cells were enumerated using a fluorescent microscope. Tumor cells were enriched
      from pleural effusion samples by means of density gradient centrifugation and
      negative enrichment by immunomagnetic beads method, followed by identification
      with cytology analysis (Wright's Giemsa's staining), immunofluorescence staining
      (IF) and fluorescence in situ hybridization (FISH) using centromere DNA probes of
      chromosome 7 and 8. Cytology, IF and FISH evaluations were performed in 53
      pleural effusion samples, including 36 cases of malignant disease (25 male and 11
      female patients aging 40 to 78 years, mean age (63 +/- 9) and 17 cases of benign
      disease (8 male and 9 female patients aging 25 to 81 years, mean age (53 +/- 18).
      RESULTS: After DAPI staining and mixing with pleural effusions from heart failure
      patients, the cell recovery rates of A549 cells evaluated under fluorescence
      microscope were 75%, 78%, 82%, 85%, 88%, and the average recovery rate was 81.6%.
      Using negative enrichment method and density gradient centrifugation combined
      with cytology analysis, the positive rates of tumor cells in 36 malignant pleural
      effusion samples were 81% (29/36) and 61% (22/36), respectively (chi(2) = 4.00, P
      = 0.039). Using negative enrichment method combined with IF, the positive rate of
      CK18(+), DAPI(+), CD(45)(-) cells was 100%. Moreover, using negative enrichment
      method combined with FISH analysis, the positive rate of tumor cells was 86%
      (31/36), much higher than that using density gradient centrifugation combined
      with cytology analysis (chi(2) = 5.818, P = 0.012). In 17 cases of benign pleural
      effusions, using negative enrichment method combined with IF, the positive rate
      was 100%. But other methods didn't find cancer cells from benign pleural
      effusions. CONCLUSIONS: It was applicable to enrich tumor cells from pleural
      effusions using negative enrichment method by immunomagnetic beads. This method
      combined with cytology analysis or FISH significantly enhanced the sensitivity
      and specificity of tumor cell detection in pleural effusions. But it was
      difficult to distinguish cancer cells from mesothelial cells using
      immunofluorescence staining with CK18, DAPI and CD(45) label. More specific
      markers were needed to recognize tumor cells from pleural effusions.

PMID- 23158071
TI  - [Clear cell tumor of the lung: report of seven cases and literature review].
AB  - OBJECTIVE: To study the clinical characteristics, chest imaging, pathology,
      diagnosis and treatment of clear cell tumor of the lung (CCTL). METHODS: Seven
      cases of CCTL diagnosed from January 2000 to December 2010 in our hospital, and
      38 cases from literatures published in mainland of China, were retrospectively
      analyzed. RESULTS: The age of the patients was (44 +/- 18) years, with equal sex
      distribution. In most of the patients, the lesions were incidentally found during
      routine examinations. Chest roentgenogram or CT scan showed a homogenous, rounded
      opacity (solitary nodule) of (3.2 +/- 1.4) cm in diameter. Contrast-enhanced CT
      scans revealed a sign of intense enhancement because of these tumors were highly
      vascular, containing capillaries and sinusoidal vessels in some patients.
      Pathologic examination showed rounded and oval tumor cells with abundant clear
      cytoplasm, distinct cell borders, and cytoplasm rich in periodic acid Schiff
      positive glycogen granules. Immunohistochemically, CCTL expressed melanocytic and
      myogenic markers, such as human melanoma black-45 (HMB-45), HMSA-1 and actin. But
      its epithelial markers were negative. Resection via operation was the only
      effective method till now. CONCLUSIONS: CCTL is a rare benign tumor with special
      features of clinical characteristics, radiology and pathology. The diagnosis is
      based on distinct pathologic characteristics. Earlier operation with long term
      follow-up is recommended.

PMID- 23158072
TI  - [Pyopneumothorax caused by Salmonella choleraesuis: a case report and review of
      the literature].
AB  - OBJECTIVE: To improve understanding of the clinical features, diagnosis and
      treatment of pyopneumothorax caused by Salmonella choleraesuis. METHODS: One case
      of pyopneumothorax caused by Salmonella choleraesuis diagnosed and treated in our
      hospital in 2010 was reported and the related literatures were reviewed. As of
      May 2011, the literature review was carried out with "Salmonella choleraesuis"
      and "thoracic empyema" as the search terms in Wanfang Med Online and Pubmed
      Database. RESULTS: A 43-year-old Chinese woman presenting with fever and chest
      pain for 4 days was admitted to our hospital. A CT scan of the chest revealed a
      massive shadow with mixed density in the right hemithorax, from the top of thorax
      to diaphragmatic surface, and there was air inside or surrounding the mass
      irregularly but without an air-fluid level. Blood culture and bronchial secretion
      culture by bronchoscope both showed some serotypes of Salmonella strains. At
      first intravenous antibiotic therapy (piperacillin-tazobactam, ceftazidime, and
      then imipenem-cilastatin) was ineffective. Open chest surgery was performed, and
      chest tube placed. Salmonella choleraesuis was isolated from the drained pleural
      fluid. Chest tube drainage remained in place for more than 6 weeks, and with
      prolonged antibiotic therapy, which contributed to a good outcome. Literature
      review found no related reports in Wanfang Med Online, while 3 literatures were
      found in Pubmed, including 2 of case report and 1 of retrospective study. Among
      973 patients with empyema thoracis in the retrospective study, 12 of these
      patients, including 9 men and 3 women, were infected with Salmonella species. The
      median age was 49 years, and 10 patients were immunocompromised, including
      malignancy, liver cirrhosis, and diabetes mellitus. Seven patients were infected
      with Salmonella choleraesuis, and 4 (57%) of them died. CONCLUSIONS:
      Pyopneumothorax or thoracic empyema is a rare complication of Salmonella
      choleraesuis infection. Higher rates of death were noted in this disease.
      Salmonella choleraesuis infection is even more serious in adult patients with
      underlying diseases. Early diagnosis, appropriate antimicrobial drug therapy, and
      aggressive drainage are necessary to improve the outcome of patients with
      pyopneumothorax or thoracic empyema due to Salmonella choleraesuis.

PMID- 23158073
TI  - [Effects of long term nasal continuous positive airway pressure on the blood
      pressure of patients with obstructive sleep apnea hypopnea syndrome].
AB  - OBJECTIVE: To analyze the effects of long term nasal continuous positive airway
      pressure on the blood pressure of patients with OSAHS. METHODS: From April 1997
      to October 2008, 2898 patients from the First Affiliated Hospital of Fujian
      Medical University who complained snore during sleeping were studied. Nine
      hundred eighty cases were diagnosed as OSAHS with hypertension, and these
      patients were randomly divided into 2 groups: one group was treated with
      antihypertensive drugs and nasal continuous positive airway pressure (nCPAP),
      while the other group only received antihypertensive drugs. The polysomnography
      (PSG) was recorded during sleeping and the blood pressure was remeasured after 6
      months or more. All patients were followed up for 5 years to observe the long
      term effects of nCPAP or drugs. RESULTS: Systolic and diastolic blood pressure in
      the nCPAP group significantly decreased after 6 months [(125 +/- 16) mm Hg (1 mm
      Hg = 0.133 kPa) vs (136 +/- 19) mm Hg, (83 +/- 10) mm Hg vs (95 +/- 15) mm Hg, P
      < 0.05], and the decreasing extent of blood pressure in nCPAP group was more
      notable than antihypertensive drug group [decreasing extent of systolic blood
      pressure:(10 +/- 11) mm Hg vs (4 +/- 11) mm Hg; decreasing extent of diastolic
      blood pressure: (11 +/- 7) mm Hg vs (6 +/- 7) mm Hg; P < 0.05]. The total
      effective rate in nCPAP group was significantly higher than that in
      antihypertensive drug group (90% vs 38%, P < 0.01). One hundred and eighty three
      cases in nCPAP group and 157 cases in antihypertensive drug group completed the 5
      year follow-up and the blood pressure was controlled within the normal range.
      Some patients could gradually reduce or stop the use of antihypertensive drugs
      and the blood pressure didn't appear to rebound. The number of antihypertensive
      drugs in the nCPAP group was significantly fewer as compared to the
      antihypertensive drugs group after 2, 3, 4 and 5 years' follow-up. CONCLUSIONS:
      nCPAP is a safe and effective treatment for high blood pressure in patients with
      OSAHS.

PMID- 23158074
TI  - [Evaluation of carotid artery elasticity in patients with obstructive sleep apnea
      syndrome using quantitative arterial stiffness technique].
AB  - OBJECTIVE: To explore the changes and clinical value of carotid elasticity index
      in patients with obstructive sleep apnea syndrome (OSAS) by quantitative arterial
      stiffness (QAS) technique. METHODS: Seventy-two OSAS patients were divided into 2
      groups according to whether there was coexisting hypertension. Of them, there
      were 37 OSAS patients without hypertension (OSAS1 group) and 35 OSAS patients
      with hypertension (OSAS2 group). In addition, forty healthy volunteers were
      recruited as the normal control group. We measured the arterial elastic
      parameters including vascular expansibility (VE), compliance coefficient (CC),
      stiffness index (beta) and pulse wave velocity (PWV) through QAS analysis
      technique. The difference of the parameters among the groups was analyzed. In the
      OSAS group, polysomnograph (PSG) data were recorded and analyzed including apnea
      hypopnea index (AHI), minimal pulse oxyhemoglobin saturation (miniSpO(2)), time
      spent below oxygen saturation of 90% (Ts90%) and oxygen desaturation index (ODI).
      Correlations and regression were calculated between indices of oxygen saturation
      and PWV. RESULTS: Compared with normal control group, in OSAS1 and OSAS2 groups,
      VE and CC were significantly lower, but beta and PWV was significantly higher (P
      < 0.05). Compared with OSAS1 group, CC in OSAS2 group decreased but beta and PWV
      increased significantly (P < 0.05). In the OSAS group, PWV was correlated
      positively with systolic blood pressure, AHI, ODI and age (r = 0.285 - 0.542, all
      P < 0.05). Through stepwise multiple linear regression analysis, age and ODI were
      the significant variables to determine PWV. CONCLUSION: The decreases in arterial
      elasticity are present in OSAS patients. These changes are more evident in OSAS
      patients with hypertension. QAS technique plays an important role in analyzing
      the arterial elasticity accurately and could be used as a quantitative mean to
      evaluate early atherosclerosis.

PMID- 23158075
TI  - [Cigarette smoke exposure induced pulmonary artery pressure increase through
      inhibiting Kv1.5 and Kv2.1 mRNA expression in rat pulmonary artery smooth
      muscles].
AB  - OBJECTIVE: To investigate the effect of cigarette smoke exposure on Kv1.5 and
      Kv2.1 mRNA expression in rat pulmonary arterial smooth muscle cells (PASMCs), and
      further to clarify the possible mechanism of cigarette smoking induced pulmonary
      arterial hypertension. METHODS: Primary cell culture and animal experiments were
      used in this study. Rat distal PASMCs were isolated and cultured by collagenase
      digestion. PASMCs were treated by nicotine 100 nmol/L. After 48 h, Kv1.5 and
      Kv2.1 mRNA expression were detected by real-time quantitative PCR and compared
      with the control group. Rat model of chronic exposure to cigarette smoke was
      established. Thirty-six male SD rats were randomly divided equally into 6 groups:
      (1) 1 month control group; (2) 1 month cigarette exposure group; (3) 3 month
      control group; (4) 3 month cigarette exposure group; (5) 6 month control group;
      (6) 6 month cigarette exposure group. Direct right heart manometry, HE staining
      and real-time quantitative PCR were used to detect the effect of smoke exposure
      on rat right ventricular systolic pressure (RVSP), mean pressure (mPAP), right
      ventricular hypertrophy index [RV/(LV + S)] as well as Kv1.5 and Kv2.1 mRNA
      expression on pulmonary artery smooth muscle at different time points (1 month, 3
      months and 6 months). RESULTS: The mPAP and RVSP in cigarette smoke exposure 6
      month group were (13.08 +/- 0.64) mm Hg and (29.73 +/- 0.83) mm Hg, slightly
      higher than those in the control 6 month group [(10.16 +/- 0.44) mm Hg and (22.56
      +/- 0.64) mm Hg] (P < 0.01). The ratio of Kv1.5 mRNA expression in distal
      pulmonary arteries in 1 month, 3 month, 6 month cigarette exposure group to that
      in control groups was (52 +/- 11)%, (64 +/- 19)% and (75 +/- 11)% (P < 0.05). The
      ratio of Kv2.1 mRNA expression in distal pulmonary arteries in 1 month, 3 month,
      6 month cigarette exposure groups to that in control groups was (51.0 +/- 18.6)%,
      (78.7 +/- 10.1)% and (71.4 +/- 2.3)% (P < 0.01); Chronic exposure to cigarette
      smoke significantly decreased Kv1.5 and Kv2.1 mRNA expression in rat pulmonary
      arterial smooth muscle at each time point. The ratio of Kv1.5 and Kv2.1 mRNA
      expression in rat distal PASMCs treated with nicotine (100 nmol/L, 48 h) to
      control group were (62 +/- 14)% (P < 0.05) and (72 +/- 15)% (P < 0.01),
      respectively. Nicotine inhibited Kv1.5 and Kv2.1 mRNA expression in rat distal
      PASMCs. CONCLUSION: Cigarette smoke exposure may be involved in pulmonary
      hypertension by downregulating potassium channels Kv1.5 and Kv2.1 mRNA expression
      in rat pulmonary artery smooth muscles.

PMID- 23158076
TI  - [Mucin and interstitial lung disease].

PMID- 23158077
TI  - Preoperative therapy for localized prostate cancer: a comprehensive overview.
AB  - At the 2012 American Society of Clinical Oncology (ASCO) Annual Meeting, two
      studies of preoperative systemic therapy for localized prostate cancer garnered
      significant attention. In the first, investigators evaluated various permutations
      of conventional hormonal therapies prior to prostatectomy, with detailed
      biomarker studies focused on tissue androgens. In the second, investigators
      assessed the novel CYP17 lyase inhibitor abiraterone prior to prostatectomy. Both
      studies provide a wealth of biological information, but the question remains -
      will preoperative systemic therapy ultimately be incorporated into clinical
      algorithms for prostate cancer? Herein, the existing literature for both
      preoperative hormonal and chemotherapeutic approaches is reviewed. We performed a
      MEDLINE search of published prospective and retrospective clinical studies
      assessing preoperative systemic therapy for prostate cancer from 1982 onwards,
      revealing a total of 75 publications meeting these criteria. Of these, 55
      possessed a number of patients (i.e., greater than 10) deemed worth of the
      current analysis. Beyond outlining these datasets, we discuss the relevance of
      clinical and pathologic endpoints in assessing preoperative therapy.

PMID- 23158078
TI  - Fruits and vegetables intake and characteristics associated among adolescents
      from Southern Brazil.
AB  - BACKGROUND: Increased body weight has been associated with an unhealthy diet, low
      consumption of fruits and vegetables. Our objective was to investigate whether
      adolescents had low intake of fruits and vegetables, and whether gender, age and
      education could affect the feeding patterns. METHODS: A population-based sample
      of adolescents, aged 12-19 years, were randomly selected in southern Brazil and
      included in this cross-sectional study. The total daily consumption of fruits,
      vegetables, rice and beans were investigated in standardized household
      interviews, using a food frequency questionnaire and questions, being categorized
      as five or more servings per day as the five-a-day diet. ANOVA, ANCOVA, and
      modified Poisson regression were used in the analysis. RESULTS: Adolescents (n =
      568) were included, 49.5% boys, 14.3% had overweight and 8.8% obesity.
      Approximately 23% of participants consumed five daily servings of fruits and
      vegetables. It was observed that 36.7% of boys and 31.0% of girls consumed less
      than one serving of fruit per day, and 58.4% and 44.6%, respectively, consumed
      less than one serving of vegetables. The consumption of vegetables, fruits, and
      rice and beans were not independently associated with gender. Overweight was
      associated with higher intake of five-a-day, independently of confounding
      factors. CONCLUSIONS: Adolescents from southern Brazil have lower frequency of
      consumption of five servings a day of fruits and vegetables combined.

PMID- 23158079
TI  - Study of the betulin enriched birch bark extracts effects on human carcinoma
      cells and ear inflammation.
AB  - BACKGROUND: Pentacyclic triterpenes, mainly betulin and betulinic acid, are
      valuable anticancer agents found in the bark of birch tree. This study evaluates
      birch bark extracts for the active principles composition. RESULTS: New improved
      extraction methods were applied on the bark of Betula pendula in order to reach
      the maximum content in active principles. Extracts were analyzed by HPLC-MS,
      Raman, SERS and 13C NMR spectroscopy which revealed a very high yield of betulin
      (over 90%). Growth inhibiting effects were measured in vitro on four malignant
      human cell lines: A431 (skin epidermoid carcinoma), A2780 (ovarian carcinoma),
      HeLa (cervix adenocarcinoma) and MCF7 (breast adenocarcinoma), by means of MTT
      assay. All of the prepared bark extracts exerted a pronounced antiproliferative
      effect against human cancer cell lines. In vivo studies involved the anti
      inflammatory effect of birch extracts on TPA-induced model of inflammation in
      mice. CONCLUSIONS: The research revealed the efficacy of the extraction
      procedures as well as the antiproliferative and anti-inflammatory effects of
      birch extracts.

PMID- 23158080
TI  - Hygienic-dietary recommendations for major depression treatment: study protocol
      of a randomized controlled trial.
AB  - BACKGROUND: Depression is a highly prevalent and disabling mental disorder with
      an incidence rate which appears to be increasing in the developed world. This
      fact seems to be at least partially related to lifestyle factors. Some hygienic
      dietary measures have shown their efficacy as a coadjuvant of standard treatment.
      However, their effectiveness has not yet been proved enough in usual clinical
      practice. METHODS: Multicenter, randomized, controlled, two arm-parallel,
      clinical trial involving 300 patients over 18 years old with a diagnosis of Major
      Depression. Major depression will be diagnosed by means of the Mini-International
      Neuropsychiatric Interview. The Beck Depression Inventory total score at the end
      of the study will constitute the main efficacy outcome. Quality of Life and
      Social and Health Care Services Consumption Scales will be also administered.
      Patients will be assessed at three different occasions: baseline, 6-month follow
      up and 12-month follow-up. DISCUSSION: We expect the patients in the active
      lifestyle recommendations group to experience a greater improvement in their
      depressive symptoms and quality of life with lower socio-sanitary costs. TRIAL
      REGISTRATION: ISRCTN73931675.

PMID- 23158081
TI  - Endoscopic and robotic thyroidectomy for cancer.
AB  - This article focuses on endoscopic and robotic surgical techniques for the
      treatment of thyroid cancer. The most widely applied techniques are minimally
      invasive video-assisted thyroidectomy, as well as various combinations using a
      primarily axillary-based approach. Although there are few large studies
      delineating the benefits of endoscopic thyroid resection when compared with
      traditional thyroidectomy, in patients who desire the lack of a cervical
      incision, endoscopic thyroidectomy provides a safe and oncologically effective
      surgical option when applied by experienced surgeons. Endoscopic surgical
      treatment of thyroid disease is a developing field and deserves further study
      before widespread application.

PMID- 23158082
TI  - Minimally invasive surgery for esophageal cancer.
AB  - Minimally invasive surgery has revolutionized the surgical management of benign
      foregut disease, as well as pulmonary and other gastrointestinal malignancies.
      With the potential to reduce operative morbidity and increase patient
      satisfaction, minimally invasive esophagectomy for the management of esophageal
      cancer is gaining in popularity. It is unclear, however, whether the minimally
      invasive approach to esophageal cancer resection has comparable long-term
      oncologic results. This article discusses the rationale for minimally invasive
      esophagectomy, describes the surgical technique, and reviews the published
      results.

PMID- 23158083
TI  - Video-assisted thoracoscopic surgery lobectomy for lung cancer.
AB  - Surgical resection is currently the gold standard in operable patients with early
      stage lung cancer. Video-assisted thoracoscopic surgery (VATS) lobectomy is a
      technique that has technically evolved and grown increasingly popular over the
      past two decades. This article presents the evolution, definition, current
      application, and some of the controversies surrounding VATS lobectomy.

PMID- 23158084
TI  - Laparoscopic gastrectomy for cancer.
AB  - Gastric cancer is common worldwide. Tumor location and disease stage differ
      between Asian and Western countries. Western patients often have higher BMIs and
      comorbidities that may make laparoscopic resections challenging. Multiple trials
      from Asian countries demonstrate the benefits of laparoscopic gastrectomy for
      early gastric cancer while maintaining equivalent short-term and long-term
      oncologic outcomes compared with open surgery. The outcomes of laparoscopy seem
      to offer equivalent results to open surgery. In the United States, laparoscopic
      gastrectomy remains in its infancy and is somewhat controversial. This article
      summarizes the literature on the epidemiology, operative considerations and
      approaches, and outcomes for laparoscopic gastrectomy.

PMID- 23158085
TI  - Laparoscopic distal pancreatectomy.
AB  - The laparoscopic approach for benign and malignant lesions in the tail of the
      pancreas is becoming a more widely used approach. Multiple prospective studies
      have shown the feasibility and safety of laparoscopic distal pancreatectomy in
      single-center and multi-center settings. Laparoscopic distal pancreatectomy is a
      challenging procedure, because the pancreas is surrounded by critical structures
      and located in the retroperitoneum. Pancreatic fistula remains a common
      complication in the laparoscopic approach. Distal pancreatic aggressive tumors
      may not be appropriate for the laparoscopic approach due to the lack of oncologic
      safety studies.

PMID- 23158086
TI  - Laparoscopic resection of the liver for cancer.
AB  - Although most laparoscopic hepatic procedures are performed for benign disease,
      an increasing fraction is for malignant disease, including primary and metastatic
      liver tumors. Data suggest that minor and major hepatic resections are feasible
      and can be performed safely. The limited data currently available suggest that
      survival in patients with hepatocellular carcinoma and colorectal metastatic
      disease may be comparable to that achieved with open hepatectomy. The benefits of
      the laparoscopic approach seem to be shorter hospitalization, smaller incisions,
      and less blood loss. Despite the progress to date, concern continues about the
      potential for significant intraoperative hemorrhagic complications and oncologic
      outcomes.

PMID- 23158087
TI  - Technique, outcomes, and evolving role of extirpative laparoscopic and robotic
      surgery for renal cell carcinoma.
AB  - This article provides an overview of extirpative laparoscopic and robotic
      procedures used in the management of renal cell carcinoma, including laparoscopic
      radical nephrectomy, laparoscopic partial nephrectomy, and robotic-assisted
      partial nephrectomy. The clinical indications and principles of surgical
      technique for each of these procedures are discussed. The oncologic, renal
      functional, and perioperative outcomes of these procedures are also assessed and
      compared, as are complication rates.

PMID- 23158088
TI  - Laparoscopic adrenalectomy for cancer.
AB  - Laparoscopic procedures are preferred by surgeons and patients alike because of
      decreased pain, reduced perioperative morbidity, and an earlier return to self
      reliance. During the last decade, laparoscopic adrenalectomy has become the
      technique most commonly used for the removal of benign adrenal tumors. The
      indications for laparoscopy in malignant adrenal tumors remains controversial,
      because oncologic resections have not been reproducible compared with open
      techniques.

PMID- 23158089
TI  - Laparoscopic prostatectomy for prostate cancer: continued role in urology.
AB  - The purpose of this article is to provide an update on the current literature
      evaluating outcomes with laparoscopic prostatectomy. The reported perioperative,
      oncologic, and functional outcomes with this approach are reviewed and
      comparisons are made to the open and robotic-assisted approaches.

PMID- 23158090
TI  - Lap colectomy and robotics for colon cancer.
AB  - Robotic approaches have seen significant growth in the last 5 years. Taking
      advantage of three-dimensional visualization, improved articulation, and multiple
      operating arms provides theoretical and real advantages in colorectal cancer
      surgery. This article reviews the potential advantages and disadvantages, current
      outcomes, and future directions for robotic approaches to colon cancer surgery.

PMID- 23158091
TI  - Laparoscopic approaches in oncology. Foreword.

PMID- 23158092
TI  - Laparoscopic approaches in oncology.

PMID- 23158093
TI  - The Society of Hematologic Oncology (SOHO): moving forward in the battle against
      hematologic malignancies.

PMID- 23158094
TI  - The history of leukemia therapy--a personal journey.
AB  - The advances in leukemia therapy which occurred during one professional lifetime
      of the author is described, and forms the basis for projecting the probable
      progress which will occur in a subsequent professional lifetime. These advances
      in leukemia therapy have rapidly found application to 'solid tumors,' suggesting
      that the road to cancer control will be led by discoveries made in leukemia
      biology, treatment, and prevention.

PMID- 23158095
TI  - A systematic literature review and meta-analysis of radioimmunotherapy
      consolidation for patients with untreated follicular lymphoma.
AB  - BACKGROUND: Follicular lymphoma (FL) is characterized by multiple relapses and
      progressively shorter response durations with subsequent therapies. Despite the
      development of numerous treatment strategies to reduce the risk of progression,
      optimal therapeutic strategies for patients with FL remain undefined.
      Radioimmunotherapy (RIT) with an anti-CD20 antibody linked to iodine-131 or to
      yttrium-90 has emerged as well-tolerated treatment after induction. We conducted
      a systematic literature review and meta-analyses to quantify the benefits of
      consolidative RIT. METHODS: We searched the CENTRAL and MEDLINE libraries, and
      conference abstracts for reports on phase II/III clinical trials that assessed
      RIT consolidation for patients with untreated FL. Extracted data included
      pretreatment disease status, patient characteristics, treatment regimen, response
      rates, progression-free survival (PFS), and overall survival (OS). Pooled
      estimates of complete response (CR), overall response (OR), 2- and 5-year PFS and
      OS rates were computed by using random effects models. RESULTS: Eight studies (n
      = 783) were included in the meta-analyses. CR rates after RIT ranged from 69.0%
      to 96.5%, 2-year PFS ranged from 64.8% to 86.1%, and 5-year PFS ranged from 47.0%
      to 67.3%. The pooled estimates of the CR rate and OR rate were 82.7% (95% CI,
      67.4%-91.7%) and 96.2% (95% CI, 90.4%-98.6%), respectively. The pooled estimates
      for 5-year PFS and OS were 57.6% (95% CI, 47.8%-66.9%) and 90.1% (95% CI, 83.9%
      94.1%), respectively. CONCLUSIONS: We believe that these aggregated data can
      further the discussion on RIT as a consolidation therapy and inform decisions on
      future study designs Additional studies are needed to compare the benefits of RIT
      consolidation to maintenance therapy with rituximab.

PMID- 23158096
TI  - Carbamazepine, but not valproate, displays pharmacoresistance in lamotrigine
      resistant amygdala kindled rats.
AB  - The voltage gated sodium channel (VGSC) blocker lamotrigine (LTG), when
      administered during kindling acquisition, leads to the development of resistance
      to LTG. The present study aimed to assess whether LTG-resistant amygdala-kindled
      rats display subsequent resistance to the VGSC blocker carbamazepine (CBZ) and
      the broad-spectrum antiepileptic drug (AED) sodium valproate (VPA). Two groups of
      male Sprague Dawley rats received either 0.5% methylcellulose (MC) or LTG
      (5mg/kg, i.p.) 1h before each amygdala kindling stimulation. Treatments were
      stopped once both the groups were fully kindled. Two days later, both groups were
      challenged with a higher dose of LTG (15mg/kg, i.p.) to verify LTG-resistance in
      the experimental group (i.e., LTG-pretreated rats). The efficacy of CBZ and VPA
      was then evaluated in both groups. A higher dose of LTG blocked fully kindled
      seizures in the vehicle-treated rats but not seizures in the LTG-treated group.
      The mean seizure score, of the control group (1.2+/-0.3) was significantly lower
      (P<.05) than that of the LTG-treated population (3.5+/-0.7; n=8). A lower percent
      of the population in the control group was observed to display a generalized
      stage 4-5 seizure compared to the experimental group (i.e., those that received
      LTG during kindling acquisition) (28.5% vs. 62%, respectively). Interestingly,
      CBZ (10, 20, and 40mg/kg) displayed a dose-dependent anticonvulsant effect in the
      vehicle-kindled group, but was less effective in LTG-treated animals. In
      contrast, VPA (300mg/kg) effectively blocked the behavioral seizure and decreased
      the afterdischarge duration (ADD) in both vehicle and LTG groups. These findings
      suggest that the LTG-resistant, amygdala-kindled rat may represent a novel model
      of pharmacoresistant epilepsy.

PMID- 23158098
TI  - The Colorado Adoption Project.
AB  - This paper describes the Colorado Adoption Project (CAP), an ongoing genetically
      informative longitudinal study of behavioral development. We describe the
      features of the adoption design used in CAP, and discuss how this type of design
      uses data from both parent-offspring and related- versus unrelated-sibling
      comparisons to estimate the importance of genetic and shared environmental
      influences for resemblance among family members. The paper provides an overview
      of CAP's history, how subjects were ascertained, recruited, and retained, and the
      domains of assessment that have been explored since the CAP's initiation in 1975.
      Findings from some representative papers that make use of data from CAP
      participants illustrate the study's multifaceted nature as a parent-offspring and
      sibling behavioral genetic study, a study that parallels a complimentary twin
      study, a longitudinal study of development, a source of subjects for molecular
      genetic investigation, and a study of the outcomes of the adoption process
      itself. As subjects assessed first at age 1 approach age 40, we hope the CAP will
      establish itself as the first prospective adoption study of lifespan development.

PMID- 23158099
TI  - Robotic selective postganglionic thoracic sympathectomy for the treatment of
      hyperhidrosis.
AB  - BACKGROUND: The surgical management of hyperhidrosis is controversial. Robotic
      surgical systems with their high-definition magnified 3-dimensional view and
      increased maneuverability in a confined space may facilitate the technique of
      selective sympathectomy (ramicotomy). We present a case series of patients
      undergoing selective postganglionic thoracic sympathectomy using robotic
      technology. METHODS: This study is a case series analysis of patients who
      underwent selective postganglionic thoracic sympathectomy from July 2006 to
      November 2011. The operation was performed on a video-assisted thoracoscopic
      surgery (VATS) platform. The robot was used for pleural dissection and division
      of the postganglionic sympathetic fibers and the communicating rami. The success
      of sympathectomy was assessed by intraoperative temperature measurement of the
      ipsilateral upper extremity, patient interviews, and scoring of the symptomatic
      nature of hyperhidrosis based on the Hyperhidrosis Disease Severity Scale.
      RESULTS: There were 110 sympathectomies performed in 55 patients (25 men, 30
      women). Simultaneous bilateral sympathectomy was performed in all patients.
      Median age was 28 years (range, 16 to 65 years). There was no conversion to
      thoracotomy. Complications were minor and were seen in 5 of 55 patients (9%).
      There were no deaths. Median hospital stay was 1 day (range, 1 to 4 days). Of the
      55 patients, 53 (96%) had sustained relief of their hyperhidrosis at a median
      follow-up of 24 months (range, 3 to 36 months), and compensatory sweating was
      seen in 4 patients (7.2%). CONCLUSIONS: Robotic thoracoscopic selective
      sympathectomy is an effective, feasible, and safe procedure with excellent relief
      of hyperhidrosis and low rates of compensatory sweating and complications.

PMID- 23158100
TI  - Transcriptome analysis of primary monocytes shows global down-regulation of
      genetic networks in HIV viremic patients versus long-term non-progressors.
AB  - Despite significant contributions of monocytes to HIV persistence, the genomic
      basis of HIV-infection of monocytes and its association with plasma viremia
      remain elusive. To understand HIV interactions with monocytes during disease
      progression, monocytic transcriptomes from long-term non-progressors (LTNP), HIV+
      patients with viral load <1000, with viral load >1000, and seronegative controls
      were analyzed using Illumina microarray. Differentially expressed genes were
      identified (fold change >2; adjusted p<0.05) and GSEA between HIV+ groups
      demonstrated that the down-regulation of the pathways including Toll-like
      receptor (TLR) signaling, cytokine-cytokine receptor interaction, cell cycle and
      apoptosis was significantly associated with the viremic groups, whereas their up
      regulation with the LTNP group. The down-regulation of TLR pathway in the viremic
      patients was exemplified by the decreased expression of TLR with the subsequent
      tuning down of MAPK, NF-kappaB, JAK-STAT, and IRF cascades. These data provide
      the first transcriptomic distinction between HIV+ progressors and LTNPs based on
      primary monocytes.

PMID- 23158097
TI  - Review of Journal of Cardiovascular Magnetic Resonance 2011.
AB  - There were 83 articles published in the Journal of Cardiovascular Magnetic
      Resonance (JCMR) in 2011, which is an 11% increase in the number of articles
      since 2010. The quality of the submissions continues to increase. The editors had
      been delighted with the 2010 JCMR Impact Factor of 4.33, although this fell
      modestly to 3.72 for 2011. The impact factor undergoes natural variation
      according to citation rates of papers in the 2 years following publication, and
      is significantly influenced by highly cited papers such as official reports.
      However, we remain very pleased with the progress of the journal's impact over
      the last 5 years. Our acceptance rate is approximately 25%, and has been falling
      as the number of articles being submitted has been increasing. In accordance with
      Open-Access publishing, the JCMR articles go on-line as they are accepted with no
      collating of the articles into sections or special thematic issues. For this
      reason, the Editors feel it is useful to summarize the papers for the readership
      into broad areas of interest or theme, which we feel would be useful, so that
      areas of interest from the previous year can be reviewed in a single article in
      relation to each other and other recent JCMR articles. The papers are presented
      in broad themes and set in context with related literature and previously
      published JCMR papers to guide continuity of thought in the journal. We hope that
      you find the open-access system increases wider reading and citation of your
      papers, and that you will continue to send your quality manuscripts to JCMR for
      publication.

PMID- 23158102
TI  - HIV-1 pre-mRNA commitment to Rev mediated export through PSF and Matrin 3.
AB  - Human immunodeficiency virus gene expression and replication are regulated at
      several levels. Incompletely spliced viral RNAs and full-length genomic RNA
      contain the RRE element and are bound by the viral trans-acting protein Rev to be
      transported out of the nucleus. Previously we found that the nuclear matrix
      protein MATR3 was a cofactor of Rev-mediated RNA export. Here we show that the
      pleiotropic protein PSF binds viral RNA and is associated with MATR3. PSF is
      involved in the maintenance of a pool of RNA available for Rev activity. However,
      while Rev and PSF bind the viral pre-mRNA at the site of viral transcription,
      MATR3 interacts at a subsequent step. We propose that PSF and MATR3 define a
      novel pathway for RRE-containing HIV-1 RNAs that is hijacked by the viral Rev
      protein.

PMID- 23158103
TI  - [Autologous fat grafting to the postmastectomy irradiated chest wall prior to
      breast implant reconstruction: a series of 68 patients].
AB  - INTRODUCTION: After radiotherapy, breast reconstruction with an implant carries a
      high risk of failure and complication. Clinical and experimental studies have
      demonstrated that grafting adipose tissue (lipofilling) in an irradiated area
      enhances skin trophicity. Thus, we have started performing preliminary fat
      grafting to the irradiated chest wall prior to implant reconstruction in order to
      limit complications and failure risk. PATIENTS AND METHODS: Patients were
      included in this study from 2007 to 2011. All patients had had mastectomy and
      irradiation for breast cancer. They all had one or more sessions of lipofilling
      prior to breast implant reconstruction. These patients were prospectively
      followed up in order to collect the following data: postoperative complications;
      cosmetic result; local breast cancer recurrences. RESULTS: Sixty-eight patients
      were included. The mean number of fat grafting sessions was 2.3 (range 1-6). An
      average volume of 115mL (70-275) was injected each time. The mean volume of
      breast implants was 300mL (185-400). The mean follow-up was 23months (450). No
      breast cancer local recurrence was diagnosed during follow-up. Implant
      explantation was performed in one case (1.47%) The mean cosmetic result was
      4.5/5. CONCLUSION: Fat grafting to the irradiated chest wall prior to implant
      placement might be an alternative to flap reconstruction for patients who are not
      suitable or who refuse this option.

PMID- 23158104
TI  - Reducing barriers to testing for Chlamydia trachomatis by mailed self-collected
      samples.
AB  - BACKGROUND: Chlamydia trachomatis (chlamydia) is the most commonly notified
      sexually transmissible bacterial infection in Australia, where distance to health
      services can be a barrier. This study investigated the acceptability of a self
      collection kit for chlamydia testing (sent by mail) and assessed the risk
      profiles of participants with respect to locality. METHODS: In total, 2587 self
      collection kits were distributed opportunistically or sent directly to
      participants upon request, as was a self-administered questionnaire. RESULTS: The
      return rate was 13.2% (n=341) for samples and questionnaires. The return rate did
      not differ with location (P=0.522) but with mode of distribution (opportunistic:
      9.7%; by request: 27.4%; P<0.001). Although 37% of participants had previously
      been tested for chlamydia, 77.5% said that they would not have sought testing
      otherwise. The median age of participants was 22.6 years, 33.8% were male and
      9.1% were of Aboriginal descent. Overall, 9.0% (95% confidence interval (CI)=6.1
      12.5) of participants were chlamydia-positive. Prevalence of chlamydia and
      Aboriginal participation increased with remoteness (P<0.001), and self-reported
      condom use was significantly reduced for remote and very remote locations
      (P=0.008). Within remote and very remote locations, 30.8% (95% CI=9.1-61.4) of
      Aboriginal participants and 38.9% of non-Indigenous participants were chlamydia
      positive (P=0.718; 95% CI=17.3-64.3). DISCUSSION: Testing for chlamydia using a
      mailed self-collection kit opened access to a predominantly test-naive
      population. The proposed model was able to reach remote populations. Actively
      requested kits were more likely to be returned.

PMID- 23158101
TI  - Contribution of SAM and HD domains to retroviral restriction mediated by human
      SAMHD1.
AB  - The human SAMHD1 protein is a novel retroviral restriction factor expressed in
      myeloid cells. Previous work has correlated the deoxynucleotide
      triphosphohydrolase activity of SAMHD1 with its ability to block HIV-1 and
      SIV(mac) infection. SAMHD1 is comprised of the sterile alpha motif (SAM) and
      histidine-aspartic (HD) domains; however the contribution of these domains to
      retroviral restriction is not understood. Mutagenesis and deletion studies
      revealed that expression of the sole HD domain of SAMHD1 is sufficient to achieve
      potent restriction of HIV-1 and SIV(mac). We demonstrated that the HD domain of
      SAMHD1 is essential for the ability of SAMHD1 to oligomerize by using a
      biochemical assay. In agreement with previous observations, we mapped the RNA
      binding ability of SAMHD1 to the HD domain. We also demonstrated a direct
      interaction of SAMHD1 with RNA by using enzymatically-active purified SAMHD1
      protein from insect cells. Interestingly, we showed that double-stranded RNA
      inhibits the enzymatic activity of SAMHD1 in vitro suggesting the possibility
      that RNA from a pathogen might modulate the enzymatic activity of SAMHD1 in
      cells. By contrast, we found that the SAM domain is dispensable for retroviral
      restriction, oligomerization and RNA binding. Finally we tested the ability of
      SAMHD1 to block the infection of retroviruses other than HIV-1 and SIV(mac).
      These results showed that SAMHD1 blocks infection of HIV-2, feline
      immunodeficiency virus (FIV), bovine immunodeficiency virus (BIV), Equine
      infectious anemia virus (EIAV), N-tropic murine leukemia virus (N-MLV), and B
      tropic murine leukemia virus (B-MLV).

PMID- 23158105
TI  - Factors affecting healing of ankle fractures.
AB  - Ankle fractures have been widely described in orthopedic and podiatric studies.
      These injuries have been associated with significant patient morbidity,
      infection, malunion, nonunion, and arthritis. Avoiding complications and
      optimizing outcomes demands an awareness of the factors affecting the healing of
      ankle fractures. The prognosis of surgical treatment of these injuries has varied
      according to patient factors or injury severity, or a combination. Cigarette
      smoking, obesity, and diabetes are some of the factors linked to the prognosis of
      ankle fractures. We conducted a retrospective cohort study of 58 patients treated
      for an ankle fracture at a single center. The objective of the present study was
      to comprehensively evaluate the factors affecting the clinical outcome of
      surgically treated ankle fractures.

PMID- 23158106
TI  - Fluoroscopic method for localization of the anteromedial portal for use in ankle
      arthroscopy: technique tip.
AB  - Ankle arthroscopy has become a standard surgical technique for the treatment of
      many ankle pathologies. Over the past 30 years, the technique has undergone
      modification and standardization in order to improve surgical performance and
      outcomes. In contrast to the ankle joint, the hip joint is a deep joint, which
      makes visualization and palpation of the topographical anatomy quite difficult.
      The use of fluoroscopy has enabled the surgeon to successfully perform hip
      arthroscopy for the treatment of selective hip pathologies. Fluoroscopy also can
      improve the localization of the anteromedial portal for use in ankle arthroscopy.
      This technique is valuable for the less-experienced ankle arthroscopist, in
      resident education, and for the experienced arthroscopist when surface anatomy
      palpation and visualization is less than ideal due to soft tissue edema and
      obesity.

PMID- 23158107
TI  - Underlying synovial sarcoma in a patient with a history of complex regional pain
      syndrome: a case report.
AB  - Synovial sarcoma, although commonly found in the lower extremities, is considered
      a rare neoplasm. One of the distinguishing features of a synovial sarcoma is its
      initial benign features that can later turn into a more aggressive lesion.
      Because of the subtle early features, synovial sarcoma can be mistaken for other
      pathologic entities that present with clinical signs of erythema, warmth, edema,
      and pain. We present a patient who was originally diagnosed with complex regional
      pain syndrome. That diagnosis and subsequent treatment of complex regional pain
      syndrome likely delayed the appropriate evaluation, which led to a 9-month lag in
      the proper diagnosis. After magnetic resonance imaging and biopsy were performed,
      synovial sarcoma was diagnosed. The patient was referred to an orthopedic
      oncologist, who performed a transtibial amputation and chemotherapy. Although
      rare, neoplasm should always be considered in the differential diagnosis of a
      clinical presentation of a painful erythematous and edematous mass.

PMID- 23158108
TI  - Atherosclerosis: lessons from LXR and the intestine.
AB  - Modulation of the cholesterol-sensing liver X receptors (LXRs) and their
      downstream targets has emerged as promising therapeutic avenues in
      atherosclerosis. The intestine is important for its unique capabilities to act as
      a gatekeeper for cholesterol absorption and to participate in the process of
      cholesterol elimination in the feces and reverse cholesterol transport (RCT).
      Pharmacological and genetic intestine-specific LXR activation have been shown to
      protect against atherosclerosis. In this review we discuss the LXR-targeted
      molecular players in the enterocytes as well as the intestine-driven pathways
      contributing to cholesterol homeostasis with therapeutic potential as targets in
      the prevention and treatment of atherosclerosis..

PMID- 23158109
TI  - Effect of hypothermia and extracorporeal life support on drug disposition in
      neonates.
AB  - Extracorporeal membrane oxygenation (ECMO) is a valuable treatment modality in
      neonates with reversible cardiopulmonary failure in therapy-resistant pulmonary
      hypertension after perinatal asphyxia, septic shock or ECMO cardiopulmonary
      resuscitation. Neonates with severe perinatal asphyxia are currently treated with
      therapeutic hypothermia to improve neurological outcome. Consequently,
      therapeutic hypothermia may be indicated in the neonatal ECMO population. Both
      ECMO and hypothermia have been associated with changes in drug disposition.
      However, little is known about the combined effects of these treatment
      modalities. This review will explore the available literature, identify possible
      changes in pharmacokinetics and make suggestions for future research directions.

PMID- 23158110
TI  - Influence of prior sunlight exposure on ICU mortality--does delirium play a role?

PMID- 23158111
TI  - Raynaud phenomenon.

PMID- 23158112
TI  - The Group Oriented Arterial Leg Study (GOALS) to improve walking performance in
      patients with peripheral arterial disease.
AB  - People with lower extremity peripheral artery disease (PAD) have greater
      functional impairment and faster functional decline than those without PAD. We
      describe methods for the Group Oriented Arterial Leg Study (GOALS), an ongoing
      randomized controlled clinical trial designed to determine whether a Group
      Mediated Cognitive Behavioral (GMCB) intervention improves functional performance
      in PAD participants, compared to a health education control condition. In GOALS,
      PAD participants were randomized to either an intervention or a health education
      control condition in a parallel design. Both conditions consist of weekly group
      sessions with other PAD participants. In the intervention, cognitive behavioral
      techniques are used to assist participants in setting and adhering to home-based
      walking exercise goals. Participants are encouraged to walk for exercise at home
      at least 5 days/week. In the control condition, participants receive lectures on
      health-related topics. After 6 months of on-site weekly sessions, participants
      are transitioned to telephone follow-up for another 6 months. Participants in the
      intervention are asked to continue home walking exercise. The primary outcome is
      change in six-minute walk performance between baseline and six-month follow-up.
      Secondary outcomes include change in six-minute walk performance at 12-month
      follow-up, and change in treadmill walking performance, the Walking Impairment
      Questionnaire, quality of life, and physical activity at six and 12-month follow
      up. In conclusion, if our group-mediated cognitive behavioral intervention is
      associated with improved walking performance in individuals with PAD, results
      will have major public health implications for the large and growing number of
      people with PAD.

PMID- 23158113
TI  - Understanding differences in access and use of healthcare between international
      immigrants to Chile and the Chilean-born: a repeated cross-sectional population
      based study in Chile.
AB  - INTRODUCTION: International evidence indicates consistently lower rates of access
      and use of healthcare by international immigrants. Factors associated with this
      phenomenon vary significantly depending on the context. Some research into the
      health of immigrants has been conducted in Latin America, mostly from a
      qualitative perspective. This population-based study is the first quantitative
      study to explore healthcare provision entitlement and use of healthcare services
      by immigrants in Chile and compare them to the Chilean-born. METHODS: Data come
      from the nationally representative CASEN (Socioeconomic characterization of the
      population in Chile) surveys, conducted in 2006 and 2009. Self-reported
      immigrants were compared to the Chilean-born, by demographic characteristics
      (age, sex, urban/rural, household composition, ethnicity), socioeconomic status
      (SES: education, household income, contractual status), healthcare provision
      entitlement (public, private, other, none), and use of primary services. Weighted
      descriptive, stratified and adjusted regression models were used to analyse
      factors associated with access to and use of healthcare. RESULTS: There was an
      increase in self-reported immigrant status and in household income inequality
      among immigrants between 2006 and 2009. Over time there was a decrease in the
      rate of immigrants reporting no healthcare provision and an increase in reporting
      of private healthcare provision entitlement. Compared to the Chilean-born,
      immigrants reported higher rates of use of antenatal and gynaecological care,
      lower use of well-baby care, and no difference in the use of Pap smears or the
      number of attentions received in the last three months. Immigrants in the bottom
      income quintile were four times more likely to report no healthcare provision
      than their equivalent Chilean-born group (with different health needs, i.e.
      vertical inequity). Disabled immigrants were more likely to have no healthcare
      provision compared to the disabled Chilean-born (with similar health needs, i.e.
      horizontal inequity). Factors associated with immigrants' access to, and use of,
      healthcare were sex, urban/rural status, education and country of origin.
      CONCLUSION: There were significant associations between SES, and access to and
      use of healthcare among immigrants in Chile and a higher prevalence of no health
      care provision entitlement among poor and disabled immigrants compared to the
      Chilean-born. Changing associations between access and use of healthcare and SES
      among immigrants in Chile over time may reflect changes in their socio
      demographic composition or in the survey methodology between 2006 and 2009.

PMID- 23158114
TI  - Lithium, gray matter, and magnetic resonance imaging signal.
AB  - BACKGROUND: Magnetic resonance imaging studies have reported that lithium can
      increase the volume of gray matter in the human brain, a finding that has been
      ascribed to the established neurotrophic or neuroprotective effects of the drug.
      Lithium, however, might directly influence the intensity of the magnetic
      resonance signal so it is possible that the volumetric findings are artifactual,
      essentially a consequence of altered image contrast. METHODS: Anatomical and
      quantitative magnetic resonance scans were acquired on 31 healthy young men
      before and after taking either lithium or placebo for 11 days. Brain volume
      change was derived with two established techniques: voxel-based morphometry (a
      statistical approach using signal intensity to segment images into tissue types),
      and Structural Image Evaluation, using Normalization, of Atrophy (a technique
      that operates by detecting changes in the position of the boundaries of the
      brain). In a subgroup (n = 12), tissue-specific magnetic resonance relaxation
      times were compared before and after lithium with quantitative T1-mapping
      techniques. RESULTS: Voxel-based morphometry revealed that gray matter volume was
      increased by lithium but not placebo (p = .001), whereas Structural Image
      Evaluation, using Normalization, of Atrophy showed no difference between lithium
      and placebo (p = .23). Taking lithium reduced the T1 relaxation of the gray
      matter only (p = .008). CONCLUSION: Magnetic resonance images of the brain differ
      before and after lithium, but this difference might derive from a change in the
      characteristics of the signal rather than a tangible increase in volume.

PMID- 23158116
TI  - Sports medicine in China: a clinical review and update.

PMID- 23158115
TI  - The double edged T wave.

PMID- 23158117
TI  - Takotsubo cardiomyopathy or acute myocardial infarction?

PMID- 23158118
TI  - Orthopaedics and traumatology in China: current status and future.

PMID- 23158119
TI  - Traditional Chinese Medicine and orthopaedics-is there room for modern
      application?

PMID- 23158120
TI  - Comparison of adjacent segment degeneration five years after single level
      cervical fusion and cervical arthroplasty: a retrospective controlled study.
AB  - BACKGROUND: Cervical arthroplasty is indicated to preserve cervical motion and
      prevent accelerated adjacent segment degeneration. Whether accelerated adjacent
      segment degeneration is prevented in the long term is unclear. This trial
      compared adjacent segment degeneration in Bryan disc arthroplasty with that in
      anterior cervical decompression and fusion five years after the surgery. METHODS:
      We studied patients with single level degenerative cervical disc disease. The
      extent of adjacent segment degeneration was estimated from lateral X-rays.
      RESULTS: Twenty-six patients underwent single level Bryan disc arthroplasty and
      twenty-four patients underwent single level anterior cervical decompression and
      fusion. All patients were followed up for an average of sixty months. In the
      Bryan arthroplasty group, nine (17.6%) segments developed adjacent segment
      degeneration, which was significantly lower than that (60.4%) in the anterior
      cervical decompression and fusion group. Eleven segments in the Bryan
      arthroplasty group developed heterotopic ossification according to McAfee's
      classification and two segments had range of motion less than 2 degrees . In the
      heterotopic ossification group, four (19.5%) segments developed adjacent segment
      degeneration, similar to the number in the non-heterotopic ossification group
      (16.7%). Adjacent segment degeneration rate was 50% in grade IV group but 11.8%
      in grade II to III. CONCLUSIONS: Adjacent segment degeneration was accelerated
      after anterior cervical decompression and fusion. However, Bryan disc
      arthroplasty avoided accelerated adjacent segment degeneration by preserving
      motion. Patients with grade IV heterotopic ossification lost motion, and the rate
      of adjacent segment degeneration was higher than that in patients without
      heterotopic ossification.

PMID- 23158121
TI  - Comparison of Topping-off and posterior lumbar interbody fusion surgery in lumbar
      degenerative disease: a retrospective study.
AB  - BACKGROUND: Topping-off surgery is a newly-developed surgical technique which
      combines rigid fusion with an interspinous process device in the adjacent segment
      to prevent adjacent segment degeneration. There are few reports on Topping-off
      surgery and its rationality and indications remains highly controversial. Our
      study aims to investigate the short-term and mid-term clinical results of Topping
      off surgery in preventing adjacent segment degeneration when mild or moderate
      adjacent segment degeneration existed before surgery. METHODS: The 25 cases that
      underwent L5-S1 posterior lumbar interbody fusion (PLIF) + L4-L5 interspinous
      process surgeries between April 2008 and March 2010 formed Topping-off group. The
      42 cases undergoing L5-S1 PLIF surgery formed PLIF group. Both groups matched in
      gender, age, body mass index and Pfirrmann grading (4 to 6). The patients were
      evaluated with visual analogue scale (VAS) and Japanese orthopaedic association
      (JOA) scores before surgery and in the last follow-up. Modic changes of endplates
      were recorded. RESULTS: The follow-up averaged 24.8 and 23.7 months. No
      symptomatic or radiological adjacent segment degeneration was observed. There was
      no significant difference in intraoperative blood loss or postoperative drainage.
      VAS and lumbar JOA scores improved significantly in both groups (t = 12.1 and
      13.5, P < 0.05). Neither anterior nor posterior disc height was significantly
      changed. Segmental lordosis of L4-L5 and total lordosis were all increased
      significantly (Topping-off group: t = -2.30 and -2.24,P < 0.05; PLIF group: t = 
      2.76 and -1.83, P < 0.01). In the hyperextension and hyperflexion view, Topping
      off group's range of motion (ROM) and olisthesis in the L4-L5 segment did not
      significantly change in flexion, but decreased in extension. In PLIF group, ROM
      (t = -7.82 and -4.90, P < 0.01) and olisthesis (t = -15.67 and -18.58, P < 0.01)
      both significantly increased in extension and flexion. CONCLUSIONS: Compared with
      single segment PLIF surgery, Topping-off surgery can achieve similar symptomatic
      improvement in cases with pre-existing mild or moderate adjacent segment
      degeneration, restrict the adjacent segment's ROM in extension and prevent
      excessive olisthesis of adjacent segment in both extension and flexion.

PMID- 23158122
TI  - Minimally invasive transforaminal lumbar interbody fusion aided with computer
      assisted spinal navigation system combined with electromyography monitoring.
AB  - BACKGROUND: Minimally invasive techniques are gaining wide-spread application in
      lumbar fusion surgery, because they may have advantage over conventional open
      surgery in approach-related morbidity. This research was aimed to evaluate the
      safety and accuracy of the techniques of minimally invasive transforaminal lumbar
      interbody fusion by using a computer-assisted spinal navigation system combined
      with electromyography monitoring. METHODS: Sixteen patients underwent minimally
      invasive transforaminal lumbar interbody fusion. A computer-assisted spinal
      navigation system and electromyography were used for guiding pedicle screw
      placement. The operative duration, blood loss, complications, and fluoroscopic
      time were recorded. Clinical outcome was assessed by Visual Analog Scale and
      Oswestry Disability Index. Radiographic images were obtained to evaluate the
      accuracy of pedicle screw placement and fusion rates. RESULTS: The Visual Analog
      Scale and Oswestry Disability Index scores were vastly improved postoperatively.
      A total of 64 pedicle screws were implanted and three were regarded as
      misplacement by post-operative CT scan. Three screw trajectories were adjusted
      according to intra-operative stimulus-evoked electromyography monitoring. The
      average fluoroscopy time in each patient was 31.8 seconds, which equals to 7.9
      seconds per pedicle screw. No patients had instrument related neurological
      complications, infection, implant failure or revision. Successful fusion was
      found in all patients. CONCLUSIONS: The combination of navigation system and real
      time electromyography monitoring can make the minimally invasive operation more
      safe and accurate while decreasing radiation exposure time of the medical staff
      and patient and minimizing the chance and the degree of the pedicle screw
      misplacement.

PMID- 23158123
TI  - Sex, age, and annual incidence of primary total knee arthroplasty: a university
      affiliated hospital survey of 3118 Chinese patients.
AB  - BACKGROUND: In recent years, the number of patients undergoing primary total knee
      arthroplasty in China has rapidly increased. However, the incidence of primary
      total knee arthroplasty is unknown. The purpose of this study was to investigate
      the sex, age and, annual incidence of primary total knee arthroplasty based on
      3118 Chinese patients who underwent the procedure during the period of 2000 -
      2011. METHODS: Total knee arthroplasties were performed on 511 males and 2607
      females in our hospital during the period of 2000 - 2011. The sex, age, and
      annual incidence of primary total knee arthroplasty were evaluated. RESULTS: The
      annual incidence of primary total knee arthroplasty increased from 35 knees in
      2000 to 681 knees in 2011. The average annual percentage increase in incidence
      was 33.2%. Females accounted for 83.2% of the patients who underwent primary
      total knee arthroplasty. In both males and females, the highest incidence was
      observed in the group aged 65 - 74 years. CONCLUSIONS: This study demonstrated a
      rapid increase in the incidence of primary total knee arthroplasty in our Chinese
      study population. The sex and age incidence of primary total knee arthroplasty in
      our study population differed from those reported in Western populations.

PMID- 23158124
TI  - Lower-limb valgus deformity associated with developmental hip dysplasia.
AB  - BACKGROUND: Treating developmental dysplasia of the hip is often challenging. The
      difficulties include not only the hip surgery itself but also the treatment of
      the associated lower-limb valgus deformity. However, there have been very few
      studies on such deformity in patients with developmental hip dysplasia. In this
      study, we investigated the prevalence and severity of lower-limb valgus
      deformity, along with the relationship between the severity of valgus deformity
      and mechanical alterations of the hip or the ipsilateral knee. METHODS: Two
      hundred and six affected lower limbs of 116 adult patients with untreated
      developmental dysplasia of the hip were included in the study, grouped according
      to the severity of hip dysplasia. Each study participant's radiographs were
      measured to quantitatively evaluate the mechanical axis deviation of the lower
      limb, and further to evaluate the prevalence and severity of the lower-limb
      valgus deformity. Some mechanical alterations of the hip and the ipsilateral knee
      were also measured on the radiographs. RESULTS: Of the affected lower limbs,
      14.1% had valgus deformities. Study participants with Crowe type III hip
      dysplasia had the most severe deformity and the highest prevalence of deformity.
      Severity of valgus deformity had a strong positive correlation with the lateral
      migration of the femoral head but not with the superior migration. A decreased
      lateral distal femoral angle contributed to the lower-limb valgus deformity, and
      the lateral distal femoral angle had a strong negative correlation with the
      severity of valgus deformity. CONCLUSIONS: Hip dysplasia is commonly associated
      with lower-limb valgus deformity, and the severity of the lower-limb valgus
      deformity is mostly affected by lateral migration but not superior migration of
      the femoral head. The valgus deformity may originate mainly in the distal femur,
      in addition to the hip joint itself. These findings can be taken into account
      when planning to treat the patients with hip dysplasia.

PMID- 23158125
TI  - Characteristics of bone tunnel changes after anterior cruciate ligament
      reconstruction using Ligament Advanced Reinforcement System artificial ligament.
AB  - BACKGROUND: There are different materials used for anterior cruciate ligament
      (ACL) reconstruction. It has been reported that both autologous grafts and
      allografts used in ACL reconstruction can cause bone tunnel enlargement. This
      study aimed to observe the characteristics of bone tunnel changes and possible
      causative factors following ACL reconstruction using Ligament Advanced
      Reinforcement System (LARS) artificial ligament. METHODS: Forty-three patients
      underwent ACL reconstruction using LARS artificial ligament and were followed up
      for 3 years. X-ray and CT examinations were performed at 1, 3, 6, 12, 24, and 36
      months after surgery, to measure the width of tibial and femoral tunnels. Knee
      function was evaluated according to the Lysholm scoring system. The anterior and
      posterior stability of the knee was measured using the KT-1000 arthrometer.
      RESULTS: According to the Peyrache grading method, grade 1 femoral bone tunnel
      enlargement was observed in three cases six months after surgery. No grade 2 or
      grade 3 bone tunnel enlargement was found. The bone tunnel enlargement in the
      three cases was close to the articular surface with an average tunnel enlargement
      of (2.5 +/- 0.3) mm. Forty cases were evaluated as grade 0. The average tibial
      and femoral tunnel enlargements at the last follow-up were (0.8 +/- 0.3) and (1.1
      +/- 0.3) mm, respectively. There was no statistically significant difference in
      bone tunnel width changes at different time points (P > 0.05). X-ray and CT
      measurements were consistent. CONCLUSIONS: There was no marked bone tunnel
      enlargement immediately following ACL reconstruction using LARS artificial
      ligament. Such enlargement may, however, result from varying grafting factors
      involving the LARS artificial ligament or from different fixation methods.

PMID- 23158126
TI  - Minimally invasive treatment of the KobyGard system for plantar fasciitis: a
      retrospective study.
AB  - BACKGROUND: Calcodynia is a persistent condition that podiatric surgeons
      frequently see among their patients, and plantar fasciitis is the main reason for
      pain. When systematic conservative treatments fail to alleviate these conditions,
      it requires surgical intervention, mainly plantar fascia release surgery, which
      used to be an open heel release surgery. This study aimed to investigate whether
      minimally invasive treatment of the KobyGard system is more safe and effective
      for plantar fasciitis. METHODS: From May 2009 to May 2012, a total of nine
      patients, three males and six females with plantar fasciitis, were treated in the
      Peking University People's Hospital with minimally invasive instruments, the
      KobyGard system, for the release of plantar fascia. Three patients, experiencing
      bilateral calcaneodynia, underwent bilateral surgery. One patient had bilateral
      calcaneodynia with enthesiopathy of Achilles tendon, and underwent Achilles
      tendon surgery. Preoperative and postoperative Visual Analogue Scale (VAS),
      American Orthopaedic Foot and Ankle Society (AOFAS) ankle and hindfoot scores,
      Roles and Maudsley scores and SF-36 questionnaires were evaluated. RESULTS: The
      nine patients were successfully followed up. The average postoperative follow-up
      time was 13.2 months and it varied from 2.0 months to 21.0 months. Pre- and
      postoperative average scores of VAS was 9.3 and 1.9 (P < 0.001), respectively.
      Pre- and postoperative average scores of AOFAS hind foot was 36.0 and 82.0 (P <
      0.001), respectively. There was also a statistically significant amelioration in
      SF-36 scores and the Roles and Maudlesy scores. Eight patients were satisfied
      with the surgery outcome. CONCLUSION: Minimally invasive surgery treatment of the
      KobyGard system for plantar fasciitis has the advantages of shorter operation
      time, ease of operation, and similar satisfaction rates with open surgery, but
      with smaller surgical incision.

PMID- 23158127
TI  - Anatomical study of the anterolateral and posteromedial bundles of the posterior
      cruciate ligament for double-bundle reconstruction using the quadruple bone
      tunnel technique.
AB  - BACKGROUND: Several techniques have been described for posterior cruciate
      ligament (PCL) reconstruction. However, double-bundle PCL reconstruction using
      the quadruple bone-tunnel technique has been seldom reported. The current study
      investigated this technique, focusing on the anatomy of the femoral and tibial
      insertions of the anterolateral (AL) and posteromedial (PM) bundles of the PCL.
      METHODS: Twenty-two fresh, healthy adult cadaveric knees were dissected and
      measured. The PCL was divided into the AL bundle and PM bundle at the insertion
      footprint. The insertion footprints of the AL and PM bundles, their location,
      size, and the clock positions were measured and described. RESULTS: On the femur,
      the clock position of the footprint of the AL bundle was 11:21 +/- 0:23 (left) or
      0:39 +/- 0:23 (right), and the PM bundle was 9:50 +/- 0:18 (left) or 2:10 +/-
      0:18 (right), with the knee flexed at 90 degrees. The distances from the center
      of the femoral insertions of the AL and PM bundles to the anterior cartilage
      margins of the medial femoral condyle were (7.79 +/- 1.22) mm and (8.36 +/- 1.63)
      mm, respectively. On the tibia, the vertical distances from the center of the
      tibial insertions of the AL and PM bundles to the tibial articular surface were
      (3.25 +/- 1.20) mm and (6.91 +/- 1.57) mm, respectively. CONCLUSIONS: These
      results have led to a better definition of the anatomy of the AL and PM bundle
      footprint of the PCL. The technique of double-bundle PCL reconstruction using
      quadruple bone-tunnel is feasible. Application of these data during PCL
      reconstruction using the quadruple bone-tunnel technique may help optimize knee
      stability.

PMID- 23158128
TI  - Epidural fentanyl decreases the minimum local analgesic concentration of epidural
      lidocaine.
AB  - BACKGROUND: Epidural lidocaine can be used when regional anesthesia needs to be
      established quickly, but the effect of co-administering epidural fentanyl on the
      minimum local analgesic concentration (MLAC) of lidocaine is not known. We
      compared the MLAC of epidural lidocaine in combination with different doses of
      fentanyl for epidural anesthesia in adults. METHODS: One hundred and twenty
      patients requiring epidural analgesia were randomly allocated to receive 20 ml of
      one of four solutions: lidocaine, or lidocaine plus fentanyl 1 ug/ml, 2 ug/ml, or
      3 ug/ml. The first patient in each group was administered 1% lidocaine weight by
      volume; subsequent patients received a concentration determined by the response
      of the previous patient to a higher or lower concentration according to up and
      down sequential allocation in 0.1% increments. Efficacy was assessed using a
      visual analog pain scale, and accepted if this was = 10 mm on a 100 mm scale
      within 30 minutes. The extent of motor block and of nausea and vomiting were
      recorded at 30 minutes after administration of the epidural solution and two
      hours after surgery, respectively. RESULTS: The MLAC of lidocaine in those
      receiving lidocaine alone was 0.785% (95%CI 0.738 - 0.864). A significant dose
      dependent reduction was observed with the addition of fentanyl: the MLAC of
      lidocaine with fentanyl at 2 ug/ml was 0.596% (95%CI 0.537 - 0.660) and 0.387%
      with fentanyl at 3 ug/ml (95%CI 0.329 - 0.446, P < 0.001). CONCLUSION: Epidural
      fentanyl significantly reduces the dose of lidocaine required for effective
      epidural analgesia in adults without causing adverse side effects.

PMID- 23158129
TI  - An Asian population-based survival analysis of patients with distal esophageal
      and gastric cardia adenocarcinomas.
AB  - BACKGROUND: Gastroesophageal junction adenocarcinomas include adenocarcinomas of
      the distal esophagus (DE) and gastric cardia (GC). It is controversial whether
      these tumors are the same entity and whether they have the same survival rates.
      Patients with DE and GC adenocarcinomas have a similar survival rate in the US;
      however, data are lacking in Asian countries. Therefore, we conducted a
      retrospective study to understand the implications of the tumor location in the
      survival of Asian patients. METHODS: A total of 209 patients with pathologically
      confirmed DE and GC adenocarcinomas, from 2005 to 2007, were included in the
      study. We identified patients with adenocarcinomas of the DE (DE group, n = 91)
      and GC (GC group) (n = 118). We performed an unadjusted survival analysis using
      the Kaplan-Meier method, and used a Cox proportional hazards regression model to
      adjust for potential confounding covariates. RESULTS: We found no significant
      difference between the overall survival of the DE and GC groups. The 3-year
      survival rates were 44.8% and 53.0%, respectively, and the 5-year survival rates
      were 27.9% and 30.2%, respectively (P = 0.162). We found no significant
      difference in early staging, advanced staging, different T staging, and different
      N staging, between the groups. Both advanced post-operative N staging and
      advanced AJCC staging had a significant adverse effect on survival. CONCLUSIONS:
      Patients with DE and GC adenocarcinomas have similar survival rates in the Asian
      population. Both post-operative N staging and AJCC staging are prognostic
      factors.

PMID- 23158130
TI  - Follicular fluid levels of prostaglandin E2 and the effect of prostaglandin E2 on
      steroidogenesis in granulosa-lutein cells in women with moderate and severe
      endometriosis undergoing in vitro fertilization and embryo transfer.
AB  - BACKGROUND: The mechanisms of endometriosis with infertility have not been fully
      studied. The present study aimed to assess the follicular fluid (FF) levels of
      prostaglandin E2 (PGE2), which plays a critical role within the ovary, and to
      investigate the effect of PGE2 on steroidogenesis in granulosa-lutein cells
      (GLCs) from women with and without endometriosis. METHODS: Thirty-three women
      with laparoscopically documented endometriosis and 40 controls undergoing in
      vitro fertilization (IVF) were studied. We assayed the concentrations of PGE2 in
      FF, the production of E2 and progesterone in FF and in culture medium, and the
      expression of steroidogenic acute regulatory protein (StAR) and CYP19A1 in GLCs
      with the intervention of PGE2. RESULTS: PGE2 and progesterone concentrations were
      increased and displayed positive correlation in endometriotic FF. PGE2 induced
      the expression of StAR and the production of progesterone in GLCs from women with
      endometriosis, and the expression of StAR and the production of progesterone were
      increased in GLCs from women with endometriosis. However, there were no
      significant effects of PGE2 on promoting the production of E2 or the expression
      of CYP19A1 in GLCs. Moreover, the production of E2 and the expression of CYP19A1
      in GLCs from women with endometriosis were significantly decreased compared to
      the controls. CONCLUSIONS: PGE2 concentrations are increased in endometriotic FF,
      along with concomitant increases in progesterone and StAR. In contrast, the E2
      and CYP19A1 are decreased in GLCs, which may delay the development of the
      follicles and cause an imbalance in the follicular steroid hormone levels. These
      changes may have close relationship with endometriosis-associated infertility.

PMID- 23158131
TI  - Detection of carboxyhemoglobin in patients with hepatic encephalopathy due to
      hepatitis B virus-related cirrhosis.
AB  - BACKGROUND: The heme oxygenase/carbon monoxide (HO/CO) system plays an important
      role in the development of hepatic fibrosis. The level of the HO/CO can be
      directly obtained by determining the carboxyhemoglobin (COHb) level. The aims of
      this study were to reveal the significance of COHb in patients with hepatitis B
      virus-related cirrhosis (HBC) complicated by hepatic encephalopathy (HE), and to
      further investigate the influence of the HO/CO pathway on the end-stage
      cirrhosis, hoping to find a reliable indicator to evaluate the course of HBC.
      METHODS: According to the diagnostic criteria, 63 HBC inpatients with HE were
      enrolled in group H. Patients regaining awareness with current therapies were
      categorized into group P-H. Comparisons were made with a control group (group N)
      consisting of 20 health volunteers. The levels of COHb, partial pressure of
      oxygen (PaO2) and oxygen saturation (SaO2) were determined by arterial blood gas
      analysis method. The incidences of hepatorenal syndrome (HRS), upper
      gastrointestinal bleeding, esophagogastric varices and spontaneous bacterial
      peritonitis (SBP) in group H were recorded. COHb levels in different groups were
      compared, and the correlations of COHb levels with HE grades (I, II, III, and
      IV), PaO2, SaO2 and hypoxemia were analyzed. RESULTS: The COHb level in group P-H
      ((1.672 +/- 0.761)%) was significantly higher than that in group N ((0.983 +/-
      0.231)%) (P < 0.01), and the level in group H ((2.102 +/- 1.021)%) was
      significantly higher than groups P-H and N (P < 0.01). A positive correlation was
      observed between the COHb concentration and the grade of HE (r(s) = 0.357, P =
      0.004). There were no significant differences of COHb levels between HE patients
      with and without complications such as esophagogastric varices ((2.302 +/-
      1.072)% vs. (1.802 +/- 1.041)%, P > 0.05) or the occurrence of SBP ((2.960 +/-
      0.561)% vs. (2.030 +/- 1.021)%, P > 0.05). Compared with HE patients with HRS,
      the level of COHb was significantly higher in HE patients without HRS ((2.502 +/-
      1.073)% vs. (1.981 +/- 1.020)%, P = 0.029). The COHb level had a negative
      correlation with PaO2 (r = -0.335, P = 0.007) while no statistically significant
      relationship was found with SaO2 (r = -0.071, P > 0.05). However, when the above
      two parameters met the diagnostic criteria of hypoxemia, the COHb concentration
      increased ((2.621 +/- 0.880)% vs. (1.910 +/- 0.931)%, P = 0.011). CONCLUSIONS:
      COHb is a potential candidate to estimate the severity and therapeutic effect of
      HE. The levels of COHb may be tissue-specific in cirrhotic patients with
      different complications.

PMID- 23158132
TI  - Association of interleukin-6 and C-reactive protein genetic polymorphisms levels
      with venous thromboembolism.
AB  - BACKGROUND: Increased levels of interleukin-6 (IL-6) and C-reactive protein (CRP)
      have been reported in patients with venous thromboembolisms (VTE). However,
      prospective studies did not confirm an association between IL-6, CRP and their
      polymorphism with the risk of VTE. METHODS: One hundred and forty patients
      (including 66 males and 74 females, mean age (55.55 +/- 17.11) years) and one
      hundred and sixty controls (including 74 males and 86 females, mean age (56.58 +/
      12.24) years) were involved. An enzyme linked immunosorbent assay (ELISA) method
      was used for detecting the serum levels of inflammatory factors IL-6 and CRP in
      both groups. Polymerase chain reaction-restriction fragment length polymorphism
      (PCR-RFLP) was used for analyzing the distribution of polymorphisms at the 
      572C/G and -597G/A sites of the promoter of the IL-6 gene and at 1059G/C of the
      CRP gene. RESULTS: Serum levels of IL-6 and CRP were significantly higher in the
      VTE group than in the control group (P < 0.05). The frequencies of -572C/G
      promoter polymorphisms CC, CG, and GG in the IL-6 gene were found to be 34%, 48%,
      and 18%, respectively, and the derived allele frequencies for the C and G alleles
      were 58% and 42%. There was a significant difference in the -572C/G promoter
      polymorphisms between the VTE group and control group (P < 0.05). For the -597G/A
      polymorphism, individuals all carried the GG and GA type; AA genotypes were not
      detected. The frequency of the GG, GC, and CC genotypes at the CRP1059G/C
      promoter was 87.57%, 7.86% and 3.57% in VTE group, while 86.25%, 10%, and 3.75%
      in control group, respectively. The frequency of G and C alleles at CRP 1059G/C
      was 91.43% and 8.57% in VTE group and 91.56% and 8.44% in the control group. The
      results showed that there was no statistically significant difference of 1059G/C
      genotype and mutation frequency of the allele between the VTE group and control
      group (P > 0.05). Multiple Logistic regression analysis showed CC homozygotes of
      the IL-6 -572G/C, body mass index (BMI), and CRP, IL-6, and high-density
      lipoprotein cholesterol (HDL-C) were independent risk factors for VTE (P < 0.05).
      CONCLUSIONS: We found that VTE was associated with IL-6 and CRP levels, and there
      was an association of IL-6 and its promoter polymorphism at -572G/C with the risk
      of VTE. Thus far, a causal relationship between inflammation and VTE remains to
      be clarified and more prospective data are required.

PMID- 23158133
TI  - Expression of Yes-associated protein in non-small cell lung cancer and its
      relationship with clinical pathological factors.
AB  - BACKGROUND: Yes-associated protein (YAP) plays an important role in signal
      transduction and gene transcription regulation in normal cells, with elevated and
      over-expressed YAP levels observed in various malignant tumors. The aim of this
      study was to investigate the expression of YAP in non-small cell lung cancer
      (NSCLC), and to study the possible relationship of YAP expression with the
      occurrence and development of NSCLC. METHODS: YAP expression was assessed in 40
      cases of NSCLC tumor tissues by immunohistochemistry, and their protein and mRNA
      levels were evaluated through Western blotting and reverse transcription
      polymerase chain reaction (PCR), respectively. Normal lung tissues obtained from
      the same patient were used as control. Statistical analysis was performed to
      correlate the YAP expression to clinical pathological factors, such as tumor
      type, stage and grade. RESULTS: YAP-positive expression was found in 28 (70%) of
      the 40 cases of NSCLC, which included 10 cases of squamous cell carcinoma (25%),
      17 cases of adenocarcinoma (42.5%) and 1 case of squamous adenocarcinoma (2.5%).
      In the 28 YAP-positive cases, 19 cases showed lymph node metastasis and were
      classified in TNM stage II + III (47.5%); the other nine cases showed no lymph
      node metastasis (22.5%) and were classified in the TNM stage I. There was no
      relationship between YAP expression and patients' age, gender or tumor
      histological grades. However, YAP showed significant over expression in late
      period of T stage (P = 0.012), TNM stage (P = 0.039), and lymph node metastasis
      (P = 0.013), respectively. Notably, YAP-positive expression was significantly
      higher in adenocarcinoma than that in squamous cell carcinoma (P = 0.041).
      CONCLUSIONS: Over-expression of YAP was associated with NSCLC, especially lung
      adenocarcinoma. The high YAP expression in late period of tumor stage and lymph
      node metastasis may indicate that YAP expression could be an early marker for
      NSCLC tumorigenesis.

PMID- 23158134
TI  - Effect of combining different calcium concentration dialysate on calcium balance
      in peritoneal dialysis patients.
AB  - BACKGROUND: Calcium and phosphorus metabolic disturbance are common in dialysis
      patients and associated with increased morbidity and mortality. Therefore,
      maintaining the balance of calcium and phosphate metabolism and suitable intact
      parathyroid hormone (iPTH) level has become the focus of attention. We
      investigated the effects of different peritoneal dialysate calcium concentrations
      on calcium phosphate metabolism and iPTH in continuous ambulatory peritoneal
      dialysis (CAPD) patients. METHODS: Forty stable CAPD patients with normal serum
      calcium were followed for six months of treatment with 1.25 mmol/L calcium
      dialysate (DCa1.25, PD4, 22 patients) or a combination of 1.75 mmol/L calcium
      dialysate (DCa1.75, PD2) and PD4 (18 patients) twice a day respectively. Total
      serum calcium (after albumin correction), serum phosphorus, iPTH, alkaline
      phosphatase (ALP) and blood pressure were recorded before and 1, 3 and 6 months
      after treatment commenced. RESULTS: No significant difference was found in
      baseline serum calcium, phosphorus between the two patient groups, but the levels
      of iPTH were significantly different. No significant changes were found in the
      dosage of calcium carbonate and active vitamin D during 6 months. In the PD4
      group, serum calcium level at the 1st, 3rd, 6th months were significantly lower
      than the baseline (P < 0.05). There was no significant difference in serum
      phosphorus after 6 months treatment. iPTH was significantly higher (P < 0.001) at
      the 1st, 3rd, and 6th months compared with the baseline. No differences were seen
      in ALP and blood pressure. In the PD4+PD2 group, no significant changes in serum
      calcium, phosphorus, iPTH, ALP and BP during the 6-month follow-up period.
      CONCLUSIONS: Treatment with 1.25 mmol/L calcium dialysate for six months can
      decrease serum calcium, increase iPTH, without change in serum phosphorus, ALP,
      and BP. The combining of PD4 and PD2 can stabilize the serum calcium and avoid
      fluctuations in iPTH levels.

PMID- 23158135
TI  - Cryoglobulinemia is an independent factor negatively associated with sustained
      virological response in chronic hepatitis C patients.
AB  - BACKGROUND: Mixed cryoglobulinemia (MC) is one of the most common and severe
      symptoms in chronic hepatitis C patients. The aim of this study was to
      investigate whether mixed cryoglobulinemia is a factor associated with sustained
      virological response in chronic hepatitis C patients treated with combination
      therapy of pegylated interferon alpha-2a and ribavirin. METHODS: This is a single
      center study including 57 chronic hepatitis C patients who received combination
      treatments of pegylated interferon alfa-2a and ribavirin. Serum cryoglobulin was
      detected by cryoprecipitation prior to treatment. Serum hepatitis C virus (HCV)
      RNA levels were checked before treatment, during the fourth and 12th week of
      treatment, and during the 24th week after cessation of treatment. The genotype of
      HCV was determined at baseline. Logistic regression analysis was used to assess
      the factors associated with sustained virological response. RESULTS: Twenty-five
      patients were with MC (43.9%). Twenty-four weeks after cessation of antiviral
      treatment, sustained virological response achievement in MC(+) patients was
      significantly lower than that in MC(-) patients (32.0% vs. 75.0%, P = 0.001).
      Univariate Logistic regression analysis and multivariate Logistic regression
      analysis found that only MC (odds ratio: 6.375; 95% CI: 1.998- 20.343, P = 0.002)
      was negatively associated with sustained virological response achievement.
      CONCLUSION: MC is an independent factor negatively associated with sustained
      virological response in chronic hepatitis C patients treated with pegylated
      interferon alpha-2a and ribavirin.

PMID- 23158136
TI  - Clinical evaluation of remineralization potential of casein phosphopeptide
      amorphous calcium phosphate nanocomplexes for enamel decalcification in
      orthodontics.
AB  - BACKGROUND: Enamel decalcification in orthodontics is a concern for dentists and
      methods to remineralize these lesions are the focus of intense research. The aim
      of this study was to evaluate the remineralizing effect of casein phosphopeptide
      amorphous calcium phosphate (CPP-ACP) nanocomplexes on enamel decalcification in
      orthodontics. METHODS: Twenty orthodontic patients with decalcified enamel
      lesions during fixed orthodontic therapy were recruited to this study as test
      group and twenty orthodontic patients with the similar condition as control
      group. GC Tooth Mousse, the main component of which is CPP-ACP, was used by each
      patient of test group every night after tooth-brushing for six months. For
      control group, each patient was asked to brush teeth with toothpaste containing
      1100 parts per million (ppm) of fluoride twice a day. Standardized intraoral
      images were taken for all patients and the extent of enamel decalcification was
      evaluated before and after treatment over this study period. Measurements were
      statistically compared by t test. RESULTS: After using CPP-ACP for six months,
      the enamel decalcification index (EDI) of all patients had decreased; the mean
      EDI before using CPP-ACP was 0.191 +/- 0.025 and that after using CPP-ACP was
      0.183 +/- 0.023, the difference was significant (t = 5.169, P < 0.01). For
      control group, the mean EDI before treatment was 0.188 +/- 0.037 and that after
      treatment was 0.187 +/- 0.046, the difference was not significant (t = 1.711, P >
      0.05). CONCLUSION: CPP-ACP can effectively improve the demineralized enamel
      lesions during orthodontic treatment, so it has some remineralization potential
      for enamel decalcification in orthodontics.

PMID- 23158137
TI  - Tumorigenesis and spontaneous metastasis by luciferase-labeled human xenograft
      osteosarcoma cells in nude mice.
AB  - BACKGROUND: Osteosarcoma (OS) is the most common primary malignant tumor of bone.
      Mouse models of human OS can invariably provide greater insight into the complex
      mechanisms that underlie the development and pathogenesis of this aggressive
      tumor. Bioluminescence technology favored tracing cancer cells in vivo. In this
      study, an OS model was described and evaluated using human OS cell line, Saos2,
      labeled with luciferase (Saos2-luc). METHODS: Saos2 cells were infected by
      lentivirus loading a firefly luciferase gene. Luciferase expression of Saos2-luc
      cells was characterized both in vitro and in vivo. Specific biologic and
      oncologic features of Saos2-luc cells were analyzed. The OS was established as
      orthotopic xenografts in nude mice. Both orthotopic tumors and spontaneous lung
      metastasis were analyzed. RESULTS: Tumorigenesis and spontaneous lung metastasis
      in nude mice could be monitored in vivo through in vivo imaging system. The
      enhancement in proliferation, migration and invasion abilities and the
      attenuation in adhesion ability were observed in Saos2-luc cells compared with
      Saos2 cells. Furthermore, there were the up-regulation of Osteocalcin, CCR10,
      CXCR1 and ID1 and the down-regulation of ALP, collagen I, CCR1, CCR3, CXCR3, NID
      and N-cadherin in Saos2-luc cells compare to Saos2 cells. The rate of spontaneous
      lung metastasis in Saos2-luc cells was higher than that in Saos2 cells, although
      without significant difference. CONCLUSIONS: Lentivirus transfection may cause
      alteration of gene expression profiles and further biological functions. This
      model can be used in the elucidation of molecular mechanisms of tumorigenesis and
      the screening of new therapeutic agents.

PMID- 23158138
TI  - Reconstruction of segmental bone defects in the rabbit ulna using periosteum
      encapsulated mesenchymal stem cells-loaded poly (lactic-co-glycolic acid)
      scaffolds.
AB  - BACKGROUND: Repair of large bone defects remains a challenge for clinicians. The
      present study investigated the ability of mesenchymal stem cells (MSCs) and/or
      periosteum-loaded poly (lactic-co-glycolic acid) (PLGA) to promote new bone
      formation within rabbit ulnar segmental bone defects. METHODS: Rabbit bone marrow
      derived MSCs (passage 3) were seeded onto porous PLGA scaffolds. Forty segmental
      bone defects, each 15 mm in length, were created in the rabbit ulna, from which
      periosteum was obtained. Bone defects were treated with either PLGA alone (group
      A), PLGA + MSCs (group B), periosteum-wrapped PLGA (group C) or periosteum
      wrapped PLGA/MSCs (group D). At 6 and 12 weeks post-surgery, samples were
      detected by gross observation, radiological examination (X-ray and micro-CT) and
      histological analyses. RESULTS: Group D, comprising both periosteum and MSCs,
      showed better bone quality, higher X-ray scores and a greater amount of bone
      volume compared with the other three groups at each time point (P < 0.05). No
      significant differences in radiological scores and amount of bone volume were
      found between groups B and C (P > 0.05), both of which were significantly higher
      than group A (P < 0.05). CONCLUSIONS: Implanted MSCs combined with periosteum
      have a synergistic effect on segmental bone regeneration and that periosteum
      plays a critical role in the process. Fabrication of angiogenic and osteogenic
      cellular constructs or tissue-engineered periosteum will have broad applications
      in bone tissue engineering.

PMID- 23158139
TI  - Association of sterol regulatory element binding protein 2 and insulin-like
      growth factor binding protein 3 genetic polymorphisms with avascular necrosis of
      the femoral head in the Chinese population.
AB  - BACKGROUND: Sterol regulatory element binding protein (SREBP)-2 plays a key role
      in lipid homeostasis by stimulating gene expression of cholesterol biosynthetic
      pathways. The insulin-like growth factor binding protein (IGFBP) family regulates
      growth and metabolism, especially bone cell metabolism, and correlates with
      osteonecrosis. However, association of their gene polymorphisms with risk of
      avascular necrosis of the femoral head (ANFH) has rarely been reported. We
      determined whether SREBP-2 and IGFBP-3 gene polymorphisms were associated with
      increased ANFH risk in the Chinese population. METHODS: Two single nucleotide
      polymorphisms of SREBP2 gene, rs2267439 and rs2267443, and one of IGFBP-3 gene,
      rs2453839, were selected and genotyped in 49 ANFH patients and 42 control
      individuals by direct sequencing assay. RESULTS: The frequencies of rs2267439 TT
      and rs2267443 GA of SREBP2 and rs2453839 TT and CT of IGFBP-3 in the ANFH group
      showed increased and decreased tendencies (against normal control group),
      respectively. Interaction analysis of genes revealed that the frequency of
      carrying rs2267439 TT and rs2267443 GA genotypes of SREBF-2 in ANFH patients was
      significantly higher than in the control group (P < 0.05). Association analysis
      between polymorphisms and clinical phenotype demonstrated that the disease course
      in ANFH patients with the rs2453839 TT genotype of IGFBP-3 was significantly
      shorter than that of CT + CC carriers (P < 0.01). CT + CC genotype frequency in
      patients with stage III/IV bilateral hip lesions was significantly higher than in
      those with stage III/IV unilateral lesions and stage II/III bilateral lesions (P
      < 0.05 - 0.02). CONCLUSIONS: Our results suggested that interaction of SREBP-2
      gene polymorphisms and the relationship between the polymorphisms and clinical
      phenotype of IGFBP-3 were closely related to increased ANFH risk in the Chinese
      population. The most significant finding was that the CT + CC genotype carriers
      of IGFBP-3 rs2453839 were highly associated with the development of ANFH.

PMID- 23158140
TI  - Inhibition of Nogo expression to promote repair after spinal cord injury.
AB  - BACKGROUND: One of the reasons for poor neuroregeneration after central nervous
      system injury is the presence of inhibitory factors such as Nogo. Here, we tested
      the inhibition of Nogo by RNA interference both in vitro and in vivo, using
      recombinant adenovirus-mediated transfection of short hairpin RNAs, to explore a
      new method of treatment for spinal cord injury. METHODS: We designed and cloned
      two Nogo-specific short hairpin RNAs and an unrelated short hairpin RNA, packaged
      the clones into adenovirus, and amplified the recombinant virus in 293 cells. We
      then tested the inhibition of Nogo expression both in vitro in adenovirus
      transfected oligodendrocytes and in vivo in spinal cord tissue from adenovirus
      transfected spinal cord injury model rats. We tested Nogo expression at the mRNA
      level by reverse-transcription PCR and at the protein level by Western blotting
      and immunohistochemistry. RESULTS: In vitro, the two specific Nogo short hairpin
      RNAs decreased Nogo mRNA expression by 51% and 49%, respectively, compared with
      Nogo expression in cells transfected with the unrelated control small hairpin RNA
      (P < 0.005). Similarly, Nogo protein expression decreased by 50% and 48%,
      respectively (P < 0.005). In vivo, in spinal cord injury model rats, the two
      specific Nogo short hairpin RNAs decreased Nogo mRNA expression by 45% and 40%,
      respectively, compared with Nogo expression in spinal cord injury model rats
      transfected with the unrelated control short hairpin RNA (P < 0.005). The Nogo
      protein level was similarly decreased. CONCLUSIONS: We were successful in
      specifically downregulating Nogo at the mRNA and protein levels by adenovirus
      mediated delivery of short hairpin RNAs, both in vitro and in vivo. This confirms
      the effectiveness of RNA interference for the inhibition of Nogo gene expression
      and the efficiency of using adenovirus for delivery. Thus gene therapy may be an
      effective treatment for spinal cord injury.

PMID- 23158141
TI  - Differentiation of human bone marrow precursor cells into neuronal-like cells
      after transplantation into canine spinal cord organotypic slice cultures.
AB  - BACKGROUND: Treatments to regenerate different tissue involving the
      transplantation of bone marrow derived mesenchymal precursor cells are
      anticipated. Using an alternative methods, in vitro organotypic slice culture
      method, would be useful to transplant cells and assessing the effects. This study
      was to determine the possibility of differentiating human bone marrow precursor
      cells into cells of the neuronal lineage by transplanting into canine spinal cord
      organotypic slice cultures. METHODS: Bone marrow aspirates were obtained from
      posterior superior iliac spine (PSIS) of patients that had undergone spinal
      fusion due to a degenerative spinal disorder. For cell imaging, mesenchymal
      precursor cells (MPCs) were pre-stained with PKH-26 just before transplantation
      to canine spinal cord slices. Canine spinal cord tissues were obtained from three
      adult beagle dogs. Spinal cords were cut into transverse slices of 1 mm using
      tissue chopper. Two slices were transferred into 6-well plate containing 3 ml
      DMEM with antibiotics. Prepared MPCs (1*10(4)) were transplanted into spinal cord
      slices. On days 0, 3, 7, 14, MPCs were observed for morphological changes and
      expression of neuronal markers through immunofluorescence and reverse
      transcription-polymerase chain reaction (RT-PCR). RESULTS: The morphological
      study showed: spherical cells in the control and experiment groups on day 0; and
      on day 3, cells in the control group had one or two thick, short processes and
      ones in the experiment group had three or four thin, long processes. On day 7,
      these variously-sized processes contacted each other in the experiment group, but
      showed typical spindle-shaped cells in the control group. Immunofluorescence
      showed that PKH-26(+) MPCs stained positive for NeuN(+) and GFAP(+) in
      experimental group only. Also RT-PCR showed weak expression of beta-tubulin III
      and GFAP. CONCLUSIONS: Human bone marrow mesenchymal precursor cells (hMPCs) have
      the potential to differentiate into the neuronal like cells in this canine spinal
      cord organotypic slice culture model. Furthermore, these findings suggested the
      possibility that these cells can be utilized to treat patients with spinal cord
      injuries.

PMID- 23158142
TI  - Effect of pcDNA3.1- vascular endothelial growth factor 165 recombined vector on
      vascular buds in rabbit vertebral cartilage endplate.
AB  - BACKGROUND: This study aimed to investigate the effect of pcDNA3.1-vascular
      endothelial growth factor (VEGF)165 vector on vertebral cartilage endplate
      vascular buds and intervertebral discs. METHODS: Rabbits were randomly assigned
      to the control and experimental groups with 10 in each. In the experimental
      group, we anesthetized the rabbits and exposed the front vertebral body. Using
      the mark of the longitudinal ossature of the front vertebral body of the lumbar
      vertebrae, we advanced a needle at the central point of the front fourth and
      fifth lumbar intervertebral discs and injected 20 ul pcDNA3.1-VEGF165. Similarly,
      in the control group, we injected 20 ul pcDNA3.1. At 4 and 8 weeks post
      injection, we examined the changes of the vertebral cartilage endplate using X
      ray radiograph, histology, and scanning electron microscopy. RESULTS: The
      vertebral cartilage endplate calcification and degeneration in the experimental
      group were less than those in the control group at 8 weeks post-operation. The
      average number and diameter of vascular buds obviously increased in the
      experimental group at 4 and 8 weeks post-operation. The number of vascular buds
      and the diameter in the region of the inner annulus increased when compared to
      those in the area near the nucleus pulposus. CONCLUSIONS: The pcDNA3.1-VEGF165
      plasmid can increase the average number and diameter of vascular buds and
      decelerate intervertebral disc degeneration.

PMID- 23158143
TI  - Biomechanical supporting effect of tantalum rods for the femoral head with
      various sized lesions: a finite-element analysis.
AB  - BACKGROUND: Features of necrotic lesions and various interventions could affect
      the biomechanics of the femoral head. A three-dimensional finite-element analysis
      was designed to demonstrate necrotic femoral head stress changes with various
      sizes of necrotic lesions, and evaluate the effect of tantalum rods on preventing
      femoral head cracking. METHODS: Femoral computed tomography scans were used to
      build a normal three-dimensional finite-element femoral head model in a computer.
      Based on the normal model, necrotic models of different lesion diameters (15 mm,
      20 mm and 30 mm) were created, as were the repaired models with tantalum rods for
      each diameter. After a series of meshing and force loading, the von Mises stress
      distributions, simulating single-legged stance, and stresses on specific points
      under loaded conditions were determined for each model. RESULTS: Deep exploration
      into the burdened area of the femoral head indicated that higher stresses to the
      femoral head were observed with a larger necrotic lesion; the largest stress
      concentration, 91.3 MPa, was found on the femoral head with a lesion diameter of
      30 mm. By contrast, topical stress on the surface of the necrotic regions was
      lowered following implantation of a tantalum rod, and the changes in stress were
      significant in models with lesions of 15 mm and 30 mm in diameter, with the best
      biomechanical benefit from the tantalum rod found with a lesion diameter of 15
      mm. CONCLUSIONS: Femoral heads with larger necrotic lesions usually have a higher
      stress concentration and a higher risk of collapse. Various sized lesions on the
      femoral head can benefit from the mechanical support offered by the implantation
      of a tantalum rod; however, femoral heads with smaller sized lesions may benefit
      more. A thorough evaluation of the lesion size should be conducted prior to the
      use of tantalum rod implants in the treatment of femoral head necrosis.

PMID- 23158144
TI  - Patient-specific modeling of facial soft tissue based on radial basis functions
      transformations of a standard three-dimensional finite element model.
AB  - BACKGROUND: An important purpose of orthodontic treatment is to gain the harmonic
      soft tissue profile. This article describes a novel way to build patient-specific
      models of facial soft tissues by transforming a standard finite element (FE)
      model into one that has two stages: a first transformation and a second
      transformation, so as to evaluate the facial soft tissue changes after
      orthodontic treatment for individual patients. METHODS: The radial basis
      functions (RBFs) interpolation method was used to transform the standard FE model
      into a patient-specific one based on landmark points. A combined strategy for
      selecting landmark points was developed in this study: manually for the first
      transformation and automatically for the second transformation. Four typical
      patients were chosen to validate the effectiveness of this transformation method.
      RESULTS: The results showed good similarity between the transformed FE models and
      the computed tomography (CT) models. The absolute values of average deviations
      were in the range of 0.375 - 0.700 mm at the lip-mouth region after the first
      transformation, and they decreased to a range of 0.116 - 0.286 mm after the
      second transformation. CONCLUSIONS: The modeling results show that the second
      transformation resulted in enhanced accuracy compared to the first
      transformation. Because of these results, a third transformation is usually not
      necessary.

PMID- 23158145
TI  - Effect of deep brain stimulation on substantia nigra neurons in a rat model of
      Parkinson's disease.
AB  - BACKGROUND: Parkinson's disease (PD) is a common neurodegenerative disease, which
      occurs mainly in the elderly. Recent studies have demonstrated that apoptosis
      plays an important role in the occurrence and development of PD. Subthalamic
      nucleus deep brain stimulation (STN-DBS) has been recognized as an effective
      treatment for PD. Recent clinical observations have shown that STN-DBS was able
      to delay early PD progression, and experiments in animal models have also
      demonstrated a protective effect of STN-DBS on neurons. However, the correlation
      between the neuron-protective effect of STN-DBS and the progression of substantia
      nigra pars compacta (SNc) neuronal apoptosis is still unknown. The aim of this
      study was to investigate the protective effect and potential mechanism of STN-DBS
      on SNc neurons in PD rats. METHODS: After the establishment of a PD rat model by
      unilateral/2-point injection of 6-hydroxydopamine in the medial forebrain bundle
      of the brain, DBS by implanting electrodes in the STN was administered.
      Behavioral changes were observed, and morphological changes of SNc neurons were
      analyzed by Nissl staining and DNA in situ end-labeling. Through extracellular
      recording of single neuron discharges and microelectrophoresis, the causes of and
      changes in SNc excitability during STN-DBS were analyzed, and the protective
      effect and potential mechanism of action of STN-DBS on SNc neurons in PD rats was
      investigated. RESULTS: SNc neuron apoptosis was significantly decreased (P <
      0.05) in the stimulation group, compared with the sham stimulation PD group.
      Spontaneous discharges of SNc neurons were observed in normal rats and PD model
      rats, and the mean frequency of spontaneous discharges of SNc neurons in normal
      rats ((40.65 +/- 11.08) Hz) was higher than that of residual SNc neurons in PD
      rats ((36.71 +/- 9.23) Hz). Electrical stimulation of the STN in rats was
      associated with elevated excitation in unilateral SNc neurons. However,
      administering the gamma-aminobutyric acid receptor blocker, bicuculline
      significantly reduced SNc neuron excitation, but the change in SNc neuron
      excitation was not present when MK801, a glutamate receptor blocker, was
      administered. CONCLUSIONS: High-frequency stimulation of the STN has a protective
      effect on SNc neurons in PD rats. The possible molecular mechanism may be related
      to changes in the distribution and metabolism of neurotransmitters in the SNc
      region.

PMID- 23158146
TI  - Rapamycin and 3-methyladenine regulate apoptosis and autophagy in bone-derived
      endothelial progenitor cells.
AB  - BACKGROUND: Mammalian target of rapamycin (mTOR) is involved in a caspase
      independent form of programmed cell death called autophagy. The aim of this
      research was to investigate the effects of rapamycin and 3-methyladenine (3-MA)
      on autophagy, proliferation, apoptosis, and cell-cycle parameters of rat bone
      marrow-derived endothelial progenitor cells (EPCs). METHODS: Mononuclear cells
      isolated from rat bone marrow were treated with rapamycin (0.01, 0.1, 1, or 10
      ug/L) or 3-MA (1.25, 2.5, 5, or 10 mmol/L) for 24 hours. Expression of the
      autophagy marker protein LC3-II was analyzed by Western blotting. Apoptosis and
      cell-cycle progression were analyzed by flow cytometry. Cell proliferation was
      measured using the MTT assay. RESULTS: Rapamycin treatment of EPCs induced
      apoptosis and autophagy and inhibited proliferation and cell-cycle progression in
      a dose-dependent manner. Treatment with 5 mmol/L 3-MA promoted cell
      proliferation; in contrast, treatment with 10 mmol/L 3-MA promoted apoptosis and
      induced S-phase arrest. CONCLUSIONS: Rapamycin treatment of EPCs induced
      apoptosis and autophagy. Low concentrations of 3-MA had no significant effect on
      the proliferation and apoptosis of EPCs; The 5 mmol/L group promoted cell
      proliferation, but had no effect on the apoptosis; the 10 mmol/L group inhibited
      the proliferation and promoted apoptosis through the cell cycle.

PMID- 23158147
TI  - Investigation of long-term implantation of BuMA stent in a porcine coronary
      model.
AB  - BACKGROUND: Stent-based delivery of sirolimus has been shown to reduce neointimal
      hyperplasia significantly. However, the long-term effect of the polymer is
      thought to initiate and sustain an inflammatory response and contribute to the
      occurrence of late complications. Our study aimed to evaluate the efficacy and
      safety of the BuMA biodegradable drug-coated sirolimus-eluting stent (BSES) for
      inhibiting neointimal hyperplasia in a porcine coronary model. METHODS: Four
      types of stents were implanted at random in different coronary arteries of the
      same pig: BSES (n = 24), bare metal stent (BMS) (n = 24), biodegradable polymer
      coated stent without drug (PCS) (n = 24) and only poly (n-butyl methacrylate)
      base layer coated stent (EGS) (n = 23). In total, 26 animals underwent successful
      random placement of 95 oversized stents in the coronary arteries. Coronary
      angiography was performed after 28 days, 90 days and 240 days of stent
      implantation. After 14 days, 28 days, 90 days and 240 days, 6 animals at each
      timepoint were sacrificed for histomorphologic analysis. RESULTS: The 28-day, 90
      day and 240-day results of quantitative coronary angiography (QCA) showed
      reduction in luminal loss (LL) in the BSES group when compared with the BMS
      group; (0.20 +/- 0.35) mm vs. (0.82 +/- 0.51) mm (P = 0.035), (0.20 +/- 0.30) mm
      vs. (0.93 +/- 0.51) mm (P = 0.013), and (0.18 +/- 0.16) mm vs. (0.19 +/- 0.24) mm
      (P = 0.889), respectively. By 28-day, 90-day and 240-day histomorphomeric
      analysis results, there was also a corresponding significant reduction in
      neointimal tissue proliferation with similar injury scores of BSES compared with
      the BMS control; average neointimal area (0.90 +/- 0.49) mm(2) vs. (2.16 +/-
      1.29) mm(2) (P = 0.049), (1.53 +/- 0.84) mm(2) vs. (3.41 +/- 1.55) mm(2) (P =
      0.026), and (2.43 +/- 0.95) mm(2) vs. (3.12 +/- 1.16) mm(2) (P = 0.228),
      respectively. High magnification histomorphologic examination revealed similar
      inflammation scores and endothelialization scores in both the BSES and BMS
      groups. CONCLUSIONS: The BuMA biodegradable drug-coated sirolimus-eluting stents
      can significantly reduce neointimal hyperplasia and in-stent restenosis. Re
      endothelialization of the BuMA stent is as good as that of the BMS in the porcine
      coronary model due to the reduced inflammation response to the BuMA stent.

PMID- 23158148
TI  - Effect of kappa elastin on melanogenesis in A375 human melanoma cells and its
      related mechanism.
AB  - BACKGROUND: Elastin derived peptides can regulate melanocyte precursor
      development. Ultraviolet irradiation, infrared radiation and heat can increase
      the synthesis of tropoelastin in human skin epidermis. The aim of this study was
      to investigate whether the over expressed tropoelastin in epidermis has some role
      in melanogenesis of melanocytes. METHODS: A375 human melanoma cells were treated
      with different concentrations of kappa elastin for 24 hours. A375 human melanoma
      cells were randomly assigned to control, kappa elastin, and lactose pre-incubated
      groups. The cell viabilities were detected by the methyl thiazoleterazolium
      assay. Melanin content and tyrosinase activity in A375 melanoma cells were
      measured. The expressions of endothelin B receptor (ET(B)R) mRNA and c-kit mRNA
      in A375 melanoma cells were measured by quantative reverse transcription
      polymerase chain reaction. RESULTS: Fifty ug/ml of kappa elastin significantly
      increased the melanin content by 56.64% compared with the control (P < 0.05).
      Kappa elastin increased cellular tyrosinase activity by 46.73% compared with the
      control at 24 hours (P < 0.05). Kappa elastin increased the expressions of ET(B)R
      and c-kit mRNA levels by 2.13-fold and 2.47-fold compared with the controls,
      respectively. When pre-incubating cells with a lactose solution (10 mmol/L), the
      inhibition on melanin production was 34.96% compared with the kappa elastin group
      (P < 0.05), tyrosinase activity was inhibited by 29.93% compared with kappa
      elastin group (P < 0.05), and the expressions of ET(B)R mRNA and c-kit mRNA were
      decreased by 1.56-fold and 0.82-fold compared with kappa elastin group,
      respectively. CONCLUSION: Kappa elastin increased the melanogenesis in A375
      melanoma cells via the stimulation of tyrosinase activity and the expression of
      ET(B)R and c-kit. The over expressed tropoelastin produced by keratinocytes might
      play a role in melanogenesis of epidermal melanocytes.

PMID- 23158149
TI  - Mechanical loading induced expression of bone morphogenetic protein-2, alkaline
      phosphatase activity, and collagen synthesis in osteoblastic MC3T3-E1 cells.
AB  - BACKGROUND: Bone morphogenetic protein (BMP)-2, alkaline phosphatase (ALP), and
      collagen type I are known to play a critical role in the process of bone
      remodeling. However, the relationship between mechanical strain and the
      expression of BMP-2, ALP, and COL-I in osteoblasts was still unknown. The purpose
      of this study was to investigate the effects of different magnitudes of
      mechanical strain on osteoblast morphology and on the expression of BMP-2, ALP,
      and COL-I. METHODS: Osteoblast-like cells were flexed at four deformation rates
      (0, 6%, 12%, and 18% elongation). The expression of BMP-2 mRNA, ALP, and COL-I in
      osteoblast-like cells were determined by real-time quantitative reverse
      transcription polymerase chain reaction, respectively. The results were subjected
      to analysis of variance (ANOVA) using SPSS 13.0 statistical software. RESULTS:
      The cells changed to fusiform and grew in the direction of the applied strain
      after the mechanical strain was loaded. Expression level of the BMP-2, ALP, and
      COL-I increased magnitude-dependently with mechanical loading in the experimental
      groups, and the 12% elongation group had the highest expression (P < 0.05).
      CONCLUSION: Mechanical strain can induce morphological change and a magnitude
      dependent increase in the expression of BMP-2, ALP, and COL-I mRNA in osteoblast
      like cells, which might influence bone remodeling in orthodontic treatment.

PMID- 23158150
TI  - Effects of estrogen on collagen gel contraction by human retinal glial cells.
AB  - BACKGROUND: There are definite gender differences in patients with macular holes.
      Menopausal women over 50 years are most affected. We aimed to observe the effect
      of estrogen on collagen gel contraction by cultured human retinal glial cells. It
      is speculated that estrogen could strengthen the tensile stress of the macula by
      maintaining the correct morphology and contraction. METHODS: Estrogen was used to
      determine its effects on collagen gel contraction, and its function was measured
      using morphological changes in cells. Human retinal glial cells were cultured in
      collagen solution. The cells were then exposed to collagen gels and the degree of
      contraction of the gel was determined. RESULTS: Estrogen at differing
      concentrations had no effect on the growth of human retinal glial cells. However,
      after exposed to collagen gel block, less contraction was noted in the estrogen
      treated group than in the control group. CONCLUSIONS: Estrogen can inhibit
      collagen gel contraction by glial cells. These results suggest a mechanism for
      macular hole formation, which is observed in menopausal females.

PMID- 23158151
TI  - Relationship between serum HER2 extracellular domain levels, tissue HER2
      expression, and clinico-pathological parameters in early stage breast cancer.
AB  - BACKGROUND: Measurement of human epidermal growth factor receptor 2 (HER2)
      protein in the serum of metastatic breast cancer patients has previously been
      reported, but there are no consistent data to support the clinical utility of
      serum HER2 extracellular domain for patients with early stage breast cancer. We
      aimed to evaluate the correlation between serum extracellular domain levels and
      tissue HER2 expression, and analyzed their relationship with clinico-pathological
      parameters in patients with early stage disease. METHODS: A prospective study was
      conducted on 232 breast cancer patients with stage I-III prior to treatment.
      Preoperative serum samples were measured by enzyme-linked immunosorbent assay.
      Tissue HER2 status was analyzed by immunohistochemistry and fluorescence in situ
      hybridization assays. RESULTS: The median serum extracellular domain
      concentration was 6.8 ng/ml. The best diagnostic cut-off value was 7.4 ng/ml,
      with 62.9% sensitivity and 85.3% specificity. High serum extracellular domain
      levels were reported in 89 patients (38.3%), and HER2-positive expression was
      observed in 77 patients (33.2%). Multivariate analysis showed that elevated serum
      extracellular domain correlated with postmenopausal status (P < 0.001), high
      histological grade (P < 0.001), negativity of both estrogen (P = 0.012) and
      progesterone receptors (P < 0.001), and high levels of carcinoembryonic antigen
      153 (P = 0.048). CONCLUSIONS: We recommend that 7.4 ng/ml should be used as the
      cut-off value when evaluating serum extracellular domain levels in early stage of
      breast cancer. Patients with high serum extracellular domain levels have a
      certain clinico-pathological characteristics, may provide a basis for clinical
      practice.

PMID- 23158152
TI  - MicroRNAs: important mediators of ossification.

PMID- 23158153
TI  - Bone functions as a novel endocrine organ in energy metabolism.

PMID- 23158154
TI  - Importance of bifurcation angle in bifurcation stenting.

PMID- 23158155
TI  - Interventions of side branches in the management of left ventricular dysfunction:
      a study based on the virtual dual chamber of the left ventricle.

PMID- 23158156
TI  - Matrix-induced autologous chondrocyte implantation addressing focal chondral
      defect in adolescent knee.
AB  - BACKGROUND: Matrix-induced autologous chondrocyte implantation (MACI) is the
      third generation tissue-engineering technique for the treatment of full-thickness
      articular cartilage defects. The aim of this study was to describe this new
      technique and the postoperative findings in adolescent knee with focal chondral
      defect. METHODS: The MACI consists of diagnostic arthroscopy and cartilage
      harvest, chondrocyte culture and seeding in tissue-engineering collagenous
      membrane, and implantation of the scaffold. Clinical outcome at minimum 1-year
      follow-up was assessed in seven patients (mean age (16.6 +/- 1.5) years; 14 - 19
      years) with full-thickness cartilage defects, with International Knee
      Documentation Committee (IKDC) score, the International Cartilage Repair Society
      (ICRS) score and the Knee Injury and Osteoarthritis Outcome Score (KOOS).
      Besides, MR imaging was performed with T1 and T2-weighted imaging and three
      dimensional spoiled gradient-recalled (3D-SPGR) MR imaging. RESULTS: Clinical
      evaluation showed significant improvement and MRI analysis showed that the
      structure was homogeneous and the implant surface was regular and intact in six
      patients, but irregular in one. Of all the seven patients, the cartilage defect
      site was nearly totally covered by the implanted scaffold. CONCLUSIONS: These
      results indicated that MACI technique is an option for cartilage defect in
      adolescent knee joint, especially large defect of over 2 cm(2). Long-term
      assessment is necessary to determine the true value of this technique.

PMID- 23158157
TI  - Hyper-CVAD chemotherapy or autologous stem cell transplantation in patients with
      peripheral T cell lymphomas: a single centre report.
AB  - BACKGROUND: Peripheral T-cell lymphoma (PTCL) is generally characterized by poor
      prognosis after conventional chemotherapy. The place for high-dose chemotherapy
      and autologous stem cell transplantation (ASCT) in these patients is still not
      clear. In this study, we presented the outcomes of PTCL patients followed these
      treatments in our centre. METHODS: We retrospectively analyzed the outcomes of 39
      patients with PTCL received the two treatments between 1999 and 2010. RESULTS:
      The 3-year overall survival (OS) of 61.9% and 3-year progression free survival
      (PFS) of 35.7% were observed in the 39 patient. Twenty-one patients received
      Hyper-CVAD chemotherapy with 3-year OS of 46.2% and 3-year PFS of 27.9%. Eighteen
      patients received ASCT with 3-year OS of 70.3% and 3-year PFS of 44.2%. Further
      analysis revealed that patients with elevated lactate dehydrogenase, at least 2
      international prognostic index (IPI) points, and extranodal involvement had a
      poorer outcome compared with the control group. CONCLUSION: These findings might
      suggest that Hyper-CVAD chemotherapy and ASCT could offer a durable survival
      benefit for patients with aggressive PTCL.

PMID- 23158158
TI  - Primary spinal melanoma: a case report and literature review.
AB  - This case report describes a 44-year-old woman with primary spinal cord malignant
      melanoma localized in the lumbar region. This is a very rare lesion. The patient
      presented with back pain and slight weakness in her lower extremities. Magnetic
      resonance imaging showed hyperintense signals on T1-weighted images and
      hypointense signals on T2-weighted images. The entire tumor was removed
      surgically. The patient's postoperative clinical examination revealed mild
      neurological improvements. Histopathological investigations confirmed the tumor
      was a malignant melanoma. When treating common lesions of the lumbar spinal cord
      with a benign appearance, surgeons should be aware of the potential for malignant
      tumors.

PMID- 23158159
TI  - Patient with antiphospholipid syndrome accompanied by pre-eclampsia who developed
      hellp syndrome and eclampsia after abortion.
AB  - Antiphospholipid syndrome (APS) refers to a group of clinical symptoms and signs
      caused by antiphospholipid antibody (aPLA). We reported a rare case of poor
      outcome of a pregnant woman with APS. The pregnant woman had APS, hemolytic
      anemia, elevated liver function and low platelet count (HELLP) syndrome, and
      eclampsia and had a poor outcome from a second pregnancy. She was treated with
      antispasmodics, sedatives, and anti-hypertensive agents, along with anticoagulant
      therapy and infusion of immunoglobulin. APS during pregnancy often makes
      pregnancy even more complex and risky. Obstetricians should carry out
      anticoagulation treatment throughout the perinatal period.

PMID- 23158160
TI  - Surgical guidance system and computer navigation for simultaneous femoral
      osteotomy and total knee arthroplasty for treatment of osteoarthritis associated
      with severe extra-articular deformity.

PMID- 23158161
TI  - A new cause of snapping scapula and its arthroscopic treatment.

PMID- 23158162
TI  - Ossified pseudomeningocele after laminectomy.

PMID- 23158163
TI  - Thymic carcinosarcoma consisting of sarcomatous and adenosquamous carcinomatous
      component.

PMID- 23158164
TI  - Cutaneous and systemic plasmacytosis.

PMID- 23158165
TI  - Augmented reality techniques assisted laparoscopic ureteroureterostomy for
      retrocaval ureter.

PMID- 23158166
TI  - Cochlear implantation in a patient with bilateral temporal bone fractures
      resulting from temporomandibular joint surgery.

PMID- 23158167
TI  - Development of a microfabricated device for low-voltage electropermeabilization
      of adherent cells.
AB  - A microfabricated device for low-voltage electropermeabilization of adherent
      cells has been developed. The device, which is fabricated on a cover glass using
      mainly transparent materials, allows optical observation of cells through it.
      This device consists of an array of 6-MUm circular electrodes connected via a
      transparent and conductive layer made of ITO (indium tin oxide) to give pulsed
      voltages for electropermeabilization. The surface of the electrode is coated with
      a thin Au film to reduce impedance. The insulation layer contains holes aligned
      on the electrodes to constrict the electric field so that the applied voltage
      drops mainly at the hole and is effectively used for electropermeabilization.
      Adherent cells for electropermeabilization are cultured on the device and those
      in the vicinity of the holes are influenced by the relatively strong electric
      field induced by the holes in the insulation layer. We demonstrated the culture
      of adherent cells on the device and their optical observation by phase-contrast
      microscopy. We further demonstrated the delivery of YO-PRO-1 into various cells
      including HeLa, NIH3T3, and smooth muscle cells, by applying pulsed voltages of
      6.0 V.

PMID- 23158168
TI  - [High blood pressure: objectives for 2015, an original initiative].

PMID- 23158169
TI  - Training of a thyroid surgeon: from scalpel to robot.

PMID- 23158170
TI  - Prospective evaluation of total thyroidectomy versus ipsilateral versus bilateral
      central neck dissection in patients with clinically node-negative papillary
      thyroid carcinoma.
AB  - BACKGROUND: Prophylactic central neck dissection (PCND) for papillary thyroid
      carcinoma (PTC) is controversial. We compared 3 different approaches to the
      management of central compartment nodes in patients with clinically unifocal and
      N0 PTC. METHODS: A total of 186 patients were prospectively assigned to one of
      the following procedures: total thyroidectomy (TT), TT plus ipsilateral PCND
      (Ipsi-PCND), and TT plus bilateral PCND (Bil-PCND). RESULTS: No difference was
      found concerning demographic, clinical or pathologic characteristics (P = NS).
      More patients in the Bil-PCND group had transient hypocalcemia (P < .001). One
      patient in the Bil-PCND group experienced permanent hypoparathyroidism (P = NS).
      One transient and one permanent unilateral laryngeal nerve palsy occurred in the
      Ipsi-PCND group (P = NS). Significantly more patients in the Bil-PCND and Ipsi
      PCND groups had node metastases recognized (26 vs 18 vs 6; P < .001). Six of 26
      pN1 patients (23%) in the Bil-PCND group had bilateral metastases. No difference
      was found concerning mean postoperative basal and stimulated thyroglobulin and
      mean postoperative radioiodine uptake. One patient in the Ipsi-PCND group
      experienced recurrent disease (P = NS). CONCLUSION: TT seems adequate treatment
      for most patients with clinically N0 PTC. PCND could be considered for a more
      accurate staging. Ipsi-PCND could be a valid option, but it includes the risk of
      overlooking contralateral metastases.

PMID- 23158171
TI  - Force or stratagem?

PMID- 23158172
TI  - BRAF V600E status adds incremental value to current risk classification systems
      in predicting papillary thyroid carcinoma recurrence.
AB  - BACKGROUND: Papillary thyroid cancer (PTC) recurrence risk is difficult to
      predict. No current risk classification system incorporates BRAF mutational
      status. Here, we assess the incremental value of BRAF mutational status in
      predicting PTC recurrence relative to existing recurrence risk algorithms.
      METHODS: Serial data were collected for a historical cohort having undergone
      total thyroidectomy for papillary thyroid carcinoma (PTC) during a 5-year period.
      Corresponding BRAF(V600E) testing was performed and Cox proportional hazard
      regression modeling, with and without BRAF status, was used to evaluate existing
      recurrence risk algorithms. RESULTS: The 5-year cumulative PTC recurrence
      incidence within our 356 patient cohort was 15%. A total of 205 (81%) of
      associated archived specimens were successfully genotyped, and 110 (54%) harbored
      the BRAF(V600E) mutation. The 5-year cumulative recurrence incidence among
      BRAF(V600E) patients was 20% versus 8% among BRAF wild type. BRAF(V600E) was
      significantly associated with time to recurrence when added to the following
      algorithms: AMES (hazard ratio [HR] 2.43 [confidence interval 1.08-5.49]), MACIS
      category (HR 2.46 [1.09-5.54]), AJCC-TNM (HR 2.51 [1.11-5.66]), and ATA
      recurrence-risk category (HR 2.44 [1.08-5.50]), and model discrimination improved
      (incremental c-index range 0.046-0.109). CONCLUSION: The addition of BRAF
      mutational status to established risk algorithms improves the discrimination of
      risk recurrence in patients undergoing total thyroidectomy for PTC.

PMID- 23158173
TI  - Adrenalectomy may improve cardiovascular and metabolic impairment and ameliorate
      quality of life in patients with adrenal incidentalomas and subclinical Cushing's
      syndrome.
AB  - BACKGROUND: Adrenalectomy represents the definitive treatment in clinically
      evident Cushing's syndrome; however, the most appropriate treatment for patients
      with subclinical Cushing's syndrome (SCS) with an adrenal incidentaloma remains
      controversial. This study was aimed to assess whether adrenalectomy may improve
      cardiovascular and metabolic impairment and quality of life compared with
      conservative management. METHODS: Twenty patients with adrenal incidentaloma
      underwent laparoscopic adrenalectomy for SCS, whereas 15 were managed
      conservatively. Hormonal laboratory parameters of corticosteroid secretion,
      arterial blood pressure (BP), glycometabolic profile, and quality of life (by the
      SF-36 questionnaire) were compared at baseline and the end of follow-up. RESULTS:
      The 2 groups were equivalent concerning all the examined parameters at baseline.
      In the operative group, laboratory corticosteroid parameters normalized in all
      patients but not in the conservative-management group (P < .001). In operated
      patients, a decrease in BP occurred in 53% of patients, glycometabolic control
      improved in 50%, and body mass index decreased; in contrast, no improvement or
      some worsening occurred in the conservative-management group (P < .01). SF-36
      evaluation improved in the operative group (P < .05). CONCLUSION: Adrenalectomy
      can be more beneficial than conservative management in SCS and may achieve
      remission of laboratory hormonal abnormalities and improve BP, glycemic control,
      body mass index, and quality of life.

PMID- 23158175
TI  - Robotic and endoscopic transaxillary thyroidectomies may be cost prohibitive when
      compared to standard cervical thyroidectomy: a cost analysis.
AB  - BACKGROUND: This study presents a cost analysis of the standard cervical, gasless
      transaxillary endoscopic, and gasless transaxillary robotic thyroidectomy
      approaches based on medical costs in the United States. METHODS: A retrospective
      review of 140 patients who underwent standard cervical, transaxillary endoscopic,
      or transaxillary robotic thyroidectomy at 2 tertiary centers was conducted. The
      cost model included operating room charges, anesthesia fee, consumables cost,
      equipment depreciation, and maintenance cost. Sensitivity analyses assessed
      individual cost variables. RESULTS: The mean operative times for the standard
      cervical, transaxillary endoscopic, and transaxillary robotic approaches were 121
      +/- 18.9, 185 +/- 26.0, and 166 +/- 29.4 minutes, respectively. The total cost
      for the standard cervical, transaxillary endoscopic, and transaxillary robotic
      approaches were $9,028 +/- $891, $12,505 +/- $1,222, and $13,670 +/- $1,384,
      respectively. Transaxillary approaches were significantly more expensive than the
      standard cervical technique (standard cervical/transaxillary endoscopic, P <
      .0001; standard cervical/transaxillary robotic, P < .0001; and transaxillary
      endoscopic/transaxillary robotic, P = .001). The transaxillary and standard
      cervical techniques became equivalent in cost when transaxillary endoscopic
      operative time decreased to 111 minutes and transaxillary robotic operative time
      decreased to 68 minutes. Increasing the case load did not resolve the cost
      difference. CONCLUSION: Transaxillary endoscopic and transaxillary robotic
      thyroidectomies are significantly more expensive than the standard cervical
      approach. Decreasing operative times reduces this cost difference. The greater
      expense may be prohibitive in countries with a flat reimbursement schedule.

PMID- 23158174
TI  - Differentiation of small bowel and pancreatic neuroendocrine tumors by gene
      expression profiling.
AB  - BACKGROUND: Between 10% and 20% of patients with neuroendocrine tumors (NETs)
      present with metastases of unknown primary site. Because knowledge of the primary
      site has important implications for treatment, we set out to define gene
      expression profiles to differentiate between small-bowel NETs (SBNETs) and
      pancreatic NETs (PNETs). METHODS: RNA was extracted from tumor and normal tissues
      in 11 patients with SBNETs and 15 patients with PNETs, and qPCR was performed for
      367 GPCR genes. Differentially expressed genes were identified using the RT2
      Profiler. Whole genome expression analysis was performed on 11 SBNETs, 5 PNETS,
      and corresponding normal tissues. Statistical significance was evaluated by the
      Student t test and ANOVA. RESULTS: Whole-genome analysis revealed 173
      significantly differentially expressed genes in SBNETs and normal tissues and in
      52 in PNETs. GPCR arrays identified 28 genes in SBNETs and 18 in PNETs, with
      significant expression differences from normal tissues. In all SBNETs, 2 genes
      were significantly upregulated by more than fivefold: OXTR and GPR113. No PNETs
      shared this profile, whereas 73% had a greater than fivefold downregulation of
      ADORA1 and SCTR. These genes also allowed for determination of the primary site
      in 8 of 10 liver metastases. CONCLUSION: Differential expression patterns using
      as few as 2 to 4 GPCR genes successfully discriminated primary sites in small
      bowel and pancreatic NETs.

PMID- 23158176
TI  - Why I have abandoned robot-assisted transaxillary thyroid surgery.

PMID- 23158177
TI  - Utility of oral nicardipine and magnesium sulfate infusion during preparation and
      resection of pheochromocytomas.
AB  - BACKGROUND: Calcium channel blockade with nicardipine (NC) is an alternative to
      phenoxybenzamine (PB) preparation for resection of a pheochromocytoma.
      Intraoperative magnesium sulfate infusion (+MgSO(4)) is often used for its
      cardiovascular stabilizing properties. We hypothesized that preparation with NC
      would be similar clinically to PB for resection of a pheochromocytoma, and
      MgSO(4) infusion would not affect intraoperative stability. METHODS: This
      retrospective review included 64 patients undergoing resections of a
      pheochromocytoma from 2003 to 2011. PB or NC was used preoperatively, with
      MgSO(4) use distributed equally in the population. Pre-, intra-, and
      postoperative hemodynamics and outcomes were compared. RESULTS: There was no
      difference in NC (n = 7) versus PB (n = 57) or +MgSO(4) (n = 33) versus -MgSO(4)
      (n = 31) groups for demographics with the exception of age. The NC group had
      smaller median tumor size and lesser plasma baseline levels of normetanephrine
      than the PB group, but subgroup analysis of all neoplasms <3.0 cm revealed no
      differences. Pre-, intra- and postoperative hemodynamic stability and outcomes
      were similar for NC versus PB analyses as well as the +MgSO(4) versus -MgSO(4)
      groups. CONCLUSION: NC use may be an equivalent alternative to PB in preoperative
      preparation, especially for smaller pheochromocytomas. Intraoperative MgSO(4) use
      does not seem to have a substantive effect on hemodynamic stability.

PMID- 23158178
TI  - Thyroidectomy followed by fosbretabulin (CA4P) combination regimen appears to
      suggest improvement in patient survival in anaplastic thyroid cancer.
AB  - BACKGROUND: Anaplastic thyroid cancer (ATC) is an aggressive neoplasm for which a
      paucity of data exist about the relative role of operative procedures in disease
      management. METHODS: The FACT trial was a randomized, controlled phase 2/3 trial
      assessing the safety and efficacy of carboplatin/paclitaxel with CA4P
      (experimental arm) or without CA4P (control arm) in ATC, 2007-11. Patients were
      permitted to have had an operation before enrollment, which was stratified on the
      basis of exposure to operation. A subpopulation of patients who had a cancer
      related operation (thyroidectomy) was compared with those who did not, and 1-year
      and median survival were estimated. RESULTS: A total of 80 patients were
      enrolled; 55% had undergone a cancer-related operation, of whom 70% had near
      total/total thyroidectomy. Baseline characteristics for operative and
      nonoperative patients were not substantially different. Median survival for
      patients who had cancer-related operation was 8.2 months in the CA4P arm versus
      4.0 months in the control arm, resulting in a hazard ratio of 0.66 (P = .25) and
      a suggested associated reduction in risk of death of 35%. 1-year survival was
      33.3% in the CA4P arm versus 7.7% in the control arm. CONCLUSION: In this largest
      prospective study ever conducted in ATC, thyroidectomy followed by CA4P
      combination regimen showed a nonsignificant trend toward improvement in patient
      survival.

PMID- 23158179
TI  - Anaplastic thyroid cancer: rare, fatal, and neglected.

PMID- 23158180
TI  - Laparoscopic versus open adrenalectomy: another look at outcome using the Clavien
      classification system.
AB  - BACKGROUND: A laparoscopic approach to adrenalectomy has become the procedure of
      choice for most adrenal resections. We hypothesized that laparoscopic
      adrenalectomy is less likely to result in intensive care unit (ICU) level
      complications or death than open adrenalectomy, despite baseline comorbidity mix.
      METHODS: Using the National Surgical Quality Improvement Program (NSQIP)
      participant use files for 2005-2009, all laparoscopic and open adrenalectomies
      were identified by current procedural terminology. Adverse outcomes tracked in
      NSQIP were mapped to Clavien level based on need for ICU care or death.
      Univariate and multivariate analysis were used to compare groups. RESULTS: There
      were 1,980 laparoscopic and 592 open procedures. Clavien 4 and 5 complications
      occurred in 45 (7.6%) of open and 35 (1.8%) of laparoscopic operations. The
      univariate odds ratio showed a 4.6-fold greater likelihood that a patient would
      have an ICU level complication (P < .001), and 4.9 odds ratio of death (P < .001)
      if an open rather than laparoscopic operation was performed. Regression modeling
      showed persistence of the protective effect of laparoscopy after adjusting for
      comorbidities with a multivariate odds ratio of 3.3 (P < .001). CONCLUSION: The
      laparoscopic approach to adrenalectomy has an independent protective effect on
      ICU level complications and mortality when compared with open procedures. This
      correlation persists after correcting for multiple comorbidities.

PMID- 23158181
TI  - Undetectable thyroglobulin after total thyroidectomy in patients with low- and
      intermediate-risk papillary thyroid cancer--is there a need for radioactive
      iodine therapy?
AB  - BACKGROUND: The efficacy of radioactive iodine therapy (RAI) in patients who have
      an undetectable thyroglobulin (Tg) level after total thyroidectomy in well
      differentiated papillary thyroid cancer (PTC) is questionable. The objectives of
      this study were to report the risk of recurrence in patients with PTC who had an
      undetectable Tg level after total thyroidectomy managed with postoperative RAI
      and without RAI. METHODS: After approval by the institutional review board, 751
      consecutive patients who had total thyroidectomy for PTC as well as postoperative
      Tg measurement were identified from our institutional database of 1163 patients
      treated for well-differentiated thyroid carcinoma at Memorial Sloan Kettering
      Cancer Center between 1999 and 2005. Of these, 424 patients had an undetectable
      postoperative Tg (defined as a Tg <1 ng/mL) of whom 80 were classified as low,
      218 intermediate, and 126 high risk via use of the GAMES (grade, age, distant
      metastasis, extrathyroidal extension, and size of the neoplasm) criteria.
      Patient, neoplasm, and treatment characteristics were recorded on the low- and
      intermediate-risk patients. Recurrence was defined as any structural abnormality
      on examination or imaging and confirmed by fine-needle aspiration biopsy. Disease
      specific survival and recurrence-free survival (RFS) were calculated with the
      Kaplan-Meier method. Univariate analysis was carried out by the log rank test and
      multivariate analysis by Cox proportional hazards method. RESULTS: In the low
      risk group (n = 80), 35 patients received postoperative RAI and 45 did not.
      Comparison of patient and tumor characteristics showed patients treated without
      RAI were more likely to have T1 tumors (82% vs 60%, P = .027). There were no
      disease-specific deaths in either group. There was 1 neck recurrence in the group
      that did not receive RAI. Patients managed without RAI had a similar RFS to
      patients managed with RAI (96% vs 100%, P = .337). In the intermediate risk group
      (n = 218), 135 were managed with RAI and 83 without. Comparison of patient and
      tumor characteristics showed patients managed without RAI were more likely to be
      older patients (>= 45 years: 90% vs 39%, P < .0005) with smaller tumors (pT1T2:
      97% vs 62%, P < .0005) and negative neck disease (N0: 56% vs 30%, P < .0005).
      There were no disease specific deaths in either group. There were 7 recurrences,
      of which 6 were in the RAI cohort (5 regional, 1 distant) and 1 in the non-RAI
      cohort (1 regional). Patients managed without RAI had a similar RFS to patients
      managed with RAI (97% vs 96%, P = .234). CONCLUSION: Select low- and intermediate
      risk group patients who have undetectable Tg after total thyroidectomy for PTC
      can be managed safely without adjuvant RAI with no increase in risk of
      recurrence.

PMID- 23158182
TI  - Metabolomics approach to thyroid nodules: a high-resolution magic-angle spinning
      nuclear magnetic resonance-based study.
AB  - BACKGROUND: Proton magnetic resonance spectroscopy of operative specimens has
      been reported to successfully differentiate normal tissue from malignant thyroid
      tissue. We used a new high-resolution magnetic resonance spectroscopy technique
      for the differentiation of benign and malignant thyroid neoplasms. METHODS:
      Histological specimens from 72 patients undergoing a total thyroidectomy were
      processed into a 4-mm ZrO(2) high-resolution magic angle spinning (HRMAS) rotor
      with 5 MUL of D(2)O. A Bruker Avance spectrometer operating at 400 MHz for the
      (1)H frequency and equipped with a (1)H/(13)C/(31)P HRMAS probe was used.
      RESULTS: Normal and neoplastic thyroid tissues could be discriminated from each
      other by different relative concentrations of several amino acids and lipids, as
      well as benign and malignant neoplasms, that differed in terms of a greater
      lactate and taurine and a lesser lipid choline, phosphocholine, myo-inositol, and
      scyllo-inositol levels in malignant samples. A statistical analysis with a
      receiver operating characteristic curve revealed that 77% of the samples were
      accurately predicted. Similar results were obtained with specimens obtained from
      ex vivo aspirates. CONCLUSION: A further development of this project will be to
      use the metabolomics approach on specimens obtained from aspirates in vivo after
      the resolution of technical problems attributable to possible contamination.

PMID- 23158183
TI  - Same-day thyroidectomy program: eligibility and safety evaluation.
AB  - BACKGROUND: Same-day thyroidectomy has not gained widespread acceptance owing to
      concerns of life-threatening complications. The aim of this study is to describe
      a single institution same-day thyroidectomy results. METHODS: We included
      patients who underwent thyroid surgery between 2005 and 2011 by a single surgeon.
      The outcomes of patients who underwent inpatient (IP) and same-day thyroidectomy
      were compared. Routine postoperative parathyroid hormone testing for same-day
      thyroidectomy commenced in 2010, and results were also compared after that date.
      RESULTS: Thyroid surgery was performed in 608 patients; 298 (49%) were performed
      as same-day thyroidectomy. Patients undergoing same-day thyroid lobectomy had
      similar, low documented complication rate as IP lobectomy. Patients with same-day
      total thyroidectomy (SDTT) had similar rates of documented transient hypocalcemia
      and neck hematoma compared with IPs. After 2010, all patients without restrictive
      underlying comorbidities were scheduled for same-day thyroidectomy unless
      otherwise specifically requested by the patient. Only 4 (3%) patients scheduled
      for SDTT were converted to IPs, all without neck complications. CONCLUSION: Same
      day thyroidectomy is safe and can be routinely performed by experienced surgeons
      who have low complication rates and a patient support system.

PMID- 23158184
TI  - Autophagic activation potentiates the antiproliferative effects of tyrosine
      kinase inhibitors in medullary thyroid cancer.
AB  - BACKGROUND: We hypothesized that autophagy inhibition would enhance the
      anticancer efficacy of ret protooncogene-targeted therapy in medullary thyroid
      cancer. METHODS: Medullary thyroid cancer-1.1 and TT cells were treated with
      sunitinib or sorafenib in the presence or absence of everolimus, trehalose, or
      small interfering RNA directed against autophagy protein 5. RESULTS: Sunitinib
      and sorafenib each robustly induced light chain 3-II expression, indicating
      autophagy activation. Autophagy protein 5 silencing diminished the
      antiproliferative effects of sunitinib and sorafenib by 44% (P < .05) and 41% (P
      < .05), respectively, in medullary thyroid cancer-1.1 cells and by 43% (P < .01)
      and 39% (P < .05), respectively, in TT cells. In contrast, everolimus increased
      the antiproliferative effects of sunitinib and sorafenib by 24% (P < .01) and 27%
      (P < .01), respectively, in medullary thyroid cancer-1.1 cells and by 20% (P <
      .05) and 23% (P < .05), respectively, in TT cells. Trehalose increased the
      antiproliferative effects of sunitinib and sorafenib by 26% (P < .01) and 27% (P
      < .01), respectively, in medullary thyroid cancer-1.1 cells and by 28% (P < .05)
      and 29% (P < .05), respectively, in TT cells. Autophagy protein 5 silencing
      abrogated both everolimus- and trehalose-induced increases in tyrosine kinase
      inhibitor efficacy. CONCLUSION: Loss (gain) of autophagy diminishes (improves)
      the efficacy of sunitinib and sorafenib. Our findings suggest that autophagic
      activation should be combined with targeted ret protooncogene therapy for
      patients with advanced medullary thyroid cancer.

PMID- 23158185
TI  - Resection of adrenocortical carcinoma is less complete and local recurrence
      occurs sooner and more often after laparoscopic adrenalectomy than after open
      adrenalectomy.
AB  - BACKGROUND: Controversy surrounds the use of laparoscopy for resection of
      adrenocortical carcinoma. We evaluated the hypothesis that outcome is equivalent
      in patients undergoing laparoscopic adrenalectomy versus open adrenalectomy.
      METHODS: This is a retrospective review of 217 patients (156 patients with stage
      I-III cancer) with adrenocortical carcinoma referred to a single institution
      between 2005 and 2011. Outcome and operative data were assessed for the subset
      undergoing resection with curative intent. Student t and Fisher exact tests and
      the Kaplan-Meier method were used to compare data (P <= .05 was considered
      statistically significant). RESULTS: One hundred fifty-six patients (64% female;
      median age, 47 years [range, 18-80]; median follow-up, 26.5 months [range, 1
      188]) were identified. Forty-six patients underwent laparoscopic adrenalectomy,
      and 110 underwent open adrenalectomy. Twenty-seven percent of laparoscopic
      adrenalectomy patients had stage III cancer. After laparoscopic adrenalectomy,
      30% had positive margins or intraoperative tumor spill compared to 16% of the
      open adrenalectomy patients (P = .04). Overall survival for patients with stage
      II cancer was longer in those undergoing open adrenalectomy (P = .002). Time to
      visible tumor bed recurrence or peritoneal recurrence in stage II patients was
      shorter in laparoscopic adrenalectomy patients (P = .002). CONCLUSION: Open
      adrenalectomy is superior to laparoscopic adrenalectomy for adrenocortical
      carcinoma based on completeness of resection, site and timing of initial tumor
      recurrence, and survival in stage II patients. Intraoperative evaluation is
      insensitive for the detection of stage III tumors.

PMID- 23158186
TI  - Long-term follow-up data may help manage patient and parent expectations for
      pediatric patients undergoing thyroidectomy.
AB  - BACKGROUND: We investigated the incidence and impact of postoperative
      complications in children who underwent total thyroidectomy (TTx). METHODS: The
      records of all pediatric patients undergoing TTx (2001-2011) at our institution
      were retrospectively reviewed for the occurrence of biochemical hypothyroidism
      (thyroid-stimulating hormone >10 mIU/mL), laboratory assessments, and medication
      nonadherence. RESULTS: The 74 patients (median age, 12.5 years) had thyroid
      cancer (differentiated, n = 39; medullary, n = 16) or benign pathology (n = 19;
      16 with multiple endocrine neoplasia type 2A). The median postoperative follow-up
      was 3.2 years; 46 patients (62%) had >= 1 year follow-up. Forty-one percent had
      >= 1 period of medication nonadherence; this was not associated with age at TTx
      (P = .30). Non-treatment-related hypothyroidism occurred in 33% of patients
      during postoperative year (POY) 1. The number of POY1 laboratory assessments
      among the 30% of patients with parathyroid dysfunction was more than twice that
      among patients with normal parathyroid function (median assessments per year 8 vs
      3; P < .0001). Forty-four percent of patients/families reported behavioral or
      physiologic changes; 40% were concomitant with abnormal thyroid function.
      CONCLUSION: More than 40% of pediatric patients were unable to fully adhere to
      postoperative medication regimens, and non-treatment-related hypothyroidism was
      common. Postoperative hypoparathyroidism doubled the number of laboratory
      assessments obtained. These data may help families better prepare for TTx
      sequelae.

PMID- 23158187
TI  - Should patients with Cowden syndrome undergo prophylactic thyroidectomy?
AB  - BACKGROUND: Cowden syndrome (CS) is dominantly inherited and predisposes patients
      to tumors in multiple organs. We characterized CS-associated malignant and benign
      thyroid disease. METHODS: Of data from 3,477 prospectively recruited CS patients
      with known genetic analysis, we analyzed 225 PTEN mutation+ patients whose
      treatment occurred at our center (n = 25) or other hospitals nationwide (n =
      200). RESULTS: A total of 32 of 225 PTEN mutation+ patients (14%) had thyroid
      cancer: 52% papillary, 28% follicular-variant papillary, 14% follicular, and 6%
      anaplastic. Median age at diagnosis was 35 years compared with 49 years for
      Surveillance Epidemiology and End Results population data. Initial thyroid
      ultrasonography in 16 of 25 patients revealed thyroiditis/goiters in all >13
      years age, leading to FNA in 7 (64%), thyroidectomy in 3 (27%), and new cancer
      diagnosis in 2 (18%). Three with severe autism required intraoperative sedation
      for ultrasonography. A total of 9 of 25 patients were monitored after multiple
      partial thyroidectomies for goiters by age 42 (n = 5), thyroiditis, or cancer
      detected by age 36 (n = 3). CONCLUSION: PTEN mutation+ patients with CS have an
      enormous prevalence of thyroid disease. Earlier screening may be advisable
      because thyroiditis and nodules are seen by the time patients reach adolescence,
      and cancer diagnosis occurs on average 14 years earlier than expected.
      Furthermore, the risks observed may justify prophylactic total thyroidectomy in
      select, if not all, patients, particularly those with developmental disorders.

PMID- 23158188
TI  - Invasion in follicular thyroid cancer cell lines is mediated by EphA2 and pAkt.
AB  - BACKGROUND: EphA2 is a tyrosine kinase receptor that is overexpressed in many
      cancers and is associated with poor prognosis and increased metastasis.
      Phosphorylated Akt (pAkt) plays a role in the regulation of thyroid cancer
      invasion and metastasis. We investigated the role of EphA2 and Akt in FTC-133 and
      FTC-238, 2 closely related human cell lines with differing invasive phenotypes.
      METHODS: Western blot was used to measure the total protein expression in cell
      lines, and immunohistochemistry was performed on thyroid tissue microarrays.
      Thyroid cell lines were transfected with siRNA or cDNA. Invasion assays were
      performed using Matrigel chambers, and invaded cells were assayed with (3
      (4,5dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide (MTT). RESULTS: EphA2
      protein was expressed in thyroid cancer cell lines and in benign and malignant
      human thyroid tumors but not in normal thyroid. Compared with FTC-133, FTC-238
      expressed fivefold more EphA2 protein and had a fivefold increase in invasion (P
      < .001). In FTC-238, EphA2 siRNA decreased EphA2 levels and reduced invasion,
      with a decrease in pAkt protein. Overexpression of EphA2 in FTC-133 increased
      invasion and increased pAkt protein. Akt siRNA and Akt inhibitors decreased pAkt
      levels and invasion without changing EphA2 levels. CONCLUSION: EphA2 is expressed
      in human thyroid cancer and mediates invasion in the follicular thyroid cell
      lines FTC-133 and -238. Phosphorylated Akt (pAkt), an important regulator of
      thyroid cancer metastasis, is attenuated by EphA2 knockdown, providing evidence
      that EphA2 may act through pAkt to mediate invasion. EphA2 and pAkt may be
      candidates for targeted therapy against metastatic thyroid cancer.

PMID- 23158189
TI  - Symptoms of gastroesophageal reflux disease improve after parathyroidectomy.
AB  - BACKGROUND: Primary hyperparathyroidism can be associated with symptoms related
      to GERD, but it is unclear which symptoms of GERD improve after
      parathyroidectomy. Our goal was to assess prospectively for changes in specific
      GERD symptoms after parathyroidectomy using a validated questionnaire. METHODS:
      Using the GERD health-related quality of life (GERD-HRQL) questionnaire, symptoms
      of heartburn were prospectively assessed before and 6 months after treatment of
      hyperparathyroidism with parathyroidectomy. This validated questionnaire includes
      10 items, with a Likert scale of 0-5. Scores range from 0 to 45, a lesser score
      indicates fewer/less severe symptoms. RESULTS: Pre- and postoperative surveys
      were available for 51 patients. Parathyroidectomy improved the overall
      questionnaire score (12.5 +/- 1.3 vs 4.5 +/- 0.9, P < .0001). Overall scores for
      each question improved after parathyroidectomy, including symptoms of dysphagia
      (P = .001) and overall satisfaction with symptoms (P < .0001). However, the
      number of patients taking antireflux medication before and after
      parathyroidectomy was not substantially different (34 vs 28 patients, P = .17).
      CONCLUSION: All symptoms of GERD improved after parathyroidectomy for
      hyperparathyroidism. Despite the decrease in symptoms, there was not a change in
      the number of patients who remained on anti-reflux therapy. For patients with
      symptoms of GERD, a trial off antireflux medications after parathyroidectomy
      should be considered.

PMID- 23158190
TI  - Novel withanolides target medullary thyroid cancer through inhibition of both RET
      phosphorylation and the mammalian target of rapamycin pathway.
AB  - BACKGROUND: Despite development of current targeted therapies for medullary
      thyroid cancer (MTC), long-term survival remains unchanged. Recently isolated
      novel withanolide compounds from Solanaceae physalis are highly potent against
      MTCs. We hypothesize that these withanolides uniquely inhibit RET phosphorylation
      and the mammalian target of rapamycin (mTOR) pathway in MTC cells as a mechanism
      of antiproliferation and apoptosis. METHODS: MTC cells were treated with novel
      withanolides and MTC-targeted drugs. In vitro studies assessed cell viability and
      proliferation (MTS; trypan blue assays), apoptosis (flow cytometry with Annexin
      V/PI staining; confirmed by Western blot analysis), long-term cytotoxic effects
      (clonogenic assay), and suppression of key regulatory proteins such as RET, Akt,
      and mTOR (by Western blot analysis). RESULTS: The novel withanolides potently
      reduced MTC cell viability (half maximal inhibitory concentration [IC(50)], 270
      2,850 nmol/L; 250-1,380 nmol/L for vandetanib; 360-1,640 nmol/L for cabozantinib)
      with induction of apoptosis at <1,000 nmol/L of drug. Unique from other targeted
      therapies, withanolides suppressed RET and Akt phosphorylation and protein
      expression (in a concentration- and time-dependent manner) as well as mTOR
      activity and translational activity of 4E-BP1 and protein synthesis mediated by
      p70S6kinase activation at IC(50) concentrations. CONCLUSION: Novel withanolides
      from Physalis selectively and potently inhibit MTC cells in vitro. Unlike other
      MTC-targeted therapies, these compounds uniquely inhibit both RET kinase activity
      and the Akt/mTOR prosurvival pathway. Further translational studies are warranted
      to evaluate their clinical potential.

PMID- 23158191
TI  - Unilateral adrenal hyperplasia: a novel cause of surgically correctable primary
      hyperaldosteronism.
AB  - BACKGROUND: Primary hyperaldosteronism may be caused by an aldosterone-producing
      adenoma (APA), which is correctable by unilateral adrenalectomy or by idiopathic
      adrenal hyperplasia, a bilateral disease without any indication for surgery. This
      study sought to assess the prevalence and the results of surgery in unilateral
      adrenal hyperplasia (UAH). METHODS: The study included 35 patients who underwent
      unilateral adrenalectomy because of primary hyperaldosteronism after unequivocal
      successful lateralization by adrenal venous sampling. Demographics, biochemical
      evaluation, and blood pressure were assessed pre- and postoperatively. Pathology
      was categorized as APA (isolated adenoma), nodular (multiple micromacronodules),
      and diffuse UAH (gland thickening without nodules). RESULTS: Pathology revealed 9
      APAs and 23 nodular and 3 diffuse UAHs. Patients with APAs and UAHs were
      statistically similar regarding demographics and preoperative blood pressure
      levels. Bilateral adrenal involvement was evident at imaging in 10 patients (11%
      in APA versus 35% in UAH, P = NS). After surgery, biochemical cure of the disease
      was achieved in all patients; blood pressure levels normalized in 66.6% of
      patients and ameliorated in 22.2% in APA versus 34.6% and 50% in patients with
      UAH (P = NS). At a long-term follow-up, only 1 patient with nodular UAH
      experienced a biochemical recurrence of disease. CONCLUSION: UAH is not rare,
      sharing the same features of APA. When disease lateralization is confirmed by
      adrenal venous sampling, unilateral adrenalectomy achieves excellent long-term
      results.

PMID- 23158192
TI  - Tumor-induced osteomalacia masking primary hyperparathyroidism.

PMID- 23158194
TI  - Transitions, reflections, and welcome.

PMID- 23158193
TI  - Frequent alcohol drinking is associated with lower prevalence of self-reported
      common cold: a retrospective study.
AB  - BACKGROUND: Alcohol intake has been associated with reduced incidence of common
      cold symptoms in 2 European studies. However, no study has addressed the
      association between the frequency of alcohol intake and the incidence of common
      cold. This study aimed to investigate the association between the amount and
      frequency of alcohol drinking and the retrospective prevalence of common cold in
      Japanese men. METHODS: This retrospective study included men who participated in
      an annual health examination conducted in Sendai, Japan. The frequency of common
      cold episodes in the previous year was self-reported. The weekly frequency and
      amount of alcohol consumed, as well as the type of alcoholic drink, were reported
      by a brief-type self-administered diet history questionnaire. Logistic regression
      models were used to analyze the association between the amount and frequency of
      alcohol intake and the retrospective prevalence of common cold. RESULTS: Among
      899 men, 83.4% of the subjects reported drinking alcohol, and 55.4% of the
      subjects reported having experienced at least one episode of common cold in the
      previous year. Compared with non-drinkers, the adjusted odds ratios (ORs) with
      95% confidence intervals (CIs) for having had 1 or more episodes of common cold
      during the past year across categories of alcohol intake frequency of 3 or less,
      4-6, and 7 days/week were 0.827 (0.541-1.266), 0.703 (0.439-1.124), and 0.621
      (0.400-0.965), respectively (P for trend = 0.025); the adjusted ORs with 95% CIs
      for having had of 2 or more episodes of common cold across the same categories
      were 0.642 (0.395-1.045), 0.557 (0.319-0.973), and 0.461 (0.270-0.787),
      respectively (P for trend = 0.006). Compared with subjects who consumed 11.5-35.8
      g of alcohol per day, the non-drinkers were significantly more likely to
      experience 2 or more episodes of common cold (OR, 1.843; 95% CI, 1.115-3.047).
      CONCLUSION: The frequency, not the amount, of alcohol intake was significantly
      related to lower prevalence of self-reported common cold episodes in Japanese
      men.

PMID- 23158195
TI  - Academic practice partnerships: a national dialogue.
AB  - Academic-practice partnerships are an important mechanism to strengthen nursing
      practice and help nurses become well positioned to lead change and advance
      health. Through implementing such partnerships, both academic institutions and
      practice settings will formally address the recommendations of the Institute of
      Medicine Future of Nursing Committee. Effective partnerships will create systems
      for nurses to achieve educational and career advancement, prepare nurses of the
      future to practice and lead, provide mechanisms for lifelong learning, and
      provide a structure for nurse residency programs. This paper details the work of
      the American Association of Colleges of Nursing-American Organization of Nurse
      Executives Task Force on Academic-Practice Partnerships that has identified
      hallmarks of successful partnership and produced tools and shared exemplars to
      assist nursing leaders in developing and sustaining partnerships for the future.

PMID- 23158196
TI  - Charting the course for nurses' achievement of higher education levels.
AB  - To improve patient outcomes and meet the challenges of the U.S. health care
      system, the Institute of Medicine recommends higher educational attainment for
      the nursing workforce. Characteristics of registered nurses (RNs) who pursue
      additional education are poorly understood, and this information is critical to
      planning long-term strategies for U.S. nursing education. To identify factors
      predicting enrollment and completion of an additional degree among those with an
      associate or bachelor's as their pre-RN licensure degree, we performed logistic
      regression analysis on data from an ongoing nationally representative panel study
      following the career trajectories of newly licensed RNs. For associate degree
      RNs, predictors of obtaining a bachelor's degree are the following: being Black,
      living in a rural area, nonnursing work experience, higher positive affectivity,
      higher work motivation, working in the intensive care unit, and working the day
      shift. For bachelor's RNs, predictors of completing a master's degree are the
      following: being Black, nonnursing work experience, holding more than one job,
      working the day shift, working voluntary overtime, lower intent to stay at
      current employer, and higher work motivation. Mobilizing the nurse workforce
      toward higher education requires integrated efforts from policy makers,
      philanthropists, employers, and educators to mitigate the barriers to continuing
      education.

PMID- 23158197
TI  - A dedicated education unit VA medical centers and baccalaureate nursing programs
      partnership model.
AB  - A shortage of qualified nurse faculty and limitations in the number and variety
      of available clinical facilities have impacted the ability of schools of nursing
      to offer quality clinical education. Dedicated education units involving
      partnerships between academia and clinical agencies have been proposed as 1
      solution to these challenges. The purpose of this article is to describe a
      dedicated education unit model developed in a partnership between 2 Veterans
      Health Administration Medical Centers and 2 midwestern university schools of
      nursing. A review of the literature related to dedicated education units is
      shared. Implementation strategies and benefits to the clinical sites and the
      schools of nursing are discussed.

PMID- 23158198
TI  - Development of scholarly trajectories that reflect core values and priorities: a
      strategy for promoting faculty retention.
AB  - Development of scholarly trajectories that more adequately allow faculty to
      balance work-related goals with priorities in their larger lives may play an
      important role in the retention of nursing faculty. This article articulates a
      process for developing scholarly trajectories consistent with core values and
      priorities. The potential of Boyer's model of scholarship as a framework for such
      a trajectory is discussed. Attention is given to consciously think through
      competing priorities within and across the multiple facets of life as a critical
      component of staging academic pursuits. An exercise designed to enhance creation
      of scholarly trajectories that balance needs across different dimensions is
      presented. Challenges affecting development of scholarly trajectories, including
      increased scholarly demands, growing preference for doctorally prepared faculty,
      and tenure/promotion expectations and time frames, are addressed.

PMID- 23158199
TI  - The missing link: using emotional intelligence to reduce workplace stress and
      workplace violence in our nursing and other health care professions.
AB  - Because of our poor emotionally intelligent responses and interactions, many
      nurses and other health care staff have become scarred emotionally from abusive,
      demoralizing, or hostile acts inflicted on one another. Rude, disruptive behavior
      among health care professionals can pose a serious threat to patient safety and
      the overall quality of care. The expectation of regulating bodies is that health
      care professionals focus on effects disruptive behavior has on a culture of
      safety for both patients and staff. Relatively recent research in training and
      development, and behavior change, specifically on emotional intelligence,
      suggests that it is possible to improve the emotional competence of adults. I
      posit it is possible to increase emotional competence to reduce health workplace
      stress and workplace violence.

PMID- 23158200
TI  - A comparative analysis of master of nursing students' scholarly inquiry.
AB  - Although graduates of master's of nursing programs are expected to demonstrate
      competence in systematic inquiry, few reports describe how students obtain this
      skill. We conducted a comparative analysis of 118 scholarly projects from 2004 to
      2009 with an earlier sample of 112 projects from 1996 to 2003. We examined
      changes in the method of scholarly inquiry, population type examined, and
      outcomes or products of inquiry. Data from a scholarly inquiry evaluation
      checklist were transcribed and analyzed. Literature review continued to be the
      most frequent method of scholarly inquiry, with few group differences noted
      between the time periods. Evidence-based clinical or practice projects increased
      as an inquiry method, as did health care providers as the population type. Papers
      of publishable quality and educational materials increased as outcomes of
      scholarly inquiry. Although this analysis is limited by incomplete data and a
      need to clarify checklist categories, the increased number of clinical-based
      projects supports a shift to evidence-based practice outcomes. The expansion in
      the number of educational scholarly projects is attributed to increasing
      enrollment in the nurse educator option. With new Essentials of Master's
      Education in Nursing and the transition of specialty preparation to the doctoral
      level, revisiting scholarly outcomes for master's degree students is recommended.

PMID- 23158201
TI  - Regionally increasing baccalaureate-prepared nurses: development of the RIBN
      model.
AB  - The nursing shortage remains an acute problem at the national level and
      significantly endangers the provision of safe and effective health care. One of
      the most significant problems fueling the nursing shortage in the United States
      is the lack of faculty to educate the number of qualified individuals applying to
      nursing programs. A major factor driving the shortage of faculty emanates from
      the current trend in basic nursing education that is increasing the proportion of
      nurses with an associate degree in nursing (ADN) as their terminal professional
      education. Community colleges, that offer the associate degree, play a crucial
      role in providing access to nursing education. However, they now account for more
      than 2/3 of all new nursing graduates in the United States. With over 2/3 of our
      new nurses completing only associate degree programs, the faculty pipeline
      continues to decrease. This also means fewer bachelor of science in nursing (BSN)
      and higher-degree-prepared nurses available for advanced clinical practice,
      management roles, and public health services. It is therefore critical to
      identify and implement new pathways to increase the number of ADN graduates who
      complete baccalaureate education and, thereby, increase the percentage of BSN
      prepared nurses. This article describes the development and implementation of a
      model in North Carolina to regionally increase the number of baccalaureate
      prepared nurses through the development of partnerships between community
      colleges and universities.

PMID- 23158202
TI  - An analysis of Richard Prince's "Lake Resort Nurse": using an image to expose and
      critically reflect on stereotypes in nursing.
AB  - Our interactions with images, created and viewed within contexts, are a
      significant means through which we construct and interpret our values and
      beliefs. Nurses' efforts at monitoring images to encourage accurate portrayals of
      nurses' work have had little influence on the way nurses are represented or the
      inherent ability of images to shape perceptions of nurses' work. One explanation
      for this lack of influence is that viewers do not closely attend to the ways in
      which we make meaning of everyday images. This inattention creates passive
      viewers, vulnerable to and more likely to internalize messages (G. Dines & J.
      Humez, 2011). Misunderstandings about nursing leave nurses vulnerable to contexts
      and influence the outcomes of at least 2 issues, the nursing shortage and the
      provision of quality care. Prince, in his painting "Lake Resort Nurse," utilizes
      the artistic strategies of expressionism, appropriation, and reflexivity to
      expose stereotypes and provides an opportunity for reflection on the potential
      impact these stereotypes have on the profession. He provides a means through
      which we can recognize that images are significant contributors to how
      understandings of nursing and nurses are shaped. New understandings of nursing,
      gained through reflection and dialog, subsequently influences perceptions of the
      value of nurses' work and their contribution to health care.

PMID- 23158203
TI  - Does ibuprofen prevent acute mountain sickness?

PMID- 23158204
TI  - Wilderness Medical Society practice guidelines for treatment of eye injuries and
      illnesses in the wilderness.
AB  - A panel convened to develop an evidence-based set of guidelines for the
      recognition and treatment of eye injuries and illnesses that may occur in the
      wilderness. These guidelines are meant to serve as a tool to help wilderness
      providers accurately identify and subsequently treat or evacuate for a variety of
      ophthalmologic complaints. Recommendations are graded based on the quality of
      their supporting evidence and the balance between risks and benefits according to
      criteria developed by the American College of Chest Physicians.

PMID- 23158205
TI  - Interventions to reduce antipsychotic polypharmacy: a systematic review.
AB  - BACKGROUND: It still remains unclear as to how to counteract antipsychotic
      polypharmacy that remains controversial but common. The objective of this study
      was to synthesize the clinical evidence to reduce antipsychotic polypharmacy
      (i.e. use of multiple antipsychotics) in schizophrenia. METHODS: A literature
      search was performed to identify clinical trials that attempted to reduce
      antipsychotic polypharmacy in patients with schizophrenia by any form of
      systematic intervention using PubMed as well as MEDLINE, EMBASE, and PsycINFO
      (last search: June 2012). The search terms included "antipsychotics" and
      "polypharmacy". Cross-referencing was also performed. RESULTS: The literature
      search identified 17 studies. Only 3 studies (1 randomized controlled trial and 2
      open-label trials) were found that systematically switched antipsychotic
      polypharmacy to monotherapy. In two of them, more than two thirds of the subjects
      successfully completed the switch (40/58, 69.0%; 34/44, and 77.3%, respectively)
      while less than half the subjects tolerated it in the other study (6/14 and
      42.9%) although the sample size was very small. On the other hand, 14 studies
      that examined impacts of interventions have physicians refrain from antipsychotic
      polypharmacy. While a modest intervention with educational approach alone was
      effective in three of the five articles, a more assertive intervention that
      directly cautioned physicians on the use of polypharmacy was effective in 10 of
      12 articles. CONCLUSION: The literature search revealed the paucity of the data.
      Careful switching from polypharmacy to monotherapy seems feasible in a majority
      of patients with schizophrenia. Assertive interventions, rather than passive
      educational approaches alone, appear more effective in reducing antipsychotic
      polypharmacy.

PMID- 23158206
TI  - Investigating a cluster of vulvar cancers in young women: distribution of human
      papillomavirus and HPV-16 variants in vulvar dysplastic or neoplastic biopsies.
AB  - BACKGROUND: A high incidence of vulvar cancer, and its precursor lesion, high
      grade vulvar intraepithelial neoplasia (VIN) has been identified in young
      Indigenous women living in the Arnhem Land region of the Northern Territory (NT)
      of Australia. This clustering is restricted to women aged <50 years, suggesting
      that oncogenic human papillomavirus (HPV) is a key causal factor. This study
      compared the HPV genotype prevalence, HPV-16 variant distribution and
      p16(INK4a)expression in stored vulvar cancer and high-grade VIN biopsy specimens
      from women residing in Arnhem Land, with specimens taken from Indigenous and non
      Indigenous women in other regions of NT where there is no observed increase in
      vulvar cancer incidence. METHODS: Twenty high-grade VIN and 10 invasive cancer
      biopsies were assessed from Arnhem Land along with 24 high-grade VIN and 10
      invasive cancer biopsies from other regions of NT. RESULTS: Biopsies from Arnhem
      Land were similar to those from other regions in the detection of high-risk (HR)
      or possible HR HPV (VIN: 95% and 84% respectively for Arnhem Land and other
      regions, P=0.356; invasive cancer: 100% and 80%, P=0.473), HPV-16 (VIN: 60% and
      80%, P=0.364; invasive cancer: 70% and 70%, P=1.0) and p16(INK4a) expression
      (VIN: 90% and 84%, P=0.673; invasive cancer: 100% and 80%, P=0.474). All HPV-16
      variants were of the European prototype. CONCLUSION: Comparison of biopsies
      revealed no significant difference in the frequency of oncogenic HPVs or HPV-16
      variant types between Arnhem Land and other regions, suggesting another cofactor
      in this cluster.

PMID- 23158208
TI  - Examining the reliability of the flexor carpi radialis V-wave at different levels
      of muscle contraction.
AB  - This study examined the reliability and scaling of the flexor carpi radialis
      (FCR) V-wave during submaximal and maximal voluntary muscle contractions (MVC).
      23 participants were tested on three separate sessions. For each session,
      participants performed isometric wrist flexions at five contraction levels (20,
      40, 60, 80 and 100 %MVC). When the target contraction level was reached, a
      supramaximal electrical stimulus was applied to the median nerve in order to
      elicit an FCR V-wave. Across all participants, the FCR V-wave amplitude,
      normalized to its superimposed M-wave amplitude, increased from 0.030+/-0.001 to
      0.143+/-0.015 (P<0.001) as the muscle contraction increased from 20 to 100 %MVC.
      Contraction level did not influence the reliability of evoking the FCR V-wave, as
      the V-wave demonstrated both stability and consistency. With the exception of a
      single day main effect during the 20 %MVC condition, V:Msup was not different
      across days or trials (P>0.05) indicating measurement stability. High reliability
      co-efficients (0.827-0.913) at each contraction level signified measurement
      consistency. This study establishes that FCR V-waves can be reliably evoked
      during both submaximal and maximal muscle contractions and suggests the
      possibility for FCR V-wave recordings to be used to document neuromuscular
      adaptations associated with factors such as training or fatigue.

PMID- 23158207
TI  - Predictors of adverse events after endovascular abdominal aortic aneurysm repair:
      A meta-analysis of case reports.
AB  - INTRODUCTION: Endovascular abdominal aortic aneurysm repair is a life-saving
      intervention. Nevertheless, complications have a major impact. We review the
      evidence from case reports for risk factors of complications after endovascular
      abdominal aortic aneurysm repair. CASE PRESENTATION: We selected case reports
      from PubMed reporting original data on adverse events after endovascular
      abdominal aortic aneurysm repair. Extracted risk factors were: age, sex, aneurysm
      diameter, comorbidities, re-interventions, at least one follow-up visit being
      missed or refusal of a re-intervention by the patient. Extracted outcomes were:
      death, rupture and (non-)device-related complications.In total 113 relevant
      articles were selected. These reported on 173 patients. A fatal outcome was
      reported in 15% (N = 26) of which 50% came after an aneurysm rupture (N = 13).
      Non-fatal aneurysm rupture occurred in 15% (N = 25). Endoleaks were reported in
      52% of the patients (N = 90). In half of the patients with a rupture no prior
      endoleak was discovered during follow-up. In 83% of the patients one or more re
      interventions were performed (N = 143). Mortality was higher among women (risk
      ratio 2.9; 95% confidence interval 1.4 to 6.0), while the presence of
      comorbidities was strongly associated with both ruptures (risk ratio 1.6; 95%
      confidence interval 0.9 to 2.9) and mortality (risk ratio 2.1; 95% confidence
      interval 1.0 to 4.7). Missing one or more follow-up visits (>=1) or refusal of a
      re-intervention by the patient was strongly related to both ruptures (risk ratio
      4.7; 95% confidence interval 3.1 to 7.0) and mortality (risk ratio 3.8; 95%
      confidence interval 1.7 to 8.3). CONCLUSION: Female gender, the presence of
      comorbidities and at least one follow-up visit being missed or refusal of a re
      intervention by the patient appear to increase the risk for mortality after
      endovascular abdominal aortic aneurysm repair. Larger aneurysm diameter, higher
      age and multimorbidity at the time of surgery appear to increase the risk for
      rupture and other complications after endovascular abdominal aortic aneurysm
      repair. These risk factors deserve further attention in future studies.

PMID- 23158209
TI  - Protein gene product 9.5 is diagnostically helpful in delineating high-grade
      renal cell cancer involving the renal medullary/sinus region from invasive
      urothelial cell carcinoma of the renal pelvis.
AB  - The classification of poorly differentiated carcinomas involving the renal
      medullary/sinus region might be challenging on conventional histomorphologic
      grounds alone. However, delineation of high-grade renal cell carcinomas such as
      collecting duct (Bellini) carcinoma from urothelial cell carcinoma of the renal
      pelvis is critical, as it conveys important therapeutic implications. We assessed
      the so far neglected differential diagnostic role of protein gene product 9.5, a
      neuropeptide involved in intracellular proteolysis, in terms of differentiating
      invasive urothelial cell carcinomas of the renal pelvis from high-grade renal
      cell carcinomas infiltrating the renal medullary/sinus region. To this aim, 21
      invasive urothelial cell carcinomas of the renal pelvis and 27 high-grade renal
      cell carcinomas (8 renal cell carcinomas with sarcomatoid dedifferentiation and 5
      type 1 and 7 type 2 papillary renal cell carcinomas as well as 7 collecting duct
      carcinomas) were stained with antibodies directed against protein gene product
      9.5, CD10, vimentin, CEA, p63, CK5/6, CK7, CK20, PAX2, PAX8, CD117 (c-Kit),
      AE1/3, alpha-methyl CoA racemase, actin, and desmin. Briefly, strong protein gene
      product 9.5 expression was observed in 6 (86%) of 7 collecting duct carcinomas, 8
      (67%) of 12 papillary renal cell carcinomas, and 2 (25%) of 8 renal cell
      carcinomas with sarcomatoid dedifferentiation. Conversely, none of the 21
      urothelial cell carcinomas investigated showed protein gene product 9.5
      expression. Our findings suggest that protein gene product 9.5, particularly if
      used in conjunction with p63 and CK5/6, might be helpful in differentiating high
      grade renal cell carcinomas from urothelial cell carcinomas of the renal pelvis,
      whereas its specificity with respect to the histologic subtyping of renal cell
      carcinomas seems to be low. However, because of the limited number of study cases
      enrolled in our investigation, our findings need to be validated in the future.

PMID- 23158210
TI  - Epidermal growth factor receptor, phosphatidylinositol-3-kinase catalytic
      subunit/PTEN, and KRAS/NRAS/BRAF in primary resected esophageal adenocarcinomas:
      loss of PTEN is associated with worse clinical outcome.
AB  - Alterations of the epidermal growth factor receptor (EGFR) can be observed in a
      significant subset of esophageal adenocarcinomas (EACs), and targeted therapy
      against EGFR may become an interesting approach for the treatment of these
      tumors. Mutations of KRAS, NRAS, BRAF, and phosphatidylinositol-3-kinase
      catalytic subunit (PIK3CA) and deregulation of PTEN expression influence the
      responsiveness against anti-EGFR therapy in colorectal carcinomas. We
      investigated the prevalence of these events in a collection of 117 primary
      resected EACs, correlated the findings with EGFR expression and amplification,
      and determined their clinicopathologic impact. KRAS mutations were detected in 4
      (3%) of 117 tumors (3* G12D and 1 G12V mutation). One tumor had a PIK3CA E545K
      mutation. Neither NRAS nor BRAF mutations were detected. Sixteen (14%) of 117
      cases were negative for PTEN expression, determined by immunohistochemistry. Loss
      of PTEN was observed predominantly in advanced tumor stages (P = .004). There was
      no association between PTEN and EGFR status. Loss of PTEN was associated with
      shorter overall and disease-free survival (P < .001 each) and also an independent
      prognostic factor in multivariate analysis (P = .015). EGFR status had no
      prognostic impact in this case collection. In summary, loss of PTEN can be
      detected in a significant subset of EAC and is associated with an aggressive
      phenotype. Therefore, PTEN may be useful as a prognostic biomarker. In contrast,
      mutations of RAS/RAF/PIK3CA appear only very rarely, if at all, in EAC. A
      possible predictive role of PTEN in anti-EGFR treatment warrants further
      investigations, whereas determination of RAS/RAF/PIK3CA mutations may only have a
      minor impact in this context.

PMID- 23158211
TI  - Diagnostic and prognostic role of steroidogenic factor 1 in adrenocortical
      carcinoma: a validation study focusing on clinical and pathologic correlates.
AB  - The pathologic characterization of adrenocortical cancer is still problematic for
      several reasons, including the identification of novel markers of diagnostic or
      prognostic relevance. Among them, steroidogenic factor 1 deserves major interest
      because of its potential usefulness as a marker of adrenocortical derivation and
      of biological aggressiveness. Our aim was to validate its prognostic relevance in
      a large series of adrenocortical cancer, comparing the performance of 2 different
      commercial antibodies and investigating its expression in adrenocortical cancer
      variants and in comparison with clinical and pathologic features. Seventy-five
      (including 53 classical, 10 myxoid, and 12 oncocytic) adrenocortical cancer cases
      were included in tissue microarrays and analyzed for the immunohistochemical
      expression of steroidogenic factor 1 using 2 commercial antibodies, 1 polyclonal
      and 1 monoclonal (N1665). Nuclear steroidogenic factor 1 staining was assessed
      using a semiquantitative score and correlated with adrenocortical cancer type and
      clinical pathologic characteristics. A weak but significant correlation was found
      comparing the 2 antibodies with a positive rate of 88% and 58% using the
      monoclonal and polyclonal antibodies, respectively. High steroidogenic factor 1
      expression with the N1665 antibody was positively correlated with high mitotic
      count, high Ki-67 index, and high European Network for the Study of Adrenal
      Tumors (ENSAT) stage and negatively associated with loss of functionality and
      presence of oncocytic features. Moreover, high steroidogenic factor 1 expression
      with this same antibody was significantly associated at univariate analysis with
      a decreased survival, together with high Ki-67 and mitotic indexes, with a trend
      to significance confirmed by multivariate analysis, thus supporting the detection
      of steroidogenic factor 1 using the N1665 antibody as a novel prognostic marker
      in adrenocortical cancer.

PMID- 23158212
TI  - The diagnostic use of ERG in resolving an "atypical glands suspicious for cancer"
      diagnosis in prostate biopsies beyond that provided by basal cell and alpha
      methylacyl-CoA-racemase markers.
AB  - Immunohistochemical (IHC) staining for ERG is used as a surrogate for TMPRSS2-ERG
      gene fusion, a specific molecular event seen in ~50% of prostate carcinomas
      (PCas) and ~20% of high-grade prostatic intraepithelial neoplasia (HGPIN)
      intermingled with adjacent PCa demonstrating identical gene fusions. We studied
      84 "atypical glands suspicious for cancer (ATYP)" cases using multiplex ERG/alpha
      methylacyl-CoA-racemase (AMACR)/high-molecular-weight cytokeratin/p63 IHC to
      determine how often ERG contributes to resolving an ATYP diagnosis beyond that
      provided by AMACR and basal markers. Final diagnoses of benign, ATYP, and cancer
      were rendered after review of morphology and all markers in 3, 30, and 51 cases,
      respectively. Of 51 cancer diagnoses, 45% and 94% were positive for ERG and
      AMACR, respectively. Of 30 atypical diagnoses, 10% and 67% were positive for ERG
      and AMACR, respectively. Of 3 benign diagnoses, none and 83% were positive for
      ERG and AMACR, respectively. Three ERG-positive atypical cases were classified as
      "HGPIN with adjacent ATYP." ERG was expressed in adjacent noncancer glands of 20%
      of PCas, whereas AMACR was expressed in noncancer glands in all diagnostic
      categories in 40% of cases. Positive ERG staining helped establish the initial
      ATYP diagnosis to PCa in 28% cases whose diagnoses would otherwise remain ATYP
      based on AMACR and basal markers. ERG positivity in small atypical glands where
      HGPIN diagnosis is excluded helps establish a definitive cancer diagnosis in a
      small proportion of additional ATYP cases. We recommend judicious use of ERG,
      preferably as a component of multiplex IHC, in evaluation of difficult prostate
      biopsies.

PMID- 23158214
TI  - Small-cell lung cancer presenting as hypopituitarism.

PMID- 23158213
TI  - Cryopreservation of aoudad (Ammotragus lervia sahariensis) sperm obtained by
      transrectal ultrasound-guided massage of the accessory sex glands and
      electroejaculation.
AB  - This study examines (1) the effectiveness of transrectal, ultrasound-guided
      massage of the accessory sex glands (TUMASG) combined with electroejaculation for
      obtaining aoudad (Ammotragus lervia sahariensis) sperm samples for
      cryopreservation, and (2) the effectiveness of a Tris-citric acid-glucose-based
      medium (TCG; usually used for freezing ibex sperm) and a TES-Tris-glucose-based
      medium (TTG; typically used in the cryopreservation of mouflon sperm) as sperm
      extenders. After TUMASG, just one to three electrical pulses were required for
      ejaculation to occur in five of the six animals studied; one ejaculated after
      TUMASG alone. Transrectal, ultrasound-guided massage of the accessory sex glands
      would therefore appear to be useful in obtaining sperm samples from this species,
      requiring few subsequent electrical electroejaculation stimuli and sometimes none
      at all. After thawing, the membrane integrity (assessed by nigrosin-eosin
      staining) of sperm extended with TTG was greater than that of sperm extended with
      TCG (P < 0.05). The total percentage of sperm showing an intact acrosome, as
      assessed by fluorescein isothiocyanate-conjugated peanut (Arachis hypogea)
      agglutinin, was also higher in the TTG-extended sperm (P < 0.05), and the
      percentage of dead sperm with a damaged acrosome was lower (P < 0.05). No
      differences were seen between TCG and TTG in terms of apoptotic manifestations
      (DNA damage, caspase activity, mitochondrial membrane potential, and plasmalemma
      stability). Therefore, TTG appears to be a better extender than TCG for
      cryopreserving aoudad sperm.

PMID- 23158215
TI  - Plasmonic enhancements of photoluminescence in hybrid Si nanostructures with Au
      fabricated by fully top-down lithography.
AB  - The authors study plasmonic enhancements of photoluminescence (PL) in Si
      nanodisk (ND) arrays hybridized with nanostructures such as nanoplates of Au,
      where these hybrid nanostructures are fabricated by fully top-down lithography:
      neutral-beam etching using bio-nano-templates and high-resolution electron-beam
      lithography. The separation distance between the Si ND and Au nanostructure
      surfaces is precisely controlled by inserting a thin SiO2 layer with a thickness
      of 3 nm. We observe that PL intensities in the Si NDs are enhanced by factors up
      to 5 depending on the wavelength by integrating with the Au nanoplates. These
      enhancements also depend on the size and shape of the Au nanoplates.

PMID- 23158216
TI  - A modified analysis for thermal-mechanical properties of staggered structure in
      biomimetic materials.
AB  - The thermal-mechanical stress distributions and equivalent coefficient of thermal
      expansion (CTE) of the staggered arrangement of mineral platelets wrapped by soft
      matrix are analyzed, which exist in numerous natural biological and biomimetic
      materials. Two analytical models, 'Stress model' and 'Displacement model', were
      established from the ways of stress and displacement solution based on the
      modification of classical shear-lag model. Complementary finite element analysis
      (FEA) was used to verify the analytical models. Results reveal that, compared to
      'Displacement model', 'Stress model' gives a better prediction of the stress
      distributions within the staggered structure referring to FEA. The equivalent CTE
      predicted by both models reach constant as the aspect ratio and volume fraction
      of platelets exceeding the critical values. Nevertheless, the relative error
      between the results from different models increases with the increase of the
      ratio of overlap to length of platelets. These provide a benchmark to the optimum
      design of micro/nano-structure in bio-inspired materials suffering to temperature
      fluctuation and applied loading.

PMID- 23158217
TI  - Micromechanical modeling of R-curve behaviors in human cortical bone.
AB  - The risk of bone fracture increases with age because of a variety of factors that
      include, among others, decreasing bone quantity and quality due to increasing
      porosity and crack density with age. Experimental evidence has indicated that
      changes in bone microstructure and trace mineralization with age can result in
      different crack-tip strain field and fracture response, leading to different
      fracture mechanisms and R-curve behaviors. In this paper, a micromechanical
      modeling approach is developed to predict the R-curve response of bone tissue by
      delineating fracture mechanisms that lead to microdamage and ligament bridging by
      incorporating the influence of increasing porosity and crack density with age.
      The effects of age on fracture of human femur cortical bone due to porosity (bone
      quantity) and bone quality (crack density) with age are then examined via the
      micromechanical model.

PMID- 23158218
TI  - Developmental associations between traits of autism spectrum disorder and
      attention deficit hyperactivity disorder: a genetically informative, longitudinal
      twin study.
AB  - BACKGROUND: Autism spectrum disorder (ASD) and attention deficit hyperactivity
      disorder (ADHD), and associated subclinical traits, regularly co-occur with one
      another. However, the aetiology of their co-occurrence remains poorly understood.
      This paper provides the first genetically informative, longitudinal analysis of
      the interaction between traits of ASD and ADHD, and explores their genetic and
      environmental overlap. METHOD: Parents of approximately 5000 twin pairs completed
      questionnaires assessing traits of ASD and ADHD when twins were aged 8 and 12
      years. Cross-lagged longitudinal modelling explored their developmental
      association, enabling a consideration of phenotypic-driven processes. Overlapping
      aetiological influences on traits at age 12 years were explored using bivariate
      twin modelling. RESULTS: Traits of ADHD at age 8 years were more strongly
      predictive of traits of ASD at 12 years than traits of ASD at 8 years were of
      traits of ADHD at 12 years. Analysis of traits by subscales assessing specific
      symptom domains suggested that communication difficulties were most strongly
      associated with traits of ADHD. Bivariate modelling suggested moderate genetic
      overlap on traits in males (genetic correlation = 0.41), and a modest degree of
      overlap in females (genetic correlation = 0.23) at age 12 years. CONCLUSIONS:
      Traits of ADHD at age 8 years significantly influence traits of ASD at age 12
      years, after controlling for their initial relationship at age 8 years. In
      particular, early ADHD traits influenced later communication difficulties. These
      findings demonstrate the dynamic nature of co-occurring traits across
      development. In addition, these findings add to a growing body of literature
      suggesting that traits of ASD and ADHD may arise via similar aetiological
      processes.

PMID- 23158219
TI  - Patterns and early evolution of organ failure in the intensive care unit and
      their relation to outcome.
AB  - INTRODUCTION: Recognition of patterns of organ failure may be useful in
      characterizing the clinical course of critically ill patients. We investigated
      the patterns of early changes in organ dysfunction/failure in intensive care unit
      (ICU) patients and their relation to outcome. METHODS: Using the database from a
      large prospective European study, we studied 2,933 patients who had stayed more
      than 48 hours in the ICU and described patterns of organ failure and their
      relation to outcome. Patients were divided into three groups: patients without
      sepsis, patients in whom sepsis was diagnosed within the first 48 hours after ICU
      admission, and patients in whom sepsis developed more than 48 hours after
      admission. Organ dysfunction was assessed by using the sequential organ failure
      assessment (SOFA) score. RESULTS: A total of 2,110 patients (72% of the study
      population) had organ failure at some point during their ICU stay. Patients who
      exhibited an improvement in organ function in the first 24 hours after admission
      to the ICU had lower ICU and hospital mortality rates compared with those who had
      unchanged or increased SOFA scores (12.4 and 18.4% versus 19.6 and 24.5%, P <
      0.05, pairwise). As expected, organ failure was more common in sepsis than in
      nonsepsis patients. In patients with single-organ failure, in-hospital mortality
      was greater in sepsis than in nonsepsis patients. However, in patients with
      multiorgan failure, mortality rates were similar regardless of the presence of
      sepsis. Irrespective of the presence of sepsis, delta SOFA scores over the first
      4 days in the ICU were higher in nonsurvivors than in survivors and decreased
      significantly over time in survivors. CONCLUSIONS: Early changes in organ
      function are strongly related to outcome. In patients with single-organ failure,
      in-hospital mortality was higher in sepsis than in nonsepsis patients. However,
      in multiorgan failure, mortality rates were not influenced by the presence of
      sepsis.

PMID- 23158220
TI  - Vision surveillance in the United States: has the time come?

PMID- 23158221
TI  - Surveillance of disparities in vision and eye health in the United States: an
      expert panel's opinions.
AB  - PURPOSE: To define surveillance approaches and metrics to capture the burden of
      vision health disparities and to identify properties of a surveillance system to
      guide public health interventions. DESIGN: Expert panel. METHODS: Analysis of
      relevant literature and deliberations of expert panel. RESULTS: The panel
      identified that the purpose of vision surveillance was to link data to public
      health interventions. Panel members noted the importance of assessing vision
      through self-reported and performance-based measures. Defined populations should
      be included in a surveillance system to assess disparities in utilization of eye
      care and vision loss. The panel suggested that ophthalmic/vision measures should
      be sustained in national surveys and suggested that a vision surveillance system
      should be forged among federal agencies. CONCLUSIONS: Employing the 6 outlined
      strategies would improve vision surveillance and help reach the vision-related
      objectives of Healthy People 2020.

PMID- 23158222
TI  - The variability of vision loss assessment in federally sponsored surveys: seeking
      conceptual clarity and comparability.
AB  - PURPOSE: To review U.S. national population-based surveys to evaluate
      comparability and conceptual clarity of vision measures. DESIGN: Perspective.
      METHODS: The vision questions in 12 surveys were mapped to the World Health
      Organization's International Classification of Functioning, Disability and Health
      framework under the domains of condition, impairment, activity limitation,
      participation, and environment. Surveys examined include the National Health
      Interview Survey, the Behavioral Risk Factor Surveillance Survey, National Health
      and Nutrition Examination Survey, the Census, and the Visual Function
      Questionnaire. RESULTS: Nearly 100 vision measures were identified in 12 surveys.
      These surveys provided no consistent measure of vision or vision impairment.
      Survey questions asked about differing characteristics of vision-related disease,
      function, and social roles. A question related to ability to read newspaper print
      was the most commonly asked question in surveys. CONCLUSIONS: Limited
      comparability of data and lack of conceptual clarity in the population-based
      surveys resulted in an inability to consistently characterize the population of
      people experiencing vision impairment. Consequently, vision surveillance was
      limited.

PMID- 23158223
TI  - Disparities in eye care utilization among the United States adults with visual
      impairment: findings from the behavioral risk factor surveillance system 2006
      2009.
AB  - PURPOSE: To estimate the prevalence of annual eye care among visually impaired
      United States residents aged 40 years or older, by state, race/ethnicity,
      education, and annual income. DESIGN: Cross-sectional study. METHODS: In analyses
      of 2006-2009 Behavioral Risk Factor Surveillance System data from 21 states, we
      used multivariate regression to estimate the state-level prevalence of yearly eye
      doctor visit in the study population by race/ethnicity (non-Hispanic white, non
      Hispanic black, Hispanic, and other), annual income (>=$35,000 and <$35,000), and
      education (< high school, high school, and > high school). RESULTS: The age
      adjusted state-level prevalence of yearly eye doctor visits ranged from 48%
      (Missouri) to 69% (Maryland). In Alabama, Colorado, Indiana, Iowa, New Mexico,
      and North Carolina, the prevalence was significantly higher among respondents
      with more than a high school education than among those with a high school
      education or less (P < .05). The prevalence was positively associated with annual
      income levels in Alabama, Georgia, New Mexico, New York, Texas, and West Virginia
      and negatively associated with annual income levels in Massachusetts. After
      controlling for age, sex, race/ethnicity, education, and income, we also found
      significant disparities in the prevalence of yearly eye doctor visits among
      states. CONCLUSION: Among visually impaired US residents aged 40 or older, the
      prevalence of yearly eye examinations varied significantly by race/ethnicity,
      income, and education, both overall and within states. Continued and possibly
      enhanced collection of eye care utilization data, such as we analyzed here, may
      help states address disparities in vision health and identify population groups
      most in need of intervention programs.

PMID- 23158226
TI  - Current concepts in decision-making research from bench to bedside.

PMID- 23158224
TI  - Vision health disparities in the United States by race/ethnicity, education, and
      economic status: findings from two nationally representative surveys.
AB  - PURPOSE: To assess vision health disparities in the United States by
      race/ethnicity, education, and economic status. DESIGN: Cross-sectional,
      nationally representative samples. METHODS: We used national survey data from the
      National Health and Nutrition Examination Survey (NHANES) and the National Health
      Interview Survey (NHIS). Main outcome measures included, from NHANES, age-related
      eye diseases (ie, age-related macular degeneration [AMD], cataract, diabetic
      retinopathy [DR], glaucoma) and from NHIS, eye care use (ie, eye doctor visits
      and cannot afford eyeglasses when needed) among those with self-reported visual
      impairment. The estimates were age- and sex-standardized to the 2000 US Census
      population. Linear trends in the estimates were assessed by weighted least
      squares regression. RESULTS: Non-Hispanic whites had a higher prevalence of AMD
      and cataract surgery than non-Hispanic blacks, but a lower prevalence of DR and
      glaucoma (all P < .001 in NHANES 2005-2008). From 1999 to 2008, individuals with
      less education (ie, <high school vs >high school) and lower income (poverty
      income ratio [PIR] <1.00 vs >= 4.00) were consistently less likely to have had an
      eye care visit in the past 12 months compared with their counterparts (all P <
      .05). During this period, inability to afford needed eyeglasses increased among
      non-Hispanic whites and Hispanics (trend P = .004 and P = .007; respectively),
      those with high school education (trend P = .036), and those with PIR 1.00-1.99
      (trend P < .001). CONCLUSIONS: Observed vision health disparities suggest a need
      for educational and innovative interventions among socioeconomically
      disadvantaged groups.

PMID- 23158225
TI  - Use of electronic health records and administrative data for public health
      surveillance of eye health and vision-related conditions in the United States.
AB  - PURPOSE: To discuss the current trend toward greater use of electronic health
      records and how these records could enhance public health surveillance of eye
      health and vision-related conditions. DESIGN: Perspective, comparing systems.
      METHODS: We describe 3 currently available sources of electronic health data
      (Kaiser Permanente, the Veterans Health Administration, and the Centers for
      Medicare & Medicaid Services) and how these sources can contribute to a
      comprehensive vision and eye health surveillance system. RESULTS: Each of the 3
      sources of electronic health data can contribute meaningfully to a comprehensive
      vision and eye health surveillance system, but none currently provide all the
      information required. The use of electronic health records for vision and eye
      health surveillance has both advantages and disadvantages. CONCLUSIONS:
      Electronic health records may provide additional information needed to create a
      comprehensive vision and eye health surveillance system. Recommendations for
      incorporating electronic health records into such a system are presented.

PMID- 23158227
TI  - Sensitivity to fairness and intentions of others in the ultimatum game in
      patients with ventromedial prefontal lesions.
AB  - This study aimed to examine the relationship between perspective-taking and
      impaired decision-making in patients with ventromedial prefrontal (VM) lesions,
      using the Ultimatum Game (UG). In the UG, two players split a sum of money and
      one player proposes a division while the other can accept or reject this. Eight
      patients with VM damage and 18 healthy controls participated as responders in a
      modified version of the UG, in which identical offers can generate different
      rejection rates depending on the other offers available to the proposer.
      Participants had to either accept or reject offers of 2:8 NIS (2NIS for them and
      8 NIS for the proposer), which were paired with one of four different possible
      offers (5:5, 4:6, 2:8, 8:2). Results indicate that the controls more often
      rejected offers of 2:8 when the alternative was 4:6 (a greedy alternative) than
      when the alternative was 5:5 (fair alternative), whereas the VM patients showed
      the opposite pattern of decision-making. Additionally, the overall rejection
      rates were higher in patients as compared to controls. Furthermore, scores on a
      perspective-taking scale were negatively correlated with rejection rates in the
      patient group, suggesting that perspective-taking deficits may account for
      impaired decision-making in VM patients.

PMID- 23158228
TI  - Social Cognition and Emotional Assessment (SEA) is a marker of medial and orbital
      frontal functions: a voxel-based morphometry study in behavioral variant of
      frontotemporal degeneration.
AB  - The aim of this study was to explore the cerebral correlates of functional
      deficits that occur in behavioral variant frontotemporal dementia (bvFTD). A
      specific neuropsychological battery, the Social cognition & Emotional Assessment
      (SEA; Funkiewiez et al., 2012), was used to assess impaired social and emotional
      functions in 20 bvFTD patients who also underwent structural MRI scanning. The
      SEA subscores of theory of mind, reversal-learning tests, facial emotion
      identification, and apathy evaluation were entered as covariates in a voxel-based
      morphometry analysis. The results revealed that the gray matter volume in the
      rostral part of the medial prefrontal cortex [mPFC, Brodmann area (BA) 10] was
      associated with scores on the theory of mind subtest, while gray matter volume
      within the orbitofrontal (OFC) and ventral mPFC (BA 11 and 47) was related to the
      scores observed in the reversal-learning subtest. Gray matter volume within BA 9
      in the mPFC was correlated with scores on the emotion recognition subtest, and
      the severity of apathetic symptoms in the Apathy scale covaried with gray matter
      volume in the lateral PFC (BA 44/45). Among these regions, the mPFC and OFC
      cortices have been shown to be atrophied in the early stages of bvFTD. In
      addition, SEA and its abbreviated version (mini-SEA) have been demonstrated to be
      sensitive to early impairments in bvFTD (Bertoux et al., 2012). Taken together,
      these results suggest a differential involvement of orbital and medial prefrontal
      subregions in SEA subscores and support the use of the SEA to evaluate the
      integrity of these regions in the early stages of bvFTD.

PMID- 23158230
TI  - Expert versus proxy rating of verbal communicative ability of people with aphasia
      after stroke.
AB  - In randomized clinical trials of aphasia treatment, a functional outcome measure
      like the Amsterdam-Nijmegen Everyday Language Test (ANELT), administered by
      speech-language therapists, is often used. However, the agreement between this
      expert rating and the judgment of the proxy about the quality of the daily life
      communication of the person with aphasia is largely unknown. We examined the
      association between ANELT scores by speech-language therapists and proxy
      judgments on the Partner Communication Questionnaire both at 3 and 6 months in 39
      people with aphasia after stroke. We also determined which factors affected the
      level of agreement between expert and proxy judgment of the communicative ability
      at 6 months in 53 people with aphasia. We found moderate agreement (at 3 months r
      = .662; p = < .0001 and at 6 months r = .565; p = .0001), with proxies rating
      slightly higher than experts. Less severe aphasia, measured with the Aphasia
      Severity Rating Scale, was associated with better agreement. In conclusion,
      although proxies were slightly more positive than experts, we found moderate
      agreement between expert and proxy rating of verbal communicative ability of
      people with aphasia after stroke, especially in milder cases.

PMID- 23158229
TI  - Effects of maternal worm infections and anthelminthic treatment during pregnancy
      on infant motor and neurocognitive functioning.
AB  - We tested the hypothesis that maternal worm infections in pregnancy affect infant
      motor and neurocognitive development, and that anthelminthic treatment during
      pregnancy can reverse these effects. We used measures which examine infant motor,
      cognitive and executive function, including inhibition. We assessed 983 Ugandan
      infants aged 15 months, using locally appropriate measures within the Entebbe
      Mother and Baby Study, a trial of anthelminthic treatment during pregnancy. Key
      exposures were maternal worm infections and anthelminthic treatment during
      pregnancy. Effects of other health and social factors were controlled for
      statistically. Of the five major worm species found in the pregnant women, two
      had influences on the developmental measures: Maternal Mansonella perstans and
      Strongyloides stercoralis infections showed negative associations with the A-not
      B-task, and Language, respectively. Performance on other psychomotor and
      cognitive measures was associated with illnesses during infancy and infants'
      behavior during assessment, but not with maternal worm infections. There were no
      positive effects of maternal anthelminthic treatment on infant abilities.
      Mansonella perstans and Strongyloides stercoralis infection during pregnancy seem
      associated with impaired early executive function and language, respectively, but
      single-dose anthelminthic treatment during pregnancy was not beneficial. The
      biological mechanisms that could underlie these neurocognitive effects are
      discussed.

PMID- 23158231
TI  - Superior memory and higher cortical volumes in unusually successful cognitive
      aging.
AB  - It is "normal" for old age to be associated with gradual decline in memory and
      brain mass. However, there are anecdotal reports of individuals who seem immune
      to age-related memory impairment, but these individuals have not been studied
      systematically. This study sought to establish that such cognitive SuperAgers
      exist and to determine if they were also resistant to age-related loss of
      cortical brain volume. SuperAgers were defined as individuals over age 80 with
      episodic memory performance at least as good as normative values for 50- to 65
      year-olds. Cortical morphometry of the SuperAgers was compared to two cognitively
      normal cohorts: age-matched elderly and 50- to 65-year-olds. The SuperAgers'
      cerebral cortex was significantly thicker than their healthy age-matched peers
      and displayed no atrophy compared to the 50- to 65-year-old healthy group.
      Unexpectedly, a region of left anterior cingulate cortex was significantly
      thicker in the SuperAgers than in both elderly and middle-aged controls. Our
      findings identify cognitive and neuroanatomical features of a cohort that appears
      to resist average age-related changes of memory capacity and cortical volume. A
      better understanding of the underlying factors promoting this potential
      trajectory of unusually successful aging may provide insight for preventing age
      related cognitive impairments or the more severe changes associated with
      Alzheimer's disease.

PMID- 23158232
TI  - Neuropsychological features of asymptomatic c.709-1G>A progranulin mutation
      carriers.
AB  - Mutations in the progranulin (PGRN) gene have been identified as a cause of
      frontotemporal dementia (FTD). However, little is known about the
      neuropsychological abilities of asymptomatic carriers of these mutations. The aim
      of the study was to assess cognitive functioning in asymptomatic c.709-1G>A PGRN
      mutation carriers. We hypothesized that poorer neuropsychological performance
      could be present before the development of clinically significant FTD symptoms.
      Thirty-two asymptomatic first-degree relatives of FTD patients carrying the c.709
      1G>A mutation served as study participants, including 13 PGRN mutation carriers
      (A-PGRN+) and 19 non-carriers (PGRN-). A neuropsychological battery was
      administered. We found that the A-PGRN+ participants obtained significantly
      poorer scores than PGRN- individuals on tests of attention (Trail-Making Test
      Part A), mental flexibility (Trail-Making Test Part B), and language (Boston
      Naming Test). Poorer performance on these tests in asymptomatic PGRN mutation
      carriers may reflect a prodromal phase preceding the onset of clinically
      significant symptoms of FTD.

PMID- 23158233
TI  - The predictive validity of expressed emotions (EE) in schizophrenia. A 20-year
      prospective study.
AB  - BACKGROUND: The level of expressed emotions in the family (EE) and components
      thereof (emotional over-involvement EOI, and critical comments CC) have been
      found to be related to treatment outcomes in psychotic patients. One point of
      interest is the dynamic of various outcomes in relation to initial EE, CC and EOI
      levels. METHOD: 43 individuals with diagnosis of schizophrenia were assessed at
      1, 3, 7, 12 and 20-year follow-ups. The EE indicator was evaluated during the
      index hospitalization. Outcome indicators included: number of relapses, number
      and duration of in-patient rehospitalizations, and severity of psychopathological
      symptoms. RESULTS: 1) A high EE indicator was associated with a higher number of
      relapses in every follow-up and differences between the groups with low and high
      EE indicators proved significant after 3, 7, 12 and 20 years of the illness. 2) A
      high EE indicator was associated with a higher number of rehospitalizations after
      3 and 7 years, and showed as a clear trend after 12 and 20 years. 3) A high level
      of CC was associated with a higher number of relapses. 4) The severity of
      positive symptoms increased only in the group with high CC. 5) The negative
      syndrome was not associated with EE, EOI or CC. CONCLUSIONS: The EE indicator may
      be considered a valid prolonged predictor of relapses and rehospitalizations. A
      high level of CC was associated with a higher number of relapses and
      intensification of the positive syndrome in both the short-term and long-term
      course of the illness.

PMID- 23158234
TI  - A timely arrival for Born Too Soon.

PMID- 23158235
TI  - The misrepresentation of palliative care in the UK.

PMID- 23158236
TI  - Mental health in China: challenges and progress.

PMID- 23158240
TI  - Fred Sai: the godfather of family planning.

PMID- 23158241
TI  - CT scans in childhood and risk of leukaemia and brain tumours.

PMID- 23158242
TI  - CT scans in childhood and risk of leukaemia and brain tumours.

PMID- 23158243
TI  - CT scans in childhood and risk of leukaemia and brain tumours.

PMID- 23158245
TI  - CT scans in childhood and risk of leukaemia and brain tumours.

PMID- 23158246
TI  - CT scans in childhood and risk of leukaemia and brain tumours.

PMID- 23158247
TI  - Technologies for global health.

PMID- 23158248
TI  - Technologies for global health.

PMID- 23158249
TI  - Technologies for global health.

PMID- 23158251
TI  - Days of giants: remembering Albert Schweitzer.

PMID- 23158252
TI  - Seniors will not bankrupt Canada's health system.

PMID- 23158253
TI  - Acute severe visual loss and a brainstem mass.

PMID- 23158254
TI  - Intramucosal esophageal adenocarcinoma: primum non nocere.
AB  - OBJECTIVES: Intramucosal esophageal cancer treatment is evolving. Less-invasive
      therapies have emerged, necessitating review of safety, effectiveness, and
      determinants of long-term outcome after esophagectomy to clarify the role of this
      traditional, maximally invasive, and potentially harmful therapy. METHODS: From
      January 1983 to January 2011, 164 patients underwent esophagectomy alone for
      intramucosal adenocarcinoma. Cancers were subdivided by depth of invasion: lamina
      propria 50 (30%) and muscularis mucosa 114 (70%; inner 42 [26%], middle 16 [10%],
      and outer 56 [34%]). We assessed complications and esophagectomy-related
      mortality (safety) and cancer recurrence (effectiveness), and identified
      determinants of long-term outcomes. RESULTS: Barrett esophagus (P = .005), larger
      cancers (P < .001), worse histologic grade (P < .001), lymphovascular invasion (P
      < .001), and overstaging (P = .02) were associated with deeper cancers. One
      patient had regional lymph node metastases (0.6%). Seventy-five patients (46%)
      had complications. Seven of 9 deaths within 6 months were esophagectomy related,
      6 from respiratory failure. Seven patients had recurrence, all within 4 years.
      Five-, 10-, and 15-year survivals were 82%, 69%, and 60%, respectively, which
      were similar to those of a matched general population. Determinants of late
      mortality were older age (P = .004), poorer lung function (P < .0001), longer
      cancer (P = .04), postoperative pneumonia (P = .06), cancer recurrence (P <
      .0001), and second cancers (P < .0001). CONCLUSIONS: Survival after esophagectomy
      for intramucosal adenocarcinoma is excellent, determined more by patient than
      cancer characteristics. Patient selection and respiratory function are crucial to
      minimize harm. Considering the outcome of emerging therapies, esophagectomy
      should be reserved for patients with a long intramucosal adenocarcinoma or those
      in whom endoscopic therapies fail or are inappropriate.

PMID- 23158255
TI  - The fate of the neoaortic valve and root after the modified Ross-Konno procedure.
AB  - OBJECTIVES: In children with aortic valve disease associated with annular
      hypoplasia or complex multilevel left ventricular outflow tract obstruction, the
      Ross procedure, combined with a modified Konno-type aortoventriculoplasty, is
      advocated. We aim to examine the fate of the neoaortic apparatus and assess
      neoaortic valve function after the modified Ross-Konno procedure. METHODS: Forty
      three patients, with a median age of 6 years, underwent the modified Ross-Konno
      procedure with a myectomy but without the use of a ventricular septal patch.
      Serial postoperative echocardiograms (n = 187) were analyzed, and regression
      models adjusted for repeated measures were used to model the longitudinal growth
      of the neoaortic annulus and root. RESULTS: There were 2 operative deaths (5%)
      and 1 late mortality. At 8 years, survival was 93% and freedom from autograft,
      homograft, and all-cause reoperation was 100%, 81%, and 72%, respectively. The
      median postprocedure diameter and z score were 14 mm (7-21 mm) and +1.3 (-3.0 to
      +6.1) for the neoaortic annulus and 21 mm (9-30 mm) and +1.6 (-1.3 to +4.1) for
      the neoaortic root, respectively. Serial echocardiograms showed a progressive
      increase in annular (+0.56 mm/year, P < .001) and root (+0.89 mm/year, P < .001)
      diameters but little change in annular (-0.07/year, P = .08) and root (
      0.002/year, P = .96) z scores. Autograft regurgitation developed in 9 patients;
      however, the degree and progression of regurgitation over time were not
      significant (P = .22). CONCLUSIONS: After the modified Ross-Konno procedure, the
      neoaortic annulus and root increased in size proportionately to somatic growth.
      Autograft regurgitation, usually mild and stable, developed in few patients, and
      none required autograft reoperation. Our findings support the use of the modified
      Ross-Konno as the procedure of choice in children with aortic valve disease and
      complex left ventricular outflow tract obstruction.

PMID- 23158256
TI  - Tricuspid valve repair improves early right ventricular and tricuspid valve
      remodeling in patients with hypoplastic left heart syndrome.
AB  - OBJECTIVE: Tricuspid regurgitation is a significant risk factor for reoperation
      and mortality in patients with hypoplastic left heart syndrome. The effects of
      tricuspid valve repair on quantitative measures of right ventricle and tricuspid
      valve remodeling have not been well documented. METHODS: We reviewed
      retrospectively the 2-dimensional echocardiograms of 17 tricuspid valve repairs
      (male, n = 12; female, n = 5; median age, 30 months; age range, 1.5-53 months)
      performed 1 month before and after tricuspid valve repair between 2005 and 2011.
      From the apical 4-chamber view, we measured right ventricle end-diastolic area,
      right ventricle fractional area change, and tricuspid valve leaflet coaptation
      length. The severity of tricuspid regurgitation was graded qualitatively. A 2
      sided paired t test was used to compare changes in tricuspid valve and right
      ventricle outcomes, and the Wilcoxon signed-rank test was used to compare changes
      in tricuspid regurgitation grades. RESULTS: Right ventricle end-diastolic area
      decreased significantly after tricuspid valve repair from 14.1 +/- 5.2 to 11.8 +/
      3.9 cm(2) (P = .001), whereas right ventricle fractional area change declined
      from 44.4% +/- 6.4% to 39.7% +/- 8.5% (P = .016). The coaptation length of the
      lateral and septal leaflet improved significantly after tricuspid valve repair
      (0.4 +/- 2.4 mm vs 3.1 +/- 2.7 mm, P = .002; 2.0 +/- 2.7 vs 3.4 +/- 2.0 mm, P =
      .036; respectively). Furthermore, the tricuspid regurgitation grade improved
      after tricuspid valve repair (3.1 +/- 0.6 to 1.7 +/- 0.9, P < .001). CONCLUSIONS:
      Tricuspid valve repair improved significantly the tricuspid valve coaptation
      length and reduced right ventricle volume in children with hypoplastic left heart
      syndrome. Further follow-up of decreased right ventricle function is required to
      determine whether this is a temporary phenomenon related to reduced right
      ventricle preload, permanent right ventricle dysfunction from late repair of the
      tricuspid valve, or unavoidable sequelae of a right ventricle exposed to systemic
      vascular resistance.

PMID- 23158257
TI  - Long-term follow-up after aortic valve replacement with Edwards Prima Plus
      stentless bioprostheses in patients younger than 60 years of age.
AB  - OBJECTIVES: The Edwards Prima Plus was one of the first stentless aortic valve
      bioprostheses, with larger orifice areas and improved hemodynamics compared to
      stented bioprostheses. The aim of the present single-center retrospective study
      was to assess the long-term results of the Edwards Prima Plus in patients 60
      years old or younger. METHODS: From 1993 to 2001, 120 patients (99 men and 21
      women) aged 60 years or younger underwent implantation of the Edwards Prima Plus.
      The indications were stenosis and/or insufficiency. Associated procedures were
      performed in 38 patients (31.7%). Of the patients, 39% had impaired left
      ventricular function. Follow-up data were acquired by telephone interview. Time
      to event analyses were performed using the Kaplan-Meier method. Variables
      affecting survival and freedom from reoperation were evaluated using Cox
      regression analysis. The mean patient age at surgery was 53.1 +/- 8.0 years. The
      follow-up data were 88.8% complete at a mean of 8.5 +/- 4.5 years. The total
      follow-up was 1022.7 patient-years. RESULTS: At 10 and 15 years, the overall
      actuarial survival rate was 71.8% +/- 4.4% and 48.8% +/- 9.6%, respectively.
      Survival was significantly lower for patients with older age, aortic
      insufficiency as the surgical indication, and small prosthesis size (<=25 mm vs
      >=27 mm). Reoperation was performed in 20 patients (16.7%), with a hospital
      mortality of 5%. At 10 and 14 years, the overall freedom from reoperation rate
      was 85.6% +/- 3.7% and 65.2% +/- 8.6%, respectively. Freedom from reoperation was
      significantly lower in patients with a small prosthesis size (<=25 mm) and
      insufficiency as the indication for surgery. CONCLUSIONS: In patients aged 60
      years or younger, an Edwards Prima Plus can provide reliable long-term results
      with acceptable freedom-from-reoperation rates.

PMID- 23158259
TI  - Determinants of patient satisfaction regarding pain care.
AB  - BACKGROUND: The management of pain in hospitalized patients remains a major
      public hospital priority. It has been the object of three French national
      programs since 1999. The purpose of this study was to reassess pain prevalence,
      pain intensity and patient perception of its management ten years after the first
      national program and to determine the factors related to the patient satisfaction
      with efforts to decrease pain intensity. METHODS: A 1-day cross-sectional survey
      in a university hospital. RESULTS: Pain prevalence was 59%. Pain intensity varied
      according to the medical department with lower intensity in surgery and
      obstetrics than medicine departments. Eighty-one percent of patients were
      satisfied with their pain management. Patient satisfaction was higher when
      doctors and nurses were heavily involved in the process of pain relief (OR=6.6;
      95% CI 3.8, 11.4), and when their pain had decreased (OR=2.9; 1.7, 5.0). The
      magnitude of decrease in pain were higher when the medical team was involved
      (OR=1.9; 95% IC 1.1, 3.3) and pain intensity was measured (OR=1.6; 1.0, 2.4).
      Perceptions of doctor and nurse involvement in the patient's care was higher when
      pain intensity was measured (OR=6.0; 3.4, 10.5), an immediate treatment offered
      (OR=3.5; 2.0, 6.2), encouragement to ask for an analgesic was provided (OR=2.0;
      1.1, 3.5) and for patients with acute pain (OR=2.2; 1.0, 4.7). CONCLUSIONS: This
      study identifies the factors related to patient satisfaction with pain management
      and the magnitude of the decrease in pain which should allow further efforts to
      improve the management of pain and reduce its intensity in hospital inpatients.

PMID- 23158260
TI  - Measuring financial protection for health in families with chronic conditions in
      Rural China.
AB  - BACKGROUND: As the world's largest developing country, China has entered into the
      epidemiological phase characterized by high life expectancy and high morbidity
      and mortality from chronic diseases. Cardiovascular diseases, chronic obstructive
      pulmonary diseases, and malignant tumors have become the leading causes of death
      since the 1990s. Constant payments for maintaining the health status of a family
      member who has chronic diseases could exhaust household resources, undermining
      fiscal support for other necessities and eventually resulting in poverty. The
      purpose of this study is to probe to what degree health expenditure for chronic
      diseases can impoverish rural families and whether the New Cooperative Medical
      Scheme can effectively protect families with chronic patients against
      catastrophic health expenditures. METHODS: We used data from the 4th National
      Health Services Survey conducted in July 2008 in China. The rural sample we
      included in the analysis comprised 39,054 households. We used both households
      suffering from medical impoverishment and households with catastrophic health
      expenditures to compare the financial protection for families having a chronic
      patient with different insurance coverage statuses. We used a logistic regression
      model to estimate the impact of different benefit packages on health financial
      protection for families having a chronic patient. RESULTS: An additional 10.53%
      of the families with a chronic patient were impoverished because of healthcare
      expenditure, which is more than twice the proportion in families without a
      chronic patient. There is a higher catastrophic health expenditure incidence in
      the families with a chronic patient. The results of logistic regression show that
      simply adding extra benefits did not reduce the financial risks. CONCLUSIONS:
      There is a lack of effective financial protection for healthcare expenditures for
      families with a chronic patient in rural China, even though there is a high
      coverage rate with the New Cooperative Medical Schemes. Given the coming
      universal coverage by the New Cooperative Medical Scheme and the increasing
      central government funds in the risk pool, effective financial protection for
      families should be possible through systematic reform of both financing
      mechanisms and payment methods.

PMID- 23158261
TI  - Individual and community level socioeconomic inequalities in contraceptive use in
      10 Newly Independent States: a multilevel cross-sectional analysis.
AB  - INTRODUCTION: Little is known regarding the association between socioeconomic
      factors and contraceptive use in the Newly Independent States (NIS), countries
      that have experienced profound changes in reproductive health services during the
      transition from socialism to a market economy. METHODS: Using 2005-2006 data from
      Demographic Health Surveys (Armenia, Azerbaijan, and Moldova) and Multiple
      Indicator Cluster Surveys (Belarus, Georgia, Kazakhstan, Kyrgyzstan, Tajikistan,
      Ukraine, and Uzbekistan), we examined associations between individual and
      community socioeconomic status with current modern contraceptive use (MCU) among
      N = 55,204 women aged 15-49 married or in a union. Individual socioeconomic
      status was measured using quintiles of wealth index and education level (higher
      than secondary school, secondary school or less). Community socioeconomic status
      was measured as the percentage of households in the poorest quintile of the
      nationals household wealth index (0%, 0-25%, or greater than 25%). We used
      multilevel logistic regression to estimate associations adjusted for age, number
      of children, urban/rural, and socioeconomic variables. RESULTS: MCU varied by
      country from 14% (in Azerbaijan) to 62% (in Belarus). Overall, women living in
      the poorest communities were less likely than those in the richest to use modern
      contraceptives (adjusted odds ratio (aOR) = 0.82, 95% Confidence Interval = 0.76,
      0.89). Similarly, there was an increasing odds of MCU with increasing individual
      level wealth. Women with a lower level of education also had lower odds of MCU
      than those with a higher level of education (aOR = .75, 95%CI = 0.71, 0.79). In
      country-specific analyses, community-level socioeconomic inequalities were
      apparent in 4 of 10 countries; in contrast, inequalities by individual-level
      wealth were apparent in 7 countries and by education in 8 countries. All
      countries in which community-level socioeconomic status was associated with MCU
      were in Central Asia, whereas at the individual-level inequalities of the largest
      magnitude were found in the Caucasus. There were no distinct patterns found in
      Eastern European countries. CONCLUSIONS: Community-level socioeconomic
      inequalities in MCU were most pronounced in Central Asian countries, whereas
      individual-level socioeconomic inequalities in MCU were most pronounced in the
      Caucasus. It is important to consider multilevel contextual determinants of
      modern contraceptive use in the development of reproductive health and family
      planning programs.

PMID- 23158262
TI  - Dynamic sentinel lymph node biopsy as the new paradigm for the management of
      penile cancer.
AB  - OBJECTIVES: The management of patients with penile cancer who have high-risk
      features for micrometastasis with clinically negative inguinal lymph nodes is
      controversial. We describe the history of the sentinel lymph node biopsy and how
      it has evolved to become a useful adjunct in the management of penile cancer.
      MATERIALS AND METHODS: Using a PubMed search, we identified the evidence relating
      to the management of the inguinal lymph nodes in penile cancer between 1977 and
      2010. RESULTS: The concept of the sentinel lymph node (SLN) was first described
      in 1977 for penile carcinoma where lymphangiograms were performed via the dorsal
      lymphatics of the penis to locate the primary lymphatic drainage zone of the
      penis situated near the saphenofemoral junction. Then, in 1992, the lymphatic
      mapping concept was further advanced by performing intradermal injections of blue
      dye to directly visualize the lymphatic channels and SLN in the treatment of
      melanoma. In 1994, investigators from The Netherlands pioneered the use of
      dynamic sentinel lymph node biopsies (DSLNB) for penile cancer by combining the
      use of peri-lesional blue dye injection, lymphoscintigraphy, and other future
      modifications of the technique to achieve low false negative biopsy rates (4.8%)
      as well as much lower morbidity (5.7%), compared with the 30%-50% morbidity
      associated with a full inguinal node dissection. CONCLUSION: DSLNB significantly
      decreases the morbidity associated with performing a standard or even modified
      inguinal lymph node dissection in patients with clinically negative inguinal
      lymph nodes. Performing DSLNB requires a multidisciplinary team of urologists,
      nuclear medicine radiologists, and pathologists working in cohesion to attain the
      best SLN detection rates with the lowest possible false-negative rates.

PMID- 23158263
TI  - Long-term trends in the epidemiology of human enteropathogens in Malaysia.

PMID- 23158264
TI  - Emergence of Klebsiella pneumoniae-producing KPC-2 carbapenemase in Paraiba,
      Northeastern Brazil.
AB  - The emergence of KPC-2 producing K. pneumoniae in hospitalized patients at the
      intensive care unit (ICU) of a teaching hospital located in the city of Joao
      Pessoa, Paraiba, Brazil, is reported. Seven carbapenem-resistant K. pneumoniae
      recovered from different body sites of infection were analyzed. Most isolates
      showed a multidrug-resistance phenotype. Genotypic analysis demonstrated the
      presence of two genotypes, with the predominance of genotype A, which belongs to
      ST 437. These isolates also carry the encoding genes of five other beta
      lactamases.

PMID- 23158265
TI  - Profile of patients diagnosed with AIDS at age 60 and above in Brazil, from 1980
      until June 2009, compared to those diagnosed at age 18 to 59.
AB  - OBJECTIVES: The aim of this study was to learn more about people diagnosed with
      acquired immunodeficiency syndrome (AIDS) at age 60 and above in Brazil, and to
      compare them with people diagnosed at a younger age. METHODS: This study was
      based on the analysis of secondary data from the Brazilian AIDS Program. The
      study population consisted of people diagnosed with AIDS at age 60 and above. The
      comparison group was comprised of a 20% random sample of people diagnosed at age
      18 to 59, frequency-matched by year of diagnosis. RESULTS: 544,846 cases of AIDS
      were reported in Brazil from 1980 until June 2009. Over 90% of cases were
      diagnosed between 18 and 59 years of age, and 13,657 (2.5%) at age 60 and above.
      The first case of AIDS among the elderly was reported in 1984. The comparison
      group consisted of 101,528 patients. Gender proportion was similar for both
      groups, and the proportion of people identified with AIDS after death in the
      Brazilian Mortality Information System (SIM) was 4% higher among the elderly.
      Both groups were also similar regarding the region of residence; a markedly
      higher proportion lived in Southeastern Brazil. Older people were more likely to
      have lower education and to have contracted AIDS by heterosexual contact, and
      less likely to be intravenous drug users. Male to female ratio among those
      diagnosed with AIDS at or above age 60 decreased over the years, in the same way
      as observed for the whole cohort. Mortality was higher among men in both groups.
      CD4 category (taken closest to the date of AIDS diagnosis) was very similar in
      both groups. CONCLUSION: The characteristics of the epidemic among the elderly
      show similarities to the younger group considering gender distribution and CD4
      category, but differ regarding educational level and exposure category. Also, the
      elderly were more likely not to have their AIDS condition promptly diagnosed.

PMID- 23158266
TI  - Healthcare-associated Staphylococcus aureus bloodstream infection: length of
      stay, attributable mortality, and additional direct costs.
AB  - This study aimed to determine the excess length of stay, extra expenditures, and
      attributable mortality to healthcare-associated S. aureus bloodstream infection
      (BSI) at a teaching hospital in central Brazil. The study design was a matched
      (1:1) case-control. Cases were defined as patients >13 years old, with a
      healthcare-associated S. aureus BSI. Controls included patients without an S.
      aureus BSI, who were matched to cases by gender, age (+/- 7 years), morbidity,
      and underlying disease. Data were collected from medical records and from the
      Brazilian National Hospital Information System (Sistema de Informacoes
      Hospitalares do Sistema Unico de Saude - SIH/SUS). A Wilcoxon rank sum test was
      performed to compare length of stay and costs between cases and controls.
      Differences in mortality between cases and controls were compared using McNemar's
      tests. The Mantel-Haenzel stratified analysis was performed to compare invasive
      device utilization. Data analyses were conducted using Epi Info 6.0 and
      Statistical Package for Social Sciences (SPSS 13.0). 84 case-control pairs
      matched by gender, age, admission period, morbidity, and underlying disease were
      analyzed. The mean lengths of hospital stay were 48.3 and 16.2 days for cases and
      controls, respectively (p<0.01), yielding an excess hospital stay among cases of
      32.1 days. The excess mortality among cases compared to controls that was
      attributable to S. aureus bloodstream infection was 45.2%. Cases had a higher
      risk of dying compared to controls (OR 7.3, 95% CI 3.1-21.1). Overall costs of
      hospitalization (SIH/SUS) reached US$ 123,065 for cases versus US$ 40,247 for
      controls (p<0.01). The cost of antimicrobial therapy was 6.7 fold higher for
      cases compared to controls. Healthcare-associated S. aureus BSI was associated
      with statistically significant increases in length of hospitalization,
      attributable mortality, and economic burden. Implementation of measures to
      minimize the risk of healthcare-associated bacterial infections is essential.

PMID- 23158267
TI  - [Challenges in translational medicine: application of the research findings in
      community].

PMID- 23158268
TI  - [Obesity and insulin resistance].

PMID- 23158269
TI  - [Chronic obstructive pulmonary disease: severity, activity and biomarkers].

PMID- 23158270
TI  - [Associations of glycated albumin level with coronary artery disease].
AB  - OBJECTIVE: To explore the associations of the level of glycated albumin (GA) with
      coronary artery disease (CAD). METHODS: A total of 306 patients undergoing
      coronary angiography (CA) were collected. There were 201 males and 105 females
      with an age range of 38-86 years. CA was the major diagnostic criteria of CAD.
      Metabolic syndrome was diagnosed according to the Guideline on Prevention &
      Treatment of Blood Lipid Abnormality in Chinese Adults. RESULTS: (1) CAD was
      found in 227 patients (74.2%). The levels of 2 h postprandial glucose, GA and
      hemoglobin A1c in the CAD patients were higher than those in the non-CAD
      counterparts (all P < 0.05). (2) In the subgroup of normal glucose tolerance
      (NGR), the CAD patients had a higher level of GA than the non-CAD patients ((15.0
      +/- 2.1)% vs (13.3 +/- 1.7)%, P < 0.01). And the level of GA was higher in the
      patients with 1-vessel ((14.8 +/- 2.1)% vs (13.3 +/- 1.7)%, P < 0.05) and multi
      vessel lesions ((15.1 +/- 2.1)% vs (13.3 +/- 1.7)%, P < 0.05) than that in the
      non-CAD counterparts (all P < 0.05). Similar results were obtained in the
      hyperglycemia subgroup. (3) Logistic regression demonstrated that the level of GA
      was independently correlated with CAD after adjusting other traditional factors
      among all subjects, NGR and hyperglycemia subgroup. CONCLUSIONS: The serum level
      of GA becomes significantly elevated the CAD patients. And it is an independent
      risk factor of CAD in both hyperglycemic and NGR patients.

PMID- 23158271
TI  - [Protection effect and mechanism of Compound Xueshuantong Capsule on diabetic
      nephropathy rats].
AB  - OBJECTIVE: To explore the renoprotective effect of Compound Xueshuantong Capsule
      (XST) on diabetic rat model with nephropathy. METHODS: Twenty-eight male Sprague
      Dawley diabetic rats were induced to hyperglycaemia (3 days later, fasting blood
      glucose > 16.7 mmol/L) by peritoneal injection with streptozotocin (STZ, 50
      mg/kg). And they were divided into four groups: diabetic nephropathy (vehicle
      treatment), irbesartan (20 mg*kg(-1)*d(-1)), low-dosage XST (900 mg*kg(-1)*d(-1))
      and high-dosage XST (1800 mg*kg(-1)*d(-1)). Seven normal rats were used as
      control. After a 12-week intervention, urine protein was examined. Pathological
      morphology was observed by hematoxylin-eosin (HE), Masson and (periodic acid
      Schiff) PAS stains. Blood nitric oxide (NO), malondialdehyde (MDA) and blood
      superoxide dismutase (SOD) and urine SOD were detected. And the expression of
      (matrix metalloproteinase-2) MMP-2 was detected by Western blot in each group.
      RESULTS: The model rats presented with hyperglycemia, polydipsia, hyperphagia,
      polyuria and hyper microalbuminuria. The intervention groups showed decreased
      microalbuminuria and there was no effect on blood glucose or body weight.
      Glomerular sclerosis and extracellular matrix (ECM) increased in model group and
      improved in irbesartan and XST groups as judged by HE, Masson and PAS stains.
      Three intervention groups had no effect on the elevated expression of MMP-2 in
      diabetic rats. Compared with the model group, the irbesartan, low-dosage and high
      dosage XST groups had significantly decreased blood levels of NO ((104.9 +/-
      11.0) umol/L vs (41.9 +/- 9.6) umol/L and (14.7 +/- 1.9) umol/L, P < 0.05) and
      MDA ((19.6 +/- 1.6) nmol/L vs (6.6 +/- 0.9) mol/L and (4.5 +/- 1.2) nmol/L, P <
      0.05), increased blood and urine activities of SOD (blood: (222 +/- 20)*10(3) vs
      (231 +/- 18)*10(3) and (237 +/- 24)*10(3) U/L,P < 0.05), urine: (11.8 +/-
      1.1)*10(3) vs (23.3 +/- 2.0)*10(3) and (25.7 +/- 1.8)*10(3) U/L). CONCLUSION:
      Compound Xueshuantong Capsule may decrease proteinuria through its suppression of
      oxidative stress and not its improvement of ECM metabolism.

PMID- 23158272
TI  - [Protective effects of astragaloside IV on high-glucose-induced damage of retinal
      ganglion cells].
AB  - OBJECTIVE: To explore the protective effects of astragaloside IV on retinal
      ganglion cells (RGC) incubated under high glucose. METHODS: Cultured RGC-5 were
      divided into 3 groups: control, high glucose and high glucose+astragaloside IV.
      The survival rate of cell was measured by CCK-8 kit and flow cytometry. The
      changes of mitochondrial membrane potential were monitored by confocal laser
      scanning microscopy while those of RGC-5 mitochondria observed by electron
      microscopy. RESULTS: When the cell survival rate was 100% in the control group,
      the survival rate improved after 1 h 5, 10, 50, 100, 200 ug/ml astragaloside IV
      pretreatment and high-glucose culture. The cell survival rates for 100 mg/L, 200
      mg/L of astragaloside IV were 81.6%, 80.0%, the difference from the high glucose
      group (66%) was significant (P < 0.05) and 100 mg/L of astragaloside IV was the
      best protection concentration. The apoptotic rate for 100 mg/L astragaloside IV
      pretreated group of RGC-5 cell was 6.1%. And it could partially inhibit the RGC-5
      cell apoptosis caused by high glucose (8.2%) (P < 0.05). In the high-glucose
      group, the cells showed marked increases in mitochondrial swelling, especially
      for cristae. Numerous normal mitochondria were observed in 100 mg/L astragaloside
      IV pretreated group. Astragaloside IV could elevate mitochondrial membrane
      potential and alleviate mitochondrial swelling. CONCLUSION: Astragaloside IV can
      protect RGC from high-glucose induced damage and may benefit the patients with
      diabetic retinopathy.

PMID- 23158273
TI  - [Ilaprazole based bismuth-containing quadruple regimen for the first-line
      treatment of Helicobacter pylori infection: a multicenter, randomized, controlled
      clinical study].
AB  - OBJECTIVE: To explore the effects of 7-day quadruple regimen as the first-line
      therapy strategy for Helicobacter pylori(H. pylori)infection and compare the
      eradication rate of ilaprazole versus esoprazole-based regimen. METHODS: A total
      of 440 patients with H. pylori infection, who had never received H. pylori
      eradication treatment, were enrolled from 10 domestic hospitals from October 2010
      to July 2011. Diagnosed as chronic gastritis or duodenal ulcer according to their
      endoscopic examination results, they were randomized into ilaprazole and(or)
      esoprazole-based bismuth-containing quadruple regimen group with amoxicillin and
      clarithromycin (n = 110 each). After a 7-day eradication treatment, all patients
      with duodenal ulcer received PPI (ilaprazole and(or) esoprazole) treatment for 14
      days and (13)C urea breath test was performed at least 28 days after the end of
      therapy. The patients with failed eradication treatment underwent endoscopy
      examination and biopsy. H. pylori culture and detection of antibiotic-resistant
      genes were also performed. RESULTS: In gastritis patients, the eradication rate
      (per-protocol, PP value) were 78.2% (79/101) and 82.0% (82/100) in ilaprazole and
      esoprazole groups (P = 0.50) while the (intention-to-treat) ITT value of
      eradication rate were 71.8% (79/110) and 74.5% (82/110) in ilaprazole and
      esoprazole groups respectively (P = 0.65). And there was no statistical
      difference (P > 0.05). In duodenal patients, the eradication rate (PP) were 92.1%
      (93/101) and 91.4% (96/105) in ilaprazole and esoprazole group (P = 0.86) while
      the ITT value of eradication rate were 84.5% (93/110) and 87.3% (96/110) in
      ilaprazole and esoprazole groups respectively (P = 0.56). And no significant
      difference existed between two groups in gastritis and duodenal ulcer patients (P
      > 0.05). In total, the eradication rate was 80.1% (161/201) (PP) and 73.2%
      (161/220) (ITT), 91.7% (189/206) (PP) and 85.9% (189/220) (ITT) in chronic
      gastritis and duodenal ulcer patients respectively. The symptomatic improvements
      of stomachache, burning, belching and nausea remained almost unchanged. No severe
      side effect was observed. The point mutations for clarithromycin resistance were
      detected in all 53 H. pylori strains (100%) isolated from the patients with
      failed eradication treatment. CONCLUSIONS: The eradication rate of PPI based
      bismuth-containing quadruple regimen as the first-line treatment is satisfactory
      in chronic gastritis and duodenal ulcer patients. No significant difference
      exists between the effects of ilaprazole and esoprazole-based groups. And the
      treatment failure may be attributed mainly to the clarithromycin resistance of H.
      pylori.

PMID- 23158274
TI  - [Selection of radical operative modalities for proximal gastric cancer].
AB  - OBJECTIVE: To evaluate the rationality of different radical operative modalities
      for proximal gastric cancer. METHODS: A total of 366 cases of proximal gastric
      cancer undergoing radical dissection were screened from data base. According to
      the operative modalities, they were divided into proximal gastrectomy group (PG)
      (n = 77) and total gastrectomy group (TG) (n = 289). Through the comparisons of
      clinical pathologic features, surgical profiles, postoperative complications,
      postoperative quality-of-life and prognosis in two groups, the rationality of
      different operative modalities was evaluated. RESULTS: No significant differences
      existed in age, gender or carcinoembryonic antigen (CEA) value between two groups
      (all P > 0.05). The rates of tumor diameter >= 5 cm, organic infiltration, lymph
      nodes metastasis, distal organs metastasis, infiltrative type, poorly
      differentiated tumor in PG and TG groups were 15.6% (12/77) vs 49.8% (144/289),
      16.9% (13/77) vs 37.7% (109/289), 67.5% (52/77) vs 79.9% (231/289), 3.9% (3/77)
      vs 11.4% (33/289), 45.5% (35/77) vs 68.9% (199/289), 32.5% (25/77) vs 57.8%
      (167/289) respectively (all P < 0.05). Operative duration, volume of blood
      transfusion, number of dissected lymph nodes and positive lymph nodes, rate of
      combined organic resection and complications in groups of PG and TG were (256 +/-
      83) vs (298 +/- 86)min, 0 vs 400 ml, 15 +/- 12 vs 26 +/- 15, 0 vs 3, 15.6%
      (12/77) vs 43.2% (125/289), 14.3% (11/77) vs 7.6% (22/289) respectively (all P <
      0.05). In two groups, the evaluating indices of postoperative quality-of-life
      showed no significant differences (P > 0.05). In two groups, the median survival
      time of the cases with tumor diameter < 5 cm, no-organic infiltration, no-peri
      tumor lymph nodes metastasis, no-distal organic metastasis had no significant
      difference (all P > 0.05). However, in groups of PG and TG, the median survival
      time of the cases with tumor diameter >= 5 cm, organic infiltration, peri-tumor
      lymph nodes metastasis and distal organic metastasis was 15.0 months vs 29.0
      months, 15.0 months vs 30.0 months, 34.0 months vs 45.0 months, 4.0 months vs
      18.0 months respectively(all P < 0.05). CONCLUSION: As compared with radical
      proximal gastrectomy, radical total gastrectomy improves significantly the
      prognosis of patients of proximal gastric cancer with organic infiltration, peri
      tumor lymph nodes metastasis, distal organic metastasis and tumor diameter >= 5
      cm.

PMID- 23158275
TI  - [Long-term effects of permanent pacemaker implantation on tricuspid valve
      regurgitation].
AB  - OBJECTIVE: To explore the long-term effects of permanent pacemaker implantation
      (PPI) on tricuspid valve regurgitation (TR) in Chinese patients so as to
      determine the incidence and related factors, evaluate its effects on heart
      structure and function and ascertain the exact mechanism of TR after PPI.
      METHODS: A total of 430 patients undergoing permanent pacemaker replacement at
      our hospital between January 2000 and June 2011 were recruited. The patients with
      isolated atrial lead implantation procedures, significant heart valve disease or
      chronic obstructive pulmonary disease were excluded. The data of 108 patients who
      had Doppler echocardiograms performed before the first pacemaker implantation
      procedure and this pacemaker replacement procedure were obtained and
      retrospectively analyzed. According to the post-implant grade of TR, the patients
      were divided into two groups: normal tricuspid (n = 79) and abnormal tricuspid (n
      = 29). Their clinical characteristics and echocardiographic data between two
      groups were analyzed and compared. RESULTS: The mean follow-up time (from the
      first pacemaker implantation) was (13 +/- 6) years (range: 4 - 34). Among 108
      patients with initially normal tricuspid post-implant, 29 patients (26.9%)
      developed significant TR during the follow-up. In comparison to those in normal
      tricuspid group, the patients in abnormal tricuspid group had a longer time from
      the first pacemaker implantation ((16 +/- 7) vs (12 +/- 5) years, P = 0.003),
      more transtricuspid leads (1.31 +/- 0.66 vs 1.10 +/- 0.30, P = 0.026), larger
      right atrial size ((38 +/- 7) vs (35 +/- 4) mm, P = 0.028) and higher prevalence
      of mild TR and mitral valve regurgitation (MR) pre-implantation (TR: 21% vs 4%, P
      = 0.015, MR: 28% vs 5%, P = 0.003). The size of right atrium, right ventricle and
      left atrium in abnormal tricuspid group were more than those in normal tricuspid
      group. The prevalence of significant MR post-implantation in abnormal tricuspid
      group was higher than that in normal tricuspid group. The ejection fraction in
      abnormal tricuspid group was lower than that in normal tricuspid group during the
      follow-up. CONCLUSIONS: Abnormal TR after PPI during a long-term follow-up is
      quite common. The related factors include the time interval from the first
      pacemaker implantation, number of transtricuspid lead, right atrial size, mild TR
      and MR pre-implantation.

PMID- 23158276
TI  - [Effect and mechanism of RetroNectin on the proliferation and cytotoxic activity
      of acute leukemia natural killer cells].
AB  - OBJECTIVE: To explore the effects of precoated RetroNectin on the proliferation
      and cytotoxicity of natural killer cells (NK) from acute leukemia (AL). METHODS:
      Mononuclear cells (MNCs) were isolated from peripheral blood of complete
      remission AL patients. The MNCs were cultured in vitro precoated with 50 ug/ml
      RetroNectin (group I), 25 ug/ml RetroNectin (group II) and by the traditional
      method (control group) to generate NK. The changes of growth rate, phenotypic
      characterization, secretion of cytokines of NK, cell cycle, apoptosis and
      cytotoxicity of NK were determined. RESULTS: The amplification of NK in group I
      ((51 +/- 9)*10(6)) and II ((79 +/- 16) *10(6)) were higher than that in control
      group ((37 +/- 11)*10(6)) (both P < 0.05), and the amplification of NK in groupII
      was higher than that in group I (P < 0.05). There were no differences among three
      groups with regards to the phenotypic characterization of CD3(-)CD56(+). The
      secretions of interleukin 2, interleukin 12, tumor necrosis factor alpha and
      interferon gamma in group I and II were higher than that in control group (all P
      < 0.05). The expression of CD25 positive cells in groups I (38.2% +/- 4.1%) and
      II (37.5% +/- 5.1%) were higher than that in control group (24.2% +/- 5.8%) (both
      P < 0.05). The expression of NKG2D positive cells in groups I (81.6% +/- 17.9%)
      and II (85.7% +/- 20.1%) were higher than that in control group (63.6% +/- 21.9%)
      (both P < 0.05). The percentages of G(1) stage cells in groups I (50% +/- 10%)
      and II (49% +/- 11%) were lower than that in control group (71% +/- 15%) while
      the percentages of S stage cells in groups I (36% +/- 14%) and II (37% +/- 8%)
      were higher than that in control group (19% +/- 10%) (all P < 0.05). But no
      difference existed between two groups (all P > 0.05). The expression of cell
      cycle regulatory genes p21 and p27 were reduced in groups I and II. The
      percentages of apoptotic cells in groups I (10.7% +/- 2.1%) and II (9.4% +/-
      3.1%) were lower than that in control group (29.6% +/- 10.3%) (both P < 0.05).
      The cytotoxicity to AL cells in groups I (82% +/- 21%) and II (80% +/- 18%) were
      higher than that in control group (61% +/- 14%) (both P < 0.05) at the E/T scope
      20:1. But no difference existed between two groups (all P > 0.05). CONCLUSION:
      The proliferation and cytotoxicity of NK cells may be boosted by precoated
      RetroNectin.

PMID- 23158277
TI  - [Relationship between anxiety, depression and asthma control].
AB  - OBJECTIVE: To explore the relationship between psychological status of depression
      and anxiety and asthma control. METHODS: A total of 144 definite physician
      diagnosed asthmatics at First Affiliated Hospital, Zhengzhou University from
      March 2011 to March 2012 were evaluated with the self-rating anxiety scale (SAS)
      and self-rating depressive scale (SDS). And 85 healthy subjects were selected as
      the controls and evaluated by the asthma control test (ACT). The incidence of
      anxiety and depression and scores of SAS and SDS was compared between the asthma
      group and health controls. The relationship was analyzed between the scores of
      ACT and SAS or SDS respectively. The subjects were divided into anxiety, non
      anxiety, depression and non-depression groups according to the scores of SAS and
      SDS. The inter-group differences in ACT scores were compared. According to the
      asthma control test scale, the asthmatics were divided into the control, non
      control and partial control groups. And the inter-group differences in the scores
      of SAS and SDS were compared. RESULTS: Anxiety (20.1%) and depression (35.4%) was
      more common in asthmatics than healthy controls (both P < 0.01). Scores of SAS
      (40.8 +/- 8.1) and SDS (44.9 +/- 9.1) in physician-diagnosed asthmatics were
      higher than the controls and general community (both P < 0.01). Scores of ACT in
      non-anxiety group (18.6 +/- 4.4) were higher than those in anxiety group, higher
      in non-depression group (18.5 +/- 4.6) than depression group (both P < 0.01).
      Scores of SAS (control group: 33.6 +/- 4.3, non-control group: 43.7 +/- 7.8 and
      partial control group: 37.6 +/- 7.1) and SDS (control group: 35.1 +/- 6.7, non
      control group: 47.2 +/- 9.7 and partial control group: 43.3 +/- 6.6) in physician
      diagnosed asthmatics varied among different control levels (both P < 0.01). The
      anxiety, depression scores and ACT scores were negatively correlated in
      asthmatics (r = 0.52 and 0.23, both P < 0.01). With the rising scores of SAS and
      SDS, ACT score decreases (b = -0.29 and -0.12, both P < 0.01). CONCLUSIONS:
      Anxiety and depression moods are more common in asthmatics than healthy controls.
      The worse asthma control, the more severity of anxiety and depression, and vice
      versa.

PMID- 23158278
TI  - [Application of absorbable plate in oral maxillofacial fractures].
AB  - OBJECTIVE: To explore the biological features and clinical efficacies of
      absorbable plates and screws for rigid internal fixation. METHODS: From June 2006
      to June 2010, 201 FIXSORB(TM)-MX absorbable plates were used in 57 patients,
      including 41 males and 16 females aged from 11 - 81 years. And 185 plates were
      used in 53 patients of maxillofacial fracture and 16 plates in 4 undergoing
      orthognathic operations with rigid internal fixation. RESULTS: All wounds healed
      primarily and there were no major complications. Forty-five cases were followed
      up for an average period of 12 months (range: 3 - 36). No obvious adverse effect
      and absorbable implants rejection were observed. The fracture lines were in the
      right position in 56 cases. CONCLUSION: As a kind of fine material for internal
      fixation with strong elasticity and strength, absorbable plate shall be widely
      used clinically.

PMID- 23158279
TI  - [Effects of hRAMP1 modified mesenchymal stem cells on restenosis and heart
      function in rabbit model of carotid angioplasty and myocardial infarction].
AB  - OBJECTIVE: To observe the effects of mesenchymal stem cells (MSC) modified by
      human receptor activity-modifying protein 1 (hRAMP1) on restenosis and cardiac
      function post-myocardial infarction (MI) and explore the therapeutic safety for
      gene modification of MSC. METHODS: The double-injury rabbit model with MI
      reperfusion and sacculus damaged atherosclerotic carotid were established
      according to the previous study. MSC were transfected with adenovirus vector with
      enhanced green fluorescence protein (EGFP) and then introduced into rabbit model.
      The animals were randomly divided into Ad-EGFP-hRAMP1-MSC transfection group
      (hRAMP1-MSC group, n = 24) and Ad-EGFP-MSC transfection group (MSC group, n =
      24), and PBS transfection group (C group, n = 24). At Day 28 post
      transplantation, the injured carotid arteries and infarction myocardium were
      harvested to detect the expression of EGFP-positive MSC and assess organization
      morphology by hematoxylin and eosin, triphenyltetrazolium chloride or
      immunohistochemical stains and heart function by echocardiography. RESULTS: On
      flow cytometry, most cells expressed CD29 and CD90 while few ones expressed CD45.
      MSC with EGFP and a continuous expression of CD31 were found in intima of damaged
      carotid of both hRAMP1-MSC and MSC, but the expression of EGFP was not found in
      the control group. At Day 28 post-transplantation, the improvement of heart
      function and the decrease of infarct size were found in the hRAMP1-MSC and MSC
      groups compared with that in the control group(EF: 60.6% +/- 1.5%,50.8% +/- 3.2%
      vs 38.2% +/- 2.0%, infarct size: 20.7% +/- 1.4%, 33.2% +/- 3.7% vs 35.6% +/-
      2.7%, all P < 0.05), especially much higher in hRAMP1-MSC group. At Day 28 post
      transplantation, the area of intima hyperplasia and the rate of neointima and
      media in the hRAMP1-MSC group were lower than those in the MSC and C groups (0.15
      +/- 0.05 and 0.33 +/- 0.08 vs 0.77 +/- 0.11, 0.24 +/- 0.07 and 0.51 +/- 0.11 vs
      1.09 +/- 0.23, all P < 0.05). Also the expression of alpha-SMA was found in the
      hyperplasia intima. The expression of proliferating cell nuclear antigen
      significantly decreased in the hRAMP1-MSC group than those of the MSC and control
      groups (0.120 +/- 0.028 vs 0.366 +/- 0.013 and 0.627 +/- 0.049, both P < 0.05).
      And it was much lower in the MSC group than that in the control group.
      CONCLUSIONS: Compared with MSC alone, hRAMP1-modified MSC have the potency not
      only of more improvement on cardiac function and the recovery of damaged
      endothelium, but also of significant inhibition of the proliferation of vascular
      smooth muscle cells. The recombinant hRAMP1 adenovirus vectors do not affect the
      differentiation potential MSC into endothelial cells.

PMID- 23158280
TI  - [Regulation of p14(ARF) expression and induction of cell apoptosis with c-myc in
      a p53-independent pathway].
AB  - OBJECTIVE: To explore the regulation of p14(ARF) expression and induction of cell
      apoptosis with the mutant and wild-type c-myc genes in a p53-independent pathway
      of signal transduction. METHODS: The mutant and wild-type c-myc genes were
      transfected by lentivirus into HCC1937 to form the stable over-expression cell
      lines. Uninfected cells and lentivirus-infected ones carrying no c-myc gene acted
      as blank and infection controls respectively. And c-myc and p14(ARF) mRNA and
      protein, proliferation and apoptosis in HCC1937 with mutant and wild-type c-myc
      were detected by reverse transcription (RT)-PCR, Western blotting, thiazolyl blue
      tetrazolium bromide (MTT) and terminal deoxynucleotidyl transferase mediated X
      dUTP nick end labeling (TUNEL) respectively. RESULTS: After the lentivirus
      mediated gene transfer, c-myc mRNA and protein expression increased in the mutant
      and wild-type groups. p14(ARF) mRNA and protein increased in the wild-type group
      and the mutant group and there were significant difference between them with
      blank and infection controls (mutant groups: 0.560 +/- 0.010, 0.154 +/- 0.011,
      wild-type groups: 0.651 +/- 0.010, 0.382 +/- 0.013, both P < 0.05). The group of
      mutant and wild-type c-myc could promote the proliferation of cell growth. And c
      myc was more effective to induce apoptosis in the wild-type group as compared
      with the mutant group (7.1% +/- 0.7% vs 3.2% +/- 0.4%, P < 0.05). CONCLUSIONS: In
      a p53-independent pathway, the over-expression of wild-type c-myc obviously up
      regulates the expression of p14(ARF). And cell apoptosis may be induced through
      the regulation of p14(ARF)-related gene, keep balance of proliferative promotion
      and apoptosis induction. When there is a loss-of-function of mutant c-myc,
      tumorigenicity increases via a disturbed balance of proliferative promotion and
      apoptosis induction.

PMID- 23158281
TI  - [Protective effects of rosiglitazone intervention on monocrotaline-induced
      pulmonary arterial hypertension in rats and related inflammatory mechanisms].
AB  - OBJECTIVE: To investigate the protective effects of rosiglitazone intervention on
      monocrotaline (MCT)-induced pulmonary arterial hypertension (PAH) in rats and the
      possible mechanisms. METHODS: Thirty-two Sprague-Dawley rats were randomly
      divided into 4 groups: control group with a subcutaneous injection of normal
      saline. PAH group, high-dose and low-dose rosiglitazone intervention groups all
      with a subcutaneous injection of MCT and then gastric infusion of normal saline
      (1.5 ml/d), rosiglitazone (5, 2.5 mg.kg(-1)*d(-1)). At Day 21, the mean pulmonary
      arterial pressure (mPAP) was detected by right heart catheter. Then rats were
      sacrificed and their lungs extracted. Perivascular inflammation was scored with
      the subjective scale of 0 to 4. The tunica media thickness percentage of small
      pulmonary arteries (WT%) of rats was calculated. Interleukin 6 (IL-6), tumor
      necrosis factor alpha (TNF-alpha) and monocyte chemotactic protein 1 (MCP-1) of
      lung tissue were detected by enzyme-linked immunosorbent assay (ELISA). RESULTS:
      Compared with the PAH group ((37 +/- 5) mm Hg (1 mm Hg = 0.133 kPa), 45.5% +/-
      5.5%), the mPAP and WT% of the high-dose ((27 +/- 4) mm Hg, 13.1% +/- 3.9%) and
      low-dose ((28 +/- 4) mm Hg, 16.7% +/- 1.7%) rosiglitazone intervention group were
      significantly lower (P < 0.01), but were still higher than those of the control
      group ((17 +/- 3) mm Hg, 8.9% +/- 2.3%) (P < 0.05 or P < 0.01). The perivascular
      inflammation score and levels of IL-6, TNF-alpha, MCP-1 of high-dose and low-dose
      rosiglitazone intervention groups were significantly lower than those of the PAH
      group (P < 0.01). Compared with the low-dose rosiglitazone intervention group,
      all the above indices of the high-dose rosiglitazone intervention group appeared
      much lower (P > 0.05). CONCLUSION: The protective effects of rosiglitazone
      against MCT-induced PH are correlated with drug dose and may be due to the
      inhibition of inflammation.

PMID- 23158282
TI  - [Transvaginal appendectomy with traditional laparoscopic tools].
AB  - OBJECTIVE: To establish the technique and methodology of appendectomy through
      transvaginal natural orifice transluminal endoscopic surgery(NOTES)under
      laparoscopy. METHODS: Three cases of chronic appendicitis were selected to
      receive laparoscopic transvaginal resection of appendixes with concurrent vaginal
      hysterectomies for uterine fibroids at Shengjing Hospital of China Medical
      University from November 2010 to November 2011. The procedure was performed by a
      multidisciplinary team composed of surgeons and gynecologists. The clinical data
      such as operative duration, bleeding volume, morbidity and stay duration were
      collected and analyzed. RESULTS: Appendectomies were performed with the working
      laparoscopic tools inserted through vagina. The en bloc resection was removed
      transvaginally through laparoscope. It took 34, 23 and 26 minutes respectively to
      complete the appendectomies. And the blood loss volume was minimal. There were no
      postoperative complications. And the patients were discharged scar-free after 3
      days. CONCLUSIONS: Transvaginal appendectomy is both feasible and safe when
      performed by a multidisciplinary team. As an emerging innovation, natural orifice
      transluminal endoscopic surgery is mini-invasive, better tolerated and more
      respectful of esthetics.

PMID- 23158283
TI  - Improved sample treatment for the determination of bisphenol A and its
      chlorinated derivatives in sewage sludge samples by pressurized liquid extraction
      and liquid chromatography-tandem mass spectrometry.
AB  - A selective, sensitive, robust and accurate method for the determination of
      bisphenol A (BPA) and its chlorinated derivatives in sewage sludge samples using
      liquid chromatography-tandem mass spectrometry (LC-MS/MS) is presented. Prior to
      instrumental analysis, an extraction procedure using pressurized liquid
      extraction (PLE) was carried out in order to obtain the highest recoveries and
      improve sensitivity. After LC separation, the MS conditions, in negative
      atmospheric pressurized chemical ionization (APCI) mode, were individually
      optimized for each analyte to obtain maximum sensitivity in the selected reaction
      monitoring (SRM) mode. The use of two reactions for each compound allowed
      simultaneous quantification and identification in one run. The analytes were
      separated in less than 6 min. BPA-d(16) was used as internal standard. The limits
      of detection of the method ranged from 4 to 8 ng g(-1) and the limits of
      quantification from 14 to 26 ng g(-1), while inter- and intra-day variability was
      under 6% in all cases. Due to the absence of certified materials, the method was
      validated using matrix-matched calibration and a recovery assay with spiked
      samples. Recovery rates ranged from 97.7% to 100.6%. The method was
      satisfactorily applied for the determination BPA and its chlorinated derivatives
      in sewage sludge samples collected from wastewater treatment plants (WWTPs)
      located in the province of Granada (Spain). The sludge samples came from a
      conventional activated sludge (AS) plant and from a membrane bioreactor (MBR)
      pilot plant.

PMID- 23158284
TI  - Detection of nitric oxide in macrophage cells for the assessment of the
      cytotoxicity of gold nanoparticles.
AB  - In this paper, an electrochemical method using a nitric oxide sensor was employed
      for quantitative evaluation of NO released from AuNPs-treated macrophage cells.
      Our results indicate that the AuNPs initiate NO release from macrophage cells and
      the amount of NO released is positively correlated with concentration of AuNPs.
      Meanwhile, total nitrite/nitrate concentrations in the AuNPs-treated macrophage
      cells have been determined via the Griess reaction and we demonstrate that the
      variation of the nitrite/nitrate concentrations is in accordance with that
      measured by the electrochemical method. In contrast to the citrate-coated gold
      nanoparticles (CT-AuNPs), when AuNPs were protected by thiolated poly ethylene
      glycol (PEG), the NO-releasing in macrophage upon the addition of AuNPs was
      relieved, implying that the PEG-coated AuNPs having less cytotoxicity and
      oxidative stress potential is probably due to inhibition of NO production. In
      conclusion, this work has demonstrated an effective sensing platform for the
      evaluation of the cytotoxicity of AuNPs by detecting the extracellular NO
      released from macrophage cells.

PMID- 23158285
TI  - Temperature dependence of ion mobility signals of halogenated compounds.
AB  - Ion mobility spectrometry (IMS) as handheld and transportable sensor technique
      permits the sensitive detection of halogenated compounds with importance in
      environmental monitoring and process control. The negative ion mobility spectra
      mostly show one product ion peak which can be attributed to (H(2)O)(n)X(-) ions
      due to dissociative electron attachments. For minimizing memory effects and
      contaminations, modern ion mobility spectrometers work at elevated temperatures.
      In this paper, we investigated the influence of temperature on peak position,
      resolution and relative abundance of ions formed from halogenated substances.
      Elevated temperatures affect the peak position in different way. For fluorine-
      and chlorine-containing product ions, changes in hydration and clustering have a
      considerable influence on peak position, while these processes are of minor
      importance for bromine- and iodine-containing product ions. In these cases, the
      drift time differences mainly result from differences in drift behavior due to
      differences in gas density, the mean free path of ions and different collision
      rates. The drift time shift with elevated temperatures provides an enhanced peak
      to-peak resolution. Improved separation efficiency can therefore be established
      with increased temperatures for negative product ions of halogenated compounds.
      Furthermore, an enhanced sensitivity was found for all compounds with increasing
      temperatures. However, independent on the temperature, the order of sensitivity
      is mainly determined by the bonding state of halogen atoms within the molecules.

PMID- 23158286
TI  - Improvement of sensitive CuO NFs-ITO nonenzymatic glucose sensor based on in situ
      electrospun fiber.
AB  - CuO nanofibers (NFs), prepared by electrospinning and calcination technologies,
      have been applied for the fabrication of glucose sensors with high sensitivity
      and selectivity. Cu(NO(3))(2) and polyvinylpyrrolidone (PVP) composite nanofibers
      were initially electrospun on the surface of indium tin oxide (ITO) glass, and
      then the CuO NFs-ITO electrode was formed simply by removing PVP through heat
      treatment. The structures and morphologies of CuO nanofibers were characterized
      by X-ray diffraction, scanning electron microscopy and thermogravimetric
      analysis. The direct electrocatalytic oxidation of glucose in alkaline medium at
      CuO NFs-ITO electrode has also been investigated in detail with cyclic
      voltammetry, chronoamperometry and electrochemical impedance spectroscopy. The
      effects of NaOH concentration, electrospinning time, Cu(NO(3))(2):PVP mass ratios
      and calcination temperature on the response to glucose were investigated. Under
      optimized experimental conditions, the CuO NFs-ITO electrode produced high and
      reproducible sensitivity to glucose of 873 MUA mM(-1)cm(-2). Linear responses
      were obtained over a concentration range from 0.20 MUM to 1.3mM with a detection
      limit of 40 nM (S/N=3). The CuO NFs-ITO electrode also has good selectivity,
      stability and fast amperometic sensing of glucose, thus it can be used for the
      future development of non-enzymatic glucose sensors.

PMID- 23158287
TI  - Folic acid as delivery vehicles: targeting folate conjugated fluorescent
      nanoparticles to tumors imaging.
AB  - Herein, folic acid (FA) conjugated with AuNPs were introduced into the cancer
      cell imaging via the specific interaction between FA and the folate receptor on
      the cell surface. FA protected gold nanoparticles (AuNPs) was synthesized and
      labeled with fluorescein isothiocynate (FITC) to form the FITC-FA-AuNPs (FFANPs).
      As over-expressed folic acid receptor in some cancer cells and folic acid can
      specifically and selectively combine, the FFANPs can bind to the FR expressed on
      tumor cells such as HeLa cells (human epithelial cervical cancer) and CERF-CEM
      cells (T cell line, human acute lymphoblastic leukemia). As a result, cancer cell
      imaging can be achieved. To ascertain the FR target ability, it has been acquired
      by FR-targeted images using synthetic FFANPs. The formation of FITC-FA can be
      identified by MS. FCM was carried out to study the cell uptake of FFANPs. The
      cell toxicity (3-[4,5-dimethylthiazolyl-2]-2, 5-diphenyltetrazolium bromide, MTT)
      assay demonstrated that the FITC-labeled conjugate had only little effect on the
      cytotoxicity to the cells, which further proved the applicability of the method
      in tumor cell imaging.

PMID- 23158288
TI  - Rapid and simultaneous determination of antioxidant markers and caffeine in
      commercial teas and dietary supplements by HPLC-DAD.
AB  - A simple and fast reverse-phase high-performance liquid chromatography procedure
      coupled with photodiode array detector (RP-HPLC-DAD) was developed and validated
      for the analysis of major catechins, proanthocyanidin (procyanidin B2) and
      caffeine in 25 different natural complex matrices containing Camellia sinensis L.
      and/or grape seed extracts, two popular plant extracts that have been widely used
      as natural antioxidants in various food and beverage applications. Using an
      isocratic elution system, separation of all compounds was achieved within 12 min.
      Excellent linearity was observed for all of the standard calibration curves, and
      the correlation coefficients were above 0.9997. Limits of detection for all of
      the analyzed compounds ranged between 2.80*10(-3) and 2.51*10(-2) MUg mL(-1);
      limits of quantitation ranged between 9.30*10(-3) and 8.36*10(-2) MUg mL(-1). The
      developed method was found to be accurate and sensitive and is ideally suited for
      rapid, routine analysis of principal components in these well-known natural
      antioxidants.

PMID- 23158289
TI  - Adsorption of heavy metal ions by hierarchically structured magnetite
      carbonaceous spheres.
AB  - Magnetically driven separation technology has received considerable attention in
      recent decade for its great potential application. In this work, hierarchically
      structured magnetite-carbonaceous microspheres (Fe(3)O(4)-C MSs) have been
      synthesized for the adsorption of heavy metal ions from aqueous solution. Each
      sphere contains numerous unique rattle-type structured magnetic particles,
      realizing the integration of rattle-type building unit into microspheres. The as
      prepared composites with high BET surface area, hierarchical as well as
      mesoporous structures, exhibit an excellent adsorption capacity for heavy metal
      ions and a convenient separation procedure with the help of an external magnet.
      It was found that the maximum adsorption capacity of the composite toward Pb(2+)
      was ~126mgg(-1), displaying a high efficiency for the removal of heavy metal
      ions. The Freundlich adsorption isotherm was applicable to describe the removal
      processes. Kinetics of the Pb(2+) removal was found to follow pseudo-second-order
      rate equation. The as-prepared composite of Fe(3)O(4)-C MSs as well as Pb(2+)
      adsorbed composite were carefully examined by scanning electron microscopy (SEM),
      Zeta potential measurements, Fourier transform infrared spectroscopy (FT-IR),
      nitrogen sorption measurements, and X-ray photoelectron spectroscopy (XPS). Based
      on the characterization results, a possible mechanism of Pb(2+) removal with the
      composite of Fe(3)O(4)-C MSs was proposed.

PMID- 23158290
TI  - Chiral recognition and quantification of propranolol enantiomers by surface
      enhanced Raman scattering through supramolecular interaction with beta
      cyclodextrin.
AB  - A simple, fast and accurate method of chiral recognition and quantification of
      propranolol enantiomers by surface enhanced Raman scattering (SERS) and
      multivariate regression analysis through supramolecular interaction with beta
      cyclodextrin is reported. Computational chemistry served as a tool of elucidating
      the underlying mechanism of molecular interactions responsible for chiral
      discrimination. The influence of several factors (nature and concentration of
      chiral auxiliary, selector-selectand ratio, pH, interaction time, etc.) over the
      obtained SERS spectra was assessed, followed by the construction of the
      chemometric model with the optimized operational conditions. The performance of
      the obtained semi-empirical model was established using a validation set of pure
      enantiomers and its intended use was demonstrated by the assessment of the
      enantiomeric excess of propranolol in pharmaceutical formulations (tablets)
      without the need of tedious and expensive chiral separation. The obtained results
      were also confirmed by chiral high-performance liquid chromatography.

PMID- 23158291
TI  - Highly selective visual distinction of pyrophosphate from other phosphate anions
      with 4-[(5-chloro-2-pyridyl)azo]-1,3-diaminobenzene in the presence of copper(II)
      ions.
AB  - Pyrophosphate (PPi), as a biologically related phosphate anion, plays very
      important roles in organisms. Here, a highly selective visual method for
      distinction of PPi was made with commercial available 4-[(5-chloro-2-pyridyl)azo]
      1,3-diaminobenzene (5-Cl-PADAB) in the presence of copper(II). The yellow
      solution of 5-Cl-PADAB exhibits strong absorption at 450.5 nm, and addition of
      Cu(II) results in a red solution with a new absorption band at 506.0 nm. Upon
      titration with PPi, the absorption band at 506.0 nm decreases with blueshift,
      while another new absorption band in the region from 562.0 nm to 750.0 nm appears
      which gradually splits into two peaks, and the color accordingly changes from red
      to cyan. Further addition of PPi, the new absorption peaks gradually disappear,
      and the mixture shows the absorption of 5-Cl-PADAB and recovers to yellow from
      cyan. This process is highly selective for PPi since other phosphate anions such
      as nucleotides cannot induce such spectral and color changes. With this method,
      the detection of PPi concentration in human urine was made with satisfactory
      results.

PMID- 23158292
TI  - Influence of variation in mobile phase pH and solute pK(a) with the change of
      organic modifier fraction on QSRRs of hydrophobicity and RP-HPLC retention of
      weakly acidic compounds.
AB  - The variation in mobile phase pH and ionizable solute dissociation constant
      (pK(a)) with the change of organic modifier fraction in hydroorganic mobile phase
      has seemingly been a troublesome problem in studies and applications of reversed
      phase high performance liquid chromatography (RP-HPLC). Most of the early studies
      regarding the RP-HPLC of acid-base compounds have to measure the actual pH of the
      mixed mobile phase rigorously, sometimes bringing difficulties in the practices
      of liquid chromatographic separation. In this paper, the effect of this variation
      on the apparent n-octanol/water partition coefficient (K(ow)") and the related
      quantitative structure-retention relationship (QSRR) of logK(ow)" vs. logk(w),
      the logarithm of retention factor of analytes in neat aqueous mobile phases, was
      investigated for weakly acidic compounds. This QSRR is commonly used as a
      classical method for K(ow) measurement by RP-HPLC. The theoretical and
      experimental derivation revealed that the variation in mobile phase pH and solute
      pK(a) will not affect the QSRRs of acidic compounds. This conclusion is proved to
      be suitable for various types of ion-suppressors, i.e., strong acid (perchloric
      acid), weak acid (acetic acid) and buffer salt (potassium dihydrogen
      phosphate/phosphoric acid, PBS). The QSRRs of logK(ow)" vs. logk(w) were modeled
      by 11 substituted benzoic acids using different types of ion-suppressors in a
      binary methanol-water mobile phase to confirm our deduction. Although different
      types of ion-suppressor all can be used as mobile phase pH modifiers, the QSRR
      model obtained by using perchloric acid as the ion-suppressor was found to have
      the best result, and the slightly inferior QSRRs were obtained by using acetic
      acid or PBS as the ion-suppressor.

PMID- 23158293
TI  - Penicillin analyses by capillary electrochromatography-mass spectrometry with
      different charged poly(stearyl methacrylate-divinylbenzene) monoliths as
      stationary phases.
AB  - This study describes the ability of an on-line concentration capillary
      electrochromatography (CEC) coupled with mass spectrometry (MS) for the
      determination of eight common penicillin antibiotics. Poly(stearyl methacrylate
      divinylbenzene) (poly(SMA-DVB)) based monolithic columns prepared under the same
      conditions but differing only in the charged monomer were used as separation
      columns. Vinylbenzyl trimethylammonium chloride (VBTA) and vinylbenzenesulfonate
      (VBSA) were employed as the positively charged monolith and negatively charged
      monolith, respectively. Results indicated that poly(SMA-DVB-VBTA) monolithic
      column provided reproducible performance for penicillin separation through ion
      exchange interaction, while the negatively charged poly(SMA-DVB-VBSA) column
      produced unstable separation due to the electrostatic repulsion between the
      electrophilic analytes and the negatively charged stationary phase. On-line
      concentration steps of step-gradient elution combined with anion selective
      injection (ASEI) were used to enhance the detection sensitivity of the CEC-MS
      method and all penicillin detection sensitivities were further improved
      (reduction in the limits of detection from 1.9-31 MUg/L (normal injection mode)
      to 0.05-0.2 MUg/L (on-line concentration mode)). Finally, this optimal on-line
      concentration CEC-MS method was applied to trace penicillin analyses in milk
      samples.

PMID- 23158294
TI  - Simultaneous determination of Solvent Yellow 124 and Solvent Red 19 in diesel oil
      using fluorescence spectroscopy and chemometrics.
AB  - Differences in tax levels for diesel oil stimulate the illegal removal of
      characteristic diazo compounds purposely added to designate its possible usage.
      In order to reduce the losses in the national income, there is a strong need to
      develop a sensitive and cost-effective analytical procedure for the detection of
      this illegal action. In this study, we describe a novel analytical approach for a
      qualitative and quantitative determination of two diazo compounds (Solvent Yellow
      124 and Solvent Red 19) that are usually added to diesel oil. The methodology
      proposed combines the use of excitation-emission matrix fluorescence spectroscopy
      as an analytical technique and partial least squares regression as a multiple
      modeling tool. With this new methodology, relatively low root mean square errors
      of prediction (for independent set of test samples) that are equal to 0.223 for
      Solvent Red 19 and 0.263 for Solvent Yellow 124, were obtained and the results
      were stable, which were indicated by an analysis performed after 48 and 96 h. The
      methodology is also nondestructive and allows for (i) simultaneous detection of
      diesel oil additives, (ii) determination of satisfactory limits of detection
      (0.048 and 0.042 mg L(-1) for Solvent Red 19 and Solvent Yellow 124,
      respectively), and (iii) obtaining of considerably low relative standard
      deviations of 2.33% for Solvent Yellow 124 and of 3.23% for Solvent Red 19 in
      comparison with the existing norm level.

PMID- 23158295
TI  - Strip-based immunoassay for the simultaneous detection of the neonicotinoid
      insecticides imidacloprid and thiamethoxam in agricultural products.
AB  - A semiquantitative strip immunoassay was developed for the rapid detection of
      imidacloprid and thiamethoxam in agricultural products using specific
      nanocolloidal gold-labeled monoclonal antibodies. The conjugates of imidacloprid
      BSA, thiamethoxam-BSA and goat anti-mouse IgG were coated on the nitro-cellulose
      membrane of the strip, serving as test lines and control line, respectively. The
      flow of the complexes of gold labeled antibodies and insecticides along the strip
      resulted in intensive color formed on the test lines inversely proportional to
      the concentrations of imidacloprid and thiamethoxam. The visual detection limits
      of imidacloprid and thiamethoxam in assay buffer were 0.5 and 2 ng mL(-1),
      respectively. Matrix interference of cucumber, tomato, lettuce, apple, and orange
      on the strip assay could be eliminated by diluting sample extracts with assay
      buffer. The strip analysis of imidacloprid and thiamethoxam in these samples was
      compared to liquid chromatography-mass spectrometry and the results were in good
      agreement. The strip was stable for storage more than 5 months at 4  degrees C.
      The strip assay is a rapid and simple method for the simultaneous screening of
      imidacloprid and thiamethoxam in agricultural products.

PMID- 23158296
TI  - Preparation and evaluation of anion exchange open tubular column.
AB  - An anion open tubular column (OTC) by coating cationic latex particle onto the
      silica capillary with surface sulfonate functionalized has been prepared and
      evaluated. The performance of the OTC was observed to be superior to that of
      those prepared by the bare silica capillary without sulfonation in term of
      separation efficiency. To increase the surface area of the capillary, acid and
      base-based etching method for treating silica capillary wall was carried out and
      compared. An OTC with multiple layers was prepared by alternatively coating
      cationic and anionic latex particles aiming to further increase the column
      capacity. The anion OTC with size of 50 MUm i.d. * 1 m long demonstrated good
      separation of common inorganic anions with high efficiency (e.g. for NO(2)(-),
      its theory plate number is 11655 plate/m).

PMID- 23158297
TI  - Purity determination and uncertainty evaluation of folic acid by mass balance
      method.
AB  - Folic acid is one of the most important nutrient substances for human beings,
      especially for the pregnant women and infants. Therefore the purity determination
      of folic acid is particularly important. The mass balance method was employed to
      determine the purity of folic acid, by using the measures of high performance
      liquid chromatography (HPLC), Karl Fischer titration and other conventional
      approach. The moisture quantification of folic acid was a major problem since it
      is a thermally unstable substance and it is apt to contain crystal water.
      Therefore, a novel improved Karl Fischer method was established for accurate
      determination of the water content in folic acid, whose repeatability (RSD=2.9%)
      was significantly better than that of the original direct injection method
      (RSD=12%). The purity of folic acid certified reference material (CRM) determined
      by mass balance method was 90.9% with an expanded uncertainty of 0.35%, and the
      content of water (the major impurity) was 8.5%, with an expanded uncertainty of
      0.32%.

PMID- 23158298
TI  - Determination of perfluorocompounds in popcorn packaging by pressurised liquid
      extraction and ultra-performance liquid chromatography-tandem mass spectrometry.
AB  - The development and characterisation of a method based on reverse-phase ultra
      performance liquid chromatography (UPLC) coupled to a quadrupole-time of flight
      mass spectrometer (Q-TOF-MS) with negative electrospray ionisation (ESI) to
      determine perfluorinated compounds (PFCs) in packaging is presented in this
      paper. Analytes were quantitatively recovered from packaging with methanol in
      only one PLE cycle of 6 min at 100  degrees C. The UPLC allowed the successful
      separation of the studied PFCs in less than 4 min. The whole method presented
      good precision, with RSDs below 8%, LODs from 0.6 to 16 ng g(-1); and excellent
      recovery values, around 100% in all cases, were achieved. The PLE-UPLC-MS method
      was applied to the analysis of popcorn packaging for microwave cooking. Besides
      the most commonly studied PFCs: PFOA and PFOS, the presence of other
      perfluorocarboxylic acids (PFCAs) in popcorn packaging is evidenced in this work.

PMID- 23158299
TI  - Electrochemical response of carbon paste electrode modified with mixture of
      titanium dioxide/zirconium dioxide in the detection of heavy metals: lead and
      cadmium.
AB  - A novel carbon modified electrode was developed by incorporating titanium
      dioxide/zirconium dioxide into the graphite carbon paste electrode to detect
      heavy metals-cadmium and lead. In this work, the development of the novel
      titanium dioxide/zirconium dioxide modified carbon paste electrode was studied to
      determine the optimum synthesis conditions related to the temperature, heating
      duration, amount and ratio of titanium dioxide/zirconium dioxide, and amount of
      surfactant, to create the most reproducible results. Using cyclic voltammetric
      (CV) analysis, this study has proven that the novel titanium dioxide/zirconium
      dioxide can be utilized to detect heavy metals-lead and cadmium, at relatively
      low concentrations (7.6*10(-6) M and 1.1*10(-5) M for Pb and Cd, respectively) at
      optimum pH value (pH=3). From analyzing CV data the optimal electrodes surface
      area was estimated to be 0.028 (+/-0.003) cm(2). Also, under the specific
      experimental conditions, electron transfer coefficients were estimated to be 0.44
      and 0.33 along with the heterogeneous electron transfer rate constants of
      5.64*10(-3) and 2.42*10(-3) (cm/s) for Pb and Cd, respectively.

PMID- 23158300
TI  - A rapid colorimetric detection method of trace Cr (VI) based on the redox etching
      of Ag(core)-Au(shell) nanoparticles at room temperature.
AB  - A rapid colorimetric detection method of trace Cr (VI) in aqueous solutions has
      been developed based on non-aggregated Ag(core)-Au(shell) nanoparticles. It is
      based on the fact that Cr (VI) redox etches Ag(core)-Au(shell) nanoparticles at
      the present of bromide ions of hexadecyl trimethyl ammonium bromide (CTAB). The
      etching process of Ag(core)-Au(shell) nanoparticles would lead to a blue shift in
      the surface plasmon resonance (SPR) absorption peak as the size of Ag(core)
      Au(shell) nanoparticles decreased. This colorimetric strategy based on size and
      component dependence of core-shell nanoparticles during the etching process
      provided a highly sensitive and selective detection method toward Cr (VI).
      Compared with other detection methods, this method provided a wide linear
      detection range from 1*10(-8) M to 8*10(-6) M over one order of magnitude, also
      has some practical capability. The cost-effective probe in this colorimetric
      method allowed rapid and sensitive detection of trace Cr (VI) ions as low as
      1.0*10(-7) M based on the observations by the naked eyes and 1.0*10(-8) M based
      on the measurements of UV-vis spectra in aqueous solutions at room temperature.
      According to the preliminary data, it indicated that the current method showed
      very promising practical applicability for the determination of Cr (VI) in real
      environmental samples.

PMID- 23158301
TI  - A novel fluoride-selective electrode based on metalloporphyrin grafted
      grapheneoxide.
AB  - In this work, the unique properties of graphene oxide were combined with the
      anion selectivity of metalloporphyrin to fabricate a novel fluoride-selective
      sensor. The electrode made of 27% PVC, 54% NPOE, 4% NaTPB and 15% NbTPP-GO was
      found to show the most favorable behavior. The sensor shows a Nernstian response
      (58.3 mV decade(-1)) in the concentration window of 5.0*10(-1)-5.0*10(-7) mol L(
      1)with detection limit of 8.0*10(-87) mol L(-1). The response of the sensor was
      found to be stable in the pH range of 3.0-7.0 and the metalloporphyrin grafted-GO
      based F(-) sensors displayed very good selectivity with respect to a number of
      anions. The proposed sensor displays a long life time (more than 12 weeks) with a
      short response time of about 20 s.

PMID- 23158302
TI  - Graphene in combination with cucurbit[n]urils as electrode modifiers for
      electroanalytical biomolecules sensing.
AB  - Cucurbit[n]urils have been supported on graphene to develop sensitive and
      selective electrodes. The electrochemical response of modified electrodes
      containing graphene or graphene plus cucurbiturils has been studied for three
      probe molecules including hydroxymethylferrocene, ferrocyanide and
      methylviologen. It was found that the properties of these modified electrodes are
      derived from an increase in electron mobility and catalytic activity imparted by
      graphene and the selective complexation and molecular recognition due to
      cucurbit[n]urils. These properties of the graphene/cucurbit[n]urils modified
      electrodes have been applied for the electrochemical detection of relevant
      biomolecules as tryptophan at 0.69*10(-7) M concentration.

PMID- 23158303
TI  - Selective control of the radical-scavenging activity of poly(phenols) in aqueous
      media in terms of their electron-donor properties, using a stable organic radical
      as chemical sensor.
AB  - The tri-potassium salt of tris(2,3,5,6-tetrachloro-4
      hydroxysulphonylphenyl)methyl radical, 3K(+) TSPTM(3-), is a good chemical sensor
      of the radical-scavenging activity of poly(phenols) in aqueous media. Its water
      solubility and its stability at all pH values facilitates the study of the
      influence of the pH of the medium on the activity of poly(phenols). The radical
      scavenging activity of three flavonoids of the catechol and pyrogallol type and
      the activity of catechol, pyrogallol and methyl gallate at pH values 7 and 8
      which are close to physiological pH value (7.4) have been measured. This radical
      species reacts exclusively by an electron transfer mechanism against the reducing
      poly(phenols). Therefore, the experiments to determine the radical-scavenging
      activity of poly(phenols) with 3K(+) TSPTM(3-) are related to their ionization
      potentials (IP). As IP is a function of the pH of the medium, the electron donor
      ability of a poly(phenol) depends on the acidity or basicity of the fluid in
      question. The radical-scavenging activity of poly(phenols) 1-6 is higher at pH 8
      than at pH 7. 3K(+) TSPTM(3-) is able to discriminate between catecholic and
      pyrogallolic moieties of poly(phenols) in water solutions by taking measurements
      at different pH values. By adjusting the pH of the medium 3K(+) TSPTM(3-) will
      easily detect those moieties (e.g. pyrogallol) most prone to elicit prooxidant
      effects.

PMID- 23158304
TI  - Atmospheric pressure vapour phase decomposition: a proof of principle.
AB  - In the present work we demonstrated that the digestion of difficult matrices
      (high boiling petrochemical fractions and distillation bottoms) can be achieved
      by oxidation with nitric acid vapours at atmospheric pressure employing simple
      laboratory glassware. The application of this procedure as a digestion method
      prior to Total Reflection X-Ray Fluorescence (TXRF) is presented, although the
      employment of other detection techniques may be foreseen. The method ensured a
      fast, less than half an hour, treatment time and detection limits in the range 20
      100 MUg/kg for As, Bi, Co, Cr, Cu, Fe, Mn, Ni, Pb, Sr, Zn, whereas higher values
      were obtained for Ba, Ca, K, P, Rh, Ti and V (0.3-3 mg/kg). The potentialities
      and limitations of this procedure were discussed: the application to a broad
      range of matrices may be foreseen.

PMID- 23158305
TI  - Multiple pH-responsive graphene composites by non-covalent modification with
      chitosan.
AB  - Multiple pH-sensitive composites have been prepared through non-covalently
      functionalizing chemically converted graphene (CCG) with chitosan. Chtiosan
      exhibits as polybases and CCG shows characteristics of polyacids. Owing to the
      synergistic effects of chitosan and CCG, chitosan decorated graphene (CS-G)
      presents a multiple pH-responsive behavior that it can be dispersed well whether
      in acidic or in basic solution but aggregated in near-neutral solution. After CS
      G was modified through a controlled deposition and cross-linking process of
      chitosan, the resultant cross-linked chitosan decorated graphene (CLCS-G) can be
      converted to a different pH-sensitive material that disperses only in acidic
      solution. Both CS-G and CLCS-G present a reversible switching between dispersed
      and aggregated states with pH as a stimulus. The unique pH response mechanisms of
      CS-G and CLCS-G have been further investigated by zeta potential analysis. Based
      on the unique pH-responsive property of CS-G, a stable and repeatable pH-driven
      switch was developed for monitoring pH change.

PMID- 23158306
TI  - Calculation of equilibrium binding constants and cooperativity of Cu(II) mixed
      solvated complexes formation.
AB  - A new extension of matrix approach is proposed to calculate the equilibrium
      constants of coordinated solvent substitution in a metal ion first salvation
      shell in the mixed solvent system. The proposed method allows reducing the number
      of independent variables, necessary to calculate the fractions of species in
      solution. The equilibrium model of MeCN substitution with DMF and DMSO in the
      presence of Cu(II) ion for the assessment of structure of intermediate species is
      presented and verified. The distribution diagrams of Cu(II) species in mixed
      organic solvents have been analyzed using the modified matrix method. The
      intrinsic equilibrium constants K of the first solvent molecule replacement in
      the Cu(II) coordination shell and the correction for the mutual influence between
      the solvent molecules as ligands in the successive complex formation
      (cooperativity parameter w) in acetonitrile solution have been calculated from
      the fitting procedure. It is shown that anticooperative substitution of MeCN by
      donor ligands in the first coordination shell of the Cu(II) ion is always
      governed by the change of coordination number during the stepwise process.

PMID- 23158307
TI  - Accurate and reproducible ion mobility measurements for chemical standard
      evaluation.
AB  - Chemical standards are used to calibrate ion mobility spectrometers (IMS) for
      accurate and precise identification of target compounds. Research over the past
      30 years has identified several positive and negative mode compounds that have
      been used as IMS standards. However, the IMS research community has not come to a
      consensus on any chemical compound(s) for use as a reference standard. Also, the
      reported K(0) values for the same compound analyzed on several IMS systems can be
      inconsistent. In many cases, mobility has not been correlated with a mass
      identification of an ion. The primary goal of this work was to provide mass
      identified mobility (K(0)) values for standards. The results of this work were
      mass-identified K(0) values for positive and negative mode IMS chemical
      standards. The negative mode results of this study showed that TNT is a viable
      negative mode reference standard. New temperature-dependent K(0) values were
      found by characterizing drift gas temperature and water content; several examples
      were found of temperature-dependent changes for the ion species of several
      standards. The overall recommendation of this study is that proposed IMS
      standards should have temperature-dependent K(0) values quoted in the literature
      instead of using a single K(0) value for a compound.

PMID- 23158308
TI  - A highly sensitive and selective bulk optode based on benzimidazol derivative as
      an ionophore and ETH5294 for the determination of ultra trace amount of silver
      ions.
AB  - A novel optical chemical sensor (optode) was fabricated for the determination of
      silver ions. The optical sensor was prepared by incorporating recently
      synthesized ionophore, 7-(1H-benzimidazol-1-ylmethyl)-5,6,7,8,9,10-hexahydro-2H
      1,13,4,7,10-benzodioxatriaza cyclopentadecine-3,11(4H,12H)-dione, sodium
      tetraphenyl borate (NaTPB) as an anionic additive, 3-octadecanoylimino-7
      (diethylamino)-1,2-benzophenoxazine (ETH5294) as a chromoionophore, and dioctyl
      phthalate (DOP) as a plasticizer in a poly(vinyl chloride) membrane. The effect
      of several parameters in determining Ag(+) was studied and optimized. The
      spectrophotometric method (lambda(max) of 660 nm) was used for the determination
      of Ag(+). Under the optimum conditions, the optical sensor has a wide dynamic
      range of 1.02*10(-11) to 8.94*10(-5) mol L(-1) Ag(+) with the detection limit as
      low as 2.8*10(-12) mol L(-1). The response time of the sensor was ~150 s, with a
      RSD% of 0.4% (for 1.0*10(-6) mol L(-1), n=7). The optode could be regenerated by
      0.2 mol L(-1) HCl solution. The interferences of potential interfering ions were
      studied. It was shown that the new optode was very selective to silver ions and
      had no significant response to common ions such as Mn(2+), Cd(2+), Ni(2+),
      Hg(2+), and Co(2+). It can be claimed that the sensor can specifically detect
      silver ions. The sensor was successfully applied for the determination of silver
      ions in different real samples.

PMID- 23158309
TI  - Development and validation of automatic HS-SPME with a gas chromatography-ion
      trap/mass spectrometry method for analysis of volatiles in wines.
AB  - An automated headspace solid-phase microextraction (HS-SPME) combined with gas
      chromatography-ion trap/mass spectrometry (GC-IT/MS) was developed in order to
      quantify a large number of volatile compounds in wines such as alcohols, ester,
      norisoprenoids and terpenes. The procedures were optimized for SPME fiber
      selection, pre-incubation temperature and time, extraction temperature and time,
      and salt addition. A central composite experimental design was used in the
      optimization of the extraction conditions. The volatile compounds showed optimal
      extraction using a DVB/CAR/PDMS fiber, incubation of 5 ml of wine with 2g NaCl at
      45  degrees C during 5 min, and subsequent extraction of 30 min at the same
      temperature. The method allowed the identification of 64 volatile compounds.
      Afterwards, the method was validated successfully for the most significant
      compounds and was applied to study the volatile composition of different white
      wines.

PMID- 23158310
TI  - Chemical analysis of ZnGeP2 as a new line of research of heterogeneity in bulk
      crystals.
AB  - Chemical analysis coupled with the inductively coupled plasma atomic emission
      spectroscopy is proposed as a suitable method for determination of the phase
      heterogeneity of bulk ZnGeP(2) crystals, which are excellent materials for non
      linear infrared technique. The crystal phase heterogeneity is resulting from
      impurity phases ZnP(2) or Ge, which are undetectable by traditional x-ray
      diffraction method because of their low content. The precise analytical procedure
      was developed using a well characterized homogeneous ZnGeP(2) crystal as a
      standard reference material to analyze a series of bulk ZnGeP(2) crystals with a
      low content of ZnP(2) or Ge. In this case, all static (instrumental and
      methodical) errors of the analysis were corrected, and dispersion of the
      analytical results (random errors) for crystals tested was related to a spatial
      variation of the impurity phase content and its irregular distribution. The
      spread of the analytical results found for 15 independent weights of each test
      crystal is demonstrated graphically.

PMID- 23158311
TI  - Fluorescence resonance energy transfer quenching at the surface of graphene
      quantum dots for ultrasensitive detection of TNT.
AB  - This paper for the first time reports a chemical method to prepare graphene
      quantum dots (GQDs) from GO. Water soluble and surface unmodified GQDs, serving
      as a novel, effective and simple fluorescent sensing platform for ultrasensitive
      detection of 2,4,6-trinitrotoluene (TNT) in solution by fluorescence resonance
      energy transfer (FRET) quenching. The fluorescent GQDs can specifically bind TNT
      species by the pi-pi stacking interaction between GQDs and aromatic rings. The
      resultant TNT bound at the GQDs surface can strongly suppress the fluorescence
      emission by the FRET from GQDs donor to the irradiative TNT acceptor through
      intermolecular polar-polar interactions at spatial proximity. The unmodified GQDs
      can sensitively detect down to ~0.495 ppm (2.2 MUM) TNT with the use of only 1 mL
      of GQDs solution. The simple FRET-based GQDs reported here exhibit high and
      stable fluorescence. Eliminating further treatment or modification, this method
      simplifies and shortens the experimental process. It possesses good assembly
      flexibility and can thus find many applications in the detection of ultratrace
      analytes.

PMID- 23158312
TI  - Analysis of the volatile components emitted from cut tobacco processing by gas
      chromatography/mass spectrometry thermal desorption system.
AB  - A sensitive and reliable method was developed for the determination of volatile
      components emitted from cut tobacco processing using thermal desorption (TD)
      followed by gas chromatography-mass spectrometry (GC-MS). In the work, to obtain
      the optimal sorbent, three commercial sorbents were compared in terms of
      adsorption efficiency. The carbotrap 349 was found to have the best performance.
      The desorption conditions were also studied. Validation of the TD-GC-MS method
      showed good sensibility, linearity and precision. Limits of detection ranges were
      from 0.20 to 3.6 ng. Calibration curves were obtained by plotting peak area
      versus concentration and the correlation coefficients relating to linearity were
      at least 0.9984. The analysis was reproducible, with relative standard deviation
      (n=8) within 6.5%. The target compound breakthrough examination showed no
      significant losses when about 1500 ng standards were prepared. In order to
      evaluate the performance of the analytical method in the volatile constituents of
      cut tobacco, samples were taken in industrial areas of cut tobacco processing.
      Recoveries ranged from 85.1% to 110% for all the compounds and good precision had
      been reached (RSD<13.3). The results proved that TD-GC-MS was a simple, rapid and
      accurate method for the analysis of volatile compounds emitted from cut tobacco
      drying step.

PMID- 23158313
TI  - Determination of Zn-citrate in human milk by CIM monolithic chromatography with
      atomic and mass spectrometry detection.
AB  - In human milk zinc (Zn) is bound to proteins and low molecular mass (LMM)
      ligands. Numerous investigations demonstrated that Zn bioavailability in human
      milk is for infant much higher than in cow's milk. It was presumed that in the
      LMM human milk fraction highly bioavailable Zn-citrate prevails. However,
      literature data are controversial regarding the amount of Zn-citrate in human
      milk since analytical procedures reported were not quantitative. So, complex
      investigation was carried out to develop analytical method for quantitative
      determination of this biologically important molecule. Studies were performed
      within the pH range 5-7 by the use of synthetic solutions of Zn-citrate prepared
      in HEPES, MOPS and MES buffers. Zn-citrate was separated on weak anion-exchange
      convective interaction media (CIM) diethylaminoethyl (DEAE) monolithic
      chromatographic column using NH(4)NO(3) as an eluent. Separated Zn species were
      determined by flame atomic absorption spectrometry (FAAS) or inductively coupled
      plasma mass spectrometry (ICP-MS). Quantitative separation of Zn-citrate
      complexes ([Zn(Cit)](-) and [Zn(Cit)(2)](4-); column recoveries 94-102%) and good
      repeatability and reproducibility of results with relative standard deviation
      (RSD+/-3.0%) were obtained. In fractions under the chromatographic peaks Zn
      binding ligand was identified by electrospray ionization tandem mass spectrometry
      (ESI-MS-MS). Limits of detection (LOD) for determination of Zn-citrate species by
      CIM DEAE-FAAS and CIM DEAE-ICP-MS were 0.01 MUg Zn mL(-1) and 0.0005 MUg Zn mL(
      1), respectively. Both techniques were sensitive enough for quantification of Zn
      citrate in human milk. Results demonstrated that about 23% of total Zn was
      present in the LMM milk fraction and that LMM-Zn corresponded to Zn-citrate. The
      developed speciation method represents a reliable analytical tool for
      investigation of the percentage and the amount of Zn-citrate in human milk.

PMID- 23158314
TI  - A comparative study of solid and liquid inner contact benzalkonium chloride ion
      selective electrode membranes.
AB  - A comparative study was made between two designs of benzalkonium ion (Bz)
      selective electrodes: a silver-coated (solid contact) called electrode A and a
      PVC membrane (liquid inner contact) called electrode B based on benzalkonium
      phosphomolybdate (Bz-PM) as ion-exchanger complex. Electrode A has a linear
      dynamic range from 2.0*10(-8) to 1.0*10(-2) mol L(-1), with a Nernstian slope of
      60+/-0.3 mV/decade and a detection limit of 2.0*10(-8) mol L(-1). Electrode B
      shows linearity over the concentration range from 2.0*10(-7) to 1.0*10(-2) mol L(
      1), with a Nernstian slope of 55+/-1.2 mV/decade and a limit of detection of
      1.5*10(-7) mol L(-1). Electrode A showed better performance than electrode B. The
      detection limit of benzalkonium chloride (BzCl) was effectively improved by a
      solid contact ion-selective electrode (SC-ISE), rather than the traditional
      liquid inner contact electrode that gives lower detection limits because of
      diminished ion fluxes. The present electrodes show clear discrimination of BzCl
      from several inorganic, organic ions, sugars and some common drug excipients. The
      sensors were applied efficiently for determination of BzCl in its pharmaceutical
      preparations (eye, ear and nasal drops) using standard addition and the
      calibration curve methods.

PMID- 23158315
TI  - Quantification of terbinafine in pharmaceutical tablets using capillary
      electrophoresis with contactless conductivity detection and batch injection
      analysis with amperometric detection.
AB  - Terbinafine hydrochloride (TerbHCl) is an allylamine derivative with fungicidal
      action, especially against dermatophytes. Different analytical methods have been
      reported for quantifying TerbHCl in different samples. These procedures require
      time-consuming sample preparation or expensive instrumentation. In this paper,
      electrochemical methods involving capillary electrophoresis with contactless
      conductivity detection, and amperometry associated with batch injection analysis,
      are described for the determination of TerbHCl in pharmaceutical products. In the
      capillary electrophoresis experiments, terbinafine was protonated and analyzed in
      the cationic form in less than 1 min. A linear range from 1.46 to 36.4 MUg mL(-1)
      in acetate buffer solution and a detection limit of 0.11 MUg mL(-1) were
      achieved. In the amperometric studies, terbinafine was oxidized at +0.85 V with
      high throughput (225 injection h(-1)) and good linear range (10-100 MUmol L(-1)).
      It was also possible to determine the antifungal agent using simultaneous
      conductometric and potentiometric titrations in the presence of 5% ethanol. The
      electrochemical methods were applied to the quantification of TerbHCl in
      different tablet samples; the results were comparable with values indicated by
      the manufacturer and those found using titrimetry according to the Pharmacopoeia.
      The electrochemical methods are simple, rapid and an appropriate alternative for
      quantifying this drug in real samples.

PMID- 23158316
TI  - Label-free impedimetric immunosensor for sensitive detection of 2,4
      dichlorophenoxybutyric acid (2,4-DB) in soybean.
AB  - Electrochemical impedance immunosensor, with its high sensitivity from
      electrochemical impedance analysis and ideal specificity from the immunoassay, is
      increasingly used in the detection of a kind of phenoxy acid herbicides which is
      2,4-Dichlorophenoxybutyric acid (2,4-DB). In this experiment, synthetic 2,4-DB
      antibodies were immobilized on the electrode by the crosslinking of L
      Cysteine/glutaraldehyde, and 2,4-DB were measured by the increase of electron
      transfer resistance when the immune reaction occurred, with Fe(CN)(6)(3
      )/Fe(CN)(6)(4-) as the probe. Under optimal conditions, the change of resistance
      is in a linear relationship with the logarithm of the concentration in the range
      of 1.0*10(-7)-1.0*10(-3) g/L (R=0.994) with the detection limit of 1.0*10(-7) g/L
      (0.1 ppb). This method bears such merits as simplicity in operation, high
      sensitivity, wide linear range, specificity, reproducibility and good stability.
      The actual soybean samples were analyzed with the recovery of 82.8%-102.3%.

PMID- 23158317
TI  - Sequential injection spectrophotometric system for evaluation of mushroom
      tyrosinase-inhibitory activity.
AB  - A sequential injection (SI) spectrophotometric method with absorbance detection
      at 475 nm has been developed for evaluating activity of some compounds on an
      inhibition of the mushroom tyrosinase. The method involved a reaction of 3,4
      dihydroxyphenylalanine (L-DOPA) and mushroom tyrosinase to form the o
      dopaquinone. The decrease of the o-dopaquinone was related to an increase of
      tyrosinase-inhibitory activity. Under the optimum conditions (concentration and
      volume of L-DOPA and mushroom tyrosinase of 2.0 mM, 60 MUL and 142 U mL(-1), 15
      MUL, respectively), some antioxidant compounds were examined for the tyrosinase
      inhibitory activity. A batch enzymatic assay of tyrosinase-inhibitory activity
      was applied as the reference method for comparison. The results of IC(50) values
      obtained from the proposed method and the batch method were correlated well, with
      r(2) of 0.969. The SIA provides higher precision and degrees of automation,
      consumes smaller amounts of chemicals and it is simpler and faster than the batch
      method.

PMID- 23158318
TI  - A novel assay to evaluate promoting effects of proteins on calcium oxalate
      crystal invasion through extracellular matrix based on plasminogen/plasmin
      activity.
AB  - One of the important processes in kidney stone development is crystal invasion
      through extracellular matrix (ECM). Some proteins in renal tissue or urine have
      been thought to aggravate crystal invasion. However, this pathogenic mechanism
      has been previously under-investigated due to a lack of crystal invasion assay.
      In the present study, we have developed a novel assay for the investigations of
      calcium oxalate monohydrate (COM) crystal invasion. Matrix gel was loaded into an
      in-house migration chamber made on a glass slide to simulate the ECM environment.
      COM crystals were coated with the tested protein, which was then bound with
      plasminogen. The crystal-protein-(plasminogen) complex and urokinase plasminogen
      activator (uPA) were placed on-top of the matrix gel. If the tested protein had
      plasminogen-binding capability, the remaining plasminogen would be activated by
      uPA to plasmin, which caused crystal migration through the matrix gel. We then
      applied this novel assay to evaluate effects of some abundant kidney/urine
      proteins (including purified albumin, carbonic anhydrase, lysozyme and Tamm
      Horsfall protein) on COM crystal invasion. The data revealed that albumin, which
      is the known plasminogen-binding protein, dramatically induced plasmin activity
      and crystal invasion, whereas other proteins had no significant effects as
      compared to the control. In summary, we have successfully developed a novel assay
      for the investigations of crystal invasion based on the plasminogen/plasmin
      system. This assay is applicable to examine proteins that may serve as potential
      aggravators of crystal invasion and thus will be very useful for further studies
      on kidney stone development.

PMID- 23158319
TI  - Pseudo-indicator behaviour of platinum electrode explored for the potentiometric
      estimation of non-redox systems.
AB  - A pseudo-indicator electrode based potentiometric method for estimation of non
      redox metal ions is presented. In the proposed method, nature and concentration
      specific impact of analyte over the redox potential of ideally polarisable
      Pt/pregenerated-redox-couple interface forms the basis of quantification. Utility
      of the method in estimation of six non-redox metal ions viz. Zn(2+), Cu(2+),
      Ni(2+), Cd(2+), Pb(2+), Al(3+) in the concentration range of 10(-1)-10(-3) moldm(
      3), individually and as binary mixtures is also presented. Three types of
      potentiometric behaviours, which we ascribe to the nature specific thermodynamic
      and kinetic aspects of metal-EDTA binding, were observed. While Cu(2+), Ni(2+),
      Pb(2+) and Al(3+) were found to bind EDTA efficiently, without exchanging Fe(3+);
      Zn(2+) and Cd(2+) were observed to replace Fe(3+) from EDTA. In contrast, Ca(2+)
      and Mg(2+) were found to show no binding affinity to EDTA in the pH range
      employed in the present work. The proposed method was also used to explore the
      reversibility and the Nernestian behaviour of ferricyanide/ferrocyanide redox
      couple through spectroelectrochemical titration of Zn(2+) with ferrocyanide. The
      presented method is presaged to be a reliable and low cost future replacement for
      costly and delicate ion selective electrodes (ISE) in the estimation of non-redox
      species like Zn(2+), Cu(2+), etc.

PMID- 23158320
TI  - Prediction models for Arabica coffee beverage quality based on aroma analyses and
      chemometrics.
AB  - In this work, soft modeling based on chemometric analyses of coffee beverage
      sensory data and the chromatographic profiles of volatile roasted coffee
      compounds is proposed to predict the scores of acidity, bitterness, flavor,
      cleanliness, body, and overall quality of the coffee beverage. A partial least
      squares (PLS) regression method was used to construct the models. The ordered
      predictor selection (OPS) algorithm was applied to select the compounds for the
      regression model of each sensory attribute in order to take only significant
      chromatographic peaks into account. The prediction errors of these models, using
      4 or 5 latent variables, were equal to 0.28, 0.33, 0.35, 0.33, 0.34 and 0.41, for
      each of the attributes and compatible with the errors of the mean scores of the
      experts. Thus, the results proved the feasibility of using a similar methodology
      in on-line or routine applications to predict the sensory quality of Brazilian
      Arabica coffee.

PMID- 23158321
TI  - Synthesis and characterization of a high selective mercury(II)-imprinted polymer
      using novel aminothiol monomer.
AB  - A novel aminothiol monomer was synthesized from' 2-mercaptoethylamine for
      complexing the Hg(II) ion. The synthesized complex monomer has been used for
      preparing the Hg(II)-imprinted polymer by radical copolymerization with
      methacrylic acid and ethylene glycol dimethacrylate and AIBN as the functional
      monomer, cross-linker and initiator respectively in the presence of a binary
      porogen of DMSO and toluene. The results of batch procedures showed that the
      Hg(II)-imprinted polymer has adsorption capacity of 28 mg g(-1). The distribution
      ratio (K(d)) values of the Hg(II)-imprinted polymer increases for mercury with
      respect to both K(d) values of CH(3)Hg(I), Zn(II), Cd(II) and non-imprinted
      polymers. The relative selective factors k for Hg(II)/ CH(3)Hg(I), Hg(II)/Cd(II)
      and Hg(II)/Zn(II) are 15.5, 12.5, and 20.6, which are greater than 1. The thermal
      stability has also been investigated by thermogravimetric analysis which shows
      that the polymerization process increases the thermal stability up to 125 
      degrees C.

PMID- 23158322
TI  - Calcein and calcein-Ag films under vapor exposure: sensing properties and
      reversible film restructuring.
AB  - We studied the adsorption properties of organic and organic-inorganic films based
      on the dye calcein. Embedding of silver nanoparticles increases film sensitivity
      to some analytes (in particular, sensitivity to ethanol increases by about 30%).
      Both films demonstrate high sensitivity to water vapor, response of about 7000 Hz
      for a quartz crystal microbalance sensor. Our investigations showed that
      essential restructuring of films and increase in their thickness occurs in the
      course of adsorption of water molecules. These changes are reversible: after
      drying, the sensor response reverts to zero and the film structure is fully
      restored. The value and reversibility of changes occurring because of adsorption
      processes at the surfaces of calcein and calcein-Ag films make these materials
      very promising for application not only in sensorics but also when developing
      nanoactuators as well.

PMID- 23158323
TI  - Trace analysis of sulfonylurea herbicides in water samples by solid-phase
      extraction and liquid chromatography-tandem mass spectrometry.
AB  - A sensitive method for the simultaneous determination of 30 sulfonylurea
      herbicides in tap and leaching waters has been developed. Liquid chromatography
      tandem-mass spectrometry (LC-MS(2)) in electrospray ionization positive mode was
      used for the separation, identification and quantification of these compounds.
      The procedure involves a preconcentration step based on solid-phase extraction
      with a silica-based bonded C(18) cartridge (Sep-Pak Plus) and a N-vinyl
      pyrrolidone polymer cartridge (Oasis HLB). The best results were obtained with
      Oasis HLB using methanol as elution solvent. Average recoveries of 30 analytes
      from water samples were in the range of 79-115% with a relative standard
      deviation of <6.1%. The limits of quantification (LOQs) obtained in tap and
      leaching water samples were in the range of 0.1-5.9 and 0.4-5.8 ng L(-1),
      respectively. The proposed method was used to determine sulfonylurea herbicide
      levels in leaching water samples taken from three lysimeters located in an
      experimental greenhouse.

PMID- 23158324
TI  - Use of pressurized hot water extraction and high performance liquid
      chromatography-inductively coupled plasma-mass spectrometry for water soluble
      halides speciation in atmospheric particulate matter.
AB  - The feasibility of pressurized hot water extraction (PHWE) has been novelty
      investigated to speed up water soluble halide species (bromide, Br(-); bromate,
      BrO(3)(-); iodide, I(-) and iodate, IO(3)(-)) leaching from atmospheric
      particulate matter (PM(10) and PM(2.5)). Total bromine and iodine and total water
      soluble bromine and iodine have been assessed by inductively coupled plasma-mass
      spectrometry (ICP-MS). Water-soluble bromine and iodine species were also
      measured by ICP-MS after anion exchange high performance liquid chromatography
      (HPLC). Variables inherent to the pressurized hot water extraction process
      (temperature, modifier concentration, static time, pressure, number of cycles and
      dispersing agent mass) were fully studied. Results showed that the pressurized
      leaching procedure can be performed in 9 min (5 min for pre-heating, 2 min of
      static time, 1 min of purge time, and 1 min of end relief time). The use of
      diluted acetic acid as a modifier did not improve the target recoveries.
      Dispersing agent (diatomaceous earth) was not needed, which reduces the time for
      filling the cells. Water-soluble halides were reached under the following
      extraction conditions: extraction temperature of 100  degrees C, pressure of 1500
      psi, static time of 2 min and 1 extraction cycle. Optimized HPLC conditions
      consisted of an isocratic elution with 175 mM ammonium nitrate plus 15% (v/v)
      methanol as mobile phase (optimum flow rate of at 1.5 mL min(-1)). Analytical
      performances, such as limits of detection and quantification, repeatability and
      analytical recoveries of the over-all procedure have been established. Results
      obtained show water soluble halides accounted for approximately 20.9+/-1.3 and
      11.8+/-0.6% of the total bromine and total iodine, respectively. A 79 and 89% of
      bromine and iodine was non-water soluble, which may be organic non-water soluble
      species. Br(-) and IO(3)(-) were found to be the major species, and they
      accounted for 100% of the total water-soluble bromine and iodine.

PMID- 23158325
TI  - Comparison of extraction methods for exploitation of grape skin residues from
      ethanol distillation.
AB  - Four extraction techniques-namely, conventional maceration, ultrasound-assisted
      extraction, microwave-assisted extraction, and superheated liquid extraction
      (SHLE)-have been compared to evaluate their suitability to obtain valuable
      compounds from a raw material traditionally of scant interest: grape skin
      residues from ethanol-distillation. With this aim, red- and white-grape skins
      were separated from the rest of the pomace residue and subjected to extraction
      with 1:1 ethanol-acidic water as extractant in order to obtain the largest
      possible number of valuable compounds from this material, which has so far been
      used only as a heat source. The resulting extracts were characterized by the
      Folin-Ciocalteu and Ferric Reducing Antioxidant Power tests and by liquid
      chromatography-time-of-flight/mass spectrometry (LC-TOF/MS). The composition of
      the extracts under each of the optimal conditions was studied by LC-TOF/MS, and
      the information thus obtained compared by Venn diagrams. These diagrams, together
      with the extracted base peak chromatograms, were used to assess the optimal
      working conditions. Tentative identification of compounds was conducted using
      open-free databases. Grape skins from distillation industries are a source of
      compounds of interest for the food and nutraceutical fields.

PMID- 23158326
TI  - Rapid sample pre-treatment prior to GC-MS and GC-MS/MS urinary toxicological
      screening.
AB  - Drug screening is an important issue in clinical and forensic toxicology. Gas
      chromatography coupled to mass spectrometry (GC-MS) remains the gold standard
      technique for the screening of unknown compounds in urine samples. However, this
      technique requires substantial sample preparation, which is time consuming.
      Moreover, some common drugs such as cannabis cannot be easily detected in urine
      using general procedures. In this work, a sample preparation protocol for
      treating 200 MUL of urine in less than 30 min is described. The enzymatic
      hydrolysis of glucuro-conjugates was performed in 5 min thanks to the use of
      microwaves. The use of a deconvolution software allowed reducing the GC-MS run to
      10 min, without impairing the quality of the compound identifications. Comparing
      the results from 139 authentic urine samples to those obtained using the current
      routine analysis indicated this method performed well. Moreover, additional 5-min
      GC-MS/MS programs are described, enabling a very sensitive target screening of 54
      drugs, including THC-COOH or buprenorphine, without further sample preparation.
      These methods appeared as an interesting alternative to immuno-assays based
      screening. The analytical strategy presented in this article proved to be a
      promising approach for systematic toxicological analysis (STA) of drugs in urine.

PMID- 23158327
TI  - A preconcentrator chip employing MU-SPME array coated with in-situ-synthesized
      carbon adsorbent film for VOCs analysis.
AB  - We report the design, fabrication, and evaluation of a MU-preconcentrator chip
      that utilizes an array of solid-phase microextraction (SPME) needles coated with
      in-situ-grown carbon adsorbent film. The structure of the SPME needle
      (diameter=100 MUm, height=250 MUm) array inside the sampling chamber was
      fabricated using a deep reactive-ion etching (DRIE) process to enhance the
      attachable surface area for adsorbent film. Heaters and temperature sensors were
      fabricated onto the back of a MU-preconcentrator chip using lithography
      patterning and a metal lift-off process. The devices were sealed by anodic
      bonding and diced prior to the application of the adsorbent film. An adsorbent
      precursor, cellulose was dissolved in water and dynamically coated onto the SPME
      needle array. The coated cellulose film was converted into a porous carbon film
      via pyrolysis at 600  degrees C in a N(2) atmosphere. The surface area of the
      carbon adsorbent film was 308 m(2)/g, which is higher than that of a commercial
      adsorbent Carbopack X. A preconcentration factor as high as 13,637-fold was
      demonstrated using toluene. Eleven volatile organic compounds (VOCs) of different
      volatilities and functional groups were sampled and analyzed by GC-FID, and the
      desorption peak widths at half height were all less than 2.6 s after elution from
      a 15m capillary GC column. There was no sign of performance degradation after
      continuous operation for 50 cycles in air.

PMID- 23158328
TI  - A novel needle trap device with single wall carbon nanotubes sol-gel sorbent
      packed for sampling and analysis of volatile organohalogen compounds in air.
AB  - This paper describes a new approach that combines needle trap devices (NTDs) with
      a newly synthesized silanated nano material as sorbent for sampling and analysis
      of HVOCs in air. The sol-gel technique was used for preparation of the single
      wall carbon nanotube (SWCNT)/silica composite as sorbent, packed inside a 21
      gauge NTD. Application of this method as an exhaustive sampler device was
      investigated under different laboratory conditions in this study. Predetermined
      concentrations of each analyte were prepared in a home-made standard chamber, and
      the effects of experimental parameters, such as temperature, humidity, sampling
      air flow rate, breakthrough volume and storage time on NTD, and the sorbent
      performance were investigated. The proposed NTD was used in two different modes
      and two different injection methods, and an NTD with a side hole, a narrow neck
      glass liner and syringe pump assisted injection of carrier gas were applied. The
      NTD packed with SWCNTs/silica composite was compared to the NTD packed with PDMS
      and also SPME with CAR/PDMS. For four compounds, LOD was 0.001-0.01 ng mL(-1),
      LOQ was 0.007-0.03 ng mL(-1), and the relative standard division for
      repeatability of method was 2.5-6.7%. The results show that the incorporation of
      NTD and SWCNTs/silica composite is a reliable and effective approach for the
      sampling and analysis of HVOCs in air. Coupling this system to GC-MS make it more
      sensitive and powerful technique.

PMID- 23158329
TI  - A rapid, environmentally friendly, and reliable method for pesticide analysis in
      high-fat samples.
AB  - This report describes the development and validation of a simple, rapid, and
      efficient method in which solid-phase extraction followed by analysis in a gas
      chromatograph equipped with an electron capture detector (SPE-GC-ECD) is used for
      the simultaneous determination of dicofol, dieldrin, endosulfan, and permethrin
      in rat adipose tissue. This study targeted pesticides for which controversies
      exist regarding the harm that they may cause to humans, such as endocrine
      disruption or cancer, and that have also been found in recent years in vegetables
      consumed by the Brazilian population. The analytical procedure was optimised for
      SPE extraction and for GC-ECD conditions. The optimised method includes the
      extraction of the samples with n-hexane followed by an SPE procedure in which
      deactivated neutral alumina cartridges are used as the sorbent and a mixture of n
      hexane:dichloromethane is used for elution. Recovery studies with spiked samples
      were used to evaluate the method's efficiency. Mean recoveries ranged from 75% to
      119% with relative standard deviations (RSD)<19%. Quantification limits (LOQs)
      were 0.05 mg kg(-1) for dieldrin and endosulfan and 0.5 mg kg(-1) for dicofol and
      permethrin. The matrix effect was pronounced for all of the pesticides studied
      and ranged from 26% to 49%. In comparison to other related methods, this method
      requires less time and solvent and allows for rapid isolation of the target
      analytes with high selectivity. This method therefore allows for the screening of
      numerous samples and can also be used for routine analyses.

PMID- 23158330
TI  - Four-way modeling of 4.2 K time-resolved excitation emission fluorescence data
      for the quantitation of polycyclic aromatic hydrocarbons in soil samples.
AB  - A screening method for the soil analysis of 15 Environmental Protection Agency
      polycyclic aromatic hydrocarbons (EPA-PAHs) is reported. The new method is based
      on the collection of 4.2 K fluorescence time-resolved excitation-emission cubes
      (TREECs) via laser-excited time-resolved Shpol'skii spectroscopy. 4.2 K
      fluorescence TREECs result from the superposition of fluorescence time-resolved
      excitation emission matrices recorded at different time windows from the laser
      excitation pulse. Potential interference from unknown sample concomitants is
      handled by processing the four-way 4.2 K fluorescence TREEC data arrays with
      either parallel factor analysis (PARAFAC) or unfolded partial least
      squares/residual-trilinearization(U-PLS/RTL). The sensitivity of the two
      approaches makes possible to determine PAHs at the ng g(-1) to pg g(-1)
      concentration level with no need for sample pre-concentration. Its selectivity
      eliminates sample clean-up steps and chromatographic separation. These features
      reduce PAH loss, analysis time and cost. The method is environmentally friendly
      as the complete screening of the 15 EPA-PAHs takes only 250 MUL of organic
      solvent per sample.

PMID- 23158331
TI  - Using a novel sol-gel stir bar sorptive extraction method for the analysis of
      steroid hormones in water by laser diode thermal desorption/atmospheric chemical
      ionization tandem mass spectrometry.
AB  - A new coating material was used for a stir bar sorptive extraction (SBSE) method
      coupled to a high throughput sample analysis technique. This allowed for a simple
      procedure for fast determinations of eight steroid hormones (estriol, estradiol,
      ethynylestradiol, estrone, progesterone, medroxyprogesterone, levonorgestrel,
      northindrone) in water. Sample pre-treatment was performed using an in-house SBSE
      method based on a polydimethylsiloxane/phenyltrimethylsiloxane/beta-cyclodextrin
      sol-gel material. The analytes were desorbed by liquid extraction prior to their
      analysis by laser diode thermal desorption/atmospheric pressure chemical
      ionization coupled to tandem mass spectrometry (LDTD-APCI-MS/MS). Several
      parameters, including ionic strength, volume and time of extraction as well as
      volume and time of desorption, were investigated to maximize extraction
      efficiency by SBSE in aqueous solutions. The in-house stir bar showed good
      reproducibility and could be used for at least 50 extractions without affecting
      analytical performance. The recoveries of the spiked steroid hormones ranged from
      55% to 96% in all water matrices studied (HPLC grade water, tap water and raw
      wastewater). Only one compound showed poor recovery values (<2% for estriol) in
      all matrices. The method detection limits (MDLs) in real matrices were within the
      range of 0.1-0.3 MUg L(-1) except for estriol at 48 MUg L(-1). The extraction
      performance of the in-house SBSE for the eight selected hormones was also
      compared with that of a commercially-available stir bar coated with
      polydimethylsiloxane (PDMS). This novel stir bar coating could prove to be useful
      method for the detection and quantification of trace levels of steroid hormones.

PMID- 23158332
TI  - Microwave digestion for the quantification of inorganic elements in coal and coal
      ash using ICP-OES.
AB  - In this paper, microwave digestion conditions have been optimised to achieve
      complete recoveries for the ash-forming inorganic elements in coal and coal
      combustion fly ash, during the analysis by inductively coupled plasma optical
      emission spectroscopy (ICP-OES). The elements analysed include six major (Al, Ca,
      Fe, K, Mg and Na) and twelve trace (As, Ba, Be, Co, Cr, Cu, Li, Mn, Ni, Pb, Sr
      and V). Seven reference samples have been tested, including two standard coal
      references, SRM1632c and SARM19, their corresponding high-temperature ashes
      (HTAs), and three coal fly ash references, SRM1633c, SRM2690 and BCR38. The
      recoveries of individual elements in these samples have been examined
      intensively, as a function of the amount of hydrofluoric acid (HF, 0-2.0 ml),
      microwave power (900 W vs. 1200 W) and sample mass (0.05 g vs. 0.1 g). As have
      been confirmed, the recoveries of these individual elements varied significantly
      with the microwave digestion condition, elemental type and sample property. For
      the coal references and their HTAs, the use of HF can be ruled out for most of
      the elements, except K associated with feldspar, Pb and V. In particular, the
      recovery of Pb in coal is highly sample-specific and thus unpredictable. The
      majority of elements in fly ash references require the use of 0.1-0.2 ml HF for a
      complete recovery. Al in fly ash is the only exceptional element which gave
      incomplete recoveries throughout, suggesting the use of a complementary technique
      for its quantification. As has proven to be the only element inconsequential of
      sample type and digestion conditions, achieving complete recoveries for all
      cases. On the power parameter, using a higher power such as 1200 W is critical,
      which has proved to be an ultimatum for the recovery of certain elements,
      especially in fly ash. Halving sample mass from 0.1 g to 0.05 g was also found to
      be insignificant.

PMID- 23158333
TI  - Method development for Cd and Hg determination in biodiesel by electrothermal
      atomic absorption spectrometry with emulsion sample introduction.
AB  - A novel method for analysis of biodiesel by electrothermal atomic absorption
      spectrometry is described. This analytical strategy involves sample preparation
      as emulsions for routine and reliable determination of Cd and Hg. Several
      experimental conditions were investigated, including emulsion stability and
      composition, furnace temperature program and matrix modification. Different
      calibration strategies were also evaluated, being the analyte addition method
      preferred both for Cd and Hg. The accuracy was verified through comparison with
      an acid digestion in a microwave closed system. The injection repeatability was
      evaluated as the average relative standard deviation (R.S.D %) for five
      successive firings and was better than 4.4% for Cd and 5.4% Hg respectively. The
      detection limits, evaluated by the 3sigma concept of calculation (n=10), were of
      10.2 MUg kg(-1) (0.9 MUg L(-1)) for Hg and 0.3 MUg kg(-1) (0.04 MUg L(-1)) for
      Cd. This method was successfully applied to the determination of Cd and Hg in
      biodiesel samples obtained from local vendors.

PMID- 23158334
TI  - A novel exonuclease III-aided amplification assay for lysozyme based on graphene
      oxide platform.
AB  - Based on exonuclease III (Exo III) aided amplification and graphene oxide (GO)
      platform for fluorescence quenching, a novel, turn-on fluorescent aptasensor for
      lysozyme (Lys) protein was constructed. The system contains a hairpin probe (HP)
      and a signal probe (SP) labeled with carboxyfluorescein (FAM) at its 5' end. HP,
      which consists of the aptamer sequence of Lys, is partially complementary to SP.
      Lys could bind with the aptamer region of the HP and facilitate the opening of
      the hairpin structure of HP, exposing a single-stranded sequence to hybridize
      with SP. This triggered the Exo III aided amplification and caused the
      degradation of SP, which liberated the free fluorophore labels. Upon the addition
      of GO, the released fluorophore could not be adsorbed and no fluorescence
      quenching occured, while the intact SPs could be adsorbed on GO surface with the
      fluorescence substantially quenched. The results revealed that the proposed
      method displayed fluorescence responses in a linear correlation to the
      concentrations of Lys within the range from 0.125 MUg/ml to 1 MUg/ml and the
      detection limit is 0.08 MUg/ml. Besides such sensitivity, the proposed strategy
      is also low-cost and simple due to its homogeneous and fluorescence-based
      detection format.

PMID- 23158335
TI  - Hot electron-induced cathodic electrochemiluminescence at oil film-covered carbon
      paste electrode and application to nano-molar determination of catechol.
AB  - Hot electron-induced cathodic electrochemiluminescence of the
      Ru(bpy)(3)(2+)/S(2)O(8)(2-) system was investigated at an oil film-covered carbon
      paste electrode (CPE) under cathodic pulse polarization for the first time.
      Compared with other electrodes, the CPE is of lower background, better stability
      and reproducibility. The method is also applied to the determination of catechol.
      Under the optimum conditions, the linear correlation between the quenched ECL
      intensity (DeltaI) and the logarithm of catechol concentration (logC(catechol))
      was observed over the range of 2.0*10(-10) mol/L-4.0*10(-9) mol/L and 4.0*10(-9)
      mol/L-4.0*10(-7) mol/L with the limit of detection (LOD) of 2.0*10(-10) mol/L,
      which is lower than the other reported methods. The proposed method is applied to
      determine catechol in reservoir water. The mean recoveries of 83.3%-99.0% and the
      relative standard deviations (RSDs) of 0.8%-2.2% were obtained.

PMID- 23158336
TI  - CuInS2 quantum dots-based fluorescence turn off/on probe for detection of
      melamine.
AB  - In this paper, a sensitive and simple method for the determination of melamine
      (MA) was developed based on the fluorescence changes of the water-soluble
      CuInS(2) quantum dots (QDs). The water-soluble CuInS(2) QDs capped by
      mercaptopropionic acid (MPA) was directly synthesized by hydrothermal method
      based on our previous report. The fluorescence emission of CuInS(2) QDs was
      quenched by the oxidation of the surface of the QDs with H(2)O(2), and the
      quenched fluorescence of CuInS(2) QDs could be recovered upon the addition of
      small amounts of MA, which might be due to the surface passivation of the
      CuInS(2) QDs by MA. The other amino acids such as glycine and lysine had no
      effect on the quenched fluorescence of CuInS(2) QDs. Under optimum conditions,
      there was a good linear relationship between the fluorescence intensity of
      CuInS(2) QDs and the concentration range of MA from 1.0*10(-8) to 1.0*10(-5)
      mol/L with a detection limit as low as 5 nM. The proposed method was successfully
      applied to detect trace MA in raw milk with satisfactory results. Compared with
      previous reports, the proposed method manifested several advantages such as high
      sensitivity, short analysis time, low cost and ease of operation.

PMID- 23158337
TI  - A novel molecularly imprinted impedimetric sensor for melamine determination.
AB  - A novel molecularly imprinted (MIP) impedimetric sensor was promoted for
      selective detecting melamine (MEL). The Au electrode modified with MIP poly (2
      mercaptobenzimidazole) (PMBI) was prepared by electrochemical polymerization of 2
      mercaptobenzimidazole (2-MBI) with cyclic voltammetry (CV) in the presence of
      template molecule MEL. The surface morphology and structure of MIP PMBI are
      characterized by atomic force microscopy (AFM), infrared spectra (IR),
      electrochemical impedance spectroscopy (EIS), and CV. The main driving force of
      recognition is the pi-donor-acceptor interaction between MEL and PMBI. The
      imprinted electrode could avoid the interference successfully. In addition, a
      linear response curve was obtained from 1.0*10(-8) M to 5.0*10(-5) M, with the
      detection limit of 3.0*10(-9) M. The sensor exhibits remarkable advantages, such
      as higher sensitivity, wider linear range and lower detection limit. The
      effective method has a potential application to monitor nonelectrochemically
      active substances in food analysis in the future.

PMID- 23158338
TI  - Highly sensitive and selective colorimetric detection of cartap residue in
      agricultural products.
AB  - The residue of pesticide has posed a serious threat to human health. Fast, broad
      spectrum detection methods are necessary for on-site screening of various types
      of pesticides. With citrate-coated Au nanoparticles (Au NPs) as colorimetric
      probes, a visual and spectrophotometric method for rapid assay of cartap, which
      is one of the most important pesticides in agriculture, is reported for the first
      time. Based on the color change of Au colloid solution from wine-red to blue
      resulting from the aggregation of Au NPs, cartap could be detected in the
      concentration range of 0.05-0.6 mg/kg with a low detection limit of 0.04 mg/kg,
      which is much lower than the strictest cartap safety requirement of 0.1 mg/kg.
      Due to the limited research on the rapid detection of cartap based on Au NPs, the
      performance of the present method was evaluated through aggregation kinetics,
      interference influence, and sample pretreatment. To further demonstrate the
      selectivity and applicability of the method, cartap detection is realized in
      cabbage and tea with excellent analyte concentration recovery. These results
      demonstrate that the present method provides an easy and effective way to analyze
      pesticide residue in common products, which is of benefit for the rapid risk
      evaluation and on-site screening of pesticide residue.

PMID- 23158339
TI  - Facile and tunable fabrication of Fe3O4/graphene oxide nanocomposites and their
      application in the magnetic solid-phase extraction of polycyclic aromatic
      hydrocarbons from environmental water samples.
AB  - An electrostatic self-assembly approach was employed to prepare
      Fe(3)O(4)/graphene oxide nanocomposites, and their application in the magnetic
      solid-phase extraction of polycyclic aromatic hydrocarbons from environmental
      samples was investigated. With the highly hydrophilic graphene oxide sheets and
      positively charged surface of the Fe(3)O(4) nanoparticles, the nanocomposites
      were synthesized through electrostatic interaction in aqueous solution.
      Simultaneously, the different loading amounts of Fe(3)O(4) onto the graphene
      oxide were easily controlled by changing the proportion of the initial
      precursors. The identity of the hybrid materials was confirmed using transmission
      electron microscopy, X-ray diffraction, X-ray photoelectron spectroscopy and a
      vibrating sample magnetometer. Five polycyclic aromatic hydrocarbons were
      selected as model analytes to validate the extraction performance of the
      Fe(3)O(4)/GO nanocomposite as a MSPE sorbent. The excellent adsorption property
      was attributed to the dominant roles of pi-pi stacking interaction and
      hydrophobic interaction. After optimizing the conditions, the results indicated
      that the recoveries of these compounds were in the range of 76.8-103.2%, with
      relative standard deviations ranging between 1.7% and 11.7%; the limits of
      detection were in the range of 0.09-0.19 ng mL(-1).

PMID- 23158340
TI  - Synthesis of highly dispersed mesostructured cellular foam silica sphere and its
      application in high-performance liquid chromatography.
AB  - Highly dispersed mesostructured cellular foam silica spheres of relatively
      uniform micrometer size (3.5-4.5 MUm) were successfully prepared using a triblock
      copolymer EO(20)PO(70)EO(20) as the structure-directing agent accompanied by TMB
      and K(2)SO(4). Both two additives have effective influence and K(2)SO(4) have
      better performance than other inorganic salts such as KCl and NaCl. The pore size
      and surface area were tuned by TMB and NH(4)F. The resultant S-MCFs were modified
      with C(18) group before being used as the HPLC stationary phase for effective
      separation of aromatic compounds and phthalic acid esters. The perfect spherical
      morphology and large pore volume gave rise to low and stable back pressure. High
      surface area, ultralarge pore size and unique pore structure would permit high
      flow rates and afford the possibility for fast separation.

PMID- 23158341
TI  - Detection of food-borne pathogens with DNA arrays on disk.
AB  - A DNA oligonucleotide array for duplex pathogen detection on a DVD platform is
      developed. The assay involves hybridization of PCR products and optical detection
      using compact disc technology. Different DNA array constructions for attachment
      of synthetic oligonucleotides on to DVD surface are evaluated, finding that
      streptavidin-biotin coupling method yielded the highest sensitivity in
      combination with enzymatic signal amplification. Issues of importance for the DNA
      array construction such immobilized probes design, PCR product labeling strategy
      and composition of the hybridization buffer were addressed. The methodology was
      proved scoring single nucleotide polymorphisms with high selectivity. The assay
      capability was also demonstrated by the identification of two pathogenic
      microorganisms in powder milk samples. In fifty minutes, the DVD-array system
      identifies Salmonella spp. and Cronobacter spp. (previously named Enterobacter
      sakazakii) precise and simultaneously with a sensitivity of 10(0) and 10(2)
      cfu/mL, respectively, in infant milk. Results were in good agreement with those
      obtained by quantitative real-time PCR.

PMID- 23158342
TI  - Blank and sample handling troubleshooting in ultratrace analysis of alkylphenols
      and bisphenol A by liquid chromatography tandem mass spectrometry.
AB  - Blank contamination is a notorious problem in the ultratrace analysis of
      alkylphenols and bisphenol A. The achievement of low detection limits is
      complicated due to the high background signals. Furthermore, overestimations and
      underestimations in the analytical results can occur when blank levels are not
      stable. Thus, a review of sources of blank contamination in this type of analysis
      was carried out. Several sources of contamination were identified and useful
      guidelines are proposed for the determination of these compounds in water samples
      by liquid chromatography coupled with mass spectrometry. The system contamination
      was maintained below 0.09 ng (reagent blank) for all compounds and below 0.003
      MUg L(-1) (procedure blank). The main improvement was obtained by using LC-MS
      grade solvent in the mobile phase and PTFE syringe filters for the filtration of
      the sample extracts. Sample handling aspects such as filtration and storage of
      the water samples were also considered. The filtration of the samples should be
      avoided because both contamination and adsorption problems were observed when
      different kinds of filters were assayed. The refrigerated storage of water
      samples should be limited to 5 days (without addition of methanol) or 8 days
      (with 5% methanol).

PMID- 23158343
TI  - Chemical boundary conditions for the classification of aerosol particles using
      computer controlled electron probe microanalysis.
AB  - A method for the classification of individual aerosol particles using computer
      controlled electron probe microanalysis is presented. It is based on chemical
      boundary conditions (CBC) and enables quick and easy processing of a large set of
      elemental concentration data (mass%), derived from the X-ray spectra of
      individual particles. The particles are first classified into five major classes
      (sea salt related, secondary inorganic, minerals, iron-rich and carbonaceous),
      after which advanced data mining can be performed by examining the elemental
      composition of particles within each class into more detail (e.g., by ternary
      diagrams). The CBC method is validated and evaluated by comparing its results
      with the output obtained with hierarchical cluster analysis (HCA) for well-known
      standard particles as well as real aerosol particles collected with a cascade
      impactor. The CBC method gives reliable results and has a major advantage
      compared to HCA. CBC is based on boundary conditions that are derived from
      chemical logical thinking and does not require a translation of a mathematical
      algorithm output as does HCA. Therefore, the CBC method is more objective and
      enables comparison between samples without intermediate steps.

PMID- 23158344
TI  - An evaluation of uncertainty associated to analytical measurements of selected
      polycyclic aromatic compounds in ambient air.
AB  - This paper presents an evaluation of uncertainty associated to analytical
      measurement of 18 polycyclic aromatic compounds (PACs) in ambient air by liquid
      chromatography with fluorescence detection (HPLC/FD). The study was focused on
      analyses of PM(10), PM(2.5) and gas phase fractions. Main analytical uncertainty
      was estimated for 11 polycyclic aromatic hydrocarbons (PAHs), four nitro
      polycyclic aromatic hydrocarbons (nitro-PAHs) and two hydroxy-polycyclic aromatic
      hydrocarbons (OH-PAHs) based on the analytical determination, reference material
      analysis and extraction step. Main contributions reached 15-30% and came from
      extraction process of real ambient samples, being those for nitro-PAHs the
      highest (20-30%). Range and mean concentration of selected PACs measured in gas
      phase and PM(10)/PM(2.5) particle fractions during a full year are also
      presented. Concentrations of OH-PAHs were about 2-4 orders of magnitude lower
      than their parent PAHs and comparable to those sparsely reported in literature.

PMID- 23158345
TI  - Miniaturized voltammetric stripping on screen printed gold electrodes for field
      determination of copper in atmospheric deposition.
AB  - The applicability of commercial screen-printed gold electrodes (SPGEs) connected
      to a portable potentiostat and a laptop has been explored to optimize a new
      square wave anodic stripping voltammetric method for on-site determination of
      soluble Cu(II) in atmospheric deposition samples taken around an industrial
      complex. Electrode conditioning procedures, chemical and instrumental variables
      have been optimized to develop a reliable method capable of measuring dissolved
      copper with a detection limit of 3.7 ng mL(-1), useful for pollution monitoring
      or screening purposes. The proposed method was tested with the SLRS-5 River Water
      for Trace Metals (recoveries 109.9-113.1%) and the SPS-SW2 Batch 121 Elements in
      Surface Waters (recoveries 93.2-97.6%). The method was applied to soluble Cu(II)
      measurement in liquid samples taken by a total atmospheric deposition collector
      modified with a quartz filter for soluble and insoluble elemental speciation. The
      voltammetric measurements on field samples were tested in the lab by a reference
      ICP-MS method, with good agreement. The proposed method proved capability for
      field operation during a two weeks monitoring campaign.

PMID- 23158346
TI  - Near real time detection of hazardous airborne substances.
AB  - A fast near real-time monitoring system for hazardous airborne substances, such
      as chemical warfare agents (CWA) is presented and limits of detection (LOD) for
      five CW simulants are determined. A tandem thermal desorber (TTD) continuously
      collects and pre-concentrates air. The pre-concentrated samples are then
      separated in a fast gas chromatographic (GC) run of 6.9min. and detected by a
      time-of-flight mass spectrometer (TOFMS). The GC-TOFMS signals are evaluated
      using chemometric methods for deconvolution and target identification. The high
      toxicity of nerve agents requires extremely low detection limits; for some as low
      as 100 ng/m(3) (10 ppt). The combination of TTD, TOFMS and chemometric data
      evaluation methods enables the system to fulfill this requirement. Calibration
      measurements for five different CWA simulants show lower limits of detection in
      the range of 10 ng/m(3)-60 ng/m(3) (1-11 ppt). In addition, the ability to detect
      trace concentrations of real CWA is demonstrated with a measurement of 30 pg
      Sarin on column. Several other real CWA measurements are shown, like sulfur
      mustard in diesel, lewisite under humid conditions and VX. As part of this work
      the influence of stationary film thickness on peak tailing of organophosphates is
      investigated for peak shape optimization.

PMID- 23158347
TI  - Analysis of the diastereoisomers of alliin by HPLC.
AB  - Garlic has been known for its therapeutic effects for centuries and is used
      worldwide as a functional food. The concentration of the active molecules could
      be enhanced by a better knowledge of their biosynthesis. The precursor of these
      compounds, alliin (a sulfur amino-acid) has been obtained by chemical synthesis.
      However, this synthesis route also leads to a diastereoisomer as co-product. This
      work describes the development of an analytical method which allows the
      separation and quantification of the two diastereoisomers in order to determine
      in which proportion the natural form can be produced. The HPLC method which was
      optimized and validated by accuracy profile exploits an original stationary phase
      consisting of porous graphitic carbon (PGC). Furthermore, the developped method
      was used to separate the diastereoisomers of methiin, another cysteine sulfoxide,
      and to analyze an aqueous extract of garlic. The ability to quantify the amount
      of natural alliin is valuable for further work on garlic molecules and their
      application for health protection.

PMID- 23158348
TI  - Rapid desorption electrospray ionization-high resolution mass spectrometry method
      for the analysis of melamine migration from melamine tableware.
AB  - Migration of melamine into foods from melamine tableware has been object of
      recent Rapid Alert System for Food and Feed (RASFF) notifications. In this
      context, a rapid and sensitive desorption electrospray ionization-high resolution
      mass spectrometry (DESI-HRMS) method was developed and validated for the
      determination of melamine migration from plastic materials. The migration test
      was performed using acetic acid 3% (w/v) as food simulant. Evaluation of DESI
      parameters in terms of choice of support, motion profile, geometrical
      configuration and operating conditions coupled to the use of an orbitrap mass
      analyzer allowed to achieve significant improvements in terms of selectivity and
      accuracy obtaining detection and quantitation limits at low microgram per
      kilogram level. A LC-ESI-MS method was also developed for confirmatory purposes.
      Both methods were applied to 44 melamine tableware samples available on Italian
      market in order to assess their compliance with the law. Different concentration
      levels ranging from 0.00773+/-0.0006 to 3.0+/-0.1 mg/kg were found after the
      third exposure to the simulant in new and used tableware with two samples out of
      44 being characterized by a melamine release higher than the legal limit, i.e.
      2.5 mg/kg. A two tailed t-test allowed to assess the good agreement between the
      quantitative results obtained applying the DESI-MS method with those provided by
      LC-ESI-MS, thus proving reliability of DESI-HRMS as rapid technique for the study
      of melamine release from plastic materials.

PMID- 23158349
TI  - Sensitive determination of sertraline by capillary electrophoresis with
      dispersive liquid-liquid microextraction and field-amplified sample stacking.
AB  - A novel method for the determination of sertraline using dispersive liquid-liquid
      microextraction (DLLME) coupled with capillary electrophoresis (CE) was
      developed. Acetone and dichloromethane were used as the disperser solvent and
      extraction solvent, respectively. A mixture of the extraction and disperser
      solvents was rapidly injected into a 1.0 mL aqueous sample to form a cloudy
      solution. After the extraction, sertraline was analyzed using CE that was
      equipped with UV detection. A 74-fold improvement in the sensitivity was observed
      when DLLME was used to extract sertraline. Since the DLLME extract residue was
      redissolved with 5 MUL of water that contained 20% methanol, the detection
      sensitivity was further enhanced through the use of field-amplified sample
      stacking (FASS). A 11-fold improvement in the sensitivity was obtained when FASS
      was used to on-line concentrate sertraline. Under optimal extraction and stacking
      conditions, the calibration curve, which ranged from 0.01 to 1 MUM was observed
      to be linear. The limit of detection (LOD) at a signal-to-noise ratio of 3 was
      2.5 nM for sertraline. An approximately 814-fold improvement in the sensitivity
      was observed for sertraline compare with injection of standard solution without
      the DLLME and FASS procedures. This developed method was successfully applied to
      the determination of sertraline in human urine samples.

PMID- 23158350
TI  - A simple HPLC-ESI-MS method for the direct determination of ten pteridinic
      biomarkers in human urine.
AB  - Pteridines are important biomarkers metabolites related to several biochemical
      pathways such as activation of the cell-mediated immune system, biosynthesis of
      neurotransmitters, etc. The level of pteridinic compounds in urine is considered
      as an important clinic criterion. In this work, a new liquid chromatography-mass
      spectrometry (LC-MS) method is proposed to determine several pteridinic
      biomarkers in urine samples using 6-methylpterin as internal standard (I.S.).
      Matrix effect was evaluated and several dilutions of urine were tested in order
      to study the evolution of signal suppression. Sample preparation was limited to
      10-fold dilution of the filtered urine followed by injection onto a reversed
      phase column. The signal was recorded in selected ion monitoring mode. The lowest
      limit of detection was found for pterin (values ranged from 1.70 to 3.88 ng mL(
      1)) whereas the highest limit was for xanthopterin (values ranged from 10.5 to
      49.9 ng mL(-1)) for healthy volunteers between 17 and 51 years old.

PMID- 23158351
TI  - Determination of phthalates and organophosphate esters in particulated material
      from harbour air samples by pressurised liquid extraction and gas chromatography
      mass spectrometry.
AB  - A method based on gas chromatography-mass spectrometry (GC-MS) combined with a
      pressurised liquid extraction (PLE) to determine four organophosphates, seven
      phthalate esters and bis(2-ethylhexyl) adipate in particulated material of
      harbour air samples has been developed. Some studies show that these compounds
      may cause hormone disrupting effects on human health. Moreover, the U.S.
      Environmental Protection Agency (EPA) has classified benzyl butyl phthalate and
      di(2-ethylhexyl) phthalate as possible human carcinogens.The chromatographic time
      per run analysis is less than 15 min and the complete separation of all compounds
      is achieved. The PLE was optimised with recoveries above 90% and the
      repeatability of the method with real samples is less than 11% (%RSD, n=4). The
      MDLs (0.004-0.4 ng m(-3)) and MQLs (0.02-2 ng m(-3)) are limited by the fact of
      some compounds are present in low levels in sampling blank filters.The method was
      successfully applied in several samples and most of the compounds under study
      were found. The most relevant values were the high concentration of di-iso-butyl
      phthalate (between 28 and 529 ng m(-3)) and the significant concentration of di(2
      ethylhexyl) phthalate (between MQL and 22 ng m(-3)). In addition, benzyl butyl
      phthalate was also detected in some samples but at low concentration levels
      (between MQL to 0.2 ng m(-3)).

PMID- 23158352
TI  - Simple quantification of phenolic compounds present in the minor fraction of
      virgin olive oil by LC-DAD-FLD.
AB  - This paper presents the results of the study on the extraction, identification
      and quantification of a group of important phenolic compounds in virgin olive oil
      (VOO) samples, obtained from olives of various varieties, by liquid
      chromatography coupled to UV-vis and fluorescence detection. Sixteen phenolic
      compounds belonging to different families have been identified and quantified
      spending a total time of 25 min. The linearity was examined by establishing the
      external standard calibration curves. Four order linear ranges and limits of
      detection ranging from 0.02 to 0.6 MUg mL(-1) and 0.006 to 0.3 MUg mL(-1) were
      achieved using UV-vis and fluorescence detection, respectively. Regarding the
      real samples, for the determination of the phenolic compounds in higher
      concentrations (hydroxytyrosol and tyrosol) a simple liquid-liquid extraction
      with ethanol was used to make the sample compatible with the mobile phase.
      Recovery values close to 100% were obtained. However, a previous solid phase
      extraction with Diol cartridges was necessary to concentrate and separate the
      minor phenolic compounds of the main interferences. The parameters affecting this
      step were carefully optimized and, after that, recoveries near 80-100% were
      obtained for the rest of the studied phenolic compounds. Also, the limits of
      detection were improved 15 times. Finally, the standard addition method was
      carried out for each of the analytes and no matrix effect was found, so the
      quantification of the 16 phenolic compounds from different monovarietal VOO was
      carried out by using the corresponding external standard calibration plot.

PMID- 23158353
TI  - Enhanced Raman spectroscopic discrimination of the geographical origins of rice
      samples via transmission spectral collection through packed grains.
AB  - Transmission Raman spectroscopy has been effectively utilized for the
      discrimination of rice samples according to geographical origin. Since the
      constituents of rice are heterogeneously distributed and/or localized in a grain,
      the collection of Raman spectra providing a better compositional representation
      of packed rice grains is an essential requirement for accurate analysis. The
      optimal packing thickness yielding the most reproducible transmission spectra was
      initially determined. Internal propagation of radiation was more sensitively
      influenced by random packing when a packing was thinner; while, a thicker packing
      largely attenuated transmitting Raman signal and eventually degraded the signal
      to-noise ratio of collected spectra. At the determined packing thickness,
      transmission spectra of all rice samples were collected, and discrimination into
      two different geographical origins was performed using principal component
      analysis (PCA) combined with linear discriminant analysis (LDA). For comparison,
      back-scattering Raman spectra of the same samples were also collected. The
      discrimination accuracy was improved when Raman spectra collected directly
      through the packed rice grains were used. Since the constituents of rice were not
      homogeneously distributed in a grain as confirmed using Raman microscopy, the
      transmission measurement enabling transversal sampling across a packing of rice
      grains was better for compositional representation of individual grains in the
      packing and able to recognize minute spectral differences between two groups,
      ultimately leading to more accurate discrimination of geographical origin.

PMID- 23158354
TI  - Development and validation of a simple and sensitive high performance liquid
      chromatographic method for the simultaneous determination of anastrozole,
      bicalutamide, tamoxifen, and their synthetic impurities.
AB  - A simple and sensitive analytical method for simultaneous determination of
      anastrozole, bicalutamide, and tamoxifen as well as their synthetic impurities,
      anastrozole pentamethyl, bicalutamide 3-fluoro-isomer, and tamoxifen e-isomer,
      was developed and validated by using high performance liquid chromatography
      (HPLC). The separation was achieved on a Symmetry((r)) C-8 column (100*4.6 mm
      i.d., 3.5 MUm) at room temperature (+/-24  degrees C), with a mobile phase
      consisting of acetonitrile/water containing 0.18% N,N dimethyloctylamine and pH
      adjusted to 3.0 with orthophosphoric acid (46.5/53.5, v/v) at a flow rate of 1.0
      mL min(-1) within 20 min. The detection was made at a wavelength of 270 nm by
      using ultraviolet (UV) detector. No interference peaks from excipients and
      relative retention time indicated the specificity of the method. The calibration
      curve showed correlation coefficients (r) >0.99 calculated by linear regression
      and analysis of variance (ANOVA). The limit of detection (LOD) and limit of
      quantitation (LOQ), respectively, were 2.2 and 6.7 MUg mL(-1) for anastrozole,
      2.61 and 8.72 MUg mL(-1) for bicalutamide, 2.0 and 6.7 MUg mL(-1) for tamoxifen,
      0.06 and 0.22 MUg mL(-1) for anastrozole pentamethyl, 0.02 and 0.07 MUg mL(-1)
      for bicalutamide 3-fluoro-isomer, and 0.002 and 0.007 MUg mL(-1) for tamoxifen e
      isomer. Intraday and interday relative standard deviations (RSDs) were <2.0%
      (drugs) and <10% (degradation products) as well as the comparison between two
      different analysts, which were calculated by f test.

PMID- 23158355
TI  - Optimization of matrix solid phase dispersion coupled with gas chromatography
      electron capture detection for determination of chlorinated pesticides in soil.
AB  - A fast, simple and efficient technique based on matrix solid phase dispersion has
      been presented for extraction and clean-up of some chlorinated pesticides and
      derivative products; alpha-BHC, beta-BHC, gamma-BHC, delta-BHC, heptachlor,
      aldrin, dieldrin, endrin, endosulfan 1, endosulfan 2, 4,4'-DDT, 4,4'-DDE, 4,4'
      DDD, heptachlor epoxide, endrin aldehyde, endosulfan sulfate. Box-Behnken
      response surface methodology was employed for optimization of the extraction
      efficiency. As the optimized procedure, 0.5 g of dried and sieved soil samples
      were mixed with 2.0 g of 10% C18 in silica (w/w) as dispersant and after
      transferring into the extraction tube they were extracted with 8 mL of
      dichloromethane-n-hexane (1:1, v/v). Gas chromatography with electron capture
      detector was used for selective and sensitive determination of the analytes.
      Recoveries for the extraction of the proposed analytes were calculated and were
      satisfying (more than 75%), except for endrin aldehyde (59%) and endosulfan
      sulfate (62%). Also the method was linear over the calibration range (R(2)>0.991)
      and the quantitative results were reasonably reproducible and sensitive (LODs
      ranged between 0.3 and 1.8 ng g(-1)).

PMID- 23158356
TI  - Simultaneous determination of alpha-, beta- and gamma-asarone in Acorus
      tatarinowii by microemulsion electrokinetic chromatography with [BMIM]PF6 as oil
      phase.
AB  - In the present study, a rapid and repeatable microemulsion electrokinetic
      chromatography (MEEKC) method was developed for the simultaneous determination of
      three isomers (alpha-, beta- and gamma-asarone) in Acorus tatarinowii by using
      ionic liquid 1-butyl-3-methylimidazolium hexafluorophosphate ([BMIM]PF(6)) as oil
      phase. Experimental parameters including the microemulsion compositions
      (concentrations of surfactant, co-surfactant and oil phase), pH, concentration of
      borate buffer, capillary temperature and voltage were intensively investigated.
      Finally, the main compounds in the methanol extract of A. tatarinowii were well
      separated within 11 min using a running buffer composed of 40 mmol/L sodium
      dodecyl sulfonate (SDS), 2.0 mol/L n-propanol, 8 mmol/L [BMIM]PF(6) in 10 mmol/L
      borate buffer of pH 9.5. The developed method was applied to determine the
      contents of alpha-, beta- and gamma-asarone in A. tatarinowii from five different
      producing areas in China (Anhui, Hebei, Sichuan, Zhejiang and Chongqing). The
      results indicated that the contents of three asarones are quite different in the
      investigated A. tatarinowii samples. On the other hand, the MEEKC with ionic
      liquid as oil phase should be a promising method for the analysis of volatile
      components especially isomers in medicinal herbs.

PMID- 23158357
TI  - Phase transfer hollow fiber liquid phase microextraction combined with
      electrothermal vaporization inductively coupled plasma mass spectrometry for the
      determination of trace heavy metals in environmental and biological samples.
AB  - A new method of phase transfer hollow fiber liquid phase microextraction (PT-HF
      LPME) combined with electrothermal vaporization inductively coupled plasma mass
      spectrometry (ETV-ICP-MS) has been developed for the determination of trace Co,
      Pd, Cd and Bi in environmental and biological samples. In PT-HF-LPME, an
      intermediate solvent (1-butanol) was added into the sample solution to ensure the
      maximum contact area between the target metal ions and the chelating reagent (8
      hydroxyquinoline, 8-HQ), which accelerated the formation of 8-HQ-metal complexes
      and their subsequent extraction by extraction solvent (toluene). The experimental
      parameters affecting the extraction efficiency of PT-HF-LPME for the target
      metals were studied by simplex optimization and orthogonal array design (OAD)
      experiments. Under the optimized conditions, the enrichment factors for Co, Pd,
      Cd and Bi were 110, 393, 121 and 111-fold, respectively, the limits of detection
      (LODs, 3sigma) ranged from 3.7 to 8.3 ng L(-1). The relative standard deviations
      (RSDs, c=0.5 ng mL(-1), n=7) were 8.7, 6.2, 12.4 and 12.9% for Co, Pd, Cd and Bi,
      respectively. To validate the accuracy of the proposed method, two Certified
      Reference Materials of GSBZ50009-88 Environment Water and GBW09103 Human Urine
      were analyzed, and the results obtained for Cd were in good agreement with the
      certified values. Finally, the developed method was successfully applied to the
      analysis of Co, Pd, Cd and Bi in lake water and human urine samples.

PMID- 23158358
TI  - Analysis of arsenic species in fish after derivatization by GC-MS.
AB  - The derivatization of organoarsenic compounds by different reagents like
      thioglycolates or dithiols and the subsequent analysis by GC-MS as a molecular
      specific technique was investigated and described. The possible derivatization
      reagents methyl- and ethylthioglycolate (TGM and TGE), 1,3-propane- and 1,5
      pentanedithiol (PDT and PeDT), which transfer the polar and nonvolatile analytes
      dimethylarsenate (DMA), monomethylarsonate (MMA), arsenite and arsenate into
      volatile compounds, were evaluated. The application for real samples like fish
      material was also studied. In addition the gas chromatographic separation and
      resolution was optimized and experiments were carried out to determine the
      highest derivatization rates. Derivatization reagents were evaluated in terms of
      quantity and stability of the formed chemical species. All derivatization
      products were characterized by mass spectrometry in order to identify the
      separated arsenic species. The most efficient conversion of DMA and MMA was
      observed by using ethylthioglycolate as derivatization agent. Finally, the
      derivatization procedure and the GC-MS-method were validated to determine
      linearity, precision, selectivity, analytical limiting values and recoveries. For
      the proposed method a limit of detection (LOD) of 5.8 pg for DMA and 14.0 pg for
      MMA was found. The accuracy was established by comparing the mean value measured
      for DMA in the certified reference material BCR-627 (tuna fish) with the
      certified one. MMA was not quantified in marine samples due to its low content.
      In shrimp samples DMA was not detectable. For codfish a DMA-content of 0.20+/
      0.004 mg kg(-1), for "Surstromming" an amount of 0.38+/-0.02 mg kg(-1) and for
      herring, which showed the highest amount of DMA, a content of 1.15+/-0.03 mg kg(
      1) was determined.

PMID- 23158359
TI  - Development and validation of a stability indicative HPLC-PDA method for
      kaurenoic acid in spray dried extracts of Sphagneticola trilobata (L.) Pruski,
      Asteraceae.
AB  - A gradient stability indicative HPLC-UV method was developed and validated for
      assay of the marker kaurenoic acid (KA) in spray dried extract of Sphagneticola
      trilobata (L.) Pruski. The marker, and another unidentified polar component, were
      separated on a Luna Phenomenex C(18) column (250*4.6 mm, 5 MUm) with mobile phase
      composed of acetonitrile:acidified water pH 3.0 with phosphoric acid, in a
      gradient run of 40 min; at a flow rate of 1.0 mL min(-1), 35  degrees C, using
      wavelengths of 210 and 338 nm. The method was linear over a KA concentration
      range of 4.5-30.0 MUg mL(-1), without interference of the herbal matrix on the
      linearity of the method. The RSD% values for the intra- and inter-day precision
      studies were <2.0 and <8.0% for inter-laboratorial study. The method showed
      excellent KA recovery (99.0%). The LOQ value was found to be 1.13 MUg mL(-1) and
      the method proved to be robust for small, deliberate changes in temperature and
      pH of the mobile phase with RSD%<2.5% for the KA assay. A forced degradation
      study of S. trilobata dried extract was conducted under conditions of visible
      light (1.200.000 l*h(-1)) and UV (200 Whm(-2)) irradiation, acid (0.5 mol L(-1)
      HCl, 30 min), basic (1 mol L(-1) NaOH, 2 h) and oxidative (30% H(2)O(2), 4h)
      hydrolysis, in order to develop a gradient stability-indicating LC-UV method for
      KA quantification, the selected marker, and also to detect the major polar
      components of the extract, under investigation. The KA contents remaining after
      these stress conditions were 72.3, 70.0, 97.6, 65.8 and 87.0%, respectively. The
      alkaline conditions resulted in higher degradation for the unknown polar
      components of the extract, without interference of supplementary peaks at the
      retention time of the KA. This method can be used for the KA assay and
      qualitative analysis of polar components in stability study of spray dried
      extracts of S. trilobata, for subsequent use in the quality control of dosage
      forms.

PMID- 23158360
TI  - Determination of total leachable bisphenol A from polysulfone membranes based on
      multiple consecutive extractions.
AB  - The paper presents the development of a multiple consecutive extraction method
      enabling the determination of the total amount of bisphenol A (BPA) released from
      porous polysulfone (PS) membranes in a hemodialyzer or hemoconcentrator under
      simulated-use conditions. The levels of BPA were determined using solid phase
      extraction (SPE) coupled with high performance liquid chromatography-mass
      spectrometry (HPLC-MS). We demonstrated that it was difficult to determine the
      total amount of BPA released from the PS membranes using a single extraction
      method with finite solvent volume because of the chemical equilibrium between the
      extraction solution and the polymer phase. Repeated extractions gave more
      accurate results than a single extraction for the determination of the total
      amount of leachables in porous membranes. A general equation was derived to fit
      the elution profile of BPA released during multiple consecutive extractions.

PMID- 23158361
TI  - Ion chromatography combined with online electrochemical derivatization and
      fluorescence detection for the determination of carbamazepine in human plasma.
AB  - This paper describes the determination of carbamazepine (CBZ) in human plasma
      using ion chromatography combined with online electrochemical derivatization and
      fluorescence detection. Separation of CBZ with anion exchange column was
      demonstrated to be feasible using either basic (10 mM NaOH) or acidic (0.1 M
      H(3)PO(4)) reagent with a small amount of acetonitrile (ACN) added as eluent.
      Electrochemical derivatization of CBZ into a strongly fluorescent product, which
      could be carried out only under the acidic condition, was investigated via the
      previously reported electrolytic cell (EC), as well as two modes of
      acidification. The linear range of CBZ for human plasma was between 10-2000 MUg
      L(-1) under the optimized experimental conditions. The limit of detection (LOD,
      S/N=3) was 1.3 MUg L(-1) and the relative standard deviation (RSD, n=7) was 2.6%.
      Better sensitivity and selectivity of the present method were demonstrated in
      comparison with ion chromatography with ultraviolet detection (IC-UV). The spiked
      recoveries of CBZ in 2 human plasma samples were 78.5 and 114%, respectively.

PMID- 23158362
TI  - Improved potentiometric response of all-solid-state Pb(2+)-selective electrode.
AB  - Zero-current ion-flux has a great influence on the characteristics of the ion
      selective electrodes. In this work the improvement of analytical performance of
      all-solid-state Pb(2+)-selective membrane electrodes was demonstrated by
      adjusting the transmembrane ion flux. The study is focused on the relationship
      between the conditioning solution and the linear working range of the obtained
      electrodes for different sample matrixes. Results show that the electrode with
      appropriate conditioning keeps good reproducibility within linear working range.
      The utility of the electrode has been tested by successfully determining Pb(2+)
      concentration in real water samples.

PMID- 23158363
TI  - Increased population of central memory T cells in circulating peripheral blood of
      psoriasis patients.

PMID- 23158364
TI  - MiR-23a regulates DNA damage repair and apoptosis in UVB-irradiated HaCaT cells.
AB  - BACKGROUND: MiRNAs remain at a constant level under physiological conditions.
      However, how the expression of miRNAs is regulated and what are the roles of
      miRNAs in response to UVB damage to skin cells is still not fully understood. In
      our preliminary study, we observed that miR-23a was upregulated following a
      treatment with a DNA repair agent and UVB exposure. OBJECTIVE: To investigate the
      regulation and function of miR-23a in response to UVB-induced injury in human
      keratinocyte cell line (HaCaT) cells. METHODS: The changes in expression of miR
      23a after UVB irradiation of HaCaT cells were measured by qRT-PCR. The level of
      miR-23a expression was also modulated by transfecting with a miR-23a mimic or an
      inhibitor. Cell viability was assessed by the CCK-8 assay. Immunofluorescence
      staining and Southwestern dot blotting were used to detect the levels of
      cyclobutane pyrimidine dimers (CPDs). Flow cytometry, Hoechst staining, and
      measurements of caspase-3 activity were employed to measure the incidence of
      apoptosis. The mRNA and protein expression levels of genes related to DNA
      reparation and apoptosis, such as topoisomerase-1, caspase-7, and STK4, were
      analyzed by qRT-PCR and Western blotting, respectively. RESULTS: MiR-23a
      expression was remarkably up-regulated at 4 h and 24 h after the UVB irradiation
      of HaCaT cells. UVB-induced apoptosis was increased by down-regulation of miR
      23a. UVB-induced removal of CPDs was accelerated by miR-23a up-regulation and
      delayed by miR-23a down-regulation. Forced over-expression of miR-23a decreased
      the expression of UVB-induced topoisomerase-1?caspase7?STK4 at both the mRNA and
      protein levels, and these effects were reversed by down-regulation of miR-23a.
      CONCLUSION: The protection of HaCaT cells against UVB damage is afforded by miR
      23a through regulation of topoisomerase-1?caspase7?STK4, and this miRNA may be a
      novel therapeutic target in skin diseases related to UVB radiation.

PMID- 23158365
TI  - Histopathological characteristics and oxidative injury secondary to atrial
      fibrillation in the left atrial appendages of patients with different forms of
      mitral valve disease.
AB  - BACKGROUND: The prevalence of atrial fibrillation (AF) and the frequency
      cardioversion of AF postoperatively are different in different forms of mitral
      valve disease. We hypothesized that these differences would relate to different
      extent of histopathological characteristics and oxidative injury in different
      forms of mitral valve diseases. METHODS: Left atrial appendages were obtained
      from 24 patients of mitral valve disease with or without AF undergoing mitral
      valve surgery. Control data were obtained from left appendages of 4 persons in
      normal sinus rhythm (SR) died of traffic accident. Histopathology,
      immunohistochemistry, Western blotting and enzyme kinetics examination were
      performed to assess the extent of histopathological characteristics and oxidative
      injury. RESULTS: The average cross-sectional diameter of atrial myocyte of mitral
      stenosis (MS)+AF, MS+SR, mitral regurgitation (MR)+AF, MR+SR and control was
      25.62+/-7.56 MUm, 20.20+/-9.34 MUm, 21.69+/-7.00 MUm, 13.93+/-4.32 MUm and 9.81+/
      2.34 MUm, respectively. Significantly statistical difference was found between
      each group (P<.05). Increased degree of atrial interstitial fibrosis was seen
      both in MS and MR with AF patients compared to other groups (P<.05), and the
      extent of fibrosis was more remarkable in MR patients compared to MS patients
      (P<.05). The extent of 3-nitrotyrosine (3-NT) immunoreactivity significantly
      increased in the patients with MS and AF compared to those of MR and AF (P<.05),
      and the immunoprevalence of 3-NT was significantly increased in patients of MS
      and SR compared to those of MR and SR (P<.05). Correlation analysis demonstrated
      a negative correlation between creatine kinase (CK) activity and extent of 3-NT
      immunoreactivity in atrial tissues (r=-0.382, P<.05). Significant decreases in CK
      activity were observed in myocardium from all patients of mitral valve disease
      with or without AF compared to controls (P<.05). Western blotting demonstrating
      an increased prevalence of 3-NT formation in CK-MM was detected compared to
      control group (P<.05). Correlation analysis demonstrated a negative correlation
      between CK-MM activity and extent of CK-MM tyrosine nitration (r=-0.446, P<.05).
      CONCLUSIONS: In different forms of mitral valve disease with different cardiac
      rhythm, the extent of histopathological characteristics and oxidative injury are
      different. Histopathological characteristics and oxidative injury not only relate
      to mitral valve disease but also relate to the development and sustain of AF.

PMID- 23158366
TI  - What do young women think about having a chlamydia test? Views of women who
      tested positive compared with women who tested negative.
AB  - OBJECTIVE: To determine young women's experience of having a chlamydia (Chlamydia
      trachomatis) test as part of a chlamydia incidence study, and to determine how
      women who tested positive during the study experienced having a test compared
      with the experience of women who always tested negative. METHODS: Women in an
      Australian chlamydia incidence study were tested at 3- to 6-monthly intervals
      during a 12-month period. At the final stage of the study, the women completed a
      questionnaire about how they felt about testing positive or how they anticipated
      they might feel about testing positive if they only tested negative. Questions
      about future sexual behaviour and testing were included. RESULTS: The
      questionnaire was completed by 872 out of 1116 (78%) women, including 67 women
      who tested positive. Many women (75%) felt anxious when having a chlamydia test
      but women who tested positive were less concerned about their future health (61%
      v. 81%, P<0.01), were less concerned about their partner's reactions (62% v. 79%,
      P<0.01) and were more likely to discuss their diagnosis with other people (57% v.
      36%, P<0.01). CONCLUSIONS: The participants in the study were pleased to have
      been tested and supported a screening program. Women who tested positive were
      less concerned about having a positive result than women who tested negative
      anticipated they might be. IMPLICATIONS: Clinicians need to be aware that having
      a chlamydia test can cause anxiety in young women and for a screening program to
      be successful, this must be addressed.

PMID- 23158367
TI  - Biomechanics of the normal and arthritic ankle joint.
AB  - Understanding biomechanics of the normal and arthritic ankle joint can aid in
      analysis of an underlying clinical problem and provide a strategic basis for a
      more optimal management. The challenge to the clinician and the biomechanist is
      that the mechanical complexity of the ankle joint still clouds current
      understanding. This article provides an overview of current understanding of
      functional ankle anatomy, how this function can be altered in the degenerated
      ankle, and how surgical intervention further affects foot and ankle biomechanics.
      The focus is on how altered loading of neighboring joints in the midfoot and
      hindfoot may induce postoperative joint remodeling and can manifest in secondary
      clinical problems.

PMID- 23158368
TI  - Ankle arthrodesis versus total ankle replacement: how do I decide?
AB  - Taking into account numerous individual criteria, the correct indication
      substantially influences the outcome of patients with end-stage ankle arthritis
      treated by ankle arthrodesis or total ankle replacement. The purpose of this
      report is to assist the foot and ankle surgeon or orthopedic surgeon involved in
      choosing ankle arthrodesis or total ankle replacement in decision-making.
      Balancing the criteria that are discussed in consideration of the recent relevant
      literature and evidence available, the surgeon is directed to the correct
      individual decision.

PMID- 23158369
TI  - The concept of ankle joint preserving surgery: why does supramalleolar osteotomy
      work and how to decide when to do an osteotomy or joint replacement.
AB  - The structure of the ankle is stabilized by bone, and external force is
      distributed to the adjacent intertarsal joints, reducing the vulnerability of the
      joint to osteoarthritis. Joint-preserving surgical techniques include
      arthroscopic debridement, ligament reconstruction, distraction arthroplasty, and
      osteotomy. Supramalleolar osteotomy to treat varus-type osteoarthritis of the
      ankle is also known as "low tibial osteotomy," as opposed to "high tibial
      osteotomy" to treat varus-type osteoarthritis of the knee.

PMID- 23158370
TI  - Total ankle replacement for rheumatoid arthritis of the ankle.
AB  - Rheumatoid arthritis is an autoimmune disease that may affect multiple joints,
      both small and large, and leads to numerous complications. The standard surgical
      treatment for a rheumatoid arthritic ankle has been an arthrodesis. The ideal
      candidate for an ankle replacement in a rheumatoid patient is one who is
      moderately active, has a well-aligned ankle and heel, and a fair range of motion
      in the ankle joint. Good surgical technique and correction of any hindfoot
      deformity will result in satisfactory alignment of the ankle with regard to the
      mechanical axis, and this will lead to increased prosthetic longevity.

PMID- 23158371
TI  - Mobile- and fixed-bearing total ankle prostheses: is there really a difference?
AB  - Approximately 1% of the world's adult population is affected by ankle
      osteoarthritis (OA). Therapeutic options include conservative and surgical
      measures. Because of substantial progress in total ankle replacement, ankle
      fusion is no longer the "gold standard" therapy for end-stage ankle OA. Various
      ankle prostheses have been designed and are currently available. This article
      reviews the in vitro studies addressing the biomechanics and kinematics of the
      replaced ankle. Furthermore, a systematic literature review was conducted to
      assess possible differences in clinical outcomes, including prosthesis
      survivorship and postoperative range of motion between mobile- and fixed-bearing
      total ankle prostheses.

PMID- 23158372
TI  - Techniques and pitfalls with the Salto prosthesis: our experience of the first 15
      years.
AB  - The Salto total ankle replacement system has shown to be a viable alternative in
      the treatment of symptomatic arthritis. However, although outcomes after total
      ankle replacement are promising, an exact analysis of surgical technique could
      help to improve them. Based on a 15 years experience with the Salto Total Ankle
      replacement system, the uthors discuss the surgical technique and its pitfalls,
      its inications and limitations in current practice.

PMID- 23158373
TI  - Total ankle replacement using HINTEGRA, an unconstrained, three-component system:
      surgical technique and pitfalls.
AB  - Total ankle replacement (TAR) has become a valuable treatment option in patients
      with end-stage ankle osteoarthritis. One popular 3-component system, the HINTEGRA
      TAR, is an unconstrained system that provides inversion-eversion stability. More
      natural biomechanics of the replaced ankle may be expected when anatomic
      considerations drive prosthesis design. The HINTEGRA prosthesis includes 2
      anatomically contoured metal components and a polyethylene insert, providing
      axial rotation and physiologic flexion-extension mobility. This article describes
      the HINTEGRA TAR design and surgical technique. Use of the prosthesis for complex
      hindfoot reconstruction in patients with an osteoarthritic, varus, or valgus
      ankle deformity is described.

PMID- 23158374
TI  - The mobility total ankle replacement: techniques and pitfalls.
AB  - The Mobility total ankle replacement (DePuy, Leeds, United Kingdom) is an
      uncemented, 3-component, mobile-bearing design. This article highlights the
      design rationale and explains the surgical technique with the Mobility implant,
      as well as offering technical tips and pitfalls gained through personal
      experiences and literature review. The tibial component has a flat articular
      surface and a conical intramedullary stem on the tibial side.

PMID- 23158375
TI  - Treatment of the arthritic valgus ankle.
AB  - The ankle joint is part of a biomechanical hindfoot complex. Approximately 1% of
      the world's adult population is affected by ankle osteoarthritis (AO). Trauma is
      the primary cause of ankle OA, often resulting in varus or valgus deformities.
      Only 50% of patients with end-stage ankle OA have a normal hindfoot alignment.
      The biomechanics and morphology of the arthritic valgus ankle is reviewed in this
      article and therapeutic strategies, including joint preserving and nonpreserving
      modalities are presented. Pitfalls are discussed and the literature is reviewed
      regarding outcomes in patients with valgus deformity who underwent total ankle
      replacement.

PMID- 23158376
TI  - Surgical treatment of the arthritic varus ankle.
AB  - Within the past several years, the arthritic varus ankle has been addressed
      extensively in Foot and Ankle Clinics, with numerous excellent reviews by
      particularly knowledgeable authors. To support these outstanding contributions,
      this article provides a practical approach to this challenging constellation of
      foot and ankle abnormalities. Varus ankle arthritis exists on a continuum that
      prompts the treating surgeon to be familiar with a spectrum of surgical
      solutions, including joint-sparing realignment, arthroplasty, and arthrodesis.
      Each of these treatment options is addressed with several expanded case examples
      and supports the management approaches with the available pertinent literature.

PMID- 23158377
TI  - Revision total ankle replacement.
AB  - This review of the current literature regarding total ankle replacement (TAR)
      revision surgery focuses on the causes for implant failure, how to deal with the
      clinical dilemmas of pain and stiffness following TAR, the management of
      asymptomatic peri-implant cyst formation, and the management of the distal tibia
      and talus during revision surgery.

PMID- 23158378
TI  - Management of specific complications related to total ankle arthroplasty.
AB  - Total ankle arthroplasty (TAA) has evolved over time and modern 3-component
      implants offer good and reliable clinical results. Despite recent improvements,
      TAA is still associated with a relatively high incidence of complications.
      Surgeon experience seems to play the most important role. This review highlights
      the most common intraoperative and postoperative complications, such as malleolar
      fracture, impingement, cyst formation, malalignment, and loosening, and offers a
      differentiated concept for their management.

PMID- 23158379
TI  - The New Zealand Joint Registry: report of 11-year data for ankle arthroplasty.
AB  - This article describes the results of the first 11 years of ankle arthroplasty
      data for the New Zealand Joint Registry. The main purpose is to collect accurate
      outcome information regarding these procedures and to guide orthopedic surgeons
      in the care of their patients. Trends can often be identified early, and implants
      with higher revision rates can be identified. In addition, individual surgeons
      can be given data that compare their performance with the collective data,
      providing invaluable feedback. Patient-based questionnaires are highly important
      for gauging the results of surgery. Patient response rates have been less than
      optimal, particularly after revision surgery.

PMID- 23158380
TI  - Total ankle replacement. Preface.

PMID- 23158381
TI  - Enhanced electrical properties of vertically aligned carbon nanotube-epoxy
      nanocomposites with high packing density.
AB  - During their synthesis, multi-walled carbon nanotubes can be aligned and
      impregnated in a polymer matrix to form an electrically conductive and flexible
      nanocomposite with high backing density. The material exhibits the highest
      reported electrical conductivity of CNT-epoxy composites (350 S/m). Here, we show
      how conductive atomic force microscopy can be used to study the electrical
      transport mechanism in order to explain the enhanced electrical properties of the
      composite. The high spatial resolution and versatility of the technique allows us
      to further decouple the two main contributions to the electrical transport: (1)
      the intrinsic resistance of the tube and (2) the tunneling resistance due to
      nanoscale gaps occurring between the epoxy-coated tubes along the composite. The
      results show that the material behaves as a conductive polymer, and the
      electrical transport is governed by electron tunneling at interconnecting CNT
      polymer junctions. We also point out the theoretical formulation of the nanoscale
      electrical transport between the AFM tip and the sample in order to derive both
      the composite conductivity and the CNT intrinsic properties. The enhanced
      electrical properties of the composite are attributed to high degree of
      alignment, the CNT purity, and the large tube diameter which lead to low junction
      resistance. By controlling the tube diameter and using other polymers, the
      nanocomposite electrical conductivity can be improved.

PMID- 23158382
TI  - A prevalence-based approach to societal costs occurring in consequence of child
      abuse and neglect.
AB  - BACKGROUND: Traumatization in childhood can result in lifelong health impairment
      and may have a negative impact on other areas of life such as education, social
      contacts and employment as well. Despite the frequent occurrence of
      traumatization, which is reflected in a 14.5 percent prevalence rate of severe
      child abuse and neglect, the economic burden of the consequences is hardly known.
      The objective of this prevalence-based cost-of-illness study is to show how
      impairment of the individual is reflected in economic trauma follow-up costs
      borne by society as a whole in Germany and to compare the results with other
      countries' costs. METHODS: From a societal perspective trauma follow-up costs
      were estimated using a bottom-up approach. The literature-based prevalence rate
      includes emotional, physical and sexual abuse as well as physical and emotional
      neglect in Germany. Costs are derived from individual case scenarios of child
      endangerment presented in a German cost-benefit-analysis. A comparison with
      trauma follow-up costs in Australia, Canada and the USA is based on purchasing
      power parity. RESULTS: The annual trauma follow-up costs total to a margin of EUR
      11.1 billion for the lower bound and to EUR 29.8 billion for the upper bound.
      This equals EUR 134.84 and EUR 363.58, respectively, per capita for the German
      population. These results conform to the ones obtained from cost studies
      conducted in Australia (lower bound) and Canada (upper bound), whereas the result
      for the United States is much lower. CONCLUSION: Child abuse and neglect result
      in trauma follow-up costs of economically relevant magnitude for the German
      society. Although the result is well in line with other countries' costs, the
      general lack of data should be fought in order to enable more detailed future
      studies. Creating a reliable cost data basis in the first place can pave the way
      for long-term cost savings.

PMID- 23158383
TI  - Pacemaker malfunction due to mechanical failure of the lead-header interface.
AB  - An 8 year old female spayed Boxer dog, diagnosed with concurrent vasovagal
      syncope and arrhythmogenic right ventricular cardiomyopathy, presented for
      routine evaluation approximately three months following epicardial pacemaker
      implantation. Routine device interrogation revealed intermittent loss of
      ventricular capture and intermittent failure to appropriately sense. Following
      evaluation of chronic impedance data, failure of the pacemaker lead-header
      interface or lead conductor fracture was suspected. Radiographic and pacemaker
      interrogator findings suggested incomplete lead insertion into the device header
      with intermittent loss of ventricular capture and variable pacemaker sensing. We
      hypothesize that either the presence of a loose or cross-threaded set screw or
      operator error at the time of device implantation may have caused this
      complication. This report details the diagnosis of mechanical failure of the lead
      header interface, a complication not previously reported in a veterinary patient.

PMID- 23158384
TI  - The contested status of cosmetic and reconstructive plastic surgery.

PMID- 23158385
TI  - The "mommy makeover" package.

PMID- 23158387
TI  - An argument for patient autonomy in elective surgery.

PMID- 23158386
TI  - Outer ear construction: is advocacy part of treatment?

PMID- 23158388
TI  - AMA Code of Medical Ethics' Opinion on Physician Advertising.

PMID- 23158389
TI  - Ethical issues in face transplantation.

PMID- 23158390
TI  - Diagnosing and treating microtia.

PMID- 23158391
TI  - Silicone breast implant litigation.

PMID- 23158392
TI  - An argument against the feasibility of taxing cosmetic surgery.

PMID- 23158394
TI  - Comic strip: mirror, mirror.

PMID- 23158393
TI  - Are cosmetic surgeons complicit in promoting suspect norms of beauty?

PMID- 23158395
TI  - Advertising cosmetic surgery.

PMID- 23158396
TI  - The genetic basis of body shape: lessons from mirror twins and high-definition
      digital photography.

PMID- 23158397
TI  - Character and the plastic surgeon.

PMID- 23158398
TI  - About the contributors.

PMID- 23158400
TI  - Recent advances in the prenatal interrogation of the human fetal genome.
AB  - The amount of genetic and genomic information obtainable from the human fetus
      during pregnancy is accelerating at an unprecedented rate. Two themes have
      dominated recent technological advances in prenatal diagnosis: interrogation of
      the fetal genome in increasingly high resolution and the development of non
      invasive methods of fetal testing using cell-free DNA in maternal plasma. These
      two areas of advancement have now converged with several recent reports of non
      invasive assessment of the entire fetal genome from maternal blood. However,
      technological progress is outpacing the ability of the healthcare providers and
      patients to incorporate these new tests into existing clinical care, and further
      complicates many of the economic and ethical dilemmas in prenatal diagnosis. This
      review summarizes recent work in this field and discusses the integration of
      these new technologies into the clinic and society.

PMID- 23158401
TI  - Data management in thrombin generation.
AB  - To obtain a thrombin generation (TG) curve from the conversion of added
      fluorogenic substrate, thrombin concentrations are to be derived from the
      observed velocity of increase of fluorescence (dF/dt). The relation between
      velocity and thrombin concentration varies during the experiment because
      substrate is consumed and because fluorescence is not linear with the
      concentration of product. Here we review the techniques that we developed to:

PMID- 23158399
TI  - Antibiotic prescription patterns in the empiric therapy of severe sepsis:
      combination of antimicrobials with different mechanisms of action reduces
      mortality.
AB  - INTRODUCTION: Although early institution of adequate antimicrobial therapy is
      lifesaving in sepsis patients, optimal antimicrobial strategy has not been
      established. Moreover, the benefit of combination therapy over monotherapy
      remains to be determined. Our aims are to describe patterns of empiric
      antimicrobial therapy in severe sepsis, assessing the impact of combination
      therapy, including antimicrobials with different mechanisms of action, on
      mortality. METHODS: This is a Spanish national multicenter study, analyzing all
      patients admitted to ICUs who received antibiotics within the first 6 hours of
      diagnosis of severe sepsis or septic shock. Antibiotic-prescription patterns in
      community-acquired infections and nosocomial infections were analyzed separately
      and compared. We compared the impact on mortality of empiric antibiotic
      treatment, including antibiotics with different mechanisms of action, termed
      different-class combination therapy (DCCT), with that of monotherapy and any
      other combination therapy possibilities (non-DCCT). RESULTS: We included 1,372
      patients, 1,022 (74.5%) of whom had community-acquired sepsis and 350 (25.5%) of
      whom had nosocomial sepsis. The most frequently prescribed antibiotic agents were
      beta-lactams (902, 65.7%) and carbapenems (345, 25.1%). DCCT was administered to
      388 patients (28.3%), whereas non-DCCT was administered to 984 (71.7%). The
      mortality rate was significantly lower in patients administered DCCTs than in
      those who were administered non-DCCTs (34% versus 40%; P = 0.042). The variables
      independently associated with mortality were age, male sex, APACHE II score, and
      community origin of the infection. DCCT was a protective factor against in
      hospital mortality (odds ratio (OR), 0.699; 95% confidence interval (CI), 0.522
      to 0.936; P = 0.016), as was urologic focus of infection (OR, 0.241; 95% CI,
      0.102 to 0.569; P = 0.001). CONCLUSIONS: beta-Lactams, including carbapenems, are
      the most frequently prescribed antibiotics in empiric therapy in patients with
      severe sepsis and septic shock. Administering a combination of antimicrobials
      with different mechanisms of action is associated with decreased mortality.

PMID- 23158402
TI  - Identifying major hemorrhage with automated data: results of the Veterans Affairs
      study to improve anticoagulation (VARIA).
AB  - INTRODUCTION: Identifying major bleeding is fundamental to assessing the outcomes
      of anticoagulation therapy. This drives the need for a credible implementation in
      automated data for the International Society of Thrombosis and Haemostasis (ISTH)
      definition of major bleeding. MATERIALS AND METHODS: We studied 102,395 patients
      who received 158,511 person-years of warfarin treatment from the Veterans Health
      Administration (VA) between 10/1/06-9/30/08. We constructed a list of ICD-9-CM
      codes of "candidate" bleeding events. Each candidate event was identified as a
      major hemorrhage if it fulfilled one of four criteria: 1) associated with death
      within 30days; 2) bleeding in a critical anatomic site; 3) associated with a
      transfusion; or 4) was coded as the event that precipitated or was responsible
      for the majority of an inpatient hospitalization. RESULTS: This definition
      classified 11,240 (15.8%) of 71, 338 candidate events as major hemorrhage.
      Typically, events more likely to be severe were retained at higher rates than
      those less likely to be severe. For example, Diverticula of Colon with Hemorrhage
      (562.12) and Hematuria (599.7) were retained 46% and 4% of the time,
      respectively. Major, intracranial, and fatal hemorrhage were identified at rates
      comparable to those found in randomized clinical trials however, higher than
      those reported in observational studies: 4.73, 1.29, and 0.41 per 100 patient
      years, respectively. CONCLUSIONS: We describe here a workable definition for
      identifying major hemorrhagic events from large automated datasets. This method
      of identifying major bleeding may have applications for quality measurement,
      quality improvement, and comparative effectiveness research.

PMID- 23158404
TI  - Eradication of Helicobacter pylori for prevention of ulcer recurrence after
      simple closure of perforated peptic ulcer: a meta-analysis of randomized
      controlled trials.
AB  - BACKGROUND: Eradication of Helicobacter pylori has become part of the standard
      therapy for peptic ulcer. However, the role of H pylori eradication in
      perforation of peptic ulcers remains controversial. It is unclear whether
      eradication of the bacterium confers prolonged ulcer remission after simple
      repair of perforated peptic ulcer. METHODS: A systematic review and meta-analysis
      of randomized controlled trials was performed to evaluate the effects of H pylori
      eradication on prevention of ulcer recurrence after simple closure of perforated
      peptic ulcers. The primary outcome to evaluate these effects was the incidence of
      postoperative ulcers; the secondary outcome was the rate of H pylori elimination.
      RESULTS: The meta-analysis included five randomized controlled trials and 401
      patients. A high prevalence of H pylori infection occurred in patients with
      perforated peptic ulcers. Eradication of H pylori significantly reduced the
      incidence of ulcer recurrence at 8 wk (risk ratio 2.97; 95% confidence interval:
      1.06-8.29) and 1 y (risk ratio 1.49; 95% confidence interval: 1.10-2.03)
      postoperation. The rate of H pylori eradication was significantly higher in the
      treatment group than in the nontreatment group. CONCLUSIONS: Eradication therapy
      should be provided to patients with H pylori infection after simple closure of
      perforated gastroduodenal ulcers.

PMID- 23158403
TI  - Intestinal alkaline phosphatase prevents the systemic inflammatory response
      associated with necrotizing enterocolitis.
AB  - BACKGROUND: Necrotizing enterocolitis (NEC) is the most common surgical emergency
      in neonates, with an incidence of 0.5-2.4 cases per 1000 live births and a
      mortality rate between 10% and 50%. Neonates affected by NEC develop a septic
      injury that is associated with increased risk of neurological impairment due to
      intraventricular bleeding and chronic lung disease. Intestinal alkaline
      phosphatase (IAP) is an endogenous protein that has been shown to inactivate the
      endotoxin lipopolysaccharide (LPS), and has recently been used successfully as an
      adjunct to treat sepsis in adult patients. We tested the hypothesis that
      systemic, exogenous IAP will mitigate the inflammatory response as measured by
      serum levels of proinflammatory cytokines in a rat model of NEC. METHODS: Newborn
      Sprague-Dawley rats were divided into groups. Control pups were dam fed. NEC was
      induced by feeding formula containing LPS and exposure to intermittent hypoxia.
      NEC pups were given intraperitoneal injections of 4 or 40 glycine units (U) of
      IAP or placebo twice daily. Intestine and serum was collected for cytokine
      analysis as well as measurement of alkaline phosphatase activity. RESULTS:
      Systemic IAP administration significantly increased serum alkaline phosphatase
      activity in a dose- and time-dependent fashion. The proinflammatory cytokines
      tumor necrosis factor alpha, interleukin 6, and interleukin 1beta were
      significantly increased in NEC rats versus controls on days 2 and 3. Importantly,
      treatment with 40 U systemic IAP decreased these proinflammatory cytokines back
      to near-control levels. CONCLUSIONS: Systemic IAP administration appears
      effective in mitigating the systemic inflammatory response associated with NEC,
      and may prove to be a valuable adjunctive treatment for NEC.

PMID- 23158405
TI  - Lysophospholipid variants in hepatocellular carcinoma.
AB  - BACKGROUND: The U.S. incidence of hepatocellular carcinoma (HCC) is increasing
      and is linked to hepatitis C (HepC) infection, alcohol toxicity, and obesity.
      This manuscript examines lysophosphatidic acid (LPA) variant biosynthesis as a
      biomarker and potential therapeutic target for HCC. METHODS: Serum LPA variant
      levels were determined in patients with HepC +/- HCC, alcoholic cirrhosis +/-
      HCC, or nonalcoholic steatohepatitis +/- HCC by mass spectroscopy. To clarify the
      relationship between cancer and LPA variant profiles, LPA variants were evaluated
      in HepC + HCC patients before and after liver transplantation. Moreover, LPA
      variant modification of gene expression was also determined in vitro by real-time
      polymerase chain reaction. RESULTS: In patients diagnosed with HCC, 18:2 LPA
      biosynthesis was decreased, whereas 20:4 LPA biosynthesis and 20:4 LPA:18:2 LPA
      ratio were increased. Three days after liver transplantation, serum LPA levels
      and 18:2 LPA:20:4 LPA ratio were significantly reduced in patients with cancer.
      The 20:4 LPA selectively stimulated LPA receptor and tumor necrosis factor alpha
      expression in Hep3B cells, whereas 18:2 LPA did not. CONCLUSIONS: Serum LPA
      variant profiles are unique in patients with HCC allowing for the stratification
      of patients. Moreover, LPA variants impart individual mitogenic properties
      associated with tumorigenesis that may provide a potential therapeutic target. We
      envision that LPA profiling may accelerate diagnosis, help stratify patients at
      high risk of developing cancer, and provide potential targets for
      chemoprevention.

PMID- 23158406
TI  - Modeling anesthetic times. Predictors and implications for short-term outcomes.
AB  - BACKGROUND: Little is known about the predictors of anesthetic times and impact
      of anesthetic and operative times on patient outcomes. METHODS: We documented
      operative case length, anesthetic induction time length, and anesthetic recovery
      time length in 1713 consecutive patients who underwent elective vascular surgical
      interventions. We recorded patient and procedure-related characteristics that
      might influence the anesthetic time length, including a variable for possible
      July effect. Multivariate linear regression was used to model the length of
      anesthetic times. Multivariate logistic regression was used to model the impact
      of anesthetic and operative time lengths on a composite outcome of perioperative
      (30-d postoperative) death, myocardial infarction, cardiac arrhythmias, stroke,
      and congestive heart failure. RESULTS: Statistically significant predictors of
      anesthetic induction time included body mass index, anesthesia type, and
      procedure type. Statistically significant predictors of anesthetic recovery time
      included operative case length, procedure type, and anesthesia type. After
      adjusting for the statistically significant covariates of total blood
      transfusion, history of coronary artery disease, and procedure type, there was a
      trend for increased likelihood of the composite end point as a function of
      operative time (odds ratio, 1.14; 95% confidence interval, 0.97-1.33; P = 0.09),
      which did not reach statistical significance. Multivariate analysis showed no
      association between the anesthetic time and composite end point. CONCLUSIONS:
      Modeling individually anesthetic induction and recovery time on the basis of
      operative and anesthetic procedure characteristics is feasible. Anesthetic and
      operative times do not impact perioperative morbidity and mortality.

PMID- 23158407
TI  - Endotoxin-induced changes in phospholipid dynamics of the stomach.
AB  - BACKGROUND: The gastric mucosa is protected in part by a hydrophobic layer of
      phosphatidylcholine (PC) that overlies the mucus gel on the stomach. Endotoxin
      treatment (i.e., lipopolysaccharide [LPS]) results in an apparent disruption of
      this layer, as evidenced by a reduction in surface hydrophobicity and an increase
      in transmural permeability. The current studies compared PC and lyso-PC levels in
      mucus and gastric mucosa before and after LPS treatment, and examined potential
      mechanisms for surface phospholipid changes. METHODS: Rats were administered LPS
      (5 mg//kg, intraperitoneally) and samples were collected after 5 h for analysis
      of PC and its primary degradant, lyso-PC, in the loosely and firmly adherent
      mucus layers and the mucosa. The dependence of LPS-induced effects on gastric
      alkalinization, PC synthetic activity, and intestinal reflux material was
      assessed. RESULTS: The gastric contents after LPS, which also contained duodenal
      reflux material, had greatly increased amounts of PC and lyso-PC. The firmly
      adherent mucus layer was unchanged. The gastric mucosa after LPS revealed
      significant reductions of PC levels and no change in lyso-PC content. These
      phospholipid changes were not caused by alkalinization of the stomach or altered
      PC synthesis. Prevention of duodenogastric reflux by pylorus ligation blocked the
      LPS-induced increase in luminal lyso-PC and the reduction in mucosal PC.
      CONCLUSIONS: LPS appears to induce a release of PC from gastric mucosa into the
      lumen, along with degradation of PC to lyso-PC, without an effect on PC
      synthesis. Component(s) of intestinal reflux material appear to be required for
      these effects. The lowered PC levels in gastric mucosa after LPS may contribute
      to reduced barrier properties of this tissue.

PMID- 23158408
TI  - Ulinastatin improves survival of septic mice by suppressing inflammatory response
      and lymphocyte apoptosis.
AB  - BACKGROUND: Sepsis involves imbalance between the proinflammatory and
      antiinflammatory response to bacterial insults. Ulinastatin (UTI) is a serine
      protease inhibitor and reportedly exhibits antiinflammatory properties aside from
      its blocking of the protease pathway both in vitro and in vivo. This study was
      designed to investigate the potential therapeutic efficacy of UTI for sepsis.
      MATERIALS AND METHODS: Adult C57BL/6 male mice were divided into three groups:
      sham group, cecal ligation and puncture (CLP) group, and CLP + UTI group. Acute
      septic peritonitis was induced by CLP. Saline and UTI (100,000 U/kg) were
      intravenously injected 30 min after CLP in CLP and CLP + UTI groups,
      respectively. Samples were collected for further analysis 24 h after surgery.
      RESULTS: UTI administration significantly improved 7-d survival; ameliorated
      morphologic damage and weight loss in the spleen and thymus; decreased serum
      tumor necrosis factor alpha, interleukin-6, and interleukin-10 (IL-10) levels;
      increased the number of T and B cells in peripheral blood, spleen, and thymus;
      and inhibited T-cell apoptosis in the thymus and spleen in septic mice.
      CONCLUSIONS: UTI exerted a protective effect against sepsis by suppressing
      inflammatory response and lymphocyte apoptosis.

PMID- 23158409
TI  - Shikonin attenuates lipopolysaccharide-induced acute lung injury in mice.
AB  - BACKGROUND: Shikonin, a natural naphthoquinone pigment extracted from the root of
      Lithospermum erythrorhizon, has shown a variety of pharmacologic properties
      including anti-inflammatory effect. In the present study, we analyzed the role of
      shikonin in acute lung injury induced by lipopolysaccharide (LPS) in mice.
      MATERIALS AND METHODS: Sixty male BALB/C mice were randomly allocated into six
      groups (n = 10, each): control group, shikonin group (50 mg/kg), LPS group, and
      three different doses (12.5, 25, and 50 mg/kg) for shikonin-treated groups.
      Shikonin or vehicle was given with an intragastric administration 1 h before an
      intratracheal instillation of LPS (5 mg/kg). The severity of pulmonary injury was
      evaluated 6 h after LPS challenge. RESULTS: Shikonin pretreatment significantly
      attenuated LPS-induced pulmonary histopathologic changes, alveolar hemorrhage,
      and neutrophil infiltration. The lung wet-to-dry weight ratios, as the index of
      pulmonary edema, were markedly decreased by shikonin pretreatment. Moreover,
      shikonin decreased the productions of the proinflammatory cytokines including
      tumor necrosis factor alpha and interleukin 1beta and the concentration of total
      proteins in the bronchoalveolar lavage fluid. Shikonin pretreatment also reduced
      the concentrations of myeloperoxidase and nitric oxide in lung tissues. In
      addition, shikonin pretreatment significantly suppressed LPS-induced activation
      of cyclooxygenase 2 and inducible nitric oxide synthase and the nuclear factor
      kappaB DNA-binding activity in lung tissues. CONCLUSIONS: This study indicates
      that shikonin may have a protective effect against LPS-induced acute lung injury,
      and the potential mechanism of this action may attribute partly to the inhibition
      of inducible nitric oxide synthase and cyclooxygenase 2 expression by
      downregulating nuclear factor kappaB activation.

PMID- 23158410
TI  - Climatic, ecological and socioeconomic factors as predictors of Sindbis virus
      infections in Finland.
AB  - Mosquito-borne Sindbis virus (SINV) causes rash-arthritis syndrome in Finland.
      Major outbreaks with approximately 7-year cycles have caused substantial burden
      of illness. Forest dwelling grouse are suspected to be amplifying hosts, with the
      infection transmitted to humans by mosquito bites. SINV infection surveillance
      data for 1984-2010 were used to create a negative binomial hurdle model, with
      seasonality, long-term cycles, climatic, ecological and socioeconomic variables.
      Climatic factors during early summer and amount of snow in April described the
      occurrence and incidence of SINV infections. Regulated water shore and hatch-year
      black grouse density described the occurrence, while population working in
      agriculture, agricultural land(negative) and income (negative) described the
      incidence of the disease. The prediction for 2009 was 85 cases (95% prediction
      interval 2-1187), while the actual occurrence was 106. We identified novel and
      known risk factors. The prevention of SINV infections in regulated water areas by
      infected mosquito populations should be targeted.

PMID- 23158411
TI  - Foreword.

PMID- 23158413
TI  - Targeted biopsy in the detection of prostate cancer using an office based
      magnetic resonance ultrasound fusion device.
AB  - PURPOSE: Targeted biopsy of lesions identified on magnetic resonance imaging may
      enhance the detection of clinically relevant prostate cancers. We evaluated
      prostate cancer detection rates in 171 consecutive men using magnetic resonance
      ultrasound fusion prostate biopsy. MATERIALS AND METHODS: Subjects underwent
      targeted biopsy for active surveillance (106) or persistently increased prostate
      specific antigen but negative prior conventional biopsy (65). Before biopsy, each
      man underwent multiparametric magnetic resonance imaging at 3.0 Tesla. Lesions on
      magnetic resonance imaging were outlined in 3 dimensions and assigned increasing
      cancer suspicion levels (image grade 1 to 5) by a uroradiologist. A biopsy
      tracking system was used to fuse the stored magnetic resonance imaging with real
      time ultrasound, generating a 3-dimensional prostate model on the fly. Working
      from the 3-dimensional model, transrectal biopsy of target lesions and 12
      systematic biopsies were performed with the patient under local anesthesia in the
      clinic. RESULTS: A total of 171 subjects (median age 65 years) underwent targeted
      biopsy. At biopsy, median prostate specific antigen was 4.9 ng/ml and prostate
      volume was 48 cc. A targeted biopsy was 3 times more likely to identify cancer
      than a systematic biopsy (21% vs 7%). Prostate cancer was found in 53% of men,
      38% of whom had Gleason grade 7 or greater cancer. Of the men with Gleason 7 or
      greater cancer 38% had disease detected only on targeted biopsies. Targeted
      biopsy findings correlated with level of suspicion on magnetic resonance imaging.
      Of 16 men 15 (94%) with an image grade 5 target (highest suspicion) had prostate
      cancer, including 7 with Gleason 7 or greater cancer. CONCLUSIONS: Prostate
      lesions identified on magnetic resonance imaging can be accurately targeted using
      magnetic resonance ultrasound fusion biopsy by a urologist in clinic. Biopsy
      findings correlate with level of suspicion on magnetic resonance imaging.

PMID- 23158415
TI  - Editorial comment.

PMID- 23158414
TI  - Editorial comment.

PMID- 23158416
TI  - Assessment of dental caries predictors in 6-year-old school children - results
      from 5-year retrospective cohort study.
AB  - BACKGROUND: This was a retrospective cohort study undertaken to assess the rate
      and pattern of dental caries development in 6-year-old school children followed
      up for a period of 5 years, and to identify baseline risk factors that were
      associated with 5 years caries experience in Malaysian children. METHODS: This 5
      years retrospective cohort study comprised primary school children initially aged
      6 years in 2004. Caries experience of each child was recorded annually using
      World Health Organization criteria. The rates of dental caries were recorded in
      prevalence and incidence density of carious lesions from baseline to final
      examination. Risk assessment was done to assess relative risk for caries after 5
      years in children with baseline caries status. Simple and multiple logistic
      regression analysis were performed to identify significant independent risk
      factors for caries. RESULTS: The sample consisted of 1830 school children. All
      components of DMFT showed significant differences between baseline and final
      examination. Filled teeth (FT) component of the DMFT showed the greatest
      increases. Results revealed the initial baseline caries level in permanent
      dentition was a strong predictor for future caries after 5 years (RR=3.78, 95%
      CI=3.48-4.10, P<0.001). Logistic regression analysis showed significant
      association between caries occurrence and residence (urban/rural) (OR=1.80,
      P<0.001). However, it was not significantly associated with gender and ethnicity.
      The incidence density of caries, affected persons (IDp) observed from baseline
      and after 5 years was 5.80 persons/100 person-year of observation. The rate of
      new caries-affected tooth (IDt) in the period from baseline and after 5-years was
      0.76 teeth/100 teeth-year of observation. CONCLUSION: The majority of 12-year-old
      school children (70%) were caries-free and most of the caries were concentrated
      in only a small proportion (30%) of them. We found that the presence of caries in
      permanent teeth at the age of 6 years was a strong predictor of future caries
      development in this population. The strong evidence of early permanent teeth
      caries at six years old to predict future caries incidence at 12-year-olds, which
      could be obtained at almost no cost, questions the need for and cost
      effectiveness of expensive technology-based commercial caries predictions kits.

PMID- 23158417
TI  - Vision Research special issue on "Visual attention".

PMID- 23158412
TI  - Sex and gender differences in myocarditis and dilated cardiomyopathy.
AB  - Heart failure due to nonischemic dilated cardiomyopathy (DCM) contributes
      significantly to the global burden of cardiovascular disease. Myocarditis is, in
      turn, a major cause of acute DCM in both men and women. However, recent clinical
      and experimental evidence suggests that the pathogenesis and prognosis of DCM
      differ between the sexes. This seminar provides a contemporary perspective on the
      immune mediators of myocarditis, including interdependent elements of the innate
      and adaptive immune response. The heart's acute response to injury is influenced
      by sex hormones that appear to determine the subsequent risk of chronic DCM.
      Preliminary data suggest additional genetic variations may account for some of
      the differences in epidemiology, left ventricular recovery, and survival between
      men and women. We highlight the gaps in our knowledge regarding the management of
      women with acute DCM and discuss emerging therapies, including bromocriptine for
      the treatment of peripartum cardiomyopathy.

PMID- 23158418
TI  - [Bridge between clinical guidelines and practice for stroke: stroke care quality
      control].

PMID- 23158419
TI  - [The clinical importance and heterogeneity of white matter hyperintensities].

PMID- 23158420
TI  - [Potential clinical applications of high-resolution MR imaging in intracranial
      atherosclerotic disease].

PMID- 23158421
TI  - [One-stop multi-mode computed tomography in the diagnosis and management of acute
      intracerebral hemorrhage].

PMID- 23158422
TI  - [Surfactant proteins-A and D as important serum markers for interstitial lung
      disease in patients with polymyositis or dermatomyositis].
AB  - OBJECTIVE: To explore the possible diagnostic values of serum surfactant protein
      A (SP-A) and surfactant protein-D (SP-D) for interstitial lung diseases (ILD) in
      patients with polymyositis or dermatomyositis (PM/DM). METHODS: Serum MCP-1
      concentrations were measured by enzyme-linked immunosorbent assay (ELISA) in 100
      adult PM/DM patients, 20 patients with pulmonary infection and 42 healthy
      controls. And the association with their clinical features and serum levels of SP
      A and SP-D was analyzed. RESULTS: The serum levels of SP-A and SP-D in the PM/DM
      patients with ILD were both significantly higher than those without ILD and
      healthy controls (all P < 0.01) while there were no significance differences with
      those with infectious lung diseases (P > 0.05). The sensitivity of serum abnormal
      levels of SP-A, SP-D and combination of SP-A and SP-D for ILD in PM/DM patients
      were 66.1%, 64.3% and 80.0% and the specificity 72.7%, 72.7% and 70.2%
      respectively. The serum levels of SP-A were positively correlated with serum
      ferritin and C-reactive protein (CRP) and negatively with percent carbon monoxide
      diffusing capacity (DLCO%) (r = -0.474, P < 0.05), VC% (r = -0.404, P < 0.05)
      while the serum levels of SP-D were negatively correlated with circulating CD3+T
      cells (r = -0.244, P < 0.05) and CD4+T cells (r = -0.277, P < 0.05) in PM/DM
      patients. Furthermore, SP-A was an independent risk factor for death of ILD in
      PM/DM (OR 1.032, 95%CI 1.006 - 1.059, P < 0.05). CONCLUSION: SP-A and SP-D may be
      potential useful serum markers for the diagnosis of ILD in PM/DM patients. And
      the combined detection of SP-A and SP-D offers a higher sensitivity than either
      marker alone. As a risk factor, serum SP-A can predict the prognosis of PM/DM
      patients with ILD.

PMID- 23158423
TI  - [Optimization of scan protocol in pulmonary angiography of second generation dual
      source computed tomography].
AB  - OBJECTIVE: To explore the scan protocol of second generation dual source computed
      tomography (CT) for CT pulmonary angiogram (CTPA) in patients with suspected
      pulmonary embolism and determine the proper volume of contrast medium. METHODS: A
      total of 120 patients undergoing CTPA were recruited. All examinations were
      performed on a second generation dual source CT. The scan delay was determined
      with the test bolus technique. Four contrast volume protocols were designed,
      namely groups A, B, C and D respectively (n = 30 each). For CTPA scan of groups
      A, B, C and D, 35, 40, 45 and 50 ml contrast medium were injected at an injection
      rate of 4 ml/s, followed by a saline chaser of 55, 50, 45 and 40 ml respectively.
      Attenuation profiles of different vascular segments (subclavian vein, vena cava,
      left atrium, pulmonary trunk, S1 artery, S10 artery) were measured to evaluate
      the timing techniques. The image quality and artifact of iodine map were analyzed
      by two radiologists for comparisons. RESULTS: The percentage of pulmonary
      arteries exceeding optimal attenuation (> 200 HU) showed that groups of B, C and
      D were higher than group A (93% - 100% vs 80% - 90%). The image quality of group
      A was lower than the others (P < 0.05) while the other groups showed no
      significant difference. The artifacts of iodine map of group A were much fewer
      than the others (P < 0.05) and group D was much more than the other groups (P <
      0.05). Groups B and C had a score of 4.13 and 3.67 respectively without
      significant difference (P = 0.091). CONCLUSION: With the aids of test bolus
      technique and proper injection protocol (40 ml contrast medium followed by 50 ml
      saline), the high quality image and low volume of iodine can be realized with
      second generation dual source CT for CTPA.

PMID- 23158424
TI  - [Comprehensive analysis of therapeutic methods and effect on cesarean scar
      pregnancy].
AB  - OBJECTIVE: To evaluate the efficacies and medic economic efficiency of
      therapeutic method for cesarean scar pregnancy (CSP). METHODS: The pertinent
      literatures on the treatment of CSP were collected and screened by retrieving
      some Chinese and English databases, such as PubMed, VIP and Wanfang Data. The
      weighting means and polled standard deviations of operative duration, operative
      hemorrhage volume, hysterectomy rate, length of stay, medical fees and the time
      of serum level of beta-human chorionic gonadotropin (beta-HCG) returning to
      normal were reckoned. RESULTS: Among different therapeutic methods of CSP,
      curettage duration was shortest in the patients with methotrexate (MTX)
      injection; operative hemorrhage volume, hysterectomy rate and length of stay were
      smallest in those with uterine artery embolization; medical fees was least in
      those with local MTX injection; the time of serum beta-HCG level returning to
      normal was shortest in those with hysteroscopic and/or laparoscopic operation
      after MTX injection or uterine artery embolization. CONCLUSION: Curettage after
      uterine artery embolization offers multiple advantages over therapeutic methods
      in the treatment of CSP.

PMID- 23158425
TI  - [Effects of preloading epidural space with epinephrine (1:200 000) on the
      incidence of vascular injuries through the insertion of an epidural catheter
      during cesarean section].
AB  - OBJECTIVE: To evaluate the effects of preloading epidural space with epinephrine
      (1:200 000) on the incidence of vascular injuries through the insertion of an
      epidural catheter during cesarean section. METHODS: Between May 2011 and December
      2011, upon obtaining institutional ethics approval and informed consent from the
      Human Ethics Committee of Nanjing Medical University, 100 laboring women with
      singleton cephalic presentation at term, ASA (American Society of
      Anesthesiologists) class I-II, undergoing caesarean section under continuous
      epidural analgesia were randomly divided into E and N groups according to a
      random digit table (n = 50 each). After an identification of epidural space, 5 ml
      of normal saline with epinephrine (1:200 000) was injected into epidural space in
      group E and 5 ml of normal saline in group N through an epidural needle. The
      syringe plunger was pressed firmly for 20 seconds to ensure a sufficient
      diffusion. For both groups, the levels of mean arterial pressure and heart rates
      were recorded prior to anesthesia (T1), 2 min after switching into a supine
      horizontal position after successful puncture (T2), the time of fetal delivery
      (T3) and when surgery was over (T4). The cases with bloody fluid in epidural
      puncture needle during puncture or epidural catheter during catheter placement,
      fresh blood in epidural catheter and bloody fluid in caudal end of epidural
      catheter during extubation were recorded. RESULTS: All hemodynamic changes were
      within the normal ranges. There were no obvious inter-group differences (P >
      0.05). No significant difference existed in the cases with bloody fluid in
      epidural needle during catheter insertion (10% vs 12%) or epidural catheter
      during catheter placement (4% vs 6%), fresh blood in epidural catheter (0% vs 0%)
      or bloody fluid in caudal end of epidural catheter during extubation (26% vs 30%)
      between the groups (P > 0.05). CONCLUSION: Preloading epidural space with
      epinephrine (1:200 000) may not lower the incidence of vascular injuries through
      the insertion of an epidural catheter during cesarean section.

PMID- 23158426
TI  - [Evaluation of graft perfusion in patients with ischemic-type of biliary lesions
      after liver transplantation].
AB  - OBJECTIVE: To investigate the value of 320-rows CT perfusion (CTP) imaging in the
      study of hepatic hemodynamic characters in ischemic-type biliary lesions (ITBL)
      after liver transplantation. METHODS: A total of 11 ITBL patients received 320
      slice CT angiography (CTA) and CTP after liver transplantation scheduled at 5-10
      min away. Four patients underwent liver biopsy While 7 patients with normal liver
      after transplantation were selected as the control group. The parameters of
      hepatic artery perfusion (HAP), portal vein perfusion (PVP), total hepatic
      perfusion (TLP) and hepatic arterial perfusion index (HPI) were measured and
      compared for all patients. And the blood perfusion characters of liver with ITBL
      after transplantation were analyzed. RESULTS: (1) In 11 ITBL patients, 3 patients
      had no vascular complications on CTA, 1 with simple hepatic artery stenosis
      (HAS), 1 with HAS and arterioportal shunt (APS), 2 with HAS and portal vein
      stenosis/right hepatic vein stenosis (PVS/RHVS), 1 with simple APS, 2 with simple
      PVS and 1 with portal vein thrombosis and cavernous transformation of portal vein
      (PVT and CTPV). And 4/11 patients underwent liver biopsy, 2 in which confirmed
      mild acute rejection and 2 confirmed biliary obstruction associated with
      ascending biliary infection.(2) HAP of the ITBL and control groups were (66 +/-
      38) and (40 +/- 8) ml*min(-1).(100 ml)(-1), PVP (128 +/- 35) and (163 +/- 21)
      ml*min(-1).(100 ml)(-1), TLP (194 +/- 58) and (203 +/- 19) ml*min(-1).(100 ml)(
      1), HPI 34% +/- 14% and 21% +/- 4% respectively. The differences in the value of
      HAP, PVP and HPI between the groups were statistically significant (P < 0.05)
      excluding TLP. CONCLUSION: Various liver perfusion abnormalities of ITBL may be
      evaluated objectively by CTP. ITBL might occurred when HAP and HPI increased with
      a decreased of PVP.

PMID- 23158427
TI  - [Correlations of angio-architectural factors with cerebral arteriovenous
      malformation hemorrhage].
AB  - OBJECTIVE: To explore the relationship between angio-architectures of cerebral
      arteriovenous malformations (AVM) and hemorrhage. METHODS: A total of 55
      consecutive surgical cases of AVM were collected in August 2010 to May 2011 at
      Beijing Tiantan Hospital. There were 34 males and 21 females with an average age
      of 32.5 years (range: 3 - 59). The initial symptoms included bleeding (n = 20),
      epilepsy (n = 21), headache (n = 7), neurological dysfunctions (n = 6) and others
      (n = 1). The relationship between size, location, type of feeding artery, type of
      draining vein, complicated venous aneurysm and hemorrhage was analyzed by single
      factor test. RESULTS: The cases of AVM fed by perforators, located in basal
      ganglia and post-cranial fossa, with small size, exclusively deep drainage and
      complicated venous aneurysm were more likely to present with hemorrhage.
      CONCLUSION: The hemorrhage of AVM is significantly correlated with many factors,
      such as the type of feeding artery, size and location of AVM, the type of
      draining vein and complicated venous aneurysm. But the number of draining vein is
      irrelevant.

PMID- 23158428
TI  - [Differential expressions of microRNA between young and senescent endothelial
      cells].
AB  - OBJECTIVE: To explore the differential expressions of microRNA (miRNA) between
      young and senescent endothelial cells. METHODS: Young and senescent aorta
      endothelial cells (EC) were isolated and cultured in young and old male C57BL/6J
      mice. Immunostaining of VIII factor was performed to identify the endothelial
      cells. The method of diphenyl tetrazolium bromide (MTT) was employed to compare
      the cell growth. Microarray was used to detect the differential expression of
      microRNA between young and senescent endothelial cells and the microarray results
      were confirmed by real-time polymerase chain reaction (PCR). The expression of
      endothelial nitric oxide synthase (eNOS) was detected by Western blot. RESULTS:
      Primarily cultured endothelial cells were confirmed by the VIII immunostaining
      factor. Senescent ECs grew more rapidly than young ECs in lower serum ex vivo.
      Excluding gender difference, miR-135a, miR-182, miR-96, miR-31, miR-126-3p and
      miR-362-5p were up-regulated over 2 folds in young ECs, and miR-335-3p and miR
      335-5p up-regulated over 2 folds in senescent ECs by miRNA microarray and RT-PCR.
      The up-regulation of miR335-3p in old ECs and the up-regulation of miR-135a, miR
      96 in the young ECs might contribute to a lower expression of eNOS in senescent
      ECs. CONCLUSION: The expression of miRNAs changes with advancing age and may
      result in differential expressions of downstream genes.

PMID- 23158429
TI  - [Correlation of cognitive impairment and Tau protein phosphorylation after
      isoflurane exposure in senile rats].
AB  - OBJECTIVE: To examine whether the isoflurane-induced spatial memory changes is
      associated with AD pathogenesis of tau protein phosphorylation. METHODS: We
      exposed 18-month-old male Sprague-Dawley rats to 1.4% isoflurane for 2 hours
      (anesthesia group, n = 31). Spatial memory was measured with the Morris water
      maze before and 2 days after anesthesia. Behavioral testing of the training group
      (n = 20), without anesthetics, was performed currently with the anesthesia group.
      The control group (n = 10) received no anesthesia or behavioral testing. We
      calculated the average escape latency of every training day for each rat. We
      divided the anesthesia group into an isoflurane-induced severe memory impairment
      group (SIG) and a no severe memory impairment group (NSIG) according to whether
      prolonged escape latency of each day after anesthesia was more than 1.96 SD of
      mean escape latency for the training group. Following behavioral testing, total
      tau protein (T-Tau), p-Tau-Thr231 (pT231), p-Tau-Ser396 (pS396), glycogen
      synthase kinase 3beta (GSK-3beta) and protein phosphatase 2A (PP2A) were
      quantified by Western blot. RESULTS: Six rats had severe post-anesthesia
      impairments. The expressions of T-Tau, pT231, pS396, GSK-3beta and PP2A in the
      SIG exhibited no differences as compared with the NSIG, training and control
      groups. CONCLUSION: Tau protein phosphorylation in hippocampus may be irrelevant
      for isoflurane-induced spatial memory impairment in senile rats.

PMID- 23158430
TI  - [The effect of ferric ion on the differentiation of osteoclast and bone
      resorption].
AB  - OBJECTIVE: To explore the effects of ferric ion on the differentiation from both
      RAW264.7 and bone marrow macrophages to osteoclast in vitro and bone resorption
      in vivo. METHODS: In the presence of 50 ng/ml receptor activator of nuclear
      factor kappa-B ligand (RANKL), RAW264.7 was treated with ferric ammonium citrate
      (FAC). The formation of osteoclast was observed by staining of tartrate-resistant
      acid phosphatase (TRAP) and the TRAP positive cell counted. The expression levels
      of TRAP, cathepsin-K, nuclear factor of activated T cells c1 (NFATc1) and
      (receptor activator of NF-kappaB) RANK were measured by reverse transcription
      polymerase chain reaction (RT-PCR).The control and iron overload groups were
      established by the intraperitoneal injection of normal saline and FAC. In vivo
      imaging system was employed to determine the bone density of femoral midportion
      and the fourth lumbar vertebra. After that, the bone marrow cells of femurs were
      used for osteoclast culture. The serum levels of ferritin, TRAP-5b, RANKL,
      osteoprotegerin (OPG) and C-terminal cross-linking telopeptide (CTX) were
      measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: Ferric ion could
      stimulate the formation of TRAP positive cells in a dose-dependent manner. The
      expression levels of TRAP, cathepsin-K and NFATc1 in the FAC treated group were
      significantly higher those of the control group (P < 0.05) while the expression
      of RANK showed no statistical difference among these groups (P = 0.967). The bone
      marrow density of femoral midportion and the fourth lumbar vertebra of the iron
      overload group decreased significantly versus the control group. The
      concentrations of ferritin, TRAP-5b, RANKL and CTX of the iron overload group
      were markedly higher than those of the control group (P < 0.05). Moreover, the
      concentration of ferritin showed a positive correlation with TRAP-5b and CTX
      respectively in the iron-overload group (r = 0.65, r = 0.76, P < 0.05). But no
      significant differences existed in the concentration of OPG for two groups (P >
      0.05). CONCLUSION: Ferric ion may enhance the differentiation of osteoclast in
      vitro as well as bone resorption in vivo.

PMID- 23158432
TI  - Key informant perceptions of youth-focussed sexual health promotion programs in
      Australia.
AB  - BACKGROUND: This paper explores key informant (KI) perceptions of the barriers to
      effective sexual health promotion programs in Australia and suggests strategies
      to overcome these barriers. Three types of sexual health promotion programs were
      explored in this study: those targeting all young people (under 30), Aboriginal
      young people, and young people from culturally and linguistically diverse (CALD)
      backgrounds. METHODS: The study utilised a qualitative approach and involved 33
      semistructured interviews with sexual health professionals involved in funding or
      delivering Australian sexual health promotion programs or working clinically with
      individuals diagnosed with sexually transmissible infections. RESULTS: Fourteen
      barriers to effective sexual health promotion programs were identified. Barriers
      included: difficulties associated with program evaluation, lack of involvement of
      the target community, the short-term nature of programs, problems with program
      resources and concerns about the content of programs. Additional barriers to
      programs targeting Aboriginal and CALD young people were also identified and
      included: a lack of cultural sensitivity; a failure to acknowledge differences in
      literacy, knowledge, and language skills; stigma and shame associated with sexual
      health; and the continued use of programs that lack inclusivity. KIs suggested
      strategies to overcome these barriers. CONCLUSION: Sexual health promotion in
      Australia suffers from several barriers that are likely to impede the
      effectiveness of programs. In particular, poor or nonexistent program evaluation
      and lack of community involvement are among the key areas of concern. It is hoped
      that the findings of this study will be useful in informing and shaping future
      Australian sexual health promotions.

PMID- 23158431
TI  - [Effects of all trans retinoic acid on the expression alterations of beta-protein
      1 in human breast cancer cell lines of MDA-MB-468 and MCF-7].
AB  - OBJECTIVE: To explore the effects of all trans retinoic acid (ATRA) on the cell
      proliferation and expression alterations of beta-protein 1 (BP1) in human breast
      cancer cells lines of MDA-MB-468 and MCF-7. METHOD: The proliferation changes
      were detected by thiazolyl blue tetrazolium bromide (MTT) after the treatment of
      ATRA. At the dose of 10(-5) mol/L ATRA, the expression of BP1 was measured by
      reverse transcription-polymerase chain reaction (RT-PCR) and immunochemistry.
      RESULTS: After the treatment of ATRA, the proliferation of cells and the
      expression of BP1 decreased. Optical density ratio (ODR) of each group decreased
      from 0.85 +/- 0.01, 0.71 +/- 0.01 to 0.75 +/- 0.02, 0.72 +/- 0.06 at 24 h, 0.55
      +/- 0.01, 0.52 +/- 0.05 at 48 h and 0.34 +/- 0.02, 0.48 +/- 0.03 at 72 h.
      Significant differences existed among different time groups (P < 0.01). The mean
      optical density (MOD) of each group decreased from 0.509 +/- 0.081, 0.826 +/-
      0.015 to 0.509 +/- 0.081, 0.826 +/- 0.015 at 24 h, 0.270 +/- 0.022, 0.641 +/-
      0.041 at 48 h and 0.145 +/- 0.019 and 0.206 +/- 0.179 at 72 h. Significant
      differences existed among different time groups (P < 0.01). CONCLUSION: ATRA can
      inhibit the proliferation and the expression of BP1 in breast cancer cells. And
      BP1 gene may become a therapeutic target for the ATRA-mediated inhibited growth
      of breast cancer cells.

PMID- 23158433
TI  - The world of LeGoo assessed: a short systematic and critical review.
AB  - It is very difficult to identify whether the use of the thermosensitive polymer
      LeGoo offers advantages over the use of clamps or clampless techniques for infra
      inguinal bypass. This issue of the journal provides much additional information
      about the use of LeGoo. We have summarised all the available evidence. In a very
      heterogeneous patient population, with heterogeneous graft type and location, the
      primary technical success rate remains high at 90% [95%CI 83-99], the 3 months
      secondary graft patency is 71 [95%CI 58-84]% and limb salvage is 78% [95%CI 68
      89]%. These promising early results need to be followed by extended follow up of
      the patients and standardised outcome reporting in the future.

PMID- 23158434
TI  - Are the poor differentially benefiting from provision of priority public health
      services? A benefit incidence analysis in Nigeria.
AB  - BACKGROUND: The paper presents evidence about the distribution of the benefits of
      public expenditures on a subset of priority public health services that are
      supposed to be provided free of charge in the public sector, using the framework
      of benefit incidence analysis. METHODS: The study took place in 2 rural and 2
      urban Local Government Areas from Enugu and Anambra states, southeast Nigeria. A
      questionnaire was used to collect data on use of the priority public health
      services by all individuals in the households (n=22,169). The level of use was
      disaggregated by socio-economic status (SES), rural-urban location and gender.
      Benefits were valued using the cost of providing the service. Net benefit
      incidence was calculated by subtracting payments made for services from the value
      of benefits. RESULTS: The results showed that 3,281 (14.8%) individuals consumed
      wholly free services. There was a greater consumption of most free services by
      rural dwellers, females and those from poorer SES quintiles (but not for
      insecticide-treated nets and ante-natal care services). High levels of payment
      were observed for immunisation services, insecticide-treated nets, anti-malarial
      medicines, antenatal care and childbirth services, all of which are supposed to
      be provided for free. The net benefits were significantly higher for the rural
      residents, males and the poor compared to the urban residents, females and better
      off quintiles. CONCLUSION: It is concluded that coverage of all of these priority
      public health services fell well below target levels, but the poorer quintiles
      and rural residents that are in greater need received more benefits, although not
      so for females. Payments for services that are supposed to be delivered free of
      charge suggests that there may have been illegal payments which probably hindered
      access to the public health services.

PMID- 23158435
TI  - Ectopic canine control with conventional brackets.
AB  - Although evident advances have certainly been made, not only in the use of
      brackets, but also in the mechanics and type of wires and accessories employed,
      the most recent systematic review of the literature on this topic stated despite
      claims regarding the clinical superiority of self-ligating brackets, evidence is
      generally lacking. Thus, the aim of this study was to show, by means of four
      clinical case reports, that conventional brackets, used in conjunction with
      relatively recently introduced thermal nickel-titanium archwires of reduced
      diameter and extremely light nickel-titanium springs, give results comparable
      with those achieved via the use of self-ligating brackets.

PMID- 23158437
TI  - An integrative review of supportive e-health programs in cancer care.
AB  - PURPOSE: This integrative review aims to gather more knowledge of the design of
      supportive e-health interventions for patients diagnosed with cancer and
      subsequently analyze and synthesize that knowledge in a potential explanatory
      model for those interventions. METHODS: PubMed, CINAHL and PsycINFO were searched
      for abstracts dating from 2000 through to June 2012. Eligible articles concerned
      education or support for adult cancer patients, and were provided either on the
      Internet or using CD-ROM or DVD. RESULTS: Twenty-eight quantitative studies
      constituted the final sample, revealing that supportive e-health programs in the
      field of cancer are being used and are helpful to individuals despite their age,
      gender, literacy level and disease-stage. Each e-health program usually
      constitutes a single service with a variety of multimedia features, which leads
      to different designs yet with common outcomes. Some of these outcomes are
      theoretically explained, although a structure that links all aspects of the
      intervention is rarely found. Moreover, different designs have also been adopted
      for testing the interventions' effectiveness. CONCLUSION: E-health interventions
      that allow supportive needs to be satisfied are leading to positive effects for
      individuals with different preferences and priorities. Even though several
      communalities could be found across interventions, methodological aspects of
      design, implementation and evaluation still vary, leading to some inconsistency.
      Models and applied theories are needed to clarify such issues, thus enhancing the
      credibility and applicability of supportive e-health programs across target
      populations.

PMID- 23158438
TI  - Ethnic and racial socialization and self-esteem of Asian adoptees: the mediating
      role of multiple identities.
AB  - Positive identity development during adolescence in general is a complex process
      and may pose additional challenges for adolescents adopted from a different
      culture. Using a web-based survey design with a sample of 100 internationally
      adopted Asian adolescent and young adults, the present study examined the
      mediating role of multiple identities (i.e., ethnic, adoptive and interpersonal
      ego identities) in explaining the relationship between ethnic and racial
      socializations, ethnic neighborhood, and self-esteem. The results showed that (a)
      adoptive identity mediated the influence of racial socialization on psychological
      well-being, and (b) ethnic affirmation mediated the influence of ethnic
      socialization on adoptees' well-being. This study illustrates the importance of
      providing supportive counseling services for adoptees who are exploring their
      adoptive identity.

PMID- 23158440
TI  - [Cystic adventitial disease of the popliteal artery].

PMID- 23158441
TI  - Keeping Ethics Alive in the ED.

PMID- 23158442
TI  - Make It OK That This Life Is Ending.

PMID- 23158443
TI  - Taking no for an answer-refusal of life-sustaining treatment.

PMID- 23158439
TI  - Notch signaling in pediatric soft tissue sarcomas.
AB  - Pediatric soft tissue sarcomas are rare tumors of childhood, frequently
      characterized by specific chromosome translocations. Despite improvements in
      treatment, their clinical management is often challenging due to the low
      responsiveness of metastatic forms and aggressive variants to conventional
      therapeutic approaches, which leads to poor overall survival. It is widely
      thought that soft tissue sarcomas derive from mesenchymal progenitor cells that,
      during embryonic life, have developed chromosomal aberrations with de-regulation
      of the main pathways governing tissue morphogenesis. The Notch signaling pathway
      is one of the most important molecular networks involved in differentiation
      processes. Emerging evidence highlights the role of Notch signaling de-regulation
      in the biology of these pediatric sarcomas. In this review, we present an outline
      of recently gathered evidence on the role of Notch signaling in soft tissue
      sarcomas, highlighting its importance in tumor cell biology. The potential
      challenges and opportunities of targeting Notch signaling in the treatment of
      pediatric soft tissue sarcomas are also discussed.

PMID- 23158444
TI  - Resource allocation shake-up.

PMID- 23158446
TI  - AMA Code of Medical Ethics' Opinion on Physician Duty to Treat.

PMID- 23158445
TI  - Preparing for the Unexpected-Teaching ER Ethics.

PMID- 23158447
TI  - Rethinking the Physician's Duty in Disaster Care.

PMID- 23158448
TI  - Disaster and mass casualty triage.

PMID- 23158449
TI  - Is EMTALA That Bad?

PMID- 23158450
TI  - Nonurgent care in the emergency department-bane or boon?

PMID- 23158451
TI  - Ending ambulance diversion in massachusetts.

PMID- 23158452
TI  - Gaps in the safety net metaphor.

PMID- 23158453
TI  - Social justice, egalitarianism, and the history of emergency medicine.

PMID- 23158454
TI  - Unwitting partners in death-the ethics of teamwork in disaster management.

PMID- 23158455
TI  - About the contributors.

PMID- 23158456
TI  - Environmental variability and the transmission of haemorrhagic fever with renal
      syndrome in Changsha, People's Republic of China.
AB  - The transmission of haemorrhagic fever with renal syndrome (HFRS) is influenced
      by climatic, reservoir and environmental variables. The epidemiology of the
      disease was studied over a 6-year period in Changsha. Variables relating to
      climate, environment, rodent host distribution and disease occurrence were
      collected monthly and analysed using a time-series adjusted Poisson regression
      model. It was found that the density of the rodent host and multivariate El Nino
      Southern Oscillation index had the greatest effect on the transmission of HFRS
      with lags of 2-6 months. However, a number of climatic and environmental factors
      played important roles in affecting the density and transmission potential of the
      rodent host population. It was concluded that the measurement of a number of
      these variables could be used in disease surveillance to give useful advance
      warning of potential disease epidemics.

PMID- 23158457
TI  - Limbic and callosal white matter changes in euthymic bipolar I disorder: an
      advanced diffusion magnetic resonance imaging tractography study.
AB  - BACKGROUND: White matter microstructural changes detected using diffusion tensor
      imaging have been reported in bipolar disorder. However, findings are
      heterogeneous, which may be related to the use of analysis techniques that cannot
      adequately model crossing fibers in the brain. We therefore sought to identify
      altered diffusion anisotropy and diffusivity changes using an improved high
      angular resolution fiber-tracking technique. METHODS: Diffusion magnetic
      resonance imaging data was obtained from 35 prospectively confirmed euthymic
      bipolar disorder type 1 patients (age 22-59) and 43 control subjects (age 22-59)
      drawn from a sample of 120 age- and gender-matched demographically similar case
      control pairs. Tractography using a constrained spherical deconvolution approach
      to account for crossing fibers was implemented. Changes in fractional anisotropy,
      mean diffusivity, axial diffusivity, and radial diffusivity between patient and
      control groups in subdivisions of the corpus callosum, cingulum, and fornix were
      measured as indicators of trait differences in white matter microstructural
      organization in bipolar disorder. RESULTS: Patients had significantly reduced
      fractional anisotropy and increased mean diffusivity and radial diffusivity in
      all divisions of the corpus callosum, left fornix, and subgenual cingulum
      compared with control subjects. Axial diffusivity was increased in the fornix
      bilaterally and right dorsal-anterior cingulum. CONCLUSIONS: By using an improved
      fiber-tracking method in a clinically homogeneous population, we were able to
      localize trait diffusivity changes to specific subdivisions of limbic fiber
      pathways, including the fornix. Our findings extend previous reports of altered
      limbic system microstructural disorganization as a trait feature of bipolar
      disorder.

PMID- 23158458
TI  - Multiple regulatory variants modulate expression of 5-hydroxytryptamine 2A
      receptors in human cortex.
AB  - BACKGROUND: The 5-hydroxytryptamine 2A receptor, encoded by HTR2A, is a major
      postsynaptic target for serotonin in the human brain and a therapeutic drug
      target. Despite hundreds of genetic associations investigating HTR2A
      polymorphisms in neuropsychiatric disorders and therapies, the role of genetic
      HTR2A variability in health and disease remains uncertain. METHODS: To discover
      and characterize regulatory HTR2A variants, we sequenced whole transcriptomes
      from 10 human brain regions with massively parallel RNA sequencing and measured
      allelic expression of multiple HTR2A messenger (m)RNA transcript variants.
      Following discovery of functional variants, we further characterized their impact
      on genetic expression in vitro. RESULTS: Three polymorphisms modulate the use of
      novel alternative exons and untranslated regions (UTRs), changing expression of
      RNA and protein. The frequent promoter variant rs6311, widely implicated in human
      neuropsychiatric disorders, decreases usage of an upstream transcription start
      site encoding a longer 5'UTR with greater translation efficiency. rs76665058,
      located in an extended 3'UTR and unique to individuals of African descent,
      modulates allelic HTR2A mRNA expression. The third single nucleotide
      polymorphism, unannotated and present in only a single subject, directs
      alternative splicing of exon 2. Targeted analysis of HTR2A in the Sequenced
      Treatment Alternatives to Relieve Depression (STAR*D) study reveals associations
      between functional variants and depression severity or citalopram response.
      CONCLUSIONS: Regulatory polymorphisms modulate HTR2A mRNA expression in an
      isoform-specific manner, directing the usage of novel untranslated regions and
      alternative exons. These results provide a foundation for delineating the role of
      HTR2A and serotonin signaling in central nervous system disorders.

PMID- 23158459
TI  - Blockade of estrogen by hormonal contraceptives impairs fear extinction in female
      rats and women.
AB  - BACKGROUND: Fear extinction is a laboratory model of fear inhibition and is the
      basis of exposure therapy for anxiety disorders. Emerging evidence from naturally
      cycling female rodents and women indicates that estrogens are necessary to the
      consolidation of fear extinction. Hormonal contraceptives (HCs) inhibit estrogen
      production; yet, their effects on fear extinction are unknown. METHODS: We used a
      cross-species translational approach to investigate the impact of HCs and
      estradiol supplementation on fear extinction in healthy women (n=76) and female
      rats (n = 140). RESULTS: Women using HCs exhibited significantly poorer
      extinction recall compared with naturally cycling women. The extinction
      impairment was also apparent in HC-treated female rats and was associated with
      reduced serum estradiol levels. The impairment could be rescued in HC-treated
      rats either by terminating HC treatment after fear learning or by systemic
      injection of estrogen-receptor agonists before fear extinction, all of which
      restored serum estradiol levels. Finally, a single administration of estradiol to
      naturally cycling women significantly enhanced their ability to recall extinction
      memories. CONCLUSIONS: Together, these findings suggest that HCs may impact
      women's ability to inhibit fear but that this impairment is not permanent and
      could potentially be alleviated with estrogen treatment.

PMID- 23158462
TI  - Diagnostic approach to cerebral aneurysms.
AB  - Cerebral aneurysms are an important cause of morbidity and mortality due to their
      causal effect in non-traumatic subarachnoid hemorrhage. Neurosurgical progress in
      the 20th century helped to improve patient outcomes greatly. In recent years,
      techniques such as intravascular treatment by coiling and/or stenting have found
      an additional place in the management of the disease. With the development of
      less and less invasive surgical and endovascular techniques, there has also been
      a continuous development in imaging techniques that have led to our current
      situation where we dispose of CT and MR techniques that can help improve
      treatment planning greatly. CT is able to detect and together with its adjunct
      techniques CT angiography and CT perfusion, it can allow us to provide the
      physicians in charge with a detailed image of the aneurysm, the feeding vessels
      as well as the status of blood flow to the brain. Angiography has evolved by
      becoming the standard tool for guidance during decision making for whatever
      therapy is being envisioned be it endovascular procedures and or surgery and has
      even progressed more recently due to the development of so-called flat panel
      technology that now allows to acquire CT-like images during and directly after an
      intervention. Thus nowadays, the diagnostic and interventional techniques and
      procedures have become so much entwined as to be considered a whole. 

PMID- 23158461
TI  - The multidrug-resistant PMEN1 pneumococcus is a paradigm for genetic success.
AB  - BACKGROUND: Streptococcus pneumoniae, also called the pneumococcus, is a major
      bacterial pathogen. Since its introduction in the 1940s, penicillin has been the
      primary treatment for pneumococcal diseases. Penicillin resistance rapidly
      increased among pneumococci over the past 30 years, and one particular multidrug
      resistant clone, PMEN1, became highly prevalent globally. We studied a collection
      of 426 pneumococci isolated between 1937 and 2007 to better understand the
      evolution of penicillin resistance within this species. RESULTS: We discovered
      that one of the earliest known penicillin-nonsusceptible pneumococci, recovered
      in 1967 from Australia, was the likely ancestor of PMEN1, since approximately 95%
      of coding sequences identified within its genome were highly similar to those of
      PMEN1. The regions of the PMEN1 genome that differed from the ancestor contained
      genes associated with antibiotic resistance, transmission and virulence. We also
      revealed that PMEN1 was uniquely promiscuous with its DNA, donating penicillin
      resistance genes and sometimes many other genes associated with antibiotic
      resistance, virulence and cell adherence to many genotypically diverse
      pneumococci. In particular, we describe two strains in which up to 10% of the
      PMEN1 genome was acquired in multiple fragments, some as long as 32 kb,
      distributed around the recipient genomes. This type of directional genetic
      promiscuity from a single clone to numerous unrelated clones has, to our
      knowledge, never before been described. CONCLUSIONS: These findings suggest that
      PMEN1 is a paradigm of genetic success both through its epidemiology and
      promiscuity. These findings also challenge the existing views about horizontal
      gene transfer among pneumococci.

PMID- 23158463
TI  - The 2008 prevalence of chiropractic use in the US adult population.
AB  - OBJECTIVE: The purpose of this study was to produce prevalence estimates and
      identify determinants of variability in chiropractic use in the US adult
      population. METHODS: The Medical Expenditure Panel Survey was used to estimate
      prevalence for the adult population and subpopulations according to several
      sociodemographic, geographic, and health characteristics. Multivariable logistic
      regression model was used to explore the effects of the independent predictors on
      chiropractic use. RESULTS: The 2008 chiropractic prevalence of use was estimated
      to be 5.2% (95% confidence interval, 4.7-5.6). The adjusted odds of using
      chiropractic services were approximately 46% less for Asians, 63% less for
      Hispanics, and 73% less for blacks compared with whites; 21% less for men than
      women; and 68% higher for those with arthritis compared with those without.
      Persons from high-income families have greater odds of using chiropractic
      services compared with those from middle-income (42%) and low-income (67%)
      families. There was a significant interaction between Census region and urban
      rural location. The results showed the prevalence of chiropractic use to be
      highest in small metro areas in the Midwest (10.5%) and Northeast (10.4%) as well
      as micropolitan/noncore areas in the West (10.8%) and Midwest (10.1%).
      CONCLUSIONS: This study validates previous findings showing the prevalence of use
      is higher for whites, women, and persons with higher family income or reported
      arthritis. The results of this study also indicate that chiropractic use varies
      across the urban-rural landscape depending on the region of the country,
      suggesting that the effect of geographic location may be more complex than
      previously reported.

PMID- 23158464
TI  - Clinical, demographic, and geographic determinants of variation in chiropractic
      episodes of care for adults using the 2005-2008 Medical Expenditure Panel Survey.
AB  - OBJECTIVE: The primary aim of this study was to report nationally representative
      estimates of the visit utilization, per visit expenditures, and total
      expenditures for chiropractic episodes of care in the US adult population. The
      secondary aim was to identify clinical, demographic, geographic, and payment
      factors associated with variation in the levels of utilization and expenditures.
      METHODS: Data from the 2005-2008 Medical Expenditure Panel Survey were used to
      construct complete episodes of chiropractic care (n = 1639) for the civilian,
      noninstitutionalized adult population. Bivariate descriptive statistics were
      calculated for visit utilization, per visit expenditures, and total expenditures
      per episode of care by several clinical, demographic, geographic, and payment
      variables. Multivariable regression models were used to evaluate the effects of
      the independent variables on each of the 3 dependent variables. RESULTS: The
      unadjusted mean number of visits per episode was 5.8 (95% confidence interval
      [CI], 5.3-6.4] and varied significantly by race/ethnicity, perceived mental
      health, urban-rural location, and source of payment. The mean total expenditures
      per visit per episode were estimated to be $69 (95% CI, $65-$73). There was
      variation associated with the census region, urban-rural location, and source of
      payment variables. Total expenditures for an episode of care were estimated to be
      $424 (95% CI, $371-$477] with variation according to urban-rural location and
      source of payment. During 29% of the episodes all expenditures were paid with out
      of-pocket funds. CONCLUSIONS: Variation in the utilization and expenditures
      during chiropractic episodes of care is primarily associated with payment source
      and geographic factors.

PMID- 23158465
TI  - Efficacy of chiropractic manual therapy on infant colic: a pragmatic single
      blind, randomized controlled trial.
AB  - OBJECTIVE: The purpose of this study was to determine the efficacy of
      chiropractic manual therapy for infants with unexplained crying behavior and if
      there was any effect of parental reporting bias. METHODS: Infants with
      unexplained persistent crying (infant colic) were recruited between October 2007
      and November 2009 at a chiropractic teaching clinic in the United Kingdom.
      Infants younger than 8 weeks were randomized to 1 of 3 groups: (i) infant
      treated, parent aware; (ii) infant treated, parent unaware; and (iii) infant not
      treated, parent unaware. The primary outcome was a daily crying diary completed
      by parents over a period of 10 days. Treatments were pragmatic, individualized to
      examination findings, and consisted of chiropractic manual therapy of the spine.
      Analysis of covariance was used to investigate differences between groups.
      RESULTS: One hundred four patients were randomized. In parents blinded to
      treatment allocation, using 2 or less hours of crying per day to determine a
      clinically significant improvement in crying time, the increased odds of
      improvement in treated infants compared with those not receiving treatment were
      statistically significant at day 8 (adjusted odds ratio [OR], 8.1; 95% confidence
      interval [CI], 1.4-45.0) and at day 10 (adjusted OR, 11.8; 95% CI, 2.1-68.3). The
      number needed to treat was 3. In contrast, the odds of improvement in treated
      infants were not significantly different in blinded compared with nonblinded
      parents (adjusted ORs, 0.7 [95% CI, 0.2-2.0] and 0.5 [95% CI, 0.1-1.6] at days 8
      and 10, respectively). CONCLUSIONS: In this study, chiropractic manual therapy
      improved crying behavior in infants with colic. The findings showed that
      knowledge of treatment by the parent did not appear to contribute to the observed
      treatment effects in this study. Thus, it is unlikely that observed treatment
      effect is due to bias on the part of the reporting parent.

PMID- 23158466
TI  - Myofascial trigger points, pain, disability, and sleep quality in individuals
      with mechanical neck pain.
AB  - OBJECTIVE: The purpose of this study was to investigate the presence of active
      myofascial trigger points (MTrPs) in a greater number of muscles than previous
      studies and the relation between the presence of MTrPs, the intensity of pain,
      disability, and sleep quality in mechanical neck pain. METHODS: Fifteen patients
      with mechanical neck pain (80% women) and 12 comparable controls participated.
      Myofascial trigger points were bilaterally explored in the upper trapezius,
      splenius capitis, semispinalis capitis, sternocleidomastoid, levator scapulae,
      and scalene muscles in a blinded design. Myofascial trigger points were
      considered active if the subject recognized the elicited referred pain as a
      familiar symptom. Myofascial trigger points were considered latent if the
      elicited referred pain was not recognized as a symptom. Pain was collected with a
      numerical pain rate scale (0-10); disability was assessed with Neck Disability
      Index; and sleep quality, with the Pittsburgh Sleep Quality Index. RESULTS:
      Patients exhibited a greater disability and worse sleep quality than controls (P
      < .001). The Pittsburgh Sleep Quality Index score was associated with the worst
      intensity of pain (r = 0.589; P = .021) and disability (r = 0.552; P = .033).
      Patients showed a greater (P = .002) number of active MTrPs (mean, 2 +/- 2) and
      similar number (P = .505) of latent MTrPs (1.6 +/- 1.4) than controls (latent
      MTrPs, 1.3 +/- 1.4). No significant association between the number of latent or
      active MTrPs and pain, disability, or sleep quality was found. CONCLUSIONS: The
      referred pain elicited by active MTrPs in the neck and shoulder muscles
      contributed to symptoms in mechanical neck pain. Patients exhibited higher
      disability and worse sleep quality than controls. Sleep quality was associated
      with pain intensity and disability. No association between active MTrPs and the
      intensity of pain, disability, or sleep quality was found.

PMID- 23158467
TI  - Prevalence of modic changes in active duty military men with lumbar disk
      herniation who were scheduled for surgery.
AB  - OBJECTIVE: The purpose of this study was to report on the prevalence of Modic
      changes (MCs) in a group of Netherlands military men who were scheduled for
      surgery (lumbar discectomy). METHODS: This was a retrospective observational
      study of health records. From 133 patients in active military service seen from
      January 2004 to March, 77 case files were selected. For all subjects who met
      inclusion criteria, the health records and T1- and T2-weighted magnetic resonance
      imaging files of lumbar levels L4/L5 and L5-S1 were assessed. Data including age,
      sex, rank in military, level of lumbar herniation, and level of MC including
      their types were evaluated. RESULTS: Nineteen subjects (24.7%) showed presence of
      MC at the level of disk herniation, 5 subjects (6.5%) showed MC at a different
      level, and 10 subjects (13%) showed MC at both levels. In total, 154 segments
      were analyzed on magnetic resonance imaging for present MC of which 44 levels
      (28.6%) showed MC type I (31.8%), type II (65.9%), or type III (2.3%). Higher age
      showed to be significant (P <= .001) on developing MC, but no significance was
      found for physical workload in relation to these changes. CONCLUSIONS: For the
      subjects in this study, MCs were most common at the lower lumbar spine segments,
      with a predominance of type II. In this study, the presence of a disk herniation
      and MC at the same level was 37.7%; however, a significant association was not
      demonstrable.

PMID- 23158468
TI  - Evaluating serratus anterior muscle function in neck pain using muscle functional
      magnetic resonance imaging.
AB  - OBJECTIVE: Muscle functional magnetic resonance imaging (mfMRI) quantifies
      exercise-induced alterations in soft-aqueous skeletal muscle as a surrogate
      measure of muscle activity. Because of its excellent spatiotemporal resolution,
      mfMRI can be used as a noninvasive evaluation of the function of muscles that are
      challenging to evaluate, such as the serratus anterior (SA) muscle. The purpose
      of this preliminary study was to investigate the feasibility of evaluating SA
      muscle function in individuals with neck pain compared with healthy controls
      using mfMRI. METHODS: Muscle functional magnetic resonance imaging scans of the
      SA muscle were obtained before and immediately after an isometric upper limb
      exercise in 10 subjects with chronic ipsilateral mechanical neck pain and
      scapular dysfunction (scan on symptomatic side) and in 10 age- and sex-matched
      healthy subjects. Scans were recorded at 4 intervertebral levels (T6-7, T7-8, T8
      9, and T9-10). Differences in water relaxation values (T2 relaxation) quantified
      from scans before and after exercise were calculated (T2 shift) as a measure of
      SA muscle activity at each level and compared between groups. RESULTS: There were
      significant effects for level (P = .03) and significant group * level
      interactions (P = .04) but no significant main effect for group (P = .59). Post
      hoc tests revealed that significant differences in T2 shift values between levels
      were only evident in the healthy control group. CONCLUSIONS: This study
      demonstrated that despite some inherent challenges associated with imaging the SA
      muscle, mfMRI appears to have adequate spatiotemporal resolution to effectively
      evaluate SA muscle activity and function in healthy and clinical populations.

PMID- 23158469
TI  - Reliability and measurement error of 3-dimensional regional lumbar motion
      measures: a systematic review.
AB  - OBJECTIVE: The purpose of this study was to systematically review the literature
      on reproducibility (reliability and/or measurement error) of 3-dimensional (3D)
      regional lumbar motion measurement systems. METHODS: Electronic searches were
      performed in PubMed, Cumulative Index of the Nursing and Allied Health
      Literature, Embase, and Mantis databases. To be included, original studies had to
      report on the reproducibility of a 3D computerized regional lumbar spinal motion
      analysis system in human subjects. A detailed checklist was developed based on
      guidelines for reporting reliability and agreement studies, the standards for
      reporting of diagnostic accuracy, and quality assessment of diagnostic accuracy
      studies and used for data extraction and quality assessment. The checklist
      consisted of descriptive items divided into 4 domains: study population, testing
      circumstances, equipment, and data analysis and presentation. The descriptive
      items were used as foundation for the quality assessment reflecting the reporting
      level of the included articles. RESULTS: A total of 15 articles were included in
      this study. We found incomplete reporting in 1 or more domains in all articles. A
      varying amount of measurement error was reported in 8 of the 15 articles. Because
      of incomplete reporting, these reliability and measurement error estimates are
      difficult to interpret. CONCLUSIONS: The current literature on the reliability
      and measurement error of measures created by regional 3D spinal instruments
      contains uncertainties especially in relevant clinical populations. There is
      uncertainty with respect to the degree that repeated measurements by 3D regional
      spinal motion instruments are reproducible. However, limited to the studies where
      reliability estimates were provided, most instruments used under standardized
      conditions may be considered reliable enough to be used for research purposes on
      the group level, but it is uncertain if they can be used on the individual
      patient level.

PMID- 23158471
TI  - Evaluation of mechanical allodynia in an animal immobilization model using the
      Von Frey method.

PMID- 23158472
TI  - Penile carcinoma: lessons learned from vulvar carcinoma.
AB  - PURPOSE: Penile carcinoma is rare in the developed world and treatment guidelines
      are often based on marginal clinical data. Prospective controlled studies are
      virtually absent and meta-analyses are rare. Vulvar carcinoma, on the other hand,
      has many parallels to penile carcinoma, and the level of evidence for diagnosis
      and treatment is more robust. Therefore, we assessed the body of literature on
      vulvar carcinoma to identify potential improvements in the care of patients with
      penile carcinoma. MATERIALS AND METHODS: A literature review was performed on
      vulvar carcinoma and direct comparisons were made to a similar review of the
      literature on penile carcinoma. RESULTS: Several aspects of vulvar carcinoma
      management are clearly established and deserve closer evaluation in penile
      carcinoma. For example, human papillomavirus is identified in a high percentage
      of patients with vulvar carcinoma but is understudied in penile carcinoma.
      Further study is of potential clinical value, especially with the development of
      human papillomavirus vaccines for prevention. Penile carcinoma TNM staging does
      not adequately stratify survival or risk of advanced disease. Staging of vulvar
      carcinoma is dependent on tumor size and depth of invasion measured in
      millimeters, as opposed to the invasion of underlying structures in penile
      carcinoma. Management of the inguinal nodes is more refined for vulvar carcinoma,
      where lymphatic mapping has been conducted and sentinel node biopsy has proven to
      be highly effective in multicenter trials. Finally, the efficacy of adjuvant
      radiation and chemotherapy has been tested in controlled trials or reported in
      meta-analyses for vulvar carcinoma, which are both lacking for penile carcinoma.
      Radiation after inguinal node dissection, for example, has been shown to enhance
      survival in patients with defined risk factors. Neoadjuvant chemoradiation is
      recommended before surgery for advanced vulvar carcinoma. CONCLUSIONS: Evidence
      derived from studies on vulvar carcinoma can be extrapolated to penile carcinoma
      to help guide clinical trials and future research directions to enhance the
      treatment of these patients.

PMID- 23158474
TI  - Demand for HIV clinical services is increasing in Australia but supply is
      decreasing.
AB  - BACKGROUND: HIV clinical service planning requires accurate estimates of the
      number of people living with HIV (PLHIV) and the capacity of existing clinical
      services, each by geographical location. The aim of this study was to quantify
      current HIV clinical service capacity in Australia. METHODS: This study was a
      retrospective analysis of records of HIV clinical service capacity in Australia.
      Participants were general practitioners who completed an annual survey in 2007
      2009. Information on the number of hospital departments, sexual health services,
      antiretroviral-prescribing general practitioners (ARV-GPs) and shared-care
      services providing expertise in HIV management from 2007 to 2010 were also
      available. RESULTS: From 2007 to 2009, the proportion of ARV-GP survey
      respondents treating 2-9 patients with HIV per week increased from 36.5% to
      49.1%, with a corresponding decrease in the average proportion who saw less than
      one patient with HIV per week. The estimated number of PLHIV has increased by
      12.5% in metropolitan areas, and 16.5% in rural and remote areas over the period
      2007-2010; however, the total number of services with at least one HIV ARV-GP has
      decreased over the same period. CONCLUSIONS: Current methods to estimate clinical
      service capacity reveal decreasing supply in the workforce in Australia despite
      increasing numbers of PLHIV. Further training of HIV clinicians and their
      placement in regions of greatest supply-demand deficits are required. Further
      studies are required to precisely quantify and locate the capacity of the HIV
      clinical workforce with expertise in HIV case-management to enable efficient
      service planning.

PMID- 23158473
TI  - Ovarian cancer ascites increase Mcl-1 expression in tumor cells through ERK1/2
      Elk-1 signaling to attenuate TRAIL-induced apoptosis.
AB  - BACKGROUND: Ascites may affect the progression of ovarian cancer (OC). In
      particular, soluble factors present in OC ascites can create a protective
      environment for tumor cells that promote de novo resistance to drug- and death
      receptor-induced apoptosis. However, the underlying molecular mechanisms
      responsible for ascites-induced drug resistance are not well characterized.
      METHODS: Using human OC cell lines and tissues microarrays of human OC biopsies,
      we assessed the mechanism by which OC ascites increase Mcl-1 expression using
      Western blots, chemical inhibitors of ERK and small-inhibitory RNA treatments.
      RESULTS: In the present study, we found that both Mcl-1 mRNA and protein levels
      were upregulated within 2 h upon treatment of OC cells with ascites obtained from
      women with advanced OC. In contrast, the expression of other Bcl-2 family
      antiapoptotic members such as Bcl-2 and Bcl-XL was not affected by ascites. An
      increase of Mcl-1 expression was consistently observed across different ascites
      from women with advanced serous OC. The knockdown of Mcl-1 significantly blocked
      ascites-induced Mcl-1 upregulation and ascites-mediated inhibition of TRAIL
      induced apoptosis. Ascites induced a rapid phosphorylation of ERK1/2 and Elk-1
      transcription factor. Furthermore, we found that ERK1/2 inhibition or Elk-1
      knockdown was sufficient to block ascites-induced Mcl-1 expression. In high grade
      serous OC, we found a positive correlation between phosphorylated ERK1/2 and Mcl
      1 expression. CONCLUSIONS: These results indicate that ascites-induced ERK1/2/Elk
      1 signaling is critical for Mcl-1 expression and for the ascites-mediated
      attenuation of TRAIL-induced apoptosis. The ERK1/2/Elk-1/Mcl-1 pathway represents
      a novel mechanism by which ascites induce de novo TRAIL resistance in OC cells.

PMID- 23158475
TI  - Out-of-pocket healthcare payments on chronic conditions impoverish urban poor in
      Bangalore, India.
AB  - BACKGROUND: The burden of chronic conditions is on the rise in India,
      necessitating long-term support from healthcare services. Healthcare, in India,
      is primarily financed through out-of-pocket payments by households. Considering
      scarce evidence available from India, our study investigates whether and how out
      of-pocket payments for outpatient care affect individuals with chronic
      conditions. METHODS: A large census covering 9299 households was conducted in
      Bangalore, India. Of these, 3202 households that reported presence of chronic
      condition were further analysed. Data was collected using a structured household
      level questionnaire. Out-of-pocket payments, catastrophic healthcare expenditure,
      and the resultant impoverishment were measured using a standard technique.
      RESULTS: The response rate for the census was 98.5%. Overall, 69.6% (95%CI=68.0
      71.2) of households made out-of-pocket payments for outpatient care spending a
      median of 3.2% (95%CI=3.0-3.4) of their total income. Overall, 16% (95%CI=14.8
      17.3) of households suffered financial catastrophe by spending more than 10% of
      household income on outpatient care. Occurrence and intensity of financial
      catastrophe were inequitably high among poor. Low household income, use of
      referral hospitals as place for consultation, and small household size were
      associated with a greater likelihood of incurring financial catastrophe.The out
      of-pocket spending on chronic conditions doubled the number of people living
      below the poverty line in one month, with further deepening of their poverty. In
      order to cope, households borrowed money (4.2% instances), and sold or mortgaged
      their assets (0.4% instances). CONCLUSIONS: This study provides evidence from
      India that the out-of-pocket payment for chronic conditions, even for outpatient
      care, pushes people into poverty. Our findings suggest that improving
      availability of affordable medications and diagnostics for chronic conditions, as
      well as strengthening the gate keeping function of the primary care services are
      important measures to enhance financial protection for urban poor. Our findings
      call for inclusion of outpatient care for chronic conditions in existing
      government-initiated health insurance schemes.

PMID- 23158476
TI  - The authors reply: following the patient's best interest--uncontrolled donation
      after circulatory determination of death.

PMID- 23158477
TI  - Defibrillator charging before rhythm analysis significantly reduces hands-off
      time during resuscitation: a simulation study.
AB  - BACKGROUND: Our objective was to reduce hands-off time during cardiopulmonary
      resuscitation as increased hands-off time leads to higher mortality. METHODS: The
      European Resuscitation Council (ERC) 2005 and ERC 2010 guidelines were compared
      with an alternative sequence (ALT). Pulseless ventricular tachycardia and
      asystole were presented randomly to all participants in a simulation setting. A
      manikin (Resusci Anne; Laerdal Scandinavia A/S, Stavanger, Norway) and a
      defibrillator (LIFEPACK 12; Physio-Control, Inc, Redmond, WA, USA) were used. In
      ALT, chest compressions were only interrupted for postcharging rhythm analysis
      and immediate shock delivery. Comparing ALT to ERC 2005 and ERC 2010 shock
      delivery was done using paddles and pads, respectively. RESULTS: Sample sizes
      were calculated with alpha of .05 and 90% power. Hence, we needed 4 and 12
      participants, respectively. In ERC 2005 vs ALT, 10 physicians were included. All
      had prior experience in advanced life support. Chest compressions were shorter
      interrupted using ALT (mean, 6.7 vs 13.0 seconds). Analyzing data for ventricular
      tachycardia scenarios only, hands-off time was shorter using ALT (mean, 7.1 vs
      18.2 seconds). In ERC 2010 vs ALT, 12 physicians were included. Two physicians
      had not prior experience in advanced life support. Hands-off time was reduced
      using ALT (mean, 3.9 vs 5.6 seconds). Looking solely at ventricular tachycardia
      scenarios, hands-off time was shortened using ALT (mean, 4.5 vs 7.6 seconds). No
      significant reduction was observed in either of the asystole scenarios.
      CONCLUSION: In a simulation setting, we demonstrated that charging of the
      defibrillator before rhythm analysis significantly reduced hands-off time
      compared with the ERC 2005 and ERC 2010 guidelines.

PMID- 23158479
TI  - [How to recognize and manage functional gastrointestinal disorders with
      concomitant psychological disorder].

PMID- 23158478
TI  - Cell line derived multi-gene predictor of pathologic response to neoadjuvant
      chemotherapy in breast cancer: a validation study on US Oncology 02-103 clinical
      trial.
AB  - BACKGROUND: The purpose of this study is to assess the predictive accuracy of a
      multi-gene predictor of response to docetaxel, 5-fluorouracil, epirubicin and
      cyclophosphamide combination chemotherapy on gene expression data from patients
      who received these drugs as neoadjuvant treatment. METHODS: Tumor samples were
      obtained from patients with stage II-III breast cancer before starting
      neoadjuvant chemotherapy with four cycles of 5
      fluorouracil/epirubicin/cyclophosphamide (FEC) followed by four cycles of
      docetaxel/capecitabine (TX) on US Oncology clinical trial 02-103. Most patients
      with HER-2-positive cancer also received trastuzumab (H). The chemotherapy
      predictor (TFEC-MGP) was developed from publicly available gene expression data
      of 42 breast cancer cell-lines with corresponding in vitro chemotherapy
      sensitivity results for the four chemotherapy drugs. No predictor was developed
      for treatment with trastuzumab. The predictive performance of TFEC-MGP in
      distinguishing cases with pathologic complete response from those with residual
      disease was evaluated for the FEC/TX and FEC/TX plus H group separately. The area
      under the receiver-operating characteristic curve (AU-ROC) was used as the metric
      of predictive performance. Genomic predictions were performed blinded to clinical
      outcome. RESULTS: The AU-ROC was 0.70 (95% CI: 0.57-0.82) for the FEC/TX group
      (n=66) and 0.43 (95% CI: 0.20-0.66) for the FEC/TX plus H group (n=25). Among the
      patients treated with FEC/TX, the AU-ROC was 0.69 (95% CI: 0.52-0.86) for
      estrogen receptor (ER)-negative (n=28) and it was 0.59 (95% CI: 0.36-0.82) for ER
      positive cancers (n=37). ER status was not reported for one patient. CONCLUSIONS:
      Our results indicate that the cell line derived 291-probeset genomic predictor of
      response to FEC/TX combination chemotherapy shows good performance in a blinded
      validation study, particularly in ER-negative patients.

PMID- 23158480
TI  - [Pay more attention to the similarities and differences of nocturnal hypoxia of
      chronic obstructive pulmonary disease and overlap syndrome].

PMID- 23158481
TI  - [Multi-centered stratified clinical studies for psychological and sleeping status
      in patients with chronic constipation in China].
AB  - OBJECTIVE: To survey the emotional and sleeping status of patients with chronic
      constipation (CC) and analyze the relationship between psychological status and
      constipated symptoms. METHODS: From January 2009 to April 2010, 5 centers and 25
      stratified hospitals were selected as the representatives of different regions of
      mainland China. The CC questionnaires including constipated symptoms, emotional
      and sleeping status, previous treatments and self-reported impact of constipation
      on health status, etc. Questionnaires were completed by well-trained physicians
      or investigators during face-to-face interviews. CC was diagnosed in accordance
      with the Rome III criteria. RESULTS: A total of 909 valid questionnaires
      analyzed. There were 258 males and 651 females with a mean age of (49 +/- 19)
      years. 41.5% (377 cases) reported "tense feelings" and 38.3% (348 cases) "felt
      downcast" over the past 3 months. The patients feeling tense and(or) downcast
      "frequently" and "most of time" were around 11.3% (103 cases) and 9.4% (85
      cases). And 43.8% (398 cases) patients reported sleeping disorders over the past
      3 months. Regional differences existed in the comorbidities of psychological and
      sleeping disorders in CC patients, especially in those from tertiary hospitals.
      And it was the highest in Beijing area for tense feelings and downcast. The
      sleeping disorders were the most common in the patients from secondary hospitals,
      of which 66.1% (37/56) and 65.0% (39/60) were from Wuhan and Xi'an respectively.
      They were higher than Beijing and Guangzhou (39.7% (23/58), 29.0% (9/31), all P =
      0.001). The patients from rural primary clinics suffered more sleeping disorders
      than those from urban primary cares (P = 0.026). About 35.0% (318 cases) and
      28.4% (258 cases) patients reported their constipation was related with emotional
      and sleeping disorders. The comorbidities of psychological and sleeping disorders
      were more common in severe constipated patients than mild and moderate
      counterparts and resulted in more hospital visits (both P = 0.000). CONCLUSIONS:
      The CC patients often have the comorbidities of psychological and sleeping
      disorders with regional differences. The patients from the hospitals at various
      levels may present different spectrums of comorbidities of psychological and
      sleeping disorders. And the severity of CC influences the moods, sleeps and
      hospital visits.

PMID- 23158482
TI  - [Relationship between intestinal mucosal inflammation and mental disorders in
      patients with irritable bowel syndrome].
AB  - OBJECTIVE: To examine the relationship between inflammation and the comorbidity
      of mental disorders with irritable bowel syndrome (IBS) by comparing intestinal
      mucosa inflammatory biomarkers in patients with and without mental disorders.
      METHODS: A total of 43 consecutive IBS patients fulfilling the Rome III criteria
      and 15 volunteers serving as controls without digestive symptoms were recruited
      and interviewed with Composite International Diagnostic Interview (CIDI) by the
      well-trained staff and thus classified as with or without mental disorders. All
      subjects underwent colonoscopy and biopsies were acquired from the mucosa of
      distal ileum and colon. CD3(+) lymphocytes, mast cells, 5-HT positive cells and
      (indoleamine 2,3-dioxygenase) IDO positive cells were identified
      immunohistologically in mucosa biopsies in volunteers (n = 13), IBS patients
      without mental disorder (n = 24) and IBS patients with mental disorder (n = 19).
      RESULTS: The incidence of mental disorders in IBS patients was significantly
      higher than that in the volunteers (19/43 vs 2/15, P = 0.012), including 9
      patients with anxiety disorders and 8 with mood disorders. (1) The number of mast
      cells in IBS patients with mental disorder and that in IBS patients without
      mental disorder has no statistical significance ((16.7 +/- 3.6)/HP vs (15.4 +/-
      3.1)/HP in distal ileum, (12.8 +/- 2.2)/HP vs (12.3 +/- 2.5)/HP in sigmoid, both
      P > 0.05). Similar results were seen in 5-HT positive cells ((3.7 +/- 0.9)/HP vs
      (3.4 +/- 0.8)/HP in distal ileum, (6.1 +/- 1.8)/HP vs (5.2 +/- 1.8)/HP in
      sigmoid, both P > 0.05). In distal ileum, the number of CD3(+) cells in IBS
      patients with mental disorder has no statistical significance with that in the
      IBS patients without mental disorder ((62 +/- 16)/HP vs (55 +/- 22)/HP, P >
      0.05). Similar results were seen in IDO positive cells (6(2, 8)/HP vs 2(1, 5)/HP,
      P > 0.05). (2) The number of IDO positive cells from distal ileum in IBS patients
      with anxiety disorder was significantly higher than that in the IBS patients
      without mental disorder (6 (4,8) vs 2 (1,5), P = 0.018). The number of mast cells
      from distal ileum in the IBS patients with mood disorder were significantly
      higher than that in those without mental disorders ((18.3 +/- 3.2)/HP vs (15.4 +/
      3.1)/HP, P = 0.032). CONCLUSIONS: Mental disorders in the IBS patients may be
      associated with intestinal mucosal inflammation. The activation of IDO may cause
      the comorbidity of IBS with anxiety disorder while the activation of mast cells
      probably leads to the comorbidity of IBS with mood disorder.

PMID- 23158483
TI  - [Symptomatic features and psychosocial factors in patients with belching
      disorders].
AB  - OBJECTIVE: To explore the symptomatic features and psychosocial factors in
      patients with belching disorders. METHODS: At Peking Union Medical College
      Hospital Outpatient Clinic from September 2010 to January 2011, 21 consecutive
      patients with repetitive belching were profiled by symptom questionnaires,
      including general demographics, spectrum of symptoms, disease course,
      predisposing factors, previous treatment, psychosocial factors, mental status and
      personality traits, etc. Pearson's correlation analysis and exact probability
      were used. RESULTS: Among them, 20 patients fulfilled the Rome III criteria of
      belching disorders. There were 5 males and 15 females with an age range of (49 +/
      10) years. Among them, the belching patterns were daily (n = 18), meal-related
      (n = 16), spontaneous (n = 15), controllable (n = 16) and symptomatic overlapping
      (n = 17). The most common symptoms were functional dyspepsia (FD) (n = 13) and
      gastroesophageal reflux disease (GERD) (n = 11). Sixteen patients experienced
      mental stimulation/negative events and 13 patients were related to family
      tension, work stress and overwork. There were 12 patients with anxiety and/or
      depression and 8 with neurotic personality. The number of overlapping symptoms
      was related to anxiety states (r = 0.47, t = 2.14, P < 0.05). But the severity of
      belching was unrelated to with or without depression and anxiety state (P =
      0.096). CONCLUSIONS: There are a variety of clinical manifestations in patients
      with belching disorders. Belching disorders is often related to emotional change
      and environmental stress and accompanied by abnormal mental and personality
      characteristics. Belching may be an abnormal behavior reaction to
      gastrointestinal discomfort symptoms. The psychological and social factors
      probably play an important role in the pathogenesis of belching disorders.

PMID- 23158484
TI  - [Effects of selenium supplementation on antibodies of autoimmune thyroiditis].
AB  - OBJECTIVE: To evaluate the effects of selenium (Se) supplementation on
      concentrations of thyroid peroxidase antibodies (TPOAb) and TPOAb IgG subclasses
      in autoimmune thyroiditis (AIT) patients with different thyroid functional
      status. METHODS: A blind and placebo-controlled prospective study was performed
      for a total of 134 cases with AIT and thyroid peroxidase antibodies above 300
      U/ml. Their mean age was 41 years (range: 15-70). All of them were recruited from
      Department of Endocrinology, First Affiliated Hospital of China Medical
      University from June 2008 to June 2009 and divided into 2 groups according to
      thyroid function: euthyroidism or subclinical hypothyroidism (n = 89) and
      hypothyroidism (n = 45). Then they were randomized into 2 groups: selenium
      treated and placebo-treated. And 49 cases in subclinical autoimmune thyroiditis
      group and 28 cases in hypothyroidism group received 200 ug oral selenium yeast
      daily for 6 months while others placebo. Serum concentrations of TPOAb, TPOAb IgG
      subclasses, thyroid-stimulating hormone (TSH), free thyroxine (FT(4)) and Se were
      measured at baseline and after 3 and 6 months of follow-up. RESULTS: The TPOAb
      levels showed an overall decrease of 4.3% at 3 months and of 12.6% at 6 months
      (both P < 0.05) post-supplementation in subclinical autoimmune thyroiditis
      patients. In overt hypothyroidism patients, the overall decrease of TPOAb
      concentrations was 21.9% at 3 months and 20.4% at 6 months (both P < 0.05)
      compared with those at pre-treatment. The predominant TPOAb IgG subclasses in
      sera from the AIT patients were IgG1, IgG3 and IgG4 and the positive percentages
      72%, 41% and 72% respectively. The positive rate and concentrations of IgG3 in
      the patients with hypothyroidism were significantly higher than those of
      subclinical autoimmune thyroiditis (P < 0.05). Significant decreases in IgG1 and
      IgG3 levels were noted in subclinical autoimmune thyroiditis group at 6 months
      post-supplementation (P < 0.05). IgG1 levels in overt hypothyroidism decreased
      significantly compared with those at pre-supplementation (P < 0.05). In all
      patients with supplementation (n = 77), the TPOAb levels decreased in 52 at 6
      months while increase or no change occurred in 25. The positive percentage and
      concentrations of IgG1 in patients whose TPOAb levels decreased at 6 months post
      supplementation were markedly higher than those whose TPOAb levels increased (P <
      0.05). CONCLUSION: Se is effective in reducing TPOAb concentrations and the
      predominant decreasing TPOAb IgG subclasses are IgG1 and IgG3. And a high level
      of IgG1 subclass may explain the difficult decline of TPOAb.

PMID- 23158485
TI  - [Clinical experiences on correction of congenital heart diseases with robotic
      technology: a report of 160 cases].
AB  - OBJECTIVE: To summarize the clinical experiences on correction of congenital
      heart disease with robotic technology at a single center. METHODS: Between
      January 2007 and May 2012, this retrospective study recruited 160 consecutive
      patients undergoing robotic surgery for congenital heart diseases. There were 74
      males and 86 females with a median age of 35 years (range: 11-62). The procedures
      included secundum-type atrial septal defect repair (n = 130), ostium primum
      defect repair (n = 1), perimembranous ventricular septal defect repair (n = 21),
      mitral valve repair for anterior leaflet cleft (n = 7) and mitral valve repair
      plus left atrial myxoma resection (n = 1). Cardiopulmonary bypass graft was
      established through cannulation of right femoral artery, vein and right internal
      jugular vein under the guidance of transesophageal ultrasound. Myocardial
      protection was performed with cold blood cardioplegic solution or HTK solution
      and a transthoracic Chitwood clamp was used to occlude ascending aorta. Via three
      8-mm ports and one 15-mm port in right chest, the microscopic instruments were
      manipulated to complete defect closure or mitral valve plasty, utilizing da Vinci
      S or da Vinci SI robotic system. Echocardiography was performed intraoperatively
      and at pre-discharge. Routine follow-ups were conducted. The clinical data of
      operating time, cardiopulmonary bypass time and follow-up examinations were
      retrospectively analyzed. RESULTS: All cases were treated successfully without a
      conversion into median sternotomy. No operative mortality or severe surgical
      complications were observed. Seventy-six cases of secundum-type atrial septal
      defect were completed on beating heart. The learning curves were noted for
      operating time of beating heart group and cross clamp time of arrest heart group.
      No residual shunt, malignant arrhythmia or mitral valve regurgitation was
      detected on intraoperative or postoperative echocardiography and during a median
      follow-up period of (29.1 +/- 16.3) months. CONCLUSION: Robotic minimal access is
      technically feasible and it may be applied in selective patients with atrial
      septal defect, perimembranous ventricular septal defect and mitral valve cleft.

PMID- 23158486
TI  - [MicroRNA profiling in T cells of peripheral blood mononuclear cell from patients
      with primary biliary cirrhosis].
AB  - OBJECTIVE: To explore the expression pattern of microRNA (miRNA) in T cells of
      peripheral blood mononuclear cell (PBMC) from patients with primary biliary
      cirrhosis (PBC). METHODS: The expression profile of miRNA in T cells of PBMC was
      determined by microarray assay and validated by real-time quantitative reverse
      transcription-polymerase chain reaction (qRT-PCR). RESULTS: In comparison with
      the healthy controls, 23 miRNA were down-regulated and 2 miRNA had a higher
      expression (all P < 0.05). As revealed by qRT-PCR, the expressions of miR-346,
      miR-17-5p, miR-20a and miR-let-7b decreased obviously while miR-451 and miR-129
      became up-regulated. The results were in agreement with those of microarray.
      CONCLUSIONS: The PBC patients and healthy controls have significantly different
      expression profiles of microRNA in T cells of PBMC. The differential expression
      of microRNA may be involved in the pathogenesis of PBC.

PMID- 23158487
TI  - [Application of detecting bronchoalveolar lavage fluid Aspergillus galactomannan
      antigen in the diagnosis of pulmonary aspergillosis].
AB  - OBJECTIVE: To prospectively evaluate the utility of detecting bronchoalveolar
      lavage fluid (BALF) Aspergillus galactomannan antigen (GM) in the diagnosis of
      pulmonary aspergillosis. METHODS: From August 2008 to April 2012, 121 patients
      suspected of pulmonary aspergillosis were recruited and classified into pulmonary
      aspergillosis group (n = 57) and non-pulmonary disease group (n = 64) according
      to the 2008 diagnostic criteria and classification of European Organization for
      Research and Treatment of Cancer/National Institute of Mycoses Study
      Group(EORTC/MSG). The absorbency (A) and I value of GM in the patients' serum and
      BALF were detected by enzyme-linked immunosorbent assay (ELISA). And their values
      were compared and analyzed. RESULTS: Twenty cases were confirmed by pathological
      examinations and 37 cases by clinical diagnosis in the pulmonary aspergillosis
      group. The mean rank of GM's I value in the serum and BALF samples was 88.21 and
      86.49. And they significantly increased compared with the non-pulmonary
      aspergillosis group (36.77, 38.30) (P < 0.01). At a different serum GM threshold
      I = 0.5, 0.8, 1.0, the sensitivities were 0.842, 0.649 and 0.228; the
      specificities 0.906, 0.938, 0.929; the positive predictive values 0.889, 0.902,
      0.984 and the negative predictive values 0.866, 0.750, 0.589 respectively. And at
      a different BALF GM threshold I = 0.5, 0.8, 1.0, the sensitivities were 0.930,
      0.657, 0.561; the specificities 0.766, 0.922, 0.969; the positive predictive
      values 0.779, 0.884, 0.941 and the negative predictive values 0.925, 0.756, 0.713
      respectively. CONCLUSION: The detection of GM in BALF may be employed for the
      clinical diagnosis of pulmonary aspergillosis.

PMID- 23158488
TI  - [Reproduction after liver transplantation: a report of 13 cases from a single
      Chinese center].
AB  - OBJECTIVE: To explore the recipient's reproduction after liver transplantation
      (LT) and assess the outcomes of their offspring. METHODS: We retrospectively
      analyzed the reproduction status of 13 post-LT patients among 336 post-LT
      recipients during a follow-up period. Physical and intellectual status of their
      offspring were evaluated by developmental index and Denever developmental
      screening test. RESULTS: A total of 16 children were mothered or fathered by 13
      LT patients. Two female patients mothered a boy and a girl. Ten male patients
      fathered 6 male and 8 female children while another male fathered a child at 28
      gestational weeks. Eleven patients fathered the first gestation 21 mon (medium)
      since LT, and fathered 15 pregnancies. Twelve of 14 deliveries had a mean
      gestation age of (38.2 +/- 1.8) weeks, with a mean birth weight of (3.1 +/- 0.5)
      kg. Among 12 newborns, 3 were premature and 2 of a low birth weight. Two female
      patients delivered 2 babies with a gestation age of 37.3 and 40.4 weeks, a birth
      weight of 2.7 and 3.4 kg, and anoxia neonatorum in one case. No deformity was
      found. Thirteen of 16 children had almost normal developmental indices and ten
      had almost normal Denever developmental screening. CONCLUSION: Post-LT patients
      of reproductive age are able to reproduce offspring. The short-term development
      of their offspring is relatively normal.

PMID- 23158489
TI  - [Analysis of clinical characteristics of partial olfactory dysfunction].
AB  - OBJECTIVE: To apply different types and concentrations of T&T olfactometer
      odorants to exam smell function and explore the clinical characteristics of
      partial olfactory dysfunction. METHODS: From March 2007 to May 2008, a total of
      24 patients with olfactory dysfunction were examined by medical and psychiatric
      history enquiry, physical examination, smell testing and medical imaging.
      Olfactory function of each nostril was assessed separately by T&T olfactometer.
      The test contained five kinds of odorants at different concentrations.
      Recognition threshold (RT) scores for all five odorants and for each individual
      odorant were measured in all patients. RESULTS: Among them, total RT scores were
      normal while single odorant testing yielded only significant higher RT scores for
      one or two odorants. For patients who suffered partial olfactory dysfunction,
      51.4% are for pleasant odors, while the rest are for unpleasant odors.
      CONCLUSION: Normal total RT scores and abnormal single RT scores of T&T
      olfactometer are present in partial olfactory dysfunction. As a special clinical
      manifestation of olfactory disorder, it may be easily ignored in smell testing.

PMID- 23158490
TI  - [Application of karyotypic analysis in myelodysplastic syndrome].
AB  - OBJECTIVE: To explore the applications of karyotypic analysis in the diagnosis
      and prognosis of myelodysplastic syndrome (MDS). METHODS: Chromosomal analysis
      was performed with short-term cell cultures and R-banding techniques in 129 MDS
      patients. And the technique of FISH was employed for clinical follow-ups in 28
      MDS patients. Based on the result of abnormal karyotype, the patients were
      divided into three groups: low risk group , intermediate risk and high risk
      group. The leukemia transformation time and survival time between these three
      groups were compare. RESULTS: Among them, 52 patients (40.3%) had numeral
      karyotypic abnormalities of chromosomes and structural alterations. Complex
      abnormal karyotype was the most common and accounted for 30.8% (16 cases). The
      frequencies of 20q(-) and +8 were 19.2% (10 cases) and 15.4% (8
      cases)respectively. Six cases were positive by FISH, however, of whom, were
      negative for conventional cytogenetics. The follow-up data were available in 88
      patients with a median follow up duration of 11(3, 60) months, 27 cases (30.7%)
      progressed to acute leukemia. The rate of leukemia transformation were 27.8%
      (15/54), 23.5% (4/17) and 47.1% (8/17) in the low, intermediate and high risk
      groups respectively. The median durations of leukemic transformation were > 60
      (14, > 60), 48 (35, > 60) and 7 (6, 12) months in the low, intermediate and high
      risk groups and the median survival times were 26(15, > 60), 21(14, 35) and 10(6,
      13) months respectively. The median durations of leukemic transformation and
      median survival periods in the high-risk groups were shorter than those in the
      low and intermediate risk groups (all P < 0.05). CONCLUSION: Karyotypic analysis
      has important values in the diagnosis and prognosis of MDS.

PMID- 23158491
TI  - [Effects of age, gender and urinary diversion category on perioperative
      complications of radical cystectomy].
AB  - OBJECTIVE: To explore the association of age, gender and urinary diversion
      category with postoperative complications of radical cystectomy. METHODS: A total
      of 374 patients with bladder cancer undergoing modified radical cystectomy and
      urinary diversion between March 2000 and June 2011 were retrospectively reviewed.
      Their demographic, perioperative and complication data were recorded. And
      multivariable Logistic regression was used to investigate the predictors of
      perioperative complications. RESULTS: Among them, 38.8% (145/374) received ileal
      conduit, 47.9% (179/374) orthotopic ileal neobladder and 13.4% (50/374)
      orthotopic colonic neobladder. The overall perioperative complication rate was
      37.4% (140/374). And 21.4% (80/374) experienced at least one complication within
      Day 90 postoperation while 16.3% (61/374) had the long-term complications (> Day
      90). There was no significant association between patients age (P = 0.15) and
      perioperative complications or between gender (P = 0.16) and complication.
      Urinary diversion (OR = 0.26, 95%CI: 0.16 - 0.43) was the only variable
      significantly associated with the perioperative urinary complications.
      CONCLUSION: The categories of urinary diversion may be used as a single predictor
      for complications after radical cystectomy.

PMID- 23158492
TI  - [Mechanisms of mucus hypersecretion in airway of rats induced by synergies
      between cold air and cigarette smoke inhalation and intervention effects of
      drugs].
AB  - OBJECTIVE: To explore the mechanisms of mucus hypersecretion in airway of rats
      induced by the synergies between cold air and cigarette smoke inhalation and
      understand the intervention effects of saussurea and budesonide in this process.
      METHODS: A total of 70 SD rats were randomly divided into 7 groups. Group A:
      control; Group B: cold stimulation group receiving cold air inhalation for 3 h
      daily for 40 d; Group C: cigarette smoke inhalation group receiving cigarette
      smoke inhalation for 0.5 h daily for 40 d; Group D: cigarette smoke inhalation +
      cold stimulation group; Group E: cigarette smoke inhalation + cold stimulation +
      saussurea (0.8 mg/kg saussurea intraperitoneally injected once daily for 40 d);
      Group F: cigarette smoke inhalation + cold stimulation + inhaled budesonide (0.5
      mg/kg inhaled once daily for 40 d); Group G: cigarette smoke inhalation + cold
      stimulation + saussurea + inhaled budesonide. The relative quantities of TRPM8
      mRNA within bronchial epithelium of each group were detected by real-time
      polymerase chain reaction (PCR) and TRPM8 protein was detected by
      immunohistochemical assay and Western blot. The levels of mucin (MUC) 5AC,
      interleukin 8 (IL-8) and tumor necrosis factor alpha (TNF-alpha) in
      bronchoalveolar lavage fluid (BALF) were detected by enzyme-linked immunosorbent
      assay. RESULTS: TRPM8 mRNA of groups A-G were 1.00 +/- 0.00, 0.98 +/- 0.07, 2.27
      +/- 0.29, 2.31 +/- 0.30, 1.55 +/- 0.38, 1.66 +/- 0.40 and 1.31 +/- 0.23; TRPM8
      protein 0.16 +/- 0.05, 0.16 +/- 0.04, 0.22 +/- 0.06, 0.25 +/- 0.05, 0.17 +/-
      0.04, 0.18 +/- 0.03, 0.15 +/- 0.05, 0.25 +/- 0.04, 0.24 +/- 0.03, 0.58 +/- 0.06,
      0.56 +/- 0.09, 0.41 +/- 0.09, 0.39 +/- 0.07 and 0.20 +/- 0.06 respectively. TRPM8
      mRNA and protein of groups C and D were significantly higher than those of group
      A. And groups E, F and G were significantly lower than those of group D (all P <
      0.05). In BALF of groups A-G, MUC5AC were (57 +/- 6), (69 +/- 5), (66 +/- 4),
      (185 +/- 43), (142 +/- 30), (147 +/- 36) and (60 +/- 11) ug/mg, IL-8 (58 +/- 14),
      (146 +/- 38), (134 +/- 29), (379 +/- 101), (262 +/- 67), (294 +/- 70) and (81 +/-
      27) ng/L, TNF-alpha(153 +/- 28), (208 +/- 90), (274 +/- 64), (600 +/- 113), (458
      +/- 96), (498 +/- 84) and (169 +/- 65) ng/L respectively. The values of groups B,
      C and D were significantly higher than those of group A (all P < 0.05) while
      groups E, F and G were significantly lower than those of group D (all P < 0.05).
      Cigarette smoke inhalation and cold stimulation synergistically enhanced the
      expression of MUC5AC, IL-8 and TNF-alpha. Saussurea and inhaled budesonide
      synergistically inhibited the expression of MUC5AC, IL-8 and TNF-alpha.
      CONCLUSIONS: Cold air inhalation evokes the release of proinflammatory cytokines
      and MUC5AC via activated TRPM8 channel up-regulated by cigarette smoke
      inhalation. Saussurea and inhaled budesonide synergistically inhibits the above
      mentioned process.

PMID- 23158493
TI  - [Involvement of Wnt/beta-catenin signaling in the osteogenesis of bone marrow
      mesenchymal stem cells induced by drynaria total flavonoids].
AB  - OBJECTIVE: To explore the effects of the expression of Wnt/beta-catenin signaling
      factor mRNA during drynaria total flavonoids on the osteogenic differentiation of
      bone marrow mesenchymal stem cells (BMSCs). METHODS: The BMSCs were isolated from
      SD rats by whole bone marrow culture method and purified by passage. And the P3
      BMSCs were intervened with 100 ug/ml drynaria total flavonoids. At Day 21,
      mineralized staining was performed. At Days 7, 14, 21 and 28 post-intervention,
      the activity of alkaline phosphatase (ALP) was detected and polymerase chain
      reaction (PCR) used to detect the expressions of Wnt/beta-catenin signaling
      pathway related factors beta-catenin, LEF-1 and cycline D mRNA. RESULTS: At each
      time point post-intervention, comparing the ALP activity in cell supernatant
      between two group, the drynaria total flavonoids group was higher than the blank
      control group (7 d: 11.10 +/- 0.08 vs 1.61 +/- 0.14; 14 d: 24.62 +/- 0.34 vs 1.64
      +/- 0.04; 21 d: 18.41 +/- 0.06 vs 1.53 +/- 0.04; 28 d: 14.9 +/- 0.14 vs 1.52 +/-
      0.04; all P < 0.01). At Day 21, upon staining with alizarin red, the drynaria
      total flavonoids group was positive while the blank control group negative. At
      Day 14, the expression of beta-catenin mRNA was higher in the drynaria total
      flavonoids group higher than that in the blank control group (0.357 +/- 0.063 vs
      0.174 +/- 0.013, P < 0.05). At Day 7, the expressions of LEF-1 and cycline D mRNA
      were higher in the drynaria total flavonoids group than those in the blank
      control group (LEF-1 0.0611 +/- 0.0002 vs 0.0345 +/- 0.0131; cycline D 0.1510 +/-
      0.0255 vs 0.0718 +/- 0.0294, all P < 0.05). CONCLUSION: Drynaria total flavonoids
      induce BMSCs to differentiate into osteoblasts. And it is accompanied with the
      altered expression of Wnt/beta-catenin signaling pathway related factor mRNA.

PMID- 23158494
TI  - [Role of heme oxygenase-1 in the apoptosis of mesenchymal stem cells].
AB  - OBJECTIVE: To explore the role of heme oxygenase-1 (HO-1) in the apoptosis of
      mesenchymal stem cells (MSCs). METHODS: The method of reverse transcription PCR
      (RT-PCR) was employed to detect the expression of HO-1 mRNA in bone marrow MSCs.
      Morphologic observations, flow cytometry Annexin-V and DNA analysis were used to
      detect apoptosis and determine the content of DNA of MSCs after a 12-hour
      treatment of Znpp-IX, a Ho-1 special inhibitor. RESULTS: HO-1 mRNA was expressed
      in normal bone marrow MSCs. After culturing Znpp-IX for 12 h, MSCs showed volume
      reduction and membrane shrinkage. The cells of apoptotic Annexin V(+)/PI(-)
      increased significantly (61.21% +/- 5.28% vs 7.48% +/- 0.69%, P < 0.05). The peak
      of apoptosis was distinct on the distribution graph of DNA (21.36% +/- 0.49% vs
      1.02% +/- 0.05%, P < 0.05). CONCLUSION: HO-1 plays an anti-apoptotic role in
      human bone marrow mesenchymal stem cells.

PMID- 23158495
TI  - Ambroxol as a pharmacological chaperone for mutant glucocerebrosidase.
AB  - Gaucher disease (GD) is characterized by accumulation of glucosylceramide in
      lysosomes due to mutations in the GBA1 gene encoding the lysosomal hydrolase beta
      glucocerebrosidase (GCase). The disease has a broad spectrum of phenotypes, which
      were divided into three different Types; Type 1 GD is not associated with primary
      neurological disease while Types 2 and 3 are associated with central nervous
      system disease. GCase molecules are synthesized on endoplasmic reticulum (ER)
      bound polyribosomes, translocated into the ER and following modifications and
      correct folding, shuttle to the lysosomes. Mutant GCase molecules, which fail to
      fold correctly, undergo ER associated degradation (ERAD) in the proteasomes, the
      degree of which is one of the factors that determine GD severity. Several
      pharmacological chaperones have already been shown to assist correct folding of
      mutant GCase molecules in the ER, thus facilitating their trafficking to the
      lysosomes. Ambroxol, a known expectorant, is one such chaperone. Here we show
      that ambroxol increases both the lysosomal fraction and the enzymatic activity of
      several mutant GCase variants in skin fibroblasts derived from Type 1 and Type 2
      GD patients.

PMID- 23158496
TI  - Regulation of podosome formation, microglial migration and invasion by Ca(2+)
      signaling molecules expressed in podosomes.
AB  - BACKGROUND: Microglia migrate during brain development and after CNS injury, but
      it is not known how they degrade the extracellular matrix (ECM) to accomplish
      this. Podosomes are tiny structures with the unique ability to adhere to and
      dissolve ECM. Podosomes have a two-part architecture: a core that is rich in F
      actin and actin-regulatory molecules (for example, Arp2/3), surrounded by a ring
      with adhesion and structural proteins (for example, talin, vinculin). We recently
      discovered that the lamellum at the leading edge of migrating microglia contains
      a large F-actin-rich superstructure ('podonut') composed of many podosomes.
      Microglia that expressed podosomes could degrade ECM molecules. Finely tuned
      Ca(2+) signaling is important for cell migration, cell-substrate adhesion and
      contraction of the actomyosin network. Here, we hypothesized that podosomes
      contain Ca(2+)-signaling machinery, and that podosome expression and function
      depend on Ca(2+) influx and specific ion channels. METHODS: High-resolution
      immunocytochemistry was used on rat microglia to identify podosomes and novel
      molecular components. A pharmacological toolbox was applied to functional assays.
      We analyzed roles of Ca(2+)-entry pathways and ion channels in podosome
      expression, microglial migration into a scratch-wound, transmigration through
      pores in a filter, and invasion through MatrigelTM-coated filters. RESULTS:
      Microglial podosomes were identified using well-known components of the core (F
      actin, Arp2) and ring (talin, vinculin). We discovered four novel podosome
      components related to Ca(2+) signaling. The core contained calcium release
      activated calcium (CRAC; Orai1) channels, calmodulin, small-conductance Ca(2+)
      activated SK3 channels, and ionized Ca(2+) binding adapter molecule 1 (Iba1),
      which is used to identify microglia in the CNS. The Orai1 accessory molecule,
      STIM1, was also present in and around podosomes. Podosome formation was inhibited
      by removing external Ca(2+) or blocking CRAC channels. Blockers of CRAC channels
      inhibited migration and invasion, and SK3 inhibition reduced invasion.
      CONCLUSIONS: Microglia podosome formation, migration and/or invasion require
      Ca(2+) influx, CRAC, and SK3 channels. Both channels were present in microglial
      podosomes along with the Ca(2+)-regulated molecules, calmodulin, Iba1 and STIM1.
      These results suggest that the podosome is a hub for sub-cellular Ca(2+)
      signaling to regulate ECM degradation and cell migration. The findings have broad
      implications for understanding migration mechanisms of cells that adhere to, and
      dissolve ECM.

PMID- 23158497
TI  - Physiological response of the sea urchin Paracentrotus lividus fed with the
      seagrass Posidonia oceanica and the alien algae Caulerpa racemosa and Lophocladia
      lallemandii.
AB  - The aim was to determine the effects of alien algae feeding on biomarkers of
      oxidative stress in the sea urchin Paracentrotus lividus. Sea urchins were fed
      during three months with the native seagrass Posidonia oceanica, and the alien
      macroalgae Caulerpa racemosa and Lophocladia lallemandii and biochemical analysis
      were performed in the gonads. A control group was immediately processed after
      sampling from the sea. Antioxidant enzyme and glutathione S-transferase
      activities and GSH concentration were significantly higher in sea urchins fed
      with alien algae when compared with the control group and the one fed with P.
      oceanica group. This response was more intense in the group fed with L.
      lallemandii respect to the C. racemosa group. The concentration of MDA, protein
      carbonyl derivates and 8-OHdG reported no significant differences between
      treatments. In conclusion, the invasive algae C. racemosa and L. lallemandii
      induced an antioxidant response in P. lividus without evident oxidative damage.

PMID- 23158498
TI  - Investigation of disease outbreaks with genome sequencing.

PMID- 23158499
TI  - Whole-genome sequencing to delineate Mycobacterium tuberculosis outbreaks: a
      retrospective observational study.
AB  - BACKGROUND: Tuberculosis incidence in the UK has risen in the past decade.
      Disease control depends on epidemiological data, which can be difficult to
      obtain. Whole-genome sequencing can detect microevolution within Mycobacterium
      tuberculosis strains. We aimed to estimate the genetic diversity of related M
      tuberculosis strains in the UK Midlands and to investigate how this measurement
      might be used to investigate community outbreaks. METHODS: In a retrospective
      observational study, we used Illumina technology to sequence M tuberculosis
      genomes from an archive of frozen cultures. We characterised isolates into four
      groups: cross-sectional, longitudinal, household, and community. We measured
      pairwise nucleotide differences within hosts and between hosts in household
      outbreaks and estimated the rate of change in DNA sequences. We used the findings
      to interpret network diagrams constructed from 11 community clusters derived from
      mycobacterial interspersed repetitive-unit-variable-number tandem-repeat data.
      FINDINGS: We sequenced 390 separate isolates from 254 patients, including
      representatives from all five major lineages of M tuberculosis. The estimated
      rate of change in DNA sequences was 0.5 single nucleotide polymorphisms (SNPs)
      per genome per year (95% CI 0.3-0.7) in longitudinal isolates from 30 individuals
      and 25 families. Divergence is rarely higher than five SNPs in 3 years. 109 (96%)
      of 114 paired isolates from individuals and households differed by five or fewer
      SNPs. More than five SNPs separated isolates from none of 69 epidemiologically
      linked patients, two (15%) of 13 possibly linked patients, and 13 (17%) of 75
      epidemiologically unlinked patients (three-way comparison exact p<0.0001).
      Genetic trees and clinical and epidemiological data suggest that super-spreaders
      were present in two community clusters. INTERPRETATION: Whole-genome sequencing
      can delineate outbreaks of tuberculosis and allows inference about direction of
      transmission between cases. The technique could identify super-spreaders and
      predict the existence of undiagnosed cases, potentially leading to early
      treatment of infectious patients and their contacts. FUNDING: Medical Research
      Council, Wellcome Trust, National Institute for Health Research, and the Health
      Protection Agency.

PMID- 23158500
TI  - Risk factors of non-alcoholic fatty liver disease in patients with inflammatory
      bowel disease.
AB  - BACKGROUND: Metabolic risk factors are associated with non-alcoholic fatty liver
      disease (NAFLD), but they are less frequent in inflammatory bowel disease (IBD).
      AIM: This study evaluates the frequency of NAFLD and its risk factors among IBD
      patients including anti-TNF-alpha therapy. METHODS: IBD patients who underwent
      abdominal imaging from January, 2009 to December, 2010 were analyzed in this
      nested, case-controlled study. IBD patients with NAFLD by imaging were compared
      with those who had no evidence of NAFLD (control). RESULTS: Among 928 IBD
      patients, 76 (8.2%) had evidence of NAFLD by imaging, and were compared to 141
      patients without NAFLD evaluated (study: control ratio=~1:2). NAFLD patients were
      older (46.0 +/- 13.3 vs. 42.0 +/-14.1 years; p=0.018) and had a later onset of
      IBD compared to the control group (37.2 +/- 15.3 vs. 28.7 +/- 23.8 years;
      p=0.002). Metabolic syndrome was present in 29.0% of NAFLD patients, with a
      median Adult Treatment Panel risk factor of 2 [Interquartile range 1,3]. Patients
      not receiving anti-TNF-alpha therapy had a higher occurrence of NAFLD (p=0.048).
      In multivariate analysis, hypertension (OR=3.5), obesity (OR=2.1), small bowel
      surgeries (OR=3.7), and use of steroids at the time of imaging (OR=3.7) were
      independent factors associated with NAFLD. CONCLUSION: NAFLD occurred in 8.2% of
      the IBD population. NAFLD patients were older and had a later onset of IBD
      disease. IBD patients develop NAFLD with fewer metabolic risk factors than non
      IBD NAFLD patients. It is also less common among patients who received anti-TNF
      alpha therapy.

PMID- 23158501
TI  - Recovery of nitrogen fixation after short-term flooding of the nodulated root
      system of soybean.
AB  - Nitrogen fixation of terrestrial legumes is strongly and rapidly diminished under
      flooding. Although recovery is possible with the formation of aerenchyma,
      information is scarce regarding recovery after draining following short-term
      flooding, before the appearance of morphological adaptations. This study used
      soybean (Glycine max) plants nodulated with Bradyrhizobium elkanii to determine
      xylem sap glutamine as an indication of nitrogen fixation activity during
      recovery from different periods of flooding. Xylem glutamine levels showed rapid
      recovery (within 90 min) following periods of flooding up to 4 h. Recovery was
      progressively slower after longer periods of flooding. After 48 h flooding very
      little recovery could be observed within the first 120 min after draining but
      recovery was possible within 48 h. Consistent with the changes in xylem
      glutamine, direct measurements of apparent nitrogenase activity carried out
      immediately on draining revealed rapid recovery after flooding for 1 h and slow
      recovery following 48 h of flooding. In the latter case, nitrogenase activity
      largely recovered 24 h after draining. Experiments with (15)N(2) incorporation
      into amino acids exported in the xylem sap revealed that glutamine was by far the
      most highly labelled amino acid in sap collected over the first 30 min of
      exposure to the isotope. This is conclusive evidence that xylem sap glutamine is
      an immediate product of N(2) fixation and export. The changes in xylem sap
      glutamine seen on flooding (decline) and after draining (recovery) can therefore
      be attributed to changes in nitrogenase activity. The data show that xylem sap
      glutamine is a useful means for assessing changes in nitrogenase activity,
      especially when the root system is submersed in water and activity cannot be
      measured directly.

PMID- 23158502
TI  - A novel Delta(1)-pyrroline-5-carboxylate synthetase gene of Medicago truncatula
      plays a predominant role in stress-induced proline accumulation during symbiotic
      nitrogen fixation.
AB  - Proline accumulates in environmentally stressed plant cells including those of
      legume roots and nodules, but how its level is regulated is poorly understood.
      Delta(1)-Pyrroline-5-carboxylate synthetase (P5CS), the committed-step enzyme of
      proline biosynthesis, is encoded by two duplicated genes in many plants. Here, we
      isolated MtP5CS3, a third gene, from Medicago truncatula, whose predicted
      polypeptide sequence is highly similar to those of previously isolated MtP5CS1
      and MtP5CS2 except an extra amino-terminal segment. MtP5CS3 was strongly
      expressed under salinity and drought in shoots and nodulating roots, while
      MtP5CS1 was constitutive and MtP5CS2 induced by abscisic acid. Under salinity,
      MtP5CS3 promoter was more active than those of MtP5CS1 and MtP5CS2, as shown by
      GUS fusions. Translationally fused MtP5CS1-GFP was localized in the cytoplasm,
      whereas significant proportions of MtP5CS2-GFP and MtP5CS3-GFP were co-localized
      with rubisco small subunit protein-fused RFP in transformed hairy root cells.
      Under salinity, RNA silencing of MtP5CS1 or MtP5CS2 strongly induced MtP5CS3
      expression, while that of MtP5CS3 decreased free proline content and nodule
      number. Consistently, Mtp5cs3, a loss-of-function mutant, accumulated much less
      proline, formed fewer nodules, and fixed nitrogen significantly less efficiently
      than the wild type under salinity. Thus, MtP5CS3 plays a critical role in
      regulating stress-induced proline accumulation during symbiotic nitrogen
      fixation.

PMID- 23158503
TI  - Metatarsocuneiform joint resection arthroplasty for atraumatic osteoarthrosis: an
      alternative to arthrodesis.
AB  - The reported operative treatment of primary osteoarthrosis of the
      metatarsocuneiform joint has focused primarily on methods of arthrodesis.
      Arthrodesis of the metatarsocuneiform joint can result in complications in the
      older or obese patient who is unable to tolerate non-weightbearing. Age and
      health status can also increase the rate of nonunion and venous thromboembolism,
      especially in the immobile patient. We present a technique not previously
      described. The procedure is presented as an alternative to arthrodesis and
      involves resection arthroplasty of the metatarsocuneiform joint.

PMID- 23158504
TI  - Osteitis of the fourth metatarsal caused by a date palm thorn in a child: why the
      dorsum of the foot is the most commonly injured site.
AB  - The palms are frequent in the region of eastern Morocco. An insidious onset of a
      lytic lesion in the base of the fourth metatarsal caused by a date palm thorn in
      a 20-year-old patient is presented. An untreated embedded thorn can cause late
      complications, including periostitis or osteomyelitis. In most cases, removal of
      the foreign body is easy, and no surgical care is needed. If detected, these
      injuries can be treated without complications. In children, however, the
      diagnosis can be very easily missed, especially if the child has aphasia and
      deafness, which was present in our patient. These can influence communication
      between the child and family, such that the patient is unable to inform the
      family about what object pricked him (e.g., date palm thorn, toothpick, insect)
      and is unable to tell the family that the foreign object remains embedded. This
      major communication issue between the child and family can result in potentially
      avoidable complications such as osteitis. No other issues were present in our
      patient that could have caused a delay in diagnosis, such as fear of punishment
      or fear of medical treatment. We present a case of date palm thorn-induced
      periostitis of the base of the fourth metatarsal. Surgical exploration revealed a
      2.5-cm palm tree thorn embedded in granulation tissue, forming an abscess. The
      lesion was successfully treated by curettage of the lesion and removal of the
      thorn embedded in the periosteum of the metatarsal base. The purpose of the
      present report was to explain the mechanism of this rare entity and the frequency
      of this lesion on the dorsal aspect of the foot rather than on the plantar.
      Despite the absence of a definite history of trauma, organic foreign material
      should be in the differential diagnosis of a lytic lesion of the bone, especially
      in patients who have a problem with deafness or aphasia.

PMID- 23158505
TI  - Medication and breastfeeding.
AB  - It is well accepted that the best feeding method for infants is breastfeeding,
      due to its numerous biological and clinical effects on child and maternal health.
      The use of medication by the nursing mother and the physician's advice to stop
      nursing are the most common reasons for the cessation of breastfeeding. The
      physician plays an extremely delicate role and should be able to assess risks and
      benefits for both mother and child. The main factors that must be taken into
      account include pharmacokinetics, the duration of maternal therapy, the age of
      the infant and the general health of the infant. All physicians should have
      access to reliable and updated information on medication safety during
      breastfeeding (reference books, online medical literature). Few drugs have been
      demonstrated to be absolutely contraindicated during breastfeeding. Nevertheless
      clear, safe and reliable information is still lacking for most drugs and it would
      be desirable to improve the knowledge about mechanisms and consequences of infant
      exposure to drug present in milk.

PMID- 23158506
TI  - Critical appraisal of different anthropometric charts to evaluate postnatal
      growth of preterm infants.
AB  - Preterm infants' survival has greatly increased in the last few decades thanks to
      the improvement in obstetrical and neonatal care. The correct evaluation of
      postnatal growth of these babies is nowadays of primary concern, although the
      definition of their optimal postnatal growth pattern is still controversial.
      Concerns have also been raised about the strategies to monitor their growth,
      specifically in relation to the charts used. At present, the charts available in
      clinical practice are fetal growth charts, neonatal anthropometric charts and
      postnatal growth charts for term infants. None of these, for different reasons,
      is suitable to correctly evaluate preterm infant growth. Recently, an
      international project has recently started aiming to create prescriptive standard
      for the evaluation of postnatal growth of preterm infants (INTERGROWTH-21st).
      Alternatively, at present, while specific charts for evaluating preterm infant
      postnatal growth are lacking, the best compromise is likely to be as follows:
      from birth to term neonatal anthropometric charts; International longitudinal
      charts WHO 2006 or CDC 2002 from term to childhood.

PMID- 23158507
TI  - Biological, nutritional and clinical aspects of feeding preterm infants with
      human milk.
AB  - Benefits of breastfeeding are widely recognized, during the last decades human
      milk has been identified as the normative standard for infant feeding and
      nutrition. Recent evidence focused on specific bioactive and immunomodulatory
      factors, such as oligosaccharides, lactose, glycosaminoglycans of human milk and
      the variability of their concentrations during lactation in both term and preterm
      milk. Human milk should be fortified with proteins, minerals and vitamins to
      ensure optimal nutrient intake for preterm VLBWI infants. Best fortification
      strategies as well as the optimal composition of fortifiers are still object of
      research. Short and long-term clinical, metabolic, immunologic and
      neurodevelopmental advantages of breastfeeding ndividualizes fortification -
      particulary adjustable fortification- has proven to be effective when compared to
      formula are well documented. Moreover several non-experimental studies observed
      that clinical feeding tolerance is improved and the attainment of full enteral
      feeding is quicker by a diet of human milk. In addition, benefits of
      breastfeeding on psychological and relational aspects have to be considered.
      Mother?s own milk remains the first choice for all neonates, when it is not
      available or not sufficient despite significant lactation support, donor milk
      represents the second best alternative and although some nutritional elements are
      inactivated by the pasteurization process, it still has documented advantages
      compared to formula.

PMID- 23158508
TI  - Auxological evaluation of newborns.
AB  - Auxological evaluation of the newborn should be based on accurate anthropometry
      at birth and a reliable estimate of gestational age (GA). However, a
      comprehensive evaluation of the neonate should consider not only anthropometric
      traits at birth, but also fetal ultrasound biometry and Doppler velocimetry. Many
      charts have been proposed, but they are hardly comparable with each other, due to
      numerous methodological problems. The Italian Societies of Neonatology, of
      Pediatric Endocrinology and Diabetology and the Italian Society of Medical
      Statistics and Clinical Epidemiology promoted a multicenter survey with the aim
      to produce an Italian neonatal anthropometric reference (Italian Neonatal Study
      [INeS] charts) fulfilling the set of the criteria that a reliable neonatal chart
      should possess. In order to construct an international standard, an international
      project (INTERGROWTH-21st) has started a study aiming to create a prescriptive
      standard. Until an international standard is developed, the use of national
      updated reference charts is recommended.

PMID- 23158509
TI  - Donor human milk versus mother's own milk in preterm VLBWIs: a case control
      study.
AB  - As for term infants, over the past decades there has been increasing evidence of
      the benefits of human milk in the feeding of Very Low Birth Weight Infants
      (VLBWI), influencing not only short-term health outcomes but also long-term
      neurodevelopmental, metabolic outcomes, and growth. Mother's own milk is the
      first choice for all neonates including preterm infants, when it is unavailable
      or in short supply, pasteurized donor breast milk offers a safe alternative and
      is considered the next best choice. The main aim of this case-control
      retrospective analysis was to evaluate short term advantages of mother's own milk
      as a sole diet compared to donor milk as a sole diet, in terms of growth,
      antiinfectious properties, feeding tolerance, NEC and ROP prevention in a
      population of VLBWI born in a tertiary center. We did not find significant
      differences in clinical outcome from mother's own milk compared with pasteurized
      donor milk. Only a slight and statistically not significant difference in growth
      could be observed, in favour of maternal milk. We conclude that the maximum
      effort should always be put in supporting and promoting breastfeeding and donor
      milk used not only as an alternative to mother's milk but also as a breastfeeding
      promotion and support strategy.

PMID- 23158510
TI  - Hyperbilirubinemia and management of breastfeeding.
AB  - Hyperbilirubinemia and jaundice are natural, physiological phenomena which are
      only to be expected in the neonatal period, within certain limits. The highest
      percentage of jaundice in breastfed newborns should be evaluated in connection
      with inadequate management of breastfeeding rather than a direct effect of breast
      milk. Breastfeeding is also linked to visible jaundice persisting beyond the
      first two weeks of life (?breast milk jaundice?), but the appearance of skin
      jaundice is not a reason for interrupting breastfeeding which can and should
      continue without any interruption in most cases. There have been numerous
      contributions to the literature which have rescaled the direct role of breast
      milk both in early jaundice and in the more severe cases of late jaundice. The
      reviewed guidelines for detection and management of hyperbilirubinemia underline
      how prevention of badly managed breastfeeding and early support for the couple
      mother-child are effective prevention measures against severe early-onset
      jaundice; furthermore, the breastfeeding interruption is no longer recommended as
      a diagnostic procedure to identify breast milk jaundice because of its low
      specificity and the risk to disregarding the detection of a potentially dangerous
      disease.

PMID- 23158511
TI  - Communication in NICUs.
AB  - In a Neonatal Intensive Care Unit (NICU) counseling should be a shared culture
      for all the care givers: it should be developed by all the professionals, to face
      up to parents' needs of information, explanations, facility of decisions, finding
      of resources, agreement, help, reassurance, attention. The first essential aspect
      is the training in counseling skills, by periodic courses for all professionals
      of the department (physicians, nurses, and physiotherapists). In our department,
      a professional counselor is present, assisting the medical staff in direct
      counseling. The counselor's intervention allows a better parent orientation in
      the situation. A more effective sharing of these rules also facilitates the
      communication among parents and medical staff. Periodic meetings are established
      among the medical staff, in which the professional counselor discusses difficult
      situations to share possible communicative strategies. We wanted to have not only
      a common communicative style, but also common subjects, independent from the
      characteristics of each of us. Individuals are often faced with different
      situations. For every setting that we more frequently face in communication (for
      example the first interview with a parent of a very preterm infant) we have built
      an 'algorithm' that follows a pattern: (1) information always given; (2) frequent
      questions from parents; and (3) frequent difficulties in the communication.
      Counselling is also a tool to face some critical issue, such as the decision to
      open the department to parents 24 h on 24, or the promotion of mother's milk use
      in Very Low Birth Weight Infants (VLBWI).

PMID- 23158512
TI  - Metabolism and biological functions of human milk oligosaccharides.
AB  - It is well known that breastfeeding is beneficial both for its nutritional
      properties and for the presence of biologically active compounds. Among these,
      human milk oligosaccharides (HMOs), representing the third largest fraction of
      human milk, have been assigned important biological functions, such as prebiotic
      and immunomodulatory and antimicrobial effects. HMOs are synthesized in the
      mammary gland by glycosyltransferase enzymes and can be divided in core
      oligosaccharides, sialo-oligosaccharides, fucosyl-oligosaccharides and sialo
      fucosyl-oligosaccharides on the basis of their chemical structure.
      Glycosyltransferases enzymes are partially regulated by genetic mechanisms;
      according to the expression of secretory and Lewis' genes, it is possible to
      classify human milk in 4 different secretory groups. We hereby present a review
      of the current knowledge concerning HMOs, their metabolism and main biological
      functions.

PMID- 23158513
TI  - Cow's milk proteins in human milk.
AB  - Cow's milk proteins (CMPs) are among the best characterized food allergens. Cow's
      milk contains more than twenty five different proteins, but only whey proteins
      alpha-lactalbumin, beta-lactoglobulin, bovine serum albumin (BSA), and
      lactoferrin, as well as the four caseins, have been identified as allergens. Aim
      of this study was to investigate by proteomics techniques cow's milk allergens in
      human colostrum of term and preterm newborns' mothers, not previously detected,
      in order to understand if such allergens could be cause of sensitization during
      lactation. Term colostrum samples from 62 healthy mothers and preterm colostrum
      samples from 11 healthy mothers were collected for this purpose. The most
      relevant finding was the detection of the intact bovine alpha-S1-casein in both
      term and preterm colostrum. Using this method, which allows direct proteins
      identification, beta-lactoglobulin was not detected in any of colostrum samples.
      According to our results bovine alpha 1 casein that is considered a major cow's
      milk allergen is readily secreted in human milk: further investigations are
      needed in order to clarify if alpha-1-casein has a major role in sensitization or
      tolerance to cow's milk of exclusively breastfed predisposed infants.

PMID- 23158514
TI  - Higher protein intake strategies in human milk fortification for preterms infants
      feeding. Auxological and neurodevelopmental outcome.
AB  - Postnatal growth restriction and failure to thrive still remain a major problem
      in Extremely Low Birth Weight (ELBW) infants . The goal for the nutritional care
      of these infants is to achieve rate of growth similar to those of the fetus in
      utero at the equivalent gestational age. Human milk fortified remains the best
      food for all these preterms. Two groups of preterm of weight 580-1250 g and
      gestational age 23-32 wk, were fed with different protein intake in the
      human/maternal milk fortified ( 3,5 g Kg-1 per day and 4,8 g Kg-1 per day in the
      control and intervention group respectively).The feeding tolerance, intrahospital
      growth, neurological outcome and anthropometric data until 12 months of corrected
      age, were evaluated. The protein supplemented group (PSG) showed an intrahospital
      highter growth rate ( mostly in head circumference, p 0,02, and length growth, p
      0,04) only in the preterms with 580-980 g and 23-30 wk. In the same preterms,
      Griffith Development Mental Score at 3 and 12 months corrected age showed higher
      score than in the control group in the Performance (p 0,04) and Hearing/Language
      (p 0,03) items. The auxological evaluation in the postdischarge period showed in
      the PSG group mean z-score values for length higher than those in the control
      group at 9 (p 0,04) months of corrected age.

PMID- 23158515
TI  - Early neutral prebiotic oligosaccharide supplementation reduces the incidence of
      some allergic manifestations in the first 5 years of life.
AB  - BACKGROUND: A mixture of neutral prebiotic oligosaccharides has been shown to
      reduce the incidence of atopic dermatitis (AD) and allergy associated symptoms
      during the first 2 years of life. OBJECTIVE: To evaluate if this protective
      effect against allergy lasted beyond the intervention period until 5 y of age.
      METHODS: In a prospective, double blind, placebo-controlled fashion, healthy term
      infants at risk of atopy were fed either a prebiotic-supplemented (0.8 g/100 ml
      scGOS/lcFOS) or placebo-supplemented (0.8 g/100 ml maltodextrin) hypoallergenic
      formula during the first 6 mo of life. Following this intervention period, follow
      up continued until 5 y of life. The present study evaluated (i) the cumulative
      incidence of allergic manifestations during 5 y, and (ii) the prevalence of
      allergic and persistent allergic manifestations at 5 y. Monitored allergic
      manifestations were AD, recurrent wheezing, allergic rhinoconjunctivitis and
      urticaria. RESULTS: Ninety-two children (50 in placebo group, 42 in intervention
      group) completed the 5-y follow-up. The 5-y cumulative incidences of any allergic
      manifestation and atopic dermatitis were significantly lower in the scGOS/lcFOS
      group (30.9, 19.1 %, respectively) compared to placebo group (66, 38 %,
      respectively) (p< 0.01 and< 0.05). Children in the scGOS/lcFOS group tended to
      have a lower incidence of allergic rhinoconjunctivitis, and allergic urticaria
      (4.8 vs 16% for both manifestations, p=0.08). There was no difference in the
      cumulative incidence of recurrent wheezing. With regard to the prevalences at 5
      y, intervention group had significantly lower prevalence of any persistent
      allergic manifestation and rhinoconjunctivitis (4.8, 2.4 %, respectively)
      compared to placebo (26, 14 %, respectively) (p < 0.01 and =0.05). Prevalence of
      persistent AD tended to be lower in the intervention group (2.4 vs 12%, p= 0.09).
      Although intervention group had 75% reduction in the prevalence of persistent
      wheezing (4.8 vs 14 %), no significance was shown. CONCLUSION: Oligosaccharide
      prebiotics (scGOS/lcFOS), when started early in life have a protective effect
      against allergic manifestations in high risk infants. The protection lasts beyond
      infancy until 5 y of life, for AD and allergic rhinoconjunctivitis. Long-term
      follow-up studies in larger populations are warranted to evaluate the potential
      preventive effect of this mixture on asthma.

PMID- 23158516
TI  - Amendment to 2010 Italian guidelines for the establishment and operation of a
      donor human milk bank.
AB  - The present paper is an amendment to the recent Italian Guidelines of human milk
      banking published in 2010. Working Group on Guidelines (Panel) of the Italian
      Association of Human Milk Banks (AIBLUD) states, in accordance with the European
      Union Comission's Amending Directive of January 2011, that the hard plastic
      feeding bottles used in the collection, storage and pasteurization of the human
      milk should be Bisphenol A (BPA) free. Until new evidence are available
      polycarbonate feeding bottles should not be used for collection, storage and
      pasteurization of human milk. The paper summarizes the former and current
      European Commission Directives and shows the related amending changes to the 2010
      Italian Human Milk Banking Guidelines.

PMID- 23158517
TI  - Update of adjustable fortification regimen for preterm infants: a new protocol.
AB  - Preterm infants fed fortified human milk in standard fashion receive less protein
      than they need due to customary assumptions. Protein is limiting for growth and
      neurocognitive development,and shortfalls of protein are not acceptable.
      Adjustable fortification regimen has been proven as an effective way to provide
      adequate protein intakes and appropriate growth in this group of infants. Italian
      Association of Human Milk Banks (AIBLUD) has promoted and implemented this
      Adjustable fortification regimen in neonatal intensive care units (NICUs) with
      success. This paper presents an update of Adjustable fortification regimen; a new
      protocol already utilized in several italian NICUs.

PMID- 23158518
TI  - Early enteral feeding with human milk for VLBW infants.
AB  - In a NICU early enteral feeding is usually possible only when the newborn
      clinical conditions permit it. Because of the frequent need of umbilical/central
      catheters, they usually start with parenteral feeding and/or with minimal enteral
      feeding (trophic feeding). This kind of management is even more frequent in
      VLBWIs, in which the risk of NEC is very high. In this work we describe a model
      of early enteral exclusive feeding (EEEF) based on the use of banking human milk
      followed by mother milk. In the Centre of Neonatology of Trento, as in other
      Centers, the newborns weighing less than 750g or with a GE< 27 weeks, are treated
      with parenteral nutrition and minimal enteral feeding. The newborn weighing 750
      1249g and with GE > 26 weeks define a group in which we find critical neonates,
      who can not be treated with enteral feeding, and neonates whose clinical
      conditions permit EEEF. In particular, in a period of 16 years (1994-2009) in
      Trento, 308 newborns weighing 750-1249 g and GE > than 26 weeks were admitted.
      The 90,9 % has been treated with prenatal steroids, the 91,9 % was inborn, the
      96,1% survived. In the 59,1 % of the cases (175) we gave EEEF. We could continue
      with a complete EEEF in the 40,2 % of the total (119 cases). The characteristics
      of these neonates and our centre management, based mainly on early use of banking
      human milk and mother milk, are detailed described.

PMID- 23158519
TI  - Tolerability of donkey's milk in 92 highly-problematic cow's milk allergic
      children.
AB  - OBJECTIVE: Not exclusively breastfed children with cow's milk allergy (CMA)
      require a formula or other alternative food, but past and present guidelines
      differ concerning the best choice. Our aim was to investigate the clinical
      tolerability, palatability and nutritional adequacy of donkey's milk (DM) in
      children with proven CMA. It was important to identify a CM replacement for these
      children, highly problematic from the feeding standpoint, in spite of their age.
      STUDY DESIGN: A prospective study was conducted on 92 children with CMA,
      diagnosed through a CM elimination diet, followed by double-blind, placebo
      controlled food challenge (DBPCFC) unless contraindicated. Maternal milk was
      unavailable and current CM substitutes could not be used. Moreover, 89 percent
      were affected by multiple FA, and subjected to very restricted diets. Within 3
      months after the last CM challenge, DBPCFC for DM was performed. CM or DM skin
      prick test and sIgE determination preceded the CM or DM challenge, respectively.
      Native electrophoresis and immunoblotting were used to identify CM and DM cross
      reactive proteins. Z-scores of weight and length/stature for age were calculated
      at DM food challenge (T0) and during DM assumption. RESULTS: 83 children (90.2
      percent) liked and tolerated DM, at challenge and during follow-up, with
      increased Z-score for weight and length/stature and improved nutritional
      parameters. Bovine beta-lactoglobulin was identified as the cross-reacting
      protein among the DM allergic patients. CONCLUSIONS: DM was found to be a valid
      alternative foodstuff, in terms of clinical tolerability, palatability and
      nutritional adequacy, in subjects with CMA who were highly problematic from the
      feeding standpoint.

PMID- 23158520
TI  - Relationship between sleep/wakefulness and gastroesophageal reflux in symptomatic
      newborns.
AB  - The state of sleep/wakefulness is well known to influence esophageal acid
      exposure and the number of acid refluxes whereas it is uncertain whether the same
      is true of the non-acid refluxes that predominate in the newborns. To investigate
      the relationship between sleep/wakefulness and refluxes 45 newborns with
      gastroesophageal reflux symptoms were studied with combined multichannel
      intraluminal impedance and pH monitoring. We found that sleep/wakefulness
      influenced acid and weakly acidic reflux frequency (awake 2.6+/-0.8; asleep 2.1+/
      1.1; p=0.006). A negative correlation was found between sleepness periods and the
      mean reflux duration for both acid (R=0.55;p < 0.001) and weackly acidic
      (R=0.51;p < 0.001) refluxes. This finding may raise some concerns about the over
      prescription of antacid drugs in newborns.

PMID- 23158521
TI  - Everolimus for astrocytomas in tuberous sclerosis complex.

PMID- 23158522
TI  - Efficacy and safety of everolimus for subependymal giant cell astrocytomas
      associated with tuberous sclerosis complex (EXIST-1): a multicentre, randomised,
      placebo-controlled phase 3 trial.
AB  - BACKGROUND: Tuberous sclerosis complex is a genetic disorder leading to
      constitutive activation of mammalian target of rapamycin (mTOR) and growth of
      benign tumours in several organs. In the brain, growth of subependymal giant cell
      astrocytomas can cause life-threatening symptoms--eg, hydrocephalus, requiring
      surgery. In an open-label, phase 1/2 study, the mTOR inhibitor everolimus
      substantially and significantly reduced the volume of subependymal giant cell
      astrocytomas. We assessed the efficacy and safety of everolimus in patients with
      subependymal giant cell astrocytomas associated with tuberous sclerosis complex.
      METHODS: In this double-blind, placebo-controlled, phase 3 trial, patients (aged
      0-65 years) in 24 centres in Australia, Belgium, Canada, Germany, the UK, Italy,
      the Netherlands, Poland, Russian Federation, and the USA were randomly assigned,
      with an interactive internet-response system, in a 2:1 ratio to oral everolimus
      4.5 mg/m(2) per day (titrated to achieve blood trough concentrations of 5-15
      ng/mL) or placebo. Eligible patients had a definite diagnosis of tuberous
      sclerosis complex and at least one lesion with a diameter of 1 cm or greater, and
      either serial growth of a subependymal giant cell astrocytoma, a new lesion of 1
      cm or greater, or new or worsening hydrocephalus. The primary endpoint was the
      proportion of patients with confirmed response--ie, reduction in target volume of
      50% or greater relative to baseline in subependymal giant cell astrocytomas.
      Analysis was by intention to treat. This study is registered with
      ClinicalTrials.gov, number NCT00789828. FINDINGS: 117 patients were randomly
      assigned to everolimus (n=78) or placebo (n=39). 27 (35%) patients in the
      everolimus group had at least 50% reduction in the volume of subependymal giant
      cell astrocytomas versus none in the placebo group (difference 35%, 95% CI 15-52;
      one-sided exact Cochran-Mantel-Haenszel test, p<0.0001). Adverse events were
      mostly grade 1 or 2; no patients discontinued treatment because of adverse
      events. The most common adverse events were mouth ulceration (25 [32%] in the
      everolimus group vs two [5%] in the placebo group), stomatitis (24 [31%] vs eight
      [21%]), convulsion (18 [23%] vs ten [26%]), and pyrexia (17 [22%] vs six [15%]).
      INTERPRETATION: These results support the use of everolimus for subependymal
      giant cell astrocytomas associated with tuberous sclerosis. Additionally,
      everolimus might represent a disease-modifying treatment for other aspects of
      tuberous sclerosis. FUNDING: Novartis Pharmaceuticals.

PMID- 23158524
TI  - Assessment of the effects of forest land use strategies on the provision of
      ecosystem services at regional scale.
AB  - This paper presents results of a case study in Middle Saxony, Germany, where the
      impact of conversion, afforestation and alternatively introduction of short
      rotation coppice areas on the provision of ecosystem services was tested in a
      spatially inexplicit and a spatially explicit way to formulate recommendations
      for regional planning. While the spatially inexplicit testing did not lead to
      clear results regarding to what degree forests or short rotation coppice areas
      are desirable and applicable, the spatially explicit testing revealed that an
      increase in the forest area or area with short rotation coppice by 29.7% in
      unstructured agriculturally dominated Loess regions, 14.4% in more
      topographically structured parts in the North-East of the model region and 23.6%
      in its mountainous parts would be beneficial. Potentially resulting losses in the
      provision of bioresources and regional economy can be considerably reduced by
      replacing afforestation areas with short rotation coppice. In summary, we found
      that the spatially explicit analysis of land use scenarios in combination with a
      more detailed land use classification and including an assessment of changes in
      land use pattern gave us an improved basis for assessing different possible
      planning strategies and to enhance the communication between forest management
      planners and regional planners. 

PMID- 23158523
TI  - InSilico DB genomic datasets hub: an efficient starting point for analyzing
      genome-wide studies in GenePattern, Integrative Genomics Viewer, and
      R/Bioconductor.
AB  - Genomics datasets are increasingly useful for gaining biomedical insights, with
      adoption in the clinic underway. However, multiple hurdles related to data
      management stand in the way of their efficient large-scale utilization. The
      solution proposed is a web-based data storage hub. Having clear focus,
      flexibility and adaptability, InSilico DB seamlessly connects genomics dataset
      repositories to state-of-the-art and free GUI and command-line data analysis
      tools. The InSilico DB platform is a powerful collaborative environment, with
      advanced capabilities for biocuration, dataset sharing, and dataset subsetting
      and combination. InSilico DB is available from https://insilicodb.org. 

PMID- 23158525
TI  - Channelling science into policy: enabling best practices from research on land
      degradation and sustainable land management in dryland Africa.
AB  - Demands are increasing for scientific research to be explicitly and demonstrably
      policy relevant. Research funders are requiring greater returns on their
      investments and scientists are expected to demonstrate clearly how their research
      can inform policy and regulation to deliver positive consequences for societal,
      economic and environmental wellbeing. Within the co-evolving context of
      environmental management research in dryland Africa and the policy approaches
      designed to mitigate land degradation, few academic analyses have deconstructed
      the practical 'bottom-up' actions that can help to channel scientific research
      into national decision-making and policy. Similarly, while international
      platforms developed by the United Nations Convention to Combat Desertification
      have started to facilitate greater knowledge exchange between scientists and
      policymakers, analyses have failed to consider the powerful informal actions that
      scientists can take to allow their research to inform evidence-based
      international policy. Drawing on examples in the literature from research on land
      degradation and sustainable land management across sub-Saharan African drylands,
      we identify key enabling activities that help make scientific research more
      visible, accessible to, and compatible with, policy processes at local, national
      and international levels. We argue that these enablers are applicable to other
      environmental research areas beyond land degradation, and suggest that improved
      understanding of science into policy processes that look across multiple scales
      and levels will help researchers and policy-makers to better match information
      supply and demand to the mutual benefit of both groups.

PMID- 23158526
TI  - Pathogenesis of acute coronary syndromes.
AB  - Experimental models of atherogenesis have provided a growing body of information
      about molecular mechanisms of plaque growth; however, transition from coronary
      stability to instability is less well understood due to the lack of animal models
      reflective of human disease. The abrupt clinical presentation of acute coronary
      syndromes gives a strong signal of discontinuity in the natural history of
      atherothrombosis. The causes of such discontinuity are complex, probably
      multiple, and still largely unknown. A better knowledge of the causes of coronary
      instability might allow identification of new therapeutic targets aimed at the
      preservation of plaque stability in those subjects in whom primary prevention
      fails to prevent plaque growth. The goal of this review was to propose a
      pathogenetic classification of acute coronary syndromes that might help in the
      search of new diagnostic algorithms and therapeutic targets.

PMID- 23158527
TI  - Myocardial recovery and the failing heart: myth, magic, or molecular target?
AB  - Medical and device therapies that reduce heart failure morbidity and mortality
      also lead to decreased left ventricular volume and mass and a more normal
      elliptical shape of the ventricle. These are due to changes in myocyte size,
      structure, and organization that have been referred to collectively as reverse
      remodeling. Moreover, there are subsets of patients whose hearts have undergone
      reverse remodeling either spontaneously or after medical or device therapies and
      whose clinical course is associated with freedom from future heart failure
      events. This phenomenon has been referred to as myocardial recovery. Despite the
      frequent interchangeable use of the terms "myocardial recovery" and "reverse
      remodeling" to describe the reversal of various aspects of the heart failure
      phenotype after medical and device therapy, the literature suggests that there
      are important differences between these 2 phenomena and that myocardial recovery
      and reverse remodeling are not synonymous. In this review, we discuss the biology
      of cardiac remodeling, cardiac reverse remodeling, and myocardial recovery with
      the intent to provide a conceptual framework for understanding myocardial
      recovery.

PMID- 23158528
TI  - Physical activity, change in biomarkers of myocardial stress and injury, and
      subsequent heart failure risk in older adults.
AB  - OBJECTIVES: The aim of this study was to evaluate the association between
      physical activity and changes in levels of highly sensitive troponin T (cTnT) and
      N-terminal pro-B-type natriuretic peptide (NT-proBNP), and the subsequent risk of
      the development of heart failure (HF) in community-dwelling older adults.
      BACKGROUND: Higher baseline levels of cTnT and NT-proBNP and increases over time
      correlate with the risk of HF in older adults. Factors modifying these levels
      have not been identified. METHODS: NT-proBNP and cTnT were measured at baseline
      and 2 to 3 years later in adults 65 years of age and older free of HF
      participating in the Cardiovascular Health Study. Self-reported physical activity
      and walking pace were combined into a composite score. An increase was
      prespecified for NT-proBNP as a >25% increment from baseline to >=190 pg/ml and
      for cTnT as a >50% increment from baseline in participants with detectable levels
      (>=3 pg/ml). RESULTS: A total of 2,933 participants free of HF had NT-proBNP and
      cTnT measured at both time points. The probability of an increase in biomarker
      concentrations between baseline and follow-up visits was inversely related to the
      physical activity score. Compared with participants with the lowest score, those
      with the highest score had an odds ratio of 0.50 (95% confidence interval: 0.33
      to 0.77) for an increase in NT-proBNP and an odds ratio of 0.30 (95% confidence
      interval: 0.16 to 0.55) for an increase in cTnT, after adjusting for
      comorbidities and baseline levels. A higher activity score associated with a
      lower long-term incidence of HF. Moreover, at each level of activity, an increase
      in either biomarker still identified those at higher risk. CONCLUSIONS: These
      findings suggest that moderate physical activity has protective effects on early
      heart failure phenotypes, preventing cardiac injury and neurohormonal activation.

PMID- 23158529
TI  - Cardiac positron emission tomography/computed tomography imaging of the Renin
      Angiotensin system in humans holds promise for image-guided approach to heart
      failure therapy.

PMID- 23158530
TI  - A randomized multicenter study comparing a paclitaxel drug-eluting balloon with a
      paclitaxel-eluting stent in small coronary vessels: the BELLO (Balloon Elution
      and Late Loss Optimization) study.
AB  - OBJECTIVES: The aim of this study was to evaluate the efficacy of drug-eluting
      balloons (DEB) compared with paclitaxel-eluting stents (PES) for the reduction of
      restenosis in small vessels. BACKGROUND: DEB have been shown to be effective in
      the treatment of coronary in-stent restenosis, but data are limited regarding
      their efficacy in de novo disease. METHODS: BELLO (Balloon Elution and Late Loss
      Optimization) is a prospective, multicenter trial that randomized 182 patients
      with lesions located in small vessels (reference diameter <2.8 mm) to treatment
      with paclitaxel DEB and provisional bare-metal stenting (n = 90) or PES
      implantation (n = 92). The primary endpoint was noninferiority of angiographic in
      stent (in-balloon) late loss with a delta of 0.25 mm. Secondary endpoints were
      angiographic restenosis, target lesion revascularization, and major adverse
      cardiac events (MACE; death, myocardial infarction, target vessel
      revascularization) at 6 months. RESULTS: Baseline characteristics were well
      matched, except for a smaller vessel size in the DEB group (2.15 +/- 0.27 mm vs.
      2.25 +/- 0.24 mm; p = 0.003). The majority (89%) of lesions involved vessels with
      a diameter <2.5 mm. Bailout stenting was required in 20% of lesions in the DEB
      group. The primary endpoint of in-stent (in-balloon) late loss was significantly
      less with DEB compared with PES (0.08 +/- 0.38 mm vs. 0.29 +/- 0.44 mm;
      difference -0.21; 95% CI: -0.34 to -0.09; p(noninferiority) < 0.001;
      p(superiority) = 0.001). At 6 months, DEB and PES were associated with similar
      rates of angiographic restenosis (10% vs. 14.6%; p = 0.35), [corrected] target
      lesion revascularization (4.4% vs. 7.6%; p = 0.37), and MACE (10% vs. 16.3%; p =
      0.21). [corrected]. CONCLUSIONS: Treatment of small-vessel disease with a
      paclitaxel DEB was associated with less angiographic late loss and similar rates
      of restenosis and revascularization as a PES. (Balloon Elution and Late Loss
      Optimization [BELLO]; Study NCT01086579).

PMID- 23158531
TI  - Vagal reflexes following an exercise stress test: a simple clinical tool for gene
      specific risk stratification in the long QT syndrome.
AB  - OBJECTIVES: The study assessed whether heart rate (HR) reduction following an
      exercise stress test (ExStrT), an easily quantifiable marker of vagal reflexes,
      might identify high- and low-risk long QT syndrome (LQTS) type 1 (LQT1) patients.
      BACKGROUND: Identification of LQTS patients more likely to be symptomatic remains
      elusive. We have previously shown that depressed baroreflex sensitivity, an
      established marker of reduced vagal reflexes, predicts low probability of
      symptoms among LQT1. METHODS: We studied 169 LQTS genotype-positive patients < 50
      years of age who performed an ExStrT with the same protocol, on and off beta
      blockers including 47 South African LQT1 patients all harboring the KCNQ1-A341V
      mutation and 122 Italian LQTS patients with impaired (I(Ks)-, 66 LQT1) or normal
      (I(Ks)+, 50 LQT2 and 6 LQT3) I(Ks) current. RESULTS: Despite similar maximal HR
      and workload, by the first minute after cessation of exercise the symptomatic
      patients in both I(Ks)- groups had a greater HR reduction compared with the
      asymptomatic (19 +/- 7 beats/min vs. 13 +/- 5 beats/min and 27 +/- 10 beats/min
      vs. 20 +/- 8 beats/min, both p = 0.009). By contrast, there was no difference
      between the I(Ks)+ symptomatic and asymptomatic patients (23 +/- 9 beats/min vs.
      26 +/- 9 beats/min, p = 0.47). LQT1 patients in the upper tertile for HR
      reduction had a higher risk of being symptomatic (odds ratio: 3.28, 95%
      confidence interval: 1.3 to 8.3, p = 0.012). CONCLUSIONS: HR reduction following
      exercise identifies LQT1 patients at high or low arrhythmic risk, independently
      of beta-blocker therapy, and contributes to risk stratification. Intense exercise
      training, which potentiates vagal reflexes, should probably be avoided by LQT1
      patients.

PMID- 23158532
TI  - A new drug delivery system for intravenous coronary thrombolysis with thrombus
      targeting and stealth activity recoverable by ultrasound.
AB  - OBJECTIVES: The purpose of this study was to develop a new intelligent drug
      delivery system for intracoronary thrombolysis with a strong thrombolytic effect
      without increasing bleeding risk. BACKGROUND: Rapid recanalization of an occluded
      coronary artery is essential for better outcomes in acute myocardial infarction.
      Catheter-based recanalization is widely accepted, but it takes time to transport
      patients. Although the current fibrinolytic therapy can be started quickly, it
      cannot achieve a high reperfusion rate. Recently, we generated nanoparticles
      comprising tissue-type plasminogen activator (tPA), basic gelatin, and zinc ions,
      which suppress tPA activity by 50% with 100% recovery by ultrasound (US) in
      vitro. METHODS: The thrombus-targeting property of nanoparticles was examined by
      an in vitro binding assay with von Wilbrand factor and with a mouse arterial
      thrombosis model in vivo. The thrombolytic efficacy of nanoparticles was
      evaluated with a swine acute myocardial infarction model. RESULTS: Nanoparticles
      bound to von Wilbrand factor in vitro and preferentially accumulated at the site
      of thrombus in a mouse model. In a swine acute myocardial infarction model,
      plasma tPA activity after intravenous injection of nanoparticles was
      approximately 25% of tPA alone and was recovered completely by transthoracic US
      (1.0 MHz, 1.0 W/cm(2)). During US application, plasma tPA activity near the
      affected coronary artery was recovered and was higher than that near the femoral
      artery. Although treatment with tPA alone (55,000 IU/kg) recanalized the occluded
      coronary artery in only 1 of 10 swine, nanoparticles containing the same dose of
      tPA with US achieved recanalization in 9 of 10 swine within 30 min. CONCLUSIONS:
      We developed an intelligent drug delivery system with promising potential for
      better intravenous coronary thrombolysis.

PMID- 23158533
TI  - Molecular hybrid positron emission tomography/computed tomography imaging of
      cardiac angiotensin II type 1 receptors.
AB  - OBJECTIVES: The goal of this study was to explore the feasibility of targeted
      imaging of the angiotensin II type 1 receptor (AT1R) in cardiac tissue, using
      clinical hybrid positron emission tomography/computed tomography (PET/CT).
      BACKGROUND: AT1R is an attractive imaging target due to its key role in various
      cardiac pathologies, including post-infarct left ventricular remodeling. METHODS:
      Using the novel AT1R ligand [(11)C]-KR31173, dynamic PET/CT was performed in
      young farm pigs under healthy conditions (n = 4) and 3 to 4 weeks after
      experimental myocardial infarction (n = 5). Ex vivo validation was carried out by
      immunohistochemistry and polymerase chain reaction. First-in-man application was
      performed in 4 healthy volunteers at baseline and under AT1R blocking. RESULTS:
      In healthy pigs, myocardial KR31173 retention was detectable, regionally
      homogeneous, and specific for AT1R, as confirmed by blocking experiments.
      Metabolism in plasma was low (85 +/- 2% of intact tracer after 60 min). After
      myocardial infarction, KR31173 retention, corrected for regional perfusion,
      revealed AT1R up-regulation in the infarct area relative to remote myocardium,
      whereas retention was elevated in both regions when compared with myocardium of
      healthy controls (8.7 +/- 0.8% and 7.1 +/- 0.3%/min vs. 5.8 +/- 0.4%/min for
      infarct and remote, respectively, vs. healthy controls; p < 0.01 each).
      Postmortem analysis confirmed AT1R up-regulation in remote and infarct tissue.
      First-in-man application was safe, and showed detectable and specific myocardial
      KR31173 retention, albeit at a lower level than pigs (left ventricular average
      retention: 1.2 +/- 0.1%/min vs. 4.4 +/- 1.2%/min for humans vs. pigs; p = 0.04).
      CONCLUSIONS: Noninvasive imaging of cardiac AT1R expression is feasible using
      clinical PET/CT technology. Results provide a rationale for broader clinical
      testing of AT1R-targeted molecular imaging.

PMID- 23158534
TI  - Progression of heart failure from AHA/ACC stage A to stage B or even C: can we
      all agree we should try to prevent this from happening?

PMID- 23158535
TI  - Exercise and vagal reflex in long QT syndrome type 1.

PMID- 23158536
TI  - Incidence of heart failure or cardiomyopathy after adjuvant trastuzumab therapy
      for breast cancer.
AB  - OBJECTIVES: The purpose of this study was to estimate heart failure (HF) and
      cardiomyopathy (CM) rates after adjuvant trastuzumab therapy and chemotherapy in
      a population of older women with early-stage breast cancer. BACKGROUND: Newer
      biologic therapies for breast cancer such as trastuzumab have been reported to
      increase HF and CM in clinical trials, especially in combination with
      anthracycline chemotherapy. Elderly patients, however, typically have a higher
      prevalence of cardiovascular risk factors and have been underrepresented in
      trastuzumab clinical trials. METHODS: Using Surveillance, Epidemiology, and End
      Results-Medicare data from 2000 through 2007, we identified women 67 to 94 years
      of age with early-stage breast cancer. We calculated 3-year incidence rates of HF
      or CM for the following mutually exclusive treatment groups: trastuzumab (with or
      without nonanthracycline chemotherapy), anthracycline plus trastuzumab,
      anthracycline (without trastuzumab and with or without nonanthracycline
      chemotherapy), other nonanthracycline chemotherapy, or no adjuvant chemotherapy
      or trastuzumab therapy. HF or CM events were ascertained from administrative
      Medicare claims. Poisson regression was used to quantify risk of HF or CM,
      adjusting for sociodemographic factors, cancer characteristics, and
      cardiovascular conditions. RESULTS: We identified 45,537 older women (mean age:
      76.2 years, standard deviation: 6.2 years) with early-stage breast cancer.
      Adjusted 3-year HF or CM incidence rates were higher for patients receiving
      trastuzumab (32.1 per 100 patients) and anthracycline plus trastuzumab (41.9 per
      100 patients) compared with no adjuvant therapy (18.1 per 100 patients, p <
      0.001). Adding trastuzumab to anthracycline therapy added 12.1, 17.9, and 21.7 HF
      or CM events per 100 patients over 1, 2, and 3 years of follow-up, respectively.
      CONCLUSIONS: HF or CM are common complications after trastuzumab therapy for
      older women, with higher rates than those reported from clinical trials.

PMID- 23158537
TI  - Can we prevent heart failure with exercise?

PMID- 23158538
TI  - Protein therapeutics for cardiovascular disease: it is all about delivery.

PMID- 23158539
TI  - Fixed sized samples for type-specific surveillance of human papillomavirus in
      genital warts.
AB  - Surveillance data suggest that human papillomavirus (HPV) vaccination in
      Australia is reducing the incidence of genital warts. However, existing
      surveillance measures do not assess the proportion of the remaining cases of
      warts that are caused by HPV types other than 6 or 11, against which the vaccine
      has no demonstrated effectiveness. Using computer simulation rather than sample
      size formulae, we established that genotyping at least 60 warts can accurately
      test whether the proportion of warts due to HPV types not targeted by the vaccine
      has increased (Type I error probability <= 0.05, Type II error probability
      <0.07). Standard formulae for calculating sample size, in contrast, suggest that
      a sample size of more than 130 would be required for this task, but using these
      formulae entails making several strong assumptions. Our methods require fewer
      assumptions and demonstrate that a smaller sample size than anticipated could be
      used to address the question of what proportion of post-vaccination cases of
      warts are due to nonvaccine types. In conjunction with indications of incidence
      and prevalence provided by existing surveillance measures, this could indicate
      the number of cases of post-vaccination warts due to nonvaccine types and hence
      whether type replacement is occurring.

PMID- 23158540
TI  - Testing for Chlamydia trachomatis: time trends in positivity rates in the canton
      of Basel-Stadt, Switzerland.
AB  - National health statistics report a 2.5-fold increase in laboratory-confirmed
      Chlamydia trachomatis (CT) cases over the last decade in Switzerland where no CT
      screening programme exists. We obtained essential denominator information to
      describe the epidemiology of CT in the canton of Basel-Stadt, an urban canton in
      north-western Switzerland. Laboratories reporting at least two CT infections from
      Basel-Stadt residents to the SFOPH in 2010 provided demographic and test-related
      data. CT positivity rates were calculated for 2002-2010. The influences of test
      year, age, sex and laboratory on CT positivity were investigated in a
      multivariable model. Positivity differed between sexes and age groups. In our
      sample of 32 034 records, female and male CT positivity rates were 4.7% and
      11.1%, respectively. Test year was significantly associated with test outcome in
      the multivariable analysis but no time trend was observed. CT positivity did not
      change over the past 9 years in Basel-Stadt. In contrast to other European
      countries without CT screening, we found no evidence that the observed increase
      of Chlamydia cases in the national notification system represents an
      epidemiological trend, but rather results from an increased testing frequency.

PMID- 23158541
TI  - Molecular analysis of the carbapenem and metronidazole resistance mechanisms of
      Bacteroides strains reported in a Europe-wide antibiotic resistance survey.
AB  - Here we examine the carbapenem and metronidazole resistance mechanisms of 640
      Bacteroides strains reported in the 2008-2009 European antibiotic susceptibility
      survey. Of the 22 strains with elevated imipenem minimum inhibitory
      concentrations (>=4 MUg/mL), 10 were cfiA-positive and out of these 5 carried
      activating insertion sequence (IS) elements in the upstream regions of the cfiA
      genes. However, resistant strains with cfiA genes but with no activating IS
      elements were found (n=2) as well as a resistant strain with no cfiA gene. In the
      former the resistance phenotypes by Etest were heterogeneous, whilst in the
      latter no carbapenemase production was seen; both mechanisms have been rarely
      observed, examined and characterised. Interestingly, few (n=3) nim-positive
      strains were found, including one metronidazole-resistant strain harbouring nimE
      activated by ISBf6, and two susceptible strains harbouring chromosomally located
      nim genes.

PMID- 23158542
TI  - Genomic profiling of rectal adenoma and carcinoma by array-based comparative
      genomic hybridization.
AB  - BACKGROUND: Rectal cancer is one of the most common cancers in the world. Early
      detection and early therapy are important for the control of death caused by
      rectal cancer. The present study aims to investigate the genomic alterations in
      rectal adenoma and carcinoma. METHODS: We detected the genomic changes of 8
      rectal adenomas and 8 carcinomas using array CGH. Then 14 genes were selected for
      analyzing the expression between rectal tumor and paracancerous normal tissues as
      well as from adenoma to carcinoma by real-time PCR. The expression of GPNMB and
      DIS3 were further investigated in rectal adenoma and carcinoma tissues by
      immunohistochemistry. RESULTS: We indentified ten gains and 22 losses in rectal
      adenoma, and found 25 gains and 14 losses in carcinoma. Gains of 7p21.3-p15.3,
      7q22.3-q32.1, 13q13.1-q14.11, 13q21.1-q32.1, 13q32.2-q34, 20p11.21 and 20q11.23
      q12 and losses of 17p13.1-p11.2, 18p11.32-p11.21 and 18q11.1-q11.2 were shared by
      both rectal adenoma and carcinoma. Gains of 1q, 6p21.33-p21.31 and losses of
      10p14-p11.21, 14q12-q21.1, 14q22.1-q24.3, 14q31.3-q32.1, 14q32.2-q32.32, 15q15.1
      q21.1, 15q22.31 and 15q25.1-q25.2 were only detected in carcinoma but not in
      adenoma. Copy number and mRNA expression of EFNA1 increased from rectal adenoma
      to carcinoma. C13orf27 and PMEPA1 with increased copy number in both adenoma and
      carcinoma were over expressed in rectal cancer tissues. Protein and mRNA
      expression of GPNMB was significantly higher in cancer tissues than rectal
      adenoma tissues. CONCLUSION: Our data may help to identify the driving genes
      involved in the adenoma-carcinoma progression.

PMID- 23158543
TI  - Effects of rainfall on microbial water quality on Qingdao No. 1 Bathing Beach,
      China.
AB  - Limited by sampling frequency and detection methods, current recreational water
      monitoring programs often fail to protect public health, especially after heavy
      rain or flooding, when microbial water quality can change rapidly. In order to
      assess the variations in the microbial indicators and to develop a scientific
      warning system, we conducted an intensive sampling project at the No. 1 Bathing
      Beach. The results show that, during dry weather, the detection rate of
      Enterococcus was significantly lower than that of Faecal coliform bacteria. On
      these days, water quality was mainly impacted by pollutants brought in by
      swimmers than by stormwater outfall. During wet weather, rainfall and microbial
      bacterial concentrations showed a positive correlation. Trends in the two
      microbial bacteria were approximately the same. With increasing distance from the
      shore, the detection rate of microbial bacteria gradually decreased. Microbial
      bacteria concentrations increased markedly during high tide and under a south
      wind.

PMID- 23158544
TI  - The use of the iCare tonometer reduced the need for anesthesia to measure
      intraocular pressure in children.
AB  - PURPOSE: To determine whether the introduction of iCare rebound tonometry in a
      pediatric ophthalmology clinic resulted in fewer examinations under anesthesia to
      evaluate children with glaucoma. METHODS: The medical records of consecutive
      glaucoma patients were retrospectively reviewed. The numbers of examinations
      under anesthesia (EUAs) and office visits that included measurement of
      intraocular pressure (IOP) were compared for three periods relative to
      introduction of the Icare (Icare Finland Oy, Helsinki, Finland) rebound tonometer
      into our clinical practice: before device introduction, learning/transition
      period, and routine use. RESULTS: A total of 87 subjects were included: 48
      subjects met inclusion criteria for the first period; 58 patients met inclusion
      criteria for the third period (some subjects straddled all three periods). The
      average patient age for the first period was 4.2 years and 4.9 years (P = 0.3)
      for the third period. The number of EUAs performed before the introduction of the
      Icare was 55 and after the introduction of the Icare was 18 (P < 0.001). The
      number of office visits at which IOP was measured increased from 34 to 151 (P <
      0.001). Data from the transition period suggest a trend and a short learning
      period. CONCLUSIONS: The use of Icare tonometry decreased the need for EUAs to
      evaluate children with glaucoma and significantly increased successful IOP
      measurement in clinic.

PMID- 23158545
TI  - Re: Graded anterior transposition of the inferior oblique muscle for V-pattern
      strabismus.

PMID- 23158546
TI  - Re: Graded anterior transposition of the inferior oblique muscle for V-pattern
      strabismus.

PMID- 23158547
TI  - Superior limbic keratoconjunctivitis causing chronic ocular irritation in a
      child.
AB  - Superior limbic keratoconjunctivitis (SLK) is an uncommon, painful inflammation
      of the ocular surface localized to the superior sectors of the cornea, limbus,
      and conjunctiva. The clinical course tends to be chronic, with alternating
      periods of remission and exacerbation. Many patients experience severe ocular
      discomfort for long periods. Corneal involvement may induce scarring,
      astigmatism, and ultimately decreased vision. SLK typically occurs in woman
      between 20 and 60 years of age. Little is known about the features of SLK in
      young children because the earliest age described in the literature is
      adolescence. We report the clinical presentation and management of SLK in a 7
      year-old boy who responded well to topical steroids and lubricants.

PMID- 23158548
TI  - External ophthalmoplegia in human immunodeficiency virus-infected patients
      receiving antiretroviral therapy.
AB  - BACKGROUND: On rare occasions, patients infected with human immunodeficiency
      virus (HIV) can develop a disorder similar to chronic progressive external
      ophthalmoplegia (CPEO) while undergoing long-term treatment with antiretroviral
      therapy. Orbital imaging may help explain the pathogenesis of this abnormality.
      METHODS: In this case series, 5 adult patients who presented with a CPEO-like
      disorder after more than 10 years of antiretroviral therapy and who underwent T1
      weighted high-resolution magnetic resonance imaging (MRI) of the orbits and brain
      were retrospectively identified. Patients also were screened for acetylcholine
      receptor antibody levels. RESULTS: All patients had bilateral external
      ophthalmoplegia and blepharoptosis. Acetylcholine receptor antibody titers were
      not increased. Brain MRI was unremarkable. Orbital MRI showed patchy bright
      signal inside the extraocular muscles that had conserved volume. CONCLUSIONS:
      Patients with HIV under long-term antiretroviral therapy may develop functional
      abnormalities of extraocular muscles that are structurally normal in size, that
      is, changes are similar to those observed in the orbital MRIs of patients with
      CPEO. This constellation of signs and symptoms suggests a possible role of HIV
      disease or antiretroviral therapy in the CPEO-like syndrome observed in some HIV
      infected individuals.

PMID- 23158549
TI  - CYP1B1 analysis of unilateral primary newborn glaucoma in Saudi children.
AB  - Nonsyndromic primary newborn glaucoma, the most severe form of primary congenital
      glaucoma, typically is bilateral and often the result of CYP1B1 mutations,
      particularly in certain consanguineous populations. Truly unilateral cases are
      uncommon and genetically not well studied. During a 9-year period, we tested 5
      consecutive children with unilateral primary newborn glaucoma from Saudi Arabia,
      where CYP1B1 mutations are the cause for 91% of bilateral primary newborn
      glaucoma cases. None of these children with unilateral primary newborn glaucoma
      harbored CYP1B1 mutations, suggesting that in this population the pathogenesis of
      unilateral disease differs from that of bilateral disease.

PMID- 23158550
TI  - Surgical management of a patient with exercise-induced esotropia.
AB  - Exercise-induced esotropia is a rare form of strabismus characterized by
      paroxysms of esotropia and diplopia only during exercise. This report describes a
      15-year-old boy who presented with a 1-year history of exercise-induced
      esotropia. He has been asymptomatic after recession of a single medial rectus
      muscle. It is hypothesized that the esotropia was attributable to a malfunction
      in the muscle tension-control circuit and that altering the small signal gain
      with surgery resulted in improvement.

PMID- 23158551
TI  - Strabismus among aged fee-for-service Medicare beneficiaries.
AB  - PURPOSE: To describe the prevalence of strabismus and strabismus surgery in the
      aged Medicare fee-for-service population. METHODS: A 5% random sample of Medicare
      Part B physician claims was used to identify beneficiaries >= 65 years of age
      with strabismus and those undergoing strabismus surgery between 2002 and 2010.
      RESULTS: In 2010 there were 1,237,469 beneficiaries. The diagnosis of strabismus
      was made in 8,470 (0.68%), more often in females (56%) and in whites (92%).
      Common diagnoses were paralytic strabismus, exotropia, and esotropia, with each
      reported in 22%. Strabismus surgery in 2010 was performed on 197 patients (0.016%
      of all beneficiaries), or approximately 2.3% of patients with the diagnosis of
      strabismus. Horizontal surgical codes were reported most frequently (68%).
      Reoperations were reported for 23% and adjustable sutures for 23% of cases. The
      prevalence of strabismus surgery ranged from 183 to 236 cases annually (0.015%
      0.018%). Review of pooled data (2002-2010) found that the prevalence of
      strabismus increased with age from 65 to 89 years of age (P < 0.0001) and that
      whites underwent strabismus surgery more often than African Americans (0.017% vs
      0.007%, respectively; P < 0.0001). CONCLUSIONS: Less than 1% of aged Medicare
      beneficiaries are diagnosed with strabismus each year, with the rate increasing
      significantly with age. Strabismus surgery is performed annually in 16 of 100,000
      of aged Medicare beneficiaries; the surgery rate is significantly lower among
      African Americans. Understanding the reasons for the difference by race/ethnicity
      deserve further study.

PMID- 23158552
TI  - Newborn primary congenital glaucoma: histopathologic features of the anterior
      chamber filtration angle.
AB  - We present histopathologic findings that have not been previously reported as
      associated with abnormalities of the anterior chamber angle underlying newborn
      primary congenital glaucoma as a distinct entity. The major histopathologic
      findings were partial absence and retrodisplacement of Schlemm's canal,
      hypoplasia of the trabecular meshwork, broad attachment of ciliary muscle to the
      meshwork, and anterior insertion of hypoplastic iris with the formation of a
      pseudomembrane. These profound anatomic derangements explain why goniosurgery is
      frequently unsuccessful in cases of newborn glaucoma.

PMID- 23158553
TI  - Primary synovial sarcoma in the orbit.
AB  - Synovial sarcoma is a rare malignant neoplasm that accounts for approximately 6%
      to 9% of all soft-tissue tumors. It occurs predominately in upper and lower
      extremities of young adults. We report the first case of a primary orbital
      synovial sarcoma in an 18-month-old girl.

PMID- 23158554
TI  - Geographical access to care at birth in Ghana:  a barrier to safe motherhood.
AB  - BACKGROUND: Appropriate facility-based care at birth is a key determinant of safe
      motherhood but geographical access remains poor in many high burden regions.
      Despite its importance, geographical access is rarely audited systematically,
      preventing integration in national-level maternal health system assessment and
      planning. In this study, we develop a uniquely detailed set of spatially-linked
      data and a calibrated geospatial model to undertake a national-scale audit of
      geographical access to maternity care at birth in Ghana, a high-burden country
      typical of many in sub-Saharan Africa. METHODS: We assembled detailed spatial
      data on the population, health facilities, and landscape features influencing
      journeys. These were used in a geospatial model to estimate journey-time for all
      women of childbearing age (WoCBA) to their nearest health facility offering
      differing levels of care at birth, taking into account different transport types
      and availability. We calibrated the model using data on actual journeys made by
      women seeking care. RESULTS: We found that a third of women (34%) in Ghana live
      beyond the clinically significant two-hour threshold from facilities likely to
      offer emergency obstetric and neonatal care (EmONC) classed at the 'partial'
      standard or better. Nearly half (45%) live that distance or further from
      'comprehensive' EmONC facilities, offering life-saving blood transfusion and
      surgery. In the most remote regions these figures rose to 63% and 81%,
      respectively. Poor levels of access were found in many regions that meet
      international targets based on facilities-per-capita ratios. CONCLUSIONS:
      Detailed data assembly combined with geospatial modelling can provide nation-wide
      audits of geographical access to care at birth to support systemic maternal
      health planning, human resource deployment, and strategic targeting. Current
      international benchmarks of maternal health care provision are inadequate for
      these purposes because they fail to take account of the location and
      accessibility of services relative to the women they serve.

PMID- 23158555
TI  - Effects of babassu nut oil on ischemia/reperfusion-induced leukocyte adhesion and
      macromolecular leakage in the microcirculation: observation in the hamster cheek
      pouch.
AB  - BACKGROUND: The babassu palm tree is native to Brazil and is most densely
      distributed in the Cocais region of the state of Maranhao, in northeastern
      Brazil. In addition to the industrial use of refined babassu oil, the milk, the
      unrefined oil and the nuts in natura are used by families from several
      communities of African descendants as one of the principal sources of food
      energy. The objective of this study was to evaluate the effects of babassu oil on
      microvascular permeability and leukocyte-endothelial interactions induced by
      ischemia/reperfusion using the hamster cheek pouch microcirculation as
      experimental model. METHODS: Twice a day for 14 days, male hamsters received
      unrefined babassu oil (0.02 ml/dose [BO-2 group], 0.06 ml/dose [BO-6 group], 0.18
      ml/dose [BO-18 group]) or mineral oil (0.18 ml/dose [MO group]). Observations
      were made in the cheek pouch and macromolecular permeability increase induced by
      ischemia/reperfusion (I/R) or topical application of histamine, as well as
      leukocyte-endothelial interaction after I/R were evaluated. RESULTS: The mean
      value of I/R-induced microvascular leakage, determined during reperfusion, was
      significantly lower in the BO-6 and BO-18 groups than in the MO one (P < 0.001).
      In addition, histamine-induced increase of microvascular permeability was
      significantly less pronounced in BO groups compared to MO one. No significant
      differences among groups in terms of leukocyte adhesion, concentrations of tumor
      necrosis factor alpha, interleukin 1, and interleukin 6 were found. CONCLUSIONS:
      Our findings suggest that unrefined babassu oil reduced microvascular leakage and
      protected against histamine-induced effects in postcapillary venules and
      highlights that these almost unexploited nut and its oil might be secure sources
      of food energy.

PMID- 23158557
TI  - [Achieving individualized and multidisciplinary cancer care for brain gliomas].

PMID- 23158556
TI  - Association of dimethylarginines and mediators of inflammation after acute
      ischemic stroke.
AB  - BACKGROUND: Elevated levels of asymmetric dimethylarginine (ADMA) and symmetric
      dimethylarginine (SDMA) are accompanied by endothelial dysfunction and predict
      adverse outcome after ischemic stroke. Via induction of oxidative stress,
      dimethylarginines are possibly linked to the inflammatory cascade after stroke
      that is known to considerably contribute to secondary progression of brain
      injury. We sought to investigate the association between dimethylarginines and
      inflammatory mediators in patients with acute ischemic stroke. METHODS: Plasma
      levels of ADMA and SDMA were measured in prospectively collected blood samples of
      58 patients with acute ischemic stroke. Blood samples were taken at 6 hours, 12
      hours, 24 hours, 3 days and 7 days after onset of symptoms. Analyses of ADMA and
      SDMA were done by high-performance liquid chromatography-tandem mass
      spectrometry. Monocyte chemotactic protein-1 (MCP-1), matrix metalloproteinase-9
      (MMP-9), tissue inhibitor of matrix metalloproteinase-1 (TIMP-1), interleukin-6
      (IL-6), C-reactive protein (CRP) and S100B as markers of inflammation and brain
      damage were determined by commercially available immunometric assays. Patient
      data were compared with control data from 32 age-adjusted healthy volunteers.
      Baseline stroke severity was evaluated by the National Institutes of Health
      Stroke Scale (NIHSS) (NIHSS 0 to 1: mild stroke; NIHSS 2 to 8: moderate stroke;
      NIHSS >=9: severe stroke). RESULTS: Plasma ADMA and SDMA levels significantly
      correlated with blood levels of inflammatory mediators up to day 7 after stroke.
      On multiple stepwise linear regression analysis ADMA correlated with TIMP-1 at 6
      hours, 24 hours, 3 days and 7 days, MMP-9 at 12 hours and IL-6 at 7 days (P
      <0.05) while SDMA correlated with MCP-1 at 6 hours, 24 hours, 3 days and 7 days
      as well as IL-6 at 3 days and 7 days (P <0.05). CONCLUSIONS: The levels of the
      vasoactive compound ADMA as well as levels of its structural isomer SDMA are
      associated with levels of inflammatory mediators after acute ischemic stroke.
      Further studies need to elucidate the cause and effect relationship of these
      crucial players.

PMID- 23158558
TI  - [Analysis of recurrence patterns after curative resection of stage IIIA-N2 non
      small cell lung cancer].
AB  - OBJECTIVE: To explore the postoperative recurrence patterns in the patients
      undergoing potentially curative resection of stage IIIA-N2 non-small cell lung
      cancer (NSCLC). METHODS: A total of 63 patients underwent curative operation from
      September 2004 to December 2008 at Peking University First Hospital and were
      pathologically diagnosed as stage IIIA-N2 NSCLC. Their clinical data were
      retrospectively reviewed. The follow-ups were conducted to detect the recurrent
      lesions. The recurrence rates at Year 2-3 were calculated by the Kaplan-Meier
      method while the Cox proportional hazard model was used to assess the risk
      factors associated with recurrence. RESULTS: The 2 and 3-year recurrence rate was
      46.6% and 57.3% respectively. Only one patient experienced local failure.
      However, the predominant recurrence pattern was distant failure (27/28). As
      demonstrated by the univariate Cox regression analysis, 4 significant factors
      associated with recurrence and the arm of lymphatic or vascular invasion (LVI),
      number of positive N2 station > 1, number of positive node > 3 and involvement of
      subcarinal lymph nodes were found to increase the risks of failure (P < 0.05).
      CONCLUSION: Distant failure is the predominant pattern of postoperative
      recurrence in the patients of stage IIIA-N2 NSCLC. In addition to LVI, the level
      of positive N2 station, the number of positive N2 node and the involvement of
      subcarinal lymph nodes are associated with the postoperative risk of recurrence.

PMID- 23158559
TI  - [Ovarian ultrasonographic features in reproductive age females with polycystic
      ovary syndrome and the establishment of ultrasonographic criteria].
AB  - OBJECTIVE: To understand the ovarian ultrasound imaging features in the
      reproductive age females with polycystic ovary syndrome (PCOS). METHODS: A total
      of 396 PCOS patients aged 18 - 35 years were recruited from our gynaecology &
      endocrinology clinic, including obese (OB-PCOS group, n = 153) and non-obese (NOB
      PCOS group, n = 241). And 635 reproductive period females with normal
      menstruation for the control group, including obese (OB-CON group, n = 72) and
      non-obese (NOB-CON group, n = 563). Questionnaire surveys were conducted on their
      menstrual history. Vagina or rectum ultrasound methods were employed to determine
      the values of ovarian follicle number (FN) and ovarian volume (OV). Also the
      clinical symptom scores and endocrine and metabolic indices were measured.
      RESULTS: (1) As compared to the control group, the values of ovarian FN and OV
      95% site for physiological high limit were 10 and 9.5 ml respectively. (2) In
      PCOS patients, their ovarian volumes and the number of follicles were
      significantly higher than those of the control group (P < 0.01). (3) In 90.4% of
      these patients, their values were OV > 9.5 ml and/or FN >= 10. And in 66.9% PCOS
      patients of reproductive age, the polycystic ovarian changes of ultrasound
      imaging reached the Rotterdam consensus diagnostic criteria. CONCLUSION: The
      features of ovarian ultrasound imaging in reproductive period PCOS patients are
      enlarged ovarian volume and increased follicles numbers. The preliminary Chinese
      ovarian ultrasonographic diagnostic cut-off points have been proposed for
      reproductive period PCOS patients.

PMID- 23158560
TI  - [Efficacy and safety of low-dose cyclophosphamide plus corticosteroids for type
      I/II myasthenia gravis].
AB  - OBJECTIVE: To evaluate the efficacy and safety of low-dose cyclophosphamide plus
      corticosteroids for type I/II myasthenia gravis (MG). METHODS: This trial was
      prospective, non-random and open-labeled. We selected 160 patients with steroid
      insensitive MG from January 1999 to October 2011. Each patient received an oral
      dose of prednisone 0.5 mg*kg(-1)*d(-1), cyclophosphamide 8 mg*kg(-1)*time(-1)
      once weekly intravenously and oral pyridostigmine 36 mg*kg(-1)*d(-1). The
      efficacies were assessed by absolute and relative MG scores. The clinical
      treatment cycle was 30 weeks. RESULTS: (1) Among them, 74/106 type I MG patients
      (69.9%) reached clinical relative scores >= 95% in 30 weeks. The total dose of
      cyclophosphamide was 12 g. And 35/54 type II MG patients (64.8%) reached clinical
      relative scores >= 95% in 30 weeks. No statistically significant difference
      existed between two groups (P = 0.521). (2) All patients had various degrees of
      improvement in 30 weeks. The difference was statistically significant by Mann
      Whitney U test (P <= 0.05). (3) There were minor side effects in these all
      patients. (4) When the total dose of cyclophosphamide reached 4 g, the cure rate
      in type I patients was higher than that of in type II patients (P = 0.000). When
      the total dose of cyclophosphamide reached 12 g, the cure rate in type II
      patients was higher than that of in type I patients (P = 0.001). (5) The cure
      dose of cyclophosphamide was 4-8 g in 58.4% of type I patients versus 8 - 12 g in
      61.1% of type II patients. CONCLUSION: The combined treatment of low-dose
      cyclophosphamide and corticosteroids in glucocorticoid-insensitive type MG (type
      I/II) is both effective and safe. And the sensitivity to cyclophosphamide varies
      for different clinical types. It is higher in type I than type II patients.

PMID- 23158561
TI  - [Effects of continuous interscalene brachial plexus block plus general anesthesia
      versus general anesthesia alone on perioperative management of arthroscopic
      rotator cuff repair surgery].
AB  - OBJECTIVE: To compare continuous interscalene brachial plexus block (CISB) in the
      patients undergoing rotator cuff repair surgery. METHODS: A total of 60 patients
      undergoing rotator cuff repair surgery were randomly assigned to either ISB plus
      GA group (ISB + GA group) or GA group. Preoperatively, an interscalene catheter
      was placed in the ISB + GA group patients. Both groups received general
      anesthesia. The intraoperative mean arterial pressure (MAP) at the level of
      external acoustic meatus was maintained at a target of 60 - 65 mm Hg with a
      continuous infusion of remifentanil. Postoperatively, the patients in the ISB +
      GA and GA groups received CISB and patient controlled intravenous analgesia
      (PCIA) respectively for 48 h. RESULTS: Surgical field conditions were similar in
      two groups (P = 1.000). Compared to the GA group, the consumption of remifentanil
      [(0.04 +/- 0.03) vs (0.14 +/- 0.03) ug*kg(-1)*min(-1), P < 0.01] and the
      inhalational concentration of sevoflurane(1.80% +/- 0.5% vs 2.1% +/- 0.5%, P <
      0.05)were lower in the ISB + GA group. Compared to the GA group, the values of
      MAP and heart rate (HR) were lower at all postoperative time-points in the ISB +
      GA group(P < 0.05). The postoperative measurements of numerical rating pain score
      (NRPS) were lower (P < 0.01) and the level of patient satisfaction was greater in
      the ISB + GA group [8(6 - 10) vs 7 (5 - 10), P < 0.01]. CONCLUSION: In
      comparisons with GA alone for rotator cuff repair surgery, the combined uses of
      ISB and GA may achieve a better perioperative control of hemodynamic responses, a
      markedly reduced consumption of general anesthetics, a rapid recovery of
      consciousness from anesthesia, superior analgesia with fewer side effects and
      greater patient satisfaction.

PMID- 23158562
TI  - [Bone mineral density and disease activity in untreated systemic lupus
      erythematosus patients].
AB  - OBJECTIVE: To determine the effects of disease activity and other risk factors on
      bone mineral density (BMD) in untreated systemic lupus erythematosus (SLE).
      METHODS: Lumbar and hip BMD were determined by dual energy X-ray absorptiometry
      (DXA) in 50 healthy controls and 120 premenopausal SLE females from Department of
      Rheumatology & Immunology, Third Hospital of Medical College of Jilin University
      during the period of 2010 - 2012. The SLE patients were divided into 2 groups,
      i.e. untreated and treated with glucocorticoid and immunosuppressives. Simple and
      multiple linear regression analyses were performed to determine the associations
      between BMD and disease-related variables. To completely eliminate the influences
      of glucocorticoid treatment on the results, the untreated SLE patients were
      chosen to investigate the risk factors with regression analysis. RESULTS: In
      femoral neck, greater trochanter and total hip, both the treated and untreated
      SLE patients had significantly lower BMD than the healthy controls (P < 0.01). In
      greater trochanter, the treated SLE group had significantly lower BMD than the
      untreated group. The BMD of left and right femoral neck of the former were botj 
      0.06 while that of the later -0.11 and -0.12 respectively (P < 0.05). Regression
      analysis showed that long disease duration and high (SLE disease activity index)
      SLEDAI were the risk factors of low BMD (P < 0.05), especially high SLEDAI.
      CONCLUSION: SLE itself may result in low BMD, especially in patients with high
      SLEDAI. Hip joints are predominantly affected. Long disease duration is also
      closely associated with low BMD in SLE.

PMID- 23158563
TI  - [Predictive factors and unfavorable prognostic factorial analysis of interstitial
      lung disease in patients with inflammatory myopathy].
AB  - OBJECTIVE: To explore the clinical features, predictive factors and unfavourable
      prognostic factors of interstitial lung disease (ILD) in the patients with
      polymyositis and dermatomyositis (PM/DM) so as to provide rationales for early
      clinical diagnosis and treatment. METHODS: The medical records of 244 PM/DM
      patients from Department of Rheumatology & Immunology of Anhui Medical University
      Affiliated Provincial Hospital from August 2001 to August 2011 were reviewed to
      analyze the clinical features, predictive factors and unfavourable prognostic
      factors of ILD in PM/DM patients. RESULTS: The major clinical manifestations of
      PM/DM-ILD included dry cough, chest tightness and shortness of breath during
      activities and Velcro rale in lower lung. Besides anti-Jo-1 antibody,
      multivariate unconditional Logistic regression analysis indicated that amyopathic
      dermatomyositis (ADM), arthralgia/arthritis, fever and Gottron's sign were the
      predictive factors for the development of ILD in PM/DM patients. ADM and Hamman
      Rich-like pattern ILD were the poor prognostic factors while large dose
      glucocorticoids plus immunosuppressant therapy in the early time was a protective
      factor for PM/DM-ILD patients. CONCLUSION: Some clinical features are the
      predictive factors for the development of ILD. ADM and Hamman-Rich-like pattern
      ILD are poor prognostic factors. Large dose glucocorticoids plus
      immunosuppressant therapy can significantly improve the prognosis of PM/DM
      patients.

PMID- 23158564
TI  - [Assessments of total corneal power and intraocular lens power in post-LASIK
      eyes].
AB  - OBJECTIVE: To compare the different evaluations of corneal power in post-laser
      assisted in situ keratomileusis (LASIK) eyes and assess the accuracy and
      differences of intraocular lens (IOL) power prediction with corneal powers
      through different calculation methods. METHODS: For this prospective study, 71
      eyes of 39 candidates undergoing LASIK and 3 months later returning for
      reexamination were included. All subjects were divided into 2 groups according to
      the axial length: Group A (23.46 - 25.97 mm) 44 eyes, Group B (26.00 - 28.52 mm)
      27 eyes. The ranges of spherical equivalents were -1.75 - -9.50 D with an average
      of (-4.82 +/- 1.98) D. Subjective refraction and Pentacam Scheimpflug analyzer
      were performed at pre-operation and subjective refraction, IOLMaster and Galilei
      II dual Scheimpflug analyzer at over 3 months post-operation. The following
      values were obtained: SimK by Galilei II dual Scheimpflug analyzer, Kn calculated
      with Gaussion thick lens formula, Kray with ray tracing method, Kchm calculated
      with clinical history method and Km by IOLMaster. Repeated measures analysis of
      variance analyze the differences between SimK, Kn, Kray, Km and Kchm. Repeated
      measurement analysis of variance was employed to analyze the differences between
      SimK, Kn, Kray, Km combining intraocular lens power formula and Kchm combining
      intraocular lens power formula. Pearson's analysis was performed to analyze the
      correlations between SimK, Kn, Kray, Km and Kchm. Those combining with formulas
      for IOL power calculations were also analyzed. P < 0.05 indicated statistical
      significance. RESULTS: The values of SimK, Kn, Kray, Km and Kchm were (39.02 +/-
      1.8), (37.8 +/- 1.51), (36.8 +/- 1.84), (39.18 +/- 1.75) and (38.55 +/- 1.83) D
      respectively. The differences between SimK, Kn, Kray, Km and Kchm had statistical
      significances (P < 0.01). High correlations existed between SimK, Kn, Kray, Km
      and Kchm (r > 0.9, P < 0.01). In the same IOL formula, Kray had the highest IOL
      power value, Kn followed, Kchm the third, SimK and Km the smallest. Among the IOL
      formulas, Haigis-L and Haigis predicted the highest IOL power, HofferQ followed,
      Holladay the third and SRK/T the smallest. CONCLUSION: Kn/Kray combining with
      Haigis formula may be a new and effective method for predicting the IOL power in
      post-LASIK eyes.

PMID- 23158565
TI  - [Percutaneous achilles tendon lengthening through double hemisection in the
      treatment of achilles contracture syndrome].
AB  - OBJECTIVE: To explore the surgical approach of percutaneous double hemisection
      and evaluate its clinical efficacies. METHODS: From May 2006 to November 2011, a
      total of 59 patients were recruited. There were 36 males and 21 females with a
      mean age of 38.2 years (range: 8 - 62). Forty-two varus and 6 valgus feet
      underwent percutaneous double hemisection. The 0.5 cm coracoid incision was
      adopted at the medial and lateral aspects of Achilles tendon. Percutaneous double
      hemisection was employed according to the deformity angles of varus and valgus
      feet. Manipulative correction was applied slowly until 30 degrees  dorsiflexion
      of ankle. Short leg cast was immobilized for 5 weeks at 30 degrees  dorsiflexion
      of ankle. The force of Achilles tendon, motion of ankle and Hannover Achilles
      tendon scores were followed up. RESULTS: Fifty-two patients were followed up for
      a mean period of 16.5 months (range: 6 - 60). Seven patients were lost. At the
      end of follow-up, 48 patients with varus and valgus deformities were corrected
      effectively. When compared with the normal side, the force of Achilles of the
      operated side of 50 patients had no change while that of 2 patients decreased
      slightly; the motion of ankle joint increased from (2.8 +/- 0.3) degrees 
      preoperatively to (28.5 +/- 1.4) degrees  postoperatively (P < 0.05); the
      Hannover Achilles Tendon Scores rose from (68.5 +/- 3.5) preoperatively to (82.6
      +/- 4.2) points postoperatively (P < 0.05). The outcomes were excellent (n = 44),
      very good (n = 5), good (n = 2) and poor (n = 1). The excellent and good rate was
      94.2%. CONCLUSION: As an effective therapy for Achilles tendon contracture
      syndrome, percutaneous double hemisection has fewer complications and a faster
      recovery.

PMID- 23158566
TI  - [The study in detection of microcalcification in early breast cancer by
      ultrasound and its correlation with pathohistology].
AB  - OBJECTIVE: To discuss the role of ultrasound in examining microcalcification of
      early breast cancer and its correlation with pathohistological type and grade.
      METHODS: 178 lesions in 165 cases of early breast cancer confirmed by pathology
      after surgical resection were examine by high frequency ultrasound, meanwhile
      microcalcification were detected and reported. 39 lesions in 32 cases are
      carcinoma in situ and microinvasive carcinoma of breast. 139 lesions in 133 cases
      are early invasive breast carcinoma that is below 2 cm in diameter and doesn't
      invasive the lymph node and other parts of the body. To analyse the sensitivity
      of detection micro-calcification of early breast cancer by ultrasound and its
      correlation with pathohistological type and grade. RESULTS: The sensitivity is
      81.6% in detecting microcalcification of early breast cancer by ultrasound. There
      is no significant statistical difference in detecting microcalcification between
      the two group (P = 0.217). There is no significant statistical difference in
      detecting microcalcification of early invasive breast cancer between the
      different pathologic types (P > 0.05), and there are no significant differences
      in detecting microcalcification of early breast cancer between the different
      pathologic grades (group I: P = 0.202, group II: P = 0.415). There is significant
      difference in detecting microcalcification of solid tumor by ultrasonic
      examination in group I between the different pathologic grades (P = 0.029).
      CONCLUSION: There is higher sensitivity in detecting microcalcification of early
      breast cancer by ultrasonography. Microcalcification of early breast cancer may
      be no closely related to pathologic grades. US has a certain value to clinic in
      detecting microcalcification of early breast cancer.

PMID- 23158567
TI  - [Alternation of proteins in brain of Parkinson's disease model rats after the
      transplantation of TH-NTN gene modified bone marrow mesenchymal stem cells].
AB  - OBJECTIVE: To explore the effects of tyrosine hydroxylase-neurturin (TH-NTN) gene
      modified bone marrow mesenchymal stem cell (BMSC) transplantation in Parkinson's
      disease (PD) model rats and the alternations of correlated proteins. METHODS: The
      PD rat model was established by the 2-point injection of 6-hydroxydopamine (6
      OHDA) into unilateral (right) striatum. Successful modeling rats were separated
      into PD, BMSC and TH-NTN-BMSC groups. BMSC and TH-NTN-BMSC groups were
      transplanted into BMSCs and TH-NTN gene modified BMSC cells separately into right
      striatum. After transplantation, ethology detection in all groups was made with
      an intraperitoneal injection of apomorphine (APO). Dopamine (DA) and
      Dihydroxyphenylacetic Acid (DOPAC) in striatum were detected by high performance
      liquid electrochemical analysis. TH and NTN proteins in right striatum were also
      analyzed by immunohistochemistry and Western blot. Finally the density of
      dopamine receptors in post synaptic density of dopaminergic synapses of corpus
      striatum were compared between each group by post-embedding immunogold electron
      microscopy. RESULTS: After an injection of APO, rotation frequency decreased in
      TH-NTN-BMSC group, i.e. (5.7 +/- 1.3) circles/min versus (10.8 +/- 2.2), (9.9 +/-
      1.2) circles/min in PD and BMSC groups (P < 0.05). For proteins in right
      striatum, DA, (0.421 +/- 0.113) and DOPAC, (0.093 +/- 0.012) nmol/L increased
      significantly versus (0.208 +/- 0.043), (0.043 +/- 0.017) nmol/L in PD and (0.231
      +/- 0.082), (0.044 +/- 0.023)noml/L in BMSC groups (P < 0.05). Also a lower
      density of D2 receptors at (623 +/- 96)/um(2) in TH-NTN-BMSC group versus (923 +/
      132)/um(2) in PD and (860 +/- 116)/um(2) in BMSC groups was also found.
      CONCLUSION: The combined therapy of TH and NTN genes increases the synthesis of
      DA and also protects the dopaminergic neurons to achieve double therapeutic
      effects. It may provide potential innovations of PD genetic therapy.

PMID- 23158568
TI  - [Damage of blood brain barrier of spinal cord in rats with chronic fluorosis].
AB  - OBJECTIVE: To explore the impairment mechanisms of blood brain barrier in spinal
      cord and observe the changes of matrix metalloproteinase-9 (MMP-9) and functional
      improvement in rats with chronic fluorosis. METHODS: A total of 120 Wistar rats
      were divided randomly into 4 groups, high fluoride (fed by water with a high
      concentration of sodium fluoride at 200 mg/L), high fluoride control (fed by
      distilled water), defluorination (fed by water with a high concentration of
      sodium fluoride at 200 mg/L for 12 weeks and then distilled water for 12 weeks)
      and defluorination control (n = 30 each). The urinary contents of fluoride were
      detect for 4 groups at Weeks 4, 8 and 12. The high fluoride and control groups
      were sacrificed at Week 12 while the defluorination and defluorination control
      groups at Week 24. Their cervical spinal cords were collected for electron
      microscope examinations. The expression of MMP-9 protein in thoracic cord was
      detected by immunohistochemistry and Western blot. Quantitative analysis of
      function of blood brain cord barrier was performed by the technique of Evans
      blue. The comparison of measurement data was performed with F test and
      correlation analysis. The cytological changes of neurons in thoracic spinal cord
      were detected after chronic fluorosis. RESULTS: Under electron microscope, the
      pathological manifestations of chronic damage in blood brain barrier could be
      found. As compared with the high fluoride control group, the content of Evans
      blue increased markedly in spinal cord of the high fluoride group (29.2 +/- 0.1
      vs 0.7 +/- 0.1 mg/L, P < 0.01). It was higher in the defluorination group than
      that in the defluorination control group. But there was no significant difference
      with the high fluoride group (29.2 +/- 0.1 vs 28.9 +/- 0.2 mg/L, P > 0.01). And
      the expression of MMP-9 increased in spinal cord of the fluorosis and
      defluorination groups in comparison with those in the control group. But no
      difference existed among them. CONCLUSION: The damage of blood brain barrier of
      spinal cord occurs probably as a result of a higher expression of MMP-9 in rats
      with chronic fluorosis. Defluorination for a short time may not recover.

PMID- 23158569
TI  - [Effects of pretreatment of lipid, midazolam and propofol on ropivacaine-induced
      convulsion and LD50 in rats].
AB  - OBJECTIVE: To assess the effects of lipid on ropivacaine-induced convulsion and
      LD50 in rats and compare with those of the traditional anticonvulsants midazolam
      and propofol. METHODS: Protocol 1: A total of 120 SD rats (60 males, 60 females),
      weighing 200-300 g, were randomly assigned into 4 groups with equal males and
      females: lipid (L), midazolam (M) and propofol (P) and control (C). Rats were
      pretreated with 10 ml/kg lipid intravenously in group L, saline and 0.23 mg/kg
      midazolam (10 ml/kg in volume) sequentially in group M, saline and 4 mg/kg
      propofol (10 ml/kg in volume) in group P and saline 10 ml/kg in group C. Then
      ropivacaine 44 mg/kg (0.75%) was injected intraperitoneally into each rat. The
      convulsion rate in each group and the time of convulsion after ropivacaine
      injection were observed. Meanwhile, the plasma concentration of ropivacaine at
      the time of convulsion was measured. Protocol 2: Additional 100 male SD rats were
      used for the measurements of ropivacaine LD50 with different pretreatments
      including lipid, midazolam, propofol and saline through the up-and-down method.
      Rats were randomly assigned into 4 groups similarly as protocol 1. The doses of
      ropivacaine in each group were determined according to our pilot study and 6
      dosage levels with the same interval ratio 8.5 was applied in each group. The
      doses of these pretreatment drugs and administration methods were similarly as
      protocol 1. RESULTS: The convulsion rate after 44 mg/kg ropivacaine ip injection
      was 43.3% in group C, 0% in group M, 13.3% in group P and 70% in group L. Lipid
      increased the convulsion rate significantly. The plasma concentration of
      ropivacaine at the time of convulsion was 1.65 +/- 0.30 ug/kg in group C, 1.73 +/
      0.14 ug/kg in group P and 3.45 +/- 0.26 ug/kg in group L. The LD50 of
      ropivacaine in group C was 64.39 mg/kg, 88.40 mg/kg in group M and 90.20 mg/kg in
      group P and 55.45 mg/kg in group L. CONCLUSIONS: Midazolam and propofol not only
      decrease the convulsion rate of ropivacaine, but also increase its LD50. Lipid
      not only increases the convulsion rate of ropivacaine, but also decreases its
      LD50. The application of lipid for the prevention of local anesthetic toxicity
      has potential risks.

PMID- 23158570
TI  - [Intranasal dosing of nerve growth factor protects brain from poisoning of
      organophosphorus compounds in rats].
AB  - OBJECTIVE: To explore the protective effects of intranasal (IN) dosing of nerve
      growth factor (NGF) on brain injury induced by organophosphorus compounds (OP) in
      rats. METHODS: The OP-treated Sprague-Dawley rats received an intraperitoneal
      injection of atropine sulphate and pralidoxime at 1 min after intoxication. Then
      NGF or saline was dosed via the olfactory pathway. All rats were sacrificed 24
      hours after OP exposure. Damaged nerve cells were estimated on corpus striatum
      strained with hematoxylin-eosin (H&E) method. And the activity of
      acetylcholinesterase (AchE) and the concentrations of malondialdehyde (MDA) and
      reduced glutathione hormone (GSH) in corpus striatum were measured by
      colorimetric method. RESULTS: As assessed by H&E staining, a large number of
      degenerated and necrotic nerve cells were observed in corpus striatum in rats
      from in IN saline group. But in IN NGF group, the number of degenerated neurons
      was smaller than in IN NS group. Following OP exposure, the activity of AchE
      decreased in corpus striatum in both IN saline and IN NGF groups (0.46 +/- 0.11
      vs 0.35 +/- 0.09 U/mg prot). No significant differences existed between two
      groups. But the concentrations of MDA in corpus striatum of IN NGF group rats
      reduced markedly by 25.14% (4.02 +/- 0.85 vs 5.37 +/- 1.33 nmol/mg prot) and the
      level of GSH increased sharply by 15.73% (52.82 +/- 2.80 vs 45.64 +/- 4.88 mg/g
      prot) as compared with IN saline group (P < 0.05). CONCLUSION: Intranasal dosing
      of NGF may improve neuropathology and protect rats against OP-induced oxidative
      damage in corpus striatum.

PMID- 23158571
TI  - Decitabine induces very early in vivo DNA methylation changes in blasts from
      patients with acute myeloid leukemia.
AB  - In vivo effects of the DNA hypomethylating agent 5-aza-2'-deoxycytidine (DAC)
      upon the epigenome of acute myeloid leukemia (AML) patients are scarcely studied
      in primary blasts. Here, we sequentially assessed DNA methylation and
      transcriptome changes in myeloblasts of DAC-treated AML patients. DNA methylation
      changes were detected in all patients already after the first series of infusion
      (median: 6 days). LINE1 analysis indicated global DNA methylation decrease in 7/8
      patients. Gene-specific hypomethylating effects were not directly linked to mRNA
      expression changes. In conclusion, complex DAC-induced DNA methylation changes
      occur very early and imply mechanisms distinct from non-hypomethylating cytosine
      analogs.

PMID- 23158572
TI  - The role of answer fluency and perceptual fluency as metacognitive cues for
      initiating analytic thinking.
AB  - Although widely studied in other domains, relatively little is known about the
      metacognitive processes that monitor and control behaviour during reasoning and
      decision-making. In this paper, we examined the conditions under which two
      fluency cues are used to monitor initial reasoning: answer fluency, or the speed
      with which the initial, intuitive answer is produced (Thompson, Prowse Turner, &
      Pennycook, 2011), and perceptual fluency, or the ease with which problems can be
      read (Alter, Oppenheimer, Epley, & Eyre, 2007). The first two experiments
      demonstrated that answer fluency reliably predicted Feeling of Rightness (FOR)
      judgments to conditional inferences and base rate problems, which subsequently
      predicted the amount of deliberate processing as measured by thinking time and
      answer changes; answer fluency also predicted retrospective confidence judgments
      (Experiment 3b). Moreover, the effect of answer fluency on reasoning was
      independent from the effect of perceptual fluency, establishing that these are
      empirically independent constructs. In five experiments with a variety of
      reasoning problems similar to those of Alter et al. (2007), we found no effect of
      perceptual fluency on FOR, retrospective confidence or accuracy; however, we did
      observe that participants spent more time thinking about hard to read stimuli,
      although this additional time did not result in answer changes. In our final two
      experiments, we found that perceptual disfluency increased accuracy on the CRT
      (Frederick, 2005), but only amongst participants of high cognitive ability. As
      Alter et al.'s samples were gathered from prestigious universities, collectively,
      the data to this point suggest that perceptual fluency prompts additional
      processing in general, but this processing may results in higher accuracy only
      for the most cognitively able.

PMID- 23158573
TI  - Acute cyanide intoxication due to apricot seed ingestion.

PMID- 23158574
TI  - A simple mnemonic for the acute and continued medical treatment of ST-elevation
      myocardial infarctions.

PMID- 23158575
TI  - "Air bubble" in the head after transanal excision of a rectal carcinoma.

PMID- 23158577
TI  - Toward the connectomic era.

PMID- 23158576
TI  - Palliation of abdominal aortic aneurysms in the endovascular era.
AB  - OBJECTIVES: To establish outcome of patients with abdominal aortic aneurysm (AAA)
      deemed unfit for repair. DESIGN: Retrospective non-randomised study. MATERIALS
      AND METHODS: Identification of males with >5.5 cm or females with >5.0 cm AAA
      turned down for elective repair between 01/01/2006-24/07/2009 from a prospective
      database. Comorbidities, reasons for non-intervention, aneurysm size, survival,
      use of CPEX (cardio-pulmonary exercise) testing and cause of death were analysed.
      Although well-established at the time, patients unfit for open operation were not
      considered for endovascular repair. RESULTS: Seventy two patients were unsuitable
      for AAA repair. Aneurysm size ranged from 5.3 cm to 12 cm. Functional status,
      comorbidity and patient preference determined decision to palliate. Sixty percent
      of patients were alive at study close. Aneurysm rupture was cause of death in
      46%. CPEX testing was performed in 54%, whose mortality was 28%, vs. 54% in the
      non-CPEX group (P < 0.05). Median survival of patients with 5.1-6.0 cm AAA was 44
      months and 11% died of rupture. Between 6.1 and 7.0 cm median survival was 26
      months and 20% died of rupture. However, with >7 cm aneurysms, survival was 6
      months and 43% ruptured. CONCLUSION: Under half the deaths in our comorbid cohort
      were due to rupture. However, decision to palliate may be revisited as risk
      benefit ratio changes with aneurysm expansion.

PMID- 23158578
TI  - The prognostic value of motor-evoked potentials in motor recovery and functional
      outcome after stroke - a systematic review of the literature.
AB  - The aim of this study was to systematically review published data on the value of
      motor-evoked potentials (MEPs) in predicting motor recovery of the upper
      extremity and general functional outcome early after stroke. We searched PubMed
      for original prognostic studies. Only full-text original papers evaluating the
      prognostic value of MEPs elicited by transcranial magnetic stimulation (TMS) in
      motor function recovery of the upper extremity were included in this review. Data
      from the studies included in the review are presented in two tables: one shows
      the general characteristics of the studies and the other gives methodological
      details and results. Of 842 publications, only 15 met the criteria for inclusion
      in this review. Data from 14 trials provided evidence that TMS of the motor
      cortex, eliciting MEPs, is a reliable tool for predicting motor recovery as well
      as functional outcome. The interpretation of the results was complicated by
      methodological differences between the included studies.

PMID- 23158579
TI  - A new approach to structural integrity assessment based on axial and radial
      diffusivities.
AB  - This study describes a method for performing diffusivity measures along and
      across a specific direction, derived from white matter in healthy controls. The
      diffusion tensor (DT) assigns a principal eigenvector (v1) and eigenvalue (axial
      diffusivity, d(ax)) to each voxel. The average of the second and third
      eigenvalues is the radial diffusivity, d(rad) v1 may be affected by pathology,
      therefore when comparing d(ax) and d(rad) in patients one has to consider the
      direction of the measurement and underlying anatomy. Here we created a
      representative super-DT dataset, DT(ref), whose eigenvector, v(1,ref), was
      considered the most likely direction of diffusivity per voxel. We defined the
      projected axial diffusivity, d(p-ax), as the projection of individual DTs along
      v(1,ref) and the projected radial diffusivity, d(p-rad), as the average of the
      projections along the second and third eigenvectors of DT(ref). The projected
      diffusivities are promising new parameters for studying white matter pathology.

PMID- 23158580
TI  - Evidence of increased restless legs syndrome occurrence in chronic and highly
      disabling migraine.
AB  - The existence of an association between migraine and restless legs syndrome (RLS)
      has recently been reported, although the possible implications of this for
      migraine clinical presentation remain poorly understood. The objectives of this
      study were to determine RLS frequency in a population of migraineurs compared
      with healthy subjects and to assess RLS occurrence in episodic versus chronic
      migraine patients; the relationship between migraine-related disability and RLS
      comorbidity was also evaluated. Two hundred and seventy-seven consecutive
      migraineurs (ICHD-II, 2004) were enrolled and compared with 200 controls;
      migraine was episodic in 175 and chronic in 102 patients. RLS (IRLSSG criteria,
      2003) was present in 22.7% of the total sample of migraineurs and in 7.5% of the
      controls (p<0.0001). RLS occurred significantly more frequently in chronic
      compared with episodic migraineurs (34.3% vs 16%, respectively, p=0.0006); a
      significant association between RLS diagnosis and moderate-severe migraine
      related disability was also documented (p=0.0003). In conclusion, the results of
      the present study not only confirm the higher occurrence of RLS in migraine
      patients compared with the general population, but also suggest that RLS (the
      condition itself, or the disruption of sleep patterns often found in patients
      affected by RLS) might affect migraine clinical presentation, being associated
      with chronic and highly disabling migraine. These findings could have important
      therapeutic and prognostic implications in clinical practice.

PMID- 23158581
TI  - Depressive symptoms among surrogate decision makers in Lebanese ICUs.
AB  - Surrogate decision making is advocated to protect the vulnerable patient. Family
      members of patients in intensive care units (ICUs) are prone to develop
      depressive symptoms which may undermine their decisional capacity. Lebanon is a
      multicultural country where paternalism still dominates the physician-patient
      relationship and ethics are far from being the subject of research and studies.
      This multicenter observational study in the Greater Beirut area attempts to
      estimate the prevalence of depressive symptoms among surrogates deciding on
      behalf of ICU patients and to correlate their severity with sociodemographic
      factors. During the period March-May 2011, direct interviews were conducted and
      the Patient Health Questionnaire-9 (PHQ-9) was administered to 56 family members
      who had given consent, regarding therapeutic options, on behalf of ICU patients
      in seven university hospitals. We looked for relationships, in these surrogates,
      between severity of depression and age, sex, marital status, level of education,
      religion and status as the patient's spouse. The prevalence of major depression
      among surrogates was 61% using a cutoff of 10 on the PHQ-9 scale. Among the
      surrogates with depression, 15% had untreated moderate-to-severe depression.
      Severity of depression and suicidal ideation were not related to any of the
      studied factors. Depressive symptoms are prevalent among family members deciding
      on behalf of ICU patients, rendering them vulnerable. Appropriate measures should
      be taken to identify and treat them.

PMID- 23158582
TI  - Mortality and prognosis in patients with neurogenic orthostatic hypotension.
AB  - The prognosis of neurogenic orthostatic hypotension (NOH) has been poorly
      studied. The aim of this study was to evaluate retrospectively comorbidities and
      causes of death in patients with NOH. Clinical information and causes of death
      were obtained for 104 patients (45 with multiple system atrophy, 9 with pure
      autonomic failure, 43 with Parkinson's disease, and 7 with other types of
      autonomic neuropathy) referred to the Autonomic Unit from 1996 to 2009.
      Cardiovascular diseases (hypertension, cardiac comorbidities, atrial fibrillation
      and heart failure) were present in 53 (51%) NOH patients. At the end of follow
      up, 44 patients were deceased. Type of NOH was the main factor associated with
      mortality. The main causes of death were infectious/respiratory (54%) and cardiac
      (16%). In NOH patients, cardiovascular diseases are frequent, although mortality
      is mainly due to infectious and respiratory causes. Detection of cardiovascular
      diseases may be useful in the choice of anti-hypotensive treatments.

PMID- 23158584
TI  - A case for full spinal screening in trauma patients without obvious clinical
      signs.

PMID- 23158583
TI  - Lombardia GENS: a collaborative registry for monogenic diseases associated with
      stroke.
AB  - The Italian region of Lombardy, with its existing stroke centers and high
      technology laboratories, provides a favorable context for studying monogenic
      diseases associated with stroke. The Lombardia GENS project was set up to create
      a regional network for the diagnosis of six monogenic diseases associated with
      stroke: CADASIL, Fabry disease, MELAS, familial and sporadic hemiplegic migraine,
      hereditary cerebral amyloid angiopathy and Marfan syndrome. The network comprises
      36 stroke centers and seven high-technology laboratories, performing molecular
      analysis. In this context, all stroke/TIA patients fulfilling clinical criteria
      for monogenic diseases are currently being included in an ongoing study.
      Demographic, clinical and family data and diagnostic criteria are collected using
      standardized forms. On the basis of stroke incidence in Lombardy and the reported
      prevalence of the diseases considered, we expect, during the course of the study,
      to collect datasets and DNA samples from more than 200 stroke patients suspected
      of having monogenic diseases. This will allow evaluation of the regional burden
      and better phenotype characterization of monogenic diseases associated with
      stroke.

PMID- 23158585
TI  - Selenium (sodium selenite) causes cytotoxicity and apoptotic mediated cell death
      in PLHC-1 fish cell line through DNA and mitochondrial membrane potential damage.
AB  - Elevated concentration of selenium poses a toxic threat to organisms inhabiting
      aquatic ecosystems influenced by excessive inputs from anthropogenic sources.
      Selenium is also an essential micronutrient in living things, particularly in
      fish, and provides antioxidant properties to tissues. Whole fish and hepatocytes
      in primary culture show selenite toxicity above threshold levels. The present
      study was designed to investigate the process by which selenite exposure causes
      cellular toxicity and apoptotic and necrotic cell death in fish hepatoma cell
      line PLHC-1. PLHC-1 cells were exposed to various selenite concentrations (1, 10,
      50 and 100 MUM) for 10, 20 and 40 h intervals. The 24h inhibitory concentration
      50 (IC50) of selenite in PLHC-1 cell line was found to be 237 MUM. Flow
      cytometery data showed that selenite exposed cells promote apoptotic and necrotic
      mediated cell death when selenite concentrations were >=10 MUM compared to
      control. Selenite exposure was associated with a significant increase of caspase
      3 activities suggesting the induction of apoptosis. Selenite exposure at high
      levels (>=10 MUM) and longer exposure times (>=20 h) induces mitochondrial
      membrane potential damage (DeltaPsi(m)), DNA damage and elevated production of
      ROS which could be associated with cell death.

PMID- 23158587
TI  - Reply to Chandra Shekhar Biyani, Andy Myatt, Victor Palit, Neil Burgess and
      Adrian D. Joyce's letter to the editor re: Jean J.M.C.H. de la Rosette, Dedan
      Opondo, Francisco P.J. Daels, et al., on behalf of the CROES PCNL Study Group.
      Categorisation of complications and validation of the clavien score for
      percutaneous nephrolithotomy. Eur Urol 2012;62:246-55.

PMID- 23158586
TI  - A phenotypic screening platform to identify small molecule modulators of
      Chlamydomonas reinhardtii growth, motility and photosynthesis.
AB  - Chemical biology, the interfacial discipline of using small molecules as probes
      to investigate biology, is a powerful approach of developing specific, rapidly
      acting tools that can be applied across organisms. The single-celled alga
      Chlamydomonas reinhardtii is an excellent model system because of its
      photosynthetic ability, cilia-related motility and simple genetics. We report the
      results of an automated fitness screen of 5,445 small molecules and subsequent
      assays on motility/phototaxis and photosynthesis. Cheminformatic analysis
      revealed active core structures and was used to construct a naive Bayes model
      that successfully predicts algal bioactive compounds. 

PMID- 23158588
TI  - Surgical benign prostatic hyperplasia trials: the future is now!

PMID- 23158589
TI  - Minimally invasive postchemotherapy retroperitoneal lymph node dissection:
      caution and prudence.

PMID- 23158590
TI  - Tadalafil for the treatment of benign prostatic hyperplasia: when the moment does
      not add up.

PMID- 23158591
TI  - A novel, nonoperative treatment for delayed penile zipper injury.

PMID- 23158592
TI  - Comparison of 2 cuff inflation methods before insertion of laryngeal mask airway
      for safe use without cuff manometer in children.
AB  - PURPOSE: This prospective, randomized trial was conducted to establish whether
      the pediatric laryngeal mask airway (LMA) could be used without any concerns for
      abnormally high intra-cuff pressure when a cuff of the LMA was inflated with half
      the maximum recommended inflation volume or the resting volume before insertion.
      BASIC PROCEDURES: Eighty children 0 to 9 years of age and weighing of 5 to 30 kg
      scheduled for general anesthesia were included. Before insertion, the cuff of the
      LMA was filled with half the maximum recommended inflation volume in the Half
      volume group, or the resting volume by opening the pilot balloon valve to
      atmospheric pressure in the Resting volume group. After insertion of the LMA,
      intra-cuff pressure, oropharyngeal leak pressure, and leakage volume were
      investigated. MAJOR FINDINGS: The Half volume group showed lower mean intra-cuff
      pressure than the Resting volume group (49.6 +/- 12.1 cm H(2)O vs 58.1 +/- 13.8
      cm H(2)O, P = .005). There was no difference in oropharyngeal leak pressure (22.1
      +/- 5.8 vs 21.7 +/- 5.1 cm H(2)O, P = .757) or leakage volume between the Half
      volume group and the Resting volume group (0.13 +/- 0.13 ml/kg vs 0.11 +/- 0.12
      ml/kg, P = .494) under spontaneous respiration. CONCLUSIONS: Both methods of the
      LMA cuff inflation before insertion provided an acceptable range of intra-cuff
      pressure with adequate pharyngeal sealing without any intervention after
      insertion.

PMID- 23158593
TI  - Necrotizing soft tissue infection with gas formation caused by Vibrio vulnificus
      and misdiagnosed as Pseudomonas aeruginosa.

PMID- 23158594
TI  - Comparison between journals from mainland China and international journals in the
      field of emergency medicine.

PMID- 23158595
TI  - Comparison of 3 video laryngoscopes with the Macintosh in a manikin with easy and
      difficult simulated airways.
AB  - OBJECTIVES: Tracheal intubation is used to maintain a patent airway and can
      occasionally be difficult in a potentially difficult airway, especially for
      novice managers. In this study, we evaluated the time required, extent of the
      difficulty, and number of dental clicks in the tracheal intubation for novice
      medical students between the Macintosh (Truphatek International Ltd, Netanya,
      Israel) and 3 video laryngoscopes in normal and difficult simulated intubation
      positions on manikins on both the table and floor. METHODS: We recruited 20
      medical students as novice airway managers. They used the Macintosh, Truview
      (Truphatek International Ltd, Netanya, Israel), Glidescope (Verathon Inc.,
      Bothell, WA), and Airway Scope (AWS) (Pentax Corporation, Tokyo, Japan)
      laryngoscopes in normal and difficult simulated airways on manikins on both the
      table and floor. The time to intubate, modified Cormack-Lehane score, intubation
      difficulty score, and dental click number were estimated and compared. RESULTS:
      All 20 medical students completed the study. The AWS required the shortest
      intubation time, provided the best glottic view and easiest intubation, and
      resulted in less dental clicks compared with the other 3 laryngoscopes; these
      phenomena were particularly prominent in the cervical-spine immobilization
      position on the floor. Although all video laryngoscopes provided better glottic
      views than the Macintosh laryngoscopy in terms of time to intubate, intubation
      difficulty score, and the number of dental clicks, the outcomes from the
      Macintosh laryngoscope were better than those of the Truview and Glidescope.
      CONCLUSIONS: The AWS may have the potential for quicker, easier, and safer
      tracheal intubation in scenarios involving difficult airways for a novice airway
      manager.

PMID- 23158596
TI  - Diagnosing anterior shoulder dislocation in the not-so-slim and obese: a novel
      examination technique.

PMID- 23158597
TI  - Epidemiology of injuries to wildland firefighters.
AB  - INTRODUCTION: Wildland fires have significant ecologic and economic impact in the
      United States. Despite the number of firefighters involved in controlling them,
      little is known about the injuries that they sustain. We hypothesized that the
      mechanism of injury would predict injury characteristics and severity of fire
      related injuries. METHODS: We examined firefighter injuries reported to the US
      Department of the Interior from the years 2003 to 2007. Associations between the
      injury mechanism and the injury diagnosis and body part were assessed. A logistic
      regression model was used to evaluate the odds of disabling injury associated
      with mechanism of injury after controlling for demographic and temporal
      variables. RESULTS: A total of 1301 nonfatal injuries to wildland firefighters
      were reported during the 5-year period. Mechanism of injury was significantly
      associated with the type of injury and injured body part (P <= .001). The most
      common injury mechanism was slips/trips/falls followed by
      equipment/tools/machinery. Injuries from poisoning or environmental exposure were
      less likely to lead to severe injury than slips, trips, or falls (odds ratio,
      0.45; 95% confidence interval, 0.21-0.95). Compared with injuries in the early
      and peak season, those in the late season had more than twice the odds of being
      severe (odds ratio, 2.24; 95% confidence interval, 1.23-4.10). DISCUSSION: This
      study contributes important knowledge for implementing evidence-based injury
      prevention programs, for planning emergency medical responses on fire incidents
      and for provoking further inquiry into occupational risk factors affecting this
      high-risk occupational group.

PMID- 23158598
TI  - Mysterious neck pain.

PMID- 23158599
TI  - Nontraumatic unilateral proptosis.

PMID- 23158600
TI  - The role of autonomic nervous system function in hypothermia-mediated sepsis
      protection.
AB  - OBJECTIVE: The objective of this study is to determine whether hypothermia will
      lessen decreases in heart rate variability and improve outcome in a rat model of
      sepsis. METHODS: Thirty-six male Sprague-Dawley rats were randomized into 3
      groups: control, low sepsis, and high sepsis groups. These groups were each
      subdivided into a normothermia (37 degrees C) (n = 6) and a hypothermia group (34
      degrees C) (n = 6). Cyclophosphamide (100 mg/kg) was administered 5 days before
      Staphylococcus aureus injection to produce conditions in which sepsis could be
      induced reliably. Hypothermic rats received temperature reduction for 1 hour post
      injection. Electrocardiogram was recorded before, after, and 1 day after
      staphylococcal injection, and the low frequency, high frequency (HF), and LF/HF
      ratio measurements of heart rate variability and the frequencies of arrhythmia
      were recorded. The effects of time, sepsis severity, and hypothermia on these
      variables were analyzed using a multivariate generalized estimation equation
      mode. RESULTS: Four deaths occurred in the normothermic group, and none, in the
      hypothermic group. Sepsis of both low and high severity increased low frequency
      and HF 1 day after sepsis induction. Hypothermia significantly decreased HF in
      low, but not high sepsis severity. CONCLUSIONS: Hypothermia decreased mortality
      in septic rats. The influence of hypothermia on HF depended on the severity of
      the sepsis.

PMID- 23158601
TI  - Brain infarction after dissection of the intrathoracic arteries secondary to
      acute epiglottitis.

PMID- 23158602
TI  - Extracorporeal membrane oxygenation support as bridge to recovery in a patient
      with electrical storm related cardiogenic shock.

PMID- 23158603
TI  - Identifying patients with cellulitis who are likely to require inpatient
      admission after a stay in an ED observation unit.
AB  - BACKGROUND: Emergency department observation units (EDOU) are often used for
      patients with cellulitis to provide intravenous antibiotics followed by a
      transition to an oral regimen for discharge. Because institutional regulations
      typically limit EDOU stays to 24 hours, patients lacking a clinical response
      within this period will often be subsequently admitted to the hospital for
      further treatment. OBJECTIVE: The aim of this study was to determine the rate of
      hospital admission and characteristics predictive of admission in patients with
      cellulitis who are initially placed in an ED observation unit. METHODS: A
      retrospective cohort study of patients placed into EDOU with a diagnosis of skin
      infection was conducted. Age, sex, history of diabetes mellitus,
      immunosuppression, intravenous drug use, location of cellulitis, presence of
      abscess, laboratory infectious markers, vital signs, and outpatient antibiotic
      treatment were recorded. The primary outcome was a hospital admission due to
      failure to respond to treatment within the 24-hour observation time window.
      Significant variables on univariate analysis were used to create a multivariate
      analysis, which identified predictive characteristics. RESULTS: Four hundred six
      patient charts were reviewed, with 377 meeting inclusion criteria; the inpatient
      admission rate from EDOU was 29.2%. Using logistic regression techniques, we
      created a model of independent predictors for need of admission after 24 hours:
      cellulitis of the hand (odds ratio [OR], 2.9; 95% confidence interval [CI], 1.8
      4.9), measured temperature higher than 100.4 degrees F (OR, 2.5; 95% CI, 1.1
      5.5), and lactate greater than 2 (OR, 3.1; 95% CI, 1.3-7.3) were predictive of
      failure of ED observation. CONCLUSIONS: Patients with cellulitis placed into ED
      observation status were more likely to fail an observation trial if they had an
      objective fever in the ED, an elevated lactate, or a cellulitis that involved the
      hand.

PMID- 23158604
TI  - Correlation between capillary and arterial blood gas parameters in an ED.
AB  - BACKGROUND AND AIMS: Sampling from arteries for the analysis of blood gases is a
      common procedure in emergency departments (ED). The procedure is painful for the
      patients and causes concern for the medical personnel due to possible
      complications, such as hematoma, infection, ischemia, and formation of fistula or
      aneurism. The present study compared the results of capillary and arterial blood
      gases analyses (CBG and ABG) to emphasizing a less aggressive technique with the
      fewest complications for this procedure. MATERIALS AND METHODS: In the
      comparative/analytical study, the results of ABG and CBG for 187 patients
      referring to the ED of a teaching hospital were compared using SPSS 18
      statistical software (SPSS, Chicago, IL) in relation to the mean partial pressure
      of oxygen (Po(2)), partial pressure of carbon dioxide (Pco(2)), base excess (BE),
      bicarbonate (HCO(3)), serum acidity (pH), and saturation of hemoglobin oxygen
      (SaO(2)). RESULTS: Saturation of hemoglobin oxygen, HCO(3), pH, Pco(2), Po(2),
      and BE exhibited significant statistical correlation between ABG and CBG (P =
      .001). The average correlations between capillary and arterial samples were 0.78
      for pH, 0.73 for Pco(2), 0.71 for BE, 0.90 for HCO(3), 0.77 for Po(2), and 0.52
      for SaO(2). Comparison of the parameters means did not exhibit significant
      differences between arterial and capillary samples except for Po(2) and SaO(2) (P
      > .05). CONCLUSION: There appear to be strong correlation between samples
      collected from the finger tip capillaries with the arterial blood samples in
      relation to the analysis of blood gas.

PMID- 23158605
TI  - Sonographic evidence of spontaneous pneumomediastinum.

PMID- 23158606
TI  - Diamine oxidase in diagnosis of acute mesenteric ischemia.
AB  - OBJECTIVE: Acute mesenteric ischemia (AMI) is an important clinical condition
      with a high mortality rate in abdominal emergencies due to delay in diagnosis in
      spite of the new strategies in the management. We have studied the role of
      diamine oxidase (DAO) in the early diagnosis of AMI. METHODS: In the study, 21
      New Zeland rabbits were used. Subjects were named as the groups of controls,
      sham, and ischemia. No intervention was performed in the subjects in the control
      group. In the subjects from sham and ischemia groups, laparotomy was performed
      with middle line incision. However, superior mesenteric artery was found and tied
      in those from ischemia group after the performance of laparotomy. From the
      animals in 3 groups, blood was drawn at the hours of 0, 1, 3, and 6, and DAO and
      amylase were studied in these samples. RESULTS: The increase in serum amylase
      levels was found to be statistically significant in the ischemia group compared
      with the control and the sham groups (P < .05). The decrease in serum DAO levels
      was found to be statistically significant in the ischemia group compared with the
      control and the sham groups (P < .05). Diamine oxidase levels were found to
      decrease, beginning from the 1 hour after ischemia had been developed, and this
      rise was found to continue for 6 hours (P < .05). CONCLUSION: Serum DAO levels
      were decreased in ischemia. Further clinical and experimental investigations
      would be valuable to confirm the probable role of DAO in AMI.

PMID- 23158607
TI  - An eating disorder leading to wet beriberi heart failure in a 30-year-old woman.

PMID- 23158608
TI  - Spontaneous coronary artery dissection in a 14-year-old.

PMID- 23158609
TI  - Optimal initial anticoagulant therapy in pulmonary thromboembolism: randomized
      trial suggested.

PMID- 23158610
TI  - Instantaneous rigor or something else?

PMID- 23158611
TI  - What is the real incidence of oral tramadol-induced apnea? Is there any
      association between this type of apnea and mortality?

PMID- 23158612
TI  - Fatal dabigatran toxicity secondary to acute renal failure.

PMID- 23158613
TI  - Therapeutic hypothermia application vs standard support care in post resuscitated
      out-of-hospital cardiac arrest patients.
AB  - INTRODUCTION: Survival after cardiac arrest remains poor, especially when it
      occurs outside of hospital. In recent years, therapeutic hypothermia has been
      used to improve outcomes in patients who have experienced cardiac arrest,
      however, application to out-of-hospital cardiac arrest (OHCA) patients remains
      controversial. METHODS: A total of 175 OHCA patients underwent therapeutic
      hypothermia (TH), which was performed using large volume ice crystalloid fluid
      (LVICF) infusions after ICU admission. Ice packs and conventional cooling
      blankets were used to maintain a core body temperature of 33 degrees C, according
      to standard protocol for 36 hours. Patients in the control group received
      standard supportive care without TH. Hospital survival and neurologic outcomes
      were compared. RESULTS: There was no significant difference between the groups
      with regards to patient characteristics, underlying etiologies, and length of
      hospital stays. The duration of cardiac pulmonary resuscitation (CPR) was also
      similar. In the 51 patients that received TH, 14 were alive at hospital
      discharge. In the 124 patients belonging to the supportive care group, only 15
      were alive at hospital discharge (27.5% vs. 12.1%, p = 0.013). Approximately 7.9%
      of patients in the TH group had good neurologic outcomes (4 of 51) compared with
      the 1.7% (2 of 124) of patients in the supportive group (p = 0.04). There were no
      specific treatment-related complications. CONCLUSION: Therapeutic hypothermia can
      be safely applied to OHCA patients and can improve their outcome. Further large
      scale studies are needed to verify our results.

PMID- 23158614
TI  - Changes in expression of Nogo receptor 1 in hippocampus and cortex after
      cardiopulmonary resuscitation in rats.
AB  - The aim of this study was to investigate changes in Nogo receptor 1 (NgR(1))
      expression in the cerebrum after cardiopulmonary resuscitation (CPR) in rats.
      Cardiac arrest was induced by alternating current in 50 SD rats through
      transcutaneous electrical epicardium stimulation, and CPR was performed with the
      Utstein mode 6 minutes after cardiac arrest. Rats were killed 1, 3, and 7 days
      after CPR. We performed immunofluorescence with antibodies against NgR(1) to map
      the distribution of NgR(1) in the rat cerebrum, whereas quantitative polymerase
      chain reaction was performed for quantitative analysis of NgR(1) messenger RNA
      (mRNA). There was a striking transient up-regulation of the NgR(1) protein and
      mRNA in both the hippocampus and cortex in response to CPR. Nogo receptor 1
      proteins were strongly expressed in hippocampal neurons 1 and 3 days after CPR (P
      < .001 for 1 day and P < .05 for 3 days, vs the control group, respectively),
      which returned to the basal level 7 days after CPR. In the cortex, staining
      moderately increased 1 day after CPR and got the peak level after 3 days (P <
      .001), returning to normal expression levels on day 7. The levels of NgR(1) mRNA
      in the hippocampus and cerebral cortical cortex showed the same trend with
      staining. The changes were significantly different between day 3 and baseline in
      both the hippocampus and cortex (P < .05, respectively). Furthermore, there were
      significant differences between the hippocampus and cerebral cortical cortex at 1
      day and 3 days after the CPR (P < .05, respectively). There was a transient
      increase in NgR(1) in the vulnerable areas of the rat brain after CPR. Blockade
      of NgR(1) may be important in maintaining the high regenerative capacity of
      neurons during the time window when NgR(1) expression increases.

PMID- 23158616
TI  - MTV's Jersey Shore and the "GTL" mantra: time to lose the "Tanning".

PMID- 23158615
TI  - Clinical, laboratory, and educational challenges of diuretic doping.

PMID- 23158618
TI  - The current state of dermatology training: a national survey of graduating
      dermatology residents.

PMID- 23158617
TI  - Oral cholestyramine is not an effective treatment for uncomplicated
      erythropoietic protoporphyria.

PMID- 23158619
TI  - Short incubation photodynamic therapy with methylaminolevulinate and no occlusion
      for the treatment of actinic keratoses.

PMID- 23158620
TI  - Pain and nonmelanoma skin cancer in transplant patients.

PMID- 23158621
TI  - Photosensitivity disorders in children: part I.
AB  - Photosensitivity disorders in children encompass a diverse group of diseases.
      Compared to adult patients, underlying systemic disorders, including genetic or
      metabolic defects, are common causes in pediatric photosensitivity disorders.
      Photosensitivity in a child should be suspected if the child develops a sunburn
      reaction in sun-exposed sites after limited sun exposure. Diagnosis of a
      photodermatosis is made based on careful history taking and a physical
      examination. Early recognition and prompt diagnosis are essential to minimize
      long-term complications associated with inadequate photoprotection. In part I of
      this continuing medical education article, immunologically mediated
      photodermatoses, photodermatoses caused by exogenous photosensitizers, and the
      cutaneous porphyrias will be covered.

PMID- 23158622
TI  - Photosensitivity disorders in children: part II.
AB  - Photosensitivity disorders in children encompass a diverse group of diseases.
      Some inherited disorders manifest with photosensitivity early in life. Specific
      extracutaneous association may be the clue to diagnosis in this group of
      pediatric photodermatoses. Part II of this 2-part review covers hereditary
      photodermatoses caused by defects in nucleotide excision repair, double strand
      break repair, or localized or systemic biochemical abnormalities. Diagnosis and
      management of photoaggravated dermatoses are also discussed. Sun protection
      strategies are required in all patients with evidence of photosensitivity. Early
      recognition and prompt diagnosis is essential to minimize the long-term
      complications associated with inadequate photoprotection.

PMID- 23158625
TI  - Intractable chronic pruritus as the only manifestation of IgE hypersensitivity to
      Anisakis.

PMID- 23158626
TI  - Escitalopram oxalate (Lexapro)-induced acneiform eruption.

PMID- 23158627
TI  - Palmar squamous cell carcinoma successfully treated by intra-arterial infusion
      chemotherapy.

PMID- 23158628
TI  - Acute myeloid leukemia presenting with cutaneous infiltrates in a patient
      receiving etanercept for chronic lymphocytic vasculitis.

PMID- 23158629
TI  - Treatment of 2 patients with mycosis fungoides with alitretinoin.

PMID- 23158630
TI  - Multiple lesions of primary cutaneous nodular amyloidosis in Sjogren syndrome.

PMID- 23158631
TI  - Facial erythematous annular plaques: a case of annular Demodex facial dermatitis?

PMID- 23158632
TI  - Lichen sclerosus et atrophicans leading to joint contractures: restoration of
      joint mobility by extracorporeal photopheresis.

PMID- 23158633
TI  - Vasculitis and panniculitis associated with vemurafenib.

PMID- 23158634
TI  - Heat-induced squamous cell carcinoma of the lower extremities in a wildlands
      firefighter.

PMID- 23158635
TI  - Drug-induced subacute cutaneous lupus erythematosus associated with doxorubicin.

PMID- 23158636
TI  - Dermatoscopic evolution of dysplastic nevi showing high-grade dysplasia in a
      metastatic melanoma patient on vemurafenib.

PMID- 23158637
TI  - Sialoblastoma: an unexpected diagnosis.

PMID- 23158638
TI  - Recalcitrant severe hidradenitis suppurativa successfully treated with
      cyclosporine A.

PMID- 23158639
TI  - Short anagen syndrome in a girl with curly dark hair and consanguineous parents.

PMID- 23158640
TI  - Optic neuritis associated with tumor necrosis factor-alfa antagonists for the
      treatment of psoriasis.

PMID- 23158641
TI  - Skin ulcers mimicking pyoderma gangrenosum in a patient with MTHFR polymorphism.

PMID- 23158642
TI  - Sweet syndrome in a field of radiation therapy.

PMID- 23158643
TI  - Keratosis pilaris-like eruption observed during the experimental PLX 4032
      studies.

PMID- 23158644
TI  - Capillary malformation-arteriovenous malformation syndrome: identification of a
      family with a novel mutation.

PMID- 23158645
TI  - Minocycline-induced Sweet syndrome (acute febrile neutrophilic dermatosis).

PMID- 23158646
TI  - Familial follicular mucinosis: a case letter.

PMID- 23158647
TI  - Cryotherapy for primary cutaneous B-cell lymphoma.

PMID- 23158648
TI  - Weft hair extensions causing a distinctive horseshoe pattern of traction
      alopecia.

PMID- 23158649
TI  - A case of lead poisoning manifesting as oral mucosal erosions and crusted skin
      lesions.

PMID- 23158650
TI  - Salmonella Dublin faecal excretion probabilities in cattle with different
      temporal antibody profiles in 14 endemically infected dairy herds.
AB  - This longitudinal field study investigated the hypothesis that persistently high
      antibody levels indicate a high risk of Salmonella Dublin shedding in animals in
      14 endemically infected dairy herds. A hierarchical multivariable logistic
      regression was used to analyse 6614 paired faecal cultures and four types of
      temporal antibody profiles from cattle aged >=180 days. Age and repeated
      measurements on animals nested within herds were taken into account. Overall, the
      prevalence of faecal shedders was low (0.3% and 2.8% in the lowest and highest
      risk groups, respectively). An important predictor of faecal shedding was young
      age. There was a significant, but modest increase in risk in cattle with
      persistently high or recently increased antibody levels, but no difference
      between these two groups. Contrary to previous recommendations, the detection of
      carriers by the use of repeated antibody testing is not likely to be a plausible
      control option in most Salmonella Dublin-infected dairy herds.

PMID- 23158651
TI  - Review of recent outcome data of disorders of sex development (DSD): emphasis on
      surgical and sexual outcomes.
AB  - This paper is a review of some of the recent publications regarding outcome of
      DSD patients, with an emphasis upon surgical and sexual outcomes. Currently
      available outcome studies of patients with DSDs have limitations because of
      multiple factors, including lack of representative patient sampling, and lack of
      adequate information concerning both medical and surgical care, and
      psychological, social and family support. The most frequent reports involve
      females with 21-alpha-hydroxylase deficiency congenital adrenal hyperplasia
      (CAH). This most common form of DSD, if one excludes hypospadias and
      cryptorchidism, is an excellent example of a form of DSD in which all aspects of
      outcome, regarding surgery, sexual functionality and sensitivity, psychological
      input and endocrine hormonal therapy, carry a major role. The goals of therapy
      include a surgical outcome with a good cosmetic appearance and functionality with
      potential for sexual intercourse with sufficient sensitivity for satisfactory
      responsiveness. Endocrine replacement therapy should provide a normal adrenal
      hormonal milieu, while sex steroid therapy may be indicated. Psychological care
      should be provided from birth with gradual transition primarily to the patient,
      including basic counseling with full disclosure, although adjustment depends upon
      the patient's personality and parents' abilities and acceptance. Among forms of
      DSD involving gonadal insufficiency, hormonal replacement therapy should provide
      physiologic levels. Among females, estrogen therapy enhances healing after
      feminizing surgery and is required from puberty throughout adult life to maintain
      femininity, sexual organs and bone health, and enhance gender and sexuality.
      Among males, appropriate testosterone therapy maintains stamina, muscle tone,
      bone health, libido, sexual potency and general well-being, while benefit for
      healing after genital surgery is unclear. Further, outcome is clearly related to
      predominant cultural factors. Outcome studies should include evaluation of all of
      these factors.

PMID- 23158652
TI  - Psychosocial determinants of the intention to use a chlamydia home self-test:
      awareness of risk behaviour and test accuracy are important elements of
      educational interventions.
AB  - BACKGROUND: The aim of the present study was to investigate the association
      between psychosocial variables and the intention to use a chlamydia (Chlamydia
      trachomatis) home self-test, to enable information to be tailored to the target
      population. METHODS: A cross-sectional survey was carried out among an internet
      panel. A questionnaire was sent to a sample of 227 panelists in October 2006. A
      multiple linear regression analysis was conducted to assess the predictive value
      of the psychosocial factors for the intention to test. RESULTS: The response rate
      was 88% (n=200). Respondents with higher intentions to use a home self-test were
      younger, perceived themselves to be more susceptible to chlamydia, had more
      personal experience with chlamydia, felt a stronger moral obligation to do a test
      and had a higher level of response efficacy than those with lower intentions.
      CONCLUSIONS: This study provides topics for educational interventions aimed at
      encouraging chlamydia testing in general, and at developing a more effective use
      of home self-test. Awareness of personal behaviour and information about the
      probability of false positive and false negative test results with home self
      tests should be elements of these interventions.

PMID- 23158653
TI  - Pulmonary lymphangitic carcinomatosis as a primary manifestation of gastric
      carcinoma in a young adult: a case report and review of the literature.
AB  - BACKGROUND: Lymphangitic carcinomatosis as a manifestation of gastric carcinoma
      is rare. The presenting symptoms are misleading and nonspecific, often resulting
      in delayed diagnosis. CASE PRESENTATION: We present a case of a 24 year old male
      with progressive dyspnea. Initial radiologic assessment suggested interstitial
      lung disease, which was subsequently treated with antibiotics and
      corticosteroids. However, endoscopy and whole body diffusion-weighted magnetic
      resonance imaging revealed a metastatic gastric cancer with the presence of
      lymphangitic carcinomatosis. CONCLUSIONS: Pulmonary lymphangitic carcinomatosis
      is a rare manifestation of metastatic gastric cancer. Patients present with
      severe but non-specific respiratory complaints. Definitive diagnosis can be
      achieved by transbronchial biopsy. Prognosis is poor and optimal treatment is not
      defined. Whole body diffusion-weighted magnetic resonance imaging is a promising
      imaging tool for the diagnosis of metastatic gastric cancer.

PMID- 23158655
TI  - [Hepatitis B virus reactivation in patients receiving chemotherapy with breast
      cancer].

PMID- 23158654
TI  - Reduced cervical cancer incidence and mortality in Canada: national data from
      1932 to 2006.
AB  - BACKGROUND: High levels of participation in cervical screening are reported in
      Canada from the 1970's as a result of early uptake of the Pap smear and universal
      Medicare. Despite recommendations to the contrary, the programs have featured
      early age of initiation of screening and frequent screening intervals. Other
      countries have achieved successful outcomes without such features. We analyzed
      national data to better understand mortality and incidence trends, and their
      relationships to screening. METHODS: The Canadian Cancer Registry, National
      Cancer Incidence Reporting System, and the Canadian Vital Statistics Database
      were used to measure mortality and incidence rates. Cases and deaths from
      invasive cervical cancer were classified by 5 year age groups at diagnosis and
      death (15 to 19 years through to 80 to 84 years), year of diagnosis (1972 to
      2006), and year of death (1932 to 2006). Probabilities of developing and dying
      from cervical cancer were calculated for age-specific mortality and incidence.
      The proportion of women reporting a timely Pap test was estimated for 1978 to
      2006. RESULTS: Cervical cancer mortality has declined steadily from a peak of
      13.5 to 2.2 per 100,000 (83%,) between 1952 and 2006, and 71% between 1972 and
      2006. Incidence of invasive cervical cancer has declined by 58% since 1972. These
      declines have occurred more among older age groups than younger. Invasive
      cervical cancer incidence and mortality is less in each successive birth cohort
      of women. Participation rates in screening are high especially in women under age
      50. CONCLUSIONS: Despite increasing risk factors for cervical cancer, both
      incidence and mortality have declined over time, across age groups, and across
      birth cohorts. Earlier increasing mortality (1932 - 1950) was likely related to
      improved classification of cancers and the early subsequent reduction (1950 -
      1970) to improved treatment. Recent improvements in incidence and mortality are
      likely due to high rates of screening. For women under age 30 years there are low
      rates of disease but lesser improvement related to screening.

PMID- 23158656
TI  - [Controversies in corticosteroid treatment in influenza].

PMID- 23158657
TI  - [Relationship between the response of breast cancer to neoadjuvant chemotherapy
      and PI3K/mTOR pathway].
AB  - OBJECTIVE: To explore the relationship between the status of PI3K/mTOR pathway
      and the therapeutic efficacies of neoadjuvant chemotherapy for breast cancer.
      METHODS: A total of 105 patients receiving 4-6 cycles of taxane-based neoadjuvant
      chemotherapy at our centre between January 2009 and November 2010 were recruited
      into this retrospective study. The expressions of PTEN, p-AKT (Ser473) and p-mTOR
      (Ser2448) were detected by immunohistochemistry before neoadjuvant chemotherapy.
      We employed pathology to evaluate the therapeutic efficacies and considered
      complete response (G4) & pathologic complete response (PCR) as efficacious.
      Fourfold table Chi-square test and binary Logistic regression were used to
      analyze the relationship between the above features and therapeutic efficacies.
      RESULTS: The overall efficacy rate of neoadjuvant chemotherapy was 58.1% (61/105)
      and the PCR rate 27.6% (29/105). The positive expression rates of PTEN, p-AKT and
      p-mTOR were 52.4% (57/105), 68.6% (72/105) and 43.8% (46/105) respectively.
      Fourfold table Chi-square test showed the difference between p-mTOR and
      therapeutic efficacy was significant statistically (P = 0.003) and also the
      difference between p-mTOR and PCR (P = 0.001). Binary Logistic regression showed
      the difference between p-mTOR and therapeutic efficiency was significant
      statistically, and also the difference between p-mTOR and PCR (both P < 0.01).
      The differential expressions of p-mTOR and p-AKT were statistically significant
      (P = 0.000) and so were those of p-AKT and PR (P = 0.035). CONCLUSIONS: The
      status of p-mTOR has predictive values for taxane-based neoadjuvant chemotherapy.
      The patients with a low level of p-mTOR are more responsive to thermotherapy
      while those with a high level of p-mTOR have a worse efficacy.

PMID- 23158658
TI  - [Leptin promotes the expression of hTERT via STAT3 in breast cancer cells].
AB  - OBJECTIVE: To discussion the in vitro molecular mechanism of leptin promoting the
      expression of hTERT in breast cancer cells. METHODS: The hTERT mRNA expression of
      STAT3 knockdown on leptin-induced hTERT was measured by reverse transcription
      polymerase chain reaction (RT-PCR). Determine the expression of hTERT protein
      after different treatments in MCF7 by Western blot. Chromatin immunoprecipitation
      assay (ChIP) was performed to detect the binding of STAT3 to hTERT promoter in
      MCF7. Luciferase assay was used to confirm the effects of leptin and STAT3
      phosphorylation inhibitor on the transcriptional activity of hTERT promoter.
      RESULTS: The RT-PCR analysis showed that knockdown of STAT3 significantly reduced
      the leptin-induced transcription of hTERT. Western blot showed that the
      expression of hTERT were 3.109 +/- 0.051 and 1.025 +/- 0.031 after leptin or both
      of leptin and AG490 treatments. The results of CHIP showed that the mRNA of
      control and leptin (160 ng/ml) treatment were 1 and 3.311 +/- 0.017. Leptin
      increased the combination of STAT3 and hTERT promoter. Luciferase assay showed
      that when the concentration of leptin was 160 ng/ml, the hTERT promoter activity
      was 80.98 +/- 0.18 while the control was 20.76 +/- 0.31. After AG490 treatment,
      the hTERT promoter activity was 18.65 +/- 0.32,significantly reduced the leptin
      induced activity of hTERT promoter. CONCLUSION: Leptin/STAT3 signaling is a novel
      pathway for the up-regulation of hTERT expression in breast cancer cells.

PMID- 23158659
TI  - [Significance and expression of p53, p21(Cip1/WAF1) and Gadd45alpha in breast
      neoplasm tissues].
AB  - OBJECTIVE: To explore the expression and significance of p53, p21(Cip1/WAF1) and
      Gadd45alpha protein in breast cancer and their correlations with
      clinicopathologic features and prognosis in breast cancer. METHODS: The
      expressions of p53, p21(Cip1/WAF1) and Gadd45alpha proteins were determined by
      immunohistochemical staining. The relationship between these three proteins and
      clinicopathologic features in breast cancer was analyzed by chi(2) test and
      Spearman's rank correlation analysis. And the survival analyses were performed
      with the Kaplan-Meier method and Cox regression. The differences between the
      curves were examined with the two-tailed Log-rank test. RESULTS: In 133 cases of
      invasive breast cancer, the positive rates of p53, p21(Cip1/WAF1) and Gadd45alpha
      protein were 58.6%, 47.4% and 41.4% respectively. The expressions of
      p21(Cip1/WAF1) and p53 in cancer were significantly higher than those in the
      adjacent mammary gland tissue (P < 0.05) while the expression of Gadd45alpha was
      lower than that in the control mammary gland tissue (P < 0.05). The positive rate
      of p21(Cip1/WAF1) was correlated with the histological stage, local recurrence
      and positive C-erbB-2. And the positive rate of Gadd45alpha was correlated with
      the histological stage, lymph node metastasis, metastasis and positive estrogen
      receptor/progesterone receptor (ER/PR). The positive rate of p53 was correlated
      with the lymph node metastasis and TNM stage. Spearman's rank correlation
      analysis showed that p21(Cip1/WAF1) was correlated positively with p53, p53
      negatively with Gadd45alpha while p21(Cip1/WAF1) had no correlation with
      Gadd45alpha. With the follow-up data, Kaplan-Meier analysis showed that
      p21(Cip1/WAF1), Gadd45alpha, p53, lymph node metastasis, C-erbB-2 positive and
      TMN stage were associated with prognosis. Furthermore, Cox stepwise hazard
      analysis shows that p21(Cip1/WAF1), Gadd45alpha, C-erbB-2 and TMN stage were
      correlated with prognosis of breast cancer. Also the Kaplan-Meier analysis showed
      that p53(+)Gadd45alpha(-) and p53(+)p21(Cip1/WAF1)(+) were correlated with a poor
      prognosis of breast cancer. CONCLUSIONS: The expressions of p21(Cip1/WAF1),
      Gadd45alpha and p53 are associated with the clinicopathologic features and
      prognosis in breast cancer. Indicating a poor prognosis of breast cancer,
      p53(+)Gadd45alpha(-) and p53(+)p21(Cip1/WAF1)(+) may become independent indices
      for prognostic evaluations.

PMID- 23158660
TI  - [Roles of mitochondrial DNA somatic mutations in the pathogenesis of benign
      breast disease: a perspective from whole genome study].
AB  - OBJECTIVE: To explore the potential roles of mitochondrial DNA somatic mutations
      in benign breast disease based on the entire genome of mitochondrial DNA and
      elucidate the relationship between benign breast disease and breast cancer.
      METHODS: The genomic DNA of tumor tissue and peripheral blood in 28 benign breast
      disease patients with an average age of 33 years (range: 30 - 50) were extracted
      respectively. According to the revised Cambridge reference sequence and
      phylogenetic tree reconstruction, the mutations were identified and distinction
      was made between somatic mutations and private mitochondrial DNA mutations by
      haplogroup. RESULTS: Seven somatic mutations were detected. One mutation was
      located in the control region whereas the other six lied in the coding region.
      Further analyses revealed that, out of these 6 coding-region mutations, 4 were
      non-synonymous and would introduce the changes of amino acids. CONCLUSION: The
      mutations of mitochondrial DNA may play potential roles in the occurrence and
      development of benign breast disease.

PMID- 23158661
TI  - [Genotype and haplotype analysis of peroxisome proliferators activated receptor
      alpha gene and the risk of essential hypertension].
AB  - OBJECTIVE: PPARalpha, which is expressed in the liver, heart, skeletal muscle,
      and kidney, regulates lipid and lipoprotein metabolism. The aim of this study was
      to investigate the association between the PPARalpha gene and essential
      hypertension (EH) using a haplotype-based cohort study in a Chinese-Han
      population. METHODS: 820 subjects (270 males, 550 females) were genotyped for the
      three single-nucleotide polymorphisms used as genetic marker for the PPARalpha
      gene (rs1800206, rs4253778 and rs135539). Individual polymorphism and haplotype
      data were available for analyses. RESULTS: In the dominant model, the presence of
      the G allele of rs1800206 and the C allele of rs135539 were at a decreased risk
      of EH (OR = 0.48, 95%CI 0.40 - 0.64, P < 0.01; OR = 0.75, 95%CI 0.62 - 0.93, P <
      0.01, respectively). A 3.16-fold increase (95%CI 1.86 - 6.94, P = 0.002) in the
      risk of the development of EH was observed in homozygous genotype (CC) of
      rs4253778 compared to carriers of GG genotype (co-dominant model). The A-G-V and
      C-G-V haplotype (established by rs135539, rs4253778, rs1800206) was associated
      with a statistically significant decreased risk of EH (OR = 0.56, 95%CI 0.33 -
      0.83, P = 0.027; OR = 0.53, 95%CI 0.30 - 0.84, P = 0.033, respectively).
      CONCLUSION: These results may help to clarify the role of PPARalpha gene in EH
      and the evaluation of its polymorphisms and haplotypes as being characterized as
      genetic decreased risk factors for EH.

PMID- 23158662
TI  - [Identification of novel mutations in GATA6 gene associated with tetralogy of
      Fallot].
AB  - OBJECTIVE: To identify the novel mutations in the GATA6 gene associated with
      tetralogy of Fallot (TOF). METHODS: The clinical data and blood samples from 120
      unrelated Han Chinese TOF patients and 200 unrelated ethnically matched healthy
      controls were collected. The coding exons and flanking splice junctions of GATA6
      gene were amplified by polymerase chain reaction and sequenced by the technique
      of di-deoxynucleotide chain termination. The acquired sequences were aligned with
      those derived from GenBank by the aid of program BLAST to identify the sequence
      variations. The software ClustalW was applied for the conservation analysis of
      altered amino acids. The pathogenic probability for each sequence variation was
      predicted automatically by software MutationTaster. RESULTS: Three novel
      heterozygous missense GATA6 mutations were identified in 3 TOF patients.
      Specifically, the triplet substitutions of CTC for CCC at codon 73, CGC for AGC
      at codon 364 and GGC for GCC at codon 591, predicting the transitions of proline
      into leucine at amino acid residue 73 (p.P73L), serine into arginine at amino
      acid residue 364 (p.S364R) and alanine into glycine at amino acid residue 591
      (p.A591G), were detected. None of three mutations was observed in 200 healthy
      controls. A cross-species alignment of GATA6 encoded protein sequences showed
      that the mutated amino acids were highly conserved evolutionarily and all 3
      mutations were predicted to be pathogenic. CONCLUSIONS: Novel mutations are
      identified in the GATA6 gene associated with TOF. Such a finding may contribute
      to an early prophylaxis and therapy of TOF.

PMID- 23158663
TI  - [Relationship of amyloid-beta with vascular endothelial cell damage induced by
      diabetic serum].
AB  - OBJECTIVE: To explore the relationship of the impairment of human umbilical vein
      endothelial cell (HUVEC) with amyloid-beta. METHODS: HUVECs were cultured in the
      serum of patients with type 2 diabetes mellitus (DM) or serum of healthy control
      (HC), while fetal bovine serum (FBS) was used as a negative control. The
      proliferative activity of HUVEC were assessed by thiazolyl blue tetrazolium
      bromide (MTT) after 72 h. The supernatant concentrations of superoxide dismutase
      (SOD), maleic dialdehyde (MDA), nitric oxide (NO), amyloid-beta40 (Abeta40) and
      Abeta42 were measured after 0.5, 3 and 72 h respectively. RESULTS: Glycosylated
      hemoglobin values, fasting plasma glucose and fasting plasma Abeta40
      concentrations of diabetic patients were higher than those of healthy
      counterparts (P < 0.01). Proliferative activity of HUVECs in group DM were
      significantly lower than that of group HC. Both group and the time of
      intervention had crossover effects on the levels of MDA, SOD, NO and Abeta40
      ((163 +/- 64), (207 +/- 69), (286 +/- 75) ng/L in group DM; (146 +/- 76), (154 +/
      75), (161 +/- 72) ng/L in group HC after 0.5, 3 and 72 h, P < 0.05) and Abeta42
      ((48 +/- 46), (54 +/- 43), (79 +/- 44) ng/L in group DM; (41 +/- 12), (44 +/-
      16), (48 +/- 12) ng/L in group HC after 0.5, 3 and 72 h, P < 0.05). With the
      elongating time of intervention, the levels of SOD and NO decreased significantly
      in group DM and reached the lowest after 72 h while increased significantly in
      groups HC and FBS and peaked after 72 h. The concentrations of MDA, Abeta40 and
      Abeta42 increased significantly in all three groups while the fastest and marked
      increments were found in group DM (P < 0.01). Pearson correlation analysis showed
      that SOD was negatively correlated with Abeta40 (r = -0.482, P = 0.02) and
      Abeta42 (r = -0.422, P = 0.02) while MDA positively with Abeta40 (r = 0.418, P <
      0.05) and Abeta42 (r = 0.833, P < 0.05) after 72 h. CONCLUSION: Oxidative stress
      of vascular endothelial cells may be correlated with Abeta40 and Abeta42 in
      diabetes.

PMID- 23158664
TI  - [Different establishing conditions of hyperinsulinemic-euglycemic clamp technique
      among different groups].
AB  - OBJECTIVE: To compare the different establishing conditions of hyperinsulinemic
      euglycemic clamp technique among the groups of normal glucose tolerance (NGT),
      hyperinsulinemia with normal glucose (HINS) and impaired glucose tolerance (IGT).
      METHODS: The hyperinsulinemic-euglycemic clamp technique was applied to the study
      of methodology in 10 NGT, 11 HINS and 10 IGT subjects. Different establishing
      conditions were compared through variance analysis (ANOVA) among three groups.
      And the influencing factors resulting in these differences were analyzed through
      stepwise regression analysis. RESULTS: The serum insulin concentration of three
      groups were acutely raised and maintained at above 100 mU/L. During the steady
      stage, the blood glucose level remained stable and all coefficient variations
      were under 5%. The secretion of endogenous insulin and hepatic glucose production
      were completely inhibited during the test. Under these steady-state
      hyperinsulinemic-euglycemic conditions, the glucose infusion rate (M value) was
      equal to glucose disposal rate by all tissues in body, M value of three groups
      were as follows: (11.6 +/- 1.7), (6.1 +/- 1.9) and (6.0 +/- 1.5) mg*kg(-1)*min(
      1). During clamping, the peak and steady-state serum insulin concentrations of
      IGT and HINS groups were significantly higher than those of NGT group. Although
      the peak and steady-state serum insulin concentration of HINS group were higher
      than those of IGT group, the differences had no statistical significance (P =
      0.34, 0.11). The independent influencing factor of peak serum insulin
      concentration was waist-to-hip ratio (WHR) while the independent influencing
      factors of steady-state serum insulin concentration included insulin metabolic
      clearance rate (MCR) and body mass index (BMI). The peak and steady-state serum
      insulin concentrations were not the independent influencing factors of M value.
      CONCLUSION: During the establishment of hyperinsulinemic-euglycemic clamp
      technique, the differences in peak and steady-state serum insulin concentrations
      existed among NGT, HINS and IGT groups. But the differences do not influence the
      use of M value in the evaluation of insulin resistance.

PMID- 23158665
TI  - [Clinical features and outcome analyses of newly-diagnosed multiple myeloma with
      extramedullary involvements].
AB  - OBJECTIVE: To explore the clinical features and prognostic factors of newly
      diagnosed multiple myeloma (MM) with extramedullary (EM) involvements. METHODS:
      The clinical features, efficacies, survival rates and prognostic factors were
      retrospectively analyzed in 46 MM patients with EM (group A) from January 2000 to
      October 2011. And another 53 MM patients without EM (group B) were selected as
      the controls. RESULTS: The median age of Group A was 58 years. Compared with
      group B, the incidence of EM was associated with a higher level of beta2
      microglobulin (beta2-MG) and extensive bone disease. The most common location of
      EM was soft tissues. And the total effective rates of groups A and B were 58.5%
      (24/41) and 78.8% (41/52) respectively. The difference was statistically
      significant (P = 0.042). The median follow-up time was 28(2-88) months. The
      estimated overall survival (OS) of the patients with EM was significantly shorter
      than those without EM (42.6 vs 53.9 months, P = 0.009). Log-rank univariate
      analysis showed that the number of osteolytic lesions >= 3, beta2-MG >= 5.5 mg/L,
      hemoglobin <= 110 g/L and albumin <= 30 g/L were poor prognostic factors in MM
      patients with EM. Multivariate analysis with Cox model showed only the number of
      osteolytic lesions >= 3 (OR = 2.327, 95%CI: 1.282 - 4.224) and beta2-MG >= 5.5
      mg/L (OR = 2.677, 95%CI: 1.092 - 6.566) were statistically significant.
      CONCLUSIONS: Multiple EM lesions may be involved in MM patients. For the patients
      with EM, the response to conventional chemotherapy is poor and the prognosis is
      unfavorable, especially for those with a high level of beta2-MG or the number of
      osteolytic lesions >= 3.

PMID- 23158666
TI  - [Meta-analysis of risk factors for recurrent pulmonary thromboembolism].
AB  - OBJECTIVE: To evaluate the risk factors of recurrent pulmonary thromboembolism
      (PTE) through Meta-analysis. METHODS: Chinese Journal Full-text Database, Chinese
      Biomedical Database, PubMed and Foreign Medical Journal Full-Text Service were
      searched for the paper relating to the risk factors of recurrent PTE from January
      1995 to May 2011. And the references of these studies were also examined.
      Observational studies (cohort & case control) were assessed according to the
      method of quality assessment suggested within the references. Randomized control
      trials (RCTs) were assessed by the Jadad scale. Software RevMan 5.1 was used to
      examine the heterogeneity of trials. The fixed or random effect model was pooled
      to calculate the risk ratio (RR). And the results were expressed by RR (95%CI).
      RESULTS: Forty-two trials including 36 909 cases of PTE and/or deep vein
      thrombosis were analyzed. And the following factors were relative to recurrence:
      elevated D-dimer (1.77 (1.34 - 2.36), P = 0.000), idiopathic PTE (1.82 (1.61 -
      2.05), P = 0.000), right ventricular dysfunction (RVD) (persistent RVD vs RVD
      regression (8.71 (2.38 - 31.91), P = 0.001); persistent RVD vs non-RVD (2.45
      (1.26 - 4.76), P = 0.008), short anticoagulation duration (1.73 (1.32 - 2.28), P
      = 0.000), increased endogenous thrombin generation capacity (1.89 (1.39 - 2.56),
      P = 0.000), elevated factor VIII (1.96(1.40 - 2.74), P = 0.000), positive
      antiphospholipid antibodies (5.64 (4.09 - 7.77), P = 0.000), anti-thrombin defect
      (2.45 (1.26 - 4.76), P = 0.008) and males (1.47 (1.06 - 2.03), P = 0.020), etc.
      When multiple factors co-existed, the risk of recurrence became more obvious.
      CONCLUSIONS: Elevated D-dimer, idiopathic PTE and many other factors may
      influence the recurrence of pulmonary embolism. And most recurrent patients have
      two or more factors.

PMID- 23158667
TI  - [Analysis of cytomegaloviral antigenemia test and re-test after antiviral
      chemotherapy in patients with autoimmune and non-autoimmune diseases].
AB  - OBJECTIVE: To retrospectively analyze the cytomegalovirus (CMV) antigenemia test
      and re-test after antiviral chemotherapy in patients with autoimmune and non
      autoimmune diseases. METHODS: CMV Brite kit and indirect immunofluorescence were
      used to detect CMVpp65 antigenemia in 6471 peripheral blood leukocyte specimens
      from 5325 clinic and hospitalized patients with clinically suspicious CMV
      infections from May 2008 to February 2012. And the positive results were defined
      as episodes of systemic CMV activity. RESULTS: In 6471 EDTA-treated peripheral
      blood specimens, 948 (14.6%) were found with positive CMV antigenemia. The
      average positive rate from 13 kinds of autoimmune diseases was 34.9% (670/1922)
      in which systemic lupus erythematosus patients had the highest (52.4%, 551/1052).
      Meanwhile, the average positive rate from 12 kinds of non-autoimmune diseases was
      only 6.1% (144/2367) in which it was 17.3% (27/156) in patients with
      respiratory/acute renal failure, acquired immunodeficiency syndrome (AIDS) and
      kidney transplant recipients. And 189 patients with positive antigenemia were re
      tested after antiviral chemotherapy and only 64 (33.9%) were converted
      negatively. CONCLUSIONS: Patients with autoimmune diseases have replaced
      traditionally immunocompromised patients, e.g. AIDS and kidney transplant
      recipient, to become the highest risk group of systemic CMV activity. Negative
      conversion rate of CMV antigenemia is low after antiviral chemotherapy.

PMID- 23158668
TI  - [Logistic regression analysis of platelet transfusion effects in cases of cancer
      patients].
AB  - OBJECTIVE: To explore the influencing factors of platelet transfusion effects in
      cancer patients. METHODS: A total of 363 cases of cancer patients undergoing
      platelet transfusion at our hospital from January 1, 2010 to June 30, 2011 were
      enrolled. Only one transfusion was randomly selected for each patient for single
      factor analysis. Then a binary Logistic regression analysis was performed with
      transfusion effects as a dependent variable and the variables with P <= 0.2 as
      covariates in single-factor analysis. RESULTS: Among them, there were 280
      effective and 83 ineffective transfusions with an overall effective rate of
      77.1%. The single-factor analysis revealed that the P values were < 0.05 for age,
      platelet transfusion history, fever and antibiotic. Logistic analysis of multiple
      variables showed that platelet transfusion history (1-4 times compared to none,
      OR = 1.969,95%CI: 1.135 - 3.417; >= 5 times compared to none, OR = 5.260,95%
      CI:2.344 - 11.806), antibiotic (OR = 2.020,95%CI: 1.139 - 3.583), fever(OR =
      1.789,95%CI: 1.015 - 3.153) and storage days of platelets (OR = 1.559,95%CI:
      1.112 - 2.186) were independent risk factors. CONCLUSIONS: Influenced by multiple
      factors, the effects of platelet transfusion may be improved through reducing
      unreasonable transfusions, using fewer storage days of platelets and avoiding
      transfusions during fever and antibiotic uses.

PMID- 23158669
TI  - [Expression of peroxiredoxin 6 in gastric cancer and its clinical significance].
AB  - OBJECTIVE: To elucidate the significance of anti-oxidant protein peroxiredoxin 6
      (Prx6) expression in gastric cancer (GC) tissue. METHODS: Eighty-six GC tissues
      and 69 para-cancer tissues from surgically resected specimens were included. And
      the clinico-pathological data were collected by reviewing medical records. Tissue
      microarray and immunohistochemistry (IHC) were used to detect Prx6 protein
      expression in tissues. RESULTS: Prx6 protein was predominantly expressed in
      cytoplasm. Its expression rate in GC tissues (32.6%, n = 28) was significantly
      lower than that in para-cancer normal tissues (94.2%, n = 65, P < 0.05). And its
      protein overexpression rate in well and moderately-differentiated GC tissues was
      significantly higher than that in lowly-differentiated ones (39.6% (21/53) vs
      6.1% (2/33), P < 0.05). Prx6 expression in gastric cancer tissues was not
      significantly related to age and sex of patients, lesion site, depth of invasion,
      clinical staging, vascular invasion and liver metastasis. CONCLUSIONS: The level
      of Prx6 protein is lower in GC tissues than that in normal para-cancer ones. And
      it is significantly correlated with the differentiation degree of GC.

PMID- 23158670
TI  - [Experimental studies of effects of hydrogen-rich saline in rats with severe
      acute pancreatitis].
AB  - OBJECTIVE: To explore the mechanism and effectiveness of inducing severe acute
      pancreatitis (SAP) with saline saturated hydrogen in rats. METHODS: Based on a
      random number table, 54 Sprague-Dawley rats were divided into 3 groups: control,
      SAP and treatment (n = 18 each). The model of SAP was established by a retrograde
      injection of 5% sodium taurocholate into biliary-pancreatic duct. The treatment
      group received an injection of 5 ml/kg hydrogen-rich saline into tail vein at 1 h
      post-modeling. The control group underwent only pancreatic tipping. All rats were
      exsanguinated under anesthesia by aortal puncture after 24 hours. The serum
      levels of tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6) and
      interleukin-18 (IL-18) in 3 groups were measured by enzyme-linked immunosorbent
      assay (ELISA). The expression of TNF-alphamRNA in pancreatic tissue was measured
      by reverse transcription (RT)-PCR. And intercellular adhesion molecule-1 (ICAM-1)
      in pancreatic tissue was measured by immunohistochemistry. The pancreatic tissues
      were harvested to examine the microscopic changes. The levels of malonic aldehyde
      (MDA), myeloperoxidase (MPO), superoxide dismutase (SOD) and glutathione (GSH) in
      pancreatic tissue was measured by specific kits. RESULTS: The pathological scores
      of pancreatic tissue were significantly lower in the treatment group than those
      in the SAP group (9.7 +/- 2.0 vs 13.2 +/- 2.5, P < 0.05). The serum level of TNF
      alphawas significantly lower in the treatment group than that in the SAP group
      ((88 +/- 17) vs (1171 +/- 18) pg/ml, P < 0.05). And the serum levels of IL-6 and
      IL-18 were lower in the treatment group than those in the SAP group ((25.2 +/-
      5.9) vs (37.3 +/- 4.6) ng/L, (401 +/- 100) vs (439 +/- 103) ng/L, both P < 0.05).
      As compared with the SAP group, the levels of MDA and MPO decreased significantly
      in the treatment group ((8.2 +/- 2.8) vs (14.7 +/- 2.7) nmol/mg, (0.040 +/-
      0.011) vs (0.170 +/- 0.071) U/g, both P < 0.05). However, the levels of SOD and
      GSH significantly higher than those of the treatment group ((22.1 +/- 1.3) vs
      (15.1 +/- 1.7) U/mg, (4.8 +/- 0.4) vs (2.5 +/- 0.3) U/mg, both P < 0.05). The
      expressions of TNF-alpha mRNA and ICAM-1 in pancreatic tissues were lower than
      those of the treatment group (0.33 +/- 0.17 vs 0.94 +/- 0.31, 2.0 +/- 0.4 vs 2.8
      +/- 0.8, both P < 0.05). CONCLUSION: Hydrogen-rich saline can decrease the levels
      of inflammatory mediators and reduce the pathological damage of pancreas through
      the inhibition of oxidative stress.

PMID- 23158671
TI  - Cerebellar liponeurocytoma: case report.
AB  - Liponeurocytoma (lipomatous medulloblastoma) is a rarely and recently described
      tumor. We report an additional case of this uncommon lesion in an adult and we
      describe its clinical, radiological and histological features. A 45-year-old
      woman presented with symptoms and signs of increased intracranial pressure and
      cerebellar dysfunction. Computed tomography (CT) and magnetic resonance imaging
      (MRI) scans showed a heterogenous poorly circumscribed mass situated within the
      cerebellar vermis. After complete tumour resection, pathologic examination with
      immunohistochemical study confirmed the diagnosis. The postoperative course after
      18 months was favorable with no evidence of tumor recurrence.

PMID- 23158672
TI  - Do Malawian women critically assess the quality of care? A qualitative study on
      women's perceptions of perinatal care at a district hospital in Malawi.
AB  - BACKGROUND: Malawi has a high perinatal mortality rate of 40 deaths per 1,000
      births. To promote neonatal health, the Government of Malawi has identified
      essential health care packages for improving maternal and neonatal health in
      health care facilities. However, regardless of the availability of health
      services, women's perceptions of the care is important as it influences whether
      the women will or will not use the services. In Malawi 95% of pregnant women
      receive antenatal care from skilled attendants, but the number is reduced to 71%
      deliveries being conducted by skilled attendants. The objective of this study was
      to describe women's perceptions on perinatal care among the women delivered at a
      district hospital. METHODS: A descriptive study design with qualitative data
      collection and analysis methods. Data were collected through face-to-face in
      depth interviews using semi-structured interview guides collecting information on
      women's perceptions on perinatal care. A total of 14 in depth interviews were
      conducted with women delivering at Chiradzulu District Hospital from February to
      March 2011. The women were asked how they perceived the care they received from
      health workers during antepartum, intrapartum and postpartum. They were also
      asked about the information they received during provision of care. Data were
      manually analyzed using thematic analysis. RESULTS: Two themes from the study
      were good care and unsatisfactory care. Subthemes under good care were: respect,
      confidentiality, privacy and normal delivery. Providers' attitude, delay in
      providing care, inadequate care, and unavailability of delivery attendants were
      subthemes under unsatisfactory care. CONCLUSIONS: Although the results show that
      women wanted to be well received at health facilities, respected, treated with
      kindness, dignity and not shouted at, they were not critical of the care they
      received. The women did not know the quality of care to expect because they were
      not well informed. The women were not critical of the care they received because
      they were not aware of the standard of care. Instead they had low expectations.
      Health workers have a responsibility to inform women and their families about the
      care that women should expect. There is also a need for standardization of the
      antenatal information that is provided.

PMID- 23158673
TI  - Use of whole-genome sequencing for outbreak investigations.

PMID- 23158674
TI  - Whole-genome sequencing for analysis of an outbreak of meticillin-resistant
      Staphylococcus aureus: a descriptive study.
AB  - BACKGROUND: The emergence of meticillin-resistant Staphylococcus aureus (MRSA)
      that can persist in the community and replace existing hospital-adapted lineages
      of MRSA means that it is necessary to understand transmission dynamics in terms
      of hospitals and the community as one entity. We assessed the use of whole-genome
      sequencing to enhance detection of MRSA transmission between these settings.
      METHODS: We studied a putative MRSA outbreak on a special care baby unit (SCBU)
      at a National Health Service Foundation Trust in Cambridge, UK. We used whole
      genome sequencing to validate and expand findings from an infection-control team
      who assessed the outbreak through conventional analysis of epidemiological data
      and antibiogram profiles. We sequenced isolates from all colonised patients in
      the SCBU, and sequenced MRSA isolates from patients in the hospital or community
      with the same antibiotic susceptibility profile as the outbreak strain. FINDINGS:
      The hospital infection-control team identified 12 infants colonised with MRSA in
      a 6 month period in 2011, who were suspected of being linked, but a persistent
      outbreak could not be confirmed with conventional methods. With whole-genome
      sequencing, we identified 26 related cases of MRSA carriage, and showed
      transmission occurred within the SCBU, between mothers on a postnatal ward, and
      in the community. The outbreak MRSA type was a new sequence type (ST) 2371, which
      is closely related to ST22, but contains genes encoding Panton-Valentine
      leucocidin. Whole-genome sequencing data were used to propose and confirm that
      MRSA carriage by a staff member had allowed the outbreak to persist during
      periods without known infection on the SCBU and after a deep clean.
      INTERPRETATION: Whole-genome sequencing holds great promise for rapid, accurate,
      and comprehensive identification of bacterial transmission pathways in hospital
      and community settings, with concomitant reductions in infections, morbidity, and
      costs. FUNDING: UK Clinical Research Collaboration Translational Infection
      Research Initiative, Wellcome Trust, Health Protection Agency, and the National
      Institute for Health Research Cambridge Biomedical Research Centre.

PMID- 23158675
TI  - Metabolic syndrome and obsessive-compulsive disorder: a naturalistic Italian
      study.
AB  - OBJECTIVE: The increased risk for metabolic syndrome (MetS) in individuals with
      schizophrenia and bipolar disorder has been documented. No study examined MetS in
      patients with obsessive-compulsive disorder (OCD), despite the fact that a great
      proportion of them are treated with antipsychotic addition. The aim of our study
      was to investigate the prevalence and the sociodemographic and clinical
      correlates of MetS in an Italian sample of patients with OCD. METHOD: Subjects
      with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text
      Revision, OCD and a Yale-Brown Obsessive-Compulsive Scale score >= 16 were
      included. Sociodemographic and clinical characteristics, current and lifetime
      pharmacological treatments, lifestyle information, and comorbidity for
      cardiovascular diseases and diabetes were collected. MetS was diagnosed according
      to the National Cholesterol Education Program Adult Treatment Panel III modified
      criteria. RESULTS: We enrolled 104 patients with OCD. MetS was present in 21.2%
      (95% confidence interval: 13.7%-30.3%) of the sample. Abdominal obesity was
      present in 36.5%, hypertension in 42.3%, high triglycerides in 23.1%, low high
      density lipoprotein cholesterol levels in 22.1% and fasting hyperglycemia in 4.8%
      of the sample. MetS was associated with cigarette smoking (duration of cigarette
      smoking), absence of physical activity, a higher body mass index and a greater
      proportion of obesity. Among pharmacological treatments, MetS was associated with
      the duration of the exposure (lifetime) to antipsychotics. CONCLUSIONS: This is
      the first study that examined the prevalence and correlates of MetS in a sample
      of patients with OCD. Our cross-sectional evaluation found a prevalence of MetS
      higher than those reported in the Italian general population, although the
      confidence interval encompasses the general population estimate reported.
      Patients with OCD on antipsychotic treatment are particularly at risk for MetS
      and should be carefully monitored for metabolic abnormalities and cardiovascular
      complications.

PMID- 23158676
TI  - Impact of seasonal and lunar cycles on psychological symptoms in the ED: an
      empirical investigation of widely spread beliefs.
AB  - OBJECTIVES: This study evaluates the impacts of seasonal and lunar cycles on
      anxiety and mood disorders, panic and suicidal ideation in patients consulting
      the emergency department (ED) with a complaint of unexplained chest pain (UCP).
      METHODS: Patients with UCP were recruited from two EDs. Psychiatric diagnoses
      were evaluated with the Anxiety Disorders Interview Schedule for DSM-IV. RESULTS:
      Significant seasonal effects were observed on panic and anxiety disorders, with
      panic more frequently encountered during spring [odds ratio (OR)=1.378, 95%
      confidence interval (CI)=1.002-1.896] and anxiety disorders during summer
      (OR=1.586, 95% CI=1.037-2.425). Except for one significant finding, no
      significant effects of lunar cycles were observed. These findings encourage ED
      professionals and physicians to abandon their beliefs about the influence of
      lunar cycles on the mental health of their patients. Such unfounded beliefs are
      likely to be maintained by self-fulfilling prophecies.

PMID- 23158678
TI  - Fluctuations in corneal curvature limit predictability of intraocular lens power
      calculations.
AB  - PURPOSE: To analyze fluctuations in corneal curvature over time. SETTING:
      Moorfields Eye Hospital NHS Foundation Trust, London, United Kingdom. DESIGN:
      Case series. METHODS: A 3-piece IOL was implanted in 1 eye and a 1-piece IOL in
      the other eye through a 3.2 mm clear corneal temporal incision. Keratometry was
      performed preoperatively and at several points in time postoperatively.
      Differences between measurements were analyzed by power vectors. Statistical
      significance was assessed by monovariate, bivariate, and trivariate paired t
      tests. Acute angle shifts were determined as differences between meridians at 2
      points in time. RESULTS: Fifty patients were enrolled. From preoperatively to 1
      year postoperatively, the changes in vector components (M, J0, J45) were,
      respectively, -0.02 diopter (D) +/- 0.23 (SD) (P=.38), -0.07 +/- 0.27 D (P=.02),
      and +0.04 +/- 0.25 D (P=.14). Corresponding changes from 1 year to 2 years
      postoperatively were +0.01 +/- 0.25 D (P=.73), +0.01 +/- 0.23 D (P=.83), and
      +0.01 +/- 0.16 D (P=.40). The meridian shift was -5 +/- 32 degrees (P=.13) from
      preoperatively to postoperatively and +3 +/- 22 degrees (P=.23) from 1 year to 2
      years. CONCLUSIONS: Surgically induced astigmatism was composed of slight
      flattening in the horizontal meridian and slight steepening in the oblique
      meridian but was insignificant in relation to random fluctuations, which were
      almost equally large between postoperative measurements 1 year apart. The
      fluctuations were not due to imprecision in measurement. FINANCIAL DISCLOSURE:
      Dr. Norrby is a retiree from Abbott Medical Optics, Inc., and holder of a small
      amount of stock. Dr. Findl is scientific advisor to Abbott Medical Optics, Inc.
      No other author has a financial or proprietary interest in any material or method
      mentioned.

PMID- 23158677
TI  - Implementation of preventive mental health services for children of physically
      ill parents: experiences in seven European countries and health care systems.
AB  - OBJECTIVE: Parental physical disease is a family issue, but families' minor
      children are seldom considered. The current study analyzed experiences with
      implementation of counseling for families with physically ill parents and minor
      children during a European multisite pilot project. METHOD: Implementation
      protocols of seven European partner centers collaborating in a joint research
      project were analyzed by Mayring's qualitative content analysis. Both an
      inductive approach and a deductive approach were chosen. Satisfaction of families
      and therapists was considered based on information from three partner centers.
      RESULTS: Satisfaction with counseling was rather high. Mentioned problems
      referred to aspects related to liaison partners, family-related aspects and
      physicians' concerns. Recommendations related to contacting families, liaising
      with other professions, implementing counseling together with a research project,
      and training. Results are integrated in the current dissemination literature.
      CONCLUSION: Successful implementation was mostly determined by aspects of
      interdisciplinary cooperation and communication, perceived relative advantage and
      organizational premises. With regard to this kind of innovative child-centered
      family mental health services, top-down and bottom-up implementation strategies
      should be combined, and strategies of maintenance and sustainability should be
      considered from the very beginning.

PMID- 23158679
TI  - Laser in situ keratomileusis for high astigmatism in myopic and hyperopic eyes.
AB  - PURPOSE: To evaluate outcomes after laser in situ keratomileusis (LASIK) in
      highly astigmatic myopic and hyperopic eyes. SETTING: University eye clinic.
      DESIGN: Retrospective case series. METHODS: Eyes with more than 2.0 diopters (D)
      of astigmatism were identified from patient records. The mean preoperative
      cylinder was -3.92 D +/- 0.82 (SD) in myopic eyes and -4.42 +/- 1.10 D in
      hyperopic eyes. Patients were examined preoperatively and 3 months
      postoperatively. Laser in situ keratomileusis was performed with a Visumax
      femtosecond laser and a MEL-80 excimer laser. Preoperative and postoperative
      refractions were converted to polar values. Induced torsion and achieved
      correction of sphere and cylinder were determined. RESULTS: After 3 months, the
      mean sphere was 0.48 +/- 0.68 D in myopic eyes and the mean cylinder -0.97 +/-
      0.52 D. Spherical equivalent (SE) correction was 0.05 +/- 0.42 D from target.
      Astigmatism was 0.77 +/- 0.62 D undercorrected (P<.01), and the mean induced
      torsion was -0.18 +/- 0.51 D (P=.02). Astigmatic undercorrection was 21% of the
      intended correction. In hyperopia, the mean 3-month refraction was 0.79 +/- 0.83
      D in sphere and -1.38 +/- 0.90 D in cylinder. The SE refraction was -0.01 +/-
      0.71 D from target. Astigmatism was 1.17 +/- 0.81 D undercorrected (P<.01), with
      no significant torsion. Intended and achieved astigmatic corrections were
      correlated, with astigmatism being 28% undercorrected. CONCLUSIONS: Laser in situ
      keratomileusis in highly astigmatic eyes precisely corrected SE refraction but
      led to astigmatic undercorrection, particularly in hyperopia. Little to no
      torsion of the cylinder axis was induced.

PMID- 23158680
TI  - Topography-guided transepithelial photorefractive keratectomy for irregular
      astigmatism using a 213 nm solid-state laser.
AB  - PURPOSE: To explore the use of the Pulsar Z1 solid-state 213 nm photorefractive
      laser platform in topography-guided transepithelial photorefractive keratectomy
      (PRK) for irregular astigmatism. SETTING: Moorfields Eye Hospital, London, United
      Kingdom. DESIGN: Prospective clinical case series. METHODS: Patients with
      irregular astigmatism after previous refractive surgery or corneal
      transplantation were treated with topography-guided transepithelial PRK.
      Preoperatively and 1-year postoperatively, corrected distance visual acuity
      (CDVA) and secondary outcome measures (including manifest refraction, contrast
      sensitivity, haze score, index of surface variation, root-mean-square higher
      order aberrations, and subjective visual change) were compared between groups.
      Adjunctive mitomycin-C was not used. RESULTS: Seven patients had previous
      refractive surgery, and 7 had previous corneal transplantation. All but 2
      patients with a marked haze response had subjective gains in vision and improved
      CDVA. Gains in CDVA for patients with irregular astigmatism after previous
      refractive surgery (median 2 lines gain; range 0 to 2 lines gained) were higher
      than for patients with irregular astigmatism after keratoplasty (median 0 lines;
      range 5 lines lost to 4 lines gained). Trends in secondary outcome measures were
      similar, with greater variation in post-keratoplasty patients. Haze scores were
      higher in post-keratoplasty patients. CONCLUSIONS: 213 nm topography-guided
      transepithelial PRK was easy to perform and well tolerated by patients with
      irregular astigmatism. Most patients gained CDVA; however, increased haze
      responses were observed in post-keratoplasty cases.

PMID- 23158681
TI  - Clinical outcomes after implantation of a new hydrophobic acrylic toric IOL
      during routine cataract surgery.
AB  - PURPOSE: To assess the clinical outcomes after implantation of a new hydrophobic
      acrylic toric intraocular lens (IOL) to correct preexisting corneal astigmatism
      in patients having routine cataract surgery. SETTING: Four hospital eye clinics
      throughout Europe. DESIGN: Cohort study. METHODS: This study included eyes with
      at least 0.75 diopter (D) of preexisting corneal astigmatism having routine
      cataract surgery. Phacoemulsification was performed followed by insertion and
      alignment of a Tecnis toric IOL. Patients were examined 4 to 8 weeks
      postoperatively; uncorrected distance visual acuity (UDVA), corrected distance
      visual acuity, manifest refraction, and keratometry were measured. Individual
      patient satisfaction with uncorrected vision and the surgeon's assessment of ease
      of handling and performance of the IOL were also documented. The cylinder axis of
      the toric IOL was determined by dilated slitlamp examination. RESULTS: The study
      enrolled 67 eyes of 60 patients. Four to 8 weeks postoperatively, the mean UDVA
      was 0.15 logMAR +/- 0.17 (SD) and the UDVA was 20/40 or better in 88% of eyes.
      The mean refractive cylinder decreased significantly postoperatively, from -1.91
      +/- 1.07 D to -0.67 +/- 0.54 D. No significant change in keratometric cylinder
      was observed. The mean absolute IOL misalignment from the intended axis was 3.4
      degrees (range 0 to 12 degrees). The good UDVA resulted in high levels of patient
      satisfaction. CONCLUSION: Implantation of the new toric IOL was an effective,
      safe, and predictable method to manage corneal astigmatism in patients having
      routine cataract surgery.

PMID- 23158682
TI  - Hog1 bypasses stress-mediated down-regulation of transcription by RNA polymerase
      II redistribution and chromatin remodeling.
AB  - BACKGROUND: Cells are subjected to dramatic changes of gene expression upon
      environmental changes. Stress causes a general down-regulation of gene expression
      together with the induction of a set of stress-responsive genes. The p38-related
      stress-activated protein kinase Hog1 is an important regulator of transcription
      upon osmostress in yeast. RESULTS: Genome-wide localization studies of RNA
      polymerase II (RNA Pol II) and Hog1 showed that stress induced major changes in
      RNA Pol II localization, with a shift toward stress-responsive genes relative to
      housekeeping genes. RNA Pol II relocalization required Hog1, which was also
      localized to stress-responsive loci. In addition to RNA Pol II-bound genes, Hog1
      also localized to RNA polymerase III-bound genes, pointing to a wider role for
      Hog1 in transcriptional control than initially expected. Interestingly, an
      increasing association of Hog1 with stress-responsive genes was strongly
      correlated with chromatin remodeling and increased gene expression. Remarkably,
      MNase-Seq analysis showed that although chromatin structure was not significantly
      altered at a genome-wide level in response to stress, there was pronounced
      chromatin remodeling for those genes that displayed Hog1 association. CONCLUSION:
      Hog1 serves to bypass the general down-regulation of gene expression that occurs
      in response to osmostress, and does so both by targeting RNA Pol II machinery and
      by inducing chromatin remodeling at stress-responsive loci.

PMID- 23158683
TI  - Human leukocyte antigens and Gaucher disease.
AB  - BACKGROUND: Gaucher disease (GD) is caused by the reduced activity of lysosomal
      enzyme glucocerebrosidase, which leads to the accumulation of glucocerebroside in
      macrophages and a chronic stimulation of the immune system. GD is divided into 3
      main types according to the presence or absence of neurological involvement and
      to its presentation (acute or chronic). Gaucher cells show an increase in their
      expression of HLA-DR antigens on their surface, and there is an increase in
      levels of antigen-presenting molecules. Over 100 diseases have already been
      associated to HLA antigens; however, this association has never been studied in
      GD. OBJECTIVES: To analyze the variability of HLA genes in a Southern Brazilian
      sample of GD patients, to compare it with controls, and to look for associations
      with clinical manifestations. METHODOLOGY: Thirty-one GD patients (24 mild, 4
      moderate, and 3 severe) were included in the study. They were typed for HLA A, B,
      and DR and compared to 250 healthy controls. The clinical data were obtained from
      the review of medical records. RESULTS/DISCUSSION: There was a significant
      difference in the frequency of B37 allele among patients when compared to
      controls (p=0.011, OR 13.28). An association was found between DR11 (p=0.008) and
      DR13 (p=0.011) alleles and the severity of the disease. DR11 allele seems to be
      associated to neurologic compromise, while DR13 seems to be associated to
      osteonecrosis. CONCLUSION: Our data suggest a possible association of HLA
      variants and GD. The HLA variants must be further studied, for they seem to be a
      phenotype-modifier factor for GD.

PMID- 23158684
TI  - Outbreak of skin and soft tissue infections in a hospital newborn nursery in
      Italy due to community-acquired meticillin-resistant Staphylococcus aureus USA300
      clone.
AB  - BACKGROUND: Community-acquired meticillin-resistant Staphylococcus aureus (CA
      MRSA) is responsible for severe infections in previously healthy people acquired
      in the community in different areas of the world. AIM: To report an outbreak of
      CA-MRSA in a hospital newborn nursery in northern Italy in September-October
      2010, its investigation and control measures. METHODS: The epidemiology of the
      outbreak is reported. The investigation included screening neonates, parents and
      staff for MRSA carriage. Molecular strain typing was performed on MRSA isolates.
      FINDINGS: The outbreak affected nine neonates with three severe infections. In
      addition, four mothers had postpartum mastitis, and three mothers and one father
      had skin infection. The outbreak strain belonged to the USA300 CA-MRSA clone.
      Asymptomatic carriage of the outbreak strain was found among neonates, parents
      and hospital staff. The implementation of appropriate infection control measures
      in the hospital terminated the outbreak. CONCLUSIONS: To our knowledge, this is
      the first report of a hospital outbreak caused by the USA300 CA-MRSA clone in
      Europe. It is important to reinforce infection control measures, particularly in
      high-risk groups, such as neonates, to prevent USA300 from becoming endemic in
      European hospitals.

PMID- 23158685
TI  - Ribotyping in the detection of Clostridium difficile outbreaks in a single
      university hospital.
AB  - Clostridium difficile infection (CDI) is the most important bacterial cause of
      hospital-acquired diarrhoea. Although reports of deaths associated with CDI have
      been decreasing since a peak in 2007 in England and Northern Ireland, it remains
      a major cause of morbidity and mortality. The Health Protection Agency's
      Clostridium difficile Ribotyping Network (CDRN) aims to provide information to
      help optimize the management of cases of CDI. This study assesses the value of
      ribotyping to detect outbreaks of potential strains causing severe disease.

PMID- 23158686
TI  - Structure out of chaos: functional brain network analysis with EEG, MEG, and
      functional MRI.
AB  - The brain is the characteristic of a complex structure. By representing brain
      function, measured with EEG, MEG, and fMRI, as an abstract network, methods for
      the study of complex systems can be applied. These network studies have revealed
      insights in the complex, yet organized, architecture that is evidently present in
      brain function. We will discuss some technical aspects of formation and
      assessment of the functional brain networks. Moreover, the results that have been
      reported in this respect in the last years, in healthy brains as well as in
      functional brain networks of subjects with a neurological or psychiatrical
      disease, will be reviewed.

PMID- 23158687
TI  - Systematic review of health-related quality of life models.
AB  - BACKGROUND: A systematic literature review was conducted to (a) identify the most
      frequently used health-related quality of life (HRQOL) models and (b) critique
      those models. METHODS: Online search engines were queried using pre-determined
      inclusion and exclusion criteria. We reviewed titles, abstracts, and then full
      text articles for their relevance to this review. Then the most commonly used
      models were identified, reviewed in tables, and critiqued using published
      criteria. RESULTS: Of 1,602 titles identified, 100 articles from 21 countries met
      the inclusion criteria. The most frequently used HRQOL models were: Wilson and
      Cleary (16%), Ferrans and colleagues (4%), or World Health Organization (WHO)
      (5%). Ferrans and colleagues' model was a revision of Wilson and Cleary's model
      and appeared to have the greatest potential to guide future HRQOL research and
      practice. CONCLUSIONS: Recommendations are for researchers to use one of the
      three common HRQOL models unless there are compelling and clearly delineated
      reasons for creating new models. Disease-specific models can be derived from one
      of the three commonly used HRQOL models. We recommend Ferrans and colleagues'
      model because they added individual and environmental characteristics to the
      popular Wilson and Cleary model to better explain HRQOL. Using a common HRQOL
      model across studies will promote a coherent body of evidence that will more
      quickly advance the science in the area of HRQOL.

PMID- 23158688
TI  - Production of a solid fuel using sewage sludge and spent cooking oil by immersion
      frying.
AB  - Sewage sludge and spent cooking oil are two main waste sources of modern Chinese
      cities. In this paper, the immersion frying method using spent cooking oil as the
      heating medium was applied to dry and convert wet sewage sludge into a solid
      fuel. The drying and oil uptake curves were plotted to demonstrate the fry-drying
      characteristics of the sewage sludge. Parametric studies were carried out to
      identify the governing parameters in the frying drying operation. It was found
      that at frying oil temperatures of 140-160 degrees C, the wet sewage sludge could
      be dried completely in 6-9 min and converted into a solid fuel with a high
      calorific value of 21.55-24.08 MJ/kg. The fuel structure, chemical components,
      pyrolysis and combustion characteristics were investigated and the experimental
      results showed the solid fuel had a porous internal structure and a low ignition
      temperature of 250 degrees C due to presence of oil. The frying drying mechanism
      was also discussed.

PMID- 23158689
TI  - Anodic oxidation of salicylic acid on BDD electrode: variable effects and
      mechanisms of degradation.
AB  - The degradation of 100mL of solution with salicylic acid (SA) in the pH range 3.0
      10.0 has been studied by anodic oxidation in a cell with a boron-doped diamond
      (BDD) anode and a stainless steel cathode, both of 3 cm(2) area, by applying a
      current of 100, 300 and 450 mA at 25 degrees C. Completed mineralization is
      always achieved due to the great concentration of hydroxyl radical (OH) generated
      at the BDD surface. The mineralization rate increases with increasing applied
      current, but decreases when drug concentration rises from 200 mg L(-1).
      Nevertheless, the pH effect was not significant. During oxidation it was observed
      that catechol, 2,5-dihydroxylated benzoic acid, 2,3-dihydroxylated benzoic acid
      and hydroquinone were formed as aromatic intermediates. In addition, ion
      exclusion chromatography allowed the detection of fumaric, maleic, oxalic and
      formic as the ultimate carboxylic acid.

PMID- 23158690
TI  - Grafting 3-mercaptopropyl trimethoxysilane on multi-walled carbon nanotubes
      surface for improving on-line cadmium(II) preconcentration from water samples.
AB  - In the present study, the performance of multi-walled carbon nanotubes (MWCNTs)
      grafted with 3-mercaptopropyltrimethoxysilane (3-MPTMS), used as a solid phase
      extractor for Cd(2+) preconcentration in a flow injection system coupled to flame
      atomic absorption spectrometry (FAAS), was evaluated. The procedure involved the
      preconcentration of 20.0 mL of Cd(2+) solution at pH 7.5 (0.1 mol L(-1) buffer
      phosphate) through 70 mg of 3-MPTMS-grafted MWCNTs packed into a minicolumn at
      6.0 mL min(-1). The elution step was carried out with 1.0 mol L(-1) HCl. Fourier
      transform infrared (FTIR) spectroscopy, scanning electron microscopy (SEM) and
      energy dispersive spectroscopy (EDS) were used to estimate the extent of the
      MWCNT chemical modification. The 3-MPTMS-grafted MWCNTs provided a 1.68 times
      improvement in the sensitivity of the Cd(2+) FAAS determination compared to the
      unsilanized oxidized MWCNTs. The following parameters were obtained:
      preconcentration factor of 31.5, consumptive index of 0.635 mL, sample throughput
      of 14 h(-1), and concentration efficiency of 9.46 min(-1). The analytical curve
      was constructed in the range of 1.0-60.0 MUg L(-1) (r=0.9988), and the detection
      and quantification limits were found to be 0.15 MUg L(-1) and 0.62 MUg L(-1),
      respectively. Different types of water samples and cigarette sample were
      successfully analyzed, and the results were compared using electrothermal atomic
      absorption spectrometry (ETAAS) as reference technique. In addition, the accuracy
      of proposed method was also checked by analysis of certified reference material
      NIST SRM 1573a (tomato leaves) and standard reference material NIST SRM 1643e
      (trace elements in natural waters).

PMID- 23158691
TI  - Adsorption performance of titanium dioxide (TiO2) coated air filters for volatile
      organic compounds.
AB  - The photocatalytic oxidation (PCO) technology as an alternative method for air
      purification has been studied for decades and a variety of PCO models indicate
      that the adsorption of reactants on the catalyst surface is one of the major
      physical and chemical processes occurring at a heterogeneous photocatalytic
      reaction. However, limited study explored the adsorption effect of a
      photocatalyst. This study carried out a systematic evaluation of adsorption
      performance of titanium dioxide (TiO(2)) coated fiberglass fibers (FGFs), TiO(2)
      coated carbon cloth fibers (CCFs), and original CCFs air filters at various
      relative humidity conditions for nine volatile organic compounds. TiO(2)/FGFs,
      TiO(2)/CCFs, and CCFs were characterized by SEM for morphology and N(2)
      adsorption isotherm for BET surface area and pore structure. A bench-scale
      adsorption test setup was constructed and adsorption tests were performed at
      various relative humidity conditions and four different injected concentrations
      for each compound. The isothermal adsorption curves at low concentration levels
      were obtained and they were well described by Langmuir isotherm model. It was
      noticed that there were significant differences between the adsorption behaviors
      and photocatalytic activities of TiO(2)/FGFs and TiO(2)/CCFs. It was concluded
      that adsorption performance is closely related to the characteristics of
      substrates and therefore, the development of a substrate with high adsorption
      ability is a promising trend for improving the performance of the UV-PCO
      technology.

PMID- 23158692
TI  - Mechanochemical degradation of tetrabromobisphenol A: performance, products and
      pathway.
AB  - Tetrabromobisphenol A (TBBPA) is the most widely used brominated flame retardant
      (BFR), which has received more and more concerns due to its high lipophilicity,
      persistency and endocrine disrupting property in the environment. Considering the
      possible need for the safe disposal of TBBPA containing wastes in the future, the
      potential of mechanochemical (MC) destruction as a promising non-combustion
      technology was investigated in this study. TBBPA was co-ground with calcium oxide
      (CaO) or the mixture of iron powder and quartz sand (Fe+SiO(2)) in a planetary
      ball mill at room temperature. The method of Fe+SiO(2) destructed over 98% of
      initial TBBPA after 3h and acquired 95% debromination rate after 5h, which showed
      a better performance than the CaO method. Raman spectra and Fourier transform
      infrared spectroscopy (FTIR) demonstrated the generation of inorganic carbon with
      the disappearance of benzene ring and CBr bond, indicating the carbonization and
      debromination process during mechanochemical reaction. LC-MS-MS screening showed
      that the intermediates of the treatment with Fe+SiO(2) were tri-, bi-, mono
      brominated BPA, BPA and other fragments. Finally all the intermediates were also
      destroyed after 5h grinding. The bromine balance was calculated and a possible
      reaction pathway was proposed.

PMID- 23158693
TI  - Two simultaneous botulism outbreaks in Barcelona: Clostridium baratii and
      Clostridium botulinum.
AB  - Botulism is a severe neuroparalytic disorder that can be potentially life
      threatening. In Barcelona, Spain, no outbreaks had been reported in the past 25
      years. However, in September 2011, two outbreaks occurred involving two different
      families. A rare case of Clostridium baratii which produced a neurotoxin F
      outbreak was detected in five family members who had shared lunch, and several
      days before that another family was affected by C. botulinum toxin A which was
      probably present in homemade pate.

PMID- 23158695
TI  - Clients' preferred methods of obtaining sexually transmissable infection or HIV
      results from Sydney Sexual Health Centre.
AB  - Given the documented benefits of using text messaging (short message service;
      SMS), the internet and email to deliver sexually transmissible infection (STI)
      test results, including high acceptability among clients, Sydney Sexual Health
      Centre (SSHC) aimed to identify which methods our clients preferred for receiving
      their results, using a cross-sectional survey. There was a preference for SMS
      (32%) for negative STI results, and for SMS (27%), phone call (27%) and in-person
      (26%) for negative HIV results. An in-person preference was shown for receiving
      positive STI results (40%) and positive HIV results (56%, P<0.001). While many
      clients would prefer to receive STI test results via text messages or phone call,
      many also still prefer a return visit, with this preference is dependent on the
      type and nature of the results. Our study suggests that, ideally, several options
      for obtaining results should be available.

PMID- 23158694
TI  - Small molecules in the treatment of systemic lupus erythematosus.
AB  - Advances in the understanding of the cellular biological events that underlie
      systemic lupus erythematosus (SLE) have led to the identification of key
      molecules and signaling pathways that are aberrantly expressed. The parallel
      development of small molecule drugs that inhibit or interfere with the specific
      perturbations identified, offers perspective for more rational, effective and
      less toxic therapy. In this review, we present data from preclinical and clinical
      studies of such emerging novel therapies with a particular focus on kinase
      inhibitors and other compounds that modulate signal transduction. Moreover, we
      highlight the use of chromatin-modifying medications, bringing attention to the
      central role of epigenetics in SLE pathogenesis. 

PMID- 23158696
TI  - Unilateral mydriasis due to a topical "anti-sweat" preparation.

PMID- 23158697
TI  - Fast and efficient lung disease classification using hierarchical one-against-all
      support vector machine and cost-sensitive feature selection.
AB  - To improve time and accuracy in differentiating diffuse interstitial lung disease
      for computer-aided quantification, we introduce a hierarchical support vector
      machine which selects a class by training a binary classifier at each node in a
      hierarchy, thus allowing each classifier to use a class-specific quasi-optimal
      feature set. In addition, the computational cost-sensitive group-feature
      selection criterion combined with the sequential forward selection is applied in
      order to obtain a useful and computationally inexpensive quasi-optimal feature
      set for the purpose of accelerating the classification time. The classification
      time was reduced by up to 57% and the overall accuracy was significantly improved
      in comparison with the one-against-all and one-against-one support vector machine
      methods with sequential forward selection (paired t-test, p<0.001). The reduction
      of classification time as well as the improvement of overall accuracy
      demonstrates promise for the proposed classification method to be adopted in
      various real-time and on-line image-based clinical applications.

PMID- 23158698
TI  - Two common profiles exist for genomic oligonucleotide frequencies.
AB  - BACKGROUND: It was reported that there is a majority profile for trinucleotide
      frequencies among genomes. And further study has revealed that two common
      profiles, rather than one majority profile, exist for genomic trinucleotide
      frequencies. However, the origins of the common/majority profile remain elusive.
      Moreover, it is not clear whether the features of common profile may be extended
      to oligonucleotides other than trinucleotides. FINDINGS: We analyzed 571
      prokaryotic genomes (chromosomes) and some selected eukaryotic nuclear genomes as
      well as other genetic systems to study their compositional features. We found
      that there are also two common profiles for genomic oligonucleotide frequencies:
      one is from low-GC content genomes, and the other is from high-GC content
      genomes. Furthermore, each common profile is highly correlated to the average
      profile of random sequences with corresponding GC content and generated according
      to first-order symmetry. CONCLUSIONS: The causes for the existence of two common
      profiles would mainly be GC content variations and strand symmetry of genomic
      sequences. Therefore, both GC content and strand symmetry would play important
      roles in genome evolution.

PMID- 23158700
TI  - Patient perceptions of pain management therapy: a comparison of real-time
      assessment of patient education and satisfaction and registered nurse
      perceptions.
AB  - Nurses must have an understanding of their patients' perception to assist in
      meeting analgesic goals. Adequate patient teaching is essential. The value of a
      simplified tool to assess patients' satisfaction has not been widely examined.
      This study examined if nurses' perceptions of their patients' satisfaction with
      pain management are congruent with patients' self-report, and if patients' level
      of satisfaction corresponds with the type of therapy used and adequacy of
      teaching related to their pain management plan. Data were collected though a
      survey in a community hospital. It was designed as an evaluative study of the
      variables in two nursing units and as a pilot study of the survey tool. Ratings
      of patient satisfaction by nurses (3.8 +/- 0.88 [mean +/- SD]) were similar to
      patients' self-ratings (4.08 +/- 1.06). Higher self-report of pain (visual analog
      scale 4.00 +/- 2.22) was associated with lower levels of satisfaction (3.80 +/-
      0.881). Patients reporting adequate teaching rated a higher satisfaction score
      (4.46) than patients reporting inadequate teaching [3.59; t (48) = -3.12; p =
      .003]. Patients receiving intravenous analgesia as needed had higher pain VAS
      scores (4.74) than patients receiving other analgesia protocols [3.37; t(48) = 
      2.26; p = .028]. Measuring patient satisfaction has become critical in evaluating
      adequacy of treatment. Factors that affect patients' satisfaction with pain
      management include the adequacy of teaching they receive and the type of therapy
      they are provided. A simple survey can be a useful tool in measuring
      satisfaction.

PMID- 23158701
TI  - Do ethnic differences still exist in pain assessment and treatment in the
      emergency department?
AB  - Although the provision of timely and appropriate analgesia is a primary goal of
      Emergency Department (ED) staff, pain continues to be undertreated and some
      evidence supports the existence of pain treatment disparities. Despite strong
      incentives from accreditation organizations, pain management in the ED may still
      be inconsistent and problematic. The purpose of this research study was to
      conduct a retrospective chart review to investigate pain assessment and treatment
      for 200 adults (>=18 years old) admitted to the ED suffering from long-bone
      fractures. An additional purpose was to investigate demographic variables,
      including ethnicity, to determine if they influenced pain assessment, pain
      treatment, and wait times in the ED. Although assessment and treatment of pain is
      universally recognized as being important and necessary to provide optimal
      patient care, only 52% of patients in this study were assessed using a pain
      intensity scale, with 43% of those assessed reporting pain as >=5 on a 0-10 pain
      intensity instrument. Pain medication was administered to 75% of the patients,
      but 25% of the patients received no medication. Only 24% of those receiving a
      pain medication were reassessed to determine pain relief. Compounding these
      problems were wait times for analgesia of >1 hour. Although the influence on pain
      management related to ethnicity was not a factor in this study, other findings
      revealed that undertreatment of pain, inadequate assessment, lack of
      documentation of pain, and lengthy wait times persist in the ED.

PMID- 23158702
TI  - Evaluating the feasibility and effect of using a hospital-wide coordinated
      approach to introduce evidence-based changes for pain management.
AB  - This action research project explored the feasibility and effect of implementing
      a hospital-wide coordinated approach to improve the management of pain. The
      project used a previously developed model to introduce three evidence-based
      changes in pain management. Part of this model included the introduction of 30
      pain resource nurses (PRNs) to act as clinical champions for pain at a local
      level. Both quantitative and qualitative measures were used to assess the
      feasibility and effect of the changes introduced. Quantitative data were gathered
      through a hospital-wide document review and assessment of the knowledge and
      attitude of the PRNs at two time points: time 1 before the introduction of the
      PRNs and time 2 near completion of the project (11 months later). A statistically
      significant improvement in the documentation of pain scores on admission and each
      nursing shift was apparent. However, no difference was found in the percentage of
      patients who had been prescribed opioids for regular pain relief that had also
      been prescribed and dispensed a laxative/aperient. Neither were any statistically
      significant decreases in patient pain scores observed. An assessment of the
      knowledge and attitudes of the PRNs showed an improvement from time 1 to time 2
      that was statistically significant. The qualitative data revealed that despite
      the barriers encountered, the role was satisfying for the PRNs and valued by
      other hospital staff. Overall, the results revealed that the new model of change
      incorporating PRNs was a useful and effective method for introducing and
      sustaining evidence-based organizational change.

PMID- 23158703
TI  - Acceptance of chronic neuropathic pain in spinal cord injured persons: a
      qualitative approach.
AB  - Chronic neuropathic pain (CNP) in spinal cord injury (SCI) is a significant
      problem that has physical, functional, and psychosocial repercussions beyond the
      consequences of SCI. The notion that acceptance may be a viable alternative to
      suffering when resolution of pain is unattainable was explored. Studies indicate
      that acceptance of pain is associated with lower pain intensity, less pain
      related anxiety and avoidance, less depression, less physical and psychosocial
      disability, more daily active time, and improved work status in patients who have
      other types of chronic pain. This exploratory qualitative study examined
      acceptance of pain in SCI individuals who have CNP. Grounded theory was used to
      develop a conceptual framework to describe acceptance in people with CNP and SCI.
      Data were obtained from in-depth interviews with seven SCI individuals. Six
      phases were identified, including: "comprehending the perplexity of CNP,"
      "seeking pain resolution," "acknowledging pain permanence," "redefining core
      values," "learning to live with the pain," and "integrating pain." Two driving
      forces, "increasing independence" and "evolving pain view," were noted to move
      the process of acceptance forward. The findings in this study suggest that
      acceptance of pain appeared to be beneficial in terms of reducing suffering and
      facilitating a more satisfying and fulfilling life in these SCI individuals. A
      decreased emphasis on continued searching for a cure for CNP and movement toward
      a self-management approach was associated with increased pain coping for these
      SCI individuals. Clinical implications suggest that early intervention to
      facilitate effective coping and an exploration of the notion of acceptance could
      be beneficial.

PMID- 23158704
TI  - Outcomes of follow-up visits to chronic nonmalignant pain patients.
AB  - Follow-up visits by clinical nurse specialists are beneficial for patients with
      various chronic conditions. It is unknown whether patients with chronic
      nonmalignant pain can achieve similar benefit. The aim of this study was to
      assess outcomes of follow-up visits by clinical nurse specialists to chronic
      nonmalignant pain patients regarding health-related quality of life (HRQoL),
      pain, opioid treatment, quality of sleep, and depression. A total of 102 patients
      were enrolled in a prospective randomized controlled trial during a 2-year period
      after discharge from multidisciplinary pain treatment and randomized to
      intervention or control group. Intervention group patients (n = 52) received home
      visits every fourth month for 2 years. The findings showed that HRQoL improved
      generally more in the intervention group. Statistically significant improvements
      were observed for physical function and bodily pain. Whereas the intervention
      group maintained the pain level on a visual analog scale, the control group
      reported more pain. During the observation period, the control group increased
      dosage of opioids whereas the intervention group maintained stable dosage. No
      significant effect on quality of life was found. Nurses identified signs of
      depression in 80% of their patients scoring depression on the simultaneous
      depression questionnaire, and thereby could refer patients to early treatment.
      Follow-up visits by clinical nurse specialists appeared to offer positive
      benefits to patients with chronic nonmalignant pain after discharge from
      multidisciplinary pain treatment. The intervention improved physical functioning,
      reduced bodily pain and pain intensity and prevented opioid dosage increase. Most
      episodes of depression were identified and referred to relevant treatment.

PMID- 23158706
TI  - [Recent progress and prospect of knee replacement].

PMID- 23158705
TI  - Effect of aromatherapy massage on dysmenorrhea in Turkish students.
AB  - The purpose of this study was to investigate the effect of aromatherapy massage
      on dysmenorrhea. The study used a quasiexperimental design with the subjects as
      their own control. Every participant applied both aromatherapy massage with
      lavender oil and placebo massage with odorless liquid petrolatum [soft paraffin].
      The population comprised 438 midwifery and nursing students. The 150 students who
      had declared that they had suffered from dysmenorrhea used a visual analog scale
      to indicate their level of pain. Higher scores reflected a greater severity of
      dysmenorrhea. Forty-four students volunteered to participate in the study. When
      the lavender massage and the placebo massage were compared, the visual analog
      scale score of the lavender massage was found to decrease at a statistically
      significant rate. This study showed that massage was effective in reducing
      dysmenorrhea. In addition, this study showed that the effect of aromatherapy
      massage on pain was higher than that of placebo massage.

PMID- 23158707
TI  - [Preliminary analysis of management for hospitalized elders with hip fractures].
AB  - OBJECTIVE: To analyze various clinical parameters of elderly hip fractures so as
      to improve the management of elder hip fractures in China. METHODS: The data of
      elder patients with hip fracture (primary diagnosis was fracture of femoral neck
      or intertrochanter) admitted into our department between 2002 to 2010 were
      collected. And the relevant clinical parameters included case number, age, ratio
      of concurrent chronic disease and duration and cost of hospitalization. The
      software of SAS was used for statistical analysis. RESULTS: A total of 1626
      patients (M/F = 547/1079) >= 65 yr old with femoral neck fracture were admitted.
      Average age was 74.7 +/- 6.4 yr (65 - 99) and annual average increasing rate 0.5%
      (-0.1% - 1.8%). The ratio of concurrent chronic disease was 53.3%. Average
      duration of hospitalization was 18.3 +/- 10.9 days (1 - 114) and annual average
      increasing rate was -6.3% (-19.2% - 8.4%). Average cost of hospitalization was 38
      758.04 +/- 24 558.15 yuan (76.8 - 339 987.49) and annual average increasing rate
      6.4% (-8.7% - 40.0%). A total of 892 patients (M/F = 362/530) >= 65 yr with
      femoral intertrochanteric fracture were admitted. Average age was 76.7 +/- 6.8 yr
      (65 - 105) and annual average increasing rate 1.3% (-1.8% - 4.3%). The ratio of
      concurrent chronic disease was 55.8%. Average duration of hospitalization was
      15.7 +/- 8.7 days (1 - 78) and annual average increasing rate -4.5% (-22.1% -
      8.0%). Average cost of hospitalization was 35 183.45 +/- 21 427.47 yuan (75.3 -
      148 150.41) and annual average increasing rate 18.3% (-3.7% - 79.9%). CONCLUSION:
      The number, age and therapeutic cost of elder patients with hip fracture are
      increasing continuously. Elderly hip fracture is becoming a serious problem of
      public health.

PMID- 23158708
TI  - [Cementless total hip arthroplasty for the management of advanced tuberculous
      coxitis].
AB  - OBJECTIVE: The question of whether a total joint arthroplasty should be attempted
      in a patient with a current or previous infection of tuberculosis continues to
      arouse controversy. The aim of this report was to evaluate the clinical outcomes
      of cementless total hip arthroplasty for the treatment of advanced tuberculosis
      of hip. METHODS: A total of 14 patients with advanced tuberculosis of hip treated
      by cementless total hip arthroplasty were retrospectively analyzed. For the
      patients with a definite diagnosis of tuberculosis and elevated levels of CRP (C
      reactive protein) and ESR (erythrocyte sedimentation rate) before surgery,
      preoperative antituberculous medications were prescribed for at least 2 weeks.
      The inflamed soft tissues and destroyed bones were completely curetted out at the
      time of operation. Twelve of 14 patients received one-stage cementless total hip
      arthroplasty after a thorough debridement. For the remaining 2 patients, two
      stage strategy was taken with cement articulating spacer implanted after a
      thorough debridement and followed by cementless total hip arthroplasty at 6-8
      months later. All patients were prescribed antituberculous medications
      postoperatively for the first 6 months. RESULTS: The mean Harris Hip Score (HHS)
      was 36 preoperatively and 87 at the last follow-up. Within an average follow-up
      period of 49 months (range: 27 - 77), only one patient had reactivation of
      tuberculosis 7 months after primary THA (total hip arthroplasty) and received
      resection arthroplasty. Another 13 patients had no reactivation of tuberculosis
      and revealed stability by bone ingrowth on both socket and femoral stem.
      CONCLUSION: Cementless total hip arthroplasty is a safe and effective procedure
      for advanced tuberculosis of hip. With a thorough debridement followed by a
      complete course of antituberculous chemotherapy, active tuberculous infection
      should not be considered a contraindication for THA. In patients whose diagnosis
      of tuberculosis is confirmed intraoperatively and with no preoperative
      antituberculous chemotherapy, or in those a thorough debridement can not be
      achieved, a two-stage surgery may be considered.

PMID- 23158709
TI  - [Treatment of anterior cruciate ligament injury with peroneus longus tendon].
AB  - OBJECTIVE: To evaluate the effects of anterior cruciate ligament reconstruction
      with peroneus longus tendon and observe the clinical outcomes of ankle joint
      after the resection of peroneus longus tendon. METHODS: From January 2006 to
      December 2009, 35 patients with anterior cruciate ligament injuries were
      recruited to undergo surgical procedures. There were 30 males and 5 females with
      an average age of 31.8 years (range: 21 - 56). All anterior cruciate ligament
      reconstructions underwent arthroscopy. All ligaments were reconstructed with
      peroneus longus tendon and fixed with absorb screw. The post-operative
      assessments included the followings:clinical evaluations, Lysholm knee score, KT
      3000 arthrometer evaluation and the American Orthopedic Foot and Ankle Society
      ankle-hindfoot scale AOFAS). RESULTS: All cases were followed up for an average
      follow-up period of 15 months (range: 12 - 24). The healing time was 6 - 15
      weeks.according to the Lysholm knee score, their outcomes were excellent (n =
      25), good (n = 6), fair (n = 3) and poor (n = 1). The average score was 97.2
      (range: 60 - 100). The rate of excellent and good was 88.6%; according to the KT
      3000 arthrometer evaluations, the outcomes were normal (n = 28), nearly normal (n
      = 4), abnormal (n = 2) and poor (n = 1). Preoperatively, the average anterior
      displacement was 11.59 +/- 1.25 mm and the average anterior displacement at final
      follow-up 1.76 +/- 1.83 mm. The average AOFAS score was 96.3 (range: 84 - 100).
      Lysholm knee score and KT-3000 arthrometer evaluation had statistical differences
      (P < 0.05) while AOFAS score showed no difference (P > 0.05). CONCLUSION:
      Peroneus longus tendon can be a good substitute of anterior cruciate ligament
      reconstruction. And its resection has no major influence for ankle joint.

PMID- 23158710
TI  - [Experimental research on repairing full-thickness articular cartilage defects by
      transplantation of autologous uncultured bone-marrow-derived mononuclear cells in
      combination with micro-fracture].
AB  - OBJECTIVE: To examine the feasibility of autologous uncultured bone-marrow
      derived mononuclear cells (BM-MNCs) in combination with microfracture in a full
      thickness articular cartilage defect model so as to provide experimental
      rationales for clinical applications. METHODS: A total of 40 rabbits were divided
      randomly into groups A, B, C and D (n = 10 each). In groups A and C, 5 ml marrow
      samples were harvested from left femur and then autologous BM-MNCs isolated. The
      full-thickness articular cartilage defects were made on femoral intercondylar
      fossa in right knees of rabbits. Group A: micro-fracture was made on cartilage
      defect and then autologous uncultured BM-MNCs-autologous fibrin gel complex
      implanted; Group B:the same micro-fracture was made on cartilage defect and
      autologous fibrin gel implanted; Group C:the cartilage defect was implanted with
      autologous uncultured BM-MNCs-autologous fibrin gel complex; Group D:the
      cartilage defect was implanted with autologous fibrin gel. Five rabbits were
      sacrificed at Weeks 8 and 12 post-transplantation in each group. And the
      reparative tissue samples evaluated grossly, histologically and
      immunohistochemically were graded according to the gross and histological scales.
      RESULTS: The statistical analyses of histological gradings at Weeks 8 and 12
      showed that group A was significantly better than groups B, C and D (P < 0.05),
      groups B and C were better than group D (P < 0.05) and each group at Week 12 was
      better than itself at Week 6 (P < 0.05). CONCLUSION: Both of micro-fracture and
      transplantation of uncultured autologous BM-MNCs plus autologous fiber gel can
      promote the repair of cartilage defects. The combined use of micro-fracture and
      autologous uncultured BM-MNCs promotes the regeneration of articular cartilage so
      that it may provide theoretical rationales for clinical applications.

PMID- 23158711
TI  - [A comparative study of N400 in generalized anxiety disorder versus obsessive
      compulsive disorder patients].
AB  - OBJECTIVE: To explore the features of events-related potentials (ERP) component
      N400 in generalized anxiety disorder (GAD) versus obsessive compulsive disorder
      (OCD) patients and understand the cognitive pattern and processing characteristic
      for Chinese characters. METHODS: ERP component N400 was recorded by Guangzhou
      Runjie WJ-1 ERP apparatus. And 41 GAD patients, 69 OCD patients and 58 normal
      controls (NC) were tested by the Chinese idioms ending with matching (congruent)
      or mismatching (incongruent) words. RESULTS: (1) Latencies: Significant
      differences were found of N400 latencies in ending words with the same
      pronunciation but different forms and meanings (NC: (377 +/- 40) ms, OCD: (395 +/
      43) ms, GAD: (396 +/- 43) ms, congruent; NC: (415 +/- 32) ms, OCD: (429 +/- 35)
      ms, GAD: (430 +/- 36) ms, incongruent), ending words with the same meaning but
      different pronunciations and forms (NC: (411 +/- 32) ms, OCD: (424 +/- 40) ms,
      GAD: (433 +/- 39) ms, incongruent), ending words with different pronunciations,
      forms and meanings (NC: (399 +/- 47) ms, OCD: (427 +/- 53) ms, GAD: (434 +/- 42)
      ms, congruent; NC: (442 +/- 36) ms, OCD: (465 +/- 35) ms, GAD: (474 +/- 35) ms,
      incongruent) (P < 0.05 - 0.01). Compared with NC, the N400 latencies were
      prolonged in GAD and OCD patients. Compared with OCD patients, the GAD patients
      also showed prolonged N400 latencies in ending words with different
      pronunciations, forms and meanings (incongruent situation). (2) Significant
      differences were found of N400 amplitudes in ending words with the same
      pronunciation but different forms and meanings (NC: (9 +/- 5) uV, OCD: (6 +/- 5)
      uV, GAD: (6 +/- 5) uV, congruent; NC: (11 +/- 6) uV, OCD: (5 +/- 4) uV, GAD: (6
      +/- 4) uV, incongruent), ending words with similar forms but different
      pronunciations and meanings (NC: (9 +/- 5) uV, OCD: (5 +/- 4) uV, GAD: (7 +/- 5)
      uV, congruent; NC: (14 +/- 6) uV, OCD: (6 +/- 5) uV, GAD: (9 +/- 7) uV,
      incongruent), ending words with different pronunciations, forms and meanings (NC:
      (9 +/- 5) uV, OCD: (5 +/- 4) uV, GAD: (5 +/- 3) uV, congruent; NC: (14 +/- 6) uV,
      OCD: (9 +/- 7) uV, GAD: (9 +/- 7) uV, incongruent) (P < 0.05 - 0.01). Compared
      with NC, N400 amplitudes decreased in GAD and OCD patients respectively. Compared
      with OCD patients, the GAD patients also showed elevated N400 amplitudes in
      ending words with similar forms but different pronunciations and meanings
      (congruent). CONCLUSION: The cognitive and emotional problems in GAD and OCD may
      be measured by N400 elicited by Chinese idioms. Notable N400 priming effects can
      be found in Chinese idioms.

PMID- 23158712
TI  - [Randomized controlled clinical trial of middle-dose cyclophosphamide plus
      methylprednisolone for myasthenia gravis patients in crisis].
AB  - OBJECTIVE: To evaluate the efficacy and safety of middle-dose cyclophosphamide
      plus methylprednisolone for myasthenia gravis (MG) patients in crisis. METHODS:
      For this prospective, open, parallel, randomized controlled trial, we recruited a
      total of 156 MG patients in crisis from January 1999 to October 2011 at
      Department of Neurology, First Affiliated Hospital, Sun Yat-sen University. They
      were divided into two groups of cyclophosphamide and control (n = 78 each). In
      the cyclophosphamide group, each received methylprednisolone 500 mg/d for 3 days,
      then tapered to 250 mg/d and tapered half every 3 days until 62.5 mg/d. Afterward
      an oral dose of prednisone was prescribed at 30 mg/d until the end of the trial.
      At the same time, an intravenous injection of cyclophosphamide was offered at 0.4
      g/d for 3 days and then 0.4 g/d every 3 days. In the control group, each received
      methylprednisolone alone. And the efficacies were assessed by absolute and
      relative MG scores. RESULTS: (1) There were 54 (69.2%) patients off-ventilation
      in 3 days in the cyclophosphamide group versus 36 (46.2%) patients in 8 - 14 days
      in the control group. Notable statistical significance existed between two groups
      (P = 0.000). (2) More than half of the patients in cyclophosphamide group with
      extremity weakness (n = 44, 56%) and dysphagia (n = 47, 60.3%) significantly
      improved in 10 - 14 days versus 28 days in the control group. Notable statistical
      significance existed between two groups (P = 0.000). (3) In the cyclophosphamide
      group, dyspnea disappeared in 54 (69.2%) patients when the dose reached 1.2 g.
      The recovery of dysphagia (n = 47, 60.3%) and extremity weakness (n = 44, 56.4%)
      occurred in more than half of the patients when the dose reached 2.8 g. Notable
      statistical significance existed among three groups (P = 0.000). (4) During the
      treatment period, there were 17 cases (21.8%) with pulmonary infection in the
      cyclophosphamide group versus 53 cases (67.9%) in the control group. Notable
      statistical significance existed between two groups (P = 0.000). (5) Brief and
      minor side effects appeared in the patients of the cyclophosphamide group.
      CONCLUSION: (1) The combined treatment of middle-dose cyclophosphamide and
      methylprednisolone for MG patients in crisis is both effective and safe. (2) When
      combined with methylprednisolone, 90% of patients with MG crisis are successfully
      off-ventilation when the dose of cyclophosphamide reaches 1.6 g.

PMID- 23158713
TI  - [Impact of lacrimal obstruction type on the efficacy of probing for congenital
      nasolacrimal duct obstruction].
AB  - OBJECTIVE: To explore the impact of lacrimal obstruction type on the efficacy of
      lacrimal probing in the treatment of congenital nasolacrimal duct obstruction.
      METHODS: We conducted a retrospective study in which 872 eyes of 741 children
      with congenital nasolacrimal duct obstruction underwent nasolacrimal duct probing
      under superficial anesthesia. Two types of obstructions were encountered during
      probing, i.e. simple and complex. They were divided into early (4 - 12 months)
      and late (1 - 4 years) groups based upon the age at the time of initial probing.
      Those refractory to the first probing underwent a second probing 4 weeks later.
      The main observation criterion was the success rate of probing. RESULTS: The
      success rate was 90.0% in early group versus 70.4% in late group (chi(2) =
      38.527, P < 0.01). No significant difference existed in the cure rate of simple
      or complex obstruction between two groups (chi(2) simple = 0.054, P = 0.815,
      chi(2) complex = 1.705, P = 0.192). The proportion of simple obstruction was
      94.4% in early group versus 62.2% in late group. Difference was statistically
      significant (chi(2) = 125.471, P < 0.01). The success rate of a second probing of
      simple obstruction was 61.9% in early group versus 68.2% in late group (chi(2) =
      0.324, P = 0.569). The success rate of a second probing of complex obstruction
      was 19.2% in early group versus 5.7% in late group (Fisher's exact test, P =
      0.125). For either group, the success rate of a second probing of simple
      obstruction was higher than that of complex obstruction (chi(2) early group =
      16.100, P < 0.01; chi(2) late group = 25.186, P < 0.01). CONCLUSION: Unsuccessful
      probing may result from the selection of complex obstructions. Probing should
      remain the first-line treatment in children above 1 year of age. The success rate
      with a second probing was significantly lower in patients of complex obstruction.
      Other surgical interventions, such as silicone tube intubation or balloon
      dacryocystoplasty, should be recommended instead of repeated probing for the
      patients of complex obstruction if an initial probing fails.

PMID- 23158714
TI  - [A comparison of double-lumen endotracheal tube with univent blocker and
      bronchial blocker during thoracic surgical anesthesia].
AB  - OBJECTIVE: To compare the effectiveness of lung isolation among double-lumen
      endotracheal tube, Univent blocker and bronchial blocker during thoracic surgical
      anesthesia. METHODS: A total of 120 patients undergoing elective thoracic surgery
      were enrolled. They were intubated with Mallinckrodt DLT (DLT group, n = 40),
      Univent blocker (UNI group, n = 40) and Coopdech bronchial blocker (BB group, n =
      40) after intravenous anesthesia induction. The following parameters were
      recorded:(1) time to initially position the assigned tube; (2) changes of mean
      arterial pressure (MAP) and heart rate (HR) at 5 min post-intubation; (3) lung
      collapse scores; (4) frequency of malpositions; (5) airway press and blood gas
      change during one lung ventilation (OLV); (6)postoperative sore throat at 24 h
      postoperation. RESULTS: No statistical difference existed in positioning three
      types of endotracheal tubes. But MAP and HR were higher at post-intubation in DLT
      group compared with the other 2 groups. No difference existed among the lung
      isolation devices in lung collapse scores at 5/10 min after pleural opening. As
      compared with the UNI and BB groups, Ppeak and Pplat increased while compliance
      decreased in DLT group during OLV. Statistical differences existed in tube
      malpositions among three groups (n = 4, DLT; n = 5, UNI; n = 8, BB). The
      incidence of postoperative sore throat was significantly higher in DLT group
      (70%) than the other two groups (37.5%, UNI; 22.5%, BB). CONCLUSION: As compared
      with DLT, Univent and Coopdech bronchial blocker may reduce the airway injury and
      improve the compliance during OLV. But there is a higher intraoperative incidence
      of tube malposition.

PMID- 23158715
TI  - [Perioperative airway management for the treatment of atlantoaxial surgical lysis
      and fixation through transoral approach].
AB  - OBJECTIVE: To explore the perioperative airway management for transoral surgical
      lysis in patients with irreducible atlantoaxial dislocation and posterior
      atlantoaxial or occipitocervical fixation. METHODS: Thirty patients undergoing
      surgical lysis through transoral approach with oral endotracheal intubation (OEI
      group) between September 2009 and June 2010 were recruited. And another 31
      patients underwent transoral surgical lysis from December 2008 to August 2009
      with percutaneous dilatational tracheostomy (PDT group). The time interval from
      artificial airway establishment to start of operation, the duration of
      nasogastric feeding, the incidence of respiratory complications and the
      postoperative length of hospital stay were compared between two groups. RESULTS:
      The time interval from artificial airway establishment to the start of operation
      in the OEI group was significantly shorter than that in the PDT group [(39 +/-
      15) vs (58 +/- 16) min, P < 0.01]. The duration for nasogastric feeding in the
      OEI group was significantly shorter than that in the PDT group [(6.0 +/- 1.2) vs
      (7.9 +/- 0.3) days, P < 0.01]. And the postoperative length of hospital stay was
      also shorter in the OEI group than that in the PDT group [(9.5 +/- 1.7) vs (11.8
      +/- 3.4) days, P < 0.01]. CONCLUSION: The management of perioperative airway with
      oral endotracheal intubation may avoid the complications of PDT, improve the
      utilizing efficiency of operating rooms and shorten the postoperative length of
      hospital stay.

PMID- 23158716
TI  - [Analysis of relevant factors of cerebral arteriovenous malformation with
      hemorrhage].
AB  - OBJECTIVE: To explore the influencing factors of bleeding in the patients with
      cerebral arteriovenous malformation (AVM) through observing its angioarchitecture
      with cerebral digital subtraction angiography (DSA) so as to decipher its
      hemorrhagic risks. METHODS: A total of 87 cases of cerebral AVM during the period
      of 2004-2010 underwent cerebral angiography by digital subtraction angiography.
      The relationships between bleeding and such factors as the site and size of
      masses of AVM, the type and site of supplying arteries, the number and pathway of
      venous drainage, the relationships between AVM and aneurysm in terms of location
      and venous tumor were determined by univariate analyses and binary Logistic
      regression with SPSS 18.0. RESULTS: Univariate analysis indicated that such
      factors as the site and size of masses, the type and site of supplying arteries,
      the number venous drainage, the relationships between AVM and aneurysm were
      positively correlated with hemorrhagic presentation. When stepwise multiple
      Logistic regression analysis was employed, only the size of AVM, the number of
      venous drainage and aneurysm were the independent predictors of hemorrhagic
      presentation. CONCLUSION: The size of masses of AVM, the number of venous
      drainage and aneurysm are the strong risk predictors for AVM hemorrhage.

PMID- 23158717
TI  - [Application of high-field intraoperative magnetic resonance imaging in
      stereotactic aspiration and drainage of hypertensive hematomas].
AB  - OBJECTIVE: To explore the application values of high-field intraoperative
      magnetic resonance imaging (MRI) in stereotactic aspiration and drainage of
      hypertensive hematomas. METHODS: During a period of August 2011 to January 2012,
      11 patients with hypertensive hemorrhage were examined preoperatively by
      conventional MRI and diffusion tensor imaging (DTI) with 1.5T intraoperative MRI
      system (Signa HDi, GE, USA) at Tianjin Medical University General Hospital. The
      anatomic relationship of corticospinal tract (CST) and hematoma was used for the
      operative planning with the neuronavigation planning workstation (iPlan Cranial
      3.0 software, BrainLab, Germany) for 3D reconstruction. During stereotactic
      surgery, intraoperative MRI scan was performed. According to the clearance rate
      of hematomas, the operators decided to finish the operation or update the
      operative planning to continue hematoma removal. All patients were reexamined by
      conventional MRI and DTI at Week 3 postoperation. Then comparative analysis was
      performed for the preoperative and postoperative integrity of CST. RESULTS: No
      death or severe complications occurred. All patients showed improvement of motor
      function and the postoperative integrity of CST. CONCLUSION: The intracranial
      condition may be monitored effectively by intraoperative MRI throughout surgery
      so as to increase the rate of hematoma removal and reduce the postoperative
      complications.

PMID- 23158718
TI  - [Diagnostic value of (18)F-labeled NaF positron emission tomography-computed
      tomography imaging in the detection of bone metastases in patients with lung
      cancer before treatment].
AB  - OBJECTIVE: To evaluate the diagnostic values of (18)F-sodium fluoride ((18)F-NaF)
      positron emission tomography/computed tomography (PET/CT) imaging in the
      detection of bone metastases of lung cancer. METHODS: A total of 107 lung cancer
      patients were diagnosed by histopathology and undergone (18)F-NaF PET-CT imaging.
      RESULTS: Among them, the histopathologically diagnosed tumors included
      adenocarcinoma (n = 47), squamous cell carcinoma (n = 19), small cell lung cancer
      (n = 4) and other malignant types (n = 34). Bone metastases occurred in
      adenocarcinoma (n = 19) and squamous cell carcinoma (n = 4).(18)F-NaF PET/CT
      imaging had a high sensitivity of 100% in the diagnosis of bone metastases with
      malignant lung tumors. And its specificity was 98.7%, accuracy 99% and positive
      predictive value 97.0%. CONCLUSION: (18)F-NaF PET-CT imaging can detect the bone
      metastases of lung cancer preoperatively with a high level of sensitivity and
      accuracy.

PMID- 23158719
TI  - [Study of functional magnetic resonance imaging repeatability of linguistic
      functional cortex].
AB  - OBJECTIVE: To explore the reproducibility and stability of brain functional area
      in the response of language tasks during Chinese word processing with functional
      magnetic resonance imaging (fMRI) by follow-up scanning so as to provide
      rationales for clinical preoperative localization and the mechanisms of recovery
      from aphasia. METHODS: The fMRI data were collected by scanning semantic and
      phonologic judgments in 15 healthy volunteers. Each subject was scanned twice by
      the same fMRI procedure of both language tasks with an interval of 1 month. By
      analyzing the effective overlapping average activation maps, the reproducibility
      of inter-subject imaging result for two language tasks were estimated by
      selecting the main language areas, such as Broca's area and Wernicke's area as
      the region of interest (ROI). By individually calculating the spatial distance of
      ROI centroid coordinates in the same activating range before and after test, the
      inter-subject stability in between-session was calculated quantitatively.
      RESULTS: Both language tasks activated more than one language-related brain areas
      in cerebral hemispheres. Both language tasks induced significant BOLD response in
      Broca's and Wernicke's areas with a tendency of left lateralization. The number
      of subjects in terms of the activation of both language tasks in Broca's and
      Wernicke's areas accounted over a half of the total subjects. As compared with
      the phonologic judgment task, the semantic judgment task showed better
      reproducibility in Broca's area. In the same spatial distance of ROI centroid
      coordinates, the stability of Broca's area was higher than that of Wernicke's
      area while the stability of semantic judgment in Broca's area higher than that of
      phonologic judgment. CONCLUSION: Such main language domains as Broca's and
      Wernicke's areas can be effectively activated by both semantic and phonologic
      judgments. By comparison, semantic judgment in Broca's area shows a higher level
      of reproducibility and stability. Thus it is applicable for clinical preoperative
      localization and the mechanisms of recovery from aphasia.

PMID- 23158720
TI  - [Clinical significance of combined detection of thinprep cytology test and high
      risk human papillomavirus hybrid capture 2 assay in the screening and recurrence
      predication of cervical intraepithelial neoplasia].
AB  - OBJECTIVE: To evaluate the clinical significance of combined detection of TCT and
      HR-HPV-HC2 assay in the screening and recurrence prediction of CIN. METHODS: A
      total of 725 patients with suspected cervical abnormalities received TCT plus HR
      HPV-HC2 detection and histopathological examinations.203 CINII-III patients
      received TCT and HC2 detection and histopathological examinations after treated
      with loop electrosurgical excision procedure or cold knife conization operation.
      The results of pathological examinations were gold standard. The sensitivity and
      specificity of TCT, HR-HPV-HC2 and TCT plus HR-HPV-HC2 were analyzed. RESULTS:
      The missed diagnosis and misdiagnosis rate of TCT and HC2 alone were 19.23%,
      12.50% and 48.15%, 74.07% and sensitivity and specificity 90.02%, 97.01% and
      51.85%, 17.76% respectively. The sensitivity, missed diagnosis rate and negative
      predictive value were 98.25%, 1.75% and 89.70% when TCT or HR-HPV-HC2 met the CIN
      diagnostic criteria. The specificity and positive predictive value were 58.95%
      and 72.80% when TCT and HR-HPV-HC2 met the CIN diagnostic criteria. The
      specificity of TCT or HR-HPV-HC2 alone was 80% for the prediction of recurrence
      at Month 6 postoperation. The specificity of TCT plus HR-HPV-HC2 was 98.27% for
      the prediction of recurrence at Month 3 postoperation and the negative predictive
      value was 98.75% at Month 6 postoperation. The sensitivity of TCT or HR-HPV-HC2
      was 97.22% for the prediction of recurrence at Month 3/6. And the negative
      predictive value was 99.17% at Month 6 postoperation. CONCLUSION: The combined
      detection of TCT and HR-HPV-HC2 may improve the sensitivity and specificity of
      CIN and the predication of its postoperative recurrence.

PMID- 23158721
TI  - [Intraoperative oculomotor nerve monitoring during skull base tumor surgery].
AB  - OBJECTIVE: To explore the intraoperative oculomotor nerve monitoring during skull
      base tumor surgery for injury avoidance. METHODS: The study was conducted from
      January 2006 to January 2012. Monitoring group:35 skull base tumor operations
      were monitored by neurophysiology (22 males and 13 females). CONTROL GROUP: 26
      skull base tumor operations without intraoperative monitoring were treated with
      microsurgery alone (16 males and 10 females). The prognoses of different groups
      were evaluated. RESULTS: Monitoring group:2 cases had injury of oculomotor nerve.
      One of them suffered mild diplopia and recovered one months later. Another one
      had blepharoptosis and mydriasis, reaction to light was absent and recovered six
      months later. CONTROL GROUP: 6 cases had injury of oculomotor nerve. Five of 6
      cases recovered six months later. And one showed no recovery after a 1-year
      follow-up. CONCLUSION: Intraoperative monitoring of oculomotor is essential for
      the protection of oculomotor nerve during skull base tumor surgery.

PMID- 23158722
TI  - [Differential invasion and metastasis capacities of methotrexate enantiomer
      resistant A549 cell lines].
AB  - OBJECTIVE: To study the differential in vitro motor and invasion capacities of
      methotrexate (MTX) enantiomer-resistant tumor cells. METHODS: The incremental
      concentrations and successive low-dose induction were employed to acquire the
      cell series resistant to 15 umol/L MTX enantiomer, namely L-(+)-MTX/A549 and D-(
      )-MTX/A549. Their drug-resistant indices were determined by MTT assay and their
      migration capacities by wound healing assay. Double soft-agar clone formation was
      used to detect the colony efficiency and size. And Transwell was employed to
      detect the in vitro movement and invasion capacity of three cell types. RESULTS:
      The resistance indices of L-(+)-MTX/A549 and D-(-)-MTX/A549 were (6.1 +/- 1.0)
      and (20.3 +/- 1.8) respectively. At 72 hours after wound healing assay, the
      number of L-(+)-MTX/A549 entering scratch zone was fewer than that of D-(-)
      MTX/A549; The numbers of colony formation in D-(-)-MTX/A549, L-(+)-MTX/A549 and
      parental cells were (50 +/- 7), (44 +/- 6), (52 +/- 7) and the rates of colony
      formation (1.68% +/- 0.23%), (1.49% +/- 0.18%), (1.73% +/- 0.23%) respectively.
      And there was no significant significance among three groups (P > 0.05). But the
      size of D-(-)-MTX/A549 was larger than that of L-(+)-MTX/A549. Transwell detected
      infiltration and invasion through artificial basement membrane Matrigel. The
      numbers of D-(-)-MTX/A549, L-(+)-MTX/A549 and parent cells were (267 +/- 30),
      (106 +/- 16) and (134 +/- 16) respectively. The data were significant between D-(
      )-MTX/A549 cells and L-(+)-MTX/A549 or parent cells (P < 0.05) but not
      significant between L-(+)-MTX/A549 and parent cells (P > 0.05). CONCLUSION: The D
      (-)-MTX-induced NSCLC A549 cells have greater motor and invasion capacities than
      those of L-(+)-MTX-induced ones. It suggests that MTX enantiomer has different
      capacities of tumor invasion and metastasis after acquiring resistance.

PMID- 23158723
TI  - [Net power and energy of cooled antenna microwave ablation:ex vivo versus in vivo
      results in porcine liver].
AB  - OBJECTIVE: To explore the net power and net energy of a cooled antenna radiator
      in ex vivo and in vivo porcine livers. METHODS: All animal experiments complied
      with the guidelines of our animal use committee. Microwave ablation (MWA) was
      performed in ex vivo and in vivo porcine livers with a cooled-shaft antenna in
      different microwave ablation parameter groups (50, 80 and 110 W for 10 min). The
      energy losses from the microwave antenna or cables were calculated. And the net
      power, net energy and the relationship between net power and power readout were
      determined. RESULTS: When the power displayed by the machine indicated 50 W, 80 W
      and 110 W, the net power during MWA was 31.3 +/- 0.6, 47.3 +/- 0.8 and 62.1 +/-
      0.9 W ex vivo and 31.8 +/- 0.8, 47.4 +/- 0.3 and 61.7 +/- 1.5 W in vivo. For the
      same power readout, the ex vivo or in vivo effective power was the same (P =
      0.841, P = 0.133, P = 0.551). For both ex vivo and in vivo experiments, the ratio
      of microwave antenna energy loss to microwave antenna input energy was relatively
      constant (P = 0.613, 0.326). For the same treatment time and net power, the
      difference was significant between ex vivo and in vivo ablation volumes (P =
      0.001, 0.006, 0.001). CONCLUSION: Using net power as a reference during MWA is
      more accurate compared to the traditional power readout. And net energy offers a
      more realistic reflection of MWA energy in tissues.

PMID- 23158725
TI  - Pyridocoumarin, aristolactam and aporphine alkaloids from the Australian
      rainforest plant Goniothalamus australis.
AB  - Chemical investigation of the CH(2)Cl(2)/CH(3)OH extracts from aerial parts of
      the Australian plant Goniothalamus australis has resulted in the isolation of two
      pyridocoumarin alkaloids, goniothalines A (1) and B (2) as well as eight known
      natural products, aristolactam AII (3), enterocarpam II (4), caldensine (5),
      sauristolactam (6), (-)-anonaine (7), asimilobine (8), altholactone (9) and (+)
      goniofufurone (10). The chemical structures of all compounds were determined by
      extensive spectroscopic and spectrometric analysis. Methylation of 2 using TMS
      diazomethane afforded 1, which unequivocally established that both 1 and 2
      possessed a 10-methyl-2H-pyrano[2,3-f]quinolin-2-one skeleton. These
      pyridocoumarin alkaloids are putatively proposed to arise biosynthetically from
      an aporphinoid precursor. Compounds 1-10 were evaluated for in vitro antimalarial
      activity against a chloroquine-sensitive Plasmodium falciparum line (3D7).
      Sauristolactam (6) and (-)-anonaine (7) exhibited the most potent antiparasitic
      activity with IC(50) values of 9 and 7 MUM, respectively.

PMID- 23158724
TI  - Subjective health complaints in older adolescents are related to perceived
      stress, anxiety and gender - a cross-sectional school study in Northern Sweden.
AB  - BACKGROUND: Negative trends in adolescent mental and subjective health are a
      challenge to public health work in Sweden and worldwide. Self-reported mental and
      subjective health complaints such as pain, sleeping problems, anxiety, and
      various stress-related problems seem to have increased over time among older
      adolescents, especially girls. The aim of this study has therefore been to
      investigate perceived stress, mental and subjective health complaints among older
      adolescents in Northern Sweden. METHODS: Data were derived from a cross-sectional
      school-based survey with a sample consisting of 16-18 year olds (n = 1027), boys
      and girls, in the first two years of upper secondary school, from different
      vocational and academic programmes in three public upper secondary schools in a
      university town in northern Sweden. Prevalence of perceived stress, subjective
      health complaints, general self-rated health, anxiety, and depression were
      measured using a questionnaire, including the Hospital Anxiety and Depression
      Scale (HADS). RESULTS: A large proportion of both girls and boys reported health
      complaints and perceived stress. There was a clear gender difference: two to
      three times as many girls as boys reported subjective health complaints, such as
      headache, tiredness and sleeping difficulties and musculoskeletal pain, as well
      as sadness and anxiety. High pressure and demands from school were experienced by
      63.6% of girls and 38.5% of boys. Perceived stress in the form of pressure and
      demands correlated strongly with reported health complaints (r = 0.71) and
      anxiety (r = 0.71). CONCLUSIONS: The results indicate that mental and subjective
      health complaints are prevalent during adolescence, especially in girls, and
      furthermore, that perceived stress and demands may be important explanatory
      factors. Future studies should pay attention to the balance between gender
      related demands, perceived control and social support, particularly in the school
      environment, in order to prevent negative strain and stress-related ill-health.
      The gender gap in subjective adolescent health needs to be further explored.

PMID- 23158726
TI  - A free geometry model-independent neural eye-gaze tracking system.
AB  - BACKGROUND: Eye Gaze Tracking Systems (EGTSs) estimate the Point Of Gaze (POG) of
      a user. In diagnostic applications EGTSs are used to study oculomotor
      characteristics and abnormalities, whereas in interactive applications EGTSs are
      proposed as input devices for human computer interfaces (HCI), e.g. to move a
      cursor on the screen when mouse control is not possible, such as in the case of
      assistive devices for people suffering from locked-in syndrome. If the user's
      head remains still and the cornea rotates around its fixed centre, the pupil
      follows the eye in the images captured from one or more cameras, whereas the
      outer corneal reflection generated by an IR light source, i.e. glint, can be
      assumed as a fixed reference point. According to the so-called pupil centre
      corneal reflection method (PCCR), the POG can be thus estimated from the pupil
      glint vector. METHODS: A new model-independent EGTS based on the PCCR is
      proposed. The mapping function based on artificial neural networks allows to
      avoid any specific model assumption and approximation either for the user's eye
      physiology or for the system initial setup admitting a free geometry positioning
      for the user and the system components. The robustness of the proposed EGTS is
      proven by assessing its accuracy when tested on real data coming from: i)
      different healthy users; ii) different geometric settings of the camera and the
      light sources; iii) different protocols based on the observation of points on a
      calibration grid and halfway points of a test grid. RESULTS: The achieved
      accuracy is approximately 0.49 degrees , 0.41 degrees , and 0.62 degrees  for
      respectively the horizontal, vertical and radial error of the POG. CONCLUSIONS:
      The results prove the validity of the proposed approach as the proposed system
      performs better than EGTSs designed for HCI which, even if equipped with superior
      hardware, show accuracy values in the range 0.6 degrees -1 degrees .

PMID- 23158728
TI  - Determinant factors of gender identity: a commentary.
AB  - Paediatric specialists involved in the care of children with disorders of sex
      development may be expected to provide straightforward answers to questions
      concerning the "true sex" of a child, reflecting common perceptions of sex/gender
      as an immutable binary biological reality. This article highlights how much more
      broad and complex the topic of gender identity and its development is. Many
      theories have been put forward to advance knowledge of gender identity. Against
      the breadth and depth of this vast topic, the current overview is inevitably
      incomplete. It begins by arguing for a more consistent use of 'sex' and 'gender'.
      It considers in turn three influential theoretical frameworks that lend
      themselves to empirical research. These are: 1) the role of the brain; 2) the
      role of socialisation; and 3) multi-dimensional gender development. The article
      ends by suggesting potentially fruitful questions and areas for future research.

PMID- 23158729
TI  - [Pay attention to the adaptive immune regulation and relevant biological
      phenomena in gastrointestinal disorders].

PMID- 23158727
TI  - Multiple environmental chemical exposures to lead, mercury and polychlorinated
      biphenyls among childbearing-aged women (NHANES 1999-2004): Body burden and risk
      factors.
AB  - BACKGROUND: Lead, mercury and polychlorinated biphenyls (PCBs) are neurotoxicants
      with intergenerational health consequences from maternal body burden and
      gestational exposures. Little is known about multiple chemical exposures among
      childbearing-aged women. OBJECTIVES: To determine the percentage of women aged 16
      49 of diverse races and ethnicities whose body burdens for all three xenobiotics
      were at or above the median; to identify mixed exposures; and to describe those
      women disproportionately burdened by two or more of these chemicals based on
      susceptibility- and exposure-related attributes, socioeconomic factors and race
      ethnicity. METHODS: Secondary data analysis of National Health and Nutrition
      Examination Survey (1999-2004). RESULTS: The best-fit logistic regression model
      without interactions contained 12 variables. Four risk factors associated with
      body burden were notable (P<=0.05). An exponential relationship was demonstrated
      with increasing age. Any fish consumption in past 30 days more than doubled the
      odds. Heavy alcohol consumption increased the relative risk. History of
      breastfeeding reduced this risk. These women were more likely to have two
      xenobiotics at or above the median than one. More than one-fifth of these
      childbearing-aged women had three xenobiotic levels at or above the median.
      CONCLUSIONS: These findings are among the first description of US childbearing
      aged women's body burden and risk factors for multiple chemical exposures. This
      study supports increasing age, any fish consumption and heavy alcohol consumption
      as significant risk factors for body burden. History of breastfeeding lowered the
      body burden. Limited evidence was found of increased risk among minority women
      independent of other risk factors.

PMID- 23158730
TI  - [A 10-day sequential therapy for eradication of Helicobacter pylori infection in
      children].
AB  - OBJECTIVE: To evaluate the clinical effect of a 10-day sequential therapy which
      was made up of omeprazole, clarithromycin, amoxicillin-clavulanate and
      metronidazole for the eradication of Helicobacter pylori (Hp) infection in
      children. METHOD: A total of 214 children with abdominal pain, who were confirmed
      to have Hp infection through endoscopy, biopsy, and Hp culture. The 214 cases
      were randomly divided into four groups. A 10-day sequential therapy group
      accepted omeprazole 0.8 - 1.0 mg/(kg.d) plus amoxicillin-clavulanate 50 mg/(kg.d)
      for five days and omeprazole 0.8 - 1.0 mg/(kg.d), clarithromycin 20 mg/(kg.d) and
      metronidazole 20 mg/(kg.d) for the remaining five days. The 7-day triple therapy
      group, 10-day triple therapy group and 14-day triple therapy group received
      omeprazole 0.8 - 1.0 mg/(kg.d), amoxicillin-clavulanate 50 mg/(kg.d) and
      clarithromycin 20 mg/(kg.d) for 7 days,10 days,14 days, respectively. All drugs
      were given twice daily. All these patients received (13)C urea breath test ((13)C
      UBT) four weeks after the treatment. RESULT: Finally, 199 patients were followed
      up, and the total rate of loss to follow-up was 7.0% (15/214). Hp eradication
      rate was 85.2% and 90.2% in the 10-day sequential therapy group on intention to
      treat (ITT) and per protocol (PP) analyses, 66.0% and 71.4% in the 7-day triple
      therapy group on ITT and PP analyses; 60.0% and 67.3% in 10-day triple therapy
      group on ITT and PP analyses, and 78.8% and 82.0% in patients who received the 10
      day sequential regimen on ITT and PP analyses, respectively. By ITT analysis,
      there was significantly difference between the 10-day sequential therapy group
      and 7-day or 10-day triple therapy group (P < 0.05), while no significant
      difference was found between the 10-day sequential therapy group and 14-day
      triple therapy group (P > 0.05). The results of the ITT analysis and the PP
      analysis were the same. The four groups had neither significant difference in
      abdominal pain relief (P > 0.05) nor in incidence of adverse reactions (P >
      0.05). CONCLUSION: The 10-day sequential regimen was significantly more effective
      than both 7-day triple regimen and 10-day triple regimen, while had the same
      eradication rate compared with the 14-day sequential therapy. But 10-day triple
      regimen to eradicate Hp infection in children had the advantages such as short
      course of treatment and better compliance.

PMID- 23158731
TI  - [Multi-disciplinary hybrid therapy for tracheoesophageal fistula in children:
      analysis of 4 cases].
AB  - OBJECTIVE: To explore an innovative technique that is aided by multi-disciplinary
      hybrid approach in identification and treatment of tracheoesophageal fistula
      (TEF) in children intraoperatively. METHOD: From April 2008 to October 2011, 4
      patients with isolated TEF were presented with 2 H-type fistulas and 2 recurrent
      TEF. For all the four cases, with the cooperation of the gastroenterologists,
      respiratory physician and surgeon, methylene blue was first injected into the
      trachea for detecting the dye in the esophagus by the gastroscopy. Bronchoscopy
      was performed where the fistula tract was shown by the methylene blue and a guide
      wire was passed through the fistula. The patients underwent rigid gastroscopy and
      the guide wire was identified and brought out through the mouth by biopsy pliers.
      This created a wire loop through the fistula. X-ray was then used to identify the
      level of the fistula. According to the level of the fistula it was determined
      whether surgical incision and approach should be used. The fistula was then
      repaired successfully by surgery. RESULT: In the 4 patients, with the aid of
      gastroscopy and bronchoscopy, identification of the fistula intraoperatively was
      then facilitated by traction on the loop. The fistula was identified and
      repaired. There were no fistula recurrences. CONCLUSION: Multi-disciplinary
      hybrid therapy for tracheoesophageal fistula in children is beneficial for the
      precise localization of the fistula. This new technique is an effective and
      definitive method in identification and treatment of TEF in children.

PMID- 23158732
TI  - [Congenital esophageal stenosis owing to ectopic tracheobronchial remnants:
      report of four cases and review of the literature].
AB  - OBJECTIVE: Congenital esophageal stenosis owing to tracheobronchial remnants
      (TBR) is a rare condition. This study was conducted to understand the clinical
      features of TBR. METHOD: The data of the four cases with TBR admitted to our
      hospital and 76 patients identified from the literature were reviewed. The
      clinical manifestation, X-ray, endoscopy, biopsy and treatment were studied
      retrospectively. RESULT: Of the total of 80 cases, 45 were male, 33 were female,
      and for 2 cases the gender was unknown. Symptoms of dysphagia and regurgitation
      developed at the age of 1-day to 12-month. Definitive treatment was carried out
      at the age of 1-month to 16-year. Twenty-seven patients had associated anomalies
      with esophageal atresia being the most prevalent. X-ray esophagography showed
      segmental stenosis at the distal third of the esophagus in all patients except
      three. An abrupt narrow segment at the lower esophagus with marked proximal
      dilatation was found in 32 cases. Esophagography of 12 cases showed distal
      esophageal stenosis with tapered narrowing. Esophagography of 20 cases showed
      flask-shaped shadow of distal esophageal stenosis and one patient showed linear
      projection of barium at the level of stenosis. Endoscopy found almost complete
      obstruction of the lower esophageal lumen without signs of the esophagitis or
      reflux. Esophagoscopic dilatation of the stenosis was attempted in 24 cases, but
      was ineffective, and 3 patients suffered esophageal perforation. Seventy-nine
      patients underwent resection of the stenotic segment. Histologic examination of
      the resected specimen showed cartilage, mucus glands, resembling bronchal tissue.
      Post-operative complication included anastomotic stenosis, anastomotic leakage,
      hiatal hernia, and gastroesophageal reflux. CONCLUSION: TBR should be suspected
      in patients who present with a typical history of dysphagia after ingestion of
      solid food. Esophagography and esophagoscopy are the essential means for
      diagnosis. TBR should be different from achalasia and should be diagnosed by
      biopsy. Operation is the only choice of treatment.

PMID- 23158733
TI  - [Fever-induced refractory epileptic encephalopathy in school-aged children:
      clinical features and outcome-a multicenter study on 13 children].
AB  - OBJECTIVE: To analyze the clinical features and outcomes of fever-induced
      refractory epileptic encephalopathy in school-aged children (FIRES) in China.
      METHOD: A retrospective multicenter study on 13 FIRES patients was conducted. By
      collecting the medical data and follow up research of these patients, the
      clinical manifestations, clinical courses, investigations, treatments and
      outcomes of FIRES patients were analyzed. RESULT: The 13 enrolled patients were
      previously healthy. The median age at onset was 8.3 years. The male-to-female
      ratio was 6:7. They exhibited with prolonged refractory status epilepticus after
      fever onset. All the patients presented with partial seizures, 9 of them had
      secondary generalized epilepsy; 12 patients had EEG data, 6 of them showed
      asymmetric diffused slow wave. Seven patients presented with focal or multifocal
      discharges mostly located in frontotemproal areas. n acute period, many seizures
      (up to 100) could occur each day. Between seizures, the patients were drowsy or
      even comatose. Neuroimaging demonstrated normal findings in 10 children.
      Classical anti-epileptic drugs (AED, 3-7 kinds, median 5) were ineffective; 3
      children received anesthesia treatment.Eight patients were admitted to ICU, 6 of
      them needed mechanical ventilation. One patient died 1 week after discharge. n
      follow up period, most patients were in a stable and chronic condition. Seizures
      were controlled by AED only in 1 child. Parents of 1 patient gave up all
      treatment but the patient still had seizure. Other 10 patients had refractory
      epilepsy that could not be controlled by 3-4 AEDs. We collected neuroimaging data
      of 11 patients in follow up period, 1 of the 9 previously normal patients
      exhibited temporal lobe atrophy, others did not show any change compared with
      that in acute phase. Only 3 of the 12 surviving patients retained normal
      cognitive level but all of them could not recover to pre-morbidity status.
      CONCLUSION: FIRES is a devastating epileptic encephalopathy with unknown cause.
      Different kinds of anti-epileptic treatments were given without satisfactory
      effect, even extensive treatment efforts including intensive care were
      unsuccessful. Thus the outcome is disastrous in most of the previously healthy
      children.

PMID- 23158734
TI  - [Phenotype and SCN1A gene mutation screening in 39 families with generalized
      epilepsy with febrile seizures plus].
AB  - OBJECTIVE: To summarize the phenotypes and identify SCN1A mutations in families
      with generalized epilepsy with febrile seizures plus (GEFS(+)), and analyze the
      genotype- phenotype correlations in GEFS(+) families. METHOD: Genomic DNA was
      extracted from peripheral blood lymphocytes of the proband and other available
      members in the GEFS(+) families. The phenotypes of the affected members were
      analyzed. The coding regions and flanking intronic regions of the SCN1A gene were
      screened for mutations using PCR and direct DNA sequencing. RESULT: In 39 GEFS(+)
      families, there were 196 affected members, ranging from 2 to 22 affected members
      in each family. Their phenotypes included febrile seizures (FS) in 92(46.9%),
      febrile seizures plus (FS(+)) in 62(31.6%), FS or FS(+) with partial seizures in
      12(6.1%), afebrile generalized tonic-clonic seizures (AGTCS) in 11(5.6%),
      myoclonic atonic epilepsy in 8(4.1%), Dravet syndrome in 2(1.0%), childhood
      absence epilepsy in 1 (0.5%), FS(+) with myoclonic seizures in 1(0.5%), AGTCS and
      myoclonic seizures in 1 (0.5%), partial seizures in 1 (0.5%), unclassified
      seizures in 5 (2.6%). Four families were found with SCN1A mutations, including
      three families with missense mutation (N935H, R101Q, G1382R) and one family with
      truncation mutation (C373fsx378). In three families with missense mutations, the
      phenotypes include FS, FS(+), FS(+) with partial seizures, and AGTCS. In one
      family with truncation mutation, the phenotypes included FS, FS(+), and Dravet
      syndrome. The mother of proband in the family with missense mutation (R101Q) and
      the father of proband in the family with truncation mutation (C373fsx378) were
      both somatic mosaicism. Both of their phenotypes were FS(+). CONCLUSION: The most
      common phenotypes of GEFS(+) were FS and FS(+), followed by the FS/FS(+) with
      partial seizures and AGTCS. The most severe phenotype was Dravet syndrome. SCN1A
      mutation rate in GEFS(+) was about 10%. Missense mutation was common in GEFS(+)
      families, few with truncation mutation. Few members of GEFS(+) families had
      somatic mosaicism of SCN1A mutations and their phenotypes were relatively mild.

PMID- 23158735
TI  - [Analysis of the prognosis and clinical factors in primary vesicoureteral reflux
      patients].
AB  - OBJECTIVE: To analyze the relationship between the prognosis and clinical factors
      of primary vesicoureteral reflux (VUR) patients under the condition of non
      surgical treatment. METHOD: The medical records of the patients who were
      diagnosed as VUR by micturating cystourethrography (MCU) from January 2000 to
      December 2009 in Children's Hospital of Fudan University underwent non-surgical
      treatment, and followed up for more than one year then had repeated MCU, were
      retrospectively reviewed. RESULT: A total of 73 children (30 boys, 43 girls) were
      included in this study. The percentage of mild reflux (grade I-II) was 19.2%
      (14/73), that of moderate reflux (grade III) was 53.4% (39/73), and that of
      severe reflux (grade IV-V) was 27.4% (20/73). Among 73 patients, 27 (37.0%)
      patients were found to have renal damage. The average interval of repeated MCU
      was (1.29 +/- 0.40) years (1 - 2 years). After follow-up, it was found that the
      reflux grade was relieved in 41 (56.2%) patients, of whom 27 (37.0%) patients
      achieved complete resolution, 32 (43.8%) patients did not have remission in
      reflux grade, of whom 13 (17.8%) patients had worsened reflux grade. Logistic
      regression analysis showed that VUR patients with renal damage at initial
      diagnosis was an important clinical factor to affect reflux remission (P =
      0.000), complete resolving (P = 0.008) and result in worsening (P = 0.002).
      CONCLUSION: A certain proportion of primary VUR patients could get reflux grade
      self-resolution, it was also quite common in severe VUR patients. VUR patients
      with renal damage at initial diagnosis was an important clinical factor affecting
      the reflux grade prognosis. Mild and moderate VUR patients with renal damage were
      at risk of worsening. VUR patients with high reflux grade had normal renal status
      could still get remission or even disappearance of VUR. But severe VUR patients
      with renal damage were still recommended to receive surgical therapy.

PMID- 23158736
TI  - [Clinical and laboratory features of pediatric acute myeloid leukemia with
      inversion of chromosome 16].
AB  - OBJECTIVE: To evaluate the clinical and laboratory features of pediatric inv(16)
      acute myeloid leukemia (AML) retrospectively. METHOD: Dual color fluorescence in
      situ hybridization (D-FISH) using a LSI CBFbeta inv(16) break apart probe labeled
      by Spectrum red and Spectrum green was performed in 15 acute myeloid leukemia
      cases, including 13 cases with or without abnormal eosinophils but with positive
      core binding factor beta (CBFbeta)-MYH11 fusion transcript detected by RT-PCR,
      and 2 cases with trisomy 8 (+8). The results were compared with the morphology,
      immunophenotype, karyotype and RT-PCR. RESULT: Morphologically, 12 cases were
      diagnosed as M(4)EO, 2 as M(4), and 1 as M(2a). Immunophenotypically, all 13 AML
      cases with inv(16) showed positive expression of CD(13) and CD(33), but without
      the expression of any lymphoid lineage antigens. Karyotyping analysis with G
      banding detected inv(16) in 10 AML cases, including 9 M(4)EO cases and 1 M(2a),
      but only 5 positive cases were detected using R-banding technique. Among them, 2
      cases had simultaneous +8 and trisomy22 (+22), one had +22 only in addition to
      inv(16). D-FISH revealed a CBFbeta-MYH11 rearrangement in 13 cases of AML with
      positive RT-PCR results, and the mean positive rate of cell detection was 55.15%
      (range 37.0% - 86.0%). The complete remission rate (CR) and median survival
      period in this series of inv(16) AML were 81.5%and 11 months, respectively, of
      whom, 8 cases were still in CR. Relapse and karyotypic evolution were seen in
      case 5 with +8, +22 in addition to inv(16). CONCLUSION: AML with inv(16) is a
      special subtype. Most cases belong to M(4)EO. Its prognosis is good in general,
      but it seems to be an unfavorable feature for AML with inv(16) and +8, +22
      simultaneously, especially with karyotypic evolution. For detection of inv(16), G
      banding technique is evidently superior to R-banding technique. D-FISH combined
      with RT-PCR are more sensitive and reliable than chromosome banding analysis.

PMID- 23158737
TI  - [Paraneoplastic neurological syndrome in 12 children].
AB  - OBJECTIVE: To investigate the basic clinical characteristics of paraneoplastic
      neurological syndrome (PNS) in children. METHOD: To retrospectively analyze the
      clinical data of 12 PNS children who were hospitalized in neurology department in
      Beijing Children's Hospital from 2010 to 2011. Some patients were followed up
      after surgery. RESULT: In 12 patients with PNS, 11 were male and 1 was female.
      The mean onset age were (30.5 +/- 15.3) months. The mean duration from
      neurological symptom onset to finding out of tumor was (112.7 +/- 154.4) days.
      The onset of the disease in 2 patients was acute, in 3 was subacute and in the
      other 7 was chronic (2 of 7 had 2 to 3 relapses). Of 12 patients, 11 had symptoms
      of ataxia (3 patients also had opsoclonus and myoclonus, OMS), 1 had weakness of
      limbs at onset and then had ataxia. Nine of 12 patients had surgery, and
      pathologic diagnosis was neuroblastoma and ganglioneuroma. Six patients were
      followed-up for 8 to 21 months. One patient had a little improvement and 5 almost
      recovered. CONCLUSION: The PNS children can have neurological symptoms only at
      the onset and there were no particular evidence of tumor. It is prone to
      misdiagnosis. The prognosis of PNS in children was poor.

PMID- 23158738
TI  - [Wolman disease with novel mutation of LIPA gene in a Chinese infant].
AB  - OBJECTIVE: To explore the clinical characteristics of Wolman disease and
      diagnostic methods using enzymatic and molecular analysis. METHOD: Lysosomal acid
      lipase activity was measured using 4-methylumbelliferyl oleate in the leukocytes
      of an infant suspected of Wolman disease and LIPA gene mutational analysis was
      performed by PCR and direct sequencing in the proband and his parents. After the
      diagnosis was confirmed, the clinical, biochemical, radiological and
      histopathological findings in this case of Wolman disease were retrospectively
      reviewed. RESULT: The sixteen-day-old boy was failing to thrive with progressive
      vomiting, abdominal distention and hepatosplenomegaly. Abdominal X-ray revealed
      adrenal calcifications which were confirmed on abdominal CT scan. Xanthomatosis
      were observed on enlarged liver, spleen and lymph nodes during abdominal surgery.
      Liver and lymph node biopsy showed foamy histiocytes. The lysosomal acid lipase
      activity in leukocytes was 3.5 nmol/(mg.h) [control 35.5 - 105.8 nmol/(mg.h)].
      Serum chitotriosidase activity was 315.8 nmol/(ml.h) [control 0 - 53
      nmol/(ml.h)]. The patient was homozygote for a novel insert mutation allele c.318
      ins T, p. Phe106fsX4 in exon 4 on LIPA gene. His both parents were carriers of
      the mutation. CONCLUSION: The clinical features of Wolman disease include early
      onset of vomiting, abdominal distention, growth failure, hepatosplenomegaly and
      bilateral adrenal calcification after birth. A plain abdominal X-ray film should
      be taken to check for the typical pattern of adrenal calcification in suspected
      cases of Wolman disease. The enzymatic and molecular analyses of lysosomal acid
      lipase can confirm the diagnosis of Wolman disease.

PMID- 23158739
TI  - [Cornelia de Lange syndrome: report of a case and the review of literature on 17
      cases].
AB  - OBJECTIVE: To explore the clinical characteristics of Cornelia de Lange Syndrome
      (CdLS) and to review the latest clinical research reports. METHOD: Clinical and
      laboratory data of one case of neonatal CdLS are reported, and literature on 17
      cases of CdLS in China and the international reports of the clinical and
      molecular biological research on this disease were reviewed. RESULT: (1) The
      patient was an infant with intrauterine growth retardation and born as a term
      small for gestational age infant with specific facial features, bone abnormality
      of extremities, and patent ductus arteriosus (PDA). She also had severe feeding
      difficulty and slow weight gain. She was followed up till 4 months of age and
      showed severe developmental retardation. (2) The total number of past reported
      case of CdLS in China was 17 with a male to female ratio of 6:12. The average age
      of diagnosis was 17 months. The following specific facial features could be
      observed: synophrys, long and curved eyelashes, hirsutism, microcephalus, low
      hairline, broad depressed nasal bridge, long prominent philtrum, and high palate.
      Most of the patients were complicated with mental retardation, recurrent vomiting
      or feeding difficulty, abnormal muscle tone, cutis marmorata, hypophalangism, and
      genitalia anomaly. Clinical manifestations of Chinese patients were similar to
      those of the overseas reports. The karyotype of 15 cases was investigated and was
      normal. The etiology of CdLS is unknown. There is no specific treatment. The
      commonest causes of death are lung diseases caused by gastroesophageal
      reflex/aspirate related pneumonia. CONCLUSION: Typical clinical manifestations of
      CdLS are specific facial features (mainly synophrys, long and curved eyelashes,
      long prominent philtrum), complications of multi-system malformations (mainly
      growth and developmental retardation, esophagogastric reflex, hypophalangism),
      related gene mutations occurred in NIPBL, SMC1A, and SMC3 gene.

PMID- 23158740
TI  - [Clinical analysis of early postoperative pulmonary infection in children after
      living donor liver transplantation].
AB  - OBJECTIVE: To analyze the condition of early (<= 30 d) postoperative pulmonary
      infection in children after living donor liver transplantation (LDLT). METHOD:
      The clinical data of 36 cases undergoing LDLT in Children's Hospital of Chongqing
      Medical University were analyzed retrospectively from June 2006 to December 2009.
      RESULT: Of 36 cases without preoperative respiratory disease, 17 were boys, 19
      were girls. Their age ranged from 2 months to 14 years. Pulmonary infection
      developed in 24 patients, of whom 4 cases died (17%) and 3 deaths were related to
      pulmonary infection. Pulmonary infection occurred in 17 of 20 infants (85%) and
      10 of 11 cases (91%) with liver function of Child-Pugh grade C. Twenty cases
      (83%) developed pulmonary infection within first 2 weeks after LDLT. Totally 65
      pathogenic strains of microorganisms were isolated, in which Gram-negative
      bacteria, Gram-positive bacteria and fungi were 46 strains, 5 strains, 14 strains
      respectively. The most frequently isolated bacteria were Pseudomonas aeruginosa
      (14 strains), Klebsiella pneumoniae (8 strains) and Acinetobacter baumannii (8
      strains). Pseudomonas aeruginosa showed a resistance rate of almost 100% to
      cotrimoxazole, tetracycline, chloramphenicol, ampicillin, the first, the second
      and some of the third generation cephalosporins. Klebsiella pneumoniae producing
      extended spectrum beta-lactamase had a resistance rate of almost 100% to beta
      lactams except carbapenems. Acinetobacter baumannii was exquisitely susceptible
      to carbapenems, but showed a high resistance to penicillins and cephalosporins.
      Candida albicans, which was the most common fungus, showed a susceptibility rate
      of 100% to amphotericin B. In the LDLT recipients of pulmonary infection,
      cytomegalovirus (CMV) infections occurred in 2 patients and Epstein Barr virus
      (EBV) infection in 1 patient. CONCLUSION: The incidence of early postoperative
      pulmonary infection was high in children undergoing LDLT, especially in infants.
      And the mortality should not be ignored. The high risk period for infection was
      within the first 2 weeks after operation. The pathogens were mainly Gram-negative
      bacteria, which showed high and multidrug resistance.

PMID- 23158741
TI  - [The recommendations on diagnosis and management of children with juvenile
      dermatomyositis].

PMID- 23158742
TI  - [Interpretation of "recommendation for diagnostic criteria for infectious
      endocarditis in children"].

PMID- 23158743
TI  - [Interpretation of "the recommendations on diagnosis and management of children
      with juvenile dermatomyositis"].

PMID- 23158744
TI  - [Kawasaki disease complicated with cerebral infarction: a case report].

PMID- 23158745
TI  - [Folic acid metabolism gene polymorphism and congenital heart disease].

PMID- 23158746
TI  - [Progress in studies on somatic mutations in congenital heart disease].

PMID- 23158747
TI  - [Status of joint and intracranial bleeding of moderate and severe hemophilia in
      children under on-demand therapy].

PMID- 23158748
TI  - Comprehensive analysis of the genome transcriptome and proteome landscapes of
      three tumor cell lines.
AB  - We here present a comparative genome, transcriptome and functional network
      analysis of three human cancer cell lines (A431, U251MG and U2OS), and
      investigate their relation to protein expression. Gene copy numbers significantly
      influenced corresponding transcript levels; their effect on protein levels was
      less pronounced. We focused on genes with altered mRNA and/or protein levels to
      identify those active in tumor maintenance. We provide comprehensive information
      for the three genomes and demonstrate the advantage of integrative analysis for
      identifying tumor-related genes amidst numerous background mutations by relating
      genomic variation to expression/protein abundance data and use gene networks to
      reveal implicated pathways. 

PMID- 23158749
TI  - Adiponectin, leptin and ghrelin levels in obese adolescent girls with polycystic
      ovary syndrome.
AB  - STUDY OBJECTIVE: To evaluate the differences in adipokines, namely adiponectin,
      leptin, and ghrelin, in obese adolescent girls with or without polycystic ovary
      syndrome (PCOS). DESIGN: Case-control study. SETTING: University hospital.
      PARTICIPANTS: 38 adolescent girls (age 15-20 years). Group I: 17 Obese adolescent
      girls with PCOS (BMI >= 30 kg/m(2)); Group II: Control group of 21 obese
      adolescent girls (BMI >= 30 kg/m(2)). MAIN OUTCOME MEASURES: Adiponectin, leptin,
      and ghrelin measurements. RESULTS: LH, LH/FSH, and cortisol levels were
      significantly higher in the obese PCOS girls compared to the obese controls (6.94
      +/- 3.28 vs 4.44 +/- 1.79; 1.50 +/- 0.72 vs 0.90 +/- 0.36; 16.02 +/- 4.28 vs
      12.46 +/- 5.29; P < .05, respectively). Adiponectin, leptin, and ghrelin levels
      were similar between the obese PCOS girls and the obese controls (11.13 +/- 6.00
      vs 15.26 +/- 12.66; 23.66 +/- 11.54 vs 23.11 +/- 11.17; 665.69 +/- 402.12 vs
      650.22 +/- 467.73, respectively). Adiponectin negatively correlated with BMI (r =
      -0.32; P = .04) and positively correlated with fasting glucose (r = 0.40; P =
      .01). Leptin positively correlated with BMI (r = 0.534; P = .001), estradiol (r =
      0.354; P = .02), and TSH (r = 0.374; P = .02). No significant correlation was
      found between ghrelin and the test parameters. CONCLUSION: Among obese
      adolescents with PCOS, adiponectin, and leptin levels do not seem to be
      determined by the existence of PCOS, while ghrelin presents no significant
      correlation.

PMID- 23158750
TI  - Abnormal vaginal pH and Mycoplasma genitalium infection.
AB  - STUDY OBJECTIVE: Mycoplasma genitalium (MG) is a sexually transmitted pathogen
      linked to female morbidity, but testing for MG is not standardized. We aimed to
      determine which point-of-care (POC) vaginal tests could predict MG infection.
      DESIGN, SETTING, PARTICIPANTS: A cross sectional study recruited sexually active
      adolescent women, aged 14-22 y (n = 217) from an urban medical center.
      INTERVENTIONS AND MAIN OUTCOME MEASURES: Vaginal swabs were POC tested for pH,
      amines, clue cells, sialidase, and Trichomonas vaginalis (TV). MG was detected by
      research-use-only transcription mediated amplification (TMA) assay. Presence of
      Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) were confirmed using
      TMA. Three criteria were required for diagnosis of clinical BV: pH > 4.5,
      presence of amines, and >20% clue cells. Associations were assessed using
      logistic regression (LR). RESULTS: TMA detected MG in 30 (14%), CT in 49 (23%),
      and NG in 21 (10%) of the samples tested. POC vaginal tests were positive for TV
      in 21%, amines in 52%, clue cells in 33%, sialidase in 22%, pH > 4.5 in 56%, and
      clinical BV in 19% of the samples tested. Using LR, pH > 4.5 was a predictor of
      MG (odds ratio 4.4, P < .05). Of 131 women without clinical BV or TV, 25% of
      those with pH > 4.5 had MG, compared to 9% of those with pH <= 4.5 (P = .02).
      CONCLUSIONS: Until standardized, approved testing for MG is available, pH may be
      a useful indicator to suspect MG, especially in the absence of BV and TV.

PMID- 23158751
TI  - Update on key topics in adolescent gynecology.
AB  - AM:STARs, the Adolescent Medicine State of the Art Reviews series published by
      the American Academy of Pediatrics, devoted its April 2012 issue to the topic of
      Adolescent Gynecology. Developed in conjunction with the North American Society
      for Pediatric and Adolescent Gynecology (NASPAG), the issue consists of twelve
      articles, written mostly by members of NASPAG. As editors of the issue, we
      present in this review for the Journal of Pediatric and Adolescent Gynecology
      (JPAG) a synopsis of the most salient concepts presented in those 12 articles.
      This review of reviews is intended to be an update on the "state of the art" in
      adolescent gynecology.

PMID- 23158752
TI  - Robotic assisted surgery in pediatric gynecology: promising innovation in mini
      invasive surgical procedures.
AB  - STUDY OBJECTIVE: Robotic assisted surgery is not yet widely applied in the
      pediatric field. We report our initial experience regarding the feasibility,
      safety, benefits, and limitations of robot-assisted surgery in pediatric
      gynecological patients. DESIGN: Descriptive, retrospective report of experience
      with pediatric gynecological patients over a period of 12 months. SETTING:
      Department of Pediatric Surgery, IRCCS Policlinico San Matteo Foundation.
      PARTICIPANTS: Children and adolescents, with a surgical diagnosis of ovarian
      and/or tubal lesions. MAIN OUTCOME MEASURES: Robot assembly time and operative
      time, days of hospitalization, time to cessation of pain medication, complication
      rate, conversion rate to laparoscopic procedure and trocar insertion strategy.
      RESULTS: Six children and adolescents (2.4-15 yrs), weighing 12-55 kg, underwent
      robotic assisted surgery for adnexal pathologies: 2 for ovarian cystectomy, 2 for
      oophorectomy, 1 for right oophorectomy and left salpingo-oophorectomy for gonadal
      disgenesis, 1 for exploration for suspected pelvic malformation. Mean operative
      time was 117.5 +/- 34.9 minutes. Conversion to laparatomy was not necessary in
      any of the cases. No intra- or postoperative complications occurred. CONCLUSION:
      Initial results indicate that robotic assisted surgery is safely applicable in
      the pediatric gynecological population, although it is still premature to
      conclude that it provides better clinical outcomes than traditional laparoscopic
      surgery. Randomized, prospective, comparative studies will help characterize the
      advantages and disadvantages of this new technology in pediatric patients.

PMID- 23158753
TI  - Clusters of markers identify high and low prevalence of adolescent pregnancy in
      the US.
AB  - STUDY OBJECTIVE: To identify markers that, when clustered, are associated with
      the highest and lowest pregnancy prevalence among US adolescent females. DESIGN:
      Secondary database analysis of the National Survey of Family Growth.
      PARTICIPANTS: Adolescent females 15-19 years old. SETTING: United States.
      METHODS: Bivariate analyses were performed of the 2002 and 2006-08 cycles to
      identify markers associated with pregnancy in females 15-19 years old. Recursive
      partitioning analysis (RPA) was done to identify markers which, when combined,
      identify adolescent females with the highest and lowest pregnancy prevalence.
      RESULTS: Pregnancy prevalence in 2,528 adolescent females was 14%. In RPA,
      females who ever HIV tested had a 48% pregnancy prevalence vs 4% in those never
      tested. The highest pregnancy prevalence (78%) was associated with the
      combination of ever HIV tested, never lived away from parents before 18 years
      old, age >17 years old, and age of sexual debut <=14 years old. Adolescent
      females with a combination of ever HIV tested, never lived away from parents
      before 18 years old, age >17 years old, age of sexual debut at 15-16 years old,
      and the adolescent's father not having a high-school diploma had a pregnancy
      prevalence of 75%. CONCLUSIONS: Two clusters of markers yield adolescent females
      with a very high adolescent pregnancy prevalence, at 75%-78%. Pregnancy
      prevention efforts might be especially effective when targeting combinations of
      HIV-testing history, never living away from home before 18 years old, adolescent
      age, age of sexual debut, and paternal educational attainment.

PMID- 23158754
TI  - Early pubertal development and insulin sensitivity among school-aged girls:
      mediation via adiposity.
AB  - STUDY OBJECTIVE: To examine whether the known association between early pubertal
      breast maturation and insulin sensitivity (SI) is mediated by adiposity. DESIGN:
      Cross-sectional analyses. SETTING: Observational study examining the roles of
      environment, diet, and obesity on puberty. PARTICIPANTS: 379 girls with a mean
      age, 7.03 years; 62% were white and 29% black. MAIN OUTCOME MEASURES: Pubertal
      development was assessed via physical examination and adiposity by body mass
      index Z score (BMI Z) and waist-to-height ratio. Fasting blood samples were
      obtained for insulin and glucose concentrations. SI was calculated with the
      quantitative insulin sensitivity check index (QUICKI). Analysis of variance and
      Sobel's test was used to assess mediation. RESULTS: Fifty-five girls were
      pubertal (Tanner 2 breast). Breast maturation was inversely associated with SI (P
      = .005) and positively associated with BMI Z (P < .001) and waist-to-height ratio
      (P < .001). The effect of breast maturation on SI was no longer significant (P =
      .41) after adjusting for the effect of BMI Z, which remained significant (P <
      .001). Similar results were obtained when waist-to-height ratio replaced BMI Z in
      the models. Mediation analyses demonstrated that 75% of the association between
      breast maturation and SI is mediated by adiposity. CONCLUSIONS: In girls,
      decreased SI during early puberty is largely mediated by total and visceral
      adiposity.

PMID- 23158755
TI  - Menstrual suppression in the adolescent.
AB  - Menstrual suppression, the use of contraceptive methods to eliminate or decrease
      the frequency of menses, is often prescribed for adolescents to treat menstrual
      disorders or to accommodate patient preference. For young women using hormonal
      contraceptives, there is no medical indication for menstruation to occur monthly,
      and various hormonal contraceptives can be used to decrease the frequency of
      menstruation with different side effect profiles and rates of amenorrhea. This
      article reviews the different modalities for menstrual suppression, common
      conditions in adolescents which may improve with menstrual suppression, and
      strategies for managing common side effects.

PMID- 23158756
TI  - Surgical treatment of the solid breast masses in female adolescents.
AB  - STUDY OBJECTIVE: To evaluate the histopathologic results of the excised solid
      breast masses in our clinic and to draw attention to breast masses in
      adolescents. DESIGN: A retrospective chart review study and review of the
      literature. SETTING: This study was conducted in Baskent University Adana
      Research Center between March 2003 and May 2011. PARTICIPANTS: Patients included
      10 adolescent girls admitted to pediatric surgery clinic with the complaint of
      palpable breast mass who underwent surgical excision of the breast mass. MAIN
      OUTCOME MEASURES: The necessity of surgery in breast masses of female
      adolescents. RESULTS: 10 female patients with an average age of 14 years were
      operated on for breast masses. A palpable mass in the breast and social anxiety
      were the cardinal complaints. Two patients had a family history of breast
      carcinoma. One patient had a history of neuroblastoma in remission.
      Histopathologic examination revealed 3 juvenile fibroadenomas, 1 conventional
      fibroadenoma, 3 tubular adenomas, and 3 phyllodes tumors. CONCLUSIONS: Palpable
      breast masses in adolescents are uncommon and are usually benign. The low
      malignancy risk and rarity of breast masses in childhood create a controversy as
      how to manage breast masses. Ultrasonography is the initial imaging modality to
      define the characteristics of the breast mass. Excisional biopsy and
      histopathologic examination is essential to rule out rare, but probable
      malignant, lesions in adolescents in selected patients such as maternal history
      of breast carcinoma, previous malignancy history in the patient, big size of the
      mass, and no regression on follow-up.

PMID- 23158757
TI  - Tubal endometrioma within a twisted fallopian tube: a clinically complex
      diagnosis.
AB  - BACKGROUND: Endometriotic lesions affect the fallopian tubes in 6% of patients
      with endometriosis and adhesions involve the salpinges in 26%. Different studies
      report that 45%-70% of adolescents with chronic pelvic pain have endometriosis
      diagnosed at the time of laparoscopy. CASE: We report a case of an 18-year-old
      girl with a tubal torsion due to a tubal endometrioma. The endometriotic nodule
      before laparoscopy appeared to be located in the rectovaginal septum. At
      laparoscopy, a right fallopian tube torsion was visible and several adhesions
      were connecting the lesion to the pouch of Douglas' walls. SUMMARY AND
      CONCLUSION: The tenacious adhesions, which welded the nodule to the walls of the
      pouch of Douglas, did not allow to distinguish at the MRI a tubal endometrioma
      from a rectovaginal endometriotic mass, justifying the false diagnosis.

PMID- 23158758
TI  - Independent versus substance-induced major depressive disorders in first
      admission patients with substance use disorders: an exploratory study.
AB  - BACKGROUND: Clinical differences between independent and substance-induced (S-I)
      major depressive disorders (MDDs) in patients with substance use disorders (SUDs)
      are insufficiently studied. METHODS: The catchment area sample consisted of 42
      SUD patients with independent and/or S-I MDD (bipolar disorders excluded),
      admitted consecutively to addiction clinics or psychiatry departments (inpatient
      or outpatient) with no previous treatment history from specialized services.
      Assessments included the Psychiatric Research Interview for Substance and Mental
      Disorders (PRISM), the Structured Clinical Interview for DSM-IV, Axis II,
      Personality Disorders (SCID-II), the Inventory of Depressive Symptoms (IDS), the
      Montgomery-Asberg Depression Rating Scale (MADRS), and the Symptom Check List, 90
      questions, revised (SCL-90-R). RESULTS: Of the 42 SUD patients, 48% had
      independent MDD episode(s) only, 24% had S-I MDD episode(s) only, and 28% had
      both independent and S-I MDD episodes. Insomnia, psychomotor agitation,
      concentration and decision problems, melancholic features, higher total MDD
      symptom count, longer time being depressed, higher mean score on the Montgomery
      Asberg Depression Rating Scale, and shorter duration of SUDs characterized
      independent MDDs. LIMITATIONS: Small sample size with risk of type II error.
      CONCLUSIONS: Independent MDDs were more severe and had different qualities
      compared with S-I MDDs, suggesting important treatment implications. Longitudinal
      studies including larger samples and carefully addressing the association between
      SUD subtypes and MDD subtypes are needed to substantiate our findings.

PMID- 23158759
TI  - Relationship of neuroticism and laboratory pain in healthy children: does anxiety
      sensitivity play a role?
AB  - Both neuroticism, a higher-order, stable personality trait, and anxiety
      sensitivity (AS), a lower-order pain-related construct, have been associated with
      pain, although no research exists examining the relationship of both these
      constructs to acute pain in children. In the current study, 99 healthy children
      (53 girls) completed self-report measures of neuroticism and AS before undergoing
      pain tasks involving cold and pressure pain. We hypothesized that both
      neuroticism and AS would be correlated with acute pain responses, but that AS
      would at least partially mediate the relationship between neuroticism and pain
      responses. Results indicated significant correlations between neuroticism, AS,
      and anticipatory anxiety, pain intensity and pain bother. Mediational models
      revealed that AS partially mediated relationships between neuroticism and pain
      intensity/bother, and fully mediated relationships between neuroticism and
      anticipatory anxiety. These data suggest that, at least in children, neuroticism
      may be best understood as a vulnerability factor for elevated pain responses,
      especially when coupled with a fear of bodily sensations.

PMID- 23158760
TI  - Accumulation profile and seasonal variations of polychlorinated biphenyls (PCBs)
      in bivalves Crassostrea tulipa (oysters) and Anadara senilis (mussels) at three
      different aquatic habitats in two seasons in Ghana.
AB  - Research has shown that some polychlorinated biphenyl congeners degrade slowly in
      the environment and build up in the food chain, causing a wide range of possible
      adverse effects to humans. In order to ascertain the nature of the situation in
      Ghana, polychlorinated biphenyls congener residues in Crassostrea tulipa
      (oysters) and Anadara senilis (mussels) at Narkwa, Ada and Anyanui in the coastal
      region of Ghana were determined. At Narkwa, both bivalves' species were
      collected; at Ada only Anadara senilis were collected while at Anyanui, only
      Crassotrea tulipa were collected. The number of each bivalve species collected
      from each site was 80 (n=80), making up a total of 320 for the dry and the wet
      seasons. The PCBs were extracted with (1:1) hexane-acetone mixture and analyzed
      with a gas chromatogram equipped with (65)Ni electron capture detector, model CP
      3800 using the mixed PCBs standard of the ICES 7. Total PCBs in the bivalves
      ranged from 5.55 to 6.37 MUg/kg wet weight in mussels and 2.95-11.41 MUg/kg wet
      weight in oysters, respectively. The composition of the PCB homologues in the
      bivalves was dominated by tri-, hepta- and hexa-PCBs in descending order. Risk
      assessments conducted on the samples indicated that edible bivalves from Narkwa,
      Ada and Anyanui in Ghana might pose some health risk to the consumers.

PMID- 23158762
TI  - Effects of memantine and galantamine on cognitive performance in aged rhesus
      macaques.
AB  - Current pharmacotherapies for Alzheimer's disease (AD) are focused on improving
      performance of daily activities, personal care, and management of problematic
      behaviors. Both memantine, a noncompetitive N-methyl-D-aspartate channel blocker
      and galantamine, a selective acetylcholinesterase inhibitor, are currently
      prescribed as symptomatic therapies for AD. However, drugs that progressed
      directly from testing in rodent models to testing in AD patients in clinical
      trials failed to demonstrate consistent effects on cognitive symptoms.
      Considering the lack of nonhuman primate data on the effects of memantine and
      galantamine alone or in combination on cognitive dysfunction in aged nonhuman
      primates, the present study examined how closely data derived from aged nonhuman
      primates reflects data obtained in humans. Mild beneficial effects on aspects of
      cognitive performance in aged primates were found, in general agreement with the
      human clinical experience with these drugs but in contrast to the more positive
      effects reported in the rodent literature. These data suggest that the nonhuman
      primate might have more predictive validity for drug development in this area
      than comparable rodent assays.

PMID- 23158761
TI  - Lower cognitive reserve in the aging human immunodeficiency virus-infected brain.
AB  - More HIV-infected individuals are living longer; however, how their brain
      function is affected by aging is not well understood. One hundred twenty-two men
      (56 seronegative control [SN] subjects, 37 HIV subjects with normal cognition
      [HIV+NC], 29 with HIV-associated neurocognitive disorder [HAND]) performed
      neuropsychological tests and had acceptable functional magnetic resonance imaging
      scans at 3 Tesla during tasks with increasing attentional load. With older age,
      SN and HIV+NC subjects showed increased activation in the left posterior
      (reserve, "bottom-up") attention network for low attentional-load tasks, and
      further increased activation in the left posterior and anterior ("top-down")
      attention network on intermediate (HIV+NC only) and high attentional-load tasks.
      HAND subjects had only age-dependent decreases in activation. Age-dependent
      changes in brain activation differed between the 3 groups, primarily in the left
      frontal regions (despite similar brain atrophy). HIV and aging act
      synergistically or interactively to exacerbate brain activation abnormalities in
      different brain regions, suggestive of a neuroadaptive mechanism in the attention
      network to compensate for declined neural efficiency. While the SN and HIV+NC
      subjects compensated for their declining attention with age by using reserve and
      "top-down" attentional networks, older HAND subjects were unable to compensate
      which resulted in cognitive decline.

PMID- 23158763
TI  - Spatial behavior and seizure-induced changes in c-fos mRNA expression in young
      and old rats.
AB  - The subcellular processes of gene induction and expression in the hippocampus are
      likely to underlie some of the known age-related impairments in spatial learning
      and memory. It is well established that immediate-early genes are rapidly and
      transiently induced in response to neuronal activity and this expression is
      required for stabilization of durable memories. To examine whether age-related
      memory impairment might be caused, in part, by differences in the level of
      cellular activation or subcellular processing, c-fos expression in CA1 pyramidal
      and dentate gyrus granule cells in the dorsal hippocampus of young and old rats
      was determined using fluorescence in situ hybridization and reverse transcription
      polymerase chain reaction. No significant age differences were found in the
      numbers of pyramidal or granule cells that show c-fos expression; however, c-fos
      mRNA transcripts were altered in these 2 cell types in aged animals. These
      findings suggest that though the networks of cells that participate in behavior
      or seizure-induced activity are largely maintained in aged rats, their RNA
      transcript levels are altered. This might, in part, contribute to cognitive
      deficits frequently observed with advancing age.

PMID- 23158766
TI  - Mental health services for black and minority ethnic elders in the United
      Kingdom: a systematic review of innovative practice with service provision and
      policy implications.
AB  - BACKGROUND: The proportion of older people from black and minority ethnic (BME)
      groups in the United Kingdom (UK) is increasing steadily as the population ages.
      The numbers with dementia, depression, and other mental health problems are
      predicted to increase. Government policy documents have highlighted gaps in
      services for BME elders and/or the need to develop culturally appropriate
      services, in order to prevent people from BME communities from becoming socially
      excluded and finding services hard to access. This paper reviews published
      examples of innovative services and key learning points from them. METHOD: A
      search was carried out on Pubmed, Medline, and Google Scholar for service
      developments aimed at BME elders in the UK. Sixteen relevant papers and reports
      were identified and were analysed to identify learning points and implications
      for clinical practice and policy. RESULTS: Commissioning issues included were
      forward planning for continuing funding and mainstreaming versus specialist
      services. Provider management issues included were employing staff from the
      communities of interest, partnership, and removing language barriers. Provider
      service issues included were education for service provider staff on the needs of
      BME elders, making available information in relevant languages, building on
      carers' and users' experiences, and addressing the needs of both groups.
      CONCLUSION: A model for structuring understanding of the underutilisation of
      services by BME elders is suggested. The main emphasis in future should be to
      ensure that learning is shared, disseminated, and applied to the benefit of all
      communities across the whole of the UK and elsewhere. Person-centred care is
      beneficial to all service users.

PMID- 23158765
TI  - Cascade of tau toxicity in inducible hippocampal brain slices and prevention by
      aggregation inhibitors.
AB  - Mislocalization and aggregation of the axonal protein tau are hallmarks of
      Alzheimer's disease and other tauopathies. Here, we studied the relationship
      between tau aggregation, loss of spines and neurons, and reversibility by
      aggregation inhibitors. To this end we established an in vitro model of tauopathy
      based on regulatable transgenic hippocampal organotypic slice cultures prepared
      from mice expressing proaggregant Tau repeat domain with mutation DeltaK280
      (Tau(RD)DeltaK). Transgene expression was monitored by a bioluminescence reporter
      assay. We observed abnormal tau phosphorylation and mislocalization of exogenous
      and endogenous tau into the somatodendritic compartment. This was paralleled by a
      reduction of dendritic spines, altered dendritic spine morphology, dysregulation
      of Ca(++) dynamics and elevated activation of microglia. Neurotoxicity was
      mediated by Caspase-3 activation and correlated with the expression level of
      proaggregant Tau(RD)DeltaK. Finally, tau aggregates appeared in areas CA1 and CA3
      after three weeks in vitro. Neurodegeneration was relieved by aggregation
      inhibitors or by switching off transgene expression. Thus the slice culture model
      is suitable for monitoring the development of tauopathy and the therapeutic
      benefit of antiaggregation drugs.

PMID- 23158764
TI  - Longitudinal measures of cholinergic forebrain atrophy in the transition from
      healthy aging to Alzheimer's disease.
AB  - Recent evidence from cross-sectional in vivo imaging studies suggests that
      atrophy of the cholinergic basal forebrain (BF) in Alzheimer's disease (AD) can
      be distinguished from normal age-related degeneration even at predementia stages
      of the disease. Longitudinal study designs are needed to specify the dynamics of
      BF degeneration in the transition from normal aging to AD. We applied recently
      developed techniques for in vivo volumetry of the BF to serial magnetic resonance
      imaging scans of 82 initially healthy elderly individuals (60-93 years) and 50
      patients with very mild AD (Clinical Dementia Rating score = 0.5) that were
      clinically followed over an average of 3 +/- 1.5 years. BF atrophy rates were
      found to be significantly higher than rates of global brain shrinkage even in
      cognitively stable healthy elderly individuals. Compared with healthy control
      subjects, very mild AD patients showed reduced BF volumes at baseline and
      increased volume loss over time. Atrophy of the BF was more pronounced in
      progressive patients compared with those that remained stable. The cholinergic BF
      undergoes disproportionate degeneration in the aging process, which is further
      increased by the presence of AD.

PMID- 23158767
TI  - Validation of the Orofacial Esthetic Scale in the general population.
AB  - BACKGROUND: The Orofacial Esthetic Scale (OES) is an eight-item instrument to
      assess how patients perceive their dental and facial esthetics. In this cross
      sectional study we investigated dimensionality, reliability, and validity of OES
      scores in the adult general population in Sweden. METHODS: In a random sample of
      the adult Swedish population (response rate: 39%, N=1159 subjects, 58% female,
      mean age (standard deviation): 49.2 (17.4) years), dimensionality of OES was
      investigated using factor analytic methods to determine how many scores are
      needed to characterize the construct. Reliability of scores was calculated using
      Cronbach's alpha. Score validity was determined by correlating the OES summary
      score with a global indicator of orofacial esthetics (OE). RESULTS: Factor
      analyses provided support that a single score can sufficiently characterize OE. A
      Cronbach's alpha of 0.93 indicated excellent reliability. A validity coefficient
      of r=0.89 (95% confidence interval: 0.87-0.90) indicated that OES summary scores
      correlated highly with a global OE assessment. CONCLUSIONS: The OES is a
      promising instrument to measure the construct OE. Factor analyses supported that
      this construct can be assessed with one score, offering a feasible and acceptable
      standardized assessment of OE. The present study extends the OES use to the
      general population, an important target population for assessment of orofacial
      esthetics.

PMID- 23158769
TI  - LARCs: a safe choice for teens with chronic medical conditions.

PMID- 23158770
TI  - Menstrual patterns and gynecologic morbidity among university students in Kano,
      Nigeria.
AB  - OBJECTIVE: To examine menstrual patterns and effects of menstrual disorders on
      social and academic lives of undergraduate students in Kano, Nigeria.
      PARTICIPANTS: Students attending Bayero University Kano, Nigeria (n = 383).
      INTERVENTION: Self-administered questionnaires. MAIN OUTCOME MEASURES:
      Sociodemographic characteristics, menstrual patterns, and associated symptoms
      were elicited. Treatment-seeking behavior and effects of symptoms on academic and
      social activities were ascertained. RESULTS: The mean age at menarche was 13.7 +/
      1.68 years. Menstrual bleeding lasted an average of 5.2 +/- 1.6 days. Cycle
      length was 21-35 days in 92% of cases (n = 353). Approximately 72% of respondents
      reported dysmenorrhea. After adjusting for confounding, age at menarche,
      menstrual cycle length, duration of menstrual bleeding and use of contraceptive
      pills remained significant predictors of dysmenorrhea. Menstrual disorders
      interfered with social and academic life of 91% and 84% of respondents
      respectively. CONCLUSIONS: Gynecologic morbidity related to menstruation is
      common among adolescent Nigerians and is associated with detrimental effects on
      academic and social activities. Student health services should prioritize
      measures to mitigate the social and physical impact of menstrual disorders in
      young women.

PMID- 23158771
TI  - Imiquimod 5% cream treatment for rapidly progressive genital condyloma in a 3
      year-old girl.
AB  - BACKGROUND: The incidence of genital warts in children has increased in the last
      50 years. Although pediatric genital warts may resolve spontaneously, the
      treatment of extensive perianal genital warts in children can be challenging.
      Imiquimod, although not approved in the pediatric population, may avoid the pain
      or extensive scarring associated with other treatment modalities. CASE: A 3-year
      old female was scheduled for surgical resection of genital warts. At surgery, she
      had extensive condylomas that had progressed rapidly from initial presentation.
      They were not amenable to surgical treatment due to concerns of incomplete
      resection, post-operative pain, and genital scarring. After 6 weeks of imiquimod
      treatment, the condylomatous lesions had completely resolved with minimal side
      effects. SUMMARY AND CONCLUSION: Imiquimod 5% cream is an effective treatment
      option for children with extensive and rapidly progressive perianal warts and is
      associated with minimal side effects. Its use should be considered in children
      with extensive condyloma in order to avoid the pain and possible scarring
      associated with other approved treatment modalities.

PMID- 23158772
TI  - An unusual presentation of uterine didelphys and obstructed hemivagina.
AB  - BACKGROUND: Congenital disorders of the genitourinary system can be
      unpredictable. There are both medical and surgical interventions that can help
      manage symptoms. CASE: A 10-year-old girl was evaluated 6 months post-menarche
      with dysuria and pelvic pain. Her symptoms were not relieved with menstrual
      suppression. Evaluation revealed a probable ectopic ureter versus ureterocele and
      uterine didelphys with suspicion for obstructed hemivagina and hematocolpos.
      Surgical exploration revealed an obstructed hemivagina with a high vaginal
      septum. When resection failed, she ultimately underwent a robot-assisted
      hemihysterectomy, with resolution of her symptoms. SUMMARY AND CONCLUSIONS: In
      this case presentation, a surgical approach was necessary to adequately make a
      diagnosis. When vaginal septum resection failed, robot-assisted laparoscopic hemi
      hysterectomy and resection of a vaginal pouch led to symptom resolution in this
      pediatric patient with a complex anomaly.

PMID- 23158773
TI  - Poor uptake of community based sexually transmissible infection testing at an
      inner city needle and syringe program.
AB  - Sydney Sexual Health Centre (SSHC) and the NSW Users and AIDS Association (NUAA),
      the NSW peer-based drug user organisation, pilot tested an outreach sexually
      transmissible infection (STI) testing station using self-collected urine and
      swabs in NUAA's needle and syringe program (NSP) space. The model was based on
      SSHC's established Xpress clinic. A needs assessment among NUAA clients was
      undertaken prior to commencement in order to ascertain potential uptake. A
      computer-assisted self interview was developed with data securely transferred to
      SSHC daily. During the 6 months from January to July 2011, almost 3000 occasions
      of service were recorded in the NSP from an estimated 375 clients. Four clients
      took advantage of NUAA Xpress during this time. Despite initial client interest,
      promotional efforts and the success of this methodology elsewhere, this outreach
      model did not have a successful uptake and was discontinued. This project
      provides value in considering the methodology and implementation of future
      outreach STI testing projects for people who inject drugs.

PMID- 23158774
TI  - Stronger together--the Epilepsy Therapy Project and Epilepsy Foundation decide to
      merge. Our personal stories and reflections.

PMID- 23158775
TI  - Health-related quality of life in Russian adults with epilepsy: the effect of
      socio-demographic and clinical factors.
AB  - OBJECTIVE: The aim of this study was to evaluate socio-demographic and clinical
      factors influencing the health-related quality of life (HRQOL) of adult patients
      with epilepsy in a naturalistic treatment setting in Russia. METHODS: The QOLIE
      31 questionnaire and the Beck Depression Inventory (BDI) were completed by 208
      patients with a broad clinical spectrum of epilepsy (the mean age was 31.49+/
      13.20 years and ranged from 18 to 74 years). RESULTS: In Russian adult patients
      with epilepsy, lower mean QOLIE-31 scores were obtained compared with previously
      published international data for overall HRQOL, emotional well-being, and
      cognitive functioning and social functioning subscales (p<0.001). Univariate
      analysis revealed that duration of epilepsy negatively correlated with all QOLIE
      31 subscores (p<0.05), except for emotional well-being (p=0.1). In multivariate
      regression analysis, BDI depression score was the predictor of overall score and
      all QOLIE-31 domains, except for emotional well-being. Age could be considered as
      a predictor of cognitive and social functioning, medical effects, and the total
      QOLIE -31 score. Seizure frequency was a factor associated with all HRQOL
      domains, except for medication effects and emotional well-being, whereas gender,
      education, family status, seizure type, employment, lateralization of epileptic
      foci, number of antiepileptic drugs, and the reported adverse events did not
      significantly affect HRQOL. CONCLUSION: The present study has revealed that
      longer duration of epilepsy, older age, higher seizure frequency, and depression
      are the potential predictors of worse HRQOL in adult Russian patients with
      epilepsy.

PMID- 23158776
TI  - Hippocampal volume reduction and autobiographical memory deficits in chronic
      schizophrenia.
AB  - Although autobiographical memory (AM) deficits and hippocampal changes are
      frequently found in schizophrenia, their actual association remained yet to be
      established. AM performance and hippocampal volume were examined in 33 older,
      chronic schizophrenic patients and 21 healthy volunteers matched for age, gender
      and education. Psychopathological symptoms and additional neuropsychological
      parameters were assessed by using appropriate rating scales; magnetic resonance
      imaging (MRI) 3-T data were analyzed via an automated region-of-interest
      procedure. When compared with the control subjects, patients showed significantly
      decreased left anterior and posterior hippocampal volumes. Episodic but not
      semantic AM performance was significantly lower in the patients than in the
      healthy controls. Both episodic and semantic AM deficits were significantly
      correlated with volume of the left hippocampus in the patient group. In contrast,
      deficits in verbal memory, working memory and remote semantic memory observed in
      the patients did not relate to hippocampal volume. Our findings indicate that AM
      deficits in chronic schizophrenia are associated with hippocampal volume
      reductions and underline the importance of this pathology in schizophrenia.

PMID- 23158777
TI  - Fronto-thalamic volumetry markers of somatic delusions and hallucinations in
      schizophrenia.
AB  - Although the psychotic phenomena of schizophrenia have been extensively
      investigated, somatic delusions and hallucinations have seldom been reported and
      their mechanisms are substantially unexplored. Here, we aimed to identify the
      brain structural correlates of somatic psychotic phenomena using combined
      volumetry and diffusivity structural neuroimaging techniques. Seventy-five
      individuals with a DSM-IV-TR diagnosis of schizophrenia and 75 healthy controls
      (HC) underwent a comprehensive clinical assessment, a high-resolution T1-weighted
      magnetic resonance imaging and a diffusion tensor imaging protocol using a 3T MRI
      scanner. Voxel-based volumetry and mean diffusivity (MD) of gray matter (GM) and
      fractional anisotropy (FA) of white matter (WM) of the whole brain were
      calculated for each subject. Reduced left fronto-insular GM volume was found in
      patients with somatic delusions compared with patients without somatic delusions
      and HC. Increased GM volume was found in the bilateral thalami, primarily in the
      right ventral-anterior thalamic nucleus projecting to the prefrontal-temporal
      cortices and the bilateral pars triangularis of the inferior frontal lobe, of
      patients with somatic hallucinations and HC compared with patients without
      somatic hallucinations. No differences emerged in GM MD and in WM FA between
      patients with and without psychotic somatic phenomena (i.e. delusions or
      hallucinations). These findings provide the first evidence that a frontal
      thalamic structural perturbation mediates somatic psychotic phenomena in
      schizophrenia.

PMID- 23158778
TI  - Preserved hippocampal function during learning in the context of risk in
      adolescent suicide attempt.
AB  - Impairment in decision-making is frequently observed in suicide attempters.
      Little is known, however, about neural circuitry underlying decision-making in
      adolescent attempters. Functional magnetic resonance imaging (fMRI) was used to
      assess decision-making and learning-related neural activity during Iowa Gambling
      Task (IGT) performance in adolescents with depression and suicide attempt (ATT,
      n=15), non-attempters with depression (NAT, n=14), and healthy controls (HC,
      n=13). ATT performed best on the IGT. A three group by two condition (high-risk
      versus low-risk) by three IGT block (each of 20 cards) whole-brain analysis
      (p<0.05, corrected) interaction was found in the left hippocampal, frontal and
      temporal cortical, striatal and thalamic regions. Post-hoc analyses revealed that
      during low-risk decisions in blocks 2 and 3, NAT, but not ATT, showed greater
      left hippocampal activation versus HC (p=0.0004, p=0.003); in block 2, during low
      risk decisions NAT showed greater left middle temporal gyral activation versus HC
      (p=0.003); in block 3, during high-risk decisions ATT showed less activation in
      the right thalamus versus NAT (p=0.001) and during low risk decisions ATT showed
      greater activation than HC in the left caudate (p=0.002). NAT, but not ATT are
      differentiated from HC during performance of the IGT. Functional abnormalities in
      neural circuitry implicated in learning in the context of risk may underlie risk
      for MDD, but not risk for suicide attempt, in adolescence.

PMID- 23158780
TI  - Widening social inequality in life expectancy in Denmark. A register-based study
      on social composition and mortality trends for the  Danish population.
AB  - BACKGROUND: Dynamics of the social composition of the population might influence
      the interpretation of statements of the increasing gap of social inequality in
      life expectancy. The aim of the study was to estimate trends during a quarter of
      a century in social inequality in life expectancy and to compare results based on
      different social stratifications. METHODS: Life tables by sex and various levels
      of education and income were constructed for each year in the period 1987-2011 by
      linking individual data from nationwide registers comprising information on all
      Danish citizens on date of birth, date of death, education and income. Trends in
      life expectancies were compared for different categories of social grouping of
      the population. RESULTS: When categories of educational level were kept fixed,
      implying a decreasing proportion of persons with a short education, the
      educational inequality in life expectancy increased. Thus, the difference in life
      expectancy at age 30 between men with primary or lower secondary education and
      men with tertiary education increased from 4.8 years in 1987 to 6.4 years in
      2011. For women the difference increased from 3.7 years in 1987 to 4.7 in 2011. A
      similar growing social disparity was observed when educational level was based on
      quartiles established from prescribed length of education. A considerable
      increasing inequality was reached for men when the population was divided in
      quartiles of equivalent disposable income, whereas the change was only modest for
      women. CONCLUSIONS: During the past 25 years, the social gap in life expectancy
      has widened in Denmark. This conclusion could not be explained by changes of the
      social compositions of the population.

PMID- 23158779
TI  - Prefrontal gray matter morphology mediates the association between serum
      anticholinergicity and cognitive functioning in early course schizophrenia.
AB  - Antipsychotic and other medications used in the treatment of schizophrenia place
      a burden on the cholinergic subsystems of the brain, which have been associated
      with increased cognitive impairment in the disorder. This study sought to examine
      the neurobiologic correlates of the association between serum anticholinergic
      activity (SAA) and cognitive impairments in early schizophrenia. Neurocognitive
      performance on measures of memory and executive function, structural magnetic
      resonance imaging (MRI) scans, and SAA assays were collected from 47 early
      course, stabilized outpatients with schizophrenia or schizoaffective disorder.
      Voxel-based morphometry analyses employing general linear models, adjusting for
      demographic and illness-related confounds, were used to investigate the
      associations between SAA, gray matter morphology, and neurocognitive impairment.
      SAA was related to working memory and executive function impairments. Higher SAA
      was significantly associated with lower gray matter density in broad regions of
      the frontal and medial-temporal lobes, including the dorsolateral prefrontal
      cortex (DLPFC), hippocampus, and striatum. Lower gray matter volume in the left
      DLPFC was found to significantly mediate the association between SAA and working
      memory impairment. Disease- and/or medication-related cholinergic dysfunction may
      be associated with brain volume abnormalities in early course schizophrenia,
      which may account for the association between SAA and cognitive dysfunction in
      the disorder.

PMID- 23158781
TI  - Fibular nonunion after closed-wedge high tibial osteotomy.
AB  - Closed-wedge valgus high tibial osteotomy (HTO) has been reported to be an
      effective procedure for the treatment of medial compartment osteoarthritis of the
      knee. It requires shortening the fibula, for which many techniques have been
      described. Dislocation of the proximal tibiofibular joint limits the correction
      angle of the procedure and the osteotomy of the fibular head runs the rare but
      dramatic risk of common fibular nerve palsy, which is why many surgeons perform
      the osteotomy more distally at the shaft. However, the potential complications of
      fibula shaft osteotomy in closed-wedge proximal tibial osteotomy have been poorly
      reported. The purpose of this study is to accurately define the incidence and
      risk of fibular complications. MATERIALS AND METHODS: One hundred and eight
      patients (59 men, 49 women, 53+/-10years old, preoperative varus: 6.7 degrees +/
      4 degrees ) underwent a closed-wedge HTO with fibular shaft osteotomy between
      1999 and 2004. They were followed up prospectively for clinical and radiological
      evaluation (2years of follow-up). The main evaluation criterion was the presence
      of fibular nonunion. RESULTS: Eighteen knees (16.6%) underwent fibular
      complications: 15 nonunions were indexed (13.9%); 11 of them (10.1%) required
      surgical revision. Three knees had nerve injury, with spontaneous recovery for
      two of them. DISCUSSION: Fibular nonunion is the most frequent complication,
      which often leads to revision procedures. Nonunion was correlated to the
      preoperative body mass index, the obliquity of the osteotomy plane, and the
      fragmentary contact. No nonunion was reported when the obliquity of the osteotomy
      plane was above 50 degrees  or the fragment contact greater than 50%. LEVEL OF
      EVIDENCE: Level IV, therapeutic study.

PMID- 23158782
TI  - Antibiotic prophylaxis to reduce the risk of joint implant contamination during
      dental surgery seems unnecessary.
AB  - INTRODUCTION: Joint implant infection rates range between 0.5% and 3%.
      Contamination may be hematogenous, originating in oro-dental infection and, as in
      endocarditis, antibiotic prophylaxis has been recommended to cover oro-dental
      surgery in immunodepressed patients with joint implants less than 2 years old,
      despite the lack of any formal proof of efficacy. In this context, the cost and
      side effects of such prophylaxis raise the question of its real utility.
      MATERIALS AND METHODS: A search of Pubmed was performed using the following
      keywords: prosthetic joint infection, dental procedure, antibiotic prophylaxis,
      hematogenous infection, dental infection, bacteremia, and endocarditis. Six
      hundred and fifty articles were retrieved, 68 of which were analyzed in terms of
      orthopedic prosthetic infection and/or endocarditis and oro-dental prophylaxis,
      as relevant to the following questions: frequency and intensity of bacteremia of
      oro-dental origin, frequency of prosthetic joint infection secondary to dental
      surgery, and objective efficacy of antibiotic prophylaxis in dental surgery in
      patients with joint implants. RESULTS: Bacteremia of oro-dental origin is more
      frequently associated with everyday activities such as mastication than with
      tooth extraction. Isolated cases of prosthetic contamination from dental
      infection have been reported, but epidemiological studies in joint implant
      bearers found that absence of antibiotic prophylaxis during oro-dental surgery
      did not increase the rate of prosthetic infection. The analysis was not able to
      answer the question of the efficacy of dental antibiotic prophylaxis in
      immunodepressed patients; however, oro-dental hygiene and regular dental
      treatment reduce the risk of prosthetic infection by 30%. DISCUSSION AND
      CONCLUSION: The present update is in agreement with the conclusions of ANSM
      expert group, which advised against antibiotic prophylaxis in oro-dental surgery
      in implant bearers, regardless of implant duration or comorbidity: the associated
      costs and risks are disproportional to efficacy. LEVEL OF EVIDENCE AND TYPE OF
      STUDY: Level V; expert opinion.

PMID- 23158783
TI  - Management of acute combination atlas-axis fractures with percutaneous triple
      anterior screw fixation in elderly patients.
AB  - INTRODUCTION: Patients with combined C1-2 fractures were often treated by
      posterior arthrodesis. However, elderly patients with multiple injuries (such as
      brain injury), the large surgical trauma of posterior arthrodesis will increase
      the risk of perioperative mortality. A minimally invasive technique may be better
      for them, and decrease the risk of perioperative mortality. MATERIALS AND
      METHODS: Seven patients with combined C1-2 fractures underwent percutaneous
      anterior odontoid screw and anterior C1-2 transarticular screws (percutaneous
      triple anterior screws fixation). The surgical technique of percutaneous triple
      anterior screws fixation is described. RESULTS: The operation performed on all
      patients successfully without technical difficulties, and no intra-operative
      surgery-related complications such as vertebral artery, nerve injury and soft
      tissue complications occurred. No pullout, loosening, or breakage of internal
      screws was observed. C1/2 stable was found in all cases and radiographic union
      achieved in all odontoid fractures. CONCLUSION: Using the appropriate instruments
      allied to intra-operative image-intensification, we suggest that percutaneous
      triple anterior screw fixation is reliable, effective and minimally invasive
      procedure for elderly and brain injured patients suffering of combined atlas-axis
      fractures. LEVEL OF EVIDENCE: Level IV. Retrospective study.

PMID- 23158784
TI  - Preoperative phlebography in anterior L4-L5 disc approach. Clinical experience
      about 63 cases.
AB  - INTRODUCTION: The anterior approach of the L4-L5 disc requires a perfect
      knowledge of the venous anatomy. Some configurations make this approach
      hazardous. The purpose of this study is to classify configurations of the
      iliocava junction and the iliolumbar vein relative to L4-L5 and to analyze
      vascular complications. MATERIALS AND METHODS: The preoperative phlebographies of
      63 patients (30 men, 33 women, mean age 42years) undergoing a L4-L5 disc
      replacement were reviewed. The height of the iliocava junction was calculated as
      a ratio of the distance between the discs L4-L5 and L5-S1. The position of the
      left iliac vein was classified into three thirds across the width of L5. The
      number of branches of the iliolumbar vein was noted. Surgical reports were
      reviewed for complications. RESULTS: The height of the iliocava junction was very
      high in six, high in 25, low in 26 and very low in six patients. The position of
      the left iliac vein was medial in 20, intermediate in 28 and lateral in 15
      patients. The iliolumbar vein had one branch in 37, two in 20, three in three
      patients. It was not visualized in three cases. Variants of the venous anatomy
      included eight duplications of the left iliac vein, four wide diameters and one
      iliolumbar vein network pattern. Intraoperatively, three lacerations of
      iliolumbar veins occurred. CONCLUSION: The iliocava anatomy is very variable: the
      safety of an anterior approach to the L4-L5 disc depends on it. The information
      of preoperative phlebography can help to plan a more accessible antero-lateral
      approach or to switch on a posterior fusion if the anatomical situation is deemed
      too dangerous, such as duplicated left iliac veins. LEVEL OF EVIDENCE: Level IV.
      Diagnostic study.

PMID- 23158785
TI  - Major amputation of lower extremity: prognostic value of positive bone biopsy
      cultures.
AB  - BACKGROUND: To assess the correlation between culture results of section's
      osseous slice biopsy (SOB) and the distal infected site responsible for the
      amputation performed concomitantly during major amputation of lower extremity.
      The influence of a positive culture of SOB on the patients' outcome was also
      evaluated. MATERIALS AND METHODS: We conducted a retrospective study of medical
      charts of patients who underwent SOB during major amputation of lower extremity
      at our institution from 2000 to 2009. RESULTS: Fifty-seven patients (42 males/15
      females, mean age 52.16years) who undergone major limb amputation (47 below knee
      and ten above knee) were included. The initial medical conditions of the
      investigated patients were: trauma (n=32), infection (n=13), trophic disorders
      (n=10) and tumor (n=2). The major cause of amputation was an uncontrolled
      infection, accouting for 64.9% of the cases (37/57) (foot=5, ankle=8, leg=24),
      the remaining 20 patients had trophic disorders of lower limb. Twenty-one (36.8%)
      from 57 biopsies were sterile, 12 (21.1%) doubtful and 24 (42.1%) positive.
      Thirty-one (54.4%) patients had an antibiotic-free interval before limb
      amputation. Independently of the bacterial species, 69.6% of the microorganisms
      identified from SOB were found in the distal infected site. Patients with
      positive SOB had a significantly longer interval between the decision to amputate
      the patient and the surgical procedure (200.2 vs. 70.1days; P<0.03) and a shorter
      total duration of antibiotic therapy before amputation than patients with
      negative SOB (3.68 vs. 6.08months; P<0.03). The delay for complete healing was
      significantly higher in patients with a positive SOB compared with those with a
      negative SOB (3.57 vs. 2.48months; P<0.03). CONCLUSION: Our results suggest that
      the infection may extend from the distal site to the level of amputation in a
      large proportion of cases and that the delay with which the amputation is
      performed after the decision has been taken may play a role in this event. LEVEL
      OF EVIDENCE: Study level IV: retrospective observationnal study.

PMID- 23158786
TI  - Surgical dural tears: prevalence and updated management protocol based on 1359
      lumbar vertebra interventions.
AB  - INTRODUCTION: The dural tear is a dreaded complication of lumbar surgery.
      HYPOTHESIS: Our management protocol has made it possible to deal with this
      problem effectively. MATERIALS AND METHODS: Retrospective review of 1359 patients
      operated between 2000 and 2010. In the event of dural tear, a therapeutic
      protocol was applied: suturing the dural wound if possible. A collagen patch
      lined with a layer of fibrin glue protected the suture. If the suture was
      considered tight, a non-aspirating drain was set up for 48h. In the other cases,
      no drain was set up. All the patients were left supine for 48h and they received
      intravenous antibiotics for the same duration. We analyzed the number and the
      type of breaches, the possibility of suturing, clinical symptoms (headache), and
      delayed complications (dural fistula or meningoceles). RESULTS: The 1359
      procedures included 23 dural tear complications (1.7%). The tears were often
      small in size and reparable. There were no late complications detected: no
      symptomatic fistula or meningocele. None of the patients had a second surgery.
      DISCUSSION: This protocol provided effective management of dural tears in lumbar
      surgery, with no application problems. We suggest a number of improvements: the
      use of the Valsalva maneuver to test the suturing, a stand-up test for the
      patient, and a systematic late MRI to detect meningoceles. There is no reason to
      change the other points in the protocol: suturing, controlled drainage for
      watertight wounds, no drainage for the non-watertight wounds, antibiotics, and
      supine bed rest position 48h. LEVEL OF EVIDENCE: Level IV. Retrospective study.

PMID- 23158787
TI  - Working alliance in communication skills training for oncology clinicians: a
      controlled trial.
AB  - OBJECTIVE: The aim of this study was to evaluate the impact of communication
      skills training (CST) on working alliance and to identify specific
      communicational elements related to working alliance. METHODS: Pre- and post
      training simulated patient interviews (6-month interval) of oncology physicians
      and nurses (N=56) who benefited from CST were compared to two simulated patient
      interviews with a 6-month interval of oncology physicians and nurses (N=57) who
      did not benefit from CST. The patient-clinician interaction was analyzed by means
      of the Roter Interaction Analysis System (RIAS). Alliance was measured by the
      Working Alliance Inventory - Short Revised Form. RESULTS: While working alliance
      did not improve with CST, generalized linear mixed effect models demonstrated
      that the quality of verbal communication was related to alliance. Positive talk
      and psychosocial counseling fostered alliance whereas negative talk, biomedical
      information and patient's questions diminished alliance. CONCLUSION: Patient
      clinician alliance is related to specific verbal communication behaviors.
      PRACTICE IMPLICATIONS: Working alliance is a key element of patient-physician
      communication which deserves further investigation as a new marker and efficacy
      criterion of CST outcome.

PMID- 23158788
TI  - [Four basic characteristics for clinical research].

PMID- 23158789
TI  - [Diagnosis of respiratory failure complicated by immunocompromised patients].

PMID- 23158790
TI  - [Metabolic syndrome and microalbuminuria accompanied with hyperglycemia in
      community subjects].
AB  - OBJECTIVE: To examine the prevalence of metabolic syndrome (MS) and
      microalbuminuria (MAU) in subjects with different levels of glucose tolerance and
      probe the risk factors for the development of MAU. METHODS: A total of 951
      subjects were divided into 3 groups according to the results of oral glucose
      tolerance test (OGTT). Among them, there were 674 subjects with normal glucose
      tolerance (NGT), 195 with impaired glucose regulation (IGR) and 82 newly
      diagnosed cases of type 2 diabetes mellitus (T2DM). MAU was diagnosed if urine
      albumin-to-creatinine ratio (UACR) was 30 - 300 mg/g. RESULTS: (1) Compared to
      the NGT subjects, both the IGR and newly-diagnosed T2DM subjects had the
      significantly higher levels of age, body mass index (BMI), waist circumference,
      fasting plasma glucose, 2-hour post OGTT glucose (2 hPG), glycated hemoglobin,
      glycated albumin, fasting insulin, homeostasis model of assessment-insulin
      resistance (HOMA-IR), triglyceride, systolic blood pressure (SBP) and UACR but a
      lower level of high density lipoprotein-cholesterol (HDL-C); (2) The incident
      rate of MS and MAU in the IGR and newly-diagnosed T2DM subjects was 54.4%
      (106/195), 12.3% (24/195) and 61.0% (50/82), 12.2% (10/82) respectively versus
      9.1% (61/674) and 4.9% (33/674) in the NGT subjects. The incident rate of
      abdominal obesity, hypertension, hypertriglyceridemia, low HDL-C, MS and MAU in
      the IGR and newly-diagnosed T2DM subjects was significantly higher than that of
      the NGT subjects (all P < 0.05); (3) Multiple regression analysis showed that
      BMI, SBP and 2 hPG were independently associated with UACR. Logistic regression
      analysis indicated that BMI, SBP and 2 hPG were independent risk factors of MAU.
      CONCLUSIONS: The prevalence of MS and MAU is significantly higher in the IGR and
      newly-diagnosed T2DM subjects. BMI, SBP and 2 hPG are independent risk factors of
      MAU.

PMID- 23158791
TI  - [Clinical significance of telomerase activity detection of myeloid element in
      immune related hematocytopenia].
AB  - OBJECTIVE: To observe the telomerase activity (TA) in bone marrow mononuclear
      cell (BMMNC) at pre-therapy and post-therapy in patients with immune related
      hematocytopenia and immune related pancytopenia (IRH/IRP) so as to explore the
      relationship between TA and disease process. METHODS: TA in BMMNC of 108 IRH/IRP
      patients was detected with telomeric repeat amplification protocol (TRAP)-PCR
      ELISA. The expressions of anti-human immunoglobulin IgG, FcgammaII receptor
      (FcgammaIIR), mannose receptor (MR) and interleukin 17A (IL-17A) located on
      membrane surface were observed by immunofluorescence (IF). A total of 30 iron
      deficiency anemia patients were selected as case control. RESULTS: The TA of 108
      IRH/IRP patients were 0.251 +/- 0.021. And it increased as compared with the
      control group of 0.062 +/- 0.031 at pre-therapy (P < 0.01). The HLA-B27(+)
      patients among them was 0.270 +/- 0.020 while HLA-B27(-) patients 0.181 +/- 0.013
      (P < 0.05). And HLA-B27(+)IgG elevated IRP was 0.341 +/- 0.016 and HLA-B27(-)IgG
      elevated 0.183 +/- 0.010, the difference of TA was significant between two groups
      (P < 0.01). IgG antibody positive immature hemocyte could be observed in marrow
      of IRH/IRP patients, and FcgammaIIR was expressed highly on those activated
      macrophage (Mphi) in bone marrow. Both IL-17A and MR were expressed on activated
      dendritic cells and Mphi in marrow of HLA-B27(+) patients. After the therapy of
      glucocorticoids associated with cyclosporine A and other drugs, the patient's
      hemogram recovered and the telomerase in BMMNC were re-devitalized. CONCLUSIONS:
      The TA of the BMMNC in marrow of IRH/IRP patients is increased, and it shows a
      close relation between apoptotic degree of hematopoietic cell and the activation
      of immunocytes. In IRH/IRP, synchronism and equilibrium exist between BMMNC
      apoptosis and TA.

PMID- 23158792
TI  - [Clinicopathologic features and prognostic analyses of Borrmann type IV gastric
      cancer].
AB  - OBJECTIVE: To compare Borrmann type IV gastric cancer with other types of cancer
      and explore their clinicopathological features and prognostic factors. METHODS:
      We retrospectively reviewed the medical records of 893 consecutive advanced
      gastric cancer patients. They were divided into 2 groups: Borrmann type IV (n =
      139) and other macroscopic Borrmann types of cancer (n = 754). Their
      clinicopathologic characteristics and overall survival data were analyzed.
      RESULTS: Borrmann type IV gastric cancer was found to be associated with more
      advanced and unfavorable clinicopathological features. The incidence of
      preoperative biopsy-negative rate of Borrmann type IV gastric cancer was much
      higher (15.9%) than other Borrmann types of gastric cancer. The 5-year survival
      rate of Borrmann type IV cancer patients was 9.9% and it was significantly lower
      than that of other types. Moreover, the 5-year survival rate was higher in the
      patients with curative resection (18.7%) (P < 0.05). Stratified analysis revealed
      that when the tumor TNM stages were of II, III, the survival data of Borrmann
      type IV cancer were worse than others. Multivariate analyses revealed distant
      metastasis and curability were independent prognostic factors for Borrmann type
      IV gastric cancer. CONCLUSIONS: Borrmann type IV carcinoma has poor
      clinicopathological features and survival rate compared with other types. An
      early detection and curative resection may improve the prognosis for the patients
      with Borrmann type IV cancer.

PMID- 23158793
TI  - [Feasibility of sentinel lymph node biopsy peri-neoadjuvant chemotherapy in
      breast cancer].
AB  - OBJECTIVE: To explore the feasibility of sentinel lymph node biopsy in peri
      neoadjuvant chemotherapy for breast cancer patients. METHODS: A total of 252
      breast cancer patients underwent sentinel lymph node biopsy and axillary lymph
      node dissection from January 2005 to November 2011, including 150 patients in pre
      neoadjuvant chemotherapy group and 102 in post-neoadjuvant chemotherapy group.
      The feasibility of sentinel lymph node biopsy under different clinical states of
      axillary lymph node was compared. RESULTS: No significant difference was found in
      the detection rate (98.5% vs 92.8%), false negative rate (6.7% vs 7.9%), accuracy
      (98.4% vs 91.9%) and negative sensitivity (97.9% vs 88.0%) of sentinel lymph node
      biopsy before neoadjuvant chemotherapy whether the axillary lymph node was
      negative or positive. However, the transfer rate of sentinel lymph node in the
      positive group was significantly higher than the negative group (28.8% vs 67.5%,
      P = 0.000). False negative rate of sentinel lymph node in biopsy was
      significantly higher in the post-neoadjuvant chemotherapy group than the pre
      neoadjuvant chemotherapy group (7.5% vs 23.9%, P = 0.024) and the
      accuracy/negative sensitivity decreased significantly (95.1% vs 83.5%, P =
      0.005/94.4% vs 75.0%, P = 0.003). No statistical difference existed in the
      detection rate, false negative rate, accuracy, negative sensitivity of sentinel
      lymph node in biopsy before and after neoadjuvant chemotherapy in patients with
      negative axillary lymph node for a preliminary diagnosis. The accuracy of
      sentinel lymph node decreased significantly in biopsy after neoadjuvant
      chemotherapy in patients with positive axillary lymph node confirmed
      pathologically for a preliminary diagnosis compared with before (98.4/83.7%, P =
      0.010), the transfer rate of sentinel lymph node increased significantly
      (28.8/53.7%, P = 0.005) and negative sensitivity reduced significantly
      (97.9/68.0%, P = 0.007); Compared with pre-neoadjuvant chemotherapy, the negative
      sensitivity decreased significantly in patients with axillary lymph node positive
      confirmed pathologically and then turned negative (94.4% vs 57.1%, P = 0.005)
      while the transfer rate of sentinel lymph node increased significantly
      (28.8%/65.0%, P = 0.003). CONCLUSIONS: Sentinel lymph node before neoadjuvant
      chemotherapy may accurately predict axillary lymph node metastasis. The detection
      rate, false negative rate, accuracy, negative sensitivity of sentinel lymph node
      in biopsy after neoadjuvant chemotherapy in patients with negative axillary lymph
      node for preliminary diagnosis are the same before neoadjuvant chemotherapy.
      Patients with positive axillary lymph node for a preliminary diagnosis are
      unsuitable for sentinel lymph node biopsy whether axillary lymph node turns
      negative or not after neoadjuvant chemotherapy.

PMID- 23158794
TI  - [A comparison of efficacies between transjugular intrahepatic portosystemic shunt
      versus portoazygos devascularization in the treatment of portal hypertension with
      variceal bleeding].
AB  - OBJECTIVE: To compare the efficacies between transjugular intrahepatic
      portosystemic shunt (TIPS) and portoazygos devascularization (PAD) in the
      treatment of portal hypertension with variceal bleeding. METHODS: From December
      1993 to December 2010, 309 patients with portal hypertension and variceal
      bleeding were admitted. According to their general conditions and Child-Pugh
      grades, they were assigned to undergo TIPS (group A, n = 235) or PAD (group B, n
      = 74). Before operation, compared with the PAD group, the TIPS group possessed
      worse liver functions, more severe ascites and a greater frequency of bleeding.
      After operation, the therapeutic efficacies and changes of portal hemodynamics,
      recurrent variceal bleeding, post-operative encephalopathy and long-term survival
      were evaluated between two groups. RESULTS: The postoperative portal pressure in
      the TIPS group ((42.6 +/- 7.0) vs (26.3 +/- 4.1) cm H2O) decreased much more than
      that in the PAD group ((38.7 +/- 5.2) vs (33.5 +/- 5.8) cm H2O, P < 0.01). The
      rebleeding rates during early postoperation were 0.85% (2/235) and 6.76% (5/74)
      in TIPS and PAD groups respectively, the occurring rates of hepatic
      encephalopathy 4.68% (11/235) and 4.05% (3/74) and the rates of operative
      mortality 1.70% (4/235) and 6.76% (5/74) respectively. Survival rates of 1, 3, 5
      and 10 years were 98.30% (231/235) vs 92.24% (69/74), 92.41% (146/158) vs 88.06%
      (59/67), 80.77% (84/104) vs 79.25% (42/53), 51.43% (36/79) vs 51.85% (14/27) in
      TIPS and PAD groups respectively. CONCLUSIONS: As compared with PAD, TIPS offers
      the such advantages as less trauma, wider indication, faster hemostasis and
      satisfactory therapeutic efficacies. Especially for the emergency treatment of a
      patient with massive variceal bleeding and Child-Pugh C grade liver function,
      TIPS is a better option than PAD.

PMID- 23158795
TI  - [Clinicopathological diagnosis of hypersensitivity pneumonitis].
AB  - OBJECTIVE: To enhance the understandings of clinical, radiological and
      pathological features of hypersensitivity pneumonitis (HP). METHODS: Six HP cases
      with pathological data, clinical and radiological data were retrospectively
      analyzed during the period from February 2009 to September 2011 at Beijing
      Hospital of Ministry of Health. There were 2 males and 4 females with a mean age
      of 51.5 years (range: 38-61). Clinically, the patients presented with chronic
      cough, shortness of breath and dyspnea (n = 2). The disease course was 1-8
      months. Five cases had fed pigeons and other contact histories. Specimens
      obtained by transbronchial lung biopsy (n = 3) and open lung biopsy (n = 3) were
      paraffin embedded and stained by hematoxylin and eosin, special stains and
      immunohistochemistry. RESULTS: Four cases had subacute HP and 2 cases chronic HP.
      Three cases of subacute HP underwent transbronchial lung biopsy. One case of
      subacute HP and 2 cases of chronic HP were diagnosed by open lung biopsy. High
      resolution computed tomography of lungs showed diffuse ground glass and patch
      shadow along the bronchial and centrilobular distributions. There was a
      predominance of upper half zone. Typical visible mosaic syndrome was present.
      There was poorly formed granuloma without cheesy necrosis. With an insidious
      medical history and complicated radiological features, chronic HP cases were
      characterized by pulmonary interstitial fibrosis. There were usual interstitial
      pneumonitis (UIP)-like fibrosis and fibrosis with an airway-centered distribution
      type. The lesions were distributed around bronchioles. Continuous bridge fibrosis
      might be present. There were bronchiolar metaplasia of peribronchiolar alveoli,
      poorly formed granuloma and multinucleated giant cells in interstitium. Schaumann
      body was identified in 1 case. CONCLUSIONS: Because of its diverse clinical,
      radiological and pathological features, HP may be easily confused with other
      interstitial lung diseases. Aggregate analyses yield a definite diagnosis.

PMID- 23158796
TI  - [Analysis of medication with hypertension by different glucose tolerance status].
AB  - OBJECTIVE: To analyze the combination of hypertension and the use of
      antihypertensive drugs by different glucose tolerance status. METHODS: Matched
      case-control design was used to sample the subjects from the population for the
      prevalence of diabetes mellitus and metabolism syndrome from 2007 to 2008. There
      were 3 groups including normal glucose tolerance (NGT, n = 2124), impaired
      glucose regulation (IGR, n = 2162) and diabetes (DM, n = 2470). The matched
      factors were location, age and gender. All subjects were interviewed to describe
      the hypertension and antihypertensive drugs of these conditions. RESULTS: After
      adjusting for age, gender and location, the combination of hypertension in IGR
      and DM groups was higher than NGT (28.3%, 40.2% and 19.9%) and OR was 1.29 (1.08 
      1.53) and 1.99 (1.67 - 2.37) respectively. The percent of treatment,
      prescription compliance and the surveillance of hypertension in total subjects
      were 48.6%, 79.3% and 62.5%. And no difference was observed among 3 groups. The
      proportion of calcium channel blocker of DM groups was higher than NGT group. The
      uses of angiotensin-converting enzyme inhibitors (ACEI) and angiotensin II
      receptor blocker (ARB) showed no difference among 3 groups. CONCLUSIONS: The
      combination of hypertension is higher in IGR and DM groups than that in NGT
      group. And the treatment rate of hypertension remains low. ACEI and ARB are under
      utilized in IGR and DM groups.

PMID- 23158797
TI  - [Causes of anastomotic leakage after colorectal cancer laparoscopic-assisted
      surgery].
AB  - OBJECTIVE: To explore the causes of postoperative anastomotic leakage of
      colorectal cancer. METHODS: A total of 1462 cases with colorectal cancer
      undergoing laparoscopic operation and intestinal anastomosis at our department
      over the last decade were analyzed retrospectively. Data analysis was performed
      with SPSS 13.0. The risk factors were analyzed by binary Logistic regression
      while the annual incidence of anastomotic leakage by trend chi(2) test. RESULTS:
      Thirty anastomotic leakage occurred in 1462 cases with an incidence rate of 2.1%.
      There were significant correlations of anastomotic leakage with body built, tumor
      location, tumor size, operation time (chi(2) = 6.117, 50.167, 36.693, 4.481, P =
      0.013, 0.000, 0.000, 0.034). However, there was no correction with gender, age or
      histological type (P = 0.871, 0.775, 1.000). Then the significance check of
      binary Logistic regression equation was performed. Tumor location was an
      independent risk factor of postoperative anastomotic leakage for colorectal
      cancer. The relative risk was 2.056. The annual incidence of anastomotic leakage
      was statistically insignificant (chi(2) = 1.827, P = 0.176). And the difference
      was. CONCLUSIONS: The occurrence of anastomotic leakage after colorectal cancer
      surgery is significantly correlated with body built, tumor location, tumor size
      and operation time. And tumor location below peritoneal reversal is an
      independent risk factor of anastomotic leakage.

PMID- 23158798
TI  - [Effect of Akt on the function of esophageal squamous cancer cell Eca109 and the
      expression of vasculogenic mimicry-related genes].
AB  - OBJECTIVE: To investigate the inhibitory effect of siRNA targeting Akt on the
      biological behavior of esophagus squamous cell carcinoma cell line in vitro and
      to explore the relationship between Akt and vasculogenic mimicry (VM)-related
      genes in esophageal squamous cell carcinoma. METHODS: The plasmid-harboring small
      interfering RNA targeting Akt was introduced into Eca109 cells by liposome
      mediated transfection. The proliferation of Eca109 cell was determined by colony
      formation assay. The cellular migration was evaluated by Transwell migration
      assay. And three dimensional cell culture was employed to observe and count the
      number of capillary structure for each cell group. Flow cytometry (FCM) was used
      to detect the apoptotic rate of Eca109, Eca109/Neo and Eca109/siRNA Akt cells
      under normoxia exposure. The apoptotic rate was assessed by Annexin V/7-AAD
      double labeling. And the expressions of Akt and matrix metalloproteinase-2 (MMP
      2) protein were detected by Western blotting. RESULTS: The results of Western
      blotting showed that the expression of Akt in stably transfected group were
      significantly lower than empty carrier and untransfected groups (0.03 +/- 0.01 vs
      1.49 +/- 0.39 and 1.47 +/- 0.41, both P < 0.05). Transwell migration assay showed
      that fewer Eca109/8 cells could move through the artificial basement membrane as
      compared with untransfected and empty carrier groups (48 +/- 9 vs 128 +/- 10 and
      122 +/- 11, both P < 0.05). Clone formation number of stably transfected group
      was significantly lower than empty carrier and untransfected groups (63 +/- 7 vs
      148 +/- 11 and 163 +/- 15, both P < 0.05). Annexin V/7-AAD double standard method
      demonstrated that the apoptotic rate of stably transfected group was much more
      than those of untransfected and empty carrier groups (12.2% +/- 1.6% vs 4.8% +/-
      0.8% and 4.2% +/- 0.8%, both P < 0.05). Eca109 and Eca109/Neo cells were capable
      of forming the in vitro structures of VM. And the number of tube-shaped structure
      in stably transfected group was markedly less than those of untransfected and
      empty carrier groups (14.0 +/- 1.2 vs 30.0 +/- 1.2 and 27.7 +/- 1.5, both P <
      0.05). MMP-2 protein expression in stably transfected group was less than those
      of untransfected and empty carrier groups (both P < 0.05). CONCLUSIONS: The
      PI(3)K/Akt pathway is involved in the regulation of VM formation in esophageal
      squamous cell carcinoma through the action of MMP-2. Blockade of this pathway may
      provide a new therapeutic approach to human esophagus squamous cell carcinoma.

PMID- 23158799
TI  - [Effects of icotinib hydrochloride on the proliferation and apoptosis of human
      lung cancer cell lines].
AB  - OBJECTIVE: To explore the effects of icotinib on the proliferation and apoptosis
      of various lung cancer cell lines. METHODS: Human lung cancer cell lines HCC827,
      H1650, H1975, A549 and human epidermal cancer cell line A431 were treated in
      vitro with icotinib or gefitinib at a concentration gradient of 0 - 40 umol/L.
      Their proliferation effects were analyzed by the thiazolyl blue (MTT) assay and
      the apoptotic effects detected by flow cytometer. The downstream signaling
      proteins were detected by Western blot. RESULTS: The median inhibitory
      concentrations (IC(50)) of icotinib for A431 and HCC827 cell lines were (0.04 +/-
      0.02) and (0.15 +/- 0.06) umol/L respectively. No significant differences existed
      between the inhibitions of gefitinib and icotinib on A431, HCC827, H1650, H1975
      and A549 cell lines (all P > 0.05). Compared with H1650, H1975 and A549 cell
      lines, icotinib significantly inhibited A431 (P = 0.009, 0.005 and 0.000) and
      HCC827 (P = 0.001, 0.001 and 0.000) cell lines. And it lowered the expressions of
      p-AKT, p-ERK and survivin protein expression through the inhibited activity of p
      EGFR protein. CONCLUSION: Icotinib can arrest the proliferation of lung
      adenocarcinoma cells with EGFR mutation or over-expression by inhibiting the
      signal pathways of AKT-ERK and survivin.

PMID- 23158800
TI  - [Expression and significance of neutrophil gelatinase-associated lipocalin in
      renal interstitial fibrosis in rats].
AB  - OBJECTIVE: To explore the expression and significance of neutrophil gelatinase
      associated lipocalin(NGAL)in renal interstitial fibrosis (RIF) in rats. METHODS:
      A total of 60 male Sprague-Dawley rats were randomly divided into 3 groups of
      sham operation (SOR), unilateral ureteral obstruction (UUO) and angiotensin
      converting enzyme inhibitor (ACEI). The serum concentrations of NGAL and tumor
      necrosis factor-alpha (TNF-alpha) were detected by enzyme-linked immunosorbent
      assay (ELISA). And the expressions of NGAL, matrix metalloproteinase-9 (MMP-9)
      and transforming growth factor-beta1 (TGF-beta1) were observed by
      immunohistochemistry. RESULTS: (1) The levels of serum NGAL and TNF-alpha in UUO
      group obviously increased as compared to those in ACEI and SOR groups (NGAL:
      (69.2 +/- 5.6) vs (41.0 +/- 10.4), (10.8 +/- 3.8) pg/ml; TNF-alpha: (116.2 +/-
      9.2) vs (99.8 +/- 14.0), (29.2 +/- 5.7) ng/ml; all P < 0.05). (2) The expressions
      of NGAL, TGF-beta1 and MMP-9 in renal tubular epithelial cells of UUO group
      increased as compared to those in SOR group. The expression of TGF-beta1 in ACEI
      group was apparently less than that in UUO group. The protein levels of NGAL and
      MMP-9 in ACEI group were obviously lower than those in UUO group within Day 14
      post-operation and significantly higher than those in UUO group at Days 21 and
      28. (3) In UUO group, the level of NGAL was positively correlated with the serum
      levels of TNF-alpha and serum creatinine (r = 0.910, 0.673, P < 0.01). The
      expression of NGAL had a highly positive correlation with MMP-9 (r = 0.913, P <
      0.01) and the index of interstitial damage and the degrees of TGF-beta1 at Days 3
      7 post-operation(r = 0.937, 0.847, P < 0.01). And the expression of NGAL was
      negatively correlated with the index of interstitial damage and the degrees of
      TGF-beta1 at Days 14-28 post-operation (r = -0.945, -0.944, P < 0.01).
      CONCLUSION: The expression of NGAL significantly increases in UUO modal of rats.
      And it is closely correlated with MMP-9, TNF-alpha and TGF-beta1. ACEI may
      influence the biological effects of NGAL by suppressing inflammatory responses,
      down-regulating the expression of TGF-beta1 and regulating the expression and the
      activity of MMP-9.

PMID- 23158801
TI  - [Mechanism of p38 mitogen-activated protein kinase inhibitor SB203580 to
      glucocorticoid sensitivity].
AB  - OBJECTIVE: To establish a model of cigarette smoke exposure to asthmatic rats and
      glucocorticoid resistance induced by nicotine in alveolar epithelioid cells A549
      and study the mechanism for the change of glucocorticoid sensitivity induced by
      p38 mitogen-activated protein kinase (p38 MAPK) inhibitor SB203580. METHODS:
      Sixty Wistar rats were randomly divided into 4 groups: normal group, asthmatic
      group, cigarette smoke exposure to asthmatic group and SB203580 group. The mRNA
      expressions of glucocorticoid receptor (GR), heat shock protein 90 (HSP90) and
      p38 MAPK were detected by real time-polymerase chain reaction (RT-PCR) while
      their protein expressions detected by Western blot in vivo. A549 cells were
      divided averagely into 4 groups: group A: normal; group B: 1 umol/L dexamethasone
      (DEX); group C: 1 umol/L DEX +1 umol/L nicotine; group D: 1 umol/L DEX +1 umol/L
      nicotine+1 umol/L SB203580. Immunofluorescence staining was used to study the in
      vitro colocalization of glucocorticoid receptor (GR) in A549 cells. RESULTS: The
      mRNA expression of GR was 0.671 +/- 0.002 in cigarette smoke exposure to
      asthmatic group and 0.595 +/- 0.061 in SB203580 group (P = 0.065). The protein
      expression of GR was 0.700 +/- 0.033 in cigarette smoke exposure to asthmatic
      group and 0.628 +/- 0.091 in SB203580 group (P = 0.148). The mRNA expression of
      HSP90 was 0.558 +/- 0.009 in cigarette smoke exposure to asthmatic group and
      0.377 +/- 0.046 in SB203580 group (P = 0.000). The protein expression of HSP90
      was 0.507 +/- 0.030 in cigarette smoke exposure to asthmatic group and 0.402 +/-
      0.050 in SB203580 group (P = 0.005). The mRNA expression of p38 MAPK was 0.971 +/
      0.012 in cigarette smoke exposure to asthmatic group and 0.278 +/- 0.049 in
      SB203580 group (P = 0.000). The protein expression of p38 MAPK was 0.982 +/-
      0.038 in cigarette smoke exposure to asthmatic group and 0.338 +/- 0.042 in
      SB203580 group (P = 0.000). The ratio of GR amount within A549 nucleus versus
      that in cytoplasm was 0.077 +/- 0.047 in group C and 0.592 +/- 0.249 in group D
      (P = 0.000). CONCLUSION: The mechanism of SB203580 enhancing the corticosteroid
      sensitivity may be improving nuclear translocation of GR to elevate
      corticosteroid sensitivity.

PMID- 23158802
TI  - [Method of expansion of late endothelial progenitor cells].
AB  - OBJECTIVE: To validate a novel method of expanding late endothelial progenitor
      cells (EPC) in vitro. METHODS: We cultured mononuclear cells (MNC) from human
      peripheral blood on the plate with the feeder layer cells, i.e. irradiated late
      EPC or human umbilical vein endothelial cells. After 21 days, the numbers of late
      EPC colonies were counted separately. And the surface antigen of late EPC was
      detected by fluorescence-activated cell sorter (FACS) and their in vitro ability
      of forming vascular structure examined by matrigel. RESULTS: Both colony numbers
      of late EPC with feeder layer cell culturing were over 20 times than those
      without (40.0 +/- 3.9, 39.3 +/- 3.1 vs 2.0 +/- 1.3, both P < 0.05). And the
      former's late EPC colony appeared earlier. The late EPC expressed CD31, CD34,
      eNOS, Flt-1, P1H12, Sendo, VE cadherin and CD117. And vascular structures were
      discerned. CONCLUSIONS: The method of feeder layer cells may vastly expand the
      quantity of late EPC. And microenvironment plays an important role in its
      expansion.

PMID- 23158803
TI  - Non-high density lipoprotein cholesterol versus low density lipoprotein
      cholesterol as a discriminating factor for myocardial infarction.
AB  - BACKGROUND: Serum total cholesterol (TC) and LDL cholesterol (LDL-C) have been
      used as major laboratory measures in clinical practice to assess cardiovascular
      risk in the general population and disease management as well as prognosis in
      patients. However, some studies have also reported the use of non-HDL cholesterol
      (non-HDL-C). As non-HDL-C can be calculated by subtracting HDL-C from TC, both of
      which do not require fasting blood sample in contrast to LDL-C which requires
      fasting blood sample, we aimed to compare non-HDL-C with LDL-C as a predictor of
      myocardial infarction (MI). METHODS: This hospital based cross sectional study
      was undertaken among 51 cases of MI and equal number of controls. MI was
      diagnosed based on the clinical history, ECG changes and biochemical parameters.
      5 mL of fasting blood sample was collected from each research participant for the
      analysis of lipid profile. Non-HDL-C was calculated by using the equation; Non
      HDL-C = TC - HDL-C. Statistical analysis was performed using SPSS 14.0. RESULTS:
      42 MI cases were dyslipidemic in contrast to 20 dyslipidemic subjects under
      control group. The differences in the median values of each lipid parameter were
      statistically significant between MI cases and controls. The lipid risk factors
      most strongly associated with MI were HDL-C (OR 5.85, 95% CI 2.41-14.23, P value
      = 0.000) followed by non-HDL-C (OR 3.77, 95% CI 1.64-8.66, P value = 0.002), LDL
      C/HDL-C (OR 3.38, 95% CI 1.44-7.89, P value = 0.005), TC/HDL-C (OR 2.93, 95% CI
      1.36-7.56, P value = 0.026), LDL-C (OR 2.70, 95% CI 1.20-6.10, P value = 0.017),
      TC (OR 2.68, 95% CI 1.04-6.97, P value = 0.042) and Tg (OR 2.54, 95% CI 1.01
      6.39, P value = 0.047). Area under the receiver operating curve was greater for
      non-HDL-C than for LDL-C. Non-HDL-C was also found to be more sensitive and
      specific than LDL-C for MI. CONCLUSIONS: HDL-C and non-HDL-C are better
      discriminating parameters than LDL-C for MI. Thus, we can simply perform test for
      HDL-C and non-HDL-C both of which do not require fasting blood sample rather than
      waiting for fasting blood sample to measure LDL-C.

PMID- 23158804
TI  - Effectiveness of early medical abortion using low-dose mifepristone and buccal
      misoprostol in women with no defined intrauterine gestational sac.
AB  - BACKGROUND: The study was conducted to assess the effectiveness of early medical
      abortion (EMA) in women with early pregnancy and no defined intrauterine
      gestational sac (IUGS) on ultrasound. STUDY DESIGN: Retrospective, multicenter,
      observational study of oral mifepristone 200 mg and buccal misoprostol 800 mcg
      administered 24-48 h later for EMA (gestations <= 63 days). Odds ratios (ORs)
      [95% confidence intervals (CIs)] of EMA failure and continuing pregnancy for
      women with no defined IUGS vs. those with confirmed IUGS were calculated.
      RESULTS: Women with no defined IUGS were more likely to experience EMA failure
      [9.0% (6/67) vs. 3.5% (465/13,345); OR (95% CI)=2.72 (1.17-6.33), p=.041] and
      continuing pregnancy [7.5% (5/67) vs. 0.6% (83/13,345); OR (95% CI)=12.72 (4.98
      32.46), p<.001]. CONCLUSION: EMA failure is more likely in women with early
      pregnancy and no defined IUGS than those with gestations <= 63 days and confirmed
      IUGS.

PMID- 23158805
TI  - Characteristics associated with interest in long-acting reversible contraception
      in a postpartum population.
AB  - BACKGROUND: Short interpregnancy intervals lead to adverse perinatal outcomes and
      could be prevented with increased use of long-acting reversible contraception
      (LARC) in the postpartum period. The primary objective of this study was to
      assess which baseline characteristics are associated with the intent to use LARC
      among postpartum women. STUDY DESIGN: This study was a substudy of baseline data
      from a randomized controlled trial. Eight hundred women completed a pre
      intervention survey of demographics and reproductive health history and
      intentions. We estimated adjusted relative risks (RRs) of intent to use LARC for
      baseline characteristics of interest. RESULTS: Three hundred three postpartum
      women (38%) intended to use LARC. Two out of 10 baseline characteristics were
      significantly associated with intent to use LARC: not trying for pregnancy at
      time of conception [adjusted RR, 1.6; 95% confidence interval (CI), 1.2-2.1] and
      no desire for another pregnancy within 2 years (adjusted RR, 1.9; 95% CI, 1.2
      2.8). CONCLUSIONS: High interest in LARC exists among postpartum women,
      particularly among women with a recent unintended pregnancy and women who do not
      desire pregnancy for at least 2 years. Past and future pregnancy intentions
      should be incorporated into future models and frameworks that evaluate postpartum
      contraceptive choice. Educational intervention studies are also needed to assess
      if LARC interest can be increased among postpartum women who are less likely to
      intend to use LARC but at risk for future adverse perinatal outcomes.

PMID- 23158806
TI  - Pharmacokinetics and adhesion of the Agile transdermal contraceptive patch (AG200
      15) during daily exposure to external conditions of heat, humidity and exercise.
AB  - BACKGROUND: This study compares the pharmacokinetic profile, adhesion and safety
      of the AG200-15 Agile Patch (AP), a novel contraceptive patch releasing low-dose
      ethinyl estradiol (EE) and levonorgestrel (LNG), during wear under external
      conditions of heat, humidity and exercise versus normal activities. STUDY DESIGN:
      This open-label, three-period, five-treatment, crossover study randomized 24
      healthy women to one of six external condition sequences. Each sequence included
      one normal wear and two external conditions periods. Participants wore the AP for
      7 days under normal conditions or conditions of daily sauna, treadmill, whirlpool
      or cool water immersion, with a 7-day washout between treatments. Blood samples
      were collected for pharmacokinetic evaluations. RESULTS: Twenty-four subjects
      completed the study. For EE, the mean maximum concentration level (Cmax), area
      under the plasma concentration-time curve from time 0 to 168 h (AUC(0-168)) and
      area under the plasma concentration-time curve from time 0 to infinity (AUC(0
      inf)) were higher during normal conditions compared with all external conditions
      (geometric means ratio range: 80%-93%), except cool water. Mean steady-state
      concentrations (C(ss)) of EE were highest under normal conditions, followed by
      cool water, sauna, whirlpool and treadmill. The LNG mean C(max), AUC(0-168),
      AUC(0-inf) and C(ss) were higher under normal wear versus all other conditions
      (geometric means ratios: 75%-82%), with the exception of AUC(0-168), AUC(0-inf)
      and C(ss) for cold water. Median times to maximum concentration (Tmax) for EE and
      LNG were comparable across conditions. Patch adhesion was excellent under all
      conditions. Adverse events were mild, with none serious or leading to
      discontinuation. CONCLUSIONS: Although slightly lower mean drug concentration
      levels were observed for whirlpool, treadmill and sauna, drug concentrations
      under all conditions were well within therapeutic ranges established for the AP
      during normal wear and within ranges reported for low-dose combination oral
      contraceptives. Patch adhesion was excellent; the AP was safe and well tolerated
      under all conditions.

PMID- 23158807
TI  - Effect of antiviral therapy on the survival and incidence of major complications
      in HBV-associated cirrhotic patients after splenectomy for hypersplenism and
      portal hypertension.
AB  - BACKGROUND: Splenectomy remains a common approach for the management of
      hypersplenism and portal hypertension in hepatitis B virus (HBV)-associated
      cirrhotic patients in China and some other Asian countries. The effects of
      antiviral therapy on the survival and occurrence of complications in asplenic HBV
      associated cirrhotic patients are unknown. This study analyzed the effect of
      antiviral therapy on survival and occurrence of major complications in HBV
      associated cirrhotic patients after splenectomy for hypersplenism and portal
      hypertension. RESULTS: Of the 57 eligible patients for analysis, 28 patients
      received nucleos(t)ide analogs (treatment group) for antiviral treatment after
      splenectomy, while 29 patients received no antiviral treatment (control group).
      After a median of 3 years and 9 months, the overall survival and complication
      free survival in the treatment group were higher though not statistically
      significant than those in the control group. Multivariate analysis showed that
      antiviral treatment was associated with increased but not statistically
      significant overall survival (hazard ratio (HR): 2.272, 95% confidence interval
      (CI): 0.952-5.424, P=0.064) and the antiviral treatment was significantly
      associated with increased complication-free survival of the patients (HR: 7.229,
      95% CI: 1.271-41.117, P=0.026). The complication-free survival in patients aged
      <= 40 years was higher than that in patients aged>40 years in the antiviral
      treatment patients (P=0.020). CONCLUSIONS: Antiviral therapy initiating after
      splenectomy may reduce the incidence of complications and tend to improve the
      survival in asplenic HBV-associated cirrhotic patients, especially in younger
      patients, supporting the use of antiviral therapy in these patients after
      splenectomy.

PMID- 23158809
TI  - Monitoring the cognitive effects of antiepileptic pharmacotherapy--approaching
      the individual patient.
AB  - Cognitive side effects of antiepileptic drugs are common and can negatively
      affect tolerability, compliance, and long-term retention of the treatment.
      Furthermore, adverse cognitive effects of pharmacotherapy significantly affect
      everyday functioning and quality of life. Consequently, preservation of cognitive
      functions is an important aspect of epilepsy therapy. Knowledge of the patient's
      neuropsychological status before and after pharmacological interventions can help
      to decide on the appropriate treatment and, thus, can potentially improve
      individual medical care. Here, we suggest that cognitive monitoring of
      antiepileptic pharmacotherapy--like the assessment of seizure frequency, blood
      serum levels, electroencephalography or structural imaging--should be carried out
      as a matter of routine. In contrast to subjective measures, there are only very
      few neuropsychological instruments explicitly validated for the assessment of
      cognition along with antiepileptic pharmacotherapy. This review (1.) outlines
      indications and requirements for individual cognitive monitoring, (2.) discusses
      available diagnostic tools, and (3.) discloses relevant pitfalls.
      Neuropsychology, as demonstrated, provides evidence-based methods for monitoring
      cognitive effects of individual pharmacological treatments and, therefore, serves
      as a valuable tool for the quality and outcome control of antiepileptic
      therapies.

PMID- 23158808
TI  - Testimonies submitted for the Institute of Medicine report: epilepsy across the
      spectrum: promoting health and understanding.
AB  - The 2012 Institute of Medicine (IOM) report, Epilepsy Across the Spectrum:
      Promoting Health and Understanding, provides a vision for moving the field
      forward to improve the lives of people with epilepsy. The committee made 13
      recommendations and identified a number of research priorities to promote
      accomplishing this vision. Its work was enriched by the contributions of many
      individuals who testified before the committee during its two public workshops
      and who submitted written testimony throughout the study process. Many of these
      testimonies included in this article were presented in-person at the committee's
      public workshops in Los Angeles, CA on March 21, 2011 and in Washington, DC on
      June 28-29, 2011. Among those providing testimony were people with epilepsy,
      their family members, health care professionals, and researchers specializing in
      epilepsy. The 36 testimonies that comprise this publication provided the
      committee with a more complete and current picture of epilepsy-related health
      care issues and the challenges that epilepsy imposes on the lives of people with
      epilepsy and their families.

PMID- 23158810
TI  - [Chinese Journal of Pediatrics: a good teacher and a helpful friend of
      pediatricians].

PMID- 23158811
TI  - [Pay attention to sedation and analgesic therapy in critically ill children].

PMID- 23158812
TI  - [Emergency use of extracorporeal membrane oxygenation in pediatric critically ill
      patients].
AB  - OBJECTIVE: The history of clinical application of extracorporeal membrane
      oxygenation (ECMO) has been more than 30 years. But in China, there were only a
      few ECMO centers with limited successful cases reported by the end of twentieth
      century. The high morbidities and mortalities in current pediatric ECMO practice
      are noted in China. Therefore, it is necessary to review the experience on rescue
      use of ECMO in critically ill pediatric patients. METHOD: A retrospective
      analysis was done for patients who had been receiving ECMO treatment to rescue
      refractory cardiorespiratory failure from different causes in a hospital between
      July 2007 and May 2011. RESULT: A total of 12 patients were treated with ECMO; 7
      of them were male and 5 female, they aged 6 days to 11 years, weighed 2.8 - 35
      (17.21 +/- 11.64) kg. The underlying causes of cardiorespiratory failure were as
      follows: two cases with acute respiratory distress syndrome (ARDS) leading to
      respiratory failure, 4 with failure of weaning from cardiopulmonary bypass, 3
      with fulminant myocarditis, 1 with right ventricular cardiomyopathy leading to
      repeated cardiac arrest, 1 with preoperative severe hypoxemia, and 1 with
      anaphylactic shock complicated with massive pulmonary hemorrhage and severe
      hypoxemia. Of the 12 cases, 3 were established ECMO (E-CPR) while underwent chest
      compression cardiopulmonary resuscitation (CPR). The mean ECMO support time was
      151.75 (15 - 572) h. Seven patients (58.33%) were weaned from ECMO, 6 patients
      (50.00%) were successfully discharged. Six cases had bleeding from sutures, 2
      cases with severe bleeding underwent thoracotomy hemostasis, 2 presented with
      acute renal failure. Infection was documented in 3 cases, hyperbilirubinemia in 2
      cases, lower limb ischemia in 1 case, hyperglycemia in 3 cases, disseminated
      intravascular coagulation in 1 case, membrane lung leakage in 2 cases, systemic
      hemolysis in 3 cases, oxygenator failure in 2 cases and oxygenator thrombosis in
      one case. During the follow-up between 6 months and 4.5 years, 5 patients
      survived with good quality of life, without any documented central nervous system
      disorders. One case survived with the right lower extremity disorder from
      ischemic damage. His motor function has been improved following orthopedic
      operation at one year after discharge. CONCLUSION: ECMO is a justifiable
      alternative treatment for reversible severe cardiopulmonary failure in critically
      ill children.

PMID- 23158813
TI  - [Changes and significance of soluble CD 163 in sepsis and severe sepsis in
      children].
AB  - OBJECTIVE: To investigate the changes of serum soluble CD 163 (sCD 163) level, to
      assess the severity of critical illness and to evaluate the immune status of
      sepsis or severe sepsis in children. METHOD: A prospective study was conducted.
      The sCD 163 was determined in 50 cases with sepsis or severe sepsis in pediatric
      intensive care unit (PICU) and 23 cases of age- and gender-matched healthy
      children were enrolled as control during the period from April 2010 to March
      2011. Double-antibody sandwich ELISA was used for sCD 163 measurement. The
      relationship with sCD 163 level and disease severity score (pediatric critical
      illness score, PCIS; and pediatric risk of mortality III, PRISM III), lymphocyte
      subsets, C-reactive protein (CRP), tumor necrosis factor alpha (TNFalpha) were
      analyzed. RESULT: The sCD 163 in sepsis/severe sepsis groups (171.04 +/- 177.85)
      mg/L was significantly higher than that in control group (44.19 +/- 86.48) mg/L
      (P < 0.01).sCD 163 in sepsis group [(105.32 +/- 145.87) mg/L] was significantly
      lower than that of severe sepsis group [(233.32 +/- 171.78) mg/L] (P < 0.05). sCD
      163 level was significantly higher in lower PCIS score patients. (P < 0.01). The
      sCD 163 levels was higher in PRISM III >= 10 than the PRISM III < 10 group. The
      sCD 163 levels were higher in death group than the survival group. The sCD 163
      was negatively correlated with CD4 +, CD4 +/CD8 + (R = -0.820, P < 0.05; R = 
      0.839, P < 0.01). CONCLUSION: Detection of sCD 163 was helpful in predicting the
      severity of sepsis and severe sepsis, and sCD 163 may reflect the immune status
      of critically ill children with sepsis.

PMID- 23158814
TI  - [Changes of drug-resistance of Pseudomonas aeruginosa in pediatric intensive care
      unit].
AB  - OBJECTIVE: Pseudomonas aeruginosa is an important cause of nosocomial infection,
      severe sepsis and death which associated with a trends of rising rates of
      resistance to a broad array of antimicrobial agents. To explore a feasible
      treatment protocol for such patients, we analyzed the susceptibility patterns of
      Pseudomonas aeruginosa in pediatric intensive care unit (PICU). METHOD: The age
      distribution, outcome of patients, sources of strains and susceptibility patterns
      of Pseudomonas aeruginosa in PICU from Jan 1, 2007 to Dec 31, 2011 were analyzed.
      Susceptibility to amikacin, piperacillin/tazobactam, aztreonam, ampicillin,
      ciprofloxacin, imipenem, meropenem, cefepime, cefoperazone, cefotaxime,
      ceftriaxone, ceftazidime, cefoperazone/sulbactam, cephazolin, cefuroxime, and
      polymyxin were determined by the disk-diffusion technique (K-B test method) and
      broth microdilution. P. aeruginosa ATCC 27853 was used as reference strain.
      RESULT: Seventy-five patients were Pseudomonas aeruginosa positive. 26(34.7%)
      were < 6 m, 49 (65.4%) were < 2 y. The percentages of cases who were Pseudomonas
      aeruginosa positive in different age groups in the same time was basically
      similar; 18 (24.0%) cases died. Pseudomonas aeruginosa accounted for 10.9% of G(
      ) germs, 6.5% of all pathogens in 2010 - 2011. Of the 126 strains, 83 (65.9%)
      were from sputum sample, 31 (24.6%) were from catheter sample of tracheal
      cannula, 10 (7.9%) were from blood sample and 2 (1.6%) were from secretion
      sample. The sensitivity to antibiotics of Pseudomonas aeruginosa in pediatric
      common treatments was 72.4% to cefoperazone/sulbactam, 71.5% to meropenem, 48.4%
      to imipenem, 66.7% to ceftazidime, 49.2% to piperacillin/tazobactam. Absolute
      resistance to ampicillin, cephazolin, cefuroxime and cefotaxime. Multiple-drug
      resistance was still severe, but a decreasing tendency was observed, 90.5% in
      2007, 81.3% in 2008, 51.1% in 2009, 53.8% in 2010, 33.3% in 2011. Pan-drug
      resistance in different years was similar, 12.5% in 2008, 2.2% in 2009, 7.7% in
      2010, 6.7% in 2011. CONCLUSION: The condition of drug resistance of Pseudomonas
      aeruginosa was still rigorous, we should conduct surveillance and prevent abusing
      antibiotics in order to avoid exacerbating drug resistance. We should improve
      testing technique, early and appropriate empirical antibiotics therapy is crucial
      according to clinical experience and antibiotic sensitivity. The effective
      treatment of P. aeruginosa is paramount to prevent multidrug resistance. The use
      of combination therapies for P. aeruginosa infection has been a long-advocated
      practice. To prevent hospital acquired cross infection, health care workers must
      pay close attention to hand sanitation and sterile operation strictly.

PMID- 23158815
TI  - [Clinical manifestations and treatment of early-onset neonatal sepsis: a Chinese
      French comparison].
AB  - OBJECTIVE: To realize the difference between China and France in the clinical
      manifestations, diagnosis and treatment of early-onset neonatal sepsis (EONS) and
      to provide basis to improve the level of our hospital in diagnosing and treating
      this disease. METHOD: Data of 146 cases of EONS were retrospectively analyzed.
      All data were collected from our hospital and a French hospital. Bacterial
      spectrum, clinical manifestations, use of antibacterial drugs, occurrence of
      recording and screening of perinatal risk factors were compared between the two
      hospitals. RESULT: The most common pathogenic bacteria in our hospital were
      coagulase-negative staphylococcus (69.2%) and Escherichia coli (15.4%) while in
      the French Hospital, group B streptococcus (33.3%) and Escherichia coli (33.3%).
      The most common pathogenic bacteria in gastric liquid and peripheral swabs of the
      French hospital were Escherichia coli (33.3%) and group B streptococcus (21.2%).
      Total days of antibacterial use 11.4 +/- 7.2 (d), mean sorts of antibacterial
      drugs for single patient (3.1 +/- 0.9) and proportion of patients who had
      antibacterial drug changes (70.2%) were greater than the French hospital 6.2 +/-
      2.5 (d), 2.2 +/- 0.8(d), (9.9%). Both hospitals were inclined to combine 2
      antibacterial drugs for the first dose (second-generation cephalosporins + semi
      synthetic penicillin in our hospital vs. amoxicillin + amikacin in the French
      hospital). The common second and third line antibacterial drugs in our hospital
      are carbapenems and vancomycin vs. third-generation cephalosporins and vancomycin
      in the French hospital. The rates of occurrence of recording and screening
      perinatal risk factors (chorioamnionitis, maternal fever, prolonged rupture of
      membranes, screening results of vaginal swabs or urinary infection, amniotic
      fluid contamination, prenatal antibacterial prophylaxis, anamnesis of EONS) in
      our hospital was all lower than those of the French hospital. There was no
      significant difference in positive rate of perinatal risk factors between the two
      hospitals. For newborns hospitalized for immediate abnormalities after birth, the
      most common symptom was respiratory distress (96.5% vs. 88.2%). For those
      admitted after a period of time after birth, the proportion of abnormalities was
      different: in our hospital, the most common reasons were respiratory distress
      (44.4%) and lethargy (22.2%) while in the French hospital there were rise of C
      reactive proteins (78.2%) and fever (5.5%). The false negative rate of C reactive
      proteins in diagnosing EONS was not significantly different between the two
      hospitals. CONCLUSION: There was significant difference in diagnosing and
      treating EONS in the two hospitals. Emphasis on screening and recording perinatal
      risk factors, as well as strengthened surveillance on neonates in obstetric
      department could improve the accuracy of early diagnosis of EONS of our hospital.
      Positive attitude to gastric liquid and peripheral swabs culture, with drug
      susceptibility test may help pediatricians better select antibacterial drugs and
      reduce unnecessary changes and the total time of antibiotic use.

PMID- 23158816
TI  - [Carriage of the Pseudomonas aeruginosa virulence factors and prognosis after
      infection].
AB  - OBJECTIVE: To investigate drug-resistance and carriage of virulence factors of
      Pseudomonas aeruginosa (Pa) isolated from children. METHOD: Thirty-eight strains
      of Pa were collected and isolated in pediatric clinic during 2006-2009, and tests
      were undertaken to identify bacteria and susceptibility test was performed using
      VITEK-2 COMPACT GNI and AST-GN13 cards. The virulence factors were confirmed by
      using polymerase chain reaction (PCR) and sequencing. RESULT: All the 38 strains
      of Pa were resistant to ampicillin, ampicillin/sulbactam, cefazolin,
      nitrofurantoin, trimethoprim/sulfamethoxazole, resistance rates were 100%. Except
      for ceftriaxone (60.53%), the resistance rates to other antibiotics were all
      below 16%. PCR test showed that all the 38 strains of Pa carried exotoxin A(toxA)
      and nitric oxide reductase A (norA), however, detective ratio of the other
      virulence factors, exoenzyme Y (exoY) was 84.21% (32/38), exoenzyme S (exoS)
      57.89% (22/38), pyocyanin (pyp) 42.11% (16/38), exoenzyme U (exoU) 34.21%
      (13/38), and 38 strains of Pa did not carry exoenzyme T (exoT) and elastase B
      (lasB) without exception. By analyzing tests, we discovered that 3 pan-drug
      resistant strains of Pa were all combination of exo U+/pyp+, there were 4 strains
      of Pa which were moderately-resistant to imipenem, including exoU+/pyp+/exoY+ (2
      isolates), exo U+/pyp+ (1 isolate), and exoY+/exoS+ (1 isolates). It indicated
      that the drug-resistance rate of exoU+/pyp+ is much higher, compared with exoS+
      and exoY+. Molecular epidemiological detection revealed that 2 of 3 extensive
      resistance strains of Pa were the same clone, but another one had 96.3% of
      homology with them. CONCLUSION: The above mentioned 34.21% of Pa isolated from
      children carried virulence factors toxA, norA, exoS, exoY, pyp and exoU. The
      strains with exoU/pyp had rather high resistance. The strains with pyp had strong
      toxicity, they easily cause generalized infection, the patients with them had
      very high mortality.

PMID- 23158817
TI  - [The experts' consensus on continuous blood purification treatment of severe
      sepsis in children].

PMID- 23158818
TI  - [Infants with acute diarrhea during the clinical nutrition interventions path].

PMID- 23158819
TI  - [Interpretation of the experts' consensus on continuous blood purification
      treatment of severe sepsis in children].

PMID- 23158820
TI  - [Expression and role of urotensin II on the lung of patients with pulmonary
      hypertension with congenital heart disease].
AB  - OBJECTIVE: To observe the expression of urotensin II (UII) on the lung of
      patients with pulmonary hypertension (PH) with congenital heart disease and
      investigate the meaning of this phenomenon. METHOD: Thirty eight patients with
      CHD were divided into three groups according to pulmonary arterial systolic
      pressure (PASP) measured in cardiac catheterization and surgery: normal pulmonary
      pressure group (N group, PASP < 30 mm Hg, n = 10), mild PH group (M group, PASP
      >= 30 mm Hg, n = 15), severe or moderate PH group (S group, PASP >= 50 mm Hg, n =
      13). The expression of UII protein and UII mRNA in pulmonary arterioles were
      measured separately by immunohistochemical (IHC) analysis and in situ
      hybridization (ISH) analysis. RESULT: (1) The results of UIIIHC staining: The UII
      protein expression of group M was higher than that of group N (20.22 +/- 3.58 vs.
      14.34 +/- 2.18, P < 0.01), but less than group S (20.22 +/- 3.58 vs. 28.92 +/-
      3.22, P < 0.05). (2) The results of UIIISH mRNA staining were similar to IHC
      staining, the A value of group M was higher than group N (12.51 +/- 2.02 vs. 8.85
      +/- 1.41, P < 0.05), less than that of group S(12.51 +/- 2.02 vs. 25.35 +/- 4.33,
      P < 0.01). (3) Correlation study: there was a positive correlation between the A
      values of UIIIHC and pulmonary hypertension (r = 0.64, P < 0.01, n = 38), a
      positive correlation between the A values of UIIISH and pulmonary hypertension (r
      = 0.58, P < 0.01, n = 38). CONCLUSION: There was the expression of Urotensin II
      protein and mRNA in the lung of pulmonary hypertension patients with congenital
      heart disease, and these expression may involve the formation of pulmonary
      hypertension of congenital heart disease.

PMID- 23158821
TI  - [Relationship between genetic polymorphism of multidrug resistance 1 gene and the
      risk of childhood acute lymphocytic leukemia].
AB  - OBJECTIVE: To investigate the relationship between genetic polymorphism in exon
      12 C1236T, exon 21 G2677T/A and exon 26 C3435T of the multidrug resistance 1
      (MDR1) gene and the risk of childhood acute lymphocytic leukemia (ALL). METHOD: A
      total of 176 patients with ALL and a cohort of 170 matched healthy subjects were
      included. SNaPshot SNP typing was used to determine the genotypes of MDR1 C1236T,
      G2677T/A, C3435T. Based on the clinical data, the relationship between genetic
      polymorphism of MDR1 and the risk of childhood ALL was analyzed. RESULT: There
      was significant difference in the distribution of genotype of MDR1 C3435T between
      the group of controls and cases. The mutant homozygous TT genotype was found to
      be associated with occurrence of ALL (P = 0.000; OR = 4.504). The data show
      evidence of pairwise linkage disequilibrium between the three common SNPs (C1236T
      G2677T/A-C3435T). The haplotypes of TTT, TGC, CGC and CAC were predominant. The
      haplotype CGT distributed significantly differently between the groups of
      controls and cases (P = 0.034). The frequency of the haplotype TTT/TTT in the
      high risk group was higher than the other groups (P = 0.037). CONCLUSION: The
      present findings suggest that 3435C->T polymorphism in MDR1 gene may be a genetic
      susceptibility factor for ALL. The haplotype of MDR1 (C1236T-G2677T/A-C3435T)
      could be the clinical parameter at diagnosis.

PMID- 23158822
TI  - [Rituximab therapy for severe pediatric systemic lupus erythematosus].
AB  - OBJECTIVE: To analyze the safety and efficacy of anti-CD20 monoclonal antibody in
      treatment of severe pediatric systemic lupus erythematosus (PSLE). METHOD: The
      diagnosis of PSLE was made according to the criteria for the classification of
      systemic lupus erythematosus revised by the American College of Rheumatology in
      1997. Severe cases with PSLE was selected by the following criteria: age <= 16
      years, number of important organs involved > 1, SLEDAI score > 10 points and poor
      response to conventional immunosuppressive treatment. These patients received 2
      doses of 375 mg/m(2) rituximab (RTX), 2 weeks apart. Clinical, laboratory
      findings and drug side effects were recorded at RTX initiation, 2 weeks, 1 month,
      3, 6 and 12 months after infusion. RESULT: A total of 20 patients. Male to female
      ratio was 1:3, were enrolled. They were 5-16 years old. The course of disease was
      (3.0 +/- 2.5) years (range: 1 month-7 years), patients were followed up for 12 -
      36 months [median: (27.0 +/- 7.8) months]. Delirium and cognitive disorders were
      significantly improved in 10 cases of lupus encephalopathy after 1 month. Lupus
      nephritis in children were eased slowly, 14/15 patients with lupus nephritis were
      improved after 2-3 months. Four cases of lupus pneumonia were significantly
      improved within 1 month. Decreased blood cells counts were relieved at 1 month in
      16/18 cases. Cellular immune function was assessed 2 weeks after application of
      anti-CD20 monoclonal antibody; we found B-cell clearance in 19 patients (95%). B
      lymphocyte count of 18 patients (90%) was restored within one year. SLEDAI score
      was reduced obviously. Dose of corticosteroid ranged from (45.0 +/- 4.7) mg/m(2)
      before drug use to (12.0 +/- 2.7) mg/m(2) 12 months later (P < 0.001). After the
      drug use, 5 patients had pneumonia within 6 months; 2 cases who suffered from
      aspergillus pneumonia and Pneumocystis carinii pneumonia respectively were
      severe. They accepted mechanical ventilation and anti-inflammatory support after
      being transferred to the intensive care unit, and their conditions improved at
      last. No death occurred. In 2 patients the disease recurred with B-cell recovery
      after 15 months and 18 months. Administration of another cycle of rituximab
      resulted in remission again in one case but not in the other. CONCLUSION: Anti
      CD20 monoclonal antibody is effective and safe in treatment of severe PSLE. But
      severe infections may occur in some cases. Focusing on prevention and early
      treatment can reduce the probability of adverse reactions.

PMID- 23158823
TI  - [Intraoperative placement of transnasal small intestinal feeding tube during the
      surgery in 5 cases with high position intestinal obstruction and postoperative
      feeding].
AB  - OBJECTIVE: To explore the value of employing the small intestinal feeding tube in
      treating high position intestinal obstruction of newborn infant. METHOD: Five
      newborn infants (3 males and 2 females; 1 premature infant and 4 fully-mature
      infants; 2 had membranous atresia of duodenum, 1 had annular pancreas, and 2 had
      proximal small intestine atresia; 1 infant had malrotation). The duodenal
      membrane-like atresia and the blind-end of small intestine were removed and
      intestinal anastomosis was performed, which was combined with intestinal
      malrotation removal. Before the intestinal anastomosis surgery, the anesthetist
      inserted via nose a 6Fr small intestinal ED tube, made by CREATE MEDIC CO LTD of
      Japan[ REGISTRATION NUMBER: the State Food and Drug Administration-instrument
      (Im.) 2007-NO.2661620]. Twenty-four hours after surgery, abdominal X-ray plain
      film was taken and patients were fed with syrup; 48 hours later, formula milk was
      pumped or lactose-free milk amino acids were given by intravenous injection pump
      through the feeding tube. The amount of milk and fluids was gradually increased
      to normal amount according to the condition. In initial 3 days the intravenous
      nutrition was given and one week after operation, the infants were fed through
      mouth in addition to pumping milk through the tube and stopped infusion. Ten to
      22 days after operation, the tube was removed and the infant patients were
      discharged. RESULT: All the five infants showed that the feeding through the
      nutrition tube was accomplished and the time of venous nutrition was reduced and
      fistula operation was avoided. None of the infants on question was off the tube
      and no jaundice exacerbation was found and the liver function was also found
      normal. At the very beginning, the tube was occasionally blocked by milk vale in
      one infant and after 0.9% sodium chloride solution flushing patency restored.
      After that, the feeding tube was washed once with warm water after feeding. In
      one infant vomiting occurred due to enough oral milk. The photograph of upper
      gastrointestine did not show anastomomotic stricture or fistula, or intestinal
      obstruction. After pulling out the tube, the symptoms disappeared and then the
      patient was discharged. One child was found to have diarrhea with no lactose
      nutrition liquid and given compound lactic bacteria preparations for oral
      administration, the symptom disappeared. In the 5 cases, the shortest hospital
      stay was 10 days and the longest was 22 days, the average stay was 16 days. Three
      to 5 days after operation the weight restored to birth weight, the weight had
      increased, when discharged, to an average of 5.5 g (kg.d). CONCLUSION: The small
      intestinal feeding tube was very effective for the postoperative nutrition
      maintenance of high position intestinal obstruction in newborn infants.

PMID- 23158824
TI  - [A case report of genetic analysis in the OCRL1 gene in Lowe syndrome].

PMID- 23158825
TI  - [Comments on drugs for pediatric use, in essentials for clinical use of drugs
      (the volume of chemical drugs and bioproducts, 2010 edition)].

PMID- 23158826
TI  - [Blood pressure variability in children with autonomous nerve mediated syncope].

PMID- 23158827
TI  - [An overview of the 10(th) International Kawasaki Disease Symposium].

PMID- 23158828
TI  - [The summary of 4(th) Sleep Conference and Pediatric Sleep Medicine Workshop].

PMID- 23158829
TI  - Excess mortality among relocated institutionalized elderly after the Fukushima
      nuclear disaster.

PMID- 23158830
TI  - Feasibility and effectiveness of the implementation of a primary prevention
      programme for type 2 diabetes in routine primary care practice: a phase IV
      cluster randomised clinical trial.
AB  - BACKGROUND: The objective of this study is to perform an independent evaluation
      of the feasibility and effectiveness of an educational programme for the primary
      prevention of type 2 diabetes (DM2) in high risk populations in primary care
      settings, implanted within the Basque Health Service - Osakidetza.
      METHODS/DESIGN: This is a prospective phase IV cluster clinical trial conducted
      under routine conditions in 14 primary health care centres of Osakidetza,
      randomly assigned to an intervention or control group. We will recruit a total
      sample of 1089 individuals, aged between 45 and 70 years old, without diabetes
      but at high risk of developing the condition (Finnish Diabetes Risk Score,
      FINDRISC >= 14) and follow them up for 2 years. Primary health care nursing teams
      of the intervention centres will implement DE-PLAN, a structured educational
      intervention program focused on changing healthy lifestyles (diet and physical
      activity); while the patients in the control centres will receive the usual care
      for the prevention and treatment of DM2 currently provided in Osakidetza. The
      effectiveness attributable to the programme will be assessed by comparing the
      changes observed in patients exposed to the intervention and those in the control
      group, with respect to the risk of developing DM2 and lifestyle habits. In terms
      of feasibility, we will assess indicators of population coverage and programme
      implementation. DISCUSSION: The aim of this study is to provide the scientific
      basis for disseminate the programme to the remaining primary health centres in
      Osakidetza, as a novel way of addressing prevention of DM2. The study design will
      enable us to gather information on the effectiveness of the intervention as well
      as the feasibility of implementing it in routine practice.

PMID- 23158831
TI  - Association of kinase insert domain-containing receptor (KDR) gene polymorphisms
      with idiopathic recurrent spontaneous abortion in Korean women.
AB  - OBJECTIVE: To investigate whether kinase insert domain-containing receptor (KDR)
      gene polymorphisms are risk factors for recurrent spontaneous abortion (RSA) in
      Korean women. DESIGN: Case-control study. SETTING: University hospital.
      PATIENT(S): Three hundred twenty-seven idiopathic RSA patients and 230 controls
      with Korean ethnicity. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): The KDR 
      604T->C (rs2071559), 1192G->A (rs2305948), and 1719A->T (rs1870377) polymorphisms
      were assessed. RESULT(S): KDR -604TC and TC+CC genotypes were more prevalent in
      RSA patients than in controls (adjusted odds ratio [AOR] = 2.091 and 2.076,
      respectively). KDR -604TC+CC/1192GG, -604TC+CC/1719AA, and -604TC+CC/1719TA+TT
      combined genotypes exhibited higher frequencies in RSA patients (AOR = 2.422,
      2.611, and 2.216, respectively). KDR -604C/1192G/1719A, -604C/1192G/1719T, 
      604C/1192G, -604C/1719A, and -604C/1719T haplotype frequencies were higher in RSA
      patients (OR = 1.778, 2.659, 2.089, 1.678, and 1.806, respectively), whereas 
      604T/1192G/1719A, -604T/1192G, and -604T/1719A haplotype frequencies were lower
      in RSA patients (OR = 2.422, 2.611, and 2.216, respectively). No association was
      found between RSA and KDR 1192G->A or 1719A->T. CONCLUSION(S): An association
      between the KDR -604T->C polymorphism and RSA was found in Korean women. Carriers
      of the -604C variant allele were more frequent among RSA patients than among
      controls, suggesting that KDR -604C may confer RSA risk. The association of 1719A
      >T with RSA that was found in Taiwanese Han women was not observed in Korean
      women.

PMID- 23158832
TI  - Knowledge about factors that influence fertility among Australians of
      reproductive age: a population-based survey.
AB  - OBJECTIVE: To explore knowledge about the effects on fertility of age, obesity,
      smoking, and timing of intercourse among Australians of reproductive age. DESIGN:
      Telephone survey of a representative sample of Australians. SETTING: Not
      applicable. PATIENT(S): Australians aged 18 to 45 years who wish to have a child
      or another child now or in the future. INTERVENTION(S): None. MAIN OUTCOME
      MEASURE(S): Knowledge about the effect on fertility of age, obesity, smoking, and
      timing of intercourse. RESULT(S): A total of 462 interviews were conducted. The
      majority of respondents underestimated, by about 10 years, the age at which male
      and female fertility starts to decline. Only one in four correctly identified
      that female fertility starts to decline before age 35, and one in three
      identified that male fertility starts to decline before age 45. Most (59%) were
      aware that female obesity and smoking affect fertility, but fewer recognized that
      male obesity (30%) and smoking (36%) also influence fertility. Almost 40% of
      respondents had inadequate knowledge of when in the menstrual cycle a woman is
      most likely to conceive. CONCLUSION(S): Considerable knowledge gaps about
      modifiable factors that affect fertility were identified. These are targeted in a
      national education campaign to promote awareness of factors that influence
      fertility.

PMID- 23158833
TI  - Effects of pregnancy planning, fertility, and assisted reproductive treatment on
      child behavioral problems at 5 and 7 years: evidence from the Millennium Cohort
      Study.
AB  - OBJECTIVE: To examine the effects of pregnancy planning, time to conception
      (TTC), and assisted reproductive technologies (ART) on child behavior. DESIGN:
      Prospective cohort study. SETTING: Not applicable. PATIENT(S): A total of 12,380
      singletons recruited at 9 months and followed-up at 5 and 7 years. Conceptions
      were divided into "unplanned" (unplanned, unhappy), "mistimed" (unplanned,
      happy), "planned" (planned, TTC <12 months), "subfertile" (planned, TTC >= 12
      months), "ovulation induced" (received clomiphene citrate), and "ART" (IVF or
      intracytoplasmic sperm injection). INTERVENTION(S): None. MAIN OUTCOME
      MEASURE(S): Child behavior (Strengths and Difficulties Questionnaire [SDQ]).
      RESULT(S): Mistimed and unplanned children had higher average SDQ scores at age 5
      and 7 years and were significantly more likely to have a clinically relevant
      behavioral problem compared with the planned group. The ART children had
      significantly higher average SDQ scores at both 5 and 7 years compared with the
      planned group. An increase in clinically relevant behavioral problems was
      observed at 5 years (odds ratio 2.05 [95% confidence interval 0.96, 4.42]) but
      failed to reach statistical significance. No effects were observed in the
      subfertile and ovulation-induced groups. CONCLUSION(S): Unplanned and mistimed
      children exhibit more behavioral problems than their planned peers. Though ART
      children have higher mean total difficulties scores, this did not translate into
      a statistically significant increase in clinically relevant behavioral problems.

PMID- 23158834
TI  - Glycan-based DC-SIGN targeting vaccines to enhance antigen cross-presentation.
AB  - Dendritic cells are the most efficient professional antigen-presenting cells in
      pathogen recognition and play a pivotal role in the control of the immune
      response. Pathogen recognition is ensured by the expression of a vast variety of
      pattern-recognition receptors. Amongst them are C-type lectins, a large family of
      receptors characterized by a domain that - in many cases - mediates calcium
      dependent glycan binding. C-type lectins facilitate antigen uptake for efficient
      processing and presentation and, in some cases, also trigger signaling to
      modulate T cell responses. These properties make C-type lectin receptors ideal
      candidates for the targeting of antigens to dendritic cells for vaccination. DC
      SIGN is a paradigmatic example of C-type lectin receptors on dendritic cells that
      facilitate vaccination strategies. DC-SIGN is highly expressed on immature
      conventional dendritic cells, particularly at the mucosa and the dermis, where
      DCs first encounter pathogens, but also can easily be accessed for vaccination.
      Upon ligand binding, DC-SIGN rapidly internalizes and directs its cargo into the
      endo-lysosomal pathway, which results in MHC-II presentation. But antigens
      targeted to DC-SIGN are also presented efficiently to CD8(+) T cells, suggesting
      there is an additional endocytic route that leads to cross-presentation.
      Simultaneous triggering of DC-SIGN and TLRs results in the modulation of cytokine
      responses and facilitates cross-presentation to enhance CD4(+) and CD8(+) T cell
      responses. Because the glycan specificity of DC-SIGN has been characterized in
      detail, glycans can be used for the targeting of antigens to DCs in a DC-SIGN
      dependent manner. Glycans represent a great advantage over monoclonal antibodies,
      they diminish the risk of side effects, are very small, and their production can
      rely entirely in organic chemistry approaches. Here, we discuss the capacity of
      glycan-based vaccines to enhance antigen-specific CD4(+) and CD8(+) T cell
      responses in human skin and mouse model systems.

PMID- 23158835
TI  - Errorless learning and social problem solving ability in schizophrenia: an
      examination of the compensatory effects of training.
AB  - Compensatory approaches to cognitive rehabilitation in schizophrenia aim to
      improve functioning by bypassing or compensating for impaired areas of cognition.
      At present, there is little empirical evidence that these approaches actually
      compensate for neurocognitive impairments in improving community functioning.
      This study examined the effects of errorless learning (EL), a compensatory
      cognitive rehabilitation approach, on social problem solving ability in
      schizophrenia. The study included 60 outpatients who met DSM-IV criteria for
      schizophrenia or schizoaffective disorder. Participants received a baseline
      battery to assess explicit and implicit memory functioning. Participants were
      stratified according to gender and level of memory functioning and then
      randomized to EL or symptom management training. Training was conducted over two
      days lasting a total of 6h for each group. Assessment of social problem-solving
      ability, using the Assessment of Interpersonal Problem Solving Skills (AIPSS),
      was conducted after completion of training and at a 3-month follow-up without
      further intervention. Results from hierarchical multiple regression and analysis
      of covariance each supported the compensatory effects of training. These findings
      indicate that EL facilitates learning of new skills across varying levels of
      memory impairment. Future efforts may aim to explore the specific neurocognitive
      mechanisms involved in EL.

PMID- 23158836
TI  - The importance of the supervisor for the mental health and work attitudes of
      Australian aged care nurses.
AB  - BACKGROUND: The work attitudes and psychological well-being of aged care nurses
      are important factors impacting on the current and future capacity of the aged
      care workforce. Expanding our understanding of the ways in which the psychosocial
      work environment influences these outcomes is important in order to enable
      organizations to improve the management of human resources in this sector.
      METHODS: Using survey data from a sample of 222 Australian aged care nurses,
      regression analyses were employed to test the relative impact of a range of
      psychosocial work environment variables derived from the demand-control-support
      (DCS) model and organizational justice variables on satisfaction, commitment,
      well-being, and depression. RESULTS: The expanded model predicted the work
      attitudes and well-being of aged care nurses, particularly the DCS components.
      Specifically, demand was related to depression, well-being, and job satisfaction,
      job control was related to depression, commitment, and job satisfaction, and
      supervisor support and interpersonal fairness were related to well-being. The
      contributions of informational and interpersonal justice, along with the main and
      interaction effects of supervisor support, highlight the centrality of the
      supervisor in addressing the impact of job demands on aged care nurses.
      CONCLUSION: Psychosocial variables have utility beyond predicting stress outcomes
      to the work attitudes of nurses in an aged care setting and thus present further
      avenues of research for the retention of nurses and improved patient care.

PMID- 23158837
TI  - Establishing an inflammatory bowel disease practice in an accountable world.

PMID- 23158838
TI  - 3p21.3 tumor suppressor gene RBM5 inhibits growth of human prostate cancer PC-3
      cells through apoptosis.
AB  - BACKGROUND: Recent studies have indicated that the nuclear RNA-binding protein
      RBM5 has the ability to modulate apoptosis and suppress tumor growth. The aim of
      this study is to investigate the expression of RBM5 in human prostate cancer and
      its mechanism of tumor suppression. METHODS: The expression of RBM5 protein in
      cancerous prostatic tissues and normal tissues was examined by IHC. PC-3 cell
      line was used to determine the apoptotic function of RBM5 in vitro. PC-3 cells
      were transiently transfected with pcDNA3.1-RBM5. Cell viability was determined by
      MTT assay. Rhodamine 123 staining and Annexin V analysis were performed to
      observe the apoptotic activity of PC-3 cells overexpressing RBM5. Expression of
      apoptosis-related genes was assessed by western blot. RESULTS: The expression of
      RBM5 protein was significantly decreased in cancerous prostatic tissues compared
      to the normal tissues. PC-3 cells overexpressing RBM5 showed not only significant
      growth inhibition compared with the vector controls, but also dysfunction of
      mitochondrial membrane potential and increased apoptotic activity. To further
      define RBM5 function in apoptotic pathways, we investigated differential
      expression profiles of various BH3-only proteins including Bid, Bad, and Bim, and
      apoptosis regulatory proteins include P53, cleaved caspase9, and cleaved
      caspase3. We found that the expression of both BH3-only proteins and apoptosis
      regulatory proteins was increased in RBM5 transfected cells. CONCLUSION: The
      expression of RBM5 protein was significantly decreased in cancerous prostatic
      tissues, which suggests that RBM5 plays an important role in the pathogenesis of
      prostate cancer. RBM5 may induce the apoptosis of prostate cancer PC-3 cells by
      modulating the mitochondrial apoptotic pathway, and thus RBM5 might be a
      promising target for gene therapy on prostate cancer.

PMID- 23158839
TI  - Bilateral symmetry aspects in computer-aided Alzheimer's disease diagnosis by
      single-photon emission-computed tomography imaging.
AB  - OBJECTIVE: This paper explores the importance of the latent symmetry of the brain
      in computer-aided systems for diagnosing Alzheimer's disease (AD). Symmetry and
      asymmetry are studied from two points of view: (i) the development of an
      effective classifier within the scope of machine learning techniques, and (ii)
      the assessment of its relevance to the AD diagnosis in the early stages of the
      disease. METHODS: The proposed methodology is based on eigenimage decomposition
      of single-photon emission-computed tomography images, using an eigenspace
      extension to accommodate odd and even eigenvectors separately. This feature
      extraction technique allows for support-vector-machine classification and image
      analysis. RESULTS: Identification of AD patterns is improved when the latent
      symmetry of the brain is considered, with an estimated 92.78% accuracy (92.86%
      sensitivity, 92.68% specificity) using a linear kernel and a leave-one-out cross
      validation strategy. Also, asymmetries may be used to define a test for AD that
      is very specific (90.24% specificity) but not especially sensitive. CONCLUSIONS:
      Two main conclusions are derived from the analysis of the eigenimage spectrum.
      Firstly, the recognition of AD patterns is improved when considering only the
      symmetric part of the spectrum. Secondly, asymmetries in the hypo-metabolic
      patterns, when present, are more pronounced in subjects with AD.

PMID- 23158840
TI  - Prevention of transmission of Babesia canis by Dermacentor reticulatus ticks to
      dogs treated with an imidacloprid/flumethrin collar.
AB  - A group of 8 dogs was treated with an imidacloprid/flumethrin collar
      (Seresto((r))) 28 days prior to infestation with adult Dermacentor reticulatus
      ticks, infected with Babesia canis. The ability of the collar to prevent
      transmission of B. canis in the treated group was compared to an untreated
      control group. All 8 dogs in the untreated control group became infected with B.
      canis parasites, which were detected in blood smears as early as day 6 post tick
      application. All control dogs developed clinical signs of babesiosis and were
      rescue-treated with imidocarb dipropionate. These dogs also developed specific B.
      canis antibodies as identified by serology (IFA test) and were confirmed PCR/RLB
      positive. None of the 8 dogs treated with the imidacloprid/flumethrin collar
      became infected with B. canis, which was confirmed by the absence of specific B.
      canis antibodies and babesial DNA as confirmed by PCR/RLB. The collar caused
      96.02% of the ticks to die within 48h post challenge and this increased to 100%
      within 4 days. Although a high percentage of 44% of the Dermacentor ticks were
      infected with B. canis, they were unable to transmit the infection to the treated
      group. Hence, the imidacloprid/flumethrin collar effectively prevented
      transmission of B. canis 1 month after application onto the dogs.

PMID- 23158841
TI  - Use of and factors associated with self-treatment in China.
AB  - BACKGROUND: When an individual is ill or symptomatic, they have the options of
      seeking professional health care, self-treating or doing nothing. In China, some
      studies suggest that the number of individuals opting to self-treat has been
      rapidly increasing in recent years. Therefore, the aim of this study was to
      analyze the trends of and factors related to self-treatment in China. METHODS:
      Self-treatment was measured based the concept and data of the China National
      Health Survey (CNHS), which covers 802,454 individuals. We used CNHS data from
      1993, 1998, 2003, and 2008, and a Multinomial Logit Selection Model to estimate
      the factors influencing the decision to self-treat. RESULTS: The prevalences of
      self-treatment with a recall period of two-weeks were significantly higher in
      urban compared with rural areas (31.2% vs 14.9% in 1993, 43.5% vs 21.4% in 1998,
      47.2% vs 31.4% in 2003, 31.0% vs 25.3% in 2008) in China. Economic (per capita
      income, TV, sanitary water) and individual (education, profession, family
      members, exercise) factors, as well as accessibility to drugs had a positive
      association with the probability of self-treating. Different illness symptoms,
      severity, and duration show a negative association with the probability of self
      treating, showing a degree of rationality in decision-making. Different insurance
      systems were also found to have an effect on self-treatment decision-making.
      CONCLUSIONS: Self-treatment and professional medical services have shared the
      incremental medical needs of residents in recent years in China. Self-perceived
      illness status, economic circumstances, and education play important roles in
      health care decision-making.

PMID- 23158842
TI  - Clinical efficacy of concomitant tibial interventions associated with superficial
      femoral artery interventions in critical limb ischemia.
AB  - BACKGROUND: Combined superficial femoral artery (SFA) and tibial angioplasty (TA)
      are a common treatment for critical limb ischemia. Poor tibial runoff
      significantly compromises durability and clinical effectiveness of SFA
      interventions. The aim of this study is to determine clinical and anatomic
      outcomes of SFA interventions in patients with equally compromised runoff, with
      and without concomitant TA. METHODS: The database of patients undergoing
      endovascular treatment of SFA (1999-2009) was retrospectively queried. Patients
      with poor runoff, scored>10 by modified Society for Vascular Surgery criteria,
      were selected. Preoperative angiograms were reviewed to assess distal popliteal
      and tibial runoff. Kaplan-Meier analyses were performed to assess time-dependent
      outcomes. Factor analyses were performed for time-dependent variables. RESULTS: A
      total of 162 limbs with a runoff score>10 (56% men; average age, 69 years)
      underwent endovascular intervention for symptomatic SFA disease: 61 (54% men)
      underwent TA but the remaining 101 (57% men) did not. The groups were matched for
      age, sex, and SFA anatomy (Trans-Atlantic Inter-Society Consensus II C/D lesions:
      56% no TA vs 62% TA; P=.5). Presenting symptoms were similar between no TA and TA
      groups (rest pain: 40% vs 32%; tissue loss: 60% vs 68%; P=.3). Three-year
      survival favored the TA group (79%+/-5%) vs no TA (68%+/-5%; P=.06). Three-year
      anatomic outcomes in no TA vs TA group, including primary patency (45%+/-6% vs
      63%+/-8%; P=.04), assisted primary patency (55%+/-6% vs 75%+/-7%; P=.03), and
      secondary patency (57%+/-6% vs 77%+/-7%; P=.03) were all superior in the TA
      group. Target vessel revascularization in no TA vs TA (61%+/-6% vs 74%+/-8%;
      P=.002) and target extremity revascularization (42%+/-6% vs 59%+/-8%; P=.06) also
      favored the TA group. However the comparison of no TA vs TA for clinical success
      (39%+/-6% vs 47%+/-8%; P=.6), freedom from recurrent symptoms (59%+/-6% vs 60%+/
      9%; P=.1), amputation-free survival (46%+/-5% vs 63%+/-7%; P=.06), and limb
      salvage at 3 years (63%+/-6% vs 74%+/-7%; P=.6) were similar. CONCLUSIONS: TA in
      patients with poor runoff has a positive effect on SFA anatomic outcomes.
      However, clinical success was not affected. Concomitant TA appears not to add
      clinical benefit to SFA intervention in critical limb ischemia.

PMID- 23158843
TI  - Unsupervised screening for chlamydia and gonorrhoea in backpacker hostels in
      Manly, Sydney.
AB  - Young international backpackers frequently have new sexual partners. We conducted
      a pilot project of unsupervised screening for chlamydia (Chlamydia trachomatis)
      and gonorrhoea (Neisseria gonorrhoeae) by self-collected specimens at two
      backpacker hostels in Manly, Sydney. The median age was 24 years for men and 23
      years for women. A new sexual partner during travel was reported by 94%, of whom
      only 20% always using condoms. The prevalence of chlamydia was 11.9% (14.3% of 35
      men and 10.2% of 49 women). No cases of gonorrhoea were detected. Half of the
      dispensed testing kits went missing or were tampered with, and there was spoilage
      of the receptacle bins, which persisted despite a redesign to a more secure and
      locked box. While populations such as young backpackers may be a priority group
      for sexually transmissible infection screening, we advise caution for projects
      contemplating an unsupervised model.

PMID- 23158844
TI  - Pegylated interferon alpha enhances recovery of memory T cells in e antigen
      positive chronic hepatitis B patients.
AB  - BACKGROUND: Interferons (IFNs) are a group of cytokines commonly used in the
      clinical treatment of chronic hepatitis B (CHB) patients. Their therapeutic
      effects are highly correlated with recovery of host antiviral immunity. Clearance
      of hepatitis B virus (HBV) is mediated partially by activated functional memory T
      cells. The aims of the present study were to investigate memory T cell status in
      patients with different outcomes following pegylated interferon-alpha (IFN-alpha)
      therapy and to identify new biomarkers for predicting antiviral immune responses.
      METHODS: Peripheral blood cells were isolated from 23 CHB patients who were
      treated with pegylated IFN-alpha at week 0 (baseline) and week 24. Co-expression
      of programmed death-1 (PD-1) and CD244 in CD45RO positive T cells, as well as a
      subset of CD127 and CXCR4 positive memory T cells were assessed. In addition,
      perforin, granzyme B, and interferon-gamma (IFN-gamma) expressions were also
      analyzed by flow cytometric analysis after intracytoplasmic cytokine staining
      (ICCS). Peripheral blood mononuclear cells (PBMC) isolated at week 24 were re
      challenged with exogenous HBV core antigen, and the percentage of IFN-gamma
      expression, serum HBV DNA loads, and ALT (alanine aminotransferase) levels were
      evaluated. RESULTS: At week 24, PD-1 and CD244 expression in CD8 memory T cells
      were down-regulated (P < 0.05, P < 0.05, respectively), along with decreased HBV
      DNA loads (P < 0.05), while the expressions of partial effector molecules in CD8
      and CD4 memory T cells was up-regulated (P < 0.05,P < 0.05, respectively),
      especially in the responders. CD127 and CXCR4 were highly expressed in CD8 memory
      T cells after pegylated IFN-alpha treatment (P < 0.05), which was inversely
      correlated with HBV DNA loads (r = -0.47, P = 0.001). The responders had a higher
      IFN-gamma expression in memory T cells than the non-responders did after HBV
      antigen re-stimulation in vitro. CONCLUSION: Pegylated IFN-alpha treatment
      enhanced recovery of memory T cells in CHB patients by down-regulating inhibitory
      receptors and up-regulating effector molecules. The expressions of CXCR4 and
      CD127 in CD8 memory T cell may be used as biomarkers for predicting the outcome
      of treatment.

PMID- 23158845
TI  - Adapting health promotion interventions to meet the needs of ethnic minority
      groups: mixed-methods evidence synthesis.
AB  - BACKGROUND: There is now a considerable body of evidence revealing that a number
      of ethnic minority  groups in the UK and other economically developed countries
      experience disproportionate levels of morbidity and mortality compared with the
      majority white European-origin population. Across these countries, health
      promoting approaches are increasingly viewed as the long-term strategies most
      likely to prove clinically effective and cost-effective for preventing disease
      and improving health outcomes in those with established disease. OBJECTIVES: To
      identify, appraise and interpret research on the approaches employed to maximise
      the cross-cultural appropriateness and effectiveness of health promotion
      interventions for smoking cessation, increasing physical activity and improving
      healthy eating for African-, Chinese- and South Asian-origin populations. DATA
      SOURCES: Two national conferences; seven databases of UK guidelines and
      international systematic reviews of health promotion interventions aimed at the
      general population, including the Clinical Evidence, National Institute for
      Health and Clinical Excellence and Scottish Intercollegiate Guidelines Network
      databases (1950-2009); 11 databases of research on adapted health promotion
      interventions for ethnic minority populations, including BIOSIS, EMBASE and
      MEDLINE (1950-2009); and in-depth qualitative interviews with a purposive sample
      of researchers and health promoters. REVIEW METHODS: Theoretically based, mixed
      methods, phased programme of research that involved user engagement, systematic
      reviews and qualitative interviews, which were integrated through a realist
      synthesis. Following a launch conference, two reviewers independently identified
      and extracted data from guidelines and systematic reviews on the effectiveness of
      interventions for the general population and any guidance offered in relation to
      how to interpret this evidence for ethnic minority populations. Data were
      thematically analysed. Reviewers then independently identified and critically
      appraised studies of adapted interventions and summarised data to assess
      feasibility, acceptability, equity, clinical effectiveness and cost
      effectiveness. Interviews were transcribed, coded and thematically analysed. The
      quantitative and qualitative data were then synthesised using a realist framework
      to understand better how adapted interventions work and to assess implementation
      considerations and prioritise future research. Our preliminary findings were
      refined through discussion and debate at an end-of-study national user engagement
      conference. RESULTS: Initial user engagement emphasised the importance of
      extending this work beyond individual-centred behavioural interventions to also
      include examination of community- and ecological-level interventions; however,
      individual-centred behavioural approaches dominated the 15 relevant guidelines
      and 111 systematic reviews we identified. The most consistent evidence of
      effectiveness was for pharmacological interventions for smoking cessation. This
      body of work, however, provided scant evidence on the effectiveness of these
      interventions for ethnic minority groups. We identified 173 reports of adapted
      health promotion interventions, the majority of which focused on US-based African
      Americans. This body of evidence was used to develop a 46-item Typology of
      Adaptation and a Programme Theory of Adapted Health Promotion Interventions. Only
      nine empirical studies directly compared the effectiveness of culturally adapted
      interventions with standard health promotion interventions, these failing to
      yield any consistent evidence; no studies reported on cost-effectiveness. The 26
      qualitative interviews highlighted the need to extend thinking on ethnicity from
      conventional dimensions to more contextual considerations. The realist synthesis
      enabled the production of a decision-making tool (RESET) to support future
      research. LIMITATIONS: The lack of robust evidence of effectiveness for physical
      activity and healthy-eating interventions in the general population identified at
      the outset limited the comparative synthesis work we could undertake in the
      latter phases. Furthermore, the majority of studies undertaking an adapted
      intervention were conducted within African American populations; this raises
      important questions about the generalisability of findings to, for example, a UK
      context and other ethnic minority groups. Lastly, given our focus on three health
      areas and three populations, we have inevitably excluded many studies of adapted
      interventions for other health topics and other ethnic minority populations.
      CONCLUSIONS: There is currently a lack of evidence on how best to deliver smoking
      cessation, physical activity and healthy eating-related health promotion
      interventions to ethnic minority populations. Although culturally adapting
      interventions can increase salience, acceptability and uptake, there is as yet
      insufficient evidence on the clinical effectiveness or cost-effectiveness of
      these adapted approaches. More head-to-head comparisons of adapted compared with
      standard interventions are warranted. The Typology of Adaptation, Programme
      Theory of Adapted Health Promotion Interventions and RESET tool should help
      researchers to develop more considered approaches to adapting interventions than
      has hitherto been the case. FUNDING: The National Institute for Health Research
      Health Technology Assessment programme.

PMID- 23158846
TI  - Improving medication use in the nursing homes: a European perspective.

PMID- 23158847
TI  - Perspective: Protein supplementation during prolonged resistance type exercise
      training augments skeletal muscle mass and strength gains.

PMID- 23158848
TI  - Having influence: faculty of color having influence in schools of nursing.
AB  - Faculty of color (FOC) play an important role in mentoring students and other FOC
      in schools of nursing. However, the unique nature of mentoring that FOC provide,
      which includes transmission of expert knowledge of the operations of racism in
      nursing academe, is not well understood. Furthermore, the influence FOC have on
      school cultures has not been well documented. To address this gap in knowledge we
      conducted a critical grounded theory study with 23 FOC in predominately Euro
      American schools of nursing. Findings indicate that FOC Having Influence is a key
      process that explicates the influence FOC wield, exposing their work, which is
      often taken for granted, hidden, and, unacknowledged. FOC Having Influence
      occurred in two areas: 1) the survival and success of students and FOC and 2)
      shaping practices in schools of nursing and impacting health in communities.
      Implications for educational practice and future research are presented, based on
      study findings.

PMID- 23158849
TI  - The relationship between shift work and body mass index among Canadian nurses.
AB  - AIM: The aim of this study was to examine the relationship between shift schedule
      and body mass index (BMI) among a sample of Canadian Nurses. BACKGROUND: Higher
      BMI values have been reported for employees working non-standard shifts compared
      to those working a regular daytime schedule. Little is known about the pathways
      through which shift work is associated with higher BMI. METHODS: This study was a
      secondary analysis of a sample from National Survey on the Work and Health of
      Nurses (N=9291). RESULTS: We found a small, but statistically significant,
      difference in BMI scores across shift schedule categories with higher BMI scores
      reported among female nurses working night or mixed shift schedules, compared
      with those working a regular daytime schedule. Adjustment for working conditions
      and employer supported facilities did not attenuate the association between shift
      work and BMI scores. CONCLUSIONS: The potential public health importance of this
      relationship requires further investigation given the small, but statistically
      significant, differences observed in this sample.

PMID- 23158851
TI  - Reducing lameness in dairy herds--overcoming some barriers.
AB  - Incomplete detection, high tolerance of lameness, and shortage of time and labour
      have been identified as barriers to reducing lameness in dairy herds. The effects
      of farmer participation in a project aimed at reducing lameness in dairy cattle
      on these factors were investigated. Over the course of the project farmers'
      detection of lameness improved and tolerance decreased. On farms entering the
      study with lameness prevalence below the median of 35%, improved detection was
      correlated with a reduction in lameness prevalence, but this was not the case for
      farms entering above the median prevalence. Lowered tolerance of lameness was
      correlated with reduced lameness regardless of initial prevalence. A greater
      importance given to lack of time as an initial barrier to progress was correlated
      with a greater reduction in lameness over the course of the project, suggesting
      that farmers who recognised limited time as a barrier were able to overcome this
      to some extent.

PMID- 23158850
TI  - Generation of Trichoderma atroviride mutants with constitutively activated G
      protein signaling by using geneticin resistance as selection marker.
AB  - BACKGROUND: Species of the fungal genus Trichoderma are important industrial
      producers of cellulases and hemicellulases, but also widely used as biocontrol
      agents (BCAs) in agriculture. In the latter function Trichoderma species
      stimulate plant growth, induce plant defense and directly antagonize plant
      pathogenic fungi through their mycoparasitic capabilities. The recent release of
      the genome sequences of four mycoparasitic Trichoderma species now forms the
      basis for large-scale genetic manipulations of these important BCAs. Thus far,
      only a limited number of dominant selection markers, including Hygromycin B
      resistance (hph) and the acetamidase-encoding amdS gene, have been available for
      transformation of Trichoderma spp. For more extensive functional genomics studies
      the utilization of additional dominant markers will be essential. RESULTS: We
      established the Escherichia coli neomycin phosphotransferase II-encoding nptII
      gene as a novel selectable marker for the transformation of Trichoderma
      atroviride conferring geneticin resistance. The nptII marker cassette was stably
      integrated into the fungal genome and transformants exhibited unaltered
      phenotypes compared to the wild-type. Co-transformation of T. atroviride with
      nptII and a constitutively activated version of the Galpha subunit-encoding tga3
      gene (tga3Q207L) resulted in a high number of mitotically stable, geneticin
      resistant transformants. Further analyses revealed a co-transformation frequency
      of 68% with 15 transformants having additionally integrated tga3Q207L into their
      genome. Constitutive activation of the Tga3-mediated signaling pathway resulted
      in increased vegetative growth and an enhanced ability to antagonize plant
      pathogenic host fungi. CONCLUSION: The neomycin phosphotransferase II-encoding
      nptII gene from Escherichia coli proved to be a valuable tool for conferring
      geneticin resistance to the filamentous fungus T. atroviride thereby contributing
      to an enhanced genetic tractability of these important BCAs.

PMID- 23158852
TI  - Staphylococcus aureus Efb protein expression in Nicotiana tabacum and immune
      response to oral administration.
AB  - Staphylococcus aureus (S. aureus) is one of the most widespread agent of diseases
      in humans and animals. In dairy cows, S. aureus is the most frequently isolated
      contagious pathogens in mastitis cases and vaccines are one of the potential
      tools to control the infections, thus decreasing the use of antibiotics. Among
      all the virulence factors produced by S. aureus, extra cellular fibrinogen
      binding protein (Efb) is an important one in the pathogenesis of mastitis. Plants
      are useful bioreactors to produce antigens and the aim of the study was the
      production of Efb in two cultivars of Nicotiana tabacum as a mean to produce
      vaccine against S. aureus in plants. A matrix attachment region (MAR) sequence
      was inserted near the two borders of transfer-DNA in the transformation vector in
      the two possible orientations. The presence of MAR elements in the transformation
      system significantly improved transformation efficiency and Efb protein yield up
      to a 2% level on total soluble protein (TSP). Mice orally immunized with
      transgenic lyophilized leaves produced an antigen-specific immune response.

PMID- 23158853
TI  - Periodontal disease, periodontal treatment and systemic nitric oxide in dogs.
AB  - Thirty-two client-owned dogs treated for periodontal disease were divided in
      group 1 if no periodontitis, group 2 if <=25%, and group 3 if >25% of the teeth
      present were affected with periodontitis. Blood was tested before and 2 weeks
      after periodontal therapy for nitrosyl hemoglobin (HbNO), plasma nitrite/nitrate
      (NOx) and 3-nitrotyrosine (NT) levels. No HbNO was detected in any of the animals
      tested. There was no significant difference in the NOx plasma levels within each
      group or across the groups before and after the treatment, but a noticeable
      increase in NOx plasma levels was observed in group 3 after the treatment. Plasma
      NT was detected in only one third of the animals. NO levels varied greatly across
      individual dogs. The data are suggestive of an overall increase in systemic NO
      response 2 weeks after periodontal treatment in dogs with advanced periodontal
      disease, but the response is greatly individually-dependent.

PMID- 23158854
TI  - [Critical care ensures better patients' safety].

PMID- 23158855
TI  - [The orientation of scholarism plays a determinant role in quality and safety of
      critical care].

PMID- 23158856
TI  - [The effect of stress dose glucocorticoid on patients with acute respiratory
      distress syndrome combined with critical illness-related corticosteroid
      insufficiency].
AB  - OBJECTIVE: To investigate the effect of stress dose glucocorticoid on patients
      with acute respiratory distress syndrome (ARDS) combined with critical illness
      related corticosteroid insufficiency (CIRCI). METHODS: All early ARDS patients
      combined with CIRCI were screened by an adrenal corticotrophic hormone (ACTH)
      test and randomly divided into treatment group (hydrocortisone 100 mg
      intravenous, 3 times/day, consecutively for 7 days, n = 12) and control group
      (equivalent normal saline, n = 14). General clinical data, changes of arterial
      blood gas, hemodynamics and respiratory mechanics were observed and recorded at
      admission and at 7 days after treatment. Ventilator-free and shock-free days, ICU
      stay within 28 days after admission were recorded and 28-day mortality was used
      as judge prognosis index. RESULTS: CIRCI rate in 45 early ARDS patients was 57.8%
      (26 patients), and the shock rate was markedly higher in ARDS patients with CIRCI
      than patients without CIRCI (46.2% vs 5/19). There were no significant
      differences in baseline parameters, oxygenation and illness severity between the
      treatment and control groups, except for markedly lower lactic level in the
      treatment group [2.7(1.2, 3.9) mmol/L vs 4.6(2.5, 6.3) mmol/L, P < 0.05]. After 7
      days of treatment, PaO2/FiO2 markedly increased, while heart rate obviously
      decreased in the both groups. Compared with the control group, survival time of
      patients was significantly longer and shock rate of the patients was markedly
      lower in treatment group within 28 days (5/12 vs 10/14, P < 0.05). The 28-day
      mortality, which were adjusted by baseline arterial lactic, was lower in the
      treatment group (2.6/12) than in the control group (5.8/14) while with no
      significant difference (P > 0.05). There was no significant difference in
      complication incidence between the two groups. CONCLUSION: Stress dose
      glucocorticoid could reduce shock incidence and prolong survival time, and has a
      tendency of lower 28-day mortality in early ARDS patients combined with CIRCI.

PMID- 23158857
TI  - [Titrating positive end-expiratory pressure after recruitment maneuver according
      to end-tidal carbon dioxide and its related indicators in acute respiratory
      distress syndrome dog model].
AB  - OBJECTIVE: To investigate the relationship between end-tidal carbon dioxide with
      its related indicators and ventilation/perfusion of the acute respiratory
      distress syndrome (ARDS) lung, and to explore a feasible way to titrate positive
      end-expiratory pressure (PEEP) in clinical practice. METHODS: Five mixed-breed
      dogs with oleic acid lung injury model were mechanically ventilated at a serial
      PEEP trial including a recruitment maneuver (RM) before each PEEP level changed.
      The value of blood dynamics, end-tidal carbon dioxide partial pressure (PetCO2)
      and arterial carbon dioxide pressure under different PEEP levels were recorded.
      Arterial end-tidal carbon dioxide gradient (Pa-etCO2) and dead space fraction
      (Vd/Vt%) were calculated. All dogs received CT scan. Lung volume under different
      pressure levels, and ratio and volume of alveolar closing pressure, collapsed
      alveoli, sufficiently and insufficiently ventilated alveoli were obtained.
      Alveolar opening and closing analysis were performed by non-liner regression
      equation. RESULTS: The mean pressure when Vd/Vt% obtained lowest level were (11.2
      +/- 4.4) cm H2O (1 cm H2O = 0.098 kPa), which had no significant difference when
      compared to alveolar closing pressure [(11.5 +/- 3.2) cm H2O](P > 0.05). The
      fraction of insufficiently ventilated and collapsed alveoli showed a significant
      linear correlation with the Vd/Vt% when PEEP was lower than P(min) (r = 0.632, P
      = 0.004). There was a linear correlation between the Vd/Vt% and the fraction of
      over-distended alveoli when PEEP was higher than P(min) (r = 0.770, P = 0.001).
      CONCLUSIONS: Closing pressure is in accordance with PEEP level after RM having
      reached the best ventilation/circulation ratio. The characteristics of lung
      collapse can be revealed by Vd/Vt% changes after RM. To titrate PEEP for the
      lowest Vd/Vt% after RM may be a feasible way to match the best ventilation and
      circulation effects of PEEP.

PMID- 23158858
TI  - [The association of insulin resistance, blood pressure variability and severity
      of acute coronary syndrome].
AB  - OBJECTIVE: To investigate the association of insulin resistance (IR), blood
      pressure variability (BPV) and the severity of acute coronary syndrome (ACS), and
      assess the effect of percutaneous coronary intervention (PCI) on recent
      prognosis. METHODS: A total of 260 patients diagnosed as ACS and hospitalized in
      our department of cardiology from December 2009 to December 2010 were enrolled in
      the study. There were 93 cases of unstable angina pectoris(UAP), 84 of non ST
      segment elevation myocardial infarction and 83 of unstable angina pectoris. The
      subjects were divided into two groups according to 24 hour systolic blood
      pressure coefficient of variability (24 h SBP-CV) levels: high-CV group (24 h SBP
      CV > 11.5, n = 130) and low-CV group(24 h SBP-CV < 11.5, n = 130). The
      differences in HOMA-IR and the severity of coronary artery diseases between the
      two groups were compared. The association of major adverse cardiac events within
      6 months after PCI treatment, and IR as well as BPV was analyzed. RESULTS:
      Compared with the low-CV group, ACS patients in the high-CV group had obviously
      higher HOMA-IR levels (5.7 +/- 1.2 vs 4.0 +/- 1.4, P < 0.01), more multivessel
      diseases (49.2% vs 33.3%, P < 0.05) and B2/C type coronary diseases (48.5% vs
      27.7%, P < 0.01), and higher coronary Gensini scores (59.7 +/- 17.5 vs 43.8 +/-
      18.6, P < 0.01). Multi-factors logistic regression analysis indicated that both
      24 h BPV-CV and IR were independent predictors for MACE incidence within 6 months
      after undergone PCI (P < 0.05 or P < 0.01). CONCLUSIONS: IR and BPV were
      obviously associated with the severity of coronary artery diseases in ACS
      patients. IR and 24 h BPV-CV were valuable in predicting recent prognosis of ACS
      patients.

PMID- 23158859
TI  - [A retrospective analysis of azathioprine in the treatment of 24 patients with
      refractory ulcerative colitis].
AB  - OBJECTIVE: To evaluate the efficacy and safety of azathioprine (AZA) in the
      treatment of refractory ulcerative colitis (UC). METHODS: Retrospective analysis
      of the clinical improvement, endoscopic improvement and mucosal healing rate,
      inflammation marker improvement after AZA administration and its safety in 24
      refractory UC patients were performed, who were recruited between January 2007
      and December 2011 in West China Hospital, Sichuan University, China. RESULTS:
      Twenty-four patients were enrolled, with a median age of 36 years old and a
      median course of 4 years. Among them, 14 cases were moderate UC and 10 cases were
      severe UC. The patients were treated with AZA in a dose of (1.23 +/- 0.34) mg*kg(
      1)*d(-1) from 7 weeks to 42 months. Efficacy was judged by Mayo disease activity
      index. At 3 months, 6 months and 1 year after treatment, the effective rates were
      73.9% (17/23), 81.8% (18/22) and 14/16 respectively, and the remission rates were
      17.4% (4/23), 54.5% (12/22) and 12/16 respectively. Both ESR and C reactive
      protein level after treatment for 6 months and 1 year were significantly lower
      than those before treatment [(9.3 +/- 8.9) mm/1h, (10.9 +/- 7.3) mm/1h vs (22.3
      +/- 10.7) mm/1h; 2.5(1.0-22.3) mg/L, 2.3(1.0-28.0) mg/L vs 18.4(3.6-137.0) mg/L;
      all P < 0.05]. Corticosteroid withdrawal rates at 3 months and 1 year after AZA
      treatment were 16/18 and 15/16, respectively. At 6 months and 1 year after AZA
      treatment, the endoscopic improvement rates were 85.7% (18/21) and 13/15
      respectively; the endoscopic remission rates were 61.9% (13/21) and 11/15
      respectively; and the mucosal healing rates were 61.9% (13/21) and 11/15
      respectively. Adverse effects were occurred in 8 patients. Leukopenia was the
      most common adverse effect, followed by liver function injury, alopecia and
      epigastric discomfort. CONCLUSIONS: AZA is effective in the treatment of
      refractory UC patients with a low dose of (1.23 +/- 0.34) mg*kg(-1)*d(-1),
      especially in the steroid withdrawing, maintaining remission and mucosal healing
      without severe adverse effects.

PMID- 23158860
TI  - [A noninvasive diagnostic model of liver fibrosis using serum markers in primary
      biliary cirrhosis].
AB  - OBJECTIVE: To verify and assess diagnostic value of noninvasive diagnostic model
      of liver fibrosis in primary biliary cirrhosis (PBC) based on conventional
      laboratory markers. METHODS: Seventy-three patients with PBC diagnosed by liver
      biopsy between January 2003 and June 2011 in Beijing Friendship Hospital, Capital
      Medical University were recruited in this study. Correlation analysis and
      logistic regression analysis between the conventional laboratory markers and
      histology stages were assessed. A liver fibrosis diagnostic model was established
      based upon aforementioned biomarkers and verified by its sensitivity and
      specificity for predicting the liver fibrosis. RESULTS: The predictive model (H
      index) consisting of five conventional laboratory markers, i.e., platelet count,
      serum cholinesterase, albumin, HDL-C and prothrombin time activity, could predict
      advanced fibrosis (stages III-IV) with an AUC(ROC) of 0.861. The sensitivity of
      predicting the absence of advanced fibrosis using H index < -2.20 was 96.6% and
      the specificity of predicting the presence of advanced fibrosis using H index >
      0.41 was 93.2%. CONCLUSION: The established noninvasive diagnostic model
      consisting of five laboratory markers could accurately distinguish pathological
      changes of early stage PBC (stages I-II) from advanced stage PBC (stages III-IV).

PMID- 23158861
TI  - [The clinical characteristics of patients with thymoma-associated myasthenia
      gravis].
AB  - OBJECTIVE: To investigation the clinical characteristics in myasthenia gravis
      (MG) patients with thymomas. METHODS: A total of 856 MG patients admitted to the
      department during 2008.7 - 2010.12 were reviewed retrospectively. The patients
      with MG were divided into two groups based on thymic pathology, which were 162
      cases with thymoma and 694 cases without thymoma. We compared the different
      clinical features including the gender, age of onset, MG symptoms and the
      incidence rate of myasthenia crisis. And the relationship between the WHO types,
      Maosaoka stages of thymoma and the severe of MG was also studied. RESULTS: The
      percentage of thymoma-associated MG patients was 18.9 percent of hospitalized MG
      patients at the same period. Of the 162 thymoma-associated patients, 94 were male
      and 68 were female, with a ratio of 1.38:1 and a mean age of (42.9 +/- 12.4)
      years old. Thymoma was more frequent in middle-old aged patients than in
      children. Compared with non-thymoma MG, more thymomatous patients showed
      generalised MG, but not only ocular muscles weakness (90.1% vs 62.4%, P < 0.001).
      There were significant differences of the incidence rate of myasthenic crisis in
      the two groups (14.8% vs 2.3%). (2) WHO type B2 and Maosaoka I, II thymoma were
      the commonest types among all potentially MG-associated thymoma. No differences
      of Osserman MG classification was found in thymomatous patients with different
      pathologic changes. CONCLUSIONS: The thymomatous MG patients had its distinctive
      clinical features: thymomas occurred in about 19.7% of MG patients with more men
      than women, more common in generalized, higher incidence of myasthenia crisis,
      with B2 type thymic pathology and Maosaoka I, II stages. No correlation was found
      between pathologic and clinical stages.

PMID- 23158862
TI  - [The diagnostic values of Wells score and modified Geneva score for pretesting
      acute pulmonary embolism: a prospective study].
AB  - OBJECTIVE: To assess the diagnostic predictive value of Wells score and modified
      Geneva score for acute pulmonary embolism by prospective case series and to
      explore a more suitable scoring system for Chinese population. METHODS: All the
      patients suspected of pulmonary embolism (PE) and received CT pulmonary
      angiography (CTPA) were enrolled consecutively in Fuxing Hospital, Capital
      Medical University, China, from June 2009 to August 2011. Before CTPA test or on
      condition that test results were unknown, clinical scoring was assessed
      prospectively by the Wells score and the modified Geneva score. The probability
      of PE in each patient was assessed and the patients were divided into low,
      moderate and high probability groups according to the clinical scores. The result
      of CTPA was used as the diagnostic gold standard for PE. Diagnostic accuracy in
      each group was analyzed. The predictive accuracy of both scores was compared by
      AUC(ROC) curve. RESULTS: A total of 139 patients met our enrollment criteria and
      117 eligible patients entered our study at last. PE was diagnosed in 47 patients
      by CTPA with an overall prevalence of 40.2%.Prevalence of PE in the low, moderate
      and high pretest probability groups assessed by the Wells score and by the
      simplified modified Geneva score were 7.1% (3/42), 42.9% (21/49), 88.5% (23/26)
      and 10.0% (3/30), 48.1% (37/77), 7/10, respectively. AUC(ROC) curves for the
      Wells score and the simplified modified Geneva score were 0.872 (95%CI 0.810 -
      0.933) and 0.734 (95%CI 0.643 - 0.825) respectively, with a significant
      difference (P = 0.005). CONCLUSION: The Wells score is more accurate for clinical
      predicting acute PE than the modified Geneva score.

PMID- 23158863
TI  - [An analysis of risk factors for ischemic stroke of different age and gender].
AB  - OBJECTIVE: To compare distribution difference in risk factors of patients with
      first-ever ischemic stroke (IS) of different age and gender. METHODS: A total of
      1027 patients admitted to the neurological department in Shanghai Renji Hospital
      with first-ever IS were recruited and divided into young adult group (< 50 years
      old), middle-aged group (50 - 80 years old), and very old group (> 80 years old)
      according to their ages. Risk factor analysis included history of smoking, high
      alcohol consumption, hypertension (HT), diabetes mellitus (DM), heart diseases,
      atrial fibrillation (AF) and family history of cardiovascular diseases. RESULTS:
      Female patients were globally older than male patients (71.1 vs 65.7, P < 0.001)
      at the first attack of IS and having higher prevalence of DM (26.8% vs 19.2%, P =
      0.004), heart diseases (28.8% vs 19.2%, P < 0.001) and AF (7.6% vs 3.9%, P =
      0.009). However, female patients were less likely to drink heavily (1.0% vs
      31.6%, P < 0.001) or smoke (4.4% vs 59.9%, P < 0.001) than the male patients. The
      rates of smoking and heavy drinking in young adult group were higher than that in
      other two groups. Patients in very old group had higher prevalence of heart
      diseases and AF but lower proportion of positive family cardiovascular diseases
      history than patients in other two groups. HT and DM were equally frequent among
      three groups. In young adult group, female patients were more likely to have
      heart diseases and family history of heart diseases (P = 0.015 and P = 0.048). In
      middle-old group, HT, DM, heart disease and AF were more common in women than in
      men (P = 0.021, P = 0.004, P = 0.001 and P = 0.039). CONCLUSION: There are
      differences in risk factor distribution in patients with first-ever IS of
      different age and gender. Therefore, screening and health education should be
      performed in allusion to different risk factors.

PMID- 23158864
TI  - [The role of CXCR3 and its ligand I-TAC in the pathogenesis of immune
      thrombocytopenic purpura].
AB  - OBJECTIVE: To investigate the roles of the chemokine receptor CXCR3 and its
      ligand I-TAC in the pathogenesis of immune thrombocytopenic purpura (ITP).
      METHODS: A total of 48 ITP patients were enrolled in this study: 30 with newly
      diagnosed or relapse ITP and 18 in remission after treatment, and 24 healthy
      volunteers were as controls. IFNgamma and I-TAC in plasma were detected by ELISA.
      The mRNA expression of CXCR3 in the peripheral blood mononuclear cells (PBMNCs)
      was determined by quantitative RT-PCR. RESULTS: The IFNgamma level in the plasma
      of ITP patients before the treatment was obviously increased than those in the
      remission group and controls [(71.45 +/- 17.62) ng/L vs (36.94 +/- 14.86) ng/L
      and (25.28 +/- 12.85) ng/L, all P < 0.05] and those in the remission group was
      higher than in the controls (P < 0.05). In contrast, there were no statistic
      differences of the levels of I-TAC among the three groups [(455.56 +/- 144.70)
      ng/L, (488.24 +/- 164.70) ng/L and (382.97 +/- 167.43) ng/L, P > 0.05]. Both ITP
      patients before the treatment and remission groups expressed more CXCR3 mRNA
      [6.76 (3.03, 37.00), 1.76 (0.45, 14.18) vs 0.12 (0.04, 0.28), P < 0.05]. After
      effective therapy, CXCR3 mRNA expression decreased, while it was still higher
      than that in the controls. CONCLUSIONS: Our data demonstrate that Th1 cytokine
      (IFNgamma) dominance is reflected in ITP. Simultaneously, the CXCR3(+) cell may
      play a role in cell-mediated immunity through chemotaxis in ITP.

PMID- 23158865
TI  - [The effects of insulin and gliclazide therapy on endoplasmic reticulum stress
      and insulin sensitivity in liver of type 2 diabetic rats].
AB  - OBJECTIVE: To investigate the effect of insulin and gliclazide therapy on
      endoplasmic reticulum (ER) stress and insulin sensitivity in the liver of type 2
      diabetic rats. METHODS: A high fat diet plus a low-dose of streptozotocin was
      implemented to create a type 2 diabetic rats which were randomly divided into
      diabetes mellitus (DM) group, insulin treatment (INS) group and gliclazide
      treatment (GT) group; and healthy rats were as normal control group. Diabetic
      rats in INS and GT groups were given neutral protamine hagedorn (NPH) insulin and
      gliclazide respectively for 3 weeks. Protein expression levels of immunoglobulin
      binding protein (Bip), spliced X-box binding protein 1 (XBP-1s), phosphorylated c
      Jun on serine 73 (p-c-Jun), phosphorylated insulin receptor substrate 1 on serine
      307 (p-IRS-1), and glucose-6-phosphatase (G6Pase) in liver homogenate were
      detected by Western blotting. RESULTS: Compared with the normal rats, Bip and XBP
      1s in the DM group were up-regulated (0.28 +/- 0.07 vs 0.90 +/- 0.10 for Bip;
      0.41 +/- 0.07 vs 0.95 +/- 0.07 for XBP-1s; both P < 0.01); p-c-Jun (0.59 +/- 0.18
      vs 1.94 +/- 0.03), p-IRS-1 (1.73 +/- 0.18 vs 5.32 +/- 0.22) and G6Pase(0.11 +/-
      0.01 vs 0.45 +/- 0.01) were increased (all P values < 0.01). In the INS group,
      all of aforementioned changes were reversed (0.90 +/- 0.10 vs 0.25 +/- 0.04 for
      Bip; 0.95 +/- 0.07 vs 0.47 +/- 0.01 for XBP-1s; 1.94 +/- 0.03 vs 0.50 +/- 0.10
      for p-c-Jun; 5.32 +/- 0.22 vs 1.59 +/- 0.32 for p-IRS-1; 0.45 +/- 0.01 vs 0.15 +/
      0.02 for G6Pase, all P values < 0.01). In the GT group, all of aforementioned
      changes were also attenuated (0.90 +/- 0.10 vs 0.53 +/- 0.02 for Bip; 0.95 +/-
      0.07 vs 0.78 +/- 0.02 for XBP-1s; 1.94 +/- 0.03 vs 1.33 +/- 0.11 for p-c-Jun;
      5.32 +/- 0.22 vs 3.13 +/- 0.02 for p-IRS-1; 0.45 +/- 0.01 vs 0.25 +/- 0.01 for
      G6Pase, all P values < 0.05). Furthermore, all of aforementioned protein levels
      were down-regulated more obviously in the INS group comparing to the GT group
      (all P values < 0.01). CONCLUSIONS: Both insulin and gliclazide therapy could
      relieve ER stress and c-Jun N-terminal kinase activity and improved insulin
      sensitivity. The effect of insulin on Bip, XBP-1s, p-c-Jun, p-IRS-1 and G6Pase
      protein expressions is more obvious than that of gliclazide, which indicates
      besides lowering glucose, insulin might have protective effects of anti
      inflammation, anti-oxidative stress or stimulation of lipid redistribution.

PMID- 23158866
TI  - Effects of vitamin B12 supplementation on cognition, depression, and fatigue in
      patients with lacunar stroke.

PMID- 23158867
TI  - [Hypotension and ST-segment depression in response to disulfiram-ethanol].

PMID- 23158868
TI  - Exhaled breath condensate pH in mechanically ventilated patients.
AB  - OBJECTIVES: In this prospective clinical trial we aimed to answer if spontaneous
      exhaled breath condensate (EBC) in the trap of the expiratory arm of the
      ventilator could replace EBC collected by coolant chamber standardized with Argon
      as an inert gas. Second, if EBC pH could predict ventilator associated pneumonia
      (VAP) and mortality. PATIENTS: We included 34 critically ill patients (males =
      26), aged = 54.85 +/- 19.86 (mean +/- SD) yrs, that required mechanical
      ventilation due to non-pulmonary direct cause (APACHE II score = 23.58 +/- 14.7;
      PaO(2)/FiO(2) = 240.00 +/- 98.29). SETTING: ICU with 9 beds from a regional
      teaching hospital. INTERVENTION AND RESULTS: The patients were followed up until
      development of VAP, successful weaning or death. There were significant
      differences between mean EBC pH from the 4 procedures with the exception of
      spontaneous EBC de-aerated with Argon (n = 79; 6.74 +/- 0.28) and coolant chamber
      deaerated with Argon (n = 79; 6.70 +/- 0.36; p = NS by Tukey's Multiple
      Comparison Test). However, none of the procedures were extrapolated between each
      other according to Bland & Altman method. The mean EBC pH from the trap without
      Argon was 6.50 +/- 0.28. From the total of 34 patients, 22 survived and were
      discharged and 12 patients died in the ICU. CONCLUSION: Spontaneous EBC pH could
      not be extrapolated to EBC pH from coolant chamber and it did not change in
      subjects who dead, neither subject with VAP in comparison with baseline data. The
      lack of other biomarker in EBC and the lack of a control group determinate the
      need for further studies in this setting.

PMID- 23158869
TI  - Noninvasive mechanical ventilation in chronic obstructive pulmonary disease and
      in acute cardiogenic pulmonary edema.
AB  - Noninvasive ventilation (NIV) with conventional therapy improves the outcome of
      patients with acute respiratory failure due to hypercapnic decompensation of
      chronic obstructive pulmonary disease (COPD) or acute cardiogenic pulmonary edema
      (ACPE). This review summarizes the main effects of NIV in these pathologies. In
      COPD, NIV improves gas exchange and symptoms, reducing the need for endotracheal
      intubation, hospital mortality and hospital stay compared with conventional
      oxygen therapy. NIV may also avoid reintubation and may decrease the length of
      invasive mechanical ventilation. In ACPE, NIV accelerates the remission of
      symptoms and the normalization of blood gas parameters, reduces the need for
      endotracheal intubation, and is associated with a trend towards lesser mortality,
      without increasing the incidence of myocardial infarction. The ventilation
      modality used in ACPE does not affect the patient prognosis. 

PMID- 23158870
TI  - Role of circulating soluble chemokines in septic shock.
AB  - PURPOSE: Chemokines are a large superfamily of small proteins that function not
      only in leukocyte trafficking, but are also necessary for linkage between innate
      and adaptive immunity. Little is known about their role in septic shock. We
      hypothesized that serum levels of the most important chemokines are related to
      organ failure, disease severity and outcome. DESIGN: A prospective observational
      study was carried out. SETTING: Surgical-clinical Intensive Care Unit. PATIENTS:
      Ninety-two patients diagnosed with septic shock using international criteria.
      Forty patients were excluded due to acquired immunity disturbances. Samples from
      36 healthy controls were also analyzed. INTERVENTIONS: None. RESULTS: In 46% of
      the patients who suffered acute respiratory distress syndrome (ARDS), IL-8 levels
      were higher than in patients without ARDS (499.9+/-194.1 vs. 190.8+/-91.7 pg/ml;
      P=.039). This molecule was also higher in 36% of the patients with sepsis-induced
      acute renal failure (ARF) (453.3+/-181.6 vs. 201.3+/-95.9 pg/ml; P=.049).
      Coagulopathy was found in 19% of the septic shock patients with elevated serum IL
      8 levels (635.8+/-292.3 vs. 218.7+/-87.0 pg/ml; P=.010), elevated MIP-1alpha
      (91.4+/-27.3 vs. 58.8+/-11.1 pg/ml; P=.044), and low circulating RANTES levels
      (8162.2+/-6321.0 vs. 18781.8+/-11.1 pg/ml; P=.027). No significant differences
      were found between survivors and non-survivors at any time of follow-up.
      CONCLUSIONS: Upon admission to the ICU, IL-8 is a reliable biomarker of sepsis
      induced AFR, ARDS and coagulopathy. Altered circulating MIP-1alpha and RANTES
      levels are also found in patients with septic shock and coagulopathy. However,
      chemokines do not appear to be good biomarkers of mortality in septic shock.

PMID- 23158872
TI  - A needs analysis method for land-use planning of illegal dumping sites: a case
      study in Aomori-Iwate, Japan.
AB  - Land use at contaminated sites, following remediation, is often needed for
      regional redevelopment. However, there exist few methods of developing
      economically and socially feasible land-use plans based on regional needs because
      of the wide variety of land-use requirements. This study proposes a new needs
      analysis method for the conceptual land-use planning of contaminated sites and
      illustrates this method with a case study of an illegal dumping site for
      hazardous waste. In this method, planning factors consisting of the land-use
      attributes and related facilities are extracted from the potential needs of the
      residents through a preliminary questionnaire. Using the extracted attributes of
      land use and the related facilities, land-use cases are designed for selection
      based conjoint analysis. A second questionnaire for respondents to the first one
      who indicated an interest in participating in the second questionnaire is
      conducted for the conjoint analysis to determine the utility function and
      marginal cost of each attribute in order to prioritize the planning factors to
      develop a quantitative and economically and socially feasible land-use plan.
      Based on the results, site-specific land-use alternatives are developed and
      evaluated by the utility function obtained from the conjoint analysis. In this
      case study of an illegal dumping site for hazardous waste, the uses preferred as
      part of a conceptual land-use plan following remediation of the site were (1)
      agricultural land and a biogas plant designed to recover energy from biomass or
      (2) a park with a welfare facility and an athletic field. Our needs analysis
      method with conjoint analysis is applicable to the development of conceptual land
      use planning for similar sites following remediation, particularly when added
      value is considered.

PMID- 23158873
TI  - A dynamic optimization model for solid waste recycling.
AB  - Recycling is an important part of waste management (that includes different kinds
      of issues: environmental, technological, economic, legislative, social, etc.).
      Differently from many works in literature, this paper is focused on recycling
      management and on the dynamic optimization of materials collection. The developed
      dynamic decision model is characterized by state variables, corresponding to the
      quantity of waste in each bin per each day, and control variables determining the
      quantity of material that is collected in the area each day and the routes for
      collecting vehicles. The objective function minimizes the sum of costs minus
      benefits. The developed decision model is integrated in a GIS-based Decision
      Support System (DSS). A case study related to the Cogoleto municipality is
      presented to show the effectiveness of the proposed model. From optimal results,
      it has been found that the net benefits of the optimized collection are about 2.5
      times greater than the estimated current policy.

PMID- 23158871
TI  - Juvenile-onset motor neuron disease caused by novel mutations in beta
      hexosaminidase.
AB  - A 12 year-old female presented with a seven-year history of progressive muscle
      weakness, atrophy, tremor and fasciculations. Cognition was normal. Rectal biopsy
      revealed intracellular storage material and biochemical testing indicated low
      hexosaminidase activity consistent with juvenile-onset G(M2)-gangliosidosis.
      Genetic evaluation revealed compound heterozygosity with two novel mutations in
      the hexosaminidase beta-subunit (c.512-3 C>A and c.1613+15_1613+18dup). Protein
      analysis was consistent with biochemical findings and indicated only a small
      portion of beta-subunits were properly processed. These results provide
      additional insight into juvenile-onset G(M2)-gangliosidoses and further expand
      the number of beta-hexosaminidase mutations associated with motor neuron disease.

PMID- 23158874
TI  - The performance of Electro-Fenton oxidation in the removal of coliform bacteria
      from landfill leachate.
AB  - Leachate pollution is one of the main problems in landfilling. Researchers have
      yet to find an effective solution to this problem. The technology that can be
      used may differ based on the type of leachate produced. Coliform bacteria were
      recently reported as one of the most problematic pollutants in semi-aerobic
      (stabilized) leachate. In the present study, the performance of the Electro
      Fenton process in removing coliform from leachate was investigated. The study
      focused on two types of leachate: Palau Borung landfill leachate with low
      Coliform content (200 MPN/100 m/L) and Ampang Jajar landfill leachate with high
      coliform content (>24 * 10(4)MPN/100 m/L). Optimal conditions for the Electro
      Fenton treatment process were applied on both types of leachate. Then, the
      coliform was examined before and after treatment using the Most Probable Number
      (MPN) technique. Accordingly, 100% removal of coliform was obtained at low
      initial coliform content, whereas 99.9% removal was obtained at high initial
      coliform content. The study revealed that Electro-Fenton is an efficient process
      in removing high concentrations of pathogenic microorganisms from stabilized
      leachate.

PMID- 23158875
TI  - Study concerning the recovery of zinc and manganese from spent batteries by
      hydrometallurgical processes.
AB  - Used batteries contain numerous metals in high concentrations and if not disposed
      of with proper care, they can negatively affect our environment. These metals
      represent 83% of all spent batteries and therefore it is important to recover
      metals such as Zn and Mn, and reuse them for the production of new batteries. The
      recovery of Zn and Mn from used batteries, in particular from Zn-C and alkaline
      ones has been researched using hydrometallurgical methods. After comminution and
      classification of elemental components, the electrode paste resulting from these
      processes was treated by chemical leaching. Prior to the leaching process the
      electrode paste has been subjected to two washing steps, in order to remove the
      potassium, which is an inconvenient element in this type of processes. To
      simultaneously extract Zn and Mn from this paste, the leaching method in alkaline
      medium (NaOH solution) and acid medium (sulphuric acid solution) was used. Also,
      to determine the efficiency of extraction of Zn and Mn from used batteries, the
      following variables were studied: reagents concentration, S/L ratio, temperature,
      time. The best results for extraction yield of Zn and Mn were obtained under acid
      leaching conditions (2M H2SO4, 1h, 80 degrees C).

PMID- 23158876
TI  - Laparoscopy-assisted versus open D2 radical gastrectomy for advanced gastric
      cancer without serosal invasion: a case control study.
AB  - BACKGROUND: The application of laparoscopic surgery for advanced gastric cancer
      (AGC) remains questionable on account of technical difficulty of D2
      lymphadenectomy, and there has been few large-scale follow-up results regarding
      the oncological adequacy of laparoscopic surgery compared with that of open
      surgeries for AGC. The aim of this study is to evaluate technical feasibility and
      oncological efficacy of laparoscopy-assisted gastrectomy (LAG) for advanced
      gastric cancer without serosal invasion. METHODS: From January 2008 to December
      2012, 1114 patients with gastric cancer underwent D2 gastrectomy, including 336
      T2 and T3 patients in term of depth of invasion. Of all 336 patients, 224
      underwent LAG, while open gastrectomy (OG) performed on the other 112 patients.
      The comparison was based on the clinicopathologic characteristics, surgical
      outcome, and follow-up results. RESULTS: There are not significant differences in
      clinicopathological characteristics between the two groups (P > 0.05). The
      operation time and first ambulation time was similar in the two groups. However,
      estimated blood loss, bowel function recovery time and duration of hospital stay
      were significantly less in the LAG group. No significant difference in morbidity
      and mortality was found between the LAG group and OG group (11.1% vs. 15.3%, P =
      0.266; 0.9% vs. 1.8%, P = 0.859). The mean number of resected lymph nodes (LNS)
      between the LAG group and OG group was similar (30.6 +/- 10.1 vs. 30.3 +/- 8.6, P
      = 0.786). Furthermore, the mean number of removed LNS in each station was not
      significantly different in the distal gastrectomy and total gastrectomy (P >
      0.05). No statistical difference was seen in 1 year survival rate (91.5% vs.
      89.8% P > 0.05) and the survival curve after surgery between the LAG group and OG
      group. CONCLUSION: Laparoscopy-assisted D2 radical gastrectomy is feasible,
      effective and has comparative oncological efficacy compared with open gastrectomy
      for advanced gastric cancer without serosal invasion.

PMID- 23158877
TI  - Rapid therapeutic response to anodal tDCS of right dorsolateral prefrontal cortex
      in acute mania.

PMID- 23158878
TI  - Response to Letter to the Editor "Static splinting in burns".

PMID- 23158879
TI  - The effects of graded motor imagery and its components on chronic pain: a
      systematic review and meta-analysis.
AB  - Graded motor imagery (GMI) is becoming increasingly used in the treatment of
      chronic pain conditions. The objective of this systematic review was to
      synthesize all evidence concerning the effects of GMI and its constituent
      components on chronic pain. Systematic searches were conducted in 10 electronic
      databases. All randomized controlled trials (RCTs) of GMI, left/right judgment
      training, motor imagery, and mirror therapy used as a treatment for chronic pain
      were included. Methodological quality was assessed using the Cochrane risk of
      bias tool. Six RCTs met our inclusion criteria, and the methodological quality
      was generally low. No effect was seen for left/right judgment training, and
      conflicting results were found for motor imagery used as stand-alone techniques,
      but positive effects were observed for both mirror therapy and GMI. A meta
      analysis of GMI versus usual physiotherapy care favored GMI in reducing pain (2
      studies, n = 63; effect size, 1.06 [95% confidence interval, .41, 1.71];
      heterogeneity, I(2) = 15%). Our results suggest that GMI and mirror therapy alone
      may be effective, although this conclusion is based on limited evidence. Further
      rigorous studies are needed to investigate the effects of GMI and its components
      on a wider chronic pain population. PERSPECTIVE: This systematic review
      synthesizes the evidence for GMI and its constituent components on chronic pain.
      This review may assist clinicians in making evidence-based decisions on managing
      patients with chronic pain conditions.

PMID- 23158880
TI  - Prevention of preterm birth--why can't we do any better?

PMID- 23158881
TI  - Defining the role of sequential therapy for H pylori infection.

PMID- 23158882
TI  - Effectiveness of the ten-valent pneumococcal Haemophilus influenzae protein D
      conjugate vaccine (PHiD-CV10) against invasive pneumococcal disease: a cluster
      randomised trial.
AB  - BACKGROUND: The Finnish Invasive Pneumococcal disease (FinIP) vaccine trial was
      designed to assess the effectiveness of a pneumococcal vaccine containing ten
      serotype-specific polysaccharides conjugated to Haemophilus influenzae protein D,
      tetanus toxoid, and diphtheria toxoid as the carrier proteins (PHiD-CV10) against
      invasive pneumococcal disease. METHODS: In this cluster-randomised, double-blind
      trial, children aged younger than 19 months received PHiD-CV10 in 52 clusters or
      hepatitis vaccines as control in 26 clusters. Infants aged younger than 7 months
      at the first vaccination received either a 3+1 or a 2+1 vaccination schedule,
      children aged 7-11 months received a 2+1 schedule, and those 12-18 months of age
      received a two-dose schedule. The primary and secondary objectives were to assess
      vaccine effectiveness against culture-confirmed invasive pneumococcal disease due
      to any of the ten vaccine serotypes for the 3+1 and 2+1 schedules, respectively,
      in children who received at least one PHiD-CV10 dose before 7 months of age.
      Masked follow-up of pneumococcal disease lasted from the first vaccination (from
      February, 2009, to October, 2010) to January 31, 2012. Invasive disease data were
      retrieved from data accumulated in the national infectious diseases register.
      This trial and the nested acute otitis media trial are registered with
      ClinicalTrials.gov, numbers NCT00861380 and NCT00839254, respectively. FINDINGS:
      47,369 children were enrolled from February, 2009, to October, 2010. 30,528
      participants were assessed for the primary objective. 13 culture-confirmed
      vaccine-type cases of invasive pneumococcal disease were detected: none in the
      PHiD-CV10 3+1 group, one in the PHiD-CV10 2+1 group, and 12 in the control
      groups. The estimates for vaccine effectiveness were 100% (95% CI 83-100) for
      PHiD-CV10 3+1 and 92% (58-100) for PHiD-CV10 2+1 groups. Two cases of any culture
      confirmed invasive disease irrespective of serotype were detected in combined
      PHiD-CV10 infant cohorts compared with 14 in the corresponding control cohorts
      (vaccine effectiveness 93%, 75-99). In catch-up cohorts, seven cases of invasive
      disease were reported, all in the control group: two cases in the children
      enrolled at 7-11 months of age; and five cases in children enrolled at 12-18
      months of age (vaccine effectiveness 100%, 79-100). Non-fatal serious adverse
      events suspected to be vaccine-related were reported via routine post
      immunisation safety surveillance in 18 children. INTERPRETATION: This nationwide
      trial showed high PHiD-CV10 effectiveness against invasive pneumococcal disease
      when given in different schedules. For the first time, effectiveness of a 2+1
      schedule in infants was confirmed in a clinical trial. FUNDING: GlaxoSmithKline
      Biologicals SA and National Institute for Health and Welfare, Finland.

PMID- 23158884
TI  - More evidence for use of pneumococcal conjugate vaccines.

PMID- 23158885
TI  - An abdominal attack of hereditary angio-oedema.

PMID- 23158883
TI  - Preventing preterm births: analysis of trends and potential reductions with
      interventions in 39 countries with very high human development index.
AB  - BACKGROUND: Every year, 1.1 million babies die from prematurity, and many
      survivors are disabled. Worldwide, 15 million babies are born preterm (<37 weeks'
      gestation), with two decades of increasing rates in almost all countries with
      reliable data. The understanding of drivers and potential benefit of preventive
      interventions for preterm births is poor. We examined trends and estimate the
      potential reduction in preterm births for countries with very high human
      development index (VHHDI) if present evidence-based interventions were widely
      implemented. This analysis is to inform a rate reduction target for Born Too
      Soon. METHODS: Countries were assessed for inclusion based on availability and
      quality of preterm prevalence data (2000-10), and trend analyses with projections
      undertaken. We analysed drivers of rate increases in the USA, 1989-2004. For 39
      countries with VHHDI with more than 10,000 births, we did country-by-country
      analyses based on target population, incremental coverage increase, and
      intervention efficacy. We estimated cost savings on the basis of reported costs
      for preterm care in the USA adjusted using World Bank purchasing power parity.
      FINDINGS: From 2010, even if all countries with VHHDI achieved annual preterm
      birth rate reductions of the best performers for 1990-2010 (Estonia and Croatia),
      2000-10 (Sweden and Netherlands), or 2005-10 (Lithuania, Estonia), rates would
      experience a relative reduction of less than 5% by 2015 on average across the 39
      countries. Our analysis of preterm birth rise 1989-2004 in USA suggests half the
      change is unexplained, but important drivers include non-medically indicated
      labour induction and caesarean delivery and assisted reproductive technologies.
      For all 39 countries with VHHDI, five interventions modelling at high coverage
      predicted a 5% relative reduction of preterm birth rate from 9.59% to 9.07% of
      livebirths: smoking cessation (0.01 rate reduction), decreasing multiple embryo
      transfers during assisted reproductive technologies (0.06), cervical cerclage
      (0.15), progesterone supplementation (0.01), and reduction of non-medically
      indicated labour induction or caesarean delivery (0.29). These findings translate
      to roughly 58,000 preterm births averted and total annual economic cost savings
      of about US$3 billion. INTERPRETATION: We recommend a conservative target of a
      relative reduction in preterm birth rates of 5% by 2015. Our findings highlight
      the urgent need for research into underlying mechanisms of preterm births, and
      development of innovative interventions. Furthermore, the highest preterm birth
      rates occur in low-income settings where the causes of prematurity might differ
      and have simpler solutions such as birth spacing and treatment of infections in
      pregnancy than in high-income countries. Urgent focus on these settings is also
      crucial to reduce preterm births worldwide. FUNDING: March of Dimes, USA, Eunice
      Kennedy Shriver National Institute of Child Health and Human Development, and
      National Institutes of Health, USA.

PMID- 23158887
TI  - Quality of life in type II diabetic patients in primary health care.
AB  - INTRODUCTION: This study evaluated the quality of life of patients with type II
      diabetes in primary health care with the Turkish version of the Audit of Diabetes
      Dependent Quality of Life (ADDQoL) instrument. MATERIAL AND METHODS: A total of
      180 patients diagnosed with type II diabetes and registered at an urban primary
      health care unit in Turkey were included to this study. RESULTS: The ADDQoL
      instrument showed good internal consistency and factor structure. Diabetes had
      the largest impact on "enjoyment of food" (mean impact rating -1.65) and the
      least impact on "others fussing" (-0.44). The duration of diabetes and insulin
      therapy had a significant impact on quality of life among diabetic patients.
      CONCLUSION: Multidimensional assessments of quality of life including both
      generic and disease-specific measures are important for diabetic patients in
      primary health care. FUNDING: not relevant TRIAL REGISTRATION: not relevant.

PMID- 23158886
TI  - Sequential versus triple therapy for the first-line treatment of Helicobacter
      pylori: a multicentre, open-label, randomised trial.
AB  - BACKGROUND: Whether sequential treatment can replace triple therapy as the
      standard treatment for Helicobacter pylori infection is unknown. We compared the
      efficacy of sequential treatment for 10 days and 14 days with triple therapy for
      14 days in first-line treatment. METHODS: For this multicentre, open-label,
      randomised trial, we recruited patients (>=20 years of age) with H pylori
      infection from six centres in Taiwan. Using a computer-generated randomisation
      sequence, we randomly allocated patients (1:1:1; block sizes of six) to either
      sequential treatment (lansoprazole 30 mg and amoxicillin 1 g for the first 7
      days, followed by lansoprazole 30 mg, clarithromycin 500 mg, and metronidazole
      500 mg for another 7 days; with all drugs given twice daily) for either 10 days
      (S-10) or 14 days (S-14), of 14 days of triple therapy (T-14; lansoprazole 30 mg,
      amoxicillin 1 g, and clarithromycin 500 mg for 14 days; with all drugs given
      twice daily). Investigators were masked to treatment allocation. Our primary
      outcome was the eradication rate in first-line treatment by intention-to-treat
      (ITT) and per-protocol (PP) analyses. This trial is registered with
      ClinicalTrials.gov, number NCT01042184. FINDINGS: Between Dec 28, 2009, and Sept
      24, 2011, we enrolled 900 patients: 300 to each group. The eradication rate was
      90.7% (95% CI 87.4-94.0; 272 of 300 patients) in the S-14 group, 87.0% (83.2
      90.8; 261 of 300 patients) in the S-10 group, and 82.3% (78.0-86.6; 247 of 300
      patients) in the T-14 group. Treatment efficacy was better in the S-14 group than
      it was in the T-14 group in both the ITT analysis (number needed to treat of 12.0
      [95% CI 7.2-34.5]; p=0.003) and PP analyses (13.7 [8.3-40], p=0.003). We recorded
      no significant difference in the occurrence of adverse effects or in compliance
      between the three groups. INTERPRETATION: Our findings lend support to the use of
      sequential treatment as the standard first-line treatment for H pylori infection.
      FUNDING: National Taiwan University Hospital and National Science Council.

PMID- 23158888
TI  - Ultrasound follow-up for gallbladder polyps less than 6 mm may not be necessary.
AB  - INTRODUCTION: The management of ultrasound (US) detected gallbladder (GB) polyps
      remains a dilemma. The aim of this study was to assess the size distribution and
      the outcome of US follow-up of GB polyps. MATERIAL AND METHODS: The study was
      approved by the Danish Data Protection Agency. US reports from patients examined
      with abdominal US in our department from January 2008 to the end of December 2009
      were reviewed with a view to including all patients with GB polyps. Patients with
      GB polyps are routinely recommended a 2-year follow-up with US every six months.
      The GB polyp size was recorded at baseline and at subsequent US reports.
      Pathology reports were finally reviewed for all patients with GB polyps to check
      who underwent cholecystectomy and to register the histological diagnosis.
      RESULTS: A total of 203 patients (median age 54 years; range 19-95 years) with GB
      polyps were included; 89 (44%) men and 114 (56%) women. The mean polyp size was 5
      mm (range 2-40 mm). In 143 patients (70%) the GB polyp diameter was less than 6
      mm. The first US follow-up was performed in 120 patients (59%), and only 31 (15%)
      completed the full 2-year US follow-up programme. Polyp size was stable in 100
      patients, decreased in five patients, increased in eight and resolved in 15
      patients. A total of 13 patients (6%) underwent cholecystectomy. Of the 203
      patients, none showed neoplastic or malignant GB polyps. CONCLUSION: We recommend
      that follow-up US of patients with GB polyps < 6 mm is avoided. Alternatively,
      the intervals between US follow-up of GB polyps < 6 mm may be extended. FUNDING:
      not relevant. TRIAL REGISTRATION: not relevant.

PMID- 23158889
TI  - Risk of post-traumatic stress disorder among Danish junior medical officers
      deployed to Afghanistan is not increased.
AB  - INTRODUCTION: Since August 2006, the Danish Armed Forces have deployed junior
      medical officers (JMOs) to the Helmand Province in Afghanistan. Research has
      shown an increased incidence of post-traumatic stress disorder (PTSD) in deployed
      military personnel throughout the history of modern warfare. No investigation of
      the mental health of Danish military medical personnel has been performed. We
      wanted to investigate the extent of potentially traumatizing events experienced
      by Danish JMOs and the prevalence of PTSD among them. MATERIAL AND METHODS: We
      included all JMOs deployed for one or more tours of duty in Afghanistan from
      January 2006 to August 2010. Potential participants received a questionnaire to
      their home address including the PTSD Checklist - Civilian Version (PCL-C).
      RESULTS: A total of 72 JMOs were included in the survey. The completion rate was
      65%. We found that 98% of the respondents had experienced a potentially
      traumatizing event and that 47% had experienced feeling fear, horror or
      helplessness in the context of such an event. The prevalence of PTSD was 0%.
      CONCLUSION: Danish JMOs do not seem to have an increased risk of PTSD after
      deployment to Afghanistan. However, further research on the mental health of this
      personnel group is needed. FUNDING: This study was partly funded by The Danish
      Armed Forces Health Services. TRIAL REGISTRATION: This study was registered with
      the Danish Data Protection Agency.

PMID- 23158890
TI  - Treatment of critical illness polyneuropathy and/or myopathy - a systematic
      review.
AB  - INTRODUCTION: The objective was to search the literature with a view to providing
      a general description of critical illness myopathy/polyneuropathy (CIM/CIP),
      including its genesis and prevention. Furthermore, it was our aim to determine
      whether new treatments have occurred in the past five years. MATERIAL AND
      METHODS: PubMed, Cinahl and Swedmed+ were searched using the terms CIM, CIP and
      intensive care. The search was narrowed by adding the limits: humans, English,
      Danish, Norwegian, Swedish and, furthermore, articles had to have been published
      in the past five years as we aimed to focus on new knowledge. RESULTS: A total of
      74 articles were found. We excluded articles focusing on children and intensive
      care, tight insulin therapy in patients without CIM/CIP and articles focusing on
      Guillain-Barre syndrome, triage, bleeding, alcohol or meningitis. Of the
      remaining 36 articles, only five focused on CIM/CIP treatment. Their relevant
      original references were found and used too. CONCLUSION: CIM/CIP is the most
      commonly occurring intensive care unit (ICU)-acquired neuromuscular dysfunction,
      and it is associated with a significant increase in length of stay, delayed
      weaning from mechanical ventilation, prolonged rehabilitation and, consequently,
      more expenses. To treat/prevent this condition, it seems reasonable to ensure
      maximal functional status for survivors of an ICU-stay by applying a multimodal
      therapeutic approach that includes intensive insulin therapy, minimal sedation
      and, as suggested by new evidence, early physiotherapy and electrical muscle
      stimulation.

PMID- 23158891
TI  - Time telling devices used in Danish health care are not synchronized.
AB  - INTRODUCTION: Many patients begin their encounter with the health-care services
      in an ambulance. In some critical patients, it is pivotal that the timing of
      treatment and events is registered correctly. When patients are transferred from
      one health care provider to another, there is a risk that the time telling
      devices used are not synchronized. It has never been examined if this is a
      problem in Denmark. We performed the present study to examine if time telling
      devices used in the pre-hospital setting were synchronized with devices used in
      emergency departments. MATERIAL AND METHODS: We used an on-line atomic clock as
      reference time. The reference time was compared to watches found in the
      resuscitation rooms at emergency departments at two hospitals in Denmark.
      Furthermore, we compared the reference time to the watches on the defibrillators
      in the ambulances at two ambulance stations. RESULTS: The watches in the
      Emergency Department at Sydvestjysk Hospital Esbjerg had a median deviation of
      minus three minutes. In the Emergency Department at Hospital Lillebaelt Kolding,
      we found a median deviation of minus 30 seconds. The watches in the
      defibrillators of 11 ambulances had a median deviation of minus 45 seconds. The
      maximum deviation between two devices was 19 minutes and 5 seconds, and the
      maximum deviation between a wall-mounted clock in an emergency department and a
      defibrillator in an ambulance was five minutes and 22 seconds. CONCLUSION:
      Examining the time telling devices at two Danish emergency departments and 11
      ambulances demonstrated that they are not synchronized. FUNDING: not relevant.
      TRIAL REGISTRATION: not relevant. The study was not registered, as it is an
      observational study.

PMID- 23158892
TI  - Immediate weight-bearing after osteosynthesis of proximal tibial fractures may be
      allowed.
AB  - INTRODUCTION: Immediate weight-bearing following osteosynthesis of proximal
      tibial fractures is traditionally not allowed due to fear of articular fracture
      collapse. Anatomically shaped locking plates with sub-articular screws could
      improve stability and allow greater loading forces. The purpose of this study was
      to investigate if immediate weight-bearing can be allowed following locking plate
      osteosynthesis of proximal tibial fractures. MATERIAL AND METHODS: Locking plate
      osteosynthesis of partial articular proximal tibial fractures
      (Arbeitsgemeinschaft fur Osteosynthesefragen type 41B) operated from November
      2007 to September 2009 at Hvidovre Hospital were included retrospectively (n =
      32). Complications, reoperations and radiographic outcome at 6-8 week of follow
      up were assessed. Twenty patients were not allowed to bear weight the first 6-8
      weeks, whereas twelve were allowed immediate postoperative weight-bearing.
      RESULTS: The use of bone allograft, the number of screws inserted and the
      application of postoperative articular mobilizing brace were comparable between
      the two groups (p = 0.08). Persisting depressions of the articular surface ranged
      from 0 to 5 mm postoperatively with no difference between the groups (p = 0.36).
      At 6-8 weeks postoperatively, no changes in radiographic configuration of the
      fracture site were observed in either group. CONCLUSION: This retrospective study
      suggests that immediate weight-bearing following locking plate osteosynthesis of
      partial articular proximal tibial fractures may be allowed. Future, larger
      prospective randomised studies are needed. FUNDING: not relevant. TRIAL
      REGISTRATION: not relevant.

PMID- 23158893
TI  - Relatively high incidence of complications after loop ileostomy reversal.
AB  - INTRODUCTION: A de-functioning loop ileostomy (LI) reduces the consequences of
      anastomotic leak following low anterior resection, but its construction as well
      as its closure can be associated with complications. The aim of the present study
      was to identify risk factors for postoperative complications and particularly to
      determine if operation performed by trainees carry a higher risk of complications
      than operation performed by experienced surgeons. MATERIAL AND METHODS: This was
      a retrospective single-centre analysis of the medical records of 159 consecutive
      patients who underwent LI closure following low anterior resection for rectal
      cancer in the period from January 2002 to December 2008. RESULTS: Postoperative
      complications developed in 32 patients (20.1%). Surgical complications occurred
      in 27 patients (17%) including small bowel obstruction in five (3%), anastomotic
      leak in four (2.5%), wound infection in eight (5%) and incisional hernia in eight
      (5%). There was no postoperative mortality. Univariate analysis showed that an
      increased rate of complications was associated with female gender (p = 0.02),
      small bowel resection at closure (p = 0.009) and a long interval between
      construction and closure of the loop ileostomy (p = 0.049). CONCLUSION: Closure
      of an LI is associated with a low mortality, but a relatively high rate of
      complications. Operation performed by trainees was not associated with an
      increased complication rate. More complications were seen in patients who
      underwent small bowel resection and those who had delayed ileostomy closure.
      FUNDING: not relevant TRIAL REGISTRATION: not relevant.

PMID- 23158894
TI  - Implantable loop recorder is an effective diagnostic tool for unexplained
      syncope.
AB  - INTRODUCTION: Patients with cardiac syncope have a significantly higher mortality
      than patients with syncope of non-cardiac causes, while patients with syncope of
      unknown aetiology constitute an intermediate risk group, presumably because this
      group is mixed, which suggests that further diagnostic testing is warranted.
      MATERIAL AND METHODS: This was a retrospective single-centre study evaluating the
      diagnostic yield of an implantable loop recorder (ILR) in establishing the cause
      of recurrent, unexplained syncope. RESULTS: A total of 44 patients received ILR
      between 2007 and 2011. Follow-up data were available for 39 patients, the mean
      age was 63 years (range 23-94 years), 59% were female and the mean follow-up
      period was 349 days. The average time to first recurrence of syncope with ECG
      documentation was 244 days (range 11-699 days). The mean follow-up for the total
      population was 349 days (range 11-1,083 days) and for the group without
      recurrence 460 days (range 176-1,083 days). Diagnoses were obtained in 22
      patients (56%) of which the cause of syncope was cardiac in 64%. CONCLUSION: ILR
      was an effective tool to establish an arrhythmic cause of the recurrent,
      unexplained syncope, and useful in ruling out arrhythmia as a cause of syncope.
      New studies are needed to demonstrate whether very prolonged monitoring in case
      of absent recurrence may further improve the diagnostic yield. Additionally,
      there is much need for randomized controlled trials to investigate whether ILR
      guided therapy reduces recurrence rate and mortality. FUNDING: not relevant.
      TRIAL REGISTRATION: not relevant.

PMID- 23158895
TI  - Effects of liraglutide on neurodegeneration, blood flow and cognition in
      Alzheimer's disease - protocol for a controlled, randomized double-blinded trial.
AB  - INTRODUCTION: Type 2 diabetes (DM-2) increases the risk of developing Alzheimer's
      disease (AD), and patients with AD are more likely to develop DM-2. DM-2 and AD
      share some pathophysiological features. In AD, amyloid-beta (Abeta) is
      accumulated as extracellular plaques in the gray matter of the brain, while in DM
      2 islet amyloid polypeptide (IAPP) is accumulated in the pancreas. Premature
      cellular degeneration is seen in both diseases. Glucagon-like peptide-1 (GLP-1)
      reduces the amount of Abeta and improves cognition in animal studies. The present
      study tests the hypothesis that treatment with the long-acting GLP-1 receptor
      agonist liraglutide affects the accumulation of Abeta in patients with AD.
      MATERIAL AND METHODS: This is a randomized, controlled, double-blinded
      intervention study with AD patients treated for six months with liraglutide (n =
      20) or placebo (n = 20). The primary outcome is change in deposition of Abeta in
      the central nervous system (CNS) by Pittsburgh compound B positron emission
      tomography (PET). The secondary outcome is evaluation of cognition using a neuro
      psychological test battery, and examination of changes in glucose uptake in the
      CNS by 18F-fluoro-deoxy-glucose PET. Finally, a perfusion-weighted magnetic
      resonance imaging with contrast will be performed to evaluate blood flow.
      CONCLUSION: No registered drug affects the deposition of Abeta in the brain of AD
      patients. Our goal is to find a new therapeutic agent that alters the
      pathophysiology in AD patients by decreasing the formation of Abeta plaques and
      thereby presumably improves the cognitive function. FUNDING: The trial is
      investigator-initiated and investigator-driven and is supported by Novo Nordisk
      Scandinavia. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01469351.

PMID- 23158896
TI  - Promising early results after hand-assisted laparoscopic partial nephrectomy  in
      carefully selected patients.
AB  - INTRODUCTION: The incidence of the diagnosis of renal cell carcinoma has
      increased during the past two decades. Kidney damage occurring beyond 30 min of
      warm ischaemia is significant and mostly irreversible, even in completely normal
      renal systems. The aim of this study was to evaluate the role and safety of early
      removal of renal artery clamps and its influence on warm ischaemia time and renal
      function. MATERIAL AND METHODS: Data from 15 patients who underwent hand-assisted
      laparoscopic partial nephrectomy (HALPN) were collected retrospectively. The
      operative method was as follows. The kidney was dissected using hand-assisted
      laparoscopic technique, the gerotic fascia was dissected and a complete
      exploration of the kidney was achieved. A vascular bulldog clamp was removed from
      the renal artery immediately after the tumour resection bed had been closed with
      a running suture with Hem-o-Lok clips at either end. RESULTS: The size of tumours
      ranged between 2 cm and 7 cm. The mean warm ischaemia time was 11.2 min. The mean
      estimated glomerular filtration rate had decreased by 7.8 ml/min/1.73 m(2) metres
      (11%) six months after the operation. The estimated blood loss was less than 200
      ml. The mean operating time was 119 min and the mean postoperative hospital stay
      was 3.2 days. There was no need for postoperative blood transfusions, and neither
      delayed bleeding nor urinary leakage occurred. CONCLUSION: Early removal of renal
      artery clamps during HALPN is associated with a considerable decrease in warm
      ischaemia time and renal function preservation and pre- and postoperative
      outcomes are acceptable. FUNDING: not relevant. TRIAL REGISTRATION: not relevant.

PMID- 23158897
TI  - Data from clinical database on septic shock are valid.
AB  - INTRODUCTION: Clinical databases have become important tools in intensive care.
      Disease severity and organ dysfunction scoring systems are registered in the
      databases, including the Simplified Acute Physiology Score II (SAPS II) and the
      Sequential Organ Failure Assessment (SOFA) score. The purpose of this study was
      to evaluate the reliability and accuracy of a clinical database on intensive care
      unit (ICU) patients. MATERIAL AND METHODS: Data were extracted from the clinical
      database, Critical Information System (CIS). We included all adult patients
      admitted to one of seven Danish ICUs between 1 January 2008 and 31 December 2010
      diagnosed with septic shock. Validation of the diagnosis of septic shock and SAPS
      II and SOFA scores were obtained on every tenth patient by comparing data entries
      in CIS with the source data stored in the unit. RESULTS: A total of 1,353
      patients were identified and data on 142 patients were selected for validation.
      All but one patient (99%, 95% confidence interval (CI): 95-100) fulfilled the
      diagnostic criteria for septic shock. We found less than 10% variation in SAPS II
      in 78% (95% CI: 73-86) and less than 10% variation in SOFA scores in 80% (95% CI:
      72-85) of the cases. The average bias between the registered and corrected SAPS
      II according to the Bland-Altman plot was -1.8 (limits of agreement: -10.1 to
      6.6). Furthermore, the average bias between the registered and corrected SOFA
      score according to the Bland-Altman plot was -0.2 (limits of agreement: -2.4 to
      2.0). CONCLUSION: The accuracy of the diagnosis of septic shock was high and both
      SAPS II and SOFA scores were reliable and accurately recorded in the ICU
      database. FUNDING: not relevant. TRIAL REGISTRATION: not relevant.

PMID- 23158898
TI  - On the biology of the bony otic capsule and the pathogenesis of otosclerosis.
AB  - In human otosclerosis, focal pathological bone remodeling occurs in significant
      amounts inside the normally anti-resorptive perilabyrinthine domain of the bony
      otic capsule. Otosclerosis causes hearing loss in 0.2-0.5% of the population by
      ankylosis of the footplate. The disease cannot be predicted, avoided or medically
      reversed as the pathogenesis remains unknown. Previously genetic research has
      failed to identify a specific otosclerosis-gene and earlier theories of virus
      infections, autoimmunity or association to generalized bone diseases have been
      unable to explain why otosclerosis only occurs in the bony otic capsule while the
      rest of the skeleton remains completely normal.  Studies from the otopathological
      laboratory (RH) have revealed how the bone turnover rates increase centrifugally
      from a sub-normal 0.1% adjacent to the inner ear space towards a normal 10% per
      year at the capsular periphery. This graded restriction of bone remodeling is
      most likely caused by the anti-resorptive action of the cytokine osteoprotegerin
      (OPG), which is expressed in high levels (1000 x normal bone levels) by inner ear
      structures to inhibit perilabyrinthine osteoclast formation and function. OPG
      knockout mice develop excessive, irregular bone remodeling, stapes fixation and
      progressive hearing loss. The lacuno-canalicular porosity is the candidate
      anatomical routes for the transmission of OPG-derived signals to the surrounding
      bone. This extracellular signaling pathway depends crucially on the viability of
      individual osteocytes. When bone remodeling is low, the average age of the bone
      matrix and osteocytes increases. We detected a high fetal density of labyrinthine
      osteocytes, which may secure a life-long anatomical route for inner ear OPG
      despite accumulation of non-viable osteocytes. Moreover, 3-D reconstructions and
      vector-based stereology revealed a co-existence between non-viable osteocytes and
      otosclerosis. We suggest that bone remodeling may commence when the effect of
      anti-resorptive OPG fails locally within regions of non-viable osteocytes. A
      sustained OPG signal from surrounding osteocyte survivors might distort the
      process and account for the otosclerotic morphology.

PMID- 23158899
TI  - Postamputation pain: studies on mechanisms.
AB  - Amputation is followed by both painful and non-painful phantom phenomena in a
      large number of amputees. Non-painful phantom sensations rarely pose any clinical
      problem, but 60-80% of all amputees also experience painful sensations (i.e.
      phantom pain) located to the missing limb. The severity of phantom pain usually
      decreases with time, but severe pain persists in 5-10% of patients. Pain in the
      residual limb (i.e. stump pain) is another consequence of amputation. Both stump
      and phantom pain can be very difficult to treat. Treatment guidelines used for
      other neuropathic pain conditions are probably the best approximation, especially
      for the treatment of stump pain. The aim of the present doctoral thesis was to
      explore some of the mechanisms underlying pain after amputation. Ten studies were
      carried out (I-X).  My PhD thesis from 1998 dealt with pain before the amputation
      and showed that preamputation pain increases the risk of phantom pain after
      amputation (I). A perioperative epidural blockade, however, did not reduce the
      incidence of pain or abnormal sensory phenomena after amputation (II, III).  The
      importance of sensitization before amputation for the subsequent development of
      pain is supported by study IV, in which pressure pain thresholds obtained at the
      limb before amputation were inversely related to stump and phantom pain after 1
      week.  Afferent input from the periphery is likely to contribute to
      postamputation pain as sodium channels were upregulated in human neuromas (VI),
      although neuroma removal did not always alleviate phantom pain (V). 
      Sensitization of neurons in the spinal cord also seems to be involved in pain
      after amputation as phantom pain was reduced by ketamine, an NMDA-receptor
      antagonist. Another NMDA-receptor antagonist, memantine, and gabapentin, a drug
      working by binding to the delta2alpha-subunit of voltage-gated calcium channels,
      had no effect on phantom pain (VII-IX).  Supraspinal factors are also important
      for pain after amputation as catastrophizing was associated with phantom pain
      (X).  In conclusion, the present doctoral thesis confirmed and expanded the
      findings by others that several mechanisms are involved in the development and
      maintenance of phantom pain. A better understanding of the underlying mechanisms
      will hopefully lead to improved treatment of pain after amputation in the future.

PMID- 23158900
TI  - Spontaneous dissection of all 3 coronary arteries in a postpartum woman.

PMID- 23158901
TI  - The experience of lung cancer in Aboriginal and Torres Strait Islander peoples
      and what it means for policy, service planning and delivery.
AB  - BACKGROUND: Aboriginal and Torres Strait Islander peoples experience inferior
      outcomes following diagnosis of lung cancer. AIM: To examine the experience of
      lung cancer in this population and identify reasons for poorer outcomes and lower
      levels of treatment compared with non-Aboriginal and Torres Strait Islander
      peoples, and opportunities for early intervention. METHOD: Literature was sought
      via electronic database searches and journal hand-searching for the period from
      January 1995 to July 2010. Databases used included Indigenous HealthInfoNet,
      SCOPUS, PsycInfo, Cumulative Index to Nursing and Allied Health Literature
      (CINAHL), Medline, HealthInsite and Google Scholar. FINDINGS: Exposure to risk
      factors, cultural and spiritual values, remoteness and geographic
      characteristics, entrenched socioeconomic inequalities and racism contribute to
      reduced service access and poor outcomes. The review highlighted a complex
      interplay of individual, social, health system and environmental factors that
      impact on optimal lung cancer care and lung cancer outcomes. Considering the
      burden of lung cancer within a framework of social determinants of health is
      necessary for policy-making and service planning and delivery. CONCLUSIONS: It is
      imperative that the disproportionate burden of lung cancer in Aboriginal and
      Torres Strait Islander peoples is addressed immediately. Whilst strategic
      interventions in lung cancer prevention and care are needed, service providers
      and policy makers must acknowledge the entrenched inequality that exists and
      consider the broad range of factors at the patient, provider and system level.
      Primary care strategies and health promotion activities to reduce risk factors,
      such as smoking, must also be implemented, with Aboriginal and Torres Strait
      Islander peoples' engagement and control at the core of any strategy. This review
      has indicated that multifaceted interventions, supported by enabling policies
      that target individuals, communities and health professionals, are necessary to
      improve lung cancer outcomes and disparities.

PMID- 23158902
TI  - [Staphylococcus spp. bacteremia in patients older than 80 years].

PMID- 23158903
TI  - [Giant hydatid cyst of the liver].

PMID- 23158904
TI  - [Epidemiology of helminthiasis in a hospital in southern Madrid].

PMID- 23158905
TI  - Flavanocoumarins from Guazuma ulmifolia bark and evaluation of their affinity for
      STAT1.
AB  - From the bark of Guazuma ulmifolia, a plant used as anti-inflammatory remedy, the
      flavanocoumarin epiphyllocoumarin (1) along with epiphyllocoumarin-[4beta->8]-(-)
      epicatechin (2) and epiphyllocoumarin-[4beta->8]-(-)-epicatechin-[4beta->8]-(-)
      epicatechin (3), never reported before, have been isolated. The structures of the
      proantocyanidins 2-3 have been elucidated by extensive NMR and ESI-MS analysis.
      On the basis of the flavane nature of the isolated compounds and considering the
      strong anti-STAT1 activity reported for epigallocatechin 3-O-gallate (EGCG), the
      affinity of compounds 1-3 for STAT1 has been evaluated by Surface Plasmon
      Resonance. Compounds 1-2 showed affinity for STAT1 comparable to that exerted by
      EGCG. In order to confirm this result, molecular docking studies to evaluate the
      interactions of compounds 1-3, phyllocoumarin (4), the reference compound EGCG
      (5), and its related compound (+)-gallocatechin 3-O-gallate (6) with STAT1 have
      been carried out. Furthermore the ability of compounds 1-3 to inhibit STAT1
      activation has been evaluated using a nuclear extract obtained from the human
      monocytic leukemia cell line TPH-1. Flavanocoumarins 1-2 inhibited STAT1-DNA
      binding.

PMID- 23158907
TI  - Cardiac valve disease: an unreported feature in Ehlers Danlos syndrome
      arthrocalasia type?
AB  - Ehlers Danlos syndrome (EDS) athrocalasia type (type VII), is characterized by
      joint hypermobility, skin hyperextensibility and tissue fragility. No heart
      involvement has been reported. Two forms have been described: type VII A and VII
      B. The abnormally processed collagen alpha2(I) and the skipping of the exon 6 in
      COL1A2 gene are typically detected in EDS type VII B. We describe a seven-year
      old female, with a phenotype consistent with EDS type VII B and a diagnosis
      further confirmed by biochemical and molecular analyses. Cardiac ultrasound
      showed normal data in the first year of life. When she was 5 years old, the
      patient developed mitral valve regurgitation, and aortic and tricuspidal
      insufficiency at 7 years of age. To our knowledge, this is the first report of
      cardiac valvular involvement in EDS VII B. This feature probably has been
      underreported for the limited follow-up of the patients. Echocardiography might
      be warranted in the clinical assessment of EDS VII patients.

PMID- 23158908
TI  - Biomarkers of small intestinal mucosal damage induced by chemotherapy: an
      emerging role for the 13C sucrose breath test.
AB  - Gastrointestinal mucosal toxicity is extremely common following cytotoxic
      therapies. The alimentary mucosa is particularly susceptible to injury and
      dysfunction, leading to many debilitating complications. Despite much research,
      there is currently no single noninvasive biomarker to detect gut injury. Several
      biomarkers have been investigated in the context of gastrointestinal diseases,
      which may prove useful in the oncology arena. Identification of a biomarker that
      is easy to obtain and measure and that accurately identifies mucosal damage would
      allow for improved patient diagnosis of toxicities and for personalized treatment
      regimens. In this review, we highlight the effectiveness of urine and breath
      tests as potential clinically effective biomarkers, with significant focus placed
      on the emerging role of the carbon-13 sucrose breath test (13C SBT). The 13C SBT
      provides a simple, noninvasive, and integrated measure of gut function. The 13C
      SBT also has the potential to monitor gut function in the setting of cytotoxic
      therapy-induced mucositis, or in the assessment of the efficacy of antimucositis
      agents.

PMID- 23158906
TI  - Anti-HBV efficacy of combined siRNAs targeting viral gene and heat shock cognate
      70.
AB  - BACKGROUND: Hepatitis B virus (HBV) infection is a major health concern with more
      than two billion individuals currently infected worldwide. Because of the limited
      effectiveness of existing vaccines and drugs, development of novel antiviral
      strategies is urgently needed. Heat stress cognate 70 (Hsc70) is an ATP-binding
      protein of the heat stress protein 70 family. Hsc70 has been found to be required
      for HBV DNA replication. Here we report, for the first time, that combined siRNAs
      targeting viral gene and siHsc70 are highly effective in suppressing ongoing HBV
      expression and replication. METHODS: We constructed two plasmids (S1 and S2)
      expressing short hairpin RNAs (shRNAs) targeting surface open reading frame of
      HBV(HBVS) and one plasmid expressing shRNA targeting Hsc70 (siHsc70), and we used
      the EGFP-specific siRNA plasmid (siEGFP) as we had previously described. First,
      we evaluated the gene-silencing efficacy of both shRNAs using an enhanced green
      fluorescent protein (EGFP) reporter system and flow cytometry in HEK293 and T98G
      cells. Then, the antiviral potencies of HBV-specific siRNA (siHBV) in combination
      with siHsc70 in HepG2.2.15 cells were investigated. Moreover, type I IFN and TNF
      alpha induction were measured by quantitative real-time PCR and ELISA. RESULTS:
      Cotransfection of either S1 or S2 with an EGFP plasmid produced an 80%-90%
      reduction in EGFP signal relative to the control. This combinational RNAi
      effectively and specifically inhibited HBV protein, mRNA and HBV DNA, resulting
      in up to a 3.36 log10 reduction in HBV load in the HepG2.2.15 cell culture
      supernatants. The combined siRNAs were more potent than siHBV or siHsc70 used
      separately, and this approach can enhance potency in suppressing ongoing viral
      gene expression and replication in HepG2.2.15 cells while forestalling escape by
      mutant HBV. The antiviral synergy of siHBV used in combination with siHsc70
      produced no cytotoxicity and induced no production of IFN-alpha, IFN-beta and TNF
      alpha in transfected cells. CONCLUSIONS: Our combinational RNAi was sequence
      specific, effective against wild-type and mutant drug-resistant HBV strains,
      without triggering interferon response or producing any side effects. These
      findings indicate that combinational RNAi has tremendous promise for developing
      innovative therapy against viral infection.

PMID- 23158909
TI  - The 4th Pan American Conference of WADEM.

PMID- 23158910
TI  - [Exploring the cardiac rehabilitation/secondary prevention model for rejoining
      the fragmented medical services chain].

PMID- 23158911
TI  - [Emphasizing on chronic disease rehabilitation for the comprehensive improvement
      of life quality].

PMID- 23158912
TI  - [Analysis of the clinical data of patients with acute coronary syndrome
      complicated by hemorrhage during hospitalization].
AB  - OBJECTIVE: To investigate the clinical characteristics of patients with acute
      coronary syndrome suffering hemorrhage during hospitalization. METHODS: The
      clinical symptoms, diagnostic and therapeutic characteristics and in-hospital
      outcome of 3807 inpatients who were recruited into SINO-GRACE study in China due
      to acute coronary syndrome from March, 2001 to December, 2007 were collected.
      Statistical methods were adopted to compare the differences in clinical data
      between hemorrhage group and non-hemorrhage group. RESULTS: Hemorrhage had
      happened in 57 out of 3807 inpatients with the incidence of 1.50%. Five patients,
      which accounted for 9.6% of the overall hemorrhage cases, were fatal hemorrhage.
      Nine patients were intracranial hemorrhage with the incidence of 0.24%. There
      were 155 deaths among the 3807 patients, with an overall mortality rate of 4.1%.
      The mortality of hemorrhage accounted for 3.2% in overall mortality. Patients
      with one of the following factors were more apt to hemorrhage: > 70 years old,
      previous hemorrhage history, renal failure history, heart failure history and
      clopidogrel and glycoprotein (GP) IIb/IIIa receptor antagonist administration for
      coronary artery bypass grafting. Patients who developed hemorrhage might need
      prolonged hospitalization and were liable to develop heart-related adverse
      events, including re-infarction and sustained ventricular
      tachycardia/fibrillation after they were admitted in hospital over 24 hours.
      CONCLUSION: Patients with acute coronary syndrome who underwent coronary artery
      bypass grafting, with advanced age, previous hemorrhage history, renal failure
      history, heart failure history or treated with clopidogrel and GP IIb/IIIa
      receptor antagonist are more vulnerable to hemorrhage.

PMID- 23158913
TI  - [The prevalence and distributing feature of atrial fibrillation in Xinjiang Uygur
      Autonomous Region Kazaks adult population].
AB  - OBJECTIVE: To investigate the prevalence and distributing feature of atrial
      fibrillation (AF) in Xinjiang Kazaks adult population. METHODS: Four-stage
      selected random samples aged 30-89 years from Tacheng, Yili and Aletai were
      analyzed. An epidemical study of AF was performed including inquiring medical
      history, recording electrocardiogram and auscultation. RESULTS: A total of 22 514
      adults were surveyed. The prevalence of AF in Xinjiang Kazaks adult population
      was 0.37%, which was increasing with aging. The prevalence was higher in men than
      in women (0.5% vs 0.2%, P < 0.01). In AF patients, 23 was valvular AF. Ischemic
      stroke was the most frequent type and the stroke rate in the patients with AF was
      significantly higher than that without AF (6.0% vs 1.2%, P < 0.01). CONCLUSIONS:
      The prevalence of AF in Xinjiang Kazaks adult population is lower than the
      reported national prevalence but patients with AF in this population would not
      like to take the necessary medicine. Therefore, the control of AF need to be
      reinforced.

PMID- 23158914
TI  - [The impact of serum total bilirubin level on long-term prognosis in patients
      with chronic heart failure].
AB  - OBJECTIVE: To analyze the relationship between serum total bilirubin coincident
      with congestive heart failure (CHF) exacerbation and subsequent long-term
      mortality in patients with CHF. METHODS: The study population consisted of 140
      consecutive patients admitted for CHF exacerbation with left ventricular ejection
      fraction <= 45%. They were divided into 2 groups according to whether death
      attacked or not in the following 28.5 months. Binary logistic regression analysis
      was used to investigate independent predictors of death from clinical parameters
      on admission or within 24 hours. RESULTS: Serum TBil and B-type natriuretic
      peptide (BNP) levels on admission were independent predictors of subsequent death
      after hospital discharge. According to increasing textiles of TBil stratified by
      the level of 12.8 and 18.2 mmol/L, the patients were divided into 3 groups: lower
      level group (TBil <= 12.8 mmol/L), moderate-level group(TBil > 12.8 ~ 18.2
      mmol/L) and higher-level group (TBil > 18.2 mmol/L), with the death rates after
      28.5 months of 12.2%, 17.9% and 38.9%, respectively(P = 0.002). Meanwhile, the
      pulse pressure decreased to (55.5 +/- 17.3) mm Hg (1 mm Hg = 0.133 kPa), (48.9 +/
      13.1) mm Hg and (46.1 +/- 13.7) mm Hg, respectively (P = 0.008). TBil on
      admission had significant correlation with echocardiography-measured left
      ventricular endo-diastolic diameter (r = 0.34, P = 0.000) and right ventricular
      diastolic diameter (r = 0.23, P = 0.011). CONCLUSIONS: Increased TBil coincident
      with cardiac decompensation predicts a worse long-term death of CHF, presumably
      through the potential liability to both decompensated RV function and lower
      cardiac output syndrome occurred simultaneously when HF deteriorates.

PMID- 23158915
TI  - [The phenotypes of a hypercholesterolemia family with low density lipoprotein
      receptor exon 13 A606T mutation].
AB  - OBJECTIVE: To investigate the clinical phenotypes of familial
      hypercholesterolemia (FH) caused by exon 13 A606T mutation in low density
      lipoprotein receptor. METHODS: Clinical data of the suffered family were
      collected and analyzed, as well as measurement of perivascular intima-medial
      thickness and follow-mediated-dilation function by ultrasonography. RESULTS:
      There were totally 11 sufferers including 4 males and 9 females, aged 8-90 years,
      with 2 homozygotes and 9 heterozygotes. Among them, one homozygote showed angina
      pectoris and hematuria, both homozygotes had skin xanthomata. TC, TG, LDL-C and
      HDL-C were (7.39 +/- 1.30) mmol/L, (0.93 +/- 0.36) mmol/L, (11.76 +/- 1.10)
      mmol/L and (1.22 +/- 0.17) mmol/L, respectively. The left/right sided intima
      medial thickness of the common, internal, external and bulb carotid artery were
      (1.15 +/- 0.45) mm/(1.30 +/- 0.60) mm, (0.82 +/- 0.30) mm/(1.00 +/- 0.66) mm,
      (0.77 +/- 0.28) mm/(0.78 +/- 0.30) mm and (1.40 +/- 0.59) mm/(1.46 +/- 0.71) mm
      respectively. The brachial artery flow mediated dilation rate was (4.85 +/-
      4.80)%. Echocardiography revealed 2 patients with cardiac valvular disease and 3
      with atrium septum aneurysm. CONCLUSION: FH patients show a variety of phenotypes
      including extraordinary hypercholesterolemia, subcutaneous xanthomata and
      premature coronary heart disease.

PMID- 23158916
TI  - [The relationship between waist to stature ratio and hypertension, diabetes, and
      dyslipidemia in Qingdao].
AB  - OBJECTIVE: To evaluate the relationship between waist to stature ratio (WSR) and
      hypertension, diabetes, dyslipidemia in Qingdao. METHODS: Data were collected
      from a 2001 - 2007 Qingdao area diabetes survey, population-based cross-sectional
      study, and 30 712 Chinese adults aged>18 years old were enrolled. Correlation
      analysis of BMI, WSR, hip circumference, waist circumference, waist to hip ratio
      (WHR) with blood glucose, blood pressure, blood lipid were conducted. ROC curve
      analysis in diabetes, hypertension, dyslipidemia and multivariate logistic
      regression analysis were also conducted. RESULTS: Anthropometric indicators were
      related with hypertension, diabetes and dyslipidemia in both men and women.
      Comparing with other anthropometric indicators, WSR was found to have the largest
      area under the ROC curve and the best cut-off point of WSR was 0.52. Multivariate
      logistic regression analysis showed that, after controlling age, disease history,
      physical activity, sex, the diabetes hypertension and dyslipidemia risk OR of WSR
      >= 0.52 were largest. CONCLUSIONS: Anthropometric indicators intimately related
      with cardiovascular risk factors in Qingdao region, and may predict and evaluate
      the risk of cardiovascular disease. WSR may be the best index for predicting
      cardiovascular risk factors in Qingdao area. The optimal WSR cut off point for
      identifying cardiovascular risk factors clustering is 0.52.

PMID- 23158917
TI  - [The influence of carotid artery stenosis on neurological outcomes in patients
      undergoing off-pump coronary artery bypass grafting].
AB  - OBJECTIVE: To investigate the influence of carotid artery stenosis on the
      incidence of neurological complication in patients undergoing off-pump coronary
      artery bypass grafting. METHODS: We prospectively analyzed 176 consecutive
      patients >= 60 years old undergoing selective off-pump coronary artery bypass
      grafting (from June 2010 to July 2011). Carotid duplex ultrasound screening was
      used to determine the presence and severity of carotid artery before surgery.
      Neurological complications 7 days after surgery were compared between the
      patients with (>= 75%) and without severe carotid artery stenosis (< 70%).
      Multivariate analysis was used to determine the predictor of severe carotid
      artery disease. RESULTS: Sixteen patients (9.1%) were found to have severe
      carotid artery stenosis before surgery. Thirty-seven patients (20.8%) had single
      or multiple neurological complications: 1 (0.6%) had stroke; 12 (6.7%) had
      hypoxic-metabolic encephalopathy; 21 (11.8%) had cognitive dysfunction; 3 (1.7%)
      had depression. When compared with the counterparts, patients with severe carotid
      artery stenosis had a higher rate of neurological complications (43.8% vs 18.8%;
      P = 0.044). In multivariate analysis, significant predictive factor for severe
      carotid artery stenosis was prior stroke (OR: 4.04; 95%CI 1.22 - 13.37).
      CONCLUSION: Severe carotid artery stenosis alone is a risk factor for
      neurological complication after off-pump coronary artery bypass grafting and
      prior stroke is a predictor for sever carotid artery disease.

PMID- 23158918
TI  - [The value of serum intestinal fatty acid binding protein measurement in
      discriminating intestinal ischemia in patients with acute abdomen].
AB  - OBJECTIVE: To assess the differential diagnostic value of serum intestinal fatty
      acid binding protein (I-FABP) in distinguishing intestinal ischemia patients from
      acute abdomen patients. METHODS: A total of 151 patients with acute abdomen and
      17 healthy controls from the PLA General Hospital were enrolled from November,
      2009 to August, 2011. Serum I-FABP levels were measured by ELISA. According to
      the ROC curve, the cut-off value, sensitivity, specificity, positive likelihood
      ratio (PLR), negative likelihood ratio (NLR), positive predictive value (PPV) and
      negative predictive value (NPV) were calculated. RESULTS: Of the 151 acute
      abdomen patients, there were 24 intestinal ischemia patients and 127 without
      intestinal ischemia. Serum I-FABP level in intestinal ischemia group [(109.67 +/-
      48.82) ug/L] was significantly higher than those in patients without intestinal
      ischemia [(36.78 +/- 11.25) ug/L] and healthy controls[(8.33 +/- 6.25) ug/L](all
      P values < 0.01). The serum I-FABP cut-off value for the diagnosis of intestinal
      ischemia was 87.52 ug/L. Serum I-FABP was efficient in terms of sensitivity
      (0.762), NPV(0.963), PLR(3.05) and NLR (0.24) in the diagnosis of intestinal
      ischemia. CONCLUSION: I-FABP is potentially useful for discriminating intestinal
      ischemia from acute abdomen.

PMID- 23158919
TI  - [Toxic megacolon complicated by ulcerative colitis in six patients: a case report
      and literature review].
AB  - OBJECTIVE: To summarize the clinical features of ulcerative colitis (UC)
      complicated by toxic megacolon for early diagnosis and proper treatment. METHODS:
      Six cases of toxic megacolon in the patients suffered from UC in Peking Union
      Medical College Hospital from 1983 to 2010 were analyzed, and related literature
      was searched and reviewed. RESULTS: The incidence of the toxic megacolon in the
      patients with UC in our center was 0.7%(6/824), which was lower than those
      reported in the literature. There were always risk factors triggering the
      disease. The prognosis of the patients was poor, even after medical care and
      surgery intervention. Evaluation of the patients and making right timing to
      perform the surgery would improve the prognosis of the patients in foreign
      literature. CONCLUSION: It's crucial to make early diagnosis of the toxic
      megacolon in the patients suffered from UC. The right choice and timing to
      perform urgent surgery or selective surgery may improve their prognosis.

PMID- 23158920
TI  - [The clinical and muscular pathological study of dermatomyositis with
      perifascicular atrophy changes].
AB  - OBJECTIVE: To investigate the clinical and pathological characteristics of
      dermatomyositis with muscular perifascicular atrophy (PFA). METHODS: A series of
      104 consecutive patients clinically and pathologically diagnosed as
      dermatomyositis by muscle biopsy in our laboratory from December, 2003 to August,
      2011, were enrolled in this study. Muscle biopsy of all the enrolled patients had
      shown PFA of muscle fibers. RESULTS: Among the 104 patients, 34 were males and 70
      were females with a mean age of 45 years old. Among them, 8 cases had normal
      electromyogram; 42 had normal serum creatine kinase level; 11 were diagnosed as
      carcinoma; 75 were found to be combined with interstitial lung disease (ILD).
      Based on morphologic changes of muscle biopsy, they were divided into pure PFA
      group with 54 cases and PFA plus focal damage group with 50 cases. Compared with
      the pure PFA group, there was prominent mononuclear cell infiltration into
      perimysial intermediate sized vessels and membrane attack complement (MAC)
      deposition in the intramuscular capillaries in the PFA plus group. Skin biopsy
      had been taken in 12 cases together with muscle biopsy and had shown the "border
      effect" of both PFA and interface dermatitis in muscle and skin. CONCLUSIONS: Our
      study suggests that chronic immune vascular damage and insufficiency in
      dermatomyositis may cause ischemia and focal myofiber damage in "watershed"
      regions. The incidence of ILD in our dermatomyositis patients with PFA is high.

PMID- 23158921
TI  - [Relationship between body mass index and all-cause mortality in hemodialysis
      patients: a meta-analysis].
AB  - OBJECTIVE: To explore the relationship between the different body mass index
      (BMI) ranges and all cause mortality in hemodialysis (HD) patients. METHODS:
      Eligible studies assessing the effects of BMI ranges on all-cause mortality
      (published from 1966 to 2012) were searched, using "hemodialysis/haemodialysis"
      and "obese/body mass index/overweight" and "mortality/survival/reverse
      epidemiology/obesity paradox" in PubMed, Embase, ScienceDirect, Wilcy, Scopus and
      Ovid. Inclusion criteria were that trials reported mortality in HD patients
      according to the traditional WHO/NIH BMI classification, and BMI levels were
      acceptable within 2 kg/m(2). The quality of the trials was evaluated using the
      assessing risk of bias in studies included in Cochrane reviews. The mortality
      rate in HD patients was the primary endpoint of the study. RESULTS: With no
      significant heterogeneity (I(2) = 0%, P = 0.45), a fixed-effects model was used
      for analysis. Four studies with a total of 81 423 patients met final inclusion
      criteria. Compared to individuals with non-elevated BMI levels, the elevated
      group (BMI >= 25 kg/m(2)) was associated with lower all-cause mortality (OR 0.67,
      95%CI 0.65 - 0.68). In a risk-adjusted sensitivity analysis, elevated BMI levels
      remained protective against mortality (adjusted HR 0.94, 95%CI 0.92 - 0.96).
      CONCLUSIONS: High BMI levels are associated with lower all-cause mortality rate
      in HD patients. More stable hemodynamic status, cytokine and neurohormonal
      alternations, and nutritional status maybe contribute to the protective effects
      of BMI on the mortality of HD patients. There is a need for more prospective
      studies to elucidate underlying mechanisms.

PMID- 23158922
TI  - [Cellular HIV DNA quantitative testing and its significance in Chinese AIDS
      patients during 48 weeks' highly-active antiretroviral treatment].
AB  - OBJECTIVE: To observe the dynamic changes of peripheral blood T lymphocytes and
      monocytes, which serve as HIV-1 viral reservoirs, in Chinese HIV-infected
      patients receiving highly-active antiretroviral treatment (HAART) for 48 weeks
      and its clinical significance. METHODS: A total of 35 chronic HIV-1 infected
      adults initial received HAART. The peripheral blood T lymphocyte subsets counts
      were determined by flux cytometry at week 0, 24 and 48. Magnetic activated cell
      sorting was used to extract cellular DNA from monocytes and T lymphocytes
      purified from peripheral blood mononuclear cells. Real-time fluorescent
      quantitative PCR was used to detect the serum HIV RNA and HIV DNA of monocytes
      and T lymphocytes. SPSS 18.0 software was used to analyze the collected data.
      RESULTS: At week 0, 24, and 48 after initiation of HAART, HIV RNA levels of
      peripheral blood were (4.12 +/- 1.41), <= 1.69, and <= 1.69 lg copies/ml,
      respectively; CD(4)(+) T cells were (196 +/- 101), (321.90 +/- 112) and (392 +/-
      127) cells/ul, respectively; HIV DNA level in T lymphocytes were (4.03 +/- 0.53),
      (2.74 +/- 1.16) and (2.45 +/- 0.41) lg copies/10(6) cells respectively; while in
      monocytes, HIV DNA levels were (2.51 +/- 0.68), (2.16 +/- 0.34)and (2.03 +/-
      0.25)lg copies/10(6) cells. Statistical analysis revealed that HIV RNA level was
      negatively correlated with the CD(4)(+) T cell count through the whole trail,
      while positively correlated with the HIV DNA level in blood T lymphocytes and
      monocytes. HIV DNA level in T lymphocytes decreased more slowly than HIV DNA in
      monocytes. Moreover, peripheral blood CD(4)(+) T cell count was negatively
      associated with the HIV DNA capacity from T lymphocytes. CONCLUSIONS: Both T
      lymphocyte and monocyte may serve as viral reservoirs, and T lymphocyte might
      play a more important role as HIV reservoirs. The blood HIV RNA is correlated
      positively with the cellular HIV DNA, whereas, CD(4)(+) T cell count is
      correlated negatively with HIV DNA from lymphocytes, which suggests that HIV DNA
      levels in T lymphocyte might be one of indicators of AIDS progress during HAART.

PMID- 23158923
TI  - [Factors related to endoscopic third ventriculostomy prognosis in the paediatric
      population].
AB  - Endoscopic third ventriculostomy (ETV) for paediatric patients has different
      success rates between the published series, making its recommendation
      controversial. Different definitions of ETV success, hydrocephalus aetiology or
      patient age at diagnosis may influence the outcome of the ETV procedure. The aim
      of this work was to analyse our clinical series and to examine the influence of
      different factors on ETV outcome. This was a retrospective study of 45 patients
      who had undergone ETV at our Paediatric Hospital between 2003 and 2009.
      Successful outcome was defined as a combination of features including clinical
      improvement or stability, with at least 1 positive radiological parameter. The
      influence of age, hydrocephalus aetiology, existence or not of previous shunt and
      the type of endoscopic procedure were analysed in relation to ETV outcome. Up to
      29% of patients were younger than 1 year. The most frequent causes of
      hydrocephalus were: brain tumour, aqueductal stenosis and myelomeningocele. The
      overall success rate was 69%, with a mean follow-up period of 26 months and mean
      ETV survival of 14 months. We obtained statistically significant differences in
      ETV success between patients aged over and under 6 moths. Our ETV success rate
      can be considered safe and effective for the treatment of paediatric
      hydrocephalus. To our knowledge, ETV is most effective in patients aged 6 months
      and over.

PMID- 23158924
TI  - [Chronic subdural hematoma in young patients].
AB  - OBJECTIVE: The objective of this study was to analyse demographic, clinical and
      radiological findings and surgical results in a series of chronic subdural
      haematomas (CSDH) in young adult patients. PATIENTS AND METHODS: This
      retrospective study included 42 patients under 40 years of age who were diagnosed
      and surgically treated for a CSDH during a 30-year period (1982-2011). RESULTS:
      Of the 42 cases analysed, 32 were males and 10 were females, and the mean age at
      diagnosis was 29.3+/-8.9 years (range: 4 to 39 years). The mean interval from
      trauma to appearance of clinical symptoms was 33.4+/-9.7 days (range: 19 to 95
      days). The main symptoms were headache (59.5%) and seizures (21.4%), and the most
      frequent predisposing factors were ventriculoperitoneal shunting in 5 (11.9%)
      patients and haematological disorders in another 5 (11.9%) cases. CSDH was right
      sided in 21 cases (50%), left-sided in 19 cases (45.3%) and bilateral in the
      remaining 2 patients (4.7%). Postoperative complications occurred in 2 patients
      (1 recurrence and 1 acute subdural haematoma). CONCLUSIONS: CSDH is a rare
      pathology during the first decades of life. It mainly affects males and headache
      is usually the first symptom. Prognosis is good in young patients, since
      postoperative complications and recurrences are less frequent at this age than in
      older populations.

PMID- 23158925
TI  - [Olfactory ensheathing cell tumour: case report and literature review].
AB  - Olfactory ensheathing cells are glial cells located in the olfactory bulb and
      nerve. Microscopically, both olfactory ensheathing cells and Schwann cells have
      similar morphological and immunohistochemical features. However, olfactory
      ensheathing cells are negative for Leu-7(CD-57), whereas Schwann cells are
      positive. We present the case of a 49 year-old male with a history of visual
      impairment and hyposmia. Radiological CT and MRI studies showed a subfrontal
      cystic extra-axial mass, which eroded the right cribriform plate, with
      heterogeneous contrast enhancement. Total excision of the tumour was performed by
      bifrontal craniotomy. Histological examination initially suggested a schwannoma,
      with immunohistochemical staining being positive for S-100 protein and negative
      for epithelial membrane antigen (EMA). However, the tumour was negative for Leu
      7. Accordingly, the final diagnosis was olfactory ensheathing cell tumour.
      Herein, we describe the sixth case of intracranial olfactory ensheathing cell
      tumour and stress the important role of immunohistochemical techniques in
      obtaining a definitive diagnosis.

PMID- 23158926
TI  - Improvement of the surgical curability of locally confined prostate cancer
      including non-organ-confined high-risk disease through retropubic radical
      prostatectomy with intentional wide resection.
AB  - BACKGROUND: Retropubic radical prostatectomy with intentional wide resection (RRP
      WR), which enables clear location of the prostate apex and the performance of
      posterolateral wider resection to remove extraprostatic extension, was introduced
      to our institutions. The aim of this study is to assess the feasibility and the
      efficacy of RRP-WR as a surgical intervention for locally confined prostate
      cancer. METHODS: A total of 90 Japanese patients with pathologically proven and
      clinically locally confined hormone-naive prostate cancer were treated through
      RRP-WR, and the surgical morbidity was assessed. The patients were observed
      without immediate treatment until biochemical recurrence (BCR). RESULTS: The
      surgical morbidities were comparable to conventional procedures. No positive
      surgical margin (pSM) was pathologically identified in pT2 cases from
      prostatectomy specimens. It was identified in only 14.3% of pT3a cases, 36.4% of
      pT3b cases and 100% of pT4 cases. No apical pSM was found except for one of the
      pT4 cases in the levator ani muscle. PSA was at an undetectable level in 80.0% of
      all cases, 90.0% of pT2 cases, and 67.5% of pT3 and pT4 cases after surgery. The
      BCR-free survival rate in all cases was 82.4% and that of high-risk cases without
      pSM was 76.9% at a median follow-up of 19.3 months (3.3 to 59.2). CONCLUSIONS:
      RRP-WR is feasible and effective in removing organ-confined prostate cancer as
      well as extraprostatic extension without pSM. Thus, it is worthwhile to evaluate
      if this procedure improves the clinical outcome of locally confined prostate
      cancer including high-risk conditions treated by surgical intervention.

PMID- 23158927
TI  - Diallyl trisufide (DATS) suppresses high glucose-induced cardiomyocyte apoptosis
      by inhibiting JNK/NFkappaB signaling via attenuating ROS generation.
AB  - BACKGROUND: Hyperglycemia is an important risk factor for cardiovascular diseases
      no matter if it resulted from type I or type II diabetes mellitus. High glucose
      induced generation of reactive oxygen species (ROS) can lead to diabetic
      cardiomyopathy. In our previous study, we showed that NADPH oxidase-related ROS
      induced apoptosis is mediated via the JNK-dependent activation of NF-kappaB in
      cardiomyocytes exposed to high glucose (HG). OBJECTIVE: In this study, we
      investigated the mechanisms governing the anti-apoptotic effect of diallyl
      trisulfide (DATS) on HG-exposed cardiac cells both in vitro and in vivo. METHODS:
      H9c2 cells were incubated with media containing 5.5 or 33 mM of glucose for 36 h
      in the presence or absence of DATS. RESULTS: We found that DATS treatment led to
      a dose-dependent decrease in ROS levels as well as protein levels of p22phox,
      gp91phox, phosphorylated JNK, and phosphorylated c-Jun. In addition, DATS
      inhibited the HG-induced activation of caspase 3 as well as the nuclear
      translocation of NF-kappaB. Similar results were observed in HG-exposed neonatal
      primary cardiomyocytes and streptozotocin-treated diabetic rats.
      Echocardiographic data showed that DATS administration led to a marked increase
      in fractional shortening and cardiac output. CONCLUSION: DATS appears to suppress
      high glucose-induced cardiomyocyte apoptosis by inhibiting NADPH oxidase-related
      ROS and its downstream JNK/NF-kappaB signaling, and may possess the potential on
      the therapy of diabetic cardiomyopathy.

PMID- 23158928
TI  - CXCR6 deficiency ameliorated myocardial ischemia/reperfusion injury by inhibiting
      infiltration of monocytes and IFN-gamma-dependent autophagy.
AB  - BACKGROUND: Emerging evidence shows that the chemokine CXCL16 plays an important
      role in the pathogenesis of myocardial remodeling and development of heart
      failure following ischemia/reperfusion (I/R) injury. CXCR6, the receptor for
      CXCL16, is also critically involved. However, the underlying mechanism remained
      uncertain, and the aim of this research was to investigate this mechanism in
      CXCR6 knockout (KO) mice. METHODS AND RESULTS: CXCR6 KO mice and wild type (WT)
      mice had no overt phenotype at baseline in the absence of injury, but difference
      was shown in response to I/R induction. Compared with WT mice, CXCR6 KO mice
      exhibited a lower infarction size (31.86 +/- 1.808% vs. 43.09 +/- 1.519%), and
      better cardiac function (measured by LVEF, LVFS, +dp/dt, LVEDP, and LVSP)
      following I/R. Moreover, cardiac levels of IFN-gamma and IFN-gamma-dependent
      autophagy were found to be significantly attenuated in CXCR6 KO mice. Further
      data showed that cardiac-enhanced IFN-gamma secretion was not induced by
      cardiomyocytes, but by infiltrated monocytes in the myocardium in response to I/R
      injury. In vivo injection of IFN-gamma and in vitro co-cultured cardiomyocytes
      with CD11b+ monocytes confirmed IFN-gamma activated autophagic response, and
      induced cardiac dysfunction in a paracrine manner. CONCLUSIONS: The study
      suggested that since disruption of the CXCL16/CXCR6 signaling cascade had a
      cardio-protective effect against I/R injury, the underlying mechanism might be
      that I/R triggered the infiltration of monocytes into the myocardium, and induced
      cardiac autophagy through CXCL16/CXCR6-dependent paracrine secretion of IFN
      gamma.

PMID- 23158929
TI  - Metric analysis of loading magnitudes at articular and non-articular weight
      bearing surfaces in human calcaneus.
AB  - The calcaneus is axially loaded at its articular interface with the talus. A
      large bulk of this load is transmitted to the ground across the non-articular
      tubercles at the plantar surface of the bone. A small part of the incumbent load
      sustained by the calcaneus is directed towards the forefoot at the calcaneo
      cuboid junction. This study investigates the proportion of load distributed
      across the articular and non-articular surfaces of the calcaneus. The present
      study demonstrates strong and significant correlation between some of the load
      bearing variables and suggests the need for further investigations to understand
      the effect of angular aspects of axial loading on the calcaneus. Accounting for
      the relative distribution of weight across the articular and non-articular areas
      may enable us to appreciate the internal trabecular structure of the calcaneus in
      light of its clinical importance.

PMID- 23158930
TI  - Nonlinear closed loop optimal control: a modified state-dependent Riccati
      equation.
AB  - The state-dependent Riccati equation (SDRE), as a controller, has been introduced
      and implemented since the 90s. In this article, the other aspects of this
      controller are declared which shows the capability of this technique. First, a
      general case which has control nonlinearities and time varying weighting matrix Q
      is solved with three approaches: exact solution (ES), online control update (OCU)
      and power series approximation (PSA). The proposed PSA in this paper is able to
      deal with time varying or state-dependent Q in nonlinear systems. As a result of
      having the solution of nonlinear systems with complex Q containing constraints,
      using OCU and proposed PSA, a method is introduced to prevent the collision of an
      end-effector of a robot and an obstacle which shows the adaptability of the SDRE
      controller. Two examples to support the idea are presented and conferred.
      Supplementing constraints to the SDRE via matrix Q, this approach is named a
      modified SDRE.

PMID- 23158931
TI  - Adrenal dysfunction in polycystic ovary syndrome: has it been lost to follow-up?

PMID- 23158932
TI  - Use of metaphase I oocytes matured in vitro is associated with embryo
      multinucleation.
AB  - OBJECTIVE: To evaluate the impact of oocyte maturational stage at retrieval on
      embryo multinucleation. DESIGN: Retrospective study. SETTING: Private institution
      for assisted reproduction. PATIENT(S): A total of 412 patients undergoing 500
      intracytoplasmic sperm injection (ICSI) cycles between August 2006 and September
      2010. INTERVENTION(S): Routine ICSI laboratory procedures. MAIN OUTCOME
      MEASURE(S): Normal and abnormal fertilization; embryo development; arrest at
      pronuclear stage; failure to undergo first mitotic division; presence of embryo
      multinucleation; embryo quality; pregnancy, implantation, and miscarriage rates.
      RESULT(S): A significantly lower percentage of multinucleation was found in
      embryos originating from metaphase II (MII) oocytes when compared with MI-II- and
      MI-derived oocytes. Significantly fewer multinucleated cells per embryo were
      observed in MII-derived oocytes. Clinical pregnancy and implantation rates were
      significantly higher when only embryos derived from MII oocytes were transferred.
      CONCLUSION(S): Embryo multinucleation rate increases when in vitro-matured (2-5
      hours incubation) MI (MI-II) oocytes are used instead of in vivo-matured oocytes
      in ICSI. Furthermore, all other ICSI outcome parameters are also compromised. The
      use of donated gametes does not modify these results.

PMID- 23158933
TI  - Psoriatic patients have an increased risk of polycystic ovary syndrome: results
      of a cross-sectional analysis.
AB  - OBJECTIVE: To define the prevalence and the features of polycystic ovary syndrome
      (PCOS) in patients with psoriasis. To our knowledge, the association between PCOS
      and psoriasis has not been explored in previous studies. Psoriasis is linked with
      metabolic syndrome, insulin resistance, and non-alcoholic fatty liver disease,
      which are features often associated with PCOS. DESIGN: A cross-sectional analysis
      was performed between January 2010 and April 2012. SETTING: Unit of human
      reproductive pathophysiology, Catholic University Hospital. PATIENT(S): We
      prospectively analyzed 51 patients with psoriasis and 102 healthy age- and body
      mass index (BMI)-matched controls. INTERVENTION(S): None. MAIN OUTCOME
      MEASURE(S): The prevalence and characteristics of PCOS women of reproductive age
      with chronic plaque psoriasis. RESULT(S): The prevalence of PCOS was greater in
      patients with psoriasis than in matched control subjects (47.05% and 11.76%,
      respectively; odds ratio, 6.66; 95% confidence interval 2.95-15.07). Among the
      women with psoriasis, the prevalence of Psoriasis Area and Severity Index >=10
      was higher in patients with PCOS than in subjects without PCOS (odds ratio, 3.5;
      95% confidence interval 1.04-11.72). CONCLUSION(S): The prevalence of PCOS in
      women with psoriasis is remarkably greater than in age- and BMI-matched control
      women.

PMID- 23158934
TI  - Cellular uptake, antitumor response and tumor penetration of cisplatin-loaded
      milk protein nanoparticles.
AB  - The casein nanoparticles cross-linked by transglutaminase were prepared, and
      cisplatin (CDDP), as a model antitumor drug, was loaded into the casein
      nanoparticles. These nanoparticles were characterized by dynamic light scattering
      (DLS), transmission electron microscopy (TEM), and zeta potential. The uptake and
      penetration of nanoparticles in 2- and 3-dimensional SH-SY5Y cells were examined
      at 37  degrees C and 4  degrees C. The in vivo biodistribution of the
      nanoparticles was investigated using near-infrared fluorescence (NIRF) imaging
      and ion-coupled plasma mass spectrometry (ICP-MS). The antitumor effect of CDDP
      loaded nanoparticles was evaluated on hepatic H22 tumor-bearing mice model via
      intravenous administration. It is found that the obtained nanoparticles showed
      spherical shape with the size of 257 nm, and drug loading content of 10%. These
      CDDP-loaded casein nanoparticles have the extraordinary capabilities to penetrate
      cell membrane barriers, target tumor and inhibit tumor growth. The tumor growth
      inhibition of CDDP-loaded nanoparticles is 1.5-fold higher than that of free
      CDDP. Further, the penetration examination of the CDDP-loaded casein
      nanoparticles in the tumor tissue demonstrated that the nanoparticles had the
      ability to penetrate the tumor and deliver CDDP to the tumor more deeply and
      affect the cells far from the vasculature.

PMID- 23158936
TI  - [Use of zebrafish models for the research of traditional Chinese medicine].
AB  - Traditional Chinese medicine (TCM) exhibits a broad range of effects on
      biological activity that is probably due to interactions of complex chemical
      constituents with multiple targets in the body. Understanding the active chemical
      constituents in TCM is very important in providing rationales for the clinical
      usage of TCM. The zebrafish (Danio rerio) has recently become a popular model in
      the field of drug screening, specifically emerging as an important vertebrate
      model for in vivo high-content drug screening of multiple efficacy parameters and
      whole-organism toxicity. The authors also discussed the advantages of the
      zebrafish model for evaluating drug metabolism. Zebrafish usage in TCM screening
      should be a viable approach that helps identify active chemical markers,
      biological pathways and mechanistic actions of TCM.

PMID- 23158935
TI  - Hydrogels derived from central nervous system extracellular matrix.
AB  - Biologic scaffolds composed of extracellular matrix (ECM) are commonly used
      repair devices in preclinical and clinical settings; however the use of these
      scaffolds for peripheral and central nervous system (CNS) repair has been
      limited. Biologic scaffolds developed from brain and spinal cord tissue have
      recently been described, yet the conformation of the harvested ECM limits
      therapeutic utility. An injectable CNS-ECM derived hydrogel capable of in vivo
      polymerization and conformation to irregular lesion geometries may aid in tissue
      reconstruction efforts following complex neurologic trauma. The objectives of the
      present study were to develop hydrogel forms of brain and spinal cord ECM and
      compare the resulting biochemical composition, mechanical properties, and
      neurotrophic potential of a brain derived cell line to a non-CNS-ECM hydrogel,
      urinary bladder matrix. Results showed distinct differences between compositions
      of brain ECM, spinal cord ECM, and urinary bladder matrix. The rheologic modulus
      of spinal cord ECM hydrogel was greater than that of brain ECM and urinary
      bladder matrix. All ECMs increased the number of cells expressing neurites, but
      only brain ECM increased neurite length, suggesting a possible tissue-specific
      effect. All hydrogels promoted three-dimensional uni- or bi-polar neurite
      outgrowth following 7 days in culture. These results suggest that CNS-ECM
      hydrogels may provide supportive scaffolding to promote in vivo axonal repair.

PMID- 23158937
TI  - [A complexity analysis of Chinese herbal property theory: the multiple formations
      of herbal property].
AB  - Chinese herbal property theory (CHPT) is the fundamental characteristic of
      Chinese materia medica different from modern medicines. It reflects the herbal
      properties associated with efficacy and formed the early framework of four
      properties and five flavors in Shennong's Classic of Materia Medica. After the
      supplement and improvement of CHPT in the past thousands of years, it has
      developed a theory system including four properties, five flavors, meridian
      entry, direction of medicinal actions (ascending, descending, floating and
      sinking) and toxicity. However, because of the influence of philosophy about yin
      yang theory and five-phase theory and the difference of cognitive approach and
      historical background at different times, CHPT became complex. One of the
      complexity features was the multiple methods for determining herbal property,
      which might include the inference from herbal efficacy, the thought of Chinese
      Taoist School and witchcraft, the classification thinking according to
      manifestations, etc. Another complexity feature was the multiselection
      associations between herbal property and efficacy, which indicated that the same
      property could be inferred from different kinds of efficacy. This paper analyzed
      these complexity features and provided the importance of cognitive approaches and
      efficacy attributes corresponding to certain herbal property in the study of
      CHPT.

PMID- 23158938
TI  - Thinking on building the network cardiovasology of Chinese medicine.
AB  - With advances in complex network theory, the thinking and methods regarding
      complex systems have changed revolutionarily. Network biology and network
      pharmacology were built by applying network-based approaches in biomedical
      research. The cardiovascular system may be regarded as a complex network, and
      cardiovascular diseases may be taken as the damage of structure and function of
      the cardiovascular network. Although Chinese medicine (CM) is effective in
      treating cardiovascular diseases, its mechanisms are still unclear. With the
      guidance of complex network theory, network biology and network pharmacology,
      network-based approaches could be used in the study of CM in preventing and
      treating cardiovascular diseases. A new discipline-network cardiovasology of CM
      was, therefore, developed. In this paper, complex network theory, network biology
      and network pharmacology were introduced and the connotation of "disease-syndrome
      formula-herb" was illustrated from the network angle. Network biology could be
      used to analyze cardiovascular diseases and syndromes and network pharmacology
      could be used to analyze CM formulas and herbs. The "network-network"-based
      approaches could provide a new view for elucidating the mechanisms of CM
      treatment.

PMID- 23158939
TI  - [Systematic review and meta-analysis of randomized controlled trials of
      integrative medicine therapy for treatment of chronic severe hepatitis].
AB  - BACKGROUND: Chronic severe hepatitis is a critical disease with high mortality.
      Currently, effective drugs and therapy still lack. Comprehensive and supportive
      treatment, artificial liver and liver transplantation are the main therapies. A
      great number of studies on traditional Chinese medicine (TCM) in many ways
      combined with Western medicine treatment for chronic severe hepatitis have been
      reported, but the efficacy and safety still lack systematic evaluation.
      OBJECTIVE: To evaluate the efficacy and safety of integrative medicine therapy
      for chronic severe hepatitis. SEARCH STRATEGY: Literature was searched from
      PubMed, the Cochrane Library, the China National Knowledge Infrastructure
      Database, the Chongqing VIP Chinese Science and Technology Periodical Database,
      the Chinese Biomedical Literature Database and Wanfang Database. The time
      limitation ran from the commencement of each database to February 29, 2012.
      INCLUSION CRITERIA: Randomized controlled trials (RCTs) testing Chinese herbal
      medicine (CHM) combined with Western medicine (comprehensive and supportive
      treatment or artificial liver plasma exchange) against Western medicine were
      included. DATA EXTRACTION AND ANALYSIS: Two authors collected and extracted data
      independently. The methodological quality of literature was assessed by risk of
      bias table from Cochrane Collaboration and the data were analyzed by RevMan 5.1
      software. Heterogeneity of the included studies was checked by Chi-square test.
      The efficacy measure was relative risk (RR) or mean difference with a 95%
      confidence interval (CI). RESULTS: A total of 45 RCTs involving 4 449 patients
      with chronic severe hepatitis were included. Quality of all included trials was
      low. The oral CHM, enema and combined TCM with either Western medicine or plasma
      exchange were superior to Western medicine alone in improving total effective
      rate and reducing mortality with significant differences. In laboratory
      parameters, the integrative medicine treatment group was better than Western
      control group in reducing the total bilirubin and alanine aminotransferase, but
      two groups showed equal efficacy in lowering aspartate aminotransferase activity.
      The oral Chinese medicine combined with Western medicine or plasma exchange was
      better than Western medicine used alone in improving albumin synthesis and
      coagulation function, but Chinese medicine enema had no significant effect on the
      level of plasma albumin. The main side effects of the treatment group were
      abdominal pain, diarrhea and other intestinal symptoms after enema, while adverse
      reactions of the control group were mainly due to the plasma exchange.
      CONCLUSION: Integrated Chinese and Western medicine can promote the recovery of
      liver function and coagulation function, and reduce the mortality rate of
      patients with chronic severe hepatitis. However, due to a lower quality of
      clinical trials published in Chinese journals, the evidence is insufficient to
      prove the superiority of integrative therapy. Further well-designed, multicenter,
      large-sample RCTs are still needed to evaluate the beneficial effects of CHM.

PMID- 23158940
TI  - Three-factor designs unable to examine the interactions (part 2).
AB  - Three-factor designs that are unable to examine the interactions include
      crossover design and Latin square design, which can examine three factors: an
      experimental factor and two block factors. Although the two design types are not
      quite frequently used in practical research, an unexpected research effect will
      be achieved if they are correctly adopted on appropriate occasions. This article
      introduced the 3*3 crossover design and the Latin square design by examples.

PMID- 23158941
TI  - Qigong therapy for physiotherapists suffering from burnout: a preliminary study.
AB  - OBJECTIVE: The study was carried out in order to evaluate the prevalence of
      burnout in physiotherapists, and to assess whether "White Ball" Qigong exercises
      may be effective in burnout. This was aimed to provide preliminary data for the
      preparation and development of a larger study. METHODS: Physiotherapists
      completed a demographic questionnaire and the Maslach Burnout Inventory (MBI)
      questionnaire. For the intervention and the control groups, the authors selected
      those physiotherapists with the highest levels of burnout on the most important
      subscale. The intervention group (eight physiotherapists) performed a specific
      qigong intervention as developed by the Heidelberg School of Chinese Medicine;
      the control group consisted of eight physiotherapists on a waiting list. At the
      end of a three-week period of treatment or waiting list, both groups repeated the
      MBI for the comparison of results. RESULTS: Of 106 physiotherapists (36 males and
      70 females) assessed by the MBI, Emotional Exhaustion subscale was seen in 52
      (49.1%), Depersonalization subscale in 36 (33.9%), and Burnout in the Personal
      Accomplishment subscale in 33 (31.2%), of whom 4 (3.8%) suffered to a severe
      degree and 29 (27.4%) moderately. Within the study group qigong lowered the mean
      values of Emotional Exhaustion subscale from 38.0 to 31.4, whereas in the control
      group the values rose from 33.9 to 37.9. The differences between the two groups
      were statistically significant (P=0.023). Qigong lowered the mean value of
      Depersonalization subscale from 10.8 to 6.8. In controls the value rose from 7.3
      to 10.6. The difference between the two groups was statistically significant
      (P=0.013). The mean values of Personal Accomplishment subscale decreased in both
      groups: from 35.4 to 33.9 in the intervention group, and from 37.5 to 37.1 in the
      control group. The difference between the two groups was not statistically
      significant. CONCLUSION: The effects of "White Ball" Qigong on burnout symptoms
      are measurable by the MBI. The results are compatible with the thesis that this
      type of qigong is an effective tool for the self-management of burnout. It is
      easy to integrate into a daily routine as it takes only 2*5 min per day. On the
      basis of this evaluation, a study design can now be developed on a larger scale
      with appropriate blinding, follow-up testing and adequate controls.

PMID- 23158942
TI  - Effects of Chinese medicine for promoting blood circulation and removing blood
      stasis in treating patients with mild to moderate vascular dementia: a
      randomized, double-blind and parallel-controlled trial.
AB  - BACKGROUND: Vascular dementia (VaD) is the second common subtype of dementia
      after Alzheimer's disease. However, there is still a lack of medication that
      demonstrates clinically relevant symptomatic improvement. Static blood
      obstructing the brain is the main Chinese medicine syndrome of VaD. OBJECTIVE: To
      evaluate the effects of Chinese medicine for promoting blood circulation and
      removing blood stasis in patients with mild to moderate VaD. DESIGN, SETTING,
      PARTICIPANTS AND INTERVENTIONS: In this 12-week randomized, double-blind,
      parallel-controlled trial, a total of 48 patients with mild to moderate VaD were
      enrolled between March 2009 and December 2010. All the patients entered a two
      week placebo run-in period followed by a 12-week treatment with Chinese medicine
      for promoting blood circulation and removing blood stasis (n=24) or placebo
      (n=24), respectively. The placebo tablets have the identical taste and appearance
      as the Chinese medicine tablets. MAIN OUTCOME MEASURES: The primary outcome
      measure was the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS
      cog); the secondary outcome measures included the Activities of Daily Living
      (ADL) and the Mini-Mental State Examination (MMSE). RESULTS: The Chinese medicine
      group showed a slight deterioration of 0.25 points and the placebo group showed a
      deterioration of 2.35 points from baseline by the ADAS-cog, and there was a
      significant difference between the two groups (P=0.027). The ADL and the MMSE
      showed no significant difference from baseline in both groups. Adverse events
      were rare in both groups. CONCLUSION: The Chinese medicine for promoting blood
      circulation and removing blood stasis may improve cognition and it is safe and
      well tolerated.

PMID- 23158943
TI  - [Effects of early application of Tuina treatment on quadriceps surface
      myoelectricity in patients after total knee arthroplasty: a randomized controlled
      trial].
AB  - BACKGROUND: Total knee replacement surgery is commonly used in end-stage diseases
      of the knee. It is important for improving surgical efficacy and patient
      satisfaction by promoting early rehabilitation of patients and improving knee
      function. OBJECTIVE: To observe the effects of early application of Tuina
      treatment on quadriceps surface electromyography (EMG) in patients with
      rheumatoid arthritis having undergone total knee arthroplasty. DESIGN, SETTING,
      PARTICIPANTS AND INTERVENTION: The study was performed at the Orthopedic
      Department of Huashan Hospital, Fudan University, and the Shanghai Guanghua
      Hospital of Integrated Traditional Chinese and Western Medicine from June 2010 to
      September 2011. A total of 66 patients with rheumatoid arthritis who had
      undergone total knee replacement surgery were randomly divided into control group
      and observation group, 33 cases in each. The patients in the control group were
      administered with continuous passive training (CPM), and the patients in the
      observation group were treated with CPM combined with Tuina, from prior surgery
      to four weeks post-surgery. MAIN OUTCOME MEASURES: The knee function was
      evaluated using the Western Ontario and McMaster Universities Osteoarthritis
      Index (WOMAC) questionnaire at baseline and 4 weeks after the surgery. Quadriceps
      surface EMG was also detected at the same time points. RESULTS: After 4 weeks of
      Tuina and comprehensive rehabilitation intervention, the WOMAC questionnaire
      score of the observation group was decreased compared with the control group
      (P<0.01); median frequency and integrated electromyography of the rectus femoris
      and vastus medialis muscles, which were recorded by EMG, in the observation group
      were higher than those in the control group (P<0.01). CONCLUSION: Tuina can
      improve the recovery of patients who have undergone total knee replacement by
      increasing quadriceps EMG.

PMID- 23158944
TI  - [Quantitative evaluation of the degrees of traditional Chinese medicine
      qualitative syndromes of osteoporosis].
AB  - OBJECTIVE: To establish a quantitative estimate model for diagnosing traditional
      Chinese medicine (TCM) syndromes of patients with osteoporosis. METHODS: Symptoms
      and signs of osteoporosis and methodology related to syndrome research were
      collected by reviewing medical literature. The symptoms and sighs were
      quantitatively classified into three, two or one category according to a 100-mm
      visual analog scale. Fuzzy comprehensive evaluation model of TCM qualitative
      syndromes was performed based on analytic hierarchy process. Then "Hall for
      Workshop of Metasynthetic Engineering" expert symposium was held on subjects of
      syndrome quantification method and weight of evaluation indices in different
      levels for developing the analysis model of common syndromes. For clinical
      verification, the created models were applied to patients with osteoporosis for
      discriminating syndromes. Syndrome of each patient was also identified by 8
      experts major in integrative medicine treating osteoporosis for comparing the
      coincidence rate using a self-made clinical questionnaire. RESULTS: Through
      literature reviewing, symptoms and signs quantification and expert discussing,
      the authors formed estimate models of essence deficit, qi deficiency, yin
      deficiency, yang deficiency, and blood stasis. A total of 220 patients with
      osteoporosis were enrolled and filled the clinical questionnaire. All 8 experts
      completed and returned the questionnaire (1 760 cases), and 1 545 of them were
      filled in completely. Experts' opinion on syndrome differentiation was exactly
      coincidence to estimate model in 611 cases and almost coincidence in 639 cases.
      The total coincidence rate reached to 94.05%. CONCLUSION: The estimate model for
      syndrome differentiation of osteoporosis has a high-coincidence rate with the
      fuzzy evaluation from experts, with good rationality and feasibility, and is
      worthy of promotion in the clinical study.

PMID- 23158945
TI  - [Chromaticity and optical spectrum colorimetry of the tongue color in different
      syndromes of primary hepatic carcinoma].
AB  - OBJECTIVE: In this study, the optical data of tongue color of different syndromes
      in primary hepatic carcinoma (PHC) were detected by optical spectrum colorimetry,
      and the chromaticity of tongue color was compared and analyzed. The tongue color
      characteristics of different syndromes in PHC and the relationship between
      different syndromes and tongue color were also investigated. METHODS: Tongue
      color data from 133 eligible PHC patients were collected by optical spectrum
      colorimetry and the patients were divided into 4 syndrome groups according to
      their clinical features. The syndrome groups were liver depression and spleen
      deficiency (LDSD), accumulation of damp-heat (ADH), deficiency of liver and
      kidney yin (DLKY), and qi stagnation and blood stasis (QSBS). The variation
      characteristics of chromaticity coordinates, dominant wavelength, excitation
      purity and the distribution in the International Commission on Illumination (CIE)
      LAB uniform color space were measured. At the same time, the differences of
      overall chromatism, clarity, chroma, saturation and hue were also calculated and
      analyzed. RESULTS: PHC patients in different syndrome groups exhibited
      differences in chromaticity coordinates. The dominant wavelength of QSBS was
      distinctly different from that of the other 3 syndromes. Excitation purity in the
      syndromes of LDSD, ADH and DLKY showed gradual increases (P<0.01). Different
      syndromes in the CIE LAB color three-dimensional space showed differences in
      tongue color distribution areas. The CIE hue-angle value of QSBS was negative,
      and different from that of the other 3 syndromes (P<0.01). CIE chroma in the
      syndromes of LDSD, ADH and DLKY showed gradual increases (P<0.01), the same as
      excitation purity. In the comparison of chromatism, tongue color variations in
      different syndromes were quantified by human observation. CONCLUSION: This study
      shows that tongue color diagnosis according to the syndrome classifications of
      traditional Chinese medicine can be quantified with optical spectrum colorimetry
      technology. Different syndromes in PHC exhibit distinct chromatisms of tongue
      color through the calculation and analysis of chromaticity parameters of CIE,
      combined with colorimetric system and CIE LAB color space, and these are
      consistent with the characteristics of clinical tongue color. Applying optical
      spectrum colorimetry technology to tongue color differentiation has the potential
      to serve as a reference point in standardizing traditional Chinese medicine
      syndrome classification in PHC.

PMID- 23158946
TI  - [Analysis of the osteogenetic effects exerted on mesenchymal stem cell strain
      C3H10T1/2 by icariin via MAPK signaling pathway in vitro].
AB  - OBJECTIVE: To investigate the effects of icariin, an effective extract from
      traditional Chinese medicine Epimedium pubescens with the function of tonifying
      kidney, in promoting osteogenesis of mesenchymal stem cell line C3H10T1/2, and to
      explore the underlying mechanism. METHODS: After culture with icariin (0, 10(-7),
      10(-6), 10(-5), and 10(-4) mol/L) and osteogenic supplement for 26 d in vitro,
      osteogenic differentiation of C3H10T1/2 cells was detected by alkaline
      phosphatase (ALP) assay. The RNA was extracted from cells cultured with 10(-5)
      mol/L icariin for 2, 8, 24 and 48 hours, and mRNA expressions of p38, p42 and p44
      were measured using real-time reverse transcription-polymerase chain reaction
      (PCR) method. Three main proteins of MAPK signaling pathway (p38, and
      extracellular signal-regulated protein kinase (ERK), also named p42/44) and c-Jun
      N-terminal kinase (JNK) and their phospho-products were examined using Western
      blotting after icariin treatments of 10, 30, 60 and 120 min. RESULTS: Icariin at
      a dose of 10(-5) mol/L, when combined with the osteogenic supplement, had the
      best ability to promote osteogenic differentiation on C3H10T1/2 cells. Based on
      real-time PCR, the authors found that after two-hour ICA treatment, the gene
      expression of p38 revealed a significant decline compared with the control group
      (P<0.01). The levels of p42 and p44 mRNAs were decreased greatly after two-hour
      ICA treatment, while increased after 48-hour ICA treatment (P<0.05, P<0.01).
      There was no significant difference at other time points (P>0.05). Phospho-p42
      was decreased after 10-minute icariin treatment, while phospho-p38 expression
      displayed an increase after 10- and 30-minute of treatment with icariin. There
      was no notable difference in phospho-JNK expression at these four time points.
      CONCLUSION: Icariin promotes differentiation of the mesenchymal stem cells
      C3H10T1/2 into osteoblasts, and its effect is related to the restraining of ERK
      expression and activation of p38 expression in the MAPK signaling pathway.

PMID- 23158947
TI  - [Effects of Chinese herbal medicine Danzhi Jiangtang Capsule and exercise on JNK
      signaling pathway in pancreatic tissues of diabetic rats].
AB  - OBJECTIVE: To explore the effects of exercise and Danzhi Jiangtang Capsule (DJC),
      a compound traditional herbal medicine, on the JNK signaling pathway in
      pancreatic tissues of diabetic rats and to investigate the possible mechanisms of
      exercise and DJC in treating diabetes. METHODS: Seventy-eight male Wistar rats
      were injected with low dose of streptozotocin and fed a high-fat diet to
      establish a diabetic model in rats. Then 60 diabetic rats were divided into
      diabetes group, exercise group, DJC group and exercise combined with DJC group.
      Another twelve rats were used as normal control. After eight months of treatment,
      the expression levels of phosphor-c-Jun N-terminal kinase (p-JNK), pancreatic and
      duodenal homeobox-1 (PDX-1), and insulin protein in pancreatic tissues from rats
      were detected by immunohistochemical method and Western blotting. RESULTS: In
      pancreatic tissues of diabetes group, the expression level of p-JNK protein was
      significantly higher than that in the normal group (P<0.01), and the expression
      levels of PDX-1 and insulin protein were significantly decreased (P<0.01). After
      administration of exercise and DJC, the expression level of p-JNK protein in
      pancreatic tissues of the diabetes group was decreased significantly, while the
      expression levels of PDX-1 and insulin protein were increased significantly
      (P<0.05 or P<0.01). CONCLUSION: Exercise and DJC effectively protect isletbeta
      cell function in diabetic rats, which might be due to a decreased JNK signaling
      pathway.

PMID- 23158948
TI  - [Effects of Chinese herbal medicine Xiaopi Pill in preventing rats from
      dimethylnitrosamine-induced liver fibrosis].
AB  - OBJECTIVE: To explore the intervention effects of Xiaopi Pill (XPW), a compound
      traditional Chinese herbal medicine, on the development progress of
      dimethylnitrosamine (DMN)-induced liver fibrosis in rats. METHODS: Liver fibrosis
      model was established by intraperitoneal injection of 0.5% DMN 2 mL/kg thrice a
      week for 4 weeks. Rats were divided into control group given saline and treatment
      group given XPW during the 3rd week of DMN injections. Rats were sacrificed at
      the end of the experiment, and then liver histological changes, liver function
      and mRNA expression of the liver fibrosis-associated markers were observed.
      RESULTS: (1) At the end of the 2nd and 4th weeks of DMN injection, serum levels
      of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline
      phosphatase (ALP) increased significantly in rats (P<0.01 or P<0.05); content of
      total bilirubin (TBil) increased significantly compared with the normal group
      until the end of the 4th week (P<0.05); compared with the model group after 4
      weeks of DMN injection, the serum levels of ALT, AST, ALP and TBil were decreased
      remarkably in the XPW-treated group (P<0.01 or P<0.05). (2) The hepatic
      inflammation and collagen deposition in hepatic tissues increased by different
      degrees in experimental rats. Parts of pathological changes in the rat liver were
      found at the end of the 4th week, including a complete round structure of false
      flocculus round, meantime, the hydroxyproline content of hepatic tissue was
      increased significantly at the end of the 2nd and 4th weeks (P<0.05). Compared
      with the 4-week model group, the hepatic inflammation, collagen deposition and
      hydroxyproline content in hepatic tissues were alleviated dramatically (P<0.05).
      (3) Compared with the normal and 2nd week groups, protein expression of alpha
      smooth muscle actin (alpha-SMA) was gradually increased, and that of the 4th week
      group were aggrandized significantly (P<0.01). Compared with the normal group,
      the mRNA expression of alpha-SMA, transforming growth factor-beta1 (TGF-beta1),
      tissue inhibitor of metalloproteinase-1 (TIMP-1), and heme oxygenase-1 (HO-1) was
      gradually increased. Further changes in above-mentioned abnormalities were found
      in the model rats at the end of the 4th week (P<0.01); while compared to the 4th
      week group, protein and mRNA levels of alpha-SMA and mRNA levels of TGF-beta1,
      TIMP-1, and HO-1 were decreased significantly in the XPW group (P<0.01 or
      P<0.05). CONCLUSION: Progressive DMN-induced liver fibrosis in rats can be
      suppressed by XPW; the mechanism may be associated with inhibition of the
      activated hepatic stellate cells.

PMID- 23158949
TI  - Ameliorative potentials of Syzygium jambolanum extract against arsenic-induced
      stress in L6 cells in vitro.
AB  - OBJECTIVE: To determine the ameliorative potentials of Syzygium jambolanum (SJ)
      extract in L6 skeletal muscle cells in regard to arsenic-induced impairment of
      optimum glucose homeostasis and improper functioning of mitochondria. METHODS:
      Several study parameters like glucose level and mitochondrial functioning through
      indexes of pyruvate kinase, glucokinase and mitochondrial membrane potential were
      assessed. The expression of the relevant marker proteins and mRNAs like glucose
      transporter 4 (GLUT4), insulin receptor substrate 1 (IRS1), IRS2 and glucokinase
      for tracking down the signalling cascade were critically analyzed. RESULTS:
      Introduction of SJ extract could bring about positive modulation of various
      markers, by acting on GLUT4, thereby bringing about an attenuation of the
      arsenite-induced toxic conditions in L6 cells. CONCLUSION: Syzygium jambolanum
      extract has considerable ameliorating potentials against arsenic-induced glucose
      imbalance and stress and has possibility of therapeutic use in the management of
      arsenic-induced toxicity including hyperglycemia.

PMID- 23158950
TI  - Antihepatotoxic activity of Euphorbia neriifolia extract against N
      nitrosodiethylamine-induced hepatocarcinogenesis in mice.
AB  - OBJECTIVE: To scrutinize the protective role of hydroethanolic extract of
      Euphorbia neriifolia leaves (HEEN) against N-nitrosodiethylamine (DENA)-induced
      hepatocarcinogenesis in male Swiss albino mice. METHODS: Experimental mice were
      pretreated with 150 and 400 mg/kg of HEEN, or 0.5% and 1% of butylated
      hydroxyanisole (BHA) as a standard for 14 d prior to the administration of a
      single dose of 50 mg/kg of DENA. Levels of xenobiotic metabolizing enzymes such
      as cytochrome (Cyt) P450 and Cyt b5, activities of reduced glutathione (GSH),
      glutathione-S-transferase (GST), aspartate amino transaminase (AST), alanine
      amino transaminase (ALT) and alkaline phosphatase (ALP), and total protein and
      cholesterol content in the liver tissues were measured to determine the
      hepatotoxicity caused by DENA. RESULTS: The levels of Cyt P450 and Cyt b5 were
      significantly increased, and GST and GSH were significantly depleted after DENA
      treatment (P<0.01). The activities of AST, ALT and ALP, and the total protein
      content were also significantly dropped off (P<0.01). The total cholesterol level
      was markedly increased by DENA as compared with the normal group (P<0.01).
      However, the pre-supplementation of HEEN showed a remarkable amelioration of
      these abnormalities, and the levels of the antioxidant enzymes in the liver were
      significantly restored, which exhibited the dose-dependent protective effect
      against DENA-induced hepatotoxicity. CONCLUSION: HEEN exerts its chemopreventive
      effects by alleviating the xenobiotic enzymes and enhancing the levels of
      antioxidants and biochemical assays in DENA-induced carcinogenesis by reducing
      the formation of free radicals.

PMID- 23158951
TI  - Comparative study on WHO Western Pacific Region and World Federation of Chinese
      Medicine Societies international standard terminologies on traditional medicine:
      diseases in internal medicine (part 7).

PMID- 23158952
TI  - English translation of cultural aspects of the titles of traditional Chinese
      medicine classics based on the skopos theory.

PMID- 23158953
TI  - Double pancreatic and gastric adenocarcinomas: a rare association.
AB  - Synchronous gastric and pancreatic cancers represent a very rare association. The
      role of tomodensitometry, endoscopic ultrasound and histology is primordial to
      differentiate between double tumors, local extension or metastasis. We report in
      our paper two cases of synchronous gastric and pancreatic cancers treated with
      Folforinox. Then, we discuss the risk factors, the diagnostic methods, the
      treatment modalities and the prognosis of these rare double cancers. 

PMID- 23158954
TI  - 50 practical medication tips at end of life.
AB  - Patients with a life-limiting illness frequently experience pain and other
      symptoms. It is important to pay close attention when medication therapy is used
      to manage these symptoms. Occasionally, practitioners need to be creative in
      selecting, dosing, administering, and discontinuing medications at the end of
      life because of the patient's changing health care needs. This article offers
      practical end-of-life medication tips including, but not limited to, medication
      administration; guidance on how to increase and decrease doses; medication
      selection for difficult-to-treat patients; alternative dosage formulations;
      routes of medication administration; debridement medication regimens; and
      appropriate drug therapy selection.

PMID- 23158955
TI  - One size does not fit all: the different experiences of those with chronic heart
      failure, type 2 diabetes and chronic obstructive pulmonary disease.
AB  - INTRODUCTION: The Australian federal government is developing a policy response
      to chronic disease in Australia. The Serious and Continuing Illness Policy and
      Practice Study examined the experience of individuals with chronic heart failure
      (CHF), chronic obstructive pulmonary disease (COPD) or type 2 diabetes mellitus
      (diabetes) in the Australian Capital Territory (ACT) and Western Sydney. This
      paper describes the disease-specific experiences of people interviewed. METHODS:
      We conducted semi-structured interviews with 40 individuals aged 45-85 years with
      CHF, COPD or diabetes in 2008. Interviews were recorded and transcribed.
      Qualitative content analysis was performed, assisted by QSR Nvivo 8 qualitative
      data software. RESULTS: Participants with CHF (n=9) came to terms with the
      prospect of unpredictable sudden death. Participants with COPD (n=15) were angry
      about limitations it imposed on their lives. Participants with diabetes (n=16)
      experienced a steep learning curve in self-management of their condition
      surrounded by high levels of uncertainty. CONCLUSION: Although people with
      chronic illness share many experiences, a person's overall experience of living
      with chronic illness is significantly shaped by the nature of their specific
      dominant disease. Policies for patient-centred care must take account of both
      generic and disease-specific elements.

PMID- 23158956
TI  - Prevention of injuries and diseases in non-professional disaster volunteer
      activities in the Great East Japan Earthquake areas: a preliminary study.

PMID- 23158957
TI  - A sex- and gender-based analysis of allostatic load and physical complaints.
AB  - BACKGROUND: Biological sex and sociocultural gender influence stress-related
      diseases. Our goal was to explore whether sex and gender roles would predict both
      allostatic load and physical complaints. OBJECTIVE: This study investigated
      whether sex- and gender-based factors would correspond to objective and
      subjective health outcomes. METHODS: Thirty Montreal workers (mean [SE] age, 45.4
      [2.1] years) participated. The 30-item Bem Sex Role Inventory was administered to
      assess scores for masculinity and femininity, which were then transformed into an
      androgyny index representing gender roles along a continuum. Fifteen biomarkers
      representing neuroendocrine, immune, metabolic, and cardiovascular systems were
      aggregated into an allostatic load index measuring physiological dysregulations.
      The 42-item Wahler Physical Symptoms Inventory was used to measure self-rated
      physical complaints. RESULTS: Results using logistic and linear regressions
      controlling for age revealed that increased masculinity predicted inclusion in
      the high allostatic load group (P = 0.010; odds ratio = 0.715), and sex did not;
      increased masculinity and female sex together predicted increased physical
      complaints (P = 0.008; adjusted r(2)= 0.30); and high allostatic load group
      membership corresponded to increased physical complaints adjusted (P = 0.001;
      adjusted r(2) = 0.301). CONCLUSIONS: That higher masculinity was related to
      increased objective physiological dysregulations and subjective physical
      complaints suggests an increased vulnerability to hyperarousal pathologies, such
      as cardiovascular disease, among masculine-typed individuals.

PMID- 23158958
TI  - A comprehensive analysis of features that suggest bipolarity in patients with a
      major depressive episode: which is the best combination to predict soft
      bipolarity diagnosis?
AB  - BACKGROUND: The study aimed to identify specific predictors of soft bipolarity
      (bipolar II disorder or bipolar disorder not otherwise specified) in depressed
      patients and to evaluate the global predictive performance of combinations of
      these predictors. METHODS: Subjects included 199 patients with a major depressive
      episode (MDE) due to soft bipolarity or major depressive disorder. Independent
      predictors of soft bipolar diagnosis were extracted from 12 previously proposed
      bipolar features using multiple logistic regression analyses, and the global
      performance of the combination of these predictors was evaluated using a receiver
      operating characteristic (ROC) curve. RESULTS: Recurrent MDEs, family history of
      bipolar disorders in first-degree relatives, cyclothymic temperament, early age
      at onset of first MDE, and depressive mixed state were independent predictors of
      soft bipolarity diagnosis [odds ratio (95% confidence interval): 11.22 (2.19
      57.63), 8.82 (1.31-59.15), 7.32 (2.22-24.19), 6.22 (1.58-24.57), and 5.57 (1.91
      16.30), respectively]. The area under the ROC curve for the relationship between
      soft bipolarity diagnosis and the number of these five predictors in each patient
      was 0.911 (highly accurate). The presence of one or more predictors in each
      patient resulted in highest sensitivity (92.5%) and good specificity (73.1%),
      whereas that of two or more predictors resulted in good sensitivity (70.0%) and
      highest specificity (97.5%) for soft bipolarity diagnosis. LIMITATIONS:
      Structured/semistructured interviews were not used. Tools for temperament
      assessments were different between institutions. CONCLUSIONS: A combination of
      these predictors was quite helpful for a precise diagnosis of soft bipolarity in
      patients with depression.

PMID- 23158959
TI  - Poor health-related quality of life prior to ECT in depressed patients normalizes
      with sustained remission after ECT.
AB  - BACKGROUND: Health-related quality of life (HRQOL) is diminished in depressed
      adult outpatients and especially impaired among depressed patients referred for
      ECT. We compare pretreatment HRQOL in ECT and non-ECT depressed patients from two
      large samples, and examined whether sustained remission in depressive symptoms
      after ECT is associated with normalization of HRQOL. METHODS: HRQOL was measured
      with the Medical Outcomes Study Short Form 36 (SF36) before ECT and 6 months
      after ECT in an effectiveness (n=286) and an efficacy (n=243) clinical trial.
      RESULTS: ECT patients had very low baseline SF36 scores. With one exception, SF36
      subscale scores in both trials were significantly lower than those of depressed
      outpatients. A minority of patients in both trials entered and sustained
      remission over the 24 week timeframe. Among sustained remitters, average SF36
      scores were no different from normative scores of the general adult population,
      except that in the effectiveness study ECT patients reported less Bodily Pain
      (p<0.05) and better Mental Health (p<0.05), while in the efficacy study ECT
      patients reported more difficulty with Role-Emotional (p<0.01). LIMITATIONS: Only
      a modest number of patients were observed in sustained remission. CONCLUSIONS:
      HRQOL is very poor in patients referred for ECT. Depressed patients who
      experience sustained remission after ECT, however, can expect improvement in
      their quality of life that leaves many in a position indistinguishable from the
      general adult population.

PMID- 23158960
TI  - Emotional expression and socially modulated emotive communication in children
      with traumatic brain injury.
AB  - Facial emotion expresses feelings, but is also a vehicle for social
      communication. Using five basic emotions (happiness, sadness, fear, disgust, and
      anger) in a comprehension paradigm, we studied how facial expression reflects
      inner feelings (emotional expression) but may be socially modulated to
      communicate a different emotion from the inner feeling (emotive communication, a
      form of affective theory of mind). Participants were 8- to 12-year-old children
      with TBI (n = 78) and peers with orthopedic injuries (n = 56). Children with mild
      moderate or severe TBI performed more poorly than the OI group, and chose less
      cognitively sophisticated strategies for emotive communication. Compared to the
      OI and mild-moderate TBI groups, children with severe TBI had more deficits in
      anger, fear, and sadness; neutralized emotions less often; produced socially
      inappropriate responses; and failed to differentiate the core emotional dimension
      of arousal. Children with TBI have difficulty understanding the dual role of
      facial emotions in expressing feelings and communicating socially relevant but
      deceptive emotions, and these difficulties likely contribute to their social
      problems.

PMID- 23158961
TI  - Severe lactose intolerance in a patient with coronary artery disease and ischemic
      cardiomyopathy.
AB  - A 72-year-old man with severe lactose intolerance was admitted for non-ST-segment
      elevation myocardial infarction. The coronary angiogram revealed occlusion of the
      distal third of the first diagonal artery and several non-significant lesions.
      The pre-discharge echocardiogram revealed moderate left ventricular systolic
      dysfunction. Discharged on dual antiplatelet therapy, rosuvastatin, perindopril
      and carvedilol, he was repeatedly readmitted in the following days for abdominal
      pain/bloating, diarrhea and nausea despite avoiding food products containing
      lactose. To date, there has been no comprehensive study on the relationship
      between lactose intolerance and coronary disease, nor has its impact on
      therapeutics been appropriately addressed. Intolerance to lactose-containing
      prescription medicines is an extremely rare phenomenon and few strategies are
      available to overcome this condition, as it has received little attention from
      the scientific community. Commercial forms of the lactase enzyme and probiotics
      can limit symptom severity, but different routes of administration, different
      brands of the same medicine or completely different medicines may be necessary.
      Some measures were proposed to our patient and, soon afterwards, he was
      completely asymptomatic in both gastrointestinal and cardiovascular terms.

PMID- 23158962
TI  - Does metabolic syndrome predict significant angiographic coronary artery disease?
AB  - INTRODUCTION: Metabolic syndrome (MS) is an independent predictor of acute
      cardiovascular events. However, few studies have addressed the relationship
      between MS and stable angiographic coronary artery disease (CAD), which has a
      different pathophysiological mechanism. We aimed to study the independent
      predictors for significant CAD, and to analyze the impact of MS (by the AHA/NHLBI
      definition) on CAD. METHODS: We prospectively included 300 patients, mean age
      64+/-9 years, 59% male, admitted for elective coronary angiography (suspected
      ischemic heart disease), excluding patients with known cardiac disease. All
      patients underwent assessment of demographic, anthropometric, and laboratory data
      and risk factors, and subsequently underwent coronary angiography. RESULTS: In
      the study population, 23.0% were diabetic, 40.5% had MS (and no diabetes) and
      36.7% had neither diagnosis. Significant CAD was present in 51.3% of patients.
      CAD patients were older and more frequently male and diabetic, with increased
      triglycerides and glucose and lower HDL cholesterol. Abdominal obesity was also
      less prevalent. MS was not associated with the presence of CAD (OR 0.94, 95% CI
      0.59-1.48, p=0.778). Of the MS components, the most important predictors of CAD
      were increased glucose and triglycerides. Abdominal obesity was associated with a
      lower risk of CAD. In a multivariate logistic regression model for CAD,
      independent predictors of CAD were age, male gender, glucose and triglycerides.
      Body mass index had a protective effect. CONCLUSIONS: Although MS is associated
      with cardiovascular events, the same was not found for stable angiographically
      proven CAD. Age, gender, diabetes and triglycerides are the most influential
      factors for CAD, with abdominal obesity as a protective factor.

PMID- 23158963
TI  - [Celebrating the 10th anniversary of the Portuguese Cardiology Data Collection
      Center: a reflexion on its past, present, and future].

PMID- 23158964
TI  - Twiddler syndrome as a cause of defibrillator malfunction.

PMID- 23158965
TI  - Comparing biobehavioral profiles across two social stress paradigms in children
      with and without autism spectrum disorders.
AB  - BACKGROUND: Autism spectrum disorders (ASD) are defined by impairment in
      reciprocal social interaction and flexible adaptation to the environment. This
      study compared physiological stress in children with and without ASD exposed to
      two social stress protocols. We hypothesized that the ASD group would show
      heightened initial and enduring cortisol levels to the social stressors, which
      would be moderated by age and intelligence. METHODS: Twenty-seven children with
      ASD and 32 with typical development (TYP) completed a standardized social
      evaluative performance task and a validated paradigm of social play with peers.
      Physiological stress was measured by salivary cortisol at nine time points.
      Statistical approaches included repeated-measures linear mixed models and
      correlation analyses. RESULTS: The average cortisol level of both groups during
      initial exposure to social situations was significantly greater than baseline
      levels (ASD, P = 0.018; TYP, P = 0.006). Stress responsivity was significantly
      different between the groups; the TYP group showed a significant reduction in
      cortisol over time (P = 0.023), whereas the ASD group maintained an elevated
      cortisol level (P >0.05). The ASD group evidenced greater variability in between
      group, within-group and intra-individual analyses. Age was a positive moderator
      of stress for the ASD group (P = 0.047), whereas IQ was a negative moderator for
      the TYP group (P = 0.061). CONCLUSIONS: Initial stress to novel social scenarios
      is idiosyncratic and predictive of subsequent exposure. Amidst significant
      variability in cortisol, children with ASD show enhanced and sustained social
      stress that increases with age. Developmental and cognitive factors
      differentially moderate stress in children with ASD and TYP, respectively. A
      model of neuroendocrine reactivity is proposed.

PMID- 23158966
TI  - Validation of a novel sham cervical manipulation procedure.
AB  - BACKGROUND CONTEXT: No clinical trial of spinal manipulation for chronic neck
      pain (NP), for either single or multiple intervention session(s), has used an
      effective manual sham-manipulation control group. PURPOSE: Validate a practical
      sham cervical high-velocity low-amplitude spinal manipulation. STUDY
      DESIGN/SETTING: Randomized experimental validation study in an institutional
      clinical research laboratory. PATIENT SAMPLE: Eligible subjects were males and
      females, 18 to 60 years of age with mechanical NP (as defined by the
      International Association for the Study of Pain Classification) of at least 3
      months' duration. Subjects with arm pain, any pathologic cause of NP, or any
      contraindication to spinal manipulation were excluded. OUTCOME MEASURES: The
      primary outcome was the patient's self-report or registration of group allocation
      after treatment. Secondary outcomes were numerical rating scale-101 for NP, range
      of motion (ROM; by goniometer), and tenderness (by pressure algometry). METHODS:
      Eligible subjects were randomly allocated to one of two groups: real cervical
      manipulation (RM) or sham cervical manipulation (SM). All subjects were given two
      procedures in sequence, either RM+SM or SM+SM. Immediately after the two
      procedures, subjects were asked to register any pain experienced during the
      procedures and to identify their treatment group allocation. Force-time profiles
      were recorded during all procedures. Secondary clinical outcome measures were
      obtained at baseline, 5 and 15 minutes after the intervention, including ROM,
      self-report of pain, and local spinous process tenderness. Data for each variable
      were summarized and tested for normality in distribution. Summary statistics were
      obtained for each variable and statistically tested. RESULTS: Sixty-seven
      subjects were randomized. Data from 64 subjects (32 per group) were available for
      analysis. There were no significant differences between the groups at baseline.
      One adverse event occurred in the "real" group, which was a mild posttreatment
      pain reaction lasting less than 24 hours. In the RM group, 50% of subjects
      incorrectly registered their treatment allocation; in the sham group, 53% did so.
      For the SM group, none of the procedures resulted in cavitation, whereas in the
      RM group, 87% of procedures resulted in cavitation. There were no significant
      changes between groups on pain, tenderness, or ROM. Force-time profiles of the RM
      and SM procedures demonstrated fidelity with significant differences between
      components as intended. CONCLUSIONS: The novel sham procedure has been shown to
      be effective in masking subjects to group allocation and to be clinically inert
      with respect to common outcomes in the immediate posttreatment stage. Further
      research on serial applications and for multiple operators is warranted.

PMID- 23158967
TI  - Factors affecting the occurrence of pulmonary embolism after spinal surgery: data
      from the national administrative database in Japan.
AB  - BACKGROUND CONTEXT: Despite potentially devastating consequences, pulmonary
      embolism (PE) in patients undergoing spinal surgery remains poorly understood. To
      the best of our knowledge, few large studies have examined the prevalence and
      risk factors of PE after spinal surgery. PURPOSE: To investigate the prevalence
      of symptomatic PE in patients undergoing elective spinal surgery and to identify
      clinical variables associated with the occurrence of postoperative PE. STUDY
      DESIGN: A retrospective analysis of data abstracted from the diagnosis procedure
      combination (DPC) database, a nationally representative database in Japan.
      PATIENT SAMPLE: We included all patients with a diagnosis of spinal canal
      stenosis, disc herniation, spondylosis, spondylolisthesis, trauma, metastatic
      tumor, or infection who underwent spinal surgery between July 1 and December 31
      of 2007 and 2008, respectively. OUTCOME MEASURES: The primary end point was
      defined as the occurrence of postoperative PE during hospitalization. The
      secondary end point was in-hospital death after postoperative PE. METHODS: We
      analyzed the association between the occurrence of postoperative PE and clinical
      variables recorded in the DPC database, including age, sex, comorbidities,
      location of surgery, primary diagnosis, anterior/posterior approach, use of
      instrumentation, and duration of anesthesia. RESULTS: A total of 47,743 patients
      were identified. Of these, 50 (0.10%) developed PE and four died as a result of
      PE. Logistic regression analyses revealed that occurrence of PE was associated
      with older age (70 years or older; odds ratio [OR], 3.15; 95% confidence interval
      [CI], 1.15-8.69; p=.026) and longer anesthesia time (more than 360 minutes; OR,
      2.19; 95% CI, 0.88-5.44; p=.092). Patients with trauma were significantly more
      likely to have a PE than those with spinal canal stenosis (0.27% vs. 0.09%; OR,
      2.86; 95% CI, 1.14-7.18; p=.026). CONCLUSIONS: This retrospective analysis of a
      nationally representative database identified older age, longer anesthesia time,
      and spinal trauma as risk factors for increased incidence of postoperative PE.
      Surgeons should be aware of the increased risk of postoperative PE in these
      subgroups of patients.

PMID- 23158968
TI  - Determination of minimum clinically important difference (MCID) in pain,
      disability, and quality of life after revision fusion for symptomatic
      pseudoarthrosis.
AB  - BACKGROUND CONTEXT: Spinal surgical outcome studies rely on patient reported
      outcome (PRO) measurements to assess the effect of treatment. A shortcoming of
      these questionnaires is that the extent of improvement in their numerical scores
      lacks a direct clinical meaning. As a result, the concept of minimum clinically
      important difference (MCID) has been used to measure the critical threshold
      needed to achieve clinically relevant treatment effectiveness. Post hoc anchor
      based MCID methods have not been applied to the surgical treatment for
      pseudoarthrosis. PURPOSE: To determine the most appropriate MCID values for
      visual analog scale (VAS), Oswestry Disability Index (ODI), Short Form (SF)-12
      physical component score (PCS), and European Quality of Life 5-Dimensions (EQ-5D)
      in patients undergoing revision lumbar arthrodesis for symptomatic
      pseudoarthrosis. STUDY DESIGN/ SETTING: Retrospective cohort study. METHODS: In
      47 patients undergoing revision fusion for pseudoarthrosis-associated back pain,
      PRO measures of back pain (BP-VAS), ODI, physical quality of life (SF-12 PCS),
      and general health utility (EQ-5D) were assessed preoperatively and 2 years
      postoperatively. Four subjective post hoc anchor-based MCID calculation methods
      were used to calculate MCID (average change; minimum detectable change; change
      difference; and receiver operating characteristic curve analysis) for two
      separate anchors (health transition index (HTI) of SF-36 and satisfaction index).
      RESULTS: All patients were available for a 2-year PRO assessment. Two years after
      surgery, a significant improvement was observed for all PROs; Mean change score:
      BP-VAS (2.3+/-2.6; p<.001), ODI (8.6%+/-13.2%; p<.001), SF-12 PCS (4.0+/-6.1;
      p=.01), and EQ-5D (0.18+/-0.19; p<.001). The four MCID calculation methods
      generated a wide range of MCID values for each of the PROs (BP-VAS: 2.0-3.2; ODI:
      4.0%-16.6%; SF-12 PCS: 3.2-6.1; and EQ-5D: 0.14-0.24). There was no difference in
      response between anchors for any patient, suggesting that HTI and satisfaction
      anchors are equivalent in this patient population. The wide variations in
      calculated MCID values between methods precluded any ability to reliably
      determine what the true value is for meaningful change in this disease state.
      CONCLUSIONS: Using subjective post hoc anchor-based methods of MCID calculation,
      MCID after revision fusion for pseudoarthrosis varies by as much as 400% per PRO
      based on the calculation technique. MCID was suggested to be as low as 2 points
      for ODI and 3 points for SF-12. These wide variations and low values of MCID
      question the face validity of such calculation techniques, especially when
      applied to heterogeneous disease and patient groups with a multitude of
      psychosocial confounders such as failed back syndromes. The variability of MCID
      thresholds observed in our study of patients undergoing revision lumbar fusion
      for pseudoarthrosis raises further questions to whether ante hoc or Delphi
      methods may be a more valid and consistent technique to define clinically
      meaningful, patient-centered changes in PRO measurements.

PMID- 23158969
TI  - Radiological analysis of lumbar degenerative kyphosis in relation to pelvic
      incidence.
AB  - BACKGROUND CONTEXT: Lumbar degenerative kyphosis (LDK) is characterized by
      sagittal imbalance resulting from a loss of lumbar lordosis (LL). The pelvic
      incidence (PI) regulates the sagittal alignment of the spine and pelvis. PURPOSE:
      The purpose of this study is to evaluate the spinopelvic parameters in patients
      with LDK and to compare them with those of a normal population. STUDY
      DESIGN/SETTING: A cross-sectional study. PATIENT SAMPLE: The selected patients
      showed characteristic clinical features of LDK. As control group, asymptomatic
      volunteers without spinal pathology were recruited. OUTCOME MEASURES: Full-length
      radiographs of the spine in the anteroposterior and lateral planes were taken,
      extending from the base of the skull to the proximal femur. Pelvic incidence,
      sacral slope (SS), pelvic tilt (PT), main thoracic kyphosis (TK), thoracolumbar
      junction (TLJ), LL, and sagittal vertical axis (SVA) were evaluated. METHODS: In
      terms of PI, the patient and control groups were divided into three groups: low
      (PI<=45 degrees ), middle (45 degrees <PI<=60 degrees ), and high PI groups
      (PI>60 degrees ). All the spinopelvic parameters were compared between each group
      and between the patient and control groups in each group. The correlations
      between each of the parameters were analyzed. RESULTS: We evaluated 172 patients
      with symptomatic LDK and 39 healthy volunteers. The number of LDK patients with
      low, middle, and high PI groups were 44 (25.6%), 72 (44.8%), and 51 (29.6%),
      respectively. In the control group, the number of low, average, and high PI
      patients were 18 (46.2%), 15 (38.5%), and 6 (15.4%), respectively. In the control
      group, PI determined all spinopelvic parameters except SVA. In the LDK group, PI
      also determined spinopelvic parameters except for TK and SVA. Lumbar degenerative
      kyphosis with low PI was associated with pronounced kyphosis in LL and TLJ; LDK
      with a high PI was associated with relatively preserved lordosis in LL with a
      flat or lordotic TLJ. In terms of pelvic parameters, low PI showed flattened SS
      and low PT, whereas high PI showed steep SS and high PT. CONCLUSIONS: The results
      of this study suggest the importance of the key anatomical parameter, PI, in the
      determination of sagittal contour in symptomatic LDK patients and normal
      population. Spinopelvic parameters and pelvic compensatory mechanisms in LDK
      patients differ according to PI. Identifying the spinopelvic parameters is useful
      when correcting deformities.

PMID- 23158970
TI  - Intraosseous ganglion cyst within the L4 lamina causing spinal stenosis.
AB  - BACKGROUND CONTEXT: There are rare reports of intraosseous ganglion cysts in the
      cervical spine. However, to our knowledge, there are no previous reports of these
      cysts occurring in the lumbar spine. PURPOSE: To report a case of symptomatic
      lumbar spinal stenosis caused by an intraosseous ganglion cyst of the L4 lamina
      that communicated with the spinal canal. STUDY DESIGN: Case report. METHODS: An
      86-year-old woman was referred to our spine service for a 2-year history of
      anterior thigh and leg pain. Magnetic resonance imaging revealed a benign
      appearing intraosseous cyst in the left L4 lamina communicating with a posterior
      epidural cyst at L4-L5 causing marked spinal stenosis. The patient was treated
      successfully with a laminectomy and resection. RESULTS: The patient underwent
      partial laminectomies of L4 and L5 preserving the interspinous ligaments between
      L5-S1 and L3-L4. The cyst was removed en bloc without violation of the cyst wall.
      Histopathologic examination revealed focal myxoid changes without a cellular
      lining of the cyst wall, confirming the diagnosis of intraosseous ganglion cyst.
      CONCLUSIONS: This is the first report to describe an intraosseous ganglion cyst
      occurring in the lumbar spine. Although spinal stenosis is commonly a result of
      degenerative joint or disc disease, it occasionally may result from more obscure
      causes. This case illustrates a patient with an intraosseous ganglion cyst within
      the spinal lamina resulting in spinal stenosis, treated successfully with a
      laminectomy and resection.

PMID- 23158971
TI  - Association between circulating ascorbic acid, alpha-tocopherol, 25
      hydroxyvitamin D, and plasma cytokine concentrations in young adults: a cross
      sectional study.
AB  - BACKGROUND: Inflammation and oxidative stress are associated with the
      development of numerous chronic diseases. Circulating ascorbic acid, alpha
      tocopherol, and 25-hydroxyvitamin D (25(OH)D) may help reduce concentrations of
      pro-inflammatory cytokines through their antioxidant and anti-inflammatory
      properties. These micronutrients may act synergistically, and they may have
      different anti-inflammatory effects, but previous studies have assessed the link
      between each of these micronutrients and inflammation in isolation without
      controlling for the other micronutrients. Our objective was to examine the
      association between circulating concentrations of ascorbic acid, alpha
      tocopherol, and 25(OH) D and a panel of pro-inflammatory cytokines in an
      ethnically diverse population of young adults. METHODS: Participants (n = 1,007)
      from the Toronto Nutrigenomics and Health study provided fasting blood samples
      for biomarker measurements and were subsequently categorized into tertiles for
      each micronutrient based on their circulating concentrations. We conducted
      Pearson's correlation analyses across all micronutrients and cytokines. The
      associations between individual micronutrients and cytokines were examined using
      analysis of covariance with age, sex, waist circumference, ethnicity, physical
      activity, season of blood collection, total cholesterol, hormonal contraceptive
      use among women, and the other two micronutrients as covariates. RESULTS: We
      observed weak micronutrient-cytokine correlations, moderate correlations between
      certain cytokines, and strong correlations between specific cytokines,
      particularly interleukin 1- receptor antagonist (IL-1RA), interferon-gamma (IFN
      gamma), and platelet-derived growth factor BB (PDGF-bb). After full covariate
      adjustment, circulating alpha-tocopherol was inversely associated with IFN-gamma
      and regulated upon activation normal T-cell expressed and secreted (RANTES). We
      observed an unexpected positive association between ascorbic acid and IFN-gamma.
      25(OH)D was not associated with altered concentrations of any inflammatory
      biomarkers. CONCLUSIONS: These findings suggest that alpha-tocopherol, but not
      ascorbic acid or 25(OH)D, is inversely associated with inflammation in healthy
      young adults.

PMID- 23158972
TI  - Impulsivity is related to striatal dopamine transporter availability in healthy
      males.
AB  - Impulsivity characterises various psychiatric disorders, particularly attention
      deficit/hyperactivity disorder (ADHD). Evidence shows that ADHD symptoms are
      associated with dopamine dysfunction and alleviated with methylphenidate, a drug
      that reduces dopamine transporter availability. ADHD-like symptoms and impulsive
      traits are continuously distributed across the general population. Here, we aimed
      to investigate the dopaminergic basis of impulsivity and other ADHD-related
      traits in healthy individuals by studying the association of these traits with
      striatal dopamine transporter availability. Single-photon emission computed
      tomography with [(123)I] FP-CIT was performed on 38 healthy males. Impulsivity
      was measured using the Barratt Impulsiveness Scale (BIS) and hyperactivity
      impulsivity and inattention using the Adult ADHD Self-Report Scale (ASRS). We
      found that greater dopamine transporter availability was associated with higher
      BIS impulsivity but not with ADHD-related traits. The association with BIS was
      significant after accounting for individual differences in age and neuroticism.
      These results suggest that individual differences in the dopamine system may be a
      neural correlate of trait impulsivity in healthy individuals.

PMID- 23158973
TI  - Evaluation of agreement between clinical and histopathological data for
      classifying leprosy.
AB  - BACKGROUND: The diversity of clinical manifestations of leprosy has given rise to
      different classification systems. However, there are important differences in the
      sensitivity and specificity of these classifications. The objective of this study
      was to evaluate the agreement between clinical and histopathological data for
      classifying leprosy. METHODS: A total of 1265 patient reports containing clinical
      and histopathological data relating to the diagnosis and classification of
      leprosy were included in this study. The diagnostic concordance between the
      clinical form (Madrid classification) and the histopathological type, as well as
      the initial and final classifications, was calculated by dividing the number of
      concordant cases by the total number of patients. RESULTS: The overall agreement
      between the World Health Organization operational classification and the results
      of direct smear examination of the lesion for acid-fast bacilli was 84.8%
      (1073/1265). The clinical-histopathological agreement was 58.1% (735/1265). The
      indeterminate and lepromatous forms were those that showed the highest
      percentages of agreement: 72.1% (186/258) and 71.0% (142/200), respectively.
      CONCLUSION: Although classifications based on clinical characteristics have an
      important role in the control of leprosy, they present flaws that can influence
      the adequacy of treatment. Therefore, a histopathological examination is
      important for appropriate treatment.

PMID- 23158974
TI  - Laparoscopic ileal interposition with diverted sleeve gastrectomy for treatment
      of type 2 diabetes.
AB  - OBJECTIVE: The objective of the present study was to prospectively evaluate the
      results of laparoscopic ileal interposition (II) with diverted sleeve gastrectomy
      (DSG) for control of T2DM and related metabolic abnormalities. METHODS: All
      patients underwent II +DSG. They had T2DM>=5 years with poor glycemic control
      despite adequate dosage of oral hypoglycemic agents (OHAs) and/or insulin. The
      primary outcome was remission of diabetes (HbA1C<6.5% without OHAs/insulin), and
      secondary outcomes were reduction in antidiabetic agent requirement and
      components of metabolic syndrome. RESULTS: We report the preliminary
      postoperative follow-up data of 9.1+/-5.3 months (range: 3-21 months). There were
      17 patients (male:female=12:5) with mean age of 50.7+/-8.1 (range, 34-66 years),
      duration of diabetes of 15.1+/-5.8 years (range, 5-30 years), and preoperative
      body mass index of 29.2+/-7.5 kg/m(2)(range, 22.4-37.5 kg/m(2)). Eight patients
      (45%) had hypertension, while dyslipidemia and microalbuminuria was present in 7
      patients (39%) each. Twelve patients (70.5%) had diabetes remission. Seven/eight
      (87.5%) patients had remission in hypertension. All participants had weight loss
      ranging between 15% and 30%. Postoperatively statistically significant decline
      was observed in the glycemic and lipid parameters, microalbuminuria at all
      intervals (p<0.05). Two patients had vitamin B12 deficiency 1 year after surgery.
      CONCLUSION: Ileal interposition combined with DSG addresses both foregut and
      hindgut theories and brings about remissions in T2DM patients with reasonable
      safety. Our preliminary observations demonstrated the feasibility and efficacy of
      this novel surgical procedure as a promising option in T2DM.

PMID- 23158975
TI  - Evaluation of nitric oxide metabolites in a group of subjects with metabolic
      syndrome.
AB  - AIM: To evaluate the concentration of metabolites (NO(2)(-), NO(3)(-)) of nitric
      oxide (NO) in metabolic syndrome (MS). MATERIALS AND METHODS: We enrolled 106
      subjects (45 women and 61 men) with MS of which 43 (14 women and 27 men) with
      diabetes mellitus and 63 (31 women and 32 men) without diabetes mellitus, and 54
      subjects (19 women and 35 men) as control group. The nitric oxide metabolites
      (nitrite+nitrate=NOx) were evaluated employing the Griess reagent. RESULTS: In
      the whole group of MS subjects was evident, in comparison with control group, a
      significant increase in NOx. The same finding was also present between control
      group and diabetic subjects with MS and between control group and nondiabetic
      subjects with MS. No difference was observed between the two subgroups (diabetic
      and nondiabetic subjects with MS) about NOx. Contrasting information were
      obtained examining the linear regression among NOx, age, anthropometric profile,
      blood pressure values and glycometabolic pattern of subjects with MS.
      CONCLUSIONS: In MS subjects we found a significant increase in NOx not influenced
      by diabetes mellitus. The NOx is a parameter that must be considered in MS
      keeping in mind that its behavior is related to chronic inflammation that
      accompanies this clinical condition.

PMID- 23158976
TI  - Comparison of glycated hemoglobin with fasting plasma glucose in definition of
      glycemic component of the metabolic syndrome in an Iranian population.
AB  - AIMS: The aim of this study was to compare the utility of glycated hemoglobin
      (GHb) versus the fasting plasma glucose (FPG) in definition of glycemic component
      of the metabolic syndrome (MetS) in a non-diabetic Iranian population. METHODS: A
      cross-sectional study of first-degree relatives (FDRs) of patients with type 2
      diabetes was conducted from 2003 to 2005. A total of 2410 non-diabetic FDRs of
      consecutive patients with type 2 diabetes 30-60 years old were examined. All
      subjects underwent a standard 75 g 2-h oral glucose tolerance test and GHb
      measurement. Consensus criteria in 2009 were used to identify MetS. Glycemic
      component of MetS was defined as either FPG>=100 mg/dl or GHb>=5.7%. The mean
      (SD) age of participants was 43.6 (6.5) years. RESULTS: The prevalence of MetS
      was 33.5% (95% confidence interval (CI): 31.6, 35.4) based on FPG criterion alone
      and 28.6% (95% CI: 26.8, 30.4) based on GHb criterion alone. Use of combination
      of both criteria increased the prevalence of MetS (36.7%; 95% CI: 34.8, 38.6).
      There was 88.7% (95% CI: 87.5, 90.0) agreement between the GHb and FPG when
      either was used to define MetS (kappa coefficient=0.737). CONCLUSIONS: These data
      indicate that using GHb may be an acceptable surrogate of FPG to define glycemic
      component of MetS.

PMID- 23158977
TI  - Accumulation of plasma 3-deoxyglucosone impaired glucose regulation in Chinese
      seniors: implication for senile diabetes?
AB  - AIMS: To investigate the impact of increasing accumulation of 3-deoxyglucosone (3
      DG) on glucose regulation in non-diabeteic seniors. METHODS: This research is a 2
      year prospective follow-up study. We conducted a HPLC assay to determine the
      plasma 3-DG concentrations of 132 non-diabetic retirees of Suzhou. An oral
      glucose tolerance test was carried out 2 years after baseline in 16 subjects with
      continual high plasma 3-DG and 16 control subjects randomly sampled in those with
      normal plasma 3-DG. RESULTS: The median plasma 3-DG level of 132 subjects was
      43.52 ng/ml (7.89-736.09 ng/ml), of which 47 subjects (36.6%) were beyond 70
      ng/ml. A correlation between age and 3-DG was found among people between 50 and
      66 years old (r=0.408, P<0.001). The 60-69 years group had a higher 3-DG level
      than 50-59 years group (P<0.001). Compared with control group, the continual high
      plasma 3-DG subjects had a higher level of FINs (P<0.05), FBG (P<0.01), HOMA-IR
      (P<0.001), and a lower level of ISI (P<0.001) and DeltaI(60)/DeltaG(60) (P<0.05),
      as well as a higher incidence of impaired glucose regulation (chi(2)=7.814,
      P<0.05). CONCLUSIONS: There was abnormal elevation of plasma 3-DG in non-diabetic
      seniors, and the increasing accumulation of plasma 3-DG, which mainly resulted
      from aging, eventually lead to the impaired glucose regulation, indicating an
      association of 3-DG with senile diabetes.

PMID- 23158978
TI  - Vitamin D as a predictor of insulin resistance in polycystic ovarian syndrome.
AB  - INTRODUCTION: Polycystic Ovary Syndrome (PCOS) is the most common
      endocrinological disorder in women in the reproductive age group. The salient
      features of this condition include hyperandrogenic features, infertility and
      insulin resistance among others. Mechanisms behind these features are a matter of
      debate. Vitamin D has been implicated lately in the etiology of many disorders.
      The aim of our study was to assess the role of vitamin D as an etiological and
      predictive factor in PCOS. MATERIALS AND METHODS: The study comprised 60 proven
      cases of PCOS diagnosed on the basis of Rotterdam criteria. The parameters
      assessed include HOMA-IR, vitamin D besides the routine anthropometric and
      biochemical parameters. RESULTS: The study population was divided into 3 groups
      according to vitamin D status. Insulin resistance was most severe in the sub
      group with vitamin D deficiency. Multiple regression analysis established the
      role of vitamin D as the best predictor of insulin resistance in our study.
      CONCLUSION: Vitamin D has an important role in the pathogenesis of insulin
      resistance in PCOS.

PMID- 23158979
TI  - The heteroplasmic 15059G>A mutation in the mitochondrial cytochrome b gene and
      essential hypertension in type 2 diabetes.
AB  - AIM: The long-term stress of high blood pressure levels increases the risk of a
      variety of macro- and microvascular complications of type 2 diabetes (T2D). The
      etiology of essential hypertension (EH) has been explored in depth, but the
      pathophysiology is multifactorial, complex, and poorly understood. Recent
      findings showed a role of inherited mutations in mitochondrial DNA (mtDNA) in
      maternally inherited forms of hypertension. However, an impact of somatic mtDNA
      mutations in the development of EH is significantly less investigated. In this
      study, we examined whether the level of heteroplasmy for the 15059G>A mutation in
      the mitochondrial cytochrome b gene is associated with EH in T2D. PATIENTS AND
      METHODS: The heteroplasmy level in mtDNA isolated from blood of 189 diabetic
      participants randomly selected from general population (124 of whom had EH) was
      quantified using a real-time PCR. RESULTS: The 15059G>A heteroplasmy exceeding
      39% was found to be significantly associated with a higher risk of EH (odds ratio
      1.96; P (Fisher) 0.032). CONCLUSION: There is the first evidence reporting
      association between the mtDNA 15059G>A mutation heteroplasmy and EH in T2D.

PMID- 23158980
TI  - Use of HbA(1C) testing to diagnose pre-diabetes in high risk African American
      children: a comparison with fasting glucose and HOMA-IR.
AB  - OBJECTIVE: This study aimed to compare the discriminating power of HbA(1C) with
      other pre-diabetes diagnostic tests specifically in high-risk African American
      children. RESEARCH DESIGN AND METHODS: A cross-sectional analysis was performed
      on a sample of 172 children (70 boys and 102 girls) aged 9-11 years with BMI's
      above the 85th percentile. Fasting glucose, insulin and HbA(1C) were analyzed
      from the plasma samples. RESULTS: Of the 172 participants included in this
      analysis, 21 (12.2%) had HbA(1C) concentrations above the cutoff of 5.7 used to
      identify pre-diabetes. None (0%) of these 21 participants, however, were observed
      to have a glucose concentration above the pre-diabetes cutoff of 110 mg/dl, and
      only 13 of 21 participants had HOMA-IR above the pre-diabetes cutoff of 2.5. When
      compared to the previously identified glucose cutoff of 110 mg/dl and HOMA-IR
      cutoff of 2.5 for pre-diabetes, HbA(1C) showed high specificity (88 and 93%,
      respectively) but very low sensitivity (0 and 21%, respectively). Glucose,
      insulin and HOMA-IR were significantly interrelated, but HbA(1C) was not
      significantly correlated with these biochemical prediabetes assessment variables,
      nor with anthropometric (BMIz, WC) risk factors. CONCLUSION: Our results suggest
      that HbA(1C) had poor discrimination power to identify prediabetes in overweight
      and obese 9- to 11-year-old African American children. Future studies are
      recommended to compare the feasibility, sensitivity and predictive power of
      different screening tests currently recommended to avoid inadequacy when
      screening for prediabetes and diabetes.

PMID- 23158981
TI  - Role of surrogate markers in assessment of insulin resistance in females with
      thyroid disorders.
AB  - INTRODUCTION: Thyroid status is known to affect insulin sensitivity although
      conflicting data have been reported regarding hypothyroid and hyperthyroid
      states. Assessment of insulin resistance is difficult, therefore we compared
      homeostasis model assessment (HOMA), glucose to insulin (G:I) ratio, glucose to C
      peptide (G:C) ratio and ferritin of hypothyroid and hyperthyroid subjects with
      euthyroid, euglycemic subjects. METHODS: The study group comprised of 40
      hypothyroid, 25 hyperthyroid female subjects and 40 euthyroid controls. Serum
      samples of all the patients were assayed for thyroid profile, glucose, Insulin, C
      peptide and ferritin. Homeostasis model of assessment (HOMA-IR), (G:I), (G:C) and
      ferritin were employed as surrogate measures to assess the level of insulin
      resistance. The area under the curves for the surrogate markers was determined
      from the receiver operating characteristics (ROC) curves for the hypothyroid and
      hyperthyroid patients. RESULTS: Patients with hypothyroidism demonstrated insulin
      resistance as observed by the higher HOMA-IR and G:I ratio as compared to the
      controls whereas insulin resistance was not detected in the hyperthyroid patients
      in our study. CONCLUSION: Thyroid dysfunction attributes to deranged glucose
      metabolism. Assessment of the surrogate markers might prove to be beneficial in
      detecting insulin resistance at the incipient stages and subsequent management.

PMID- 23158982
TI  - Explorative study on diabetes neuropathy among type II diabetic patients in
      Universiti Sains Malaysia Hospital.
AB  - OBJECTIVE: The aim of this study was to determine risk factors and prevalence of
      diabetic neuropathy (DN) among type II diabetic patients in Malaysian hospital
      setting. SUBJECTS AND METHODS: a observational prospective longitudinal follow up
      study design was selected, total no of respondents were 1077 type 2 diabetes
      mellitus outpatients recruited via attended the diabetes clinics at Hospital
      Universiti Sains Malaysia (HUSM) in Kelantan. The diagnosis of neuropathy was
      confirmed by nerve conduction studies. Logistic regression analysis was used to
      assess the independent variables that affect the development of neuropathy.
      RESULTS: The prevalence of nephropathy is 54.3%. Longitudinal logistic regression
      identified four predictive variables on the development and progression of
      diabetic neuropathy that are: duration of diabetes, retinopathy, HbA1c at second
      visit, and creatinine clearance third visit. CONCLUSION: Findings of this study
      show high prevalence of diabetic neuropathy. HbA1c and creatinine clearance are
      two modifiable risk factors for the development of diabetic neuropathy.

PMID- 23158983
TI  - Efficacy and safety of statin and fibrate combination therapy in lipid
      management.
AB  - Adequate control of hyperlipidemia is of paramount importance for prevention of
      vascular events. Statins and fibrates are well established treatments for
      hyperlipidemia. Combination therapy with a statin and fibrate offers significant
      therapeutic advantage for the treatment of severe or refractory mixed
      hyperlipidemia. Although such a combination does increase the risk of myopathy,
      with an incidence of approximately 0.12%, this small risk of myopathy rarely
      outweighs the established morbidity and mortality benefits of achieving lipid
      goals. Nevertheless, a higher incidence of myopathy has been reported with statin
      monotherapy. Statin+fibrate therapy should be considered if monotherapy or adding
      other drugs (e.g. cholesterol absorption inhibitors, omega-3 fatty acids or
      nicotinic acid) did not achieve lipid targets or is impractical. The current
      article focuses on recent studies highlighting the beneficial effects of this
      combination.

PMID- 23158984
TI  - Obesity, hypothyrodism and hypermanganesemia: a case report.

PMID- 23158985
TI  - Continuous positive airway pressure and type 2 diabetes mellitus.
AB  - Obstructive sleep apnea (OSA) is a sleep disorder, increasingly recognized. It is
      commonly present in obese persons, treated with continuous positive airway
      pressure (CPAP), being the gold standard. The disorder has been associated with
      diabetes mellitus and possibly related to hypoxia per se, increased sympathetic
      activity, disturbed hypothalamic-pituitary-adrenal axis and increased
      inflammatory cytokines and leptin, all of which can adversely affect both glucose
      metabolism and insulin sensitivity. Given this association and the presence of
      common risk factors, this review assessed the impact of CPAP on diabetes mellitus
      through various metabolic parameters including HbA1c, nocturnal glucose and
      insulin resistance, in addition to the effect of CPAP on the prevention of
      diabetes mellitus. Results have been conflicting; Randomized controlled trials
      are recommended to allow objective and definite conclusions.

PMID- 23158986
TI  - [Research on recombinant human PA2G4 family member Ebp1: current status and
      future perspective].

PMID- 23158987
TI  - [Effect of HMGB1 on the VEGF-C expression and proliferation of esophageal
      squamous cancer cells].
AB  - OBJECTIVE: To explore the effect of HMGB1 on the VEGF-C expression and
      proliferation of esophageal squamous cancer cells as well as its possible
      mechanism. METHODS: A cassette encoding siRNA targeting HMGB1 mediated by rAAV
      was constructed, the rAAV-siHMGB1-hrGFP, and a vector encoding siRNA mismatching
      HMGB1 was constructed, the rAAV-miHMGB1-hrGFP. This experiment in vitro included
      three groups, namely, the blank control group (group A) of KYSE150 cells
      transfected by rAAV-hrGFP, negative mismatch control group (group B) of KYSE150
      cells transfected with rAAV-miHMGB1-hrGFP, and RNA interference group (group C)
      of KYSE150 cells transfected with rAAV-siHMGB1-hrGFP. We examined the expression
      of HMGB1 mRNA and protein in the three group cells by real-time PCR and Western
      blot after 24 h and 48 h, respectively. Then, VEGF-C expression and cell
      proliferation in the three group cells with or without sRAGE, as an inhibitor of
      RAGE signal pathway, were assayed by ELISA and MTT after 24 h. RESULTS: The
      expression of HMGB1 mRNA and protein in KYSE150 cells in vitro in the group C
      transfected with rAAV-siHMGB1-hrGFP at the final concentration of 2*10(6)
      v.g/cell was significantly lower than that of the group A or B after 24 h and 48
      h (P < 0.01). The VEGF-C expression of KYSE150 cells was (502.43 +/- 13.10) pg/ml
      in the group C, significantly reduced in comparison with that of the group A
      (686.40 +/- 10.94) pg/ml or group B (682.31 +/- 9.61) pg/ml after 24 h (P <
      0.05). At the same time, the proliferation of KYSE150 cells in the group C was
      significantly inhibited compared with that of groups A and B after 24 h (P <
      0.01). Moreover, sRAGE at the final concentration of 0.2 ug/ml inhibited the VEGF
      C expression and proliferation of KYSE150 cells compared with the corresponding
      group without sRAGE after 24 h (P < 0.01 or P < 0.05). However, there was no
      significant difference of the VEGF-C expression and proliferation of KYSE150
      cells with sRAGE in the group C compared with that of cells with sRAGE of the
      group A or group B after 24 h (P > 0.05). CONCLUSIONS: In esophageal squamous
      cell carcinoma, HMGB1 can promote the VEGF-C expression and proliferation of the
      cancer cells through RAGE signal pathway, and HMGB1-RAGE may become a potential
      target for cell proliferation and lymph node metastasis of this cancer.

PMID- 23158988
TI  - [Preliminary analysis of differentially expressed proteins of clear-cell renal
      cell carcinoma by comparative proteomic technologies].
AB  - OBJECTIVE: To explore the different expression of proteins between human clear
      cell renal cell carcinoma (ccRCC) cell line RLC-310 and normal renal proximal
      tubule epithelial cell line HK-2, and to search new differentially expressed
      proteins of RCC. METHODS: RLC-310 and HK-2 cells were cultured in vitro. The
      total proteins were separated by ProteomeLab PF 2D protein fractionation system
      and the differential expression protein fractions of the two cell lines were
      analyzed and identified by capillary liquid chromatography-electrospray
      ionization-mass spectrometry (LC-ESI-MS/MS). RT-PCR and Western blot were used to
      confirm the representative differential expression at mRNA and protein levels.
      RESULTS: One hundred and ninty-six differentially expressed proteins were
      identified. These differentially expressed proteins involved in many aspects,
      including cell proliferation and anti-apoptosis, energy metabolism, mitochondria
      reduction and oxidation, oxidative stress and resistance, cell signaling,
      invasion and adhesion, cytoskeleton and motion, neovascularization, etc. Except
      for previously reported RCC associated proteins: annexin A2, fatty acid-binding
      protein, vimentin, fibronectin, and so on, Septin-9 was firstly found highly
      expressed in RLC-310 cells when compared with that in the HK-2 cells. Moreover,
      the overexpression of Septin-9 was confirmed by RT-PCR and Western blot analysis
      at both mRNA and protein levels (P < 0.05). CONCLUSIONS: The human ccRCC cell
      line RLC-310 cells display differential protein profiles compared with those of
      the normal renal cell line HK-2 cells. The identified differential expression
      proteins are involved in many aspects of RCC development. It is worth further
      study and elucidate the molecular mechanisms of RCC. The representative
      differential protein Septin-9 deserves further study its role in the angiogenesis
      of ccRCC.

PMID- 23158989
TI  - [Essential role of TRPC6 in the proliferation of gastric cancer and its
      mechanism].
AB  - OBJECTIVE: To investigate the essential role and mechanism of TRPC6 gene in the
      development of gastric cancer. METHODS: The expression of TRPC6 protein was
      assessed in gastric cancer tissues and normal tissues adjacent to the cancer from
      30 patients with gastric cancer. The inhibiting effect of TRPC6 activity on cell
      growth, cell cycle of a human gastric cancer cell line AGS cells, tumor
      progression and development of xenografted human gastric cancer in a mouse model
      was tested using dominant-negative mutant TRPC6 (DNC6). The survival of mice
      bearing xenografted tumors in the GFP and DNC6 was compared using Kaplan-Meier
      analysis. All statistical tests were two-sided. RESULTS: The TRPC6 protein in the
      tumor tissues and para-tumor tissues was (21.60 +/- 8.32)% versus (7.14 +/-
      2.24)%. After transfection of DNC6 virus for 24 hours, 48 hours, 72 hours and 96
      hours, the growth inhibition rates of gastric cancer cells were (36.90 +/-
      1.13)%, (44.06 +/- 2.17)%, (52.12 +/- 2.76)% and (50.89 +/- 1.97)%, respectively.
      The clone formation rates of control group and DNC6 group were (14.70 +/- 3.00)%
      versus (43.80 +/- 7.00)%. After transfection with DNC6 virus for 0, 24, 36 and 48
      hours, the G(2)/M phase arrest was (20.34 +/- 1.98)%, (24.31 +/- 2.37)%, (27.70
      +/- 2.36)%, (35.10 +/- 3.0)% in the DNC6 group and (18.40 +/- 2.01)%, (18.0% +/-
      1.72)%, (17.50 +/- 1.74)%, (16.80 +/- 1.71)% in the control group, respectively.
      Inhibition of TRPC6 activity also reduced the subcutaneous tumor volume in the
      mouse models with xenografted human tumors (P < 0.05). CONCLUSION: In the
      preclinical models tested, TRPC6 channels are essential for gastric cancer
      development via regulation of G(2)/M phase transition.

PMID- 23158990
TI  - [10-year changes and development of surgical treatment for breast cancer in
      China].
AB  - OBJECTIVE: To investigate the changes and development of surgical treatment for
      breast cancer from 1999 to 2008 in China, and compare the differences between the
      surgical methods used in high-resource and low-resource areas. METHODS:
      Clinicopathological data of surgical treatment for female primary breast cancer
      was collected via medical chart review at hospitals in seven geographic areas in
      China. Chi-square test and chisqure test for linear trends were used to analyze
      the changes and development of the surgical methods used for breast cancer in the
      10 years. RESULTS: A total of 4211 primary breast cancer patients were selected
      from the 10-year database, including 4078 women (97.5%) treated by surgical
      operation. Among 3271 women (80.21%) treated with modified radical mastectomy,
      the surgical rate was rising from 68.89% in 1999 to 80.17% in 2008, ascending by
      11.28% (chi(2) = 31.143, P < 0.001). In high-resource areas, the surgical rate of
      modified radical mastectomy was rising from 45.64% in 1999 to 76.13% in 2008,
      ascending by 30.49% (chi(2) = 89.393, P < 0.001), while in low-resource areas it
      kept a steady rate at 80% in the ten years (chi(2) = 2.113,P = 0.146). Among 231
      women (5.66%) treated with breast-conserving surgery, the surgical rate was
      rising from 1.29% in 1999 to 11.57% in 2008, ascending by 10.28% (chi(2) =
      102.835, P < 0.001). In high-resource areas, the surgical rate of breast
      conserving surgery was rising from 2.68% in 1999 to 16.87% in 2008, ascending by
      14.19% (chi(2) = 69.544, P < 0.001), while in low-resource areas it was rising
      from 0.42% in 1999 to 6.22% in 2008, ascending by 5.80% (chi(2) = 30.003, P <
      0.001). Among 469 women (11.50%) treated with Halsted radical mastectomy, the
      surgical rate was declining from 28.28% in 1999 to 4.96% in 2008, descending by
      23.32% (chi(2) = 206.202, P < 0.001). In high-resource areas, the surgical rate
      of Halsted radical mastectomy was declining from 50.34% in 1999 to 3.29% in 2008,
      descending by 47.05% (chi(2) = 274.830, P < 0.001), while in low-resource areas
      it was declining from 14.58% in 1999 to 6.64% in 2008, descending by 7.94%
      (chi(2) = 8.166, P = 0.004). Among 3786 women treated with breast mastectomy
      (including modified radical mastectomy and Halsted radical mastectomy), the
      surgical rate was declining from 98.46% in 1999 to 86.36% in 2008, descending by
      12.10% (chi(2) = 95.744, P < 0.001). In high-resource areas, the surgical rate of
      breast mastectomy was declining from 96.64% in 1999 to 80.66% in 2008, descending
      by 15.98% (chi(2) = 53.446, P < 0.001), while in low-resource areas it was
      declining from 99.58% in 1999 to 92.12% in 2008, descending by 7.46% (chi(2) =
      36.758,P < 0.001). CONCLUSIONS: The main primary surgical treatment for breast
      cancer is modified radical mastectomy during the period 1999 - 2008. Halsted
      radical mastectomy is gradually replaced by modified radical mastectomy and
      breast-conserving surgery. The rate of changes for breast-conserving surgery and
      mastectomy is higher in high-resource areas than that in low-resource areas.
      Breast-conserving surgery will become the main treatment for early-stage breast
      cancer.

PMID- 23158991
TI  - [Expression and significance of Twist1 and MMP-2 in endometrial endometrioid
      adenocarcinoma].
AB  - OBJECTIVE: To investigate the expression of Twist1 and MMP-2 protein and their
      significance in endometrial endometrioid adenocarcinoma. METHODS: The expression
      of Twist1 and MMP-2 protein in 70 cases of endometrial endometrioid
      adenocarcinoma was detected on tissue chips using immunohistochemical staining.
      RESULTS: The positive rates of Twist1 and MMP-2 protein expression were 65.7% and
      67.1%, respectively. Both of the high expressions of Twist1 and MMP-2 were
      positively correlated with FIGO staging and tumor myometrial invasion (P < 0.05,
      respectively). Also the high expression of Twist1 was positively correlated with
      ovarian metastasis and the expression of MMP-2 was positively correlated with
      tumor grading (P < 0.05). The patients' overall survival and relapse-free
      survival in the group of high Twist1 expression were shorter than that in the
      group of low Twist1 expression (P < 0.05). The expression of MMP-2 was positively
      correlated with Twist1 expression (P < 0.01, respectively). CONCLUSIONS: The
      expression of Twist1 may be closely correlated with the tumor invasion,
      metastasis and prognosis in patients with endometrial endometrioid
      adenocarcinoma. The expression of Twist1 has a close relationship with MMP-2 in
      endometrial endometrioid adenocarcinoma.

PMID- 23158992
TI  - [Expression of metastasis associated 1 family member 2 (MTA2) in gastric cancer
      and its relationship with transcription factor Sp1].
AB  - OBJECTIVE: To determine the expression patterns of metastasis associated 1 family
      member 2 (MTA2) in gastric cancer and non-cancerous gastric mucosa, and analyze
      its relationship with nuclear transcription factor Sp1 expression. METHODS:
      Tissue samples and clinicopathological information from 83 gastric cancer
      patients, who underwent surgery, were collected from Shanghai Rui Jin Hospital.
      All samples included cancer tissue and non-cancerous mucosa which was 5 cm away
      from the tumor lesion. The expression of MTA2 and Sp1 were detected by
      immunohistochemistry (IHC) staining. The mRNA of MTA2 was also detected by
      reverse transcription-polymerase chain reaction (RT-PCR). SPSS software was used
      for statistical analysis. RESULTS: The expression of MTA2 protein was
      significantly higher in primary lesions of the gastric cancer than that in non
      cancerous mucosa by IHC (31.3% vs 12.0%, P < 0.01). MTA2 expression was closely
      related with tumor invasion or T staging (chi(2) = 5.677, P < 0.05). Yet, no
      significant relationship was observed between MTA2 expression and other
      clinicopathological parameters, including the age, sex, tumor differentiation,
      Lauren classification, lymph node metastasis, distant metastasis, as well as
      pathological staging. Furthermore, MTA2 expression was concomitant with Sp1
      expression (r = 0.320, P < 0.05). Elevated MTA2 expression was observed in Sp1
      positive cancer tissues (chi(2) = 9.565, P < 0.01). RT-PCR results also
      demonstrated that MTA2 mRNA was also highly expressed in the tissue samples with
      Sp1 expression. CONCLUSIONS: MTA2 is highly expressed in the primary lesions of
      gastric cancer than that in adjacent non-cancerous tissues, and is closely
      related with tumor invasion. MTA2 expression is elevated in Sp1 positive gastric
      cancer.

PMID- 23158993
TI  - [Expression of CD4(+) and IL-17, Foxp3 in non-small cell lung cancer and their
      correlation with microvessel density].
AB  - OBJECTIVE: To explore the expression of CD4(+), IL-17 and Foxp3 in non-small cell
      lung cancer (NSCLC) and their relationship with microvessel density (MVD).
      METHODS: The expressions of CD4(+), IL-17, Foxp3, CD31 and CD34 in the cancer
      tissues of 102 NSCLC cases were detected by immunohistochemisty. The relationship
      among the expressions of CD4(+), IL-17, Foxp3 and MVD was analyzed. The count
      data were analyzed using chi(2) test. The measurement data were analyzed using
      single-factor analysis of variance, and significance level alpha = 0.05. RESULTS:
      Among the factors affecting CD31 expression, there was a statistically
      significant difference between the strong positive Foxp3 expression (++) and
      negative (-) and positive expressions (+) in the NSCLC cancer tissues (P < 0.05),
      and between the expressions in stage I and III cancer tissues (P < 0.05). Among
      the factors affecting CD34 expression, there was a significant difference between
      positive IL-7 expression (+) and strong positive IL-7 expression (++) (P < 0.05),
      between negative Foxp3 expression (-) and strong positive Foxp3 expression (++)
      (P < 0.05), and between the CD34 expressions in stage I and III and between those
      in stage II and III NSCLC cancer tissues (P < 0.05). CONCLUSIONS: CD4, IL-17and
      Foxp3 may be involved in the tumor suppression caused by host immune response,
      and are related with the NSCLC invasion and metastasis.

PMID- 23158994
TI  - [Significance of TIMP-1 and nm-23 expressions in HER-2-positive breast cancer].
AB  - OBJECTIVE: Trastuzmab combined therapy has been recommended as standard therapy
      for HER-2-positive breast cancer. However, more than 70% HER-2-positive cases do
      not recur and might thus be with overtreatment risk. The aim of this study was to
      explore the significance of TIMP-1 and nm-23 expression in identifying the good
      prognosis subtype in HER-2-positive breast cancer. METHODS: One hundred and sixty
      five cases of HER-2-positive breast cancer treated in Tianjin Medical University
      Cancer Hospital from Jan. 1987 to Dec. 1988 were studied. Expressions of TIMP-1
      and nm-23 were detected by immunohistochemistry and the correlation with
      clinicopathologic characteristics and long-term outcome was analyzed. RESULTS:
      53.3% (88/165) of TIMP-1 and 72.7% (120/165) of nm-23 expression were detected in
      the patients. The TIMP-1-negative patients classified as good prognosis group had
      a 10-year metastasis free survival (MFS) of 58.4% and 10-year overall survival
      (OS) of 68.8%, compared with the 10-year MFS of 43.2% (P = 0.041) and 10-year OS
      of 52.0% in the positive group (P = 0.020). The nm-23-positive patients
      classified as good prognosis group had a 10-year MFS of 54.2% and 10-year OS of
      65.7%, compared with the 10-year MFS of 40.0% (P = 0.049) and 44.1% (P = 0.015)
      in the negative group. The multivariate analysis showed that expressions of TIMP
      1 and nm-23, tumor size and lymph node involvement were independent prognostic
      factors. CONCLUSIONS: In HER-2-positive breast cancer, TIMP-1 and nm-23 can be
      used to further distinguish between low-risk and high-risk subgroups, and they
      are independent factors in prognosis.

PMID- 23158995
TI  - [Expression of erythropoietin and erythropoietin receptor in non-small cell lung
      cancer and its correlation with microvessel density].
AB  - OBJECTIVE: Erythropoietin and erythropoietin receptor (EPO-R) are expressed in
      many kinds of tumors. The EPO/EPO-R signaling is involved in tumor cell
      proliferation, invasion and angiogenesis. The aim of this study was to detect the
      expression of EPO-R in non-small cell lung cancer (NSCLC), and explore its
      correlation with angiogenesis. METHODS: The expression patterns of EPO and EPO-R
      in 31 cases of NSCLC tissues were detected by immunohistochemistry, and that in
      benign lung lesions of 21 patients as control. To analyze the correlation of
      EPO/EPO-R expression patterns and clinicopathological factors. CD34 was used to
      label the vascular endothelial cells and calculate the microvessel density (MVD).
      RESULTS: The positive rates of EPO and EPO-R expression in NSCLC were 67.7% and
      96.8%, respectively, significantly higher than those in the control ones. The
      positive rates of EPO and EPO-R expression in adjacent tissues were 19.4% and
      35.5%, and in benign lesions were 9.5% and 19.0%, respectively (P < 0.001). The
      expression patterns of EPO/EPO-R were not related with pTNM stage, histological
      type, histological grade and lymph node metastasis (P > 0.05). Increased MVD was
      correlated with poor differentiation, lymph node metastasis, and advanced stage.
      CONCLUSIONS: High expression of EPO/EPO-R in NSCLC patients suggest that they may
      be involved in tumorigenesis. EPO/EPO-R expression and MVD are closely related,
      and they might be an endogenous stimulant of angiogenesis during the progression
      of non-small cell lung cancer. It may provide evidence for clinical diagnosis.

PMID- 23158996
TI  - [Efficacy of European Organization for Research and Treatment of Cancer (EORTC)
      risk tables for the prediction of recurrence and progression of non-muscle
      invasive bladder cancer after intravesical pirarubicin instillation].
AB  - OBJECTIVE: To analyze the influence of intravesical Pirarubicin (THP)
      instillation on the prediction results of European Organization for Research and
      Treatment of Cancer (EORTC) risk tables and to discuss the efficacy of EORTC risk
      tables in clinical application. METHODS: We retrospectively reviewed the clinical
      data of 389 patients with non-muscle invasive bladder cancer after TURBT treated
      with intravesical pirarubicin instillation. According to the EORTC Scoring
      System, all the cases were divided into low risk group, intermediate risk group
      and high risk group. The 1-year and 5-year recurrence and progression rates of
      each group were calculated and compared with the prediction results of the EORTC
      risk tables. RESULTS: The 1-year recurrence and progression rates of the low risk
      group were 8.0% and 0, those of the intermediate risk group were 31.0% and 2.8%,
      and those of the high risk group were 52.5% and 18.6%, respectively. The 5-year
      recurrence and progression rates of low risk group were 16.0% and 5.3%, those of
      the intermediate risk group were 42.6% and 10.7%, and those of the high risk
      group were 63.9% and 41.9%, respectively. The prediction results of progression
      rate were similar to that of the EORTC risk tables while the overall recurrence
      rate was lower. CONCLUSIONS: The EORTC risk tables can be effectively used to
      predict the recurrence rate and progression rate of non-muscle invasive bladder
      cancer. However, the EORTC risk tables have a tendency to overestimate the
      recurrence rate. Intravesical pirarubicin instillation is helpful to reduce the
      recurrence rate, yet has no obvious influence on the tumor progression.

PMID- 23158997
TI  - [Value of endobronchial ultrasound-transbronchial needle aspiration biopsy for
      diagnosis of PET-CT positive mediastinal lymph nodes].
AB  - OBJECTIVE: To evaluate the clinical value of endobronchial ultrasound
      transbronchial needle aspiration (EBUS-TBNA) biopsy for diagnosis of PET-CT
      positive mediastinal lymph nodes. METHODS: One hundred and twenty-six patients
      with lung cancer undergoing both PET-CT scanning and EBUS-TBNA biopsy in the
      First Affiliated Hospital of Guanzhou Medical College from July 2008 to August
      2010 were included in this study. There were 89 male and 37 female patients with
      a mean age of 56.3 years (range 34 to 81 years). (18)FDG-PET was considered
      positive in mediastinal nodes if the PET-CT reported hypermetabolic activity
      consistent with malignant disease (standardized uptake value > 2.5). All of the
      patients were clinically followed up. RESULTS: Among the 126 patients, 185
      stations of lymph nodes were punctured. The mean diameter of the nodes was 13.6
      mm and the range was 6 - 23 mm. There were no procedural complications. The
      diagnostic accuracy, sensitivity, and specificity of EBUS-TBNA were 95.7%, 95.7%,
      and 100%, respectively. CONCLUSIONS: EBUS-TBNA is a minimally invasive, highly
      effective and accurate, practical and safe procedure for diagnosis of PET-CT
      positive mediastinal lymph nodes.

PMID- 23158998
TI  - [Clinicopathological features and prognosis of primary appendiceal
      adenocarcinoma].
AB  - OBJECTIVE: To explore the clinicopathological characteristics and prognostic
      factors of primary appendiceal adenocarcinoma. METHODS: The clinicopathological
      data of 42 patients with primary appendiceal adenocarcinoma treated in the Cancer
      Hospital of Chinese Academy of Medical Sciences between March 1994 and October
      2009 were retrospectively analyzed. The survival analysis was conducted using
      Kaplan-Meier method. The factors influencing survival were analyzed using
      univariate (Log-rank) and multivariate (Cox) models. RESULTS: A total of 42
      patients (29 female and 13 males, median age 56 years) with appendiceal
      adenocarcinoma were included in this study. Of them, 26 (61.9%) were mucinous
      adenocarcinoma, 12 (28.6%) were intestinal-type adenocarcinoma and 4 (9.5%) were
      signet cell carcinoma. 18 patients underwent curative resection, 20 patients
      received cytoreductive surgery, and 4 patients underwent biopsy only. Thirty
      patients received systemic chemotherapy (5-Fu-based regimens). One patient who
      died of postoperative pulmonary embolism on day 8 was excluded from the survival
      analysis. The overall 1-, 3-, and 5-year survival rate was 80.3%, 46.0% and
      38.3%, respectively. Univariate analysis revealed that presence of symptoms of
      acute appendicitis, curative resection, histological grade, histological subtype,
      preoperative CEA level, systematic chemotherapy, and stage were all significant
      factors affecting the survival. Multivariate analysis showed that the
      preoperative CEA level (P = 0.01), histological grade (P = 0.001), and stage (P =
      0.001) were independent prognostic factors. CONCLUSIONS: High level of CEA, G2/3
      grade, and advanced stage are associated with poor prognosis in patients with
      primary appendiceal adenocarcinoma.

PMID- 23158999
TI  - [Clinical features and prognosis of 25 cases of breast carcinosarcoma].
AB  - OBJECTIVE: To improve the recognition, appropriate diagnosis and treatment of
      breast carcinosarcoma through analysis of their clinical features, diagnosis,
      management and prognosis. METHODS: The clinicopathological data from 25 patients
      with breast carcinosarcoma treated in our hospital between January 1976 and
      January 2008 were retrospectively reviewed. The correlation between prognosis and
      age, tumor size, axillary node status, and treatment modality was analyzed using
      the statistical software SPSS 13.0. The survival rate was calculated by Kaplan
      Meier analysis and compared using log-rank test. Univariate and multivariate
      factors for survival were analyzed using Cox proportional hazards regression
      model. RESULTS: All patients were female and their median age was 56-years. The
      median tumor diameter was 5.1 cm. The misdiagnosis rate was high by mammography,
      B-ultrasound and pathological examination of needle aspiration biopsy before
      operation. So that the diagnosis primarily depended on postoperative
      histopathologic examination. The ER/PR and HER-2 positive rate of the breast
      carcinosarcomas was 8.3% and 7.7%, respectively. Invasive ductal carcinoma was
      the main malignant component accounting for 92.3%, while the sarcoma element was
      constitutive of fibrosarcoma with a proportion of 46.2%. The overall 5-year
      survival rate was 57.9% with a median survival time of 86 months after a median
      follow-up of 52 months. Univariate factor analysis showed that the tumor size (P
      = 0.012) and treatment methods (P = 0.028) were impact factors, while age and
      axillary lymph node status were not significantly related with prognosis. Cox
      multivariate analysis validated that the therapy modality was an independent
      prognostic factor for breast carcinosarcoma (P = 0.047). CONCLUSIONS: Breast
      carcinosarcoma is rare and its clinical features are not specific, so that its
      final diagnosis is mainly based on the postoperative pathology. Tumor size and
      treatment modality are independent prognostic factors, so the comprehensive
      therapy mainly based on radical resection is the best treatment modality. The
      positive expression of ER/PR and HER-2 in breast carcinosarcoma is low, while
      exploring new target is one of future research directions.

PMID- 23159000
TI  - [Application of trans-abdominal-mediastinal drainage tube in patients with high
      risk of esophagogastric or esophago-jejunal anastomotic leakage].
AB  - OBJECTIVE: To evaluate the therapeutic effects of trans-abdominal-mediastinal
      drainage tube on the prevention of esophagogastric or esophago-jejunal
      anastomotic leakage. METHODS: A total of 79 patients underwent thoraco-abdominal
      radical resection for gastric cardia cancer, with high risk of leakage of the
      anatsomosis, from Aug. 2007 to Aug. 2011 were included in this study. They were
      assigned into 2 groups. Forty one patients had trans-abdominal-mediastinal
      drainage tube (improvement group) and 38 patients were without the mediastinal
      drainage tube (control group). The clinical data of all the 79 patients were
      reviewed and the therapeutic effects of the two treatment approaches were
      compared. RESULTS: There was anastomotic leakage in four patients of the
      improvement group. They were with stable vital signs and the median hospital stay
      was 29.3 days. There was anastomotic leakage in five cases of the contol group
      and all of them had high fever and chest tightness. One among those five patients
      had transdermal placement of thoracic drainage tube and was cured, and four among
      those five patients had second debridement operation, with 3 cured and one death
      case. Except the one death case, the median hospital stay of the control group
      was 53.4 days, significantly longer than that of the improvement group (P <
      0.05). CONCLUSIONS: Although putting trans-abdominal-mediastinal drainage tube
      can not prevent the leakage of esophagogastric or esophago-jejunnal anastomosis,
      it can reduce the systemic inflammatory responses, death and painful suffering of
      the patients caused by anastomotic leakage.

PMID- 23159001
TI  - [Clinical observation of icotinib hydrochloride for patients with advanced non
      small cell lung cancer].
AB  - OBJECTIVE: To explore the efficacy and side effects of icotinib hydrochloride in
      the treatment of patients with advanced non-small cell lung cancer (NSCLC).
      METHODS: The efficacy and side effects of icotinib hydrochloride in treatment of
      59 cases with stage IV NSCIC and followed-up from March 2009 to January 2012 were
      retrospectively analyzed. RESULTS: Twenty seven patients (45.8%) showed partial
      response (PR), 17 patients (28.8%) achieved SD, and 15 (25.4%) had progressive
      disease. The objective response rate (ORR) was 45.8% (27/59), and disease control
      rate (DCR) was 74.6% (44/59). Among the 23 patients with EGFR mutation, ORR was
      73.9% (17/23), and DCR was 95.7% (22/23). Thirty six patients (61.0%) achieved
      remission of symptoms to varying degrees. The main symptoms relieved were cough,
      asthmatic suffocating, pain and hoarseness. The major adverse events were mild
      skin rash (35.6%) and diarrhea (15.3%). Others were dry skin, nausea and stomach
      problems. The efficacy of icotinib hydrochloride were related to the ECOG
      performance status, smoking history, EGFR mutation and rash significantly (P <
      0.05). CONCLUSIONS: Monotherapy with icotinib hydrochloride is effective and
      tolerable for patients with advanced NSCLC, especially with EGFR mutation.

PMID- 23159003
TI  - [Evaluation of early diagnosis and treatment of cancer].

PMID- 23159002
TI  - [Effectiveness and health economic analysis of strategies on cervical cancer
      screening and early diagnosis and treatment].
AB  - OBJECTIVE: To explore the appropriate strategies which are suitable for the areas
      with diverse health and economic resource settings in China by estimating the
      life outcomes and cost-effectiveness of several cervical cancer screening
      strategies. METHODS: Markov model was used to calculate the long-term
      effectiveness, utility, benefit and cost among screened and unscreened cohorts in
      rural and urban areas, and then analyses of cost-effectiveness, cost-utility and
      cost-benefit were performed. The assessed screening strategies were acetic acid
      of visual inspection combined with Lugol's iodine staining (VIA/VILI),
      conventional Pap smear and simple HPV DNA testing (careHPV) in rural areas, and
      conventional Pap smear, simple HPV DNA testing (careHPV), HPV DNA testing (HC2)
      and liquid-based cytology (LBC) alone or combined with HPV DNA testing (LBC+HC2)
      in urban areas. We estimated the life outcomes and cost-effectiveness of the
      above screening strategies at one-year, 3-year and 5-year intervals. RESULTS: All
      of the screening strategies were effective to decrease cervical cancer mortality
      and to increase life years, with a trend of shorter screening interval having
      better effectiveness. However, no matter in urban or rural areas, compared with
      careHPV testing at 5-year interval, the costs of other screening strategies were
      1.28 - 13.86 folds, 1.31 - 14.14 folds, and 1.27 - 12.80 folds higher to avoid
      one death, to save a year of life, and a QALY, and the benefit per cost of other
      screening strategies was 9.9%-90.2%. CONCLUSIONS: careHPV testing at 5-year
      interval has the best cost-effectiveness performance and the highest benefit-cost
      ratio with the moderate life outcomes. It is the optimal cervical cancer
      screening strategy to be generalized in our country. careHPV testing at 3 years
      interval can be considered in more developed areas to achieve better
      effectiveness.

PMID- 23159004
TI  - [Are physicians in primary care aware of the lack of evidence for population
      based screening for prostate cancer?].

PMID- 23159005
TI  - Thermodynamic analysis on the binding of heavy metals onto extracellular
      polymeric substances (EPS) of activated sludge.
AB  - Metal binding to microbial extracellular polymeric substances (EPS) greatly
      influences the distribution of heavy metals in microbial aggregates, soil and
      aquatic systems in nature. In this work, the thermodynamic characteristics of the
      binding between aqueous metals (with copper ion as an example) and EPS of
      activated sludge were investigated. Isothermal titration calorimetry was employed
      to estimate the thermodynamic parameters for the binding of Cu2+ onto EPS, while
      three-dimensional excitation-emission matrix (EEM) fluorescence spectroscopy with
      parallel factor analysis was used for quantifying the complexation of Cu2+ with
      the EPS. The binding mechanisms were further explored by X-ray absorption fine
      structure (XAFS) and Fourier transform infrared (FTIR) spectroscopy analysis. The
      results show that the proteins and humic substances in EPS were both strong
      ligands for Cu2+. The binding capacity N, binding constant K, binding enthalpy
      DeltaH were calculated as 5.74 * 10-2 mmol/g, 2.18 * 105 L/mol, and -11.30
      kJ/mol, respectively, implying that such a binding process was exothermic and
      thermodynamically favorable. The binding process was found to be driven mainly by
      the entropy change of the reaction. A further investigation shows that Cu2+ bound
      with the oxygen atom in the carboxyl groups in the EPS molecules of activated
      sludge. This study facilitates a better understanding about the roles of EPS in
      protecting microbes against heavy metals.

PMID- 23159006
TI  - Nitrous oxide emissions and dissolved oxygen profiling in a full-scale nitrifying
      activated sludge treatment plant.
AB  - This paper reports findings from online, continuous monitoring of dissolved and
      gaseous nitrous oxide (N2O), combined with dissolved oxygen (DO) and ammonia
      loading, in a full-scale nitrifying activated sludge plant. The study was
      conducted over eight weeks, at a 210,000 population equivalent sewage treatment
      works in the UK. Results showed diurnal variability in the gaseous and dissolved
      N2O emissions, with hourly averages ranging from 0 to 0.00009 kgN2O-N/h for
      dissolved and 0.00077-0.0027 kgN2O-N/h for gaseous nitrous oxide emissions
      respectively, per ammonia loading, depending on the time of day. Similarly, the
      spatial variability was high, with the highest emissions recorded immediately
      after the anoxic zone and in the final pass of the aeration lane, where ammonia
      concentrations were typically below 0.5 mg/L. Emissions were shown to be
      negatively correlated to dissolved oxygen, which fluctuated between 0.5 and 2.5
      mgO2/L, at the control set point of 1.5 mgO2/L. The resulting dynamic DO
      conditions are known to favour N2O production, both by autotrophic and
      heterotrophic processes in mixed cultures. Average mass emissions from the lane
      were greater in the gaseous (0.036% of the influent total nitrogen) than in the
      dissolved (0.01% of the influent total nitrogen) phase, and followed the same
      diurnal and spatial patterns. Nitrous oxide emissions corresponded to over 34,000
      carbon dioxide equivalents/year, adding 13% to the carbon footprint associated
      with the energy requirements of the monitored lane. A clearer understanding of
      emissions obtained from real-time data can help towards finding the right balance
      between improving operational efficiency and saving energy, without increasing
      N2O emissions.

PMID- 23159007
TI  - An exploration of deaf women's access to mental health nurse education in the
      United Kingdom.
AB  - Historically deaf people have been denied access to professional nurse education
      due to a range of language, communication and ideological barriers. The following
      study was set in the North of England and draws upon the Western experience and
      knowledge base of deaf people's experience of access to professional education.
      The aim of this study was to understand the experiences of the first British Sign
      Language using deaf qualified nurses before they entered the Pre-registration
      Diploma in Nursing Programme, during the programme and after the programme as
      they progressed into professional nursing roles. The purpose of the study was to
      gather the nurses' thoughts and feelings about their experiences and to analyse
      these using thematic analysis within a narrative interpretive tradition against a
      backdrop of Jurgen Habermas' critical theory and Paulo Freire's critical
      pedagogy. By drawing out significant themes to structure a deeper understanding
      of the nurses' unique positions, they offer a model for inclusive education
      practice that would support deaf people and people from minority groups into
      nursing and other health care professions. The signed narratives were video
      recorded and interpreted into written English transcripts which were then
      analysed to discover the underlying themes using Boyatzis' (1998) thematic
      analysis. The findings are set against an historical and contemporary setting of
      deaf people in Western society, their experiences of education, health and
      employment. These unique findings illustrate the significance of an accessible
      language environment for the nurses, the role of the organisation in ensuring
      access for the nurses and the impact of barriers to education and the clinical
      environment. The implications for education and practice supports the need to
      analyse the workforce required in deaf services, to scrutinize the access
      provided, to develop cultural competence skills, enhance the use of additional
      support mechanisms, generate accessible communities of practice and to draw upon
      the deaf nurses' own ideas and perspectives to develop accessible provision.

PMID- 23159008
TI  - Crossing professional barriers with peer-assisted learning: undergraduate
      midwifery students teaching undergraduate paramedic students.
AB  - BACKGROUND: Peer assisted learning (PAL) has been shown in undergraduate
      programmes to be as effective as learning from instructors. PAL is a shared
      experience between two learners often with one being more senior to the other but
      usually both are studying within the same discipline. Interprofessional education
      occurs when two or more professionals learn with, from and about each other.
      Benefits of PAL in an interprofessional context have not been previously
      explored. As part of a final year education unit, midwifery students at Monash
      University developed workshops for second year undergraduate paramedic students.
      The workshops focused on care required during and after the birth of the baby.
      AIM: To investigate the benefits of an interprofessional PAL for both midwifery
      and paramedic students. METHODS: Data for this project were obtained by both
      quantitative and qualitative methods. Questionnaires were distributed to both
      cohorts of students to explore experiences of peer teaching and learning. Results
      were analysed using Statistical Package for Social Sciences (SPSS). Focus groups
      were conducted separately with both cohorts of students and transcripts analysed
      using a thematic approach. FINDINGS: Response rates from the midwifery and
      paramedic students were 64.9% and 44.0% respectively. The majority of students
      regardless of discipline enjoyed the interprofessional activity and wanted more
      opportunities in their curricula. After initial anxieties about teaching into
      another discipline, 97.3 (n = 36) of midwifery students thought the experience
      was worthwhile and personally rewarding. Of the paramedic students, 76.9% (n =
      60) reported enjoying the interaction. The focus groups supported and added to
      the quantitative findings. Both midwifery and paramedic students had a new-found
      respect and understanding for each other's disciplines. Midwifery students were
      unaware of the limited knowledge paramedics had around childbirth. Paramedic
      students admired the depth of knowledge displayed by the midwifery students.
      IMPLICATIONS: This study indicates both educational and professional benefits for
      undergraduate students from different disciplines having shared PAL activities.

PMID- 23159009
TI  - Intrathecal morphine 100 and 200 MUg for post-cesarean delivery analgesia: a
      trade-off between analgesic efficacy and side effects.
AB  - INTRODUCTION: Intrathecal morphine is highly effective for post-cesarean
      analgesia; however, the optimal dose is yet to be established. The aim of this
      study was to compare analgesia and side effects after a change in institutional
      practice to give 200 MUg rather than 100 MUg. METHODS: We conducted a
      retrospective chart review of 241 patients who had an elective cesarean delivery
      and received either 100 or 200 MUg of intrathecal morphine. The primary outcome
      variables were mean and peak verbal pain scores (0-10) and analgesic use
      (milligram-morphine equivalents). Postoperative administration of antiemetics,
      antipruritics and episodes of nausea or vomiting were recorded. Data are reported
      as mean+/-SD or percentages with P<0.05 considered statistically significant.
      RESULTS: Women receiving intrathecal morphine 200 MUg had lower pain scores and
      opioid use compared with morphine 100 MUg. Mean verbal pain scores were 1.6+/-1.1
      versus 2.0+/-1.1 (P=0.01) and peak verbal pain scores were 4.9+/-2.0 versus 5.6+/
      1.8, respectively (P=0.008). The group receiving 200 MUg used less opioids in the
      first 24 h after surgery (44+/-35 versus 54+/-35 milligram-morphine equivalents,
      respectively, P=0.04) and received less intravenous opioids (18% versus 30%,
      P=0.02). However, women receiving intrathecal morphine 200 MUg had more nausea
      (mean number of episodes of nausea 1.9+/-1.3 versus 1.6+/-1.3, P=0.037) and used
      more antiemetics (52% versus 24%, P<0.0001). CONCLUSIONS: Intrathecal morphine
      200 MUg provided better analgesia but with more nausea compared with morphine 100
      MUg. Our results can be used to help guide intrathecal morphine dosing in
      cesarean delivery based on patient preference for analgesia versus side effects.

PMID- 23159010
TI  - Reduced cerebrospinal fluid level of thyroxine in patients with Alzheimer's
      disease.
AB  - BACKGROUND: Little is known of the association between thyroid hormones in the
      central nervous system and Alzheimer's disease (AD). We determined thyroid
      hormone levels in serum and cerebrospinal fluid (CSF) in a well-defined
      homogeneous mono-center population. METHODS: Fifty-nine consecutive patients
      under primary evaluation for cognitive impairment were recruited. The
      participants included patients with AD or mild cognitive impairment (MCI)
      diagnosed with AD upon follow-up (n=31), patients with stable MCI (SMCI, n=13),
      patients with other dementias (n=15), and healthy controls (n=19). Thyroid
      hormones in serum and CSF and AD biomarkers in CSF were analyzed using
      established immunochemical assays. Cognitive impairment was estimated using mini
      mental state examination (MMSE). RESULTS: Serum levels of free and total
      thyroxine (T4) and triiodothyronine (T3) were similar in all groups whereas a
      marginal increase in serum thyroid-stimulating hormone (TSH) level was observed
      in the AD patients. The CSF level of total T4 was decreased in patients with AD
      and other dementias compared to SMCI (both P=0.01) and healthy controls (both
      P=0.001), whereas CSF levels of TSH and total T3 were unchanged. In the total
      study population, CSF total T4 level correlated positively with MMSE score
      (r=0.26, P<0.05) and negatively with CSF total-tau (T-Tau) level (r=-0.23,
      P<0.05). CONCLUSION: Patients with AD as well as other dementias had signs of
      mild brain hypothyroidism, which could only to a small extent be detected in
      serum values.

PMID- 23159011
TI  - Oxytocin, brain physiology, and functional connectivity: a review of intranasal
      oxytocin fMRI studies.
AB  - In recent years the neuropeptide oxytocin (OT) has become one of the most studied
      peptides of the human neuroendocrine system. Research has shown widespread
      behavioural effects and numerous potential therapeutic benefits. However, little
      is known about how OT triggers these effects in the brain. Here, we discuss some
      of the physiological properties of OT in the human brain including the long half
      life of neuropeptides, the diffuse projections of OT throughout the brain and
      interactions with other systems such as the dopaminergic system. These properties
      indicate that OT acts without clear spatial and temporal specificity. Therefore,
      it is likely to have widespread effects on the brain's intrinsic functioning.
      Additionally, we review studies that have used functional magnetic resonance
      imaging (fMRI) concurrently with OT administration. These studies reveal a
      specific set of 'social' brain regions that are likely to be the strongest
      targets for OT's potential to influence human behaviour. On the basis of the fMRI
      literature and the physiological properties of the neuropeptide, we argue that OT
      has the potential to not only modulate activity in a set of specific brain
      regions, but also the functional connectivity between these regions. In light of
      the increasing knowledge of the behavioural effects of OT in humans, studies of
      the effects of OT administration on brain function can contribute to our
      understanding of the neural networks in the social brain.

PMID- 23159012
TI  - Neonatal amygdala lesions alter basal cortisol levels in infant rhesus monkeys.
AB  - The amygdala is mostly thought to exert an excitatory influence on the
      hypothalamic-pituitary-adrenal (HPA) axis, although its role regulating HPA basal
      tone is less clear, particularly during primate development. The current study
      examined the effects of neonatal amygdala lesions on basal HPA function and the
      postnatal testosterone (T) surge of rhesus monkeys reared with their mothers in
      large outdoor social groups. An early morning basal blood sample was collected at
      2.5 months of age, whereas at 5 months samples were collected not only at
      sunrise, but also at mid-day and sunset to examine the diurnal rhythm of
      cortisol. At 2.5 months of age sham-operated males exhibited higher cortisol than
      females, but this sex difference was abolished by neonatal amygdalectomy, with
      lesioned males also showing lower basal cortisol than controls. Although neonatal
      amygdalectomy did not alter the postnatal T surge, there was a positive
      relationship between T and basal cortisol levels. At 5 months of age, neither the
      sex difference in cortisol, nor its correlation with T levels were apparent any
      longer. Instead, the diurnal cortisol rhythm of both males and females with
      amygdalectomy showed a blunted decline from mid-day to sunset compared to
      controls. These results indicate that neonatal amygdala damage alters basal HPA
      function in infant rhesus monkeys, affecting males only at early ages (at 2.5
      months), while leaving the postnatal T surge intact, and resulting in a flattened
      diurnal rhythm in both genders at the later ages. Thus, the primate amygdala has
      a critical influence on the HPA axis in the first few months of life.

PMID- 23159013
TI  - Computationally estimated apolipoproteins B and A1 in predicting cardiovascular
      risk.
AB  - OBJECTIVE: Apolipoproteins B (apoB) and A1 (apoA1) may be better markers of
      atherosclerosis than serum lipids. We used computational methods to estimate apoB
      and apoA1 from serum total cholesterol, HDL-cholesterol and triglycerides and
      tested their clinical value in comparison to measured apoB and apoA1 values.
      METHODS: ApoB and apoA1 were measured with standard methods and estimated based
      on neural network regression models in 2166 young adult with data on carotid
      artery intima-media thickness (cIMT). RESULTS: Correlations between estimated and
      measured apoB and apoA1 were r = 0.98 and r = 0.95, respectively. ApoB/apoA1
      ratio (both measured and estimated) associated with cIMT in multivariable models,
      and predicted cIMT at all levels of LDL-cholesterol concentration. Strong
      correlations between the estimated apolipoproteins and those measured from
      fasting samples were replicated in over 15,000 Caucasian subjects (r = 0.93-0.96
      for apoB and r = 0.91-0.92 for apoA1). Correlations with cIMT were replicated in
      over 2000 individuals. Estimated apoB/apoA1-ratio calculated from non-fasting
      lipids in over 20,000 individuals in the INTERHEART study was better than any of
      the cholesterol measures for estimation of the myocardial risk. CONCLUSIONS:
      Serum cholesterol, HDL-cholesterol and triglycerides can be used to compute
      clinically useful estimates of apoB and apoA1. Using this methodology, estimates
      of apolipoproteins could be routinely added to laboratory reports to complement
      lipoprotein lipids in risk assessment.

PMID- 23159015
TI  - Intramuscular hemangioma of the scalene musculature masquerading as a
      paraganglioma: a case series.
AB  - Intramuscular hemangiomas (IMHs) are uncommon benign vascular lesions, which
      develop in skeletal muscle. Herein, two cases of IMHs involving the cervical
      scalene musculature are presented. Such lesions are exceedingly rare, and can be
      difficult to distinguish from vagal paragangliomas based on clinical
      presentation, exam, and radiography. Complete surgical excision is the treatment
      of choice, and was successful in our two index patients. While rare, IMHs of the
      scalene muscles should be considered in the differential diagnosis of deep neck
      space masses.

PMID- 23159014
TI  - An investigation of excess residual cytoplasm in human spermatozoa and its
      distinction from the cytoplasmic droplet.
AB  - Recent studies have shown cytoplasmic droplets to be normal morphological
      occurrences in human male spermatozoa. When the cytoplasm around the sperm
      midpiece is present in large amounts, however, pathological effects may
      transpire. The cytoplasmic droplet then becomes known as excess residual
      cytoplasm, which can impair overall sperm function and produce higher levels of
      reactive oxygen species, potentially leading to male infertility. Though the
      distinction between cytoplasmic droplets and excess residual cytoplasm has been
      made, some studies fail to recognize the difference and incorrectly label the
      latter as a cytoplasmic droplet. This review attempts to clarify excess residual
      cytoplasm's effect on fertility, examine the enzymes responsible, and suggest
      tests and possible treatment options for those affected by this defect.

PMID- 23159016
TI  - A case of necrotizing sialometaplasia involving bilateral parotid glands.
AB  - Necrotizing sialometaplasia of the parotid gland is infrequent and can be
      mistaken as a malignant disease. Its etiology is thought to be an insufficient
      blood supply. Bilateral involvement of this disease in parotid glands has been
      rarely reported in the English literature. We report a case of necrotizing
      sialometaplasia diagnosed after superficial parotidectomy due to bilateral
      parotid masses in a 69-year old heavy smoking female.

PMID- 23159017
TI  - Developing and evaluating complex interventions: reflections on the 2008 MRC
      guidance.
AB  - This invited commentary reflects on the impact of the MRC's revised guidance for
      the development and evaluation of complex interventions, and considers some of
      the criticisms that have been published in response to the guidance.

PMID- 23159019
TI  - [Orotracheal intubation difficulty with lighted stylet: correlation of body mass
      index and neck circumference].
AB  - OBJECTIVES: To evaluate the difficulty of intubation with a lighted stylet by
      correlating the body mass index (BMI) with the neck or cervical circumference
      (CC), and to establish the values of BMI and CC that could help identify a
      possible difficult intubation with this device. PATIENTS AND METHODS: An
      observational and correlational study was performed on selected patients by
      consecutive sampling who were intubated using the lighted stylet. Variables such
      as age, gender, ASA physical status, BMI, CC, transillumination intensity,
      Cormack-Lehane grade, and Mallampati scores, were recorded. Multivariable
      analyses were performed. RESULTS: 103 patients were included. The mean age of the
      patients was 39.0 +/- 16.6 years, BMI 28.6 +/- 6.8 kg/m2 (33% obese and 29,1%
      overweight), CC 37.8 +/- 4.6 cm. Those patients who presented difficulty for
      intubation had a CC 39.9 +/- 5.2 cm (P <= 0.05), and a BMI 33.8 +/- 7.6 kg/m2 (P
      = 0.01). CONCLUSION: A lineal correlation exists between a BMI above 33 kg/m2
      and/or a CC greater than 40 cm and a difficult intubation using lighted stylet.
      Another method other than transillumination is recommended for orotracheal
      intubation in a patient with both characteristics.

PMID- 23159018
TI  - A staff intervention targeting resident-to-resident elder mistreatment (R-REM) in
      long-term care increased staff knowledge, recognition and reporting: results from
      a cluster randomized trial.
AB  - BACKGROUND: Elder abuse in long-term care has received considerable attention;
      however, resident-to-resident elder mistreatment (R-REM) has not been well
      researched. Preliminary findings from studies of R-REM suggest that it is
      sufficiently widespread to merit concern, and is likely to have serious
      detrimental outcomes for residents. However, no evidence-based training,
      intervention and implementation strategies exist that address this issue.
      OBJECTIVES: The objective was to evaluate the impact of a newly developed R-REM
      training intervention for nursing staff on knowledge, recognition and reporting
      of R-REM. DESIGN: The design was a prospective cluster randomized trial with
      randomization at the unit level. METHODS: A sample of 1405 residents (685 in the
      control and 720 in the intervention group) from 47 New York City nursing home
      units (23 experimental and 24 control) in 5 nursing homes was assessed. Data were
      collected at three waves: baseline, 6 and 12 months. Staff on the experimental
      units received the training and implementation protocols, while those on the
      comparison units did not. Evaluation of outcomes was conducted on an intent-to
      treat basis using mixed (random and fixed effects) models for continuous
      knowledge variables and Poisson regressions for longitudinal count data measuring
      recognition and reporting. RESULTS: There was a significant increase in knowledge
      post-training, controlling for pre-training levels for the intervention group
      (p<0.001), significantly increased recognition of R-REM (p<0.001), and
      longitudinal reporting in the intervention as contrasted with the control group
      (p=0.0058). CONCLUSIONS: A longitudinal evaluation demonstrated that the training
      intervention was effective in enhancing knowledge, recognition and reporting of R
      REM. It is recommended that this training program be implemented in long-term
      care facilities.

PMID- 23159020
TI  - [Use of prothrombin complex concentrate in a warfarin anticoagulated patient
      subjected to emergency abdominal surgery].

PMID- 23159021
TI  - [Comparison between VAMA((r)) and Berman((r)) cannulas for fibroscopic
      orotracheal intubation in anaesthetised patients].
AB  - OBJECTIVES: In fibroscopic intubation, the fact of achieving a direct view in
      real time does not guarantee the correct advance of the endotracheal tube (ET) to
      its intratracheal position. The use of oral cannulas helps in achieving a free
      airway in order to pass the fibroscope and the ET. This study compares the
      VAMA((r)) (V) and Berman((r)) (B) cannulas as regards the time required for the
      intubation, fibroscopic view, and the ease in positioning the ET. PATIENTS AND
      METHODS: 90 patients with no signs of difficult airway were randomised into 2
      groups, Berman((r)) (B) and VAMA((r)) (V), depending on the type of cannula
      employed. After inducing general anaesthesia, they were intubated using a
      flexible fibroscope. The fibroscope and intubation times were recorded, as well
      as the quality of the fibroscopic view, and the level of difficulty in
      positioning the ET. RESULTS: No statistically significant differences were
      observed between the cannulas, although the intubation time (P=.292) and the
      difficulty found in positioning the ET were slightly less (P=.447) in the
      VAMA((r)) group compared to the Berman((r)) group. The vision quality was good
      with both devices, with only some degree of obstruction being encountered in only
      22% of the patients. In no case was there complete obstruction, thus all the
      patients could be intubated correctly. CONCLUSIONS: The VAMA((r)) cannula is an
      effective alternative to the classic cannulas for fibreoptic assisted intubation.
      Furthermore, the novel design provides advantages for the correct orientation of
      the fiberscope and the withdrawal of the cannula after intubation.

PMID- 23159022
TI  - Subjective and objective vocal parameters in women with polycystic ovary
      syndrome.
AB  - INTRODUCTION: Despite the relatively high prevalence of the polycystic ovary
      syndrome (PCOS) affecting up to 15% of all women of reproductive age, only little
      is known about vocal changes related to this endocrinologic disorder that is
      characterized by biochemical or clinical hyperandrogenism, impaired cycles,
      and/or polycystic ovaries. The aim of our study was to describe objective and
      subjective vocal changes in women with a diagnosed PCOS compared with a control
      group. MATERIALS AND METHODS: Our study group comprised 34 women-24 cases with
      confirmed PCOS and 10 controls in whom PCOS was excluded. A complete
      endocrinologic laboratory status was obtained by all participants; study
      procedures included a videolaryngostroboscopy, voice recording, and completion of
      the German version of the Voice Handicap Index. RESULTS: A trend toward lower
      mean fundamental frequency was detectable, but this failed statistical
      significance. No differences were found in the objective and subjective voice
      parameters. CONCLUSION: Elevated serum levels of androgens, as found in women
      with PCOS, were shown not to have an impact on the subjective and objective voice
      parameters.

PMID- 23159023
TI  - Phase difference of vocally healthy subjects in high-speed digital imaging
      analyzed with laryngotopography.
AB  - BACKGROUND: To elucidate the vibratory patterns of the vocal folds in normophonic
      subjects, we conducted a prospective study with laryngotopography, an analyzing
      technique for high-speed digital imaging to intuitively grasp spatial
      characteristics of vocal fold vibrations by pixel-wise discrete Fourier transform
      for brightness curve. MATERIALS AND METHODS: Vocally healthy volunteer subjects
      with neither vocal complaint nor history of laryngeal diseases were divided into
      young (aged 35 years and younger) and elderly groups (aged 65 years and older),
      and high-speed digital images of phonations at a conversational frequency were
      analyzed with laryngotopography: phase differences (PDs) in the anterior
      posterior (longitudinal) direction and in the left-right (lateral) direction were
      assessed. RESULTS: Twenty-six young subjects (nine men and 17 women with a mean
      age of 27 years) and 20 elderly subjects (eight men and 12 women with a mean age
      of 73 years) were assigned to our study. In longitudinal PD, posterior-to
      anterior opening type was significantly frequent in young women (all subjects:
      43% and young women: 94%; P<0.001), whereas anterior-to-posterior opening type
      was significantly frequent in elderly men (all subjects: 39% and elderly men:
      88%; P<0.001). There were no age- or gender-related differences in lateral PD
      (all subjects: 65%; P=0.880). DISCUSSIONS: Both longitudinal and lateral PDs were
      widely observed even in vocally healthy subjects. Furthermore, the age- and
      gender-specific characteristics were also classified. Laryngotopography serves as
      a powerful tool to quantitatively characterize the vibratory patterns of vocal
      folds in vocally healthy subjects.

PMID- 23159024
TI  - The interarytenoid spatial relationship: accuracy and interrater reliability for
      determining sidedness in cases of unilateral adductor paresis.
AB  - BACKGROUND/OBJECTIVE: When adductor vocal fold paresis manifests without obvious
      motion impairment, identifying the paretic side can be challenging. Although
      increased vocal fold waveform amplitude ("floppiness") on videostroboscopy may be
      helpful, it has been shown to have low interrater reliability. We have found that
      the interarytenoid spatial relationship (IASR) can often accurately be used to
      predict the sidedness of electromyography (EMG)-determined unilateral adductor
      (thyroarytenoid/lateral cricoarytenoid [TA/LCA]) paresis. The goal of this study
      was to determine if a series of otolaryngology residents could learn to assess
      the IASR on videostroboscopy and use the IASR to identify the side of EMG
      documented adductor paresis with high accuracy and interrater reliability. STUDY
      DESIGN: Otolaryngology resident population surveys. METHODS: Ten residents were
      given videostroboscopy images on abduction/adduction from 10 consecutive patients
      with EMG-documented unilateral TA/LCA paresis and asked to identify the paretic
      side in a pretest. The IASR was then conceptually introduced to the
      otolaryngology residents in a brief presentation. Posttesting was then performed
      and used to assess EMG-based accuracy and interrater reliability. RESULTS: Before
      the IASR presentation, otolaryngology residents accurately identified the paretic
      side in 63% (95% confidence interval [CI]: 56-70%) of cases. In the posttest
      session, the residents accurately identified the paretic side in 93% (95% CI: 87
      99%) of cases, and interrater reliability was 0.873. CONCLUSIONS: The IASR may be
      useful in determining sidedness in cases of unilateral TA/LCA paresis. Further
      studies are needed to determine the sensitivity and specificity of the IASR for
      determining sidedness of unilateral TA/LCA paresis with intact mobility.

PMID- 23159025
TI  - Use of the rabbit larynx in an excised larynx setup.
AB  - OBJECTIVE: To modify the excised larynx bench apparatus to accommodate
      experiments with rabbit larynges. STUDY DESIGN: Methodological study using ex
      vivo rabbit larynges. METHODS: Rabbit larynges (n=5) were dissected and mounted
      on a custom-made phonatory apparatus. The arytenoids were adducted by rods, and
      humidified air was passed through the larynx to elicit vocal fold vibration.
      Acoustic, aerodynamic, electroglottographic (EGG), and videokymographic data were
      collected for each larynx. The same data were collected for five canine larynges
      for the purpose of comparison, and coefficients of variation were calculated for
      each parameter in both models. RESULTS: Reliable phonation was achieved in each
      larynx. Acoustic fundamental frequency (F(0)), percent jitter, percent shimmer,
      signal-to-noise ratio, pressure and flow at phonation onset and offset; and F(0),
      closed quotient, speed quotient, jitter, shimmer, and contact quotient, as
      recorded by EGG; and mucosal wave amplitude and phase difference are reported for
      rabbit larynges. Coefficients of variation for each parameter are similar in
      magnitude between the two models. CONCLUSION: We developed a method for recording
      reliable acoustic, aerodynamic, videokymographic, and EGG data from rabbit
      larynges. When data obtained from leporine larynges were compared with data from
      canine larynges, the intralarynx variability of rabbit larynges was found to be
      similar to that of canine larynges.

PMID- 23159026
TI  - Oropharyngeal pH monitoring for laryngopharyngeal reflux: is it a reliable test
      before therapy?
AB  - OBJECTIVE: Current methods of measuring pharyngeal pH are problematic. The aim of
      the study was to assess the ability of the oropharyngeal pH monitoring (Restech)
      in predicting the response to proton pump inhibitor (PPI) therapy in patients
      with gastroesophageal reflux disease-related laryngopharyngeal symptoms. STUDY
      DESIGN: The study design is prospective and uncontrolled. METHODS: Twenty-two
      consecutive naive patients with chronic laryngeal symptoms were enrolled. Reflux
      symptom index, fibrolaryngoscopy, and 24-hour oropharyngeal pH monitoring were
      performed. Both patients and laryngoscopist were blinded by the results of
      Restech. All the patients were given a 3-month therapy with pantoprazole of 40mg
      twice a day and then repeated both the reflux symptom index and
      fibrolaryngoscopic evaluation. Patients were considered as responders if a five
      point decrease in symptom score was recorded. RESULTS: Thirteen of the 22
      patients (59.1%) responded to therapy. Laryngoscopic findings did not correlate
      with the clinical improvement after the 3 months of PPI. Nine patients (40.9%)
      had a pathologic Restech study, and all resulted responsive to PPI; nine patients
      (40.9%) with a negative Restech were nonresponsive to PPI, and four patients
      (18.2%) despite a negative Restech resulted responsive to therapy. Responsive
      patients showed both a higher oropharyngeal acid exposure in orthostatic position
      and a higher Ryan score, compared with nonresponders (49.74+/-58.11 vs 2.12+/
      0.0, P=0.002). Considering responsiveness to medical therapy as the gold standard
      of laryngopharyngeal reflux (LPR) for the diagnosis of LPR, Restech showed a
      sensitivity of 69% and a specificity of 100%. CONCLUSIONS: The high specificity
      and reasonable sensitivity of this technique make the Restech an interesting tool
      before therapy of patients with pharyngoesophageal reflux.

PMID- 23159027
TI  - Characterization of voice disorders in deployed and nondeployed US army soldiers.
AB  - OBJECTIVES/HYPOTHESIS: To evaluate voice disorder differences between deployed
      and nondeployed US army soldiers. STUDY DESIGN: Cross-sectional study. METHODS:
      More than 1.3 million health records of active duty US army soldiers with no
      history of dysphonia were queried for voice disorder diagnoses over a 3.5-year
      period. A sample of 292 soldiers was further evaluated for known factors linked
      to dysphonia. RESULTS: US army soldiers were 1.13 times more likely to have a
      diagnosis of dysphonia if they were deployed. Risk factors and exposures common
      to patients with dysphonia were not statistically different between deployed and
      nondeployed soldiers. Additionally, the type of dysphonia diagnosis was not
      significantly different between deployed and nondeployed soldiers. CONCLUSIONS:
      US army soldiers deployed to war zones are more likely to be diagnosed with
      dysphonia. None of the reviewed parameters accounted for the difference in
      dysphonia rate between deployed and nondeployed soldiers, suggesting that
      occupational exposures of deployed soldiers account for the increase in the
      diagnoses of dysphonia.

PMID- 23159028
TI  - Morphology of fetal vocal fold and associated structures.
AB  - This study is the first detailed qualitative morphologic description of the vocal
      fold and its associated structures (false vocal fold, larynx ventricle,
      epithelium, mucous glands, blood vessels, and vocal ligament) of a human fetus
      aged 25 weeks. In addition, a quantitative analysis of thyroarytenoid (TA) muscle
      fiber orientation is presented to investigate similarities with adult TA.
      Histologic cross sections from the vocal fold and the anterior, middle, and
      posterior regions of the TA muscle were examined bilaterally, and both
      qualitative and quantitative analyses show that the vocal fold and most of the
      associated structures are completely established in the studied sample.

PMID- 23159029
TI  - What makes a good voice for radio: perceptions of radio employers and educators.
AB  - AIM: To inform vocal training and management of voice disorders of professional
      radio performers in Australia by determining radio employers' and educators'
      qualitative perceptions on (1) what makes a good voice for radio and (2) what
      communication characteristics are important when employing radio performers.
      METHOD: Radio employers and educators (n=9) participated in semistructured
      interviews. Interview transcripts were coded line-by-line and analyzed for
      qualitative themes using principles of grounded theory. RESULTS/IMPLICATIONS:
      Radio performers sound easy-on-the-ear, natural, and have an ability to read and
      produce voices that suit the station. Many of these characteristics make them
      sound different to radio voices in the past. Content and personality are now also
      more significant than voice characteristics. A multidimensional model of these
      characteristics is presented. The model has implications for the training and
      management of voice disorders in radio performers and will guide future
      quantitative research on the vocal features of this population.

PMID- 23159030
TI  - A comparison of the voice handicap index-10 scores between medical and musical
      theater students.
AB  - OBJECTIVE: Elite professional voice users experience a high vocal load and if
      voice quality deteriorates, their livelihoods are affected. Our aim was to assess
      how an elite professional voice user group, musical theater students (n=49),
      perceive their voices in comparison with medical students (n=43). STUDY DESIGN:
      Cross-sectional study. METHODS: Participants completed a confidential
      questionnaire including demographics and the Voice Handicap Index-10 (VHI-10) in
      September 2010. RESULTS: Response rate was 100% (92/92). The mean age of the
      medical students was 25 years and of musical theater students was 20 years. The
      mean overall VHI-10 score was higher in musical theater students compared with
      that of medical students (mean score, 5.56 and standard deviation [SD], 4.13 vs
      mean score, 3.79 and SD, 3.02, P=0.02), particularly in three VHI-10 items: voice
      strain, lack of clarity, and being upset from voice problem (mean score, 0.82 and
      SD, 0.86 vs mean score, 0.44 and SD, 0.67, P=0.02; mean score, 0.92 and SD, 0.89
      vs mean score, 0.53 and SD, 0.70, P=0.02; and mean score, 0.49 and SD, 0.79 vs
      mean score, 0.07 and SD, 0.26, P=0.001, respectively). Furthermore, musical
      theater students report higher possible voice problems in the past (6/43 [14%],
      21/49 [43%], P=0.002). CONCLUSIONS: In this small group, musical theater students
      report more handicap compared with medical students. It is possible that this
      difference may be because of the musical theater students experiencing greater
      voice use over time or better recognition of potential voice problems. This may
      mean that we need to do more to protect student's voices by optimizing vocal care
      during their training, without neglecting the vocal needs of other students.

PMID- 23159031
TI  - Influence on spectral energy distribution of emotional expression.
AB  - PURPOSE: The aim of this study was to determine the influence of emotional
      expression in spectral energy distribution in professional theater actors. STUDY
      DESIGN: The study design is a quasi-experimental study. METHOD: Thirty-seven
      actors, native Spanish speakers, were included. All subjects had at least 3 years
      of professional experience as a theater actor and no history of vocal pathology
      for the last 5 years. Participants were recorded during a read-aloud task of a
      230-word passage, expressing six different emotions (happiness, sadness, fear,
      anger, tenderness, and eroticism) and without emotion (neutral state). Acoustical
      analysis with long-term average spectrum included three variables: the energy
      level difference between the F(1) and fundamental frequency (F(0)) regions, ratio
      between 1-5kHz and 5-8kHz, and alpha ratio. RESULTS: All the different emotions
      differ significantly from the neutral state for alpha ratio and 1-5/5-8kHz ratio.
      Only significant differences between "joy," "anger," and "eroticism" were found
      for L1-L0 ratio. Statistically significant differences between genders for the
      three acoustical variables were also found. CONCLUSION: The expression of emotion
      impacts the spectral energy distribution. On the one hand emotional states
      characterized by a breathy voice quality such as tenderness, sadness, and
      eroticism present a low harmonic energy above 1kHz, high glottal noise energy,
      and more energy on F(0) than overtones. On the other hand, emotional states such
      as joy, anger, and fear are characterized by high harmonic energy greater than
      1kHz (less steep spectral slope declination), low glottal noise energy, and more
      energy on the F(1) than F(0) region.

PMID- 23159032
TI  - A preliminary study on the use of vocal function exercises to improve voice in
      male-to-female transgender clients.
AB  - OBJECTIVES: This study explores the outcomes of symptomatic voice treatment plus
      Stemple's vocal function exercises (VFEs) for a group of male-to-female (MTF)
      transgender (TG) clients seeking voice feminization. Both acoustic and perceptual
      outcomes were assessed, in addition to the clients' attitudes toward VFE. DESIGN:
      Prospective treatment study. METHOD: Three MTF TG clients plus three control
      female speakers and three control male speakers served as subjects. All provided
      a variety of speech samples. The TG clients underwent symptomatic voice therapy
      for 6 weeks, while simultaneously performing the VFE protocol. At the end of
      therapy, the TG clients provided posttreatment voice samples. All voice samples
      were analyzed for speaking fundamental frequency (SFF), SFF upper and lower
      limits, and the first three formants of /i/. A CD of pre- and posttreatment voice
      samples plus the control voices was presented to listeners for gender judgments
      and masculinity and femininity ratings. RESULTS: For acoustic measures, the TG
      subjects appeared more similar to the male control speakers in the pretest, and
      more similar to the female controls in the posttest. Perceptually, listeners
      continued to identify the TG subjects as male following therapy, although they
      were rated as significantly less masculine and more feminine. TG subjects were
      generally positive about the addition of VFE to their therapy experience.
      CONCLUSIONS: The addition of VFE did not appear to improve posttreatment outcomes
      compared with previous literature. It was suggested that both number of sessions
      and experience living full-time as a woman might be important variables in
      predicting progress in therapy.

PMID- 23159033
TI  - Evaluating voice characteristics of first-year acting students in Israel: factor
      analysis.
AB  - HYPOTHESIS: Acting students require diverse, high-quality, and high-intensity
      vocal performance from early stages of their training. Demanding vocal
      activities, before developing the appropriate vocal skills, put them in high risk
      for developing vocal problems. STUDY DESIGN: A retrospective analysis of voice
      characteristics of first-year acting students using several voice evaluation
      tools. METHODS: A total of 79 first-year acting students (55 women and 24 men)
      were assigned into two study groups: laryngeal findings (LFs) and no laryngeal
      findings, based on stroboscopic findings. Their voice characteristics were
      evaluated using acoustic analysis, aerodynamic examination, perceptual scales,
      and self-report questionnaires. Results obtained from each set of measures were
      examined using a factor analysis approach. RESULTS: Significant differences
      between the two groups were found for a single fundamental frequency (F(0))
      Regularity factor; a single Grade, Roughness, Breathiness, Asthenia, Strain
      perceptual factor; and the three self-evaluation factors. Gender differences were
      found for two acoustic analysis factors, which were based on F(0) and its
      derivatives, namely an aerodynamic factor that represents expiratory volume
      measurements and a single self-evaluation factor that represents the tendency to
      seek therapy. CONCLUSIONS: Approximately 50% of the first-year acting students
      had LFs. These students differed from their peers in the control group in a
      single acoustic analysis factor, as well as perceptual and self-report factors.
      No group differences, however, were found for the aerodynamic factors. Early
      laryngeal examination and voice evaluation of future professional voice users
      could provide a valuable individual baseline, to which later examinations could
      be compared, and assist in providing personally tailored treatment.

PMID- 23159034
TI  - Implementation of a quality care management system for patients with arthritis of
      the hip and knee.
AB  - The Orthopaedic Unit of the Repatriation General Hospital (RGH) in Adelaide,
      South Australia has implemented a quality care management system for patients
      with arthritis of the hip and knee. The system not only optimises conservative
      management but ensures that joint replacement surgery is undertaken in an
      appropriate and timely manner. This new service model addresses identified
      barriers to service access and provides a comprehensive, coordinated strategy for
      patient management. Over 4 years the model has reduced waiting times for initial
      outpatient assessment from 8 to 3 months and surgery from 18 to 8 months, while
      decreasing length of stay from 6.3 to 5.3 days for hips and 5.8 to 5.3 days for
      knees. The service reforms have been accompanied by positive feedback from
      patients and referring general practitioners in relation to the improved
      coordination of care and enhanced efficiency in service delivery.

PMID- 23159035
TI  - Autism and hospitals: a difficult match.

PMID- 23159036
TI  - The pediatrics milestones: a continuous quality improvement project is launched
      now the hard work begins!

PMID- 23159037
TI  - Barriers to evaluation for early intervention services: parent and early
      intervention employee perspectives.
AB  - OBJECTIVE: To explore barriers to early intervention (EI) evaluation among
      referred infants and toddlers. METHODS: We conducted semistructured interviews
      with parents of children referred for EI services and with EI staff. We
      purposively sampled families according to whether they received an EI evaluation.
      Families were recruited from a randomized controlled trial testing implementation
      of developmental screening. Parents filled out demographic surveys. Interviews
      were recorded, transcribed, and coded. We identified themes within and across
      respondent groups using modified grounded theory. RESULTS: We reached thematic
      saturation after interviewing 22 parents whose child was evaluated by EI, 22 not
      evaluated, and 14 EI employees. Mean child age at first referral was 16.7 months,
      and 80% were referred as the result of language concerns. We identified 5 primary
      themes: (1) Parents reported communication problems with their pediatrician,
      including misinterpreting reassurance and not understanding the referral process;
      (2) Many parents saw themselves as experts on their child's development and felt
      they should decide whether their child pursues EI services; (3) Some families
      preferred to wait for the developmental concern to resolve or work with their
      child on their own prior to seeking EI services; (4) For ambivalent parents,
      practical obstacles especially limited completion of evaluation, but highly
      motivated parents overcame obstacles; and (5) EI employees perceived that
      families avoid evaluation because they mistake EI for child protective services.
      CONCLUSIONS: Communication between pediatricians and families that addresses
      practical logistics, families' perceptions of their child's development and EI,
      and motivation to address developmental concerns may improve the completion of EI
      referrals.

PMID- 23159038
TI  - Characterization of human carbonic anhydrase XII stability and inhibitor binding.
AB  - Human carbonic anhydrase isozyme XII is a transmembrane protein that is
      overexpressed in many human cancers. Therefore CA XII is an anticancer drug
      target. However, there are few compounds that specifically target CA XII. The
      design of specific inhibitors against CA XII relies on the detailed understanding
      of the thermodynamics of inhibitor binding and the structural features of the
      protein-inhibitor complex. To characterize the thermodynamic parameters of the
      binding of known sulfonamides, namely ethoxzolamide, acetazolamide and
      trifluoromethanesulfonamide, we used isothermal titration calorimetry and
      fluorescent thermal shift assay. The binding of these sulfonamides to CA XII was
      buffer and pH-dependent. Dissection of protonation-deprotonation reactions of
      both the water molecule bound to the CA XII active site and the sulfonamide group
      of the inhibitor yielded the intrinsic thermodynamic parameters of binding, such
      as binding enthalpy, entropy and Gibbs free energy. Thermal shift assay was also
      used to determine CA XII stabilities at various pH and in the presence of buffers
      and salts.

PMID- 23159040
TI  - G-quadruplex DNA cleavage preference and identification of a perylene diimide G
      quadruplex photocleavage agent using a rapid fluorescent assay.
AB  - A rapid fluorescence assay for G-quadruplex DNA cleavage was used to investigate
      the preference of TMPyP4 photochemical and Mn.TMPyP4 oxidative cleavage. Both
      agents most efficiently cleave the c-Myc promoter G-quadruplex. Direct PAGE
      analysis of selected assay samples showed that for a given cleavage agent,
      different cleavage products are formed from different G-quadruplex structures.
      Cleavage assays carried out in the presence of excess competitor nucleic acid
      structures revealed the binding selectivity of cleavage agents, while comparisons
      with duplex cleavage efficiency employing a dual-labeled hairpin oligonucleotide
      revealed neither agent prefers G-quadruplex over duplex substrates. Finally, this
      assay was used to identify the perylene diimide Tel11 as a photocleavage agent
      for the c-Myc G-quadruplex.

PMID- 23159039
TI  - SIB-DOTA: a trifunctional prosthetic group potentially amenable for multi-modal
      labeling that enhances tumor uptake of internalizing monoclonal antibodies.
AB  - A major drawback of internalizing monoclonal antibodies (mAbs) radioiodinated
      with direct electrophilic approaches is that tumor retention of radioactivity is
      compromised by the rapid washout of iodo-tyrosine, the primary labeled catabolite
      for mAbs labeled via this strategy. In our continuing efforts to develop more
      versatile residualizing labels that could overcome this problem, we have designed
      SIB-DOTA, a prosthetic labeling template that combines the features of the
      prototypical, dehalogenation-resistant N-succinimidyl 3-iodobenzoate (SIB) with
      DOTA, a useful macrocyclic chelator for labeling with radiometals. Herein we
      describe the synthesis of the unlabeled standard of this prosthetic moiety, its
      protected tin precursor, and radioiodinated SIB-DOTA. An anti-EGFRvIII-reactive
      mAb, L8A4 was radiolabeled with [(131)I]SIB-DOTA in 27.1+/-6.2% (n=2) conjugation
      yields and its targeting properties to the same mAb labeled with [(125)I]SGMIB
      both in vitro and in vivo using U87MG.DeltaEGFR cells and xenografts were
      compared. In vitro paired-label internalization assays showed that the
      intracellular radioactivity from [(131)I]SIB-DOTA-L8A4 was 21.4+/-0.5% and 26.2+/
      1.1% of initially bound radioactivity at 16 and 24h, respectively. In comparison,
      these values for [(125)I]SGMIB-L8A4 were 16.7+/-0.5% and 14.9+/-1.1%. Similarly,
      the SIB-DOTA prosthetic group provided better tumor targeting in vivo than SGMIB
      over 8 d period. These results suggest that SIB-DOTA warrants further evaluation
      as a residualizing agent for labeling internalizing mAbs including those targeted
      to EGFRvIII.

PMID- 23159041
TI  - Contribution to investigation of antimicrobial activity of styrylquinolines.
AB  - Series of new ring-substituted styrylquinolines and two oxorhenium complexes were
      prepared and characterized. The compounds were analyzed using RP-HPLC to
      determine lipophilicity. Primary in vitro screening of the synthesized compounds
      was performed against fungal and bacterial strains. Some compounds were active
      against bacteria at micromolar level and against fungi at submicromolar level.
      Compounds 5,7-dichloro-2-[2-(2-ethoxyphenyl)vinyl]quinolin-8-ol expressed
      excellent antifungal activity comparable with or higher than the standard
      fluconazole as well as antibacterial activity against Staphylococcus strains
      comparable with or higher than the standards bacitracin, penicillin and
      ciprofloxacin. The structure-activity relationships are discussed.

PMID- 23159042
TI  - Dissecting T cell contraction in vivo using a genetically encoded reporter of
      apoptosis.
AB  - Contraction is a critical phase of immunity whereby the vast majority of effector
      T cells die by apoptosis, sparing a population of long-lived memory cells. Where,
      when, and why contraction occurs has been difficult to address directly due in
      large part to the rapid clearance of apoptotic T cells in vivo. To circumvent
      this issue, we introduced a genetically encoded reporter for caspase-3 activity
      into naive T cells to identify cells entering the contraction phase. Using two
      photon imaging, we found that caspase-3 activity in T cells was maximal at the
      peak of the response and was associated with loss of motility followed minutes
      later by cell death. We demonstrated that contraction is a widespread process
      occurring uniformly in all organs tested and targeting phenotypically diverse T
      cells. Importantly, we identified a critical window of time during which antigen
      encounters act to antagonize T cell apoptosis, supporting a causal link between
      antigen clearance and T cell contraction. Our results offer insight into a poorly
      explored phase of immunity and provide a versatile methodology to study apoptosis
      during the development or function of a variety of immune cells in vivo.

PMID- 23159043
TI  - Abeta amyloid, cognition, and APOE genotype in healthy older adults.
AB  - BACKGROUND: Only one study has investigated the relationship between cerebral
      beta-amyloid (Abeta), apolipoprotein E (APOE) epsilon4 genotype, and cognition.
      Although significant relationships between cerebral Abeta and cognition were
      observed in epsilon4 carriers but not noncarriers, the magnitude of this
      relationship was not reported. Further, when demographic variables were
      controlled, the influence of APOE epsilon4 on the relationship between cerebral
      Abeta and cognition dissipated. METHODS: In 144 healthy older adults who had
      undergone amyloid scanning and APOE epsilon4 genotyping in the Australian
      Imaging, Biomarkers, and Lifestyle (AIBL) Flagship Study of Ageing, correlations
      were conducted to determine the magnitude of relationship between cerebral Abeta
      and cognition in epsilon4 carriers and noncarriers. Fisher's Z was used to
      compare these correlations and Cohen's q determined the magnitude of difference
      between correlations. RESULTS: Cerebral Abeta was significantly associated with
      tasks of visual and verbal episodic memory in APOE epsilon4 carriers. This
      association was not observed in epsilon4 noncarriers. The relationship between
      cerebral Abeta and episodic memory in epsilon4 carriers was significantly
      different from that in epsilon4 noncarriers, and the magnitude of this difference
      was small to moderate. CONCLUSIONS: In APOE epsilon 4 carriers, there is a
      moderate negative relationship between cerebral Abeta and episodic memory. This
      suggests that increased cerebral Abeta may signify the onset of preclinical AD,
      especially in healthy older adults who are genetically at risk for AD.

PMID- 23159045
TI  - Short- versus long-term prediction of dementia among subjects with low and high
      educational levels.
AB  - BACKGROUND: Using simple measures of cognition and disability in a prospective
      community-living cohort of normal elderly persons, the main objectives of our
      study were to distinguish short- and long-term predictors for dementia according
      to educational level and to propose a tool for early detection of subjects at
      high risk of dementia. METHODS: Data derived from the French cohort study Paquid
      (Personnes Agees QUID), which included 3777 subjects, older than 65 years of age,
      who were followed for a 20-year period. The risk of dementia at 3 years and 10
      years was estimated by logistic regression for repeated measures combining data
      from all the 3- and 10-year windows throughout the follow-up. Predictors included
      disability assessed by the number of dependent items among four instrumental
      activities of daily living (IADLs), four neuropsychological tests, five Mini
      Mental State Examination (MMSE) subtests, and four items of subjective memory
      complaints. RESULTS: Of the 2882 included subjects, the number of IADLs remained
      a predictor of short- and long-term conversion to dementia for those with low
      educational level (combined with only one cognitive test) whereas the best
      predictors for more educated subjects combined subjective memory complaints and
      memory and executive function tests. The episodic memory subtest was the only
      predictive MMSE subtest. In the high-education-level group, the areas under the
      receiver-operating characteristic curve of the selected models were 0.85 for 3
      year prediction and 0.78 for 10-year prediction. CONCLUSION: Early predictors of
      dementia are different according to educational level. Among subjects reaching
      the secondary school level, early detection of those at high risk of dementia is
      possible with good predictive performance, with a few simple objective and
      subjective cognitive evaluations.

PMID- 23159044
TI  - Intracerebral propagation of Alzheimer's disease: strengthening evidence of a
      herpes simplex virus etiology.
AB  - BACKGROUND: A faulty human protein, abnormally phosphorylated tau, was recently
      publicized to spread "like a virus" from neuron to neuron in Alzheimer's
      patients' brains. For several decades, we have been amassing arguments showing
      that herpes simplex virus type 1 (HSV-1), not p-tau, propagates this
      interneuronal, transsynaptic pathologic cascade. METHODS: We reiterate convincing
      data from our own (and other) laboratories, reviewing the first anatomic foothold
      neurofibrillary tangles gain in brainstem and/or entorhinal cortex; the chronic
      immunosurveillance cellularity of the trigeminal ganglia wherein HSV-1 awakens
      from latency to reactivate; the inabilities of p-tau protein's physical
      properties to promote it to jump synapses; the amino acid homology between human
      p-tau and VP22, a key target for phosphorylation by HSV serine/threonine-protein
      kinase UL13; and the exosomic secretion of HSV-1-infected cells' L-particles,
      attesting to the cell-to-cell passage of microRNAs of herpesviruses. RESULTS: The
      now-maturing construct that reactivated HSV-1 best accounts for the intracerebral
      propagation of AD changes in the human brain should at last seem highly
      attractive. This hypothesis might even explain statins' apparent mechanism in
      some studies for lowering AD incidence. CONCLUSION: Provided that funding
      agencies will quickly ignite a new realm of investigation, the rejuvenated
      enthusiasm for testing this optimistic construct holds incalculable potential for
      rapid, efficacious clinical application, through already available and relatively
      safe antiviral therapeutics.

PMID- 23159046
TI  - Behavioral correlates of cerebrospinal fluid amino acid and biogenic amine
      neurotransmitter alterations in dementia.
AB  - BACKGROUND: Behavioral and psychological signs and symptoms of dementia (BPSD)
      are a heterogeneous group of behavioral and psychiatric disturbances occurring in
      dementia patients of any etiology. Research suggests that altered activities of
      dopaminergic, serotonergic, (nor)adrenergic, as well as amino acid
      neurotransmitter systems play a role in the etiopathogenesis of BPSD. In this
      study we attempted to identify cerebrospinal fluid (CSF) neurochemical correlates
      of BPSD to provide further insight into its underlying neurochemical
      pathophysiological mechanisms. METHODS: Patients with probable Alzheimer's
      disease (AD; n = 202), probable AD with cerebrovascular disease (n = 37),
      probable frontotemporal dementia (FTD; n = 32), and probable dementia with Lewy
      bodies (DLB; n = 26) underwent behavioral assessment and lumbar puncture. CSF
      levels of six amino acids and several biogenic amines and metabolites were
      analyzed using ultraperformance liquid chromatography with fluorescence detection
      and reversed-phase high-performance liquid chromatography with fluorescence
      detection. RESULTS: In the AD patients, CSF homovanillic acid/5
      hydroxyindoleacetic acid (HVA/5HIAA) ratios correlated positively with
      anxieties/phobias, whereas CSF levels of taurine correlated negatively with
      depression and behavioral disturbances in general. In FTD patients, CSF levels of
      glutamate correlated negatively with verbally agitated behavior. In DLB patients,
      CSF levels of HVA correlated negatively with hallucinations. CONCLUSIONS: Several
      neurotransmitter systems can be linked to one specific behavioral syndrome
      depending on the dementia subtype. In addition to biogenic amines and
      metabolites, amino acids seem to play a major role in the neurochemical etiology
      of BPSD as well.

PMID- 23159047
TI  - Biomarker evidence for uncoupling of amyloid build-up and toxicity in Alzheimer's
      disease.
AB  - Certain preparations of Alzheimer-associated amyloid beta (Abeta) exhibit rapid
      (within minutes) synaptotoxicity when applied to hippocampal slices or neuronal
      cell cultures, or when injected into the central nervous system of rodents. In
      addition, it is well known that some elderly people have brain amyloidosis
      without showing signs of cognitive impairment or neurodegeneration beyond the age
      norm. Biomarkers, reviewed extensively in a recent Perspectives article in
      Alzheimer's & Dementia, suggest that amyloid-positive individuals are at higher
      risk of Alzheimer's disease than similarly aged individuals without evidence of
      brain amyloidosis, provided they live long enough. But how can the brain resist
      amyloid pathology for many years? Here, we expand on recent biomarker studies
      suggesting that Abeta build-up and toxicity may occur in two phases. We
      hypothesize that the first phase may involve an autocatalytic build-up of a
      nontoxic Abeta reservoir, tentatively named the Abeta(Cat) pool, and that gain of
      toxicity may require brain incubation of Abeta in the water-deprived plaque
      milieu over years to produce modified forms of the protein that are truly
      neurotoxic (Abeta(Tox)). We argue for the need to describe the molecular natures
      of Abeta(Cat) and Abeta(Tox) in greater detail as a means to gain success in anti
      Abeta disease-modifying drug development. 

PMID- 23159048
TI  - Poliovirus evolution: the strong, silent type.
AB  - The high mutation rates of poliovirus and other RNA viruses promote viral
      diversity by rapid sampling of mutations. In this issue, Lauring et al. (2012)
      report that underlying synonymous codon variation in virus populations can have a
      considerable impact on adaptive potential with implications for viral fitness and
      virulence.

PMID- 23159049
TI  - M cell differentiation: distinct lineage or phenotypic transition? Salmonella
      provides answers.
AB  - Whether M cells arise from a distinct lineage or result from phenotypic
      transition is a matter of debate. In this issue of Cell Host & Microbe, Tahoun et
      al. (2012) provide evidence that SopB, a virulence factor of Salmonella enterica
      serovar Typhimurium, can induce phenotypic transition of lymphoid follicle
      associated enterocytes into M cells.

PMID- 23159050
TI  - Plasmodium protein export at higher PEXEL resolution.
AB  - Intraerythrocytic malaria parasites send hundreds of effector proteins into the
      host cell. Diverse modes of export have been proposed for different proteins. In
      this issue, Gruring et al. (2012) present findings that bring the models
      together.

PMID- 23159051
TI  - Defining a healthy human gut microbiome: current concepts, future directions, and
      clinical applications.
AB  - Indigenous microbiota are an essential component in the modern concept of human
      health, but the composition and functional characteristics of a healthy
      microbiome remain to be precisely defined. Patterns of microbial colonization
      associated with disease states have been documented, but the health-associated
      microbial patterns and their functional characteristics are less clear. A healthy
      microbiome, considered in the context of body habitat or body site, could be
      described in terms of ecologic stability (i.e., ability to resist community
      structure change under stress or to rapidly return to baseline following a stress
      related change), by an idealized (presumably health-associated) composition or by
      a desirable functional profile (including metabolic and trophic provisions to the
      host). Elucidation of the properties of healthy microbiota would provide a target
      for dietary interventions and/or microbial modifications aimed at sustaining
      health in generally healthy populations and improving the health of individuals
      exhibiting disrupted microbiota and associated diseases.

PMID- 23159052
TI  - Codon usage determines the mutational robustness, evolutionary capacity, and
      virulence of an RNA virus.
AB  - RNA viruses exist as dynamic and diverse populations shaped by constant mutation
      and selection. Yet little is known about how the mutant spectrum contributes to
      virus evolvability and pathogenesis. Because several codon choices are available
      for a given amino acid, a central question concerns whether viral sequences have
      evolved to optimize not only the protein coding consensus, but also the DNA/RNA
      sequences accessible through mutation. Here we directly test this hypothesis by
      comparing wild-type poliovirus to synthetic viruses carrying re-engineered capsid
      sequences with hundreds of synonymous mutations. Strikingly, such rewiring of the
      population's mutant network reduced its robustness and attenuated the virus in an
      animal model of infection. We conclude that the position of a virus in sequence
      space defines its mutant spectrum, evolutionary trajectory, and pathogenicity.
      This organizing principle for RNA virus populations confers tolerance to
      mutations and facilitates replication and spread within the dynamic host
      environment.

PMID- 23159053
TI  - Innate sensing of HIV-1 assembly by Tetherin induces NFkappaB-dependent
      proinflammatory responses.
AB  - Antiviral proteins that recognize pathogen-specific or aberrantly located
      molecular motifs are perfectly positioned to act as pattern-recognition receptors
      and signal to the immune system. Here we investigated whether the interferon
      induced viral restriction factor tetherin (CD317/BST2), which is known to inhibit
      HIV-1 particle release by physically tethering virions to the cell surface, has
      such a signaling role. We find that upon restriction of Vpu-defective HIV-1,
      tetherin acts as a virus sensor to induce NFkappaB-dependent proinflammatory gene
      expression. Signaling requires both tetherin's extracellular domain involved in
      virion retention and determinants in the cytoplasmic tail, including an endocytic
      motif, although signaling is independent of virion endocytosis. Furthermore,
      recruitment of the TNF-receptor-associated factor TRAF6 and activation of the
      mitogen-activated protein kinase TAK1 are critical for signaling. Human
      tetherin's ability to mediate efficient signaling may have arisen as a result of
      a five amino acid deletion that occurred in hominids after their divergence from
      chimpanzees.

PMID- 23159054
TI  - Salmonella transforms follicle-associated epithelial cells into M cells to
      promote intestinal invasion.
AB  - Salmonella Typhimurium specifically targets antigen-sampling microfold (M) cells
      to translocate across the gut epithelium. Although M cells represent a small
      proportion of the specialized follicular-associated epithelium (FAE) overlying
      mucosa-associated lymphoid tissues, their density increases during Salmonella
      infection, but the underlying molecular mechanism remains unclear. Using in vitro
      and in vivo infection models, we demonstrate that the S. Typhimurium type III
      effector protein SopB induces an epithelial-mesenchymal transition (EMT) of FAE
      enterocytes into M cells. This cellular transdifferentiation is a result of SopB
      dependent activation of Wnt/beta-catenin signaling leading to induction of both
      receptor activator of NF-kappaB ligand (RANKL) and its receptor RANK. The
      autocrine activation of RelB-expressing FAE enterocytes by RANKL/RANK induces the
      EMT-regulating transcription factor Slug that marks epithelial
      transdifferentiation into M cells. Thus, via the activity of a single secreted
      effector, S. Typhimurium transforms primed epithelial cells into M cells to
      promote host colonization and invasion.

PMID- 23159055
TI  - The Salmonella kinase SteC targets the MAP kinase MEK to regulate the host actin
      cytoskeleton.
AB  - After host cell entry, Salmonella replicate in membrane-bound compartments, which
      accumulate a dense meshwork of F-actin through the kinase activity of the
      Salmonella SPI-2 type III secretion effector SteC. We find that SteC promotes
      actin cytoskeleton reorganization by activating a signaling pathway involving the
      MAP kinases MEK and ERK, myosin light chain kinase (MLCK) and Myosin IIB.
      Specifically, SteC phosphorylates MEK directly on serine 200 (S200), a previously
      unstudied phosphorylation site. S200 phosphorylation is predicted to displace a
      negative regulatory helix causing autophosphorylation on the known MEK activatory
      residues, S218 and S222. In support of this, substitution of S200 with alanine
      prevented phosphorylation on S218 and S222, and phosphomimetic mutations of S200
      stimulated phosphorylation of these residues. Both steC-null and kinase-deficient
      mutant strains displayed enhanced replication in infected cells, suggesting that
      SteC manipulates the actin cytoskeleton to restrain bacterial growth, thereby
      regulating virulence.

PMID- 23159056
TI  - Mycobacterium tuberculosis-driven targeted recalibration of macrophage lipid
      homeostasis promotes the foamy phenotype.
AB  - Upon infection, Mycobacterium tuberculosis (Mtb) metabolically alters the
      macrophage to create a niche that is ideally suited to its persistent lifestyle.
      Infected macrophages acquire a "foamy" phenotype characterized by the
      accumulation of lipid bodies (LBs), which serve as both a source of nutrients and
      a secure niche for the bacterium. While the functional significance of the foamy
      phenotype is appreciated, the biochemical pathways mediating this process are
      understudied. We found that Mtb induces the foamy phenotype via targeted
      manipulation of host cellular metabolism to divert the glycolytic pathway toward
      ketone body synthesis. This dysregulation enabled feedback activation of the anti
      lipolytic G protein-coupled receptor GPR109A, leading to perturbations in lipid
      homeostasis and consequent accumulation of LBs in the macrophage. ESAT-6, a
      secreted Mtb virulence factor, mediates the enforcement of this feedback loop.
      Finally, we demonstrate that pharmacological targeting of pathways mediating this
      host-pathogen metabolic crosstalk provides a potential strategy for developing
      tuberculosis chemotherapy.

PMID- 23159057
TI  - Mitochondrial metabolism of glucose and glutamine is required for intracellular
      growth of Toxoplasma gondii.
AB  - Toxoplasma gondii proliferates within host cell vacuoles where the parasite
      relies on host carbon and nutrients for replication. To assess how T. gondii
      utilizes these resources, we mapped the carbon metabolism pathways in
      intracellular and egressed parasite stages. We determined that intracellular T.
      gondii stages actively catabolize host glucose via a canonical, oxidative
      tricarboxylic acid (TCA) cycle, a mitochondrial pathway in which organic
      molecules are broken down to generate energy. These stages also catabolize
      glutamine via the TCA cycle and an unanticipated gamma-aminobutyric acid (GABA)
      shunt, which generates GABA and additional molecules that enter the TCA cycle.
      Chemically inhibiting the TCA cycle completely prevents intracellular parasite
      replication. Parasites lacking the GABA shunt exhibit attenuated growth and are
      unable to sustain motility under nutrient-limited conditions, suggesting that
      GABA functions as a short-term energy reserve. Thus, T. gondii tachyzoites have
      metabolic flexibility that likely allows the parasite to infect diverse cell
      types.

PMID- 23159058
TI  - Metabolic adaptation to tissue iron overload confers tolerance to malaria.
AB  - Disease tolerance is a defense strategy that limits the fitness costs of
      infection irrespectively of pathogen burden. While restricting iron (Fe)
      availability to pathogens is perceived as a host defense strategy, the resulting
      tissue Fe overload can be cytotoxic and promote tissue damage to exacerbate
      disease severity. Examining this interplay during malaria, the disease caused by
      Plasmodium infection, we find that expression of the Fe sequestering protein
      ferritin H chain (FtH) in mice, and ferritin in humans, is associated with
      reduced tissue damage irrespectively of pathogen burden. FtH protection relies on
      its ferroxidase activity, which prevents labile Fe from sustaining proapoptotic c
      Jun N-terminal kinase (JNK) activation. FtH expression is inhibited by JNK
      activation, promoting tissue Fe overload, tissue damage, and malaria severity.
      Mimicking FtH's antioxidant effect or inhibiting JNK activation pharmacologically
      confers therapeutic tolerance to malaria in mice. Thus, FtH provides metabolic
      adaptation to tissue Fe overload, conferring tolerance to malaria.

PMID- 23159059
TI  - Lipocalin 2 bolsters innate and adaptive immune responses to blood-stage malaria
      infection by reinforcing host iron metabolism.
AB  - Plasmodium parasites multiply within host erythrocytes, which contain high levels
      of iron, and parasite egress from these cells results in iron release and host
      anemia. Although Plasmodium requires host iron for replication, how host iron
      homeostasis and responses to these fluxes affect Plasmodium infection are
      incompletely understood. We determined that Lipocalin 2 (Lcn2), a host protein
      that sequesters iron, is abundantly secreted during human (P. vivax) and mouse
      (P. yoeliiNL) blood-stage malaria infections and is essential to control P.
      yoeliiNL parasitemia, anemia, and host survival. During infection, Lcn2 bolsters
      both host macrophage function and granulocyte recruitment and limits
      reticulocytosis, or the expansion of immature erythrocytes, which are the
      preferred target cell of P. yoeliiNL. Additionally, a chronic iron imbalance due
      to Lcn2 deficiency results in impaired adaptive immune responses against
      Plasmodium parasites. Thus, Lcn2 exerts antiparasitic effects by maintaining iron
      homeostasis and promoting innate and adaptive immune responses.

PMID- 23159060
TI  - Uncovering common principles in protein export of malaria parasites.
AB  - For proliferation, the malaria parasite Plasmodium falciparum needs to modify the
      infected host cell extensively. To achieve this, the parasite exports proteins
      containing a Plasmodium export element (PEXEL) into the host cell.
      Phosphatidylinositol-3-phosphate binding and cleavage of the PEXEL are thought to
      mediate protein export. We show that these requirements can be bypassed, exposing
      a second level of export control in the N terminus generated after PEXEL cleavage
      that is sufficient to distinguish exported from nonexported proteins.
      Furthermore, this region also corresponds to the export domain of a second group
      of exported proteins lacking PEXELs (PNEPs), indicating shared export properties
      among different exported parasite proteins. Concordantly, export of both PNEPs
      and PEXEL proteins depends on unfolding, revealing translocation as a common step
      in export. However, translocation of transmembrane proteins occurs at the
      parasite plasma membrane, one step before translocation of soluble proteins,
      indicating unexpectedly complex translocation events at the parasite periphery.

PMID- 23159061
TI  - Semimembranosus release as the second step of soft tissue balancing in varus
      total knee arthroplasty.
AB  - There have been limited clinical data on the effect of semimembranosus release in
      patients with varus knees treated with total knee arthroplasty (TKA). The
      purposes of this study were to determine the effect of semimembranosus release
      and to evaluate the effectiveness of our release technique based on the three
      step algorithm which consisted of sequential release of 1) deep medial collateral
      ligament (MCL), 2) semimembranosus, 3) superficial MCL in 104 consecutive varus
      knees treated with TKA. Semimembranosus release had the desired effect on gap
      balancing in varus knees and our algorithmic medial release approach to the varus
      knee has shown to be favorable in correcting varus deformities during TKA.

PMID- 23159062
TI  - [Identification of alloantibodies and their associations: balance sheet of a year
      at the Auvergne-Loire French Blood Establishment].
AB  - OBJECTIVES: Some alloantibodies and their combinations can lead to delays or even
      an impasse in a transfusion, owing to the necessity of finding compatible red
      blood cell concentrates. The aim of this study was to determine the specificities
      of the most common alloantibodies, as well as the most common combinations of
      alloantibodies. METHODS AND MATERIALS: A retrospective study analysed erythrocyte
      alloantibodies identified in 2008 in the immunohematology laboratories at the
      Auvergne-Loire French Blood Establishment. The following data were studied:
      frequency, specificities of the alloantibodies, date of discovery, and patient
      age and sex. RESULTS: One thousand eight hundred and fifteen alloantibodies were
      identified in 1575 patients (median age: 63.5years, female/male ratio: 3.03). The
      most common alloantibodies were directed against the following antigens: RH3/E
      (18.7%), KEL1/K (17.3%), RH1/D (16.4%), MNS1/M (9.4%), FY1/Fya (6.9%), RH2/C
      (6.1%), KEL3/Kpa (4.7%), JK1/Jka (4.3%) and RH4/c (4.1%). In 13.1% of patients,
      at least two alloantibodies were identified. The pairs most frequently combined
      were anti-RH1/RH2, anti-RH3/RH4 and anti-RH3/KEL1. CONCLUSION: Specific
      associations of paired alloantibodies were identified. The main combinations
      provide indications on the choice of red cell concentrates in the inventory for a
      given patient. The data collected in our study show that when an antibody is
      identified, it is recommended for subsequent transfusion episodes to respect the
      phenotype RH 1-5 (D, C, E, c, e) and KEL1 (K) of the patient, and if possible
      antigens JK1 (Jka) and FY1 (Fya), and to a lesser extent MNS3 (S). Detailed
      knowledge of the immunological mechanisms leading to the formation of these
      alloantibodies and their combinations would allow better prevention of
      erythrocyte alloimmunization.

PMID- 23159063
TI  - Predictors of clinical remission following a first episode of non-affective
      psychosis: sociodemographics, premorbid and clinical variables.
AB  - The aim of the study was to identify predictors associated with a lower
      likelihood of achieving a clinical remission 1 year after the first break of the
      illness. Participants were 174 consecutive subjects included in a first episode
      programme with no prior treatment with antipsychotic medication. Patients were
      assigned to haloperidol, olanzapine or risperidone in a randomized, open-label,
      prospective clinical trial. The main outcome variable was the remission criteria
      developed by the Remission in Schizophrenia Working Group. Clinical variables
      were included in a logistic regression analysis in order to predict the remission
      state at 1 year. At 1 year, 31% of patients met criteria for remission. The
      logistic regression analysis revealed that the strongest predictors of achieving
      clinical remission 1 year away from a first episode of non-affective psychosis
      were the length of duration of untreated psychosis (DUP), the severity of
      negative symptomatology and the educational level attained at baseline. The
      results suggest that: (1) patients with a lengthy DUP, a greater severity of
      negative symptomatology at baseline and with a lower education level are in a
      higher risk of not achieving a clinical remission during the first year of
      treatment; and (2) early intervention clinical programs should aim to reduce the
      length of DUP in order to provide a better outcome for patients.

PMID- 23159064
TI  - Epithelial-mesenchymal transition, a novel target of sulforaphane via COX-2/MMP2,
      9/Snail, ZEB1 and miR-200c/ZEB1 pathways in human bladder cancer cells.
AB  - Metastasis and recurrence of bladder cancer are the main reasons for its poor
      prognosis and high mortality rates. Because of its biological activity and high
      metabolic accumulation in urine, sulforaphane, a phytochemical exclusively
      occurring in cruciferous vegetables, has a powerful and specific potential for
      preventing bladder cancer. In this paper, sulforaphane is shown to significantly
      suppress a variety of biochemical pathways including the attachment, invasion,
      migration and chemotaxis motion in malignant transitional bladder cancer T24
      cells. Transfection with cyclooxygenase-2 (COX-2) overexpression plasmid largely
      abolished inhibition of MMP2/9 expression as well as cell invasive capability by
      sulforaphane. Moreover, sulforaphane inhibited the epithelial-to-mesenchymal
      transition (EMT) process which underlies tumor cell invasion and migration
      mediated by E-cadherin induction through reducing transcriptional repressors,
      such as ZEB1 and Snail. Under conditions of over-expression of COX-2 and/or
      MMP2/9, sulforaphane was still able to induce E-cadherin or reduce Snail/ZEB1
      expression, suggesting that additional pathways might be involved. Further
      studies indicated that miR-200c played a role in the regulation of E-cadherin via
      the ZEB1 repressor but not by the Snail repressor. In conclusion, the EMT and two
      recognized signaling pathways (COX-2/MMP2,9/ ZEB1, Snail and miR-200c/ZEB1) are
      all targets for sulforaphane. This study indicated that sulforaphane may possess
      therapeutic potential in preventing recurrence of human bladder cancer.

PMID- 23159065
TI  - Kaempferol, a new nutrition-derived pan-inhibitor of human histone deacetylases.
AB  - Kaempferol is a natural polyphenol belonging to the group of flavonoids.
      Different biological functions like inhibition of oxidative stress in plants or
      animal cells and apoptosis induction have been directly associated with
      kaempferol. The underlying mechanisms are only partially understood. Here we
      report for the first time that kaempferol has a distinct epigenetic activity by
      inhibition of histone deacetylases (HDACs). In silico docking analysis revealed
      that it fits into the binding pocket of HDAC2, 4, 7 or 8 and thereby binds to the
      zinc ion of the catalytic center. Further in vitro profiling of all conserved
      human HDACs of class I, II and IV showed that kaempferol inhibited all tested
      HDACs. In clinical oncology, HDAC inhibitors are currently under investigation as
      new anticancer compounds. Therefore, we studied the effect of kaempferol on human
      derived hepatoma cell lines HepG2 and Hep3B as well as on HCT-116 colon cancer
      cells and found that it induces hyperacetylation of histone complex H3.
      Furthermore, kaempferol mediated a prominent reduction of cell viability and
      proliferation rate. Interestingly, toxicity assays revealed signs of relevant
      cellular toxicity in primary human hepatocytes only starting at 50 MUM as well as
      in an in vivo chicken embryotoxicity assay at 200 MUM. In conclusion, the
      identification of a novel broad inhibitory capacity of the natural compound
      kaempferol for human-derived HDAC enzymes opens up the perspective for clinical
      application in both tumor prevention and therapy. Moreover, kaempferol may serve
      as a novel lead structure for chemical optimization of pharmacokinetics,
      pharmacology or inhibitory activities.

PMID- 23159066
TI  - Treatment with n-3 polyunsaturated fatty acids reverses endothelial dysfunction
      and oxidative stress in experimental menopause.
AB  - Menopause is associated with endothelial dysfunction and oxidative stress. In
      this condition, reduced n-3 polyunsaturated fatty acids (n-3 PUFAs) contribute to
      cardiovascular disease. We investigated whether treatment with n-3 PUFA reverses
      endothelial dysfunction and oxidative stress in experimental menopause. Thirty
      female rats underwent either sham-surgery or bilateral ovariectomy or bilateral
      ovariectomy+oral n-3 PUFA (0.8 g kg(-1) day(-1) for 2 months). Ovariectomy caused
      endothelial dysfunction to acetylcholine, which was reversed by superoxide
      scavenger Tiron. Erythrocyte membrane lipid composition was characterized by
      reduced n-3 PUFA total content and omega-3 index, and by concomitant increase in
      n-6:n-3 PUFA ratio. Ovariectomy-related oxidative stress, demonstrated by both
      enhanced superoxide production and 3-nitrotyrosine expression in aorta, was
      associated with increased nicotinamide adenine dinucleotide phosphate (NADPH)
      oxidase subunit NOX-4 protein expression. Endothelial nitric oxide synthase
      (eNOS) functional inhibition by l-NG-nitroarginine methyl ester, protein
      expression and activity did not change. In ovariectomized rats, treatment with n
      3 PUFA increased n-3 PUFA total content and omega-3 index and decreased n-6:n-3
      PUFA ratio in erythrocyte membrane, reversed vascular oxidative stress,
      endothelial dysfunction, aortic 3-nitrotyrosine and markedly lowered NOX-4
      protein expression; eNOS protein expression also increased, paralleled by
      reversal of inhibitory binding to Caveolin-1, while ex-vivo functional inhibition
      and NOS synthesis were unchanged. These findings demonstrate in vivo a
      therapeutic benefit of n-3 PUFA on menopause-associated endothelial dysfunction
      by reversal of alterations in membrane lipid composition induced by ovariectomy
      and by reduction of vascular oxidative stress. In this setting they also identify
      NOX-4 as a potential target to reduce oxidative stress-mediated vascular
      complications.

PMID- 23159067
TI  - Chiral signature of venlafaxine as a marker of biological attenuation processes.
AB  - The chiral signature of the antidepressant venlafaxine was used in this study to
      gain insight into biological attenuation processes and to differentiate abiotic
      and biotic transformation processes in water. Laboratory scale experiments
      revealed that sorption and phototransformation processes were not
      enantioselective while venlafaxine was enantioselectively biotransformed into O
      desmethylvenlafaxine. The enantiomeric fraction (EF) variations of venlafaxine
      appeared to be proportional to its microbial fractional conversion.
      Enantioselective biotransformation of venlafaxine was also investigated in a
      eutrophic French river. Venlafaxine was found to be racemic at the output of the
      main wastewater treatment plant discharging into the river, independently of the
      sampling date during the year. An analysis of EF variations might provide
      evidence of biodegradation along a 30 km river stretch.

PMID- 23159068
TI  - Influence of competing inorganic cations on the ion exchange equilibrium of the
      monovalent organic cation metoprolol on natural sediment.
AB  - The aim of this study was to systematically investigate the influence of the mono
      and divalent inorganic ions Na(+) and Ca(2+) on the sorption behavior of the
      monovalent organic cation metoprolol on a natural sandy sediment at pH=7.
      Isotherms for the beta-blocker metoprolol were obtained by sediment-water batch
      tests over a wide concentration range (1-100000 MUg L(-1)). Concentrations of the
      competing inorganic ions were varied within freshwater relevant ranges. Data
      fitted well with the Freundlich sorption model and resulted in very similar
      Freundlich exponents (n=0.9), indicating slightly non-linear behavior. Results
      show that the influence of Ca(2+) compared to Na(+) is more pronounced. A
      logarithmic correlation between the Freundlich coefficient K(Fr) and the
      concentration or activity of the competing inorganic ions was found allowing the
      prediction of metoprolol sorption on the investigated sediment at different
      electrolyte concentrations. Additionally, the organic carbon of the sediment was
      completely removed for investigating the influence of organic matter on the
      sorption of metoprolol. The comparison between the experiments with and without
      organic carbon removal revealed no significant contribution of the organic carbon
      fraction (0.1%) to the sorption of metoprolol on the in this study investigated
      sediment. Results of this study will contribute to the development of predictive
      models for the transport of organic cations in the subsurface.

PMID- 23159069
TI  - Degradation of lidocaine, tramadol, venlafaxine and the metabolites O
      desmethyltramadol and O-desmethylvenlafaxine in surface waters.
AB  - The photodegradation and biotic transformation of the pharmaceuticals lidocaine
      (LDC), tramadol (TRA) and venlafaxine (VEN), and of the metabolites O
      desmethyltramadol (ODT) and O-desmethylvenlafaxine (ODV) in the aquatic
      environmental have been investigated. Photodegradation experiments were carried
      out using a medium pressure Hg lamp (laboratory experiments) and natural sunlight
      (field experiments). Degradation of the target compounds followed a first-order
      kinetic model. Rates of direct photodegradation (light absorption by the
      compounds itself) at pH 6.9 were very low for all of the target analytes
      (<=0.0059 h(-1) using a Hg lamp and <=0.0027 h(-1) using natural sunlight), while
      rates of indirect photodegradation (degradation of the compounds through
      photosensitizers) in river water at pH 7.5 were approximately 59 (LDC), 5 (TRA),
      8 (VEN), 15 (ODT) and 13 times (ODV) higher than the rates obtained from the
      experiments in ultrapure water. The accelerated photodegradation of the target
      compounds in natural water is attributed mainly to the formation of hydroxyl
      radicals through photochemical reactions. Biotic (microbial) degradation of the
      target compounds in surface water has been shown to occur at very low rates
      (<=0.00029 h(-1)). The half-life times determined from the field experiments were
      31 (LDC), 73 (TRA), 51 (VEN), 21 (ODT) and 18h (ODV) considering all possible
      mechanisms of degradation for the target compounds in river water (direct
      photodegradation, indirect photodegradation and biotic degradation).

PMID- 23159070
TI  - The effects of antibiotic cocktails at environmentally relevant concentrations on
      the community composition and acetate biodegradation kinetics of bacterial
      biofilms.
AB  - Antibiotics and antibacterials are present in water bodies worldwide but little
      is known about their effects on the biological processes often used to treat
      water. In this research, the effect of antibiotics on bacterial activity and
      community structure was investigated by growing biofilms in the presence and
      absence of a mixture of three compounds (sulfamethoxazole, erythromycin, and
      ciprofloxacin) in a continuous-flow rotating annular bioreactor fed acetate as a
      carbon and energy source. Steady-state, surface area-normalized substrate
      utilization rates for all antibiotic treatments (all at 0.33 MUg L(-1), all at
      3.33 MUg L(-1), and 1 at 3.33 MUg L(-1) with the other 2 at 0.33 MUg L(-1)) were
      similar to the control experiments. Higher attached biomass levels in the
      experiments with ciprofloxacin at 3.33 MUg L(-1) resulted in lower steady-state
      biomass-normalized substrate utilization rates in comparison to other runs.
      Microbial community analyses via automated ribosomal intergenic spacer analysis
      revealed significant shifts in community structure for the experiments dosed with
      the highest concentrations of ciprofloxacin, suggesting that the antibiotic
      selected for more resistant bacterial strains. The results of this research also
      suggest that mixtures of antibiotics at the sub-MUg L(-1) concentrations
      typically observed in surface waters are unlikely to affect biological process
      performance, at least in terms of the degradation of easily assimilable
      compounds. Conversely, changes to community structure and biofilm quantity might
      be expected with ciprofloxacin at MUg L(-1) concentrations.

PMID- 23159071
TI  - Spatial distribution of organochlorine pesticides (OCPs) and effect of soil
      characters: a case study of a pesticide producing factory.
AB  - The distribution and concentration of some organochlorine pesticides (OCPs) in
      the soil around a pesticide factory in Zibo, China, were examined, including
      dichlorodiphenyltrichloroethane (DDT) and its metabolites, isomers of
      hexachlorocyclohexane (HCH) and endosulfan (ENDO). The results showed that the
      OCPs concentrations were extraordinary high in this region. The concentrations of
      DDTs, HCHs, and ENDO were measured in the range of 0.775-226.711, 0.248-42.838,
      and 0.081-1.644 mg kg(-1), respectively. DDT and its isomers were identified to
      be the dominate contaminants in most of the sampling sites. In the vertical
      direction, the distribution pattern of the total OCPs was in order of DDTs, HCHs,
      and ENDO in the 0-20 cm, but in 20-40 and 40-60 cm the trends were unobvious.
      Although no recent input occurred in most areas, the residues of OCPs remained in
      deep soil due to their persistence. Unlike ENDO, DDTs and HCHs appeared to have
      the similar property in terms of not only the migration pattern in soil, but also
      the relationship to the same dominant impact factor (i.e. organic matter). DDTs
      and HCHs were affected positively by the organic matter, whereas ENDO was
      affected negatively. Due to the interrelationship among various impact factors,
      the spatial distribution of pesticides in the soil was considered to be a
      combined result.

PMID- 23159072
TI  - Phytomanagement of strongly acidic, saline eutrophic wetlands polluted by mine
      wastes: the influence of liming and Sarcocornia fruticosa on metals mobility.
AB  - The aim of this study was to assess the effectiveness of combining liming and
      vegetation for the phytomanagement of strongly acidic, saline eutrophic wetlands
      polluted by mine wastes. Simulated soil profiles were constructed and four
      treatments were assayed: without liming+without plant, without liming+with plant,
      with liming+without plant and with liming+with plant. The plant species was the
      halophyte Sarcocornia fruticosa. Three horizons were differentiated: A (never
      under water), C1 (alternating flooding-drying conditions) and C2 (always under
      water). The soluble Cd, Cu, Mn, Pb and Zn concentrations were measured regularly
      for 18 weeks and a sequential extraction procedure was applied at the end of the
      experiment. Liming was effective (between ~70% and ~100%) in reducing the soluble
      Zn, Cu and Pb. In contrast, soluble Mn and Cd increased with liming, especially
      in the treatment with liming+with plant, where the concentrations were 2-fold
      higher than in the non-limed treatments. The amendment increased the contents of
      Zn, Mn and Cd bound to potentially-mobilisable soil fractions at the expense of
      the most-environmentally-inert fractions. Hence, the combined use of liming and
      vegetation may increase the long-term environmental risk of metals
      solubilisation.

PMID- 23159073
TI  - A qualitative study exploring the impact of student nurses working part time as a
      health care assistant.
AB  - BACKGROUND: National and international evidence indicates that university
      students engage in employment whilst studying. Research has suggested that
      nursing students either enter training with previous care experience or tend to
      work part time in a health related area whilst undertaking higher education. The
      impact of this on the socialisation process remains unclear. OBJECTIVES: Based on
      the symbolic interactionist framework, this paper reports on a theme from a large
      mixed methods study - the extent and implications of student nurses' work
      experience on learning and training. DESIGN: One qualitative stage from a
      sequential exploratory mixed methods design. SETTINGS: One higher education
      institution in the United Kingdom. PARTICIPANTS: Forty-five pre-registration
      nursing students. METHODS: Thirty-two students took part in four focus groups and
      13 took part in individual interviews. RESULTS: Findings revealed that 27 (60%)
      of students were in paid nursing related employment. This was reported to be
      advantageous by most participants with regards to enhancing confidence, skills
      and time spent in the clinical setting. However, it was also perceived by a small
      number of participants as being detrimental to subsequent learning resulting in
      role confusion, influencing placement behaviour, and preferences for future
      nursing practice. Student participants with no prior work experience believed
      this placed them at a disadvantage, negatively influencing their learning,
      ability to fit in, and adjustment on placement. Findings have suggested that
      student participants desire more recognition of the experience and skills they
      have gained from their employment. CONCLUSIONS: Whilst care experience among the
      student nursing population is advocated, the results of this study show that it
      is perceived to impinged on their learning and educational journey. Policy
      makers, educationalists and health service providers need to be aware of the
      students who operate within the dual roles of student and health care worker so
      as to provide guidance and appropriate direction.

PMID- 23159074
TI  - [Stereotactic radiotherapy for early non-small cell lung cancer].

PMID- 23159075
TI  - [Arsenic trioxide restores ERalpha expression in ERalpha-negative human breast
      cancer cells and its treatment efficacy in combination with tamoxifen in
      xenografts in nude mice].
AB  - OBJECTIVE: To study the demethylation effect of arsenic trioxide (As2O3) on
      ERalpha-negative human breast cancer MDA-MB-435s cells and its possible
      mechanisms, and to observe its treatment efficacy in combination with tamoxifen
      (TAM) after ERalpha re-expression. METHODS: MTT assay was used to examine the
      inhibitory effect of As2O3 treatment alone or in combination with TAM on cell
      proliferation. A nude mouse xenograft model was used to further examine the
      treatment efficacy in vivo. MSP was used to detect the methylation status of
      ERalpha gene after treated with As2O3 in MDA-MB-435s cells and the transplanted
      tumor tissues. RT-PCR was used to detect the mRNA expression of DNMT1 and
      Eralpha. Western bolt was used to detect the DNMT1 and ERalpha protein
      expression. The diameter of xenograft tumors was measured weekly, and the tumor
      growth curve was drawn. RESULTS: The level of proliferation of the MDA-MB-435s
      cells was significantly suppressed after treatment with different concentration
      of As2O3 alone or As2O3 combined with TAM, and the 4 umol/L As2O3 + TAM treatment
      for 72 h showed the highest inhibition rate (62.6%). 1, 2, 4 umol/L As2O3 had
      demethylation effect on MDA-MB-435s cells, and the DNMT1 mRNA and protein
      expression was inhibited and accompanied by ERalpha mRNA and protein re
      expression. The unmethylation specific bands of ERalpha gene were enhanced after
      treated by As2O3 alone or As2O3 combined with TAM in the xenograft tumors. The
      expression of DNMT1 mRNA and protein was inhibited, and accompanied by ERalpha
      mRNA and protein re-expression. An significant decrease of volume and weight of
      the xenograft tumors in the As2O3 treated alone or combined with TAM groups was
      observed compared with those of the normal saline group or TAM alone group (P <
      0.05), and the 4 mg/kg As2O3 + TAM group had the highest inhibition rate of tumor
      weight (79.5%) and volume (76.4%). CONCLUSIONS: ERalpha can be re-expressed in
      ERalpha-negative breast cancer MDA-MB-435s cells after treated with As2O3 by
      inhibiting the DNMT1 activity. MDA-MB-435s cells are re-sensitized to endocrine
      therapy after ERalpha re-expression. As2O3 combined with TAM may provide a new
      therapeutic approach for patients with ERalpha-negative breast cancer in the
      clinic.

PMID- 23159076
TI  - [Influence of rosiglitazone and all-trans-retinoic acid on angiogenesis and
      growth of myeloma xenograft in nude mice].
AB  - OBJECTIVE: To observe the effect of rosiglitazone (RGZ) and all-trans-retinoic
      acid (ATRA) on the growth of myeloma xenograft in nude mice and to explore the
      influence of RGZ and ATRA on VEGF expression and angiogenesis in the tumor.
      METHODS: VEGF gene expression in myeloma cell line U266 cells was analyzed by
      semi-quantitative RT-PCR after incubation with RGZ, ATRA, or RGZ + ATRA for 24 h.
      Myeloma xenograft was established by subcutaneous injection of 10(7) U266 cells
      in the scapula area of 4-week old nude mice. 7 days later, the nude mice were
      administered with RGZ, ATRA or RGZ + ATRA, respectively, by intraperitoneal
      injection once every day for 21 days. The control mice were given equal volume of
      normal saline instead of the drug. On the 21(st) day of treatment, the mice were
      sacrificed and the tumors were taken off, and the tumor volume and weight were
      measured. The tumors were examined by histopathology with HE staining, and
      microvessel density (MVD), CD34 and VEGF expression in the tumors were analyzed
      by immunohistochemical staining. RESULTS: VEGF mRNA was highly expressed in U266
      cells and was decreased in a dose-dependent manner after incubation with RGZ. The
      VEGF mRNA level was further more decreased after RGZ + ATRA treatment. Xenografts
      of U266 cells were developed in all nude mice. The volume and weight of
      xenografts in the RGZ group were (785 +/- 262) mm(3) and (1748 +/- 365) mg,
      respectively, significantly lower than those of the control group (both P <
      0.01). More significant inhibition was in the RGZ + ATRA group, (154 +/- 89)
      mm(3) and (626 +/- 102) mg, respectively, both were P < 0.05 vs. the RGZ group.
      RGZ inhibited the angiogenesis in U266 xenografts and immunohistochemical
      staining showed that the tumor MVD and VEGF expression were significantly
      decreased by RGZ treatment, and further more inhibited in the RGZ + ATRA group.
      VEGF protein was expressed in all xenografts in the nude mice. Its
      immunohistochemical staining intensity was 2.20 +/- 0.40 in the control group,
      significantly higher than that of 1.48 +/- 0.37 in the RGZ group (P < 0.01), and
      that of RGZ + ATRA group was 0.58 +/- 0.26, further significantly lower than that
      of the RGZ group (P < 0.01). CD34 was expressed in all xenografts, most highly in
      the control group and lowest in the RGZ + ATRA group. The microvessel density
      (MVD) was highest in the control group (56.4 +/- 15.2), significantly lower in
      the RGZ group (44.6 +/- 11.2) (P < 0.05), and lowest in the RGZ + ATRA group
      (21.5 +/- 8.6, P < 0.01). CONCLUSIONS: The growth of myeloma cells can also be
      inhibited by RGZ and ATRA in nude mice in vivo. In addition to differentiation
      and apoptosis induction, RGZ can inhibit the formation of myeloma xenograft
      probably also through the downregulation of VEGF expression and subsequent
      angiogenesis.

PMID- 23159077
TI  - [Effects of 5-Aza-2-deoxycytidine on DNA methylation of anti-oncogenes in non
      small cell lung cancer cells].
AB  - OBJECTIVE: To observe the expression of SFRP1 gene methylation in non-small cell
      lung cancer (NSCLC), and study the effect of 5-Aza-2-deoxycytidine (5-Aza-CdR) on
      DNA methylation and expression of SFRP1, p16 and MGMT genes in the human lung
      cancer cell line SPC-A-1 cells. METHODS: SP immunohistochemistry and methylation
      specific PCR were used to detect the SFRP1 methylation in 60 NSCLC cases, and 21
      cases of benign lung diseases were used as control group. SPC-A-1 cells were
      cultured and treated with 5-Aza-CdR. The promoter methylation status of SFRP1,
      p16 and MGMT genes were detected by methylation-specific polymerase (MSP) chain
      reaction, and mRNAs were detected by real-time PCR. RESULTS: The positive rate of
      SFRP1 gene methylation in NSCLC was significantly higher than that in normal lung
      tissue (58.3% vs. 14.3%; chi(2) = 12.118, P = 0.001). SFRP1 gene methylation was
      closely correlated with lymph node metastasis and degree of differentiation in
      NSCLC (P < 0.05). SFRP1 protein expression was correlated with clinical stage,
      degree of differentiation and lymph node metastasis in NSCLC (P < 0.05). The
      positive expression of SFRP1 protein in 30 cases of NSCLC tissue containing SFRP1
      gene methylation was significantly higher than that in non-methylated NSCLC
      (68.6% vs. 24.0%; chi(2) = 9.613, P = 0.002). SFRP1 gene methylation was closely
      correlated with SFRP1 gene protein expression in NSCLC (P < 0.05). Negative
      expression of SFRP1 protein was correlated with the differentiation, clinical
      stage, and lymph node metastasis in NSCLC (all P < 0.05). Without 5-Aza-CdR
      treatment, the expressions of methylation of SFRP1, p16 and MGMT genes and their
      mRNA were low. After 5-Aza-CdR treatment at different concentrations, their
      expressions were significantly elevated (all P < 0.05). CONCLUSIONS: SFRP1 gene
      methylation is closely associated with carcinogenesis and development of NSCLC. 5
      Aza-CdR may reverse the methylation of SFRP1, p16 and MGMT genes, and facilitate
      the re-expression of the anti-oncogenes.

PMID- 23159078
TI  - [Single nucleotide polymorphism in flanking region of miR-30c influences the
      maturing process of miR-30c in lung carcinoma].
AB  - OBJECTIVE: To investigate the effect of a common polymorphism rs928508(A/G) in
      flanking region of miR-30c on the expression of pri, pre and mature miR-30c, and
      discuss the effect of this polymorphism on the maturing process of miR-30c in
      lung carcinoma. METHODS: The pGL3-promoter-miR-30c-A and pGL3-promoter-miR-30c-G
      luciferase plasmids were created containing A or G allele of miR-30c flanking
      region. Taqman assay was used to genotype rs928508 polymorphism in 50 lung cancer
      tissues. RT-PCR was performed to determine the expression of pri-miR-30c, pre-miR
      30c, mature miR-30c and miR-30c host gene NFYC in the 50 lung cancer tissues.
      RESULTS: The luciferase expression level of the pGL3-promoter-miR-30c-A construct
      group was not significantly different compared with that in the the pGL3-promoter
      miR-30c-G construct group (A549 cells, P = 0.758; 293A cells, P = 0.554; CHO
      cells, P = 0.175). The results demonstrated that rs928508(A/G) variant had no
      effect on the transcriptional regulation of pri-miR-30c. In the genotype
      phenotype collection analysis of the 50 lung cancer tissues, the expression of
      pre-miR-30c and mature miR-30c for rs928508 AG/GG genotypes showed significantly
      lower levels compared with those in the AA genotype (P = 0.009, P = 0.011).
      However, the expression of pri-miR-30c showed no significant difference between
      AG/GG genotypes and AA genotype. Similarly, the expression of host NFYC gene was
      correlated with pri-miR-30c, showed no significant difference between AG/GG
      genotypes and AA genotype. CONCLUSION: The rs928508(A/G) polymorphism in flanking
      region of miR-30c could influence the processing from pri-miR-30c to mature miR
      30c, but does not influence the transcription of pri-miR-30c.

PMID- 23159079
TI  - [Value of CK20 immunocytochemistry as an adjuvant to urine liquid-based cytology
      in detection of urothelial carcinoma].
AB  - OBJECTIVE: To investigate the value of cytokeratin 20 (CK20) immunocytochemical
      (ICC) detection in the urine liquid-based cytological specimens in diagnosis of
      urothelial carcinoma (UC). METHODS: The study consisted of prospective and
      retrospective groups. In the prospective group, voided urine samples were
      collected from patients with a variety of urological conditions and healthy
      individuals. Urine cytological diagnosis and CK20 ICC were performed on the
      collected specimens. In the retrospective group, archived urine slides with
      cytological diagnoses of atypical urothelial cells (AUC), suspicious carcinoma
      (SuCA) and carcinoma (CA) were selected. Then they were re-stained
      immunocytochemically with monoclonal antibody against CK20 after decolorization.
      Histological diagnosis and clinical follow-up result were used as the gold
      standard for analysis. RESULTS: There were 136 cases in the prospective group,
      including 89 cases of UC, 19 cases of other urogenital malignancies, 12 cases of
      benign lesions and 16 cases of normal control. The sensitivity of CK20 ICC in
      detection of UC was 75.3%, significantly higher than that of LBC (48.3%, P <
      0.001). The positive rate of CK20 was 64.7% (22/34) in G1 UC, 73.3% (22/30) in G2
      UC, and 91.3% (21/23) in G3 UC (P < 0.001). The specificity of CK20 ICC was
      91.5%, the same as that of LBC. There were 163 cases in retrospective group,
      including 119 cases of UC, 17 cases of other urogenital malignancies and 27 cases
      of benign lesions. The cytological diagnoses of them were 68 cases of CA, 47
      cases of SuCA and 48 cases of AUC. The positive rates of CK20 ICC in UC and non
      UC (other urogenital malignancies and benign lesions) cases were 90.8% and 15.9%,
      respectively, with a statistically very significant difference (P < 0.001). The
      LBC of all the 119 cases of UC included 62 (52.1%) cases of CA, 35 (29.4%) cases
      of SuCA and 22 (18.5%) cases of AUC. The positive rates of CK20 in the LBC
      diagnosed CA, SuCA and AUC were 96.8%, 97.1% and 63.6%, respectively. The LBC of
      all the 44 non-UC cases included 6 (13.6%) cases of CA, 12 (27.3%) cases of SuCA
      and 26 (59.1%) cases of AUC, and the positive rates of CK20 in the LBC-diagnosed
      CA, SuCA and AUC were 33.3%, 33.3% and 3.8%, respectively. The differences of UC
      and non-UC cases between the corresponding categories of LBC were significant (P
      < 0.0001, respectively). CONCLUSION: CK20 immunocytochemistry as an auxiliary
      method to urine liquid-based cytology can increase the sensitivity in detection
      of urothelial carcinomas.

PMID- 23159080
TI  - [Expression of Wnt5a, APC, beta-catenin and their clinical significance in human
      colorectal adenocarcinoma].
AB  - OBJECTIVE: To study the expression of Wnt5a gene mRNA and Wnt5a, APC, beta
      catenin proteins in human colorectal adenocarcinoma (CRC) and explore its
      clinical significance. METHODS: Wnt5a mRNA level was measured in 30 patients with
      CRC and paired non-tumor tissues by real-time PCR. Immunohistochemical staining
      of Wnt5a, APC, beta-catenin was performed in samples of 62 patients with CRC
      using SP system. RESULTS: The relative expression level of Wnt5a mRNA in fresh
      CRC is 0.1232 +/- 0.0140, which is significantly higher than that in adjacent
      colorectal mucosa (0.0497 +/- 0.0074, P = 0.02). A low expression of Wnt5a
      protein was observed in 38 of 62 CRC. Wnt5a protein expression was closely
      correlated with the tumor types and the degree of tumor differentiation (P <
      0.05). There was no apparent relationship with lymph node metastasis, depth of
      myometrial invasion and TNM stages (P > 0.05). APC protein was decreased in 38 of
      62 CRC. The expression of APC was closely correlated with the tumor types (P <
      0.05). There was no apparent relationship with the degree of tumor
      differentiation, lymph node metastasis, depth of myometrial invasion and TNM
      stages (P > 0.05). The expression of beta-catenin was observed in cytoplasm
      and/or cell nuclei in 50 of 62 CRC. The positive rate of beta-catenin expression
      was closely correlated with the degree of tumor differentiation, lymph node
      metastasis, depth of myometrial invasion and TNM stages (P < 0.05). There was no
      apparent relationship with the tumor types (P > 0.05). The expressions of Wnt5a
      (r = 0.271, P = 0.027) and APC (r = 0.343, P = 0.004) were correlated with that
      of beta-catenin in CRC, respectively, but there was no correlation between the
      expressions of Wnt5a and APC protein (r = 0.218, P = 0.078) in the tumors.
      CONCLUSIONS: Wnt5a, APC and beta-catenin genes might be involved in the
      carcinogenesis and development of CRC. It is hypothesized that down-regulation of
      APC and Wnt5a proteins may be one of causes of ectopic expression of beta-catenin
      in CRC.

PMID- 23159081
TI  - [Measurement of intrafraction displacement of the mediastinal metastatic lymph
      nodes of non-small cell lung cancer based on four-dimensional computed tomography
      (4D-CT)].
AB  - OBJECTIVE: To measure the intrafraction displacement of the mediastinal
      metastatic lymph nodes of non-small cell lung cancer (NSCLC) based on four
      dimensional computed tomography (4D-CT), and to provide the basis for the
      internal margin of metastatic mediastinal lymph nodes. METHODS: Twenty-four NSCLC
      patients with mediastinal metastatic lymph nodes confirmed by contrast enhanced
      CT (short axis diameter >= 1 cm) were included in this study. 4D-CT simulation
      was carried out during free breathing and 10 image sets were acquired. The
      mediastinal metastatic lymph nodes and the dome of ipsilateral diaphragma were
      separately delineated on the CT images of 10 phases of breath cycle, and the
      lymph nodes were grouped as the upper, middle and lower mediastinal groups
      depending on the mediastinal station. Then the displacements of the lymph nodes
      in the left-right, anterior-posterior, superior-inferior directions and the 3
      dimensional vector were measured. The differences of displacement in three
      directions for the same group of metastatic lymph nodes and in the same direction
      for different groups of metastatic lymph nodes were compared. The correlation
      between the displacement of ipsilateral diaphragma and mediastinal lymph nodes
      was analyzed in superior-inferior direction. RESULTS: The displacements in left
      right, anterior-posterior and superior-inferior directions were (2.24 +/- 1.55)
      mm, (1.87 +/- 0.92) mm and (3.28 +/- 2.59) mm for the total (53) mediastinal
      lymph nodes, respectively. The vectors were (4.70 +/- 2.66) mm, (3.87 +/- 2.45)
      mm, (4.97 +/- 2.75) mm and (5.23 +/- 2.67) mm for the total, upper, middle and
      lower mediastinal lymph nodes, respectively. For the upper mediastinal lymph
      nodes, the displacements in left-right, anterior-posterior and superior-inferior
      directions showed no significant difference between each other (P > 0.05). For
      the middle mediastinal lymph nodes, the displacements merely in anterior
      posterior and superior-inferior directions showed significant difference (P =
      0.005), while the displacements were not significantly different in the left
      right and anterior-posterior, left-right and superior-inferior directions (P >
      0.05). The displacements of the total and the lower mediastinal lymph nodes in
      left-right and superior-inferior, or anterior-posterior and superior-inferior
      directions were significantly different (P < 0.05), but was not significantly
      different in left-right and anterior-posterior directions (P > 0.05). The
      displacements of different group of mediastinal lymph nodes in a single direction
      or vector showed no significant difference (P > 0.05). In the superior-inferior
      direction, the correlation between the displacements of ipsilateral diaphragma
      and mediastinal lymph nodes were not statistically significant (P > 0.05).
      CONCLUSIONS: During free breathing, the differences between the intrafractional
      displacement of mediastinal metastatic lymph nodes in the same direction and its
      station were not statistically significant. The displacements of the total
      mediastinal metastatic lymph nodes in the superior-inferior direction were
      greater than that in the left-right and anterior-posterior directions, especially
      for the middle and lower mediastinal metastatic lymph nodes. There was no
      significant correlation between the displacements of ipsilateral diaphragma and
      the mediastinal metastatic lymph nodes in the superior-inferior direction, so it
      was unreasonable to estimate and predict the displacement of mediastinal
      metastatic lymph nodes by the displacement of ipsilateral diaphragma.

PMID- 23159082
TI  - [Relationship of gross tumor volume with lymph node metastasis and prognosis of
      esophageal carcinoma].
AB  - OBJECTIVE: To explore whether there is a relationship between gross tumor volume
      (GTV) and pathologic lymph node metastasis or prognosis of esophageal carcinoma,
      and to provide a new prognosis reference for esophageal carcinoma (EC). METHODS:
      Six hundred and seven patients received radical resection of thoracic esophageal
      carcinoma from May 2002 to June 2006 in our hospital, and their pre-operative CT
      images were transmitted to the three-dimensional conformal radiotherapy planning
      system by the network in digital format. Esophageal GTV targets were outlined and
      their GTV volumes were calculated. To analyze whether there is a relationship
      between GTV volume and pathologic lymph node metastasis or prognosis. RESULTS: In
      the 607 cases of esophageal carcinoma, the GTV volume was (22.5 +/- 16.8) cm(3)
      in 374 stage N0 EC patients, significantly different from that of (30.4 +/- 20.1)
      cm(3) in 233 stage N1 EC cases (P < 0.001). There is a significant difference
      between the GTV volumes of the groups with and without lymph node metastasis (P <
      0.05). There was a significant difference of the GTV volumes of EC patients with
      one lymph node metastasis and those with >= 4 lymph node metastasis (P < 0.05).
      There was a positive correlation between GTV volume and the number of lymph node
      metastasis (r = 0.230, P < 0.001). The 1-, 3-, 5-year survival rates since the
      surgery date were 83.8%, 53.5%, and 36.4%, respectively. There was a significant
      difference between the survival rates of stage N0 (48.5%) and stage N1 patients
      (18.2%, P < 0.001), and there was a significant difference between the survival
      rats of patients with 0, 1 and >= 2 lymph node metastasis (P < 0.01). Cox
      regression model analysis showed that GTV volume, number of lymph node
      metastasis, pathological type, and lesion site were independent prognostic
      factors (all P < 0.05). CONCLUSION: The GTV volume of esophageal carcinoma is
      positively correlated with the number of pathologic lymph node metastasis, and it
      is an independent prognostic factor for this cancer.

PMID- 23159083
TI  - [Clinical features and drug resistance characteristics of ovarian clear cell
      adenocarcinoma and analysis of its prognostic factors].
AB  - OBJECTIVE: To investigate the clinical features and factors involved in the drug
      resistance and prognosis of ovarian clear cell adenocarcinoma (OCCA). METHODS:
      Forty-seven OCCA patients and 53 ovarian serous cyst adenocarcinoma (OSCA)
      patients were included in this study. Their clinical characteristics, drug
      resistance, and prognostic factors were analyzed. RESULTS: The onset age of OCCA
      was (49.09 + 11.80) years old, and that of OSCA was (55.51 + 1.38) year old.
      There were 53.3% (24/45) of OCCA and 98.0% (50/51) of OSCA patients who had
      elevated CA125 levels. There were 46.8% (22/47) of OCCA patients and 7.5% (4/53)
      of OSCA patients who suffered from endometriosis (EMS). The percentage of early
      stage (stage I and stage II) OCCA was 80.9% (38/47), and that of OSCA was 11.3%
      (6/53). A statistically significant difference was observed on all these aspects
      (P < 0.05). The percentage of drug resistant OCCA was 26.1% (12/46), and that of
      OSCA was 24.0% (12/50), with a non-significant difference (P = 0.814).Among the
      patients with advanced stage disease, the percentage of drug resistance was 87.5%
      (7/8) for OCCA, while that of OSCA was 25.0% (11/44), showing a statistically
      significant difference (P = 0.003). Multiple logistic regression analysis
      revealed that OCCA (OR = 21.774, 95%CI: 2.438 to 194.431) and advanced stage (OR
      = 58.329, 95%CI: 5.750 to 591.703) were independent risk factors of drug
      resistance in ovarian epithelial cancers. For the advanced stage patients, the
      median overall survival time of OCCA and OSCA were 11 and 29 months,
      respectively, with a statistically significant difference (P = 0.000). Cox
      survival analysis showed that OCCA, advanced stage, suboptimal surgery, fewer
      than 6 cycles of chemotherapy and drug resistance were all risk factors of OS in
      ovarian cancer patients (P < 0.05). CONCLUSIONS: The age of onset in OCCA
      patients is younger than that of OSCA patients. The proportion of combination
      with endometriosis (EMS) is higher, and more early stage disease is observed in
      OCCA patients. The percentage of drug resistant in OCCA is higher, especially in
      advanced stage patients. The prognosis of advanced stage OCCA patients is poorer
      than that of OSCA patients in advanced stage.

PMID- 23159084
TI  - [Clinical analysis of childhood and adolescent Hodgkin's lymphoma: a report of 88
      cases].
AB  - OBJECTIVE: The aim of this study was to investigate the clinicopathological
      characteristics, effective treatment and prognosis in childhood and adolescent
      Hodgkin's lymphoma. METHODS: A total of 88 patients with childhood and adolescent
      Hodgkin's lymphoma were treated in the Cancer Hospital of CAMS from 1998 to 2005.
      The clinicopathological and follow-up data of the patients were retrospectively
      reviewed. The survival rate was calculated by Kaplan-Meier method and compared by
      log-rank test. COX multivariate prognosis analysis was performed. RESULTS: The 2
      year event-free survival rate of the 88 patients was 86.4%, the 5-year event-free
      survival rate was 61.4%, and the 5-year overall survival rate was 95.5%.
      Univariate analysis showed that the stage of disease (P = 0.033), "B" symptoms (P
      = 0.028), bulky disease (P = 0.007), splenomegaly (P = 0.050), LDH elevation (P =
      0.020), chemotherapy regimen (P = 0.003) were prognostic factors in the 5-year
      event-free survival rate. Splenomegaly (P = 0.039), LDH elevation (P = 0.033),
      chemotherapy regimen (P = 0.008) were prognostic factors of 5-year overall
      survival rate. Multivariate analysis showed that chemotherapy regimen (P =
      0.033), stage of disease (P = 0.023), LDH elevation (P = 0.008), "B" symptoms (P
      = 0.044), bulky disease (P = 0.009) were independent prognostic factors of 5-year
      event-free survival rate. The chemotherapy regimen (P = 0.012) and LDH elevation
      (P = 0.046) were independent prognostic factors of 5-year overall survival rate.
      CONCLUSIONS: The non-ABVD chemotherapy regimen, stage IV disease, LDH elevation,
      associated with "B" symptoms and bulky disease are independent prognostic factors
      of 5-year event-free survival rate. LDH elevation and non-ABVD chemotherapy
      regimen are independent prognostic factors of 5-year overall survival rate.

PMID- 23159085
TI  - [Surgical treatment and prognostic analysis of 109 patients with primary
      esophageal small cell carcinoma].
AB  - OBJECTIVE: Since the principles of treatment of primary esophageal small cell
      carcinoma (PESCC) remain still in controversy, the aim of this study was to
      investigate the clinical characteristics, treatment modalities and prognostic
      factors of this malignancy. METHODS: The clinical data of 109 patients treated by
      surgery in our hospital between October 1989 and April 2009 were retrospectively
      reviewed and analyzed. According to the most recently published TNM staging
      system for esophageal cancer (AJCC 2009), there were 17 patients in stage Ib, 31
      patients in stage II, 59 patients in stage III, and 2 patients in stage IV. All
      the data were analyzed using SPSS 15.0 software. The median survival time (MST)
      and overall survival rate (OS) were calculated and compared by the Kaplan-Meier
      method and log-rank test. The prognostic factors were calculated by Cox hazard
      regression model. RESULTS: Among all the 109 patients included, 93 patients were
      treated by radical esophagectomy, and 11 patients by palliative resection, while
      5 patients by exploration. The median survival time (MST) of the whole group was
      14.4 months and the 1-, 3- and 5-year overall survival rates (OS) were 56.9%,
      17.6%, and 12.0%, respectively. The median survival time (MST) and 5-year overall
      survival rates (OS) were 18.5 months and 21.4% for pathological N0 cases, 23.5
      months and 24.0% for N1 cases, 8.5 months and 0% for N2 cases, and 10.5 months
      and 0% for N3 cases, respectively (P < 0.001). The MST and 1-, 3- and 5-year OS
      of patients treated with postoperative chemotherapy were 17.0 months, 60.7%,
      19.8%, and 13.0%, respectively, statistically significantly longer than the 7.0
      months, 28.5%, 8.9% and 8.9%, respectively, of the patients without chemotherapy
      (P = 0.005). The pathological N stage and postoperative chemotherapy were
      independent prognostic factors by Cox multivariate analysis. CONCLUSIONS: Primary
      esophageal small cell carcinoma is an aggressive systemic disease, characterized
      by early and wide dissemination of lymph nodes and poor prognosis while treated
      with surgery or chemotherapy alone. Multimodality treatment based on radical
      esophagectomy should be recommended for patients in pathological stage I and II.

PMID- 23159086
TI  - [Analysis of prognostic factors of non-small cell lung cancer in patients under
      40 years of age].
AB  - OBJECTIVE: To investigate the prognostic factors for non-small cell lung
      cancer(NSCLC)in patients under 40 years of age. METHODS: The clinicopathological
      data of 148 young patients with NSCLC were retrospectively analyzed. Kaplan-Meier
      and Cox regression analyses were used to analyze the relationship between
      prognostic factors and survival time. RESULTS: The patients were followed-up for
      6 - 148 months, and the follow-up rate was 100%. In the whole group, 122 patients
      died and 26 cases were surviving. The 1-, 3- and 5-year survival rates were
      54.7%, 10.4% and 5.6%, respectively. The median survival time (MST) was 14.7
      months. Kaplan-Meier analysis showed that Karnofsky performance status (KPS),
      clinical stage, treatment modality and serum CEA were related with prognosis (P <
      0.05). Multivariate analysis indicated that KPS, clinical stage, treatment
      modality and serum CEA were independent prognostic factors (P < 0.05).
      CONCLUSIONS: KPS, CEA, clinical stage and treatment modalities are independent
      prognostic factors in young NSCLC patients.

PMID- 23159087
TI  - [Evaluation of the efficacy and prognostic factors for colorectal liver
      metastases treated with transcatheter arterial chemoembolization].
AB  - OBJECTIVE: The aim of this study was to evaluate the therapeutic efficacy and to
      determine the prognostic factors of TACE in patients with colorectal liver
      metastases (CRLM). METHODS: The clinical data of 183 patients with unresectable
      CRLM treated with TACE from Jan. 2002 to Dec. 2008 were retrospectively reviewed.
      Log-rank method was used for univariate analysis and Cox proportional hazard
      model was used for multivariate analysis of the prognostic factors. RESULTS: The
      median survival time was 22 months, and the 0.5-, 1-, 2-, 3-, 5-year survival
      rates were 93.9%, 81.1%, 39.8%, 18.2%, and 3.9%, respectively. Multivariate
      analysis showed that tumor involved more than one lobe of the liver, and elevated
      CEA and CA19-9 levels were independent risk factors for the overall survival (P <
      0.01). Females, more times of TACE, combination with regional therapy and
      received phase II resection were related with a good survival (P < 0.01) in CRLM
      patients after TACE treatment. CONCLUSIONS: Transcatheter arterial
      chemoembolization is an effective therapy for unresectable colorectal liver
      metastases. Patients with tumor spread more than one lobe of the liver, high CEA
      and CA19-9 levels are independent poor prognostic factors. Females, patients
      received more times of TACE, combined with regional therapy and received phase II
      resection may have a good survival.

PMID- 23159088
TI  - [Efficacy of docetaxel and nedaplatin combined with concurrent intensity
      modulated radiation therapy in the treatment of esophageal cancer].

PMID- 23159089
TI  - [The incidence and mortality of lung cancer among residents in Yangpu district of
      Shanghai from 2002 to 2010].
AB  - OBJECTIVE: To analyze the incidence and mortality of lung cancer patients among
      residents in Yangpu District of Shanghai from 2002 to 2010. METHODS: The data of
      lung cancer cases in permanent residents of Yangpu district were collected from
      the database of the registration and management system in Shanghai city. Temporal
      trend in the incidence of lung cancer was analyzed by using annual percent change
      (APC) mode1. The survivals were calculated using SPSS 16.0 and Joinpoint
      Regression Program 3.5.1 software. RESULTS: A total of 5726 cases of lung cancer
      were diagnosed from January 2002 to December 2010. Of those, 3865 were males with
      an average age of onset 70.08 years, and 1861 were females with an average age of
      onset 70.88 years. The crude incidence rate was 77.36/10(5) in men, significantly
      higher than 39.31/10(5) in women (U = 24.84, P < 0.01). The standardized
      incidence rate was 25.23/10(5) in men, significantly higher than 13.47/10(5) in
      women (U = 13.24, P < 0.01). A total of 5248 cases died of the disease in this
      period. Of those, 3586 were men. The crude mortality was 71.77/10(5) in men,
      significantly higher than 35.11/10(5) in women (U = 24.67, P < 0.01). The
      standardized mortality was 21.72/10(5) in men, significantly higher than
      11.08/10(5) in women (U = 13.01, P < 0.01). Both the incidence and mortality
      rates increased apparently in those older than 45 years. The 1- to 5-year
      survival rates in all cases were 37.42%, 22.71%, 15.73%, 12.32%, and 10.53%,
      respectively. The 1- to 5-year survival rates in male cases were significantly
      lower than those in female cases (P < 0.05 for each comparison). The 1- to 5-year
      survival rates of the patients whose tumor had been surgically removed were
      significantly higher than those in the patients without surgery (P < 0.05 for
      each comparison). CONCLUSIONS: The incidence of lung cancer is close to the
      mortality in the residents of Yangpu District of Shanghai city. Surgical
      resection treatment improves the prognosis of lung cancer.

PMID- 23159090
TI  - [Can hormone replacement therapy be used following treatment for gynecologic
      malignancies?].

PMID- 23159091
TI  - Evolution of infectious bronchitis virus in Taiwan: positively selected sites in
      the nucleocapsid protein and their effects on RNA-binding activity.
AB  - RNA recombination has been shown to underlie the sporadic emergence of new
      variants of coronavirus, including the infectious bronchitis virus (IBV), a
      highly contagious avian pathogen. We have demonstrated that RNA recombination can
      give rise to a new viral population, supported by the finding that most isolated
      Taiwanese (TW) IBVs, similar to Chinese (CH) IBVs, exhibit a genetic
      rearrangement with the American (US) IBV at the 5' end of the nucleocapsid (N)
      gene. Here, we further show that positive selection has occurred at two sites
      within the putative crossover region of the N-terminal domain (NTD) of the TW IBV
      N protein. Based on the crystal structure of the NTD, the stereographic positions
      of both predicted selected sites do not fall close to the RNA-binding groove.
      Surprisingly, converting either of the two residues to the amino acid present in
      most CH IBVs resulted in significantly reduced affinity of the N protein for the
      synthetic RNA repeats of the viral transcriptional regulatory sequence. These
      results suggest that modulating the amino acid residue at either selected site
      may alter the conformation of the N protein and affect the viral RNA-N
      interaction. This study illustrates that the N protein of the current TW IBV
      variant has been shaped by both RNA recombination and positive selection and that
      the latter may promote viral survival and fitness, potentially by increasing the
      RNA-binding capacity of the N protein.

PMID- 23159092
TI  - Effect of anterior-posterior and internal-external motion restraint during knee
      wear simulation on a posterior stabilised knee design.
AB  - The objective of our study was to examine the effect of biphaseal AP translation
      and IE rotation restraint, using a system defined specifically for posterior
      stabilised knee designs, on wear, kinematics and particle release in comparison
      to linear motion restraint as required by the established ISO 14243-1:2002(E)
      protocol. In the ISOlinear groups, an AP motion restraint of 30 N/mm and an IE
      rotation restraint of 0.6 Nm/ degrees  were applied in the knee wear simulation.
      In the ISOgap biphaseal groups with PCL sacrificing implants, the restraining AP
      force was zero in a +/-2.5mm range with, externally, a constant of 9.3N/mm
      applied proportionally to the AP translation of the tibia plateau, whereas the
      restraining IE torque was zero in a +/-6 degrees  range with, externally, a
      constant of 0.13 Nm/ degrees  applied proportionally to the IE rotation of the
      tibia plateau. Using the ISOgap biphaseal protocol on a posterior stabilised knee
      design, we found an increase of 41% in AP translation and of 131% in IE rotation,
      resulting in a 3.2-fold higher wear rate compared to the results obtained using
      the ISOlinear protocol. Changes in AP translation and IE rotation ligament motion
      restraints have a high impact on knee joint kinematics and wear behaviour of a
      fixed bearing posterior stabilised knee design.

PMID- 23159093
TI  - Multi-unit sustained vibration loading platform for biological tissues: design,
      validation and experimentation.
AB  - The relationships between mechanical inputs and resulting biological tissue
      structure, composition, and metabolism are critical to detailing the nuances of
      tissue mechanobiology in both healthy and injured tissues. Developing a model
      system to test the mechanobiology of tissues ex-vivo is a complex task, as
      controlling chemical and mechanical boundary layers in-vitro are difficult to
      replicate. A novel multi-unit vibration loading platform for intervertebral discs
      was designed and validated with both independent electronic data and experimental
      loading of 6 bovine intervertebral discs (IVDs) and an equal number of unloaded
      controls. Sustained vibration was applied using closed-loop positional control of
      pushrods within four independent bioreactors with circulating phosphate buffered
      saline. The bioreactors were designed to be modular with removable components
      allowing for easy cleaning and replacement. The loading regime was chosen to
      maximize target mRNA expression as reported in previous research. Aggrecan,
      decorin, and versican mRNA all reported statistically significant increases above
      control levels. Biglycan, collagen type I and II showed no significant difference
      from the control group. Further study is required to determine the resulting
      effect of increased mRNA expressions on long-term disc health. However these
      results indicate that this research is past the proof of concept stage,
      supporting future studies of mechanobiology utilizing this new device. The next
      stage in developing this novel loading platform should consider modifying the
      tissue grips to explore the effects of different directional loading on different
      gene expression, and also loading different types of tissues.

PMID- 23159094
TI  - Inflow boundary conditions for image-based computational hemodynamics: impact of
      idealized versus measured velocity profiles in the human aorta.
AB  - Here we analyse the influence of assumptions made on boundary conditions (BCs)
      extracted from phase-contrast magnetic resonance imaging (PC-MRI) in vivo
      measured flow data, applied on hemodynamic models of human aorta. This study aims
      at investigating if the imposition of BCs based on defective information, even
      when measured and specific-to-the-subject, might lead to misleading numerical
      representations of the aortic hemodynamics. In detail, we focus on the influence
      of assumptions regarding velocity profiles at the inlet section of the ascending
      aorta, incorporating phase flow data within the computational model. The obtained
      results are compared in terms of disturbed shear and helical bulk flow
      structures, when the same measured flow rate is prescribed as inlet BC in terms
      of 3D or 1D (axial) measured or idealized velocity profiles. Our findings clearly
      indicate that: (1) the imposition of PC-MRI measured axial velocity profiles as
      inflow BC may capture disturbed shear with sufficient accuracy, without the need
      to prescribe (and measure) realistic fully 3D velocity profiles; (2) attention
      should be put in setting idealized or PC-MRI measured axial velocity profiles at
      the inlet boundaries of aortic computational models when bulk flow features are
      investigated, because helical flow structures are markedly affected by the BC
      prescribed at the inflow. We conclude that the plausibility of the assumption of
      idealized velocity profiles as inlet BCs in personalized computational models can
      lead to misleading representations of the aortic hemodynamics both in terms of
      disturbed shear and bulk flow structures.

PMID- 23159095
TI  - A computational exploration of helical arterio-venous graft designs.
AB  - Although arterio-venous grafts (AVGs) are the second best option as long-term
      vascular access for hemodialysis, they suffer from complications caused by
      intimal hyperplasia, mainly located in vessel regions of low and oscillating wall
      shear stress. However, certain flow patterns in the bulk may reduce these
      unfavorable hemodynamic conditions. We therefore studied, with computational
      fluid dynamics (CFD), the impact of a helical AVG design on the occurrence of
      (un)favorable hemodynamic conditions at the venous anastomosis. Six CFD-models of
      an AVG in closed-loop configuration were constructed: one conventional straight
      graft, and five helical designed grafts with a pitch of 105 mm down to 35 mm. At
      the venous anastomosis, disturbed shear was assessed by quantifying the area with
      unfavorable conditions, and by analyzing averaged values in a case-specific
      patch. The bulk hemodynamics were assessed by analyzing the kinetic helicity in
      and the pressure drop over the graft. The most helical design scores best, being
      instrumental to suppress disturbed shear in the venous segment. There is,
      however, no trivial relationship between the number of helix turns of the graft
      and disturbed shear in the venous segment, when a realistic closed-loop AVG model
      is investigated. Bulk flow investigation showed a marked increase of helicity
      intensity in, and a moderate pressure drop over the AVG by introducing a lower
      pitch. At the venous anastomosis, unfavorable hemodynamic conditions can be
      reduced by introducing a helical design. However, due to the complex flow
      conditions, the optimal helical design for an AVG cannot be derived without
      studying case by case.

PMID- 23159097
TI  - Numerical and experimental evaluation of platelet deposition to collagen coated
      surface at low shear rates.
AB  - Platelet deposition to collagen-coated surface under low shear conditions was
      investigated using an experimental model. The flow chamber was created by
      combining a stationary and a rotational glass plates spaced 50 MUm apart. Blood
      filled into this space was subjected to a simple Couette flow. Both glass plates
      were covered with albumin to render them anti-thrombogenic. However, one spot 1*1
      mm in size was covered with collagen. This spot was where the platelets
      deposited. The device was mounted on an inverted microscope and the platelet
      deposition was recorded. Platelets were dyed to render them fluorescent. The
      blood used was human blood from healthy volunteers. It was subjected to a range
      of low shear rates (below 7001/s) to find out how they act on platelet
      deposition. The results show a characteristic curve with elevated platelet
      deposition in the range of 1501/s. For the interpretation of these results a
      numerical model was developed. It applies the Monte Carlo method to model a
      random walk of platelets. This diffusive motion was superimposed on the
      convective motion by the Couette flow. A satisfactory match to the experimental
      data was achieved.

PMID- 23159096
TI  - Controlled treadmill exercise eliminates chondroid deposits and restores tensile
      properties in a new murine tendinopathy model.
AB  - Tendinopathy is a widespread and disabling condition characterized by collagen
      fiber disruption and accumulation of a glycosaminoglycan-rich chondroid matrix.
      Recent clinical reports have illustrated the potential of mechanical loading
      (exercise) therapies to successfully treat chronic tendinopathies. We have
      developed a new murine tendinopathy model which requires a single injection of
      TGF-beta1 into the Achilles tendon midsubstance followed by normal cage activity
      for 2 weeks. At this time, tendon maximum stress showed a dramatic (66%)
      reduction relative to that of normal controls and this persisted at four weeks.
      Loss of material properties was accompanied by abundant chondroid cells within
      the tendon (closely resembling the changes observed in human samples obtained
      intra-operatively) and increased expression of Acan, Col1a1, Col2a1, Col3a1, Fn1
      and Mmp3. Mice subjected to two weeks of daily treadmill exercise following TGF
      beta1 injection showed a similar reduction in tendon material properties as the
      caged group. However, in mice subjected to 4 weeks of treadmill exercise, tendon
      maximum stress values were similar to those of naive controls. Tendons from the
      mice exercised for 4 weeks showed essentially no chondroid cells and the
      expression of Acan, Col1a1, Col2a1, Col3a1, and Mmp3 was significantly reduced
      relative to the 4-week cage group. This technically simple murine tendinopathy
      model is highly amenable to detailed mechanistic and translational studies of the
      biomechanical and cell biological pathways, that could be targeted to enhance
      healing of tendinopathy.

PMID- 23159098
TI  - Assessing gait stability: the influence of state space reconstruction on inter-
      and intra-day reliability of local dynamic stability during over-ground walking.
AB  - Estimating local dynamic stability is considered a powerful approach to identify
      persons with balance impairments. Its validity has been studied extensively, and
      provides evidence that short-term local dynamic stability is related to balance
      impairments and the risk of falling. Thus far, however, this relation has only
      been proven on group level. For clinical use, differences on the individual level
      should also be detectable, requiring reliability to be high. In the current
      study, reliability of short-term local dynamic stability was investigated within
      and between days. Participants walked 500 m back and forth on a straight outdoor
      footpath, on 2 non-consecutive days, and 3D linear accelerations were measured
      using an accelerometer (DynaPort MiniMod). The state space was reconstructed
      using 4 common approaches, all based on delay embedding. Within-session intra
      class correlation coefficients were good (>=0.70), however between-session intra
      class correlation coefficients were poor to moderate (<=0.63) and influenced by
      the reconstruction method. The same holds for the smallest detectable difference,
      which ranged from 17% to 46% depending on the state space reconstruction method.
      The best within- and between-session intra-class correlation coefficients and
      smallest detectable differences were achieved with a state space reconstruction
      with a fixed time delay and number of embedding dimensions. Overall, due to the
      influence of biological variation and measurement error, the short-term local
      dynamic stability can only be used to detect substantial differences on the
      individual level.

PMID- 23159099
TI  - Epicardial adipose tissue volume and cardiovascular disease in hemodialysis
      patients.
AB  - OBJECTIVE: Epicardial adipose tissue (EAT) is proposed as a cardiovascular risk
      marker in non-uremic subjects. However, little is known about its role in
      patients with higher cardiovascular risk profile such as chronic kidney disease.
      The aim of this study was to investigate the relationship between EAT and several
      cardiovascular surrogate markers (coronary artery calcification (CAC), arterial
      stiffness and atherosclerosis) in patients on maintenance hemodialysis. METHODS:
      A total of 191 prevalent hemodialysis patients were enrolled in this cross
      sectional study. EAT and CAC scores (CACs) were determined by multi-slice
      computerized tomography, arterial stiffness by carotid-femoral pulse wave
      velocity (PWV), and carotid artery intima-media thickness (CA-IMT) by B-mode
      doppler ultrasonography. RESULTS: Mean age was 59 +/- 13 years and time on
      hemodialysis 75 +/- 44 months. Twenty percent of the patients had diabetes. Mean
      EAT volume was 62.6 +/- 26.8 cm(3)/m(2). Mean CA-IMT and PWV values increased
      across the EAT tertiles. EAT was correlated with age, female gender, body mass
      index, albumin and lipid parameters. Additionally, CA-IMT and PWV values were
      positively correlated with EAT. EAT volume was significantly higher in patients
      with CACs >10 compared to the patients with CACs <=10. Despite the univariate
      associations between EAT and cardiovascular surrogate markers, only age, body
      mass index and total cholesterol levels were associated with EAT in adjusted
      models. CONCLUSIONS: In prevalent hemodialysis patients, EAT is correlated with
      atherosclerosis, arterial stiffness and the presence of CAC. However, this
      correlation is not independent of other risk factors.

PMID- 23159100
TI  - Association between circulating matrix metalloproteinase levels and coronary
      plaque regression after acute coronary syndrome--subanalysis of the JAPAN-ACS
      study.
AB  - BACKGROUND: Matrix metalloproteinases (MMPs) have been implicated in development
      of atherosclerosis. MMPs are activated in patients with acute coronary syndrome
      (ACS). However, little data exist regarding the correlation between circulating
      levels of MMPs and plaque volume (PV) in patients with ACS. We therefore
      evaluated the impact of MMPs on coronary PV as a post hoc analysis from the JAPAN
      ACS study. METHODS: The multicenter JAPAN-ACS trial revealed that aggressive
      statin therapy for patients with ACS significantly reduces coronary PV determined
      by intravascular ultrasound (IVUS). We studied 248 ACS patients who had serial
      IVUS examinations over 8-12 months in the trial. For each patient, MMP-1, 2, and
      3 were measured both at baseline and at study end to evaluate the correlation
      between the percent change of PV and MMP levels. RESULTS: MMP-3 levels were
      significantly decreased during the follow-up period (100 ng/mL to 73 ng/mL, p <
      0.001), in contrast, MMP-1, -2 levels were significantly increased. MMP-3 levels
      at follow-up correlated with coronary plaque regression (p for trend = 0.016). A
      multivariable linear regression model showed both MMP-2 and MMP-3 levels at
      follow-up were independent variables for change of coronary PV (p = 0.038 and p =
      0.016, respectively). CONCLUSION: Circulating MMPs levels are associated with
      changes in coronary plaque volume determined by serial IVUS in patients with ACS.

PMID- 23159101
TI  - Carotid intima-media thickness in patients with subclinical hypothyroidism: a
      meta-analysis.
AB  - OBJECTIVE: Subclinical hypothyroidism (SCH) has been associated with increased
      carotid intima-media thickness (IMT) in recent studies, but this relationship is
      controversial. The aim of this study was to assess whether carotid IMT in
      patients with SCH differs from that in euthyroid subjects. METHODS: Prior to
      November 2011, we searched PUBMED, EMBASE, COCHRANE LIBRARY databases and the
      bibliographies of key articles to identify studies that reported carotid IMT in
      patients with SCH compared with euthyroid subjects. Two reviewers independently
      evaluated each potential study for eligibility, assessed the methodological
      quality, and extracted the data. RESULTS: We identified 8 observational studies
      with 3602 patients that met the eligibility criteria. In patients with SCH, the
      pooled estimate of the weighted mean difference (WMD) of increased carotid IMT
      was 0.056 mm (95% CI 0.020, 0.092; P = 0.002). Sensitivity analysis using a
      pooled sample of the 7 higher-quality studies demonstrated higher carotid IMT
      level in patients with SCH compared with those with euthyroidism (WMD, 0.064 mm,
      95% CI 0.024, 0.105; P = 0.002). In a subgroup analysis, SCH was also associated
      with a significant increase in carotid IMT among patients with a mean TSH > 10.0
      mIU/l (WMD, 0.082 mm, 95% CI 0.049, 0.116; P = 0.00). SCH was associated with a
      significant increase in systolic blood pressure (SBP), triglyceride (TG) levels,
      total cholesterol (TC) levels, low-density lipoprotein (LDL) levels and with a
      decrease in fasting plasma glucose (FPG). CONCLUSION: This meta-analysis
      indicates that SCH is associated with an increased carotid IMT, which may due to
      elevated thyrotropin (TSH), dyslipidemia and hypertension. Increased IMT can also
      be present in patients with serum TSH values less than 10 mIU/l, although there
      is significant heterogeneity. Prospective studies with larger samples are
      necessary to evaluate these observations.

PMID- 23159102
TI  - [Radiopaque mass detected on orthopantomogram].

PMID- 23159103
TI  - Could heterotopic ossification be prevented by varying dietary n-3/n-6
      polyunsaturated fatty acid ratio: a novel perspective to its treatment?
AB  - Heterotopic ossification (HO) is a common complication following with
      musculoskeletal trauma and surgical procedures. It usually decreases joint
      mobility and eventually causes loss of joint function. Despite nonsteroidal anti
      inflammatory drugs (NSAIDs), the inhibitor of cyclooxygenase(COX), have been
      proven to prevent HO effectively via prostaglandin E2 synthesis regulation and
      modulation of tissue responsiveness to pro-inflammatory signaling, HO prevention
      is still a matter of debate for clinicians to avoid the side effect of NSAIDs.
      Interestingly, it is suggested that PGE2 production and pro-inflammatory
      microenvironment in body could be modified by varying the ratio of the precursor
      fatty acids in the diet. On account of the effect of dietary (n-6)/(n-3) PUFAs
      ratio on both COX metabolism and pro-inflammatory cytokines mediated biological
      responsiveness, we hypothesized lowering dietary (n-6)/(n-3) PUFAs ratio may not
      only directly reduce the substrate of COX-2 and COX-2 activity, but also
      partially ameliorate tissue inflammatory responsiveness to cytokines correlated
      with HO development,exerting an inhibitory effect on PGE2 synthesis to prevent HO
      formation. The negative role of lowering dietary (n-6)/(n-3) PUFAs ratio on
      angiogenesis, cytokines-induced apoptosis, inflammatory responsiveness and
      osteogenesis could also contribute to its action on HO development. If our
      hypothesis is proved to be corrected, it could be an innovative method to treat
      HO.

PMID- 23159104
TI  - Role of clinical diagnosis of ventilator-associated pneumonia.

PMID- 23159105
TI  - Certification of diabetes-related mortality: the need for an international
      guideline.

PMID- 23159106
TI  - Ethanol modulates the neurovascular coupling.
AB  - Despite some evidence of the underlying molecular mechanisms the neuronal basis
      of ethanol-induced effects on the neurovascular coupling that forms the BOLD
      (blood oxygenation level dependent) signal is poorly understood. In a recent fMRI
      (functional magnetic resonance imaging) study monitoring ethanol-induced changes
      of the BOLD signal a reduction of the amplitude and a prolongation of the BOLD
      signal were observed. However, the BOLD signal is assumed to consist of a complex
      superposition of different underlying signals. To gain insight how ethanol
      influences stimulus efficacy, oxygen extraction, transit time and vessel-related
      parameters the fMRI time series from the sensori-motor and the visual cortex were
      analyzed using the balloon model. The results show a region-dependent decrease of
      the stimulus efficacy to trigger a post-stimulus neurovascular response as well
      as a prolongation of the transit time through the venous compartment. Oxygen
      extraction, feedback mechanisms and other vessel-related parameters were not
      affected. The results may be interpreted as follows: the overall mechanisms of
      the neurovascular coupling are still acting well at the moderate ethanol level of
      about 0.80/00 (in particular the vessel-related parts), but the potency to evoke
      a neurovascular response is already compromised most obviously in the
      supplementary motor area responsible for complex synchronizing and planning
      processes.

PMID- 23159107
TI  - [Analysis of the diastolic function by myocardial perfusion gated SPECT after
      coronary revascularization in acute myocardial infarction].
AB  - OBJECTIVE: To evaluate the evolutive changes in diastolic function after
      percutaneous coronary revascularization (PCR) in acute myocardial infarction
      (AMI), using myocardial perfusion gated SPECT. METHODS: Thirty-two patients (mean
      61.9+/-9.7 years, 7 women) were studied by two at rest gated SPECT: the first
      gated-SPECT-1 was performed with an injection of a dose of (99m)Tc-tetrofosmin
      prior to PCR and the second gated-SPECT-2 between the fourth and fifth weeks
      after AMI. Changes of peak filling rate (PFR) and the time to peak filling rate
      (TTPF) were assessed between both studies, and were related to the extent of
      salvaged myocardium (SM), end-diastolic (EDV) and end-systolic (ESV) volumes, and
      left ventricular ejection fraction (LVEF) changes. RESULTS: An improvement was
      observed in diastolic function parameters Gated-SPECT-2: PFR increased
      significantly (P=0.011) while the TTPF decreased without reaching statistical
      significance (P=0.288). In multivariate analysis, adjusted by clinical and
      coronary variables, improvement of PFR was significantly associated with
      percentage of SM (P=0.030), increase in LVEF (P=0.004) and with ESV volume
      reduction (P=0.005). Improvement of TTPF was only related significantly to the
      percentage of SM (P=0.046). PFR increased 0.01 EDV/sec. and TTPF decreased 1.14ms
      for each cm(2) increase of the area of SM. CONCLUSIONS: After PCR in AMI, the
      myocardial perfusion gated SPECT makes it possible to assess the significant
      improvement in diastolic function mainly related to the amount of MS.

PMID- 23159108
TI  - Detection of BRAF p.V600E mutations in melanomas: comparison of four methods
      argues for sequential use of immunohistochemistry and pyrosequencing.
AB  - BRAF p.V600 mutation detection recently became necessary to treat metastatic
      melanoma patients with vemurafenib. This study compares different methods of
      detection of BRAF mutations. Melanoma samples from 111 patients were analyzed for
      BRAF mutations, and for 89 of them, results were obtained with the four following
      methods: Sanger sequencing, real-time PCR, immunohistochemistry, and
      pyrosequencing. All samples contained at least 60% of tumor cells. Directional
      Sanger sequencing of PCR products failed to detect 3 of 40 p.V600E-mutated cases
      (7.5%) (sensitivity, 92.5%; 95% CI, 78.5% to 98.0%). BRAF p.V600E-specific real
      time PCR identified 39 of 40 p.V600E-mutated cases (97.6%) (sensitivity, 97.5%;
      95% CI, 87.1% to 99.6%) and all 39 wild-type (WT) cases and surprisingly was also
      positive for 6/6 p.V600K (specificity, 87.8%; 95% CI, 75.8% to 94.3%). However,
      other mutations, p.V600R (n = 1), p.K601E (n = 2), and p.600_601delinsE (n = 1),
      were not detected. Immunohistochemistry with VE1, specific for p.V600E,
      identified all p.V600E and WT cases (sensitivity, 100%; 95% CI, 91.2% to 100%)
      but was negative for all other BRAF mutations. Pyrosequencing successfully
      identified all WT and mutated cases. Immunohistochemistry is highly specific for
      p.V600E, and could be used as a first-line method, as is currently performed for
      HER2 amplification detection. Pyrosequencing proved to be the most efficient
      method to detect BRAF mutations in melanomas and could be performed on VE1
      negative or uninterpretable cases.

PMID- 23159109
TI  - Underestimation of the resistance of Mycobacterium tuberculosis to second-line
      drugs by the new GenoType MTBDRsl test.
AB  - The GenoType MTBDRsl is a new-generation PCR-based line-probe assay for the
      detection of extensively drug-resistant tuberculosis (XDR-TB). This study
      evaluated the performance of MTBDRsl in detecting genotypic resistance to
      ethambutol, kanamycin, and ofloxacin in Mycobacterium tuberculosis (MTB) strains.
      The drug resistance of 262 unique clinical MTB isolates from China was analyzed
      with MTBDRsl, traditional TB drug susceptibility testing (DST), and sequencing.
      Sensitivity of MTBDRsl was 62.4% (93/149; 95% CI = 54.1 to 70.2) for detection of
      ethambutol resistance, 57.9% (55/95; 95% CI = 47.3 to 68) for kanamycin
      resistance, and 81% (111/137; 95% CI = 73.4 to 87.2) for ofloxacin resistance;
      specificity was 76.8% (86/112; 95% CI = 67.9 to 84.2), 98.8% (164/166; 95% CI =
      95.7 to 99.9), and 91.1% (113/124; 95% CI = 84.7 to 95.5), respectively.
      Sequencing suggested that 36.9% (55/149) of ethambutol-resistant strains had no
      embB306 mutation and that 26.8% (40/149) had embB497 mutation not covered by
      MTBDRsl. Furthermore, MTBDRsl indicated ethambutol resistance in 23.2% (26/112)
      of ethambutol-susceptible strains, of which 92.3% (24/26) were confirmed
      resistant by sequencing. This study demonstrated that genotypic resistance to
      ethambutol, kanamycin, and ofloxacin in MTB can be quickly determined with the
      MTBDRsl. As a rapid and convenient genetic method, this assay could function as a
      supplement to traditional DST. More relevant genetic markers are needed to
      improve sensitivity.

PMID- 23159110
TI  - Medical school-based education in dentistry: an exciting history and an opportune
      future.

PMID- 23159111
TI  - The relationship of denosumab pharmacology and osteonecrosis of the jaws.
AB  - Denosumab is a new bone antiresorptive agent that has received approval by the
      Food and Drug Administration for use in patients with osteoporosis and metastatic
      cancer to the bones. Like the bisphosponates that are used as antiresorptive
      medications, denosumab has been associated with osteonecrosis of the jaws (ONJ).
      However, because the pharmacodynamics and pharmacokinetics of denosumab differ
      from that of the bisphosphonates, ONJ related to denosumab may resolve more
      rapidly with a drug holiday than bisphosphonate-related osteonecrosis of the jaws
      (BRONJ). This paper describes the management of a patient who developed ONJ while
      receiving denosumab, reviews the incidence of ONJ associated with denosumab, and
      compares the pharmacology of denosumab and the bisphosphonates. Because the
      effects of denosumab on bone turnover are more rapidly reversible than the
      effects of the bisphosphonates, ONJ related to denosumab may resolve more quickly
      with a drug holiday than BRONJ.

PMID- 23159112
TI  - Slowly growing swelling on body of the mandible with paresthesia on lower lip.
AB  - A 23-year-old female patient reported with the chief complaint of swelling on the
      lower left posterior teeth region of the jaw and paresthesia of left lower lip of
      6 months of duration. On the basis of clinical findings and conventional
      radiographic features, odontogenic tumor or cyst was suspected. Advanced imaging
      i.e. CT scan, Denta Scan, MRI further provided the exact nature, extent and
      location of the lesion and later on by histopathological examination, it was
      diagnosed as an intraosseous schwannoma of the mandible. In this
      clinicopathologic conference section, elaborate differential diagnosis and
      radiological features of this rare case is presented.

PMID- 23159113
TI  - A maxillary sinus tumor in an adolescent girl.

PMID- 23159115
TI  - Osteogenic genes related to the canonic WNT pathway are down-regulated in
      ameloblastoma.
AB  - OBJECTIVE: The aim of this study was to determine the expression of essential
      osteogenic genes related to the canonic WNT pathway, i.e., WDR5, sFRP-2, and
      their downstream genes, in ameloblastoma and to clarify their biologic impact on
      this neoplasm. STUDY DESIGN: Forty-six paraffin-embedded ameloblastoma samples
      and ameloblastic (AM-1) and preosteoblastic (KUSA/A1) cell lines were used.
      Immunohistochemistry, Western blot, reverse-transcription polymerase chain
      reaction, and alkaline phosphatase (ALP) activity assay were performed. RESULTS:
      WDR5, essential for osteoblast differentiation and canonic WNT pathway
      activation, was negative in most ameloblastoma cases and weakly expressed in AM-1
      cells. Conversely, sFRP-2s was overexpressed. RUNX2 and C-MYC, downstream
      inductions of canonic WNT pathway activation, demonstrated weak mRNA expressions
      in ameloblastoma, suggesting WNT pathway impairment and WDR5 functional
      inactivity. Recombinant WDR5 weakly induced ALP activity of KUSA/A1 cells
      cultured in AM-1 conditioned medium. CONCLUSIONS: These findings suggest that WNT
      related bone-forming genes are down-regulated in ameloblastoma. Concurrent sFRP-2
      overexpression suggests that both bone-forming and bone-inhibiting genes equally
      contributed to reduced bone formation in this neoplasm.

PMID- 23159114
TI  - Metagenomic investigation of microbes and viruses in patients with jaw
      osteonecrosis associated with bisphosphonate therapy.
AB  - OBJECTIVE: The goal of this preliminary study was to use metagenomic approaches
      to investigate the taxonomic diversity of microorganisms in patients with
      bisphosphonate-related osteonecrosis of the jaw (BRONJ). STUDY DESIGN: Samples of
      saliva for planktonic microbial analysis and biofilm cultivation were collected
      from 10 patients (5 with BRONJ and 5 non-BRONJ control subjects) who met all
      ascertainment criteria. Prophage induction experiments-16S rRNA polymerase chain
      reaction and 454 pyrosequencing-and epifluorescent microscopy were performed for
      characterization and enumeration of microbes and viruses. RESULTS: Three phyla of
      microbes-Proteobacteria (70%), Firmicutes (26.9%), and Actinobacteria (1.95%)
      dominated all BRONJ samples and accounted for almost 99% of the total data. Viral
      abundance was ~1 order of magnitude greater than microbial cell abundance and
      comprised mainly phage viruses. CONCLUSIONS: Individuals with jaw osteonecrosis
      harbored different microbial assemblages than nonaffected patients, and in
      general viral abundance and prophage induction increased with biofilm formation,
      suggesting that biofilm formation encouraged lysogenic interactions between
      viruses and microbial hosts and may contribute to pathogenicity.

PMID- 23159116
TI  - BRAF and GNAQ mutations in melanocytic tumors of the oral cavity.
AB  - OBJECTIVE: The genetic factors participating in oral melanoma evolution have not
      been studied extensively. We aimed to analyze the prevalence of BRAF and GNAQ
      mutations in a series of oral melanocytic tumors, nevi, and melanomas. STUDY
      DESIGN: The study group consisted of 4 melanomas and 10 nevi (6 intramucosal, 4
      blue nevi). DNA was extracted from paraffin-embedded tissue sections, and
      mutations in GNAQ and BRAF were analyzed with the use of mass spectrometery.
      RESULTS: V600E point mutation was identified in the BRAF gene in 3 intramucosal
      nevi and in 2 melanomas. Only 1 blue nevus harbored the GNAQ209 mutation. None of
      the BRAF-positive samples harbored GNAQ mutations. CONCLUSIONS: The finding of
      BRAF mutations in oral benign and malignant melanocytic lesions points to a
      potential initiating role of BRAF in malignant transformation, which may have
      important therapeutic implications as those with BRAF mutations may benefit from
      specific treatment using RAF inhibitors.

PMID- 23159117
TI  - Histopathological features of bisphosphonate-associated osteonecrosis: findings
      in patients treated with partial mandibulectomies.
AB  - The present study investigated the histopathologic and radiographic features of
      stage 3 bisphosphonate-associated osteonecrosis of the jaw (BAONJ) in patients
      who were treated with partial mandibulectomies. Bisphosphonates had been orally
      administered to 10 patients with osteoporosis and intravenously administered to 1
      patient with metastatic carcinoma. On radiographic images, massive osteolysis and
      periosteal bone formations were conspicuous, and a thin mandibular cortical width
      was observed in 5 of 10 osteoporosis patients despite the previous use of
      bisphosphonate. Microscopically, the mandibulectomy specimens of the patients
      could be divided into 4 distinct layers. Although there were few differences in
      overall histologic features between BAONJ and chronic suppurative osteomyelitis,
      a notable number of osteoclasts were found detached from the bony trabeculae in
      BAONJ.

PMID- 23159118
TI  - Incidental pneumoparotid detected on computed tomography: Should it raise an
      alarm?
AB  - BACKGROUND: Pneumoparotid is often seen in patients as a result of infection or
      following maneuvers that lead to increase in intraoral pressures. We describe a
      short series of 5 cases of incidental pneumoparotid, for the first time, detected
      during neck contrast-enhanced computed tomography (CECT) examination. METHODS:
      All neck CECT examinations that had been acquired over a 4-month period for
      indications other than pertaining to the parotid gland were retrospectively
      analyzed. RESULTS: Four hundred cases were reviewed. Five of 80 patients in whom
      CECT was acquired after the "puffed cheek" maneuver were detected to have
      incidental pneumoparotid. All remained clinically asymptomatic during the
      examination. CONCLUSIONS: Pneumoparotid may be an incidental finding in patients
      asked to blow air in a closed mouth during CT/magnetic resonance acquisition. An
      awareness of this benign finding would prevent sudden alarm of interpreting it as
      an anaerobic infection of the parotid in such patients.

PMID- 23159119
TI  - Calcifying cystic odontogenic tumor and adenomatoid odontogenic tumor:
      radiographic evaluation.
AB  - OBJECTIVES: The aim of this study was to describe the radiographic features of
      calcifying cystic odontogenic tumors (CCOTs) and adenomatoid odontogenic tumors
      (AOTs) and to compare the radiographic findings for these 2 lesions. STUDY
      DESIGN: We retrospectively reviewed radiographs of CCOTs and AOTs. Location,
      border, relationship of the lesion with the impacted tooth, calcification
      patterns, tooth displacement, and root resorption were evaluated. RESULTS: Nine
      CCOTs and 8 AOTs were reviewed. Most CCOTs and AOTs had smooth borders. Three
      CCOTs and 7 AOTs enclosed impacted teeth. Of these cases, the radiolucencies of 3
      CCOTs and 1 AOT were attached to the impacted teeth at the cementoenamel
      junctions. Three AOTs enclosed more portions of the roots, and the other 3 AOTs
      enclosed the entire teeth. Calcification in CCOTs appeared as a thin radiopaque
      line (2 cases) and discrete radiopaque foci (1 case), whereas AOTs had numerous
      dispersed or clustered radiopaque foci (4 cases). CONCLUSIONS: Radiolucency with
      numerous radiopaque foci (particularly when the radiolucency surrounds a portion
      of the root or entire tooth) is suggestive of an AOT rather than a CCOT.

PMID- 23159120
TI  - Prevalence of cone beam computed tomography imaging findings according to the
      clinical stage of bisphosphonate-related osteonecrosis of the jaw.
AB  - OBJECTIVES: Investigations of cone beam computed tomography (CBCT) for
      bisphosphonate-related osteonecrosis of the jaw (BRONJ) imaging are rare. The
      purpose of this study was to investigate the prevalence of typical radiological
      findings of BRONJ in CBCT. METHODS: Twenty-seven CBCTs of BRONJ sites were
      assessed on the basis of the radiological findings (cancellous bone destruction,
      cortical bone erosion, sequestration, osteosclerosis, and periostal bone
      formation) and put in relation to the severity of the BRONJ sites. RESULTS:
      Cancellous bone destruction and cortical bone erosion were the most common
      findings. Occurrence seems to decrease with decreasing BRONJ severity.
      Sequestration and osteosclerosis were less frequent and could be seen across all
      stages. Periosteal bone formation occurred in high-stage BRONJ only. CONCLUSION:
      Cancellous bone destruction, cortical bone erosion, sequestration, and
      osteosclerosis can be seen across all stages and prevalence seems to decrease
      with decreasing severity of BRONJ. The occurrence of periosteal new bone
      formation seems to start in high-stage BRONJ.

PMID- 23159121
TI  - Surgical removal of a third molar at risk for mandibular pathologic fracture:
      case report and clinical considerations.
AB  - Surgical removal of mandibular deeply impacted third molars may be challenging
      and could be associated with several possible risks. Intra- or postoperative
      mandibular fracture during or after third molar extraction is a major though rare
      complication. Before starting the surgical removal of a mandibular deeply
      impacted third molar, various predisposing factors of mandibular fracture should
      be considered and kept in mind: adult age, male sex, deep inclusion, tooth
      ankylosis, and associated bony pathology. The aim of this article is to report
      and discuss the surgical management of a mandibular deeply impacted third molar
      associated with a follicular cyst.

PMID- 23159122
TI  - Deep venous thrombosis: report of 2 cases.
AB  - Postsurgical deep venous thrombosis (DVT) is an established complication with
      rare incidence in maxillofacial surgery. We report 2 cases of postsurgical
      proximal DVT after hemimandibulectomy from 2000 to 2009 along with pathogenesis,
      clinical findings, and management of DVT.

PMID- 23159123
TI  - Gorham-Stout syndrome of the facial bones: a review of pathogenesis and treatment
      modalities and report of a case with a rare cutaneous manifestations.
AB  - Gorham disease is a very rare condition associated with spontaneous destruction
      and resorption of 1 or more bones anywhere in the body. Many authors have
      suggested and/or implicated trauma as the initiating factor in the majority of
      the reported cases. It can affect almost all bones, and a combination of bones
      has been reported. In the maxillofacial skeleton, the first facial case was
      reported by Romer in 1928. Until now, only a few cases of Gorham disease
      affecting the maxillofacial bones, including this case report, have been
      reported. We present a brief review of the pathogenesis and treatment modalities
      of the disease and report a very rare clinical picture of the disease affecting a
      young and otherwise healthy patient with massive osteolysis of the mandibular
      bone and extensive involvement of the mouth floor and skin of the chin, which to
      our knowledge, is the only case report with skin manifestation affecting the
      maxillofacial region. Such skin manifestations play an important role for the
      diagnosis and add a clue for management of such condition.

PMID- 23159124
TI  - Antibiotic prophylaxis in third molar surgery: a review.
AB  - OBJECTIVE: Controversy exists about the efficacy of antibiotic prophylaxis in
      preventing complications after lower third molar surgery. For evidence-based
      recommendation, a review was performed on clinical trials reporting the use of
      antibiotic prophylaxis compared with no treatment or placebo with "infection" as
      outcome. STUDY DESIGN: Useful studies were identified using Embase, Cochrane, and
      Ovid Medline (1966-January 2011) and references in retrieved reports and review
      articles. Twenty-three eligible studies were identified and reviewed by
      independent investigators using 2 quality assessment scales. RESULTS: The review
      procedure revealed 15 "low-quality" and 8 "high-quality" articles, with major
      differences in treatment modalities and heterogeneity of design. CONCLUSIONS:
      There is limited evidence supporting the efficacy of commonly used antibiotics in
      preventing complications after lower third molar removal. Well designed and well
      reported high-quality randomized trials considering known risk factors and taking
      clinical outcomes into account are needed to reach final consensus on the
      efficacy of antibiotic prophylaxis to allow evidence-based recommendations.

PMID- 23159125
TI  - Out but not in: the large transmembrane beta-barrel protein FhuA unfolds but
      cannot refold via beta-hairpins.
AB  - How transmembrane beta-barrel proteins insert and fold into membranes and by
      which factors they destabilize, unfold, and misfold represents a field of intense
      studies. Here, we use single-molecule force spectroscopy to characterize the un-
      and refolding of the ferric hydroxamate uptake receptor (FhuA), which is one of
      the largest beta-barrel proteins of the outer membrane of Escherichia coli.
      Applied to mechanical stress, FhuA undergoes a complex unfolding pathway in which
      each of the 11 beta-hairpins unfolds one after the other until the entire beta
      barrel has unfolded. Once unfolded and relaxed, the FhuA polypeptide cannot fold
      back into the lipid membrane and adopts various misfolded conformations. Such
      misfolding is in contrast to the reversible refolding behavior of much smaller
      beta-barrel outer membrane proteins OmpA and OmpG that occurs at similar
      experimental conditions. The results suggest that large beta-barrel proteins that
      show more complex (un-)folding pathways require cofactors for proper insertion
      and folding into the membrane.

PMID- 23159126
TI  - Design of a phosphorylatable PDZ domain with peptide-specific affinity changes.
AB  - Phosphorylation is one of the most common posttranslational modifications
      controlling cellular protein activity. Here, we describe a combined computational
      and experimental strategy to design new phosphorylation sites into globular
      proteins to regulate their functions. We target a peptide recognition protein,
      the Erbin PDZ domain, to be phosphorylated by cAMP-dependent protein kinase.
      Comparing the five successful designs to the unsuccessful cases, we find a trade
      off between protein stability and the ability to be modified by phosphorylation.
      In two designs, Erbin's peptide binding function is modified by phosphorylation,
      where the presence of the phosphate group destabilizes peptide binding. One of
      these showed an additional switch in specificity by introducing favorable
      interactions between a designed arginine in the peptide and phosphoserine on the
      PDZ domain. Because of the diversity of PDZ domains, this opens avenues for the
      design of related phosphoswitchable domains to create a repertoire of regulatable
      interaction parts for synthetic biology.

PMID- 23159127
TI  - A structure-based strategy for epitope discovery in Burkholderia pseudomallei
      OppA antigen.
AB  - We present an approach integrating structural and computational biology with
      immunological tests to identify epitopes in the OppA antigen from the Gram
      negative pathogen Burkholderia pseudomallei, the etiological agent of
      melioidosis. The crystal structure of OppA(Bp), reported here at 2.1 A
      resolution, was the basis for a computational analysis that identified three
      potential epitopes. In parallel, antigen proteolysis and immunocapturing allowed
      us to identify three additional peptides. All six potential epitopes were
      synthesized as free peptides and tested for their immunoreactivity against sera
      from healthy seronegative, healthy seropositive, and recovered melioidosis
      patients. Three synthetic peptides allowed the different patient groups to be
      distinguished, underlining the potential of this approach. Extension of the
      computational analysis, including energy-based decomposition methods, allowed
      rationalizing results of the predictive analyses and the immunocapture epitope
      mapping. Our results illustrate a structure-based epitope discovery process,
      whose application may expand our perspectives in the diagnostic and vaccine
      design fields.

PMID- 23159128
TI  - Evidence-based drug policy: it starts with good evidence and ends with policy
      reform.

PMID- 23159129
TI  - Low physical activity in patients with type 2 diabetes: the role of obesity.
AB  - AIMS: Few studies have described ambulatory activity in free-living individuals
      with type 2 diabetes mellitus (T2DM) using motion sensors, and none included a
      control group. For this reason, our study compared the physical-activity levels
      of outpatients with T2DM with subjects without diabetes, and examined the
      relationship between body mass index (BMI) and physical-activity parameters.
      METHODS: Physical-activity levels in 70 outpatients with T2DM and 30 age-, gender
      and employment-matched individuals without diabetes were measured using the
      SenseWear ArmbandTM, a monitoring device validated against doubly labelled water,
      to assess total energy expenditure. Patients wore the SenseWear ArmbandTM on
      their right arm continuously every day for 1 week. RESULTS: Total energy
      expenditure (<300 kcal/day), number of steps (<1500/day), physical-activity
      duration (<130 min/day) and active energy expenditure/day (<300 kcal) were all
      significantly lower (P<0.05) in patients with T2DM. These measures were inversely
      correlated with BMI, and remained significant after adjusting for age, gender,
      employment status and the presence of diabetes. CONCLUSION: Outpatients with T2DM
      have lower physical-activity levels than their matched controls, a characteristic
      that is related to their higher BMI.

PMID- 23159130
TI  - Screening of cardiovascular autonomic neuropathy in patients with diabetes using
      non-invasive quick and simple assessment of sudomotor function.
AB  - AIM: Cardiovascular autonomic neuropathy (CAN) is a common but often overlooked
      complication of diabetes. Sympathetic C-fibers innervating sweat glands can be
      impaired early on in patients with diabetes. In this study, SUDOSCAN, a new non
      invasive device that assesses sudomotor function was compared to methods
      generally used for the investigation of CAN. PATIENTS: A total of 232 patients
      with diabetes were measured for heart rate variability (HRV) at rest and during
      moderate activity. Time and frequency domain analysis techniques, including
      measurement of the low-frequency (LF) domain component, were assessed during HRV
      testing. Ewing tests, as recommended by the French Health Authority, were also
      done. Electrochemical sweat conductance (ESC) was measured on the hands and feet,
      and a risk-score was calculated. RESULTS: Using two abnormal Ewing tests as a
      reference for the area under the curve (AUC) of the receiver operating
      characteristics (ROC) curve for SUDOSCAN, the risk-score was 0.74, with a
      sensitivity of 92% and specificity of 49% for a risk-score cut-off value of 35%.
      For the ROC curve analysis using the LF power component during moderate activity
      at a threshold of 90 ms(2) (first quartile) as reference, the AUC was higher for
      the SUDOSCAN risk-score (0.77) compared with the standard Ewing tests [E:I ratio
      (0.62), 30:15 ratio (0.76) and blood pressure change on standing (0.55)]. Using a
      cut-off value of 35%, risk-score sensitivity and specificity were 88 and 54%,
      respectively. CONCLUSION: SUDOSCAN, which allows quick quantitative assessment of
      sudomotor function, may be used for early screening of CAN in everyday clinical
      practice before resorting to the more sophisticated and specific, but ultimately
      more time-consuming, Ewing tests.

PMID- 23159131
TI  - Insulin use and cancer risk in patients with type 2 diabetes: a systematic review
      and meta-analysis of observational studies.
AB  - AIMS: To determine whether data from observational studies supports the
      hypothesis of an increased risk of overall and site-specific cancer among
      individuals with diabetes using exogenous insulin therapies. METHODS: We
      conducted a comprehensive search of nine key biomedical databases for all years
      up to December 2011, restricted to the English language. Data from cohort and
      nested case-control studies were included in random effects meta-analyses of site
      specific and overall cancer incidence comparing ever use and new use of: (1)
      insulin to no insulin and; (2) insulin glargine to other insulins. RESULTS: The
      search yielded 3052 unique citations, of which 19 were selected for inclusion,
      representing data for 1,332,120 people and 41,947 cancers. Pancreatic cancer risk
      was increased among new users of insulin (RR: 3.18, 95%CI: 3.27-3.71, I(2)=32%).
      New use of insulin glargine was associated with an increased risk of pancreatic
      cancer (RR: 1.63, 95%CI: 1.05-2.51, I(2)=0%) and prostate cancers (RR: 2.68,
      95%CI: 1.50-4.79, I(2)=0%) but a decreased risk of colorectal cancer (RR: 0.78,
      95%CI: 0.64-0.94, I(2)=15%). CONCLUSION: New use of insulin or insulin glargine
      was associated with an increased risk of pancreatic cancer, possibly due to
      reverse causality. New use of insulin glargine was associated with a decreased
      risk of colorectal cancer but an increased risk of prostate cancer. Our results
      should be interpreted with caution due to limitations of included studies.

PMID- 23159132
TI  - Cerebral desaturation events in the intensive care unit following cardiac
      surgery.
AB  - PURPOSE: Patients may be at high risk for hemodynamic instability in the early
      postoperative period, with subsequent poor cerebral perfusion and the development
      of postoperative cerebral oxygen desaturation events (CDEs). Intraoperative CDEs
      have been associated with postoperative adverse events. However, none of these
      studies examined the incidence of early postoperative cerebral desaturations.
      This study was designed to identify the incidence of CDEs (defined as a decrease
      in SctO2 to less than 60% for at least 60 seconds) in the immediate postoperative
      period following cardiac surgery. METHODS: Fifty-three moderate to high-risk
      patients undergoing elective cardiac surgery were enrolled in this observational
      study. Cerebral oximeter monitors were placed on all patients prior to induction
      of anesthesia and remained in place for 6 hours or until the patients were
      extubated postoperatively, whichever occurred first. Data were recorded from the
      cerebral oximeter, physiologic monitor and ventilator during the study period.
      Data were analyzed to identify the incidence of early postoperative CDEs, as well
      as association with subsequent clinical events. RESULTS: The incidence of early
      postoperative CDEs was 53%. Sixty-four percent of these CDEs lasted for more than
      1 hour. Patients with postoperative CDEs were more likely to have had
      intraoperative CDEs (P< 0.0001). Five out of 28 patients who experienced CDEs in
      the intensive care unit died while none of the patients without postoperative
      CDEs died (P = .053). CONCLUSION: A high incidence of CDEs (53%) was found in the
      early post-cardiac surgery period. Larger studies are needed to determine whether
      postoperative CDEs are correlated with various physiologic events or are
      associated with adverse patient outcomes.

PMID- 23159133
TI  - Cardiac output responses in a flow-driven protocol of resuscitation following
      cardiac surgery.
AB  - OBJECTIVE: Determine the role of cardiac output and central venous pressure (CVP)
      measurements in the clinical decisions that were based on the algorithm used in a
      randomized trial that compared a colloid to a crystalloid solution in the
      management of patients early after cardiac surgery (FACS trial, NCT00337805, Crit
      Care Med 2010; 38:2117). METHODS: We analyzed the changes in CVP and cardiac
      index (CI) in 729 fluid challenges from the FACS trial in which 119 patients were
      randomized to colloid and 118 to crystalloid boluses in a flow-based protocol. A
      fluid challenge was defined as being positive if CI increased by >= 0.3 L/min(
      1)m(-2) and negative if CI increased by <0.3 L/min(-1)m(-2) but CVP increased by
      >= 2 mmHg. RESULTS: As defined in the protocol, 26% of boluses were given for a
      low CI (<2.2 L/min(-1)m(-2)). CI did not increase in 20% of boluses despite an
      adequate increase in CVP; in the protocol this meant that further volume boluses
      were not given. In another 34% of boluses in which CI did not increase, CVP
      increased by < 2 mmHg, which meant that volume responsiveness could not be ruled
      out and another bolus was indicated. 43% of the boluses were given for
      hypotension, but surprisingly in 90% of these instances, CI was in the acceptable
      range indicating that the low arterial pressure was due to decreased systemic
      vascular resistance. CONCLUSION: Measurement of cardiac output and CVP
      significantly influenced clinical decisions in the FACS algorithm.

PMID- 23159134
TI  - Impact of serum C-reactive protein measurements in the first 2 days on the 30-day
      mortality in hospitalized patients with severe community-acquired pneumonia: a
      cohort study.
AB  - INTRODUCTION: The purpose of the study is to evaluate the impact of daily
      consecutive measurements of C-reactive protein (CRP) in the initial 2 days of
      hospitalization on the 30-day all-cause mortality in patients with severe
      community-acquired pneumonia (CAP). METHODS: We used 4 different thresholds of
      fractional decrease (FD) in CRP at the second day of admission (CRP2) of 25%,
      30%, 40%, and 60%. In addition, we studied the association of each of these
      thresholds with the 30-day all-cause mortality. RESULTS: The mean age was 64 +/-
      20; males, 59%. The 30-day mortality rate was 18% (20/111). The mean serum CRP
      levels at the first day of all study group and CRP2 were 203 +/- 98 vs 146 +/- 92
      mg/L, respectively, P = .05. The mean FD in CRP2 levels among the survivors was
      33 %, whereas among the nonsurvivors, was 7%, P < .001. Multiple regression
      analysis revealed that FD less than 25% in CRP2 was associated with 30-day all
      cause mortality, odds ratio of 3.07 (95% confidence interval, 2.84-5.03), P =
      .002, compared with those with FD more than 25% in CRP2. CONCLUSIONS: Fractional
      decrease less than 25% in CRP levels at the second day was significantly
      associated with 30-day all-cause mortality in hospitalized patients with severe
      CAP.

PMID- 23159135
TI  - A bedside communication tool did not improve the alignment of a multidisciplinary
      team's goals for intensive care unit patients.
AB  - PURPOSE: Establishing well-understood daily patient care goals should improve
      healthcare team (HCT) communication, reduce errors, and improve patient outcomes.
      The purpose of this study was to test the hypothesis that implementation of a
      daily goals "Door Communication Card" (DCC) would improve goal alignment between
      members of the HCT. METHODS: As part of a process improvement project, HCT
      members listed their top care goals for a patient on a given day. After initial
      data collection, DCCs were placed on patients' doors. Anyone was allowed to write
      on the card, but the "official" daily goals were recorded during
      multidisciplinary rounds. One month after introduction of the DCC, HCT members
      were re-queried about their patients' care goals. Three reviewers independently
      compared goals and assessed their alignment before and after implementation of
      the DCC. We collected goals over a 4-month period and selected 5 random days
      before and after intervention for assessment. RESULTS: The goal alignment among
      HCT members was low before and did not improve after intervention (Attending-to
      Nurse 55% vs 38%, P = .02; Attending-to-Resident 60% vs 54%, P = .43; Attending
      to-Primary 35% vs 28%, P = .45; Nurse-to-Attending 52% vs 36%, P = .03; Nurse-to
      Resident 55% vs 38%, P = .04; Nurse-to-Primary 37% vs 27%, P = .36; Resident-to
      Attending 59% vs 54%, P = .4; Resident-to-Nurse 56% vs 40%, P = .05; Resident-to
      Primary 36% vs 24%, P = .16; Primary-to-Attending 34% vs 42%, P = .44; Primary-to
      Nurse 42% vs 35%, P = .6; Primary-to-Resident 32% vs 34%, P = .8). CONCLUSIONS:
      Alignment of daily patient care goals among HCT members is low overall and did
      not improve after implementing a DCC available to all team members. Further study
      to elucidate the mechanism by which daily goals forms improve patient care is
      required.

PMID- 23159136
TI  - Antipyretic therapy in febrile critically ill adults: A systematic review and
      meta-analysis.
AB  - PURPOSE: To determine whether fever control with antipyretic therapy effects the
      mortality of febrile critically ill adults. METHODS: Systematic review using
      MEDLINE, EMBASE, Cochrane Central Register for Controlled Trials, CINAHL, Google
      Scholar, and 2 clinical trial registries from inception to April 2012. Randomized
      clinical trials comparing treatment of fever with no treatment or comparing
      different thresholds for fever control in adults without acute neurological
      injury admitted to intensive care units (ICUs) were selected for review. The
      effect of fever control on all-cause ICU-mortality was determined using a random
      effects meta-analysis. RESULTS: Five randomized clinical trials in 399 patients
      were included. The temperature threshold for treatment in the intervention group
      was commonly 38.3 degrees C to 38.5 degrees C, whereas it was typically 40.0
      degrees C for controls. Four studies used physical measures and 3 used
      pharmacologic measures for temperature control. There was no significant
      heterogeneity among the included studies (I(2) = 12.5%, P = .3). Fever control
      did not significantly effect ICU mortality with a pooled risk ratio of 0.98 (95%
      confidence interval 0.58-1.63, P = .9). CONCLUSIONS: This meta-analysis found no
      evidence that fever treatment influences mortality in critically ill adults
      without acute neurological injury. However, studies were underpowered to detect
      clinically important differences.

PMID- 23159137
TI  - Risk of in-hospital mortality identified according to the typology of patients
      with acute heart failure: classification tree analysis on data from the Acute
      Heart Failure Database-Main registry.
AB  - PURPOSE: The purposes of this study are to identify the strongest clinical
      parameters in relation to in-hospital mortality, which are available in the
      earliest phase of the hospitalization of patients, and to create an easy tool for
      the early identification of patients at risk. MATERIALS AND METHODS: The
      classification and regression tree analysis was applied to data from the Acute
      Heart Failure Database-Main registry comprising patients admitted to specialized
      cardiology centers with all syndromes of acute heart failure. The classification
      model was built on derivation cohort (n = 2543) and evaluated on validation
      cohort (n = 1387). RESULTS: The classification tree stratifies patients according
      to the presence of cardiogenic shock (CS), the level of creatinine, and the
      systolic blood pressure (SBP) at admission into the 5 risk groups with in
      hospital mortality ranging from 2.8% to 66.2%. Patients without CS and creatinine
      level of 155 MUmol/L or less were classified into very-low-risk group; patients
      without CS, creatinine level greater than 155 MUmol/L, and SBP greater than 103
      mm Hg, into low-risk group, whereas patients without CS, creatinine level greater
      than 155 MUmol/L, and SBP of 103 mm Hg or lower, into intermediate-risk group.
      The high-risk group patients had CS and creatinine of 140 MUmol/L or less;
      patients with CS and creatinine level greater than 140 MUmol/L belong to very
      high-risk group. The area under receiver operating characteristic curve was 0.823
      and 0.832, and the value of Brier's score was estimated on level 0.091 and 0.084,
      for the derivation and the validation cohort, respectively. CONCLUSIONS: The
      presented classification model effectively stratified patients with all syndromes
      of acute heart failure into in-hospital mortality risk groups and might be of
      advantage for clinical practice.

PMID- 23159138
TI  - Delirium assessment using Confusion Assessment Method for the Intensive Care Unit
      in Chinese critically ill patients.
AB  - PURPOSE: The aim of this study was to provide a method for delirium evaluation in
      simplified Chinese for patients speaking this language via validation of a
      translation of the Confusion Assessment Method for the Intensive Care Unit (CAM
      ICU). MATERIALS AND METHODS: Two phases were conducted including initial
      reliability testing (phase I) of the Attention Screening Exam (ASE) followed by
      reliability and validity testing of the CAM-ICU (phase II). To analyze the
      reliability of the ASE, each patient was assessed sequentially by ASE Visual and
      ASE Auditory. The patients were assessed by 2 nurse investigators using CAM-ICU
      and 1 neurologist using Diagnostic and Statistical Manual of Mental Disorders,
      Fourth Edition separately within 2 hours in the second phase. RESULTS: We found
      that the agreement between ASE Visual and ASE Auditory was high (kappa = 0.83, P
      < .01, respectively). The educational level of the patients influenced the
      results of the inattention assessment, with the lower educational level of the
      patient yielding lower agreement on ASE. Even still, the kappa consistencies were
      all above 0.61. The sensitivities of CAM-ICU were 91.8% and 93.4%, and the
      specificities were 90.8%and 87.7%, respectively. The interrater reliability of 2
      nurse investigators was very high, with kappa coefficient of 0.92 (P < .001).
      CONCLUSIONS: This study affirmed the validity and reliability against reference
      raters using the Diagnostic and Statistical Manual of Mental Disorders, Fourth
      Edition of a brief nursing-conducted method of diagnosing delirium in ICU
      patients who speak simplified Chinese using the CAM-ICU.

PMID- 23159139
TI  - Contributions of tele-intensive care unit (Tele-ICU) technology to quality of
      care and patient safety.
AB  - The deployment of remote monitoring of intensive care unit (ICU) patients, known
      as tele-ICU technology, promotes the efficient use of critical care resources.
      Although tele-ICU use has spread rapidly, the benefits vary widely among studies,
      and little is known about the specific characteristics of tele-ICU that provide
      benefits to patient care. The purpose of this study was to identify aspects of
      tele-ICU that contribute, whether positively or negatively, to care processes and
      patient outcomes. This study was not aimed at evaluating the impact of tele-ICU
      on care outcomes. We conducted a qualitative study using semistructured
      interviews. Sixty-one tele-ICU staff from 5 tele-ICUs participated in the study.
      We performed inductive content analysis and coded 722 pieces of text into 19
      positive and 9 negative/neutral tele-ICU contributions to care processes and
      patient outcomes. We found that availability of extra resources can reduce on
      mortality and length of stay, that a tele-ICU could serve as a quality trigger to
      improve evidence-based medicine compliance, that tele-ICU can support medication
      management and improve medication safety, and that tele-ICU software alerts and
      monitoring by camera can help reduce the risk of patient falls and extubations.
      We also found that tele-ICU physicians can make poor care decisions leading to
      medication errors if they lack patient-related information. Moreover, the tele
      ICU has no impact on patient care processes and outcomes when the technology is
      not accepted and used by ICU staff.

PMID- 23159140
TI  - A conceptual approach to improving care in pandemics and beyond: severe lung
      injury centers.
AB  - The events of the 2009 influenza pandemic sparked discussion regarding the need
      to optimize delivery of care to those most severely ill. We propose in this
      conceptual study that a tiered regionalization care system be instituted for
      patients with severe acute respiratory distress syndrome. Such system would be a
      component of national pandemic plans and could also be used in day-to-day
      operations.

PMID- 23159141
TI  - Cerebral herniation associated with central venous catheter insertion: risk
      assessment.
AB  - PURPOSE: Central venous catheters (CVCs) are often necessary to treat acute brain
      injured patients. Four cases of cerebral herniation immediately following central
      venous catheterization were the impetus for an investigation of clinical and
      radiologic parameters associated with this complication. MATERIALS AND METHODS:
      This is a case series of 4 consecutive patients who experienced clinical cerebral
      herniation immediately following CVC placement in Trendelenburg or supine
      position. Clinical and computed tomography imaging findings were reviewed.
      RESULTS: All 4 patients developed new-onset clinical signs of cerebral herniation
      (unilateral or fixed dilated pupil and Glasgow Coma Scale [GCS], 3) within 30
      minutes of the procedure. All had radiographic signs of Sylvian fissure and/or
      basal cistern effacement on the preceding computed tomographic scan secondary to
      unilateral or bilateral mass lesions. Preprocedure GCS was 8 or more in all
      cases. Herniation was medically reversed in 3 of 4 patients, and 1 patient died
      of progressive brainstem ischemia. CONCLUSIONS: Trendelenburg and even flat
      position during CVC placement can increase intracranial pressure leading to
      cerebral herniation in patients with significant intracranial mass effect.
      Careful review of neuroimaging for signs of impending herniation before inserting
      CVCs and choosing an alternative treatment plan in these cases may avoid this
      potentially underreported complication.

PMID- 23159142
TI  - A comparison of the rapid shallow breathing index and complexity measures during
      spontaneous breathing trials after cardiac surgery.
AB  - PURPOSE: Extubation failure is associated with worse outcomes. Physicians use
      respiratory parameters to help them to decide to extubate or not. The purpose of
      this study is to determine if novel measures of respiratory physiology such as
      complexity and variability can identify patients who will tolerate extubation.
      METHODS: Eighty-three patients who required reinstitution of mechanical
      ventilation after extubation (Extub-Fail) were matched to 83 patients who
      successfully tolerated extubation (Extub-Success) and to 83 who failed a
      spontaneous breathing trial (SBT-Fail). Patients were compared using interbreath
      intervals and tidal volumes using means, SDs, measures of complexity, spikiness,
      and rapid shallow breathing index (RSBI). RESULTS: From SBT-Fail to Extub-Fail to
      Extub-Success, the interbreath intervals progressively lengthened (mean +/- SD,
      2.2 seconds +/- 0.6 vs 2.5 +/- 0.6 vs 2.7 +/- 0.8; P < .001), became more
      variable (mean +/- SD, 0.57 +/- 0.13 vs 0.62 +/- 0.21 vs 0.66 +/- 0.23; P =
      .012), and became more complex. Complexity as measured by approximate and sample
      entropy was greater in the Extub-Success group than in the SBT-Fail group.
      Patients who were in the SBT-Fail group had a higher RSBI than did either of the
      extubated groups, but there was no difference in RSBI between Extub-Success and
      Extub-Fail. CONCLUSIONS: Patients who successfully tolerate extubation have
      longer interbreath interval with greater complexity and variability of that
      series. Although the V(T) was similar between the Extub-Success and the SBT-Fail
      groups, the Extub-Success group had greater long-term complexity with no
      difference in short-term complexity. This implies that the respiratory
      controllers are differently impacted in patients tolerating or not tolerating
      extubation.

PMID- 23159143
TI  - Motivation and job satisfaction of Tele-ICU nurses.
AB  - INTRODUCTION: Although the first tele-ICU has been in existence for more than 12
      years, little is known about the work of tele-ICU nurses. This study examines
      sources of motivation and satisfaction of tele-ICU nurses. METHODS: A total of 50
      nurses in 5 tele-ICUs were interviewed about reasons for working as a tele-ICU
      nurse and sources of satisfaction and dissatisfaction in their job. RESULTS:
      Nurses have different motivations to work in the tele-ICU, including the
      challenges and opportunities for new learning that occur while interacting with
      clinicians in the tele-ICU and the various ICUs being monitored. Tele-ICU nurses
      also appreciate the opportunities for teamwork with tele-ICU physicians and
      nurses. The relationship and interactions with the ICUs is sometimes mentioned as
      a dissatisfier. Some nurses miss being physically at the bedside, as well as
      interacting with patients and families. CONCLUSION: Most tele-ICU nurses are
      satisfied with their job. They like the challenge in their work and the
      opportunity to learn. For some nurses, the transition from a bedside caregiver to
      an information manager can be difficult. Other nurses have found a balance by
      working part-time in the tele-ICU and part-time in the ICU.

PMID- 23159145
TI  - Focusing on the basic principles of dialysis to optimize regional citrate
      anticoagulation.

PMID- 23159144
TI  - Urine biochemistry in septic and non-septic acute kidney injury: a prospective
      observational study.
AB  - PURPOSE: Determine whether there are unique patterns to the urine biochemistry
      profile in septic compared with non-septic acute kidney injury (AKI) and whether
      urinary biochemistry predicts worsening AKI, need for renal replacement therapy
      and mortality. MATERIALS AND METHODS: Prospective cohort study of critically ill
      patients with septic and non-septic AKI, defined by the RIFLE (Risk, Injury,
      Failure, Loss, End-Stage) criteria. Urine biochemistry parameters were compared
      between septic and non-septic AKI and were correlated with neutrophil gelatinase
      associated lipocalin (NGAL), worsening AKI, renal replacement therapy (RRT), and
      mortality. RESULTS: Eighty-three patients were enrolled, 43 (51.8%) with sepsis.
      RIFLE class was not different between groups (P = .43). Urine sodium (UNa) <20
      mmol/L, fractional excretion of sodium (FeNa) <1%, and fractional excretion of
      urea (FeU) <35% were observed in 25.3%, 57.8%, and 33.7%, respectively. Septic
      AKI had lower UNa compared with non-septic AKI (P = .04). There were no
      differences in FeNa or FeU between groups. Urine NGAL was higher for FeNa >= 1%
      compared to FeNa<1% (177.4 ng/mL [31.9-956.5] vs 48.0 ng/mL [21.1-232.4], P =
      .04). FeNa showed low correlation with urine NGAL (P = .05) and plasma NGAL (P =
      .14). There was poor correlation between FeU and urine NGAL (P = .70) or plasma
      NGAL (P = .41). UNa, FeNa, and FeU showed poor discrimination for worsening AKI,
      RRT and mortality. CONCLUSION: Urine biochemical profiles do not discriminate
      septic and non-septic AKI. UNa, FeNa, and FeU do not reliably predict biomarker
      release, worsening AKI, RRT or mortality. These data imply limited utility for
      these measures in clinical practice in critically ill patients with AKI.

PMID- 23159146
TI  - Consecutive thrombelastography clot strength profiles in patients with severe
      sepsis and their association with 28-day mortality: a prospective study.
AB  - PURPOSE: The aim of this study was to assess associations between consecutive
      thrombelastography (TEG) profiles and standard coagulation tests and disease
      severity and mortality in patients with severe sepsis. MATERIALS AND METHODS:
      This was a prospective observational study of adults with severe sepsis admitted
      to the intensive care unit (ICU). Clinical scores/variables, infection, TEG,
      biochemistry, therapy, and overall mortality were recorded. RESULTS: Fifty
      patients (60% men, median age 62 years, 28-day mortality 24%) were included. At
      admission, 22%, 48%, and 30% had a hypocoagulable, normocoagulable, and
      hypercoagulable TEG clot strength (maximum amplitude [MA]), respectively.
      Hypocoagulable patients had higher Sequential Organ Failure Assessment and
      disseminated intravascular coagulation scores compared with hypercoagulable
      patients and higher 28-day mortality compared with normocoagulable patients (all
      P < .05). Most patients (73%-91%) displayed a TEG MA comparable with the
      admission profile during the initial 4 ICU days or until death/discharge.
      Patients progressing to hypocoagulable MA had a high early mortality (80%) and
      hypocoagulable MA independently predicted 28-day mortality (adjusted odds ratio,
      4.29 [95% confidence interval, 1.35-13.65], P = .014). In hypocoagulable and
      hypercoagulable patients, only fibrinogen (P = .041 and P < .001, respectively)
      contributed independently to clot strength, whereas both platelets (P < .001) and
      fibrinogen (P < .001) contributed independently to clot strength in
      normocoagulable patients. CONCLUSIONS: The ICU admission TEG MA remained constant
      for several days in patients with severe sepsis and hypocoagulable MA
      independently predicted 28-day mortality.

PMID- 23159147
TI  - Optimization of a small intestinal segment perfusion model for heat-stable
      enterotoxin A induced secretion in pigs.
AB  - Enterotoxigenic Escherichia coli (ETEC) are a major cause of infectious diarrhea
      both in human and pigs. After ingestion of contaminated food or water, ETEC
      bacteria colonize the small intestine where they produce heat-labile (LT) and/or
      heat-stable (ST) enterotoxins, which induce watery diarrhea. We investigated the
      possibility of eliciting STa-induced secretion in jejunal segments of
      anesthetized pigs using a small-intestinal segment perfusion (SISP) model. Five
      consecutive mid-jejunal segments of anaesthetized piglets were perfused for 6h
      with different concentrations of STa in a physiologic salt solution. Changes in
      intestinal net fluid absorption were measured. From the results we could conclude
      that the STa response was dose-dependent and that continuous perfusion with 50 nM
      of STa or more was required to reduce net absorption. This concentration was
      sufficient to reduce net absorption compared to control segments in 12 out of 14
      piglets. STa-induced responses however showed relative high variation between
      different jejunal segments of one pig, similar to the inter-segment variation
      seen in control animals where segments were perfused with physiologic salt
      solution. These results indicate that more optimization is required before this
      model could be used to test compounds that could interfere with the STa-induced
      fluid secretion.

PMID- 23159148
TI  - Open reduction of irreducible posterolateral rotary knee dislocation without
      sectioning of incarcerated vastus medialis: a case report with video
      illustration.
AB  - Traumatic knee joint dislocations are relatively rare. Most of knee dislocations
      are reduced by closed manipulation. However occasionally, especially in the case
      of soft tissue incarceration, closed reduction may not be possible and open
      reduction is mandatory. This report introduces a case of irreducible
      posterolateral rotary knee dislocation with interposition of vastus medialis
      treated through two-staged operations. In this report, we included preoperative
      magnetic resonance images (MRI), detailed intraoperative descriptions with
      photographs and video illustration that show the status of an injured knee joint
      and the effectiveness of the treatment. 

PMID- 23159150
TI  - Ensuring face validity in patient-related outcome scores--a matter of content.
AB  - BACKGROUND: Patient reported outcome (PRO) questionnaires are increasingly used
      to measure treatment effect in patients with knee pathology. PROs commonly used
      to assess outcome in patients with knee conditions can be generic, knee-specific,
      or condition-specific. Most PROs have been created based on clinician-based
      consensus and are not patient-centered. Items (questions plus their response
      options) in PROs can be generated by clinicians or through patient interviews.
      Items created by clinicians possess face validity. The objective of this study
      was to find all existing PRO items with potentially relevant content for patients
      with knee pathology. METHODS: An exhaustive literature search was conducted for
      PRO questionnaires in English, German, and Scandinavian languages used to assess
      outcome in patients with knee pathology. The items from the collected PROs were
      assessed for content redundancy and item reduction was carried out to isolate
      items of unique content. These items were grouped into one of the components of
      the ICF classification system. RESULTS: Thirty-one PROs used for assessment of
      patients with knee problems were identified, yielding 539 items. Approximately
      70% of these items consisted of redundant content matter. The item pool was
      reduced to a pool of 157 items. CONCLUSION: The search yielded 157 items of
      unique content. CLINICAL RELEVANCE: The identified items can be used to build
      condition-specific PRO questionnaires for patients with knee pathology.

PMID- 23159149
TI  - Predictors of functional outcome after revision total knee arthroplasty following
      aseptic failure.
AB  - BACKGROUND: There are a limited number of studies related to quality of life and
      functional outcome after revision total knee arthroplasty (TKA). The present
      study aimed to identify predictors of functional outcome after revision TKA for
      aseptic failure. METHODS: One hundred seventy-five patients with mean age of 66.6
      years (range, 35-88) who underwent revision TKA for aseptic failure at our
      institute from 2003 to 2007 were identified. Short-form 36 (SF-36), Western
      Ontario and McMaster Osteoarthritis Index (WOMAC) and Knee Society Scores (KSS)
      collected preoperatively and at 2 years follow up were evaluated. Univariate and
      multivariate analyses were performed to determine predictors of functional
      outcome in studied patients. RESULTS: Both physical and mental dimensions of SF
      36, pain, functional, and stiffness subscales of WOMAC and both functional and
      clinical scores of KSS improved significantly after revision TKA (p<0.001). In
      the multivariate analysis, male gender, a lower Charlson comorbidity index, and
      higher preoperative functional KSS were predictors of higher functional KSS at 2
      years after revision. Lower preoperative pain and higher clinical KSS were
      predictors of better outcome as measured by pain scale of WOMAC. Body mass index
      (BMI) and preoperative clinical KSS were significant predictors of function and
      stiffness as measured by WOMAC. CONCLUSIONS: BMI is a modifiable predictor of
      functional outcome after revision TKA. Moreover, patients with higher
      preoperative functional scores appear to have better postoperative function.
      LEVEL OF EVIDENCE: Level II.

PMID- 23159151
TI  - Mortality and perioperative complications after unicompartmental knee
      arthroplasty.
AB  - AIM OF STUDY: Unicompartmental knee arthroplasty (UKA) has been increasingly
      utilized over the past decade secondary to favorable reports of better range of
      motion, higher activity levels, and increased patient satisfaction compared with
      total knee arthroplasty (TKA). The aim of this study was to determine the 90-day
      incidence of perioperative complications and mortality of patients undergoing
      UKA. METHODS: One thousand consecutive UKA in 828 patients were retrospectively
      reviewed. A retrospective review was performed to evaluate 90-day perioperative
      complication and mortality rates. RESULTS: There were zero deaths during the
      study period. Twelve percent of surgeries were complicated by variances within
      the 90-day postoperative period. There was one deep venous thrombosis (0.1%) and
      no pulmonary emboli. Cardiovascular complications were infrequent. Three patients
      had a myocardial infarction (0.31%), one developed congestive heart failure
      (0.1%), one angina (0.1%), and three had arrhythmias (0.31%). Secondary
      procedures were performed in 15 patients during the follow-up period: seven were
      manipulations under anesthesia for arthrofibrosis, one was an arthroscopic
      removal of retained cement, one arthroscopic removal of a drain, one repeat wound
      closure after a dehiscence secondary to a fall, one open reduction internal
      fixation for a supracondylar femur fracture, three irrigation and debridement
      procedures for an aseptic hematoma, and one radical debridement with later
      successful conversion to a total knee arthroplasty for a periprosthetic
      infection. CONCLUSION: This study supports the notion that UKA is a safe
      procedure that is associated with a low rate of mortality and serious post
      operative complications.

PMID- 23159152
TI  - Fracture of an Oxford femoral component: a case report.
AB  - Component fracture is a rare complication after knee replacement, especially in
      contemporary designs. We report the first case of a fractured femoral component
      in a cemented Oxford unicondylar knee prosthesis, 9 years after its implantation.
      Factors leading to this rare kind of component failure are discussed. Revision
      should be warranted in cases of unicondylar femoral component loosening,
      eliminating the risk of component fracture, especially in obese patients.

PMID- 23159153
TI  - A minimally invasive postero-medial approach with suture anchors for isolated
      tibial avulsion fracture of the posterior cruciate ligament.
AB  - BACKGROUND AND PURPOSE: The optimal surgical treatment of isolated tibial
      avulsion fractures of the posterior cruciate ligament (PCL) remains
      controversial. The purpose of this study was to report preliminary results of a
      novel surgical approach to isolated PCL avulsion fractures by a minimally
      invasive postero-medial approach with suture anchors. PATIENTS AND METHODS:
      Outcomes were retrospectively analyzed in 16 patients with isolated tibial
      avulsion fractures of the PCL treated with this approach. RESULTS: Length of
      surgery ranged from 20 to 40 min (mean, 28 min). Patients were followed-up for 4
      to 36 months (mean, 18 months). X-rays showed that satisfactory reduction and
      bony healing was achieved in all cases. Excellent and good outcomes were reported
      by 15 and 1 patient respectively with the Lysholm score system. CONCLUSIONS: This
      minimally invasive postero-medial approach, with minimal but sufficient exposure
      and effective fixation, may be suitable for the treatment of isolated tibial
      avulsion fractures of the PCL. More detailed and longer follow up of these
      patients is needed before definitive conclusions on efficacy can be reached.

PMID- 23159154
TI  - YWHAE-FAM22 endometrial stromal sarcoma: diagnosis by reverse transcription
      polymerase chain reaction in formalin-fixed, paraffin-embedded tumor.
AB  - A subset of endometrial stromal sarcoma harbors t(10;17)(q23;p13), which results
      in the genetic fusion between YWHAE and 1 of 2 highly homologous FAM22 family
      members-FAM22A or FAM22B. In contrast to classic low-grade endometrial stromal
      sarcoma with JAZF1-SUZ12 fusions, YWHAE-FAM22 endometrial stromal sarcoma
      displays high-grade histologic features and is associated with more aggressive
      disease course. Ancillary fluorescence in situ hybridization assay demonstrating
      the presence of YWHAE rearrangement can be used to support the diagnosis, but the
      detection of fusion transcript would be the most definitive test. We describe
      here an optimized reverse transcription-polymerase chain reaction assay for
      detection of YWHAE-FAM22 fusion transcript in formalin-fixed and paraffin
      embedded tumor samples. We studied a series of 6 YWHAE-FAM22 endometrial stromal
      sarcomas, 7 JAZF-SUZ12 endometrial stromal sarcomas, 3 JAZF1-PHF1/EPC1-PHF1
      endometrial stromal sarcomas, 6 undifferentiated endometrial sarcomas, 4 uterine
      leiomyosarcomas, and 4 uterine adenosarcomas. All 6 YWHAE-FAM22 endometrial
      stromal sarcomas were confirmed by fluorescence in situ hybridization assay,
      whereas all non-YWHAE-FAM22 tumors were confirmed to lack YWHAE rearrangement by
      fluorescence in situ hybridization assay. The reverse transcription-polymerase
      chain reaction assay optimized for formalin-fixed and paraffin-embedded samples
      detected YWHAE-FAM22 fusion transcripts in all 6 YWHAE-FAM22 endometrial stromal
      sarcomas and none of the 24 non-YWHAE-FAM22 uterine sarcomas. These findings show
      that this reverse transcription-polymerase chain reaction assay is sensitive and
      specific for detection of YWHAE-FAM22 fusion transcript and can serve as a useful
      adjunct diagnostic assay to confirm the diagnosis of YWHAE-FAM22 endometrial
      stromal sarcoma in formalin-fixed and paraffin-embedded tumor samples.

PMID- 23159155
TI  - Different expression pattern and significance of p14ARF-Mdm2-p53 pathway and Bmi
      1 exist between gastric cardia and distal gastric adenocarcinoma.
AB  - Recent studies have suggested that adenocarcinoma of gastric cardia (GCA) is
      distinct from distal stomach, with different risk factors, tumor characteristics,
      and biological behavior. The aim of this study is to evaluate the possible
      difference in the expressions of p14ARF, Mdm2, p53, and Bmi-1 by
      immunohistochemical staining on paraffin-embedded tissues of gastric cardia
      adenocarcinoma (GCA; n = 74) and distal gastric adenocarcinoma (DGA; n = 41). The
      results showed that the percentage of p14ARF-negative expression, Mdm2
      overexpression, p53-positive expression, and p53 pathway abnormality (p14ARF(
      )/Mdm2(+)/p53(+)) were all significantly higher in GCA than those in DGA (P <
      .05). Further analysis showed that in GCA, the negative expression of p14ARF was
      significantly associated with poor differentiation, Mdm2 overexpression with
      tumor stage and lymph node metastasis, and positive p53 expression with tumor
      stage (P < .05), whereas in DGA, only Mdm2 overexpression was related with
      well/moderate differentiation (P < .05). Abnormality of the p53 pathway was
      significantly correlated with poorer differentiation only in GCA (P < .05). The
      positive expression of Bmi-1 in all cases of GCA and DGA was significantly higher
      than normal gastric mucosa epithelium, but no difference was found between GCA
      and DGA (P > .05). Thus, the results in this study confirmed that different
      expression pattern and clinicopathologic significance of the p14ARF-Mdm2-p53
      pathway did exist between GCA and DGA. The results further support the hypothesis
      that different mechanisms may be involved in the development and progression of
      adenocarcinoma from cardia and distal portion of stomach.

PMID- 23159156
TI  - Tumor budding score based on 10 high-power fields is a promising basis for a
      standardized prognostic scoring system in stage II colorectal cancer.
AB  - Tumor budding is recognized by the World Health Organization as an additional
      prognostic factor in colorectal cancer but remains unreported in diagnostic work
      due to the absence of a standardized scoring method. This study aims to assess
      the most prognostic and reproducible scoring systems for tumor budding in
      colorectal cancer. Tumor budding on pancytokeratin-stained whole tissue sections
      from 105 well-characterized stage II patients was scored by 3 observers using 7
      methods: Hase, Nakamura, Ueno, Wang (conventional and rapid method), densest high
      power field, and 10 densest high-power fields. The predictive value for
      clinicopathologic features, the prognostic significance, and interobserver
      variability of each scoring method was analyzed. Pancytokeratin staining allowed
      accurate evaluation of tumor buds. Interobserver agreement for 3 observers was
      excellent for densest high-power field (intraclass correlation coefficient, 0.83)
      and 10 densest high-power fields (intraclass correlation coefficient, 0.91).
      Agreement was moderate to substantial for the conventional Wang method (kappa =
      0.46-0.62) and moderate for the rapid method (kappa = 0.46-0.58). For Nakamura,
      moderate agreement (kappa = 0.41-0.52) was reached, whereas concordance was fair
      to moderate for Ueno (kappa = 0.39-0.56) and Hase (kappa = 0.29-0.51). The Hase,
      Ueno, densest high-power field, and 10 densest high-power field methods
      identified a significant association of tumor budding with tumor border
      configuration. In multivariate analysis, only tumor budding as evaluated in
      densest high-power field and 10 densest high-power fields had significant
      prognostic effects on patient survival (P < .01), with high prognostic accuracy
      over the full 10-year follow-up. Scoring tumor buds in 10 densest high-power
      fields is a promising method to identify stage II patients at high risk for
      recurrence in daily diagnostics; it is highly reproducible, accounts for
      heterogeneity, and has a strong predictive value for adverse outcome.

PMID- 23159157
TI  - Developing and evaluating complex interventions: the new Medical Research Council
      guidance.

PMID- 23159158
TI  - Effect of antioxidant supplementation on function and fertility of sex-sorted
      boar spermatozoa.
AB  - The goal of this study was to investigate the effects of antioxidant
      supplementation on the quality of flow cytometrically-sorted boar spermatozoa.
      The effects of ascorbic acid-2-glucoside (AA-2G) on the sex-sorting process were
      evaluated using a variety of concentrations. The effects of different
      antioxidants (AA-2G, l-glutathione, and vitamin E) on the viability and lifespan
      of boar spermatozoa were also compared during sorting. Furthermore, the effect of
      AA-2G on acrosome intactness, the capacitation ability of sorted boar spermatozoa
      and pregnancy efficiency after artificial insemination (AI) at different sorting
      to-insemination intervals were examined. Greater (P<0.05) percentages of motile
      spermatozoa and acrosome intactness and longer storage time periods were observed
      in the AA-2G-supplemented group when compared with the other antioxidant
      supplemented or control groups. At an AA-2G concentration of 0.068 mg/mL, the
      motility characteristics (i.e., straightness (STR), velocity according to the
      average path (VAP), and amplitude of the sperm head lateral displacement (ALH))
      of the sex-sorted boar spermatozoa were greater (P<0.05) than in those treated
      with other AA-2G concentrations. The capacitation rate of boar spermatozoa in the
      AA-2G-supplemented group was less (P<0.05) than that in the control group. After
      sorting-to-insemination interval of 10h, the pregnancy rates after AI with boar
      spermatozoa for the AA-2G-supplemented group were 59.25%, while the control group
      remains no sufficient quality semen. This study demonstrates that AA-2G
      supplementation can improve the quality of flow cytometrically sorted boar
      spermatozoa and that the optimal concentration of AA-2G for sorting is 0.068
      mg/mL.

PMID- 23159159
TI  - Maternal age >=45 years and maternal and perinatal outcomes: a review of the
      evidence.
AB  - OBJECTIVE: to examine the evidence in relation to very advanced maternal age
      (>=45 years) and maternal and perinatal outcomes in high-income countries.
      BACKGROUND: this review was conducted against a background of increasing
      fertility options for women aged >==45 years and rising birth rates among this
      group of women. METHODS: established health databases including SCOPUS, MEDLINE,
      CINAHL, EMBASE and Maternity and Infant Care were searched for journal papers,
      published 2001-2011, that examined very advanced maternal age (VAMA) and maternal
      and perinatal outcomes. Further searches were based on references found in
      located articles. Keywords included a search term for maternal age >=45 years
      (very advanced maternal age, pregnancy aged 45 years and older) and a search term
      for maternal complications (caesarian section, hypertension, pre-eclampsia,
      gestational diabetes) and/or adverse perinatal outcome (preterm birth, low birth
      weight, small for gestational age, stillbirth, perinatal death). Of 164 retrieved
      publications, 10 met inclusion criteria. DATA EXTRACTION: data were extracted and
      organised under the following headings: maternal age >=45 years; maternal
      characteristics such as parity and use of artificial reproductive technology
      (ART); and pre-existing maternal conditions, such as diabetes and hypertension.
      Additional headings included: gestational conditions, such as pre-eclampsia and
      gestational diabetes (GDM); and perinatal outcomes, including fetal/infant
      demise; gestational age and weight. Study quality was assessed by using the
      Critical Appraisal Skills Programme (CASP) guidelines. FINDINGS: this review
      produced three main findings: (1) increased rates of stillbirth, perinatal death,
      preterm birth and low birth weight among women >=45 years; (2) increased rates of
      pre-existing hypertension and pregnancy complications such as GDM, gestational
      hypertension (GH), pre-eclampsia and interventions such as caesarian section; and
      (3) a trend of favourable outcomes, even at extremely advanced maternal age (50
      65 years), for healthy women who had been screened to exclude pre-existing
      disease. KEY CONCLUSIONS: although there is strong evidence of an association
      between very advanced maternal age and adverse maternal and perinatal outcomes,
      the absolute rate of stillbirth/perinatal death remains low, at less than 10 per
      1000 births in most high-income countries. Therefore, although women in this age
      group encounter greater pregnancy risk, most will achieve a successful pregnancy
      outcome. Best outcomes appear to be linked to pre-existing maternal health, and
      pregnancy care at tertiary centres may also contribute. This information should
      be used to counsel women aged >=45 years who are contemplating pregnancy.

PMID- 23159160
TI  - Women's experiences of outpatient induction of labour with remote continuous
      monitoring.
AB  - OBJECTIVE: to gain insight into women's experiences and preferences for induction
      in the home as part of a trial investigating the feasibility and acceptability of
      outpatient induction of labour with remote monitoring. DESIGN: a qualitative
      study using semi-structured individual interviews. Interview transcripts were
      subjected to thematic analysis to identify the dominant themes regarding women's
      experiences of outpatient induction. SETTING: a large maternity hospital in the
      North West of England. PARTICIPANTS: fifteen women who participated in the main
      trial of outpatient induction of labour with remote continuous monitoring.
      FINDINGS: three main themes were identified; the need for women to 'labour within
      their comfort zone'; their desire to achieve 'the next best thing to a normal
      labour' and the importance of a 'virtual presence' to offer remote reassurance.
      CONCLUSIONS: women's preference for the outpatient setting of induction of labour
      is dominated by their need to labour within their comfort zone. Outpatient
      induction offered women the familiarity and freedom of the home environment, and
      the resulting physical and emotional comforts helped women cope better with their
      labour and improved their birth experiences. While remote monitoring offered some
      reassurance, women still depended on effective communication from hospital staff
      to provide the virtual presence of a health professional in the home.
      IMPLICATIONS: the combination of slow-release prostaglandin and a remote
      monitoring device may provide low risk women with an improved induction and
      labour experience. While ongoing studies continue to explore further the safety
      of interventions at home, this study has importantly considered women's views and
      confirmed that induction at home is not only acceptable to women but also that
      the outpatient experience is preferable to long inpatient inductions.

PMID- 23159161
TI  - The role of anxiety and other factors in predicting postnatal fatigue: from birth
      to 6 months.
AB  - OBJECTIVE: to explore the role of anxiety and other factors in predicting
      postnatal fatigue from birth to 6 months. DESIGN: a prospective longitudinal
      correlational survey design. SETTING: Canberra, Australian Capital Territory,
      Australia. PARTICIPANTS: 504 well women, 233 primipara and 271 multipara, aged 20
      40 years who gave birth during the study period. MEASUREMENT: the Postpartum
      Fatigue Scale, the State-Trait Anxiety Inventory, the Edinburgh Postnatal
      Depression Scale, and the Support Behavior Inventory were used to measure the
      relationship between the predictive factors and the intensity of fatigue at the
      various time points. FINDINGS: an explanatory model of fatigue development was
      applied to all participants, and then to primiparas and multiparas, explaining 27
      44% of the variance in fatigue from 1 to 24 weeks in the total sample (p>.001).
      State anxiety was a consistently strong predictor of fatigue intensity across
      time and group. KEY CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: the contribution
      that state anxiety made to the development of fatigue in this group of low risk
      women highlights the importance of assessing symptoms of anxiety in all
      childbearing women. Focusing on depressive symptoms limits the extent to which
      anxiety symptoms, which occur in parallel with depressive symptoms, are
      addressed. Anxiety is a normal response to the changes in roles and
      responsibilities that occur following birth. However the belief that all new
      mothers worry excessively and that anxiety is not as harmful as depression may
      have influenced the way midwives and maternal child health nurses view postnatal
      anxiety. Assessment of anxiety, and use of interventions such as cognitive and
      behavioural strategies and self-care practices, can be used to assist women to
      reduce anxiety levels.

PMID- 23159162
TI  - Preparing fathers for the transition to parenthood: recommendations for the
      content of antenatal education.
AB  - Fathers now provide more care for their babies and children than they have in the
      past, and a large body of evidence supports the important role that father
      involvement plays in determining child and family outcomes. Fathers have also
      become the primary source of informal support for most mothers and it is now
      customary for fathers to attend antenatal education in this supporting role.
      However, many fathers remain unprepared for their personal transition to
      parenthood and this has important implications for all of the family. Antenatal
      education is likely to be more effective for fathers when it addresses fathers'
      needs but the literature is unclear about what fathers need to know. This paper
      presents evidence-based recommendations for core subject matter to be addressed
      when preparing men for the important challenges of new fatherhood.

PMID- 23159163
TI  - Effects of repetitive movement on range of motion and stiffness around the
      neutral orientation of the human lumbar spine.
AB  - In loading experiments on the lumbar spine, typically three consecutive loading
      cycles are applied of which the third cycle is used for analysis. The aim of this
      study was to investigate whether the use of ten instead of three loading cycles
      reduces effects of viscoelastic behavior in the assessment of range of motion
      (ROM) and stiffness around the neutral orientation of the human lumbar spine. To
      this end, twelve cadaveric human lumbar spines (L1-L5) were obtained (mean age:
      76.9 years). Before testing, the spines were subjected to a compressive load of
      250 N for 1 h. To each spine, ten consecutive loading cycles were applied (-4 Nm
      to+4 Nm) in flexion and extension (FE), lateral bending (LB) and axial rotation
      (AR). The ROM and stiffness within the neutral zone were calculated per motion
      segment (L2-L3, L3-L4 or L4-L5) from load-displacement data. It was found that
      the ROM increased significantly (all p<0.001) in all directions after three (FE:
      0.07 degree/1.0%, LB: 0.08 degree/1.5%, and AR: 0.04 degree/1.5%) and after ten
      loading cycles (FE: 0.20 degree/2.9%, LB: 0.16 degree/3.3%, and AR: 0.09
      degree/3.3%). Stiffness was not significantly affected, but varied considerably
      over cycles. Although effects were small, assessment of the tenth cycle instead
      of the third cycle reduces viscoelastic effects in repeated measurements of ROM,
      because the spine is closer to a steady state condition, while averaging over
      loading cycles would improve the assessment of stiffness estimates.

PMID- 23159164
TI  - Interest of analyses of heart rate variability in the prevention of fatigue
      states in senior runners.
AB  - BACKGROUND: The use of heart rate variability (HRV) in the management of sport
      training is a practice which tends to spread, especially in order to prevent the
      occurrence of fatigue states. OBJECTIVES: To estimate the HRV parameters obtained
      using a heart rate recording, according to different exercise impacts, and to
      make the link with the appearance of subjective fatigue. METHODS: Ten senior
      runners, aged 51+/-5 years, were each monitored over a period of 12 weeks in
      different conditions: (i) after a resting period, (ii) after a day with training,
      (iii) after a day of competition and (iv) after a rest day. They also completed
      three questionnaires, to assess fatigue (SFMS), profile of mood states (POMS) and
      quality of sleep. RESULTS: The HRV indices (heart rate, LF (n.u.), HF (n.u.) and
      LF/HF) were significantly altered with the competitive impact, shifting toward a
      sympathetic predominance. After rest and recovery nights, the LF (n.u.) increased
      significantly with the competitive impact (62.1+/-15.2 and 66.9+/-11.6 vs. 76.0+/
      10.7; p<0.05 respectively) whereas the HF (n.u.) decreased significantly (37.9+/
      15.2 and 33.1+/-11.6 vs. 24.0+/-10.7; p<0.05 respectively). Positive correlations
      were found between fatigue and frequency domain indices and between fatigue and
      training impact. CONCLUSION: Autonomic nervous system modulation-fatigue
      relationships were significant, suggesting the potential use of HRV in follow-up
      and control of training. Furthermore, the addition of questionnaires constitutes
      complementary tools that allow to achieve a greater relevance and accuracy of the
      athletes' fitness and results.

PMID- 23159165
TI  - Highlights in basic autonomic neurosciences: remote ischaemic preconditioning as
      an autonomic reflex--a question of timing and circumstances?

PMID- 23159166
TI  - Examining the measurement properties of the Interdisciplinary Education
      Perception Scale (IEPS) in paramedic education.
AB  - BACKGROUND: Healthcare systems are continuing searching for alternative service
      delivery models while at the same time also promoting interprofessional practice
      and cooperation among workers. One scale that aims to measure interprofessional
      cooperation is the Interdisciplinary Education Perception Scale (IEPS), although
      limited psychometric testing on its validity and reliability has been carried
      out. Therefore the aim of this study was to investigate the dimensionality and
      internal consistency of the IEPS (suggested by McFadyen and colleagues) when
      completed by a group of paramedic undergraduates. METHODS: Data from the IEPS
      were analysed with a factor analysis using a Principal Axis Factoring (PAF) with
      Oblique Oblimin rotation. RESULTS: A total of (n=303) undergraduate paramedic
      students participated in the study who reported having positive attitudes towards
      interprofessional cooperation. Factor analysis of the 12-items revealed two
      factors with eigenvalues above 1, accounting for 53.85% of the total variance.
      Items with loadings greater than +/-.30, with the factor in question were used to
      describe the two factors: Cooperation and Teamwork, and Positivity. CONCLUSION:
      While data from this study produced a multi-dimensional scale with adequate
      eigenvalues and communalities, improvements to the scales internal consistency
      can be made with future data sets. The results from the IEPS suggest that
      undergraduate paramedics have positive regard towards interprofessional
      cooperation.

PMID- 23159168
TI  - TMD before and after correction of dentofacial deformities by orthodontic and
      orthognathic treatment.
AB  - The aims of the study were to investigate the alteration of temporomandibular
      disorders (TMD) after correction of dentofacial deformities by orthodontic
      treatment in conjunction with orthognathic surgery; and to compare the frequency
      of TMD in patients with dentofacial deformities with an age and gender matched
      control group. TMD were evaluated in 121 consecutive patients (treatment group),
      referred for orthognathic surgery, by a questionnaire and a clinical examination.
      18 months after treatment, 81% of the patients completed a follow-up examination.
      The control group comprised 56 age and gender matched subjects, of whom 68%
      presented for follow-up examination. TMD were diagnosed according to research
      diagnostic criteria for TMD. At baseline examination, the treatment group had a
      higher frequency of myofascial pain (P=.035) and arthralgia (P=.040) than the
      control group. At follow-up, the frequencies of myofascial pain, arthralgia and
      disc displacement had decreased in the treatment group (P=.050, P=.004, P=.041,
      respectively). The frequency of TMD was comparable in the two groups at follow
      up. Patients with dentofacial deformities, corrected by orthodontic treatment in
      conjunction with orthognathic surgery, seem to have a positive treatment outcome
      in respect of TMD pain.

PMID- 23159169
TI  - Clinical outcome and bone healing of implants placed with high insertion torque:
      12-month results from a multicenter controlled cohort study.
AB  - This study evaluated the clinical outcome and the crestal bone resorption of
      implants placed with high insertion torque (up to 80 N cm). 102 patients were
      treated with 156 tapered implants. 42 implants (control group) presented
      insertion torque between 30 and 45 N cm (mean=37.4 SD 8.2). 114 implants
      (experimental group) were placed with insertion torque between 50 and 80 N cm
      (mean=74.8 SD 7.9). All implants were early loaded after 2 months. Peri-implant
      marginal bone levels were assessed immediately after surgery, and at 6- and 12
      month follow up examinations. At the 12-month follow up all implants were
      clinically stable. After 12 months, patients in the experimental group lost an
      average of 0.41 mm (CI 95% 0.522; 0.263) of crestal bone compared with 0.45 mm
      (CI 95% 0.561; 0.286) for those in the control group. There were no significant
      differences between the two groups. No direct or inverse relationship was
      observed between the insertion torque values and crestal bone resorption. The
      results show that the use of high insertion torque (up to 80 N cm) did not
      prevent osseointegration and did not increase bone resorption around tapered
      implants early loaded up to 1 year after implant placement.

PMID- 23159167
TI  - Multiplicity-dependent activation of a serine protease-dependent cytomegalovirus
      associated programmed cell death pathway.
AB  - At a low MOI (<=0.01), cytomegalovirus-associated programmed cell death
      terminates productive infection via a pathway triggered by the mitochondrial
      serine protease HtrA2/Omi. This infected cell death is associated with late phase
      replication events naturally suppressed by the viral mitochondrial inhibitor of
      apoptosis (vMIA). Here, higher MOI (ranging from 0.1-3.0) triggers cell death
      earlier during infection independent of viral DNA synthesis. Thus, MOI-dependent
      activating signals early, at high MOI, or late, at low MOI, during replication
      promote serine protease-dependent death that is suppressed by vMIA. Treatment
      with an antioxidant targeting reactive oxygen species (ROS) or the serine
      protease inhibitor N-alpha-p-tosyl-L-lysine chloromethyl ketone (TLCK) delays
      cell death, and the combination has an additive impact. These studies identify
      serine proteases and ROS as important factors triggering programmed cell death
      induced by vMIA-deficient virus, and show that this death pathway occurs earlier
      and reduces viral yields as the MOI is increased.

PMID- 23159170
TI  - Reply to Dr. Yamamoto et al.'s letter.

PMID- 23159172
TI  - The basic science of hair biology: what are the causal mechanisms for the
      disordered hair follicle?
AB  - A hair disorder can be difficult to define, but patients are typically motivated
      to seek treatment when their hair growth patterns are significantly different
      from their cultural group or when growth patterns change significantly. The
      causes of hair disorders are many and varied, but fundamentally the disorder is a
      consequence of aberrant alterations of normal hair biology. The potential trigger
      factors for hair disorders can be attributed to inflammation, genetics, the
      environment, or hormones, of which the relative contributions vary for different
      diagnoses, between individuals, and over time. This article discusses the causal
      mechanisms for the disordered hair follicle.

PMID- 23159171
TI  - Targeting breast carcinoma with radioiodinated anti-HER2 Nanobody.
AB  - INTRODUCTION: With a molecular weight an order of magnitude lower than antibodies
      but possessing comparable affinities, Nanobodies (Nbs) are attractive as
      targeting agents for cancer diagnosis and therapy. An anti-HER2 Nb could be
      utilized to determine HER2 status in breast cancer patients prior to trastuzumab
      treatment. This provided motivation for the generation of HER2-specific 5F7GGC
      Nb, its radioiodination and evaluation for targeting HER2 expressing tumors.
      METHODS: 5F7GGC Nb was radioiodinated with 125I using Iodogen and with 131I using
      the residualizing agent N(E)-(3-[131I]iodobenzoyl)-Lys5-N(alpha)-maleimido-Gly1
      GEEEK ([131I]IB-Mal-D-GEEEK) used previously successfully with intact antibodies.
      Paired-label internalization assays using BT474M1 cells and tissue distribution
      experiments in athymic mice bearing BT474M1 xenografts were performed to compare
      the two labeled Nb preparations. RESULTS: The radiochemical yields for Iodogen
      and [131I]IB-Mal-D-GEEEK labeling were 83.6+/-5.0% (n=10) and 59.6+/-9.4% (n=15),
      respectively. The immunoreactivity of labeled proteins was preserved as confirmed
      by in vitro and in vivo binding to tumor cells. Biodistribution studies showed
      that Nb radiolabeled using [131I]IB-Mal-D-GEEEK, compared with the directly
      labeled Nb, had a higher tumor uptake (4.65+/-0.61% ID/g vs. 2.92+/-0.24% ID/g at
      8h), faster blood clearance, lower accumulation in non-target organs except
      kidneys, and as a result, higher concomitant tumor-to-blood and tumor-to-tissue
      ratios. CONCLUSIONS: Taken together, these results demonstrate that 5F7GGC anti
      HER2 Nb labeled with residualizing [131I]IB-Mal-D-GEEEK had better tumor
      targeting properties compared to the directly labeled Nb suggesting the potential
      utility of this Nb conjugate for SPECT (129I) and PET imaging (124I) of patients
      with HER2-expressing tumors.

PMID- 23159173
TI  - How to diagnose hair loss.
AB  - This review presents a systematic approach to the diagnosis of hair loss. An
      accurate diagnosis is based on history, clinical examination, laboratory tests,
      and scalp biopsy. Whether the hair loss is a cicatricial or noncicatricial
      alopecia guides one's history taking. After assessing the patient's global
      appearance, the hair and scalp are evaluated, aided by a hair pull, hair tug,
      Hair Card, and hair mount. Scalp biopsies can confirm a diagnosis and are
      essential in all cases of cicatricial alopecia. In all patients with hair loss a
      complete blood count, ferritin, thyroid stimulating hormone, and vitamin D 25OH
      should be ordered.

PMID- 23159174
TI  - Trichoscopy: how it may help the clinician.
AB  - Trichoscopy (or dermoscopy of hair and scalp) is an easy in-office technique that
      may be performed with a handheld dermoscope or a digital videodermoscopy system.
      This method is gaining increasing popularity, because it may be applied in
      differential diagnosis of multiple hair and scalp diseases. The focus of this
      article is application of trichoscopy in differential diagnosis of the most
      frequent hair and scalp diseases in dermatologic practice. Trichoscopy of genetic
      hair shaft abnormalities are briefly addressed. A new classification of
      perifollicular and interfollicular skin surface abnormalities is proposed.

PMID- 23159175
TI  - Histopathology of scarring and nonscarring hair loss.
AB  - This article reviews the histologic findings of alopecia, preceded by a brief
      discussion of biopsy and processing techniques, the normal follicular anatomy and
      cycle, and expected findings in transverse sections. Subtle histologic
      abnormalities will be missed unless the normal follicular anatomy and follicular
      cycle, when viewed in transverse sections, are understood.

PMID- 23159176
TI  - How to diagnose and treat medically women with excessive hair.
AB  - Excessive hair growth in women is common and due to a broad spectrum of causes.
      Management options comprise different pharmaceuticals, epilation methods, and
      aesthetic approaches. Because excessive hair growth in women may cause
      psychological and psychosocial problems, a holistic treatment approach, including
      support and emotional coping strategies, should be recommended. In this article,
      diagnostic procedures and treatment options for excessive hair growth in female
      patients are discussed.

PMID- 23159177
TI  - Drugs and hair loss.
AB  - Hair loss is a common complaint, both in men and women, and use of prescription
      medications is widespread. When there is a temporal association between the onset
      of hair loss and commencement of a medication, the medication is commonly thought
      to have caused the hair loss. However, hair loss and in particular telogen
      effluvium may occur in response to a number of triggers including fever,
      hemorrhage, severe illness, stress, and childbirth, and a thorough exclusion of
      these potential confounders is necessary before the hair loss can be blamed on
      the medication. Certain medications are known to cause hair loss by a variety of
      mechanisms including anagen arrest, telogen effluvium, or accentuation of
      androgenetic alopecia by androgens.

PMID- 23159178
TI  - Autoimmune disease and hair loss.
AB  - Once systemic disease is in remission, it is prudent to recognize the importance
      of alopecia in the patient's overall sense of well-being and quality-of-life
      clinical outcome. Scarring alopecia (scalp discoid lupus erythematosus) can be
      the presenting manifestation of lupus in more than half of affected individuals.
      Diffuse nonscarring alopecia in lupus is usually responsive to treatment of the
      systemic disease. Severe, often intractable burning pruritus of the scalp is a
      frequent complaint in dermatomyositis. Lichen planopilaris may mimic other
      autoimmune forms of scarring alopecia. Alopecia can also be caused by medications
      used to treat systemic autoimmune disease and fibromyalgia.

PMID- 23159179
TI  - Alopecia areata update.
AB  - Alopecia areata (AA) is a common nonscarring alopecia. It affects 1.7% of the
      population at some point in their lives. AA is an autoimmune condition
      characterized by dense peribulbar lymphocytic infiltrate. The exact cause and
      triggering factors are still unknown. The scalp is the most commonly affected
      area but any hair-bearing area can be involved. All available treatment options
      are neither curative nor preventive. This article will discuss updates in AA with
      focus on etiopathogenesis, clinical presentation, and treatment options and
      suggest treatment plans based on the age of the patient and extent of the
      disease.

PMID- 23159181
TI  - Hair: what is new in diagnosis and management? Female pattern hair loss update:
      diagnosis and treatment.
AB  - Female pattern hair loss (FPHL) is the most common cause of alopecia in women.
      FPHL is characterized histologically with increased numbers of miniaturized,
      velluslike hair follicles. The goal of treatment of FPHL is to arrest hair loss
      progression and stimulate hair regrowth. The treatments for FPHL can be divided
      into androgen-dependent and androgen-independent. There is an important adjuvant
      role for nutritional supplements, light therapy, and hair transplants. All
      treatments work best when initiated early. Combinations of treatments tend to be
      more efficacious.

PMID- 23159180
TI  - Genetic basis of alopecia areata: a roadmap for translational research.
AB  - Alopecia areata (AA) is a recurrent autoimmune type of hair loss that affects
      about 5.3 million people in the United States alone. Despite being the most
      prevalent autoimmune disease, the molecular and cellular mechanisms underlying
      this complex disease are still poorly understood, and rational treatments are
      lacking. Further efforts are necessary to clearly pinpoint the causes and
      molecular pathways leading to this disease and to find evidence-based treatments
      for AA. The authors focus on the central role of genetics for gaining insight
      into disease pathogenesis and setting the stage for the rational development of
      novel effective therapeutic approaches.

PMID- 23159182
TI  - Pattern hair loss in men: diagnosis and medical treatment.
AB  - Androgenetic alopecia is a common cause of hair loss in both men and women. The
      exact pathogenesis of androgenetic alopecia is not well understood. As the name
      implies, the role of androgens and genetic susceptibility predisposes to pattern
      hair loss due to gradual conversion of terminal hair into vellus hair. Male and
      female pattern hair loss are clinically distinct entities but histologically
      indistinguishable. The role of sex hormones in females is less understood. This
      article discusses current understanding of the etiopathogenesis of hair loss in
      men, diagnostic tests available, and its medical management.

PMID- 23159183
TI  - Hair transplantation update: procedural techniques, innovations, and
      applications.
AB  - The advances in hair transplantation, particularly the advent of follicular unit
      transplantation, have greatly elevated the outcome of this procedure. Various
      modifications to the basic technique as well as innovations focused on the
      different aspects of the hair transplantation procedure have further enhanced
      this type of hair restoration surgery. In addition, there is ongoing expansion of
      the indications and applications of this procedure beyond the usual male pattern
      hair loss.

PMID- 23159184
TI  - Primary cicatricial alopecias.
AB  - Primary cicatricial alopecias refer to a group of rare, idiopathic, inflammatory
      scalp disorders that result in permanent hair loss. Primary cicatricial alopecias
      comprise a diverse group of inflammatory diseases and can be classified via
      different approaches, such as clinical presentation, histopathologic findings, or
      both. Primary cicatricial alopecias are rare scalp disorders. Whiting found a
      prevalence of 7.3% in all patients who sought advice for hair and scalp problems
      at the Baylor Hair Research and Treatment Center in Dallas between 1989 and 1999.

PMID- 23159185
TI  - Nutrition and hair: deficiencies and supplements.
AB  - Hair follicle cells have a high turnover. A caloric deprivation or deficiency of
      several components, such as proteins, minerals, essential fatty acids, and
      vitamins, caused by inborn errors or reduced uptake, can lead to structural
      abnormalities, pigmentation changes, or hair loss, although exact data are often
      lacking. The diagnosis is established through a careful history, clinical
      examination of hair loss activity, and hair quality and confirmed through
      targeted laboratory tests. Examples of genetic hair disorders caused by reduced
      nutritional components are zinc deficiency in acrodermatitis enteropathica and
      copper deficiency in Menkes kinky hair syndrome.

PMID- 23159186
TI  - Shampoos, conditioners, and camouflage techniques.
AB  - This article examines hair care in persons with hair loss. The use of shampoos,
      conditioners, and hair styling products to camouflage hair loss is discussed.
      Because hair is nonliving, medical treatments are limited to only inducing change
      in the follicles within the scalp skin and do not improve the hair loss actually
      witnessed by the patient. There is therefore a need to accompany medical
      treatment of hair loss with cosmetic hair treatment to optimize patient
      satisfaction.

PMID- 23159187
TI  - Long-term removal of unwanted hair using light.
AB  - Laser (or light) hair removal, also referred to as photoepilation, is the most
      commonly used laser or light-based cosmetic medical procedure. The extended
      theory of selective photothermolysis is the basic principle for destruction of
      hair follicles using light. In this type of laser application the chromophore is
      follicular melanin. Several types of lasers and light sources have been effective
      for hair reduction, including the ruby, alexandrite, diode, and neodymium:yttrium
      aluminum-garnet lasers and broadband, intense pulsed light sources. This article
      provides a broad overview of how hair can be removed using light, with an
      emphasis on practical considerations.

PMID- 23159188
TI  - Utilizing electromagnetic radiation for hair growth: a critical review of
      phototrichogenesis.
AB  - Hair loss has a high prevalence in the general population and can have
      significant medical and psychological sequelae. Pattern hair loss and alopecia
      areata represent the major reasons patients present to dermatologists in relation
      to hair loss. Because conventional treatment options are generally incompletely
      effective, novel methods for hair grown induction are being developed. The role
      of using electromagnetic radiation, including low-level laser therapy for the
      management of hair loss through phototrichogenesis, is reviewed in this article.

PMID- 23159189
TI  - A spectrum of hair topics.

PMID- 23159190
TI  - Stratigraphic context and paleoenvironmental significance of minor taxa (Pisces,
      Reptilia, Aves, Rodentia) from the late Early Pleistocene paleoanthropological
      site of Buia (Eritrea).
AB  - The Buia Homo site, also known as Wadi Aalad, is an East African
      paleoanthropological site near the village of Buia that, due to its very rich
      yield from the late Early Pleistocene, has been intensively investigated since
      1994. In this paper, which reports on the finds of the 2010-2011 excavations, we
      include new fossil evidence on previously identified taxa (i.e., reptiles), as
      well as the very first description of the small mammal, fish and bird remains
      discovered. In particular, this study documents the discovery of the first
      African fossil of the genus Burhinus (Aves, Charadriiformes) and of the first
      rodent from the site. This latter is identified as a thryonomyid rodent (cane
      rat), a relatively common taxon in African paleoanthropological faunal
      assemblages. On the whole, the new occurrences documented within the Buia
      vertebrate assemblage confirm the occurrence of taxa characterized by strong
      water dependence. The paleoenvironmental characteristics of the fauna are
      confirmed as fully compatible with the evidence obtained through sedimentology
      and facies analysis, documenting the sedimentary evolution of fluvio-deltaic and
      lacustrine systems.

PMID- 23159191
TI  - Physical functioning is related to both an impaired physical ability and ADL
      disability: a ten year follow-up study in middle-aged and older persons.
AB  - OBJECTIVE: Identification of measures of physical function that mediate or link
      impaired physical ability with disability in activities of daily living (ADL) is
      necessary to facilitate the development of interventions to prevent or delay the
      onset of ADL disability. We examined whether measures of physical function at
      baseline are determinants of the Short Physical Performance Battery, as measure
      of physical ability, and disability, at ten years follow-up. STUDY DESIGN:
      Prospective cohort study in 625 middle-aged and older persons. MAIN OUTCOME
      MEASURES: Physical ability was measured by Guralniks Short Physical Performance
      Battery (impaired physical ability: score <6) and ADL ability by the KATZ
      questionnaire (ADL disability: score >= 1). Physical function was measured by
      lung function (in men only), handgrip strength, leg strength, and physical
      activity. The associations between physical function and the dichotomized
      impaired physical ability and disability-score were estimated using Poisson
      regression. RESULTS: Better lung function and higher leg strength were associated
      with a lower risk of having impaired physical ability, RR=0.98, 95% CI [0.96;
      0.99] per 10 L/min and RR=0.97, 95% CI [0.94; 0.99] per 10Nm, respectively.
      Higher handgrip strength, leg strength and level of physical activity were
      associated with a lower risk of having ADL disability, RR=0.72, 95% CI [0.57;
      0.92] per 10 kg, RR=0.95, 95% CI [0.92; 0.98] per 10Nm, RR=0.98, 95% CI [0.96;
      0.99] per point-score, respectively. Additional adjustment for baseline ADL
      disability did not materially changed the point-estimates (except for handgrip
      strength). CONCLUSION: Overall, leg extensor strength was associated with both an
      impaired physical ability and ADL disability. Other measures of physical
      functioning were either related to an impaired physical ability or ADL
      disability. ADL disability may be an intermediate factor for hand grip strength
      in the causal chain from impaired physical ability to ADL disability at follow
      up. The results of this study show that leg strength might be a relevant
      parameter to consider for future intervention studies.

PMID- 23159192
TI  - Gait characteristics and lower limb muscle strength in women with early and
      established knee osteoarthritis.
AB  - BACKGROUND: Based on novel classification criteria using magnetic resonance
      imaging, a subpopulation of "early knee osteoarthritis patients" was clearly
      defined recently. This study assessed whether these early osteoarthritis patients
      already exhibit gait adaptations (knee joint loading in particular) and changes
      in muscle strength compared to control subjects and established knee
      osteoarthritis patients. METHODS: Fourteen female patients with early knee joint
      degeneration, defined by magnetic resonance imaging (early osteoarthritis), 12
      female patients with established osteoarthritis and 14 female control subjects
      participated. Specific gait parameters and lower limb muscle strength were
      analyzed and compared between groups. Within the osteoarthritis groups,
      association between muscle strength and dynamic knee joint loading was also
      evaluated. FINDINGS: Early osteoarthritis patients presented no altered gait
      pattern, no significant increase in knee joint loading and no significant
      decrease in hamstring muscle strength compared to controls, while established
      osteoarthritis patients did. In contrast, early osteoarthritis patients
      experienced significant quadriceps weakness, comparable to established
      osteoarthritis patients. Within the osteoarthritis groups, muscle strength was
      not correlated with knee joint loading during gait. INTERPRETATION: The results
      suggest that gait changes reflect mechanical overload and are most likely the
      consequence of structural degeneration in knee osteoarthritis. Quadriceps
      weakness might however contribute to the onset and progression of the disease.
      This study supports the relevance of classification of early osteoarthritis
      patients and assists in identifying their functional characteristics. This helps
      to understand the trajectory of disease onset and progression and further develop
      more targeted strategies for prevention and treatment of knee osteoarthritis.

PMID- 23159193
TI  - How should we manage oral leukoplakia?
AB  - The aim of this article is to review the management of oral leukoplakia. The
      topics of interest are clinical diagnosis, methods of management and their
      outcome, factors associated with malignant transformation, prognosis, and
      clinical follow-up. Global prevalence is estimated to range from 0.5 to 3.4%. The
      point prevalence is estimated to be 2.6% (95% CI 1.72-2.74) with a reported rate
      of malignant transformation ranging from 0.13 to 17.5%. Incisional biopsy with
      scalpel and histopathological examination of the suspicious tissue is still the
      gold standard for diagnosis. A number of factors such as age, type of lesion,
      site and size, dysplasia, and DNA content have been associated with increased
      risk of malignant transformation, but no single reliable biomarker has been shown
      to be predictive. Various non-surgical and surgical treatments have been
      reported, but currently there is no consensus on the most appropriate one.
      Randomised controlled trials for non-surgical treatment show no evidence of
      effective prevention of malignant transformation and recurrence. Conventional
      surgery has its own limitations with respect to the size and site of the lesion
      but laser surgery has shown some encouraging results. There is no universal
      consensus on the duration or interval of follow-up of patients with the
      condition.

PMID- 23159194
TI  - Posterior auricular nerve found anterior to the cartilage of the external
      auditory meatus--a previously unreported variant.
AB  - We describe a previously unreported anatomical variant of the posterior auricular
      nerve found during parotidectomy, and discuss its clinical implications.

PMID- 23159195
TI  - Adverse childhood experiences and their impact on frequency, severity, and the
      individual function of nonsuicidal self-injury in youth.
AB  - This study aimed to investigate a specific relationship between nonsuicidal self
      injury (NSSI) and a variety of adverse childhood experiences (ACEs) over and
      above childhood abuse and their impact on frequency, severity, and functions of
      NSSI. A sample of 125 inpatients (aged 13 to 26) was consecutively recruited
      within a psychiatric university hospital. Frequency, methods and functions of
      NSSI were assessed by the Functional Assessment of Self-Mutilation (FASM), ACEs
      were assessed by the Childhood Experiences of Care and Abuse Questionnaire
      (CECA.Q). The 12 month prevalence of NSSI in this representative, clinical sample
      was 60.0%. Engagement in NSSI was significantly related to ACEs with highest
      associations for maternal antipathy and neglect. Whilst ACEs were not associated
      with frequency or severity of NSSI, some ACEs were significantly related to the
      automatic functions of NSSI (e.g., affect regulation, anti-dissociative function
      or self-punishment) as well as to a peer identification function. NSSI represents
      a frequent phenomenon among young clinical populations and seems to be
      specifically related to ACEs with maternal antipathy or neglect commonly featured
      over and above experiences of abuse. Since ACEs also influence the functions of
      NSSI such factors need to be examined as part of clinical care planning.

PMID- 23159196
TI  - The course of cognitive functioning over six months in individuals at clinical
      high risk for psychosis.
AB  - Cognitive impairment is common in psychosis and has recently been observed in
      individuals at clinical high risk (CHR) of developing psychosis. The purpose of
      this study was to characterize longitudinal change in cognition among CHR
      individuals, and compare cognition of CHR individuals who later convert to
      psychosis to that of CHR who do not convert. Participants were tested at baseline
      and followed-up after six months using a comprehensive cognitive test battery.
      Individuals who did not convert to psychosis either remained stable or
      significantly improved in their cognitive performance. At baseline participants
      who converted to psychosis compared to non-converters exhibited poorer
      performance in several cognitive tests, suggesting that some cognitive impairment
      is already present before conversion. Future longitudinal research should address
      if further decline takes place during the prodrome or after conversion to
      psychosis.

PMID- 23159197
TI  - Plasma low-density lipoprotein immobilized silica as stationary phase in nano
      liquid chromatography.
AB  - The feasibility to attach plasma low-density lipoprotein (LDL) particles
      covalently onto 5 MUm silica particles and use them as stationary phase in nano
      liquid chromatography (nano-LC) for interaction and oxidation studies was
      clarified. Before the immobilization, both epoxy silica and aldehyde-activated
      particles were synthesized, LDL was immobilized to the particles via its protein
      component and capillary columns were packed with LDL-modified silica materials.
      The performance of the capillary columns was tested with neutral steroids, and
      the column with LDL immobilized to aldehyde-activated silica was selected for
      further studies due to its stronger retention toward steroids. The retention
      factors of the steroids were used as indicators of the column stability, and the
      RSDs from 0.8 to 5.7% (n=12) for 168 successive runs within 14 days carried out
      in the same capillary column and from 0.8 to 3.6% (n=6) in three different
      capillaries demonstrated that the capillary column was stable and that the
      capillary column-to-capillary column reproducibility was good. The lifetime of
      LDL-modified silica stationary phase was around 14 days. The applicability of the
      column for the separation of steroids and beta-blockers was based mainly on the
      hydrophobic interactions with lipids of LDL in the stationary phase. The LDL
      immobilized silica column was successfully exploited also in the copper-mediated
      in situ oxidation of LDL. The results achieved demonstrated that nano-LC with
      plasma LDL immobilized silica phase can be exploited as nano-biomimicking tool
      for interaction studies and as a microreactor for oxidation studies with low
      consumption of reagents and human materials.

PMID- 23159198
TI  - Computational-aided design of molecularly imprinted polymer for selective
      extraction of methadone from plasma and saliva and determination by gas
      chromatography.
AB  - The main objective of this research was computational designing of an imprinted
      polymer for selective solid phase extraction (SPE) of methadone from plasma and
      saliva samples analyzed by gas chromatography-flam ionization detector (GC-FID).
      The density functional theory (DFT) at B3LYP/6-31G+ (d, p) level and Gaussian
      2003 package was used to calculate the interaction energy of template-monomers
      (DeltaE). The effect of polymerization solvent was also studied using polarizable
      continuum model (PCM). It was shown that, methacrylic acid (MAA) gave the largest
      DeltaE in acetonitrile as a polymerization solvent. To examine the validity of
      this approach, two MIP were synthesized for methadone as template molecule and
      methacrylic acid as functional monomer in acetonitrile (AN) and methanol (MeOH),
      respectively. The performance of each polymer was evaluated by using imprinting
      effect. As it is expected, the best results were obtained for the molecularly
      imprinted polymer (MIP) which was prepared in AN. For the optimized method, the
      linearity between responses (peak areas) and concentration of methadone in plasma
      and saliva samples were found over the range of 3.6-40,000 ng mL(-1) (R(2)=0.997)
      and 3.0-40,000 ng mL(-1) (R(2)=0.998), respectively. The limit of detection (LOD)
      and limit of quantification (LOQ) for methadone in plasma were calculated to be
      2.45 and 3.6 ng mL(-1), respectively. The LOD and LOQ for methadone in saliva
      were 2.14 and 3.0 ng mL(-1), respectively. The relative standard deviation (RSD;
      n=4) for plasma samples containing 10, 100, 500, 1000 ng mL(-1)of methadone were
      5.98, 5.78, 5.52, 4.78, 4.74, and the RSD (n=4) for saliva sample containing 5,
      20, 100, 1000 ng mL(-1) of methadone were 4.74, 5.1, 5.9, 5.6, respectively.

PMID- 23159199
TI  - The effect of co-occurring polychlorinated biphenyls on quantitation of toxaphene
      in fish tissue samples by gas chromatography negative ion mass spectrometry.
AB  - Determinative methods based on gas chromatography-negative chemical ionization
      mass spectrometry (GC-NCI/MS) provide improved sensitivity and specificity for
      toxaphene in environmental samples, but are subject to misidentification due to
      oxygen reaction in the presence of polychlorinated biphenyls (PCBs). The goal of
      this study was to quantify the impact of co-occurring PCBs in fish tissue samples
      when utilizing single quadrupole instruments to implement this method. Mixtures
      of PCB congeners and technical toxaphene, and extracts of fish tissue with
      varying concentrations of PCBs were analyzed for individual congener and total
      toxaphene concentrations by GC-NCI/MS. The contribution of co-injected PCB 204
      ranged from 23% to 88% of the total peak area for the Cl-9 toxaphene homolog
      quantitation ion, a contribution that increased as the ratio of technical
      toxaphene to PCB 204 decreased. PCB interferences in fish tissue extracts,
      including a standard reference material, were subtracted using a three-step
      procedure featuring spectral analysis of isotopic patterns for target peaks.
      Total toxaphene concentrations without PCB subtraction in three fish tissue
      samples with low, intermediate and high co-occurring PCBs were overestimated by
      33, 55 and 745%, respectively, underscoring the need for practical strategies to
      account for PCB interferences in GC-NCI/MS based protocols. In contrast, no
      appreciable interference or resulting positive bias in concentrations was
      observed for quantitation of eight common toxaphene residue congeners.

PMID- 23159200
TI  - Dioxins (polychlorinated dibenzo-p-dioxins and polychlorinated dibenzo-furans) in
      traditional clay products used during pregnancy.
AB  - Geophagy, the practice of consuming clay or soil, is encountered among pregnant
      women in Africa, Eastern Asia and Latin America, but also in Western societies.
      However, certain types of clay are known to contain high concentrations of
      polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs). The aim of this
      study was to determine the PCDD/F contents of orally consumed clays purchased
      from Dutch and African markets. Congener patterns were compared with those of
      pooled human milk samples collected in eight African countries, to investigate a
      possible relationship with clay consumption. From the Dutch market thirteen clay
      products were examined, seven of African and six of Suriname origin. From seven
      African countries, twenty clay products were collected. All 33 clay products were
      screened with a cell-based bioassay and those showing a high response were
      analyzed by GC/HRMS. High PCDD/F concentrations were measured in three clay
      products from the Dutch market, ranging from 66 to 103 pg TEQ g(-1), whereas clay
      products from African countries were from 24 to 75 pg TEQ g(-1). Patterns and
      relatively high concentrations of PCDD/Fs in human milk samples from the
      Democratic Republic of the Congo and Cote d'Ivoire suggest a relationship with
      the consumption of contaminated clay. Frequent use of PCDD/F contaminated clay
      products during pregnancy may result in increased exposure of the mother and
      subsequently the developing fetus and new-born child. The use of these
      contaminated clays during pregnancy should be carefully considered or even
      discouraged.

PMID- 23159201
TI  - [Maternal benefits and risks of trial of labor versus elective repeat caesarean
      delivery in women with a previous caesarean delivery].
AB  - OBJECTIVE: To assess maternal outcomes during trial of labor (TOL) and elective
      repeat caesarean delivery (ERCD) in women with a previous caesarean delivery.
      METHODS: French and English publications were searched using PubMed and Cochrane
      Library. RESULTS: Maternal mortality remains a very rare event regardless of the
      planned mode of delivery (EL2). It is potentially reduced after a TOL but the
      presence of biases in many studies does not allow any conclusion (EL3). Maternal
      morbidity is mainly due to the failure of the TOL and to the risk of unplanned
      caesarean delivery during labor (EL2). The risk of complete uterine rupture
      significantly increases with TOL versus ERCD but it remains low at about 0.2 to
      0.8% for women with one scar on the uterus (EL2). The occurrence of a post
      surgical wound, mostly from the bladder, is rare (less than 0.5%) regardless of
      the planned mode of delivery (EL2). Facing the risk of hemorrhage requiring
      hysterectomy or blood transfusion, data are heterogeneous because of the nature
      of the populations studied. These risks do not seem to vary with the mode of
      delivery (EL3). The risk of post-partum venous thrombo-embolic complications and
      infections (endometritis and maternal fever) appears to be similar in both TOL
      and ERCD (EL3). The risk of infection is primarily related to the additional
      presence of obesity (EL2). While maternal morbidity progressively increases with
      the number of iterative caesarean sections, maternal morbidity in TOL after a
      previous caesarean delivery decreases with the number of successful TOL (EL2).
      CONCLUSION: In patients with a previous caesarean delivery, the risks of maternal
      complications are rare and similar between TOL and ERCD. There is an increased
      risk of complete uterine rupture in case of TOL. Nevertheless TOL has a favorable
      benefit/risk balance in most cases and its success reduces the risk of short and
      long-term maternal complications (EL3).

PMID- 23159202
TI  - [Follow-up and counselling after pelvic inflammatory disease].
AB  - Pelvic inflammatory disease (PID) can be responsible for infertility and chronic
      pelvic pain. Treatment of acute PID is very important as it can reduce the risk
      of sequelae. However, follow-up, partner treatment and counselling are also
      useful to reduce the reinfection rate. Few weeks after PID, clinical evaluation
      as well as transvaginal and transabdominal sonography must be performed. The
      interest of systematic bacteriological tests is not proved. Hysterosalpingography
      and second-look laparoscopy should be considered only for women with infertility
      and severe infection. Use of condom is advisable in this population in order to
      prevent sexually transmitted diseases (STD) including HIV and to decrease rate of
      recurrence, associated to contraceptive pill, which is also a good option. In
      selected cases, intrauterine devices can be used in patients with history of PID
      if the infection is resolved and no significant risk factors for STD exist.
      Infertility and chronic pelvic pain are the most common sequelae in the
      population of young women with severe and recurrent infection. The risk of
      ectopic pregnancy is higher for these women and must be kept in mind. Counselling
      and risk-reduction interventions decreased significatively the rate of recurrence
      and sequelae in PID.

PMID- 23159203
TI  - Uric acid and high sensitive C-reactive protein are associated with subclinical
      thoracic aortic atherosclerosis.
AB  - BACKGROUND AND PURPOSE: The detection of atherosclerotic lesions in the aorta by
      transesophageal echocardiography (TEE) is a marker of diffuse atherosclerotic
      disease. Hyperuricemia is a well-recognized risk factor for cardiovascular
      diseases. However, no data are available concerning the relationship between
      serum uric acid (UA) and subclinical thoracic aortic atherosclerosis. We aimed to
      investigate the association between thoracic aortic atherosclerosis and serum UA
      level. METHODS: We studied 181 patients (mean age 46.3 +/- 8 years) who underwent
      TEE for various indications. Four different grades were determined according to
      intima-media thickness (IMT) of thoracic aorta. UA and other biochemical markers
      were measured with an automated chemistry analyzer. RESULTS: TEE evaluation
      characterized thoracic aortic intimal morphology as Grade 1 in 69 patients, Grade
      2 in 52 patients, Grade 3 in 31 patients, and Grade 4 in 29 patients. The highest
      UA level was observed in patients with Grade 4 IMT when compared with Grade 1 and
      2 IMT groups (p<0.001 and p=0.014, respectively). UA levels in patients with
      Grade 3 and Grade 2 IMT were also higher than patients with Grade 1 IMT group
      (p<0.001, for all). In multiple linear regression analysis, IMT was independently
      associated with UA level (beta=0.350, p<0.001), age (beta=0.219, p=0.001), total
      cholesterol (beta=-0.212, p=0.031), low-density lipoprotein cholesterol
      (beta=0.350, p=0.001), and high sensitivity C-reactive protein (hsCRP) levels
      (beta=0.148, p=0.014). CONCLUSION: Uric acid and hsCRP levels are independently
      and positively associated with subclinical thoracic atherosclerosis.

PMID- 23159204
TI  - Plasma homocysteine is associated with ischemic findings without organic stenosis
      in patients with slow coronary flow.
AB  - AIM: To investigate the plasma concentrations of homocysteine (Hcy) in slow
      coronary flow (SCF) patients before and at the end of the exercise test and
      compare with the values of healthy controls. METHODS: Study population consisted
      of 41 patients with SCF [68% men, aged 49 +/- 8 years], and 41 subjects with
      normal epicardial coronary arteries [56% men, aged 50 +/- 9 years]. Exercise test
      was performed in all study participants. Blood samples were drawn at rest and
      immediately at the end of exercise testing after 12h of overnight fasting.
      RESULTS: The baseline Hcy value of the SCF patients was higher than that of the
      control subjects (p<0.0001), and this difference continued after exercise test
      between the groups (p<0.0001). Median post-exercise increases in Hcy levels were
      higher in the SCF group than in the control group, without a significant
      difference (p=0.088). In the SCF group after exercise, Hcy levels in 17 patients
      with angina and 18 patients with ST depression were higher than those without
      angina and ST depression (p<0.0001 and p<0.0001, respectively). In addition, Hcy
      values in patients with both angina and ST depression were greater than those
      with either angina (p<0.05) or ST depression (p<0.05). CONCLUSION: The results of
      this study show that there is an important pathophysiologic link between the
      increased levels of plasma Hcy, the degree of ischemic findings, and the severity
      of slow flow in SCF patients.

PMID- 23159205
TI  - Role of central oxytocin in stress-induced cardioprotection in ischemic
      reperfused heart model.
AB  - BACKGROUND AND PURPOSE: There is growing evidence that stress contributes to
      cardiovascular disease and triggers the release of oxytocin. Moreover previous
      studies confirmed oxytocin mimics the protection associated with ischemic
      preconditioning. The present study was aimed to assess the possible
      cardioprotective effects of the centrally released oxytocin in response to stress
      and intracerebroventricular (i.c.v.) administration of exogenous oxytocin in
      ischemic-reperfused isolated rat heart. METHODS AND SUBJECTS: Rats were divided
      in two main groups and all of them were subjected to i.c.v. infusion of vehicle
      or drugs: unstressed rats [control: vehicle, oxytocin (OT; 100 ng/5 MUl),
      atosiban (ATO; 4.3 MUg/5 MUl) as oxytocin antagonist, ATO+OT] and stressed rats
      [St: stress, OT+St, ATO+St]. After anesthesia, hearts were isolated and subjected
      to 30 min regional ischemia and 60 min reperfusion (IR). Acute stress protocol
      included swimming for 10 min before anesthesia. Myocardial function, infarct
      size, coronary flow, ventricular arrhythmia, and biochemical parameters such as
      creatine kinase and lactate dehydrogenase were measured. Ischemia-induced
      ventricular arrhythmias were counted during the occlusion period. RESULTS: The
      plasma levels of oxytocin and corticosterone were significantly elevated by
      stress. Unexpectedly hearts of stressed rats showed a marked depression of IR
      injury compared to control group. I.c.v. infusion of oxytocin mimicked the
      cardioprotective effects of stress, yet did not elevate plasma oxytocin level.
      The protective effects of both stress and i.c.v. oxytocin were blocked by i.c.v.
      oxytocin antagonist. CONCLUSIONS: These findings suggest that i.c.v. infusion of
      exogenous oxytocin and centrally released endogenous oxytocin in response to
      stress could play a role in induction of a preconditioning effect in ischemic
      reperfused rat heart via brain receptors.

PMID- 23159206
TI  - Characteristics of patients and types of lesions in patients with drug-eluting or
      bare-metal stent implantation in small coronary arteries: from the FU-Registry.
AB  - Although the use of drug-eluting stents (DES) has reduced the rate of restenosis,
      some problems remain regarding the usefulness of DES in small coronary arteries
      in addition to late thrombosis and a longer duration of dual-antiplatelet
      therapy. We considered 335 patients with 698 lesions who underwent DES or bare
      metal stent (BMS) implantation, and randomly selected 172 DES and 124 BMS lesions
      that had undergone a complete data analysis and evaluation. Patients had a
      history of stable angina with at least 1 lesion with 50% diameter stenosis in a
      vessel and with a successfully minimum stent implantation (stent diameter=2.5mm).
      The baseline characteristics including the clinical presentation and
      cardiovascular risk factors were similar between the DES and BMS groups, except
      for the percentage of dyslipidemia (DL). Pre-procedure reference vessel diameter
      (RVD pre) in the DES group was significantly smaller than that in the BMS group
      (p<0.01), and stent length in the DES group was significantly longer (p<0.01).
      There was no significant difference in the cumulative incidence of major adverse
      cardiac events including the target lesion revascularization rate, whereas in
      stent restenosis (ISR) in the DES group was significantly lower than that in the
      BMS group. In a multivariate analysis of ISR, diabetes mellitus, prior
      percutaneous coronary intervention, and DES use in clinical background were
      identified as independent predictors of ISR. In addition, RVD pre, stent length,
      and DES use in angiographical background were also identified. In conclusion, DES
      use is an independent predictor of ISR, although the DES group included more
      severely diseased small coronary arteries.

PMID- 23159207
TI  - Impact of insulin resistance on 1-year clinical outcomes in non-diabetic patients
      undergoing percutaneous coronary intervention with drug-eluting stents.
AB  - BACKGROUND: Insulin resistance (IR) is known to be a risk factor for coronary
      artery disease (CAD). We aimed to evaluate the impact of IR on 1-year clinical
      outcomes in non-diabetic CAD patients who underwent percutaneous coronary
      intervention (PCI) with drug-eluting stents (DESs). METHODS AND RESULTS: A total
      of 229 consecutive non-diabetic CAD patients treated with DESs were enrolled.
      Study population was divided into IR group [homeostasis model assessment (HOMA)
      index >= 2.5, n=54] and non-IR group (HOMA index<2.5, n=175). Baseline clinical
      and procedural characteristics were similar between the groups except higher
      incidence of high-sensitivity C-reactive protein and lower incidence of
      multivessel disease as the target vessel in the non-IR group. There was a trend
      toward longer restenosis lesion length in the IR group at 6 months angiographic
      follow up but composite major clinical outcomes up to 1 year were similar between
      the two groups. CONCLUSIONS: Despite worse trend in angiographic outcomes in the
      IR group (HOMA index >= 2.5), it was not translated into worse 1-year major
      clinical outcomes following PCI with DESs as compared to the non-IR group.

PMID- 23159208
TI  - Controlling intracoronary CT number for coronary CT angiography.
AB  - BACKGROUND: Controlling intracoronary computed tomography (CT) number for
      coronary CT angiography (CCTA) has been difficult. OBJECTIVE: The study assessed
      whether intracoronary CT number of CCTA could be estimated. METHODS: One hundred
      twenty six patients were randomly assigned to either CCTA with 30 mL of contrast
      media (CM) following 5 mL of CM at timing bolus or CCTA with 50 mL of CM
      following 10 mL of CM at timing bolus. The relationships between intracoronary CT
      number and patients' characteristics and peak time and peak CT number at timing
      bolus in patients who showed valid time-density curve were analyzed in both
      groups. Then, the multiple regression equation best described was made. The
      prediction system was validated by 112 patients randomly targeted between 250 HU
      and 430 HU of CT number. RESULTS: In group 5/30, intracoronary CT number was
      positively correlated with peak CT number at timing bolus (correlation
      coefficient, 1.42, p<0.001), negatively correlated with body surface area (
      109.19, p<0.001) and peak time (-6.93, p<0.001). Whereas, intracoronary CT number
      was positively correlated with only peak CT number at timing bolus (1.33,
      p<0.001) in group 10/50. Then, CT number-controlling system using the simple
      equation best described CT number was established for CCTA following 5 mL of CM
      at timing bolus. Of 112 patients, there was good correlation between target CT
      number and measured CT number (r=0.85, p<0.0001) in 96 patients (85.7%), having
      valid time-density curve at timing bolus. CONCLUSIONS: Controlling CT number may
      be enabled by CT number-controlling system following 5 mL of CM at timing bolus.

PMID- 23159209
TI  - Reference interval of pregnancy-associated plasma protein-a in healthy men and
      non-pregnant women.
AB  - OBJECTIVE: The serum pregnancy-associated plasma protein-A (PAPP-A) concentration
      is a predictor of ischemic cardiac events and renal impairment. However, the
      reference interval of PAPP-A has not been determined. This study determined the
      reference interval of PAPP-A in men and non-pregnant women. METHODS: The study
      enrolled 126 apparently healthy individuals (52 males and 74 females). The mean
      age of the men and women was 34.7 (range 20-66) years and 34.6 (range 18-65)
      years, respectively. Serum PAPP-A concentrations were determined using an
      ultrasensitive enzyme-linked immunoassay kit. Reference intervals were calculated
      using the bootstrap method. RESULTS: The results for three subjects were
      outliers, so the reference interval of PAPP-A was calculated using the data for
      123 subjects. PAPP-A was undetectable in 26 subjects. The reference interval of
      PAPP-A for men and women (with the 90% confidence interval) was <22.9 ng/mL (19.7
      23.3) and <33.6 ng/mL (25.2-36.7), respectively. In male subjects, serum PAPP-A
      levels of smokers [3.10 (UD, 7.30)ng/mL] were significantly lower than that of
      non-smokers [11.00 (UD, 24.4)ng/mL] (p<0.001) and there was a positive
      correlation between serum PAPP-A levels and subjects' age (r=0.439; p<0.001).
      CONCLUSIONS: The reference interval of PAPP-A differed for men and non-pregnant
      women. In clinical practice, <22.9 ng/mL for men and <33.6 ng/mL for non-pregnant
      women may be used as reference intervals for PAPP-A.

PMID- 23159210
TI  - Tolvaptan reduces the risk of worsening renal function in patients with acute
      decompensated heart failure in high-risk population.
AB  - BACKGROUND: Although tolvaptan is a recently approved drug for heart failure and
      causes aquaresis without affecting renal function, its clinical efficacy for
      patients with acute decompensated heart failure (ADHF) is yet to be elucidated.
      METHODS AND RESULTS: We conducted a prospective observational study in patients
      with ADHF and high risk for worsening renal function (WRF). Risk stratification
      for WRF was done by scoring system. Of 174 patients, 114 patients were included
      as high-risk population for WRF. Incidence of WRF, urine output within 24h and 48
      h, and changes in brain natriuretic peptide (BNP) were recorded in 44 patients
      treated with tolvaptan plus conventional therapy, and 70 patients with only
      conventional therapy. Urine output at 24h and 48 h after admission were both
      significantly higher in the tolvaptan group (p=0.001 and <0.001, respectively),
      and changes in BNP were not significantly different (p=0.351). However, the
      incidence of WRF was significantly lower in the tolvaptan group compared to the
      conventional group (22.7% vs 41.4%, p=0.045). Logistic regression analysis showed
      that treatment with tolvaptan was an independent factor for reducing WRF (hazard
      ratio 0.28, 95% confidence interval; 0.10-0.84; p=0.023). CONCLUSION: In patients
      with ADHF with high risk of WRF, treatment with tolvaptan could prevent WRF
      compared to conventional therapy.

PMID- 23159211
TI  - Prediction of atrial fibrillation after ischemic stroke using P-wave signal
      averaged electrocardiography.
AB  - BACKGROUND: Atrial fibrillation (AF) is highly prevalent in patients with
      ischemic stroke, but the diagnosis is often difficult. METHODS: This study
      consisted of 68 stroke patients in sinus rhythm without history of AF. All
      patients underwent P-wave signal-averaged electrocardiography (P-SAECG),
      echocardiography, 24-h Holter monitoring, and measurement of plasma B-type
      natriuretic peptide (BNP) concentrations at admission. RESULTS: An abnormal P
      SAECG was found in 34 of 68 stroke patients. In the follow-up period of 11 +/- 4
      months, AF developed in 17 patients (AF group). The remaining 51 patients were
      classified as the non-AF group. The prevalence of atrial late potentials (ALP) on
      P-SAECG, and the number of premature atrial contractions (PACs) were
      significantly higher in the AF group than those in the non-AF group (88.2% vs
      37.3%; p<0.001, 149 +/- 120 vs 79 +/- 69; p=0.030, respectively). However, there
      were no significant differences in age, left atrial dimension, or BNP
      concentrations between both groups. Cox proportional hazards analysis revealed
      that the presence of ALP (risk ratio 11.15; p=0.002) and frequent PACs (more than
      100/24h) (risk ratio 4.53; p=0.007) had significant correlation to the occurrence
      of AF. CONCLUSIONS: ALP may be a novel predictor of AF in stroke patients. P
      SAECG should be considered in stroke of undetermined etiology.

PMID- 23159212
TI  - Neonatal short bowel syndrome as a model of intestinal failure: physiological
      background for enteral feeding.
AB  - Intestinal failure (IF) is a well identified clinical condition, which is
      characterised by the reduction of functional gut capacity below the minimum
      needed for adequate digestion and absorption of nutrients for normal growth in
      children. Short bowel syndrome (SBS) is the leading cause of IF in neonates,
      infants and young children usually as a result of extensive intestinal resection
      during the neonatal period. Simultaneously maintaining optimal nutritional status
      and achieving intestinal adaptation is a clinical challenge in short bowel
      patients. Both growth and development of the child as well as gut adaptation
      should be considered synergistically as primary outcome parameters. Enteral
      nutrition (EN) can be introduced orally and/or by tube feeding (TF). Several
      controversies over nutritional treatment of children with SBS related intestinal
      failure remain. As reported from different centres around the world, most
      practices are more "experienced based" rather than "evidence based". This is
      partly due to the small number of patients with this condition. This review
      (based on a consensus) discusses the physiological principles and nutritional
      management, including the type of diet and route of delivery. Perspectives in
      optimizing intestinal adaptation and reducing the consequences of small
      intestinal bacterial overgrowth are also discussed.

PMID- 23159213
TI  - Breast conserving surgery using the round block technique combined with partial
      reconstruction using the latissimus dorsi flap.
AB  - The round block technique (RBT) is one of the frequently used volume displacement
      procedures in oncoplastic breast surgery. We report a useful technique which
      combines RBT with immediate partial breast reconstruction using the latissimus
      dorsi flap (LD flap) for breast-conserving surgery (BCS). A wide oval periareolar
      wound allows both resection of a large amount of a breast tissue and
      reconstructive procedures using the LD flap, which ultimately results in a
      minimal periareolar scar and a good cosmetic result. This combined technique may
      provide BCS with increasing indications and better cosmesis.

PMID- 23159214
TI  - Influence of gender on ischemic times and outcomes after ST-elevation myocardial
      infarction.
AB  - Previous studies investigating the influence of gender on ST-segment elevation
      myocardial infarction have reported conflicting results. The aim of this study
      was to assess the influence of gender on ischemic times and outcomes after ST
      segment elevation myocardial infarction in patients treated with primary
      percutaneous coronary intervention in modern practice. The present multicenter
      registry included consecutive patients with ST-segment elevation myocardial
      infarctions treated with primary percutaneous coronary intervention at 3
      hospitals. Adjusted mortality rates were calculated using Cox proportional
      hazards analyses. In total, 3,483 patients were included, of whom 868 were women
      (25%). Women were older, had a higher risk factor burden, and more frequently had
      histories of malignancy. Men more often had cardiac histories and peripheral
      vascular disease. Ischemic times were longer in women (median 192 minutes
      [interquartile range 141 to 286] vs 175 minutes [interquartile range 128 to 279]
      in men, p = 0.002). However, multivariate linear regression showed that this was
      due to age and co-morbidity. All-cause mortality was higher at 7 days (6.0% in
      women vs 3.0% in men, p <0.001) and at 1 year (9.9% in women vs 6.6% in men, p =
      0.001). After adjustment, female gender predicted 7 day all-cause mortality
      (hazard ratio 1.61, 95% confidence interval 1.06 to 2.46) and cardiac mortality
      (hazard ratio 1.58, 95% confidence interval 1.03 to 2.42) but not 1-year
      mortality. Moreover, gender was an independent effect modifier for cardiogenic
      shock, leading to substantially worse outcomes in women. In conclusion, ischemic
      times remain longer in women because of age and co-morbidity. Female gender
      independently predicted early all-cause and cardiac mortality after primary
      percutaneous coronary intervention, and a strong interaction between gender and
      cardiogenic shock was observed.

PMID- 23159215
TI  - miR-21 regulates skin wound healing by targeting multiple aspects of the healing
      process.
AB  - With the clarification of the important roles of microRNAs (miRNAs) in diverse
      physiologic and pathologic processes, the effects of miRNAs in wound healing have
      attracted more attention recently. However, the global pattern of miRNA
      expression in wound tissue is still unknown. In the present study, we depicted
      the miRNA profile and identified at least 54 miRNAs, including miR-21, changed
      for more than twofold at the stage of granulation formation during wound healing.
      These miRNAs were closely related to the major events of wound healing, including
      cell migration and proliferation, angiogenesis, and matrix remolding.
      Furthermore, we found that miR-21 was up-regulated after skin injury, mainly in
      activated and migrating epithelial cells of epidermis and mesenchymal cells of
      dermis. Locally antagonizing miR-21 by directly injecting antagomir to wound edge
      caused significant delay of wound closure with impaired collagen deposition.
      Unexpectedly, we found wounds treated with miR-21 antagomir had an obvious defect
      in wound contraction at an early stage of wound healing. The significant role of
      miR-21 in wound contraction was further confirmed by in vivo gain-of-function and
      in vitro loss-of-function experiments. In conclusion, the present study has for
      the first time depicted miRNA profiling of wound healing and demonstrated the
      involvement of miR-21 in regulating the wound contraction and collagen
      deposition. These results suggest that miR-21 may be a new medical target in skin
      wound manipulation.

PMID- 23159216
TI  - Myocyte shape regulates lateral registry of sarcomeres and contractility.
AB  - The heart actively remodels architecture in response to various physiological and
      pathological conditions. Gross structural change of the heart chambers is
      directly reflected at the cellular level by altering the morphological
      characteristics of individual cardiomyocytes. However, an understanding of the
      relationship between cardiomyocyte shape and the contractile function remains
      unclear. By using in vitro assays to analyze systolic stress of cardiomyocytes
      with controlled shape, we demonstrated that the characteristic morphological
      features of cardiomyocytes observed in a variety of pathophysiological conditions
      are correlated with mechanical performance. We found that cardiomyocyte
      contractility is optimized at the cell length/width ratio observed in normal
      hearts, and decreases in cardiomyocytes with morphological characteristics
      resembling those isolated from failing hearts. Quantitative analysis of
      sarcomeric architecture revealed that the change of contractility may arise from
      alteration of myofibrillar structure. Measurements of intracellular calcium in
      myocytes revealed unique characteristics of calcium metabolism as a function of
      myocyte shape. Our data suggest that cell shape is critical in determining
      contractile performance of single cardiomyocytes by regulating the intracellular
      structure and calcium handling ability.

PMID- 23159217
TI  - Targeting tumor neovasculature in non-small-cell lung cancer.
AB  - Recent insight into the molecular biology of cancer and mechanisms of
      tumorigenesis, has allowed for the identification of several potential molecular
      targets and the development of novel "targeted therapies". One of the most active
      research fields in NSCLC is the discovery of therapies that target angiogenesis.
      The vascular endothelial growth factor (VEGF) pathway represents a crucial
      component of the tumor angiogenesis process. Two different strategies have been
      developed in clinical practice in order to restrict tumor vasculature
      development; either the use of monoclonal antibodies against VEGF or small
      molecule tyrosine kinase inhibitors to target the tyrosine kinase domain of VEGF
      receptor. Among these agents that have been tested bevacizumab, a monoclonal
      antibody against VEGF, has been approved for the treatment of metastatic NSCLC in
      combination with chemotherapy, while several other agents are under phase III
      investigation. Moreover, several issues such as predictive biomarkers of response
      to antiangiogenic therapy and mechanisms of resistance to these agents remain to
      be elucidated. The purpose of this paper is to present the current status of
      antiangiogenic therapies in the treatment of NSCLC and to discuss these issues.

PMID- 23159218
TI  - Emerging concepts in the management and treatment of osteonecrosis of the jaw.
AB  - Since the first description of bone necrosis in patients receiving bisphosphonate
      therapy in 2004, there have been multiple retrospective, prospective, and case
      control studies that have served to characterize the diagnosis, associated risk
      factors, and treatment of this new complication. Bisphosphonate-related
      osteonecrosis of the jaw is at present associated with several risk factors that
      are identified across several disciplines in medicine and dentistry. With this
      level of broad-based recognition, new clinical and basic science research
      initiatives have begun and are likely to elucidate the etiopathogenesis of this
      disease process, significantly improving the level of disease management and
      prevention.

PMID- 23159219
TI  - The diagnosis and management of parotid disease.
AB  - A specific and regimented approach to the diagnosis and management of patients
      with disease of the parotid gland is necessary for correct diagnosis and
      management. Patient morbidity or mortality may result if there is a delay in the
      diagnosis of a malignant parotid tumor. This article reviews the diagnosis and
      management of parotid disease, with a particular concentration on neoplastic
      processes. An overview of the superficial parotid mass is emphasized because most
      neoplastic processes occupy the superficial lobe of the parotid gland.

PMID- 23159220
TI  - Identity crisis: it's not just Foxp3 anymore.
AB  - What does it take to make a regulatory T (Treg) cell? In this issue of Immunity,
      Ohkura et al. show that Treg-cell-specific CpG hypomethylation and Foxp3
      expression are independent events required for Treg cell development, stability,
      and full suppressive activity.

PMID- 23159221
TI  - Tales of the unexpected: Tcf1 functions as a tumor suppressor for leukemias.
AB  - The Wnt-responsive transcription factors Tcf1 and Lef1 are well-known for their
      roles in lymphocyte development. In this issue of Immunity, Yu et al. (2012)
      report that Tcf1-deficient mice develop aggressive T cell lymphomas that are
      characterized by high Lef1 expression.

PMID- 23159222
TI  - Retroviral danger from within: TLR7 is in control.
AB  - In this issue of Immunity, Yu et al. (2012) outline a fascinating model in which
      TLR7-mediated antibody production acts as a dominant immunosurveillance mechanism
      against endogenous retroviruses (ERVs), with additional support of TLR3 and TLR9
      that function to prevent ERV-mediated malignancy.

PMID- 23159223
TI  - Langerhans cells come in waves.
AB  - It is unclear how the Langerhans cell (LC) network is maintained in adult
      epidermis. In this issue of Immunity, Sere et al. (2012) show that LCs are
      replenished in two waves. Monocyte-derived, short-lived LCs come first. A second
      wave follows, and these LCs of nonmonocytic origin are long-lived.

PMID- 23159224
TI  - CEACAM1-S: the virtues of alternative splicing in gut immunity.
AB  - Immunoglobulin A (IgA) is the main intestinal antibody. In this issue of
      Immunity, Chen et al. (2012) show that intestinal T cells enhance protective IgA
      responses by expressing a short isoform of the CEACAM1 protein.

PMID- 23159227
TI  - Interferon-gamma excess leads to pathogenic accumulation of follicular helper T
      cells and germinal centers.
AB  - Overactivity of the germinal center (GC) pathway resulting from accumulation of
      follicular helper T (Tfh) cells causes autoimmunity, underscoring the need to
      understand the factors that control Tfh cell homeostasis. Here we have identifed
      posttranscriptional repression of interferon-gamma (Ifng) mRNA as a mechanism to
      limit Tfh cell formation. By using the sanroque lupus model, we have shown that
      decreased Ifng mRNA decay caused excessive IFN-gamma signaling in T cells and led
      to accumulation of Tfh cells, spontaneous GC, autoantibody formation, and
      nephritis. Unlike ICOS and T-bet deficiency that failed to rescue several
      autoimmune manifestations, interferon-gamma receptor (IFN-gammaR) deficiency
      prevented lupus development. IFN-gamma blockade reduced Tfh cells and
      autoantibodies, demonstrating that IFN-gamma overproduction was required to
      sustain lupus-associated pathology. Increased IFN-gammaR signaling caused Bcl-6
      overexpression in Tfh cells and their precursors. This link between IFN-gamma and
      aberrant Tfh cell formation provides a rationale for IFN-gamma blockade in lupus
      patients with an overactive Tfh cell-associated pathway.

PMID- 23159226
TI  - beta-Selection-induced proliferation is required for alphabeta T cell
      differentiation.
AB  - Proliferation and differentiation are tightly coordinated to produce an
      appropriate number of differentiated cells and often exhibit an antagonistic
      relationship. Developing T cells, which arise in the thymus from a minute number
      of bone-marrow-derived progenitors, undergo a major expansion upon pre-T cell
      receptor (TCR) expression. The burst of proliferation coincides with
      differentiation toward the alphabeta T cell lineage-but the two processes were
      previously thought to be independent from one another, although both were driven
      by signaling from pre-TCR and Notch receptors. Here we report that proliferation
      at this step was not only absolutely required for differentiation but also that
      its ectopic activation was sufficient to substantially rescue differentiation in
      the absence of Notch signaling. Consistently, pharmacological inhibition of the
      cell cycle machinery also blocked differentiation in vivo. Thus the proliferation
      step is strictly required prior to differentiation of immature thymocytes.

PMID- 23159228
TI  - Two distinct types of Langerhans cells populate the skin during steady state and
      inflammation.
AB  - Langerhans cells (LCs), the dendritic cells (DCs) in skin epidermis, possess an
      exceptional life cycle and developmental origin. Here we identified two types of
      LCs, short-term and long-term LCs, which transiently or stably reconstitute the
      LC compartment, respectively. Short-term LCs developed from Gr-1(hi) monocytes
      under inflammatory conditions and occurred independently of the transcription
      factor Id2. Long-term LCs arose from bone marrow in steady state and were
      critically dependent on Id2. Surface marker and gene expression analysis
      positioned short-term LCs close to Gr-1(hi) monocytes, which is indicative of
      their monocytic origin. We also show that LC reconstitution after UV light
      exposure occurs in two waves: an initial fast and transient wave of Gr-1(hi)
      monocyte-derived short-term LCs is followed by a second wave of steady-state
      precursor-derived long-term LCs. Our data demonstrate the presence of two types
      of LCs that develop through different pathways in inflammation and steady state.

PMID- 23159229
TI  - The influence of VKORC1 and CYP2C9 gene sequence variants on the stability of
      maintenance phase warfarin treatment.
AB  - INTRODUCTION: A substantial part of the inter-individual variation in vitamin K
      antagonist dose can be explained by certain sequence variants in the genes CYP2C9
      (NG_008385.1:g.8633C>T or *1/*2, NG_008385.1:g.47639A>C or *1/*3) and VKORC1
      (NG_011564.1:g.6399C>T). Patients possessing these variant alleles require lower
      doses and have increased risk of overanticoagulation. METHODS: We investigated
      the influence of the above sequence variants on stability of maintenance phase
      warfarin therapy in a prospective study of 300 consecutive patients followed for
      one year at an anticoagulant clinic. RESULTS: Patients having one VKORC1 variant
      allele (n=144) had a time in therapeutic range of INR (TTR) of 71.4%,
      significantly lower (p=0.02) than the 76.7% TTR of patients with none (n=96) or
      two (n=46) variant alleles. Patients carrying the CYP2C9 *3 allele (n=40) trended
      towards lower TTR than patients without this variant allele (69.8% vs. 74.7%,
      p=0.09). Six patients possessed two variant alleles of CYP2C9 (*2/*3 or *3/*3)
      and had significantly lower TTR (60.5% vs. 74.3%, p=0.012) and higher risk of an
      INR>4.5 (67% vs. 23%, p=0.03) compared with the remaining patients. CONCLUSIONS:
      We observed modest effects of common gene sequence variants in CYP2C9 and VKORC1
      on stability of maintenance phase warfarin therapy. Patients attending an
      anticoagulant clinic using computer-assisted dosage were safely monitored
      regardless of these sequence variants, but for the small subgroup of patients
      with the CYP2C9 genotype *2/*3 or *3/*3, treatment stability was reduced.

PMID- 23159225
TI  - Innate immune function by Toll-like receptors: distinct responses in newborns and
      the elderly.
AB  - Given the "inborn" nature of the innate immune system, it is surprising to find
      that innate immune function does in fact change with age. Similar patterns of
      distinct Toll-like-receptor-mediated immune responses come to light when one
      contrasts innate immune development at the beginning of life with that toward the
      end of life. Importantly, these developmental patterns of innate cytokine
      responses correlate with clinical patterns of susceptibility to disease: A
      heightened risk of suffering from excessive inflammation is often detected in
      prematurely born infants, disappears over the first few months of life, and
      reappears toward the end of life. In addition, risk periods for particular
      infections in early life reemerge in older adults. The near-mirror-image patterns
      that emerge in contrasts of early versus late innate immune ontogeny emphasize
      changes in host-environment interactions as the underlying molecular and
      teleologic drivers.

PMID- 23159230
TI  - Risk of myocardial infarction in patients with rhinosinusitis.
AB  - Research has indicated that inflammation promote all phases of atherosclerosis.
      The current study tested the hypothesis that rhinosinusitis is a risk marker for
      myocardial infarction (MI). Data on the general population were obtained from the
      Taiwan Longitudinal Health Insurance Database 2005 (LHID2005). The study cohort
      comprised patients who had received a recorded diagnosis of rhinosinusitis (N =
      52,930) between January 1, 2004 and December 31, 2004. The comparison group
      consisted of patients who had not received a rhinosinusitis diagnosis, and who
      were matched for age and sex with the study group at a ratio of 4 controls to 1
      study patient (1:4) (N = 211,720). Each patient's condition was followed using
      database entries until the end of 2006. Cox proportional hazard regressions were
      used to evaluate the 3-year MI-free survival rates, after adjusting for known
      confounding factors. We found that patients with rhinosinusitis were more likely
      than the control group to have MI, after adjusting for potential confounders
      [adjusted hazard ratio (HR), 1.84; 95% confidence interval (CI), 1.44 ~ 2.40]. Of
      the total 264 650 patients, 290 experienced MI during the 3-year follow-up
      period, including 8 acute sinusitis patients, 77 chronic sinusitis patients, and
      205 control patients. The incidence rate of MI was 6.19 (95% CI 5.01-7.65) per
      10,000 person-years for rhinosinusitis patients, compared to 3.51 (95% CI, 3.06
      4.02) for the control patients. From this study, rhinosinusitis may be associated
      with MI. Further research in this important area of public health is warranted.

PMID- 23159231
TI  - Two apolipoprotein E mimetic peptides with similar cholesterol reducing
      properties exhibit differential atheroprotective effects in LDL-R null mice.
AB  - OBJECTIVE: We investigated two apoE mimetic peptides with similar long-term
      plasma cholesterol reducing abilities for their effects on atherosclerotic
      lesions in Western diet-fed female LDL-receptor (LDL-R) null mice. METHODS AND
      RESULTS: Single doses of peptides Ac-hE18A-NH(2) and mR18L were administered
      retro-orbitally to LDL-R null mice on Western diet and plasma cholesterol was
      measured at 10 min, 4 h, and 24 h post administration. Peptide mR18L and not Ac
      hE18A-NH(2) reduced plasma cholesterol levels significantly at 4 h post
      administration. However, multiple administrations (100 MUg/mouse twice weekly for
      8 weeks) resulted in a similar reduction in plasma cholesterol. Only the plasma
      from the Ac-hE18A-NH(2) group had significantly reduced reactive oxygen species
      levels at the end of the treatment protocol. Both mR18L and Ac-hE18A-NH(2) showed
      reduced atherosclerotic lesion areas. However, peptide Ac-hE18A-NH(2) was
      significantly more effective in inhibiting atherosclerosis. Both peptides reduced
      total plaque macrophage load compared to the saline treated animals, with peptide
      Ac-hE18A-NH(2) having a greater reduction. Incubation of HepG2 cells and THP-1
      monocyte-derived macrophages with both peptides in the presence of oxidized
      phospholipid showed that Ac-hE18A-NH(2) promotes the secretion of apoE from the
      cells whereas mR18L does not. CONCLUSIONS: Despite similar reductions in plasma
      cholesterol levels, Ac-hE18A-NH(2) was more effective in inhibiting lesions than
      mR18L, possibly due to its ability to promote the secretion of apoE from
      hepatocytes and macrophages.

PMID- 23159232
TI  - Hemoglobin stability in patients with anemia, CKD, and type 2 diabetes: an
      analysis of the TREAT (Trial to Reduce Cardiovascular Events With Aranesp
      Therapy) placebo arm.
AB  - BACKGROUND: Sparse data are available about the natural history of hemoglobin
      (Hb) level trends in contemporary patients with anemia, chronic kidney disease
      (CKD), and type 2 diabetes mellitus. We intended to describe Hb level trends over
      time with no or minimal administration of erythropoiesis-stimulating agents.
      STUDY DESIGN: Prospective clinical trial cohort. SETTING & PARTICIPANTS: 2,019
      individuals with type 2 diabetes, moderate anemia, and CKD from the placebo arm
      of the Trial to Reduce Cardiovascular Events With Aranesp Therapy (TREAT)
      followed up for 2.3 years with an average of 32 monthly Hb level determinations
      per patient. Darbepoetin alfa was administered only if Hb level decreased to <9
      g/dL. OUTCOMES & MEASUREMENTS: Number of protocol-directed doses of darbepoetin
      alfa received due to an Hb level decrease to <9 g/dL. RESULTS: 1,106 (55%)
      placebo patients consistently maintained an Hb level >=9 g/dL and received no
      protocol-directed darbepoetin alfa. The other patients received 1 (16%), 2-4
      (16%), or 5 or more (13%) doses of darbepoetin alfa. Those who received no
      darbepoetin alfa doses had higher baseline Hb levels, higher estimated glomerular
      filtration rates (eGFRs), less proteinuria, and lower ferritin and transferrin
      saturation values. On average, Hb levels were stable or increased in all groups.
      Compared with individuals who received no darbepoetin alfa, those who received 5
      or more doses were more likely to receive intravenous iron therapy and blood
      transfusions and progress to renal replacement therapy, but were not at higher
      risk of death. The strongest predictors of requiring 5 or more doses of
      darbepoetin alfa were lower baseline Hb level, lower eGFR, and higher proteinuria
      level. LIMITATIONS: Post hoc analysis of a clinical trial of a specific
      population with diabetes, anemia, and non-dialysis-dependent CKD. CONCLUSIONS: In
      the TREAT placebo arm, Hb levels were stable with no or minimal protocol-directed
      darbepoetin alfa during 2.3 years of follow-up. Most patients with moderate
      anemia, non-dialysis-dependent CKD, and type 2 diabetes are able to maintain a
      stable Hb level without implementing long-term erythropoiesis-stimulating agent
      therapy.

PMID- 23159233
TI  - Influence of kidney function on risk of hemorrhage among patients taking
      warfarin: a cohort study.

PMID- 23159234
TI  - Hemodialysis access usage patterns in the incident dialysis year and associated
      catheter-related complications.
AB  - BACKGROUND: Hemodialysis (HD) access is considered a critical and actionable
      determinant of morbidity, with a growing literature suggesting that initial HD
      access type is an important marker of long-term outcomes. Accordingly, we
      examined HD access during the incident dialysis period, focusing on infection
      risk and successful fistula creation during the first dialysis year. STUDY
      DESIGN: Longitudinal cohort. SETTING & PARTICIPANTS: All US adults admitted to
      Fresenius Medical Care North America facilities within 15 days of first
      maintenance dialysis session between January 1 and December 31, 2007. PREDICTOR:
      Vascular access type at HD therapy initiation. OUTCOMES: Vascular access type at
      90 days and at the end of the first year on HD therapy, bloodstream infection
      within the first year by access type, and catheter complication rate. RESULTS: Of
      25,003 incident dialysis patients studied, 19,622 (78.5%) initiated dialysis with
      a catheter; 4,151 (16.6%), with a fistula; and 1,230 (4.9%), with a graft. At 90
      days, 14,105 (69.7%) had a catheter, 4,432 (21.9%) had a fistula, and 1,705
      (8.4%) had a graft. Functioning fistulas and grafts at dialysis therapy
      initiation had first-year failure rates of 10% and 15%, respectively. Grafts were
      seldom replaced by fistulas (3%), whereas 7,064 (47.6%) of all patients who
      initiated with a catheter alone still had only a catheter at 1 year. Overall,
      3,327 (13.3%) patients had at least one positive blood culture during follow-up,
      with the risk being similar between the fistula and graft groups, but
      approximately 3-fold higher in patients with a catheter (P<0.001 for either
      comparison). Nearly 1 in 3 catheters (32.5%) will require tissue plasminogen
      activator use by a median of 41 days, with 59% requiring more than one tissue
      plasminogen activator administration. LIMITATIONS: Potential underestimation of
      bacteremia because follow-up blood culture results did not include samples sent
      to local laboratories. CONCLUSIONS: In a large and representative population of
      incident US dialysis patients, catheter use remains very high during the first
      year of HD care and is associated with high mechanical complication and
      bloodstream infection rates.

PMID- 23159235
TI  - A conceptual model of psychosocial risk and protective factors for excessive
      gestational weight gain.
AB  - OBJECTIVE: nearly half of all women exceed the guideline recommended pregnancy
      weight gain for their Body Mass Index (BMI) category. Excessive gestational
      weight gain (GWG) is correlated positively with postpartum weight retention and
      is a predictor of long-term, higher BMI in mothers and their children.
      Psychosocial factors are generally not targeted in GWG behaviour change
      interventions, however, multifactorial, conceptual models that include these
      factors, may be useful in determining the pathways that contribute to excessive
      GWG. We propose a conceptual model, underpinned by health behaviour change
      theory, which outlines the psychosocial determinants of GWG, including the role
      of motivation and self-efficacy towards healthy behaviours. This model is based
      on a review of the existing literature in this area. ASSESSMENT AND CONCLUSION:
      there is increasing evidence to show that psychosocial factors, such as increased
      depressive symptoms, anxiety, lower self-esteem and body image dissatisfaction,
      are associated with excessive GWG. What is less known is how these factors might
      lead to excessive GWG. Our conceptual model proposes a pathway of factors that
      affect GWG, and may be useful for understanding the mechanisms by which
      interventions impact on weight management during pregnancy. This involves
      tracking the relationships among maternal psychosocial factors, including body
      image concerns, motivation to adopt healthy lifestyle behaviours, confidence in
      adopting healthy lifestyle behaviours for the purposes of weight management, and
      actual behaviour changes. IMPLICATIONS FOR PRACTICE: health-care providers may
      improve weight gain outcomes in pregnancy if they assess and address psychosocial
      factors in pregnancy.

PMID- 23159236
TI  - Development of a cytometric bead array screening tool for the simultaneous
      detection of pro-inflammatory cytokines in porcine plasma.
AB  - Lipopolysaccharide (LPS) has been widely used as a model of immune challenge in
      pigs as it induces the immediate synthesis of pro-inflammatory cytokines such as
      tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta) and IL-6,
      which trigger the production of the acute phase proteins (APPs) C-reactive
      protein (CRP), haptoglobin (Hp) and pig-Major Acute Phase Protein (pig-MAP). To
      measure secreted proteins in porcine plasma, specific and sensitive Enzyme-Linked
      Immuno Sorbent Assays (ELISAs) are well-suited to perform single parameter
      analysis, yet this approach is time-consuming and expensive for multi-parameter
      analyses. During the last decade, multiplex bead-based flow cytometry has been
      increasingly applied as it offers the opportunity to estimate protein ratios in a
      small sample volume. Cytometric bead array (CBA) is a flow cytometric application
      using a diversity of beads with unique fluorescence intensities, covalently
      coupled to a capture antibody for each protein of interest. Detection antibodies,
      either directly or indirectly conjugated to a fluorochrome, are added to
      accomplish the desired sandwich format. The aim of the present study was to
      develop a CBA 3-plex assay for the major pro-inflammatory cytokines TNF-alpha, IL
      1beta and IL-6, and an additional CBA 2-plex assay for the major APPs, CRP and
      pig-MAP, in porcine plasma. Results were compared to commercial ELISA kits. For
      the CBA 3-plex assay, the limits of detection (LODs) varied between 0.005 and
      0.363 ng/mL, the intra- and inter-assay coefficients of variation were <10% and
      <16%, respectively. For TNF-alpha, IL-1beta, IL-6 and pig-MAP, CBA time
      concentration profiles similar to those obtained with commercial ELISAs were
      observed. In conclusion, the novel validated CBA 3-plex assay provides a fast and
      economical screening tool for determination of pro-inflammatory cytokine profiles
      in limited porcine plasma volumes. This tool will be applied to study the
      immunomodulatory properties of drugs in a porcine LPS inflammation model. This
      study also demonstrated the applicability of CBA for measurement of APPs in pigs,
      although a different combination than pig-MAP with CRP is recommended.

PMID- 23159237
TI  - Intraocular vaccination with an inactivated highly pathogenic avian influenza
      virus induces protective antibody responses in chickens.
AB  - Because it is expected to induce cross-reactive serum and mucosal antibody
      responses, mucosal vaccination against highly pathogenic avian influenza (HPAI)
      is potentially superior to conventional parenteral vaccination. Here, we tested
      whether intraocular vaccination with an inactivated AI virus induced protective
      antibody responses in chickens. Chickens were inoculated intraocularly twice with
      10(4) hemagglutination units of an inactivated H5N1 HPAI virus. Four weeks after
      the second vaccination, the chickens were challenged with a lethal dose of the
      homologous H5N1 HPAI virus. Results showed that most of the vaccinated chickens
      mounted positive antibody responses. The median serum hemagglutination inhibition
      titer was 1:80. Addition of CpG oligodeoxynucleotide 2006 or cholera toxin to the
      vaccine did not enhance serum antibody titers. Cross-reactive anti-hemagglutinin
      IgG, but not IgA, was detected in oropharyngeal secretions. In accordance with
      these antibody results, most vaccinated chickens survived a lethal challenge with
      the H5N1 HPAI virus and did not shed the challenge virus in respiratory or
      digestive tract secretions. Our results show that intraocular vaccination with an
      inactivated AI virus induces not only systemic but also mucosal antibody
      responses and confers protection against HPAI in chickens.

PMID- 23159238
TI  - [Infection frequency in patients with chronic idiopathic ulcerative colitis].
AB  - BACKGROUND: Ulcerative Colitis (UC) is a chronic inflammatory bowel disease
      characterized by diffuse inflammation of the mucosa of the colon. Up to now,
      diverse observational studies have implicated a wide variety of pathogenic
      microorganisms as causal and exacerbating factors in UC. Clostridium difficile
      (C. difficile) infection has been associated with recurrence and treatment
      failure and its incidence in patients with UC has been on the rise in the last
      few years. AIMS: To determine the frequency of infection by different
      microorganisms in Mexican UC patients. PATIENTS AND METHODS: A total of 150
      patients with definitive UC diagnosis were studied. All the stool tests for
      parasites and ova, stool cultures, tests for the C. difficile toxins A and B, and
      immunohistochemistry for Cytomegalovirus in colon segment biopsies were analyzed.
      Other demographic and clinical variables of the disease were recorded for their
      correlation with infection frequency. RESULTS: Infection frequency in UC patients
      was 28.00%. C. difficile infection was present in 0.013%. Other pathogens were
      found, such as Endolimax nana (9.00%), Entamoeba histolytica (3.00%),
      Cytomegalovirus (2.00%), Salmonella (2.00%), Shigella (0.70%), Toxoplasma gondii
      (0.70%) and Iodamoeba butschlii (0.70%). CONCLUSIONS: Infection frequency was
      28.00% in our study and C. difficile infection represented only 0.013%.

PMID- 23159239
TI  - Factors associated with home discharge after rehabilitation among male veterans
      with lower extremity amputation.
AB  - OBJECTIVE: To determine the patient-, treatment-, and facility-level factors that
      are associated with home discharge among male veterans with lower extremity
      amputation who received inpatient rehabilitation after surgery. DESIGN: A
      retrospective observational study. SETTING: Veterans Affairs Medical Centers.
      PARTICIPANTS: This study included 1480 male veterans. METHODS: Generalized
      estimating equation models were used to model the likelihood of home discharge to
      account for within-facility clustering. We reported odds ratios (ORs) and 95%
      confidence intervals (95% CIs). MAIN OUTCOME MEASUREMENT: Discharged to home.
      RESULTS: There were a total of 1163 (78.6%) veterans who were discharged home
      after the surgical hospitalization, compared with other locations. Patients who
      were married were more likely to be discharged home compared with patients who
      were not married (OR = 1.51, 95% CI = 1.14-1.99, P < .01). Compared with being
      transferred from another hospital or extended care, patients who were admitted
      from home were far more likely to be discharged home (OR = 8.43, 95% CI = 5.48
      12.96, P < .0001). Patients with evidence of local significant infection were
      less likely to be discharged home (OR = 0.57, 95% CI = 0.39-0.83, P < .01), as
      were patients with evidence of congestive heart failure (OR = 0.62, 95% CI = 0.45
      0.85, P < .01) or depression (OR = 0.63, 95% CI = 0.40-0.98, P = .04). Veterans
      with greater discharge motor Functional Independence Measure scores were more
      likely to be discharged home (OR = 1.23, 95% CI = 1.16-1.31 per 10-point increase
      in discharge Functional Independence Measure motor score, P < .0001). Conversely,
      patients undergoing procedures for ongoing active cardiac pathology were less
      likely to be discharged home (OR = 0.55, 95% CI = 0.37-0.81, P < .01).
      CONCLUSIONS: This study showed a strong association between the sociological
      factors of marital status and living location before hospitalization and home
      discharge. The significance of discharge functional status highlights the
      importance of addressing the expected care burden once patients are discharged
      home.

PMID- 23159240
TI  - Defining the clinical syndrome of lumbar spinal stenosis: a recursive specialist
      survey process.
AB  - BACKGROUND: Lumbar spinal stenosis has evolved from an anatomic concept to a
      poorly defined clinical syndrome. Rules for such a syndrome need to be informed
      by the experience and beliefs of expert clinicians. The level of certainty is
      seldom considered in defining criteria for a syndrome. OBJECTIVE: To design an
      innovative online recursive survey technique to seek out information that is
      valued by specialists and to measure the impact of this evidence on their
      strength of conviction regarding the diagnosis of spinal stenosis. DESIGN:
      Prospective online survey. SETTING: University-based project. PARTICIPANTS:
      American physiatrists recruited by online postings and postcards. INTERVENTIONS:
      A recursive process presented a scenario that allowed clinicians to choose 1 of
      10 clinical factors and then asked their level of certainty about diagnosis when
      that factor is true. Subsequent questions build on that assumption by adding
      other factors. MAIN OUTCOME MEASURES: Certainty regarding the diagnosis of
      clinical lumbar spinal stenosis. RESULTS: Of a total of 97 participants, 80
      completed 3 or more iterations. "Leg pain while walking" (66%), "must sit down or
      bend" (66%), and "flex forward while walking" (49%) were the most commonly
      selected questions. "Normal foot pulses" (19%), "back pain" (16%), "leg pain"
      (15%), "relief with rest" (14%), and "sensory deficits" (12%) were of
      intermediate value, whereas "problems with balance," "have fallen recently," and
      "the sacroiliac joint is not the main pain generator" were all chosen less than
      5% of the time. Statistically significant (P < .05) change in certainty ceased
      after 6 questions at 86.2% certainty. CONCLUSIONS: A recursive approach to
      diagnostic certainty is valuable. Within 5 questions, clinicians become almost
      90% certain that a person has clinical spinal stenosis. This question set
      provides one pragmatic clinical criterion for the syndrome of lumbar spinal
      stenosis.

PMID- 23159241
TI  - Designing and implementing a system for tracking functional status after stroke:
      a feasibility study.
AB  - OBJECTIVE: To determine the feasibility of tracking stroke patients' functional
      outcomes in an integrated health system across a care continuum using the
      computer version of the Activity Measure of Post-Acute Care (AM-PAC). SETTING: A
      large integrated health care system in northern California. PARTICIPANTS: A total
      of 222 stroke patients (aged >=18 years) who were hospitalized after an acute
      cerebrovascular accident. METHODS: An AM-PAC assessment was made at discharge
      from sites of care, including acute hospital, inpatient rehabilitation hospital,
      skilled nursing facility, home during home care, and outpatient settings.
      Assessments also were completed in the patient's home at 6 months. Data from the
      AM-PAC program were integrated with the health care system's databases. MAIN
      OUTCOME MEASUREMENTS: (1) AM-PAC administration time at the various sites of
      care; (2) assessment of a floor or a ceiling effect; and (3) administrative
      burden of tracking participants. RESULTS: AM-PAC assessment sessions averaged 7.9
      minutes for data acquisition in 3 domains: Basic Mobility, Activities of Daily
      Living, and Applied Cognition. Participants answered, on average, 27 AM-PAC
      questions per session. A small ceiling effect was observed at 6 months, and there
      was a larger ceiling effect when the instrument was administered in an
      institution, ie, when the AM-PAC institutional item bank was used rather than the
      community item bank. It was feasible to track patients and to assess their
      function using the AM-PAC instrument from institutional to community settings.
      Implementation of the AM-PAC in clinical environments, and the success of the
      project, were influenced by instrumental, technological, operational, resource,
      and cultural factors. CONCLUSIONS: This study demonstrates the feasibility of
      implementing a single functional outcome instrument in clinical and community
      settings to measure rehabilitation functional outcomes of stroke patients.
      Integrating the AM-PAC measurement system into clinical workflows and the
      electronic medical record could provide assistance to clinicians for medical
      decision making, functional prognostication, and discharge planning.

PMID- 23159242
TI  - Practical wisdom: a qualitative study of the care and management of non-invasive
      ventilation patients by experienced intensive care nurses.
AB  - OBJECTIVES: To describe the reasoning and actions of experienced nurses caring
      for patients with non-invasive ventilation due to acute respiratory failure from
      chronic obstructive pulmonary disease. INTRODUCTION: Treatment success for
      patients requiring non-invasive ventilation remains challenging. Understanding
      the reasoning and actions of experienced nurses that care for patients with non
      invasive ventilation can identify how nurses contribute to treatment success, and
      this information can be used to train less experienced nurses to provide
      excellent care. DESIGN: Qualitative descriptive study. A secondary analysis on
      data of qualitative participant observations during non-invasive ventilation
      treatment and additional six interviews with experienced ICU nurses was carried
      out in 2012. RESULTS: The experienced nurses exhibited 'practical wisdom'. Each
      nurse could stay alert to the patient's condition and respond to NIV.
      Conceptualisation of the complexities in nurses' reasoning and actions
      illustrated their tendency to separate problematic situations into three
      interrelated components: (1) achieving non-invasive adaptation, (2) ensuring
      effective ventilation and (3) responding attentively to patients' perceptions of
      non-invasive ventilation. Each component comprises a set of nursing reasoning and
      actions that experienced nurses use to achieve treatment success. CONCLUSIONS:
      Understanding how experienced nurses think and act during non-invasive
      ventilation care may help to optimise continuing professional development and
      help educate junior nurses.

PMID- 23159243
TI  - Infectivity of rabies virus-exposed macrophages.
AB  - Rabies virus distributes widely in infected mice, including lymphoid tissues and
      spleen macrophages. The infection characteristics in murine macrophages and the
      infectivity of virus-exposed macrophages were examined upon inoculation in mice.
      In vitro, Mf4/4 spleen macrophages supported mild virus production (10(4)-fold
      less than neuroblastoma), with formation of typical virions. Bone marrow-derived
      macrophages (BMM) were most efficient to capture virus, but new virus production
      was not detected. Virus-induced cell death was significantly stronger in BMM,
      which might have eliminated BMM with productive infection. Still, viral RNA
      remained detectable in the remaining BMM for at least 4 weeks. Injection of in
      vitro-infected Mf4/4 in the nose or brain proved efficient to propagate infection
      in mice, even when cells were pre-incubated with neutralizing antibodies.
      Surprisingly, injection of ex-vivo-infected BMM in the brain also led to lethal
      infection in 8 out of 12 mice. Injection of infected Mf4/4 in the muscle mostly
      favoured a protective antibody response. Despite that macrophages are less fit to
      support virus production, they can still act as a source of infectious virus upon
      transfer in mice. This may be relevant for screening donor organs/cells, for
      which RT-PCR should be preferred over the traditional antigen or virus isolation
      assays.

PMID- 23159244
TI  - Deletion of invH gene in Salmonella enterica serovar Typhimurium limits the
      secretion of Sip effector proteins.
AB  - The type-III secretion system-I (T3SS-I) of Salmonella enterica serovar
      Typhimurium (S. Typhimurium) is an essential component to mediate active invasion
      and subsequent inflammation in genetically susceptible C57BL/6 mice. S.
      Typhimurium translocates its effector proteins through Salmonella Pathogenicity
      Island-I (SPI-I) encoded T3SS-I needle complex. This study focuses on invH gene
      of S. Typhimurium, which plays an active role in SPI-I mediated effector protein
      translocation. The deletion of invH gene in S. Typhimurium reduced the invasion
      efficiency of the bacterium to 70-80% as compared to wild-type S. Typhimurium
      (SB300) in vitro. To further investigate the role of invH gene exclusively in SPI
      1 mediated inflammation, C57BL/6 mice were infected with S. Typhimurium double
      mutant deficient in invH and ssaV. Results indicated significant difference in
      the degree of cecal inflammation between wild-type S. Typhimurium and double
      mutant at 12 h and 48 h post infection. However this difference was found to be
      more prominent at 12 h p.i. In line with our findings, analysis of effector
      protein secretion in invH, ssaV double mutant showed reduced secretion of Sip
      effector proteins (SipA, SipB, SipC and SipD) as compared to the wild-type
      strain. The inflammation phenotype was restored on complementing invH to its
      respective double mutant strain. Altogether, the current study proposes a
      possible role of invH gene in early cecal inflammation by Salmonella Typhimurium
      in mice colitis model.

PMID- 23159245
TI  - Interleukin-17 enhanced immunoinflammatory lesions in a mouse model of recurrent
      herpetic keratitis.
AB  - Interleukin-17 (IL-17), mainly produced by activated (memory) T cells, has been
      found in the corneas from herpetic stromal keratitis (HSK) patients. To better
      understand the role of IL-17 and to optimize fidelity to human recurrent HSK, in
      this study, we utilized a mouse model of recurrent HSK, examined the expression
      of IL-17 and Th17 cells, and determine the alterability of virus-induced corneal
      inflammation after anti-IL-17 antibody treatment during murine recurrent HSK. We
      found that Th17 cells were obviously up-regulated in both cornea and DLNs of
      recurrent mice. Peak IL-17 protein present in recurrent cornea in conjunction
      with peak opacity mediated by CD4(+) T cells. Systemic administration of anti-IL
      17 antibody resulted in a diminished severity of corneal opacity,
      neovascularization, and CD4(+) T cells infiltration compared to control. Anti-IL
      17 treatment down-regulated the mRNA and protein levels of TNF-alpha expression
      in recurrent corneas, and decreased HSV-specific DTH responses. Our results
      indicate that elevated IL-17 expression may be involved in the development of
      recurrent HSK. The likely mechanisms of action for IL-17 are through up
      regulating TNF-alpha expression and promoting HSV-specific DTH responses. Thus,
      IL-17 might constitute a useful target for therapeutic intervention in recurrent
      HSK.

PMID- 23159246
TI  - Sex-determining region Y-box 2 amplification in preneoplastic squamous lesions of
      the lung.
AB  - Sex-determining region Y-box 2 gene at 3q26.33 has been identified as oncogene in
      squamous cell carcinoma occurring at different anatomical sites including the
      lung. Sex-determining region Y-box 2 protein expression and gene amplification
      have been found in preinvasive squamous cell lesions such as dysplasia and
      carcinoma in situ. We sought to evaluate sex-determining region Y-box 2
      expression and amplification in a spectrum of premalignant squamous lesions
      ranging from squamous metaplasia to low- and high-grade dysplasia to in situ and
      invasive squamous cell carcinoma of the lung. Each lesion was taken from 1 of 3
      study groups: 18 patients with concurrent squamous cell carcinoma, 17 patients
      with prior squamous cell carcinoma undergoing surveillance biopsies, and 11
      patients with no history of squamous cell carcinoma. Sex-determining region Y-box
      2 amplification occurred only in a subset of invasive squamous cell carcinoma
      (3/5; 60%) and their associated high-grade dysplasia (3/4; 75%), but not in any
      of the low-grade dysplasias (0/1; 0%) or metaplasias (0/9; 0%). No sex
      determining region Y-box 2 amplification was observed in squamous preneoplastic
      lesions in surveillance biopsies without current evidence of squamous cell
      carcinoma or in benign lungs. Sex-determining region Y-box 2 protein expression
      was seen in all squamous lesions regardless of presence or degree of dysplasia.
      Our results suggest that sex-determining region Y-box 2 amplification is not an
      early event in squamous carcinogenesis and is important for progression in a
      subset of squamous cell carcinoma. It appears that sex-determining region Y-box 2
      gene amplification in lung squamous carcinogenesis is not the only regulator of
      sex-determining region Y-box 2 protein expression.

PMID- 23159247
TI  - Histologic findings on prostate needle core biopsies following cryotherapy as
      monotherapy for prostatic adenocarcinoma.
AB  - The histologic features seen in the prostate following cryotherapy can be highly
      variable. However, most previous studies were performed on specimens following
      salvage cryotherapy, which introduces additional confounding variables of the
      histologic changes after the other primary treatment modalities. We examined
      prostate needle core biopsies from a cohort of patients following cryotherapy as
      monotherapy for prostatic adenocarcinoma, to evaluate the true spectrum of
      morphologic changes in the prostate. Cases that had prior radiation therapy or
      androgen-deprivation therapy were excluded from the study. Thirty cases were
      identified. The average patient age was 69 years (range, 51-81 years), and the
      average time interval between cryotherapy and repeat biopsy was 19.2 months
      (range, 2-60 months). The original Gleason scores were as follows: 3 + 3 = 6 in
      14 (46%) of 30 cases, 3 + 4 = 7 in 8 (27%) of 30 cases, 4 + 3 = 7 in 2 (7%) of 30
      cases, 4 + 4 = 8 in 3 (10%) of 30 cases, 4 + 5 = 9 in 2 (7%) of 30 cases, and 5 +
      4 = 9 in 1 (3%) of 30 cases. Postcryotherapy, 11 of 30 cases (37%) had
      recurrent/residual prostatic adenocarcinoma, which showed no therapy-related
      changes, similar to the residual benign glands. Gleason scores were higher in 5
      (46%) of 11 cases, same in 4 (36%) of 11 cases, and lower in 2 (18%) of 11 cases.
      Multiple additional histologic findings were documented. Unlike other nonsurgical
      therapeutic modalities, cases with recurrent/residual prostatic adenocarcinoma
      and benign glands showed therapy-related changes predominantly involving the
      stroma. It is therefore conceivable that benign or malignant prostatic glands are
      either completely destroyed during cryotherapy or left unaltered if not in the
      direct field of cryoablation.

PMID- 23159248
TI  - Fatal thromboembolism to the left pulmonary artery by locally applied hemostatic
      matrix after surgical removal of spinal schwannoma: a case report.
AB  - Locally applied hemostatic agents, mostly consisting of gelatinous granules with
      admixed human or bovine thrombin, are used in various surgical procedures. In our
      case, a 78-year-old woman underwent neurosurgical removal of an extraforaminal
      schwannoma of the L5 dorsal root ganglion. During the procedure, the hemostatic
      matrix consisting of a meshwork of bovine gelatinous granules admixed with human
      thrombin was locally applied to control diffuse paravertebral bleeding. Eight
      hours after surgery, the patient developed dyspnea with right heart failure and
      finally died. At autopsy, we found complete occlusion of the left pulmonary
      artery with a large thromboembolus. Histologically, that thromboembolus consisted
      of gelatinous granules with only a thin rim of surrounding, classic parietal
      thrombus. To our knowledge, this is the first description of fatal pulmonary
      embolization of a major lung artery with this material. The report depicts a
      possible life-threatening complication associated with the local application of
      hemostatic agents.

PMID- 23159249
TI  - Recurrent de novo mutations in PACS1 cause defective cranial-neural-crest
      migration and define a recognizable intellectual-disability syndrome.
AB  - We studied two unrelated boys with intellectual disability (ID) and a striking
      facial resemblance suggestive of a hitherto unappreciated syndrome. Exome
      sequencing in both families identified identical de novo mutations in PACS1,
      suggestive of causality. To support these genetic findings and to understand the
      pathomechanism of the mutation, we studied the protein in vitro and in vivo.
      Altered PACS1 forms cytoplasmic aggregates in vitro with concomitant increased
      protein stability and shows impaired binding to an isoform-specific variant of
      TRPV4, but not the full-length protein. Furthermore, consistent with the human
      pathology, expression of mutant PACS1 mRNA in zebrafish embryos induces
      craniofacial defects most likely in a dominant-negative fashion. This phenotype
      is driven by aberrant specification and migration of SOX10-positive cranial, but
      not enteric, neural-crest cells. Our findings suggest that PACS1 is necessary for
      the formation of craniofacial structures and that perturbation of its functions
      results in a specific syndromic ID phenotype.

PMID- 23159251
TI  - An exponential combination procedure for set-based association tests in
      sequencing studies.
AB  - State-of-the-art next-generation-sequencing technologies can facilitate in-depth
      explorations of the human genome by investigating both common and rare variants.
      For the identification of genetic factors that are associated with disease risk
      or other complex phenotypes, methods have been proposed for jointly analyzing
      variants in a set (e.g., all coding SNPs in a gene). Variants in a properly
      defined set could be associated with risk or phenotype in a concerted fashion,
      and by accumulating information from them, one can improve power to detect
      genetic risk factors. Many set-based methods in the literature are based on
      statistics that can be written as the summation of variant statistics. Here, we
      propose taking the summation of the exponential of variant statistics as the set
      summary for association testing. From both Bayesian and frequentist perspectives,
      we provide theoretical justification for taking the sum of the exponential of
      variant statistics because it is particularly powerful for sparse alternatives
      that is, compared with the large number of variants being tested in a set, only
      relatively few variants are associated with disease risk-a distinctive feature of
      genetic data. We applied the exponential combination gene-based test to a
      sequencing study in anticancer pharmacogenomics and uncovered mechanistic
      insights into genes and pathways related to chemotherapeutic susceptibility for
      an important class of oncologic drugs.

PMID- 23159250
TI  - Copy-number disorders are a common cause of congenital kidney malformations.
AB  - We examined the burden of large, rare, copy-number variants (CNVs) in 192
      individuals with renal hypodysplasia (RHD) and replicated findings in 330 RHD
      cases from two independent cohorts. CNV distribution was significantly skewed
      toward larger gene-disrupting events in RHD cases compared to 4,733 ethnicity
      matched controls (p = 4.8 * 10(-11)). This excess was attributable to known and
      novel (i.e., not present in any database or in the literature) genomic disorders.
      All together, 55/522 (10.5%) RHD cases harbored 34 distinct known genomic
      disorders, which were detected in only 0.2% of 13,839 population controls (p =
      1.2 * 10(-58)). Another 32 (6.1%) RHD cases harbored large gene-disrupting CNVs
      that were absent from or extremely rare in the 13,839 population controls,
      identifying 38 potential novel or rare genomic disorders for this trait.
      Deletions at the HNF1B locus and the DiGeorge/velocardiofacial locus were most
      frequent. However, the majority of disorders were detected in a single
      individual. Genomic disorders were detected in 22.5% of individuals with multiple
      malformations and 14.5% of individuals with isolated urinary-tract defects; 14
      individuals harbored two or more diagnostic or rare CNVs. Strikingly, the
      majority of the known CNV disorders detected in the RHD cohort have previous
      associations with developmental delay or neuropsychiatric diseases. Up to 16.6%
      of individuals with kidney malformations had a molecular diagnosis attributable
      to a copy-number disorder, suggesting kidney malformations as a sentinel
      manifestation of pathogenic genomic imbalances. A search for pathogenic CNVs
      should be considered in this population for the diagnosis of their specific
      genomic disorders and for the evaluation of the potential for developmental
      delay.

PMID- 23159253
TI  - Breast and colorectal cancer screening: U.S. primary care physicians' reports of
      barriers.
AB  - BACKGROUND: Primary care physicians (PCPs) play a key role in performing and
      referring patients for cancer screening. Understanding barriers to test use is
      critical to developing strategies that promote adherence to clinical guidelines,
      but current literature does not distinguish the extent to which barriers may be
      similar or unique across screening modalities. PURPOSE: To describe PCPs' self
      reported perceptions of barriers to screening for breast and colorectal cancer
      (CRC) and compare the top three barriers associated with these screening
      modalities. METHODS: Cross-sectional data analyzed in 2011 from a nationally
      representative survey of 2478 PCPs in the U.S. in 2006-2007. RESULTS: PCPs
      reported greater barriers for CRC screening than for mammography. Lack of patient
      follow-through to complete recommended screening and the inability to pay for
      tests were the main barriers perceived by PCPs for both types of screening.
      Another major barrier cited was that patients do not perceive CRC as a threat.
      This was a lesser concern for the well-diffused message about the need for
      mammography. CONCLUSIONS: This is the first national study to provide a
      comparison of physician-perceived barriers to breast and CRC screening. Study
      results suggest that efforts to improve use of cancer screening, and CRC
      screening in particular, will require interventions at physician, practice, and
      health-system levels.

PMID- 23159252
TI  - Aid-assisted decision making and colorectal cancer screening: a randomized
      controlled trial.
AB  - BACKGROUND: Shared decision making (SDM) is a widely recommended yet unproven
      strategy for increasing colorectal cancer (CRC) screening uptake. Previous trials
      of decision aids to increase SDM and CRC screening uptake have yielded mixed
      results. PURPOSE: To assess the impact of decision aid-assisted SDM on CRC
      screening uptake. DESIGN: RCT. SETTING/PARTICIPANTS: The study was conducted at
      an urban, academic safety-net hospital and community health center between 2005
      and 2010. Participants were asymptomatic, average-risk patients aged 50-75 years
      due for CRC screening. INTERVENTION: Study participants (n=825) were randomized
      to one of two intervention arms (decision aid plus personalized risk assessment
      or decision aid alone) or control arm. The interventions took place just prior to
      a routine office visit with their primary care providers. MAIN OUTCOME MEASURES:
      The primary outcome was completion of a CRC screening test within 12 months of
      the study visit. Logistic regression was used to identify predictors of test
      completion and mediators of the intervention effect. Analysis was completed in
      2011. RESULTS: Patients in the decision-aid group were more likely to complete a
      screening test than control patients (43.1% vs 34.8%, p=0.046) within 12 months
      of the study visit; conversely, test uptake for the decision aid and decision aid
      plus personalized risk assessment arms was similar (43.1% vs 37.1%, p=0.15).
      Assignment to the decision-aid arm (AOR=1.48, 95% CI=1.04, 2.10), black race
      (AOR=1.52, 95% CI=1.12, 2.06) and a preference for a patient-dominant decision
      making approach (AOR=1.55, 95% CI=1.02, 2.35) were independent determinants of
      test completion. Activation of the screening discussion and enhanced screening
      intentions mediated the intervention effect. CONCLUSIONS: Decision aid-assisted
      SDM has a modest impact on CRC screening uptake. A decision aid plus personalized
      risk assessment tool is no more effective than a decision aid alone. TRIAL
      REGISTRATION: This study is registered at www.clinicaltrials.govNCT00251862.

PMID- 23159254
TI  - Cigarette warning label policy alternatives and smoking-related health
      disparities.
AB  - BACKGROUND: Pictorial health warning labels on cigarette packaging have been
      proposed for the U.S., but their potential influences among populations that
      suffer tobacco-related health disparities are unknown. PURPOSE: To evaluate
      pictorial health warning labels, including moderation of their influences by
      health literacy and race. METHODS: From July 2011 to January 2012, field
      experiments were conducted with 981 adult smokers who were randomized to control
      (i.e., text-only labels, n=207) and experimental conditions (i.e., pictorial
      labels, n=774). The experimental condition systematically varied health warning
      label stimuli by health topic and image type. Linear mixed effects (LME) models
      estimated the influence of health warning label characteristics and participant
      characteristics on label ratings. Data were analyzed from January 2012 to April
      2012. RESULTS: Compared to text-only warning labels, pictorial warning labels
      were rated as more personally relevant (5.7 vs 6.8, p<0.001) and effective (5.4
      vs 6.8, p<0.001), and as more credible, but only among participants with low
      health literacy (7.6 vs 8.2, p<0.001). Within the experimental condition,
      pictorial health warning labels with graphic imagery had significantly higher
      ratings of credibility, personal relevance, and effectiveness than imagery of
      human suffering and symbolic imagery. Significant interactions indicated that
      labels with graphic imagery produced minimal differences in ratings across racial
      groups and levels of health literacy, whereas other imagery produced greater
      group differences. CONCLUSIONS: Pictorial health warning labels with graphic
      images have the most-pronounced short-term impacts on adult smokers, including
      smokers from groups that have in the past been hard to reach.

PMID- 23159255
TI  - Smoking in context: a multilevel analysis of 49,088 communities in Canada.
AB  - BACKGROUND: The extent to which the prevalence of smoking in Canada varies across
      geographic areas independently of individual characteristics has not been
      quantified. PURPOSE: To estimate the extent and potential sources of geographic
      variation in smoking among communities, health regions, and provinces/territories
      in Canada. METHODS: Data are from the Canadian Community Health Surveys conducted
      between 2001 and 2008 (n=461,709). Current cigarette smoking among adults (aged
      >=18 years) was the primary outcome. Individual-level markers of SES were
      education, household income, and occupation. Contextual variables potentially
      related to smoking considered were provincial cigarette taxes, workplace smoking
      bans, and collective family norms discouraging smoking in communities. A
      multilevel logistic regression analysis was conducted to model variation in
      smoking at the geographic scale of communities, health regions, and provinces.
      RESULTS: Overall, the contribution of geography as a percentage of the total
      variation in smoking was 8.4%, with 2.4% attributable to provinces, 1.2%
      attributable to health regions, and 4.8% attributable to communities after
      adjusting for age, gender and survey period. In models that accounted for
      socioeconomic and demographic characteristics in addition to age and gender, the
      contribution of geography to the total variation in smoking was attenuated to
      4.1%; with 2.0% at the province level, 0.4% at the health region level, and 1.7%
      at the community level. Within provinces/territories, the community variation in
      smoking ranged from 2.4% in Prince Edward Island to 9.1% in British Columbia.
      Nationally, 71% of community and 21% of provincial differences in smoking were
      explained by individual, socioeconomic, and demographic factors alone; the
      inclusion of contextual covariates explained an additional 27% of the variation
      among communities. Collective family norms discouraging smoking in a community
      was the strongest contextual predictor of individual smoking; provincial
      cigarette taxes and workplace bans were only modestly related to individual
      smoking behavior. CONCLUSIONS: Geographic variation in smoking remained after
      accounting for individual, socioeconomic, and demographic characteristics,
      suggesting the importance of place, at the level of provinces and communities in
      Canada. Remaining community variation in smoking was largely attenuated after
      accounting for collective family norms discouraging smoking. Area-level
      influences such as the social and/or environmental conditions of provinces and
      communities may be important sources of variation in smoking and therefore need
      to be considered if rates of smoking are to be modified.

PMID- 23159257
TI  - Active transportation and cardiovascular disease risk factors in U.S. adults.
AB  - BACKGROUND: Evidence of associations between active transportation (walking and
      bicycling for transportation) and health outcomes is limited. Better
      understanding of this relationship would inform efforts to increase physical
      activity by promoting active transportation. PURPOSE: This study examined
      associations between active transportation and cardiovascular disease risk
      factors in U.S. adults. METHODS: Using the 2007-2008 and 2009-2010 cycles of the
      National Health and Nutrition Examination Survey (NHANES), adults (N=9933) were
      classified by level of active transportation. Multivariable linear and logistic
      regression analyses controlled for sociodemographic characteristics, smoking
      status, and minutes/week of non-active transportation physical activity. Analyses
      were conducted in 2011. RESULTS: Overall, 76% reported no active transportation.
      Compared with no active transportation, mean BMI was lower among individuals with
      low (-0.9, 95% CI= -1.4, -0.5) and high (-1.2, 95% CI= -1.7, -0.8) levels of
      active transportation. Mean waist circumference was lower in the low (-2.2 cm,
      95% CI= -3.2, -1.2) and high (-3.1 cm, 95% CI= -4.3, -1.9) active transportation
      groups. The odds of hypertension were 24% lower (AOR=0.76, 95% CI=0.61, 0.94) and
      31% lower (AOR=0.69, 95% CI=0.58, 0.83) among individuals with low and high
      levels of active transportation, respectively, compared with no active
      transportation. High active transportation was associated with 31% lower odds of
      diabetes (AOR=0.69, 95% CI=0.54, 0.88). Active transportation was not associated
      with high-density lipoprotein level. CONCLUSIONS: Active transportation was
      associated with more-favorable cardiovascular risk factor profiles, providing
      additional justification for infrastructure and policies that permit and
      encourage active transportation.

PMID- 23159256
TI  - Inflammation and early-life abuse in women.
AB  - BACKGROUND: Abuse in childhood and adolescence may affect risks of diabetes and
      cardiovascular disease later in life. Although mechanisms underlying these
      relationships are unclear, chronic stress may lead to dysregulation of immune
      function and chronic inflammation. PURPOSE: To evaluate associations between
      early-life physical and sexual abuse and blood levels of inflammatory markers in
      adulthood among 702 members of the Nurses' Health Study II. METHODS: Abuse in
      childhood (before age 11 years) and adolescence (ages 11-17 years) was self
      reported in 2001. Plasma samples collected in 1996-1999 were assayed for C
      reactive protein (CRP); interleukin (IL)-6; and the soluble fraction of tumor
      necrosis factor alpha receptor 2 in 2001, 2009, and 2010. RESULTS: Mean age at
      blood collection was 43.9 years. Moderate or severe physical abuse was reported
      by 35.3% of participants; 22.7% reported unwanted sexual touching and 9.8%
      reported forced sex. Plasma levels of CRP and IL-6 were higher in women reporting
      sexual abuse in adolescence compared to those reporting no abuse (p=0.04 and
      0.03, respectively) in analyses adjusted for confounders including age and
      childhood adiposity. Inflammatory marker levels similarly were elevated in women
      reporting sexual abuse during childhood, but results were not significant.
      Relationships largely persisted after further adjustment for potential mediators
      such as adult BMI and smoking. Physical abuse during childhood and/or adolescence
      was not consistently associated with inflammatory marker levels. CONCLUSIONS:
      Chronic inflammation may be one mechanism through which sexual abuse may affect
      future risk of physical and psychological disorders.

PMID- 23159258
TI  - Exercise training and habitual physical activity: a randomized controlled trial.
AB  - BACKGROUND: Exercise training reduces adiposity and risk of cardiovascular
      disease. However, the combined effects of habitual free-living physical activity
      and aerobic training on waist circumference, weight, fitness, and blood pressure
      in postmenopausal women are unknown. PURPOSE: To evaluate the effects of habitual
      physical activity levels during aerobic training on weight, waist circumference,
      fitness, and blood pressure. DESIGN: Secondary analysis of an RCT. Original data
      collected April 2001 to June 2005 and analyzed in 2012. SETTING/PARTICIPANTS:
      Postmenopausal women in a supervised exercise trial. INTERVENTION: Women (n=325)
      were randomized to 4, 8, or 12 kcal/kg per week of aerobic training or a control
      group for 6 months. All outcome measures were collected at baseline and follow
      up. Changes in dependent variables within each training group were evaluated
      across tertiles of pedometer-determined habitual physical activity outside
      exercise training sessions. MAIN OUTCOME MEASURES: Changes in waist circumference
      and weight. RESULTS: Reductions in waist circumference were significantly greater
      with higher steps/day accumulated outside exercise training compared to lower
      levels in the 4 (high: -4.8 cm vs low: -1.4 cm, p=0.03); 8 (high: -4.2 cm vs low:
      -0.4 cm, p=0.03), and 12 kcal/kg per week groups (high: -4.1 cm vs low: -0.7 cm,
      p=0.05). For all groups, p-trend<=0.03. A trend was observed for greater weight
      reduction with higher steps/day in the 4 kcal/kg per week group (p-trend=0.04)
      but not for the other exercise doses. No effects were observed for blood pressure
      or fitness measures (all p>0.05). CONCLUSIONS: In postmenopausal women, higher
      habitual physical activity while participating in aerobic training was associated
      with greater reductions in central adiposity, and was supportive of weight loss
      compared to lower levels.

PMID- 23159259
TI  - Social network analysis of childhood and youth physical activity: a systematic
      review.
AB  - CONTEXT: Social network analysis has been used to better understand the influence
      of friends and peer groups in a wide range of health behaviors. This systematic
      review synthesizes findings from various social network analyses of child and
      adolescent physical activity, to determine the extent to which social network
      structure is associated with physical activity behaviors. EVIDENCE ACQUISITION:
      Medical and social science databases were searched and screened between September
      and November 2011. Eligible studies collected a measure of physical activity and
      a measure of an individual's social network, either through friendship
      nominations or social ratings, and reported analyses investigating the
      association between physical activity and the social network measure. EVIDENCE
      SYNTHESIS: A total of 1767 articles yielded nine publications from seven eligible
      studies, which were synthesized and analyzed in December 2011. Three research
      themes were identified: (1) friendship similarities in physical activity; (2)
      peer group influences on physical activity; and (3) social preference (i.e.,
      popularity) and physical activity. Synthesis of findings across studies found
      strong evidence for similarities in physical activity levels between an
      individual and their friends and within peer groups. There was mixed evidence for
      an association between social preference and physical activity levels.
      CONCLUSIONS: Friendship plays an important role in shaping physical activity
      behaviors. Physical activity interventions targeted at peer groups and that
      account for the influence of friendship groups might have utility as a means of
      increasing youth physical activity.

PMID- 23159260
TI  - Physical activity policies and legislation in schools: a systematic review.
AB  - CONTEXT: Current physical activity levels of youth are alarmingly low. One way to
      promote higher levels of physical activity to youth is through school-based
      government policies. The current review examines evaluation of school-based
      physical activity policies for youth over the past 10 years. EVIDENCE
      ACQUISITION: Articles included met the following criteria: was an original
      research study published in an academic journal in English; examined or was
      related to physical activity behavior; applied to a youth population in a school
      setting; highlighted a law, bill, or policy reflective of physical activity based
      on government initiatives; and involved an evaluation. After searching five
      databases in January 2011, a total of 13 articles were selected for inclusion.
      EVIDENCE SYNTHESIS: All policies came from the U.S.; seven studies highlighted
      the federal Child Nutrition and Women, Infants, and Children Reauthorization Act
      of 2004 whereas the other six studies highlighted state-level policies dealing
      with safe routes to schools, physical activity-only initiatives, or physical
      activity as well as other initiatives. Eight articles evaluated policy
      implementation, three examined policy implementation and impact, and two articles
      considered only policy impact. CONCLUSIONS: This evaluation of the impact of
      policies on school-based physical activity indicates that such policies can
      affect health outcomes, specifically by increasing levels of physical activity.
      This study highlights the value of policy reform and calls attention to the need
      for independent evaluation of such policies.

PMID- 23159261
TI  - A health dividend for America: the opportunity cost of excess medical
      expenditures.

PMID- 23159262
TI  - The National Center on Birth Defects and Developmental Disabilities: past,
      present, and future.

PMID- 23159264
TI  - Financial incentives to promote active travel: an evidence review and economic
      framework.
AB  - CONTEXT: Financial incentives, including taxes and subsidies, can be used to
      encourage behavior change. They are common in transport policy for tackling
      externalities associated with use of motor vehicles, and in public health for
      influencing alcohol consumption and smoking behaviors. Financial incentives also
      offer policymakers a compromise between "nudging," which may be insufficient for
      changing habitual behavior, and regulations that restrict individual choice.
      EVIDENCE ACQUISITION: The literature review identified studies published between
      January 1997 and January 2012 of financial incentives relating to any mode of
      travel in which the impact on active travel, physical activity, or obesity levels
      was reported. It encompassed macroenvironmental schemes, such as gasoline taxes,
      and microenvironmental schemes, such as employer-subsidized bicycles. Five
      relevant reviews and 20 primary studies (of which nine were not included in the
      reviews) were identified. EVIDENCE SYNTHESIS: The results show that more-robust
      evidence is required if policymakers are to maximize the health impact of fiscal
      policy relating to transport schemes of this kind. CONCLUSIONS: Drawing on a
      literature review and insights from the SLOTH (sleep, leisure, occupation,
      transportation, and home-based activities) time-budget model, this paper argues
      that financial incentives may have a larger role in promoting walking and cycling
      than is acknowledged generally.

PMID- 23159265
TI  - The impact of clinical stage on prostate cancer survival following radical
      prostatectomy.
AB  - PURPOSE: Clinical stage has been incorporated into multiple risk stratification
      models for patients with newly diagnosed prostate cancer. However, the
      independent prognostic value of this variable remains open to debate. In this
      study we evaluated the association of clinical stage with death from prostate
      cancer in men who underwent radical prostatectomy and assessed for changes in its
      prognostic value over time. MATERIALS AND METHODS: We reviewed the records of
      14,842 consecutive patients who underwent radical prostatectomy at our
      institution between 1970 and 2008 without having received preoperative hormone or
      radiation therapy. Postoperative disease recurrence was estimated using the
      Kaplan-Meier method and compared using the log rank test. Multivariate Cox
      proportional hazard regression models were used to analyze the association of
      clinical stage with outcome. RESULTS: A total of 5,725 (38.6%) men were
      classified as having cT1 tumors, 8,160 (55.0%) cT2 tumors and 957 (6.4%) cT3
      disease. On univariate analysis clinical stage was significantly associated with
      postoperative biochemical recurrence, systemic progression and death from
      prostate cancer (p <0.001 for each). Moreover on multivariate analysis clinical
      stage was significantly associated with death from cancer for patients treated
      before (1.45, p = 0.006) and those treated during (1.96, p <0.001) the prostate
      specific antigen era. Furthermore, the incorporation of clinical stage into
      contemporary risk stratification improved the prediction of cancer specific
      survival (c statistic 0.782 without and 0.802 with clinical stage). CONCLUSIONS:
      Clinical stage is significantly associated with systemic progression and death
      from prostate cancer. Inclusion of this variable in multivariate prediction
      models improves the prediction of systemic progression and cancer specific
      survival.

PMID- 23159266
TI  - Re: undescended testis histology correlation with adult hormone levels and semen
      analysis.

PMID- 23159267
TI  - Undescended Testis Histology Correlation with Adult Hormone Levels and Semen
      Analysis.

PMID- 23159268
TI  - Dextranomer/hyaluronic acid endoscopic injection is effective in the treatment of
      intermediate and high grade vesicoureteral reflux in patients with complete
      duplex systems.
AB  - PURPOSE: Endoscopic subureteral injection of dextranomer/hyaluronic acid has
      become an established alternative to long-term antibiotic prophylaxis or surgical
      treatment for vesicoureteral reflux. We evaluated the effectiveness of endoscopic
      injection of dextranomer/hyaluronic acid in intermediate and high grade
      vesicoureteral reflux in patients with complete duplex collecting systems.
      MATERIALS AND METHODS: A total of 123 children underwent endoscopic correction of
      intermediate or high grade vesicoureteral reflux using injection of
      dextranomer/hyaluronic acid into complete duplex systems between 2001 and 2010.
      Vesicoureteral reflux was diagnosed by voiding cystourethrogram, and dimercapto
      succinic acid scan was performed to evaluate the presence of renal scarring.
      Followup ultrasound and voiding cystourethrogram were performed 3 months after
      the outpatient procedure and renal ultrasound thereafter every 2 years. Mean
      followup was 6.7 years. RESULTS: Complete duplex systems were unilateral in 110
      patients and bilateral in 13. Reflux severity in the 136 refluxing units was
      grade II in 1 (0.7%), III in 52 (38.2%), IV in 61 (44.9%) and V in 22 (16.2%).
      Dimercapto-succinic acid scan revealed renal functional abnormalities in 63
      children (51.2%). Vesicoureteral reflux resolved after the first endoscopic
      injection of dextranomer/hyaluronic acid in 93 ureters (68.4%), after a second
      injection in 35 (25.7%) and after a third injection in 8 (5.9%). Febrile urinary
      tract infection developed in 5 patients (4.1%) during followup. No patient
      required ureteral reimplantation or experienced significant complications.
      CONCLUSIONS: Our results confirm the safety and efficacy of endoscopic injection
      of dextranomer/hyaluronic acid in eradicating intermediate and high grade
      vesicoureteral reflux in patients with complete duplex systems. We recommend this
      minimally invasive, 15-minute outpatient procedure as a viable option for
      treating intermediate and high grade vesicoureteral reflux in patients with
      complete duplex collecting systems.

PMID- 23159270
TI  - Patterns and predictors of urodynamics use in the United States.
AB  - PURPOSE: Due to the paucity of data on urodynamics on the national level, we
      assessed the use of urodynamics in a large sample of individuals in the United
      States and identified predictors of increased complexity of urodynamic
      procedures. MATERIALS AND METHODS: Using administrative health care claims for
      adults enrolled in private insurance plans in the United States from 2002 to
      2007, we identified those who underwent cystometrogram and abstracted relevant
      demographic and clinical data. We used logistic regression to identify predictors
      of higher urodynamic complexity over basic cystometrogram, specifically
      cystometrogram plus pressure flow study and videourodynamics. RESULTS: We
      identified 16,574 urodynamic studies, of which 23% were cystometrograms, 71% were
      cystometrograms plus pressure flow studies and 6% were videourodynamics. Stress
      incontinence was the most common clinical condition for all studies (33.7%),
      cystometrogram (30.8%), cystometrogram plus pressure flow study (35.4%) and
      videourodynamics (24.4%). Urologists performed 59.8% of all urodynamics and
      gynecologists performed 35.5%. Providers with 14 or more urodynamic studies
      during the study period performed 75% of all urodynamics and were more likely to
      perform cystometrogram plus pressure flow study and videourodynamics. On
      regression analysis the most consistent predictors of cystometrogram plus
      pressure flow study and/or videourodynamics over cystometrogram were specialty
      (urologist) and the number of urodynamic tests performed by the provider.
      CONCLUSIONS: Most urodynamics in this series consisted of cystometrogram plus
      pressure flow study with stress incontinence the most common diagnosis. However,
      regardless of diagnosis, urologists and providers who performed more urodynamics
      were more likely to perform pressure flow study and/or videourodynamics in
      addition to cystometrogram. Further research is needed to determine whether these
      differences reflect gaps in the consistency or appropriateness of using
      urodynamics.

PMID- 23159271
TI  - Robotic salvage prostatectomy: underused but not for the inexperienced.

PMID- 23159272
TI  - Pathogenesis of nephrolithiasis.

PMID- 23159273
TI  - Kidney stone formation is positively associated with conventional risk factors
      for coronary heart disease in Japanese men.
AB  - PURPOSE: We investigated the association between kidney stones and coronary heart
      disease risk factors in Japanese men. MATERIALS AND METHODS: This cross-sectional
      study included 13,418 Japanese men 30 to 69 years old who voluntarily underwent
      medical examination between April 1995 and March 2001. Participants were divided
      into controls, and past and current kidney stone formers based on ultrasound
      results and medical history. We evaluated conventional risk factors of coronary
      heart disease, including overweight/obesity, hypertension, diabetes mellitus,
      gout/hyperuricemia, dyslipidemia and chronic kidney disease. Associations between
      coronary heart disease risk factors and kidney stones were investigated. RESULTS:
      Of the 13,418 participants 404 current kidney stone formers (3.0%) had kidney
      stones on ultrasound and 1,231 past kidney stone formers (9.2%) had a history of
      kidney stones but no kidney stones on medical examination. Body mass index,
      systolic and diastolic blood pressure, and serum uric acid were significantly
      higher in past and current kidney stone formers than in controls. Logistic
      regression analysis indicated that the multivariate adjusted OR for
      overweight/obesity, hypertension, gout/hyperuricemia and chronic kidney disease
      significantly increased in the order corresponding to controls, and past and
      current kidney stone formers. CONCLUSIONS: Kidney stone formers, even past stone
      formers, are likely to have accumulated risk factors for coronary heart disease.
      They could be preferentially targeted for coronary heart disease prevention.

PMID- 23159274
TI  - New treatments for painful urological conditions.

PMID- 23159275
TI  - The effect of the 5-HT2A/2C receptor agonist DOI on micturition in rats with
      chronic spinal cord injury.
AB  - PURPOSE: We examined the effects of the 5-HT2A/2C receptor agonist DOI on
      micturition in chronic spinal cord injured rats. MATERIALS AND METHODS: Female
      Sprague-Dawley(r) rats were used. Spinal cord injury was produced by transection
      at the T10 level. A cystometric study was performed 8 to 12 weeks after
      transection. Cystometrograms were done using urethane anesthesia in all rats. The
      selective 5-HT2A antagonist ketanserin was administered after each DOI dose
      response curve. All drugs were administered intravenously. RESULTS: Compared to
      controls, spinal cord injured rats had higher bladder capacity and post-void
      residual urine volume, and lower voiding efficiency. In spinal cord injured rats
      DOI (0.01 to 0.3 mg/kg) induced significant dose dependent increases in
      micturition volume and decreases in residual volume, resulting in increased
      voiding efficiency. Cystometrogram measurements showed a dose dependent increase
      in high frequency oscillation activity, evident as an increased number of small
      oscillation per voiding. This correlated with the improved voiding efficiency.
      Ketanserin (0.1 mg/kg) partially or completely reversed the DOI induced changes.
      CONCLUSIONS: High frequency oscillation seems to reflect external urethral
      sphincter burst activity during voiding. Bladder voiding efficiency and high
      frequency oscillation activity were decreased in spinal cord injured rats. High
      frequency oscillation activity can be enhanced by 5-HT2A receptor agonism,
      improving voiding efficiency. To our knowledge it remains to be studied whether
      these results may have implications for the future treatment of voiding
      dysfunction in patients with spinal cord injury.

PMID- 23159276
TI  - Efficacy and safety of flexible dose fesoterodine in men and women with
      overactive bladder symptoms including nocturnal urinary urgency.
AB  - PURPOSE: Awakening from sleep to urinate is the hallmark of nocturia, a condition
      that impacts several facets of health related quality of life and for which
      current therapy is suboptimal. Given the paucity of prospective data on
      antimuscarinics for the management of nocturia, we investigated the efficacy and
      safety of flexible dose fesoterodine for the treatment of nocturnal urgency in
      subjects with nocturia and overactive bladder. MATERIALS AND METHODS: Subjects
      with 2 to 8 nocturnal urgency episodes per 24 hours began a 2-week, single-blind,
      placebo run-in followed by 1:1 randomization to 12 weeks of double-blind
      treatment with fesoterodine (4 mg daily for 4 weeks with an optional increase to
      8 mg) or placebo using predefined criteria for nocturnal urgency episodes,
      nocturnal urine volume voided and total 24-hour urine volume voided. The primary
      end point was change from baseline to week 12 in the mean number of micturition
      related nocturnal urgency episodes per 24 hours. RESULTS: Overall 963 subjects
      were randomized from 2,990 screened, and 82% of subjects treated with
      fesoterodine and 84% of those treated with placebo completed the study.
      Significant improvements in the primary end point (-1.28 vs -1.07), in nocturnal
      micturitions per 24 hours (-1.02 vs -0.85) and in nocturnal frequency urgency sum
      (-4.01 vs -3.42) were observed with fesoterodine vs placebo (all p <=0.01).
      Health related quality of life measures (overactive bladder questionnaire Symptom
      Bother -20.1 vs -16.5, sleep 22.3 vs 19.9 and other domains; all p <0.05) were
      improved with fesoterodine. CONCLUSIONS: To our knowledge this is the first
      prospective study to assess antimuscarinic efficacy for reducing nocturnal
      urgency. Flexible dose fesoterodine significantly reduced nocturnal urgency
      episodes vs placebo in subjects with overactive bladder.

PMID- 23159278
TI  - Increased occurrence of disorders of sex development, prematurity and
      intrauterine growth restriction in children with proximal hypospadias associated
      with undescended testes.
AB  - PURPOSE: Proximal hypospadias represents 20% of hypospadias cases, which are
      considered to have a higher incidence of associated urological, nonurological,
      developmental and sexual development disorders, and chromosomal anomalies. We
      compared associated anomalies in boys with proximal hypospadias and undescended
      testis with those in boys with proximal hypospadias and descended testes.
      MATERIALS AND METHODS: We reviewed the medical records of 69 boys who underwent 2
      stage hypospadias repair for proximal hypospadias at a single institution during
      the 11-year period of 2001 to 2011. Collected data included demographics, birth
      history, associated urological and extra-urological anomalies, karyotype analysis
      and gonad palpability. Patients were divided into group 1-those with proximal
      hypospadias and undescended testis, and group 2-those with proximal hypospadias
      and descended testes. Statistical analysis was performed using the 2-tailed
      Fisher exact test. RESULTS: There were 17 patients (25%) in group 1 with a median
      age of 2.2 years and 52 in group 2 (75%) with a median age of 2 years. Children
      in group 1 had a higher incidence of XY nondysgenetic testicular sexual
      development disorder (8 vs 11, p = 0.06), premature birth (9 vs 10, p = 0.01) and
      intrauterine growth restriction (8 each) than children in group 2 (p = 0.01).
      CONCLUSIONS: Prematurity and intrauterine growth restriction are significantly
      associated with proximal hypospadias and undescended testis. Also, due to the 28%
      incidence of an underlying sexual development disorder, male infants with
      proximal hypospadias should undergo multidisciplinary evaluation.

PMID- 23159277
TI  - Expression of vesicular glutamate transporters in sensory and autonomic neurons
      innervating the mouse bladder.
AB  - PURPOSE: VGLUTs, which are essential for loading glutamate into synaptic
      vesicles, are present in various neuronal systems. However, to our knowledge the
      expression of VGLUTs in neurons innervating the bladder has not yet been
      analyzed. We studied VGLUT1, VGLUT2 and VGLUT3 in mouse bladder neurons.
      MATERIALS AND METHODS: We analyzed the expression of VGLUT1, VGLUT2 and
      calcitonin gene-related peptide by immunohistochemistry in the retrograde labeled
      primary afferent and autonomic neurons of BALB/c mice after injecting fast blue
      in the bladder wall. To study VGLUT3 we traced the bladder of transgenic mice, in
      which VGLUT3 is identified by enhanced green fluorescent protein detection.
      RESULTS: Most bladder dorsal root ganglion neurons expressed VGLUT2. A smaller
      percentage of neurons also expressed VGLUT1 or VGLUT3. Co-expression with
      calcitonin gene-related peptide was only observed for VGLUT2. Occasional VGLUT2
      immunoreactive neurons were seen in the major pelvic ganglia. Abundant VGLUT2
      immunoreactive nerves were detected in the bladder dome and trigone, and the
      urethra. VGLUT1 immunoreactive nerves were discretely present. CONCLUSIONS: We
      present what are to our knowledge novel data on VGLUT expression in sensory and
      autonomic neurons innervating the mouse bladder. The frequent association of
      VGLUT2 and calcitonin gene-related peptide in sensory neurons suggests
      interactions between glutamatergic and peptidergic neurotransmissions,
      potentially influencing commonly perceived sensations in the bladder, such as
      discomfort and pain.

PMID- 23159279
TI  - Adenocarcinoma in an ileal conduit.

PMID- 23159281
TI  - Circulating gamma/delta T cells in systemic sclerosis exhibit activated phenotype
      and enhance gene expression of proalpha2(I) collagen of fibroblasts.
AB  - BACKGROUND: Systemic sclerosis (SSc) is a systemic inflammatory and fibrotic
      disease characterized by activation of circulating T lymphocytes. OBJECTIVE: To
      determine phenotypic abnormalities of gamma/delta T cells and whether gamma/delta
      T cells influence fibroblasts activation in SSc patients. METHODS: Number and
      proportion of peripheral gamma/delta T lymphocytes, and their expressions of cell
      surface molecules were evaluated by flow cytometry. Isolated gamma/delta T cells
      were cocultured with fibroblast, and mRNA expressions of proalpha1(I) collagen
      and proalpha2(I) collagen (COL1A2) of fibroblasts were analyzed by real time RT
      PCR. gamma/delta T cell infiltrations in the skin were examined
      histopathologically. RESULTS: No significant difference in number and proportion
      of gamma/delta T cells was observed in SSc patients compared to healthy controls
      (HCs). Geometric mean fluorescence intensity (GMFI) of CD16 and CD69 on
      gamma/delta T cells was significantly increased in patients with diffuse
      cutaneous SSc (dcSSc) compared to HCs. CD62L expression was significantly
      decreased in patients with dcSSc compared to HCs. The percentage of CD69 positive
      gamma/delta T cells was significantly higher in patients with SSc than HCs.
      COL1A2 mRNA expression was significantly higher in fibroblasts cocultured with
      gamma/delta T cells from SSc than that from HCs in cell contact independent
      manner. Additionally, gamma/delta T cell infiltrations were observed in SSc
      patients' skin. CONCLUSION: Our results suggest that gamma/delta T cells showed
      activated phenotype in SSc and suggest that SSc gamma/delta T cells may play an
      important role on fibrotic process by upregulation of COL1A2 mRNA expression in
      fibroblasts.

PMID- 23159282
TI  - In vivo and in vitro evaluation of the use of a newly developed melatonin loaded
      emulsion combined with UV filters as a protective agent against skin irradiation.
AB  - BACKGROUND: Melatonin has attracted attention because of their high antioxidant
      and anticarcinogenic activity. Otherwise, the use of sunscreens is recommended
      for patients after chemotherapy and radiotherapy treatments or to prevent UV
      radiation-induced skin damages that may result in pre-cancerous and cancerous
      skin lesions. OBJECTIVE: To evaluate the beneficial influence of melatonin in
      topical sunscreen emulsions combined with three common ultraviolet filters.
      METHODS: After the formulation characterization in terms of rheology, stability
      studies were performed. Release studies let us to evaluate its mechanism of
      delivery and ex vivo permeation study through human skin, the amount of melatonin
      retained. The antioxidant activity assay was also carried out, and finally the in
      vivo photoprotective effect in rats was tested as transepidermal water loss and
      erythema formation. RESULTS: The rheological behaviour of formulations was
      pseudoplastic fluid, all emulsions had good physical stability. Release studies
      showed a trend of enhancement in melatonin release from emulsions incorporating
      UV filters and followed a Weibull model. Melatonin permeation was higher from the
      emulsion containing melatonin combined with a mixture of three ultraviolet
      filters (MMIX) formulation. Equally this formulation exhibited the highest
      radical scavenging activity. Finally the photoprotective assay showed that only
      skin areas treated with this formulation were statistically equivalent to the
      unirradiated control area. CONCLUSION: MMIX formulation would be a promising
      formulation for preventing the undesirable adverse effects of UV skin irradiation
      because melatonin not only acts as a potent antioxidant itself, but also is
      capable of activating an endogenous enzymatic protective system against oxidative
      stress.

PMID- 23159283
TI  - Importance of IL-10 and IL-6 during chronic hepatitis C genotype-1 treatment and
      their relation with IL28B.
AB  - This paper investigates serum levels of interleukin 10 (IL-10) and interleukin 6
      (IL-6) in patients with chronic hepatitis C genotype 1 (CHC-GT1), the relation of
      each with clinical and virological characteristics, how they affect the response
      to combined therapy and their relation with the IL28B polymorphisms rs12979860.
      Serum level expression and the polymorphism of IL-10, IL-6 and IL28B were
      determined in 138 CHC-GT1 patients, treated with pegylated interferon/ribavirin
      (pegIFN-alpha/RBV) for 48 weeks, in the following samples: baseline, week-12
      (during treatment) and week-72 (post-treatment). 77 patients (56%) presented
      Sustained Virological Response (SVR) and 61 (44%) were non-SVR. Multivariate
      logistic regression showed that age <= 40 years (aOR=3.7, 95%CI=1.5-8.9,
      P=0.004), low activity of gamma glutamyl transferase (GGT) (aOR=0.9, 95%CI=0.98
      0.99, P=0.028), CC genotype of IL28B polymorphism (aOR=2.7, 95%CI=1.0-7.2,
      P=0.044) and low IL-6 (aOR=0.5, 95%CI=0.3-1.0, P=0.038) were predictor factors of
      virological response. In all patients, following treatment, IL-6 decreased at
      week-12 (P=0.004) from baseline and had returned to basal values at week-72.
      Serum IL-10 concentration was significantly decreased at week-72 only in SVR
      patients (P <= 0.001). When patients were stratified by IL28B polymorphisms
      rs12979860 CC vs non-CC patients, a statistically significant decrease in IL-10
      at week-72 in both groups was observed (P=0.003 and P <= 0.001, respectively).
      None of the polymorphisms of IL-10 or IL-6 studied were associated with SVR.
      CONCLUSIONS: CC genotype of IL28B and low IL-6 serum concentration are factors
      associated independently with SVR. Moreover, decreased IL-10 at week-72 is
      associated with SVR in both CC and non-CC patients, and both factors are
      important to determine the effectiveness of treatment.

PMID- 23159284
TI  - The effect of granulocyte colony stimulating factor receptor gene missense single
      nucleotide polymorphisms on peripheral blood stem cell enrichment.
AB  - Granulocyte-colony stimulating factor (G-CSF) has become the most effective agent
      supporting hematopoietic stem cell transplantation (HSCT). The cognate
      interaction between G-CSF and its specific receptor, G-CSFR, induces the
      mobilization of HSCs and increases their pool in the peripheral blood. G-CSFR has
      a highly conserved structure which may be functionally modulated by the presence
      of missense single nucleotide polymorphisms (SNPs). In this study, we asked
      whether the missense SNPs in G-CSFR could affect the response to G-CSF in HSCT
      patients and donors. Here, for the first time, G-CSFR missense SNPs were screened
      and minor allele frequencies were determined in a specific population with
      Turkish racial background. Five (rs3917991, rs3918001, rs3918018, rs3918019, and
      rs146617729) out of 16 missense SNPs screened were determined with minor allele
      frequencies lower than 0.04. Subsequent association analyses indicated potential
      impact of rs3918001, rs3918018, and rs3918019 minor alleles on peripheral blood
      CD34(+) cell enrichment. Although their frequency is rather low, certain missense
      SNPs, especially which are placed in the conserved regions of G-CSFR may possess
      the capacity to influence the response to G-CSF treatment.

PMID- 23159285
TI  - Bladder cancer and schistosomiasis.
AB  - Schistosoma-associated bladder cancer was believed, for several decades, to be a
      completely unique entity of disease, different from urothelial cancer. This was
      probably due to its distinct clinicopathologic and demographic features that
      varied from those of urothelial entity. The carcinogenesis is an extremely
      complex process resulting from the accumulation of many genetic and epigenetic
      changes leading to alterations in the cell proliferation regulation process. In
      bladder cancer, many of these carcinogenic cascades were not fully documented or
      somewhat conflicting. Inspite of the efforts performed, much is still needed to
      explore the presence or absence of the carcinogenic difference with a different
      etiology. The control of schistosomiasis in certain countries and the subsequent
      decrease in the intensity of infestation showed changing of features approaching
      that of urothelial tumors. However the schistosoma-associated bladder cancer
      presented in more advanced stages than schistosoma-non associated urothelial
      cancer. More recently, data are gathered that, upon applying the same treatment
      protocol and management care, stage by stage comparison of the treatment end
      results were found to be similar in bladder cancer patients with a different
      etiology. All treatment options; including radical cystectomy with or without
      adjuvant or neoadjuvant chemo- or radiotherapy or trimodality bladder preserving
      treatment seem to lead to similar end-results regardless of etiologic factor(s)
      implicated in bladder cancer development.

PMID- 23159286
TI  - Comparative study between the effect of methotrexate and valproic acid on solid
      Ehrlich tumour.
AB  - BACKGROUND: SEC is an undifferentiated tumour used in tumour studies. MTX is an
      antimetabolite used in treatment of cancer, autoimmune diseases and induction of
      abortion. VPA is used as anticonvulsant and is under investigation for treatment
      of cancer. The aim of this work was to compare between the effect of each of MTX
      and VPA on solid Ehrlich tumour in mice. METHODS: Forty albino mice were divided
      into 4 equal groups: control untreated group, SEC group, SEC+MTX group, and
      SEC+VPA group. Tumour volume, tissue CAT, tissue GR, tissue MDA, tissue
      cholesterol and tissue TNF-alpha were determined. A part of the tumour was
      examined for histopathological and immunohistochemical study. RESULTS: MTX alone
      or VPA alone induced a significant increase in tissue CAT and GR with a
      significant decrease in the tumour volume, tissue MDA, cholesterol and TNF-alpha
      and alleviated the histopathological changes with a significant increase in p53
      expression compared to SEC group. This effect was more significant in MTX treated
      group compared to VPA treated group. CONCLUSION: MTX has more antitumour effect
      than VPA against SEC.

PMID- 23159287
TI  - Comparative dosimetric evaluation of three-dimensional conformal and stereotactic
      radiotherapy for treatment of intracranial tumors.
AB  - AIMS: To evaluate the dosimetric profile among three-dimensional conformal
      radiotherapy (3D-CRT) and stereotactic radiotherapy (SRT) for the treatment of
      intracranial tumors. MATERIALS AND METHODS: Seventeen patients with intra cranial
      tumors of benign nature or low malignant potential were enrolled and planned for
      SRT as well as 3D-CRT. Dosimetric comparison between these two plans was done
      considering the following parameters: Target coverage, conformity index, and
      heterogeneity index. RESULTS: The dosimetric parameters of the 3D-CRT plans were
      a little inferior compared with those for the SRT plans. The difference between
      mean target coverage, mean conformity index and mean heterogeneity index for 3D
      CRT and SRT plans was highly significant at P < 0.001 (t = 7.74), P < 0.001 (t =
      5.52), and P < 0.01 (t = 3.15) respectively. CONCLUSION: SRT is a very efficient
      treatment option for intracranial tumors, in view of better target coverage and
      conformality compared with 3D-CRT.

PMID- 23159288
TI  - Potential diagnostic utility of CD56 and claudin-1 in papillary thyroid carcinoma
      and solitary follicular thyroid nodules.
AB  - BACKGROUND AND AIM: The pathological diagnosis of papillary thyroid carcinoma
      (PTC) is usually easily achieved. However distinguishing the follicular variant
      of papillary carcinoma (FVPC) from other follicular thyroid lesions is an area of
      controversy. In this study we investigated the role of CD56 and claudin-1 in
      discriminating the FVPCs from other solitary follicular patterned nodules. We
      also evaluated the application of these two markers in reclassifying the
      controversial cases of the well differentiated tumors of unknown malignant
      potential (WDTs-UMP). MATERIALS AND METHODS: The immunohistochemical expression
      of CD56 and claudin-1 was evaluated in 86 samples of thyroid lesions together
      with 10 samples of normal thyroid tissue. Thyroid lesions included: 29 PTCs
      [classic papillary carcinoma (n = 13) and FVPC (n = 16)], 47 solitary follicular
      patterned nodules [follicular adenomas (n = 12), hyperplastic nodules (n = 32)
      and follicular tumor of unknown malignant potential (n = 3)] and 10 WDTs-UMP.
      RESULTS: The statistical analysis showed significantly different expressions of
      each of CD56 and claudin-1 in the FVPCs versus other solitary follicular
      patterned nodules. Claudin-1 sensitivity (100%) was higher than CD56 sensitivity
      (81.3%). However claudin-1 specificity (80.9%) was < CD56 specificity (89.4%).
      The combined use of CD56 and claudin-1(claudin-1 + /CD56-) showed specificity
      (100%), positive predictive value (100%) and sensitivity (81.3%) in the
      differentiation between the FVPCs and other follicular nodules. In the light of
      this statistical outcome, 5/10 cases of WDTs-UMP expressing the (claudin-1 +
      /CD56-) panel could be rediagnosed as PTC. CONCLUSION: Combined utility of CD56
      and claudin-1 is helpful in diagnosing the FVPC and its differentiation from
      other follicular patterned nodules. Application of these two markers may greatly
      aid in the reevaluation of the WDTs-UMP and interpretation of their expected
      behavior.

PMID- 23159289
TI  - Clinical experience in pediatric neuroblastoma intensity modulated radiotherapy.
AB  - BACKGROUND: In spite of the numerous publications of dosimetric comparison of
      intensity modulated radiotherapy (IMRT) versus conventional radiotherapy in
      pediatrics, few data exist regarding the clinical use of IMRT and its potential
      late effects. PROCEDURE: Pediatric neuroblastoma patients treated between
      November 2008 and October 2010 with IMRT were reviewed. Treatment plans,
      clinical, laboratory and radiological data at the last follow up date were
      evaluated. RESULTS: Thirteen patients received IMRT. The mean age was 4.9 +/- 2
      years. The radiation dose ranged from 21 to 25.5 Gy with a mean dose of 24.06 Gy.
      The mean liver dose was 9.81 Gy. The V8 of the liver was 51 +/- 20%, and the V15
      of the liver was 21 +/- 12%. V18 of the right and left kidneys were 32 +/- 27%
      and 23 +/- 18% respectively. The minimum and maximum vertebral point doses were
      12.82 and 24.87 Gy respectively. The IMRT treatment was well tolerated in terms
      of acute toxicity. At 26 month follow up, second malignancy and skeletal
      asymmetry were not noted, and the liver and the kidney functions showed no
      significant abnormalities. CONCLUSIONS: The use of IMRT in pediatric
      neuroblastoma confers higher target conformality with better sparing of the
      kidneys and it did not show any considerable short term side effects.

PMID- 23159290
TI  - Cardiac resynchronization therapy in patients with chronic heart failure is
      associated with anti-inflammatory and anti-remodeling effects.
AB  - OBJECTIVES: Proinflammatory cytokines, matrix metalloproteinases (MMPs) and their
      tissue inhibitors (TIMPs) play a role in left ventricular (LV) structural
      remodeling. We aimed to investigate the effects of cardiac resynchronization
      therapy (CRT) on serum levels of amino-terminal prohormone B-type natriuretic
      peptide (NT-proBNP), some interleukins (IL-1beta, IL-6, IL-8), MMP-2 and TIMP-2
      in patients with chronic heart failure (CHF). DESIGN AND METHODS: We studied 27
      patients (15 M/12 F) with CHF, III-IV NYHA class, implanted with a biventricular
      pacemaker/defibrillator and 40 healthy subjects (23 M/17 F). Blood samples were
      collected at baseline and 1 week, 3, 6, and 12 months after CRT device
      implantation. Cardiac function was assessed echocardiographically. RESULTS: CRT
      induced significant improvement in the NYHA class (baseline 3.2+/-0.5 vs. 1.0 at
      12 months, P=0.0002) and significant LV reverse remodeling, with a 41% (P=0.001)
      reduction in LV end-systolic volume (LVESV). This was associated with a
      significant reduction in serum NT-proBNP, IL-6 and IL-8. Positive extracellular
      matrix remodeling was illustrated by decreasing levels of MMP-2 and increasing
      TIMP-2. MMP-2/TIMP-2 ratio decreased with 55% (P=0.003) from baseline value at 12
      months and the correlation with LVESV reduction was 0.41 (P=0.001). CONCLUSIONS:
      Structural response to CRT is associated with reduced immune activation and
      positive extracellular matrix remodeling.

PMID- 23159291
TI  - Association of vitamin D with glucose levels in indigenous and mixed population
      Argentinean boys.
AB  - INTRODUCTION: There is little information about low vitamin D concentrations in
      apparently healthy indigenous children in South America. OBJECTIVES: (a) To
      compare the prevalence of hypovitaminosis D in SAC (San Antonio de los Cobres)
      versus BA (Buenos Aires) boys and (b) to determine the association of serum
      vitamin D concentration with age, gender, and risk factors for diabetes. METHODS:
      This cross-sectional study compares 129 boys from SAC with a 98% indigenous
      population, versus 116 boys from BA with a mixed population. Anthropometric
      measures and serum levels of glucose, lipids, insulin, and 25-hydroxyvitamin D
      [25(OH)D] were measured in May 2011 and May 2010 (fall season). Optimal,
      insufficiency, deficiency, and severe deficiency of vitamin D were defined as
      [25(OH)D[levels >=75 nmol/L, 50 to <75 nmol/L, 25 to <50 nmol/L, and <25 nmol/L
      respectively. RESULTS: The mean age was 9.7+/-2.7 in SAC and 11.3+/-2.51 years in
      BA children. Seventeen (13.2%) SAC and 2 (1.7%) BA children were underweight; 99
      (76.7%) SAC and 58 (50.0%) BA children were normal weight; 5 (3.9%) SAC and 15
      (12.9%) BA children were overweight; and 8 (6.2%) SAC and 41 (35.3%) BA children
      were obese (p<0.001). Sixty-six (51.2%) SAC and 1 (0.9%) BA children had vitamin
      D severe deficiency; 58 (45.0%) SAC and 53 (45.7%) BA children had deficiency; 5
      (3.9%) SAC and 61 (52.6%) BA had insufficiency; and 0 (0%) SAC and 1 (0.9%) BA
      children had optimal vitamin D (p<0.001). Therefore, there was a lower prevalence
      of overweight/obesity and a higher prevalence of vitamin D deficiency in SAC than
      in BA children. Separate linear regression models showed an inverse association
      between glucose levels (beta=-0.22; p=0.01) and HOMA=IR (beta=-0.21; p=0.02) with
      vitamin D levels adjusted for age, z-BMI and community. CONCLUSIONS: There was a
      higher prevalence of 25(OH)D deficiency in SAC versus BA boys, suggesting that
      dark skin, high altitudes, or genetic backgrounds could contribute to this
      problem. In addition, we found an inverse association between [25(OH)D] and
      glucose concentration in apparently healthy children. Additional longitudinal
      studies should be done to confirm these findings.

PMID- 23159292
TI  - Proteomic profile in familial breast cancer patients.
AB  - OBJECTIVES: Breast cancer is the most common form of cancer affecting women, and
      the strongest risk factor remains family history. Although screening in
      asymptomatic women seems able to reduce breast-cancer related mortality, it is of
      limited usefulness in young women and patients with familial breast cancer
      syndrome. New diagnostic tools useful for breast cancer management are urgently
      needed. The aim of the present paper is to look for new candidate tumor markers
      useful for diagnosis in these patients. DESIGN AND METHODS: In this prospective
      study 292 serum samples (100 from healthy people, 100 from sporadic breast cancer
      patients and 92 from familial breast cancer patients) were analyzed by SELDI-TOF
      MS. All samples both from cancer patients and healthy subjects were run in
      duplicate and randomly spotted on CM10 and IMAC30 protein chip array. Data were
      analyzed using the expression differential mapping (EDM) tool, decisional tree
      and multivariate analysis. A further in silico investigation was performed in
      order to hypothesize the identity of evidenced peptides. RESULTS: EDM highlighted
      thirteen and sixteen significant differentially expressed peaks by CM10 and
      IMAC30 protein chip respectively. Subsequent analysis showed that two peaks at
      m/z 11730 and 5066 were differentially expressed in sporadic and familial breast
      cancer patients respectively, while a peak at m/z 8127 was overexpressed only in
      familial breast cancer patients. The diagnostic power of protein peaks was tested
      by decisional tree; sensitivity and specificity ranged from 17% to 91.67%.
      CONCLUSIONS: We show that the serum profile of familial breast cancer patients
      was different when compared with that of sporadic breast cancer patients. We
      hypothesized the identity of the most significant peaks, and further studies are
      now planned in order to definitively establish the identity.

PMID- 23159293
TI  - Diagnostic accuracy of soluble urokinase plasminogen activator receptor (suPAR)
      for prediction of bacteremia in patients with systemic inflammatory response
      syndrome.
AB  - OBJECTIVES: Soluble urokinase plasminogen activator receptor (suPAR) serum
      concentrations have recently been described to reflect the severity status of
      systemic inflammation. In this study, the diagnostic accuracy of suPAR, C
      reactive protein (CRP), procalcitonin (PCT), and interleukin-6 (IL-6) to predict
      bacteremia in patients with systemic inflammatory response syndrome (SIRS) was
      compared. METHODS: A total of 132 patients with SIRS were included. In 55
      patients blood cultures had resulted positive (study group 1, Gram positive
      bacteria: Staphylococcus aureus and Streptococcus spp., n=15; study group 2, Gram
      negative bacteria, n=40) and 77 patients had negative blood culture results
      (control group, n=77). Simultaneously with blood cultures suPAR, CRP, PCT, IL-6
      and white blood count (WBC) were determined. RESULTS: SuPAR values were
      significantly higher in study group 1 (median 8.11; IQR 5.78-15.53; p=0.006) and
      study group 2 (median 9.62; IQR 6.52-11.74; p<0.001) when compared with the
      control group (median 5.65; IQR 4.30-7.83). ROC curve analysis revealed an AUC of
      0.726 for suPAR in differentiating SIRS patients with bacteremia from those
      without. The biomarkers PCT and IL-6 showed comparable results. Regarding
      combinations of biomarkers multiplying suPAR, PCT and IL-6 was most promising and
      resulted in an AUC value of 0.804. Initial suPAR serum concentrations were
      significantly higher (p=0.028) in patients who died within 28 days than in those
      who survived. No significant difference was seen for PCT, IL-6 and CRP.
      CONCLUSION: In conclusion, suPAR, IL-6 and PCT may contribute to predicting
      bacteremia in SIRS patients.

PMID- 23159294
TI  - Proteomics in colorectal cancer translational research: biomarker discovery for
      clinical applications.
AB  - Colorectal cancer (CRC) is a major cause of cancer-related death in the western
      world. Screening to detect the disease in an early stage is the most effective
      approach to tackle this problem. In addition, better diagnostic tools for
      assessment of prognosis and prediction of response to drug therapy will allow for
      personalized therapies and better outcomes. Protein biomarkers that reflect tumor
      biology have the potential to address a wide range of clinical needs. These
      include diagnostic (screening) biomarkers for early detection, prognostic
      biomarkers for estimation of disease outcome, predictive biomarkers for adjuvant
      treatment stratification, and surveillance biomarkers for disease monitoring and
      treatment response. An important source for the discovery of potential biomarkers
      comes from mass spectrometry based proteomics research of the biology of CRC
      development. Here, we review recent colon cancer proteomics studies directed at
      identification of biomarker proteins. These include studies that use preclinical
      models (i.e. cell lines or murine tissues) as well as clinical materials (e.g.
      tissue and stool samples). We separately highlight some studies that focused on
      identification of cancer stem cell (CSC) related proteins in tumor spheroids, an
      in vitro model system for investigating CRC treatment response. Recent proteomics
      studies have generated many new candidate protein biomarkers. However, the lack
      of follow-up studies that lead to biomarker verification and/or validation
      remains a limiting factor in the translation of these candidate biomarkers into
      clinical applications. This is partly due to technological limitations which are
      bound to diminish with new technologies, including selected reaction monitoring
      mass spectrometry (SRM-MS). Antibodies are still required, though, both to
      perform high-throughput validation as well as to develop cost-effective tests for
      routine use in a clinical setting.

PMID- 23159295
TI  - Serum carcinoembryonic antigen level is associated with arterial stiffness in
      healthy Korean adult.
AB  - BACKGROUND: Carcinoembryonic antigen (CEA), a widely used tumor marker, has been
      reported to be related with atherosclerosis and cardiovascular disease. However,
      little is known about the relationship between arterial stiffness and CEA level.
      We assessed whether serum CEA level is related with arterial stiffness by
      measuring brachial-ankle pulse wave velocity (ba-PWV) in healthy subjects.
      METHODS: Serum CEA level, ba-PWV and conventional risk factors were measured in
      2909 subjects (1767 men and 1142 women) who underwent routine health checkup. We
      performed correlation, multiple linear regression and multiple logistic
      regression analyses to divide into quartiles according to CEA level. RESULTS: The
      mean values of ba-PWV increased gradually by CEA quartile. After correcting for
      significantly correlated variables, the ba-PWV was independently associated with
      CEA (P<0.001). The odds ratios (95% CI) for high ba-PWV (>75th percentile; men:
      1518 cm/s, women: 1487 cm/s) according to CEA quartile were 1.00 (Q1), 1.044
      (0.659-1.652; Q2), 1.075 (0.688-1.681; Q3), and 1.595 (1.009-2.520; Q4) after
      adjusting for age, blood pressure, BMI, fasting glucose, heart rate, log hs-CRP,
      LDL-cholesterol, WBC count, alcohol intake, smoking and exercise in men
      (P<0.001). The odds ratios (95% CIs) in women were 1.00 (Q1), 1.719 (0.971-3.032;
      Q2), 1.793 (1.019-3.156; Q3), and 2.330 (1.312-4.139; Q4) (P<0.001) after
      adjusting for age, blood pressure, BMI, fasting glucose, heart rate, log hs-CRP,
      lipid profile, uric acid, WBC count, alcohol intake, smoking and exercise.
      CONCLUSIONS: The CEA level is associated with arterial stiffness which measured
      by ba-PWV in healthy Korean men and women.

PMID- 23159297
TI  - Limitations in qualitative point of care hCG tests for detecting early pregnancy.
AB  - BACKGROUND: Detection of early pregnancy in the healthcare setting is important
      for proper patient management. Qualitative point-of-care (POC) human chorionic
      gonadotropin (hCG) testing is often used. There is a gap in the literature for
      evaluating patient samples with low (<300 IU/l) hCG concentration using POC
      devices. METHODS: Specimens (urine, n=289; serum, n=269) with hCG concentrations
      between 2 and >5000 IU/l were evaluated by hCG POC testing. Approximately half of
      these had an hCG concentration<300 IU/l. All specimens were evaluated using the
      OSOM and QuickVue+ POC hCG devices. Pregnancy status was evaluated by patient
      chart review. RESULTS: The OSOM and QuickVue+ devices were able to detect hCG in
      53% (OSOM) and 78% (QuickVue+) of urine samples with an hCG concentration range
      between 20 and 300 IU/l. Serum samples with an hCG concentration range between 10
      and 300 IU/l gave positive results in 79 and 91% of samples tested using the OSOM
      and QuickVue+, respectively. False negative results could not be attributed to
      the high-dose hook effect, the hCG variant effect, or the interpreters'
      evaluation. The mean gestational age for specimens corresponding to the false
      negative results was 4 weeks. CONCLUSIONS: The sensitivity of 2 commonly used hCG
      POC devices is insufficient for detecting very early pregnancy.

PMID- 23159296
TI  - The distribution of apolipoprotein E gene polymorphism in Chinese civil aircrews,
      and a possible risk factor to their overweight and dyslipidemia is cumulative
      flight time.
AB  - BACKGROUND: The prevalence of dyslipidemia and overweight is significantly higher
      in aircrews than that in general population. The purpose of the study was to
      examine the distribution of APOE gene polymorphism and the influence of which as
      well as occupational environment on dyslipidemia and overweight in Chinese civil
      aircrews. METHODS: APOE gene polymorphism was investigated using PCR-RFLP, plasma
      lipid parameters were measured by standard enzymatic kits and personal
      information of the aircrews was collected through questionnaires. RESULTS: The
      allele frequencies among aircrews were epsilon2: 17.0%, epsilon3: 80.9%, and
      epsilon4: 2.1%, APOE gene polymorphism was associated with significant
      differences in TC and LDL-C. E2 individuals had the lowest TC and LDL-C
      concentrations, and E4 participants had the highest levels (p<0.001). In
      addition, the TC and LDL-C concentrations, as well as BMI rose with the
      increasing cumulative flying hours (p<0.05). The further logistic regression
      analysis showed the significant associations of BMI and dyslipidemia (p<0.0001,
      OR=2.093), cumulative flight time and overweight (p<0.0001, OR=1.560).
      CONCLUSIONS: The distribution of APOE alleles among aircrews was provided for the
      first time, which is not fully identical with that among general population.
      These data also suggested the cumulative flight time influenced dyslipidemia and
      overweight as an environmental contributor.

PMID- 23159298
TI  - Measurement of reference intervals for urinary free adrenal steroid levels in
      Japanese newborn infants by using stable isotope dilution gas chromatography/mass
      spectrometry.
AB  - BACKGROUND: In newborn infants, there are no reference intervals for urinary free
      steroids, which are thought to reflect the bioavailable fraction of steroids in
      the blood. We establish a method for simultaneous measurement of urinary free
      adrenal steroids such as pregnenolone, progesterone, 16alpha-hydroxyprogesterone,
      17alpha-hydroxyprogesterone, 21-deoxycortisone, 21-deoxycortisol,
      dehydroepiandrosterone, androstenedione, and 11beta-hydroxyandrostenedione by
      using stable isotope dilution gas chromatography/mass spectrometry (SID-GC/MS)
      and determined the reference intervals for urinary levels of free adrenal
      steroids in Japanese newborn infants. METHODS: Newborn pooled urine was used for
      validation. Spot urine samples were collected from 67 full-term Japanese newborn
      infants (34 male and 33 female infants) at 3-4 days of age to determine reference
      intervals. The extracted and purified free steroids were delivered with
      heptafluorobutyric anhydride and analyzed by SID-GC/MS. RESULTS: We validated a
      SID-GC/MS method with good repeatability and recovery rate. The preliminary
      reference intervals (median [range], MUmol/mol creatinine) were as follows:
      pregnenolone, 4.2 (0.7-31.6); progesterone, 0.5 (not detected (n.d.)-0.6);
      16alpha-hydroxyprogesterone, 1.4 (n.d.-10.3); 17alpha-hydroxyprogesterone, 1.1
      (n.d.-1.9); 21-deoxycortisone, n.d. (n.d.-n.d.); 21-deoxycortisol, n.d. (n.d.
      n.d.); dehydroepiandrosterone, 2.2 (0.6-27.3); androstenedione, 0.7 (n.d.-5.2);
      and 11beta-hydroxyandrostenedione, 2.9 (n.d.-26.7). CONCLUSIONS: We established a
      reliable SID-GC/MS method and were able to determine preliminary reference
      intervals for 9 urinary free adrenal steroids in newborn infants.

PMID- 23159299
TI  - Design and implementation of software for automated quality control and data
      analysis for a complex LC/MS/MS assay for urine opiates and metabolites.
AB  - BACKGROUND: Mass spectrometry provides a powerful platform for performing
      quantitative, multiplexed assays in the clinical laboratory, but at the cost of
      increased complexity of analysis and quality assurance calculations compared to
      other methodologies. METHODS: Here we describe the design and implementation of a
      software application that performs quality control calculations for a complex,
      multiplexed, mass spectrometric analysis of opioids and opioid metabolites.
      RESULTS: The development and implementation of this application improved our data
      analysis and quality assurance processes in several ways. First, use of the
      software significantly improved the procedural consistency for performing quality
      control calculations. Second, it reduced the amount of time technologists spent
      preparing and reviewing the data, saving on average over four hours per run, and
      in some cases improving turnaround time by a day. Third, it provides a mechanism
      for coupling procedural and software changes with the results of each analysis.
      We describe several key details of the implementation including the use of
      version control software and automated unit tests. CONCLUSIONS: These generally
      useful software engineering principles should be considered for any software
      development project in the clinical lab.

PMID- 23159300
TI  - Fibrinolytic system in preeclampsia.
AB  - Preeclampsia (PE) is a multi-system disorder of human pregnancy characterized by
      hypertension and proteinuria. Although its pathogenesis is not fully understood,
      predisposition to endothelial dysfunction is thought to play a crucial part.
      Normotensive pregnancy is associated with increases in coagulation factor levels
      and decreases in natural anticoagulation, leading to a hypercoagulable state.
      This state is thought to be part of a complex physiological adaptation, which
      ensures rapid and effective control of bleeding from the placental site at the
      time of placental separation. In PE, a more pronounced exacerbation of the
      hypercoagulable state is noticed, compared to normotensive pregnancy. Activation
      of coagulation in PE occurs at an early stage of the disease and often antedates
      the clinical symptoms. It is known that PE is associated with fibrin deposition
      in the kidney glomerulus, and in fatal cases, widespread fibrin deposition has
      been a prominent histological finding. Related to the fibrinolytic system in PE,
      the state of the art allows the assumption that blood coagulation overlaps the
      fibrinolytic regulatory mechanism, since fibrin deposition in maternal
      microcirculation is usually found in PE. However, there is still no consensus
      about its specific role. This review aims to discuss the fibrinolytic system in
      PE and its potential implications to the pathogenesis of this disease.

PMID- 23159301
TI  - Dysphagia in a patient with recurrent small-cell lung cancer.

PMID- 23159302
TI  - Effectiveness of a culturally integrated liver cancer education in improving HBV
      knowledge among Asian Americans.
AB  - OBJECTIVE: The aim of this study was to assess the effectiveness of a hepatitis B
      virus (HBV) educational program in increasing HBV knowledge. METHODS: Using a
      cluster randomized control trial to recruit participants from the community-based
      organization in the Baltimore-Washington Metropolitan Area; a total of 877 Asian
      American participants completed a self-administered pretest. HBV knowledge was
      the outcome measure. The intervention group received a 30-minute educational
      program. After the educational program, the intervention group completed a post
      education survey. Six months after the education, all participants were followed
      by phone. RESULTS: The intervention group showed significantly higher knowledge
      scores than the control group at the 6-month follow-up (between-group difference
      was 1.44 for knowledge of transmission modes and 0.59 for sequelae, p < 0.01).
      For the intervention group, the increase in knowledge of HBV transmission modes
      in post-education was much higher than that at the 6-month follow-up (4.18 vs.
      2.07), p < 0.01) compared to baseline. Age was also an important factor on the
      educational effect: Those older than 60 years reported the lowest scores in all
      three points. CONCLUSIONS: Findings suggest that this culturally integrated liver
      cancer educational program increased HBV knowledge. Differential strategies are
      needed to target age groups, separately educating those younger and those older.

PMID- 23159304
TI  - Best worst discrete choice experiments in health: methods and an application.
AB  - A key objective of discrete choice experiments is to obtain sufficient quantity
      of high quality choice data to estimate choice models to be used to explore
      various policy/clinically relevant issues. This paper focuses on a relatively new
      form of choice experiment, 'Best Worst Discrete Choice Experiments' (BWDCEs) and
      their relevance to health research as a new way to meet such an objective. We
      explain what BWDCEs are, how and when to apply them and we present several
      analytical approaches to model the resulting data. We demonstrate this preference
      elicitation approach in an empirical application exploring preferences of 898
      members of the general public in Edmonton and Calgary, Canada for treatment of
      cardiac arrest occurring in a public place and show the gains achieved compared
      to traditional analysis of first best data. We suggest that BWDCEs are a valuable
      way to investigate preferences in the health sector and discuss implications for
      task design, analysis and areas for future research.

PMID- 23159305
TI  - The relationship between organizational culture and performance in acute
      hospitals.
AB  - This paper examines the relationship between senior management team culture and
      organizational performance in English acute hospitals (NHS Trusts) over three
      time periods between 2001/2002 and 2007/2008. We use a validated culture rating
      instrument, the Competing Values Framework, to measure senior management team
      culture. Organizational performance is assessed using a wide range of routinely
      collected indicators. We examine the associations between organizational culture
      and performance using ordered probit and multinomial logit models. We find that
      organizational culture varies across hospitals and over time, and this variation
      is at least in part associated in consistent and predictable ways with a variety
      of organizational characteristics and routine measures of performance. Moreover,
      hospitals are moving towards more competitive culture archetypes which mirror the
      current policy context, though with a stronger blend of cultures. The study
      provides evidence for a relationship between culture and performance in hospital
      settings.

PMID- 23159306
TI  - Health and well-being of movers in rural and urban areas--a grid-based analysis
      of northern Finland birth cohort 1966.
AB  - We examined the association of health and well-being with moving using a detailed
      geographical scale. 7845 men and women born in northern Finland in 1966 were
      surveyed by postal questionnaire in 1997 and linked to 1 km(2) geographical grids
      based on each subject's home address in 1997-2000. Population density was used to
      classify each grid as rural (1-100 inhabitants/km2) or urban (>100
      inhabitants/km2) type. Moving was treated as a three-class response variate (not
      moved; moved to different type of grid; moved to similar type of grid). Moving
      was regressed on five explanatory factors (life satisfaction, self-reported
      health, lifetime morbidity, activity-limiting illness and use of health
      services), adjusting for factors potentially associated with health and moving
      (gender, marital status, having children, housing tenure, education, employment
      status and previous move). The results were expressed as odds ratios (OR) and
      their 95% confidence intervals (CI). Moves from rural to urban grids were
      associated with dissatisfaction with current life (adjusted OR 2.01; 95% CI 1.26
      3.22) and having somatic (OR 1.66; 1.07-2.59) or psychiatric (OR 2.37; 1.21-4.63)
      morbidities, the corresponding ORs for moves from rural to other rural grids
      being 1.71 (0.98-2.98), 1.63 (0.95-2.78) and 2.09 (0.93-4.70), respectively.
      Among urban dwellers, only the frequent use of health services (>= 21 times/year)
      was associated with moving, the adjusted ORs being 1.65 (1.05-2.57) for moves
      from urban to rural grids and 1.30 (1.03-1.64) for urban to other urban grids. We
      conclude that dissatisfaction with life and history of diseases and injuries,
      especially psychiatric morbidity, may increase the propensity to move from rural
      to urbanised environments, while availability of health services may contribute
      to moves within urban areas and also to moves from urban areas to the
      countryside, where high-level health services enable a good quality of life for
      those attracted by the pastoral environment.

PMID- 23159307
TI  - The impact of natural disasters on child health and investments in rural India.
AB  - There is growing concern that climate change will lead to more frequent natural
      disasters that may adversely affect short- and long-term health outcomes in
      developing countries. Prior research has primarily focused on the impact of
      single, large disaster events but very little is known about how small and
      moderate disasters, which are more typical, affect population health. In this
      paper, we present one of the first investigations of the impact of small and
      moderate disasters on childhood morbidity, physical growth, and immunizations by
      combining household data on over 80,000 children from three waves of the Indian
      National Family and Health Survey with an international database of natural
      disasters (EM-DAT). We find that exposure to a natural disaster in the past month
      increases the likelihood of acute illnesses such as diarrhea, fever, and acute
      respiratory illness in children under 5 year by 9-18%. Exposure to a disaster in
      the past year reduces height-for-age and weight-for-age z-scores by 0.12-0.15
      units, increases the likelihood of stunting and underweight by 7%, and reduces
      the likelihood of having full age-appropriate immunization coverage by nearly
      18%. We also find that disasters' effects vary significantly by gender, age, and
      socioeconomic characteristics. Most notably, the adverse effects on growth
      outcomes are much smaller among boys, infants, and families with more
      socioeconomic resources.

PMID- 23159308
TI  - Lack of resveratrol neuroprotection in developing rats treated with kainic acid.
AB  - In adult rats, trans-resveratrol attenuates kainic acid (KA)-induced convulsions
      and the associated hippocampal neurotoxicity. Increased neuronal survival was
      correlated with reduced lipid peroxidation. Since free radical generation after
      KA is age dependent and does not correlate with the onset of seizure-induced
      injury, the present study investigated whether daily trans-resveratrol treatment
      in development could protect the juvenile hippocampus from seizures and onset of
      damage at postnatal (P) day 21. Rat pups were treated with daily injections of
      trans-resveratrol under three dosage regimens (1-15 mg/kg and 20-50mg/kg).
      Weight, electroencephalography (EEG), histology, and N-methyl-d-aspartate (NMDA)
      receptor expression were determined. Malondialdehyde (MDA) concentration was
      assessed from separate animals. trans-Resveratrol did not interfere with growth
      or attenuate KA-induced EEG seizures. However, modest protection was afforded in
      the CA1, the subregion most sensitive to injury at this age. The CA3 and
      entorhinal amygdala cortex (AMG/EC) were not spared. Changes in NR1 subunit or
      NR1 C2 splice variant expression were also not prevented. Baseline MDA
      concentrations of hippocampal subfields were low at P14, P21, and P60 and high in
      aged adults. Glutamate (100 MUM) to stimulate peroxidation products was
      significant at young ages but was much greater at older ages. After KA, elevated
      MDA levels were observed at 24h but only in adult preparations. Thus, while
      antioxidant therapy with trans-resveratrol may be considered as an adjunctive
      therapy to hinder epileptic activity and neurodegeneration at adult ages, it had
      only modest effects at young ages when production of free radicals within limbic
      structures is limited in this experimental model of seizures.

PMID- 23159309
TI  - Pre- and postsynaptic localization of NMDA receptor subunits at hippocampal mossy
      fibre synapses.
AB  - The N-methyl-D-aspartate (NMDA) type of glutamate receptors is involved in
      synaptic plasticity in hippocampal mossy fibre-CA3 pyramidal neuron synapses. The
      ultrastructural localization of NMDA receptor subunits at this synapse type is
      not known. By postembedding electron microscopic immunogold cytochemistry we show
      that the NMDA receptor subunits GluN1, GluN2A, GluN2B, GluN2C and GluN2D are
      located in postsynaptic membranes of mossy fibre as well as CA3 recurrent
      associational commissural synapses. In the mossy fibres the GluN1, GluN2B and
      GluN2D labelling patterns suggested that these subunits were located also
      presynaptically in nerve terminal membranes and in mossy fibre axons. GluN3B was
      predominantly present in mossy fibre synapses as compared to recurrent
      associational commissural synapses, showing a presynaptic labelling pattern. In
      conclusion, while the postsynaptic localization of GluN1, GluN2A, GluN2B, and
      GluN2D is in good agreement with the recent finding of NMDA receptor-dependent
      long term potentiation (LTP) at CA3 mossy fibre synapses, we propose that
      presynaptic GluN1, GluN2B, GluN2D and GluN3B subunits could be involved in
      plastic phenomena such as certain types of LTP and recurrent mossy fibre growth.

PMID- 23159310
TI  - Systemic administration of leptin potentiates the response of neurons in the
      nucleus of the solitary tract to chemoreceptor activation in the rat.
AB  - Leptin microinjections into the nucleus of the solitary tract (NTS) have been
      shown to elicit sympathoexcitatory responses, and potentiate the cardiovascular
      responses to activation of the chemoreflex. In this study, experiments were done
      in Sprague-Dawley rats initially to provide a detailed mapping within the NTS
      complex of cells containing immunoreactivity to the long form of the leptin
      receptor (Ob-Rb). In a second series, this NTS region containing Ob-Rb
      immunoreactive cells was explored for single units antidromically activated by
      stimulation of pressor sites in the rostral ventrolateral medulla (RVLM). These
      antidromically identified neurons were then tested for their response to intra
      carotid injections of leptin (50-100 ng/0.1 ml), and to activation of peripheral
      chemoreceptors following an injection of potassium cyanide (KCN) (80 MUg/0.1 ml)
      into the carotid artery. Cells containing Ob-Rb-like immunoreactivity were found
      predominantly in the caudal NTS: within the medial, commissural and gelatinous
      (sub-postremal area) subnuclei of the NTS complex. Of 73 single units tested in
      these NTS regions, 48 were antidromically activated by stimulation of RVLM
      pressor sites and 25 of these single units responded with an increase in
      discharge rate after intra-carotid injections of leptin. In addition, 17 of these
      leptin responsive neurons were excited by the intra-carotid injections of KCN (80
      MUg/0.1 ml). Furthermore, the excitatory response of these single units to KCN
      was potentiated (59-83%) immediately following the leptin injection. These data
      indicate that leptin responsive neurons in NTS mediate chemoreceptor afferent
      information to pressor sites in the RVLM, and suggest that leptin may act as a
      facilitator on neuronal circuits within the NTS that potentiates the
      sympathoexcitatory responses elicited during the reflex activation of arterial
      chemoreceptors.

PMID- 23159311
TI  - Sharper orientation tuning of the extraclassical suppressive-surround due to a
      neuron's location in the V1 orientation map emerges late in time.
AB  - Neuronal responses in primary visual cortex (V1) can be suppressed by a stimulus
      presented to the extraclassical surround, and such interactions are thought to be
      critical for figure ground segregation and form perception. While surround
      suppression likely originates from both feedforward afferents and multiple
      cortical circuits, it is unclear what role each circuit plays in the surround's
      orientation tuning. To investigate this we recorded from single units in V1 of
      anesthetized cat and analyzed the orientation tuning of the suppressive-surround
      over time. In addition, based on orientation maps derived through optical imaging
      prior to recording, neurons were classified as being located in domains or
      pinwheels. For both types of neurons, shortly after response onset (10 ms) the
      suppressive-surround is broadly tuned to orientation, but this is followed by a
      steep improvement in tuning over the next ~30 ms. While the tuning of the
      pinwheel cells plateaus at this point, tuning is enhanced further for domain
      cells, especially those located superficially in the cortex, reaching a peak at
      80 ms from response onset. This relatively slow evolution of the orientation
      tuning of the suppressive surround suggests that fast-arriving feedforward
      circuits (10 ms) likely only provide broadly tuned suppression, but that feedback
      from higher visual areas which is likely to arrive over the next 30 ms and can
      cover both the receptive field center and the extraclassical surround contributes
      to the initial steep rise in tuning for both cell types. Moreover, we speculate
      that the even later enhancement in tuning for domain neurons could mean the
      involvement of inputs from relatively long-range lateral connections, which not
      only propagate slowly but also link like-oriented domains corresponding to the
      receptive field of only the extraclassical surround.

PMID- 23159312
TI  - A comparative electrographic analysis of the effect of sec-butyl-propylacetamide
      on pharmacoresistant status epilepticus.
AB  - Better treatment of status epilepticus (SE), which typically becomes refractory
      after about 30 min, will require new pharmacotherapies. The effect of sec-butyl
      propylacetamide (SPD), an amide derivative of valproic acid (VPA), on
      electrographic status epilepticus (ESE) was compared quantitatively to other
      standard-of-care compounds. Cortical electroencephalograms (EEGs) were recorded
      from rats during ESE induced with lithium-pilocarpine. Using a previously
      published algorithm, the effects of SPD on ESE were compared quantitatively to
      other relevant compounds. To confirm benzodiazepine resistance, diazepam (DZP)
      was shown to suppress ESE when administered 15 min after the first motor seizure,
      but not after 30 min (100mg/kg). VPA (300 mg/kg) also lacked efficacy at 30 min.
      SPD (130 mg/kg) strongly suppressed ESE at 30 min, less after 45 min, and not at
      60 min. At a higher dose (180 mg/kg), SPD profoundly suppressed ESE at 60 min,
      similar to propofol (100mg/kg) and pentobarbital (30 mg/kg). After 4-6h of SPD
      induced suppression, EEG activity often overshot control levels at 7-12h.
      Valnoctamide (VCD, 180 mg/kg), an SPD homolog, was also efficacious at 30 min.
      SPD blocks pilocarpine-induced electrographic seizures when administered at 1h
      after the first motor seizure. SPD has a faster onset and greater efficacy than
      DZP and VPA, and is similar to propofol and pentobarbital. SPD and structurally
      similar compounds may be useful for the treatment of refractory ESE. Further
      development and use of automated analyses of ESE may facilitate drug discovery
      for refractory SE.

PMID- 23159313
TI  - Stanniocalcin 1 is important for poststroke functionality, but dispensable for
      ischemic tolerance.
AB  - Stanniocalcin 1 (STC1), originally described as an antihypercalcemic hormone in
      fish, is highly expressed in differentiated mammalian neurons. Mild hypoxic
      treatment and focal cerebral ischemia induce upregulation of STC1 in the brain.
      These findings prompted us to investigate whether STC1 contributes to
      neuroprotection after ischemia and whether STC1 is required for development of
      ischemic tolerance. We induced 60 minutes of temporary middle cerebral artery
      occlusion in wild type (WT) and STC1-deficient mice (STC1(-/-)) with or without
      prior hypoxic preconditioning (HPC, 8% oxygen for 6 hours followed by
      reoxygenation for 24 hours). Infarct sizes, neurological scores, and Stc1, Stc2,
      and Il-6 mRNA brain levels were measured 24 hours after ischemia. Additionally,
      we examined blood-brain barrier (BBB) integrity (Evans Blue fluorescence) under
      normal conditions and 0 and 24 hours after hypoxia. STC1(-/-) and WT mice
      developed brain infarcts of similar size. In both strains, HPC triggered ischemic
      tolerance with similar reduction in infarct size. However, STC1(-/-) mice had
      worse neurological scores in both scenarios. HPC induced upregulation of STC1 and
      STC2 in WT mice and of STC2 in STC1(-/-) mice. Ischemic STC1(-/-) mice showed
      significantly lower Il-6 mRNA expression than ischemic WT mice. Evans Blue
      fluorescence levels showed no difference in between WT and STC1(-/-) mice under
      evaluated conditions, thus BBB integrity is preserved despite STC1 deficiency.
      STC1 was not crucial for the development of ischemic tolerance triggered by HPC
      or for preserving BBB integrity but may be involved in functional recovery after
      stroke.

PMID- 23159314
TI  - Anti-inflammatory properties rather than anti-oxidant capability is the major
      mechanism of neuroprotection by sodium salicylate in a chronic rotenone model of
      Parkinson's disease.
AB  - Parkinson's disease (PD) is the second most common neurodegenerative disorder
      manifesting in motor, cognitive and behavioral anomalies. Loss of dopaminergic
      neurons in the substantia nigra region of the brain is the hallmark feature of
      PD, which is attributed to oxidative and inflammatory stress besides other
      diverse factors and hence drugs targeting these pathways hold promise as neuro
      therapeutics. The anti-oxidative as well as anti-inflammatory properties of
      sodium salicylate (SS), suggest its neuroprotective potentials in PD. Since PD is
      a progressive neurodegenerative disorder, the mechanistic basis for utilizing SS
      as a neuroprotectant in PD could be better understood in the chronic models. The
      present study utilizes a rotenone-based model of PD to evaluate the neuro
      modulatory efficacy of SS. Subcutaneous injection of rotenone (2mg/kg body
      weight) was given to male SD rats every day, for a period of 5 weeks, which
      developed all the essential features of PD in these animals. Simultaneously,
      another group was injected SS intraperitoneally at the dose of 100mg/kg body
      weight, in addition to the rotenone. In the animals receiving rotenone+SS,
      significant improvement was observed in the various characteristic hallmarks of
      PD such as dopamine and tyrosine hydroxylase levels as well as the motor
      dysfunction symptoms. It attenuated the reactive oxygen species levels
      significantly but failed to reduce the levels of protein carbonylation and lipid
      peroxidation. However, SS effectively abridged the levels of inflammatory
      mediators like cyclooxygenase-2 (COX-2), nuclear factor kappa B and inducible
      nitric oxide synthase. Correspondingly, a significant decrease in the levels of
      pro-inflammatory cytokines interleukin-6, interleukin-1beta and tumor necrosis
      factor-alpha was also observed following SS co-treatment. Thus, neuroprotective
      efficacy of SS in this chronic model of PD can be largely attributed to its anti
      inflammatory effects rather than its free radical-scavenging properties.

PMID- 23159315
TI  - Failure of axonal transport induces a spatially coincident increase in astrocyte
      BDNF prior to synapse loss in a central target.
AB  - Failure of anterograde transport to distal targets in the brain is a common
      feature of neurodegenerative diseases. We have demonstrated in rodent models of
      glaucoma, the most common optic neuropathy, early loss of anterograde transport
      along the retinal ganglion cell (RGC) projection to the superior colliculus (SC)
      is retinotopic and followed by a period of persistence of RGC axon terminals and
      synapses through unknown molecular pathways. Here we use the DBA/2J mouse model
      of hereditary glaucoma and an acute rat model to demonstrate that retinotopically
      focal transport deficits in the SC are accompanied by a spatially coincident
      increase in brain-derived neurotrophic factor (BDNF), especially in hypertrophic
      astrocytes. These neurochemical changes occur prior to loss of RGC synapses in
      the DBA/2J SC. In contrast to BDNF protein, levels of Bdnf mRNA decreased with
      transport failure, even as mRNA encoding synaptic structures remained unchanged.
      In situ hybridization signal for Bdnf mRNA was the strongest in SC neurons, and
      labeling for the immature precursor pro-BDNF was very limited. Subcellular
      fractionation of SC indicated that membrane-bound BDNF decreased with age in the
      DBA/2J, while BDNF released from vesicles remained high. These results suggest
      that in response to diminished axonal function, activated astrocytes in the brain
      may sequester mature BDNF released from target neurons to counter stressors that
      otherwise would challenge survival of projection synapses.

PMID- 23159316
TI  - Alpha4beta2 and alpha7 nicotinic acetylcholine receptor binding predicts choice
      preference in two cost benefit decision-making tasks.
AB  - Nicotinic receptors have been linked to a wide range of cognitive and behavioral
      functions, but surprisingly little is known about their involvement in cost
      benefit decision making. The goal of these experiments was to determine how
      nicotinic acetylcholine receptor (nAChR) expression is related to two forms of
      cost benefit decision making. Male Long Evans rats were tested in probability-
      and delay-discounting tasks, which required discrete trial choices between a
      small reward and a large reward associated with varying probabilities of omission
      and varying delays to reward delivery, respectively. Following testing,
      radioligand binding to alpha4beta2 and alpha7 nAChR subtypes in brain regions
      implicated in cost benefit decision making was examined. Significant linear
      relationships were observed between choice of the large delayed reward in the
      delay discounting task and alpha4beta2 receptor binding in both the dorsal and
      ventral hippocampus. Additionally, trends were found suggesting that choice of
      the large costly reward in both discounting tasks was inversely related to
      alpha4beta2 receptor binding in the medial prefrontal cortex and nucleus
      accumbens shell. Similar trends suggested that choice of the large delayed reward
      in the delay discounting task was inversely related to alpha4beta2 receptor
      binding in the orbitofrontal cortex, nucleus accumbens core, and basolateral
      amygdala, as well as to alpha7 receptor binding in the basolateral amygdala.
      These data suggest that nAChRs (particularly alpha4beta2) play both unique and
      common roles in decisions that require consideration of different types of reward
      costs.

PMID- 23159318
TI  - Identification in the rat brain of a set of nuclear proteins interacting with H1
      degrees  mRNA.
AB  - Synthesis of H1 degrees  histone, in the developing rat brain, is also regulated
      at post-transcriptional level. Regulation of RNA metabolism depends on a series
      of RNA-binding proteins (RBPs); therefore, we searched for H1 degrees  mRNA
      interacting proteins. With this aim, we used in vitro transcribed, biotinylated
      H1 degrees  RNA as bait to isolate, by a chromatographic approach, proteins which
      interact with this mRNA, in the nuclei of brain cells. Abundant RBPs, such as
      heterogeneous nuclear ribonucleoprotein (hnRNP) K and hnRNP A1, and molecular
      chaperones (heat shock cognate 70, Hsc70) were identified by mass spectrometry.
      Western blot analysis also revealed the presence of cold shock domain-containing
      protein 2 (CSD-C2, also known as PIPPin), a brain-enriched RBP previously
      described in our laboratory. Co-immunoprecipitation assays were performed to
      investigate the possibility that identified proteins interact with each other and
      with other nuclear proteins. We found that hnRNP K interacts with both hnRNP A1
      and Hsc70 whereas there is no interaction between hnRNP A1 and Hsc70. Moreover,
      CSD-C2 interacts with hnRNP A1, Y box-binding protein 1 (YB-1), and hnRNP K. We
      also have indications that CSD-C2 interacts with Hsc70. Overall, we have
      contributed to the molecular characterization of a ribonucleoprotein particle
      possibly controlling H1 degrees  histone expression in the brain.

PMID- 23159317
TI  - Cervical spinal demyelination with ethidium bromide impairs respiratory (phrenic)
      activity and forelimb motor behavior in rats.
AB  - Although respiratory complications are a major cause of morbidity/mortality in
      many neural injuries or diseases, little is known concerning mechanisms whereby
      deficient myelin impairs breathing, or how patients compensate for such changes.
      Here, we tested the hypothesis that respiratory and forelimb motor functions are
      impaired in a rat model of focal dorsolateral spinal demyelination (ethidium
      bromide, EB). Ventilation, phrenic nerve activity and horizontal ladder walking
      were performed 7-14 days post-C2 injection of EB or vehicle (SHAM). EB caused
      dorsolateral demyelination at C2-C3 followed by significant spontaneous
      remyelination at 14 days post-EB. Although ventilation did not differ between
      groups, ipsilateral integrated phrenic nerve burst amplitude was significantly
      reduced versus SHAM during chemoreceptor activation at 7 days post-EB but
      recovered by 14 days. The ratio of ipsi- to contralateral phrenic nerve amplitude
      correlated with cross-sectional lesion area. This ratio was significantly reduced
      7 days post-EB versus SHAM during baseline conditions, and versus SHAM and 14-day
      groups during chemoreceptor activation. Limb function ipsilateral to EB was
      impaired 7 days post-EB and partially recovered by 14 days post-EB. EB provides a
      reversible model of focal, spinal demyelination, and may be a useful model to
      study mechanisms of functional impairment and recovery via motor plasticity, or
      the efficacy of new therapeutic interventions to reduce severity or duration of
      disease.

PMID- 23159319
TI  - D-cycloserine administered directly to infralimbic medial prefrontal cortex
      enhances extinction memory in sucrose-seeking animals.
AB  - d-Cycloserine (DCS), a co-agonist at the N-methyl-D-aspartate (NMDA) receptor,
      has proven to be an effective adjunct to cognitive behavioral therapies that
      utilize extinction. This pharmacological-based enhancement of extinction memory
      has been primarily demonstrated in neuropsychiatric disorders characterized by
      pathological fear (e.g. posttraumatic stress disorder and various phobias). More
      recently, there has been an interest in applying such a strategy in the disorders
      of appetitive learning (e.g. substance abuse and other addictions), but these
      studies have generated mixed results. Here we first examined whether extinction
      memory encoding in a sucrose self-administration model is dependent on NMDA
      receptors. The NMDA antagonist (+/-)-3-(2-carboxypiperazin-4-yl)propyl-1
      phosphonic acid (5mg/kg, i.p.) administered 2h prior to the first extinction
      training session effectively inhibited extinction memory recall 24h later,
      without affecting the expression of the conditioned sucrose-seeking response
      while the drug was on board. This profile of effects suggests a specific effect
      on extinction memory consolidation. Next, we sought to enhance extinction memory
      using the co-agonist DCS (10 MUg/side) by infusion directly into infralimbic
      medial prefrontal cortex, a brain site implicated in extinction memory recall in
      conditioned fear models. Indeed, infusion of DCS immediately after the first
      extinction training session effectively enhanced extinction memory recall 24h
      later. Collectively, these data suggest that the neurobiological mechanisms and
      the neurocircuitry mediating extinction memory are similar regardless of the
      valence (aversive or appetitive) of the conditioned behavior, and that similar
      pharmacological strategies for treatment may be applied to neuropsychiatric
      disorders characterized by a failure to inhibit pathological emotional memories.

PMID- 23159320
TI  - Striatal dopamine D1 receptors are involved in the dissociation of learning based
      on reward-magnitude.
AB  - Here we investigate the contribution of striatal dopamine receptors (D1) to the
      influence of reward-magnitude on learning. Pigeons (Columba livia) were trained
      on a discrimination-task with two pairs of stimuli; correct discrimination
      resulted in a large reward in one pair of stimuli and in a small reward in the
      other pair. Acquisition of the discrimination-task was accompanied by
      intracranial injections to the medial striatum, either of a dopamine-antagonist
      (Sch23390) or of vehicle. In the control-condition the rate of learning was
      modulated by the magnitude of the reward; discrimination was learned faster if
      contingent rewards were large and learning was slower if contingent rewards were
      small. Following injections of D1 antagonist this effect vanished even though the
      ability to discriminate between the rewards was unaffected. Interestingly, the
      mean rate of learning was indistinguishable between the control and antagonist
      conditions. Consequently, it appears that not learning per se but the effect of
      reward-magnitude on learning is mediated through D1 receptors in the striatum. We
      argue that the injections of dopamine-antagonist cause a shift in strategy
      underlying learning. In the control-condition animals rely on positive feedback
      and thus learning is affected by the magnitude of the contingent reward; in the
      antagonist-condition, however, learning might rely on negative feedback and is
      thus insensitive to reward-magnitude.

PMID- 23159321
TI  - Future of pediatric tonsillectomy and perioperative outcomes.
AB  - OBJECTIVE: Although commonly performed, pediatric tonsillectomy is not
      necessarily a low risk procedure due to potentially life threatening
      perioperative complications. There is paucity of literature on lethal anesthesia
      and surgical complications of tonsillectomy. In this article, we have reviewed
      both minor and serious complications following tonsillectomy. Hemorrhage, burn
      injuries, respiratory complications, postoperative nausea and vomiting, and pain
      management are discussed. We have highlighted our practice of pain management at
      Cincinnati Children's Hospital after tonsillectomy recent warning about codeine
      by the FDA on children undergoing tonsillectomy. We describe post-tonsillectomy
      outcomes including postanesthesia care unit stay, post discharge maladaptive
      behavioral outcomes and finally effective ways to identify children at risk for
      anesthesia and a few preventive strategies. METHODS: In addition to literature
      review, the LexisNexis "MEGATM Jury Verdicts and Settlements" database was
      reviewed from 1984 through 2010 for deaths and complications during and following
      tonsillectomy. Data including year of case, cause of death, surgical, anesthetic
      and postoperative opioid related complications, injury, case result, and judgment
      awarded were collected and analyzed. RESULTS: The results of this analysis are
      presented with an emphasis on hemorrhage and on anesthesia and opioid related
      claims and their characteristics. Two hundred and thirty-three claim reports were
      reviewed. There were 96 deaths (41%) and 137 perioperative injuries (59%). Deaths
      were primarily related to surgery (n=46, 48%) with post-tonsillectomy bleed the
      most frequent cause (n=38, 40%) followed by opioid toxicity (n=17, 18%) and
      anesthesia complications (n=9, 9%). Non-fatal injuries included, postoperative
      bleeding (n=59, 25%), impaired function (n=29, 12%), anoxic events (n=20, 9%) and
      postoperative opioid toxicity (n=20, 8.6%). Anoxic event was noted to have the
      highest monetary award with a mean award at $9,017,379. Injuries (including
      anoxia) had higher mean monetary awards than deaths. CONCLUSION: Tonsillectomy in
      children carries a high risk of perioperative complications and malpractice
      claims. Though postoperative bleeding is the most common complication associated
      with malpractice claims, anoxia related to anesthesia and opioids had the
      greatest overall risk from a monetary standpoint.

PMID- 23159322
TI  - Fractal analysis for quantification of grazing paths of cows on homogeneous
      pastures.
AB  - Fractal analysis was applied to grazing paths in non-patchy environments to
      clarify the behavioral information available from the analysis and to evaluate
      the effect of social factors on grazing paths. The grazing paths of Holstein
      Friesian cows in groups of 4 (GROUP-4) and 10 cows (GROUP-10) on a spatially
      homogeneous pasture were observed. Application of fractal analysis could quantify
      three aspects of grazing paths of cows: (1) hierarchical scales, (2) structure
      and (3) sinuosity by scale. In this study, regardless of the group size, the
      hierarchical scale of grazing paths was approximately 10 m. The paths showed
      different patterns below and above the 10 m scale. For both group sizes, fractal
      dimension (an index of sinuosity) below the 10 m scale was smaller than fractal
      dimension above 10 m scale suggesting that the paths below the 10 m scale were
      straighter than that above the 10 m scale. The fractal dimensions below and above
      the 10 m scale were significantly larger for GROUP-4 than for GROUP-10 (P<0.05).
      Sinuosity of paths of GROUP-4 was higher than that of GROUP-10 over the entire
      scale. From these three aspects, fractal analysis can clarify the factors related
      to grazing paths of herbivores.

PMID- 23159323
TI  - Examining the temporal relationships between childhood obesity and asthma.
AB  - Childhood obesity has become an issue of increasing concern to health researchers
      and policymakers in the United States. One important chronic health condition
      linked to obesity is pediatric asthma. Although researchers have speculated that
      both conditions may have common origins, the majority of research in this area
      has focused on a unidirectional relationship between obesity and later asthma.
      However, much of the literature is limited by its reliance on cross-sectional
      data and its failure to examine the possibility that asthma may influence weight
      fluctuations through changes in physical and sedentary activity. Using data from
      the Early Childhood Longitudinal Study-Kindergarten Cohort (ECLS-K), I explore
      the bidirectional relationships between childhood obesity and asthma. The results
      in this paper suggest that past asthma levels are positively correlated with
      changes in BMI and the onset of obesity. However, only new onset asthma is
      positively correlated with subsequent changes in BMI. The potential mechanisms
      are unclear, as I find little evidence that asthma is structurally related to
      changes in physical or sedentary activity over time. When testing the prevailing
      hypothesis that obesity is related to subsequent asthma, I find that lagged
      weight status is strongly related to asthma prevalence levels but that the onset
      of overweight or obesity is not associated with the subsequent onset of asthma.
      These results suggest that the onset of asthma may be related to subsequent
      weight gain over time. 

PMID- 23159324
TI  - Apoptosis phenomenon in the schistosomulum and adult worm life cycle stages of
      Schistosoma japonicum.
AB  - Apoptosis is an important aspect of a number of biological processes, from
      embryogenesis to the stress-injury response. It plays a central role in balancing
      cell proliferation and tissue remodeling activity in many organisms. In the
      present study, apoptosis in 14 days post infection schistosomula was evaluated
      using TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick-end
      labeling) assays and DAPI staining. Additionally, flow cytometry using the
      Annexin V-FITC/propidium iodide (PI) (Annexin V/PI) assay confirmed the
      percentage of early apoptotic, late apoptotic, and necrotic cells in 14 and 23
      days post infection worms. Conserved Domain Database (CDD) BLAST analysis and
      alignment analysis of known schistosome proteins demonstrated the feasibility of
      detecting the activity of caspase-3 and -7 using the caspase-3/7 Glo analysis
      assay. Analysis of caspase-3 and -7 activities in schistosome demonstrated that
      both caspases were active in each developmental stage of Schistosoma japonicum,
      but was highest in the 14 days post infection schistosomula. Additionally, the
      caspase peptide inhibitor (Z-VAD-FMK) inhibited the caspase-3/7 activity at all
      developmental stages examined. Therefore, we hypothesized that two main signaling
      pathways are involved in apoptosis in S. japonicum, the caspase cascade and the
      mitochondrial-initiated pathway. We have constructed a model of these two
      pathways, including how they may interact and their biological outcomes. qRT-PCR
      analyses of the gene expression profiles of apoptosis-related genes supported our
      hypothesis of the relationship between the apoptotic pathway and parasite
      development. The data presented here demonstrates that apoptosis is an important
      biological process for the survival and development of the schistosome, and
      identifies potential novel therapeutic targets.

PMID- 23159325
TI  - Cloning and characterization of a fish specific gelsolin family gene, ScinL, in
      olive flounder (Paralichthys olivaceus).
AB  - Scinderin like (ScinL) gene is a unique gelsolin family gene found only in fish.
      In this study ScinL gene was cloned in olive flounder for the first time and
      characterized its expression and function. Flounder ScinL cDNA consists of 2911
      nucleotides encoding a putative protein of 720 amino acids (79.4 kDa). In
      phylogenetic analysis, flounder ScinL is closely related to ScinL of zebra fish,
      anableps, and fugu with the similarity of 51-72%. Fish ScinLs are positioned
      between gelsolin and scinderin of other species. Flounder ScinL protein has the
      highly conserved actin and PIP2 binding sites, Ca(2+) coordination site, and a C
      terminal latch helix preventing the activation of ScinL protein in the absence of
      Ca(2+). Putative binding sites for NFAT and AP-1 were found in 5' flanking
      region. Constitutive ScinL expression was found in most organs and the expression
      level was higher in gill, head kidney, trunk kidney, spleen and skin than muscle,
      stomach, intestine and brain. In Q-PCR analysis ScinL and CYP1A1 gene expression
      were significantly upregulated by BaP in head kidney in vivo and in vitro, and in
      macrophage cells. Upregulated ScinL expression by BaP was blocked by EGTA,
      indicating a calcium dependent regulation of ScinL expression.

PMID- 23159326
TI  - The development of central venous access device flushing guidelines utilizing an
      evidence-based practice process.

PMID- 23159327
TI  - Sibling relationship quality and psychopathology of children and adolescents: a
      meta-analysis.
AB  - In the current meta-analysis, we investigated the link between child and
      adolescent sibling relationship quality (warmth, conflict and differential
      treatment) and internalizing and externalizing problems, and potential moderators
      of these associations. From 34 studies, we obtained 85 effect sizes, based on
      12,257 children and adolescents. Results showed that more sibling warmth, less
      sibling conflict and less differential treatment were all significantly
      associated with less internalizing and externalizing problems. Effect sizes for
      sibling conflict were stronger than for sibling warmth and differential
      treatment, and associations for internalizing and externalizing problems were
      similar in strength. Effect sizes were moderated by sibling gender combination
      (stronger effects for higher percentage brother pairs), age difference between
      siblings (stronger effects for smaller age differences), and developmental period
      (stronger effect sizes for children than for adolescents). These results indicate
      that the sibling context is important when considering psychopathology. In
      addition to the overwhelming evidence of the impact of parent-child and marital
      relationships on child and adolescent development, the present meta-analysis is a
      reminder that the sibling relationship warrants more attention in research as
      well as in clinical settings.

PMID- 23159328
TI  - Conditional risk for PTSD among Latinos: a systematic review of racial/ethnic
      differences and sociocultural explanations.
AB  - Conditional risk for Posttraumatic Stress Disorder (PTSD)--defined as prevalence,
      onset, persistence, or severity of PTSD after traumatic exposure--appears to be
      higher among Latinos relative to non-Latinos after accounting for
      sociodemographic factors. This systematic review focuses on differences in
      conditional risk for PTSD between Latinos and non-Latinos (White, Black, or
      combined) and across Latino subgroups in studies that adjust for trauma exposure.
      We discuss methodological characteristics of existing articles and sociocultural
      explanatory factors. Electronic bibliographic searches were conducted for English
      language articles published in peer-reviewed journals between 1991 and 2012. We
      followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses
      guidelines. Twenty-eight articles met inclusion criteria. Consistent support was
      found for elevated rates of PTSD onset and PTSD severity among Latinos relative
      to non-Latino Whites. The evidence on racial/ethnic differences in conditional
      risk for PTSD prevalence and PTSD persistence is mixed. Twenty-four articles
      evaluated sociocultural explanations, with the strongest support found for
      racial/ethnic variation in peri-traumatic responses and structure of PTSD. There
      were also consistent main effects for social disadvantage in studies that
      simultaneously adjusted for effects of race/ethnicity. Future research should use
      theoretically-driven models to formally test for interactions between
      sociocultural factors, race/ethnicity, and PTSD probability.

PMID- 23159329
TI  - Distinct roles of methamphetamine in modulating spatial memory consolidation,
      retrieval, reconsolidation and the accompanying changes of ERK and CREB
      activation in hippocampus and prefrontal cortex.
AB  - Drugs of abuse modulated learning and memory in humans yet the underlying
      mechanism remained unclear. The extracellular signal-regulated kinase (ERK) and
      the transcription factor cAMP response element-binding protein (CREB) were
      involved in neuroplastic changes associated with learning and memory. In the
      current study, we used a Morris water maze to examine the effect of
      methamphetamine (METH) on different processes of spatial memory in mice. We then
      investigated the status of ERK and CREB in the hippocampus and prefrontal cortex
      (PFC). We found that 1.0 mg/kg dose of METH facilitated spatial memory
      consolidation when it was injected immediately after the last learning trial. In
      contrast, the same dose of METH had no effect on spatial memory retrieval when it
      was injected 30 min before the test. Furthermore, 1.0 mg/kg dose of METH injected
      immediately after retrieval had no effect on spatial memory reconsolidation.
      Activation of both ERK and CREB in the hippocampus was found following memory
      consolidation but not after retrieval or reconsolidation in METH-treated mouse
      groups. In contrast, activation of both ERK and CREB in the PFC was found
      following memory retrieval but not other processes in METH-treated mouse groups.
      These results suggested that METH facilitated spatial memory consolidation but
      not retrieval or reconsolidation. Moreover, activation of the ERK and CREB
      signaling pathway in the hippocampus might be involved in METH-induced spatial
      memory changes.

PMID- 23159330
TI  - Behavioural and EEG effects of chronic rapamycin treatment in a mouse model of
      tuberous sclerosis complex.
AB  - Tuberous Sclerosis Complex (TSC) is a multisystem genetic disorder caused by
      mutation in either Tsc1 or Tsc2 genes that leads to the hyper activation of the
      mTOR pathway, a key signalling pathway for synaptic plasticity. TSC is
      characterized by benign tumors arising in different organs and severe
      neuropsychiatric symptoms, such as epilepsy, intellectual disability, autism,
      anxiety and depressive behaviour. Rapamycin is a potent inhibitor of mTOR and its
      efficacy in treating epilepsy and neurological symptoms remains elusive. In a
      mouse model in which Tsc1 has been deleted in embryonic telencephalic neural stem
      cells, we analyzed anxiety- and depression-like behaviour by elevated-plus maze
      (EPM), open-field test (OFT), forced-swim test (FST) and tail-suspension test
      (TST), after chronic administration of rapamycin. In addition, spectral analysis
      of background EEG was performed. Rapamycin-treated mutant mice displayed a
      reduction in anxiety- and depression-like phenotype, as shown by the EPM/OFT and
      FST, respectively. These results were inline with EEG power spectra outcomes. The
      same effects of rapamycin were observed in wild-type mice. Notably, in
      heterozygous animals we did not observe any EEG and/or behavioural variation
      after rapamycin treatment. Together these results suggest that both TSC1 deletion
      and chronic rapamycin treatment might have a role in modulating behaviour and
      brain activity, and point out to the potential usefulness of background EEG
      analysis in tracking brain dysfunction in parallel with behavioural testing.

PMID- 23159331
TI  - Perseverative behavior in rats with methamphetamine-induced neurotoxicity.
AB  - Methamphetamine induces monoamine depletions thought to contribute to cognitive
      and behavioral dysfunctions. Previously, we reported that methamphetamine-induced
      neurotoxicity is associated with impaired formation of stimulus-response
      associations. Additionally, subjective observations suggested that behavioral
      flexibility might be affected. Thus, the present study examined whether
      methamphetamine neurotoxicity induces perseverative behavior. Rats were
      pretreated with (+/-)-methamphetamine (4 * 10 mg/kg, 2-hr intervals) or saline.
      Three weeks later, rats were trained to press a lever on one side of an operant
      chamber and then retrieve the reinforcer from a magazine on the opposite side
      until they reached criterion (>50 reinforcers/30-min). After four consecutive
      sessions performing the task at criterion, rats were sacrificed and brains
      removed for monoamine determinations. Methamphetamine-pretreated rats had ~50%
      loss of striatal dopamine and prefrontal serotonin. Methamphetamine- and saline
      pretreated rats were not different in the number of sessions required to reach
      criterion or in the total numbers of lever presses and/or head entries made
      across the four consecutive sessions at criterion-level performance. However,
      methamphetamine-pretreated rats earned fewer reinforcers, because they made extra
      lever-presses and head entries when they should have been retrieving the
      reinforcer or returning to the lever. Latencies for methamphetamine-pretreated
      rats to switch between the two behaviors also were significantly slower than
      latencies for controls. Interestingly, the degree of additional lever-presses
      negatively correlated with serotonin-transporter binding in the prefrontal
      cortex, even in saline-pretreated controls. These data suggest that
      methamphetamine-induced partial monoamine toxicity is associated with
      perseveration and that the degree of perseveration may depend on serotonin
      innervation of the frontal cortex.

PMID- 23159332
TI  - Delayed presentation of perisplenic abscess following arterial embolization.
AB  - INTRODUCTION: Splenic abscess formation is a rare but significant complication
      that may occur after non-operative management (NOM) of a blunt splenic injury
      (BSI). we describe an unusual case of perisplenic abscess formation nearly 4
      months after splenic artery angioembolization for a grade III splenic laceration.
      PRESENTATION OF CASE: A 52-year-old male was transferred to the Emergency
      Department (ED) of our institution after falling off his bicycle. He was
      hemodynamically stable but complained of left upper quadrant pain. Computed
      tomography (CT) was notable for a Grade III splenic laceration. The patient
      underwent a successful splenic artery embolization on hospital day 1. He had an
      uneventful post-embolization course and was discharged 3 days later, afebrile,
      with a stable hematocrit. Four months after his initial presentation, the patient
      presented to the ED with fever, malaise, and left upper quadrant abdominal pain.
      A CT scan revealed a multiloculated perisplenic abscess. He underwent a
      splenectomy and drainage of peri-splenic abscess, received a course of
      antibiotics, and had an uneventful recovery. DISCUSSION: NOM including splenic
      angioembolization (SAE) is the standard of care for blunt splenic trauma in
      hemodynamically stable patients. Known complications from SAE include bleeding,
      missed injuries to the diaphragm and pancreas, and splenic abscess. This report
      documents a delayed perisplenic abscess following NOM of blunt splenic trauma, a
      rare but potential complication of SAE. CONCLUSION: Formation of a perisplenic
      abscess may occur several months after NOM of a blunt splenic injury. Prompt
      surgical management and antibiotic therapy are critical to avoid life-threatening
      complications.

PMID- 23159333
TI  - Role of cortical reorganization on the effect of 5-HT pharmacotherapy for spinal
      cord injury.
AB  - Cortical reorganization or expansion of the intact cortical regions into the
      deafferented cortex after complete spinal transection in neonatally spinalized
      rats was shown to be essential for increases in weight-supported stepping at
      adulthood. The novel somatotopic organization identified in these animals can be
      induced by exercise or spinal transplants that bridge the site of injury.
      However, the role of cortical reorganization in increased weight-supported (WS)
      stepping after pharmacotherapy is unknown. For the neonatally spinalized rat
      model, the 5-HT(2C) receptor agonist 1-(m-chlorophenyl)-piperazine hydrochloride
      (mCPP) increases the number of WS steps taken when administered to adult rats
      spinalized as neonates (mCPP+) though not all animals showed this effect (mCPP-).
      Since no differences in the behavior of the animals off-drug has been
      demonstrated, it is unclear why acute administration of 5-HT affects only a
      subset of animals. One possibility is that differences in cortical organization
      between mCPP+ and mCPP- may contribute to the differences in the functional
      effect of mCPP. To test this, we recorded from single neurons in the deafferented
      hindlimb sensorimotor cortex during passive sensory stimulation of the cutaneous
      surface of the forepaws and during active sensorimotor stimulation of the
      forepaws while the animals locomoted on a motorized treadmill. Our results show
      that neurons recorded from mCPP+ animals increased their responsiveness to both
      passive and active stimulation off-drug in comparison to neurons from mCPP-
      animals. These data suggest that differences in the cortical organization of
      mCPP+ compared to mCPP- animals may be at least partially responsible for the
      effect of a 5-HT(2C) receptor agonist on functional outcome.

PMID- 23159335
TI  - Impact of polyclonal anti-CD3/CD28-coated magnetic bead expansion methods on T
      cell proliferation, differentiation and function.
AB  - BACKGROUND AND AIMS: The aim of the present study was to compare several in vitro
      anti-CD3/CD28-coated magnetic bead expansion methods as a means of improving T
      cell recovery and to evaluate the impact of the respective methods on T cell
      viability, differentiation and function. The effect of the respective expansion
      protocols on cytokine production and cytotoxicity was also characterized.
      METHODS: Peripheral blood mononuclear cells were isolated from healthy donors,
      expanded for 7 days by different methods in vitro and then counted. T cell
      viability, phenotype and differentiation status were determined by flow
      cytometry. The cytotoxicity of collected cells was evaluated by a non-radioactive
      assay. RESULTS: An equal bead-to-cell ratio in the presence of IL-2, IL-7 and IL
      15 generated the highest T cell yields (median 4.75-fold increase [range 4.10
      6.25], P=0.043) with a median of 79.20% viable cells (range 70.00%-80.30%). By
      contrast, a high bead-to-cell ratio (3:1) favored the selection of central memory
      T cells (CD4: 0.44 [0.40-1.69]; CD8: 0.77 [0.42-1.19], P=0.043) with increased
      interferon-gamma (IFN-gamma) production following re-stimulation (48.5% [42.1%
      68.2%], P=0.043) and also a trend towards enhanced cytotoxicity against target
      cells (10:1 ratio: 61.80% [40.80%-80.00%], P=0.068). CONCLUSIONS: An equal bead
      to-cell ratio is optimal in keeping the balance between promoting proliferations
      and preserving cellular vitality and the combination of homeostatic cytokines
      further improved cell output, whereas a high bead-to-cell ratio favored the
      production of bioactive cells.

PMID- 23159336
TI  - Complement activation associated with polysorbate 80 in beagle dogs.
AB  - Polysorbate 80 (Tween(r) 80) is the most extensively used surfactant in
      parenteral drug formulation. Its application as an adjunct for intravenous drug
      administration is approved by the Food and Drug Administration. However, severe
      hypersensitive reactions, which are typical non-immune anaphylactic reactions
      (pseudoallergy) characterized by the release of histamine and unvaried IgE
      antibodies, have been associated with Tween(r) 80. In order to explore the non
      immune anaphylactic mechanisms of Tween(r) 80, we performed in vivo experiments
      to assess the changes in physiological and hematologic indicators after
      intravenous injection of Tween(r) 80 into dogs. Tween(r) 80 induced the release
      of histamine, and a 2-fold increase in SC5b-9, 2.5-fold increase in C4d, 1.3-fold
      increase in Bb, while IgE remained unchanged. It also produced changes in
      pulmonary pressure, systemic pressure and ECG. In in vitro experiments, Tween(r)
      80 was incubated with dog serum in the presence of an inhibitor of complement
      activation (EGTA/Mg(2+)). Under these conditions, Tween(r) 80 increased the
      contents of C4d and Bb. The results of this study reveal that Tween(r) 80 can
      cause cardiopulmonary distress in dogs and activate the complement system through
      classical and alternative pathways as indicated in both in vivo and in vitro
      preparations. Moreover, they demonstrate the utility of the beagle dog as an
      animal model for the study of complement activation-related pseudoallergy. These
      findings raise concerns with regard to the indiscriminate use of Tween(r) 80 in
      clinical applications.

PMID- 23159334
TI  - TiF1-gamma plays an essential role in murine hematopoiesis and regulates
      transcriptional elongation of erythroid genes.
AB  - Transcriptional regulators play critical roles in the regulation of cell fate
      during hematopoiesis. Previous studies in zebrafish have identified an essential
      role for the transcriptional intermediary factor TIF1gamma in erythropoiesis by
      regulating the transcription elongation of erythroid genes. To study if TIF1gamma
      plays a similar role in murine erythropoiesis and to assess its function in other
      blood lineages, we generated mouse models with hematopoietic deletion of
      TIF1gamma. Our results showed a block in erythroid maturation in the bone marrow
      following tif1gamma deletion that was compensated with enhanced spleen
      erythropoiesis. Further analyses revealed a defect in transcription elongation of
      erythroid genes in the bone marrow. In addition, loss of TIF1gamma resulted in
      defects in other blood compartments, including a profound loss of B cells, a
      dramatic expansion of granulocytes and decreased HSC function. TIF1gamma exerts
      its functions in a cell-autonomous manner as revealed by competitive
      transplantation experiments. Our study therefore demonstrates that TIF1gamma
      plays essential roles in multiple murine blood lineages and that its function in
      transcription elongation is evolutionally conserved.

PMID- 23159337
TI  - Effusanin C inhibits inflammatory responses via blocking NF-kappaB and MAPK
      signaling in monocytes.
AB  - Effusanin C, a constituent of Isodon japonicus, has been used in oriental
      countries as a traditional folk medicine to treat inflammatory diseases, but its
      mechanism of action remains unknown. Here, we investigate the inhibitory activity
      of effusanin C in inflammatory monocytes. Effusanin C markedly inhibited the
      production of inflammatory mediators including nitric oxide, IL-1beta, and TNF
      alpha in macrophages and dendritic cells. Furthermore, molecular studies showed
      that effusanin C inhibited phosphorylation of p38, JNK, and ERK, degradation of
      IkappaBbeta, and nuclear translocation of NF-kappaB p50/p65 in these cells. Taken
      together, these data show that effusanin C inhibits inflammatory responses by
      blocking NF-kappaB and MAPK signalings in monocytes.

PMID- 23159339
TI  - UPLC-MS/MS determination in blood of a mixed-drug fatal intoxication: a case
      report.
AB  - Trends in forensic toxicology show the introduction of rapid analytical methods
      for the simultaneous quantitative analysis of drugs. The authors present a fatal
      case involving a 32-year-old male, found dead in bed by his mother, with several
      blue, white and orange pills next to the body. Empty tablets were found in the
      trash bin and a suicide note was on the desk. He was diagnosed with bipolar
      disorder and had been under psychiatric treatment, having repeatedly demonstrated
      intent to commit suicide. A rapid method was developed to determine 55 different
      medicines and 32 benzodiazepines in blood by ultra-performance liquid
      chromatography (UPLC) coupled with tandem mass spectrometry (MS/MS) with
      electrospray ionization source in positive and negative ion mode. Chromatographic
      analysis was preceded by an optimized solid-phase extraction procedure using
      Oasis((r)) HLB (3 cc, 60 mg) extraction columns. The extracted analytes were
      separated by UPLC (Waters) with a reversed-phase Acquity UPLC((r)) HSS T3
      (2.1*100 mm id, 1.8 MUm) column with acetonitrile and 0.1% formic acid in water
      as mobile phase, at 0.5 mL/min flow rate and a chromatographic run-time of 8 min.
      Analytes detection was achieved with a triple-quadrupole mass spectrometer in
      positive and negative electrospray ionization mode with multiple reaction
      monitoring (MRM). Two MRM transitions were monitored for each target-compound and
      one for each deuterated internal standards. Toxicological results showed high
      blood concentrations of antipsychotics (haloperidol, olanzapine and quetiapine),
      antidepressants (fluoxetine and paroxetine) and anxiolytics (bromazepam and
      lorazepam). Risperidone and other benzodiazepines were also present in
      therapeutic concentrations. Neither alcohol nor illicit drugs were present in the
      analyzed samples. The UPLC-MS-MS method showed to be appropriate for screening,
      identification and quantitation of antipsychotics, antidepressants, anxiolytics
      and antiepileptic drugs in blood after intake of therapeutic as well as toxic
      doses. The autopsy and toxicological results led the pathologist to rule that
      death was due to a mixed-drug intoxication. The manner of death was determined to
      be suicide.

PMID- 23159338
TI  - TLR agonists are highly effective at eliciting functional memory CTLs of effector
      memory phenotype in peptide immunization.
AB  - Given the importance of memory cytotoxic T lymphocytes (CTLs) in eliminating
      altered self-cells, including virus-infected and tumor cells, devising effective
      vaccination strategies for generating memory CTLs is a priority in the field of
      immunology. Herein, we elaborate upon a novel boosting approach that utilizes
      synthetic peptides and Toll-like receptor (TLR) agonists as adjuvants to generate
      sufficient numbers of memory CTLs to protect against infection in mice. Peptide
      boosting with lipopolysaccharide (LPS), a TLR4-ligand, has been shown to
      progressively enhance memory CTLs. Whether this result is strictly dependent on
      activation of TLR4 or can be similarly achieved by signaling through other TLRs
      is of practical interest in vaccine development but is yet unknown. In this
      report, we present evidence that intravenous peptide boosting together with TLR3
      and TLR9 agonists (Poly IC and CpG, respectively) is highly effective and induces
      large quantities of memory CTLs of effector memory phenotype after three boosts.
      Compared to LPS, CpG and Poly IC generate more robust immune responses after the
      first and second boosts, indicating that a protective level of CTLs might be
      achieved with fewer boosts when CpG or Poly IC is used. Lastly, the resultant
      memory CTLs from boosting with different TLR agonists as adjuvant are equally
      protective against pathogen challenge and are not immune senescent. Therefore,
      TLR agonists are effective adjuvants in intravenous peptide boosting for the
      generation of functional memory CTLs.

PMID- 23159340
TI  - Dismantling the Justice Silos: avoiding the pitfalls and reaping the benefits of
      information-sharing between forensic science, medicine and law.
AB  - Forensic science is increasingly relied on by police and the courts to exonerate
      the innocent and to establish links to crime. With this increased reliance the
      potential for unjust outcomes increases, especially in serious matters for two
      reasons. The more serious the matter, the more likely that evidence mishandling
      can lead to wrongful imprisonment, and the more likely the personnel involved
      will be multi-disciplinary (police, medicine, law, forensic science), and multi
      organisational (Health, Justice, private legal/medical, police). The importance
      of identifying effective multi-organisational interactions was highlighted in the
      recent wrongful imprisonment of an Australian male for a sexual assault he did
      not commit. One factor that led to this unjust outcome was the justice silo
      effect: where forensic practitioners from different agencies operate in isolation
      (rarely communicating or sharing information/knowledge). In this paper we discuss
      findings from the Interfaces Project designed to assess the extent of the justice
      silos within Australia. We interviewed 103 police, forensic scientists, lawyers,
      judges, coroners, pathologists and forensic physicians Australian-wide. Five main
      themes were identified in the data: the silo effect was only partial and in each
      jurisdiction some form of inter-agency communication was actively occurring;
      inter-agency meetings were more common in homicide than sexual assault cases;
      forensic physicians were semi-invisible; there had been considerable momentum
      over the past ten years for practice improvement groups, and; practitioners gain
      more benefits than pitfalls from inter-agency information-sharing. Based on these
      findings, five recommendations are made for improving practice. 

PMID- 23159341
TI  - The gut microbiota, obesity and insulin resistance.
AB  - The human gut is densely populated by commensal and symbiotic microbes (the "gut
      microbiota"), with the majority of the constituent microorganisms being bacteria.
      Accumulating evidence indicates that the gut microbiota plays a significant role
      in the development of obesity, obesity-associated inflammation and insulin
      resistance. In this review we discuss molecular and cell biological mechanisms by
      which the microbiota participate in host functions that impact the development
      and maintenance of the obese state, including host ingestive behavior, energy
      harvest, energy expenditure and fat storage. We additionally explore the diverse
      signaling pathways that regulate gut permeability and bacterial translocation to
      the host and how these are altered in the obese state to promote the systemic
      inflammation ("metabolic endotoxemia") that is a hallmark of obesity and its
      complications. Fundamental to our discussions is the concept of "crosstalk",
      i.e., the biochemical exchange between host and microbiota that maintains the
      metabolic health of the superorganism and whose dysregulation is a hallmark of
      the obese state. Differences in community composition, functional genes and
      metabolic activities of the gut microbiota appear to distinguish lean vs obese
      individuals, suggesting that gut 'dysbiosis' contributes to the development of
      obesity and/or its complications. The current challenge is to determine the
      relative importance of obesity-associated compositional and functional changes in
      the microbiota and to identify the relevant taxa and functional gene modules that
      promote leanness and metabolic health. As diet appears to play a predominant role
      in shaping the microbiota and promoting obesity-associated dysbiosis, parallel
      initiatives are required to elucidate dietary patterns and diet components (e.g.,
      prebiotics, probiotics) that promote healthy gut microbiota. How the microbiota
      promotes human health and disease is a rich area of investigation that is likely
      to generate fundamental discoveries in energy metabolism, molecular endocrinology
      and immunobiology and may lead to new strategies for prevention of obesity and
      its complications.

PMID- 23159342
TI  - [Virological tools for the diagnosis, the prognosis and the surveillance of
      congenital cytomegalovirus infections].
AB  - Cytomegalovirus (CMV) infection is the main cause of congenital infection in
      industrialized countries. The virological tools used for the diagnosis of
      congenital CMV are serology for diagnosis of primary infection in the mother, CMV
      PCR in amniotic fluid for diagnosis of fetal infection, PCR in urine or saliva
      for neonatal diagnosis and PCR in dried blood spots on Guthrie cards for
      retrospective diagnosis in young children. The prognostic value of viral load in
      amniotic fluid, fetal blood and neonatal blood will be discussed. The performance
      of the virological tests for antenatal or postnatal screening of congenital CMV
      will also be discussed.

PMID- 23159343
TI  - [What do pediatricians and general practitioners think about the implementation
      of meningococal B vaccination in France?].
AB  - BACKGROUND: To assess the acceptability of a vaccine against meningococcus B by
      pediatricians and GP and to analyze how the vaccine could be implemented in
      France, InfoVac-France has set up a national survey. METHODS: An email explained
      the purpose of this study and the practitioners of InfoVac-France network
      answered an online questionnaire (e-CRF). RESULTS: Of the 6905 pediatricians and
      GP who saw the mail sent by InfoVac-France between 11 and 24 January, 2012, 1351
      (13.5 %) completed the e-CERF : 361 GP (26.7%), 797 pediatricians (59%) and 193
      other doctors (14.3%). The majority of practitioners (96.1%) believe that is
      important to implement a vaccine against meningococcus B in the French
      immunization schedule. In 80.5% of cases, practitioners do not want to vaccine
      three times routinely during a single consultation and more than half (53.5%)
      would prefer to use this vaccine alone. The best schedule of primary vaccination
      (80.6%) is the injection at 3, 5 and 6 months. The arguments considered likely to
      encourage parents to accept the vaccination would be the incidence of the
      disease, severity of meningitis (82.1%) and the rapid mortality (82.8%).
      CONCLUSION: This survey by InfoVac-France shows that the practitioners know the
      epidemiology of meningococcal B invasive disease in children. They would support
      the implementation of this vaccine for children under 2 years with a primary
      vaccination at 3, 5 and 6 months.

PMID- 23159344
TI  - The suppression of repetition enhancement: a review of fMRI studies.
AB  - Repetition suppression in fMRI studies is generally thought to underlie
      behavioural facilitation effects (i.e., priming) and it is often used to identify
      the neuronal representations associated with a stimulus. However, this pays
      little heed to the large number of repetition enhancement effects observed under
      similar conditions. In this review, we identify several cognitive variables
      biasing repetition effects in the BOLD response towards enhancement instead of
      suppression. These variables are stimulus recognition, learning, attention,
      expectation and explicit memory. We also evaluate which models can account for
      these repetition effects and come to the conclusion that there is no one single
      model that is able to embrace all repetition enhancement effects. Accumulation,
      novel network formation as well as predictive coding models can all explain
      subsets of repetition enhancement effects.

PMID- 23159346
TI  - Incorporation of polyinosine-polycytidylic acid enhances cytotoxic T cell
      activity and antitumor effects by octaarginine-modified liposomes encapsulating
      antigen, but not by octaarginine-modified antigen complex.
AB  - In a previous study, we reported on the efficient delivery of an antigen to the
      cytosol and a specific-antigen presentation on MHC class I in dendritic cells by
      rationally controlling the intracellular trafficking of ovalbumin (OVA), a model
      antigen, with stearylated octaarginine-modified liposomes (R8-Lip/OVA). However,
      no significant difference in antitumor effects against E.G7-OVA, OVA expressed
      lymphoma, was observed between R8-Lip/OVA and an electrostatic complex of R8 and
      OVA (R8/OVA-Com). In this study, we hypothesized that use of adjuvants clarified
      the difference in immune responses between R8-Lip/OVA and R8/OVA-Com, and
      selected polyinosine-polycytidylic acid (polyI:C) as an adjuvant. Cytotoxic T
      lymphocyte (CTL) activity of the polyI:C and OVA encapsulated R8-Lip (R8
      Lip/PIC/OVA) was drastically enhanced compared to R8-Lip/OVA and complete
      Freund's adjuvant with OVA. Moreover, the incorporation of polyI:C clearly was
      critical for the difference in antitumor effects and CTL activities between R8
      Lip/OVA and R8/OVA-Com. These findings suggest that the carriers that are
      incorporated polyI:C has a great influence on the induction of cellular immunity
      in vivo.

PMID- 23159345
TI  - Optimization of thermosensitive chitosan hydrogels for the sustained delivery of
      venlafaxine hydrochloride.
AB  - Chitosan/glycerophosphate disodium (GP) thermosensitive hydrogels were prepared
      for the sustained delivery of venlafaxine hydrochloride (VH) and optimization of
      this formulation was mainly studied. Release mechanism was investigated by
      applying various mathematical models to the in vitro release profiles. Overall,
      drug release from the hydrogels showed best fit in first-order model and drug
      release mechanism was diffusion-controlled release. Optimization of VH
      chitosan/GP thermosensitive hydrogels was conducted by using a three-level three
      factorial Box-Behnken experimental design to evaluate the effects of considered
      variables, the strength of the formulation, chitosan concentration and GP amount,
      on the selected responses: cumulative percentage drug release in 1h, 24h and the
      rate constant. It presented that higher strength and GP concentration resulted in
      higher initial release and rate constant, which supported the hypothesis that the
      kinetic gelation mechanism of this system was nucleation and growth. Drug release
      profiles illustrated that controlled drug delivery could be obtained over 24h,
      which confirmed the validity of optimization. In vivo pharmacokinetic study was
      investigated and it demonstrated that compared with VH solution, chitosan/GP
      thermosensitive hydrogels had a better sustained delivery of VH.

PMID- 23159347
TI  - Hydrogen peroxide increases nerve-evoked contractions in mouse tail artery by an
      endothelium-dependent mechanism.
AB  - Reactive oxygen species contribute to regulating the excitability of vascular
      smooth muscle. This study investigated the actions of the relatively stable
      reactive oxygen species, H(2)O(2), on nerve-evoked contractions of mouse distal
      tail artery. H(2)O(2) (10-100 MUM) increased nerve-evoked contractions of
      isometrically mounted segments of tail artery. Endothelium denudation increased
      nerve-evoked contractions and abolished the facilitatory effect of H(2)O(2).
      Inhibition of nitric oxide synthase with L-nitroarginine methyl ester (0.1mM)
      also increased nerve-evoked contractions and reduced the late phase of H(2)O(2)
      induced facilitation. H(2)O(2)-induced facilitation of nerve-evoked contractions
      depended, in part, on synthesis of prostanoids and was reduced by the
      cyclooxygenase inhibitor indomethacin (1 MUM) and the thromboxane A(2) receptor
      antagonist SQ 29548 (1 MUM). H(2)O(2) increased sensitivity of nerve-evoked
      contractions to the alpha(2)-adrenoceptor antagonist idazoxan (0.1 MUM) but not
      to the alpha(1)-adrenoceptor antagonist prazosin (10nM). Idazoxan and the
      alpha(2C)-adrenoceptor antagonist JP 1302 (0.5-1 MUM) reduced H(2)O(2)-induced
      facilitation. H(2)O(2) induced facilitation of nerve-evoked contractions was
      abolished by the non-selective cation channel blocker SKF-96365 (10 MUM),
      suggesting it depends on Ca(2+) influx. In conclusion, H(2)O(2)-induced increases
      in nerve-evoked contractions depended on an intact endothelium and were mediated
      by activating thromboxane A(2) receptors and by increasing the contribution of
      alpha(2)-adrenoceptors to these responses.

PMID- 23159348
TI  - Change detection for the study of object and location memory.
AB  - Seven adult human participants were tested in change detection tasks for object
      and location memory with large and small sets of four different stimulus types.
      Blocked tests demonstrated that participants performed similarly in separate
      object and location tests with matched parameters and displays. In mixed tests,
      participants were informed that they would be tested with either object changes
      or location changes; surprisingly, they were nearly as accurate remembering both
      objects and locations as when either was tested alone. By contrast, in the large
      set condition, performance was lower than baseline on surprise probe test trials
      in which participants were tested (on 13% of trials) with the change type
      opposite to the present block (e.g., location probe trials during the object
      change block). These probe-test results were further supported by the reduction
      in probe-baseline differences when tested with small sets (6) of these item
      types. Small sets required remembering locations and objects to resolve object
      location confounds. Together these results show that humans can remember both
      objects and locations with little loss of accuracy when instructed to do so, but
      do not learn these contextual associations without instruction.

PMID- 23159349
TI  - Screening, identification, and support of gender non-conforming children and
      families.

PMID- 23159350
TI  - The botryoidal microcapsule: a novel tissue scaffold.
AB  - BACKGROUND/AIMS: Due to the semi-permeable membrane and biocompatibility,
      microcapsules have a very promising future in cell transplantation, drug carrier
      and large-scale cell culture. However, the current design prevents it from
      playing a role in tissue scaffold. METHODOLOGY: To address this pitfall, we
      invented a self-assembled botryoidal microcapsule by means of electrostatic
      interactions. The diameter of the scaffold was adjustable between 1 and 5cm,
      while that of the standard microcapsule is ordinarily 500um. RESULTS: Tests
      showed that it had better mechanical strength, as well as characteristics of
      biocompatibility and permeability. CONCLUSIONS: A botryoidal microcapsule is also
      effective at blocking the entrance of IgG and has the potential to function both
      as a favorable carrier and as a scaffold for artificial organs.

PMID- 23159351
TI  - Retrospective analysis of protective stoma after low anterior resection for
      rectal cancer with total mesorectal excision: three-year follow-up results.
AB  - BACKGROUND/AIMS: Anastomotic leakage is a complication of low anterior resection
      (LAR) for rectal cancer with total mesorectal excision (TME). This study
      evaluated the need for a protective stoma by a three-year follow-up. METHODOLOGY:
      A retrospective study of 56 LAR patients was conducted. Thirty patients (53.6%)
      had a protective stoma. C-reactive protein (CRP), interleukin 6 (IL-6) and tumor
      necrosis factor (TNF) in peripheral blood on the first and third day after
      surgery were compared, in addition to short-term and later complications, long
      term mortality and quality of life (QOL). RESULTS: There was significant
      difference between patients with and without a stoma in CRP, IL-6 on the third
      day after surgery (p<0.05). Anastomotic leakage occurred in two patients (6.7%)
      with a stoma and seven (26.9%) without (p=0.039). The incidence of leaks
      requiring re-operation was significantly lower with a stoma (p=0.012). After a
      mean follow-up of three years, there was no difference in long-term mortality,
      survival or scores on QOL questionnaires. CONCLUSIONS: A protective stoma can
      reduce the stress reaction, promote recovery of bowel function and reduce
      anastomotic leakage and re-operation rates in LAR for rectal cancer with TME. No
      significant difference was observed in long-term mortality or QOL.

PMID- 23159352
TI  - Thermal ablation for partial splenectomy hemostasis, spleen trauma, splenic
      metastasis and hypersplenism.
AB  - Many studies have been conducted on splenic thermal ablation for partial
      splenectomy hemostasis, spleen trauma, splenic metastasis and hypersplenism. In
      this article, we review the evolution and current status of radiofrequency and
      microwave ablation in the treatment of spleen diseases. All publications from
      1990 to 2011 on radiofrequency and microwave ablation for partial splenectomy
      hemostasis, spleen trauma, splenic metastasis and hypersplenism were retrieved by
      searching PubMed. Thermal ablation in the spleen for partial splenectomy
      hemostasis, spleen trauma, splenic metastasis and hypersplenism can preserve part
      of the spleen and maintain splenic immunologic function. Thermal ablation for
      assisting hemostasis in partial splenectomy minimizes blood loss during
      operation. Thermal ablation for spleen trauma reduces the number of splenectomy
      and the amount of blood transfusion. Thermal ablation for splenic metastasis is
      minimally invasive and can be done under the guidance of an ultrasound, which
      helps shorten the recovery time. Thermal ablation for hypersplenism increases
      platelet (PLT) and white blood cell (WBC) counts and improves liver function. It
      also helps to maintain splenic immunologic function and even improves splenic
      immunologic function in the short-term. In conclusion, thermal ablative
      approaches are promising for partial splenectomy hemostasis, spleen trauma,
      splenic metastasis and hypersplenism. In order to improve therapeutic effects,
      directions for future studies may include standardized therapeutic indications,
      prolonged observation periods and enlarged sample sizes.

PMID- 23159353
TI  - Health-related quality of life during postoperative chemoradiotherapy with oral
      uracil-tegafur and leucovorin in rectal cancer patients.
AB  - BACKGROUND/AIMS: The objective of this study was to report on the quality of life
      of locally advanced rectal cancer patients that were treated with uracil-tegafur
      (UFT)/leucovorin (LV)-based concurrent chemoradiotherapy. METHODOLOGY: Twenty
      five patients were enrolled into this prospective study. Radiotherapy (50.4Gy)
      was given with concurrent UFT (300mg/m2/day) and LV (30mg/day). Turkish versions
      of EORTC-QLQC30 and EORTC QLQCR38 were applied at the beginning (HRQoL-1) and at
      the end (HRQoL-2) of chemoradiotherapy. Paired samples t-test was used to compare
      the difference of means for each scale between HRQoL1 and HRQoL2 and p values
      <0.05 were considered statistically significant. RESULTS: Study compliance was
      80.6%. From baseline to the end of chemoradiotherapy, the mean scores of dyspnea
      (p=0.006) diarrhea (p=0.005) and micturition (p=0.005) increased significantly.
      Chemotherapy side effects also increased at the end of therapy (p=0.07). Seventy
      six percent (76%) of male patients replied to questions related to sexual
      problems and functions, whereas no female patients replied. CONCLUSIONS:
      Although, diarrhea and micturition are the major problems, quality of life scores
      indicate that concurrent oral fluoropyrimidine-based chemoradiotherapy is a
      feasible treatment.

PMID- 23159355
TI  - Meta-analysis: the relationship between TNF-alpha polymorphisms and
      susceptibility to primary biliary cirrhosis.
AB  - BACKGROUND/AIMS: To investigate the possible influence of TNF-alpha gene promoter
      polymorphisms in conferring a predisposition to PBC patients. METHODOLOGY: We
      performed a meta-analysis of nine articles searched from PubMed up to July 2010
      that investigated the association between two TNF-alpha polymorphisms (-308 and 
      238) and PBC. RESULTS: The data showed no significant association between TNF
      alpha-308, -238 gene polymorphisms and the susceptibility to PBC in the global
      group (OR=0.95, 95%CI=0.80-1.13, p=0.55; OR=1.00, 95%CI=0.65-1.55, p=0.99,
      respectively). Stratified by sub-groups (European, American, Asian), TNF -308
      minor allele, but not -238, was found to be a protective factor in the European
      population (OR= 0.81, 95%CI=0.67-0.99, p=0.04; OR=0.99, 95%CI=0.55-1.77, p=0.97,
      respectively). Moreover, no significant difference was observed between TNF-alpha
      308 alleles and PBC when stratified by histological stages (stages I-II, OR=0.68,
      95%CI=0.32-1.48, p=0.33; stages III-IV, OR=0.69, 95%CI=0.41-1.15, p=0.15).
      CONCLUSIONS: TNF-alpha promoter polymorphisms might not be associated with PBC
      risk. However, studies with larger population of varying ethnicity and stratified
      by clinical and laboratory characteristics are needed to validate our findings.

PMID- 23159354
TI  - Heterotopic pancreas autotransplantation with spleen for uncontrollable
      hemorrhagic pseudocyst and disabling pain in chronic pancreatitis.
AB  - BACKGROUND/AIMS: In this study, we report on a heterotopic segmental pancreatic
      autotransplantation (HPAT) with spleen for alcoholic chronic pancreatitis with
      uncontrollable hemorrhagic pseudocyst and complete portal venous obstruction. The
      patient was a 72-year-old man who had an alcoholic chronic pancreatitis with
      severe abdominal pain and hemorrhagic pseudocyst. The first bleeding from a
      pseudoaneurism of the gastro-duodenal artery (GDA) to the cyst of pancreas head
      was stopped by interventional radiology (IVR) at our hospital on May 2010. The
      second bleeding happened with severe abdominal pain on February 15th, 2011; he
      was admitted on February 17. The IVR was not successful. METHODOLOGY: There were
      two problems for the operation. The first was the severe inflammation and the
      second was the control of hemorrhage from GDA. We were afraid of the
      postoperative hemorrhage due to the leakage of pancreatic juice in the pancreato
      duodenectomy (PD). Therefore, we chose the HPAT as a solution for postoperative
      hemorrhage and severe abdominal pain. After complete duodeno-pancreatectomy with
      spleen, we performed HPAT with spleen on March 8, 2011. The pancreatic duct
      reconstruction was performed by Roux-en-Y anastomosis to the jejunum. RESULTS:
      The postoperative course was uneventful. The abdominal pain had resolved
      completely and the patient remained normoglycemic after HPAT. CONCLUSIONS: We
      conclude that HPAT is a useful option for hemorrhagic pseudocyst of the pancreas
      head with severe abdominal pain of chronic pancreatitis.

PMID- 23159356
TI  - The correlation between insulin-like growth factor II mRNA binding protein 3
      expression in hepatocellular carcinoma and prognosis.
AB  - BACKGROUND/AIMS: The study aims to explore the expression of IMP3 in HCC and the
      correlation between its expression and prognosis. METHODOLOGY: We collected
      several clinical and pathological files including 92 cases of HCC and 58 cases of
      adjacent liver tissues. Expression of IMP3 in these tissues was detected by
      immunohistochemistry, while compared with clinicopathological characteristics and
      expression of Ki-67. A chi2 test was used to analyze the relationship between
      expression of IMP3 and clinicomicronpathologic factors. The Kaplan-Meier survival
      curve was used to calculate survival rate. A Cox analysis was used to evaluate
      the relationship between index and patients' lifetime. RESULTS: The positive rate
      of IMP3 in HCC tissues was significantly higher than that in adjacent tissues.
      The expression of IMP3 was related to the histological differentiation of HCC,
      metastasis, the stage of ACJJ, the expression of Ki-67 and survival. The ACJJ
      stage, metastases and the expression of IMP3 were independent factors for the HCC
      patients' survival. CONCLUSIONS: IMP3, which is associated with tumor formation,
      invasion, tumor cell proliferation and so on, may become the target for
      inhabiting cell proliferation and the biomarker for predicting prognosis.

PMID- 23159357
TI  - Tuberculosis skin test, but not interferon-gamma-releasing assays is affected by
      BCG vaccination in HIV patients.
AB  - OBJECTIVE: Of this study was to compare the results of tuberculin skin test (TST)
      with two interferon-gamma releasing-assays (IGRA) in a cohort of HIV positive
      patients, to analyze impact of prior Bacille-Calmette-Guerin (BCG)-vaccination.
      METHODS: Prospective cross sectional study, enrolling only asymptomatic adult HIV
      infected outpatients from a large German University hospital clinic. All
      participants were simultaneously tested for latent tuberculosis infection (LTBI)
      by QuantiFERON-TB Gold, T-SPOT.TB and TST. Only individuals with available
      definite results (positive/negative, indeterminates excluded) from all three test
      systems and recalling BCG-vaccination status by interview questionnaire were
      evaluated. RESULTS: From 286 study participants, 133 were evaluable; BCG
      vaccination history was positive for 18 individuals, and negative for 115. The
      proportion of individuals with a positive TST was significantly higher for
      vaccinated (n = 6, 33.3%) than for unvaccinated individuals (n = 13, 11.3%, p =
      0.013). There were no significant differences in the proportion of patients with
      CDC stage C, origin from a TB endemic country or in the CD4 count between the two
      groups. CONCLUSION: TST but not IGRAs interfered significantly with prior BCG
      vaccination in a cohort of HIV infected individuals from a low prevalence TB
      country. Therefore IGRA should preferentially be used for LTBI-testing in BCG
      vaccinated adult HIV-patients.

PMID- 23159358
TI  - Role of CYP2C9 polymorphism in phenytoin-related metabolic abnormalities and
      subclinical atherosclerosis in young adult epileptic patients.
AB  - PURPOSE: We investigated the influence of the CYP2C9 polymorphism on the lipid
      profile, insulin resistance, and subclinical atherosclerosis in young epileptic
      patients. METHODS: We performed a cross-sectional study to evaluate the
      association between CYP2C9 polymorphism and lipid profile, glucose homeostasis,
      and subclinical atherosclerosis in young epileptic patients via the ankle
      brachial index. RESULTS: The frequencies of CYP2C9*1 (CYP2C9 wild type gene) and
      CYP2C9*3 (CYP2C9 polymorphism gene) were 75% and 25%, respectively. The mean
      serum total triglyceride and LDL levels were significantly higher in the wild
      type gene subjects than in the CYP 2C9 polymorphism gene subjects. Also, the CYP
      2C9 polymorphism had marginally significant lower mean serum HDL levels than the
      wild type gene subjects. No patients with CYP 2C9 polymorphism gene had elevated
      fasting blood sugar, and insulin resistance was found in only 10 of the 75
      subjects. The mean ABI was statistically significantly lower in the wild type
      subjects than in the CYP2C9 polymorphism gene subjects. CONCLUSION: Our study
      indicates that young epileptic patients with the CYP2C9 polymorphism gene have a
      low risk of subclinical atherosclerosis.

PMID- 23159359
TI  - Challenges and recommendations for obtaining chemical structures of industry
      provided repurposing candidates.
AB  - There is an expanding amount of interest directed at the repurposing and
      repositioning of drugs, as well as how in silico methods can assist these
      endeavors. Recent repurposing project tendering calls by the National Center for
      Advancing Translational Sciences (USA) and the Medical Research Council (UK) have
      included compound information and pharmacological data. However, none of the
      internal company development code names were assigned to chemical structures in
      the official documentation. This not only abrogates in silico analysis to support
      repurposing but consequently necessitates data gathering and curation to assign
      structures. Here, we describe the approaches, results and major challenges
      associated with this.

PMID- 23159360
TI  - Novel antitussive strategies.
AB  - Acute and chronic cough represent one of the most common symptoms of medical
      importance but effective pharmacotherapy is, to all intents and purposes, absent.
      Numerous initiatives targeting the recently discovered tussive pathways are in
      progress. Here, we review the current antitussive armamentarium and provide an
      update on the novel strategies and compounds in development.

PMID- 23159361
TI  - Use of renal resistive index and semi-rigid ureteroscopy for managing symptomatic
      persistent hydronephrosis during pregnancy.
AB  - PURPOSE: The aim of this study was to evaluate the use of Doppler ultrasonography
      (DUS) and semi-rigid ureteroscopy (URS) for managing symptomatic persistent
      hydronephrosis during pregnancy. MATERIALS AND METHODS: The study included 19
      pregnant patients with unilateral symptomatic persistent hydronephrosis. All
      pregnant patients were assessed with conventional ultrasonography (US) followed
      by DUS for both kidneys. RESULTS: The mean patient age was 26 years (range 19
      40), and the gestational period was 24 weeks (range 16-33). There was a
      significantly higher mean resistive index in the kidneys with ureteral
      obstruction than in the contralateral normal kidneys. Spinal anesthesia was
      performed on 18 patients, while general anesthesia was performed on 1 patient.
      Endoscopically stones were found in 17 patients (89.5%), while no stone was found
      in 2 patients (10.5%). The stones were fragmented by holmium laser and retracted
      with forceps. After lithotripsy, a ureteral JJ stent was inserted in 8 of 17
      (47%) patients with ureteral stones. Intraoperatively, there were no obstetric
      complications, while ureteral perforation was seen in one patient. Two patients
      are still pregnant at the time of this writing, and 17 babies were born normally.
      CONCLUSIONS: Both RI and DeltaRI increase in unilateral symptomatic persistent
      hydronephrosis during pregnancy. Semi-rigid URS can be used successfully for
      diagnosis and treatment in these patients.

PMID- 23159362
TI  - Rationale use of unenhanced multi-detector CT (CT KUB) in evaluation of suspected
      renal colic.
AB  - OBJECTIVE: To assess the yield of non-contrast enhanced CT (CT KUB) across
      different ordering specialties and need of developing an algorithm for its
      rationale use. MATERIALS AND METHODS: We retrospectively reviewed 1550
      consecutive CT KUB studies requested for suspected renal colic carried out at a
      single institution in a calendar year. The data was analyzed for demographic
      characteristics, referring clinician and final diagnosis. Only patients with CT
      as primary imaging for clinically suspected reno-ureteral colic were included.
      Departments ordering these CT KUB examinations were divided into three divisions:
      Urologist, emergency room (ER) physician and others. RESULTS: Of 1550 CT KUB
      performed in the study period 766 met the inclusion criteria. Urologists (57%),
      followed by ER physicians (30%) mostly ordered the examination. The overall
      positive yield for urolithiasis was 64% (n = 490), rate of incidental/alternate
      findings was 15% (n = 116) and 21% (n = 160) were negative. Urologist has the
      highest positive yield of 67.4% (n = 295) followed by ER physician 67% (n = 152)
      and others 42.5% (n = 43); p < 0.001. Rate of incidental/alternate findings was
      highest in CT ordered by other specialties 23.7% (n = 24) followed by ER
      physician 17.6% (n = 40) and urologist 11.8% (n = 52); p = 0.005. CONCLUSION:
      There is statistically significant difference of yield across specialties. CT KUB
      as an initial imaging modality for suspected urolithiasis should be ordered in
      consultation with the urologist and ER physicians. Tool of good history taking
      and physical examination has proved to be essential steps in algorithm of
      ordering CT KUB, which can avoid unnecessary radiation exposure.

PMID- 23159363
TI  - An asymptomatic intraorbital foreign body for 30 years.
AB  - Intraorbital foreign bodies (IOFBs) are usually accompanied by notable skin
      wounds and/or ocular wounds, and often there is a clear history of a penetrating
      object. We report herein on a patient who had an asymptomatic IOFB for 30 years.
      To the best of our knowledge, there is only one other case of a patient with an
      IOFB for a longer asymptomatic period after the injury. IOFBs may be overlooked
      because a small penetrating wound may be accompanied by no signs of inflammation
      for many decades as in this patient's clinical course.

PMID- 23159364
TI  - An unusual cause of upper gastrointestinal bleeding.

PMID- 23159365
TI  - An uncommon malignancy of the esophagus.

PMID- 23159366
TI  - Vascular lesion in an adult mimicking esophageal varix.

PMID- 23159367
TI  - Increased risk of advanced neoplasms among asymptomatic siblings of patients with
      colorectal cancer.
AB  - BACKGROUND & AIMS: Colorectal cancer (CRC) is the second-most common cancer in
      Hong Kong. Relatives of patients with CRC have an increased risk of colorectal
      neoplasm. We assessed the prevalence of advanced neoplasms among asymptomatic
      siblings of patients with CRC. METHODS: Patients with CRC were identified from
      the Prince of Wales Hospital CRC Surgery Registry from 2001 to 2011.
      Colonoscopies were performed for 374 siblings of patients (age, 52.6 +/- 7.4 y)
      and 374 age- and sex-matched siblings of healthy subjects who had normal
      colonoscopies and did not have a family history of CRC (controls, 52.7 +/- 7.4
      y). We identified individuals with advanced neoplasms (defined as cancers or
      adenomas of at least 10 mm in diameter, high-grade dysplasia, with villous or
      tubulovillous characteristics). RESULTS: The prevalence of advanced neoplasms was
      7.5% among siblings of patients and 2.9% among controls (matched odds ratio
      [mOR], 3.07; 95% confidence interval [CI], 1.5-6.3; P = .002). The prevalence of
      adenomas larger than 10 mm was higher among siblings of patients than in controls
      (5.9% vs 2.1%; mOR, 3.34; 95% CI, 1.45-7.66; P = .004), as was the presence of
      colorectal adenomas (31.0% vs 18.2%; mOR, 2.19; 95% CI, 1.52-3.17; P < .001). Six
      cancers were detected among siblings of patients; no cancers were detected in
      controls. The prevalence of advanced neoplasms among siblings of patients was
      higher when their index case was female (mOR, 4.95; 95% CI, 1.81-13.55) and had
      distally located CRC (mOR, 3.10; 95% CI, 1.34-7.14). CONCLUSIONS: In Hong Kong,
      siblings of patients with CRC have a higher prevalence of advanced neoplasms,
      including CRC, than siblings of healthy individuals. Screening is indicated in
      this high-risk population. ClinicalTrials.gov number: NCT00164944.

PMID- 23159368
TI  - Transcriptional silencing of transposons by Piwi and maelstrom and its impact on
      chromatin state and gene expression.
AB  - Eukaryotic genomes are colonized by transposons whose uncontrolled activity
      causes genomic instability. The piRNA pathway silences transposons in animal
      gonads, yet how this is achieved molecularly remains controversial. Here, we show
      that the HMG protein Maelstrom is essential for Piwi-mediated silencing in
      Drosophila. Genome-wide assays revealed highly correlated changes in RNA
      polymerase II recruitment, nascent RNA output, and steady-state RNA levels of
      transposons upon loss of Piwi or Maelstrom. Our data demonstrate piRNA-mediated
      trans-silencing of hundreds of transposon copies at the transcriptional level. We
      show that Piwi is required to establish heterochromatic H3K9me3 marks on
      transposons and their genomic surroundings. In contrast, loss of Maelstrom
      affects transposon H3K9me3 patterns only mildly yet leads to increased
      heterochromatin spreading, suggesting that Maelstrom acts downstream of or in
      parallel to H3K9me3. Our work illustrates the widespread influence of transposons
      and the piRNA pathway on chromatin patterns and gene expression.

PMID- 23159369
TI  - Facilitators and impediments of the pluripotency reprogramming factors' initial
      engagement with the genome.
AB  - The ectopic expression of transcription factors can reprogram cell fate, yet it
      is unknown how the initial binding of factors to the genome relates functionally
      to the binding seen in the minority of cells that become reprogrammed. We report
      a map of Oct4, Sox2, Klf4, and c-Myc (O, S, K, and M) on the human genome during
      the first 48 hr of reprogramming fibroblasts to pluripotency. Three striking
      aspects of the initial chromatin binding events include an unexpected role for c
      Myc in facilitating OSK chromatin engagement, the primacy of O, S, and K as
      pioneer factors at enhancers of genes that promote reprogramming, and megabase
      scale chromatin domains spanned by H3K9me3, including many genes required for
      pluripotency, that prevent initial OSKM binding and impede the efficiency of
      reprogramming. We find diverse aspects of initial factor binding that must be
      overcome in the minority of cells that become reprogrammed.

PMID- 23159370
TI  - Anti-Candida albicans activity and pharmacokinetics of pogostone isolated from
      Pogostemonis Herba.
AB  - The present work was designed to evaluate the in vitro and in vivo anti-Candida
      activity of pogostone (PO), a natural product isolated from Pogostemon cablin
      (Blanco) Benth. PO showed potent in vitro activity against clinical Candida spp.
      isolates tested in this study. PO and the reference drug voriconazole (VRC) were
      equally effective against all the fluconazole-resistant Candida albicans strains,
      with MIC ranging from 3.1 MUg/ml to 50 MUg/ml. Besides, PO was fungicidal against
      all Candida isolates with MFC ranging from 50 MUg/ml to 400 MUg/ml. By contrast,
      VRC was fungistatic as it failed to elicit a fungicidal effect against the
      Candida spp. isolates at the highest tested concentration (400 MUg/ml).
      Furthermore, oral and topical PO administration effectively reduced the fungal
      load in vagina of vulvovaginal candidiasis mouse models. Topical PO
      administration (1.0-4.0 mg/kg) demonstrated higher activity against the
      vulvovaginal candidiasis than VRC (4.0 mg/kg). The pharmacokinetics and safety
      profile of PO were also investigated. The pharmacokinetics assay revealed that PO
      was easily absorbed after oral administration in mice, which might account for
      its in vivo anti-Candida effect. The acute toxicity test showed that the median
      lethal dose of PO in mice was 355 mg/kg, which was much higher than the daily
      dose used for the therapeutic experiments. This study demonstrated the potential
      of PO as a promising candidate for the treatment of Candida infections,
      particularly for vulvovaginal candidiasis.

PMID- 23159371
TI  - The Warburg effect: insights from the past decade.
AB  - Several decades ago, Otto Warburg discovered that cancer cells produce energy
      predominantly by glycolysis; a phenomenon now termed "Warburg effect". Warburg
      linked mitochondrial respiratory defects in cancer cells to aerobic glycolysis;
      this theory of his gradually lost its importance with the lack of conclusive
      evidence confirming the presence of mitochondrial defects in cancer cells.
      Scientists began to believe that this altered mechanism of energy production in
      cancer cells was more of an effect than the cause. More than 50 years later, the
      clinical use of FDG-PET imaging in the diagnosis and monitoring of cancers
      rekindled the interest of the scientific community in Warburg's hypothesis. In
      the last ten years considerable progress in the field has advanced our
      understanding of the Warburg effect. However, it still remains unclear if the
      Warburg effect plays a causal role in cancers or it is an epiphenomenon in
      tumorigenesis. In this review we aim to discuss the molecular mechanisms
      associated with the Warburg effect with emphasis on recent advances in the field
      including the role of epigenetic changes, miRNAs and post-translational
      modification of proteins. In addition, we also discuss emerging therapeutic
      strategies that target the dependence of cancer cells on altered energy
      processing through aerobic glycolysis.

PMID- 23159373
TI  - Synthesis of kifunensine thioanalogs and their inhibitory activities against HIV
      RT and alpha-mannosidase.
AB  - An efficient and practical synthesis of kifunensine thioanalogs 1a-c was
      reported. The bicyclic azasugars fused thiazolidin-4-one 4a-c as key
      intermediates were first synthesized in good yields of 74-80% via one-pot tandem
      Staudinger/aza-Wittig/cyclization by using the pivotal azidosugars 3a and 3b
      derived from D-mannose. Followed by double Pummerer rearrangements and
      deprotection, the target thiokifunensine 1a and its epimers 1b and 1c were
      obtained in good yields. Compounds 1a-c were preliminary evaluated for their HIV
      RT and alpha-mannosidase (Jack bean) inhibitory activities. The results showed
      that such compounds exhibited significant anti-HIV-RT inhibitory activity but
      poor inhibitory against alpha-mannosidase. To gain further insight into the
      inhibitory mechanism of compounds 1a-c, the analog compounds 9a-c were also
      prepared after deprotection from 4a-c, respectively. Activity comparison between
      compounds 1a-c and 9a-c suggests that the better activities of 1a-c than those of
      the 9a-c is possibly due to the additional carbonyl at thiazolidine-4-one ring in
      fused bicyclic azasugars.

PMID- 23159374
TI  - Structural elucidation of the exopolysaccharide produced by fungus Fusarium
      oxysporum Y24-2.
AB  - The extracellular polysaccharide FO1 was isolated from the fermentation broth of
      an endophytic fungus (Fusarium oxysporum) of Ipomoea pes-caprae. Its structural
      characteristics were studied by chemical and methylation analyses, and 1D and 2D
      (1)H and (13)C NMR spectroscopy. Results indicated that this exopolysaccharide
      consists of a disaccharide repeating unit with the following structure (n~111): [
      >2)-beta-D-Galf(1->6)-alpha-D-Glcp(1->](n).

PMID- 23159375
TI  - Uninformed clinical decisions resulting from lack of adherence assessment in
      children with new-onset epilepsy.
AB  - This study examined the relationship between nonadherence to antiepileptic drug
      (AED) therapy and clinical decision making in a cohort of 112 children with newly
      diagnosed epilepsy. Antiepileptic drug adherence was monitored using electronic
      monitoring over the first six months of therapy. The primary outcome measure was
      rate of uninformed clinical decisions as defined by the number of participants
      with AED dosage or drug changes to address continued seizures who demonstrated
      nonadherence prior to the seizure. Among the 52 (47%) participants who had an AED
      change for continued seizures, 30 (27% of the overall cohort) had imperfect
      medication adherence prior to their seizures. A quarter of the children with new
      onset epilepsy had uninformed medication changes because adherence was not
      rigorously assessed in clinical practice. The results highlight the importance of
      routinely assessing medication adherence in this population.

PMID- 23159376
TI  - Explanations given by people with epilepsy for using emergency medical services:
      a qualitative study.
AB  - Half of the people with epilepsy (PWE) in the UK experience seizures and 13-18%
      attend emergency medical services (EMS) annually. The majority of attendances are
      regarded as clinically unjustified. This study describes PWE explanations for
      using EMS. A nested qualitative study, part of a larger study based in three
      South London hospitals, was conducted. Semi-structured interviews were recorded,
      transcribed, and analyzed thematically. A seizure alone was not the main
      explanation for attending EMS; knowledge, experience, and confidence of those
      nearby on what to do and seizure context were important. Additionally, fears of
      sudden death held by the PWE and others were reported. From the patients'
      perspective, use of EMS is regarded as appropriate when they are away from home
      or someone nearby lacks knowledge of seizure management. Hospitals could provide
      regular group sessions on seizure management for PWE and their significant
      others, in which fears are discussed and evaluated.

PMID- 23159372
TI  - Epigenetic modifications by dietary phytochemicals: implications for personalized
      nutrition.
AB  - In the last two decades, the study of epigenetic modification emerged as one of
      the major areas of cancer treatment targeted by dietary phytochemicals. Recent
      studies with various types of cancers revealed that the epigenetic modifications
      are associated with the food source corresponds to dietary phytochemicals. The
      dietary phytochemicals have been used in Asian countries for thousands of years
      to cure several diseases including cancer. They have been reported to modulate
      the several biological processes including histone modification, DNA methylation
      and non-coding microRNA expression. These events play a vital role in
      carcinogenesis. Various studies suggest that a number of dietary compounds
      present in vegetables, spices and other herbal products have epigenetic targets
      in cancer cells. Dietary phytochemicals have been reported to repair DNA damage
      by enhancing histone acetylation that helps to restrain cell death, and also
      alter DNA methylation. These phytochemicals are able to modulate epigenetic
      modifications and their targets to cure several cancers. Epigenetic aberrations
      dynamically contribute to cancer pathogenesis. Given the individualized traits of
      epigenetic biomarkers, the personalized nutrition will help us to prevent various
      types of cancer. In this review, we will discuss the effect of dietary
      phytochemicals on genetic and epigenetic modifications and how these
      modifications help to prevent various types of cancers and improve health
      outcomes.

PMID- 23159377
TI  - The influence of impression management scales on the Personality Assessment
      Inventory in the epilepsy monitoring unit.
AB  - The Somatic Complaints scale (SOM) and Conversion subscale (SOM-C) of the
      Personality Assessment Inventory perform best in classifying psychogenic non
      epileptic seizures (PNES) from epileptic seizures (ES); however, the impact of
      positive impression management (PIM) and negative impression management (NIM)
      scales on SOM and SOM-C classification has not been examined. We studied 187
      patients from an epilepsy monitoring unit with confirmed PNES or ES. On SOM, the
      best cut score was 72.5 T when PIM was elevated and 69.5 T when there was no
      bias. On SOM-C, when PIM was elevated, the best cut score was 67.5 T and 76.5 T
      when there was no bias. Negative impression management elevations (n=9) were too
      infrequent to analyze separately. Despite similarities in classification
      accuracy, there were differences in sensitivity and specificity with and without
      PIM, impacting positive and negative predictive values. The presence of PIM bias
      generally increases positive predictive power of SOM and SOM-C but decreases
      negative predictive power.

PMID- 23159378
TI  - Neuropsychiatric impairment in children with continuous spikes and waves during
      slow sleep: a long-term follow-up study.
AB  - A long-term follow-up study was conducted in patients affected by Continuous
      Spikes and Waves during slow Sleep (CSWS) to evaluate the long-term outcomes.
      Twenty-five patients (19 males, 6 females), from 2 to 16 years of age (mean age 6
      years+/-3 SD), affected by CSWS syndrome, as defined by the International League
      Against Epilepsy (ILAE, 1989), were enrolled and followed for 11 years (mean
      duration of follow-up: 3.9 years). At the time of the appearance of CSWS, one or
      more neuropsychiatric disorders were present in 96% of the patients, such as
      behavioral problems in 54%, mental retardation in 37.5%, learning disabilities in
      33%, developmental coordination disorder in 17%, language disorder in 12.5%, and
      pervasive developmental disorder in 8%. During the follow-up, neuropsychiatric
      dysfunctions remained unaltered in 52% of the patients, worsened in 24%, and
      improved in only 24%. Our data confirm that CSWS may be associated with a broad
      spectrum of neuropsychiatric disorders and may promote their worsening over time.
      Moreover, the findings cannot be generalized to all cases of children with CSWS
      because most of the children in the subgroups with no change in outcome and worse
      outcome had symptomatic CSWS.

PMID- 23159379
TI  - Seizure exacerbation in two patients with focal epilepsy following marijuana
      cessation.
AB  - While animal models of epilepsy suggest that exogenous cannabinoids may have
      anticonvulsant properties, scant evidence exists for these compounds' efficacy in
      humans. Here, we report on two patients whose focal epilepsy was nearly
      controlled through regular outpatient marijuana use. Both stopped marijuana upon
      admission to our epilepsy monitoring unit (EMU) and developed a dramatic increase
      in seizure frequency documented by video-EEG telemetry. These seizures occurred
      in the absence of other provocative procedures, including changes to
      anticonvulsant medications. We review these cases and discuss mechanisms for the
      potentially anticonvulsant properties of cannabis, based on a review of the
      literature.

PMID- 23159380
TI  - 22q11.2 Microduplication syndrome and epilepsy with continuous spikes and waves
      during sleep (CSWS). A case report and review of the literature.
AB  - Chromosome 22q11.2 microduplication syndrome is characterized by a variable and
      usually mild phenotype and by incomplete penetrance. Neurological features of the
      syndrome may entail intellectual or learning disability, motor delay, and other
      neurodevelopmental disorders. However, seizures or abnormal EEG are reported in a
      few cases. We describe a 6-year-old girl with microduplication of chromosome
      22q11.2 and epilepsy with continuous spikes and waves during sleep (CSWS). Her
      behavioral disorder, characterized by hyperactivity, impulsiveness, attention
      deficit, and aggressiveness, became progressively evident a few months after
      epilepsy onset, suggesting a link with the interictal epileptic activity
      characterizing CSWS. We hypothesize that, at least in some cases, the
      neurodevelopmental deficit seen in the 22q11.2 microduplication syndrome could be
      the consequence of a disorder of cerebral electrogenesis, suggesting the need for
      an EEG recording in affected individuals. Moreover, an array-CGH analysis should
      be performed in all individuals with cryptogenic epilepsy and CSWS.

PMID- 23159381
TI  - Prevalence and characteristics of visual aura in idiopathic generalized epilepsy.
AB  - Some patients with idiopathic/genetic generalized epilepsy (IGE) experience
      visual aura, which can confuse the diagnosis. We sought to determine the
      frequency and characteristics of visual auras in IGE patients. Among the 176 IGE
      patients, 4 men and 7 women reported visual auras (mean age - 24 years).
      Syndromic diagnoses were juvenile myoclonic epilepsy in four, eyelid myoclonia
      with absences (EMA) in three, juvenile absence epilepsy in three, and other in
      one. Visual auras consisted of flashing lights, macropsia, illusional movements,
      and blindness. Eyelid myoclonia with absences was significantly more common in
      the group with visual aura (3 of 11 patients vs. 8 of 165 IGE patients; P=0.02).
      Furthermore, photosensitivity was found significantly more common in IGE patients
      with visual aura (90% vs 46% of the total IGE patients) (P=0.004). In conclusion,
      the visual auras do not exclude a diagnosis of IGE. The presence of visual aura
      in the EMA syndrome is also remarkable.

PMID- 23159382
TI  - Memory in children with temporal lobe epilepsy is at least partially explained by
      executive dysfunction.
AB  - An association between memory and executive dysfunction (ED) has been
      demonstrated in patients with mixed neurological disorders. We aimed to
      investigate the impact of ED in memory tasks of children with temporal lobe
      epilepsy (TLE). We evaluated 36 children with TLE and 28 controls with tests for
      memory, learning, attention, mental flexibility, and mental tracking. Data
      analysis was composed of comparison between patients and controls in memory and
      executive function; correlation between memory and executive function tests; and
      comparison between patients with mild and severe ED in memory tests. Children
      with TLE had worse performance in focused attention, immediate and delayed
      recall, phonological memory, mental tracking, planning, and abstraction.
      Planning, abstraction, and mental tracking were correlated with visual and verbal
      memory. Children with severe ED had worse performance in verbal and visual memory
      and learning tests. This study showed that ED was related to memory performance
      in children with TLE.

PMID- 23159383
TI  - Epilepsy in ring 14 chromosome syndrome.
AB  - Ring chromosome 14 [r(14)] is a rare disorder. The aim of this study was to
      describe two new cases of r(14) drug-resistant epilepsy, and, through an
      extensive review of literature, highlight those epileptological features which
      are more commonly found and which may help in early diagnosis, genetic
      counseling, and treatment. Epilepsy onset in r(14) syndrome takes place during
      the first year of life; seizures are generalized or focal and less frequently
      myoclonic. Seizures might be induced by fever. Focal seizures are characterized
      by staring, eye or head deviation, respiratory arrest, swallowing, and
      hypertonia/hypotonia or clonic movements. Ictal EEG might show both focal and
      diffuse discharges. Interictal EEG reveals mainly focal abnormalities. Mental
      retardation represents a constant feature. Neurological assessment yields a delay
      in motor skill acquisition and less frequently both pyramidal and cerebellar
      signs. Dysmorphic features are evident in the majority of cases. Epilepsy
      associated with r(14) has many features that entail a challenging diagnostic
      process. The reported cases of r(14)-related epilepsy seem to highlight a series
      of common elements which may be helpful in pointing the clinician towards a
      correct diagnosis.

PMID- 23159384
TI  - Psychiatric comorbidity in refractory focal epilepsy: a study of 490 patients.
AB  - We studied the prevalence and associated factors of psychiatric comorbidities in
      490 patients with refractory focal epilepsy. Of these, 198 (40.4%) patients had
      psychiatric comorbidity. An Axis I diagnosis was made in 154 patients (31.4%) and
      an Axis II diagnosis (personality disorder) in another 44 (8.97%) patients. After
      logistic regression, positive family history of psychiatric comorbidities
      (O.R.=1.98; 95% CI=1.10-3.58; p=0.023), the presence of Axis II psychiatric
      comorbidities (O.R.=3.25; 95% CI=1.70-6.22; p<0.0001), and the epileptogenic zone
      located in mesial temporal lobe structures (O.R.=1.94; 95% CI=1.25-3.03; p=0.003)
      remained associated with Axis I psychiatric comorbidities. We concluded that a
      combination of clinical variables and selected structural abnormalities of the
      central nervous system contributes to the development of psychiatric
      comorbidities in patients with focal epilepsy.

PMID- 23159385
TI  - Hypotensive effect of Aspidosperma subincanum Mart. in rats and its mechanism of
      vasorelaxation in isolated arteries.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Aspidosperma subincanum is a medicinal herb that
      is known to be useful for the treatment of cardiovascular-related illnesses.
      However, its effects and pharmacological mechanisms of action have not been
      studied. The aim of the present study was to determine the effect of an ethanol
      extract of Aspidosperma subincanum (EEAS) on blood pressure (in vivo) and
      vascular tension (in vitro) in the rat thoracic aorta. MATERIALS AND METHODS:
      Catheters were inserted into the right femoral vein and artery of anesthetized
      rats for EEAS infusion and the measurement of blood pressure, heart rate and
      aortic blood flow (flow probes were placed around the aorta). Moreover, the
      vasodilator effect of EEAS in isolated pre-contracted rat aortas was examined.
      RESULTS: Intravenous infusion of EEAS resulted in significant and dose-dependent
      hypotension, bradycardia and increased aortic blood flow. In isolated arteries,
      EEAS (0-27 MUg/mL) induced a concentration-dependent relaxation of pre-contracted
      aortic rings; endothelial denudation potentiated this effect. Pre-treatment of
      the aortic rings with ODQ, an inhibitor of soluble guanylyl cyclase (sGC); MDL
      12,330A, an inhibitor of adenylyl cyclase (AC); or CPA, a SERCA inhibitor,
      reduced EEAS-induced vasorelaxation. Treatment with an EEAS impaired contractions
      induced by phenylephrine (an adrenergic agonist) and Bay K 8644 (an L-type Ca(2+)
      channel activator). The blockade of K(+) channels with tetraethylammonium,
      clotrimazole, glibenclamide or 4-aminopyridine reduced the relaxation stimulated
      by EEAS. CONCLUSIONS: These findings suggest that EEAS induces hypotension
      associated with bradycardia. EEAS induces endothelium-independent vascular
      relaxation. The sGC/cGMP and AC/cAMP pathways, SERCA activation and Ca(2+) and
      K(+) flux across the sarcolemma, are likely involved in this relaxation.

PMID- 23159386
TI  - Pluripotent stem cell for modeling neurological diseases.
AB  - The availability of human pluriopotent stem cells, embryonic (ESC) and induced
      pluriopotent (iPSC) stem cells, not only can be a renewable source for
      investigating the early human development, etiology and progression of different
      diseases but also recapitulating the disease with the same genomic materials of
      the patient. In particular, specific neuronal subtypes generated from the patient
      ESC/iPSCs has become a source for studying disease mechanisms underlying
      different neurological disorders and allowed drug discovery. In this review, we
      summarize the recent advances in establishing patient ESC/iPSC to model various
      neurological diseases. We will also discuss the challenges and limitations of the
      current disease models and their potential future applications for untangling the
      unknowns in neurological disorders.

PMID- 23159387
TI  - CD24 expression is associated with progression of gastric cancer.
AB  - BACKGROUND/AIMS: Mortality rates due to gastric cancer are high in Japan. To
      improve patient prognosis, new biomarkers for diagnosis and treatment are
      urgently required. In this study we investigated the role of CD24, a cell
      adhesion glycoprotein implicated in tumor cell proliferation, which is used as a
      prognostic marker in various cancers. METHODOLOGY: We analyzed CD24 expression in
      173 gastric adenocarcinomas by immunohistochemistry and compared the data with
      clinicopathological parameters and patient overall survival. Furthermore, we
      performed Western blotting analysis of CD24 in six human gastric adenocarcinoma
      cell lines, Kato III, MKN1, MKN28, MKN45, MKN74, and HGC-27. RESULTS: CD24 up
      regulation was significantly correlated with depth of invasion (p=0.005) and
      pathological high stages (p=0.043). We observed a relationship between high CD24
      expression and lymph node metastasis, venous invasion and lymphatic invasion.
      CD24 expression tended to be higher in cell lines derived from differentiated
      gastric carcinoma, including those derived from lymph node metastasis.
      CONCLUSIONS: Our study suggests that gastric cancer patients with high CD24
      expression should be closely monitored for recurrence following resections. CD24
      expression is a potential biomarker for gastric cancer prognosis and provides a
      new molecular target for therapeutic strategies.

PMID- 23159388
TI  - Overexpression of p-4ebp1 in Chinese gastric cancer patients and its correlation
      with prognosis.
AB  - BACKGROUND/AIMS: We sought to reveal the status of phosphorylated 4E-binding
      protein 1 (p-4ebp1) expression in Chinese gastric cancer patients and its
      correlation with tumor prognosis. METHODOLOGY: Tissue microarray blocks
      containing gastric cancer tissue and matched noncancerous gastric tissue
      specimens from 286 patients were constructed. The expression of 4E-binding
      protein 1 (4ebp1) and p-4ebp1 of these specimens was analyzed using
      immunohistochemical studies. RESULTS: The expression rates of 4ebp1 and p-4ebp1
      in gastric cancer were 68.5% (196 of 286) and 49.7% (142 of 286) respectively.
      The expression of 4ebp1 was correlated with node metastasis and poor
      differentiation, while the expression of p-4ebp1 was correlated with tumor size,
      node metastasis and TNM stage. p-4ebp1 overexpression has a significant inverse
      correlation with median survival time. CONCLUSIONS: p-4ebp1 expression is
      correlated with later TNM stage and is a prognostic factor of survival time after
      surgery.

PMID- 23159389
TI  - Value of serum procalcitonin levels in predicting spontaneous bacterial
      peritonitis.
AB  - BACKGROUND/AIMS: Spontaneous bacterial peritonitis (SBP) is a life-threatening
      disease that poses a great diagnostic challenge to clinicians. We aimed to
      systemically and quantitatively summarize the current evidence on the diagnostic
      value of the procalcitonin (PCT) test in identifying SBP. METHODOLOGY: We
      searched EMBASE, MEDLINE, the Cochrane database and reference lists of relevant
      articles with no language restrictions through May 2012. We selected original
      research that reported the diagnostic performance of PCT alone or compared with
      other biomarkers to diagnose SBP. We summarized test performance characteristics
      using forest plots, summary receiver operating characteristic curves and
      bivariate random effects models. RESULTS: We found only three qualifying studies
      examining 181 episodes of suspected infection with 50 (27.6%) confirmed SBP
      episodes from 3 countries. Bivariate pooled sensitivity, specificity, positive
      likelihood ratios and negative likelihood ratios were 86% (95%CI: 73%-94%), 80%
      (95%CI: 72%-87%), 7.73 (95%CI: 0.91-65.64) and 0.14 (95%CI: 0.01-1.89),
      respectively. The global measures of accuracy, area under the receiver operating
      curve (AUROC) and diagnostic odds ratio (DOR), showed PCT has excellent
      discriminative capability and individual study showed serum PCT testing has
      better accuracy than ascitic PCT, serum CRP or IL-6 testing. There was evidence
      of significant heterogeneity but no evidence of publication bias. CONCLUSIONS:
      The existing literature suggests moderate to high accuracy for PCT as a
      diagnostic aid for SBP. However, larger, appropriately designed prospective
      studies are needed to conclusively address the value of serum PCT testing in SBP
      diagnosis.

PMID- 23159391
TI  - Primary small bowel malignancy: a 10-year clinical experience from Southern
      Taiwan.
AB  - BACKGROUND/AIMS: The difficulty in establishing early definitive diagnosis and
      treatment of primary small bowel malignancy (PSBM) is a challenge for clinicians.
      This study aimed to analyze the symptomatology, diagnosis and outcomes of PSBM.
      METHODOLOGY: A retrospective chart review study was conducted on 49 patients who
      underwent surgical treatment for PSBM at a tertiary hospital between May 2000 and
      January 2010. RESULTS: The patients with PSBM had non-specific clinical symptoms.
      Major diagnostic tools in the current study were computed tomography (CT) (n=40),
      gastrointestinal series radiography (n=10), angiography (n=5), double-balloon
      enteroscopy (n=3), gastroduodenoscopy (n=2), magnetic resonance imaging (n=1) and
      exploratory laparotomy (n=8). Gastrointestinal stromal tumor (GIST) was the most
      common PSBM (n=21), followed by lymphoma (n=14), adenocarcinoma (n=8),
      leiomyosarcoma (n=3) and sarcoma (n=3). The overall 5-year cumulative survival
      rate of the patients with PSBM was 57.1% with a mean survival time of 31.8+/-7.8
      months. The 5-year cumulative survival rates for the different PSBMs were 79.1%,
      46.9% and 33.2% for GIST, adenocarcinomas and lymphomas, respectively (p=0.087).
      CONCLUSIONS: CT is very useful in detecting PSBM. Poor prognosis in PSBM patients
      detected by CT or angiography could be the result of delayed diagnosis prior to
      the procedure.

PMID- 23159390
TI  - Tumor size as a prognostic factor in patients with node-negative gastric cancer
      invading the muscularis propria and subserosa (pT2-3N0M0 stage).
AB  - BACKGROUND/AIMS: To explore the impact of tumor size on outcomes in patients with
      pT2-3N0M0 stage. METHODOLOGY: ROC curve analysis was used to determine the
      appropriate cut-off value for tumor size in 115 patients of pT2-3N0M0 stage
      gastric cancer. Based on this cut-off value, patients were divided into two
      groups. The five-year overall survival (OS) rates in the two groups were compared
      according to the independent prognostic factors. RESULTS: Using this cut-off
      value of 3.7cm, 62 patients had large-sized tumors (LSTs, tumor size >3.7cm) and
      53 had small-sized tumors (SSTs, tumor size <3.7cm). Patients with LSTs had a
      significantly lower five-year OS rate than those with SSTs (60.7% vs. 88.4%,
      p=0.000). Depth of tumor invasion, histological type and tumor size were
      independent prognostic factors. In patients with pT2N0M0 stage tumors or pT2
      3N0M0 stage patients with undifferentiated type tumors, five-year OS rates were
      significantly lower for LSTs than for SSTs (p<0.05 each). CONCLUSIONS: Tumor size
      is a prognostic factor in patients with pT2-3N0M0 stage. Especially for pT2N0M0
      stage gastric cancer and pT2-3N0M0 stage gastric cancer with undifferentiated
      type tumors, the prognosis was poorer in patients with tumor size >3.7cm than
      that in patients with tumor size <3.7cm.

PMID- 23159392
TI  - Staging laparoscopy in advanced gastric cancer: usefulness and issues requiring
      improvement.
AB  - BACKGROUND/AIMS: We performed staging laparoscopy (SL) for advanced gastric
      cancer with suspicion of positive peritoneal cytology (CY) or peritoneal
      metastasis (P). This study was designed to show SL's utility in advanced gastric
      cancer. METHODOLOGY: This was a retrospective study of 124 patients with primary
      gastric cancer who underwent SL between October 2001 and March 2009. RESULTS:
      There were no perioperative complications without a case of bleeding. The patient
      breakdown was P0CY0, 67; P0CY1, 19; P1CY0, 6; and P1CY1, 32. Chemotherapy was
      administered as the initial treatment in 33 patients and the period from SL to
      chemotherapy was 19.5 days. In 7 patients undergoing laparotomy as the initial
      treatment but later requiring exploratory laparotomy or palliative surgery
      followed by chemotherapy, the period from laparotomy to chemotherapy was 36.8
      days. The difference was significant (p<0.0001). P1 was confirmed in 10 (14.5%)
      of 69 patients undergoing laparotomy as the initial treatment. CY was re-examined
      in 53 of these 69 patients and CY1 was confirmed in 6 (13.3%) of 45 patients who
      were CY0 according to SL. CONCLUSION: With SL, early initiation of chemotherapy
      was possible for P1 patients. Although improved accuracy is required, SL, which
      can be carried out safely with minimal invasiveness, was suggested to be useful.

PMID- 23159393
TI  - Transanal endoscopic microsurgery versus laparoscopic lower anterior resection
      for the treatment of T1-2 rectal cancers.
AB  - BACKGROUND/AIMS: It remains unknown whether transanal endoscopic microsurgery
      (TEMS) is superior to laparoscopic lower anterior resection (LAR) for the
      treatment of rectal cancer. This study aimed to compare the surgical and
      oncological effectiveness as well as safety of TEMS and LAR in T1-2 rectal cancer
      patients. METHODOLOGY: T1-2N0 rectal cancer patients were prospectively and
      randomly assigned to local excision using TEMS (n=30) or radical resection using
      LAR (n=30). The primary outcome measures were postoperative recovery course.
      RESULTS: The operative duration of TEMS was significantly shorter than that of
      LAR (130.3+/-16.7 minutes vs. 198.7+/-16.8 minutes, p<0.01). The TEMS group
      restarted bowel movement significantly earlier than the LAR group (51.4+/-5.4h
      vs. 86.2+/-8.7h, p<0.01). The postoperative complications were mild and self
      limited in the 2 groups. Local recurrences occurred in 2 T2 patients (2/28, 7.1%)
      at 8 months and 16 months following TEMS, respectively; no patient (0/30, 0.0%)
      developed local recurrence following LAR. CONCLUSIONS: TEMS was associated with
      more rapid postoperative recovery and minimal surgical morbidity in T1-2 rectal
      cancer patients as compared to LAR.

PMID- 23159394
TI  - Peritoneal access, transgastric peritoneoscopy and oophorectomy - feasibility
      study on an experimental Swine model.
AB  - BACKGROUND/AIMS: Natural orifice translumenal endoscopic surgery (NOTES) still
      poses numerous challenges, even in cases of relatively simple surgical
      procedures. This study aims to assess the feasibility of transgastric resectional
      interventions using commonly available endoscopic equipment as well as to offer a
      safe closure method of the gastric access site. METHODOLOGY: Ten pigs underwent
      pure transgastric endoscopic oophorectomy using a single channel endoscope. The
      gastric defect was closed using over-the-scope clips (OTSCTM, OVESCO Endoscopy).
      After 2 weeks the animals underwent autopsies. RESULTS: All procedures were
      successful. Transgastric access time varied from 4.46 to 33.24 minutes. The
      peritoneal exploration took 31 minutes and oophorectomy needed in average of 21
      minutes (range 15-28 minutes). The animals for which the gastric access site was
      closed with OTSCTM survived for 2 weeks without complications. CONCLUSION: This
      study demonstrates the technical feasibility and safety of pure transgastric
      endoscopic oophorectomy using conventional endoscopic instrumentation in a
      porcine model. OTSCTM closure system is an easy to use and reliable gastric
      closure method.

PMID- 23159395
TI  - The automated micronucleus assay for early assessment of genotoxicity in drug
      discovery.
AB  - Recent publications on the automated in vitro micronucleus assay show predictive
      values higher than 85% for the classification of in vitro aneugens, clastogens
      and non-genotoxic compounds. In the present work, the CHO-k1 micronucleus assay
      in combination with cellular imaging was further evaluated. Firstly, the effect
      of a range of S9 concentrations on micronucleus formation and cytotoxicity was
      investigated. Subsequently, the reproducibility and predictivity of the
      micronucleus assay on CHO-k1 cells was investigated with a set of four compounds.
      Then, a larger set of compounds (n=44) was tested on CHO-k1 cells and inter
      laboratory correlation was calculated. Finally, cellular imaging was compared
      with flow cytometry for in vivo assessment of micronucleus formation. The
      concentration of S9 had a significant impact on micronucleus formation and
      cytotoxicity. In addition, calculations of relative cell count (RCC) and
      cytokinesis-block proliferation index (CBPI) showed to be complementary to
      cytotoxicity assessment. The CHO-k1 micronucleus assay correctly classified the
      four reference compounds, with a dose-response relationship and low variability.
      Based on a larger set of compounds, the assay proved to be reliable with a
      sensitivity of 94% (n=31) and a specificity of 85% (n=13). A correlation
      coefficient of 97% was obtained when the lowest observable adverse effect levels
      (LOAELs) from our study were compared with those published by Diaz et al. (2007)
      [10]. In conclusion, the in vitro CHO-k1 micronucleus assay combined with
      cellular imaging is a predictive assay appropriate for genotoxicity screening at
      early stages of drug development. In addition, for in vivo assessment of
      micronucleus formation, we preferred to use flow cytometry rather than cell
      imaging.

PMID- 23159396
TI  - High resolution fluorescence microscopy evidence on the transport of
      immunoglobulins. Differences between mammalian IgG, F(ab')2 and avian IgY.
AB  - We describe the subcellular localization of horse F(ab')(2) and IgG, and ostrich
      IgY labeled with fluorescein isothiocyanate (FITC) administered IV to mice. We
      used wide field high sensitivity fluorescence microscopy deblurred by 3
      dimensional blind deconvolution of kidney, liver, lungs and brain sections.
      Sections were obtained from mice sacrificed 15 min, 1 or 5 h after receiving FITC
      immunoproteins, counter-stained with DAPI (4',6'-diamidino-2-phenylindole) and
      Evans blue. FITC-IgG and its fractions are rapidly taken up and extravasated by
      vascular endothelium. FITC-IgG and FITC-F(ab')(2) appear to be quickly secreted
      by glomeruli endothelium and to be reabsorbed along all nephron segments. FITC
      IgG and FITC-F(ab')(2) appeared 15 min after IV injection within bronchial,
      alveolar and bile duct epithelium. Hepatocytes were loaded with fluorescence
      after 15 min of administration. Fluorescence was absent from brain slices, except
      for the endothelium of some vessels in brain ventricles which appeared intensely
      fluorescent. Fluorescence appeared in intracellular vesicles which conferred the
      tissues a glowing foamy aspect for up to 5 h after inoculation. Arterial elastic
      layers were intensely green after horse FITC-Ig inoculation. Ostrich FITC-IgY
      behaved completely differently to horse Ig's; only 1 h after injection it was
      possible to observe small brightly green scarce vesicles in vascular endothelium
      of arteries, interstitial kidney capillaries between nephron tubules and were
      also scarce in glomeruli endothelium; FITC-IgY appeared only in hepatic sinusoids
      in the liver. No IgY was seen in bronchial and alveolar endothelium, in bile
      ducts or in hepatocytes.

PMID- 23159397
TI  - Systemic effects induced by the venom of the snake Bothrops caribbaeus in a
      murine model.
AB  - Snakebite envenoming by Bothrops caribbaeus, an endemic viperid from the Lesser
      Antillean island of Saint Lucia, is clinically characterized by local tissue
      damage and systemic thrombosis that can lead to cerebral, myocardial or pulmonary
      infarctions and venous thromboses. Systemic effects (lethality, pulmonary
      hemorrhage, thrombocytopenia and coagulopathy) induced by intravenous (i.v.)
      administration of B. caribbaeus venom were studied in mice. The role of snake
      venom metalloproteinases (SVMPs) in these systemic alterations was assessed by
      inhibition with the chelating agent calcium disodium ethylenediaminetetraacetic
      acid (CaNa(2)EDTA). A snake C-type lectin-like (snaclec) and a type P-III
      hemorrhagic SVMP were isolated and characterized from this venom, and the effect
      of venom and the isolated snaclec on human platelet aggregation was studied in
      vitro. Results indicate that SVMPs play an important role in the overall toxicity
      of B. caribbaeus venom, being responsible for systemic hemorrhage and lethality,
      but not thrombocytopenia, whereas the isolated snaclec is involved in the
      thrombocytopenic effect. Both venom and snaclec induce platelet
      aggregation/agglutination. Moreover, the snaclec binds directly to glycoprotein
      Ib (GPIb) and induces agglutination in washed fixed platelets. On the other hand,
      B. caribbaeus venom hydrolyzed fibrinogen in vitro and induced a partial drop of
      fibrinogen levels with an increase in fibrin/fibrinogen degradation products
      (FDP) levels in vivo. The negative result for D-dimer (DD) in plasma is
      consistent with the lack of microscopic evidence of pulmonary thrombosis and
      endothelial cell damage. Likewise, no increments in plasma sE-selectin levels
      were detected. The absence of thrombosis in this murine model suggests that this
      effect may be species-specific.

PMID- 23159399
TI  - An efficient analytical platform for on-line microfluidic profiling of
      neuroactive snake venoms towards nicotinic receptor affinity.
AB  - Venomous snakes have evolved their efficient venomous arsenals mainly to
      immobilize prey. The highly variable toxic peptides in these venoms target a
      myriad of neurotoxic and haemotoxic receptors and enzymes and comprise highly
      interesting candidates for drug discovery. Discovery of bioactive compounds from
      snake venoms, however, is a challenge to achieve. We have developed and applied a
      methodology to rapidly assess bioactives in a snake venom proteome. Our
      microfluidic platform opens up efficient and rapid profiling of venomous anti
      cholinergic receptor compounds. The key advantages of our methodology are: (i)
      nano amounts of venom needed; and (ii) a direct correlation of selected
      bioaffinities with accurate mass. To achieve this, we have for the first time
      successfully constructed a functional post nano-LC split to MS and bioaffinity
      profiling. In our method, comprehensive venom profiles with accurate masses and
      corresponding bioaffinities are obtained in one analytical run and will
      subsequently allow immediate purification of bioactive peptides with LC-MS,
      guided by accurate masses of the bioactives only. We profiled several neurotoxic
      Elapidae snake venoms using our methodology in combination with the acetylcholine
      binding protein (AChBP) as biological target protein. The latter is a homologue
      of nicotinic acetylcholine receptors (nAChRs), a drug target in neurodegenerative
      diseases and cognitive decline such as Parkinson's and Alzheimer's, and in pain
      related diseases. Our methodology was evaluated and validated with high-affinity
      alpha-bungarotoxin and haemotoxic/proteolytic Vipera ammodytes venom spiked with
      alpha-bungarotoxin. Thereafter, the methodology was applied to profile the venom
      proteomes of Dendroaspis jamesoni kaimosae, Naja annulifera and Naja nivea.
      Gathering comprehensive profiling data took less than 2 h per snake venom
      measured. The data yielded 20 AChBP ligands of which the corresponding accurate
      masses were used to retrieve information from literature regarding their function
      and targeting specificity. We found that from these 20 ligands, 11 were
      previously reported on, while information on the others could not be found. From
      these 11 peptides, five have been reported to have nAChR affinity, while the
      others are reported as cytotoxic, cardiotoxic or as orphan toxin. Our methodology
      has the potential to aid the field of profiling complex animal venoms for drug
      discovery.

PMID- 23159398
TI  - Ultra-fast analysis of anatoxin-A using laser diode thermal desorption
      atmospheric pressure chemical ionization-tandem mass spectrometry: validation and
      resolution from phenylalanine.
AB  - A novel approach for the analysis of the cyanobacterial toxin, anatoxin-a (ANA
      a), in an environmentally relevant matrix, using laser diode thermal desorption
      atmospheric pressure chemical ionization-tandem mass spectrometry (LDTD-APCI
      MS/MS) is presented. The ultra-fast analysis time (15 s/sample) provided by the
      LDTD-APCI interface is strengthened by its ability to remove interference from
      phenylalanine (PHE), an isobaric interference in ANA-a analysis by MS/MS. Thus
      the LDTD-APCI interface avoids the time consuming steps of derivatization,
      chromatographic separation or solid-phase extraction prior to analysis. Method
      development and instrumental parameter optimizations were focused toward signal
      enhancement of ANA-a, and signal removal of a PHE interference as high as 500
      MUg/L. External calibration in a complex matrix gave detection and quantification
      limit values of 1 and 3 MUg/L respectively, as well as good linearity (R(2) >
      0.999) over nearly two orders of magnitude. Internal calibration with clomiphene
      (CLO) is possible and method performance was similar to that obtained by external
      calibration. This work demonstrated the utility of the LDTD-APCI source for ultra
      fast detection and quantification of ANA-a in environmental aqueous matrices, and
      confirmed its ability to suppress the interference of PHE without sample
      preparation or chromatographic separation.

PMID- 23159401
TI  - Imaging features of intrahepatic cholangiocarcinoma in Gd-EOB-DTPA-enhanced MRI.
AB  - OBJECTIVE: The aim of this study is to describe the imaging features of
      intrahepatic cholangiocarcinoma in Gd-EOB-DTPA-enhanced MRI and to determine
      whether it results in improved tumour conspicuity of cholangiocarcinoma.
      MATERIALS AND METHODS: Fifty-four patients with histologically proven
      intrahepatic cholangiocarcinoma underwent MRI of the liver using a 1.5T MR
      scanner with Gadoxetic acid disodium (Gd-EOB-DTPA; Eovist/Primovist, Bayer
      Healthcare, Berlin, Germany). The standard imaging protocol included a T2w multi
      shot TSE sequence with fat saturation (fs), a T2w single shot sequence without fs
      and a T1w 3D GRE sequences with fs (unenhanced and arterial, portovenous, late
      venous and hepatobiliary phase). Two board certified radiologists experienced in
      liver MRI (5 and 10 years experience) evaluated retrospectively all MRI scans
      qualitatively and quantitatively. Signal was measured with region-of-interests
      (ROI) and signal-to-noise (SNR) as well as contrast-to-noise (CNR) was
      calculated. Statistical significance was tested with an ANOVA and a pairwise
      Wilcoxon rank test. RESULTS: All intrahepatic cholangiocarcinomas presented as
      hypointense lesions in the late venous and hepatobiliary phase. Images in the
      hepatobiliary phase showed the highest lesion conspicuity, i.e. n=9 blurred
      (16.6%), n=31 moderate (57.4%) and n=14 sharp (26%). This was significantly
      higher than the lesion conspicuity of all other sequences or phases. Furthermore,
      the CNR was the highest in this sequence with 76.8+/-51.3, with significantly
      higher values than the CNR of the unenhanced T1w sequence (CNR: 35.6+/-21.0;
      p<0.0001) and the arterial phase images (CNR: 53.6+/-36.8; p<0.001). The
      hepatobiliary phase images showed a SNR of 97.3+/-59.7 (p<0.001) and thus was
      significantly different from the unenhanced T1w sequence (SNR: 60.4+/-35.3;
      p<0.001), whereas the increase in SNR from the late venous to hepatobiliary phase
      was neglectable, indicating that no liver-specific contrast uptake is present in
      cholangiocarcinoma. CONCLUSION: Intrahepatic cholangiocarcinoma presents as a
      hypointense lesion in Gd-EOB-DTPA-enhanced MRI in late venous phase images. The
      lesion conspicuity as well as CNR was highest in the hepatobiliary phase.
      Consequently, hepatobiliary phase images in Gd-EOB-DTPA-enhanced MRI images might
      be helpful for therapy planning due to the exact depiction of the tumour borders.

PMID- 23159400
TI  - The identification and characterization of epitopes in the 30-34 kDa Trypanosoma
      cruzi proteins recognized by antibodies in the serum samples of chagasic
      patients.
AB  - Trypanosoma cruzi proteins with molecular weight between 30 and 34 kDa have shown
      high reactivity in western blot assays with serum samples from chagasic
      individuals. However, in-depth analysis of the constituents of these protein
      fractions has not been performed. This is the first report of an immunoaffinity
      proteomic approach to identify the immunodominant 30-34 kDa proteins of T. cruzi
      that could eventually be used for the diagnosis of Chagas disease. We used two
      different sample preparation protocols for protein digestion coupled to mass
      spectrometry to identify proteins in the protein fraction. The immunodominant
      proteins and their respective epitopes were then identified by co
      immunoprecipitation and excision-epitope mapping/mass spectrometry, using human
      sera followed by the prediction and three-dimensional structural modeling of
      reactive epitopes. The use of different sample preparation methods allowed the
      identification of a relatively high number of proteins, some of which were only
      identified after one or multiple sample preparation and digestion protocols.
      Seven immunodominant proteins were identified by co-immunoprecipitation with
      purified IgGs from chagasic serum samples. Moreover, six reactive peptide
      epitopes were detected in four of these proteins by excision-epitope mapping/mass
      spectrometry. Three-dimensional structural models were obtained for the
      immunoreactive peptides, which correlated well with the linear B-cell epitope
      prediction tools.

PMID- 23159402
TI  - Symptomatic nonfunctioning parathyroid cysts: role of simple aspiration and
      ethanol ablation.
AB  - OBJECTIVES: To evaluate the outcomes of simple aspiration and ethanol ablation in
      the management of symptomatic nonfunctioning parathyroid cyst (PC). METHODS: We
      performed simple aspirations for 12 PCs in 12 patients from March 1997 to June
      2010. PC was diagnosed if the aspirated fluid was clear colorless and showed an
      elevated parathyroid hormone (PTH) level. Ethanol ablation (EA) was performed for
      recurrent PCs. Simple aspirations were performed using 23-gauge needles and EAs
      using 18-gauge needles with 99% ethanol under ultrasound (US) guidance. We
      evaluated cyst volume, cosmetic score, symptom score, and complications. RESULTS:
      Mean follow-up period of all patients was 19.2 +/- 12.9 months (median, 15.0
      months; range, 7-40 months). Simple aspiration was successful in four patients,
      and the mean volume reduction after simple aspiration was 98.2 +/- 3.5% (range,
      92.9-100%). In eight recurrent cases, EA resulted in a significant decrease in
      volume (P=0.012), as well as in cosmetic (P=0.011) and symptom (P=0.01) scores at
      last follow-up; however two cases of primary failure of EA was treated by repeat
      EA. No major complications occurred in any patient. CONCLUSIONS: For symptomatic
      nonfunctioning PCs, simple aspiration could be a first line procedure for
      diagnosis and treatment, while EA can be a subsequent treatment modality for
      recurrent cases.

PMID- 23159403
TI  - Power and pulsed Doppler evaluation of ovarian hemodynamic changes during
      diestrus in pregnant and nonpregnant bitches.
AB  - The aim of the study was to further characterize the relationship between
      hemodynamic changes in the ovary and luteal function in pregnant and nonpregnant
      bitches. Fourteen German Shepherd bitches were monitored three times a week from
      the first day of cytological diestrus (D1) until parturition or the end of
      diestrus (progesterone <2 ng/mL) by color Doppler, pulsed wave spectral Doppler,
      and power Doppler (PD) ultrasonography. By means of PD the total number of color
      pixels were calculated. The Doppler parameters evaluated were: peak systolic
      velocity (PSV), end diastolic velocity (EDV), and both resistive and pulsatility
      indices. Blood samples were collected three times a week throughout the
      experiment to determine progesterone (P4) concentrations. The length of diestrus
      in pregnant versus nonpregnant group was significantly shorter (P < 0.01; 57 +/-
      1 vs. 63 +/- 1, respectively). By means of pulsed wave spectral Doppler the
      waveform showed a typical pattern of a low-resistive vessel characterized by a
      rapid systolic peak followed by a slow telediastolic decrease with a relatively
      high end-diastolic velocity. Blood flow parameters did not differ between left
      and right ovary. In both groups PSV and EDV showed a gradual decrease with the
      progress of diestrus; however, the values of PSV and EDV were significantly
      higher (P < 0.05) in the pregnant group versus nonpregnant group from D31 to D61
      and from D49 to D58 respectively. Moreover, a significantly decrease (P < 0.05)
      of PSV and EDV in the pregnant group was observed from D46 to D58 and from D49 to
      D55, respectively. The resistive and pulsatility indices showed an increase
      during diestrus and the values were significantly lower (P < 0.05) in the
      pregnant group from D49 to D61. By means of PD, the pixel number was
      significantly higher (P < 0.05) in the pregnant versus nonpregnant group from D40
      to D61. In particular, a significant decrease (P < 0.05) in the pixel number in
      the pregnant group was observed from D46 to D61. The comparison of the P4 values
      with the ovarian pixel number in the pregnant and nonpregnant group showed a
      direct correlation (r = 0.792, N = 59 and r = 0.774, N = 59, respectively). In
      particular, the P4 values were higher (P < 0.05) in the pregnant than in the
      nonpregnant group from D37 to D52. In conclusion, significant physiological
      differences between pregnant and nonpregnant bitches in terms of P4 and ovarian
      blood supply are reported. In addition it was possible to define that blood flow
      pattern during diestrus in pregnant bitches is not always closely related with P4
      production.

PMID- 23159404
TI  - Analysis of nuclear localization of interleukin-1 family cytokines by flow
      cytometry.
AB  - The dual function cytokines IL-1alpha, IL-33 and IL-37 are members of the IL-1
      cytokine family. Besides of being able to bind to their cognate receptors on
      target cells, they can act intracellularly in the producing cell. All three are
      able to translocate to the nucleus and have been discussed to affect gene
      expression. In order to compare and quantitate nuclear translocation of these IL
      1 family members we established a robust technique which enables to measure
      nuclear localization on a single cell level by flow cytometry. Vectors encoding
      fusion proteins of different IL-1 family members with enhanced green fluorescent
      protein were cloned and cell lines transiently transfected with these.
      Fluorescent fusion proteins in intact cells or in isolated nuclei were detected
      subsequently by fluorescence microscopy and flow cytometry, respectively.
      Depending on the cellular system, cells and nuclei were distinguishable by flow
      cytometry in forward scatter/sideward scatter. Fluorescent fusion proteins were
      detectable in isolated nuclei up to three days following preparation. Signal
      intensity of fusion proteins of IL-33 and IL-37 in isolated nuclei but not of IL
      1alpha, was markedly increased by fixation with paraformaldehyde, directly
      following cell lysis, indicating that IL-1alpha binds stronger to nuclear
      structures than IL-33 and IL-37. Nuclear translocation of fluorescent IL-37
      fusion proteins in a stably transfected RAW264.7 mouse macrophage cell line
      required stimulation with lipopolysaccharide. Applying this method we
      demonstrated that a prolonged lag phase of more than 15h before LPS-stimulated
      nuclear translocation was detected. In summary, we present a robust method to
      analyze and quantitate nuclear localization of IL-1 cytokine family members.

PMID- 23159405
TI  - Differential regulation of M3/6 (DUSP8) signaling complexes in response to
      arsenite-induced oxidative stress.
AB  - Mitogen-activated protein kinase (MAPK) cascades are involved in the regulation
      of cellular proliferation, differentiation, survival, apoptosis, as well as in
      inflammatory responses. Signal intensity and duration have been recognized as
      crucial parameters determining MAPK signaling output. Phosphatases play a
      particularly important role in this respect, by tightly controlling MAPK
      phosphorylation and activation. M3/6 (DUSP8) is a dual-specificity phosphatase
      implicated in the dephosphorylation and inactivation of JNK and, to a lesser
      extent, p38 MAPKs and is found in a complex with these kinases, along with other
      pathway components, held together by scaffold proteins. The JNK family consists
      of three genes, giving rise to at least ten different splice variants. Some
      functional differences between these gene products have been demonstrated, but
      the underlying molecular mechanisms and the roles of individual splice variants
      are still incompletely understood. We have investigated the interaction of M3/6
      with JNK isoforms, as well as scaffold proteins of the JNK interacting protein
      (JIP) family, in order to elucidate the contribution of M3/6 to the regulation of
      distinct JNK signaling modules. M3/6 exhibited stronger binding towards JNK1beta
      and JNK2alpha isoforms and this was reflected in higher enzymatic activity
      towards JNK2alpha2 when compared to JNK1alpha1 in vitro. After activation of the
      pathway by exposure of cells to arsenite, the interaction of M3/6 with JNK1alpha
      and JNK3 was enhanced, whereas that with JNK1beta or JNK2alpha decreased. The
      modulation of binding affinities was found to be independent of JNK-mediated M3/6
      phosphorylation. Furthermore, arsenite treatment resulted in an inducible
      recruitment of M3/6 to JNK-interacting protein 3 (JIP3) scaffold complexes, while
      its interaction with JIP1 or JIP2 was constitutive. The presented data suggest an
      isoform-specific role for the M3/6 phosphatase and the dynamic targeting of M3/6
      towards distinct JNK-containing signaling complexes.

PMID- 23159406
TI  - Comparison of tissue characteristic between left main and non-left main coronary
      artery lesions--assessment using integrated backscatter intravascular ultrasound.

PMID- 23159407
TI  - Impaired arm development after Blalock-Taussig shunts in adults with repaired
      tetralogy of Fallot.
AB  - BACKGROUND: Many adults with repaired tetralogy of Fallot have had prior Blalock
      Taussig shunts. These shunts may theoretically hinder growth and development of
      the ipsilateral arm. METHODS: We prospectively enrolled consecutive patients with
      tetralogy of Fallot in a cross-sectional study to measure arm length and assess
      handgrip strength. Bilateral handgrip strength was quantified by a dynamometer in
      a standing position after instructing patients to clench each hand tightly in
      succession. The maximum force achieved, in kilograms, was measured. RESULTS: A
      total of 80 consecutive adults with tetralogy of Fallot, aged 36.0 +/- 12.5
      years, 49% female, were prospectively enrolled. Thirty-eight (47.5%) patients had
      prior Blalock-Taussig shunts at a median age of 1.0 year. Twenty-one (55.3%) were
      left-sided and 23 (60.5%) were classic shunts. All but six patients with right
      sided shunts and one without a prior shunt were right-handed. The shunts were
      present for a median of 4.0 years prior to takedown during corrective surgery.
      The arm ipsilateral to the shunt was significantly shorter than the contralateral
      arm (71.5 +/- 6.1 versus 73.6 +/- 5.6 cm, P<0.0001). Handgrip strength was
      significantly weaker on the ipsilateral versus contralateral side (median [IQR],
      26.5 [14.0-41.5] versus 31.0 [18.0-46.0] kg, P<0.0001) and the ipsilateral-to
      contralateral handgrip ratio was lower with classic versus modified shunts
      (median [IQR], 1.05 [1.02-1.14] versus 1.19 [1.07-1.33] kg, P=0.0541).
      CONCLUSION: In patients with tetralogy of Fallot, Blalock-Taussig shunts may
      impair normal development of the ipsilateral arm with repercussions in adulthood
      that include shorter limb length and reduced handgrip strength. These changes are
      most pronounced in patients with classic end-to-side anastomoses.

PMID- 23159408
TI  - Transvenous cardioverter-defibrillator lead implantation in a patient with three
      mechanical prosthetic valves: all in one solution.

PMID- 23159409
TI  - Women hospitalized with atrial fibrillation: gender differences, trends and
      outcome from a 20-year registry in a Middle Eastern country (1991-2010).
AB  - BACKGROUND: Most of the published research on atrial fibrillation (AF) is limited
      to studies in the developed world and included mainly Caucasian patients. Data
      about women with AF among other ethnicities is very limited. OBJECTIVES: The aim
      of this study was to compare the clinical characteristics, treatment and outcome
      of women to men hospitalized with AF in a middle-eastern country. METHODS:
      Retrospective analysis of prospective registry of all patients hospitalized with
      AF in Qatar from 1991 through 2010 was made. Clinical characteristics,
      management, and outcomes of AF patients were compared according to gender.
      RESULTS: During the 20-years period; 1417 women and 2432 men were hospitalized
      for AF. Women were 5 years older and more likely to have diabetes mellitus,
      hypertension, and chronic renal impairment and were also less likely to be
      current smokers and to have ischemic heart disease and impaired left ventricular
      function when compared to men. There was no gender preference in the use of
      anticoagulation. The prevalence of concomitant ischemic heart disease and
      hypertension increased, while the prevalence of valvular heart disease and heart
      failure decreased among patients hospitalized with AF over the study period. In
      hospital mortality and stroke rates were comparable between the two groups.
      CONCLUSIONS: Women hospitalized with atrial fibrillation were older in age and
      had higher prevalence of co-morbid cardiovascular risk factors compared to men
      whereas, mortality and stroke rates were comparable.

PMID- 23159410
TI  - Feasibility limits of transradial primary percutaneous coronary intervention in
      acute myocardial infarction in the real life (TRAP-AMI).
AB  - BACKGROUND: There is growing evidence that transradial (TRI) as compared to
      transfemoral (TFI) percutaneous coronary intervention (PCI) is associated with
      improved clinical outcome driven by less hemorrhagic complications, in particular
      in STEMI patients receiving aggressive antithrombotic treatment. Feasibility rate
      of TRI in STEMI patients has not yet been evaluated. METHODS/RESULTS: Four
      hundred seventy-five consecutive STEMI patients (<12h) without cardiogenic shock
      were prospectively screened for this all-comer single-centre registry between
      January 2008 and August 2010. Nine patients were excluded for a priori
      ineligibility for TRI (forearm shunt for dialysis, prior TRI failure). In the 466
      patients enrolled, the operator's opinion about ease of radial puncture was
      assessed in 4 categories, based on radial pulse quality. Operators were advised
      not to attempt TRI if ease of puncture was judged "probably
      difficult/impossible". In case of puncture failure the operator switched
      immediately to TFI. The mean age of patients was 61 +/- 14 (range 27-94) years.
      Seventy-three percent were men, 17% had diabetes. Nine percent had previous PCI.
      Glycoprotein inhibitors were used in 70%, and thrombectomy was performed in 70%
      of patients. PCI was performed using 6F and 5F guiding catheters. Procedural
      success rate was 98.2% (TIMI flow >= 2). In 4.1% (n=19) of patients the operator
      judged ease of radial puncture "probably difficult/impossible" and no TRI attempt
      was performed (primary TFI). In the 447 patients with TRI attempt, TRI failure
      requiring switch to TFI (secondary TFI) was necessary in 22 patients (4.7% of
      total) following radial puncture failure (n=15), dissection of the radial artery
      (n=1), prohibitive tortuosities or stenosis of the upper limb axis (n=2), or non
      selective position or lack of stability of the guiding catheter (n=2). After the
      start of the angioplasty procedure, switch from TR to TF was not necessary in any
      patient. In total, the overall feasibility rate of TRI was 91.2%. Independent
      predictors of final TFI were age >= 80 years (adjusted OR: 2.37; 95% CI:1.05
      5.34, p=0.037), body weight<60 kg (adjusted OR: 2.84; 95% CI:1.22-6.59, p=0.015);
      and previous PCI (adjusted OR: 3.42; 95% CI:1.40-8.37, p=0.007); female gender
      was borderline significant (adjusted OR:2.10; 95% CI:0.97-4.54, p=0.059).
      CONCLUSION: In STEMI patients without cardiogenic shock and without a priori
      indication for TFI, PCI can be performed via the radial artery in more than 90%
      of cases with high procedural success rate. Operator's judgement of eligibility
      for TRI based on radial pulse quality is predictive of successful TRI in 95% of
      cases. TR failure is significantly more common in the elderly and in patients
      with low body weight.

PMID- 23159411
TI  - Potentially important considerations in choosing specific statin treatments to
      reduce overall morbidity and mortality.
AB  - Hypercholesterolemia and dyslipidemia are independent risk factors for
      cardiovascular disease and death. Statins are the drugs of choice to decrease
      plasma cholesterol and have other beneficial actions beyond lipid-lowering
      leading to substantial improvements in cardiovascular morbidity and mortality.
      However, evaluation of the effects of statins to reduce overall morbidity and
      mortality must integrate metabolic consequences of statin therapy with its lipid
      lowering effect. Indeed, reduction in LDL-cholesterol to target level achieved by
      statins does not completely eliminate risk of cardiovascular disease and may
      elevate metabolic risk factors that contribute to dysregulation of metabolic
      homeostasis. This may lead to increased incidence of diabetes and its
      cardiovascular complications that are explained, in part, by reciprocal
      relationships between insulin resistance and endothelial dysfunction. Genetic
      factors may determine 40-60% of total cholesterol levels and 70% of the efficacy
      of statin treatments. Metabolic and cardiovascular phenotypes that are either
      genetically determined or environmentally acquired are also important
      determinants of responses to specific statins. Moreover, differences between
      biological outcomes of specific statins or increasing dosages of statins result
      in differential metabolic actions due to off-target or unknown mechanism that
      have important implications for the use of statins to reduce overall morbidity
      and mortality. In this review, we discuss differential cardiovascular and
      metabolic pleiotropic actions of specific statins that interact in a context
      dependent manner with patient phenotypes and genotypes. These important
      considerations may influence progression of atherosclerosis, risk of diabetes,
      and modulation of insulin resistance that help determine overall morbidity and
      mortality in patients undergoing statin therapy. 

PMID- 23159412
TI  - Comparison of real-time PCR and conventional PCR with two DNA targets for
      detection of Leishmania (Leishmania) infantum infection in human and dog blood
      samples.
AB  - Zoonotic visceral leishmaniasis (VL) is endemic in northwestern Iran. Real-time
      PCR, conventional PCR, and the direct agglutination test (DAT) were used to
      diagnose Leishmania infantum infection in blood samples from 100 domestic dogs
      and 100 humans. Based on clinical evaluation, 82 humans and 72 dogs from the
      endemic area were categorized as having asymptomatic infection, DAT positive with
      no clinical signs of VL, or symptomatic infection, DAT positive with at least one
      sign of VL. Eighteen human samples containing no Leishmania antibodies (DAT(-))
      and 28 dog DAT(-) sera from non-endemic areas with no history of VL constituted
      negative controls. All 46 DAT(-) samples were also negative by Dipstick rK39.
      Bone marrow material was used for parasitological examinations in symptomatic VL,
      and peripheral blood samples were used for detection of L. infantum infection
      using conventional PCR and real-time PCR in non-symptomatic subjects. Two DNA
      targets (ITS1 kDNA) were used for conventional PCR. L. infantum antibodies in
      sera were detected by DAT. Parasitemia was measured by real-time PCR targeting
      kDNA using Taqman Assay. All 72 (100%) symptomatic (38/38) and asymptomatic
      (34/34) dog DAT(+)samples, 45 of 48 (93.8%) symptomatic human DAT(+) samples, and
      32 of 34 (94.1%) human asymptomatic cases were identified by real-time PCR. The
      mean (59.19 vs 12.38 parasite equivalents/mL of blood) and median (16.15 vs 1
      parasite equivalents/mL of blood) ranges of parasitemia were higher in dogs than
      in humans (P<0.05). The highest agreement was obtained between real-time PCR and
      DAT (99% in dogs and 95% in humans). Sensitivity of 100% and 93.9%, specificity
      of 96.4% and 100%, positive predictive values of 98.6% and 100%, and negative
      predictive values of 100% and 78.3% were found by real-time PCR for dog and human
      samples, respectively.

PMID- 23159413
TI  - Comparative analysis of different methods to enhance porcine circovirus 2
      replication.
AB  - Porcine circovirus 2 (PCV2) is an extremely slow-growing virus, and PCV2
      infection and replication in cell culture yield very low viral titers. The
      effects of different methods of PCV2 cultivation in vitro were compared with the
      purpose of increasing viral yield. The results showed that treatment with IL-2,
      ConA, and D-glucosamine increased PCV2 yield more effectively than other
      treatments. Additionally, treatment with IL-2, ConA, D-glucosamine and MbetaCD
      consistently increased PCV2 infection in PK-15 cells during consecutive viral
      passages. A combinatorial treatment with ConA, MbetaCD and D-glucosamine
      increased PCV2 yield significantly in PK-15 cells, to 1.81*10(10) genome copy
      numbers per mL of cell lysate at 72 hpi, and the viral titer (-lgTCID50/100 MUL)
      was 8.6. The results of this study may be helpful for the investigation of PCV2
      replication and the production of a PCV2 vaccine.

PMID- 23159415
TI  - Import of phosphatidylserine to and export of phosphatidylethanolamine molecular
      species from mitochondria.
AB  - Heavy isotope-labeled ethanolamine and serine as well as exogenous PE and PS
      species were used to study trafficking of phosphatidylethanolamine (PE) and 
      serine (PS) molecular species between the endoplasmic reticulum (ER) and
      mitochondria in HeLa cells. Import of both endogenous and exogenous PS to IMM was
      a relatively slow process (T1/2=several hours), but depended on the acyl chains.
      In particular, the 38:4 and 38:5 species were imported more efficiently compared
      to the other PS species. Knock-down of Mitofusin 2 or Mitostatin had no
      detectable effect on PS import to mitochondria, suggesting that the ER
      mitochondria contacts regulated by these proteins are not essential. Knock-down
      of PS synthase 1 inhibited PS decarboxylation, suggesting that import of PS to
      mitochondria is coupled to its synthesis. Also the export of PE from IMM to
      microsomes is a relatively slow process, but again depends markedly on the acyl
      chain structure. Most notably, the polyunsaturated 38:4 and 38:5 PE species were
      less efficiently exported, which together with rapid import of the PS precursors
      most probably explains their enrichment in IMM. PE synthesized via the CDP
      ethanolamine was also imported to IMM, but most of the PE in this membrane
      derives from imported PS. In contrast to PS, all PC species made in Golgi/ER
      translocated similarly and rapidly to IMM. In conclusion, selective translocation
      of PS species and PS-derived PE species between ER and mitochondria plays a major
      role in phospholipid homeostasis of these organelles.

PMID- 23159414
TI  - The glycolipid transfer protein (GLTP) domain of phosphoinositol 4-phosphate
      adaptor protein-2 (FAPP2): structure drives preference for simple neutral
      glycosphingolipids.
AB  - Phosphoinositol 4-phosphate adaptor protein-2 (FAPP2) plays a key role in
      glycosphingolipid (GSL) production using its C-terminal domain to transport newly
      synthesized glucosylceramide away from the cytosol-facing glucosylceramide
      synthase in the cis-Golgi for further anabolic processing. Structural homology
      modeling against human glycolipid transfer protein (GLTP) predicts a GLTP-fold
      for FAPP2 C-terminal domain, but no experimental support exists to warrant
      inclusion in the GLTP superfamily. Here, the biophysical properties and
      glycolipid transfer specificity of FAPP2-C-terminal domain have been
      characterized and compared with other established GLTP-folds. Experimental
      evidence for a GLTP-fold includes: i) far-UV circular dichroism (CD) showing
      secondary structure with high alpha-helix content and a low thermally-induced
      unfolding transition (~41 degrees C); ii) near-UV-CD indicating only subtle
      tertiary conformational change before/after interaction with membranes
      containing/lacking glycolipid; iii) Red-shifted tryptophan (Trp) emission
      wavelength maximum (lambda(max)~352nm) for apo-FAPP2-C-terminal domain consistent
      with surface exposed intrinsic Trp residues; iv) 'signature' GLTP-fold Trp
      fluorescence response, i.e., intensity decrease (~30%) accompanied by strongly
      blue-shifted lambda(max) (~14nm) upon interaction with membranes containing
      glycolipid, supporting direct involvement of Trp in glycolipid binding and
      enabling estimation of partitioning affinities. A structurally-based preference
      for other simple uncharged GSLs, in addition to glucosylceramide, makes human
      FAPP2-GLTP more similar to fungal HET-C2 than to plant AtGLTP1 (glucosylceramide
      specific) or to broadly GSL-selective human GLTP. These findings along with the
      distinct mRNA exon/intron organizations originating from single-copy genes on
      separate human chromosomes suggest adaptive evolutionary divergence by these two
      GLTP-folds.

PMID- 23159416
TI  - Activation of glibenclamide-sensitive ATP-sensitive K+ channels during beta
      adrenergically induced metabolic stress produces a substrate for atrial
      tachyarrhythmia.
AB  - BACKGROUND: Cardiac ATP-sensitive K(+) channels have been suggested to contribute
      to the adaptive physiological response to metabolic challenge after beta
      adrenoceptor stimulation. However, an increased atrial K(+)-conductance might be
      expected to be proarrhythmic. We investigated the effect of ATP-sensitive K(+)
      channel blockade on the electrophysiological responses to beta-adrenoceptor
      induced metabolic challenge in intact atria. METHODS AND RESULTS: Atrial
      electrograms were recorded from the left atrial epicardial surface of Langendorff
      perfused rat hearts using a 5*5 electrode array. Atrial effective refractory
      period and conduction velocity were measured using an S(1)-S(2) protocol. The
      proportion of hearts in which atrial tachyarrhythmia was produced by burst-pacing
      was used as an index of atrial tachyarrhythmia-inducibility. Atrial nucleotide
      concentrations were measured by high performance liquid chromatography. Perfusion
      with >=10(-9) mol/L of the beta-adrenoceptor agonist, isoproterenol (ISO),
      resulted in a concentration-dependent reduction of atrial effective refractory
      period and conduction velocity. The ISO-induced changes produced a proarrhythmic
      substrate such that atrial tachyarrhythmia could be induced by burst-pacing.
      Atrial [ATP] was significantly reduced by ISO (10(-6) mol/L). Perfusion with
      either of the ATP-sensitive K(+) channel blockers, glibenclamide (10(-5) mol/L)
      or tolbutamide (10(-3) mol/L), in the absence of ISO had no effect on basal
      atrial electrophysiology. On the other hand, the proarrhythmic substrate induced
      by 10(-6) mol/L ISO was abolished by either of the sulfonylureas, which prevented
      induction of atrial tachyarrhythmia. CONCLUSIONS: Atrial ATP-sensitive K(+)
      channels activate in response to beta-adrenergic metabolic stress in Langendorff
      perfused rat hearts, resulting in a proarrhythmic substrate.

PMID- 23159417
TI  - Atrioventricular node reentrant tachycardia in patients with congenitally
      corrected transposition of the great arteries and results of radiofrequency
      catheter ablation.
AB  - BACKGROUND: We sought to investigate the feasibility of radiofrequency catheter
      ablation of atrioventricular node reentrant tachycardia and the ideal site for
      slow pathway (SP) ablation in congenitally corrected transposition of the great
      arteries. METHODS AND RESULTS: Nine patients with congenitally corrected
      transposition of the great arteries referred for catheter ablation of
      atrioventricular node reentrant tachycardia were studied. A single His potential
      was recorded in 8 patients (89%, 6 {S,L,L} and 2 {I,D,D}). The earliest atrial
      activation during retrograde atrioventricular node conduction occurred at His
      bundle region (HBE; n=7) or shifting from HBE to coronary sinus ostium (n=1,
      {S,L,L}). Two anatomically separate His potentials were recorded in 1 patient
      (11%, {S,L,L}), one at the anteroseptum (HBE-1) and the other at the confluence
      of the pulmonary and mitral annulus (HBE-2). In 8 cases with a single His
      potential recorded, SP was abated at the posterior-midseptum, 2 ({S,L,L}) at the
      right posteroseptum, 1 ({S,L,L}) at the left posteroseptum, and 5 (3 {S,L,L} and
      2 {I,D,D}) at the midseptum after failure of energy application at the
      posteroseptum. Junctional rhythm was observed during radiofrequency catheter
      ablation in all 8 of the cases. In the remaining patient with 2 anatomically
      separate His potentials recorded, SP was successfully ablated from the confluence
      of the pulmonary and mitral annulus, slightly below the HBE-2. Junctional rhythm
      was also induced during radiofrequency catheter ablation. CONCLUSIONS: In {S,L,L}
      or {I,D,D}, radiofrequency catheter ablation of atrioventricular node reentrant
      tachycardia is feasible. SP input region can mainly be found in the posterior
      midseptum, especially in patients with single penetrating atrioventricular nodes.
      SP could usually be successfully ablated in these regions.

PMID- 23159418
TI  - The function of efference copy signals: implications for symptoms of
      schizophrenia.
AB  - Efference copy signals are used to reduce cognitive load by decreasing sensory
      processing of reafferent information (those incoming sensory signals that are
      produced by an organism's own motor output). Attenuated sensory processing of
      self-generated afferents is seen across species and in multiple sensory systems
      involving many different neural structures and circuits including both cortical
      and subcortical structures with thalamic nuclei playing a particularly important
      role. It has been proposed that the failure to disambiguate self-induced from
      externally generated sensory input may cause some of the positive symptoms in
      schizophrenia such as auditory hallucinations and delusions of passivity. Here,
      we review the current data on the role of efference copy signals within different
      sensory modalities as well as the behavioral, structural and functional
      abnormalities in clinical groups that support this hypothesis.

PMID- 23159419
TI  - The Optimal Viewing Position effect in the lower visual field.
AB  - The Optimal Viewing Position (OVP) effect shows that word identification is best
      when the eyes first fixate near the centre of words. While this effect has been
      extensively studied in normal reading conditions, it has not been much
      investigated for words in the periphery. Here, we compared, in a perceptual
      identification task, the OVP effect for words presented either on the line of
      sight or in the lower visual field. Results confirmed the existence of an OVP
      effect for both central and vertically-shifted words but this effect was
      significantly weaker in the lower visual field. This finding provides further
      evidence for an important role of letter visibility in determining the shape of
      the OVP phenomenon. It also indicates that aligning the eyes with the centre of
      words is not as critical for vertically-shifted words. Implications for patients
      with central field loss who are forced to read in the periphery are discussed.

PMID- 23159420
TI  - Sella turcica morphology and the pituitary gland-a new contribution to
      craniofacial diagnostics based on histology and neuroradiology.
AB  - The present review summarizes two decades of published and unpublished studies on
      normal and pathological development of sella turcica and pituitary gland in
      humans. The pathological conditions are studied in known genotype deviations,
      syndromes, and other malformations. The studies include histological analyses of
      human prenatal material and profile radiographic analyses of human postnatal
      material, supplemented in a few cases with neuroradiology. Prenatal and postnatal
      results are compared. Similarities between prenatal and postnatal deviations in
      sella turcica morphology were demonstrated. Malformations in the pituitary gland
      were observed in several cases. For diagnostic purposes, the review distinguishes
      between deviations in the anterior wall and in the posterior wall of the sella
      turcica. Deviations in the anterior wall seem to be associated with deviations
      specifically in the frontonasal developmental field, while deviations in the
      posterior wall are often connected with malformations in the posterior
      structures, e.g. the cerebellum. In normal cases, minor variations in morphology
      are observed. In each pathological case, a specific malformation pattern was
      observed in sella turcica morphology, varying from mild to severe phenotype. The
      malformation in the sella turcica/pituitary gland can be associated with a
      malformation within a developmental field that forms the craniofacial region
      (frontonasal, maxillary, palatal, and mandibular fields), sometimes also
      involving the brain stem, thymus, thyroid, and heart (velocardiofacial syndrome).
      Pathological sella turcica morphology can also be associated with malformations
      in the cerebellum and larynx (Cri-du-Chat syndrome). This review demonstrates the
      value of combining profile radiographic diagnostics with neuroradiological
      diagnostics in cases with malformed sella turcicae. 

PMID- 23159421
TI  - Predicting compliance for mandible advancement splint therapy in 96 obstructive
      sleep apnea patients.
AB  - The treatment of choice in obstructive sleep apnea (OSA) is continuous positive
      airway pressure (CPAP). Mandible advancement splint (MAS) offers an option for
      patients with mild or moderate OSA, who refuse or are unable to tolerate CPAP.
      The aim of the study was to find predictive factors in OSA for MAS therapy. The
      study group comprised 96 consecutive OSA patients who were sent for MAS therapy
      during 2008. Data were collected on the patients' general and dental condition,
      diagnosis, and treatment for OSA. Panoramic and cephalometric radiographs were
      analysed. The treatment compliance rate and problems with the use of the MAS were
      recorded. This rate was 57% and the significant affecting factors were protrusion
      of the mandible with MAS during the adaptation to the appliance as well as
      shorter maxillary and mandible lengths. The compliance of the MAS therapy was
      best in patients with short maxilla and mandible, which should be taken into
      consideration when planning MAS therapy for OSA patients. Finally, a sleep study
      should be part of the follow-up in this patient population.

PMID- 23159422
TI  - Radiation risk-benefit in orthodontics.

PMID- 23159423
TI  - Chronic subdural hematoma after neurosurgical procedures.

PMID- 23159424
TI  - Neuroprotective effects of progesterone in spinal cord ischemia in rabbits.
AB  - BACKGROUND: This experimental study was performed to investigate the
      neuroprotective effects of progesterone on spinal cord ischemia in rabbits.
      METHODS: Eighteen female New Zealand white rabbits were used in this study.
      Rabbits were randomized into 3 groups. Spinal cord ischemia was induced by
      clamping the abdominal aorta from a point just inferior to the left renal artery
      to the aortic bifurcation for a period of 30 minutes. Group 1 served as the
      control group, and groups 2 and 3 received intraperitoneal progesterone
      immediately after the onset of reperfusion, at a dose of 8 mg/kg. Two hours after
      reperfusion, the animals in group 1 were killed. Four hours after reperfusion,
      the animals in group 2 were killed, and 6 hours after reperfusion, the group 3
      rabbits were killed. Spinal cords were removed and fixed in 10% formalin in a
      phosphate buffer. Neuronal injury was evaluated by a pathologist who was blinded
      to the treatment groups, and 5 sections per animal were evaluated. The number of
      intact large motor neuron cells in the ventral grey matter region was counted.
      RESULTS: The analysis revealed that the average mean arterial pressure for group
      1 was significantly higher than that for group 2, and the mean sacrificed
      pressure value for group 1 was significantly higher than that for group 3 (P <
      .05). The number of intact neurons in group 1 was significantly lower than the
      number of intact neurons found in both groups 2 and 3 (P < .05). No other
      statistically significant differences were found between the groups. CONCLUSION:
      The findings from the present study indicate that progesterone effectively
      protects the spinal cord tissues against ischemic damage in the setting of
      decreased perfusion.

PMID- 23159425
TI  - Emerging applications of low-dose ketamine for pain management in the ED.

PMID- 23159426
TI  - High-flow oxygen, a therapeutic bridge while awaiting thrombolysis in pulmonary
      embolism?

PMID- 23159427
TI  - Impact of stylet use in a simulated difficult airway model.
AB  - BACKGROUND: Stylet use during endotracheal intubation (ETI) is variable across
      medical specialty and geographic location; however, few objective data exist
      regarding the impact of stylet use on ETI performance. OBJECTIVE: We evaluated
      the impact of stylet use on the time required to perform ETI in cases of
      simulated difficult airways in novice and experienced providers. METHODS: We
      performed a prospective, randomized observational study of experienced (attending
      anesthesiologists and emergency physicians) vs inexperienced airway providers
      (emergency medical technician, paramedic and medical students) comparing the use
      of stylet vs no stylet in random order using a simulated difficult airway. The
      primary outcome was attempt time for each of 6 attempts defined as entry of the
      laryngoscope in the mouth until successfully passing the endotracheal tube past
      the vocal cords. We analyzed the data using descriptive statistics including
      means with SDs and t tests. We used generalized estimating equations to evaluate
      potential changes in the attempt time over multiple attempts. RESULTS: There were
      23 providers per group. The mean (SD) inexperienced attempt time in seconds was
      25.88 (28.46) and 10.50 (5.47) for experienced providers (P < .0001). Stylet use
      did not alter attempt time for either group. When adjusting for stylet use, the
      attempt time did not change over repeated intubations (P = .541). When adjusting
      for experience status, inexperienced intubators had shorter attempt times with
      each successive trial, whereas experienced intubators attempt times remained
      constant (P < .001). CONCLUSION: Stylet use does not improve attempt time in a
      simulated difficult airway model for either inexperienced or experienced
      intubators.

PMID- 23159428
TI  - Cardiopulmonary resuscitation: is the ED visit an opportunity to recommend
      education?

PMID- 23159429
TI  - Electrolyte abnormalities and laboratory findings in patients with out-of
      hospital cardiac arrest who have kidney disease.
AB  - PURPOSES: Although electrolyte abnormalities have been generally considered the
      major cause of out-of-hospital cardiac arrest (OHCA) in patients with kidney
      disease (KD), this association has never been prospectively validated. METHODS: A
      prospective, observational study was conducted in a tertiary university hospital
      between January 2008 and December 2009. The study sample consisted of
      consecutively admitted patients with nontraumatic OHCA. Based on the estimated
      glomerular filtration rate (eGFR, unit: milliliters per minute per 1.73 m(2)),
      the enrollees were divided into 3 groups: group A (normal kidney function or mild
      KD; eGFR, 60.0), group B (moderate KD; eGFR between 15.0 and 59.9), and group C
      (severe KD; eGFR<15.0 or on dialysis). The laboratory findings of the groups were
      compared. Two-tailed P values less than .005 were considered significant.
      RESULTS: Two hundred thirty-four enrollees (137 were male) were divided into 3
      groups: group A (n = 51; 21.8%), group B (n = 128; 54.7%), and group C (n = 55;
      23.5%). Compared with the other 2 groups, group C presented significantly higher
      serum potassium and magnesium and lower pH and hemoglobin level (all P < .005).
      After stratifications of the significant variables, a post hoc analysis revealed
      that group C presented significantly higher incidences of hypermagnesemia (Mg
      >2.5 mmol/L) and severe hyperkalemia (K >6.5 mmol/L) (both P < .005) than the
      other 2 groups. The odds ratios of the incidence of severe hyperkalemia in group
      C was 3.37 (95% confidence intervals, 1.46-7.77) compared with group A (50.9% vs
      23.5%, P < .005). CONCLUSIONS: Severe hyperkalemia is common in patients with
      OHCA who have severe KD and should be considered during resuscitation for these
      patients.

PMID- 23159430
TI  - The critical care literature 2011.

PMID- 23159431
TI  - Pocket mobile smartphone system for the point-of-care submandibular
      ultrasonography.
AB  - BACKGROUND: Focused ultrasonography of the airway may be useful in the prediction
      of difficult intubation. The wider use of sonography in quantitative airway
      assessment may depend on the availability of highly portable, inexpensive, and
      accurate ultrasound systems. Pocket-sized ultrasound devices are emerging as a
      useful tool for point-of-care ultrasonography. The aim of this study was to
      evaluate the suprahyoid airway of healthy volunteers using a smartphone-based
      ultrasound imaging system in comparison with a platform-based machine. METHODS:
      Mobisante MobiUS SP1 system with 2 mechanical sector (3.5 and 7.5 MHz) probes was
      used to acquire images of the tongue and measure the diameter of the hyomental
      muscle in the mouth floor. In the same group of subjects, imaging and
      measurements were repeated using BK Medical Flex Focus 400 ultrasound system with
      linear (18 MHz ) and curved 5 (MHz) transducers. The MobiUS system was also used
      to image plastic cylinders and procedure needles embedded in tofu bars. Outside
      diameters of cylinders were measured using digital calipers and sonography.
      RESULTS: The mean diameter of the hyomental muscle in 10 healthy volunteers was
      7.22 +/- 1.6 mm using BK 18 MHz probe, 7.11 +/- 1.7 mm using MobiUS 7.5 MHz
      probe, and 7.84 +/- 2 mm using MobiUS 3.5 MHz probe. These means were not
      statistically different (BK vs Mo 7.5, P = .74, and BK vs Mo 3.5, P = .13). The
      mean outside diameter of plastic cylinders measured with digital calipers was
      10.1 +/- 0.2 mm (n = 5) vs 9.8 +/- 0.3 mm and 10.2 +/- 0.2 mm using 3.5 and 7.5
      MHz probes, respectively. These means were not statistically different (calipers
      vs Mo 3.5, P = .16 and calipers vs Mo 7.5, P = .39). CONCLUSION: Mobisante MobiUS
      system was able to acquire clinically useful images of the suprahyoid airway and
      muscular architecture in the mouth floor and allowed accurate measurements of
      linear distances.

PMID- 23159432
TI  - Association between ED crowding and delay in resuscitation effort.
AB  - STUDY OBJECTIVE: Few investigations have been performed that address why
      emergency department (ED) crowding is associated with an increase in hospital
      mortality for emergency patients. The purpose of this study was to evaluate
      whether ED crowding is associated with delayed resuscitation efforts (DREs) that
      resulted in hospital mortality. METHODS: This is a retrospective observational
      study performed at a single urban tertiary ED. All adult patients who entered the
      resuscitation room and underwent resuscitative procedures from October 2008 to
      May 2010 were enrolled in the study. Demographic data were collected from a
      designed resuscitation room registry. The ED electronic log data were used for
      calculating the crowding status. A crowded day was defined as a daily number of
      patients greater than 93, which was a cut-off derived from a sensitivity
      analysis. The primary outcome was a DRE, which occurred when a patient was
      located in the hallway or waiting room, then entered the resuscitation room, and
      received resuscitative procedures after the patient had clinically deteriorated.
      A secondary outcome was hospital mortality. Matched samples were selected using
      propensity scores to consider the clinical parameters and emergency severity
      index when the patients received triage immediately after registration. A
      logistic regression analysis was modeled to estimate the odds ratios (ORs) with
      95% confidence intervals (CIs) on the DRE. RESULTS: A total of 1296 patients
      underwent resuscitative procedures in the resuscitation room. Of these, 226
      (17.4%) were classified as the DRE group. A final 396 cases (30.6%) were matched
      and analyzed between DRE and non-DRE using the propensity score. The incidence of
      DRE was significantly higher on crowded days (OR, 2.00; 95% CI, 1.28-3.15).
      Mortality during the ED stay or during the total hospital stay was significantly
      higher in the DRE group (OR, 3.39; 95% CI, 1.22-9.45 and OR, 3.96; 95% CI, 2.28
      6.88, respectively) compared with the non-DRE group. CONCLUSION: Delays in
      resuscitation efforts occurred more frequently on crowded days and were
      associated with higher in-hospital mortality.

PMID- 23159433
TI  - Postpartum spontaneous intracranial hypotension.

PMID- 23159434
TI  - The effect of overexpression of PGC-1alpha on the mtDNA4834 common deletion in a
      rat cochlear marginal cell senescence model.
AB  - Aging is a natural process usually defined as a progressive loss of function with
      an accumulation of senescent cells. The clinical manifestations of this process
      include age-related hearing loss (AHL)/presbycusis. Several investigations
      indicated the association between a mitochondrial common deletion (CD) (mtDNA
      4977-bp deletion in humans, corresponding to 4834-bp deletion in rats) and
      presbycusis. Previous researches have shown that peroxisome proliferator
      activated receptor-gamma coactivator-1alpha (PGC-1alpha) is a key regulator of
      mitochondrial biogenesis and energy metabolism. However, the expression of PGC
      1alpha in the inner ear and the possible effect of PGC-1alpha on presbycusis are
      not clear. Our data demonstrated the distribution of PGC-1alpha and its
      downstream transcription factors nuclear respiratory factor-1 (NRF-1),
      mitochondrial transcription factor A (Tfam) and nuclear factor kappaB (NF-kappaB)
      in marginal cells (MCs) for the first time. To explore the role of PGC-1alpha in
      cellular senescence, we established a model of marginal cell senescence harboring
      the mtDNA4834 common deletion induced by d-galactose. We also found that PGC
      1alpha and its downstream transcription factors compensatorily increased in our
      cell senescence model. Furthermore, the overexpression of PGC-1alpha induced by
      transfection largely increased the expression levels of NRF-1 and TFAM and
      significantly decreased the expression level of NF-kappaB in the cell senescence
      model. And the levels of CD, senescent cells and apoptotic cells in the cell
      model decreased after PGC-1alpha overexpression. These results suggested that PGC
      1alpha might protect MCs in this cell model from senescence through a nuclear
      mitochondrial interaction and against apoptosis. Our study may shed light on the
      pathogenesis of presbycusis and provide a new therapeutic target for presbycusis.

PMID- 23159435
TI  - Monocyte-suppressing effects of simvastatin in patients with isolated
      hypertriglyceridemia.
AB  - BACKGROUND: No previous study investigated statin action on monocyte cytokine
      release and systemic inflammation in patients with isolated hypertriglyceridemia.
      METHODS: Our study included 43 subjects with isolated hypertriglyceridemia and
      peripheral artery stenosis randomly allocated to one of two groups, treated for
      12 weeks with either simvastatin (40 mg twice daily) or placebo. Plasma lipids,
      glucose homeostasis markers, plasma C-reactive protein and monocyte cytokine
      release were determined on the day of allocation and at the end of the treatment
      period. RESULTS: Simvastatin, but not placebo, reduced monocyte release of tumor
      necrosis factor-alpha, interleukin-6, interleukin-1beta and monocyte
      chemoattractant protein-1, as well decreased plasma levels of C-reactive protein.
      CONCLUSIONS: Our study shows that simvastatin reduces monocyte secretory function
      and has systemic anti-inflammatory properties in patients with isolated
      hypertriglyceridemia.

PMID- 23159436
TI  - Haploinsufficiency of the paternal-effect gene Dnmt3L results in transient DNA
      hypomethylation in progenitor cells of the male germline.
AB  - STUDY QUESTION: How does haploinsufficiency of the paternal-effect gene Dnmt3L
      affect DNA methylation establishment and stability in the male germline? SUMMARY
      ANSWER: Reduced expression of DNMT3L in male germ cells, associated with
      haploinsufficiency of the paternal-effect gene Dnmt3L, results in abnormal
      hypomethylation of prenatal germline progenitor cells. WHAT IS KNOWN ALREADY: The
      DNA methyltransferase regulator Dnmt3-Like (Dnmt3L) is a paternal-effect gene
      required for DNA methylation acquisition in male germline stem cells and their
      precursors. In males, DNMT3L deficiency causes meiotic abnormalities and
      infertility. While Dnmt3L heterozygous males are fertile, they have abnormalities
      in X chromosome compaction and postmeiotic gene expression and sire offspring
      with sex chromosome aneuploidy. It has been proposed that the paternal effects of
      Dnmt3L haploinsufficiency are due to epigenetic defects in early male germ cells.
      DNA methylation is an essential epigenetic modification essential for normal germ
      cell development. Since patterns of DNA methylation across the genome are
      initially acquired in prenatal male germ cells, perturbations in methylation
      could contribute to the epigenetic basis of the paternal effects in Dnmt3L(+/-)
      males. STUDY DESIGN, SIZE, DURATION: This is a cross-sectional study of DNA
      methylation in Dnmt3L(+/+) versus Dnmt3L(+/-) male germ cells collected from mice
      at 16.5 days post-coitum (dpc), Day 6 and Day 70 (n = 3 per genotype, each n
      represents a pool of 2-20 animals). Additionally, DNA methylation was compared in
      enriched populations of spermatogonial stem cells (SSC)/progenitor cells from
      Dnmt3L(+/+) and Dnmt3L(+/-) males following ~ 2 months in culture. MATERIALS,
      SETTING, METHODS: DNA methylation at intergenic loci along chromosomes 9 and X
      was examined by quantitative analysis of DNA methylation by real-time polymerase
      chain reaction at the time of initial acquisition of epigenetic patterns in the
      prenatal male germline (16.5 dpc) and compared with patterns in early post-natal
      spermatogonia (Day 6) and in spermatozoa in mice. DNA methylation status at CpG
      rich sites across the genome was assessed in spermatogonial precursors from Day 4
      male mice using restriction landmark genomic scanning. MAIN RESULTS AND THE ROLE
      OF CHANCE: At 16.5 dpc, 42% of intergenic loci examined along chromosome 9 and
      10% of those along chromosome X were hypomethylated in Dnmt3L heterozygotes. By
      Day 6 and in spermatozoa, germ cell DNA methylation was similar in heterozygous
      and wild-type mice. DNA methylation stability of acquired patterns in wild-type
      and Dnmt3L(+/-) SSC/progenitor cell culture was analyzed at numerous loci across
      the genome in cells cultured in vitro and collected at passages 6-28. While the
      methylation of most loci was stable in culture over time, differences at ~ 1% of
      sites were found between Dnmt3L(+/-) and Dnmt3L(+/+) cultures. LIMITATIONS,
      REASONS FOR CAUTION: Evaluation of DNA methylation in SSCs can only be performed
      after a period of culture limiting the investigation to changes observed during
      culture when compared with DNA methylation differences between genotypes that
      could be present at the beginning of culture establishment. WIDER IMPLICATIONS OF
      THE FINDINGS: The DNA methylation defects described here in prenatal male
      germline progenitor cells and SSC culture are the earliest epigenetic
      perturbations yet identified for a mammalian paternal-effect gene and may
      influence downstream epigenetic events in germ cells at later stages of
      development. Together, the results provide evidence of a 'window' of
      susceptibility in prenatal male germ cell precursors for the induction of
      epimutations due to genetic perturbations and, potentially, in utero
      environmental exposures.

PMID- 23159437
TI  - The DNA damage- and transcription-associated protein paxip1 controls thymocyte
      development and emigration.
AB  - Histone 3 lysine 4 trimethylation (H3K4me3) is associated with promoters of
      active genes and found at hot spots for DNA recombination. Here we have shown
      that PAXIP1 (also known as PTIP), a protein associated with MLL3 and MLL4
      methyltransferase and the DNA damage response, regulates RAG-mediated cleavage
      and repair during V(D)J recombination in CD4(+) CD8(+) DP thymocytes. Loss of
      PAXIP1 in developing thymocytes diminished Jalpha H3K4me3 and germline
      transcription, suppressed double strand break formation at 3' Jalpha segments,
      but resulted in accumulation of unresolved T cell receptor alpha-chain gene
      (Tcra) breaks. Moreover, PAXIP1 was essential for release of mature single
      positive (SP) alphabeta T cells from the thymus through transcriptional
      activation of sphingosine-1-phosphate receptor S1pr1 as well as for natural
      killer T cell development. Thus, in addition to maintaining genome integrity
      during Tcra rearrangements, PAXIP1 controls distinct transcriptional programs
      during DP differentiation necessary for Tcra locus accessibility, licensing
      mature thymocytes for trafficking and natural killer T cell development.

PMID- 23159438
TI  - Network analysis reveals centrally connected genes and pathways involved in CD8+
      T cell exhaustion versus memory.
AB  - Exhausted CD8(+) T cells function poorly and are negatively regulated by
      inhibitory receptors. Transcriptional profiling has identified gene expression
      changes associated with exhaustion. However, the transcriptional pathways
      critical to the differences between exhausted and functional memory CD8(+) T
      cells are unclear. We thus defined transcriptional coexpression networks to
      define pathways centrally involved in exhaustion versus memory. These studies
      revealed differences between exhausted and memory CD8(+) T cells including the
      following: lack of coordinated transcriptional modules of quiescence during
      exhaustion, centrally connected hub genes, pathways such as transcription
      factors, genes involved in regulation of immune responses, and DNA repair genes,
      as well as differential connectivity for genes including T-bet, Eomes, and other
      transcription factors. These data identify pathways involved in CD8(+) T cell
      exhaustion, and highlight the context-dependent nature of transcription factors
      in exhaustion versus memory.

PMID- 23159439
TI  - The CD27 and CD70 costimulatory pathway inhibits effector function of T helper 17
      cells and attenuates associated autoimmunity.
AB  - T helper 17 (Th17) cells protect against infection but also promote inflammation
      and autoimmunity. Therefore, the factors that govern Th17 cell differentiation
      are of special interest. The CD27 and CD70 costimulatory pathway impeded Th17
      effector cell differentiation and associated autoimmunity in a mouse model of
      multiple sclerosis. CD27 or CD70 deficiency exacerbated disease, whereas
      constitutive CD27 signaling strongly reduced disease incidence and severity. CD27
      signaling did not impact master regulators of T helper cell lineage commitment
      but selectively repressed transcription of the key effector molecules interleukin
      17 (IL-17) and the chemokine receptor CCR6 in differentiating Th17 cells. CD27
      mediated this repression at least in part via the c-Jun N-terminal kinase (JNK)
      pathway that restrained IL-17 and CCR6 expression in differentiating Th17 cells.
      CD27 signaling also resulted in epigenetic silencing of the Il17a gene. Thus,
      CD27 costimulation via JNK signaling, transcriptional, and epigenetic effects
      suppresses Th17 effector cell function and associated pathological consequences.

PMID- 23159440
TI  - Reactive oxygen species-induced actin glutathionylation controls actin dynamics
      in neutrophils.
AB  - The regulation of actin dynamics is pivotal for cellular processes such as cell
      adhesion, migration, and phagocytosis and thus is crucial for neutrophils to
      fulfill their roles in innate immunity. Many factors have been implicated in
      signal-induced actin polymerization, but the essential nature of the potential
      negative modulators are still poorly understood. Here we report that NADPH
      oxidase-dependent physiologically generated reactive oxygen species (ROS)
      negatively regulate actin polymerization in stimulated neutrophils via driving
      reversible actin glutathionylation. Disruption of glutaredoxin 1 (Grx1), an
      enzyme that catalyzes actin deglutathionylation, increased actin
      glutathionylation, attenuated actin polymerization, and consequently impaired
      neutrophil polarization, chemotaxis, adhesion, and phagocytosis. Consistently,
      Grx1-deficient murine neutrophils showed impaired in vivo recruitment to sites of
      inflammation and reduced bactericidal capability. Together, these results present
      a physiological role for glutaredoxin and ROS- induced reversible actin
      glutathionylation in regulation of actin dynamics in neutrophils.

PMID- 23159441
TI  - Super-resolution imaging of EC coupling protein distribution in the heart.
AB  - The cardiac ryanodine receptor (RyR) plays a central role in the control of
      contractile function of the heart. In cardiac ventricular myocytes RyRs and
      associated Ca(2+) handling proteins, including membrane Ca(2+) channels, Ca(2+)
      pumps and other sarcolemmal and sarcoplasmic reticulum proteins interact to set
      the time course and amplitude of the electrically triggered cytosolic Ca(2+)
      transient. It has become increasingly clear that protein distribution and
      clustering on the nanometer scale is critical in determining the interaction of
      these proteins and the resulting properties of cardiac Ca(2+) handling. Such
      intricate near-molecular scale detail cannot be visualized with conventional
      fluorescence microscopy techniques (e.g. confocal microscopy) but it has recently
      become accessible with optical super-resolution techniques. These techniques
      retain the advantages of fluorescent marker technology, i.e. high specificity and
      excellent contrast, but have a spatial resolution approaching 10nm, i.e. objects
      not much further apart than 10nm can be distinguished, previously only attainable
      with electron microscopy. We review the use of these novel imaging techniques for
      the study of protein distribution in cardiac ventricular myocytes and discuss
      technical considerations as well as recent findings using super-resolution
      imaging. An emphasis is on single molecule localization based super-resolution
      approaches and their use to reveal the complexity of RyR cluster morphology,
      placement and relationship to other excitation-contraction coupling proteins.
      Super-resolution imaging approaches have already demonstrated their utility for
      the study of cardiac structure-function relationships and we anticipate that
      their use will rapidly increase and help improve our understanding of cardiac
      Ca(2+) regulation.

PMID- 23159442
TI  - The Ca-calmodulin dependent kinase II: a promising target for future
      antiarrhythmic therapies?
AB  - Treating arrhythmias is a challenge for clinicians because pharmacological
      therapies are often ineffective or have severe side effects. Patients with heart
      failure frequently present with supreventricular and ventricular arrhythmias. New
      antiarrhythmic therapies are needed that modulate the specific pathomechanisms
      underlying the development of cardiac arrhythmias and may have a better safety
      profile. The Ca-calmodulin dependent kinase II (CaMKII) seems to be involved in
      the development of heart failure and arrhythmias and may therefore be a promising
      target for the development of antiarrhythmic therapies. The current review aims
      at discussing some novel as well as known cytosolic and sarcolemmal mechanisms
      involved in CaMKII-dependent arrhythmias without being able to cover all aspects
      known in the field.

PMID- 23159443
TI  - Impact of hand orientation on bimanual finger coordination in an eight-finger
      tapping task.
AB  - In the present experiment we examined whether a symmetry tendency in bimanual
      finger coordination is observable in an experimental setting resembling a serial
      learning task and whether this tendency is defined in hand-based coordinates.
      Participants performed an eight-finger bimanual coordination task, in which they
      responded to sequences of visual stimuli by sequences of tapping movements.
      Visual stimuli triggered flexion of fingers, which were parallel or mirror
      symmetrical in respect to the body midline. Additionally, the orientation of the
      right hand relative to the left hand was varied. When both hands had the same
      orientation, the mirror symmetrical mode was more stable than the parallel mode.
      When both hands had different orientations, in contrast, the parallel mode was
      more stable. This result suggests that the tendency towards mirror symmetry was
      defined in hand-based coordinates. This outcome is relevant for the research of
      skill learning regarding the issue of whether acquired sequence knowledge is tied
      to specific effectors.

PMID- 23159444
TI  - Modulation of human motoneuron activity by a mental arithmetic task.
AB  - This study aimed to determine whether the performance of a mental task affects
      motoneuron activity. To this end, the tonic discharge pattern of wrist extensor
      motor units was analyzed in healthy subjects while they were required to maintain
      a steady wrist extension force and to concurrently perform a mental arithmetic
      (MA) task. A shortening of the mean inter-spike interval (ISI) and a decrease in
      ISI variability occurred when MA task was superimposed to the motor task. Aloud
      and silent MA affected equally the rate and variability of motoneuron discharge.
      Increases in surface EMG activity and force level were consistent with the
      modulation of the motor unit discharge rate. Trial-by-trial analysis of the
      characteristics of motor unit firing revealed that performing MA increases
      activation of wrist extensor SMU. It is suggested that increase in muscle spindle
      afferent activity, resulting from fusimotor drive activation by MA, may have
      contributed to the increase in synaptic inputs to motoneurons during the mental
      task performance, likely together with enhancement in the descending drive. The
      finding that a mental task affects motoneuron activity could have consequences in
      assessment of motor disabilities and in rehabilitation in motor pathologies.

PMID- 23159445
TI  - Diagnostic opportunities based on skin biomarkers.
AB  - Systemic as well as localized skin diseases modify the molecular composition of
      human skin. Changes in skin chemistry have been observed in diseases such as
      cancer, psoriasis, eczema, diabetes, and atherosclerosis. Skin chemistry,
      represented by an enormous wealth of disease biomarkers including lipids,
      structural proteins, inflammatory mediators, nucleic acids and small molecules,
      therefore, can serve as a "window to body's health". Various methods including
      tape-stripping, iontophoresis, microneedles and ultrasound, among others, are
      being developed to access skin biomarkers and understand skin's detailed
      molecular composition. This information provides opportunities to diagnose
      various diseases and their response to therapeutic treatments. This review
      provides an overview of such diagnostic and theranostic opportunities. 

PMID- 23159446
TI  - Endophthalmitis after intravitreal injections administered in office.

PMID- 23159447
TI  - Long-term visual acuity and the duration of macular detachment: findings from a
      prospective population-based study.
AB  - AIM: To report the long-term visual outcome of a multicentre prospectively
      recruited cohort of macula-off rhegmatogenous retinal detachments (RRD)  
      METHODS:  The Scottish retinal detachment study was a prospectively recruited
      study that recruited all incident cases of primary RRD in Scotland over a 2-year
      period (2007-2009). All patients with a macula-off RRD from four participating
      sites were invited for clinical examination at 6 weeks, 3 months, 6 months and 1
      year after the initial surgery. Using a joinpoint model we estimated the effect
      of duration of macular detachment on final visual outcome. RESULTS: In total,
      there were 291 patients with macula-off RRD without pre-existing retinal disease
      who had successful repair after one operation. 65.9% achieved a final visual
      acuity (VA) of 0.48 logMAR(6/18). Our model identified two time points (day 8
      (95% CI 3 to 15 days) and (day 21 (95% CI 6 to 26 days)) after which there was a
      statistically significant worsening in final VA. CONCLUSIONS: Our study suggests
      that the majority of patients with macula-off RRD successfully repaired with one
      operation will achieve a VA of 6/18 or better at final follow-up. After 8 days of
      macular detachment, the final visual outcome may be adversely affected and, thus,
      operative repair within this period is desirable. Duration of macular detachment
      of <=8 days demonstrated a continuing improvement in VA for up to 1 year, a
      finding which was not found in macula detachments of longer duration.

PMID- 23159448
TI  - MRI in the detection of hepatic metastases from high-risk uveal melanoma: a
      prospective study in 188 patients.
AB  - BACKGROUND/AIMS: To evaluate MRI in the detection of asymptomatic hepatic
      metastases from uveal melanoma. METHODS: A single-arm prospective cohort study.
      PARTICIPANTS: We enrolled 188 patients whose predicted 5-year mortality from
      uveal melanoma exceeded 50%. This prognostication was performed by multivariate
      analysis of clinical stage, histological grade and genetic type, using our online
      tool, based on Accelerated Failure Time modelling. These high-risk patients
      underwent a six-monthly assessment, which included history-taking, clinical
      examination, hepatic MRI (without contrast, unless suspicious lesions were
      identified) and biochemical liver function tests. RESULTS: Ninety (48%) of the
      188 patients developed detectable metastases, a median of 18 months after ocular
      treatment. Six-monthly MRI-detected metastases before symptoms in 83 (92%) of 90
      patients developing systemic disease, with 49% of these having less than five
      hepatic lesions all measuring less than 2 cm in diameter. Of these 90 patients,
      12 (14%) underwent hepatic resection, all surviving for at least a year
      afterwards. CONCLUSIONS: Six-monthly MRI detects metastases from high-risk uveal
      melanoma before the onset of symptoms, enhancing any opportunities for early
      treatment of metastatic disease and clinical trial participation. Whether these
      actually result in prolongation of life, after taking lead-time bias into
      account, requires further investigation.

PMID- 23159449
TI  - Weight-independent effects of roux-en-Y gastric bypass on glucose homeostasis via
      melanocortin-4 receptors in mice and humans.
AB  - BACKGROUND & AIMS: Roux-en-Y gastric bypass (RYGB) improves glucose homeostasis
      independently of changes in body weight by unknown mechanisms. Melanocortin-4
      receptors (MC4R) have weight-independent effects on glucose homeostasis, via
      autonomic neurons, and also might contribute to weight loss after RYGB. We
      investigated whether MC4Rs mediate effects of RYGB, such as its weight
      independent effects on glucose homeostasis, in mice and humans. METHODS: We
      studied C57BL/6 mice with diet-induced obesity, MC4R-deficient mice, and mice
      that re-express MC4R specifically in autonomic neurons after RYGB or sham
      surgeries. We also sequenced the MC4R locus in patients undergoing RYGB to
      investigate diabetes resolution in carriers of rare MC4R variants. RESULTS: MC4Rs
      in autonomic brainstem neurons (including the parasympathetic dorsal motor vagus)
      mediated improved glucose homeostasis independent of changes in body weight. In
      contrast, MC4Rs in cholinergic preganglionic motor neurons (sympathetic and
      parasympathetic) mediated RYGB-induced increased energy expenditure and weight
      loss. Increased energy expenditure after RYGB is the predominant mechanism of
      weight loss and confers resistance to weight gain from a high-fat diet, the
      effects of which are MC4R-dependent. MC4R-dependent effects of RYGB still
      occurred in mice with Mc4r haplosufficiency, and early stage diabetes resolved at
      a similar rate in patients with rare variants of MC4R and noncarriers. However,
      carriers of MC4R (I251L), a rare variant associated with increased weight loss
      after RYGB and increased basal activity in vitro, were more likely to have early
      and weight-independent resolution of diabetes than noncarriers, indicating a role
      for MC4Rs in the effects of RYGB. CONCLUSIONS: MC4Rs in autonomic neurons mediate
      beneficial effects of RYGB, including weight-independent improved glucose
      homeostasis, in mice and humans.

PMID- 23159450
TI  - Advances in acute and chronic pancreatitis: from development to inflammation and
      repair.

PMID- 23159451
TI  - Glucagon-like peptide-2 stimulates mucosal microcirculation measured by laser
      Doppler flowmetry in end-jejunostomy short bowel syndrome patients.
AB  - BACKGROUND: In animal and human studies glucagon-like peptide-2 (GLP-2) has been
      shown to increase blood flow in the superior mesenteric artery and the portal
      vein. This study describes the effect of GLP-2 measured directly on the
      intestinal mucosal blood flow by laser Doppler flowmetry (LDF) in end-jejunostomy
      short bowel syndrome (SBS) patients. METHODS: In five SBS patients with end
      jejunostomy a specially designed laser Doppler probe was inserted into the stoma
      nipple, and blood flow measured directly on the jejunal mucosa for 105 min in
      relation to no treatment, systemic saline infusion, topical adrenaline
      application and a subcutaneous injection of 800 MUg native GLP-2. RESULTS: The
      GLP-2 injection increased jejunal mucosal blood flow by 79+/-37% compared to
      conditions, where no treatment was given (p<0.001). The significant effect was
      present at least 105 min. Systemic saline infusion and topical, mucosal
      adrenaline application did not affect mucosal microcirculation. CONCLUSIONS: GLP
      2 raises jejunal microcirculation in SBS patients with end-jejunostomy. This may
      explain the redness and increase in the end-jejunostomy nipple size imminently
      after commencing GLP-2 injections. The potential beneficial effects of this GLP-2
      mediated increase of blood flow in the mesenteric bed should be investigated in
      clinical conditions other than the short bowel syndrome.

PMID- 23159452
TI  - Active surveillance for low-risk prostate cancer worldwide: the PRIAS study.
AB  - BACKGROUND: Overdiagnosis and subsequent overtreatment are important side effects
      of screening for, and early detection of, prostate cancer (PCa). Active
      surveillance (AS) is of growing interest as an alternative to radical treatment
      of low-risk PCa. OBJECTIVE: To update our experience in the largest worldwide
      prospective AS cohort. DESIGN, SETTING, AND PARTICIPANTS: Eligible patients had
      clinical stage T1/T2 PCa, prostate-specific antigen (PSA) <= 10 ng/ml, PSA
      density <0.2 ng/ml per milliliter, one or two positive biopsy cores, and Gleason
      score <= 6. PSA was measured every 3-6 mo, and volume-based repeat biopsies were
      scheduled after 1, 4, and 7 yr. Reclassification was defined as more than two
      positive cores or Gleason >6 at repeat biopsy. Recommendation for treatment was
      triggered in case of PSA doubling time <3 yr or reclassification. OUTCOME
      MEASUREMENTS AND STATISTICAL ANALYSIS: Multivariate regression analysis was used
      to evaluate predictors for reclassification at repeat biopsy. Active therapy-free
      survival (ATFS) was assessed with a Kaplan-Meier analysis, and Cox regression was
      used to evaluate the association of clinical characteristics with active therapy
      over time. RESULTS AND LIMITATIONS: In total, 2494 patients were included and
      followed for a median of 1.6 yr. One or more repeat biopsies were performed in
      1480 men, of whom 415 men (28%) showed reclassification. Compliance with the
      first repeat biopsy was estimated to be 81%. During follow-up, 527 patients
      (21.1%) underwent active therapy. ATFS at 2 yr was 77.3%. The strongest
      predictors for reclassification and switching to deferred treatment were the
      number of positive cores (two cores compared with one core) and PSA density. The
      disease-specific survival rate was 100%. Follow-up was too short to draw
      definitive conclusions about the safety of AS. CONCLUSIONS: Our short-term data
      support AS as a feasible strategy to reduce overtreatment. Clinical
      characteristics and PSA kinetics during follow-up can be used for risk
      stratification. Strict monitoring is even more essential in men with high-risk
      features to enable timely recognition of potentially aggressive disease and offer
      curative intervention. Limitations of using surrogate end points and markers in
      AS should be recognized. TRIAL REGISTRATION: The current program is registered at
      the Dutch Trial Register with ID NTR1718
      (http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=1718).

PMID- 23159453
TI  - Reply from authors re: Brian R. Matlaga. How do we manage infected, obstructed
      hydronephrosis? Eur Urol 2013;64:93-4: the infected upper urinary tract stone and
      obstruction: stent first where possible?

PMID- 23159454
TI  - Real-time magnetic resonance-guided high-intensity focused ultrasound focal
      therapy for localised prostate cancer: preliminary experience.
AB  - Five patients with unifocal, biopsy-proven prostate cancer (PCa) evident on
      multiparametric magnetic resonance imaging (MRI) were treated with magnetic
      resonance-guided focused ultrasound (MRgFUS) ablation before radical
      prostatectomy (RP). An endorectal probe featuring a phased-array focused
      ultrasound transducer was positioned for lesion ablation under MRI guidance. The
      tissue temperature and accumulation of thermal damage in the target zone was
      monitored during the procedure by MRI thermometry. Overlap between the ablation
      area and the devascularisation of the target lesion was evaluated by contrast
      enhanced MRI performed immediately after treatment. The procedure was uneventful,
      and no adverse events were observed. RP was safely performed without significant
      surgical difficulties in relation to the previous MRgFUS treatment. The
      histopathology report showed extensive coagulative necrosis, with no residual
      tumour in the ablated area. Significant bilateral residual tumour, not evident on
      pretreatment MRI, was observed outside the treated area in two patients. MRgFUS
      ablation of focal localised PCa is feasible and, if confirmed in appropriate
      studies, could represent a valid option for the focal treatment of localised PCa.

PMID- 23159455
TI  - Reply from authors re: Martin Spahn, Steven Joniau. Positive surgical margin at
      radical prostatectomy: futile or surgeon-dependent predictor of prostate cancer
      death? Eur Urol 2013;64:26-8: adjuvant versus salvage radiotherapy in patients
      with positive surgical margins at radical prostatectomy: that is the question.

PMID- 23159456
TI  - Multiple platforms of a HIV-2 derived lentiviral vector for expanded utility.
AB  - Using the Indian Human immunodeficiency virus type 2 (HIV-2) isolate derived
      lentiviral vector (LV) system reported earlier, we have derived multiple
      differently configured transfer vectors. Among the features imparted, the novel
      ones include a blue/white colony screening platform, a shorter vector backbone
      candidate and availability of default dual tags. Simultaneously, panels with
      different utilities were also made using this LV. These include neomycin or
      puromycin or hygromycin selection markers, with options of default promoter, dual
      multiple cloning site (MCS) availability and drug inducible transgene expression.
      All the transfer vectors contain the main MCS with the option of single step sub
      cloning of a PCR amplified transgene cassette by T/A cloning strategy apart from
      cohesive and blunt end cloning sites, as described for the original parent
      vector. Each transfer vector format was tested by appropriate transgene
      expression function by transduction of target cells. This is the most
      comprehensive HIV-2 based lentiviral vector system developed so far and it will
      significantly aid in preferential applications and thus increase its utility as a
      versatile system for gene transfer technology.

PMID- 23159457
TI  - Obesity as an independent predictor of subjective excessive daytime sleepiness.
AB  - INTRODUCTION: Sleepiness is one of the cardinal complaints of patients in
      tertiary referral centres for sleep disorders. It is commonly associated with
      sleep disorders, but the additional influence of obesity remains unclear. We
      hypothesised that obesity may be an independent predictor of sleepiness in this
      population. PATIENTS AND METHODS: We reviewed 335 patients undergoing overnight
      polysomnography over a 3 month period (May-July 2011), recording selected sleep
      parameters in addition to subjective sleepiness as measured by the Epworth
      Sleepiness Scale (ESS, 0-24 points). RESULTS: 173 patients (120 male, age 52 (13)
      years, BMI 33.9 (7.4) kg/m(2)) had obstructive sleep apnoea and 59 of those were
      established on continuous positive airway pressure (CPAP). 55 patients (38 male,
      age 56 (14) years, BMI 31.7 (6.7) kg/m(2)) had PLM disorder, with 3 on medical
      treatment. 155 patients were obese (93 male, age 50 (14) years, BMI 37.3 (6.1)
      kg/m(2)) and this group was significantly sleepier than the 180 non-obese
      subjects (107 male, age 42 (15) years, BMI 25.3 (3.0) kg/m(2)). The mean ESS of
      the obese group was 12.9 (5.5) points, compared to 10.4 (5.7) points for the non
      obese patients (p < 0.001). Those with a diagnosis of OSA had an ESS of 12.3
      (5.8) versus 10.7 (5.7) points for those without (p = 0.007). Females had an ESS
      of 12.8 (5.9) compared to 10.7 (5.5) points for male patients (p < 0.001).
      Regression analysis revealed that obesity (p = 0.007), PLM disorder (p = 0.010)
      and hypertension (p = 0.032) were independently associated with subjective
      sleepiness (adjusted R(2) = 0.384, p = 0.02), obesity accounting for 15.7% of the
      variability in sleepiness. CONCLUSION: Independent of underlying sleep disorders,
      obesity contributes significantly to daytime sleepiness. Measures to promote
      weight loss and close links to a dietician assisted service will be helpful in
      the specialist setting of a sleep disorders service to improve long-term health
      outcomes.

PMID- 23159459
TI  - Varicella infection in infants less than 12 months.

PMID- 23159458
TI  - Waning immunity to measles in young adults and booster effects of revaccination
      in secondary school students.
AB  - The increasing proportions of adult cases were observed in the recent measles
      outbreaks in Zhejiang Province, China. In order to identify the high-risk age
      groups of measles for targeted intervention, a seroprevalence survey of measles
      antibody was conducted among 1961 participants aged 0-60 years randomly selected
      by age-stratified purpose sampling, and the effect of revaccination program in
      secondary school was evaluated in Zhejiang Province. The adjusted overall
      seropositivity rate of measles was 88% (95% confidence interval [CI]: 86-89%)
      with geometric mean titers (GMT), 976+/-86 mIU/ml. The seropositivity rate of
      measles was significantly lower in subjects aged 15-19 years than aged 5-9 years
      (90% vs 96%, chi(2)=5.21, p=0.022). Both seropositivity rate and GMT level of
      measles were higher in participants aged 10-14 years with >=2 doses MCV than
      those with only 1 dose (95% vs 81%, 1276 mIU/ml vs 666 mIU/ml). The
      seropositivity rate increased from 91% to 100% after revaccination with MCV among
      184 secondary school students. The proportions of measles cases aged >=15 years
      were reduced gradually (chi(2)=55.47, p=0.000) from 2009 to 2011 after
      implementing the revaccination campaign on secondary school students since 2008.
      Our findings strongly suggested that a revaccination opportunity with MCV for
      adolescents helps to improve the population immunity, and it can be conducted
      effectively and practically in secondary school students.

PMID- 23159460
TI  - Bluetongue virus serotype 8 virus-like particles protect sheep against virulent
      virus infection as a single or multi-serotype cocktail immunogen.
AB  - Since 1998, there have been multiple separate outbreaks of Bluetongue disease
      (BT) in Europe with the largest outbreak ever recorded in Northern Europe caused
      by Bluetongue virus serotype 8 (BTV-8). Coinciding with the BTV-8 outbreak, a
      virulent strain of BTV-1 emerged and co-infections of these two serotypes were
      reported. In response, we generated VLPs for BTV-8 and tested the efficacy of BTV
      8 VLPs as a single immunogen and as a component of a multivalent vaccine, with
      VLPs of BTV-1 and BTV-2, in order to test if there was any interference between
      serotypes. All pre-Alps sheep vaccinated with BTV-8 VLPs developed a strong
      neutralising antibody response to BTV-8 and multivalent VLP vaccinated animals
      also developed neutralising antibodies to BTV-1 and BTV-2. There were no side
      effects observed due to the vaccination with either the single- or multivalent
      VLP cocktail. All VLP-vaccinated animals had no clinical manifestation of BT or
      viraemia after challenge with a virulent BTV-8 isolate. This data indicates that
      BTV-8 VLPs delivered as a single immunogen or as a component of a multivalent
      vaccine are highly efficacious. Moreover, there was no interference on the
      development of a strong protective immune response due to the combination of
      different phylogenetically unrelated BTV serotypes in the vaccinated animals.
      This report further highlights that BTV VLPs are safe and efficacious immunogens
      that are able to afford complete protection against a virulent virus challenge.

PMID- 23159461
TI  - Uric acid levels correlate with baseline renal function and high levels are a
      potent risk factor for postoperative chronic kidney disease in patients with
      renal cell carcinoma.
AB  - PURPOSE: We investigated the relationship between preoperative uric acid and the
      glomerular filtration rate preoperatively and postoperatively in patients with
      renal cell carcinoma. MATERIALS AND METHODS: Included in study were 1,534
      patients who underwent radical or partial nephrectomy for renal cell carcinoma
      between 1994 and 2008. Uric acid was measured preoperatively. The estimated
      glomerular filtration rate was calculated using the MDRD (Modification of Diet in
      Renal Disease) equation preoperatively and postoperatively within 7 days, and at
      3 months, and 1 and 3 years. We looked for correlations of uric acid with the
      glomerular filtration rate, patient demographics and comorbidities. We also
      evaluated the predictive value of uric acid for the preoperative glomerular
      filtration rate and new onset chronic kidney disease, defined as a glomerular
      filtration rate of less than 60 ml/minute/1.73 m(2), after nephrectomy using
      multivariate regression analysis. RESULTS: Mean +/- SD uric acid was 5.2 +/- 1.5
      mg/dl (range 1.3 to 11.3). Mean preoperative uric acid correlated with the
      preoperative glomerular filtration rate (r = -0.313, p <0.001) and was associated
      with prevalent chronic kidney disease. On multivariate regression analysis a
      decreased preoperative glomerular filtration rate correlated significantly with
      earlier year of surgery, older age, male gender, hypertension, high uric acid and
      larger tumors (each p <0.001). Hypertension, male gender and high body mass index
      correlated with high uric acid (each p <0.001). Older age (p <0.001), diabetes
      mellitus (p = 0.002), low preoperative glomerular filtration rate (p <0.001) and
      high preoperative uric acid (p = 0.002) were significant predictors of new onset
      chronic kidney disease 3 years after nephrectomy. CONCLUSIONS: Increased
      preoperative uric acid was an independent predictor of a low preoperative
      glomerular filtration rate and new onset chronic kidney disease in patients with
      renal cell carcinoma who underwent nephrectomy.

PMID- 23159462
TI  - Association between warm ischemia time and renal parenchymal atrophy after
      partial nephrectomy.
AB  - PURPOSE: Renal parenchymal volume decrease after partial nephrectomy is
      associated with late functional outcomes. We examined the relative effects of
      resection related and atrophy related volume change on late kidney function.
      MATERIALS AND METHODS: Data were analyzed from a cohort of 187 patients who
      underwent open, laparoscopic or robotic partial nephrectomy between 2009 and
      2011. Total change in kidney size after surgery was expressed as percent
      functional volume preservation measured using the cylindrical volume ratio
      method. Renal atrophy was expressed as parenchymal thickness preservation, and
      was assessed by measuring parenchymal thickness before and after partial
      nephrectomy in regions of the operated kidney distant from the site of resection.
      Standard statistical analyses were conducted to assess relationships among
      variables. RESULTS: Mean (+/- SD) percent functional volume preservation was 92%
      (+/- 8%), which correlated with a late percent glomerular filtration rate
      preservation of 91% (+/- 12%). Mean parenchymal thickness preservation for the
      cohort was 99% (+/- 4%). Minimal atrophy was observed in patients with warm
      ischemia time less than 40 minutes (parenchymal thickness preservation range 98%
      to 100%). Atrophy was more pronounced in patients with warm ischemia time greater
      than 40 minutes (parenchymal thickness preservation 96%). Multivariate regression
      analysis showed correlation of percent functional volume preservation with
      atrophy; correlation of warm ischemia time, diameter-axial-polar nephrometry
      score and atrophy with percent functional volume preservation; and correlation of
      Charlson score and diameter-axial-polar nephrometry score with percent decrease
      in glomerular filtration rate. CONCLUSIONS: In most patients with warm ischemia
      time less than 40 minutes the incidence of parenchymal atrophy was minimal,
      suggesting that the kidney volume decrease after partial nephrectomy was
      predominantly resection related. Kidney volume decrease after partial nephrectomy
      in patients with warm ischemia time greater than 40 minutes appeared to be due to
      a combination of resection related and atrophy related changes.

PMID- 23159463
TI  - Genetic sequence variants are associated with severity of lower urinary tract
      symptoms and prostate cancer susceptibility.
AB  - PURPOSE: While a clear heritable component underlies lower urinary tract symptoms
      and benign prostatic hyperplasia, few studies have identified specific genetic
      factors. In contrast, recent genome-wide association studies identified single
      nucleotide polymorphisms that increase prostate cancer risk. Some of these single
      nucleotide polymorphisms may also predispose to surgical intervention for benign
      prostatic hyperplasia. We determined whether these single nucleotide
      polymorphisms are also associated with lower urinary tract symptom severity and
      benign prostatic hyperplasia medication use. MATERIALS AND METHODS: The genotypes
      of 38 single nucleotide polymorphisms previously associated with prostate cancer
      risk were determined for 1,168 healthy white male volunteers. American Urological
      Association symptom index score and medication for benign prostatic hyperplasia
      were documented prospectively. Statistical analyses were done to compare the
      frequency of the single nucleotide polymorphisms with American Urological
      Association symptom index and benign prostatic hyperplasia medication use.
      RESULTS: Several single nucleotide polymorphisms, including rs2736098 on
      chromosome 5p15, showed a significant relationship with benign prostatic
      hyperplasia medication. After adjusting for the other genetic variants, patient
      age and medication use, rs1571801 on chromosome 9q33.2 (OR 1.31, 95% CI 1.0-1.74)
      and rs5945572 on chromosome Xp11 (OR 1.28, 95% CI 1.04-1.59) were significantly
      associated with increased urinary symptoms. In contrast, rs445114 on chromosome
      8q24 was marginally associated with decreased urinary symptoms (OR 0.83, 95% CI
      0.66-1.01). CONCLUSIONS: Of 38 single nucleotide polymorphisms that predispose to
      prostate cancer we identified 3 that are also associated with a well
      characterized lower urinary tract symptom phenotype. These single nucleotide
      polymorphisms may aid in the improved characterization of men with lower urinary
      tract symptoms/benign prostatic hyperplasia.

PMID- 23159464
TI  - Clinical risk factors, bone density and fall history in the prediction of
      incident fracture among men and women.
AB  - The FRAX(tr) algorithm uses clinical risk factors (CRF) and bone mineral density
      (BMD) to predict fracture risk but does not include falls history in the
      calculation. Using results from the Hertfordshire Cohort Study, we examined the
      relative contributions of CRFs, BMD and falls history to fracture prediction. We
      studied 2299 participants at a baseline clinic that included completion of a
      health questionnaire and anthropometric data. A mean of 5.5years later (range 2.9
      8.8years) subjects completed a postal questionnaire detailing fall and fracture
      history. In a subset of 368 men and 407 women, bone densitometry was performed
      using a Hologic QDR 4500 instrument. There was a significantly increased risk of
      fracture in men and women with a previous fracture. A one standard deviation drop
      in femoral neck BMD was associated with a hazards ratio (HR) of incident fracture
      (adjusted for CRFs) of 1.92 (1.04-3.54) and 1.77 (1.16-2.71) in men and women
      respectively. A history of any fall since the age of 45years resulted in an
      unadjusted HR of fracture of 7.31 (3.78-14.14) and 8.56 (4.85-15.13) in men and
      women respectively. In a ROC curve analysis, the predictive capacity
      progressively increased as BMD and previous falls were added into an initial
      model using CRFs alone. Falls history is a further independent risk factor for
      fracture. Falls risk should be taken into consideration when assessing whether or
      not to commence medication for osteoporosis and should also alert the physician
      to the opportunity to target falls risk directly.

PMID- 23159465
TI  - Production and characterization of a bioflocculant produced by Aspergillus
      flavus.
AB  - The production and characterization of a bioflocculant, IH-7, by Aspergillus
      flavus was investigated. About 0.4 g of purified bioflocculant with an average
      molecular weight of 2.574 * 10(4)Da could be obtained from 1L of fermentation
      medium. The bioflocculant mainly consisted of protein (28.5%) and sugar (69.7%),
      including 40% of neutral sugar, 2.48% of uronic acid and 1.8% amino sugar. The
      neutral sugar components are sucrose, lactose, glucose, xylose, galactose,
      mannose and fructose at a molar ratio of 2.4:4.4:4.1:5.8:9.9:0.8:3.1. Fourier
      transform infrared spectroscopy analysis revealed that purified IH-7 contained
      hydroxyl, amide, carboxyl and methoxyl groups. The elemental analysis of purified
      IH-7 showed that the weight fractions of the elements C, H, O, N and S were
      29.9%, 4.8%, 34.7%, 3.3%, and 2.0%, respectively. IH-7 had good flocculating rate
      in kaolin suspension without cation addition and stable over wide range of pH and
      temperature.

PMID- 23159467
TI  - Efficacy of cocktail phage therapy in treating Vibrio cholerae infection in
      rabbit model.
AB  - Ability of a cocktail of five lytic vibriophages to combatting Vibrio cholerae O1
      infection in rabbit model was examined. In one group, rabbits were administered 1
      * 10(8) plaque forming unit of phage cocktail 6 and 12 h prior to the
      administration of V. cholerae O1, while in the other group, same procedure was
      applied 6 and 12 h post infection. It was observed that oral administration of
      the phage cocktail after oral bacterial challenge lowered the shedding of
      bacteria significantly (p < 0.01). In contrast phage treatment prior to bacterial
      challenge had no such effect (p > 0.05). Results suggest that oral administration
      of phage subsequent to V. cholerae challenge could provide a possible means of
      combatting V. cholerae infection.

PMID- 23159468
TI  - Medicinal plant use in two Andean communities located at different altitudes in
      the Bolivar Province, Peru.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: The study documents current medicinal plant
      knowledge and use in two Andean communities and depicts the dynamic nature of
      ethnobotanical relationships by illustrating cultural integration of biomedicine
      and local plant medicine into a complementary system. AIM OF THE STUDY: In order
      to elucidate the importance of medicinal plants, the following research questions
      were addressed: Which position do medicinal plants have in the local health care
      system? Which plants are used medicinally, and do they differ between the
      communities? Is their use supported pharmacologically? MATERIALS AND METHODS:
      Fieldwork was done for seven months in 2010. Semi-structured interviews were
      conducted with 120 informants in Uchumarca and Pusac/San Vicente de Paul, and the
      medicinal plant species mentioned by the informants were vouchered. RESULTS: In
      total, 2776 plant remedy use reports were recorded. Most people in both
      communities know at least some medicinal plants, usually from their parents,
      grandparents, sometimes from books. There are different types of local plant
      specialists, who are consulted above all for the treatment of diseases thought to
      have a magical origin or for recommendations of plants to treat minor diseases.
      Overall, 140 medicinal plants were documented, with a conformity of over 90%
      between the communities. The effective use of the most frequently cited medicinal
      plants is supported by scientific literature. Most uses were reported for the
      treatment of gastrointestinal (17%), nervous (14%), respiratory (14%), urological
      (13%) and dermatological diseases (8%); nervous diseases were more prevalent in
      the mountain community, while dermatological and urological diseases were more
      common in the valley. CONCLUSIONS: People combine medicinal plant use and
      biomedicine depending on the kind of disease, their beliefs, and their economic
      situation. The local use of different available medical resources is reflected by
      the combination of related epistemologies to explain disease causes. Medicinal
      plant use and biomedicine complement each other to form the local health care
      system.

PMID- 23159466
TI  - Cell biology of infection by Legionella pneumophila.
AB  - Professional phagocytes digest internalized microorganisms by actively delivering
      them into the phagolysosomal compartment. Intravacuolar bacterial pathogens have
      evolved a variety of effective strategies to bypass the default pathway of
      phagosomal maturation to create a niche permissive for their survival and
      propagation. Here we discuss recent progress in our understanding of the
      sophisticated mechanisms used by Legionella pneumophila to survive in phagocytes.

PMID- 23159469
TI  - Safety evaluation of main alkaloids from Rhizoma Coptidis.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Rhizoma Coptidis (RC), a widely used traditional
      Chinese medicine, has been used for the treatment of heat-clearing and
      detoxifying, but there is very little information on its safety. AIM OF THE
      STUDY: To provide information on the safety of RC, we evaluated the toxicity of
      the crude RC and RC alkaloids (berberine, coptisine, palmatine and epiberberine)
      including cytotoxicity, acute toxicity in mice and sub-chronic toxicity in rats.
      MATERIALS AND METHODS: The cytotoxicity of RC alkaloids was tested in HepG2 and
      3T3-L1 cells by the MTT assay. The acute toxicity of RC alkaloids was tested in
      mice and the mortality was calculated at the end of experiment. For sub-chronic
      toxicity study, the rats were treated with the RC alkaloids at a dose of 156
      mg/kg/day and RC at a dose of 521 mg/kg/day for 90 days. Mortality, clinical
      signs, body weight changes, organ weights, urinalysis and hematological
      parameters, gross necropsy and histopathology were monitored during the study
      period. RESULTS: The cell assay indicates that the IC(50) values of berberine,
      coptisine, palmatine and epiberberine in HepG2 cells were 48.17, 64.81, 112.80
      and 120.58 MUg/mL, which in 3T3-L1 cells were 41.76, 56.48, 84.32 and 104.18
      MUg/mL, respectively. In the acute toxicity assay, the LD(50) values of four
      alkaloids were 713.57, 852.12, 1533.68 and 1360 mg/kg, respectively. However, in
      the sub-chronic toxicity study, no mortality and morbidity were observed which
      could be related to RC alkaloids and RC treatment. Besides, there was no
      abnormality in clinical signs, body weights, organ weights, urinalysis,
      hematological parameters, gross necropsy and histopathology in any of the animals
      after the oral administration of RC alkaloids and RC. CONCLUSIONS: Taking these
      results together, we came to the conclusion that the toxicity of berberine is the
      maximum and palmatine is the minimal in four RC alkaloids. The currently
      recommended doses of RC alkaloids and RC consumed are relatively safe.

PMID- 23159470
TI  - Reduced system exposures of total rhein and baicalin after combinatory oral
      administration of rhein, baicalin and berberine to beagle dogs and rats.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Rhein (Rh), baicalin (BG) and berberine (Be) are
      important coexisted constituents of San-Huang-Xie-Xin-Tang, which was widely used
      in traditional Chinese medicine for the treatment of gastritis, hypertension,
      gastric bleeding and peptic ulcers, etc. AIM OF THE STUDY: Based on the extensive
      phase II conjugation reactions of polyphenols (Rh and BG) in vivo, the aims of
      the present study were to investigate the effects of combination (Rh, BG and Be)
      on the system exposures of total Rh and BG involving the phase II conjugates
      metabolites and its possible mechanism. MATERIALS AND METHODS: A 3*3 Latin square
      single heavy design was used to investigate the pharmacokinetics influence of
      total Rh and BG after combination of Be by treating plasma samples with beta
      glucuronidase/sulfatase both in beagle dogs and Wistar rats. In vitro and in situ
      experiment models including in situ rat intestinal perfusion, Caco-2 cell
      monolayer transport and small intestinal flora incubation system were used to
      discuss the possible mechanism. RESULTS: The results of pharmacokinetic
      interactions showed that combination significantly reduced the system exposures
      of total Rh and BG. Compared with Rh or BG alone, the mean area under
      concentration-time curves (AUC(0-t)) of total Rh and BG reduced by 31% and 77% in
      beagle dog experiment. In Wistar rat experiment, the AUC(0-t) of total Rh and BG
      reduced by 22% and 21%. Subsequently, the results of in situ rat intestinal
      perfusion and small intestinal flora incubation system tests revealed that
      combination may decrease the absorption and metabolism of BG. However,
      combination could not affect the transport profile of BG across the Caco-2 cell.
      Moreover, combination did not affect the absorption or metabolism profile of Rh
      in all three in situ/in vitro experiments. CONCLUSIONS: It was deduced that the
      possible mechanism of the reduction of the system exposures of total Rh and BG
      was related to that combination decreased the metabolism of BG to B or the phase
      II conjugates of Rh/BG excreted from liver/bile duct to their free aglycones in
      vivo by inhibiting intestinal flora. The potent effects of combination on the
      phase II conjugates of Rh and B in pharmacokinetics, shown in this paper,
      indicated that more attention should be paid to the phase II conjugates
      metabolites of these polyphenols (undergo extensive phase II conjugation
      reactions in vivo) when applied herbal products composed of these coexist
      compounds.

PMID- 23159471
TI  - Antioxidant and anti-inflammatory effects of Urtica pilulifera extracts in type 2
      diabetic rats.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: "Urtica pilulifera has been traditionally used in
      Egyptian system as an herbal remedy to be a diuretic, antiasthmatic, anti
      inflammatory, hypoglycemic, hemostatic, antidandruff and astringent" AIM OF THE
      STUDY: To evaluate the potential effects of ethyl acetate (EA), chloroform
      (CHLOR) and hexane (HEXA) extracts of Urtica piluliferaas oral anti-diabetic
      agents as well as to evaluate their possible anti-oxidant and anti-inflammatory
      effects in type 2 diabetic rat model. MATERIAL AND METHODS: Type 2 diabetes was
      induced by a high fat diet and low dose streptozotocin (STZ). Diabetic adult male
      albino rats were allocated into groups and treated according to the following
      schedule; Pioglitazone HCL (PIO), EA, CHLOR and HEXA extracts of Urtica
      pilulifera at two doses of 250 and 500 mg/kg were used. In addition, a normal
      control group and a diabetic control one were used for comparison. Blood glucose,
      insulin resistance, antioxidant enzymes, 8-hydroxy-2-deoxyguanosine (8-OHdG) as
      well as C-reactive protein and tumor necrosis factor-alpha levels were evaluated.
      RESULTS: EA and CHLOR extracts of Urtica pilulifera exhibited a significant
      hypoglycemia associated with antioxidant and anti-inflammatory effects in
      diabetic rats; however, HEXA extract showed no beneficial effect. These
      activities are responsible, at least partly, for improvements that have been seen
      in hyperglycemia and insulin resistance of diabetic rats. CONCLUSION: Our results
      encourage the traditional use of Urtica pilulifera extract as an antioxidant and
      anti-inflammatory agent as an additional therapy of diabetes.

PMID- 23159472
TI  - Combretum leprosum Mart. (Combretaceae): potential as an antiproliferative and
      anti-inflammatory agent.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Combretum leprosum is a species that is popularly
      used in Brazil as a healing agent to treat skin problems and lesions. In this
      study we investigated the possible potential of this extract to treat
      inflammatory and hyperproliferative skin conditions. MATERIALS AND METHODS:
      Classical models of skin inflammation such as TPA- and croton oil-induced mouse
      ear oedema were applied in order to verify the potential topical anti
      inflammatory activity of the ethanolic extract from flowers of Combretum
      leprosum. RESULTS: Topical application of ethanolic extract promoted a dose
      dependent inhibition of phorbol ester-induced ear oedema, reduced myeloperoxidase
      activity and IL-6 tissue levels with inhibition comparable to dexamethasone
      (positive control). Histological and immunohistochemical analysis revealed that
      ethanolic extract also suppressed cell infiltration. Ethanolic extract altered
      inflammatory parameters on a chronic skin inflammation model induced by repeated
      applications of croton oil, decreasing ear oedema, epidermal hyperproliferation
      and cell infiltration. In addition, immunohistochemical analysis showed that the
      extract decreased PCNA expression on the epidermis. CONCLUSION: Taken together,
      these results suggest that the extract from flowers of Combretum leprosum could
      be considered as a new potential tool for the treatment of several skin
      inflammatory diseases since it reversed the skin inflammatory and
      hyperproliferative process in a very significant manner. Further investigations
      are needed in order to verify the cellular mechanism and safety of Combretum
      leprosum extract.

PMID- 23159473
TI  - Traditional plant use in the National Park of Cilento and Vallo di Diano,
      Campania, Southern, Italy.
AB  - AIM OF STUDY: This paper reports an ethobotanical survey of the traditional uses
      of medicinal and useful plants in an area of the National Park of Cilento and
      Vallo di Diano, Campania, Southern Italy. MATERIALS AND METHODS: This study
      conducted between 2009 and 2011, gathered information on the medicinal plants
      traditionally used in Southern Italy (Campania Region). In all, we interviewed 70
      key informants, whose age ranged between 50 and 85 years. This people belonged to
      families which had strong links with traditional activities of the area. RESULTS:
      The research resulted to the identification of 192 plants belonging to 64
      families. Among the species reported, 86 are used in human medicine, 15 in
      veterinary medicine, 69 as human foods, 18 as animal feed, 61 for domestic and 8
      for agricultural uses. CONCLUSION: A survey of the available literature on
      Southern Italy ethnobotany reveals that some species have been never reported and
      about 10% of cited uses are new. Data obtained show that in the studied area the
      folk use of plants is alive and still derives from daily practice.

PMID- 23159475
TI  - A clinicopathologic study of immunoglobulin G4-related disease of the femoral and
      popliteal arteries in the spectrum of immunoglobulin G4-related periarteritis.
AB  - BACKGROUND: Immunoglobulin (Ig) G4-related disease has recently been recognized
      to occur in the cardiovascular system in the aorta and main branching arteries,
      often manifesting as aneurysms and arteritis/periarteritis. Peripheral arteries
      (the femoral and popliteal arteries) are frequent sites of arteriosclerosis
      obliterans (ASO) and occasionally show aneurysms or arteritis. This study re
      examined peripheral arterial lesions from the standpoint of IgG4-related disease.
      METHODS: The study comprised 104 patients who underwent surgical treatment of
      peripheral arterial lesions, including 30 patients with peripheral arterial
      aneurysms (PAAs) and 74 with ASO. IgG4-related disease was identified on the
      basis of diffuse infiltration of numerous IgG4-positive plasmacytes as revealed
      by immunohistochemical examination. Clinicopathologic features were compared
      between IgG4-related and IgG4-unrelated lesions. RESULTS: IgG4-related disease
      was found in four of the 30 patients with PAAs (13.3%; two in the deep femoral
      artery, two in the popliteal artery) but not in any patients with ASO. IgG4
      related PAA displayed clinicopathologic features resembling those of other IgG4
      related diseases and a characteristic saccular appearance (P = .002).
      CONCLUSIONS: IgG4-related disease was detected in PAA patients but not in ASO
      patients. IgG4-related disease thus represents one potential etiology of aneurysm
      in the peripheral arteries.

PMID- 23159474
TI  - Risk index for predicting perioperative stroke, myocardial infarction, or death
      risk in asymptomatic patients undergoing carotid endarterectomy.
AB  - OBJECTIVE: The latest guidelines recommend performance of carotid endarterectomy
      (CEA) on asymptomatic patients with high-grade carotid stenosis, only if the
      combined perioperative stroke, myocardial infarction (MI), or death risk is <=3%.
      Our objective was to develop and validate a risk index to estimate the combined
      risk of perioperative stroke, MI, or death in asymptomatic patients undergoing
      elective CEA. METHODS: Asymptomatic patients who underwent an elective CEA (n =
      17,692) were identified from the 2005-2010 National Surgical Quality Improvement
      Program, a multicenter, prospective database. Multivariable logistic regression
      analysis was performed with primary outcome of interest being the composite of
      any stroke, MI, or death during the 30-day periprocedural period. Bootstrapping
      was used for internal validation. A risk index was created by assigning weighted
      points to each predictor using the beta-coefficients from the regression
      analysis. RESULTS: Fifty-eight percent of the patients were men with a median age
      of 72 years. Thirty-day incidences of stroke, MI, and death were 0.9% (n = 167),
      0.6% (n = 108), and 0.4% (n = 72), respectively. The combined 30-day stroke, MI,
      or death incidence was 1.8% (n = 324). On multivariable analysis, six independent
      predictors were identified and a risk index created by assigning weighted points
      to each predictor using the beta-coefficients from the regression analysis. The
      predictors included age in years (<60: 0 point; 60-69: -1 point; 70-79: -1 point;
      >=80: 2 points), dyspnea (2 points), chronic obstructive pulmonary disease (3
      points), previous peripheral revascularization or amputation (3 points), recent
      angina within 1 month (4 points), and dependent functional status (5 points).
      Patients were classified as low (<3%), intermediate (3%-6%), or high (>6%) risk
      for combined 30-day stroke, MI, or death, based on a total point score of <4, 4
      7, and >7, respectively. There were 15,249 patients (86.2%) in the low-risk
      category, 2233 (12.6%) in the intermediate-risk category, and 210 (1.2%) in the
      high-risk category. CONCLUSIONS: The validated risk index can help identify
      asymptomatic patients who are at greatest risk for 30-day stroke, MI, and death
      after CEA, thereby aiding patient selection.

PMID- 23159476
TI  - A meta-analysis of endovascular versus surgical reconstruction of femoropopliteal
      arterial disease.
AB  - BACKGROUND: Controversy exists as to the relative merits of surgical and
      endovascular treatment of femoropoliteal arterial disease. METHODS: A systematic
      review of the literature was undertaken to identify studies comparing open
      surgical and percutaneous transluminal methods for the treatment of
      femoropopliteal arterial disease. Outcome data were pooled and combined overall
      effect sizes were calculated using fixed or random effects models. RESULTS: Four
      randomized controlled trials and six observational studies reporting on a total
      of 2817 patients (1387 open, 1430 endovascular) were included. Endovascular
      treatment was accompanied by lower 30-day morbidity (odds ratio [OR], 2.93; 95%
      confidence interval [CI], 1.34-6.41) and higher technical failure (OR, 0.10; 95%
      CI, 0.05-0.22) than bypass surgery, whereas no differences in 30-day mortality
      between the two groups were identified (OR, 0.92; 95% CI, 0.55-1.51). Higher
      primary patency in the surgical treatment arm was found at 1 (OR, 2.42; 95% CI,
      1.37-4.28), 2 (OR, 2.03; 95% CI, 1.20-3.45), and 3 (OR, 1.48; 95% CI, 1.12-1.97)
      years of intervention. Progression to amputation was found to occur more commonly
      in the endovascular group at the end of the second (OR, 0.60; 95% CI, 0.42-0.86)
      and third (OR, 0.55; 95% CI, 0.39-0.77) year of intervention. Higher amputation
      free and overall survival rates were found in the bypass group at 4 years (OR,
      1.31; 95% CI, 1.07-1.61 and OR, 1.29; 95% CI, 1.04-1.61, respectively).
      CONCLUSIONS: High-level evidence demonstrating the superiority of one method over
      the other is lacking. An endovascular-first approach may be advisable in patients
      with significant comorbidity, whereas for fit patients with a longer-term
      perspective a bypass procedure may be offered as a first-line interventional
      treatment.

PMID- 23159477
TI  - The outcome of failed endografts inserted for superficial femoral artery
      occlusive disease.
AB  - OBJECTIVE: Endografts represent a relatively new treatment modality for occlusive
      disease of the superficial femoral artery, with promising results. However,
      endografts may occlude collateral arteries, which may affect outcome in case of
      failure. The purpose of this study was to analyze the clinical outcome of failed
      endografts in patients with superficial femoral artery occlusive disease.
      METHODS: All patients treated with one or more polytetrafluorethylene-covered
      stents between November 2001 and December 2011 were prospectively included in a
      database. Patients with a failure of the endograft were retrospectively analyzed.
      Clinical and hemodynamic parameters were assessed before the initial procedure
      and at the time of failure. Outcome of secondary procedures was analyzed.
      RESULTS: Among the 341 patients who were treated during the study period, 49
      (14.4%) failed during follow-up. Mean (standard deviation) Rutherford category at
      failure did not differ from the category as scored before the initial procedure
      (3.1 [1.3] vs 3.3 [0.6]; P = .33). Forty-three percent of patients (n = 21)
      presented with the same Rutherford category as before the initial procedure, 37%
      (n = 18) with an improved category, and 20% (n = 10) with a deteriorated
      category. The ankle-brachial index was significantly lower at the time of failure
      (0.66 [0.19] vs 0.45 [0.19[; P <.002). Seventy-six percent of patients with a
      failure needed secondary surgery, of which 25% were below knee. The 1-year
      primary, primary-assisted, and secondary patency rates of secondary bypasses were
      55.1%, 62.3%, and 77.7%, respectively. The amputation rate was 4.1% (n = 2).
      CONCLUSIONS: Failure of endografts is not associated with a deterioration in
      clinical state and is related to a low amputation rate. The hypothesis that
      covered stents do not affect options for secondary reconstructions could not be
      confirmed, as 25% of patients with a failure underwent a below-knee bypass.
      Secondary surgical bypasses are correlated with poor patency. The amputation rate
      after failure is low.

PMID- 23159478
TI  - Technique of supraceliac balloon control of the aorta during endovascular repair
      of ruptured abdominal aortic aneurysms.
AB  - Endovascular aneurysm repair is being used increasingly to treat ruptured
      abdominal aortic aneurysms (RAAAs). Approximately 25% of RAAAs undergo complete
      circulatory collapse before or during the procedure. Patient survival depends on
      obtaining and maintaining supraceliac balloon control until the endograft is
      fully deployed. This is accomplished with a sheath-supported compliant balloon
      inserted via the groin contralateral to the side to be used for insertion of the
      endograft main body. After the main body is fully deployed, a second balloon is
      placed within the endograft, and the first balloon is removed so that extension
      limbs can be placed in the contralateral side. A third balloon can be placed via
      the contralateral side and ipsilateral extensions deployed as necessary. This
      technique of supraceliac balloon control is important to achieving good outcomes
      with RAAAs. In addition to minimizing blood loss, this technique minimizes
      visceral ischemia and maintains aortic control until the aneurysm rupture site is
      fully excluded.

PMID- 23159479
TI  - The impact of oxytocin administration and maternal love withdrawal on event
      related potential (ERP) responses to emotional faces with performance feedback.
AB  - This is the first experimental study on the effect of oxytocin administration on
      the neural processing of facial stimuli conducted with female participants that
      uses event-related potentials (ERPs). Using a double-blind, placebo-controlled
      within-subjects design, we studied the effects of 16 IU of intranasal oxytocin on
      ERPs to pictures combining performance feedback with emotional facial expressions
      in 48 female undergraduate students. Participants also reported on the amount of
      love withdrawal they experienced from their mothers. Vertex positive potential
      (VPP) and late positive potential (LPP) amplitudes were more positive after
      oxytocin compared to placebo administration. This suggests that oxytocin
      increased attention to the feedback stimuli (LPP) and enhanced the processing of
      emotional faces (VPP). Oxytocin heightened processing of the happy and disgusted
      faces primarily for those reporting less love withdrawal. Significant
      associations with LPP amplitude suggest that more maternal love withdrawal
      relates to the allocation of attention toward the motivationally relevant
      combination of negative feedback with a disgusted face.

PMID- 23159480
TI  - Women's attractiveness changes with estradiol and progesterone across the
      ovulatory cycle.
AB  - In many species, females are more sexually attractive to males near ovulation.
      Some evidence suggests a similar pattern in humans, but methodological
      limitations prohibit firm conclusions at present, and information on
      physiological mechanisms underlying any such pattern is lacking. In 202 normally
      cycling women, we explored whether women's attractiveness changed over the cycle
      as a function of two likely candidates for mediating these changes: estradiol and
      progesterone. We scheduled women to attend one session during the late follicular
      phase and another during the mid-luteal phase. At each session, facial
      photographs, voice recordings and saliva samples were collected. All photographs
      and voice recordings were subsequently rated by men for attractiveness and by
      women for flirtatiousness and attractiveness to men. Saliva samples were assayed
      for estradiol and progesterone. We found that progesterone and its interaction
      with estradiol negatively predicted vocal attractiveness and overall (facial plus
      vocal) attractiveness to men. Progesterone also negatively predicted women's
      facial attractiveness to men and female-rated facial attractiveness, facial
      flirtatiousness and vocal attractiveness, but not female-rated vocal
      flirtatiousness. These results strongly suggest a pattern of increased
      attractiveness during peak fertility in the menstrual cycle and implicate
      estradiol and progesterone in driving these changes.

PMID- 23159481
TI  - The defensin-lipid interaction: insights on the binding states of the human
      antimicrobial peptide HNP-1 to model bacterial membranes.
AB  - Antimicrobial peptides are an important component of innate immunity and have
      generated considerable interest as a new potential class of natural antibiotics.
      The biological activity of antimicrobial peptides is strongly influenced by
      peptide-membrane interactions. Human Neutrophil Peptide 1 (HNP-1) is a 30
      aminoacid peptide, belonging to the class of alpha-defensins. Many biophysical
      studies have been performed on this peptide to define its mechanism of action.
      Combining spectroscopic and thermodynamic analysis, insights on the interaction
      of the alpha-defensin with POPE:POPG:CL negative charged bilayers are given. The
      binding states of the peptide below and above the threshold concentration have
      been analyzed showing that the interaction with lipid bilayers is dependent by
      peptide concentration. These novel results that indicate how affinity and
      biological activities of natural antibiotics are depending by their
      concentration, might open new way of investigation of the antimicrobial mode of
      action.

PMID- 23159482
TI  - Reduced steric hindrance and optimized spatial arrangement of carbohydrate
      ligands in imprinted monolayers for enhanced protein binding.
AB  - Imprinted monolayers provide several advantages over bulk imprinting methods.
      This is especially important for large templates such as proteins. Concanavalin A
      (Con A)-imprinted binary monolayers consisting of glycolipids with oligo(ethylene
      glycol) (OEG) spacers and zwitterionic phospholipids (DPPC) were constructed and
      investigated. The shorter phosphorylcholine (PC) headgroups with an almost flat
      on orientation in the binary monolayers gave rise to reduced steric hindrance
      favorable to the accommodation of Con A with greater ease and facilitated the
      access of the OEG-linked mannose moieties for enhanced protein binding. Further
      enhanced binding resulted from optimized spatial rearrangement of the glycolipids
      at the air-water interface directed by Con A in the subphase to create bivalent
      binding sites and to minimize steric crowding of neighboring mannose ligands. The
      combination of the exposed carbohydrate ligands from biologically inert surfaces
      and the optimized ligand arrangement is the most reasonable solution to
      enhancement of protein affinity. The bivalent carbohydrate binding sites
      protruding from the imprinted monolayers were created to be complementary to the
      Con A binding pockets. This strategy generates tailor-made surfaces with enhanced
      protein binding and opens the possibility of controlled assembly of intellectual
      biomaterials and preparation of biosensors.

PMID- 23159483
TI  - Effects of surfactin on membrane models displaying lipid phase separation.
AB  - Surfactin, a bacterial amphiphilic lipopeptide is attracting more and more
      attention in view of its bioactive properties which are in relation with its
      ability to interact with lipids of biological membranes. In this work, we
      investigated the effect of surfactin on membrane structure using model of
      membranes, vesicles as well as supported bilayers, presenting coexistence of
      fluid-disordered (DOPC) and gel (DPPC) phases. A range of complementary methods
      was used including AFM, ellipsometry, dynamic light scattering, fluorescence
      measurements of Laurdan, DPH, calcein release, and octadecylrhodamine B
      dequenching. Our findings demonstrated that surfactin concentration is critical
      for its effect on the membrane. The results suggest that the presence of rigid
      domains can play an essential role in the first step of surfactin insertion and
      that surfactin interacts both with the membrane polar heads and the acyl chain
      region. A mechanism for the surfactin lipid membrane interaction, consisting of
      three sequential structural and morphological changes, is proposed. At
      concentrations below the CMC, surfactin inserted at the boundary between gel and
      fluid lipid domains, inhibited phase separation and stiffened the bilayer without
      global morphological change of liposomes. At concentrations close to CMC,
      surfactin solubilized the fluid phospholipid phase and increased order in the
      remainder of the lipid bilayer. At higher surfactin concentrations, both the
      fluid and the rigid bilayer structures were dissolved into mixed micelles and
      other structures presenting a wide size distribution.

PMID- 23159484
TI  - Quinolines: a new hope against inflammation.
AB  - Although a number of anti-inflammatory drugs have been discovered and developed
      to treat diseases associated with acute and chronic inflammation, many anti
      inflammatories cause adverse side effects. The quinoline framework has emerged as
      a new template for the design and identification of novel anti-inflammatory
      agents. These agents are classified based on the number of substituents present
      on the quinoline ring or compounds containing a quinoline ring fused to other
      heterocycles. This review focuses on the discovery of various quinoline
      derivatives as inhibitors of cyclooxygenase (COX), phosphodiesterase 4 (PDE4) and
      tumour necrosis factor-alpha converting enzyme (TACE), along with transient
      receptor potential vanilloid 1 (TRPV1) antagonists.

PMID- 23159485
TI  - HSV-2 vaccine: current state and insights into development of a vaccine that
      targets genital mucosal protection.
AB  - HSV-2 is one of the most prevalent sexually transmitted infections that result in
      significant morbidity and financial burden on health systems around the world.
      Recurrent and asymptomatic re-activation accompanied by viral shedding is common
      among sero-positive individuals, leading to relatively high efficiency of
      transmission. Prophylactic HSV-2 vaccines are the best and cheapest option to
      address the problems associated with HSV-2 infections globally. However, despite
      persistent efforts, the search for an efficacious vaccine for HSV-2 remains
      elusive. In this review, the current state of HSV-2 vaccines and the outcome of
      past human trials are examined. Furthermore, we discuss the evidence and
      strategies from experimental mouse models that have been successful in inducing
      protective immunity in the genital tract against HSV-2, following immunization.
      Future vaccination strategies that focus on induction of robust mucosal immunity
      in the genital tract may hold the key for a successful vaccine against HSV-2.

PMID- 23159486
TI  - Suspension cell culture as a tool for the characterization of class III
      peroxidases in sugarcane.
AB  - Secreted class III peroxidases (EC 1.11.1.7) are implicated in a broad range of
      physiological processes throughout the plant life cycle. However, the unambiguous
      determination of the precise biological role of an individual class III
      peroxidase isoenzyme is still a difficult task due to genetic redundancy and
      broad substrate specificity in vitro. In addition, many difficulties are
      encountered during extraction and analysis of cell wall proteins. Since class III
      peroxidases are also secreted into the apoplast, the use of suspension cell
      cultures can facilitate isolation and functional characterization of individual
      isoforms. Here, we report on the characterization of class III peroxidases
      secreted in the spent medium of sugarcane suspension cell cultures. After
      treatment with specific inducers of cell wall lignification, peroxidases were
      isolated and activities assayed with guaiacol, syringaldazine and coniferyl
      alcohol. Enzymatic activity was not significantly different after treatments,
      regardless of the substrate, with the exception of methyl-jasmonate treatment,
      which led to a decreased guaiacol peroxidase activity. Remarkably, peroxidases
      isolated from the medium were capable of oxidizing syringaldazine, an analog to
      sinapyl alcohol, suggesting that sugarcane cultures can produce peroxidases
      putatively correlated to lignification. A proteomic approach using activity
      staining of 2-DE gels revealed a complex isoperoxidase profile, composed
      predominantly of cationic isoforms. Individual spots were excised and analyzed by
      LC-ESI-Q-TOF and homology-based search against the Sugarcane EST Database
      resulted in the identification of several proteins. Spatio-temporal expression
      pattern of selected genes was determined for validation of identified class III
      peroxidases that were preferentially expressed during sugarcane stem development.

PMID- 23159487
TI  - Cytological and molecular characterization of non-host resistance in Arabidopsis
      thaliana against wheat stripe rust.
AB  - Wheat stripe rust, caused by Puccinia striiformis f. sp. tritici (Pst), is one of
      the most destructive diseases of wheat worldwide. We report the use of the non
      host plant Arabidopsis thaliana to identify the basis of resistance to Pst at the
      cytological and molecular levels. No visible symptoms were observed on
      Arabidopsis leaves inoculated with Pst. Microscopic observations showed that
      significantly reduced numbers of Pst urediospores had successfully achieved
      penetration in Arabidopsis compared with those in wheat. There were significant
      differences in the frequency of stomatal penetration but not in fungal growth
      among different Pst races in Arabidopsis. The fungus failed to successfully form
      haustoria in Arabidopsis and attempted infection induced an active response
      including accumulation of phenolic compounds and callose deposition in plant
      cells. A set of defence-related genes were also up regulated during the Pst
      infection. Compared with wild type plants, increased fungal growth was observed
      in an npr1-1 mutant and in NahG transformed plants, which both are insensitive to
      salicylic acid. However, treatment of Arabidopsis plants with cytochalasin B, an
      inhibitor of actin microfilament polymerization, did not increase susceptibility
      to Pst. Our results demonstrate that Arabidopsis can be used to study mechanisms
      of non-host resistance to wheat stripe rust, and highlight the significance of
      participation of salicylic acid in non-host resistance to rust fungi.

PMID- 23159488
TI  - Bioremediation of uranium-contaminated groundwater: a systems approach to
      subsurface biogeochemistry.
AB  - Adding organic electron donors to stimulate microbial reduction of highly soluble
      U(VI) to less soluble U(IV) is a promising strategy for immobilizing uranium in
      contaminated subsurface environments. Studies suggest that diagnosing the in situ
      physiological status of the subsurface community during uranium bioremediation
      with environmental transcriptomic and proteomic techniques can identify factors
      potentially limiting U(VI) reduction activity. Models which couple genome-scale
      in silico representations of the metabolism of key microbial populations with
      geochemical and hydrological models may be able to predict the outcome of
      bioremediation strategies and aid in the development of new approaches. Concerns
      remain about the long-term stability of sequestered U(IV) minerals and the
      release of co-contaminants associated with Fe(III) oxides, which might be
      overcome through targeted delivery of electrons to select microorganisms using in
      situ electrodes.

PMID- 23159489
TI  - Evidence of adaptive mitral leaflet growth.
AB  - Ischemic mitral regurgitation is mitral insufficiency caused by myocardial
      infarction. Recent studies suggest that mitral leaflets have the potential to
      grow and reduce the degree of regurgitation. Leaflet growth has been associated
      with papillary muscle displacement, but role of annular dilation in leaflet
      growth is unclear. We tested the hypothesis that chronic leaflet stretch, induced
      by papillary muscle tethering and annular dilation, triggers chronic leaflet
      growth. To decipher the mechanisms that drive the growth process, we further
      quantified regional and directional variations of growth. Five adult sheep
      underwent coronary snare and marker placement on the left ventricle, papillary
      muscles, mitral annulus, and mitral leaflet. After eight days, we tightened the
      snares to create inferior myocardial infarction. We recorded marker coordinates
      at baseline, acutely (immediately post-infarction), and chronically (five weeks
      post-infarction). From these coordinates, we calculated acute and chronic changes
      in ventricular, papillary muscle, and annular geometry along with acute and
      chronic leaflet strains. Chronic left ventricular dilation of 17.15% (p<0.001)
      induced chronic posterior papillary muscle displacement of 13.49 mm (p=0.07).
      Chronic mitral annular area, commissural and septal-lateral distances increased
      by 32.50% (p=0.010), 14.11% (p=0.007), and 10.84% (p=0.010). Chronic area,
      circumferential, and radial growth were 15.57%, 5.91%, and 3.58%, with non
      significant regional variations (p=0.868). Our study demonstrates that mechanical
      stretch, induced by annular dilation and papillary muscle tethering, triggers
      mitral leaflet growth. Understanding the mechanisms of leaflet adaptation may
      open new avenues to pharmacologically or surgically manipulate
      mechanotransduction pathways to augment mitral leaflet area and reduce the degree
      of regurgitation.

PMID- 23159490
TI  - Lack of Sir2 increases acetate consumption and decreases extracellular pro-aging
      factors.
AB  - Yeast chronological aging is regarded as a model for aging of mammalian post
      mitotic cells. It refers to changes occurring in stationary phase cells over a
      relatively long period of time. How long these cells can survive in such a non
      dividing state defines the chronological lifespan. Several factors influence cell
      survival including two well known normal by-products of yeast glucose
      fermentation such as ethanol and acetic acid. In fact, the presence in the growth
      medium of these C2 compounds has been shown to limit the chronological lifespan.
      In the chronological aging paradigm, a pro-aging role has also emerged for the
      deacetylase Sir2, the founding member of the Sirtuin family, whose loss of
      function increases the depletion of extracellular ethanol by an unknown
      mechanism. Here, we show that lack of Sir2 strongly influences carbon metabolism.
      In particular, we point out a more efficient acetate utilization which in turn
      may have a stimulatory effect on ethanol catabolism. This correlates with an
      enhanced glyoxylate/gluconeogenic flux which is fuelled by the acetyl-CoA
      produced from the acetate activation. Thus, when growth relies on a respiratory
      metabolism such as that on ethanol or acetate, SIR2 inactivation favors growth.
      Moreover, in the chronological aging paradigm, the increase in the acetate
      metabolism implies that sir2Delta cells avoid acetic acid accumulation in the
      medium and deplete ethanol faster; consequently pro-aging extracellular signals
      are reduced. In addition, an enhanced gluconeogenesis allows replenishment of
      intracellular glucose stores which may be useful for better long-term cell
      survival.

PMID- 23159491
TI  - Palmitoylation of TNF alpha is involved in the regulation of TNF receptor 1
      signalling.
AB  - The pleiotropic pro-inflammatory cytokine tumour necrosis factor alpha (TNF) is
      synthesised as a transmembrane protein that is subject to palmitoylation. In this
      study, the roles of this acylation on TNF-mediated biological effects were
      investigated. We found that the lipid raft partitioning of TNF is regulated by
      its palmitoylation. Furthermore, we demonstrated that this palmitoylation process
      interferes with the cleavage/degradation of TNF intracellular fragments but is
      not involved in the regulation of its ectodomain shedding. Moreover, we found
      that the palmitoylation of TNF hinders the binding of soluble TNF to TNFR1 and
      regulates the integration/retention of TNFR1 into lipid rafts. Finally, we
      demonstrate that the transmembrane forms of wild-type and palmitoylation
      defective TNF interact differently with TNFR1 and regulate NFkappaB activity,
      Erk1/2 phosphorylation and interleukin-6 synthesis differently, strongly
      suggesting that palmitoylation of TNF is involved in the regulation of TNFR1
      signalling. An evidence for the physiological intervention of this regulation is
      provided by the fact that, in macrophages, the binding of endogenous soluble TNF
      to TNFR1 is enhanced by inhibition of palmitoylation. Therefore, our data
      introduce the new concept that palmitoylation of TNF is one of the means by which
      TNF-producing cells regulate their sensitivity to soluble TNF.

PMID- 23159492
TI  - The association between genetic damage in peripheral blood lymphocytes and
      polymorphisms of three glutathione S-transferases in Chinese workers exposed to
      1,3-butadiene.
AB  - 1,3-Butadiene (BD) has been classified as a human carcinogen, group I; however,
      the relationship between polymorphisms of glutathione S-transferases that
      metabolize BD and chromosomal damage is not clear. The present study used sister
      chromatid exchange (SCE) and cytokinesis-block micronucleus (CBMN) assays to
      detect chromosomal damage in peripheral lymphocytes of 44 BD-exposed workers and
      39 non-exposed healthy controls. PCR and PCR-RFLP were employed to detect three
      known glutathione S-transferase polymorphisms GSTT1, GSTM1, and GSTP1
      (Ile105Val). The data demonstrated that the micronucleus (CBMN) frequency in BD
      exposed workers was significantly higher than that in controls (frequency ratio
      (FR)=1.48, 95% CI: 1.14-1.91, P<0.01), and the CBMN frequency was higher in
      workers exposed to higher cumulative BD levels (FR=1.70, 95% CI: 1.28-2.27,
      P<0.01). However, differences in SCE frequency were not observed (FR=1.14, 95%
      CI: 0.81-1.61, P>0.05). Among exposed workers, chromosomal damage was related to
      BD exposure levels (FR=1.35, 95% CI: 1.02-1.80, P<0.05); age, older workers
      exhibited higher MN frequencies than younger workers (FR=1.45, 95% CI: 1.14-1.84,
      P<0.05); and years of work, those with more years of work exhibited higher MN
      frequencies than those with fewer years (FR=1.40, 95% CI: 1.10-1.77, P<0.05).
      Multivariate Poisson regression analysis showed that those who carried GSTM1 (-)
      (FR=1.48, 95% CI: 1.14-1.92) or GSTT1 (-) (FR=1.42, 95% CI: 1.10-1.83) genotypes,
      and especially those who carried both (FR=2.10, 95% CI: 1.43-3.09) exhibited
      significantly higher MN frequencies than those carrying GSTM1 (+), GSTT1 (+)
      genotypes or their combination. The GSTP1 Val genotype did not affect MN
      frequency (P>0.05). Our results suggested that higher levels of BD exposure in
      the workplace resulted in increased chromosomal damage, and that polymorphisms in
      GSTT1 and GSTM1 genes might modulate the genotoxic effects of BD exposure.
      Furthermore, the GSTT1 and GSTM1 polymorphisms exhibited an additive effect.
      Finally, urinary DHBMA was found to provide a biomarker that correlated with
      airborne BD levels.

PMID- 23159493
TI  - Arthroscopic suture-bridge repair for small to medium size supraspinatus tear:
      healing rate and retear pattern.
AB  - PURPOSE: The purpose of the study was to assess the repair site integrity after
      transosseous equivalent/suture-bridge (TOE/SB) repair with the use of magnetic
      resonance imaging (MRI). METHODS: One hundred seven consecutive shoulders with a
      small to medium-size full-thickness supraspinatus tear were repaired
      arthroscopically with use of the TOE/SB technique. There were 64 men and 41
      women, and mean age at the time of surgery was 54.8 years (range, 21 to 74
      years). All patients underwent postoperative MRI and clinical examination. Mean
      follow-up was 16.1 months (range, 12 to 28 months). RESULTS: The mean Constant
      score improved from 54.5 +/- 12.5 points preoperatively to 80 +/- 12.1 points
      postoperatively (P < .0001). The mean pain score improved from 7 +/- 2 points
      preoperatively to 13 +/- 2.5 postoperatively (P < .0001). The mean active forward
      flexion improved from 151 degrees  +/- 37 degrees  preoperatively to 169 degrees 
      +/- 14 degrees  postoperatively (P < .0001). The mean Constant score was 81
      points when repaired tendon had healed and it was 72.6 points when repaired
      tendon was unhealed (P = .02). Smoking status was found to have detrimental
      influence on the tendon healing (P = .04). Postoperative MRI showed a healed
      repair in 96 (89.7%) of 107 shoulders. Among 11 retears, 10 occurred at the
      greater tuberosity and 1 occurred at the musculotendinous junction. CONCLUSIONS:
      Arthroscopic TOE/SB repair of full-thickness supraspinatus tendon led to a
      healing rate of 89.7%. Patients with healed tendons according to MRI had
      significant better functional and subjective outcome. Smoking habit was found to
      be detrimental on healing. Retears occurred mainly at tendon-bone interface at
      the greater tuberosity, whereas medial cuff failure was observed in only one case
      in the mean time of follow-up. LEVEL OF EVIDENCE: Level IV, therapeutic case
      series.

PMID- 23159494
TI  - Scaffold-based repair for cartilage healing: a systematic review and technical
      note.
AB  - PURPOSE: The aim of this systematic review was to address the treatment of
      chondral and osteochondral knee lesions through the use of scaffolds, by showing
      surgical options and results of this scaffold-based repair approach for the
      healing of the articular surface. METHODS: All studies published in English
      addressing cartilage scaffold-based treatment were identified, including those
      that fulfilled the following criteria: (1) Levels I to IV evidence addressing the
      outlined areas of interest, (2) measures of functional or clinical outcome, (3)
      knee cartilage lesions, and (4) minimum of 2 years of follow-up. RESULTS: The
      analysis showed a progressively increasing number of articles per year from 1995
      to February 2012. The number of selected articles was 51, with 40 focusing on 2
      step procedures and 11 focusing on 1-step procedures. The evaluation of evidence
      level showed 3 randomized studies, 10 comparative studies, 33 case series, and 5
      case reports. CONCLUSIONS: Regenerative scaffold-based procedures are emerging as
      a therapeutic option for the treatment of chondral lesions, but well-designed
      studies are lacking. Systematic long-term evaluation of these techniques and
      randomized studies are necessary to confirm the potential of this treatment
      approach, especially compared with the available traditional treatments.
      Different 1-step scaffold-based strategies are emerging to simplify the procedure
      and reduce costs. LEVEL OF EVIDENCE: Level IV, systematic review of Level I to IV
      studies.

PMID- 23159495
TI  - Pairwise antibody footprinting using surface plasmon resonance technology to
      characterize human papillomavirus type 16 virus-like particles with direct anti
      HPV antibody immobilization.
AB  - This paper describes an approach to surface plasmon resonance (SPR) based epitope
      mapping, also referred to as pairwise antibody footprinting, involving the direct
      immobilization of an antigen-specific primary mAb to the surface of an SPR
      interface. This technique offers a more straightforward approach than indirect
      capture (e.g., via rabbit anti-mouse Fc) as it does not require additional steps
      to block the unoccupied immobilized anti-Fc to prevent non-specific antibody
      binding. This is also an alternative to the direct immobilization of an antigen
      of interest, which may cause conformational changes in the antigen or epitope
      degradation upon chemical immobilization, particularly in successive regeneration
      cycles. It is particularly suitable for highly multivalent targets such as virus
      like particles (VLPs). Using this technique, we assessed a panel of eight
      monoclonal antibodies against HPV (human papilloma virus) L1 protein VLPs
      expressed by Saccharomyces cerevisiae. In the antibody epitope screening studies,
      HPV16 L1-directed conformational mAbs were clearly distinguished from the linear
      mAbs and consistent with known epitope information. Additional studies using a
      linear mAb and a conformational mAb demonstrate the practical application of this
      technique for characterizing the result of process changes and the consistency of
      recombinant HPV16 VLPs. The method is readily extensible to other VLPs and VLP
      based vaccines.

PMID- 23159496
TI  - Presentation and AcqKnowledge: an application of software to study human emotions
      and individual differences.
AB  - This work describes an experiment about startle reflex and individual differences
      in personality with the application of the Presentation and AcqKnowledge
      software. First, Presentation was useful for the design of the display and timing
      of a set of pictures from the IAPS (International Affective Picture System) that
      modulated the elicitation of the startle reflex response to an acoustic stimulus.
      Second, the AcqKnowledge program allowed to record and store psychophysiological
      data, while a Java routine helped to transform the output data into a proper data
      disposition better suited to analyze individual differences. The software used in
      psychophysiological experiments is of an utmost importance concerning the design
      and presentation of stimuli, and to the general management of this type of
      information. In this work, we present an example of the use of two computer
      programs that are helpful for the research about the psychophysiological bases of
      individual differences in relation with human personality, even though they are
      extensible to other biomedical areas of interest.

PMID- 23159497
TI  - Role of transcytolemmal water-exchange in magnetic resonance measurements of
      diffuse myocardial fibrosis in hypertensive heart disease.
AB  - BACKGROUND: The myocardial extracellular volume fraction (MECVF) has been used to
      detect diffuse fibrosis. Estimation of MECVF relies on quantification of the T1
      relaxation time after contrast enhancement, which can be sensitive to equilibrium
      transcytolemmal water-exchange. We hypothesized that MECVF, quantified with a
      parsimonious 2-space water-exchange model, correlates positively with the
      connective tissue volume fraction in a rodent model of hypertensive heart
      disease, whereas the widely used analysis based on assuming fast transcytolemmal
      water-exchange could result in a significant underestimate of MECVF. METHODS AND
      RESULTS: Nomega-nitro-L-arginine-methyl-ester (L-NAME) or placebo was
      administered to 22 and 15 wild-type mice, respectively. MECVF was measured at
      baseline and 7-week follow-up by pre- and postcontrast T1 cardiac magnetic
      resonance imaging at 4.7 T, using a 2-space water-exchange model. Connective
      tissue volume fraction was quantified, using Masson trichrome stain. L-NAME
      induced hypertrophy (weight-indexed left-ventricular mass 2.2+/-0.3 versus 4.1+/
      0.4 MUg/g, P<0.001), and increased connective tissue volume fraction (8.6%+/-1.5
      versus 2.58%+/-0.6, P<0.001), were compared with controls. MECVF was higher in L
      NAME-treated animals (0.43+/-0.09 versus 0.26+/-0.03, P<0.001), and correlated
      with connective tissue volume fraction and weight-indexed left-ventricular mass
      (r=0.842 and r=0.737, respectively, both P<0.0001). Neglecting transcytolemmal
      water-exchange caused a significant underestimate of MECVF changes. Ten patients
      with history of hypertension had significantly higher MECVF (0.446+/-0.063)
      compared with healthy controls (0.307+/-0.030, P<0.001). CONCLUSIONS: Cardiac
      magnetic resonance allowed detection of myocardial extracellular matrix expansion
      in a mouse model and in patients with a history of hypertension. Accounting for
      the effects of transcytolemmal water-exchange can result in a substantial
      difference of MECVF, compared with assuming fast transcytolemmal water-exchange.

PMID- 23159498
TI  - Biomedical text mining and its applications in cancer research.
AB  - Cancer is a malignant disease that has caused millions of human deaths. Its study
      has a long history of well over 100years. There have been an enormous number of
      publications on cancer research. This integrated but unstructured biomedical text
      is of great value for cancer diagnostics, treatment, and prevention. The immense
      body and rapid growth of biomedical text on cancer has led to the appearance of a
      large number of text mining techniques aimed at extracting novel knowledge from
      scientific text. Biomedical text mining on cancer research is computationally
      automatic and high-throughput in nature. However, it is error-prone due to the
      complexity of natural language processing. In this review, we introduce the basic
      concepts underlying text mining and examine some frequently used algorithms,
      tools, and data sets, as well as assessing how much these algorithms have been
      utilized. We then discuss the current state-of-the-art text mining applications
      in cancer research and we also provide some resources for cancer text mining.
      With the development of systems biology, researchers tend to understand complex
      biomedical systems from a systems biology viewpoint. Thus, the full utilization
      of text mining to facilitate cancer systems biology research is fast becoming a
      major concern. To address this issue, we describe the general workflow of text
      mining in cancer systems biology and each phase of the workflow. We hope that
      this review can (i) provide a useful overview of the current work of this field;
      (ii) help researchers to choose text mining tools and datasets; and (iii)
      highlight how to apply text mining to assist cancer systems biology research.

PMID- 23159499
TI  - Methods for studying medical device technology and practitioner cognition: the
      case of user-interface issues with infusion pumps.
AB  - PURPOSE: The aims of this study were to investigate how a variety of research
      methods is commonly employed to study technology and practitioner cognition. User
      interface issues with infusion pumps were selected as a case because of its
      relevance to patient safety. METHODS: Starting from a Cognitive Systems
      Engineering perspective, we developed an Impact Flow Diagram showing the
      relationship of computer technology, cognition, practitioner behavior, and system
      failure in the area of medical infusion devices. We subsequently conducted a
      systematic literature review on user-interface issues with infusion pumps,
      categorized the studies in terms of methods employed, and noted the usability
      problems found with particular methods. Next, we assigned usability problems and
      related methods to the levels in the Impact Flow Diagram. RESULTS: Most study
      methods used to find user interface issues with infusion pumps focused on
      observable behavior rather than on how artifacts shape cognition and
      collaboration. A concerted and theory-driven application of these methods when
      testing infusion pumps is lacking in the literature. Detailed analysis of one
      case study provided an illustration of how to apply the Impact Flow Diagram, as
      well as how the scope of analysis may be broadened to include organizational and
      regulatory factors. CONCLUSION: Research methods to uncover use problems with
      technology may be used in many ways, with many different foci. We advocate the
      adoption of an Impact Flow Diagram perspective rather than merely focusing on
      usability issues in isolation. Truly advancing patient safety requires the
      systematic adoption of a systems perspective viewing people and technology as an
      ensemble, also in the design of medical device technology.

PMID- 23159500
TI  - Cosmetics Europe multi-laboratory pre-validation of the EpiOcularTM reconstituted
      human tissue test method for the prediction of eye irritation.
AB  - Cosmetics Europe, The Personal Care Association (known as Colipa before 2012),
      conducted a program of technology transfer and within/between laboratory
      reproducibility of MatTek Corporation's EpiOcularTM Eye Irritation Test (EIT) as
      one of the two human reconstructed tissue test methods. This EIT EpiOcularTM used
      a single exposure period for each chemical and a prediction model based on a cut
      off in relative survival [ <=60%=irritant (I) (GHS categories 2 and 1); >60%=no
      classification (NC)]. Test substance single exposure time was 30 min with a 2-h
      post-exposure incubation for liquids and 90 min with an 18-h post-exposure
      incubation for solids. Tissue viability was determined by tetrazolium dye (MTT)
      reduction. Combinations of 20 coded chemicals were tested in 7 laboratories.
      Standardized laboratory documentation was used by all laboratories. Twenty
      liquids (11 NC/9 I) plus 5 solids (3 NC/2 I) were selected so that both exposure
      regimens could be assessed. Concurrent positive (methyl acetate) and negative
      (water) controls were tested in each trial. In all, 298 independent trials were
      performed and demonstrated 99.7% agreement in prediction (NC/I) across the
      laboratories. Coefficients of variation for the% survival for tissues from each
      treatment group across laboratories were generally low. This protocol has entered
      in 2010 the experimental phase of a formal ECVAM validation program.

PMID- 23159501
TI  - Development of a repeated exposure protocol of human bronchial epithelium in
      vitro to study the long-term effects of atmospheric particles.
AB  - Chronic exposure to atmospheric particles is suspected of exacerbating chronic
      inflammatory respiratory diseases but the underlying mechanisms remain poorly
      understood. An experimental strategy using human bronchial epithelial cells
      (NHBE) known to be one of the main target cells of particles in the lung was
      developed to investigate the long term effects of repeated exposure to particles.
      Primary cultures of NHBE cells were grown at an air-liquid interface and
      subjected to repeated treatments to particles. Fate of particles, pro
      inflammatory response and epithelial differentiation were studied during the 5
      weeks following the final treatment. Ultrastructural observations revealed the
      biopersistence of particles in the bronchial epithelium. The expression of
      cytochrome P450 1A1, was transiently induced, suggesting that organic compounds
      could have been metabolized. The release of GM-CSF and IL-6 (biomarkers of pro
      inflammatory response), was induced by particle treatments and was maintained up
      to 5weeks after treatments. The release of amphiregulin and TGFalpha (Growth
      Factor) was induced after each treatment. The number of cells expressing the
      mucin MUC5AC, a differentiation marker, was increased in particle-exposed
      epithelium. The experimental strategy we developed is suitable for investigating
      in greater depth the long term effects of particles on bronchial epithelial cells
      repeatedly exposed to atmospheric particles in vitro.

PMID- 23159502
TI  - Season linked responses to fine and quasi-ultrafine Milan PM in cultured cells.
AB  - Exposure to urbane airborne particulate matter (PM) is related to the onset and
      exacerbation of cardiovascular and respiratory diseases. The fine (PM1), and
      quasi-ultrafine (PM0.4) Milan particles collected during different seasons have
      been characterised and the biological effects on human epithelial lung A549,
      monocytes THP-1 cells and their co-culture, evaluated and compared with the
      results obtained on the PM10 and PM2.5 fractions. Chemical composition and
      transmission electron microscopy (TEM) analysis of PM0.4 showed that this
      fraction was very similar to PM1 for biological responses and dimension. All the
      winter fractions increased within 1h the level of reactive oxygen species (ROS),
      while only summer PM2.5 had this effect on A549 cells. The phosphorylation of
      H2AX (gammaH2AX), a marker of double strand DNA breaks (DSBs), was increased by
      all the winter fractions on A549 and THP-1 cells while summer PM samples did not
      induced this effect. PM0.4 and PM1 biological effects are partly similar and
      related to the season of sampling, with effects on ROS and DNA damage induced
      only by winter PM fractions. The winter PM damaging effect on DNA correlates with
      the presence of organic compounds.

PMID- 23159503
TI  - Heat-induced reorganization of the structure of photosystem II membranes: role of
      oxygen evolving complex.
AB  - The sensitivity of the green plants' photosystem II (PSII) to high temperatures
      is investigated in PSII enriched membranes and in membranes, from which the
      oxygen evolving complex is removed. Using steady-state 77 K fluorescence and
      resonance Raman spectroscopy we analyze the interdependency between the
      temperature-driven changes in structure and energy distribution in the PSII
      supercomplex. The results show that the heat treatment induces different
      reduction of the 77 K fluorescence emission in both types of investigated
      membranes: (i) an additional considerable decrease of the overall fluorescence
      emission in Tris-washed membranes as compared to the native membranes; (ii) a
      transition point at 42 degrees C(,) observed only in native membranes; (iii) a
      sharp reduction of the PSII core fluorescence in Tris-washed membranes at
      temperatures higher than 50 degrees C; (iv) a 3 nm red-shift of F700 band's
      maximum in Tris-washed membranes already at 20 degrees C and its further shift by
      1 nm at temperature increase. Both treatments intensified their action by
      increasing the aggregation and dissociation of the peripheral light harvesting
      complexes. The oxygen-evolving complex, in addition to its main function to
      produce O(2), increases the thermal stability of PSII core by strengthening the
      connection between the core and the peripheral antenna proteins and by keeping
      their structural integrity.

PMID- 23159504
TI  - Fluorescence investigation of the interaction of 2-(4-fluorophenyl)-1-phenyl-1H
      phenanthro [9,10-d] imidazole with bovine serum albumin.
AB  - The interaction between 2-(4-fluorophenyl)-1-phenyl-1H-phenanthro [9,10-d]
      imidazole (FPPI) and bovine serum albumin (BSA) was investigated by fluorescence
      spectral studies. The observed experimental result shows that the imidazole
      derivative has strong ability to quench the fluorescence of BSA by forming
      complex which is stabilized by electrostatic interactions. The effective
      quenching constants (K(sv)) were 2.78 * 10(4), 2.52 * 10(4), and 2.32 * 10(4) at
      301, 310, and 318 K respectively. The Stern-Volmer quenching constant (K(sv)),
      binding site number (n), apparent binding constant (K(A)) and corresponding
      thermodynamic parameters (DeltaG, DeltaH, and DeltaS) were calculated. The
      distance between the donor (BSA) and acceptor (FPPI) was obtained according to
      fluorescence resonance energy transfer (FRET). Conformational changes of BSA were
      observed from synchronous fluorescence technique. The effect of metal ions such
      as Cu(2+), Zn(2+), Ca(2+), Mg(2+), Ni(2+), Co(2+), and Fe(2+) on the binding
      constants between the FPPI and BSA were also studied.

PMID- 23159505
TI  - Synthesis, crystal structure, DNA binding and in vitro biological studies of
      Ni(II), Cu(II) and Zn(II) complexes of N-phthaloylglycine.
AB  - Ni(II), Cu(II) and Zn(II) metal complexes of N-phthaloylglycine were synthesized,
      characterized, reported for single crystal X-ray diffraction analysis for Ni(II)
      complex, and investigated for their binding with DNA under physiological
      conditions, using spectroscopic (UV-visible and fluorescence) and hydrodynamic
      techniques. Experimental results from both spectroscopic methods were comparable
      and further supported by viscosity measurements. Binding constant "K(b)" obtained
      from both spectroscopic methods revealed significant binding of compounds with
      DNA via intercalation. Among all compounds comparatively good DNA binding was
      found for Zn(II) complex. Free energies of compounds-DNA interactions indicated
      spontaneity of their binding. Dynamic and bimolecular enhancement values disclose
      static process involved in compounds-DNA complex formation. All compounds
      exhibited broad range antibacterial, while Zn(II) complex exhibited best
      antitumor activity.

PMID- 23159506
TI  - Space-based estimation of the solar UV-B doses for psoriasis heliotherapy in
      Poland using OMI data for the period 2005-2011.
AB  - A UV model is proposed to reconstruct the biologically weighted doses at the
      ground-level, erythemal, vitamin D(3), and antipsoriatic effective doses, based
      on the space data from the Ozone Monitoring Instrument on board of NASA EOS Aura
      spacecraft for the period 2005-2011. The model is training using the results of
      spectral UV measurements carried out at Belsk, Poland. The model outcome is
      verified using the UV spectra measured at Hradec Kralove, Czech Republic. The
      model uncertainty is almost the same for all examined action spectra and
      comparable to that found in earlier studies on differences between the satellite
      overpasses and ground-based erythemal data. Antipsoriatic doses, taken during 2h
      exposure periods near local noon, are reconstructed for selected sites in Poland
      to find if heliotherapy would be an alternative to standard treatment of
      psoriasis by tube irradiation in medical cabinets. Mountain-resort in the
      southern Poland, Zakopane, and rural-site in Central Poland, Belsk, are among the
      best location of potential heliotherapy centers in Poland for late spring/summer
      season. Leba, resort on the Baltic Sea coast, is a potential heliotherapy center
      in June and July. The methodology to disclose possible heliotherapy periods over
      the territory of Poland could be extended to any region. It would help to prepare
      an optimal schedule of antipsoriatic heliotherapy that accounts for local weather
      conditions and medical standards of using UV cabinets.

PMID- 23159507
TI  - Synergistic activity of luteolin and amoxicillin combination against amoxicillin
      resistant Escherichia coli and mode of action.
AB  - The purpose of this research was to investigate whether luteolin has
      antibacterial and synergistic activity against amoxicillin-resistant Escherichia
      coli (AREC) when use singly and in combination with amoxicillin. The primarily
      mode of action is also investigated. The susceptibility assay (minimum inhibitory
      concentration and checkerboard determination) was carried out by the broth
      macrodilution method's in Mueller-Hinton medium. MIC and checkerboard
      determination were carried out after 20 h of incubation at 35 degrees C by
      observing turbidity. The MICs of amoxicillin and luteolin against all AREC
      strains were >1000 and >= 200 MUg/ml respectively. Synergistic activity were
      observed on amoxicillin plus luteolin against these strains. Viable count of this
      combination showed synergistic effect by reducing AREC cell numbers. The results
      indicated that this combination altered both outer and inner membrane
      permeabilisation. Enzyme assay showed that luteolin had an inhibitory activity
      against penicillinase. Fourier Transform-Infrared (FT-IR) spectroscopy exhibited
      that luteolin alone and when combined with amoxicillin caused increase in fatty
      acid and nucleic acid, but decrease in amide I of proteins in bacterial envelops
      compared with control. These results indicated that luteolin has the potential to
      reverse bacterial resistance to amoxicillin in AREC and may operate via three
      mechanisms: inhibition of proteins and peptidoglycan synthesis, inhibition of the
      activity of certain extended-spectrum beta-lactamases and alteration of outer and
      inner membrane permeability. These findings offer the potential to develop a new
      generation of phytopharmaceuticals to treat AREC.

PMID- 23159508
TI  - Clinical and echocardiographic outcomes after implantation of the Trifecta aortic
      bioprosthesis: an initial single-centre experience.
AB  - OBJECTIVES: The Trifecta valve (St. Jude Medical) was introduced into clinical
      practice as a tri-leaflet stented pericardial valve designed for supra-annular
      placement in the aortic position. The present study aims to evaluate the
      preliminary results with this new bioprosthesis. METHODS: Seventy patients
      underwent aortic valve replacement (AVR) with the Trifecta valve between August
      2010 and December 2011. Thirty-three patients were male and 37 were female
      (52.9%). Mean age was 74.65 +/- 7.63 (range 47-90 years). Prevalent cause of AVR
      was aortic stenosis in 64 (91.43%) patients. The mean preoperative pressure
      gradient was 50 +/- 17 (range 20-84 mmHg), and the mean aortic valve area was
      0.77 +/- 0.33. Five (7.14%) patients were operated on due to aortic valve
      endocarditis. One patient was operated on due to isolated, severe aortic
      insufficiency. All patients were in New York Heart Association functional class
      III or IV. Twenty-eight (40%) patients underwent concomitant procedures. RESULTS:
      Concomitant procedures were coronary artery bypass grafting (n = 25), mitral
      valve replacement (n = 1), ablation of atrial fibrillation (n = 1) and septal
      myomectomy (n = 1). There were no intraoperative deaths. The 30-day in-hospital
      mortality was 2.85% (2 of 70). One late death occurred during the in-hospital
      stay due to a multiorgan failure on postoperative day 60. There were 2 (2.85%)
      perioperative strokes. Mean pressure gradient decreased significantly from a
      preoperative value of 50 +/- 17 mmHg to an intraoperative gradient of 9 +/- 4
      mmHg (Table 3). The mean gradients were 14, 11, 11, 8 and 6 mmHg for the 19, 21,
      23, 25 and 27 mm valve size, respectively. No prosthesis dislocation,
      endocarditis, valve thrombosis or relevant aortic regurgitation was observed at
      discharge. CONCLUSIONS: The initial experience with the Trifecta valve
      bioprosthesis shows excellent outcomes with favourable early haemodynamics.
      Further studies with longer follow-up are needed to confirm those preliminary
      results.

PMID- 23159509
TI  - Self-adjustments may account for the contradictory correlations between HRV and
      motion-sickness severity.
AB  - This study investigates the relationship between heart rate variability (HRV) and
      the level of motion sickness (MS) induced by simulated tunnel driving. The HRV
      indices, normalized low frequency (NLF, 0.04-0.15 Hz), normalized high frequency
      (NHF, 0.15-0.4 Hz), and LF/HF ratio were correlated with the subjectively and
      continuously rated MS levels of 20 participants. The experimental results showed
      that for 13 of the subjects, the MS levels positively correlated with the NLF and
      the LF/HF ratio and negatively correlated with the NHF. The remaining seven
      subjects had negative correlations between the MS levels and the NLF and the
      LF/HF ratio and a positive correlation between the MS levels and the NHF. To
      clarify this contradiction, this study also inspected the effects of subjects'
      self-adjustments on the correlations between the MS levels and the HRV indices
      and showed that the variations in the relationship might be attributed to the
      subjects' self-adjustments, which they used to relieve the discomfort of MS.

PMID- 23159510
TI  - Spontaneous closure of intracranial dural arteriovenous fistulas: a report of 3
      cases.
AB  - Spontaneous closures of dural arteriovenous fistulas (dAVFs) are rare. We present
      spontaneous occlusion of dAVFs in 3 cases (one type IIa dAVF, one type IIb and
      one type III). Patients were 3 males with a mean age of 55 years (range 45-61).
      For two patients, the dAVF was revealed by hemorrhage. No head trauma was
      recorded at the interrogatory. Mean delay for spontaneous closure was 4 months (3
      5 months). Review of the literature about this rare occurrence is presented and
      the factors that may lead to spontaneous occlusion of dAVFs are discussed.

PMID- 23159511
TI  - Neuroendoscopic fenestration of the septum pellucidum for monoventricular
      hydrocephalus.
AB  - OBJECTIVES: Monoventricular hydrocephalus (MH) is a rare condition in which the
      site of obstruction is located around one of the interventricular foramen. In
      this paper, the authors offer their experiences in the neuroendoscopic management
      of this uncommon type of hydrocephalus. PATIENTS AND METHODS: The authors
      retrospectively reviewed 12 neuroendoscopic procedures performed between July
      2003 and June 2011 with MH. Clinical and radiological charts were reviewed and
      analysed. RESULTS: The operative course is a simple and successful procedure, and
      the postoperative complaints are mild. The postoperative radiological findings
      showed maintenance of ventricular enlargement in four cases and a significant
      decrease in enlargement in eight patients. However, upon shifting of the septum
      pellucidum, the periventricular transudation disappeared in all patients.
      CONCLUSIONS: Fenestration of the septum pellucidum by neuroendoscope is the best
      treatment for patients with monoventricular hydrocephalus. The approach for
      fenestration of the septum pellucidum is based on the experience of the
      neurosurgeon and the preoperative planning.

PMID- 23159512
TI  - The influence of textile vascular prosthesis crimping on graft longitudinal
      elasticity and flexibility.
AB  - Textile vascular prostheses are the principal substitute for the replacement of
      large vascular arteries. These prostheses undergo a thermal treatment of crimping
      inducing a wavy shape of the graft wall. Today mechanical properties of crimped
      vascular prostheses are not well known. After implantation, vascular prostheses
      are exposed to several longitudinal forces due to blood pressure, inducing their
      deformation during the cardiac cycle. In arteries that undergo large bending
      deformation, the flexibility is a necessary feature of vascular prostheses. In
      the present work, a longitudinal tensile model and a bending model of woven
      vascular prosthesis are numerically simulated. The obtained results provide a
      better understanding of the impact of the crimping parameters on the longitudinal
      elasticity and the bending stiffness of the textile vascular prosthesis.
      Mathematical predictive models of longitudinal elasticity and bending stiffness
      of the textile prosthesis have been developed, allowing relating the prosthesis
      elasticity and flexibility with the crimping parameters.

PMID- 23159513
TI  - Status epilepticus revealing a giant schizencephaly.

PMID- 23159514
TI  - [Sickle cell disease and life-threatening acute chest syndrome: Interest of
      extracorporeal life support].

PMID- 23159515
TI  - [Fiberoptic bronchoscopies under local anesthesia using lidocaine: be careful of
      systemic toxicity].

PMID- 23159516
TI  - [Attempted suicide by intrapulmonary self-injection of White spirit(r)].

PMID- 23159517
TI  - Feasibility of a thoraco-abdominal CT with injection of iodinated contrast agent
      on sternal intraosseous catheter in an emergency department.

PMID- 23159518
TI  - [Proceedings of the 19th day of Anaesthesia Club in ENT].

PMID- 23159519
TI  - Role of Cryptococcus neoformans Rho1 GTPases in the PKC1 signaling pathway in
      response to thermal stress.
AB  - To initiate and establish infection in mammals, the opportunistic fungal pathogen
      Cryptococcus neoformans must survive and thrive upon subjection to host
      temperature. Primary maintenance of cell integrity is controlled through the
      protein kinase C1 (PKC1) signaling pathway, which is regulated by a Rho1 GTPase
      in Saccharomyces cerevisiae. We identified three C. neoformans Rho GTPases, Rho1,
      Rho10, and Rho11, and have begun to elucidate their role in growth and activation
      of the PKC1 pathway in response to thermal stress. Western blot analysis revealed
      that heat shock of wild-type cells resulted in phosphorylation of Mpk1 mitogen
      activated protein kinase (MAPK). Constitutive activation of Rho1 caused
      phosphorylation of Mpk1 independent of temperature, indicating its role in
      pathway regulation. A strain with a deletion of RHO10 also displayed this
      constitutive Mpk1 phosphorylation phenotype, while one with a deletion of RHO11
      yielded phosphorylation similar to that of wild type. Surprisingly, like a
      rho10Delta strain, a strain with a deletion of both RHO10 and RHO11 displayed
      temperature sensitivity but mimicked wild-type phosphorylation, which suggests
      that Rho10 and Rho11 have coordinately regulated functions. Heat shock-induced
      Mpk1 phosphorylation also required the PKC1 pathway kinases Bck1 and Mkk2.
      However, Pkc1, thought to be the major regulatory kinase of the cell integrity
      pathway, was dispensable for this response. Together, our results argue that Rho
      proteins likely interact via downstream components of the PKC1 pathway or by
      alternative pathways to activate the cell integrity pathway in C. neoformans.

PMID- 23159520
TI  - Intracellular trafficking and glycobiology of TbPDI2, a stage-specific protein
      disulfide isomerase in Trypanosoma brucei.
AB  - Trypanosoma brucei protein disulfide isomerase 2 (TbPDI2) is a bloodstream stage
      specific lumenal endoplasmic reticulum (ER) glycoprotein. ER localization is
      dependent on the TbPDI2 C-terminal tetrapeptide (KQDL) and is mediated by TbERD2,
      an orthologue of the yeast ER retrieval receptor. Consistent with this function,
      TbERD2 localizes prominently to ER exit sites, and RNA interference (RNAi)
      knockdown results in specific secretion of a surrogate ER retention reporter,
      BiPN:KQDL. TbPDI2 is highly N-glycosylated and is reactive with tomato lectin,
      suggesting the presence of poly-N-acetyllactosamine modifications, which are
      common on lyso/endosomal proteins in trypanosomes but are inconsistent with ER
      localization. However, TbPDI2 is reactive with tomato lectin immediately
      following biosynthesis-far too rapidly for transport to the Golgi compartment,
      the site of poly-N-acetyllactosamine addition. TbPDI2 also fails to react with
      Erythrina cristagalli lectin, confirming the absence of terminal N
      acetyllactosamine units. We propose that tomato lectin binds the Manbeta1
      4GlcNAcbeta1-4GlcNAc trisaccharide core of paucimannose glycans on both newly
      synthesized and mature TbPDI2. Consistent with this proposal, alpha-mannosidase
      treatment renders oligomannose N-glycans on the T. brucei cathepsin L orthologue
      TbCatL reactive with tomato lectin. These findings resolve contradictory evidence
      on the location and glycobiology of TbPDI2 and provide a cautionary note on the
      use of tomato lectin as a poly-N-acetyllactosamine-specific reagent.

PMID- 23159521
TI  - Hyperfibrinolysis diagnosed by rotational thromboelastometry in a case of
      suspected amniotic fluid embolism.
AB  - Rotational thromboelastometry is a viscoelastomeric, point-of-care method for
      testing haemostasis in whole blood which can be visualised rapidly, in real time,
      in the operating theatre. Advantages over traditional coagulation tests relate to
      the rapid feedback of results and the ability to visualise hyperfibrinolysis. We
      present a case of suspected amniotic fluid embolism that presented with sudden
      respiratory arrest associated with haemodynamic compromise during a non-elective
      caesarean delivery. Soon after the collapse, coagulopathy developed. Rotational
      thromboelastometry showed hyperfibrinolysis and hypofibrinogenaemia, which
      allowed targeted coagulation factor replacement therapy and the use of tranexamic
      acid. Hyperfibrinolysis may be a contributor to the coagulopathy associated with
      amniotic fluid embolism but has been infrequently reported, perhaps due to
      limited diagnosis with traditional coagulation tests. Treatment of the
      coagulopathy associated with a suspected amniotic fluid embolism with
      antifibrinolytic agents may deserve greater consideration.

PMID- 23159522
TI  - Acquired Chiari I malformation: a differential diagnosis in severe postdural
      puncture headache?

PMID- 23159523
TI  - Integrating nutrition and immunology: a new frontier.
AB  - Nutrition is critical to immune defence and parasite resistance, which not only
      affects individual organisms, but also has profound ecological and evolutionary
      consequences. Nutrition and immunity are complex traits that interact via
      multiple direct and indirect pathways, including the direct effects of nutrition
      on host immunity but also indirect effects mediated by the host's microbiota and
      pathogen populations. The challenge remains, however, to capture the complexity
      of the network of interactions that defines nutritional immunology. The aim of
      this paper is to discuss the recent findings in nutritional research in the
      context of immunological studies. By taking examples from the entomological
      literature, we argue that insects provide a powerful tool for examining the
      network of interactions between nutrition and immunity due to their tractability,
      short lifespan and ethical considerations. We describe the relationships between
      dietary composition, immunity, disease and microbiota in insects, and highlight
      the importance of adopting an integrative and multi-dimensional approach to
      nutritional immunology.

PMID- 23159525
TI  - Melanoma cells use Thy-1 (CD90) on endothelial cells for metastasis formation.
AB  - The cell adhesion molecule Thy-1 (CD90) mediates the adhesion of melanoma cells
      to activated human endothelial cells (EC) via the interaction with the
      alphavbeta3-integrin on the tumor cells in vitro. Here, we report a strong
      expression of Thy-1 on both blood vessel and lymphatic EC in melanoma and
      melanoma metastases. Vascular endothelial growth factor and tumor necrosis factor
      alpha were identified as inducers of Thy-1 expression on EC in vitro. The
      physiological role of Thy-1 for lymphogenic and hematogenic metastasis of
      melanoma cells was substantiated in an experimental metastasis model using
      B16/F10 melanoma cells. Mice lacking Thy-1 showed markedly diminished
      experimental lung metastasis after injection of B16/F10 melanoma cells compared
      to wild-type littermate controls. In addition, on generation of a primary
      subcutaneous tumor, metastasis to regional lymph nodes was clearly reduced in Thy
      1(-/-) mice. However, Thy-1 deletion did not affect subcutaneous primary tumor
      growth, tumor-induced recruitment of inflammatory cells or T cells, angiogenesis,
      or T-cell activation. In conclusion, Thy-1 contributes to metastasis of melanoma
      cells by mechanisms likely involving a Thy-1-mediated adhesion of melanoma cells
      to EC.

PMID- 23159524
TI  - Cocaine use reduction with buprenorphine (CURB): rationale, design, and
      methodology.
AB  - BACKGROUND: Effective medications to treat cocaine dependence have not been
      identified. Recent pharmacotherapy trials demonstrate the potential efficacy of
      buprenorphine (BUP) (alone or with naltrexone) for reducing cocaine use. The
      National Institute on Drug Abuse Clinical Trials Network (CTN) launched the
      Cocaine Use Reduction with Buprenorphine (CURB) investigation to examine the
      safety and efficacy of sublingual BUP (as Suboxone(r)) in the presence of
      extended-release injectable naltrexone (XR-NTX, as Vivitrol(r)) for the treatment
      of cocaine dependence. This paper describes the design and rationale for this
      study. METHODS: This multi-site, double-blind, placebo-controlled study will
      randomize 300 participants across 11 sites. Participants must meet the DSM-IV
      criteria for cocaine dependence and past or current opioid dependence or abuse.
      Participants are inducted onto XR-NTX after self-reporting at least 7 days of
      abstinence from opioids and tolerating a naloxone challenge followed by oral
      naltrexone and are then randomly assigned to one of three medication conditions
      (4 mg BUP, 16 mg BUP, or placebo) for 8 weeks. Participants receive a second
      injection of XR-NTX 4 weeks after the initial injection, and follow-up visits are
      scheduled at 1 and 3 months post-treatment. Participants receive weekly cognitive
      behavioral therapy (CBT). Recruitment commenced in September, 2011. Enrollment,
      active medication, and follow-up phases are ongoing, and recruitment is exceeding
      targeted enrollment rates. CONCLUSIONS: This research using 2 medications will
      demonstrate whether BUP, administered in the presence of XR-NTX, reduces cocaine
      use in adults with cocaine dependence and opioid use disorders and will
      demonstrate if XR-NTX prevents development of physiologic dependence on BUP.

PMID- 23159526
TI  - Adaptive immunity and atherosclerosis: mouse tales in the AJP.
AB  - Chronic inflammation driven by immune responses to lipid deposition in the
      arterial wall is now understood to be fundamental to the pathogenesis of
      atherosclerosis. The frequent presence of T lymphocytes in human atherosclerotic
      lesions was first described in the 1980s, but experiments to test whether
      adaptive immunity influences lesion development and phenotype required animal
      models. The American journal of pathology has published many research articles
      focused on the role of inflammation and adaptive immunity in diet-induced and
      genetically manipulated murine models of atherosclerosis. Seminal articles in the
      1990s were the first to describe the presence of T cells in mouse atherosclerotic
      lesions; other articles demonstrated the effects of defective adaptive immunity
      on lesion development in mice.

PMID- 23159527
TI  - A simplified murine intimal hyperplasia model founded on a focal carotid
      stenosis.
AB  - Murine models offer a powerful tool for unraveling the mechanisms of intimal
      hyperplasia and vascular remodeling, although their technical complexity
      increases experimental variability and limits widespread application. We describe
      a simple and clinically relevant mouse model of arterial intimal hyperplasia and
      remodeling. Focal left carotid artery (LCA) stenosis was created by placing 9-0
      nylon suture around the artery using an external 35-gauge mandrel needle (middle
      or distal location), which was then removed. The effect of adjunctive diet
      induced obesity was defined. Flowmetry, wall strain analyses, biomicroscopy, and
      histology were completed. LCA blood flow sharply decreased by ~85%, followed by a
      responsive right carotid artery increase of ~71%. Circumferential strain
      decreased by ~2.1% proximal to the stenosis in both dietary groups. At 28 days,
      morphologic adaptations included proximal LCA intimal hyperplasia, which was
      exacerbated by diet-induced obesity. The proximal and distal LCA underwent
      outward and negative inward remodeling, respectively, in the mid-focal stenosis
      (remodeling indexes, 1.10 and 0.53). A simple, defined common carotid focal
      stenosis yields reproducible murine intimal hyperplasia and substantial
      differentials in arterial wall adaptations. This model offers a tool for
      investigating mechanisms of hemodynamically driven intimal hyperplasia and
      arterial wall remodeling.

PMID- 23159528
TI  - Futility rules for telaprevir combination treatment for patients with hepatitis C
      virus infection.
AB  - For patients treated with telaprevir, peginterferon, and ribavirin, futility
      rules have been developed to prevent needless drug exposure and minimize
      development of drug-resistant variants for patients who have little or no chance
      of achieving a sustained virologic response. We performed retrospective analyses
      of data from phase 3 trials and validated the current futility rule. All therapy
      should be stopped for treatment-naive and treatment-experienced patients if
      hepatitis C virus RNA levels are greater than 1000 IU/mL at weeks 4 or 12, or if
      hepatitis C virus RNA is detectable at week 24.

PMID- 23159529
TI  - Nanobody-albumin nanoparticles (NANAPs) for the delivery of a multikinase
      inhibitor 17864 to EGFR overexpressing tumor cells.
AB  - A novel, EGFR-targeted nanomedicine has been developed in the current study.
      Glutaraldehyde crosslinked albumin nanoparticles with a size of approximately
      100nm were loaded with the multikinase inhibitor 17864-L(x)-a platinum-bound
      sunitinib analogue-which couples the drug to methionine residues of albumin and
      is released in a reductive environment. Albumin nanoparticles were surface-coated
      with bifunctional polyethylene glycol 3500 (PEG) and a nanobody-the single
      variable domain of an antibody-(Ega1) against the epidermal growth factor
      receptor (EGFR). EGa1-PEG functionalized nanoparticles showed a 40-fold higher
      binding to EGFR-positive 14C squamous head and neck cancer cells in comparison to
      PEGylated nanoparticles. 17864-L(x) loaded EGa1-PEG nanoparticles were
      internalized by clathrin-mediated endocytosis and ultimately digested in
      lysosomes. The intracellular routing of EGa1 targeted nanoparticles leads to a
      successful release of the kinase inhibitor in the cell and inhibition of
      proliferation whereas the non-targeted formulations had no antiproliferative
      effects on 14C cells. The drug loaded targeted nanoparticles were as effective as
      the free drug in vitro. These results demonstrate that multikinase inhibitor
      loaded nanoparticles are interesting nanomedicines for the treatment of EGFR
      positive cancers.

PMID- 23159530
TI  - Potential of recombinant flagellin fragment from Burkholderia thailandensis as an
      antigen for melioidosis antibody detection by indirect ELISA.
AB  - Non-pathogenic Burkholderia thailandensis may be used as a model for Burkholderia
      pseudomallei due to the genetic similarity of these species. Moreover, the
      experimental manipulation of B. thailandensis is safer. In this study, we
      constructed recombinant flagellin protein fragments of B. thailandensis E264
      (FLAG300, FLAG600, FLAG900, and FLAGFL fragments) and used fragments as the
      antigen to detect melioidosis antibodies by an indirect enzyme-linked
      immunosorbent assay (indirect ELISA). The serum samples consisted of
      serodiagnostic melioidosis sera (N = 52), septicemic sera caused by other
      bacteria (disease control) (N = 16) and healthy donor sera (N = 40). The area
      under the receiver operating characteristic (ROC) curve at optimal value (mean
      plus standard deviation) of all constructed fragments to melioidosis antibodies
      detection ranged from 0.654 to 0.953. The highest area under the ROC curve
      (AUROCC, 0.953) for FLAG300 fragment at 1600 serum titer revealed the best
      performance of melioidosis diagnosis. The indirect ELISA using this fragment as
      the antigen possessed 82.7% sensitivity and 94.6% specificity.

PMID- 23159532
TI  - Molecular diagnostics of acute myeloid leukemia: it's a (next) generational
      thing.
AB  - This commentary highlights the article by Spencer et al that outlines a novel
      next-generation sequencing-based method for the detection of FLT3 mutations.

PMID- 23159534
TI  - Polyglandular autoimmune syndrome type II.
AB  - The polyglandular autoimmune syndromes (PAS) comprise a wide spectrum of
      autoimmune disorders. There exist a juvenile (PAS I) and an adult type (PAS II).
      The nature of PAS has been based on the presence of lymphocyte infiltration in
      the affected gland, organ-specific antibodies in the serum, cellular immune
      defects and an association with the human leucocyte antigen (HLA) DR/DQ genes or
      immune response genes. Autoantibodies to the various endocrine and non-endocrine
      tissues not only offer a diagnostic clue to the autoimmune nature of diseases but
      also can be used to identify asymptomatic individuals who are at risk of
      developing other component diseases of the syndrome. Although target tissues or
      glands differ, several common threads link the diseases of PAS. A defect resides
      in one of the genes of the HLA locus which, in concert with other gene(s),
      results in susceptibility. Genetic susceptibility is necessary but not sufficient
      to produce the disorder. This is illustrated by the lack of 100% concordance of
      disease in identical twins. Genetic testing may identify patients with PAS I, but
      not those with PAS II. For PAS II, susceptibility genes are known which increase
      the risk for developing autoimmune disorders, but must not be causative. These
      are certain HLA genes, the cytotoxic T-lymphocyte antigen (CTLA-4) gene, and the
      protein tyrosine phosphatase non-receptor type 22 (PTPN22) genes on chromosomes
      6, 2, and 1, respectively. When the genetic defects and environmental influences
      of organ-specific autoimmunity are better understood, it may be possible to
      devise specific replacement or corrective therapies. Given the similar features
      of many of the organ-specific autoimmune disorders, it is likely that if
      immunotherapeutic modalities are successful in one disease, they may be of
      benefit in related disorders.

PMID- 23159533
TI  - Identifying patients with undetected gastro-oesophageal cancer in primary care:
      External validation of QCancer(r) (Gastro-Oesophageal).
AB  - OBJECTIVE: To evaluate the performance of QCancer(r) (Gastro-Oesophageal) for
      predicting the risk of undiagnosed gastro-oesophageal cancer in an independent UK
      cohort of patients from general practice records. DESIGN: Open cohort study to
      validate QCancer(r) (Gastro-Oesophageal) prediction model. Three hundred sixty
      five practices from the United Kingdom contributing to The Health Improvement
      Network database. 2.1 million patients registered with a general practice surgery
      between 01 January 2000 and 30 June 2008, aged 30-84years (3.7 million person
      years) with 1766 gastro-oesophageal cancer cases. The outcome, gastro-oesophageal
      cancer was defined as incident diagnosis of gastro-oesophageal cancer during the
      2years after study entry. RESULTS: The results from this independent and external
      validation of QCancer(r) (Gastro-Oesophageal) demonstrated good performance data
      on a large cohort of general practice patients. QCancer(r) (Gastro-Oesophageal)
      had very good discrimination with c-statistics of 0.93 and 0.94 for women and men
      respectively. QCancer(r) (Gastro-Oesophageal) was well calibrated across all
      tenths of risk and over all age ranges with predicted risks closely matching
      observed risks. QCancer(r) (Gastro-Oesophageal) explained 74.4% and 75.6% of the
      variation in men and women respectively. CONCLUSIONS: QCancer(r) (Gastro
      Oesophageal) is a useful tool to identify undiagnosed gastro-oesophageal cancer
      in primary care in the United Kingdom.

PMID- 23159531
TI  - New insights on neurobiological mechanisms underlying alcohol addiction.
AB  - Alcohol dependence/addiction is mediated by complex neural mechanisms that
      involve multiple brain circuits and neuroadaptive changes in a variety of
      neurotransmitter and neuropeptide systems. Although recent studies have provided
      substantial information on the neurobiological mechanisms that drive alcohol
      drinking behavior, significant challenges remain in understanding how alcohol
      induced neuroadaptations occur and how different neurocircuits and pathways cross
      talk. This review article highlights recent progress in understanding neural
      mechanisms of alcohol addiction from the perspectives of the development and
      maintenance of alcohol dependence. It provides insights on cross talks of
      different mechanisms and reviews the latest studies on metaplasticity, structural
      plasticity, interface of reward and stress pathways, and cross-talk of different
      neural signaling systems involved in binge-like drinking and alcohol dependence.

PMID- 23159535
TI  - [Metformin in type 2 diabetes: what if we get it wrong?].

PMID- 23159536
TI  - [An unusual cause of compressive optic neuropathy].
AB  - Clinical manifestations of hydrocephalus vary according to the level of
      intracranial pressure, the speed of onset, and the etiological mechanism
      involved. We report the case of a 32-year-old patient with isolated compressive
      optic neuropathy associated with a dilated third ventricle, revealing congenital
      hydrocephalus.

PMID- 23159537
TI  - [Corneal manifestations of measles in the unvaccinated adult: two typical cases
      during an epidemic].
AB  - Measles is a disease due to morbillivirus, which belongs to the paramyxoviridae
      subfamily. It affects mostly young patients, and evolves through four phases:
      incubation, invasion, eruption and desquamation. Ophthalmic manifestations may
      occur during the invasive and eruptive phases. Conjunctivitis is the most common
      ophthalmologic manifestation and is often asymptomatic. Measles keratitis is the
      most concerning manifestation, with possible corneal ulcer, bacterial
      superinfection and corneal perforation. We report two cases of acute keratitis
      occurring during the eruptive phase of measles in two unvaccinated young adults.
      The involvement was central and strictly epithelial in both patients. The outcome
      was favorable with symptomatic treatment.

PMID- 23159538
TI  - Unusual binding of Grb2 protein to a bivalent polyproline-ligand immobilized on a
      SPR sensor: intermolecular bivalent binding.
AB  - The Grb2 adapter protein is involved in the activation of the Ras signaling
      pathway. It recruits the Sos protein by binding of its two SH3 domains to Sos
      polyproline sequences. We observed that the binding of Grb2 to a bivalent ligand,
      containing two Sos-derived polyproline-sequences immobilized on a SPR sensor,
      shows unusual kinetic behavior. SPR-kinetic analysis and supporting data from
      other techniques show major contributions of an intermolecular bivalent binding
      mode. Each of the two Grb2 SH3 domains binds to one polyproline-sequence of two
      different ligand molecules, facilitating binding of a second Grb2 molecule to the
      two remaining free polyproline binding sites. A molecular model based on the X
      ray structure of the Grb2 dimer shows that Grb2 is flexible enough to allow this
      binding mode. The results fit with a role of Grb2 in protein aggregation,
      achieving specificity by multivalent interactions, despite the relatively low
      affinity of single SH3 interactions.

PMID- 23159539
TI  - Characterization of the compact bicistronic microRNA precursor, miR-1/miR-133,
      expressed specifically in Ciona muscle tissues.
AB  - Muscle-specific miR-1/206 and miR-133 families have been suggested to play
      fundamental roles in skeletal and cardiac myogenesis in vertebrates. To gain
      insights into the relationships between the divergence of these miRs and muscular
      tissue types, we investigated the expression patterns of miR-1 and miR-133 in two
      ascidian Ciona species and compared their genomic structures with those of other
      chordates. We found that Ciona intestinalis and Ciona savignyi each possess a
      single copy of the miR-1/miR-133 cluster, which is only 350 nucleotide long.
      During embryogenesis, Ciona miR-1 and miR-133 are generated as a single
      continuous primary transcript accumulated in the nuclei of the tail muscle cells,
      starting at the gastrula stage. In adults, mature miR-133 and miR-1 are
      differentially expressed in the heart and body wall muscle. Expression of the
      reporter gene linked to the 850-bp upstream region of the predicted transcription
      start site confirmed that this region drives the muscle-specific expression of
      the primary transcript of miR-1/miR-133. In many deuterostome lineages, including
      that of Ciona, the miR-1/133 cluster is located in the same intron of the mind
      bomb (mib) gene in reverse orientation. Our results suggest that the origin of
      genomic organization and muscle-specific regulation of miR-1/133 can be traced
      back to the ancestor of chordates. Duplication of this miR cluster might have led
      to the remarkable elaboration in the morphology and function of skeletal muscles
      in the vertebrate lineage.

PMID- 23159540
TI  - Overexpression of AMP-activated protein kinase or protein kinase D prevents lipid
      induced insulin resistance in cardiomyocytes.
AB  - During lipid oversupply, the heart becomes insulin resistant, as exemplified by
      defective insulin-stimulated glucose uptake, and will develop diastolic
      dysfunction. In the healthy heart, not only insulin, but also increased
      contractile activity stimulates glucose uptake. Upon increased contraction both
      AMP-activated protein kinase (AMPK) and protein kinase D (PKD) are activated, and
      mediate the stimulation of glucose uptake into cardiomyocytes. Therefore, each of
      these kinases is a potential therapeutic target in the diabetic heart because
      they may serve to bypass defective insulin-stimulated glucose uptake. To test the
      preventive potential of these kinases against loss of insulin-stimulated glucose
      uptake, AMPK or PKD were adenovirally overexpressed in primary cultures of
      insulin resistant cardiomyocytes for assaying substrate uptake, insulin
      responsiveness and lipid accumulation. To induce insulin resistance and lipid
      loading, rat primary cardiomyocytes were cultured in the presence of high insulin
      (100 nM; HI) or high palmitate (palmitate/BSA: 3/1; HP). HI and HP each reduced
      insulin responsiveness, and increased basal palmitate uptake and lipid storage.
      Overexpression of each of the kinases prevented loss of insulin-stimulated
      glucose uptake. Overexpression of AMPK also prevented loss of insulin signaling
      in HI- and HP-cultured cardiomyocytes, but did not prevent lipid accumulation. In
      contrast, overexpression of PKD prevented lipid accumulation, but not loss of
      insulin signaling in HI- and HP-cultured cardiomyocytes. In conclusion, AMPK and
      PKD prevent loss of insulin-stimulated glucose uptake into cardiomyocytes
      cultured under insulin resistance-inducing conditions through different
      mechanisms. This article is part of a Special Issue entitled "Focus on Cardiac
      Metabolism".

PMID- 23159541
TI  - Recent advances in chitosan-based nanoparticles for oral delivery of
      macromolecules.
AB  - Chitosan (CS), a cationic polysaccharide, is widely regarded as a safe and
      efficient intestinal absorption enhancer of therapeutic macromolecules, owing to
      its inherent mucoadhesive feature and ability to modulate the integrity of
      epithelial tight junctions reversibly. By using CS-based nanoparticles, many
      studies have attempted to protect the loaded macromolecules against acidic
      denaturation and enzymatic degradation, prolong their intestinal residence time,
      and increase their absorption by the intestinal epithelium. Derivatives of CS
      such as quaternized CS, thiolated CS and carboxylated CS have also been examined
      to further enhance its effectiveness in oral absorption of macromolecular drugs.
      This review article describes the synthesis of these CS derivatives and their
      characteristics, as well as their potential transport mechanisms of
      macromolecular therapeutics across the intestinal biological membrane. Recent
      advances in using CS and its derivatives as carriers for oral delivery of
      hydrophilic macromolecules and their effects on drug transport are also reviewed.

PMID- 23159542
TI  - Participation of estrogen receptors in the antidepressant-like effect of prolame
      on the forced swimming test.
AB  - Estrogen therapy may produce antidepressant-like actions, but the side effects,
      such as thromboembolic events, may restrict its use among women. The 17beta
      aminoestrogens (AEs) [prolame [17beta-(3-hidroxy-1-propylamino)-1,3,5(10)
      estratrien-3-ol)], butolame [17beta-(3-hidroxy-1-butylamino)-1,3,5(10)-estratrien
      3-ol)], and pentolame [17beta-(5-hidroxy-1-pentylamino)-1,3,5(10)-estratrien-3
      ol)] induce estrogenic and anticoagulant actions, effects that could prove
      advantageous in an estrogen therapy; however, their antidepressant-like effects
      have not been described. The objective of this study was to determine the effect
      of these 17beta-AEs (prolame, butolame and pentolame) in the forced swimming test
      (FST), an animal model sensitive to antidepressant drugs, and to establish the
      role of estrogen receptors in such actions. Ovariectomized female rats treated
      with prolame (10-200 MUg/rat) showed a reduction in immobility and an increase in
      active behaviors in the FST, while this effect was not produced by butolame and
      pentolame (10-200 MUg/rat). The antidepressant-like effect of prolame was similar
      to that of 17beta-estradiol (E2, 5-20 MUg/rat), sharing with it a biphasic
      profile but at higher doses. Antidepressant-like actions of prolame and E2 were
      not associated with changes in locomotor activity. With respect to a control
      group tamoxifen (15 mg/kg) by itself produced no changes in all behavioral
      evaluations, but canceled the antidepressant-like effect of prolame and E2. It is
      concluded that estrogen receptors participate in antidepressant-like effect of
      both estrogens in the FST. Antidepressant-like activity of different AEs is
      discussed considering their differences in chemical structure and the schedule
      used. Our results show additional central actions of prolame besides its pro
      sexual, anti-coagulant, estrogenic and anxiolytic activity.

PMID- 23159543
TI  - Peripherally injected linalool and bergamot essential oil attenuate mechanical
      allodynia via inhibiting spinal ERK phosphorylation.
AB  - Bergamot essential oil (BEO) is one of the most common essential oil containing
      linalool and linalyl acetate as major volatile components. This study
      investigated the effect of intraplantar (i.pl.) bergamot essential oil (BEO) or
      linalool on neuropathic hypersensitivity induced by partial sciatic nerve
      ligation (PSNL) in mice. The i.pl. injection of BEO or linalool into the
      ipsilateral hindpaw to PSNL reduced PSNL-induced mechanical allodynia in a dose
      dependent manner. Peripheral (i.pl.) injection of BEO or linalool into the
      contralateral hindpaw did not yield anti-allodynic effects, suggesting a local
      anti-mechanical allodynic effect of BEO or linalool in PSNL mice. Anti-mechanical
      hypersensitivity of morphine was enhanced by the combined injection of BEO or
      linalool at an ineffective dose when injected alone. We also examined the
      possible involvement of spinal extracellular signal-regulated protein kinase
      (ERK) in BEO or linalool-induced anti-mechanical allodynia. In western blotting
      analysis, i.pl. injection of BEO or linalool resulted in a significant blockade
      of spinal ERK activation induced by PSNL. These results suggest that i.pl.
      injection of BEO or linalool may reduce PSNL-induced mechanical allodynia
      followed by decreasing spinal ERK activation.

PMID- 23159544
TI  - Morphine prevents the development of stress-enhanced fear learning.
AB  - The current study investigates the pharmacotherapeutic use of morphine as a
      preventative treatment for stress-enhanced fear learning, an animal model that
      closely mimics symptoms of post-traumatic stress disorder (PTSD). PTSD is a
      chronic and debilitating anxiety disorder characterized by exaggerated fear
      and/or anxiety that may develop as a result of exposure to a traumatic event. In
      this model, rats are exposed to a severe stressor (15 foot shocks) in one
      environment (Context A) and then subsequently exposed to a milder form of the
      same stressor (single foot shock) in a different environment (Context B). Animals
      that did not receive prior shock treatment exhibit fear responsiveness to Context
      B in line with the severity of the single shock given in this context. Animals
      that had received prior shock treatment in Context A exhibit an exaggerated
      learned fear response to Context B. Furthermore, animals receiving a single dose
      of morphine immediately following the severe stressor in Context A continue to
      show an enhanced fear response in Context B. However, animals receiving repeated
      morphine administration (three injections) after exposure to the severe stressor
      in Context A or a single dose of morphine at 48 h after the severe stressor no
      longer exhibit an enhancement in fear learning to Context B. These results are
      consistent with clinical studies suggesting that morphine treatment following a
      severe stressor may be useful in preventing or reducing the severity of PTSD in
      at-risk populations.

PMID- 23159545
TI  - Reduced protein oxidation in Wistar rats supplemented with marine omega3 PUFAs.
AB  - The potential effects of various dietary eicosapentaenoic acid (EPA; 20:5) and
      docosahexaenoic acid (DHA; 22:6) ratios (1:1, 2:1, and 1:2, respectively) on
      protein redox states from plasma, kidney, skeletal muscle, and liver were
      investigated in Wistar rats. Dietary fish oil groups were compared with animals
      fed soybean and linseed oils, vegetable oils enriched in omega6 linoleic acid
      (LA; 18:2) and omega3 alpha-linolenic acid (ALA; 18:3), respectively. Fish oil
      treatments were effective at reducing the level of total fatty acids in plasma
      and enriching the plasmatic free fatty acid fraction and erythrocyte membranes in
      EPA and DHA. A proteomic approach consisting of fluorescein 5-thiosemicarbazide
      (FTSC) labeling of protein carbonyls, FTSC intensity visualization on 1-DE or 2
      DE gels, and protein identification by MS/MS was used for the protein oxidation
      assessment. Albumin was found to be the most carbonylated protein in plasma for
      all dietary groups, and its oxidation level was significantly modulated by
      dietary interventions. Supplementation with an equal EPA:DHA ratio (1:1) showed
      the lowest oxidation score for plasma albumin, followed in increasing order of
      carbonylation by 1:2 <2:1 ~ linseed < soybean. Oxidation patterns of myofibrillar
      skeletal muscle proteins and cytosolic proteins from kidney and liver also
      indicated a protective effect on proteins for the fish oil treatments, the 1:1
      ratio exhibiting the lowest protein oxidation scores. The effect of fish oil
      treatments at reducing carbonylation on specific proteins from plasma (albumin),
      skeletal muscle (actin), and liver (albumin, argininosuccinate synthetase, 3
      alpha-hydroxysteroid dehydrogenase) was remarkable. This investigation highlights
      the efficiency of dietary fish oil at reducing in vivo oxidative damage of
      proteins compared to oils enriched in the 18-carbon polyunsaturated fatty acids
      omega3 ALA and omega6 LA, and such antioxidant activity may differ among
      different fish oil sources because of variations in EPA/DHA content.

PMID- 23159546
TI  - Antioxidant functions for the hemoglobin beta93 cysteine residue in erythrocytes
      and in the vascular compartment in vivo.
AB  - The beta93 cysteine (beta93Cys) residue of hemoglobin is conserved in vertebrates
      but its function in the red blood cell (RBC) remains unclear. Because this
      residue is present at concentrations more than 2 orders of magnitude higher than
      enzymatic components of the RBC antioxidant network, a role in the scavenging of
      reactive species was hypothesized. Initial studies utilizing mice that express
      human hemoglobin with either Cys (B93C) or Ala (B93A) at the beta93 position
      demonstrated that loss of the beta93Cys did not affect activities nor expression
      of established components of the RBC antioxidant network (catalase, superoxide
      dismutase, peroxiredoxin-2, glutathione peroxidase, GSH:GSSG ratios).
      Interestingly, exogenous addition to RBCs of reactive species that are involved
      in vascular inflammation demonstrated a role for the beta93Cys in hydrogen
      peroxide and chloramine consumption. To simulate oxidative stress and
      inflammation in vivo, mice were challenged with lipopolysaccharide (LPS).
      Notably, LPS induced a greater degree of hypotension and lung injury in B93A
      versus B93C mice, which was associated with greater formation of RBC reactive
      species and accumulation of DMPO-reactive epitopes in the lung. These data
      suggest that the beta93Cys is an important effector within the RBC antioxidant
      network, contributing to the modulation of tissue injury during vascular
      inflammation.

PMID- 23159547
TI  - Predictors of early dyspnoea relief in acute heart failure and the association
      with 30-day outcomes: findings from ASCEND-HF.
AB  - AIMS: To examine the characteristics associated with early dyspnoea relief during
      acute heart failure (HF) hospitalization, and its association with 30-day
      outcomes. METHODS AND RESULTS: ASCEND-HF was a randomized trial of nesiritide vs.
      placebo in 7141 patients hospitalized with acute HF in which dyspnoea relief at 6
      h was measured on a 7-point Likert scale. Patients were classified as having
      early dyspnoea relief if they experienced moderate or marked dyspnoea improvement
      at 6 h. We analysed the clinical characteristics, geographical variation, and
      outcomes (mortality, mortality/HF hospitalization, and mortality/hospitalization
      at 30 days) associated with early dyspnoea relief. Early dyspnoea relief occurred
      in 2984 patients (43%). In multivariable analyses, predictors of dyspnoea relief
      included older age and oedema on chest radiograph; higher systolic blood
      pressure, respiratory rate, and natriuretic peptide level; and lower serum blood
      urea nitrogen (BUN), sodium, and haemoglobin (model mean C index = 0.590).
      Dyspnoea relief varied markedly across countries, with patients enrolled from
      Central Europe having the lowest risk-adjusted likelihood of improvement. Early
      dyspnoea relief was associated with lower risk-adjusted 30-day mortality/HF
      hospitalization [hazard ratio (HR) 0.81; 95% confidence interval (CI) 0.68-0.96]
      and mortality/hospitalization (HR 0.85; 95% CI 0.74-0.99), but similar mortality.
      CONCLUSION: Clinical characteristics such as respiratory rate, pulmonary oedema,
      renal function, and natriuretic peptide levels are associated with early dyspnoea
      relief, and moderate or marked improvement in dyspnoea was associated with a
      lower risk for 30-day outcomes.

PMID- 23159548
TI  - [Diagnosis of IgG4-related systemic disease in a patient with an ocular tumor
      associated with lung nodules].
AB  - The IgG4-related systemic disease is a recently described entity of fibro
      inflammatory systemic damage. Although initially described in some forms of
      pancreatitis, the disease can affect all organs. The common histological features
      include a lymphoplasmacytic infiltration (especially to IgG4), fibrosis and
      phlebitis. Elevated serum level of IgG4 is also often present. This rare but
      certainly underdiagnosed disease must be kept in mind of all clinician faced to a
      non-specific inflammatory lesion. We report a case of ocular inflammation and
      lung tumors in a patient of 84 years for which the diagnosis was made through
      immunolabelling with IgG4 in lesions biopsied.

PMID- 23159549
TI  - Matrix metalloproteinase-12 contributes to neuroinflammation in the aged brain.
AB  - During aging the brain displays an increased proinflammatory status, which is
      associated with the pathogenesis of aging-related diseases such as Alzheimer's
      and Parkinson diseases. Matrix metalloproteinases (MMPs) facilitate the migration
      of inflammatory cells in tissues and modulate their inflammatory activity. In
      this study, we screened expression of MMPs in 3-, 10-, and 18-month-old mice and
      observed that cerebral MMP-12 expression was strongly upregulated during aging.
      We compared the neuroinflammation of 3-, 10-, and 18-month-old MMP-12-deficient
      versus wild type mice by counting microglia and measuring inflammatory gene
      transcripts in the brain and observed that MMP-12 deficiency reduced
      neuroinflammation during aging. In order to identify potential mechanisms, we
      analyzed the inflammatory activity of microglia directly isolated from adult
      mouse brains or cultured from newborn mice. We observed that MMP-12 deficiency
      increased the inflammatory activity of adult brain-derived microglia, but did not
      affect cultured microglia. We found greater numbers of CD11b/CD45(high) cells in
      the parenchyma of MMP-12 wild type than in the parenchyma of MMP-12-deficient
      mouse brains. Thus, our study suggested that the upregulated cerebral MMP-12
      during aging enhances aging-associated neuroinflammation by facilitating
      recruitment of bone marrow-derived microglia into the brain.

PMID- 23159551
TI  - Sprint Fidelis lead fractures in patients with cardiac resynchronization therapy
      devices: insight from the Resynchronization/Defibrillation for Ambulatory Heart
      Failure (RAFT) study.
AB  - BACKGROUND: Using data from the Resynchronization/Defibrillation for Ambulatory
      Heart Failure (RAFT) study, we examined whether Fidelis lead failure was more
      common in patients with implantable cardioverter-defibrillators (ICDs) and
      cardiac resynchronization therapy (ICD-CRT) than in patients with an ICD only.
      METHODS AND RESULTS: All cases of patients who had a right ventricular
      defibrillation lead revision in the RAFT study were adjudicated for the presence
      of lead fracture. Criteria for fracture were at least 2 of the following: (1)
      Impedance rise (>50% or >500 Omega in 1 week), (2) short interval count >10 times
      per day or 300 times per month, or (3) inappropriate shock caused by noise,
      verified by stored electrogram. A total of 1798 patients were enrolled into the
      RAFT study, with a mean follow-up of 40+/-20 months. There were 818 patients
      (45.5%) who received a Fidelis lead at the original implantation, 405 with an ICD
      only and 413 with an ICD-CRT. There were 47 confirmed defibrillation lead
      fractures; 45 were Fidelis leads (5.5% of Fidelis leads). The overall rate of
      fracture in the ICD group was 3.2% compared with 7.8% in the ICD-CRT group
      (P=0.006; hazard ratio, 2.42; 95% confidence interval, 1.27-4.61). Significant
      correlates of lead fracture in this population were undergoing an ICD-CRT
      implantation and having >=2 leads. CONCLUSIONS: In this analysis of the RAFT
      study, patients with an ICD-CRT were found to have a significantly higher
      fracture rate than patients with an ICD. This finding needs to be considered when
      these patients are assessed for possible lead revision at the time of an elective
      generator replacement.

PMID- 23159550
TI  - APOE and neuroenergetics: an emerging paradigm in Alzheimer's disease.
AB  - APOE is the major known genetic risk factor for late-onset Alzheimer's disease.
      Though relationships between APOE-encoded apolipoprotein E and beta-amyloid are
      increasingly well described, mounting evidence supports wide-ranging effects of
      APOE on the brain. Specifically, APOE appears to affect brain network activity
      and closely related neuroenergetic functions that might be involved in
      vulnerability to neurodegenerative pathophysiology. These effects highlight the
      salience of further investigation into the diverse influences of APOE. Therefore,
      this article reviews the interplay between APOE and neuroenergetics and proposes
      areas for further investigation. This research might lead to the identification
      of novel therapeutic targets for the treatment and/or prevention of Alzheimer's
      disease.

PMID- 23159552
TI  - Stroke after carotid stenting and endarterectomy in the Carotid Revascularization
      Endarterectomy versus Stenting Trial (CREST).
AB  - BACKGROUND: Stroke occurs more commonly after carotid artery stenting than after
      carotid endarterectomy. Details regarding stroke type, severity, and
      characteristics have not been reported previously. We describe the strokes that
      have occurred in the Carotid Revascularization Endarterectomy versus Stenting
      Trial (CREST). METHODS AND RESULTS: CREST is a randomized, open-allocation,
      controlled trial with blinded end-point adjudication. Stroke was a component of
      the primary composite outcome. Patients who received their assigned treatment
      within 30 days of randomization were included. Stroke was adjudicated by a panel
      of board-certified vascular neurologists with secondary central review of
      clinically obtained brain images. Stroke type, laterality, timing, and outcome
      were reported. A periprocedural stroke occurred among 81 of the 2502 patients
      randomized and among 69 of the 2272 in the present analysis. Strokes were
      predominantly minor (81%, n=56), ischemic (90%, n=62), in the anterior
      circulation (94%, n=65), and ipsilateral to the treated artery (88%, n=61). There
      were 7 hemorrhages, which occurred 3 to 21 days after the procedure, and 5 were
      fatal. Major stroke occurred in 13 (0.6%) of the 2272 patients. The estimated 4
      year mortality after stroke was 21.1% compared with 11.6% for those without
      stroke. The adjusted risk of death at 4 years was higher after periprocedural
      stroke (hazard ratio, 2.78; 95% confidence interval, 1.63-4.76). CONCLUSIONS:
      Stroke, particularly severe stroke, was uncommon after carotid intervention in
      CREST, but stroke was associated with significant morbidity and was independently
      associated with a nearly 3-fold increased future mortality. The delayed timing of
      major and hemorrhagic stroke after revascularization suggests that these strokes
      may be preventable.

PMID- 23159553
TI  - Measurement and interpretation of the ankle-brachial index: a scientific
      statement from the American Heart Association.

PMID- 23159555
TI  - Matrix-assisted laser desorption ionization time-of-flight mass spectrometry for
      bacterial strain characterization.
AB  - Matrix-assisted laser desorption ionization time-of-flight mass spectrometry
      (MALDI-TOF MS) has emerged as a new technique for rapid and effective bacterial
      species identification in clinical microbiology laboratories. Conventional
      bacterial identification is based essentially on biochemical tests and requires
      lengthy incubation procedures. By contrast, MALDI-TOF MS can identify bacterial
      species in a few minutes, directly from a freshly grown colony. Various
      approaches have been developed for bacterial identification and the efficacy of
      this method has been demonstrated in several studies. This technique should also
      be suitable for the classification of organisms to subspecies level and for the
      phenotypic detection of certain antibiotic resistance mechanisms, such as beta
      lactamases production.

PMID- 23159554
TI  - Associations of total and high-molecular-weight adiponectin with all-cause and
      cardiovascular mortality in older persons: the Cardiovascular Health Study.
AB  - BACKGROUND: Adiponectin shows opposite associations with adverse outcomes in
      healthy middle-aged populations (lower risk) and cohorts with prevalent
      cardiovascular disease, heart failure, or advanced age (higher risk). METHODS AND
      RESULTS: In a population-based study of older adults, we examined the
      relationships of total and high-molecular-weight adiponectin with mortality among
      subgroups defined by baseline cardiovascular status: No cardiovascular disease,
      heart failure, or atrial fibrillation (group 1); cardiovascular disease but no
      heart failure/atrial fibrillation (group 2); and heart failure/atrial
      fibrillation (group 3). We found significant differences in the associations with
      all-cause mortality across the groups. The association in group 1 was U-shaped;
      increasing levels of total adiponectin up to 12.4 mg/L were associated with lower
      mortality after adjustment for confounders (hazard ratio=0.81 per 1 SD [95%
      confidence interval, 0.65-0.95]), but above this cut point, higher levels
      conferred greater risk (hazard ratio=1.19 [95% confidence interval, 1.12-1.27]).
      Further adjustment for diabetes mellitus or insulin resistance, protection
      against which has been proposed to mediate the beneficial relationships of
      adiponectin with outcome, attenuated the association in the lower range. There
      was no significant association in group 2, but in group 3, total adiponectin
      showed a direct adjusted association. Additional adjustment for putative
      metabolic/inflammatory intermediates suggested a direct association for group 2,
      and magnified the one for group 3 (hazard ratio=1.31 [1.15-1.50]). Results were
      similar for high-molecular-weight adiponectin and for cardiovascular mortality.
      CONCLUSIONS: Adiponectin exhibits distinct associations with mortality in elders,
      which shift from U-shaped to flat to direct with greater baseline cardiovascular
      dysfunction but become more consistently adverse after accounting for
      metabolic/inflammatory factors presumed to be favorably regulated by the
      adipokine. These findings advance understanding of the adiponectin paradox as it
      relates to older adults.

PMID- 23159556
TI  - Rapid conformational epitope mapping of anti-gp120 antibodies with a designed
      mutant panel displayed on yeast.
AB  - gp120 is a substrate for protein engineering both for human immunodeficiency
      virus (HIV) immunogen design and as a bait for isolating anti-HIV antibodies from
      patient samples. In this work, we describe the display of a stripped core gp120
      on the yeast cell surface. Validation against a panel of neutralizing antibodies
      confirms that yeast-displayed gp120 presents the CD4 binding site in the correct
      conformation. We map the epitope of the broadly neutralizing anti-gp120 antibody
      VRC01 using both a random mutagenesis library and a defined mutant panel and find
      that the resultant epitope maps are consistent with one another and with the
      crystallographically identified contact residues. Mapping the VRC01-competitive
      antibodies b12 and b13 reveals energetic differences in their epitopes that are
      not obvious from existing crystal structures. These data suggest mutation sets
      that abrogate binding to broadly neutralizing antibodies with greater specificity
      than the canonical mutation D368R, useful in rapidly assessing the nature of a
      vaccine response.

PMID- 23159558
TI  - Biochemical characterization of the Caenorhabditis elegans FBF.CPB-1
      translational regulation complex identifies conserved protein interaction
      hotspots.
AB  - Caenorhabditis elegans CPB-1 (cytoplasmic polyadenylation element binding protein
      homolog-1) and FBF (fem-3 mRNA binding factor) are evolutionary conserved
      regulators of mRNA translation that belong to the CPEB (cytoplasmic
      polyadenylation element binding) and PUF (Pumilio and FBF) protein families,
      respectively. In hermaphrodite worms, CPB-1 and FBF control key steps during
      germline development, including stem cell maintenance and sex determination.
      While CPB-1 and FBF are known to interact, the molecular basis and function of
      the CPB-1?FBF complex are not known. The surface of CPB-1 that interacts with FBF
      was localized using in vivo and in vitro methods to a 10-residue region at the N
      terminus of the protein and these residues are present in the FBF-binding protein
      GLD-3 (germline development defective-3). PUF proteins are characterized by the
      presence of eight alpha-helical repeats (PUF repeats) arranged side by side in an
      elongated structure. Critical residues for CPB-1 binding are found in the
      extended loop that connects PUF repeats 7 and 8. The same FBF residues also
      mediate binding to GLD-3, indicating a conserved binding mode between different
      protein partners. CPB-1 binding was competitive with GLD-3, suggestive of mutual
      exclusivity in vivo. RNA binding measurements demonstrated that CPB-1 alters the
      affinity of FBF for specific RNA sequences, implying a functional model where the
      coregulatory protein CPB-1 modulates FBF target selection.

PMID- 23159557
TI  - (77)Se enrichment of proteins expands the biological NMR toolbox.
AB  - Sulfur, a key contributor to biological reactivity, is not amendable to
      investigations by biological NMR spectroscopy. To utilize selenium as a
      surrogate, we have developed a generally applicable (77)Se isotopic enrichment
      method for heterologous proteins expressed in Escherichia coli. We demonstrate
      (77)Se NMR spectroscopy of multiple selenocysteine and selenomethionine residues
      in the sulfhydryl oxidase augmenter of liver regeneration (ALR). The resonances
      of the active-site residues were assigned by comparing the NMR spectra of ALR
      bound to oxidized and reduced flavin adenine dinucleotide. An additional
      resonance appears only in the presence of the reducing agent and disappears
      readily upon exposure to air and subsequent reoxidation of the flavin. Hence,
      (77)Se NMR spectroscopy can be used to report the local electronic environment of
      reactive and structural sulfur sites, as well as changes taking place in those
      locations during catalysis.

PMID- 23159560
TI  - Membrane active antimicrobial activity and molecular dynamics study of a novel
      cationic antimicrobial peptide polybia-MPI, from the venom of Polybia paulista.
AB  - As the frequent emergence of the resistant bacteria, the development of new
      agents with a new action mode attracts a great deal of interest. It is now widely
      accepted that antimicrobial peptides (AMPs) are promising alternatives to
      conventional antibiotics. In this study, antimicrobial peptide polybia-MPI and
      its analogs were synthesized and their antibacterial activity was studied. Our
      results revealed that polybia-MPI has potent antibacterial activity against both
      Gram-positive and Gram-negative bacteria. Its ability to make PI permeate into
      bacteria and lead to the leakage of calcein from model membrane LUVs, suggests a
      killing mechanism involving membrane perturbation. SEM and TEM microscopy
      experiments verified that the morphology of bacteria was changed greatly under
      the treatment of polybia-MPI. Compared with the conventional chemotherapy,
      polybia-MPI targets the cell membrane rather than entering into the cell to exert
      its antibacterial activity. Furthermore, molecular dynamics (MD) simulations were
      employed to investigate the mechanism of membrane perturbation. The results
      indicated that the alpha-helical conformation in the membrane is required for the
      exhibition of antibacterial activity and the membrane disturbance by polybia-MPI
      is a cooperative process. In conclusion, with the increasing resistance to
      conventional antibiotics, there is no doubt that polybia-MPI could offer a new
      strategy to defend the resistant bacteria.

PMID- 23159561
TI  - Early alterations in plasma ghrelin levels in offspring of calorie-restricted
      rats during gestation may be linked to lower sympathetic drive to the stomach.
AB  - Serum ghrelin concentration is generally reduced in obesity. We aimed to assess
      whether this alteration is present in rats predisposed to obesity because of
      moderate undernutrition during gestation, and to explore whether this could be
      related with alterations in stomach sympathetic innervation, which is involved in
      gastric ghrelin secretion. Offspring of control and 20% gestational calorie
      restricted dams (CR) exposed to normal-fat-diet from weaning onward were studied.
      Circulating ghrelin levels were measured at 25 days and 4 months of age.
      Morphometry, number of ghrelin-positive (ghrelin(+)) cells, ghrelin mRNA and
      protein levels, and tyrosine hydroxylase (TH) protein levels in stomach were
      determined at 25 days. Adult CR male animals, but not females, exhibited greater
      body-weight (BW) than their controls, but both males and females showed lower
      circulating ghrelin levels. This alteration in ghrelin levels was already present
      at 25 days, prior to any difference in BW. At this juvenile age, no differences
      in gastric morphometry, number of ghrelin(+) cells or ghrelin mRNA/protein levels
      were found between control and CR animals, however, CR animals showed lower TH
      stomach content. These results suggest that circulating ghrelin concentration is
      early altered in rats prenatally programmed to develop obesity. This does not
      seem to be associated with lower ghrelin production capacity but with specific
      alterations in sympathetic drive to the stomach.

PMID- 23159559
TI  - A protein.protein interaction platform involved in recruitment of GLD-3 to the
      FBF.fem-3 mRNA complex.
AB  - The Pumilio and FBF (PUF) family of RNA-binding proteins interacts with protein
      partners to post-transcriptionally regulate mRNAs in eukaryotes. The interaction
      between PUF family member fem-3 binding factor (FBF) and germline development
      defective-3 (GLD-3) protein promotes spermatogenesis in Caenorhabditis elegans by
      increasing expression of the fem-3 mRNA. Defined here in these studies is the
      molecular basis for this critical interaction. A 10-amino-acid region within GLD
      3 is required for FBF binding, while a 7-amino-acid loop in FBF between PUF
      repeats 7 and 8 is necessary for GLD-3 binding. These short sequences are
      conserved, as other FBF-binding proteins bear sequences similar to those in GLD-3
      and other C. elegans PUF proteins contain sequences similar to those in FBF. The
      FBF-binding region of GLD-3 forms a ternary complex with FBF on the point
      mutation element (PME) in the fem-3 3' untranslated region, and formation of this
      GLD-3?FBF complex does not impact the RNA-binding activity of FBF. These data
      raise the possibility of alternative models involving the formation of a GLD
      3?FBF?RNA complex in the regulation of germline mRNAs.

PMID- 23159562
TI  - Esculentin-2CHa: a host-defense peptide with differential cytotoxicity against
      bacteria, erythrocytes and tumor cells.
AB  - The host-defense peptide, esculentin-2CHa (GFSSIFRGVA(10)KFASKGLGK
      D(20)LAKLGVDLVA(30) CKISKQC) shows potent (MIC<=6 MUM) growth inhibitory activity
      against clinical isolates of multidrug-resistant strains of Staphylococcus
      aureus, Acinetobacter baumannii, and Stenotrophomonas maltophilia and
      differential cytotoxic activity against human erythrocytes (LC(50)=150 MUM) and
      human non-small cell lung adenocarcinoma A549 cells (LC(50)=10 MUM). Esculentin
      2CHa significantly (P<0.01) stimulates the release of the anti-inflammatory
      cytokine IL-10 by mouse lymphoid cells and elevates its production after
      stimulation with concanavalin A and significantly (P<0.05) stimulates TNF-alpha
      production by peritoneal macrophages. Effects on IL-6 and IL-1beta production
      were not significant. Removal of the hydrophobic N-terminal hexapeptide (GFSSIF)
      from esculentin-2CHa results in abolition of growth inhibitory activity against
      S. aureus and cytotoxic activity against erythrocytes and A549 cells as well as a
      marked (>=16-fold) reduction in potency against A. baumannii and S. maltophilia.
      The primary structure of esculentin-2 has been poorly conserved between frog
      species but evolutionary pressure has acted to maintain the hydrophobic character
      of this N-terminal hexapeptide sequence. Removal of the cyclic C-terminal domain
      (CKISKQC) and replacement of the Cys(31) and Cys(37) residues by serine resulted
      in appreciable decreases in cytotoxicity against all microorganisms and against
      mammalian cells. The more cationic [D20K, D27K] analog showed a modest increase
      in potency against all microorganisms (up to 4-fold) but a marked increase in
      cytotoxicity against erythrocytes (LC(50)=11 MUM) and A549 cells (LC(50)=3 MUM).

PMID- 23159563
TI  - Engineering osteochondral constructs through spatial regulation of endochondral
      ossification.
AB  - Chondrogenically primed bone marrow-derived mesenchymal stem cells (MSCs) have
      been shown to become hypertrophic and undergo endochondral ossification when
      implanted in vivo. Modulating this endochondral phenotype may be an attractive
      approach to engineering the osseous phase of an osteochondral implant. The
      objective of this study was to engineer an osteochondral tissue by promoting
      endochondral ossification in one layer of a bilayered construct and stable
      cartilage in the other. The top half of bilayered agarose hydrogels were seeded
      with culture expanded chondrocytes (termed the chondral layer) and the bottom
      half of the bilayered agarose hydrogels with MSCs (termed the osseous layer).
      Constructs were cultured in chondrogenic medium for 21days and thereafter were
      either maintained in chondrogenic medium, transferred to hypertrophic medium, or
      implanted subcutaneously into nude mice. This structured chondrogenic bilayered
      co-culture was found to enhance chondrogenesis in the chondral layer, appearing
      to help re-establish the chondrogenic phenotype that is lost in chondrocytes
      during monolayer expansion. Furthermore, the bilayered co-culture appeared to
      suppress hypertrophy and mineralization in the osseous layer. The addition of
      hypertrophic factors to the media was found to induce mineralization of the
      osseous layer in vitro. A similar result was observed in vivo where endochondral
      ossification was restricted to the osseous layer of the construct, leading to the
      development of an osteochondral tissue. This novel approach represents a
      potential new treatment strategy for the repair of osteochondral defects.

PMID- 23159564
TI  - Effect of cold rolling on the magnetic susceptibility of Zr-14Nb alloy.
AB  - The magnetic susceptibility of cold-rolled Zr-14Nb was evaluated to apply a new
      metallic medical device used for magnetic resonance imaging (MRI). The magnetic
      susceptibility of cold-rolled Zr-14Nb decreased up to the reduction ratio of 30%,
      then gradually decreased up to the ratio of 90%. Transmission electron
      microscopic observation revealed the strain-induced formation of omega phase
      after cold rolling at the reduction ratio of 5%, indicating that the initial
      decrease in magnetic susceptibility was caused by the formation of the omega
      phase. The omega phase was saturated at the reduction ratio of 30%. The formation
      of the omega phase could be explained on the basis of the increase in the Young's
      modulus and Vickers hardness of cold-rolled Zr-14Nb. The effect of texture
      formation on these properties was not obvious in the cold-rolled Zr-14Nb. Because
      of the strain-induced formation of the omega phase, the magnetic susceptibility
      of Zr-14Nb can be reduced by cold rolling to as low as that of as-cast Zr-9Nb,
      which is one-third that of Ti and Ti alloys. Therefore, cold-workable Zr-14Nb
      with low magnetic susceptibility could be a promising alloy for medical devices
      under MRI.

PMID- 23159565
TI  - Incorporation of bioactive glass in calcium phosphate cement: An evaluation.
AB  - Bioactive glasses (BGs) are known for their unique ability to bond to living
      bone. Consequently, the incorporation of BGs into calcium phosphate cement (CPC)
      was hypothesized to be a feasible approach to improve the biological performance
      of CPC. Previously, it has been demonstrated that BGs can successfully be
      introduced into CPC, with or without poly(d,l-lactic-co-glycolic) acid (PLGA)
      microparticles. Although an in vitro physicochemical study on the introduction of
      BG into CPC was encouraging, the biocompatibility and in vivo bone response to
      these formulations are still unknown. Therefore, the present study aimed to
      evaluate the in vivo performance of BG supplemented CPC, either pure or
      supplemented with PLGA microparticles, via both ectopic and orthotopic
      implantation models in rats. Pre-set scaffolds in four different formulations (1:
      CPC; 2: CPC/BG; 3: CPC/PLGA; and 4: CPC/PLGA/BG) were implanted subcutaneously
      and into femoral condyle defects of rats for 2 and 6 weeks. Upon ectopic
      implantation, incorporation of BG into CPC improved the soft tissue response by
      improving capsule and interface quality. Additionally, the incorporation of BG
      into CPC and CPC/PLGA showed 1.8- and 4.7-fold higher degradation and 2.2- and
      1.3-fold higher bone formation in a femoral condyle defect in rats compared to
      pure CPC and CPC/PLGA, respectively. Consequently, these results highlight the
      potential of BG to be used as an additive to CPC to improve the biological
      performance for bone regeneration applications. Nevertheless, further
      confirmation is necessary regarding long-term in vivo studies, which also have to
      be performed under compromised wound-healing conditions.

PMID- 23159566
TI  - Biological response on a titanium implant-grade surface functionalized with
      modular peptides.
AB  - Titanium (Ti) and its alloys are among the most successful implantable materials
      for dental and orthopedic applications. The combination of excellent mechanical
      and corrosion resistance properties makes them highly desirable as endosseous
      implants that can withstand a demanding biomechanical environment. Yet, the
      success of the implant depends on its osteointegration, which is modulated by the
      biological reactions occurring at the interface of the implant. A recent
      development for improving biological responses on the Ti-implant surface has been
      the realization that bifunctional peptides can impart material binding
      specificity not only because of their molecular recognition of the inorganic
      material surface, but also through their self-assembly and ease of biological
      conjugation properties. To assess peptide-based functionalization on bioactivity,
      the present authors generated a set of peptides for implant-grade Ti, using cell
      surface display methods. Out of 60 unique peptides selected by this method, two
      of the strongest titanium binding peptides, TiBP1 and TiBP2, were further
      characterized for molecular structure and adsorption properties. These two
      peptides demonstrated unique, but similar molecular conformations different from
      that of a weak binder peptide, TiBP60. Adsorption measurements on a Ti surface
      revealed that their disassociation constants were 15-fold less than TiBP60. Their
      flexible and modular use in biological surface functionalization were
      demonstrated by conjugating them with an integrin recognizing peptide motif,
      RGDS. The functionalization of the Ti surface by the selected peptides
      significantly enhanced the bioactivity of osteoblast and fibroblast cells on
      implant-grade materials.

PMID- 23159567
TI  - Application of galactose-modified liposomes as a potent antigen presenting cell
      targeted carrier for intranasal immunization.
AB  - The mucosal immune system produces secretory IgA (sIgA) as the first line of
      defense against invasion by foreign pathogens. Our aim was to develop a galactose
      modified liposome as a targeted carrier which can be specifically recognized by
      macrophage, one of the most important antigen presenting cells. First, galactose
      was covalently conjugated with 1,2-didodecanoyl-sn-glycero-3-phosphoethanolamine
      (DLPE) to give a targeted ligand, a galactosyl lipid. The galactosyl lipid was
      then incorporated into a liposomal bilayer to form a galactosylated liposome
      carrier. Further, the ovalbumin (OVA) was encapsulated into the galactosylated
      liposome carriers and mice were intranasally immunized. Confocal laser scanning
      microscopy and flow cytometry analysis showed that the targeted galactosylated
      liposome carrier had a higher uptake rate than unmodified liposomes. The targeted
      galactosylated liposome induced higher levels of tumor necrosis factor-alpha and
      interleukin-6 production than unmodified liposomes (P<0.05). Furthermore, 6-week
      old BALB/c female mice immunized with the OVA-encapsulated targeted
      galactosylated liposome had significantly higher OVA-specific s-IgA levels in the
      nasal and lung wash fluid (P<0.05). In addition, the targeted galactosylated
      liposome simultaneously augmented the serum IgG antibody response. In summary,
      the OVA-encapsulated targeted galactosylated liposome induced significantly
      higher mucosal IgA and systemic IgG antibody titers and is a potential antigen
      delivery carrier for further clinical applications.

PMID- 23159568
TI  - Non-proteinogenic amino acids in the pThr-2 position of a pentamer peptide that
      confer high binding affinity for the polo box domain (PBD) of polo-like kinase 1
      (Plk1).
AB  - We report herein that incorporating long-chain alkylphenyl-containing non
      proteinogenic amino acids in place of His at the pT-2 position of the parent polo
      like kinase 1 (Plk1) polo box domain (PBD)-binding pentapeptide, PLHSpT (1a)
      increases affinity. For certain analogs, approximately two orders-of-magnitude
      improvement in affinity was observed. Although, none of the new analogs was as
      potent as our previously described peptide 1b, in which the pT-2 histidine
      imidazole ring is alkylated at its pi nitrogen (N3), our current finding that the
      isomeric His(N1)-analog (1c) binds with approximately 50-fold less affinity than
      1b, indicates the positional importance of attachment to the His imidazole ring.
      Our demonstration that a range of modified residues at the pT-2 position can
      enhance binding affinity, should facilitate the development of minimally-sized
      Plk1 PBD-binding antagonists.

PMID- 23159569
TI  - Discovery and characterization of a novel 7-aminopyrazolo[1,5-a]pyrimidine analog
      as a potent hepatitis C virus inhibitor.
AB  - We describe a novel 7-aminopyrazolo[1,5-a]pyrimidine (7-APP) derivative as a
      potent hepatitis C virus (HCV) inhibitor. A series of 7-APPs was synthesized and
      evaluated for inhibitory activity against HCV in different cell culture systems.
      The synthesis and preliminary structure-activity relationship study of 7-APP are
      reported.

PMID- 23159570
TI  - Functional connections between self-referential thought and chronic pain: a
      dysfunctional relationship.

PMID- 23159571
TI  - Role of microRNA in chronic visceral nociception.

PMID- 23159572
TI  - Lack of clarity in reports of adverse events: is there any harm?

PMID- 23159573
TI  - The emerging field of pain epigenetics.

PMID- 23159574
TI  - Optimism and pain: a positive move forward.

PMID- 23159575
TI  - Postoperative pain management: number-needed-to-treat approach versus procedure
      specific pain management approach.

PMID- 23159576
TI  - Specific actions of GLP-1 receptor agonists and DPP4 inhibitors for the treatment
      of pancreatic beta-cell impairments in type 2 diabetes.
AB  - Type 2 diabetes occurs when the beta-cells do not secrete enough insulin to
      counter balance insulin resistance. GLP-1 and GIP are insulinotropic peptides
      which are thought to benefit to beta-cell physiology. On one hand sustained
      pharmacological levels of GLP-1 are achieved by subcutaneous administration of
      GLP-1 analogs while transient and lower physiological levels of GLP-1 are
      attained following DPP4 inhibitor (DPP4i) treatment. On the other hand, DPP4i
      increase GLP-1 concentration into the portal vein to recruit the gut-to brain-to
      pancreas axis which is not the case with injected analogs. Hence, these
      differences between GLP-1 analogs and DPP4i indicate that both strategies could
      differentially impact beta-cell behavior. Here, we summarize the effects of GLP-1
      analogs and DPP4i on beta-cell physiology. We discuss the possibility that
      production of signaling molecules, such as cAMP, generated into the beta-cells by
      native GLP-1 or pharmacological GLP-1 analogs may vary and engage different
      downstream signaling networks. Hence, deciphering which signaling networks are
      engaged following GLP-1 analogs or DPP4i administration appears to be critical to
      unveil the contribution of each treatment/strategy to engage beta-cell cellular
      processes.

PMID- 23159577
TI  - Role of PKCalpha-p38 MAPK-Gialpha axis in peroxynitrite-mediated inhibition of
      beta-adrenergic response in pulmonary artery smooth muscle cells.
AB  - In the context of cross-talk between transmembrane signaling pathways, we studied
      the loci within the beta-adrenergic receptor/G protein/adenyl cyclase system at
      which PKC exerts regulatory effects of peroxynitrite (ONOO(-)) on isoproterenol
      stimulated adenyl cyclase activity in pulmonary artery smooth muscle cells.
      Treatment of the cells with ONOO(-) stimulated PKC-alpha activity and that
      subsequently increased p(38)MAPK phosphorylation. Pretreatment with Go6976 (PKC
      alpha inhibitor) and SB203580 (p(38)MAPK inhibitor) eliminated ONOO(-) caused
      inhibition on isoproterenol stimulated adenyl cyclase activity. Pretreatment with
      Go6976, but not SB203580, prevented ONOO(-) induced increase in PKC-alpha
      activity. Studies using genetic inhibitors of PKC-alpha (PKC-alpha siRNA) and
      p(38)MAPK (p(38)MAPK siRNA) also corroborated the findings obtained with their
      pharmacological inhibitors in eliminating the attenuation of ONOO(-) effect on
      isoproterenol stimulated adenyl cyclase activity. This inhibitory effect of ONOO(
      ) was found to be eliminated upon pretreatment of the cells with pertussis toxin
      thereby pointing to a G(i) dependent mechanism. This hypothesis was reinforced by
      G(i)alpha phosphorylation as well as by the observation of the loss of the
      ability of Gpp(NH)p (a measure of G(i) mediated response) to stimulate adenyl
      cyclase activity upon ONOO(-) treatment to the cells. We suggest the existence of
      a pertussis toxin sensitive G protein (G(i))-mediated mechanism in isoproterenol
      stimulated adenyl cyclase activity, which is regulated by PKCalpha-p(38)MAPK axis
      dependent phosphorylation of its alpha-subunit (G(i)alpha) in the pulmonary
      artery smooth muscle cells.

PMID- 23159578
TI  - beta-Arrestin-biased signaling of PTH analogs of the type 1 parathyroid hormone
      receptor.
AB  - Parathyroid hormone (PTH) is an anabolic agent that mediates bone formation
      through activation of the Galpha(s)-, Galpha(q)- and beta-arrestin-coupled
      parathyroid hormone receptor type 1 (PTH1R). Pharmacological evidence based on
      the effect of PTH(7-34), a PTH derivative that is said to preferentially activate
      beta-arrestin signaling through PTH1R, suggests that PTH1R-activated beta
      arrestin signaling mediates anabolic effects on bone. Here, we performed a
      thorough evaluation of PTH(7-34) signaling behaviour using quantitative assays
      for beta-arrestin recruitment, Galpha(s)- and Galpha(q)-signaling. We found that
      PTH(7-34) inhibited PTH-induced cAMP accumulation, but was unable to induce beta
      arrestin recruitment, PTH1R internalization and ERK1/2 phosphorylation in HEK293,
      CHO and U2OS cells. Thus, the beta-arrestin bias of PTH(7-34) is not apparent in
      every cell type examined, suggesting that correlating in vivo effects of PTH(7
      34) to in vitro pharmacology should be done with caution.

PMID- 23159579
TI  - Percutaneous implantation of a ventricular partitioning device for treatment of
      ischemic heart failure: initial experience of a center.
AB  - The Parachute is a novel left ventricular (LV) partitioning device that is
      deployed percutaneously in the left ventricle in patients with anteroapical
      regional wall motion abnormalities, dilated LV and systolic dysfunction after
      anterior myocardial infarction (MI). The implantable device is a partitioning
      membrane that isolates the dysfunctional region of the ventricle and decreases
      chamber volume. Data from the first-in-human clinical trial - the Percutaneous
      Ventricular Restoration in Chronic Heart Failure (PARACHUTE) trial- has shown
      that this new device is associated with significant and sustained LV volume
      reduction and improvement in LV hemodynamics and functional capacity in the 12
      months after implantation, with a relatively low rate of clinical events,
      indicating that it may have a beneficial effect in the treatment of ischemic
      heart failure. We aim to describe our initial experience with implantation of the
      Parachute LV partitioning device and its short-term safety, defined as the
      successful delivery and deployment of the device.

PMID- 23159580
TI  - Adverse events in HEAAL: when to hold and when to fold.

PMID- 23159581
TI  - Plasmacytoid urothelial carcinoma, a chemosensitive cancer with poor prognosis,
      and peritoneal carcinomatosis.
AB  - PURPOSE: Plasmacytoid urothelial carcinoma is a rare variant histology with
      poorly defined clinical behavior. We report clinical outcome information on
      patients with predominant plasmacytoid urothelial carcinoma. MATERIALS AND
      METHODS: We retrospectively analyzed treatments and outcomes in patients with
      predominant plasmacytoid urothelial carcinoma seen at our institution from 1990
      through 2010. The Kaplan-Meier method was used to calculate overall and
      progression-free survival. RESULTS: We identified 31 patients with a median age
      of 63.5 years, of whom 83.3% were male. TNM stage was cT1N0 in 4 patients, cT2N0
      in 7, cT3b-4aN0 in 5 and cT4b, N+ or M+ in 15. Median overall survival was 17.7
      months (stage I-III vs IV 45.8 vs 13.3). Five of the 16 patients with potentially
      surgically resectable plasmacytoid urothelial carcinoma (pT4aN0M0 or less)
      received neoadjuvant chemotherapy, 10 underwent initial surgery and 1 was treated
      only with transurethral resection of bladder tumor. Despite pathological down
      staging in 80% of the patients who received neoadjuvant chemotherapy, relapses
      were common. There was no survival difference between patients treated with
      neoadjuvant chemotherapy or initial surgery, although 7 received adjuvant
      chemotherapy. Surgical up staging with positive margins was also common for
      surgery alone. The most common site of recurrence was in the peritoneum (19 of 23
      patients) with relapses even in those with a pathological complete response at
      surgery. In patients who presented with metastatic disease and were treated with
      chemotherapy median survival was 12.6 months. CONCLUSIONS: Plasmacytoid
      urothelial carcinoma is an aggressive subset with overall poor outcomes. Although
      down staging is seen with neoadjuvant chemotherapy, there are few long-term
      survivors. There is a strong predilection for recurrence along the peritoneal
      lining.

PMID- 23159582
TI  - Urinary functional outcome following radical cystoprostatectomy and ileal
      neobladder reconstruction in male patients.
AB  - PURPOSE: Orthotopic neobladder reconstruction is the preferred method of urinary
      diversion after radical cystoprostatectomy. We evaluated urinary functional
      outcomes in male patients after orthotopic neobladder using a patient
      questionnaire. MATERIALS AND METHODS: Between 2002 and 2009 patients with bladder
      cancer were enrolled in a clinical trial, randomly assigned to undergo T pouch or
      Studer pouch diversion after radical cystoprostatectomy. Male patients were
      mailed a questionnaire 12 or more months after surgery including items on urinary
      function, intermittent catheterization, number/size/wetness of pads and mucus
      leakage. RESULTS: The questionnaire response rate was 68%. Mean followup was 4.5
      years (range 1 to 8). Only 22.3% of patients did not use pads. In the daytime 47%
      of patients used at least 1 pad, 32.2% used small/mini pads and 22.6% used
      diapers. At night 72% used pads, 14.7% used small/mini pads and 38.9% used
      diapers. During the day and night 47% said their pads were dry/barely wet.
      Overall 62.5% of patients reported mucus leakage. Only 9.5% of patients performed
      clean intermittent self-catheterization, of whom 70.6% started clean intermittent
      self-catheterization within the first year after surgery. Increasing age and
      diabetes mellitus were predictors of urinary function (p = 0.005 and 0.03,
      respectively) but did not affect pad use. CONCLUSIONS: Ileal orthotopic
      neobladder offers good functional results but most patients wear at least 1 pad
      and many require diapers at night. Increasing age and diabetes mellitus predict
      worse urinary function but are not associated with pad use. Emptying failure is
      uncommon and occurs early in the postoperative period. Pad size/wetness and mucus
      leakage should be considered when evaluating urinary incontinence.

PMID- 23159583
TI  - Lymph node excision for renal cancer.

PMID- 23159585
TI  - Novel evaluation of nephrolithiasis as a complication of gout: a cross-sectional
      study using helical computerized tomography.
AB  - PURPOSE: We clarified whether the clinical profiles of patients with a history of
      urolithiasis (stone formers) truly reflect those of patients who currently have
      renal stones (stone carriers). MATERIALS AND METHODS: We evaluated 463 patients
      with gout using helical computerized tomography, urolithiasis history and
      relevant clinical parameters. RESULTS: Nephrolithiasis was observed in 157 of the
      463 patients (34%) on helical computerized tomography but only 75 (16%) had a
      urolithiasis history. Of the 157 stone carriers 107 (68%) did not have a
      urolithiasis history. In those 157 patients serum urate and serum creatinine were
      higher than in the 306 nonstone carriers (p = 0.017), and the estimated
      glomerular filtration rate and urinary pH were lower (p = 0.0096 and 0.0249,
      respectively). However, there was no significant difference in laboratory
      findings between the 75 stone formers and 388 nonstone formers. Serum urate and
      creatinine were higher, and the estimated glomerular filtration rate and urine pH
      in bilateral stone carriers were lower than in unilateral stone carriers.
      According to HU density attenuation values on computerized tomography, an
      estimated third of the calculi that complicated 31 recent gout cases was uric
      acid. CONCLUSIONS: The concept of stone formers may lead to underestimating the
      prevalence of urolithiasis. Our analysis of stone carriers showed that a higher
      stone burden is associated with greater renal derangement, as determined by serum
      urate and creatinine, the estimated glomerular filtration rate and urine pH. To
      accurately clarify the correlation of gout and urolithiasis, it is advantageous
      to select stone carriers as subjects of study.

PMID- 23159586
TI  - Brief smoking cessation intervention: a prospective trial in the urology setting.
AB  - PURPOSE: Urologists have an important role in the treatment of tobacco related
      diseases, such as kidney and bladder cancer. Despite this role, urologists
      receive little training in promoting tobacco cessation. We prospectively
      evaluated a brief smoking cessation intervention offered by a urologist at an
      outpatient clinic. MATERIALS AND METHODS: Between 2009 and 2011 adult smokers
      from a single institution urology clinic were enrolled in a prospective, brief
      intervention trial or in usual care as controls. All patients were assessed by
      the validated Fagerstrom test for nicotine dependence and the readiness to quit
      questionnaire. Trial patients received a 5-minute brief smoking cessation
      intervention. The primary outcome was abstinence at 1 year and the secondary
      outcome was the number of attempts to quit. Multivariate logistic regression was
      used to identify factors associated with the quit rate and quit attempts.
      RESULTS: A total of 179 patients were enrolled in the study, including 100 in the
      brief smoking cessation intervention, 41 in the brief smoking cessation
      intervention plus nicotine replacement therapy and 38 usual care controls. Of the
      participants 81.0% were 40 years old or older with a mean +/- SD 11.26 +/- 7.23
      pack-year smoking history. Mean readiness to quit and tobacco dependence scores
      were similar in the 2 arms (p = 0.25 and 0.92, respectively). The 1-year quit
      rate in the brief smoking cessation intervention group was 12.1% vs 2.6% in the
      usual care group (OR 4.44, p = 0.163) Adding nicotine replacement therapy
      increased the quit rate to 19.5% (vs usual care OR 9.91, p = 0.039). Patients who
      received the brief smoking cessation intervention were significantly more likely
      to attempt to quit (OR 2.31, p = 0.038). Increased readiness scores were
      associated with an increased quit rate and increased quit attempts. CONCLUSIONS:
      Urologists can successfully implement a brief smoking cessation intervention
      program. Our study highlights the role of the urologist in providing smoking
      cessation assistance and the significant impact of brief, simple advice about
      quitting smoking on the smoker quit rate.

PMID- 23159584
TI  - Using the epigenetic field defect to detect prostate cancer in biopsy negative
      patients.
AB  - PURPOSE: We determined whether a novel combination of field defect DNA
      methylation markers could predict the presence of prostate cancer using
      histologically normal transrectal ultrasound guided biopsy cores. MATERIALS AND
      METHODS: Methylation was assessed using quantitative Pyrosequencing(r) in a
      training set consisting of 65 nontumor and tumor associated prostate tissues from
      University of Wisconsin. A multiplex model was generated using multivariate
      logistic regression and externally validated in blinded fashion in a set of 47
      nontumor and tumor associated biopsy specimens from University of Washington.
      RESULTS: We observed robust methylation differences in all genes at all CpGs
      assayed (p <0.0001). Regression models incorporating individual genes (EVX1, CAV1
      and FGF1) and a gene combination (EVX1 and FGF1) discriminated nontumor from
      tumor associated tissues in the original training set (AUC 0.796-0.898, p
      <0.001). On external validation uniplex models incorporating EVX1, CAV1 or FGF1
      discriminated tumor from nontumor associated biopsy negative specimens (AUC
      0.702, 0.696 and 0.658, respectively, p <0.05). A multiplex model (EVX1 and FGF1)
      identified patients with prostate cancer (AUC 0.774, p = 0.001) and had a
      negative predictive value of 0.909. Comparison between 2 separate cores in
      patients in this validation set revealed similar methylation defects, indicating
      detection of a widespread field defect. CONCLUSIONS: A widespread epigenetic
      field defect can be used to detect prostate cancer in patients with
      histologically negative biopsies. To our knowledge this assay is unique, in that
      it detects alterations in nontumor cells. With further validation this marker
      combination (EVX1 and FGF1) has the potential to decrease the need for repeat
      prostate biopsies, a procedure associated with cost and complications.

PMID- 23159587
TI  - Variability of semen parameters with time in placebo treated men.
AB  - PURPOSE: We describe the variability of semen parameters with time in normal men
      receiving placebo. We also report the impact of season and geographic region,
      among other variables, on these parameters. MATERIALS AND METHODS: Data from the
      placebo arms of 5 randomized, controlled trials were pooled. All trials set
      minimum standards for semen parameters as an eligibility criterion for entry.
      Semen parameters examined include volume, density, motility, total count, total
      motile count and morphology. Mixed model repeated measure analysis was used for
      statistical analysis. Coefficients of variation for each semen parameter and the
      percent change from baseline were calculated. RESULTS: The mean within-subject
      coefficient of variation for each semen parameter ranged from a low of 10% to a
      high of almost 50%. The contribution of season and region to variability was
      negligible. The reduction in variability with an increasing number of samples per
      time point had decreasing returns beyond 2 samples. CONCLUSIONS: There was
      considerable variation in semen parameters with time in subjects who received
      placebo. Variation could not be attributed to season or region. We observed a
      general negative trend in semen parameters in this population selected for normal
      baseline semen parameters, which was likely due to the placebo response or to
      regression toward the mean.

PMID- 23159588
TI  - Pathogenesis of bladder calculi in the presence of urinary stasis.
AB  - PURPOSE: Although minimal evidence exists, bladder calculi in men with benign
      prostatic hyperplasia are thought to be secondary to bladder outlet obstruction
      induced urinary stasis. We performed a prospective, multi-institutional clinical
      trial to determine whether metabolic differences were present in men with and
      without bladder calculi undergoing surgical intervention for benign prostatic
      hyperplasia induced bladder outlet obstruction. MATERIALS AND METHODS: Men who
      elected surgery for bladder outlet obstruction secondary to benign prostatic
      hyperplasia with and without bladder calculi were assessed prospectively and
      compared. Men without bladder calculi retained more than 150 ml urine post-void
      residual urine. Medical history, serum electrolytes and 24-hour urinary metabolic
      studies were compared. RESULTS: Of the men 27 had bladder calculi and 30 did not.
      Bladder calculi were associated with previous renal stone disease in 36.7% of
      patients (11 of 30) vs 4% (2 of 27) and gout was associated in 13.3% (4 of 30) vs
      0% (0 of 27) (p <0.01 and 0.05, respectively). There was no observed difference
      in the history of other medical conditions or in serum electrolytes. Bladder
      calculi were associated with lower 24-hour urinary pH (median 5.9 vs 6.4, p =
      0.02), lower 24-hour urinary magnesium (median 106 vs 167 mmol, p = 0.01) and
      increased 24-hour urinary uric acid supersaturation (median 2.2 vs 0.6, p <0.01).
      CONCLUSIONS: In this comparative prospective analysis patients with bladder
      outlet obstruction and benign prostatic hyperplasia with bladder calculi were
      more likely to have a renal stone disease history, low urinary pH, low urinary
      magnesium and increased urinary uric acid supersaturation. These findings suggest
      that, like the pathogenesis of nephrolithiasis, the pathogenesis of bladder
      calculi is likely complex with multiple contributing lithogenic factors,
      including metabolic abnormalities and not just urinary stasis.

PMID- 23159589
TI  - Cost-effectiveness of anti-retropulsion devices for ureteroscopic lithotripsy.
AB  - PURPOSE: We evaluated the cost-effectiveness of anti-retropulsion devices used
      during ureteroscopic lithotripsy. MATERIALS AND METHODS: A decision analysis
      model was constructed to compare the cost-effectiveness of ureteroscopic
      lithotripsy with vs without an anti-retropulsion device. The risk of stone
      retropulsion was determined from published data in the English language
      literature. Expected value calculations were used to determine whether the
      additional cost of a device would be cost-effective to prevent secondary
      procedures used to treat retropulsed stones. Device cost was determined using the
      average cost of all commercially available devices. RESULTS: It became cost
      effective to use an anti-retropulsion device at or above a 6.3% retropulsion
      rate. The weighted probability of retropulsion with vs without an anti
      retropulsion device was 98.1% vs 83.7%. The estimated costs of secondary
      procedures needed to treat retropulsed stones were $5,290 for shock wave
      lithotripsy and $6,390 for ureteroscopy. Average device cost was $278. Thus, the
      average additional cost of ureteroscopic lithotripsy with vs without an anti
      migration device would be $384 vs $952. CONCLUSIONS: It is cost-effective to use
      an anti-retropulsion device at a retropulsion rate of greater than 6.3%.

PMID- 23159590
TI  - Allele-specific, non-extendable primer blocker PCR (AS-NEPB-PCR) for DNA mutation
      detection in cancer.
AB  - Allele-specific amplification, combined with TaqMan probe real-time polymerase
      chain reaction (real-time AS-PCR), has been widely used for detecting genetic
      variants, single nucleotide polymorphisms, and genetic mutations. In addition,
      several probe-blocking methods have been introduced in real-time AS-PCR to block
      amplification of wild-type templates and to increase detection sensitivity and
      specificity. However, most of these methods provide a limited sensitivity of no
      better than 1% and are complex in design of blockers, and thus cannot be readily
      adapted for different mutation assays. We have developed a modified non
      extendable primer blocker (NEPB) for real-time AS-PCR (AS-NEPB-PCR). The NEPB
      method provides an easy design of allele-specific primer and corresponding primer
      blocker that can be used in any single nucleotide polymorphism or mutation
      detection, specifically in the detection of low-frequency mutations. The method
      is straight-forward in assay optimization and can achieve 0.1% sensitivity with
      100% specificity (95% confidence interval, 92-100%) in detecting K-Ras, B-Raf,
      and EGFR mutations in cancer cells.

PMID- 23159591
TI  - APC germline mutations in individuals being evaluated for familial adenomatous
      polyposis: a review of the Mayo Clinic experience with 1591 consecutive tests.
AB  - Inactivating APC mutations cause familial adenomatous polyposis, classically
      characterized by hundreds to thousands of adenomatous colorectal polyps and
      cancer. Historically, 98% of pathogenic alterations in APC are nonsense or
      frameshift mutations; however, few reported series have used techniques that test
      for large deletions or duplications. Splice site mutations are only rarely
      documented. Consecutive cases (n = 1591) submitted for complete APC gene analysis
      during a 4-year period were reviewed. Testing included mutation screening (Sanger
      sequencing or conformation sensitive gel electrophoresis and protein truncation
      testing) with reflex confirmation sequencing. Gene deletion or duplication
      analysis was performed in 1421 cases by multiplex ligation-dependent probe
      amplification. Testing yielded 411 pathogenic, 20 likely pathogenic, 15 variant
      of uncertain significance, 140 likely benign, and 1005 negative reports.
      Identified were 168 novel variants (103 pathogenic, 5 likely pathogenic, 12
      variant of uncertain significance, and 48 likely benign). Of the 431 pathogenic
      or likely pathogenic mutations, frameshift, nonsense, splice site, and large
      deletion or duplication mutations represented 43%, 42%, 9%, and 6% of cases,
      respectively. This is the largest report of clinical APC testing experience with
      concurrent multiplex ligation-dependent probe amplification. In addition to
      nonsense and frameshift mutations, large deletions or duplications and canonical
      splice site mutations are a significant cause of familial adenomatous polyposis.
      Despite technological advances, broad allelic, locus, and phenotypic
      heterogeneity continue to pose challenges for genetic testing of patients with
      colorectal adenomatous polyposis.

PMID- 23159592
TI  - Novel heat pulse extension-PCR-based method for detection of large CTG-repeat
      expansions in myotonic dystrophy type 1.
AB  - Myotonic dystrophy type 1 (DM1) is an autosomal-dominant disease caused by an
      expansion of CTG repeats in the 3' untranslated region of the Dystrophia
      Myotonica Protein Kinase (DMPK) gene. Detection and accurate sizing of the CTG
      repeat expansions is clinically important, because the number of CTG repeats
      correlates with the disease severity. Because difficulties in PCR amplification
      over large expansions, molecular diagnosis of DM1 is still primarily based on
      Southern blotting, which is technically demanding and time consuming and requires
      large amounts of genomic DNA samples. We have recently discovered that the use of
      multiple heat pulses during Heat Pulse Extension PCR (HPE-PCR) enables efficient
      amplification over repetitive and GC-rich sequences. Based on this principle, we
      have developed an assay for efficient amplification of large CTG-repeat
      expansions seen in DM1 patients. The HPE-PCR method was able to amplify different
      DMPK1 repeat expansions of up to 1750 CTG repeats in 78 clinical samples with a
      varying degree of tissue heterogeneity, even in the presence of the short wild
      type allele. The CTG-repeat lengths and fragmentation patterns obtained with HPE
      PCR were fully concordant with the original diagnostic Southern blotting results.
      This novel technique provides a PCR-based platform for molecular diagnosis of
      DM1, and it has been adopted for routine diagnostic use.

PMID- 23159593
TI  - Evaluation of BRAF mutation testing methodologies in formalin-fixed, paraffin
      embedded cutaneous melanomas.
AB  - Patients diagnosed with BRAF V600E mutated cutaneous melanoma show response to
      treatment with the BRAF inhibitor Vemurafenib. Different methods for BRAF
      mutation detection exist; however, only the Cobas 4800 BRAF V600 Mutation Test
      has been approved by the US Food and Drug Administration for patient selection.
      The results from this test depend on the percentage of tumor cells in the
      samples, which clinically may be estimated with substantial variation. We have
      evaluated five different methods: the Cobas test, Sanger sequencing,
      pyrosequencing, TaqMan-based allele-specific PCR, and Competitive Amplification
      of Differentially Melting Amplicons (CADMA), for detection of BRAF c.1799T>A
      (V600E) mutations in 28 formalin-fixed paraffin-embedded (FFPE) cutaneous
      melanoma samples. We show that the frequency of the BRAF V600E mutation is
      influenced by the analytical sensitivity of the applied method. However, a 100%
      consensus was observed among all five methods when the tumor tissue fraction was
      more than 10% of all tissue or more than 50% of cell-dense tissue. When using
      Sanger sequencing, pyrosequencing, or the Cobas test, it may be advisable to
      perform macrodissection before mutation testing if the tumor cell fraction is
      low. CADMA and TaqMan may not require macrodissections for a reliable test.
      Therefore, the use of more sensitive methods may have a future in testing for
      BRAF mutations in clinical settings.

PMID- 23159594
TI  - Multiplex bead suspension array for screening Neisseria gonorrhoeae antibiotic
      resistance genetic determinants in noncultured clinical samples.
AB  - The increasing threat of antibiotic-resistant Neisseria gonorrhoeae highlights
      the need for new diagnostic options. A high-throughput multiplex bead suspension
      array assay was developed for profiling 29 N. gonorrhoeae genomic mutations and 2
      plasmid genes conferring resistance to 6 antimicrobial agents: penicillin,
      ciprofloxacin, cefixime, tetracycline, azithromycin, and spectinomycin. The three
      steps of this assay include amplification of 12 N. gonorrhoeae chromosomal and
      plasmid loci, multiplex allele-specific primer extension reaction, and multiplex
      bead suspension array detection. Antibiotic resistance genetic determinants were
      identified successfully in 239 cervicovaginal N. gonorrhoeae-positive noncultured
      swab samples. This molecular assay can be used for detection of gonococci in
      clinical specimens, molecular typing, mutation profiling, and predictive
      assessment of N. gonorrhoeae susceptibility to antibiotics without the need for
      culture.

PMID- 23159595
TI  - Detection of FLT3 internal tandem duplication in targeted, short-read-length,
      next-generation sequencing data.
AB  - A recurrent somatic mutation frequently found in cytogenetically normal acute
      myeloid leukemia (AML) is internal tandem duplication (ITD) in the fms-related
      tyrosine kinase 3 gene (FLT3). This mutation is generally detected in the
      clinical laboratory by PCR and electrophoresis-based product sizing. As the
      number of clinically relevant somatic mutations in AML increases, it becomes
      increasingly attractive to incorporate FLT3 ITD testing into multiplex assays for
      many somatic mutations simultaneously, using next-generation sequencing (NGS).
      However, the performance of most NGS analysis tools for identifying medium-size
      insertions such as FLT3 ITD mutations is largely unknown. We used a multigene,
      targeted NGS assay to obtain deep sequence coverage (>1000-fold) of FLT3 and 26
      other genes from 22 FLT3 ITD-positive and 29 ITD-negative specimens to examine
      the performance of several commonly used NGS analysis tools for identifying FLT3
      ITD mutations. ITD mutations were present in hybridization-capture sequencing
      data, and Pindel was the only tool out of the seven tested that reliably detected
      these insertions. Pindel had 100% sensitivity (95% CI = 83% to 100%) and 100%
      specificity (95% CI = 88% to 100%) in our samples; Pindel provided accurate ITD
      insertion sizes and was able to detect ITD alleles present at estimated
      frequencies as low as 1%. These data demonstrate that FLT3 ITDs can be reliably
      detected in panel-based, next-generation sequencing assays.

PMID- 23159597
TI  - Loss of nucleosomal DNA condensation coincides with appearance of a novel nuclear
      protein in dinoflagellates.
AB  - BACKGROUND: The packaging, expression, and maintenance of nuclear genomes using
      histone proteins is a ubiquitous and fundamental feature of eukaryotic cells, yet
      the phylum Dinoflagellata has apparently abandoned this model of nuclear
      organization. Their nuclei contain permanently condensed, liquid crystalline
      chromosomes that seemingly lack histone proteins, and contain remarkably large
      genomes. The molecular basis for this reorganization is poorly understood, as is
      the sequence of evolutionary events that led to such radical change. We have
      investigated nuclear organization in the closest relative to dinoflagellates,
      Perkinsus marinus, and an early-branching dinoflagellate, Hematodinium sp., to
      identify early changes that occurred during dinoflagellate nuclear evolution.
      RESULTS: We show that P. marinus has a typical nuclear organization that is based
      on the four core histones. By the early divergence of Hematodinium sp., however,
      dinoflagellate genome size is dramatically enlarged, chromosomes are permanently
      condensed, and histones are scarcely detectable. In place of histones, we
      identify a novel, dominant family of nuclear proteins that is only found in
      dinoflagellates and, surprisingly, in a family of large algal viruses, the
      Phycodnaviridae. These new proteins, which we call DVNPs (dinoflagellate/viral
      nucleoproteins), are highly basic, bind DNA with similar affinity to histones,
      and occur in multiple posttranslationally modified forms. We find these proteins
      throughout all dinoflagellates, including early- and late-branching taxa, but not
      in P. marinus. CONCLUSIONS: Gain of a major novel family of nucleoproteins,
      apparently from an algal virus, occurred early in dinoflagellate evolution and
      coincides with rapid and dramatic reorganization of the dinoflagellate nucleus.

PMID- 23159596
TI  - The magnitude of global marine species diversity.
AB  - BACKGROUND: The question of how many marine species exist is important because it
      provides a metric for how much we do and do not know about life in the oceans. We
      have compiled the first register of the marine species of the world and used this
      baseline to estimate how many more species, partitioned among all major
      eukaryotic groups, may be discovered. RESULTS: There are ~226,000 eukaryotic
      marine species described. More species were described in the past decade
      (~20,000) than in any previous one. The number of authors describing new species
      has been increasing at a faster rate than the number of new species described in
      the past six decades. We report that there are ~170,000 synonyms, that 58,000
      72,000 species are collected but not yet described, and that 482,000-741,000 more
      species have yet to be sampled. Molecular methods may add tens of thousands of
      cryptic species. Thus, there may be 0.7-1.0 million marine species. Past rates of
      description of new species indicate there may be 0.5 +/- 0.2 million marine
      species. On average 37% (median 31%) of species in over 100 recent field studies
      around the world might be new to science. CONCLUSIONS: Currently, between one
      third and two-thirds of marine species may be undescribed, and previous estimates
      of there being well over one million marine species appear highly unlikely. More
      species than ever before are being described annually by an increasing number of
      authors. If the current trend continues, most species will be discovered this
      century.

PMID- 23159598
TI  - Apical-basal polarity proteins are required cell-type specifically to direct
      photoreceptor morphogenesis.
AB  - Insect photoreceptor function is dependent on precise placement of the
      rhabdomeres, elaborated apical domains specialized for capturing light, within
      each facet of a compound eye. In Diptera, an asymmetric arrangement of
      rhabdomeres, combined with a particular pattern of axonal connections, enhances
      light sensitivity through the principle of neural superposition. To achieve the
      necessary retinal geometry, different photoreceptors (R cells) have distinct
      shapes. The Crumbs and Bazooka complexes play critical roles in directing
      rhabdomere development, but whether they might direct cell-type-specific apical
      architectures is unknown. We demonstrate that while mutations in Bazooka complex
      members cause pleiotropic morphogenesis defects in all R cell subtypes, Crumbs
      (Crb) and Stardust (Sdt) function cell autonomously to direct early stages in
      rhabdomere assembly in specific subsets of R cells. This requirement is reflected
      in the cell-type-specific expression of Crb protein and demonstrates that Sdt and
      Crb can act independently to similar effect. These two genes are also required
      for zonula adherens (ZA) assembly but display an unusual pattern of cellular
      redundancy for this function, as each gene is required in only one of two
      adjoining cells. Our results provide a direct link between fate specification and
      morphogenetic patterning and suggest a model for ZA assembly.

PMID- 23159599
TI  - Layer-specific entrainment of gamma-band neural activity by the alpha rhythm in
      monkey visual cortex.
AB  - Although the mammalian neocortex has a clear laminar organization, layer-specific
      neuronal computations remain to be uncovered. Several studies suggest that gamma
      band activity in primary visual cortex (V1) is produced in granular and
      superficial layers and is associated with the processing of visual input.
      Oscillatory alpha band activity in deeper layers has been proposed to modulate
      neuronal excitability associated with changes in arousal and cognitive factors.
      To investigate the layer-specific interplay between these two phenomena, we
      characterized the coupling between alpha and gamma band activity of the local
      field potential in V1 of the awake macaque. Using multicontact laminar electrodes
      to measure spontaneous signals simultaneously from all layers of V1, we found a
      robust coupling between alpha phase in the deeper layers and gamma amplitude in
      granular and superficial layers. Moreover, the power in the two frequency bands
      was anticorrelated. Taken together, these findings demonstrate robust
      interlaminar cross-frequency coupling in the visual cortex, supporting the view
      that neuronal activity in the alpha frequency range phasically modulates
      processing in the cortical microcircuit in a top-down manner.

PMID- 23159600
TI  - Evolutionary shift from fighting to foraging in blind cavefish through changes in
      the serotonin network.
AB  - BACKGROUND: Within the species Astyanax mexicanus, there are several interfertile
      populations of river-dwelling sighted fish and cave-dwelling blind fish which
      have evolved morphological and behavioral adaptations, the origins of which are
      unknown. Here, we have investigated the neural, genetic, and developmental bases
      for the evolution of aggressive behavior in this teleost. RESULTS: We used an
      intruder-resident behavioral assay to compare aggressiveness quantitatively
      (attack counts) and qualitatively (pattern and nature of attacks) between the
      surface and cave populations of Astyanax. Using this paradigm, we characterize
      aggressive behavior in surface fish, bring support for the genetic component of
      this trait, and show that it is controlled by raphe serotonergic neurons and that
      it corresponds to the establishment of dominance between fish. Cavefish have
      completely lost such aggressive/dominance behavior. The few attacks performed by
      cavefish during the behavioral test instead correspond to food-seeking behavior,
      driven by the developmental evolution of their hypothalamic serotonergic
      paraventricular neurons, itself due to increased Sonic Hedgehog signaling during
      early forebrain embryogenesis. CONCLUSIONS: We propose that during evolution and
      adaptation to their cave habitat, cavefish have undergone a behavioral shift, due
      to modifications of their serotonergic neuronal network. They have lost the
      typical aggressive behavior of surface fish and evolved a food-seeking behavior
      that is probably more advantageous to surviving in the dark. We have therefore
      demonstrated a link between the development of a neuronal network and the likely
      adaptive behaviors it controls.

PMID- 23159601
TI  - Convergent evolution within an adaptive radiation of cichlid fishes.
AB  - The recurrent evolution of convergent forms is a widespread phenomenon in
      adaptive radiations (e.g., [1-9]). For example, similar ecotypes of anoles
      lizards have evolved on different islands of the Caribbean, benthic-limnetic
      species pairs of stickleback fish emerged repeatedly in postglacial lakes,
      equivalent sets of spider ecomorphs have arisen on Hawaiian islands, and a whole
      set of convergent species pairs of cichlid fishes evolved in East African Lakes
      Malawi and Tanganyika. In all these cases, convergent phenotypes originated in
      geographic isolation from each other. Recent theoretical models, however, predict
      that convergence should be common within species-rich communities, such as
      species assemblages resulting from adaptive radiations. Here, we present the most
      extensive quantitative analysis to date of an adaptive radiation of cichlid
      fishes, discovering multiple instances of convergence in body and trophic
      morphology. Moreover, we show that convergent morphologies are associated with
      adaptations to specific habitats and resources and that Lake Tanganyika's cichlid
      communities are characterized by the sympatric occurrence of convergent forms.
      This prevalent coexistence of distantly related yet ecomorphologically similar
      species offers an explanation for the greatly elevated species numbers in cichlid
      species flocks.

PMID- 23159602
TI  - Selectivity of LC-MS/MS analysis: implication for proteomics experiments.
AB  - The recent development of hybrid mass spectrometers with high resolution and
      accurate mass capabilities has opened new avenues in quantitative proteomics. A
      systematic study was performed to assess the quantification performances of a
      novel quadrupole-Orbitrap instrument operated in MS/MS mode (parallel reaction
      monitoring). It included the analyses of 35 isotopically labeled peptides spiked
      in urine samples to establish their dilution curves. The results were evaluated
      by replicating the analyses on a triple quadrupole instrument operated in
      selected reaction monitoring (SRM; often referred as multiple reaction
      monitoring, MRM) mode to assess and compare the gain in selectivity resulting
      from high resolution fragment ion analysis. The high resolving power dramatically
      increased the selectivity of measurements by separating ions of interest from
      interferences, which occurred in several cases, and thus improved the
      quantification performance. In addition, an experiment to assess the "co
      habitation" of fragment ions in specific regions of the LC-MS/MS spectral space
      of a complex proteome digest was carried out. The study included the evaluation
      of the fragmentation patterns acquired under various experimental conditions
      (i.e., quadrupole isolation windows and Orbitrap resolving powers) for more than
      200 peptides, which provided an experimental baseline to guide the development of
      methods for parallel reaction monitoring acquisition. This article is part of a
      Special Issue entitled: From protein structures to clinical applications.

PMID- 23159604
TI  - A vitamin D3 analog augmented interleukin-8 production by human monocytic cells
      in response to various microbe-related synthetic ligands, especially NOD2
      agonistic muramyldipeptide.
AB  - Active metabolite vitamin D(3), 1alpha,25-dihydroxyvitamin D(3), is a pleiotropic
      factor and exhibits various physiological functions, including immunomodulating
      activities. In this study, the possible regulation of innate immune responses of
      human monocytic cells by a vitamin D(3) analog was examined. Human monocytic THP
      1 cells were pre-treated with OCT, vitamin D(3) analog, 1alpha,25-dihydroxy-22
      oxavitamin D(3), followed by stimulation with various chemically synthesized Toll
      like receptors (TLR) and NOD1 and NOD2 ligands. OCT-treated cells produced more
      IL-8 than non-treated cells upon stimulation with various chemically-synthesized
      ligands: TLR2-agonistic lipopeptide (FSL-1), TLR3-agonistic poly I:C, TLR4
      agonistic lipid A (E. coli-type LA-15-PP), NOD1-agonistic FK565 and NOD2
      agonistic muramyldipeptide (MDP). Among the ligands, MDP was the highest inducer
      of IL-8 production in OCT-treated THP-1 cells, and IL-8 production increased
      depending on the treatment time until 72h. OCT up-regulated the expression of
      NOD2 in THP-1 cells, and OCT-treated cells exhibited higher activation of p38,
      JNK and ERK in the MAPK pathway, IkappaBalpha in the NF-kappaB pathway, and TAK1
      upstream in response to MDP than non-treated cells. Analysis using siRNA against
      NOD2 and inhibitors of specific signal molecules indicated that the existence of
      NOD2 and activation of the above signaling molecules are required for enhanced
      production of IL-8 in OCT-treated THP-1 cells. These findings suggested that
      NOD2, NF-kappaB and MAPK pathways are involved in the activity of OCT to augment
      the response of human monocytic cells to MDP.

PMID- 23159603
TI  - Inhibition of TAK1 by kamebakaurin in dendritic cells.
AB  - Kamebakaurin (KA) has anti-cancer and anti-inflammatory activities through direct
      inhibition of DNA-binding activity of nuclear factor-kappa B (NF-kappaB) p50. We
      suggest here another molecular target of KA by the use of lipopolysaccharide
      treated dendritic cells. In cell- and enzyme-based assays, KA directly inhibited
      autophosphorylation and kinase activity of TAK1, followed by the inhibition of
      TAK1-downstream signaling cascades, such as IKK phosphorylation-IkappaBalpha
      degradation-nuclear translocation of NF-kappaB, phosphorylation of MEK3/6-p38
      mitogen activated protein kinase (MAPK), and MKK4/7-c-Jun N-terminal kinase MAPK.
      These results demonstrated that TAK1 might be the direct molecular target of KA.

PMID- 23159605
TI  - 6b,11b-Dihydroxy-6b,11b-dihydro-7H-indeno[1,2-b]naphtho[2,1-d]furan-7-one (DHFO),
      a small molecule targeting NF-kappaB, demonstrates therapeutic potential in
      immunopathogenic chronic inflammatory conditions.
AB  - 6b,11b-Dihydroxy-6b,11b-dihydro-7H-indeno[1,2-b]naphtho[2,1-d]furan-7-one (DHFO),
      an easily synthesisable, orally bioavailable and relatively non-toxic small
      molecule synthesised in our lab, was previously reported to possess anti-oxidant,
      5-lipoxygenase inhibitory, anti-inflammatory and peripheral analgesic activities.
      The present work deals with exploration of DHFO's efficacy in immunopathogenic
      chronic inflammatory conditions - arthritis and allergy. In carrageenan-induced
      inflammatory air pouch, which resembles the arthritic synovium, DHFO effectively
      reduced inflammatory redness and swelling and neutrophil infiltration. In
      complete Freund's adjuvant-induced arthritis, DHFO significantly decreased paw
      oedema and nitrite levels with efficacy comparable to diclofenac. DHFO inhibited
      neutrophil activation (observed as decreased myeloperoxidase levels), in both the
      in vivo models of inflammation. Interestingly, DHFO did not ulcerate the
      gastrointestinal tract, while diclofenac was observed to be extremely
      ulcerogenic. In antigen-induced active and passive anaphylaxis (allergy) models,
      DHFO dose-dependently prevented mesenteric mast cell (MC) degranulation with
      efficacy comparable to ketotifen. DHFO also inhibited compound 48/80 (C48/80)
      induced paw oedema and peritoneal MC degranulation. DHFO stabilised p815 murine
      MCs stimulated by C48/80 and calcium ionophore-A23187, indicating an action
      downstream of calcium mobilisation. DHFO's anti-allergic mechanism could be two
      pronged involving (1) inhibition of IgE production and/or (2) MC stabilisation.
      DHFO inhibited lipopolysaccharide (LPS)-induced pro-inflammatory mediator release
      (ROS, NO, IL-6 levels) and COX2 expression in RAW264.7 murine macrophages.
      Protein expression studies confirmed DHFO's ability to reduce nuclear levels of
      NF-kappaB in LPS-stimulated macrophages. Thus, DHFO is a promising non
      ulcerogenic synthetic small molecule lead for immunopathogenic chronic
      inflammatory conditions.

PMID- 23159606
TI  - Increasing betaB1-crystallin sensitivity to proteolysis caused by the congenital
      cataract-microcornea syndrome mutation S129R.
AB  - Congenital hereditary cataract, which is mainly caused by the deposition of
      crystallins in light-scattering particles, is one of the leading causes of
      newborn blindness in human beings. Recently, an autosomal dominant congenital
      cataract-microcornea syndrome in a Chinese family has been associated with the
      S129R mutation in betaB1-crystallin. To investigate the underlying molecular
      mechanism, we examined the effect of the mutation on betaB1-crystallin structure
      and thermal stability. Biophysical experiments indicated that the mutation
      impaired the oligomerization of betaB1-crystallin and shifted the dimer-monomer
      equilibrium to monomer. Molecular dynamic simulations revealed that the mutation
      altered the hydrogen-bonding network and hydrophobic interactions in the subunit
      interface of the dimeric protein, which resulted in the opening of the tightly
      associated interacting sites to allow the infiltration of the solvent molecules
      into the interface. Despite the disruption of betaB1-crystallin assembly, the
      thermal stability of betaB1-crystallin was increased by the mutation accompanied
      by the reduction of thermal aggregation at high temperatures. Further analysis
      indicated that the mutation significantly increased the sensitivity of betaB1
      crystallin to trypsin hydrolysis. The digested fragments of the mutant were prone
      to aggregate and unable to protect betaA3-crystallin against aggregation. These
      results indicated that the thermal stability-beneficial mutation S129R in betaB1
      crystallin provided an excellent model for discovering molecular mechanisms apart
      from solubility and stability. Our results also highlighted that the increased
      sensitivity of mutated crystallins towards proteases might play a crucial role in
      the pathogenesis of congenital hereditary cataract and associated syndrome.

PMID- 23159607
TI  - Chemokines in tissue fibrosis.
AB  - Fibrosis or scarring of diverse organs and tissues is considered as a pathologic
      consequence of a chronically altered wound healing response which is tightly
      linked to inflammation and angiogenesis. The recruitment of immune cells, local
      proliferation of fibroblasts and the consecutive accumulation of extracellular
      matrix proteins are common pathophysiological hallmarks of tissue fibrosis,
      irrespective of the organ involved. Chemokines, a family of chemotactic
      cytokines, appear to be central mediators of the initiation as well as
      progression of these biological processes. Traditionally chemokines have only
      been considered to play a critical role in orchestrating the influx of immune
      cells to sites of tissue injury. However, within the last years, further aspects
      of chemokine biology including fibroblast activation and angiogenesis have been
      deciphered in tissue fibrosis of many different organs. Interestingly, certain
      chemokines appear to mediate common effects in liver, kidney, lung, and skin of
      various animal models, while others mediate tissue specific effects. These
      aspects have to be kept in mind when extrapolating data of animal studies to
      early human trials. Nevertheless, the further understanding of chemokine effects
      in tissue fibrosis might be an attractive approach for identifying novel
      therapeutic targets in chronic organ damage associated with high morbidity and
      mortality. This article is part of a Special Issue entitled: Fibrosis:
      Translation of basic research to human disease.

PMID- 23159608
TI  - Protocatechualdehyde possesses anti-cancer activity through downregulating cyclin
      D1 and HDAC2 in human colorectal cancer cells.
AB  - Protocatechualdehyde (PCA) is a naturally occurring polyphenol found in barley,
      green cavendish bananas, and grapevine leaves. Although a few studies reported
      growth-inhibitory activity of PCA in breast and leukemia cancer cells, the
      underlying mechanisms are still poorly understood. Thus, we performed in vitro
      study to investigate if treatment of PCA affects cell proliferation and apoptosis
      in human colorectal cancer cells and define potential mechanisms by which PCA
      mediates growth arrest and apoptosis of cancer cells. Exposure of PCA to human
      colorectal cancer cells (HCT116 and SW480 cells) suppressed cell growth and
      induced apoptosis in dose-dependent manner. PCA decreased cyclin D1 expression in
      protein and mRNA level and suppressed luciferase activity of cyclin D1 promoter,
      indicating transcriptional downregulation of cyclin D1 gene by PCA. We also
      observed that PCA treatment attenuated enzyme activity of histone deacetylase
      (HDAC) and reduced expression of HDAC2, but not HDAC1. These findings suggest
      that cell growth inhibition and apoptosis by PCA may be a result of HDAC2
      mediated cyclin D1 suppression.

PMID- 23159609
TI  - Role of rhodopsin N-terminus in structure and function of rhodopsin-bitter taste
      receptor chimeras.
AB  - The bitter taste receptors (T2Rs) belong to the G protein-coupled receptor (GPCR)
      superfamily. In humans, bitter taste sensation is mediated by 25 T2Rs. Structure
      function studies on T2Rs are impeded by the low-level expression of these
      receptors. Different lengths of rhodopsin N-terminal sequence inserted at the N
      terminal region of T2Rs are commonly used to express these receptors in
      heterologous systems. While the additional sequences were reported, to enhance
      the expression of the T2Rs, the local structural perturbations caused by these
      sequences and its effect on receptor function or allosteric ligand binding were
      not characterized. In this study, we elucidated how different lengths of
      rhodopsin N-terminal sequence effect the structure and function of the bitter
      taste receptor, T2R4. Guided by molecular models of T2R4 built using a rhodopsin
      crystal structure as template, we constructed chimeric T2R4 receptors containing
      the rhodopsin N-terminal 33 and 38 amino acids. The chimeras were functionally
      characterized using calcium imaging, and receptor expression was determined by
      flow cytometry. Our results show that rhodopsin N-terminal 33 amino acids enhance
      expression of T2R4 by 2.5-fold and do not cause perturbations in the receptor
      structure.

PMID- 23159610
TI  - Upregulation of ATBF1 by progesterone-PR signaling and its functional implication
      in mammary epithelial cells.
AB  - Progesterone (Pg) is an essential steroid hormone during mammary gland
      development and tumorigenesis, including the maintenance of epithelial
      stem/progenitor cells. Pg functions through interaction with the progesterone
      receptors (PR) and Pg-PR signaling is thought to be mediated by key transcription
      factors, which are largely unidentified. In this study, we have identified the
      ATBF1 transcription factor as a transcriptional target of Pg-PR signaling in
      mammary epithelial cells. Pg treatment dramatically increased ATBF1 expression at
      both mRNA and protein levels in cultured cells and mammary tissues. As expected,
      the induction of ATBF1 was PR-dependent, as it only occurred in PR-positive but
      not in PR-negative cells, and pretreatment with the Pg antagonist RU-486 or RNAi
      mediated knockdown of PR abolished the upregulation of ATBF1 by Pg. Promoter
      reporter and ChIP assays further showed that Pg-activated PR directly binds to
      the ATBF1 promoter to induce its transcription. Prevention of ATBF1 induction
      inhibited the function of Pg in promoting progenitor cell transition, as
      indicated by colony formation in a Matrigel culture assay and expression of stem
      cell markers CD49f and CD44. These findings suggest that ATBF1 plays a crucial
      role in the Pg-PR signaling pathway in mammary epithelial cells.

PMID- 23159611
TI  - Crystal structure of the single cystathionine beta-synthase domain-containing
      protein CBSX1 from Arabidopsis thaliana.
AB  - The single cystathionine beta-synthase (CBS) pair proteins from Arabidopsis
      thaliana have been identified as being a redox regulator of the thioredoxin (Trx)
      system. CBSX1 and CBSX2, which are two of the six Arabidopsis cystathione beta
      synthase domain-containing proteins that contain only a single CBS pair, have
      close sequence similarity. Recently, the crystal structure of CBSX2 was
      determined and a significant portion of the internal region was disordered. In
      this study, crystal structures of full-length CBSX1 and the internal loop deleted
      (Deltaloop) form are reported at resolutions of 2.4 and 2.2A, respectively. The
      structures of CBSX1 show that they form anti-parallel dimers along their central
      twofold axis and have a unique ~155 degrees  bend along the side. This is
      different from the angle of CBSX2, which is suggestive of the flexible nature of
      the relative angle between the monomers. The biochemical data that were obtained
      using the deletion as well as point mutants of CBSX1 confirmed the importance of
      AMP-ligand binding in terms of enhancing Trx activity.

PMID- 23159612
TI  - Long-chain acyl-CoA synthetase 4 is regulated by phosphorylation.
AB  - Long chain acyl CoA synthetase 4 (Acsl4) is a key enzyme in steroidogenesis. It
      participates in steroid synthesis through of arachidonic acid release and
      Steroidogenic Acute Regulatory protein (StAR) induction. Acsl4 prefers
      arachidonic acid as substrate and acts probably as a homodimer. In steroidogenic
      cells, it has been demonstrated that Acsl4 is a high turnover protein located
      mainly in mitochondrial-associated membrane fraction (MAM) bound to other
      proteins and that it is newly synthesized by hormone stimulation. The synthesis
      of Acsl4 constitutes an early step in steroidogenesis. In the steroid synthesis
      process, activation of kinases plays a very important role. For this reason, the
      aim of this work was to study Acsl4 as a possible phosphoprotein and try to
      elucidate the role of its phosphorylation. We have determined for the first time
      that Acsl4 is a phosphoprotein whose phosphorylation is hormone-dependent. We
      also demonstrated that Acsl4 acts effectively as a dimer and that phosphorylation
      occurs after dimer formation. Studies in vitro demonstrated that Acsl4 is a
      substrate of both PKA and PKC and its phosphorylation by these kinases regulates
      its activity.

PMID- 23159613
TI  - Transduced Tat-glyoxalase protein attenuates streptozotocin-induced diabetes in a
      mouse model.
AB  - Diabetes mellitus (DM) is characterized by hyperglycemia. Glyoxalase 1 (GLO) has
      considerable potential as a possible therapeutic agent for DM. However, the
      precise action of GLO remains unclear in DM. In this study, we examined the
      protective effects of GLO protein in a streptozotocin (STZ)-induced diabetes
      animal model using cell-permeable Tat-GLO protein. Purified Tat-GLO protein was
      efficiently transduced into RINm5F cells in a time- and dose-dependent manner and
      protected cells against sodium nitroprusside (SNP)-induced cell death and DNA
      fragmentation. Furthermore, Tat-GLO protein significantly inhibited blood glucose
      levels and altered the serum biochemical parameters in STZ-induced diabetic mice.
      These results demonstrate that transduced Tat-GLO protein protects pancreatic
      cells by the inhibition of STZ-mediated toxicity. Therefore, Tat-GLO protein
      could be useful as a therapeutic agent against DM.

PMID- 23159614
TI  - CCAAT/enhancer binding protein beta deletion increases mitochondrial function and
      protects mice from LXR-induced hepatic steatosis.
AB  - Drugs designed specifically to activate liver X receptors (LXRs) have beneficial
      effects on lowering cholesterol metabolism and inflammation but unfortunately
      lead to severe hepatic steatosis. The transcription factor CCAAT/enhancer binding
      protein beta (C/EBPbeta) is an important regulator of liver gene expression but
      little is known about its involvement in LXR-based steatosis and cholesterol
      metabolism. The present study investigated the role of C/EBPbeta expression in
      LXR agonist (T0901317)-mediated alteration of hepatic triglyceride (TG) and
      lipogenesis in mice. C/EBPbeta deletion in mice prevented LXR agonist-mediated
      induction of lipogenic gene expression in liver in conjunction with significant
      reduction of liver TG accumulation. Surprisingly, C/EBPbeta(-/-) mice showed a
      major increase in liver mitochondrial electron chain function compared to WT
      mice. Furthermore, LXR activation in C/EBPbeta(-/-) mice increased the expression
      of liver ATP-binding cassette transporter ABCG1, a gene implicated in cholesterol
      efflux and reducing blood levels of total and LDL-cholesterol. Together, these
      findings establish a central role for C/EBPbeta in the LXR-mediated steatosis and
      mitochondrial function, without impairing the influence of LXR activation on
      lowering LDL and increasing HDL-cholesterol. Inactivation of C/EBPbeta might
      therefore be an important therapeutic strategy to prevent LXR activation-mediated
      adverse effects on liver TG metabolism without disrupting its beneficial effects
      on cholesterol metabolism.

PMID- 23159615
TI  - Brain expression level and activity of HDAC6 protein in neurodegenerative
      dementia.
AB  - Histone deacetylase 6 (HDAC6) is a multifunctional cytoplasmic protein that plays
      an especially critical role in the formation of aggresomes, where aggregates of
      excess protein are deposited. Previous immunohistochemical studies have shown
      that HDAC6 accumulates in Lewy bodies in Parkinson's disease and dementia with
      Lewy bodies (DLB) as well as in glial cytoplasmic inclusions in multiple system
      atrophy (MSA). However, it is uncertain whether the level and activity of HDAC6
      are altered in the brains of patients with neurodegenerative dementia. In the
      present study, we demonstrated that the level of HDAC6 was not altered in the
      temporal cortex of patients with Alzheimer's disease and DLB in comparison with
      controls. In contrast, the level of HDAC6 was significantly increased in the
      temporal cortex of patients with frontotemporal lobar degeneration with TDP-43
      inclusions (FTLD-TDP) and in the cerebellar white matter of patients with MSA.
      However, the level of acetylated alpha-tubulin, one of the substrates of HDAC6,
      was not altered in FTLD-TDP and MSA relative to controls. These findings suggest
      that the induced level of HDAC6 in the brain is insufficient for manifestation of
      its activity in FTLD-TDP and MSA.

PMID- 23159616
TI  - The liver X receptor promotes macrophage differentiation and suppresses
      osteoclast formation in mouse RAW264.7 promyelocytic leukemia cells exposed to
      bacterial lipopolysaccharide.
AB  - Lipopolysaccharide (LPS), the principal component of Gram-negative bacterial cell
      walls, is a stimulator of osteoclastogenesis and thus a key factor in
      inflammatory bone loss. We have recently reported that the important cholesterol
      and inflammatory regulator, liver X receptor (LXRalpha/beta), can potently
      inhibit osteoclast formation from bone marrow-derived osteoclast precursors in a
      bacterial/LPS environment. In this manuscript, we further studied the effect of
      the LXR agonist GW3965 on osteoclast differentiation in RAW264.7 promyelocytic
      leukemia cells exposed to LPS. We found that not only did activation of the LXR
      potently inhibit the formation of TRAP-positive osteoclast-like cells, but
      promoted a population of TRAP-negative mononuclear cells with high phagocytic
      activity. We observed reduced expression of the osteoclast markers TRAP/Acp5,
      Ctsk, Calcr and Oscar after 3-4days of GW3965 treatment, coinciding with an
      increase in the expression of the anti-osteoclastogenic factor Irf8. Expression
      of the macrophage/phagocytic marker Cd68 was increased, however the "classical"
      macrophage markers F4/80 and Cd14 and the "alternatively" activated macrophage
      markers Tgfbeta and Il10 were not altered. Further, activation of LXR increased
      the expression of the macrophage survival gene AIM/SPalpha, a known LXR target
      gene, and osteoclast/macrophage-related markers (Mitf, Pu.1, Usf1/2, Ostm1 and
      Mfr). Although Akt phosphorylation was reduced, GW3965 seemed to act
      independently of MAPKs (p38, ERK, JNK) and NFkappaB, and had no inhibitory effect
      on cytokine expression (Tnfalpha, Il6, or Il1beta). Our results indicate that
      activation of the LXR not only inhibits the differentiation of osteoclast-like
      cells from RAW264.7 cells in a bacterial/LPS environment, but is also involved in
      the fate determination of myeloid progenitor cells into macrophages with high
      phagocytic capacity.

PMID- 23159617
TI  - The flavoprotein Tah18-dependent NO synthesis confers high-temperature stress
      tolerance on yeast cells.
AB  - Nitric oxide (NO) is a ubiquitous signaling molecule involved in the regulation
      of a large number of cellular functions. In the unicellular eukaryote yeast, NO
      may be involved in stress response pathways, but its role is poorly understood
      due to the lack of mammalian NO synthase (NOS) orthologues. Previously, we have
      proposed the oxidative stress-induced l-arginine synthesis and its physiological
      role under stress conditions in yeast Saccharomyces cerevisiae. Here, our
      experimental results indicated that increased conversion of l-proline into l
      arginine led to NO production in response to elevated temperature. We also showed
      that the flavoprotein Tah18, which was previously reported to transfer electrons
      to the Fe-S cluster protein Dre2, was involved in NO synthesis in yeast. Gene
      knockdown analysis demonstrated that Tah18-dependent NO synthesis confers high
      temperature stress tolerance on yeast cells. As it appears that such a unique
      cell protection mechanism is specific to yeasts and fungi, it represents a
      promising target for antifungal activity.

PMID- 23159618
TI  - Establishment of a human cell line stably overexpressing mouse Nip45 and
      characterization of Nip45 subcellular localization.
AB  - The nuclear factor of activated T cells, cytoplasmic, calcineurin dependent 2
      interacting protein, Nfatc2ip (Nip45), has been implicated as a crucial
      coordinator of the immune response and of cellular differentiation in humans and
      mice, and contains SUMO-like domains in its C-terminal region. However, the
      significance of its N-terminal region and its correlation to the SUMO
      modification pathway remain largely uncharacterized. In this study, a human
      cultured cell line was established, in which FLAG-tagged mouse Nip45 (FLAG
      mNip45) was stably overexpressed. Under standard, non-stressful conditions, we
      detected FLAG-mNip45 diffusely distributed in the nucleus. Intriguingly,
      proteasome inhibition by MG132 caused FLAG-mNip45, together with SUMOylated
      proteins, to localize in nuclear domains associated with promyelocytic leukemia
      protein. Finally, using an in vitro binding assay, we showed interaction of the N
      terminal region of mNip45 with both free SUMO-3 and SUMO-3 chains, indicating
      that Nip45 may, in part, exert its function via interaction with SUMO/SUMOylated
      proteins. Taken together, our study provides novel information on a poorly
      characterized mammalian protein and suggests that our newly established cell line
      will be useful for elucidating the physiological role of Nip45.

PMID- 23159619
TI  - Coupling to the surface of liposomes alters the immunogenicity of hepatitis C
      virus-derived peptides and confers sterile immunity.
AB  - We have previously demonstrated that antigens chemically coupled to the surface
      of liposomes consisting of unsaturated fatty acids were cross-presented by
      antigen presenting cells to cytotoxic T lymphocytes (CTLs). Liposomal form of
      immunodominant CTL epitope peptides derived from lymphocytic choriomeningitis
      virus exhibited highly efficient antiviral CTL responses in immunized mice. In
      this study, we coupled 15 highly conserved immunodominant CTL epitope peptides
      derived from hepatitis C virus (HCV) to the surface of liposomes. We also
      emulsified the peptides in incomplete Freund's adjuvant, and compared the immune
      responses of the two methods of presenting the peptides by cytotoxicity induction
      and interferon-gamma (IFN-gamma) production by CD8(+) T cells of the immunized
      mice. We noticed significant variations of the immunogenicity of each peptide
      between the two antigen delivery systems. In addition, the immunogenicity
      profiles of the peptides were also different from those observed in the mice
      infected with recombinant adenoviruses expressing HCV proteins as previously
      reported. Induction of anti-viral immunity by liposomal peptides was tested by
      the challenge experiments using recombinant vaccinia viruses expressing
      corresponding HCV epitopes. One D(b)-restricted and three HLA-A(*)0201-restricted
      HCV CTL epitope peptides on the surface of liposomes were found to confer
      complete protection to immunized mice with establishment of long-term memory.
      Interestingly, their protective efficacy seemed to correlate with the induction
      of IFN-gamma producing cells rather than the cytotoxicity induction suggesting
      that the immunized mice were protected through non-cytolytic mechanisms. Thus,
      these liposomal peptides might be useful as HCV vaccines not only for prevention
      but also for therapeutic use.

PMID- 23159621
TI  - A deeper analysis of the epitope/paratope of PLY-5, a mouse monoclonal antibody
      which recognises the conserved undecapeptide tryptophan-rich loop (ECTGLAWEWWR)
      of bacterial cholesterol-dependent cytolysins.
AB  - A previous study showed that the minimal epitope recognised by the PLY-5 mAb in
      the conserved undecapeptide Trp-rich loop of bacterial CDCs should consist of
      WEWWRT (Jacobs et al., 1999) [5]. Now, through immunoscreening of amino acid
      substitution analogues, it is concluded that the second Trp and the Arg residues
      are essential in the PLY-5 epitope. The E residue is an auxiliary epitope
      contributor. Antibody modelling and docking simulations provided support for
      these findings. For recognition by the antibody, the Trp-rich loop flipped out,
      mimicking the mechanism of membrane insertion. The displaced second Trp was seen
      to establish aromatic stacking interactions with aromatic residues of the
      antibody paratope and the notably extruded guanidium tip of the arginine residue
      mediated electrostatic interactions with well-exposed carboxylic groups of
      glutamic residues on the surface of the paratope. Thus, the epitope/paratope
      interaction is mainly mediated by aromatic and by ionic interactions.

PMID- 23159620
TI  - Metformin inhibition of mTORC1 activation, DNA synthesis and proliferation in
      pancreatic cancer cells: dependence on glucose concentration and role of AMPK.
AB  - Metformin, a widely used anti-diabetic drug, is emerging as a potential
      anticancer agent but the mechanisms involved remain incompletely understood.
      Here, we demonstrate that the potency of metformin induced AMPK activation, as
      shown by the phosphorylation of its substrates acetyl-CoA carboxylase (ACC) at
      Ser(79) and Raptor at Ser(792), was dramatically enhanced in human pancreatic
      ductal adenocarcinoma (PDAC) cells PANC-1 and MiaPaCa-2 cultured in medium
      containing physiological concentrations of glucose (5 mM), as compared with
      parallel cultures in medium with glucose at 25 mM. In physiological glucose,
      metformin inhibited mTORC1 activation, DNA synthesis and proliferation of PDAC
      cells stimulated by crosstalk between G protein-coupled receptors and insulin/IGF
      signaling systems, at concentrations (0.05-0.1 mM) that were 10-100-fold lower
      than those used in most previous reports. Using siRNA-mediated knockdown of the
      alpha(1) and alpha(2) catalytic subunits of AMPK, we demonstrated that metformin,
      at low concentrations, inhibited DNA synthesis through an AMPK-dependent
      mechanism. Our results emphasize the importance of using medium containing
      physiological concentrations of glucose to elucidate the anticancer mechanism of
      action of metformin in pancreatic cancer cells and other cancer cell types.

PMID- 23159622
TI  - Differential hepatic protein tyrosine nitration of mouse due to aging - effect on
      mitochondrial energy metabolism, quality control machinery of the endoplasmic
      reticulum and metabolism of drugs.
AB  - Aging is the inevitable fate of life which leads to the gradual loss of functions
      of different organs and organelles of all living organisms. The liver is no
      exception. Oxidative damage to proteins and other macromolecules is widely
      believed to be the primary cause of aging. One form of oxidative damage is
      tyrosine nitration of proteins, resulting in the potential loss of their
      functions. In this study, the effect of age on the nitration of tyrosine in mouse
      liver proteins was examined. Liver proteins from young (19-22 weeks) and old (24
      months) C57/BL6 male mice were separated using sodium dodecyl sulfate
      polyacrylamide gel electrophoresis (SDS-PAGE) and electroblotted onto
      nitrocellulose membranes. Proteins undergoing tyrosine nitration were identified
      using anti-nitrotyrosine antibody. Three different protein bands were found to
      contain significantly increased levels of nitrotyrosine in old mice (Wilconxon
      rank-sum test, p<0.05). Electrospray ionization liquid chromatography tandem mass
      spectrometry (ESI-LC-MS/MS) was used to identify the proteins in these bands,
      which included aldehyde dehydrogenase 2, Aldehyde dehydrogenase family 1,
      subfamily A1, ATP synthase, H(+) transporting, mitochondrial F1 complex, beta
      subunit, selenium-binding protein 2, and protein disulfide-isomerase precursor.
      The possible impairment of their functions can lead to altered hepatic activity
      and have been discussed.

PMID- 23159623
TI  - RPAP3 splicing variant isoform 1 interacts with PIH1D1 to compose R2TP complex
      for cell survival.
AB  - We previously characterized RNA polymerase II-associated protein 3 (RPAP3) as a
      cell death enhancer. Here we report the identification and characterization of
      splicing isoform of RPAP3, isoform 1 and 2. We investigated the interaction
      between RPAP3 and PIH1 domain containing protein 1 (PIH1D1), and found that RPAP3
      isoform 1, but not isoform 2, interacted with PIH1D1. Furthermore, knockdown of
      RPAP3 isoform 1 by small interfering RNA down-regulated PIH1D1 protein level
      without affecting PIH1D1 mRNA. RPAP3 isoform 2 potentiated doxorubicin-induced
      cell death in human breast cancer T-47 cells although isoform 1 showed no effect.
      These results suggest that R2TP complex is composed of RPAP3 isoform 1 for its
      stabilization, and that RPAP3 isoform 2 may have a dominant negative effect on
      the survival potency of R2TP complex.

PMID- 23159624
TI  - Insulin suppression of apolipoprotein B in McArdle RH7777 cells involves
      increased sortilin 1 interaction and lysosomal targeting.
AB  - Insulin suppresses secretion of very low density lipoprotein (VLDL)
      apolipoprotein (apo) B in primary rodent hepatocytes (RH) by favoring the
      degradation of B100, the larger form of apo B, through post-endoplasmic reticulum
      proteolysis. Sortilin 1 (sort1), a multi-ligand sorting receptor, has been
      proposed as a mediator of lysosomal B100 degradation by directing B100 in pre
      VLDL to lysosomes rather than allowing maturation to VLDL and secretion. The
      purpose of our studies was to investigate the role of sort1 in insulin-dependent
      degradation of apo B. Using liver derived McArdle RH7777 (McA) cells, we
      demonstrate that insulin suppresses VLDL B100 secretion via a
      phosphatidylinositide 3-kinase (PI3K) dependent process that is inhibitable by
      wortmannin in a fashion similar to RH. Using McA cells and in situ cross-linking,
      we demonstrate that insulin acutely (30min) stimulates the interaction of B100
      with sort1. The insulin-induced interaction of sort1-B100 is markedly enhanced
      when lysosomal degradation is inhibited by Bafilomycin A1 (BafA1), an inhibitor
      of lysosomal acidification. As BafA1 also prevents insulin suppressive effects on
      apo B secretion, our results suggest that sort1-B100 interaction stimulated by
      insulin transiently accumulates with BafA1 and favors B100 secretion by default.

PMID- 23159625
TI  - Zinc finger protein 131 inhibits estrogen signaling by suppressing estrogen
      receptor alpha homo-dimerization.
AB  - Steroid hormone estrogen elicits various physiological functions, many of which
      are mediated through two structurally and functionally distinct estrogen
      receptors, ERalpha and ERbeta. The functional role of zinc finger protein 131
      (ZNF131) is poorly understood, but it is assumed to possess transcriptional
      regulation activity due to the presence of a DNA binding motif. A few recent
      reports, including ours, revealed that ZNF131 acts as a negative regulator of
      ERalpha and that SUMO modification potentiates the negative effect of ZNF131 on
      estrogen signaling. However, its molecular mechanism for ERalpha inhibition has
      not been elucidated in detail. Here, we demonstrate that ZNF131 directly
      interacts with ERalpha, which consequently inhibits ERalpha-mediated trans
      activation by suppressing its homo-dimerization. Moreover, we show that the C
      terminal region of ZNF131 containing the SUMOylation site is necessary for its
      inhibition of estrogen signaling. Taken together, these data suggest that ZNF131
      inhibits estrogen signaling by acting as an ERalpha-co-repressor.

PMID- 23159626
TI  - Central and peripheral des-acyl ghrelin regulates body temperature in rats.
AB  - In the present study using rats, we demonstrated that central and peripheral
      administration of des-acyl ghrelin induced a decrease in the surface temperature
      of the back, and an increase in the surface temperature of the tail, although the
      effect of peripheral administration was less marked than that of central
      administration. Furthermore, these effects of centrally administered des-acyl
      ghrelin could not be prevented by pretreatment with [D-Lys3]-GHRP-6 GH
      secretagogue receptor 1a (GHS-R1a) antagonists. Moreover, these actions of des
      acyl ghrelin on body temperature were inhibited by the parasympathetic nerve
      blocker methylscopolamine but not by the sympathetic nerve blocker timolol. Using
      immunohistochemistry, we confirmed that des-acyl ghrelin induced an increase of
      cFos expression in the median preoptic nucleus (MnPO). Additionally, we found
      that des-acyl ghrelin dilated the aorta and tail artery in vitro. These results
      indicate that centrally administered des-acyl ghrelin regulates body temperature
      via the parasympathetic nervous system by activating neurons in the MnPO through
      interactions with a specific receptor distinct from the GHS-R1a, and that
      peripherally administered des-acyl ghrelin acts on the central nervous system by
      passing through the blood-brain barrier, whereas it exerts a direct action on the
      peripheral vascular system.

PMID- 23159627
TI  - Ca2+ influx-dependent refilling of intracellular Ca2+ stores determines the
      frequency of Ca2+ oscillations in fertilized mouse eggs.
AB  - On mammalian fertilization, long-lasting Ca(2+) oscillations are induced in the
      egg by the fusing spermatozoon. While each transient Ca(2+) increase in Ca(2+)
      concentration ([Ca(2+)]) in the cytosol is due to Ca(2+) release from the
      endoplasmic reticulum (ER), Ca(2+) influx from outside is required for Ca(2+)
      oscillations to persist. In this study, we investigated how Ca(2+) influx is
      interrelated to the cycle of Ca(2+) release and uptake by the intracellular
      Ca(2+) stores during Ca(2+) oscillations in fertilized mouse eggs. In addition to
      monitoring cytosolic [Ca(2+)] with fura-2, the influx rate was evaluated using
      Mn(2+) quenching technique, and the change in [Ca(2+)] in the ER lumen was
      visualized with a targeted fluorescent probe. We found that the influx was
      stimulated after each transient Ca(2+) release and then diminished gradually to
      the basal level, and demonstrated that the ER Ca(2+) stores once depleted by
      Ca(2+) release were gradually refilled until the next Ca(2+) transient to be
      initiated. Experiments altering extracellular [Ca(2+)] in the middle of Ca(2+)
      oscillations revealed the dependence of both the refilling rate and the
      oscillation frequency on the rate of Ca(2+) influx, indicating the crucial role
      of Ca(2+) influx in determining the intervals of Ca(2+) transients. As for the
      influx pathway supporting Ca(2+) oscillations to persist, STIM1/Orai1-mediated
      store-operated Ca(2+) entry (SOCE) may not significantly contribute, since
      neither known SOCE blockers nor the expression of protein fragments that
      interfere the interaction between STIM1 and Orai1 inhibited the oscillation
      frequency or the influx rate.

PMID- 23159628
TI  - Model membrane interaction and DNA-binding of antimicrobial peptide Lasioglossin
      II derived from bee venom.
AB  - Lasioglossins, a new family of antimicrobial peptide, have been shown to have
      strong antimicrobial activity with low haemo-lytic and mast cell degranulation
      activity, and exhibit cytotoxic activity against various cancer cells in vitro.
      In order to understand the active conformation of these pentadecapeptides in
      membranes, we have studied the interaction of Lasioglossin II (LL-II), one of the
      members of Lasioglossins family with membrane mimetic micelle
      Dodecylphosphocholine (DPC) by fluorescence, Circular Dichroism (CD) and two
      dimensional (2D) (1)H NMR spectroscopy. Fluorescence experiments provide evidence
      of interaction of the N-terminal tryptophan residue of LL-II with the hydrophobic
      core of DPC micelle. CD results show an extended chain conformation of LL-II in
      water which is converted to a partial helical conformation in the presence of DPC
      micelle. Moreover we have determined the first three-dimensional NMR structure of
      LL-II bound to DPC micelle with rmsd of 0.36A. The solution structure of LL-II
      shows hydrophobic and hydrophilic core formation in peptide pointing towards
      different direction in the presence of DPC. This amphipathic structure may allow
      this peptide to penetrate deeply into the interfacial region of negatively
      charged membranes and leading to local membrane destabilization. Further we have
      elucidated the DNA binding ability of LL-II by agarose gel retardation and
      fluorescence quenching experiments.

PMID- 23159629
TI  - Metavinculin: New insights into functional properties of a muscle adhesion
      protein.
AB  - Metavinculin is a muscle-specific splice variant of the ubiquitously expressed
      cytoskeletal adaptor protein vinculin. Both proteins are thought to be co
      expressed in all muscle types where they co-localize to microfilament-associated
      adhesion sites. It has been shown that a metavinculin-specific insertion of 68
      amino acids alters the biochemical properties of the five-helix bundle in the
      tail domain. Here, we demonstrate that the metavinculin-specific helix H1' plays
      an important role for protein stability of the tail domain, since a point
      mutation in this helix, R975W, which is associated with the occurrence of dilated
      cardiomyopathy in man, further decreases thermal stability of the metavinculin
      tail domain. In striated muscle progenitor cells (myoblasts), both, metavinculin
      and the R975W mutant show significantly reduced, albeit distinctive residency and
      exchange rates in adhesion sites as compared to vinculin. In contrast to previous
      studies, we show that metavinculin is localized in a muscle fiber type-dependent
      fashion to the costameres of striated muscle, reflecting the individual metabolic
      and physiological status of a given muscle fiber. Metavinculin expression is
      highest in fast, glycolytic muscle fibers and virtually absent in M.
      diaphragmaticus, a skeletal muscle entirely lacking fast, glycolytic fibers. In
      summary, our data suggest that metavinculin enrichment in attachment sites of
      muscle cells leads to higher mechanical stability of adhesion complexes allowing
      for greater shear force resistance.

PMID- 23159630
TI  - Role of sigma factor E in regulation of Salmonella Agf expression.
AB  - Expression of thin aggregative fimbriae (Agf) in Salmonella, which is responsible
      for bacterial cell adhesion to surfaces, aggregation, and formation of biofilms,
      is regulated by a complex mechanism. In order to identify gene(s) involved in the
      expression of Agf, the TnphoA transposon was introduced into Salmonella
      typhimurium chi8505 for random mutagenesis. Colonies showing a change from
      wrinkly-rough morphology to the smooth form were screened for candidates. Through
      multiple selection processes, a mutant, named S. typhimurium CK167 was selected
      as the final candidate. Analyses of the nucleotide sequences of TnphoA insertion
      site identified the insertion in rpoE gene. S. typhimurium CK178, a defined rpoE
      deletion mutant on chi8505, exhibited the same colony morphology as seen in
      CK167. The S. typhimurium CK178 strain expressed significantly reduced amounts of
      AgfD and showed modulated biofilm formation, demonstrating the role of RpoE in
      AgfD expression. To the best of our knowledge, this is the first report
      demonstrating that RpoE acts as a regulator in the expression of Agf in
      Salmonella.

PMID- 23159631
TI  - Blinking effect and the use of quantum dots in single molecule spectroscopy.
AB  - Luminescent semiconductor nanocrystals (quantum dots, QD) have unique photo
      physical properties: high photostability, brightness and narrow size-tunable
      fluorescence spectra. Due to their unique properties, QD-based single molecule
      studies have become increasingly more popular during the last years. However QDs
      show a strong blinking effect (random and intermittent light emission), which may
      limit their use in single molecule fluorescence studies. QD blinking has been
      widely studied and some hypotheses have been done to explain this effect. Here we
      summarise what is known about the blinking effect in QDs, how this phenomenon may
      affect single molecule studies and, on the other hand, how the "on"/"off" states
      can be exploited in diverse experimental settings. In addition, we present
      results showing that site-directed binding of QD to cysteine residues of proteins
      reduces the blinking effect. This option opens a new possibility of using QDs to
      study protein-protein interactions and dynamics by single molecule fluorescence
      without modifying the chemical composition of the solution or the QD surface.

PMID- 23159632
TI  - N-Acyl taurines trigger insulin secretion by increasing calcium flux in
      pancreatic beta-cells.
AB  - Pancreatic beta-cells secrete insulin in response to various stimuli to control
      blood glucose levels. This insulin release is the result of a complex interplay
      between signaling, membrane potential and intracellular calcium levels. Various
      nutritional and hormonal factors are involved in regulating this process. N-Acyl
      taurines are a group of fatty acids which are amidated (or conjugated) to taurine
      and little is known about their physiological functions. In this study, treatment
      of pancreatic beta-cell lines (HIT-T15) and rat islet cell lines (INS-1) with N
      acyl taurines (N-arachidonoyl taurine and N-oleoyl taurine), induced a high
      frequency of calcium oscillations in these cells. Treatment with N-arachidonoyl
      taurine and N-oleoyl taurine also resulted in a significant increase in insulin
      secretion from pancreatic beta-cell lines as determined by insulin release assay
      and immunofluorescence (p<0.05). Our data also show that the transient receptor
      potential vanilloid 1 (TRPV1) channel is involved in insulin secretion in
      response to N-arachidonoyl taurine and N-oleoyl taurine treatment. However our
      data also suggest that receptors other than TRPV1 are involved in the insulin
      secretion response to treatment with N-oleoyl taurine.

PMID- 23159633
TI  - Osteogenic differentiation of C2C12 myogenic progenitor cells requires the Fos
      related antigen Fra-1 - a novel target of Runx2.
AB  - Bone formation is a developmental process requiring the differentiation of
      mesenchymal stem cells into osteoblasts. It is established that Runx2 tightly
      regulates osteoblast differentiation and bone formation. Fos-related antigen Fra
      1 is an essential factor for bone formation. Current evidence does not support a
      relationship between Fra-1 and Runx2 in osteogenesis. Here, we explored the
      possibility that Runx2 regulates Fra-1 expression during osteogenic
      differentiation of C2C12 myogenic progenitor cells. Expression of Fra-1 was
      induced rapidly after activation of Runx2 in a Tet-on stable C2C12 cell-line
      (C2C12/Runx2(Dox) sub-line). Transient transfection assay showed that Runx2
      activates Fra-1 promoter-reporter activity, suggesting that Fra-1 may be a direct
      target of Runx2. To determine the minimal region of the Fra-1 promoter that was
      activated by Runx2, a series of Fra-1 promoter deletion constructs were made. By
      transient transfection assay, we defined the minimal region to the proximal 342
      bp (-84 to +258). Two potential Runx2-binding sites (at positions +139 and +208)
      were predicted within this region. Mutation of the Runx2 motif at position +208
      significantly decreased Fra-1 promoter activity compared to wild type, whereas
      mutation of Runx2 at position +139 had no effect. Electrophoretic mobility shift
      assay (EMSA) demonstrated the existence of one atypical Runx2-binding element at
      position +208, and chromatin immunoprecipitation (ChIP) assay revealed that Runx2
      bound to the native Fra-1 promoter in vivo via this site. Finally, forced
      expression of Fra-1 resulted in upregulation of alkaline phosphatase (ALP), a
      marker of early osteoblast differentiation. Together, these results indicate that
      Fra-1 is a direct target of Runx2 during osteogenic differentiation of C2C12
      myogenic progenitor cells.

PMID- 23159634
TI  - Recombinant VP1 protein expressed in Pichia pastoris induces protective immune
      responses against EV71 in mice.
AB  - Human enterovirus 71 (EV71) is one of the major causative agents of hand, foot
      and mouth disease and is also associated with serious neurological diseases in
      children. Currently, there are no effective antiviral drugs or vaccines against
      EV71 infection. VP1, one of the major immunogenic capsid proteins of EV71, is
      widely considered to be the candidate antigen for an EV71 vaccine. In this study,
      VP1 of EV71 was expressed as a secretory protein with an N-terminal histidine tag
      in the methylotrophic yeast Pichia pastoris, and purified by Ni-NTA affinity
      chromatography. Immunogenicity and vaccine efficacy of the recombinant VP1 were
      assessed in mouse models. The results showed that the recombinant VP1 could
      efficiently induce anti-VP1 antibodies in BALB/c mice, which were able to
      neutralize EV71 viruses in an in vitro neutralization assay. Passive protection
      of neonatal mice further confirmed the prophylactic efficacy of the antisera from
      VP1 vaccinated mice. Furthermore, VP1 vaccination induced strong
      lymphoproliferative and Th1 cytokine responses. Taken together, our study
      demonstrated that the yeast-expressed VP1 protein retained good immunogenicity
      and was a potent EV71 vaccine candidate.

PMID- 23159635
TI  - Activin type IB receptor signaling in prostate cancer cells promotes lymph node
      metastasis in a xenograft model.
AB  - Activin, a member of the transforming growth factor-beta family, has been known
      to be a growth and differentiating factor. Despite its pluripotent effects, the
      roles of activin signaling in prostate cancer pathogenesis are still unclear. In
      this study, we established several cell lines that express a constitutive active
      form of activin type IB receptor (ActRIBCA) in human prostate cancer cells,
      ALVA41 (ALVA-ActRIBCA). There was no apparent change in the proliferation of ALVA
      ActRIBCA cells in vitro; however, their migratory ability was significantly
      enhanced. In a xenograft model, histological analysis revealed that the
      expression of Snail, a cell-adhesion-suppressing transcription factor, was
      dramatically increased in ALVA-ActRIBCA tumors, indicating epithelial mesenchymal
      transition (EMT). Finally, mice bearing ALVA-ActRIBCA cells developed multiple
      lymph node metastases. In this study, we demonstrated that ActRIBCA signaling can
      promote cell migration in prostate cancer cells via a network of signaling
      molecules that work together to trigger the process of EMT, and thereby aid in
      the aggressiveness and progression of prostate cancers.

PMID- 23159637
TI  - Pipernonaline from Piper longum Linn. induces ROS-mediated apoptosis in human
      prostate cancer PC-3 cells.
AB  - The antiproliferation effects of pipernonaline, a piperine derivative, were
      investigated on human prostate cancer PC-3 cells. It inhibited growth of androgen
      independent PC-3 and androgen dependent LNCaP prostate cells in a dose-dependent
      (30-90 MUM) and time-dependent (24-48 h) manner. The growth inhibition of PC-3
      cells was associated with sub-G(1) and G(0)/G(1) accumulation, confirmed by the
      down-regulation of CDK2, CDK4, cyclin D1 and cyclin E, which are correlated with
      G(1) phase of cell cycle. Pipernonaline up-regulated cleavage of procaspase
      3/PARP, but did not change expression of proapoptotic bax and antiapoptotic bcl-2
      proteins. Its caspase-3 activation was confirmed by the caspase-3 assay kit. In
      addition, pipernonaline caused the production of reactive oxygen species (ROS),
      increase of intracellular Ca(2+), and mitochondrial membrane depolarization,
      which these phenomena were reversed by N-acetylcysteine, a ROS scavenger. The
      results suggest that pipernonaline exhibits apoptotic properties through ROS
      production, which causes disruption of mitochondrial function and Ca(2+)
      homeostasis and leads to its downstream events including activation of caspase-3
      and cleavage of PARP in PC-3 cells. This is the first report of pipernonaline
      toward the anticancer activity of prostate cancer cells, which provides a role
      for candidate agent as well as the molecular basis for human prostate cancer.

PMID- 23159636
TI  - Androgen receptor primes prostate cancer cells to apoptosis through down
      regulation of basal p21 expression.
AB  - The androgen receptor (AR) for the male hormone androgen plays an important role
      in regulation of cell survival or death depending on the nature of cellular
      context and extracellular stimuli. The pro-survival function of AR is mediated
      mainly by transcriptional regulation of its target genes. By contrast, the pro
      death function of AR can be transcription-dependent or -independent, although the
      underlying mechanism of the latter is incompletely understood. Here we report
      that, in androgen-independent prostate cancer cells, AR promotes UV-induced
      apoptosis through down-regulation of basal expression of p21 independently of its
      transcriptional activity. Down-regulation of basal p21 expression depends on AR N
      terminal interacting protein PIRH2, an E3 ligase for proteasomal degradation of
      p53. Silencing of PIRH2 up-regulates p53, which in turn activates p21
      transcription. Consistent with this, knockdown of PIRH2 suppresses UV-induced AR
      dependent apoptosis. Our data suggest that AR primes androgen-independent
      prostate cancer cells to DNA damage-induced apoptosis through the PIRH2-p53-p21
      axis.

PMID- 23159638
TI  - Anti-cancer versus cancer-promoting effects of the interleukin-17-producing T
      helper cells.
AB  - Research on T helper 17 (Th17) cells with regard to immunoediting has revealed
      elusive results. Whereas enhanced Th17 response and related molecules such as
      interleukin (IL)-17, IL-21, IL-22, IL-23 and STAT3 accompanied tumor induction
      and progression, finding that tumor growth/stage was negatively correlated with
      increased infiltration of Th17 cells in the tumor mass has prompted elucidation
      of various antitumor mechanisms elicited by Th17 and their related molecules. The
      pro-tumor efficacy of Th17 response included promotion of neutrophilia and
      induction of angiogenic (e.g. VEGF, MMP2 and MMP9) and anti-apoptotic factors
      (e.g. Bcl-XL), as well as expansion and activation of myeloid-derived suppressor
      cells, which facilitate generation of tumor-specific regulatory T cells. Other
      tumor immunogenic settings revealed anti-tumor pathways including induction of
      cytotoxic activity, expression of MHC antigens, the ability Th17 cells to reside
      within the tumor, and to convert into IFN-gamma producers. Notably, Th17 cell
      related molecules exert indirect pro- or anti-tumor effects via inducing viral
      persistence or mediating protective mechanisms against bacterial and viral
      infection. Herein, the recent literature revealing such immunoediting events
      mediated by Th17 cells and their associated molecules as delivered by various
      experimental regimens and observed in cancer patient are revised, with a focus on
      some proposed anti-cancer therapies.

PMID- 23159639
TI  - The impact of the CYP2C9 and VKORC1 polymorphisms on acenocoumarol dose
      requirements in a Romanian population.
AB  - AIM: To investigate the genotype-phenotype correlation in Romanian patients
      treated with acenocoumarol. MATERIAL AND METHODS: We studied 301 consecutive
      patients who required treatment with acenocoumarol, admitted within the Municipal
      Hospital of Cluj-Napoca and the Heart Institute "Niculae Stanciou" in Cluj-Napoca
      over a 3-year period. For each patient we recorded clinical parameters which
      could interfere with the achievement of stable therapeutic international
      normalized ratio (INR). We performed genetic analysis which consisted of
      genotyping the CYP2C9 gene and the VKORC1 gene. Patients were divided in three
      groups according to the acenocoumarol dose needed to reach a stable INR: the low
      dose group (<=7mg/week), the medium dose group (>7mg and <28mg/week) and the high
      acenocoumarol dose group (>28mg/week). RESULTS: We found that patients' age was
      significantly different between groups (p<0.001). No differences existed between
      groups regarding the pathologies which required anticoagulation therapy or the
      concomitant treatment. The following parameters increased the odds of receiving a
      low dose of acenocoumarol: patient's age over 65years (OR, 3.2; p=0.01; 95%CI:
      1.24-8.25), the presence of the CYP2C9*3 allele (OR, 3.4; p=0.006; 95%CI: 1.41
      8.34), and the GA or AA genotype of c.-1639G>A polymorphism of VKORC1 (OR, 6.5;
      p=0.01; 95%CI: 1.38-30.5; respectively OR, 11.6; p=0.003; 95%CI: 2.26-59.58). A
      high acenocoumarol dose was less likely to be administered to an elderly patient
      (OR, 0.24; p=0.001; 95%CI: 0.1-0.56) or to a patient with the GA or AA genotype
      (OR, 0.2; p<0.001; 95CI%: 0.09-0.45; respectively OR, 0.05; p=0.006; 95%CI: 0.007
      0.43). CONCLUSION: The stable therapeutic dose of acenocoumarol is dependent of
      patient's age, the presence of the CYP2C9*3 allele and the c.-1639G>A
      polymorphism of VKORC1.

PMID- 23159641
TI  - Nonalcoholic fatty liver disease: current and potential therapies.
AB  - Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic
      liver injury worldwide. It covers a wide spectrum of hepatic disorders ranging
      from simple steatosis, through steatohepatitis (steatosis with inflammation), to
      cirrhosis. The molecular and cellular mechanisms underlying hepatic injury in
      NAFLD are not clear. Several evidences suggest that multiple mechanisms including
      insulin resistance, oxidative stress, inflammation, and genetic factors interact
      to initiate the development of NAFLD. Despite that there is currently no approved
      drug therapy for NAFLD, many approaches appear to be beneficial. Insulin
      sensitizers, antioxidants and antiinflammatory agents showed promising effects.
      This review highlights the current as well as the potential therapies of NAFLD.

PMID- 23159642
TI  - Chronic fluvoxamine treatment changes 5-HT(2A/2C) receptor-mediated behavior in
      olfactory bulbectomized mice.
AB  - AIMS: Olfactory bulbectomy (OBX) in rodents represents a valuable experimental
      model of depression. This study was designed to shed further light on the impact
      of putative serotonergic neuronal degeneration in OBX mice and to assess the
      effect of a widely used antidepressant on serotonergic related behavioral changes
      induced by OBX. MAIN METHODS: Adult male ddY mice were subject to bilateral OBX
      or sham surgery. The serotonin (5-HT)(2A/2C) receptor agonist 2,5-dimethoxy-4
      iodoamphetamine (DOI) enhanced a head-twitch response (HTR) in OBX mice. Effects
      of 5-HT(2A), 5-HT(2C) antagonists and fluvoxamine were observed in OBX mice
      following DOI administration. KEY FINDINGS: The HTR elicited by the
      administration of DOI (0.5 mg/kg and 1 mg/kg, i.p.) was increased about twofold
      in OBX mice when compared with controls on the 14th day after the surgery. The
      injection of ketanserin (0.025 mg/kg, i.p.), a 5-HT(2A) receptor antagonist,
      inhibited the enhancement of the DOI-induced HTR after OBX. Likewise, the
      administration of SB 242084 (1 mg/kg, s.c.), a 5-HT(2C) receptor antagonist, also
      inhibited the DOI-induced HTR in OBX mice. Chronic but not acute treatment with
      the antidepressant fluvoxamine, a selective serotonin reuptake inhibitor (SSRI),
      suppressed the enhancement of DOI-induced HTR after OBX. SIGNIFICANCE: These
      findings indicate that OBX, and the subsequent degeneration of neurons projecting
      from the olfactory bulb, caused a supersensitivity of 5-HT(2A/2C) receptors which
      may be involved in symptoms of depression.

PMID- 23159640
TI  - Mitochondrial dynamics in neurodegeneration.
AB  - It has been only 15 years since studies began on the molecular mechanisms
      underlying mitochondrial fission and fusion using simple model organisms such as
      Drosophila, yeast, and Caenorhabditis elegans. Beyond the primary functions of
      mitochondrial fission and fusion in controlling organelle shape, size, and
      number, it became clear that these dynamic processes are also critical to
      regulating cell death, mitophagy, and organelle distribution. Now, studies
      suggest that prominent changes occur in mitochondrial dynamics in a broad array
      of neurodegenerative diseases, and there is substantial evidence suggesting a key
      role in disease pathogenesis because neurons are among the most energy-consuming
      cell types and have a highly developed cell shape. Here, we review the recent
      findings on mitochondrial dynamics in neurodegeneration.

PMID- 23159643
TI  - TRPM8 ion channel ligands for new therapeutic applications and as probes to study
      menthol pharmacology.
AB  - Since the discovery of the TRPM8 gene in 2001, the TRPM8 ion channel, better
      known as the 'cold receptor' has been the target of a significant effort from the
      pharmaceutical industry to produce small-molecule agonists and antagonists of
      this receptor for various therapeutic applications ranging from cancer and
      urological disorders to the treatment of cold hypersensitivity and pain.
      Recently, a number of clinical studies have implicated menthol, the natural
      ligand of TRPM8, in facilitating and maintaining cigarette smoking behavior,
      possibly through its counter-irritant effects. However, a pharmacological link
      between menthol's action via TRPM8 and nicotine addiction has not been yet been
      investigated. This review gives an overview of reported small-molecule TRPM8
      agonists and antagonists and discusses their efficacy in models of various
      disease states. These compounds may be useful pharmacological tools to
      investigate the effect of menthol on nicotine addiction.

PMID- 23159644
TI  - Trigeminal neuralgia without vascular conflict: strategies and outcomes when the
      culprit goes missing.

PMID- 23159645
TI  - Carpal tunnel syndrome: when excellent is not good enough.

PMID- 23159646
TI  - Headaches in children with moyamoya disease: does revascularization help?

PMID- 23159647
TI  - Intra-aortic balloon pump counterpulsation in aneurysmal subarachnoid hemorrhage.

PMID- 23159648
TI  - Lumbar injection of normal saline for the treatment of tonsillar herniation-an
      old technique revisited: general considerations about increased intracranial
      pressure.

PMID- 23159649
TI  - Florence Nightingale: light to illuminate the world from the woman with the
      lantern.
AB  - The Ottoman-Russian war of 1853 to 1855 was significant not only as a war, but
      also in response to a reflex from the West brought with itself novel approaches
      related to care of patients under severe health conditions. Florence Nightingale
      and her associates assigned at that time to care for soldiers in Istanbul who
      were severely ailing as a result of battle conditions were instrumental in the
      emergence of a hitherto unknown profession. This article examines the progress of
      events in the London-Istanbul axis that led to this development.

PMID- 23159650
TI  - One-step fixation of atlantoaxial rotatory subluxation: technical note and report
      of three cases.
AB  - OBJECTIVE: To describe a successful one-step intraoperative reduction of
      atlantoaxial rotatory subluxation (AARS) using neuromuscular blockade and
      intraoperative traction. METHODS: While the patient was undergoing continuous
      somatosensory evoked potential monitoring, crown halo traction was applied under
      general anesthesia. A muscle relaxant was administered, and an intraoperative
      computed tomography scan was performed using the O-arm Surgical Imaging System in
      the supine position verifying adequate reduction. The patient was placed in the
      prone position, and a repeat image was obtained verifying persistent reduction in
      the position that the patient would undergo dorsal fixation. Occipitocervical
      fixation was then performed. RESULTS: This technique was performed successfully
      in three pediatric patients with chronic AARS. There were no complications
      related to the procedure. CONCLUSIONS: Intraoperative traction and neuromuscular
      blockade achieved a one-step reduction before fixation for subacute and chronic
      irreducible AARS. This one-step reduction obviates preoperative traction, which
      is often inconvenient and not tolerated by pediatric patients. Successful
      reduction is also demonstrated in detail intraoperatively with three-dimensional
      imaging.

PMID- 23159651
TI  - A review of oscillating field stimulation to treat human spinal cord injury.
AB  - OBJECTIVE: To report the results of use of a human oscillating field stimulator
      (OFS) in a phase 1 trial of 14 human patients with complete motor and sensory
      spinal cord injury. METHODS: Entry criteria were complete spinal cord injury
      between C5 and T10 in patients 18-65 years old with no transection on magnetic
      resonance imaging. All patients received the National Acute Spinal Cord Injury
      Study III methylprednisolone protocol. Cord compression or instability was
      treated before entry. All patient injuries remained complete (based on American
      Spinal Cord Injury scoring) with no somatosensory evoked potentials (SSEPs) below
      the injury after surgery or for 48 hours. All patients were implanted with the
      OFS within 18 days. Patients were checked every 2 weeks after implantation. The
      OFS was explanted at 15 weeks. Independent neurologic examinations (American
      Spinal Cord Injury score, visual analog scale for pain, and SSEPs) were done at 6
      weeks, 6 months, and 1 year. Statistical analyses were done by Wilcoxon rank sum
      test and analysis of variance (ANOVA). RESULTS: There were no complications at
      insertion, and one wound infection occurred after explant for a 3.5% infection
      rate. One patient was lost to follow-up after 6 months. All 14 patients had a
      mean visual analog scale score of 8 at implant and 2 at 6 months, and 13 remained
      a mean score of 2 at 1 year. Mean improvement in light touch score at 1 year was
      25.9 points (ANOVA, P < 0.001; Wilcoxon, P = 0.02). Mean improvement in pinprick
      score at 1 year was 15.2 points (ANOVA, P < 0.001; Wilcoxon, P = 0.02). Mean
      improvement in motor score was 6.9 (ANOVA, P < 0.01; Wilcoxon, P = 0.02). Of
      eight patients with cervical cord injuries, six had improvement in arm SSEPs, and
      one recovered a tibial SSEP. Of six patients with thoracic injuries, one
      recovered an abnormal lower SSEP. CONCLUSIONS: Treatment of human spinal cord
      injury with an OFS is safe, reliable, and easy. Compared with National Acute
      Spinal Cord Injury Study III compliant paralyzed patients, our results suggest
      efficacy.

PMID- 23159652
TI  - Lesion procedures in psychiatric neurosurgery.
AB  - OBJECTIVE: Lesion procedures for psychiatric indications have a history that
      spans more than a century. This review provides a brief history of psychiatric
      surgery and addresses the most recent literature on lesion surgery for the
      treatment of anxiety and mood disorders. METHODS: Relevant data described in
      publications from the early 1900 s through the modern era regarding lesion
      procedures for psychiatric indications, both historical and current use, are
      reported. RESULTS: The early procedures of Burkhardt, Moniz, and Freeman are
      reviewed, followed by descriptions of the more refined techniques of Leksell,
      Knight, Foltz, White, and Kelly. The application of lesion procedures to
      obsessive-compulsive disorder, mood disorders, and addiction are discussed.
      CONCLUSIONS: Lesioning procedures have informed modern deep brain stimulation
      targets. Recent lesioning studies demonstrate the efficacy and durability of
      these procedures in severely disabled patients. Judicious application of these
      techniques should continue for appropriately selected patients with severe,
      refractory psychiatric disorders.

PMID- 23159653
TI  - Management strategies for patients with spinal synovial cysts.

PMID- 23159654
TI  - No movement, no cyst.

PMID- 23159655
TI  - Fish oil for subarachnoid hemorrhage--this is not snake oil.

PMID- 23159656
TI  - Overview of neurocysticercosis.

PMID- 23159657
TI  - Stereotactic radiosurgery for brainstem cavernous malformations.

PMID- 23159658
TI  - Prehistoric skull trepanation: clearly a worldwide phenomenon.

PMID- 23159659
TI  - The DECRA trial and decompressive craniectomy in diffuse traumatic brain injury:
      is decompression really ineffective?

PMID- 23159660
TI  - A role for centers of excellence in transsphenoidal surgery.

PMID- 23159661
TI  - The impact of military conflict in modern-day neurosurgical management.

PMID- 23159662
TI  - Ex vivo permeation characteristics of venlafaxine through sheep nasal mucosa.
AB  - Venlafaxine, a dual acting antidepressant is a new therapeutic option for chronic
      depression. Depression is a common mental disorder associated with the
      abnormalities in neuronal transport in the brain. Since the nose-to-brain pathway
      has been indicated for delivering drugs to the brain, we analyzed the transport
      of venlafaxine through sheep nasal mucosa. Transmucosal permeation kinetics of
      venlafaxine were examined using sheep nasal mucosa mounted onto static vertical
      Franz diffusion cells. Nasal mucosa was treated with venlafaxine in situ gel (100
      MUl; 1% w/v) for 7h. Amount of venlafaxine diffused through mucosa was measured
      using validated RP-HPLC method. After the completion of the study
      histopathological investigation of mucosa was carried out. Ex vivo studies
      through sheep nasal mucosa showed sustained diffusion of venlafaxine with 66.5%
      permeation in 7h. Transnasal transport of venlafaxine followed a non-Fickian
      diffusion process. Permeability coefficient and steady state flux were found to
      be 21.11*10(-3) cmh(-1) and 21.118 MUg cm(-2)h(-1) respectively. Cumulative
      amount permeated through mucosa at 7h was found to be 664.8 MUg through an area
      of 3.14 cm(2). Total recovery of venlafaxine at the end of the permeation study
      was 87.3% of initial dose distributed (i) at the mucosal surface (208.4 MUg;
      20.8%) and (ii) through mucosa (664.8 MUg; 66.5%). Histopathological examinations
      showed no significant adverse effects confirming that the barrier function of
      nasal mucosa remains unaffected even after treatment with venlafaxine in situ
      gel. Permeation through sheep nasal mucosa using in situ gel demonstrated a
      harmless nasal delivery of venlafaxine, providing new dimension to the treatment
      of chronic depression.

PMID- 23159663
TI  - Nano and microparticulate chitosan-based systems for antiviral topical delivery.
AB  - Acyclovir (ACV) is one of the drugs of choice for the treatment of epidermal,
      ocular or systemic herpetic infections. Nevertheless, its trans-mucosal limited
      absorption and the scarce contact time of the formulation with the mucosal
      surface - especially in the ocular mucosa - constitute a big limitation of the
      antiviral efficiency. The most effective way to solve these problems is to
      increase the quantity and the residence time of the drug over the ocular surface.
      In order to cope with all these requirements, micro-particles (MPs) and nano
      particles (NPs) containing ACV have been developed using cross-linked chitosan
      with tripolyphosphate (TPP) due to the biocompatibility, bio-adhesion ability and
      the potential power as penetration enhancer of this polymer. Particles were
      characterized by Fourier-transformed infrared (FTIR) spectroscopy, X-ray
      diffraction, SEM, Zeta potential and particle size. Encapsulation efficiency and
      release profiles in flow through diffusion cells were also determined. Besides
      the Slug Mucosal Irritation (SMI) assay has been applied as an alternative to the
      Draize test to predict the mucosal irritation of the selected formulation. FTIR
      and X-ray results suggested an electrostatic interaction ACV-Chitosan that made
      ACV be molecularly dispersed within the polymer matrix. Encapsulation efficiency
      was 75% for MP and 16% for NP. Release profiles in flow through diffusion cells
      were also determined. From the diffusion profiles, it was found that the amounts
      of ACV effectively diffused in 24h were 30, 430 and 80 MUg for the ACV solution,
      MP and NP respectively. SMI results showed that chitosan-based particles induced
      moderate irritation and mild tissue damage, what supposes that ACV-MP constitute
      a promising alternative for further development of an antiviral formulation.

PMID- 23159664
TI  - A novel permeation enhancer: N-succinyl chitosan on the intranasal absorption of
      isosorbide dinitrate in rats.
AB  - The purpose of this paper is to study the potential of N-succinyl chitosan as a
      novel permeation enhancer for the intranasal absorption of isosorbide dinitrate
      (ISDN). A series of N-succinyl chitosan (NSCS) with different degree of
      succinylation (DS) and molecular weight were synthesized. An in situ nasal
      perfusion technique in rats was utilized to investigate the effect of NSCS
      substitution degree, NSCS molecular weight and concentration on the intranasal
      absorption of ISDN. The absorption enhancing effect of NSCS was compared with
      that of chitosan. It was found that all the NSCS investigated improved the
      intranasal absorption of ISDN remarkably. Better promoting effect was observed
      for 0.1% NSCS 50 (63) compared with 0.5% chitosan 50. In nasal ciliotoxicity
      test, both NSCS and chitosan investigated showed good safety profiles.
      Thereafter, in vivo studies of the selected formulations were carried out in rats
      and the pharmacokinetic parameters were calculated and compared with that of
      intravenous injection. Both in situ and in vivo studies demonstrated that NSCS is
      more effective than chitosan in promoting intranasal absorption of ISDN. Taking
      both absorption enhancing and safety reason into account, we suggest NSCS is a
      promising intranasal absorption enhancer.

PMID- 23159665
TI  - A preclinical pharmacokinetic modeling approach to the biopharmaceutical
      characterization of immediate and microsphere-based sustained release pulmonary
      formulations of rifampicin.
AB  - A rifampicin-hydroxypropyl-beta-cyclodextrin (RIF-HPCD) complex solution and two
      RIF-loaded PLGA microspheres with slow or fast release rates were nebulized into
      the rat lungs for a comparative biopharmaceutical evaluation. A pharmacokinetic
      model was applied to model systemic RIF concentrations and to predict the RIF
      concentrations in the lung epithelial lining fluid (ELF). With intravenous RIF
      and nebulized RIF-HPCD, plasma profiles and predicted RIF ELF profiles were
      superimposed indicating that RIF diffused almost instantaneously through the
      broncho-alveolar barrier. 5h post administration RIF ELF predicted concentrations
      were in agreement with experimental concentrations determined using the broncho
      alveolar lavage (BAL) sampling method. Microsphere formulations resulted in
      different plasma concentration profiles, demonstrating RIF sustained release. The
      PK model predicted the ELF concentrations to be much higher with microspheres
      than with nebulized and IV RIF, over a prolonged time period, which was confirmed
      by BAL sampling. In conclusion this work demonstrated the benefit of using
      sustained-release microspheres administered as aerosols to maintain, over a
      prolonged time period, high levels of pulmonary concentrations of drugs
      characterized by a rapid absorption through the broncho-alveolar barrier.
      Moreover, PK modeling was a useful tool to build concentration-versus-time
      profiles in non-readily accessible ELF compartment and to assess the
      biopharmaceutical properties of aerosol formulations for lung delivery.

PMID- 23159666
TI  - Transferrin conjugation does not increase the efficiency of liposomal Foscan
      during in vitro photodynamic therapy of oesophageal cancer.
AB  - Photodynamic therapy (PDT) is based on the delivery of photocytotoxic agents to a
      target tissue, followed by irradiation. In order to increase the efficiency of
      PDT in oesophageal cancer therapy, polyethylene glycol (PEG)-grafted, transferrin
      (Tf)-conjugated liposome formulations of 5,10,15,20-tetra(m-hydroxyphenyl)chlorin
      (Foscan), a second-generation photosensitiser, were prepared. Expression of
      transferrin receptors (CD71) in the oesophageal cancer cell line, OE21, was
      confirmed by immunoblot and confocal laser scanning microscopy. The anti
      proliferative effect of Foscan liposomes was evaluated and compared with plain
      formulations (i.e., without Tf) as well as with free drug. In addition, the
      intracellular accumulation was studied using high content analysis. Surprisingly,
      delivering Foscan by transferrin-conjugated PEG-liposomes to oesophageal cancer
      cells did not improve the photocytotoxicity or the intracellular accumulation of
      Foscan when compared to unmodified liposomes or indeed free photosensitiser. Tf
      targeted drugs and drug delivery systems have shown improved the therapy of many
      cancers. Our study, however, did not corroborate these findings. If this is due
      to the tumour type, the choice of in vitro model or the delivery systems remains
      to be confirmed.

PMID- 23159667
TI  - A novel approach to improve the pharmacokinetic properties of 8-chloro-adenosine
      by the dual combination of lipophilic derivatisation and liposome formulation.
AB  - 8-Chloro-adenosine (8CA) has shown promise in hematologic and solid tumor models
      and is in a phase I clinical trial. However, 8CA is intensively metabolized
      shortly after i.v. administration, with a t(1/2beta) of approximately 1h. Many
      carriers have failed to encapsulate 8CA efficiently. To improve its
      pharmacokinetic properties, 8-chloro-adenosine-5'-O-stearate (8CAS), a lipophilic
      octadecanoyl analogue of 8CA, was synthesized and incorporated into pegylated
      liposomes. The liposomes, comprising egg phosphatidylcholine, cholesterol and
      poly (ethylene glycol) 2000-distearoyl phosphatidylethanolamine (PEG-DSPE), had
      mean diameters of approximately 100 nm and an entrapment efficiency of 69-86%.
      MTT assays showed that the cytotoxicity of 8CAS and its pegylated liposomes (8CAS
      PL) were retained, with IC(50) values of 1.0 MUM and 1.9 MUM at 72 h on MCF-7
      cells, respectively, slightly higher than that of 8CA (0.6 MUM). Pharmacokinetic
      studies in rats after i.v. injection showed that both 8CAS and 8 CAS-PL had
      increased elimination half-lives (t(1/2), 128.4, 249.2 vs. 74.7 min), decreased
      clearance rates (Cl, 0.0135, 0.00875 vs. 0.2398 L/min/kg) and increased area
      under the concentration-time curve (AUC(0-infinity), 741.4, 1163.6 vs. 42.0 mg
      min/L) compared to 8CA. No obvious hematological toxicity was seen for Kunming
      mice receiving i.v. 8CA or 8CAS-PL at a dosage of 10mg/kg daily. These results
      indicate that the lipophilic derivation of 8CA and the incorporation of 8CAS is
      an effective strategy to improve the bioavailability of 8CA.

PMID- 23159668
TI  - Effects of molecular weight on permeability and microstructure of mixed ethyl
      hydroxypropyl-cellulose films.
AB  - Films of ethyl cellulose (EC) and water-soluble hydroxypropyl cellulose (HPC) can
      be used for extended release coatings in oral formulations. The permeability and
      microstructure of free EC/HPC films with 30% w/w HPC were studied to investigate
      effects of EC molecular weight. Phase separation during film spraying and
      subsequent HPC leaching after immersion in aqueous media cause pore formation in
      such films. It was found that sprayed films were porous throughout the bulk of
      the films after water immersion. The molecular weight affected HPC leaching, pore
      morphology and film permeability; increasing the molecular weight resulted in
      decreasing permeability. A model to distinguish the major factors contributing to
      diffusion retardation in porous films showed that the trend in permeability was
      determined predominantly by factors associated with the geometry and arrangement
      of pores, independent of the diffusing species. The film with the highest
      molecular weight did, however, show an additional contribution from pore
      wall/permeant interactions. In addition, rapid drying and increasing molecular
      weight resulted in smaller pores, which suggest that phase separation kinetics
      affects the final microstructure of EC/HPC films. Thus, the molecular weight
      influences the microstructural features of pores, which are crucial for mass
      transport in EC/HPC films.

PMID- 23159669
TI  - TGF-beta as a therapeutic target in high grade gliomas - promises and challenges.
AB  - Transforming growth factor-beta (TGF-beta) is a cytokine with a key role in
      tissue homeostasis and cancer. TGF-beta elicits both tumor suppressive and tumor
      promoting functions during cancer progression, in a wide range of cancers. Here,
      we review the tumor promoting function of TGF-beta and its possible promise as a
      therapeutic target in high grade gliomas, including glioblastoma multiforme
      (GBM), a disease with very poor prognosis. TGF-beta signaling is highly active in
      high grade gliomas and elevated TGF-beta activity has been associated with poor
      clinical outcome in this deadly disease. Common features of GBMs include fast
      cell proliferation, invasion into normal brain parenchyma, hypoxia, high
      angiogenic - and immunosuppressive activity, characteristics that all have been
      linked to activation of the TGF-beta pathway. TGF-beta signaling has also been
      connected with the cancer stem cell (CSC) phenotype in GBM. CSCs represent a
      subset of GBM cells thought to be responsible for tumor initiation, progression
      and relapse of disease. Following the description of these different properties
      of TGF-beta signaling and the underlying mechanisms identified thus far, the
      promise of TGF-beta targeted therapy in malignant gliomas is discussed. Several
      drugs targeting TGF-beta signaling have been developed that showed potent
      antitumor activity in preclinical models. A number of agents are currently
      evaluated in early clinical studies in glioma patients. Available results of
      these studies are highlighted and a perspective on the promise of TGF-beta
      targeted therapy is given.

PMID- 23159670
TI  - Low abundance drug resistance variants in transmitted HIV drug resistance
      surveillance specimens identified using tagged pooled pyrosequencing.
AB  - HIV drug resistance (DR) testing using Sanger sequencing (SS) is limited by the
      inability of the method to identify low abundance drug resistance variants. The
      application of tagged pooled pyrosequencing (TPP) for HIV DR surveillance is
      described and the results compared with SS. HIV(+) serum specimens were genotyped
      using both SS and TPP. Surveillance drug resistance mutations were identified
      using SS and TPP consensus reads at multiple mixed base identification thresholds
      (MBITs). Drug resistance patterns were highly concordant between SS and TPP when
      the MBIT was set at 20%. DR mutations were detected in 7.1% of the subjects, with
      1.6% of individuals harboring resistance to NRTI, 3.3% NNRTI and 2.7% PI.
      Analyzing the TPP reads for each subject confirmed that drug resistance mutations
      with frequencies <20% were inconsistently detected by SS. Conversely, low
      abundance drug resistant variants were easily identified using TPP with mixed
      base identification threshold set at low value. In conclusion, at considerable
      savings when compared to commercial assays, TPP produces HIV DR profiles that are
      concordant with those from SS, furthermore, these same data can be used to
      identify low abundance drug resistant variants.

PMID- 23159671
TI  - Simultaneous detection, typing and quantitation of oncogenic human papillomavirus
      by multiplex consensus real-time PCR.
AB  - A consensus multiplex real-time PCR test (PT13-RT) for the oncogenic human
      papillomavirus (HPV) types 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59 and 66
      is described. The test targets the L1 gene. Analytical sensitivity is between 4
      and 400 GU (genomic units) in the presence of 500 ng of human DNA, corresponding
      to 75,000 human cells. HPV types are grouped into multiplex groups of 3 or 4
      resulting in the use of 4 wells per sample and permitting up to 24 samples per
      run (including controls) in a standard 96-well real-time PCR instrument. False
      negative results are avoided by (a) measuring sample DNA concentration to control
      that sufficient cellular material is present and (b) including HPV type 6 as a
      homologous internal control in order to detect PCR inhibition or competition from
      other (non-oncogenic) HPV types. Analysis time from refrigerator to report is 8
      h, including 2.5 h hands-on time. Relative to the HC2 test, the sensitivity and
      specificity were respectively 98% and 83%, the lower specificity being
      attributable to the higher analytical sensitivity of PT13-RT. To assess type
      determination comparison was made with a reversed line-blot test. Type
      concordance was high (kappa=0.79) with discrepancies occurring mostly in multiple
      positive samples.

PMID- 23159673
TI  - Replication of hepatitis E virus in three-dimensional cell culture.
AB  - Hepatitis E is an acute, viral hepatitis epidemic in developing regions, but
      which is detected with increasing frequency in sporadic form in developed
      regions. Pigs and possibly some other mammals are considered reservoirs of
      zoonotic infection with hepatitis E virus (HEV). However, whilst the relative
      significance of potential transmission routes from pigs to people is still
      unclear, the consumption of raw or undercooked pig meat has been implicated as a
      source of HEV infection. The lack of information about HEV zoonotic transmission
      is due in part to the difficulties of in vitro propagation of HEV. The Rotating
      Wall Vessel (RVW) has been described as a useful tool for the culture of cell
      lines in a 3-dimensional (3D) configuration. The aim of this work was to develop
      a 3D cell culture system for HEV to facilitate studies into the viability of
      virions contaminating pig tissues. This study, demonstrated that HEV can
      replicate efficiently in the RWV in human hepatoblastoma PLC/PRF/5 cells for up
      to 5 months not only by real time RT-PCR but also by detection of complete
      virions via electron microscopy. Furthermore, the replication of HEV progeny was
      observed by detecting HEV RNA by RT-PCR. The progeny were able to infect fresh 3D
      cultures, showing that this method is able to produce infectious hepatitis E
      virions.

PMID- 23159672
TI  - Development of a reverse transcription loop-mediated isothermal amplification
      assay for rapid detection of grass carp reovirus.
AB  - Reverse transcription loop-mediated isothermal amplification (RT-LAMP) is a gene
      amplification method that can amplify the RNA template by isothermal incubation.
      This paper reports a rapid and sensitive RT-LAMP method which was developed for
      the detection of grass carp reovirus (GCRV). The present study concluded the
      optimal conditions for the LAMP reaction of which the Mg(2+) concentrations in
      the reaction mixtures, the incubation temperature, and the reaction time are at
      8mM, 64 degrees C, and 30 min, respectively. The analytical sensitivity of the RT
      LAMP method was revealed as low as 7 copies of viral templates and 100-fold more
      sensitive than the published RT-PCR method. A visual inspection of in-tube LAMP
      products stained with a DNA fluorescent dye demonstrated that the positive and
      negative reactions exhibit distinct and different colors in daylight, which means
      that gel electrophoresis is not necessary to judge the positive or negative
      results. As the application of the method is rapid, easy, and no complicated
      instrument required, the GCRV-RT-LAMP method established in this study has great
      potential for the detection of GCRV in both the laboratory and the farm.

PMID- 23159674
TI  - Multiplex real-time PCR assays for the detection of group C rotavirus,
      astrovirus, and Subgenus F adenovirus in stool specimens.
AB  - Group C rotavirus (GCRV), astrovirus (AstV), and adenovirus (subgenus F AdenoV)
      are etiologic agents of acute nonbacterial gastroenteritis, which often
      represents community outbreaks. For the efficient detection of GCRV, AstV, and
      subgenus F AdenoV in stool specimens, a multiplex real-time PCR assay was
      developed to detect these three viruses simultaneously, with high sensitivity and
      specificity. In total, 8404 clinical specimens were collected between April 2008
      and March 2011 and tested for GCRV, AstV, and subgenus F AdenoV by the multiplex
      real-time PCR, as well as for norovirus (NoV), sapovirus (SaV), and group A
      rotavirus (GARV) by non-multiplex real-time PCR. Forty-one specimens were
      positive for GCRV, AstV, or subgenus F AdenoV, including 15 specimens that were
      also positive for NoV, SaV, or GARV. Multiple viruses were detected
      simultaneously in 29 out of 4596 (0.63%) specimens infected with at least one
      virus. The association rates of AstV and subgenus F AdenoV with other viruses
      were significantly higher than those of NoV, SaV, GARV, or GCRV.

PMID- 23159675
TI  - Expression of transferrin receptor 1, proliferating cell nuclear antigen,
      p27(Kip1) and calbindin in the fetal and neonatal feline cerebellar cortex.
AB  - Cerebellar cortices from feline fetuses with estimated gestational ages of 40
      66days and from kittens aged 2days to 2months, all negative for feline
      panleukopenia virus (FPV) infection, were analysed for expression of the
      transferrin receptor 1 (TrFR1), proliferating cell nuclear antigen (PCNA),
      p27(Kip1) and calbindin. TrFR1, the receptor used by FPV to enter target cells,
      was expressed in capillary endothelial cells in the cerebellum at all fetal
      stages investigated and in Purkinje cells of a 3-week-old kitten, but not in the
      neuroblasts in the external granule layer (EGL). PCNA was expressed in cells of
      the superficial layer of the EGL. The cyclin-dependent kinase inhibitor p27(Kip1)
      was expressed in cells of the deep layer of the EGL. Purkinje cells expressed
      calbindin from the earliest fetal stage investigated. Co-expression of PCNA and
      calbindin could not be demonstrated, indicating that feline Purkinje cells are
      post-mitotic from at least 40days gestation.

PMID- 23159677
TI  - In vitro analysis of muscle activity illustrates mediolateral decoupling of hind
      and mid foot bone motion.
AB  - Activity of the extrinsic ankle-foot muscles is typically described for the whole
      foot. This study determines if this muscle activity is also confirmed for
      individual foot segments defined in multi-segment foot models used for clinical
      gait analysis. Analysis of the individual bone motion can identify functional
      complexes within the foot and evaluates the influence of an altered foot position
      on muscle activity. A custom designed and built gait simulator incorporating
      pneumatic actuators is used to control the muscle force of six muscle groups in
      cadaveric feet. Measurements were performed in three static postures in which
      individual muscle force was incrementally changed. The motion of four bone
      embedded LED-clusters was measured using a Krypton motion capture system and
      resulting motion of calcaneus, talus, navicular and cuboid was calculated.
      Results indicate that primary muscle activity at bone level corresponds with that
      described for the whole foot. Secondary activity is not always coherent for bones
      within one segment: decoupling of the movement of medial and lateral foot bones
      is documented. Furthermore, secondary muscle activity can alter according to foot
      position. The observed medio-lateral decoupling of the foot bones dictates the
      need to extend some of the multi-segment foot models currently used in clinical
      gait analysis.

PMID- 23159676
TI  - Identification of feline panleukopenia virus proteins expressed in Purkinje cell
      nuclei of cats with cerebellar hypoplasia.
AB  - Parvoviruses depend on initiation of host cell division for their replication.
      Undefined parvoviral proteins have been detected in Purkinje cells of the
      cerebellum after experimental feline panleukopenia virus (FPV) infection of
      neonatal kittens and in naturally occurring cases of feline cerebellar
      hypoplasia. In this study, a parvoviral protein in the nucleus of Purkinje cells
      of kittens with cerebellar hypoplasia was shown by immunoprecipitation to be the
      FPV viral capsid protein VP2. In PCR-confirmed, FPV-associated feline cerebellar
      hypoplasia, expression of the FPV VP2 protein was demonstrated by
      immunohistochemistry in Purkinje cell nuclei in 4/10 cases and expression of the
      FPV non-structural protein NS1 was demonstrated in Purkinje cell nuclei in 5/10
      cases. Increased nuclear ERK1 expression was observed in several Purkinje cells
      in 1/10 kittens. No expression of the G1 and S mitotic phase marker proliferating
      cell nuclear antigen (PCNA) was evident in Purkinje cell nuclei. These results
      support the hypothesis that FPV is able to proceed far into its replication cycle
      in post-mitotic Purkinje cells.

PMID- 23159678
TI  - Age-related changes in spatiotemporal characteristics of gait accompany ongoing
      lower limb linear growth in late childhood and early adolescence.
AB  - Walking gait is generally held to reach maturity, including walking at adult-like
      velocities, by 7-8 years of age. Lower limb length, however, is a major
      determinant of gait, and continues to increase until 13-15 years of age. This
      study used a sample from the Fels Longitudinal Study (ages 8-30 years) to test
      the hypothesis that walking with adult-like velocity on immature lower limbs
      results in the retention of immature gait characteristics during late childhood
      and early adolescence. There was no relationship between walking velocity and age
      in this sample, whereas the lower limb continued to grow, reaching maturity at
      13.2 years in females and 15.6 years in males. Piecewise linear mixed models
      regression analysis revealed significant age-related trends in normalized
      cadence, initial double support time, single support time, base of support, and
      normalized step length in both sexes. Each trend reached its own, variable
      specific age at maturity, after which the gait variables' relationships with age
      reached plateaus and did not differ significantly from zero. Offsets in ages at
      maturity occurred among the gait variables, and between the gait variables and
      lower limb length. The sexes also differed in their patterns of maturation.
      Generally, however, immature walkers of both sexes took more frequent and
      relatively longer steps than did mature walkers. These results support the
      hypothesis that maturational changes in gait accompany ongoing lower limb growth,
      with implications for diagnosing, preventing, and treating movement-related
      disorders and injuries during late childhood and early adolescence.

PMID- 23159679
TI  - The role of foot morphology on foot function in diabetic subjects with or without
      neuropathy.
AB  - The aim of this study was to investigate the role of foot morphology, related
      with respect to diabetes and peripheral neuropathy in altering foot kinematics
      and plantar pressure during gait. Healthy and diabetic subjects with or without
      neuropathy with different foot types were analyzed. Three dimensional
      multisegment foot kinematics and plantar pressures were assessed on 120 feet: 40
      feet (24 cavus, 20 with valgus heel and 11 with hallux valgus) in the control
      group, 80 feet in the diabetic (25 cavus 13 with valgus heel and 13 with hallux
      valgus) and the neuropathic groups (28 cavus, 24 with valgus heel and 18 with
      hallux valgus). Subjects were classified according to their foot morphology
      allowing further comparisons among the subgroups with the same foot morphology.
      When comparing neuropathic subjects with cavus foot, valgus heel with controls
      with the same foot morphology, important differences were noticed: increased
      dorsiflexion and peak plantar pressure on the forefoot (P<0.05), decreased
      contact surface on the hindfoot (P<0.03). While results indicated the important
      role of foot morphology in altering both kinematics and plantar pressure in
      diabetic subjects, diabetes appeared to further contribute in altering foot
      biomechanics. Surprisingly, all the diabetic subjects with normal foot arch or
      with valgus hallux were no more likely to display significant differences in
      biomechanics parameters than controls. This data could be considered a valuable
      support for future research on diabetic foot function, and in planning preventive
      interventions.

PMID- 23159680
TI  - Both maintaining hope and preparing for death: effects of physicians' and nurses'
      behaviors from bereaved family members' perspectives.
AB  - CONTEXT: Both maintaining hope and preparing for the patient's death are
      important for families of terminally ill cancer patients. OBJECTIVES: The primary
      aim of this study was to clarify the level of the family's achievement of
      maintaining hope and preparing for death and the professional's behavior related
      to their evaluations. METHODS: A cross-sectional, anonymous, nationwide survey
      was conducted involving 663 bereaved families of cancer patients who had been
      admitted to 100 palliative care units throughout Japan. RESULTS: A total of 454
      family members returned the questionnaire (effective response rate, 68%).
      Overall, 73% of families reported that they could both maintain hope and prepare
      for the patient's death. The independent determinants of the family's agreement
      in reference to the professional's behavior are pacing the explanation with the
      family's preparation; coordinating patient and family discussions about
      priorities while the patient was in better condition; willingness to discuss
      alternative medicine; maximizing efforts to maintain the patient's physical
      strength (e.g., meals, rehabilitation); discussing specific, achievable goals;
      and not saying "I can no longer do anything for the patient." CONCLUSION: About
      20% of family members reported that they could neither "maintain hope nor prepare
      for death." A recommended care strategy for medical professionals could include
      1) discussing achievable goals and preparing for the future and pacing
      explanation with the family's preparation, 2) willingness to discuss alternative
      medicine, 3) maximizing efforts to maintain the patient's physical strength, and
      4) avoid saying they could do nothing further for the patient.

PMID- 23159681
TI  - Assessment and management of adult cancer pain: a systematic review and synthesis
      of recent qualitative studies aimed at developing insights for managing barriers
      and optimizing facilitators within a comprehensive framework of patient care.
AB  - CONTEXT: Cancer pain is a common, burdensome problem, which is not well managed
      despite evidence-based guidelines. OBJECTIVES: To develop insights for managing
      barriers and optimizing facilitators to adult cancer pain assessment and
      management within a comprehensive framework of patient care. METHODS: We
      undertook a systematic review and synthesis of qualitative studies. Medline,
      PsycINFO, Embase, AMED, CINAHL, and Sociological Abstracts were searched from May
      20 to 26, 2011. To be included, the articles had to be published in a peer
      reviewed journal since 2000; written in English; and report original qualitative
      studies on the perspectives of patients, their significant others, or health care
      providers. Article quality was rated using the checklist of Kitto et al. Thematic
      synthesis followed a three-stage approach using Evidence for Policy and Practice
      Information and Co-ordinating Centre-Reviewer 4 software: 1) free line-by-line
      coding of "Results," 2) organization into "descriptive" themes, and 3)
      development of "analytical" themes informative to our objective. At Stage 3, a
      conceptual framework was selected from the peer-reviewed literature according to
      prima facie "fit" for descriptive themes. RESULTS: Of 659 articles screened, 70
      met the criteria, reporting 65 studies with 48 patient, 19 caregiver, and 21
      health care provider samples. Authors rarely reported reflexivity or negative
      cases. Mead and Bower's model of patient-centered care accommodated 85% of the
      descriptive themes; 12% more related to the caregiver and service/system factors.
      Three themes could not be accommodated. CONCLUSION: Findings highlight the need
      to integrate patient/family education within improved communication,
      individualize care, use more nonpharmacological strategies, empower
      patients/families to self-manage pain, and reorganize multidisciplinary roles
      around patient-centered care and outcomes. These conclusions require validation
      via consensus and intervention trials.

PMID- 23159682
TI  - Psychosocial effects of cancer cachexia: a systematic literature search and
      qualitative analysis.
AB  - CONTEXT: Cancer cachexia is debilitating and affects most patients with advanced
      cancer. Because treatment options are poor, the psychosocial effects of cancer
      cachexia always should be assessed and psychosocial support provided. OBJECTIVES:
      To review the existing evidence of psychosocial effects of cancer cachexia with
      the aim of identifying factors that might be modified to improve outcomes.
      METHODS: We carried out a systematic literature search in MEDLINE and Embase. The
      search string included key words for the topics "advanced cancer," "cancer
      cachexia," and "psychosocial effects." Publications were selected by two
      reviewers. The search was complemented by a hand search. RESULTS: Nineteen
      studies were included. The available information revealed mechanisms leading to,
      various presentations of, and coping strategies for psychosocial effects of
      cancer cachexia in both patients and their carers. Not all those affected manage
      the effects of the condition constructively. A number of clinically important
      adverse reactions have been identified. The main causes for negative psychosocial
      effects are a lack of knowledge of the irreversible nature of cancer cachexia and
      unsuccessful attempts to increase body weight with altered patterns of
      nutritional intake. Depending on patients' and their carers' coping resources,
      psychosocial effects may escalate or decrease. Early identification of
      psychosocial effects creates the potential for psychosocial interventions that
      improve the quality of life of those affected. Our analysis engendered a broader
      conceptualization of the psychosocial effects of cancer cachexia, leading to a
      number of suggestions for psychosocial interventions with the potential for
      providing relief. CONCLUSION: The concept of psychosocial effects in cancer
      cachexia has the potential to sensitize health care professionals to cachexia
      related problems and inform their clinical management of the condition.

PMID- 23159684
TI  - Validity of an observation method for assessing pain behavior in individuals with
      multiple sclerosis.
AB  - CONTEXT: Pain is a common and complex experience for individuals who live with
      multiple sclerosis (MS) and it interferes with physical, psychological, and
      social function. A valid and reliable tool for quantifying observed pain
      behaviors in MS is critical to understand how pain behaviors contribute to pain
      related disability in this clinical population. OBJECTIVES: To evaluate the
      reliability and validity of a pain behavioral observation protocol in individuals
      who have MS. METHODS: Community-dwelling volunteers with MS (N=30), back pain
      (N=5), or arthritis (N=8) were recruited based on clinician referrals,
      advertisements, fliers, web postings, and participation in previous research.
      Participants completed the measures of pain severity, pain interference, and self
      reported pain behaviors and were videotaped doing typical activities (e.g.,
      walking and sitting). Two coders independently recorded frequencies of pain
      behaviors by category (e.g., guarding and bracing) and interrater reliability
      statistics were calculated. Naive observers reviewed videotapes of individuals
      with MS and rated their pain. The Spearman's correlations were calculated between
      pain behavior frequencies and self-reported pain and pain ratings by naive
      observers. RESULTS: Interrater reliability estimates indicated the reliability of
      pain codes in the MS sample. Kappa coefficients ranged from moderate
      (sighing=0.40) to substantial agreements (guarding=0.83). These values were
      comparable with those obtained in the combined back pain and arthritis sample.
      Concurrent validity was supported by correlations with self-reported pain (0.46
      0.53) and with self-reports of pain behaviors (0.58). Construct validity was
      supported by a finding of 0.87 correlation between total pain behaviors observed
      by coders and mean pain ratings by naive observers. CONCLUSION: Results support
      the use of the pain behavior observation protocol for assessing pain behaviors of
      individuals with MS. Valid assessments of pain behaviors of individuals with MS
      could lead to creative interventions in the management of chronic pain in this
      population.

PMID- 23159685
TI  - Community-based palliative care: the natural evolution for palliative care
      delivery in the U.S.
AB  - Palliative care in the U.S. has evolved from a system primarily reliant on
      community-based hospices to a combined model that includes inpatient services at
      most large hospitals. However, these two dominant approaches leave most patients
      needing palliative care-those at home (including nursing homes) but not yet ready
      for hospice-unable to access the positive impacts of the palliative care
      approach. We propose a community-based palliative care (CPC) model that spans the
      array of inpatient and outpatient settings in which palliative care is provided
      and links seamlessly to inpatient care; likewise, it would span the full
      trajectory of advanced illness rather than focusing on the period just before
      death. Examples of CPC programs are developing organically across the U.S. As our
      understanding of CPC expands, standardization is needed to ensure replicability,
      consistency, and the ability to relate intervention models to outcomes. A growing
      body of literature examining outpatient palliative care supports the role of CPC
      in improving outcomes, including reduction in symptom burden, improved quality of
      life, increased survival, better satisfaction with care, and reduced health care
      resource utilization. Furthermore the examination of how to operationalize CPC is
      needed before widespread implementation can be realized. This article describes
      the key characteristics of CPC, highlighting its role in longitudinal care across
      patient transitions. Distinguishing features include consistent care across the
      disease trajectory independent of diagnosis and prognosis; inclusion of
      inpatient, outpatient, long-term care, and at-home care delivery; collaboration
      with other medical disciplines, nursing, and allied health; and full integration
      into the health care system (rather than parallel delivery). 

PMID- 23159683
TI  - Reliability and validity of a tool to measure the severity of dysphagia: the Food
      Intake LEVEL Scale.
AB  - CONTEXT: Dysphagia is one of the most prevalent and distressing symptoms among
      palliative care patients, and a practical assessment tool is required.
      OBJECTIVES: The aim of this study was to examine the reliability and validity of
      a tool to measure the severity of dysphagia: the Food Intake LEVEL Scale (FILS),
      a 10-point observer-rating scale. METHODS: The inter- and intrarater reliability
      was evaluated by three clinicians in 30 patients using weighted kappa statistics.
      The convergent validity was evaluated by examining correlations of FILS with the
      Functional Oral Intake Scale (FOIS) and patient-reported satisfaction levels with
      oral intake. RESULTS: Weighted kappa coefficients for interrater reliability
      ranged from 0.70 to 0.90 and those for intrarater reliability ranged from 0.83 to
      0.90. The FILS score was highly associated with the FOIS (rho = 0.96-0.99) and
      patient-reported satisfaction (rho = 0.89). CONCLUSION: The FILS seems to have
      fair reliability and validity as a practical tool for assessing the severity of
      dysphagia. Further study on the reliability, validity, and sensitivity of the
      FILS compared with the FOIS is needed.

PMID- 23159686
TI  - Comparing the retrospective reports of fatigue using the Fatigue Symptom Index
      with daily diary ratings in women receiving chemotherapy for gynecologic cancer.
AB  - CONTEXT: Fatigue, one of the most common side effects of chemotherapy, is
      typically assessed via retrospective recall (e.g., over the past week). It is
      unknown how such retrospective recall of fatigue correlates with daily ratings
      among people receiving chemotherapy. OBJECTIVES: The current study compared
      fatigue recorded in daily diaries with retrospective ratings using the Fatigue
      Symptom Inventory (FSI) in patients receiving chemotherapy for gynecologic
      cancer. METHODS: During the week before and the week after their first infusion
      of chemotherapy, patients completed daily diaries at 10 AM, 2, and 6 PM and the
      FSI at the end of each week. RESULTS: FSI and diary ratings of peak, lowest, and
      average fatigue were significantly correlated (P < 0.001). When peak, end,
      average, and variance diary ratings were regressed separately on the average FSI
      item, each was significant pre-chemotherapy (P < 0.01) and post-chemotherapy (P <
      0.05). However, when entered into a stepwise regression model, only the average
      fatigue diary rating was retained, explaining 52% of the variance pre
      chemotherapy and 54% of the variance post-chemotherapy average FSI item (P <
      0.001). CONCLUSION: The FSI keyed to the past week accurately reflects daily
      ratings of fatigue among patients receiving chemotherapy. This study has
      important implications, as completing retrospective ratings of fatigue may be
      less burdensome for cancer patients than daily assessments.

PMID- 23159687
TI  - Memoir of "a good daughter".
AB  - This short memoir reflects on the experience of a "good daughter" caring for both
      parents through their late aging and deaths. The memoir contemplates their
      personalities as expressed in their aging and the "good daughter's" experience in
      the death room. Those on a similar journey, whether as travelers, guides, or
      witnesses, may draw comfort, perhaps reassurance, from this account.

PMID- 23159688
TI  - Routine bimanual pelvic examinations: practices and beliefs of US obstetrician
      gynecologists.
AB  - OBJECTIVE: Less-than-annual cervical cancer screening is now recommended for most
      US women, raising questions about the need for routine annual bimanual pelvic
      examinations. Little is known about clinicians' bimanual pelvic examination
      practices, their beliefs about its importance, or the reasoning underlying its
      performance in asymptomatic women. STUDY DESIGN: We conducted a nationwide survey
      of US obstetrician-gynecologists. Respondents (n = 521) reported their
      examination practices and beliefs based on vignettes for asymptomatic women
      across the lifespan. RESULTS: Nearly all obstetrician-gynecologists perform
      bimanual pelvic examinations in asymptomatic women across the lifespan, although
      it is viewed as less important for a newly sexually active 18-year-old. Reasons
      cited as very important included adherence to standard medical practices (45%),
      patient reassurance (49%), detection of ovarian cancer (47%), and identification
      of benign uterine (59%) and ovarian (54%) conditions. CONCLUSION: Obstetrician
      gynecologists perform bimanual pelvic examinations in the vast majority of
      asymptomatic women, but the importance placed on the examinations and reasons for
      conducting them vary.

PMID- 23159689
TI  - Prediction of intrapartum fetal compromise using the cerebroumbilical ratio: a
      prospective observational study.
AB  - OBJECTIVE: To investigate the use of the fetal cerebroumbilical ratio to predict
      intrapartum compromise in appropriately grown fetuses. STUDY DESIGN: A
      prospective observational study set at Queen Charlotte's and Chelsea hospital,
      London, UK. Fetal biometry and Doppler resistance indices were measured in 400
      women immediately before established labor. Labor was then managed according to
      local protocols and guidelines, and intrapartum and neonatal outcome details
      recorded. RESULTS: Infants delivered by cesarean section for fetal compromise had
      significantly lower cerebroumbilical ratios than those born by spontaneous
      vaginal delivery (1.52 vs 1.82, P <= .001). Infants with a cerebroumbilical ratio
      <10th percentile were 6 times more likely to be delivered by cesarean section for
      fetal compromise than those with a cerebroumbilical ratio >=10th percentile (odds
      ratio, 6.1; 95% confidence interval, 3.03-12.75). A cerebroumbilical ratio >90th
      percentile appears protective of cesarean section for fetal compromise (negative
      predictive value 100%). CONCLUSION: The fetal cerebroumbilical ratio can identify
      fetuses at high and low risk of a subsequent diagnosis of intrapartum compromise,
      and may be used to risk stratify pregnancies before labor.

PMID- 23159690
TI  - Cotton-tipped applicator test: validity and reliability in chronic pelvic pain.
AB  - OBJECTIVE: We sought to assess the concurrent validity and interrater reliability
      of the cotton-tipped applicator (CTA) test as a screening tool for diagnosis of
      cutaneous allodynia in patients with viscerally related chronic pelvic pain
      (CPP). STUDY DESIGN: We performed a prospective cohort comparative observational
      study of referred patients to a gynecology clinic with CPP. A total of 22 females
      with CPP were compared to 23 pain-free controls and 12 cyclic pain patients.
      Participants were evaluated by 2 clinicians. The CTA test was performed to detect
      the appearance of pain in dermatomes of T10-L1. RESULTS: Interrater reliability
      resulted in 98% agreement for the 3 study groups. CTA test showed 73% sensitivity
      and 100% specificity for differentiating patients with CPP from pain-free
      patients. CONCLUSION: The CTA test had excellent interrater reliability and
      concurrent validity for diagnosis of cutaneous allodynia in CPP patients with
      visceral diseases versus controls.

PMID- 23159691
TI  - Common postoperative pulmonary complications after hysterectomy for benign
      indications.
AB  - OBJECTIVE: The purpose of this study was to estimate the incidence of
      postoperative pulmonary complications after hysterectomy for benign indications.
      STUDY DESIGN: This was a retrospective cohort study of all women who underwent
      hysterectomy for benign indications at the Cleveland Clinic from Jan. 1, 2001, to
      Dec. 31, 2009. Exclusion criteria incorporated patients who underwent
      hysterectomy for premalignant or malignant conditions. Pulmonary complications
      were defined as postoperative pneumonia, respiratory failure, atelectasis, and
      pneumothorax based on International classification of diseases, ninth revision,
      codes. RESULTS: In the 9-year study period, 3226 women underwent hysterectomy for
      benign indications (abdominal, 38.4%; vaginal, 39.3%; laparoscopic, 22.3%). Ten
      of the 3226 women (0.3%; 95% confidence interval, 0.17-0.57%) who underwent
      hysterectomy were identified with postoperative pulmonary complications. Among
      the different types of hysterectomy, the incidence of pulmonary complications was
      not different (total abdominal hysterectomy, 0.9%; vaginal hysterectomy, 0.12%;
      laparoscopic hysterectomy, 0.9%; P = .8). CONCLUSION: The incidence of
      postoperative pulmonary complications after hysterectomy for benign indications
      is low.

PMID- 23159692
TI  - Trends in use of surgical mesh for pelvic organ prolapse.
AB  - OBJECTIVE: Limited data exist on the rates of pelvic organ prolapse procedures
      utilizing mesh. The objective of this study was to examine trends in vaginal mesh
      prolapse procedures (VMs), abdominal sacrocolpopexy (ASC), and minimally invasive
      sacrocolpopexy (MISC) from 2005 to 2010. STUDY DESIGN: We utilized deidentified,
      adjudicated health care claims data from across the United States from 2005 to
      2010. Among women 18 years old or older, we identified all mesh prolapse
      procedures based on current procedural terminology codes (57267 for VM, 57280 for
      ASC, and 57425 for MISC). VM procedures included all vaginal prolapse surgeries
      in which mesh was placed, whether in the anterior, apical, or posterior
      compartment. We estimated rates per 100,000 person-years (100,000 py) and 95%
      confidence intervals (CIs). RESULTS: During 78.5 million person-years of
      observation, we identified 60,152 mesh prolapse procedures, for a rate of 76.0
      per 100,000 py (95% CI, 73.6-78.5). Overall, VMs comprised 74.9% of these
      surgeries for an overall rate of 56.9 per 100,000 py (95% CI, 55.0-58.9). Rates
      of ASC and MISC were considerably lower at 12.0 per 100,000 py (95% CI, 11.6
      12.5) and 9.5 per 100,000 py (95% CI, 9.2-9.9), respectively. Among
      sacrocolpopexies, ASC was more common than MISC in 2005-2007; however, since
      2007, the rate of MISC has increased, whereas the rate of ASC has decreased.
      Regarding trends by age, VM was considerably more common than sacrocolpopexies at
      all ages, and ASC was more common than MISC in women older than 50 years.
      CONCLUSION: From 2005 to 2010, the rate of mesh prolapse procedures has
      increased, with vaginal mesh surgeries constituting the vast majority.

PMID- 23159693
TI  - A systematic review of randomized trials assessing human papillomavirus testing
      in cervical cancer screening.
AB  - Our objective was to assess the sensitivity and specificity of human
      papillomavirus (HPV) testing for cervical cancer screening in randomized trials.
      We conducted a systematic literature search of the following databases: MEDLINE,
      CINAHL, EMBASE, and Cochrane. Eligible studies were randomized trials comparing
      HPV-based to cytology-based screening strategies, with disease status determined
      by colposcopy/biopsy for participants with positive results. Disease rates
      (cervical intraepithelial neoplasia [CIN]2 or greater and CIN3 or greater),
      sensitivity, and positive predictive value were abstracted or calculated from the
      articles. Six studies met inclusion criteria. Relative sensitivities for
      detecting CIN3 or greater of HPV testing-based strategies vs cytology ranged from
      0.8 to 2.1. The main limitation of our study was that testing methodologies and
      screening/management protocols were highly variable across studies. Screening
      strategies in which a single initial HPV-positive test led to colposcopy were
      more sensitive than cytology but resulted in higher colposcopy rates. These
      results have implications for cotesting with HPV and cytology as recommended in
      the United States.

PMID- 23159694
TI  - Perinatal complications and long-term neurodevelopmental outcome of infants with
      intrauterine growth restriction.
AB  - OBJECTIVE: The objective of the study was to evaluate perinatal and long-term
      complications of fetuses with intrauterine growth restriction (IUGR) compared
      with constitutionally small for gestational age (SGA) ones. STUDY DESIGN: The
      outcome of infants with IUGR and SGA born at the Medical University Graz
      (Austria) between 2003 and 2009 was retrospectively analyzed. Group assignment
      was based on birthweight, Doppler ultrasound, and placental morphology. The
      primary outcome was neurodevelopmental delay at 2 years corrected age. The
      secondary outcomes were perinatal complications. RESULTS: We included 219 IUGR
      and 299 SGA infants for perinatal and 146 and 215 for long-term analysis. Fetuses
      with IUGR were delivered earlier (35 vs 38 weeks) and had higher rates of
      mortality (8% vs 1%; odds ratio [OR], 8.3) as well as perinatal complications
      (24.4% vs 1.0%; OR, 31.6). The long-term outcome was affected by increased risk
      for neurodevelopmental impairment (24.7% vs 5.6%; OR, 5.5) and growth delay
      (21.2% vs 7.4%; OR, 3.4). CONCLUSION: IUGR infants are subject to an increased
      risk for adverse short- and long-term outcome compared with SGA children.

PMID- 23159695
TI  - Obstetric complications among US women with asthma.
AB  - OBJECTIVE: We sought to characterize complications of pregnancy, labor, and
      delivery associated with maternal asthma in a contemporary US cohort. STUDY
      DESIGN: We studied a retrospective cohort based on electronic medical record data
      from 223,512 singleton deliveries from 12 clinical centers across the United
      States from 2002 through 2008. RESULTS: Women with asthma had higher odds of
      preeclampsia (adjusted odds ratio [aOR], 1.14; 95% confidence interval [CI], 1.06
      1.22), superimposed preeclampsia (aOR, 1.34; 95% CI, 1.15-1.56), gestational
      diabetes (aOR, 1.11; 95% CI, 1.03-1.19), placental abruption (aOR, 1.22; 95% CI,
      1.09-1.36), and placenta previa (aOR, 1.30; 95% CI, 1.08-1.56). Asthmatic women
      had a higher odds of preterm birth overall (aOR, 1.17; 95% CI, 1.12-1.23) and of
      medically indicated preterm delivery (aOR, 1.14; 95% CI, 1.01-1.29). Asthmatics
      were less likely to have spontaneous labor (aOR, 0.87; 95% CI, 0.84-0.90) and
      vaginal delivery (aOR, 0.84; 95% CI, 0.80-0.87). Risks were higher for breech
      presentation (aOR, 1.13; 95% CI, 1.05-1.22), hemorrhage (aOR, 1.09; 95% CI, 1.03
      1.16), pulmonary embolism (aOR, 1.71; 95% CI, 1.05-2.79), and maternal intensive
      care unit admission (aOR, 1.34; 95% CI, 1.04-1.72). CONCLUSION: Maternal asthma
      increased risk for nearly all outcomes studied in a general obstetric population.

PMID- 23159696
TI  - The association between urinary and fecal incontinence and social isolation in
      older women.
AB  - OBJECTIVE: To describe the association between social isolation and urinary
      incontinence and fecal incontinence in older women. METHODS: We conducted a
      secondary database analysis of the National Social Life, Health and Aging Project
      for women aged 57 to 85 years old. Our primary outcome was self-report of often
      feeling isolated. We explored self-report of daily urinary incontinence and
      weekly fecal incontinence. Two logistic regression analyses were performed to
      assess the association between often feeling isolated and (1) daily urinary
      incontinence and (2) weekly fecal incontinence. RESULTS: A total of 1412 women
      were included in our analysis. Daily urinary incontinence was reported by 12.5%
      (177/1412) of community-dwelling older women. More women with daily urinary
      incontinence reported often feeling isolated (6.6%; 95% confidence interval [CI],
      1.3-11.9 vs 2.6%; 95% CI, 1.7-3.5; P = .04) compared with women without daily
      urinary incontinence. Women with daily urinary incontinence had 3.0 (95% CI, 1.1
      7.6) increased odds of often feeling isolated after adjusting for depressive
      symptoms, age, race, education, and overall health. Weekly fecal incontinence was
      reported by 2.9% (41/1412) of women. Weekly fecal incontinence and often feeling
      isolated were associated on univariable analysis (crude odds ratio, 4.6; 95% CI,
      1.4-15.1). However, after adjusting for depressive symptoms, age, race,
      education, and overall health the association between weekly fecal incontinence
      and often feeling isolated was not significant (adjusted odds ratio, 0.65; 95%
      CI, 0.1-5.3; P = .65). CONCLUSION: After adjusting for confounders, daily urinary
      incontinence was significantly associated with often feeling isolated. Weekly
      fecal incontinence was not found to be associated with often feeling isolated on
      multivariable logistic regression.

PMID- 23159697
TI  - Fetal lung lesions: can we start to breathe easier?
AB  - OBJECTIVE: The purpose of this study was to develop a simple and accurate
      approach for risk stratification of fetal lung lesions that are associated with
      respiratory compromise at birth. STUDY DESIGN: We conducted a retrospective
      review of 64 prenatal lung lesions that were managed at a single fetal care
      referral center (2001-2011). Sonographic data were analyzed and correlated with
      perinatal outcomes. RESULTS: Hydrops occurred in only 4 cases (6.3%). Among
      fetuses without hydrops, the congenital pulmonary airway malformation volume
      ratio (CVR) was the only variable that was associated significantly with
      respiratory compromise and the need for lung resection at birth (P < .01). Based
      on a maximum CVR >1.0, the sensitivity, specificity, positive predictive value,
      and negative predictive value for respiratory morbidity were 90%, 93%, 75%, and
      98%, respectively. CONCLUSION: Nonhydropic fetuses with a maximum CVR >1.0 are a
      subgroup of patients who are at increased risk for respiratory morbidity and the
      need for surgical intervention. These patients should be delivered at a tertiary
      care center with pediatric surgery expertise to ensure optimal clinical outcomes.

PMID- 23159698
TI  - Hypertension and antihypertensive drugs in pregnancy and perinatal outcomes.
AB  - OBJECTIVE: Despite high rates of hypertension in pregnancy, the effects of
      hypertension have not been separated appropriately from the effects of the
      medications that are used. We evaluated the safety of exposure to
      antihypertensive medications during pregnancy, while accounting for disease
      effects. STUDY DESIGN: A population-based retrospective cohort study was
      performed that compared all pregnancies of women with hypertension who were
      either exposed or unexposed to antihypertensive medications. A computerized
      database of the medications that were dispensed to pregnant women from 1998-2008
      was linked with computerized databases that contained maternal and infant
      hospitalization records from the district hospital during the same period.
      RESULTS: During the study period, 100,029 deliveries occurred; of those, 1964
      pregnant women experienced chronic hypertension, and 620 neonates (0.6%) were
      exposed to at least 1 antihypertensive medication (methyldopa or atenolol) during
      pregnancy. A higher rate of intrauterine growth restriction (7.2% vs 2.1%,
      respectively; adjusted odds ratio [OR], 4.37; 95% confidence interval [CI], 3.00
      6.36; P < .001), small for gestational age (3% vs 1.7%, respectively; adjusted
      OR, 2.23; 95% CI, 1.27-3.92; P = .005), and preterm deliveries (<37 weeks, 22.9%
      vs 8.0%, respectively; adjusted OR, 3.69; 95% CI, 2.90-4.69; P < .001) were noted
      among the pregnancies of women who were exposed to antihypertensive medications
      during the third trimester. Importantly, a similar association was detected when
      we compared women with chronic hypertension who were not treated during pregnancy
      (n = 1074) to women who had no chronic hypertension and who were unexposed to
      antihypertensive medications (n = 97,820). CONCLUSION: Chronic hypertension with
      or without treatment during pregnancy is an independent and significant risk
      factor for adverse perinatal outcomes such as intrauterine growth restriction,
      small for gestational age, and preterm delivery.

PMID- 23159699
TI  - Psychosocial risk, prenatal counseling and maternal behavior: findings from
      PRAMS, 2004-2008.
AB  - OBJECTIVE: To determine the impact of prenatal counseling regarding psychosocial
      risk factors on maternal behavior. STUDY DESIGN: We analyzed data from 198,323
      women participating in the Pregnancy Risk Assessment Monitoring System (PRAMS).
      The chi(2) and logistic regression analyses assessed the relationship between
      psychosocial risk, prenatal counseling and maternal behavior. RESULTS: The odds
      of receiving risk-appropriate prenatal counseling were significantly greater for
      participants who used alcohol (odds ratio, 1.13; 95% confidence interval, 1.08
      1.17) and tobacco (odds ratio, 2.02; 95% confidence interval, 1.91-2.13). After
      receiving counseling, women quit using alcohol (72.9% vs 27.1%; P < .01) and
      tobacco (79.9% vs 20.1%; P < .01) at a significantly greater rate and women with
      unintended pregnancies were more likely to use postpartum contraception (83.6% vs
      16.4%; P < .01) than women who were not counseled. However, no significant
      differences were found in the rates of intimate partner violence during pregnancy
      (56.1% vs 43.9%; P = .09) between women who did and did not receive counseling.
      CONCLUSION: Counseling regarding psychosocial risk factors during pregnancy may
      positively impact maternal behavior.

PMID- 23159700
TI  - Shapes, scents and sounds: quantifying the full multi-sensory basis of conceptual
      knowledge.
AB  - Contemporary neuroscience theories assume that concepts are formed through
      experience in multiple sensory-motor modalities. Quantifying the contribution of
      each modality to different object categories is critical to understanding the
      structure of the conceptual system and to explaining category-specific knowledge
      deficits. Verbal feature listing is typically used to elicit this information but
      has a number of drawbacks: sensory knowledge often cannot easily be translated
      into verbal features and many features are experienced in multiple modalities.
      Here, we employed a more direct approach in which subjects rated their knowledge
      of objects in each sensory-motor modality separately. Compared with these
      ratings, feature listing over-estimated the importance of visual form and
      functional knowledge and under-estimated the contributions of other sensory
      channels. An item's sensory rating proved to be a better predictor of lexical
      semantic processing speed than the number of features it possessed, suggesting
      that ratings better capture the overall quantity of sensory information
      associated with a concept. Finally, the richer, multi-modal rating data not only
      replicated the sensory-functional distinction between animals and non-living
      things but also revealed novel distinctions between different types of artefact.
      Hierarchical cluster analyses indicated that mechanical devices (e.g., vehicles)
      were distinct from other non-living objects because they had strong sound and
      motion characteristics, making them more similar to animals in this respect.
      Taken together, the ratings align with neuroscience evidence in suggesting that a
      number of distinct sensory processing channels make important contributions to
      object knowledge. Multi-modal ratings for 160 objects are provided as
      supplementary materials.

PMID- 23159701
TI  - Modulation of motor cortex activity when observing rewarding and punishing
      actions.
AB  - Interpreting others' actions is essential for understanding the intentions and
      goals in social interactions. Activity in the motor cortex is evoked when we see
      another person performing actions, which can also be influenced by the intentions
      and context of the observed action. No study has directly explored the influence
      of reward and punishment on motor cortex activity when observing others' actions,
      which is likely to have substantial relevance in different social contexts. In
      this experiment, EEG was recorded while participants watched movie clips of a
      person performing actions that led to a monetary reward, loss or no change for
      the observer. Using the EEG mu rhythm as an index of motor resonance, our results
      demonstrate that observation of rewarding actions produce significantly greater
      motor cortex activity than punishing or neutral actions, with punishing actions
      producing greater activity than neutral ones. In addition, the dynamic change in
      the mu rhythm over sensorimotor cortex is modulated by reward and punishment,
      with punishing actions producing a prolonged suppression. These findings
      demonstrate that the associated reward value of an observed action may be crucial
      in determining the strength of the representation of the action in the observer's
      brain. Consequently, reward and punishment is likely to drive observational
      learning through changes in the action observation network, and may also
      influence how we interpret, understand, engage in and empathize with others'
      actions in social interaction.

PMID- 23159702
TI  - Range of motion exercises in the setting of burn-associated heterotopic
      ossification at the elbow: case series and discussion.

PMID- 23159703
TI  - Blood stream infections (BSI) in severe burn patients--early and late BSI: a 9
      year study.
AB  - Bloodstream infections (BSI) and sepsis are among the most common complications
      occurring in severe burn patients. This study was designed to evaluate changes in
      BSI pathogens over almost a decade in severe burn patients at Rambam Healthcare
      Campus, and BSI occurrence during early and late hospitalization periods.
      Retrospective computerized data was retrieved from all severe burn patients
      hospitalized in our institution during the years 2001-2009. BSI in the first week
      was defined as early BSI, and in the second week and beyond, late BSI. Of 159
      severe burns patients, 74 had at least one BSI episode. Most first BSI episodes
      were diagnosed during the first week of hospitalization. In late BSI, an
      increased prevalence of resistant bacteria (methicillin-resistant Staphylococcus
      aureus [MRSA], carbapenem-resistant Klebsiella pneumoniae [CRKP], imipenem
      resistant Pseudomonas aeruginosa [PSE-IMP]) and Candida spp. were observed.
      However, over the 9-year study period, only CRKP increased significantly. In
      summary, except for the sudden appearance and increase in CRKP (8% increase;
      p=0.045), we did not observe a significant change in the BSI pathogen profile
      over the 9-year period. Nevertheless, over the hospitalization period, there is a
      clear change in the BSI bacteria profile, especially after 4 weeks of
      hospitalization.

PMID- 23159704
TI  - Environmentally enriched rearing environments reduce repetitive perseveration in
      caged mink, but increase spontaneous alternation.
AB  - Studies spanning 15 species (including American mink, Neovison vison) demonstrate
      that within similarly-housed populations, individuals displaying high levels of
      stereotypic behaviour (SB) typically show perseverative responding (e.g. during
      set-shifting, or reversal/extinction learning). Similar correlations in autism
      and schizophrenia suggest this indicates captivity-induced cortico-striatal
      circuit dysfunction. However, this pattern does not prove developmental
      impairment: SB, perseveration and their inter-correlations also occur in normal
      humans. We therefore differentially-reared enriched versus non-enriched mink to
      investigate whether treatments that exacerbate SB correspondingly increase
      perseveration (Study 1). Enriched-rearing did reduce SB and perseverative
      response repetition (in two-choice guessing tasks), while increasing spontaneous
      alternation: a strategy yielding more rewards, and suggesting enhanced
      hippocampal development. This complements previous research demonstrating
      cortical/hippocampal impairments and reduced behavioural flexibility in non
      enriched animals, with implications for research animals and wild animals captive
      raised for reintroduction into nature. Consistent with previous data, highly
      stereotypic subjects repeated guessing task responses most rapidly, suggesting
      disinhibition during repetition. However, unexpectedly, SB and perseveration did
      not co-vary across individuals. We therefore suggest that behavioural changes
      manifest as increased perseveration are important but do not fully explain
      captive animals' SBs, possible reasons including the contributory role of
      differential motivations for underlying source behaviours. Re-analyses of old
      data (Study 2) confirmed that spontaneous alternation is profitable; and
      demonstrated that the precise methods used for quantifying perseveration and SB
      can modify the strength of apparent relationships between them, as can
      statistically controlling for feeding motivation: as predicted, partialling out
      motivational effects increased the variance in SB predicted by perseveration.

PMID- 23159705
TI  - Chicago sky blue 6B, a vesicular glutamate transporters inhibitor, attenuates
      methamphetamine-induced hyperactivity and behavioral sensitization in mice.
AB  - Several lines of evidence demonstrate that glutamatergic system plays an
      important role in drug addiction. The present study was designed to investigate
      the effects of Chicago sky blue 6B (CSB6B), a vesicular glutamate transporters
      (VGLUTs) inhibitor, on methamphetamine (METH)-induced behaviors in mice. Mice
      were induced behavioral sensitization to METH by subcutaneous injection of 1mg/kg
      METH once daily for 7 days and then challenged with 1mg/kg METH in 14th day.
      Intracerebroventricular administration of CSB6B (7.5MUg) 2.5h prior to METH was
      to observe its effects on METH -induced behavioral sensitization. Our results
      showed that the expressions of behavioral sensitization were significantly
      attenuated by intracerebroventricular administration of CSB6B 2.5h prior to METH
      either during the development period or before methamphetamine challenge in mice,
      while CSB6B itself had no effect on locomotor activity. Meanwhile, pretreatment
      of CSB6B also attenuated hyperactivity caused by a single injection of METH in
      mice. These results demonstrated that CSB6B, a VGLUTs inhibitor, attenuated acute
      METH-induced hyperactivity and chronic METH-induced behavioral sensitization,
      which indicated that VGLUTs were involved in the effect of chronic METH-induced
      behavioral sensitization and may be a new target against the addiction of METH.

PMID- 23159707
TI  - Intra-orbitofrontal cortex injection of haloperidol removes the beneficial effect
      of methylphenidate on reversal learning of spontaneously hypertensive rats in an
      attentional set-shifting task.
AB  - Numerous studies suggest that attention-deficit/hyperactivity disorder (ADHD) is
      caused by deficits in catecholaminergic systems. Furthermore, dysfunctions of
      prefrontal cortex can impair inhibitory controls of ADHD patients, resulting in
      their impulsive behaviors. Researchers also find that rats with lesions in the
      orbitofrontal cortex show deficits in the reversal learning of attentional set
      shifting task (ASST), a behavioral test frequently used in human studies to asses
      the inhibition system. However, the role of orbitofrontal dopamine system in the
      mechanism responsible for the dysfunctions of inhibitory controls in ADHD
      patients and animal models remains unknown. In the present study, we manipulated
      orbitofrontal dopamine activities of spontaneously hypertensive rats (SHR), a
      widely used ADHD animal model, through intra-peritoneal injection of
      methylphenidate (MPH) and central infusion of haloperidol, and observed their
      performances in ASST. The results show that juvenile SHRs learned slower than
      Wistar controls in the first and second reversal learnings of ASST. The deficits
      could be removed by intra-peritoneal injections of MPH. Furthermore, central
      infusions of haloperidol in the orbitofrontal cortex blocked the effects of MPH.
      In conclusions, dopamine activity in orbitofrontal cortex might play a crucial
      role in the neural mechanism of reversal learning deficits in this animal model
      of ADHD.

PMID- 23159706
TI  - Inhibition of glucocorticoid receptors ameliorates hypobaric hypoxia induced
      memory impairment in rat.
AB  - Chronic exposure to hypobaric hypoxia (HH) causes neurodegeneration and loss of
      memory. The underlying mechanisms of HH induced memory impairment have been
      attributed to prolonged elevated corticosterone level in hippocampus leading to
      augmented glutamate excitotoxicity, oxidative stress, alteration of
      neurotransmitter level or their receptors and calcium mediated signaling. Whether
      this corticosterone mediated neurodegenerative effect occurs through
      overstimulation of glucocorticoid receptors (GRs) or is independent of the GRs,
      is not known. Four groups of rats were taken and GR blocker mifepristone was
      administered intraperitoneally during exposure to HH from 3rd to 7th days. Our
      results showed a duration dependent transcriptional upregulation of GRs and MRs
      following exposure to HH. Prolonged exposure to HH for 7 days augmented the
      translocation of GRs from cytosol to nucleus. Inhibition of GRs during hypoxic
      exposure improved the hippocampal ATP level and modulated the apoptotic markers
      like p53, Bcl(2) and Bax. Decreased expression of L-type calcium channel and NR1
      subunit of NMDA receptors were also observed following administration of
      mifepristone during hypoxic exposure. Morphological studies following
      mifepristone administration during hypoxic exposure showed decreased number of
      pyknotic cells in hippocampus and decrease in apoptotic and necrotic cells in the
      CA3 region of hippocampus. The study indicates that elevated corticosterone level
      during hypoxic exposure causes neurodegeneration and acts through its binding to
      GRs indicating that inhibition of GRs may provide therapeutic effect in
      ameliorating HH induced memory impairment.

PMID- 23159708
TI  - Implementation and evaluation of an optical fiber system as novel process
      monitoring tool during lyophilization.
AB  - Lyophilization is an important and well-established pharmaceutical drying
      process. Product temperature is the most critical process parameter during
      lyophilization as it impacts both product quality and process efficiency.
      Traditionally, thermocouples (TCs) or resistance temperature detectors (RTDs) and
      recently, manometric temperatures measurements (MTMs) have been used to monitor
      the product temperature. But, all of these techniques have several drawbacks. The
      objective of this study was the implementation and evaluation of an optical fiber
      system as novel process monitoring tool during lyophilization. Therefore,
      temperature profiles of mannitol, sucrose, or trehalose were recorded with
      various prototypes of the optical fiber sensors (OFSs) and compared to data
      obtained with conventional TCs or Pirani/capacitance manometry with respect to
      the endpoint of primary drying. The OFS allowed easy handling and easy center
      bottom positioning. Data obtained with the OFS in contact with product were in
      good agreement with data obtained via TCs or Pirani/capacitance manometry. The
      OFSs showed significantly higher sensitivity, faster response, and better
      resolution compared to TCs. This allowed for the detection of additional
      excipient crystallization events. It was found that force effects on unshielded
      sensors enabled to detect glass transitions. Three-dimensional temperature
      profiles were obtained with an OFS helix configuration. The possible integration
      of a glass fiber with several OFSs in series into the shelf surface enables non
      invasive, automatic loading compatible monitoring of the drying process. In
      conclusion, these advantages turn the novel optical fiber systems into a highly
      attractive process monitoring tool during lyophilization.

PMID- 23159710
TI  - Establishment of a triple co-culture in vitro cell models to study intestinal
      absorption of peptide drugs.
AB  - In vitro cell culture models for studying oral drug absorption during early
      stages of drug development have become a useful tool in drug discovery and
      development, with respect to substance throughput and reproducibility. The aim of
      this study was to establish an in vitro cellular model based on human colon
      carcinoma Caco-2, mucus-producing HT29, and Raji B cells in order to design a
      model that more accurately mimics the small intestinal epithelial layer. Normal
      oriented model was set up by seeding co-cultures of Caco-2 and HT29 cells into
      Transwell filters and maintained under identical conditions following addition of
      Raji B to the basolateral chamber. Inverted model was set up seeding Caco-2 and
      HT29 cells on the basolateral chamber and then transferred in the Transwell
      device with the epithelial cells facing the basolateral chamber following Raji B
      addition to the apical compartment. Morphological differences on size and
      thickness of cell membranes were detected between the models studied by using
      fluorescence microscopy. On the triple co-culture models, cell membranes were
      increasing in size and thickness from the Caco-2 to Caco-2/HT29 and Caco-2/Raji
      B. Also, the nuclei seem to be larger than in the other studied models. Insulin
      permeation was higher on the triple co-culture model when compared to the Caco
      2/HT29 co-culture model. Also, insulin permeation as mediated by nanoparticles
      and insulin solution permeation was higher on the normal oriented Caco
      2/HT29/Raji B model as compared to the inverted model. Overall, our results
      suggest that Caco-2/HT29/Raji B triple co-culture normal oriented cellular model
      may be reliable to obtain a more physiological, functional, and reproducible in
      vitro model of the intestinal barrier to study protein absorption, both in
      solution and when delivered by nanocarriers.

PMID- 23159709
TI  - In situ monitoring of carbamazepine-nicotinamide cocrystal intrinsic dissolution
      behaviour.
AB  - Cocrystals have shown huge potential to improve the dissolution rate and
      absorption of a poorly water soluble drug. However, solution mediated phase
      transformation of cocrystals could greatly reduce the enhancement of its apparent
      solubility and dissolution rate. The aim of this study is to gain a deep
      understanding of the phase transition behaviour of cocrystals during dissolution
      and to investigate the improvement of dissolution rate. Dissolution and
      transformation behaviour of carbamazepine-nicotinamide (CBZ-NIC) cocrystal,
      physical mixture and different forms of carbamazepine: form I (CBZ I), form III
      (CBZ III) and dihydrate (CBZ DH) were studied by different in situ techniques of
      UV imaging and Raman spectroscopy. It has been found that compared with CBZ III
      and I, the rate of intrinsic dissolution rate (IDR) of CBZ-NIC cocrystal
      decreases slowly during dissolution, indicating the rate of crystallisation of
      CBZ DH from the solution is slow. In situ solid-state characterisation has shown
      the evolution of conversion of CBZ-NIC cocrystal and polymorphs to its dihydrate
      form. The study has shown that in situ UV imaging and Raman spectroscopy with a
      complementary technique of SEM can provide an in depth understanding during
      dissolution of cocrystals.

PMID- 23159711
TI  - Development and characterisation of a self-microemulsifying drug delivery systems
      (SMEDDSs) for the vaginal administration of the antiretroviral UC-781.
AB  - UC-781 is highly selective and potent against HIV-1. However, its hydrophobic
      nature (logP 5.1) and lack of aqueous solubility have limited its development as
      a HIV microbicide. Self-microemulsifying drug delivery systems (SMEDDSs) have
      been developed to enhance the water solubility and bioavailability of hydrophobic
      drugs, such as UC781. In this study, we show the development of UC781-loaded
      SMEDDS and their enhanced release of UC781 from hard gelatine capsules, when
      compared to UC781 powder only. The majority of antiretrovirals being evaluated as
      potential HIV microbicides are hydrophobic. Therefore, a SMEDDS formulation
      offers an alternative approach to enhancing the vaginal absorption of these
      microbicidal candidates.

PMID- 23159712
TI  - Mucoadhesive multiparticulate patch for the intrabuccal controlled delivery of
      lidocaine.
AB  - The aim of the present study was to prepare and evaluate patches for the
      controlled release of lidocaine in the oral cavity. Mucoadhesive buccal patches,
      containing 8 mg/cm(2) lidocaine base, were formulated and developed by solvent
      casting method technique, using a number of different bio-adhesive and film
      forming semi-synthetic and synthetic polymers (Carbopol, Poloxamer, different
      type Methocel) and plasticizers (PEG 400, triethyl citrate); the patches were
      evaluated for bioadhesion, in vitro drug release and permeation using a modified
      Franz diffusion cell. A lidocaine/Compritol solid dispersion in the form of
      microspheres, embedded inside the patch, alone or together with free lidocaine,
      was also examined to prolong the drug release. The effects of the composition
      were evaluated considering a number of technological parameters and the release
      of the drug. All the formulations tested offer a variety of drug release
      mechanisms, obtaining a quick or delayed or prolonged anesthetic local activity
      with simple changes of the formulation parameters.

PMID- 23159713
TI  - Myoclonic astatic epilepsy (Doose syndrome) - a lamotrigine responsive epilepsy?
AB  - PURPOSE: Myoclonic astatic epilepsy (MAE, Doose syndrome) is a difficult to treat
      idiopathic generalized epilepsy of early childhood. MAE frequently shows the
      course of an epileptic encephalopathy and may result in permanent cognitive
      impairment. Systematic analyses on clinical effects of different AED combinations
      are still needed. The purpose of our study was to analyze the therapeutic effect
      of adjunctive lamotrigine (LTG) in pharmacoresistant MAE patients. PATIENTS AND
      METHODS: In an exploratory, retrospective study, 10 pharmacoresistant MAE
      patients were included who had been admitted to the Northern German Epilepsy
      Center between 07/2007 and 12/2010 and had been treated with LTG. Documentation
      was performed with the electronic seizure diary Epivista. A total observation
      period of 32 weeks was defined: 8-week 'pre LTG treatment phase' (before starting
      with LTG), 16-week 'titration phase' (starting with very low LTG doses), 8-week
      'follow-up phase'. Seizure frequency, medication and adverse events were
      extracted from the electronic diary and evaluated in each particular patient. The
      individual reduction of seizure frequency per day was defined as primary outcome
      variable. Additionally, a dose-effect-relationship was analyzed for each patient.
      RESULTS: Six out of ten patients were seizure free during the follow-up phase.
      Statistical analysis indicated a significant seizure reduction in seven patients
      at follow-up compared to the pre LTG treatment phase. Seizure frequency did not
      significantly decrease in two patients and increased in one patient. A
      significant relationship between seizure frequency per day and LTG dosage during
      titration and follow-up phase could be demonstrated in nine patients. Group
      statistics using the exact Wilcoxon test revealed a significant reduction in
      seizure frequency (p = 0.049, two-sided). CONCLUSION: Our data provide evidence
      that adjunctive LTG is an eligible therapeutic option for the treatment of
      pharmacoresistant MAE and encourage further prospective studies to verify this
      observation.

PMID- 23159714
TI  - Levetiracetam in children, adolescents and young adults with intractable
      epilepsy: efficacy, tolerability and effect on electroencephalogram--a pilot
      study.
AB  - Levetiracetam has been authorized for use in Israel as an add-on therapy for
      intractable epilepsy since May 2006. The aim of the present study was to document
      its effectiveness for this indication in children, adolescents, and young adults.
      The medical files of 78 patients aged 0.5-39 years (mean, 14.2 years) treated at
      our center for intractable epilepsy were reviewed. All received levetiracetam as
      add-on therapy following a failure to respond to at least 3 anti-epileptic drugs.
      Fifty-two patients (67%) had partial epilepsy and the remainder had primary
      generalized epilepsy. The epilepsy was symptomatic in 57%, cryptogenic in 27%,
      and idiopathic in 15%. Average age at first seizure was 4.1 years. In 45% of
      patients, the number of seizures was reduced by half with levetiracetam
      treatment; 11.5% of the cohort achieved complete remission. There was a
      statistically significant correlation between clinical seizure control and
      improvement in the electroencephalography findings (p = 0.0012). The drug was
      well tolerated, with a retention rate of 69% after one year. The most common
      adverse effects were irritability and impulsiveness, in 26.9% of patients. Severe
      behavioral side effects (psychosis, confusion) were experienced by 6.4%. In
      conclusion, levetiracetam is an effective and tolerable add-on agent for use in
      most epileptic children, adolescents, and young adults who fail to respond to at
      least 3 antiepileptic drugs and should be the treatment of choice in this
      setting. Despite the relatively high rate of behavioral side effects in this
      study, the retention rate at one year was high.

PMID- 23159715
TI  - Epidemiology of dementias and Alzheimer's disease.
AB  - BACKGROUND AND AIMS: Global population aging has been one of the defining
      processes of the twentieth century, with profound economic, political and social
      consequences. It is driving the current epidemic of dementia, both in terms of
      its extent and global distribution. The aim of the study was to summarize recent
      findings relevant to the epidemiological knowledge of dementia and Alzheimer's
      disease (AD). METHODS: A narrative mini-review of the literature relevant to the
      epidemiology of dementia and AD is presented, summarizing important findings and
      analyzing their implications. RESULTS: It was estimated that in 2010 there were
      36.5 million people living with dementia, with 7.7 million new cases yearly and a
      new case of dementia every 4 sec. The number of persons living with dementia will
      nearly double every 20 years. Most of these persons will be living in low- and
      middle-income countries (LMIC). CONCLUSIONS: There are a substantial number of
      people with dementia worldwide and these numbers will continue to increase mainly
      in LMIC, producing a wide range of impacts. It is important to make dementia a
      national public health and social care priority worldwide. Recent reviews and
      meta-analyses have failed to clearly identify a singular causal or preventive
      pathway for AD that seems to be a multicausal, heterogeneous and age-related
      condition.

PMID- 23159716
TI  - Influence of the core circadian gene "Clock" on obesity and leptin resistance in
      mice.
AB  - Alterations in metabolism could be due to cell-autonomous effects associated with
      altered expression of Clock in central nervous system feeding centers and/or
      peripheral tissues involved in metabolism. Clock mutant mice are hyperphagic and
      obese, which indicates that Clock is related to obesity. In the present study, we
      used intracerebroventricular injection of recombinant adenoviral vector harboring
      Clock genes to explore the role of Clock on diet induced obesity and the
      mechanisms involved in leptin resistance and leptin signaling in mice. The
      results demonstrated that expression of Clock in the arcuate nucleus of diet
      induced obesity mice was down-regulated. The recombinant adenoviral vector
      harboring Clock genes could reduce obesity indexes of diet induced obesity mice
      including body weight, BMI and total fat mass, attenuate hyperleptinemia,
      increase leptin sensitivity and decrease accumulated suppressor of cytokine
      signaling-3 in the arcuate nucleus. These results indicate that Clock plays an
      important role on obesity, which may be involved in leptin resistance and
      regulation of suppressor of cytokine signaling-3 in arcuate nucleus.

PMID- 23159717
TI  - Regulation of tau proteolysis by phosphatases.
AB  - One pathological hallmark of Alzheimer's disease is the accumulation of highly
      phosphorylated tau. Since tau phosphorylation inhibits its proteolysis, we
      examined the impact of endogenous phosphatase activities on tau proteolysis by
      homogenization of cultured cells and 3xTg-AD mouse brain followed by incubation
      with or without phosphatase inhibitors. Incubation without phosphatase inhibitors
      significantly increased tau immunoreactivity against antibody C3 (which reacts
      with tau truncated at D421), and increased the generation of tau breakdown
      products. These changes were augmented by lithium treatment and inhibited by
      constitutively active GSK3beta. These findings underscore that tau proteolysis is
      regulated by a balance of kinase and phosphatase activities.

PMID- 23159718
TI  - The Akt-FoxO3a-manganese superoxide dismutase pathway is involved in the
      regulation of oxidative stress in diabetic nephropathy.
AB  - Oxidative stress has been shown to play an important role in the development and
      progression of diabetic nephropathy, and the formation of reactive oxygen species
      (ROS) is a direct consequence of hyperglycaemia. We hypothesized that
      hyperglycaemia-induced ROS can activate the transforming growth factor-beta1 (TGF
      beta1)-phosphoinositide 3-kinase (PI3K)-Akt-FoxO3a signalling pathway, negatively
      regulating expression of manganese superoxide dismutase (MnSOD), which promotes
      excessive ROS generation and accelerates the pathological process of diabetic
      nephropathy. In vitro, in rat mesangial cells, high glucose (30 mmol l(-1)), but
      not equimolar mannitol, stimulated ROS production, upregulated the levels of TGF
      beta1, increased the phosphorylated Akt/total Akt and phosphorylated FoxO3a/total
      FoxO3a protein ratios, altered the subcellular localization of FoxO3a and reduced
      the levels of MnSOD expression. These high-glucose-induced changes further
      promoted the generation of ROS. In vivo, in db/db mice treated with an inhibitor
      of TGF-beta1 (SB431542) or PI3K (LY294002), the levels of phosphorylated Akt and
      phosphorylated FoxO3a in the kidney cortices were decreased, the level of MnSOD
      expression was increased and the level of the lipid peroxidation end-product,
      malondialdehyde, was reduced. We conclude that overproduction of ROS induced by a
      high glucose concentration decreases the expression of MnSOD via the PI3K-Akt
      FoxO3a pathway and further aggravates oxidative stress in diabetic nephropathy.

PMID- 23159719
TI  - T1rho MRI relaxation in knee OA subjects with varying sizes of cartilage lesions.
AB  - BACKGROUND: The purpose of this investigation is to evaluate the T(1rho)
      relaxation times of articular cartilage surrounding focal defects in the
      tibiofemoral joint. METHODS: Quantitative cartilage assessment was performed
      using 3T MRI with T(1rho) mapping in 19 healthy individuals and 44 OA patients.
      Sagittal T2-weighted fast spin echo (FSE) images were acquired for lesion
      assessment. Differences were determined using analysis of variance (ANOVA).
      RESULTS: Cartilage lesions were found in 37% of controls, and 93% of OA patients.
      Meniscal tears were found in 16% of controls and 57% of OA patients. We observed
      no difference in T(1rho) relaxation times when comparing cartilage immediately
      surrounding a focal defect, and the remaining cartilage within that compartment.
      The medial femoral condyle (MFC) had the highest incidence of cartilage defects.
      MFC and medial meniscus posterior horn T(1rho) were higher in subjects having
      multiple focal lesions (p = 0.048, pb 0.001 respectively) and extensive full
      thickness lesions (p = 0.009, pb 0.001 respectively) compared to subjects with no
      MFC defects. Significant elevations in T(1rho) of the adjacent compartment
      (medial tibia) and medial meniscus were observed in subjects with MFC lesions.
      CONCLUSION: Increased relaxation times in the involved compartment as well as the
      adjacent compartment and associated meniscus underscore the interdependence of
      these structures at bearing load. However, no differences in cartilage
      composition immediately surrounding a defect were noted. Finally, an association
      was observed between cartilage defects and meniscal damage in advanced disease.
      CLINICAL RELEVANCE: Cartilage defects were not associated with degeneration in
      the immediately adjacent cartilage.

PMID- 23159720
TI  - Five year survival analysis of an oxidised zirconium total knee arthroplasty.
AB  - BACKGROUND: Zirconium total knee arthroplasties theoretically have a low
      incidence of failure as they are low friction, hard wearing and hypoallergenic.
      We report the five year survival of 213 Profix zirconium total knee
      arthroplasties with a conforming all polyethylene tibial component. METHODS: Data
      was collected prospectively and multiple strict end points were used. SF12 and
      WOMAC scores were recorded pre-operatively, at three months, at twelve months, at
      3 years and at 5 years. RESULTS: Eight patients died and six were "lost to follow
      up". The remaining 199 knees were followed up for five years. The mean WOMAC
      score improved from 56 to 35 and the mean SF12 physical component score improved
      from 28 to 34. The five year survival for failure due to implant related reasons
      was 99.5% (95% CI 97.4-100). This was due to one tibial component becoming loose
      aseptically in year zero. CONCLUSIONS: Our results demonstrate that the Profix
      zirconium total knee arthroplasty has a low medium term failure rate comparable
      to the best implants. Further research is needed to establish if the beneficial
      properties of zirconium improve long term implant survival.

PMID- 23159721
TI  - The immediate effects of open kinetic chain knee extensor exercise at different
      loads on knee anterior laxity in the uninjured.
AB  - BACKGROUND: There is evidence that anterior laxity may be affected by knee
      extensor open kinetic chain (OKC) exercise with responses being load-dependent.
      The aim of this study is to evaluate the immediate and short-term changes in
      passive knee anterior laxity following a single session of OKC knee extensor
      exercise. METHODS: Thirty two participants were randomly allocated to perform
      either high load (20 sets of 2 repetitions) or low load (2 sets of 20
      repetitions) knee extensor OKC exercise with knee anterior laxity assessed before
      exercise, immediately after exercise and 45 and 90min after exercise with a KT
      2000 arthrometer using a 133N force. RESULTS: A significant effect of time was
      observed on knee laxity (p<0.001). However, a significant interaction of time and
      group was not found (p=0.54) and so the results presented here are for the
      combined (low and high load) group mean+/-standard deviation knee anterior laxity
      (mm) in the exercised leg: 7.2+/-2.2 (baseline), 8.2+/-2.3 (immediate post
      exercise, 14% change from baseline), 8.1+/-2.3 (45min post exercise, 12% change
      from baseline), and 7.7+/-2.2/0.29 (6.9) (90min post exercise, 7% change from
      baseline). CONCLUSION: OKC knee extensor exercise at high loads and low loads
      causes an immediate increase in knee laxity that begins to decrease within 90min.

PMID- 23159722
TI  - Intranasal oxytocin and its rapidly expanding role in psychiatry.

PMID- 23159723
TI  - Neuroendocrine homeostasis after vagus nerve stimulation in rats.
AB  - BACKGROUND: The vagus nerve is important in maintaining HPA axis and sympatho
      adrenal system (SAS) homeostasis, however little is known about the effect of
      vagus nerve stimulation (VNS), as used therapeutically, on these functions.
      Accordingly, the effect of VNS on plasma indices of HPA axis (ACTH,
      corticosterone), and SAS (norepinephrine, epinephrine) function were evaluated in
      rats. METHODS: Male rats, on day-0 (D0), underwent surgeries for implantation of
      catheters into the right jugular vein and programmable (VNP) or non-programmable
      (VND) neurocybernetic devices encircling the left cervical vagus. On D7, after a
      blood sample, the device in VNP rats was programmed to deliver 500 MUs width,
      0.25 mA current pulses at 20 Hz ('on' 30s, 'off' 5 min) followed by timed blood
      samples during the next 90 min. In acute studies, VNS was stopped at 60 min and
      the rats were perfused at 90 min to evaluate neuronal Fos immunoreactivity (Fos
      IR). In chronic studies, the probe remained active. In these rats, the HPA axis
      response to airpuff-startle stressor (D17) and anterior pituitary CRF-receptor
      binding (D26) were evaluated. RESULTS: During acute VNS, plasma indices of HPA
      axis and SAS activity, as well as Fos-IR activation pattern in brain regions
      known to increase after stress, were not different between VND and VNP rats.
      During chronic VNS, stress-induced HPA axis responses exhibited a tendency toward
      faster recovery to baseline in VNP rats. CONCLUSIONS: Therapeutic VNS is not a
      stressor and does not compromise HPA axis or SAS homeostasis. Chronic VNS may
      facilitate development of efficient feedback mechanisms.

PMID- 23159725
TI  - Indicators of positive and negative emotions and emotional contagion in pigs.
AB  - For the welfare of group-housed animals, such as pigs, the emotional state of an
      individual pig is relevant, but also the extent to which pen mates are affected
      by the distress or pleasure of other individuals, i.e. emotional contagion, a
      simple form of empathy. Therefore, indicators of positive and negative emotions
      were investigated in pigs during anticipation and experience of a rewarding
      (access in pairs to a compartment with straw, peat and chocolate raisins) or
      aversive (social isolation combined with negative, unpredictable interventions)
      event. Thereafter the same indicators were investigated in naive pigs during
      anticipation and experience of a rewarding or aversive event by their trained pen
      mates. Positive emotions could be indicated by play, barks and tail movements,
      while negative emotions could be indicated by freezing, defecating, urinating,
      escape attempts, high-pitched vocalizations (screams, squeals or grunt-squeals),
      tail low, ears back and ear movements. Salivary cortisol measurements supported
      these behavioral observations. During anticipation of the aversive event, naive
      pigs tended to show more tail low. During the aversive event, naive pigs tended
      to defecate more, while they played more during the rewarding event. These
      results suggest that pigs might be sensitive to emotional contagion, which could
      have implications for the welfare of group-housed pigs. Pig emotions and the
      process of emotional contagion merit, therefore, further research.

PMID- 23159724
TI  - The effect of unpredictable chronic mild stress on depressive-like behavior and
      on hippocampal A1 and striatal A2A adenosine receptors.
AB  - This study examined the effects of two chronic stress regimens upon depressive
      like behavior, A(1) and A(2A) adenosine receptor binding and immunocontent. Male
      rats were subjected to unpredictable chronic mild stress (UCMS) or to chronic
      restraint stress (CRS) for 40 days. Subsequently, depressive-like behaviors
      (forced swimming and consumption of sucrose) were evaluated, and A(1) adenosine
      or A(2A) adenosine receptors were examined in the hippocampus or striatum,
      respectively. UCMS animals demonstrated depressive-related behaviors (decrease in
      sucrose consumption and increased immobility in the forced swimming test). This
      group also presented increased A(1) adenosine receptor binding and
      immunoreactivity in hippocampus, as well as increased striatal A(2A) adenosine
      receptor binding in the striatum, without alteration in immunoreactivity.
      Conversely, the chronic restraint stress group displayed only an increase in A(1)
      adenosine receptor binding and no alteration in the other parameters evaluated.
      We suggest that the alteration in adenosine receptors, particularly the
      upregulation of striatal A(2A) adenosine receptors following UCMS, could be
      associated with depressive-related behavior.

PMID- 23159726
TI  - Photosystem trap energies and spectrally-dependent energy-storage efficiencies in
      the Chl d-utilizing cyanobacterium, Acaryochloris marina.
AB  - Acaryochloris marina is the only species known to utilize chlorophyll (Chl) d as
      a principal photopigment. The peak absorption wavelength of Chl d is redshifted
      ~40nm in vivo relative to Chl a, enabling this cyanobacterium to perform oxygenic
      phototrophy in niche environments enhanced in far-red light. We present
      measurements of the in vivo energy-storage (E-S) efficiency of photosynthesis in
      A. marina, obtained using pulsed photoacoustics (PA) over a 90-nm range of
      excitation wavelengths in the red and far-red. Together with modeling results,
      these measurements provide the first direct observation of the trap energies of
      PSI and PSII, and also the photosystem-specific contributions to the total E-S
      efficiency. We find the maximum observed efficiency in A. marina (40+/-1% at
      735nm) is higher than in the Chl a cyanobacterium Synechococcus leopoliensis
      (35+/-1% at 690nm). The efficiency at peak absorption wavelength is also higher
      in A. marina (36+/-1% at 710nm vs. 31+/-1% at 670nm). In both species, the trap
      efficiencies are ~40% (PSI) and ~30% (PSII). The PSI trap in A. marina is found
      to lie at 740+/-5nm, in agreement with the value inferred from spectroscopic
      methods. The best fit of the model to the PA data identifies the PSII trap at
      723+/-3nm, supporting the view that the primary electron-donor is Chl d, probably
      at the accessory (Chl(D1)) site. A decrease in efficiency beyond the trap
      wavelength, consistent with uphill energy transfer, is clearly observed and fit
      by the model. These results demonstrate that the E-S efficiency in A. marina is
      not thermodynamically limited, suggesting that oxygenic photosynthesis is viable
      in even redder light environments.

PMID- 23159727
TI  - Characterization of the Synechocystis PCC 6803 Fluorescence Recovery Protein
      involved in photoprotection.
AB  - Under high irradiance, most cyanobacteria induce a photoprotective mechanism that
      decreases the energy arriving at the photosynthetic reaction centers to avoid the
      formation of dangerous species of oxygen. This mechanism which rapidly increases
      the heat dissipation of excess energy at the level of the cyanobacterial antenna,
      the phycobilisomes, is triggered by the photoactivation of the Orange Carotenoid
      Protein (OCP). Under low light conditions, the Fluorescence Recovery Protein
      (FRP) mediates the recovery of the full antenna capacity by accelerating the
      deactivation of the OCP. Several FRP Synechocystis mutants were constructed and
      characterized in terms of the OCP-related photoprotective mechanism. Our results
      demonstrate that Synechocystis FRP starts at Met26 and not at Met1 (according to
      notation in Cyanobase) as was previously suggested. Moreover, changes in the
      genomic region upstream the ATG encoding for Met26 influenced the concentration
      of OCP in cells. A long FRP (beginning at Met1) is synthesized in Synechocystis
      cells when the frp gene is under the control of the psbA2 promoter but it is less
      active than the shorter protein. Overexpression of the short frp gene in
      Synechocystis enabled short FRP isolation from the soluble fraction. However, the
      high concentration of FRP in this mutant inhibited the induction of the
      photoprotective mechanism by decreasing the concentration of the activated OCP.
      Therefore, the amplitude of photoprotection depends on not only OCP concentration
      but also on that of FRP. The synthesis of FRP and OCP must be strictly regulated
      to maintain a low FRP to OCP ratio to allow efficient photoprotection.

PMID- 23159728
TI  - Triclosan exposure alters postembryonic development in a Pacific tree frog
      (Pseudacris regilla) Amphibian Metamorphosis Assay (TREEMA).
AB  - The Amphibian Metamorphosis Assay (AMA), developed for Xenopus laevis, is
      designed to identify chemicals that disrupt thyroid hormone (TH)-mediated
      biological processes. We adapted the AMA for use on an ecologically-relevant
      North American species, the Pacific tree frog (Pseudacris regilla), and applied
      molecular endpoints to evaluate the effects of the antibacterial agent, triclosan
      (TCS). Premetamorphic (Gosner stage 26-28) tadpoles were immersed for 21 days in
      solvent control, 1.5 MUg/L thyroxine (T(4)), 0.3, 3 and 30 MUg/L (nominal) TCS,
      or combined T(4)/TCS treatments. Exposure effects were scored by morphometric
      (developmental stage, wet weight, and body, snout-vent and hindlimb lengths) and
      molecular (mRNA abundance using quantitative real time polymerase chain reaction)
      criteria. T(4) treatment alone accelerated development concomitant with altered
      levels of TH receptors alpha and beta, proliferating cell nuclear antigen, and
      gelatinase B mRNAs in the brain and tail. We observed TCS-induced perturbations
      in all of the molecular and morphological endpoints indicating that TCS exposure
      disrupts coordination of postembryonic tadpole development. Clear alterations in
      molecular endpoints were evident at day 2 whereas the earliest morphological
      effects appeared at day 4 and were most evident at day 21. Although TCS alone (3
      and 30 MUg/L) was protective against tadpole mortality, this protection was lost
      in the presence of T(4). The Pacific tree frog is the most sensitive species
      examined to date displaying disruption of TH-mediated development by a common
      antimicrobial agent.

PMID- 23159729
TI  - Immunotoxic effects of oil sands-derived naphthenic acids to rainbow trout.
AB  - Naphthenic acids are the major organic constituents in waters impacted by oil
      sands. To investigate their immunotoxicity, rainbow trout (Oncorhynchus mykiss)
      were injected with naphthenic acids extracted from aged oil sands tailings water.
      In two experiments, rainbow trout were injected intraperitoneally with 0, 10, or
      100 mg/kg of naphthenic acids, and sampled after 5 or 21 d. Half of the fish from
      the 21 d exposure were co-exposed to inactivated Aeromonas salmonicida (A.s.) to
      induce an immune response. A positive control experiment was conducted using an
      intraperitoneal injection of 100 mg/kg of benzo[a]pyrene, a known immune
      suppressing compound. T-lymphocytes, B-lymphocytes, thrombocytes, and myeloid
      cells were counted in blood and lymphatic tissue using flow cytometry. In the 5d
      exposure, there was a reduction in blood leucocytes and spleen thrombocytes at
      the 100 mg/kg dose. However, at 21 d, leucocyte populations showed no effects of
      exposure with the exception that spleen thrombocyte populations increase at the
      100 mg/kg dose. In the 21 d exposure, B- and T-lymphocytes in blood showed a
      significant Dose * A.s. interaction, indicating stimulated blood cell
      proliferation due to naphthenic acids alone as well as due to A.s. Naphthenic
      acid injections did not result in elevated bile fluorescent metabolites or
      elevated hepatic EROD activity. In contrast to naphthenic acids exposures, as
      similar dose of benzo[a]pyrene caused a significant decrease in B- and T
      lymphocyte absolute counts in blood and relative B-lymphocyte counts in spleen.
      Results suggest that the naphthenic acids may act via a generally toxic mechanism
      rather than by specific toxic effects on immune cells.

PMID- 23159730
TI  - Antibody-mediated neutralization of African swine fever virus: myths and facts.
AB  - Almost all viruses can be neutralized by antibodies. However, there is some
      controversy about antibody-mediated neutralization of African swine fever virus
      (ASFV) with sera from convalescent pigs and about the protective relevance of
      antibodies in experimentally vaccinated pigs. At present, there is no vaccine
      available for this highly lethal and economically relevant virus and all
      classical attempts to generate a vaccine have been unsuccessful. This failure has
      been attributed, in part, to what many authors describe as the absence of
      neutralizing antibodies. The findings of some studies clearly contradict the
      paradigm of the impossibility to neutralize ASFV by means of monoclonal or
      polyclonal antibodies. This review discusses scientific evidence of these types
      of antibodies in convalescent and experimentally immunized animals, the nature of
      their specificity, the neutralization-mediated mechanisms demonstrated, and the
      potential relevance of antibodies in protection.

PMID- 23159732
TI  - The specific interaction of the photosensitizer methylene blue with
      acetylcholinesterase provides a model system for studying the molecular
      consequences of photodynamic therapy.
AB  - The photosensitizer, methylene blue (MB), generates singlet oxygen ((1)O2) that
      irreversibly inhibits Torpedo californica acetylcholinesterase (TcAChE). In the
      dark MB inhibits reversibly, binding being accompanied by a bathochromic shift
      that can be used to show its displacement by other reversible inhibitors binding
      to the catalytic 'anionic' subsite (CAS), the peripheral 'anionic' subsite (PAS),
      or bridging them. Data concerning both reversible and irreversible inhibition are
      here reviewed. MB protects TcAChE from thermal denaturation, and differential
      scanning calorimetry reveals a ~8  degrees C increase in the denaturation
      temperature. The crystal structure of the MB/TcAChE complex reveals a single MB
      stacked against W279 in the PAS, pointing down the gorge towards the CAS. The
      intrinsic fluorescence of the irreversibly inhibited enzyme displays new emission
      bands that can be ascribed to N'-formylkynurenine (NFK); this was indeed
      confirmed using anti-NFK antibodies. Mass spectroscopy revealed that two Trp
      residues, Trp84 in the CAS, and Trp279 in the PAS, were the only Trp residues,
      out of a total of 14, significantly modified by photo-oxidation, both being
      converted to NFK. In the presence of competitive inhibitors that displace MB from
      the gorge, their modification is completely prevented. Thus, photo-oxidative
      damage caused by MB involves targeted release of (1)O2 by the bound
      photosensitizer within the aqueous milieu of the active-site gorge.

PMID- 23159733
TI  - A retrospective study on the incidence and risk factors of severe hypoglycemia in
      primary care.
AB  - AIMS: To investigate the incidence and risk factors of severe hypoglycemia (SH)
      in primary care. SH was defined as hypoglycemia with coma, or the need of glucose
      or glucagon injection. METHODS: We performed a cross-sectional retrospective
      study in patients with diabetes treated in primary care in Germany. We analyzed
      an unselected sample of participants with type 1 (n = 373) and type 2 diabetes (n
      = 4481) who participated in an insurance plan from the health care insurer
      Deutsche BKK. Data of participants with type 1 diabetes are as follows: women, n
      = 155 (42%); age, 49+/-16 years; diabetes duration, 20+13 years; BMI, 28+/-6
      kg/m2; GHb, 7.1+1.5%; GHb<=7%, n = 263 (71%); GHb>=8.5%, n = 48 (13%). Data of
      participants with type 2 diabetes: women, n = 1979 (44%); age, 66+/-10 years;
      diabetes duration, 8+/-7 years; BMI, 30+/-5 kg/m2; GHb, 6.6+/-1.3%; GHb<=7%, n =
      3747 (84%); GHb>=8.5%, n = 360 (8%); insulin therapy, n = 1175 (26%). RESULTS:
      The incidence of SH in type 1 diabetes: 1.3% (CI: 0.4%, 3.1%) per year; type 2
      diabetes with insulin therapy: 0.9% (CI: 0.5%, 1.7%); without insulin therapy:
      0.3% (CI: 0.1%, 0.6%). The event rate was 0.02 SH per patient/year in type 1
      diabetes and 0.01 in type 2 diabetes, respectively. Low BMI, GHb, insulin therapy
      and female gender were associated with an increased risk of SH. CONCLUSIONS: In
      primary care, patients with diabetes can achieve good glycemic control with very
      rare events of SH. Due to low incidence, SH would have been an inappropriate
      parameter to evaluate the outcome quality of diabetes therapy in primary care.

PMID- 23159731
TI  - miRNAs regulate expression and function of extracellular matrix molecules.
AB  - MicroRNAs (miRNAs) are a family of small non-coding RNA molecules that are made
      up of 18-25 nucleotides that function in post-transcriptional gene regulation.
      The expression of miRNAs is highly conserved and essential in regulating many
      cellular processes including formation, maintenance and the remodelling of the
      extracellular matrix (ECM). In this review, we examine different ECM molecules
      and the miRNAs involved in regulating their abundance and how these changes
      influence cell phenotype. For example, miRNAs and their target messenger RNAs
      (mRNAs) are involved in cell adhesion, by regulating the synthesis and turnover
      of key ECM adhesion molecules and their receptors including cadherins, integrins
      and other non-integrin ECM receptors. Other miRNAs regulate the abundance of
      cytokines and growth factors which in turn stimulate cells to synthesize and
      secrete specialized ECMs. For example, miR-125a/b and miR-146a and their
      downstream target mRNAs influence the production of the epidermal growth factor
      family which has a significant impact on the nature of the ECM formed. miRNAs
      affect structural ECM proteins important in the assembly, composition and
      organization of the ECM. Proteins such as collagen, fibronectin, versican, and
      nephronectin are targeted by several miRNAs. miRNAs can also control the
      expression of proteins such as matrix metalloproteinases (MMPs) and tissue
      inhibitor of metalloproteinases (TIMPs), which are involved in ECM remodelling
      and are important for tissue development, cell motility and wound healing. It has
      become clear that many different miRNAs control the balance in ECM composition
      that determines normal tissue function and alterations in the expression of these
      miRNAs can lead to pathological consequences.

PMID- 23159734
TI  - Tandem mass spectrometry approach for the investigation of the steroidal
      metabolism: structure-fragmentation relationship (SFR) in anabolic steroids and
      their metabolites by ESI-MS/MS analysis.
AB  - Electrospray ionization tandem mass spectrometry (ESI-MS/MS) was used to
      investigate the effect of different substitutions introduced during metabolism on
      fragmentation patterns of four anabolic steroids including methyltestosterone,
      methandrostenolone, cis-androsterone and adrenosterone, along with their
      metabolites. Collision-induced dissociation (CID) analysis was performed to
      correlate the major product ions of 19 steroids with structural features. The
      analysis is done to portray metabolic alteration, such as incorporation or
      reduction of double bonds, hydroxylations, and/or oxidation of hydroxyl moieties
      to keto functional group on steroidal skeleton which leads to drastically changed
      product ion spectra from the respective classes of steroids, therefore, making
      them difficult to identify. The comparative ESI-MS/MS study also revealed some
      characteristic peaks to differentiate different steroidal metabolites and can be
      useful for the unambiguous identification of anabolic steroids in biological
      fluid. Moreover, LC-ESI-MS/MS analysis of fermented extract of
      methyltestosterone, obtained by Macrophomina phaseolina was also investigated.

PMID- 23159735
TI  - Insights into negative regulation by the glucocorticoid receptor from genome-wide
      profiling of inflammatory cistromes.
AB  - How the glucocorticoid receptor (GR) activates some genes while potently
      repressing others remains an open question. There are three current models for
      suppression: transrepression via GR tethering to AP-1/NF-kappaB sites, direct GR
      association with inhibitory elements (nGREs), and GR recruitment of the
      corepressor GRIP1. To gain insights into GR suppression, we used genomic analyses
      and genome-wide profiling of GR, p65, and c-Jun in LPS-stimulated macrophages. We
      show that GR mediates both activation and repression at tethered sites, GREs, and
      GRIP1-bound elements, indicating that motif classification is insufficient to
      predict regulatory polarity of GR binding. Interestingly, sites of GR repression
      utilize GRIP1's corepressor function and display reduced histone acetylation.
      Together, these findings suggest that while GR occupancy confers hormone
      responsiveness, the receptor itself may not participate in the regulatory
      effects. Furthermore, transcriptional outcome is not established by sequence but
      is influenced by epigenetic regulators, context, and other unrecognized
      regulatory determinants.

PMID- 23159736
TI  - The auto-generated fragment of the Usp1 deubiquitylase is a physiological
      substrate of the N-end rule pathway.
AB  - Deamidation of N-terminal Gln by the Ntaq1 Nt(Q)-amidase is a part of the Arg/N
      end rule pathway, a ubiquitin-dependent proteolytic system. Here we identify Gln
      Usp1(Ct), the C-terminal fragment of the autocleaved Usp1 deubiquitylase, as the
      first physiological Arg/N-end rule substrate that is targeted for degradation
      through deamidation of N-terminal Gln. Usp1 regulates genomic stability, in part
      through the deubiquitylation of monoubiquitylated PCNA, a DNA polymerase
      processivity factor. The autocleaved Usp1 remains a deubiquitylase because its
      fragments remain associated with Uaf1, an enhancer of Usp1 activity, until the
      Gln-Usp1(Ct) fragment is selectively destroyed by the Arg/N-end rule pathway. We
      also show that metabolic stabilization of Gln-Usp1(Ct) results in a decreased
      monoubiquitylation of PCNA and in a hypersensitivity of cells to ultraviolet
      irradiation. Thus, in addition to its other functions in DNA repair and
      chromosome segregation, the Arg/N-end rule pathway regulates genomic stability
      through the degradation-mediated control of the autocleaved Usp1 deubiquitylase.

PMID- 23159737
TI  - Characterization of the EZH2-MMSET histone methyltransferase regulatory axis in
      cancer.
AB  - Histone methyltransferases (HMTases), as chromatin modifiers, regulate the
      transcriptomic landscape in normal development as well in diseases such as
      cancer. Here, we molecularly order two HMTases, EZH2 and MMSET, that have
      established genetic links to oncogenesis. EZH2, which mediates histone H3K27
      trimethylation and is associated with gene silencing, was shown to be
      coordinately expressed and function upstream of MMSET, which mediates H3K36
      dimethylation and is associated with active transcription. We found that the EZH2
      MMSET HMTase axis is coordinated by a microRNA network and that the oncogenic
      functions of EZH2 require MMSET activity. Together, these results suggest that
      the EZH2-MMSET HMTase axis coordinately functions as a master regulator of
      transcriptional repression, activation, and oncogenesis and may represent an
      attractive therapeutic target in cancer.

PMID- 23159738
TI  - Mediator-regulated transcription through the +1 nucleosome.
AB  - Many genes are regulated at the level of a Pol II that is recruited to a
      nucleosome-free region upstream of the +1 nucleosome. How the Mediator
      coactivator complex, which functions at multiple steps, affects transcription
      through the promoter proximal region, including this nucleosome, remains largely
      unaddressed. We have established a fully defined in vitro assay system to
      delineate mechanisms for Pol II transit across the +1 nucleosome. Our results
      reveal cooperative functions of multiple cofactors, particularly of Mediator and
      elongation factor SII, in transcribing into this nucleosome. This is achieved, in
      part, through an unusual activity of SII that alters the intrinsic catalytic
      properties of promoter-proximal Pol II and, in concert with the Mediator, leads
      to enhancement in transcription of nucleosomal DNA. Our data provide additional
      mechanistic bases for Mediator function after recruitment of Pol II and,
      potentially, for regulation of genes controlled via nucleosome-mediated promoter
      proximal pausing.

PMID- 23159739
TI  - Structural switch of lysyl-tRNA synthetase between translation and transcription.
AB  - Lysyl-tRNA synthetase (LysRS), a component of the translation apparatus, is
      released from the cytoplasmic multi-tRNA synthetase complex (MSC) to activate the
      transcription factor MITF in stimulated mast cells through undefined mechanisms.
      Here we show that Ser207 phosphorylation provokes a new conformer of LysRS that
      inactivates its translational function but activates its transcriptional
      function. The crystal structure of an MSC subcomplex established that LysRS is
      held in the MSC by binding to the N terminus of the scaffold protein p38/AIMP2.
      Phosphorylation-created steric clashes at the LysRS domain interface disrupt its
      binding grooves for p38/AIMP2, releasing LysRS and provoking its nuclear
      translocation. This alteration also exposes the C-terminal domain of LysRS to
      bind to MITF and triggers LysRS-directed production of the second messenger
      Ap(4)A that activates MITF. Thus our results establish that a single
      conformational change triggered by phosphorylation leads to multiple effects
      driving an exclusive switch of LysRS function from translation to transcription.

PMID- 23159741
TI  - Synchrotron X-ray interlaced microbeams suppress paroxysmal oscillations in
      neuronal networks initiating generalized epilepsy.
AB  - Radiotherapy has shown some efficacy for epilepsies but the insufficient
      confinement of the radiation dose to the pathological target reduces its
      indications. Synchrotron-generated X-rays overcome this limitation and allow the
      delivery of focalized radiation doses to discrete brain volumes via interlaced
      arrays of microbeams (IntMRT). Here, we used IntMRT to target brain structures
      involved in seizure generation in a rat model of absence epilepsy (GAERS). We
      addressed the issue of whether and how synchrotron radiotherapeutic treatment
      suppresses epileptic activities in neuronal networks. IntMRT was used to target
      the somatosensory cortex (S1Cx), a region involved in seizure generation in the
      GAERS. The antiepileptic mechanisms were investigated by recording multisite
      local-field potentials and the intracellular activity of irradiated S1Cx
      pyramidal neurons in vivo. MRI and histopathological images displayed precise and
      sharp dose deposition and revealed no impairment of surrounding tissues. Local
      field potentials from behaving animals demonstrated a quasi-total abolition of
      epileptiform activities within the target. The irradiated S1Cx was unable to
      initiate seizures, whereas neighboring non-irradiated cortical and thalamic
      regions could still produce pathological oscillations. In vivo intracellular
      recordings showed that irradiated pyramidal neurons were strongly hyperpolarized
      and displayed a decreased excitability and a reduction of spontaneous synaptic
      activities. These functional alterations explain the suppression of large-scale
      synchronization within irradiated cortical networks. Our work provides the first
      post-irradiation electrophysiological recordings of individual neurons.
      Altogether, our data are a critical step towards understanding how X-ray
      radiation impacts neuronal physiology and epileptogenic processes.

PMID- 23159742
TI  - Exploring the life cycle of mitochondria in neuropsychiatric diseases:
      mitochondrial dynamics and quality control.

PMID- 23159740
TI  - VE-cadherin signaling induces EB3 phosphorylation to suppress microtubule growth
      and assemble adherens junctions.
AB  - Vascular endothelial (VE)-cadherin homophilic adhesion controls endothelial
      barrier permeability through assembly of adherens junctions (AJs). We observed
      that loss of VE-cadherin-mediated adhesion induced the activation of Src and
      phospholipase C (PLC)gamma2, which mediated Ca(2+) release from endoplasmic
      reticulum (ER) stores, resulting in activation of calcineurin (CaN), a Ca(2+)
      dependent phosphatase. Downregulation of CaN activity induced phosphorylation of
      serine 162 in end binding (EB) protein 3. This phospho-switch was required to
      destabilize the EB3 dimer, suppress microtubule (MT) growth, and assemble AJs.
      The phospho-defective S162A EB3 mutant, in contrast, induced MT growth in
      confluent endothelial monolayers and disassembled AJs. Thus, VE-cadherin outside
      in signaling regulates cytosolic Ca(2+) homeostasis and EB3 phosphorylation,
      which are required for assembly of AJs. These results identify a pivotal function
      of VE-cadherin homophilic interaction in modulating endothelial barrier through
      the tuning of MT dynamics.

PMID- 23159743
TI  - Complexity of neutral zones, lumbar stability and subsystem adaptations: probable
      alterations in lumbosacral transitional vertebrae (LSTV) subtypes.
AB  - Physiological and anatomical ranges of movements at lumbar and lumbo-sacral
      motion segments are influenced by passive (bones and ligaments) and active
      (muscles) elements. The movements are visualized in terms of intrinsically
      unopposed (Neutral Zones) or opposed (Transitional Zones) movement zones. These
      two zones constitute the absolute ranges of motion for different regions of the
      spine. Though values of these ranges for flexion, extension, lateral bending and
      axial rotation at different spinal segments may demonstrate similarities across
      matched population, these parameters are most likely to show different values in
      lumbar spines affected with lumbo-sacral transitional vertebrae (LSTV). LSTV is a
      common variation of the lumbo-sacral junction and present well documented
      structural changes at the lower spine and L5/S1 vertebrae. This study attempts to
      (i) delineate and hypothesize relationships between changes in active and passive
      elements, (ii) understand the possibilities of restriction or augmentation in the
      values of these 'zones', and (iii) to predict overall LSTV induced physiological
      lumbar motion changes, in association with these variations.

PMID- 23159744
TI  - Obesity impairs cell-mediated immunity during the second trimester of pregnancy.
AB  - OBJECTIVE: Obese pregnancy is associated with significantly higher rates of
      infection, which can harm both mother and fetus. The objective of this study was
      to determine the impact of obesity on maternal blood immune function. STUDY
      DESIGN: This was a cross-sectional, case control study of 15 obese (Ob) and 15
      lean (Lc) subjects. Immune cell subsets, intracellular and serum cytokine
      production, and lymphocyte proliferation were measured in maternal blood during
      the second trimester of pregnancy. RESULTS: Obese women had a significantly lower
      proportion of CD8+ and NKT cells and a higher proportion of B cells, impaired
      cytokine production when stimulated ex vivo, and impaired ability of lymphocytes
      to proliferate compared with their lean counterparts. CONCLUSION: Obese pregnancy
      is associated with impaired cell-mediated immunity. Because perinatal infections
      can have serious maternal and fetal consequences, it is imperative to better
      understand these mechanistic underpinnings to optimize prevention and devise
      targeted therapy.

PMID- 23159745
TI  - First-trimester metabolomic detection of late-onset preeclampsia.
AB  - OBJECTIVE: We sought to identify first-trimester maternal serum biomarkers for
      the prediction of late-onset preeclampsia (PE) using metabolomic analysis. STUDY
      DESIGN: In a case-control study, nuclear magnetic resonance-based metabolomic
      analysis was performed on first-trimester maternal serum between 11(+0)-13(+6)
      weeks of gestation. There were 30 cases of late-onset PE, i.e., requiring
      delivery >=37 weeks, and 59 unaffected controls. The concentrations of 40
      metabolites were compared between the 2 groups. We also compared 30 early-onset
      cases to the late-onset group. RESULTS: A total of 14 metabolites were
      significantly elevated and 3 significantly reduced in first-trimester serum of
      late-onset PE patients. A complex model consisting of multiple metabolites and
      maternal demographic characteristics had a 76.6% sensitivity at 100% specificity
      for PE detection. A simplified model using fewer predictors yielded 60%
      sensitivity at 96.6% specificity. Strong separation of late- vs early-onset PE
      groups was achieved. CONCLUSION: Significant differences in the first-trimester
      metabolites were noted in women who went on to developed late-onset PE and
      between early- and late-onset PE.

PMID- 23159746
TI  - Antidepressant medication use patterns during pregnancy and pregnancy outcomes:
      an insight.

PMID- 23159747
TI  - Marinicauda pacifica gen. nov., sp. nov., a prosthecate alphaproteobacterium of
      the family Hyphomonadaceae isolated from deep seawater.
AB  - A marine prosthecate bacterium, designated strain P-1 km-3(T), was isolated from
      deep seawater from the Pacific. Cells of strain P-1 km-3(T) were Gram-stain
      negative, aerobic, catalase- and oxidase-positive, dimorphic rods with a single
      polar prostheca or flagellum. The strain hydrolysed gelatin and grew at 6-40 
      degrees C (optimum, 30  degrees C) and with 0.5-12% (w/v) NaCl (optimum, 2%).
      Phylogenetic analysis of the 16S rRNA gene sequences revealed that strain P-1 km
      3(T) belonged to the family Hyphomonadaceae in the class Alphaproteobacteria and
      represented a separate lineage, located between the genera Oceanicaulis and
      Woodsholea. Sequence similarities of strain P-1 km-3(T) with type strains of
      species of the genera Oceanicaulis and Woodsholea were 93.2-93.9%. The
      predominant cellular fatty acids in strain P-1 km-3(T) were C18:1omega7c, C18:0,
      11-methyl C18:1omega7c, C17:0 and C19:0 cyclo omega8c. The major respiratory
      quinone of strain P-1 km-3(T) was Q-10. The polar lipids of strain P-1 km-3(T)
      comprised glucuronopyranosyldiglyceride (GUDG), monoglycosyldiglyceride (MGDG),
      sulfo-quinovosyl diacylglycerol (SQDG), phosphatidylglycerol (PG), an
      unidentified phospholipid (PL) and an unidentified lipid (L). The genomic DNA G+C
      content of strain P-1 km-3(T) was 66.0 mol%. On the basis of the polyphasic data
      presented in this study, strain P-1 km-3(T) is proposed to represent a novel
      species in a new genus, Marinicauda pacifica gen. nov., sp. nov., within the
      family Hyphomonadaceae. The type strain of the type species is P-1 km-3(T) (=KACC
      16526(T)=CGMCC 1.11031(T)).

PMID- 23159748
TI  - Geodermatophilus telluris sp. nov., an actinomycete isolated from Saharan desert
      sand.
AB  - A novel Gram-positive, multiloculated thalli-forming, aerobic, actinobacterial
      strain, CF9/1/1(T), was isolated in 2007 during environmental screening for
      xerophilic fungi in arid desert soil from the Sahara desert, Chad. The isolate
      grew best at a temperature range of 20-35  degrees C and at pH 6.0-8.5 and with 0
      4% (w/v) NaCl, forming black-coloured and irregular colonies on GYM agar.
      Chemotaxonomic and molecular characteristics of the isolate matched those
      described for members of the genus Geodermatophilus. The DNA G+C content of the
      novel strain was 75.4 mol%. The peptidoglycan contained meso-diaminopimelic acid
      as a diagnostic diamino acid. The main phospholipids were diphosphatidylglycerol,
      phosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol, a not yet
      structurally identified aminophospholipid and a small amount of
      phosphatidylglycerol; MK-9(H4) was identified as the dominant menaquinone and
      galactose was a diagnostic sugar. The major cellular fatty acids were branched
      chain saturated acids: iso-C16:0 and iso-C15:0. The 16S rRNA gene sequence of the
      isolate showed 94.6-97.0% sequence similarities with those of five members of the
      genus: Geodermatophilus ruber DSM 45317(T) (94.6%), Geodermatophilus obscurus DSM
      43160(T) (94.8%), Geodermatophilus siccatus DSM 45419(T) (96.2%),
      Geodermatophilus nigrescens DSM 45408(T) (96.7%) and Geodermatophilus arenarius
      DSM 45418(T) (97.0%). Based on the evidence from this polyphasic taxonomic study,
      a novel species, Geodermatophilus telluris sp. nov., is proposed; the type strain
      is CF9/1/1(T) (=DSM 45421(T)=CCUG 62764(T)).

PMID- 23159749
TI  - Aeromonas australiensis sp. nov., isolated from irrigation water.
AB  - A Gram-negative, facultatively anaerobic bacillus, designated strain 266(T), was
      isolated from an irrigation water system in the south-west of Western Australia.
      Analysis of the 16S rRNA gene sequence confirmed that strain 266(T) belonged to
      the genus Aeromonas, with the nearest species being Aeromonas fluvialis (99.6%
      similarity to the type strain, with 6 nucleotide differences) followed by
      Aeromonas veronii and Aeromonas allosaccharophila (both 99.5%). Analysis of gyrB
      and rpoD sequences suggested that strain 266(T) formed a phylogenetic line
      independent of other species in the genus. This was confirmed using the
      concatenated sequences of six housekeeping genes (gyrB, rpoD, recA, dnaJ, gyrA
      and dnaX) that also indicated that A. veronii and A. allosaccharophila were the
      nearest relatives. DNA-DNA reassociation experiments and phenotypic analysis
      further supported the conclusion that strain 266(T) represents a novel species,
      for which the name Aeromonas australiensis sp. nov. is proposed, with type strain
      266(T) (=CECT 8023(T) =LMG 26707(T)). [corrected].

PMID- 23159750
TI  - Desulfotomaculum defluvii sp. nov., a sulfate-reducing bacterium isolated from
      the subsurface environment of a landfill.
AB  - A novel sulfate-reducing, strictly anaerobic and endospore-forming bacterium,
      designated strain A5LFS102(T), was isolated from a subsurface landfill sample.
      The strain was characterized using a polyphasic approach. Optimal growth was
      observed at 37  degrees C and pH 7.5 with sulfate as an electron acceptor.
      Sulfite and thiosulfate were utilized as electron acceptors. The respiratory
      isoprenoid quinone was menaquinone MK-7. 16S rRNA gene sequence analysis assigned
      strain A5LFS102(T) to the genus Desulfotomaculum. Both 16S rRNA and dissimilatory
      sulfate reductase (dsr) genes were compared with those of representative members
      of the genus Desulfotomaculum. Phylogenetic analysis based on 16S rRNA gene
      sequences revealed that strain A5LFS102(T) was closely related to
      Desulfotomaculum aeronauticum DSM 10349(T) (94.6% sequence similarity). The G+C
      content of the DNA was 45.4 mol%. The total cellular fatty acid profile was
      dominated by C16 fatty acids. These phenotypic and genotypic data showed that
      strain A5LFS102(T) should be recognized as representative of a novel species of
      the genus Desulfotomaculum, for which the name Desulfotomaculum defluvii sp. nov.
      is proposed. The type strain is A5LFS102(T) (=DSM 23699(T)=JCM 14036(T)=MTCC
      7767(T)).

PMID- 23159751
TI  - Methylomonas paludis sp. nov., the first acid-tolerant member of the genus
      Methylomonas, from an acidic wetland.
AB  - An aerobic methanotrophic bacterium was isolated from an acidic (pH 3.9) Sphagnum
      peat bog in north-eastern Russia and designated strain MG30(T). Cells of this
      strain were Gram-negative, pale pink-pigmented, non-motile, thick rods that were
      covered by large polysaccharide capsules and contained an intracytoplasmic
      membrane system typical of type I methanotrophs. They possessed a particulate
      methane monooxygenase enzyme (pMMO) and utilized only methane and methanol.
      Carbon was assimilated via the ribulose-monophosphate pathway; nitrogen was fixed
      via an oxygen-sensitive nitrogenase. Strain MG30(T) was able to grow at a pH
      range of 3.8-7.3 (optimum pH 5.8-6.4) and at temperatures between 8 and 30 
      degrees C (optimum 20-25  degrees C). The major cellular fatty acids were
      C16:1omega5t, C16:1omega8c, C16:1omega7c and C14:0; the DNA G+C content was 48.5
      mol%. The isolate belongs to the family Methylococcaceae of the class
      Gammaproteobacteria and displayed 94.7-96.9% 16S rRNA gene sequence similarity to
      members of the genus Methylomonas. However, strain MG30(T) differed from all
      taxonomically characterized members of this genus by the absence of motility, the
      ability to grow in acidic conditions and low DNA G+C content. Therefore, we
      propose to classify this strain as representing a novel, acid-tolerant species of
      the genus Methylomonas, Methylomonas paludis sp. nov. Strain MG30(T) (=DSM
      24973(T)=VKM B-2745(T)) is the type strain.

PMID- 23159752
TI  - Hoeflea suaedae sp. nov., an endophytic bacterium isolated from the root of the
      halophyte Suaeda maritima.
AB  - A Gram-negative, aerobic, short rod-shaped bacterium, designated strain
      YC6898(T), was isolated from the surface-sterilized root of a halophyte (Suaeda
      maritima) inhabiting tidal flat of Namhae Island, Korea. Strain YC6898(T) grew
      optimally at 30-37  degrees C and pH 6.5-7.5. The strain inhibited mycelial
      growth of Pythium ultimum and Phytophthora capsici. Phylogenetic analyses based
      on 16S rRNA gene sequences indicated that strain YC6898(T) belongs to the genus
      Hoeflea in the family Phyllobacteriaceae. Its closest relatives were Hoeflea
      alexandrii AM1V30(T) (96.7% 16S rRNA gene sequence similarity), Hoeflea anabaenae
      WH2K(T) (95.7%), Hoeflea phototrophica DFL-43(T) (95.5%) and Hoeflea marina LMG
      128(T) (94.8%). Strain YC6898(T) contained Q-10 as the major ubiquinone. The
      major fatty acids of strain YC6898(T) were C18:1omega7c (61.1%), C16:0 (11.9%),
      11-methyl C18:1omega7c (9.6%) and C19:0 cyclo omega8c (8.0%). The polar lipids
      were phosphatidylcholine, phosphatidylethanolamine,
      phosphatidylmonomethylethanolamine, phosphatidylglycerol, unknown lipids and an
      unknown glycolipid. The total genomic DNA G+C content was 53.7 mol%. On the basis
      of phenotypic, chemotaxonomic and phylogenetic analysis, strain YC6898(T)
      represents a novel species of the genus Hoeflea, for which the name Hoeflea
      suaedae sp. nov. is proposed. The type strain is YC6898(T) (=KACC 14911(T)=NBRC
      107700(T)).

PMID- 23159753
TI  - Mycobacterium parakoreense sp. nov., a slowly growing non-chromogenic species
      related to Mycobacterium koreense, isolated from a human clinical specimen.
AB  - A previously undescribed, slowly growing, non-chromogenic Mycobacterium strain
      (299(T)) was isolated from the sputum sample of a patient with a symptomatic
      pulmonary infection. Phenotypically, strain 299(T) was generally similar to
      Mycobacterium koreense DSM 45576(T) and Mycobacterium triviale ATCC 23292(T). The
      16S rRNA gene sequence of strain 299(T) was similar to that of M. koreense DSM
      45576(T) (GenBank accession no. AY734996, 99.5% similarity); however, it differed
      substantially from that of M. triviale ATCC 23292(T) (X88924, 98.2%).
      Phylogenetic analysis based on 16S rRNA gene sequences showed that strain 299(T)
      clustered together with M. koreense DSM 45576(T) and M. triviale ATCC 23292(T),
      supported by high bootstrapping values (99%). Unique mycolic acid profiles and
      phylogenetic analysis based on two different chronometer molecules, the hsp65 and
      rpoB genes, strongly supported the taxonomic status of this strain as
      representing a distinct species. These data support the conclusion that strain
      299(T) represents a novel mycobacterial species, for which the name Mycobacterium
      parakoreense sp. nov. is proposed. The type strain is 299(T) (=DSM 45575(T)=KCTC
      19818(T)).

PMID- 23159754
TI  - Kazachstania rupicola sp. nov., a yeast species isolated from water tanks of a
      bromeliad in Brazil.
AB  - Two isolates of a novel yeast species were obtained from water tanks
      (phytotelmata) of the bromeliad Vriesea minarum collected in a tableland ('campo
      rupestre') ecosystem in Brazil. The sequences of the D1/D2 domains of the large
      subunit rRNA gene showed that this species is related to Kazachstania exigua and
      others, from which it differs by 8-10 nucleotide substitutions. The novel species
      Kazachstania rupicola sp. nov. is proposed to accommodate these isolates. The
      type strain is UFMG-BRO-80(T) ( = CBS 12684(T)  = CBMAI 1466(T)).

PMID- 23159755
TI  - Undibacterium terreum sp. nov., isolated from permafrost soil.
AB  - The bacterial strain C3(T) was isolated from permafrost soil in Beijicun, Mohe
      County, Heilongjiang province, China. Cells of strain C3(T) were Gram-stain
      negative rods, 0.3-0.4 um in diameter and 1.0-2.6 um in length. Strain C3(T) was
      strictly aerobic. Growth occurred at 15-37  degrees C but not at 4 or 42  degrees
      C, at pH 5.0-9.0 (optimum pH 6.0-7.0) and in the presence of 0-8 g NaCl l(-1)
      (optimum 0-1 g l(-1)). The analysis of 16S rRNA gene sequences indicated that
      strain C3(T) was phylogenetically related to members of the genus Undibacterium,
      with similarities ranging from 94.7 to 96.5%. Strain C3(T) contained ubiquinone 8
      as the major respiratory quinone. The major cellular fatty acids were summed
      feature 3 (C16:1omega7c/C16:1omega6c), C17:0 cyclo, straight-chain C16:0, C12:0
      and C10:0, unsaturated C18:1omega7c and hydroxylated fatty acids C10:0 3-OH and
      C12:0 2-OH. The polar lipids were mainly phosphatidylethanolamine,
      diphosphatidylglycerol and phosphatidylglycerol. The polyamines were putrescine
      and 2-hydroxyputrescine. The DNA G+C content was 57.4 mol% (determined from Tm).
      Based on these results, it is concluded that strain C3(T) represents a novel
      species of the genus Undibacterium, for which the name Undibacterium terreum sp.
      nov. is proposed, with C3(T) (=CGMCC 1.10998(T)=NBRC 108789(T)) representing the
      type strain.

PMID- 23159756
TI  - Lonsdalea quercina subsp. populi subsp. nov., isolated from bark canker of poplar
      trees.
AB  - Seven Gram-negative bacterial strains were isolated from oozing bark canker of
      poplar (Populus * euramericana) trees in Hungary. They showed high (>98.3%) 16S
      rRNA gene sequence similarity to Lonsdalea quercina; however, they differed from
      this species in several phenotypic characteristics. Multilocus sequence analysis
      based on three housekeeping genes (gyrB, atpD and infB) revealed, and DNA-DNA
      hybridization analysis confirmed, that this group of bacterial strains forms a
      distinct lineage within the species Lonsdalea quercina. A detailed study of
      phenotypic and physiological characteristics confirmed the separation of isolates
      from poplars from other subspecies of L. quercina; therefore, a novel subspecies,
      Lonsdalea quercina subsp. populi, type strain NY060(T) (=DSM 25466(T)=NCAIM B
      02483(T)), is proposed.

PMID- 23159757
TI  - Blastopirellula cremea sp. nov., isolated from a dead ark clam.
AB  - Strain LHWP2(T), a novel, aerobic, budding, motile and ovoid bacterium belonging
      to the phylum Planctomycetes, was isolated from a dead ark clam (Scapharca
      broughtonii) from the south coast of Korea. Strain LHWP2(T) grew optimally at 30 
      degrees C, in the presence of 4% (w/v) NaCl, and at pH 7. The predominant
      cellular fatty acids were C16:0, C18:1omega7c and/or C18:1omega6c (summed feature
      8) and C18:1omega9c. The major isoprenoid quinone was menaquinone-6 (MK-6). The
      dominant polar lipid was identified as phosphatidylglycerol. Phylogenetic
      analysis based on 16S rRNA gene sequences indicated that the novel strain was
      most closely related to Blastopirellula marina DSM 3645(T), with a 16S rRNA gene
      sequence similarity of 94.1%. The genomic DNA G+C content of strain LHWP2(T) was
      49.5 mol%. Strain LHWP2(T) was distinguished from B. marina DSM 3645(T) based on
      its optimum salinity, acid production from substrates, assimilation of substrates
      and DNA G+C content. Overall, these phenotypic, genotypic and phylogenetic data
      suggest that strain LHWP2(T) should be classified as a novel species belonging to
      the genus Blastopirellula, for which the name Blastopirellula cremea sp. nov. is
      proposed. The type strain is LHWP2(T) (=KACC 15559(T)=JCM 17758(T)).

PMID- 23159758
TI  - Muricauda zhangzhouensis sp. nov., isolated from mangrove sediment.
AB  - A Gram-staining-negative, rod-shaped and non-motile bacterial strain, designated
      12C25(T), was isolated from the crude-oil-degrading bacterial consortium enriched
      from mangrove sediment collected in Fujian Province, China. Optimal growth was
      observed at 25-28  degrees C, at pH 7.0 and in the presence of 2% (w/v) NaCl + 2%
      (w/v) KCl. Comparative 16S rRNA gene sequence analysis demonstrated that strain
      12C25(T) shared the highest sequence similarity with members of the genus
      Muricauda (97.7-93.9%), exhibiting 97.7% sequence similarity and 33.7 +/- 4% DNA
      DNA relatedness to Muricauda aquimarina SW-63(T). The DNA G+C content of strain
      12C25(T) was 39.9 mol%. The dominant fatty acids were iso-C15:1 G, iso-C17:0 3
      OH, iso-C15:0, C18:0 and iso-C15:0 3-OH, and menaquinone with six isoprene units
      (MK-6) was the only respiratory quinone. On the basis of phenotypic data and
      phylogenetic inference, the novel strain belongs to the genus Muricauda, but can
      readily be distinguished from known species of this genus
      http://dx.doi.org/10.1601/nm.8170 and thus represents a novel species of the
      genus Muricauda. The name Muricauda zhangzhouensis sp. nov. is proposed and the
      type strain is 12C25(T) (=CGMCC 1.11028(T)=MCCC 1F01096(T)=DSM 25030(T)).

PMID- 23159759
TI  - Wettability contrasts between fresh and weathered diesel fuels.
AB  - The remediation of non-aqueous phase liquid (NAPL) contaminated sites is impeded
      due to subsurface complexities, including wettability. Wettability quantifies
      which of two immiscible fluids preferentially coats a solid. At most contaminated
      sites water-wetting conditions are typically assumed despite mounting evidence
      that this is not always the case. In this study, wettability was examined for two
      NAPL samples of contrasting origin: a fresh and a field sample. Wettability was
      assessed through (i) cyclical, 'cumulative elapsed contact time' intrinsic
      contact angle measurements, (ii) interface jar tests, and (iii) cyclical, pseudo
      static capillary pressure-saturation curves. The work as a whole demonstrated
      that while the fresh diesel sample was consistently water-wet, the field diesel
      sample exhibited repeatable cycles of wettability reversal between water drainage
      and imbibition. And while wettability hysteresis increased with contact time for
      the field diesel, the occurrence of wettability reversal at each change of
      saturation direction was independent of contact time. Such behavior is not easily
      assessed by standard wettability indices. Moreover, it contrasts with the
      permanent wettability alteration observed for complex organics (e.g., coal tar)
      observed in most studies. It is hypothesized that the cyclical wettability
      reversal is related to cyclical changes in intermediate pore wettability due to
      sorption of surface active compounds (causing NAPL-wetting imbibition) and
      rupturing of the soil grain water film (causing water-wet drainage). The
      wettability differences between the two NAPLs may be due to additives (i.e., a
      surfactant) in the original formulation and/or byproducts from subsurface
      weathering. These results support better characterization of site-specific
      wettability, improved model development and more realistic site conceptual models
      for improved remediation efforts.

PMID- 23159760
TI  - Multispecies hydrodynamic dispersion under high concentration gradients.
AB  - Recent research suggests that when high concentration gradients (HCG) are
      present, resulting sharp density differences can cause the dispersive flux
      relationship to deviate from its classical Fickian form. This paper presents
      stable, upward, miscible displacement experiments conducted in two different
      types of porous media for a wide range of concentration differences between
      resident and displacing fluids. The considered groundwater velocities ranged from
      advection-dominated transport to velocities where the contribution of molecular
      diffusion is important, with the corresponding Peclet numbers ranging from 0.2 to
      320. In addition to single component displacing fluids, mixtures consisting of
      multiple solutes were considered. The results of this study provide further
      evidence that classical Fick's law over-estimates the dispersion coefficient
      under HCG conditions. The decrease in the apparent dispersion coefficient is
      shown to be a nonlinear function of both concentration difference and groundwater
      velocity. This observation is attributed to gravitational effects at the sub
      continuum scale which are not directly accounted for in classical variable
      density advection/dispersion models. Mixture experiments showed that the
      dispersive behaviors of individual components in a groundwater contaminant
      mixture are coupled.

PMID- 23159761
TI  - Determining the frequency, depth and velocity of preferential flow by high
      frequency soil moisture monitoring.
AB  - Preferential flow in agricultural soils has been demonstrated to result in
      agrochemical mobilisation to shallow ground water. Land managers and
      environmental regulators need simple cost effective techniques for identifying
      soil - land use combinations in which preferential flow occurs. Existing
      techniques for identifying preferential flow have a range of limitations
      including; often being destructive, non in situ, small sampling volumes, or are
      subject to artificial boundary conditions. This study demonstrated that high
      frequency soil moisture monitoring using a multi-sensory capacitance probe
      mounted within a vertically rammed access tube, was able to determine the
      occurrence, depth, and wetting front velocity of preferential flow events
      following rainfall. Occurrence of preferential flow was not related to either
      rainfall intensity or rainfall amount, rather preferential flow occurred when
      antecedent soil moisture content was below 226 mm soil moisture storage (0-70
      cm). Results indicate that high temporal frequency soil moisture monitoring may
      be used to identify soil type - land use combinations in which the presence of
      preferential flow increases the risk of shallow groundwater contamination by
      rapid transport of agrochemicals through the soil profile. However use of high
      frequency based soil moisture monitoring to determine agrochemical mobilisation
      risk may be limited by, inability to determine the volume of preferential flow,
      difficulty observing macropore flow at high antecedent soil moisture content, and
      creation of artificial voids during installation of access tubes in stony soils.

PMID- 23159762
TI  - Effect of dissolved calcium on the removal of bacteriophage PRD1 during soil
      passage: the role of double-layer interactions.
AB  - The objective of this work was to investigate and obtain quantitative relations
      for the effects of Ca(2+) concentration on virus removal in saturated soil and to
      compare the experimental findings with predictions of the DLVO theory. In order
      to do so, a systematic study was performed with a range of calcium concentrations
      corresponding to natural field conditions. Experiments were conducted in a 50-cm
      column with clean quartz sand under saturated conditions. Inflow solutions were
      prepared by adding CaCl(2,) NaCl and NaHCO(3) to de-ionized water. Values of pH
      and ionic strength were fixed at 7 and 10mM, respectively. Bacteriophage PRD1 was
      used as a conservative model virus for virus removal. The samples were assayed
      using the plaque forming technique. Attachment, detachment and inactivation rate
      coefficients were determined from fitting breakthrough curves. Attachment rate
      coefficients were found to increase with increasing calcium concentration.
      Results were used to calculate sticking efficiency, for which an empirical
      formula as a function of Ca(2+) was developed. Numerical solutions of the Poisson
      Boltzmann equation were obtained to evaluate the effect of Ca(2+) on the double
      layer interactions between quartz and PRD1. Based on these results, the DLVO
      interaction energies were calculated. It turned out that the experimental
      findings cannot be explained with the distance profiles of the DLVO interaction.
      The discrepancy between theory and experiment can be attributed to
      underestimation of the van der Waals interactions, chemisorption of Ca(2+) onto
      the surfaces, or by factors affecting the double-layer interactions, which are
      not included in the Poisson-Boltzmann equation. When abruptly changing from
      inflow solution containing Ca(2+) to a Ca(2+)-free solution, pronounced
      mobilization of viruses was observed. This indicates virus removal is not
      irreversible and that chemical perturbations of the groundwater can cause a burst
      of released viruses.

PMID- 23159763
TI  - The behavior of effective rate constants for bimolecular reactions in an
      asymptotic transport regime.
AB  - Previous research has shown that rate constants measured in batch tests (kappa)
      may over-predict the amount of product formation when used in continuum models,
      and that these rate constants are often much greater than effective ones
      (kappa(eff)) determined from upscaling studies. However, there is evidence that
      mixing is more important than the rate constants when using upscaled models. We
      use a numerical two-dimensional pore-scale porous medium with an approach similar
      to an experimental column test, and focus on the scenario of the displacement and
      mixing of two solutions with irreversible bimolecular reactions. Break-through
      curves of multiple cross-sectional averaged concentrations are analyzed for
      conservative and reactive transport, as well as the segregation of reactant
      species along the cross-sections. We compute effective parameters for the
      continuum scale in order to better understand the impact of using intrinsic rate
      constants in upscaled models. For a range of Damkohler numbers (Da), we compute
      effective reaction rate parameters and a reaction effectiveness factor; the
      latter is described by an empirical formula that depends on the Damkohler number
      and captures the upscaled system behavior. Our pore-scale results also confirm
      the segregation concept advanced by Kapoor et al. (1997). We find that for Da>1,
      kappa(eff)<<kappa, and yet the relative difference in total mass transformation
      between the pore-scale simulation and what is predicted by the upscaled continuum
      model using kappa is about 10%. The explanation for this paradox is that the
      early transition of the regime from rate-limited to mixing-limited results in a
      model that is relatively insensitive to the rate constant because mixing controls
      the availability of reactants. Thus, the reaction-rate parameter used in the
      model has limited influence on the rate of product computed.

PMID- 23159765
TI  - Male breast cancers behave differently in elderly patients.
AB  - OBJECTIVE: The aim of this study was to evaluate tumor characteristics,
      management and survival in elderly male breast cancer patients in comparison with
      younger men. METHODS: We reviewed medical records of 99 male breast cancer
      patients between 1972 and 2011. The median age of the patients was 64.5 years.
      Patient characteristics including clinicopathologic factors, treatment
      modalities, survival and prognostic factors were evaluated. Patients were
      subdivided into two groups according to their age (young, <65 years; old, >= 65
      years) and compared based on these factors. RESULTS: Elderly male breast cancer
      patients had larger tumors in more advanced stages at the time of diagnosis
      compared with younger patients. In spite of the larger tumors at presentation,
      older patients had tumors with more favorable biological characteristics, such as
      higher ratio of estrogen and progesterone receptor expression. Ten-year cancer
      specific survival for older patients was 49.2% compared with 55.8% in younger men
      (P = 0.8). Prognostic factors influencing overall survival in univariate analysis
      were: the presence of metastatic axillary lymph nodes (P = 0.0001), T stage (P =
      0.001) and age >= 65 years. Multivariate analysis indicated T stage (P = 0.008)
      and N stage (P = 0.038) as the significant negative prognostic factors for
      overall survival. Although surgery, radiotherapy and hormone therapy were equally
      utilized in old and young patients, old patients were less likely to receive
      adjuvant chemotherapy. CONCLUSIONS: Our study demonstrated the differences in the
      clinical and biological characteristics of male breast cancer according to the
      age of the patients.

PMID- 23159764
TI  - Electrical signatures of ethanol-liquid mixtures: implications for monitoring
      biofuels migration in the subsurface.
AB  - Ethanol (EtOH), an emerging contaminant with potential direct and indirect
      environmental effects, poses threats to water supplies when spilled in large
      volumes. A series of experiments was directed at understanding the electrical
      geophysical signatures arising from groundwater contamination by ethanol.
      Conductivity measurements were performed at the laboratory scale on EtOH-water
      mixtures (0 to 0.97 v/v EtOH) and EtOH-salt solution mixtures (0 to 0.99 v/v
      EtOH) with and without a sand matrix using a conductivity probe and a four
      electrode electrical measurement over the low frequency range (1-1000 Hz). A
      Lichtenecker-Rother (L-R) type mixing model was used to simulate electrical
      conductivity as a function of EtOH concentration in the mixture. For all three
      experimental treatments increasing EtOH concentration resulted in a decrease in
      measured conductivity magnitude (|sigma|). The applied L-R model fitted the
      experimental data at concentration <=0.4v/v EtOH, presumably due to predominant
      and symmetric intermolecular (EtOH-water) interaction in the mixture. The
      deviation of the experimental |sigma| data from the model prediction at higher
      EtOH concentrations may be associated with hydrophobic effects of EtOH-EtOH
      interactions in the mixture. The |sigma| data presumably reflected changes in
      relative strength of the three types of interactions (water-water, EtOH-water,
      and EtOH-EtOH) occurring simultaneously in EtOH-water mixtures as the ratio of
      EtOH to water changed. No evidence of measurable polarization effects at the EtOH
      water and EtOH-water-mineral interfaces over the investigated frequency range was
      found. Our results indicate the potential for using electrical measurements to
      characterize and monitor EtOH spills in the subsurface.

PMID- 23159766
TI  - A preoperative prognostic model predicting recurrence-free survival for patients
      with kidney cancer.
AB  - OBJECTIVE: To develop a preoperative prognostic model in order to predict
      recurrence-free survival in patients with nonmetastatic kidney cancer. METHODS: A
      multi-institutional data base of 1889 patients who underwent surgical resection
      between 1987 and 2007 for kidney cancer was retrospectively analyzed.
      Preoperative variables were defined as age, gender, presentation, size, presence
      of radiological lymph nodes and clinical stage. Univariate and multivariate
      analyses of the variables were performed using the Cox proportional hazards
      regression model. A model was developed with preoperative variables as predictors
      of recurrence after nephrectomy. Internal validation was performed by Harrell's
      concordance index. RESULTS: The median follow-up was 23.6 months (1-222 months).
      During the follow-up, 258 patients (13.7%) developed cancer recurrence. The
      median follow-up for patients who did not develop recurrence was 25 months. The
      median time from surgery to recurrence was 13 months. The 5-year freedom from
      recurrence probability was 78.6%. All variables except age were associated with
      freedom from recurrence in multivariate analyses (P < 0.05). Age was marginally
      significant in the univariate analysis. All variables were included in the
      predictive model. The calculated c-index was 0.747. CONCLUSIONS: This
      preoperative model utilizes easy to obtain clinical variables and predicts the
      likelihood of development of recurrent disease in patients with kidney tumors.

PMID- 23159767
TI  - Reply to: "Direct actions of GLP-1 analogues on AMP-activated protein kinase
      activity are distinct from cyclic AMP accumulation".

PMID- 23159768
TI  - Direct actions of GLP-1 analogues on AMP-activated protein kinase activity are
      distinct from cyclic AMP accumulation.

PMID- 23159769
TI  - Early hepatocellular carcinoma - is there such a thing as too early?

PMID- 23159770
TI  - Improved inflammatory activity with peginterferon alfa-2b maintenance therapy in
      non-cirrhotic prior non-responders: a randomized study.
AB  - BACKGROUND & AIMS: Therapeutic options for patients failing hepatitis C
      retreatment are limited. EPIC(3) included a prospective trial assessing long-term
      peginterferon alfa-2b (PegIFNalpha-2b) maintenance therapy in patients with
      METAVIR fibrosis scores (MFS) of F2 or F3 who previously failed hepatitis C
      retreatment. METHODS: Patients with F2/F3 MFS who failed retreatment were
      randomized to PegIFNalpha-2b (0.5 MUg/kg/week, n=270) or observation (n=270) for
      36 months. Blinded liver biopsies obtained before retreatment and after
      maintenance therapy were evaluated using MFS and activity scores, and
      confirmatory testing was performed using FibroTest and ActiTest. RESULTS: In
      total, 348 patients had paired biopsies: 192 patients had missing post-treatment
      biopsies and were considered as having no change in fibrosis/activity scores. In
      total, 16% of patients receiving PegIFNalpha-2b and 11% of observation patients
      had improvement in MFS (p=0.32). More PegIFNalpha-2b than observation patients
      had improvement in activity score (20% vs. 9%; p <0.001). Among patients treated
      for >2.5 years, improvement in MFS or activity score was more common with
      PegIFNalpha-2b than observation (21% vs. 14%, p=0.08 and 26% vs. 10%, p <0.001).
      FibroTest and ActiTest evaluations indicated significant benefit associated with
      PegIFNalpha-2b in terms of reduced fibrosis progression and improved activity
      score. The safety profile of PegIFNalpha-2b was similar to previous studies.
      CONCLUSIONS: PegIFNalpha-2b did not significantly improve MFS estimated by biopsy
      compared with observation; however, activity scores were significantly improved
      and MFS trended toward increased improvement with treatment durations >2.5 years.
      Both FibroTest and ActiTest were significantly improved during maintenance
      therapy.

PMID- 23159771
TI  - Focus.

PMID- 23159772
TI  - Dissecting the divergent effects of interferon-alpha on immune cells: time to
      rethink combination therapy in chronic hepatitis B?

PMID- 23159773
TI  - Cav1.3 and Cav1.2 channels of adrenal chromaffin cells: emerging views on
      cAMP/cGMP-mediated phosphorylation and role in pacemaking.
AB  - Voltage-gated Ca2+ channels (VGCCs) are voltage sensors that convert membrane
      depolarizations into Ca2+ signals. In the chromaffin cells of the adrenal
      medulla, the Ca2+ signals driven by VGCCs regulate catecholamine secretion,
      vesicle retrievals, action potential shape and firing frequency. Among the VGCC
      types expressed in these cells (N-, L-, P/Q-, R- and T-types), the two L-type
      isoforms, Ca(v)1.2 and Ca(v)1.3, control key activities due to their particular
      activation-inactivation gating and high-density of expression in rodents and
      humans. The two isoforms are also effectively modulated by G protein-coupled
      receptor pathways delimited in membrane micro-domains and by the cAMP/PKA and
      NO/cGMP/PKG phosphorylation pathways which induce prominent Ca2+ current changes
      if opposingly regulated. The two L-type isoforms shape the action potential and
      directly participate to vesicle exocytosis and endocytosis. The low-threshold of
      activation and slow rate of inactivation of Ca(v)1.3 confer to this channel the
      unique property of carrying sufficient inward current at subthreshold potentials
      able to activate BK and SK channels which set the resting potential, the action
      potential shape, the cell firing mode and the degree of spike frequency
      adaptation during spontaneous firing or sustained depolarizations. These
      properties help chromaffin cells to optimally adapt when switching from normal to
      stress-mimicking conditions. Here, we will review past and recent findings on
      cAMP- and cGMP-mediated modulations of Ca(v)1.2 and Ca(v)1.3 and the role that
      these channels play in the control of chromaffin cell firing. This article is
      part of a Special Issue entitled: Calcium channels.

PMID- 23159774
TI  - Enhancement of thermal stability of chondroitinase ABC I by site-directed
      mutagenesis: an insight from Ramachandran plot.
AB  - The application of chondroitinase ABC I (cABC I) in damaged nervous tissue is
      believed to prune glycosaminoglycan chains of proteoglycans, thereby facilitates
      axon regeneration. However, the utilization of cABC I as therapeutics is notably
      restricted due to its thermal instability. In the present study, we have explored
      the possibility of thermostabilization of cABC I through release of its
      conformational strain using Ramachandran plot information. In this regard, Gln140
      with non-optimal phi and psi values were replaced with Gly, Ala and Asn. The
      results indicated that Q140G and Q140A mutants were able to improve both activity
      and thermal stability of the enzyme while Q140N variant reduced the enzyme
      activity and destabilized it. Moreover, the two former variants displayed a
      remarkable resistance to trypsin degradation. Structural analysis of all mutants
      showed an increase in intrinsic fluorescence intensity and secondary structure
      content of Q140G and Q140A compared to the wild type which indicated more compact
      structure upon mutation. This investigation demonstrated that relief of
      conformational tension can be considered as a possible approach to increase the
      stability of the protein.

PMID- 23159775
TI  - [Geriatrics and palliative care: some reflections].
AB  - This article attempts to provide a framework for reflection on the relationships
      between 2 close specialties, such as geriatrics and palliative care. In medicine
      today, with the progressive ageing of the population, 80% of deaths occur at a
      very advanced age, and a high percentage of these are potentially likely to
      receive palliative care in their final stages. The reflections offered in this
      presentation are made from a perspective of someone who has always worked in the
      geriatrics field. Throughout this article, some the common points in the historic
      evolution of both specialities are made and discussed. The inter-relationships
      and common ground in other fields may be, their form of understanding medical
      care, clinical objectives, doctrinal bases, the work methodology, or the
      overlapping of some elements of training. Several aspects of where they differ on
      these same points are also discussed. It is concluded with a call for
      collaboration between the specialists of both fields, as well as in the need to
      demand that the health administrations introduce larger palliative teams in all
      hospitals in the country.

PMID- 23159776
TI  - Poly(ADP-ribose) polymerase inhibition prevents reactive oxygen species induced
      inhibition of aldehyde dehydrogenase2 activity.
AB  - Lipid peroxidation plays a critical role in cardiovascular diseases. Aldehydes
      are the major end products of lipid peroxidation and can be metabolized into less
      reactive chemical species by aldehyde dehydrogenase 2 (ALDH2). However, ALDH2
      dehydrogenase activity can be affected by many factors including reactive oxygen
      species. To elucidate how reactive oxygen species inhibit ALDH2 dehydrogenase
      activity, we stimulated human aortic endothelial cells (HAECs) with oxidized low
      density lipoproteins (ox-LDL) and performed a myocardial ischemia-reperfusion
      model. Ox-LDL treatment and ischemia-reperfusion injury inhibited ALDH2
      dehydrogenase activity. Poly(ADP-ribose) polymerase (PARP) was activated by ox
      LDL stimulation and ischemia-reperfusion injury and PARP inhibition partly
      restored ALDH2 dehydrogenase activity in ox-LDL treated HAECs and ischemia
      reperfusion rat hearts. SIRT3 was upregulated by ox-LDL stimulation and ischemia
      reperfusion injury and downregulated by PARP inhibition. Using siRNA to knock
      down SIRT3, we demonstrated that SIRT3 mediated deacetylation decreased ALDH2
      dehydrogenase activity and PARP inhibition partly restored ALDH2 dehydrogenase
      activity through preventing SIRT3 expression and subsequently preserving ALDH2
      acetylation.

PMID- 23159777
TI  - Towards delineation of a developmental alpha-importome in the mammalian male
      germline.
AB  - Nucleocytoplasmic transport mediated by importin proteins is central to many
      developmental processes, such as precisely regulated germ cell differentiation
      during spermatogenesis. Here we examine for the first time the dynamic
      association of importins with cargo during two successive spermatogenic stages:
      meiotic pachytene spermatocytes and haploid round spermatids of the adult rat
      testis. Immunoprecipitation followed by mass spectrometry yielded the first non
      biased identification of proteins selectively interacting with importin alpha2,
      alpha3 and alpha4 in each of these cell types. Amongst the 22 novel importin
      binding proteins identified, 11 contain a predicted classical nuclear
      localization signal (cNLS) for importin alpha binding using a new algorithm
      (Kosugi et al. [22]), although only 6 of these have known nuclear functions. An
      importin alpha2-immunoprecipitated protein with a key nuclear role in meiosis,
      structural maintenance of chromosomes 6 (SMC6), contained a predicted bipartite
      NLS that was shown to be preferentially recognized by importin alpha together
      with importin beta1. In contrast, the predicted cNLS of synovial sarcoma, X
      breakpoint 2 interacting protein (SSX2IP) was found not to confer either nuclear
      accumulation or direct binding to importin alphas, implying that NLS prediction
      algorithms may identify cryptic importin binding sites or require additional
      refinement to increase their accuracy. Unbiased identification of importin alpha
      binding proteins in cellular differentiation represents a powerful tool to help
      identify the functional roles of importin alphas.

PMID- 23159778
TI  - Impulse-dependent extracellular resting dopamine concentration in rat striatum in
      vivo.
AB  - The ambient resting dopamine (DA) concentration in brain regulates cognition and
      motivation. Despite its importance, resting DA level in vivo remains elusive.
      Here, by high-frequency stimulation of the medial forebrain bundle and
      immediately following the stimulus-induced DA overflow, we recorded a DA
      "undershoot" which is a temporal reduction of DA concentration to a level below
      the baseline. Based on the DA undershoot, we predicted a resting DA concentration
      of ~73nM in rat striatum in vivo. Simulation studies suggested that removing
      basal DA by DAT during the post-stimulation inhibition of tonic DA release caused
      the DA undershoot, and the resting concentration of DA modulated the kinetics of
      the evoked DA transient. The DA undershoot was eliminated by either blocking D2
      receptors with haloperidol or blocking the DA transporter (DAT) with cocaine.
      Therefore, the impulse-dependent resting DA concentration is in the tens of
      nanomolar range and is modulated by the presynaptic D2 receptors and the DAT in
      vivo.

PMID- 23159779
TI  - Differential regulation of evoked and spontaneous neurotransmitter release by C
      terminal modifications of complexin.
AB  - Complexins are small alpha-helical proteins that modulate neurotransmitter
      release by binding to SNARE complexes during synaptic vesicle exocytosis. They
      have been found to function as fusion clamps to inhibit spontaneous synaptic
      vesicle fusion in the absence of Ca(2+), while also promoting evoked
      neurotransmitter release following an action potential. Complexins consist of an
      N-terminal domain and an accessory alpha-helix that regulates the activating and
      inhibitory properties of the protein, respectively, and a central alpha-helix
      that binds the SNARE complex and is essential for both functions. In addition,
      complexins contain a largely unstructured C-terminal domain whose role in
      synaptic vesicle cycling is poorly defined. Here, we demonstrate that the C
      terminus of Drosophila complexin (DmCpx) regulates localization to synapses and
      that alternative splicing of the C-terminus can differentially regulate
      spontaneous and evoked neurotransmitter release. Characterization of the single
      DmCpx gene by mRNA analysis revealed expression of two alternatively expressed
      isoforms, DmCpx7A and DmCpx7B, which encode proteins with different C-termini
      that contain or lack a membrane tethering prenylation domain. The predominant
      isoform, DmCpx7A, is further modified by RNA editing within this C-terminal
      region. Functional analysis of the splice isoforms showed that both are similarly
      localized to synaptic boutons at larval neuromuscular junctions, but have
      differential effects on the regulation of evoked and spontaneous fusion. These
      data indicate that the C-terminus of Drosophila complexin regulates both
      spontaneous and evoked release through separate mechanisms and that alternative
      splicing generates isoforms with distinct effects on the two major modes of
      synaptic vesicle fusion at synapses.

PMID- 23159781
TI  - Accuracy of three automated 25-hydroxyvitamin D assays in hemodialysis patients.
AB  - INTRODUCTION: We evaluated the accuracy of three automated assays for 25(OH)D
      measurement in comparison to ID-XLC-MS/MS in hemodialysis patients, considering
      the importance of their vitamin D status and reported discrepant results obtained
      with automated assays. METHODS: All three assays were heterogeneous, competitive
      immunoassays or vitamin D binding protein assays on Architect (Abbott), Modular
      E170 (Roche) and iSYS (IDS). Measurements were performed in serum of 99
      hemodialysis patients and 50 healthy subjects, double blind with a different
      operator and aliquot for each method. RESULTS: Architect showed the highest
      deviation for hemodialysis (slope 0.3864, intercept 8.7409) and healthy subjects
      (slope 0.5024, intercept 6.8426) and reported significant lower results.
      Considering 30 ng/ml as cut-off for optimal 25(OH)D concentration, Architect
      falsely assigned 48.5% of the hemodialysis and 6% of the healthy subgroup a
      suboptimal vitamin D status. iSYS results of hemodialysis patients also deviated
      (slope 0.6136, intercept 8.6604) but showed less discordant values than Modular
      E170 in patients with 25(OH)D concentrations between 10 and 40 ng/ml. CONCLUSION:
      We conclude that not all automated 25(OH)D assays may be considered equally
      accurate in samples from hemodialysis patients compared to samples from healthy
      subjects. We found most deviating results with Abbott (Architect) measurements
      compared to ID-XLC-MS/MS in hemodialysis patients as well as in healthy subjects.
      We suggest a possible role of matrix effects like elevated urea or other retained
      metabolites in hemodialysis sera, causing incomplete binding disruption between
      25(OH)D and DBP, in the poor assay accuracy.

PMID- 23159780
TI  - The role of autophagy in Nmnat-mediated protection against hypoxia-induced
      dendrite degeneration.
AB  - The selective degeneration of dendrites precedes neuronal cell death in hypoxia
      ischemia (HI) and is a neuropathological hallmark of stroke. While it is clear
      that a number of different molecular pathways likely contribute to neuronal cell
      death in HI, the mechanisms that govern HI-induced dendrite degeneration are
      largely unknown. Here, we show that the NAD synthase nicotinamide mononucleotide
      adenylyltransferase (Nmnat) functions endogenously to protect Drosophila class IV
      dendritic arborization (da) sensory neurons against hypoxia-induced dendritic
      damage. Whereas dendrites of wild-type class IV neurons are largely resistant to
      morphological changes during prolonged periods of hypoxia (<1.0% O(2)), class IV
      neurons of nmnat heterozygous mutants exhibit significant dendrite loss and
      extensive fragmentation of the dendritic arbor under the same hypoxic conditions.
      Although basal levels of autophagy are required for neuronal survival, we
      demonstrate that autophagy is dispensable for maintaining the dendritic integrity
      of class IV neurons. However, we find that genetically blocking autophagy can
      suppress hypoxia-induced dendrite degeneration of nmnat heterozygous mutants in a
      cell-autonomous manner, suggestive of a self-destructive role for autophagy in
      this context. We further show that inducing autophagy by overexpression of the
      autophagy-specific kinase Atg1 is sufficient to cause dendrite degeneration of
      class IV neurons under hypoxia and that overexpression of Nmnat fails to protect
      class IV dendrites from the effects of Atg1 overexpression. Our studies reveal an
      essential neuroprotective role for endogenous Nmnat in hypoxia and demonstrate
      that Nmnat functions upstream of autophagy to mitigate the damage incurred by
      dendrites in neurons under hypoxic stress.

PMID- 23159782
TI  - The effect of cigarette smoke and arsenic exposure on urothelial carcinoma risk
      is modified by glutathione S-transferase M1 gene null genotype.
AB  - Inter-individual variation in the metabolism of xenobiotics, caused by factors
      such as cigarette smoking or inorganic arsenic exposure, is hypothesized to be a
      susceptibility factor for urothelial carcinoma (UC). Therefore, our study aimed
      to evaluate the role of gene-environment interaction in the carcinogenesis of UC.
      A hospital-based case-control study was conducted. Urinary arsenic profiles were
      measured using high-performance liquid chromatography-hydride generator-atomic
      absorption spectrometry. Genotyping was performed using a polymerase chain
      reaction-restriction fragment length polymorphism technique. Information about
      cigarette smoking exposure was acquired from a lifestyle questionnaire.
      Multivariate logistic regression was applied to estimate the UC risk associated
      with certain risk factors. We found that UC patients had higher urinary levels of
      total arsenic, higher percentages of inorganic arsenic (InAs%) and
      monomethylarsonic acid (MMA%) and lower percentages of dimethylarsinic acid
      (DMA%) compared to controls. Subjects carrying the GSTM1 null genotype had
      significantly increased UC risk. However, no association was observed between
      gene polymorphisms of CYP1A1, EPHX1, SULT1A1 and GSTT1 and UC risk after
      adjustment for age and sex. Significant gene-environment interactions among
      urinary arsenic profile, cigarette smoking, and GSTM1 wild/null polymorphism and
      UC risk were observed after adjustment for potential risk factors. Overall, gene
      environment interactions simultaneously played an important role in UC
      carcinogenesis. In the future, large-scale studies should be conducted using tag
      SNPs of xenobiotic-metabolism-related enzymes for gene determination.

PMID- 23159783
TI  - [The application of do not resuscitate orders and withholding treatment in
      patients admitted to Internal Medicine in a first level hospital].
AB  - OBJECTIVES: To determine the practice and associated factors of limiting
      therapeutic effort and do not resuscitate (DNR) order in a general Internal
      Medicine ward in a regional hospital. MATERIAL AND METHODS: A retrospective
      search was performed to find patients who received do not resuscitate orders and
      patients who died, among those admitted to Internal Medicine between January and
      May 2011 at the Hospital of Villarrobledo. The limitation in therapeutic effort
      (LTE) in this group is described. RESULTS: A total of 106 cases were analyzed, 80
      of them received DNR (10.28% of admissions during this period). Fifty four
      patients received other LTE. The information on the reasons and communication
      with the patient and family was incomplete in most cases. No differences were
      found between patients who died with and without LTE or with and without DNR
      orders. CONCLUSIONS: The information on the reasons that lead to LTE/DNR orders
      decisions should be improved, as well as the information on the people involved
      in these decisions.

PMID- 23159784
TI  - [Inappropriate prescribing according to Beers criteria in cardiology and
      respiratory medicine departments].

PMID- 23159785
TI  - [Predictors of patient satisfaction with the food services in a public hospital
      in Madrid].
AB  - OBJECTIVE: To describe patients satisfaction with the food services during
      hospitalisation, and to determine the predictors. METHODOLOGY: A cross-sectional
      study was conducted in the "Clinico San Carlos" Hospital, between May and
      September 2010. A self-completion questionnaire was given to patients with both
      regular and therapeutic diets after their hospital discharge. We included socio
      demographic variables, overall satisfaction, and satisfaction regarding different
      aspects and types of food. Descriptive and multivariable analyses were performed,
      with the overall satisfaction with food as the dependent variable using binary
      logistic regression. RESULTS: A total of 549 questionnaires were returned (rate
      29%), of which 60.7% received a therapeutic diet. 55.4% were men, and the median
      age was 68 years. Three-quarters (75%) were satisfied or very satisfied.
      Statistically significant variables associated with patient satisfaction with the
      food services received were the meal's taste and temperature, as well as being
      satisfied with the fish and soups on the menu. CONCLUSIONS: Despite the high
      level of satisfaction with food services, there is scope for improvement. We have
      identified some of the aspects on which action would be more beneficial.

PMID- 23159787
TI  - Effect of rhythmic auditory cueing on gait in people with Alzheimer disease.
AB  - OBJECTIVE: To determine whether rhythmic music and metronome cues alter
      spatiotemporal gait measures and gait variability in people with Alzheimer
      disease (AD). DESIGN: A repeated-measures study requiring participants to walk
      under different cueing conditions. SETTING: University movement laboratory.
      PARTICIPANTS: Of the people (N=46) who met study criteria (a diagnosis of
      probable AD and ability to walk 100m) at routine medical review, 30 (16 men; mean
      age +/- SD, 80+/-6y; revised Addenbrooke's Cognitive Examination range, 26-79)
      volunteered to participate. INTERVENTIONS: Participants walked 4 times over an
      electronic walkway synchronizing to (1) rhythmic music and (2) a metronome set at
      individual mean baseline comfortable speed cadence. MAIN OUTCOME MEASURES: Gait
      spatiotemporal measures and gait variability (coefficient of variation [CV]).
      Data from individual walks under each condition were combined. A 1-way repeated
      measures analysis of variance was used to compare uncued baseline, cued, and
      retest measures. RESULTS: Gait velocity decreased with both music and metronome
      cues compared with baseline (baseline, 110.5cm/s; music, 103.4cm/s; metronome,
      105.4cm/s), primarily because of significant decreases in stride length
      (baseline, 120.9cm; music, 112.5cm; metronome, 114.8cm) with both cue types. This
      was coupled with increased stride length variability compared with baseline
      (baseline CV, 3.4%; music CV, 4.3%; metronome CV, 4.5%) with both cue types.
      These changes did not persist at (uncued) retest. Temporal variability was
      unchanged. CONCLUSIONS: Rhythmic auditory cueing at comfortable speed tempo
      produced deleterious effects on gait in a single session in this group with AD.
      The deterioration in spatial gait parameters may result from impaired executive
      function associated with AD. Further research should investigate whether these
      instantaneous cue effects are altered with more practice or with learning methods
      tailored to people with cognitive impairment.

PMID- 23159786
TI  - The role of microparticles in the generation of immune complexes in murine lupus.
AB  - Systemic lupus erythematosus is a systemic inflammatory disease characterized by
      antibodies to nuclear molecules in association with immune complex deposition. As
      shown previously, microparticles (MPs), which are small membrane-bound vesicles
      released from dying and activated cells, contain nucleic acids and can form
      immune complexes found in patient blood. To assess the role of MPs in murine
      lupus, we used flow cytometry to measure the presence of MPs with bound IgG in
      the blood of MRL-lpr/lpr and NZB/W mice. These studies showed much higher numbers
      of MPs with bound IgG in the blood of MRL lpr/lpr compared to NZB/W mice.
      Furthermore, these studies showed that antibodies from MRL-lpr/lpr mice bound
      better to MPs from apoptotic cells than those from NZB/W mice. Together, these
      studies indicate important differences in the serological features of the two
      strains as reflected by the capacity of antibodies to bind to MPs.

PMID- 23159788
TI  - The cardiovascular effects of a chimeric opioid peptide based on morphiceptin and
      PFRTic-NH2.
AB  - MCRT (YPFPFRTic-NH(2)) is a chimeric opioid peptide based on morphiceptin and
      PFRTic-NH(2). In order to assess the cardiovascular effect of MCRT, it was
      administered by intravenous (i.v.) injection targeting at the peripheral nervous
      system and by intracerebroventricular (i.c.v.) injection targeting at the central
      nervous system. Naloxone and L-NAME were injected before MCRT to investigate
      possible interactions with MCRT. Results show that administration of MCRT by i.v.
      or i.c.v. injection could induce bradycardia and decrease in mean arterial
      pressure (MAP) at a greater degree than that with morphiceptin and PFRTic-NH(2).
      When MCRT and NPFF were coinjected, we observed a dose-dependent weakening of
      these cardiovascular effects by MCRT. Because naloxone completely abolished the
      cardiovascular effects of MCRT, we conclude that opioid receptors are involved in
      regulating the MAP of MCRT regardless of modes of injection. The effect of MCRT
      on heart rate is completely dependent on opioid receptors when MCRT was
      administered by i.c.v. instead of i.v. The central nitric oxide (NO) pathway is
      involved in regulating blood pressure by MCRT under both modes of injection, but
      the peripheral NO pathway had no effect on lowering blood pressure mediated by
      MCRT when it was administered by i.c.v. Based on the results from different modes
      of injection, the regulation of heart rate by MCRT mainly involves in the central
      NO pathway. Lastly, we observed that the cardiovascular effects of MCRT such as
      bradycardia and decrease of blood pressure, were stronger than that of its parent
      peptides. Opioid receptors and the NO pathway are involved in the cardiovascular
      regulation by MCRT, and their degree of involvement differs between intravenous
      and intracerebroventricular injection.

PMID- 23159789
TI  - Phylogenetic distribution of protease inhibitors of the Kazal-family within the
      Arthropoda.
AB  - In mammalian pancreatic cells, the pancreatic secretory trypsin inhibitor (PSTI)
      belonging to the Kazal-family prevents the premature activation of digestive
      enzymes and thus plays an important role in a protective mechanism against tissue
      destruction by autophagy. Although a similar protective mechanism exists in
      Arthropoda, the distribution of these inhibitors in this phylum remains obscure.
      A comprehensive in silico search of nucleotide databases, revealed the presence
      of members of the Kazal-family in the four major subphyla of the Arthropoda.
      Especially in the Hexapoda and the Crustacea these inhibitors are widespread,
      while in the Chelicerata and Myriapoda only a few Kazal-like protease inhibitors
      were found. A sequence alignment of inhibitors retrieved in the digestive system
      of insects revealed a conservation of the PSTI characteristics and strong
      resemblance to vertebrate PSTI. A phylogenetic analysis of these inhibitors
      showed that they generally cluster according to their order. The results of this
      data mining study provide new evidence for the existence of an ancient protective
      mechanism in metazoan digestive systems. Kazal-like inhibitors, which play an
      important protective role in the pancreas of vertebrates, also seem to be present
      in Arthropoda.

PMID- 23159790
TI  - Purification and structural characterisation of phospholipase A1 (Vespapase, Ves
      a 1) from Thai banded tiger wasp (Vespa affinis) venom.
AB  - The Thai banded tiger wasp (Vespa affinis) is one of the most dangerous vespid
      species in Southeast Asia, and stinging accidents involving this species still
      cause fatalities. In the present study, four forms of V. affinis phospholipase
      A(1) were identified through a proteomics approach. Two of these enzymes were
      purified by reverse-phase chromatography, and their biochemical properties were
      characterised. These enzymes, designated Ves a 1s, are not glycoproteins and
      exist as 33441.5 and 33474.4 Da proteins, which corresponded with the 34-kDa band
      observed via SDS-PAGE. The thermal stabilities of these enzymes were stronger
      than snake venom. Using an in vivo assay, no difference was found in the
      toxicities of the different isoforms. Furthermore, the toxicity of these enzymes
      does not appear to be correlated with their PLA(1) activity. The cDNAs of the
      full-length version of Ves a 1s revealed that the Ves a 1 gene consists of a 1005
      bp ORF, which encodes 334 amino acid residues, and 67- and 227-bp 5' and 3' UTRs,
      respectively. The two isoforms are different by three nucleotide substitutions,
      resulting in the replacement of two amino acids. Through sequence alignment,
      these enzymes were classified as members of the pancreatic lipase family. The
      structural modelling of Ves a 1 used the rat pancreatic lipase-related protein 2
      (1bu8A) as a template because it has PLA(1) activity, which demonstrated that
      this enzyme belongs to the alpha/beta hydrolase fold family. The Ves a 1
      structure, which is composed of seven alpha-helixes and eleven beta-strands,
      contains the beta-strand/ESer/alpha-helix structural motif, which contains the
      Gly-X-Ser-X-Gly consensus sequence. The typical surface structures that play
      important roles in substrate selectivity (the lid domain and the beta9 loop) were
      shortened in the Ves a 1 structure, which suggests that this enzyme may only
      exhibit phospholipase activity. Moreover, the observed insertion of proline into
      the lid domain of the Ves a 1 structure is rare. We therefore propose that this
      proline residue might be involved in the stability and activity of Ves a 1s.

PMID- 23159791
TI  - Gene expression analysis by ESTs sequencing of the Brazilian frog Phyllomedusa
      nordestina skin glands.
AB  - The subfamily Phyllomedusinae has attracted a great interest of many researchers
      mainly due to the high diversity of these frog species and plethora of
      pharmacological activities frequently observed for their skin secretions. Despite
      of this fact, mainly for new species, limited information is available regarding
      the molecular composition of these skin secretions and the cellular components
      involved in their production. Phyllomedusa nordestina is a recently described
      Brazilian frog species also popularly known as 'tree-frogs'. Aiming at
      contributing to the biological knowledge of this species, we show here the gene
      expression profile of this frog skin secretion using a global ESTs analysis of a
      cDNA library. The marked aspect of this analysis revealed a significant higher
      transcriptional level of the opioid peptide dermorphins in P. nordestina skin
      secretion than in Phyllomedusa hypochondrialis, which is its closest related
      species, belonging both to the same phylogenetic group. Precursors of bioactive
      peptides as dermaseptins, phylloseptins, tryptophyllins, and bradykinin-like
      peptideswere also found in this library. Transcripts encoding proteins related to
      ordinary cellular functions and pathways were also described. Some of them are
      chiefly involved in the production of the skin secretion. Taken together, the
      data reported here constitute a contribution to the characterization of the
      molecular diversity of gene-encoded polypeptides with potential possibility of
      pharmacological exploitation. The transcriptional composition of the skin
      secretion may also help to give the necessary support for the definition of P.
      nordestina as a new species, which actually relies basically on frog
      morphological characteristics and geographical distribution.

PMID- 23159792
TI  - [Presence and adequacy of pharmaceutical preparations in the Spanish edition of
      Wikipedia].
AB  - OBJECTIVE: To determine the presence, and to evaluate the adequacy of
      pharmaceutical preparations in the Spanish edition of Wikipedia. DESIGN:
      Descriptive cross-sectional study. SETTING: the terms studied were obtained from
      the Vademecum, UBM Medica Spain S.A, (http://vademecum.es). PARTICIPANTS: the
      sample was calculated by simple random sampling without replacement from the
      active ingredients present in the Vademecum, making the estimation of population
      parameters (expected value of approximately 0.5; 0.05 range accuracy and
      confidence level=0.95) in an infinite population. METHOD: The existence and
      adequacy of the terminology was observed by accessing the Spanish edition of
      Wikipedia. The term was considered adequate when the information contained the
      proper use, dosage and adverse effects. MAIN MEASUREMENTS: The qualitative binary
      variable yes/no (presence of the pharmaceutical drug, use, posology, adverse
      effects, adequacy) were described by frequency and percentage, quantitative
      (number of queries, update) using mean and standard deviation. The existences of
      an association between qualitative variables were analyzed using chi-square, and
      significance of the differences of means for independent samples, using the
      Student t test. RESULTS: Of the sample studied (n=386), 171 terms were found,
      with 15 being adequate. Significant differences were observed between adequacy
      and dose (P<.001) and adverse effects (P<.001), but not with use (P=.193).
      CONCLUSIONS: Pharmaceutical preparation entries in the Spanish edition of
      Wikipedia are still insufficient and the adequacy of the information remains
      inconsistent.

PMID- 23159793
TI  - [Diagnosis of heart failure with preserved or reduced ejection fraction in a one
      stop clinic].
AB  - OBJECTIVES: a) To assess the usefulness of a one-stop clinic for the diagnosis of
      outpatients with new onset heart failure; b) to characterize these patients
      comparing preserved (HF-PEF) versus reduced ejection fraction (HF-REF), and c) to
      determine brain natriuretic peptide (BNP) cut-off limit to identify HF in
      outpatients. DESIGN: Observational descriptive study. SETTING: Primary care.
      PARTICIPANTS AND MEASUREMENTS: A total of 143 outpatients with new onset HF were
      assessed in a one-stop clinic. A cardiologist evaluation, electrocardiogram,
      chest X-ray, BNP, and echocardiography (diastolic and systolic study) were
      performed. RESULTS: Almost two-thirds (65.7%) were diagnosed with HF: 67% with HF
      PEF and 33% HF-REF. Women (71.4% versus 38.7%, P=.002), presence of swelling
      ankles (61.9% versus 35.5%, P=.016) and higher body mass index (29.8+/-5.1 versus
      27.2+/-5.0 P=.021) were more frequent in the first group of patients.
      Echocardiographic signs of diastolic dysfunction and pulmonary hypertension were
      found in both groups, with higher values of BNP (153.3+/-123.1 versus 400.8+/
      579.8 P=.025) and troponin I (0.024+/-0.019 versus 0.071+/-0.12, P=.037) in HF
      REF patients. Female gender and swelling ankles were predictors of HF-PEF in the
      multivariate analysis, while Q waves and higher values of BNP and heart rate were
      predictors of HF-REF. A cut-off value of 60.12 pg/ml for BNP provided 83%
      sensitivity, 84% specificity (AUC=0.898; 95% CI; 0.848-0.948; P <.001).
      CONCLUSIONS: The one-stop HF clinic has diagnosed and characterized outpatients
      with new onset HF and high prevalence of HF-PEF. The cut-off value of 60.12 pg/ml
      for BNP provides high sensitivity and specificity to identify HF in this
      population.

PMID- 23159794
TI  - [To enlighten and to dazzle: a case of an inadequate prescription of prasugrel
      with an adverse reaction of urticaria].

PMID- 23159795
TI  - Organotypic hippocampal slice culture from the adult mouse brain: a versatile
      tool for translational neuropsychopharmacology.
AB  - One of the most significant barriers towards translational neuropsychiatry would
      be an unavailability of living brain tissues. Although organotypic brain tissue
      culture could be a useful alternative enabling observation of temporal changes
      induced by various drugs in living brain tissues, a proper method to establish a
      stable organotypic brain slice culture system using adult (rather than neonatal)
      hippocampus has been still elusive. In this study, we evaluated our simple method
      using the serum-free culture medium for successful adult organotypic hippocampal
      slice culture. Several tens of hippocampal slices from a single adult mouse (3-5
      months old) were cultured in serum-free versus serum-containing conventional
      culture medium for 30 days and underwent various experiments to validate the
      effects of the existence of serum in the culture medium. Neither the excessive
      regression of neuronal viability nor metabolic deficiency was observed in the
      serum-free medium culture in contrast to the serum-containing medium culture.
      Despite such viability, newly generated immature neurons were scarcely detected
      in the serum-free culture, suggesting that the original neurons in the brain
      slice persist rather than being replaced by neurogenesis. Key structural features
      of in vivo neural tissue constituting astrocytes, neural processes, and pre- and
      post-synapses were also well preserved in the serum-free culture. In conclusion,
      using the serum-free culture medium, the adult hippocampal slice culture system
      will serve as a promising ex vivo tool for various fields of neuroscience,
      especially for studies on aging-related neuropsychiatric disorders or for high
      throughput screening of potential agents working against such disorders.

PMID- 23159796
TI  - Decreased interhemispheric resting-state functional connectivity in first
      episode, drug-naive major depressive disorder.
AB  - BACKGROUND: Major depressive disorder (MDD) is shown to have structural and
      functional abnormalities in specific brain areas and connections by recent
      neuroimaging studies. However, little is known about the alterations of the
      interhemispheric resting-state functional connectivity (FC) in patients with MDD.
      In the present study, we used a newly developed voxel-mirrored homotopic
      connectivity (VMHC) method to investigate the interhemispheric FC of the whole
      brain in patients with MDD at rest. METHODS: Twenty-four first-episode, drug
      naive patients with MDD and 24 age-, gender-, and education-matched healthy
      subjects underwent a resting-state functional magnetic resonance imaging (fMRI).
      An automated VMHC approach was used to analyze the data. RESULTS: Patients with
      MDD showed lower VMHC than healthy subjects in the medial prefrontal cortex
      (MPFC) and the posterior cingulate cortex/precuneus (PCC/PCu), two core regions
      within default mode network (DMN). Both left and right MPFC showed reduced FC
      with the other frontal areas and with right anterior cingulate gyrus (ACC), while
      PCC/PCu exhibited abnormal FC with the frontal areas and thalamus in patient
      group. Significant positive correlation was observed between VMHC in MPFC and
      persistent error response of Wisconsin Card Sorting Test (WCST-Pre) in patients.
      Further ROC analysis revealed that VMHC in the MPFC and PCC/PCu could be used to
      differentiate the patients from healthy subjects with relatively high sensitivity
      and specificity. CONCLUSIONS: Our results suggest that decreased VMHC in brain
      regions within DMN may underlie the pathogenesis of MDD.

PMID- 23159797
TI  - Two-step labeling of Staphylococcus aureus with Lysostaphin-Azide and DIBO-Alexa
      using click chemistry.
AB  - Specific bacteria imaging is highly desirable in clinical diagnostics. Probes
      enabling rapid and specific diagnostics of bacteria are limited. Current clinical
      infection diagnostics is time consuming and invasive, relies on microbiological
      cultures. We investigated the potential of Lysostaphin as a specific probe to
      label staphylococci in a new labeling protocol. We used azido (N(3))-modified
      Lysostaphin-N(3) and DIBO-dye in a two-step bacteria-labeling protocol. N(3) and
      DIBO (di-benzocyclooctyne) are the counterparts of the "click" chemistry. In the
      first step, Lysostaphin-N(3) binds specifically to Staphylococcus aureus. In the
      second step, N(3) clicks to DIBO thus achieving the selective for S. aureus
      labeling. Such a two-step approach effectively distinguishes S. aureus from
      Escherichia coli; non-toxic and was proven to work in vivo. The two-step labeling
      protocol is a promising approach for diagnostic imaging of staphylococcal
      infections in clinical settings.

PMID- 23159798
TI  - Validation of a Poisson-distributed limiting dilution assay (LDA) for a rapid and
      accurate resolution of multiclonal infections in natural Trypanosoma cruzi
      populations.
AB  - Trypanosoma cruzi is the causative agent of American trypanosomiasis, a complex
      zoonotic disease that affects more than 10million people in the Americas. Strains
      of this parasite possess a significant amount of genetic variability and hence
      can be divided into at least six discrete typing units (DTUs). The life cycle of
      this protist suggests that multiclonal infections may emerge due to the
      likelihood of contact of triatomine insects with more than 100 mammal species. To
      date, there have been a few studies on but no consensus regarding standardised
      methodologies to identify multiclonal infections caused by this parasite. Hence,
      the aim of this study was to develop and validate a limiting dilution assay (LDA)
      to identify multiclonal infections in T. cruzi populations by comparing the
      feasibility and reliability of this method with the widely applied solid phase
      blood agar (SPBA) methodology. We cloned reference strains belonging to three
      independent genotypes (TcI, TcII, and TcIV) and mixed infections (TcI+TcII) using
      LDA and SPBA; the comparison was conducted by calculating the feasibility and
      reliability of the methods employed. Additionally, we implemented LDA in strains
      recently isolated from Homo sapiens, Rhodnius prolixus, Triatoma venosa,
      Panstrongylus geniculatus, Tamandua tetradactyla, Rattus rattus, Didelphis
      marsupialis and Dasypus novemcinctus, with the aim of resolving multiclonal
      infections using molecular characterization employing SL-IR (spliced leader
      intergenic region of mini-exon gene), the 24Salpha rDNA gene and microsatellite
      loci. The results reported herein demonstrate that LDA is an optimal methodology
      to distinguish T. cruzi subpopulations based on microsatellite markers by showing
      the absence of multiple peaks within a single locus. Conversely, SPBA showed
      patterns of multiple peaks within a single locus suggesting multiclonal events.
      The biological consequences of these results and the debate between
      multiclonality and aneuploidy are discussed.

PMID- 23159799
TI  - In-depth insight into in vivo apoplastic secretome of rice-Magnaporthe oryzae
      interaction.
AB  - The in vivo apoplastic fluid secretome of rice-blast fungus interaction remains
      largely uncharacterized. Here, we report a proteomics investigation of in vivo
      secreted proteins of rice leaves infected with incompatible (KJ401) and
      compatible (KJ301) races of Magnaporthe oryzae (M. oryzae) using 2-DGE and MudPIT
      coupled with MALDI-TOF-MS and/or nESI-LC-MS/MS analyses. Prepared fractions of
      secretory proteins were essentially free from cytoplasmic contamination. Two-DGE
      and MudPIT identified 732 secretory proteins, where 291 (40%) and 441 (60%)
      proteins were derived from rice and M. oryzae, respectively. Of these, 39.2%
      (rice) and 38.9% (M. oryzae) of proteins were predicted by SignalP as retaining
      signal peptides. Among these, rice secreted more proteins related to stress
      response, ROS and energy metabolism, whereas, M. oryzae secreted more proteins
      involved in metabolism and cell wall hydrolyses. Semi-quantitative RT-PCR
      revealed their differential expression under compatible/incompatible
      interactions. In vivo expression of M. oryzae glycosyl hydrolase (GH) protein
      family members using particle bombardment driven transient expression system
      showed that four GH genes could act as effectors within host apoplast possibly
      via interaction with host membrane bound receptor. The established in vivo
      secretome serves as a valuable resource toward secretome analysis of rice-M.
      oryzae interaction.

PMID- 23159800
TI  - Can microbes be patented?
AB  - Native microorganisms in their original form cannot be patented. However,
      microbes like yeasts, bacteria, protozoa, unicellular algae, fungi, actinomycetes
      and viruses can be patented if they have been genetically modified. The process
      and the product obtained can also be patented.

PMID- 23159801
TI  - Photosensitivity of the Ni-A state of [NiFe] hydrogenase from Desulfovibrio
      vulgaris Miyazaki F with visible light.
AB  - [NiFe] hydrogenase catalyzes reversible oxidation of molecular hydrogen. Its
      active site is constructed of a hetero dinuclear Ni-Fe complex, and the oxidation
      state of the Ni ion changes according to the redox state of the enzyme. We found
      that the Ni-A state (an inactive unready, oxidized state) of [NiFe] hydrogenase
      from Desulfovibrio vulgaris Miyazaki F (DvMF) is light sensitive and forms a new
      state (Ni-AL) with irradiation of visible light. The Fourier transform infrared
      (FT-IR) bands at 1956, 2084 and 2094 cm(-1) of the Ni-A state shifted to 1971,
      2086 and 2098 cm(-1) in the Ni-AL state. The g-values of g(x)=2.30, g(y)=2.23 and
      g(z)=2.01 for the signals in the electron paramagnetic resonance (EPR) spectrum
      of the Ni-A state at room temperature varied for -0.009, +0.012 and +0.010,
      respectively, upon light irradiation. The light-induced Ni-AL state converted
      back immediately to the Ni-A state under dark condition at room temperature.
      These results show that the coordination structure of the Fe site of the Ni-A
      state of [NiFe] hydrogenase is perturbed significantly by light irradiation with
      relatively small coordination change at the Ni site.

PMID- 23159803
TI  - Mathematical prediction of freezing times of bovine semen in straws placed in
      static vapor over liquid nitrogen.
AB  - A widespread practice in cryopreservation is to freeze spermatozoa by suspending
      the straws in stagnant nitrogen vapor over liquid nitrogen (N(2)V/LN(2)) for
      variable periods of time before plunging into liquid nitrogen (-196 degrees C)
      for indefinite storage. A mathematical heat transfer model was developed to
      predict freezing times (phase change was considered) required for bull semen and
      extender packaged in 0.5ml plastic straws and suspended in static liquid nitrogen
      vapor. Thermophysical properties (i.e. thermal conductivity, specific heat,
      density, initial freezing temperature) of bovine semen and extender as a function
      of temperature were determined considering the water change of phase. The non
      stationary heat transfer partial differential equations with variable properties
      (nonlinear mathematical problem) were numerically solved considering in series
      thermal resistances (semen suspension-straw) and the temperature profiles were
      obtained for both semen suspension and plastic straw. It was observed both the
      external heat transfer coefficient in stagnant nitrogen vapor and its temperature
      (controlled by the distance from the surface of liquid nitrogen to the straw)
      affected freezing times. The accuracy of the model to estimate freezing times of
      the straws was further confirmed by comparing with experimental literature data.
      Results of this study will be useful to select "safe" holding times of bull semen
      in plastic straws placed N(2)V/LN(2) to ensure that complete freezing of the
      sample has occurred in the nitrogen vapor and avoid cryodamage when plunging in
      LN(2). Freezing times predicted by the numerical model can be applied to optimize
      freezing protocols of bull semen in straws.

PMID- 23159802
TI  - Crystal structures of acetate kinases from the eukaryotic pathogens Entamoeba
      histolytica and Cryptococcus neoformans.
AB  - Acetate kinases (ACKs) are members of the acetate and sugar kinase/hsp70/actin
      (ASKHA) superfamily and catalyze the reversible phosphorylation of acetate, with
      ADP/ATP the most common phosphoryl acceptor/donor. While prokaryotic ACKs have
      been the subject of extensive biochemical and structural characterization, there
      is a comparative paucity of information on eukaryotic ACKs, and prior to this
      report, no structure of an ACK of eukaryotic origin was available. We determined
      the structures of ACKs from the eukaryotic pathogens Entamoeba histolytica and
      Cryptococcus neoformans. Each active site is located at an interdomain interface,
      and the acetate and phosphate binding pockets display sequence and structural
      conservation with their prokaryotic counterparts. Interestingly, the E.
      histolytica ACK has previously been shown to be pyrophosphate (PP(i))-dependent,
      and is the first ACK demonstrated to have this property. Examination of its
      structure demonstrates how subtle amino acid substitutions within the active site
      have converted cosubstrate specificity from ATP to PP(i) while retaining a
      similar backbone conformation. Differences in the angle between domains
      surrounding the active site suggest that interdomain movement may accompany
      catalysis. Taken together, these structures are consistent with the eukaryotic
      ACKs following a similar reaction mechanism as is proposed for the prokaryotic
      homologs.

PMID- 23159804
TI  - Nocturnal activity of 11beta-hydroxy steroid dehydrogenase type 1 is increased in
      type 1 diabetic children.
AB  - AIM: The objective of this study was to investigate low-grade inflammation in
      children with type 1 diabetes (T1D) and its association with cortisol levels as
      well as its bioavailability through 11beta-hydroxy steroid dehydrogenase type 1
      (11beta-HSD1) activity. METHODS: Children with T1D (n=45) and their non-diabetic
      siblings (n=28) participated in the study. Interleukin-6 (IL-6) and high
      sensitivity C-reactive protein (CRPhs) were measured between 1400 and 1800h.
      Glucocorticoid metabolites were measured in the first morning urine on clinic day
      and 11beta-HSD1 activity was estimated by tetrahydrocortisol/tetrahydrocortisone
      (THF/THE) ratio. RESULTS: Diabetic patients presented with an increased THF/THE
      ratio compared with controls (median: 0.68 [range: 0.45-1.18] vs 0.45 [0.27
      0.98], respectively; P<10(-3)). There was no difference between diabetic patients
      and controls for IL-6 (0.6ng/mL [0.6-6.8] vs 0.6 [0.6-2.2], respectively; P=0.43)
      and CRPhs (0.4mg/L [0-7.4] vs 0.3 [0-8.2]; P=0.26, respectively). When adjusted
      for age, gender and BMI, the THF/THE ratio was significantly associated with
      CRPhs (beta=0.32, P=0.02) in diabetic patients, but not in controls. CONCLUSION:
      Low-grade inflammation assessed by plasma CRPhs and IL-6 concentrations was not
      detectable in our cohort of T1D children. Nocturnal 11beta-HSD1 activity was
      increased and associated with plasma CRPhs concentration in diabetic patients.
      These results may be explained by either a direct or inflammation-mediated effect
      of the relative hepatic lack of insulin due to subcutaneous insulin therapy.

PMID- 23159805
TI  - Synthesis pharmacological evaluation and docking studies of pyrimidine
      derivatives.
AB  - A new group of pyrimidine derivatives of indane-1,3-dione were synthesized aiming
      at the synthesis of new compounds acting as analgesic, anti-inflammatory and
      antimicrobial activity in a single component. The title compounds (3a-l) were
      synthesized from chalcone derivatives of indane-1,3-dione (2a-l) through
      cyclization reaction with urea. The synthesized compounds were characterized by
      FT-IR, (1)H NMR, mass spectral data, elemental analysis and evaluated for anti
      inflammatory, analgesic, antibacterial and antifungal activities. The most active
      compound 3e, was evaluated for its ulcerogenicity. Good anti-inflammatory
      property was observed for chlorophenyl substituted pyrimidine derivatives. It
      mainly binds with Pro 218 of 1CX2, and the ligand could have caused much
      conformational changes in the protein structure than other derivatives. It also
      exhibits good analgesic and antimicrobial agent in a single component.

PMID- 23159806
TI  - Synthesis, biological evaluation and molecular modeling of 4,6-diarylpyrimidines
      and diarylbenzenes as novel non-nucleosides HIV-1 reverse transcriptase
      inhibitors.
AB  - A series of novel 4,6-diarylpyrimidines (4,6-DAPY) and diarylbenzenes (DABE)
      compounds were synthesized and evaluated as inhibitors of human immunodeficiency
      virus type-1 (HIV-1). Among them, the most potent HIV-1 inhibitors were 8b, 8d,
      14b and 18 (EC(50) = 0.049, 0.381, 0.599 and 0.398 MUM, respectively), with HIV-1
      inhibitory activity improved or similar to nevirapine (NVP, EC(50) = 0.097 MUM)
      and delavirdine (DEV, EC(50) = 0.55 MUM). The other compounds displayed moderate
      activity (8c, EC(50) = 5.25 MUM) or were inactive (8a and 14a) against HIV-1
      replication. Molecular modeling studies were performed with the synthesized
      compounds in complex with the wild-type reverse transcriptase (RT). A correlation
      was found between the anti-HIV activity and the electrostatic energy of
      interaction with Lys101 residue. These findings enrich the SAR of these Non
      Nucleoside Reverse Transcriptase Inhibitors (NNRTIs) families.

PMID- 23159807
TI  - Design, structural and spectroscopic elucidation, and the in vitro biological
      activities of new diorganotin dithiocarbamates.
AB  - The reaction of 2,2-dimethoxy-N-methylethyllamine or 2-methyl-1,3-dioxolane with
      CS(2) in alkaline media produced two novel dithiocarbamate salts. Subsequent
      reactions with organotin halides yielded six new complexes:
      [SnMe(2){S(2)CNR(R(1))(2)}(2)] (1), [Sn(n-Bu)(2){S(2)CNR(R(1))(2)}(2)] (2),
      [SnPh(2){S(2)CNR(R(1))(2)}(2)] (3), [SnMe(2){S(2)CNR(R(2))(2)}(2)] (4), [Sn(n
      Bu)(2){S(2)CNR(R(2))(2)}(2)] (5), [SnPh(2){S(2)CNR(R(2))(2)}(2)] (6), where R =
      methyl, R(1) = CH(2)CH(OMe)(2), and R(2) = 2-methyl-1,3-dioxolane. All compounds
      were identified in terms of infrared, (1)H and (13)C NMR, and the complexes were
      also characterized using (119)Sn NMR, (119)Sn Mossbauer and X-ray
      crystallography. The biological activity of all derivatives has been screened in
      terms of IC(90) and IC(50) against Aspergillus flavus, Aspergillus niger,
      Aspergillus parasiticus, Penicillium citrinum, Curvularia senegalensis,
      Staphylococcus aureus, Listeria monocytogenes, Bacillus cereus, Streptococcus
      sanguinis, Escherichia coli, Citrobacter freundii, Salmonella typhimurium, and
      Pseudomonas aeruginosa and the results correlated well with a performed study of
      structure-activity relationship (SAR). Complexes (3), (5) and (6) displayed the
      best IC(90) and IC(50) in the presence of the fungi, greater than that of
      miconazole, used as control drug.

PMID- 23159808
TI  - Lipid-like behavior of signal sequence peptides at air-water interface.
AB  - Several protein transport processes in the cell are mediated by signal sequence
      peptides located at the N-terminal side of the mature protein sequence. To date,
      the specific interaction and the stability of these peptides at the amphipathic
      interface of biological membranes and the relevance of the peptide conformation
      when they interact with lipids is not clear. We report the surface properties and
      the peptide-lipid interaction of three signal sequence peptides at the air-NaCl
      145 mM interface by using the Langmuir monolayer approach. These synthetic
      peptides have a natural sequence with a non-periodic amphiphilicity, where
      hydrophobic and hydrophilic residues are located on opposed sides of the peptide
      primary sequence. We show that signal sequence peptides form insoluble monolayers
      of high stability against lateral compression. At close packing, peptide
      molecular area, surface potential and the high stability of the peptide monolayer
      are indicative that signal sequence peptides are compatible with a beta-sheet
      conformation at the interface. Structure was confirmed with PM-IRRAS and
      transmission FT-IR studies. The peptides show lateral miscibility with either
      POPC (a liquid-expanded lipid) or DPPC (a liquid-condensed lipid) in mixed
      peptide-lipid monolayers. This indicates that signal sequence peptides studied
      are laterally miscible with phospholipids independent of the phase state of the
      lipid.

PMID- 23159809
TI  - Cholesterol's interactions with serine phospholipids - a comparison of N
      palmitoyl ceramide phosphoserine with dipalmitoyl phosphatidylserine.
AB  - In this study we have prepared ceramide phosphoserine (CerPS) and examined its
      sterol-interacting properties. CerPS is a hydrogen-bonding sphingolipid, but its
      head group differs from that found in sphingomyelin (SM). Based on
      diphenylhexatriene steady-state anisotropy measurements, we observed that fully
      hydrated N-palmitoyl CerPS had a gel-to-liquid crystalline phase transition
      temperature of about 51 degrees C in 50mM sodium phosphate buffer (pH 7.4). This
      was close to the T(m) measured for 1,2-dipalmitoyl-sn-glycero-3-phosphoserine
      (DPPS) bilayers (T(m) 50.5 degrees C). Based on cholestatrienol (CTL) quenching
      experiments in liquid disordered ternary bilayers (containing 1-palmitoyl-2
      oleoyl-sn-glycero-3-phosphcholine; POPC), cholesterol/CTL formed sterol-enriched
      ordered domains with CerPS. These had similar thermostability as the sterol
      domains formed with N-palmitoyl SM. Cholesterol failed to form sterol-enriched
      ordered domains with DPPS under comparable conditions. Based on the equilibrium
      partitioning of CTL, we observed that the affinity of sterol for bilayers
      containing POPC/CerPS/cholesterol (6:3:1 by mol) was much higher than the
      affinity measured for control fluid POPC/cholesterol (9:1 by mol) bilayers, but
      slightly less than seen for comparable PSM-containing bilayers. We conclude that
      the phosphoserine head group was less efficient than the phosphocholine head
      group in stabilizing sterol/sphingolipid interaction. However, hydrogen bonding
      apparently can overcome some of the negative effects of the phosphoserine head
      group, since CerPS interacted more favorably with cholesterol compared to DPPS.

PMID- 23159810
TI  - Lipid-protein nanodiscs promote in vitro folding of transmembrane domains of
      multi-helical and multimeric membrane proteins.
AB  - Production of helical integral membrane proteins (IMPs) in a folded state is a
      necessary prerequisite for their functional and structural studies. In many cases
      large-scale expression of IMPs in cell-based and cell-free systems results in
      misfolded proteins, which should be refolded in vitro. Here using examples of the
      bacteriorhodopsin ESR from Exiguobacterium sibiricum and full-length
      homotetrameric K(+) channel KcsA from Streptomyces lividans we found that the
      efficient in vitro folding of the transmembrane domains of the polytopic and
      multimeric IMPs could be achieved during the protein encapsulation into the
      reconstructed high-density lipoprotein particles, also known as lipid-protein
      nanodiscs. In this case the self-assembly of the IMP/nanodisc complexes from a
      mixture containing apolipoprotein, lipids and the partially denatured protein
      solubilized in a harsh detergent induces the folding of the transmembrane
      domains. The obtained folding yields showed significant dependence on the
      properties of lipids used for nanodisc formation. The largest recovery of the
      spectroscopically active ESR (~60%) from the sodium dodecyl sulfate (SDS) was
      achieved in the nanodiscs containing anionic saturated lipid 1,2-dimyristoyl-sn
      glycero-3-phosphocholine (DMPG) and was approximately twice lower in the
      zwitterionic DMPC lipid. The reassembly of tetrameric KcsA from the acid
      dissociated monomer solubilized in SDS was the most efficient (~80%) in the
      nanodiscs containing zwitterionic unsaturated lipid 1-palmitoyl-2-oleoyl-sn
      glycero-3-phosphocholine (POPC). The charged and saturated lipids provided lower
      tetramer quantities, and the lowest yield (<20%) was observed in DMPC. The
      overall yield of the ESR and KcsA folding was mainly restricted by the efficiency
      of the protein encapsulation into the nanodiscs.

PMID- 23159811
TI  - Role of terminal dipole charges in aggregation of alpha-helix pair in the voltage
      gated K(+) channel.
AB  - The voltage sensor domain (VSD) of the potassium ion channel KvAP is comprised of
      four (S1-S4) alpha-helix proteins, which are encompassed by several charged
      residues. Apart from these charges, each peptide alpha-helix having two inherent
      equal and opposite terminal dipolar charges behave like a macrodipole. The
      activity of voltage gated ion channel is electrostatic, where all the charges
      (charged residues and dipolar terminal charges) interact with each other and with
      the transmembrane potential. There are evidences that the role of the charged
      residues dominate the stabilization of the conformation and the gating process of
      the ion channel, but the role of the terminal dipolar charges are never
      considered in such analysis. Here, using electrostatic theory, we have studied
      the role of the dipolar terminal charges in aggregation of the S3b-S4 helix pair
      of KvAP in the absence of any external field (V=0). A system attains stability,
      when its potential energy reaches minimum values. We have shown that the presence
      of terminal dipole charges (1) change the total potential energy of the charges
      on S3b-S4, affecting the stabilization of the alpha-helix pair within the bilayer
      lipid membrane and (2) the C- and the N-termini of the alpha-helices favor a
      different dielectric medium for enhanced stability. Thus, the dipolar terminal
      charges play a significant role in the aggregation of the two neighboring alpha
      helices.

PMID- 23159812
TI  - Ultrasonic atomization of tissue and its role in tissue fractionation by high
      intensity focused ultrasound.
AB  - Atomization and fountain formation is a well-known phenomenon that occurs when a
      focused ultrasound wave in liquid encounters an air interface. High intensity
      focused ultrasound (HIFU) has been shown to fractionate a tissue into submicron
      sized fragments in a process termed boiling histotripsy, wherein the focused
      ultrasound wave superheats the tissue at the focus, producing a millimetre-sized
      boiling or vapour bubble in several milliseconds. Yet the question of how this
      millimetre-sized boiling bubble creates submicron-sized tissue fragments remains.
      The hypothesis of this work is that the tissue can behave as a liquid such that
      it atomizes and forms a fountain within the vapour bubble produced in boiling
      histotripsy. We describe an experiment, in which a 2 MHz HIFU transducer (maximum
      in situ intensity of 24 000 W cm(-2)) was aligned with an air-tissue interface
      meant to simulate the boiling bubble. Atomization and fountain formation was
      observed with high-speed photography and resulted in tissue erosion. Histological
      examination of the atomized tissue showed whole and fragmented cells and nuclei.
      Air-liquid interfaces were also filmed. Our conclusion was that HIFU can fountain
      and atomize tissue. Although this process does not entirely mimic what was
      observed in liquids, it does explain many aspects of tissue fractionation in
      boiling histotripsy.

PMID- 23159813
TI  - Raised calcium and oxidative stress cooperatively promote alpha-synuclein
      aggregate formation.
AB  - Cell loss in Parkinson's and Parkinson's-plus diseases is linked to abnormal,
      aggregated forms of the cytoplasmic protein, alpha-synuclein (alpha-syn). The
      factors causing alpha-syn aggregation may include oxidative stress, changes in
      protein turnover and dysregulation of calcium homeostasis, resulting in cytotoxic
      aggregated alpha-syn species. Recently, we showed that raised calcium can promote
      alpha-syn aggregation. We have now investigated the effects of raised calcium
      combined with oxidation/oxidative stress on alpha-syn aggregation both in vitro
      and in vivo. We treated monomeric alpha-syn with calcium, hydrogen peroxide or
      calcium plus hydrogen peroxide in vitro and used size exclusion chromatography,
      fluorescence correlation spectroscopy, atomic force microscopy and scanning
      electron microscopy to investigate protein aggregation. Our in vitro data is
      consistent with a cooperative interaction between calcium and oxidation resulting
      in alpha-syn oligomers. In cell culture experiments, we used thapsigargin or
      ionophore A23187 to induce transient increases of intracellular free calcium in
      human 1321N1 cells expressing an alpha-syn-GFP construct both with and without co
      treatment with hydrogen peroxide and observed alpha-syn aggregation by
      fluorescence microscopy. Our in vivo cell culture data shows that either
      transient increase in intracellular free calcium or hydrogen peroxide treatment
      individually were able to induce significantly (P=0.01) increased 1-4MUm
      cytoplasmic alpha-syn aggregates after 12h in cells transiently transfected with
      alpha-syn-GFP. There was a greater proportion of cells positive for aggregates
      when both raised calcium and oxidative stress were combined, with a significantly
      increased proportion (P=0.001) of cells with multiple (3 or more) discrete alpha
      syn focal accumulations per cell in the combined treatment compared to raised
      calcium only. Our data indicates that calcium and oxidation/oxidative stress can
      cooperatively promote alpha-syn aggregation both in vitro and in vivo and
      suggests that oxidative stress may play an important role in the calcium
      dependent aggregation mechanism.

PMID- 23159814
TI  - Expression and functional significance of the Ca(2+)-activated Cl(-) channel ANO6
      in dendritic cells.
AB  - BACKGROUND/AIMS: Migration of dendritic cells (DCs), antigen presenting cells
      that link innate and adaptive immunity, is critical for initiation of immune
      responses. DC migration is controlled by the activity of different ion channels,
      which mediate Ca(2+) flux or set the membrane potential. Moreover, cell migration
      requires local volume changes at the leading and rear end of travelling cells,
      which might be mediated by the fluxes of osmotically active solutes, including
      Cl(-). The present study explored the functional expression, regulation and role
      of Cl(-) channels in mouse bone marrow-derived DCs. METHODS/RESULTS: In whole
      cell patch clamp experiments we detected outwardly rectifying Cl(-) currents
      which were activated by elevation of cytosolic Ca(2+), triggered either by
      ionomycin in the presence of extracellular Ca(2+) or mobilization of Ca(2+) by
      IP(3) Most importantly, Ca(2+)-activated Cl(-) channels (CaCCs) were activated by
      CCL21 (75 ng/ml), an agonist of the chemokine receptor CCR7. The currents showed
      sensitivity to Cl(-) channel blockers such as tannic acid (10 uM), digallic acid
      (100 uM) and more specific CaCC blockers niflumic acid (300 uM) and AO1 (20 uM).
      According to RT-PCR and Western blot data, Anoctamin 6 (ANO6) is expressed in
      DCs. Knock-down of ANO6 with siRNA led to inhibition of CaCC currents in DCs.
      Moreover, chemokine-induced migration of both immature and LPS-matured DCs was
      reduced upon ANO6 knock-down. CONCLUSION: Our data identify ANO6 as a Ca(2+)
      activated Cl(-) channel in mouse DCs, show its activation upon chemokine receptor
      ligation and establish an important role of ANO6 in chemokine-induced DC
      migration.

PMID- 23159815
TI  - The FACIT-AI, a new tool for assessing symptoms associated with malignant
      ascites.
AB  - OBJECTIVE: The objectives of this study are to assess the clinical relevance and
      validity of the Functional Assessment of Chronic Illness Therapy-Ascites Index
      (FACIT-AI) in women with ovarian cancer and malignant ascites, and to modify the
      instrument guided by qualitative feedback from patients with recurrent malignant
      ascites. METHODS: Fourteen adult female patients with recurrent symptomatic
      malignant ascites were enrolled from three centers. All completed an open-ended
      symptom list to identify their primary concerns regarding their condition. They
      then completed a draft 10-item FACIT-AI questionnaire created from expert input.
      Eleven patients provided comments regarding the FACIT-AI questionnaire using a
      written feedback format. Three patients participated in a "think-aloud" cognitive
      debriefing interview to ensure patient comprehension of questionnaire items.
      RESULTS: Of the first 11 patients surveyed, 7 believed that the draft FACIT-AI
      contained all important symptoms associated with malignant ascites. Responses
      from the remaining 4 patients revealed three symptoms that 2 or more patients
      nominated for inclusion: urinary frequency, constipation and emotional distress.
      These items were added to the original FACIT-AI to produce a 13-item index of
      symptoms associated with malignant ascites. CONCLUSIONS: The 13-item FACIT-AI has
      content validity among women with malignant ascites associated with ovarian
      cancer. It is available for use in clinical research or practice, with the
      expectation that more will be learned about its performance and interpretation
      over time.

PMID- 23159816
TI  - Placental site and epithelioid trophoblastic tumours: diagnostic pitfalls.
AB  - OBJECTIVE: To describe the clinical and histological pitfalls in the diagnosis of
      placental site trophoblastic tumours (PSTT) and epithelioid trophoblastic tumours
      (ETT), two rare types of gestational trophoblastic neoplasia (GTN). METHODS: This
      retrospective, observational, study was carried out in the French Trophoblastic
      Disease Reference Centre, Lyon, between 2000 and 2011. Due to the many
      similarities in the diagnosis, treatment and prognosis of PSTT and ETT, these two
      types of tumour were investigated together. Twenty-two patients with PSTT or ETT
      were analysed. RESULTS: The clinical presentation of these two types of tumour
      was irregular vaginal bleeding (55%) or amenorrhoea (27%), with a median plasma
      hCG level of 205IU/L. Seven of the 22 patients (32%) were initially misdiagnosed
      as an ectopic pregnancy. Median age at presentation was 35-years, with a median
      interval of 12months between the antecedent pregnancy and diagnosis of PSTT or
      ETT. The initial histological diagnosis was incorrect in 7/18 (39%) patients;
      there was a major disagreement with the referral pathologist in five of these
      seven patients (28%). CONCLUSIONS: PSTT and ETT are the most difficult types of
      GTN to diagnose clinically and histologically. An incorrect diagnosis can lead to
      significant therapeutic deviations from the recommended first-line treatment,
      namely hysterectomy. Clinical and histological expertise is essential to avoid
      the pitfalls in the diagnosis of PSTT and ETT.

PMID- 23159817
TI  - Effective treatment of pelvic lymphocele by lymphaticovenular anastomosis.
AB  - OBJECTIVE: Pelvic lymphocele can be a severe complication associated with
      surgical procedures such as pelvic lymphadenectomy. Lymphaticovenular anastomosis
      (LVA) is increasing in popularity as a surgical treatment for lymphedema. The aim
      of this study was to evaluate whether LVA is an effective treatment for
      lymphocele, which is caused by an obstruction of the lymphatic flow in a manner
      similar to the development of lymphedema. METHODS: Eleven female patients, who
      presented with lymphocele, were treated with LVA. Before the operation, 3 of them
      were treated with a percutaneous catheter. Lymphocele size and the volume of
      daily drainage were measured before and after LVA. RESULTS: The lymphocele was
      completely resolved in 6 patients and partially resolved in the remaining 5
      patients. The mean size of the pelvic lymphocele changed from 400 ml (range 50
      1050 ml) to 43 ml (range 0-120 ml) (P<0.01). In the 3 patients who had
      percutaneous drainage catheters, the volume of fluid drained decreased from 340
      ml/day to 20 ml/day after LVA. CONCLUSIONS: Our technique is minimally invasive
      and is performed under local anesthesia. LVA is effective regardless of the size
      of the lymphocele. Therefore, LVA should be considered as a therapy for
      lymphocele because of its low invasiveness and its effectiveness in re
      establishing circulation of lymphatic flow. Further studies should be performed
      to compare LVA with other minimally invasive techniques, such as percutaneous
      catheter and sclerotherapy.

PMID- 23159818
TI  - Postoperative pelvic intensity-modulated radiotherapy and concurrent chemotherapy
      in intermediate- and high-risk cervical cancer.
AB  - OBJECTIVE: According to national surveys, the use of intensity-modulated
      radiation therapy (IMRT) in gynecologic cancers is on the rise, yet there is
      still some reluctance to adopt adjuvant IMRT as standard practice. The purpose of
      this study is to report a single-institution experience using postoperative
      pelvic IMRT with concurrent chemotherapy in intermediate- and high-risk early
      stage cervical cancer. METHODS: From 1/2004 to 12/2009, 34 patients underwent
      radical hysterectomy and pelvic lymph node dissection (28 median nodes were
      removed) for early stage cervical cancer. Median dose of postoperative pelvic
      IMRT was 50.4 Gy (range, 45-50.4). All patients received concurrent cisplatin.
      RESULTS: With a median follow-up of 44 months, 3 patients have recurred; 1
      vaginal recurrence, 1 regional and distant, and 1 distant. The 3- and 5-year
      disease-free survival (DFS) was 91.2% (95% CI, 81.4-100%) and overall survival
      (OS) was 91.1% (95% CI, 81.3-100%). All failures and all deaths were in the high
      risk group (n=3/26). There was 32.3% G3-4 hematologic toxicity, 2.9% acute G3
      gastrointestinal toxicity, and no acute G3 or higher genitourinary toxicity.
      There were no chronic G3 or higher toxicities. CONCLUSIONS: Oncologic outcomes
      with postoperative IMRT were very good, with DFS and OS rates of >90% at median
      follow-up of 44 months, despite a preponderance (76.5%) of high-risk features.
      Toxicity was minimal even in the setting of an aggressive trimodality approach.
      Data from this study and emerging data from the Phase II RTOG study (0418)
      demonstrate the advantages of postoperative IMRT in early stage cervical cancer.

PMID- 23159819
TI  - Fabric-based Tsai-Wu yield criteria for vertebral trabecular bone in stress and
      strain space.
AB  - Osteoporosis related vertebral fractures are an increasing clinical problem in
      ageing societies. The prediction of vertebral fracture load from QCT-based
      anatomy-specific finite element simulations could be very useful in the
      management of patients with osteoporosis, especially with regard to a possible
      fracture prevention or treatment optimisation. A key property in finite element
      analysis is the yield surface for the trabecular bone material. This study is
      aimed at identifying continuum-level yield criteria for vertebral trabecular bone
      using micro-finite element models subjected to uni-axial, shear, and tri-axial
      loading. A fabric-dependent, orthotropic Tsai-Wu yield criterion is proposed in
      both stress and strain spaces. Nonlinear micro-finite element models of cubic
      vertebral trabecular bone samples with 5.62 mm edge length were generated from
      MUCT-scans. Kinematic boundary conditions were imposed and the specimen was
      loaded force controlled beyond yield in 17 different load cases (six uni-axial,
      three shear and eight multi-axial). The proposed yield criteria were fitted to
      the resulting yield data. Yield strains on-axis were significantly lower (10% in
      tension and 6% in compression) than in the transverse directions. Average yield
      strains were 0.7% in tension, 1.1% in compression, 1.0% in shear and ranged from
      0.6% to 1.1% under multi-axial loading. In axial direction, maximum yield stress
      was 2.6 MPa in tension and 4.7 MPa in compression. Lowest shear stress was found
      in the transverse plane with 1.3 MPa. Multi-axial yield stresses ranged between
      values for uni-axial tension and compression. Yield stresses depended
      significantly and substantially on both volume fraction and fabric. Yield strains
      depended also significantly on both bone volume fraction and fabric, but only
      weakly on the former. The standard error of the estimate and the concordance
      correlation coefficient of the yield surface were 5.47% and 0.93 in strain space
      and 13.58% and 0.96 in stress space. The results of this study are not only
      consistent with experimental data from the literature but also extend the current
      knowledge of yield to multi-axial load cases that can hardly be realised in a
      biomechanical experiment. The presented yield data and criteria will help
      improving the prediction of vertebral ultimate load using anatomy-specific finite
      element models.

PMID- 23159820
TI  - The influence of lung airways branching structure and diffusion time on
      measurements and models of short-range 3He gas MR diffusion.
AB  - Hyperpolarized (3)He diffusion experiments have been shown to be sensitive to
      changes in acinar structure due to emphysematous lung disease. Extracting
      quantitative information about lung microstructure from the diffusion signal is
      complicated due its dependence on a number of factors including diffusion time
      and the complex branching acinar geometry. A theoretical model (cylinder model)
      has been proposed as a means of estimating acinar airway dimensions from measured
      diffusivities. This model assumes that the effects of acinar branching geometry
      and finite airway length upon (3)He diffusion behaviour are negligible. In this
      work, we use finite element simulations of diffusion in a model of branching
      alveolar ducts to investigate in detail the effects of acinar branching structure
      and finite airway length on short-range (3)He diffusion measurements. The results
      show that branching effects have a significant influence upon (3)He diffusivity,
      even at short diffusion times. The expressions of the cylinder model theory do
      not account for significant dependences upon diffusion time, branching geometry
      and airway length, as a consequence of the oversimplified geometrical model used.
      The effect of diffusion time on (3)He ADC was also investigated through
      experiments with healthy human volunteers. The results demonstrate that the
      cylinder model can produce inaccurate estimates of the airway dimensions as a
      consequence of incompletely accounting for the diffusion-time dependence in the
      model equations and confirmed the predicted limitations of the cylinder model for
      reliable lung morphometry measurements. The results and models presented in this
      work may help in the development of a more realistic theoretical framework for
      'in vivo lung morphometry' using (3)He diffusion MR.

PMID- 23159821
TI  - HyperSPASM NMR: a new approach to single-shot 2D correlations on DNP-enhanced
      samples.
AB  - Dissolution DNP experiments are limited to a single or at most a few scans,
      before the non-Boltzmann magnetization has been consumed. This makes it
      impractical to record 2D NMR data by conventional, t(1)-incremented schemes. Here
      a new approach termed HyperSPASM to establish 2D heteronuclear correlations in a
      single scan is reported, aimed at dealing with this kind of challenge. The
      HyperSPASM experiment relies on imposing an amplitude-modulation of the data by a
      single Deltat(1) indirect-domain evolution time, and subsequently monitoring the
      imparted encoding on separate echo and anti-echo pathway signals within a single
      continuous acquisition. This is implemented via the use of alternating,
      switching, coherence selection gradients. As a result of these manipulations the
      phase imparted by a heteronucleus over its indirect domain evolution can be
      accurately extracted, and 2D data unambiguously reconstructed with a single-shot
      excitation. The nature of this sequence makes the resulting experiment
      particularly well suited for collecting indirectly-detected HSQC data on
      hyperpolarized samples. The potential of the ensuing HyperSPASM method is
      exemplified with natural-abundance hyperpolarized correlations on model systems.

PMID- 23159822
TI  - [Arterial heterogeneity].
AB  - More and more clinical observations and trials support the concept of
      heterogeneity of atheroma according to the arterial bed. In a pilot study named
      "Etude Comparative des Lesions Atheromateuses" (ECLA), we have shown that carotid
      and femoral plaques possess different characteristics. Carotid arteries display
      increased lipid content compared to femoral arteries whereas femoral arteries are
      more prone to calcify and to develop osteoid metaplasia. These observations
      should lead the researcher and the clinician to look at the cellular and
      molecular mechanisms governing the heterogeneity of atheromas. At last, a better
      understanding of the characteristics of plaques should help us to determine
      plaque stability, to prevent cardiovascular events and to choose the best
      medical, endovascular or surgical option.

PMID- 23159823
TI  - The association between SpO2 values and mortality--interpret with caution.

PMID- 23159824
TI  - "It's got potential"--an old tool used in a new way for pre-hospital detection of
      acute coronary occlusion after ventricular fibrillation.

PMID- 23159825
TI  - Use and benefits of public access defibrillation in a nation-wide network.
AB  - BACKGROUND: Automated External Defibrillators (AEDs) are known to increase
      survival after out-of-hospital cardiac arrest (OHCA). The aim of this study was
      to examine the use and benefit of public-access defibrillation (PAD) in a nation
      wide network. We primarily sought to assess survival at 1 month but information
      about the circumstances of each OHCA is provided as well. METHODS: In this 28
      month study, we assessed the use of 807 AEDs in Denmark. When an AED was deployed
      information about the circumstances of OHCA, the bystander, the AED and the
      victim's condition was obtained. RESULTS: An AED was connected to an OHCA victim
      prior to the arrival of Emergency Medical Services (EMS) in 48 instances. Ten
      percent of bystanders were off-duty healthcare professionals. Shockable arrests
      (N=31, 70%) were significantly more likely to be witnessed (94% vs. 54%) to occur
      at sports facilities (74% vs. 31%), in relation to exercise (42% vs. 0%), and
      with improved 30-day survival (69% vs. 15%, p=0.001). Among those presenting with
      a shockable rhythm, 20 (65%) had Return of Spontaneous Circulation upon arrival
      of EMS and 8 (26%) were conscious, which emphasizes the diagnostic value of ECG
      downloads from AEDs. Survival could be determined in 42 of 44 patients with OHCA
      of cardiac origin, and was 52% (n=22, 95% CI [38-67]) and the Cerebral
      Performance Category was 1 (Good Cerebral Performance) in all survivors.
      CONCLUSION: With a 30-day neurologically intact survival of 69% for patients with
      shockable rhythms, this study provides further evidence of the lifesaving
      potential of PAD.

PMID- 23159826
TI  - A reply to: Young C, Beasley R. "The association between SpO2 values and
      mortality--interpret with caution".

PMID- 23159827
TI  - Polymeric hydrogels for oral insulin delivery.
AB  - The search for an effective and reliable oral insulin delivery system has been a
      major challenge facing pharmaceutical scientists for over many decades. Even
      though innumerable carrier systems that protect insulin from degradation in the
      GIT with improved membrane permeability and biological activity have been
      developed, yet a clinically acceptable device is not available for human
      application. Efforts in this direction are continuing at an accelerated speed.
      One of the preferred systems widely explored is based on polymeric hydrogels that
      protect insulin from enzymatic degradation in acidic stomach and delivers
      effectively in the intestine. Swelling and deswelling mechanisms of the hydrogel
      under varying pH conditions of the body control the release of insulin. The micro
      and nanoparticle (NP) hydrogel devices based on biopolymers have been widely
      explored, but their applications in human insulin therapy are still far from
      satisfactory. The present review highlights the recent findings on hydrogel-based
      devices for oral delivery of insulin. Literature data are critically assessed and
      results from different laboratories are compared.

PMID- 23159828
TI  - Cohort profile: the Quebec Longitudinal Study of Kindergarten Children (QLSKC).
AB  - The Quebec Longitudinal Study of Kindergarten Children (QLSKC) is an ongoing
      population-based prospective longitudinal study presently spanning ages 6-29
      years, designed to study the prevalence, risk factors, development and
      consequences of behavioural and emotional problems during elementary school.
      Kindergarten boys and girls attending French-speaking public schools in the
      Canadian province of Quebec during the 1986-87 and 1987-88 school years were
      included in the cohort: 2000 children representative of the population and 1017
      children exhibiting disruptive behaviour problems. To date, 12 waves of data have
      been collected, and three generations of participants have been involved in the
      study (i.e. the study child, his parents and the first child of the study child).
      Information on demographics, psycho-social and lifestyle factors, child and
      family member characteristics (physical and mental health), and outcomes such as
      psychiatric diagnoses, delinquency or school diploma were assessed during three
      important developmental stages (childhood, adolescence and early adulthood).
      Blood samples were also collected in early adulthood for genetic analyses.
      Information on publications, available data and access to data can be found on
      the following website (http://www.gripinfo.ca/Grip/Public/www/). 

PMID- 23159829
TI  - Cell phone use and traffic crash risk: a culpability analysis.
AB  - BACKGROUND: The use of a cell phone or communication device while driving is
      illegal in many jurisdictions, yet evidence evaluating the crash risk associated
      with cell phone use in naturalistic settings is limited. This article aims to
      determine whether cell phone use while driving increases motor vehicle crash
      culpability. Method Drivers involved in crashes where police reported cell phone
      use (n = 312) and propensity matched drivers (age, sex, suspect alcohol/drug
      impairment, crash type, date, time of day, geographical location) without cell
      phone use (n = 936) were drawn from Insurance Corporation of British Columbia
      Traffic Accident System data. A standardized scoring tool, modified to account
      for Canadian driving conditions, was used to determine crash culpability from
      police reports on all drivers from the crashes. The association between crash
      culpability and cell phone use was determined, with additional subgroup analyses
      based on crash severity, driver characteristics and type of licence. RESULTS: A
      comparison of crashes with vs without cell phones revealed an odds ratio of 1.70
      (95% confidence interval 1.22-2.36; P = 0.002). This association was consistent
      after adjustment for matching variables and other covariates. Subgroup analyses
      demonstrated an association for male drivers, unimpaired drivers, injured and non
      injured drivers, and for drivers aged between 26 and 65 years. CONCLUSIONS: Crash
      culpability was found to be significantly associated with cell phone use by
      drivers, increasing the odds of a culpable crash by 70% compared with drivers who
      did not use a cell phone. This increased risk was particularly high for middle
      aged drivers.

PMID- 23159830
TI  - Data resource profile: the Rochester Epidemiology Project (REP) medical records
      linkage system.
AB  - The Rochester Epidemiology Project (REP) medical records-linkage system was
      established in 1966 to capture health care information for the entire population
      of Olmsted County, MN, USA. The REP includes a dynamic cohort of 502 820 unique
      individuals who resided in Olmsted County at some point between 1966 and 2010,
      and received health care for any reason at a health care provider within the
      system. The data available electronically (electronic REP indexes) include
      demographic characteristics, medical diagnostic codes, surgical procedure codes
      and death information (including causes of death). In addition, for each
      resident, the system keeps a complete list of all paper records, electronic
      records and scanned documents that are available in full text for in-depth review
      and abstraction. The REP serves as the research infrastructure for studies of
      virtually all diseases that come to medical attention, and has supported over
      2000 peer-reviewed publications since 1966. The system covers residents of all
      ages and both sexes, regardless of socio-economic status, ethnicity or insurance
      status. For further information regarding the use of the REP for a specific
      study, please visit our website at www.rochesterproject.org or contact us at
      info@rochesterproject.org. Our website also provides access to an introductory
      video in English and Spanish.

PMID- 23159832
TI  - Influence of aging on Bmal1 and Per2 expression in extra-SCN oscillators in
      hamster brain.
AB  - Deletion of the core clock gene, Bmal1, ablates circadian rhythms and accelerates
      aging, leading to cognitive deficits and tissue atrophy (e.g., skeletal muscle)
      (Kondratov et al., 2006, Kondratova et al., 2010). Although normal aging has been
      shown to attenuate Bmal1 expression in the master circadian pacemaker in the
      suprachiasmatic nucleus (SCN), relatively little is known about age-related
      changes in Bmal1 expression in other tissues, where Bmal1 may have multiple
      functions. This study tested the hypothesis that aging reduces Bmal1 expression
      in extra-SCN oscillators including brain substrates for memory and in skeletal
      muscle. Brains and gastrocnemius muscles were collected from young (3-5 months)
      and old hamsters (17-21 months) euthanized at four times of day. Bmal1 mRNA
      expression was determined by conducting in situ hybridization on brain sections
      or real-time PCR on muscle samples. The results showed age-related attenuation of
      Bmal1 expression in many brain regions, and included loss of diurnal rhythms in
      the hippocampal CA2 and CA3 subfields, but no change in muscle. In situ
      hybridization for Per2 mRNA was also conducted and showed age-related reduction
      of diurnal rhythm amplitude selectively in the hippocampal CA1 and DG subfields.
      In conclusion, aging has tissue-dependent effects on Bmal1 expression in extra
      SCN oscillators. These finding on normal aging will provide a reference for
      comparing potential changes in Bmal1 and Per2 expression in age-related
      pathologies. In conjunction with previous reports, the results suggest the
      possibility that attenuation of clock gene expression in some brain regions (the
      hippocampus, cingulate cortex and SCN) may contribute to age-related cognitive
      deficits.

PMID- 23159833
TI  - Age dependent changes of distractibility and reorienting of attention revisited:
      an event-related potential study.
AB  - Adults of three age groups (18-27, 39-45, and 59-66 years) performed an auditory
      duration discrimination task with short (200 ms) or long (400 ms) sinusoidal
      tones. Performance was highly accurate and reaction times were on the same level
      in all groups, indicating no differences in auditory duration processing. Task
      irrelevant rare changes of the frequency of the stimuli were introduced to check
      whether the subjects, firstly, were distracted by changes in the environment
      while focusing on the task relevant information (indicated by prolonged
      responses), and, secondly, could re-focus on the relevant task after distraction.
      The results show that a distraction effect is present in all groups. Importantly,
      the 59-66 years group showed a behavioral distraction effect nearly twice as high
      as the other groups. The event-related brain potentials (ERPs) show mismatch
      negativity (MMN), P3a, and reorienting negativity (RON) elicited by deviants
      which are present in all groups. Aging effects on these ERP components were
      observable in all three components but a revealed a weak significant effect for
      the MMN only. Taken together, the behavioral and ERP results suggest that the
      function of balancing the processing of task irrelevant changes in the
      stimulation while focusing on task relevant information is effective during
      adulthood until the 7th decade of life.

PMID- 23159834
TI  - Body mass index: neurosurgical perspective.

PMID- 23159831
TI  - Serotonin hyperinnervation and upregulated 5-HT2A receptor expression and motor
      stimulating function in nigrostriatal dopamine-deficient Pitx3 mutant mice.
AB  - The striatum receives serotonin (5-hydroxytryptamine, 5-HT) innervation and
      expresses 5-HT2A receptors (5-HT2ARs) and other 5-HT receptors, raising the
      possibility that the striatal 5-HT system may undergo adaptive changes after
      chronic severe dopamine (DA) loss and contribute to the function and dysfunction
      of the striatum. Here we show that in transcription factor Pitx3 gene mutant mice
      with a selective, severe DA loss in the dorsal striatum mimicking the DA
      denervation in late Parkinson's disease (PD), both the 5-HT innervation and the 5
      HT2AR mRNA expression were increased in the dorsal striatum. Functionally, while
      having no detectable motor effect in wild type mice, the 5-HT2R agonist 2,5
      dimethoxy-4-iodoamphetamine increased both the baseline and l-dopa-induced normal
      ambulatory and dyskinetic movements in Pitx3 mutant mice, whereas the selective 5
      HT2AR blocker volinanserin had the opposite effects. These results demonstrate
      that Pitx3 mutant mice are a convenient and valid mouse model to study the
      compensatory 5-HT upregulation following the loss of the nigrostriatal DA
      projection and that the upregulated 5-HT2AR function in the DA deficient dorsal
      striatum may enhance both normal and dyskinetic movements.

PMID- 23159835
TI  - Expression of immune-related genes in goldfish gills induced by Dactylogyrus
      intermedius infections.
AB  - Dactylogyrus intermedius, an oviparous monogenean parasite, is regarded as a
      devastating pathogen in freshwater aquaculture and ornamental fish trade, and
      accounts for significant economic losses worldwide. The study was undertaken to
      determine the differential expression of immune-related genes TNFalpha1,
      TNFalpha2, IL-1beta2, TGFbeta, iNOSa and iNOSb in goldfish gills during D.
      intermedius infection by real-time quantitative PCR. The results show that the
      expression of the pro-inflammatory cytokines (IL-1beta2, TNFalpha1 and TNFalpha2)
      and the anti-inflammatory cytokine (TGFbeta) were up-regulated at day 7 p.i.
      (post infection). The mRNA levels of these cytokines returned to normal levels or
      were down-regulated at day 21 p.i. In the cases of iNOSa and iNOSb, a significant
      up-regulation in iNOSa transcription levels were seen at day 14 p.i. while the
      expression of iNOSb gene showed a distinct up-regulation at day 7 p.i.
      Additionally, this study was conducted to investigate the expression of immune
      related genes in different degrees of goldfish experimentally infected with the
      monogenean D. intermedius. The results indicated that D. intermedius infection
      might regulate the fish immunity by showing differential expression levels of
      immune-related gene. The study confirms goldfish gill acts as an important source
      of inflammatory molecules, as well as an active modulator of local inflammation
      after initially infected with D. intermedius. Moreover, the results obtained in
      this study could be useful towards understanding the susceptibility of goldfish
      to D. intermedius and mechanisms involved in protection of goldfish to
      ectoparasitic infections.

PMID- 23159837
TI  - Endobronchial mascara brush.

PMID- 23159836
TI  - The transcriptional regulator lola is required for stem cell maintenance and germ
      cell differentiation in the Drosophila testis.
AB  - Stem cell behavior is regulated by extrinsic signals from specialized
      microenvironments, or niches, and intrinsic factors required for execution of
      context-appropriate responses to niche signals. Here we show that function of the
      transcriptional regulator longitudinals lacking (lola) is required cell
      autonomously for germline stem cell and somatic cyst stem cell maintenance in the
      Drosophila testis. In addition, lola is also required for proper execution of key
      developmental transitions during male germ cell differentiation, including the
      switch from transit amplifying progenitor to spermatocyte growth and
      differentiation, as well as meiotic cell cycle progression and spermiogenesis.
      Different lola isoforms, each having unique C-termini and zinc finger domains,
      may control different aspects of proliferation and differentiation in the male
      germline and somatic cyst stem cell lineages.

PMID- 23159838
TI  - Hypoglycaemia--more than skin deep.

PMID- 23159840
TI  - Does an interferon-gamma release assay change practice in possible latent
      tuberculosis?
AB  - BACKGROUND AND AIMS: Suspected latent tuberculosis infection (LTBI) is a common
      reason for referral to TB clinics. Interferon-gamma release assays (IGRAs) are
      more specific than tuberculin skin tests (TSTs) for diagnosing LTBI. The aim of
      this study is to determine if IGRA changes practice in the management of cases
      referred to a TB clinic for possible LTBI. DESIGN AND METHODS: A prospective
      study was performed over 29 months. All adult patients who had TST, CXR & IGRA
      were included. The original decision regarding TB chemoprophylaxis was made by TB
      team consensus, based on clinical history and TST. Cases were then analysed with
      the addition of IGRA to determine if this had altered management. An independent
      physician subsequently reviewed the cases. RESULTS: Of 204 patients studied, 68
      were immunocompromised. 120 patients had positive TSTs. Of these, 36 (30%) had a
      positive QFT and 84 (70%) had a negative QFT. Practice changed in 78 (65%) cases
      with positive TST, all avoiding TB chemoprophylaxis due to QFT. Of the
      immunocompromised patients, 17 (25%) underwent change of practice. No cases of
      active TB have developed. CONCLUSION: This study demonstrates a significant
      change of clinical practice due to IGRA use. Our findings support the NICE 2011
      recommendations.

PMID- 23159839
TI  - Direct-acting antiviral therapies for hepatitis C genotype 1 infection: a
      multiple treatment comparison meta-analysis.
AB  - BACKGROUND: New direct-acting antiviral agents for hepatitis C genotype 1
      infection, boceprevir and telaprevir, offer enhanced sustained virologic response
      (SVR) among both treatment-naive and treatment-experienced patients. AIM: To
      determine the relative efficacy of the new direct-acting antiviral agents by
      applying a multiple treatment comparison meta-analysis. DESIGN: We included
      published Phase II and III randomized controlled trials evaluating head-to-head
      comparisons between boceprevir, telaprevir, peg-interferon alpha-2a with
      ribavirin and peg-interferon alpha-2b with ribavirin in hepatitis C genotype 1
      patients. We applied Bayesian multiple treatment comparison meta-analysis.
      RESULTS: We included data from four boceprevir, three telaprevir and six peg
      interferon alpha-2a plus ribavirin vs. peg-interferon alpha-2b plus ribavirin
      randomized controlled trials. Both boceprevir and telaprevir offer statistically
      superior outcomes for SVR, relapse and discontinuation due to adverse events than
      either peg-interferons among both treatment-naive and treatment-experienced
      patients. Among treatment-naive patients, clinical outcomes were similar for
      boceprevir and telaprevir, for SVR [odds ratio (OR) 0.90, 95% credible interval
      (95% CrI) 0.41-1.91] and for relapse (OR 1.09, 95% CrI 0.19-4.84). Similarly,
      among treatment-experienced patients, clinical outcomes were similar for
      boceprevir and telaprevir and for SVR (OR 1.45, 95% CrI 0.70-3.08) and for
      relapse (OR 0.35, 95% CrI 0.13-1.02). For treatment-naive patients receiving
      standard-duration therapy, telaprevir yielded lower rates of anemia and
      neutropenia, but higher rates of rash and pruritus. For treatment-experience
      patients, all adverse event rates were higher with telaprevir. DISCUSSION:
      Boceprevir and telaprevir exhibit similar effects among hepatitis C genotype 1
      treatment-naive and treatment-experienced patients.

PMID- 23159841
TI  - Clinical application of the different cross-reactivities of anti-insulin
      antibodies to insulin lispro to evaluate endogenous insulin secretion.
AB  - BACKGROUND: Insulin analogs are often used to treat patients with diabetes. We
      evaluated the cross-reactivities of anti-insulin antibodies in two insulin
      immunoassay kits (Architect and ECLusys) against recombinant human insulin and
      insulin analogs, and measured insulin concentrations in the serum of the diabetic
      patients treated with only insulin lispro. METHODS: Ten-fold dilutions of
      recombinant human insulins and insulin analogs were measured using Architect and
      ECLusys kits. The serum samples of 4 type 2 diabetic patients at fasting, and
      several time points after breakfast (25 kcal/kg) following subcutaneous injection
      of insulin lispro were measured by Architect, ECLusys and LISPro RIA kit.
      RESULTS: The ECLusys kit could detect human insulin but not insulin analogs. The
      Architect kit detected human insulin and insulin analogs with similar recovery
      ratios. The difference in serum insulin concentrations measured by Architect and
      ECLusys assays reflected the concentration measured by LISPro insulin kit in the
      patients. The differences in the AUC between Architect and ECLusys assays were
      significantly correlated with the AUC for LISPro assay (p<0.01). CONCLUSIONS: By
      exploiting the different cross-reactivities of anti-insulin antibodies to insulin
      analogs, it may be possible to measure the endogenous and exogenous insulin
      concentrations in diabetic patients treated with insulin analogs.

PMID- 23159842
TI  - Hypercoagulability and cardiovascular disease in diabetic nephropathy.
AB  - Diabetic nephropathy is the leading cause of end stage renal disease (ESRD) and
      an important risk factor for cardiovascular disease. Recent studies have shown
      that increased plasma levels of Von Willebrand factor (VWF) and reduced plasma
      levels of enzyme ADAMTS13 are associated with diabetic nephropathy and an
      increased risk of developing cardiovascular disease, suggesting that these
      markers of hypercoagulability may contribute to an increased risk of
      cardiovascular disease in diabetic patients with impaired renal function.
      However, it is still not clear whether VWF and ADAMTS13 are only markers of
      cardiovascular events or whether they play an active role in the development of
      these events. It is also unclear how renal injury may affect ADAMTS13 levels,
      leading consequently to hypercoagulability. The association of diabetic
      nephropathy, atherosclerotic cardiovascular disease and these hypercoagulability
      markers is discussed in this review. Insights on the role that renal dysfunction
      and other possible mechanisms may have in ADAMTS13 metabolism, leading to reduced
      levels of this enzyme and increased hypercoagulability are also presented.

PMID- 23159843
TI  - Rapid detection of PML-RARA fusion gene by novel high-speed droplet-reverse
      transcriptase-polymerase chain reaction: possibility for molecular diagnosis
      without lagging behind the morphological analyses.
AB  - BACKGROUND: Acute promyelocytic leukemia (APL) is an aggressive disease requiring
      prompt diagnosis and treatment. Rapid detection of the PML-RARA fusion gene
      provides the molecular basis for a highly effective therapy with all-trans
      retinoic acid. We developed a rapid assay by novel droplet-reverse transcriptase
      polymerase chain reaction (droplet-RT-PCR) for the detection of the PML-RARA
      fusion gene in APL patients. METHODS: RNA was extracted from 7 samples obtained
      from 5 APL patients with the PML-RARA fusion gene confirmed by nested RT-PCR and
      fluorescence in situ hybridization. Using these 7 samples, we evaluated the
      reaction time and amplification efficiency of the droplet-RT-PCR. RESULTS: Using
      the droplet-RT-PCR, we could detect the PML-RARA fusion gene in all 7 samples.
      The reaction time for 50 cycles of droplet-RT-PCR was 27 min. The amplification
      by the droplet-RT-PCR assay was considered positive for the PML-RARA fusion gene
      in less than 22 min, at the point when the fluorescence exceeded the threshold
      level. CONCLUSIONS: Our novel droplet-RT-PCR assay is specific for the detection
      of the PML-RARA fusion gene and has a markedly reduced reaction time. Thus, the
      novel droplet-RT-PCR assay contributes to the rapid diagnosis of APL without
      lagging behind the morphological assessment.

PMID- 23159844
TI  - Is phosphoproteomics ready for clinical research?
AB  - BACKGROUND: For many diseases such as cancer where phosphorylation-dependent
      signaling is the foundation of disease onset and progression, single-gene testing
      and genomic profiling alone are not sufficient in providing most critical
      information. The reason for this is that in these activated pathways the
      signaling changes and drug resistance are often not directly correlated with
      changes in protein expression levels. In order to obtain the essential
      information needed to evaluate pathway activation or the effects of certain drugs
      and therapies on the molecular level, the analysis of changes in protein
      phosphorylation is critical. METHODS: Existing approaches do not differentiate
      clinical disease subtypes on the protein and signaling pathway level, and
      therefore hamper the predictive management of the disease and the selection of
      therapeutic targets. CONCLUSIONS: The mini-review examines the impact of emerging
      systems biology tools and the possibility of applying phosphoproteomics to
      clinical research.

PMID- 23159845
TI  - Ketoacidosis and trace amounts of isopropanol in a chronic alcoholic patient.
AB  - BACKGROUND: Alcohol ketoacidosis is a frequently missed diagnosis, but is well
      described in the literature. We present a case of ketoacidosis, likely alcohol
      ketoacidosis, in a 40 y-old chronic alcoholic patient. The detection of trace
      serum isopropanol prompted a discussion of alcohol ketoacidosis versus toxic
      isopropanol ingestion or a combination of both, including comparisons with
      citations in current literature. METHODS: The automated instruments used to
      analyze the patient's urine, blood, and serum samples are described. RESULTS: The
      initial impression was severe metabolic acidosis with an increased anion gap and
      normal serum glucose and whole blood lactate. Testing for potential toxic
      ingestions detected only increased serum acetone and trace serum isopropanol. A
      urinalysis positive for ketones and an increased serum beta-hydroxybutyrate
      concentration clenched the diagnosis of ketoacidosis. CONCLUSION: Ketoacidosis
      with an increased anion gap in the absence of hyperglycemia or glycosuria in a
      chronic alcoholic patient should prompt the evaluation for alcohol ketoacidosis.
      Trace serum isopropanol may be worrisome for a toxic ingestion, but this finding
      in severe ketoacidosis may be explained by the reversible action of the enzyme
      alcohol dehydrogenase. Markedly increased serum isopropanol with a low serum
      acetone:isopropanol ratio would be more indicative of a toxic isopropanol
      ingestion.

PMID- 23159846
TI  - Influence of indoor air conditions on radon concentration in a detached house.
AB  - Radon is released from soil and building materials and can accumulate in
      residential buildings. Breathing radon and radon progeny for extended periods
      hazardous to health and can lead to lung cancer. Indoor air conditions and
      ventilation systems strongly influence indoor radon concentrations. This paper
      focuses on effects of air change rate, indoor temperature and relative humidity
      on indoor radon concentrations in a one family detached house in Stockholm,
      Sweden. In this study a heat recovery ventilation system unit was used to control
      the ventilation rate and a continuous radon monitor (CRM) was used to measure
      radon levels. FLUENT, a computational fluid dynamics (CFD) software package was
      used to simulate radon entry into the building and air change rate, indoor
      temperature and relative humidity effects using a numerical approach. The results
      from analytical solution, measurements and numerical simulations showed that air
      change rate, indoor temperature and moisture had significant effects on indoor
      radon concentration. Increasing air change rate reduces radon level and for a
      specific air change rate (in this work Ach = 0.5) there was a range of
      temperature and relative humidity that minimized radon levels. In this case study
      minimum radon levels were obtained at temperatures between 20 and 22  degrees C
      and a relative humidity of 50-60%.

PMID- 23159847
TI  - New targeted therapies and other advances in the management of anaplastic thyroid
      cancer.
AB  - PURPOSE OF REVIEW: Anaplastic thyroid cancer is the most aggressive solid tumor
      known to humans. Even when found in a localized form, the prognosis is grave. For
      metastatic disease, there has been little effect on survival using traditional
      chemotherapy. RECENT FINDINGS: Over a five-decade interval, there has been little
      progress in the treatment of this malignancy. However, targeted agents represent
      a new mode of treatment, and some studies have shown encouraging preclinical
      results. Combretastatin has shown activity in phase 1 and phase II trials;
      although the registration phase III study failed to meet its accrual goals, it
      did appear to show some benefit, especially in younger patients. SUMMARY:
      Combinations of this compound and other targeted agents may prove to be a
      breakthrough in an otherwise untreatable cancer.

PMID- 23159848
TI  - p21WAF1 and tumourigenesis:  20 years after.
AB  - PURPOSE OF REVIEW: This review provides an overview of the structure, regulation
      and physiological functions of p21, the product of the cyclin-dependent kinase
      inhibitor 1A (CDKN1A) gene, with a focus on its dual role in promoting and
      repressing biological processes that are hallmarks of tumourigenesis. RECENT
      FINDINGS: Recent work has provided a better understanding of the molecular
      mechanisms of how oncogenic signalling pathways influence p21 expression. In
      response to cellular stimuli, p21 expression is tightly regulated at
      transcriptional and post-translational levels through mechanisms involving RNA
      stabilization, phosphorylation and ubiquitination. As a result, growing evidence
      reveals that several important tumour suppressor and oncogenic signalling
      pathways alter p21 expression to elicit their effects on cell cycle progression
      and survival. Thus, p21 expression can both promote and inhibit tumourigenic
      processes, depending on the cellular context. SUMMARY: Since its discovery, it
      has become increasingly clear that p21 can function as both a classical tumour
      suppressor and an oncogene. In order to effectively utilize p21 as a therapeutic
      target, it will be necessary to design therapeutic strategies that preferentially
      block the ability of p21 to promote senescence, stem cell renewal and cyclin/CDK
      activation, while leaving its tumour suppressive functions intact.

PMID- 23159849
TI  - Estrogen receptor alpha is a novel target of the Von Hippel-Lindau protein and is
      responsible for the proliferation of VHL-deficient cells under hypoxic
      conditions.
AB  - The Von Hippel-Lindau gene (VHL) is frequently deleted or mutated in human renal
      cell carcinoma (RCC) at the early stage. According to the well-established
      theory, pVHL acts as a tumor suppressor through its E3 ligase activity, which
      targets hypoxia-inducing factor-1alpha (HIF-1alpha). However, the elevated
      expression of HIF-1alpha did not promote cell proliferation, indicating that
      there would be another target, which could promote cell proliferation at the
      early cancer stage of RCC. In this study, we show that estrogen receptor-alpha
      (ER-alpha) is a novel proteasomal degradation target of the pVHL E3 ligase.
      Indeed, the overexpression of VHL suppresses exo- and endogenous ER-alpha
      expression, whereas si-pVHL can increase ER-alpha expression. The negative
      regulation of pVHL on ER-alpha expression is achieved by its E3 ligase activity.
      Thus, pVHL can promote the ER-alpha ubiquitinylation. In addition, we revealed
      that ER-alpha and HIF-1alpha are competitive substrates of pVHL. Thus, under
      normal conditions, ER-alpha overexpression can increase the transcription factor
      activity of HIF-1alpha. Under the hypoxic condition, where HIF-1alpha is not a
      suitable target of pVHL, ER-alpha is more rapidly degraded by pVHL. However, in
      VHL-deficient cells, the expression of ER-alpha and HIF-1alpha is retained, so
      that the hypoxic condition did not suppress cell proliferation obviously compared
      with cells that are expressing pVHL. Thus, blocking of ER-alpha using its
      inhibitor could suppress the proliferation of VHL-deficient cells as effectively
      as hypoxia-induced growth suppression. Considering our results, blocking of ER
      alpha signaling in VHL-deficient cancer cells would be beneficial for cancer
      suppression. Indeed, we showed the anti-proliferative effect of Faslodex in VHL
      deficient cells.

PMID- 23159850
TI  - On the connections between cancer stem cells and EMT.

PMID- 23159851
TI  - The deubiquitinating protein USP24 interacts with DDB2 and regulates DDB2
      stability.
AB  - Damage-specific DNA-binding protein 2 (DDB2) was first isolated as a subunit of
      the UV-DDB heterodimeric complex that is involved in DNA damage recognition in
      the nucleotide excision repair pathway (NER). DDB2 is required for efficient
      repair of CPDs in chromatin and is a component of the CRL4 (DDB2)  E3 ligase that
      targets XPC, histones and DDB2 itself for ubiquitination. In this study, a yeast
      two-hybrid screening of a human cDNA library was performed to identify potential
      DDB2 cellular partners. We identified a deubiquitinating enzyme, USP24, as a
      likely DDB2-interacting partner. Interaction between DDB2 and USP24 was confirmed
      by co-precipitation. Importantly, knockdown of USP24 in two human cell lines
      decreased the steady-state levels of DDB2, indicating that USP24-mediated DDB2
      deubiquitination prevents DDB2 degradation. In addition, we demonstrated that
      USP24 can cleave an ubiquitinated form of DDB2 in vitro. Taken together, our
      results suggest that the ubiquitin-specific protease USP24 is a novel regulator
      of DDB2 stability.

PMID- 23159852
TI  - Downregulation of Cdc6 and pre-replication complexes in response to methionine
      stress in breast cancer cells.
AB  - Methionine and homocysteine are metabolites in the transmethylation pathway
      leading to synthesis of the methyl-donor S-adenosylmethionine (SAM). Most cancer
      cells stop proliferating during methionine stress conditions, when methionine is
      replaced in the growth media by its immediate metabolic precursor homocysteine
      (Met-Hcy+). Non-transformed cells proliferate in Met-Hcy+ media, making the
      methionine metabolic requirement of cancer cells an attractive target for
      therapy, yet there is relatively little known about the molecular mechanisms
      governing the methionine stress response in cancer cells. To study this
      phenomenon in breast cancer cells, we selected methionine-independent-resistant
      cell lines derived from MDAMB468 breast cancer cells. Resistant cells grew
      normally in Met-Hcy+ media, whereas their parental MDAMB468 cells rapidly arrest
      in the G 1 phase. Remarkably, supplementing Met-Hcy+ growth media with S
      adenosylmethionine suppressed the cell proliferation defects, indicating that
      methionine stress is a consequence of SAM limitation rather than low amino acid
      concentrations. Accordingly, mTORC1 activity, the primary effector responding to
      amino acid limitation, remained high. However, we found that levels of the
      replication factor Cdc6 decreased and pre-replication complexes were destabilized
      in methionine-stressed MDAMB468 but not resistant cells. Our study characterizes
      metabolite requirements and cell cycle responses that occur during methionine
      stress in breast cancer cells and helps explain the metabolic uniqueness of
      cancer cells.

PMID- 23159853
TI  - Presence of a defect in karyokinesis during megakaryocyte endomitosis.
AB  - Megakaryocyte is the naturally polyploid cell that gives rise to platelets.
      Polyploidization occurs by endomitosis, a process corresponding to a late failure
      of cytokinesis with a backward movement of the daughter cells. Generally, a pure
      defect in cytokinesis produces a multinucleated cell, but megakaryocytes are
      characterized by a single polylobulated nucleus with a 2 (N)  ploidy. Here, we
      show the existence of a defect in karyokinesis during the endomitotic process.
      From late telophase until the reversal of cytokinesis, some dipolar
      mitosis/endomitosis and most multipolar endomitosis present a thin DNA link
      between the segregated chromosomes surrounded by an incomplete nuclear membrane
      formation, which implies that sister chromatid separation is not complete. This
      observation may explain why polyploid megakaryocytes display a single
      polylobulated nucleus along with an increase in ploidy.

PMID- 23159855
TI  - More tasks for Dna2 in S-phase.

PMID- 23159856
TI  - Transforming growth factor-beta: guardian of catabolic metabolism in carcinoma
      associated fibroblasts.

PMID- 23159857
TI  - Rapamycin in lipoproteins for enhanced delivery.

PMID- 23159854
TI  - Ectopic NGAL expression can alter sensitivity of breast cancer cells to EGFR, Bcl
      2, CaM-K inhibitors and the plant natural product berberine.
AB  - Neutrophil gelatinase-associated lipocalin (NGAL, a.k.a Lnc2) is a member of the
      lipocalin family and has diverse roles. NGAL can stabilize matrix
      metalloproteinase-9 from autodegradation. NGAL is considered as a siderocalin
      that is important in the transport of iron. NGAL expression has also been
      associated with certain neoplasias and is implicated in the metastasis of breast
      cancer. In a previous study, we examined whether ectopic NGAL expression would
      alter the sensitivity of breast epithelial, breast and colorectal cancer cells to
      the effects of the chemotherapeutic drug doxorubicin. While abundant NGAL
      expression was detected in all the cells infected with a retrovirus encoding
      NGAL, this expression did not alter the sensitivity of these cells to doxorubicin
      as compared with empty vector-transduced cells. We were also interested in
      determining the effects of ectopic NGAL expression on the sensitivity to small
      molecule inhibitors targeting key signaling molecules. Ectopic NGAL expression
      increased the sensitivity of MCF-7 breast cancer cells to EGFR, Bcl-2 and
      calmodulin kinase inhibitors as well as the natural plant product berberine.
      Furthermore, when suboptimal concentrations of certain inhibitors were combined
      with doxorubicin, a reduction in the doxorubicin IC 50 was frequently observed.
      An exception was observed when doxorubicin was combined with rapamycin, as
      doxorubicin suppressed the sensitivity of the NGAL-transduced MCF-7 cells to
      rapamycin when compared with the empty vector controls. In contrast, changes in
      the sensitivities of the NGAL-transduced HT-29 colorectal cancer cell line and
      the breast epithelial MCF-10A cell line were not detected compared with empty
      vector-transduced cells. Doxorubicin-resistant MCF-7/Dox (R)  cells were examined
      in these experiments as a control drug-resistant line; it displayed increased
      sensitivity to EGFR and Bcl-2 inhibitors compared with empty vector transduced
      MCF-7 cells. These results indicate that NGAL expression can alter the
      sensitivity of certain cancer cells to small-molecule inhibitors, suggesting that
      patients whose tumors exhibit elevated NGAL expression or have become drug
      resistant may display altered responses to certain small-molecule inhibitors.

PMID- 23159859
TI  - Lasonolide A, a potent and reversible inducer of chromosome condensation.
AB  - Lasonolide A (LSA) is a natural product with high and selective cytotoxicity
      against mesenchymal cancer cells, including leukemia, melanomas and
      glioblastomas. Here, we reveal that LSA induces rapid and reversible premature
      chromosome condensation (PCC) associated with cell detachment, plasma membrane
      smoothening and actin reorganization. PCC is induced at all phases of the cell
      cycle in proliferative cells as well as in circulating human lymphocytes in G 0.
      It is independent of Cdk1 signaling, associated with cyclin B downregulation and
      induced in cells at LSA concentrations that are three orders of magnitude lower
      than those required to block phosphatases 1 and 2A in vitro. At the epigenetic
      level, LSA-induced PCC is coupled with histone H3 and H1 hyperphosphorylation and
      deacetylation. Treatment with SAHA reduced LSA-induced PCC, implicating histone
      deacetylation as one of the PCC effector mechanisms. In addition, PCC is coupled
      with topoisomerase II (Top2) and Aurora A hyperphosphorylation and activation.
      Inhibition of Top2 or Aurora A partially blocked LSA-induced PCC. Our findings
      demonstrate the profound epigenetic alterations induced by LSA and the potential
      of LSA as a new cytogenetic tool. Based on the unique cellular effects of LSA,
      further studies are warranted to uncover the cellular target of lasonolide A
      ("TOL").

PMID- 23159858
TI  - Nek9 regulates spindle organization and cell cycle progression during mouse
      oocyte meiosis and its location in early embryo mitosis.
AB  - Nek9 (also known as Nercc1), a member of the NIMA (never in mitosis A) family of
      protein kinases, regulates spindle formation, chromosome alignment and
      segregation in mitosis. Here, we showed that Nek9 protein was expressed from
      germinal vesicle (GV) to metaphase II (MII) stages in mouse oocytes with no
      detectable changes. Confocal microscopy identified that Nek9 was localized to the
      spindle poles at the metaphase stages and associated with the midbody at anaphase
      or telophase stage in both meiotic oocytes and the first mitotic embyros.
      Depletion of Nek9 by specific morpholino injection resulted in severely defective
      spindles and misaligned chromosomes with significant pro-MI/MI arrest and failure
      of first polar body (PB1) extrusion. Knockdown of Nek9 also impaired the spindle
      pole localization of gamma-tubulin and resulted in retention of the spindle
      assembly checkpoint protein Bub3 at the kinetochores even after 10 h of culture.
      Live-cell imaging analysis also confirmed that knockdown of Nek9 resulted in
      oocyte arrest at the pro-MI/MI stage with abnormal spindles, misaligned
      chromosomes and failed polar body emission. Taken together, our results suggest
      that Nek9 may act as a MTOC-associated protein regulating microtubule nucleation,
      spindle organization and, thus, cell cycle progression during mouse oocyte
      meiotic maturation, fertilization and early embryo cleavage.

PMID- 23159860
TI  - Multiplying madly: deacetylases take charge of centrosome duplication and
      amplification.

PMID- 23159861
TI  - Unfolding tyrosine kinase inhibitor sensitivity in chronic myeloid leukemia.

PMID- 23159864
TI  - Special issue: the emotional brain and its relation to psychopathology.

PMID- 23159863
TI  - First tier modeling of consumer dermal exposure to substances in consumer
      articles under REACH: a quantitative evaluation of the ECETOC TRA for consumers
      tool.
AB  - The demonstration of safe use of chemicals in consumer products, as required
      under REACH, is proposed to follow a tiered process. In the first tier, simple
      conservative methods and assumptions should be made to quickly verify whether
      risks for a particular use are expected. The ECETOC TRA Consumer Exposure Tool
      was developed to assist in first tier risk assessments for substances in consumer
      products. The ECETOC TRA is not a prioritization tool, but is meant as a first
      screening. Therefore, the exposure assessment needs to cover all
      products/articles in a specific category. For the assessment of the dermal
      exposure for substances in articles, ECETOC TRA uses the concept of a 'contact
      layer', a hypothetical layer that limits the exposure to a substance contained in
      the product. For each product/article category, ECETOC TRA proposes default
      values for the thickness of this contact layer. As relevant experimental exposure
      data is currently lacking, default values are based on expert judgment alone. In
      this paper it is verified whether this concept meets the requirement of being a
      conservative exposure evaluation method. This is done by confronting the ECETOC
      TRA expert judgment based predictions with a mechanistic emission model, based on
      the well established theory of diffusion of substances in materials. Diffusion
      models have been applied and tested in many applications of emission modeling.
      Experimentally determined input data for a number of material and substance
      combinations are available. The estimated emissions provide information on the
      range of emissions that could occur in reality. First tier tools such as ECETOC
      TRA tool are required to cover all products/articles in a category and to provide
      estimates that are at least as high as is expected on the basis of current
      scientific knowledge. Since this was not the case, it is concluded that the
      ECETOC TRA does not provide a proper conservative estimation method for the
      dermal exposure to articles. An alternative method was proposed.

PMID- 23159865
TI  - Prefrontal/accumbal catecholamine system processes emotionally driven attribution
      of motivational salience.
AB  - Motivational salience regulates the strength of goal seeking, the amount of risk
      taken, and the energy invested, from mild to extreme. Emotional experiences
      promote highly persistent memories. Although this phenomenon is adaptive in
      normal conditions, experiences with extremely high levels of motivational
      salience can promote the development of memories, resulting in maladaptive
      outcomes such as compulsive seeking or avoidance. We have offered evidence that
      prefrontal cortical norepinephrine transmission is a necessary condition for
      motivational salience attribution to highly salient stimuli through modulation of
      dopamine in the nucleus accumbens, a brain area involved in motivated behaviors.
      Moreover, the prefrontal-accumbal catecholamine system determines approach or
      avoidance responses to both reward- and aversion-related stimuli only when the
      salience of the unconditioned stimulus is high enough to induce sustained
      catecholamine activation, thus affirming that this system processes motivational
      salience attribution selectively to highly salient events. This system, when
      activated by highly salient stimuli, is likely to lead to motivational and neural
      processes that trigger mechanisms causing aberrant motivational salience
      attribution and to engage other frontal-subcortical systems, resulting in
      compulsion-driven behavioral disorders.

PMID- 23159862
TI  - Tissue-specific expression of p73 C-terminal isoforms in mice.
AB  - p73 is a p53 family transcription factor. Due to the presence in the 5' flanking
      region of two promoters, there are two N-terminal variants, TAp73, which retains
      a fully active transactivation domain (TA), and DeltaNp73, in which the N
      terminus is truncated. In addition, extensive 3' splicing gives rise to at least
      seven distinctive isoforms; TAp73-selective knockout highlights its role as a
      regulator of cell death, senescence and tumor suppressor. DeltaNp73-selective
      knockout, on the other hand, highlights anti-apoptotic function of DeltaNp73 and
      its involvement in DNA damage response. In this work, we investigated the
      expression pattern of murine p73 C-terminal isoforms. By using a RT-PCR approach,
      we were able to detect mRNAs of all the C-terminal isoforms described in humans.
      We characterized their in vivo expression profile in mouse organs and in
      different mouse developmental stages. Finally, we investigated p73 C-terminal
      expression profile following DNA damage, ex vivo after primary cultures treatment
      and in vivo after systemic administration of cytotoxic compounds. Overall, our
      study first elucidates spatio-temporal expression of mouse p73 isoforms and
      provides novel insights on their expression-switch under triggered conditions.

PMID- 23159866
TI  - Learning to cope with stress: psychobiological mechanisms of stress resilience.
AB  - Stress is the main non-genetic source of psychopathology. Therefore, the
      identification of neurobiological bases of resilience, the resistance to
      pathological outcomes of stress, is a most relevant topic of research. It is an
      accepted view that resilient individuals are those who do not develop
      helplessness, or other depression-like phenotypes, following a history of stress.
      In the present review, we discuss the phenotypic differences between mice of the
      inbred C57BL/6J and DBA/2J strains that could be associated with the strain
      specific resistance to helplessness observable in DBA/2J mice. The reviewed
      results support the hypothesis that resilience to stress-promoted helplessness
      develops through interactions between a specific genetic makeup and a history of
      stress, and is associated with an active coping style, a bias toward the use of
      stimulus-response learning, and specific adaptive changes of mesoaccumbens
      dopamine transmission under stress. Finally, evidence that compulsivity
      represents a side effect of the neuroadaptive processes fostering resistance to
      develop depressive-like phenotypes under stress is discussed.

PMID- 23159867
TI  - Maternal exposure to low levels of corticosterone during lactation increases
      social play behavior in rat adolescent offspring.
AB  - Although costly in energy and time, social play is present and evolutionarily
      conserved in nearly all young mammals. Ontogenetic factors responsible for this
      particular form of supposed rewarding behavior are incompletely understood. Here,
      we have focused our attention on maternal glucocorticoid hormone. We used a model
      in which neonate rats are fed by mothers in which drinking water has been
      supplemented with 0.2 mg/ml corticosterone. The control groups were lactated by
      water-drinking mothers. Both male and female adolescent offspring of
      corticosterone (CORT) supplemented dams (CORT-nursed) showed an increase in
      social play behavior (i.e., pinning, pouncing, wrestling/boxing and social
      exploration) when compared to controls. No differences were observed between CORT
      nursed progeny of both sexes and controls in the exploration of the arena during
      the social encounter. Finally, no differences were found in CORT plasma levels in
      basal conditions and following a social play session in both male and female CORT
      nursed rats. These results indicate that variations in the maternal
      glucocorticoid status are able, directly or indirectly, to influence social play
      behavior in the offspring, although there is no direct relationship between the
      level of social play behavior and the intensity of adrenocortical activation.

PMID- 23159868
TI  - The role of setting for ketamine abuse: clinical and preclinical evidence.
AB  - Drug abuse is often seen as a unitary phenomenon, partly as a result of the
      discovery over the past three decades of shared mechanisms of action for
      addictive substances. Yet the pattern of drug taking is often very different from
      drug to drug. This is particularly evident in the case of 'club drugs', such as
      ketamine. Although the number of ketamine abusers is relatively small in the
      general population, it is quite substantial in some settings. In particular,
      ketamine abuse is almost exclusively limited to clubs and large music parties,
      which suggests a major role of context in modulating the reward effects of this
      drug. This review focuses on recent preclinical and clinical findings, including
      previously unpublished data, that provide evidence that, even under controlled
      conditions, ketamine reward is a function of the setting of drug taking.

PMID- 23159869
TI  - Assessment of brain oxygenation in term and preterm neonates using near infrared
      spectroscopy.
AB  - PURPOSE: The aim of this study was to determine brain oxygenation in full-term
      and preterm neonates using near infrared spectroscopy. MATERIAL AND METHODS: A
      total of 88 full-term and preterm newborn infants without hypoxic-ischaemic
      disorders admitted to the NICU were examined using NIRS on the first day of life
      and on day 28 of life. Additional measurements were taken at the end of the first
      week of life in the premature neonates group. Measurements of oxyhaemoglobin
      (HbO2), deoxyhaemoglobin (Hb), total haemoglobin (HbT) concentration and tissue
      oxygen saturation (Ox) were performed in 5 brain regions. Right and left frontal
      areas, the occipital area and right and left temporal areas were measured.
      RESULTS: In full-term healthy neonates a marked decrease in HbO, Hb and HbT
      values was observed on day 28 of life in all brain regions except the occipital
      area. In the neonatal period the greatest changes in brain oxygenation occurred
      in the right and left frontal regions of the brain. In preterm neonates constant
      values of HbO2 and Ox were observed in the first 28 days of life. In preterm
      newborn infants, as well as in full term newborn infants, similar Ox and HbO2
      values were obtained on day 28 of life. CONCLUSIONS: NIRS is a safe method and
      can be used to evaluate brain oxygenation in newborn infants. The results of
      these measurements are in accordance with changes in brain oxygenation in the
      first month of life, which are predicated on the basis of the neonate's
      physiology.

PMID- 23159870
TI  - Estimating photon interaction coefficients from single energy x-ray CT.
AB  - Single energy x-ray analysis is explored in the context of computed tomography
      (CT), whereby Hounsfield numbers (HN) are used to estimate electron density N(e)
      and parameters that describe composition. We examine measurements with tissue
      substitute materials and theoretical HN for a broad range of tissues. Results are
      combined with parametric models for the x-ray linear attenuation coefficient MU
      and energy absorption coefficient MU(en) to predict values at energies 10 keV to
      20 MeV. At photon energies employed for CT, the fractional contribution to MU
      from composition is 0.1-0.4 for soft tissues to bone respectively, and is
      responsible for strong correlations between HN and N(e). The atomic density of
      tissues excluding lung is near constant allowing the models to be re-expressed as
      a function of N(e) alone. The transformed model is subjected to propagation of
      error analysis and results are presented as the ratio of uncertainties for MU or
      MU(en) to those for N(e). For soft tissues to bone the ratios are as follows: at
      photon energies 20-100 keV the ratio is 5.0-2.0, at intermediate energies it is
      unity and increases above 4 MeV to reach 1.5-2.0 at 20 MeV. Results are discussed
      in the context of attenuation correction and dosimetry calculations for the same
      range of photon energies.

PMID- 23159872
TI  - Characterization of myosin light chain gene up-regulated in the large yellow
      croaker immunity by interaction with RanGTPase.
AB  - RanGTPases are highly conserved in eukaryotes from yeast to human and have been
      implicated in many aspects of nuclear structure and function. In our previous
      study, it was revealed that the RanGTPase was up-regulated in large yellow
      croaker challenged by pathogen. However, the mechanism of RanGTPase in immunity
      remains unclear. In this investigation, on the basis of protein interaction, it
      was found that RanGTPase interacted with myosin light chain (designated as
      LycMLC), a crucial protein in the process of phagocytosis. Furthermore, it was
      found and characterized in this marine fish for the first time. The full-length
      cDNA of LycMLC was 771bp, including a 5'-terminal untranslated region (UTR) of
      36bp, 3'-terminal UTR of 279bp and an open reading frame (ORF) of 456bp encoding
      a polypeptide of 151 amino acids. RT-PCR analysis indicated that LycMLC gene was
      constitutively expressed in the 9 tissues examined, including kidney, liver,
      gill, muscle, spleen, skin, heart, intestine and blood. The result of
      quantitative real-time PCR analysis revealed the highest expression in muscle and
      the weakest expression in skin. Time course analysis showed that LycMLC
      expression was obviously up-regulated in blood after immunization with either
      poly I:C or formalin-inactive Gram-negative bacteria Vibrio parahaemolyticus. It
      indicated that the highest expression was 4.5 times (at 24h) as much as that in
      the control (P<0.05) challenged by poly I:C and 5.0 times (at 24h) challenged by
      bacteria. These results suggested that LycMLC might play an important role in
      large yellow croaker defense against the pathogen infection. Therefore our study
      revealed a novel pathway concerning immunity of RanGTPase by the direct
      interaction with the cytoskeleton protein, which would help to better understand
      the molecular events in immune response against pathogen infection in fish.

PMID- 23159873
TI  - A new ATP7B gene mutation with severe condition in two unrelated Iranian families
      with Wilson disease.
AB  - Wilson disease is associated with a defect in copper metabolism and caused by
      different mutations in ATP7B gene. The aim of this study was to determine
      mutation frequency of ATP7B exons 8 and 14 in Wilson disease patients from the
      south of Iran. The exons 8 and 14 of ATP7B gene were analyzed in 65 unrelated
      Wilson disease patients by Denaturing High Performance Liquid Chromatography, and
      samples with abnormal peak profile were selected for direct DNA sequencing. Seven
      out of 65 (10.8%) patients had mutations at exon 14, including c.3061-1G>A in
      four and c.3207C>A in three patients. In addition, four different mutations were
      identified at exon 8 of six patients (9.2%). Three of these mutations have been
      previously reported, including c.2304delC in two patients, c.2293G>A and 2304dupC
      each in one patient. Furthermore, a novel mutation, c.2335T>G (p.Trp779Gly), was
      identified in two unrelated patients. The patients with this novel mutation
      demonstrated severe neuropsychiatric condition. All together, 13 out of 65 (20%)
      patients had mutations within exons 8 and 14. We also identified a lower
      frequency of the most common mutations of exons 8 and 14 in the southern Iranian
      population.

PMID- 23159874
TI  - Pro-inflammatory cytokine gene polymorphisms and threat for coronary heart
      disease in a North Indian Agrawal population.
AB  - The association of IFN-gamma (+874 A/T; rs2430561), TNF-alpha (-308 G/A;
      rs1800629) and TNF-beta (+252 A/G; rs909253) with Coronary Heart Disease (CHD)
      has not been rigorously tested in Indian population. In the present study we
      sought to examine the role of these cytokines in the causation of CHD and their
      association with conventional CHD risk factors. A total of 138 case and 187
      unrelated healthy controls aged 35 to 80years, matched on ethnicity and geography
      were collected from North Indian Agrawal population. Single nucleotide
      polymorphisms at the promoter TNF-alpha -308 G/A and the intronic IFN-gamma +874
      A/T were analyzed by allele-specific PCR, and the intronic TNF-beta +252 A/G was
      analyzed by RFLP. Of the three selected polymorphisms, genotypic distribution of
      IFN-gamma +874 A/T and TNF-beta +252 A/G polymorphisms was significantly
      different between patients and controls in the present study. OR revealed
      statistically significant risk for CHD with respect to IFN-gamma +874 T allele,
      whereas OR for TNF-beta +252 A/G showed three fold risk in homozygous condition
      though not significant. No such trend could be observed for TNF-alpha -308 G/A
      polymorphism. Multivariate logistic regression after adjusting for all the
      confounders showed significant risk for CHD with the genotypes and genotypic
      combinations of all the three markers (albeit not significant with TNF-alpha).
      Increased risk for CHD was likely to be associated with interaction of IFN-gamma
      with diastolic hypertension, TNF-alpha with diabetes and BMI, and TNF-beta with
      serum triglyceride and very low density lipoprotein (VLDL) levels. The results
      suggest that these selected cytokine polymorphisms could possibly serve as
      potential bio-markers for CHD in conjunction with specific conventional risk
      factors.

PMID- 23159876
TI  - Osterix induces Col1a1 gene expression through binding to Sp1 sites in the bone
      enhancer and proximal promoter regions.
AB  - Bone-specific transcription factors promote differentiation of mesenchymal
      precursors toward the osteoblastic cell phenotype. Among them, Runx2 and Osterix
      have been widely accepted as master osteogenic factors, since neither Runx2 nor
      Osterix null mice form mature osteoblasts. Recruitment of Osterix to a number of
      promoters of bone-specific genes has been shown. However, little is known about
      the functional interactions between Osterix and the Col1a1 promoter. In this
      study we determined in several mesenchymal and osteoblastic cell types that
      either BMP-2 or Osterix overexpression increased Col1a1 transcription. We
      identified consensus Sp1 sequences, located in the proximal promoter and in the
      bone-enhancer, as Osterix binding regions in the Col1a1 promoter in vitro and in
      vivo. Furthermore, we show that p38 or Erk MAPK signaling is required for maximal
      transcriptional effects on Col1a1 expression. Runx2 has been shown to activate
      Col1a1 expression through binding to sites which are located close to the Sp1
      sites where Osterix binds. Our data show that overexpression of Runx2 and Osterix
      leads to a cooperative effect on the expression of the Col1a1 endogenous gene and
      its promoter reporter construct. These effects mainly affect the long isoform of
      Osterix which suggest that the two Osterix isoforms might display some
      differential effects on the transactivation of bone-specific genes.

PMID- 23159877
TI  - Electrophysiological correlates of looking at paintings and its association with
      art expertise.
AB  - This study investigated the electrocortical correlates of art expertise, as
      defined by a newly developed, content-valid and internally consistent 23-item art
      expertise questionnaire in N=27 participants that varied in their degree of art
      expertise. Participants viewed each 50 paintings, filtering-distorted versions of
      these paintings and plain colour stimuli under free-viewing conditions whilst the
      EEG was recorded from 64 channels. Results revealed P3b-/LPC-like bilateral
      posterior event-related potentials (ERP) that were larger over the right
      hemisphere than over the left hemisphere. Art expertise correlated negatively
      with the amplitude of the ERP responses to paintings and control stimuli. We
      conclude that art expertise is associated with reduced ERP responses to visual
      stimuli in general that can be considered to reflect increased neural efficiency
      due to extensive practice in the contemplation of visual art.

PMID- 23159875
TI  - Rate dependent effects of acute nicotine on risk taking in young adults are not
      related to ADHD diagnosis.
AB  - Beneficial effects of nicotine on cognition and behavioral control are
      hypothesized to relate to the high rates of cigarette smoking in Attention
      Deficit/Hyperactivity Disorder (ADHD). Given that ADHD is associated with both
      impulsivity and elevated risk taking, we hypothesized that nicotine modulates
      risk taking, as it does impulsivity. 26 non-smoking young adults (15 controls
      with normal impulsivity and 11 ADHD with high impulsivity) received 7 mg
      transdermal nicotine, 20mg oral mecamylamine, and placebo on separate days,
      followed by the Balloon Analog Risk Task (BART). Statistical analyses found no
      group differences in baseline risk taking. Reexamination of the data using a
      median split on baseline risk taking, to create high (HRT) and low (LRT) risk
      taking groups, revealed significant effects of nicotinic drugs that differed by
      group. Nicotine reduced risk taking in HRT and mecamylamine increased risk taking
      in LRT. This finding supports the hypothesis that nicotinic receptor function
      modulates risk taking broadly, beyond those with ADHD, and is consistent with
      rate dependent cholinergic modulation of other cognitive functions. Further, the
      results demonstrate that high impulsivity is separable from high risk taking in
      young adults with ADHD, supporting the utility of these differential behavioral
      phenotypes for neurobiological studies.

PMID- 23159879
TI  - Large-scale screening using familial dysautonomia induced pluripotent stem cells
      identifies compounds that rescue IKBKAP expression.
AB  - Patient-specific induced pluripotent stem cells (iPSCs) represent a novel system
      for modeling human genetic disease and could provide a source of cells for large
      scale drug-discovery screens. Here we demonstrate the feasibility of performing a
      primary screen in neural crest precursors derived from iPSCs that were generated
      from individuals with familial dysautonomia (FD), a rare, fatal genetic disorder
      affecting neural crest lineages. We tested 6,912 small-molecule compounds and
      characterized eight that rescued expression of IKBKAP, the gene responsible for
      FD. One of the hits, SKF-86466, was found to induce IKBKAP transcription through
      modulation of intracellular cAMP levels and PKA-dependent CREB phosphorylation.
      SKF-86466 also rescued IKAP protein expression and the disease-specific loss of
      autonomic neuronal marker expression. Our data implicate alpha-2 adrenergic
      receptor activity in regulating IKBKAP expression and demonstrate that small
      molecule discovery using an iPSC-based disease model can identify candidate drugs
      for potential therapeutic intervention.

PMID- 23159880
TI  - A bacterial glycosidase enables mannose-6-phosphate modification and improved
      cellular uptake of yeast-produced recombinant human lysosomal enzymes.
AB  - Lysosomal storage diseases are treated with human lysosomal enzymes produced in
      mammalian cells. Such enzyme therapeutics contain relatively low levels of
      mannose-6-phosphate, which is required to target them to the lysosomes of patient
      cells. Here we describe a method for increasing mannose-6-phosphate modification
      of lysosomal enzymes produced in yeast. We identified a glycosidase from C.
      cellulans that 'uncaps' N-glycans modified by yeast-type mannose-Pi-6-mannose to
      generate mammalian-type N-glycans with a mannose-6-phosphate substitution.
      Determination of the crystal structure of this glycosidase provided insight into
      its substrate specificity. We used this uncapping enzyme together with alpha
      mannosidase to produce in yeast a form of the Pompe disease enzyme alpha
      glucosidase rich in mannose-6-phosphate. Compared with the currently used
      therapeutic version, this form of alpha-glucosidase was more efficiently taken up
      by fibroblasts from Pompe disease patients, and it more effectively reduced
      cardiac muscular glycogen storage in a mouse model of the disease.

PMID- 23159881
TI  - Microparticles bearing encephalitogenic peptides induce T-cell tolerance and
      ameliorate experimental autoimmune encephalomyelitis.
AB  - Aberrant T-cell activation underlies many autoimmune disorders, yet most attempts
      to induce T-cell tolerance have failed. Building on previous strategies for
      tolerance induction that exploited natural mechanisms for clearing apoptotic
      debris, we show that antigen-decorated microparticles (500-nm diameter) induce
      long-term T-cell tolerance in mice with relapsing experimental autoimmune
      encephalomyelitis. Specifically, intravenous infusion of either polystyrene or
      biodegradable poly(lactide-co-glycolide) microparticles bearing encephalitogenic
      peptides prevents the onset and modifies the course of the disease. These
      beneficial effects require microparticle uptake by marginal zone macrophages
      expressing the scavenger receptor MARCO and are mediated in part by the activity
      of regulatory T cells, abortive T-cell activation and T-cell anergy. Together
      these data highlight the potential for using microparticles to target natural
      apoptotic clearance pathways to inactivate pathogenic T cells and halt the
      disease process in autoimmunity.

PMID- 23159882
TI  - Protective efficacy of in vitro synthesized, specific mRNA vaccines against
      influenza A virus infection.
AB  - Despite substantial improvements, influenza vaccine production-and availability
      remain suboptimal. Influenza vaccines based on mRNA may offer a solution as
      sequence-matched, clinical-grade material could be produced reliably and rapidly
      in a scalable process, allowing quick response to the emergence of pandemic
      strains. Here we show that mRNA vaccines induce balanced, long-lived and
      protective immunity to influenza A virus infections in even very young and very
      old mice and that the vaccine remains protective upon thermal stress. This
      vaccine format elicits B and T cell-dependent protection and targets multiple
      antigens, including the highly conserved viral nucleoprotein, indicating its
      usefulness as a cross-protective vaccine. In ferrets and pigs, mRNA vaccines
      induce immunological correlates of protection and protective effects similar to
      those of a licensed influenza vaccine in pigs. Thus, mRNA vaccines could address
      substantial medical need in the area of influenza prophylaxis and the broader
      realm of anti-infective vaccinology.

PMID- 23159883
TI  - Modulation of cholinergic pathways and inflammatory mediators in blast-induced
      traumatic brain injury.
AB  - Cholinergic activity has been recognized as a major regulatory component of
      stress responses after traumatic brain injury (TBI). Centrally acting
      acetylcholinesterase (AChE) inhibitors are also being considered as potential
      therapeutic candidates against TBI mediated cognitive impairments. We have
      evaluated the expression of molecules involved in cholinergic and inflammatory
      pathways in various regions of brain after repeated blast exposures in mice.
      Isoflurane anesthetized C57BL/6J mice were restrained and placed in a prone
      position transverse to the direction of the shockwaves and exposed to three 20.6
      psi blast overpressures with 1-30 min intervals. Brains were collected at the 6h
      time point after the last blast exposure and subjected to cDNA microarray and
      microRNA analysis. cDNA microarray analysis showed significant changes in the
      expression of cholinergic (muscarinic and nicotinic) and gammaaminobutyric acid
      and glutamate receptors in the midbrain region along with significant changes in
      multiple genes involved in inflammatory pathways in various regions of the brain.
      MicroRNA analysis of cerebellum revealed differential expression of miR-132 and
      183, which are linked to cholinergic anti-inflammatory signaling, after blast
      exposure. Changes in the expression of myeloperoxidase in the cerebellum were
      confirmed by Western blotting. These results indicate that early pathologic
      progression of blast TBI involves dysregulation of cholinergic and inflammatory
      pathways related genes. Acute changes in molecules involved in the modulation of
      cholinergic and inflammatory pathways after blast TBI can cause long-term central
      and peripheral pathophysiological changes.

PMID- 23159884
TI  - Human paraoxonase double mutants hydrolyze V and G class organophosphorus nerve
      agents.
AB  - Variants of human paraoxonase 1 (PON1) are being developed as catalytic
      bioscavengers for the organophosphorus chemical warfare agents (OP). It is
      preferable that the new PON1 variants have broad spectrum hydrolase activities to
      hydrolyze both G- and V-class OPs. H115W PON1 has shown improvements over wild
      type PON1 in its capacity to hydrolyze some OP compounds. We improved upon these
      activities either by substituting a tryptophan (F347W) near the putative active
      site residues for enhanced substrate binding or by reducing a bulky group (Y71A)
      at the periphery of the putative enzyme active site. When compared to H115W
      alone, we found that H115W/Y71A and H115W/F347W maintained VX catalytic
      efficiency but showed mixed results for the capacity to hydrolyze paraoxon.
      Testing our double mutants against racemic sarin, we observed reduced values of
      K(M) for H115W/F347W that modestly improved catalytic efficiency over wild type
      and H115W. Contrary to previous reports, we show that H115W can hydrolyze soman,
      and the double mutant H115W/Y71A is nearly 4-fold more efficient than H115W for
      paraoxon hydrolysis. We also observed modest stereoselectivity for hydrolysis of
      the P(-) stereoisomer of tabun by H115W/F347W. These data demonstrate
      enhancements made in PON1 for the purpose of developing an improved catalytic
      bioscavenger to protect cholinesterase against chemical warfare agents.

PMID- 23159886
TI  - Biochemical and molecular mechanisms of N-acetyl cysteine and silymarin-mediated
      protection against maneb- and paraquat-induced hepatotoxicity in rats.
AB  - Oxidative stress is one of the major players in the pathogenesis of maneb (MB)
      and paraquat (PQ)-induced disorders. N-acetyl cysteine (NAC), a glutathione (GSH)
      precursor and silymarin (SIL), a naturally occurring antioxidant, encounter
      oxidative stress-mediated cellular damage. The present study was aimed to
      investigate the effects of NAC and SIL against MB and/or PQ-induced
      hepatotoxicity in rats. The levels of hepatotoxicity markers - alanine
      aminotransaminase (ALT), aspartate aminotransaminase (AST) and total bilirubin,
      histological changes, oxidative stress indices, phase I and phase II xenobiotic
      metabolizing enzymes - cytochrome P450 (CYP) and glutathione S-transferase (GST)
      and pro-inflammatory molecules - inducible nitric oxide synthase (iNOS), tumor
      necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) were measured
      in animals treated with MB and/or PQ in the presence or absence of NAC and SIL.
      MB and/or PQ augmented ALT, AST, total bilirubin, lipid peroxidation and nitrite
      contents and catalytic activities of superoxide dismutase and glutathione
      peroxidase however, the GSH content was attenuated. NAC and SIL restored the
      above-mentioned alterations towards basal levels but the restorations were more
      pronounced in SIL treated groups. Similarly, MB and/or PQ-mediated
      histopathological symptoms and changes in the catalytic activities/expressions of
      CYP1A2, CYP2E1, iNOS, TNF-alpha, and IL-1beta were alleviated by NAC and SIL.
      Conversely, MB and/or PQ-induced GSTA4-4 expression/activity was further
      increased by NAC/SIL and glutathione reductase activity was also increased. The
      results obtained thus suggest that NAC and SIL protect MB and/or PQ-induced
      hepatotoxicity by reducing oxidative stress, inflammation and by modulating
      xenobitic metabolizing machinery and SIL seems to be more effective.

PMID- 23159887
TI  - Expression of cAMP-responsive element binding proteins (CREBs) in fast- and slow
      twitch muscles: a signaling pathway to account for the synaptic expression of
      collagen-tailed subunit (ColQ) of acetylcholinesterase at the rat neuromuscular
      junction.
AB  - The gene encoding the collagen-tailed subunit (ColQ) of acetylcholinesterase
      (AChE) contains two distinct promoters that drive the production of two ColQ
      mRNAs, ColQ-1 and ColQ-1a, in slow- and fast-twitch muscles, respectively. ColQ
      1a is expressed at the neuromuscular junction (NMJ) in fast-twitch muscle, and
      this expression depends on trophic factors supplied by motor neurons signaling
      via a cAMP-dependent pathway in muscle. To further elucidate the molecular basis
      of ColQ-1a's synaptic expression, here we investigated the expression and
      localization of cAMP-responsive element binding protein (CREB) at the synaptic
      and extra-synaptic regions of fast- and slow-twitch muscles from adult rats. The
      total amount of active, phosphorylated CREB (P-CREB) present in slow-twitch
      soleus muscle was higher than that in fast-twitch tibialis muscle, but P-CREB was
      predominantly expressed in the fast-twitch muscle at NMJs. In contrast, P-CREB
      was detected in both synaptic and extra-synaptic regions of slow-twitch muscle.
      These results reveal, for the first time, the differential distribution of P-CREB
      in fast- and slow-twitch muscles, which might support the crucial role of cAMP
      dependent signaling in controlling the synapse-specific expression of ColQ-1a in
      fast-twitch muscles.

PMID- 23159885
TI  - Aldehyde dehydrogenases: from eye crystallins to metabolic disease and cancer
      stem cells.
AB  - The aldehyde dehydrogenase (ALDH) superfamily is composed of nicotinamide adenine
      dinucleotide (phosphate) (NAD(P)(+))-dependent enzymes that catalyze the
      oxidation of aldehydes to their corresponding carboxylic acids. To date, 24 ALDH
      gene families have been identified in the eukaryotic genome. In addition to
      aldehyde metabolizing capacity, ALDHs have additional catalytic (e.g. esterase
      and reductase) and non-catalytic activities. The latter include functioning as
      structural elements in the eye (crystallins) and as binding molecules to
      endobiotics and xenobiotics. Mutations in human ALDH genes and subsequent inborn
      errors in aldehyde metabolism are the molecular basis of several diseases. Most
      recently ALDH polymorphisms have been associated with gout and osteoporosis.
      Aldehyde dehydrogenase enzymes also play important roles in embryogenesis and
      development, neurotransmission, oxidative stress and cancer. This article serves
      as a comprehensive review of the current state of knowledge regarding the ALDH
      superfamily and the contribution of ALDHs to various physiological and
      pathophysiological processes.

PMID- 23159888
TI  - Analysis of mammalian alcohol dehydrogenase 5 (ADH5): characterisation of rat
      ADH5 with comparisons to the corresponding human variant.
AB  - Alcohol dehydrogenase 5 (ADH5) is a member of the mammalian alcohol dehydrogenase
      family of yet undefined functions. ADH5 was first identified at the DNA level in
      human and deer mouse. A rat alcohol dehydrogenase structure of similar type has
      been isolated at the cDNA level using human ADH5 as a screening probe, where the
      rat cDNA structure displayed several atypical properties. mRNA for rat ADH5 was
      found in multiple tissues, especially in the kidney. In vitro translation
      experiments indicated that rat ADH5 is expressed as efficiently as ADH1 and
      furthermore, rat ADH5 was readily expressed in COS cells fused to Green
      Fluorescent Protein. However, no soluble ADH5 protein could be heterologously
      expressed in Escherichia coli cells with expression systems successfully used for
      other mammalian ADHs, including fused to glutathione-S-transferase. Molecular
      modelling of the enzyme indicated that the protein does not fold in a productive
      way, which can be the explanation why no stable and active ADH5 has been
      isolated. These results indicate that ADH5, while readily expressed at the mRNA
      level, does not behave similarly to other mammalian ADHs investigated. The
      results, in vitro and in silico, suggest an unstable ADH5 structure, which can
      explain for why no active and stable protein can be isolated. Further
      possibilities are conceivable: the ADH5 protein may have to interact with a
      stabiliser, or the gene is actually a pseudogene.

PMID- 23159889
TI  - Clinical manifestations and anti-phospholipid antibodies in 712 patients with
      systemic lupus erythematosus: evaluation of two diagnostic assays.
AB  - OBJECTIVES: To evaluate the agreement and performance of two tests for aPLs with
      regard to association with manifestations of the APS in patients with SLE.
      METHODS: We investigated 712 SLE patients and 280 population controls.
      Cardiolipin and beta(2) glycoprotein-I antibodies were measured with routine
      ELISA and a new automated method. Three positivity cut-offs (99%, 90% of controls
      and recommended cut-off by manufacturers) were used. Associations with previous
      thrombotic events, thrombocytopenia and, in a subgroup of patients, obstetric
      morbidity (n = 296) were evaluated. Results were compared with the LA test,
      performed in 380 patients. RESULTS: Inter-test agreement was moderate
      (demonstrated by kappa-values 0.16-0.71). Performance of the two tests was
      similar: at the 99th percentile cut-off, sensitivity for any thrombotic event
      ranged from 3.7% to 24.8%, while specificity was 84.7-97.7%. Regardless of assay,
      IgG isotypes were associated with venous thrombosis and ischaemic cerebrovascular
      disease, whereas aPLs of IgM isotype were weakly associated with ischaemic heart
      disease. Associations were greatly affected by aPL level. LA performed better
      than the specific aPL tests. LA was associated with any thrombotic event, odds
      ratio 5.4 (95% CI 3.1, 9.4), while the specific aPL tests ranged from non
      significant to an odds ratio of 1.9 (95% CI 1.03, 3.4) using criteria cut-off. LA
      was also convincingly associated with other APS manifestations. CONCLUSION: In
      relation to thrombotic manifestations, there was moderate agreement but no clear
      advantages when comparing a routine aPL ELISA with an automated method. APL
      isotype and titre as well as LA positivity are important for risk assessment in
      SLE patients.

PMID- 23159891
TI  - Systematic revision of the avian family Cisticolidae based on a multi-locus
      phylogeny of all genera.
AB  - The avian taxon Cisticolidae includes c. 110 species which are distributed
      throughout the tropical and subtropical parts of the Old World. We estimated the
      phylogeny of 47 species representing all genera assumed to be part of
      Cisticolidae based on sequence data from two mitochondrial and two nuclear
      markers, in total 3495bp. Bayesian inference and maximum likelihood analyses
      resulted in a generally well-supported phylogeny which clarified the position of
      several previously poorly known taxa. The placement of Drymocichla, Malcorus,
      Micromacronus, Oreophilais, Phragmacia, Phyllolais, Poliolais and Urorhipis in
      Cisticolidae is corroborated, whereas Rhopophilus and Scotocerca are removed from
      Cisticolidae. Urorhipis and Heliolais are placed in the genus Prinia whereas
      Prinia burnesii is shown to be part of Timaliidae, and is placed in the genus
      Laticilla. Although not recovered by all single loci independently, four major
      clades were identified within Cisticolidae, and one of these is here described as
      a new taxon (Neomixinae).

PMID- 23159890
TI  - Normalization of NF-kappaB activity in dorsal root ganglia neurons cultured from
      diabetic rats reverses neuropathy-linked markers of cellular pathology.
AB  - AIMS/HYPOTHESIS: Dorsal root ganglia (DRG) sensory neurons cultured from 3 to 5
      month streptozotocin (STZ)-induced diabetic rats exhibit structural and
      biochemical changes seen in peripheral nerve fibers in vivo, including axonal
      swellings, oxidative damage, reduced axonal sprouting, and decreased NF-kappaB
      activity. NF-kappaB is a transcription factor required by DRG neurons for
      survival and plasticity, and regulates transcription of antioxidant proteins
      (e.g. MnSOD). We hypothesized that the diabetes-induced decrease in NF-kappaB
      activity in DRG contributes to pathological phenomena observed in cultured DRG
      neurons from diabetic rats. METHODS: NF-kappaB localization was assessed in
      intact DRG and neuron cultures using immunostaining. NF-kappaB activity was
      manipulated in sensory neuron cultures derived from age-matched normal or 3-5
      month STZ-diabetic rats using pharmacological means and lentiviral expression of
      shRNA. The impact of diabetes and altered NF-kappaB activity on neuronal
      phenotype involved analysis of neurite outgrowth, neurite morphology, oxidative
      stress (lipid peroxidation) and expression of MnSOD. RESULTS: STZ-induced
      diabetes caused a significant decrease in nuclear localization of NF-kappaB
      subunits p50 and c-rel, but no change in p65 in intact DRG. Inhibition of NF
      kappaB in normal neuron cultures significantly increased axonal swellings and
      oxidative stress, and reduced both neurite outgrowth and expression of MnSOD.
      These phenomena mimicked markers of pathology in cultured DRG neurons from
      diabetic rats. Enhancement of NF-kappaB activity in cultured diabetic DRG neurons
      ameliorated the sub-optimal neurite outgrowth and MnSOD levels triggered by
      diabetes. Exogenous insulin enhanced nuclear localization of p50 and c-rel but
      not p65 in diabetic neuronal cultures. CONCLUSION/INTERPRETATION: The diabetes
      induced decrease of nuclear localization of NF-kappaB subunits p50 and c-rel in
      DRG contributes to development of in vitro markers of peripheral neuropathy,
      possibly through impaired mitochondrial ROS scavenging by deficient MnSOD.

PMID- 23159892
TI  - A multilocus perspective on phylogenetic relationships in the Namib darkling
      beetle genus Onymacris (Tenebrionidae).
AB  - Tenebrionid beetles, common constituent faunae of arid ecosystems worldwide, are
      particularly abundant in Africa's Namib and Kalahari deserts. Within this region,
      flightless, diurnal members of the tribe Adesmiini are among the more intensively
      studied of all desert beetles, especially with regard to ecology. Much of this
      research centers on Onymacris, a psammophilous genus largely endemic to the
      Namib. Here we present the first molecular phylogenetic analysis conducted for
      Onymacris, emphasizing relationships among other adesmiines. Our multilocus
      phylogeny identifies a strongly supported clade containing Onymacris and two
      other genera, Eustolopus and Physadesmia-an assemblage recovered in earlier
      morphological analyses. However, Onymacris is not monophyletic; rather, we
      demonstrate its paraphyly with respect to the genus Physadesmia, identified as
      the sister taxon to the white-bodied species of Onymacris. In turn, the
      Physadesmia-'white'Onymacris clade is the sister group to the remaining (black
      bodied) Onymacris. Non-monophyly of 'black' versus 'white'Onymacris is
      corroborated by distribution patterns and nodal age estimates, which suggest
      separate origins in different dune systems.

PMID- 23159893
TI  - Molecular phylogeny of black fungus gnats (Diptera: Sciaroidea: Sciaridae) and
      the evolution of larval habitats.
AB  - The phylogeny of the family Sciaridae is reconstructed, based on maximum
      likelihood, maximum parsimony, and Bayesian analyses of 4809bp from two
      mitochondrial (COI and 16S) and two nuclear (18S and 28S) genes for 100 taxa
      including the outgroup taxa. According to the present phylogenetic analyses,
      Sciaridae comprise three subfamilies and two genus groups: Sciarinae,
      Chaetosciara group, Cratyninae, and Pseudolycoriella group+Megalosphyinae. Our
      molecular results are largely congruent with one of the former hypotheses based
      on morphological data with respect to the monophyly of genera and subfamilies
      (Sciarinae, Megalosphyinae, and part of postulated "new subfamily"); however, the
      subfamily Cratyninae is shown to be polyphyletic, and the genera Bradysia,
      Corynoptera, Leptosciarella, Lycoriella, and Phytosciara are also recognized as
      non-monophyletic groups. While the ancestral larval habitat state of the family
      Sciaridae, based on Bayesian inference, is dead plant material (plant
      litter+rotten wood), the common ancestors of Phytosciara and Bradysia are
      inferred to living plants habitat. Therefore, shifts in larval habitats from dead
      plant material to living plants may have occurred within the Sciaridae at least
      once. Based on the results, we discuss phylogenetic relationships within the
      family, and present an evolutionary scenario of development of larval habitats.

PMID- 23159894
TI  - Combining multiple autosomal introns for studying shallow phylogeny and taxonomy
      of Laurasiatherian mammals: Application to the tribe Bovini (Cetartiodactyla,
      Bovidae).
AB  - Mitochondrial sequences are widely used for species identification and for
      studying phylogenetic relationships among closely related species or populations
      of the same species. However, many studies of mammals have shown that the
      maternal history of the mitochondrial genome can be discordant with the true
      evolutionary history of the taxa. In such cases, the analyses of multiple nuclear
      genes can be more powerful for deciphering interspecific relationships. Here, we
      designed primers for amplifying 13 new exon-primed intron-crossing (EPIC)
      autosomal loci for studying shallow phylogeny and taxonomy of Laurasiatherian
      mammals. Three criteria were used for the selection of the markers: gene
      orthology, a PCR product length between 600 and 1200 nucleotides, and different
      chromosomal locations in the bovine genome. Positive PCRs were obtained from
      different species representing the orders Carnivora, Cetartiodactyla, Chiroptera,
      Perissodactyla and Pholidota. The newly developed markers were analyzed in a
      phylogenetic study of the tribe Bovini (the group containing domestic and wild
      cattle, bison, yak, African buffalo, Asian buffalo, and saola) based on 17 taxa
      and 18 nuclear genes, representing a total alignment of 13,095 nucleotides. The
      phylogenetic results were compared to those obtained from analyses of the
      complete mitochondrial genome and Y chromosomal genes. Our analyses support a
      basal divergence of the saola (Pseudoryx) and a sister-group relationship between
      yak and bison. These results contrast with recent molecular studies but are in
      better agreement with morphology. The comparison of pairwise nucleotide distances
      shows that our nuDNA dataset provides a good signal for identifying taxonomic
      levels, such as species, genera, subtribes, tribes and subfamilies, whereas the
      mtDNA genome fails because of mtDNA introgression and higher levels of homoplasy.
      Accordingly, we conclude that the genus Bison should be regarded as a synonym of
      Bos, with the European bison relegated to a subspecies rank within Bos bison. We
      compared our molecular dating estimates to the fossil record in order to propose
      a biogeographic scenario for the evolution of Bovini during the Neogene.

PMID- 23159895
TI  - Evolutionary history of nematodes associated with sweat bees.
AB  - Organisms that live in close association with other organisms make up a large
      part of the world's diversity. One driver of this diversity is the evolution of
      host-species specificity, which can occur via reproductive isolation following a
      host-switch or, given the correct circumstances, via cospeciation. In this study,
      we explored the diversity and evolutionary history of Acrostichus nematodes that
      are associated with halictid bees in North America. First, we conducted surveys
      of bees in Virginia, and found six halictid species that host Acrostichus. To
      test the hypothesis of cospeciation, we constructed phylogenetic hypotheses of
      Acrostichus based on three genes. We found Acrostichus puri and Acrostichus
      halicti to be species complexes comprising cryptic, host-specific species.
      Although several nodes in the host and symbiont phylogenies were congruent and
      tests for cospeciation were significant, the host's biogeography, the apparent
      patchiness of the association across the host's phylogeny, and the amount of
      evolution in the nematode sequence suggested a mixture of cospeciation, host
      switching, and extinction events instead of strict cospeciation. Cospeciation can
      explain the relationships between Ac. puri and its augochlorine hosts, but
      colonization of Halictus hosts is more likely than cospeciation. The nematodes
      are vertically transmitted, but sexual transmission is also likely. Both of these
      transmission modes may explain host-species specificity and congruent bee and
      nematode phylogenies. Additionally, all halictid hosts come from eusocial or
      socially polymorphic lineages, suggesting that sociality may be a factor in the
      suitability of hosts for Acrostichus.

PMID- 23159896
TI  - Outcomes for differentiated thyroid cancer in New Zealand: comparison of South
      Island and Auckland data.

PMID- 23159898
TI  - The demographics and prevalence of youth (15-24 year olds) with type 1 diabetes
      in the Canterbury District Health Board catchment area in 2010: has the
      prevalence changed since 2003?
AB  - AIM: The aim of the present study was to provide up-to-date descriptive
      information in relation to youth (15-24 years) with type 1 diabetes, residing
      within the Canterbury District Health Board (CDHB) catchment area. This included
      calculating the prevalence of type 1 diabetes in youth, and investigating whether
      there was an increase in the prevalence since a previous study reporting the
      prevalence of type 1 diabetes in youth in the CDHB in 2003. METHODS: Data were
      collected from multiple clinical and research sources. Descriptive information
      and demographic characteristics, including age, gender, ethnicity, deprivation
      level, and diabetes duration were gathered. The prevalence, stratified by age and
      ethnicity, was calculated using the 2006 population census data. RESULTS: There
      were 248 people with type 1 diabetes aged between 15 and 24 years residing within
      the CDHB area at the time of present study, giving a prevalence of 426 per
      100,000 European youth with type 1 diabetes. The prevalence is found to have
      increased by 45 per 100,000 (12%) since 2003, but was statistically
      insignificant. CONCLUSIONS: There was no statistically significant increase in
      the prevalence of type 1 diabetes in youth in the CDHB catchment area between
      2003 and 2010. However, the absolute figures of adolescents and young adults with
      type 1 diabetes have increased, which implies an increased demand on health care
      associated with diabetes compared to 7 years ago.

PMID- 23159897
TI  - Deaths due to differentiated thyroid cancer: a South Island, New Zealand
      experience: 1984-2009.
AB  - AIM: To assess differentiated thyroid cancer (DTC) deaths from the northern half
      of New Zealand's South Island. METHODS: Retrospective review of Christchurch
      Hospital Thyroid Clinic and Oncology Department clinical records of resident
      patients who died of differentiated thyroid cancer of follicular cell origin over
      the 25-year period 1984-2009. RESULTS: During the 25-year study period 25
      patients died from differentiated thyroid cancer. All patients (17 female, 8
      male) were Caucasian, with median age 65 years (47-86 years) at presentation.
      Most (24/25) patients presented with advanced (15 Stage IV, 9 Stage III) disease.
      Three patients initially presented with cervical lymphadenopathy and four
      patients with distant metastases--three patients with bone metastases, and one
      with a pleural effusion. The pathological classification of the tumours included
      14 papillary cancers (four were follicular variants), six follicular cancers and
      five Hurthle cell cancers. The majority of primary tumours were large (>4 cm) and
      11 were locally invasive. However one patient had a small (1.3 cm) papillary
      cancer and presented with a pleural effusion. Surgical removal of the primary
      tumour was attempted in 24 of the 25 patients, 18 received postoperative
      radioiodine 131I therapy, and three had external beam radiation therapy. The
      median survival from diagnosis was 5.5 years (0.2-22 years) with two Stage IV
      patients (both with Hurthle cell cancers) dying within 4 months. The majority of
      patients died of metastatic disease but seven died of local disease. CONCLUSIONS:
      During the 25-year study period, 25 patients died of differentiated thyroid
      cancer which approximates to one DTC death per year in our region. The median age
      at diagnosis was 65 years with no patients <45 years of age, and the female to
      male ration was 2.1:1. Most patients presented with advanced disease--7 patients
      (28%) had distant metastases. Hurthle cell cancers were over-represented (20%) in
      our series.

PMID- 23159899
TI  - Biosocial profile of New Zealand prosthetic eye wearers.
AB  - AIM: To describe the biosocial profile of New Zealand (NZ) artificial eye wearers
      and establish a basis for future research and international comparison. METHODS:
      This retrospective study surveyed 431 NZ artificial eye wearers to investigate
      their ethnicity, gender, age, causes of eye loss, age of current prosthesis,
      ocular prosthetic maintenance regimes and the extent and severity of discharge
      associated with prosthesis wear. RESULTS: Approximately 3000 people wear
      artificial eyes in NZ. Accidents were the main cause of eye loss prior to 1990
      and medical conditions have been the main cause since. In the 1960s, the ratio of
      men to women losing an eye from accidents was 5:1, but during the past decade the
      ratio was 1.4:1. Socket discharge occurred at least twice daily for one-third of
      the study group. CONCLUSIONS: Approximately 1 in 1440 people wear artificial eyes
      in NZ. Decline of eye loss due to accidents is consistent with decreasing
      workplace and traffic accidents and may be due to improved medical management,
      workplace safety standards and safer roads. Mucoid discharge is prevalent in the
      anophthalmic population of NZ and an evidence based treatment protocol for
      discharge associated with prosthesis wear is needed. Research into this
      distressing condition is planned.

PMID- 23159900
TI  - Gout in women: differences in risk factors in young and older women.
AB  - AIM: To describe the clinical characteristics of female patients with gout,
      assess risk factors in this group and to identify any differences between pre-
      and postmenopausal women with this diagnosis. METHODS: We retrospectively
      reviewed the case records of all women who were seen with gout in a secondary
      care setting (inpatient and outpatient) at Counties Manukau District Health Board
      between July 2007 and July 2008. Demographic data, risk factors for gout and
      information on urate-lowering therapy was collected. A cut-off of less than and
      equal to 50 years was used to estimate pre-menopausal status. RESULTS: 122/509
      (24%) of patients seen with gout were female. Fourteen female patients were less
      than or equal to 50 years of age; all of these patients were either Maori (43%)
      or of Pacific Island ethnicity (57%). Comorbidities in those =50 years old were
      renal impairment (78.6%), hypertension (64.3%), congestive heart failure (43%)
      and diabetes mellitus (42.9%). Comorbidities in women >50 years old were similar:
      hypertension (77%), renal impairment (70%), dyslipidemia (53%) and diabetes
      mellitus (50%). Ischemic heart disease was more common in older women (43% vs
      7%), P<0.01. Mean body mass index (BMI) was significantly higher in the younger
      women (43.5 vs 33.1), P<0.01. Half of all the female patients were on diuretics,
      and medication used to lower uric acid level was prescribed in 35.7% of women
      less than and equal to 50 years of age, and 42.59% of women >50 years of age.
      CONCLUSION: Women who develop gout are more likely to be over the age of 50, have
      other comorbidities and be on diuretics. In comparison, younger women who develop
      gout have similar risk factors but tended to have a higher body mass index and
      are more likely to be of Maori or Pacific Island ethnicity.

PMID- 23159901
TI  - Bariatric surgery makes dramatic difference to health-related quality of life.
AB  - AIM: To explore the impact of bariatric surgery on health-related quality of life
      (HRQoL). METHODS: An audit of patients referred for bariatric procedures.
      Patients completed Short Form-36 questionnaires at their first pre-operative
      clinic and at their 6-month follow up appointment after surgery. SF-36 scores
      were compared with standard parametric tests. RESULTS: 40 patients completed
      baseline SF-36 questionnaires and underwent bariatric surgery, 28 were surveyed
      again 6 months post-procedure during the audit period between December 2008 and
      December 2010. Twenty-three patients underwent laparoscopic Roux-en-Y gastric
      bypass and five underwent laparoscopic sleeve gastrectomy. The patients were
      predominantly New Zealand European, female, with a body mass index greater than
      40 kg/m2. Significant improvements in health-related quality of life were
      observed. The physical and mental component summary scores were initially well
      below the population norms, but increased to the norm 6 months after surgery.
      CONCLUSION: The HRQoL of morbidly obese patients significantly improves after
      bariatric surgery. Services including the SF-36 in their measurement
      armamentarium can demonstrate the Service's impact on patient-perceived outcomes
      in addition to clinically-focused outcomes.

PMID- 23159902
TI  - Undetected rheumatic heart disease revealed using portable echocardiography in a
      population of school students in Tairawhiti, New Zealand.
AB  - AIM: The aim of this programme was to find undetected rheumatic heart disease
      (RHD) in students from selected schools in the Tairawhiti region (eastern part of
      the North Island) of New Zealand. METHOD: Portable echocardiography was used to
      scan students in 5 urban and rural schools in Tairawhiti where the population is
      predominantly Maori. The age range of students in the urban schools was 10-13
      years and in the rural schools 5-17 years. Those with abnormal echocardiograms
      were referred for a paediatric consultation, with hospital-based echocardiography
      if required for the clarification of diagnoses and further management. RESULTS: A
      total of 685 students, representing over 95% of the schools' students, consented
      to having echocardiographic scanning. After repeat hospital based
      echocardiography for 11 students, a total of 52 scans were regarded as abnormal.
      In this population definite (n=4) or probable (n=7) RHD was found in 11 students
      a prevalence of 1.61% (95%CIs 0.80-2.85). Possible RHD was found in 19 students.
      Previously undetected confirmed (n=1) or probable (n=7) RHD was found in 8
      students a prevalence of 1.17% (95%CIs 0.51-2.29). Congenital heart defects (CHD)
      were found in 22 students a prevalence of 3.21% (95%CIs 2.02-4.83). CONCLUSION:
      Echocardiography was a popular modality and detected a significant burden of
      previously unknown RHD in this young Maori population who are now receiving
      penicillin. However, echocardiography detected a greater prevalence of possible
      RHD for which optimum management is at present uncertain. Echocardiography also
      detected students with a range of severity of CHD. Screening with
      echocardiography for RHD would involve a significant use of public health,
      paediatric and cardiac resources with 7.6% of students and their families
      requiring clinical consultations and ongoing management of the abnormal
      echocardiographic results.

PMID- 23159903
TI  - A decade of serious non-fatal assault in New Zealand.
AB  - AIM: To describe the distribution of, and trends in, the characteristics of
      serious non-fatal assault injury for the period 2000-2009. METHODS: Serious non
      fatal hospitalised assault injury for the 2000-2009 period were identified and
      described by: sociodemographic characteristics, location of incidents, methods
      used to inflict injury, alcohol involvement, and nature of injury. Trends in
      assault by age, gender, and method were examined. RESULTS: Males, 15-24 year
      olds, Maori, Pacific Islanders, and those from deprived neighbourhoods had
      markedly elevated assault rates. Assault by bodily force and head injuries
      predominated with the former being the major category of assault that increased
      the most over time CONCLUSIONS: There is a disturbing level of serious assault in
      New Zealand and the situation is getting worse. We need to review current efforts
      to prevent these incidents.

PMID- 23159904
TI  - Non-traumatic spontaneous spinal subdural haematoma.
AB  - We are presenting a case of non-traumatic spontaneous spinal subdural hematoma in
      a patient on warfarin and fluoxetine. This diagnosis should be considered early
      in patients who are on warfarin or fluoxetine or both presenting with acute
      neurological abnormalities of the limbs, and early decompression could result in
      good neurological outcome.

PMID- 23159905
TI  - Right atrial mass--a venous thrombosis in transit.
AB  - Right heart thrombi are unusual complications of pulmonary embolism that are
      associated with a high early mortality. We present a case and transoesophageal
      echocardiography of a 65-year-old man who presented with pulmonary embolism,
      following routine knee replacement and was found to have a type A right heart
      thrombus. Despite the increased risk associated with this presentation, treatment
      with heparin alone was successful.

PMID- 23159906
TI  - Medical image. The malign face of atrial fibrillation.

PMID- 23159907
TI  - Medical image. Persistent fever in ulcerative colitis.

PMID- 23159908
TI  - Premature failure of artificial joint components.

PMID- 23159909
TI  - Why just eat in, when you can also eat out?
AB  - The current working definition of autophagy is the following: all processes in
      which intracellular material is degraded within the lysosome/vacuole and where
      the macromolecular constituents are recycled. There are several ways to classify
      the different types of autophagy. For example, we can separate autophagy into two
      primary types, based on the initial site of cargo sequestration. In particular,
      during microautophagy and chaperone-mediated autophagy, uptake occurs directly at
      the limiting membrane of the lysosome or vacuole. In contrast, macroautophagy
      whether selective or nonselective-and endosomal microautophagy involve
      sequestration within an autophagosome or an omegasome, or late
      endosomes/multivesicular bodies, respectively; the key point being that in these
      types of autophagy the initial sequestration event does not occur at the limiting
      membrane of the degradative organelle. In any case, the cargo is ultimately
      delivered into the lysosome or vacuole lumen for subsequent degradation. Thus, I
      think most autophagy researchers view the degradative organelle as the ultimate
      destination of the pathway. Indeed, this fits with the general concept that
      organelles allow reactions to be compartmentalized. With regard to the lysosome
      or vacuole, this also confers a level of safety by keeping the lytic contents
      away from the remainder of the cell. If we are willing to slightly modify our
      definition of autophagy, with a focus on "degradation of a cell's own components
      through the lysosomal/vacuolar machinery," we can include a newly documented
      process, programmed nuclear destruction (PND).

PMID- 23159911
TI  - Synchronous right hepatectomy and cesarean section in a pregnant lady with
      hepatocellular carcinoma.
AB  - INTRODUCTION: Cancer in pregnancy is rare and hepatocellular carcinoma (HCC)
      during pregnancy is even rarer. Due to limited experience, management of these
      patients remains challenging. PRESENTATION OF CASE: A 33-year old pregnant lady
      presented with HCC at 28 weeks of gestation. She underwent synchronous cesarean
      section and right hepatectomy at 32 weeks of gestation. The post-operative course
      was uneventful. She was discharged home on day 10 after surgery. Histolopathology
      confirmed HCC. The surgical resection margins were clear. At a follow-up of 3
      months after surgery, the mother was disease free and the infant was well.
      DISCUSSION: HCC during pregnancy is extremely rare. The experience in its
      management and outcomes are lacking. In managing any patient diagnosed with a
      malignant neoplasm in pregnancy, both the mother and the fetus have to be
      considered. CONCLUSION: With adequate preoperative assessment and a good
      management strategy, good results can be obtained for both the mother and the
      baby for a pregnant patient with HCC.

PMID- 23159910
TI  - Tumor suppressive microRNA-218 inhibits cancer cell migration and invasion
      through targeting laminin-332 in head and neck squamous cell carcinoma.
AB  - Recent our microRNA (miRNA) expression signature revealed that expression of
      microRNA-218 (miR-218) was reduced in cancer tissues, suggesting a candidate of
      tumor suppressor in head and neck squamous cell carcinoma (HNSCC). The aim of
      this study was to investigate the functional significance of miR-218 and its
      mediated moleculer pathways in HNSCC. Restoration of miR-218 in cancer cells led
      to significant inhibition of cell migration and invasion activities in HNSCC cell
      lines (FaDu and SAS). Genome-wide gene expression analysis of miR-218
      transfectants and in silico database analysis showed that focal adhesion pathway
      was a promising candidate of miR-218 target pathways. The laminins are an
      important and biologically active part of the basal lamina, the function of that
      are various such as influencing cell differentiation, migration and adhesion as
      well as proliferation and cell survival. Interestingly, all components of laminin
      332 (LAMA3, LAMB3 and LAMC2) are listed on the candidate genes in focal adhesion
      pathway. Furthermore, we focused on LAMB3 which has a miR-218 target site and
      gene expression studies and luciferase reporter assays showed that LAMB3 was
      directly regulated by miR-218. Silencing study of LAMB3 demonstrated significant
      inhibition of cell migration and invasion. In clinical specimens with HNSCC, the
      expression levels of laminin-332 were significantly upregulated in cancer tissues
      compared to adjacent non-cancerous tissues. Our analysis data showed that tumor
      suppressive miR-218 contributes to cancer cell migration and invasion through
      regulating focal adhesion pathway, especially laminin-332. Tumor suppressive
      miRNA-mediated novel cancer pathways provide new insights into the potential
      mechanisms of HNSCC oncogenesis.

PMID- 23159912
TI  - Internal hernia through a peritoneal defect in the pouch of Douglas: Report of a
      case.
AB  - INTRODUCTION: Internal hernia is a rare entity which can cause intestinal
      obstruction. The most common type of internal hernia is the paraduodenal hernia
      which accounts for 53% of cases, and the internal hernia within the pelvis
      account for 7%. Perineal hernia, which is classified as pelvic hernia, usually
      occurs due to weakening of the pelvic floor musculature and thus, should be
      distinguished from the internal hernia caused by peritoneal defects in the pelvic
      cavity. PRESENTATION OF CASE: We present a case of 28-year-old female who
      presented intestinal obstruction. Conservative therapies failed and she required
      emergency laparotomy. The operative findings revealed a peritoneal defect of 2cm
      in diameter in the pouch of Douglas, through which the ileum was incarcerated and
      strangulated. The incarcerated bowel was reduced, and the intestinal color
      quickly returned to normal. Therefore a primary closure of the peritoneal defect
      was performed and the postoperative course was uneventful. DISCUSSION: A PubMed
      search for the case of internal hernia through a defect in the pouch of Douglas
      revealed only three, making this an extremely rare condition. CONCLUSION: Because
      of rarity of this hernia, the etiology is unknown. However, our patient is a
      young female with no history of pregnancy, abdominal surgery, or trauma,
      therefore the cause of the peritoneal defect is considered congenital.

PMID- 23159913
TI  - A note on the relevance of [6]-Gingerol for the prevention and/or treatment of
      Alzheimer's disease.

PMID- 23159914
TI  - The determination of exogenous formaldehyde in blood of rats during and after
      inhalation exposure.
AB  - Formaldehyde (FA) is suspected of being associated with the development of
      leukemia. An inhalation experiment with FA was performed in rats to study whether
      FA can enter the blood and could thus cause systemic toxicity in remote tissues
      such as the bone marrow. Therefore, a sophisticated analytical method was
      developed to detect blood concentrations of FA during and after single 6-h
      exposure by inhalation. In order to differentiate between exogenous and
      endogenous FA the rats were exposed to stable isotope ((13)C) labeled FA by
      inhalation. During and after exposure of the rats to (13)C-FA their blood was
      analyzed to determine the ratio between labeled and natural FA in blood and the
      total blood concentration of FA. With respect to sensitivity, with the applied
      method exogenous (13)C-FA could have been detected in blood at a concentration
      approximately 1.5% of the endogenous FA blood concentration. Exogenous (13)C-FA
      was not detectable in the blood of rats either during or up to 30 min after the
      exposure. It was concluded that the inhalation of (13)C-FA at 10 ppm for 6h did
      not result in an increase of the total FA concentration in blood.

PMID- 23159915
TI  - Simultaneously sensitive detection of multiple miRNAs based on a strand
      displacement amplification.
AB  - We reported an efficient strategy based on a strand displacement amplification
      for serum miRNA detection. In such a system, a multiplexed, sensitive and quick
      detection of miRNAs could be achieved through a combination of fluorescence
      labeled probes, a common primer and a polymerase. This could be potentially used
      in the clinical field to achieve early disease diagnosis and prognosis.

PMID- 23159916
TI  - Rheumatic manifestations of endocrine disease.
AB  - PURPOSE OF REVIEW: Musculoskeletal complaints are a feature of several endocrine
      diseases. This review will update clinicians on their association, presentation,
      and treatment. RECENT FINDINGS: To update clinicians on the recent literature as
      it is related to pathophysiology, genetic, and clinical findings on the
      association of these diseases and musculoskeletal complaints. SUMMARY:
      Rheumatologists in the clinic are faced with different presentations of various
      musculoskeletal complaints every day. Every new patient encounter requires the
      differential diagnosis of these complaints. The first task is usually to decide
      with what disease in internal medicine these complaints are associated. The
      endocrinopathies are a group of illnesses that either present initially or
      exhibit sometime during the course of the disease as a variety of musculoskeletal
      complaints. Rheumatic manifestations may often be the initial presentation of an
      endocrine disorder. Each endocrine disorder may also have its own arthritic
      complaints, which can present as a definitive rheumatic disease such as calcium
      pyrophosphate dihydrate deposition disease or as a rheumatic symptom such as
      diffuse arthralgia. The rheumatologist as well as the primary care physician
      should be knowledgeable about the ways in which muscles, tendons, ligaments, and
      joints are affected by diseases of the endocrine system.

PMID- 23159917
TI  - Transcription factors that control inner ear development and their potential for
      transdifferentiation and reprogramming.
AB  - Transcription factors (TFs) participate during various processes throughout inner
      ear development such as induction, morphogenesis and determination of cell fate
      and differentiation. The analysis of mouse mutants has been essential to define
      the requirement of different members of TF families during these processes. Next
      to their roles during normal development TFs have also been tested for their
      capacity to induce differentiation or reprogram cells upon misexpression.
      Recently the capacity of TFs to transdifferentiate easily accessible cells such
      as fibroblasts to highly specialized cell types has opened a new pathway for
      regenerative therapies. In this review the influence of TFs acting during
      different phases and processes of inner ear development will be summarized. A
      special focus will be given to TFs with a potential to reprogram or
      transdifferentiate cells to sensory cell types of the inner ear such as hair
      cells or neurons and thus may form part of future protocols directed to generate
      replacement cells in a clinical context.

PMID- 23159918
TI  - Comparison of forward (ear-canal) and reverse (round-window) sound stimulation of
      the cochlea.
AB  - The cochlea is normally driven with "forward" stimulation, in which sound is
      introduced to the ear canal. Alternatively, the cochlea can be stimulated at the
      round window (RW) using an actuator. During RW "reverse" stimulation, the
      acoustic flow starting at the RW does not necessarily take the same path as
      during forward stimulation. To understand the differences between forward and
      reverse stimulation, we measured ear-canal pressure, stapes velocity, RW
      velocity, and intracochlear pressures in scala vestibuli (SV) and scala tympani
      (ST) of fresh human temporal bones. During forward stimulation, the cochlear
      drive (differential pressure across the partition) results from the large
      difference in magnitude between the pressures of SV and ST, which occurs due to
      the high compliance of the RW. During reverse stimulation, the relatively high
      impedance of the middle ear causes the pressures of SV and ST to have similar
      magnitudes, and the differential pressure results primarily from the difference
      in phase of the pressures. Furthermore, the sound path differs between forward
      and reverse stimulation, such that motion through a third window is more
      significant during reverse stimulation. Additionally, we determined that although
      stapes velocity is a good estimate of cochlear drive during forward stimulation,
      it is not a good measure during reverse stimulation. This article is part of a
      special issue entitled "MEMRO 2012".

PMID- 23159919
TI  - Self-organization and entropy reduction in a living cell.
AB  - In this paper we discuss the entropy and information aspects of a living cell.
      Particular attention is paid to the information gain on assembling and
      maintaining a living state. Numerical estimates of the information and entropy
      reduction are given and discussed in the context of the cell's metabolic
      activity. We discuss a solution to an apparent paradox that there is less
      information content in DNA than in the proteins that are assembled based on the
      genetic code encrypted in DNA. When energy input required for protein synthesis
      is accounted for, the paradox is clearly resolved. Finally, differences between
      biological information and instruction are discussed.

PMID- 23159920
TI  - Generalized method for computation of true thickness and x-ray intensity
      information in highly blurred sub-millimeter bone features in clinical CT images.
AB  - In clinical computed tomography (CT) images, cortical bone features with sub
      millimeter (sub-mm) thickness are substantially blurred, such that their
      thickness is overestimated and their intensity appears underestimated. Therefore,
      any inquiry of the geometry or the density of such bones based on these images is
      severely error prone. We present a model-based method for estimating the true
      thickness and intensity magnitude of cortical and trabecular bone layers at
      localized regions of complex shell bones down to 0.25 mm. The method also
      computes the width of the corresponding point spread function. This approach is
      applicable on any CT image data, and does not rely on any scanner-specific
      parameter inputs beyond what is inherently available in the images themselves.
      The method applied on CT intensity profiles of custom phantoms mimicking shell
      bones produced average cortical thickness errors of 0.07 +/- 0.04 mm versus an
      average error of 0.47 +/- 0.29 mm in the untreated cases (t(55) = 10.92, p ?
      0.001)). Similarly, the average error of intensity magnitude estimates of the
      method were 22 +/- 2.2 HU versus an error of 445 +/- 137 HU in the untreated
      cases (t(55) = 26.48, p ? 0.001)). The method was also used to correct the CT
      intensity profiles from a cadaveric specimen of the craniofacial skeleton (CFS)
      in 15 different regions. There was excellent agreement between the corrections
      and uCT intensity profiles of the same regions used as a 'gold standard' measure.
      These results set the groundwork towards restoring cortical bone geometry and
      intensity information in entire image data sets. This information is essential
      for the generation of finite element models of the CFS that can accurately
      describe the biomechanical behavior of its complex thin bone structures.

PMID- 23159921
TI  - Ivabradine: an intelligent drug for the treatment of ischemic heart disease.
AB  - Heart rate (HR) is a precisely regulated variable, which plays a critical role in
      health and disease. Elevated resting HR is a significant predictor of all-cause
      and cardiovascular mortality in the general population and patients with
      cardiovascular disease (CVD). beta-blocking drugs exert negative effects on
      regional myocardial blood flow and function when HR reduction is eliminated by
      atrial pacing; calcium channel antagonists (CCAs) functionally antagonize
      coronary vasoconstriction mediated through alpha-adreno-receptors and are thus
      devoid of this undesired effect, but the compounds are nevertheless negative
      inotropes. From these observations derives the necessity to find alternative,
      more selective drugs to reduce HR through inhibition of specific electrical
      current (I(f)). Ivabradine (IVA) is a novel specific HR-lowering agent that acts
      in sinus atrial node (SAN) cells by selectively inhibiting the pacemaker I(f)
      current in a dose-dependent manner by slowing the diastolic depolarization slope
      of SAN cells, and by reducing HR at rest during exercise in humans. Coronary
      artery diseases (CAD) represent the most common cause of death in middle-aged and
      older adults in European Countries. Most ischemic episodes are triggered by an
      increase in HR, that induces an imbalance between myocardial oxygen delivery and
      consumption. IVA, a selective and specific inhibitor of the I(f) current which
      reduced HR without adverse hemodynamic effects, has clearly and unequivocally
      demonstrated its efficacy in the treatment of chronic stable angina pectoris
      (CSAP) and myocardial ischemia with optimal tolerability profile due to selective
      interaction with I(f) channels. The aim of this review is to point out the
      usefulness of IVA in the treatment of ischemic heart disease.

PMID- 23159922
TI  - Organophosphorus chemistry for the synthesis of dendrimers.
AB  - Dendrimers are multifunctional, hyperbranched and perfectly defined
      macromolecules, synthesized layer after layer in an iterative manner. Besides the
      nature of the terminal groups responsible for most of the properties, the nature
      of the internal structure, and more precisely of the branching points, is also of
      crucial importance. For more than 15 years, we have demonstrated that the
      presence of phosphorus atom(s) at each branching point of the dendrimeric
      structure is particularly important and highly valuable for three main reasons:
      (i) the versatility of phosphorus chemistry that allows diversified
      organochemistry for the synthesis of dendrimers; (ii) the use of 31P-NMR, which
      is a highly valuable tool for the characterization of dendrimers; (iii) some
      properties (in the fields of catalysis, materials, and especially biology), that
      are directly connected to the nature of the internal structure and of the
      branching points. This review will give an overview of the methods of synthesis
      of phosphorus-containing dendrimers, as well on the ways to graft phosphorus
      derivatives as terminal groups, with emphasis on the various roles played by the
      chemistry of phosphorus.

PMID- 23159923
TI  - Amelioration of dextran sodium sulfate-induced colitis in mice by Rhodobacter
      sphaeroides extract.
AB  - Bacteria can produce some compounds in response to their environment. These
      compounds are widely used in cosmetic and pharmaceutical applications. Some
      probiotics have immunomodulatory activities and modulate the symptoms of several
      diseases. Autoimmune diseases represent a complex group of conditions that are
      thought to be mediated through the development of autoreactive immunoresponses.
      Inflammatory bowel disease (IBD) is common autoimmune disease that affects many
      individuals worldwide. Previously, we found that the extracts of Rhodobacter
      sphaeroides (Lycogen) inhibited nitric oxide production and inducible nitric
      oxide synthase expression in activated macrophages. In this study, the effect of
      Lycogen, a potent anti-inflammatory agent, was evaluated in mice with dextran
      sodium sulfate (DSS)-induced colitis. Oral administration of Lycogen reduced the
      expressions of proinflammatory cytokines (tumor necrosis factor-alpha and
      interleukin-1beta) in female BABL/c mice. In addition, the increased number of
      bacterial flora in the colon induced by DSS was amelirated by Lycogen. The
      histological score of intestinal inflammation in 5% DSS-treated mice after oral
      administration of Lycogen was lower than that of control mice. Meanwhile, Lycogen
      dramatically prolonged the survival of mice with severe colitis. These findings
      identified that Lycogen is an anti-inflammatory agent with the capacity to
      ameliorate DSS-induced colitis.

PMID- 23159924
TI  - Monoterpenoid indole alkaloids from Alstonia yunnanensis and their cytotoxic and
      anti-inflammatory activities.
AB  - The 80% ethanol extract of Alstonia yunnanensis afforded five new monoterpenoid
      indole alkaloids: 11-hydroxy-6,7-epoxy-8-oxo-vincadifformine (1), 14-chloro-15
      hydroxy- vincadifformine (2), perakine N(4)-oxide (3), raucaffrinoline N(4)-oxide
      (4), and vinorine N(1),N(4)-dioxide (5), together with three known compounds: 11
      methoxy-6,7-epoxy-8-oxo- vincadifformine (6), vinorine N(4)-oxide (7) and
      vinorine (8). The structures of the isolated compounds were established based on
      1D and 2D (1H-1H-COSY, HMQC, HMBC, and ROESY) NMR spectroscopy, in addition to
      high resolution mass spectrometry. The isolated compounds were tested in vitro
      for cytotoxic potential against seven tumor cell lines and anti-inflammatory
      activities. Compounds 3, 4 and 7 exhibited weak cytotoxicity against the tested
      cell lines and selective inhibition of Cox-2 (> 85%).

PMID- 23159925
TI  - Caspase-8 and caspase-9 mediate thymocyte apoptosis in Trypanosoma cruzi acutely
      infected mice.
AB  - Trypanosoma cruzi acute infection leads to thymic atrophy, largely as a result of
      death of immature DP T cells. In a second vein, the glucocorticoid hormone
      imbalance promotes DP T cell apoptosis in infected mice. Herein, we assessed the
      involvement of caspase signaling in thymocyte death during T. cruzi acute
      infection. BALB/c mice were infected i.p. with 10(2) trypomastigote forms of T.
      cruzi and analyzed from 7 to 19 dpi. Thymocyte apoptosis was observed in early
      stages of infection, increasing along with time postinfection. Immature DN and DP
      as well as CD4(+) and CD8(+) thymocytes from infected mice showed increased
      activation of caspase-8, -9, and -3. In vitro treatment of thymocytes from
      infected mice with a general caspase inhibitor or the combination of caspase-8-
      and caspase-9-specific inhibitors increased the number of living thymocytes.
      Intrathymic injection of the general caspase inhibitor, but not caspase-8 or -9
      inhibitors individually, prevented thymic atrophy and thymocyte depletion in
      infected mice. Moreover, blockade of glucocorticoid receptor activity with RU486
      prevented DP thymocyte apoptosis, together with caspase-8 and -9 activation.
      These findings indicate that DP T cell apoptosis following experimental T. cruzi
      acute infection is dependent on glucocorticoid stimulation, promoting caspase-8
      and -9 activation.

PMID- 23159926
TI  - HMG-CoA reductase inhibitors activate caspase-1 in human monocytes depending on
      ATP release and P2X7 activation.
AB  - Recent studies have demonstrated the stimulatory effects of HMG-CoA reductase
      inhibitors, statins, on IL-1beta secretion in monocytes and suggest a crucial
      role for isoprenoids in the inhibition of caspase-1 activity. In this study, we
      further elucidated the molecular mechanisms underlying the stimulatory effects of
      statins on caspase-1. Three commonly recognized mechanistic models for NLRP3
      inflammasome activation (i.e., ATP/P2X7/K(+) efflux, ROS production, and
      lysosomal rupture) were investigated in statin-stimulated human THP-1 monocytes.
      We found that fluvastatin and lovastatin can synergize with LPS to trigger
      inflammasome activation. Moreover, statin-induced caspase-1 activation and IL
      1beta production in LPS-primed THP-1 cells are dependent on GGPP deficiency and
      P2X7 activation. In particular, increased ATP release accounts for the action of
      statins in P2X7 activation. We also provide evidence that statin-induced moderate
      ROS elevation is involved in this event. Moreover, the cathepsin B inhibitor was
      shown to reduce statin-induced IL-1beta secretion. Consistently statins can
      induce cathepsin B activation and lysosomal rupture, as evidenced by LysoTracker
      staining. Statins also increase intracellular ATP secretion and IL-1beta release
      in primary human monocytes and murine macrophages. Notably, exogenous ATP
      elicited P2X7 activation and consequent IL-1beta release, an index of direct
      NLRP3 inflammasome activation, were not altered by statins. Taken together,
      statin-induced enhancement of inflammasome activation in monocytes and
      macrophages covers multiple mechanisms, including increases in ATP release, ROS
      production, and lysosomal rupture. These data not only shed new insight into
      isoprenylation-dependent regulation of caspase-1 but also unmask mechanisms for
      statin-elicited inflammasome activation.

PMID- 23159927
TI  - CD4+ T lymphocytes in lung fibrosis: diverse subsets, diverse functions.
AB  - The discovery of several subsets of CD4(+) Th lymphocytes has contributed to
      refine and to challenge our understanding of the roles of CD4(+) T cells in the
      pathogenesis of fibrotic lung diseases. Here, we review recent findings,
      indicating that CD4(+) T subpopulations possess contrasting pro- and antifibrotic
      activities in human and experimental lung fibrosis. Special attention is given to
      delineate the activity of the newly discovered CD4(+) T lymphocyte subsets
      (Tregs, Th22, and Th9) on fibroblast function and matrix deposition through the
      release of growth factors, cytokines, and eicosanoids. It appears that the
      function of a CD4(+) T lymphocyte subset or of a cytokine can differ with the
      disease stage (acute vs. chronic), pulmonary localization (bronchial vs.
      alveolar), cellular level (epithelial cell vs. fibroblast), or immune environment
      (inflammatory or immunosuppressive). Integrating our recent understanding of the
      contrasting functions of T lymphocyte subsets in fibrosis provides new insights
      and opportunities for improved treatment strategies.

PMID- 23159928
TI  - Influence of the interdigitated gel phase in mixtures of ether-linked and
      monofluorinated ester-linked phospholipids.
AB  - To evaluate the influence of the hydrocarbon chain linkage on the thermodynamic
      phase behavior of spontaneously interdigitating lipids, mixtures of ether-linked
      1,2-di-O-hexadecyl-phosphocholine (DHPC) and ester-linked 1-palmitoyl-2-[16
      fluoropalmitoyl]sn-glycero-3-phosphocholine (F-DPPC) were studied. A combination
      of differential scanning calorimetry (DSC), fluorescence spectroscopy, and
      transmittance spectrophotometry was used. Small amounts of F-DPPC increase the
      pretransition temperature (T(p)) between the interdigitated gel phase (L(beta)I)
      and the ripple gel phase (P(beta)'). There are some signs of immiscibility where
      the non-interdigitated lipid is present in the phase diagram. However, at around
      20mol.% F-DPPC, the pretransition merges with the main transition and is no
      longer detectable as a separate entity. Additionally, the T(m) hysteresis
      increases steadily with higher mole fractions of F-DPPC. These results support
      that incorporating F-DPPC progressively stabilizes the L(beta)I phase of DHPC
      until the membrane is fully interdigitated below the main transition temperature
      (T(m)). The mixtures of F-DPPC and DHPC are miscible once the membrane is
      entirely interdigitated in the gel phase. Therefore, the ability of both lipids
      to interdigitate is an important factor controlling gel phase miscibility. Our
      results also demonstrate that the gel phase behavior of DHPC is highly sensitive
      to changes in its environment.

PMID- 23159929
TI  - Telomerase directly regulates NF-kappaB-dependent transcription.
AB  - Although elongation of telomeres is thought to be the prime function of
      reactivated telomerase in cancers, this activity alone does not account for all
      of the properties that telomerase reactivation attributes to human cancer cells.
      Here, we uncover a link between telomerase and NF-kappaB, a master regulator of
      inflammation. We observe that while blocking NF-kappaB signalling can inhibit
      effects of telomerase overexpression on processes relevant to transformation,
      increasing NF-kappaB activity can functionally substitute for reduced telomerase
      activity. Telomerase directly regulates NF-kappaB-dependent gene expression by
      binding to the NF-kappaB p65 subunit and recruitment to a subset of NF-kappaB
      promoters such as those of IL-6 and TNF-alpha, cytokines that are critical for
      inflammation and cancer progression. As NF-kappaB can transcriptionally
      upregulate telomerase levels, our findings suggest that a feed-forward regulation
      between them could be the key mechanistic basis for the coexistence of chronic
      inflammation and sustained telomerase activity in human cancers.

PMID- 23159930
TI  - Class IIa HDACs repressive activities on MEF2-depedent transcription are
      associated with poor prognosis of ER+ breast tumors.
AB  - MEF2s transcription factors and class IIa HDACs compose a fundamental axis for
      several differentiation pathways. Functional relationships between this axis and
      cancer are largely unexplored. We have found that class IIa HDACs are
      heterogeneously expressed and display redundant activities in breast cancer
      cells. Applying gene set enrichment analysis to compare the expression profile of
      a list of putative MEF2 target genes, we have discovered a correlation between
      the down-regulation of the MEF2 signature and the aggressiveness of ER(+) breast
      tumors. Kaplan-Meier analysis in ER(+) breast tumors evidenced an association
      between increased class IIa HDACs expression and reduced survival. The important
      role of the MEF2-HDAC axis in ER(+) breast cancer was confirmed in cultured
      cells. MCF7 ER(+) cells were susceptible to silencing of class IIa HDACs in terms
      of both MEF2-dependent transcription and apoptosis. Conversely, in ER(-) MDA-MB
      231 cells, the repressive influence of class IIa HDACs was dispensable.
      Similarly, a class IIa HDAC-specific inhibitor preferentially promoted the up
      regulation of several MEF2 target genes and apoptosis in ER(+) cell lines. The
      prosurvival function of class IIa HDACs could be explained by the repression of
      NR4A1/Nur77, a proapoptotic MEF2 target. In summary, our studies underscore a
      contribution of class IIa HDACs to aggressiveness of ER(+) tumors.-Clocchiatti,
      A., Di Giorgio, E., Ingrao, S., Meyer-Almes, F.-J., Tripodo, C., Brancolini, C.
      Class IIa HDACs repressive activities on MEF2-depedent transcription are
      associated with poor prognosis of ER(+) breast tumors.

PMID- 23159931
TI  - Targeted STIM deletion impairs calcium homeostasis, NFAT activation, and growth
      of smooth muscle.
AB  - The Ca(2+)-sensing stromal interaction molecule (STIM) proteins are crucial
      Ca(2+) signal coordinators. Cre-lox technology was used to generate smooth muscle
      (sm)-targeted STIM1-, STIM2-, and double STIM1/STIM2-knockout (KO) mouse models,
      which reveal the essential role of STIM proteins in Ca(2+) homeostasis and their
      crucial role in controlling function, growth, and development of smooth muscle
      cells (SMCs). Compared to Cre(+/-) littermates, sm-STIM1-KO mice showed high
      mortality (50% by 30 d) and reduced bodyweight. While sm-STIM2-KO was without
      detectable phenotype, the STIM1/STIM double-KO was perinatally lethal, revealing
      an essential role of STIM1 partially rescued by STIM2. Vascular and intestinal
      smooth muscle tissues from sm-STIM1-KO mice developed abnormally with distended,
      thinned morphology. While depolarization-induced aortic contraction was unchanged
      in sm-STIM1-KO mice, alpha1-adrenergic-mediated contraction was 26% reduced, and
      store-dependent contraction almost eliminated. Neointimal formation induced by
      carotid artery ligation was suppressed by 54%, and in vitro PDGF-induced
      proliferation was greatly reduced (79%) in sm-STIM1-KO. Notably, the Ca(2+) store
      refilling rate in STIM1-KO SMCs was substantially reduced, and sustained PDGF
      induced Ca(2+) entry was abolished. This defective Ca(2+) homeostasis prevents
      PDGF-induced NFAT activation in both contractile and proliferating SMCs. We
      conclude that STIM1-regulated Ca(2+) homeostasis is crucial for NFAT-mediated
      transcriptional control required for induction of SMC proliferation, development,
      and growth responses to injury.-Mancarella, S., Potireddy, S., Wang, Y., Gao, H.,
      Gandhirajan, K., Autieri, M., Scalia, R., Cheng, Z., Wang, H., Madesh, M.,
      Houser, S. R., Gill, D. L. Targeted STIM deletion impairs calcium homeostasis,
      NFAT activation, and growth of smooth muscle.

PMID- 23159932
TI  - Cooperation between beta- and gamma-cytoplasmic actins in the mechanical
      regulation of endothelial microparticle formation.
AB  - Elevated endothelial microparticle (MP) levels are observed in numerous diseases,
      increasingly supporting roles as effectors and valuable markers of vascular
      dysfunction. While a contractile role for the actin cytoskeleton has been
      implicated in vesiculation, i.e., MP production, the precise interactions and
      mechanisms of its constituents, beta- and gamma-cytoplasmic actins, is unknown.
      Human cerebral microvascular endothelial cells were stimulated with known
      agonists, and vesiculation development was monitored by scanning electron
      microscopy (SEM) and flow cytometry. These data in combination provide new
      insight into the kinetics, patterns of vesiculating cell recruitment, and degrees
      of response specific to stimuli. Reorganization of beta- and gamma-actins, F
      actin, vinculin, and talin accompanied significant MP release. beta-Actin
      redistribution into basal stress fibers following stimulation was associated with
      increased apically situated actin-rich particulate structures, which in turn
      directly correlated with electron-lucent membrane protrusions observed by SEM. Y
      27632 Rho-kinase inhibition abolished basal beta-actin fiber formation,
      minimizing apically associated actin-rich structures, significantly reducing
      membrane protrusions and MP release to near basal levels. Cytoskeletal protein
      expression and distribution varied between MPs and mother cells, as determined by
      Western blot. These data strongly suggest that beta-actin plays an active
      facilitative role in agonist-induced protuberance formation, through mechanical
      interactions with newly described actin-rich structures.

PMID- 23159933
TI  - Monocytes/macrophages prevent healing defects and left ventricular thrombus
      formation after myocardial infarction.
AB  - Myocardial infarction (MI) leads to rapid necrosis of cardiac myocytes. To
      achieve tissue integrity and function, inflammatory cells are activated,
      including monocytes/macrophages. However, the effect of monocyte/macrophage
      recruitment after MI remains poorly defined. After experimental MI, monocytes and
      macrophages were depleted through serial injections of clodronate-containing
      liposomes. Monocyte/macrophage infiltration was reduced in the myocardium after
      MI by active treatment. Mortality was increased due to thromboembolic events in
      monocyte- and macrophage-depleted animals (92 vs. 33%; P<0.01). Left ventricular
      thrombi were detectable as early as 24 h after MI; this was reproduced in a
      genetic model of monocyte/macrophage ablation. A general prothrombotic state,
      increased infarct expansion, and deficient neovascularization were not observed.
      Severely compromised extracellular matrix remodeling (collagen I, placebo
      liposome vs. clodronate liposome, 2.4 +/- 0.2 vs. 0.8 +/- 0.2 arbitrary units;
      P<0.001) and locally lost integrity of the endocardium after MI are potential
      mechanisms. Patients with a left ventricular thrombus had a relative decrease of
      CD14CD16 monocyte/macrophage subsets in the peripheral blood after MI (no
      thrombus vs. thrombus, 14.2 +/- 0.9 vs. 7.80 +/- 0.4%; P<0.05). In summary,
      monocytes/macrophages are of central importance for healing after MI. Impaired
      monocyte/macrophage function appears to be an unrecognized new pathophysiological
      mechanism for left ventricular thrombus development after MI.

PMID- 23159935
TI  - Avoiding the oligomeric state: alphaB-crystallin inhibits fragmentation and
      induces dissociation of apolipoprotein C-II amyloid fibrils.
AB  - The in vivo aggregation of proteins into amyloid fibrils suggests that cellular
      mechanisms that normally prevent or reverse this aggregation have failed. The
      small heat-shock molecular chaperone protein alphaB-crystallin (alphaB-c)
      inhibits amyloid formation and colocalizes with amyloid plaques; however, the
      physiological reason for this localization remains unexplored. Here, using
      apolipoprotein C-II (apoC-II) as a model fibril-forming system, we show that
      alphaB-c binds directly to mature amyloid fibrils (Kd 5.4 +/- 0.5 MUM). In doing
      so, alphaB-c stabilized the fibrils from dilution-induced fragmentation, halted
      elongation of partially formed fibrils, and promoted the dissociation of mature
      fibrils into soluble monomers. Moreover, in the absence of dilution, the
      association of alphaB-c with apoC-II fibrils induced a 14-fold increase in
      average aggregate size, resulting in large fibrillar tangles reminiscent of
      protein inclusions. We propose that the binding of alphaB-c to fibrils prevents
      fragmentation and mediates the lateral association of fibrils into large
      inclusions. We further postulate that transient interactions of apoC-II with
      alphaB-c induce a fibril-incompetent monomeric apoC-II form, preventing
      oligomerization and promoting fibril dissociation. This work reveals previously
      unrecognized mechanisms of alphaB-c chaperone action in amyloid assembly and
      fibril dynamics, and provides a rationale for the in vivo colocalization of small
      heat-shock proteins with amyloid deposits.-Binger, K. J., Ecroyd, H., Yang, S.,
      Carver, J. A., Howlett, G. J., Griffin, M. D. W. Avoiding the oligomeric state:
      alphaB-crystallin inhibits fragmentation and induces dissociation of
      apolipoprotein C-II amyloid fibrils.

PMID- 23159934
TI  - Nonspecific sarcolemmal cation channels are critical for the pathogenesis of
      malignant hyperthermia.
AB  - Malignant hyperthermia (MH) susceptibility has been attributed to a leaky
      sarcoplasmic reticulum (SR) caused by missense mutations in RYR1 or CACNA1S, and
      the MH crisis has been attributed solely to massive self-sustaining release of
      Ca(2+) from SR stores elicited by triggering agents. Here, we show in muscle
      cells from MH-RyR1(R163C) knock-in mice that increased passive SR Ca(2+) leak
      causes an enlarged basal influx of sarcolemmal Ca(2+) that results in chronically
      elevated myoplasmic free Ca(2+) concentration ([Ca(2+)]i) at rest. We discovered
      that Gd(+3) and GsMTx-4 were more effective than BTP2 or expression of the
      dominant-negative Orai1(E190Q) in reducing both Ca(2+) entry and [Ca(2+)]i,
      implicating a non-STIM1/Orai1 SOCE pathway in resetting resting [Ca(2+)]i.
      Indeed, two nonselective cationic channels, TRPC3 and TRPC6, are overexpressed,
      and [Na]i is chronically elevated in MH-RyR1(R163C) muscle cells. [Ca(2+)]i and
      [Na(+)]i are persistently elevated in vivo and further increased by halothane in
      MH-RyR1(R163C/WT) muscle. These increases are markedly attenuated by local
      perfusion of Gd(+3) or GsMTx-4 and completely suppressed by dantrolene. These
      results contribute a new paradigm for understanding MH pathophysiology by
      demonstrating that nonselective sarcolemmal cation channel activity plays a
      critical role in causing myoplasmic Ca(2+) and Na(+) overload both at rest and
      during the MH crisis.-Eltit, J. M., Ding, X., Pessah, I. N., Allen, P. D., Lopez,
      J. R. Nonspecific sarcolemmal cation channels are critical for the pathogenesis
      of malignant hyperthermia.

PMID- 23159936
TI  - Calmodulin activates neuronal nitric oxide synthase by enabling transitions
      between conformational states.
AB  - We recently showed that inducible nitric oxide synthase conformational
      intermediates can be resolved via FMN fluorescence lifetimes. Here we show that
      neuronal NOS activation by calmodulin removes constraints favoring a closed
      'input state', increasing occupation of other states and facilitating
      conformational transitions. The 90 ps FMN input state lifetime distinguishes it
      from ~4 ns 'open' states in which FMN does not interact strongly with other
      groups, or 0.9 ns output states in which FMN interacts with ferriheme. Enablement
      of the conformational cycle is an important paradigm for control in nNOS and
      related enzymes, and may extend to other control modalities.

PMID- 23159937
TI  - Transient receptor potential N (TRPN1) from Xenopus interacts with the penta-EF
      hand protein peflin.
AB  - TRPN1 is a candidate mechanotransduction channel in Drosophila and Caenorhabditis
      elegans, also present in hair cells of lower vertebrates. At its N-terminal
      cytoplasmic tail it contains 28 ankyrin repeats. We performed a yeast two-hybrid
      screen with the N-terminal ankyrin repeats of Xenopus TRPN1 as bait and
      identified the Penta-EF-hand protein peflin as a putative interaction partner. We
      confirmed this interaction by GST pulldown assays and by co-localization in an
      epithelial cell model. Collectively, our study identifies peflin as an
      interaction partner of TRPN1 in vitro.

PMID- 23159938
TI  - Characterization of the novel protein P9TLDR (temporal lobe down-regulated) with
      a brain-site-specific gene expression modality in Alzheimer's disease brain.
AB  - Alzheimer's disease (AD) is an aging-related neurodegenerative disorder
      characterized by irreversible loss of higher cognitive functions. The disease is
      characterized by the presence of amyloid plaques and neurofibrillary tangles
      (NFT). In the current study we isolated from an intra-cerebral brain-site
      specific (AD temporal lobe vs. AD occipital lobe) polymerase chain reaction (PCR)
      select cDNA suppression subtractive hybridization (PCR-cDNA-SSH) expression
      analysis the novel gene P9TLDR, potentially a microtubule-associated protein
      involved in neuronal migration, with an altered expression pattern: down
      regulated in the temporal lobe cortex of early stage AD brains. In an in vitro AD
      related cell model, amyloid-beta peptide (Abeta)-treated neurons, reduced P9TLDR
      expression correlated with increased tau protein phosphorylation. In conclusion,
      interference with the P9TLDR signalling pathways might be a therapeutic strategy
      for the treatment of AD.

PMID- 23159939
TI  - In situ UDP-glucose regeneration unravels diverse functions of plant secondary
      product glycosyltransferases.
AB  - The catalytic function of plant secondary product glycosyltransferases (PSPGs)
      was investigated by coupling the activities of recombinant flavonoid
      glucosyltransferases having different regiospecificities with sucrose synthase
      from Arabidopsis thaliana. In the present system, UDP, a product inhibitor of
      PSPGs, was removed from the reaction mixture and used for regeneration of UDP
      glucose by AtSUS1. The in situ UDP-glucose regeneration system not only enhanced
      the glucosylation efficiency but also unraveled the novel regioselectivity of
      PSPGs. The effect of the system was shown to be because of the removal of UDP
      from the reaction system and not because of the additional supply of UDP-glucose.

PMID- 23159940
TI  - Oligomeric structure of 14-3-3 protein: what do we know about monomers?
AB  - 14-3-3s predominantly form homo-/heterodimers that are in equilibrium with
      corresponding monomers. Dimer/monomer equilibrium depends on the nature and
      phosphorylation of Ser58 of certain 14-3-3 isoforms. The structure and properties
      of 14-3-3 dimers are well characterized, whereas 14-3-3 monomers are less
      investigated. Therefore design and analysis of dimer-incapable mutants of 14-3-3
      are important. Truncated or heavily mutated proteins are not ideal since their
      structure may be distorted. Phosphomimicking mutations, such as S58(D/E), induce
      incomplete dimer dissociation. A recently characterized monomeric 14-3-3 contains
      few mutations and retains the original secondary structure. Monomeric 14-3-3
      interacts with phosphorylated target proteins and has higher chaperone-like
      activity than dimeric 14-3-3. Further investigation of the properties of
      monomeric 14-3-3 is important for understanding its yet poorly characterized role
      in different cellular processes.

PMID- 23159941
TI  - Crystal structures of dye-decolorizing peroxidase with ascorbic acid and 2,6
      dimethoxyphenol.
AB  - The structure of dye-decolorizing peroxidase (DyP)-type peroxidase differs from
      that of other peroxidase families, indicating that DyP-type peroxidases have a
      different reaction mechanism. We have determined the crystal structures of DyP
      with ascorbic acid and 2,6-dimethoxyphenol at 1.5 and 1.4A, respectively. The
      common binding site for both substrates was located at the entrance of the second
      cavity leading from the DyP molecular surface to heme. This resulted in a
      hydrogen bond network connection between each substrate and the heme distal side.
      This network consisted of water molecules occupying the second cavity, heme 6
      propionate, Arg329, and Asn313. This network is consistent with the proton
      transfer pathway from substrate to DyP.

PMID- 23159942
TI  - Autistic-like behavioral phenotypes in a mouse model with copy number variation
      of the CAPS2/CADPS2 gene.
AB  - Ca2+-dependent activator protein for secretion 2 (CAPS2 or CADPS2) facilitates
      secretion and trafficking of dense-core vesicles. Recent genome-wide association
      studies of autism have identified several microdeletions due to copy number
      variation (CNV) in one of the chromosome 7q31.32 alleles on which the locus for
      CAPS2 is located in autistic patients. To evaluate the biological significance of
      reducing CAPS2 copy number, we analyzed CAPS2 heterozygous mice. Our present
      findings suggest that adequate levels of CAPS2 protein are critical for normal
      brain development and behavior, and that allelic changes due to CNV may
      contribute to autistic symptoms in combination with deficits in other autism
      associated genes.

PMID- 23159944
TI  - Eccrine sweat glands are major contributors to reepithelialization of human
      wounds.
AB  - Eccrine sweat glands are skin-associated epithelial structures (appendages) that
      are unique to some primates including humans and are absent in the skin of most
      laboratory animals including rodents, rabbits, and pigs. On the basis of the
      known importance of other skin appendages (hair follicles, apocrine glands, and
      sebaceous glands) for wound repair in model animals, the present study was
      designed to assess the role of eccrine glands in the repair of wounded human
      skin. Partial-thickness wounds were generated on healthy human forearms, and
      epidermal repair was studied in skin biopsy samples obtained at precise times
      during the first week after wounding. Wound reepithelialization was assessed
      using immunohistochemistry and computer-assisted 3-dimensional reconstruction of
      in vivo wounded skin samples. Our data demonstrate a key role for eccrine sweat
      glands in reconstituting the epidermis after wounding in humans. More
      specifically, (i) eccrine sweat glands generate keratinocyte outgrowths that
      ultimately form new epidermis; (ii) eccrine sweat glands are the most abundant
      appendages in human skin, outnumbering hair follicles by a factor close to 3; and
      (iii) the rate of expansion of keratinocyte outgrowths from eccrine sweat glands
      parallels the rate of reepithelialization. This novel appreciation of the unique
      importance of eccrine sweat glands for epidermal repair may be exploited to
      improve our approaches to understanding and treating human wounds.

PMID- 23159943
TI  - miR-150 down-regulation contributes to the constitutive type I collagen
      overexpression in scleroderma dermal fibroblasts via the induction of integrin
      beta3.
AB  - Overexpression of integrins in dermal fibroblasts is thought to play a key role
      in the pathogenesis of systemic sclerosis (SSc), but the mechanism is unknown. We
      evaluated the possibility that microRNAs (miRNAs) are involved in the regulation
      of integrin beta3 in these cells. The miRNA expression profile was determined by
      miRNA PCR array and real-time PCR. Protein expression of integrin beta3 was
      determined by immunoblotting. In vivo detection of miRNA in paraffin section was
      performed by in situ hybridization. miR-150 expression was decreased in SSc
      fibroblasts both in vivo and in vitro. The transfection of miR-150 inhibitor into
      normal fibroblasts induced expression of integrin beta3, phosphorylated Smad3,
      and type I collagen, whereas forced overexpression of the miRNA resulted in their
      down-regulation in SSc fibroblasts. Treatment of SSc fibroblasts with 5-AdC
      revealed that miR-150 down-regulation in these cells is caused by DNA
      methylation. In addition, we found that miR-150 is detectable and quantitative in
      serum. Serum miR-150 levels were decreased in SSc patients, and the SSc patients
      with lower serum miR-150 levels tended to have more severe clinical
      manifestations. miR-150 may play an important role in the pathogenesis of SSc via
      overexpression of integrin beta3. Investigation of the regulatory mechanisms of
      tissue fibrosis by miR-150 could lead to development of new diagnostic tools and
      new treatments using miRNA.

PMID- 23159945
TI  - Synergistic silencing by promoter methylation and reduced AP-2alpha
      transactivation of the proapoptotic HRK gene confers apoptosis resistance and
      enhanced tumor growth.
AB  - The Harakiri (HRK) gene encodes an important proapoptotic mitochondrial protein
      of the Bcl-2 family. HRK is expressed in normal tissues but is decreased in many
      cancers such as melanoma, the mechanisms of which have not been fully elucidated.
      Here, we demonstrate that HRK is silenced by hypermethylation of a major proximal
      CpG island in the HRK promoter. Furthermore, we show that HRK is a novel target
      gene regulated by the transcription factor AP-2alpha, which interacts with an AP
      2alpha binding site in the HRK promoter. Hypermethylation of the major proximal
      CpG island (which contains the AP-2alpha binding site within the most densely
      methylated -218- to -194-bp region) inhibited AP-2alpha binding and
      transcriptional activity. Artificial overexpression of AP-2alpha in melanoma
      cells up-regulated HRK transcription, which was further restored by treatment
      with DNA methyltransferase inhibitor 5-azacytidine. Artificial overexpression of
      HRK by recombinant adenovirus induced caspase-dependent apoptosis, inhibited
      melanoma cell growth in vitro, and markedly reduced in vivo melanoma growth in a
      nude mouse xenograft model. RNA interference by siHRK or siAP-2alpha reversed the
      above effects. We conclude that the synergistic effects of HRK promoter
      hypermethylation and loss of AP-2alpha transactivation lead to HRK gene silencing
      and confer resistance to apoptosis and enhanced tumor growth. These novel
      molecular lesions may provide the basis for new therapeutic approaches to
      treating AP-2alpha- and HRK-deficient cancers.

PMID- 23159946
TI  - Histone acetyl transferase (HAT) HBO1 and JADE1 in epithelial cell regeneration.
AB  - HBO1 acetylates lysine residues of histones and is involved in DNA replication
      and gene transcription. Two isoforms of JADE1, JADE1S and JADE1L, bind HBO1 and
      promote acetylation of histones in chromatin context. We characterized the role
      of JADE1-HBO1 complexes in vitro and in vivo during epithelial cell replication.
      Down-regulation of JADE1 by siRNA diminished the rate of DNA synthesis in
      cultured cells, decreased endogenous HBO1 protein expression, and prevented
      chromatin recruitment of replication factor Mcm7, demonstrating that JADE1 is
      required for cell proliferation. We used a murine model of acute kidney injury to
      examine expression of HBO1-JADE1S/L in injured and regenerating epithelial
      tissue. In control kidneys, JADE1S, JADE1L, and HBO1 were expressed in nuclei of
      proximal and distal tubular epithelial cells. Ischemia and reperfusion injury
      resulted in an initial decrease in JADE1S, JADE1L, and HBO1 protein levels, which
      returned to baseline during renal recovery. HBO1 and JADE1S recovered as cell
      proliferation reached its maximum, whereas JADE1L recovered after bulk
      proliferation had ceased. The temporal expression of JADE1S correlated with the
      acetylation of histone H4 on lysines 5 and 12, but not with acetylation of
      histone H3 on lysine 14, demonstrating that the JADE1S-HBO1 complex specifically
      marks H4 during epithelial cell proliferation. These data implicate JADE1-HBO1
      complex in acute kidney injury and suggest distinct roles for JADE1 isoforms
      during epithelial cell recovery.

PMID- 23159948
TI  - Protective and pathological properties of IL-22 in liver disease: implications
      for viral hepatitis.
AB  - Chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infection affect >500
      million people worldwide and are significant causes of liver cirrhosis and
      hepatocellular carcinoma. The pathogenesis of HBV and HCV infection can vary
      widely with respect to the outcome of initial infection to self-resolving acute
      or chronic disease, the extent of viremia and liver inflammation during chronic
      infection, and the eventual development of liver cirrhosis and hepatocellular
      carcinoma. The host immune response is an important factor in the variable
      consequences of these infections, because the innate and adaptive intrahepatic
      antiviral responses are an intricate balance of immune effector cells and
      cytokines that control virus replication but can also cause liver damage. IL-22
      is an important cytokine that plays a pleiotropic protective, but sometimes also
      pathological, role in several tissues/organs, including the liver. Therefore, IL
      22 is likely to be an important factor in the pathogenesis and clinical outcome
      of HBV and HCV infection. However, the precise beneficial, and possible
      detrimental, effects of this cytokine may vary among different disease states
      that are associated with distinct inflammatory microenvironments. This review
      summarizes our understanding of the protective and pathological activities of IL
      22, with an emphasis on the liver, and discusses the implications of these
      effects as they relate to viral hepatitis.

PMID- 23159947
TI  - The prolactin receptor transactivation domain is associated with steroid hormone
      receptor expression and malignant progression of breast cancer.
AB  - The polypeptide hormone prolactin (PRL) stimulates breast epithelial cell growth,
      differentiation, and motility through its cognate receptor, PRLr. PRLr is
      expressed in most breast cancers; however, its exact role remains elusive. Our
      laboratory previously described a novel mode of PRLr signaling in which Stat5a
      mediated transcription is regulated through ligand-induced phosphorylation of the
      PRLr transactivation domain (TAD). Herein, we used a PRLr transactivation
      deficient mutant (PRLrYDmut) to identify novel TAD-specific target genes.
      Microarray analysis identified 120 PRL-induced genes up-regulated by wild type
      but not PRLrYDmut. Compared with control, PRLr expression significantly induced
      expression of approximately 4700 PRL-induced genes, whereas PRLrYDmut ablated
      induction of all but 19 of these genes. Ingenuity pathway analysis found that the
      PRLr TAD most profoundly affected networks involving cancer and proliferation. In
      support of this, PRLrYDmut expression reduced anchorage-dependent and anchorage
      independent growth. In addition, pathway analysis identified a link between the
      PRLr TAD and the estrogen and progesterone receptors (ERalpha/PR). Although
      neither ERalpha nor PR was identified as a PRL target gene, a TAD mutation
      significantly impaired ERalpha/PR expression and estrogen responsiveness. TMA
      analysis revealed a marked increase in nuclear, but not cytoplasmic, PRLr TAD
      phosphorylation as a function of neoplastic progression. We propose that PRLr TAD
      phosphorylation contributes to breast cancer pathogenesis, in part through
      regulation of ERalpha and PR, and has potential utility as a biomarker in this
      disease.

PMID- 23159949
TI  - Gut bacteria drive Kupffer cell expansion via MAMP-mediated ICAM-1 induction on
      sinusoidal endothelium and influence preservation-reperfusion injury after
      orthotopic liver transplantation.
AB  - Bacteria in the gut microbiome shed microbial-associated molecule patterns
      (MAMPs) into the portal venous circulation, where they augment various aspects of
      systemic immunity via low-level stimulation. Because the liver is immediately
      downstream of the intestines, we proposed that gut-derived MAMPs shape liver
      immunity and affect Kupffer cell (KC) phenotype. Germ-free (GF), antibiotic
      treated (AVMN), and conventional (CL) mice were used to study KC development,
      function, and response to the significant stress of cold storage, reperfusion,
      and orthotopic transplantation. We found that a cocktail of physiologically
      active MAMPs translocate into the portal circulation, with flagellin (Toll-like
      receptor 5 ligand) being the most plentiful and capable of promoting hepatic
      monocyte influx in GF mice. In MAMP-deficient GF or AVMN livers, KCs are lower in
      numbers, have higher phagocytic activity, and have lower major histocompatibility
      complex II expression. MAMP-containing CL livers harbor significantly increased
      KC numbers via induction of intercellular adhesion molecule 1 on liver sinusoidal
      endothelium. These CL KCs have a primed yet expected phenotype, with increased
      major histocompatibility complex class II and lower phagocytic activity that
      increases susceptibility to liver preservation/reperfusion injury after
      orthotopic transplantation. The KC number, functional activity, and maturational
      status are directly related to the concentration of gut-derived MAMPs and can be
      significantly reduced by broad-spectrum antibiotics, thereby affecting
      susceptibility to injury.

PMID- 23159950
TI  - The role and regulation of human Th17 cells in tumor immunity.
AB  - T helper 17 (Th17) cells play critical roles in the pathogenesis of inflammatory
      and autoimmune diseases, as well as in host protection against pathogens. The
      contribution of Th17 cells to human tumor immunity, however, remains largely
      unknown. Since their identification in 2005, Th17 cells have been extensively
      studied in mouse tumor models and human cancer patients. Although accumulating
      data suggest the importance of Th17 cells to tumor immunity, conclusions
      regarding the functional role of Th17 cells remain controversial. In this review,
      we summarize current knowledge regarding the regulation and functional role of
      Th17 cells in human cancers. In particular, we emphasize several recently
      identified characteristics of Th17 cells, including plasticity, their
      relationship with regulatory T cells, and Th17 cell heterogeneity in the tumor
      microenvironment. Improved understanding of these issues is critical to
      elucidating the role of Th17 cells in antitumor immunity and for the design of
      novel therapeutic approaches specifically targeting Th17 cells.

PMID- 23159951
TI  - Glucagon-like peptide-1 receptor agonist inhibits asymmetric dimethylarginine
      generation in the kidney of streptozotocin-induced diabetic rats by blocking
      advanced glycation end product-induced protein arginine methyltranferase-1
      expression.
AB  - Advanced glycation end products (AGEs) and their receptor (RAGE) play a role in
      diabetic nephropathy. Asymmetric dimethylarginine (ADMA), an endogenous inhibitor
      of nitric oxide synthase, contributes to diabetic nephropathy. We have found that
      glucagon-like peptide-1 (GLP-1) inhibits the AGE-induced inflammatory reactions
      in endothelial cells. However, effects of GLP-1 on the AGE-RAGE-ADMA axis are
      unknown. This study examined the effects of GLP-1 on reactive oxygen species
      (ROS) generation, gene expression of protein arginine methyltransfetase-1 (PRMT
      1), an enzyme that mainly generates ADMA, and ADMA levels in human proximal
      tubular cells. Streptozotocin-induced diabetic rats received continuous i.p.
      infusion of 0.3 MUg of vehicle or 1.5 MUg of the GLP-1 analog exendin-4 per
      kilogram of body weight for 2 weeks. We further investigated whether and how
      exendin-4 treatment reduced ADMA levels and renal damage in streptozotocin
      induced diabetic rats. GLP-1 inhibited the AGE-induced RAGE and PRMT-1 gene
      expression, ROS, and ADMA generation in tubular cells, which were blocked by
      small-interfering RNAs raised against GLP-1 receptor. Exendin-4 treatment
      decreased gene expression of Rage, Prmt-1, Icam-1, and Mcp-1 and ADMA level;
      reduced urinary excretions of 8-hydroxy-2'-deoxyguanosine and albumin; and
      improved histopathologic changes of the kidney in diabetic rats. Our present
      study suggests that GLP-1 receptor agonist may inhibit the AGE-RAGE-mediated ADMA
      generation by suppressing PRMT-1 expression via inhibition of ROS generation,
      thereby protecting against the development and progression of diabetic
      nephropathy.

PMID- 23159953
TI  - The contribution of previous episodes of pain, pain intensity, physical
      impairment, and pain-related fear to disability in patients with chronic
      mechanical neck pain.
AB  - OBJECTIVE: The influence of physical and psychosocial variables on self-rated
      disability in patients with chronic mechanical neck pain has not been fully
      determined. This study examined the relationship of pain, physical impairment,
      and pain-related fear to disability in individuals with chronic mechanical neck
      pain. DESIGN: A cross-sectional study was conducted. Ninety-seven (n = 97)
      subjects (28 men, 69 women; mean age, 39.3 yrs) with chronic mechanical neck pain
      were prospectively recruited. Demographic information, duration of pain symptoms,
      pain intensity, pain-related fear, and cervical range of motion were collected on
      all subjects. Self-reported disability was measured with the Neck Disability
      Index. Correlation and regression analyses were performed to determine the
      association among the variables and to determine the proportions of explained
      variance in disability. RESULTS: Significant positive correlations existed
      between disability and previous history of neck pain (r = 0.45; P < 0.001),
      disability and pain intensity (r = 0.32, P = 0.01), and disability and
      kinesiophobia (r = 0.23, P = 0.02). In addition, a significant negative
      correlation existed between disability and cervical extension range of motion (r
      = -0.18, P = 0.04). Stepwise regression analyses revealed that previous neck pain
      episodes, intensity of neck pain, kinesiophobia, and cervical extension range of
      motion were significant predictors of disability (r = 0.400; r adjusted = 0.372;
      F = 14.64; P < 0.001). CONCLUSIONS: This study found that previous episodes of
      neck pain, pain intensity, pain-related fear, and cervical extension range of
      motion explained 37.2% of the variability of self-report disability. Future
      longitudinal studies will help to determine the clinical implications of these
      findings.

PMID- 23159952
TI  - New tools for studying osteoarthritis genetics in zebrafish.
AB  - OBJECTIVE: Increasing evidence points to a strong genetic component to
      osteoarthritis (OA) and that certain changes that occur in osteoarthritic
      cartilage recapitulate the developmental process of endochondral ossification. As
      zebrafish are a well validated model for genetic studies and developmental
      biology, our objective was to establish the spatiotemporal expression pattern of
      a number of OA susceptibility genes in the larval zebrafish providing a platform
      for functional studies into the role of these genes in OA. DESIGN: We identified
      the zebrafish homologues for Mcf2l, Gdf5, PthrP/Pthlh, Col9a2, and Col10a1 from
      the Ensembl genome browser. Labelled probes were generated for these genes and in
      situ hybridisations were performed on wild type zebrafish larvae. In addition, we
      generated transgenic reporter lines by modification of bacterial artificial
      chromosomes (BACs) containing full length promoters for col2a1 and col10a1.
      RESULTS: For the first time, we show the spatiotemporal expression pattern of
      Mcf2l. Furthermore, we show that all six putative OA genes are dynamically
      expressed during zebrafish larval development, and that all are expressed in the
      developing skeletal system. Furthermore, we demonstrate that the transgenic
      reporters we have generated for col2a1 and col10a1 can be used to visualise
      chondrocyte hypertrophy in vivo. CONCLUSION: In this study we describe the
      expression pattern of six OA susceptibility genes in zebrafish larvae and the
      generation of two new transgenic lines marking chondrocytes at different stages
      of maturation. Moreover, the tools used demonstrate the utility of the zebrafish
      model for functional studies on genes identified as playing a role in OA.

PMID- 23159954
TI  - The effect of repetitive transcranial magnetic stimulation on fibromyalgia: a
      randomized sham-controlled trial with 1-mo follow-up.
AB  - OBJECTIVES: The aim of this study was to determine whether low-frequency
      repetitive transcranial magnetic stimulation (rTMS) applied to the right
      dorsolateral prefrontal cortex or high-frequency rTMS applied to the left motor
      cortex could influence pain level or mood status in patients with intractable
      fibromyalgia. DESIGN: Fifteen women with fibromyalgia were randomized to low
      frequency (1 Hz), high-frequency (10 Hz), or sham stimulation. The patients
      underwent ten consecutive sessions according to rTMS protocol. The number of
      tender points and the Korean version of the Fibromyalgia Impact Questionnaire
      were used to assess disease status, a visual analog scale was used to measure
      level of pain, and the Beck Depression Inventory was used to assess mood status.
      All subjects were evaluated before, immediately after, and 1 mo after rTMS.
      RESULTS: In the low-frequency group, the Beck Depression Inventory scores
      significantly decreased from baseline to 1 mo after rTMS. The visual analog scale
      and Korean version of the Fibromyalgia Impact Questionnaire scores significantly
      decreased immediately after rTMS. In the high-frequency group, the visual analog
      scale and Beck Depression Inventory scores were significantly decreased
      immediately after rTMS. CONCLUSIONS: Low-frequency rTMS may play a role in the
      long-term treatment of fibromyalgia. Notably, the findings of this study are the
      first to show that the right dorsolateral prefrontal cortex or the left motor
      cortex rTMS could have an antidepressive and pain-modulating effect in patients
      with fibromyalgia.

PMID- 23159955
TI  - Chronic disabling pain: a scotoma in the eye of both pain medicine and
      rehabilitation in Europe.

PMID- 23159956
TI  - Muscle pain in rehabilitation.

PMID- 23159958
TI  - Preparation and in vitro evaluation of plasma-sprayed bioactive akermanite
      coatings.
AB  - Bioactive ceramic coatings on titanium (Ti) alloys play an important role in
      orthopedic applications. In this study, akermanite (Ca(2)MgSi(2)O(7)) bioactive
      coatings are prepared through a plasma spraying technique. The bonding strength
      between the coatings and Ti-6Al-4V substrates is around 38.7-42.2 MPa, which is
      higher than that of plasma sprayed hydroxyapatite (HA) coatings reported
      previously. The prepared akermanite coatings reveal a distinct apatite
      mineralization ability in simulated body fluid. Furthermore, akermanite coatings
      support the attachment and proliferation of rabbit bone marrow mesenchymal stem
      cells (BMSCs). The proliferation rate of BMSCs on akermanite coatings is
      obviously higher than that on HA coatings.

PMID- 23159959
TI  - Low bone mineral density, but not epidural steroid injection, is associated with
      fracture in postmenopausal women with low back pain.
AB  - BACKGROUND: Therapy with glucocorticoids often results in bone loss and
      glucocorticoid-induced osteoporosis. However, the relationship between epidural
      steroid injection (ESI), bone mineral density (BMD), and vertebral fracture
      remains to be determined. OBJECTIVE: To establish a relationship between ESI,
      BMD, and vertebral fracture in postmenopausal women with low back pain. STUDY
      DESIGN: This study was a retrospective, nonblinded, cross-sectional clinical
      study. SETTING: University-based pain management center. METHODS: We reviewed the
      medical records of postmenopausal women with low back pain who were treated with
      ESI. A total of 352 postmenopausal women were divided into 2 groups. Group 1
      consisted of patients without fracture and Group 2 consisted of those with
      fractures. The results of BMD measurements, as well as any fragility fractures,
      the anatomical site involved, and the treatment administered, were also recorded.
      BMD was measured in the lumbar spine, femoral neck, and total femur after the
      treatment. RESULTS: Of the 352 patients, 218 (62%) had no fractures while 134
      (38%) sustained a fracture. The age was significantly higher among patients who
      sustained fractures, and BMD at the lumbar spine, total femur, and femoral neck
      regions was significantly lower among patients who sustained fractures. In each
      region, the prevalence of osteoporosis was significantly higher in patients with
      fracture than in patients without fracture (all P < 0.05). Age, height, and
      weight were associated with low BMD. However, our study showed no consistent
      correlation between BMD and the mean number of ESIs, mean total dose of
      glucocorticoids, or mean duration of ESIs. LIMITATIONS: First, this study is
      limited by the fact that it was retrospective. Second, the number of cases
      receiving very frequent, high-dose glucocorticoid injections was very small.
      CONCLUSIONS: Older age and lower BMD were associated with osteoporotic fracture
      in postmenopausal women treated for low back pain with ESI. The ESIs were not
      associated with low BMD or fracture.

PMID- 23159957
TI  - Interleukin 10 knockout frail mice develop cardiac and vascular dysfunction with
      increased age.
AB  - Cardiovascular dysfunction is a primary independent predictor of age-related
      morbidity and mortality. Frailty is associated with activation of inflammatory
      pathways and fatigue that commonly presents and progresses with age. Interleukin
      10 (IL-10), the cytokine synthesis inhibitory factor, is an anti-inflammatory
      cytokine produced by immune and non-immune cells. Homozygous deletion of IL-10 in
      mice yields a phenotype that is consistent with human frailty, including age
      related increases in serum inflammatory mediators, muscular weakness, higher
      levels of IGF-1 at midlife, and early mortality. While emerging evidence suggests
      a role for IL-10 in vascular protection, a clear mechanism has not yet been
      elucidated. METHODS: In order to evaluate the role of IL-10 in maintenance of
      vascular function, force tension myography was utilized to access ex-vivo
      endothelium dependent vasorelaxation in vessels isolated from IL-10 knockout IL
      10(tm/tm) and control mice. Pulse wave velocity ((PWV), index of stiffness) of
      vasculature was measured using ultrasound and blood pressure was measured using
      the tail cuff method. Echocardiography was used to elucidated structure and
      functional changes in the heart. RESULTS: Mean arterial pressures were
      significantly higher in IL-10(tm/tm) mice as compared to C57BL6/wild type (WT)
      controls. PWV was increased in IL-10(tm/tm) indicating stiffer vasculature.
      Endothelial intact aortic rings isolated from IL-10(tm/tm) mice demonstrated
      impaired vasodilation at low acetylcholine doses and vasoconstriction at higher
      doses whereas vasorelaxation responses were preserved in rings from WT mice.
      Cyclo-oxygenase (COX-2)/thromboxane A2 inhibitors improved endothelial dependent
      vasorelaxation and reversed vasoconstriction. Left ventricular end systolic
      diameter, left ventricular mass, isovolumic relaxation time, fractional
      shortening and ejection fraction were all significantly different in the aged IL
      10(tm/tm) mice compared to WT mice. CONCLUSION: Aged IL-10(tm/tm) mice have
      stiffer vessels and decreased vascular relaxation due to an increase in
      eicosanoids, specifically COX-2 activity and resultant thromboxane A2 receptor
      activation. Our results also suggest that aging IL-10(tm/tm) mice have an
      increased heart size and impaired cardiac function compared to age-matched WT
      mice. While further studies will be necessary to determine if this age-related
      phenotype develops as a result of inflammatory pathway activation or lack of IL
      10, it is essential for maintaining the vascular compliance and endothelial
      function during the aging process. Given that a similar cardiovascular phenotype
      is present in frail, older adults, these findings further support the utility of
      the IL-10(tm/tm) mouse as a model of frailty.

PMID- 23159960
TI  - Study of percutaneous lumbar decompression and treatment algorithm for patients
      suffering from neurogenic claudication.
AB  - BACKGROUND: Symptomatic lumbar spinal stenosis (LSS) patients often suffer from
      multiple etiologies, and patient symptoms must be differentiated and identified
      as either neurogenic claudication, radicular pain, or both. The most common
      symptom associated with LSS is neurogenic claudication, which has been reported
      to occur in 91% to 100% of the LSS patient population. Neurogenic claudication
      symptoms are described as pain radiating to the lower extremities that begins and
      worsens as the patient ambulates. Neurogenic claudication symptoms worsen over
      time and can eventually result in significant life-altering functional
      limitations. Symptomatic LSS patients may also suffer from radicular pain, which
      is a persistent pain transmitted through neural pathways, and is associated with
      inflammation of the exiting nerve root. OBJECTIVE: To assess patient safety, pain
      reduction, and functional status of patients treated with percutaneous lumbar
      decompression. STUDY DESIGN: Single-center, prospective clinical study of 46
      consecutive patients with neurogenic claudication symptoms related to lumbar
      spinal stenosis. SETTING: US interventional pain management practice. METHODS:
      From March 2010 to January 2011, 46 LSS patients suffering from neurogenic
      claudication underwent mild percutaneous lumbar decompression. Of these, 12-week,
      6-month and one-year follow-up was available for 35 patients. OUTCOME ASSESSMENT:
      Visual Analog Scale (VAS), Oswestry Disability Index (ODI), and Zurich
      Claudication Questionnaire (ZCQ). Outcomes were assessed at baseline, 12-week, 6
      month and one-year follow-ups. RESULTS: One-year follow-up patients in this study
      experienced statistically and clinically significant improvement in physical
      function, as well as reduction of pain intensity. The initial improvement in
      these patients, which was significant, was sustained through one year, with no
      significant differences among the interim follow-up visit periods. These results
      demonstrate early improvement following treatment with a high degree of
      durability over time. There were no serious device or procedure-related
      complications reported in this study. LIMITATIONS: Single-center study with no
      control group. CONCLUSIONS: In this study, the mild procedure was shown to be
      safe. In addition, patients experienced significant improvement in mobility and
      reduction of pain one year after the procedure. One-year outcomes were not
      significantly different from interim results, indicating that the significant
      improvement following treatment, occurring as early as 12 weeks, was maintained
      through one year. This high degree of consistency over time indicates the
      durability of percutaneous lumbar decompression in the treatment of neurogenic
      claudication in symptomatic LSS.

PMID- 23159961
TI  - Salivary cortisol concentration changes after epidural steroid injection.
AB  - BACKGROUND: Epidural steroid injections (ESI) are therapeutically useful for the
      treatment of herniated intervertebral discs and spinal stenosis. However, there
      is a lack of evidence-based data about the safety of steroids. OBJECTIVES: The
      aim of this study was to determine the period of hypothalamus-pituitary-adrenal
      (HPA) axis suppression by salivary cortisol measurements after a single epidural
      injection of 40 mg of triamcinolone. STUDY DESIGN: Clinical observational pilot
      study. SETTING: Outpatient follow-up. METHODS: In this study, 8 patients with
      lumbar intervertebral disc herniation or spinal stenosis were enrolled. All
      patients had received ESI (triamcinolone 40 mg) under C-arm guidance. Salivary
      cortisol concentrations were assessed between 8:00 am and 9:00 am; both before
      and after ESI (Day 0 [the day prior to injection], 1, 3, 5, 7, 14, 21, 28).
      Additionally, body weight, blood pressure, 0-10 numeric rating scale (NRS), and
      fasting blood sugar levels were evaluated. RESULTS: HPA axis suppression was
      observed in all patients for 19.9 +/- 6.8 days after ESI (salivary cortisol < 0.1
      ug/mL). In total, 5 of 8 patients reached baseline salivary cortisol
      concentrations within the clinical trial period. The time taken to reach baseline
      concentrations after ESI was 19.4 +/- 8.3 days. The period of HPA axis
      suppression was not correlated with baseline salivary cortisol concentrations,
      and NRS scores. LIMITATIONS: Adrenal insufficiency cannot be confirmed by simple
      salivary cortisol measurements. Furthermore, the period studied was too short for
      all patients' HPA axis function to reach the baseline value. Finally, the study
      design does not allow for the confounding effects of pain and stress on cortisol
      levels. CONCLUSIONS: HPA axis function was suppressed after ESI until Day 21 and
      returned to the normal range after 19.9 +/- 6.8 days. Therefore, we suggest that
      the minimal interval between ESI treatments should be at least one month. In
      addition, we report that salivary cortisol measurements are very useful
      diagnostic predictors of HPA function.

PMID- 23159962
TI  - Effect of early stellate ganglion blockade for facial pain from acute herpes
      zoster and incidence of postherpetic neuralgia.
AB  - BACKGROUND: The incidence of postherpetic neuralgia (PHN) has been reported to be
      25% among those over the age of 50 years treated with antiviral medication. The
      role of sympathetic block in its prevention remains questionable. OBJECTIVES: The
      aim of this study is to determine whether early stellate ganglion blockade for
      acute herpes zoster of the face will reduce the intensity and duration of acute
      herpetic pain, and if the blockade has the potential to prevent or reduce the
      incidence and/or severity of PHN. STUDY DESIGN: Randomized, controlled, double
      blind trial. SETTING: Hospital, outpatient setting. METHODS: Sixty-four patients
      over 50 years were assigned to receive a stellate ganglion block using either 8
      mL saline (Group 1) or 6 mL bupivacaine 0.125% and 8 mg dexamethasone in a total
      volume of 8 mL (Group 2). All procedures were performed under fluoroscopy. All
      patients received pregabalin in a dose of 150 mg twice daily. Acetaminophen was
      available as needed. Pain assessment using the visual analog scale and amount of
      analgesic being taken was measured at the initial visit (basal), weekly for 6
      weeks after the procedure and after 2, 3, and 6 months. Once a patient reported
      mild pain during the trial, pregabalin was tapered by 75 mg every other day; the
      patients who succeeded in this step were recorded in each group. The time of
      complete resolution of pain and incidence of persistent postherpetic pain was
      reported. Each patient's satisfaction was evaluated. RESULTS: There was a
      significantly shorter duration of pain noticed in Group 2 (P = 0.002). A
      significantly lower incidence of PHN was encountered in Group 2 after 3 months (P
      = 0.043) and 6 months (P = 0.035). Significantly more patient satisfaction was
      reported in Group 2 after 3 and 6 months. By the fourth week, 29 patients in
      Group 2 reported no pain. Two patients reported mild pain after 3 months which
      was resolved by the sixth month. In Group 1, 22 patients reported no pain by the
      sixth week and 8 patients reported moderate pain after 2 and 3 months; by the
      sixth month, 4 out of those 8 patients showed spontaneous remission of pain.
      There was a significant reduction in the total doses of pregabalin and
      acetaminophen in Group 2 (P < 0.001). No serious adverse effects were reported
      during the study period. LIMITATIONS: The sample size was determined using the
      incidence of PHN (chronic pain) as a main hypothesis. Meanwhile, this study
      determined the incidence of acute pain as well, which may lead to bias to the
      results of acute pain. CONCLUSION: Early stellate ganglion blockade, in
      combination with an antiviral agent, is a very effective treatment modality; it
      dramatically decreases the intensity of acute pain and shortens its duration and
      reduces the incidence of postherpetic neuralgia.

PMID- 23159963
TI  - SynchroMed II intrathecal pump memory errors due to repeated magnetic resonance
      imaging.
AB  - Cancer patients with severe refractory pain are often managed with implantable
      drug delivery systems (IDDS). The only drugs with US Food and Drug Administration
      approval for intrathecal use are morphine, ziconotide, and baclofen. Other drugs
      used and mixed include, hydromorphone, bupivacaine, sufentanil, and fentanyl.
      These patients often undergo magnetic resonance imaging (MRI) for disease-related
      monitoring and diagnoses. Although uncommon, IDDS can fail to resume normal
      functioning after MRI, potentially causing complications. The magnetic field of
      an MRI will temporarily stop the rotor of the pump motor and suspend drug
      delivery for the duration of the MRI exposure. The pump should resume normal
      operation when removed from the MRI magnetic field, but there is a potential for
      a delay in the return of proper drug infusion and a delay in the logging of motor
      stall events after an MRI in the SynchroMed II pumps. A 57-year-old man who
      underwent multiple MRIs with an implanted IDDS experienced 2 separate memory
      failures leading to multiple complications. After the first pump malfunction, the
      patient developed withdrawal symptoms and was treated in the emergency
      department. The first time, a memory reset resolved the problem. The second time,
      29 months later, the patient was admitted to the hospital to manage withdrawal
      symptoms and the pump had to be exchanged with a new device. Post-MRI pump
      interrogation should be performed on all patients with IDDS to ensure proper
      functioning of the pump. Special attention should be paid to patients receiving
      baclofen, as acute withdrawal can be very serious, even deadly.

PMID- 23159964
TI  - Use of eptifibatide as a bridge antiplatelet agent for intrathecal drug delivery
      system placement.
AB  - Use of antiplatelet agents is becoming increasingly common, and their management
      may require new strategies if neuroaxial techniques are to be employed in
      patients who will not tolerate discontinuation of antiplatelet therapy. The
      patient was a 46-year-old man with a past medical history significant for
      coronary artery disease and who had undergone 14 stents. He developed stent
      thrombosis (ST) while on clopidogrel. Following the ST, he was subsequently
      placed on prasugrel. While on prasugrel, the patient presented for an intrathecal
      drug delivery system (IDDS) trial and placement due to severe peripheral
      neuropathy unresponsive to several conservative medical treatments. He had
      previously undergone an unsuccessful spinal cord stimulator trial and received no
      pain relief. In consultation with his outside cardiologist, the patient received
      permission to hold his prasugrel for 7 days prior to his intrathecal pump trial.
      During the trial period's inpatient hospitalization, the patient developed chest
      pain. In consultation with the cardiology service in our institution, it was
      decided antiplatelet therapy should be re-instituted. The patient was bridged to
      his IDDS placement after the trial with intravenous eptifibatide. The
      eptifibatide drip was administered 6 hours prior to the IDDS implant. Functional
      platelet count was checked one hour before the IDDS was placed and the pump was
      placed without incident. The eptifibatide drip was reinstituted one hour after
      the IDDS implantation. The patient was observed for 24 hours on the eptifibatide
      drip, transitioned to his home dose of prasugrel, and discharged home. At
      outpatient follow-up one week later, the patient demonstrated no neurologic or
      hemorrhagic complications and was satisfied with the pain control provided by the
      IDDS. Prasugrel is an irreversible platelet inhibitor, which prevents ADP-induced
      platelet aggregation by binding the P2Y12 receptor. Patients taking prasugrel
      will have deficient platelet activity until new platelets have been produced, a
      span of approximately 7 days. Eptifibatide is an intravenous glycoprotein
      IIb/IIIa inhibitor with a short half-life of 1/2 hours. Inhibition of
      glycoprotein IIb/IIIa prevents platelet activation and aggregation. The drug
      effect ceases once it is discontinued and restoration of platelet function is not
      dependent upon new platelet production. Patients requiring antiplatelet therapy
      in need of neuroaxial pain management procedures present challenging problems to
      pain management physicians. Current guidelines from the American Society of
      Regional Anesthesia have not identified any bridging agent suitable for patients
      who may not tolerate prolonged withdrawal from their antiplatelet therapy. In
      this case, eptifibatide was successfully utilized to bridge a patient whose
      comorbid conditions necessitated continuous antiplatelet therapy without the
      prolonged washout common to irreversible antiplatelet agents.

PMID- 23159965
TI  - Topical amitriptyline-ketamine for treatment of rectal, genital, and perineal
      pain and discomfort.
AB  - BACKGROUND: Pain in the rectal, genital, and perineal area is a common condition
      treated by pain physicians. These chronic pain syndromes are therapeutically
      challenging because both interventional and drug therapies often are ineffective.
      OBJECTIVES: To determine if pelvic pain can be treated effectively with
      compounded topical amitriptyline-ketamine. STUDY DESIGN: A retrospective review
      of medical records. SETTING: A single academic medical center in the United
      States. METHODS: We identified all patients treated with topical amitriptyline
      ketamine from January 1, 2004, through November 28, 2011. Medical records were
      evaluated to determine the diagnosis for which the medication was prescribed.
      Treatment efficacy and any adverse effects were recorded. RESULTS: Of the 1,068
      patients who received amitriptyline-ketamine, 13 had the medication prescribed
      for genital, rectal, or perineal pain and had medication efficacy recorded. Of
      these 13 patients, one (8%) had complete relief, 6 (46%) had substantial relief,
      4 (31%) had some relief, and 2 (15%) had no response. One patient reported
      occasional irritation while using topical amitriptyline-ketamine with lidocaine;
      no other patients reported local or systemic adverse effects. LIMITATIONS:
      Retrospective review; lack of uniform system for pain grading; concurrent use of
      other medications. CONCLUSIONS: Topical amitriptyline-ketamine provided a high
      rate of pain relief with a low adverse-effect burden in patients with pelvic
      pain. This topical medication could offer an effective, noninvasive, nonopioid
      therapy for pain in the rectum, perineum, and genitals.

PMID- 23159966
TI  - Iatrogenic hypercortisolism complicating triamcinolone acetonide injections in
      patients with HIV on ritonavir-boosted protease inhibitors.
AB  - Epidural corticosteroid injection is a commonly used approach for managing back
      pain of several etiologies. The risk of clinical complications from systemic
      absorption is felt to be rare. Ritonavir is a protease inhibitor whose potent
      cytochrome P450 3A4 inhibition is exploited for pharmacologic boosting in human
      immunodeficiency virus (HIV) infection. It has been associated with systemic
      hypercortisolism when used in combination with nasal and inhaled corticosteroids.
      This is a case series describing 2 patients with HIV on ritonavir-containing
      regimens who developed iatrogenic hypercortisolism following epidural injection
      of triamcinolone acetonide. The 2 patients developed cushingoid symptoms, with
      detectable serum triamcinolone acetonide levels weeks after their epidural
      injections. Their symptoms took several weeks to resolve, in one case
      necessitating a change to an HIV regimen that did not contain ritonavir. 
      Iatrogenic hypercortisolism is a rarely reported, but potentially devastating
      complication of injectable corticosteroids. Individuals receiving ritonavir-based
      therapy appear to be at increased risk for this process due to pharmacologic
      boosting of the corticosteroid. The preponderance of reported cases of iatrogenic
      hypercortisolism following injectable corticosteroids has involved triamcinolone
      acetonide, which may be due to the relatively rapid absorption characteristics
      and high serum levels of this compound compared with other preparations. For
      individuals on ritonavir-containing HIV therapy, we recommend close coordination
      with the involved HIV clinicians prior to use of injectable corticosteroids, and
      avoidance of injections with triamcinolone acetonide whenever possible. Choosing
      an alternative corticosteroid preparation to triamcinolone acetonide may reduce
      the risk of systemic absorption, though more research is needed to confirm this
      hypothesis.

PMID- 23159967
TI  - The effect of Helicobacter pylori eradication on migraine: a randomized, double
      blind, controlled trial.
AB  - BACKGROUND: Recent studies have shown a positive correlation between Helicobacter
      pylori (H. pylori)infection and migraine headache. OBJECTIVE: To study the impact
      of H. pylori eradication on migraine headache. STUDY DESIGN: Double blind,
      randomized, controlled clinical trial. SETTING: Sixty-four patients diagnosed
      with migraine-type headache were included in the study. The patients were
      randomly allocated into 2 groups: a treatment group that received migraine
      treatment and H.pylori eradication treatment, and a control group that received
      migraine treatment and a placebo in place of H. pylori eradication treatment.
      METHODS: There were 25 women and 7 men in the treatment group and 22 women and 10
      men in the control group. The MIDAS (Migraine Disability Assessment)
      questionnaire was used to assess the severity of symptoms, before and after
      treatment. RESULT: There was no significant difference between treatment group
      patients and control group patients with respect to age (44.6 +/- 8.8 vs. 43.8 +/
      13.8), clinical symptoms and signs. In the beginning of the study, patients in
      the treatment group had a higher MIDAS compared to patients in the control group
      (28.87 +/- 6.18 vs. 25.43 +/- 7.13, P < 0.05). There was no significant
      difference between the treatment and control groups, with respect to the MIDAS,
      after treatment (20.09 +/- 1.14 vs. 20.00 +/- 1.150, P = 0.5). General linear
      model, repeated measures demonstrated that the reduction in the MIDAS score was
      more prominent in the treatment group (Mean Square 164.25, F: 2.02, P = 0.05).
      LIMITATIONS: Short-term follow up. CONCLUSION: H. pylori eradication may have a
      beneficial role on migraine headache. This shows the significance of H. pylori
      treatment in the management of migraine headache among Iranian patients.

PMID- 23159968
TI  - IL-7, IL-18, MCP-1, MIP1-beta, and OPG as biomarkers for pain treatment response
      in patients with cancer.
AB  - BACKGROUND: Pain is one of the most common symptoms in patients suffering from
      advanced cancer and receiving palliative care and is often responsible for a poor
      quality of life. To date, there exists no published correlation between
      biological, measurable biomarkers and pain intensity. OBJECTIVES: The primary
      objective was to search and identify pain-associated cytokines (biomarkers)
      correlating with changes in numeric rating scale (NRS) pain scores in patients
      with cancer before and after pain treatment. The secondary objectives were to
      assess cytokine serum level differences between patients and healthy controls and
      to evaluate possible relationships between pain entities, pain intensity (in
      NRS), gender, location of primary tumor, and the patients' cytokine baseline
      concentrations. STUDY DESIGN: Controlled, prospective study. SETTING: University
      medical center. METHODS: Eligible patients with exacerbated cancer-related pain
      (NRS = 5) and healthy controls with no pain were included. Serum level changes of
      19 cytokines were analyzed before and during opioid treatment. RESULTS: Of 19
      analyzed biomarkers, 5 (IL-7, IL-18, MCP-1, MIP-1alpha, MIP-1beta and OPG) turned
      out to correlate significantly with pain relief. In healthy controls, all
      analyzed cytokines showed no significant differences. In the secondary analysis,
      only one significant correlation was detected between OPG and pain entities.
      Furthermore, IL-4, IL-7, IFN-gamma and OPG appeared to account for the ability to
      predict a patient's gender. LIMITATIONS: Our findings should be considered as
      preliminary and need to be confirmed in further studies. CONCLUSION: Our results
      provide preliminary evidence of a significant correlation of pain relief in
      patients with cancer and at least 5 cytokines. These biomarkers may serve as the
      basis for development of diagnostic tools for pain assessment and could serve as
      potential new targets for pain control.

PMID- 23159969
TI  - Spinal cord stimulation for chronic pain originating from Lyme disease.
AB  - BACKGROUND: Neuropathic pain is a relatively common outcome of Lyme disease. Pain
      management options for these patients have been limited to pharmaceutical
      treatments. OBJECTIVE: We present a case of chronic pain following Lyme disease
      treated successfully using spinal cord stimulation (SCS). STUDY DESIGN: Case
      report. SETTING: Pain management clinic. METHODS: A 62-year-old patient presented
      with a 5-year history of bilateral foot pain following Lyme disease that failed
      to respond to medication and physical therapy. The patient was treated by a trial
      of SCS at the clinic and then implanted with a spinal cord stimulator. The Visual
      Analog Scale (VAS) assessed pain before and after SCS. RESULTS: The patient
      reported significant pain relief and improved foot function. The 10 point VAS
      score was reduced from 8-10 to 1-3. LIMITATIONS: Single case report. CONCLUSION:
      Spinal cord stimulation may be an effective option for relieving chronic pain
      originating from Lyme disease.

PMID- 23159970
TI  - Digital subtraction angiography does not reliably prevent paraplegia associated
      with lumbar transforaminal epidural steroid injection.
AB  - Digital subtraction angiography (DSA) has been touted as a radiologic adjunct to
      interventional neuraxial procedures where it is imperative to identify vascular
      compromise during the injection. Transforaminal epidural steroid injections
      (TFESI) are commonly performed interventions for treating acute and chronic
      radicular spine pain. We present a case of instantaneous and irreversible
      paraplegia following lumbar TFESI wherein a local anesthetic test dose, as well
      as DSA, were used as adjuncts to fluoroscopy. An 80-year-old man with severe
      lumbar spinal stenosis and chronic L5 radiculopathic pain was evaluated at a
      university pain management center seeking symptomatic pain relief. Two prior
      lumbar interlaminar epidural steroid injections (LESI) provided only transient
      pain relief, and a decision was made to perform right-sided L5-S1 TFESI. A 5
      inch, 22-gauge Quincke-type spinal needle with a curved tip was used. Foraminal
      placement of the needle tip was confirmed with anteroposterior, oblique, and
      lateral views on fluoroscopy. Aspiration did not reveal any blood or
      cerebrospinal fluid. Digital subtraction angiography was performed twice to
      confirm the absence of intravascular contrast medium spread. Subsequently, a 0.5
      mL of 1% lidocaine test dose was performed without any changes in neurological
      status. Two minutes later, a mixture of one mL of 1% lidocaine with 80 mg
      triamcinolone acetonide was injected. Immediately following the completion of the
      injection, the patient reported extreme bilateral lower extremity pain. He became
      diaphoretic, followed by marked weakness in his bilateral lower extremities and
      numbness up to his lower abdomen. The patient was transferred to the emergency
      department for evaluation. Magnetic resonance imaging (MRI) of the lumbar and
      thoracic spine was completed 5 hours postinjection. It showed a small high T2
      signal focus in the thoracic spinal cord at the T7-T8 level. The patient was
      admitted to the critical care unit for neurological observation and treatment
      with intravenous methylprednisolone. Follow-up MRI revealed a hyper-intense T2
      and short-tau inversion recovery signal in the central portion of the spinal cord
      beginning at the level of the T6 superior endplate and extending caudally to the
      T9-T10 level with accompanying development of mild spinal cord expansion. The
      patient was diagnosed with paraplegia from acute spinal cord infarction. At
      discharge to an acute inpatient rehabilitation program, the patient had
      persistent bilateral lower extremity paralysis, and incontinence of bowel and
      bladder functions. In the present patient, DSA performed twice and an anesthetic
      test dose did not prevent a catastrophic spinal cord infarction and resulting
      paraplegia. DSA use is clearly not foolproof and may not be sufficient to
      identify potentially life-or-limb threatening consequences of lumbar TFESI. We
      believe that this report should open further discussion regarding adding the
      possibility of these catastrophic events in the informed consent process for
      lumbar TFESIs, as it has for cervical TFESI. Utilizing blunt needles or larger
      bevel needles in place of sharp, cutting needles may minimize the chances of this
      event occurring. Considering eliminating use of particulate steroids for TFESI
      should be evaluated, although the use of nonparticulate agents remains
      controversial due to the perception that their respective duration of action is
      less than that of particulate steroids.

PMID- 23159971
TI  - Prospective clinical study on natural history of discogenic low back pain at 4
      years of follow-up.
AB  - BACKGROUND: To accurately assess the effect of any therapy for treating
      discogenic low back pain, the natural history of such pain should be known
      beforehand. However, until now, no pathological characteristic could be used to
      predict the disease course of low back pain. OBJECTIVE: To better instruct the
      clinical treatment of discogenic low back pain, a prospective clinical study was
      performed to observe the natural history of the disease. STUDY DESIGN: A
      prospective clinical study during a 4-year follow-up period. SETTING: The study
      was performed at a spinal center in China. METHODS: A total of 279 patients with
      chronic low back pain were included from June 2006 through October 2007. Using
      discography, 156 patients (56%) were diagnosed to have discogenic back pain. A
      101-point numerical rating scale (NRS) was used to assess the back pain symptoms
      and the Oswestry Disability Index (ODI) was used to assess lumbar function.
      RESULTS: Of the 156 patients, 131 (84%) completed the study at 4-year follow-up.
      At the end of follow-up, 17 patients (13.0%) had their low back pain symptoms
      alleviated and lumbar function improved; 10 patients (7.6%) were slightly
      improved; 16 patients (12.2%) had their symptoms aggravated; and 88 patients
      (67.2%) experienced the same pain and disability as before. Although the average
      NRS and ODI scores obtained during the 4-year follow-up study gradually
      decreased, statistical significances were found in such changes (P < 0.05,and P <
      0.05, respectively); however, the improvement rates of both pain (7.6%) and
      disability (5.2%) were very low. LIMITATIONS: The shortcoming of this study is
      its relatively small sample size. CONCLUSION: The present study indicated that
      the natural history of discogenic low back pain was chronic but persistent, and
      that the pain and disability in most patients did not improve over time.

PMID- 23159972
TI  - The major efficient mechanisms of ozone therapy are obtained in intradiscal
      procedures.

PMID- 23159973
TI  - Obtaining more information from the sacroiliac joint arthrogram.

PMID- 23159975
TI  - An update of the appraisal of the accuracy of thoracic discography as a
      diagnostic test for chronic spinal pain.
AB  - BACKGROUND: Even though the prevalence of thoracic pain has been reported to be
      13% of the general population and up to 22% of the population in interventional
      pain management settings, the role of thoracic discs as a cause of chronic
      thoracic and extrathoracic pain has not been well studied. The intervertebral
      discs, zygapophysial or facet joints, and other structures including the
      costovertebral and costotransverse joints have been identified as a source of
      thoracic pain. STUDY DESIGN: A systematic review of provocation thoracic
      discography. OBJECTIVE: To systematically assess and update the quality of
      clinical studies evaluating the diagnostic accuracy of provocation thoracic
      discography. METHODS: A systematic review of the literature was performed to
      assess the diagnostic accuracy of thoracic discography with respect to chronic,
      function limiting, thoracic or extrathoracic pain. The available literature on
      thoracic discography was reviewed. A methodological quality assessment of
      included studies was performed using Quality Appraisal of Reliability Studies
      (QAREL). 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). Data sources included relevant literature identified through
      searches of PubMed and EMBASE from 1966 to June 2012, and manual searches of the
      bibliographies of known primary and review articles. RESULTS: The evidence and
      clinical value of thoracic provocation discography is limited (poor) with a
      paucity of evidence, with only 2 studies meeting inclusion criteria. LIMITATIONS:
      The limitation of this study continues to be the paucity of literature.
      CONCLUSION: Based on the available evidence for this systematic review, due to
      limited evidence, thoracic provocation discography is rarely recommended for the
      diagnosis of discogenic pain in the thoracic spine, if conservative management
      has failed and facet joint pain has been excluded.

PMID- 23159976
TI  - An update of the appraisal of the accuracy and utility of cervical discography in
      chronic neck pain.
AB  - BACKGROUND: Chronic neck pain represents a significant public health problem.
      Despite high prevalence rates, there is a lack of consensus regarding the causes
      or treatments for this condition. Based on controlled evaluations, the cervical
      intervertebral discs, facet joints, and atlantoaxial joints have all been
      implicated as pain generators. Cervical provocation discography, which includes
      disc stimulation and morphological evaluation, is occasionally used to
      distinguish a painful disc from other potential sources of pain. Yet in the
      absence of validation and controlled outcome studies, the procedure remains mired
      in controversy. STUDY DESIGN: A systematic review of the diagnostic accuracy of
      cervical discography. OBJECTIVE: To systematically evaluate and update the
      diagnostic accuracy of cervical discography. METHODS: The available literature on
      cervical discography was reviewed. Methodological quality assessment of included
      studies was performed using Quality Appraisal of Reliability Studies (QAREL).
      Only diagnostic accuracy studies meeting at least 50% of the designated inclusion
      criteria were utilized for analysis. However, studies scoring less than 50% are
      presented descriptively and analyzed critically. 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).Data sources
      included relevant literature identified through searches of PubMed and EMBASE
      from 1966 to June 2012, and manual searches of the bibliographies of known
      primary and review articles. RESULTS: A total of 41 manuscripts were considered
      for accuracy and utility of cervical discography in chronic neck pain. There were
      23 studies evaluating accuracy of discography. There were 3 studies meeting
      inclusion criteria for assessing the accuracy and prevalence of discography, with
      a prevalence of 16% to 53%. Based on modified Agency for Healthcare Research and
      Quality (AHRQ) accuracy evaluation and United States Preventive Services Task
      Force (USPSTF) level of evidence criteria, this systematic review indicates the
      strength of evidence is limited for the diagnostic accuracy of cervical
      discography. LIMITATIONS: Limitations include a paucity of literature, poor
      methodological quality, and very few studies performed utilizing International
      Association for the Study of Pain (IASP) criteria. CONCLUSION: There is limited
      evidence for the diagnostic accuracy of cervical discography. Nevertheless, in
      the absence of any other means to establish a relationship between pathology and
      symptoms, cervical provocation discography may be an important evaluation tool in
      certain contexts to identify a subset of patients with chronic neck pain
      secondary to intervertebral disc disorders. Based on the current systematic
      review, cervical provocation discography performed according to the IASP criteria
      with control disc(s), and a minimum provoked pain intensity of 7 of 10, or at
      least 70% reproduction of worst pain (i.e. worst spontaneous pain of 7 = 7 x 70%
      = 5), may be a useful tool for evaluating chronic pain and cervical disc
      abnormalities in a small proportion of patients.

PMID- 23159977
TI  - An updated review of the diagnostic utility of cervical facet joint injections.
AB  - BACKGROUND: Chronic persistent neck pain with or without upper extremity pain is
      common in the general adult population with a prevalence of 48% for women and 38%
      for men, with persistent complaints in 22% of women and 16% of men. Multiple
      modalities of treatment are exploding in managing chronic neck pain along with
      increasing prevalence. However, there is a paucity of evidence for all modalities
      of treatments in managing chronic neck pain. Controlled studies have supported
      the existence of cervical facet or zygapophysial joint pain in 36% to 60% in
      heterogenous population of these patients. However, these studies also have shown
      false-positive results in 27% to 63% of patients with a single diagnostic block.
      STUDY DESIGN: A systematic review of diagnostic cervical facet joint nerve
      blocks. OBJECTIVE: To evaluate and update the accuracy of diagnostic facet joint
      nerve blocks in the diagnosis of facet joint pain. METHODS: A methodological
      quality assessment of included studies was performed using Quality Appraisal of
      Reliability Studies (QAREL). Only diagnostic accuracy studies meeting at least
      50% of the designated inclusion criteria were utilized for analysis. Studies
      scoring less than 50% are presented descriptively and critically analyzed. The
      level of evidence was classified as good, fair, and limited or poor based on the
      quality of evidence developed by the United States Preventive Services Task Force
      (USPSTF).Data sources included relevant literature identified through searches of
      PubMed and EMBASE from 1966 to June 2012, and manual searches of the
      bibliographies of known primary and review articles. RESULTS: Overall, a total of
      26 manuscripts were considered for diagnostic accuracy evaluation and 9
      manuscripts for studies evaluating various factors influencing the diagnostic
      validity of facet joint interventions. Based on 9 studies meeting the inclusion
      criteria utilizing 75% to 100% pain relief as the criterion standard with
      controlled blocks, the evidence is good for diagnostic accuracy of cervical facet
      joint pain, with a prevalence of 36% to 60% with a false-positive rate of 27% to
      63% with a single block. Based on 2 studies from the same group of authors, the
      evidence for 75% to 100% pain relief as the criterion standard with a single
      block is limited. The evidence is limited for a single diagnostic block with 50%
      to 74% pain relief as the criterion standard, whereas no studies were available
      assessing the accuracy of 50% to 74% pain relief as the criterion standard with
      controlled blocks. LIMITATIONS: The limitations of this systematic review include
      a paucity of literature on outcomes, randomized, placebo-controlled trials and a
      lack of consensus on a gold standard. CONCLUSIONS: Diagnostic cervical facet
      joint nerve blocks are safe, valid, and reliable. The strength of evidence for
      diagnostic facet joint nerve blocks is good with the utilization of controlled
      diagnostic blocks with at least 75% pain relief as the criterion standard;
      however, the evidence is limited for single blocks or dual blocks for relief of
      50% to 74% and single blocks with at least 75% pain relief.

PMID- 23159978
TI  - Systematic review of the therapeutic effectiveness of cervical facet joint
      interventions: an update.
AB  - BACKGROUND: The prevalence of chronic, recurrent neck pain is approximately 15%
      of the adult general population. Controlled studies have supported the existence
      of cervical facet or zygapophysial joint pain in 36% to 67% of these patients,
      when disc herniation, radiculitis, and discogenic are not pathognomic. However,
      these studies also have shown false-positive results in 27% to 63% of the
      patients with a single diagnostic block. There is also a paucity of literature
      investigating therapeutic interventions of cervical facet joint pain. STUDY
      DESIGN: Systematic review of therapeutic cervical facet joint interventions.
      OBJECTIVE: To determine and update the clinical utility of therapeutic cervical
      facet joint interventions in the management of chronic neck pain. METHODS: The
      available literature for utility of facet joint interventions in therapeutic
      management of cervical facet joint pain was reviewed. The quality assessment and
      clinical relevance criteria utilized were the Cochrane Musculoskeletal Review
      Group criteria as utilized for interventional techniques for randomized trials
      and the criteria developed by the Newcastle-Ottawa Scale criteria for
      observational studies. 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). Data sources included relevant literature
      identified through searches of PubMed and EMBASE from 1966 to June 2012, and
      manual searches of the bibliographies of known primary and review articles.
      OUTCOME MEASURES: The primary outcome measure was pain relief (short-term relief
      = up to 6 months and long-term > 6 months). Secondary outcome measures were
      improvement in functional status, psychological status, return to work, and
      reduction in opioid intake. RESULTS: In this systematic review, 32 manuscripts
      were considered for inclusion. For final analysis, 4 randomized trials and 6
      observational studies met the inclusion criteria and were included in the
      evidence synthesis. Based on one randomized, sham-controlled, double-blind trial
      and 5 observational studies, the indicated evidence for cervical radiofrequency
      neurotomy is fair. Based on one randomized, double-blind, active-controlled trial
      and one prospective evaluation, the indicated evidence for cervical medial branch
      blocks is fair. Based on 2 randomized controlled trials, the evidence for
      cervical intraarticular injections is limited. LIMITATIONS: Paucity of the
      overall published literature and specifically lack of literature for
      intraarticular cervical facet joint injections. CONCLUSIONS: The indicated
      evidence for cervical radiofrequency neurotomy is fair. The indicated evidence
      for cervical medial branch blocks is fair. The indicated evidence for cervical
      intraarticular injections with local anesthetic and steroids is limited.

PMID- 23159979
TI  - An update of the systematic assessment of the diagnostic accuracy of lumbar facet
      joint nerve blocks.
AB  - BACKGROUND: Lumbar facet joints are a well recognized source of low back pain and
      referred pain in the lower extremity in patients with chronic low back pain.
      Conventional clinical features and other non-invasive diagnostic modalities are
      unreliable in diagnosing lumbar zygapophysial joint pain. Controlled diagnostic
      studies with at least 80% pain relief as the criterion standard have shown the
      prevalence of lumbar facet joint pain to be 16% to 41% of patients with chronic
      low back pain without disc displacement or radiculitis, with a false-positive
      rate of 17% to 49% with a single diagnostic block. STUDY DESIGN: A systematic
      review of the diagnostic accuracy of lumbar facet joint nerve blocks. OBJECTIVE:
      To determine and update the diagnostic accuracy of lumbar facet joint nerve
      blocks in the assessment of chronic low back pain. METHODS: A methodological
      quality assessment of included studies was performed using Quality Appraisal of
      Reliability Studies (QAREL). Only diagnostic accuracy studies meeting at least
      50% of the designated inclusion criteria were utilized for analysis. Studies
      scoring less than 50% are presented descriptively and analyzed critically. The
      level of evidence was classified as good, fair, and limited or poor based on the
      quality of evidence developed by the United States Preventive Services Task Force
      (USPSTF). Data sources included relevant literature identified through searches
      of PubMed and EMBASE from 1966 to June 2012, and manual searches of the
      bibliographies of known primary and review articles. OUTCOME MEASURES: Studies
      must have been performed utilizing controlled local anesthetic blocks. Pain
      relief was categorized as at least 50% pain relief from baseline pain and the
      ability to perform previously painful movements. RESULTS: A total of 25
      diagnostic accuracy studies were included. Of these, one study evaluated 50% to
      74% relief as criterion standard with a single block with prevalence of 48%, 4
      studies evaluated 75% to 100% relief as the criterion standard with a single
      block with a prevalence of 31% to 61%, 5 studies evaluated 50% to 74% relief as
      the criterion standard with controlled blocks with a prevalence of 15% to 61%,
      and 13 studies evaluated 75% to 100% relief as the criterion standard with
      controlled blocks with a prevalence of 25% to 45% in heterogenous populations.
      False-positive rates ranged from 17% to 66% relief and 27% to 49% with at least
      75% relief as the criterion standard. Based on this evaluation, the evidence
      showed that there is good evidence for diagnostic facet joint nerve blocks with
      75% to 100% pain relief as the criterion standard with dual blocks and fair
      evidence with 50% to 74% pain relief as the criterion standard with controlled
      diagnostic blocks; however, the evidence is poor with single diagnostic blocks of
      50% to 74%, and limited for 75% or more pain relief as the criterion standard.
      LIMITATIONS: The shortcomings of this systematic review of the accuracy of
      diagnostic lumbar facet joint nerve blocks include a paucity of literature and
      continued debate on an appropriate gold standard. CONCLUSION: There is good
      evidence for diagnostic facet joint nerve blocks with 75% to 100% pain relief as
      the criterion standard with dual blocks, with fair evidence with 50% to 74% pain
      relief.

PMID- 23159980
TI  - An update of the effectiveness of therapeutic lumbar facet joint interventions.
AB  - BACKGROUND: Therapeutic lumbar facet joint interventions are implemented to
      provide long-term pain relief after the facet joint has been identified as the
      basis for low back pain. The therapeutic lumbar facet joint interventions
      generally used for the treatment of low back pain of facet joint origin are
      intraarticular facet joint injections, lumbar facet joint nerve blocks, and
      radiofrequency neurotomy. OBJECTIVE: To evaluate and update the effect of
      therapeutic lumbar facet joint interventions in managing chronic low back pain.
      STUDY DESIGN: A systematic review of therapeutic lumbar facet joint interventions
      for the treatment of chronic low back pain. METHODS: The available literature on
      lumbar facet joint interventions in managing chronic low back pain was reviewed.
      The quality assessment and clinical relevance criteria utilized were the Cochrane
      Musculoskeletal Review Group criteria as utilized for interventional techniques
      for randomized trials and the criteria developed by the Newcastle-Ottawa Scale
      criteria for observational studies. The level of evidence was classified as good,
      fair, and limited or poor based on the quality of evidence developed by the U.S.
      Preventative Services Task Force. Data sources included relevant literature
      identified through searches of PubMed and EMBASE from 1966 through June 2012, and
      manual searches of the bibliographies of known primary and review articles.
      OUTCOME MEASURES: The primary outcome measure was pain relief with short-term
      relief defined as up to 6 months and long-term relief as 12 months. Secondary
      outcome measures were improvement in functional status, psychological status,
      return to work, and reduction in opioid intake. RESULTS: For this systematic
      review, 122 studies were identified. Of these, 11 randomized trials and 14
      observational studies met inclusion criteria for methodological quality
      assessment. The evidence for radiofrequency neurotomy is good and fair to good
      for lumbar facet joint nerve blocks for short- and long-term improvement; whereas
      the evidence for intraarticular injections and pulsed radiofrequency neurotomy is
      limited. LIMITATIONS: The limitations of this systematic review include the
      continued paucity of evidence, specifically for intraarticular injection therapy.
      CONCLUSION: In summary, there is good evidence for the use of conventional
      radiofrequency neurotomy, and fair to good evidence for lumbar facet joint nerve
      blocks for the treatment of chronic lumbar facet joint pain resulting in short
      term and long-term pain relief and functional improvement. There is limited
      evidence for intraarticular facet joint injections and pulsed radiofrequency
      thermoneurolysis.

PMID- 23159981
TI  - Assessment of practice patterns of perioperative management of antiplatelet and
      anticoagulant therapy in interventional pain management.
AB  - BACKGROUND: The role of antithrombotic therapy is well known for its primary and
      secondary prevention of cardiovascular disease by decreasing the incidence of
      acute cerebral, cardiovascular, peripheral vascular, and other thrombotic events.
      The overwhelming data show that the risk of thrombotic events is significantly
      higher than that of bleeding during surgery after antiplatelet drug
      discontinuation. It has been assumed that discontinuing antiplatelet therapy
      prior to performing interventional pain management techniques is a common
      practice, even though doing so may potentially increase the risk of acute
      cerebral and cardiovascular events. There are no data available concerning these
      events, specifically in relation to the occurrence of thromboembolic events, even
      though some data are available concerning bleeding complications. Even then,
      interventionalists seem to routinely discontinue all antithrombotic therapy prior
      to all interventional pain management techniques. OBJECTIVE: To assess the
      perioperative antiplatelet and anticoagulant practice patterns of US
      interventional pain management physicians as well as adverse events in patients
      on antithrombotic therapy who undergo interventional pain management techniques
      when that therapy is continued or stopped. STUDY DESIGN: An online survey of
      interventional pain management physicians. STUDY SETTING: Interventional pain
      management practices in the United States. METHODS: An online survey was
      commissioned among 2,300 members of the American Society of Interventional Pain
      Physicians. The survey was designed to assess practice patterns and complications
      encountered. RESULTS: Of the 2,300 members surveyed, 325 responded. These results
      showed that all physicians discontinued warfarin therapy; whereas, 97%
      discontinued clopidogrel; 96% ticlopidine; 95% Aggrastat (tirofiban); 93%
      cilostazol, 85% dipyridamole, 60% aspirin 350 mg; 39% aspirin 81 mg; and 39%
      other nonsteroidal anti-inflammatory drugs (NSAIDs) prior to performing
      interventional pain management techniques. The majority of physicians accepted an
      international normalized ratio of 1.5 or less as a safe level. An assessment of
      serious complications showed thromboembolic events were 3 times more frequent
      than bleeding complications: 162 thromboembolic events and 55 serious bleeding
      complications from epidural hematomas. Thromboembolic complications were severe
      and higher when antiplatelet therapy was discontinued. Bleeding complications
      from epidural hematomas were similar whether antiplatelet therapy was continued
      or discontinued (26 versus 29). LIMITATIONS: This study was limited by its being
      an online survey of the membership of one organization in one country and that
      there was a 14% response rate. Underreporting in surveys is common. Further, the
      incidence of thromboembolic events or epidural hematomas may be misrepresented as
      a percentage since these drugs were continued in a very small percentage of
      patients. Consequently, the incidences described in this manuscript may not show
      appropriate percentages. CONCLUSION: The results illustrate an overwhelming
      pattern of discontinuing antiplatelet and warfarin therapy as well as aspirin and
      other NSAIDs prior to performing interventional pain management techniques.
      However, thromboembolism complications may be 3 times more prevalent than
      epidural hematomas (162 versus 55 events). It is concluded that clinicians must
      balance the risks of thromboembolism and bleeding in each patient prior to the
      routine discontinuation of antiplatelet therapy.

PMID- 23159982
TI  - Utilization of interventional techniques in managing chronic pain in the Medicare
      population: analysis of growth patterns from 2000 to 2011.
AB  - BACKGROUND: Reports from the United States Government Accountability Office
      (GAO), the Institute of Medicine (IOM), the Medicare Payment Advisory Commission
      (MedPAC), and the Office of Inspector General (OIG) continue to express
      significant concern with the overall fiscal sustainability of Medicare and the
      exponential increase in costs for chronic pain management. STUDY DESIGN: The
      study is an analysis of the growth of interventional techniques in managing
      chronic pain in Medicare beneficiaries from 2000 to 2011. OBJECTIVE: To evaluate
      the use of all interventional techniques 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: Interventional techniques for chronic pain have increased dramatically
      from 2000 to 2011. Overall, the increase of interventional pain management (IPM)
      procedures from 2000 to 2011 went up 228%, with 177% per 100,000 Medicare
      beneficiaries. The increases were highest for facet joint interventions and
      sacroiliac joint blocks with a total increase of 386% and 310% per 100,000
      Medicare beneficiaries, followed by 168% and 127% for epidural and adhesiolysis
      procedures, 150% and 111% for other types of nerve blocks and finally, 28% and 8%
      increases for percutaneous disc procedures. The geometric average of annual
      increases was 9.7% overall with 13.7% for facet joint interventions and
      sacroiliac joint blocks and 7.7% for epidural and adhesiolysis procedures.
      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. CONCLUSION: Interventional techniques
      increased significantly in Medicare beneficiaries from 2000 to 2011. Overall,
      there was an increase of 177% in the utilization of IPM services per 100,000
      Medicare beneficiaries, with an annual geometric average increase of 9.7%. The
      study also showed an exponential increase in facet joint interventions and
      sacroiliac joint blocks.

PMID- 23159983
TI  - Survey of European pain medicine practice.
AB  - This survey was undertaken to explore the variation in the functional
      constitution of pain clinics in Europe. In addition, we also explored the amount
      of training which doctors practicing pain medicine typically receive. Approximate
      hospital charges for common pain interventions and the source of funding were
      also surveyed. Members of the British Pain Society (Interventional Pain Medicine
      Special Interest Group) and other pain physicians in Europe responded through the
      online questionnaire tool "Survey Monkey." About 215 requests were sent; 82 pain
      practitioners from 13 countries in Europe responded. This survey indicates that
      chronic pain interventions are primarily funded either through government or
      insurance companies. The primary chronic pain service members continue to be
      anesthesiologists, combined with specialist nurses and physiotherapists. There
      appears to be some consistency, both with regard to working in a
      multidisciplinary team, and the training required to become a pain specialist.
      More than half of the respondents reported the cost of common interventions like
      caudal epidural steroid injection (ESI), transforaminal ESI, 3 level medial
      branch blocks, and 6 level facet joint injections to fall under the ?500 range
      ($645). Two thirds of the respondents reported the cost of 4-joint radiofrequency
      lumbar denervation to be less than ?1,500 ($1,935). Good practice should ensure
      an adequate duration of training, and development of a pain faculty to ensure
      standards of assessments across the continent. A more detailed, large scale
      survey is perhaps required to map the availability of chronic pain services and
      understand the health economics in pain medicine across Europe.

PMID- 23159984
TI  - Triptolide prevents and attenuates neuropathic pain via inhibiting central immune
      response.
AB  - BACKGROUND: Current treatments for neuropathic pain are far from satisfactory.
      Considering the essential contribution of central immune factors to the
      pathogenesis of neuropathic pain, targeting inflammatory response is well
      accepted as an effective strategy for treating neuropathic pain. Triptolide has a
      long history in traditional Chinese medicine for treating inflammatory diseases
      and has been proven to inhibit cytokines released from glial cells. OBJECTIVE: In
      the present study, we tested whether systemic treatment with triptolide could
      prevent or attenuate nocifensive behaviors associated with neuropathic pain. We
      further tried to explore the underlying mechanism of the potential anti-allodynia
      effect of triptolide. STUDY DESIGN: A randomized, double blind, controlled animal
      trial. METHODS: Triptolide was administered systemically in a rat model of
      neuropathic pain induced by spinal nerve ligation (SNL) in the single bolus and
      repeated treatment manners. In the single bolus treatment experiment, triptolide
      (30 ug/kg, 100 ug/kg, 300 ug/kg) or vehicle was given to SNL and sham-operated
      rats once on day 1 or on day 10 after surgery (n = 6 each). In the repeated
      treatment study, prophylactic treatment with triptolide (30 ug/kg, 100 ug/kg, 300
      ug/kg) was given to rats during the period of day -3 (3 days prior to SNL) to day
      7 (7 days post-SNL) inclusively (n = 6 each). Another set of SNL and sham rats on
      postoperative day 10 received treatment with triptolide (30 ug/kg, 100 ug/kg, 300
      ug/kg) or vehicle during the period of days 11-20 inclusively (n = 6 each), to
      assess potential reversal of established pain behavior. Mechanical allodynia of
      the rats was tested with von Frey filaments. Astrocytic and microglial activation
      in the spinal dorsal horn was evaluated with immunofluorescent histochemistry.
      Phosphorylation of mitogen-activated protein kinases (MAPKs), and expression of
      inflammatory cytokines (interleukin-6, interleukin-1beta, monocyte chemotactic
      protein-1, and tumor necrosis factor-alpha) were examined with Western blot
      analysis and real-time reverse transcription polymerase chain reaction study.
      RESULTS: A single bolus treatment with triptolide could neither prevent the
      induction nor reverse the maintenance of SNL-induced mechanical allodynia.
      However, repeated administration of triptolide dose-dependently inhibited
      neuropathic pain behavior in both preventative and interventional paradigms.
      Triptolide hampered SNL-induced activation of glial cells (astrocytes and
      microglia) in the spinal dorsal horn without influencing neurons. In addition,
      SNL-induced phosphorylation of MAPKs could be inhibited by triptolide.
      Furthermore, up-regulated expression of inflammatory cytokines in neuropathic
      pain states could be remarkably blocked by triptolide. LIMITATIONS: The direct
      target site (such as a specific receptor) of triptolide is still to be
      determined. In addition, triptolide could not completely block the SNL-induced
      mechanical allodynia. CONCLUSIONS: Our data suggest that triptolide may be a
      potential novel treatment for neuropathic pain through modulating immune response
      in the spinal dorsal horn.

PMID- 23159985
TI  - Analysis of microRNA and gene expression profiling in triazole fungicide-treated
      HepG2 cell line.
AB  - MicroRNA (miRNA) plays an important role in various diseases and in cellular and
      molecular responses to toxicants. In the present study, we investigated
      differential expression of miRNAs in response to three triazole fungicides
      (myclobutanil, propiconazole, and triadimefon). The human hepatoma cell line
      (HepG2) was treated with the above triazoles for 3 h or 48 h. miRNA-based
      microarray experiments were carried out using the Agilent human miRNA v13 array.
      At early exposure (3h), six miRNAs were differentially expressed and at late
      exposure (48 h), three miRNAs were significantly expressed. Overall, this study
      provides an array of potential biomarkers for the above triazole fungicides.
      Furthermore, these miRNAs induced by triazoles could be the foundation for the
      development of a miRNA-based toxic biomarker library that can predict
      environmental toxicity.

PMID- 23159986
TI  - Renal biomarker changes associated with hyaline droplet nephropathy in rats are
      time and potentially compound dependent.
AB  - Alpha 2u-globulin mediated hyaline droplet nephropathy (HDN) is a male rat
      specific lesion induced when a compound or metabolite binds to alpha 2u-globulin.
      The objective of this study was to investigate if the newer and more sensitive
      renal biomarkers would be altered with HDN as well as be able to distinguish
      between HDN and oxidative stress-induced kidney injury. Rats were dosed orally
      for 7 days to determine (1) if HDN (induced by 2-propanol or D-limonene) altered
      the newer renal biomarkers and not BUN or creatinine, (2) if renal biomarkers
      could distinguish between HDN and oxidative stress-induced kidney injury (induced
      by potassium bromate), (3) sensitivity of HDN-induced renal biomarker changes
      relative to D-limonene dose, and (4) reversibility of HDN and renal biomarkers,
      using vehicle or 300 mg/kg/day D-limonene with 7 days of dosing and necropsies
      scheduled over the period of Days 8-85. HDN-induced renal biomarker changes in
      male rats were potentially compound specific: (1) 2-propanol induced mild HDN
      without increased renal biomarkers, (2) potassium bromate induced moderate HDN
      with increased clusterin, and (3) D-limonene induced marked HDN with increased
      alphaGST, MUGST and albumin. Administration of potassium bromate did not result
      in oxidative stress-induced kidney injury, based on histopathology and renal
      biomarkers creatinine and BUN. The compound D-limonene induced a dose dependent
      increase in HDN severity and renal biomarker changes without altering BUN,
      creatinine or NAG: (1) minimal induction of HDN and no altered biomarkers at 10
      mg/kg/day, (2) mild induction of HDN with increased alphaGST and MUGST at 50
      mg/kg/day and (3) marked induction of HDN with increased alphaGST, MUGST and
      albumin at 300 mg/kg/day. HDN induced by D-limonene was reversible, but with a
      variable renal biomarker pattern over time: Day 8 there was increased alphaGST,
      MUGST and albumin; on Day 15 increased clusterin, albumin and Kim-1. In summary,
      HDN altered the newer and more sensitive renal biomarkers in a time and possibly
      compound dependent manner.

PMID- 23159987
TI  - Expression and function of OXE receptor, an eicosanoid receptor, in steroidogenic
      cells.
AB  - Hormonal regulation of steroidogenesis involves arachidonic acid (AA) metabolism
      through the 5-lipoxygenase pathway. One of the products, 5-hydroperoxy
      eicosatetraenoic acid (5-HpETE), acts as a modulator of the activity of the
      steroidogenic acute regulatory (StAR) protein promoter. Besides, an oxoeicosanoid
      receptor of the leukotriene receptor family named OXE-R is a membrane protein
      with high affinity and response to 5-HpETE, among other AA derivatives. The aim
      of our work was to elucidate whether this receptor may be involved in
      steroidogenesis. RT-PCR and western blot analysis demonstrated the presence of
      the mRNA and protein of the receptor in human H295R adrenocortical cells. The
      treatment of H295R or MA-10 cells (murine Leydig cell line) with 8Br-cAMP
      together with docosahexaenoic acid (DHA, an antagonist of the receptor) partially
      reduced StAR induction and steroidogenesis. On the contrary, 5-oxo-ETE - the
      prototypical agonist, with higher affinity and potency on the receptor -
      increased cAMP-dependent steroid production, StAR mRNA and protein levels. These
      results lead us to conclude that AA might modulate StAR induction and
      steroidogenesis, at least in part, through 5-HpETE production and activation of a
      membrane receptor, such as the OXE-R.

PMID- 23159988
TI  - Nuclear receptors, bile acids and cholesterol homeostasis series - bile acids and
      pregnancy.
AB  - Bile acids have been traditionally thought of as having an important role in fat
      emulsification. It is now emerging that they act as important signalling
      molecules that not only autoregulate their own synthesis but also influence lipid
      and glucose metabolism. Although, the mechanisms that underlie the regulation of
      bile acid homeostasis have been well characterised in normal physiology, the
      impact of pregnancy on bile acid regulation is still poorly understood. This
      review summarises the main regulatory mechanisms underlying bile acid homeostasis
      and discusses how pregnancy, a unique physiological state, can modify them. The
      fetoplacental adaptations that protect against fetal bile acid toxicity are
      reviewed. We highlight the importance of bile acid regulation during gestation by
      discussing the liver disease of pregnancy, intrahepatic cholestasis of pregnancy
      (ICP) and how genetic, endocrine and environmental factors contribute to the
      disease aetiology at a cellular and molecular level.

PMID- 23159989
TI  - Expression and regulation of beta-defensin 11 in the oviduct in response to
      estrogen and in ovarian tumors of chickens.
AB  - Avian beta-defensins (AvBDs), also known as gallinacins, are small cationic
      peptides having three cysteine disulfide bonds between their cysteine residues.
      They play essential roles in the innate immune system as well as stimulate
      proliferation of epithelial cells and fibroblasts. Although we found the avian
      homolog of human beta-defensin 11 to be highly expressed in chicks treated with
      the diethylstilbestrol (DES, a synthetic estrogen agonist), little is known about
      the hormonal and transcriptional regulation of AvBD-11 in the chicken oviduct and
      its expression in cancerous ovaries of chickens. Results of this study of young
      chicks revealed that DES induced AvBD-11 mRNA and protein in the oviduct,
      specifically luminal and glandular epithelial cells. In addition, microRNA-1615
      was discovered to influence AvBD-11 expression via its 3'-UTR which suggests post
      transcriptional regulation of AvBD-11 expression in chickens. Furthermore, we
      compared the expression patterns of the AvBD-11 gene in normal and cancerous
      ovaries from laying hens which are models for human epithelial ovarian cancer.
      Our results demonstrated that AvBD-11 is most abundant in the glandular
      epithelium of endometrioid-type ovarian tumors, but not normal ovaries of laying
      hens. Collectively, these results suggest that AvBD-11 is an estrogen-induced
      gene during oviduct development and that it may be used as a biomarker for
      diagnosis of ovarian cancer and for monitoring effects of therapeutics on
      progression of ovarian carcinogenesis.

PMID- 23159990
TI  - Does benign prostatic hyperplasia treatment with alpha-blockers affect prostate
      cancer risk?
AB  - PURPOSE OF REVIEW: To determine whether alpha-blockers, commonly used for the
      treatment of benign prostatic hyperplasia, are associated with prostate cancer
      risk. RECENT FINDINGS: Alpha-blockers have been associated with a reduced risk of
      prostate cancer aggressiveness in some observational studies and an increased
      risk in other studies. However, this relationship is complex as different alpha
      blockers have divergent effects in laboratory studies and there are many
      confounders in daily practice such as differential screening practices. SUMMARY:
      Both benign prostatic hyperplasia and prostate cancer are common conditions in
      the aging male population, such that an interaction between alpha-blockers and
      prostate cancer risk is clinically relevant. Prospective evidence is necessary to
      establish a definitive link.

PMID- 23159991
TI  - Correlation between benign prostatic hyperplasia and inflammation.
AB  - PURPOSE OF REVIEW: This review aims to evaluate the available evidence on the
      role of prostatic inflammation in the pathogenesis and progression of benign
      prostatic hyperplasia (BPH). RECENT FINDINGS: Although there is still no evidence
      of a causal relation, accumulating evidence suggests that inflammation may
      contribute to the development of BPH and lower urinary tract symptoms (LUTS).
      Inflammatory infiltrates are frequently observed in prostate tissue specimens
      from men with BPH and the presence or degree of inflammation has been found to be
      correlated with prostate volume and weight. The inflammatory injury may
      contribute to cytokine production by inflammatory cells driving local growth
      factor production and angiogenesis in the prostatic tissue. This proinflammatory
      microenvironment is closely related to BPH stromal hyperproliferation and tissue
      remodeling with a local hypoxia induced by increased oxygen demands by
      proliferating cells which supports chronic inflammation as a source of oxidative
      stress leading to tissue injury in infiltrating area. SUMMARY: Although the
      pathogenesis of BPH is not yet fully understood and several mechanisms seem to be
      involved in the development and progression, recent studies strongly suggest that
      BPH is an immune inflammatory disease. The T-cell activity and associated
      autoimmune reaction seem to induce epithelial and stromal cell proliferation.
      Further understanding of the role of inflammation in BPH and clinical detection
      of this inflammation will expand the understanding of BPH pathogenesis and its
      histologic and clinical progression, allow risk stratification for patients
      presenting with BPH-related LUTS, and suggest novel treatment strategies.

PMID- 23159992
TI  - Robotic retroperitoneal surgery:  a contemporary review.
AB  - PURPOSE OF REVIEW: Robotic-assisted renal surgery is being increasingly utilized
      for various kidney diseases; however, the majority of these are performed via a
      transperitoneal approach. Retroperitoneal robotic surgery is a relatively new
      technique, which allows direct access to the posterolateral surface of the
      kidney, as well as posterior hilar structures. In this review, we summarize the
      most recent publications and review our experience of retroperitoneal robotic
      surgery. RECENT FINDINGS: Retroperitoneal robotic surgery has been successfully
      applied to radical nephrectomy, partial nephrectomy and pyeloplasty. The current
      series, although few, find this approach ideal for posterior and lateral renal
      masses, and technically feasible with the advances in robotic technology. The
      retroperitoneal approach has been shown to decrease operative times, narcotic
      need and permit quicker return of bowel function. Furthermore, there does not
      appear to be any increase in perioperative complications using this approach.
      SUMMARY: The limited data using this technique offer an encouraging outlook on
      robotic retroperitoneal surgery. The retroperitoneal approach permits direct
      access to the renal hilum, no need for bowel mobilization and excellent
      visualization for posteriorly located renal disease.

PMID- 23159993
TI  - Development of STEADI: a fall prevention resource for health care providers.
AB  - Falls among people aged >=65 years are the leading cause of both injury deaths
      and emergency department visits for trauma. Research shows that many falls are
      preventable. In the clinical setting, an effective fall intervention involves
      assessing and addressing an individual's fall risk factors. This individualized
      approach is recommended in the American and British Geriatrics Societies'
      (AGS/BGS) practice guideline. This article describes the development of STEADI
      (Stopping Elderly Accidents, Deaths, and Injuries), a fall prevention tool kit
      that contains an array of health care provider resources for assessing and
      addressing fall risk in clinical settings. As researchers at the Centers for
      Disease Control and Prevention's Injury Center, we reviewed relevant literature
      and conducted in-depth interviews with health care providers to determine current
      knowledge and practices related to older adult fall prevention. We developed
      draft resources based on the AGS/BGS guideline, incorporated provider input, and
      addressed identified knowledge and practice gaps. Draft resources were reviewed
      by six focus groups of health care providers and revised. The completed STEADI
      tool kit, Preventing Falls in Older Patients-A Provider Tool Kit, is designed to
      help health care providers incorporate fall risk assessment and individualized
      fall interventions into routine clinical practice and to link clinical care with
      community-based fall prevention programs. 

PMID- 23159994
TI  - Conceptualizing, implementing, and monitoring a structural health promotion
      intervention in an organizational setting.
AB  - This article presents a framework for developing and carrying out an
      implementation monitoring plan of a complex structural intervention in an
      organizational setting and describes seven steps for analyzing and reporting
      results for fidelity and completeness of implementation. This process is
      illustrated using the Environmental Interventions in Children's Homes (ENRICH)
      Wellness Project. ENRICH aimed to promote physical activity and healthful
      nutrition behaviors among children residing in children's group homes by working
      collaboratively with organizational staff. A comprehensive implementation
      monitoring plan was developed based on the particulars of the setting, context,
      and the program framework and used multiple data sources, criteria for evidence
      of implementation, and data triangulation to examine evidence for organizational
      implementation. Eleven of 17 organizations (65%) met the criteria for nutrition
      implementation whereas 9 of 17 (53%) met the criteria for physical activity
      implementation. Implementation data can be used descriptively, as described here,
      and may also be used in future outcome analyses to better understand project
      outcomes. The framework and evaluation approach are applicable to complex
      interventions in other organizational settings.

PMID- 23159995
TI  - A content analysis of nutrition education curricula used with low-income
      audiences: implications for questionnaire development.
AB  - In developing recommendations for core measures/items for the evaluation of the
      Youth Expanded Food and Nutrition Education Program (EFNEP), three nutrition
      education curricula, implemented by land grant universities, were content
      analyzed. Selection criteria included the following: Curriculum content must
      include all EFNEP core content areas and must be implemented in more than one
      state with school children in third through fifth grades. Content analysis
      strategies were employed to identify and describe common areas/themes and
      mediators of behaviors addressed across the selected curricula. Content analysis
      coding was based on a list of behavioral mediators, which have empirical
      associations with nutrition, physical activity, and food safety. The most evident
      approaches identified across the three curricula were to enhance motivation,
      teach cognitive knowledge, and practice behavioral skills. The presence of self
      regulation and environmental theory-based strategies was limited in all three
      curricula. In addition, multiple themes for nutrition, physical activity, and
      food safety were commonly addressed across curricula with multiple educational
      strategies. Based on these findings, recommendations for developing content
      appropriate measures and items for an outcome evaluation tool for Youth EFNEP are
      provided.

PMID- 23159996
TI  - Linking physical education with community sport and recreation: a program for
      adolescent girls.
AB  - The engagement of adolescent girls in physical activity (PA) is a persistent
      challenge. School-based PA programs have often met with little success because of
      the lack of linkages between school and community PA settings. The Triple G
      program aimed to improve PA levels of secondary school girls (12-15 years) in
      regional Victoria, Australia. The program included a school-based physical
      education (PE) component that uniquely incorporated student-centered teaching and
      behavioral skill development. The school component was conceptually and
      practically linked to a community component that emphasized appropriate
      structures for participation. The program was informed by ethnographic fieldwork
      to understand the contextual factors that affect girls' participation in PA. A
      collaborative intervention design was undertaken to align with PE curriculum and
      coaching and instructional approaches in community PA settings. The theoretical
      framework for the intervention was the socioecological model that was underpinned
      by both individual-level (social cognitive theory) and organizational-level
      (building organizational/community capacity) strategies. The program model
      provides an innovative conceptual framework for linking school PE with community
      sport and recreation and may benefit other PA programs seeking to engage
      adolescent girls. The objective of this article is to describe program
      development and the unique theoretical framework and curriculum approaches. 

PMID- 23159997
TI  - Australian blue-collar men's health and well-being: contextual issues for
      workplace health promotion interventions.
AB  - In Australia, blue-collar workers are predominantly male and form a unique and
      large (approximately 30%) subset of the Australian workforce. They exhibit
      particular health-related issues and, in comparison to other groups, often a lack
      of health promoting behavior. This article briefly discusses the Australian
      context and some of the key health issues blue-collar men face, in particular as
      it relates to construction workers. It reviews the impact of gender and
      socioeconomic factors in designing workplace health promotion interventions. This
      article considers practice strategies for health promoters in a specific
      workplace setting: it looks at meta-factors and industry-based contextual
      factors, including barriers to implementation and participation, while addressing
      common misconceptions about Australian blue-collar workers. 

PMID- 23159998
TI  - How can both the intervention and its evaluation fulfill health promotion
      principles? An example from a professional development program.
AB  - The emergence over the past 20 years of health promotion discourse poses a
      specific challenge to public health professionals, who must come to terms with
      new roles and new intervention strategies. Professional development is, among
      other things, a lever for action to be emphasized in order to meet these
      challenges. To respond to the specific training needs of public health
      professionals, a team from the Direction de sante publique de Montreal (Montreal
      Public Health Department) in Quebec, Canada, established in 2009 the Health
      Promotion Laboratory, an innovative professional development project. An
      evaluative component, which supports the project's implementation by providing
      feedback, is also integrated into the project. This article seeks to demonstrate
      that it is possible to integrate the basic principles of health promotion into a
      professional development program and its evaluation. To this end, it presents an
      analytical reading of both the intervention and its evaluation component in light
      of the cardinal principles in this field. Initiatives such as the Health
      Promotion Laboratory and its evaluation are essential to consolidate the
      foundations of professional development and its assessment by concretely
      integrating health promotion discourse into these practices.

PMID- 23159999
TI  - Using photovoice as a participatory evaluation tool in Kaiser Permanente's
      Community Health Initiative.
AB  - Photovoice is a community-based participatory research method that provides
      participants who traditionally have little voice in community policy decisions,
      with training in photography, ethics, critical dialogue, photo captioning, and
      policy advocacy. Photovoice has been used primarily as a needs assessment and
      advocacy tool and only rarely as a pre-/postintervention evaluation method. This
      article describes the use of Photovoice as a participatory evaluation method in
      the Community Health Initiative, a 6-year, multisite community-based obesity
      prevention initiative, sponsored by Kaiser Permanente. Fifty community
      participants (including six youth) from six Community Health Initiative
      communities used photos and captions to identify, from their perspective, the
      most significant accomplishments from the initiative at both baseline and follow
      up. Accomplishments identified included increased access to fresh/healthy food in
      local neighborhoods; policy changes supporting a "healthy eating, active living"
      community; increased access to physical activity; changes to the built
      environment creating increased neighborhood walkability/safety; and leadership
      development. 

PMID- 23160000
TI  - Costs of management of patients with coronary artery disease in Poland: the
      multicenter RECENT study.
AB  - INTRODUCTION: Treatment of coronary artery disease (CAD) generates the major part
      of public health expenditure in the developed countries. OBJECTIVES: The aim of
      the study was to estimate costs associated with the diagnosis and treatment of
      patients with CAD in Poland. PATIENTS AND METHODS: Costs were estimated in a
      representative sample of 2593 patients with CAD receiving general practitioner (n
      = 1977) or specialist care (n = 616) in 2005 (the multicenter RECENT study). Data
      from the National Health Fund, Social Insurance Institution, Central Statistical
      Office, and current literature were used. RESULTS: The total annual cost of CAD
      reached ?2254.17 per patient, with 48% accounting for direct medical costs
      (drugs, medical consultations, laboratory tests, diagnostic procedures, invasive
      treatment, hospitalizations, emergency care) and 52% for indirect costs (related
      to absence at work and disability). Eighty-one percent of total direct medical
      costs were covered by the public payer (including 30% of pharmacological
      treatment costs). Direct medical costs covered by the public payer were higher in
      men and in patients with more severe angina symptoms (both P <0.05). In the model
      based on the lowest prevalence of CAD (estimated based on the real population of
      patients treated in 2005), direct medical costs covered by the public payer
      reached ?617.6 million, i.e., around 7% of the total public health expenditure in
      Poland in 2005. CONCLUSIONS: Modern management of CAD imposes enormous economic
      burden on the public health system in Poland. There is a need to develop and
      implement strategies that would optimize health care costs associated with the
      treatment of CAD.

PMID- 23160001
TI  - Steroid hormone levels in calling males and males practicing alternative non
      calling mating tactics in the green treefrog, Hyla cinerea.
AB  - Circulating glucocorticoids and androgens often figure prominently in mating
      tactic expression in vertebrates. In anuran amphibians (frogs and toads), for
      example, recent models predict that the depletion of energy reserves during
      vocalization will result in increased glucocorticoid levels; high glucocorticoids
      are expected to negatively affect androgen level to mediate transitions from
      calling to non-calling behavior. Consistent with these predictions, we show that
      male green treefrogs (Hyla cinerea) adopting an alternative non-calling
      "satellite" mating tactic were in poorer condition and had higher circulating
      corticosterone levels and lower androgen levels than calling males. Body
      condition was inversely related to corticosterone level and positively related to
      testosterone, but not dihydrotestosterone, level. Corticosterone level was
      inversely related to testosterone level but not dihydrotestosterone level.
      Lastly, we show that calling males that were involved in aggressive bouts had
      higher corticosterone levels than calling males that were not involved in
      aggressive bouts. Our results are thus consistent with the prediction that
      aggressive interactions with conspecific males contribute to high corticosterone
      levels in satellite males that were observed to lose aggressive contests with
      larger calling males.

PMID- 23160002
TI  - Peptidomic discovery of short open reading frame-encoded peptides in human cells.
AB  - The complete extent to which the human genome is translated into polypeptides is
      of fundamental importance. We report a peptidomic strategy to detect short open
      reading frame (sORF)-encoded polypeptides (SEPs) in human cells. We identify 90
      SEPs, 86 of which are previously uncharacterized, which is the largest number of
      human SEPs ever reported. SEP abundances range from 10-1,000 molecules per cell,
      identical to abundances of known proteins. SEPs arise from sORFs in noncoding
      RNAs as well as multicistronic mRNAs, and many SEPs initiate with non-AUG start
      codons, indicating that noncanonical translation may be more widespread in
      mammals than previously thought. In addition, coding sORFs are present in a small
      fraction (8 out of 1,866) of long intergenic noncoding RNAs. Together, these
      results provide strong evidence that the human proteome is more complex than
      previously appreciated.

PMID- 23160003
TI  - Biomimetic diversity-oriented synthesis of benzannulated medium rings via ring
      expansion.
AB  - Nature has exploited medium-sized 8- to 11-membered rings in a variety of natural
      products to address diverse and challenging biological targets. However, owing to
      the limitations of conventional cyclization-based approaches to medium-ring
      synthesis, these structures remain severely underrepresented in current probe and
      drug discovery efforts. To address this problem, we have established an
      alternative, biomimetic ring expansion approach to the diversity-oriented
      synthesis of medium-ring libraries. Oxidative dearomatization of bicyclic phenols
      affords polycyclic cyclohexadienones that undergo efficient ring expansion to
      form benzannulated medium-ring scaffolds found in natural products. The ring
      expansion reaction can be induced using three complementary reagents that avoid
      competing dienone-phenol rearrangements and is driven by rearomatization of a
      phenol ring adjacent to the scissile bond. Cheminformatic analysis of the
      resulting first-generation library confirms that these molecules occupy chemical
      space overlapping with medium-ring natural products and distinct from that of
      synthetic drugs and drug-like libraries.

PMID- 23160004
TI  - Notch1-mediated signaling regulates proliferation of porcine satellite cells
      (PSCs).
AB  - Notch signaling is an evolutionarily conserved cell-cell communication mechanism
      involved in the regulation of cell proliferation, differentiation and fate
      decisions of mammalian cells. In the present study, we investigated the possible
      requirement for Notch signaling in the proliferation and differentiation of
      porcine satellite cells. We show that Notch1, 2 and 3 are expressed in cultured
      porcine satellite cells. Knock-down of NOTCH1, but not NOTCH2 and NOTCH3,
      decreases the proliferation of porcine satellite cells. In contrast, enhancement
      of NOTCH1 expression via treatment of porcine satellite cells with recombinant NF
      kappaB increases the proliferation of porcine satellite cells. The alteration of
      porcine satellite cell proliferation is associated with significant changes in
      the expression of cell cycle related genes (cyclin B1, D1, D2, E1 and p21),
      myogenic regulatory factors (MyoD and myogenin) and the Notch effector Hes5. In
      addition, alteration of Notch1 expression in porcine satellite cells causes
      changes in the expression of GSK3beta-3. Taken together, these findings suggest
      that of the four notch-related genes, Notch1is likely to be required for
      regulating the proliferation and therefore the maintenance of porcine satellite
      cells in vivo, and do so through activation of the Notch effector gene Hes5.

PMID- 23160005
TI  - Role of the mycobiome in human acute graft-versus-host disease.
AB  - A role for gut bacteria in the pathogenesis of graft-versus-host disease (GVHD)
      has been firmly established; however, the role of Candida spp, which form part of
      the mycobiome, remains unknown. In a homogenous group of patients who underwent
      allogeneic stem cell transplantation (SCT), we found a significant impact of
      Candida colonization on the occurrence of acute GVHD. Patients colonized with
      Candida spp developed significantly more grade II-IV acute GVHD compared with
      noncolonized patients (50% vs 32%; P = .03), as well as more gastrointestinal
      (GI)-GVHD (33% vs 19%; P = .05). Colonization with Candida spp was more frequent
      in patients bearing the loss-of-function polymorphism Y238X, which results in
      dectin-1 dysfunction, compared with patients with the wild-type allele (73% vs
      31%; P = .002). There was no direct effect of dectin-1 dysfunction on acute GVHD,
      although it did influence the occurrence of GVHD indirectly through Candida
      colonization. The exact mechanism of GVHD induction by Candida spp colonization
      of the mucosa is unknown, but the link might prove to be the induction of Th
      17/IL-23 responses through activation of pattern recognition receptors by fungal
      motifs, including beta-d-glucan and mannans. These data indicate a role for the
      mycobiome in the pathogenesis of GVHD and suggest that altering the mycobiome by
      antifungal drugs can help ameliorate GI-GVHD. In addition, given that the genetic
      constitution of patients affects susceptibility to both Candida colonization and
      GVHD, whether identifying gene polymorphisms will facilitate personalized
      treatment of SCT recipients remains to be determined.

PMID- 23160006
TI  - Pilot study of comprehensive geriatric assessment (CGA) in allogeneic transplant:
      CGA captures a high prevalence of vulnerabilities in older transplant recipients.
AB  - Comprehensive geriatric assessment (CGA) is frequently used in oncology to
      measure the health status of older adults with cancer, but it has not been
      studied in allogeneic hematopoietic cell transplantation (HCT). We conducted a
      prospective pilot study of CGA in allogeneic HCT recipients aged >=50 years to
      examine the prevalence of vulnerabilities in this population. Patients aged >=50
      years eligible for HCT were enrolled. CGA consisted mainly of self-reported,
      performance-based, and chart-extracted measures evaluating domains of
      comorbidity, physical and mental function, frailty, disability, and nutrition. Of
      238 eligible patients, 166 completed CGA and underwent HCT. Only 1% had a Zubrod
      Performance Status score >1; 44% had high comorbidity defined by the
      Hematopoietic Cell Transplantation Comorbidity Index, and 66% had high
      comorbidity defined by the Cumulative Illness Rating Scale-Geriatrics. The
      presence of additional vulnerability was frequent. Disability was present in 40%
      by Instrumental Activities of Daily Living. Self-reported physical and mental
      function were significantly lower than population age group norms, 58% were pre
      frail, and 25% were frail. Among those with Zubrod Performance Status score of 0,
      28% demonstrated disability, 58% were pre-frail, 15% were frail, 35% reported low
      physical function, and 55% reported low mental function. CGA uncovers a
      substantial prevalence of undocumented impairments in functional status, frailty,
      disability, and mental health in older allogeneic HCT recipients.

PMID- 23160007
TI  - Treosulfan-thiotepa-fludarabine-based conditioning regimen for allogeneic
      transplantation in patients with thalassemia major: a single-center experience
      from north India.
AB  - Hematopoietic stem cell transplantation (HSCT) is the definite treatment for
      patients with thalassemia major. A busulfan (Bu) and cyclophosphamide (Cy)-based
      regimen has been the standard myeloablative chemotherapy, but it is associated
      with higher treatment-related toxicity, particularly in patients classified as
      high risk by the Pesaro criteria. Treosulfan-based conditioning regimens have
      been found to be equally effective and less toxic. Consequently, we analyzed the
      safety and efficacy of treosulfan/thiotepa/fludarabine (treo/thio/flu)-based
      conditioning regimens for allogeneic HSCT in patients with thalassemia major
      between February 2010 and September 2012. We compared those results
      retrospectively with results in patients who underwent previous HSCT with a
      Bu/Cy/antithymocyte globulin (ATG)-based conditioning regimen. A treo/thio/flu
      based conditioning regimen was used in 28 consecutive patients with thalassemia
      major. The median patient age was 9.7 years (range, 2-18 years), and the mean
      CD34(+) stem cell dose was 6.18 * 10(6)/kg. Neutrophil and platelet engraftment
      occurred at a median of 15 days (range, 12-23 days) and 21 days (range, 14-34
      days), respectively. Three patients developed veno-occlusive disease, 4 patients
      developed acute graft-versus-host disease (GVHD), and 2 patients had chronic
      GVHD. Treatment-related mortality (TRM) was 21.4%. Two patients experienced
      secondary graft rejection. We compared these results with results in patients who
      underwent previous HSCT using a Bu/Cy/ATG-based conditioning regimen. Twelve
      patients were treated with this protocol, at a median age of 7.2 years (range, 2
      11 years). One patient had moderate veno-occlusive disease, 2 patients developed
      acute GVHD, 2 patients had chronic GVHD, and 2 patients experienced graft
      rejection. There was no TRM in this group. We found no significant differences
      between the 2 groups (treo/thio/flu vs Bu/Cy/ATG) in terms of the incidence of
      acute GVHD, chronic GVHD, TRM, and graft failure, although a trend toward higher
      TRM was seen with the treo/thio/flu regimen.

PMID- 23160008
TI  - Prevention of amyloid-beta fibril formation using antibodies against the C
      terminal region of amyloid-beta1-40 and amyloid-beta1-42.
AB  - Alzheimer's disease is characterized by the abnormal aggregation of amyloid-beta
      (Abeta)1-40 and Abeta1-42 peptides into fibrils. In this work, we analyzed the
      kinetics of Abeta1-40 and Abeta1-42 fibril formation in vitro using Thioflavin T
      fluorescence. We synthesized high-purity peptides and performed a hexafluoro-2
      propanol pre-treatment to yield uniform peptide solutions as starting materials.
      We found that the aggregation is clearly affected by the presence of sub
      millimolar quantities of antibodies against the C-terminal region of the
      peptides. Because the fibrillization of these peptides is closely related to the
      pathogenesis of Alzheimer's disease, blocking this process may provide
      significant therapeutic benefit.

PMID- 23160009
TI  - The 2008-2012 French Alzheimer plan: a unique opportunity for improving
      integrated care for dementia.
AB  - The 2008-2012 French Alzheimer plan has proposed measures to improve care for
      dementia patients in a more personalized and graduate approach owing to patients
      and caregivers needs. A key measure of the plan is the nationwide implementation
      of the MAIA (French acronym for Maison pour l'Autonomie et l'Integration des
      malades d'Alzheimer). The main goal is to implement a process of integration
      through a network of partners involved in elderly care, assistance, or support.
      The MAIA model comprises tools and mechanisms necessary to improve the integrated
      care process; in particular, case management for elderly in complex situations.
      The purpose of this paper is to describe the main measures from the national plan
      that aim to improve care for dementia patients with an emphasis on the MAIA
      measure. We summarize initial results of case management activity in one MAIA in
      the South West of France and we present two vignettes of cases benefiting from
      case management in order to demonstrate the nature of intervention. The French
      Alzheimer plan has promoted several non-pharmacological strategies for dementia
      patients. Implementation of both integrated care and case management represent a
      challenging perspective for the elderly and health professionals.

PMID- 23160010
TI  - Studies on the mechanism of the DNA nicking property of amyloid-beta40:
      implications in Alzheimer's disease.
AB  - Amyloid-beta peptide is presumably a key etiological factor involved in the
      pathogenesis of Alzheimer's disease (AD), and several hypotheses exist on the
      possible ways Abeta contributes to the progression of the disease. There are
      reports on the nuclear localization of Abeta and very limited evidence on its DNA
      binding property. The present study provided the mechanism of Abeta enantiomers
      binding to DNA and showed that Abeta40L induces psi-DNA, while Abeta40D causes
      only altered B-DNA. Further, we evidenced the DNA nicking property of Abeta
      enantiomers and endonuclease mimicking behavior. The role of Abeta in modulating
      DNA stability was reported by altered melting temperature and ethidium bromide
      binding studies. The data provides new evidence on stereospecific dependent Abeta
      DNA interaction and we discuss its biological relevance to neurodegeneration. Our
      results imply that Abeta-DNA interaction needs to be considered as a significant
      cause of the toxicity in the pathogenesis of AD.

PMID- 23160011
TI  - Cognitive decline in adults with amnestic mild cognitive impairment and high
      amyloid-beta: prodromal Alzheimer's disease?
AB  - We aimed to characterize the nature and magnitude of cognitive decline in a group
      of adults with amnestic mild cognitive impairment (aMCI) with high and low levels
      of amyloid-beta (Abeta) in relation to healthy older adults with low Abeta
      levels. Healthy older adults and adults with aMCI enrolled in the Australian
      Imaging, Biomarker, and Lifestyle study, completed the CogState brief battery at
      baseline and 18 months, and underwent positron emission tomography neuroimaging
      for Abeta at baseline. In this study, we included adults with MCI who had been
      classified as having high and low levels of Abeta and healthy older adults who
      had been classified as having low levels of Abeta. Linear model analyses adjusted
      for baseline cognitive function indicated that relative to healthy older adults
      with low Abeta, adults with aMCI and high Abeta showed greater decline in working
      memory and in verbal and visual episodic memory at 18 months. Adults with aMCI
      and low Abeta also showed greater decline in working memory; however they did not
      evidence any decline in episodic memory at 18 months. The results of our study
      suggests that relative to healthy older adults and adults with aMCI with low
      Abeta, adults with aMCI and high levels of Abeta showed faster rates of decline
      on measures of episodic memory over 18 months, and this was approximately twice
      that observed previously for healthy older adults with high Abeta levels.

PMID- 23160012
TI  - Activities of lipogenic enzymes in subcutaneous adipose tissue are not increased
      in patients with chronic kidney failure.
AB  - INTRODUCTION: Since renal replacement therapy has started to be a routine
      procedure in chronic kidney disease (CKD), patients no longer die of end-stage
      renal disease (ESRD). Today, patients with CKD live longer and the most important
      causes of morbidity and mortality in this group are cardiovascular events. Lipid
      abnormalities, such as hypertriglyceridemia (HT), are an important factor of high
      cardiovascular risk in this group. It is known that HT is partially caused by
      inhibition of lipolysis, but it is also postulated that increased lipogenesis is
      another cause of HT. Previous studies performed in our center has provided
      evidence that lipogenesis is increased in the animal model of ESRD.  OBJECTIVES:
      The aim of this study was to investigate the activities of lipogenic enzymes in
      the subcutaneous white adipose tissue in patients with CKD. PATIENTS AND METHODS:
      The study was performed on 36 patients (17 women and 19 men). Patients with ESRD
      were divided into 2 groups: patients on conservative treatment in the
      prehemodialysis period (pre-HD group, n = 18) and patients on maintenance
      hemodialysis (HD group, n = 18). The control group consisted of 22 patients
      without ESRD. The activities of lipogenic enzymes in the subcutaneous white
      adipose tissue (fatty acid synthase, adenosine triphosphate citrate lyase, malic
      enzyme, glucose-6-phosphate dehydrogenase, and 6-phosphogluconate dehydrogenase)
      were assessed by spectrophotometry.  RESULTS: There were no statistically
      significant differences in the activities of lipogenic enzymes in a fat tissue
      sample between patients with ESRD and the control group. CONCLUSIONS: The results
      did not confirm increased lipogenesis in patients with ESRD.

PMID- 23160014
TI  - [New oral anticoagulants for the prevention of thromboembolism in atrial
      fibrillation: from clinical evidence to appropriate use].
AB  - The large amount of data on new oral anticoagulants deriving from the RE-LY,
      ROCKET AF and ARISTOTLE studies, the analysis of patient subgroups and the latest
      guidelines on atrial fibrillation (AF) issued by the major international
      cardiology societies created the need for this special issue. Regulatory approval
      and reimbursement within the National Healthcare System of these new oral
      anticoagulants for patients with AF at risk of stroke are expected to
      progressively modify anticoagulant therapy for most patients on warfarin
      treatment. This evolution in the therapeutic approach to AF is primarily driven
      by the improved efficacy and safety profile of these novel agents that results in
      reduced thromboembolic and bleeding risk, in addition to their ease of
      administration and freedom from laboratory monitoring. When anticoagulation is
      indicated, it is currently suggested to replace dose-adjusted warfarin with one
      of the new oral anticoagulants. Although no data from comparative studies among
      new anticoagulants are available, the assessment of their efficacy and safety
      profile will help clinicians to tailor therapy to individual patients by choosing
      the most effective drug at the appropriate dosage. This review describes
      different algorithms for the use of new oral anticoagulants in everyday clinical
      practice, also in AF patients with concomitant renal dysfunction, with a special
      focus on drug interactions and bleeding risk.

PMID- 23160013
TI  - The tandem intermolecular hydroalkoxylation/Claisen rearrangement.
AB  - The Au(I)-catalyzed intermolecular hydroalkoxylation of alkynes with allylic
      alcohols to provide allyl vinyl ethers that subsequently undergo Claisen
      rearrangement is reported. This new cascade reaction strategy facilitates the
      direct formation of gamma,delta-unsaturated ketones from simple starting
      materials in a single step.

PMID- 23160015
TI  - [Risk stratification for thromboembolism and antithrombotic prophylaxis in atrial
      fibrillation].
AB  - Atrial fibrillation (AF) is associated with a significantly high risk of stroke
      and systemic embolism (4.5%/year). Oral anticoagulant therapy (OAT) with warfarin
      (INR range 2.0-3.0) significantly reduces thromboembolic risk, whereas aspirin
      has poor efficacy. In patients with AF, several scoring systems, such as the
      CHADS2 and CHA2DS2-VASc scores, are currently used to stratify thromboembolic
      risk. The CHA2DS2-VASc score stratifies patients at intermediate-low
      thromboembolic risk more accurately than the CHADS2 score. The most recent
      European and US guidelines on AF have extended the indications for OAT, which is
      recommended not only for patients at high risk, but also for those at
      intermediate risk, with CHADS2 score >=1. However, in clinical practice underuse
      of OAT, suboptimal quality of anticoagulation, and frequent discontinuations of
      treatment are observed. Therefore, there is a great expectation for the new oral
      anticoagulants, in particular the direct thrombin inhibitor dabigatran etexilate
      and the factor Xa inhibitors rivaroxaban and apixaban, which are at least non
      inferior to warfarin and safer, and seem to be a suitable therapeutic alternative
      to the old warfarin.

PMID- 23160016
TI  - [Dabigatran as an alternative to warfarin for the prevention of thromboembolism
      in atrial fibrillation].
AB  - Atrial fibrillation (AF) is an independent major risk factor for stroke, and
      antithrombotic therapy is here recommended according to stratification of the
      patient's thromboembolic and hemorrhagic risks. Recent evidence is leading to the
      replacement of vitamin K antagonists, the efficacy of which in preventing stroke
      in AF is well established, with better tolerated and more manageable new
      anticoagulant drugs, with a lower risk of intracranial bleeding, no clear
      interactions with food, fewer interactions with medications, and no need for
      frequent laboratory monitoring and dose adjustments. Among new anticoagulants,
      dabigatran etexilate is a direct, competitive inhibitor of thrombin. It was
      evaluated for patients with AF in the RE-LY trial, showing lower rates of stroke
      and systemic embolism at a dose of 150 mg twice daily with similar rates of major
      hemorrhage compared with warfarin; and non-inferiority compared with warfarin for
      the prevention of stroke and systemic embolism at a dose of 110 mg twice daily,
      with lower rates of major bleeding. Beside dabigatran, oral factor Xa inhibitors
      are also emerging for the prevention of thromboembolic events in AF. Despite the
      obvious advantages of these new oral anticoagulants over vitamin K antagonists,
      further information is still needed on how to prioritize the patients deriving
      the greatest benefit from these novel agents on the basis of patient
      characteristics or drug pharmacokinetics. There is also a need for assessing
      their long-term efficacy and safety over decades in the real-world setting.

PMID- 23160017
TI  - [New oral anticoagulants: recommendations, precautions and perspectives for use].
AB  - In phase III studies, some oral inhibitors of both thrombin (dabigatran
      etexilate) and activated factor X (rivaroxaban, apixaban) have been employed as
      new anticoagulant drugs in patients with atrial fibrillation or acute coronary
      syndromes. Such new drugs have overcome a series of limitations of the standard
      of-care warfarin, and argue for the possibility of an easy, widespread use of
      anticoagulation in vascular medicine. However, to this end, we need information
      on management of bleeding in patients receiving these drugs. Dabigatran
      etexilate, rivaroxaban and apixaban affect major laboratory tests for clotting.
      However, at present we do not know whether and how this information may be
      clinically useful. Their high cost is another major issue, and newer
      pharmacoeconomic studies are needed to evaluate their cost-effectiveness ratio vs
      warfarin.

PMID- 23160018
TI  - Properties and application of a multichannel integrated circuit for low-artifact,
      patterned electrical stimulation of neural tissue.
AB  - OBJECTIVE: Modern multielectrode array (MEA) systems can record the neuronal
      activity from thousands of electrodes, but their ability to provide spatio
      temporal patterns of electrical stimulation is very limited. Furthermore, the
      stimulus-related artifacts significantly limit the ability to record the neuronal
      responses to the stimulation. To address these issues, we designed a multichannel
      integrated circuit for a patterned MEA-based electrical stimulation and evaluated
      its performance in experiments with isolated mouse and rat retina. APPROACH: The
      Stimchip includes 64 independent stimulation channels. Each channel comprises an
      internal digital-to-analogue converter that can be configured as a current or
      voltage source. The shape of the stimulation waveform is defined independently
      for each channel by the real-time data stream. In addition, each channel is
      equipped with circuitry for reduction of the stimulus artifact. MAIN RESULTS:
      Using a high-density MEA stimulation/recording system, we effectively stimulated
      individual retinal ganglion cells (RGCs) and recorded the neuronal responses with
      minimal distortion, even on the stimulating electrodes. We independently
      stimulated a population of RGCs in rat retina, and using a complex spatio
      temporal pattern of electrical stimulation pulses, we replicated visually evoked
      spiking activity of a subset of these cells with high fidelity. Significance.
      Compared with current state-of-the-art MEA systems, the Stimchip is able to
      stimulate neuronal cells with much more complex sequences of electrical pulses
      and with significantly reduced artifacts. This opens up new possibilities for
      studies of neuronal responses to electrical stimulation, both in the context of
      neuroscience research and in the development of neuroprosthetic devices.

PMID- 23160019
TI  - Preparation and characterization of ZnS:Tb,Gd and ZnS:Er,Yb,Gd nanoparticles for
      bimodal magnetic-fluorescent imaging.
AB  - As bimodal magnetic-fluorescent imaging agents, the preparation of ZnS:Tb,Gd and
      ZnS:Er,Yb,Gd nanoparticles via a facile homogeneous precipitation method is
      reported. The results show that these nanoparticles are almost spherical in shape
      with a diameter of 100-200 nm approximately and a major phase of wurtzite
      structured ZnS. The products can successfully label the human hepatocellular
      carcinoma (HepG2) cells and present low toxicity even at concentrations up to 5
      mg mL(-1). Additionally, for the ZnS:Er,Yb,Gd nanoparticles calcinated above 950 
      degrees C, NIR-to-visible up-conversion fluorescence were obtained, which is
      believed to be superior to traditional ZnS-based bioimaging agents with down
      conversion. In MRI studies, they reveal a longitudinal relaxivity rate (r(1)) of
      39.46 mM(-1) s(-1) and 57.8 mM(-1) s(-1), respectively, which are much larger
      than the conventional Gd-DTPA and currently reported Gd-base nanoparticles,
      suggesting great potential as MRI agents.

PMID- 23160020
TI  - Effects of semantic and acoustic context on nonword detection in children with
      hearing loss.
AB  - PURPOSE: Children with hearing loss (HL) are known to have smaller receptive
      vocabularies than children with normal hearing (NH). This may be due, in part, of
      their reduced exposure to new words and their slower rate of word learning. A
      necessary prerequisite to lexical development is the detection of new words in
      conversation. The purpose of this study was to examine the effects of HL on
      children's ability to detect the presence of nonwords within sentences that
      varied in semantic and acoustic context. METHODS: Twenty-nine children with NH
      and 16 children with HL between the ages of 7 and 13 years participated. The
      children listened to short sentences and reported the number of nonwords
      detected, ranging from zero to two nonwords, in each sentence. The structure of
      the sentences was either meaningful or nonsensical to the children to reveal the
      effects of semantic context. The effects of acoustic context were revealed by
      presenting the sentences in quiet, steady-state noise, and in multi-talker
      babble. RESULTS: Significant effects of age (older > younger), hearing (NH > HL),
      and listening condition (quiet > noise and babble) were observed. Also, nonword
      detection was better for semantically meaningful sentences than for nonsense
      sentences. Error analyses revealed that the children with NH tended to
      underestimate the number of nonwords in meaningful sentences but not in nonsense
      sentences. The children with HL, however, were more likely to underestimate the
      number of nonwords than were the children with NH for both meaningful and
      nonsense sentences. These error patterns were observed in each listening
      condition. CONCLUSIONS: Error patterns suggest that children with HL apply strong
      repair strategies during speech perception, which may limit their opportunities
      to learn new words.

PMID- 23160021
TI  - Host-parasite interactions in a fragmented landscape.
AB  - Theory suggests that habitat fragmentation should reduce the risk of being
      parasitised due to reduced size and increased isolation of the host population.
      It is predicted that a threshold host population size exists, below which
      parasites will not be able to persist. Small mammals were trapped and their ecto
      parasites removed in 14 field margins of varying widths over 2 years in a highly
      fragmented agro-ecosystem. No evidence to suggest the presence of a threshold in
      parasite prevalence was found, which may be due to the high rate of host movement
      and transiency within the system. Contrary to expectation, the probability of
      infestation decreased with host abundance and the abundance of alternative hosts,
      suggesting a dilution effect. The relatively long life cycle of small mammal
      specialist tick and flea species present under the prevailing environmental
      conditions may have left the parasites unable to keep up with the rate of
      reproduction and dispersal of the host. It is important to consider changes in
      the behaviour of the host and the presence of alternative hosts when predicting
      the effects of habitat fragmentation on disease spread.

PMID- 23160022
TI  - Novel tools for the diagnosis and differentiation of acute and chronic bovine
      besnoitiosis.
AB  - Diagnosis of acute bovine besnoitiosis is a major diagnostic problem. We
      developed diagnostic tests to serologically diagnose and differentiate acute and
      chronic cases of bovine besnoitiosis using affinity purified antigens of
      Besnoitia besnoiti tachyzoites in immunoblots and in both, a conventional ELISA
      and an avidity ELISA. Sera of acutely and chronically infected cattle were
      investigated using these tests. Acutely infected cattle initially recognised an
      antigen of 74 kDa relative molecular mass, followed by reactions with increasing
      intensity against 81 and 28 kDa antigens. In addition, faint reactions against
      antigens with 36, 37, 39 and 42 kDa molecular mass started soon after
      seroconversion and increased over time. An antigen of 45 kDa molecular mass was
      transiently recognised early after infection but not or only weakly in the
      chronic stage. At least two antigens, the 39 and the 42 kDa antigens, seem to be
      located on the surface of B. besnoiti tachyzoites as determined by biotinylation.
      Affinity purified antigen was used to establish an APure-BbELISA which showed
      excellent sensitivity (100%) relative to a serological reference system in
      naturally, most likely chronically, infected cattle. Specificity was also high
      (99.8%) as determined in cattle from herds with Neospora caninum-associated
      abortions. The antibody levels in APure-BbELISA were correlated with the parasite
      load in the skin or the mucous membrane of the vestibulum vaginae as determined
      by real-time PCR. In acute cases of bovine besnoitiosis (confirmed by the
      detection of low avidity IgG in the APure-BbELISA) first specific antibodies were
      detected by ELISA in all animals except one, at the same time or earlier than in
      the serological reference system. The detection of parasite DNA in skin by real
      time PCR was clearly superior to serological analysis in detecting infected
      cattle during acute besnoitiosis.

PMID- 23160023
TI  - Downregulation of the small GTPase ras-related nuclear protein accelerates
      cellular ageing.
AB  - BACKGROUND: The small GTPase Ran, Ras-related nuclear protein, plays important
      roles in multiple fundamental cellular functions such as nucleocytoplasmic
      transport, mitotic spindle assembly, and nuclear envelope formation, by binding
      to either GTP or GDP as a molecular switch. Although it has been clinically
      demonstrated that Ran is highly expressed in multiple types of cancer cells and
      specimens, the physiological significance of Ran expression levels is unknown.
      METHODS: During the long-term culture of normal mammalian cells, we found that
      the endogenous Ran level gradually reduced in a passage-dependent manner. To
      examine the physiological significance of Ran reduction, we first performed small
      interfering RNA (siRNA)-mediated abrogation of Ran in human diploid fibroblasts.
      RESULTS: Ran-depleted cells showed several senescent phenotypes. Furthermore, we
      found that nuclear accumulation of importin alpha, which was also observed in
      cells treated with siRNA against CAS, a specific export factor for importin
      alpha, occurred in the Ran-depleted cells before the cells showed senescent
      phenotypes. Further, the CAS-depleted cells also exhibited cellular senescence.
      Indeed, importin alpha showed predominant nuclear localisation in a passage
      dependent manner. CONCLUSIONS: Reduction in Ran levels causes cytoplasmic
      decrease and nuclear accumulation of importin alpha leading to cellular
      senescence in normal cells. GENERAL SIGNIFICANCE: The amount of intracellular Ran
      may be critically related to cell fate determination, such as malignant
      transformation and senescence. The cellular ageing process may proceed through
      gradual regression of Ran-dependent nucleocytoplasmic transport competency.

PMID- 23160024
TI  - Changes in Borrelia burgdorferi ELISA antibody over time in both antibiotic
      treated and untreated horses.
AB  - Changes in ELISA serology are frequently used to determine antibiotic treatment
      success for Lyme disease in horses. This concept was based upon a previous report
      showing a marked decline in ELISA values in experimentally infected and
      antibiotic-treated ponies. Changes in Lyme serology following antibiotic
      treatment in naturally infected horses have not been reported. The objective of
      this study was to compare Borrelia ELISA antibody concentrations in naturally
      exposed horses both before and following antibiotic treatment for Lyme disease. A
      retrospective study was performed comparing oxytetracycline- or
      doxycyclinetreated (n = 68) and untreated (n = 183) horses from a single equine
      practice and their change in Borrelia ELISA values over a similar time period.
      Antibiotictreated horses had a decline in ELISA values in comparison to control
      horses (P <= 0.05) and untreated horses were twice as likely to have their ELISA
      values increase (OR = 0.5; 95% C.I. = 0.3-0.9) compared to treated horses. The
      magnitude of the decline in ELISA units following treatments was small compared
      to that previously reported in experimentally infected and treated ponies. Field
      exposed horses with high Borrelia burgdorferi ELISA values who are treated with
      either oxytetracycline or doxycycline can be expected to have only a small
      decline in ELISA values following treatment. Persistently high ELISA titres
      following appropriate treatments for Lyme disease may not, without appropriate
      clinical signs, be a reason for more prolonged treatment.

PMID- 23160025
TI  - Plasmid DNA could be delivered into Eimeria maxima unsporulated oocyst with gene
      gun system.
AB  - Eimerian coccidia are the most common parasitic organisms infecting chickens. The
      feasibility of genetic manipulation of these parasites via electroporation is
      proven, but this method is cumbersome and time consuming. Here we report our
      endeavour to develop a rapid and simple transfection method by gene gun. Tungsten
      particles coated with plasmid DNA encoding enhanced yellow fluorescent protein
      (EYFP) were used for the bombardment of Eimeria maxima unsporulated oocysts.
      Seven Mpa (1015 psi) helium pressure, 65 mm target distance and -0.098 Mpa (24.8"
      Hg) chamber vacuum were the optimised parameters for bombardment. After
      sporulation, the bombarded oocysts were inoculated into chickens, and the progeny
      oocysts were checked under fluorescent microscope and subjected to genomic DNA
      extraction, which was used either for polymerase chain reaction (PCR)
      amplification or plasmid rescue assay. Although the expression of EYFP was not
      observed, the gene was amplified from both genomic DNA and the rescued plasmid,
      suggesting that the plasmid DNA existed in the form of episome. These results are
      encouraging for the genetic processing of the sporogony stage of eimerian
      parasites.

PMID- 23160026
TI  - Evidence of Anaplasma phagocytophilum in game animals from Slovenia.
AB  - Anaplasma phagocytophilum is a tick-borne rickettsial pathogen responsible for
      granulocytic anaplasmosis in mammalian hosts including humans. Wild animals may
      play an important role in the epidemiology of this disease. The aim of this study
      was to estimate the prevalence of infection with A. phagocytophilum among
      wildlife in Slovenia. Serum samples (n = 376) from the most important game
      species [red deer (Cervus elaphus), roe deer (Capreolus capreolus), wild boar
      (Sus scrofa), chamois (Rupicapra rupicapra) and brown bear (Ursus arctos)] were
      examined by A. phagocytophilum-specific indirect fluorescent-antibody assay (IFA)
      and wild boar spleen samples (n = 160) were tested by polymerase chain reaction
      (PCR). A. phagocytophilum-specific antibodies were found in 72% of sera and A.
      phagocytophilum DNA was present in 6.2% of spleens. The data indicate that A.
      phagocytophilum is present and widespread in Slovenian game animals and that game
      species are involved in the natural life cycle of A. phagocytophilum.

PMID- 23160028
TI  - Adenoma of the cloacal scent gland in a California Kingsnake (Lampropeltis
      getulus californiae).
AB  - A multiple simple adenoma causing severe distortion of the tail base was
      identified in the cloacal scent gland of a female California Kingsnake
      (Lampropeltis getulus californiae). In addition to the normal epithelial layer of
      the gland and the skin, the tumour cells in the glandular epithelium also showed
      cross immunereactivity with humanised anti-cytokeratin antibody. This is the
      first description of an adenoma in the scent gland of a reptile species. Neither
      epithelial nor mesenchymal tumours arising from the scent gland of reptiles have
      been reported previously. This report also highlights the possible use of
      humanised antibodies on reptile species for the fast, reliable and specific
      differential diagnosis of tumours.

PMID- 23160027
TI  - Beta-catenin expression in pilomatrix carcinoma with multiple visceral metastases
      in a dog.
AB  - Beta-catenin is a protein initially identified as a submembrane component of the
      E-cadherin-mediated cell-to-cell adhesion system. It plays a role as a
      transcriptional factor in the wingless/Wnt signalling pathway. Beta-catenin has
      been associated with oncogenic activity in human benign and malignant pilomatrix
      neoplasms where the immunohistochemical profile of beta-catenin expression
      displayed both nuclear and cytoplasmic staining in basaloid cells. In this study,
      an 8-year-old female Irish setter dog was examined because of the presence of
      skin nodules. Tissue biopsies from different nodules were obtained and
      histological examination suggested a diagnosis of pilomatrix carcinoma. The dog
      spontaneously died after 2 months and necropsy showed multiple metastases in the
      nasal cavity, lungs, heart, kidney, liver and colon. Routine histopathology of
      metastatic sites showed features consistent with the pattern of primary
      neoplastic nodules. Immunohistochemical detection of beta-catenin was performed
      in both the primary tumour and the metastases. Beta-catenin expression was
      located in the nuclei, cytoplasm and membrane of squamoid cells and in the
      cytoplasm of basaloid cells, while shadow cells were completely negative. To the
      best of our knowledge, these data represent the first report on the
      immunohistochemical expression profile of beta-catenin in canine pilomatrix
      carcinoma.

PMID- 23160029
TI  - Effects of tylosin, tilmicosin and tulathromycin on inflammatory mediators in
      bronchoalveolar lavage fluid of lipopolysaccharide-induced lung injury.
AB  - The aim of this study was to determine the anti-inflammatory effects of
      macrolides through kinetic parameters in bronchoalveolar lavage fluid (BALF) of
      lipopolysaccharide-induced lung injury. Rats were divided into four groups:
      lipopolysaccharide (LPS), LPS + tylosin, LPS + tilmicosin and LPS +
      tulathromycin. BALF samples were collected at sampling times. TNF, IL-1beta, IL
      6, IL-10 and 13,14-dihydro-15-keto-prostaglandin F2alpha (PGM) and C-reactive
      protein (CRP) were analysed. Area under the curve (AUC) and maximum plasma
      concentration (Cmax) values of inflammatory mediators were determined by a
      pharmacokinetic computer programme. When inflammatory mediator concentrations
      were compared between the LPS group and other groups for each sampling time, the
      three macrolides had no pronounced depressor effect on cytokine levels, but they
      depressed PGM and CRP levels. In addition, tylosin and tilmicosin decreased the
      AUC0-24 level of TNF, while tilmicosin decreased the AUC0-24 level of IL-10.
      Tylosin and tulathromycin decreased the AUC0-24 of PGM, and all three macrolides
      decreased the AUC0-24 of CRP. Especially tylosin and tulathromycin may have more
      expressed anti-inflammatory effects than tilmicosin, via depressing the
      production of inflammatory mediators in the lung. The AUC may be used for
      determining the effects of drugs on inflammation. In this study, the
      antiinflammatory effects of these antibiotics were evaluated with kinetic
      parameters as a new and different approach.

PMID- 23160030
TI  - Blood corticosterone levels in growing geese around feather gathering.
AB  - Feather production is realised by gathering feathers from geese right as they
      start their natural moulting. The adequate gathering time coincides with the time
      of moulting. There is still scarce information as to whether or not gathering
      causes distress and pain to geese. A series of experiments was carried out by our
      research group to determine the effect of gathering on plasma corticosterone
      level in growing geese. In the present experiment, the reactions of five groups
      (two gathered and three not gathered groups) of 9-week-old Babat Hungarian
      Upgraded geese were compared regarding gathering. Blood samples were taken right
      before, during and 5 min, 1 and 3 h after gathering into heparinised tubes from
      all groups. The plasma concentration of corticosterone was determined by
      radioimmunoassay (RIA). The results show that the plasma concentration of
      corticosterone is high in the first sample of all groups but is significantly
      lower at subsequent blood samplings compared to the first samples, especially in
      gathered geese. Compared to the first sampling, we observed higher corticosterone
      levels in samples collected 1 and 3 h after gathering. This was true only for
      groups which were not gathered, especially for the group which was not given any
      antistress material. From these results it can be concluded that the handling of
      geese causes an elevation in plasma corticosterone level and that feather
      gathering does not result in a higher corticosterone level than the handling or
      catching of the bird. Therefore, it can be concluded that feather gathering -
      especially when it is done adequately in time - does not cause more distress than
      the handling or catching of the bird.

PMID- 23160031
TI  - Serum adiponectin concentration in dogs - absence of diurnal variation and lack
      of effect of feeding and methylprednisolone administration.
AB  - The aim of the study was to determine the magnitude of diurnal variability of
      serum adiponectin in healthy beagle dogs, and the possible roles of feeding and
      glucocorticoids on adiponectin concentrations. For this, adiponectin was measured
      at 8:00, 10:00, 12:00, 16:00, 20:00, 24:00 and at 4:00 h in 4 beagle dogs that
      were fasted on the day of the experiment and in 4 dogs that were fed as usual at
      9:00 h. Diurnal variability in serum adiponectin concentrations was negligible in
      both the fed and the fasted dogs. To study the possible effect of glucocorticoids
      on adiponectin, beagle dogs (n = 14) were assigned to one of three experimental
      groups. Dogs of the control group were injected with 0.1 ml/kg 0.9% NaCl
      subcutaneously, while dogs of Groups 1 and 2 were injected with 1 mg/kg and 5
      mg/kg of methylprednisolone, respectively, and adiponectin was measured at 8:00,
      10:00, 12:00, 16:00 and 20:00 h. Average serum adiponectin levels were not
      significantly different before and after methylprednisolone exposure at different
      time-points in the two treated groups. In conclusion, no evidence of postprandial
      changes in adiponectin level or effects of single-dose glucocorticoid
      administration on adiponectin were observed in the present study.

PMID- 23160032
TI  - Vitrification of early avian blastodermal cells with a new type of cryocontainer.
AB  - Although cryopreservation of avian semen is only applicable for singlegene
      traits, cryopreservation of avian blastodermal cells could facilitate
      preservation of the entire genome of endangered or rare-breed poultry. Slow
      freezing methods result in acceptable survival rates; however, there are
      apparently no reports regarding the use of vitrification. The aim of the study
      was to establish methods for chicken embryonic cell vitrification, including
      development of a container which supported cryopreservation of large numbers of
      cells (to increase the probability of chimera production). Based on a preliminary
      study, vitrification seemed to be practical for avian blastodermal cell
      preservation. Pieces of mosquito net as carrier increased live cell rates
      compared to pellet form in media containing two macromolecules. Furthermore, we
      concluded that fetal calf serum in the vitrification medium could be replaced by
      polyvinylpyrrolidone, a chemically defined substance free of unwanted growth
      factors and potential pathogens.

PMID- 23160033
TI  - Use of a deslorelin implant for influencing sex hormones and male behaviour in a
      stallion - Case report.
AB  - This case report describes the use of a subcutaneously applied 4.7-mg deslorelin
      acetate implant in a three-year-old Arabian crossbred stallion showing unwanted
      strong male behaviour. Following deslorelin acetate implantation the stallion
      showed a short transitional increase in male behaviour. A 'gelding-like'
      behaviour was noted 15 days (D15) after treatment. The horse was surgically
      castrated at the owners request at D52 after treatment. Serum testosterone,
      oestradiol-17beta and oestrone sulphate values decreased after deslorelin acetate
      implantation, but serum LH and FSH levels remained unchanged. Histopathological
      analysis of both testes and sperm analysis revealed a reduced spermatogenesis at
      D52. The testicular volume decreased after treatment. The use of a subcutaneously
      applied deslorelin acetate implant might be a promising tool to change the
      behaviour of aggressive stallions.

PMID- 23160034
TI  - Molecular characterisation of ovine herpesvirus type 2 (OvHV-2) in Turkey.
AB  - In this study, the physical examination of 22 cattle revealed clinical signs of
      malignant catarrhal fever (MCF). Peripheral blood leukocyte (PBL) samples of the
      22 cattle, and nasal (n = 7) and conjunctival (n = 9) swab samples from 16 sheep
      from two different farms, were taken for laboratory examination. The clinical
      diagnosis of MCF in cows was confirmed by the detection of ovine herpesvirus type
      2 (OvHV-2) DNA by polymerase chain reaction (PCR). OvHV-2 DNA was detected by
      nested-PCR in PBL of one cow with clinical signs and nasal (1/7)
      conjunctival(1/9) swab samples of two sheep housed in the same barn. According to
      the sequence analysis, three slightly divergent viruses were detected. The
      results indicate the need for additional research in different regions of Turkey
      to gain a better understanding of the incidence of MCF and its implications for
      the livestock industry.

PMID- 23160035
TI  - Book reviews.

PMID- 23160036
TI  - Influence of implant number on the biomechanical behaviour of mandibular implant
      retained/supported overdentures: a three-dimensional finite element analysis.
AB  - OBJECTIVE: The aim of this study was to evaluate strain distribution in peri
      implant bone, stress in the abutments and denture stability of mandibular
      overdentures anchored by different numbers of implants under different loading
      conditions, through three-dimensional finite element analysis (3D FEA). METHODS:
      Four 3D finite element models of mandibular overdentures were established, using
      between one and four Straumann implants with Locator attachments. Three types of
      load were applied to the overdenture in each model: 100N vertical and inclined
      loads on the left first molar and a 100N vertical load on the lower incisors. The
      biomechanical behaviours of peri-implant bone, implants, abutments and
      overdentures were recorded. RESULTS: Under vertical load on the lower incisors,
      the single-implant overdenture rotated over the implant from side to side, and no
      obvious increase of strain was found in peri-implant bone. Under the same loading
      conditions, the two-implant-retained overdenture showed more apparent rotation
      around the fulcrum line passing through the two implants, and the maximum
      equivalent stress in the abutments was higher than in the other models. In the
      three-implant-supported overdenture, no strain concentration was found in
      cortical bone around the middle implant under three loading conditions.
      CONCLUSIONS AND CLINICAL SIGNIFICANCE: Single-implant-retained mandibular
      overdentures do not show damaging strain concentration in the bone around the
      only implant and may be a cost-effective treatment option for edentulous
      patients. A third implant can be placed between the original two when patients
      rehabilitated by two-implant overdentures report constant and obvious denture
      rotation around the fulcrum line.

PMID- 23160037
TI  - A 3-day randomised clinical study investigating the efficacy of two toothpastes,
      designed to occlude dentine tubules, for the treatment of dentine
      hypersensitivity.
AB  - OBJECTIVES: A product comparison study to compare the short term clinical
      efficacy of a strontium acetate/silica toothpaste with an arginine/calcium
      carbonate paste for pain reduction in dentine hypersensitivity. METHODS: The
      study was examiner blind of two arm parallel design. Eighty healthy adult
      subjects from general dental practice with >=2 sensitive teeth but otherwise good
      oral health, were enrolled and randomised to 1 of 2 toothpaste treatments,
      schedule provided by the sponsor. Almost equal numbers received each treatment.
      Tooth sensitivity was measured in three ways; evaporative (Schiff score; Visual
      Analogue Scale) and tactile stimuli (Yeaple probe), prior to and immediately
      after subjects' self application of a single pea sized dose of toothpaste, and
      following subsequent twice daily brushing for three days with the paste. RESULTS:
      All 80 subjects completed the study. Results confirm that for both treatments,
      pain was reduced immediately and relief was sustained after 3 days use. For all 3
      measures, benefit was similar between the two pastes, with no statistical or
      clinical difference demonstrated, apart from response to evaporative stimulus at
      3 days, where Schiff scores were significantly lower in the arginine group,
      p=0.02. CONCLUSIONS: It can be concluded that both desensitising, occluding
      toothpastes provided reduction of pain from dentine hypersensitivity on a short
      term basis: toothpastes appearing to be clinically similarly effective both after
      a single subject dab on application and post twice daily brushing for three days.
      National Research Ethics Service register number 09/H020/57.

PMID- 23160038
TI  - A randomised controlled trial to investigate the effects of dehydration on tooth
      colour.
AB  - OBJECTIVES: To assess effects of dehydration on tooth colour. To investigate any
      change in tooth colour resulting from dehydration and the time required for any
      change to return to baseline. METHODS: 20 subjects with intact maxillary central
      incisors were recruited. In each case one incisor was randomly assigned as test
      tooth with the other acting as control. Spectrophotometric shade of the test
      teeth was assessed before dehydration and after rubber dam isolation every 10min
      for 30min. Test teeth were allowed to rehydrate and measurements taken every
      10min for 30min. Data was collected in CIE L*a*b* colour coordinates. A panel of
      10 examiners assessed before and after dehydration digital images of the control
      and test teeth. The panel judged whether central incisors were of same or
      different shade and which tooth was lighter if a difference was detected.
      RESULTS: All colour coordinates showed significant differences between baseline
      versus 10, 30min of dehydration and 30min of rehydration (p<0.02) except L* after
      30min rehydration. The panel found test and control teeth to be of same shade
      before and of different shade after dehydration (p<0.001). Test teeth were
      significantly lighter after dehydration (p<0.005). CONCLUSION: A significant
      change in shade of teeth when dehydrated was detected by both instrumental and
      visual assessment. Teeth became lighter and perceivable colour change had not
      returned to baseline shade within 30min of rehydration. Therefore shade matching
      procedures should be carried out before the teeth are exposed to dehydration.
      CLINICAL SIGNIFICANCE: As most dental procedures lead to dehydration of teeth
      which can alter their shade and may lead to errors in shade matching. To avoid
      unacceptable mismatch of colour between natural teeth and dental restoration it
      is important that the shade matching procedure is carried out at the beginning of
      the appointment.

PMID- 23160040
TI  - Insulin promotes iron uptake in human hepatic cell by regulating transferrin
      receptor-1 transcription mediated by hypoxia inducible factor-1.
AB  - Hepatic iron is known to regulate insulin signaling pathways and to influence
      insulin sensitivity in insulin resistance (IR) patients. However, the role of
      insulin on hepatic iron homeostasis remains unexplored. Here, we report that
      insulin promotes transferrin-bound iron uptake but shows no influence on non
      transferrin-bound iron uptake in human hepatic HepG2 cells. As a mechanism we
      detected increased transferrin receptor-1 (TfR1) expression both at protein and
      mRNA levels. Unaltered stability of protein and transcript of TfR1 suggested the
      regulation at transcriptional level that was confirmed by promoter activity.
      Involvement of transcription factor hypoxia inducible factor-1 (HIF-1) was shown
      by mutational analyses of the TfR1 promoter region and by electrophoretic
      mobility shift assay. When HepG2 cells were transfected with specific siRNA
      targeted to 3'UTR of HIF-1alpha, the regulatory subunit of HIF-1; insulin-induced
      TfR1 expression and iron uptake were inhibited. Transfection of cDNA expressing
      stable form of HIF-1alpha reversed the increased TfR1 expression and iron uptake.
      These results suggest a novel role of insulin in hepatic iron uptake by a HIF-1
      dependent transcriptional regulation of TfR1.

PMID- 23160041
TI  - Enhancing CO2 adsorption of a Zn-phosphonocarboxylate framework by pore space
      partitions.
AB  - Using structure-directing agents, pore space partitions of a Zn
      phosphonocarboxylate framework have been achieved. Selective adsorption of CO(2)
      over N(2) has been greatly improved from ca. 9 : 1 to 94 : 1.

PMID- 23160042
TI  - Correlated input reveals coexisting coding schemes in a sensory cortex.
AB  - As in other sensory modalities, one function of the somatosensory system is to
      detect coherence and contrast in the environment. To investigate the neural bases
      of these computations, we applied different spatiotemporal patterns of stimuli to
      rat whiskers while recording multiple neurons in the barrel cortex. Model-based
      analysis of the responses revealed different coding schemes according to the
      level of input correlation. With uncorrelated stimuli on 24 whiskers, we
      identified two distinct functional categories of neurons, analogous in the
      temporal domain to simple and complex cells of the primary visual cortex. With
      correlated stimuli, however, a complementary coding scheme emerged: two distinct
      cell populations, similar to reinforcing and antagonist neurons described in the
      higher visual area MT, responded specifically to correlations. We suggest that
      similar context-dependent coexisting coding strategies may be present in other
      sensory systems to adapt sensory integration to specific stimulus statistics.

PMID- 23160043
TI  - A high-performance neural prosthesis enabled by control algorithm design.
AB  - Neural prostheses translate neural activity from the brain into control signals
      for guiding prosthetic devices, such as computer cursors and robotic limbs, and
      thus offer individuals with disabilities greater interaction with the world.
      However, relatively low performance remains a critical barrier to successful
      clinical translation; current neural prostheses are considerably slower, with
      less accurate control, than the native arm. Here we present a new control
      algorithm, the recalibrated feedback intention-trained Kalman filter (ReFIT-KF)
      that incorporates assumptions about the nature of closed-loop neural prosthetic
      control. When tested in rhesus monkeys implanted with motor cortical electrode
      arrays, the ReFIT-KF algorithm outperformed existing neural prosthetic algorithms
      in all measured domains and halved target acquisition time. This control
      algorithm permits sustained, uninterrupted use for hours and generalizes to more
      challenging tasks without retraining. Using this algorithm, we demonstrate
      repeatable high performance for years after implantation in two monkeys, thereby
      increasing the clinical viability of neural prostheses.

PMID- 23160044
TI  - BCL6 controls neurogenesis through Sirt1-dependent epigenetic repression of
      selective Notch targets.
AB  - During neurogenesis, neural stem/progenitor cells (NPCs) undergo an irreversible
      fate transition to become neurons. The Notch pathway is important for this
      process, and repression of Notch-dependent Hes genes is essential for triggering
      differentiation. However, Notch signaling often remains active throughout
      neuronal differentiation, implying a change in the transcriptional responsiveness
      to Notch during the neurogenic transition. We identified Bcl6, an oncogene, as
      encoding a proneurogenic factor that is required for proper neurogenesis of the
      mouse cerebral cortex. BCL6 promoted the neurogenic conversion by switching the
      composition of Notch-dependent transcriptional complexes at the Hes5 promoter.
      BCL6 triggered exclusion of the co-activator Mastermind-like 1 and recruitment of
      the NAD(+)-dependent deacetylase Sirt1, which was required for BCL6-dependent
      neurogenesis. The resulting epigenetic silencing of Hes5 led to neuronal
      differentiation despite active Notch signaling. Our findings suggest a role for
      BCL6 in neurogenesis and uncover Notch-BCL6-Sirt1 interactions that may affect
      other aspects of physiology and disease.

PMID- 23160046
TI  - [Separation anxiety disorder:  evidence of literature and clinical implications].
AB  - Since the mid-90s several studies have proven the existence of an Adult form of
      the Separation Anxiety Disorder (ASAD) not yet nosologically recognized by the
      international psychiatric classification systems (DSM and ICD). An increasing
      amount of evidence showed that the separation anxiety disorder may arise at any
      age, not always in continuation with the correspondent childhood disorder. So, a
      revision of the diagnostic criteria for this disorder is brought into question,
      as the onset is currently limited before 18 years of age. Different tools have
      been developed for the assessment of ASAD: 1) the Adult Separation Anxiety
      Structured Interview (ASA-SI), a semi-structured interview with items derived and
      adapted from the DSM-IV-TR childhood disorder; 2) the Adult Separation Anxiety-27
      (ASA-27), a self-administered rating scale containing the same items of ASA-SI;
      3) the Structured Clinical Interview for Separation Anxiety Symptoms (SCI-SAS), a
      structured interview including two specific forms for childhood and adulthood.
      However, according to available evidence, the separation anxiety may be a
      dimension with cross-nosographical presentation in nearly all the commonest mood
      and anxiety disorders; moreover, it is connected to greater personal dysfunction
      and lower responsiveness to treatment. Furthermore, a deeper comprehension of the
      psychobiological nature of separation anxiety should lead to newer and more
      effective therapeutic intervention. Literature is reviewed awaiting the
      publication of DSM-V.

PMID- 23160045
TI  - Glucocorticoid receptors recruit the CaMKIIalpha-BDNF-CREB pathways to mediate
      memory consolidation.
AB  - Emotionally important events are well remembered. Although memories of emotional
      experiences are known to be mediated and modulated by stress hormones such as
      glucocorticoids, little is known about the underlying molecular mechanisms. We
      found that the hippocampal glucocorticoid receptors that are critically engaged
      during the formation of long-term inhibitory avoidance memory in rats were
      coupled to the activation of CaMKIIalpha, TrkB, ERK, Akt, PLCgamma and CREB, as
      well as a to a substantial induction of Arc and synaptic GluA1. Most of these
      changes, which are initiated by a nongenomic effect of glucocorticoid receptors,
      were also downstream of the activation of brain-derived neurotrophic factor
      (BDNF). Hippocampal administration of BDNF, but not of other neurotrophins,
      selectively rescued both the amnesia and the molecular impairments produced by
      glucocorticoid receptor inhibition. Thus, glucocorticoid receptors mediate long
      term memory formation by recruiting the CaMKIIalpha-BDNF-CREB-dependent neural
      plasticity pathways.

PMID- 23160047
TI  - Sleep and biorythm disturbances in schizophrenia, mood and anxiety disorders: a
      review.
AB  - Sleep problems and circadian rhythms disturbances are common in many psychiatric
      disorders, with the most often-reported sleep problem in most cases being
      insomnia. In this paper, the main findings about sleep disturbances(features and
      therapy) and other biorhythm disturbances (biological timekeepers, CLOCK genes,
      GSK3, melatonin, hypothalamo-pituitary-adrenal axis, body temperature) are
      reviewed in relation to schizophrenia, mood and anxiety disorders.

PMID- 23160048
TI  - [The post-traumatic embitterment disorder: clinical features].
AB  - BACKGROUND: In the last decade, post-traumatic embitterment disorder (PTED) has
      been internationally recognised as a specific form of adjustment disorder which
      arises after severe and negative, but not life threatening, life events
      (conflicts at work, unemployment, death of a relative, divorce, severe illness).
      More recent research on its specific symptomatologic features, its chronic
      course, and the difficulties of treatment, have lead to the definition of
      distinct diagnostic criteria for PTED. The aim of this paper is to describe its
      main clinical features for both diagnostic and therapeutic purposes. METHODS: The
      literature that is available allows to define specific psychopathological
      symptoms and etiology, and to distinguish PTED from post-traumatic stress,
      adjustment disorders and irritable mood. RESULTS AND CONCLUSIONS: PTED is a
      disorder with a specific psychopathological framework. The introduction of PTED
      in the diagnostic manuals of mental disorders would be of help to better diagnose
      the spectrum of disorders following negative life events.

PMID- 23160049
TI  - [Mental Health Centers, in regard to professional confidentiality and privacy].
AB  - Maintaining privacy in the complex operative reality of public psychiatric
      services is not easy. Many operational doubts arise and psychiatrists encounter
      difficulties in application of the privacy norms, partly due to the clinical and
      treatment peculiarities of the psychiatric domain and partly to organizational
      and structural limits. The risk addressed in this work is that the apparent
      complexity of the privacy norms may be perceived by psychiatrists in the public
      sector simply as a further bureaucratization of the doctor-patient relationship
      rather than as an opportunity to institute greater safeguards of patients'
      rights. Hence, the Authors aim to clarify the key points of the law, integrating
      them with the classic issues of confidentiality, in order to outline the goals,
      provide suggestions as to how best to adapt practice to conform to these norms,
      and highlight ways to simplify procedures. The Authors conclude by expressing the
      hope that the principles embodied in the privacy norms may become an integral
      part of the cultural heritage of territorial psychiatric services.

PMID- 23160050
TI  - The SDQ in Italian clinical practice: evaluation between three outpatient groups
      compared.
AB  - AIM: The aim of the study is to evaluate the effectiveness of the Strength and
      Difficulties Questionnaire (SDQ) as a screening tool for emotional and behavioral
      problems in three different populations at risk. METHODS: The SDQ is a brief
      screening questionnaire that investigates the presence of emotional and
      behavioural problems in children and adolescents. We have analyzed 497
      questionnaires completed by parents of children referred to Child
      Neuropsychiatry, Pediatric Endocrinology and Pediatric Oncology Units. RESULTS:
      Results indicate a higher presence of psychopathological disorders in
      Neuropsychiatry patients than Oncology and Endocrinology patients. Furthermore
      the Oncology patients have more emotional and behavioral problems than
      Endocrinology patients. DISCUSSION: The findings support the use of the SDQ
      questionnaire in the assessment of emotional and behavioral problems in these
      populations at risk. So the SDQ could be used by clinicians to detect early
      psychopathological disorder in children with different kind of chronic organic
      diseases.

PMID- 23160051
TI  - Premorbid circadian profile of patients with major depression and panic disorder.
AB  - AIMS: This study aims to compare some behavioural characteristics related to
      circadian functions in healthy subjects, in patients with major depressive
      disorder (MDD) and panic disorder (PD) during adulthood (disease period) and
      during the premorbid age (between 12 and 20 years old). METHODS: 132 adult
      patients with MDD, 144 with PD and 151 adult healthy controls were enrolled in
      the study. All subjects completed a retrospective questionnaire. RESULTS: Several
      behaviours (such as falling asleep, awakening, having, appetite, perceiving
      energy and cognitive functioning) showed a phase delay or a phase advance in MDD
      and PD patients compared to healthy controls. Behavioural differences where found
      in patients even before the clinical onset of the disease. CONCLUSIONS: Circadian
      profiles of MDD and PD patients diverge from those of healthy controls not only
      during the disorder but also in the ages preceding its clinical onset. The
      analysis of these circadian patterns may aid physicians to early identify
      subjects with specific psychiatric vulnerabilities.

PMID- 23160052
TI  - [Family violence and mental health in adolescence: complex trauma  as a
      developmental disorder].
AB  - AIM: To highlight the harmfulness and pervasive of early and repeated exposure to
      family violence from the theoretical perspective of complex trauma as a
      developmental disorder. METHOD: A study carried out on a sample of 22 adolescents
      between the ages of 15 and 18, who have been entrusted to Il Faro Bologna, a
      Specialist Centre for child abuse and neglect. Specific areas of psychological
      functioning were examined. According to the NCTSN these areas are considered
      vulnerable to violence in primary relationships and crucial for future mental
      health. They are attachment, self-concept, affect regulation, cognition and
      behavioural control. The data was correlated with the different forms of
      maltreatment and the main risk factors detected in the family environment and was
      collected by means of clinical interviews, family and social histories,
      structured interviews and self-reports recommended by the NASMHPD. RESULTS: The
      data highlights a correlation between the psychic functions examined and exposure
      to family violence, distortion of parental empathy and parental responsibility
      failure. CONCLUSION: The study indicates the need: a) to raise clinical awareness
      of the consequences of complex trauma on development; b) to adopt specific
      diagnostic tools for evaluating post-traumatic outcomes; c) to carry out regular
      screening in order to explore histories of maltreatment in patients cared for by
      mental health services.

PMID- 23160053
TI  - [Subtypes of psychotic-like experiences in a community sample of young adults:
      socio-demographic correlates and substance use].
AB  - AIM: This study aimed to investigate if particular psychotic-like experiences
      (PLEs) subtypes were more likely to be associated with a series of socio
      demographic variables, with alcohol abuse and with cannabis or illicit drug use.
      The idea is to further characterize different PLEs subtypes in order to discloud
      their individual nature. METHODS: A cross-sectional design was conducted on a
      sample of 997 university students aged between 19 and 26 years, which belonged to
      4 faculties of 2 different universities. Alcohol abuse and cannabis or illicit
      drug use were assessed using a self-report questionnaire; PLEs were assessed
      using the Community Assessment of Psychic Experiences. Cases were randomized in
      order to obtain equipotent groups; then, an analysis of the probable dependence
      relations between PLEs subtypes and other variables was conducted using analysis
      of variance models. RESULTS: Persecutory ideas (PI) and bizarre experiences were
      more frequent within females and non-resident students, moreover PI were more
      frequent within younger subjects (<20 years). Magical thinking was significantly
      associated to a more frequent cannabis use in the last year (>1/month).
      CONCLUSIONS: These results confirm usefulness and validity of a "subtype
      approach" to PLEs. In fact PLEs subtypes may have, not only a different clinical
      presentation, but even different epidemiological and psychopathological ones.

PMID- 23160054
TI  - [Promoting psychosocial well-being in adolescence. A controlled study].
AB  - INTRODUCTION: In the recent years a large body of literature has focused its
      attention to the study of the positive aspects of adolescence, in particular
      quality of life, happiness and social functioning. The school is an ideal setting
      for promoting learning abilities, educational processes and also optimal human
      and social development. AIM: A new school program for the promotion of
      psychological well-being has been tested and compared to an attention-placebo
      intervention in a high school setting. METHODS: Nine classes (227 students) were
      enrolled in the study and randomized to: a) School Well-Being Therapy
      intervention (5 classes); b)attention-placebo (4 classes). 1) Symptom
      Questionnaire (SQ); 2) Psychological Well-Being Scales (PWB); 3) Revised
      Children's Manifest Anxiety Scale (RCMAS) were administered at pre- and post
      intervention, and after six months. RESULTS: WBT school intervention was
      associated to an improved Personal Growth (PWB), and to decreased distress
      (Somatization (SQ), Physical Well-being (SQ), Anxiety (SQ), and RCMAS
      Physiological Anxiety). DISCUSSION AND CONCLUSIONS: A school intervention focused
      on the promotion of positive emotions and psychological well-being has resulted
      to be effective not only in increasing these dimensions in high school students,
      but also in decreasing distress, in particular anxiety and somatization.

PMID- 23160055
TI  - [Sensitive delusion of reference, rivisitation of a concept:  clinical accounts
      on onset paranoid psychosis].
AB  - AIM: In this work it is discussed whether and how Kretchmer's psychopathological
      reflections about sensitive delusion of reference can offer a relevant
      interpretative key for clinicians who face cases of acute persecutory psychosis.
      It is argued the utility and topicality of those psychopathological concepts that
      aren't commonly investigated, especially in the evaluation and management of
      onset paranoid psychosis in an emergency ward. METHODS: We provide clinical
      vignettes of two young patients, admitted in the emergency psychiatry ward, who
      represent a concrete example of the dynamic-affective comprehension of delusional
      elaboration, through its embodiment in the individual biographical development.
      RESULTS: An interpretative key, based on this specific conceptual frame, seems to
      provide an integrated intervention tool that aims both to a causal comprehension
      and demolition of the delusional solution in onset psychotic cases. CONCLUSIONS:
      The rediscovery of classical psychopathological concepts appears to be a
      necessary process, especially in the clinical management of onset psychotic
      disorders. Further and more accurate researches are, in any case, needed.

PMID- 23160056
TI  - Mood disorder with psychotic symptoms and overlooked skin lesions: the strange
      case of Mrs. O.
AB  - Here we report the case of Mrs. O., a 57 years-old woman presenting with mood
      disorder with psychotic symptoms developing strange skin lesions, ultimately
      leading to the suspected diagnosis of varicella-zoster encephalitis. The later
      appearance of a post-infectious acute inflammatory demyelinating
      polyradiculoneuropathy further confirmed the suspect. This case stresses the
      importance for not discarding a priori neurological diagnoses when facing with
      psychiatric patients, especially when atypical details are present.

PMID- 23160057
TI  - Increased expression of alpha2 (CD49b), alpha4 (CD49d) and beta1 (CD29) integrin
      subunits on peripheral blood T lymphocytes in clinically stable mild-to-moderate
      persistent asthma.
AB  - INTRODUCTION: Adhesive molecules, particularly selectins and integrins, are
      critical for the inflammatory cell trafficking from blood to the lungs. Among
      integrins, the most important for cell infiltration are those containing alpha4
      and beta2 subunits. OBJECTIVES: The aim of this study was to evaluate the
      expression of alpha1 and alpha2 integrin subunits on peripheral blood T cells in
      asthmatic subjects, because previously we showed evidence that alpha1beta1 and
      alpha2beta1 integrins may be found on peripheral blood eosinophils in these
      subjects. In this study, we also analyzed the expression of alpha4 and beta1
      subunits as a positive reference. PATIENTS AND METHODS: Expression of alpha1,
      alpha2, alpha4, and beta1 subunits was analyzed by flow cytometry on CD4+ and
      CD8+ T lymphocytes obtained from the peripheral blood of 54 clinically stable,
      asymptomatic, mild-to-moderate persistent asthmatics and 40 healthy controls.
      RESULTS: The alpha1 subunit was not present on peripheral blood T cells in the
      majority of subjects in both study groups. Expression of alpha2 was detectable on
      CD8+ cells in both groups and was increased on CD4+ in asthmatics. Both types of
      T cells showed higher expression of alpha4 and beta1 in patients with asthma.
      Expression of alpha4 was higher on CD8+ T cells both in asthmatics and controls.
      CONCLUSIONS: Expression of alpha4 and beta1 integrin subunits is increased on
      peripheral blood T cells in patients with asthma, which confirms the
      preactivation of blood lymphocytes even in stable and asymptomatic disease. The
      biological role of alpha2 subunit on T cells remains to be elucidated.

PMID- 23160058
TI  - Interactions of iron-sulfur clusters with small peptides: insights into early
      evolution.
AB  - Favoring the stability of iron-sulfur clusters in hydrothermal vents could have
      been important for the origin of life. It has been postulated that small "nest"
      peptides with lengths between 3 and 6 residues could have been important to
      stabilize early iron-sulfur clusters. We present theoretical calculations
      exploring the sequence and conformational spaces of short peptides able to bind
      with high affinity the iron-sulfur cluster Fe(4)S(4). Our results indicate that
      it is unlikely to form stable complexes between Fe(4)S(4) and small peptides at
      the core of hydrothermal vents. The formation of these complexes is instead
      favored for peptides of at least 8 residues as they diffused together with the
      Fe(4)S(4) clusters toward lower temperature regions within the vent-associated
      temperature gradients.

PMID- 23160059
TI  - Tetrahydroxystilbene glucoside antagonizes age-related alpha-synuclein
      overexpression in the hippocampus of APP transgenic mouse model of Alzheimer's
      disease.
AB  - PURPOSE: To investigate the mRNA and protein alterations of alpha-synuclein in
      the brain of Alzheimer's disease-like mouse model at the different ages, and to
      evaluate the effects of 2,3,5,4'-tetrahydroxy stilbene-2-O-beta-D-glucoside (TSG)
      on alpha-synuclein expression. METHODS: TSG (120 or 240 MUmol kg(-1)d(-1)) was
      intragastrically administered to APPV717I transgenic (Tg) mice at 4- or 10-month
      old for 6 months. RESULTS: mRNA expression of alpha-synuclein increased in
      hippocampus in 4 month to 16 month old Tg mice compared with age-matched control.
      alpha-synuclein protein expression in hippocampus also increased in 4 month to 16
      month old Tg mice significantly. Significant down-regulation of alpha-synuclein
      mRNA and protein expression in hippocampus was found after treatment of TSG for 6
      months in both 10- and 16-month-old Tg mice. Production of dimer and tetramer of
      alpha-synuclein protein in Tg mice was inhibited after treatment with TSG.
      CONCLUSIONS: The expression and aggregation of alpha-synuclein was age
      dependently increased in Tg mice. TSG not only prevents over-expression of alpha
      synuclein at an early stage, but also reverses the increased expression of alpha
      synuclein and inhibits the aggregation at the late stage of Tg mice. TSG may have
      potential to the prevention and treatment of Alzheimer's diseases.

PMID- 23160060
TI  - Neuroprotective effects of bacopaside I in ischemic brain injury.
AB  - PURPOSE: Bacopa monnieri (L.) WETTST. is extensively used in traditional Indian
      medicine as a nerve tonic. The neuropharmacological properties of bacopaside I,
      an important component from B. monnieri, have not been studied so far. The
      present study investigated the effects and possible mechanisms of bacopaside I in
      a rat model of transient focal ischemia induced by middle cerebral artery
      occlusion (MCAO). METHODS: Adult male Sprague-Dawley rats were divided into five
      groups: sham-operated group, ischemia group, and three bacopaside I-treated
      groups (3, 10 and 30 mg/kg) respectively. Bacopaside I or vehicle (0.5% CMC-Na)
      was administered orally once a day for 6 days. On the third day, the rats were
      subjected to 2 h right MCAO via the intraluminal filament technique and 70 h
      reperfusion. Assessment of behavioral deficits both at 22 and 70 h, and
      measurement of cerebral infarct volume, edema, cerebral energy metabolism,
      relative enzyme activities, malondialdehyde (MDA) content, nitric oxide (NO)
      level, and antioxidant enzyme activities at 70 h, performed after MCAO
      reperfusion. RESULTS: Bacopaside I (10 and 30 mg/kg) treatment produced
      significant reduction in neurological deficits at 22 and 70 h, and significantly
      reduced cerebral infarct volume and edema at 70 h, when compared with the
      ischemia group. Animal, that were orally treated with bacopaside I (3, 10 and 30
      mg/kg) showed increased the brain ATP content, energy charge (EC), total adenine
      nucleotides (TAN), nitric oxide (NO) level, Na+K+ATPase and Ca2+Mg2+ATPase
      activity. Bacopaside I (3, 10 and 30 mg/kg) treatment also improved antioxidant
      enzyme activities including brain superoxide dismutase (SOD), catalase (CAT),
      glutathione peroxidase (GSH-Px), in varying degrees, compared with the ischemia
      group. In addition, three doses of bacopaside I (3, 10 and 30 mg/kg) markedly
      inhibited the increase in MDA content of the brain. CONCLUSIONS: These findings
      indicated that bacopaside I possess a neuroprotective effect against injury
      caused by cerebral ischemia. The protective mechanism might be related to
      improving cerebral energy metabolism and increasing antioxidant levels.

PMID- 23160061
TI  - Wideband trapping of light by edge states in honeycomb photonic crystals.
AB  - We study theoretically light propagations at the zigzag edge of a honeycomb
      photonic crystal consisting of dielectric rods in air, analogous to graphene.
      Within the photonic band gap of the honeycomb photonic crystal, a unimodal edge
      state may exist with a sharp confinement of optical fields. Its dispersion can be
      tuned simply by adjusting the radius of the edge rods. For the edge rods with a
      graded variation in radius along the edge direction, we show numerically that
      light beams of different frequencies can be trapped sharply in different spatial
      locations, yielding wideband trapping of light.

PMID- 23160062
TI  - Population genomic analysis of base composition evolution in Drosophila
      melanogaster.
AB  - The relative importance of mutation, selection, and biased gene conversion to
      patterns of base composition variation in Drosophila melanogaster, and to a
      lesser extent, D. simulans, has been investigated for many years. However,
      genomic data from sufficiently large samples to thoroughly characterize patterns
      of base composition polymorphism within species have been lacking. Here, we
      report a genome-wide analysis of coding and noncoding polymorphism in a large
      sample of inbred D. melanogaster strains from Raleigh, North Carolina. Consistent
      with previous results, we observed that AT mutations fix more frequently than GC
      mutations in D. melanogaster. Contrary to predictions of previous models of codon
      usage in D. melanogaster, we found that synonymous sites segregating for derived
      AT polymorphisms were less skewed toward low frequencies compared with sites
      segregating a derived GC polymorphism. However, no such pattern was observed for
      comparable base composition polymorphisms in noncoding DNA. These results suggest
      that AT-ending codons could currently be favored by natural selection in the D.
      melanogaster lineage.

PMID- 23160065
TI  - The early detection research network: 10-year outlook.
AB  - BACKGROUND: The National Cancer Institute's Early Detection Research Network
      (EDRN) has made significant progress in developing an organized effort for
      discovering and validating biomarkers, building resources to support this effort,
      demonstrating the capabilities of several genomic and proteomic platforms,
      identifying candidate biomarkers, and undertaking multicenter validation studies.
      In its first 10 years, the EDRN went from a groundbreaking concept to an
      operational success. CONTENTS: The EDRN has established clear milestones for
      reaching a decision of "go" or "no go" during the biomarker development process.
      Milestones are established on the basis of statistical criteria, performance
      characteristics of biomarkers, and anticipated clinical use. More than 300
      biomarkers have been stopped from further development. To date, the EDRN has
      prioritized more than 300 biomarkers and has completed more than 10 validation
      studies. The US Food and Drug Administration has now cleared 5 biomarkers for
      various clinical endpoints. SUMMARY: The EDRN today combines numerous
      collaborative and multidisciplinary investigator-initiated projects with a strong
      national administrative and data infrastructure. The EDRN has created a rigorous
      peer-review system that ensures that preliminary data--analytical, clinical, and
      quantitative--are of excellent quality. The process begins with an internal
      review with clinical, biostatistical, and analytical expertise. The project then
      receives external peer review and, finally, National Cancer Institute program
      staff review, resulting in an exceptionally robust and high-quality validation
      trial.

PMID- 23160064
TI  - Communication of scientific information: is it time to reassess?

PMID- 23160063
TI  - Quantifying homologous replacement of loci between haloarchaeal species.
AB  - In vitro studies of the haloarchaeal genus Haloferax have demonstrated their
      ability to frequently exchange DNA between species, whereas rates of homologous
      recombination estimated from natural populations in the genus Halorubrum are high
      enough to maintain random association of alleles between five loci. To quantify
      the effects of gene transfer and recombination of commonly held (relaxed core)
      genes during the evolution of the class Halobacteria (haloarchaea), we
      reconstructed the history of 21 genomes representing all major groups. Using a
      novel algorithm and a concatenated ribosomal protein phylogeny as a reference, we
      created a directed horizontal genetic transfer (HGT) network of contemporary and
      ancestral genomes. Gene order analysis revealed that 90% of testable HGTs were by
      direct homologous replacement, rather than nonhomologous integration followed by
      a loss. Network analysis revealed an inverse log-linear relationship between HGT
      frequency and ribosomal protein evolutionary distance that is maintained across
      the deepest divergences in Halobacteria. We use this mathematical relationship to
      estimate the total transfers and amino acid substitutions delivered by HGTs in
      each genome, providing a measure of chimerism. For the relaxed core genes of each
      genome, we conservatively estimate that 11-20% of their evolution occurred in
      other haloarchaea. Our findings are unexpected, because the transfer and
      homologous recombination of relaxed core genes between members of the class
      Halobacteria disrupts the coevolution of genes; however, the generation of new
      combinations of divergent but functionally related genes may lead to adaptive
      phenotypes not available through cumulative mutations and recombination within a
      single population.

PMID- 23160066
TI  - The association of insulin-like growth factor-1 with severity of coronary artery
      disease.
AB  - AIM: Insulin-like growth factor-1 (IGF-1) has been identified as a valuable
      indicator for impaired glucose tolerance, and its relationship with the presence
      of coronary atherosclerosis has been also suggested. A few studies have assessed
      the relationship between IGF-1 level and severity of atherosclerosis. In the
      present study, the relationship between IGF-1 and coronary artery disease (CAD)
      was examined with particular attention to the association between this parameter
      and Gensini score as a good angiographic marker for determining extension and
      severity of CAD. METHODS: One hundred and seven patients with suspected CAD
      consecutively referred for selective coronary angiography at the Shafa Hospital
      in Kerman between April and September 2010 were prospectively enrolled. Total IGF
      1 was measured using radioimmunoassay methods (Diagnostics Systems Laboratory,
      Iran). Selective coronary angiography was performed for all study patients and
      the Gensini score is computed by assigning a severity score to each coronary
      stenosis according to the degree of luminal narrowing and its importance based on
      location. RESULTS: According to the Spearman correlation analysis, total IGF-I
      was directly correlated with Gensini score (Spearman's rho = 0.362, P = 0.041).
      Total IGF-I was slightly related to the number of involved coronary vessels (P =
      0.058). Relation between age-adjusted and sex-adjusted mean total IGF-I levels
      with Gensini score remained significant (P = 0.046); however, the association
      between IGF-1 and the number of diseased vessels lost statistical significance
      after this adjustment. CONCLUSION: IGF-1 appears as a positive indicator for
      severity of CAD assessed by the Gensini score, and thus its concentration may be
      an important indicator for assessing the extent of coronary artery involvement.

PMID- 23160070
TI  - DsRed-mediated oligomerization stabilizes HMGB1 on chromatin in vivo and on DNA
      in vitro.
AB  - High-mobility group box-1 (HMGB1) is remarkably mobile in living cells, which
      reflects its ability to interact only transiently with both DNA and protein. This
      property is likely essential for HMGB1 nuclear activities. Nonetheless the weak
      interaction of HMGB1 with DNA and/or protein partners has also been a major
      limitation for investigating HMGB1 subnuclear localisation and for the
      identification of HMGB1 containing complexes by conventional biochemical
      approaches. In the present study, FRAP experiments demonstrated that DsRed
      mediated oligomerization strongly reduces HMGB1 mobility due to an increased
      affinity for cellular chromatin. Moreover, oligomerized DsRed-HMGB1 exhibited a
      higher affinity for supercoiled DNA in vitro compared to its monomeric
      counterpart. These results indicate that DsRed-meditated oligomerization is prone
      to stabilize labile interactions involving HMGB1 both in vivo and in vitro.

PMID- 23160069
TI  - Norepinephrine inhibition in juvenile male zebra finches modulates adult song
      quality.
AB  - During development, male zebra finches learn a song that they eventually use in
      courtship and defense of nest sites. Norepinephrine (NE) is important for
      learning and memory in vertebrates, and this neuromodulator and its receptors are
      present throughout the brain regions that control song learning and production.
      The present study used the neurotoxin N-(2-chloroethyl)-N-ethyl-2
      bromobenzylamine hydrochloride (DSP4) to reduce brain levels of NE in juvenile
      males. This manipulation inhibited the development of quality songs, with some
      birds producing syllables that were unusually long and/or contained frequencies
      that were predominantly higher than normal. These results suggest that NE is
      important for the acquisition of typical song.

PMID- 23160071
TI  - Autoactivation of prolegumain is accelerated by glycosaminoglycans.
AB  - The cysteine protease legumain participates in several biological and
      pathological processes including tumour invasion and metastasis. Legumain is
      synthesized as a zymogen and undergoes pH-dependent autoactivation of the proform
      in order to reach an enzymatically active form. Here we demonstrate that the
      naturally occurring polyanionic glycosaminoglycans (GAGs) chondroitin 4-sulphate
      (C4S), chondroitin 6-sulphate (C6S), chondroitin 4,6-sulphate (C4,6S), heparin,
      heparan sulphate (HS) as well as chondroitin sulphate (CS)-derived
      decasaccharides accelerated the autocatalytic activation of prolegumain through
      ionic interactions in a concentration-, size- and time-dependent manner at pH
      4.0. In contrast, at pH 5.0 only C4S and C4,6S were able to promote prolegumain
      activation, while CS-derived decasaccharides, C6S, heparin and HS lost their
      effect at this pH.

PMID- 23160072
TI  - NF-kappaB, Sp1 and NF-Y as transcriptional regulators of human SND1 gene.
AB  - Staphylococcal nuclease domain-containing protein 1 (SND1), also called Tudor-SN,
      is required for many biological events ranging from gene expression to cell
      growth regulation. Promoter regulation of SND1 gene and its molecular mechanism
      have remained elusive to date. In this work, we have identified SND1 as a new
      target gene for NF-kappaB, Sp1 and NF-Y transcription factors. We isolated and
      characterized a 3808 bp sequence corresponding to the human SND1 gene promoter
      (GenBank ID: EF690304). It lacks the typical TATA-box element and contains a CpG
      island with several Sp1 binding sites at the 3' end, and a highly conserved 300
      bp segment with two inverted CCAAT boxes that bind NF-Y, in addition to NF-kappaB
      sites and other cis-regulatory elements. Electrophoretic mobility shift assays
      and chromatin immunoprecipitation experiments confirmed the ability of SND1
      promoter to bind NF-kappaB, Sp1 and NF-Y in vitro and in vivo. Deletion analysis
      of the 5'-flanking region by luciferase reporter assays, showed the minimum
      promoter activity 112 base-pair upstream from the transcription start site, and
      an enhancer region between -112 and -274 bp responsible for the maximal
      transcriptional activity of the promoter. Site-directed mutagenesis of the CCAAT
      and GC boxes and the NF-kappaB elements within the proximal region substantially
      reduced SND1 promoter activity. Proinflammatory cytokine TNF-alpha caused an
      increase of SND1 promoter activity that is mediated, at least in part, via NF
      kappaB as mutation in the NF-kappaB sites impaired the promoter stimulation. We
      provide for the first time the characterization of the human SND1 promoter
      activity and establish a transcriptional network associated to the key
      transcription factors NF-kappaB, Sp1 and NF-Y that operates in the control of the
      SND1 gene expression.

PMID- 23160075
TI  - [Clinical application of induced and spontaneous sputum in asthma and chronic
      obstructive pulmonary disease].
AB  - In recent years induced sputum analysis has become a non-invasive method for the
      assessment of airway inflammation in obstructive airway diseases. Sputum
      induction is safe and well tolerated by the patients. The method has been
      standardized, and this has markedly improved the quality and reproducibility of
      sputum samples. Identification of sputum eosinophilia has the greatest clinical
      relevance as it predicts a favorable response to corticosteroids. Treatment
      strategy aiming normalisation of sputum eosinophil cell count may reduce the rate
      of exacerbations in asthma. Profiling inflammatory mediators in sputum
      supernatant provides new insights into the pathogenesis of asthma and chronic
      obstructive pulmonary disease. Cell type analysis in spontaneous sputum may also
      provide much information about inflammatory processes in the airways. Based on
      the results of clinical studies sputum analysis should be more often used in
      clinical settings in the future.

PMID- 23160073
TI  - Biochemical, cellular and molecular identification of DNA polymerase alpha in
      yeast mitochondria.
AB  - DNA replication occurs in various compartments of eukaryotic cells such as the
      nuclei, mitochondria and chloroplasts, the latter of which is used in plants and
      algae. Replication appears to be simpler in the mitochondria than in the nucleus
      where multiple DNA polymerases, which are key enzymes for DNA synthesis, have
      been characterized. In mammals, only one mitochondrial DNA polymerase (pol gamma)
      has been described to date. However, in the mitochondria of the yeast
      Saccharomyces cerevisiae, we have found and characterized a second DNA
      polymerase. To identify this enzyme, several biochemical approaches such as
      proteinase K treatment of sucrose gradient purified mitochondria, analysis of
      mitoplasts, electron microscopy and the use of mitochondrial and cytoplasmic
      markers for immunoblotting demonstrated that this second DNA polymerase is
      neither a nuclear or cytoplasmic contaminant nor a proteolytic product of pol
      gamma. An improved purification procedure and the use of mass spectrometry
      allowed us to identify this enzyme as DNA polymerase alpha. Moreover, tagging DNA
      polymerase alpha with a fluorescent probe demonstrated that this enzyme is
      localized both in the nucleus and in the organelles of intact yeast cells. The
      presence of two replicative DNA polymerases may shed new light on the mtDNA
      replication process in S. cerevisiae.

PMID- 23160076
TI  - [Data for the decrease of "voluntary childlessness" in inflammatory bowel
      disease].
AB  - Inflammatory bowel disease is a chronic disorder affecting young adults in their
      reproductive years, hence its populational consequences are not negligible. While
      fertility in inflammatory bowel disease is the same as in the general population
      (except for male patients with sulphasalazine treatment and females with ileum
      pouch anal anastomosis), "voluntary childlessness" is higher, 14-18%. Patients
      require accurate counseling addressing fertility, pregnancy course and outcome.
      They need to be informed appropriately about risks and benefits of medications in
      inflammatory bowel disease in order to assist their decision making, decrease
      "voluntary childlessness" and improve compliance. Authors review the issues
      related to fertility, outcome of pregnancy, medical treatment options before and
      during pregnancy as well as during breastfeeding in inflammatory bowel disease.

PMID- 23160077
TI  - [5-year experience with varicose vein laser surgery].
AB  - INTRODUCTION: The incidence of varicose veins in the lower limb is relatively
      frequent in Europe including Hungary. AIM: Authors report their 5-year experience
      in varicose vein laser surgery focusing with regards to recurrence and
      complication rates. PATIENTS AND METHODS: Surgery was performed on 647 lower
      limbs in 546 patients with an age between 17 and 80 years. They were overweight
      in 4.6 % of cases. The diameter of treated saphenous veins was between 4 and 31
      mm. Indications for surgery were recurrence in 9.1% of cases and crural ulcer in
      4.0% of cases. Laser fibre was introduced into the varicose saphenous stems and
      then 980 nm, later 1470 nm wavelength laser was delivered while the fibre was
      step-by-step pulled-out. Following the learning period laser energy was raised
      from a mean of 28 J/cm to 164 J/cm because of high recurrence rate. RESULTS:
      During the learning period the recurrence rate was 13.8% while it was 1.9%
      thereafter. Pulmonary embolism occurred in two cases, which could have been
      avoidable. Further minor complications were also noted. CONCLUSIONS: Varicose
      vein laser surgery can be recommended because the recurrence rate is very low,
      major complications can be avoided and minor complications are temporary.

PMID- 23160078
TI  - [The efficiency of influenza vaccines in patients with inflammatory bowel disease
      on immunosuppressive therapy].
AB  - INTRODUCTION: Inactivated influenza vaccination is recommended yearly for
      patients with inflammatory bowel disease on immunosuppressive therapy. AIM: The
      aim of our study was to evaluate the immune response to seasonal influenza
      vaccination in patients with inflammatory bowel disease treated with
      immunosuppressants. PATIENTS AND METHODS: Thirty patients were enrolled in this
      prospective study. Each patient was diagnosed with inflammatory bowel disease and
      treated with immunosuppressants. Blood samples were obtained from patients before
      and one month after influenza vaccination (A/California/7/2009(H1N1),
      A/Perth/16/2009(H3N2) B/Brisbane/60/2008) to assess the pre-and postimmunization
      antibody titers. Virus-specific antibodies were measured by ELISA. RESULTS: The
      vaccine acceptance rate was 53.3%. Local adverse effect occurred in 5 patients.
      Seven patients developed systemic adverse events. Influenza-like symptoms
      occurred in 2 patients, although their antibody titers failed to increase
      significantly. Antibodies to influenza viruses were detected in each patient
      before the vaccination. CONCLUSION: The results confirmed that each patient had
      appropriate antibody titer as correlation of protection even before the
      immunisation. Seroprotection rates were not influenced by the vaccination. The
      vaccine seemed to be safe.

PMID- 23160079
TI  - [Self-perceived health, as an indicator of psychological well-being: behavioural
      epidemiological analysis among the adolescent population].
AB  - BACKGROUND: Self rated health is a widely used measure in behavioural
      epidemiological studies which is a global, informative indicator of health status
      and quality of life. AIM: The main goal of the present study was to examine the
      relationship between subjective health status of adolescents with individual,
      psychological protective and risk factors. METHOD: The authors performed the
      study among youth in Szeged, Hungary in the autumn of 2010. Data collection was
      based on self-administered questionnaires. 656 high school students were included
      in the sample. Logistic regression analyses were applied to detect associations
      including the individual, psychological indicators as dependent variables and
      self perceived health as an independent variable. RESULTS: It was found that
      adolescents with better self perceived health had higher scale points of optimism
      and satisfaction with life, whereas lower self rated health correlated with
      higher values of depression and emotional aggression. There were gender
      differences in both protective and risk factors. Internal locus of control was a
      protective factor while depression, emotional aggression, and external locus of
      control were risk factors of psychological health among girls. CONCLUSION: Self
      rated health can be a possible indicator of subjective well-being that may open a
      way to prevention in behavioural medicine.

PMID- 23160081
TI  - Intracellular nitric oxide delivery from stable NO-polymeric nanoparticle
      carriers.
AB  - The encapsulation of S-nitrosoglutathione into polymeric nanoparticles
      substantially improves NO stability in aqueous media without affecting the
      efficacy of intracellular delivery. The combination of nano-NO delivery and
      chemotherapy has been found to enhance antitumour activity of chemotherapeutics,
      as demonstrated using preliminary in vitro experiments with neuroblastoma cells.

PMID- 23160082
TI  - Cancer mortality in towns in the vicinity of incinerators and installations for
      the recovery or disposal of hazardous waste.
AB  - BACKGROUND: Waste treatment plants release toxic emissions into the environment
      which affect neighboring towns. OBJECTIVES: To investigate whether there might be
      excess cancer mortality in towns situated in the vicinity of Spanish-based
      incinerators and installations for the recovery or disposal of hazardous waste,
      according to the different categories of industrial activity. METHODS: An
      ecologic study was designed to examine municipal mortality due to 33 types of
      cancer, across the period 1997-2006. Population exposure to pollution was
      estimated on the basis of distance from town of residence to pollution source.
      Using Besag-York-Mollie (BYM) regression models with Integrated Nested Laplace
      approximations for Bayesian inference, and Mixed Poisson regression models, we
      assessed the risk of dying from cancer in a 5-kilometer zone around
      installations, analyzed the effect of category of industrial activity, and
      conducted individual analyses within a 50-kilometer radius of each installation.
      RESULTS: Excess cancer mortality (BYM model: relative risk, 95% credible
      interval) was detected in the total population residing in the vicinity of these
      installations as a whole (1.06, 1.04-1.09), and, principally, in the vicinity of
      incinerators (1.09, 1.01-1.18) and scrap metal/end-of-life vehicle handling
      facilities, in particular (1.04, 1.00-1.09). Special mention should be made of
      the results for tumors of the pleura (1.71, 1.34-2.14), stomach (1.18, 1.10
      1.27), liver (1.18, 1.06-1.30), kidney (1.14, 1.04-1.23), ovary (1.14, 1.05
      1.23), lung (1.10, 1.05-1.15), leukemia (1.10, 1.03-1.17), colon-rectum (1.08,
      1.03-1.13) and bladder (1.08, 1.01-1.16) in the vicinity of all such
      installations. CONCLUSIONS: Our results support the hypothesis of a statistically
      significant increase in the risk of dying from cancer in towns near incinerators
      and installations for the recovery or disposal of hazardous waste.

PMID- 23160083
TI  - Integrated health impact assessment of travel behaviour: model exploration and
      application to a fuel price increase.
AB  - Transportation policy measures often aim to change travel behaviour towards more
      efficient transport. While these policy measures do not necessarily target
      health, these could have an indirect health effect. We evaluate the health impact
      of a policy resulting in an increase of car fuel prices by 20% on active travel,
      outdoor air pollution and risk of road traffic injury. An integrated modelling
      chain is proposed to evaluate the health impact of this policy measure. An
      activity-based transport model estimated movements of people, providing
      whereabouts and travelled kilometres. An emission- and dispersion model provided
      air quality levels (elemental carbon) and a road safety model provided the number
      of fatal and non-fatal traffic victims. We used kilometres travelled while
      walking or cycling to estimate the time in active travel. Differences in health
      effects between the current and fuel price scenario were expressed in Disability
      Adjusted Life Years (DALY). A 20% fuel price increase leads to an overall gain of
      1650 (1010-2330) DALY. Prevented deaths lead to a total of 1450 (890-2040) Years
      Life Gained (YLG), with better air quality accounting for 530 (180-880) YLG,
      fewer road traffic injuries for 750 (590-910) YLG and active travel for 170 (120
      250) YLG. Concerning morbidity, mostly road safety led to 200 (120-290) fewer
      Years Lived with Disability (YLD), while air quality improvement only had a minor
      effect on cardiovascular hospital admissions. Air quality improvement and
      increased active travel mainly had an impact at older age, while traffic safety
      mainly affected younger and middle-aged people. This modelling approach
      illustrates the feasibility of a comprehensive health impact assessment of
      changes in travel behaviour. Our results suggest that more is needed than a
      policy rising car fuel prices by 20% to achieve substantial health gains. While
      the activity-based model gives an answer on what the effect of a proposed policy
      is, the focus on health may make policy integration more tangible. The model can
      therefore add to identifying win-win situations for both transport and health.

PMID- 23160084
TI  - Isolation and characterization of Aschersonia placenta from citrus orchards and
      its pathogenicity towards Dialeurodes citri (Ashmead).
AB  - For selecting potential biological agents to control Dialeurodes citri, a major
      insect pest in China's citrus orchards, 75 native Aschersonia isolates were
      selected from infected whiteflies in citrus orchards and were evaluated for
      virulence to third instar nymphs of D. citri at a concentration of 1 *
      10(6)conidia/ml. The mortality rates of D. citri varied from 0% to 72.70%. Among
      the 75 Aschersonia isolates, three (HB10, HB12 and ZJ9) were the most virulent
      and pathogenic to D. citri and caused more than 69% mortality. The 50% lethal
      concentration (LC(50)) values of them were 1.86 * 10(6), 3.40 * 10(6) and 6.81 *
      10(6)conidia/ml, respectively. The three isolates also produced conidia
      abundantly on potato dextrose agar medium (3.95 * 10(6), 6.19 * 10(6) and 7.34 *
      10(6)conidia/cm(2), respectively). They were identified to be Aschersonia
      placenta based on their morphological analysis. Phylogenetic analysis showed that
      these three highly virulent Aschersonia isolates belong to a strongly supported
      clade that includes two other A. placenta isolates obtained from Vietnam and
      Thailand. In summary, these results indicate the possibility of developing the
      three most virulent A. placenta isolates as microbiological control agents
      against citrus whitefly.

PMID- 23160085
TI  - Distribution and diversity analysis of Bacillus thuringiensis cry genes in
      different soil types and geographical regions of India.
AB  - Molecular characterization of 117 Bacillus thuringiensis (Bt) isolates from
      various geographical locations was previously done by PCR amplification of cry
      genes. In present investigation, diversity of cry genes from different soil types
      and climatic environments was studied using rarefaction method. Presence of cry1,
      cry2, cry3, 7, 8, cry4, cry5, 12, 14, 21, cry11, cry13 and cyt1 genes from Bt
      strains isolated from various regions of India was determined by PCR
      amplification. A varied distribution of cry genes and their profiles was found in
      four soil types. The cry1 gene was the most abundant in the isolates from four
      soil types and geographical regions. A higher degree of cry gene diversity was
      observed in isolates from alluvial soil. Rarefaction analysis indicated that more
      cry genes could be found from various soil types. Distribution of cry genes in
      semi arid, subtropical humid and tropical dry regions was varied but the degree
      of cry gene diversity determined by rarefaction analysis was similar. No major
      difference in distribution and diversity of cry genes was found in agricultural
      and non-agricultural samples except the absence of cry3 and cry13 genes in
      isolates of non-agricultural samples. We report the utility of rarefaction
      analysis to compare cry gene diversity from different geographical regions.

PMID- 23160086
TI  - Mental disorders in somatic diseases: psychopathology and treatment.
AB  - The prevalence of various mental disorders (especially anxiety syndromes,
      personality disorders, and addictions--somatoform, conversion and dissociative,
      dysthymic and depressive) during the life span reaches even up to 30% in the
      general population. It is significantly higher among people suffering from
      various diseases due to a variety of complex reasons, such as acute or chronic
      reaction to severe illness, suboptimal adaptation to hospitalization or
      disability, side effects of pharmacotherapy, and hormonal or metabolic changes.
      In all likelihood, physicians of all specialties have at least a few patients
      with mental disorders, which are either independent of or are secondary to a
      treated disease. These disorders may often substantially decrease the quality of
      life and the progress of treatment and rehabilitation.

PMID- 23160087
TI  - Luminescent N,O-chelated chroman-BF2 complexes: structural variants of BODIPY.
AB  - The synthesis and characterization of 5-(chromen-4-one)-dipyrromethane (1), 5-(6
      methyl-chromen-4-one)-dipyrromethane (2), 5-(6-isopropyl-chromen-4-one)
      dipyrromethane (3) and the respective chromans, 7-[2-pyrrolo]-pyrrole[1,2-a]12H
      pyrrolino[2,3-b]chroman-4-one (4), 4-methyl-7-[2-pyrrolo]-pyrrole[1,2-a]12H
      pyrrolino[2,3-b]-chroman-4-one (5) and 4-isopropyl-7-[2-pyrrolo]-pyrrole[1,2
      a]12H pyrrolino[2,3-b]-chroman-4-one (6) have been described. Chroman derivatives
      4-6 have been used in the synthesis of highly stable, fluorescent,
      borondifluoride complexes (7-9). All the compounds have been fully characterised
      by various physicochemical techniques viz., elemental analyses, IR, HRMS, NMR
      ((1)H, (13)C), electronic absorption, emission (solution and solid state),
      electrochemical and thermal studies. Crystal structures of dipyrromethanes 1 and
      2, chroman derivative 6 and boron complexes 7-9 have been determined by X-ray
      single crystal analyses. Structural studies revealed that the formation of 4-6
      takes place by DDQ mediated C-N coupling. The higher stability of 4-6 relative to
      their respective dipyrrins has been supported by theoretical studies.

PMID- 23160088
TI  - Synthesis and antimicrobial evaluation of pogostone and its analogues.
AB  - Pogostone (PO) is one of the secondary metabolites from Pogostemon cablin
      (Blanco) Benth. (Lamiaceae), serving as the effective component of the
      antimicrobial activity. In this study, PO and a series of its analogues were
      synthesized by the reaction of dehydroacetate and aldehydes in tetrahydrofuran
      under a nitrogen atmosphere. Their activities against Candida albicans, Gram
      positive bacteria and Gram negative bacteria were evaluated. The antifungal
      results demonstrated that PO (MIC ranged from 12 to 97MUg/mL against all strains,
      MFC ranged from 49 to 97MUg/mL against all strains) and A3 (MIC ranged from 12 to
      49, MFC over 195MUg/mL) showed a strong activity against Candida albicans. While
      A1 (MIC ranged from 49 to 97MUg/mL) and A2 (MIC ranged from 24 to 49MUg/mL) have
      only shown effect against Guangzhou clinical isolates, the antibacterial results
      demonstrated that PO and its analogues showed no effects against the tested
      bacteria strains. This study suggests that pogostone analogues, with the
      appropriated structure modification, represented a kind of promising antifungal
      agents.

PMID- 23160089
TI  - Two new chromone glycosides from Drynaria fortunei.
AB  - Two new chromone glycosides, drynachromoside A (1), drynachromoside B (2), along
      with three known flavanones, 5,7,3',5'-tetrahydroxy-flavanone (3), 5,7,3',5'
      tetrahydroxy-flavanone-7-O-beta-d-glucopyranoside (4), and 5,7,3',5'-tetrahydroxy
      flavanone-7-O-neohesperidoside (5), were isolated from the dry rhizomes of
      Drynaria fortunei by means of bio-active screening. The two former compounds were
      elucidated on the basis of physico-chemical property and spectroscopic data. The
      osteoblastic proliferation activities of these flavonoids were evaluated by the
      method of MTT. The results showed that compound 1 exhibited the biochemical
      effects on the proliferation of MC3T3-E1 cells, while Compound 2 showed
      inhibitory effects against MC3T3-E1 cells.

PMID- 23160090
TI  - Hydroxysafflor yellow a inhibits lipopolysaccharide-induced inflammatory signal
      transduction in human alveolar epithelial A549 cells.
AB  - Hydroxysafflor yellow A (HSYA) is an active ingredient obtained from the flower
      of Carthamus tinctorius L. The present study investigated the effects of HSYA on
      lipopolysaccharide (LPS)-induced inflammatory signal transduction in human
      alveolar epithelial A549 cells. A549 cells stimulated with LPS were incubated
      with three doses of HSYA (1, 4 and 16MUmol/L). HSYA suppressed the expression of
      TLR-4, Myd88, ICAM-1, TNFalpha, IL-1beta and IL-6 at the mRNA and protein level,
      and inhibited the adhesion of leukocytes to A549 cells. HSYA treatment also
      decreased NF-kappaB p65 nuclear translocation and inhibited the phosphorylation
      of p38 mitogen-activated protein kinase (p38 MAPK). These findings suggest that
      HSYA effectively inhibits LPS-induced inflammatory signal transduction in A549
      cells.

PMID- 23160091
TI  - Platelet-activating factor (PAF)-antagonists of natural origin.
AB  - Presently herbal medicines are being used by about 80% of the world population
      for primary health care as they stood the test of time for their safety,
      efficacy, cultural acceptability and lesser side effects. The discovery of
      platelet activating factor antagonists (PAF antagonists) during these decades are
      going on with different framework, but the researchers led their efficiency in
      studying in vitro test models. Since it is assumed that PAF play a central role
      in etiology of many diseases in humans such as asthma, neuronal damage, migraine,
      cardiac diseases, inflammatory, headache etc. Present days instinctively
      occurring PAF antagonist exists as a specific grade of therapeutic agents for the
      humans against these and different diseases either laid hold of immunological or
      non-immunological types. Ginkgolide, cedrol and many other natural PAF
      antagonists such as andrographolide, alpha-bulnesene, cinchonine, piperine,
      kadsurenone, different Piper species' natural products and marine origin plants
      extracts or even crude drugs having PAF antagonist properties are being used
      currently against different inflammatory pathologies. This review is an attempt
      to summarize the data on PAF and action of natural PAF antagonists on it, which
      were evaluated by in vivo and in vitro assays.

PMID- 23160092
TI  - Effects of the extracts and an active compound curcumenone isolated from Curcuma
      zedoaria rhizomes on alcohol-induced drunkenness in mice.
AB  - The Curcuma zedoaria rhizome has been used traditionally to treat
      gastrointestinal diseases as an aromatic stomachic drug, and this is currently
      used to treat alcohol-induced loss of appetite and nausea in Japan. We examined
      the effects of various fractions and isolated compounds on alcohol-induced
      drunkenness and blood alcohol concentrations in mice. The 30% ethanol-extract
      (1000mg/kg) of C. zedoaria rhizome prevented drunkenness 60 and 120min after 40%
      alcohol administration. The n-hexane-soluble fraction (300mg/kg) and an isolated
      compound (3, 10 or 30mg/kg) prevented drunkenness at 30, 60 or 120min. The
      extract, n-hexane-soluble fraction and isolated compound reduced the elevation in
      blood alcohol concentrations 30 and 60min after 40% alcohol administration. The
      isolated compound (10 and 30mg/kg) enhanced liver ADH activity 30 and 60min after
      40% alcohol administration. The compound was identified as curcumenone by a
      direct comparison of (1)H- and (13)C-NMR spectral data. In conclusion, the
      protective effect of the C. zedoaria extract on drunkenness might be due to an
      active substance, curcumenone, and decreases in the elevation of blood alcohol
      concentrations through increased liver alcohol dehydrogenase activity.

PMID- 23160094
TI  - Temperature dependence of the electrical resistivity and electronic structure of
      amorphous Fe100-xZrx films and multilayers.
AB  - The electrical resistivity of amorphous Fe(100-x)Zr(x) metal alloy films and
      multilayers has been investigated in a wide temperature and composition range.
      The overall behavior of the resistivity is consistent with bulk measurements,
      exhibiting prominent semiconductor-like changes at low temperatures. The
      transition from positive (metallic) to negative temperature coefficient of
      resistivity behavior is accompanied by minute changes in magnetoresistance and we
      can therefore rule out magnetic phase changes as being the cause for the observed
      changes in the resistivity. Using x-ray absorption and emission spectroscopies we
      are able to probe the unoccupied and occupied electronic densities of states. The
      corresponding spectra are found to significantly overlap, as expected for a
      metallic-like electronic structure and the absence of a band gap. Besides a
      broadening of the x-ray emission lines expected from an amorphous material,
      remarkably small differences are observed in the electronic structures when
      changing the amount of Zr. The resistivity data were modeled and agreement with
      the Mott variable range hopping model was found, indicating localized electronic
      states due the disordered structure of the Fe(100-x)Zr(x) alloys.

PMID- 23160095
TI  - Conversation analysis in the differential diagnosis of Italian patients with
      epileptic or psychogenic non-epileptic seizures: a blind prospective study.
AB  - The differential diagnosis of epileptic seizures (ES) and psychogenic non
      epileptic seizures (PNES) is often difficult. The diagnostic gold standard is
      video-EEG, but this procedure is limited because of its high cost and is not
      always available. Research groups from Germany and Britain have used conversation
      analysis (CA) of patients' descriptions of their seizures as a means of
      differentiating the type of seizure. The aim of this study was to verify the
      value of their considerations in relation to the Italian language. Ten subjects
      (five with ES and five with PNES) diagnosed by means of the video-EEG recording
      of one seizure were studied under blind conditions by a linguist. The patients
      with ES described their seizures in as much detail as possible and tried to
      reconstruct the experience as fully as they can, making an effort to describe
      their subjective symptoms, quantify the duration of the phases preceding and
      following the seizure, and use the image of an external entity overcoming them.
      On the contrary, the patients with PNES repeated their extraneousness to the
      events that occur, refused to reply, expressed amnesia, reconstructed the
      happening by referring to descriptions provided by witnesses, and often describe
      their seizures using the image of an internal entity of which they were victims.
      The linguist correctly identified nine cases out of ten using CA.

PMID- 23160093
TI  - A cytokine axis regulates elastin formation and degradation.
AB  - Underlying the dynamic regulation of tropoelastin expression and elastin
      formation in development and disease are transcriptional and post-transcriptional
      mechanisms that have been the focus of much research. Of particular importance is
      the cytokine-governed elastin regulatory axis in which the pro-elastogenic
      activities of transforming growth factor beta-1 (TGFbeta1) and insulin-like
      growth factor-I (IGF-I) are opposed by anti-elastogenic activities of basic
      fibroblast growth factor (bFGF/FGF-2), heparin-binding epidermal growth factor
      like growth factor (HB-EGF), EGF, PDGF-BB, TGFalpha, tumor necrosis factor-alpha
      (TNF-alpha), interleukin (IL)-1beta and noncanonical TGFbeta1 signaling. A key
      mechanistic feature of the regulatory axis is that cytokines influence elastin
      formation through effects on the cell cycle involving control of cyclin-cyclin
      dependent kinase complexes and activation of the Ras/MEK/ERK signaling pathway.
      In this article we provide an overview of the major cytokines/growth factors that
      modulate elastogenesis and describe the underlying molecular mechanisms for their
      action on elastin production.

PMID- 23160096
TI  - Proceedings of the Third International Workshop on Advances in
      Electrocorticography.
AB  - The Third International Workshop on Advances in Electrocorticography (ECoG) was
      convened in Washington, DC, on November 10-11, 2011. As in prior meetings, a true
      multidisciplinary fusion of clinicians, scientists, and engineers from many
      disciplines gathered to summarize contemporary experiences in brain surface
      recordings. The proceedings of this meeting serve as evidence of a very robust
      and transformative field but will yet again require revision to incorporate the
      advances that the following year will surely bring.

PMID- 23160097
TI  - The reasons for the epilepsy treatment gap in Kilifi, Kenya: using formative
      research to identify interventions to improve adherence to antiepileptic drugs.
AB  - Many people with epilepsy (PWE) in resource-poor countries do not receive
      appropriate treatment, a phenomenon referred to as the epilepsy treatment gap
      (ETG). We conducted a qualitative study to explore the reasons for this gap and
      to identify possible interventions in Kilifi, Kenya. Focus group discussions
      (FGDs) were carried out of PWE and their caregivers. Individual interviews were
      conducted of PWE, their caregivers, traditional healers, community health workers
      and leaders, nurses and doctors. In addition, a series of workshops was
      conducted, and four factors contributing to the ETG were identified: 1) lack of
      knowledge about the causes, treatment and prognosis of epilepsy; 2)
      inaccessibility to antiepileptic drugs; 3) misconceptions about epilepsy derived
      from superstitions about its origin; 4) and dissatisfaction with the
      communication skills of health providers. These data indicated possible
      interventions: 1) education and support for PWE and their caregivers; 2)
      communication skills training for health providers; 3) and improved drug
      provision.

PMID- 23160098
TI  - Natural variation in a homolog of Antirrhinum CENTRORADIALIS contributed to
      spring growth habit and environmental adaptation in cultivated barley.
AB  - As early farming spread from the Fertile Crescent in the Near East around 10,000
      years before the present, domesticated crops encountered considerable ecological
      and environmental change. Spring-sown crops that flowered without the need for an
      extended period of cold to promote flowering and day length-insensitive crops
      able to exploit the longer, cooler days of higher latitudes emerged and became
      established. To investigate the genetic consequences of adaptation to these new
      environments, we identified signatures of divergent selection in the highly
      differentiated modern-day spring and winter barleys. In one genetically divergent
      region, we identify a natural variant of the barley homolog of Antirrhinum
      CENTRORADIALIS (HvCEN) as a contributor to successful environmental adaptation.
      The distribution of HvCEN alleles in a large collection of wild and landrace
      accessions indicates that this involved selection and enrichment of preexisting
      genetic variants rather than the acquisition of mutations after domestication.

PMID- 23160100
TI  - Should perioperative supplemental oxygen be routinely recommended for surgery
      patients? A Bayesian meta-analysis.
AB  - OBJECTIVE: The purpose of this study is to use updated data and Bayesian methods
      to evaluate the effectiveness of hyperoxia to reduce surgical site infections
      (SSIs) and/or mortality in both colorectal and all surgery patients. Because few
      trials assessed potential harms of hyperoxia, hazards were not included.
      BACKGROUND: Use of hyperoxia to reduce SSIs is controversial. Three recent meta
      analyses have had conflicting conclusions. METHODS: A systematic literature
      search and review were performed. Traditional fixed-effect and random-effect meta
      analyses and Bayesian meta-analysis were performed to evaluate SSIs and
      mortality. RESULTS: Traditional meta-analysis yielded a relative risk of an SSI
      with hyperoxia among all surgery patients of 0.84 [95% confidence interval (CI):
      0.73-0.97] and 0.84 (95% CI: 0.61-1.16) for the fixed-effect and random-effect
      models, respectively. The probabilities of any risk reduction in SSIs among all
      surgery patients were 77%, 81%, and 83% for skeptical, neutral, and enthusiastic
      priors. The subset analysis of colorectal surgery patients increased the
      probabilities to 86%, 89%, and 92%. The probabilities of at least a 10% reduction
      were 57%, 62%, and 68% for all surgery patients and 71%, 75%, and 80% among the
      colorectal surgery subset. CONCLUSIONS: There is a moderately high probability of
      a benefit to hyperoxia in reducing SSIs in colorectal surgery patients; however,
      the magnitude of benefit is relatively small and might not exceed treatment
      hazards. Further studies should focus on generalizability to other patient
      populations or on treatment hazards and other outcomes.

PMID- 23160102
TI  - Coagulation and the vessel wall in thrombosis and atherosclerosis.
AB  - The blood coagulation system is a key survival mechanism that has developed to
      protect man against lethal bleeding. A second function of blood coagulation is
      its close interaction with immunity. The immune-mediated coagulation responses
      may broadly be regarded as an element of response to injury. Pathological
      coagulation responses, including thromboembolism and disseminated intravascular
      coagulation (DIC), could therefore be regarded as excessive immune responses to a
      vessel wall injury. Virchow's triad, which comprises changes in the components of
      the blood, the state of the vessel wall, and the blood flow, was originally
      proposed for venous thrombosis. However, lately it appears that the same
      principles can be applied to arterial thrombosis and even DIC. It has even been
      postulated that all forms of thrombosis may be part of a continuous spectrum of
      the same disease. Over the past few years, an accumulation of evidence has shown
      that the etiopathogenetic mechanisms behind venous and arterial thrombosis are
      quite similar. The traditional elements of Virchow's triad are found to apply to
      both arterial and venous thrombosis. Yet, nowadays more emphasis is placed on the
      vessel wall and vascular bed specificity and the interaction with inflammation
      and hypercoagulability. This narrative review will discuss recent advances in
      research on the possible interactions between coagulation, the vascular
      endothelium, and atherosclerosis as well as the consequences of such interactions
      for venous and arterial thrombosis.

PMID- 23160099
TI  - A genome-wide association study identifies susceptibility loci for nonsyndromic
      sagittal craniosynostosis near BMP2 and within BBS9.
AB  - Sagittal craniosynostosis is the most common form of craniosynostosis, affecting
      approximately one in 5,000 newborns. We conducted, to our knowledge, the first
      genome-wide association study for nonsyndromic sagittal craniosynostosis (sNSC)
      using 130 non-Hispanic case-parent trios of European ancestry (NHW). We found
      robust associations in a 120-kb region downstream of BMP2 flanked by rs1884302 (P
      = 1.13 * 10(-14), odds ratio (OR) = 4.58) and rs6140226 (P = 3.40 * 10(-11), OR =
      0.24) and within a 167-kb region of BBS9 between rs10262453 (P = 1.61 * 10(-10),
      OR = 0.19) and rs17724206 (P = 1.50 * 10(-8), OR = 0.22). We replicated the
      associations to both loci (rs1884302, P = 4.39 * 10(-31) and rs10262453, P = 3.50
      * 10(-14)) in an independent NHW population of 172 unrelated probands with sNSC
      and 548 controls. Both BMP2 and BBS9 are genes with roles in skeletal development
      that warrant functional studies to further understand the etiology of sNSC.

PMID- 23160103
TI  - How should debriefing be undertaken in web-based studies? Findings from a
      randomized controlled trial.
AB  - BACKGROUND: Internet research may raise older ethical issues in new forms or pose
      new issues. It has been recommended that debriefing information online be kept
      very short, with further information including study results made available if
      requested by participants. There are no empirical studies that compare possible
      alternative methods of debriefing in online studies. OBJECTIVE: To undertake a
      randomized controlled trial evaluating how to implement the recommended approach
      by assessing the effects of two different approaches on accessing of additional
      information. METHODS: All 11,943 participants in the Effects of Study Design and
      Allocation (ESDA) study, which employed deception, were randomly assigned to one
      of two methods of debriefing: Group A  received the debriefing information in the
      body of an email with links to protocol and results pages; Group B was presented
      with these links after clicking on an initial link in the body of the email to
      view the debriefing information on a website. Outcomes assessed were the
      proportions clicking on the links to the protocol and results summary and the
      time spent on these pages by those accessing them. RESULTS: The group who were
      presented with no debriefing information in the body of the email and went to a
      website for this information (Group B) were approximately twice as likely to
      subsequently access the protocol and the results summary. These differences
      between the two groups were highly statistically significant. Although these
      differences are clear, the overall proportions accessing such information were
      low, and there were no differences in mean time spent reading these pages. Only
      one quarter of Group B actually accessed debriefing information. CONCLUSIONS: In
      circumstances where the uptake of fuller information on study design, methods,
      and findings is deemed important, debriefing information may be better provided
      via a link and not included in the body of an email. Doing so may, however,
      reduce the extent of receiving any debriefing information at all. There is a
      wider need for high quality empirical studies to inform ethical evaluations.
      TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry,
      ACTRN12610000846022 (http://www.anzctr.org.au/).

PMID- 23160104
TI  - EZ-IO((r)) intraosseous device implementation in a pre-hospital emergency
      service: A prospective study and review of the literature.
AB  - INTRODUCTION: Intraosseous access is increasingly recognised as an effective
      alternative vascular access to peripheral venous access. We aimed to
      prospectively study the patients receiving prehospital intraosseous access with
      the EZ-IO((r)), and to compare our results with those of the available
      literature. METHODS: Every patient who required an intraosseous access with the
      EZ-IO from January 1st, 2009 to December 31st, 2011 was included. The main data
      collected were: age, sex, indication for intraosseous access, localisation of
      insertion, success rate, drugs and fluids administered, and complications. All
      published studies concerning the EZ-IO device were systematically searched and
      reviewed for comparison. RESULTS: Fifty-eight patients representing 60 EZ-IO
      procedures were included. Mean age was 47 years (range 0.5-91), and the success
      rate was 90%. The main indications were cardiorespiratory arrest (74%), major
      trauma (12%), and shock (5%). The anterior tibia was the main route. The main
      drugs administered were adrenaline (epinephrine), atropine and amiodarone. No
      complications were reported. We identified 30 heterogeneous studies representing
      1603 EZ-IO insertions. The patients' characteristics and success rate were
      similar to our study. Complications were reported in 13 cases (1.3%). CONCLUSION:
      The EZ-IO provides an effective way to achieve vascular access in the pre
      hospital setting. Our results were similar to the cumulative results of all
      studies involving the use of the EZ-IO, and that can be used for comparison for
      further studies.

PMID- 23160105
TI  - Cardiovascular events increased at normal and high-normal blood pressure in young
      and middle-aged Japanese male smokers but not in nonsmokers.
AB  - OBJECTIVE: To clarify whether the impact of normal and high-normal BP (BP) per se
      on cardiovascular disease (CVD) and all-cause death differs depending on smoking
      status. METHODS AND RESULTS: A prospective observational cohort study (median
      follow-up period: 7.5 years) was performed among 25,077 healthy nondiabetic
      Japanese men aged 20-61 years (mean age 37.3 years), whose BP was less than
      150/95 mmHg and who were not on medication. Hazard ratios (HRs), adjusted by
      known risk factors and a change in annual BP during the follow-up, were
      calculated by the Cox proportional model with less than 119/75 mmHg as a
      reference. Among smokers, CVD events increased significantly from a SBP of 120
      mmHg, with HRs of 2.68 (120-129 mmHg), 4.28 (130-139 mmHg), and 11.7 (140-149
      mmHg). The CVD events also increased from a DBP of 75 mmHg (P for trend less than
      0.0001), with 75-79 mmHg and 90-94 mmHg considered statistically significant.
      Among noncurrent smokers, 110-149 mmHg (SBP) and 75-89 mmHg (DBP) were not
      associated with elevated HRs for CVD. The relation between BP and all-cause
      mortality was similar among both current and noncurrent smokers: 140-149 mmHg
      (SBP) and 90-94 mmHg (DBP) were significantly associated with elevated risk, and
      130-139 mmHg (SBP) among noncurrent smokers associated with elevated risk.
      CONCLUSION: Young and middle-aged healthy Japanese individuals with normal and
      high-normal BP (120-139/75-89 mmHg) were at risk for CVD among smokers, even
      after adjusting for an annual change in BP.

PMID- 23160106
TI  - [Adult ADHD: clinical aspects and therapeutic implications].
AB  - Attention Deficit Hyperactivity Disorder (ADHD) has been originally described as
      a disorder of childhood and adolescence. In the last years, a huge amount of
      evidence supports a syndromal continuity form childhood to adulthood. the
      identification of ADHD in adults raises several problems of differential
      diagnosis and the disorder is frequently associated with other mental disorders,
      at least in patients referred to psychiatric settings. It is not clear if adult
      ADHD is characterized by a specific pattern of symptoms that include attentive
      deficits and consequent behavioral manifestations, instead of hyperactivity.
      Comorbidity with other mental disorders influences clinical picture, severity,
      course and treatment outcome. In particular comorbid ADHD, bipolar disorder and
      alcohol/substance abuse disorders coexist in a relevant proportion of cases and
      it might represent a specific phenoptype, associated with treatment resistance.
      Substances use, often poly-drug abuse, such as alcohol, cocaine, stimulants and
      heroin, inevitably complicates course and therapeutic choice. The recognition of
      ADHD in adults has important implications at therapeutic level, even when present
      as incomplete and residual forms. Psychostimulants and other compounds with
      specific efficacy on ADHD symptomatology has been shown to be useful also in
      adults both in monotherapy and in association with other drugs, such as mood
      stabilizers. However their use should be cautious when a mood disorder coexists,
      for the possible induction of manic-switches or rapid cycling. Further research
      is necessary in order to better characterize the clinical picture of ADHD in
      adults and to elaborate widely shared treatment guidelines.

PMID- 23160107
TI  - [Neurological soft signs: meaning and relevance along the course of psychiatric
      illness. An objective and rapid screening for psychosis?].
AB  - AIMS: Neurological soft signs (NSS) are minor neurological anomalies indicating
      non-specific cerebral dysfunction, commonly assessed through the Neurological
      Evaluation Scale (NES). It is generally accepted that NSS are prevalent in
      schizophrenic patients respect to healthy subjects, but they have been also found
      in patients with other neurological and psychiatric disorders. We sought to
      review studies that have specifically investigated NSS in schizophrenia, bipolar
      disorder and obsessive-compulsive disorder, and we also focused on their
      relationship with psychopathological features and antipsychotic treatment.
      METHODS: In this review we selected published studies investigating NSS in
      psychiatric patients and their relationship with either psychopathological
      features and antipsychotic treatment. RESULTS: Apart from diagnosis, all patients
      show more NSS than healthy subjects, but schizophrenic patients perform worse
      respect to other psychiatric diseases. These signs are already present at the
      onset of the disease. NSS also show a significant correlation with
      psychopathological measures and they can be predictive of clinical course and
      response to medications. On the other hand, NSS can be independent of the
      pharmacological treatment. CONCLUSIONS: These findings argued the hypothesis that
      NSS could be a trait characteristic in psychosis. NSS are an objective measure
      for the assessment of serious psychiatric disorder in the prodromal phase, at
      onset and along the course of the disease.

PMID- 23160108
TI  - Duloxetine in the treatment of elderly people with major depressive disorder.
AB  - INTRODUCTION: The elderly population is more frequently subjected to depressive
      mood compared to the general population and show peculiarities affecting
      responsiveness; furthermore, aged people need also special care. Duloxetine is a
      relatively new antidepressant that proved to be effective in adult depression,
      but has received little attention in elderly population heretofore. AIM: To
      review the evidence of duloxetine in late-life major depressive disorder (MDD).
      METHOD: A systematic review of studies focusing on the use of duloxetine in MDD
      in the elderly has been carried out through the principal specialized databases,
      including PubMed, PsycLIT, and Embase. RESULTS: Only a handful of papers were
      specifically dedicated to this issue. Duloxetine was found to be effective and
      safe in old-age MDD, to be better than placebo on many clinical measures in all
      studies, and to better differentiate from placebo with respect to selective
      serotonin reuptake inhibitors. Compared to placebo, its side-effect profile is
      slightly unfavorable and its drop-out rate is slightly higher. Furthermore, when
      pain is present in old-age MDD, duloxetine is able to reduce it. CONCLUSIONS: The
      efficacy and safety of duloxetine in old-age depression are similar to those
      encountered in adult MDD. There is a relative lack of comparative studies other
      than with placebo. The special needs of elderly patients with MDD must be
      addressed with close patient contact to avoid the perils of inappropriate dosing.

PMID- 23160109
TI  - Early onset of action and sleep-improving effect are crucial in decreasing
      suicide risk: the role of quetiapine XR in the treatment of unipolar and bipolar
      depression.
AB  - Although the possibilities of antidepressive pharmacotherapy are continuously
      improving, the rate of nonresponders or partial responders is still relatively
      high. Suicidal behavior, the most tragic consequence of untreated or
      unsuccessfully treated depression, commonly observed in the first few weeks of
      antidepressive treatment before the onset of therapeutic action, is strongly
      related to certain symptoms of depression like insomnia. The present paper
      reviews the newly discovered and well-documented antidepressive effect of
      quetiapine in bipolar and unipolar depression with special focus on its early
      onset of action and its sleep-improving effects. Both beneficial effects play an
      important role in the reduction of suicidal risk frequently observed in depressed
      patients.

PMID- 23160110
TI  - [Internet addiction disorder and social networks: statistical analysis of
      correlation and study of the association with social interaction anxiousness].
AB  - INTRODUCTION: Internet Addiction Disorder (IAD) is an emerging psychiatric
      disorder, assimilable to impulse control problems and related to maladaptive use
      of new networks and social and virtual technologies. AIM: Our study aims to
      analyze the presence of IAD among adolescents and to study the correlation with
      social interaction anxiousness. We investigated also the possibility that the
      Social Network (SN) represent a source of risk for the development of IAD.
      MATERIALS AND METHODS: The test group was composed of 250 subjects, aged between
      14 and 18 years. They were administered: Young's IAT; IAS (Interaction
      Anxiousness Scale), AAS (Audience Anxiousness Scale) and SISST (Social
      Interaction Self-Statement Test) to analyze the dimension of social interaction
      anxiousness. RESULTS: We found a rate of 2% of the IAD. The SN are the most
      common use of the Net in our sample, but not the most clicked sites by subjects
      with IAD. It should be noted, finally, a correlation between social interaction
      anxiety and IAD, but not a significant difference in scores of social anxiousness
      scales based on the SN use/non-use. CONCLUSIONS: The use of SN intended as single
      variable doesn't correlate with increased risk for IAD, or for increased social
      interaction anxiousness. However, if associated with prolonged use of the net for
      5-6 hours or more, or concomitant use of chat rooms and/or net gambling, we find
      a more significant risk of psychopathology. The data presented require further
      investigations, in order to guide new pathogenetic models and appropriate
      intervention strategies.

PMID- 23160111
TI  - [Motivation in brief psychotherapy: a 30 patients study, valued in a psychiatric
      day-hospital].
AB  - INTRODUCTION: The most important predictive factor for a successful outcome in
      Brief Psychotherapy is the motivation of patients to the treatment itself.
      Against the scarcity of literature on the subject, so far limited to offer
      standardized tools to assess motivation, applied mainly to education and work's
      areas, in spite of a possible application in psychotherapy, it was considered
      necessary to develop a questionnaire ad hoc. MATERIALS AND METHODS: It was
      therefore created a pattern of motivational diagnosis of the problem based on a
      sequence of questions and answers, which would make possible the classification
      of each case and then that could lead to the use of a specific method. It is the
      result of the attempt to create an orderly pattern and that it would be easy to
      use and then be analyzed. The questionnaire consists of twenty one questions and
      requires that the patient answers with a "yes" or a "no" to each applicant. It
      was administered to thirty patients who came from the psychiatric day hospital.
      The questionnaire was used as a "not standardized thread" in which, through
      groups of questions, are addressed some central cores: the spontaneous activity,
      motivation controlled from the outside, motivation directed to an activity that
      leads to results, motivation to and activity for a purpose, expectations of self
      efficacy, the presence/absence of resistance and finally the area of the will.
      The purpose of this work is to show, bringing a contribution in agreement with
      the few studies on the subject, how motivation is a key parameter for predicting
      the effectiveness of a psychotherapy, in this case, Brief Psychotherapy.
      CONCLUSIONS: The study clearly shows how the motivation is the most important
      positive predictor in the preliminary assessment of a Brief Psychotherapy:
      results in treatment are most likely to be rapid and favorable if patients are
      motivated to change andif they are engaged with the therapist.

PMID- 23160112
TI  - [Long-term treatment of bipolar disorder: how should we use lithium salts?].
AB  - Despite the great quantity of evidence supporting the efficacy of lithium in the
      maintenance treatment of bipolar disorder (BD), its use has often been limited
      because of issues about the management of this compound. W aimed to evaluate the
      use of lithium in common clinical practice and to identify possible relationships
      between the trend over time of serum lithium levels and clinical course of the
      illness. METHODS: 98 patients with bipolar I and bipolar II disorder (DSM-IV-TR)
      on maintenance treatment with lithium salts were recruited and followed up in a
      naturalistic trial at the Day Hospital of Psychiatric Clinic of Pisa. Diagnosis
      was confirmed using a structured interview, the SCID-I. During symptom
      assessment, the Clinical Global Impression-Bipolar Version Scale (CGI-BP) was
      used. RESULTS: The sample is made up mainly of BI patients (87.8%) and lithium is
      used in association with anticonvulsants in 63%. Less than half of the sample
      (48%) presents average serum lithium levels in the therapeutic range (0.5-0.8
      mEq/L); serum values of lithium within the range were seen more frequently in
      patients with manic/mixed episode, with manic/mixed polarity of onset, with a
      greater number of previous episodes, with a higher percentage of rapid cycling
      and in subjects treated with lithium associated with anticonvulsants. During the
      follow-up patients with average serum lithium levels within the therapeutic range
      obtained a clinical improvement in a significantly greater proportion compared to
      patients with average serum lithium levels lower than 0.50 mEq/L. DISCUSSION: In
      clinical practice, lithium is often used at doses determining serum levels at the
      lower limits of the therapeutic range. Preliminary data on the prospective course
      of the illness support the importance of maintaining serum values of lithium
      within the therapeutic range.

PMID- 23160113
TI  - Daily serum and salivary BDNF levels correlate with morning-evening personality
      type in women and are affected by light therapy.
AB  - INTRODUCTION: BDNF is present in human serum and its level changes have been used
      as a marker of antidepressant efficacy in some psychiatric disorders. In
      addition, the positive effects of light therapy on major depression suggest that
      circadian-regulated factors should be taken into account in the management of
      mood disorders. The aim of the present study was to test ultradian fluctuations
      in serum and salivary BDNF levels and their interaction with light therapy in a
      sample of healthy women. METHODS: The study included 16 young women.
      Psychopathological status and chronotype traits were assessed by SPAQ, BDI, STAI,
      TAS, and MEQ. Standard light treatment protocol was applied. Serum and saliva
      were collected at 8.00, 13.00 and 20.00 hrs on the same day and at the end of
      light therapy. RESULTS: BDNF levels declined over the course of the day both in
      serum and saliva, and a correlation between diurnal BDNF trend and personality
      traits and habits characterizing the morning and evening types in healthy women
      was found. CONCLUSIONS: The present study is one of the first to show measurable
      BDNF in human saliva and to demonstrate its daily fluctuations in both saliva and
      serum of healthy young women. The correlation between diurnal changes in BDNF and
      the personality traits associated with body rhythms corroborates the notion that
      salivary BDNF may be a useful biomarker for stress-related research and different
      clinical investigations.

PMID- 23160114
TI  - Life-saving electroconvulsive therapy in a patient with near-lethal catatonia.
AB  - A young woman with bipolar I disorder and comorbid catatonia on enteral nutrition
      from several months, developed a form of near-lethal catatonia with weight loss,
      pressure sores, muscle atrophy, electrolyte imbalance, and depression of vital
      signs. A compulsory treatment was necessary, and informed consent was obtained
      from her mother for electroconvulsive therapy (ECT). After 7 ECT sessions, the
      patient recovered and resumed feeding. ECT may save the life of a patient with
      catatonia provided that legal obstacles are overcome. Clinicians should carefully
      evaluate patients with near-lethal catatonia, taking into account the risk of
      pulmonary embolism and other fatal events. The medical-legal issues, which vary
      across state regulations, should be addressed in detail to avoid unnecessary and
      potentially harmful delay in intervention.

PMID- 23160115
TI  - Why share data? Lessons learned from the fMRIDC.
AB  - Neuroimaging and the discipline of cognitive neuroscience have grown together in
      lock-step with each pushing the other toward an improved ability to explore and
      examine brain function and form. However successful neuroimaging and the
      examination of cognitive processes may seem today, the culture of data sharing in
      these fields remains underdeveloped. In this article, we discuss our own
      experience in the development of the fMRI Data Center (fMRIDC) - a large-scale
      effort to gather, curate, and openly share the complete data sets from published
      research articles of brain activation studies using fMRI. We outline the fMRIDC
      effort's beginnings, how it operated, note some of the sociological reactions we
      received, and provide several examples of prominent new studies performed using
      data drawn from the archive. Finally, we provide comment on what considerations
      are needed for successful neuroimaging databasing and data sharing as existing
      and emerging efforts take the next steps in archiving and disseminating the
      field's valuable and irreplaceable data. 

PMID- 23160116
TI  - On evidence, biases and confounding factors: Response to commentaries.
AB  - In a critical review (Thomas and Baker, 2012), we argued for caution in
      evaluating reports of training-dependent adult structural plasticity measured
      with MRI. Here, we respond to the commentaries on our review, clarifying our
      position and addressing some of the specific criticisms raised.

PMID- 23160117
TI  - TNF-alpha and soluble forms of TNF receptors 1 and 2 in the serum of patients
      with Crohn's disease and ulcerative colitis.
AB  - INTRODUCTION: Soluble forms of tumor necrosis factor (TNF) membrane receptors 1
      and 2 (sTNFR1 and sTNFR2) are present in body fluids. Their higher concentrations
      are observed in a number of diseases, including inflammatory bowel diseases
      (IBDs). sTNFR1 and sTNFR2 are capable of binding TNF-alpha, acting as an
      inhibitor that competes with a membrane receptor. The results of the available
      studies on sTNFR1 and sTNFR2 concentrations in IBDs and their association with
      disease activity are ambiguous. OBJECTIVES: The aim of the study was to assess
      sTNFR1 and sTNFR2 concentrations and their correlation with disease activity in
      patients with IBD. PATIENTS AND METHODS: Plasma levels of TNF-alpha, sTNFR1, and
      sTNFR2 were measured in 55 consecutive patients with ulcerative colitis (UC), 50
      subjects with Crohn's disease (CD), and 41 healthy controls. We assessed the
      associations of those markers with other inflammatory markers, disease activity
      and location, type of treatment, and complications. RESULTS: Positive
      correlations were observed between CD activity and sTNFR1 and sTNFR2 levels (r =
      0.42 for both, P <0.01) as well as between UC activity and sTNFR1 and sTNFR2
      levels (r = 0.63, P <0.0001; r = 0.47, P <0.001; respectively). TNF-alpha levels
      correlated only with CD activity (r = 0.29, P <0.05). In patients with nonactive
      UC, higher sTNFR2 levels were observed compared with controls. In patients with
      CD, higher TNF-alpha and sTNFR2 levels were demonstrated in patients who
      developed complications. CONCLUSIONS: sTNFR1 and sTNFR2 are more sensitive
      inflammatory markers than TNF-alpha in the assessment of disease activity in
      patients with CD and UC. Higher sTNFR2 levels are observed in patients with CD
      and complications.

PMID- 23160118
TI  - Molecular analysis of human and canine Staphylococcus aureus strains reveals
      distinct extended-host-spectrum genotypes independent of their methicillin
      resistance.
AB  - Staphylococcus aureus causes a wide range of infectious diseases in humans and
      various animal species. Although presumptive host-specific factors have been
      reported, certain genetic lineages seem to lack specific host tropism, infecting
      a broad range of hosts. Such Extended-Host-Spectrum Genotypes (EHSGs) have been
      described in canine infections, caused by common regional human methicillin
      resistant S. aureus (MRSA) lineages. However, information is scarce about the
      occurrence of methicillin-susceptible S. aureus (MSSA) EHSGs. To gain deeper
      insight into EHSG MSSA and EHSG MRSA of human and canine origin, a comparative
      molecular study was carried out, including a convenience sample of 120 current S.
      aureus (70 MRSA and 50 MSSA) isolates obtained from infected dogs. spa typing
      revealed 48 different spa types belonging to 16 different multilocus sequence
      typing clonal complexes (MLST-CCs). Based on these results, we further compared a
      subset of canine (n = 48) and human (n = 14) strains, including isolates of
      clonal complexes CC5, CC22, CC8, CC398, CC15, CC45, and CC30 by macrorestriction
      (pulsed-field gel electrophoresis [PFGE]) and DNA-microarray analysis. None of
      the methods employed was able to differentiate between clusters of human and
      canine strains independently of their methicillin resistance. In contrast, DNA
      microarray analysis revealed 79% of the 48 canine isolates as carriers of the
      bacteriophage-encoded human-specific immune evasion cluster (IEC). In conclusion,
      the high degree of similarity between human and canine S. aureus strains
      regardless of whether they are MRSA or MSSA envisions the existence of common
      genetic traits that enable these strains as EHSGs, challenging the concept of
      resistance-driven spillover of MRSA.

PMID- 23160119
TI  - Characterization of newcastle disease viruses in wild and domestic birds in
      Luxembourg from 2006 to 2008.
AB  - Newcastle disease virus (NDV) is one of the most important viral diseases of
      birds. Wild birds constitute a natural reservoir of low-virulence viruses, while
      poultry are the main reservoir of virulent strains. Exchange of virus between
      these reservoirs represents a risk for both bird populations. Samples from wild
      and domestic birds collected between 2006 and 2010 in Luxembourg were analyzed
      for NDV. Three similar avirulent genotype I strains were found in ducks during
      consecutive years, suggesting that the virus may have survived and spread
      locally. However, separate introductions cannot be excluded, because no recent
      complete F gene sequences of genotype I from other European countries are
      available. Detection of vaccine-like strains in wild waterbirds suggested the
      spread of vaccine strains, despite the nonvaccination policy in Luxembourg. Among
      domestic birds, only one chicken was positive for a genotype II strain differing
      from the LaSota vaccine and exhibiting a so-far-unrecognized fusion protein
      cleavage site of predicted low virulence. Three genotype VI strains from pigeons
      were the only virulent strains found. The circulation of NDV in wild and free
      ranging domestic birds warrants continuous surveillance because of increased
      concern that low-virulence wild-bird viruses could become more virulent in
      domestic populations.

PMID- 23160120
TI  - Distribution of Clostridium botulinum type E strains in Nunavik, Northern Quebec,
      Canada.
AB  - The distribution and levels of Clostridium botulinum type E were determined from
      field sites used by Inuit hunters for butchering seals along the coast of
      Nunavik. The incidence rates of C. botulinum type E in shoreline soil along the
      coast were 0, 50, and 87.5% among samples tested for the Hudson Strait, Hudson
      Bay, and Ungava Bay regions, respectively. Spores were detected in seawater or
      coastal rock surfaces from 17.6% of butchering sites, almost all of which were
      located in southern Ungava Bay. Concentrations of C. botulinum type E along the
      Ungava Bay coast were significantly higher than on the coasts of Hudson Strait
      and Hudson Bay, with the highest concentrations (270 to 1,800/kg of sample) found
      near butchering sites located along the mouths of large rivers. The Koksoak River
      contained high levels of C. botulinum type E, with the highest median
      concentration (270/kg) found in sediments of the marine portion of the river. C.
      botulinum type E was found in the intestinal contents (4.4%) and skins (1.4%) of
      seals. A high genetic biodiversity of C. botulinum type E isolates was observed
      among the 21 butchering sites and their surroundings along the Nunavik coastline,
      with 83% of isolates (44/53) yielding distinct pulsed-field gel electrophoresis
      genotypes. Multiple sources of C. botulinum type E may be involved in the
      contamination of seal meat during butchering in this region, but the risk of
      contamination appears to be much higher from environmental sources along the
      shoreline of southern Ungava Bay and the sediments of the Koksoak River.

PMID- 23160121
TI  - Mycobacteriophage Ms6 LysA: a peptidoglycan amidase and a useful analytical tool.
AB  - Since the peptidoglycan isolated from Mycobacterium spp. is refractory to
      commercially available murolytic enzymes, possibly due to the presence of various
      modifications found on this peptidoglycan, the utility of a mycobacteriophage
      derived murolytic enzyme was assessed for an analysis of peptidoglycan from
      mycobacteria. We cloned, expressed, and purified the lysA gene product, a protein
      with homology to known peptidoglycan-degrading amidases, from bacteriophage Ms6.
      The recombinant protein was shown to cleave the bond between l-Ala and d-muramic
      acid of muramyl pentapeptide and to release up to 70% of the diaminopimelic acid
      present in the isolated mycobacterial cell wall. In contrast to lysozyme, which,
      in culture, inhibits the growth of both Mycobacterium smegmatis and Mycobacterium
      tuberculosis, LysA had no effect on the growth of either species. However, the
      enzyme is useful for solubilizing the peptide chains of isolated mycobacterial
      peptidoglycan for analysis. The data indicate that the stem peptides from M.
      smegmatis are heavily amidated, containing few free carboxylic acids, regardless
      of the cross-linking status.

PMID- 23160122
TI  - Comparative genomic analysis and benzene, toluene, ethylbenzene, and o-, m-, and
      p-xylene (BTEX) degradation pathways of Pseudoxanthomonas spadix BD-a59.
AB  - Pseudoxanthomonas spadix BD-a59, isolated from gasoline-contaminated soil, has
      the ability to degrade all six BTEX (benzene, toluene, ethylbenzene, and o-, m-,
      and p-xylene) compounds. The genomic features of strain BD-a59 were analyzed
      bioinformatically and compared with those of another fully sequenced
      Pseudoxanthomonas strain, P. suwonensis 11-1, which was isolated from cotton
      waste compost. The genome of strain BD-a59 differed from that of strain 11-1 in
      many characteristics, including the number of rRNA operons, dioxygenases,
      monooxygenases, genomic islands (GIs), and heavy metal resistance genes. A high
      abundance of phage integrases and GIs and the patterns in several other genetic
      measures (e.g., GC content, GC skew, Karlin signature, and clustered regularly
      interspaced short palindromic repeat [CRISPR] gene homology) indicated that
      strain BD-a59's genomic architecture may have been altered through horizontal
      gene transfers (HGT), phage attack, and genetic reshuffling during its
      evolutionary history. The genes for benzene/toluene, ethylbenzene, and xylene
      degradations were encoded on GI-9, -13, and -21, respectively, which suggests
      that they may have been acquired by HGT. We used bioinformatics to predict the
      biodegradation pathways of the six BTEX compounds, and these pathways were proved
      experimentally through the analysis of the intermediates of each BTEX compound
      using a gas chromatograph and mass spectrometry (GC-MS). The elevated abundances
      of dioxygenases, monooxygenases, and rRNA operons in strain BD-a59 (relative to
      strain 11-1), as well as other genomic characteristics, likely confer traits that
      enhance ecological fitness by enabling strain BD-a59 to degrade hydrocarbons in
      the soil environment.

PMID- 23160123
TI  - Systems engineering of tyrosine 195, tyrosine 260, and glutamine 265 in
      cyclodextrin glycosyltransferase from Paenibacillus macerans to enhance
      maltodextrin specificity for 2-O-(D)-glucopyranosyl-(L)-ascorbic acid synthesis.
AB  - In this work, the site saturation mutagenesis of tyrosine 195, tyrosine 260 and
      glutamine 265 in the cyclodextrin glycosyltransferase (CGTase) from Paenibacillus
      macerans was conducted to improve the specificity of CGTase for maltodextrin,
      which can be used as a cheap and easily soluble glycosyl donor for the synthesis
      of 2-O-d-glucopyranosyl-l-ascorbic acid (AA-2G). Specifically, the site
      saturation mutagenesis of three sites-tyrosine 195, tyrosine 260, and glutamine
      265-was performed, and it was found that the resulting mutants (containing the
      mutations Y195S [tyrosine -> serine], Y260R [tyrosine -> arginine], and Q265K
      [glutamine -> lysine]) produced higher AA-2G yields than the wild type and the
      other mutant CGTases when maltodextrin was used as the glycosyl donor.
      Furthermore, double and triple mutations were introduced, and four mutants
      (containing Y195S/Y260R, Y195S/Q265K, Y260R/Q265K, and Y260R/Q265K/Y195S) were
      obtained and evaluated for the capacity to produce AA-2G. The Y260R/Q265K/Y195S
      triple mutant produced the highest titer of AA-2G at 1.92 g/liter, which was 60%
      higher than that (1.20 g/liter) produced by the wild-type CGTase. The kinetics
      analysis of AA-2G synthesis by the mutant CGTases confirmed the enhanced
      maltodextrin specificity, and it was also found that compared with the wild-type
      CGTase, all seven mutants had lower cyclization activities and higher hydrolysis
      and disproportionation activities. Finally, the mechanism responsible for the
      enhanced substrate specificity was explored by structure modeling, which
      indicated that the enhancement of maltodextrin specificity may be related to the
      changes of hydrogen bonding interactions between the side chain of residue at the
      three positions (195, 260, and 265) and the substrate sugars. This work adds to
      our understanding of the synthesis of AA-2G and makes the Y260R/Q265K/Y195S
      mutant a good starting point for further development by protein engineering.

PMID- 23160124
TI  - Contribution of nitrate assimilation to the fitness of Pseudomonas syringae pv.
      syringae B728a on plants.
AB  - The ability of Pseudomonas syringae pv. syringae to use nitrate as a nitrogen
      source in culture and on leaves was assessed. Substantial amounts of leaf surface
      nitrate were detected directly and by use of a bioreporter of nitrate on bean
      plants grown with a variety of nitrogen sources. While a nitrate reductase
      mutant, P. syringae DeltanasB, exhibited greatly reduced growth in culture with
      nitrate as the sole nitrogen source, it exhibited population sizes similar to
      those of the wild-type strain on leaves. However, the growth of the DeltanasB
      mutant was much less than that of the wild-type strain when cultured in bean leaf
      washings supplemented with glucose, suggesting that P. syringae experiences
      primarily carbon-limited and only secondarily nitrogen-limited growth on bean
      leaves. Only a small proportion of the cells of a green fluorescent protein (GFP)
      based P. syringae nitrate reductase bioreporter, LK2(pOTNas4), exhibited
      fluorescence on leaves. This suggests that only a subset of cells experience high
      nitrate levels or that nitrate assimilation is repressed by the presence of
      ammonium or other nitrogenous compounds in many leaf locations. While only a
      subpopulation of P. syringae consumes nitrate at a given time on the leaves, the
      ability of those cells to consume this resource would be strongly beneficial to
      those cells, especially in environments in which nitrate is the most abundant
      form of nitrogen.

PMID- 23160125
TI  - Reconstruction of novel cyanobacterial siphovirus genomes from Mediterranean
      metagenomic fosmids.
AB  - Cellular metagenomes are primarily used for investigating microbial community
      structure and function. However, cloned fosmids from such metagenomes capture
      phage genome fragments that can be used as a source of phage genomes. We show
      that fosmid cloning from cellular metagenomes and sequencing at a high coverage
      is a credible alternative to constructing metaviriomes and allows capturing and
      assembling novel, complete phage genomes. It is likely that phages recovered from
      cellular metagenomes are those replicating within cells during sample collection
      and represent "active" phages, naturally amplifying their genomic DNA and
      increasing chances for cloning. We describe five sets of siphoviral contigs
      (MEDS1, MEDS2, MEDS3, MEDS4, and MEDS5), obtained by sequencing fosmids from the
      cellular metagenome of the deep chlorophyll maximum in the Mediterranean. Three
      of these represent complete siphoviral genomes and two represent partial ones.
      This is the first set of phage genomes assembled directly from cellular
      metagenomic fosmid libraries. They exhibit low sequence similarities to one
      another and to known siphoviruses but are remarkably similar in overall genome
      architecture. We present evidence suggesting they infect picocyanobacteria,
      likely Synechococcus. Four of these sets also define a novel branch in the
      phylogenetic tree of phage large subunit terminases. Moreover, some of these
      siphoviral groups are globally distributed and abundant in the oceans, comparable
      to some known myoviruses and podoviruses. This suggests that, as more siphoviral
      genomes become available, we will be better able to assess the abundance and
      influence of this diverse and polyphyletic group in the marine habitat.

PMID- 23160127
TI  - Use of flow cytometry for rapid, quantitative detection of poliovirus-infected
      cells via TAT peptide-delivered molecular beacons.
AB  - Rapid and efficient detection of viral infection is crucial for the prevention of
      disease spread during an outbreak and for timely clinical management. In this
      paper, the utility of Tat peptide-modified molecular beacons (MBs) as a rapid
      diagnostic tool for the detection of virus-infected cells was demonstrated. The
      rapid intracellular delivery mediated by the Tat peptide enabled the detection of
      infected cells within 30 s, reaching saturation in signal in 30 min. This rapid
      detection scheme was coupled with flow cytometry (FC), resulting in an automated,
      high-throughput method for the identification of virus-infected cells. Because of
      the 2-order-of-magnitude difference in fluorescence intensity between infected
      and uninfected cells, as few as 1% infected cells could be detected. Because of
      its speed and sensitivity, this approach may be adapted for the practical
      diagnosis of multiple viral infections.

PMID- 23160128
TI  - Improved production of L-threonine in Escherichia coli by use of a DNA scaffold
      system.
AB  - Despite numerous approaches for the development of l-threonine-producing strains,
      strain development is still hampered by the intrinsic inefficiency of metabolic
      reactions caused by simple diffusion and random collisions of enzymes and
      metabolites. A scaffold system, which can promote the proximity of metabolic
      enzymes and increase the local concentration of intermediates, was reported to be
      one of the most promising solutions. Here, we report an improvement in l
      threonine production in Escherichia coli using a DNA scaffold system, in which a
      zinc finger protein serves as an adapter for the site-specific binding of each
      enzyme involved in l-threonine production to a precisely ordered location on a
      DNA double helix to increase the proximity of enzymes and the local concentration
      of metabolites to maximize production. The optimized DNA scaffold system for l
      threonine production significantly increased the efficiency of the threonine
      biosynthetic pathway in E. coli, substantially reducing the production time for l
      threonine (by over 50%). In addition, this DNA scaffold system enhanced the
      growth rate of the host strain by reducing the intracellular concentration of
      toxic intermediates, such as homoserine. Our DNA scaffold system can be used as a
      platform technology for the construction and optimization of artificial metabolic
      pathways as well as for the production of many useful biomaterials.

PMID- 23160129
TI  - Profiling in situ microbial community structure with an amplification microarray.
AB  - The objectives of this study were to unify amplification, labeling, and
      microarray hybridization chemistries within a single, closed microfluidic chamber
      (an amplification microarray) and verify technology performance on a series of
      groundwater samples from an in situ field experiment designed to compare U(VI)
      mobility under conditions of various alkalinities (as HCO(3)(-)) during
      stimulated microbial activity accompanying acetate amendment. Analytical limits
      of detection were between 2 and 200 cell equivalents of purified DNA.
      Amplification microarray signatures were well correlated with 16S rRNA-targeted
      quantitative PCR results and hybridization microarray signatures. The succession
      of the microbial community was evident with and consistent between the two
      microarray platforms. Amplification microarray analysis of acetate-treated
      groundwater showed elevated levels of iron-reducing bacteria (Flexibacter,
      Geobacter, Rhodoferax, and Shewanella) relative to the average background
      profile, as expected. Identical molecular signatures were evident in the transect
      treated with acetate plus NaHCO(3), but at much lower signal intensities and with
      a much more rapid decline (to nondetection). Azoarcus, Thaurea, and
      Methylobacterium were responsive in the acetate-only transect but not in the
      presence of bicarbonate. Observed differences in microbial community composition
      or response to bicarbonate amendment likely had an effect on measured rates of U
      reduction, with higher rates probable in the part of the field experiment that
      was amended with bicarbonate. The simplification in microarray-based work flow is
      a significant technological advance toward entirely closed-amplicon microarray
      based tests and is generally extensible to any number of environmental monitoring
      applications.

PMID- 23160130
TI  - Characterization and molecular epidemiology of a fungal infection of edible crabs
      (Cancer pagurus) and interaction of the fungus with the dinoflagellate parasite
      Hematodinium.
AB  - This study reports on an emerging fungal disease of the edible crab, Cancer
      pagurus. Juvenile (prerecruit) crabs were found to be subject to this disease
      condition during the months of May to September at two intertidal sites in South
      Wales, United Kingdom. Histopathology revealed that the fungi overwhelm the host
      response in the tissues, leading to progressive septicemia. The causative agent
      of this infection was isolated and grown in pure culture and was identified as a
      member of the Ophiocordyceps clade by sequencing of the small subunit of the
      fungal ribosomal DNA (rDNA). Of the crabs naturally infected with the fungus, 94%
      had a coinfection with the parasitic dinoflagellate Hematodinium species. To
      determine if there was any interaction between the two disease-causing agents,
      apparently fungus-free crabs, both with and without natural Hematodinium
      infections, were challenged with the fungal isolate. The presence of Hematodinium
      caused a significant reduction in fungal multiplication in the hemocoel of the
      crabs in comparison to that in Hematodinium-free individuals. Histopathology of
      coinfected crabs showed a systemic multiplication of Hematodinium within host
      tissues, leading to a rapid death, while Hematodinium-free crabs experimentally
      infected with the fungal isolate died due to fungal sepsis (septicemia) with the
      same characteristic pathology as seen in natural infections.

PMID- 23160126
TI  - Molecular diversity of Bacteroidales in fecal and environmental samples and swine
      associated subpopulations.
AB  - Several swine-specific microbial source tracking methods are based on PCR assays
      targeting Bacteroidales 16S rRNA gene sequences. The limited application of these
      assays can be explained by the poor understanding of their molecular diversity in
      fecal sources and environmental waters. In order to address this, we studied the
      diversity of 9,340 partial (>600 bp in length) Bacteroidales 16S rRNA gene
      sequences from 13 fecal sources and nine feces-contaminated watersheds. The
      compositions of major Bacteroidales populations were analyzed to determine which
      host and environmental sequences were contributing to each group. This
      information allowed us to identify populations which were both exclusive to swine
      fecal sources and detected in swine-contaminated waters. Phylogenetic and
      diversity analyses revealed that some markers previously believed to be highly
      specific to swine populations are shared by multiple hosts, potentially
      explaining the cross-amplification signals obtained with nontargeted hosts. These
      data suggest that while many Bacteroidales populations are cosmopolitan, others
      exhibit a preferential host distribution and may be able to survive different
      environmental conditions. This study further demonstrates the importance of
      elucidating the diversity patterns of targeted bacterial groups to develop more
      inclusive fecal source tracking applications.

PMID- 23160131
TI  - Carriage and fecal counts of cefotaxime M-producing Escherichia coli in pigs: a
      longitudinal study.
AB  - Current knowledge on extended-spectrum beta-lactamases (ESBLs) in animals is
      based largely on cross-sectional studies and qualitative data. The aim of this
      longitudinal study was to elucidate carriage proportions and fecal counts of ESBL
      producing Escherichia coli in pigs during the production cycle. At each of three
      ESBL-positive single-sited farrow-to-finisher pig farms (farms A, B, and C)
      included in the study, individual fecal samples were taken from 17 to 20 sows 1
      week before farrowing and from 2 piglets of each sow's litter four times from
      birth to slaughter (as piglets, weaners, and finishers). Cefotaxime (CTX)
      resistant coliforms in feces were counted on MacConkey agar containing 2 MUg/ml
      CTX and characterized for the presence of ESBL-encoding genes by PCR and
      sequencing. CTX-M-positive pigs were detected in all age groups at farms A
      (bla(CTX-M-9) group, compatible with bla(CTX-M-14/17)) and B (bla(CTX-M-1) group,
      compatible with bla(CTX-M-1/61)), whereas only three weaners were positive at
      farm C (bla(CTX-M-1) group, compatible with bla(CTX-M-1/61)). A significant
      decrease in carriage was detected during the production cycle, with on average
      50% carriage immediately after birth, 58% just before weaning, 29% during
      weaning, and 12% during finishing. The observed reduction in numbers of CTX-M
      positive pigs was accompanied by a significant reduction in mean fecal counts of
      CTX-resistant coliforms from ~10(7) CFU/g in piglets to ~10(3) CFU/g in finishers
      (P < 0.001). These findings provide novel information about the epidemiology of
      ESBLs at the farm level and have important implications for assessments of risks
      of meat contamination during slaughter.

PMID- 23160132
TI  - Biological and physicochemical wastewater treatment processes reduce the
      prevalence of virulent Escherichia coli.
AB  - Effluents discharged from wastewater treatment plants are possible sources of
      pathogenic bacteria, including Escherichia coli, in the freshwater environment,
      and determining the possible selection of pathogens is important. This study
      evaluated the impact of activated sludge and physicochemical wastewater treatment
      processes on the prevalence of potentially virulent E. coli. A total of 719 E.
      coli isolates collected from four municipal plants in Quebec before and after
      treatment were characterized by using a customized DNA microarray to determine
      the impact of treatment processes on the frequency of specific pathotypes and
      virulence genes. The percentages of potentially pathogenic E. coli isolates in
      the plant influents varied between 26 and 51%, and in the effluents, the
      percentages were 14 to 31%, for a reduction observed at all plants ranging
      between 14 and 45%. Pathotypes associated with extraintestinal pathogenic E. coli
      (ExPEC) were the most abundant at three of the four plants and represented 24% of
      all isolates, while intestinal pathogenic E. coli pathotypes (IPEC) represented
      10% of the isolates. At the plant where ExPEC isolates were not the most
      abundant, a large number of isolates were classified as both ExPEC and IPEC;
      overall, 6% of the isolates were classified in both groups, with the majority
      being from the same plant. The reduction of the proportion of pathogenic E. coli
      could not be explained by the preferential loss of one virulence gene or one type
      of virulence factor; however, the quinolone resistance gene (qnrS) appears to
      enhance the loss of virulence genes, suggesting a mechanism involving the loss of
      pathogenicity islands.

PMID- 23160133
TI  - Diverse microhabitats experienced by Halomonas variabilis on salt-secreting
      leaves.
AB  - The leaf surfaces of the salt-excreting tree Tamarix aphylla harbor a wide
      diversity of halophilic microorganisms, including Halomonas sp., but little is
      known of the factors that shape community composition in this extreme habitat. We
      isolated a strain of Halomonas variabilis from the leaf surface of T. aphylla and
      used it to determine the heterogeneity of salt concentrations experienced by
      bacteria in this environment. This halophilic strain was transformed with a
      proU::gfp reporter gene fusion, the fluorescence of which was responsive to NaCl
      concentrations up to 200 g liter(-1). These bioreporting cells were applied to T.
      aphylla leaves and were subsequently recovered from dew droplets adhering to the
      leaf surface. Although cells from within a given dew droplet exhibited similar
      green fluorescent protein fluorescence, the fluorescence intensity varied between
      droplets and was correlated with the salt concentration measured in each drop.
      Growth of H. variabilis was observed in all droplets, regardless of the salt
      concentration. However, cells found in desiccated microniches between dew drops
      were low in abundance and generally dead. Other bacteria recovered from T.
      aphylla displayed higher desiccation tolerance than H. variabilis, both in
      culture and on inoculated plants, despite having lower osmotic tolerance. Thus,
      the Tamarix leaf surface can be described as a salty desert with occasional oases
      where water droplets form under humid conditions. While halotolerant bacteria
      such as Halomonas grow in high concentrations of salt in such wet microniches,
      other organisms are better suited to survive desiccation in sites that are not
      wetted.

PMID- 23160134
TI  - Nontuberculous mycobacteria, fungi, and opportunistic pathogens in unchlorinated
      drinking water in The Netherlands.
AB  - The multiplication of opportunistic pathogens in drinking water supplies might
      pose a threat to public health. In this study, distributed unchlorinated drinking
      water from eight treatment plants in the Netherlands was sampled and analyzed for
      fungi, nontuberculous mycobacteria (NTM), and several opportunistic pathogens by
      using selective quantitative PCR methods. Fungi and NTM were detected in all
      drinking water samples, whereas Legionella pneumophila, Pseudomonas aeruginosa,
      Stenotrophomonas maltophilia, and Aspergillus fumigatus were sporadically
      observed. Mycobacterium avium complex and Acanthamoeba spp. were not detected.
      Season had no influence on the occurrence of these organisms, except for NTM and
      S. maltophilia, which were present in higher numbers in the summer. Opportunistic
      pathogens were more often observed in premise plumbing water samples than in
      samples from the distribution system. The lowest number of these organisms was
      observed in the finished water at the plant. Thus, fungi, NTM, and some of the
      studied opportunistic pathogens can multiply in the distribution and premise
      plumbing systems. Assimilable organic carbon (AOC) and/or total organic carbon
      (TOC) had no clear effects on fungal and NTM numbers or on P. aeruginosa- and S.
      maltophilia-positive samples. However, L. pneumophila was detected more often in
      water with AOC concentrations above 10 MUg C liter(-1) than in water with AOC
      levels below 5 MUg C liter(-1). Finally, samples that contained L. pneumophila,
      P. aeruginosa, or S. maltophilia were more frequently positive for a second
      opportunistic pathogen, which shows that certain drinking water types and/or
      sampling locations promote the growth of multiple opportunistic pathogens.

PMID- 23160135
TI  - Contribution of bacillomycin D in Bacillus amyloliquefaciens SQR9 to antifungal
      activity and biofilm formation.
AB  - Bacillus amyloliquefaciens strains are capable of suppressing soilborne pathogens
      through the secretion of an array of lipopeptides and root colonization, and
      biofilm formation ability is considered a prerequisite for efficient root
      colonization. In this study, we report that one of the lipopeptide compounds
      (bacillomycin D) produced by the rhizosphere strain Bacillus amyloliquefaciens
      SQR9 not only plays a vital role in the antagonistic activity against Fusarium
      oxysporum but also affects the expression of the genes involved in biofilm
      formation. When the bacillomycin D and fengycin synthesis pathways were
      individually disrupted, mutant SQR9M1, which was deficient in the production of
      bacillomycin D, only showed minor antagonistic activity against F. oxysporum, but
      another mutant, SQR9M2, which was deficient in production of fengycin, showed
      antagonistic activity equivalent to that of the wild-type strain of B.
      amyloliquefaciens SQR9. The results from in vitro, root in situ, and quantitative
      reverse transcription-PCR studies demonstrated that bacillomycin D contributes to
      the establishment of biofilms. Interestingly, the addition of bacillomycin D
      could significantly increase the expression levels of kinC gene, but KinC
      activation is not triggered by leaking of potassium. These findings suggest that
      bacillomycin D contributes not only to biocontrol activity but also to biofilm
      formation in strain B. amyloliquefaciens SQR9.

PMID- 23160136
TI  - Dynamics and diversity of Escherichia coli in animals and system management of
      the manure on a commercial farrow-to-finish pig farm.
AB  - The objective of this study was to determine the dynamics and diversity of
      Escherichia coli populations in animal and environmental lines of a commercial
      farrow-to-finish pig farm in Spain along a full production cycle (July 2008 to
      July 2009), with special attention to antimicrobial resistance and the presence
      of integrons. In the animal line, a total of 256 isolates were collected from
      pregnant sows (10 samples and 20 isolates), 1-week-old piglets (20 samples and 40
      isolates), unweaned piglets (20 samples and 38 isolates), growers (20 samples and
      40 isolates), and the finishers' floor pen (6 samples and 118 isolates); from the
      underfloor pits and farm slurry tank environmental lines, 100 and 119 isolates,
      respectively, were collected. Our results showed that E. coli populations in the
      pig fecal microbiota and in the farm environment are highly dynamic and show high
      levels of diversity. These issues have been proven through DNA-based typing data
      (repetitive extragenic palindromic PCR [REP-PCR]) and phenotypic typing data
      (antimicrobial resistance profile comprising 19 antimicrobials). Clustering of
      the sampling groups based on their REP-PCR typing results showed that the spatial
      features (the line) had a stronger weight than the temporal features (sampling
      week) for the clustering of E. coli populations; this weight was less significant
      when clustering was performed based on resistotypes. Among animals, finishers
      harbored an E. coli population different from those of the remaining animal
      populations studied, considering REP-PCR fingerprints and resistotypes. This
      population, the most important from a public health perspective, demonstrated the
      lowest levels of antimicrobial resistance and integron presence.

PMID- 23160137
TI  - Temperature- and salinity-decoupled overproduction of hydroxyectoine by
      Chromohalobacter salexigens.
AB  - Hydroxyectoine overproduction by the natural producer Chromohalobacter salexigens
      is presented in this study. Genetically engineered strains were constructed that
      at low salinity coexpressed, in a vector derived from a native plasmid, the
      ectoine (ectABC) and hydroxyectoine (ectD) genes under the control of the ectA
      promoter, in a temperature-independent manner. Hydroxyectoine production was
      further improved by increasing the copies of ectD and using a C. salexigens
      genetic background unable to synthesize ectoines.

PMID- 23160139
TI  - A luminescent hydrogel based on a new Au(I) complex.
AB  - The reaction of the water soluble phosphine 1,3,5-triaza-7-phosphaadamantane
      (PTA) with [Au(C=C-C(5)H(4)N)](n) yields the highly luminescent water soluble
      [(PTA)Au(4-pyridylethynyl)] complex. A detailed analysis of the compound shows
      the formation of gel structure giving rise to very long fibers, being the first
      example reported with such a simple structure.

PMID- 23160138
TI  - Unusual presentation of sacrococcygeal teratomas and associated malformations in
      children: clinical experience and review of the literature.
AB  - BACKGROUND: Sacrococcygeal teratomas are the most common and best known
      extragonadal teratomas in neonates and infants, but they sometimes present
      unique, distinctive features unlike those commonly described, that can be
      considered exceptional and noteworthy. MATERIAL AND METHODS: The Authors reviewed
      the most significant (Table I, II) clinical, laboratory, radiological and
      pathologic findings, surgical procedure, and early and long-term results in 5
      children, 2 males and 3 females, suffering from sacrococcygeal teratomas. Four of
      5 patients were observed and managed in the neonatal age. A prenatal diagnosis
      had already been made in 2 of them between the 2nd and 3rd trimester of
      pregnancy. Two patients were also suffering from the Currarino syndrome
      associated with Hirschsprung's disease and other, multiple malformations and a
      cloacal anomaly with anal imperforation, respectively. This last developmental
      anomaly had been prenatally suspected at US scanning, which had demonstrated a
      severe sacral anomaly and a large abdominal mass with perineal extension and
      dilated bowel loops. All the infants were born by scheduled caesarean section in
      a tertiary care hospital and were then referred to the N.I.C.Us. because of a
      mostly acute clinical presentation, except for case N degrees 4, who was referred
      at the age of 3.3 years. Laboratory and radiologic investigations confirmed the
      clinical diagnosis of teratoma on the basis of elevated AFP values and imaging
      findings. All patients underwent emergency surgical management, in accordance
      with recommended practice, consisting of complete exeresis of the tumor,
      including coccygectomy, in 3 of the 5 children. RESULTS: Of the 5 patients, the
      female newborn affected by the Currarino syndrome, associated with persistence of
      the common cloacal canal and anal imperforation, died two days after surgery, of
      cardiovascular and respiratory complications. All the other patients had an
      uneventful postoperative course. Two years after the first exeresis at birth,
      relapse was observed in case N degrees  3, with a malignant component, YST,
      anticipated by elevated AFP values but negative physical signs and a benign
      cystic imaging pattern. After adjuvant chemotherapy she underwent a second
      complete exeresis. So far, 3 years after the second surgery and 5 years after the
      diagnosis and first treatment, no local recurrence or distant metastases have
      occurred. The other 3 patients are also all alive, disease-free and with no signs
      of relapse or distant metastasis, after a follow-up ranging from 2 years to 28
      years. None of the 3 cases treated for sacrococcygeal teratoma, operated in 1985,
      1984 and 2006, have ever developed functional sequelae such as ano-rectal and/or
      bladder dysfunction or hypotonia of the lower limbs. CONCLUSIONS: From this
      review of our selected cases and in the light of literature reports, we can draw
      the following conclusions. Some sacrococcygeal teratomas may have unique
      characteristics distinguishing them from more common cases, especially those
      included in the Currarino Syndrome, with or without an association with other
      malformations such as Hirschsprung's Disease and Cloacal anomalies. Being
      congenital tumors, prenatal diagnosis by US scan is extremely important in order
      to decide either for an anticipated delivery or to perform, in critical fetuses,
      prenatal treatment within highly specialized facilities, or to organize proper
      perinatal care, always in appropriate facilities where it is possible to define
      the diagnosis and carry out emergency surgery. An emergency procedure is
      frequently dictated both by complications related to the mass effect, and by the
      need to define the histology of the whole mass rather than just small biopsy
      specimens. Some sacrococcygeal teratomas can hide more or less extensive islands
      of immaturity or signs of malignant transformation that are clinically evident.
      The prognosis is generally benign, although AIEOP (Associazione Italiana
      Ematologia Oncologica Pediatrica) 2004 guidelines pointed out that high levels of
      circulating markers, including AFP, in children affected by mature or immature
      teratomas would indicate the presence of micro-foci of YST, marking them out as
      at high risk. The UKCCSG II (Children UK Cancer Study Group) and the SFOP
      (Societe Francaise d'Oncologie Pediatrique) indicated AFP values exceeding 10,000
      ng / ml as the threshold identifying a group of patients with severe prognosis.
      The treatment indicated is early, complete exeresis, followed by a careful,
      extensive microscopic examination associated, if necessary, with adjuvant
      chemotherapy, that is indicated before surgery only in infiltrating primary
      malignant teratomas. Sacrococcygeal teratomas are commonly considered as lesions
      at particular risk, in which the coccyx must always be removed together with the
      mass and overlying skin, taking particular care of the deep pelvic fascia to
      prevent functional disorders of the bladder and anal canal, as well as any motor
      alterations of the lower limbs, usually due to iatrogenic lesions of the
      subfascial nerve structures. There is a ananimous consensus that to improve the
      prognosis, close, long-term clinical, laboratory and imaging surveillance is
      essential at shorter intervals during the first 5 years after the exeresis and
      annually thereafter. In newborns or infants suffering from congenital
      malformations associated with teratomas, definitive surgical correction, if
      indicated, must obviously be postponed to a proper time, especially in patients
      with multiple malformations or needing adjuvant chemotherapy, unless a
      complication arises or the repair cannot be delayed.

PMID- 23160140
TI  - The immunosuppressive agents rapamycin, cyclosporin A and tacrolimus increase
      lipolysis, inhibit lipid storage and alter expression of genes involved in lipid
      metabolism in human adipose tissue.
AB  - Cyclosporin A (CsA), tacrolimus and rapamycin are immunosuppressive agents (IAs)
      associated with insulin resistance and dyslipidemia, although their molecular
      effects on lipid metabolism in adipose tissue are unknown. We explored IAs
      effects on lipolysis, lipid storage and expression of genes involved on lipid
      metabolism in isolated human adipocytes and/or adipose tissue obtained via
      subcutaneous and omental fat biopsies. CsA, tacrolimus and rapamycin increased
      isoproterenol-stimulated lipolysis and inhibited lipid storage by 20-35% and
      enhanced isoproterenol-stimulated hormone-sensitive lipase Ser552
      phosphorylation. Rapamycin also increased basal lipolysis (~20%) and impaired
      insulin's antilipolytic effect. Rapamycin, down-regulated the gene expression of
      perilipin, sterol regulatory element-binding protein 1 (SREBP1) and lipin 1,
      while tacrolimus down-regulated CD36 and aP2 gene expression. All three IAs
      increased IL-6 gene expression and secretion, but not expression and secretion of
      TNF-alpha or adiponectin. These findings suggest that CsA, tacrolimus and
      rapamycin enhance lipolysis, inhibit lipid storage and expression of lipogenic
      genes in adipose tissue, which may contribute to the development of dyslipidemia
      and insulin resistance associated with immunosuppressive therapy.

PMID- 23160141
TI  - Modelling auxin efflux carrier phosphorylation and localization.
AB  - Regulation of the activity and localization of PIN-FORMED (PIN) membrane
      proteins, which facilitate efflux of the plant hormone auxin from cells, is
      important for plants to respond to environmental stimuli and to develop new
      organs. The protein kinase PINOID (PID) is involved in regulating PIN
      phosphorylation, and this is thought to affect PIN localization by biasing
      recycling towards shootwards (apical) (rather than rootwards (basal)) membrane
      domains. PID has been observed to undergo transient internalization following
      auxin treatment, and it has been suggested that this may be a result of calcium
      dependent sequestration of PID by the calcium-binding protein TOUCH3 (TCH3). We
      present a mathematical formulation of these processes and examine the resulting
      steady-state and time-dependent behaviours in response to transient increases in
      cytosolic calcium. We further combine this model with one for the recycling of
      PINs in polarized cells and also examine its behaviour. The results provide
      insight into the behaviour observed experimentally and provide the basis for
      subsequent studies of the tissue-level implications of these subcellular
      processes for phenomena such as gravitropism.

PMID- 23160143
TI  - Looking for chemical reaction networks exhibiting a drift along a manifold of
      marginally stable states.
AB  - I recently reported some examples of mass-action equations that have a continuous
      manifold of marginally stable stationary states [Brogioli, D., 2010. Marginally
      stable chemical systems as precursors of life. Phys. Rev. Lett. 105, 058102;
      Brogioli, D., 2011. Marginal stability in chemical systems and its relevance in
      the origin of life. Phys. Rev. E 84, 031931]. The corresponding chemical reaction
      networks show nonclassical effects, i.e. a violation of the mass-action
      equations, under the effect of the concentration fluctuations: the chemical
      system drifts along the marginally stable states. I proposed that this effect is
      potentially involved in abiogenesis. In the present paper, I analyze the
      mathematical properties of mass-action equations of marginally stable chemical
      reaction networks. The marginal stability implies that the mass-action equations
      obey some conservation law; I show that the mathematical properties of the
      conserved quantity characterize the motion along the marginally stable stationary
      state manifold, i.e. they allow to predict if the fluctuations give rise to a
      random walk or a drift under the effect of concentration fluctuations. Moreover,
      I show that the presence of the drift along the manifold of marginally stable
      stationary-states is a critical property, i.e. at least one of the reaction
      constants must be fine tuned in order to obtain the drift.

PMID- 23160142
TI  - Information-theoretic uncertainty of SCFG-modeled folding space of the non-coding
      RNA.
AB  - RNA secondary structure ensembles define probability distributions for
      alternative equilibrium secondary structures of an RNA sequence. Shannon's
      entropy is a measure for the amount of diversity present in any ensemble. In this
      work, Shannon's entropy of the SCFG ensemble on an RNA sequence is derived and
      implemented in polynomial time for both structurally ambiguous and unambiguous
      grammars. Micro RNA sequences generally have low folding entropy, as previously
      discovered. Surprisingly, signs of significantly high folding entropy were
      observed in certain ncRNA families. More effective models coupled with targeted
      randomization tests can lead to a better insight into folding features of these
      families. AVAILABILITY: URL
      http://www.plantbio.uga.edu/~russell/index.php?s=1&n=5&r=0.

PMID- 23160144
TI  - Metal-binding properties and structural characterization of a self-assembled
      coiled coil: formation of a polynuclear Cd-thiolate cluster.
AB  - This paper describes the design, characterization, and metal-binding properties
      of a 32-residue polypeptide called AQ-C16C19. The sequence of this peptide is
      composed of four repeats of the seven residue sequence Ile-Ala-Ala-Leu-Glu-Gln
      Lys but with a Cys-X-X-Cys metal-binding motif substituted at positions 16-19.
      Size exclusion chromatography with multiangle light scattering detection (SEC
      MALS) and circular dichroism (CD) spectroscopy studies showed that the apo
      peptide exhibits a pH-dependent oligomerization state in which a three-stranded
      alpha-helical coiled coil is dominant between pH5.4 and 8.5. The Cd(2+)-binding
      properties of the AQ-C16C19 peptide were studied by ultraviolet-visible
      spectroscopy (UV-vis), electrospray ionization mass spectrometry (ESI MS), and
      (113)Cd NMR techniques. The holoprotein was found to contain a polynuclear
      cadmium-thiolate center formed within the hydrophobic core of the triple-stranded
      alpha-helical coiled-coil structure. The X-ray crystal structure of the Cd-loaded
      peptide, resolved at 1.85A resolution, revealed an adamantane-like configuration
      of the polynuclear metal center consisting of four cadmium ions, six thiolate
      sulfur ligands from cysteine residues and four oxygen-donor ligands. Three of
      these are from glutamic acid residues and one is from an exogenous water
      molecule. Thus, each cadmium ion is coordinated in a distorted tetrahedral S(3)O
      geometry. The metal cluster was found to form cooperatively at pH5.4 but in a
      stepwise fashion at pH>7. The results demonstrate that synthetic coiled-coils can
      be designed to incorporate multinuclear metal clusters, a proof-of-concept for
      their potential use in developing synthetic metalloenzymes and multi-electron
      redox agents.

PMID- 23160145
TI  - The New Zealand nurse specialist framework: clarifying the contribution of the
      nurse specialist.
AB  - Maximizing the contribution that nurses can make to the health care outcomes is
      the focus of health workforce planners and funders worldwide. New Zealand, along
      with many other countries, faces significant taxonomical challenges in developing
      specialist nursing workforce as nurse specialists and specialty areas of practice
      are inconsistently defined. Clearly defining and capturing data on current
      workforces is a challenge shared by many countries impacting on the ability to
      understand current supply and plan for anticipated increased demand. This article
      presents an overview of the New Zealand Nurse Specialist Framework (NZNSF)
      developed through a consensus approach as part of a doctoral study. The NZSNF has
      already been adopted by some national nursing groups in New Zealand and provides
      an overarching structure to support coherence, clarity and consistency for nurse
      specialists. The framework aims to support workforce policy makers in planning
      effective utilization of the nurse specialist in health care delivery.

PMID- 23160147
TI  - A thermodynamic model for the simultaneous charge/spin order transition in
      LaCu3Fe4O12.
AB  - LaCu(3)Fe(4)O(12) undergoes  a phase transition at 393 K from an
      antiferromagnetic insulating state at low temperatures to a paramagnetic metallic
      state above the critical temperature. We build a basic model for the electronic
      structure of this material that allows us to extract the mechanism that governs
      the transition and calculate the stability of the different phases. It also
      allows us to speculate on the effect of pressure on this material to build a T-p
      phase diagram.

PMID- 23160148
TI  - Programmable active droplet generation enabled by integrated pneumatic
      micropumps.
AB  - In this work we have investigated the integrated diaphragm micropump as an active
      fluidic control approach for the on-demand generation of droplets with precisely
      defined size, frequency and timing. In contrast to valve-actuated devices that
      only modulate the flow of the dispersed phase being continuously injected, this
      integrated micropump allows the combination of fluidic transport and modulation
      to achieve active control of droplet generation. A distinct characteristic of
      this method compared to the valve modulated droplet formation processes is that
      it enables independent control of droplet generation frequency by adjusting the
      pumping frequency and droplet size by flow conditions. We also demonstrated the
      generation of complex droplet patterns through programming the pumping
      configurations and the application to multi-volume digital PCR for precise and
      quantitative detection of genetic targets. Overall, our results suggest that the
      pump-based droplet microfluidics provide a robust platform for programmable
      active droplet generation which could facilitate the development of high
      performance chemical and biological assays.

PMID- 23160149
TI  - Randomized clinical trial of endovenous laser ablation versus conventional
      surgery for small saphenous varicose veins.
AB  - INTRODUCTION: No randomized clinical trial comparing treatment options for small
      saphenous vein (SSV) incompetence exists, and there is no clear evidence that
      this axis behaves the same as the great saphenous vein after treatment. This
      means that the existing literature base, centered on the treatment of great
      saphenous vein incompetence cannot simply be extrapolated to inform the
      management of SSV insufficiency. This trial compares the gold standard of
      conventional surgery and endovenous laser ablation (EVLA) in the management of
      SSV incompetence. METHODS: Patients with unilateral, primary saphenopopliteal
      junction incompetence and SSV reflux were randomized equally into parallel groups
      receiving either surgery or EVLA. Patients were assessed at baseline and weeks 1,
      6, 12, and 52. Outcomes included successful abolition of axial reflux on duplex,
      visual analog pain scores, recovery time, complication rates, Venous Clinical
      Severity Score, and quality of life profiling. RESULTS: A total of 106 patients
      were recruited and randomized to surgery (n = 53) or EVLA (n = 53). Abolition of
      SSV reflux was significantly higher after EVLA (96.2%) than surgery (71.7%) (P <
      0.001). Postoperative pain was significantly lower after EVLA (P < 0.05),
      allowing an earlier return to work and normal function (P < 0.001). Minor sensory
      disturbance was significantly lower in the EVLA group (7.5%) than in surgery
      (26.4%) (P = 0.009). Both groups demonstrated similar improvements in Venous
      Clinical Severity Score and quality of life. CONCLUSION: EVLA produced the same
      clinical benefits as conventional surgery but was more effective in addressing
      the underlying pathophysiology and was associated with less periprocedural
      morbidity allowing a faster recovery. ( REGISTRATION NUMBER: NCT00841178.).

PMID- 23160151
TI  - Alterations of global gastrointestinal motility after sleeve gastrectomy: a
      prospective study.
AB  - OBJECTIVES: To evaluate the role of sleeve gastrectomy (SG) in gastrointestinal
      motility. BACKGROUND: SG is a widely used bariatric operation leading to weight
      loss and early improvement of patient's metabolic profile. Current data indicate
      faster postoperative gastric emptying, but detailed studies on alterations in
      small bowel motility are missing. DESIGN: We evaluated 21 morbidly obese patients
      who underwent laparoscopic SG before and 4 months after the procedure. After
      consumption of a semisolid radiolabeled meal, their gastric and intestinal
      transit times were studied with a gamma camera. Particularly the times of 10%
      gastric emptying, 50% gastric emptying, maximal intestinal filling, 10% terminal
      ileum filling, duodenal to terminal ileum transit, cecal filling initiation, and
      ileocecal valve transit (T ICVt) were studied pre- and postoperatively. RESULTS:
      Ten percent gastric emptying and 50% gastric emptying were decreased
      postoperatively as well as maximal intestinal filling, indicating faster gastric
      emptying and intestinal filling. Duodenal to terminal ileum transit and 10%
      terminal ileum filling also decreased as small bowel transit time accelerated and
      the meal reached the terminal ileum more rapidly. Contrary opening of the
      ileocecal valve and food transit through it were delayed, with postoperative
      increase in cecal filling initiation and T ICVt, respectively. CONCLUSIONS: SG
      accelerates gastric emptying and small bowel transit of semisolids. In addition,
      it delays the initiation of cecal filling and T ICVt. This early and prolonged
      contact of food with the distal small bowel mucosa may explain the metabolic
      effects of SG occurring before substantial weight loss.

PMID- 23160150
TI  - Inhalation injury severity and systemic immune perturbations in burned adults.
AB  - OBJECTIVE: We aimed to determine whether the severity of inhalation injury evokes
      an immune response measurable at the systemic level and to further characterize
      the balance of systemic pro- and anti-inflammation early after burn and
      inhalation injury. BACKGROUND: Previously, we reported that the pulmonary
      inflammatory response is enhanced with worse grades of inhalation injury and that
      those who die of injuries have a blunted pulmonary immune profile compared with
      survivors. METHODS: From August 2007 to June 2011, bronchoscopy was performed on
      80 patients admitted to the burn intensive care unit when smoke inhalation was
      suspected. Of these, inhalation injury was graded into 1 of 5 categories (0, 1,
      2, 3, and 4), with grade 0 being the absence of visible injury and grade 4
      corresponding to massive injury. Plasma was collected at the time of bronchoscopy
      and analyzed for 28 immunomodulating proteins via multiplex bead array or enzyme
      linked immunosorbent assay. RESULTS: The concentrations of several plasma immune
      mediators were increased with worse inhalation injury severity, even after
      adjusting for age and % total body surface area (TBSA) burn. These included
      interleukin (IL)-1RA (P = 0.002), IL-6 (P = 0.002), IL-8 (P = 0.026), granulocyte
      colony-stimulating factor (P = 0.002), and monocyte chemotactic protein 1 (P =
      0.007). Differences in plasma immune mediator concentrations in surviving and
      deceased patients were also identified. Briefly, plasma concentrations of IL-1RA,
      IL-6, IL-8, IL-15, eotaxin, and monocyte chemotactic protein 1 were higher in
      deceased patients than in survivors (P < 0.05 for all), whereas IL-4 and IL-7
      were lower (P < 0.05). After adjusting for the effects of age, % TBSA burn, and
      inhalation injury grade, plasma IL-1RA remained significantly associated with
      mortality (odds ratio, 3.12; 95% confidence interval, 1.03-9.44). Plasma IL-1RA
      also correlated with % TBSA burn, inhalation injury grade, fluid resuscitation,
      Baux score, revised Baux score, Denver score, and the Sequential Organ Failure
      Assessment score. CONCLUSIONS: The severity of smoke inhalation injury has
      systemically reaching effects, which argue in favor of treating inhalation injury
      in a graded manner. In addition, several plasma immune mediators measured early
      after injury were associated with mortality. Of these, IL-1RA seemed to have the
      strongest correlation with injury severity and outcomes measures, which may
      explain the blunted pulmonary immune response we previously found in
      nonsurvivors.

PMID- 23160152
TI  - IL-25 improves IgA levels during parenteral nutrition through the JAK-STAT
      pathway.
AB  - INTRODUCTION: Parenteral nutrition (PN) impairs mucosal immunity and increases
      the risk of infection in part via lower IgA levels at mucosal surfaces. Transport
      of immunoglobulin A (IgA) across the mucosa to the gut lumen depends on the
      epithelial transport protein, polymeric immunoglobulin receptor (pIgR), which is
      reduced during PN. In vitro, studies demonstrate that IL-4 up-regulates pIgR
      production via Janus kinase/signal transducers and activators of transcription
      (JAK/STAT) signaling. Because IL-4 stimulates IgA and is reduced during PN, we
      hypothesized that the suppressed pIgR is a result of decreased JAK-1 and STAT-6
      phosphorylation. Because IL-4 is mediated by IL-25, we also hypothesized that PN
      + IL-25 would restore luminal IgA by increasing phosphorylated JAK-1 and STAT-6,
      resulting in increased tissue pIgR and luminal IgA. METHOD: Experiment 1: 2 days
      after intravenous cannulation, male Institute of Cancer Research mice were
      randomized to chow (n = 11) or PN (n = 9). Experiment 2: 2 days after intravenous
      cannulation, male Institute of Cancer Research mice were randomized to chow (n =
      12), PN (n = 10), or PN + 0.7 MUg of exogenous IL-25 (n = 11) per day. After 5
      days, distal ileum tissue was collected, homogenized, and protein extracted for
      JAK-STAT expression levels using a phospho-specific antibody microarray. Tissue
      was homogenized to measure pIgR expression via Western blot or fixed in 4%
      paraformaldehyde to measure pIgR expression via immunohistochemistry. Small
      intestinal wash fluid was collected and IgA was quantified using enzyme-linked
      immunosorbent assay. RESULTS: Experiment 1: PN significantly reduced
      phosphorylated JAK-1 and STAT-6 compared with chow. PN also decreased the tissue
      levels of the Th2 cytokines, IL-4 and IL-13, as well as pIgR, and luminal IgA
      compared with chow. Experiment 2: Exogenous administration of PN + IL-25
      increased the phosphorylated JAK-1 and STAT-6 compared with PN alone. IL-25
      completely restored expression of IL-13 to chow levels. IL-4, pIgR, IgA, and
      phosphorylated JAK-1 were significantly increased with IL-25 treatment compared
      with PN but failed to reach levels measured in chow. STAT-6 was significantly
      increased with IL-25 treatment compared with chow and PN. CONCLUSIONS: PN
      significantly decreases the JAK-STAT pathway by reducing levels of phosphorylated
      STAT-6 and JAK-1. Consistent with our previous work, sIgA, pIgR, and IL-4
      decreased with PN, whereas the addition of IL-25 to PN reversed these decreases
      and demonstrated the role of the JAK-STAT pathway in vivo during PN.

PMID- 23160158
TI  - An open-framework rutile-type magnesium isonicotinate and its structural analogue
      with an anatase topology.
AB  - Two new photoluminescent magnesium-based coordination polymers, Mg(int)(2).H(2)O
      (1) and Mg(nt)(2) (2), were synthesized under solvothermal conditions. Structural
      analyses reveal that they have different 3,6-connected frameworks with rutile-
      and anatase-type topologies, respectively. Compound 1 remains stable after the
      removal of its guest molecules and it exhibits weak ferroelectric behavior.

PMID- 23160153
TI  - Nitric oxide controls the immunopathology of tuberculosis by inhibiting NLRP3
      inflammasome-dependent processing of IL-1beta.
AB  - Interleukin 1 (IL-1) is an important mediator of innate immunity but can also
      promote inflammatory tissue damage. During chronic infections such as
      tuberculosis, the beneficial antimicrobial role of IL-1 must be balanced with the
      need to prevent immunopathology. By exogenously controlling the replication of
      Mycobacterium tuberculosis in vivo, we obviated the requirement for antimicrobial
      immunity and discovered that both IL-1 production and infection-induced
      immunopathology were suppressed by lymphocyte-derived interferon-gamma (IFN
      gamma). This effect was mediated by nitric oxide (NO), which we found
      specifically inhibited assembly of the NLRP3 inflammasome via thiol
      nitrosylation. Our data indicate that the NO produced as a result of adaptive
      immunity is indispensable in modulating the destructive innate inflammatory
      responses elicited during persistent infections.

PMID- 23160159
TI  - Infective endocarditis: a comprehensive overview.
AB  - Infective endocarditis (IE) is an infection of a heart valve or other cardiac
      structure at a site of endothelial damage. The definition has been also expanded
      to include infected cardiac devices. A variety of organ systems may be adversely
      affected in patients with IE. Although advances have improved the diagnostic
      accuracy for IE, morbidity and mortality remain remarkably high. This article
      reviews the pathophysiology, complications, diagnosis, and management of IE with
      recent updates to the literature and the major cardiovascular society guidelines.
      The increasingly prevalent clinical problem of intracardiac device-related IE is
      addressed, along with the recent changes to the IE prophylaxis guidelines.

PMID- 23160154
TI  - Trex1 regulates lysosomal biogenesis and interferon-independent activation of
      antiviral genes.
AB  - The sensing of viral nucleic acids by the innate immune system triggers the
      production of type I interferons, which activates interferon-stimulated genes
      (ISGs) and directs a multifaceted antiviral response. ISGs can also be activated
      through interferon-independent pathways, although the precise mechanisms remain
      elusive. Here we found that the cytosolic exonuclease Trex1 regulated the
      activation of a subset of ISGs independently of interferon. Both Trex1(-/-) mouse
      cells and Trex1-mutant human cells had high expression of genes encoding
      antiviral molecules ('antiviral genes') and were refractory to viral infection.
      The interferon-independent activation of antiviral genes in Trex1(-/-) cells
      required the adaptor STING, the kinase TBK1 and the transcription factors IRF3
      and IRF7. We also found that Trex1-deficient cells had an expanded lysosomal
      compartment, altered subcellular localization of the transcription factor TFEB
      and diminished activity of the regulator mTORC1. Together our data identify Trex1
      as a regulator of lysosomal biogenesis and interferon-independent activation of
      antiviral genes and show that dysregulation of lysosomes can elicit innate immune
      responses.

PMID- 23160160
TI  - California ACC goals.
AB  - MISSION: To advocate for accessible, highest quality, cost-effective
      cardiovascular care for Californians. The purpose of the Chapter shall be to
      contribute to the prevention of cardiovascular diseases, to ensure optimal
      quality care for the individuals with such diseases, and to foster the highest
      professional ethical standards.

PMID- 23160162
TI  - Biventricular pacing in normal hearts.
AB  - For more than half a century, pacemakers have proven to be one of the most
      successful medical interventions. In an effort to approximate normal cardiac
      physiology, pacemakers have evolved from simple to highly sophisticated devices.
      There is a growing demand, not only to improve overall mortality and safety in
      patients with existing devices, but also to improve patient quality of life. With
      growing evidence of left ventricular dysfunction and desychronization due to
      prolonged right ventricle apex (RVA) pacing, alternative ways to avoid excessive
      RVA pacing have been devised. In the pursuit of providing safe long-term pacing,
      biventricular pacing is emerging as an attractive option.

PMID- 23160163
TI  - Contribution of right ventricular dysfunction to heart failure mortality: a meta
      analysis.
AB  - Right ventricular systolic dysfunction (RVSD) has been related to prognosis in
      patients with heart failure (HF) and/or left ventricular systolic dysfunction.
      However, most of the studies addressing this issue are not large enough, have
      different inclusion criteria, and use different methods to evaluate RV function
      to draw definite conclusions. We sought to investigate the association between
      RVSD and outcomes in patients with left ventricular dysfunction. Eleven studies
      of 40 (27.5%), with 4732 patients, were included in the meta-analysis. RVSD was
      present in 2234 patients (47.2%). Four of the studies had admission for HF as an
      endpoint. We found a significant association between RVSD and overall mortality
      with significant between-studies heterogeneity and presence of publication bias
      (funnel plot). A significant association was found between RVSD and admission for
      HF. RVSD is associated with overall mortality and admission for HF during follow
      up. Significant between-studies heterogeneity and publication bias must be taken
      into account when interpreting this information.

PMID- 23160164
TI  - The biochemical aspects of a non-ST-segment elevation acute coronary syndrome.
AB  - The clinical course of an acute coronary syndrome can vary from relatively benign
      to potentially fatal. The biomarkers of myocardial necrosis relate to the amount
      of myocardial damage and are closely linked to a patient's prognosis. They are
      measured to help guide management decisions. Recent interest in myocardial
      neurohumoral mechanisms has identified the natriuretic peptides as strong
      prognostic biomarkers following an ischemic event. During an acute event they
      provide information regarding the area of myocardium at risk. The biomarkers of
      inflammation, such as C-reactive protein, are related to both the development of
      atherosclerosis and the risk of acute ischemic events. The mechanism
      characterizing the pathophysiology of the syndrome is represented by these
      cardiac biomarkers. Assessing combinations of pathobiologically diverse
      biomarkers may provide a better risk evaluation method and further dictate
      subsequent therapy.

PMID- 23160165
TI  - Management of blood glucose in patients with acute coronary syndromes.
AB  - Hyperglycemia during admission for acute myocardial infarction (MI) is common and
      associated with poor outcomes. Prior studies employed two distinct approaches to
      improve outcomes in patients with acute MI--one focused on glucose control, and
      the other on provision of glucose, insulin, and potassium. However, despite
      multiple largescale studies, the benefits of glucose lowering in the setting of
      acute MI remain unclear. This article reviews data from observational studies and
      clinical trials and synthesizes this information into practical recommendations
      based on available evidence.

PMID- 23160166
TI  - An update on antithrombotic therapy in atrial fibrillation: the role of newer and
      emergent drugs.
AB  - Atrial fibrillation (AF) is the most common cardiac arrhythmia and is associated
      with potentially dreadful cardioembolic complications such as stroke. The risk of
      stroke is stratified based on the patient's comorbid conditions using several
      scoring systems. Patients are treated with oral anticoagulation using warfarin or
      aspirin based on their cardioembolic stroke risk. Although warfarin has been the
      only effective therapy, it is underutilized clinically due to concern for
      multiple drug-to-drug and drug-to-food interactions and hemorrhagic
      complications. Dual antiplatelet therapy with aspirin and clopidogrel has been
      studied as a potential alternative anticoagulant for AF patients; however, the
      combination of aspirin and clopidogrel was noted to be inferior to warfarin in
      preventing strokes, with an increased risk of bleeding. As a result, newer
      anticoagulant agents, including direct thrombin inhibitors, direct and indirect
      factor Xa inhibitors, and vitamin K antagonists, have been developed and
      evaluated in AF patients. Results from a recent study demonstrated that high-dose
      dabigatran, a direct thrombin inhibitor, was superior to warfarin in preventing
      stroke and systemic embolism with similar bleeding risk. It ultimately received
      approval by the US Food and Drug Administration for stroke prophylaxis for
      nonvalvular AF patients. There are several other direct factor Xa inhibitors
      currently under study. Dabigatran may be considered in AF patients who are
      intolerant to warfarin or unwilling or unable to follow-up with frequent
      laboratory monitoring. Other newer anticoagulant agents also provide us with
      possible suitable alternatives to warfarin, and their clinical use will depend on
      the results from ongoing studies.

PMID- 23160167
TI  - News and views from the literature. Cardiac magnetic resonance imaging.
      Determinants and functional significance of myocardial perfusion reserve in
      severe aortic stenosis.

PMID- 23160168
TI  - Virological responses in chronic hepatitis C patients undergoing prolonged
      therapy with low-dose Peg-IFNalpha-2a.
AB  - BACKGROUND/AIMS: Standard dose therapy with pegylated interferon alpha-2a (Peg
      IFNalpha-2a) and ribavirin is not suitable for all patients because of the side
      effects. This study aims to evaluate the virological responses of low-dose but
      long-course Peg-IFNalpha-2a therapy compared with standard therapy. METHODOLOGY:
      Ninety patients with chronic hepatitis C were divided into three groups according
      to their tolerance to Peg-IFNalpha-2a. The courses of treatment were 96 or 48
      weeks respectively in patients with HCV genotypes 1b or 2a in the 67.5 MUg and 90
      MUg groups, and were 48 or 24 weeks in the 180 MUg groups. Serum HCV RNA was
      quantified to determine RVR, EVR, SVR and ETR. RESULTS: There were no statistical
      differences in HCV RNA load, HCV genotype at the baseline of the three groups
      (p>0.05). The rates of RVR, EVR, SVR and ETR (no significant differences in each
      group), were 63.04%, 82.61%, 71.74% and 85.87% in all 92 patients. Genotype 1b
      (95% CI=11.97-82.89; p=0.0075) and RVR (95% CI=0.12-0.53; p<0.001) were important
      predictors of SVR. CONCLUSIONS: Patients with low-dose but long-course Peg
      IFNalpha-2a therapy had similar virological responses compared to those with
      standard therapy. HCV genotype and RVR were independent predictors of SVR.

PMID- 23160169
TI  - Spontaneous rupture of an umbilical hernia in a cirrhotic patient with ascites A
      case report and review of the literature.
AB  - The authors, report a case of spontaneous rupture of an umbilical hernia in a
      cirrhotic patient with ascites and perform a literature review. Their results and
      the published data suggest that it is preferable to perform elective surgery
      after stabilization of the ascites and the patient's general condition in order
      to prevent complications and mortality. KEY WORDS: Ascites, Hernioplasty,
      Spontaneous hernia rupture.

PMID- 23160170
TI  - In vitro assessment of the bioaccessibility of brominated flame retardants in
      indoor dust using a colon extended model of the human gastrointestinal tract.
AB  - An in vitro colon extended physiologically based extraction test (CEPBET) which
      incorporates human gastrointestinal tract (GIT) parameters (including pH and
      chemistry, solid-to-fluid ratio, mixing and emptying rates) was applied for the
      first time to study the bioaccessibility of brominated flame retardants (BFRs)
      from the 3 main GIT compartments (stomach, small intestine and colon) following
      ingestion of indoor dust. Results revealed the bioaccessibility of gamma-HBCD
      (72%) was less than that for alpha- and beta-isomers (92% and 80% respectively)
      which may be attributed to the lower aqueous solubility of the gamma-isomer (2
      MUg L-1) compared to the alpha- and beta-isomers (45 and 15 MUg L-1
      respectively). No significant change in the enantiomeric fractions of HBCDs was
      observed in any of the studied samples. However, this does not completely exclude
      the possibility of in vivo enantioselective absorption of HBCDs, as the GIT cell
      lining and bacterial flora--which may act enantioselectively--are not included in
      the current CE-PBET model. While TBBP-A was almost completely (94%)
      bioaccessible, BDE-209 was the least (14%) bioaccessible of the studied BFRs.
      Bioaccessibility of tri-hepta BDEs ranged from 32-58%. No decrease in the
      bioaccessibility with increasing level of bromination was observed in the studied
      PBDEs.

PMID- 23160171
TI  - Hybrid density functional-molecular mechanics calculations for core-electron
      binding energies of glycine in water solution.
AB  - We report hybrid density functional theory-molecular mechanics (DFT/MM)
      calculations performed for glycine in water solution at different pH values. In
      this paper, we discuss several aspects of the quantum mechanics-molecular
      mechanics (QM/MM) simulations where the dynamics and spectral binding energy
      shifts are computed sequentially, and where the latter are evaluated over a set
      of configurations generated by molecular or Car-Parrinello dynamics simulations.
      In the used model, core ionization takes place in glycine as a quantum mechanical
      (QM) system modeled with DFT, and the solution is described with expedient force
      fields in a large molecular mechanical (MM) volume of water molecules. The
      contribution to the core electronic binding energy from all interactions within
      and between the two (DFT and MM) parts is accounted for, except charge transfer
      and dispersion. While the obtained results were found to be in qualitative
      agreement with experiment, their precision must be qualified with respect to the
      problem of counter ions, charge transfer and optimal division of QM and MM parts
      of the system. Results are compared to those of a recent study [Ottoson et al.,
      J. Am. Chem. Soc., 2011, 133, 3120].

PMID- 23160172
TI  - Retarded oxygen diffusion in heavily phosphorus-doped Czochralski silicon:
      experiments and first-principles calculations.
AB  - The effect of heavy phosphorus (P) doping on oxygen diffusion in Czochralski (Cz)
      silicon has been experimentally and theoretically investigated. It is
      experimentally found that the oxygen diffusion in heavily P-doped Cz silicon is
      retarded, with a diffusion activation energy which is ~0.12 eV larger than that
      of its lightly P-doped counterpart. First-principles calculations suggest that
      the P-O complexes in the -P-Si-O-Si- configuration can form in heavily P-doped Cz
      silicon, leading to the trapping of interstitial oxygen (O(i)) atoms at the
      twelve equivalent second-nearest neighbors of the P atoms. Furthermore, the
      calculated increase of the oxygen diffusion activation energy, taking account of
      the trapping effect of such P-O complexes, is in accordance with the experimental
      result. This indicates that the retarded oxygen diffusion in the heavily P-doped
      Cz silicon can be ascribed to the trapping of O(i) atoms associated with the
      formation of the aforementioned P-O complexes.

PMID- 23160173
TI  - Non-polarizing broadband multilayer reflectors in fish.
AB  - Dielectric multilayer reflectors that are non-polarizing are an important class
      of optical device and have numerous applications within optical fibres [1],
      dielectric waveguides [2] and LEDs [3]. Here we report analyses of a biological
      non-polarizing optical mechanism found in the broadband guanine-cytoplasm
      "silver" multilayer reflectors of three species of fish. Present in the fish
      stratum argenteum are two populations of birefringent guanine crystal, each with
      their optic axes either parallel to the long axis of the crystal or perpendicular
      to the plane of the crystal. This arrangement neutralizes the polarization of
      reflection due the different interfacial Brewster's angles of each population.
      The fish reflective mechanism is distinct from existing non-polarizing mirror
      designs [4, 5, 6, 7] with the important feature that there is no refractive index
      contrast between the low index layers in the reflector and the external
      environment. It is a mechanism that could be readily manufactured and exploited
      in synthetic optical devices.

PMID- 23160174
TI  - Pillar[5]arenes with an introverted amino group: a hydrogen bonding tuning
      effect.
AB  - Pillar[5]arenes with introverted amino groups were produced through aminolysis. X
      ray analysis demonstrated that the intramolecular hydrogen bonding induced the
      amino group toward the inner space of the cavity. The kinetic studies and
      molecular modelings revealed that the hydrogen bonding also contributed to the
      acceleration of the aminolysis through stabilizing the intermediate.

PMID- 23160175
TI  - Evolutionary effects of translocations in bacterial genomes.
AB  - It has become clear that different genome regions need not evolve uniformly. This
      variation is particularly evident in bacterial genomes with multiple chromosomes,
      in which smaller, secondary chromosomes evolve more rapidly. We previously
      demonstrated that substitution rates and gene dispensability were greater on
      secondary chromosomes in many bacterial genomes. In Vibrio, the secondary
      chromosome is replicated later during the cell cycle, which reduces the effective
      dosage of these genes and hence their expression. More rapid evolution of
      secondary chromosomes may therefore reflect weaker purifying selection on less
      expressed genes. Here, we test this hypothesis by relating substitution rates of
      orthologs shared by multiple Burkholderia genomes, each with three chromosomes,
      to a study of gene expression in genomes differing by a major reciprocal
      translocation. This model predicts that expression should be greatest on
      chromosome 1 (the largest) and least on chromosome 3 (the smallest) and that
      expression should tend to decline within chromosomes from replication origin to
      terminus. Moreover, gene movement to the primary chromosome should associate with
      increased expression, and movement to secondary chromosomes should result in
      reduced expression. Our analysis supports each of these predictions, as
      translocated genes tended to shift expression toward their new chromosome
      neighbors despite inevitable cis-acting regulation of expression. This study
      sheds light on the early dynamics of genomes following rearrangement and
      illustrates how secondary chromosomes in bacteria may become evolutionary test
      beds.

PMID- 23160176
TI  - A tight link between orthologs and bidirectional best hits in bacterial and
      archaeal genomes.
AB  - Orthologous relationships between genes are routinely inferred from bidirectional
      best hits (BBH) in pairwise genome comparisons. However, to our knowledge, it has
      never been quantitatively demonstrated that orthologs form BBH. To test this "BBH
      orthology conjecture," we take advantage of the operon organization of bacterial
      and archaeal genomes and assume that, when two genes in compared genomes are
      flanked by two BBH show statistically significant sequence similarity to one
      another, these genes are bona fide orthologs. Under this assumption, we tested
      whether middle genes in "syntenic orthologous gene triplets" form BBH. We found
      that this was the case in more than 95% of the syntenic gene triplets in all
      genome comparisons. A detailed examination of the exceptions to this pattern,
      including maximum likelihood phylogenetic tree analysis, showed that some of
      these deviations involved artifacts of genome annotation, whereas very small
      fractions represented random assignment of the best hit to one of closely related
      in-paralogs, paralogous displacement in situ, or even less frequent genuine
      violations of the BBH-orthology conjecture caused by acceleration of evolution in
      one of the orthologs. We conclude that, at least in prokaryotes, genes for which
      independent evidence of orthology is available typically form BBH and,
      conversely, BBH can serve as a strong indication of gene orthology.

PMID- 23160177
TI  - Evolutionary rate and duplicability in the Arabidopsis thaliana protein-protein
      interaction network.
AB  - Genes show a bewildering variation in their patterns of molecular evolution, as a
      result of the action of different levels and types of selective forces. The
      factors underlying this variation are, however, still poorly understood. In the
      last decade, the position of proteins in the protein-protein interaction network
      has been put forward as a determinant factor of the evolutionary rate and
      duplicability of their encoding genes. This conclusion, however, has been based
      on the analysis of the limited number of microbes and animals for which
      interactome-level data are available (essentially, Escherichia coli, yeast, worm,
      fly, and humans). Here, we study, for the first time, the relationship between
      the position of proteins in the high-density interactome of a plant (Arabidopsis
      thaliana) and the patterns of molecular evolution of their encoding genes. We
      found that genes whose encoded products act at the center of the network are more
      evolutionarily constrained than those acting at the network periphery. This trend
      remains significant when potential confounding factors (gene expression level and
      breadth, duplicability, function, and length of the encoded products) are
      controlled for. Even though the correlation between centrality measures and rates
      of evolution is generally weak, for some functional categories, it is comparable
      in strength to (or even stronger than) the correlation between evolutionary rates
      and expression levels or breadths. In addition, genes encoding interacting
      proteins in the network evolve at relatively similar rates. Finally, Arabidopsis
      proteins encoded by duplicated genes are more highly connected than those encoded
      by singleton genes. This observation is in agreement with the patterns observed
      in humans, but in contrast with those observed in E. coli, yeast, worm, and fly
      (whose duplicated genes tend to act at the periphery of the network), implying
      that the relationship between duplicability and centrality inverted at least
      twice during eukaryote evolution. Taken together, these results indicate that the
      structure of the A. thaliana network constrains the evolution of its components
      at multiple levels.

PMID- 23160178
TI  - Sphingomyelin synthase 1 activity is regulated by the BCR-ABL oncogene.
AB  - Sphingomyelin synthase (SMS) produces sphingomyelin while consuming ceramide (a
      negative regulator of cell proliferation) and forming diacylglycerol (DAG) (a
      mitogenic factor). Therefore, enhanced SMS activity could favor cell
      proliferation. To examine if dysregulated SMS contributes to leukemogenesis, we
      measured SMS activity in several leukemic cell lines and found that it is highly
      elevated in K562 chronic myelogenous leukemia (CML) cells. The increased SMS in
      K562 cells was caused by the presence of Bcr-abl, a hallmark of CML; stable
      expression of Bcr-abl elevated SMS activity in HL-60 cells while inhibition of
      the tyrosine kinase activity of Bcr-abl with Imatinib mesylate decreased SMS
      activity in K562 cells. The increased SMS activity was the result of up
      regulation of the Sms1 isoform. Inhibition of SMS activity with D609 (a
      pharmacological SMS inhibitor) or down-regulation of SMS1 expression by siRNA
      selectively inhibited the proliferation of Bcr-abl-positive cells. The inhibition
      was associated with an increased production of ceramide and a decreased
      production of DAG, conditions that antagonize cell proliferation. A similar
      change in lipid profile was also observed upon pharmacological inhibition of Bcr
      abl (K526 cells) and siRNA-mediated down-regulation of BCR-ABL (HL-60/Bcr-abl
      cells). These findings indicate that Sms1 is a downstream target of Bcr-abl,
      involved in sustaining cell proliferation of Bcr-abl-positive cells.

PMID- 23160179
TI  - CD36 homolog divergence is responsible for the selectivity of carotenoid species
      migration to the silk gland of the silkworm Bombyx mori.
AB  - Dietary carotenoids are absorbed in the intestine and delivered to various
      tissues by circulating lipoproteins; however, the mechanism underlying selective
      delivery of different carotenoid species to individual tissues remains elusive.
      The products of the Yellow cocoon (C) gene and the Flesh (F) gene of the silkworm
      Bombyx mori determine the selectivity for transport of lutein and beta-carotene,
      respectively, to the silk gland. We previously showed that the C gene encodes
      Cameo2, a CD36 family member, which is thought to function as a transmembrane
      lipoprotein receptor. Here, we elucidated the molecular identity of the F gene
      product by positional cloning, as SCRB15, a paralog of Cameo2 with 26% amino acid
      identity. In the F mutant, SCRB15 mRNA structure was severely disrupted, due to a
      1.4 kb genomic insertion in a coding exon. Transgenic expression of SCRB15 in the
      middle silk gland using the binary GAL4-UAS expression system enhanced selective
      beta-carotene uptake by the middle silk gland, while transgenic expression of
      Cameo2 enhanced selective lutein uptake under the same GAL4 driver. Our findings
      indicate that divergence of genes in the CD36 family determines the selectivity
      of carotenoid species uptake by silk gland tissue and that CD36-homologous
      proteins can discriminate among carotenoid species.

PMID- 23160180
TI  - Genetic variation at the FADS1-FADS2 gene locus influences delta-5 desaturase
      activity and LC-PUFA proportions after fish oil supplement.
AB  - Delta-5 and delta-6 desaturases (D5D and D6D) are key enzymes in endogenous
      synthesis of long-chain PUFAs. In this sample of healthy subjects (n = 310),
      genotypes of single nucleotide polymorphisms (SNPs) rs174537, rs174561, and
      rs3834458 in the FADS1-FADS2 gene cluster were strongly associated with
      proportions of LC-PUFAs and desaturase activities estimated in plasma and
      erythrocytes. Minor allele carriage associated with decreased activities of D5D
      (FADS1) (5.84 * 10(-19) <= P <= 4.5 * 10(-18)) and D6D (FADS2) (6.05 * 10(-8) <=
      P <= 4.20 * 10(-7)) was accompanied by increased substrate and decreased product
      proportions (0.05 <= P <= 2.49 * 10(-16)). The significance of haplotype
      association with D5D activity (P = 2.19 * 10(-17)) was comparable to that of
      single SNPs, but haplotype association with D6D activity (P = 3.39 * 10(-28)) was
      much stronger. In a randomized controlled dietary intervention, increasing
      eicosapentaenoic acid (EPA, 20:5n-3) and docosahexaenoic acid (DHA, 22:6n-3)
      intake significantly increased D5D (P = 4.0 * 10(-9)) and decreased D6D activity
      (P = 9.16 * 10(-6)) after doses of 0.45, 0.9, and 1.8 g/day for six months.
      Interaction of rs174537 genotype with treatment was a determinant of D5D activity
      estimated in plasma (P = 0.05). In conclusion, different sites at the FADS1-FADS2
      locus appear to influence D5D and D6D activity, and rs174537 genotype interacts
      with dietary EPA+DHA to modulate D5D.

PMID- 23160181
TI  - Novel common and rare genetic determinants of paraoxonase activity: FTO,
      SERPINA12, and ITGAL.
AB  - HDL-associated paraoxonase 1 (PON1) activity is associated with cardiovascular
      and other human diseases. As the role of genetic variants outside of the PON gene
      cluster on PON1 activity is unknown, we sought to identify common and rare
      variants in such loci. We typed 33,057 variants on the CVD chip in 1,362 subjects
      to test for their effects on adjusted-PON1 activity. Three novel genes (FTO,
      ITGAL, and SERPINA12) and the PON gene cluster had SNPs associated with PON1
      arylesterase (AREase) activity. These loci were carried forward for rare-variant
      analysis using Exome chip genotypes in an overlapping subset of 1,051 subjects
      using sequence kernel association testing. PON1 (P = 2.24 * 10(-4)), PON3 (P =
      0.022), FTO (P = 0.019), and SERPINA12 (P = 0.039) had both common and rare
      variants associated with PON1 AREase. ITGAL variants were associated with PON1
      activity when using weighted sequence kernel association testing (SKAT) analysis
      (P = 2.63 * 10(-3)). When adjusting for the initial common variants, SERPINA12
      became marginally significant (P = 0.09), whereas all other findings remained
      significant (P < 0.05), suggesting independent rare-variant effects. We present
      novel findings that common and rare variants in FTO, SERPINA12, and ITGAL predict
      PON1 activity. These results further link PON1 to diabetes and inflammation and
      may inform the role of HDL in human disease.

PMID- 23160183
TI  - Coronary disease risk curve of serum creatinine is linear in Turkish men, U
      shaped in women.
AB  - OBJECTIVES: The highest levels of glomerular filtration rate are associated with
      increased coronary heart disease (CHD) risk, an issue we investigated in separate
      sexes in a population prone to metabolic syndrome. RESEARCH METHODS AND
      PROCEDURES: In total, 1948 participants of the Turkish Adult Risk Factor study
      with available creatinine determinations were studied at a mean 3.4 years' follow
      up. Using quartiles of creatinine, risk in Cox models of incident CHD or the
      likelihood of combined prevalent and incident CHD was assessed. RESULTS: Women in
      the lowest creatinine quartile demonstrated the lowest risk profile across
      diverse variables, except showing low high-density lipoprotein cholesterol and
      average apolipoprotein A-I and lipoprotein (a) concentrations implicating
      impaired atheroprotective properties. Whereas serum creatinine in men was not
      significantly associated with 6 proinflammatory variables comprised in linear
      regression analysis, apolipoprotein A-I and lipoprotein (a) were significant
      positive covariates in women, the latter tending to negative association in women
      without metabolic syndrome. In men, the highest (>1.10 mg/dL), compared with the
      lowest, creatinine quartile significantly predicted CHD risk, at 1.85-fold
      relative risks, after adjustment for established risk factors. The risk curve in
      women was U-shaped, the top and bottom quartiles tending to display higher risk
      (odds ratio, 1.28 [95% confidence interval, 0.91-1.80]) compared with the 2
      intermediate quartiles. CONCLUSIONS: Increasing serum creatinine values are
      associated strongly and independently with CHD risk in men but not in women in
      whom the risk curve is U-shaped. The phenomenon of low creatinine levels
      underlies some hitherto unexplained relevant observations, and low measurements
      may be attributed to inassayability secondary to involvement in autoimmune
      activation.

PMID- 23160182
TI  - Metabolic products of soluble epoxide hydrolase are essential for monocyte
      chemotaxis to MCP-1 in vitro and in vivo.
AB  - Monocyte chemoattractant protein-1 (MCP-1)-induced monocyte chemotaxis is a major
      event in inflammatory disease. Our prior studies have demonstrated that MCP-1
      dependent chemotaxis requires release of arachidonic acid (AA) by activated
      cytosolic phospholipase A(2) (cPLA(2)). Here we investigated the involvement of
      AA metabolites in chemotaxis. Neither cyclooxygenase nor lipoxygenase pathways
      were required, whereas pharmacologic inhibitors of both the cytochrome-P450 (CYP)
      and the soluble epoxide hydrolase (sEH) pathways blocked monocyte chemotaxis to
      MCP-1. To verify specificity, we demonstrated that the CYP and sEH products
      epoxyeiscosatrienoic acids (EETs) and dihydroxyeicosatrienoic acids (DHETs),
      respectively, restored chemotaxis in the presence of the inhibitors, indicating
      that sEH-derived products are essential for MCP-1-driven chemotaxis. Importantly,
      DHETs also rescued chemotaxis in cPLA(2)-deficient monocytes and monocytes with
      blocked Erk1/2 activity, because Erk controls cPLA(2) activation. The in vitro
      findings regarding the involvement of CYP/sEH pathways were further validated in
      vivo using two complementary approaches measuring MCP-1-dependent chemotaxis in
      mice. These observations reveal the importance of sEH in MCP-1-regulated monocyte
      chemotaxis and may explain the observed therapeutic value of sEH inhibitors in
      treatment of inflammatory diseases, cardiovascular diseases, pain, and even
      carcinogenesis. Their effectiveness, often attributed to increasing EET levels,
      is probably influenced by the impairment of DHET formation and inhibition of
      chemotaxis.

PMID- 23160184
TI  - A retrospective evaluation of radiotherapy for the treatment of local esophageal
      squamous cell carcinoma recurrence after initial complete surgical resection.
AB  - INTRODUCTION: Our purpose was to assess the efficacy of radiation therapy in the
      treatment of locoregional recurrence of esophageal squamous cell carcinoma
      recurrence after curative resection. METHODS: Patients with local esophageal
      squamous cell carcinoma recurrence who were treated at the Cancer Prevention and
      Treatment Center of Sun Yat-sen University from January 1990 to December 2002 and
      whose initial treatment was complete surgical resection (N = 152) were included.
      Of the 152 patients, 60 patients received treatment with radiation therapy, and
      the others did not receive radiation. None of the included patients received
      chemotherapy or radiotherapy before surgery. The Kaplan-Meier method was used to
      calculate the cumulative survival rate. RESULTS: The median survival time was
      16.0 +/- 2.7 months for those who received radiotherapy versus 6.5 +/- 1.6 months
      for those who did not (P < 0.001). The median survival time was greater (22.3 +/-
      4.0 months) for patients who receive a dosage greater than 50 Gy compared with
      those patients who received a dosage of 50 Gy or less (7.7 +/- 0.3 months; P =
      0.033). The overall 3- and 5-year survival rates were 16.4% and 10.4%,
      respectively. The 1-, 2-, and 3- year recurrence-free survival rates were 56.1 +/
      4.3%, 32.9 +/- 4.1%, and 22.0 +/- 3.7%, respectively. CONCLUSION: Radiotherapy
      may help improve the survival rate in patients with local esophageal squamous
      cell carcinoma recurrence after complete surgical resection who have no history
      of radiotherapy.

PMID- 23160186
TI  - CLL clonal heterogeneity: an ecology of competing subpopulations.

PMID- 23160185
TI  - Anti-diabetic functions of soy isoflavone genistein: mechanisms underlying its
      effects on pancreatic beta-cell function.
AB  - Type 2 diabetes is a result of chronic insulin resistance and loss of functional
      pancreatic beta-cell mass. Strategies to preserve beta-cell mass and a greater
      understanding of the mechanisms underlying beta-cell turnover are needed to
      prevent and treat this devastating disease. Genistein, a naturally occurring soy
      isoflavone, is reported to have numerous health benefits attributed to multiple
      biological functions. Over the past 10 years, numerous studies have demonstrated
      that genistein has anti-diabetic effects, in particular, direct effects on beta
      cell proliferation, glucose-stimulated insulin secretion and protection against
      apoptosis, independent of its functions as an estrogen receptor agonist,
      antioxidant, or tyrosine kinase inhibitor. Effects are structure-specific and not
      common to all flavonoids. While there are limited data on the effects of
      genistein consumption in humans with diabetes, there are a plethora of animal and
      cell-culture studies that demonstrate a direct effect of genistein on beta-cells
      at physiologically relevant concentrations (<10 MUM). The effects appear to
      involve cAMP/PKA signaling and there are some studies that suggest an effect on
      epigenetic regulation of gene expression. This review focuses on the anti
      diabetic effects of genistein in both in vitro and in vivo models and potential
      mechanisms underlying its direct effects on beta-cells.

PMID- 23160187
TI  - The spreading influence of platelet HDACs.

PMID- 23160188
TI  - HIT and run: heparin's unusual immune response.

PMID- 23160189
TI  - The extrinsic origin of the magnetodielectric effect in the double perovskite
      La2NiMnO6.
AB  - A La(2)NiMnO(6) polycrystalline sample prepared by the sol-gel method showed
      monoclinic crystal structure with the P2(1)/n space group and a saturation
      magnetization of 4.63 MU(B)/f.u. at 5 K. Impedance spectroscopy results in the
      temperature range of 10 K < T < 300 K have revealed a distinct conduction process
      at grains and grain boundaries, where the grains followed the variable range
      hopping mechanism and the grain boundaries obeyed Arrhenius thermal activation. A
      negative magnetoresistance of 2.5% was observed at the paramagnetic to
      ferromagnetic transition, and this became temperature independent below the
      magnetic ordering. A marginal positive magnetodielectric (MD) effect that
      followed the dielectric relaxation was observed and its magnitude was found to
      decrease with increase of the frequency. A systematic study on the magnetic field
      induced dielectric properties, dc transport and dc bias effect on the dielectric
      permittivity has revealed the extrinsic origin of the MD effect in the bulk
      sample of La(2)NiMnO(6).

PMID- 23160190
TI  - Graphene synthesis: relationship to applications.
AB  - Graphene is a true wonder material that promises much in a variety of
      applications that include electronic devices, supercapacitors, batteries,
      composites, flexible transparent displays and sensors. This review highlights the
      different methods available for the synthesis of graphene and discusses the
      viability and practicalities of using the materials produced via these methods
      for different graphene-based applications.

PMID- 23160191
TI  - Novel flexible Parylene neural probe with 3D sheath structure for enhancing
      tissue integration.
AB  - A Parylene C neural probe with a three dimensional sheath structure was designed,
      fabricated, and characterized. Multiple platinum (Pt) electrodes for recording
      neural signals were fabricated on both inner and outer surfaces of the sheath
      structure. Thermoforming of Parylene was used to create the three dimensional
      sheath structures from flat surface micromachined microchannels using solid
      microwires as molds. Benchtop electrochemical characterization was performed on
      the thin film Pt electrodes using cyclic voltammetry and electrochemical
      impedance spectroscopy and showed that electrodes possessed low impedances
      suitable for neuronal recordings. A procedure for implantation of the neural
      probe was developed and successfully demonstrated in vitro into an agarose brain
      tissue model. The electrode-lined sheath will be decorated with eluting
      neurotrophic factors to promote in vivo neural tissue ingrowth post-implantation.
      These features will enhance tissue integration and improve recording quality
      towards realizing reliable chronic neural interfaces.

PMID- 23160192
TI  - Human SH2B1 mutations are associated with maladaptive behaviors and obesity.
AB  - Src homology 2 B adapter protein 1 (SH2B1) modulates signaling by a variety of
      ligands that bind to receptor tyrosine kinases or JAK-associated cytokine
      receptors, including leptin, insulin, growth hormone (GH), and nerve growth
      factor (NGF). Targeted deletion of Sh2b1 in mice results in increased food
      intake, obesity, and insulin resistance, with an intermediate phenotype seen in
      heterozygous null mice on a high-fat diet. We identified SH2B1 loss-of-function
      mutations in a large cohort of patients with severe early-onset obesity. Mutation
      carriers exhibited hyperphagia, childhood-onset obesity, disproportionate insulin
      resistance, and reduced final height as adults. Unexpectedly, mutation carriers
      exhibited a spectrum of behavioral abnormalities that were not reported in
      controls, including social isolation and aggression. We conclude that SH2B1 plays
      a critical role in the control of human food intake and body weight and is
      implicated in maladaptive human behavior.

PMID- 23160193
TI  - Mutant huntingtin impairs immune cell migration in Huntington disease.
AB  - In Huntington disease (HD), immune cells are activated before symptoms arise;
      however, it is unclear how the expression of mutant huntingtin (htt) compromises
      the normal functions of immune cells. Here we report that primary microglia from
      early postnatal HD mice were profoundly impaired in their migration to
      chemotactic stimuli, and expression of a mutant htt fragment in microglial cell
      lines was sufficient to reproduce these deficits. Microglia expressing mutant htt
      had a retarded response to a laser-induced brain injury in vivo. Leukocyte
      recruitment was defective upon induction of peritonitis in HD mice at early
      disease stages and was normalized upon genetic deletion of mutant htt in immune
      cells. Migration was also strongly impaired in peripheral immune cells from pre
      manifest human HD patients. Defective actin remodeling in immune cells expressing
      mutant htt likely contributed to their migration deficit. Our results suggest
      that these functional changes may contribute to immune dysfunction and
      neurodegeneration in HD, and may have implications for other polyglutamine
      expansion diseases in which mutant proteins are ubiquitously expressed.

PMID- 23160194
TI  - GSK3beta mediates muscle pathology in myotonic dystrophy.
AB  - Myotonic dystrophy type 1 (DM1) is a complex neuromuscular disease characterized
      by skeletal muscle wasting, weakness, and myotonia. DM1 is caused by the
      accumulation of CUG repeats, which alter the biological activities of RNA-binding
      proteins, including CUG-binding protein 1 (CUGBP1). CUGBP1 is an important
      skeletal muscle translational regulator that is activated by cyclin D3-dependent
      kinase 4 (CDK4). Here we show that mutant CUG repeats suppress Cdk4 signaling by
      increasing the stability and activity of glycogen synthase kinase 3beta
      (GSK3beta). Using a mouse model of DM1 (HSA(LR)), we found that CUG repeats in
      the 3' untranslated region (UTR) of human skeletal actin increase active GSK3beta
      in skeletal muscle of mice, prior to the development of skeletal muscle weakness.
      Inhibition of GSK3beta in both DM1 cell culture and mouse models corrected cyclin
      D3 levels and reduced muscle weakness and myotonia in DM1 mice. Our data predict
      that compounds normalizing GSK3beta activity might be beneficial for improvement
      of muscle function in patients with DM1.

PMID- 23160195
TI  - Extrathymic development of murine T cells after bone marrow transplantation.
AB  - Restoring T cell competence is a significant clinical challenge in patients whose
      thymic function is severely compromised due to age or cytoreductive conditioning.
      Here, we demonstrate in mice that mesenteric LNs (MLNs) support extrathymic T
      cell development in euthymic and athymic recipients of bone marrow
      transplantation (BMT). Furthermore, in aged murine BMT recipients, the
      contribution of the MLNs to the generation of T cells was maintained, while the
      contribution of the thymus was significantly impaired. Thymic impairment resulted
      in a proportional increase in extrathymic-derived T cell progenitors. Extrathymic
      development in athymic recipients generated conventional naive TCRalphabeta T
      cells with a broad Vbeta repertoire and intact functional and proliferative
      potential. Moreover, in the absence of a functional thymus, immunity against
      known pathogens could be augmented using engineered precursor T cells with viral
      specificity. These findings demonstrate the potential of extrathymic T cell
      development for T cell reconstitution in patients with limited thymic function.

PMID- 23160196
TI  - Endothelial Kruppel-like factor 4 protects against atherothrombosis in mice.
AB  - The endothelium regulates vascular homeostasis, and endothelial dysfunction is a
      proximate event in the pathogenesis of atherothrombosis. Stimulation of the
      endothelium with proinflammatory cytokines or exposure to hemodynamic-induced
      disturbed flow leads to a proadhesive and prothrombotic phenotype that promotes
      atherothrombosis. In contrast, exposure to arterial laminar flow induces a gene
      program that confers a largely antiadhesive, antithrombotic effect. The molecular
      basis for this differential effect on endothelial function remains poorly
      understood. While recent insights implicate Kruppel-like factors (KLFs) as
      important regulators of vascular homeostasis, the in vivo role of these factors
      in endothelial biology remains unproven. Here, we show that endothelial KLF4 is
      an essential determinant of atherogenesis and thrombosis. Using in vivo EC
      specific KLF4 overexpression and knockdown murine models, we found that KLF4
      induced an antiadhesive, antithrombotic state. Mechanistically, we demonstrated
      that KLF4 differentially regulated pertinent endothelial targets via competition
      for the coactivator p300. These observations provide cogent evidence implicating
      endothelial KLFs as essential in vivo regulators of vascular function in the
      adult animal.

PMID- 23160197
TI  - B cell exchange across the blood-brain barrier in multiple sclerosis.
AB  - In multiple sclerosis (MS) pathogenic B cells likely act on both sides of the
      blood-brain barrier (BBB). However, it is unclear whether antigen-experienced B
      cells are shared between the CNS and the peripheral blood (PB) compartments. We
      applied deep repertoire sequencing of IgG heavy chain variable region genes (IgG
      VH) in paired cerebrospinal fluid and PB samples from patients with MS and other
      neurological diseases to identify related B cells that are common to both
      compartments. For the first time to our knowledge, we found that a restricted
      pool of clonally related B cells participated in robust bidirectional exchange
      across the BBB. Some clusters of related IgG-VH appeared to have undergone active
      diversification primarily in the CNS, while others have undergone active
      diversification in the periphery or in both compartments in parallel. B cells are
      strong candidates for autoimmune effector cells in MS, and these findings suggest
      that CNS-directed autoimmunity may be triggered and supported on both sides of
      the BBB. These data also provide a powerful approach to identify and monitor B
      cells in the PB that correspond to clonally amplified populations in the CNS in
      MS and other inflammatory states.

PMID- 23160198
TI  - HIV-1 infection-induced apoptotic microparticles inhibit human DCs via CD44.
AB  - Acute HIV-1 infection results in dysregulated immunity, which contributes to poor
      control of viral infection. DCs are key regulators of both adaptive and innate
      immune responses needed for controlling HIV-1, and we surmised that factors
      elicited during acute HIV-1 infection might impede DC function. We derived
      immature DCs from healthy donor peripheral blood monocytes and treated them with
      plasma from uninfected control donors and donors with acute HIV-1 infections. We
      found that the plasma from patients with HIV specifically inhibited DC function.
      This suppression was mediated by elevated apoptotic microparticles derived from
      dying cells during acute HIV-1 infection. Apoptotic microparticles bound to and
      inhibited DCs through the hyaluronate receptor CD44. These data suggest that
      targeting this CD44-mediated inhibition by apoptotic microparticles could be a
      novel strategy to potentiate DC activation of HIV-specific immunity.

PMID- 23160202
TI  - When what you hear influences when you see: listening to an auditory rhythm
      influences the temporal allocation of visual attention.
AB  - The three experiments reported here demonstrated a cross-modal influence of an
      auditory rhythm on the temporal allocation of visual attention. In Experiment 1,
      participants moved their eyes to a test dot with a temporal onset that was either
      synchronous or asynchronous with a preceding auditory rhythm. Saccadic latencies
      were faster for the synchronous condition than for the asynchronous conditions.
      In Experiment 2, the effect was replicated in a condition in which the auditory
      context stopped prior to the onset of the test dot, and the effect did not occur
      in a condition in which auditory tones were presented at irregular intervals.
      Experiment 3 replicated the effect using an accuracy measure within a nontimed
      visual task. Together, the experiments' findings support a general entrainment
      perspective on attention to events over time.

PMID- 23160199
TI  - Viperin restricts chikungunya virus replication and pathology.
AB  - Chikungunya virus (CHIKV) is a mosquito-borne arthralgia arbovirus that is
      reemergent in sub-Saharan Africa and Southeast Asia. CHIKV infection has been
      shown to be self-limiting, but the molecular mechanisms of the innate immune
      response that control CHIKV replication remain undefined. Here, longitudinal
      transcriptional analyses of PBMCs from a cohort of CHIKV-infected patients
      revealed that type I IFNs controlled CHIKV infection via RSAD2 (which encodes
      viperin), an enigmatic multifunctional IFN-stimulated gene (ISG). Viperin was
      highly induced in monocytes, the major target cell of CHIKV in blood. Anti-CHIKV
      functions of viperin were dependent on its localization in the ER, and the N
      terminal amphipathic alpha-helical domain was crucial for its antiviral activity
      in controlling CHIKV replication. Furthermore, mice lacking Rsad2 had higher
      viremia and severe joint inflammation compared with wild-type mice. Our data
      demonstrate that viperin is a critical antiviral host protein that controls CHIKV
      infection and provide a preclinical basis for the design of effective control
      strategies against CHIKV and other reemerging arthrogenic alphaviruses.

PMID- 23160203
TI  - 9/11, Act II: a fine-grained analysis of regional variations in traffic
      fatalities in the aftermath of the terrorist attacks.
AB  - Terrorists can strike twice--first, by directly killing people, and second,
      through dangerous behaviors induced by fear in people's minds. Previous research
      identified a substantial increase in U.S. traffic fatalities subsequent to the
      September 11 terrorist attacks, which were accounted for as due to a substitution
      of driving for flying, induced by fear of dread risks. Here, we show that this
      increase in fatalities varied widely by region, a fact that was best explained by
      regional variations in increased driving. Two factors, in turn, explained these
      variations in increased driving. The weaker factor was proximity to New York
      City, where stress reactions to the attacks were previously shown to be greatest.
      The stronger factor was driving opportunity, which was operationalized both as
      number of highway miles and as number of car registrations per inhabitant. Thus,
      terrorists' second strike exploited both fear of dread risks and, paradoxically,
      an environmental structure conducive to generating increased driving, which
      ultimately increased fatalities.

PMID- 23160200
TI  - C/EBPgamma deregulation results in differentiation arrest in acute myeloid
      leukemia.
AB  - C/EBPs are a family of transcription factors that regulate growth control and
      differentiation of various tissues. We found that C/EBPgamma is highly
      upregulated in a subset of acute myeloid leukemia (AML) samples characterized by
      C/EBPalpha hypermethylation/silencing. Similarly, C/EBPgamma was upregulated in
      murine hematopoietic stem/progenitor cells lacking C/EBPalpha, as C/EBPalpha
      mediates C/EBPgamma suppression. Studies in myeloid cells demonstrated that CEBPG
      overexpression blocked neutrophilic differentiation. Further, downregulation of
      Cebpg in murine Cebpa-deficient stem/progenitor cells or in human CEBPA-silenced
      AML samples restored granulocytic differentiation. In addition, treatment of
      these leukemias with demethylating agents restored the C/EBPalpha-C/EBPgamma
      balance and upregulated the expression of myeloid differentiation markers. Our
      results indicate that C/EBPgamma mediates the myeloid differentiation arrest
      induced by C/EBPalpha deficiency and that targeting the C/EBPalpha-C/EBPgamma
      axis rescues neutrophilic differentiation in this unique subset of AMLs.

PMID- 23160204
TI  - Affective signals of threat increase perceived proximity.
AB  - Do stimuli appear to be closer when they are more threatening? We tested people's
      perceptions of distance to stimuli that they felt were threatening relative to
      perceptions of stimuli they felt were disgusting or neutral. Two studies
      demonstrated that stimuli that emitted affective signals of threat (e.g., an
      aggressive male student) were seen as physically closer than stimuli that emitted
      affective signals of disgust (e.g., a repulsive male student) or no affective
      signal. Even after controlling for the direct effects of physiological arousal,
      object familiarity, and intensity of the negative emotional reaction, we found
      that threatening stimuli appeared to be physically closer than did disgusting
      ones (Study 2). These findings highlight the links among biased perception,
      action regulation, and successful navigation of the environment.

PMID- 23160205
TI  - Immunology beats cancer: a blueprint for successful translation.
AB  - Immunology offers an unprecedented opportunity for the science-driven development
      of therapeutics. The successes of antibodies to the immunomodulatory receptor
      CTLA-4 and blockade of the immunoinhibitory receptor PD-1 in cancer
      immunotherapy, from gene discovery to patient benefit, have created a paradigm
      for driving such endeavors.

PMID- 23160206
TI  - HOIL and water: the two faces of HOIL-1 deficiency.

PMID- 23160207
TI  - Nonclassical NK cell education.

PMID- 23160208
TI  - Innate sensing of bacterial cyclic dinucleotides: more than just STING.

PMID- 23160209
TI  - A less-canonical, canonical NF-kappaB pathway in DCs.

PMID- 23160210
TI  - IL-2 and IL-15 signaling complexes: different but the same.

PMID- 23160219
TI  - Effect of fluoxetine and adenosine receptor NECA agonist on G alpha q/11 protein
      of C6 glioma cells.
AB  - OBJECTIVES: Trimeric G-proteins play a crucial role in the transmembrane
      signalling to intracellular pathways via effector phospholipase C (1,4,5 IP3) or
      adenylylcyclase (cAMP). G-protein modulation is considered to participate in the
      antidepressant mode of action by neurotransmitter G-protein coupled receptors
      (GPCR). Adenosine is naturally occured nucleoside and adenosine receptor belongs
      to GPCR family. Properties and functions of ubiquitous adenosine receptor were
      described with number of agonists and antagonists. METHODS: In C6 glioma cells,
      we studied acute administration of SSRI antidepressants - fluoxetine, sertraline
      and citalopram. We used immunochemical estimation (ELISA) of the main types of G
      protein alpha subunits from isolated membranes of C6 glioma cells. We also
      estimated effect of NECA agonist on fluoxetine induced signalling via 1,4,5 IP3
      and its levels. RESULTS: Results show involvement of the antidepressant drugs in
      the C6 glioma signal transduction cascades and their modulation in dependence on
      the antidepressant of SSRI type. We measured main G alpha protein profiles after
      fluoxetine, sertraline and citalopram administration. We found significant
      changes as following: decreased G alpha Gq/11 for fluoxetine, low G alpha s for
      sertraline and both high G alpha q/11 and high G alpha s for citalopram.
      Furthermore the NECA (5'-N-ethylcarboxamido- adenosine) agonist of adenosine
      receptor alone evoked high decrease of G alpha q/11 levels. Whereas fluoxetine
      influenced G alpha q/11 decline was abolished by NECA in concentration manner,
      especially at 10-8 and 10-9 M concentrations. These results support abolishion
      NECA effect on fluoxetin influenced 1,4,5 IP3 signalling via PLC. CONCLUSION:
      Main G alpha profiles are dependent on SSRI type antidepressant. Abolishing both
      fluoxetine evoked G alpha q/11 and and 1,4,5 IP3 signalling can indicate parallel
      interference between G-protein coupled receptors (GPCR) and the cell response.
      Presented data are first findings about adenosine receptor interaction with
      fluoxetine signalling. Thus in vitro studies contribute to the clarification of
      the molecular basis of antidepressant action.

PMID- 23160218
TI  - Caspase-1 deficiency in mice reduces intestinal triglyceride absorption and
      hepatic triglyceride secretion.
AB  - Caspase-1 is known to activate the proinflammatory cytokines IL-1beta and IL-18.
      Additionally, it can cleave other substrates, including proteins involved in
      metabolism. Recently, we showed that caspase-1 deficiency in mice strongly
      reduces high-fat diet-induced weight gain, at least partly caused by an increased
      energy production. Increased feces secretion by caspase-1-deficient mice suggests
      that lipid malabsorption possibly further reduces adipose tissue mass. In this
      study we investigated whether caspase-1 plays a role in triglyceride-(TG)-rich
      lipoprotein metabolism using caspase-1-deficient and wild-type mice. Caspase-1
      deficiency reduced the postprandial TG response to an oral lipid load, whereas TG
      derived fatty acid (FA) uptake by peripheral tissues was not affected,
      demonstrated by unaltered kinetics of [(3)H]TG-labeled very low-density
      lipoprotein (VLDL)-like emulsion particles. An oral gavage of [(3)H]TG-containing
      olive oil revealed that caspase-1 deficiency reduced TG absorption and subsequent
      uptake of TG-derived FA in liver, muscle, and adipose tissue. Similarly, despite
      an elevated hepatic TG content, caspase-1 deficiency reduced hepatic VLDL-TG
      production. Intestinal and hepatic gene expression analysis revealed that caspase
      1 deficiency did not affect FA oxidation or FA uptake but rather reduced
      intracellular FA transport, thereby limiting lipid availability for the assembly
      and secretion of TG-rich lipoproteins. The current study reveals a novel function
      for caspase-1, or caspase-1-cleaved substrates, in controlling intestinal TG
      absorption and hepatic TG secretion.

PMID- 23160220
TI  - Effect of tyrosine hydroxylase gene silencing in CD4+ T lymphocytes on
      differentiation and function of helper T cells.
AB  - OBJECTIVES: We explored effect of gene silencing of tyrosine hydroxylase (TH), a
      rate-limiting enzyme for synthesis of catecholamines (CAs), in CD4+ T cells on
      differentiation and function of helper T (Th) cells to provide more evidence for
      functional significance of lymphocyte-derived CAs. METHODS: CD4+ T lymphocytes
      were isolated and purified from the mesenteric lymph nodes of mice. Recombinant
      TH miRNA expression vector (pcDNA6.2-GW/EmGFPmiR-TH) was constructed and
      transfected into concanavalin A (Con A)-activated CD4+ T lymphocytes using
      nucleofection technology. After incubated for 48 h, these cells were detected for
      TH gene and protein expression and CA content. Simultaneously, percentage of
      interferon-gamma (IFN-gamma)- and interleukin-4 (IL-4)-producing cells and levels
      of IL-2, IFN-gamma, tumor necrosis factor (TNF), IL-4 and IL-5 in culture
      supernatants of Con A-stimulated CD4+ T cells were examined by flow cytometric
      analysis. RESULTS: CD4+ T lymphocytes with TH RNAi expressed less TH mRNA and
      protein and synthesized less CAs including norepinephrine, epinephrine and
      dopamine than control cells with mock transfection. The silencing of TH gene in
      CD4+ T lymphocytes reduced percentage of IL-4-producing cells and elevated ratio
      of IFN-gamma-producing cells to IL-4-producing cells, although it did not alter
      proportion of IFN-gamma-producing cells. The Th1 cytokines, IL-2, IFN-gamma and
      TNF, were increased, but the Th2 cytokines, IL-4 and IL-5, were decreased in the
      culture supernatants of Con A-stimulated CD4+ T lymphocytes that were transfected
      with TH miRNA. CONCLUSION: TH gene silencing attenuates TH expression and CA
      synthesis in CD4+ T lymphocytes and promotes polarization of differentiation and
      function towards Th1 cells.

PMID- 23160217
TI  - Re(de)fining the dendritic cell lineage.
AB  - Dendritic cells (DCs) are essential mediators of innate and adaptive immune
      responses. Study of these critical cells has been complicated by their similarity
      to other hematopoietic lineages, particularly monocytes and macrophages. Progress
      has been made in three critical areas of DC biology: the characterization of
      lineage-restricted progenitors in the bone marrow, the identification of
      cytokines and transcription factors required during differentiation, and the
      development of genetic tools for the visualization and depletion of DCs in vivo.
      Collectively, these advances have clarified the nature of the DC lineage and have
      provided novel insights into their function during health and disease.

PMID- 23160221
TI  - Effects of estradiol and progesterone on gonadotropin LHbeta- and FSHbeta-subunit
      promoter activities in gonadotroph LbetaT2 cells.
AB  - OBJECTIVES: Sex steroid hormones play roles in the regulation of pituitary
      hormone synthesis and secretion. Here we investigated the role of estradiol (E2)
      and progesterone (P4) on pituitary gonadotropin luteinizing hormone (LH)beta- and
      follicle stimulating hormone (FSH)beta-transcriptional activity in a single
      colony of gonadotroph LbetaT2 cells. METHODS: Pituitary gonadotroph cell line,
      LbetaT2 cells were used in this study. Cells were transfected with LHbeta- or
      FSHbeta-subunit promoter region-linked luciferase vector, and stimulated with
      gonadotropin-releasing hormone (GnRH) in the presence or absence of sex steroids.
      Transcriptional activity for LHbeta- and FSHbeta-subunit were determined by
      luciferase assay. Effects of sex steroids on cell proliferation was also
      determined by measurement of 5-bromoe-2'-deoxyuridine (BrdU) incorporation.
      RESULTS: The basal promoter activity of the LHbeta subunit was not modulated by
      10 nM E2, but gonadotropin releasing hormone (GnRH)-induced LHbeta promoter
      activity was significantly increased by the same concentration of E2. Similarly,
      although the basal FSHbeta promoter was not modulated by 10 nM E2, GnRH-induced
      FSHbeta promoters were significantly potentiated in the presence of E2. One
      micromole E2 modulated neither basal nor GnRH-induced LHbeta and FSHbeta
      promoters. On the other hand, basal LHbeta promoter activity was enhanced by 1 uM
      P4, but the stimulatory response of GnRH on LHbeta promoters was significantly
      inhibited in the presence of 1 uM P4. Similar to LHbeta promoters, the basal
      activity of the FSHbeta promoter was increased by 1 uM P4; however, the response
      to GnRH was not modulated in the presence of P4. Ten micromoles P4 modified
      neither basal nor GnRH-induced promoter activity for LHbeta and FSHbeta. E2 had
      no antagonistic effect on P4-induced basal promoter activities of LHbeta or
      FSHbeta. A cell proliferation assay showed that neither E2 nor P4 modulated the
      growth of LbetaT2 cells, even in the presence or absence of GnRH. CONCLUSION:
      These observations suggest that both E2 and P4 uniquely modulate basal and GnRH
      stimulated gonadotropin promoters without affecting cell growth.

PMID- 23160222
TI  - Evolutional background of dominance/submissivity in sex and bondage: the two
      strategies?
AB  - OBJECTIVES: We theorize that sexual arousal by dominance and submission may be
      connected to a reproduction strategy respecting a reached social dominance rank
      (a common reproduction strategy in socially living mammals), while the preference
      for "bondage" may be derived from an opportunistic strategy when being unable to
      compete for hierarchic rank (an alternative reproductive strategy that co-occurs
      frequently with the above-named main strategy). The answers to questions dealing
      with hierarchy in character should correlate exclusively with sexual arousal
      connected to any kind of expression of a hierarchy, but not with bondage. DESIGN
      AND SETTINGS: The data were obtained from young adults (157 males and 183 females
      aged 18-20, with mean 18.4 years) via questionnaires. RESULTS: Seven out of eight
      questions dealing with hierarchy correlated with sexual arousal by dominance and
      submission in men (Spearman's r=0.169-0.313; p<0.05 - p<0.001), two questions
      correlated with sexual arousal by dominance and submission in women (Spearman's
      r=0.32-0.166, p<0.001, p<0.05).  THE MAIN FINDINGS: The questions dealing with
      hierarchy correlated with sexual arousal by dominance and submission while no
      answers correlated with bondage, neither in men nor in women. CONCLUSION: The
      preference for sexual arousal by dominance and submission may be connected to
      strategy respecting rank, while the preference for "bondage" may be derived from
      an opportunistic strategy that may be essential for possible partner problems
      solution. From the evolutionary biology point of view, these patterns of
      sadomasochistic sex appear as adaptive rather than as pathology.

PMID- 23160223
TI  - Extremely large vulvar fibroma in a 15-year-old girl.
AB  - BACKGROUND: Fibromas and fibromyomas belong to the most common solid vulvar
      tumors. Their cause remains unknown. CASE: A 15-year-old girl arrived at our
      department for extirpation of a large pendulous vulval fibroma. For three years
      she had observed a gradually enlarging structure protruding from her external
      genitals. After a preoperative CT examination the tumor was extirpated with a
      histological diagnosis of benign soft fibroma. CONCLUSION: Our report describes a
      therapeutic management of a large vulval fibroma in a young girl. The extended
      time from first symptoms to final treatment deserves reflection.

PMID- 23160224
TI  - Hippocampal asymmetry in expression of catecholamine synthesizing enzyme and
      transporters in socially isolated rats.
AB  - OBJECTIVES: Right-left asymmetry of human brain function has been known for a
      century. Brain asymmetry and lateralization has been observed at the
      neurochemical level. At the neurochemical level, it is important to further
      correlate changes in monoaminergic activity with the synthesis and reuptake of
      these monoamines. The aim of the present study was to analyze the effect of
      social isolation on catecholamine stores as well as on the regulation of
      catecholamine synthesis and uptake in the right and left hippocampus. METHODS: We
      examined changes in protein levels of dopamine-beta-hydroxylase (DBH),
      norepinephrine transporter (NET) and vesicular monoamine transporter 2 (VMAT 2)
      in the right and left hippocampus of socially isolated adult male rats during 12
      weeks by Western blot analysis. RESULTS: Chronic isolation stress reduced
      norepinephrine content in the right hippocampus. No changes were observed in
      protein levels of DBH and NET in the right hippocampus, whereas expression of
      this norepinephrine synthetizing enzyme and transporter were elevated in the left
      hippocampus. On the other hand, chronic isolation stress caused reduction of
      VMAT2 protein in the right hippocampus. CONCLUSION: Our results reveale not only
      the lateralization of stress regulatory system but they also show that long-term
      isolation stress produces right-left asymmetry of the hippocampus norepinephrine,
      different regulation of the catecholamines synthesis and reuptake.

PMID- 23160225
TI  - Hypnic headache - a rare primary headache disorder with very good response to
      indomethacin.
AB  - Hypnic headache (HH) is considered as a disorder of the circadian rhythm, mostly
      affecting the elderly and generally considered a benign disorder, but the
      pathophysiology of hypnic hedache remains unclear. Various treatments have been
      suggested for hypnic headache, especially lithium and indomethacin. We report the
      case of HH fulfilling The International Classification Headache Disorders, 2nd
      edition criteria (ICHD-II). A 64-year-old woman, who suffered from dull headaches
      strictly during the night for a period of 5 months. Attacks of headache lasted
      from 30 to 150 minutes, with a frequency usually 4 times per week. The patient
      was started on indomethacin 50 mg twice a day (BID). From day 25 on she was free
      of hypnic headache. On day 31 we tapered the daily dose of indomethacin to 50mg
      at bedtime, the patient was still without headache. On day 60 the treatment was
      stopped. 30 months after day 60, the patient was still headache free. We reported
      the first Czech patient with HH with very good therapeutic response to
      indomethacin. The effect of therapy with indomethacin 50mg BID was very fast and
      stable.

PMID- 23160226
TI  - Hypothalamic dysfunctions as a late consequence of surgical opening of the lamina
      terminalis. A controversial hypothesis.
AB  - BACKGROUND: Opening of the lamina terminalis is often used in surgery of the
      optico-chiasmatic region. Consequently, alteration of cerebral-spinal fluid (CSF)
      dynamics can occur after this manoeuvre, thus potentially translating into
      clinical complications. Herein, we describe 2 cases in which clinically relevant
      hypothalamic dysfunctions developed after few days opening of the lamina
      terminalis both patients showed mild to moderate preoperative hydrocephalus which
      improved postoperatively. CASES DESCRIPTION: In a patient with ruptured aneurysm
      of the basilar bifurcation, opening of the lamina terminalis was performed prior
      to acute-stage clipping. On postoperative day 7th, the patient developed
      significant subdural hygroma, mild disturbances of consciousness and increase of
      ADH concentration. These clinical features resolved only following subdural
      hygroma drainage and ventricular-peritoneal shunting. One previously operated
      patient in whom the lamina terminalis had been opened to remove a sizeable
      parasellar tumour showed a similar post-operative course. In this patient, sole
      subdural hygroma drainage was not an effective treatment, and the patient died
      subsequently for complications related to long-standing, though mild,
      hypothalamic dysfunction. CONCLUSIONS: Our experience may suggest that
      hypothalamic dysfunctions should be reminded as a possible, although rare,
      complication following the opening of the lamina terminalis. This clinical
      condition, if not properly managed, may contribute to trigger severe life
      threatening complications.

PMID- 23160227
TI  - Idiopathic intracranial hypertension: a unifying neuroendocrine hypothesis
      through the adrenal-brain axis.
AB  - The clinical syndrome idiopathic intracranial hypertension (IIH), also termed
      pseudotumor cerebri, consists of symptoms of headache, nausea, vomiting and
      visual field defects in combination with findings of papilledema.  IIH is more
      commonly seen in overweight women where the rise in intracranial pressure is
      putatively a consequence of an endocrine-based disturbance of electrolytes. Less
      frequently, it can also occur in men and in the pediatric age group. Associated
      risk factors include primary and secondary aldosteronism, pregnancy, recombinant
      growth hormone (r-GH) therapy, oral contraceptives, obesity, vitamin A
      intoxication or deficiency, Addison disease, corticosteroid therapy or acute
      withdrawal of steroid therapy and Cushing disease. Herein, we review the
      association between these conditions and IIH working toward its having a unifying
      neuroendocrine hypothesis.

PMID- 23160228
TI  - Influence of SYSADOA group chemicals on progression of human knee joint
      osteoarthritis: new objective evaluation method - measuring of rheological
      properties in vivo.
AB  - OBJECTIVES: This study seeks to demonstrate the influence of pharmacological
      substances from the SYSADOA group on the progression of osteoarthritis in the
      human knee. The quantification methods were direct measurement of the rheological
      properties of the knee joints in vivo and standard WOMAC index questionnaires.
      MATERIALS AND METHODS: The drugs were administered orally to 34 probands with
      second degree gonarthrosis for 13 weeks. The untreated control group consisted of
      10 probands. The rheological properties of the joints were determined by a
      biorheometer, and subjective assessment of the knees by patients (WOMAC) before
      and after medication, and for a further 13 weeks. Changes in the calculated
      parameters over time were compared. RESULTS: During the audited perioda slight
      deterioration in all of the parameters was observed in the untreated group. The
      treated group, however, improved in all the parameters and some indicators showed
      statistically significant differences. The positive effects of the SYSADOA
      persisted for 3 months after the end of treatments. Partial correlation was found
      between the results of the WOMAC questionnaire and the rheological measurements.
      CONCLUSIONS: This study shows the positive effects of the preparation on
      arthritic changes in the knee joint, but due to the large variance of the
      collected data, this conclusion is on the borderline of statistical significance.
      The method of measuring the rheological properties of the joints is suitable for
      evaluating the progression of OA.

PMID- 23160229
TI  - Natalizumab in the treatment of pediatric multiple sclerosis.
AB  - Pediatric cerebrospinal multiple sclerosis (MS) constitutes about 2-5% of all MS
      cases. The International Pediatric MS Study Group (IPMSSG) applies diagnostic
      criteria for adults to MS in childhood and adolescence. Recent publications
      highlight an increasing number of MS in children resistant to the first-line
      treatment, i.e. disease modifying therapy (DMT). Furthermore, the number of
      published case studies on children with highly active MS treated with natalizumab
      also rises, whereas long-term risks as well as therapeutic potential of this
      therapy in pediatric population have been at the centre of attention. This paper
      presents a group of 5 children in whom natalizumab was selected to manage highly
      active disease or resistance to conventional MS treatment and provided very good
      clinical as well as MRI results.

PMID- 23160230
TI  - Pituitary abscess presenting two years after the diagnosis of a pituitary lesion
      in a patient with panhypopituitarism.
AB  - Pituitary abscess is a rare condition. Here, we present the case of a young male
      patient who was initially found to have a pituitary lesion following the
      diagnosis of panhypopituitarism. Two years later, he presented with severe
      headache and was subsequently diagnosed intraoperatively with pituitary abscess.
      At a follow-up of 6 years after surgery, the patient was continuing to do very
      well. We discuss the differential diagnosis and demonstrate the evolution of the
      pituitary lesion on magnetic resonance imaging at four different time points: at
      the time of the detection of the initial lesion; two years later at the time of
      the diagnosis of the pituitary abscess; at 7 weeks post operatively; and finally
      after six years from the pituitary surgery.

PMID- 23160231
TI  - Prodromes, precipitants, and risk factors for relapse in bipolar disorder.
AB  - OBJECTIVE: The purpose of this qualitative review is to examine prodromes,
      precipitants, and risk factors for repeated episodes of mania and depression in
      bipolar disorder. METHODS: PubMed, EMBASE, and PsychInfo were searched for
      "bipolar disorder" in conjunction with: "prodromes", "triggers", and "life change
      events". RESULTS: Phenomenology and prevalence of prodromes, precipitants, and
      risk factors are described, and their therapeutic implications are outlined.
      CONCLUSIONS: Most patients with bipolar disorder are able to recognize their
      prodromes. This ability depends largely on insight. Psychoeducation focused on
      improving various aspects of insight, including treatment adherence, reduces
      incidence of relapses in bipolar disorder.

PMID- 23160232
TI  - Reduced posterior cingulate glutamate measured by magnetic resonance spectroscopy
      in hyperthyroidism.
AB  - OBJECTIVES: Patients with hyperthyroidism frequently have neuropsychiatric
      complaints such as lack of concentration, poor performance in memory, depression,
      anxiety and mania. These symptoms suggest the dysfunction of brain. However, the
      underlying process of this dysfunction is not well understood. At the same time,
      glutamatergic system has been considered important in neuropsychiatric process by
      recent studies. Thus, this study is to investigate the change of glutamate
      concentration in patients with hyperthyroidism using proton magnetic resonance
      spectroscopy. METHODS: Fifteen untreated patients with hyperthyroidism and
      fifteen age- and gender- matched controls participated in the study. The region
      of the posterior cingulate cortex was examined by magnetic resonance spectroscopy
      with a technique referred as TE-averaged PRESS at 3T field strength. The
      concentrations of N-Acetylaspartate, creatine, choline and glutamate were
      assessed using jMRUI v4.0 software. RESULTS: Hyperthyroid patients, compared with
      controls, showed a decrease of glutamate concentration (P<0.047) and
      glutamate/creatine ratios (P<0.009) in the posterior cingulate cortex. The
      decrease of choline concentration (P<0.004) and choline/creatine ratios (P<0.012)
      were also discovered. No significant difference was found in the concentrations
      of N-Acetylaspartate or creatine between patients and controls. CONCLUSION:
      Concentration of glutamate decreased in the region of posterior cingulate cortex
      in patients with hyperthyroidism. This reduction indicated a possible involvement
      of glutamate in the brain dysfunction in hyperthyroidism.

PMID- 23160233
TI  - Resistin levels in women with ischemic stroke.
AB  - OBJECTIVES: Resistin may be an independent inflammatory marker of
      atherosclerosis. Therefore, its circulating level might be important prognostic
      factor of cardiovascular disease in humans. We aimed in this study to assess
      plasma resistin concentration in Polish women with acute ischemic stroke, who
      additionally suffer from chronic diseases: diabetes, hypertension and/or obesity.
      The changes of resistin levels after 10 days from the onset of stroke and
      possible associations between resistin and pro-inflammatory cytokine TNFalpha
      were also evaluated. MATERIAL AND METHODS: Material consisted of 41 women with
      ischemic stroke (aged 60-85 years) and 64 controls (aged 60-85 years).
      Circulating resistin and TNFalpha concentrations were measured using ELISA. Blood
      was taken twice in the stroke group, in the first and tenth day from the onset of
      clinical symptoms, and only once in the controls. Clinical and biochemical data
      (blood pressure, weight, height, glucose, insulin, lipid profile) were collected.
      RESULTS: Higher concentrations of resistin and TNFalpha were observed in ischemic
      stroke patients at the first day comparing to the controls. Second evaluation
      after 10 days in comparison with the first measurement revealed significantly
      higher TNFalpha levels and non-significant lower values of resistin. Resistin
      positively correlated with TNFalpha and stroke severity. CONCLUSIONS: Changes in
      resistin and TNFalpha concentrations were observed in the course of stroke.
      Further investigations are required to assess the implication of these findings.
      Higher resistin concentration might be associated with worse neurological
      deficits.

PMID- 23160234
TI  - Generation of monodispersed microdroplets by temperature controlled bubble
      condensation processes.
AB  - This work introduces a microfluidic method for the generation of monodispersed
      microdroplets by using temperature controlled bubble condensation processes. In
      this method, the dispersed phase is first vaporized in the feeding pipe and
      ruptured to monodispersed bubbles in a coflowing stream. These bubbles are then
      condensed in the downstream pipe, where monodispersed microdroplets are obtained.
      This method ensures the narrow distribution of droplet diameters and prepares
      microdroplets less than 200 MUm in sub-millimeter fluidic devices.

PMID- 23160235
TI  - Pyrazine excited states revisited using the extended multi-state complete active
      space second-order perturbation method.
AB  - We demonstrate that the recently developed extended multi-state complete active
      space second-order perturbation theory (XMS-CASPT2) [Shiozaki et al., J. Chem.
      Phys., 2011, 135, 081106] provides qualitatively correct potential energy
      surfaces for low-lying excited singlet states of pyrazine, while the potential
      energy surfaces of the standard MS-CASPT2 methods are ill-behaved near the
      crossing point of two reference potential energy surfaces. The XMS-CASPT2 method
      is based on the extended multi-configuration quasi-degenerate perturbation theory
      proposed earlier by Granovsky [J. Chem. Phys., 2011, 134, 214113]. We show that
      the conical intersection at the XMS-CASPT2 level can be described without
      artifacts if the entire method is invariant with respect to any unitary rotations
      of the reference functions. The photoabsorption spectra of the 1(1)B(3u) and
      1(1)B(2u) states of pyrazine are simulated, based on a vibronic-coupling model
      Hamiltonian. The XMS-CASPT2 spectrum of the 1(1)B(3u) band is found to be
      comparable to the one computed by a more expensive multireference configuration
      interaction (MRCI) method, while the XMS-CASPT2 simulation of the 1(1)B(2u) band
      is slightly inferior to the MRCI one.

PMID- 23160236
TI  - Multifunctional in vivo vascular imaging using near-infrared II fluorescence.
AB  - In vivo real-time epifluorescence imaging of mouse hind limb vasculatures in the
      second near-infrared region (NIR-II) is performed using single-walled carbon
      nanotubes as fluorophores. Both high spatial (~30 MUm) and temporal (<200 ms per
      frame) resolution for small-vessel imaging are achieved at 1-3 mm deep in the
      hind limb owing to the beneficial NIR-II optical window that affords deep
      anatomical penetration and low scattering. This spatial resolution is
      unattainable by traditional NIR imaging (NIR-I) or microscopic computed
      tomography, and the temporal resolution far exceeds scanning microscopic imaging
      techniques. Arterial and venous vessels are unambiguously differentiated using a
      dynamic contrast-enhanced NIR-II imaging technique on the basis of their distinct
      hemodynamics. Further, the deep tissue penetration and high spatial and temporal
      resolution of NIR-II imaging allow for precise quantifications of blood velocity
      in both normal and ischemic femoral arteries, which are beyond the capabilities
      of ultrasonography at lower blood velocities.

PMID- 23160237
TI  - Abnormal development of NG2+PDGFR-alpha+ neural progenitor cells leads to
      neonatal hydrocephalus in a ciliopathy mouse model.
AB  - Hydrocephalus is a common neurological disorder that leads to expansion of the
      cerebral ventricles and is associated with a high rate of morbidity and
      mortality. Most neonatal cases are of unknown etiology and are likely to have
      complex inheritance involving multiple genes and environmental factors.
      Identifying molecular mechanisms for neonatal hydrocephalus and developing
      noninvasive treatment modalities are high priorities. Here we use a hydrocephalic
      mouse model of the human ciliopathy Bardet-Biedl Syndrome (BBS) and identify a
      role for neural progenitors in the pathogenesis of neonatal hydrocephalus. We
      found that hydrocephalus in this mouse model is caused by aberrant platelet
      derived growth factor receptor alpha (PDGFR-alpha) signaling, resulting in
      increased apoptosis and impaired proliferation of chondroitin sulfate
      proteoglycan 4 (also known as neuron-glial antigen 2 or NG2)(+)PDGFR-alpha(+)
      neural progenitors. Targeting this pathway with lithium treatment rescued
      NG2(+)PDGFR-alpha(+) progenitor cell proliferation in BBS mutant mice, reducing
      their ventricular volume. Our findings demonstrate that neural progenitors are
      crucial in the pathogenesis of neonatal hydrocephalus, and we identify new
      therapeutic targets for this common neurological disorder.

PMID- 23160238
TI  - TRPM4 cation channel mediates axonal and neuronal degeneration in experimental
      autoimmune encephalomyelitis and multiple sclerosis.
AB  - In multiple sclerosis, an inflammatory disease of the central nervous system
      (CNS), axonal and neuronal loss are major causes for irreversible neurological
      disability. However, which molecules contribute to axonal and neuronal injury
      under inflammatory conditions remains largely unknown. Here we show that the
      transient receptor potential melastatin 4 (TRPM4) cation channel is crucial in
      this process. TRPM4 is expressed in mouse and human neuronal somata, but it is
      also expressed in axons in inflammatory CNS lesions in experimental autoimmune
      encephalomyelitis (EAE) in mice and in human multiple sclerosis tissue.
      Deficiency or pharmacological inhibition of TRPM4 using the antidiabetic drug
      glibenclamide resulted in reduced axonal and neuronal degeneration and attenuated
      clinical disease scores in EAE, but this occurred without altering EAE-relevant
      immune function. Furthermore, Trpm4(-/-) mouse neurons were protected against
      inflammatory effector mechanisms such as excitotoxic stress and energy deficiency
      in vitro. Electrophysiological recordings revealed TRPM4-dependent neuronal ion
      influx and oncotic cell swelling upon excitotoxic stimulation. Therefore,
      interference with TRPM4 could translate into a new neuroprotective treatment
      strategy.

PMID- 23160240
TI  - Ways of experiencing participation and factors affecting the activity level after
      nonreconstructed anterior cruciate ligament injury: a qualitative study.
AB  - STUDY DESIGN: Phenomenographic, cross-sectional. OBJECTIVES: To describe ways of
      experiencing participation in activities of individuals with a nonreconstructed
      anterior cruciate ligament injury and to describe the emotional aspects related
      to participation. Further, the objective was to explore factors affecting the
      activity level. BACKGROUND: The importance of assessing different factors (knee
      status, muscle performance, psychological factors, performance-based tests, and
      subjective rating of knee function) after an anterior cruciate ligament injury
      has been emphasized. However, the results of these assessments do not answer the
      question of how the individuals themselves experience their participation in
      activities. METHODS: Semi-structured interviews were conducted with 19
      strategically selected informants (age range, 18-43 years) who had sustained an
      anterior cruciate ligament injury 18 to 67 months previously. A phenomenographic
      approach, which describes individuals' ways of experiencing a phenomenon, was
      used. RESULTS: Five qualitatively different categories were identified: (A)
      unconditioned participation, (B) participation as conditioned by risk appraisal,
      (C) participation as conditioned by experienced control of the knee, (D)
      participation as conditioned by experienced knee impairment, and (E)
      participation as conditioned by neglecting the knee injury. Within each category,
      5 interrelated aspects were discerned: focus, level of performance, activities,
      strategies, and feelings. Categories A, C, and E reflected experiences of full
      participation, whereas categories B and D reflected experiences of modified
      participation. There were mostly positive feelings regarding participation.
      Negative feelings were expressed in category D. Factors affecting the activity
      level were grouped according to the framework of the International Classification
      of Functioning, Disability and Health and described as facilitating or hindering
      the activity level. Facilitating factors included regaining and maintaining
      physical function, regaining confidence in knee function, and learning/relearning
      movement patterns. Hindering factors included fear of injury/reinjury,
      uncontrollable giving way, and loss of motivation. CONCLUSION: With different
      strategies, most of the informants achieved a satisfactory activity level,
      despite impairments and decreased activity level. Both physical and psychological
      factors were described to affect the activity level, as well as time since
      injury.

PMID- 23160239
TI  - Dipeptidylpeptidase 4 negatively regulates colony-stimulating factor activity and
      stress hematopoiesis.
AB  - Enhancement of hematopoietic recovery after radiation, chemotherapy, or
      hematopoietic stem cell (HSC) transplantation is clinically relevant.
      Dipeptidylpeptidase (DPP4) cleaves a wide variety of substrates, including the
      chemokine stromal cell-derived factor-1 (SDF-1). In the course of experiments
      showing that inhibition of DPP4 enhances SDF-1-mediated progenitor cell survival,
      ex vivo cytokine expansion and replating frequency, we unexpectedly found that
      DPP4 has a more general role in regulating colony-stimulating factor (CSF)
      activity. DPP4 cleaved within the N-termini of the CSFs granulocyte-macrophage
      (GM)-CSF, G-CSF, interleukin-3 (IL-3) and erythropoietin and decreased their
      activity. Dpp4 knockout or DPP4 inhibition enhanced CSF activities both in vitro
      and in vivo. The reduced activity of DPP4-truncated versus full-length human GM
      CSF was mechanistically linked to effects on receptor-binding affinity, induction
      of GM-CSF receptor oligomerization and signaling capacity. Hematopoiesis in mice
      after radiation or chemotherapy was enhanced in Dpp4(-/-) mice or mice receiving
      an orally active DPP4 inhibitor. DPP4 inhibition enhanced engraftment in mice
      without compromising HSC function, suggesting the potential clinical utility of
      this approach.

PMID- 23160241
TI  - Sodium citrate vacuum tubes validation: preventing preanalytical variability in
      routine coagulation testing.
AB  - Sometimes in-vitro diagnostic devices (e.g. blood collection tubes) are not
      validated before use or when the producer's brand is changed. The aim of this
      study was to validate five brands of sodium citrate vacuum tubes. Blood specimens
      from 50 volunteers were collected in five different tube brands (I: Venosafe, II:
      VACUETTE, III: BD Vacutainer, IV: LABOR IMPORT and V: S-Monovette). Routine
      coagulation tests [activated partial thromboplastin time (aPTT), prothrombin time
      (PT), and fibrinogen (FIB)] were performed on ACL TOP instrument using HemosIL
      reagents. The significance of the differences between samples was assessed by
      paired Student's t-test, set at P < 0.005. Significant differences were observed
      for: PT when comparing I vs. II, I vs. III, I vs. V, II vs. III, II vs. IV, II
      vs. V, III vs. IV, III vs. V and IV vs. V; aPTT when comparing I vs. II, I vs.
      III, I vs. IV, II vs. IV, III vs. IV and IV vs. V. No differences were observed
      among brands for FIB determination. We suggest that every laboratory management
      should both standardize the procedures and frequently evaluate the quality of in
      vitro diagnostic devices.

PMID- 23160242
TI  - Influence of chronic administration of anabolic androgenic steroids and taurine
      on haemostasis profile in rats: a thrombelastographic study.
AB  - Anabolic androgenic steroids (AAS) are synthetic derivatives of testosterone with
      thrombogenic potential in high doses and long-term administration. Taurine, a
      widely distributed amino-sulfonic acid, is known for its beneficial effects in
      hypercoagulable states. In order to assess the impact of chronic administration
      of high doses of AAS and taurine upon haemostasis process in rats, 40 male Wistar
      rats were divided into four equal groups: control group (group C) - no treatment;
      androgen group (group A) - received 10 mg/kg per week of nandrolone decanoate
      (DECA); taurine (group T) - received oral supplementation of 2% taurine in
      drinking water; androgen and taurine group (group AT) - concomitant
      administration of DECA and taurine. After 12 weeks, blood samples were collected
      and haemostasis parameters were assessed with the thrombelastographic (TEG)
      analysis system: reaction time, clot kinetics (K, alpha), final clot strength,
      coagulation index and the clot lysis (Ly30). Nandrolone significantly decreased
      reaction time in group A compared with control (P<0.001), whereas taurine
      significantly increase reaction time (P=0.01), and this effect was maintained in
      group AT compared with group A (P=0.009). Similar differences between groups have
      been recorded for the clot kinetics parameters K, alpha. The final clot strength
      and coagulation index were significantly increased in group A versus group C
      (P=0.04, respectively P<0.001), but not in group AT versus group C (P>0.05).
      There were no differences in clot lysis, as shown by Ly30. Nandrolone produces an
      accelerated clot development and an increased clot firmness in Wistar rats.
      Taurine association ensures a protective effect against this hypercoagulable
      state, partially restoring the altered parameters of the coagulation profile.

PMID- 23160243
TI  - Psychotherapy in a changing world.

PMID- 23160244
TI  - Diagnosing bipolar disorder in the community setting.
AB  - BACKGROUND: Bipolar disorder (BD) is a common psychiatric illness. Diagnosing
      this condition is challenging, due to the frequent need to make the diagnosis
      based on historical symptoms, the lack of specificity of many of the symptoms,
      and the absence of accurate objective measures to confirm the diagnosis. A lack
      of consensus among psychiatrists as to the breadth of the diagnosis, increasing
      pressures to make a diagnosis quickly in clinical settings, and the availability
      of broader spectrum treatments have also served to foster uncertainty in
      diagnosis. This article examines the process of diagnosing BD, reviews factors
      that can confound the diagnostic process, and discusses how the sensitivity and
      specificity of the diagnosis can be improved. METHODS: A MEDLINE search and a
      manual search of textbooks and abstracts from scientific meetings were conducted.
      Results were limited to publications in English, but no timeframe limitations
      were used. RESULTS: The standard for diagnosing BD remains the psychiatric
      interview, with laboratory, genetic, radiographic, and neuroimaging tests still
      investigational, and psychological tests and questionnaires serving an ancillary
      role. The sensitivity and specificity of the BD diagnosis is less than optimal,
      with the condition being both overlooked and diagnosed when it is not present.
      CONCLUSIONS: Factors leading to diagnostic uncertainty and approaches to improve
      the sensitivity and specificity of the BD diagnosis are discussed. A paradigm for
      differentiating between BD and borderline personality disorder is offered.

PMID- 23160245
TI  - Posttraumatic stress disorder in women with binge eating disorder in primary
      care.
AB  - OBJECTIVE: To examine the frequency and significance of comorbid posttraumatic
      stress disorder (PTSD) in ethnically diverse obese patients with binge eating
      disorder (BED) seeking treatment for obesity and binge eating in primary care.
      METHODS: Participants were a consecutive series of 105 obese women with BED; 43%
      were African- American, 36% were Caucasian, and 21% were Hispanic-American/other.
      Participants were evaluated with reliable semi-structured interviews and
      established measures. RESULTS: Of the 105 women, 25 (24%) met criteria for PTSD.
      PTSD was associated with significantly elevated rates of mood, anxiety, and drug
      use disorders, significantly elevated eating disorder psychopathology (Eating
      Disorder Examination global score and scales), greater depressive affect, and
      lower self-esteem, even though the patients with comorbid PTSD did not have
      higher body mass indexes (BMIs) or greater frequency of binge eating. The
      heightened eating disorder psychopathology and depression and the lower self
      esteem among patients with comorbid PTSD persisted even after controlling for
      anxiety disorder comorbidity. CONCLUSIONS: Our findings suggest that among
      ethnically/ racially diverse obese women with BED who present for obesity and
      binge eating treatment in primary care settings, PTSD is common and is associated
      with heightened psychiatric comorbidity, greater eating disorder psychopathology,
      and poorer psychological functioning.

PMID- 23160246
TI  - "What's in a name?" Delirium by any other name would be as deadly. A review of
      the nature of delirium consultations.
AB  - INTRODUCTION: Delirium is often underdiagnosed, resulting in adverse clinical
      outcomes. The goal of this study was to identify how patients correctly diagnosed
      with delirium differ from those who are misdiagnosed. METHODS: A retrospective
      chart review was conducted using a database of 1,000 consecutive psychiatric
      consultation requests. Patients were identified based on a diagnosis of delirium
      made by the consultation team. Charts were then reviewed for data on race,
      gender, age, time and month of the consultation, documented diagnosis of mental
      illness, and information that would help establish a delirium diagnosis based on
      DSM-IV-TR criteria. Univariate and multivariate analyses were performed. RESULTS:
      Cases were judged to be diagnostically concordant (consultation requested for
      delirium or encephalopathy, n = 30) or discordant (n = 81). The two groups did
      not differ significantly in age, sex, race, time and month of the consultation,
      or documentation of mental illness. The concordant group had a significantly
      greater number of identifiable diagnostic criteria compared to the discordant
      group (mean 3.0 +/- 0.8 criteria vs. 1.9 +/- 1.3 criteria, P < 0.001).
      Identification of individual diagnostic criteria was greater in the concordant
      group, with significant differences for two of four categories, namely acute
      onset (100.0% vs. 50.6%, P < 0.001) and fluctuating course (93.3% vs. 66.7%, P =
      0.004). Multivariate analysis suggested increased odds of identifying delirium if
      more diagnostic criteria were identifiable (OR: 2.355, P < 0.001, confidence
      interval [CI] 1.502-3.690), and increased likelihood of the delirium diagnosis
      being missed if there was documentation of psychiatric illness (OR: 0.387, P =
      0.049, CI: 0.151-0.995). CONCLUSION: This study highlights the need for
      educational programs and easy to implement screening tools to ensure delirium is
      not overlooked.

PMID- 23160247
TI  - Predictive validity of the MMPI-2 clinical, PSY-5, and RC scales for therapy
      disruptive behavior.
AB  - BACKGROUND: Impulsive acts, parasuicidal behavior, and other therapy disruptive
      incidents occur frequently in the treatment of patients with personality
      disorders and increase the risk that patients will drop out of treatment.
      OBJECTIVE: This study examined the predictive validity of the Minnesota
      Multiphasic Personality Inventory (MMPI)-2 Restructured Clinical (RC) and
      Psychopathology Five (PSY-5) Scales for therapy disruptive behavior and compared
      them with the original clinical scales. METHODS: Using an inventory, the
      treatment staff recorded the therapy disruptive behavior of 104 patients with
      personality disorders who were receiving inpatient psychotherapy. RESULTS: Both
      the RC and the PSY-5 scales predicted several categories of therapy disruptive
      behavior, and both scales predicted more categories of therapy disruptive
      behavior than the original clinical scales. Anger outbursts were predicted
      especially well by a combination of two of the RC scales. CONCLUSIONS: The
      information about the MMPI-2 obtained in this study may be helpful in case
      formulation when initiating inpatient treatment for patients with personality
      disorders.

PMID- 23160248
TI  - Clinically important differences in the pharmacokinetics of the ten newer
      "atypical" antipsychotics: Part 3. Effects of renal and hepatic impairment.
AB  - The "atypical" antipsychotics are grouped together based on what they are not
      (i.e., not dopamine-2 selective antagonists like haloperidol). While sharing this
      characteristic, these agents differ substantially in pharmacokinetics and
      pharmacodynamics. The first two columns in this series reviewed the
      bioavailability, half-life, and metabolism of the 10 newer "atypical"
      antipsychotics, including the most recently marketed members of this class
      (asenapine, iloperidone, and lurasidone). This third column in the series
      discusses the effect hepatic and renal impairment has on the clearance and hence
      dosing recommendations for these agents. An understanding of the pharmacokinetic
      differences among the "atypical" antipsychotics discussed in this series of
      columns can help clinicians optimize drug selection and dose for specific
      patients under specific treatment conditions. A subsequent column in the series
      will review the substantial and clinically important pharmacodynamic differences
      among these agents.

PMID- 23160249
TI  - Psychotherapy and psychoanalysts in psychiatric residency training.
AB  - There is a renewed interest in teaching psychotherapy in psychiatry training
      programs in the context of the current accreditation standards for developing
      competency in psychotherapy. However, meeting the standards requires adequate
      faculty, expertise, motivation, and patient population to support a substantive
      didactic and experiential base for residents to develop phase-appropriate
      competence. Psychoanalysts are in a position to provide capable instruction and
      supervision in psychodynamic as well as supportive psychotherapy, but they are
      not evenly distributed in the United States. The psychoanalyst authors
      investigated the experience of psychiatry residency training programs in eastern
      Massachusetts and northeast Ohio with regard to their current practice in
      psychotherapy training in general and psychodynamic psychotherapy in particular.
      They asked about the time given to formal teaching, therapy experience and
      supervision, the composition of the faculty, and the presence of psychoanalysts
      as teachers or supervisors. Personal interviews to clarify aims, attitudes, and
      needs supplemented responses to the questionnaire. This article describes these
      findings and the opportunities and challenges that are evident in the current
      environment of psychiatric training. We found that most programs made substantial
      efforts to teach psychodynamic and cognitive-behavioral therapies, but that
      supportive therapy received less focused attention. The involvement of
      psychoanalysts in teaching was generally welcomed in this sample, but was
      dependent on their availability in the community.

PMID- 23160251
TI  - NAMI in our own voice and NAMI smarts for advocacy: self-narrative as advocacy
      tool.
AB  - In his first Advocacy column for the Journal of Psychiatric Practice, the author
      discusses the importance and relevance of advocacy for all mental health
      professionals and researchers in whatever setting they work. Advocacy efforts can
      and have influenced a range of issues that are important to hospital-based and
      community psychiatrists, private practitioners, and researchers. The author then
      discusses the importance of personal self-narrative as a tool for decreasing
      stigma and increasing understanding of serious mental illness, with a focus on
      two programs developed by the National Alliance on Mental Illness: NAMI In Our
      Own Voice and NAMI Smarts for Advocacy.

PMID- 23160250
TI  - How lawyers view psychiatric experts.
AB  - Good lawyers look for integrity in their expert consultants and expert witnesses.
      They need truthful, accurate information to help them assess and frame cases, win
      or settle them favorably, and/or withdraw when the case has little merit. Experts
      should be well qualified to review, interpret, and eventually testify credibly
      about their portions of the case. They should be able to work with lawyers in the
      lawyers' own arenas (e.g., courts, hearings) and to convey their opinions to
      others, such as juries, clearly and without unnecessary distractions.

PMID- 23160252
TI  - Avatar therapy:  where technology, symbols, culture, and connection collide.
AB  - The topic of "e-therapy" is of great research and clinical interest in 2012. This
      article presents a case study that examines several elements of psychotherapy, as
      administered in the "Second Life" virtual environment. In this case,
      psychotherapy took place primarily via text messaging between two avatars (client
      and therapist) who "sat" in a virtual office. The therapist resided in the United
      States and provided therapy to an individual from a developing nation who was
      currently residing in another more developed Middle Eastern country for work and
      to escape political atrocities being committed in his home country. This case
      example raises many issues that could be explored, including the ethics of
      providing such therapy, cultural competence, technological details, and providing
      therapy across national lines. However, due to the complicated and multifaceted
      nature of providing therapy in a virtual environment, this case presentation
      focuses on technical issues, such as the basics of providing therapy in Second
      Life. Given that the patient in this case used multiple avatars (cartoon-like
      representations of himself) in therapy, the topic of the avatar as the expression
      of internal representations and conflicts is also examined. This case report also
      discusses the patient's presenting problems and elements of the therapeutic
      alliance such as transference and countertransference. Finally, suggestions for
      future research are made. The author posits that mental health professionals can
      now reach at-risk patients (e.g., refugees residing in other countries) whom they
      were not previously able to treat and suggests that mental health practitioners
      may have an ethical duty to research and provide these kinds of services so that
      certain underserved populations may be treated. (Journal of Psychiatric Practice
      2012;18:451-459).

PMID- 23160253
TI  - Undergraduate students' perceptions of practicing psychiatrists.
AB  - This article reports research findings from a survey of 261 students regarding
      their perceptions of psychiatrists. Overall, students view psychiatrists as
      competent and prestigious. At the same time, however, only approximately half of
      respondents reported having a "positive view" of these professionals and around
      one-third were neutral. College students view psychiatrists as effective for
      treating relatively severe mental health problems, although depression was not
      considered to be a psychiatrist's relative strong suit (only half viewed them as
      being effective). Some confusion between psychiatrists and psychologists seemed
      apparent. Although students did not consider the media a highly reliable source
      of information, media sources nonetheless appeared to play a dominant role in
      determining how college students framed psychiatry roles. We discuss the results
      in the context of the need for further education by the specialty of psychiatry
      and the importance of reversing what appears to be some negative stereotyping.

PMID- 23160254
TI  - Good news.

PMID- 23160256
TI  - The origin of photovoltaic responses in BiFeO3 multiferroic ceramics.
AB  - Multiferroic BiFeO(3) (BFO) ceramics with electrodes of indium tin oxide (ITO)
      and Au thin films exhibit significant photovoltaic effects under near-ultraviolet
      illumination (lambda = 405 nm) and show strong dependences on light wavelength,
      illumination intensity, and sample thickness. The correlation between
      photovoltaic responses and illumination intensity can be attributed to photo
      excited and thermally generated charge carriers in the interface depletion region
      between BFO ceramic and ITO thin film. A theoretical model is developed to
      describe the open-circuit photovoltage and short-circuit photocurrent density as
      a function of illumination intensity. This model can be applied to the
      photovoltaic effects in p-n junction type BFO thin films and other systems. The
      BFO ceramic exhibits stronger photovoltaic responses than the ferroelectric Pb(1
      x)La(x)(Zr(y)Ti(1-y))(1-x/4)O(3) (PLZT) ceramics under near-ultraviolet
      illumination. Comparisons are made with other systems and models for the
      photovoltaic effect.

PMID- 23160257
TI  - Child pornography and likelihood of contact abuse: a comparison between contact
      child sexual offenders and noncontact offenders.
AB  - This study examined a sample of 120 adult males convicted of offences involving
      indecent images of children (IIOC); 60 had a previous contact child sexual
      offence (dual offenders) and 60 had no evidence of an offence against a child.
      Analyses explored socio-demographic characteristics, previous convictions, and
      access to children. Of the 120 offenders, a subsample of 60 offenders (30 dual
      offenders and 30 non-contact) were further examined in terms of the quantity of
      IIOC, types of IIOC, and offending behavior. The study found the two offender
      groups could be discriminated by previous convictions, access to children, the
      number, proportion, and type of IIOC viewed. The IIOC preferences displayed
      within their possession differentiated dual offenders from non-contact IIOC
      offenders. Within group comparisons of the dual offenders differentiated sadistic
      rapists from sexual penetrative and sexual touching offenders. The paper suggests
      there may be a homology between IIOC possession, victim selection, and offending
      behavior. Implications for law enforcement are discussed in terms of likelihood
      of contact offending and assisting in investigative prioritization. 

PMID- 23160258
TI  - Rebuttal: PTH--a particularly tricky hormone: why measure it at all in kidney
      patients?

PMID- 23160259
TI  - Model comparisons of competing risk and recurrent events for graft failure in
      renal transplant recipients.
AB  - BACKGROUND AND OBJECTIVES: Risk factor analysis of long-term graft survival in
      kidney transplant recipients is usually based on Cox regression models of time to
      first occurrence of doubling of serum creatinine or graft loss (DSCGL). However,
      death is a competing cause of failure, and censoring patients who die could bias
      estimates. We therefore compared estimates of time to first event versus
      estimates that included death as a competing risk and recurrent events. DESIGN,
      SETTING, PARTICIPANTS, & MEASUREMENTS: A Cox regression analysis of 1997-2002
      data from the Assessment of Lescol in Renal Transplant (ALERT) trial population
      identified an eight-factor risk model, by analyzing time to first occurrence of
      DSCGL. The same factors were re-analyzed, allowing for death as competing. The
      probability of survival free of DSCGL was estimated; and two recurrent models
      (marginal and conditional) were used for time to events. RESULTS: Creatinine,
      systolic BP, and HLA-DR mismatches lost 33%-46% of their strength of association
      with DSCGL when death was included as a competing risk. Small changes were
      observed if recurrent events were analyzed in the marginal model. CONCLUSION: The
      relationship between serum creatinine and DSCGL was attenuated when death was
      considered as a competing risk; inclusion of recurrent events had little effect.
      These findings have important implications for analysis and trial design in
      populations at high mortality risk.

PMID- 23160260
TI  - Physical activity in ESRD: time to get moving.

PMID- 23160262
TI  - Removing financial disincentives to organ donation: an acceptable next step?

PMID- 23160261
TI  - Intravenous cyclophosphamide and plasmapheresis in dialysis-dependent ANCA
      associated vasculitis.
AB  - BACKGROUND AND OBJECTIVES: Induction therapy with oral cyclophosphamide (CYP) has
      been a mainstay of treatment in patients with severe renal failure secondary to
      ANCA-associated vasculitis (AAV). Recent evidence proposes using pulsed
      intravenous CYP in less severe disease to minimize adverse events. It is unclear
      if this can be translated to those with dialysis-dependent renal insufficiency.
      DESIGN, SETTING, PARTICIPANTS, & METHODS: All AAV patients presenting between
      2005 and 2010 requiring dialysis at presentation were retrospectively analyzed.
      Patients were treated with plasma exchange, corticosteroids, and intravenous CYP.
      Rate of dialysis independence at 3 and 12 months and adverse effects were
      assessed and compared with the outcome of the plasmapheresis, prednisolone, and
      oral CYP arm of the randomized MEPEX (methylprednisolone versus plasma exchange)
      trial. RESULTS: Forty-one patients were included. At 3 months, 3 (7.3%) patients
      had died on dialysis, 12 (29.3%) remained dialysis dependent, and 26 (63.4%) were
      dialysis independent (creatinine, 2.5 mg/dl; GFR, 26 ml/min per 1.73 m(2)). Four
      patients subsequently reached ESRD at a median time of 83 days. Thirty-seven
      (90%) patients reached 1 year follow-up, 13 (35%) remained dialysis dependent,
      and 24 (65%) had independent renal function. Eleven patients (27%) had episodes
      of leukopenia (white cell count <4*10(9)/L) during CYP therapy and 17 (41%)
      experienced infectious complications. This compares favorably with the dialysis
      dependent cohort treated with plasmapheresis in the MEPEX study in which 51% were
      alive with independent renal function at 1 year. CONCLUSIONS: Intravenous CYP
      used with corticosteroids and plasmapheresis may be an effective alternative to
      oral CYP in patients with dialysis-dependent AAV.

PMID- 23160263
TI  - Rebuttal: the case for routine parathyroid hormone monitoring.

PMID- 23160264
TI  - Microsurgical epididymal sperm aspiration: indications, techniques and outcomes.
AB  - Microsurgical epididymal sperm aspiration (MESA) refers to retrieval of sperm
      containing fluid from optimal areas of the epididymis that are selected and
      sampled using high-power optical magnification provided by an operating
      microscope. Retrieved sperm are subsequently used for intracytoplasmic sperm
      injection (ICSI) to induce fertilization and pregnancy. MESA is considered by
      many experts to be the gold standard technique for sperm retrieval in men with
      obstructive azoospermia given its high yield of quality sperm, excellent reported
      fertilization and pregnancy rates, and low risk of complications. However, MESA
      must be performed in an operating room, requires microsurgical skills and is only
      useful for reproduction using ICSI. Herein we present an overview of the
      evaluation of candidate patients for MESA, the technical performance of the
      procedure and the outcomes that have been reported.

PMID- 23160265
TI  - Male infertility microsurgical training.
AB  - Microsurgical training is imperative for urologists and clinical andrologists
      specializing in male infertility. Success in male infertility microsurgery is
      heavily dependent on the surgeon's microsurgical skills. Laboratory-based
      practice to enhance microsurgical skills improves the surgeon's confidence, and
      reduces stress and operating time, benefiting both the patient and the surgeon.
      This review provides guidelines for setting up a microsurgical laboratory to
      develop and enhance microsurgical skills using synthetic and animal models. The
      role of emerging techniques, such as robotic-assisted microsurgery, is also
      discussed.

PMID- 23160267
TI  - A quantum-mechanical study of the adsorption of prototype dye molecules on rutile
      TiO2(110): a comparison between catechol and isonicotinic acid.
AB  - In this work we present a theoretical investigation of the attachment of catechol
      and isonicotinic acid to the rutile-TiO(2)(110) surface. These molecules can be
      considered as prototypical dyes for use in Gratzel type dye sensitised solar
      cells (DSCs) and are often employed as anchoring groups in both organic and
      organo-metallic sensitisers of TiO(2). Our study focuses on determining the
      lowest energy adsorption mode and discussing the electronic properties of the
      resultant hybrid interface by means of density functional theory (DFT)
      calculations using the hybrid exchange (B3LYP) functional. We find that both
      molecules adsorb dissociatively at the TiO(2) surface giving a type II
      (staggered) heterojunction. Compared to isonicotinic acid, catechol, due to the
      greater hybridisation of its molecular orbitals with the states of the substrate,
      is seen to enhance performance when employed as an anchoring group in dye
      sensitised solar cells.

PMID- 23160266
TI  - The evolution and refinement of vasoepididymostomy techniques.
AB  - Obstructive azoospermia secondary to epididymal obstruction can be corrected by
      microsurgical reconstruction with vasoepididymostomy (VE). Although alternative
      management such as epididymal or testicular sperm aspiration in conjunction with
      intracytoplasmic sperm injection is feasible, various studies have established
      the superior cost-effectiveness of VE as a treatment of choice. Microsurgical VE
      is considered one of the most technically challenging microsurgeries. Its success
      rate is highly dependent on the skills and experience of the surgeons. Various
      techniques have been described in the literature for VE. We have pioneered a
      technique known as longitudinal intussusception VE (LIVE) in which the epididymal
      tubule is opened longitudinally to obtain a larger opening to allow its tubular
      content to pass through the anastomosis. Our preliminary data demonstrated a
      patency rate of over 90%. This technique has been widely referenced in the recent
      literature including robotic-assisted microsurgery. The history of the
      development of different VE approaches, the preoperative evaluation along with
      the techniques of various VE will be described in this article.

PMID- 23160268
TI  - Self-assembled nanoparticle arrays for multiphase trace analyte detection.
AB  - Nanoplasmonic structures designed for trace analyte detection using surface
      enhanced Raman spectroscopy typically require sophisticated nanofabrication
      techniques. An alternative to fabricating such substrates is to rely on self
      assembly of nanoparticles into close-packed arrays at liquid/liquid or liquid/air
      interfaces. The density of the arrays can be controlled by modifying the
      nanoparticle functionality, pH of the solution and salt concentration.
      Importantly, these arrays are robust, self-healing, reproducible and extremely
      easy to handle. Here, we report on the use of such platforms formed by Au
      nanoparticles for the detection of multi-analytes from the aqueous, organic or
      air phases. The interfacial area of the Au array in our system is ~25 mm(2) and
      can be made smaller, making this platform ideal for small-volume samples, low
      concentrations and trace analytes. Importantly, the ease of assembly and rapid
      detection make this platform ideal for in-the-field sample testing of toxins,
      explosives, narcotics or other hazardous chemicals.

PMID- 23160269
TI  - Bonding-induced thermal conductance enhancement at inorganic heterointerfaces
      using nanomolecular monolayers.
AB  - Manipulating interfacial thermal transport is important for many technologies
      including nanoelectronics, solid-state lighting, energy generation and
      nanocomposites. Here, we demonstrate the use of a strongly bonding organic
      nanomolecular monolayer (NML) at model metal/dielectric interfaces to obtain up
      to a fourfold increase in the interfacial thermal conductance, to values as high
      as 430 MW m(-2) K(-1) in the copper-silica system. We also show that the approach
      of using an NML can be implemented to tune the interfacial thermal conductance in
      other materials systems. Molecular dynamics simulations indicate that the
      remarkable enhancement we observe is due to strong NML-dielectric and NML-metal
      bonds that facilitate efficient heat transfer through the NML. Our results
      underscore the importance of interfacial bond strength as a means to describe and
      control interfacial thermal transport in a variety of materials systems.

PMID- 23160270
TI  - Emergence of superconductivity from the dynamically heterogeneous insulating
      state in La(2-x)Sr(x)CuO4.
AB  - A central issue for copper oxides is the nature of the insulating ground state at
      low carrier densities and the emergence of high-temperature superconductivity
      from that state with doping. Even though this superconductor-insulator transition
      (SIT) is a zero-temperature transition, measurements are not usually carried out
      at low temperatures. Here we use magnetoresistance to probe both the insulating
      state at very low temperatures and the presence of superconducting fluctuations
      in La(2-x)Sr(x)CuO(4) films, for doping levels that range from the insulator to
      the superconductor (x  =  0.03-0.08). We observe that the charge glass behaviour,
      characteristic of the insulating state, is suppressed with doping, but it
      coexists with superconducting fluctuations that emerge already on the insulating
      side of the SIT. The unexpected quenching of the superconducting fluctuations by
      the competing charge order at low temperatures provides a new perspective on the
      mechanism for the SIT.

PMID- 23160271
TI  - Conscious correction of scapular orientation in overhead athletes performing
      selected shoulder rehabilitation exercises: the effect on trapezius muscle
      activation measured by surface electromyography.
AB  - STUDY DESIGN: Controlled laboratory study. OBJECTIVES: To assess the effect of
      conscious correction of scapular orientation on the activation of the 3 sections
      of the trapezius muscle during shoulder exercises in overhead athletes with
      scapular dyskinesis. BACKGROUND: Previous research has led to the recommendation
      of 4 exercises for training of the trapezius muscle: prone extension, sidelying
      external rotation, sidelying forward flexion, and prone horizontal abduction with
      external rotation. However, the extent to which conscious correction of scapular
      orientation impacts trapezius muscle activation levels during these exercises is
      unknown. METHODS: Absolute (upper trapezius [UT], middle trapezius [MT], lower
      trapezius [LT]) and relative (UT/MT and UT/LT) muscle activation levels were
      determined with surface electromyography in 30 asymptomatic overhead athletes
      with scapular dyskinesis, during 4 selected exercises performed with and without
      conscious correction of scapular orientation. Repeated-measures analyses of
      variance were used to determine if a voluntary scapular orientation correction
      strategy influenced the activation levels of the different sections of the
      trapezius during each exercise. RESULTS: With conscious correction of scapular
      orientation, activation levels of the 3 sections of the trapezius muscle
      significantly increased during prone extension (mean +/- SD difference: UT, 5.9%
      +/- 8.6% maximal voluntary isometric contraction [MVIC]; MT, 13.8% +/- 11.0%
      MVIC; LT, 9.8% +/- 10.8% MVIC; P<.05) and sidelying external rotation (UT, 2.2%
      +/- 4.4% MVIC; MT, 6.7% +/- 10.6% MVIC; LT, 13.3% +/- 24.4% MVIC; P<.05). There
      was no difference between conditions for sidelying forward flexion and prone
      horizontal abduction with external rotation. The UT/MT and UT/LT ratios were
      similar between conditions for all 4 exercises. CONCLUSION: Conscious correction
      of scapular orientation during the prone extension and sidelying external
      rotation exercises can be used to increase the activation level in the 3 sections
      of the trapezius in overhead athletes with scapular dyskinesis. Although lack of
      kinematic data limits the interpretation of the results, this study suggests that
      conscious correction of scapular orientation can be performed without altering
      the favorable UT/MT and UT/LT ratios that have been previously reported for these
      exercises.

PMID- 23160272
TI  - Long-term outcomes of 2 cervical laminoplasty methods: midline splitting versus
      unilateral single door.
AB  - BACKGROUND: Two major current methods are midline splitting laminoplasty (MSL)
      and unilateral single-door laminoplasty (USDL). Few studies have compared the 2
      techniques. METHODS: We retrospectively analyzed the outcomes of 100 consecutive
      myelopathy patients who underwent decompressive laminoplasty between January 2004
      and June 2008. The mean follow-up duration was 48.2 months. RESULTS: The mean
      Japanese Orthopedic Association scores changed from 6.9 to 11.9 in the MSL group
      and from 6.2 to 12.4 in the USDL group, resulting in mean calculated recovery
      rates of 55.5% and 63.0%, respectively (P = 0.14). Mean cervical lordosis
      declined from 12.0 to 10.2 degrees in the MSL group and from 10.3 to 8.5 degrees
      in the USDL group (P = 0.24). Mean cervical range of motion declined from 27.8 to
      25.6 degrees in the MSL group, and from 23.4 to 16.0 degrees in the USDL group (P
      = 0.38). Bony spinal canal dimension increased from 201.2 to 280.8 mm in the MSL
      group and from 204.3 to 331.7 mm in the USDL group (P < 0.001). In the USDL
      group, 6 patients experienced postoperative neck pain, 7 experienced C5 palsy,
      and 2 experienced cerebrospinal fluid leakage. No such complications occurred in
      the MSL group (P >= 0.05 for both complications). CONCLUSIONS: MSL and USDL
      patients had similar long-term clinical and radiologic outcomes, except that bony
      canal expansion was greater in the latter. We believe that removal of the
      ligamentum flavum and drilling of the internal bony edge were factors in the
      favorable clinical outcomes and low rate of complications in the MSL group.

PMID- 23160273
TI  - Influence of surgical experience on the efficiency of discectomy in TLIF: a
      cadaveric testing in 40 levels.
AB  - STUDY DESIGN: Cadaveric study. OBJECTIVE: The purpose of this study was to assess
      the influence of surgical experience on the efficiency of lumbar discectomy in
      open transforaminal lumbar interbody fusion. SUMMARY OF BACKGROUND DATA: There is
      limited knowledge about the efficiency of discectomy among surgeons. As a first
      study, we are evaluating the effect of surgical experience on it. METHODS: Manual
      and powered discectomies were randomized and performed by 3 attending spine
      surgeons and 2 clinical spine fellows. Each discectomy procedure was analyzed for
      the area of complete endplate preparation, total elapsed time, and number of
      instrument passes. The surface area of discectomy at each endplate was measured
      utilizing digital imaging and the appropriate software. For the purpose of the
      analysis, the superior and the inferior endplates were divided into ipsilateral
      and contralateral halves, and each half was further divided into ventral and
      dorsal quadrants. Each quadrant was analyzed in a blinded manner by 2 observers.
      RESULTS: A total of 40 discectomies were performed on 9 fresh-frozen cadaveric
      torsos between the levels T12 and S1. A powered discectomy device was used in
      levels 9 and 11 by the attendings. Manual discectomy was performed in 11 levels
      by the spine fellows and 9 by the spine attendings. No significant difference was
      observed between the spine fellows and spine attendings when the manual
      instruments were used (P = 0.924). However, the spine attending surgeon group had
      a significantly increased total area of discectomy compared with the fellows (P =
      0.003). No significant difference was observed between the groups when instrument
      passes or the total elapsed time were compared either utilizing the manual or the
      powered technique. CONCLUSIONS: Our results demonstrate that a satisfactory
      discectomy may be performed by surgeons with relatively less surgical experience
      in the transforaminal approach using a powered discectomy device.

PMID- 23160274
TI  - Practice injury rates in collegiate sports.
AB  - OBJECTIVE: The objective of this article was to explore the differences in
      practice injury rates for select National Collegiate Athletic Association (NCAA)
      sports within and across sport by preseason, in-season, and postseason. This
      article will explore the relationship of practice injury rates by fall, winter,
      and spring sports as well as by Divisions I, II, and III. DESIGN: Descriptive
      epidemiology study. SETTING: NCAA schools. PATIENTS: NCAA athletes. MAIN OUTCOME
      MEASURES: Injury. RESULTS: In all sports across all seasons, preseason practice
      injury rates [6.3 per 1000 athletic exposure (A-E)] were higher than in-season
      (2.3 per 1000 A-E). Fall sports had an overall preseason practice injury rate of
      7.4 (per 1000 A-E) compared with 7.0 (per 1000 A-E) for winter and 3.5 (per 1000
      A-E) for spring sports. Women's soccer had the highest preseason injury rate of
      9.5 (per 1000 A-E). Men's football had the highest increased risk of injury
      comparing preseason with in-season practice injury (3.47 per 1000 A-E).
      CONCLUSIONS: The recognition that preseason practice injury rates are higher
      compared with in-season and postseason practice injury rates can create an
      opportunity for athletes, coaches, and medical personnel to identify prevention
      strategies to reduce preseason injury risk.

PMID- 23160275
TI  - Effect of Ramadan observance on maximal muscular performance of trained men.
AB  - OBJECTIVE: To assess the influence of Ramadan fasting on maximal performance of
      moderately trained young men using various tests of muscle performance. DESIGN:
      Comparison of Ramadan fasting (n = 10) versus control group (n = 10) over 3 test
      sessions, before Ramadan (B), at the end of the first week of Ramadan (R-1), and
      during the fourth week of Ramadan (R-4). SETTING: At each 2-day test session, 4
      tests were performed in the same order: measurement of vertical jump height (VJH)
      and a force-velocity test using the arms on day 1, and measurement of handgrip
      force (HGF), and a force-velocity test using the legs on day 2. PARTICIPANTS:
      Twenty trained men. MAIN OUTCOME MEASURES: Maximal power of the arms and of the
      legs (force-velocity testing), vertical jump performance, HGF, anthropometric
      data, dietary intake, hemoglobin, and hematocrit. RESULTS: Two-way analyses of
      variance (group * time) showed Ramadan fasters with decreased maximal anaerobic
      power of the arms (Wmax-A) and legs (Wmax-L) at R-1, with a partial return of arm
      data to initial values at R-4. Vertical jump height and HGF remained unchanged
      throughout. Other changes in Ramadan observers were a decreased energy intake and
      a decrease of plasma volume at R-1. CONCLUSIONS: These results suggest that
      Ramadan observance initially had detrimental effects on Wmax-A, and Wmax-L, with
      a tendency to recovery by week 4 of Ramadan. Reductions of total energy intake
      and intramuscular glycogen may contribute to the reduced Wmax-A and Wmax-L during
      Ramadan fasting.

PMID- 23160277
TI  - Whole exome sequencing identified a novel zinc-finger gene ZNF141 associated with
      autosomal recessive postaxial polydactyly type A.
AB  - BACKGROUND: Postaxial polydactyly (PAP) type A is characterised by well-formed
      functionally developed 5th digit duplication in hands and/or feet. It is
      genetically heterogeneous condition, inherited both in autosomal recessive and
      dominant manners. To date one autosomal recessive and four autosomal dominant
      loci have been mapped on human chromosomes. In the present study we have
      investigated a consanguineous Pakistani family segregating autosomal recessive
      PAP type A to identify the gene responsible for this phenotype. METHODS: Whole
      exome sequencing combined with homozygosity mapping and array comparative genomic
      hybridisation (aCGH) analysis was used to search for a genetic cause of PAP type
      A in the present study. RESULTS: Exome sequencing identified a missense mutation
      (c.1420C>T; p.Thr474Ile) in all the affected individuals of the family, in the
      gene ZNF141, mapped to the telomeric region on chromosome 4p16.3. CONCLUSION:
      This study revealed involvement of a zinc finger gene ZNF141 in causing autosomal
      recessive PAP type A, which may open up interesting perspectives into the
      function of this protein in limb development.

PMID- 23160276
TI  - Identification of a functional variant in the KIF5A-CYP27B1-METTL1-FAM119B locus
      associated with multiple sclerosis.
AB  - BACKGROUND AND AIM: Several studies have highlighted the association of the
      12q13.3-12q14.1 region with coeliac disease, type 1 diabetes, rheumatoid
      arthritis and multiple sclerosis (MS); however, the causal variants underlying
      diseases are still unclear. The authors sought to identify the functional variant
      of this region associated with MS. METHODS: Tag-single nucleotide polymorphism
      (SNP) analysis of the associated region encoding 15 genes was performed in 2876
      MS patients and 2910 healthy Caucasian controls together with expression
      regulation analyses. RESULTS: rs6581155, which tagged 18 variants within a region
      where 9 genes map, was sufficient to model the association. This SNP was in total
      linkage disequilibrium (LD) with other polymorphisms that associated with the
      expression levels of FAM119B, AVIL, TSFM, TSPAN31 and CYP27B1 genes in different
      expression quantitative trait loci studies. Functional annotations from
      Encyclopedia of DNA Elements (ENCODE) showed that six out of these rs6581155
      tagged-SNPs were located in regions with regulatory potential and only one of
      them, rs10877013, exhibited allele-dependent (ratio A/G=9.5-fold) and orientation
      dependent (forward/reverse=2.7-fold) enhancer activity as determined by
      luciferase reporter assays. This enhancer is located in a region where a long
      range chromatin interaction among the promoters and promoter-enhancer of several
      genes has been described, possibly affecting their expression simultaneously.
      CONCLUSIONS: This study determines a functional variant which alters the enhancer
      activity of a regulatory element in the locus affecting the expression of several
      genes and explains the association of the 12q13.3-12q14.1 region with MS.

PMID- 23160279
TI  - Ferromagnetic Cu-O-Cu coupling in CaCu3Sn4O12 probed by neutron diffraction.
AB  - The A-site ordered perovskite oxide with the formula CaCu(3)Sn(4)O(12) has been
      synthesized in polycrystalline form under moderate pressure conditions (3.5 GPa)
      in combination with high temperature (1000  degrees C). This oxide crystallizes
      in the cubic space group [Formula: see text] (no. 204) with the unit-cell
      parameter a = 7.64535(6) A at 300 K. The SnO(6) network is extremely tilted,
      giving rise to a square planar coordination for Cu(2+) cations. The non-magnetic
      character of Sn(4+) offers an excellent opportunity to probe the magnetism of
      Cu(2+) at the A sublattice in CaCu(3)Sn(4)O(12). Magnetic susceptibility shows
      that this compound is ferromagnetic below T(C) = 10 K, which is an unusual
      magnetic behaviour in cuprates. This peculiar aspect has been examined by neutron
      powder diffraction. The refinement of the magnetic structure at 4 K indeed
      indicates a parallel coupling between Cu(2+) spins with a magnetic moment of 0.5
      MU(B)/Cu atom.

PMID- 23160280
TI  - Streaming fragment assignment for real-time analysis of sequencing experiments.
AB  - We present eXpress, a software package for efficient probabilistic assignment of
      ambiguously mapping sequenced fragments. eXpress uses a streaming algorithm with
      linear run time and constant memory use. It can determine abundances of sequenced
      molecules in real time and can be applied to ChIP-seq, metagenomics and other
      large-scale sequencing data. We demonstrate its use on RNA-seq data and show that
      eXpress achieves greater efficiency than other quantification methods.

PMID- 23160283
TI  - The global perspective on irritable bowel syndrome: a Rome Foundation-World
      Gastroenterology Organisation symposium.
AB  - Although irritable bowel syndrome (IBS) is common worldwide, there is uncertainty
      regarding similarities and differences in geographical regions and cultural
      groups. For example, are Western diagnostic criteria applicable to other groups?
      The interaction between culture and health can impact quality of care and health
      outcomes and, in research, cause methodological shortcomings that lead to bias
      and inappropriate interpretations of research results. Two central questions are:
      do physicians have the cross-cultural competence to effect a participatory model
      of care; and do we have sufficient knowledge and experience in conducting
      multinational, cross-cultural research? The Rome Foundation and the World
      Gastroenterology Organisation convened a symposium to foster interest in the
      global aspects of IBS, foster cross-cultural competence, improve multinational
      IBS research, foster international networks for IBS research, increase awareness
      of culture's impact on patient care and research in the functional
      gastrointestinal disorders (FGIDs), address cross-cultural issues in
      multinational clinical drug trials, and facilitate the development of patient
      reported outcome measures for FGID research across cultures. This review
      summarizes key points and messages.

PMID- 23160281
TI  - Digestion and depletion of abundant proteins improves proteomic coverage.
AB  - Two major challenges in proteomics are the large number of proteins and their
      broad dynamic range in the cell. We exploited the abundance-dependent Michaelis
      Menten kinetics of trypsin digestion to selectively digest and deplete abundant
      proteins with a method we call DigDeAPr. We validated the depletion mechanism
      with known yeast protein abundances, and we observed greater than threefold
      improvement in low-abundance human-protein identification and quantitation
      metrics. This methodology should be broadly applicable to many organisms,
      proteases and proteomic pipelines.

PMID- 23160284
TI  - The effects of gender and age on evaluation of trainees and faculty in
      gastroenterology.
AB  - OBJECTIVES: We studied whether differences exist in evaluation scores of faculty
      and trainees in gastroenterology (GI) based on the gender of the evaluator or
      evaluatee, or the evaluator-evaluatee gender pairing. METHODS: We examined
      evaluations of faculty and trainees (GI fellows and internal medicine residents
      rotating on GI services), using mixed linear models to assess effects of the four
      possible evaluator-evaluatee gender pairings. Potential confounding variables
      were adjusted for, and random effects were used to account for repeated
      assessments. RESULTS: For internal medicine (IM) residents, no difference in
      evaluation scores based on gender was found. Resident age was negatively
      associated with performance rating, while percentage correct on the in-training
      examination (ITE) was positively associated. For GI fellows, the interaction
      between evaluator and evaluatee gender was significant. Fellow age and
      international medical graduate (IMG) status were negatively associated with
      performance rating, while ITE percentage correct was positively associated. For
      faculty, no difference was found in evaluation scores by IM residents based on
      the gender of the evaluated faculty or the evaluating resident, although the
      interaction between the evaluator and the evaluatee gender was significant.
      Gender had a significant marginal effect on faculty scores by GI fellows, with
      female faculty receiving lower scores. The interaction between evaluator and
      evaluatee gender was also significant for evaluations by fellows. Faculty age was
      negatively associated with performance rating. DISCUSSION: Gender, age, and ITE
      performance are associated with evaluation scores of GI trainees and faculty at
      our institution. The interaction of evaluator and evaluatee gender appears to
      play a more critical role in evaluation scoring than the gender of the evaluatee
      or evaluator in isolation.

PMID- 23160285
TI  - Functional dyspepsia and gastroparesis: one disease or two?

PMID- 23160286
TI  - Images of the month: rectal ganglioneuromatosis with polyps.

PMID- 23160292
TI  - Linaclotide: promising IBS-C efficacy in an era of provisional study endpoints.
AB  - Recent disappointing developments in the pharmacotherapy of irritable bowel
      syndrome (IBS) have not dampened the enthusiasm surrounding linaclotide, a novel
      guanylate cyclase-C agonist for the management of constipation-predominant IBS
      (IBS-C). Two recent phase 3 studies reporting on a single, daily dose of
      linaclotide are presented in this issue of the American Journal of
      Gastroenterology. Importantly, these studies are the first to examine a
      provisional Food and Drug Administration (FDA) combined response endpoint for IBS
      C, which mandates improvements of both abdominal pain and defecatory symptoms.
      Potential limitations of this FDA endpoint relate to a lack of inclusion of other
      potentially important IBS symptoms and an inability to directly compare findings
      with other recent IBS-C trials. Both studies successfully reached this endpoint
      in approximately one-third of study subjects, resulting in numbers needed to
      treat (NNT) of five to eight, to achieve an FDA responder. Individual symptom
      responses to linaclotide were seen in nearly 50% of participants, and potential
      explanations for these discrepancies when compared with the FDA endpoint are
      offered. Adequate relief measures also were assessed and, with NNTs of 3.4-6.8,
      compared favorably with other contemporary IBS-C studies. Overall, both
      linaclotide trials found the medication to be safe in terms of serious adverse
      events, though the secretagogue mechanism of action led to diarrhea in
      approximately one in five subjects. Together, these studies inspire several other
      important questions regarding linaclotide, including its role in the management
      of IBS-C relative to existing treatment options, such as lubiprostone. Greater
      clinical use of linaclotide will reveal whether the observed responses measured
      with the FDA provisional endpoint will translate into real-world experiences of
      improvement in IBS patients.

PMID- 23160293
TI  - Differences in intestinal microbial composition in children with IBS-what does it
      all mean?
AB  - Humans harbor complex microbial communities that cover the skin and the mucosal
      surfaces, including the gastrointestinal mucosa. The intestinal microbiota has
      coevolved with humans and has a key role in immune and functional gut maturation,
      maintenance of homeostasis as well as regulation of functions beyond the
      gastrointestinal tract. On the other hand it is becoming apparent that
      compositional, metabolic, or genetic changes in this ecosystem (dysbiosis) are
      associated with disease. The development of high-throughput approaches to analyze
      the intestinal microbiota has increased markedly our knowledge of the intestinal
      microbiome. Although distinct associations between gut microbial communities and
      inflammatory bowel disease (IBD), irritable bowel syndrome (IBS), and celiac
      disease (CD) have been identified in adult individuals, no direct causal link to
      disease has been established. The relationship between dysbiosis and
      gastrointestinal diseases remains, thus far, circumstantial. This emphasizes the
      importance of studying the composition, diversity, and metabolic capacity of the
      intestinal microbiota in the context of mechanisms of disease and clinical
      phenotypes.

PMID- 23160295
TI  - Should we standardize the 1,700-year-old fecal microbiota transplantation?

PMID- 23160296
TI  - Obstetric trauma, pelvic floor injury and fecal incontinence: a population-based
      case-control study.

PMID- 23160298
TI  - Corrections regarding endotherapy for Barrett's esophagus.

PMID- 23160300
TI  - Endotherapy for Barrett's Esophagus.

PMID- 23160301
TI  - Divisum may be preserving pancreatic function in CFTR patients-but at a cost.

PMID- 23160302
TI  - A rare presentation of abdominal pain: idiopathic mesenteric phlebosclerosis.

PMID- 23160303
TI  - The entire predictive value of the prometheus IBD sgi diagnostic product may be
      due to the three least expensive and most available components.

PMID- 23160304
TI  - Transmural eosinophilic infiltration and fibrosis in a patient with non-traumatic
      Boerhaave's syndrome due to eosinophilic esophagitis.

PMID- 23160305
TI  - Steinstrasse formation after extracorporeal shock wave lithotripsy for pancreatic
      stones.

PMID- 23160306
TI  - The importance of full-thickness jejunal biopsy in diagnosing inflammatory
      neuromuscular gastrointestinal disorders.

PMID- 23160308
TI  - The role of lung epithelial ligands for Siglec-8 and Siglec-F in eosinophilic
      inflammation.
AB  - PURPOSE OF REVIEW: Siglec-8 and Siglec-F are single pass transmembrane inhibitory
      receptors found on the surface of human and mouse eosinophils, respectively, but
      very little is known about their physiologic glycan ligands. This article reviews
      the latest knowledge on this topic and outlines the strategies being used to
      further define the production and glycobiochemical nature of these molecules in
      the lung. RECENT FINDINGS: Both Siglec-8 and Siglec-F recognize the same glycan
      structure, namely 6'-sulfated sialyl Lewis X, as determined using glycan array
      technologies. Studies have identified alpha2,3-linked sialylated glycoprotein
      structures localized to mouse airway epithelium in tissue sections, where their
      constitutive expression requires the specific sialyltransferase St3gal3.
      Expression of these ligands in lung is enhanced during allergic inflammation and
      by cytokines such as IL-13, and is maintained in primary air-liquid interface
      cultures of mouse lung epithelium. Further characterization suggests that they
      are high molecular weight sialylated proteins, putatively mucins. By combining
      analytic glycomics, glycoproteomic mapping, and further in-vitro eosinophil
      experimentation including the ability of candidate structures to enhance
      eosinophil apoptosis, a finely detailed appreciation of the structural
      requirements for productive Siglec-8 and Siglec-F engagement should soon emerge.
      SUMMARY: An enhanced understanding of Siglec-F, Siglec-8, and their ligands
      should improve our understanding of endogenous lung pathways limiting the
      survival of eosinophils within the airway in diseases such as asthma. Knowledge
      of this biology may also result in novel opportunities for drug development
      involving glycans and glycomimetics that selectively bind to Siglec-8 and induce
      eosinophil death.

PMID- 23160310
TI  - Synthesis and potential use of 1,8-naphthalimide type (1)O2 sensor molecules.
AB  - New double (fluorescent and spin) sensor molecules containing 4-amino substituted
      1,8-naphthalimide as a fluorophore and a sterically hindered amine (pre
      nitroxide) or pyrroline nitroxide as a quencher and radical capturing moiety were
      synthesized. All sensors were substituted with a diethylaminoethyl side-chain to
      increase the water solubility. Steady state fluorescence properties of these
      compounds and their responses to ROS in vitro are reported with perspectives of
      plant physiology use in vivo.

PMID- 23160311
TI  - Magnetic symmetries in neutron and resonant x-ray Bragg diffraction patterns of
      four iridium oxides.
AB  - The magnetic properties of Sr(2)IrO(4), Na(2)IrO(3), Sr(3)Ir(2)O(7) and CaIrO(3)
      are discussed, principally in the light of experimental data in recent literature
      for Bragg intensities measured in x-ray diffraction with enhancement at iridium L
      absorption edges. The electronic structure factors we report, which incorporate
      parity-even and acentric entities, serve the immediate purpose of making full use
      of crystal and magnetic symmetry to refine our knowledge of the magnetic
      properties of the four iridates from resonant x-ray diffraction data. They also
      offer a platform on which to interpret future investigations, using dichroic
      signals, resonant x-ray diffraction and neutron diffraction, for example, as well
      as ab initio calculations of electronic structure. Unit-cell structure factors,
      suitable for x-ray Bragg diffraction enhanced by an electric dipole-electric
      dipole (E1-E1) event, reveal exactly which iridium multipoles are visible, e.g.,
      a magnetic dipole parallel to the crystal c-axis (z-axis) and an electric
      quadrupole with yz-like symmetry in the specific case of CaIrO(3). Magnetic space
      groups are assigned to Sr(2)IrO(4), Sr(3)Ir(2)O(7) and CaIrO(3), namely, P(I)cca,
      P(A)ban and Cm'cm', respectively, in the Belov-Neronova-Smirnova notation. The
      assignment for Sr(2)IrO(4) is possible because of our new high-resolution neutron
      diffraction data, gathered on a powder sample. In addition, the new data are used
      to show that the ordered magnetic moment of an Ir(4+) ion in Sr(2)IrO(4) does not
      exceed 0.29(4) MU(B). Na(2)IrO(3) has two candidate magnetic space-groups that
      are not resolved with currently available resonant x-ray data.

PMID- 23160309
TI  - Single-step test for unilateral limb ability following total knee arthroplasty.
AB  - STUDY DESIGN: Secondary analysis of a cohort enrolled in a prospective,
      randomized, longitudinal clinical trial. OBJECTIVES: The single-step test (SST)
      was evaluated to assess its intertester reliability, validity as a test of
      activity limitation, and responsiveness to change for patients after unilateral
      total knee arthroplasty (TKA). The SST was also examined to determine whether it
      could differentiate between the surgical and nonsurgical lower limbs of patients
      after unilateral TKA and between the surgical limbs of patients after TKA and the
      limbs of healthy controls. BACKGROUND: Tests of functional ability for patients
      recovering from TKA cannot differentiate the contribution of each limb to
      performance outcome. A test of unilateral limb ability would provide a metric for
      assessing the surgical lower extremity, without the confounder of the status of
      the contralateral lower extremity. METHODS: Intertester reliability was assessed
      between clinicians and between a clinician and a switch mat. Patients who
      underwent unilateral TKA were tested at initial outpatient physical therapy
      evaluation, at 3 months after TKA, and at 1 year after TKA. RESULTS: The
      assessment of function with the SST was determined to be reliable between testers
      when using a stopwatch. SST times were significantly correlated with other
      measures of lower extremity functional performance, providing evidence of its
      validity in patients after TKA. The SST was responsive to treatment in patients
      after TKA, with improvements in time for test completion. Performance on the SST
      also differed between limbs of patients after TKA and when comparing the limbs of
      healthy controls to those of patients after TKA. CONCLUSION: The SST is a
      reliable measure between testers and a valid and responsive test of activity
      limitations when assessing unilateral lower extremity impairments in patients
      after TKA.

PMID- 23160312
TI  - TiO2 nanotube (T_NT) surface treatment revisited: Implications of ZnO, TiCl4, and
      H2O2 treatment on the photoelectrochemical properties of T_NT and T_NT-CdSe.
AB  - The surface treatment of an anodized TiO(2) nanotube (T_NT) is very desirable for
      enhancing its photoelectrochemical properties and often is a prerequisite to
      deposition of any overlying layer for photoactivity efficiency improvement. This
      study provides a comparative analysis of the effects of such surface treatments
      and the mechanistic insights behind the observed improvements in the performance
      of the treated T_NTs. T_NT surface treatment using three approaches, viz.,
      TiCl(4), Zn(NH(3))(4)(2+), and H(2)O(2) is examined. TiCl(4) and Zn(NH(3))(4)(2+)
      treatment results in the formation of discontinuous islands of the respective
      oxides with 5-10 nm and 15-20 nm diameter particles. TiCl(4) treatment
      demonstrates an increase of 7.4% in photovoltage and is the most effective of the
      three approaches. Zn(NH(3))(4)(2+) treatment also results in an ~2% increase in
      photovoltage. However, a surface treatment of T_NT using H(2)O(2) results only in
      a favourable shift in flatband potential (80 mV). The T_NTs are rendered
      ineffective as H(2)O(2) treatment causes the destabilization of the T_NT at the
      base. Finally, the activity of an overlying chalcogenide layer is improved with
      the TiCl(4) and Zn(NH(3))(4)(2+) treatment (and not with H(2)O(2)) as evident
      from the photoelectrochemical responses: (J(T_NT-TiO(2)-CdSe) > J(T_NT-ZnO-CdSe)
      > J(T_NT-CdSe) > J(T_NT-H(2)O(2)-CdSe)).

PMID- 23160313
TI  - Eighth triennial toxicology salary survey.
AB  - This survey serves as the eighth in a series of toxicology salary surveys
      conducted at 3-year intervals and beginning in 1988. An electronic survey
      instrument was distributed to 5800 individuals including members of the Society
      of Toxicology, American College of Toxicology, and 23 additional professional
      organizations. Question items inquired about gender, age, degree, years of
      experience, certifications held, areas of specialization, society membership,
      employment and income. Overall, 2057 responses were received (response rate
      35.5%). The results of the 2012 survey provide insight into the job market and
      career path for current and future toxicologists.

PMID- 23160316
TI  - A regenerable oxide-based H2S adsorbent with nanofibrous morphology.
AB  - Hydrogen sulphide is found in raw fuels such as natural gas and coal/biomass
      derived syngas. It is poisonous to catalysts and corrosive to metals and
      therefore needs to be removed. This is often achieved using metal oxides as
      reactive adsorbents, but metal oxides perform poorly when subjected to repeated
      cycles of sulphidation and re-oxidation as a result of complex structural and
      chemical changes. Here, we show that Zn-Ti-O-based adsorbents with nanofibrous
      morphology can sustain their initial reactivity and sulphur removal capacity over
      multiple regeneration cycles. These nanostructured sorbents offer rapid reaction
      rates that overcome the gas-transport limitations of conventional pellet-based
      sorbents and allow all of the material to be used efficiently. Regeneration can
      be carried out at the same temperature as the sulphidation step because of the
      higher reactivity, which prevents sorbent deterioration and reduces energy use.
      The efficient regeneration of the adsorbent is also aided by structural features
      such as the growth of hierarchical nanostructures and preferential stabilization
      of a wurtzite phase in the sulphidation product.

PMID- 23160314
TI  - Estrogen-like disruptive effects of dietary exposure to bisphenol A or 17alpha
      ethinyl estradiol in CD1 mice.
AB  - Bisphenol A (BPA) is an endocrine disrupting chemical that is ubiquitous in wild
      and built environments. Due to variability in study design, the disruptive
      effects of BPA have proven difficult to experimentally replicate. This study was
      designed to assess the disruptive actions of dietary BPA exposure, while
      carefully controlling for known confounders. Parental CD1 mice were acclimated to
      defined diet containing BPA (0.03, 0.3, 3, 30, or 300 ppm) or 17alpha-ethinyl
      estradiol (EE; 0.0001, 0.001, and 0.01 ppm) and bred to produce progeny (F1) that
      were maintained through adulthood on the same diet as the parents. In F1 females,
      uterine weights were increased in all EE and the 30-ppm BPA-exposure groups,
      demonstrating model sensitivity and estrogen-like actions of BPA. In BPA-exposed
      females, no treatment-related differences were observed in parental reproductive
      function, or in the timing of puberty and metabolic function in female offspring.
      In F1 males, modest changes in body weight, adiposity and glucose tolerance,
      consistent with improved metabolic function, were observed. Associated with
      increased prolactin and increased circulating testosterone levels,
      balanopreputial separation was accelerated by 0.03 and 3.0 ppm BPA and anogenital
      distance at postnatal day 21 was increased in males by 0.03 ppm BPA. Sperm counts
      were also increased with 3.0 ppm BPA exposures. Overall, BPA was found to have
      modest, sex specific endocrine disruptive effects on a variety of end points
      below the established no observed adverse effect level. The dose response
      characteristics for many of the effects were nonmonotonic and not predictable
      from high-dose extrapolations.

PMID- 23160317
TI  - Attitudes of women from five European countries regarding tobacco control
      policies.
AB  - AIMS: Tobacco-related cancers and, in particular, lung cancer still represents a
      substantial public health epidemic across Europe as a result of high rates of
      smoking prevalence. Countries in Europe have proposed and implemented tobacco
      control policies to reduce smoking prevalence, with some countries being more
      progressive than others. The aim of this study was to examine factors that
      influenced women's attitudes across five European countries relative to
      comprehensive smokefree laws in their countries. METHODS: A cross-sectional
      landline telephone survey on attitudes towards tobacco control laws was conducted
      in five European countries: France, Ireland, Italy, the Czech Republic, and
      Sweden. Attitudinal scores were determined for each respondent relative to
      questions about smokefree laws. Logistic regression models were used to obtain
      odds ratios with 95% confidence intervals. RESULTS: A total of 5000 women were
      interviewed (1000 women from each country). The majority of women, regardless of
      smoking history, objected to smoking in public buses, enclosed shopping centers,
      hospitals, and other indoor work places. More women who had quit smoking believed
      that new tobacco control laws would prompt cessation - as compared with women who
      still smoked. CONCLUSIONS: In general, there is very high support for national
      smokefree laws that cover bars, restaurants, and public transport systems. As
      such laws are implemented, attitudes do change, as demonstrated by the
      differences between countries such as Ireland and the Czech Republic.
      Implementing comprehensive smokefree laws will gain high approval and will be
      associated with prompting people to quit.

PMID- 23160318
TI  - The cost effectiveness of telephone counselling to aid smoking cessation in
      Denmark: a modelling study.
AB  - AIM: To assess the cost-effectiveness of the Danish smoking cessation telephone
      service "quitline". METHODS: The study was based on the number of quitline
      callers in 2005. The outcome was measured as costs per life year saved (LYS)
      based on the assessment in 2001 of continued abstinence over a 12-month period
      (19.0%) and point prevalence of abstinence at 12 months of follow up (29.7%),
      respectively. The costs per LYS are estimated as the annual running costs of
      reactive telephone counselling service divided by the total number of LYS, which
      has been estimated as the difference between current smokers' and ex-smokers'
      life expectancies according to age group and gender based on Danish smoking
      proportions, relative risks of smoking-related mortality of all causes, and
      standard life tables. RESULTS: A total of 511 ex-smokers have been estimated to
      gain 2172 life years based on continued abstinence over 12 months. Using the
      point prevalence abstinence at 12 months, 799 ex-smokers are estimated to gain
      3394 life years. Discounting LYS at 3% p.a., the costs per LYS are ?213 for ex
      smokers with continued abstinence and ?137 for ex-smokers with point prevalence
      abstinence. The sensitivity analysis for a worst-case scenario indicates that the
      costs per LYS are ?1199. For comparison the average costs per LYS of smoking
      cessation interventions in other Danish settings are ?1592 (95% CI ?1547-1636).
      CONCLUSIONS: The Danish reactive telephone counselling to aid smoking cessation
      appears to be cost-effective in comparison with other Danish smoking cessation
      interventions.

PMID- 23160319
TI  - The articles in this supplement should be viewed more as meeting reports than as
      exhaustive and comprehensive review articles. Introduction.

PMID- 23160320
TI  - A tabulated summary of targeted and biologic therapies for non-small-cell lung
      cancer.

PMID- 23160321
TI  - Update on HER1-3 in advanced non-small-cell lung cancer.

PMID- 23160322
TI  - Inhibition of MET receptor tyrosine kinase and its ligand hepatocyte growth
      factor.

PMID- 23160323
TI  - Targeting ALK, ROS1, and BRAF kinases.

PMID- 23160324
TI  - Targeting MEK for the treatment of non-small-cell lung cancer.

PMID- 23160325
TI  - Phosphatidykinosital 3-kinase and mammalian target of rapamycin pathway in non
      small-cell lung cancer.

PMID- 23160326
TI  - Phosphatidylinositol-3-kinase pathway.

PMID- 23160327
TI  - Targeting fibroblast growth factor receptor and discoidin domain receptor 2 in
      non-small-cell lung cancer.

PMID- 23160328
TI  - Miscellaneous agents--cytotoxics and hormonal agents.
AB  - Among the 19 presentations of miscellaneous new agents at this year's meeting,
      several described novel cytotoxics and hormonal agents. The cytotoxic agents
      included microtubule inhibitors (eribulin, nanoparticle albumin-bound paclitaxel,
      peptide-bound paclitaxel), a topoisomerase inhibitor (nanoirinotecan), and an
      alkylating agent (palifosfamide). Hormonal agents included an aromatase inhibitor
      (anastrazole), an estrogen receptor antagonist (fulvestrant), and a selective
      androgen receptor modulator (GTx-024).

PMID- 23160329
TI  - Miscellaneous agents.

PMID- 23160330
TI  - PARP inhibitors in lung cancer.

PMID- 23160331
TI  - Immune therapies for lung cancer.

PMID- 23160332
TI  - Angiogenesis inhibitors.

PMID- 23160333
TI  - Mesothelioma.

PMID- 23160334
TI  - Personalized therapy.

PMID- 23160335
TI  - Histone deacetylase inhibitors in non-small-cell lung cancer.

PMID- 23160336
TI  - Hsp90 inhibitors.

PMID- 23160337
TI  - Doubling down with inhibitors of Notch and Hedgehog signaling pathways.

PMID- 23160338
TI  - Statin therapy and atrial fibrillation:  systematic review and updated meta
      analysis of published randomized controlled trials.
AB  - PURPOSE OF REVIEW: Whether statins may prevent atrial fibrillation remains a
      subject of debate. An updated systematic review of randomized controlled trials
      with statins that collected data on the incidence or recurrence of atrial
      fibrillation was performed. RECENT FINDINGS: Thirty-two published studies with 71
      005 patients were included in the analysis. Overall, the use of statins was
      significantly associated with a decreased risk of atrial fibrillation compared
      with controls [odds ratio (OR) 0.69, 95% confidence interval (CI) 0.57-0.83, P <
      0.0001] with heterogeneous results. The benefit of statin therapy appeared highly
      significant for the prevention of postoperative atrial fibrillation (homogeneous
      OR 0.37, 95% CI 0.28-0.51, P < 0.00001). Benefit was not apparent for the
      prevention of new-onset atrial fibrillation (OR 1.00, 95% CI 0.86-1.15, P = 0.95)
      but was significant for secondary prevention of atrial fibrillation (OR 0.57, 95%
      CI 0.36-0.91, P = 0.02 with significant heterogeneity). There was no reduction in
      the risk of atrial fibrillation with more intensive vs. standard statin regimens
      (OR 1.01, 95% CI 0.77-1.32, P = 0.96). SUMMARY: The use of statins was
      significantly associated with a decreased risk of atrial fibrillation in patients
      with sinus rhythm. The highest benefit was seen for the prevention of
      postoperative atrial fibrillation and in secondary prevention of atrial
      fibrillation, with a heterogeneity that deserves further clarification.

PMID- 23160339
TI  - Electrical storm:  definitions, clinical importance, and treatment.
AB  - PURPOSE OF REVIEW: With increasing use of implantable cardioverter
      defibrillators, physicians are increasingly called upon to manage recurrent
      ventricular tachycardia, sometimes in the form of frequent recurrences known as
      electrical storm (or ventricular tachycardia storm). RECENT FINDINGS: Standard
      antiarrhythmic drug therapy may suppress storms, but, when refractory,
      interventions such as catheter ablation or in some cases surgical cardiac
      denervation may be helpful. Earlier interventional management may confer better
      outcomes than persisting with antiarrhythmic pharmacologic therapy. SUMMARY: The
      clinical syndrome of electrical storm has been defined empirically. An outcome
      derived definition may better guide clinicians on when and how to treat this
      emergent problem. When available, an early interventional approach is preferred.

PMID- 23160340
TI  - CYP3A4 overexpression enhances the cytotoxicity of the antitumor
      triazoloacridinone derivative C-1305 in CHO cells.
AB  - AIM: To examine how the higher expression level of CYP3A4 isoenzyme influenced
      the cytotoxicity of the antitumor triazoloacridinone derivative C-1305 in Chinese
      hamster ovary (CHO) cells. METHODS: Three CHO cell lines were examined: wild-type
      CHO cells; CHO-HR cells with overexpression of human cytochrome P450 reductase
      (CPR); and CHO-HR-3A4 cells with coexpression of human CYP3A4 and CPR. Cellular
      responses caused by C-1305 were monitored using DAPI staining, cell cycle
      analysis, phosphatydilserine externalization analysis and SA-beta-galactosidase
      expression analysis. Cell viability was assessed with simultaneous FDA and PI
      staining. RESULTS: Treatment with C-1305 for 72 h exhibited different levels of
      cytotoxicity in the 3 cell lines, and the values of IC80 in CHO, CHO-HR and CHO
      HR-3A4 cells were 0.087+/-0.005, 0.032+/-0.0001, and 0.064+/-0.0095 MUmol/L,
      respectively. The cell cycle analysis revealed that both CHO and CHO-HR cells
      underwent transient G(2)/M arrest, whereas CHO-HR-3A4 cells did not accumulate in
      this phase. Prolonged exposure up to 120 h caused time-dependent increase in the
      sub-G(1) fraction in all the 3 cell lines. Treatment with C-1305 caused cell
      death through apoptosis and necrosis. However, these processes were more
      pronounced in the transfected CHO cells than in the wild-type cells. The cells
      surviving after C-1305 exposure underwent senescence. CONCLUSION: CYP3A4
      overexpression potently enhances the cellular responses (apoptosis, necrosis and
      senescence) caused by C-1305 in CHO cells.

PMID- 23160341
TI  - 1-Oxoeudesm-11(13)-eno-12,8a-lactone induces G2/M arrest and apoptosis of human
      glioblastoma cells in vitro.
AB  - AIM: To investigate the effects of 1-oxoeudesm-11(13)eno-12,8a-lactone (OEL), a
      novel eudesmane-type sesquiterpene isolated from Aster himalaicus, on the cell
      cycle and apoptosis in human glioblastoma cells in vitro. METHODS: Human
      malignant glioblastoma cell lines U87 and A172 were used. The cytotoxicity of OEL
      was examined using the MTT assay. Cell apoptosis was assessed with DAPI staining
      and flow cytometry. DNA damage was determined by measuring the phosphorylation of
      H2AX using immunofluorescence staining and Western blotting. Cell cycle profiles
      were measured with flow cytometry. The mRNA expression of p53 and p21Waf1/Cip1
      was investigated using real-time PCR. The protein expression of gamma-H2AX,
      caspase-9, caspase-3, p53, p21Waf1/Cip1, cyclin B1, and cdc2 was analyzed with
      Western blotting. RESULTS: Treatment of the malignant glioblastoma cells with OEL
      inhibited the cell growth in dose- and time-dependent manners (the values of
      IC(50) at 48 and 72 h were 29.5 and 16.99 MUmol/L, respectively, in U87 cells;
      7.2 and 9.5 MUmol/L, respectively, in A172 cells). OEL (10-30 MUmol/L) induced
      apoptosis and G(2)/M phase arrest in both U87 and A172 cells. OEL induced the
      phosphorylation of cdc2, a G(2)/M phase cyclin-dependent kinase, and decreased
      the expression of cyclin B1 required for progression through the G(2)/M phase in
      U87 cells. The compound remarkably increased the phosphorylation of H2AX in U87
      cells. Moreover, OEL increased the mRNA and protein levels of p53 and its target
      gene p21(Waf1/Cip1) in U87 cells. The compound also induced p53 phosphorylation.
      Pretreatment with PFT-alpha, a specific inhibitor of p53 transcriptional
      activity, could partially reverse the inhibition of OEL on the viability of U87
      and A172 cells. CONCLUSION: OEL suppresses the growth of human glioblastoma cells
      in vitro via inducing DNA damage, p53-mediated cell cycle arrest and apoptosis,
      thus warrants further studies as a lead compound of anti-glioblastoma drug.

PMID- 23160342
TI  - Droplet sorting based on the number of encapsulated particles using a solenoid
      valve.
AB  - Droplet microfluidics provides a high-throughput platform for screening subjects
      and conditions involved in biology. Droplets with encapsulated beads and cells
      have been increasingly used for studying molecular and cellular biology. Droplet
      sorting is needed to isolate and analyze the subject of interest during such
      screening. The vast majority of current sorting techniques use fluorescence
      intensity emitted by each droplet as the only criterion. However, due to the
      randomness and imperfections in the encapsulation process, typically a mixed
      population of droplets with an uneven number of encapsulated particles results
      and is used for screening. Thus droplet sorting based on the number of
      encapsulated particles becomes necessary for isolating or enriching droplets with
      a specific occupancy. In this work, we developed a fluorescence-activated
      microfluidic droplet sorter that integrated a simple deflection mechanism based
      on the use of a solenoid valve and a sophisticated signal processing system with
      a microcontroller as the core. By passing droplets through a narrow interrogation
      channel, the encapsulated particles were detected individually. The
      microcontroller conducted the computation to determine the number of encapsulated
      particles in each droplet and made the sorting decision accordingly that led to
      actuation of the solenoid valve. We tested both fluorescent beads and stained
      cells and our results showed high efficiency and accuracy for sorting and
      enrichment.

PMID- 23160343
TI  - PS2Br and AsS2X (X = Br, I): similar molecules with completely different shapes-
      a combined experimental and theoretical study.
AB  - By the reaction of solid As(4)S(4) with gaseous Br(2) at a temperature of 410 K
      gaseous AsSBr and AsS(2)Br are formed; the reaction with gaseous I(2) at 468 K
      leads to the formation of AsSI, AsS(2)I, As(2)S(2)I(2) and As(2)S(3)I(2).
      Thermodynamic data on these novel species are obtained by mass spectrometry. The
      experimental findings are extended and confirmed by ab initio quantum chemical
      calculations. Undoubtedly the molecules AsSX (X = Br, I) and As(2)S(2)I(2)
      contain As-atoms in the formal oxidation state III. Unexpectedly, in AsS(2)X
      arsenic is not of formal oxidation state +V but +III: due to the absence of As-S
      pi-bonding, the molecular structure of AsS(2)X is arranged as a dithia-arsirane
      with an AsS(2) three-membered ring. For comparison with AsS(2)X, PS(2)Br is
      investigated for the first time. This high temperature species is planar with
      symmetry C(2v) and phosphorus of the formal oxidation state +V in which the two
      P=S pi-bonds are realized due to their strength over one S-S sigma-bond.
      As(2)S(3)I(2) contains a five-membered As(2)S(3)-ring with one S-S-bond. The
      ionization energies are determined and compared with those obtained from
      calculations; they serve as a further indication for the structures realized in
      these molecules.

PMID- 23160344
TI  - Clinimetric analysis of pressure biofeedback and transversus abdominis function
      in individuals with stabilization classification low back pain.
AB  - STUDY DESIGN: Descriptive laboratory study. OBJECTIVE: To determine if a proposed
      clinical test (pressure biofeedback) could detect changes in transversus
      abdominis (TrA) muscle thickness during an abdominal drawing-in maneuver.
      BACKGROUND: Pressure biofeedback may be used to assess abdominal muscle function
      and TrA activation during an abdominal drawing-in maneuver but has not been
      validated. METHODS: Forty-nine individuals (18 men, 31 women) with low back pain
      who met stabilization classification criteria underwent ultrasound imaging to
      quantify changes in TrA muscle thickness while a pressure transducer was used to
      measure pelvic and spine position during an abdominal drawing-in maneuver. A
      paired t test was used to compare differences in TrA activation ratios between
      groups (able or unable to maintain pressure of 40 +/- 5 mmHg). The groups were
      further dichotomized based on TrA activation ratio (high, greater than 1.5; low,
      less than 1.5). Sensitivity, specificity, and likelihood ratios were calculated.
      RESULTS: There was not a significant difference (P = .57) in TrA activation
      ratios (able to maintain pressure, 1.59 +/- 0.28; unable to maintain pressure,
      1.54 +/- 0.24) between groups. The pressure biofeedback test had low sensitivity
      of 0.22 (95% confidence interval [CI]: 0.10, 0.42) but moderate specificity of
      0.77 (95% CI: 0.58, 0.89), a positive likelihood ratio of 0.94 (95% CI: 0.33,
      2.68), and a negative likelihood ratio of 1.02 (95% CI: 0.75, 1.38). CONCLUSION:
      Successful completion on pressure biofeedback does not indicate high TrA
      activation. Unsuccessful completion on pressure biofeedback may be more
      indicative of low TrA activation, but the correlation and likelihood coefficients
      indicate that the pressure test is likely of minimal value to detect TrA
      activation. This study was registered with ClinicalTrials.gov (NCT01015846).J
      Orthop Sports Phys Ther 2013;43(3):184-193. Epub 16 November 2012.
      doi:10.2519/jospt.2013.4397.

PMID- 23160345
TI  - Self-assembly of transition metal ion complexes of a hybrid pyrazine-terpyridine
      ligand.
AB  - A new hybrid pyrazine-terpyridine ligand L (C(34)H(22)N(8)) and its complexes
      with different transition metal ions, M (M = Mn(II) 1, Zn(II) 2, Fe(II) 3, Co(II)
      4, Cu(II) 5 and Cd(II) 6), have been synthesised. In the presence of a nitrate
      counter-anion, both Cu(II) and Cd(II) give complexes in which the ratio M:L is
      2:1, whereas with perchlorate, trifluoromethanesulfonate or tetrafluoroborate,
      the other metal ions provide solids in which this ratio is 1:1. From mass
      spectral measurements and a single crystal, X-ray structure determination for the
      Fe(II) complex 3, however, all the latter species are concluded to be 2:2
      complexes. Both the Fe(II) complex 3 and the Co(II) complex 4, generated from
      tetrafluoroborate reactant salts, have the composition
      [M(2)L(2)F(2)(H(2)O)](BF(4))(2), the presence of fluoride ligands being presumed
      to reflect the abstraction of fluoride ions from tetrafluoroborate by the metal
      ions under the preparative conditions. The crystal structure of complex 3 shows
      the Fe(II) centres to be inequivalent, one being high-spin and heptacoordinate
      with a FeN(4)F(2)O coordination sphere, the other low-spin and octahedral with a
      FeN(6) sphere. The two ligand molecules differ markedly, one being heptadentate,
      the other clearly "hypodentate", with only three N-donor atoms of a terpyridine
      like arm coordinated, although their conformations are similar, showing
      significant differences from that of C(2) symmetry found for the free ligand by a
      crystal structure determination. Mass spectra are consistent with the Cu(II) and
      Cd(II) complexes having the composition [M(2)L(H(2)O)(n)(NO(3))(4-n)](NO(3))(4
      n), and the weak antiferromagnetic coupling observed for the Cu(II) complex is
      consistent with a preliminary crystal structure determination which indicates
      that the two Cu(II) centres are not bridged by a pyrazine unit.

PMID- 23160346
TI  - The effect of urea on aqueous hydrophobic contact-pair interactions.
AB  - Urea is perhaps the most common denaturant used for studying proteins. However
      the mechanism of denaturation is still not well understood. Recent theoretical
      work suggests that van der Waals interactions between urea and non-polar amino
      acid residues are a major contributor to the protein denaturation process.
      However, there are few experimental data measuring the effect of urea on
      hydrophobic interactions. In this work we have determined how the addition of
      urea to the aqueous solvent affects the contact-pair formed between alkyl and
      phenyl groups in model compounds: the data indicate that for solutes having a
      radius smaller than 2.87 A cavity formation energetics dominate, therefore the
      addition of urea promotes the formation of hydrophobic contact pairs; while for
      larger solutes, van der Waals interactions have the largest magnitude, causing
      urea to disrupt the formation of contact pairs. The influence of urea on
      hydrophobic interactions is shown to be continuous in the 1-8 M concentration
      range and is well-correlated with the predictions of scaled particle theory. This
      demonstrates that the effect of urea on hydrophobic contact pairs can be
      explained by the changes observed in the solvent packing density, without having
      to invoke changes in the hydrogen bonding network of water.

PMID- 23160347
TI  - Sideline preparedness for the team physician:  a consensus statement-2012 update.

PMID- 23160348
TI  - The team physician and the return-to-play decision: a consensus statement-2012
      update.

PMID- 23160351
TI  - Polycomb PHF19 binds H3K36me3 and recruits PRC2 and demethylase NO66 to embryonic
      stem cell genes during differentiation.
AB  - Polycomb group proteins are repressive chromatin modifiers with essential roles
      in metazoan development, cellular differentiation and cell fate maintenance. How
      Polycomb proteins access active chromatin to confer transcriptional silencing
      during lineage transitions remains unclear. Here we show that the Polycomb
      repressive complex 2 (PRC2) component PHF19 binds trimethylated histone H3 Lys36
      (H3K36me3), a mark of active chromatin, via its Tudor domain. PHF19 associates
      with the H3K36me3 demethylase NO66, and it is required to recruit the PRC2
      complex and NO66 to stem cell genes during differentiation, leading to PRC2
      mediated trimethylation of histone H3 Lys27 (H3K27), loss of H3K36me3 and
      transcriptional silencing. We propose a model whereby PHF19 functions during
      mouse embryonic stem cell differentiation to transiently bind the H3K36me3 mark
      via its Tudor domain, forming essential contact points that allow recruitment of
      PRC2 and H3K36me3 demethylase activity to active gene loci during their
      transition to a Polycomb-repressed state.

PMID- 23160352
TI  - Hsp70 proteins bind Hsp100 regulatory M domains to activate AAA+ disaggregase at
      aggregate surfaces.
AB  - Bacteria, fungi and plants rescue aggregated proteins using a powerful
      bichaperone system composed of an Hsp70 chaperone and an Hsp100 AAA+
      disaggregase. In Escherichia coli, the Hsp70 chaperone DnaK binds aggregates and
      targets the disaggregase ClpB to the substrate. ClpB hexamers use ATP to thread
      substrate polypeptides through the central pore, driving disaggregation. How ClpB
      finds DnaK and regulates threading remains unclear. To dissect the disaggregation
      mechanism, we separated these steps using primarily chimeric ClpB-ClpV constructs
      that directly recognize alternative substrates, thereby obviating DnaK
      involvement. We show that ClpB has low intrinsic disaggregation activity that is
      normally repressed by the ClpB middle (M) domain. In the presence of aggregate,
      DnaK directly binds M-domain motif 2, increasing ClpB ATPase activity to unleash
      high ClpB threading power. Our results uncover a new function for Hsp70: the
      coupling of substrate targeting to AAA+ chaperone activation at aggregate
      surfaces.

PMID- 23160355
TI  - Epigenetics: a new link toward understanding human disease and drug response.
AB  - Molecular medicine is moving beyond genomics to encompass the new scientific
      field of epigenetics. First described as a conceptual model of how genes might
      interact with their surroundings to produce a phenotype, epigenomic research
      currently investigates mechanisms of nongenetic modification contributing to gene
      regulation and examines the impact of these changes on human health and behavior.

PMID- 23160353
TI  - A tightly regulated molecular toggle controls AAA+ disaggregase.
AB  - The ring-forming AAA+ protein ClpB cooperates with the DnaK chaperone system to
      refold aggregated proteins in Escherichia coli. The M domain, a ClpB-specific
      coiled-coil structure with two wings, motif 1 and motif 2, is essential to
      disaggregation, but the positioning and mechanistic role of M domains in ClpB
      hexamers remain unresolved. We show that M domains nestle at the ClpB ring
      surface, with both M-domain motifs contacting the first ATPase domain (AAA-1).
      Both wings contribute to maintaining a repressed ClpB activity state. Motif 2
      docks intramolecularly to AAA-1 to regulate ClpB unfolding power, and motif 1
      contacts a neighboring AAA-1 domain. Mutations that stabilize motif 2 docking
      repress ClpB, whereas destabilization leads to derepressed ClpB activity with
      greater unfolding power that is toxic in vivo. Our results underline the vital
      nature of tight ClpB activity control and elucidate a regulated M-domain toggle
      control mechanism.

PMID- 23160359
TI  - Resonant photoemission and spin polarization of Co(1-x)Fe(x)S(2).
AB  - The valence band occupied state electronic structure of Co(1-x)Fe(x)S(2) in the
      region of the Fe/Co 3d bands has been investigated using photoemission and spin
      polarized photoemission. As measured by using spin-polarized ultraviolet
      photoemission, the surface Fermi level spin polarization of Co(1-x)Fe(x)S(2) thin
      films at 50 K, specifically at x = 0, 0.05, 0.10 and 0.15, was found to be much
      reduced compared to that of the bulk. The spin polarization nonetheless increases
      with Fe concentration. The resonant photoemission spectroscopy provides evidence
      that S bands have a strong resonance at the photon energy corresponding to the Co
      2p core level, indicating strong hybridization between Co and S bands in Co(1
      x)Fe(x)S(2) (at small x). Similar evidence exists for Fe hybridization with the S
      bands.

PMID- 23160360
TI  - Yeast and fungal cell-wall polysaccharides can self-assemble in vitro into an
      ultrastructure resembling in vivo yeast cell walls.
AB  - Polysaccharides account for more than 90% of the content of fungal cell walls,
      but the mechanism underlying the formation of the architecture of the cell walls,
      which consist of microfibrils embedded in an amorphous wall matrix, remains
      unknown. We used electron microscopy to investigate ten different fungal cell
      wall polysaccharides to determine whether they could self-assemble into the
      fibrillar or amorphous component of fungal cell walls in a test tube without
      enzymes. The ultrastructures formed by precipitating beta-1,3-glucan and beta-1,6
      glucan are different depending on the existence of branching in the molecule.
      Linear beta-1,3-glucan and linear beta-1,6-glucan precipitate into a fibrillar
      ultrastructure. Branched beta-1,6-glucan, mannan and glycogen precipitates are
      amorphous. Branched beta-1,3-glucan forms a fibrillar plus amorphous
      ultrastructure. Self-assembly among combinations of different linear and branched
      cell-wall polysaccharides results in an ultrastructure that resembles that of a
      yeast cell wall, which suggests that self-assembly of polysaccharides may
      participate in the development of the three-dimensional architecture of the yeast
      cell wall.

PMID- 23160361
TI  - Performances of an 80-200 kV microscope employing a cold-FEG and an aberration
      corrected objective lens.
AB  - The performances of a newly developed 80-200 kV cold field emission gun (CFEG)
      transmission electron microscope (TEM) integrating a spherical aberration
      corrector for a TEM image-forming lens have been evaluated. To begin, we show
      that the stability of both emission and probe currents makes use of this new CFEG
      much friendlier. The energy spread of electrons emitted from the CFEG has been
      measured as a function of emission current and shows a very last 0.26 eV energy
      resolution at 200 kV and even 0.23 eV at 80 kV. The combination of the CFEG and
      the CEOSTM aberration corrector, associated with enhanced mechanical and
      electrical stabilities of this new microscope, allows reaching an information
      transfer below 75 pm at 200 and 80 pm at 80 kV. This unseen resolution at 200 kV
      has allowed us to study the structure of CoPt nanoparticles by observing direct
      images of their atomic arrangement along the high indexes zone axis. We have
      evidenced the presence of defects in these nanostructures that are not parallel
      to the electron beam. The precise stoichiometry of two iron oxides, FeO and
      Fe2O3, has been determined from an analysis of iron valence state that was
      obtained from a direct analysis of EELS fine structures spectrum of the two
      oxides.

PMID- 23160362
TI  - Flat ion milling: a powerful tool for preparation of cross-sections of lead
      silver alloys.
AB  - While conventional mechanical and chemical polishing results in stress,
      deformation and polishing particles embedded on the surface, flat milling with
      Ar+ ions erodes the material with no mechanical artefacts. This flat milling
      process is presented as an alternative method to prepare a Pb-Ag alloy cross
      section for scanning electron microscopy. The resulting surface is free of
      scratches with very little to no stress induced, so that electron diffraction and
      channelling contrast are possible. The results have shown that energy dispersive
      spectrometer (EDS) mapping, electron channelling contrast imaging and electron
      backscatter diffraction can be conducted with only one sample preparation step.
      Electron diffraction patterns acquired at 5 keV possessed very good pattern
      quality, highlighting an excellent surface condition. An orientation map was
      acquired at 20 keV with an indexing rate of 90.1%. An EDS map was performed at 5
      keV, and Pb-Ag precipitates of sizes lower than 100 nm were observed. However,
      the drawback of the method is the generation of a noticeable surface topography
      resulting from the interaction of the ion beam with a polycrystalline and
      biphasic sample.

PMID- 23160363
TI  - The effect of age-related differences in body size and composition on
      cardiovascular determinants of VO2max.
AB  - BACKGROUND: A reduction in maximal stroke volume (SVmax) and total blood volume
      (TBV) has been hypothesized to contribute to the decline in maximal oxygen uptake
      (VO2max) with healthy aging. However, these variables have rarely been collected
      simultaneously in a board age range to support or refute this hypothesis. It is
      also unclear to what extent scaling size-related cardiovascular determinants of
      VO2max affects the interpretation of age-related differences. METHODS: A
      retrospective analysis of VO2max, maximal cardiac output (QCmax), TBV, and body
      composition including fat-free mass (FFM) in 95 (51% M) healthy adults ranging
      from 19-86 years. RESULTS: Absolute and indexed VO2max, QCmax, and maximal heart
      rate decreased in both sexes with age (p <= .031). SVmax declined with age when
      scaled to total body mass or body surface area (p <= .047) but not when expressed
      in absolute levels (p = .120) or relative to FFM (p = .464). Absolute and indexed
      TBVs (mL/kg; mL/m(2)) were not significantly affected by age but increased with
      age in both sexes when scaled to FFM (p <= .013). A lower arteriovenous oxygen
      difference (a-vO2diff) contributed to the reduction in VO2max with age in
      treadmill exercisers (p = .004) but not in the entire cohort (p = .128).
      CONCLUSION: These results suggest (a) a reduction in absolute SVmax, and TBV do
      not contribute substantially to the age-related reduction in VO2max, which
      instead results from a smaller QCmax due to a lower maximal heart rate, and (b)
      body composition scaling methods should be used to accurately describe the effect
      of aging on physical function and cardiovascular variables.

PMID- 23160364
TI  - Depression treatment selectively modifies arterial stiffness in older
      participants.
AB  - BACKGROUND: Depression is emerging as an independent cardiovascular disease risk
      factor. We investigated whether treating depression in older participants
      impacted on arterial stiffness, a known cardiovascular disease risk factor and a
      clinical marker of arterial aging. METHODS: Seventy-five participants with pulse
      wave velocity (PWV), the gold standard measure for arterial stiffness, at
      baseline and at 12-month follow-up were included. Depressed patients were
      randomized to escitalopram (10mg/d) or to duloxetine (60mg/d). In patients
      without depression, no antidepressant therapy was started. The psychologist and
      the doctor measuring PWV were both unaware of antidepressant treatment. RESULTS:
      At study entry, no difference in PWV were observable in the three groups of
      participants. A significant time * drug interaction term (p < .05) was observed
      for the impact of antidepressant therapy on PWV by analysis of covariance
      analysis. After 12 months of therapy, duloxetine treatment resulted in a
      significant (+21%) and escitalopram treatment in a not significant (6%) PWV
      increase. These changes in PWV were accompanied by a similar increase in blood
      pressure and LDL cholesterol in the two treated groups. However, duloxetine
      resulted in a significant 10% greater heart rate after 12 months that was not
      observable in participants treated with escitalopram nor in not-depressed older
      participants. Multiple regression models revealed that a drug-specific effect on
      PWV persisted after controlling for cardiovascular risk factor levels.
      CONCLUSION: Duloxetine but not escitalopram significantly increased PWV in older
      depressed participants after 12 months of treatment. The effect was not fully
      explained by concomitant changes in traditional cardiovascular risk factors known
      to significantly impact arterial stiffness.

PMID- 23160365
TI  - Pleiotropy and life history evolution in Drosophila melanogaster: uncoupling life
      span and early fecundity.
AB  - Populations of Drosophila melanogaster that have been artificially selected for
      late age of reproduction evolve longer life spans and, in some cases, reduced
      early fecundity. The negative correlation is widely interpreted as evidence of
      antagonistic pleiotropy. Here, we show that the correlation breaks down in
      recombinant genomes. A major quantitative trait locus that increases adult life
      span by 20% has no detectable effect on early fecundity. Several recombinant
      genotypes are superflies, exhibiting both elevated early fecundity and long life.
      The genetic correlation of early fecundity and life span is not different from
      zero, while the midlife fecundity correlation is positive and statistically
      significant, suggesting age-specific adaptation. The results are not consistent
      with a dominant role for negative pleiotropy, but can be understood in terms of a
      mixture of pleiotropic and recombining nonpleiotropic elements. Life span and
      early fecundity can be genetically uncoupled.

PMID- 23160366
TI  - Candidate gene association study of BMI-related loci, weight, and adiposity in
      old age.
AB  - Most genome-wide association studies are confined to middle-aged populations. It
      is unclear whether associations between single nucleotide polymorphisms (SNPs)
      and obesity persist in old age. We aimed to relate 10 body mass index (BMI)
      associated SNPs to weight, BMI, % fat, visceral and subcutaneous adipose tissue
      in Health ABC and AGES-Reykjavik comprising 4,846 individuals of European
      Ancestry, and 1,139 African Americans over age 65. SNPs were scaled using effect
      estimates from candidate SNPs. In Health ABC, a SNP near GNPDA2 was modestly
      associated with weight and SAT area (p = .008, p = .001). Risk score (sum of
      scaled SNPs) was associated with weight, BMI, and SAT area (p < .0001 for all),
      but neither GNPDA2 nor risk score was associated with weight, BMI, visceral
      adippose tissue, subcutaneous adipose tissue, or % fat in AGES-Reykjavik. In
      African Americans, a SNP near SEC16B was weakly associated with weight (p = .04).
      In this sample of older adults, no BMI-associated SNPs were associated with
      weight or adiposity.

PMID- 23160367
TI  - Long-term trajectories of lower extremity function in older adults: estimating
      gender differences while accounting for potential mortality bias.
AB  - BACKGROUND: Gender-specific trajectories of lower extremity function (LEF) and
      the potential for bias in LEF estimation due to differences in survival have been
      understudied. METHODS: We evaluated longitudinal data from 690 initially
      nondisabled adults age 70 or older from the Precipitating Events Project. LEF was
      assessed every 18 months for 12 years using a modified Short Physical Performance
      Battery (mSPPB). Hierarchical linear models with adjustments for length-of
      survival estimated the intraindividual trajectory of LEF and differences in
      trajectory intercept and slope between men and women. RESULTS: LEF declined
      following a nonlinear trajectory. In the full sample, and among participants with
      high (mSPPB 10-12) and intermediate (mSPPB 7-9) baseline LEF, the rate-of-decline
      in mSPPB was slower in women than in men, with no gender differences in baseline
      mSPPB scores. Among participants with low baseline LEF (mSPPB <=6), men had a
      higher starting mSPPB score, whereas women experienced a deceleration in the rate
      of-decline over time. In all groups, participants who survived longer had higher
      starting mSPPB scores and slower rates-of-decline compared with those who died
      sooner. CONCLUSIONS: Over the course of 12 years, older women preserve LEF better
      than men. Nonadjustment for differences in survival results in overestimating the
      level and underestimating the rate-of-decline in LEF over time.

PMID- 23160368
TI  - Comparison of the sonographic features of the abdominal wall muscles and
      connective tissues in individuals with and without lumbopelvic pain.
AB  - STUDY DESIGN: Cross-sectional, case-control study. OBJECTIVES: To measure and
      compare the resting thickness of the 4 abdominal wall muscles, their associated
      perimuscular connective tissue (PMCT), and interrecti distance (IRD) in persons
      with and without lumbopelvic pain (LPP), using ultrasound imaging. BACKGROUND:
      The muscles and PMCT of the abdominal wall assist in controlling the spine.
      Functional deficits of the abdominal wall muscles have been detected in
      populations with LPP. Investigations of the abdominal wall in those with LPP are
      primarily concerned with muscle, most commonly the transversus abdominis (TrA)
      and internal oblique (IO). Because the abdominal wall functions as a unit, all 4
      abdominal muscles and their associated connective tissues should be considered
      concurrently. METHODS: B-mode ultrasound imaging was used to measure the resting
      thickness of the rectus abdominis (RA), external oblique, IO, and TrA muscles;
      the PMCT planes; and IRD in 50 male and female subjects, 25 with and 25 without
      LPP (mean +/- SD age, 36.3 +/- 9.4 and 46.6 +/- 8.0 years, respectively).
      Univariate correlation analysis was used to identify covariates. Analyses of
      covariance (ANCOVAs) and the Kruskal-Wallis test (IRD) were used to compare
      cohorts (alpha = .05). RESULTS: The LPP cohort had less total abdominal muscle
      thickness (LPP mean +/- SD, 18.9 +/- 3.0 mm; control, 20.3 +/- 3.0 mm; ANCOVA
      adjusted for body mass index, P = .03), thicker PMCT (LPP, 5.5 +/- 0.2 mm;
      control, 4.3 +/- 0.2 mm; ANCOVA adjusted for body mass index, P = .007), and
      wider IRD (LPP, 11.5 +/- 2.0 mm; control, 8.4 +/- 1.8 mm; Kruskal-Wallis, P =
      .005). Analysis of individual muscle thickness revealed no difference in the
      external oblique, IO, and TrA, but a thinner RA in the LPP cohort (LPP mean +/-
      SD, 7.8 +/- 1.5 mm; control, 9.1 +/- 1.2 mm; ANCOVA adjusted for body mass index,
      P<.001). CONCLUSION: To our knowledge, this is the first study to investigate the
      morphological characteristics of all 4 abdominal muscles and PMCT in individuals
      with LPP. The results suggest that there may be altered loading of the PMCT and
      linea alba secondary to an altered motor control strategy involving a reduced
      contribution of the RA. Further, the change in RA and connective tissue
      morphology may be more evident than changes in external oblique, IO, and TrA
      thickness in persons with LPP. The causes and functional implications of these
      changes warrant further investigation, as does the role of the RA muscle in the
      development and persistence of LPP.

PMID- 23160369
TI  - Graphene oxide as a promising photocatalyst for CO2 to methanol conversion.
AB  - Photocatalytic conversion of carbon dioxide (CO(2)) to hydrocarbons such as
      methanol makes possible simultaneous solar energy harvesting and CO(2) reduction,
      two birds with one stone for the energy and environmental issues. This work
      describes a high photocatalytic conversion of CO(2) to methanol using graphene
      oxides (GOs) as a promising photocatalyst. The modified Hummer's method has been
      applied to synthesize the GO based photocatalyst for the enhanced catalytic
      activity. The photocatalytic CO(2) to methanol conversion rate on modified
      graphene oxide (GO-3) is 0.172 MUmol g cat(-1) h(-1) under visible light, which
      is six-fold higher than the pure TiO(2).

PMID- 23160371
TI  - YAP1 oncogene and its eight isoforms.

PMID- 23160370
TI  - The neural guidance receptor Plexin C1 delays melanoma progression.
AB  - Plexin C1 is a type I transmembrane receptor with intrinsic R-Ras GTPase
      activity, which regulates cytoskeletal remodeling and adhesion in normal human
      melanocytes. Melanocytes are pigment-producing cells of the epidermis, precursors
      for melanoma, and express high levels of Plexin C1, which is lost in melanoma in
      vitro and in vivo. To determine if Plexin C1 is a tumor suppressor for melanoma,
      we introduced Plexin C1 into a primary human melanoma cell line, and phenotypes
      including migration, apoptosis, proliferation and tumor growth in mice were
      analyzed. Complimentary studies in which Plexin C1 was silenced in human
      melanocytes were performed. Plexin C1 significantly inhibited migration and
      proliferation in melanoma, whereas in melanocytes, loss of Plexin C1 increased
      migration and proliferation. In mouse xenografts, Plexin C1 delayed tumor growth
      of melanoma at early time points, but tumors eventually escaped the suppressive
      effects of Plexin C1, due to Plexin C1-dependent activation of the pro-survival
      protein Akt. R-Ras activation stimulates melanoma migration. Plexin C1 lowered R
      Ras activity in melanoma and melanocytes, consistent with inhibitory effects of
      Plexin C1 on migration of melanocytes and melanoma. To determine if R-Ras is
      expressed in melanocytic lesions in vivo, staining of tissue microarrays of nevi
      and melanoma were performed. R-Ras expression was highly limited in melanocytic
      lesions, being essentially confined to primary melanoma, and almost completely
      absent in nevi and metastatic melanoma. These data suggest that loss of Plexin C1
      in melanoma may promote early steps in melanoma progression through suppression
      of migration and proliferation, but pro-survival effects of Plexin C1 ultimately
      abrogate the tumor suppressive effects of Plexin C1. In primary melanoma, loss of
      Plexin C1 may function in early steps of melanoma progression by releasing
      inhibition of R-Ras activation, and stimulating migration.

PMID- 23160373
TI  - The growing complexity of HIF-1alpha's role in tumorigenesis: DNA repair and
      beyond.
AB  - Lack of oxygen (hypoxia) is a central hallmark of cancer and a pivotal driving
      force of malignant progression. Transcriptional activators of the hypoxia
      inducible factor alpha (HIFalpha) family represent the principal molecular
      mediators of hypoxia under both physiological and pathophysiological conditions.
      While HIF-2alpha is expressed in a tissue- and cell-type-restricted manner,
      stabilization of HIF-1alpha was reported in tumours of widely different origin,
      and functional analyses led to the perception of HIF-1alpha as an oncoprotein. In
      this review, we aim to acknowledge HIFalpha's growing complexity by outlining its
      functional relevance for genomic integrity and tumour heterogeneity, two features
      of paramount importance for basic and clinical oncology. Pharmaceutical companies
      around the globe are ambitiously hunting for HIF-1alpha-inhibiting compounds,
      some of which are currently being evaluated in phase 1 trials. To avoid the
      rather disappointing clinical efficacy emblematic of most targeted therapeutics,
      potential resistance mechanisms of, as well as potential combination partners
      for, HIF-1alpha-inhibiting drugs should be evaluated. In this regard, the
      interrelation of HIF-1alpha with genomic integrity and tumour heterogeneity
      offers ample possibilities, potentially resulting in more efficient clinical
      translation of HIF-1alpha's pathobiology. 

PMID- 23160372
TI  - Targeting genetic alterations in protein methyltransferases for personalized
      cancer therapeutics.
AB  - The human protein methyltransferases (PMTs) constitute a large enzyme class
      composed of two families, the protein lysine methyltransferases (PKMTs) and the
      protein arginine methyltransferases (PRMTs). Examples have been reported of both
      PKMTs and PRMTs that are genetically altered in specific human cancers, and in
      several cases these alterations have been demonstrated to confer a unique
      dependence of the cancer cells on PMT enzymatic activity for the tumorigenic
      phenotype. Examples of such driver alterations in PMTs will be presented together
      with a review of current efforts towards the discovery and development of small
      molecule inhibitors of these enzymes as personalized cancer therapeutics.

PMID- 23160374
TI  - CLOCK is a substrate of SUMO and sumoylation of CLOCK upregulates the
      transcriptional activity of estrogen receptor-alpha.
AB  - Disruption of the circadian rhythm is now believed to associate with a number of
      hormone-related cancers, such as breast cancer, in which aberrant estrogen
      receptor-alpha (ERalpha) signaling is a major contributor. However, the molecular
      mechanisms underlying the function of core clock proteins in cancer are still
      largely undefined. In this study, we showed that circadian locomotor output
      cycles kaput (CLOCK), a key circadian protein, can interact with ERalpha.
      Furthermore, this interaction was enhanced by estrogen. We also showed that CLOCK
      can be sumoylated and sumoylation of CLOCK, which is also stimulated by estrogen,
      had two consequences: (1) it increased the transcriptional activity of CLOCK; and
      (2) it increased the CLOCK-modulated transcriptional activity of ERalpha, as
      shown by increased transcription of cyclin D1. Sumoylation of CLOCK occurred at
      two lysine residues, K67 and K851. The enhancement of ERalpha transcriptional
      activity exerted by wild-type but not mutant (2K/2R) CLOCK in response to
      estrogen indicated that sumoylation of CLOCK may have an important role in
      estrogen-dependent signaling. 3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide (MTT) assay conducted with breast cancer cell lines
      (MCF-7 and T47D) demonstrated that sumoylation of CLOCK stimulated cell growth
      and increased the proportion of S phase cells in the cell cycle. The results of
      this study uncovered new insight into the connection between a major circadian
      protein and a major estrogen-dependent transcription factor, providing the basis
      for further research into the involvement of circadian proteins in breast cancer.

PMID- 23160377
TI  - Doxorubicin promotes transcriptional upregulation of Cdc25B in cancer cells by
      releasing Sp1 from the promoter.
AB  - Cdc25B phosphatases have a key role in G2/M cell-cycle progression by activating
      the CDK1-cyclinB1 complexes and functioning as important targets of checkpoints.
      Overexpression of Cdc25B results in a bypass of the G2/M checkpoint and
      illegitimate entry into mitosis. It can also cause replicative stress, which
      leads to genomic instability. Thus, fine-tuning of the Cdc25B expression level is
      critical for correct cell-cycle arrest in response to DNA damage. In response to
      genotoxic stress, Cdc25B is mainly regulated by post-transcriptional mechanisms
      affecting either Cdc25B protein stability or translation. Here, we show that upon
      DNA damage Cdc25B can be regulated at the transcriptional level. Although
      ionizing radiation downregulates Cdc25B in a p53-dependent pathway, doxorubicin
      transcriptionally upregulates Cdc25B in p53-proficient cancer cells. We show that
      in the presence of wild-type p53, doxorubicin activates the Cdc25B promoter by
      preventing the binding of Sp1 and increasing the binding of NF-Y on the Cdc25B
      promoter, thus preventing p53 from downregulating this promoter. Our results
      highlight the mechanistically distinct regulation of the three Cdc25 phosphatases
      by checkpoint signalling following doxorubicin treatment. 

PMID- 23160375
TI  - A novel approach to biomarker discovery in head and neck cancer using an
      autoantibody signature.
AB  - Despite the dismal prognosis for patients with squamous cell carcinoma of the
      head and neck (SCCHN), there have been no novel treatments in over 40 years.
      Identification of novel tumor antigens in SCCHN will facilitate the
      identification of potential novel treatment targets. Tumor antigens are proteins
      selectively expressed by tumor cells and recognized by the host immune system.
      Phage-displayed tumor antigens were enriched by biopanning with normal and then
      SCCHN-specific serum. Ninety-six phage clones were sequenced for identification,
      and 21 clones were validated using Luminex. One of these proteins, L23, a novel
      tumor antigen in SCCHN, was validated as an oncogene. L23 is upregulated in SCCHN
      compared with normal keratinocytes. Knockdown of L23 inhibited proliferation,
      invasion and cell survival. Overexpression of L23 had the reverse effect.
      Overexpression of L23 in non malignant cells led to transformation. Injection of
      SCCHN cells with knockdown of L23 in mice, induced tumors that were significantly
      smaller than control tumors. In conclusion, the immunomic screen yielded a panel
      of antigens specific to SCCHN; one of these proteins, L23, is a novel oncogene in
      SCCHN. 

PMID- 23160376
TI  - Transcriptional intermediary factor 1gamma binds to the anaphase-promoting
      complex/cyclosome and promotes mitosis.
AB  - The anaphase-promoting complex/cyclosome (APC/C) is an ubiquitin ligase that
      functions during mitosis. Here we identify the transcriptional regulator,
      transcriptional intermediary factor 1gamma, TIF1gamma, as an APC/C-interacting
      protein that regulates APC/C function. TIF1gamma is not a substrate for APC/C
      dependent ubiquitylation but instead, associates specifically with the APC/C
      holoenzyme and Cdc20 to affect APC/C activity and progression through mitosis.
      RNA interference studies indicate that TIF1gamma knockdown results in a specific
      reduction in APC/C ubiquitin ligase activity, the stabilization of APC/C
      substrates, and an increase in the time taken for cells to progress through
      mitosis from nuclear envelope breakdown to anaphase. TIF1gamma knockdown cells
      are also characterized by the inappropriate presence of cyclin A at metaphase,
      and an increase in the number of cells that fail to undergo metaphase-to-anaphase
      transition. Expression of a small interfering RNA-resistant TIF1gamma species
      relieves the mitotic phenotype imposed by TIF1gamma knockdown and allows for
      mitotic progression. Binding studies indicate that TIF1gamma is also a component
      of the APC/C-mitotic checkpoint complex (MCC), but is not required for MCC
      dissociation from the APC/C once the spindle assembly checkpoint (SAC) is
      satisfied. TIF1gamma inactivation also results in chromosome misalignment at
      metaphase and SAC activation; inactivation of the SAC relieves the mitotic block
      imposed by TIF1gamma knockdown. Together these data define novel functions for
      TIF1gamma during mitosis and suggest that a reduction in APC/C ubiquitin ligase
      activity promotes SAC activation. 

PMID- 23160378
TI  - YB-1 (YBX1) does not bind to Y/CCAAT boxes in vivo.

PMID- 23160379
TI  - Claudin-1 induces epithelial-mesenchymal transition through activation of the c
      Abl-ERK signaling pathway in human liver cells.
AB  - Claudins (CLDNs) are a family of integral membrane proteins central to the
      formation of tight junctions, structures that are involved in paracellular
      transport and cellular growth and differentiation, and are critical for the
      maintenance of cellular polarity. Recent studies have provided evidence that
      CLDNs are aberrantly expressed in diverse types of human cancers, including
      hepatocellular carcinomas (HCCs). However, little is known about how CLDN
      expression is involved in cancer progression. In this study, we show that CLDN1
      has a causal role in the epithelial-mesenchymal transition (EMT) in human liver
      cells, and that the c-Abl-Ras-Raf-1-ERK1/2 signaling axis is critical for the
      induction of malignant progression by CLDN1. Overexpression of CLDN1 induced
      expression of the EMT-regulating transcription factors Slug and Zeb1, and thereby
      led to repression of E-cadherin, beta-catenin expression, enhanced expression of
      N-cadherin and Vimentin, a loss of cell adhesion, and increased cell motility in
      normal liver cells and HCC cells. In line with these findings, inhibition of
      either c-Abl or ERK clearly attenuated CLDN1-induced EMT, as evidenced by a
      reversal of N-cadherin and E-cadherin expression patterns, and restored normal
      motility. Collectively, these results indicate that CLDN1 is necessary for the
      induction of EMT in human liver cells, and that activation of the c-Abl-Ras-Raf-1
      ERK1/2 signaling pathway is required for CLDN1-induced acquisition of the
      malignant phenotype. The present observations suggest that CLDN1 could be
      exploited as a biomarker for liver cancer metastasis and might provide a pivotal
      point for therapeutic intervention in HCC.

PMID- 23160380
TI  - Regulation of autophagy during ECM detachment is linked to a selective inhibition
      of mTORC1 by PERK.
AB  - Adhesion to the extracellular matrix (ECM) is critical for epithelial tissue
      homeostasis and function. ECM detachment induces metabolic stress and programmed
      cell death via anoikis. ECM-detached mammary epithelial cells are able to rapidly
      activate autophagy allowing for survival and an opportunity for re-attachment.
      However, the mechanisms controlling detachment-induced autophagy remain unclear.
      Here we uncover that the kinase PERK rapidly promotes autophagy in ECM-detached
      cells by activating AMP-activated protein kinase (AMPK), resulting in downstream
      inhibition of mTORC1-p70(S6K) signaling. LKB1 and TSC2, but not TSC1, are
      required for PERK-mediated inhibition of mammalian target of rapamycinin MCF10A
      cells and mouse embryo fibroblast cells. Importantly, this pathway shows fast
      kinetics, is transcription-independent and is exclusively activated during ECM
      detachment, but not by canonical endoplasmic reticulum stressors. Moreover,
      enforced PERK or AMPK activation upregulates autophagy and causes luminal filling
      during acinar morphogenesis by perpetuating a population of surviving autophagic
      luminal cells that resist anoikis. Hence, we identify a novel pathway in which
      suspension-activated PERK promotes the activation of LKB1, AMPK and TSC2, leading
      to the rapid induction of detachment-induced autophagy. We propose that increased
      autophagy, secondary to persistent PERK and LKB1-AMPK signaling, can robustly
      protect cells from anoikis and promote luminal filling during early carcinoma
      progression.

PMID- 23160381
TI  - Galectin-3 regulates p21 stability in human prostate cancer cells.
AB  - Galectin-3 (Gal-3) is a multifunctional protein involved in cancer through
      regulation of cell adhesion, cell growth, apoptosis and metastasis, while p21
      (Cip1/WAF1) is a negative regulator of the cell cycle, involved in apoptosis,
      transcription, DNA repair and metastasis. The results presented here demonstrate
      for the first time that the level of Gal-3 protein is associated with the level
      of p21 protein expression in human prostate cancer cells and the effects of Gal-3
      on cell growth and apoptosis were reversed by modulating p21 expression level.
      Furthermore, Gal-3 regulates p21 expression at the post-translational level by
      stabilizing p21 protein via the carbohydrate-recognition domain. This is the
      first report suggesting a molecular function not yet described for Gal-3 as the
      regulator of p21 protein stability. This study provides a unique insight into the
      relationship of these two molecules during prostate cancer progression, and may
      provide a novel therapeutic target. 

PMID- 23160382
TI  - The protective role of pomegranate juice against carbon tetrachloride-induced
      oxidative stress in rats.
AB  - Most pomegranate (Punica granatum Linn., Punicaceae) fruit parts are known to
      possess enormous antioxidant activity. The present study was carried out to
      determine the phenolic and flavonoid contents of Derik pomegranate juice and
      determine its effect against carbon tetrachloride (CCl4)-induced toxicity in
      rats. Animals were divided into four groups (n = 6): group I: control, group II:
      CCl4 (1 ml/kg), group III: CCl4 + pomegranate juice and group IV: CCl4 +
      ursodeoxycholic acid (UDCA). Treatment duration was 4 weeks, and the dose of CCl4
      was administered once a week to groups II, III and IV during the experimental
      period. CCl4-treated rats caused a significant increase in serum enzyme levels,
      such as aspartate aminotransferase, alanine aminotransferase and total bilirubin,
      and decrease in albumin, when compared with control. Administration of CCl4 along
      with pomegranate juice or UDCA significantly reduces these changes. Analysis of
      lipid peroxide (LPO) levels by thiobarbutiric acid reaction showed a significant
      increase in liver, kidney and brain tissues of CCl4-treated rats. However, both
      pomegranate juice and UDCA prevented the increase in LPO level. Histopathological
      reports also revealed that there is a regenerative activity in the liver and
      kidney cells. Derik pomegranate juice showed to be hepatoprotective against CCl4
      induced hepatic injury. In conclusion, present study reveals a biological
      evidence that supports the use of pomegranate juice in the treatment of chemical
      induced hepatotoxicity. 

PMID- 23160383
TI  - Selenium pretreatment attenuates formaldehyde-induced genotoxicity in A549 cell
      lines.
AB  - Formaldehyde is a major industrial chemical and has been extensively used in the
      manufacture of synthetic resins and chemicals. Numerous studies indicate that
      formaldehyde can induce various genotoxic effects in vitro and in vivo. A recent
      study indicated that formaldehyde impaired antioxidant cellular defences and
      enhanced lipid peroxidation. Selenium is an important antioxidant. We
      hypothesized that reactive oxygen species (ROS) and lipid peroxidation are
      involved in formaldehyde-induced genotoxicity in human lung cancer cell line,
      A549 cell line. To test the hypothesis, we investigated the effects of selenium
      on formaldehyde-induced genotoxicity in A549 cell lines. The results indicated
      that exposure to formaldehyde showed the induction of DNA-protein cross-links
      (DPCs). Formaldehyde significantly increased the malondialdehyde levels and
      decreased the activities of superoxide dismutase and glutathione peroxidase. In
      addition, the activations of necrosis factor-kappaB (NF-kappaB) and activator
      protein 1 (AP-1) were induced by the formaldehyde treatment. The pretreatment
      with selenium counteracted the formaldehyde-induced oxidative stress, ameliorated
      DPCs and attenuated the activation of NF-kappaB and AP-1 in A549 cell lines. All
      the results suggested that the pretreatment with selenium attenuated the
      formaldehyde-induced genotoxicity through its ROS scavenging and anti-DPCs
      effects in A549 cell lines. 

PMID- 23160384
TI  - Beneficial role of celery oil in lowering the di(2-ethylhexyl) phthalate-induced
      testicular damage.
AB  - Di(2-ethylhexyl) phthalate (DEHP), the most abundant phthalate in the
      environment, is known to be a reproductive toxicant. Considering the therapeutic
      significance of medicinal plants, this study was conducted to evaluate the
      effects of administration of celery oil on DEHP-induced testicular toxicity. The
      experiment was carried out for 8 weeks on 36 male rats that were divided equally
      into six groups. Group 1 was kept as normal control (given vehicle), while rats
      of group 2 were administered orally 200 mg/kg/day of celery oil. Groups 3 and 5
      were orally given 500 and 1000 mg DEHP/kg/day, respectively. Groups 4 and 6 were
      treated with similar doses of DEHP as in groups 3 and 5 plus celery oil (200
      mg/kg/day). Body and testicular weights, sperm parameters, serum hormones
      (testosterone, follicle-stimulating hormone, luteinizing hormone and estradiol),
      antioxidant enzymes (superoxide dismutase (SOD), glutathione peroxidase (GPx) and
      catalase (CAT)) and expression of cytochrome P450 aromatase (CYP19) messenger RNA
      (mRNA) were investigated at the end of 8th week. Treatment with DEHP alone
      resulted in a significant decrease in body and testicular weights, sperm
      parameters and serum hormone levels when compared with control. On the other
      hand, testicular antioxidant enzymes showed a significant dose-dependent
      increase. The expression of CYP19 mRNA was significantly reduced by increasing
      the doses of DEHP. Administration of celery oil along with DEHP partially
      prevented the decrease in body and testicular weights and enhanced epididymal
      sperm count, serum hormone levels and the expression of CYP19 mRNA along with
      diminution in the activities of SOD, GPx and CAT enzymes. The obtained results
      showed that the celery improved the testicular alterations induced by DEHP in
      albino rats.

PMID- 23160385
TI  - Granulocytic myeloid-derived suppressor cells are cryosensitive and their
      frequency does not correlate with serum concentrations of colony-stimulating
      factors in head and neck cancer.
AB  - Granulocytic myeloid-derived suppressor cells (MDSC) are a MDSC subset expanded
      in various cancer types. As many clinical studies rely on the use of stored
      collections of frozen blood samples, we first tested the influence of
      freezing/thawing procedures on immunophenotyping and enumeration of granulocytic
      MDSC (G-MDSC). To identify factors involved in expansion of human G-MDSC, we then
      analyzed correlations between G-MDSC frequencies, clinical parameters and
      granulocyte-related factors in the peripheral blood of head and neck cancer
      patients. HLA-DR, CD14, CD33 and CD66b allowed a clear discrimination of G-MDSC
      from monocytic MDSC and immature myeloid cells. MDSC subsets were sensitive to
      cryopreservation with immature G-MDSC showing the highest sensitivity. G-MDSC
      frequencies were increased in advanced disease stage and associated with the
      level of CCL4 and CXCL8, but not with colony-stimulating factors, IL-6, S100A8/9,
      CXCL1 and other cytokines. Our results indicate that the frequency of MDSC, in
      particular G-MDSC, may be underestimated in retrospective clinical analyses using
      frozen blood samples. Increased G-MDSC frequencies correlate with advanced
      disease and increased concentrations of CXCL8, but, unexpectedly, not with growth
      factors (such as granulocyte colony-stimulating factor), IL-6 and CXCL1. Our data
      suggest that CXCL8 promotes accumulation of G-MDSC in cancer patients independent
      of classical colony-stimulating factors.

PMID- 23160386
TI  - Bactericidal/permeability increasing protein: a multifaceted protein with
      functions beyond LPS neutralization.
AB  - Bactericidal permeability increasing protein (BPI), a 55-60 kDa protein, first
      reported in 1975, has gone a long way as a protein with multifunctional roles.
      Its classical role in neutralizing endotoxin (LPS) raised high hopes among septic
      shock patients. Today, BPI is not just a LPS-neutralizing protein, but a protein
      with diverse functions. These functions can be as varied as inhibition of
      endothelial cell growth and inhibition of dendritic cell maturation, or as an
      anti-angiogenic, chemoattractant or opsonization agent. Though the literature
      available is extremely limited, it is fascinating to look into how BPI is gaining
      major importance as a signalling molecule. In this review, we briefly summarize
      the recent research focused on the multiple roles of BPI and its use as a
      therapeutic. 

PMID- 23160387
TI  - Antimicrobial peptide elicitors: new hope for the post-antibiotic era.
AB  - Antimicrobial peptides or host defense peptides are fundamental components of
      human innate immunity. Recent and growing evidence suggests they have a role in a
      broad range of diseases, including cancer, allergies and susceptibility to
      infection, including HIV/AIDS. Antimicrobial peptide elicitors (APEs) are
      physical, biological or chemical agents that boost human antimicrobial peptide
      expression. The current knowledge of APEs and their potential use in the
      treatment of human infectious diseases are reviewed, and a classification system
      for APEs is proposed. The efficient use of APEs in clinical practice could mark
      the beginning of the urgently needed post-antibiotic era, but further trials
      assessing their efficacy and safety are required.

PMID- 23160390
TI  - Endovascular therapy with MCP-1 releasing coils promotes inflammatory intra
      aneurysmal tissue healing.

PMID- 23160391
TI  - Circuitry of the adult hippocampal neural stem cell niche.

PMID- 23160392
TI  - Neural stem cell grafts for complete spinal cord injury.

PMID- 23160393
TI  - Bridging the generations for successful neurosurgery practice.

PMID- 23160394
TI  - Bypassing the spinal cord:  functional electrical stimulation guided by
      electrocorticography decoding.

PMID- 23160395
TI  - How can simulation thrive as an educational tool? Just ask the residents.

PMID- 23160396
TI  - Trials and tribulations of cancer immunotherapy:  the dendritic cell vaccine
      shows promise in a phase I glioblastoma multiforme trial.

PMID- 23160397
TI  - Granulocyte-stimulating colony factor neuroprotection for thoracic myelopathy.

PMID- 23160398
TI  - The role of cyclin-d2 in the tumorgenesis of glioblastoma.

PMID- 23160399
TI  - Harnessing the brain's tools for killing cancer cells could be a key to treating
      high-grade gliomas.

PMID- 23160400
TI  - Novel anti-inflammatory strategies in atherosclerosis.
AB  - PURPOSE OF REVIEW: Inflammation has been widely acknowledged to contribute
      throughout all stages of atherogenesis. However, these recent advances in our
      understanding have not been translated into clinical practice in which the
      mainstay of treatment is still lipid-targeted therapy. This review provides an
      overview of promising anti-inflammatory therapies in atherosclerosis, and
      discusses potential drawbacks and clinical benefits. RECENT FINDINGS:
      Immunosuppressive drugs are likely to beneficially affect atherogenesis. Several
      novel anti-inflammatory targets have been scrutinized, of which some have reached
      clinical development stage, such as cytokine targets interleukin-1 and
      interleukin-6, CCR2 antagonist, selective phospholipase, and leukotriene
      inhibitors. Novel imaging modalities such as MRI and PET-computed tomography
      provide valuable surrogate inflammatory endpoints for risk stratification and
      testing anti-inflammatory agents in cardiovascular randomized trials. SUMMARY:
      Anti-inflammatory therapies hold great promise in cardiovascular prevention
      regimens; however, atherosclerosis is a chronic disease, and systemic long-term
      use of anti-inflammatory agents carries the risk of complications arising from
      immunosuppression. In order to successfully add immunosuppressive drugs to our
      routine armament, we need to identify high-risk patients who benefit from anti
      inflammatory treatment, increase our insight into the inflammatory pathogenesis
      of atherogenesis, and find safe and effective compounds capable of directly
      suppressing plaque inflammation.

PMID- 23160401
TI  - Cardiovascular protective properties of incretin-based therapies in type 2
      diabetes.
AB  - PURPOSE OF REVIEW: Type 2 diabetes mellitus is a chronic dysmetabolic condition
      characterized by hyperglycemia and accompanied by dyslipidemia (low HDL, high
      triglycerides), and hypertension associated with insulin resistance in obesity.
      In addition to the glucose-reducing effects, incretin-based therapies have been
      found to have cardiovascular protective properties. This review summarizes the
      best available evidence favoring these positive pleiotropic effects of incretin
      mimetics as well as incretin enhancers. RECENT FINDINGS: Studies in animals and
      humans are accumulating showing the direct as well as indirect actions of the
      glucagon-like peptide 1 analogues and dipeptidyl peptidase 4 inhibitors on the
      cardiovascular system. This class of agents appear to have effects on the
      cardiomyocytes, blood vessels, adipose tissue, regulation of blood pressure, and
      postprandial intestinal lipoprotein metabolism. SUMMARY: Long-term hard outcome
      trials are under way that investigate the effects of incretin-based treatments on
      elevated cardiovascular risks in patients with type 2 diabetes.

PMID- 23160402
TI  - Current world literature.

PMID- 23160403
TI  - Lipid-protein interactions:  finding the perfect match.

PMID- 23160404
TI  - Lipid metabolism:  thyroid hormone effects on lipid metabolism.

PMID- 23160405
TI  - Paternal transmission, cardiovascular risk factors and epigenetics.

PMID- 23160406
TI  - Limitation of myocardial ischemia-reperfusion injury in clinical practice:  new
      hopes and disappointments.

PMID- 23160407
TI  - Hyperlipidemia and cardiovascular disease.

PMID- 23160409
TI  - Phase behavior of mixed Ar-Kr, Ar-Xe and Kr-Xe monolayer films on graphite: a
      Monte Carlo study.
AB  - Using Monte Carlo simulation methods in the grand canonical ensemble we have
      studied the behavior of mixed Ar-Kr, Ar-Xe and Kr-Xe monolayer films on the
      graphite basal plane. We have considered the adsorption of the lighter component,
      either argon or krypton, under the condition of a fixed chemical potential of the
      heavier component (krypton or xenon), as well as on the graphite surface with
      preadsorbed small amounts of a heavier noble gas. In both types of simulation the
      composition of the adsorbed layer is not conserved. We discuss the phase behavior
      of mixed films emerging from both types of 'computer experiment'. We also
      demonstrate that Monte Carlo simulation allows us to estimate the effects of
      preadsorbed xenon on the commensurate-incommensurate transition in the krypton
      monolayer film and gives the results that are in good quantitative agreement with
      experimental data.

PMID- 23160411
TI  - Developing a biocuration workflow for AgBase, a non-model organism database.
AB  - AgBase provides annotation for agricultural gene products using the Gene Ontology
      (GO) and Plant Ontology, as appropriate. Unlike model organism species,
      agricultural species have a body of literature that does not just focus on gene
      function; to improve efficiency, we use text mining to identify literature for
      curation. The first component of our annotation interface is the gene
      prioritization interface that ranks gene products for annotation. Biocurators
      select the top-ranked gene and mark annotation for these genes as 'in progress'
      or 'completed'; links enable biocurators to move directly to our biocuration
      interface (BI). Our BI includes all current GO annotation for gene products and
      is the main interface to add/modify AgBase curation data. The BI also displays
      Extracting Genic Information from Text (eGIFT) results for each gene product.
      eGIFT is a web-based, text-mining tool that associates ranked, informative terms
      (iTerms) and the articles and sentences containing them, with genes. Moreover,
      iTerms are linked to GO terms, where they match either a GO term name or a
      synonym. This enables AgBase biocurators to rapidly identify literature for
      further curation based on possible GO terms. Because most agricultural species do
      not have standardized literature, eGIFT searches all gene names and synonyms to
      associate articles with genes. As many of the gene names can be ambiguous, eGIFT
      applies a disambiguation step to remove matches that do not correspond to this
      gene, and filtering is applied to remove abstracts that mention a gene in
      passing. The BI is linked to our Journal Database (JDB) where corresponding
      journal citations are stored. Just as importantly, biocurators also add to the
      JDB citations that have no GO annotation. The AgBase BI also supports bulk
      annotation upload to facilitate our Inferred from electronic annotation of
      agricultural gene products. All annotations must pass standard GO Consortium
      quality checking before release in AgBase. Database URL:
      http://www.agbase.msstate.edu/.

PMID- 23160410
TI  - Steroid-induced microRNA let-7 acts as a spatio-temporal code for neuronal cell
      fate in the developing Drosophila brain.
AB  - Mammalian neuronal stem cells produce multiple neuron types in the course of an
      individual's development. Similarly, neuronal progenitors in the Drosophila brain
      generate different types of closely related neurons that are born at specific
      time points during development. We found that in the post-embryonic Drosophila
      brain, steroid hormones act as temporal cues that specify the cell fate of
      mushroom body (MB) neuroblast progeny. Chronological regulation of neurogenesis
      is subsequently mediated by the microRNA (miRNA) let-7, absence of which causes
      learning impairment due to morphological MB defects. The miRNA let-7 is required
      to regulate the timing of alpha'/beta' to alpha/beta neuronal identity transition
      by targeting the transcription factor Abrupt. At a cellular level, the ecdysone
      let-7-Ab signalling pathway controls the expression levels of the cell adhesion
      molecule Fasciclin II in developing neurons that ultimately influences their
      differentiation. Our data propose a novel role for miRNAs as transducers between
      chronologically regulated developmental signalling and physical cell adhesion.

PMID- 23160412
TI  - Opportunities for text mining in the FlyBase genetic literature curation
      workflow.
AB  - FlyBase is the model organism database for Drosophila genetic and genomic
      information. Over the last 20 years, FlyBase has had to adapt and change to keep
      abreast of advances in biology and database design. We are continually looking
      for ways to improve curation efficiency and efficacy. Genetic literature curation
      focuses on the extraction of genetic entities (e.g. genes, mutant alleles,
      transgenic constructs) and their associated phenotypes and Gene Ontology terms
      from the published literature. Over 2000 Drosophila research articles are now
      published every year. These articles are becoming ever more data-rich and there
      is a growing need for text mining to shoulder some of the burden of paper triage
      and data extraction. In this article, we describe our curation workflow, along
      with some of the problems and bottlenecks therein, and highlight the
      opportunities for text mining. We do so in the hope of encouraging the
      BioCreative community to help us to develop effective methods to mine this
      torrent of information. DATABASE URL: http://flybase.org

PMID- 23160413
TI  - Text mining in the biocuration workflow: applications for literature curation at
      WormBase, dictyBase and TAIR.
AB  - WormBase, dictyBase and The Arabidopsis Information Resource (TAIR) are model
      organism databases containing information about Caenorhabditis elegans and other
      nematodes, the social amoeba Dictyostelium discoideum and related Dictyostelids
      and the flowering plant Arabidopsis thaliana, respectively. Each database curates
      multiple data types from the primary research literature. In this article, we
      describe the curation workflow at WormBase, with particular emphasis on our use
      of text-mining tools (BioCreative 2012, Workshop Track II). We then describe the
      application of a specific component of that workflow, Textpresso for Cellular
      Component Curation (CCC), to Gene Ontology (GO) curation at dictyBase and TAIR
      (BioCreative 2012, Workshop Track III). We find that, with organism-specific
      modifications, Textpresso can be used by dictyBase and TAIR to annotate gene
      productions to GO's Cellular Component (CC) ontology.

PMID- 23160414
TI  - Accelerating literature curation with text-mining tools: a case study of using
      PubTator to curate genes in PubMed abstracts.
AB  - Today's biomedical research has become heavily dependent on access to the
      biological knowledge encoded in expert curated biological databases. As the
      volume of biological literature grows rapidly, it becomes increasingly difficult
      for biocurators to keep up with the literature because manual curation is an
      expensive and time-consuming endeavour. Past research has suggested that computer
      assisted curation can improve efficiency, but few text-mining systems have been
      formally evaluated in this regard. Through participation in the interactive text
      mining track of the BioCreative 2012 workshop, we developed PubTator, a PubMed
      like system that assists with two specific human curation tasks: document triage
      and bioconcept annotation. On the basis of evaluation results from two external
      user groups, we find that the accuracy of PubTator-assisted curation is
      comparable with that of manual curation and that PubTator can significantly
      increase human curatorial speed. These encouraging findings warrant further
      investigation with a larger number of publications to be annotated. Database URL:
      http://www.ncbi.nlm.nih.gov/CBBresearch/Lu/Demo/PubTator/

PMID- 23160415
TI  - Prioritizing PubMed articles for the Comparative Toxicogenomic Database utilizing
      semantic information.
AB  - The Comparative Toxicogenomics Database (CTD) contains manually curated
      literature that describes chemical-gene interactions, chemical-disease
      relationships and gene-disease relationships. Finding articles containing this
      information is the first and an important step to assist manual curation
      efficiency. However, the complex nature of named entities and their relationships
      make it challenging to choose relevant articles. In this article, we introduce a
      machine learning framework for prioritizing CTD-relevant articles based on our
      prior system for the protein-protein interaction article classification task in
      BioCreative III. To address new challenges in the CTD task, we explore a new
      entity identification method for genes, chemicals and diseases. In addition,
      latent topics are analyzed and used as a feature type to overcome the small size
      of the training set. Applied to the BioCreative 2012 Triage dataset, our method
      achieved 0.8030 mean average precision (MAP) in the official runs, resulting in
      the top MAP system among participants. Integrated with PubTator, a Web interface
      for annotating biomedical literature, the proposed system also received a
      positive review from the CTD curation team.

PMID- 23160416
TI  - Biocuration workflows and text mining: overview of the BioCreative 2012 Workshop
      Track II.
AB  - Manual curation of data from the biomedical literature is a rate-limiting factor
      for many expert curated databases. Despite the continuing advances in biomedical
      text mining and the pressing needs of biocurators for better tools, few existing
      text-mining tools have been successfully integrated into production literature
      curation systems such as those used by the expert curated databases. To close
      this gap and better understand all aspects of literature curation, we invited
      submissions of written descriptions of curation workflows from expert curated
      databases for the BioCreative 2012 Workshop Track II. We received seven qualified
      contributions, primarily from model organism databases. Based on these
      descriptions, we identified commonalities and differences across the workflows,
      the common ontologies and controlled vocabularies used and the current and
      desired uses of text mining for biocuration. Compared to a survey done in 2009,
      our 2012 results show that many more databases are now using text mining in parts
      of their curation workflows. In addition, the workshop participants identified
      text-mining aids for finding gene names and symbols (gene indexing),
      prioritization of documents for curation (document triage) and ontology concept
      assignment as those most desired by the biocurators. DATABASE URL:
      http://www.biocreative.org/tasks/bc-workshop-2012/workflow/.

PMID- 23160417
TI  - Peptide B12: emerging trends at the interface of inorganic chemistry, chemical
      biology and medicine.
AB  - The sophisticated and efficient delivery of vitamin B(12) ("B(12)") into cells
      offers promise for B(12)-bioconjugates in medicinal diagnosis and therapy. It is
      therefore surprising that rather little attention is presently paid to an
      alternative strategy in drug design: the development of structurally perfect, but
      catalytically inactive semi-artificial B(12) surrogates. Vitamin B(12) cofactors
      catalyse important biological transformations and are indispensible for humans
      and most other forms of life. This strong metabolic dependency exhibits enormous
      medicinal opportunities. Inhibitors of B(12) dependent enzymes are potential
      suppressors of fast proliferating cancer cells. This perspective article focuses
      on the design and study of backbone modified B(12) derivatives, particularly on
      peptide B(12) derivatives. Peptide B(12) is a recently introduced class of
      biomimetic cobalamins bearing an artificial peptide backbone with adjustable
      coordination and redox-properties. Pioneering biological studies demonstrated
      reduced catalytic activity, combined with inhibitory potential that is
      encouraging for future efforts in turning natural cofactors into new anti
      proliferative agents.

PMID- 23160418
TI  - Computational design of valence tautomeric adducts of Co(II) diketonates with
      redox-active o-benzoquinone ligands.
AB  - A new concept for the structural design of valence tautomeric (VT) metal
      complexes involving the formation of stable adducts of a tetracoordinate
      transition metal complex with a suitable bidentate redox-active ligand has been
      computationally studied using the DFT B3LYP*/6-311++G(d,p) method. The
      calculations, performed on a series of adducts of Co(II) diketonates with o
      benzoquinone and its mono- and diimines, showed that the mixed-ligand complexes
      of bis-(hexafluoroacetylacetonate) Co(II) with o-benzoquinone, o-benzoquinone
      imine and o-benzoquinone diimine satisfy the whole set of necessary conditions to
      be met by compounds exhibiting VT behaviour (stability of the adduct with respect
      to dissociation into the components, energy preference of the low-spin electronic
      state and thermally achievable energy barrier to intramolecular electron transfer
      determining the intrinsic mechanism of VT rearrangements). These compounds can be
      regarded as a feasible synthetic target of a broad series of mixed-ligand VT
      complexes.

PMID- 23160419
TI  - Nitrogen dioxide at the air-water interface: trapping, absorption, and solvation
      in the bulk and at the surface.
AB  - The interaction of NO(2) with water surfaces in the troposphere is of major
      interest in atmospheric chemistry. We examined an initial step in this process,
      the uptake of NO(2) by water through the use of molecular dynamics simulations.
      An NO(2)-H(2)O intermolecular potential was obtained by fitting to high-level ab
      initio calculations. We determined the binding of NO(2)-H(2)O to be about two
      times stronger than that previously calculated. From scattering simulations of an
      NO(2) molecule interacting with a water slab we observed that the majority of the
      scattering events resulted in outcomes in which the NO(2) molecule became trapped
      at the surface or in the interior of the water slab. Typical surface
      trapped/adsorbed and bulk-solvated/absorbed trajectories were analyzed to obtain
      radial distribution functions and the orientational propensity of NO(2) with
      respect to the water surface. We observed an affinity of the nitrogen atom for
      the oxygen in water, rather than hydrogen-bonding which was rare. The water
      solvation shell was less tight for the bulk-absorbed NO(2) than for the surface
      adsorbed NO(2). Adsorbed NO(2) demonstrated a marked orientational preference,
      with the oxygens pointing into the vacuum. Such behavior is expected for a mildly
      hydrophobic and surfactant molecule like NO(2). Estimates based on our results
      suggest that at high NO(2) concentrations encountered, for example, in some
      sampling systems, adsorption and reaction of NO(2) at the surface may contribute
      to the formation of gas-phase HONO.

PMID- 23160420
TI  - Branching geometry induced by lung self-regulated growth.
AB  - Branching morphogenesis is a widely spread phenomenon in nature. In
      organogenesis, it results from the inhomogeneous growth of the epithelial sheet,
      leading to its repeated branching into surrounding mesoderm. Lung morphogenesis
      is an emblematic example of tree-like organogenesis common to most mammals. The
      core signalling network is well identified, notably the Fgf10/Shh couple,
      required to initiate and maintain branching. In a previous study, we showed that
      the restriction by SHH of Fgf10 expression domain to distal mesenchyme
      spontaneously induces differential epithelial proliferation leading to branching.
      A simple Laplacian model qualitatively reproduced FGF10 dynamics in the
      mesenchyme and the spontaneous self-avoiding branching morphogenesis. However,
      early lung geometry has several striking features that remain to be addressed. In
      this paper, we investigate, through simulations and data analysis, if the FGF10
      diffusion scenario accounts for the following aspects of lung morphology: size
      dispersion, asymmetry of branching events, and distal epithelium-mesothelium
      equilibrium. We report that they emerge spontaneously in the model, and that most
      of the underlying mechanisms can be understood as dynamical interactions between
      gradients and shape. This suggests that specific regulation may not be required
      for the emergence of these striking geometrical features.

PMID- 23160422
TI  - Where, when, and in what form does sporadic Alzheimer's disease begin?
AB  - PURPOSE OF REVIEW: Intraneuronal lesions consisting of abnormal tau protein are
      seen to develop from the beginning until the end-phase of the pathological
      process underlying Alzheimer's disease. This review highlights the earliest phase
      of this process. RECENT FINDINGS: Development of abnormal tau frequently begins
      during childhood or puberty in nuclei of the lower brainstem sending diffuse
      projections to the cerebral cortex. Nonfibrillar abnormal tau material first
      occurs in the proximal axon of projection neurons in the locus coeruleus.
      Subsequently, a similar material (pretangle material) fills the somatodendritic
      compartment. In contrast with the pretangle material in cell bodies and
      dendrites, the nonfibrillar material in the axon normally does not convert into
      stable fibrillary inclusions. SUMMARY: Projection neurons (not only those of the
      locus coeruleus) are sturdy and can survive for a lifetime despite the existence
      of Alzheimer-related abnormal tau. Currently, little understood mechanisms most
      probably exist that enable neurons to fulfill their general functions even when
      severe tau pathology is present. The proclivity of predisposed neuronal types to
      develop abnormal tau may be intrinsic to the human brain. However, the tempo of
      disease progression reveals considerable individual differences, thereby offering
      opportunities to study conditions that may modify disease progression.

PMID- 23160423
TI  - Enhancing clinical trials in neurodegenerative disorders:  lessons from
      amyotrophic lateral sclerosis.
AB  - PURPOSE OF REVIEW: This review article is focused on strategies that may enhance
      clinical trial efficiency in neurodegenerative disorders, as demonstrated within
      the research field of amyotrophic lateral sclerosis (ALS). RECENT FINDINGS:
      Unravelling ALS pathophysiology will result in an increased number of candidate
      therapeutics. Recent ALS clinical trials have employed novel study designs that
      expedite the drug development process and limit sample size, including futility,
      lead-in, selection, adaptive and sequential designs. The search for sensitive and
      specific biomarkers in ALS continues to develop, and they are essential in
      accelerating the drug discovery process. Several candidate cerebrospinal fluid
      (CSF), neuroimaging and electrophysiological biomarkers have been recently
      described in ALS, and some have been successfully employed as secondary outcome
      measures in clinical trials. The advent of web-based technologies has provided a
      complementary platform to expedite clinical trials, through electronic data
      capture, teleconferencing and online registries. In addition, the formation of
      ALS consortia has enhanced collaborative multicentre studies. SUMMARY: ALS
      research studies have employed novel strategies to accelerate the efficiency and
      pace of drug discovery. The importance of adapting to novel measures that enhance
      study efficiency is not unique to ALS and can be applied to other
      neurodegenerative diseases in search of effective treatments.

PMID- 23160421
TI  - How do C9ORF72 repeat expansions cause amyotrophic lateral sclerosis and
      frontotemporal dementia:  can we learn from other noncoding repeat expansion
      disorders?
AB  - PURPOSE OF REVIEW: The aim of this review is to describe disease mechanisms by
      which chromosome 9 open reading frame 72 (C9ORF72) repeat expansions could lead
      to amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) and to
      discuss these diseases in relation to other noncoding repeat expansion disorders.
      RECENT FINDINGS: ALS and FTD are complex neurodegenerative disorders with a
      considerable clinical and pathological overlap, and this overlap is further
      substantiated by the recent discovery of C9ORF72 repeat expansions. These repeat
      expansions are currently the most important genetic cause of familial ALS and
      FTD, accounting for approximately 34.2 and 25.9% of the cases. Clinical
      phenotypes associated with these repeat expansions are highly variable, and
      combinations with mutations in other ALS-associated and/or FTD-associated genes
      may contribute to this pleiotropy. It is challenging, however, to diagnose
      patients with C9ORF72 expansions, not only because of large repeat sizes, but
      also due to somatic heterogeneity. Most other noncoding repeat expansion
      disorders share an RNA gain-of-function disease mechanism, a mechanism that could
      underlie the development of ALS and/or FTD as well. SUMMARY: The discovery of
      C9ORF72 repeat expansions provides novel insights into the pathogenesis of ALS
      and FTD and highlights the importance of noncoding repeat expansions and RNA
      toxicity in neurodegenerative diseases.

PMID- 23160425
TI  - Molecular predictors of outcome in low-grade glioma.
AB  - PURPOSE OF REVIEW: Recent and ongoing translational studies in neurooncology have
      investigated the role of molecular markers as potential predictors of outcome in
      patients with WHO grade I and II gliomas, commonly summarized as low-grade
      gliomas (LGGs). Here, we seek to highlight the most relevant molecular
      aberrations associated with these tumour types and update on recent findings on
      their potential prognostic and predictive value. RECENT FINDINGS: So far, no
      biomarker discussed has any relevance for the postoperative course of disease
      without genotoxic treatment. Isocitrate dehydrogenase (IDH) mutations, 1p
      deletion or 1p/19q codeletion have the strongest prognostic impact on survival of
      patients with LGG, given a genotoxic treatment is provided. Recent findings from
      phase III clinical trials on anaplastic oligodendroglial tumours conducted in
      North America and Europe suggest that the addition of procarbazine, lomustine and
      vincristine to radiotherapy is beneficial in the treatment of anaplastic gliomas
      with 1p/19q codeletion. To decipher the role of 1p/19q codeletion in LGG will be
      challenging. Recent developments in v-raf murine sarcoma viral oncogene homolog
      B1 (BRAF)(V600E)-specific small molecule inhibitors and their clinical approval
      for other cancer types could turn BRAF(V600E) into a promising molecular
      predictor of outcome in pilocytic astrocytomas, given a treatment with a mutation
      specific BRAF inhibitor is applied. SUMMARY: Clinical prognostic factors such as
      age, tumour size and the presence or absence of clinical symptoms have long been
      recognized in the management of patients with LGGs. Molecular biomarkers are
      increasingly evolving as additional factors that facilitate diagnostics and
      therapeutic decision-making. However, further prospective randomized studies
      including multivariate analyses are needed to clearly distinguish between
      prognostic and predictive effects.

PMID- 23160424
TI  - Emerging operative strategies in neurosurgical oncology.
AB  - PURPOSE OF REVIEW: In recent years, the safety and efficacy of neurosurgical
      intervention has rapidly improved for brain tumor patients. Technological
      advances, combined with refined intraoperative techniques, now enable well
      tolerated surgical access to any region of the human brain. For patients with
      gliomas, these improvements have redefined the clinical possibilities, and here
      we review several emerging operative strategies that are essential for next
      generation neurosurgical oncologists and major brain tumor centers. RECENT
      FINDINGS: The value of glioma extent of resection remains controversial, but
      review of the modern literature reveals important opportunities for early
      neurosurgical intervention. Although microsurgical resection must be balanced by
      the risk of neurological compromise, improvements in intraoperative stimulation
      techniques now enable resection of highly eloquent tumors with minimal morbidity.
      Additionally, the emergence of fluorescence-guided surgery as a new operative
      paradigm provides a unique opportunity to resect tumors to the margins of
      microscopic infiltration. SUMMARY: Neurosurgical intervention remains the first
      step in effective glioma management. With intraoperative mapping techniques,
      aggressive microsurgical resection can be safely pursued even when tumors occupy
      essential functional pathways. With the development of tumor-specific
      fluorophores, such as 5-aminolevulinic acid, real-time microscopic visualization
      of tumor infiltration can be surgically targeted prior to adjuvant therapy.

PMID- 23160426
TI  - Current world literature.

PMID- 23160430
TI  - Does stent implantation improve the result of repeat embolization in recanalized
      aneurysms?
AB  - BACKGROUND: Although endovascular technique and related devices continue to
      improve, recanalization of embolized aneurysm remains a pitfall of this approach.
      The problem of how to treat the recanalized aneurysm needs to be addressed.
      OBJECTIVE: To determine the outcomes of patients undergoing repeat embolization
      for recanalized intracranial aneurysms and to evaluate the impact of stent
      implantation on subsequent recanalization. METHODS: Between September 2001 and
      September 2011, we performed endovascular retreatment in 162 patients with a
      total of 197 recanalized intracranial aneurysms. Stent implantation was performed
      in 68 aneurysms during the retreatment. Clinical and morphological outcomes were
      assessed at 6 months or more after repeat embolization. RESULTS: Procedure
      related complications, including asymptomatic thromboembolism, occurred with 15
      aneurysms (7.6%) without permanent neurological sequelae. Follow-up imaging of
      172 aneurysms documented stable occlusion in 96 of the lesions (55.8%), minor
      recanalization in 17 (9.9%), and major recanalization in 59 (34.3%) during the
      mean follow-up period of 26.0 +/- 18.0 months. In multiple logistic regression
      analysis, stent implantation was shown to reduce the major recanalization rate at
      6 months after retreatment (odds ratio: 0.161; 95% confidence interval:, 0.038
      0.670; P = .012) and thereafter (odds ratio: 0.226; 95% confidence interval:
      0.088-0.581; P = .002). CONCLUSION: Stent implantation, as well as compact coil
      packing, at the time of repeat embolization seems beneficial in reducing rates of
      further recanalization.

PMID- 23160431
TI  - Formaldehyde carcinogenicity research: 30 years and counting for mode of action,
      epidemiology, and cancer risk assessment.
AB  - Formaldehyde is a widely used high production chemical that is also released as a
      byproduct of combustion, off-gassing of various building products, and as a
      fixative for pathologists and embalmers. What is not often realized is that
      formaldehyde is also produced as a normal physiologic chemical in all living
      cells. In 1980, chronic inhalation of high concentrations of formaldehyde was
      shown to be carcinogenic, inducing a high incidence of nasal squamous cell
      carcinomas in rats. Some epidemiologic studies have also found increased numbers
      of nasopharyngeal carcinoma and leukemia in humans exposed to formaldehyde that
      resulted in formaldehyde being considered a Known Human Carcinogen. This article
      reviews the data for rodent and human carcinogenicity, early Mode of Action
      studies, more recent molecular studies of both endogenous and exogenous DNA
      adducts, and epigenetic studies. It goes on to demonstrate the power of these
      research studies to provide critical data to improve our ability to develop
      science-based cancer risk assessments, instead of default approaches. The
      complexity of constant physiologic exposure to a known carcinogen requires that
      new ways of thinking be incorporated into determinations of cancer risk
      assessment for formaldehyde, other endogenous carcinogens, and the role of
      background endogenous DNA damage and mutagenesis.

PMID- 23160432
TI  - Which exercises target the gluteal muscles while minimizing activation of the
      tensor fascia lata? Electromyographic assessment using fine-wire electrodes.
AB  - STUDY DESIGN: Controlled laboratory study, repeated-measures design. OBJECTIVES:
      To compare hip abductor muscle activity during selected exercises using fine-wire
      electromyography, and to determine which exercises are best for activating the
      gluteus medius and the superior portion of the gluteus maximus, while minimizing
      activity of the tensor fascia lata (TFL). BACKGROUND: Abnormal hip kinematics
      (ie, excessive hip adduction and internal rotation) has been linked to certain
      musculoskeletal disorders. The TFL is a hip abductor, but it also internally
      rotates the hip. As such, it may be important to select exercises that activate
      the gluteal hip abductors while minimizing activation of the TFL. METHODS: Twenty
      healthy persons participated. Electromyographic signals were obtained from the
      gluteus medius, superior gluteus maximus, and TFL muscles using fine-wire
      electrodes as subjects performed 11 different exercises. Normalized
      electromyographic signal amplitude was compared among muscles for each exercise,
      using multiple 1-way repeated-measures analyses of variance. A descriptive
      gluteal-to-TFL muscle activation index was used to identify preferred exercises
      for recruiting the gluteal muscles while minimizing TFL activity. RESULTS: Both
      gluteal muscles were significantly (P<.05) more active than the TFL in unilateral
      and bilateral bridging, quadruped hip extension (knee flexed and extending), the
      clam, sidestepping, and squatting. The gluteal-to-TFL muscle activation index
      ranged from 18 to 115 and was highest for the clam (115), sidestep (64),
      unilateral bridge (59), and both quadruped exercises (50). CONCLUSION: If the
      goal of rehabilitation is to preferentially activate the gluteal muscles while
      minimizing TFL activation, then the clam, sidestep, unilateral bridge, and both
      quadruped hip extension exercises would appear to be the most appropriate.

PMID- 23160434
TI  - M1.3--a small scaffold for DNA origami .
AB  - The DNA origami method produces programmable nanoscale objects that form when one
      long scaffold strand hybridizes to numerous oligonucleotide staple strands. One
      scaffold strand is dominating the field: M13mp18, a bacteriophage-derived vector
      7249 nucleotides in length. The full-length M13 is typically folded by using over
      200 staple oligonucleotides. Here we report the convenient preparation of a 704
      nt fragment dubbed "M1.3" as a linear or cyclic scaffold and the assembly of
      small origami structures with just 15-24 staple strands. A typical M1.3 origami
      is large enough to be visualized by TEM, but small enough to show a cooperativity
      in its assembly and thermal denaturation that is reminiscent of oligonucleotide
      duplexes. Due to its medium size, M1.3 origami with globally modified staples is
      affordable. As a proof of principle, two origami structures with globally 5'
      capped staples were prepared and were shown to give higher UV-melting points than
      the corresponding assembly with unmodified DNA. M1.3 has the size of a gene, not
      a genome, and may function as a model for gene-based nanostructures. Small
      origami with M1.3 as a scaffold may serve as a workbench for chemical, physical,
      and biological experiments.

PMID- 23160436
TI  - Crystal structure and functional studies of an unusual L-cysteine desulfurase
      from Archaeoglobus fulgidus.
AB  - L-Cysteine desulfurase IscS and scaffold IscU proteins are universally involved
      in Fe/S cluster synthesis. The Archaeoglobus fulgidus (Af) genome encodes
      proteins having a high degree of primary structure similarity to IscS and IscU
      from other organisms. However, AfIscS is unusual because it lacks the active site
      lysine residue that normally forms an internal Schiff base with pyridoxal
      phosphate (PLP) and serves as a base during catalysis. Our as-isolated
      recombinant AfIscS contains pyridoxamine phosphate (PMP) instead of the expected
      PLP and lacks desulfurase activity. We have solved its structure to 1.43 A
      resolution and found that PMP binds non-covalently at the PLP site of the enzyme
      and displays significant disorder. However, the previously reported structure of
      recombinant Af(IscU-D35A-IscS)(2) contains an in vivo generated [Fe(2)S(2)]
      species within AfIscU and the question arises as to how its sulfides were
      generated. Here, we report that adding PLP to AfIscS produces an enzyme that
      displays in vitro L-cysteine desulfurase activity mediating the synthesis of a
      stable holo Af(IscU-D35A-IscS) complex.

PMID- 23160437
TI  - Anti-stiffness effect of apocynin in deoxycorticosterone acetate-salt
      hypertensive rats via inhibition of oxidative stress.
AB  - This study sought to determine if apocynin, a nicotinamide adenine dinucleotide
      phosphate oxidase inhibitor, would attenuate arterial stiffness in salt-sensitive
      hypertensive rats via structural and functional changes in conduit arteries. We
      showed that tail blood pressure was significantly higher in deoxycorticosterone
      acetate-salt-induced hypertensive (DSH) rats compared with the sham control group
      (P<0.01). Morphological analysis and biochemical assay showed that large arteries
      in DSH rats underwent significant remodeling including increased medial thickness
      in carotid arteries compared with the control rats (194.25+/-5.66 vs. 120.48+/
      7.93 MUm, P<0.05) and increased collagen deposition in thoracic aorta (1.03+/
      0.09 vs. 0.85+/-0.04 mg cm(-1), P<0.05). These changes were associated with
      increases in reactive oxygen species (ROS) level and increased thoracic aortic
      stiffness compared with the control rats (6.21+/-0.79 m s(-1) vs. 4.64+/-0.59 m
      s(-1), P<0.01). Treatment with apocynin significantly prevented ROS increases and
      collagen deposition (0.84+/-0.04 vs. 1.03+/-0.09 mg cm(-1), P<0.05), and reduced
      arterial stiffness as shown by decreased pulse wave velocity in the thoracic
      aorta (5.31+/-0.88 vs. 6.21+/-0.79 m s(-1), P<0.01). Additionally, apocynin
      prevented carotid artery wall thickening (58.57+/-3.40 vs. 78.89+/-4.10 MUm,
      P<0.05). In conclusion we have shown that increased ROS level is associated with
      increased aortic stiffness, and deposition of collagen in the aortic arterial
      wall in DSH rats. Apocynin prevented ROS increases and arterial stiffness in DSH
      rats. Antioxidant therapy may be a potential treatment of large arterial
      stiffness in salt-sensitive hypertension.

PMID- 23160438
TI  - Compression of perceived depth as a function of viewing conditions.
AB  - PURPOSE: The magnification produced by a low-vision telescope has been shown to
      compress perceived depth. Looking through such a telescope, however, also entails
      monocular viewing and visual field restriction, and these viewing conditions,
      taken together, were also shown to compress perceived depth. The research
      presented here quantitatively explores the separate effects of each of these
      viewing conditions on perceived depth. METHODS: Participants made verbal
      estimates of the length, relative to the width, of rectangles presented in a
      controlled table-top setting. In experiment 1, the rectangles were either in the
      frontal plane or receding in depth, and they were viewed either binocularly or
      monocularly with an unrestricted field of view (FOV). In experiment 2, the
      rectangles were in depth and were viewed monocularly with an unrestricted FOV, a
      moderately (40 degrees) restricted FOV, or a severely (11.5 degrees) restricted
      FOV. RESULTS: Viewed in the frontal plane, either monocularly or binocularly, the
      vertical dimension was expanded by about 10%. Viewed in depth, with an
      unrestricted FOV, the (projectively vertical) depth dimension was compressed by
      12% when seen binocularly or 24% when seen monocularly. A monocular moderately
      (40 degrees) restricted FOV was very similar to the unrestricted monocular FOV. A
      severely (11.5 degrees) restricted FOV, however, produced a substantially greater
      44% compression of perceived depth. CONCLUSIONS: Even under near-optimal
      binocular viewing conditions, there is some compression of perceived depth. The
      compression found when viewing through a low-vision telescope has been shown to
      be substantially greater. In addition to the previously demonstrated contribution
      of telescopic magnification to this effect, we have now shown that the viewing
      conditions of monocularity and severely restricted (11.5 degrees) FOV can each
      produce substantial increments in the compression of perceived depth. We found,
      however, that a moderately restricted (40 degrees) FOV does not increase the
      compression found with unrestricted monocular viewing.

PMID- 23160440
TI  - The effect of cycloplegia on the lenstar and the IOLMaster biometry.
AB  - PURPOSE: To evaluate the effect of cycloplegia on ocular biometry measurements
      and intraocular lens (IOL) power calculation using the Lenstar LS900 (Haag-Streit
      AG, Koeniz, Switzerland) and the IOLMaster (Carl Zeiss Meditec AG, Jena, Germany)
      biometers and to assess the agreement between the devices. METHODS: Measurements
      were taken with the Lenstar and the IOLMaster on 43 healthy volunteers with a
      mean age of 22.1 +/- 4.7 years (range, 18 to 37 years). Axial length (AL),
      anterior chamber depth (ACD), corneal curvature, and horizontal iris width (white
      to-white [WTW]) measurements were performed with and without cycloplegia. The IOL
      powers were calculated using four formulas: Sanders-Retzlaff-Kraff/Theoretical,
      Holladay 1, Hoffer Q, and Haigis. RESULTS: Cycloplegia had no significant effect
      on AL or corneal curvature. However, ACD and WTW significantly increased
      postcycloplegia (Lenstar, 0.09 +/- 0.06 mm and 0.10 +/- 0.17 mm, respectively;
      IOLMaster, 0.06 +/- 0.07 mm and 0.43 +/- 0.35 mm, respectively; p <0.001). The
      Lenstar AL measurements were statistically but not clinically significantly
      longer than those of the IOLMaster (precycloplegia, 0.03 +/- 0.03 mm;
      postcycloplegia, 0.02 +/- 0.03 mm; p < 0.001). For ACD measurements, the 95%
      limits of agreement were -0.19 to 0.20 mm without cycloplegia and -0.11 to 0.17
      mm with cycloplegia. The 95% limits of agreement for WTW measurements were -1.07
      to 0.45 mm with cycloplegia. The only significantly different IOL power
      precycloplegia and postcycloplegia was with the Haigis formula and the Lenstar
      measurements: 15.12 +/- 3.87 diopters and 15.26 +/- 3.92 diopters (p < 0.01).
      CONCLUSIONS: Cycloplegia affected ACD and WTW but not AL or corneal curvature
      measurements. Generally, good agreement was found between the Lenstar and the
      IOLMaster, although not for WTW. Differences between these devices do not produce
      a clinically significant impact on IOL power.

PMID- 23160439
TI  - Perceived suprathreshold depth under conditions that elevate the stereothreshold.
AB  - PURPOSE: Previous studies considered the possibility that individuals with
      impaired stereoacuity can be identified by estimating the perceived depth of a
      target with a suprathreshold retinal image disparity. These studies showed that
      perceived suprathreshold depth is reduced when the image presented to one eye is
      blurred, but they did not address whether a similar reduction of perceived depth
      occurs when the stereothreshold is elevated using other manipulations. METHODS:
      Stereothresholds were measured in six adult observers for a pair of bright 1
      degree vertical lines during normal viewing and under five conditions that
      elevated the stereothreshold: monocular dioptric blur, monocular glare, binocular
      luminance reduction, monocular luminance reduction, and imposed disjunctive image
      motion. The observers subsequently matched the perceived depth of degraded
      targets presented with crossed or uncrossed disparities corresponding to two,
      four, and six times the elevated stereothreshold for each stimulus condition.
      RESULTS: The image manipulations used elevated the stereothreshold by a factor of
      3.7 to 5.5 times. For targets with suprathreshold disparities, monocular blur,
      monocular luminance reduction, and disjunctive image motion resulted in a
      significant decrease in perceived depth. However, the magnitude of perceived
      suprathreshold depth was unaffected when monocular glare was introduced or the
      binocular luminance of the stereotargets was reduced. CONCLUSIONS: Not all
      conditions that increase the stereothreshold reduce the perceived depth of
      targets with suprathreshold disparities. Observers who have poor stereopsis
      therefore may or may not exhibit an associated reduction of perceived
      suprathreshold depth.

PMID- 23160441
TI  - The effect of daily lens replacement during overnight wear on ocular adverse
      events.
AB  - PURPOSE: Compared with daily disposable wear schedule, continuous wear (CW) or
      extended wear of contact lenses has been associated with an increased risk of
      developing an ocular infection. Proof-of-principle studies were conducted to
      investigate the impact of daily replacement of lenses on the rate of contact lens
      related ocular adverse events (AEs) during 30-night CW. METHODS: A total of 215
      subjects were dispensed with silicone hydrogel lenses on a 30-night CW schedule
      but replaced lenses daily either each night before sleeping (n = 178 eyes) or
      each morning after waking (n = 252 eyes). Scheduled clinic visits were conducted
      at 1 week and 1 month. Neophytes were required to complete 1 week of daily wear
      before commencing CW. A historical control (n = 191 eyes) using the same site,
      subject demographics, and visit schedule but monthly lens replacement was used
      for AE rates. RESULTS: Logistic regression analysis showed a significant
      reduction in mechanical AEs (0.8 vs 5.2%, p = 0.01) and overall AEs (inflammatory
      and mechanical events) (4.0 vs 8.9%, p = 0.04) when lenses were replaced each
      morning compared with being replaced monthly. Estimation of handling-related lens
      contamination of unworn lenses in a subgroup of subjects showed isolation of
      Staphylococcus aureus from the lenses of 35% of subjects, and 65% of subjects had
      more than 1000 colony-forming units per lens of gram-positive bacterial
      contamination. CONCLUSIONS: Morning lens replacement during CW reduced mechanical
      and overall ocular AEs. Replacing lenses at night had no beneficial effects
      perhaps because the benefit of a fresh lens at night might be partially negated
      by contamination of the contact lens caused by lens handling before overnight eye
      closure. Contact lens wearers on an extended wear or CW schedule should be
      advised to minimize lens handling before sleep to reduce the risk of
      complications.

PMID- 23160442
TI  - Blood pressure, vessel caliber, and retinal thickness in diabetes.
AB  - PURPOSE: In this study, we examine the association of blood pressure (BP),
      retinal thickness (RT), and vessel caliber in patients with type 2 diabetes and
      high HbA1c (elevated long-term blood glucose) with or without mild or moderate
      nonproliferative diabetic retinopathy (NPDR). METHODS: Forty-three patients with
      type 2 diabetes and high HbA1c measures (23 without NPDR and 20 with mild to
      moderate NPDR) and 22 age-matched nondiabetic controls participated. The BP, RT
      (Stratus OCT3), fundus photography, and HbA1c were measured. Correlations between
      BP, HbA1c, vessel caliber, and RT were evaluated. RESULTS: Diastolic BP (DBP) is
      positively and significantly associated with RT in patients with NPDR (p < 0.02).
      Blood pressure was not associated with RT in patients without NPDR (p = 0.83).
      There is an association between higher HbA1c and higher DBP within the NPDR group
      (p < 0.02). Furthermore, HbA1c modifies the slope of the relationship between DBP
      and RT in NPDR patients. Greater venule diameters and loss of the correlation
      between decreased arteriole size and increased systolic blood pressure, seen in
      controls, were observed in patients with and without NPDR. CONCLUSIONS: The
      results of this study show that HbA1c and BP together have an impact on RT
      measures of patients with DR. These measures should be considered when evaluating
      RT in patients with DR both clinically and in future optical coherence tomography
      studies on this population.

PMID- 23160443
TI  - Optometrists' clinical reasoning made explicit:  a qualitative study.
AB  - PURPOSE: Because the clinical reasoning processes engaged in by practicing
      optometrists have not previous been investigated, until now, there has been no
      way of knowing whether models of clinical reasoning from other health professions
      can be transposed to optometry. The purpose of this study has therefore been
      twofold: making explicit the clinical reasoning processes of optometrists at both
      the "competent" and "expert" levels and comparing these processes to highlight
      the characteristics of clinical reasoning expertise. METHODS: Four competent
      level optometrists and four expert-level optometrists participated in this
      qualitative study. Each optometrist performed a complete optometric examination
      on a preselected patient. Each of these examinations was recorded on a DVD video
      and followed by a feedback session, also captured on a DVD video. The feedback
      session was conducted using techniques inspired by a form of interview called the
      "explicitation interview," aiming to describe optometrists' mental actions and
      the time sequence of these actions throughout the examination. RESULTS: The
      results indicate that optometrists' clinical reasoning is patient centered and
      includes both analytical and nonanalytical modes of reasoning. When compared with
      a competent-level optometrist, an expert-level optometrist is more patient
      centered, formulates an earlier mental representation of the patient's clinical
      situation (including diagnosis formulation), plans examinations more thoroughly,
      is able to analyze and reflect during cognitively demanding tasks, and draws up
      his or her care management plan throughout the entire examination. CONCLUSIONS:
      The verbalization of optometrists' clinical reasoning processes represents a
      first step toward a better understanding of this competency. The impact of this
      research on optometric education is discussed. The results open doors to further
      research in the field, for example, toward defining the stages of clinical
      reasoning development among optometry students and professionals.

PMID- 23160444
TI  - Nitric oxide and the A and B of endothelin of sodium homeostasis.
AB  - PURPOSE OF REVIEW: In recent years, renal collecting duct-specific endothelin-1
      (ET1), endothelin A (ETA) and endothelin B (ETB) receptors as well as nitric
      oxide synthase 1 (NOS1) knockout mice have been developed with subsequent
      identification for an integral role in regulation of sodium water homeostasis and
      ultimately blood pressure. The focus of this review is to integrate these models
      and to propose a scheme for the control of sodium excretion by the collecting
      duct and the endothelin/ETB/NOS system. RECENT FINDINGS: NOS1 splice variants are
      expressed in the kidney, especially in the collecting duct. Mice express
      predominantly NOS1beta in the medulla, with NOS1alpha and NOS1beta in the cortex,
      whereas rats express NOS1alpha and NOS1beta in both the cortex and medulla. Novel
      transcription of collecting duct ET1 mediated by epithelial sodium channels,
      mitochondrial Na/Ca exchangers and glucocorticoids has been determined. ET1 via
      the ETB receptor increases nitric oxide production in both rat and mouse
      collecting ducts, suggesting that NOS1beta is linked to ET1-dependent NOS
      activation in the kidney. As well, genetic deletion of NOS1 splice variants in
      the collecting duct results in a salt-sensitive hypertensive phenotype in mice,
      much like the collecting duct ET1 and collecting duct ETB knockout mice. SUMMARY:
      In the collecting duct, the ET1/nitric oxide pathways are intimately linked, and
      deletion of collecting duct ET1, ETB receptor or NOS1beta results in a salt
      sensitive phenotype, which is at least partially dependent on dysregulation of
      sodium and water reabsorption.

PMID- 23160448
TI  - Solvothermal synthesis and characterization of thioindate-thioantimonates with
      transition-metal complexes: the first examples of the incorporation of transition
      metal ions into In-S-Sb frameworks.
AB  - Three new thioindate-thioantimonates [Ni(en)(3)][In(2)Sb(2)S(7)] (1, en =
      ethylenediamine), [(Ni(en)(3))](3)(en)[In(6)Sb(6)S(21)] (2), and
      [Co(tren)InSbS(4)] (3, tren = tris(2-aminoethyl)amine) have been solvothermally
      synthesized and structurally characterized. Compound 1 contains dimeric
      [In(2)S(7)] units built of two tetrahedral [InS(4)] units sharing one corner and
      [SbS(3)] trigonal-pyramids, which are interconnected to form a puckered
      [In(2)Sb(2)S(7)](n)(2n-) layer with 4-, 5- and 6-heterorings. [Ni(en)(3)](2+)
      complex cations as structure-directing and charge-balancing agents are located at
      the interlayer spaces. Compound 2 consists of a 3-D polymeric
      [In(6)Sb(6)S(21)](n)(6n-) anion, [Ni(en)(3)](2+) cations, free en molecule and a
      water molecule. The 3-D polymeric [In(6)Sb(6)S(21)](n)(6n-) anion is composed of
      [In(2)Sb(2)S(8)](n)(4n-) chains and heterometallic [In(2)Sb(2)S(9)] clusters,
      which are interconnected to give 3-D frameworks with 10-ring helical channels, 14
      and 20-ring channels. Compound 3 contains dimeric [In(2)S(6)] units constructed
      by two tetrahedral [InS(4)] sharing a common edge and [SbS(3)] trigonal-pyramids,
      which link to form a new [InSbS(4)](n)(2n-) layer with large 10-heterorings. Each
      [Co(tren)](2+) group is appended within the cavity of the 10-heteroring via one
      Co-S-Sb bond. 3 represents the first example of the incorporation of transition
      metal ions into a In-S-Sb framework. Density functional theory calculation for 3
      also has been performed, and the optical properties of 1-3 have been
      characterized by UV-vis spectra.

PMID- 23160445
TI  - Regional differences in actomyosin contraction shape the primary vesicles in the
      embryonic chicken brain.
AB  - In the early embryo, the brain initially forms as a relatively straight,
      cylindrical epithelial tube composed of neural stem cells. The brain tube then
      divides into three primary vesicles (forebrain, midbrain, hindbrain), as well as
      a series of bulges (rhombomeres) in the hindbrain. The boundaries between these
      subdivisions have been well studied as regions of differential gene expression,
      but the morphogenetic mechanisms that generate these constrictions are not well
      understood. Here, we show that regional variations in actomyosin-based
      contractility play a major role in vesicle formation in the embryonic chicken
      brain. In particular, boundaries did not form in brains exposed to the nonmuscle
      myosin II inhibitor blebbistatin, whereas increasing contractile force using
      calyculin or ATP deepened boundaries considerably. Tissue staining showed that
      contraction likely occurs at the inner part of the wall, as F-actin and
      phosphorylated myosin are concentrated at the apical side. However, relatively
      little actin and myosin was found in rhombomere boundaries. To determine the
      specific physical mechanisms that drive vesicle formation, we developed a finite
      element model for the brain tube. Regional apical contraction was simulated in
      the model, with contractile anisotropy and strength estimated from contractile
      protein distributions and measurements of cell shapes. The model shows that a
      combination of circumferential contraction in the boundary regions and relatively
      isotropic contraction between boundaries can generate realistic morphologies for
      the primary vesicles. In contrast, rhombomere formation likely involves
      longitudinal contraction between boundaries. Further simulations suggest that
      these different mechanisms are dictated by regional differences in initial
      morphology and the need to withstand cerebrospinal fluid pressure. This study
      provides a new understanding of early brain morphogenesis.

PMID- 23160449
TI  - CBL-B is required for leukemogenesis mediated by BCR-ABL through negative
      regulation of bone marrow homing.
AB  - BCR-ABL induces chronic myeloid leukemia (CML) through the aberrant regulation of
      multiple signaling substrates. Previous research has shown that BCR-ABL mediates
      down-modulation of CBL-B protein levels. A murine bone marrow transplantation
      (BMT) study was performed to assess the contribution of Cbl-b to BCR-ABL-induced
      disease. The predominant phenotype in the Cbl-b(-/-) recipients was a CML-like
      myeloproliferative disease (MPD) similar to that observed in the wild-type
      animals, but with a longer latency, diminished circulating leukocyte numbers and
      reduced spleen weights. Despite the decreased leukemic burden in comparison to
      their wild-type counterparts, the Cbl-b(-/-) animals displayed enhanced numbers
      of Gr-1(+)/Mac-1(+) spleen cells and neutrophilia. On the basis of prior evidence
      of CBL-B-dependent motility toward SDF-1alpha, we hypothesized that Cbl-b
      deficiency might impair bone marrow localization during transplantation. Homing
      experiments showed reduced migration of Cbl-b(-/-) cells to the bone marrow.
      Intrafemoral transplantation of BCR-ABL-transduced Cbl-b(-/-) cells revealed
      equivalent latency of disease development to the wild-type transplants,
      supporting the conclusion that Cbl-b deficiency diminishes homing of leukemic
      cells to the bone marrow, and perturbs the proliferation of BCR-ABL-expressing
      malignant clones during CML development.

PMID- 23160450
TI  - PPAR-alpha is a therapeutic target for chronic lymphocytic leukemia.
AB  - Chronic lymphocytic leukemia (CLL) cells with aggressive clinical properties
      express lipoprotein lipase (LPL), which generates activating ligands for the
      nuclear receptor peroxisome proliferator activated receptor (PPAR)alpha and
      allows fatty acids to be used as fuel. However, the role of PPARalpha in CLL is
      unclear. PPARalpha was found to be expressed by circulating CLL cells and highly
      associated with advanced stage disease. Consistent with this observation,
      palmitate oxidation rates in circulating CLL cells were similar to more
      conventional fat-burning cells such as muscle. Transgenic expression of PPARalpha
      in CD5(+) Daudi cells increased both their expression of immunosuppressive
      factors (that is, interleukin (IL)10 and phospho-STAT3) and resistance to
      metabolic and cytotoxic stressors. In contrast, marked downregulation of
      PPARalpha expression accompanied immunogenic death of proliferating CLL cells.
      The PPARalpha antagonist MK886 killed circulating CLL cells directly, caused
      proliferating CLL cells to enter an immunogenic death pathway and cleared CLL
      xenografts from immunodeficient mice. These results suggest that PPARalpha is a
      biological mediator of CLL and MK886 is a clinically relevant agent with activity
      against CLL.

PMID- 23160451
TI  - Increasing organic solar cell efficiency with polymer interlayers.
AB  - We demonstrate how organic solar cell efficiency can be increased by introducing
      a pure polymer interlayer between the PEDOT:PSS layer and the polymer:fullerene
      blend. We observe an increase in device efficiency with three different material
      systems over a number of devices. Using both electrical characterization and
      numerical modeling we show that the increase in efficiency is caused by optical
      absorption in the pure polymer layer and hence efficient charge separation at the
      polymer bulkheterojunction interface.

PMID- 23160452
TI  - [Skin bacteria direct the immune response].

PMID- 23160453
TI  - Complex working memory span in cochlear implanted and normal hearing teenagers.

PMID- 23160454
TI  - Dizziness handicap after cartilage cap occlusion for superior semicircular canal
      dehiscence.
AB  - OBJECTIVE: To evaluate the change in self-reported dizziness handicap after
      surgical repair using the cartilage cap occlusion technique in cases of superior
      canal dehiscence (SCD). STUDY DESIGN: Repeated measures, retrospective chart
      review. SETTING: Tertiary referral center. PATIENTS: Twenty patients over a 2
      year period who underwent surgical repair of SCD using the cartilage cap
      occlusion technique. INTERVENTION: Therapeutic. MAIN OUTCOME MEASURE:
      Preoperative and postoperative Dizziness Handicap Inventory (DHI) questionnaires
      were completed (median, interquartile range). RESULTS: Preoperative (48, 28-56)
      and postoperative (33, 19-50) total scores were not significantly different.
      Scores for patients with moderate/severe preoperative DHI scores (DHI, >30; n =
      14) demonstrated significant change (p = 0.001, Wilcoxon paired sample test),
      whereas those with mild scores did not (DHI, <= 30; n = 6; p = 0.67). CONCLUSION:
      Change in DHI score is variable. As described by DHI score, patients with higher
      preoperative handicap may demonstrate significant improvement after surgery,
      whereas those with mild handicap may not. These results are similar to previous
      reports and indicate that the cartilage cap occlusion technique may provide an
      alternative to middle fossa craniotomy approach for surgical management of
      symptomatic SCD.

PMID- 23160455
TI  - Comparison between 2 laser systems, Er-Yag and CO2, in stapes surgery.
AB  - OBJECTIVE: The aim of the study was to compare 2 laser systems, Er-Yag and CO2,
      in stapes surgery. STUDY DESIGN: The study design was retrospective. SETTING: The
      study was conducted at an academic tertiary referral center. PATIENTS: There were
      88 women and 34 man in the analyzed group. The study was carried out on 142 ears:
      52 on the right ear, 50 on the left ear, and 20 bilateral. Forty-seven ears
      underwent a CO2 laser-assisted stapedotomy, and 95 underwent Er-Yag-assisted
      stapedotomy; 23 left and 24 right ears were operated on using the CO2 laser. The
      Er-Yag laser was used in 48 right and 47 left ears. The follow-up time was at
      least 1 year. RESULTS: When the postoperative air-bone gap was compared with the
      preoperative air-bone gap for the 2 laser systems using the Student t test, as
      well as the Mann-Whitney U test, no statistical differences were found between
      the 2 groups, that is, with the use of Er-Yag and CO2 lasers. Also, no
      statistically significant differences were measured over all frequencies by the
      Student t test between preoperative and postoperative bone conduction in each
      group. CONCLUSION: To sum up, our observations have proven the usefulness of 2
      laser systems: CO2 and Er-Yag lasers in stapes surgery. In both groups, a
      decrease in the hearing threshold was obtained.

PMID- 23160458
TI  - The management of HIV-infected pregnant women.
AB  - PURPOSE OF REVIEW: The purpose of this article is to update the current practice
      in the management of HIV-infected pregnant women and present evidence-based
      recommendations for the reduction of mother-to-child transmission. RECENT
      FINDINGS: Early and sustained control of HIV viral replication is associated with
      decreasing residual risk of transmission and favors initiating antiretroviral
      drugs sufficiently early in naive women to suppress viral replication by the
      third trimester; however, this potential benefit must be balanced against the
      unknown long-term outcome of first-trimester drug exposure. Efavirenz should
      whenever possible be avoided in the first trimester of gestation, but its use
      seems well tolerated for 39 days after last menstrual period when the neural tube
      closes. Raltegravir may be considered in special circumstances in pregnancy.
      SUMMARY: The HIV viral load and the risk factors for prematurity must be
      considered when deciding when to start antiretroviral treatment in each
      individual pregnant woman. A ritonavir-boosted protease inhibitor combined with
      two nucleoside reverse transcriptase inhibitors is currently the most widely used
      regimen. Among protease inhibitors, lopinavir combined with ritonavir is the most
      frequently used; however, atazanavir combined with ritonavir is a good
      alternative. Elective cesarean section is the best delivery mode for pregnant
      women with viral loads more than 50  copies/ml.

PMID- 23160460
TI  - Canonical Wnt signaling in megakaryocytes regulates proplatelet formation.
AB  - Wnt signaling is involved in numerous aspects of vertebrate development and
      homeostasis, including the formation and function of blood cells. Here, we show
      that canonical and noncanonical Wnt signaling pathways are present and functional
      in megakaryocytes (MKs), with several Wnt effectors displaying MK-restricted
      expression. Using the CHRF288-11 cell line as a model for human MKs, the
      canonical Wnt3a signal was found to induce a time and dose-dependent increase in
      beta-catenin expression. beta-catenin accumulation was inhibited by the canonical
      antagonist dickkopf-1 (DKK1) and by the noncanonical agonist Wnt5a. Whole genome
      expression analysis demonstrated that Wnt3a and Wnt5a regulated distinct patterns
      of gene expression in MKs, and revealed a further interplay between canonical and
      noncanonical Wnt pathways. Fetal liver cells derived from low-density-lipoprotein
      receptor-related protein 6-deficient mice (LRP6(-/-)), generated dramatically
      reduced numbers of MKs in culture of lower ploidy (2N and 4N) than wild-type
      controls, implicating LRP6-dependent Wnt signaling in MK proliferation and
      maturation. Finally, in wild-type mature murine fetal liver-derived MKs, Wnt3a
      potently induced proplatelet formation, an effect that could be completely
      abrogated by DKK1. These data identify novel extrinsic regulators of proplatelet
      formation, and reveal a profound role for Wnt signaling in platelet production.

PMID- 23160461
TI  - Myelopoiesis is regulated by osteocytes through Gsalpha-dependent signaling.
AB  - Hematopoietic progenitors are regulated in their respective niches by cells of
      the bone marrow microenvironment. The bone marrow microenvironment is composed of
      a variety of cell types, and the relative contribution of each of these cells for
      hematopoietic lineage maintenance has remained largely unclear. Osteocytes, the
      most abundant yet least understood cells in bone, are thought to initiate
      adaptive bone remodeling responses via osteoblasts and osteoclasts. Here we
      report that these cells regulate hematopoiesis, constraining myelopoiesis through
      a Gsalpha-mediated mechanism that affects G-CSF production. Mice lacking Gsalpha
      in osteocytes showed a dramatic increase in myeloid cells in bone marrow, spleen,
      and peripheral blood. This hematopoietic phenomenon was neither intrinsic to the
      hematopoietic cells nor dependent on osteoblasts but was a consequence of an
      altered bone marrow microenvironment imposed by Gsalpha deficiency in osteocytes.
      Conditioned media from osteocyte-enriched bone explants significantly increased
      myeloid colony formation in vitro, which was blocked by G-CSF-neutralizing
      antibody, indicating a critical role of osteocyte-derived G-CSF in the myeloid
      expansion.

PMID- 23160463
TI  - Incremental value in outcome prediction with gene expression-based signatures in
      diffuse large B-cell lymphoma.
AB  - Multiple gene expression-based signatures have been identified in diffuse large B
      cell lymphoma that are predictive for survival outcomes. Most studies assess
      predictive significance based on P values from multivariable Cox regression. Few
      investigations have evaluated the incremental usefulness of these signatures.
      Recent developments in statistical methodology extend the use of concordance
      measures on censored survival data. We applied these methods to evaluate the
      added value in survival risk prediction from 3 published gene-based signatures on
      2 sets of patients with diffuse large B-cell lymphoma treated with CHOP or R
      CHOP. Our results indicate these gene-based signatures are inferior to clinical
      factors and provide little added value in risk assessment. To develop highly
      discriminating risk prediction models, we need to use appropriate approaches and
      consider more than gene expression. However, the study of gene expression and
      clinical outcomes retains considerable potential to enhance understanding of
      disease mechanisms and uncover new therapeutic targets.

PMID- 23160462
TI  - inv(16)/t(16;16) acute myeloid leukemia with non-type A CBFB-MYH11 fusions
      associate with distinct clinical and genetic features and lack KIT mutations.
AB  - The inv(16)(p13q22)/t(16;16)(p13;q22) in acute myeloid leukemia results in
      multiple CBFB-MYH11 fusion transcripts, with type A being most frequent. The
      biologic and prognostic implications of different fusions are unclear. We
      analyzed CBFB-MYH11 fusion types in 208 inv(16)/t(16;16) patients with de novo
      disease, and compared clinical and cytogenetic features and the KIT mutation
      status between type A (n = 182; 87%) and non-type A (n = 26; 13%) patients. At
      diagnosis, non-type A patients had lower white blood counts (P = .007), and more
      often trisomies of chromosomes 8 (P = .01) and 21 (P < .001) and less often
      trisomy 22 (P = .02). No patient with non-type A fusion carried a KIT mutation,
      whereas 27% of type A patients did (P = .002). Among the latter, KIT mutations
      conferred adverse prognosis; clinical outcomes of non-type A and type A patients
      with wild-type KIT were similar. We also derived a fusion-type-associated global
      gene-expression profile. Gene Ontology analysis of the differentially expressed
      genes revealed-among others-an enrichment of up-regulated genes involved in
      activation of caspase activity, cell differentiation and cell cycle control in
      non-type A patients. We conclude that non-type A fusions associate with distinct
      clinical and genetic features, including lack of KIT mutations, and a unique gene
      expression profile.

PMID- 23160464
TI  - Distinct severity of HLH in both human and murine mutants with complete loss of
      cytotoxic effector PRF1, RAB27A, and STX11.
AB  - Inherited defects of granule-dependent cytotoxicity led to the life-threatening
      immune disorder hemophagocytic lymphohistiocytosis (HLH), characterized by
      uncontrolled CD8 T-cell and macrophage activation. In a cohort of HLH patients
      with genetic abnormalities expected to result in the complete absence of
      perforin, Rab27a, or syntaxin-11, we found that disease severity as determined by
      age at HLH onset differed significantly, with a severity gradient from perforin
      (early onset) > Rab27a > syntaxin-11 (late onset). In parallel, we have generated
      a syntaxin-11-deficient (Stx11(-/-)) murine model that faithfully reproduced the
      manifestations of HLH after lymphocytic choriomeningitis virus (LCMV) infection.
      Stx11(-/-) murine lymphocytes exhibited a degranulation defect that could be
      rescued by expression of human syntaxin-11 but not expression of a C-terminal
      truncated mutant. Comparison of the characteristics of LCMV infection-induced HLH
      in the murine counterparts of the 3 human conditions revealed a similar gradient
      in the phenotypic severity of HLH manifestations. Strikingly, the severity of HLH
      was not correlated with the LCMV load and not fully with differences in the
      intensity of cytotoxic activity. The capacity of antigen presentation differed in
      vivo between Rab27a- and Syntaxin-11-deficient mutants. Our data indicate that
      cytotoxic effectors may have other immune-regulatory roles in addition to their
      role in controlling viral replication.

PMID- 23160465
TI  - Biologic and clinical significance of somatic mutations of SF3B1 in myeloid and
      lymphoid neoplasms.
AB  - Precursor mRNA splicing is catalyzed by the spliceosome, a macromolecule composed
      of small nuclear RNAs associated with proteins. The SF3B1 gene encodes subunit 1
      of the splicing factor 3b, which is important for anchoring the spliceosome to
      precursor mRNA. In 2011, whole-exome sequencing studies showed recurrent somatic
      mutations of SF3B1 and other genes of the RNA splicing machinery in patients with
      myelodysplastic syndrome or myelodysplastic/myeloproliferative neoplasm. SF3B1
      mutations had a particularly high frequency among conditions characterized by
      ring sideroblasts, which is consistent with a causal relationship. SF3B1 mutants
      were also detected at a lower frequency in a variety of other tumor types. In
      chronic lymphocytic leukemia, SF3B1 was found to be the second most frequently
      mutated gene. In myelodysplastic syndromes, SF3B1 mutations appear to be founding
      genetic lesions and are associated with a low risk of leukemic evolution. In
      contrast, SF3B1 mutations have a lower incidence in early stages of chronic
      lymphocytic leukemia, are more common in advanced disease, and tend to be
      associated with poor prognosis, suggesting that they occur during clonal
      evolution of the disease. The assessment of SF3B1 mutation status may become
      innovative diagnostic and prognostic tools and the availability of spliceosome
      modulators opens novel therapeutic prospects.

PMID- 23160466
TI  - JAK2V617F activates Lu/BCAM-mediated red cell adhesion in polycythemia vera
      through an EpoR-independent Rap1/Akt pathway.
AB  - Polycythemia vera (PV) is characterized by an increased RBC mass, spontaneous
      erythroid colony formation, and the JAK2V617F mutation. PV is associated with a
      high risk of mesenteric and cerebral thrombosis. PV RBC adhesion to endothelial
      laminin is increased and mediated by phosphorylated erythroid Lu/BCAM. In the
      present work, we investigated the mechanism responsible for Lu/BCAM
      phosphorylation in the presence of JAK2V617F using HEL and BaF3 cell lines as
      well as RBCs from patients with PV. High levels of Rap1-GTP were found in HEL and
      BaF3 cells expressing JAK2V617F compared with BaF3 cells with wild-type JAK2.
      This finding was associated with increased Akt activity, Lu/BCAM phosphorylation,
      and cell adhesion to laminin that were inhibited by the dominant-negative
      Rap1S17N or by the specific Rap1 inhibitor GGTI-298. Surprisingly, knocking-down
      EpoR in HEL cells did not alter Akt activity or cell adhesion to laminin. Our
      findings reveal a novel EpoR-independent Rap1/Akt signaling pathway that is
      activated by JAK2V617F in circulating PV RBCs and responsible for Lu/BCAM
      activation. This new characteristic of JAK2V617F could play a critical role in
      initiating abnormal interactions among circulating and endothelial cells in
      patients with PV.

PMID- 23160468
TI  - WT1-specific T-cell responses in high-risk multiple myeloma patients undergoing
      allogeneic T cell-depleted hematopoietic stem cell transplantation and donor
      lymphocyte infusions.
AB  - While the emergence of WT1-specific cytotoxic T lymphocytes (WT1-CTL) has been
      correlated with better relapse-free survival after allogeneic stem cell
      transplantation in patients with myeloid leukemias, little is known about the
      role of these cells in multiple myeloma (MM). We examined the significance of WT1
      CTL responses in patients with relapsed MM and high-risk cytogenetics who were
      undergoing allogeneic T cell-depleted hematopoietic stem cell transplantation
      (alloTCD-HSCT) followed by donor lymphocyte infusions. Of 24 patients evaluated,
      all exhibited WT1-CTL responses before allogeneic transplantation. These T-cell
      frequencies were universally correlated with pretransplantation disease load. Ten
      patients received low-dose donor lymphocyte infusions beginning 5 months after
      transplantation. All patients subsequently developed increments of WT1-CTL
      frequencies that were associated with reduction in specific myeloma markers, in
      the absence of graft-versus-host disease. Immunohistochemical analyses of WT1 and
      CD138 in bone marrow specimens demonstrated consistent coexpression within
      malignant plasma cells. WT1 expression in the bone marrow correlated with disease
      outcome. Our results suggest an association between the emergence of WT1-CTL and
      graft-versus-myeloma effect in patients treated for relapsed MM after alloTCD
      HSCT and donor lymphocyte infusions, supporting the development of adoptive
      immunotherapeutic approaches using WT1-CTL in the treatment of MM.

PMID- 23160467
TI  - The constitutive androstane receptor is a novel therapeutic target facilitating
      cyclophosphamide-based treatment of hematopoietic malignancies.
AB  - Cyclophosphamide (CPA) is one of the most widely used chemotherapeutic prodrugs
      that undergoes hepatic bioactivation mediated predominantly by cytochrome P450
      (CYP) 2B6. Given that the CYP2B6 gene is primarily regulated by the constitutive
      androstane receptor (CAR, NR1I3), we hypothesize that selective activation of CAR
      can enhance systemic exposure of the pharmacologically active 4
      hydroxycyclophosamide (4-OH-CPA), with improved efficacy of CPA-based
      chemotherapy. In this study, we have developed a unique human primary hepatocyte
      (HPH)-leukemia cell coculture model; the chemotherapeutic effects of CPA on
      leukemia cells can be directly investigated in vitro in a cellular environment
      where hepatic metabolism was well maintained. Our results demonstrated that
      activation of CAR preferentially induces the expression of CYP2B6 over CYP3A4 in
      HPHs, although endogenous expression of these enzymes in leukemia cells remains
      negligible. Importantly, coadministration of CPA with a human CAR activator led
      to significantly enhanced cytotoxicity in leukemia cells by inducing the
      apoptosis pathways, without concomitant increase in the off-target
      hepatotoxicity. Associated with the enhanced antitumor activity, a time and
      concentration-dependent increase in 4-OH-CPA formation was observed in the
      coculture system. Together, our findings offer proof of concept that CAR as a
      novel molecular target can facilitate CPA-based chemotherapy by selectively
      promoting its bioactivation.

PMID- 23160469
TI  - Disease-associated missense mutations in the EVH1 domain disrupt intrinsic WASp
      function causing dysregulated actin dynamics and impaired dendritic cell
      migration.
AB  - Wiskott Aldrich syndrome (WAS), an X-linked immunodeficiency, results from loss
      of-function mutations in the human hematopoietic cytoskeletal regulator gene WAS.
      Many missense mutations in the Ena Vasp homology1 (EVH1) domain preserve low
      level WAS protein (WASp) expression and confer a milder clinical phenotype.
      Although disrupted binding to WASp-interacting protein (WIP) leads to enhanced
      WASp degradation in vivo, the intrinsic function of EVH1-mutated WASp is poorly
      understood. In the present study, we show that, despite mediating enhanced actin
      polymerization compared with wild-type WASp in vitro, EVH1 missense mutated
      proteins did not support full biologic function in cells, even when levels were
      restored by forced overexpression. Podosome assembly was aberrant and associated
      with dysregulated lamellipodia formation and impaired persistence of migration.
      At sites of residual podosome-associated actin polymerization, localization of
      EVH1-mutated proteins was preserved even after deletion of the entire domain,
      implying that WIP-WASp complex formation is not absolutely required for WASp
      localization. However, retention of mutant proteins in podosomes was
      significantly impaired and associated with reduced levels of WASp tyrosine
      phosphorylation. Our results indicate that the EVH1 domain is important not only
      for WASp stability, but also for intrinsic biologic activity in vivo.

PMID- 23160470
TI  - IL-7 and IL-15 instruct the generation of human memory stem T cells from naive
      precursors.
AB  - Long-living memory stem T cells (T(SCM)) with the ability to self-renew and the
      plasticity to differentiate into potent effectors could be valuable weapons in
      adoptive T-cell therapy against cancer. Nonetheless, procedures to specifically
      target this T-cell population remain elusive. Here, we show that it is possible
      to differentiate in vitro, expand, and gene modify in clinically compliant
      conditions CD8(+) T(SCM) lymphocytes starting from naive precursors. Requirements
      for the generation of this T-cell subset, described as
      CD62L(+)CCR7(+)CD45RA(+)CD45R0(+)IL-7Ralpha(+)CD95(+), are CD3/CD28 engagement
      and culture with IL-7 and IL-15. Accordingly, T(SCM) accumulates early after
      hematopoietic stem cell transplantation. The gene expression signature and
      functional phenotype define this population as a distinct memory T-lymphocyte
      subset, intermediate between naive and central memory cells. When transplanted in
      immunodeficient mice, gene-modified naive-derived T(SCM) prove superior to other
      memory lymphocytes for the ability to expand and differentiate into effectors
      able to mediate a potent xenogeneic GVHD. Furthermore, gene-modified T(SCM) are
      the only T-cell subset able to expand and mediate GVHD on serial transplantation,
      suggesting self-renewal capacity in a clinically relevant setting. These findings
      provide novel insights into the origin and requirements for T(SCM) generation and
      pave the way for their clinical rapid exploitation in adoptive cell therapy.

PMID- 23160471
TI  - Heat shock protein 70 regulates Tcl1 expression in leukemia and lymphomas.
AB  - T-cell leukemia/lymphoma 1 (TCL1) is an oncogene overexpressed in T-cell
      prolymphocytic leukemia and in B-cell malignancies including B-cell chronic
      lymphocytic leukemia and lymphomas. To date, only a limited number of Tcl1
      interacting proteins that regulate its oncogenic function have been identified.
      Prior studies used a proteomic approach to identify a novel interaction between
      Tcl1 with Ataxia Telangiectasia Mutated. The association of Tcl1 and Ataxia
      Telangiectasia Mutated leads to activation of the NF-kappaB pathway. Here, we
      demonstrate that Tcl1 also interacts with heat shock protein (Hsp) 70. The Tcl1
      Hsp70 complex was validated by coimmunoprecipitation experiments. In addition, we
      report that Hsp70, a protein that plays a critical role in the folding and
      maturation of several oncogenic proteins, associates with Tcl1 protein and
      stabilizes its expression. The inhibition of the ATPase activity of Hsp70 results
      in ubiquitination and proteasome-dependent degradation of Tcl1. The inhibition of
      Hsp70 significantly reduced the growth of lymphoma xenografts in vivo and down
      regulated the expression of Tcl1 protein. Our findings reveal a functional
      interaction between Tcl1 and Hsp70 and identify Tcl1 as a novel Hsp70 client
      protein. These findings suggest that inhibition of Hsp70 may represent an
      alternative effective therapy for chronic lymphocytic leukemia and lymphomas via
      its ability to inhibit the oncogenic functions of Tcl1.

PMID- 23160473
TI  - Accelerated evaluation of the robustness of treatment plans against geometric
      uncertainties by Gaussian processes.
AB  - In order to provide a consistently high quality treatment, it is of great
      interest to assess the robustness of a treatment plan under the influence of
      geometric uncertainties. One possible method to implement this is to run
      treatment simulations for all scenarios that may arise from these uncertainties.
      These simulations may be evaluated in terms of the statistical distribution of
      the outcomes (as given by various dosimetric quality metrics) or statistical
      moments thereof, e.g. mean and/or variance. This paper introduces a method to
      compute the outcome distribution and all associated values of interest in a very
      efficient manner. This is accomplished by substituting the original patient model
      with a surrogate provided by a machine learning algorithm. This Gaussian process
      (GP) is trained to mimic the behavior of the patient model based on only very few
      samples. Once trained, the GP surrogate takes the place of the patient model in
      all subsequent calculations.The approach is demonstrated on two examples. The
      achieved computational speedup is more than one order of magnitude.

PMID- 23160472
TI  - Regulatory T cells are strong promoters of acute ischemic stroke in mice by
      inducing dysfunction of the cerebral microvasculature.
AB  - We have recently identified T cells as important mediators of ischemic brain
      damage, but the contribution of the different T-cell subsets is unclear. Forkhead
      box P3 (FoxP3)-positive regulatory T cells (Tregs) are generally regarded as
      prototypic anti-inflammatory cells that maintain immune tolerance and counteract
      tissue damage in a variety of immune-mediated disorders. In the present study, we
      examined the role of Tregs after experimental brain ischemia/reperfusion injury.
      Selective depletion of Tregs in the DEREG mouse model dramatically reduced
      infarct size and improved neurologic function 24 hours after stroke and this
      protective effect was preserved at later stages of infarct development. The
      specificity of this detrimental Treg effect was confirmed by adoptive transfer
      experiments in wild-type mice and in Rag1(-/-) mice lacking lymphocytes.
      Mechanistically, Tregs induced microvascular dysfunction in vivo by increased
      interaction with the ischemic brain endothelium via the LFA-1/ICAM-1 pathway and
      platelets and these findings were confirmed in vitro. Ablation of Tregs reduced
      microvascular thrombus formation and improved cerebral reperfusion on stroke, as
      revealed by ultra-high-field magnetic resonance imaging at 17.6 Tesla. In
      contrast, established immunoregulatory characteristics of Tregs had no functional
      relevance. We define herein a novel and unexpected role of Tregs in a primary
      nonimmunologic disease state.

PMID- 23160474
TI  - Comparison of ultrasound attenuation and backscatter estimates in layered tissue
      mimicking phantoms among three clinical scanners.
AB  - Backscatter and attenuation coefficient estimates are needed in many quantitative
      ultrasound strategies. In clinical applications, these parameters may not be
      easily obtained because of variations in scattering by tissues overlying a region
      of interest (ROI). The goal of this study is to assess the accuracy of
      backscatter and attenuation estimates for regions distal to nonuniform layers of
      tissue-mimicking materials. In addition, this work compares results of these
      estimates for "layered" phantoms scanned using different clinical ultrasound
      machines. Two tissue-mimicking phantoms were constructed, each exhibiting depth
      dependent variations in attenuation or backscatter. The phantoms were scanned
      with three ultrasound imaging systems, acquiring radio frequency echo data for
      offline analysis. The attenuation coefficient and the backscatter coefficient
      (BSC) for sections of the phantoms were estimated using the reference phantom
      method. Properties of each layer were also measured with laboratory techniques on
      test samples manufactured during the construction of the phantom. Estimates of
      the attenuation coefficient versus frequency slope, alpha(0), using backscatter
      data from the different systems agreed to within 0.24 dB/cm-MHz. Bias in the
      alpha(0) estimates varied with the location of the ROI. BSC estimates for phantom
      sections whose locations ranged from 0 to 7 cm from the transducer agreed among
      the different systems and with theoretical predictions, with a mean bias error of
      1.01 dB over the used bandwidths. This study demonstrates that attenuation and
      BSCs can be accurately estimated in layered inhomogeneous media using pulse-echo
      data from clinical imaging systems.

PMID- 23160475
TI  - In vivo classification of breast masses using features derived from axial-strain
      and axial-shear images.
AB  - Breast cancer is currently the second leading cause of cancer deaths in women.
      Early detection and accurate classification of suspicious masses as benign or
      malignant is important for arriving at an appropriate treatment plan. In this
      article, we present classification results for features extracted from ultrasound
      based, axial-strain and axial-shear images of breast masses. The breast-mass
      stiffness contrast, size ratio, and a normalized axial-shear strain area feature
      are evaluated for the classification of in vivo breast masses using a leave-one
      out classifier. Radiofrequency echo data from 123 patients were acquired using
      Siemens Antares or Elegra clinical ultrasound systems during freehand palpation.
      Data from four different institutions were analyzed. Axial displacements and
      strains were estimated using a multilevel, pyramid-based two-dimensional cross
      correlation algorithm, with final processing block dimensions of 0.385 mm * 0.507
      mm (three A-lines). Since mass boundaries on B-mode images for 21 patients could
      not be delineated (isoechoic), the combined feature analysis was only performed
      for 102 patients. Results from receiver operating characteristic (ROC)
      demonstrate that the area under the curve was 0.90, 0.84, and 0.52 for the
      normalized axial-shear strain, size ratio, and stiffness contrast, respectively.
      When these three features were combined using a leave-one-out classifier and
      support vector machine approach, the overall area under the curve improved to
      0.93.

PMID- 23160476
TI  - Rapid transient pressure field computations in the nearfield of circular
      transducers using frequency-domain time-space decomposition.
AB  - The fast nearfield method, when combined with time-space decomposition, is a
      rapid and accurate approach for calculating transient nearfield pressures
      generated by ultrasound transducers. However, the standard time-space
      decomposition approach is only applicable to certain analytical representations
      of the temporal transducer surface velocity that, when applied to the fast
      nearfield method, are expressed as a finite sum of products of separate temporal
      and spatial terms. To extend time-space decomposition such that accelerated
      transient field simulations are enabled in the nearfield for an arbitrary
      transducer surface velocity, a new transient simulation method, frequency-domain
      time-space decomposition (FDTSD), is derived. With this method, the temporal
      transducer surface velocity is transformed into the frequency domain, and then
      each complex-valued term is processed separately. Further improvements are
      achieved by spectral clipping, which reduces the number of terms and the
      computation time. Trade-offs between speed and accuracy are established for FDTSD
      calculations, and pressure fields obtained with the FDTSD method for a circular
      transducer are compared with those obtained with Field II and the impulse
      response method. The FDTSD approach, when combined with the fast nearfield method
      and spectral clipping, consistently achieves smaller errors in less time and
      requires less memory than Field II or the impulse response method.

PMID- 23160479
TI  - Temporal role of Sertoli cell androgen receptor expression in spermatogenic
      development.
AB  - Sertoli cell (SC) androgen receptor (AR) activity is vital for spermatogenesis.
      We created a unique gain-of-function transgenic (Tg) mouse model to determine the
      temporal role of SCAR expression in testicular development. The SC-specific rat
      Abpa promoter directed human Tg AR [Tg SC-specific AR (TgSCAR)] expression,
      providing strong premature postnatal AR immunolocalized to SC nuclei. Independent
      Tg lines revealed that TgSCAR dose dependently reduced postnatal and mature
      testis size (to 60% normal), whereas androgen-dependent mature seminal vesicle
      weights and serum testosterone levels remained normal. Total SC numbers were
      reduced in developing and mature TgSCAR testes, despite normal or higher Fshr
      mRNA and circulating FSH levels. Postnatal TgSCAR testes exhibited elevated
      levels of AR-regulated Rhox5 and Spinlw1 transcripts, and precocious SC function
      was demonstrated by early seminiferous tubular lumen formation and up-regulated
      expression of crucial SC tight-junction (Cldn11 and Tjp1) and phagocytic (Elmo1)
      transcripts. Early postnatal Amh expression was elevated but declined to normal
      levels in peripubertal-pubertal TgSCAR vs. control testes, indicating
      differential age-related regulation featuring AR-independent Amh down-regulation.
      TgSCAR induced premature postnatal spermatogenic development, shown by increased
      levels of meiotic (Dmc1 and Spo11) and postmeiotic (Capza3 and Prm1) germ cell
      transcripts, elevated meiotic-postmeiotic germ:Sertoli cell ratios, and
      accelerated spermatid development. Meiotic germ:Sertoli cell ratios were further
      increased in adult TgSCAR mice, indicating predominant SCAR-mediated control of
      meiotic development. However, postmeiotic germ:Sertoli cell ratios declined below
      normal. Our unique TgSCAR paradigm reveals that atypical SC-specific temporal AR
      expression provides a direct molecular mechanism for induction of precocious
      testicular development, leading to reduced adult testis size and decreased
      postmeiotic development.

PMID- 23160480
TI  - Severe growth deficiency is associated with STAT5b mutations that disrupt protein
      folding and activity.
AB  - The first genetic defect in human signal transducer and activator of
      transcription (STAT)5b was identified in an individual with profound short
      stature and GH insensitivity, immune dysfunction, and severe pulmonary disease,
      and was caused by an alanine to proline substitution (A630P) within the Src
      homology-2 (SH2) domain. STAT5b(A630P) was found to be an inactive transcription
      factor based on its aberrant folding, diminished solubility, and propensity for
      aggregation triggered by its misfolded SH2 domain. Here we have characterized the
      second human STAT5b amino acid substitution mutation in an individual with
      similar pathophysiological features. This single nucleotide transition, predicted
      to change phenyalanine 646 to serine (F646S), also maps to the SH2 domain. Like
      STAT5b(A630P), STAT5b(F646S) is prone to aggregation, as evidenced by its
      detection in the insoluble fraction of cell extracts, the presence of dimers and
      higher-order oligomers in the soluble fraction, and formation of insoluble
      cytoplasmic inclusion bodies in cells. Unlike STAT5b(A630P), which showed minimal
      GH-induced tyrosine phosphorylation and no transcriptional activity,
      STAT5b(F646S) became tyrosine phosphorylated after GH treatment and could
      function as a GH-activated transcription factor, although to a substantially
      lesser extent than STAT5b(WT). Biochemical characterization demonstrated that the
      isolated SH2 domain containing the F646S substitution closely resembled the wild
      type SH2 domain in secondary structure, but exhibited reduced thermodynamic
      stability and altered tertiary structure that were intermediate between
      STAT5b(A630P) and STAT5b(WT). Homology-based structural modeling suggests that
      the F646S mutation disrupts key hydrophobic interactions and may also distort the
      phosphopeptide-binding face of the SH2 domain, explaining both the reduced
      thermodynamic stability and impaired biological activity.

PMID- 23160482
TI  - Management of pancreatic intraductal papillary mucinous neoplasm in an academic
      hospital (2005-2010): what follow-up for unoperated patients?
AB  - OBJECTIVES: Intraductal papillary mucinous neoplasms (IPMNs) of the pancreas are
      diagnosed frequently in asymptomatic patients. It is still not clear what follow
      up is indicated for patients not undergoing surgical resection. METHODS: Review
      of all reports of magnetic resonance cholangiopancreatography (MRCP) from June
      2005 to June 2010, identifying all patients diagnosed with IPMN; subsequent
      reconstruction of the initial therapeutic decision, indications for and adherence
      to scheduled follow-up, and IPMN evolution by morphology and by biology. RESULTS:
      Overall, 4943 MRCP reports were analyzed, identifying 234 patients with IPMN.
      Although 143 (61.1%) of these were comprised in Sendai criteria for resection,
      surgical resection was considered in only 42 (17.9%) patients. Of the remainder,
      52 were not subjected to any control, 58 to a single short time check, 77 to MRCP
      based regular annual follow-up, and 5 were treated for associated ductal
      adenocarcinoma. With a median follow-up of 39.5 months (range, 12-72), 37.6% of
      125 patients in follow-up had a morphological evolution, but only 2.4% has
      developed a malignant IPMN. No deaths were recorded, directly related to IPMN, in
      all 187 conservatively managed patients. CONCLUSIONS: In the analyzed series,
      fewer patients than expected underwent surgical resection, and only 67.2% undergo
      regular follow-up, but no more than 2.4% developed malignancy.

PMID- 23160481
TI  - FOXO1 controls thyroid cell proliferation in response to TSH and IGF-I and is
      involved in thyroid tumorigenesis.
AB  - TSH and insulin/IGF-I synergistically induce the proliferation of thyroid cells
      mainly through the cAMP and phosphatidylinositol 3-kinase (PI3K) pathways.
      However, the events involved in this cooperative induction remain unknown, and
      molecules that are potentially controlled by both TSH and IGF-I are interesting
      candidates as integrators of both stimuli. The finding that the PI3K pathway is
      frequently activated in thyroid malignancies has attracted attention to this
      pathway in the thyroid field. One of the targets of PI3K is Forkhead box O (FoxO)
      1, a widely expressed transcription factor involved in a variety of cellular
      processes such as differentiation, proliferation, and apoptosis. Here we show
      that FoxO1 is highly expressed in differentiated rat thyroid cells and human
      thyroid tissue compared with human thyroid tumor-derived cells and surgically
      removed thyroid tumors, in which its expression is reduced. In differentiated
      cells, TSH/cAMP treatment decreases FoxO1 mRNA and protein levels through
      proteasome activation, whereas both TSH and IGF-I control FoxO1 localization by
      promoting a rapid exclusion from the nucleus in an Akt-dependent manner. FoxO1
      can control p27(KIP1) expression in differentiated and tumor cells of the
      thyroid. Furthermore, FoxO1 reexpression in tumor cells promotes a decrease in
      their proliferation rate, whereas FoxO1 interference in differentiated cells
      increases their proliferation. These data point to an important role of FoxO1 in
      mediating the effects of TSH and IGF-I on thyroid cell proliferation and provide
      a link between loss of FoxO1 expression and the uncontrolled proliferation of
      thyroid tumor cells.

PMID- 23160483
TI  - A single fasting plasma 5-HIAA value correlates with 24-hour urinary 5-HIAA
      values and other biomarkers in midgut neuroendocrine tumors (NETs).
AB  - OBJECTIVES: 5-Hydroxyindoleacetic acid (5-HIAA) is used for the evaluation of
      neuroendocrine tumors (NETs) but currently requires a 24-hour urine collection.
      METHODS: We developed a gas chromatography mass spectroscopy-based plasma 5-HIAA
      assay. We compared 24-hour urine 5-HIAA values against plasma 5-HIAA values in
      115 mixed-variety patients with NETs and in a subset of 72 patients with only
      small bowel NETs. We also compared the information gained from urinary and plasma
      5-HIAA values with other biomarkers of midgut NET activity to determine the
      plasma assay's clinical implications. RESULTS: In a group of 115 patients with
      all types of NETS, in a subset of patients with midgut NET and in a subgroup of
      midgut NETS with liver metastasis, the correlation between the urine and fasting
      plasma 5-HIAA values were statistically significant (P <= 0.0001). Comparison of
      the proportion of normal or abnormal urinary and plasma 5-HIAA values to the
      proportion of chromogranin, serotonin, neurokinin, or pancreastatin values that
      were in the normal or abnormal range yielded essentially identical information.
      CONCLUSIONS: Plasma fasting 5-HIAA values are proportional to urinary 5-HIAA
      values and yielded identical clinical correlation with other biomarkers.

PMID- 23160484
TI  - A new series of bis(ene-1,2-dithiolato)tungsten(IV), -(V), -(VI) complexes as
      reaction centre models of tungsten enzymes: preparation, crystal structures and
      spectroscopic properties.
AB  - The carbomethoxy substituted dithiolene ligand (L(COOMe)) enabled us to develop a
      series of new bis(ene-1,2-dithiolato)tungsten complexes including W(IV)O,
      W(IV)(OSiBuPh(2)), W(VI)O(2), W(VI)O(OSiBuPh(2)) and W(VI)O(S) core structures.
      By using these tungsten complexes, a systematic study of the terminal monodentate
      ligand effects has been performed on the structural, spectroscopic properties and
      reactivity. The structure and spectroscopic properties of the tungsten complexes
      have also been compared to those of the molybdenum complexes coordinated by the
      same ligand to investigate the effects of the metal ion (W vs. Mo). X-ray
      crystallographic analyses of the tungsten(IV) complexes have revealed that the
      tungsten centres adopt a distorted square pyramidal geometry with a dithiolene
      ligand having an ene-1,2-dithiolate form. On the other hand, the
      dioxotungsten(VI) complex exhibits an octahedral structure consisting of the
      bidentate L(COOMe) and two oxo groups, in which pi-delocalization was observed
      between the W(VI)O(2) and ene-1,2-dithiolate units. The tungsten(IV) and
      dioxotungsten(VI) complexes are isostructural with the molybdenum counter parts.
      DFT calculation study of the W(VI)O(S) complex has indicated that the W=S bond of
      2.2 A is close to the bond length between the tungsten centre and ambiguously
      assigned terminal monodentate atom in aldehyde oxidoreductase of the tungsten
      enzyme. Resonance Raman (rR) spectrum of the W(VI)O(S) complex has shown the two
      inequivalent L(COOMe) ligands with respect to their bonding interactions with the
      tungsten centre, reproducing the appearance of two nu(C=C) stretches in the rR
      spectrum of aldehyde oxidoreductase. Sulfur atom transfer reaction from the
      W(VI)O(S) complex to triphenylphosphines has also been studied kinetically to
      demonstrate that the tungsten complex has a lower reactivity by about one-order
      of magnitude, when compared with its molybdenum counterpart.

PMID- 23160485
TI  - Maternal ADHD, Parenting, and Psychopathology Among Mothers of Adolescents With
      ADHD.
AB  - OBJECTIVE: This study describes the parenting and psychopathology of mothers with
      ADHD of adolescents with ADHD (MCA), non-ADHD mothers of adolescents with ADHD
      (CA), and non-ADHD mothers of adolescents without ADHD (COMP). METHOD: Two sets
      of pairwise comparisons: (a) COMP versus CA and (b) CA versus MCA were conducted.
      We hypothesized that CA would experience greater distress in parenting and
      psychopathology compared with COMP and that MCA would experience even more
      impairment compared with CA. RESULTS: Few differences emerged in comparisons of
      CA and COMP, with the exception of CA reporting greater parent-adolescent
      conflict and internalizing problems. In contrast, differences consistently
      emerged in comparisons of MCA and CA showing more difficulty for MCA in parenting
      and psychopathology. CONCLUSION: These findings underscore the need for
      treatments that address parental ADHD when adolescent ADHD is the intended
      target.

PMID- 23160486
TI  - Persistent Handwriting Difficulties in Children With ADHD After Treatment With
      Stimulant Medication.
AB  - OBJECTIVE: Children with ADHD often present with handwriting difficulties.
      However, the extent to which motor and attention skills influence performance in
      this group has not yet been explored. The objective of this study was to examine
      the factors associated with change in handwriting performance. METHOD: This study
      examines the factors associated with change in handwriting performance of 49
      children newly diagnosed with ADHD (mean age = 8.4 [SD=1.3] years) prior to and 3
      months following use of a stimulant medication. RESULTS: Handwriting legibility
      and speed improved significantly at follow-up evaluation. However, most of the
      children with legibility difficulties at baseline continued to demonstrate
      difficulties when evaluated 3 months after initiation of medication. Change in
      handwriting legibility was best determined by improvements in visual-motor
      integration skills (beta = 0.07-0.10; p < .001), while the change in speed did
      not appear to be consistently related to a single factor. CONCLUSION: Handwriting
      difficulties are common in children with ADHD, and medication alone is not
      sufficient to resolve these challenges.

PMID- 23160487
TI  - Co-Occurrence of ADHD and Anxiety in Preschool Children.
AB  - OBJECTIVE: The objective of this study was to examine co-occurrence of ADHD and
      anxiety in preschool children. METHOD: The data collection was part of the
      Norwegian Mother and Child Cohort Study (MoBa) at the Norwegian Institute of
      Public Health. After a screening for ADHD symptoms at 36 months, participants
      were clinically assessed at age 36 to 44 months. Psychiatric symptoms of ADHD and
      anxiety were derived from the Preschool Age Psychiatric Assessment (PAPA)
      interview. RESULTS: In preschoolers with ADHD symptoms, 33% were reported to have
      symptoms of anxiety. Children with symptoms of ADHD and anxiety had more severe
      ADHD symptomatology, and particularly more inattentive symptoms compared with
      children with ADHD symptoms and no anxiety. CONCLUSION: Clinicians should be
      aware of the frequent overlap between symptoms of anxiety and ADHD in
      preschoolers as different intervention strategies may be required.

PMID- 23160488
TI  - Efficacy of Polyunsaturated Fatty Acids (PUFA) in the Treatment of Attention
      Deficit Hyperactivity Disorder.
AB  - OBJECTIVE: We aimed to investigate the efficacy of polyunsaturated fatty acids
      (PUFAs) as an adjuvant treatment in patients with ADHD receiving methylphenidate
      as well as its side effects. METHOD: This randomized clinical trial was conducted
      on 40 ADHD patients aged between 6 and 12 years. Both treatment and placebo
      groups received methylphenidate. Treatment arm also received omega-6 once daily.
      The Parent ADHD Rating Scale was used to evaluate disease improvement. RESULTS:
      The Parent ADHD Rating Scale scores of the two groups were similar at baseline.
      Although total score and scores of three categories decreased significantly in
      both groups, total score and scores of inattention, hyperactivity, and
      impulsivity were not significantly different between the groups. CONCLUSION: The
      results did not support the efficacy of PUFA in the treatment of ADHD, and adding
      PUFAs to the therapeutic regimen of ADHD is not recommended at the moment.

PMID- 23160490
TI  - Somatic copy number mosaicism in human skin revealed by induced pluripotent stem
      cells.
AB  - Reprogramming somatic cells into induced pluripotent stem cells (iPSCs) has been
      suspected of causing de novo copy number variation. To explore this issue, here
      we perform a whole-genome and transcriptome analysis of 20 human iPSC lines
      derived from the primary skin fibroblasts of seven individuals using next
      generation sequencing. We find that, on average, an iPSC line manifests two copy
      number variants (CNVs) not apparent in the fibroblasts from which the iPSC was
      derived. Using PCR and digital droplet PCR, we show that at least 50% of those
      CNVs are present as low-frequency somatic genomic variants in parental
      fibroblasts (that is, the fibroblasts from which each corresponding human iPSC
      line is derived), and are manifested in iPSC lines owing to their clonal origin.
      Hence, reprogramming does not necessarily lead to de novo CNVs in iPSCs, because
      most of the line-manifested CNVs reflect somatic mosaicism in the human skin.
      Moreover, our findings demonstrate that clonal expansion, and iPSC lines in
      particular, can be used as a discovery tool to reliably detect low-frequency CNVs
      in the tissue of origin. Overall, we estimate that approximately 30% of the
      fibroblast cells have somatic CNVs in their genomes, suggesting widespread
      somatic mosaicism in the human body. Our study paves the way to understanding the
      fundamental question of the extent to which cells of the human body normally
      acquire structural alterations in their DNA post-zygotically.

PMID- 23160491
TI  - Fucose sensing regulates bacterial intestinal colonization.
AB  - The mammalian gastrointestinal tract provides a complex and competitive
      environment for the microbiota. Successful colonization by pathogens requires
      scavenging nutrients, sensing chemical signals, competing with the resident
      bacteria and precisely regulating the expression of virulence genes. The
      gastrointestinal pathogen enterohaemorrhagic Escherichia coli (EHEC) relies on
      inter-kingdom chemical sensing systems to regulate virulence gene expression.
      Here we show that these systems control the expression of a novel two-component
      signal transduction system, named FusKR, where FusK is the histidine sensor
      kinase and FusR the response regulator. FusK senses fucose and controls
      expression of virulence and metabolic genes. This fucose-sensing system is
      required for robust EHEC colonization of the mammalian intestine. Fucose is
      highly abundant in the intestine. Bacteroides thetaiotaomicron produces multiple
      fucosidases that cleave fucose from host glycans, resulting in high fucose
      availability in the gut lumen. During growth in mucin, B. thetaiotaomicron
      contributes to EHEC virulence by cleaving fucose from mucin, thereby activating
      the FusKR signalling cascade, modulating the virulence gene expression of EHEC.
      Our findings suggest that EHEC uses fucose, a host-derived signal made available
      by the microbiota, to modulate EHEC pathogenicity and metabolism.

PMID- 23160492
TI  - Flickering gives early warning signals of a critical transition to a eutrophic
      lake state.
AB  - There is a recognized need to anticipate tipping points, or critical transitions,
      in social-ecological systems. Studies of mathematical and experimental systems
      have shown that systems may 'wobble' before a critical transition. Such early
      warning signals may be due to the phenomenon of critical slowing down, which
      causes a system to recover slowly from small impacts, or to a flickering
      phenomenon, which causes a system to switch back and forth between alternative
      states in response to relatively large impacts. Such signals for transitions in
      social-ecological systems have rarely been observed, not the least because high
      resolution time series are normally required. Here we combine empirical data from
      a lake-catchment system with a mathematical model and show that flickering can be
      detected from sparse data. We show how rising variance coupled to decreasing
      autocorrelation and skewness started 10-30 years before the transition to
      eutrophic lake conditions in both the empirical records and the model output, a
      finding that is consistent with flickering rather than critical slowing down. Our
      results suggest that if environmental regimes are sufficiently affected by large
      external impacts that flickering is induced, then early warning signals of
      transitions in modern social-ecological systems may be stronger, and hence easier
      to identify, than previously thought.

PMID- 23160495
TI  - Foreword--Ten years at the head of Padua's Geriatric Department.

PMID- 23160493
TI  - DNA-repair scaffolds dampen checkpoint signalling by counteracting the adaptor
      Rad9.
AB  - In response to genotoxic stress, a transient arrest in cell-cycle progression
      enforced by the DNA-damage checkpoint (DDC) signalling pathway positively
      contributes to genome maintenance. Because hyperactivated DDC signalling can lead
      to a persistent and detrimental cell-cycle arrest, cells must tightly regulate
      the activity of the kinases involved in this pathway. Despite their importance,
      the mechanisms for monitoring and modulating DDC signalling are not fully
      understood. Here we show that the DNA-repair scaffolding proteins Slx4 and Rtt107
      prevent the aberrant hyperactivation of DDC signalling by lesions that are
      generated during DNA replication in Saccharomyces cerevisiae. On replication
      stress, cells lacking Slx4 or Rtt107 show hyperactivation of the downstream DDC
      kinase Rad53, whereas activation of the upstream DDC kinase Mec1 remains normal.
      An Slx4-Rtt107 complex counteracts the checkpoint adaptor Rad9 by physically
      interacting with Dpb11 and phosphorylated histone H2A, two positive regulators of
      Rad9-dependent Rad53 activation. A decrease in DDC signalling results from
      hypomorphic mutations in RAD53 and H2A and rescues the hypersensitivity to
      replication stress of cells lacking Slx4 or Rtt107. We propose that the Slx4
      Rtt107 complex modulates Rad53 activation by a competition-based mechanism that
      balances the engagement of Rad9 at replication-induced lesions. Our findings show
      that DDC signalling is monitored and modulated through the direct action of DNA
      repair factors.

PMID- 23160494
TI  - A prefrontal cortex-brainstem neuronal projection that controls response to
      behavioural challenge.
AB  - The prefrontal cortex (PFC) is thought to participate in high-level control of
      the generation of behaviours (including the decision to execute actions); indeed,
      imaging and lesion studies in human beings have revealed that PFC dysfunction can
      lead to either impulsive states with increased tendency to initiate action, or to
      amotivational states characterized by symptoms such as reduced activity,
      hopelessness and depressed mood. Considering the opposite valence of these two
      phenotypes as well as the broad complexity of other tasks attributed to PFC, we
      sought to elucidate the PFC circuitry that favours effortful behavioural
      responses to challenging situations. Here we develop and use a quantitative
      method for the continuous assessment and control of active response to a
      behavioural challenge, synchronized with single-unit electrophysiology and
      optogenetics in freely moving rats. In recording from the medial PFC (mPFC), we
      observed that many neurons were not simply movement-related in their spike-firing
      patterns but instead were selectively modulated from moment to moment, according
      to the animal's decision to act in a challenging situation. Surprisingly, we next
      found that direct activation of principal neurons in the mPFC had no detectable
      causal effect on this behaviour. We tested whether this behaviour could be
      causally mediated by only a subclass of mPFC cells defined by specific downstream
      wiring. Indeed, by leveraging optogenetic projection-targeting to control cells
      with specific efferent wiring patterns, we found that selective activation of
      those mPFC cells projecting to the brainstem dorsal raphe nucleus (DRN), a
      serotonergic nucleus implicated in major depressive disorder, induced a profound,
      rapid and reversible effect on selection of the active behavioural state. These
      results may be of importance in understanding the neural circuitry underlying
      normal and pathological patterns of action selection and motivation in behaviour.

PMID- 23160496
TI  - N0 Stage colon cancer: prognostic role of age in relation to tumor site.
AB  - This work investigates the prognostic role of advanced age as a risk factor for
      recurrence in a population of patients undergoing surgery for N0 stage colon
      cancer, and also evaluates whether that role is affected by tumor location. A
      population of 129 consecutive patients who underwent radical surgery for N0 stage
      colon cancer was selected. Patients were subdivided into three age groups: <65,
      65-80 and >80. The only correlation found in the examined population between age
      and clinical-pathological features was between advanced age (>80) and tumor
      location in the right side of the colon. Overall survival (OS) and disease- free
      survival (DFS) were significantly lower in patients over 80 than in the other two
      classes. Two multivariate analyses were carried out: when tumor location was not
      considered, age >80 represented a negative prognostic factor for risk of
      recurrence, regardless of the other factors examined. This role was also
      confirmed when tumor location was considered. As hypothesized by several authors,
      the role of advanced age which emerges from this study is mainly due to the
      increased fragility of elderly patients caused by multiple pathophysiological
      factors, but it does not necessarily represent an absolute contraindication to
      surgery. The role played by tumor location remains controversial, as more and
      more studies show that right colon cancer (RCC) is a biological entity distinct
      from left colon cancer (LCC). Further studies are required to examine right and
      left colon cancers as two separate diseases.

PMID- 23160497
TI  - Choices in surgical treatment of diverticulitis.
AB  - Complications after surgical treatment of diverticulitis are not very frequent,
      in view of the total number of patients affected by this pathology, but they do
      become significant in absolute terms because of the high prevalence of the
      disease itself. Surgeons continue to debate which option is better: Hartmann
      resection or combined resection and anastomosis. Since age is a crucial factor
      when surgery is being considered, we evaluated the outcome of surgical treatment
      for diverticulitis in patients treated in our unit over a six-month period, in
      view of the number of elderly patients generally admitted. Between January 2001
      and June 2012, 77 patients underwent surgery for diverticular disease in the
      Geriatric Surgery Unit of the Department of Surgical and Gastroenterological
      Sciences, University of Padova Hospital. Gastrointestinal resection and
      anastomosis were performed in 75 patients (97%), resulting in an overall
      complication rate of 37% and a mortality rate of 1%. This surgical strategy was
      chosen because, when it is performed by experienced surgeons, it offers the same
      results in terms of mortality and morbidity as Hartmann resection, while
      presenting significant advantages as regards the patient's quality of life.
      Various factors such as the timing of surgery, severity of the disease defined
      according to the Hinchey classification, patient's clinical condition, and
      surgeon's experience and expertise can all influence the surgical choice. Several
      studies in the literature confirm that combined resection and anastomosis is safe
      and efficacious, but more research is needed to confirm these data.

PMID- 23160498
TI  - Current practice in colonoscopy in the elderly.
AB  - Colonoscopy in the elderly is a reliable practice of great diagnostic and
      management value. However, patient's age has long been considered to affect the
      success of the procedure, achieved when the cecum is intubated, there is a good
      view of the colon if preparation has been properly carried out, and the
      examination does not cause excessive discomfort or complications. Substantial
      improvements have been made to the latter two aspects, due to more widespread use
      of deep sedation with propofol and cardiocirculatory monitoring during the
      procedure. The aim of our work was to assess whether, in the everyday practice of
      an open-access, digestive endoscopy teaching center, staffed by various providers
      delivering screening for polyposis, age is still a limitation to the success of
      the procedure and whether appropriate measures have been taken to improve
      colonoscopy in geriatric patients. We analysed 1480 consecutive colonoscopies, of
      which 319 were performed in patients aged over 73 years. The examination was
      significantly less successful in this group of patients (88.1 vs 94.4, p=0.0001),
      but there were no major technical or use-related complications connected with
      administration of propofol for sedation purposes, despite lower doses to the
      elderly (2.2 +/- 1.1 mg/kg total dose, mean 151 +/- 72.4 mg vs 2.9 +/- 1.3 mg/kg
      total dose, mean 199 +/- 77.9 mg in younger patients, p<0.001). More experienced
      technical staff were not allocated to these colonoscopies (for endoscopic or
      anesthesiological purposes) and, according to the results of multivariate
      stepwise logistic regression analysis, inadequate preparation was the main factor
      affecting the success of the procedure in elderly patients (OR 5.9, 95% CI 2.25
      15.72; p=0.0003). Only body weight over 60 kg facilitated it (weight >= 60 kg, OR
      0.46, 95% CI 0.26-0.83). In colonoscopy in the elderly, safety appears to be the
      primary concern and, good outcomes can be achieved, but sometimes at the expense
      of diagnostic accuracy. This could probably be improved through better pre- and
      post-procedure care, not currently differentiated between young and elderly
      patients.

PMID- 23160499
TI  - Effects of 21 months of cholinesterase inhibitors on cognitive and functional
      decline in demented patients.
AB  - AIMS: The aim of this study was to assess, in a natural setting, the development
      of cognitive, behavioral and functional performance of elderly dementia patients
      treated with cholinesterase inhibitors (ChEIs) during a 21-month follow-up.
      Another aim was to compare patterns of clinical changes in relation to patients'
      level of cognitive impairment at the beginning of therapy. METHOD: Of the 1987
      elderly demented patients seen at our unit, 143 met the inclusion/ exclusion
      criteria, were followed for at least 21 months, and were thus included in the
      study. At baseline and each control point (up to 21 months), patients were scored
      for Mini Mental State Examination (MMSE), Activities of Daily Living (ADL) and
      Instrumental Activities of Daily Living (IADL). RESULTS: After 21 months'
      treatment with ChEIs, patients showed a significant reduction in MMSE, ADL and
      IADL values. The MMSE score decreased by 1.7 points/year (95% CI -2.1; -1.3),
      irrespective of initial cognitive level, and was lower than that expected in non
      treated patients (-3/-4 points/year). CONCLUSION: ChEI therapy is effective in
      slowing the progression of dementia, even in the long term, irrespective of
      baseline cognitive level.

PMID- 23160500
TI  - Diabetes in a geriatric ward: efficacy and safety of new insulin analogs in very
      old inpatients.
AB  - AIMS: 1) to evaluate the prevalence of diabetes mellitus (DM) in a geriatric
      ward; 2) to assess the efficacy and safety of insulin analogs in elderly
      inpatients over 65 years of age. METHODS: We analysed the medical records of 1851
      elderly inpatients admitted to our geriatric clinic from March 2009 to September
      2011, to identify patients with DM. The efficacy and safety of insulin analogs
      were measured in patients with a hospital stay of at least 9 days, by assessing
      the means of all glycemic sticks (4-7 sticks/day), number of hyperglycemic events
      (>250 mg/dL) and number of hypoglycemic events (<70 mg/dL) daily. RESULTS: DM
      prevalence was 25% (463/1851). Diabetic patients' mean age was 82.9 +/- 7.5
      years. DM mortality during hospital stay was 10.8% vs 6.7% for non-diabetics
      (p<0.05). 206/463 diabetic inpatients were treated with insulin, and 85.9% of
      them received analogs (Rapid and Longer-Acting). Decreases in mean daily glycemia
      values (from 218.8 +/- 81.6 mg/dL to 170.9 +/- 42.9 mg/dL, p<0.001) and in number
      of hyperglycemic events (from 118 to 47) (p<0.012) were noted in 128 insulin
      analog-treated patients over the 9-day hospitalization. Only 35 hypoglycemic
      events were found out of 4745 sticks (0.7%). CONCLUSIONS: 1) DM prevalence and
      mortality in our very old inpatients are high and similar to data reported in the
      literature. 2) Insulin therapy with analogs is effective (achieves good glycemic
      control) and safe (low rate of hypoglycemia) even in these frail, very old
      inpatients.

PMID- 23160501
TI  - Analysis of suicide in the elderly in Italy. Risk factors and prevention of
      suicidal behavior.
AB  - The authors describe the nationwide scale of suicides among the elderly in Italy
      for the period 1993-2010. The data are derived from the Italian Institute for
      Statistics (ISTAT) and the World Health Organization (WHO). The elderly turned
      out to represent the highest risk category for suicide, with risk increasing with
      age (suicide rates, per 100,000, in men aged 75 or over and aged 65-74 were
      respectively 28.3 and 15.7 in 2007). The rates for men were three times higher
      than those for women. The north-east and north-west regions of Italy had the
      highest rates of suicide in the elderly. Education was inversely related to the
      risk of suicide. Hanging was the most frequent method of suicide in men, and
      precipitation in women. The reasons for suicide, as inferred from available data,
      were predominantly mental-physical illnesses. The risk factors emerging from our
      analysis are discussed from the preventive point of view, in relation to the
      Italian situation and a review of the literature.

PMID- 23160502
TI  - Amputation rate and mortality in elderly patients with critical limb ischemia not
      suitable for revascularization.
AB  - In spite of recent progress in revascularization and anesthesiology procedures,
      in vascular centers today there are still patients with Critical Limb Ischemia
      (CLI) who are not considered suitable for revascularization. Most of these
      patients are elderly, with high co-morbidity factors, poor run off arterial limb
      vessels, and often with a salvageable limb. They are absent or neglected in the
      literature, and generally go untreated. We report details of 24- month
      amputations and mortality rates in 90 patients with CLI who were not considered
      suitable for revascularization, treated from 2005 to 2008 in a dedicated unit of
      our department. Patients with endstage general conditions or needing immediate
      primary amputation were excluded from our study. All patients received
      multidisciplinary assessment. Their median age was 78.4 years; 28 patients
      (31.1%) had rest pain only, and 62 (68.8%) had ischemic skin foot-leg wounds or
      gangrene <2 cm. Sixteen patients (37.7%) were assessed as not suitable for
      revascularization because of poor functional status, and 76 (64.4%) because of
      inadequate outflow limb vessels. Drugs to manage pain were administered to all
      patients (100%), prostanoid infusions were given to 80 (88%), anti-platelet drugs
      to 87 (96%), low molecular weight heparin or oral anticoagulants to 13 (14%),
      spinal cord stimulation to 3 (3%), hyperbaric oxygen treatment to 16 (17%) and
      wound treatment to 62 (68.8%). Toe or other foot-sparing amputations had a rate
      of 13%. After 24 months, the major amputation rate was 9.3% and the mortality
      rate 23.2%. Our observations show that, in spite of progress in revascularization
      procedures, there are still patients with CLI who are not considered suitable for
      revascularization and who could benefit from non-surgical treatment if a tailored
      approach is used.

PMID- 23160504
TI  - The importance of sexual health in the elderly: breaking down barriers and
      taboos.
AB  - Aging-related physical changes do not necessarily lead to a decline in sexual
      functioning: good physical and mental health, a positive attitude toward sex in
      later life, and access to a healthy partner are associated with continued sexual
      activity, and regular sexual expression is associated with good physical and
      mental health. However, it is usually assumed that older adults do not have
      sexual desires, and elderly people often find it difficult to discuss this topic
      with their doctor. There are many potential barriers concerning sexuality in
      older age: the lack of a healthy sexual partner, depression, the monotony of a
      repetitive sexual relationship, a spouse's physical unattractiveness, hormone
      variability, and illness and/or iatrogenic factors. Adaptive coping strategies
      can considerably mitigate the impact of such factors, however, and one way of
      contributing to breaking down barriers and taboos is undoubtedly to ensure that
      physicians are willing to discuss their patients' sexual history. The aim of this
      review was to explore the barriers and taboos to sexual expression in seniors, to
      propose strategies to foster this aspect of their lives, and to help physicians
      investigate the sexual history of their elderly patients.

PMID- 23160503
TI  - Role of bioelectrical impedance analysis in follow-up of hospitalized elderly
      patients with congestive heart failure.
AB  - BACKGROUND AND AIMS: Congestive heart failure (CHF) is characterized by high
      levels of B-type natriuretic peptide (BNP), expanded total body water (TBW) and
      extracellular water (ECW). Bioelectrical impedance analysis (BIA) has
      demonstrated high diagnostic accuracy in CHF but no information is available for
      older patients. We hypothesized that, in the follow-up of patients with CHF, body
      fluid changes estimated by BIA are related to BNP variations rather than with
      body weight. The aim of this study was to evaluate the relationship between
      variations in body fluid compartments, body weight and BNP in hospitalized
      elderly patients with decompensated CHF. METHODS: 49 elderly patients admitted to
      the Geriatric Department for decompensated CHF were included in the study. On
      admission and at discharge, all patients underwent clinical and functional
      assessment and BNP dosage. TBW and ECW were also determined by the BIA method.
      RESULTS: At discharge, all patients showed reductions in TBW (DeltaTBW -2.9 +/-
      3.0 liters), ECW (DeltaECW 1.9 +/- 2.1 liters) and BNP levels (DeltaBNP -219.6 +/
      458.1 pg/mL). Variations in TBW and ECW were correlated with BNP changes (r=0.65
      and 0.62, respectively) rather than with body weight variations and BNP changes
      (r=0.51). CONCLUSIONS: The stronger relationship between fluid variations
      determined by BIA and BNP changes may make BIA a useful method in the follow-up
      of decompensated CHF elderly patients.

PMID- 23160505
TI  - Discussing end-of-life care issues with terminally ill patients and their
      relatives: comparisons among physicians, nurses and psychologists.
AB  - BACKGROUND AND AIMS: The aim of this study was to analyse the end-of-life topics
      most frequently discussed by Italian physicians, nurses and psychologists with
      terminally ill patients and their relatives. Findings were compared with the
      levels of communication reported by physicians in other countries involved in the
      EURELD research project, in Europe and elsewhere. METHODS: An ad hoc
      questionnaire was prepared to measure levels of communication and administered to
      716 professionals (181 physicians, 454 nurses and 81 psychologists) employed in
      geriatric hospital wards, hospices and nursing homes, or registered with
      professional associations in the Veneto and Trentino Alto-Adige regions of north
      east Italy. Statistical analyses (frequency analysis, multivariate logistic
      regression) were conducted on data from questionnaires returned by standard mail
      or email. RESULTS: Communication levels vary for the various end-of-life issues
      which physicians, nurses and psychologists are required to discuss and the
      individuals with whom they deal. Italian physicians are more communicative with
      relatives than with patients, whereas psychologists tend to discuss these
      problems more with patients than with members of their families. Nurses behave in
      much the same way with both patients and relatives. By comparison with their
      colleagues elsewhere in Europe, Italian physicians reveal more evident
      differences in their willingness to discuss end-of-life issues, depending on
      whether they are communicating with patients or relatives. Having received bio
      ethical training helps physicians communicate with their patients. CONCLUSIONS:
      Communicating is a fundamental part of providing care for terminally ill patients
      and support for their families. The patient care process involves several kinds
      of professionals, who are all increasingly called upon to be prepared to discuss
      the end of a patient's life, and to develop a therapeutic relationship which
      includes communicating without evading any of the aspects (and problems) relating
      to this crucial final stage of an individual's life.

PMID- 23160506
TI  - Clinical correlation of mesenteric vascular disease in older patients.
AB  - Mesenteric vascular obstruction is difficult to characterize, since it may
      produce differing acute or chronic clinical pictures and various organic
      symptoms, such as ischemic colitis and abdominal angina. The diagnosis of chronic
      mesenteric ischemia (CMI) is thus still mainly based on historic diagnostic
      criteria drawn up before non-invasive radiological imaging of the mesenteric
      vessels became widespread, and before the current demographic developments
      leading to a rise in the number of older patients with multiple pathologies. With
      this premise, we studied the clinical condition of 85 patients aged over 65 years
      of age, submitted to angio-CT scan for reasons other than neoplastic and general
      pathologies which may cause alterations in mesenteric blood flow, and without the
      typical symptoms of acute intestinal ischemia. Of these, 34 patients presented
      occlusion of at least one mesenteric vessel and 13 were affected by multivessel
      injury. Compared with controls, patients with mesenteric artery disease had lower
      BMI (24.9+/-3.3 vs 26.8+/-4.5) and longer hospital stays (14 vs 6 days), and were
      more frequently affected by vasculopathies in other districts (97.1% vs 80.4%),
      but the only bowel symptom present was diarrhea (21.2% vs 5.9%). These patients
      also took more benzodiazepines and acetylsalicylic acid. The results of stepwise
      logistic analysis of length of hospital stay, vasculopathies, diarrhea, and use
      of benzodiazepines yielded a predictive model with an AUC (area under the curve)
      of 0.81. Our data show that some features characterizing CMI in the geriatric
      population differ from those of the general population.

PMID- 23160507
TI  - Statins and the elderly: recent evidence and current indications.
AB  - Cardiovascular disease (CVD) is estimated to remain as the main cause of death in
      developed nations over the next 30 years, with increased prevalence in the older
      population. This is because the observed decline in the incidence of CVD owing to
      improvements in prevention has now been counterbalanced by the increased shift
      toward an older and thus more fragile population. Statin treatment reduces
      cardiovascular morbidity and mortality in middle-aged adults. However, few
      studies have included older individuals, particularly those aged 80 years or
      over. The adverse effects associated with high doses of statins and their
      interactions with other drugs may give rise to more problems in the elderly
      population. Evidence remains limited regarding the overall benefit of starting
      statin therapy in adults aged 80 and over; so that clinical judgment remains
      necessary in making the decision to use them. In this review, we present
      available evidence from randomized clinical trials, as well as relative community
      and post-approval data directly applicable to the management of CVD in the
      elderly, in both primary and secondary prevention. Also discussed is the latest
      evidence regarding the putative protective effects of statins on senile dementia
      and the relationship between statin treatment and cancer.

PMID- 23160508
TI  - A new diagnosis of myelodysplastic syndrome in hemochromatosis in an elderly man.
AB  - Hemochromatosis is associated with increased risk of hematological neoplasias,
      but studies showing hemochromatosis gene mutations in myelodysplastic syndrome
      (MDS) are scanty, particularly in the elderly. The onset of MDS in
      hemochromatosis usually occurs between 60 and 70 years of age, while cases with
      advanced age are very rare. We report a case of a 78- year-old man with
      hemochromatosis who developed refractory anemia with excess of blasts. Our case
      suggests that in the elderly with hemochromatosis, myelodysplasia should be
      considered a possible cause of anemia.

PMID- 23160509
TI  - The ICRP's lung cancer risk from protracted exposure to radon and its progeny.

PMID- 23160510
TI  - Kidney disease progression and screening cost-effectiveness among African
      Americans.

PMID- 23160511
TI  - Donor-specific antibodies adversely affect kidney allograft outcomes.
AB  - The effect of low titers of donor-specific antibodies (DSAs) detected only by
      sensitive solid-phase assays (SPAs) on renal transplant outcomes is unclear. We
      report the results of a systematic review and meta-analysis of rejection rates
      and graft outcomes for renal transplant recipients with such preformed DSAs,
      defined by positive results on SPA but negative complement-dependent cytotoxicity
      and flow cytometry crossmatch results. Our search identified seven retrospective
      cohort studies comprising a total of 1119 patients, including 145 with isolated
      DSA-SPA. Together, these studies suggest that the presence of DSA-SPA, despite a
      negative flow cytometry crossmatch result, nearly doubles the risk for antibody
      mediated rejection (relative risk [RR], 1.98; 95% confidence interval [CI], 1.36
      2.89; P<0.001) and increases the risk for graft failure by 76% (RR, 1.76; 95% CI,
      1.13-2.74; P=0.01). These results suggest that donor selection should consider
      the presence of antibodies in the recipient, identified by the SPA, even in the
      presence of a negative flow cytometry crossmatch result.

PMID- 23160512
TI  - HNF1beta is essential for nephron segmentation during nephrogenesis.
AB  - Nephrons comprise a blood filter and an epithelial tubule that is subdivided into
      proximal and distal segments, but what directs this patterning during kidney
      organogenesis is not well understood. Using zebrafish, we found that the HNF1beta
      paralogues hnf1ba and hnf1bb, which encode homeodomain transcription factors, are
      essential for normal segmentation of nephrons. Embryos deficient in hnf1ba and
      hnf1bb did not express proximal and distal segment markers, yet still developed
      an epithelial tubule. Initiating hnf1ba/b expression required Pax2a and Pax8, but
      hnf1ba/b-deficient embryos did not exhibit the expected downregulation of pax2a
      and pax8 at later stages of development, suggesting complex regulatory loops
      involving these molecules. Embryos deficient in hnf1ba/b also did not express the
      irx3b transcription factor, which is responsible for differentiation of the first
      distal tubule segment. Reciprocally, embryos deficient in irx3b exhibited
      downregulation of hnf1ba/b transcripts in the distal early segment, suggesting a
      segment-specific regulatory circuit. Deficiency of hnf1ba/b also led to ectopic
      expansion of podocytes into the proximal tubule domain. Epistasis experiments
      showed that the formation of podocytes required wt1a, which encodes the Wilms'
      tumor suppressor-1 transcription factor, and rbpj, which encodes a mediator of
      canonical Notch signaling, downstream or parallel to hnf1ba/b. Taken together,
      these results suggest that Hnf1beta factors are essential for normal segmentation
      of nephrons during kidney organogenesis.

PMID- 23160513
TI  - MicroRNA-494 reduces ATF3 expression and promotes AKI.
AB  - MicroRNA-494 mediates apoptosis and necrosis in several types of cells, but its
      renal target and potential role in AKI are unknown. Here, we found that microRNA
      494 binds to the 3'UTR of activating transcription factor 3 (ATF3) and decreases
      its transcription. In mice, overexpression of microRNA-494 significantly
      attenuated the level of ATF3 and induced inflammatory mediators, such as IL-6,
      monocyte chemotactic protein-1, and P-selectin, after renal ischemia/reperfusion,
      exacerbating apoptosis and further decreasing renal function. Activation of NF
      kappaB mediated this proinflammatory response. In this ischemia/reperfusion
      model, urinary levels of microRNA-494 increased significantly before the rise in
      serum creatinine. In humans, urinary microRNA-494 levels were 60-fold higher in
      patients with AKI than normal controls. In conclusion, upregulation of microRNA
      494 contributes to inflammatory or adhesion molecule-induced kidney injury after
      ischemia/reperfusion by inhibiting expression of ATF3. Furthermore, microRNA-494
      may be a specific and noninvasive biomarker for AKI.

PMID- 23160514
TI  - Is there a role for PGE2 in urinary concentration?
AB  - Prostanoids are prominent, yet complex, components in the maintenance of body
      water homeostasis. Recent functional and molecular studies have revealed that the
      local lipid mediator PGE2 is involved both in water excretion and absorption. The
      biologic actions of PGE2 are exerted through four different G-protein-coupled
      receptors; designated EP1-4, which couple to separate intracellular signaling
      pathways. Here, we discuss new developments in our understanding of the actions
      of PGE2 that have been uncovered utilizing receptor specific agonists and
      antagonists, EP receptor and PG synthase knockout mice, polyuric animal models,
      and the new understanding of the molecular regulation of collecting duct water
      permeability. The role of PGE2 in urinary concentration comprises a variety of
      mechanisms, which are not fully understood and likely depend on which receptor is
      activated under a particular physiologic condition. EP3 and microsomal PG
      synthase type 1 play a role in decreasing collecting duct water permeability and
      increasing water excretion, whereas EP2 and EP4 can bypass vasopressin signaling
      and increase water reabsorption through two different intracellular signaling
      pathways. PGE2 has an intricate role in urinary concentration, and we now suggest
      how targeting specific prostanoid receptor signaling pathways could be exploited
      for the treatment of disorders in water balance.

PMID- 23160517
TI  - Noninvasive image derived heart input function for CMRglc measurements in small
      animal slow infusion FDG PET studies.
AB  - Absolute quantitation of the cerebral metabolic rate for glucose (CMRglc) can be
      obtained in positron emission tomography (PET) studies when serial measurements
      of the arterial [(18)F]-fluoro-deoxyglucose (FDG) input are available. Since this
      is not always practical in PET studies of rodents, there has been considerable
      interest in defining an image-derived input function (IDIF) by placing a volume
      of interest (VOI) within the left ventricle of the heart. However, spill-in
      arising from trapping of FDG in the myocardium often leads to progressive
      contamination of the IDIF, which propagates to underestimation of the magnitude
      of CMRglc. We therefore developed a novel, non-invasive method for correcting the
      IDIF without scaling to a blood sample. To this end, we first obtained serial
      arterial samples and dynamic FDG-PET data of the head and heart in a group of
      eight anaesthetized rats. We fitted a bi-exponential function to the serial
      measurements of the IDIF, and then used the linear graphical Gjedde-Patlak method
      to describe the accumulation in myocardium. We next estimated the magnitude of
      myocardial spill-in reaching the left ventricle VOI by assuming a Gaussian point
      spread function, and corrected the measured IDIF for this estimated spill-in.
      Finally, we calculated parametric maps of CMRglc using the corrected IDIF, and
      for the sake of comparison, relative to serial blood sampling from the femoral
      artery. The uncorrected IDIF resulted in 20% underestimation of the magnitude of
      CMRglc relative to the gold standard arterial input method. However, there was no
      bias with the corrected IDIF, which was robust to the variable extent of
      myocardial tracer uptake, such that there was a very high correlation between
      individual CMRglc measurements using the corrected IDIF with gold-standard
      arterial input results. Based on simulation, we furthermore find that
      electrocardiogram-gating, i.e. ECG-gating is not necessary for IDIF quantitation
      using our approach.

PMID- 23160515
TI  - Deleting the TGF-beta receptor attenuates acute proximal tubule injury.
AB  - TGF-beta is a profibrotic growth factor in CKD, but its role in modulating the
      kidney's response to AKI is not well understood. The proximal tubule epithelial
      cell, which is the main cellular target of AKI, expresses high levels of both TGF
      beta and its receptors. To determine how TGF-beta signaling in this tubular
      segment affects the response to AKI, we selectively deleted the TGF-beta type II
      receptor in the proximal tubules of mice. This deletion attenuated renal
      impairment and reduced tubular apoptosis in mercuric chloride-induced injury. In
      vitro, deficiency of the TGF-beta type II receptor protected proximal tubule
      epithelial cells from hydrogen peroxide-induced apoptosis, which was mediated in
      part by Smad-dependent signaling. Taken together, these results suggest that TGF
      beta signaling in the proximal tubule has a detrimental effect on the response to
      AKI as a result of its proapoptotic effects.

PMID- 23160519
TI  - What's new in Shock? December 2012.

PMID- 23160520
TI  - Combination therapy with molecular hydrogen and hyperoxia in a murine model of
      polymicrobial sepsis.
AB  - Sepsis is the most common cause of death in intensive care units. Some studies
      have found that hyperoxia may be beneficial to sepsis. However, the clinical use
      of hyperoxia is hindered by concerns that it could exacerbate organ injury by
      increasing free radical formation. Recently, it has been suggested that molecular
      hydrogen (H2) at low concentration can exert a therapeutic antioxidant activity
      and effectively protect against sepsis by reducing oxidative stress. Therefore,
      we hypothesized that combination therapy with H2 and hyperoxia might afford more
      potent therapeutic strategies for sepsis. In the present study, we found that
      inhalation of H2 (2%) or hyperoxia (98%) alone improved the 14-day survival rate
      of septic mice with moderate cecal ligation and puncture (CLP) from 40% to 80% or
      70%, respectively. However, combination therapy with H2 and hyperoxia could
      increase the 14-day survival rate of moderate CLP mice to 100% and improve the 7
      day survival rate of severe CLP mice from 0% to 70%. Moreover, moderate CLP mice
      showed significant organ damage characterized by the increases in lung
      myeloperoxidase activity, lung wet-to-dry weight ratio, protein concentration in
      bronchoalveolar lavage, serum biochemical parameters (alanine aminotransferase,
      aspartate aminotransferase, creatinine, and blood urea nitrogen), and organ
      histopathological scores (lung, liver, and kidney), as well as the decrease in
      PaO2/FIO2 ratio at 24 h, which was attenuated by either H2 or hyperoxia alone.
      However, combination therapy with H2 and hyperoxia had a more beneficial effect
      against lung, liver, and kidney damage of moderate or severe CLP mice.
      Furthermore, we found that the beneficial effect of this combination therapy was
      associated with the decreased levels of oxidative product (8-iso-prostaglandin
      F2alpha), increased activities of antioxidant enzymes (superoxide dismutase and
      catalase) and anti-inflammatory cytokine (interleukin 10), and reduced levels of
      proinflammatory cytokines (high-mobility group box 1 and tumor necrosis factor
      alpha) in serum and tissues. Therefore, combination therapy with H2 and hyperoxia
      provides enhanced therapeutic efficacy via both antioxidant and anti-inflammatory
      mechanisms and might be potentially a clinically feasible approach for sepsis.

PMID- 23160522
TI  - Modeling traumatic-hemorrhagic shock--nothing is simple and easy.

PMID- 23160523
TI  - The future of therapeutic myocardial angiogenesis:  retraction.

PMID- 23160521
TI  - gamma-tocopherol nebulization decreases oxidative stress, arginase activity, and
      collagen deposition after burn and smoke inhalation in the ovine model.
AB  - More than 20,000 burn injury victims suffer from smoke inhalation injury in the
      United States annually. In an ovine model of acute lung injury, gamma-tocopherol
      had a beneficial effect when nebulized into the airway. We hypothesize that gamma
      tocopherol scavenges reactive oxygen species (ROS) and reactive nitrogen species
      resulting from burn and smoke inhalation injury and that these ROS/reactive
      nitrogen species activate the arginase pathway, leading to increased collagen
      deposition and decreased pulmonary function. To test this hypothesis, ewes were
      operatively prepared for chronic study, then they were randomly divided into
      groups (n = 8): uninjured, injured, or injured with nebulization (gamma
      tocopherol [950 mg/g] and alpha-tocopherol [40 mg/g] from hours 3 to 48 after the
      injury). The injury, under deep anesthesia, consisted of a 20% total body surface
      burn and 36 breaths of cotton smoke; all animals were killed after 3 weeks.
      Treatment increased lung gamma-tocopherol at 3 weeks after gamma-tocopherol
      nebulization compared with injured sheep (1.75 +/- 0.62 nmol/g vs. 0.45 +/- 0.06,
      P < 0.05). The expression of dimethylarginine dimethylaminohydrolase-2, which
      degrades asymmetrical dimethylarginine, a nitric oxide synthase inhibitor,
      significantly increases with gamma-tocopherol treatment compared with injured
      sheep (P < 0.05). Arginase activity (0.15 +/- 0.02 MUM urea/MUg protein vs. 0.24
      +/- 0.009, P < 0.05), ornithine aminotransferase (11,720 +/- 888 vs. 13,170 +/-
      1,775), and collagen deposition (0.62 +/- 0.12 MUM hydroxyproline/MUg protein vs.
      1.02 +/- 0.13, P < 0.05) significantly decrease with gamma-tocopherol compared
      with injured animals without gamma-tocopherol. The decreases in arginase and
      collagen with gamma-tocopherol are associated with significantly increased
      diffusion capacity (P < 0.05) and decreased lung wet-to-dry ratio (P < 0.05).
      Smoke-induced chronic pulmonary dysfunction is mediated through the
      ROS/asymmetrical dimethylarginine/arginase pathway, and ROS scavengers such as
      gamma-tocopherol may be a potential therapeutic management of burn patients with
      inhalation injury.

PMID- 23160525
TI  - Childhood misfortune and adult health: enduring and cascadic effects on somatic
      and psychological symptoms?
AB  - OBJECTIVE: This article traces the influence of early misfortune on somatic and
      psychological symptoms, examining whether the health disadvantages endure and/or
      worsen over a decade. METHOD: The study uses two waves of data from the Midlife
      Development in the United States study. Structural equation models are used to
      assess change in somatic and psychological symptoms. RESULTS: Findings reveal
      that childhood abuse is associated with more initial somatic and psychological
      symptoms among American adults, but that family structure and financial strain
      had little association with baseline adult symptoms. The effects of abuse were
      not observed at Wave 2 (W2), net of Wave 1 (W1) symptoms. DISCUSSION: The results
      suggest an enduring-but not cascadic-effect of childhood abuse on adult health.
      There was little evidence that the consequences of early misfortune waned over
      the course of time or were less substantial for older adults; but neither did
      these early life experiences contribute to worsened symptoms over a decade of
      observation.

PMID- 23160527
TI  - Liver-specific disruption of the murine glucagon receptor produces alpha-cell
      hyperplasia: evidence for a circulating alpha-cell growth factor.
AB  - Glucagon is a critical regulator of glucose homeostasis; however, mechanisms
      regulating glucagon action and alpha-cell function and number are incompletely
      understood. To elucidate the role of the hepatic glucagon receptor (Gcgr) in
      glucagon action, we generated mice with hepatocyte-specific deletion of the
      glucagon receptor. Gcgr(Hep)(-/-) mice exhibited reductions in fasting blood
      glucose and improvements in insulin sensitivity and glucose tolerance compared
      with wild-type controls, similar in magnitude to changes observed in Gcgr(-/-)
      mice. Despite preservation of islet Gcgr signaling, Gcgr(Hep)(-/-) mice developed
      hyperglucagonemia and alpha-cell hyperplasia. To investigate mechanisms by which
      signaling through the Gcgr regulates alpha-cell mass, wild-type islets were
      transplanted into Gcgr(-/-) or Gcgr(Hep)(-/-) mice. Wild-type islets beneath the
      renal capsule of Gcgr(-/-) or Gcgr(Hep)(-/-) mice exhibited an increased rate of
      alpha-cell proliferation and expansion of alpha-cell area, consistent with
      changes exhibited by endogenous alpha-cells in Gcgr(-/-) and Gcgr(Hep)(-/-)
      pancreata. These results suggest that a circulating factor generated after
      disruption of hepatic Gcgr signaling can increase alpha-cell proliferation
      independent of direct pancreatic input. Identification of novel factors
      regulating alpha-cell proliferation and mass may facilitate the generation and
      expansion of alpha-cells for transdifferentiation into beta-cells and the
      treatment of diabetes.

PMID- 23160528
TI  - Local autoantigen expression as essential gatekeeper of memory T-cell recruitment
      to islet grafts in diabetic hosts.
AB  - It is generally believed that inflammatory cues can attract noncognate,
      "bystander" T-cell specificities to sites of inflammation. We have shown that
      recruitment of naive and in vitro activated autoreactive CD8+ T cells into
      endogenous islets requires local autoantigen expression. Here, we demonstrate
      that absence of an autoantigen in syngeneic extrapancreatic islet grafts in
      diabetic hosts renders the grafts "invisible" to cognate memory (and naive) T
      cells. We monitored the recruitment of islet-specific glucose-6-phosphatase
      catalytic subunit-related protein (IGRP)206-214-reactive CD8+ T cells into
      IGRP206-214-competent and IGRP206-214-deficient islet grafts in diabetic wild
      type or IGRP206-214(-/-) nonobese diabetic hosts (harboring either naive and
      memory T cells or only naive IGRP206-214-specific T-cells, respectively). All
      four host-donor combinations had development of recurrent diabetes within 2
      weeks. Wild-type hosts recruited IGRP206-214-specific T cells into IGRP206
      214(+/+) but not IGRP206-214(-/-) grafts. In IGRP206-214(-/-) hosts, there was no
      recruitment of IGRP206-214-specific T cells, regardless of donor type. Graft
      derived IGRP206-214 activated naive IGRP206-214-specific T cells, but graft
      destruction invariably predated their recruitment. These results indicate that
      recurrent diabetes is exclusively driven by autoreactive T cells primed during
      the primary autoimmune response, and demonstrate that local antigen expression is
      a sine qua non requirement for accumulation of memory T cells into islet grafts.
      These findings underscore the importance of tackling autoreactive T-cell memory
      after beta-cell replacement therapy.

PMID- 23160530
TI  - Gliotransmission and brain glucose sensing: critical role of endozepines.
AB  - Hypothalamic glucose sensing is involved in the control of feeding behavior and
      peripheral glucose homeostasis, and glial cells are suggested to play an
      important role in this process. Diazepam-binding inhibitor (DBI) and its
      processing product the octadecaneuropeptide (ODN), collectively named
      endozepines, are secreted by astroglia, and ODN is a potent anorexigenic factor.
      Therefore, we investigated the involvement of endozepines in brain glucose
      sensing. First, we showed that intracerebroventricular administration of glucose
      in rats increases DBI expression in hypothalamic glial-like tanycytes. We then
      demonstrated that glucose stimulates endozepine secretion from hypothalamic
      explants. Feeding experiments indicate that the anorexigenic effect of central
      administration of glucose was blunted by coinjection of an ODN antagonist.
      Conversely, the hyperphagic response elicited by central glucoprivation was
      suppressed by an ODN agonist. The anorexigenic effects of centrally injected
      glucose or ODN agonist were suppressed by blockade of the melanocortin-3/4
      receptors, suggesting that glucose sensing involves endozepinergic control of the
      melanocortin pathway. Finally, we found that brain endozepines modulate blood
      glucose levels, suggesting their involvement in a feedback loop controlling whole
      body glucose homeostasis. Collectively, these data indicate that endozepines are
      a critical relay in brain glucose sensing and potentially new targets in
      treatment of metabolic disorders.

PMID- 23160531
TI  - Pathogenesis of A-beta+ ketosis-prone diabetes.
AB  - A-beta+ ketosis-prone diabetes (KPD) is an emerging syndrome of obesity,
      unprovoked ketoacidosis, reversible beta-cell dysfunction, and near-normoglycemic
      remission. We combined metabolomics with targeted kinetic measurements to
      investigate its pathophysiology. Fasting plasma fatty acids, acylcarnitines, and
      amino acids were quantified in 20 KPD patients compared with 19 nondiabetic
      control subjects. Unique signatures in KPD--higher glutamate but lower glutamine
      and citrulline concentrations, increased beta-hydroxybutyryl-carnitine, decreased
      isovaleryl-carnitine (a leucine catabolite), and decreased tricarboxylic acid
      (TCA) cycle intermediates--generated hypotheses that were tested through stable
      isotope/mass spectrometry protocols in nine new-onset, stable KPD patients
      compared with seven nondiabetic control subjects. Free fatty acid flux and acetyl
      CoA flux and oxidation were similar, but KPD had slower acetyl CoA conversion to
      beta-hydroxybutyrate; higher fasting beta-hydroxybutyrate concentration; slower
      beta-hydroxybutyrate oxidation; faster leucine oxidative decarboxylation;
      accelerated glutamine conversion to glutamate without increase in glutamate
      carbon oxidation; and slower citrulline flux, with diminished glutamine amide
      nitrogen transfer to citrulline. The confluence of metabolomic and kinetic data
      indicate a distinctive pathogenic sequence: impaired ketone oxidation and fatty
      acid utilization for energy, leading to accelerated leucine catabolism and
      transamination of alpha-ketoglutarate to glutamate, with impaired TCA anaplerosis
      of glutamate carbon. They highlight a novel process of defective energy
      production and ketosis in A-beta+ KPD.

PMID- 23160533
TI  - Theoretical aspects of dynamic nuclear polarization in the solid state--spin
      temperature and thermal mixing.
AB  - Dynamic nuclear polarization is a method which allows for a dramatic increase of
      the NMR signals due to polarization transfer between electrons and their
      neighboring nuclei, via microwave irradiation. These experiments have become
      popular in recent years due to the ability to create hyper-polarized chemically
      and biologically relevant molecules, in frozen glass forming mixtures containing
      free radicals. Three mechanisms have been proposed for the polarization transfer
      between electrons and their surrounding nuclei in such non-conducting samples:
      the solid effect and cross effect mechanisms, which are based on quantum
      mechanics and relaxation on small spin systems, and thermal mixing, which
      originates from the thermodynamic macroscopic notion of spin temperature. We have
      recently introduced a spin model, which is based on the density matrix formalism
      and includes relaxation, and applied it to study the solid effect and cross
      effect mechanisms on small spin systems. In this publication we use the same
      model to describe the thermal mixing mechanism, and the creation of spin
      temperature. This is obtained without relying on the spin temperature formalism.
      Simulations of small model systems are used on systems with homogeneously and
      inhomogeneously broadened EPR lines. For the case of a homogeneously broadened
      line we show that the nuclear enhancement results from the thermal mixing and
      solid effect mechanisms, and that spin temperatures are created in the system. In
      the inhomogeneous case the enhancements are attributed to the solid effect and
      cross effect mechanisms, but not thermal mixing.

PMID- 23160532
TI  - Early metabolic markers of the development of dysglycemia and type 2 diabetes and
      their physiological significance.
AB  - Metabolomic screening of fasting plasma from nondiabetic subjects identified
      alpha-hydroxybutyrate (alpha-HB) and linoleoyl-glycerophosphocholine (L-GPC) as
      joint markers of insulin resistance (IR) and glucose intolerance. To test the
      predictivity of alpha-HB and L-GPC for incident dysglycemia, alpha-HB and L-GPC
      measurements were obtained in two observational cohorts, comprising 1,261
      nondiabetic participants from the Relationship between Insulin Sensitivity and
      Cardiovascular Disease (RISC) study and 2,580 from the Botnia Prospective Study,
      with 3-year and 9.5-year follow-up data, respectively. In both cohorts, alpha-HB
      was a positive correlate and L-GPC a negative correlate of insulin sensitivity,
      with alpha-HB reciprocally related to indices of beta-cell function derived from
      the oral glucose tolerance test (OGTT). In follow-up, alpha-HB was a positive
      predictor (adjusted odds ratios 1.25 [95% CI 1.00-1.60] and 1.26 [1.07-1.48],
      respectively, for each standard deviation of predictor), and L-GPC was a negative
      predictor (0.64 [0.48-0.85] and 0.67 [0.54-0.84]) of dysglycemia (RISC) or type 2
      diabetes (Botnia), independent of familial diabetes, sex, age, BMI, and fasting
      glucose. Corresponding areas under the receiver operating characteristic curve
      were 0.791 (RISC) and 0.783 (Botnia), similar in accuracy when substituting alpha
      HB and L-GPC with 2-h OGTT glucose concentrations. When their activity was
      examined, alpha-HB inhibited and L-GPC stimulated glucose-induced insulin release
      in INS-1e cells. alpha-HB and L-GPC are independent predictors of worsening
      glucose tolerance, physiologically consistent with a joint signature of IR and
      beta-cell dysfunction.

PMID- 23160529
TI  - HLA-A*24 is an independent predictor of 5-year progression to diabetes in
      autoantibody-positive first-degree relatives of type 1 diabetic patients.
AB  - We investigated whether HLA-A*24 typing complements screening for HLA-DQ and for
      antibodies (Abs) against insulin, GAD, IA-2 (IA-2A), and zinc transporter-8
      (ZnT8A) for prediction of rapid progression to type 1 diabetes (T1D).
      Persistently Ab(+) siblings/offspring (n = 288; aged 0-39 years) of T1D patients
      were genotyped for HLA-DQA1-DQB1 and HLA-A*24 and monitored for development of
      diabetes within 5 years of first Ab(+). HLA-A*24 (P = 0.009), HLA-DQ2/DQ8 (P =
      0.001), and positivity for IA-2A +/- ZnT8A (P < 0.001) were associated with
      development of T1D in multivariate analysis. The 5-year risk increased with the
      number of the above three markers present (n = 0: 6%; n = 1: 18%; n = 2: 46%; n =
      3: 100%). Positivity for one or more markers identified a subgroup of 171 (59%)
      containing 88% of rapid progressors. The combined presence of HLA-A*24 and IA
      2A(+) +/- ZnT8A(+) defined a subgroup of 18 (6%) with an 82% diabetes risk. Among
      IA-2A(+) +/- ZnT8A(+) relatives, identification of HLA-A*24 carriers in addition
      to HLA-DQ2/DQ8 carriers increased screening sensitivity for relatives at high Ab-
      and HLA-inferred risk (64% progression; P = 0.002). In conclusion, HLA-A*24
      independently predicts rapid progression to T1D in Ab(+) relatives and
      complements IA-2A, ZnT8A, and HLA-DQ2/DQ8 for identifying participants in
      immunointervention trials.

PMID- 23160536
TI  - uPAR signaling is under par for the podocyte course.

PMID- 23160534
TI  - Functional lesions in dysphagia due to acute stroke: discordance between abnormal
      findings of bedside swallowing assessment and aspiration on videofluorography.
AB  - INTRODUCTION: Bedside swallowing assessments are often used to assess dysphagia.
      However, in some patients, aspiration pneumonia occurs without any problems on
      bedside swallowing assessments and some patients do not suffer aspiration
      pneumonia despite abnormal results of bedside swallowing assessments in acute
      stroke. To detect the differences of lesions related to bedside swallowing
      assessment abnormality and aspiration, we investigated swallowing-related
      functional lesions in terms of cerebral blood flow in patients with dysphagia
      after stroke. METHODS: The study included 50 acute stroke patients who underwent
      bedside swallowing assessments and videofluorography as well as single-photon
      emission computed tomography (CT) at approximately the same time. Bedside
      swallowing assessments included repetitive saliva swallowing test and modified
      water swallowing test as dry and wet swallowing tasks. The presence or absence of
      aspiration was assessed using videofluorography. We divided patients into three
      subgroups based on the outcomes of the bedside swallowing assessments and
      presence or absence of aspiration. Statistical image analysis was performed using
      single-photon emission CT to determine their relationship with bedside swallowing
      assessments and videofluorography results. RESULTS: Twenty-seven (54.0%) and 28
      (56.0%) patients had abnormal repetitive saliva swallowing test and modified
      water swallowing test results. Videofluorography indicated aspiration in 35
      (70.0%) patients. In comparing patients with and without abnormal results on each
      test, the groups with abnormal repetitive saliva swallowing test, abnormal
      modified water swallowing test, and aspiration demonstrated lower cerebral blood
      flow in the left precuneus, left insula, and anterior cingulate gyrus,
      respectively. CONCLUSIONS: Based on the analysis of cerebral blood flow,
      functional lesions differed across abnormal repetitive saliva swallowing test and
      abnormal modified water swallowing test findings and aspiration on
      videofluorography, and each test may assess different functions among the many
      processes involved in swallowing.

PMID- 23160539
TI  - Eye trauma during the 2011 Egyptian revolution.
AB  - BACKGROUND: Cairo university hospitals are at the heart of Cairo with close
      proximity to Tahrir (Liberation) square and had received the vast majority of
      casualties during the Egyptian revolution. The aim of this study was to analyze
      the eye injuries during the uprising. DESIGN: Retrospective cohort study.
      METHODS: Data were obtained from patients' paper records, interview with treating
      ophthalmologists, and whenever possible patients were interviewed and examined.
      An electronic medical template had been specially developed for recording these
      data. Main outcome measures were the flow of patients and their demographics,
      diagnoses, visual acuities pre and post interventions, investigations and
      management. Whenever required results were compared at 95 % confidence interval.
      RESULTS: There were 184 patients (mean age 27.3 +/- 9.6 years) with 195 injured
      eyes of whom 96.7 % were males and 11 patients had both eyes injured. Seventy
      seven percent of patients had been admitted within 24 h of injury. Open globe
      injuries comprised 87 % of the eyes of which 147 eyes received 259 imaging
      investigations. The presenting visual acuities were worse than 3/60 in 72.5 % of
      eyes which were even worse post interventions and that was significantly
      dependent on the presenting vision. Wound repair was the primary intervention in
      85 % of eyes while 50 % of the secondary interventions were vitrectomies.
      CONCLUSIONS: Presenting visual acuity is a valid prognostic factor in the setting
      of mass eye casualty. Management of open globe injuries continues to pose
      difficult challenges especially bilateral ones.

PMID- 23160538
TI  - Enhanced depth imaging of the choroid in patients with neovascular age-related
      macular degeneration treated with anti-VEGF therapy versus untreated patients.
AB  - PURPOSE: To compare the subfoveal choroidal thickness (SFCT) between patients
      with neovascular age-related macular degeneration (nAMD) who had multiple
      intravitreal injections of anti-vascular endothelial growth factor (anti-VEGF)
      agents and those with treatment-naive nAMD. METHODS: This retrospective case
      control study included 15 patients in group 1 (nAMD in one eye which had received
      at least three anti-VEGF injections and early AMD in the fellow eye) and 15
      patients in group 2 (newly diagnosed nAMD in one eye which had not received any
      treatment and early AMD in the fellow eye). They underwent enhanced depth imaging
      optical coherence tomography (OCT), and two OCT readers manually measured the
      SFCT. Inter-ocular difference in SFCT (nAMD eye minus fellow eye) was calculated
      for each patient. RESULTS: The nAMD eyes in group 1 had received a median (range)
      of four (3-8) intravitreal injections of anti-VEGF agents, and the OCT scans were
      performed at a median (range) of 9 (4-17) months after the first injection. The
      median inter-ocular difference in SFCT in groups 1 and 2 were not significantly
      different (13.5 and 3.0 MUm in groups 1 and 2 respectively, p=0.60). There was
      also no statistically significant difference in SFCT between nAMD and fellow eyes
      (p=0.16), although there was a trend for greater median SFCT in the nAMD eyes.
      CONCLUSION: The data from this small cohort suggests that no gross reduction in
      SFCT appears in nAMD patients after a time interval of at least 4 months between
      initiating repeated treatment with anti-VEGF therapy and OCT imaging. However, a
      study with a much larger sample size or longitudinal design is required to detect
      possible small fluctuations in SFCT in nAMD eyes receiving anti-VEGF therapy.

PMID- 23160540
TI  - Putting problem formulation at the forefront of GMO risk analysis.
AB  - When applying risk assessment and the broader process of risk analysis to
      decisions regarding the dissemination of genetically modified organisms (GMOs),
      the process has a tendency to become remarkably complex. Further, as greater
      numbers of countries consider authorising the large-scale dissemination of GMOs,
      and as GMOs with more complex traits reach late stages of development, there has
      been increasing concern about the burden posed by the complexity of risk
      analysis. We present here an improved approach for GMO risk analysis that gives a
      central role to problem formulation. Further, the risk analysis strategy has been
      clarified and simplified in order to make rigorously scientific risk assessment
      and risk analysis more broadly accessible to diverse stakeholder groups.

PMID- 23160541
TI  - Biotech crops: imperative for achieving the millenium development goals and
      sustainability of agriculture in the climate change era.
AB  - Biotechnological intervention in the development of crops has opened new vistas
      in agriculture. Central to the accomplishment of the Millennium Development Goals
      (MDGs), biotech-agriculture is essential in meeting these targets. Biotech crops
      have already made modest contributions toward ensuring food and nutrition
      security by reducing losses and increasing productivity, with less pesticide
      input. These crops could help address some of the major challenges in agriculture
      based economies created by climate change. Projections of global climate change
      expect the concentration of greenhouse gases to increase, aridization of the
      environment to increase, temperature fluctuations to occur sharply and
      frequently, and spatial and temporal distribution of rainfall to be disturbed-all
      of which will increase abiotic stress-related challenges to crops. Countering
      these challenges and to meet the food requirement of the ever-increasing world
      population (expected to reach 9 billion by 2030) we need to (1) develop and use
      biotech crops for mitigating adverse climatic changes; (2) develop biotech crops
      resilient to adverse environmental conditions; and (3) address the issues/non
      issues raised by NGO's and educate the masses about the benefits of biotech
      crops.

PMID- 23160542
TI  - Dermatitis and cellulitis in leopard geckos (Eublepharis macularius) caused by
      the Chrysosporium anamorph of Nannizziopsis vriesii.
AB  - An epizootic of ulcerative to nodular ventral dermatitis was observed in a large
      breeding colony of 8-month to 5-year-old leopard geckos (Eublepharis macularius)
      of both sexes. Two representative mature male geckos were euthanized for
      diagnostic necropsy. The Chrysosporium anamorph of Nannizziopsis vriesii (CANV)
      was isolated from the skin lesions, and identification was confirmed by
      sequencing of the internal transcribed spacer region of the rRNA gene.
      Histopathology revealed multifocal to coalescing dermal and subcutaneous
      heterophilic granulomas that contained septate fungal hyphae. There was also
      multifocal epidermal hyperplasia with hyperkeratosis, and similar hyphae were
      present within the stratum corneum, occasionally with terminal chains of
      arthroconidia consistent with the CANV. In one case, there was focal extension of
      granulomatous inflammation into the underlying masseter muscle. This is the first
      report of dermatitis and cellulitis due to the CANV in leopard geckos.

PMID- 23160543
TI  - Marked depletion of the water-channel protein, AQP5, in the canine nictitating
      membrane glands might contribute to the development of KCS.
AB  - The objectives of this study were to investigate the normal histological
      localization of aquaporin (AQP) 5 protein in the lacrimal and nictitating
      membrane glands and to compare this localization in healthy and
      keratoconjunctivitis sicca (KCS) dogs. Lacrimal and nictitating membrane glands
      of 5 healthy Beagles and nictitating membrane glands of 5 KCS dogs (3 Beagles and
      2 mongrel dogs: 0-13 years) were used for the present study. The owners of the
      KCS dogs did not consent to perform biopsies of the lacrimal glands. The
      localization and distribution of AQP5 protein were investigated by an
      immunohistochemical technique. In immunohistochemical staining, AQP5 was
      localized in the apical site of acinar epithelial and ductal epithelial cells
      from both the lacrimal and nictitating membrane glands in healthy dogs. However,
      AQP5 was not detected in the 5 KCS dogs. These results for immunohistochemical
      AQP5 localization might correlate with the deficiency in tear secretion found in
      KCS dogs.

PMID- 23160544
TI  - A proposed protocol for acceptance and constancy control of computed tomography
      systems: a Nordic Association for Clinical Physics (NACP) work group report.
AB  - BACKGROUND: Quality assurance (QA) of computed tomography (CT) systems is one of
      the routine tasks for medical physicists in the Nordic countries. However,
      standardized QA protocols do not yet exist and the QA methods, as well as the
      applied tolerance levels, vary in scope and extent at different hospitals.
      PURPOSE: To propose a standardized protocol for acceptance and constancy testing
      of CT scanners in the Nordic Region. MATERIAL AND METHODS: Following a Nordic
      Association for Clinical Physics (NACP) initiative, a group of medical
      physicists, with representatives from four Nordic countries, was formed. Based on
      international literature and practical experience within the group, a
      comprehensive standardized test protocol was developed. RESULTS: The proposed
      protocol includes tests related to the mechanical functionality, X-ray tube,
      detector, and image quality for CT scanners. For each test, recommendations
      regarding the purpose, equipment needed, an outline of the test method, the
      measured parameter, tolerance levels, and the testing frequency are stated. In
      addition, a number of optional tests are briefly discussed that may provide
      further information about the CT system. CONCLUSION: Based on international
      references and medical physicists' practical experiences, a comprehensive QA
      protocol for CT systems is proposed, including both acceptance and constancy
      tests. The protocol may serve as a reference for medical physicists in the Nordic
      countries.

PMID- 23160546
TI  - Passing the baton.

PMID- 23160545
TI  - Graphene nanoribbon electrical decoupling from metallic substrates.
AB  - We address the structural and electronic properties of graphene nanoribbons
      (GNRs) covalently immobilized on a metallic substrate by means of an organic
      layer. The GNR-organic layer and organic layer-metal interfaces can be thought of
      as constituents of a nanodevice and have been accurately studied using large
      scale density functional theory calculations. Our results demonstrate the
      possibility of combining nanopatterned metal-organic layer substrates with
      selected GNRs to obtain well ordered and stable structures while preserving the
      GNR energy band gap, an essential requirement for any switching nanodevice.

PMID- 23160547
TI  - Minimally invasive partial fasciectomy for Dupuytren contractures.
AB  - Treatment options for the Dupuytren contractures vary from percutaneous needle
      aponeurotomy, open fasciotomy or fasciectomy, dermofasciectomy, and more
      recently, injectable collagenase. Although utilization of injectable collagenase
      avoids a formal surgical procedure, not all patients are eligible and some
      patients do not feel comfortable with an enzyme injection or the associated
      risks, which may include hematoma, wound dehiscence, or tendon rupture. This
      study describes the technique and early results of partial fasciectomy through a
      mini-incision approach as an additional treatment option for Dupuytren
      contractures. We found that this procedure results in contracture correction with
      a low rate of complications and thus provides the surgeon with an alternative
      treatment option to offer patients.

PMID- 23160548
TI  - Reconstructing the interosseous membrane:  a technique using synthetic graft and
      endobuttons.
AB  - Reconstruction of the interosseous membrane is an emerging procedure designed to
      help restore anatomic and biomechanical relationships within the forearm after a
      longitudinal instability injury. The indication for this reconstruction is proven
      acute or chronic longitudinal instability of the forearm. This technique uses a
      synthetic braided graft tied over endobuttons at radial and ulnar tunnels. It can
      also be combined with other procedures such as radial head replacement, wafer
      procedures, and even ulnar shortening osteotomies for comprehensive management of
      the condition. Early results indicate that this reconstruction can produce
      clinical improvement in some patients. Further follow-up is required to determine
      the long-term durability of the construct, but early results are encouraging in a
      complex patient population.

PMID- 23160549
TI  - Hamate hook nonunion treated with a hook plate:  case report and surgical
      technique.
AB  - Despite of its rarity, hamate hook nonunion can cause several complications like
      tendon rupture or loss of grip strength. Admitted treatments in the literature
      are excision of the bone fragment or its open reduction and internal fixation. We
      report a clinical case of a high-level baseball player with hamate hook nonunion
      treated with an original technique of fixation using a hook plate.

PMID- 23160550
TI  - Replacement with silicone wrist implant after failed silicone wrist arthroplasty:
      3 case reports in inflammatory arthritis.
AB  - Revision surgery after failed silicone wrist arthroplasty is often challenging.
      In particular, in cases of inflammatory arthritis there is a high incidence of
      extensive bone loss which leads to a high complication rate in wrist fusion as a
      salvage procedure. Sometimes the surgeon may be faced with a patient in poor
      overall medical condition, who is very low demand so that the complexities of
      wrist fusion after a failed silicone arthroplasty may be contraindicated. For
      that situation, revision with a silicone prosthesis is a easy method in cases of
      severe osseous destruction in low demand patients with a long history of
      inflammatory arthritis.With 3 case reports will describe the topic of replacement
      with silicone wrist implant after failed silicone wrist arthroplasty.

PMID- 23160551
TI  - The Ioban drape: a simple method to improve finger surgery safety and efficiency.
AB  - Surgery involving the fingers can be technically challenging especially when
      utilizing fluoroscopic imaging. The surgical field is often obscured by the
      remaining fingers and attempts to position the hand may expose the surgeon and
      assistants to additional radiation exposure. This paper describes a simple and
      effective technique to remove the uninvolved fingers from the surgical field
      allowing for a more efficient operative procedure with less radiation exposure.

PMID- 23160552
TI  - Scaphoid excision and 4-corner fusion using retrograde headless compression
      screws.
AB  - Scapholunate advanced collapse is a predictable form of wrist arthritis resulting
      from longstanding scapholunate instability. Four-corner fusion and scaphoid
      excision is a reliable procedure used to treat scapholunate advanced collapse
      wrist that improves pain and preserves range of motion. Multiple methods of
      achieving fixation have been described for the procedure including K-wires,
      staples, and headless compression screws. In previously described techniques, the
      compression screws are inserted in an antegrade manner, breaching the articular
      surface of the lunate. Even small areas of chondral damage may undermine the long
      term durability of the radiocarpal joint. Given the 4-corner fusion relies on the
      integrity of the radiolunate articulation for success, it would seem advantageous
      to preserve the articular cartilage of the lunate. The technique described here
      involves retrograde insertion of headless compression screws to achieve a 4
      corner fusion. Although it is still early, we anticipate that this procedure will
      result in similar fusion rates to other forms of fixation.

PMID- 23160553
TI  - Two-team simultaneous open surgical treatment in bilateral shoulder fracture
      dislocation.
AB  - Different surgical options have been described for the treatment of bilateral
      shoulder fracture dislocations. We report 2 cases of bilateral shoulder fracture
      dislocation treated simultaneously by 2 surgical teams. One case had bilateral
      hemiarthroplasty performed, and the second case had 1 hemiarthroplasty and
      McLaughlin procedure on the other shoulder. A device to allow holding the patient
      in a bend chair position, with both shoulders hanging outside the operative
      table, allowing their free movement, was designed. At 1-year follow-up, neither
      of the patients had complications and both are pleased with their early result.
      Simultaneous treatment of both the shoulders by 2 different surgical teams in
      bilateral shoulder fracture dislocations that need surgical treatment has the
      advantages of reduced overall hospitalization time, reduced anesthetic risk,
      faster return to work, and reduced overall cost of care. The decision for
      simultaneous bilateral shoulder surgery must be made in concert with the patient,
      medical consultant, and anesthesiologist. LEVEL OF EVIDENCE: Level IV-case
      series.

PMID- 23160554
TI  - Arthrodesis of the thumb metacarpophalangeal joint with plate fixation.
AB  - This is a surgical technique for arthrodesis of the thumb metacarpophalangeal
      joint using a low-profile plate. Using the principles of tension band fixation
      and interfragmentary compression, a high rate of fusion is achieved with a low
      incidence of complications. The technique is versatile allowing fixation at any
      desired position. It can be used in porotic bone and avoids the need for
      postoperative immobilization.

PMID- 23160555
TI  - Technical tip:  coverage of the wrist arthroscopy tower using a sterile
      concentrical endoscopy camera drape.
AB  - Wrist arthroscopy allows complete visualization under magnification and is
      essentially a diagnostic and therapeutic tool. The first wrist arthroscopy was
      described by Chen in 1979. Since then, the indications and applications for wrist
      arthroscopy continue to expand as new techniques and instrumentation evolve.

PMID- 23160556
TI  - The simple wire interosseous fixation technique (SWIFT) for reattachment of FDP
      avulsions with a large bony fragment.
AB  - Avulsion injuries of the flexor digitorum profundus tendon can be with or without
      a bony fragment. Types 3, 4, and 5 injuries often have a sizeable bony fragment.
      In the past, they have been repaired with either a screw, plate, or pull-out wire
      with a dorsal button, often in combination with a K wire to immobilize the distal
      interphalangeal joint. We illustrate with 2 cases a simple technique for secure
      repair of the flexor digitorum profundus avulsions with a bony fragment. In
      contrast to previously described techniques, our technique involves minimal
      dissection, has a significantly reduced risk of fracture to the bony fragment, is
      completely internalized thereby reducing the risk of postoperative infection and
      allows immediate mobilization.

PMID- 23160557
TI  - Repair of the acutely unstable elbow:  use of tensionable anchors.
AB  - Acute ruptures of the medial or lateral collateral ligaments of the elbow
      associated with elbow dislocations have traditionally been repaired back to their
      respective epicondyles using suture anchors or transosseous sutures. Tensioning
      of those ligaments using conventional techniques had been difficult because of
      the need to maintain tension while tying and securing sequential knots.
      Tensionable anchors are a new generation of anchors that have been used for
      rotator cuff repair, but can be employed for the repair of collateral ligaments
      and capsular tears. It allows fine control and sequential tensioning of the
      ligament repair, and on-table assessment of stability before locking the anchor.
      We present a modified surgical technique for the repair of collateral ligaments
      repair using tensionable anchors in acute elbow dislocations or fracture
      dislocations.

PMID- 23160558
TI  - Salvage reconstruction of failed interposition arthroplasty at the base of the
      thumb.
AB  - We present an operative procedure designed to revise a failed arthroplasty at the
      base of the thumb. This report describes a reliable operation that corrects
      residual instability and malignment which results in thumbs that are weak and
      painful despite a previous procedure. The operation has also been used as a
      primary procedure for arthritis of the trapeziometacarpal joint where instability
      and subluxation was a major component of the problem requiring joint
      reconstruction. The unique features of this procedure include a reinforced double
      thickness tendon graft, a unique tendon anchor, and a fascia lata allograft
      spacer. Significant functional improvement is anticipated when joint
      reconstruction provides increased proximal stability. Pinch and grip measurements
      improve. Pain scores also diminish after the operation. Hand function and patient
      satisfaction can be substantially improved with revision arthroplasty when the
      initial operation has failed to provide a thumb that is mobile, stable, and pain
      free. The technical features of the procedure address reduction of malignment,
      restoring of anatomic balance, and secure fixation of the proximal apex of the
      thumb metacarpal which restores thumb reduction position and digital balance.

PMID- 23160559
TI  - Four-corner arthrodesis with a locking, dorsal circular polyether-ether-ketone
      (PEEK-Optima) plate.
AB  - Scaphoidectomy and 4-corner arthrodesis can be a successful salvage procedure for
      scaphoid nonunion advanced collapse and scapholunate advanced collapse.
      Traditional methods of fixation include Kirschner wires, staples, and/or headless
      compression screws. Nonlocking, dorsal circular plates, manufactured from
      stainless steel, have been advocated to allow early wrist range of motion and
      improved union rates. However, the reported union rates have been variable and
      inconsistent. This wide results have been attributed to the difficulty in
      assessing union with plain film radiograph due to the radio-opaque plate.
      Recently, a locking, dorsal circular plate, comprised of a radiolucent polyether
      ether-ketone (PEEK-Optima), has been introduced with the additional benefit of
      providing a fixed-angle construct and allowing a more accurate assessment of bone
      union with plain film imaging studies.

PMID- 23160560
TI  - Radial shortening osteotomy in advanced stages of Kienbock disease.
AB  - Radial shortening osteotomy is a well-accepted treatment for Kienbock disease in
      stages I to IIIA. The usefulness of this procedure in more advanced stages of the
      disease is controversial. In this study, 27 cases of stage IIIB and IV of
      Kienbock disease underwent radial shortening osteotomy and were followed for a
      mean period of 54.9 months (9 to 117 mo). Twenty-four patients had stage IIIB and
      3 patients had stage IV disease. Sixteen of the affected wrists were on the
      dominant side. All patients were evaluated clinically and radiologically at last
      follow-up. Modified Mayo Score was used for clinical evaluation. The measured
      radiologic parameters included carpal height ratio, Stahl index, and
      radioscaphoid angle. In stage IIIB, 41.6% of cases had good, 54.2 had fair, and
      4.2 had poor result, whereas in stage IV all patients showed poor result. The
      mean range of flexion-extension was 84.4% of the unaffected side. Considering the
      percentage of preserved motion, this procedure seems to be a good alternative to
      partial fusion for stage IIIB when the patient is willing to preserve more
      degrees of motion. Although the number of patients with stage IV disease was
      limited in this study, poor result in all of them may show the uselessness of
      this procedure in stage IV.

PMID- 23160561
TI  - Sequestrectomy in primary osteomyelitis of the humerus:  a new indication for
      posterior approach.
AB  - Surgical treatment for primary osteomyelitis of the humerus is not well
      standardized; guidelines come from the scientific literature on osteomyelitis of
      the femur and tibia. Commonly deltopectoral approach is used for the proximal
      humerus and posterior approach for the distal humerus. Sequestrectomy alone or
      the use of antibiotic cement (bead pouch technique) is advised in case of chronic
      osteomyelitis. Berger and Buckwalter described a posterior approach to the
      proximal part of the humerus for an excisional biopsy of an osteoid-osteoma. We
      found that this approach is also useful for sequestrectomy in primary
      osteomyelitis of the humerus. We describe the technique and make a review of the
      literature.

PMID- 23160562
TI  - A new era of clinical dopamine transporter imaging using 123I-FP-CIT.
AB  - (123)I-labeled 2beta-carbomethoxy-3beta-(4-iodophenyl)-N-(3
      fluoropropyl)nortropane ((123)I-FP-CIT) was approved for clinical use in 2011 by
      the Food and Drug Administration. (123)I-FP-CIT is a radioligand for brain
      dopamine transporter (DAT) imaging that is useful for the differential diagnosis
      of Parkinson disease (PD) and other diseases that mimic PD. The sensitivity and
      specificity of (123)I-FP-CIT SPECT for PD diagnosis are more than 90% and
      equivalent to those of other DAT SPECT methods. In the near future, the clinical
      indications of DAT imaging are expected to be broadened; for example, including
      treatment response assessment, disease progression monitoring, and early
      diagnosis of premotor PD in each individual patient.

PMID- 23160563
TI  - A combined NMR/DFT study on the ion pair structure of [(PR1(2)R2)Au(eta2-3
      hexyne)]BF4 complexes.
AB  - The interionic structure of four gold(i) pi-alkyne ion pairs, with general
      formula [(PR(1)(2)R(2))Au(eta(2)-3-hexyne)]BF(4) (R(1) = R(2) = (t)Bu, 1a; R(1) =
      (t)Bu, R(2) = o-diphenyl, 2a; R(1) = R(2) = 2,4,6-trimethoxyphenyl, 3a; R(1) =
      R(2) = 2,4-di-tert-butylphenoxy, 4a), was studied by (19)F, (1)H-HOESY NMR
      spectroscopy. In all the cases the anion locates mainly close to the alkyne, but
      the degree of specificity of location strongly depends on the P-ligand and it is
      high for ion pairs bearing poorly electron donating PR(1)(2)R(2) ligands
      (particularly, ) and low for ion pairs with strongly electron donating
      PR(1)(2)R(2) ones (such as 3a). This result is rationalized through relativistic
      DFT calculations, showing that the electronic properties of the P-ligand finely
      tune the charge accumulation on the alkyne and, consequently, its ability of
      attracting the anion.

PMID- 23160566
TI  - Supramolecular chemical biology; bioactive synthetic self-assemblies.
AB  - The regulation of recognition events in nature via dynamic and reversible self
      assembly of building blocks has inspired the emergence of supramolecular
      architectures with similar biological activity. Synthetic molecules of diverse
      geometries self-assemble in water to target biological systems for applications
      ranging from imaging and diagnostics, through to drug delivery and tissue
      engineering. Many of these applications require the ability of the supramolecular
      system to actively recognize specific cell surface receptors. This molecular
      recognition is typically achieved with ligands, such as small molecules,
      peptides, and proteins, which are introduced either prior to or post self
      assembly. Advantages of the non-covalent organization of ligands include the
      responsive nature of the self-assembled structures, the ease of supramolecular
      synthesis and the possibility to incorporate a multiple array of different
      ligands through pre-mixing of the building blocks. This review aims to highlight
      the diversity of self-assembled nanostructures constructed from mono-disperse
      synthetic building blocks; with a particular focus on their design, self
      assembly, functionalization with bioactive ligands and effects thereof on the
      self-assembly, and possible applications.

PMID- 23160567
TI  - Structural and molecular diversification of the Anguimorpha lizard mandibular
      venom gland system in the arboreal species Abronia graminea.
AB  - In the past, toxinological research on reptiles has focused principally on
      clinically important species. As a result, our understanding of the evolution of
      the reptile venom system is limited. Here, for the first time, we describe the
      structural and molecular evolutionary features of the mandibular toxin-secreting
      gland of Abronia graminea, a representative of one of the poorly known and
      entirely arboreal lineages of anguimorph lizards. We show that the mandibular
      gland is robust and serous, characters consistent with those expected of a toxin
      secreting gland in active use. A wide array of transcripts were recovered that
      were homologous to those encoded by the indisputably venomous helodermatid
      lizards. We show that some of these toxin transcripts are evolving under active
      selection and show evidence of rapid diversification. Helokinestatin peptides in
      particular are revealed to have accumulated residues that have undergone episodic
      diversifying selections. Conversely, the natriuretic peptides have evolved under
      tremendous evolutionary constraints despite being encoded in tandem with
      helokinestatins by the same gene precursor. Of particular note is the sequencing
      for the first time of kunitz peptides from a lizard toxin-secreting gland. Not
      only are kunitz peptides shown to be an ancestral toxicoferan toxin, the
      ancestral state of this peptide is revealed to be a dual domain encoding
      precursor. This research provides insight into the evolutionary history of the
      ancient toxicoferan reptile venom system. In addition, it shows that even
      'clinically irrelevant' species can be a rich source of novel venom components,
      worthy of investigation for drug design and biomedical research.

PMID- 23160568
TI  - Flow cytometry enables a high-throughput homogeneous fluorescent antibody-binding
      assay for cytotoxic T cell lytic granule exocytosis.
AB  - We developed a homogeneous phenotypic fluorescence end-point assay for cytotoxic
      T lymphocyte lytic granule exocytosis. This flow cytometric assay measures
      binding of an antibody to a luminal epitope of a lysosomal membrane protein (LAMP
      1) that is exposed by exocytosis to the extracellular solution. Washing to remove
      unbound antibody is not required. Confirming the assay's ability to detect novel
      active compounds, we screened at a concentration of 50 uM a synthetic diversity
      library of 91 compounds in a 96-well plate format, identifying 17 compounds that
      blocked by 90% or more. The actions of six structurally related tetracyano
      hexahydroisoindole compounds that inhibited by ~90% at a concentration of 10 uM
      were investigated further. Four reduced elevations in intracellular Ca(2+); it is
      likely that depolarization of the cells' membrane potential underlies the effect
      for at least two of the compounds. Another compound was found to be a potent
      inhibitor of the activation of the mitogen-activated protein (MAP) kinase ERK.
      Finally, we transferred the assay to a 384-well format and screened the Prestwick
      Compound Library using high-throughput flow cytometry. Our results indicate that
      our assay will likely be a useful means of screening libraries for novel
      compounds with important biological activities.

PMID- 23160569
TI  - [Recent studies on intracranial stenosis].
AB  - CLINICAL ISSUE: Symptomatic intracranial stenoses are associated with a high risk
      of stroke. Medical management with platelet inhibitors or anticoagulation has not
      been shown to substantially lower this risk. Hence, alternative treatment options
      are desperately needed. TREATMENT INNOVATIONS: The concept of percutaneous
      intervention using balloon angioplasty with or without stenting is appealing at
      first sight which is why intracranial balloons and stents were developed.
      PERFORMANCE: Initial studies using dedicated intracranial stents were more
      promising; however, the only randomized trial recently published using a
      dedicated intracranial self-expanding stent demonstrated a high periprocedural
      complication rate. EVALUATION AND PRACTICAL RECOMMENDATIONS: Due to study design
      limitations it would be premature to categorically denounce an interventional
      option for the treatment of symptomatic intracranial stenoses. More importantly,
      the results of the randomized SAMMPRIS trial should stimulate the development of
      safer technology and patient selection to minimize procedural risks. This will
      perhaps allow significant risk reduction of this potentially devastating
      intracranial condition when it cannot otherwise be addressed.

PMID- 23160570
TI  - [Cardiac magnetic resonance tomography in the diagnostics of restrictive and
      unclassified cardiopathies].
AB  - CLINICAL/METHODICAL ISSUE: Besides ischemic heart disease cardiomyopathies are
      common causes of heart failure and sudden cardiac death. STANDARD RADIOLOGICAL
      METHODS: The diagnostic spectrum in cardiomyopathies comprises non-invasive and
      invasive examination techniques. METHODICAL INNOVATIONS: The exact verification
      of certain cardiomyopathies necessitates knowledge of the latest classification
      of cardiomyopathies as well as dedicated examination protocols. PERFORMANCE:
      Modern imaging modalities, such as echocardiography and cardiac magnetic
      resonance imaging (MRI) have emerged as useful imaging tools in the investigation
      of patients suspected of having many different types of cardiomyopathies.
      ACHIEVEMENTS: Based on a better understanding of the underlying pathophysiology
      several diagnostic criteria have been defined using cardiac MRI. In particular
      there is an increasing importance of cardiac MRI in the description of patients
      with restrictive and unclassified cardiomyopathies. PRACTICAL RECOMMENDATIONS:
      Echocardiography still remains the modality of choice in the diagnostics of
      unclear left ventricular heart failure. Further diagnostic work-up should include
      cardiac MRI in case of any lack of clarity.

PMID- 23160571
TI  - The Journal of the Norwegian Medical Association on iPad--doctors are changing
      their reading habits.

PMID- 23160572
TI  - Individualised treatment of metastatic cancer.

PMID- 23160573
TI  - [Our language].

PMID- 23160575
TI  - [What should be presented to the regional ethics committee?].

PMID- 23160578
TI  - [Bad results without radiologist].

PMID- 23160581
TI  - [Circumcision only for medical reasons].

PMID- 23160582
TI  - [Weakened privacy with e-prescription].

PMID- 23160583
TI  - Many sphincter injuries are preventable.

PMID- 23160584
TI  - [Which projects should be submitted to the regional ethics committee?].

PMID- 23160585
TI  - [Is too much research being done in this country?].

PMID- 23160587
TI  - Therapeutic drug monitoring (TDM) repertoire in Norway.
AB  - BACKGROUND: In many clinical situations it is useful to measure drug levels in
      patient samples. The purpose of this survey is to obtain an overview of the
      therapeutic drug monitoring analyses offered by Norwegian laboratories. MATERIAL
      AND METHOD: At the end of 2011, the authors of this article phoned all the public
      and private hospitals in Norway, and located their laboratories. All clinical
      chemical and pharmacological laboratories were contacted and asked to state which
      drug analyses (including drugs-of-abuse and toxic alcohols, but excluding
      metabolites) they performed in blood/serum at the time in question. The overview
      thus obtained was updated and quality assured by means of further telephone
      contact with the laboratories in August 2012. RESULTS: Around 80 laboratories
      were contacted. In August 2012, 49 of them performed analyses of drugs in
      blood/serum. Altogether, these laboratories offered 151 different analyses. This
      article provides an overview of the analyses that were carried out, and where.
      INTERPRETATION: The overview of analyses provided here can be used as a tool in
      everyday practice. However, the user must be aware that the analytical repertoire
      of the laboratories is constantly changing. A web-based, dynamic version is
      currently being planned.

PMID- 23160588
TI  - Primary care doctors' management of low back pain patients--ten years after.
AB  - BACKGROUND: In 2001, we undertook a survey among general practitioners in Aust
      Agder county to describe how patients with spinal problems were examined and
      treated by GPs. We have now conducted a new survey among the regular GPs in the
      same county. MATERIAL AND METHOD: All regular GPs in Aust-Agder county received
      an invitation to participate in the study. The doctors were asked to continuously
      register over two weeks all patients who visited the doctor and gave spinal
      problems as their main reason, and to describe all measures that were implemented
      after the consultation. RESULTS: Of the 87 practising regular GPs, 53% responded.
      In total, the doctors had received 5,822 patients during the period of study,
      whereof 3% had reported spinal problems. The examination and treatment provided
      to these patients were on the whole unchanged since 2001. Only 41% of the doctors
      reported to cooperate regularly with a physiotherapist, and 11% with a
      chiropractor, a reduction from 73% and 35% respectively in 2001. The doctors
      reported co-morbidity in 37% of the patients. Patients were referred for
      diagnostic imaging with equal frequency as in 2001, although skeletal x-ray and
      CT had mainly been replaced by MRI. INTERPRETATION: The doctors in this sample
      treat patients with spinal problems in approximately the same way as the doctors
      in the 2001 survey, but cooperate less frequently with physiotherapists and
      chiropractors, and MRI has become the primary alternative when diagnostic imaging
      is requisitioned.

PMID- 23160589
TI  - Angioedema--assessment and treatment.
AB  - BACKGROUND: Angioedema has numerous hereditary, acquired and iatrogenic causes. A
      number of studies show that angioedema is inadequately assessed and treated
      during its acute phase as well as in the follow-up period. We present an
      algorithm for the assessment and treatment of patients with angioedema. KNOWLEDGE
      BASE: The article is based on a literature search in PubMed, a review of
      bibliographies and the authors' clinical experience and research. RESULTS: The
      majority of angioedema patients have accompanying urticaria.
      Pathophysiologically, angioedemas are divided into histaminergic and non
      histaminergic forms. In a large group of patients no positive trigger is
      identified. On assessment in hospital the most frequently identified cause is
      drug intake, normally angiotensin-converting-enzyme inhibitors and NSAIDs , while
      allergic/pseudoallergic and idiopathic reactions are more commonly seen in
      general practice. There are a number of rare causes of angioedema, all of which
      are important to keep in mind. The acute and prophylactic treatment will depend
      on the subtype of angioedema and is best provided through cross-disciplinary
      collaboration. INTERPRETATION: Angioedema is a potentially life-threatening
      condition and should be assessed and treated systematically. It is important to
      remember that angioedema is either histaminergic or non-histaminergic, as the
      treatment of the two types is different.

PMID- 23160590
TI  - Neuroprotective treatment for perinatal asphyxia.
AB  - BACKGROUND: Perinatal asphyxia can cause serious illness or death. By taking
      steps in the "latent phase", which occurs 6-24 hours after the hypoxic event, the
      neurological damage caused by perinatal asphyxia can be limited. We wish to
      present a selection of such measures that are either established treatment today
      or that appear promising. METHOD: We searched in the Medline and Cochrane Library
      databases for options for treating perinatal asphyxia. RESULTS: An overwhelming
      number of potential treatments were identified. From among them we selected 44
      indexed, peer-reviewed original articles in English on strategies for
      neuroprotective treatment after perinatal asphyxia. The treatments target
      different cellular mechanisms that cause neurological damage following perinatal
      asphyxia. In randomised clinical trials, only hypothermia treatment has improved
      the long-term outcome for newborns with perinatal asphyxia. Xenon gas,
      erythropoeitin and allopurinol are undergoing clinical testing. INTERPRETATION:
      The efficacy of xenon gas, erythropoeitin and allopurinol in combination with the
      established treatment form of hypothermia must be studied more closely.
      Antioxidants, stem cell treatment and DNA repair mechanisms can pave the way for
      new opportunities in the future.

PMID- 23160591
TI  - [Bloated stomach without gas].

PMID- 23160592
TI  - [A woman in her thirties with pain in her fingers and toes].
AB  - Hand pain is a relatively common complaint, and careful anamnesis and clinical
      examination may reveal its aetiology. Multiple joint involvement suggests either
      osteoarthritis or inflammatory arthritis. In the returning traveller, a more
      exotic explanation might be the case. A 31 year old woman was referred to our
      outpatient clinic for evaluation due to peripheral joint arthralgia. The symptoms
      started six months earlier, on the same day she returned from a three-week
      holiday in India. There were no signs of inflammatory arthritis or
      osteoarthritis. Blood tests were normal. Chikungunya virus serology was positive.
      The patient received symptomatic treatment with nonsteroid anti-inflammatory
      drugs and improved over a period of months. We describe the first case of
      Chikungunya fever diagnosed in our hospital.

PMID- 23160593
TI  - Viruses out travelling.

PMID- 23160594
TI  - [Genome sequencing for personalized cancer treatment].

PMID- 23160595
TI  - [Physicians and alternative treatment].

PMID- 23160596
TI  - [General Condition--what is it?].

PMID- 23160599
TI  - Effects of ghrelin on the intracellular calcium concentration in rat aorta
      vascular smooth muscle cells.
AB  - BACKGROUND/AIMS: Ghrelin has been regarded as a cardioprotective factor with
      complicated mechanisms. Whether ghrelin is vasodilative or vasoconstrictive in
      nature is controversial, and the effects of ghrelin on intracellular calcium
      concentration are still unclear. To explore the mechanisms involved in the
      vasoactive regulation of ghrelin at the cellular level, we investigated the
      effects of ghrelin on calcium concentrations in rat aorta vascular smooth muscle
      cells (VSMCs). METHODS: We obtained VSMCs via cell culture and stained the cells
      with Furo-2 AM. Western blotting was used to verify growth hormone secretagogue
      receptor (GHS-R1a) expression in VSMCs. The intracellular calcium variations
      affected by ghrelin and the interactions of ghrelin with angiotensin II (AngII),
      Sq22536, and potassium chloride (KCl) were observed using a calcium imaging and
      analysis system. RESULTS: Western blotting revealed good GHS-R1a expression in
      VSMCs. The most prominent finding in the present study was that ghrelin inhibited
      the AngII-induced increase in the calcium concentration. This inhibition was
      reversed by the adenylate cyclase inhibitor Sq22536 and the GHS-R1a antagonist (D
      Lys(3))- GHRP-6. This finding revealed the potential vasodilative effects of
      ghrelin at the cellular level. We did not observe any effects of ghrelin on
      intracellular calcium concentrations in resting VSMCs or the increase of calcium
      concentration induced by KCl. CONCLUSION: Ghrelin inhibited the increase in the
      intracellular calcium concentration of rat aorta VSMCs induced by AngII, which
      may depend on the activation of the cAMP/PKA pathway.

PMID- 23160601
TI  - Kikuchi-Fujimoto disease: a case supporting a role for human herpesvirus 7
      involvement in the pathogenesis.
AB  - Kikuchi's disease, also known as histiocytic necrotizing lymphadenitis, is a
      rare, benign, and self-limited disorder of unknown cause that is usually
      characterized by cervical lymphadenopathy and fever. The etiology and
      pathogenesis remain unknown, but the clinical presentation, course, and
      histologic changes suggest an immune response of T cells and histiocytes to an
      infectious agent. Numerous inciting agents have been proposed. However, the
      association between human herpesvirus 7 and Kikuchi's disease has been rarely
      reported as a possible etiologic agent of Kikuchi's disease. We report the case
      of a 24-year-old Caucasian female patient with cervical lymphadenopathy and
      isolated pruriginous maculo-papular lesions who was diagnosed of Kikuchi's
      disease in whom the presence of human herpesvirus 7 DNA was documented in the
      affected lymph node specimen in the absent of other viruses. Therefore, a
      possible etiologic relation between the Kikuchi's disease of this patient and
      human herpesvirus 7 was established, supporting a role for human herpesvirus 7
      involvement in the pathogenesis.

PMID- 23160602
TI  - Structure and magnetism of a mixed-valence octanuclear manganese(II/III) cluster
      derived from carbamoylcyanonitrosomethanide (ccnm).
AB  - A mixed-valence octanuclear manganese complex of formula
      [Mn(II)(4)Mn(III)(4)O(4)(ccnm)(12)].4MeCN.7H(2)O (1.4MeCN.7H(2)O) (ccnm =
      carbamoylcyanonitrosomethanide) has been synthesized and characterized by single
      crystal X-ray diffraction, IR spectroscopy, elemental analysis and magnetic
      measurements. The metal core of 1 adopts a tetra-capped (with Mn(II) ions)
      distorted [Mn(III)(4)O(4)](4+) cubane topology, with a three-J magnetic analysis
      indicating that the cluster displays dominant antiferromagnetic interactions.
      Three equally possible fits were obtained, all leading to a spin ground state of
      S = 0 with S = 1, 2 and 3 close in energy. Comparisons of the magnetic analysis
      are made with that published for a related Mn(8) cluster and, more generally,
      with other Mn(III)Mn(III) and Mn(III)Mn(II) fragments in clusters of various
      types.

PMID- 23160604
TI  - Radiographic examination of the greater sciatic notch in determining the sex
      among Iranian people.
AB  - The distinctive morphology of the human innominate bone (os coxae) and its clear
      sexual dimorphism make it of interest from anatomical, anthropological and
      forensic points of view. The features of the greater sciatic notch of the coxae
      are characteristic and are commonly used to determine sex in unknown individuals.
      In this study, several measurements of the greater sciatic notch, e.g. width
      (AB), depth (OC) and width of the posterior segment (OB) were taken and indices I
      and II were calculated in 64 adult (32 men and 32 women) and side (right: left)
      coxae radiography (A-P view). Results indicated that out of all the parameters
      studied, width of the notch (right and left) (P < 0.001), posterior segment width
      (right and left) (P < 0.001), right (P = 0.036) and left (P = 0.008) index II of
      notch were found to be significantly greater in women as compared with men.
      Discriminant function analysis showed that the accuracy of sex determination
      varied from 100% in the men and 40% in the women groups to 70% for the total
      group. These results can be used as an aid to the identification of human
      skeletal remains in Iranian people. 

PMID- 23160605
TI  - [Phytotherapy of benign prostate syndrome and prostate cancer: better than
      placebo].
AB  - In some countries plant extracts have belonged to the most popular drugs for the
      treatment of the benign prostatic syndrome (BPS) for decades; however, only few
      of the large number of published studies meet the criteria of the WHO benign
      prostatic hyperplasia (BPH) consensus conference. The few placebo-controlled long
      term (study period >6 months) studies suggest a positive effect of some extracts
      (saw palmetto fruit, beta-sitosterol, urtica, rye grass and a saw palmetto/urtica
      combination) on lower urinary tract symptoms (LUTS), urinary flow rate, post-void
      residual volume but effects on prostate volume or prostate-specific antigen (PSA)
      were only inconsistently demonstrable. To date no study has proven an effect on
      disease progression, such as acute urinary retention or need for surgical
      interventions. Due to the controversial data various extraction techniques and
      compositions of various products, neither American, European, British nor German
      BPH guidelines recommend plant extracts for the indication BPS although some
      placebo-controlled trials provided encouraging data. Further prospective studies
      according to WHO standards are required to determine the role of plant extracts
      for the management of BPS. For the indication of prostate cancer (PCa) plant
      extracts have been evaluated for disease prevention and management of several
      tumor stages but none of these studies have provided convincing evidence that
      plant extracts are superior to placebo and none of the Pica guidelines have
      recommended their use.Based on current knowledge plant extracts can never
      supplement evidence-based PCa management and should be used only in addition to
      the standard treatment. There is no scientific evidence for the use of dietary
      supplementation with high doses of vitamins or selenium-containing products.

PMID- 23160606
TI  - [Magnetic resonance urography in pediatric urology].
AB  - Magnetic resonance urography (MRU) provides high resolution imaging of the
      urogenital system and the use of paramagnetic contrast agents enables a
      functional depiction. This review summarizes existing data concerning this
      diagnostic procedure in pediatric urology. A systematic search and assessment of
      the literature was performed.A total of 12 studies were reviewed in detail. In
      mostly small study populations a great heterogeneity concerning methodology, use
      of comparative examinations and standards of reference was noted. Besides the
      quality of anatomical imaging, the functional study of renal excretory function
      and differential renal function was also assessed. Only a few studies performed
      statistical analyses.The authors' rating of MRU was mostly positive. Due to
      methodical weaknesses, lack of independent standards of reference and statistical
      analyses the overall level of evidence was low. Further high quality studies will
      be necessary to assess the value of MRU for the diagnostic workup in pediatric
      urology.

PMID- 23160607
TI  - [Transforming growth factor beta in prostate cancer: cellular effects and basic
      molecular mechanisms].
AB  - The multifunctional cytokine transforming growth factor beta (TGFbeta) plays a
      dual role in prostate cancer (PCa), cell growth and tumorigenesis, reflected by
      its opposing properties of anti-oncogenic (e.g. growth inhibition and apoptosis)
      and pro-oncogenic effects (e.g. proliferation, cell motility and remodelling of
      the microenvironment). In the later stages of PCa, TGFbeta loses anti
      proliferative and thereby tumor-suppressive functions and shifts to a tumorigenic
      phenotype, mainly initiated by cross-talk between TGFbeta signalling and other
      proliferation signal transduction pathways, such as mitogen-activated protein
      kinase (MAPK) and androgen receptor (AR) signalling. Although TGFbeta plays an
      important role in tumor progression little is known about the underlying effects
      of TGFbeta in the molecular pathology of PCa.

PMID- 23160608
TI  - [Unconventional treatment procedures of the bladder in paraplegia and
      myelomeningocele].
AB  - The established treatment of neurogenic lower urinary tract dysfunction (NLUTD)
      in patients with spinal cord injury (SCI) or meningomyelocele (MMC) is mainly
      conservative and is aimed at the lower urinary tract. For example, oral
      antimuscarinic medication is the standard treatment of neurogenic detrusor
      overactivity. Recently, however, treatment aiming directly or indirectly at the
      innervation of the urinary tract has gained increasing attention. Current
      evidence does not justify the use of nerve rerouting but the existing preliminary
      data are more promising for MMC patients than for those with SCI. Sacral
      neuromodulation is already a therapeutic option for incomplete SCI patients.
      Initial data from a pilot study indicate that in patients with complete SCI
      implementation in the spinal shock phase may prevent the development of NLUTD.
      Licensing of onabotulinum toxin A (Botox(r)) facilitated its clinical use for
      treating NLUTD but it is limited to the indication of neurogenic detrusor
      overactivity incontinence with a dosage of 200 IU. The mentioned unconventional
      treatments, although discussed controversially, are promising future treatment
      options for NLUTD.

PMID- 23160609
TI  - [Pathophysiology and therapy of castration-resistant prostate cancer].
AB  - Advanced prostate cancer that progresses under androgen deprivation therapy has
      long been thought to be refractory to further hormonal treatment. The
      identification of the mechanism of cancer cells has revolutionized this
      understanding. Today it is known that castration-resistant prostate cancer (CRPC)
      still receives signals through the androgen receptor transduction pathways and
      furthermore is sensitive to hormone therapy. New substances, such as abiraterone,
      enzalutamide (MDV3100) and TAK 700 target these mechanisms of resistance of
      cancer cells, stop testosterone production and show not only better tolerance but
      also effective antitumor activity. Due to the heterogeneity of tumors with cells
      in varying states of differentiation, the treatment of CRPC with androgen
      deprivation therapy remains a cornerstone of disease management. To what extent
      the experimental findings and the recommendations in the guidelines are put into
      practice was the subject of a survey among urologists analyzing their treatment
      strategies with CRPC patients.

PMID- 23160610
TI  - [The results of the European randomized study of screening for prostate cancer
      (ERSPC) 2012: confirmation or disappointment?].

PMID- 23160611
TI  - A milestone for mental health in South Africa.

PMID- 23160612
TI  - Board of international affairs, Pan-African division, quarterly newsletter,
      African international division, royal college of psychiatrists.

PMID- 23160613
TI  - Mental health services in South Africa: taking stock.
AB  - There is new policy commitment to mental health in South Africa, demonstrated in
      the national mental health summit of April 2012. This provides an opportunity to
      take stock of our mental health services. At primary care level key challenges
      include- training and supervision of staff in the detection and management of
      common mental disorders, and the development of community-based psychosocial
      rehabilitation programmes for people with severe mental illness (in collaboration
      with existing non-governmental organizations). At secondary level, resources need
      to be invested in 72-hour observation facilities at designated district and
      regional hospitals, in keeping with the Mental Health Care Act. At tertiary
      level, greater continuity of care with primary and secondary levels is required
      to prevent "revolving door" patterns of care. There are major challenges and also
      opportunities related to the high level of comorbidity between mental illness and
      a range of other public health priorities, notably HIV/AIDS, cardiovascular
      disease and diabetes. The agenda for mental health services research needs to
      shift to a focus on evaluating interventions. With current policy commitment, the
      time to act and invest in evidence-based mental health services is now.

PMID- 23160614
TI  - The Mental Health Care Act No 17 - South Africa. Trials and triumphs: 2002-2012.
AB  - The Mental Health Care Act 17 of 2002 (MHCA) was promulgated in 2004. It has been
      hailed as one of the most progressive pieces of mental health legislation. A true
      measure of its merit is the degree to which it has transformed mental health
      services and in particular improved the quality of care. This paper will describe
      the impact of the Act on mental health care service delivery in the country.
      Literature pertaining to the MHCA published from 2006-2012, a report compiled by
      the South African Society of Psychiatrists and the results of a national survey
      conducted among Heads of Departments of Psychiatry, Mental Health Review Boards
      and Provincial Directors of Mental Health was reviewed. The MHCA has been
      successful in shifting the emphasis of care from psychiatric institutions to
      general hospitals. However, the integration of services has been hampered by
      infrastructure constraints and shortages of mental health personnel. It has been
      less successful in integrating mental health care into primary health services
      where the focus remains largely on the pharmacological maintenance treatment of
      the chronically mentally ill. Little attention has been given to the health
      promotion, disease prevention and rehabilitation aspects of care. Mental health
      review boards contend with limited resources, administrative challenges and
      limited political support. Isolated pockets of success characterised the
      implementation of the MHCA across the country. Greater investment of resources is
      needed to ensure the comprehensive implementation of the Act.

PMID- 23160615
TI  - Developing the philosophy of recovery in South African mental health services.
AB  - The recovery movement has emerged as an important and powerful force in the
      design and implementation of mental health care in many countries around the
      world. This involves new and more positive understandings of the concept of
      recovery, both as an individual outcome and as a goal of services. The basis for
      these understandings is examined, with particular emphasis on long-term outcomes
      in schizophrenia, and a brief history of the origins of the recovery movement is
      given. An argument is made for the implementation of a recovery framework within
      South African mental health services.

PMID- 23160616
TI  - Integrating mental health into general health care: lessons from HIV.
AB  - Mental disorders are highly prevalent across all health settings. Where they are
      co-morbid with other chronic physical disorders, a complex bidirectional
      relationship exists between them. While mental disorders may result in an
      increase in adverse healthrelated outcomes, they are amenable to cost-effective
      treatments. In resource-limited settings, many barriers to the detection and
      treatment of mental disorders exist. One approach to the effective targeting of
      the available resources is to utilize a "risk-flag" approach, wherein individuals
      at-risk of treatment failure are identified and routed into more intensive mental
      health screening and intervention. This paper discusses how lessons from HIV
      services may inform how to improve mental health care and integration in HIV
      settings, as well as in other chronic diseases.

PMID- 23160618
TI  - Psychiatry and mental health research in South Africa: national priorities in a
      low and middle income context.
AB  - The recent National Mental Health Summit included discussion of research
      priorities for South Africa. This paper reviews some of the background literature
      that is relevant to this key issue. It draws attention to one contested question,
      the extent to which research in low and middle income countries should address
      questions about fundamental mechanisms and clinical treatments versus focusing on
      questions about implementation and systems research? In addressing this question,
      the paper argues that the boundary between good clinical practice and good
      academic scholarship is not nearly as distinct as is often assumed (the "research
      fallacy"); prospective rigorous assessments, retrospective clinical audits,
      evidence-based medicine, and useful information systems all point to the mutual
      interdependence of good practice and good scholarship. Finally, some general
      conclusions that the majority of summit delegates participating in the discussion
      on research agreed to, are presented.

PMID- 23160617
TI  - Addressing psychosocial problems among persons living with HIV.
AB  - The large number of persons living with HIV in Southern Africa has implications
      for mental health services for this population. Data have emerged in recent years
      showing that a substantial number of persons living with HIV also have mental
      health problems. Yet, the practice of routine screening for psychiatric disorders
      in the context of HIV care is controversial. Moreover, common mental health
      problems, if left undetected and untreated, may have severe consequences for
      adherence to antiretroviral therapy (ART), which in turn will likely lead to
      severe health consequences for patients. There are high costs associated with
      employing professional psychologists, counsellors, and social workers to provide
      psychosocial support to ART users. As a result, in many contexts lay counsellors
      and patient advocates have been employed as a less costly alternative. High
      standards of training of lay counsellors, as well as on-going supervision and
      support to patient advocates is necessary to ensure optimal outcomes/results.

PMID- 23160619
TI  - Research in lower middle income countries - recommendations for a national mental
      health research agenda in South Africa.
AB  - In the current mental health environment in South Africa, the development of a
      relevant mental health research agenda poses several challenges. This paper
      provides a brief overview of the current state of published research in mental
      health and, using a translation research framework, makes recommendations for
      five strategic directions to be considered in the development of a national
      mental health research agenda.

PMID- 23160620
TI  - Suicide prevention: a proposed national strategy for South Africa.
AB  - Suicidal behaviour is an important public health problem globally and in Africa.
      A brief overview of the nature and severity of the problem is provided, but the
      primary aim of this paper is to identify priorities and prevention strategies for
      reducing suicidal behaviour in South Africa by discussing a framework for a
      proposed national prevention programme. South African suicide rates range from
      11.5 per 100 000 to as high as 25 per 100 000 of the population, depending on
      sampling procedures and research methods. About 11% of all non-natural deaths are
      suicide related. On average 9.5% of non-natural deaths in young people are due to
      suicide. It is a complex phenomenon and risk factors are, therefore,
      multifactorial and multidimensional. Some of the most important ones are
      identified and several priorities and prevention possibilities for reducing
      suicidal behaviour are recommended. The outline and structure for such a national
      suicide prevention programme is underpinned by research undertaken locally and
      internationally. It requires a comprehensive multi-sectoral approach that
      involves both health care and non-health care sectors and action at various
      levels utilising a framework based on a set of guiding principles and a range of
      strategies with specific objectives as a national priority within an
      interdisciplinary context.

PMID- 23160621
TI  - Rupture of sinus of Valsalva aneurysm with aorto-biventricular fistulas and right
      ventricular outflow tract obstruction: a unique association.
AB  - Sinus of Valsalva aneurysms are a rare entity. Rupture of such aneurysms is a
      major cause of aortocardiac fistulas usually occurring between the right sinus of
      Valsalva and right cardiac chambers. We report an exceptional case of a ruptured
      congenital sinus of Valsalva aneurysm with fistulas involving both the right- and
      left-ventricular outflow tracts and causing RVOT obstruction. We also demonstrate
      the utility of computed tomography angiography and transesophageal
      echocardiography in diagnosing these fistulas. 

PMID- 23160622
TI  - Pulmonary atresia with restrictive ventricular septal defect: a rare association.

PMID- 23160623
TI  - Quadricuspid aortic valve: multimodality imaging.

PMID- 23160624
TI  - Expression of P2X5 receptors in the rat, cat, mouse and guinea pig dorsal root
      ganglion.
AB  - P2X receptors are ATP-gated cationic channels composed of seven cloned subunits
      (P2X(1 -7)). P2X(3) homomultimer and P2X(2/3) heteromultimer receptors expressed
      by primary afferent dorsal root ganglion (DRG) neurons are involved in pain
      processing. The aim of the study was to investigate the expression of the P2X(5)
      receptor subunit in DRG in different species including mouse, rat, cat and guinea
      pig. Immunohistochemistry showed that P2X(5) receptors exhibited low levels of
      immunostaining in rat DRG, but high levels in mouse and guinea pig. Only a few
      neurons were immunoreactive for P2X(5) receptors in cat. In mouse DRG, the P2X(5)
      receptor was expressed largely by medium-diameter neurons (42.9 %), less in small
      (29.3 %) and large (27.8 %) neurons. In contrast, in the guinea pig DRG, P2X(5)
      receptor expression was greatest in small-diameter (42.6 %), less in medium-
      (36.3 %) and large-diameter (21.1 %) neurons. Colocalization experiments revealed
      that, in mouse DRG, 65.5, 10.9 and 27.1 % of P2X(5) receptors were immunoreactive
      for NF-200, CGRP and calbindin, while only a few P2X(5)-immunoreactive (IR)
      neurons were coexpressed with IB4 or with NOS. In guinea pig DRG, a total of 60.5
      and 40.5 % of P2X(5)-IR neurons were coexpressed with IB4 or with CGRP, while
      20.3 and 24.5 % of P2X(5) receptors were coexpressed with NF-200 or with NOS.
      Only a few P2X(5)-IR neurons were coexpressed with calbindin in guinea pig DRG.
      It will be of great interest to clarify the relative physiological and
      pathophysiological roles of P2X(5) receptors.

PMID- 23160625
TI  - WHAMM is required for meiotic spindle migration and asymmetric cytokinesis in
      mouse oocytes.
AB  - WASP homolog associated with actin, membranes and microtubules (WHAMM) is a newly
      discovered nucleation-promoting factor that links actin and microtubule
      cytoskeleton and regulates transport from the endoplasmic reticulum to the Golgi
      apparatus. However, knowledge of WHAMM is limited to interphase somatic cells. In
      this study, we examined its localization and function in mouse oocytes during
      meiosis. Immunostaining showed that in the germinal vesicle (GV) stage, there was
      no WHAMM signal; after meiosis resumption, WHAMM was associated with the spindle
      at prometaphase I (Pro MI), metaphase I (MI), telophase I (TI) and metaphase II
      (MII) stages. Nocodazole and taxol treatments showed that WHAMM was localized
      around the MI spindle. Depletion of WHAMM by microinjection of specific short
      interfering (si)RNA into the oocyte cytoplasm resulted in failure of spindle
      migration, disruption of asymmetric cytokinesis and a decrease in the first polar
      body extrusion rate during meiotic maturation. Moreover, actin cap formation was
      also disrupted after WHAMM depletion, confirming the failure of spindle
      migration. Taken together, our data suggest that WHAMM is required for peripheral
      spindle migration and asymmetric cytokinesis during mouse oocyte maturation.

PMID- 23160626
TI  - Complete response of esophageal small cell carcinoma amrubicin treatment.
AB  - Small cell carcinoma of the esophagus (SmCCE) is a rare and aggressive disease
      known to have a poor prognosis. SmCCE patients are generally treated with a
      chemotherapeutic regimen for small cell lung cancer. Salvage therapy for patients
      with relapsed or refractory tumors has not yet been established. A 63-year-old
      man with extensive SmCCE was treated with chemotherapy consisting of cisplatin
      (CDDP) and irinotecan (CPT-11). After the second course of CPT-11/CDDP, the
      celiac lymph node increased in size. Amrubicin (AMR) as second-line chemotherapy
      was started. The patient had a complete response after the fifth course of AMR,
      resulting in an 8-month progression-free survival after initial administration.
      This case suggests that, as in small cell lung cancer, AMR is effective for
      SmCCE. 

PMID- 23160627
TI  - Three cases of IMP-type metallo-beta-lactamase-producing Enterobacter cloacae
      bloodstream infection in Japan.
AB  - We report three cases of IMP-type metallo-beta-lactamase-producing Enterobacter
      cloacae bloodstream infection, which showed minimum inhibitory concentration
      values for imipenem with 2 MUg/ml in all isolates. Although carbapenems were
      initiated empirically in all cases, two of three cases died. The Clinical and
      Laboratory Standards Institute lowered the breakpoints of carbapenems for
      Enterobacteriaceae in 2010. However, the previous breakpoints are still used in
      many clinical laboratories, which can result in failure to detect carbapenem
      resistant Enterobacteriaceae. Therefore, lower breakpoints of carbapenems should
      be used in clinical settings, and alternative tests for detecting metallo-beta
      lactamase such as polymerase chain reaction and immunochromatographic assays may
      contribute to better detection of carbapenem-resistant isolates. 

PMID- 23160630
TI  - Subaxial cervical juxtafacet cysts: single institution surgical experience and
      literature review.
AB  - OBJECTIVES: Juxtafacet cysts (JFCs) of the subaxial cervical spine are rare
      causes of neurological deficits. Their imaging characteristics, relationship to
      segmental instability, and potential for inducing acute symptomatic deterioration
      have only been described in a few case reports and small case series. The
      objective of the current study was to review the surgical experience at our
      center and across the literature to better define these variables. METHODS: A
      single-institution, multisurgeon series of 12 consecutive patients (mean age 63.4
      years, range 52-83 years) harboring 14 JFCs treated across 9 years was
      retrospectively reviewed. Clinical history, neurological status, preoperative
      imaging, operative findings, pathology, and postoperative outcomes were obtained
      from medical records. The mean follow up was 9.2 +/- 7.8 months. A literature
      review identified 35 studies with 89 previously reported cases of surgically
      treated subaxial cervical JFCs. RESULTS: Consistent with previously reported
      cases, most JFCs in our series involved the C7/T1 level. Nine patients reported
      axial neck pain, 12 patients had radicular symptoms, four patients had
      myelopathy, and one patient experienced rapid neurological decline attributable
      to cystic hemorrhage. Cyst expansion without hemorrhage caused subacute
      deterioration in one patient. All patients experienced sensory and/or motor
      improvement following surgical decompression. Preoperative axial neck pain
      improved in eight of nine patients (89 %). Seven out of 12 patients (58 %)
      underwent fusion either at the time of decompression (six patients) or at a
      delayed timepoint within the follow-up period (one patient). Prior history of
      cervical instrumentation, hypermobility on dynamic imaging, and other risk
      factors for segmental instability were more common in our series than in previous
      reports. CONCLUSIONS: Our findings lead us to advocate for early decompression
      rather than prolonged conservative treatment, for pre- and postoperative dynamic
      imaging, and for fusion in selected cases as an initial surgical consideration.

PMID- 23160629
TI  - Dental abnormalities in a mouse model for craniometaphyseal dysplasia.
AB  - Mice carrying a knock-in mutation (Phe377del) in the Ank gene replicate many
      skeletal characteristics of human craniometaphyseal dysplasia, including
      hyperostotic mandibles. Ank (KI/KI) mice have normal morphology of erupted molars
      and incisors but excessive cementum deposition with increased numbers of Ibsp-
      and Dmp1-positive cells on root surfaces. The cervical loops of adult Ank (KI/KI)
      lower incisors are at the level of the third molars, while they are close to the
      mandibular foramen in Ank (+/+) mice. Furthermore, Ank (KI/KI) incisors show
      decreased eruption rates, decreased proliferation of odontoblast precursors, and
      increased cell apoptosis in the stellate reticulum. However, their capability for
      continuous elongation is not compromised. Quantification of TRAP-positive cells
      in the apical ends of Ank (KI/KI) incisors revealed decreased osteoclast numbers
      and osteoclast surfaces. Bisphosphonate injections in Ank (+/+) mice replicate
      the Ank (KI/KI) incisor phenotype. These results and a comparison with the dental
      phenotype of Ank loss-of-function mouse models suggest that increased cementum
      thickness may be caused by decreased extracellular PPi levels and that the
      incisor phenotype is likely due to hyperostosis of mandibles, which distinguishes
      Ank (KI/KI) mice from the other Ank mouse models.

PMID- 23160631
TI  - Diagnosis and surgical strategy for sacral meningeal cysts with check-valve
      mechanism: technical note.
AB  - OBJECTIVE: There is agreement that symptomatic sacral meningeal cysts with a
      check-valve mechanism and/or large cysts representing space-occupying lesions
      should be treated surgically. This study investigated factors indicating a need
      for surgical intervention and surgical techniques for sacral meningeal cysts with
      a check-valve mechanism. METHODS: In ten patients presenting with sciatica and
      neurological deficits, myelography, computed tomography (CT) myelography, and
      magnetic resonance imaging (MR imaging) detected sacral meningeal cysts with a
      check-valve mechanism. One patient had two primary cysts. Ten cysts were type 2
      and one cyst was type 1. Nine of the ten patients had not undergone previous
      surgery, while the remaining case involved recurrent cyst. For the seven patients
      with normal (i.e., not huge or recurrent) type 2 cysts and no previous surgery
      (eight cysts), suture after collapse of the cyst wall was performed. For the
      recurrent type 2 cyst, duraplasty and suture with collapse of the cyst wall were
      performed to eliminate the check-valve mechanism. For the remaining type 2 cyst,
      a primary root was sacrificed because of the huge size of the cyst. For the type
      1 cyst, the neck of the cyst was ligated. RESULTS: In all cases, chief complaints
      disappeared immediately postoperatively and no deterioration of clinical symptoms
      has been seen after a mean follow-up of 27 months. CONCLUSIONS: The presence or
      absence of a check-valve mechanism is very important in determining the need for
      surgical intervention for sacral meningeal cysts.

PMID- 23160632
TI  - Grading of vestibular schwannomas and corresponding tumor volumes: ramifications
      for radiosurgery.
AB  - BACKGROUND: Patients with vestibular schwannomas (VS) are either assigned to
      watchful waiting, microsurgical resection, or radiosurgery. Decision making on
      how to proceed is based on parameters such as age, tumor growth, loss of hearing,
      and the tumor's Koos grading. METHODS: In order to correlate Koos grading with
      tumor volume, patient records of 235 patients with VS who underwent Gamma Knife
      radiosurgery (GKRS) were retrospectively reviewed. RESULTS: From 1994 to 2009,
      235 consecutive patients underwent GKRS for sporadic VS at the Zurich Gamma Knife
      Center. Median follow up was 62.8 +/- 33.0 months. Of the 235 tumors, 32 (13.6 %)
      were graded Koos I with a volume of 0.25 +/- 0.3 cc; 71 (30.2 %) were graded Koos
      II with a volume of 0.57 +/- 0.54 cc; 70 (29.8 %) were graded Koos III with a
      volume of 1.82 +/- 1.88 cc; and 62 (26.4 %) were graded Koos IV with a volume of
      4.17 +/- 2.75 cc. Tumor progression was defined as a volume increase > 20 % at 2
      years or later following GKRS. Overall tumor progression occurred in 21/235 (8.9
      %) patients at 3.4 +/- 0.9 years. Tumor progression did not differ statistically
      significantly in the various Koos grades: 1/32 (3.1 %) patients with VS Koos
      Grade I, 7/71 (9.8 %) patients with VS Koos Grade II, 6/70 (8.6 %) patients with
      VS Koos Grade III, and 7/62 (11.3 %) patients with VS Koos Grade IV. CONCLUSION:
      To our knowledge, this is the first work correlating the various Koos grades of
      VS to their respective tumor volumes. In our patients, tumor volumes of VS Koos
      Grade IV were limited because all of our patients were eligible for radiosurgery.
      In our series, the outcome following GKRS for patients with VS Koos Grade IV
      tumors did not differ from patients with VS Koos Grades I-III. We therefore
      suggest to limit Koos Grade IV VS to tumor volumes < 6 cc that may be eligible
      for radiosurgery, and introduce an additional VS Grade V for large VS with tumor
      volumes of > 6 cc that may not be eligible for radiosurgery.

PMID- 23160633
TI  - Experimental and theoretical studies of the interaction of gas phase nitric acid
      and water with a self-assembled monolayer.
AB  - Nitric acid in air is formed by atmospheric reactions of oxides of nitrogen and
      is removed primarily through deposition to surfaces, either as the gas or after
      conversion to particulate nitrate. Many of the surfaces and particles have
      organic coatings, but relatively little is known about the interaction of nitric
      acid with organic films. We report here studies of the interaction of gaseous
      HNO(3) with a self-assembled monolayer (SAM) formed by reacting 7
      octenyltrichlorosilane [H(2)C=CH(CH(2))(6)SiCl(3)] with the surface of a
      germanium infrared-transmitting attenuated total reflectance (ATR) crystal that
      was coated with a thin layer of silicon oxide (SiO(x)). The SAM was exposed at
      298 +/- 2 K to dry HNO(3) in a flow of N(2), followed by HNO(3) in humid N(2) at
      a controlled relative humidity (RH) between 20-90%. For comparison, similar
      studies were carried out using a similar crystal without the SAM coating. Changes
      in the surface were followed using Fourier transform infared spectroscopy (FTIR).
      In the case of the SAM-coated crystal, molecular HNO(3) and smaller amounts of
      NO(3)(-) ions were observed on the surface upon exposure to dry HNO(3). Addition
      of water vapor led to less molecular HNO(3) and more H(3)O(+) and NO(3)(-)
      complexed to water, but surprisingly, molecular HNO(3) was still evident in the
      spectra up to 70% RH. This suggests that part of the HNO(3) observed was
      initially trapped in pockets within the SAM and shielded from water vapor. After
      increasing the RH to 90% and then exposing the film to a flow of dry N(2),
      molecular nitric acid was regenerated, as expected from recombination of protons
      and nitrate ions as water evaporated. The nitric acid ultimately evaporated from
      the film. On the other hand, exposure of the SAM to HNO(3) and H(2)O
      simultaneously gave only hydronium and nitrate ions. Molecular dynamics
      simulations of defective SAMs in the presence of HNO(3) and water predict that
      nitric acid intercalates in defects as a complex with a single water molecule
      that is protected by alkyl chains from interacting with additional water
      molecules. These studies are consistent with the recently proposed hydrophobic
      nature of HNO(3). Under atmospheric conditions, if HNO(3) is formed in organic
      layers on surfaces in the boundary layer, e.g. through NO(3) or N(2)O(5)
      reactions, it may exist to a significant extent in its molecular form rather than
      fully dissociated to nitrate ions.

PMID- 23160634
TI  - MiR-125b inhibits tumor growth and promotes apoptosis of cervical cancer cells by
      targeting phosphoinositide 3-kinase catalytic subunit delta.
AB  - BACKGROUND: [corrected] microRNAs (miRNAs) are involved in cancer-related
      processes. The miRNA-125b (miR-125b) has been identified as miRNA over-expressed
      in a wide variety of cancers. However, the role of miR-125b in the context of
      cervical carcinoma remains unknown. METHODS: In this study, the effect of miR
      125b on the proliferation and apoptosis of human cervical cells was analyzed by
      MTT assay and Flow cytometry analysis. we identified phosphoinositide 3-kinase
      catalytic subunit delta (PIK3CD) as a novel miR-125b target. RESULTS:
      overexpression of miR- 125b in HeLa cervical cancer cells decreased cell
      proliferation, induced apoptosis and down-regulated expression of PIK3CD. To
      identify the mechanisms responsible, we investigated the PI3K/Akt pathway and
      found that PI3K, phospho-Akt, and phospho-mTOR were all down-regulated, while Bid
      was up-regulated in miR-125b-overexpressing subclones. In vivo, over expression
      of miR-125b in HeLa cells markedly reduced their ability to form tumors.
      CONCLUSION: these results suggest that miR-125b suppresses tumor growth activity
      by targeting the PI3K/ Akt/mTOR signaling pathway, and may provide a target for
      effective therapies.

PMID- 23160635
TI  - Three dimensional macroporous architectures and aerogels built of carbon
      nanotubes and/or graphene: synthesis and applications.
AB  - Carbon nanotubes and graphene are some of the most intensively explored carbon
      allotropes in materials science. This interest mainly resides in their unique
      properties with electrical conductivities as high as 10(4) S cm(-1), thermal
      conductivities as high as 5000 W m(-1) K and superior mechanical properties with
      elastic moduli on the order of 1 TPa for both of them. The possibility to
      translate the individual properties of these monodimensional (e.g. carbon
      nanotubes) and bidimensional (e.g. graphene) building units into two-dimensional
      free-standing thick and thin films has paved the way for using these allotropes
      in a number of applications (including photocatalysis, electrochemistry,
      electronics and optoelectronics, among others) as well as for the preparation of
      biological and chemical sensors. More recently and while recognizing the
      tremendous interest of these two-dimensional structures, researchers are noticing
      that the performance of certain devices can experience a significant enhancement
      by the use of three-dimensional architectures and/or aerogels because of the
      increase of active material per projected area. This is obviously the case as
      long as the nanometre-sized building units remain accessible so that the concept
      of hierarchical three-dimensional organization is critical to guarantee the mass
      transport and, as consequence, performance enhancement. Thus, this review aims to
      describe the different synthetic processes used for preparation of these three
      dimensional architectures and/or aerogels containing either any or both
      allotropes, and the different fields of application in which the particular
      structure of these materials provided a significant enhancement in the efficacy
      as compared to their two-dimensional analogues or even opened the path to novel
      applications. The unprecedented compilation of information from both CNT- and
      graphene-based three-dimensional architectures and/or aerogels in a single
      revision is also of interest because it allows a straightforward comparison
      between the particular features provided by each allotrope.

PMID- 23160636
TI  - Carrier-free nanoassemblies of a novel oxazolidinone compound FYL-67 display
      antimicrobial activity on methicillin-resistant Staphylococcus aureus.
AB  - In this work, a novel oxazolidinone compound FYL-67 was synthesized, and the
      obtained FYL-67 could form nanoassemblies in aqueous solution by a self-assembly
      method without using any carrier, organic solvent, or surfactant. The prepared
      FYL-67 nanoassemblies had a particle size of 264.6 +/- 4.3 nm. The FYL-67
      nanoassemblies can be lyophilized into a powder form without any cryoprotector or
      excipient, and the re-dissolved FYL-67 nanoassemblies are stable and homogeneous.
      The in vitro release profile showed a significant difference between rapid
      release of free FYL-67 and much slower and sustained release of FYL-67
      nanoassemblies. In vitro susceptibility tests were conducted in three strains of
      methicillin-susceptible Staphylococcus aureus (MSSA) and three strains of
      methicillin-resistant Staphylococcus aureus (MRSA), using linezolid as a positive
      control. FYL-67 nanoassemblies exhibited excellent in vitro activity, with a
      minimum inhibitory concentration (MIC) value of 0.5 MUg mL(-1) against MRSA. In
      the in vitro post-antibiotic effect (PAE) evaluation, FYL-67 nanoassemblies
      showed a more powerful effect than linezolid. Besides, in vitro cytotoxicity
      tests indicated that FYL-67 nanoassemblies had a very low cytotoxicity on HEK293
      cells and L02 cells. Furthermore, in both MSSA and MRSA systemic infection mouse
      models, FYL-67 nanoassemblies showed a lower ED(50) than linezolid. In a murine
      model of MRSA systemic infection, FYL-67 nanoassemblies displayed an ED(50) of
      less than 4.0 mg kg(-1), which is 2.3-fold better than that of linezolid. Our
      findings suggested that the FYL-67 nanoassemblies may be a potential drug
      candidate in MRSA therapy.

PMID- 23160637
TI  - The promoter of an A9 homolog from the conifer Cryptomeria japonica imparts male
      strobilus-dominant expression in transgenic trees.
AB  - KEY MESSAGE : GUS analysis in Cryptomeria japonica revealed that the CjMALE1
      promoter is activated in the male strobilus of C. japonica. Toward the
      development of male sterile technology for Cryptomeria japonica, a male strobilus
      dominant promoter of C. japonica was isolated. The CjMALE1 gene was isolated from
      a male strobilus-specific suppression subtractive hybridization (SSH) library,
      and the promoter was isolated by the TAIL-PCR method. To characterize the CjMALE1
      promoter, beta-glucuronidase (GUS)-fused genes were constructed and introduced
      into C. japonica using Agrobacterium tumefaciens. GUS expression from CjMALE1-2.5
      K (2,718 bp fragment)::GUS C. japonica and CjMALE1-1 K (1,029 bp fragment)::GUS
      C. japonica was detected in the tapetum and microspore mother cells. These
      promoter fragments were comparably active in the pre-meiotic stage of the male
      strobilus of C. japonica. Our analysis showed that the 1,029 bp promoter had all
      the cis-elements necessary for male strobilus-dominant expression of CjMALE1.
      When CjMALE1-1 K::GUS was introduced into Arabidopsis, GUS expression was
      detected in the same spatiotemporal pattern as in C. japonica. These results
      suggest that the CjMALE1 promoter is subject to transcriptional regulatory
      systems consisting of cis- and trans-elements that have been highly conserved
      during evolution.

PMID- 23160638
TI  - Development of an efficient transformation method by Agrobacterium tumefaciens
      and high throughput spray assay to identify transgenic plants for woodland
      strawberry (Fragaria vesca) using NPTII selection.
AB  - KEY MESSAGE : We developed an efficient Agrobacterium -mediated transformation
      method using an Ac/Ds transposon tagging construct for F. vesca and high
      throughput paromomycin spray assay to identify its transformants for strawberry
      functional genomics. Genomic resources for Rosaceae species are now readily
      available, including the Fragaria vesca genome, EST sequences, markers, linkage
      maps, and physical maps. The Rosaceae Genomic Executive Committee has promoted
      strawberry as a translational genomics model due to its unique biological
      features and transformability for fruit trait improvement. Our overall research
      goal is to use functional genomic and metabolic approaches to pursue high
      throughput gene discovery in the diploid woodland strawberry. F. vesca offers
      several advantages of a fleshy fruit typical of most fruit crops, short life
      cycle (seed to seed in 12-16 weeks), small genome size (206 Mbb/C), small plant
      size, self-compatibility, and many seeds per plant. We have developed an
      efficient Agrobacterium tumefaciens-mediated strawberry transformation method
      using kanamycin selection, and high throughput paromomycin spray assay to
      efficiently identify transgenic strawberry plants. Using our kanamycin
      transformation method, we were able to produce up to 98 independent kanamycin
      resistant insertional mutant lines using a T-DNA construct carrying an Ac/Ds
      transposon Launchpad system from a single transformation experiment involving
      inoculation of 22 leaf explants of F. vesca accession 551572 within approx. 11
      weeks (from inoculation to soil). Transgenic plants with 1-2 copies of a
      transgene were confirmed by Southern blot analysis. Using our paromomycin spray
      assay, transgenic F. vesca plants were rapidly identified within 10 days after
      spraying.

PMID- 23160639
TI  - Identification of genes preferentially expressed in wheat egg cells and zygotes.
AB  - KEY MESSAGE : Wheat genes differentially expressed in the egg cell before and
      after fertilization were identified. The data support zygotic gene activation
      before the first cell division in wheat. To have an insight into fertilization
      induced gene expression, cDNA libraries have been prepared from isolated wheat
      egg cells and one-celled zygotes. Two-hundred and twenty-six egg cell and 253
      zygote-expressed EST sequences were determined. Most of the represented
      transcripts were detected in the wheat egg cell or zygote transcriptome at the
      first time. Expression analysis of fourteen of the identified genes and three
      controls was carried out by real-time quantitative PCR. The preferential
      expression of all investigated genes in the female gametophyte-derived samples
      (egg cells, zygotes, two-celled proembryos, and basal ovule parts with synergids)
      in comparison to the anthers, and the leaves were verified. Three genes with
      putative signaling/regulatory functions were expressed at a low level in the egg
      cell but exhibited increased (2-to-33-fold) relative expression in the zygote and
      the proembryo. Genes with high EST abundance in cDNA libraries exhibited strong
      expression in the egg cell and the zygote, while the ones coding for unknown or
      hypothetical proteins exhibited differential expression patterns with
      preferential transcript accumulation in egg cells and/or zygotes. The obtained
      data support the activation of the zygotic genome before the first cell division
      in wheat.

PMID- 23160640
TI  - Evaluation of antioxidant activity of leafy vegetables and beans with myoglobin
      method.
AB  - KEY MESSAGE : Antioxidant activity of seven leafy vegetables and four beans
      against five reactive oxygen species and reactive nitrogen species was clearly
      characterized with a protocol using myoglobin as a reporter probe. Antioxidant
      activity of seven leafy vegetables and four beans against peroxyl radical,
      hydroxyl radical, hypochlorite ion, and peroxynitrite ion has been measured using
      myoglobin as a reporter probe (myoglobin method). Conventional DPPH method was
      also used to evaluate antioxidant activity of the samples. Difference of activity
      against different reactive oxygen species (ROS) and reactive nitrogen species
      (RNS) was characterized by plotting the data in a 5-axe cobweb chart. This plot
      clearly showed the characteristics of the antioxidant activity of the leafy
      vegetables and the beans. The samples examined in this work were categorized into
      four groups. (1) The samples showed high antioxidant activity against all ROS and
      RNS: daikon sprout, spinach, Qing-geng-cai, and onion. (2) The samples showed
      high antioxidant activity against peroxyl radical: red bean and soy bean. (3) The
      samples showed high antioxidant against hypochlorite ion: broccoli floret,
      cabbage, and Chinese cabbage. (4) The samples showed weak antioxidant activity
      against all ROS and RNS: cowpea and common beans. Our protocol is probably useful
      to characterize antioxidant activity of the crops of different cultivars, the
      crops obtained in different growing environments and growing seasons, the crops
      harvested at different age, and the crops stored in the different conditions, as
      well as the changes of activity during cooking process of the crops.

PMID- 23160642
TI  - Volume of supervised exercise training impacts glycaemic control in patients with
      type 2 diabetes: a systematic review with meta-regression analysis.
AB  - AIMS/HYPOTHESIS: Supervised exercise programmes improve glycaemic control in type
      2 diabetes, but training characteristics associated with reduction in HbA(1c)
      remain unclear. We conducted a systematic review with meta-regression analysis of
      randomised clinical trials (RCTs) assessing the association between intensity and
      volume of exercise training (aerobic, resistance or combined) and HbA(1c) changes
      in patients with type 2 diabetes. METHODS: Five electronic databases were
      searched (1980-2012) to retrieve RCTs of at least 12 weeks' duration, consisting
      of supervised exercise training vs no intervention, that reported HbA(1c) changes
      and exercise characteristics. Two independent reviewers conducted study selection
      and data extraction. RESULTS: Twenty-six RCTs (2,253 patients) met the inclusion
      criteria. In multivariate analysis, baseline HbA(1c) and exercise frequency
      explained nearly 58% of between-study variance. Baseline HbA(1c) was inversely
      correlated with HbA(1c) reductions after the three types of exercise training. In
      aerobic training, exercise volume (represented by frequency of sessions) was
      associated with changes in HbA(1c) (weighted r = -0.64), while no variables were
      correlated with glycaemic control induced by resistance training. In combined
      training, weekly volume of resistance exercise explained heterogeneity in
      multivariate analysis and was associated with changes in HbA(1c) levels (weighted
      r = -0.70). CONCLUSIONS/INTERPRETATION: Reduction in HbA(1c) is associated with
      exercise frequency in supervised aerobic training, and with weekly volume of
      resistance exercise in supervised combined training. Therefore, exercise volume
      is a major determinant of glycaemic control in patients with type 2 diabetes.

PMID- 23160644
TI  - Schizophrenia - it's not split personalities!

PMID- 23160643
TI  - HLA-dependent autoantibodies against post-translationally modified collagen type
      II in type 1 diabetes mellitus.
AB  - AIMS/HYPOTHESIS: In this study the involvement of oxidative stress in type 1
      diabetes mellitus autoimmunity and the possible association with rheumatoid
      arthritis (RA) was investigated. We tested the hypothesis that oxidative stress
      induced by chronic hyperglycaemia triggers post-translational modifications and
      thus the formation of neo-antigens in type 1 diabetes, similar to the ones found
      in RA. METHODS: Collagen type II (CII), a known autoantigen in RA, was treated
      with ribose and various reactive oxygen species (ROS). Levels of antibodies
      specific to native and ROS-modified CII (ROS-CII) were compared in type 1
      diabetes, type 2 diabetes and healthy controls, and related to the HLA genotype.
      RESULTS: Significantly higher binding to ROS-CII vs native CII was observed in
      type 1 diabetic patients possessing the HLA-DRB1*04 allele irrespective of
      variables of glucose control (blood glucose or HbA(1c)). Type 1 diabetic patients
      carrying a DRB1*04 allele with the shared epitope showed the highest risk for ROS
      CII autoimmunity, while the DRB1*0301 allele was protective. Conversely, native
      CII autoimmunity was not associated with any specific DRB1 allele. Positive and
      inverse seroconversion rates of response to ROS-CII were high in DRB1*04-positive
      type 1 diabetic patients. CONCLUSION: Hyperglycaemia and oxidative stress may
      trigger genetically controlled autoimmunity to ROS-CII and may explain the
      association between type 1 diabetes mellitus and RA.

PMID- 23160641
TI  - Exome sequencing-driven discovery of coding polymorphisms associated with common
      metabolic phenotypes.
AB  - AIMS/HYPOTHESIS: Human complex metabolic traits are in part regulated by genetic
      determinants. Here we applied exome sequencing to identify novel associations of
      coding polymorphisms at minor allele frequencies (MAFs) >1% with common metabolic
      phenotypes. METHODS: The study comprised three stages. We performed medium-depth
      (8*) whole exome sequencing in 1,000 cases with type 2 diabetes, BMI >27.5
      kg/m(2) and hypertension and in 1,000 controls (stage 1). We selected 16,192
      polymorphisms nominally associated (p < 0.05) with case-control status, from four
      selected annotation categories or from loci reported to associate with metabolic
      traits. These variants were genotyped in 15,989 Danes to search for association
      with 12 metabolic phenotypes (stage 2). In stage 3, polymorphisms showing
      potential associations were genotyped in a further 63,896 Europeans. RESULTS:
      Exome sequencing identified 70,182 polymorphisms with MAF >1%. In stage 2 we
      identified 51 potential associations with one or more of eight metabolic
      phenotypes covered by 45 unique polymorphisms. In meta-analyses of stage 2 and
      stage 3 results, we demonstrated robust associations for coding polymorphisms in
      CD300LG (fasting HDL-cholesterol: MAF 3.5%, p = 8.5 * 10(-14)), COBLL1 (type 2
      diabetes: MAF 12.5%, OR 0.88, p = 1.2 * 10(-11)) and MACF1 (type 2 diabetes: MAF
      23.4%, OR 1.10, p = 8.2 * 10(-10)). CONCLUSIONS/INTERPRETATION: We applied exome
      sequencing as a basis for finding genetic determinants of metabolic traits and
      show the existence of low-frequency and common coding polymorphisms with impact
      on common metabolic traits. Based on our study, coding polymorphisms with MAF
      above 1% do not seem to have particularly high effect sizes on the measured
      metabolic traits.

PMID- 23160645
TI  - MRI for the diagnosis of recurrent middle ear cholesteatoma in children--can we
      optimize the technique? Preliminary study.
AB  - BACKGROUND: Recurrent cholesteatoma after surgical excision occurs frequently in
      children. Until recently, a surgical second look was mandatory and considered as
      standard reference. MRI including a delayed T1 sequence after gadolinium
      injection and diffusion-weighted imaging (DWI) has proved its efficiency but has
      been evaluated mainly in adults. OBJECTIVE: Our purpose was to evaluate the
      accuracy of DWI to diagnose recurrence of cholesteatoma in children. MATERIALS
      AND METHODS: We evaluated prospectively with MRI 20 ears in 18 children who had
      had surgery for cholesteatoma. We compared DWI and delayed T1-weighted images
      following gadolinium administration with intraoperative or follow-up findings. We
      calculated the sensitivity and specificity of each sequence for the diagnosis of
      recurrent cholesteatoma. RESULTS: Sensitivity to diagnose recurrent cholesteatoma
      was 87% for both DWI and delayed post-gadolinium sequences, specificity was 71%
      and 83%, respectively. Adding both sequences, the sensitivity was 87%, the
      specificity 100%. There was one false negative probably due to small size
      recurrence. CONCLUSION: In our series, DWI was reliable to diagnose recurrent
      cholesteatoma in children and allows avoiding surgery when negative. However,
      because small recurrences less than 5 mm may be missed, follow-up must be
      prolonged (5 years).

PMID- 23160646
TI  - Contrast meals and malrotation in children-metal markers for improved accuracy.
AB  - Upper gastrointestinal contrast studies in children may cause false-positive or 
      negative diagnosis of intestinal malrotation from rotation of the patient. To
      alleviate this problem, skin markers can be used to reduce rotation of children
      undergoing this procedure, e.g., two metal markers (sheathed and sealed
      hypodermic needles) can be fixed onto the skin for gastro-intestinal contrast
      studies. We reviewed two Katz criteria influenced by patient rotation:
      duodenojejunal junction on or to the right of the left pedicle and pylorus to the
      left of the midline. A test group was positioned using markers; a control group
      without markers was positioned conventionally. Markers during a pilot study were
      applied, but positioning was done by helpers who had no on-screen visualization.
      In the test group, only 1 child (3%; n = 39) had a feature of malrotation. In the
      control group, there were features of malrotation in 12 children (25%; n = 48).
      No other features of malrotation were seen. The pilot study showed radiographic
      rotation with markers projecting off the midline in 78% of 58 children. This
      resulted in 48% of 58 patients having false features of malrotation. The use of
      metal skin markers results in reduction of rotational errors that could have
      caused false diagnosis of intestinal malrotation in children.

PMID- 23160647
TI  - Effect of antenatal growth on brain white matter maturation in preterm infants at
      term using tract-based spatial statistics.
AB  - BACKGROUND: White matter maturation of infants can be studied using diffusion
      tensor imaging (DTI). DTI of the white matter of the infant brain provides the
      best available clinical measures of brain tissue organisation and integrity.
      OBJECTIVE: The purpose of this study was to compare white matter maturation
      between preterm infants born small for gestational age (SGA) and preterms with
      weight appropriate for gestational age (AGA) at birth. MATERIALS AND METHODS: A
      total of 36 preterm infants were enrolled in the study (SGA, n = 9). A rater
      independent method called tract-based spatial statistics (TBSS) was used to
      assess white matter maturation. RESULTS: When measured by TBSS, the AGA infants
      showed higher fractional anisotrophy values in several white matter tracts than
      the SGA infants. Areas with significant differences included anterior thalamic
      radiation, corticospinal tract, forceps major and minor, inferior fronto
      occipital fasciculus, inferior longitudinal fasciculus, superior longitudinal
      fasciculus, uncinate fasciculus, and superior longitudinal fasciculus (temporal
      part). No significant difference was found for mean diffusivity. CONCLUSION: As
      an objective and user-independent method, TBSS confirmed that preterm infants
      with impaired antenatal growth have impaired white matter maturation compared to
      preterm infants with normal antenatal growth. The differences were mainly
      detected in radiations that are myelinated first.

PMID- 23160648
TI  - Challenging topics in child abuse imaging: improving our understanding.

PMID- 23160649
TI  - Thyroid hormone replacement therapy for primary hypothyroidism leads to
      significant improvement of renal function in chronic kidney disease patients.
AB  - BACKGROUND: The interactions between kidney and thyroid functions have been known
      for many years; however, there are few studies on the extent of the improvements
      and long-term changes of renal function after thyroid hormone replacement therapy
      (THRT) in chronic kidney disease (CKD) patients. The purpose of this study was to
      determine how THRT affects the estimated glomerular filtration rate (eGFR) in CKD
      patients with primary hypothyroidism. METHODS: A retrospective investigation was
      performed on 51 Japanese patients (15 men and 36 women) with primary
      hypothyroidism. The changes in eGFR after THRT were examined according to the
      existence of CKD and severity of thyroid function. RESULTS: eGFR increased
      rapidly over the first 6 months after THRT in CKD patents, which was followed by
      a plateau. There was a correlation between eGFR and the severity of
      hypothyroidism, which was independent of age, and eGFR in severely hypothyroid
      patients significantly increased up to levels that were similar to mildly
      hypothyroid patients after THRT. eGFR improved more in the lower initial eGFR
      group and increased about 30 % in CKD patients (47.5 +/- 7.7 vs. 62.1 +/- 9.5
      ml/min/1.73 m(2), P < 0.01). Moreover, eGFR in CKD patients with mild to moderate
      hypothyroidism was significantly increased compared to that in non-CKD patients.
      CONCLUSION: Our data suggested that hypothyroidism contributed to the reduction
      in eGFR, especially in CKD patients; therefore, patients with CKD should
      positively be examined for thyroid function, and appropriate THRT should be
      started if needed.

PMID- 23160650
TI  - Granulomatous interstitial nephritis.

PMID- 23160651
TI  - A combined high-field EPR and quantum chemical study on a weakly
      ferromagnetically coupled dinuclear Mn(III) complex. A complete analysis of the
      EPR spectrum beyond the strong coupling limit.
AB  - The electronic and magnetic properties of polynuclear complexes, in particular
      the magnetic anisotropy (zero field splitting, ZFS), the leading term of the spin
      Hamiltonian (SH), are commonly analyzed in a global manner and no attempt is
      usually made to understand the various contributions to the anisotropy at the
      atomic scale. This is especially true in weakly magnetically coupled systems. The
      present study addresses this problem and investigates the local SH parameters
      using a methodology based on experimental measurements and theoretical
      calculations. This work focuses on the challenging mono MU-oxo bis MU-acetato
      dinuclear Mn(III) complex: [Mn(2)(III)(MU-O)(MU-OAc)(2)L(2)](PF(6))(2) (with L =
      trispyrrolidine-1,4,7-triazacyclononane) (1), which is particularly difficult for
      EPR spectroscopy because of its large magnetic anisotropy and the weak
      ferromagnetic interaction between the two Mn(III) ions. High field (up to 12 T)
      and high frequency (190-345 GHz) EPR experiments have been recorded for 1 between
      5 and 50 K. These data have been analyzed by employing a complex Hamiltonian,
      which encompasses terms describing the local and inter-site interactions. Density
      functional theory and multireference correlated ab initio calculations have been
      used to estimate the ZFS of the Mn(III) ions (D(Mn) = +4.29 cm(-1), E(Mn)/D(Mn) =
      0.19) and the Euler angles reflecting the relative orientation of the ZFS tensor
      for each Mn(III) (alpha = -52 degrees , beta = 28 degrees , gamma = 3 degrees ).
      This analysis allowed the accurate determination of the local parameters: D(Mn) =
      +4.50 cm(-1), E(Mn)/D(Mn) = 0.07, alpha = -35 degrees , beta = 23 degrees , gamma
      = 2 degrees . The spin ladder approach has also been applied, but only the
      parameters of the ground spin state of 1 have been accurately determined (D(4) =
      +1.540 cm(-1), E(4)/D(4) = 0.107). This is not sufficient to allow for the
      determination of the local parameters. The validity and practical performance of
      both approaches have been discussed.

PMID- 23160652
TI  - The impact of a phase-change cooling vest on heat strain and the effect of
      different cooling pack melting temperatures.
AB  - Cooling vests (CV) are often used to reduce heat strain. CVs have traditionally
      used ice as the coolant, although other phase-change materials (PCM) that melt at
      warmer temperatures have been used in an attempt to enhance cooling by avoiding
      vasoconstriction, which supposedly occurs when ice CVs are used. This study
      assessed the effectiveness of four CVs that melted at 0, 10, 20 and 30  degrees C
      (CV0, CV10, CV20, and CV30) when worn by 10 male volunteers exercising and then
      recovering in 40  degrees C air whilst wearing fire-fighting clothing. When
      compared with a non-cooling control condition (CON), only the CV0 and CV10 vests
      provided cooling during exercise (40 and 29 W, respectively), whereas all CVs
      provided cooling during resting recovery (CV0 69 W, CV10 66 W, CV20 55 W and CV30
      29 W) (P < 0.05). In all conditions, skin blood flow increased when exercising
      and reduced during recovery, but was lower in the CV0 and CV10 conditions
      compared with control during exercise (observed power 0.709) (P < 0.05), but not
      during resting recovery (observed power only 0.55). The participants preferred
      the CV10 to the CV0, which caused temporary erythema to underlying skin, although
      this resolved overnight after each occurrence. Consequently, a cooling vest
      melting at 10  degrees C would seem to be the most appropriate choice for cooling
      during combined work and rest periods, although possibly an ice-vest (CV0) may
      also be appropriate if more insulation was worn between the cooling packs and the
      skin than used in this study.

PMID- 23160654
TI  - The perceptually regulated exercise test is sensitive to increases in maximal
      oxygen uptake.
AB  - The aim of this study was to assess the sensitivity of a perceptually regulated
      exercise test (PRET) to predict maximal oxygen uptake (VO2max) following an
      aerobic exercise-training programme. Sedentary volunteers were assigned to either
      a training (TG n = 16) or control (CG n = 10) group. The TG performed 30 min of
      treadmill exercise, regulated at 13 on the Borg Rating of Perceived Exertion
      (RPE) Scale, 3* per week for 8 weeks. All participants completed a 12-min PRET to
      predict VO2max followed by a graded exercise test (GXT) to measure VO2max before
      and after training. The PRET required participants to control the speed and
      incline on the treadmill to correspond to RPE intensities of 9, 11, 13 and 15.
      Predictive accuracy of extrapolation end-points RPE19 and RPE20 from a submaximal
      RPE range of 9-15 was compared. Measured VO2max increased by 17 % (p < 0.05) from
      baseline to post-intervention in TG. This was reflected by a similar change in
      [VO2max predicted from PRET when extrapolated to RPE 19 (baseline VO2max: 31.3 +/
      5.5, 30.3 +/- 9.5 mL kg(-1) min(-1); post-intervention VO2max: 36.7 +/- 6.4,
      37.4 +/- 7.9 mL kg(-1) min(-1), for measured and predicted values, respectively).
      There was no change in CG (measured vs. predicted VO2max: 39.3 +/- 6.5; 40.3 +/-
      8.2 and 39.2 +/- 7.0; 37.7 +/- 6.0 mL kg(-1) min(-1)) at baseline and post
      intervention, respectively. The results confirm that PRET is sensitive to
      increases in VO2max following aerobic training.

PMID- 23160653
TI  - Supra-physiological doses of testosterone affect membrane oxidation of human
      neutrophils monitored by the fluorescent probe C11-BODIPY581/591.
AB  - The purpose of this study was to determine the effects of supra-physiological
      doses of testosterone (TES) on membrane oxidation of activated human neutrophils
      in vitro using an innovative and sensitive technique: the real-time detection
      with the fluorescence probe C11-BODIPY(581/591). Methodological controls were
      performed with the lipid-soluble and powerful antioxidant astaxanthin at
      different neutrophil density cultures. Neutrophils from nine healthy young men
      (23.4 +/- 2.5 years, 174.4 +/- 7.0 cm height, and 78.3 +/- 7.0 kg weight) were
      isolated and treated with 0.1 or 10 MUM TES for 24 h and subsequently labeled
      with the free radical-sensitive probe C11-BODIPY(581/591) for monitoring membrane
      oxidation after neutrophil activation with phorbol-12-myristate-13-acetate (PMA).
      First-order exponential decay kinetic indicated that both 0.1 and 10 MUM TES
      severely increased baseline membrane oxidation in non-activated human neutrophils
      (compared to control). However, similar kinetics of membrane oxidation were
      observed in control and 0.1 MUM TES-treated neutrophils after PMA activation,
      whereas chemical activation did not alter the baseline higher rates of membrane
      oxidation in 10 MUM TES-treated neutrophils. The data presented here support the
      hypothesis that TES exerts distinct effects on the membrane oxidation of human
      neutrophils, depending on its dose (here, 10(2) to 10(4)-fold higher than
      physiological levels in men) and on PMA activation of the oxidative burst.
      Furthermore, this paper also presents an innovative application of the free
      radical-sensitive probe C11-BODIPY(581/591) for monitoring (auto-induced)
      membrane oxidation as an important parameter of viability and, thus,
      responsiveness of immune cells in inflammatory processes.

PMID- 23160655
TI  - Physical activity intensity and surrogate markers for cardiovascular health in
      adolescents.
AB  - We examined the impact of physical activity (PA) on surrogate markers of
      cardiovascular health in adolescents. 52 healthy students (28 females, mean age
      14.5 +/- 0.7 years) were investigated. Microvascular endothelial function was
      assessed by peripheral arterial tonometry to determine reactive hyperemic index
      (RHI). Vagal activity was measured using 24 h analysis of heart rate variability
      [root mean square of successive normal-to-normal intervals (rMSSD)]. Exercise
      testing was performed to determine peak oxygen uptake ([Formula: see text]) and
      maximum power output. PA was assessed by accelerometry. Linear regression models
      were performed and adjusted for age, sex, skinfolds, and pubertal status. The
      cohort was dichotomized into two equally sized activity groups (low vs. high)
      based on the daily time spent in moderate-to-vigorous PA (MVPA, 3,000-5,200
      counts(.)min(-1), model 1) and vigorous PA (VPA, >5,200 counts(.)min(-1), model
      2). MVPA was an independent predictor for rMSSD (beta = 0.448, P = 0.010), and
      VPA was associated with maximum power output (beta = 0.248, P = 0.016). In model
      1, the high MVPA group exhibited a higher vagal tone (rMSSD 49.2 +/- 13.6 vs.
      38.1 +/- 11.7 ms, P = 0.006) and a lower systolic blood pressure (107.3 +/- 9.9
      vs. 112.9 +/- 8.1 mmHg, P = 0.046). In model 2, the high VPA group had higher
      maximum power output values (3.9 +/- 0.5 vs. 3.4 +/- 0.5 W kg(-1), P = 0.012). In
      both models, no significant differences were observed for RHI and [Formula: see
      text]. In conclusion, in healthy adolescents, PA was associated with beneficial
      intensity-dependent effects on vagal tone, systolic blood pressure, and exercise
      capacity, but not on microvascular endothelial function.

PMID- 23160658
TI  - Intriguing substituent effect in modified Hoveyda-Grubbs metathesis catalysts
      incorporating a chelating iodo-benzylidene ligand.
AB  - A series of modified Hoveyda-Grubbs catalysts incorporating a chelating iodo
      benzylidene ligand were prepared and characterized. The presence of electron
      withdrawing ring substituents in the para position to the iodide was found to
      decrease the catalytic activity, revealing that dissociation of the Ru...I-Ar
      bond is not the rate-determining step.

PMID- 23160656
TI  - Effect of whole-body mild-cold exposure on arterial stiffness and central
      haemodynamics: a randomised, cross-over trial in healthy men and women.
AB  - Aortic pulse wave velocity (PWV) and augmentation index (AIx) are independent
      predictors of cardiovascular risk and mortality, but little is known about the
      effect of air temperature changes on these variables. Our study investigated the
      effect of exposure to whole-body mild-cold on measures of arterial stiffness
      (aortic and brachial PWV), and on central haemodynamics [including augmented
      pressure (AP), AIx], and aortic reservoir components [including reservoir and
      excess pressures (P ex)]. Sixteen healthy volunteers (10 men, age 43 +/- 19
      years; mean +/- SD) were randomised to be studied under conditions of 12  degrees
      C (mild-cold) and 21  degrees C (control) on separate days. Supine resting
      measures were taken at baseline (ambient temperature) and after 10, 30, and 60
      min exposure to each experimental condition in a climate chamber. There was no
      significant change in brachial blood pressure between mild-cold and control
      conditions. However, compared to control, AP [+2 mmHg, 95 % confidence interval
      (CI) 0.36-4.36; p = 0.01] and AIx (+6 %, 95 % CI 1.24-10.1; p = 0.02) increased,
      and time to maximum P ex (a component of reservoir function related to timing of
      peak aortic in-flow) decreased (-7 ms, 95 % CI -15.4 to 2.03; p = 0.01) compared
      to control. Yet there was no significant change in aortic PWV (+0.04 m/s, 95 % CI
      -0.47 to 0.55; p = 0.87) or brachial PWV (+0.36 m/s; -0.41 to 1.12; p = 0.35)
      between conditions. We conclude that mild-cold exposure increases central
      haemodynamic stress and alters timing of peak aortic in-flow without
      differentially affecting arterial stiffness.

PMID- 23160657
TI  - Circulating MMP-9 during exercise in humans.
AB  - Matrix metalloproteinase 9 (MMP-9) is a member of a family of zinc-dependent
      endopeptidases capable of degrading extracellular matrix (ECM) proteins. A single
      bout of exercise increases levels of activated MMP-9 in skeletal muscle and in
      the circulation. However, whether the exercise-induced activation of MMP-9 is
      associated with ECM remodeling and the cellular source behind MMP-9 in the
      circulation is not known. In the present study ten healthy male subjects
      performed a single cycle exercise bout and arterial and venous femoral blood was
      collected. To test if exercise induces basal lamina degradation and if
      circulating levels of MMP-9 is related to a release from the exercising muscle,
      arteriovenous differences of collagen IV and MMP-9 were measured by ELISA and
      zymography, respectively. Furthermore, markers of neutrophil degranulation
      elastase and neutrophil gelatinase-associated lipocalin (NGAL) were measured by
      ELISA. Plasma levels of collagen IV increased during the exercise bout and an
      increased arteriovenous difference of collagen IV was noted at 27 min of
      exercise. Plasma levels of MMP-9 were increased at both 27 and 57 min of exercise
      but no arteriovenous difference was noted. No changes over time were detected for
      elastase and NGAL. The observed release of collagen IV from the exercising muscle
      indicate basal lamina turnover following a single bout of exercise. No detectable
      release of MMP-9 was observed, suggesting that the increase in plasma MMP-9 could
      come from a source other than the skeletal muscle.

PMID- 23160659
TI  - Individual and contextual factors associated with patterns of aggression and peer
      victimization during middle school.
AB  - Peer victimization is a common problem among adolescents that has been linked to
      a variety of adjustment problems. Youth involved in peer victimization represent
      a heterogeneous group who may differ not only in their levels of victimization
      and perpetration, but also in the factors that influence their behavior. The
      current study used latent class analysis (LCA) to identify subgroups of
      aggressive and victimized youth, and to examine social-cognitive and
      environmental factors that differ across these subgroups. Participants were a
      predominantly African-American (i.e., 68 %) sample of 502 sixth, seventh, and
      eighth graders (45 % male, Mean age = 12.6 years) attending three urban public
      middle schools, who completed self-report measures of aggression, victimization,
      and associated individual and contextual factors. LCA identified four classes of
      adolescents representing non-victimized aggressors, aggressive-victims,
      predominantly victimized youth, and well-adjusted youth. Class differences were
      found on measures of beliefs supporting fighting, beliefs against fighting,
      perceived effectiveness of inept nonviolent responses to conflict, behavioral
      intentions to engage in aggressive and nonviolent behavior, self-efficacy for
      nonviolent behavior, and peer and parental support for aggression and
      nonviolence. For example, within the two classes of victimized youth, aggressive
      victims reported greater intentions to engage in physical aggression and inept
      nonviolent behavior, and were more likely to agree with beliefs supporting the
      use of instrumental and reactive aggression, and beliefs that fighting is
      sometimes necessary compared to predominantly victimized youth. These findings
      emphasize the importance of developing preventive interventions that target the
      specific needs of distinct subgroups of adolescents.

PMID- 23160660
TI  - Different trajectories of depressive symptoms in children and adolescents:
      predictors and differences in girls and boys.
AB  - The development of depressive symptoms in childhood and adolescence can follow
      different pathways. This study examined heterogeneity in the development of self
      reported depressive symptoms and the predictive influence of mothers' depressive
      symptoms, the number of life events, and loss events via growth mixture modeling
      over a four-year period in a large community sample of German children and
      adolescents (N = 3,902; mean age 11.39 years; 49.6% female). This procedure was
      conducted for the total sample as well as for separate samples of girls and boys.
      Four different classes of trajectories for the total and the girls' model were
      identified, but only three classes for the boys. Girls showed higher intercepts
      and stronger increases in symptoms over time, whereas boys displayed stronger
      decreases. In the total model, mothers' depressive symptoms and the number of
      life events significantly increased the level of depressive symptoms. In the
      gender models, only mothers' depressive symptoms showed significant influence on
      the level of symptoms in girls and boys, whereas for life events this was only
      true for boys. In every model, the significant predictors discriminated at least
      between some classes. Loss events showed no significant influence in any model.
      In sum, there are meaningful differences in the development of depressive
      symptoms in girls and boys. These results have several implications for
      prevention and future research.

PMID- 23160661
TI  - The longitudinal relationship between peer violence and popularity and
      delinquency in adolescent boys: examining effects by family functioning.
AB  - Mapping the relationship of peer influences and parental/family characteristics
      on delinquency can help expand the understanding of findings that show an
      interdependence between peer and family predictors. This study explored the
      longitudinal relationship between two characteristics of peer relationships
      (violence and perceived popularity) with subsequent individual delinquency and
      the moderating role of family characteristics (cohesion and parental monitoring)
      using data from the Chicago Youth Development Study. Participants were 364 inner
      city residing adolescent boys (54% African American; 40% Hispanic). After
      controlling for the effects of age and ethnicity, peer violence is positively
      related to boys' delinquency. The effect of popularity depends on parental
      monitoring, such that the relationship between popularity and delinquency is
      positive when parental monitoring is low, but there is no relationship when
      parental monitoring is high. Furthermore, parental monitoring contributes to the
      relationship between peer violence and delinquency such that there is a stronger
      relationship when parental monitoring is low. Additionally, there is a stronger
      relationship between peer violence and delinquency for boys from high cohesive
      families. Findings point to the value of attention to multiple aspects of peer
      and family relationships in explaining and intervening in the risk for
      delinquency. Furthermore, findings indicate the importance of family-focused
      interventions in preventing delinquency.

PMID- 23160662
TI  - Evaluation of shearwave elastography for the characterisation of focal liver
      lesions on ultrasound.
AB  - OBJECTIVES: To determine the elasticity characteristics of focal liver lesions
      (FLLs) by shearwave elastography (SWE). METHODS: We used SWE in 108 patients with
      161 FLLs and in the adjacent liver for quantitative and qualitative FLLs
      stiffness assessment. The Mann-Whitney test was used to assess the difference
      between the groups of lesions where a P value less than 0.05 was considered
      significant. RESULTS: SWE acquisitions failed in 22 nodules (14 %) in 13
      patients. For the 139 lesions successfully evaluated, SWE values were (in kPa),
      for the 3 focal fatty sparings (FFS) 6.6 +/- 0.3, for the 10 adenomas 9.4 +/-
      4.3, for the 22 haemangiomas 13.8 +/- -5.5, for the 16 focal nodular hyperplasias
      (FNHs) 33 +/- -14.7, for the 2 scars 53.7 +/- 4.7, for the 26 HCCs 14.86 +/- 10,
      for the 53 metastasis 28.8 +/- 16, and for the 7 cholangiocarcinomas 56.9 +/-
      25.6. FNHs had significant differences in stiffness compared with adenomas (P =
      0.0002). Fifty percent of the FNHs had a radial pattern of elevated elasticity. A
      significant difference was also found between HCCs and cholangiocarcinomas
      elasticity (P = 0.0004). CONCLUSIONS: SWE could be useful in differentiating FNHs
      and adenomas, or HCCs and cholangiocarcinomas by ultrasound.

PMID- 23160663
TI  - Comparison of the diagnostic value of MR imaging and ophthalmoscopy for the
      staging of retinoblastoma.
AB  - PURPOSE: To compare the diagnostic value of magnetic resonance (MR) imaging and
      ophthalmoscopy for staging of retinoblastoma. METHODS: MR and ophthalmoscopic
      images of 36 patients who underwent enucleation were evaluated retrospectively
      following institutional review board approval. Histopathology being the standard
      of reference, the sensitivity and specificity of both diagnostic modalities were
      compared regarding growth pattern, iris neoangiogenesis, retinal detachment,
      vitreous seeds and optic nerve invasion. Data were analysed via McNemar's test.
      RESULTS: Both investigations showed no significant difference in accuracy for the
      detection of different tumour growth patterns (P = 0.80). Vitreous seeding
      detection was superior by ophthalmoscopy (P < 0.001). For prelaminar optic nerve
      invasion, MR imaging showed similar sensitivity as ophthalmoscopy but increased
      specificity of 40 % (CI 0.12-0.74) vs. 20 % (0.03-0.56). MR detected optic nerve
      involvement past the lamina cribrosa with a sensitivity of 80 % (0.28-0.99) and a
      specificity of 74 % (0.55-0.88). The absence of optic nerve enhancement excluded
      histopathological infiltration, but the presence of optic nerve enhancement
      included a high number of false positives (22-24 %). CONCLUSIONS: Ophthalmoscopy
      remains the method of choice for determining extent within the globe while MR
      imaging is useful for evaluating extraocular tumour extension. Thus, both have
      their own strengths and contribute uniquely to the staging of retinoblastoma. KEY
      POINTS: * Ophthalmoscopy: method of choice for determining extent of
      retinoblastoma within the globe. * MR imaging provides optimal evaluation of
      extrascleral and extraocular tumour extension. * Positive enhancement of the
      optic nerve on MRI does not necessarily indicate involvement.

PMID- 23160664
TI  - Partial splenic embolisation using n-butyl cyanoacrylate: intraprocedural
      evaluation by magnetic resonance imaging.
AB  - OBJECTIVES: To evaluate the use of diffusion-weighted imaging (DWI) for
      estimating infarcted splenic volume during partial splenic embolisation (PSE)
      using n-butyl cyanoacrylate (NBCA). METHODS: Twenty consecutive patients (57.2 +/
      11.7 years) with hypersplenism underwent PSE. Intrasplenic branches were
      embolised using NBCA via a 2.1-French microcatheter aiming at infarction of 50 to
      80 % of total splenic volume. Immediately after PSE, signal intensities (SI) of
      embolised and non-embolised splenic parenchyma were measured on DWI. Semi
      automated volumetry (SAV) on DWI was compared with conventional manual volumetry
      (MV) on contrast-enhanced CT 1 week after PSE. Platelet counts were recorded
      before and after PSE. RESULTS: The SI on DWI in the embolised parenchyma
      decreased significantly (P < 0.01) to 24.7 +/- 8.1 % as compared to non-embolised
      parenchyma. SAV and MV showed a strong correlation (r = 0.913 before PSE, r =
      0.935 after PSE, P < 0.01) and significant (P < 0.01) reduction of normal splenic
      volume was demonstrated on both SAV (71.9 +/- 12.4 %) and MV (73.6 +/- 9.3 %)
      after PSE. Based on the initial SAV, three patients (15 %) underwent additional
      branch embolisation to reach sufficient infarction volume. Platelet counts
      elevated significantly (522.8 +/- 209.1 %, P < 0.01) by 2 weeks after PSE. No
      serious complication was observed. CONCLUSION: Immediate SI changes on DWI after
      PSE allowed semi-automated splenic volumetry on site. KEY POINTS: * Partial
      splenic embolisation (PSE) is an important interventional technique for
      hypersplenism * Diffusion-weighted MR reveals an immediate decrease in signal in
      the embolised parenchyma * Such signal reduction permits semi-automated splenic
      volumetry on site. * This allows precise quantification of the amount of
      parenchyma infarcted, avoiding additional PSE.

PMID- 23160666
TI  - Measuring inter-observer agreement in contour delineation of medical imaging in a
      dummy run using Fleiss' kappa.
AB  - BACKGROUND: In medical imaging used for planning of radiation therapy, observers
      delineate contours of a treatment volume in a series of images of uniform slice
      thickness. OBJECTIVE: To summarize agreement in contouring between an arbitrary
      number of observers by a single number, we generalized the kappa index proposed
      by Zijdenbos et al. (1994). METHODS: Observers characterized voxels by allocating
      them to one of two categories, inside or outside the contoured region. Fleiss'
      kappa was used to measure association between n indistinguishable observers.
      Given the number Vi of voxels contoured by exactly i observers (i = 1, ..., n ),
      the resulting overall kappa is representable as a ratio of weighted sums of the
      Vi . RESULTS: Overall kappa was applied to analyze inter-center variations in a
      multicenter trial on radiotherapy planning in patients with locally advanced lung
      cancer. A contouring dummy run was performed within the quality assurance
      program. Contouring was done twice, once before and once after a training
      program. Observer agreement was enhanced from 0.59 (with a 95% confidence
      interval (CI) of 0.51-0.67) to 0.69 (95% CI 0.59-0.78). CONCLUSION: By contrast
      to average pairwise indices, overall kappa measures observer agreement for more
      than two observers using the full information about overlapping volumes, while
      not distinguishing between observers. It is particularly adequate for measuring
      observer agreement when identification of observers is not possible or desirable
      and when there is no gold standard.

PMID- 23160665
TI  - Murine whole-organ immune cell populations revealed by multi-epitope-ligand
      cartography.
AB  - Multi-epitope-ligand cartography (MELC) is an innovative high-throughput
      fluorescence microscopy-based method. A tissue section is analyzed through a
      repeated cycling of (1) incubation with a fluorophore-labeled antibody, (2)
      fluorescence imaging, and (3) soft bleaching. This method allows staining of the
      same tissue section with up to 100 fluorescent markers and to analyze their
      toponomic expression using further image processing and pixel-precise overlay of
      the corresponding images. In this study, we adapted this method to identify a
      large panel of murine leukocyte subpopulations in a whole frozen section of a
      peripheral lymph node. Using the resulting antibody library, we examined non
      inflamed versus inflamed tissues of brain and spinal cord in the experimental
      autoimmune encephalomyelitis (EAE) model. The presence and activity of specific
      leukocyte subpopulations (different T cell subpopulations, dendritic cells,
      macrophages, etc.) could be assessed and the cellular localizations and the
      corresponding activation status in situ were investigated. The results were then
      correlated with quantitative RT-PCR.

PMID- 23160667
TI  - Proteomic profiling to identify prognostic biomarkers in heart failure.
AB  - BACKGROUND: The ability to predict mode, as well as risk, of death in left
      ventricular systolic dysfunction (LVSD) is important, as the clinical and cost
      effectiveness of implantable cardioverter defibrillators (ICD) therapy depends on
      its use in appropriately selected patient populations. The value of a proteomic
      approach in identifying prognostic biomarkers in LVSD is unknown. The aims of
      this pilot study were to use proteomic techniques to identify serum biomarkers
      associated with LVSD and to prospectively explore their association with
      prognosis. PATIENTS AND METHODS: Serum was analysed by surface-enhanced laser
      desorption ionisation time-of-flight mass spectrometry (SELDI-TOF MS) in patients
      with (n=78) and without (n=45) systolic heart failure (SHF). Spectra were
      compared to identify differentially expressed signal peaks as potential biomarker
      indicators. The ability of these peaks to predict all-cause mortality and
      survival with appropriate ICD therapy was then tested prospectively in patients
      with ICDs, on the background of LVSD (n=141). RESULTS: For the identification
      stage spectra (2-200 kDa) from SHF and control patients were randomly separated
      into two equally sized discovery and validation sets. Six protein peaks were
      identified that were differentially expressed in SHF in both sets. In the
      prospective phase, during a mean follow-up of 15+/-3 months, 11 patients died and
      39 survived with appropriate ICD therapy. Five out of the six proteomic
      biomarkers predicted all-cause mortality but none predicted appropriate ICD
      therapy. CONCLUSION: These results provide proof-of-principle and are supportive
      of the SELDI proteomic approach as a high-throughput screening tool in
      identifying potentially prognostic protein peaks in patients with LVSD.

PMID- 23160668
TI  - Acclimatization of mice to different cage types and social groupings with respect
      to fecal secretion of IgA and corticosterone metabolites.
AB  - Stress associated with transport and change of environment may have widespread
      effects on physiological parameters in laboratory animals. To investigate the
      time needed for mice to acclimatize to a new environment, based on fecal IgA and
      corticosterone excretion, eightweek-old BALB/c mice of both genders were housed
      either in groups of eight in different cage types in open conventional cages, in
      Individual Ventilated Cages (IVC), in open conventional cages inside a plastic
      isolator, or in different group sizes (8, 4, 8, 10 or 12 mice in each group) in
      open conventional cages. Feces were collected from each cage on routine cage
      changing. There was no significant difference in corticosterone excretion in
      feces between animals housed in the different cage types or between animals
      housed in different group sizes. IgA excretion for both males and females was
      found to be affected by transfer of mice into a novel cage, and it was found that
      it takes at least four weeks for the mice to acclimatize to a new environment
      with respect to this parameter.

PMID- 23160670
TI  - Sequential changes in the expression of Wnt- and Notch-related genes in the
      vagina and uterus of ovariectomized mice after estrogen exposure.
AB  - Estrogen regulates morphological changes in reproductive organs, such as the
      vagina and uterus, during the estrous cycles in mice. Estrogen depletion by
      ovariectomy in adults results in atrophy accompanied by apoptosis in vaginal and
      uterine cells, while estrogen treatment following ovariectomy elicits cell
      proliferation in both organs. Sequential changes in mRNA expression of wingless
      related MMTV integration site (Wnt) and Notch signaling genes were analyzed in
      the vagina and uterus of ovariectomized adult mice after a single injection of
      17beta-estradiol to provide understanding over the molecular basis of differences
      in response to estrogen in these organs. We found estrogen-dependent up
      regulation of Wnt4, Wnt5a and p21 and down-regulation of Wnt11, hairy/enhancer-of
      split related with YRPW motif-1 (Hey1) and delta-like 4 (Dll4) in the vagina, and
      up-regulation of Wnt4, Wnt5a, Hey1, Heyl, Dll1, p21 and p53 and down-regulation
      of Wnt11, Hey2 and Dll4 in the uterus. The expression of Wnt4, Hey1, Hey2, Heyl,
      Dll1 and p53 showed different patterns after the estrogen injection. Expression
      patterns for Wnt5a, Wnt11, Dll4 and p21 in the vagina and uterus were similar,
      suggesting that these genes are involved in the proliferation of cells in both
      those organs in mice.

PMID- 23160669
TI  - The zebrafish--Danio rerio--is a useful model for measuring the effects of small
      molecule mitigators of late effects of ionizing irradiation.
AB  - BACKGROUND/AIM: Use of zebrafish models may decrease the cost of screening new
      irradiation protectors and mitigators. MATERIALS AND METHODS: Zebrafish (Danio
      rerio) models were tested for screening water-soluble radiation protectors and
      mitigators. Irradiation of embryos and monitoring survival, and measuring
      fibrosis of the caudal musculature of adults allowed for testing of acute and
      late effects, respectively. RESULTS: Incubation of zebrafish embryos either
      before or after irradiation in ethyl pyruvate (1 mM) increased survival.
      Irradiation of adults to 15 to 75 Gy, delivered in single-fraction at 13 Gy/min,
      showed dose-dependent fibrosis at 30 days, quantitated as physiological decrease
      in swimming tail movement, and histopathological detection of collagen deposition
      in the dorsal musculature. Continuous administration of small-molecule
      radioprotector drugs in the water after irradiation reduced both acute and
      chronic injuries. CONCLUSION: The zebrafish is cost-effective for screening new
      radiation countermeasures.

PMID- 23160671
TI  - Inhibition of biofilm formation on ventilation tubes by surface modification.
AB  - AIM: The purpose of this study was to modify the surface characteristics of a
      ventilation tube (VT) with polyethylene glycol (PEG) coating and to evaluate the
      effect on biofilm formation. MATERIALS AND METHODS: VTs made of polyethylene were
      coated with PEG. Streptococcus pneumonia R6 strain was used and a crystal violet
      assay was carried out to measure the in vitro and in vivo biofilm formation of
      rats bearing VTs. RESULTS: In the in vitro experiment, the optical density of the
      uncoated VT was 0.34+/-0.09 and the optical density of the PEG-grafted VT was
      0.22+/-0.06 (p<0.05). In the in vivo experiment, the optical density of the
      uncoated VT was 0.54+/-0.12 and that of the PEG-grafted VT was 0.32+/-0.13
      (p<0.05). Scanning electron microscopy showed that surface modification,
      roughness and hydrophilic characteristics improved and biofilm formation
      decreased. CONCLUSION: The reduced biofilm formation on the VT may be explained
      by the alteration of surface tension and roughness induced by PEG coating.

PMID- 23160672
TI  - Accumulation and pharmacokinetics of estrogenic chemicals in the pre- and post
      hatch embryos of the frog Rana rugosa.
AB  - Amphibian eggs spawned in water are exposed immediately to various chemicals
      present in their water. The present study aimed to investigate the accumulation
      and pharmacokinetics of 17alpha-ethynylestradiol (EE(2)), bisphenol A (BPA), and
      nonylphenol (NP), as well as 17beta-estradiol (E(2)), in the pre-hatch and post
      hatch embryos of the frog Rana rugosa. Fertilized eggs were exposed to chemicals
      at a final concentration of 500 nM in breeding water for two days, then the
      embryos with jelly coats were reared in fresh-breeding water without
      supplementation of the xenoestrogens for six more days. All exogenous chemicals
      were concentrated in the embryo body at two days after fertilization, whereas
      their concentrations in the jelly coat were the same as those in the breeding
      water. The bioconcentration factors for E(2), EE(2), BPA, and NP were 217.9,
      170.2, 382.3, and 289.1, respectively, suggesting that the estrogenic chemicals
      were concentrated in the embryo body through the jelly coat.

PMID- 23160673
TI  - Histology, bioenergetics and oxidative stress in mouse liver exposed to N
      diethylnitrosamine.
AB  - BACKGROUND: A mouse model in which N-diethylnitrosamine (DEN) induces
      Hepatocellular carcinoma (HCC) has histological and genetic resemblance to human
      tumours. MATERIAL AND METHODS: Male ICR mice were divided into control (n=10) and
      DEN-treated (n=10) groups. DEN was administered via intraperitoneal injection,
      once a week, for eight consecutive weeks. Animals were euthanized seven weeks
      after the last administration of DEN and their livers were collected. Plasma
      albumin, total bilirubin, alanine transaminase and aspartate aminotransferase
      activity were all measured and liver mitochondrial bioenergetics and oxidative
      stress were also evaluated. RESULTS: Histologically, pre-neoplastic lesions were
      identified in the livers of mice from the DEN group. Total plasma bilirubin
      increased significantly in the group exposed to DEN and mitochondrial complex I
      and IV were significantly inhibited (p=0.0403 and p=0.0053, respectively).
      CONCLUSION: DEN induced changes in liver bioenergetics and antioxidant capacity
      towards reactive oxygen species, seven weeks after administration. At this stage,
      liver tissues in mice exposed to DEN still had the ability to counteract the
      oxidative effects of DEN by increasing the activity of antioxidant enzymes.

PMID- 23160674
TI  - Palliative intralesional interleukin-2 treatment in dogs with urinary bladder and
      urethral carcinomas.
AB  - AIM: The investigation of the influence of intralesional interleukin-2 (IL-2) on
      the clinical course and tumor progression in dogs suffering from urinary bladder
      and urethral carcinomas. MATERIALS AND METHODS: Medical records of 25 dogs
      diagnosed with advanced transitional cell carcinomas (TCC) were retrospectively
      reviewed. In 14 dogs, intralesional IL-2 treatment was performed by
      transabdominal ultrasound-guided injection. Seven dogs underwent cytoreductive
      surgery, followed by IL-2 injection into the tumor bed. All dogs received long
      term non-steroidal anti-inflammatory drugs. RESULTS: Adverse effects associated
      with IL-2 treatment were not observed. At re-examination, 17 dogs showed marked
      clinical improvement and regression of tumor size. Four dogs were in complete
      remission. CONCLUSION: Intralesional IL-2 application is a safe and minimally
      invasive palliative treatment option in dogs suffering from advanced transitional
      cell carcinoma when surgical cure is impossible. Prognosis depends on tumor
      localization and feasibility of concomitant cytoreductive surgery.

PMID- 23160675
TI  - No compensation in VEGF expression follows antisense suppression of BCL-2
      activity.
AB  - Antisense oligonucleotides (oligos) have been employed against prostate cancer
      models targeting growth-regulatory proteins, and at least one oligo (against bcl
      2) has reached clinical trial. We previously found that, in LNCaP cells, mono-
      and bispecific oligos, which comparably suppressed the expression of bcl-2,
      compensated with suppression of caspase-3 (apoptosis promoter) activity, and
      enhanced the expression of the androgen receptor (AR) and its p300 and IL-6 co
      activators. In addition, prostate-specific membrane antigen (PSMA) and (possibly
      its regulator) interferon (IFN) were elevated. A total of 14 proteins distributed
      between regulators of apoptosis, androgen regulation, differentiation antigens
      and autocrine-mediated growth have previously been examined. We extend these
      findings to include vascular endothelial growth factor (VEGF), a promoter of
      angiogenesis, which is not significantly altered through compensation, and
      therefore would not need additional regulation for suppressive bcl-2 therapy to
      be effective (like caspase-3).

PMID- 23160676
TI  - Comparative inhibitory effects of magnolol, honokiol, eugenol and bis-eugenol on
      cyclooxygenase-2 expression and nuclear factor-kappa B activation in RAW264.7
      macrophage-like cells stimulated with fimbriae of Porphyromonas gingivalis.
AB  - BACKGROUND: The anti-inflammatory activity of magnolol and related compounds is
      currently a focus of interest. In the present study, the inhibitory effects of
      these compounds on cyclooxygenase (COX-2) expression and nuclear factor-kappa B
      (NF-kappaB) activation were investigated in RAW264.7 macrophage-like cells
      stimulated with the fimbriae of Porphyromonas gingivalis, an oral anaerobe.
      MATERIALS AND METHODS: The cytotoxicity of magnolol, honokiol, eugenol and bis
      eugenol against RAW264.7 cells was determined using a cell counting kit (CCK-8).
      The regulatory effect of these compounds on the expression of COX-2 mRNA,
      stimulated by exposure to the fimbriae was investigated by real-time polymerase
      chain reaction (PCR). NF-kappaB activation was evaluated by enzyme-linked
      immunosorbent assay (ELISA)-like microwell colorimetric transcription factor
      activity assay (Trans-AM) and western blot analysis. The radical-scavenging
      activity was determined using the induction period method in the methyl
      methacrylate-azobisisobutyronitrile (AIBN) polymerization system under nearly
      anaerobic conditions. The phenolic bond dissociation enthalpy (BDE) and orbital
      energy were calculated at the density functional theory (DFT) B3LYP/6-31G* level.
      RESULTS: The cytotoxicity against RAW264.7 cells declined in the order bis
      eugenol>eugenol> honokiol>magnolol, whereas the radical-scavenging activity
      declined in the order honokiol, bis-eugenol>magnolol> eugenol. Magnolol and
      honokiol significantly inhibited the fimbria-induced expression of COX-2 at non
      cytotoxic concentrations. Both the fimbria-stimulated binding of NF-kappaB to its
      consensus sequence and phosphorylation-dependent proteolysis of inhibitor kappaB
      alpha were markedly inhibited by magnilol and honokiol, whereas eugenol and bis
      eugenol did not inhibit COX-2 expression and NF-kappaB activation. Magnolol and
      honokiol possessed a high electronegativity (chi) value. CONCLUSION: Magnolol and
      honokiol exhibit antioxidative activity, low cytotoxicity, and anti-inflammatory
      activity. These compounds may be capable of preventing chronic inflammatory
      diseases induced by oral bacteria.

PMID- 23160677
TI  - Variations in the expression and distribution pattern of AQP5 in acinar cells of
      patients with sialadenosis.
AB  - Previously, we pointed out on a possible role of aquaporin 5 (AQP5) in the
      development of sialadenosis. The goal of the present study was to further assess
      the association of AQP5 in the development of this salivary gland disease. The
      acinar diameter and mean surface area appeared elevated in sialadenosis tissues,
      which is a typical observation in this disease. AQP5 expression was evaluated by
      immunohistochemistry using tissue samples derived from salivary glands of
      patients with confirmed sialadenosis either as a primary diagnosis or as a
      secondary diagnosis within the framework of other salivary gland diseases. Normal
      salivary gland tissue served as a control. In sialadenosis tissues, the AQP5
      signal at the apical plasma membrane of acinar cells frequently appeared stronger
      compared with that in normal salivary glands. In addition, the distribution of
      AQP5 at the apical region seemed to differ between normal and sialadenosis
      tissues, where AQP5 frequently was diffusely distributed near or at the apical
      plasma membrane of the acinar cells in contrast to normal controls where the AQP5
      signal was strictly confined to the apical plasma membrane. These observations
      suggest that sialadenosis is associated with a different AQP5 expression and
      distribution pattern in salivary acinar cells.

PMID- 23160678
TI  - Pilot clinical study of Sasa senanensis Rehder leaf extract treatment on
      lichenoid dysplasia.
AB  - BACKGROUND: Previous studies have shown antiviral, antibacterial, and anti
      inflammatory activity of alkaline extract of the leaves of Sasa senanensis Rehder
      (SE). Here, we investigated whether SE is effective on oral lichenoid dysplasia
      and osteoclastogenesis. MATERIALS AND METHODS: A male patient with white lacy
      streaks in the oral mucosa was orally administered SE three times a day for 11
      months. The area of white streaks was monitored by intraoral photography.
      Interleukin-6 and -8 in the saliva were determined by enzyme-linked immunosorbent
      assay. Osteoclastogenesis of mouse macrophage-like RAW264.7 cells, induced by
      receptor activator of nuclear factor-kappaB ligand (RANKL) was monitored by
      tartrate-resistant acid phosphatase (TRAP)-positive multinuclear cell formation.
      RESULTS: Long-term treatment with SE progressively reduced both the area of white
      steaks and the levels of salivary interleukin-6 and -8. SE significantly
      inhibited the macrophage differentiation towards osteoclasts. CONCLUSION: The
      present study suggests the therapeutic potential of SE towards oral diseases.

PMID- 23160679
TI  - Amentoflavone induces cell-cycle arrest and apoptosis in MCF-7 human breast
      cancer cells via mitochondria-dependent pathway.
AB  - Amentoflavone, isolated from an ethyl acetate extract of the whole plant of
      Selaginella tamariscina, a traditional herb, may exhibit antitumor activity. The
      aim of this study was to investigate the anticancer mechanism(s) of
      amentoflavone, such as mitochondria-mediated apoptotic cell death, in typical
      breast cancer MCF-7 cells. Cells treated with amentoflavone exhibited a series of
      cellular alterations related to apoptosis, including DNA and nuclear
      fragmentation, and de-regulation of intracellular reactive oxygen species (ROS)
      and calcium. In addition, markers of mitochondrial-mediated apoptosis, including
      the reduction of mitochondrial inner-membrane potential, the release of
      cytochrome c from mitochondria, and activation of caspase 3, were observed. In
      conclusion, our results present, to our knowledge, the first evidence that
      amentoflavone induces apoptosis of MCF-7 breast cancer cells, and that this is
      closely related to mitochondrial dysfunction. Amentoflavone may be a potential
      therapeutic agent for breast cancer treatment.

PMID- 23160680
TI  - Chlorogenic acid induces apoptotic cell death in U937 leukemia cells through
      caspase- and mitochondria-dependent pathways.
AB  - Chlorogenic acid exists widely in edible and medicinal plants and acts as an
      antioxidant. It is known to exert antitumor activity via induction of apoptosis
      in many human cancer cells. However, its signaling pathway in human leukemia
      cells still remains unclear. Therefore, we investigated the roles of reactive
      oxygen species (ROS), mitochondria and caspases during chlorogenic acid-induced
      apoptosis of U937 human leukemia cells. Chlorogenic acid exhibited a strong
      cytotoxicity and induced apoptosis in U937 cells, as determined by 4,6-diamidino
      2-phenylindole dihydrochloride (DAPI) staining and terminal deoxynucleotidyl
      transferase dUTP nick-end labeling (TUNEL) assay. Chlorogenic acid induced
      apoptosis by promoting ROS production and reduced the mitochondrial membrane
      potential (DeltaPsim), as assayed by flow cytometry. Furthermore, the activity of
      caspase-3 was evaluated and results indicated that chlorogenic acid promoted
      caspase-3 activity in U937 cells. Results from western blot analysis showed that
      chlorogenic acid promoted expression of caspase-3, -7, -8 and -9 in U937 cells.
      Taken together, these results suggest that chlorogenic acid may induce apoptosis
      by reducing the levels of DeltaPsim and by increasing the activation of caspase-3
      pathways in human leukemia U937 cells in vitro.

PMID- 23160681
TI  - Detection of invasive fungal pathogens by real-time PCR and high-resolution
      melting analysis.
AB  - BACKGROUND/AIM: Causative agents most frequently encountered in systemic
      infections are bacteria, although fungi that cause invasive infections have also
      emerged, mostly in immune-compromised patients. The early detection and adequate
      treatment of bloodstream infections are critical for successful treatment. The
      aim of this study was to develop a rapid and efficient method for the detection
      and differentiation of the most common fungal pathogens. MATERIALS AND METHODS:
      Real-time Polymerase chain reaction (PCR) and consecutive high-resolution melting
      analysis was used for the detection and differentiation of fungal pathogens.
      RESULTS: The developed analysis procedure proved appropriate for discrimination
      of the ten most relevant Candida species, four Aspergillus species, and
      Cryptococcus neoformans. The sensitivity of the PCR reaction was 5, which is
      suitable for the detection of these fungi in blood. CONCLUSION: This technique is
      not adaptable as a general identification method, but it is highly useful when
      certain fungal species are to be expected in clinical samples.

PMID- 23160682
TI  - Immunohistological characterization of thymic dendritic cells.
AB  - BACKGROUND: Dendritic cells play key roles in thymic histophysiology and
      histopathology. Therefore, we analyzed the immunotopographical distribution of
      cells expressing markers of dendritic cells and macrophages in postnatal human
      thymus. MATERIALS AND METHODS: The streptavidin-biotin peroxidise-labeled (LSAB)
      and the double-LSAB/alkaline phosphatase/anti-alkaline phosphatase (APAAP)
      immunohistochemical procedures were used. RESULTS: S100 protein-, Cluster of
      designation 1a (CD1a)-, CD207-, CD11c- and CD123-positive cells, many of them
      exhibiting the morphology of dendritic cells, were detected in the cortex but
      mainly in the medulla. These markers, except CD123, were also detected in cells
      of juvenile and immature Hassall bodies. CD68- and CD163-positive cells were
      detected in the cortex and the medulla but not in Hassall bodies. CONCLUSION: The
      immunohistological detection of S100-, CD1a-, CD207- and CD11c-positive dendritic
      cells in juvenile and immature Hassall bodies may reflect an important role of
      these structures in the cooperation of epithelial and dendritic cells in the
      process of T-cell differentiation.

PMID- 23160683
TI  - In search of new biological activities of isolates from Odontoglossum
      Harvengtense 'Tutu'.
AB  - BACKGROUND: In the current study, we isolated four known compounds, two
      phenanthrenes, 2,5-dihydroxy-4,9-dimethoxy phenanthrene [1] and 4
      methoxyphenanthrene-2,7-diol (flavanthrinin) [2], one phenanthrenequinone, 5
      hydroxy-2,3-dimethoxy-1,4-phenanthrenequinone [3], and one flavone, 3,5,7
      trihydroxyflavone (galangin) [4], from the ethyl acetate (EtOAc) extract of
      Odontoglossum Harvengtense 'Tutu' through bioassay-guided fractionation, and
      investigated their biological activities. MATERIALS AND METHODS: The isolated
      compounds were identified with spectroscopic analysis and through comparison to
      literature values. Cytotoxic activity towards human tumor and normal cells was
      determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide
      (MTT) method. Nitric oxide (NO) was determined by the Griess method. Radical
      scavenging activity was determined by electron spin resonance (ESR) spectroscopy.
      Osteoclastogenesis was monitored by tartrate-resistant acid phosphatase (TRAP)
      activity. RESULTS: The compounds had slightly higher cytotoxicity towards human
      oral squamous cell carcinoma and leukemia cell lines as compared with human
      normal oral cells, yielding a tumor specificity value of 1.1-2.7. Among these
      four compounds, 1 most potently inhibited the lipopolysaccharide (LPS)-stimulated
      NO production and the receptor activator of nuclear factor-kappaB ligand (RANKL)
      stimulated osteoclastogenesis by mouse macrophage-like RAW264.7 cells. Micromolar
      concentrations of 1 scavenged the NO radical produced from 1-hydroxy-2-oxo-3-(N-3
      methyl-3-aminopropyl)-3-methyl-1-triazene. CONCLUSION: The present study
      demonstrated, for the first time, that 1 inhibited both macrophage activation and
      osteoclast differentiation, suggesting its possible anti-inflammatory action.

PMID- 23160684
TI  - Oral carcinogenesis is not achieved in different carcinogen-treated PAI-1
      transgenic and wild-type mouse models.
AB  - AIM: In an effort to assess the role of plasminogen activator inhibitor-1 (PAI-1)
      in oral squamous cancer development and progression, two different carcinogen
      treatment protocols were conducted. MATERIALS AND METHODS: Protocol I included
      mice from a PAI-1 transgenic (Tg) breed (n=56) and their wild-type (WT)
      counterparts (n=56), divided into one control group and two main experimental
      groups, treated with 7,12-dimethylbenz[a]anthracene (DMBA) for 8 and 16 weeks,
      respectively. Protocol II included the same number and types of animals and
      groups, which were similarly treated with 4-Nitroquinoline 1-oxide (4-NQO) in
      drinking water. Two drugs that affect plasma PAI-1 levels, enalapril and
      pravastatin, were administered to certain subgroups of animals in both protocols.
      RESULTS: None of the animals developed macroscopically-visible oral cancer
      lesions. Eleven animals under Protocol I and 52 animals under Protocol II died.
      Skin lesions were noted only in DMBA-treated animals (n=9). Almost all animals
      administered with 4-NQO developed alopecia and lost weight, while two of them
      developed stomach tumours, and one female mouse developed a large ovarian cyst.
      CONCLUSION: Transgenic mice may respond differently when used in well-established
      carcinogen models and oral carcinogenesis is hard to achieve in these rodents.

PMID- 23160685
TI  - Anti-UV/HIV activity of Kampo medicines and constituent plant extracts.
AB  - AIM: In order to search for new biological activities of Kampo medicines and
      their constituent plant extracts, we investigated whether they protect the cells
      from the cytotoxicity induced by UV irradiation and human immunodeficiency virus
      (HIV) infection. MATERIALS AND METHODS: Anti-UV/HIV activity (SI value) was
      evaluated as the ratio of the CC(50) (concentration that reduced the viable cell
      number by 50%) to the EC(50) (the concentration that increased the viability of
      UV-irradiated or HIV-infected cells to 50%): SI=CC(50)/EC(50). The content of
      glycyrrhizin in each sample was determined by high performance liquid
      chromatography (HPLC). Caspase-3/-7 activity was assayed by cleavage of poly ADP
      ribose polymerase using western blot analysis. RESULTS: Among 25 plant extracts,
      Gardenia fruit had the highest anti-UV activity (SI>=8.0), followed by
      Glycyrrhiza (SI=4.3), Coptis rhizoma (SI=1.5), Cimicifuga rhizoma (SI>1.4),
      Saposhnikovia root (SI>1.3) and Japanese Gentian (SI>1.1). Among ten Kampo
      medicines, Unseiin and Hangesyashinto (SI>4.9) had the highest anti-UV activity,
      followed by Shosaikoto (SI>4.3), Saireito (SI>3.4), Rikkosan (SI>1.2) and Kikyoto
      (SI=1.1). Glycyrrhiza inhibited UV-induced caspase-3/-7 activation. Only
      Polyporus sclerotium (SI>4.4), Gardenia fruit (SI>2.7), Atractylodes lancea
      rhizoma (SI>1.9), Cnidium rhizoma (SI>1.5) and Japanese Angelica root (SI>1.1)
      exhibited some anti-HIV activity. There was no apparent correlation of their anti
      UV/HIV activity and content of glycyrrhizin, a major component of Glycyrrhiza,
      which exhibited much higher anti-UV activity (SI=20.6) and some anti-HIV activity
      (SI>2.0). CONCLUSION: The present study suggests the involvement of substances
      other than glycyrrhizin in the anti-UV/HIV activity of Kampo medicines and their
      constituent plant extracts.

PMID- 23160686
TI  - Pilot study of changes in salivary metabolic profiles induced by template
      therapy.
AB  - BACKGROUND: Occlusal raising method (so-called 'Template therapy') has been
      reported to alleviate various diseases and symptoms, but the underlying mechanism
      is not clear. We searched the low-molecular weight metabolite(s) in the saliva,
      the concentration of which is significantly changed by the template therapy.
      MATERIALS AND METHODS: One female patient with headache underwent the template
      therapy for 12 days, and her total saliva was subjected to non-targeted analysis
      using capillary electrophoresis time-of-flight mass spectrometry (CE-TOF-MS).
      RESULTS: One hundred and thirteen substances were identified in the saliva.
      Glycine was the most abundant amino acid in the saliva, followed by alanine,
      serine and proline. After the start of the template therapy, her headache was
      alleviated, accompanied by a significant (p=0.042) increase of salivary
      concentration of glycine, as compared with total amino acids whereas that of
      other amino acids was not significantly changed. In the metabolomics profile,
      salivary concentration of large number of metabolites as compared with total
      metabolite concentration decreased, including N-acetylneuraminate (p=0.025) and p
      hydroxyphenylacetate (p=0.039). CONCLUSION: This pilot study demonstrated, to our
      knowledge for the first time, that only glycine exhibited unique changes among
      total metabolites, suggesting its significant role in template therapy.

PMID- 23160687
TI  - Factors involved in sudden coagulation observed in patients with acute myocardial
      infarction.
AB  - Coronary artery diseases (CAD) evolving into acute myocardial infarction (AMI) is
      associated with coagulation and thrombotic occlusion of coronary vessels in the
      presence of unstable atheroma. The atheromatous plaque becomes unstable when it
      is infiltrated by monocytes, macrophages and neutrophils capable of secreting
      proteases that induce plaque erosion, rupture and initialize the coagulation
      process. The aim of this study was (a) to analyse the plasma of patients with AMI
      for the presence of proteases that may activate rapid coagulation, (b) to
      evaluate coagulation markers as prothrombin fragment (F1+2) and antithrombin III
      and (c) to find an interrelation between proteases and coagulation markers. The
      examined plasma showed high values of prothrombin fragment (F1+2) and low levels
      of antithrombin III. These markers showed a highly significant negative
      correlation. The plasma also exhibited increased levels of matrix
      metalloproteinase-9 (MMP-9) which were positively-correlated with the prothrombin
      fragment (F1+2). MMP-9 seems to cause the coagulation activity by increasing the
      level of prothrombin fragment (F1+2) and the consumption of antithrombin III. The
      examined plasma also exhibited high levels of neutrophil gelatinase-associated
      lipocalin (NGAL), which is known to modulate MMP-9 activity. The high plasma
      levels of MMP-9 and NGAL can be attributed to plaque instability and appear to
      activate sudden coagulation. MMP-9 and NGAL, in the presence of altered values of
      prothrombin fragment (F1+2) and antithrombin III in AMI patients, seem to be
      suitable markers to be studied in unstable plaque patients, for the prediction
      and prevention of acute coronary syndrome.

PMID- 23160688
TI  - Evaluation of aortic valve stenosis using a hybrid approach of Doppler
      echocardiography and inert gas rebreathing.
AB  - BACKGROUND: Doppler echocardiography is the method of choice for diagnosis and
      evaluation of aortic stenosis. However, there are well-known limitations to this
      method in difficult-to-image patients. Flow acceleration in the left ventricular
      outflow tract (LVOT) can lead to overestimation of stroke volume (SV) and poor
      acoustic windows may impede the exact measurement of the LVOT. The present study
      aimed to evaluate the use of inert gas rebreathing (IGR)-derived SV in this
      situation. PATIENTS AND METHODS: We replaced Doppler-derived SV measurements in
      the continuity equation (method A) by SV determined by IGR (method B) and by
      thermodilution during right heart catheterization (method C) to calculate the
      aortic valve area (AVA) in 21 consecutive patients with moderate or severe aortic
      stenosis. RESULTS: Mean SV and AVA did not differ between methods at 72+/-21 ml
      and 0.71+/-0.2 cm(2) (method A) vs. 66+/-18 ml and 0.67+/-0.21 cm(2) (method B)
      vs. 64+/-15 ml and 0.67+/-0.21 cm(2) (method C), respectively (all p-values
      >0.05). The mean difference and limits of agreement for AVA were 0.04+/-0.23
      cm(2) and -0.40 to 0.47 cm(2) between methods A and B, 0.05+/-0.14 cm(2) and 
      0.26 to 0.27 cm(2) between A and C, and -0.05+/-0.23 cm(2) and -0.45 to 0.35
      cm(2) between B and C, respectively (all p-values >0.05). CONCLUSION: The
      presented approach is a reliable method for the calculation of AVA and can add a
      diagnostic option for the use in difficult-to-image patients. Whereas the use of
      thermodilution is limited due to its invasive nature, IGR allows the fast and non
      invasive determination of cardiac function at low cost.

PMID- 23160689
TI  - Cardiac computed tomographic angiography in patients with acute chest pain and
      moderately-increased troponin.
AB  - AIM: The aim of the study was to investigate patients with undefined chest pain
      and moderately increased troponin based on the results of cardiac computed
      tomographic (CT) angiography (CCTA). PATIENTS AND METHODS: We analysed the cases
      of 43 patients with acute chest pain and moderately increased troponin in whom
      CCTA was performed. Patients with suspected stenosis on CCTA underwent
      percutaneous coronary angiography (PCA). RESULTS: CCTA ruled-out significant
      coronary stenosis in 32 patients. Eleven patients had suspected significant
      coronary stenosis on CCTA. Ten patients underwent PCA, which verified significant
      coronary lesions in nine. Out of these, four patients were treated by
      percutaneous coronary intervention (PCI). One patient had to undergo coronary
      artery bypass grafting. A triple-rule-out CT protocol was performed in 18
      patients, demonstrating pulmonary embolism in three and pericardial effusion of
      unknown origin in two. CONCLUSION: CCTA accurately identifies or rules out
      patients with undefined chest pain and moderately elevated troponin, which
      require PCA and allows detection of other significant clinical findings.

PMID- 23160690
TI  - Relationship between bone formation markers bone alkaline phosphatase,
      osteocalcin and amino-terminal propeptide of type I collagen and bone mineral
      density in elderly men. Preliminary results.
AB  - Bone remodeling is altered in all metabolic bone diseases, especially in post
      menopausal women and in the elderly. Predicting changes in bone mineral density
      (BMD) is useful to manage the progression of such diseases and to potentially
      provide interventions in reducing fracture risk. Continuous bone formation and
      resorption processes can be monitored by measuring biochemical markers of bone
      turnover (BTMs) and a relationship between BMD and BTMs has been known for long.
      The aim of this study was to evaluate the relationship between BMD and serum BTMs
      bone alkaline phosphatase (BAP), osteocalcin and amino-terminal propeptide of
      type I collegen (PINP) in elderly (>65 years) men. We prospectively studied 18
      elderly men (median age=69, range=65-77 years) with no history of fractures,
      angina, stroke, myocardial infarction or diabetes mellitus. Patients who had
      undergone corticosteroid, calcitonin, androgen or bisphosphonate therapy were
      excluded from the study, as well as those who were vitamin D and calcium
      supplementation users. All the patients underwent lumbar-spine (L2-L4) dual
      energy x-ray absorbtiometry and BMD, BAP, osteocalcin and PINP measurements. The
      mean BMD and body mass index (BMI) were 0.963+/-0.04 g/cm(2) and 24.4+/-1.2
      kg/m(2), respectively. BAP, osteocalcin and PINP were 27.8+/-11.3 U/l, 25.6+/-7.1
      ng/ml and 36.0+/-7.5 ng/ml, respectively. No correlation was found between BMD
      and BAP (R=-0.28, p=0.25), osteocalcin (R=-0.18, p=0.48) and PINP (R=-0.21,
      p=0.39), nor between BMI and both age (R=0.05, p=0.83) and BMD (R=0.10, p=0.67).
      In conclusion, we did not find any relationship between bone formation markers
      BAP, osteocalcin and PINP and bone density. Thus, our preliminary data suggest
      that BTMs are not useful in monitoring the bone mineral status of elderly men.

PMID- 23160691
TI  - An unilateral basal bone defect of the mandible occupied by fatty tissue:
      Stafne's cavity.
AB  - The differential diagnosis of osseous jaw lesions includes numerous entities. A
      specific mandibular bone defect known as Stafne's cavity or cyst presents wirh a
      characteristic cyst-like lesion on radiographs of the jaw. Although the
      differential diagnosis from other jaw lesions is mandatory, this lesion does not
      usually require surgical therapy. Current theories concerning the pathogenesis of
      Stafne's cavity prefer bone depression as a consequence of constant pressure
      arising from an adjacent salivary gland. We present a case of a large Stafne's
      cavity eroding the basal mandibular cortex that was found accidentally on an
      orthopantogram taken for diagnosis of dental diseases. The patient noted a slight
      pain on pressure during physical investigation. The lesion was completely
      occupied by fatty tissue, as shown during surgical exploration and as revealed by
      histological investigation of the specimen. The theory of parenchymal pressure as
      the cause of mandibular bone depression appears to be inapplicable in the present
      case. The pathogenesis of Stafne's cavity is still obscure. Differential
      diagnosis of mandibular lesions is essential in adequate treatment planning.

PMID- 23160692
TI  - Incidentally discovered asymptomatic splenic hamartoma with rapidly expansive
      growth: a case report.
AB  - Splenic hamartoma (SH) is a very rare benign vascular lesion, usually
      asymptomatic. Although infrequent, it must be differentiated from malignant
      lesions, such as lymphoma or metastases, or other vascular neoplasms of the
      spleen. We present the case of a solid lesion of the spleen discovered
      incidentally in a 42-year-ol women, characterized by an unusual rapid expansive
      growth during four-month follow-up. The lesion, isoechoic and close to the hilum,
      was initially suspected to be an accessory spleen, measuring 3.5 cm in size. Four
      months later, magnetic resonance imaging revealed a 9-cm expansive nonhomogeneous
      mass in the antero-superior margin of the spleen, dislocating the stomach. The
      lesion exhibited central necrosis with hyper- and hypointense signal both in T1
      and T2-weighted images. Due to the risk of spontaneous rupture and because
      malignancy could not be ruled out, the patient underwent hand-assisted
      laparoscopic splenectomy. Macroscopically, the spleen measured 15*12*4 cm and
      weighed 890 g. Cut sections revealed a single nodule of dark-red tissue sized 8.5
      cm. The lesion exhibited a network of irregularly arranged and tortuous vascular
      channels lined by endothelium similar to splenic sinus lining cells, surrounded
      by aggregates of lymphocytes and macrophages resembling the pulp cords. On
      immunohistochemical staining the tissue was CD34 - and CD8 + and the final
      diagnosis was SH. In conclusion, when SH is suspected and malignancy cannot be
      ruled out, hand-assisted splenectomy should be considered the procedure of
      choice. Partial splenectomy should be preferred in children, to avoid potential
      risks of total splenectomy.

PMID- 23160693
TI  - A case of hydroxyurea-induced leg ulcer after definitive treatment suspension in
      a patient affected by thrombocythemia: effectiveness of a new collagenase.
AB  - Hydroxyurea (HU) is an antitumor agent effective in the treatment of
      myeloproliferative disorders. It is usually well-tolerated and has low toxicity
      but its use is associated with several adverse cutaneous effects. Among them, leg
      ulcers have been noted in association with long-term administration. Poor
      response to traditional local and systemic therapy is a typical feature of HU
      induced leg ulcers, and discontinuation of the drug is often required to achieve
      complete wound healing. We present a case of circumferential HU-induced leg ulcer
      in a patient affected by essential thrombocythemia, in which the lesion occured
      after the definitive suspension of the treatment. We propose a conservative
      management with a new collagenase (Bionect Start(r)) for skin lesions in this
      type of patient, for whom a surgical treatment could be more complicated, due to
      the underlying disease.

PMID- 23160694
TI  - Predictive role of thymidine phosphorylase expression in patients with colorectal
      cancer and its association with angiogenesis-related proteins and extracellular
      matrix components.
AB  - BACKGROUND: Thymidine phosphorylase (TYMP) is an angiogenic factor that has
      potent chemotactic activity for endothelial cells and is involved in 5
      fluorouracil (5-FU) metabolism. In colorectal cancer (CRC), previous studies
      evaluating the relationship between TYMP expression and clinicopathological
      features have yielded inconsistent results. The aim of this study was to
      investigate the prognostic value of TYMP, its association with other angiogenic
      factors, proliferation markers and, to our knowledge, for the first time its
      relationship with extracellular matrix components. MATERIALS AND METHODS:
      Formalin-fixed, paraffin-embedded specimens from 97 patients with CRC were
      immunostained for TYMP, vascular endothelial growth factor (VEGF), microvascular
      density (CD34), proliferation marker (Ki-67), proliferating cell nuclear antigen
      (PCNA), p53 oncoprotein and extracellular matrix components (collagen type IV,
      fibronectin, tenascin and laminin). Survival curves were calculated with the
      Kaplan-Meier method. RESULTS: Immunoreactivity was observed in the cytoplasm
      (cyt) and nucleus (n) of the tumor cells, as well in the stroma (st), endothelium
      and tumor-associated macrophages. High TYMPcyt expression was observed in 7.2% of
      the cases, moderate in 22.7% and weak in 59.9%, while 10.3% were negative. High
      TYMPst expression was observed in 58.8% of the cases. TYMPcyt expression was
      correlated with the VEGF expression of tumor cells and VEGF expression of vessels
      (p=0.014 and p=0.022, respectively). TYMPst expression was correlated with VEGF
      expression and tenascin (p=0.014 and p=0.011, respectively). Patients with higher
      TYMPcyt expression had a more favorable overall survival (p=0.041) in univariate
      analysis compared to patients without TYMP expression. CONCLUSION: These findings
      suggest that TYMP plays an important role in angiogenesis, extracellular matrix
      remodeling and in the prognosis of patients with CRC, but further studies are
      needed to clearly define its role in CRC.

PMID- 23160695
TI  - Influence of overweight in elderly patients undergoing vaginal surgery due to
      pelvic floor disorders.
AB  - AIM: To evaluate the feasibility and safety of vaginal surgery for treatment of
      genital prolapse in overweight compared to normal weight patients aged 50 years
      or older. PATIENTS AND METHODS: We retrospectively reviewed the perioperative
      data of 93 patients aged between 50 and 87 years undergoing surgery due to pelvic
      floor disorders. A total of 54 women had a body mass index (BMI) of 25 kg/m(2) or
      higher and were defined as the study collective. Thirty-nine patients undergoing
      similar surgical procedures during the same period of time had a BMI less than 25
      kg/m(2) and served as the control group. Operating time, duration of hospital
      stay, intra- and postoperative complications were evaluated as comorbidities.
      chi(2)-test, Fisher's exact test, Student's t-test and non-parametric Mann
      Whitney U-test were applied to compare the results of both collectives. RESULTS:
      There were no significant differences between study and control collectives
      regarding time of surgery, duration of hospital stay or intra- and postoperative
      complications, although a significant difference was found with regard to the
      prevalence of pre-existing diabetes mellitus (17% in the study group, versus 5%
      in the control group, respectively, Fisher's exact test: p=0.04). CONCLUSION:
      Overweight in elderly patients undergoing vaginal surgery due to pelvic floor
      disorders does not affect the perioperative outcome and is not a risk factor for
      perioperative complications.

PMID- 23160696
TI  - Ropivacaine versus levobupivacaine for minor breast surgery in outpatients:
      inversion of postoperative pain relief efficacy.
AB  - The number of ambulatory surgical procedures is growing and local anesthesia
      represents the technique of choice for outpatients undergoing minor surgery. The
      aim of this study was to verify whether differences exist in postoperative pain
      relief using equipotent doses of two long-acting local anesthetics, ropivacaine
      and levobupivacaine, in patients who underwent minor breast surgery. A series of
      86 consecutive women (median age=55, range=39-75 years) with small (<2 cm in
      size) breast masses requiring surgical excision were prospectively enrolled in
      the study. Patients were randomly selected to receive 7.5 mg/ml ropivacaine
      (group A, 42 patients) or 5 mg/ml levobupivacaine (group B, 44 patient). For post
      surgical measurement of pain intensity a visual analog scale (VAS) was used. The
      age of the patients (56.4+/-9.6 vs. 56.7+/-9.5 years; p=0.88) and operative time
      (38.4+/-4.3 vs. 39.8+/-5.0 min; p=0.16), did not differ significantly between the
      groups (A vs. B). Transient adverse effects were observed in 5 (11.9%) and 4
      (9.1%) patients (p=0.49) of groups A and B, respectively. The pain VAS four (t4)
      and 24 (t24) hours from the end of surgery was significantly (p<0.05) different
      between the groups, but an inversion of pain relief efficacy and a crossing point
      of the two pain-time lines at the sixth hour was observed. In conclusion,
      ropivacaine results in more effective pain relief at time t4, while
      levobupivacaine should be the drug of choice when long-term postoperative
      analgesia is required.

PMID- 23160697
TI  - Leptomeningeal metastasis in melanoma: a prospective clinical study of nine
      patients.
AB  - BACKGROUND: Melanoma has the highest rate of spread to the leptomeninges and the
      incidence of melanoma has been steadily rising. This article describes recent
      experience at the Lille University Hospital, between 2007 and 2011 and discusses
      the possibilities for treatment of leptomeningeal metastasis. PATIENTS AND
      METHODS: Nine patients were diagnosed with leptomeningeal metastasis of melanoma.
      The standard criteria were used for the diagnosis. The treatment consisted of a
      combination of intrathecal chemotherapy, systemic chemotherapy and best
      supportive care. RESULTS: The overall median survival from the time of
      leptomeningeal metastasis diagnosis was eight weeks (range=1-168 weeks). In two
      cases, the median overall survival was 104 weeks. For these patients, there was a
      clear benefit in intrathecal chemotherapy combined with systemic treatment. No
      complication was observed. CONCLUSION: Despite a poor prognosis, treatment of
      melanoma leptomeningeal metastasis is needed in order to improve the quality of
      life, neurological progression-free survival and overall survival of patients.

PMID- 23160698
TI  - Intraoral lymphoepithelial carcinoma of the minor salivary glands.
AB  - The occurrence of lymphoepithelial carcinoma in the oral cavity is extremely rare
      and a case with involvement of minor salivary glands is very uncommon. We
      describe a case of LELC of the oral cavity with involvement of the upper lip and
      of minor salivary glands. The tumour was described at the clinical and
      instrumental level; moreover, its histopathological phenotype was defined.
      Finally, the problems of differential diagnosis and the most appropriate
      therapeutic approaches are discussed.

PMID- 23160699
TI  - Subcutaneous angioleiomyoma of the nasal tip. Report of a rare case.
AB  - Angioleiomyoma is a rare benign tumor of smooth muscle origin. It has been
      reported in many anatomical sites, but it is very rare in the nose. This article
      describes the case of a 46-year-old woman, with a subcutaneous vascular leiomyoma
      of the nasal tip. She reported a small painless mass. The skin which was covering
      it became strongly erythematous at high temperatures, with an annoying increase
      of the sensitivity. There are no specific imaging techniques capable of
      characterizing the vascular leiomyoma, however sonography represents an excellent
      modality for initial evaluation of this kind of lesion. We chose excision with an
      open rhinoplasty approach for treatment of the lesion. Obvious and disfiguring
      scars do not remain with this surgical approach. The patient had immediate and
      complete relief of her symptoms, the aesthetic result is very good and her
      satisfaction is complete.

PMID- 23160700
TI  - Prevalence of thrombosis-related DNA polymorphisms in a healthy Greek population.
AB  - Genetic association studies have revealed a correlation between DNA variations in
      genes encoding factors of the haemostatic system and thrombosis-related disease.
      This study investigated the prevalence of 13 such genetic risk factors in a
      sample (N=400 alleles) of the Hellenic population of Greece. Some of these
      polymorphisms [coagulation factor V (F5) Leiden, coagulation factor II (F2)
      G20210A, 5,10-methylene tetrahydrofolate reductase (MTHFR) C677T, coagulation
      factor XIII A1 subunit (F13A1) Val34Leu, serpine1 (SERPINE1) 4G/5G, angiotensin I
      converting enzyme (ACE) I/D, angiotensinogen (AGT) Met325Thr, integrin A2 (ITGA2)
      C807T] have been previously studied in Hellenic populations of Greece and Cyprus,
      while others such as coagulation factor XII (F12) C46T, plasma carboxypeptidase
      B2 (CPB2) C1040T, platelet glycoprotein Ib alpha polypeptide (GP1BA) VNTR,
      thrombomodulin (THBD) -A33G and protein Z (PROZ) - A13G have not. Most of the
      allelic frequencies observed are similar to those reported for other Southern
      European populations. Knowledge of the prevalence of these variations in a given
      population may assist in the design of effective preventive measures against
      cardiovascular disease.

PMID- 23160701
TI  - Anterior lingual mandibular bone depression in an 11-year-old child.
AB  - This report describes physical and imaging findings in a case of anterior lingual
      mandibular bone depression in a child. This entity is very rarely diagnosed and
      even more extremely rarely seen in children. We present some characteristic
      findings depicted on images provided by different sources and briefly address
      current hypotheses on its pathogenesis.

PMID- 23160703
TI  - Impact of stroke-associated infection on long-term survival: a cohort study.
AB  - BACKGROUND AND OBJECTIVE: The effects of stroke-associated infection (SAI) on
      long-term survival are unclear. We performed a prospective evaluation to explore
      risk factors of SAI, and compared survival status over the 3 years following
      stroke onset between those who experienced SAI and those who did not. METHODS:
      Consecutive patients with acute stroke admitted to a stroke unit between April
      2005 and December 2006 were invited to participate. We prospectively collected
      data on demographics, pathological and clinical stroke subtype, stroke severity,
      and neurological and functional consequences, and abstracted additional data on
      occurrence and timing of SAI in hospital from medical notes. Survival status 3
      years after stroke onset was obtained. RESULTS: We recruited 413 acute stroke
      patients, 161 (39%) experienced SAI. After excluding patients with infection at
      onset, patients with intracerebral haemorrhage (p=0.014), dysphagia (p=0.003) and
      urinary incontinence/catheterisation (p=0.000) were at higher risk of infection
      after controlling for case mix. The risk of death in hospital was greater
      following an SAI (HR 3.56; 95% CI 1.94 to 6.53; p=0.000), as was risk of death
      calculated over the whole 3-year follow-up period among those acquiring SAI
      within 2 weeks of onset (HR 1.66; 95% CI 1.14 to 2.40; p=0.031). CONCLUSIONS:
      SAIs have long-lasting effects on patient survival. This serves to emphasise the
      importance of immediate access to organised stroke unit care for people with
      acute stroke, with active physiological monitoring and protocols for early
      detection and treatment of SAIs.

PMID- 23160704
TI  - Unity of opposites? Chronic fatigue syndrome and the challenge of divergent
      perspectives in guideline development.
AB  - Guideline development by its nature is a process and method of integration and
      synthesis of information, be it originating from research, evidence-based
      medicine, clinical findings, patient experience and/or individual narratives of
      an illness or disease. In the majority of cases, it can be assumed that this
      information and these ideas are travelling in the same direction; however, it is
      possible that the objective and subjective cannot be synthesised, and appear
      mutually contradictory. In this commentary, an example of where this might be the
      case has been analysed: a report published by the Scottish Public Health Network,
      a Health Care Needs Assessment of Services for people living with myalgic
      encephalomyelitis (ME)/chronic fatigue syndrome (CFS). It appears from reflection
      and analysis of this document that this process may indeed have gone awry. We
      propose that, if followed, this document would lead to the adoption of dangerous
      diagnostic criteria for ME/CFS, as well as preventing patients from making
      informed decisions about treatment options, and discouraging clinicians from
      following evidence-based medicine and recommending proven treatments for ME/CFS,
      because of potential implications for future commissioning. This commentary seeks
      to highlight some of the problems, contradictions and unintended consequences of
      a divergence between patient perspectives and evidence-based medicine despite
      probably sharing the same aim, that of improving patient care and striving for
      better understanding and better treatments for disease. 

PMID- 23160705
TI  - Alteration of cell responses to PrP(Sc) in prolonged cell culture and its effect
      on transmission of PrP(Sc) to neural cells.
AB  - The mechanisms and processes of the uptake, intracellular trafficking and
      intercellular spread of PrP(Sc) and its transfer to neural cells are not clearly
      defined. The involvement of immune, intestinal, mast or peripheral neural cells
      in this process also remains unclear. The role of these cell types in the
      accumulation and transfer of PrP(Sc) to neural cells was investigated following
      short and prolonged exposure to the Chandler and Obihiro strains of scrapie
      PrP(Sc) for up to 28 days. Eight cell lines of murine immune, neural, intestinal
      and fibroblast cell types were tested. After transient degradation phases,
      certain immune, intestinal and neural cells accumulated PrP(Sc) for up to 28 days
      postinfection. When co-cultured with N2a-3/EGFP neuroblastoma cells for 4 days
      followed by several passages, the immune, intestinal and the neural cell lines
      were able to transfer infection to neural cells. Our results suggest that some of
      these cell types may have a role in PrP(Sc) accumulation and intercellular spread
      of PrP(Sc) infection to neural cells in vivo.

PMID- 23160706
TI  - Analysis of molecular variation of porcine reproductive and respiratory syndrome
      virus in Central China from 2006 to 2012.
AB  - To analyze the epidemiology of PRRSV in Hubei Province of China, 668 serum
      samples collected from 14 pig-breeding farms were tested. We found that the PRRSV
      positive rate was 5.24 % and that HP-PRRSV had become the dominant strain. To
      further investigate the genetic variation of PRRSV strains in this region, the
      complete gene sequences of nsp2, orf5, and orf7 from nine PRRSV strains collected
      during 2011-2012 were determined and compared with 33 known sequences. The
      results revealed that diverse HP-PRRSV strains are present in this region. An
      analysis of orf5 gene sequences showed that the strains collected during 2009
      2010 formed a tightly clustered branch. When compared with the JXA1 strain, they
      had one mutation (V29 -> A29) in a decoy epitope. Furthermore, we found that the
      number of potential N-glycosylation sites had apparently increased since 2006.
      These findings increase our knowledge of PRRSV epidemiology in Central China.

PMID- 23160707
TI  - MOFs constructed with the newly designed imidazole dicarboxylate bearing a 2
      position aromatic substituent: hydro(solvo)thermal syntheses, crystal structures
      and properties.
AB  - Six metal-organic frameworks, namely, [Cd(MU(2)-HDMPhIDC)(Py)](n) (H(3)DMPhIDC =
      2-(3,4-dimethylphenyl)-1H-imidazole-4,5-dicarboxylic acid, Py = pyridine) (1),
      [Sr(MU(2)-HDMPhIDC)(H(2)O)](n) (2), {[M1(3)(MU(3)
      DMPhIDC)(2)(H(2)O)(6)].2H(2)O}(n) (M1 = Zn (3), or Mn (4)), [M2(MU(2)
      HDMPhIDC)(H(2)O)(2)](n) (M2 = Mg (5), or Ca (6)), have been hydro(solvo)thermally
      synthesized and structurally characterized by single-crystal X-ray diffraction,
      elemental analyses, X-ray powder diffraction (XRPD), thermal analyses and IR
      spectra. 1 is a meso-compound and displays a 3D non-interpenetrated framework
      with 1D open channels and [Cd(2)(HDMPhIDC)(3)(Py)(2)](4) cages, which are
      composed of left- and right-handed helices pillared by Cd(2+) linkages. Polymer 2
      exhibits a sheet structure containing infinite distorted hexagonal rings
      assembled from adjacent corrugated-shaped polymeric chains. Polymers 3 and 4 are
      isomorphous with an interesting 3D network containing infinite 1D-hexagonal
      channels and [M2(2)(DMPhIDC)](6) cages, which have two interpenetrating net
      topologies. Both polymers 5 and 6 present interesting two-dimensional
      architectures. In these MOFs, the imidazole dicarboxylate ligand shows the
      diversity in its coordination modes and strong coordination ability. There exists
      antiferromagnetic coupling between the Mn(II) ions in 4. Furthermore, the solid
      state luminescent properties for polymers 1-3, 5 and 6 have also been discussed
      in detail.

PMID- 23160708
TI  - Voltage-sensitive chloride ion channels in Anopheles gambiae Sua-1B cells.
AB  - In this study, we performed electrophysiological analysis of Anopheles gambiae
      Sua-1B cells having "neuron-like" morphologies using the patch clamp method. The
      recorded cells (n = 79) had processes resembling axons/dendrites, with 63 %
      unipolar, 22 % bipolar, and 15 % multipolar. While no inward currents were
      observed following step depolarizations (holding potential = -80 mV), a slowly
      activating outward current was observed in 96 % of the cells, especially at
      depolarized potentials. The amplitude of the current was attenuated nearly 70 %
      by reducing extracellular Cl- ion concentration, or by incubating with 100 MUM
      DIDS, a known voltage-sensitive chloride channel blocker, suggesting that the
      current was mediated by chloride ions. No qualitative difference was found
      between recordings made with Cs+ ions in the intracellular pipette solution
      (inhibits K+ currents) and those made with normal physiological solution,
      indicating a deficiency of potassium channels. Additionally, recordings made with
      Ca2+-free extracellular bath solution eliminated the slowly activating outward
      current. A subset of cells (n = 3) lacked this current, but had outward currents
      with voltage-dependent properties similar to those of volume-regulated chloride
      channels. Taken together, our results suggest that the voltage-sensitive currents
      observed in the majority of Sua-1B cells are mediated primarily by chloride
      channels of the calcium-dependent subtype.

PMID- 23160709
TI  - Acute exposure to a sublethal dose of imidacloprid and coumaphos enhances
      olfactory learning and memory in the honeybee Apis mellifera.
AB  - The decline of honeybees and other pollinating insects is a current cause for
      concern. A major factor implicated in their decline is exposure to agricultural
      chemicals, in particular the neonicotinoid insecticides such as imidacloprid.
      Honeybees are also subjected to additional chemical exposure when beekeepers
      treat hives with acaricides to combat the mite Varroa destructor. Here, we assess
      the effects of acute sublethal doses of the neonicotinoid imidacloprid, and the
      organophosphate acaricide coumaphos, on honey bee learning and memory.
      Imidacloprid had little effect on performance in a six-trial olfactory
      conditioning assay, while coumaphos caused a modest impairment. We report a
      surprising lack of additive adverse effects when both compounds were administered
      simultaneously, which instead produced a modest improvement in learning and
      memory.

PMID- 23160710
TI  - Age-specificity and the evolution of senescence: a discussion.
AB  - Senescence evolved because selection pressure declines with age. However, to
      explain senescence it does not suffice to demonstrate that selection pressure
      declines. It is also necessary to postulate biological mechanisms that lead to a
      deteriorated state of the organism at high ages, but not before. This has lead to
      the invocation of 'age-specific' genes or processes, a concept which is prone to
      be interpreted too freely. Events do not happen after a certain amount of time
      has passed. They need initiation, which means that senescence is required to be a
      continuous process. As a result, a change at a particular age cannot arise in
      isolation from changes at other ages, in particular not in isolation from changes
      at the ages nearby. These mechanistic constraints are not without consequence for
      the patterns of mortality and fecundity that can evolve. I conclude that from
      purely logical considerations, senescence is characterized as continuous rather
      than age-specific deterioration. These considerations guide (theoretical)
      research in the direction of investigating how continuous somatic change arises,
      rather than focusing at age-specific events.

PMID- 23160711
TI  - Highly porous metal-organic framework sustained with 12-connected nanoscopic
      octahedra.
AB  - Two dicopper(II)-paddlewheel-based metal-organic frameworks (PCN-81 and -82) have
      been synthesized by using tetratopic ligands featuring 90 degrees -carbazole
      dicarboxylate moieties. Both adopt 12-connected tfb topology with nanoscopic
      octahedra as building units. The freeze-dried PCN-82 shows Brunauer-Emmett-Teller
      (BET) and Langmuir surface areas as high as 4488 and 4859 m(2) g(-1),
      respectively. It also exhibits high H(2)-adsorption capacity at low pressure (300
      cm(3) g(-1) or 2.6 wt% at 77 K and 1 bar), which can be attributed to its high
      surface area, microporosity, and open metal sites.

PMID- 23160712
TI  - Time scales of memory, learning, and plasticity.
AB  - After only about 10 days would the storage capacity of our nervous system be
      reached if we stored every bit of input. The nervous system relies on at least
      two mechanisms that counteract this capacity limit: compression and forgetting.
      But the latter mechanism needs to know how long an entity should be stored: some
      memories are relevant only for the next few minutes, some are important even
      after the passage of several years. Psychology and physiology have found and
      described many different memory mechanisms, and these mechanisms indeed use
      different time scales. In this prospect we review these mechanisms with respect
      to their time scale and propose relations between mechanisms in learning and
      memory and their underlying physiological basis.

PMID- 23160713
TI  - Trends in bipolar disorder or depression as a cause of death on death
      certificates of US residents, 1999-2009.
AB  - BACKGROUND: Temporal trends in mortality from bipolar disorder (BD) or depression
      in the US population, based on multiple causes (MC) rather than underlying cause
      (UC) alone on death certificates, apparently have not been examined. METHOD: The
      annual US age-standardized rate (ASR) for deaths per 100,000 US residents age 15+
      years, and age-specific rates, for BD or depression using MC versus UC alone was
      examined for 1999-2009; percentage change (PC) from 1999 to 2009 was calculated.
      RESULTS: The ASRs at age 15+ years were much higher using MC than UC alone. For
      BD using MC, the ASR increased from 1999 to 2009 (PC +69.2 %) with larger
      increases in age groups within 15-64 years (PCs about 200 %). For depression
      using MC, the ASR rose from 1999 to 2003 and then declined, but the decline was
      restricted to age 65+ years; the ASR at age 15-64 years increased from 1999 to
      2009 (PC +55.5 %). For deaths at age 15-64 years with BD or depression as other
      than UC, the ASRs increased for external causes, cardiovascular diseases,
      external causes, and neoplasms as UC. CONCLUSION: The large increases in
      mortality from BD using MC are consistent with reported increases in BD
      prevalence rates in the US population. The temporal increases in death rates
      related to mood disorders at age 15-64 years may provide further support for the
      need for interventions to address the mediators of excess mortality identified
      from cohort studies.

PMID- 23160714
TI  - Diet quality and mental health problems in adolescents from East London: a
      prospective study.
AB  - PURPOSE: In this study, we aimed to examine the relationship between diet quality
      and depression in a prospective study of adolescents from varied ethnic and
      cultural backgrounds. DESIGN: In this prospective cohort study, data were
      collected at two time points (2001 and 2003) from nearly 3,000 adolescents, aged
      either 11-12 years or 13-14 years, participating in RELACHS, a study of
      ethnically diverse and socially deprived young people from East London in the UK.
      Diet quality was measured from dietary questionnaires, and mental health assessed
      using the Strengths and Difficulties Questionnaire (SDQ) and the Short Mood and
      Feelings Questionnaire (SMFQ). RESULTS: In cross-sectional analyses, we found
      evidence for an association between an unhealthy diet and mental health problems.
      Compared to those in the lowest quintile of Unhealthy diet score, those in the
      highest quintile were more than twice as likely to be symptomatic on the SDQ (OR
      2.10, 95 %CI 1.38-3.20) after taking all identified confounders into account.
      There was also some evidence for a cross-sectional inverse association between a
      measure of healthy diet and mental health problems. A prospective relationship
      between the highest quintiles of both Healthy (OR 0.63, 95 %CI 0.38-1.05) and
      Unhealthy (OR 1.75, 95 %CI 1.00-3.06) diet scores and SDQ scores at follow-up was
      also evident, but was attenuated by final adjustments for confounders.
      CONCLUSION: This study is concordant with previous observational studies in
      describing relationships between measures of diet quality and mental health
      problems in adolescents.

PMID- 23160718
TI  - Atmospheric aerosols at a regional background Himalayan site--Mukteshwar, India.
AB  - Continuous aerosol measurements were made at a regional background station
      (Mukteshwar) located in a rural Himalayan mountain terrain from December 2005 to
      December 2008 for a period of 3 years. The average concentrations of particulate
      matter less than or equal to 10 MUm (PM10), particulate matter less than or equal
      to 2.5 MUm (PM2.5) and black carbon (BC) are 46.0, 26.6 and 0.85 MUg/m(3) during
      the study period. Majority of the PM10 values lie below 100 MUg/m(3) while
      majority of the PM2.5 values lie below 30 MUg/m(3). It is further seen that
      during the monsoon months, especially July and August, the average values are
      comparatively low. It is also noted that the PM2.5/PM10 ratios between 0.50 and
      0.75 have the maximum frequency distribution in the data set. Furthermore, the
      monthly mean ratio of BC to PM2.5 mass lies between 3.0 and 7.5 % during the
      study period. Though the average PM10 and PM2.5 concentrations during the study
      period are less than the respective Indian ambient air quality standards,
      however, they are still above the WHO guidelines and would have adverse health
      impacts. This shows that even in rural/background regions that are far away from
      major pollution sources or urban areas, the aerosol concentrations are
      significant and require long-term monitoring, source quantification and aerosol
      model simulations.

PMID- 23160719
TI  - The effect of atmospheric pressure on CH4 and CO2 emission from a closed landfill
      site in Manchester, UK.
AB  - A time series study was conducted to ascertain the effect of barometric pressure
      on the variability of CH4 and CO2 concentrations in a closed landfill site. An in
      situ data of methane/carbon dioxide concentrations and environmental parameters
      were collected by means of an in-borehole gas monitor, the GasClam (Ion Science,
      UK). Linear regression analysis was used to determine the strength of the
      correlation between ground-gas concentrations and barometric pressure. The result
      shows CH4 and CO2 concentrations to be variable with weak negative correlations
      of 0.2691 and 0.2773, respectively, with barometric pressure over the entire
      monitoring period. Although the R(2) was slightly improved by considering their
      concentration over single periods of rising and falling pressure, single periods
      of rising pressure and single periods of falling pressure, their correlations
      remained insignificant at 95% confidence level. The result revealed that
      atmospheric pressure--the acclaimed major control on the variability of ground
      gas concentration--is not always so. A case was made for the determination of
      other possible controls such as changes in temperature, soil permeability,
      landfill water depth, season, and geology of the borehole and also how much of
      control each factor would have on the variability/migration of CH4 and CO2
      concentrations from the studied landfill.

PMID- 23160720
TI  - Soil heavy metal contamination in an industrial area: analysis of the data
      collected during a decade.
AB  - Soil contamination by heavy metals has become a serious problem mainly because,
      above certain concentrations, all metals have adverse effects on human health. In
      particular, the accumulation of heavy metals in agricultural soils leads to
      elevated uptake by crops and affects food quality and safety. In this paper, we
      present the results of a study carried out over a decade for evaluating the
      impact of a new industrial settlement in an area geared to agriculture and
      livestock and far from urban sites. We focus our study on the bioavailable
      fraction of Cd, Co, Cr, Cu, Fe, Mn, Ni, Pb and Zn in soil samples. Heavy metal
      concentrations in soil are analysed with both univariate and multivariate
      statistical procedures. The main goal of this paper is the development of a
      statistical procedure, based on a mix of multivariate analysis, able to compare
      field surveys carried out during different years and to characterize spatial and
      temporal changes in soil heavy metals concentrations.

PMID- 23160721
TI  - Macro- and microstructural magnetic resonance imaging indices associated with
      diabetes among community-dwelling older adults.
AB  - OBJECTIVE: To better understand the association between diabetes and cognitive
      impairment, we evaluated macro- and microstructural brain MRI measures for the
      total brain and regions of interest (ROIs) in a group of community-dwelling
      elders with and without diabetes. RESEARCH DESIGN AND METHODS: MRI measures were
      obtained on 308 elders (mean age 83.3 years; n = 85 with diabetes) from the
      Health ABC Healthy Brain Substudy. We performed a series of linear regressions
      and used standardized beta values to estimate the cross-sectional association
      between diabetes and macrostructural (gray matter volume [GMV] and white matter
      hyperintensities [WMHs]) and microstructural (mean diffusivity [MD] and
      fractional anisotropy [FA]) measures for the total brain and ROIs. Models were
      adjusted for age, race, and sex; GMV values for ROIs were also adjusted for total
      brain volume (TBV). RESULTS: In multivariate-adjusted models, diabetes was
      associated with lower total GMV (P = 0.0006), GMV in the putamen (P = 0.02 for
      left and right), and TBV (P = 0.04) and greater cerebral atrophy (P = 0.02).
      There was no association with WMHs. On microstructural measures, diabetes was
      associated with reduced FA for total white matter (P = 0.006) and greater MD for
      the hippocampus (P = 0.006 left; P = 0.01 right), dorsolateral prefrontal cortex
      (P = 0.0007, left; P = 0.002, right), left posterior cingulate (P = 0.02), and
      right putamen (P = 0.02). Further adjustment for stroke, hypertension, and
      myocardial infarction produced similar results. CONCLUSIONS: In this cross
      sectional study, elders with diabetes compared with those without had greater
      brain atrophy and early signs of neurodegeneration. Further studies are needed to
      determine whether these structural changes associated with diabetes predict risk
      of cognitive decline.

PMID- 23160722
TI  - Vitamin D Receptor Fok-I polymorphism modulates diabetic host response to vitamin
      D intake: need for a nutrigenetic approach.
AB  - OBJECTIVE: Interpopulation as well as interindividual variations in response to
      vitamin D intake commonly observed in subjects with type 2 diabetes may be
      related to genetic makeup. One of the candidate genes potentially responsible for
      this diversity is vitamin D receptor (VDR). This study aimed to investigate the
      interactive effect of VDR Fok-I polymorphism and vitamin D intake on diverse
      aspects of diabetic host response. RESEARCH DESIGN AND METHODS: Glycemic status,
      lipid profiles, inflammatory biomarkers, and VDR Fok-I genotypes were determined
      in diabetic subjects (n = 140) who participated in a randomized controlled trial.
      Participants consumed two 250-mL bottles per day of yogurt drink (doogh)
      fortified with 500 IU vitamin D/250 mL for 12 weeks. RESULTS: Mean serum 25(OH)D
      increased by ~30 nmol/L (P < 0.001). The time * intervention effect was
      significant for 25(OH)D (P = 0.030), HDL (P = 0.011), high-sensitivity C-reactive
      protein (hsCRP) (P < 0.001), interleukin (IL)-4 (P = 0.008), and IL-6 (P = 0.017)
      among the genotypic groups. The alleles were defined as ''F'' or ''f'' depending
      on the absence or presence of the restriction site, respectively. The least
      increment in 25(OH)D was in ff (23.0 +/- 3.8 nmol/L) compared with Ff (31.2 +/-
      3.4 nmol/L) and FF (35.6 +/- 2.7 nmol/L) (P for trend = 0.009), but only the
      difference between ff and FF was significant (P = 0.023). FF group had the
      largest decrement of both hsCRP and IL-6 compared with Ff (P < 0.001 and P =
      0.038) and ff (P = 0.010 and P = 0.048), respectively. CONCLUSIONS: We concluded
      that those of VDR ff genotype may be regarded as "low responders" to vitamin D
      intake in terms of response of circulating 25(OH)D and certain inflammatory
      biomarkers. A nutrigenetic approach may, therefore, be needed to protect diabetic
      patients from vitamin D deficiency.

PMID- 23160723
TI  - Association of electrocardiographically determined left ventricular mass with
      incident diabetes, 1985-1986 to 2010-2011: Coronary Artery Risk Development in
      Young Adults (CARDIA) study.
AB  - OBJECTIVE: Electrocardiographic indices reflecting left ventricular hypertrophy
      are associated with incident diabetes in clinical populations at risk for
      coronary heart disease. We tested whether electrocardiographically determined
      left ventricular mass was positively associated with incident diabetes in a
      population sample. RESEARCH DESIGN AND METHODS: Coronary Artery Risk Development
      in Young Adults (CARDIA) study participants (n = 4,739) were followed from 1985
      1986 to 2010-2011 for incident diabetes. Validated sex- and race-specific
      formulas were applied to standard electrocardiograms to determine left
      ventricular mass. RESULTS: Over 25 years, 444 participants developed diabetes
      (9.4%). After adjustment for demographic, behavioral, and clinical covariates,
      participants in the highest quartile of left ventricular mass index (LVMI) were
      twice as likely to develop diabetes than participants in the lower three
      quartiles (hazard ratio 2.61 [95% CI 2.16-3.17]). Neither Cornell voltage nor
      Cornell voltage product was associated with incident diabetes in fully adjusted
      models. CONCLUSIONS: Electrocardiographically determined LVMI may be a useful
      noninvasive marker for identifying adults at risk for diabetes.

PMID- 23160724
TI  - The combined effect of leisure-time physical activity and diabetes on
      cardiovascular mortality: the Nord-Trondelag Health (HUNT) cohort study, Norway.
AB  - OBJECTIVE: To examine if leisure-time physical activity could cancel out the
      adverse effect of diabetes on cardiovascular mortality. RESEARCH DESIGN AND
      METHODS: This study prospectively examined the combined effect of clinical
      diabetes and reported leisure-time physical activity on cardiovascular mortality.
      Data on 53,587 Norwegian men and women participating in the population-based Nord
      Trondelag Health (HUNT) Study (1995-1997) were linked with the Cause of Death
      Registry at Statistics Norway. RESULTS: Overall, 1,716 people died of
      cardiovascular disease during follow-up through 2008. Compared with the reference
      group of 3,077 physically inactive people without diabetes, 121 inactive people
      with diabetes had an adjusted hazard ratio (HR) of 2.81 (95% CI 1.93-4.07). The
      HR (95% CI) among people who reported >=3 h of light activity per week was 0.89
      (0.48-1.63) if they had diabetes (n = 403) and 0.78 (0.63-0.96) if they did not
      (n = 17,714). Analyses stratified by total activity level showed a gradually
      weaker association of diabetes with mortality with increasing activity level
      (P(interaction) = 0.003). CONCLUSIONS: The data suggest that even modest physical
      activity may cancel out the adverse impact of diabetes on cardiovascular
      mortality.

PMID- 23160725
TI  - Long-term changes in adiposity and glycemic control are associated with past
      adenovirus infection.
AB  - OBJECTIVE: Ad36, a human adenovirus, increases adiposity but improves glycemic
      control in animal models. Similarly, natural Ad36 infection is cross-sectionally
      associated with greater adiposity and better glycemic control in humans. This
      study compared longitudinal observations in indices of adiposity (BMI and body
      fat percentage) and glycemic control (fasting glucose and insulin) in Ad36
      infected versus uninfected adults. RESEARCH DESIGN AND METHODS: Baseline sera
      from Hispanic men and women (n = 1,400) were screened post hoc for the presence
      of Ad36-specific antibodies. Indices of adiposity and glycemic control at
      baseline and at ~10 years past the baseline were compared between seropositive
      and seronegative subjects, with adjustment for age and sex. In addition to age
      and sex, indices of glycemic control were adjusted for baseline BMI and were
      analyzed only for nondiabetic subjects. RESULTS: Seropositive subjects (14.5%)
      had greater adiposity at baseline, compared with seronegative subjects.
      Longitudinally, seropositive subjects showed greater adiposity indices but lower
      fasting insulin levels. Subgroup analyses revealed that Ad36-seropositivity was
      associated with better baseline glycemic control and lower fasting insulin levels
      over time in the normal-weight group (BMI <=25 kg/m(2)) and longitudinally, with
      greater adiposity in the overweight (BMI 25-30 kg/m(2)) and obese (BMI >30
      kg/m(2)) men. Statistically, the differences between seropositive and
      seronegative individuals were modest in light of the multiple tests performed.
      CONCLUSIONS: This study strengthens the plausibility that in humans, Ad36
      increases adiposity and attenuates deterioration of glycemic control.
      Panoptically, the study raises the possibility that certain infections may
      modulate obesity or diabetes risk. A comprehensive understanding of these under
      recognized factors is needed to effectively combat such metabolic disorders.

PMID- 23160726
TI  - The efficacy and safety of imeglimin as add-on therapy in patients with type 2
      diabetes inadequately controlled with metformin monotherapy.
AB  - OBJECTIVE: A 12-week study assessed the efficacy and safety of a new oral
      antidiabetic agent, imeglimin, as add-on therapy in type 2 diabetes patients
      inadequately controlled with metformin alone. RESEARCH DESIGN AND METHODS: A
      total of 156 patients were randomized 1:1 to receive imeglimin (1,500 mg twice a
      day) or placebo added to a stable dose of metformin (1,500-2,000 mg/day). Change
      in A1C from baseline was the primary efficacy outcome; secondary outcomes
      included fasting plasma glucose (FPG) and proinsulin/insulin ratio. RESULTS:
      After 12 weeks, the placebo-subtracted decrease in A1C with metformin-imeglimin
      was -0.44% (P < 0.001). Metformin-imeglimin also significantly improved FPG and
      the proinsulin/insulin ratio from baseline (-0.91 mg/dL and -7.5, respectively)
      compared with metformin-placebo (0.36 mg/dL and 11.81). Metformin-imeglimin
      therapy was generally well-tolerated with a comparable safety profile to
      metformin-placebo. CONCLUSIONS: Addition of imeglimin to metformin improved
      glycemic control and offers potential as a new treatment for type 2 diabetes.

PMID- 23160727
TI  - Early prediction of gestational diabetes mellitus in Vietnam: clinical impact of
      currently recommended diagnostic criteria.
AB  - OBJECTIVE: We aimed to compare the discriminative power of prognostic models for
      early prediction of women at risk for the development of gestational diabetes
      mellitus (GDM) using four currently recommended diagnostic criteria based on the
      75-g oral glucose tolerance test (OGTT). We also described the potential effect
      of application of the models into clinical practice. RESEARCH DESIGN AND METHODS:
      A prospective cross-sectional study of 2,772 pregnant women was conducted at a
      referral maternity center in Vietnam. GDM was determined by the American Diabetes
      Association (ADA), International Association of the Diabetes and Pregnancy Study
      Groups (IADPSG), Australasian Diabetes in Pregnancy Society (ADIPS), and World
      Health Organization (WHO) criteria. Prognostic models were developed using the
      Bayesian model averaging approach, and discriminative power was assessed by area
      under the curve. Different thresholds of predicted risk of developing GDM were
      applied to describe the clinical impact of the diagnostic criteria. RESULTS: The
      magnitude of GDM varied substantially by the diagnostic criteria: 5.9% (ADA),
      20.4% (IADPSG), 20.8% (ADIPS), and 24.3% (WHO). The ADA prognostic model,
      consisting of age and BMI at booking, had the best discriminative power (area
      under the curve of 0.71) and the most favorable cost-effective ratio if
      implemented in clinical practice. Selective screening of women for GDM using the
      ADA model with a risk threshold of 3% gave 93% sensitivity for identification of
      women with GDM with a 27% reduction in the number of OGTTs required. CONCLUSIONS:
      A simple prognostic model using age and BMI at booking could be used for
      selective screening of GDM in Vietnam and in other low- and middle-income
      settings.

PMID- 23160728
TI  - Solution NMR structure of the helicase associated domain BVU_0683(627-691) from
      Bacteroides vulgatus provides first structural coverage for protein domain family
      PF03457 and indicates domain binding to DNA.
AB  - A high-quality NMR structure of the helicase associated (HA) domain comprising
      residues 627-691 of the 753-residue protein BVU_0683 from Bacteroides vulgatus
      exhibits an all alpha-helical fold. The structure presented here is the first
      representative for the large protein domain family PF03457 (currently 742
      members) of HA domains. Comparison with structurally similar proteins supports
      the hypothesis that HA domains bind to DNA and that binding specificity varies
      greatly within the family of HA domains constituting PF03457.

PMID- 23160729
TI  - Omi, a recessive mutation on chromosome 10, is a novel allele of Ostm1.
AB  - Large-scale N-ethyl-N-nitrosourea (ENU) mutagenesis has provided many rodent
      models for human disease. Here we describe the initial characterization and
      mapping of a recessive mutation that leads to degeneration of the incisors,
      failure of molars to erupt, a grey coat colour, and mild osteopetrosis. We mapped
      the omi mutation to chromosome 10 between D10Mit214 and D10Mit194. The Ostm1 gene
      is a likely candidate gene in this region and the grey-lethal allele, Ostm1 ( gl
      ), and omi mutations fail to complement each other. We show that om/om mice have
      reduced levels of Ostm1 protein. To date we have not been able to identify the
      causative mutation. We propose that omi is a novel hypomorphic mutation affecting
      Ostm1 expression, potentially in a regulatory element.

PMID- 23160730
TI  - Comparison of the longissimus muscle proteome between obese and lean pigs at 180
      days.
AB  - Production of high-quality meat is important to satisfy the consumer and make the
      pig industry competitive. Obese and lean breeds of pig show clear differences in
      adipogenic capacity and meat quality, but the underlying molecular mechanism
      remains unclear. We have compared protein expression of the longissimus muscle
      between Lantang (LT, obese) and Landrace (LR, lean) pigs at the age of 180 days
      using two-dimensional fluorescence difference gel electrophoresis. Of the 1,400
      protein spots detected per gel, 18 were differentially expressed between the two
      breeds. Using peptide mass fingerprint and tandem mass spectrometry, 17 protein
      spots were identified, corresponding to ten different proteins that could be
      divided into four groups: metabolism-related, structure-related, stress-related,
      and other (unclassified). Among the metabolism-related proteins, COX5A and ATP5B,
      which participate in oxidative phosphorylation, were highly expressed in LT,
      whereas ENO3, which is involved in glycolysis, was highly expressed in LR. These
      results may contribute valuable information to our understanding of the molecular
      mechanism responsible for differences between obese and lean pigs, such as growth
      rate and meat quality.

PMID- 23160731
TI  - Digestibility of extruded proteins and metabolic transit of N epsilon 
      carboxymethyllysine in rats.
AB  - Milk proteins are frequently used as supplements in fortified foods. However,
      processing produces chemical changes which likely affect the nutritional
      advantage. This study was intended to explore the possible difference in
      digestibility between extruded and non-extruded caseins and how the dietary N
      (epsilon) -carboxymethyllysine (CML) is metabolised. Normal rats were randomized
      into either an extruded protein diet (EP) or the same with unextruded proteins
      (UEP), for two periods of 2 weeks at 7 to 9 and 11 to 13 weeks of age. However,
      no difference in protein digestibility was detected between the two diets, either
      in young or in adult animals, despite a 9.4-fold higher level of CML and an 8.5
      fold higher level of lysinoalanine in the EP than in the UEP. No diet-related
      changes were observed in plasma CML, either protein bound or free. Amounts of 38
      and 48 % of the orally absorbed CML were excreted in urine and faeces,
      respectively, in UEP-fed rats. Lower rates of excretion were found in the EP-fed
      rats (23 and 37 %, respectively). A second animal study using a single oral dose
      of free CML (400 MUg/rat) was set up to measure the systemic concentration of CML
      every hour from 0 to 4 h. It revealed that protein-bound CML was not affected by
      the oral dose of CML, and the highest free CML level found in the circulation was
      600 ng/mL. Extruded proteins, therefore, appear to be well digested, and CML
      rapidly eliminated. Since its elimination is, however, incomplete, the question
      of its biodistribution and metabolism remains open.

PMID- 23160732
TI  - Male peer influence on African American men's motivation for physical activity:
      men's and women's perspectives.
AB  - Thematic analysis of data from nine exploratory focus groups conducted with 71
      middle-aged and older African American men and eight focus groups with 77 key
      women in their lives revealed how social norms and modeling of physical activity
      influenced men's motivation to exercise. Both men and women identified male peers
      as an important source of ideas, encouragement, and support to initiate and
      sustain physical activity, yet sedentary peers also could contribute to men being
      less motivated to be active. The primary difference in men's and women's
      perspectives was that men attributed their decline in activity levels to
      difficulties in finding time for physical activity, whereas women attributed
      sedentary lifestyles to an increase in men's physical illnesses and ailments.
      Men's participation in team sports and overall activity levels diminished with
      age. Peer social support can be critical for interventions to help African
      American men engage in and sustain physical activity.

PMID- 23160733
TI  - Subclinical cardiovascular target organ damage manifestations of ankylosing
      spondylitis in young adult patients.
AB  - AIM: Although it is known that ankylosing spondylitis (AS) is associated with
      cardiovascular complications, the extent of these complications has not been
      clearly demonstrated in young adult patients. We have therefore investigated
      myocardial diastolic functions, carotid intima-media thickness (CIMT), and aortic
      elastic properties of young adult patients diagnosed with AS. METHOD: Sixty-six
      AS patients and 21 age/gender-matched healthy subjects were enrolled in the
      study. Spectral and tissue Doppler echocardiography, CIMT, aortic strain and
      distensibility, and serum B-type natriuretic peptide values were compared with
      disease activity indexes of AS, including the Bath Ankylosing Spondylitis Disease
      Activity Index (BASDAI), and the role of other variables, such as anti-tumor
      necrosis factor-alpha (anti-TNF-alpha) treatment, lipid parameters, erythrocyte
      sedimentation rate, and C-reactive protein. RESULTS: Both mitral early diastolic
      flow speed (mE) and late diastolic flow speed (mA) scores were lower among
      patients than among the control subjects (p = 0.015 and p = 0.035, respectively).
      The Em ratio of the patients was remarkably lower than that of the control
      subjects (p = 0.044). BASDAI scores of >4 were used to identify patients with
      more active disease. The mA and mE/mA ratios were significantly different between
      patients with a BASDAI score of >4 and those with a BASDAI score of <4 (p = 0.026
      and p = 0.021, respectively). While aortic elasticity were not significantly
      different between the groups, AS patients treated with anti-TNF-alpha had
      significantly improved aortic strain and distensibility values (p = 0.022 and p =
      0.014, respectively) compared to those treated with non-steroidal anti
      inflammatory drugs (NSAIDs). CONCLUSION: Myocardial diastolic functions were
      significantly deteriorated in the AS patients, and disease activity and
      myocardial diastolic functions were associated. An interesting finding was that
      patients receiving anti-TNF-alpha had better aortic elasticity than those treated
      with NSAIDs.

PMID- 23160735
TI  - Neuronal overexpression of insulin receptor substrate 2 leads to increased fat
      mass, insulin resistance, and glucose intolerance during aging.
AB  - The insulin receptor substrates (IRS) are adapter proteins mediating insulin's
      and IGF1's intracellular effects. Recent data suggest that IRS2 in the central
      nervous system (CNS) is involved in regulating fuel metabolism as well as memory
      formation. The present study aims to specifically define the role of chronically
      increased IRS2-mediated signal transduction in the CNS. We generated transgenic
      mice overexpressing IRS2 specifically in neurons (nIRS2 (tg)) and analyzed these
      in respect to energy metabolism, learning, and memory. Western blot (WB) analysis
      of nIRS2 (tg) brain lysates revealed increased IRS2 downstream signaling.
      Histopathological investigation of nIRS2 (tg) mice proved unaltered brain
      development and structure. Interestingly, nIRS2 (tg) mice showed decreased
      voluntary locomotoric activity during dark phase accompanied with decreased
      energy expenditure (EE) leading to increased fat mass. Accordingly, nIRS2 (tg)
      mice develop insulin resistance and glucose intolerance during aging. Exploratory
      behavior, motor function as well as food and water intake were unchanged in nIRS2
      (tg) mice. Surprisingly, increased IRS2-mediated signals did not change spatial
      working memory in the T-maze task. Since FoxO1 is a key mediator of IRS2
      transmitted signals, we additionally generated mice expressing a dominant
      negative mutant of FoxO1 (FoxO1DN) specifically in neurons. This mutant mimics
      the effect of increased IRS2 signaling on FoxO-mediated transcription.
      Interestingly, the phenotype observed in nIRS2 (tg) mice was not present in
      FoxO1DN mice. Therefore, increased neuronal IRS2 signaling causes decreased
      locomotoric activity in the presence of unaltered exploratory behavior and motor
      coordination that might lead to increased fat mass, insulin resistance, and
      glucose intolerance during aging independent of FoxO1-mediated transcription. 

PMID- 23160737
TI  - Endogenous signal peptides efficiently mediate the secretion of recombinant
      proteins in Pichia pastoris.
AB  - By predicting the potential signal peptides from proteins that are naturally
      secreted by Pichia pastoris, we identified three possible endogenous signal
      peptides: Scw, Dse and Exg. We compared their capability to mediate the secretion
      of enhanced green fluorescent protein (EGFP) and Candida antarctica lipase B
      (CALB) with that of the Saccharomyces cerevisiae alpha-factor prepro-signal. EGFP
      entered the secretory pathway of P. pastoris and was efficiently secreted into
      the culture medium by all three endogenous peptides. Further, these three
      putative endogenous signal peptides were also effective in secreting CALB. These
      endogenous signal peptides thus have the potential to mediate the efficient
      secretion of heterologous proteins in P. pastoris.

PMID- 23160736
TI  - Socioeconomic status is positively correlated with frontal white matter integrity
      in aging.
AB  - Socioeconomic status (SES) is an important reserve variable which has been shown
      to benefit the aging brain's macrostructure. However, it remains unknown whether
      SES affects age-related changes in the brain's white matter (WM) microstructure.
      Here, we used diffusion tensor imaging to explore the relationship between SES
      and three components of the diffusion tensor [fractional anisotropy (FA), axial
      diffusivity, and radial diffusivity (DR)]. Participants were 40 (16 male)
      cognitively normal young adults (mean age = 33.3 years, SD = 4.27) and 44 (19
      male) cognitively normal community dwelling seniors (mean age = 66.2 years, SD =
      7.5). Age-related FA declines were observed across a large portion of the WM
      skeleton. However, seniors with high SES showed lower age-related WM integrity
      declines in three frontal tracts: the right anterior corona radiata and bilateral
      portions of WM underlying the superior frontal gyri (SFG-WM). Positive SES-FA
      correlations were primarily driven by negative DR-SES correlations, suggesting
      that SES may buffer age-related declines in myelin. The functional significance
      of high SES in these frontal tracts was demonstrated through positive
      correlations with working memory performance. Possible mechanisms through which
      SES may attenuate the effects of age on frontal WM integrity are discussed.

PMID- 23160738
TI  - Metabolic engineering of morphinan alkaloids by over-expression of codeinone
      reductase in transgenic hairy roots of Papaver bracteatum, the Iranian poppy.
AB  - Papaver bracteatum has a high content of thebaine. It is used as an alternative
      to P. somniferum for the production of benzylisoquinoline alkaloid. Papaver
      bracteatum was genetically engineered to over-express codeinone reductase gene in
      hairy root cultures. Transcript level of the codeinone reductase gene in
      transgenic hairy root lines increased up to ten- and 24-fold in comparison with
      hairy roots without CodR over-expression and wild type roots, respectively.
      Codeine was produced at (0.04 % dry wt) and morphine was at (0.28 % dry wt) in
      the transgenic hairy root lines. Papaver bracteatum hairy roots expressing CodR
      gene thus have a high potential to produce morphinan alkaloids.

PMID- 23160739
TI  - Novel technique for internal structure and elemental distribution analyses of
      granular sludge from reactors for wastewater treatment.
AB  - A novel technique for internal structure and elemental distribution analyses of
      granular sludge is presented. Sludge samples were freeze-dried and embedded in
      epoxy resin to form a module, which were then ground and polished to obtain
      sequential cross-sections. The cross-sections were analyzed by scanning electron
      microscopy (SEM) and energy dispersive X-ray spectroscopy (EDX). SEM observations
      showed that one granule was formed having several cores with different inorganic
      minerals, rather than a single core. EDX results indicate that the main elements
      of the granules are O, Ca, Mg, and P. In addition, the distribution areas of
      calcium and magnesium in the granule do not coincide.

PMID- 23160740
TI  - Biocatalytic characterization of a short-chain alcohol dehydrogenase with broad
      substrate specificity from thermophilic Carboxydothermus hydrogenoformans.
AB  - The gene encoding a novel short-chain alcohol dehydrogenase in the thermophilic
      bacterium, Carboxydothermus hydrogenoformans, was identified and overexpressed in
      Escherichia coli. The enzyme was thermally stable and displayed the highest
      activity at 70  degrees C and pH 6.0. It preferred NAD(H) over NADP(H) as a
      cofactor and exhibited broad substrate specificity towards aliphatic ketones,
      cycloalkanones, aromatic ketones, and ketoesters. Furthermore, ethyl
      benzoylformate was asymmetrically reduced by the purified enzyme, using an
      additional coupled NADH regeneration system, with 95 % conversion and in an
      enantiomeric excess of (99.9 %). The results of this study may lead to the
      discovery of a novel method for asymmetric reduction of alcohols, which is an
      important tool in organic synthesis.

PMID- 23160741
TI  - Comparative study of in vitro expansion of bone marrow-derived mesenchymal stem
      cells.
AB  - Bone marrow-derived mesenchymal stem cells (BMD-MSCs) are of great interest for
      tissue engineering, but require expansion before they can be used for therapeutic
      applications. We compared three different culture techniques for their potential
      for large scale expansion of rat BMD-MSCs, i.e. monolayer cultures, stirred
      suspension cultures and pour-off cultures, and found that pour-off cultures
      supported the biggest expansion in BMD-MSCs as measured by the fibroblastic
      colony forming unit assay (CFU-f). BMD-MSCs expanded in stirred suspension
      cultures stopped proliferating altogether and, although monolayer cultures
      allowed for expansion of BMD-MSCs, they favoured a differentiated phenotype over
      uncommitted MSCs. Only BMD-MSCs expanded in pour-off cultures were able to
      differentiate into both osteoblastic and adipocytic lineages and maintain CFU-f
      numbers. These data suggest that pour-off cultures are a viable method of BMD-MSC
      expansion.

PMID- 23160742
TI  - Accelerated myotube formation using bioprinting technology for biosensor
      applications.
AB  - Muscle-powered, biological, microelectro-mechanical system is promising for
      actuator and biosensor applications. Functional conjugation between the cells,
      tissues, and biomolecules to the microdevice is crucial for this application.
      Bioprinting as an enabling technology possesses the advantages of high
      throughput, digital control, and highly accurate delivery of various biological
      factors to the desired locations for numerous applications such as 3D tissue
      fabrication. We have now evaluated the feasibility of the precise placement of
      mouse myoblasts onto micro-sized cantilevers. The evenly aligned printed cells
      fused with each other and formed mature myotubes after only 4 days. In contrast,
      it took more than 14 days for randomly deposited cells to do so. The printed
      myotubes were functional and responded to the electrical stimulation
      synchronously. Furthermore, the integrated Bio-MEMS device responded to the
      chemical stimulation spontaneously which demonstrated the potential as a
      functional biosensor. The contractility of the system was recovered quickly after
      the removal of the chemical stimulation, which indicated the flexibility of this
      system and the recycling potential.

PMID- 23160743
TI  - Efficient biological process characterization by definitive-screening designs:
      the formaldehyde treatment of a therapeutic protein as a case study.
AB  - As part of the process-characterization campaign of a candidate vaccine product,
      a recently developed class of three-level designs-definitive-screening designs
      was employed to select a quadratic model that describes the effect of six input
      process parameters, including protein concentration, formaldehyde-to-protein
      ratio, lysine concentration, reaction duration, pH, and reaction temperature, on
      a formylation protein-crosslinking reaction. This design requires only 17
      experimental runs. The resulting model was then used to simulate 10,000 runs that
      account for the variability in the inputs expected on manufacturing scale. The
      extent of protein polymerization was predicted to be within specifications for
      all simulated runs, demonstrating the robustness of the unit operation for
      subsequent process validation and future commercial manufacturing.

PMID- 23160744
TI  - Dimensionality reduction for microarray data using local mean based discriminant
      analysis.
AB  - A new method is proposed for finding a low dimensional subspace of high
      dimensional microarray data. We developed a new criterion for constructing the
      weight matrix by using local neighborhood information to discover the intrinsic
      discriminant structure in the data. Also this approach applies regularized least
      square technique to extract relevant features. We assess the performance of the
      proposed methodology by applying it to four publicly available tumor datasets. In
      a low dimensional subspace, the proposed method classified these tumors
      accurately and reliably. Also, through a comparison study, we verify the
      reliability of the dimensionality reduction and discrimination results.

PMID- 23160745
TI  - Metal concentrations in marine fishes collected from Hara biosphere in Iran.
AB  - The metal levels (Hg, As, Cu, and Zn) in tissues of edible fish species (Pampus
      argenteus, Sillago sihama, Liza klunzingeri and Platycephalus indicus) were
      evaluated. The metal concentrations were found to follow the order: liver >
      kidney > gill > muscle, except for Zn from P. argenteus showing an inversion of
      liver and kidney. Generally, the benthic species (P. indicus and S. sihama)
      showed a marked potential for tolerating high metal levels. Significant negative
      correlations were found between fish size/age and metals concentration in the
      most organs. The element levels in the muscles were lower than the maximum
      allowable concentrations, except for mercury in S. sihama and P. indicus.

PMID- 23160746
TI  - Accumulation and phytoavailability of hexachlorocyclohexane isomers and cadmium
      in Allium sativum L. under the stress of hexachlorocyclohexane and cadmium.
AB  - The effects of Cd and HCHs with single and combined forms on Cd and HCHs
      phytoavailability of Allium sativum L. were investigated. The results indicated
      that the coexistence of Cd and HCHs presented antagonistic interactions mostly,
      which might be partly due to the formation of Cd-HCHs complex, compared with
      single stress. The bioaccumulation of Cd and HCHs in plants depended largely on
      their concentrations applied in pot soils, and the phytoavailability of HCH
      isomers was in the sequence: delta- > gamma- >= beta- > alpha-HCH.

PMID- 23160747
TI  - Real-time PCR investigation of the dynamic expression of three "RNA processing
      and modification" genes of Phanerochaete chrysosporium exposed to lead.
AB  - The expression of three ribosome binding proteins namely; polyadenylate-binding
      protein, splicing factor RNPS1 and ATP-dependent RNA helicase of Phanerochaete
      chrysosporium exposed to lead were analyzed by real-time PCR. The mRNA level of
      splicing factor RNPS1 showed 2.7 (p < 0.05), 2.6 (p < 0.05) and 4.9-fold (p <
      0.001) increase when the cells were exposed to 25, 50 and 100 MUM lead,
      respectively. 50 and 100 MUM lead exposure resulted in almost 2-fold (p < 0.01and
      p < 0.05, respectively) increase in the expression of ATP-dependent RNA helicase.
      Polyadenylate-binding protein mRNA levels did not reveal any significant increase
      when cells exposed to the concentrations of lead employed. However, the mRNA
      level of polyadenylate-binding protein and splicing factor RNPS1 within a period
      of 1 and 2 h temporal exposure to 100 MUM lead showed 2.5 (p < 0.001) and 3.4
      fold (p < 0.001) increase, respectively. Expression level of ATP-dependent RNA
      helicase was not affected from the period of exposure to this metal.

PMID- 23160748
TI  - Occurrence of bisphenol A, estrone, 17beta-estradiol and 17alpha-ethinylestradiol
      in Portuguese rivers.
AB  - This study focused on the occurrence of several EDCs including bisphenol A,
      estrone (E1), the 17beta-estradiol (E2) and 17alpha-ethinylestradiol (EE2) in
      fourteen rivers of Portugal. Samples analysis revealed a widespread contamination
      of BPA especially in Ave, Cavado, Douro, Ferro, Sousa and Vizela Rivers.
      Achieving 98.4 ng/L for the highest concentration. The estrogens achieved above
      the method quantification limit (MQL) were E1 in Agueda River and E2 in Ave, Lima
      and Tamega Rivers. The maximum concentration detected for E1 was 26.9 ng/L. EE2
      was detected only below MQL.

PMID- 23160749
TI  - Polychlorinated dibenzo-p-dioxins and dibenzofurans in the sediment core from a
      schistosomiasis area with Na-PCP application in China.
AB  - Spatial and temporal distribution of polychlorinated dibenzo-p-dioxins and
      dibenzofurans (PCDD/Fs) was explored in the Dongting Lake area. The
      concentrations of total PCDD/Fs ranged from 15.4 to 38.9 pg I-TEQ g(-1) in
      surface sediments and 0.55 to 38.9 pg I-TEQ g(-1) for sediment core. The vertical
      distributions of PCDD/Fs in the sediment core reflected the past history of using
      Na-PCP and the impact of the massive flood events on the distribution of PCDD/Fs
      to some extent. The sediment still acts as significant PCDD/F sources and they
      would pose a risk to sensitive species, resulting in the risk for human exposure
      to PCDD/F.

PMID- 23160751
TI  - Predicting the risk of an asthma attack: the way ahead?

PMID- 23160750
TI  - Survey of hazardous organic compounds in the groundwater, air and wastewater
      effluents near the Tehran automobile industry.
AB  - Potential of wastewater treatment in car industry and groundwater contamination
      by volatile organic compounds include perchloroethylene (PCE), trichloroethylene
      (TCE) and dichloromethane (DCM) near car industry was conducted in this study.
      Samples were collected in September through December 2011 from automobile
      industry. Head-space Gas chromatography with FID detector is used for analysis.
      Mean PCE levels in groundwater ranged from 0 to 63.56 MUg L(-1) with maximum
      level of 89.1 MUg L(-1). Mean TCE from 0 to 76.63 MUg L(-1) with maximum level of
      112 MUg L(-1). Due to the data obtained from pre treatment of car staining site
      and conventional wastewater treatment in car factory, the most of TCE, PCE and
      DCM removed by pre aeration. Therefor this materials entry from liquid phase to
      air phase and by precipitation leak out to the groundwater. As a consequence
      these pollutants have a many negative health effect on the workers by air and
      groundwater.

PMID- 23160752
TI  - Expanding the coordination chemistry of donor-stabilized group-14 metalenes.
AB  - The transformation of an amidinate germylene, equipped with just one accessible
      lone pair of electrons on the Ge atom, into a bidentate 4-electron donor
      kappa(2)Ge,N-ligand, has been achieved for the first time, opening new doors to
      the non-carbene-like coordination chemistry of heavier carbene analogues.

PMID- 23160753
TI  - Inflammatory bowel disease: an impaired barrier disease.
AB  - BACKGROUND: The intestinal barrier is a delicate structure composed of a single
      layer of epithelial cells, the mucus, commensal bacteria, immune cells, and
      antibodies. Furthermore, a wealth of antimicrobial peptides (AMPs) can be found
      in the mucus and defend the mucosa. Different lines of investigations now point
      to a prominent pathophysiological role of defensins, an important family of AMPs,
      in the pathogenesis of inflammatory bowel disease and, particularly, in small
      intestinal Crohn's disease. PURPOSE: In this review, we introduce the different
      antimicrobial peptides of the intestinal mucosa and describe their function,
      their expression pattern along the gastrointestinal tract, and their spatial
      relationship to the mucus layer. We then focus on the alterations found in
      inflammatory bowel disease. Small intestinal Crohn's disease (CD) is closely
      linked to defects in Paneth cells (specialized secretory epithelial cells at the
      bottom crypts) which secrete alpha-defensin human defensin (HD)-5 in huge
      quantities in healthy individuals. Decreased expression of these antimicrobial
      peptides is found in ileal CD, and single nucleotide polymorphisms with the
      highest linkage to CD affect genes involved in Paneth cell biology and defensin
      secretion. Additionally, antimicrobial peptides have a role in ulcerative
      colitis, where the depleted mucus layer cannot fulfill its crucial function of
      binding defensins and other AMPs to their proper site of action. CONCLUSION:
      Inflammatory bowel disease arises when the mucosal barrier is compromised in its
      defense against challenges from the intestinal microbiota. In ileal CD, a strong
      association can be found between diminished expression or defective function of
      defensins and the advent of intestinal inflammation.

PMID- 23160755
TI  - Oral bioavailability of linezolid before and after Roux-en-Y gastric bypass
      surgery: is dose modification necessary in obese subjects?
AB  - OBJECTIVES: We characterized the pharmacokinetics of intravenous (iv) and oral
      linezolid before and after Roux-en-Y gastric bypass surgery (RYGBS). METHODS:
      Subjects with a body mass index (BMI)  >35 kg/m(2) received a single iv 600 mg
      dose of linezolid followed by the same oral dose after a 7 day washout period
      between doses, before and 3 months after RYGBS. Serum linezolid concentrations
      were measured by a validated HPLC method with ultraviolet detection. Parametric
      population pharmacokinetic analysis was used to evaluate bioavailability and the
      influence of total body weight (TBW) on pharmacokinetic parameters. The area
      under the serum concentration-time curve extrapolated to infinity (AUC(0
      infinity)) was compared between subjects before and after RYGBS, and with non
      obese controls. RESULTS: Five (four male) obese subjects were studied with a mean
      (SD) age of 51.4 (5.01) years, TBW of 124 (10.6) kg and initial BMI of 44.9
      (7.52) kg/m(2). The bioavailability was a mean (95% CI) of 1.14 (0.816-1.47)
      before and 1.14 (1.01-1.26) after RYGBS. The mean (SD) AUC(0-infinity) with oral
      linezolid before RYGBS was 41.6 (20.9) mg h/L compared with 98.9 (24.7) mg h/L
      after RYGBS (P<0.001). This increase in AUC(0-infinity) corresponded with a 25.3%
      reduction in the TBW after RYGBS, as the TBW was a significant covariate of
      clearance. The probability of pharmacodynamic target attainment with standard
      doses of linezolid is lower in obese versus non-obese individuals. CONCLUSIONS:
      The bioavailability of linezolid is not impaired by RYGBS. The serum exposure of
      linezolid is more than 50% lower in obese compared with non-obese subjects,
      suggesting that dose modification may be needed.

PMID- 23160754
TI  - Estimating the rotation rate in the vacuolar proton-ATPase in native yeast
      vacuolar membranes.
AB  - The rate of rotation of the rotor in the yeast vacuolar proton-ATPase (V-ATPase),
      relative to the stator or steady parts of the enzyme, is estimated in native
      vacuolar membrane vesicles from Saccharomyces cerevisiae under standardised
      conditions. Membrane vesicles are formed spontaneously after exposing purified
      yeast vacuoles to osmotic shock. The fraction of total ATPase activity
      originating from the V-ATPase is determined by using the potent and specific
      inhibitor of the enzyme, concanamycin A. Inorganic phosphate liberated from ATP
      in the vacuolar membrane vesicle system, during ten min of ATPase activity at 20 
      degrees C, is assayed spectrophotometrically for different concanamycin A
      concentrations. A fit of the quadratic binding equation, assuming a single
      concanamycin A binding site on a monomeric V-ATPase (our data are incompatible
      with models assuming multiple binding sites), to the inhibitor titration curve
      determines the concentration of the enzyme. Combining this with the known
      ATP/rotation stoichiometry of the V-ATPase and the assayed concentration of
      inorganic phosphate liberated by the V-ATPase, leads to an average rate of ~10 Hz
      for full 360 degrees  rotation (and a range of 6-32 Hz, considering the +/-
      standard deviation of the enzyme concentration), which, from the time-dependence
      of the activity, extrapolates to ~14 Hz (8-48 Hz) at the beginning of the
      reaction. These are lower-limit estimates. To our knowledge, this is the first
      report of the rotation rate in a V-ATPase that is not subjected to genetic or
      chemical modification and is not fixed to a solid support; instead it is
      functioning in its native membrane environment.

PMID- 23160756
TI  - How do I treat inflammatory breast cancer?
AB  - Inflammatory breast cancer (IBC) is an uncommon and aggressive presentation of
      locally advanced breast cancer that is potentially curable when localized but may
      be associated with distant metastasis in up to one-third of patients at
      presentation. The diagnosis of IBC is made based on clinical features, including
      the presence of skin edema and erythema involving at least one-third of the
      breast, with or without a mass, and usually associated with dermal lymphatic
      invasion (DLI) on skin biopsy. Management requires combined modality therapy,
      including neoadjuvant chemotherapy with an anthracycline and taxane-based
      regimen, followed by surgery and radiotherapy, plus concurrent anti-HER2 therapy
      for HER2-positive disease, and endocrine therapy for at least 5 years after
      surgery for estrogen-receptor-positive disease (Fig. 1). There have been few
      large clinical trials focused on IBC; therefore, most data regarding treatment
      are derived from retrospective analyses, small studies, and extrapolation of
      results from trials of noninflammatory locally advanced breast cancer. Patients
      with IBC should be encouraged to enroll in clinical trials whenever possible. In
      addition, further research into the biology of IBC may help to elucidate the
      mechanisms underlying its aggressive clinical behavior and to assist in the
      development of therapies targeted for this specific population.

PMID- 23160757
TI  - Elucidating the mechanism of ferrocytochrome c heme disruption by peroxidized
      cardiolipin.
AB  - The interaction of peroxidized cardiolipin with ferrocytochrome c induces two
      kinetically and chemically distinct processes. The first is a rapid oxidation of
      ferrocytochrome c, followed by a slower, irreversible disruption of heme c. The
      oxidation of ferrocytochrome c by peroxidized cardiolipin is explained by a
      Fenton-type reaction. Heme scission is a consequence of the radical-mediated
      reactions initiated by the interaction of ferric heme iron with peroxidized
      cardiolipin. Simultaneously with the heme c disruption, generation of hydroxyl
      radical is detected by EPR spectroscopy using the spin trapping technique. The
      resulting apocytochrome c sediments as a heterogeneous mixture of high
      aggregates, as judged by sedimentation analysis. Both the oxidative process and
      the destructive process were suppressed by nonionic detergents and/or high ionic
      strength. The mechanism for generating radicals and heme rupture is presented.

PMID- 23160758
TI  - An exploratory, placebo-controlled, dose-response study of the efficacy and
      safety of onabotulinumtoxinA in spinal cord injury patients with urinary
      incontinence due to neurogenic detrusor overactivity.
AB  - PURPOSE: To explore the dose response to onabotulinumtoxinA 50, 100, and 200 U in
      patients with spinal cord injury (SCI) with urinary incontinence (UI) due to
      neurogenic detrusor overactivity (NDO). METHODS: Patients (N = 73) with SCI
      (level T1 or lower) with NDO and UI (>=14 UI episodes/week) received 30
      intradetrusor injections of onabotulinumtoxinA (50 U [n = 19], 100 U [n = 21], or
      200 U [n = 17]) or placebo (n = 16) via cystoscopy, avoiding the trigone. Changes
      from baseline in UI episodes/week, volume voided/micturition, maximum cystometric
      capacity, and maximum detrusor pressure (MDP) during first involuntary detrusor
      contraction (IDC) were evaluated. Adverse events (AEs) were assessed. RESULTS: A
      significant linear dose response for UI episodes/week was identified at weeks 18,
      30, 36, 42, and 54 (P < 0.05) with a similar trend (P = 0.092) at week 6 (primary
      time point). A significant linear dose response was observed in volume/void at
      all post-treatment time points up to week 54 (P < 0.05) and in MDP during first
      IDC at week 6 (P = 0.034). The proportion of patients who achieved continence at
      week 6 was highest in the 200 U group. Duration of effect was longest with the
      200 U dose, compared with other treatment groups. The AEs were comparable across
      groups; urinary tract infection was the most common AE across all treatment
      groups. CONCLUSIONS: In this exploratory dose-response study of SCI patients with
      UI due to NDO, onabotulinumtoxinA 200 U was the most effective dose. The AE
      profile was comparable across all groups.

PMID- 23160759
TI  - Pudendal nerve block in HDR-brachytherapy patients: do we really need general or
      regional anesthesia?
AB  - PURPOSE: In male patients, the pudendal block was applied only in rare cases as a
      therapy of neuralgia of the pudendal nerve. We compared pudendal nerve block
      (NPB) and combined spinal-epidural anesthesia (CSE) in order to perform a pain
      free high-dose-rate (HDR) brachytherapy in a former pilot study in 2010.
      Regarding this background, in the present study, we only performed the bilateral
      perineal infiltration of the pudendal nerve. METHODS: In 25 patients (71.8 +/-
      4.18 years) suffering from a high-risk prostate carcinoma, we performed the HDR
      brachytherapy with the NPB. The perioperative compatibility, the subjective
      feeling (German school marks principle 1-6), subjective pain (VAS 1-10) and the
      early postoperative course (mobility, complications) were examined. RESULTS: All
      patients preferred the NPB. There was no change of anesthesia form necessary. The
      expense time of NPB was 10.68 +/- 2.34 min. The hollow needles (mean 24, range 13
      27) for the HDR-brachytherapy remained on average 79.92 +/- 12.41 min. During and
      postoperative, pain feeling was between 1.4 +/- 1.08 and 1.08 +/- 1.00. A
      transurethral 22 French Foley catheter was left in place for 6 h. All patients
      felt the bladder catheter as annoying, but they considered postoperative mobility
      as more important as complete lack of pain. The subjective feeling was described
      as 2.28 +/- 0.74. Any side effects or complications did not appear. CONCLUSIONS:
      Bilateral NPB is a safe and effective analgesic option in HDR-brachytherapy and
      can replace CSE. It offers the advantage of almost no impaired mobility of the
      patient and can be performed by the urologist himself. Using transrectal
      ultrasound guidance, the method can be learned quickly.

PMID- 23160760
TI  - Call for research: detecting early vulnerability for psychiatric hospitalization.
AB  - This study delineated the extent to which a broad set of risk factors in youth, a
      period well suited to primary prevention strategies, influences the likelihood
      and timing of first lifetime psychiatric hospitalizations. Logistic regression
      was used to delineate early risk factors for psychiatric hospitalization among
      Americans in a nationally representative survey (NCS-R, Part II, 2001-2003: N =
      5,692). Results suggest that inpatient stay is more common and happens at earlier
      ages among Americans who report growing up with versus without: (1) depressed
      parents or caregivers, (2) family members who victimized them, or (3) one of
      three child mental illnesses (conduct, oppositional defiant, or separation
      anxiety disorder). In order to prevent inpatient stay, findings call for
      longitudinal research on early vulnerability for psychiatric hospitalization
      among families with: (1) depressed parents of children or adolescents, (2)
      violence against children, and (3) children that have externalizing or separation
      anxiety disorders.

PMID- 23160761
TI  - The effect of parental involvement on problematic social behaviors among school
      age children in Kentucky.
AB  - This study examines the associations among parental active involvement and
      healthy role modeling behavior with social behavior among children in Kentucky
      and the nation. Data from the 2007 National Survey of Children's Health was used,
      limited to children 6-17 years old. The dependent variable was a composite
      measure of problematic social behavior. Independent variables included parental
      involvement, parental healthy role modeling, and demographic variables. Chi
      square tests of independence were completed for bivariate analyses and
      multivariable logistic regression models were developed for Kentucky and the
      nation. The prevalence of problematic social behaviors in children was 10.4 % in
      Kentucky and 8.8 % in the nation. The parents of children in Kentucky who often
      exhibited problematic social behavior reported poor parent-child communication
      (50.4 %), not coping well with parenthood (56.5 %), parental aggravation (48.3
      %), and less emotional help with parenting (9.1 %). The factor with the largest
      magnitude of association in Kentucky (adjusted odds ratio [AOR] = 6.2; 95 %
      confidence interval [CI]: 1.6, 24.5) and the nation (AOR = 4.8; 95 % CI: 3.3,
      7.0) was observed for whether or not the parent communicated well with the child.
      Additional factors associated with problematic social behavior among children in
      Kentucky were living in a single parent, mother-led household, and having a
      parent with fair or poor mental health. Public health programs that target
      factors addressing the parent-child dyad, parent-child communication, and model
      healthy relationships may reduce the occurrence of problematic social behavior in
      6-17-year-old children in Kentucky.

PMID- 23160762
TI  - Associations between neighborhood characteristics and physical activity among
      youth within rural-urban commuting areas in the US.
AB  - The association among rural-urban communities, neighborhood characteristics, and
      youth physical activity is inconsistent in the literature. We used data from the
      2007 National Survey of Children's Health, for youth aged 10-17 years (n =
      45,392), to examine the association between physical activity and neighborhood
      characteristics, after adjusting for known confounders. We also examined the
      association between physical activity and neighborhood characteristics within
      seven levels of Rural-Urban Commuting Areas (RUCAs) that depict a continuum from
      isolated rural to dense urban communities. Attainment of a minimum physical
      activity level differed by RUCA (P = 0.0004). In adjusted, RUCA-specific models,
      the presence of parks was associated with attaining a minimum physical activity
      level in only one of the seven RUCAs (adjusted odds ratio: 3.49; 95 % confidence
      interval: 1.55, 7.84). This analysis identified no association between youths'
      minimum physical activity attainment and neighborhood characteristics in
      unstratified models; and, RUCA-specific models showed little heterogeneity by
      rural-urban community type. Although this analysis found little association
      between youth physical activity and neighborhood characteristics, the findings
      could reflect the crude categorization of the neighborhood amenities (sidewalks,
      parks, recreation centers) and detracting elements (litter, dilapidated housing,
      vandalism) and suggests that simple measurement of the presence of an amenity or
      detracting element is insufficient for determining potential associations with
      reaching minimum levels of physical activity. By exploring neighborhood
      characteristics and features of neighborhood amenities within the context of well
      defined community types, like RUCAs, we can better understand how and why these
      factors contribute to different levels of youth physical activity.

PMID- 23160763
TI  - Youth with special health care needs: transition to adult health care services.
AB  - Transition to adult services for children and youth with special health care
      needs (CYSHCN) has emerged as an important event in the life course of
      individuals with disabilities. Issues that interfere with efficient transition to
      adult health care include the perspectives of stakeholders, age limits on
      pediatric service, complexity of health conditions, a lack of experienced
      healthcare professionals in the adult arena, and health care financing for
      chronic and complex conditions. The purposes of this study were to develop a
      definition of successful transition and to identify determinants that were
      associated with a successful transition. The 2007 Survey of Adult Transition and
      Health dataset was used to select variables to be considered for defining success
      and for identifying predictors of success. The results showed that a small
      percentage of young adults who participated in the 2007 survey had experienced a
      successful transition from their pediatric care. 

PMID- 23160764
TI  - Spreading dynamics of cellular aggregates confined to adhesive bands.
AB  - We examine the spreading of cellular aggregates deposited on adhesive striated
      glass surfaces consisting of 100 MUm large bands alternatively coated with
      fibronectin and with PolyEthyleneGlycol-Poly-L-lysine (PEG-PLL). The aggregates
      spread confined to the adhesive fibronectin bands. A front of cells expands from
      the aggregate at constant velocity. In comparison, the radial spreading of an
      aggregate on the uniform fibronectin coated glass surface obeys a diffusive law.
      We develop a common theoretical model in agreement with our experimental
      observations to describe the apparently disparate spreading kinetics of cellular
      aggregates. These results demonstrate the dominant role of the permeation in the
      expansion of the precursor film of cells around the aggregate.

PMID- 23160765
TI  - Tensile strength and fracture of cemented granular aggregates.
AB  - Cemented granular aggregates include a broad class of geomaterials such as
      sedimentary rocks and some biomaterials such as the wheat endosperm. We present a
      3D lattice element method for the simulation of such materials, modeled as a
      jammed assembly of particles bound together by a matrix partially filling the
      interstitial space. From extensive simulation data, we analyze the mechanical
      properties of aggregates subjected to tensile loading as a function of matrix
      volume fraction and particle-matrix adhesion. We observe a linear elastic
      behavior followed by a brutal failure along a fracture surface. The effective
      stiffness before failure increases almost linearly with the matrix volume
      fraction. We show that the tensile strength of the aggregates increases with both
      the increasing tensile strength at the particle-matrix interface and decreasing
      stress concentration as a function of matrix volume fraction. The proportion of
      broken bonds in the particle phase reveals a range of values of the particle
      matrix adhesion and matrix volume fraction for which the cracks bypass the
      particles and hence no particle damage occurs. This limit is shown to depend on
      the relative toughness of the particle-matrix interface with respect to the
      particles.

PMID- 23160766
TI  - Beyond Saffman-Delbruck approximation: a new regime for 2D diffusion of alpha
      hemolysin complexes in supported lipid bilayer.
AB  - Cell mechanisms are actively modulated by membrane dynamics. We studied the
      dynamics of a first-stage biomimetic system by Fluorescence Recovery After
      Patterned Photobleaching. Using this simple biomimetic system, constituted by
      alpha -hemolysin from Staphylococcus aureus inserted as single heptameric pore or
      complexes of pores in a glass-supported DMPC bilayer, we observed true diffusion
      behavior, with no immobile fraction. We find two situations: i) when incubation
      is shorter than 15 hours, the protein inserts as a heptameric pore and diffuses
      roughly three times more slowly than its host lipid bilayer; ii) incubation
      longer than 15 hours leads to the formation of larger complexes which diffuse
      more slowly. Our results indicate that, while the Saffman-Delbruck model
      adequately describes the diffusion coefficient D for small radii, D of the
      objects decreases as 1/R(2) for the size range explored in this study.
      Additionally, in the presence of inserted proteins, the gel-to-fluid transition
      of the supported bilayer as well as a temperature shift in the gel-to-fluid
      transition are observed.

PMID- 23160767
TI  - Erythropoietin stimulation decreases hepcidin expression through hematopoietic
      activity on bone marrow cells in mice.
AB  - Erythropoiesis-stimulating agents (ESA) are now central to the treatment of renal
      anemia and are associated with improved clinical outcomes. It is well known that
      erythropoietin (EPO) is a key regulator of erythropoiesis through its promotion
      of red blood cell production. In order to investigate the role of ESA on iron
      metabolism, we analyzed the regulation of the iron regulatory hormone hepcidin by
      ESA treatment in a bone marrow transplant model in mouse. After treating C57BL/6
      mice with continuous erythropoietin receptor activator (C.E.R.A.), recombinant
      human epoetin-beta (rhEPO), or recombinant human carbamylated epoetin-beta
      (rhCEPO), we investigated serum hepcidin concentrations and parameters of
      erythropoiesis. Serum hepcidin concentrations after rhEPO treatment were analyzed
      in mice subjected to total body irradiation followed by bone marrow
      transplantation. C.E.R.A. administration caused long-term downregulation of serum
      hepcidin levels. Serum hepcidin levels in rhEPO-treated mice decreased
      significantly, whereas there was no change in rhCEPO-treated mice. The reduction
      in circulating hepcidin levels after rhEPO administration was not observed in
      irradiated mice. Finally, bone marrow transplantation recovered the response to
      rhEPO administration that downregulates hepcidin concentration in irradiated
      mice. These results indicate that ESA treatment downregulates serum hepcidin
      concentrations, mainly by indirect mechanisms affecting hematopoietic activity in
      bone marrow cells.

PMID- 23160768
TI  - Extravascular lung water and its association with weight, height, age, and
      gender: a study in intensive care unit patients.
AB  - PURPOSE: With regard to large inter-individual variability of height, body weight
      (BW), and age, several hemodynamic parameters are adjusted for biometric data.
      This also applies to extravascular lung water (EVLW), which traditionally was
      indexed to actual BW (BW-act) resulting in EVLW-index (EVLWI; i.e., EVLWI-act).
      Since indexation to BW-act might inappropriately diminish EVLWI-act in obese
      patients, the indexation has been changed to predicted BW (BW-pred) resulting in
      EVLWI-pred. BW-pred is a weight estimation formula calculated from height and
      gender that has not been derived from population-based data. The aim of the study
      was to investigate the independent association of biometric data with EVLW.
      METHODS: We analyzed a hemodynamic monitoring database including 3,691
      transpulmonary thermodilution-derived EVLW measurements (234 consecutive
      patients; intensive care unit of a university hospital). We performed univariate
      and multivariate analyses regarding the association of biometric data with the
      first EVLW measurement and the mean EVLW value of each patient. RESULTS: In
      univariate analysis, the first EVLW significantly correlated with height (r =
      0.254; p < 0.001), but neither with age nor BW-act. Similar findings were made in
      the analysis of the patients' EVLW means of all measurements ("one point per
      patient"). In multivariate analysis (primary endpoint), including BW-act, height,
      age, and gender, only height was independently associated with EVLW, with each
      centimeter of height increasing the first measurement of EVLW by 6.882 mL (p <
      0.001) and mean EVLW by 6.727 mL (p < 0.001). CONCLUSIONS: Height is the only
      biometric parameter independently associated with the first and mean EVLW. In
      adult patients, EVLW should be indexed to height.

PMID- 23160771
TI  - Pressure-guided positioning of bicaval dual-lumen catheters for venovenous
      extracorporeal gas exchange.
AB  - PURPOSE: Bicaval dual-lumen catheters allow for single-site cannulation
      venovenous extracorporeal gas exchange and facilitate early mobilization of
      patients. Using these catheters blood is drained from the superior and inferior
      venae cavae, pumped through a respiratory membrane, and returned into the right
      atrium. The insertion of these catheters is challenging as their correct
      positioning is fundamental to reduce recirculation and avoid severe
      complications. We describe here a new technique for the positioning of bicaval
      dual-lumen catheters. MATERIALS AND METHODS: The right internal jugular vein was
      percutaneously cannulated in nine sheep. The distance between skin and tricuspid
      valve was measured from the point of pressure change in the waveform of a Swan
      Ganz catheter being retracted from the right ventricle into the right atrium. The
      atrium-tricuspid valve-ventricle axis was determined by observing the
      fluctuations of the tip of the Swan-Ganz entering the ventricle during
      fluoroscopy. A bicaval dual-lumen catheter was placed on the basis of these
      evaluations and connected to an extracorporeal respiratory support system.
      RESULTS: The position of the catheter was verified at necropsy approximately 18 h
      after insertion. In all cases the catheter was correctly placed, with the central
      port situated in front of the tricuspid valve. CONCLUSIONS: The described
      technique may help to position bicaval dual-lumen catheters for venovenous
      extracorporeal gas exchange without the use of transesophageal echocardiography
      or contrast media during fluoroscopy.

PMID- 23160770
TI  - Intubation-related tracheal ischemic lesions: incidence, risk factors, and
      outcome.
AB  - PURPOSE: To determine incidence, risk factors and outcome of tracheal ischemic
      lesions related to intubation. METHODS: Planned post hoc analysis using patients
      from a previous randomized controlled study. Fiberoptic tracheoscopy was
      performed during the 24 h following extubation. In patients with >2 ischemic
      lesions, ulcer or tracheal rupture, fiberoptic tracheoscopy was repeated 2 weeks
      after the last extubation. Tracheal ischemic lesions were predefined based on a
      quantitative score. RESULTS: Ninety-six adult patients were included in this
      study. Eighty (83 %) patients had at least one tracheal ischemic lesion. Thirty
      seven (38 %) patients had a tracheal ischemia score > median score (5; IQ 1, 7).
      The most common tracheal ischemic lesion was ischemia (68 %), followed by
      hyperemia (54 %), ulcer (10 %), and tracheal rupture (1 %). Univariate analysis
      identified duration of neuromuscular-blocking agent use, overinflation of
      tracheal cuff (>30 cmH2O), percentage of P cuff determination >30 cmH2O, duration
      of assist-control ventilation, and plateau pressure as risk factors for having a
      tracheal ischemia score >5. Duration of assist-control mechanical ventilation was
      the only factor independently associated with tracheal ischemia score >5 [OR (95
      % CI) 1.10 per hour (1.02-1.20)]. A fiberoptic tracheoscopy was performed 2 weeks
      after extubation in 22 patients. This examination was normal in all patients,
      except the one with tracheal rupture who had marked improvement. CONCLUSION:
      Tracheal ischemic lesions are common in intubated, critically ill patients.
      Duration of assist-control mechanical ventilation through a tracheal tube is the
      only independent risk factor. These lesions healed in the majority of patients 2
      weeks after extubation.

PMID- 23160769
TI  - Predicting mortality risk in patients undergoing venovenous ECMO for ARDS due to
      influenza A (H1N1) pneumonia: the ECMOnet score.
AB  - PURPOSE: The decision to start venovenous extracorporeal membrane oxygenation (VV
      ECMO) is commonly based on the severity of respiratory failure, with little
      consideration of the extrapulmonary organ function. The aim of the study was to
      identify predictors of mortality and to develop a score allowing a better
      stratification of patients at the time of VV ECMO initiation. METHODS: This was a
      prospective multicenter cohort study on 60 patients with influenza A (H1N1)
      associated respiratory distress syndrome participating in the Italian ECMOnet
      data set in the 2009 pandemic. Criteria for ECMO institution were standardized
      according to national guidelines. RESULTS: The survival rate in patients treated
      with ECMO was 68 %. Significant predictors of death before ECMO institution by
      multivariate analysis were hospital length of stay before ECMO institution (OR =
      1.52, 95 % CI 1.12-2.07, p = 0.008); bilirubin (OR = 2.32, 95 % CI 1.52-3.52, p <
      0.001), creatinine (OR = 7.38, 95 % CI 1.43-38.11, p = 0.02) and hematocrit
      values (OR = 0.82, 95 % CI 0.72-0.94, p = 0.006); and mean arterial pressure (OR
      = 0.92, 95 % CI 0.88-0.97, p < 0.001). The ECMOnet score was developed based on
      these variables, with a score of 4.5 being the most appropriate cutoff for
      mortality risk prediction. The high accuracy of the ECMOnet score was further
      confirmed by ROC analysis (c = 0.857, 95 % CI 0.754-0.959, p < 0.001) and by an
      independent external validation analysis (c = 0.694, 95 % CI 0.562-0.826, p =
      0.004). CONCLUSIONS: Mortality risk for patients receiving VV ECMO is correlated
      to the extrapulmonary organ function at the time of ECMO initiation. The ECMOnet
      score is a tool for the evaluation of the appropriateness and timing of VV ECMO
      in acute lung failure.

PMID- 23160772
TI  - Rising serum sodium levels are associated with a concurrent development of
      metabolic alkalosis in critically ill patients.
AB  - PURPOSE: Changes in electrolyte homeostasis are important causes of acid-base
      disorders. While the effects of chloride are well studied, only little is known
      of the potential contributions of sodium to metabolic acid-base state. Thus, we
      investigated the effects of intensive care unit (ICU)-acquired hypernatremia on
      acid-base state. METHODS: We included critically ill patients who developed
      hypernatremia, defined as a serum sodium concentration exceeding 149 mmol/L,
      after ICU admission in this retrospective study. Data on electrolyte and acid
      base state in all included patients were gathered in order to analyze the effects
      of hypernatremia on metabolic acid-base state by use of the physical-chemical
      approach. RESULTS: A total of 51 patients were included in the study. The time of
      rising serum sodium and hypernatremia was accompanied by metabolic alkalosis. A
      transient increase in total base excess (standard base excess from 0.1 to 5.5
      mmol/L) paralleled by a transient increase in the base excess due to sodium (base
      excess sodium from 0.7 to 4.1 mmol/L) could be observed. The other determinants
      of metabolic acid-base state remained stable. The increase in base excess was
      accompanied by a slight increase in overall pH (from 7.392 to 7.429, standard
      base excess from 0.1 to 5.5 mmol/L). CONCLUSIONS: Hypernatremia is accompanied by
      metabolic alkalosis and an increase in pH. Given the high prevalence of
      hypernatremia, especially in critically ill patients, hypernatremic alkalosis
      should be part of the differential diagnosis of metabolic acid-base disorders.

PMID- 23160773
TI  - (Bio-)remediation of VCHC contaminants in a Technosol under unsaturated
      conditions.
AB  - The remediation of dense non-aqueous phase liquids has always been a concern of
      both public and scientific interest groups. In this research work a modified
      physical concept of (bio)remediation of a volatile chlorinated hydrocarbon (VCHC)
      contamination was elaborated under laboratory conditions and modeled with HYDRUS
      2D. In field dechlorination is influenced by both physicochemical and hydraulic
      properties of the substrate, e.g. texture, pore size distribution, pore liquid
      characteristics, e.g. viscosity, pH, surface tension, and dependent on the degree
      of saturation of the vadose zone. Undisturbed soil cores (100 cm3) were sampled
      from a Spolic Technosol. Considering hydraulic properties and functions,
      unsaturated percolation was performed with vertically and horizontally structured
      samples. VCHC concentrations were calculated prior, during, and after each
      percolation cycle. According to laboratory findings, microemulsion showed the
      most efficient results with regard to flow behavior in the unsaturated porous
      media and its accessibility for bacteria as nutrient. The efficiency of VCHC
      remediation could be increased by the application of a modified pump-and-treat
      system: the injection of bacteria Dehalococcoides ethanogenes with microemulsion,
      and extraction at a constant matric potential level of -6 kPa. Achieved data was
      used for HYDRUS-2D simulations, modeling in situ conditions, demonstrating the
      practical relevance (field scale) of performed unsaturated percolation (core
      scale), and in order to exclude capillary barrier effects.

PMID- 23160774
TI  - From muscle wasting to sarcopenia and myopenia: update 2012.
AB  - Human muscle undergoes constant changes. After about age 50, muscle mass
      decreases at an annual rate of 1-2 %. Muscle strength declines by 1.5 % between
      ages 50 and 60 and by 3 % thereafter. The reasons for these changes include
      denervation of motor units and a net conversion of fast type II muscle fibers
      into slow type I fibers with resulting loss in muscle power necessary for
      activities of daily living. In addition, lipids are deposited in the muscle, but
      these changes do not usually lead to a loss in body weight. Once muscle mass in
      elderly subjects falls below 2 standard deviations of the mean of a young control
      cohort and the gait speed falls below 0.8 m/s, a clinical diagnosis of sarcopenia
      can be reached. Assessment of muscle strength using tests such as the short
      physical performance battery test, the timed get-up-and-go test, or the stair
      climb power test may also be helpful in establishing the diagnosis. Serum markers
      may be useful when sarcopenia presence is suspected and may prompt further
      investigations. Indeed, sarcopenia is one of the four main reasons for loss of
      muscle mass. On average, it is estimated that 5-13 % of elderly people aged 60-70
      years are affected by sarcopenia. The numbers increase to 11-50 % for those aged
      80 or above. Sarcopenia may lead to frailty, but not all patients with sarcopenia
      are frail-sarcopenia is about twice as common as frailty. Several studies have
      shown that the risk of falls is significantly elevated in subjects with reduced
      muscle strength. Treatment of sarcopenia remains challenging, but promising
      results have been obtained using progressive resistance training, testosterone,
      estrogens, growth hormone, vitamin D, and angiotensin-converting enzyme
      inhibitors. Interesting nutritional interventions include high-caloric
      nutritional supplements and essential amino acids that support muscle fiber
      synthesis.

PMID- 23160776
TI  - Guideline for Technical Quality Assurance (TQA) of ultrasound devices (B-Mode)-
      version 1.0 (July 2012): EFSUMB Technical Quality Assurance Group--US-TQA/B.
AB  - The Technical Quality Assurance group was initiated by the EFSUMB Board in 2007
      and met firstly in 2008 to discuss and evaluate methods and procedures published
      for performing technical quality assurance for diagnostic ultrasound devices. It
      is the aim of this group of experts to advise the EFSUMB Board of effective and
      efficacious methods for routine use and to make recommendations regarding the
      technical aspects of EFSUMB by-law 9, parts 11.6. & 11.7. The group's work
      focused on new developments and related European projects to establish a common
      guideline. There is a great need of a well established protocol and dedicated
      processing software for the performance testing of medical ultrasound equipment.
      The measurements should be user independent as much as physically possible. Only
      if these goals are achieved in an international (firstly European) context, the
      optimal quality of ultrasound imaging can be offered and maintained to the
      medical community. This guideline aims to offer and summarize suitable procedures
      and evaluation processes to lend support for an optimal Technical Quality
      Assurance (TQA) scheme. The content of this guideline was presented to the EFSUMB
      Board of Directors (delegates) and approved by the EFSUMB Executive Board (ExB)
      at the regular meeting during EUROSON 2012 in Madrid April 2012.

PMID- 23160775
TI  - Research on cachexia, sarcopenia and skeletal muscle in cardiology.
AB  - BACKGROUND: The awareness of cardiac cachexia, i.e. involuntary weight loss in
      patients with underlying cardiovascular disease, has increased over the last two
      decades. METHODS AND RESULTS: This mini-review looks at recent research in the
      cardiovascular literature that is relevant to the areas of interest of the
      Journal of Cachexia, Sarcopenia and Muscle. It identifies significant research in
      the last 3 years on the obesity paradox, the causes and effects of skeletal
      muscle wasting, animal models of cachexia and emerging treatment ideas in cardiac
      cachexia. CONCLUSIONS: Assuming a similar literature in the fields of cancer,
      chronic obstructive pulmonary disease, chronic renal failure and chronic liver
      failure, the emergence of cachexia as a vibrant area of clinical and experimental
      research seems assured.

PMID- 23160777
TI  - Single session of Nd:YAG laser intracanal irradiation neutralizes endotoxin in
      dental root dentin.
AB  - Endotoxins released in the dental root by Gram-negative microorganisms can be
      neutralized by calcium hydroxide, when this medication is applied inside the root
      canal for at least seven days. However, several clinical situations demand faster
      root canal decontamination. Thus, for faster endotoxin neutralization,
      endodontists are seeking additional treatments. The in vitro study tested whether
      or not intracanal Nd:YAG laser irradiation would be able to neutralize endotoxin
      within the human dental root canal in a single session. Twenty-four human teeth
      with one root were mounted between two chambers. After conventional endodontic
      treatment, root canals were contaminated with Escherichia coli endotoxin. Then
      they were irradiated or not (controls) in contact mode with an Nd:YAG laser (1.5
      W, 15 Hz, 100 mJ and pulse fluency of 124  J/cm2). The endotoxin activity was
      measured using the limulus lysate technique and data were statistically compared
      (p<=0.05). The concentration of active endotoxin measured in the negative control
      group was significantly lower than that of the positive control group (p=0.04).
      The concentrations of endotoxin in both irradiated groups were significantly
      lower than that of the positive control group (p=0.027) and similar to that of
      negative control group (p=0.20). A single session of intracanal Nd:YAG laser
      irradiation is able to neutralize endotoxin in the dental root tissues.

PMID- 23160780
TI  - Lifestyle factors, autoimmune disease and family history in prognosis of non
      hodgkin lymphoma overall and subtypes.
AB  - Lifestyle factors and medical history are known to influence risk of non-Hodgkin
      lymphoma (NHL). Whether these factors affect the prognosis of NHL, especially its
      subtypes, is unclear. To investigate this, the association between these factors
      and all-cause and lymphoma-related mortality was assessed in a population-based
      cohort of 1,523 Swedish NHL patients included in the Scandinavian Lymphoma
      Etiology study in 1999-2002. Participants contributed time from NHL diagnosis
      until death or October 1, 2010, with virtually complete follow-up through linkage
      to the Swedish Cause of Death Register. Hazard ratios (HR) and 95% confidence
      intervals (CI) were estimated using stratified and multivariable-adjusted Cox
      regression models. During a median follow-up of 8.8 years, 670 patients (44%)
      died, with the majority of deaths attributed to lymphoma (86%). Current versus
      never smoking at diagnosis was associated with increased rate of all-cause death
      for all NHL (HR = 1.5, 1.2-1.8) and diffuse large B-cell lymphoma (HR = 1.8, 1.2
      2.7). Low educational level (HR = 1.3, 1.1-1.7, <9 vs. >12 years) and NHL risk
      associated autoimmune disease (HR = 1.4, 1.0-1.8) were associated with death for
      all NHL combined. However, evidence of an association with lymphoma-related death
      was limited. Body mass index, recent sunbathing and family history of
      hematopoietic malignancy were not consistently associated with death after NHL or
      its specific subtypes. These results add to the evidence that cigarette smoking,
      socioeconomic status and certain autoimmune diseases affect survival after NHL.
      Further investigations are needed to determine how these factors should be
      incorporated into clinical prognostic assessment.

PMID- 23160782
TI  - The effect of complete radial lateral meniscus posterior root tear on the knee
      contact mechanics: a finite element analysis.
AB  - BACKGROUND: In recent years, with technological advances in arthroscopy and
      magnetic resonance imaging and improved biomechanical studies of the meniscus,
      there has been some progress in the diagnosis and treatment of injuries to the
      roots of the meniscus. However, the biomechanical effect of posterior lateral
      meniscus root tears on the knee has not yet become clear. The purpose of this
      study was to determine the effect of a complete radial posterior lateral meniscus
      root tear on the knee contact mechanics and the function of the posterior
      meniscofemoral ligament on the knee with tear in the posterior root of lateral
      meniscus. METHODS: A finite element model of the knee was developed to simulate
      different cases for intact knee, a complete radial posterior lateral meniscus
      root tear, a complete radial posterior lateral meniscus root tear with posterior
      meniscofemoral ligament deficiency, and total meniscectomy of the lateral
      meniscus. A compressive load of 1000 N was applied in all cases to calculate
      contact areas, contact pressure, and meniscal displacements. RESULTS: The
      complete radial posterior lateral meniscus root tear decreased the contact area
      and increased the contact pressure on the lateral compartment under compressive
      load. We also found a decreased contact area and increased contact pressure in
      the medial compartment, but it was not obvious compared to the lateral
      compartment. The lateral meniscus was radially displaced by compressive load
      after a complete radial posterior lateral meniscus root tear, and the
      displacement took place mainly in the body and posterior horn of lateral
      meniscus. There were further decrease in contact area and increases in contact
      pressure and raidial displacement of the lateral meniscus in the case of the
      complete posterior lateral meniscus root tear in combination with posterior
      meniscofemoral ligament deficiency. CONCLUSIONS: Complete radial posterior
      lateral meniscus root tear is not functionally equivalent to total meniscectomy.
      The posterior root torn lateral meniscus continues to provide some load
      transmission and distribution functions across the joint. The posterior
      meniscofemoral ligament prevents excessive radial displacement of the posterior
      root torn lateral meniscus and assists the torn lateral meniscus in transmitting
      a certain amount of stress in the lateral compartment.

PMID- 23160781
TI  - MxA transcripts with distinct first exons and modulation of gene expression
      levels by single-nucleotide polymorphisms in human bronchial epithelial cells.
AB  - Myxovirus resistance A (MxA) is a major interferon (IFN)-inducible antiviral
      protein. Promoter single-nucleotide polymorphisms (SNPs) of MxA near the IFN
      stimulated response element (ISRE) have been frequently associated with various
      viral diseases, including emerging respiratory infections. We investigated the
      expression profile of MxA transcripts with distinct first exons in human
      bronchial epithelial cells. For primary culture, the bronchial epithelium was
      isolated from lung tissues with different genotypes, and total RNA was subjected
      to real-time reverse transcription polymerase chain reaction. The previously
      reported MxA transcript (T1) and a recently registered transcript with a distinct
      5' first exon (T0) were identified. IFN-beta and polyinosinic-polycytidylic acid
      induced approximately 100-fold higher expression of the T1 transcript than that
      of the T0 transcript, which also had a potential ISRE motif near its
      transcription start site. Even without inducers, the T1 transcript accounted for
      approximately two thirds of the total expression of MxA, levels of which were
      significantly associated with its promoter and exon 1 SNPs (rs17000900,
      rs2071430, and rs464138). Our results suggest that MxA observed in respiratory
      viral infections is possibly dominated by the T1 transcript and partly influenced
      by relevant 5' SNPs.

PMID- 23160783
TI  - Prognosis in women with interval breast cancer: population based observational
      cohort study.
AB  - OBJECTIVE: To compare the prognosis in women with interval breast cancer (cancer
      detected after a normal screening mammogram and before the next scheduled
      mammogram) with breast cancer detected among women not yet invited to mammography
      screening (non-screened). DESIGN: Population based observational study. SETTING:
      Norwegian breast cancer screening programme, implemented in different counties
      from 1996 to 2005. PARTICIPANTS: 7116 women with a diagnosis of breast cancer at
      age 50 to 72 years; 1816 had interval breast cancer and 5300 had a diagnosis of
      breast cancer but had not yet been invited to screening. MAIN OUTCOME MEASURES:
      Characteristics of the breast tumours, and survival of the women using Kaplan
      Meier curves and multivariable Cox proportional hazard models. RESULTS: Although
      interval cancers on average were slightly larger than the cancers in women not
      invited to screening, the histological type or status of axillary lymph nodes did
      not differ noticeably between the two groups. Among interval cancers, there were
      no appreciable trends in size, nodal status, grade, or hormone receptor
      positivity associated with time since the last normal mammogram as a marker of
      growth rate. After 10 years of follow-up, the survival rates were 79.1% (95%
      confidence interval 75.4% to 82.3%) among women with interval cancers and 76.8%
      (75.3% to 78.2%) among women in the non-screened cancer group (hazard ratio 0.98,
      95% confidence interval 0.84 to 1.15; P=0.53). Analyses stratified by time since
      last normal mammogram, age at diagnosis, or screening round showed similar
      results. CONCLUSION: The prognosis of women with interval breast cancers was the
      same as that of women with breast cancers diagnosed without mammography
      screening.

PMID- 23160784
TI  - A patient with longstanding type 1 diabetes and a swollen, warm, and red foot.

PMID- 23160785
TI  - Metal-on-metal hip prostheses: where are we now?

PMID- 23160786
TI  - The peeved middle.

PMID- 23160787
TI  - States get their say on health: post-election round up.

PMID- 23160788
TI  - Quantification of brain glucose metabolism by 18F-FDG PET with real-time arterial
      and image-derived input function in mice.
AB  - Kinetic modeling of PET data derived from mouse models remains hampered by the
      technical inaccessibility of an accurate input function (IF). In this work, we
      tested the feasibility of IF measurement with an arteriovenous shunt and a
      coincidence counter in mice and compared the method with an image-derived IF
      (IDIF) obtained by ensemble-learning independent component analysis of the heart
      region. METHODS: (18)F-FDG brain kinetics were quantified in 2 mouse strains, CD1
      and C57BL/6, using the standard 2-tissue-compartment model. Fits obtained with
      the 2 IFs were compared regarding their goodness of fit as assessed by the
      residuals, fit parameter SD, and Bland-Altman analysis. RESULTS: On average,
      cerebral glucose metabolic rate was 10% higher for IDIF-based quantification. The
      precision of model parameter fitting was significantly higher using the shunt
      based IF, rendering the quantification of single process rate constants feasible.
      CONCLUSION: We demonstrated that the arterial IF can be measured in mice with a
      femoral arteriovenous shunt. This technique resulted in higher precision for
      kinetic modeling parameters than did use of the IDIF. However, for longitudinal
      or high-throughput studies, the use of a minimally invasive IDIF based on
      ensemble-learning independent component analysis represents a suitable
      alternative.

PMID- 23160789
TI  - Imaging changes in synaptic acetylcholine availability in living human subjects.
AB  - In vivo estimation of beta(2)-nicotinic acetylcholine receptor availability with
      molecular neuroimaging is complicated by competition between the endogenous
      neurotransmitter acetylcholine and the radioligand (123)I-3-[2(S)-2
      azetidinylmethoxy]pyridine ((123)I-5-IA). We examined whether binding of (123)I-5
      IA is sensitive to increases in extracellular levels of acetylcholine in humans,
      as suggested in nonhuman primates. METHODS: Six healthy subjects (31 +/- 4 y)
      participated in a (123)I-5-IA SPECT study. After baseline scans, physostigmine (1
      1.5 mg) was administered intravenously over 60 min, and 9 additional scans were
      obtained. RESULTS: We observed a significant reduction in the total volume of
      distribution after physostigmine administration (29% +/- 17% in the cortex, 19%
      +/- 15% in the thalamus, 19% +/- 15% in the striatum, and 36% +/- 30% in the
      cerebellum; P < 0.05). This reduction reflected a combination of a region
      specific 7%-16% decrease in tissue concentration of tracer and a 9% increase in
      plasma parent concentration. CONCLUSION: These data suggest that increases in
      acetylcholine compete with (123)I-5-IA for binding to beta(2)-nicotinic
      acetylcholine receptor. Additional validation of this paradigm is warranted, but
      it may be used to interrogate changes in extracellular acetylcholine.

PMID- 23160790
TI  - Recent advances in the molecular imaging of programmed cell death: Part II--non
      probe-based MRI, ultrasound, and optical clinical imaging techniques.
AB  - There is much that can be done to detect apoptosis and other forms of cell death
      with existing clinical modalities including ultrasound, MRI, and optical imaging
      without the need for current or new intravenous contrast agents. We will discuss
      how these widely available imaging technologies can readily be applied to the
      imaging of apoptosis in patients undergoing chemotherapy or radiation treatment.
      The limiting factor of course is the lack of knowledge of the optimal times after
      the start of treatment for the most accurate assessment of apoptosis and necrosis
      with each modality and specific technique. It is hoped that imaging studies that
      systematically look at treatment response can soon be performed to address these
      issues.

PMID- 23160791
TI  - Upregulation of CBLL1 in rat brain cortex after lipopolysaccharide treated.
AB  - CBLL1 (Casitas B-lineage lymphoma-transforming sequence-like protein 1) also
      known as Hakai, was originally identified as an E3 ubiquitin-ligase for the E
      cadherin complex. Recent data have provided evidences for novel biological
      functional role of CBLL1 during tumor progression and other diseases. However,
      its distribution and function in the central nervous system (CNS) remains
      unclear. In this study, we found CBLL1 was significant up-regulation in cerebral
      cortex after LPS administration and immunofluorescent labeling indicated that
      CBLL1 was localized striking in the neurons. We also investigated co-staining of
      CBLL1 and active-caspase-3 and cyclin D1 in the cerebral cortex following LPS
      administration. Based on our data, we speculated that CBLL1 might play an
      important role in neuronal apoptosis following LPS administration and might
      provide a basis for the further study on its role in cell cycle re-entry in
      neuroinflammation in CNS.

PMID- 23160792
TI  - Assessment of voluntary exercise behavior and active video gaming among
      adolescent and young adult patients during hematopoietic stem cell
      transplantation.
AB  - This pilot study sought to examine the exercise behavior and preferences among
      adolescent and young adult (AYA) hematopoietic stem cell transplant (HSCT)
      recipients. Eighteen patients aged 19 to 25 years were recruited to engage in
      unsupervised exercise activities lasting at least 60 minutes/week during
      hospitalization for HSCT. Enrolled patients had access to standard exercise
      activities (walking, resistance training, and basketball) and active video gaming
      equipment. Physical function (6-Minute Walk Test and Timed-Up-and-Go test) and
      quality of life (Behavioral, Affective, and Somatic Experiences Scale) were
      assessed at different time points during admission. Participants exercised an
      average of 76% of the days during admission and spent an average of 36.5 minutes
      per day exercising. The Nintendo Wii was the preferred active video gaming
      equipment, but standard exercises accounted for 73% of all exercise time. Neither
      functional capacity nor quality of life improved. Results suggest that AYAs
      voluntarily exercise during HSCT admission, prefer to use standard exercise
      activities, and may require supervision in order to derive maximum benefits from
      their efforts. These results provide guidance for developing rehabilitation
      interventions for AYA HSCT recipients.

PMID- 23160793
TI  - Clinical practice implications of immunizations after pediatric bone marrow
      transplant: a literature review.
AB  - The number of pediatric bone marrow transplants is increasing for malignant and
      nonmalignant diseases. The number of survivors is also increasing, and their long
      term health and protection from infection is increasingly important. To prevent
      infections, it is standard practice to re-immunize pediatric patients after bone
      marrow transplant (BMT) using the Centers for Disease Control and Prevention
      immunization guidelines; however, surveys in the United States and other parts of
      the world indicate that many BMT patients do not receive all the recommended
      immunizations. A literature review was conducted to identify research based on
      evidence for immunization following BMT and to recognize barriers to the process.
      Also, the immunization clinical guidelines from 2000 and 2011 for patients
      following BMT were compared and an updated clinical protocol and immunization
      schedule was developed to reflect the current evidence, encourage a change in
      practice, and discourage fragmented care.

PMID- 23160794
TI  - New cholestane glycosides and sterols from the underground parts of Chamaelirium
      luteum and their cytotoxic activity.
AB  - Six new cholestane glycosides (1, 5, 6, 10, 12, and 13) and two new sterols (9
      and 11), along with five known compounds (2-4, 7, and 8), were isolated from the
      underground parts of Chamaelirium luteum (Liliaceae). The structures of these new
      compounds were determined by spectroscopic analysis and the results of hydrolytic
      cleavage. The isolated compounds and aglycones were evaluated for their cytotoxic
      activity against HL-60 human leukemia cells. Compounds 6a, 10a, 12a, 13, and 13a
      were cytotoxic to HL-60 cells, with IC50 values of 12.8, 9.8, 15.3, 6.2, and 10.2
      uM, respectively.

PMID- 23160795
TI  - Personalized decision support in type 2 diabetes mellitus: current evidence and
      future directions.
AB  - The management of type 2 diabetes comprises a complex series of medical decisions
      regarding goals of care, self-care behaviors, and medical treatments. The quality
      of these medical decisions is critical to determining whether an individual
      diabetes patient is treated appropriately, overtreated, or undertreated. It is
      hypothesized that the quality of these medical decisions can be enhanced by
      personalized decision support tools that summarize patient clinical
      characteristics, treatment preferences, and ancillary data at the point of care.
      We describe the current state of personalized diabetes decision support on the
      basis of 13 recently described tools. Three tools provided support for
      personalized decisions based on preferences, while the remaining 10 provided
      support for treatment decisions designed to achieve standard diabetes goals. For
      the tools that supported personalized decisions, patient participation in medical
      decisions improved. Future decision support tools must be designed to account for
      both clinical characteristics and patient preferences.

PMID- 23160796
TI  - Azimuthal sound localization in the European starling (Sturnus vulgaris): II.
      Psychophysical results.
AB  - Small songbirds have a difficult analysis problem: their head is small compared
      to the wavelengths of sounds used for communication providing only small
      interaural time and level differences. Klump and Larsen (1992) measured the
      physical binaural cues in the European starling (Sturnus vulgaris) that allow the
      comparison of acoustical cues and perception. We determined the starling's
      minimum audible angle (MAA) in an operant Go/NoGo procedure for different
      spectral and temporal stimulus conditions. The MAA for broadband noise with
      closed-loop localization reached 17 degrees , while the starling's MAA for open
      loop localization of broadband noise reached 29 degrees . No substantial
      difference between open-loop and closed-loop localization was found in 2 kHz pure
      tones. The closed-loop MAA improved from 26 degrees  to 19 degrees  with an
      increase in pure tone frequency from 1 to 4 kHz. This finding is in line with the
      physical cues available. While the starlings can only make use of interaural time
      difference cues at lower frequencies (e.g., 1 and 2 kHz), additional interaural
      level difference cues become available at higher frequencies (e.g., 4 kHz or
      higher, Klump and Larsen 1992). An improvement of the starling's MAA with an
      increasing number of standard stimulus presentations prior to the test stimulus
      has important implications for determining relative (MAA) localization
      thresholds.

PMID- 23160797
TI  - Pre-existing sensory biases in the spectral domain in frogs: empirical results
      and methodological considerations.
AB  - In many species of anurans, advertisement calls excite only one of the two inner
      ear organs. One prediction of the pre-existing bias hypothesis is that signal
      innovations that additionally excite the "untapped" organ will be more
      behaviorally effective than normal calls. However, recent studies have shown that
      females of three species with single-peaked calls that stimulate only the basilar
      papilla (BP) preferred single-peaked synthetic calls with a frequency typical of
      conspecific calls to two-peaked calls that also stimulated the amphibian papilla
      (AP). We report that in spring peepers (Pseudacris crucifer) that also produce
      single-peaked calls, females did not show a preference in choices between single
      peaked and two-peaked synthetic calls. Thus, the addition of energy exciting the
      AP had a neutral effect on signal attractiveness. Together, these results are
      unsupportive of the pre-existing bias hypothesis. An alternative hypothesis is
      that positive fitness consequences of responding to sounds providing
      extraordinary spectral stimulation are required for a novel call to become
      established as a mate-attracting signal. Testing these ideas requires a
      taxonomically broader examination of responses to sounds with novel spectral
      complexity, and attention to some methodological details will improve the
      comparability of such studies.

PMID- 23160798
TI  - Reactions of copper macrocycles with antioxidants and HOCl: potential for
      biological redox sensing.
AB  - A series of simple copper N(2)S(2) macrocycles were examined for their potential
      as biological redox sensors, following previous characterization of their redox
      potentials and crystal structures. The divalent species were reduced by
      glutathione or ascorbate at a biologically relevant pH in aqueous buffer. A less
      efficient reduction was also achieved by vitamin E in DMSO. Oxidation of the
      corresponding univalent copper species by sodium hypochlorite resulted in only
      partial (~65 %) recovery of the divalent form. This was concluded to be due to
      competition between metal oxidation and ligand oxidation, which is believed to
      contribute to macrocycle demetallation. Electrospray mass spectrometry confirmed
      that ligand oxidation had occurred. Moreover, the macrocyclic complexes could be
      demetallated by incubation with EDTA and bovine serum albumin, demonstrating that
      they would be inappropriate for use in biological systems. The susceptibility to
      oxidation and demetallation was hypothesized to be due to oxidation of the
      secondary amines. Consequently these were modified to incorporate additional
      oxygen donor atoms. This modification led to greater resistance to demetallation
      and ligand oxidation, providing a better platform for further development of
      copper macrocycles as redox sensors for use in biological systems.

PMID- 23160799
TI  - Knockdown of dishevelled-1 attenuates cyclosporine A-induced apoptosis in H9c2
      cardiomyoblast cells.
AB  - Cyclosporine (CsA) has become a mainstay for immune suppression of organ
      transplants. It is known that patients receiving CsA manifest increased growth of
      aggressive cardiotoxicity. We have demonstrated that CsA induces myocardium cell
      apoptosis in vivo and vitro. Recently, dishevelled-1 (Dvl-1) protein, which is a
      cytoplasmic mediator of Wnt/beta-catenin signaling, was explored in cardiac
      diseases. However, whether Dvl-1 is involved in CsA-induced apoptosis remains to
      be determined. The aim of this study was to explore the role of Dvl-1 in CsA
      induced apoptosis in H9c2 cardiomyoblast cells and to investigate the role of the
      Wnt/beta-catenin signaling cascade in this progress. H9c2 cells were treated with
      CsA in dose and time-dependent manners. We found that the appropriate
      concentrations and time-points of CsA-induced the expression of Dvl-1 and
      subsequent up-regulation of beta-catenin and c-Myc, which is consistent with
      previously demonstrated concentrations and time-points when H9c2 cells apoptosis
      occurred. Then, cells were transfected with small interfering RNA (siRNA) against
      Dvl-1 and stimulated with previously demonstrated concentration of CsA. Dvl-1
      down-regulation decreased the apoptotic rate, caspase-3 activity, and the Bax/Bcl
      2 ratio in H9c2 cells treated with CsA. Furthermore, knocking down the expression
      of Dvl-1 partially suppressed the activity of the Wnt/beta-catenin pathway.
      Moreover, we further deleted the downstream member beta-catenin by specific
      siRNA, and found that CsA-induced the Bax/Bcl-2 ratio and the expression of c
      Myc, which were attenuated. Our results are the first to unveil this novel aspect
      of Dvl-1 signaling. In addition, these data provide insight into the pathogenesis
      and the therapeutic strategies of CsA-induced myocardial injury.

PMID- 23160800
TI  - Interleukin-8 stimulates progesterone production via the MEK pathway in ovarian
      theca cells.
AB  - Interleukin 8 (IL-8) is a chemoattractant associated with ovulation in the
      mammalian ovary. This chemokine is also involved in the recruitment and
      activation of neutrophils. Using bovine tissue, we examined the possible role of
      IL-8 in steroid production by theca cells of the large ovarian follicles. IL-8
      promoted progesterone production and stimulated StAR expression in cultured theca
      cells. The inhibitor of p38 did not disturb the P4 production and StAR expression
      in IL-8-treated theca cells. On the other hand, the inhibitor of MEK disturbed
      the P4 production and expression of StAR in theca cells treated with IL-8. These
      results suggest that IL-8 is associated with progesterone production in bovine
      theca cells via the MEK pathway.

PMID- 23160801
TI  - Oxidative stress in coronary artery disease: epigenetic perspective.
AB  - The association between oxidative stress and coronary artery disease (CAD) is
      well documented. However, the role of epigenetic factors contributing to
      oxidative stress is relatively unexplored. In this study, we aimed to explore the
      impact of DNA methylation profile in BCL2/E1B adenovirus interacting protein 3
      (BNIP3), extracellular superoxide dismutase (EC-SOD) and glutathione-S
      transferase P1 (GSTP1) on the oxidative stress in CAD. Further, the contribution
      of folate pathway genetic polymorphisms in regulating epigenome was elucidated.
      The expression of BNIP3, EC-SOD, and GSTP1 were studied by using Maxima@SYBR
      green based real-time qPCR approach in peripheral blood samples. Combined
      bisulfite restriction analysis and methylation-specific PCR were used to study
      promoter CpG island methylation. Further, the effect of homocysteine on BNIP3
      gene expression was studied in human aortic endothelial cells in vitro. CAD cases
      exhibited upregulation of BNIP3, downregulation of EC-SOD and GSTP1.
      Hypomethylation of BNIP3 and hypermethylation of EC-SOD were observed in CAD
      cases. The expression of BNIP3 was positively correlated with homocysteine, MDA,
      protein carbonyls, and methylene tetrahydrofolate reductase C677T, while showing
      inverse association with cytosolic serine hydroxymethyl transferase C1420T. The
      expressions of EC-SOD and GSTP1 showed positive association with thymidylate
      synthase (TYMS) 2R3R, while inverse association with MDA, protein carbonyls, and
      methionine synthase reductase (MTRR) A66G. In vitro analysis showed homocysteine
      dependent upregulation of BNIP3. The results of this study suggest that the
      aberrations in one-carbon metabolism appear to induce altered gene expression of
      EC-SOD, GSTP1, and BNIP3, and thus contribute to the increased oxidative stress
      and increased susceptibility to CAD.

PMID- 23160802
TI  - Molecular characterization and identification of the E2/P4 response element in
      the porcine HOXA10 gene.
AB  - Homeobox A10 (HOXA10), a well-known transcriptional factor that can be regulated
      by estrogen (E(2)) and progesterone (P(4)), is necessary not only for endometrial
      differentiation but also for establishing the conditions required for
      implantation. However, little research has focused on the regulation of the
      porcine HOXA10 gene. In this study, we aimed to (1) characterize the genetic
      structure of the porcine HOXA10 gene, (2) analyze the tissue expression pattern
      and differential expression levels in the endometrium of HOXA10 in different
      developmental stages of Meishan and commercial Yorkshire pigs, and (3) identify
      the E2/P4 response element in the promoter region of the porcine HOXA10 gene and
      verify that it induces HOXA10 in human endometrial adenocarcinoma (Ishikawa)
      cells. The results indicated that the cDNA of porcine HOXA10 was 2,628 bp in
      length with an open reading frame (ORF) of 1,236 bp encoding a peptide of 411
      amino acid residues, which showed 90 and 95 % sequence similarity to that of
      human and mouse homologs, respectively. Semiquantitative RT-PCR confirmed that
      the porcine HOXA10 gene is highly expressed in the endometrium, bladder and
      kidney. Real-time PCR showed that the expression of HOXA10 was significantly
      higher on day 15 of gestation (gd 15) in comparison to gd 26 (P < 0.01), gd 50 (P
      < 0.01) and day 15 of the estrous cycle (ed 15) in the endometrium of Meishan
      pigs. In contrast, the highest expression in the endometrium of Yorkshire pigs
      was on gd 50. Moreover, the abundance of HOXA10 mRNA was the highest on gd 15 in
      Meishan pigs than in any other stage tested in the two breeds. Deletion analysis
      and reporter expression assays identified a promoter region (-1044 bp to +18 bp)
      which is responsible for E(2)- and P(4)-induced HOXA10 transcription. Moreover,
      this promoter region enhanced the E2/P4-induced HOXA10 expression in Ishikawa
      cells. In conclusion, we identified an E(2)/P(4) response element of the porcine
      HOXA10 gene for the first time. The data from the present study contribute to the
      mechanism by which the porcine HOXA10 gene regulates embryo implantation and
      prolificacy traits.

PMID- 23160803
TI  - Reconstruction of the rotation center of the hip after oblong cups in revision
      total hip arthroplasty.
AB  - BACKGROUND: The preoperative bone defect and the reconstruction of the center of
      rotation of the hip are critical in acetabular revision surgery. Uncemented
      oblong cups are employed in order to manage these issues. We analyzed the
      clinical results and rates of revision of two different uncemented oblong cups,
      the reconstruction of the center of rotation of the hip, as well as the rate of
      radiological loosening and possible risk factors. MATERIALS AND METHODS: Forty
      five patients (46 hips) underwent acetabular revision surgery using two different
      uncemented oblong cups. We assessed the clinical results and the survival rate
      for revision and aseptic loosening. Intraoperative bone loss was classified
      according to Paprosky, and acetabular reconstruction was assessed according to
      Ranawat. The mean follow-up was 7.2 years (range 4-11 years). RESULTS: There were
      four re-revisions (three due to aseptic loosening); the survival rate for re
      revision due to aseptic loosening was 60.1 % at seven years. The mean distance
      between the center of the femoral head prosthesis and the approximate center of
      the femoral head improved from 21.5 to 10.2 mm. Thirteen cups showed radiological
      loosening; the survival rate for radiological loosening at seven years was 40.54
      %. A smaller postoperative horizontal distance was correlated with cup loosening.
      CONCLUSIONS: Although optimal acetabular reconstruction can be achieved by using
      oblong uncemented cups in revision hip surgery, the clinical and radiological
      results are not encouraging. Excessive medialization of the cup may increase the
      rate of loosening.

PMID- 23160804
TI  - Development of rapid and highly sensitive HSPA1A promoter-driven luciferase
      reporter system for assessing oxidative stress associated with low-dose
      photodynamic therapy.
AB  - Photodynamic therapy (PDT) is a regulatory-approved modality for treating a
      variety of malignant tumors. It induces tumor tissue damage via photosensitizer
      mediated oxidative cytotoxicity. The heat shock protein 70 (HSP70-1) is a stress
      protein encoded by the HSPA1A gene and is significantly induced by oxidative
      stress associated with PDT. The aim of this study was to identify the functional
      region of the HSPA1A promoter that responds to PDT-induced oxidative stress and
      uses the stress responsiveness of HSPA1A expression to establish a rapid and cost
      effective photocytotoxic assessment bioassay to evaluate the photodynamic
      potential of photosensitizers. By constructing luciferase vectors with a variety
      of hspa1a promoter fractions and examining their relative luciferase activity, we
      demonstrated that the DNA sequence from -218 to +87 of the HSPA1A gene could be
      used as a functional promoter to detect the PDT-induced oxidative stress. The
      maximal relative luciferase activity level of HSPA1A (HSP70-1) induced by
      hypericin-PDT was nearly nine times that of the control. Our results suggest that
      the novel reporter gene assay using a functional region of the HSP70A1A promoter
      has significant advantages for the detection of photoactivity in terms of both
      speed and sensitivity, when compared with a cell viability test based on ATP
      quantification and ROS levels. Furthermore, phthalocyanine zinc and methylene
      blue both induced significantly elevated levels of relative luciferase activity
      in a dose-dependent manner.

PMID- 23160805
TI  - A modified UPR stress sensing system reveals a novel tissue distribution of
      IRE1/XBP1 activity during normal Drosophila development.
AB  - Eukaryotic cells respond to stress caused by the accumulation of
      unfolded/misfolded proteins in the endoplasmic reticulum by activating the
      intracellular signaling pathways referred to as the unfolded protein response
      (UPR). In metazoans, UPR consists of three parallel branches, each characterized
      by its stress sensor protein, IRE1, ATF6, and PERK, respectively. In Drosophila,
      IRE1/XBP1 pathway is considered to function as a major branch of UPR; however,
      its physiological roles during the normal development and homeostasis remain
      poorly understood. To visualize IRE1/XBP1 activity in fly tissues under normal
      physiological conditions, we modified previously reported XBP1 stress sensing
      systems (Souid et al., Dev Genes Evol 217: 159-167, 2007; Ryoo et al., EMBO J 26:
      242-252, 2007), based on the recent reports regarding the unconventional splicing
      of XBP1/HAC1 mRNA (Aragon et al., Nature 457: 736-740, 2009; Yanagitani et al.,
      Mol Cell 34: 191-200, 2009; Science 331: 586-589, 2011). The improved XBP1 stress
      sensing system allowed us to detect new IRE1/XBP1 activities in the brain, gut,
      Malpighian tubules, and trachea of third instar larvae and in the adult male
      reproductive organ. Specifically, in the larval brain, IRE1/XBP1 activity was
      detected exclusively in glia, although previous reports have largely focused on
      IRE1/XBP1 activity in neurons. Unexpected glial IRE1/XBP1 activity may provide us
      with novel insights into the brain homeostasis regulated by the UPR.

PMID- 23160806
TI  - Functional relevance of J-protein family of rice (Oryza sativa).
AB  - Protein folding and disaggregation are crucial processes for survival of cells
      under unfavorable conditions. A network of molecular chaperones supports these
      processes. Collaborative action of Hsp70 and Hsp100 proteins is an important
      component of this network. J-proteins/DnaJ members as co-chaperones assist Hsp70.
      As against 22 DnaJ sequences noted in yeast, rice genome contains 104 J-genes.
      Rice J-genes were systematically classified into type A (12 sequences), type B (9
      sequences), and type C (83 sequences) classes and a scheme of nomenclature of
      these proteins is proposed. Transcript expression profiles revealed that J
      proteins are possibly involved in basal cellular activities, developmental
      programs, and in stress. Ydj1 is the most abundant J-protein in yeast. Ydj1
      deleted yeast cells are nonviable at 37  degrees C. Two rice ortholog proteins of
      yeast Ydj1 protein namely OsDjA4 and OsDjA5 successfully rescued the growth
      defect in mutant yeast. As Hsp70 and J-proteins work in conjunction, it emerges
      that rice J-proteins can partner with yeast Hsp70 proteins in functioning. It is
      thus shown that J-protein machine is highly conserved.

PMID- 23160807
TI  - A cortical cystic epileptogenic lesion: tanycytic ependymoma.

PMID- 23160808
TI  - Autonomic dysfunction in multiple sclerosis presenting with postural orthostatic
      tachycardia.

PMID- 23160809
TI  - Vitamin D supplementation in multiple sclerosis patients in 2012: hype or reality
      as an adjunctive therapy?

PMID- 23160810
TI  - Unilateral cranial autonomic symptoms in patients with migraine.
AB  - The aim of this study is to investigate the frequency of unilateral cranial
      autonomic symptoms during migraine attacks, and to compare the clinical
      characteristics of migraine patients with and without unilateral cranial
      autonomic symptoms. One hundred and eighty-six consecutive patients with episodic
      migraine attacks were prospectively included. Cranial autonomic symptoms of the
      patients occurred during headache, frequency, duration, severity and character of
      headache, disease duration, presence of aura, laterality of headache,
      accompanying symptoms, relation of migraine attacks with menstruation, lesions
      detected on magnetic resonance images, and family history of migraine were
      recorded. The patients with and without unilateral cranial autonomic symptoms
      during headache were compared in terms of above-mentioned parameters. Seventy
      seven (41.4 %) patients were observed to develop unilateral cranial autonomic
      symptoms during migraine attack. Disease duration was longer in the patients with
      unilateral cranial autonomic symptoms than in those without (p = 0.045). Headache
      was unilateral in 83.1 % of the patients with unilateral cranial autonomic
      symptoms (p = 0.001). Pure menstrual or menstrually related migraine attacks were
      more common in the patients with unilateral cranial autonomic symptoms (p =
      0.043) and is thought that menstruation-related hormonal factors might have a
      triggering role on the trigeminal-autonomic reflex pathway. The longer disease
      duration in patients with unilateral cranial autonomic symptoms might be
      associated with the activation of pathophysiological mechanisms that cause
      cranial autonomic symptoms in time. Frequent unilateral pain in migraine patients
      with unilateral cranial autonomic symptoms is likely to indicate that the
      development of autonomic symptoms may share common mechanisms with the
      pathogenesis of trigeminal autonomic cephalalgias.

PMID- 23160811
TI  - The behavioral and neural effect of emotional primes on intertemporal decisions.
AB  - Research on intertemporal behavior has emphasized trait-like variance. However,
      recent studies have begun to explore situational factors that affect
      intertemporal preference. In this study, we examined the associations between
      emotional primes and both behavior and brain function during intertemporal
      decision making. Twenty-two participants completed a dual task in which they were
      required to make intertemporal choices while holding an expressive face in
      memory. From trial-to-trial, the facial expression varied between three
      alternatives: (i) fearful, (ii) happy and (iii) neutral. Brain activity was
      recorded using functional magnetic resonance imaging for 16 participants.
      Behavioral data indicated that fearful (relative to happy) faces were associated
      with greater preference for larger but later rewards. During observation of
      fearful faces, greater signal change was observed in the right dorsolateral
      prefrontal cortex. During subsequent decision making, the fear prime was
      associated with greater signal increase in structures including the posterior
      sector of the anterior cingulate cortex. Individual differences in this activity
      correlated with the magnitude of the priming effect on behavior. These findings
      suggest that incidental emotions affect intertemporal choice. Increased
      farsightedness after the fear prime may be explained by an 'inhibition spillover'
      effect. 

PMID- 23160812
TI  - Roman Catholic beliefs produce characteristic neural responses to moral dilemmas.
AB  - This study provides exploratory evidence about how behavioral and neural
      responses to standard moral dilemmas are influenced by religious belief. Eleven
      Catholics and 13 Atheists (all female) judged 48 moral dilemmas. Differential
      neural activity between the two groups was found in precuneus and in prefrontal,
      frontal and temporal regions. Furthermore, a double dissociation showed that
      Catholics recruited different areas for deontological (precuneus; temporoparietal
      junction) and utilitarian moral judgments [dorsolateral prefrontal cortex
      (DLPFC); temporal poles], whereas Atheists did not (superior parietal gyrus for
      both types of judgment). Finally, we tested how both groups responded to personal
      and impersonal moral dilemmas: Catholics showed enhanced activity in DLPFC and
      posterior cingulate cortex during utilitarian moral judgments to impersonal moral
      dilemmas and enhanced responses in anterior cingulate cortex and superior
      temporal sulcus during deontological moral judgments to personal moral dilemmas.
      Our results indicate that moral judgment can be influenced by an acquired set of
      norms and conventions transmitted through religious indoctrination and practice.
      Catholic individuals may hold enhanced awareness of the incommensurability
      between two unequivocal doctrines of the Catholic belief set, triggered
      explicitly in a moral dilemma: help and care in all circumstances-but thou shalt
      not kill. 

PMID- 23160813
TI  - Power corrupts co-operation: cognitive and motivational effects in a double EEG
      paradigm.
AB  - This study investigated the effect of interpersonal power on co-operative
      performance. We used a paired electro-encephalogram paradigm: pairs of
      participants performed an attention task, followed by feedback indicating
      monetary loss or gain on every trial. Participants were randomly allocated to the
      power-holder, subordinate or neutral group by creating different levels of
      control over how a joint monetary reward would be allocated. We found that power
      was associated with reduced behavioural accuracy. Event-related potential
      analysis showed that power-holders devoted less motivational resources to their
      targets than did subordinates or neutrals, but did not differ at the level of
      early conflict detection. Their feedback potential results showed a greater
      expectation of rewards but reduced subjective magnitude attributed to losses.
      Subordinates, on the other hand, were asymmetrically sensitive to power-holders'
      targets. They expected fewer rewards, but attributed greater significance to
      losses. Our study shows that power corrupts balanced co-operation with
      subordinates. 

PMID- 23160814
TI  - Interdependent selves show face-induced facilitation of error processing:
      cultural neuroscience of self-threat.
AB  - The fundamentally social nature of humans is revealed in their exquisitely high
      sensitivity to potentially negative evaluations held by others. At present,
      however, little is known about neurocortical correlates of the response to such
      social-evaluative threat. Here, we addressed this issue by showing that mere
      exposure to an image of a watching face is sufficient to automatically evoke a
      social-evaluative threat for those who are relatively high in interdependent self
      construal. Both European American and Asian participants performed a flanker task
      while primed with a face (vs control) image. The relative increase of the error
      related negativity (ERN) in the face (vs control) priming condition became more
      pronounced as a function of interdependent (vs independent) self-construal.
      Relative to European Americans, Asians were more interdependent and, as
      predicted, they showed a reliably stronger ERN in the face (vs control) priming
      condition. Our findings suggest that the ERN can serve as a robust empirical
      marker of self-threat that is closely modulated by socio-cultural variables. 

PMID- 23160815
TI  - Temporal dynamics of emotional responding: amygdala recovery predicts emotional
      traits.
AB  - An individual's affective style is influenced by many things, including the
      manner in which an individual responds to an emotional challenge. Emotional
      response is composed of a number of factors, two of which are the initial
      reactivity to an emotional stimulus and the subsequent recovery once the stimulus
      terminates or ceases to be relevant. However, most neuroimaging studies examining
      emotional processing in humans focus on the magnitude of initial reactivity to a
      stimulus rather than the prolonged response. In this study, we use functional
      magnetic resonance imaging to study the time course of amygdala activity in
      healthy adults in response to presentation of negative images. We split the
      amygdala time course into an initial reactivity period and a recovery period
      beginning after the offset of the stimulus. We find that initial reactivity in
      the amygdala does not predict trait measures of affective style. Conversely,
      amygdala recovery shows predictive power such that slower amygdala recovery from
      negative images predicts greater trait neuroticism, in addition to lower levels
      of likability of a set of social stimuli (neutral faces). These data underscore
      the importance of taking into account temporal dynamics when studying affective
      processing using neuroimaging. 

PMID- 23160816
TI  - Orbitofrontal sulcogyral patterns are related to temperamental risk for
      psychopathology.
AB  - There are marked individual differences in the pattern of cortical (sulcogyral)
      folding in the orbitofrontal cortex (OFC), and there is a growing literature
      suggesting that these individual differences are associated with risk for
      psychotic disorders. To date, however, no study has investigated whether OFC
      folding patterns are associated with broader risk factors relevant to a range of
      psychopathology. This study helps address this knowledge gap by examining whether
      OFC sulcogyral folding patterns are associated with putative risk factors,
      specifically affective temperament and psychiatric symptoms, in a large community
      sample (N = 152) of adolescents. Results showed that the most common pattern of
      folding ('Type I', marked by discontinuity of the medial orbital sulcus and
      continuity of the lateral orbital sulcus) was associated with low levels of
      Surgency, high levels of Negative Affectivity (in girls) and higher depressive
      symptoms. This pattern was also associated with reduced thickness of OFC gray
      matter. Overall, the findings, combined with previous work, suggest some
      specificity of neurodevelopmental risk for different types of psychopathology.
      Thus, these results have the potential to inform the early identification of at
      risk individuals. 

PMID- 23160818
TI  - Metabolic transformation of antitumor acridinone C-1305 but not C-1311 via
      selective cellular expression of UGT1A10 increases cytotoxic response:
      implications for clinical use.
AB  - The acridinone derivates 5-dimethylaminopropylamino-8-hydroxytriazoloacridinone
      (C-1305) and 5-diethylaminoethylamino-8-hydroxyimidazoacridinone (C-1311) are
      promising antitumor agents with high activity against several experimental
      cellular and tumor models and are under evaluation in preclinical and early phase
      clinical trials. Recent evidence from our laboratories has indicated that both
      compounds were conjugated by several uridine diphosphate-glucuronyltransferase
      (UGT) isoforms, the most active being extrahepatic UGT1A10. The present studies
      were designed to test the ability and selectivity of UGT1A10 in the
      glucuronidation of acridinone antitumor agents in a cellular context. We show
      that in KB-3 cells, a HeLa subline lacking expression of any UGT isoforms, both C
      1305 and C-1311 undergo metabolic transformation to the glucuronidated forms on
      overexpression of UGT1A10. Furthermore, UGT1A10 overexpression significantly
      increased the cytotoxicity of C-1305, but not C-1311, suggesting that the
      glucuronide was more potent than the C-1305 parent compound. These responses were
      selective for UGT1A10 because documented overexpression of UGT2B4 failed to
      produce glucuronide products and failed to alter the cytotoxicity for both
      compounds. These findings contribute to our understanding of the mechanisms of
      action of these agents and are of particular significance because data for C-1305
      contradict the dogma that glucuronidation typically plays a role in
      detoxification or deactivation. In summary, these studies suggest that
      extrahepatic UGT1A10 plays an important role in the metabolism and the
      bioactivation of C-1305 and constitutes the basis for further mechanistic studies
      on the mode of action of this drug, as well as translational studies on the role
      of this enzyme in regulation of C-1305 toxicity in cancer.

PMID- 23160817
TI  - Subclinical delusional thinking predicts lateral temporal cortex responses during
      social reflection.
AB  - Neuroimaging studies have demonstrated associations between delusions in
      psychotic disorders and abnormalities of brain areas involved in social
      cognition, including medial prefrontal cortex (MPFC), posterior cingulate cortex,
      and lateral temporal cortex (LTC). General population studies have linked
      subclinical delusional thinking to impaired social cognition, raising the
      question of whether a specific pattern of brain activity during social perception
      is associated with delusional beliefs. Here, we tested the hypothesis that
      subclinical delusional thinking is associated with changes in neural function,
      while subjects made judgments about themselves or others ['social reflection'
      (SR)]. Neural responses during SR and non-social tasks, as well as resting-state
      activity, were measured using functional magnetic resonance imaging in 22 healthy
      subjects. Delusional thinking was measured using the Peters et al. Delusions
      Inventory. Delusional thinking was negatively correlated with responses of the
      left LTC during SR (r = -0.61, P = 0.02, Bonferroni corrected), and connectivity
      between the left LTC and left ventral MPFC, and was positively correlated with
      connectivity between the left LTC and the right middle frontal and inferior
      temporal cortices. Thus, delusional thinking in the general population may be
      associated with reduced activity and aberrant functional connectivity of cortical
      areas involved in SR. 

PMID- 23160819
TI  - Dietary regulation of mouse intestinal P450 expression and drug metabolism.
AB  - The study was originally designed to test the hypothesis that the compensatory
      increase in intestinal P450 (cytochrome P450) expression in the intestinal
      epithelium-specific P450 reductase (CPR) knockout (IE-Cpr-null) mice was
      attributable to decreased metabolism of putative P450 inducers present in the
      diet. Thus, we determined the impact of a dietary change from regular rodent chow
      to a synthetic diet devoid of phytochemicals on the expression of P450 enzymes in
      the small intestine (SI) and liver of wild-type (WT) and IE-Cpr-null mice. The
      dietary change diminished expression of CYP1A, 2B, 2C, and 3A in SI and CYP2B,
      2C, and 3A in liver of both WT and IE-Cpr-null mice. However, the compensatory
      increase in SI P450 expression still occurred in IE-Cpr-null, compared with WT,
      mice, on the synthetic diet. The diet change-induced decrease in P450 expression
      was accompanied by decreases in microsomal midazolam-hydroxylase activity in
      vitro and first-pass clearance of midazolam in vivo in WT mice. Further studies
      showed that the dietary change, but not Cpr deletion, caused large decreases in
      bile acid (BA) levels in plasma, liver, SI, and intestinal content and that
      treatment of WT mice on the synthetic diet with GW4064, a farnesoid-X-receptor
      agonist, restored the levels of CYP3A expression in both liver and SI to those
      seen in mice fed with regular chow. Taken together, these results highlight the
      vital role of diet in maintaining adequate expression of major drug-metabolizing
      P450s and their associated drug-metabolizing activities in the digestive tract
      and suggest potential involvement of BA signaling in the regulatory mechanisms.

PMID- 23160820
TI  - RBCK1, an E3 ubiquitin ligase, interacts with and ubiquinates the human pregnane
      X receptor.
AB  - The pregnane X receptor (PXR, NR1I2) plays a pivotal role in the disposition and
      detoxification of numerous foreign and endogenous chemicals by increasing
      transcription of numerous target genes, including phase I and II drug
      metabolizing enzymes and transporters. In the present study, yeast two-hybrid
      screening identified an E3 ubiquitin ligase, RBCK1 (Ring-B-box-coiled-coil
      protein interacting with protein kinase C-1), as a human pregnane X receptor
      (hPXR)-interacting protein. Coimmunoprecipitation studies confirmed the
      interaction between RBCK1 and hPXR when both were ectopically expressed in AD-293
      cells. Domain mapping studies showed that the interaction between RBCK1 and hPXR
      involves all RBCK1 domains. We further demonstrate that RBCK1 ubiquitinates hPXR,
      and this may target hPXR for degradation by the ubiquitin-proteasome pathway.
      Simultaneous ectopic overexpression of RBCK1 and PXR decreased PXR levels in AD
      293 cells, and this decrease was inhibited by the proteasomal inhibitor MG-132
      (carbobenzoxy-Leu-Leu-leucinal). Furthermore, overexpression of RBCK1 decreased
      endogenous levels of PXR in HepG2 cells. Of importance, ectopic overexpression
      and silencing of endogenous RBCK1 in primary human hepatocytes resulted in a
      decrease and increase, respectively, in endogenous PXR protein levels and in the
      induction of PXR target genes by rifampicin. These results suggest that RBCK1 is
      important for the ubiquitination of PXR and may play a role in its proteasomal
      degradation.

PMID- 23160822
TI  - Transscleral diode laser cyclophotocoagulation for refractory glaucoma secondary
      to juvenile idiopathic arthritis: a short term follow-up.
AB  - To evaluate the success rates of transscleral diode cyclophotocoagulation (TD
      CPC) for refractory secondary glaucoma in a paediatric patient with juvenile
      idiopathic arthritis. Report of a case of a 6-year-old boy suffering from severe
      uveitis, and secondary open angle glaucoma. The patient had undergone bilateral
      cataract surgery, two prior trabeculectomies in the left and one in the right
      eye. He was under systemic immunomodulation with methotrexate and cyclosporine.
      He presented with medically uncontrolled glaucoma, with an intraocular pressure
      (IOP) of 36 and 34 mmHg in the right and left eye, respectively, under maximal
      medical antiglaucoma therapy. TD-CPC was performed under general anesthesia,
      including a total of 20 spots in the right and 34 in the left eye (2,000 mW, 2
      s/spot) applied in one session. Visual acuity remained stable in the right eye
      and deteriorated in the left eye from 0.1 to no light perception. Postoperative
      hypotony was present 1 month post op and IOP was 14 mmHg in the left and 17 mmHg
      in the right eye, respectively, in the 6-month follow-up with a topical beta
      blocker. The anterior chamber was quiet in both eyes. TD-CPC was effective in the
      short term as IOP lowering therapy in a pediatric patient with refractory uveitic
      glaucoma. 

PMID- 23160821
TI  - Cytochrome P450 regulation by alpha-tocopherol in Pxr-null and PXR-humanized
      mice.
AB  - The pregnane X receptor (PXR) has been postulated to play a role in the
      metabolism of alpha-tocopherol owing to the up-regulation of hepatic cytochrome
      P450 (P450) 3A in human cell lines and murine models after alpha-tocopherol
      treatment. However, in vivo studies confirming the role of PXR in alpha
      tocopherol metabolism in humans presents significant difficulties and has not
      been performed. PXR-humanized (hPXR), wild-type, and Pxr-null mouse models were
      used to determine whether alpha-tocopherol metabolism is influenced by species
      specific differences in PXR function in vivo. No significant difference in the
      concentration of the major alpha-tocopherol metabolites was observed among the
      hPXR, wild-type, and Pxr-null mice through mass spectrometry-based metabolomics.
      Gene expression analysis revealed significantly increased expression of Cyp3a11
      as well as several other P450s only in wild-type mice, suggesting species
      specificity for alpha-tocopherol activation of PXR. Luciferase reporter assay
      confirmed activation of mouse PXR by alpha-tocopherol. Analysis of the Cyp2c
      family of genes revealed increased expression of Cyp2c29, Cyp2c37, and Cyp2c55 in
      wild-type, hPXR, and Pxr-null mice, which suggests PXR-independent induction of
      Cyp2c gene expression. This study revealed that alpha-tocopherol is a partial
      agonist of PXR and that PXR is necessary for Cyp3a induction by alpha-tocopherol.
      The implications of a novel role for alpha-tocopherol in Cyp2c gene regulation
      are also discussed.

PMID- 23160823
TI  - Visual function after pars plana vitrectomy in macular edema with branch retinal
      vein occlusion.
AB  - The objective of this study is to evaluate functional and morphological changes
      of the macula after pars plana vitrectomy (PPV) for macular edema with branch
      retinal vein occlusion (BRVO). Eighteen patients with BRVO (mean age: 71.3 +/-
      5.9 years; six women and 12 men) received PPV. Macular function was documented by
      microperimetry and best-corrected visual acuity (BCVA) was determined. Retinal
      thickness and retinal volume were measured by optical coherence tomography (OCT),
      and mean retinal sensitivity was calculated for each of nine macular subfields.
      Ischemia and serous retinal detachment (SRD) were evaluated by fluorescein
      angiography and OCT, respectively. Mean BCVA was significantly improved at 3 and
      6 months after PPV. Mean retinal sensitivity, retinal thickness, and retinal
      volume were significantly improved after 3 and 6 months in five, eight, and eight
      subfields, respectively. Improvement of visual acuity and the percent change in
      retinal thickness or retinal volume were not correlated in any of the nine
      subfields, while improvement of retinal sensitivity was correlated with the
      percent change in both retinal thickness and retinal volume in the temporal outer
      subfield. There were significant differences with respect to the percent changes
      in retinal thickness and volume in the temporal outer field between the non
      ischemic and ischemic groups, as well as between the patients with and without
      SRD. There was also a significant difference between the non-ischemic and
      ischemic groups with respect to the improvement of retinal sensitivity in three
      out of nine fields. These findings suggest that PPV can improve both functional
      and morphological changes due to macular edema in BRVO patients, and that
      morphological improvement in the temporal outer subfield after PPV might
      influence the functional prognosis of these patients.

PMID- 23160824
TI  - Management of recurrent intra corneal epithelial cyst with ethanol irrigation and
      vacuum-assisted cyst wall excision.
AB  - The clinical and pathological features and management of a patient with recurrent
      intracorneal epithelial cyst are reported. A child presented with a large
      intracorneal cyst and underwent drainage with 96 % ethanol irrigation.
      Histopathology confirmed the epithelial nature of the cyst. The cyst recurred,
      however, and subsequently a repeat ethanol irrigation with removal of the cyst
      wall was done. The cyst wall was vacuumed to ensure complete removal of
      epithelial cells. There was no recurrence, with good visual and cosmetic
      recovery. Intracorneal epithelial cysts can be successfully managed with
      drainage, 96 % ethanol irrigation, and vacuum-assisted cyst wall excision. 

PMID- 23160825
TI  - Grading severity in retinitis pigmentosa using clinical assessment, visual
      acuity, perimetry and optical coherence tomography.
AB  - To develop a grading system for retinitis pigmentosa (RP), providing clinicians
      with a simple, objective measure of disease severity. An observational case
      series of 14 patients with RP. Disease severity was assessed using four criteria;
      clinical appearance, visual acuity (best corrected LogMAR, BCVA), perimetry (mean
      deviation, MD) and Fourier-domain optical coherence tomography (outer retinal
      thickness, ORT at the fovea). Each criterion was scored on a severity scale from
      0 (mild disease) to 4 (severe disease), giving an overall score out of 16. The
      mean BCVA was 0.37 LogMAR (range 0.02 to PL), mean MD was -25.35 dB (range -7.48
      to -34.38 dB), mean retinal thickness at the fovea was 189.4 MUm (range 96.5
      264.5 MUm) and mean ORT at the fovea was 140.6 MUm (range 63.4-193.4 MUm). The
      clinical appearance correlated well with each of the quantitative measures of
      disease severity; BCVA (0.62, p = 0.022), MD (-0.903, p < 0.0001) and ORT (
      0.698, p = 0.005). Applying the grading system to our patients, the severity
      scores were evenly spread between grades 1 and 14. We present a simple, objective
      grading system for RP offering a potential tool for grading disease severity with
      applications such as assessing progression, comparing patient populations and
      measuring outcomes in clinical trials.

PMID- 23160826
TI  - Pteridine-, thymidine-, choline- and imidazole-derived alkaloids from the
      Australian ascidian, Leptoclinides durus.
AB  - Four new acylated pteridine alkaloids, duramidines A-D, two new acylated
      thymidine alkaloids, leptoclinidines A and B, two new 1-acylglyceryl-3-(O
      carboxyhydroxymethylcholine) alkaloids, durabetaines A and B, three new 1,3
      dimethyl-5-methylsulfanylimidazole alkaloids, leptoclinidamines D-F, and the
      known alkaloids leptoclinidamines B and C and 6-bromo-1H-indolo-3-yl-oxoacetic
      acid methyl ester were isolated from the Australian ascidian Leptoclinides durus.
      The duramidines are the first pteridine alkaloids, possessing a three carbon side
      chain esterified at C-1' with a 4-hydroxy-2'-methoxycinnamic acid, and are either
      hydroxylated or sulfated at C-2'. The leptoclinidines are the first 3'-indole-3
      carboxylic acid ester derivatives of thymidine to be reported in the literature.
      The durabetaines are the first glyceryl-3-(O-carboxyhydroxymethylcholine)
      alkaloids to be reported from an animal source and are also the only known
      derivatives from this class to be acylated with aromatic carboxylic acids. MS and
      NMR data analysis established the structures of the new compounds. All compounds
      were shown to be inactive when tested for cytotoxic activity against prostate
      (LNCaP) and breast (MDA-MB-231) cancer cell lines and antimicrobial activity
      against Pseudomonas aeruginosa and Staphylococcus aureus.

PMID- 23160827
TI  - A simulation study on the relation between muscle motor unit numbers and the non
      Gaussianity/non-linearity levels of surface electromyography.
AB  - Recent research has demonstrated that surface electromyography (sEMG) signals
      have non-Gaussianity and non-linearity properties. It is known that more muscle
      motor units are recruited and firing rates (FRs) increase as exertion increases.
      A hypothesis was proposed that the Gaussianity test (S (g)) and linearity test (S
      (l)) levels of sEMG signals are associated with the number of active motor units
      (nMUs) and the FR. The hypothesis has only been preliminarily discussed in
      experimental studies. We used a simulation sEMG model involving spatial (active
      MUs) and temporal (three FRs) information to test the hypothesis. Higher-order
      statistics (HOS) from the bi-frequency domain were used to perform S (g) and S
      (l). Multivariate covariance analysis and a correlation test were employed to
      determine the nMUs-S (g) relationship and the nMUs-S (l) relationship. Results
      showed that nMUs, the FR, and the interaction of nMUs and the FR all influenced
      the S (g) and S (l) values. The nMUs negatively correlated to both the S (g) and
      S (l) values. That is, at the three FRs, sEMG signals tended to a more Gaussian
      and linear distribution as exertion and nMUs increased. The study limited
      experiment factors to the sEMG non-Gaussianity and non-linearity levels. The
      study quantitatively described nMUs and the FR of muscle that are not directly
      available from experiments. Our finding has guiding significance for muscle
      capability assessment and prosthetic control.

PMID- 23160828
TI  - Atomic force microscopy imaging and mechanical properties measurement of red
      blood cells and aggressive cancer cells.
AB  - Mechanical properties play an important role in regulating cellular activities
      and are critical for unlocking the mysteries of life. Atomic force microscopy
      (AFM) enables researchers to measure mechanical properties of single living cells
      under physiological conditions. Here, AFM was used to investigate the topography
      and mechanical properties of red blood cells (RBCs) and three types of aggressive
      cancer cells (Burkitt's lymphoma Raji, cutaneous lymphoma Hut, and chronic
      myeloid leukemia K562). The surface topography of the RBCs and the three cancer
      cells was mapped with a conventional AFM probe, while mechanical properties were
      investigated with a micro-sphere glued onto a tip-less cantilever. The diameters
      of RBCs are significantly smaller than those of the cancer cells, and mechanical
      measurements indicated that Young's modulus of RBCs is smaller than those of the
      cancer cells. Aggressive cancer cells have a lower Young's modulus than that of
      indolent cancer cells, which may improve our understanding of metastasis.

PMID- 23160829
TI  - Protein differential expression in the elongating cotton (Gossypium hirsutum L.)
      fiber under nitrogen stress.
AB  - Nitrogen (N) is an essential macronutrient and an important factor limiting
      agricultural productivity. N deficient or excess conditions often occur during
      the cotton growth season and incorrect N application may affect cotton fiber
      yield and quality. Here, the influence of N stress on the cotton fiber proteome
      was investigated by two-dimensional gel electrophoresis and mass spectrometry.
      The results indicated that N application rate affects nitrogen accumulation in
      fiber cells and fiber length. The proteins differentially expressed during N
      stress were mainly related to plant carbohydrate metabolism, cell wall component
      synthesis and transportation, protein/amino acid metabolism, antioxidation and
      hormone metabolism. The most abundant proteins were C metabolism-related. Ten
      days post anthesis is a critical time for fiber cells to perceive environmental
      stress and most proteins were suppressed in both N deficient and N excess
      conditions at this sampling stage. However, several N metabolism proteins were
      increased to enhance N stress tolerance. Excess N may suppress
      carbohydrate/energy metabolism in early fiber development much like N deficiency.
      These results have identified some interesting proteins that can be further
      analyzed to elucidate the molecular mechanisms of N tolerance.

PMID- 23160830
TI  - Discussion on research methods of bacterial resistant mutation mechanisms under
      selective culture--uncertainty analysis of data from the Luria-Delbruck
      fluctuation experiment.
AB  - Whether bacterial drug-resistance is drug-induced or results from rapid
      propagation of random spontaneous mutations in the flora prior to exposure,
      remains a long-term key issue concerned and debated in both genetics and
      medicinal fields. In a pioneering study, Luria and Delbruck exposed E. coli to T1
      phage, to investigate whether the number of resistant colonies followed the
      Poisson distribution. They deduced that the development of resistant colonies is
      independent of phage presence. Similar results have since been obtained on solid
      medium containing antibacterial agents. Luria and Delbruck's conclusions were
      long considered a gold standard for analyzing drug resistance mutations. More
      recently, the concept of adaptive mutation has triggered controversy over this
      approach. Microbiological observation shows that, following exposure to drugs of
      various concentrations, drug-resistant cells emerge and multiply depending on the
      time course, and show a process function, inconsistent with the definition of
      Poisson distribution (which assumes not only that resistance is independent of
      drug quantity but follows no specific time course). At the same time, since cells
      tend to aggregate after division rather than separating, colonies growing on drug
      plates arise from the multiplication of resistant bacteria cells of various
      initial population sizes. Thus, statistical analysis based on equivalence of
      initial populations will yield erroneous results. In this paper, 310 data from
      the Luria-Delbruck fluctuation experiment were reanalyzed from this perspective.
      In most cases, a high-end abnormal value, resulting from the non-synchronous
      variation of the two above-mentioned time variables, was observed. Therefore, the
      mean value cannot be regarded as an unbiased expectation estimate. The ratio
      between mean value and variance was similarly incomparable, because two different
      sampling methods were used. In fact, the Luria-Delbruck data appear to follow an
      aggregated, rather than Poisson distribution. In summary, the statistical
      analysis of Luria and Delbruck is insufficient to describe rules of resistant
      mutant development and multiplication. Correction of this historical
      misunderstanding will enable new insight into bacterial resistance mechanisms.

PMID- 23160831
TI  - Recent progress of sensory system research in China.

PMID- 23160832
TI  - Neuroglobin and cytoglobin expression in the human brain.
AB  - Neuroglobin and cytoglobin are new members of the heme-globin family. Both
      globins are primarily expressed in neurons of the brain and retina. Neuroglobin
      and cytoglobin have been suggested as novel therapeutic targets in various
      neurodegenerative diseases based on their oxygen binding and cell protecting
      properties. However, findings in Neuroglobin-deficient mice question the
      endogenous neuroprotective properties. The expression pattern of neuroglobin and
      cytoglobin in the rodent brain is also in contradiction to a major role of
      neuronal protection. In a recent study, neuroglobin was ubiquitously expressed
      and up-regulated following stroke in the human brain. The present study aimed at
      confirming our previous observations in rodents using two post-mortem human
      brains. The anatomical localization of neuroglobin and cytoglobin in the human
      brain is much like what has been described for the rodent brain. Neuroglobin is
      highly expressed in the hypothalamus, amygdale and in the pontine tegmental
      nuclei, but not in the hippocampus. Cytoglobin is highly expressed in the
      habenula, hypothalamus, thalamus, hippocampus and the pontine tegmental nuclei.
      We only detected a low expression of neuroglobin and cytoglobin in the cerebral
      cortex, while no expression in the cerebellar cortex was detectable. We provide a
      neuroanatomical indication for a different role of neuroglobin and cytoglobin in
      the human brain.

PMID- 23160833
TI  - Purkinje cell compartmentalization in the cerebellum of the spontaneous mutant
      mouse dreher.
AB  - The cerebellar morphological phenotype of the spontaneous neurological mutant
      mouse dreher (Lmx1a(dr-J)) results from cell fate changes in dorsal midline
      patterning involving the roof plate and rhombic lip. Positional cloning revealed
      that the gene Lmx1a, which encodes a LIM homeodomain protein, is mutated in
      dreher, and is expressed in the developing roof plate and rhombic lip. Loss of
      Lmx1a causes reduction of the roof plate, an important embryonic signaling
      center, and abnormal cell fate specification within the embryonic cerebellar
      rhombic lip. In adult animals, these defects result in variable, medial fusion of
      the cerebellar vermis and posterior cerebellar vermis hypoplasia. It is unknown
      whether deleting Lmx1a results in displacement or loss of specific lobules in the
      vermis. To distinguish between an ectopic and absent vermis, the expression
      patterns of two Purkinje cell-specific compartmentation antigens, zebrin
      II/aldolase C and the small heat shock protein HSP25 were analyzed in dreher
      cerebella. The data reveal that despite the reduction in volume and abnormal
      foliation of the cerebellum, the transverse zones and parasagittal stripe arrays
      characteristic of the normal vermis are present in dreher, but may be highly
      distorted. In dreher mutants with a severe phenotype, zebrin II stripes are
      fragmented and distributed non-symmetrically about the cerebellar midline. We
      conclude that although Purkinje cell agenesis or selective Purkinje cell death
      may contribute to the dreher phenotype, our data suggest that aberrant anlage
      patterning and granule cell development lead to Purkinje cell ectopia, which
      ultimately causes abnormal cerebellar architecture in dreher.

PMID- 23160835
TI  - Localizing coordinates of cerebral ischemic tissue without the need of staining
      in a rat model of focal cerebral infarct.
AB  - Biochemical and metabolic analysis of ischemic cerebral tissue is central in
      stroke investigation and is usually performed in animal stroke models, such as
      the permanent occlusion of the middle cerebral artery (MCAO) in the rat that we
      have used. To be sure that the sample is from infarct tissue, it is
      differentiated from the surrounding normal tissue by staining, usually with 2,3,5
      triphenyltetrazolium chloride (TTC), but staining can hamper biochemical
      colorimetric analysis. We performed this study to avoid this obstacle. A cerebral
      infarct was provoked in a sample of 10 rats and the brain was cut in coronal
      sections that were stained with TTC so that the unstained, infarct areas could be
      delineated in a template of each section in which areas with infarct in all
      animals were delineated. We calculated infarct coordinates and depth so that the
      infarct tissue can be sampled without staining. For more precision, the ischemic
      cortex can be delimited staining its surface before sectioning and cortical
      tissue into which TTC diffuses can be afterwards discarded, as we had previously
      measured the TTC diffusion depth in rat brains.

PMID- 23160834
TI  - Undernutrition upregulates fumarate hydratase in the rat nucleus accumbens.
AB  - Previous comparative studies of fumarate hydratase (FH) protein density revealed
      that the enzyme was overexpressed in the striatum of rodents that are less
      influenced by rewarding stimuli, from cocaine to food. Therefore, we recently
      proposed FH as a potential striatal biomarker of brain reward deficiency and
      addiction vulnerability. This work has been focused to investigate FH activity in
      the Nucleus Accumbens (NAc) of undernourished rats, taking into account that
      malnutrition has been related to increased responsiveness to food and drug
      reward. To this end, we have studied adult female Wistar rats severely food
      restricted from the 16th day of intrauterine life until adulthood. Animals were
      sacrificed to dissect the NAc and obtain mitochondrial and cytosolic fractions
      after homogenisation and centrifugation. FH activity was measured by conversion
      of malate to fumarate, and protein levels were compared by Western blot analysis
      when fractions showed differences in activity. Undernutrition did not change
      cytosolic FH activity but led to a marked increase of mitochondrial FH activity
      (72 %) and protein content (50 %) in the NAc. This change was in the opposite
      direction that one would predict if it was related to addiction vulnerability of
      some kind, but strongly suggests that mitochondrial FH needs to be at some
      optimal level for normal reward responsiveness.

PMID- 23160836
TI  - Regulation of CXCR4-mediated invasion by DARPP-32 in gastric cancer cells.
AB  - Although Dopamine and cAMP-regulated phosphoprotein, Mr 32000 (DARPP-32) is
      overexpressed in two-thirds of gastric cancers, its impact on molecular functions
      has not been fully characterized. In this study, we examined the role of DARPP-32
      in gastric cancer cell invasion. Using matrigel-coated Boyden chamber invasion
      assay, DARPP-32-overexpressing AGS cells showed a three-fold increase in invasion
      relative to the vector control (P < 0.01). We also tested the transendothelial
      cell invasion as a measure of cell aggressiveness using the impedance-based human
      umbilical vein endothelial cells invasion assay and obtained similar results (P <
      0.001). Western blot analysis indicated that overexpression of DARPP-32 mediated
      an increase in the membrane-type 1 matrix metalloproteinase (MT1-MMP) and CXCR4
      protein levels. Consistent with the role of MT1-MMP in cleaving extracellular
      matrix proteins initiating the activation of soluble MMPs, we detected a robust
      increase in MMP-2 activity in DARPP-32-overexpressing cells. The knockdown of
      endogenous DARPP-32 in the MKN-45 cells reversed these signaling events and
      decreased cell invasive activity. We tested whether the invasive activity
      mediated by DARPP-32 might involve sustained signaling via CXCR4-dependent
      activation of the MT1-MMP/MMP-2 pathway. The small-molecule CXCR4 antagonist
      (AMD3100) and CXCR4-siRNA blocked DARPP-32-induced cell invasion. We further
      examined our hypothesis that DARPP-32 could interact with CXCR4 and stabilize its
      levels following stimulation with its ligand, CXCL12. Using reciprocal
      coimmunoprecipitation and immunofluorescence experiments, we found that DARPP-32
      and CXCR4 coexist in the same protein complex. DARPP-32 prolonged the CXCR4
      protein half-life and reduced ubiquitination of the CXCR4 protein, following
      treatment with its ligand, CXCL12. In conclusion, these findings show a novel
      mechanism by which DARPP-32 promotes cell invasion by regulating CXCR4-mediated
      activation of the MT1-MMP/MMP-2 pathway.

PMID- 23160837
TI  - Targets for antibiotic and healthcare resource stewardship in inpatient community
      acquired pneumonia: a comparison of management practices with National Guideline
      Recommendations.
AB  - PURPOSE: Community-acquired pneumonia (CAP) is the most common infection leading
      to hospitalization in the USA. The objective of this study was to evaluate
      management practices for inpatient CAP in relation to Infectious Diseases Society
      of America/American Thoracic Society (IDSA/ATS) guidelines to identify
      opportunities for antibiotic and health care resource stewardship. METHODS: This
      was a retrospective cohort study of adults hospitalized for CAP at a single
      institution from 15 April 2008 to 31 May 2009. RESULTS: Of the 209 patients with
      CAP who presented to Denver Health Medical Center during the study period and
      were hospitalized, 166 (79 %) and 43 (21 %) were admitted to a medical ward and
      the intensive care unit (ICU), respectively. Sixty-one (29 %) patients were
      candidates for outpatient therapy per IDSA/ATS guidance with a CURB-65 score of 0
      or 1 and absence of hypoxemia. Sputum cultures were ordered for 110 specimens;
      however, an evaluable sample was obtained in only 49 (45 %) cases. Median time
      from antibiotic initiation to specimen collection was 11 [interquartile range
      (IQR) 6-19] h, and a potential pathogen was identified in only 18 (16 %)
      cultures. Blood cultures were routinely obtained for both non-ICU (81 %) and ICU
      (95 %) cases, but 15 of 36 (42 %) positive cultures were false-positive results.
      The most common antibiotic regimen was ceftriaxone + azithromycin (182, 87 %
      cases). Discordant with IDSA/ATS recommendations, oral step-down therapy
      consisted of a new antibiotic class in 120 (66 %), most commonly levofloxacin
      (101, 55 %). Treatment durations were typically longer than suggested with a
      median of 10 (IQR 8-12) days. CONCLUSIONS: In this cohort of patients
      hospitalized for CAP, management was frequently inconsistent with IDSA/ATS
      guideline recommendations, revealing potential targets to reduce unnecessary
      antibiotic and healthcare resource utilization.

PMID- 23160838
TI  - Testicular involvement during Toscana virus infection: an unusual manifestation?

PMID- 23160841
TI  - Guest editorial introduction to the Special Issue on bio-hybrid systems and
      living machines.

PMID- 23160839
TI  - A review of the physiology of fever in birds.
AB  - While fever is known to occur in invertebrates and vertebrates, the mechanisms of
      fever in animals other than mammals have received scant attention. We look
      initially at the recognition, by the avian immune system, of pathogen associated
      molecular patterns and the likely role of toll-like receptors in signaling the
      presence of bacteria and viruses. Several mediators of fever are subsequently
      released by immune cells, including interleukin-6 and interleukin-1beta, that
      eventually reach the brain and alter thermoregulatory function. As is the case in
      mammals, prostaglandins appear to be the ultimate mediators of fever in birds,
      since the febrile response is attenuated when prostaglandin synthesis is
      inhibited. Ambient temperature modulates the fever response, with larger fevers
      at higher, and smaller fevers at lower ambient temperatures. Glucocorticoid
      levels are increased during fever and seem to play an important role by
      modulating the extent of fever generation, possibly playing a role in the
      attenuation of fever after repeated exposure to a pathogen in a process termed
      tolerance, suggesting that the fever process can be phenotypically adapted to
      likely future conditions. While fever has an ancient phylogenetic history and
      many of the underling mechanisms in birds appear similar to mammals, there are
      several important differences that suggest fever has evolved quite differently in
      these two homeothermic classes.

PMID- 23160840
TI  - HIV/STI risk among venue-based female sex workers across the globe: a look back
      and the way forward.
AB  - Female sex workers (FSWs) continue to represent a high-risk population in need of
      targeted HIV prevention interventions. Targeting environmental risk factors
      should result in more sustainable behavior change than individual-level
      interventions alone. There are many types of FSWs who operate in and through a
      variety of micro- (eg, brothels) and macro-level (eg, being sex-trafficked)
      contexts. Efforts to characterize FSWs and inform HIV prevention programs have
      often relied on sex work typologies or categorizations of FSWs by venue or type.
      We conducted a systematic search and qualitatively reviewed 37 published studies
      on venue-based FSWs to examine the appropriateness of sex work typologies, and
      the extent to which this research has systematically examined characteristics of
      different risk environments. We extracted information on study characteristics
      like venue comparisons, HIV/STI prevalence, and sampling strategies. We found
      mixed results with regards to the reliability of typologies in predicting HIV/STI
      infection; relying solely on categorization of FSWs by venue or type did not
      predict seroprevalence in a consistent manner. Only 65 % of the studies that
      allowed for venue comparisons on HIV/STI prevalence provided data on venue
      characteristics. The factors that were assessed were largely individual-level FSW
      factors (eg, demographics, number of clients per day), rather than social and
      structural characteristics of the risk environment. We outline a strategy for
      future research on venue-based FSWs that ultimately aims to inform structural
      level HIV interventions for FSWs.

PMID- 23160842
TI  - hERG drug response measured in droplet bilayers.
AB  - We show measurements of the human cardiac potassium ion channel Kv11.1 (hERG) in
      droplet bilayers incorporated directly from commercial membrane preparations of
      HEK293 cells. Although we do not obtain ensemble conductance kinetics and
      rectification observed in patch clamp measurements of hERG, ensemble currents
      measured in our system showed inhibition dependent on astemizole and E-4031
      concentration, with IC50 values similar to those found with patch clamp. The
      availability of engineered HEK cells expressing a variety of ion channels,
      combined with the simplicity of the inhibition measurement, suggest that droplet
      bilayers may have considerable technological potential for determination of ion
      channel drug potency.

PMID- 23160843
TI  - Scaffold architecture determines chondrocyte response to externally applied
      dynamic compression.
AB  - It remains unclear how specific mechanical signals generated by applied dynamic
      compression (DC) regulate chondrocyte biosynthetic activity. It has previously
      been suggested that DC-induced interstitial fluid flow positively impacts
      cartilage-specific matrix production. Modifying fluid flow within dynamically
      compressed hydrogels therefore represents a promising approach to controlling
      chondrocyte behavior, which could potentially be achieved by changing the
      construct architecture. The objective of this study was to first determine the
      influence of construct architecture on the mechanical environment within
      dynamically compressed agarose hydrogels using finite element (FE) modeling and
      to then investigate how chondrocytes would respond to this altered environment.
      To modify construct architecture, an array of channels was introduced into the
      hydrogels. Increased magnitudes of fluid flow were predicted in the periphery of
      dynamically compressed solid hydrogels and also around the channels in the
      dynamically compressed channeled hydrogels. DC was found to significantly
      increase sGAG synthesis in solid constructs, which could be attributed at least
      in part to an increase in DNA. DC was also found to preferentially increase
      collagen accumulation in regions of solid and channeled constructs where FE
      modeling predicted higher levels of fluid flow, suggesting that this stimulus is
      important for promoting collagen production by chondrocytes embedded in agarose
      gels. In conclusion, this study demonstrates how the architecture of cell-seeded
      scaffolds or hydrogels can be modified to alter the spatial levels of biophysical
      cues throughout the construct, leading to greater collagen accumulation
      throughout the engineered tissue rather than preferentially in the construct
      periphery. This system also provides a novel approach to investigate how
      chondrocytes respond to altered levels of biophysical stimulation. 

PMID- 23160844
TI  - Influence of tissue- and cell-scale extracellular matrix distribution on the
      mechanical properties of tissue-engineered cartilage.
AB  - The insufficient load-bearing capacity of today's tissue- engineered (TE)
      cartilage limits its clinical application. Generally, cartilage TE studies aim to
      increase the extracellular matrix (ECM) content, as this is thought to determine
      the load-bearing properties of the cartilage. However, there are apparent
      inconsistencies in the literature regarding the correlation between ECM content
      and mechanical properties of TE constructs. In addition to the amount of ECM, the
      spatial inhomogeneities in ECM distribution at the tissue scale as well as at the
      cell scale may affect the mechanical properties of TE cartilage. The relative
      importance of such structural inhomogeneities on mechanical behavior of TE
      cartilage is unknown. The aim of the present study was, therefore, to
      theoretically elucidate the influence of these inhomogeneities on the mechanical
      behavior of chondrocyte-agarose TE constructs. A validated non-linear fiber
      reinforced poro-elastic swelling cartilage model that can accommodate for effects
      of collagen reinforcement and swelling by proteoglycans was used. At the tissue
      scale, ECM was gradually varied from predominantly localized in the periphery of
      the TE construct toward an ECM-rich inner core. The effect of these
      inhomogeneities in relation to the total amount of ECM was also evaluated. At the
      cell scale, ECM was gradually varied from localized in the pericellular area,
      toward equally distributed throughout the interterritorial area. Results from the
      tissue-scale model indicated that localization of ECM in either the construct
      periphery or in the inner core may reduce construct stiffness compared with that
      of constructs with homogeneous ECM. Such effects are more significant at high ECM
      amounts. At the cell scale, localization of ECM around the cells significantly
      reduced the overall stiffness, even at low ECM amounts. The compressive stiffness
      gradually increased when ECM distribution became more homogeneous and the osmotic
      swelling pressure in the interterritorial area increased. We conclude that for
      the same amount of ECM content in TE cartilage constructs, superior mechanical
      properties can be achieved with more homogeneous ECM distribution at both tissue
      and cell scale. Inhomogeneities at the cell scale are more important than those
      at the tissue scale. 

PMID- 23160845
TI  - Twist buckling behavior of arteries.
AB  - Arteries are often subjected to torsion due to body movement and surgical
      procedures. While it is essential that arteries remain stable and patent under
      twisting loads, the stability of arteries under torsion is poorly understood. The
      goal of this work was to experimentally investigate the buckling behavior of
      arteries under torsion and to determine the critical buckling torque, the
      critical buckling twist angle, and the buckling shape. Porcine common carotid
      arteries were slowly twisted in vitro until buckling occurred while subjected to
      a constant axial stretch ratio (1.1, 1.3, 1.5 (in vivo level) and 1.7) and lumen
      pressure (20, 40, 70 and 100 mmHg). Upon buckling, the arteries snapped to form a
      kink. For a group of six arteries, the axial stretch ratio significantly affected
      the critical buckling torque ([Formula: see text]) and the critical buckling
      twist angle ([Formula: see text]). Lumen pressure also significantly affected the
      critical buckling torque ([Formula: see text]) but had no significant effect on
      the critical twist angle ([Formula: see text]). Convex material constants for a
      Fung strain energy function were determined and fit well with the axial force,
      lumen pressure, and torque data measured pre-buckling. The material constants are
      valid for axial stretch ratios, lumen pressures, and rotation angles of 1.3-1.5,
      20-100 mmHg, and 0-270[Formula: see text], respectively. The current study
      elucidates the buckling behavior of arteries under torsion and provides new
      insight into mechanical instability of blood vessels. 

PMID- 23160846
TI  - Determinants of anterior knee pain following total knee replacement: a systematic
      review.
AB  - PURPOSE: Anterior knee pain (AKP) following total knee replacement (TKR) is both
      prevalent and clinically relevant. The purpose of this study was to
      systematically review the peer-reviewed literature, and to identify and assess
      the different modifiable and non-modifiable determinants that may be associated
      with the development of AKP in patients following primary TKR. METHODS: A
      systematic computerized database search (Cochrane Database of Systematic Reviews,
      Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, and Google
      Scholar) was performed in January 2012. The quality of the studies was assessed
      using the GRADE approach. RESULTS: A total of 54 articles met the inclusion
      criteria. Variables that have been researched with regard to the prevalence of
      AKP include patient and knee-specific characteristics, prosthetic design,
      operative technique, treatment of the patella, and time of assessment. A weak
      correlation with AKP was found for specific retained presurgery gait patterns. A
      weak recommendation can be given for the use of femoral components with a
      posterior centre of rotation, resection of Hoffa's fat pad, patellar rim
      electrocautery, and preventing combined component internal rotation. The
      correlation between postsurgical AKP and the degree of patellar cartilage wear,
      tibial component bearing strategies, and patellar resurfacing is inconclusive.
      Due to substantial heterogeneity of the included studies, no meta-analysis was
      performed. CONCLUSIONS: No single variable is likely to explain the differences
      in the reported rates of AKP, although variables leading to abnormal
      patellofemoral joint loading appear to be of special significance. LEVEL OF
      EVIDENCE: III.

PMID- 23160847
TI  - Tibial avulsion fracture of the posterior root of the medial meniscus in
      children.
AB  - Few reports have described avulsion fractures of the posterior root of the medial
      meniscus in skeletally immature patients. This lesion should not be overlooked as
      it damages the load absorptive (distributive) function of the meniscus,
      increasing the risk of cartilage degeneration. Two cases of displaced avulsion
      fractures of the posterior root of the medial meniscus in children are presented
      along with a concise report of the literature regarding avulsion fractures of the
      posterior root of the medial meniscus. Both avulsions were reattached
      arthroscopically by trans-tibial pull-out sutures with a good clinical result at
      2-years follow-up, and in one case, the avulsion was found at re-arthroscopy
      after 6 weeks to have healed.

PMID- 23160848
TI  - Meniscectomy leads to early changes in the mineralization distribution of
      subchondral bone plate.
AB  - PURPOSE: It is generally recognized that the subchondral bone plate (SBP) is
      involved in development of osteoarthritis (OA). However, the pathophysiological
      significance is not yet clear. The goal of this study is to investigate the
      extent of the changes that occur in SBP of the tibial plateau in the early stages
      of experimental OA. METHODS: Forty-three female rabbits were assigned to 5
      experimental (n = 8 each group) and one sham group (n = 3). OA was induced by
      medial meniscectomy in the right knee, the left knee served as control. 2, 4, 8,
      12, and 24 weeks after meniscectomy, cartilage damage was evaluated, and bone
      mineral density (BMD) and mineralization distribution of the SBP was measured by
      computed tomography osteoabsorptiometry (CT-OAM). RESULTS: Cartilage damage
      started 2 weeks after meniscectomy with surface roughening. Cartilage defects
      increased over time. 24 weeks postoperatively, subchondral bone was exposed. As
      early as 2 weeks after meniscectomy, BMD in the medial tibial plateau decreased
      significantly. BMD increased again and reached the values of the non-operated
      knee 12 weeks postoperatively. In addition, already 4 weeks after meniscectomy a
      significant shift of the density maximum on the medial tibial plateau, which is
      normally centrally located toward the margin was observed. CONCLUSIONS: In
      conclusion, the results of this study contribute to the concept of early
      involvement of the SBP in the development of OA. The hypothesis that changes in
      the SBP occur simultaneously to cartilage damage was confirmed.

PMID- 23160849
TI  - Population at high-risk of indoor heatstroke: the usage of cooling appliances
      among urban elderlies in Japan.
AB  - OBJECTIVES: Heatstroke due to a heat wave during the summer is one of the
      commonly known health impacts of climate change in Japan. The elderly are
      particularly at high-risk of developing indoor heatstroke with poor prognosis.
      This study aims to describe the population among elderlies at high-risk of indoor
      heatstroke by focusing on the usage of cooling appliances. METHODS: We conducted
      a web-based household survey in eight urban areas during the winter season of
      2011. Households with a person aged 65 and over were selected as samples from
      panel members of a research firm, and the oldest member of the household was
      queried about his/her usage of cooling appliances. The population at high-risk of
      indoor heatstroke is defined as the elderly staying in a room without cooling
      appliances, or not using the installed cooling appliances, or turning the cooling
      appliances on only when the room temperature is above 28  degrees C. RESULTS:
      15.4 and 19.1 % of the elderlies living in urban areas of Japan are identified as
      at high-risk of indoor heatstroke during activity time and sleeping time,
      respectively, according to the definition of high-risk of indoor heatstroke in
      this study. CONCLUSIONS: These figures are not negligible since the consequences
      of heatstroke are grave, but its risk can be eliminated by an appropriate usage
      of cooling appliances. The preventive interventions are needed to protect the
      elderlies at high-risk of heatstroke.

PMID- 23160850
TI  - Relationship between lifestyle and lifestyle-related factors in a rural-urban
      population of Japan.
AB  - OBJECTIVE: To clarify the actual state of residents' lifestyle in a mixed rural
      urban area in Japan, and to investigate the relationship between residents'
      lifestyle and lifestyle-related factors. METHODS: The Japanese version of Health
      Promoting Lifestyle Profile-II (HPLP-II), lifestyle-related factors developed
      through group work with residents of Town A, and demographic variables were used
      to evaluate 1176 community residents' lifestyles and associated factors. RESULTS:
      Factor analysis revealed that there were 4 factors related to healthy lifestyle.
      Nonparametric analysis revealed that female and elderly groups showed higher
      overall HPLP-II score than male and young groups. A significant correlation
      coefficient was seen between scores of overall HPLP-II and lifestyle-related
      factors (r = 0.611, p < 0.001). Multiple linear regression analysis demonstrated
      that HPLP-II was significantly associated with each lifestyle-related factor,
      showing a similar order in both gender and age groups. Finally, covariance
      structure analysis demonstrated that the score of health cognition and regional
      factors increased the score of HPLP-II, which then increased the score of self
      rated health. CONCLUSIONS: The present research clarified the actual state of
      residents' lifestyles by age and gender in a mixed rural-urban area in Japan,
      demonstrating a vector model from health cognition and regional factors to self
      rated health, via residents' lifestyle.

PMID- 23160852
TI  - Extensive structural change of the envelope protein of dengue virus induced by a
      tuned ionic strength: conformational and energetic analyses.
AB  - The Dengue has become a global public health threat, with over 100 million
      infections annually; to date there is no specific vaccine or any antiviral drug.
      The structures of the envelope (E) proteins of the four known serotype of the
      dengue virus (DENV) are already known, but there are insufficient molecular
      details of their structural behavior in solution in the distinct environmental
      conditions in which the DENVs are submitted, from the digestive tract of the
      mosquito up to its replication inside the host cell. Such detailed knowledge
      becomes important because of the multifunctional character of the E protein: it
      mediates the early events in cell entry, via receptor endocytosis and, as a class
      II protein, participates determinately in the process of membrane fusion. The
      proposed infection mechanism asserts that once in the endosome, at low pH, the E
      homodimers dissociate and insert into the endosomal lipid membrane, after an
      extensive conformational change, mainly on the relative arrangement of its three
      domains. In this work we employ all-atom explicit solvent Molecular Dynamics
      simulations to specify the thermodynamic conditions in that the E proteins are
      induced to experience extensive structural changes, such as during the process of
      reducing pH. We study the structural behavior of the E protein monomer at acid pH
      solution of distinct ionic strength. Extensive simulations are carried out with
      all the histidine residues in its full protonated form at four distinct ionic
      strengths. The results are analyzed in detail from structural and energetic
      perspectives, and the virtual protein movements are described by means of the
      principal component analyses. As the main result, we found that at acid pH and
      physiological ionic strength, the E protein suffers a major structural change;
      for lower or higher ionic strengths, the crystal structure is essentially
      maintained along of all extensive simulations. On the other hand, at basic pH,
      when all histidine residues are in the unprotonated form, the protein structure
      is very stable for ionic strengths ranging from 0 to 225 mM. Therefore, our
      findings support the hypothesis that the histidines constitute the hot points
      that induce configurational changes of E protein in acid pH, and give extra
      motivation to the development of new ideas for antivirus compound design.

PMID- 23160853
TI  - Phase I/II study of the tumour-targeting human monoclonal antibody-cytokine
      fusion protein L19-TNF in patients with advanced solid tumours.
AB  - PURPOSE: L19-TNF is an armed antibody that selectively targets human TNF to extra
      domain B-fibronectin on tumour blood vessels. We performed a phase I/II first-in
      man trial with L19-TNF monotherapy in metastatic solid cancer patients to study
      safety and signs of clinical activity. METHODS: Six cohorts of patients were
      treated with increasing (1.3-13 MUg/kg) doses of intravenous L19-TNF on day 1, 3,
      and 5 of repeated 3-weekly cycles, and 12 colorectal cancer patients were treated
      at 13 MUg/kg. PK, antibody formation, changes in lymphocyte subsets, 5-HIAA
      plasma levels as well as safety and clinical activity were analysed. RESULTS:
      Thirty-four patients received at least one L19-TNF dose. The serum half-life of
      L19-TNF at 13 MUg/kg was 33.6 min, and maximum peak serum concentration was 73.14
      MUg/L. Mild chills, nausea and vomiting but no haemato- or unexpected toxicity
      were observed. Grade 3 lumbar pain in bone metastasis was the only dose-limiting
      toxicity found in one patient. Objective tumour responses were not detected.
      Transient stable disease occurred in 19 of 31 evaluable patients. CONCLUSIONS:
      Intravenous L19-TNF on day 1, 3, and 5 of a 3-weekly schedule was safe up to 13
      MUg/kg, but did not result in objective tumour responses. The maximally tolerated
      dose (MTD) was not reached, allowing for further dose escalation of L19-TNF
      possibly in combination with chemotherapy.

PMID- 23160854
TI  - WT1 peptide immunotherapy for gynecologic malignancies resistant to conventional
      therapies: a phase II trial.
AB  - OBJECTIVE: The aim of the present study was to analyze the long-term survival
      effects of WT1 peptide vaccine, in addition to its anti-tumor effects and
      toxicity. METHODS: A phase II clinical trial was conducted during the period of
      2004-2010 at Osaka University Hospital, Osaka, Japan. The patients who had
      gynecologic malignancies progressing against previous treatments received WT1
      peptide vaccine intradermally at 1-week intervals for 12 weeks. The vaccination
      was allowed to further continue, unless the patient's condition became
      significantly worse due to the disease progression. RESULTS: Forty out of 42
      patients, who met all the inclusion criteria, underwent WT1 peptide vaccine.
      Among these 40 patients, stable disease was observed in 16 cases (40 %). Skin
      toxicity of a grade 1, 2 and 3 occurred in 25 cases (63 %), 9 cases (23 %) and a
      single case (3 %), respectively, and liver toxicity of grade 1 in a single case
      (3 %). The overall survival period was significantly longer in cases positive for
      the WT1 peptide-specific delayed-type hypersensitivity (DTH) reaction after the
      vaccination, compared to those negative for the DTH reaction (p = 0.023).
      Multivariate Cox proportional hazards analysis demonstrated that the adjusted
      hazard ratio for the negative DTH reaction was 2.73 (95 % CI 1.04-7.19, p =
      0.043). CONCLUSION: WT1 peptide vaccine may be a potential treatment, with
      limited toxicity, for gynecologic malignancies that have become resistant to
      conventional therapies. Larger scale of clinical studies is required to establish
      the efficacy of the WT1 peptide vaccine for gynecologic malignancies.

PMID- 23160851
TI  - Wnt signaling: role in Alzheimer disease and schizophrenia.
AB  - Wnt signaling function starts during the development of the nervous system and is
      crucial for synaptic plasticity in the adult brain. Clearly Wnt effects in
      synaptic and plastic processes are relevant, however the implication of this
      pathway in the prevention of neurodegenerative diseases that produce synaptic
      impairment, is even more interesting. Several years ago our laboratory found a
      relationship between the loss of Wnt signaling and the neurotoxicity of the
      amyloid-beta-peptide (Abeta), one of the main players in Alzheimer's disease
      (AD). Moreover, the activation of the Wnt signaling cascade prevents Abeta
      dependent cytotoxic effects. In fact, disrupted Wnt signaling may be a direct
      link between Abeta-toxicity and tau hyperphosphorylation, ultimately leading to
      impaired synaptic plasticity and/or neuronal degeneration, indicating that a
      single pathway can account for both neuro-pathological lesions and altered
      synaptic function. These observations, suggest that a sustained loss of Wnt
      signaling function may be a key relevant factor in the pathology of AD. On the
      other hand, Schizophrenia remains one of the most debilitating and intractable
      illness in psychiatry. Since Wnt signaling is important in organizing the
      developing brain, it is reasonable to propose that defects in Wnt signaling could
      contribute to Schizophrenia, particularly since the neuro-developmental
      hypothesis of the disease implies subtle dys-regulation of brain development,
      including some core components of the Wnt signaling pathways such as GSK-3beta or
      Disrupted in Schizophrenia-1 (DISC-1). This review focuses on the relationship
      between Wnt signaling and its potential relevance for the treatment of
      neurodegenerative and neuropsychiatric diseases including AD and Schizophrenia.

PMID- 23160856
TI  - Can our understanding of informed consent be strengthened using the idea of
      cluster concepts?
AB  - Informed consent is thought to exist as a well-defined entity. Altered concepts
      of patient autonomy, differential cultural understanding of the entity, and the
      failure of clients to distinguish between research and clinical ethics, and
      various hierarchical cultural views of informed consent all suggest that
      alterations may be needed in the traditional concept. By using the methodology
      outlined by Gasking in which he defines the idea of "cluster concepts," one may
      be able to enlarge the definition and augment the understanding of the informed
      consent and include the time and culture-specific variants which exist. 

PMID- 23160855
TI  - Practicing physiotherapy in Danish private practice: an ethical perspective.
AB  - Despite an increasingly growth of professional guidelines, textbooks and research
      about ethics in health care, awareness about ethics in Danish physiotherapy
      private practice seen vague. This article explores how physiotherapists in Danish
      private practice, from an ethical perspective, perceive to practice
      physiotherapy. The empirical data consists of interviews with twenty-one
      physiotherapists. The interviews are analysed from a hermeneutic approach,
      inspired by Ricoeur's textual interpretation of distanciation. The analysis
      follows three phases: naive reading, structural analysis and comprehensive
      analysis. Four main themes are constructed: Beneficence as the driving force;
      Disciplining the patient through the course of physiotherapy; Balancing between
      being a trustworthy professional and a businessperson; The dream of a code of
      practice. Private practice physiotherapy is embedded in a structural frame
      directed by both political and economical conditions that shape the conditions
      for practicing physiotherapy. It means that beneficence in practice is a balance
      between the patient, the physiotherapists themselves and the business.
      Beneficence towards the patient is expressed as an implicit demand.
      Physiotherapeutic practice is expressed as being an integration of
      professionalism and personality which implies that the physiotherapists also have
      to benefit themselves. Private practice seems to be driven by a paternalistic
      approach towards the patient, where disciplining the patient is a crucial element
      of practice, in order to optimise profit. Physiotherapists wish for a more
      beneficent practice in the future by aiming at bridging 'to be' and 'ought to
      be'.

PMID- 23160857
TI  - The relative importance of undesirable truths.
AB  - The right not to know is often defended on the basis of the principle of respect
      for personal autonomy. If I choose not to acquire personal information that
      impacts on my future prospects, such a choice should be respected, because I
      should be able to decide whether to access information about myself and how to
      use it. But, according to the incoherence objection to the right not to know in
      the context of genetic testing, the choice not to acquire genetic information
      undermines the capacity for autonomous decision making. The claim is that it is
      incoherent to defend a choice that is inimical to autonomy by appealing to
      autonomy. In this paper, I suggest that the choice not to know in the context of
      genetic testing does not undermine self-authorship, which is a key aspect of
      autonomous decision making. In the light of this, the incoherence objection to
      the right not to know seems less compelling. 

PMID- 23160858
TI  - Mid-term results of small-sized St. Jude Medical Regent prosthetic valves (21 mm
      or less) for small aortic annulus.
AB  - Prosthesis-patient mismatch (PPM) is always of concern when performing aortic
      valve replacement (AVR) in patients with a small aortic annulus. Although
      bioprosthetic AVR is preferred in patients older than 65 years, we have
      experienced cases in elderly patients with a small aortic annulus whereby we
      could not implant small-sized bioprosthetic valves. We have implanted St. Jude
      Medical Regent (SJMR) mechanical valves (St. Jude Medical, St. Paul, MN, USA) as
      necessary, even in elderly patients with no aortic annulus enlargement. We
      investigated our experiences of AVR with SJMR mechanical valves of 21 mm or less
      in size. Between January 2006 and December 2009, 40 patients underwent AVR with
      SJMR mechanical valves <=21 mm in size: 9 patients received 21-mm valves, 19
      received 19-mm valves, and 12 received 17-mm valves. The mean age was 65.9 +/-
      9.5 years, and 25 patients (62.5 %) were 65 years or older. We evaluated the
      clinical outcome and the echocardiographic data for each valve size. There was no
      operative or hospital mortality. The mean duration of clinical follow-up was 31.2
      +/- 17.6 months. During follow-up, there were no hospitalizations due to heart
      failure. The cumulative valve-related event-free survival was 93 % at 33 months,
      and the cumulative hemorrhagic event-free survival was 93 % at 33 months and 84 %
      at 43 months, using the Kaplan-Meier method. At follow-up, the mean values of the
      measured effective orifice area (EOA) for the 21-, 19-, and 17-mm prostheses were
      2.00 +/- 0.22, 1.74 +/- 0.37, and 1.25 +/- 0.26 cm(2), and the mean measured EOA
      index (EOAI) were 1.17 +/- 0.12, 1.11 +/- 0.21 and 0.90 +/- 0.22 cm(2)/m(2),
      respectively. A PPM (EOAI <=0.85) was documented in 5 patients, all of whom had
      received a 17-mm SJMR valve. AVR with SJMR valves of 21 mm or less in size
      appears to show satisfactory clinical and hemodynamic results. 

PMID- 23160859
TI  - Abnormal P-wave terminal force in lead V1 is associated with cardiac death or
      hospitalization for heart failure in prior myocardial infarction.
AB  - The aim of this study was to clarify the prognostic significance of P-wave
      terminal force in lead V1 (PTFV1) in patients with prior myocardial infarction
      (MI). We retrospectively examined 185 patients with prior MI. The primary end
      point was cardiac death or hospitalization for heart failure. Abnormal PTFV1 was
      defined as PTFV1 >= 40 mm * ms. During a follow-up period of 6.4 +/- 2.9 years,
      39 patients developed the primary end point. A Kaplan-Meier analysis showed a
      lower primary event-free rate in 79 patients with abnormal PTFV1 than in 106
      patients with normal PTFV1 (P < 0.001). When we classified 79 patients with
      abnormal PTFV1 into 31 with a purely negative P wave in lead V1 and 48 with a
      biphasic negative P wave in lead V1, the primary event-free rate did not differ
      between the two groups of patients. A multivariate Cox regression analysis
      selected age (hazard ratio (HR) 1.09, 95 % confidence interval (CI) 1.04-1.14, P
      < 0.001), multivessel coronary disease (HR 2.33, 95 % CI 1.02-5.28, P = 0.04),
      and abnormal PTFV1 (HR 2.72, 95 % CI 1.24-5.99, P = 0.01) as independent
      predictors of the primary end point. In conclusion, abnormal PTFV1 is an
      independent predictor of cardiac death or hospitalization for heart failure in
      patients with prior MI. The analysis of P waves in lead V1 should provide useful
      prognostic information in patients with prior MI. 

PMID- 23160860
TI  - Climate change and human health: a One Health approach.
AB  - Climate change adds complexity and uncertainty to human health issues such as
      emerging infectious diseases, food security, and national sustainability planning
      that intensify the importance of interdisciplinary and collaborative research.
      Collaboration between veterinary, medical, and public health professionals to
      understand the ecological interactions and reactions to flux in a system can
      facilitate clearer understanding of climate change impacts on environmental,
      animal, and human health. Here we present a brief introduction to climate science
      and projections for the next century and a review of current knowledge on the
      impacts of climate-driven environmental change on human health. We then turn to
      the links between ecological and evolutionary responses to climate change and
      health. The literature on climate impacts on biological systems is rich in both
      content and historical data, but the connections between these changes and human
      health is less understood. We discuss five mechanisms by which climate changes
      impacts on biological systems will be felt by the human population: Modifications
      in Vector, Reservoir, and Pathogen Lifecycles; Diseases of Domestic and Wild
      Animals and Plants; Disruption of Synchrony Between Interacting Species; Trophic
      Cascades; and Alteration or Destruction of Habitat. Each species responds to
      environmental changes differently, and in order to predict the movement of
      disease through ecosystems, we have to rely on expertise from the fields of
      veterinary, medical, and public health, and these health professionals must take
      into account the dynamic nature of ecosystems in a changing climate. 

PMID- 23160861
TI  - The application of one health approaches to henipavirus research.
AB  - Henipaviruses cause fatal infection in humans and domestic animals. Transmission
      from fruit bats, the wildlife reservoirs of henipaviruses, is putatively driven
      (at least in part) by anthropogenic changes that alter host ecology. Human and
      domestic animal fatalities occur regularly in Asia and Australia, but recent
      findings suggest henipaviruses are present in bats across the Old World tropics.
      We review the application of the One Health approach to henipavirus research in
      three locations: Australia, Malaysia and Bangladesh. We propose that by
      recognising and addressing the complex interaction among human, domestic animal
      and wildlife systems, research within the One Health paradigm will be more
      successful in mitigating future human and domestic animal deaths from henipavirus
      infection than alternative single-discipline approaches. 

PMID- 23160862
TI  - Expression and localization of inhibitor of differentiation (ID) proteins during
      tissue and vascular remodelling in the human corpus luteum.
AB  - Members of the transforming growth factor-beta (TGF-beta) superfamily are likely
      to have major roles in the regulation of tissue and vascular remodelling in the
      corpus luteum (CL). There are four inhibitor-of-differentiation (ID1-4) genes
      that are regulated by members of the TGF-beta superfamily and are involved in the
      transcriptional regulation of cell growth and differentiation. We studied their
      expression, localization and regulation in dated human corpora lutea from across
      the luteal phase (n = 22) and after human chorionic gonadotrophin (hCG)
      administration in vivo (n = 5), and in luteinized granulosa cells (LGCs), using
      immunohistochemistry and quantitative RT-PCR. ID1-4 can be localized to multiple
      cell types in the CL across the luteal phase. Endothelial cell ID3 (P < 0.05) and
      ID4 (P < 0.05) immunostaining intensities peak at the time of angiogenesis but
      overall ID1 (P < 0.05) and ID3 (P < 0.05) expression peaks at the time of
      luteolysis, and luteal ID3 expression is inhibited by hCG in vivo (P < 0.01). In
      LGC cultures in vitro, hCG had no effect on ID1, down-regulated ID3 (P < 0.001),
      and up-regulated ID2 (P < 0.001) and ID4 (P < 0.01). Bone morphogenic proteins
      (BMPs) had no effect on ID4 expression but up-regulated ID1 (P < 0.01 to P <
      0.005). BMP up-regulation of ID2 (P < 0.05) was additive to the hCG up-regulation
      of ID2 expression (P < 0.001), while BMP cancelled out the down regulative effect
      of hCG on ID3 regulation. As well as documenting regulation patterns specific for
      ID1, ID2, ID3 and ID4, we have shown that IDs are located and differentially
      regulated in the human CL, suggesting a role in the transcriptional regulation of
      luteal cells during tissue and vascular remodelling.

PMID- 23160863
TI  - Asthma education in the student laboratory.
AB  - The Integrated Pharmacy Skills Laboratory (IPSL) at South University School of
      Pharmacy is dedicated to providing future pharmacists with the necessary
      knowledge and skills to care for asthma patients. Asthma is a chronic respiratory
      disorder that is characterized by airway inflammation, hyper responsive airways,
      and bronchoconstriction. It affects more than 30 million people and accounts for
      $30 billion in health care costs. Therefore, it is vital for our students to be
      educated in asthma management including medications and devices to improve
      patient outcomes. Students, as future pharmacist, learn to manage asthma patients
      in the community setting, the hospital setting, and the clinic setting through
      various laboratory experiences.

PMID- 23160864
TI  - Treatment of dabigatran-associated bleeding: case report and review of the
      literature.
AB  - Dabigatran etexilate is a competitive, direct thrombin inhibitor that works in
      the coagulation cascade to ultimately prevent thrombus formation. It is
      recommended by the 2012 American College of Chest Physicians evidence-based
      clinical practice guidelines as first-line therapy over vitamin k antagonists for
      long-term antithrombotic therapy in patients with paroxysmal or persistent
      nonrheumatic atrial fibrillation who are at intermediate to high risk of stroke
      and systemic embolism (grade 2B). However, serious postmarketing events involving
      life-threatening bleeding are emerging with no antidote for reversal of the
      anticoagulant effect being available for use. Potential reversal agents are being
      used in clinical practice with questionable efficacy and safety profiles. We
      report a case involving an 84-year-old male with acute kidney injury who
      developed life-threatening gastrointestinal and surgical site bleeding secondary
      to dabigatran accumulation. Use of the Naranjo probability scale indicated a
      probable cause between the bleeding event and dabigatran use. After
      discontinuation of drug therapy, fresh frozen plasma, recombinant coagulation
      factor VIIa, and cryoprecipitate were administered as potential reversal agents
      with negligible benefit. However, this patient appeared to slowly benefit with
      administration of continuous venovenous hemodialysis. Based upon our experience
      with this patient and literature review, the most effective treatment algorithm
      for dabigatran-associated bleeding may be to utilize hemodialysis initially.

PMID- 23160865
TI  - Contemporary Anticoagulation Reversal    Focus on Direct Thrombin Inhibitors and
      Factor Xa Inhibitors.
AB  - Several oral direct thrombin inhibitors (DTIs) and factor Xa (FXa) inhibitors
      have recent Food and Drug Administration approval or are under investigation in
      late-stage clinical trials for the prevention and treatment of thromboembolic
      events. Rapid reversal of anticoagulation is typically recommended in patients
      with severe or life-threatening bleeding and in patients requiring surgery or
      invasive procedures. However, no antidote exists for DTIs or FXa inhibitors
      though replacement of coagulation factors using clotting factor concentrates is
      routinely considered in some clinical scenarios. Clotting factor concentrates
      available in the United States include prothrombin complex concentrate, activated
      prothrombin complex concentrate, and recombinant factor VII, activated.
      Coagulation tests to confirm adequate reversal of anticoagulation should be
      considered and commonly include activated partial thromboplastin time and
      thrombin time (TT) for DTIs, and chromogenic FXa assay and TT for FXa inhibitors.
      Monitoring of coagulation tests should continue for 1 to 2 days after achievement
      of hemostasis, since the duration of the clotting factor concentrate may be
      shorter than the oral anticoagulant, especially in patients with organ
      dysfunction. Utilization of decision-support tools and use of standardized
      reversal protocols are recommended to prevent errors in prescribing and
      dispensing for clotting factor concentrates.

PMID- 23160866
TI  - Ovarian tumor characterization and classification using ultrasound-a new online
      paradigm.
AB  - Among gynecological malignancies, ovarian cancer is the most frequent cause of
      death. Image mining algorithms have been predominantly used to give the
      physicians a more objective, fast, and accurate second opinion on the initial
      diagnosis made from medical images. The objective of this work is to develop an
      adjunct computer-aided diagnostic technique that uses 3D ultrasound images of the
      ovary to accurately characterize and classify benign and malignant ovarian
      tumors. In this algorithm, we first extract features based on the textural
      changes and higher-order spectra information. The significant features are then
      selected and used to train and evaluate the decision tree (DT) classifier. The
      proposed technique was validated using 1,000 benign and 1,000 malignant images,
      obtained from ten patients with benign and ten with malignant disease,
      respectively. On evaluating the classifier with tenfold stratified cross
      validation, the DT classifier presented a high accuracy of 97 %, sensitivity of
      94.3 %, and specificity of 99.7 %. This high accuracy was achieved because of the
      use of the novel combination of the four features which adequately quantify the
      subtle changes and the nonlinearities in the pixel intensity variations. The
      rules output by the DT classifier are comprehensible to the end-user and, hence,
      allow the physicians to more confidently accept the results. The preliminary
      results show that the features are discriminative enough to yield good accuracy.
      Moreover, the proposed technique is completely automated, accurate, and can be
      easily written as a software application for use in any computer.

PMID- 23160867
TI  - The role of type 1 angiotensin receptors on T lymphocytes in cardiovascular and
      renal diseases.
AB  - The renin-angiotensin system plays a critical role in the pathogenesis of several
      cardiovascular diseases, largely through activation of type I angiotensin (AT(1))
      receptors by angiotensin II. Treatment with AT(1) receptor blockers (ARBs) is a
      proven successful intervention for hypertension and progressive heart and kidney
      disease. However, the divergent actions of AT(1) receptors on individual cell
      lineages in hypertension may present novel opportunities to optimize the
      therapeutic benefits of ARBs. For example, T lymphocytes make important
      contributions to the induction and progression of various cardiovascular
      diseases, but new experiments indicate that activation of AT(1) receptors on T
      cells paradoxically limits inflammation and target organ damage in hypertension.
      Future studies should illustrate how these discrepant functions of AT(1)
      receptors in target organs versus mononuclear cells can be exploited for the
      benefit of patients with recalcitrant hypertension and other cardiovascular
      diseases.

PMID- 23160869
TI  - Impact of staged InterStim implantation on the postoperative activities of daily
      living and pain.
AB  - OBJECTIVES: To evaluate the short-term effects of staged InterStim implantation
      on activities of daily living (ADL) and pain. METHODS: This prospective study
      assessed women undergoing staged InterStim implantation. The Older Americans
      Resources and Services Program Multidimensional Functional Assessment
      Questionnaire asked participants about their ability to complete activities
      without help or what help they needed following stage I lead placement and stage
      II neurostimulator implantation. Narcotic use and a visual analog scale (VAS) for
      pain were recorded daily. RESULTS: Thirty-eight women underwent stage I with 33
      (86.8%) progressing to stage II. On stage I postoperative day (POD) 2, more women
      required help shopping compared with baseline (40 vs 17%, p < 0.004). The median
      pain score increased on Stage I POD1 (P < 0.001) and the use of narcotics
      increased on POD1 and 2 compared with baseline (50% vs 14%, p = 0.001). The same
      trends were seen following stage II. CONCLUSIONS: Staged InterStim implantation
      has minimal impact on ADL, pain or narcotic requirements.

PMID- 23160868
TI  - Broad-spectrum antifungal-producing lactic acid bacteria and their application in
      fruit models.
AB  - A large-scale screen of some 7,000 presumptive lactic acid bacteria (LAB),
      isolated from animal, human, or plant origin, identified 1,149 isolates with
      inhibitory activity against the food-spoilage mould Penicillium expansum. In
      excess of 500 LAB isolates were subsequently identified to produce a broad
      spectrum of activity against P. expansum, Penicillium digitatum, Penicillium
      notatum, Penicillium roqueforti, Rhizopus stolonifer, Fusarium culmorum,
      Aspergillus fumigatus and Rhodotorula mucilaginosa. Partial 16S rRNA sequencing
      of 94 broad spectrum isolates revealed that the majority of antifungal producers
      were strains of Lactobacillus plantarum. The remaining population was composed of
      Weissella confusa and Pediococcus pentosaceous isolates. Characterization of six
      selected broad-spectrum antifungal LAB isolates revealed that antifungal activity
      is maximal at a temperature of 30  degrees C, a pH of 4.0 and is stable across a
      variety of salt concentrations. The antifungal compound(s) was shown to be
      neither proteinaceous nor volatile in nature. P. pentosaceous 54 was shown to
      have protective properties against P. expansum spoilage when applied in pear,
      plum and grape models, therefore representing an excellent candidate for food
      related applications.

PMID- 23160870
TI  - Prolapse and sexual function 8 years after neovagina according to Shears: a study
      of 43 cases with Mayer-von Rokitansky-Kuster-Hauser syndrome.
AB  - INTRODUCTION AND HYPOTHESIS: To investigate sexual and anatomical outcome after
      Shears neovagina in patients with Mayer-von Rokitansky-Kuster-Hauser syndrome
      (MRKH). METHODS: Forty-three consecutive patients with MRKH syndrome underwent
      surgery creating a neovagina according to Shears. Follow-up was 8 years. Sexual
      function was assessed using the Female Sexual Function Index (FSFI) as patient
      reported outcome; anatomical results were assessed measuring anterior, posterior
      and apical prolapse using the ICS Pelvic Organ Prolapse Score (ICS-POP Score).
      Pelvic floor contraction was measured applying the Oxford grading system.
      RESULTS: Thirty-seven of the patients were regularly sexually active and filled
      in the FSFI; mean total FSFI was 27.2 (range 24-28). No significant prolapse of
      the neovagina was noted, 11 patients had a grade I cystocele, rectocele or apical
      descent that was asymptomatic. Oxford grading of the pelvic floor contraction was
      4 in median (range 2-5). CONCLUSION: The neovagina according to Shears is a
      valuable surgical option with good sexual and anatomical outcome 8 years after
      therapy.

PMID- 23160871
TI  - Guidelines for the management of third and fourth degree perineal tears after
      vaginal birth from the Austrian Urogynecology Working Group.
AB  - The purpose of this guideline is to provide a decision aid for diagnosis,
      treatment, and follow-up of patients with major perineal tears and thus minimize
      the risk of persistent symptoms. In 2007, the "Guideline for the management of
      third and fourth degree perineal tears after vaginal birth" was established by
      members of the Austrian Urogynecologic Working Group (AUB). The guideline was
      updated in 2011, including literature published up to 30 November 2011. The
      DELPHI method was used to reach consensus. Evidence-based and consensus-based
      statements were defined for epidemiology, risk factors, classification,
      diagnosis, surgery, and follow-up of major perineal lacerations at vaginal birth.

PMID- 23160872
TI  - Clinical findings associated with bladder trabeculations in women.
AB  - INTRODUCTION AND HYPOTHESIS: This study evaluated whether bladder trabeculations
      are associated with advanced prolapse, urinary urgency, or detrusor overactivity
      among women undergoing office cystoscopy. It is well established that bladder
      trabeculations are associated with bladder outlet obstruction (BOO) in men;
      however, the clinical significance of trabeculations in women is unclear. Whereas
      an analogous relationship has been proposed between prostatic obstruction in men
      and advanced pelvic organ prolapse (POP) in women, little data in the medical
      literature supports this theory. METHODS: A retrospective cohort study was
      conducted using Current Procedural Terminology (CPT) codes (52000, 52204) to
      identify all women who underwent office cystoscopy at our urogynecology center
      between January 2008 and May 2011. The 551 women identified were grouped by the
      presence or absence of bladder trabeculations. Multivariable logistic regression
      was used to estimate the association between trabeculations and the primary aim,
      increasing stage of prolapse, and the secondary aims: bladder outlet obstruction,
      detrusor overactivity, or urge urinary incontinence (UUI). RESULTS: Of the 551
      women meeting inclusion criteria, 86 had trabeculations. Controlling for age, the
      odds of bladder trabeculations were eightfold greater for women with stage IV POP
      when compared with women with stage 0 prolapse [odds ratio (OR) 8.2, 95%
      confidence interval (CI) 1.6-43.1]. The odds of bladder trabeculations were
      twofold greater for women with detrusor overactivity (OR 2.3, 95% CI 1.3-4.0)
      found on urodynamic study and also as reflected subjectively by answers to Pelvic
      Floor Distress Inventory (PFDI) item number 16 (OR 4.2, 95% CI 1.3-14.5).
      CONCLUSION: In this study, bladder trabeculations were associated with stage IV
      prolapse in the anterior compartment as well as with detrusor overactivity and
      UUI.

PMID- 23160873
TI  - Randomized trial of a comparison of rehabilitation or drug therapy for urgency
      urinary incontinence: 1-year follow-up.
AB  - INTRODUCTION AND HYPOTHESIS: Our goal was to compare the long-term efficacy of
      bladder training (BT), pelvic floor muscle training (PFMT), combined pelvic floor
      rehabilitation (CPFR), and drug therapy (DT) in patients with urgency urinary
      incontinence (UUI). METHODS: This multicenter single-blind randomized controlled
      trial compared the efficacy of BT, PFMT, DT, and CPFR at baseline and 3- and 12
      month follow-ups. Outcome measures included number of voids/24 h, number of UUI
      episodes, Quality of Life related to UUI (QOL-rUI), urogynecologic visual analog
      scale, and self-reported function and disability. RESULTS: A significant
      improvement was found for all treatment groups at 3 and 12 months in urinary
      frequency, UUI episodes, QOL-rUI, and number of daily pads. Only CPFR showed a
      significant decrease of 4 voids/24 h and a significant increase in self-reported
      function. CONCLUSIONS: The study demonstrated long-term benefits of DT, BT, PFMT,
      and CPFR in the treatment of UUI with a slight advantage for CPFR.

PMID- 23160874
TI  - Two neonatal cholestasis patients with mutations in the SRD5B1 (AKR1D1) gene:
      diagnosis and bile acid profiles during chenodeoxycholic acid treatment.
AB  - BACKGROUND AND AIMS: In two Japanese infants with neonatal cholestasis, 3-oxo
      Delta(4)-steroid 5beta-reductase deficiency was diagnosed based on mutations of
      the SRD5B1 gene. Unusual bile acids such as elevated 3-oxo-Delta(4) bile acids
      were detected in their serum and urine by gas chromatography-mass spectrometry.
      We studied effects of oral chenodeoxycholic acid treatment. PATIENTS AND METHODS:
      SRD5B1 gene analysis used peripheral lymphocyte genomic DNA. Diagnosis and
      treatment of these two patients were investigated retrospectively and
      prospectively investigated. RESULTS: With respect to SRD5B1, one patient was
      heterozygous (R266Q, a novel mutation) while the other was a compound
      heterozygote (G223E/R261C). Chenodeoxycholic acid treatment was effective in
      improving liver function and decreasing unusual bile acids such as 7alpha-hydroxy
      and 7alpha,12alpha-dihydroxy-3-oxo-4-cholen-24-oic acids in serum and urine.
      CONCLUSION: Primary bile acid treatment using chenodeoxycholic acid was effective
      for these patients treated in early infancy before the late stage of chronic
      cholestatic liver dysfunction.

PMID- 23160875
TI  - The IVS8-2A>G (c.913-2A>G) mutation and the PAH deficiency populations of Central
      Europe.

PMID- 23160876
TI  - Final infarct volume is a stronger predictor of outcome than recanalization in
      patients with proximal middle cerebral artery occlusion treated with endovascular
      therapy.
AB  - BACKGROUND AND PURPOSE: The rationale for recanalization therapy in acute
      ischemic stroke is to preserve brain through penumbral salvage and thus improve
      clinical outcomes. We sought to determine the relationship between
      recanalization, clinical outcomes, and final infarct volumes in acute ischemic
      stroke patients presenting with middle cerebral artery occlusion who underwent
      endovascular therapy and post-procedure magnetic resonance imaging. METHODS: We
      identified 201 patients with middle cerebral artery occlusion. Patients with
      other occlusive lesions were excluded. Baseline clinical/radiological
      characteristics, procedural outcomes (including thrombolysis in cerebral
      infarction scores), clinical outcome scores (modified Rankin scores), and final
      infarct volumes on diffusion weighted imaging were retrospectively analyzed from
      a prospectively collected database. Favorable outcome is defined as 90-day
      modified Rankin score<=2. RESULTS: Successful recanalization (thrombolysis in
      cerebral infarction grade 2b or 3) was achieved in 63.2% and favorable outcomes
      in 46% of cases. Mean infarct volume was 50.1 mL in recanalized versus 133.9 mL
      in non-recanalized patients (P<0.01) and 40.4 mL in patients with favorable
      outcomes versus 111.8 in patients with unfavorable outcomes (P<0.01). In
      multivariate analysis, thrombolysis in cerebral infarction>=2b, baseline National
      Institute of Health Stroke Scale, Alberta Stroke Program Early Computed
      Tomography scores, and age were identified as independent predictors of outcome.
      However, when infarct volumes were included in the analysis only final infarct
      volume and age remained significantly associated. CONCLUSIONS: Successful
      recanalization leads to improved functional outcomes through a reduction in final
      infarct volumes. In our series, age and final infarct volume but not
      recanalization were found to be independent predictors of outcome, supporting the
      use of final infarct volume as surrogate marker of outcome in acute stroke
      trials.

PMID- 23160877
TI  - Letter by El Husseini et al regarding article, "What causes disability after
      transient ischemic attack and minor stroke?".

PMID- 23160878
TI  - Reliability of real-time video smartphone for assessing National Institutes of
      Health Stroke Scale scores in acute stroke patients.
AB  - BACKGROUND AND PURPOSE: Telestroke reduces acute stroke care disparities between
      urban stroke centers and rural hospitals. Current technologies used to conduct
      remote patient assessments have high start-up costs, yet they cannot consistently
      establish quality timely connections. Smartphones can be used for high-quality
      video teleconferencing. They are inexpensive and ubiquitous among health care
      providers. We aimed to study the reliability of high-quality video
      teleconferencing using smartphones for conducting the National Institutes of
      Health Stroke Scale (NIHSS). METHODS: Two vascular neurologists assessed 100
      stroke patients with the NIHSS. The remote vascular neurologist assessed subjects
      using smartphone videoconferencing with the assistance of a bedside medical aide.
      The bedside vascular neurologist scored patients contemporaneously. Each vascular
      neurologist was blinded to the other's NIHSS scores. We tested the inter-method
      agreement and physician satisfaction with the device. RESULTS: We demonstrated
      high total NIHSS score correlation between the methods (r=0.949; P<0.001). The
      mean total NIHSS scores for bedside and remote assessments were 7.93+/-8.10 and
      7.28+/-7.85, with ranges, of 0 to 35 and 0 to 37, respectively. Eight categories
      had high agreement: level of consciousness (questions), level of consciousness
      (commands), visual fields, motor left and right (arm and leg), and best language.
      Six categories had moderate agreement: level of consciousness (consciousness),
      best gaze, facial palsy, sensory, dysarthria, and extinction/inattention. Ataxia
      had poor agreement. There was high physician satisfaction with the smartphone.
      CONCLUSIONS: Smartphone high-quality video teleconferencing is reliable, easy to
      use, affordable for telestroke NIHSS administration, and has high physician
      satisfaction.

PMID- 23160879
TI  - Lower susceptibility to cerebral small vessel disease in human familial
      longevity: the Leiden Longevity Study.
AB  - BACKGROUND AND PURPOSE: On MRI, cerebral white matter lesions, lacunar infarcts,
      and cerebral microbleeds are common imaging correlates of cerebral small vessel
      damage in apparently healthy elderly individuals. We investigated whether middle
      aged to elderly offspring of nonagenarian siblings, who are predisposed to become
      long-lived as well, have a lower prevalence of white matter lesions, lacunar
      infarcts, and cerebral microbleeds than control subjects. METHODS: All subjects
      were from the Leiden Longevity Study. In this study, middle-aged to elderly
      offspring of nonagenarian siblings, who are predisposed to become long-lived as
      well, were contrasted to their spouses. Cerebral small vessel disease was
      assessed using 3-T MRI. RESULTS: Offspring were less likely to have severe
      periventricular frontal caps (odds ratio [OR], 0.3; 95% confidence interval [CI],
      0.1-1.1; P trend=0.01) and severe periventricular bands (OR, 0.4; 95% CI, 0.2
      0.8; P trend=0.02). Moreover, offspring were less likely to have frontal (OR,
      0.4; 95% CI, 0.2-0.9; P trend=0.05), parietal (OR, 0.4; 95% CI, 0.1-0.9; P
      trend=0.001), temporal (OR, 0.3; 95% CI, 0.1-0.8]; P trend=0.004), and occipital
      subcortical white matter lesions (OR, 0.3; 95% CI, 0.1-0.6; P trend=0.001).
      Prevalence of lacunar infarcts also was lower in offspring (OR, 0.3; 95% CI, 0.1
      1.1; P=0.07). Prevalence of microbleeds was not significantly different in
      offspring and control subjects. CONCLUSIONS: Exceptional familial longevity is
      associated with a lower susceptibility to white matter lesions and lacunar
      infarcts, but not cerebral microbleeds.

PMID- 23160881
TI  - Letter by Simone Vidale regarding article,"Relation between change in blood
      pressure in acute stroke and risk of early adverse events and poor outcome".

PMID- 23160880
TI  - Impact of ACE2 deficiency and oxidative stress on cerebrovascular function with
      aging.
AB  - BACKGROUND AND PURPOSE: Angiotensin II produces oxidative stress and endothelial
      dysfunction in cerebral arteries, and angiotensin II type I receptors may play a
      role in longevity and vascular aging. Angiotensin-converting enzyme type 2 (ACE2)
      converts angiotensin II to angiotensin (1-7) and thus, may protect against
      effects of angiotensin II. We hypothesized that ACE2 deficiency increases
      oxidative stress and endothelial dysfunction in cerebral arteries and examined
      the role of ACE2 in age-related cerebrovascular dysfunction. METHODS: Endothelial
      function, expression of angiotensin system components, NADPH oxidase subunits,
      and proinflammatory cytokines were examined in cerebral arteries from adult (12
      months old) and old (24 months old) ACE2 knockout (KO) and wild-type (WT) mice.
      The superoxide scavenger tempol was used to examine the role of oxidative stress
      on endothelial function. RESULTS: Vasodilatation to acetylcholine was impaired in
      adult ACE2 KO (24+/-6% [mean+/-SE]) compared with WT mice (52+/-7%; P<0.05). In
      old mice, vasodilatation to acetylcholine was impaired in WT mice (29+/-6%) and
      severely impaired in ACE2 KO mice (7+/-5%). Tempol improved endothelial function
      in adult and old ACE2 KO and WT mice. Aging increased mRNA for tumor necrosis
      factor-alpha in WT mice, and significantly increased mRNA levels of NAPDH oxidase
      2, p47(phox), and Regulator of calcineurin 1 in both ACE2 KO and WT mice. mRNA
      levels of angiotensin system components did not change during aging. CONCLUSIONS:
      ACE2 deficiency impaired endothelial function in cerebral arteries from adult
      mice and augmented endothelial dysfunction during aging. Oxidative stress plays a
      critical role in cerebrovascular dysfunction induced by ACE2 deficiency and
      aging.

PMID- 23160882
TI  - Risk of intracranial hemorrhage with protease-activated receptor-1 antagonists.
AB  - BACKGROUND AND PURPOSE: Recent clinical trial data suggest that protease
      activated receptor-1 (PAR-1) antagonists may increase the risk of intracranial
      hemorrhage. Our objective was to investigate the qualitative and quantitative
      risks of intracranial hemorrhage in patients receiving PAR-1 antagonist therapy.
      METHODS: Pubmed, EMBASE, Cochrane Central Register of Controlled Trials, and
      Clinicaltrials.gov from 1966 to May 2012, were searched to identify relevant
      studies. We included randomized controlled trials that included a comparison of
      PAR-1 antagonist with placebo and in which the total number of patients and
      intracranial hemorrhage events were reported separately for active treatment and
      control groups. Summary incidence rates, relative risks, and 95% confidence
      intervals (CIs) were calculated using random-effects models. Between-study
      heterogeneity was assessed using the I2 statistic. RESULTS: In 9 PAR-1 antagonist
      trials with 42000 patients with a history of thrombotic vascular disease or acute
      coronary syndrome, PAR-1 antagonist treatment was associated with increased risk
      of intracranial hemorrhage (0.59% vs 0.30%; relative risk, 1.98; 95% CI, 1.46
      2.68; P<0.00001; number needed to harm, 345). There was no heterogeneity across
      trials (P=0.84; I2=0%), PAR-1 antagonist agent (P=0.52), treatment duration
      (P=0.38), or trial-qualifying event (P=0.59). Risk of death from any cause or a
      cardiovascular cause did not differ between active treatment and control groups.
      CONCLUSIONS: In a pooled analysis of data from 9 trials, PAR-1 antagonist therapy
      was associated with an increased risk for intracranial hemorrhage.

PMID- 23160883
TI  - Letter by Saji and Kimura regarding article, "Arterial stiffness and cerebral
      small vessel disease: the Rotterdam scan study".

PMID- 23160884
TI  - A population-based study of hospital care costs during 5 years after transient
      ischemic attack and stroke.
AB  - BACKGROUND AND PURPOSE: Few studies have evaluated long-term costs after stroke
      onset, with almost no cost data for transient ischemic attack (TIA). We studied
      hospital costs during the 5 years after TIA or stroke in a population-based
      study. METHODS: Patients from a United Kingdom population-based cohort study
      (Oxford Vascular Study) were recruited from 2002 to 2007. Analysis was based on
      follow-up until 2010. Hospital resource usage was obtained from patient hospital
      records and valued using 2008/2009 unit costs. Because not all patients had full
      5-year follow-up, we used nonparametric censoring techniques. RESULTS: Among 485
      TIA and 729 stroke patients ascertained and included, mean censor-adjusted 5-year
      hospital costs after index stroke were $25,741 (95% confidence interval, 23,659
      27,914), with costs varying considerably by severity: $21,134 after minor stroke;
      $33,119 after moderate stroke; and $28,552 after severe stroke. For the 239
      surviving stroke patients who had reached final follow-up, mean costs were
      $24,383 (95% confidence interval, 20,156-28,595), with more than half of costs
      ($12,972) being incurred in the first year after the event. After index TIA, the
      mean censor-adjusted 5-year costs were $18,091 (95% confidence interval, 15,947
      20,258). A multivariate analysis showed that event severity, recurrent stroke,
      and coronary events after the index event were independent predictors of 5-year
      costs. Differences by stroke subtype were mostly explained by stroke severity and
      subsequent events. CONCLUSIONS: Long-term hospital costs after TIA and stroke are
      considerable, but they are mainly incurred during the first year after the index
      event. Event severity and experiencing subsequent stroke and coronary events
      after the index event accounted for much of the increase in costs.

PMID- 23160885
TI  - Risk factors and stroke mechanisms in atherosclerotic stroke: intracranial
      compared with extracranial and anterior compared with posterior circulation
      disease.
AB  - BACKGROUND AND PURPOSE: The aim of this study was to investigate differences in
      risk factors and stroke mechanisms between intracranial atherosclerosis (ICAS)
      and extracranial atherosclerosis (ECAS) and between anterior and posterior
      circulation atherosclerosis. METHODS: A multicenter, prospective, Web-based
      registry was performed on atherosclerotic strokes using diffusionweighted
      magnetic resonance imaging and magnetic resonance angiography. Stroke mechanisms
      were categorized as artery-to-artery embolism, in situ thrombo-occlusion, local
      branch occlusion, or hemodynamic impairment. RESULTS: Onethousand patients were
      enrolled from 9 university hospitals. Age (odds ratio [OR], 1.033; 95% confidence
      interval [CI], 1.018-1.049), male gender (OR, 3.399; 95% CI, 2.335-4.949), and
      hyperlipidemia (OR, 1.502; 95% CI, 1.117-2.018) were factors favoring ECAS (vs
      ICAS), whereas hypertension (OR, 1.826; 95% CI, 1.274-2.618; P=0.001) and
      diabetes mellitus (OR, 1.490; 95% CI, 1.105-2.010; P=0.009) were related to
      posterior (vs anterior) circulation diseases. Metabolic syndrome was a factor
      related to ICAS (vs ECAS) only in posterior circulation strokes (OR, 2.433; 95%
      CI, 1.005-5.890; P=0.007). Stroke mechanisms included arterytoartery embolism
      (59.7%), local branch occlusion (14.9%), in situ thrombo-occlusion (13.7%),
      hemodynamic impairment (0.9%), and mixed (10.8%). Anterior ICAS was more often
      associated with artery-to-artery embolism (51.8% vs 34.0%) and less often
      associated with local branch occlusion (12.3% vs 40.4%) than posterior ICAS
      (P<0.001). CONCLUSIONS: The prevalence of risk factors and stroke mechanisms
      differ between ICAS and ECAS, and between anterior and posterior circulation
      atherosclerosis. Posterior ICAS seems to be closely associated with metabolic
      derangement and local branch occlusion. Prevention and management strategies may
      have to consider these differences.

PMID- 23160886
TI  - Risk of intracranial hemorrhage with protease-activated receptor-1 antagonists.

PMID- 23160887
TI  - Trends in substance abuse preceding stroke among young adults: a population-based
      study.
AB  - BACKGROUND AND PURPOSE: Approximately 5% of strokes occur in adults aged 18 to 44
      years. Substance abuse is a prevalent risk factor for stroke in young adults. We
      sought to identify trends in substance abuse detection among stroke patients.
      METHODS: Using a population-based design, we sought to identify all patients aged
      18 to 54 years experiencing a stroke (ischemic or hemorrhagic) in the Greater
      Cincinnati and Northern Kentucky Study region during 1993 to 1994, 1999, and
      2005. Demographic and clinical characteristics and substance use data were
      obtained retrospectively from chart review and adjudicated by physicians.
      RESULTS: The number of young patients identified with a stroke increased from
      1993 to 1994 (297) to 2005 (501). Blacks (61% vs 51%; P<0.02) and men (61% vs
      47%; P<0.002) reported substance abuse (current smoking, alcohol, or illegal drug
      use) more frequently than did whites and women. Overall use of substances
      increased across study periods, 45% in 1993 versus 62% in 2005 (P=0.003). The
      trend was significant for illegal drug use (3.8% in 1993 vs 19.8% in 2005) and
      ever smoking (49% in 1993 vs 66% in 2005). Documentation of both cocaine and
      marijuana use increased over time. In 2005, half of young adults with a stroke
      were current smokers, and 1 in 5 abused illegal drugs. CONCLUSIONS: Substance
      abuse is common in young adults experiencing a stroke. The observed increase in
      substance abuse is contributing to the increased incidence of stroke in young
      adults. Patients aged younger than 55 years who experience a stroke should be
      routinely screened and counseled regarding substance abuse.

PMID- 23160888
TI  - Face selective reduction of the exocyclic double bond in isatin derived
      spirocyclic lactones.
AB  - We report an unusual face selective reduction of the exocyclic double bond in the
      alpha-methylene-gamma-butyrolactone motif of spiro-oxindole systems. The spiro
      oxindoles were assembled by an indium metal mediated Barbier-type reaction
      followed by an acid catalyzed lactonization.

PMID- 23160889
TI  - Molecular cloning and characterization of Schistosoma japonicum aldose reductase.
AB  - Antioxidant defense is an essential mechanism for schistosomes to cope with
      damage from host immune-generated reactive oxygen species. The evaluation of the
      effects of aldose reductase, an important enzyme that may be involved in this
      system, has long been neglected. In the present study, aldose reductase of
      Schistosoma japonicum (SjAR) was cloned and characterized. The activity of SjAR
      was assessed in vitro and was suppressed by the reported inhibitor, epalrestat.
      RT-PCR analysis revealed that SjAR was expressed at each of the development
      stages analyzed with increased levels in cercariae. The results also showed that
      SjAR was expressed at higher levels in adult male worms than in adult female
      worms. Indirect enzyme-linked immunosorbent assay and western blot analysis
      indicated that the purified recombinant SjAR (rSjAR) protein displayed a
      significant level of antigenicity. Immunolocalization analysis revealed that SjAR
      was mainly distributed in the gynecophoral canal of adult male worms. BALB/c mice
      immunized with rSjAR induced a 32.91 % worm reduction compared to the adjuvant
      group (P < 0.01). Moreover, a 28.27 % reduction in egg development in the liver
      (P > 0.05) and a 42.75 % reduction in egg development in the fecal samples (P <
      0.05) were also observed. These results suggested that SjAR may be a potential
      new drug target or vaccine candidate for schistosomes.

PMID- 23160890
TI  - Comparative study of nitric oxide (NO) production during human hydatidosis:
      relationship with cystic fluid fertility.
AB  - Human hydatidosis is characterized by a prolonged coexistence of Echinococcus
      granulosus and its host without effective rejection of the parasite. This
      parasitic infection constitutes a major health problem in Algeria. In this study,
      we investigated in vivo production of nitrite (NO(2)(-) + NO(3)(-)) in sera of
      Algerian patients carrying different cyst locations. Nitrite (NO(2)(-) + NO(3)(
      )) levels were evaluated by the Griess method. Our results indicated that the
      levels of nitrite were significantly higher in the sera of hydatic patients than
      those of healthy controls supporting the involvement of nitric oxide (NO) in
      antihydatic action. The levels of nitrite in sera of the patients with hepatic
      hydatidosis were significantly higher than those with pulmonary infection. The
      lower serum (NO(2)(-) + NO(3)(-)) levels were observed in the relapsing cases. In
      addition, (NO(2)(-) + NO(3)(-)) levels of fertile hydatic fluids were
      significantly higher compared to infertile fluids. Our results suggest that the
      presence of NO products in hydatic fluids seems to be related to the location and
      the fertility of hydatic cysts. The assessment of protein concentration in
      hydatic fluids showed that the concentration of proteins was not exclusively
      dependent on the fertility but on the cyst locations. The assessment of (NO(2)(-)
      + NO(3)(-)) production in hydatic patients may be a useful tool to evaluate
      effector mechanisms of NO and clinical manifestations.

PMID- 23160891
TI  - Trypanosoma cruzi experimental congenital transmission associated with TcV and
      TcI subpatent maternal parasitemia.
AB  - The congenital transmission of Chagas disease is associated with an increase in
      parasitemia during pregnancy, maternal and fetal immunity, and populations of
      Trypanosoma cruzi. In this study, the biological behavior of TcI and TcV
      (isolated from a human congenital case) strains and their potential for
      experimental congenital transmission were evaluated in female BALB/C mice.
      Parasitemia was estimated by fresh blood examination, semiquantitative
      microhematocrit, and hemoculture, while congenital transmission was evaluated by
      culture in the liver infusion tryptose medium and by polymerase chain reaction
      (PCR) of the pups' tissues on postnatal day 7 and of the pups' blood sample at 30
      days after birth. Infection was detected in 100 % of the females. Both strains
      showed subpatent parasitemia, which was higher for TcV infection. The presence of
      amastigote nest was detected only in an animal infected with TcI. The
      inflammatory process was more frequent (p = 0.001) in the tissues of the animals
      infected with TcV (58.6 %) than TcI (31.1 %). The fertility rates of females
      mated after 35 days postinfection were similar (90 % for TcV, 88.9 % for TcI; p =
      0.938). Parasitemia did not change during pregnancy. The average number of
      pups/female was greater (p = 0.03) in mice with TcV infection (8.30) than in
      those with TcI infection (4.78). Congenital transmission was detected exclusively
      by PCR in 50.9 % of the pups, 46.6 % for TcV and 58.1 % for TcI. The PCR
      positivity for TcI was higher in the blood than in the tissue (p = 0.003). These
      results demonstrate the T. cruzi experimental congenital infection associated
      with subpatent maternal parasitemia of TcI and TcV.

PMID- 23160892
TI  - Genetic characterization of Toxoplasma gondii in wildlife from Alabama, USA.
AB  - The genetic diversity of Toxoplasma gondii circulating in wildlife is of interest
      to understand the transmission of this parasite in the environment. In the
      present study, we genetically characterized five T. gondii isolates from
      different wild animals including two isolates from a bobcat (Lynx rufus), one
      from a red-shouldered hawk (Buteo lineatus), one from a white-tailed deer
      (Odocoileus virginianus), and one from a bald eagle (Haliaeetus leucocephalus).
      Genotyping of these samples using 11 PCR-restriction fragment length polymorphism
      markers (SAG1, 5'- and 3'-SAG2, alt.SAG2, SAG3, BTUB, GRA6, c22-8, c29-2, L358,
      PK1, and Apico) revealed two types, including type I (ToxoDB#10) and type 12
      (ToxoDB#5). This is the first report of genetic characterization of T. gondii
      strains in wildlife from Alabama and from a red-shouldered hawk.

PMID- 23160893
TI  - Chemical constituents and larvicidal potential of Feronia limonia leaf essential
      oil against Anopheles stephensi, Aedes aegypti and Culex quinquefasciatus.
AB  - In the present investigation, the leaf essential oil of Feronia limonia was
      evaluated for chemical constituents and mosquito larvicidal activity against the
      larvae of Anopheles stephensi, Aedes aegypti and Culex quinquefasciatus. GC and
      GC-MS analyses revealed that the essential oil contain 51 compounds. Estragole
      (34.69 %) and beta-pinene(23.59 %) were identified as the major constituents
      followed by methyl (Z)-caryophyllene (11.05 %), eugenol (6.50 %), linalool (3.97
      %), phytol (3.27 %), sabinene (2.41 %) and limonene (2.27 %). Larval mortality
      was observed after 12 and 24 h of exposure period. The oil showed remarkable
      larvicidal activity against A. stephensi (LC(50) = 38.93 and LC(90) = 108.64 ppm
      (after 12 h); LC(50) = 15.03 and LC(90) = 36.69 ppm (after 24 h)), A. aegypti
      (LC(50) = 37.60 and LC(90) = 104.69 ppm (after 12 h); LC(50) = 11.59 and LC(90) =
      42.95 ppm (after 24 h)) and C. quinquefasciatus (LC(50) = 52.08 and LC(90) =
      124.33 ppm (after 12 h); LC(50) = 22.49 and LC(90) = 60.90 ppm (after 24 h)).
      Based on the results, the essential oil of F. limonia can be considered as a new
      source of larvicide for the control of vector mosquitoes.

PMID- 23160895
TI  - The destructive effects of high-intensity focused ultrasound on hydatid cysts
      enhanced by ultrasound contrast agent and superabsorbent polymer alone or in
      combination.
AB  - Cystic echinococcosis, caused by the metacestode stage of Echincoccus granulosus,
      remains endemic in many regions around the world. The present work evaluated
      whether or not a superabsorbent polymer (SAP) and ultrasound contrast agent (UCA)
      alone or in combination could enhance damage efficacy of high-intensity focused
      ultrasound (HIFU) on hydatid cysts in vitro. HIFU of 100 W acoustic power, with
      the aid of 0.1 ml UCA and 0.1 g SAP alone or in combination, was used to ablate
      hydatid cysts in vitro. The comparison of ultrasound image for each layer of
      hydatid cyst before and after HIFU ablation was made immediately, and the
      protoscolices of the cysts were stained by eosin exclusion assay, and the
      structures of protoscolices were observed by light microscopy. To understand the
      destructive effects of HIFU, the pathological changes in cyst walls of hydatid
      cyst ablated with HIFU were examined. The results demonstrated that HIFU had some
      lethal effect on hydatid cysts: echo enhancement of ultrasound image, increase of
      mortality rate of protoscolices, serious structural damage of protoscolices, and
      complete destruction or even disappearance of laminated layer and germinal layer
      was observed in the group of HIFU combined with UCA and SAP alone or in
      combination. It was found that the destructive effect of HIFU aided with a
      combination of UCA and SAP to hydatid cysts was more effective than that of HIFU
      just aided with UCA or SAP alone. These results suggested that UCA and SAP might
      be used as a HIFU enhancing agent to improve the efficacy of HIFU ablation to
      hydatid cysts, which could be a possible therapeutic option for cystic
      echinococcosis.

PMID- 23160894
TI  - Experimental infections with the protozoan parasite Histomonas meleagridis: a
      review.
AB  - In recent years, a number of studies about Histomonas meleagridis, and more
      specifically about experiments in vivo involving H. meleagridis to investigate
      the pathogenicity and efficacy of drugs or vaccines, have been published.
      Together with older publications, a considerable amount of information about
      experimental infections with H. meleagridis exist, which is helpful for planning
      future animal studies and can reduce the number of birds used in such studies
      toward better animal welfare. One hundred sixty-seven publications describing
      experimental infections with H. meleagridis were published in scientific journals
      between 1920 and 2012. One hundred forty-two of these publications describe
      infections of turkeys (Meleagris gallopavo) and 52 infections of chickens (Gallus
      gallus). In 18 studies, experiments involving other species were done. The most
      popular routes of infection were the intracloacal application of histomonal
      trophozoites from culture material, from lesions or from feces of infected birds,
      or using larvae of the cecal worm Heterakis gallinarum (83 studies) and the oral
      application of eggs or other stages of the cecal worm containing histomonal
      stages (83 studies). During the last 10 years, intracloacal application of
      trophozoites has become the most popular way to experimentally infect birds with
      H. meleagridis due to its high reproducibility and reliability. In most studies,
      infection doses of several 10,000 or 100,000 histomonal trophozoites were used
      for infection, and the resulting mortality in turkeys was more than 70 %. First
      mortality can occur as early as 6 days p.i.; peak mortality usually is 13-15 days
      p.i. Lower infection doses may delay mortality about 2 days. In chickens infected
      by the intracloacal route, mortality and clinical signs are rare, but infection
      rates are similar. Cecal lesions can be observed from 3 to 4 days p.i., lesions
      up to 3 weeks p.i.; liver lesions may be lacking completely or be present only in
      a small number of birds. In most studies infecting birds with Heterakis eggs
      containing histomonal stages, several 100 to 1,000 Heterakis eggs were used.
      However, lower doses might be sufficient, as infection with as few as 58 eggs per
      bird caused a mortality up to 90 % in turkeys. Clinical symptoms start 9 days
      p.i., and first mortality occurs after 12 days, while most of the infected birds
      die between 19 and 21 days p.i. The infectivity of Heterakis eggs containing
      histomonal stages for chickens is similar as for turkeys, but mortality and
      clinical signs are rare. Further infection was done by oral application of
      histomonal trophozoites either grown in culture or using lesions or feces of
      infected birds (26 studies). These yielded very mixed results, with infection
      rates between 0 and more than 80 % in turkeys and chickens. After successful oral
      infection of turkeys, mortality occurs at roughly the same time as after
      intracloacal infection. Further 18 studies employed seeder birds to infect in
      contact birds. Other means of infection were exposure to contaminated soil or
      litter (22 studies), feeding contaminated earthworms (7 studies), intracecal
      inoculation (4 studies), or parenteral injection (4 studies). Main methods to
      assess the course of the infection were mortality, observation of clinical signs
      and pathological lesions, monitoring of the weight of the infected birds, and
      detection of the parasite by various methods.

PMID- 23160896
TI  - Optic disc detection in color fundus images using ant colony optimization.
AB  - Diabetic retinopathy has been revealed as the most common cause of blindness
      among people of working age in developed countries. However, loss of vision could
      be prevented by an early detection of the disease and, therefore, by a regular
      screening program to detect retinopathy. Due to its characteristics, the digital
      color fundus photographs have been the easiest way to analyze the eye fundus. An
      important prerequisite for automation is the segmentation of the main anatomical
      features in the image, particularly the optic disc. Currently, there are many
      works reported in the literature with the purpose of detecting and segmenting
      this anatomical structure. Though, none of them performs as needed, especially
      when dealing with images presenting pathologies and a great variability. Ant
      colony optimization (ACO) is an optimization algorithm inspired by the foraging
      behavior of some ant species that has been applied in image processing with
      different purposes. In this paper, this algorithm preceded by anisotropic
      diffusion is used for optic disc detection in color fundus images. Experimental
      results demonstrate the good performance of the proposed approach as the optic
      disc was detected in most of all the images used, even in the images with great
      variability.

PMID- 23160897
TI  - Probabilistic neural network approach for the detection of SAHS from overnight
      pulse oximetry.
AB  - Diagnosis of sleep apnea hypopnoea syndrome (SAHS) depends on the apnea-hypopnea
      index determined by the standard in-laboratory overnight polysomnography (PSG).
      PSG is a costly, labor intensive and, at times, inaccessible approach. Because of
      the high demand, the need for timely diagnosis and the associated costs, novel
      methods for SAHS detection are required. In this study, a novel multivariate
      system is proposed for SAHS detection from the analysis of overnight blood oxygen
      saturation (SpO2). 115 subjects with SAHS suspicion were studied. A starting set
      of 17 time domain, stochastic, frequency-domain and nonlinear features were
      initially computed from SpO2 recordings. Sequential forward feature selection and
      a probabilistic neural network with leave-one-out cross-validation were applied.
      Oxygen desaturations below a 4 % threshold within 30 s (ODI430), restorations of
      4 % within 10 s (RES4), median value (Sat50), SD1 Poincare descriptor and the
      relative power in the 0.013-0.067 Hz frequency band (PSD15/75) formed the optimum
      features subset. 92.4 % sensitivity and 95.9 % specificity were achieved. Results
      significantly outperformed the univariate and multivariate approaches reported in
      literature. The outcome is a simple cost-effective tool that could be used as an
      alternative or supplementary method in a domiciliary approach to early diagnosis
      of SAHS.

PMID- 23160898
TI  - Quantitative assessment of the association between miR-196a2 rs11614913
      polymorphism and gastrointestinal cancer risk.
AB  - Published data on the association between miR-196a2 rs11614913 polymorphism and
      risk of gastrointestinal (GI) cancers are inconsistent among studies. To clarify
      the association, we performed a comprehensive literature search and a meta
      analysis. We searched multiple databases to identify genetic association studies
      investigating the effect of miR-196a2 rs11614913 polymorphism on GI cancers with
      the last report up to January 18, 2012. The odds ratio (OR) and its 95 %
      confidence interval (95 % CI) were calculated to assess the strength of
      association. A total of 13 studies including 4,947 cases and 5,642 controls based
      on the search criteria were involved in this meta-analysis. In the overall
      analysis, it was suggested that variant C allele of miR-196a2 rs11614913
      polymorphism could significantly increase risk of GI cancers in different genetic
      models (C vs T: OR = 1.17, 95 % CI = 1.07-1.28, P = 0.0008; CT + CC vs TT: OR =
      1.26, 95 % CI = 1.08-1.48, P = 0.004; CC vs CT + TT: OR = 1.23, 95 % CI = 1.08
      1.39, P = 0.002; CC vs TT: OR = 1.55, 95 % CI = 1.24-1.94, P = 0.0001; CT vs TT:
      OR = 1.20, 95 % CI = 1.02-1.40, P = 0.03). When stratified by ethnicity, we found
      a significant association in Asian population, as well as Caucasian population.
      When stratified by cancer types, we found a significant association in colorectal
      cancer, as well as esophageal cancer. We did not find a significant association
      between miR-196a2 rs11614913 polymorphism and hepatocellular carcinoma risk. For
      gastric cancer, a significantly increased cancer risk was observed only in
      homozygote comparison. This meta-analysis demonstrates that miR-196a2 rs11614913
      polymorphism is significantly associated with risk of GI cancers.

PMID- 23160899
TI  - Interfering growth of malignant melanoma with Ang2-siRNA.
AB  - To investigate the intervention therapy effect on the growth of malignant
      melanoma, we have made an observation of expression levels of Ang2 in malignant
      melanoma cells, which was transduced by small interfering RNA (Ang2-siRNA) of
      Ang2 in vitro and in vivo. We successfully constructed Ang2-siRNA lent virus, and
      constructed nude mice model by transplanting malignant melanoma. Ang2-siRNA lent
      virus inhibited Ang2 mRNA of malignant melanoma in vitro and in vivo, and
      inhibited malignant melanoma tumor growth at the same time. Ang2-siRNA lent virus
      can interfere expression levels of Ang2 in malignant melanoma cells, inhibit
      tumor growth, and silent Ang2 gene expression, which may pave a new way for
      clinical gene therapy of malignant melanoma.

PMID- 23160900
TI  - Antisense-overexpression of the MsCOMT gene induces changes in lignin and total
      phenol contents in transgenic tobacco plants.
AB  - Initially, we isolated the caffeic acid O-methyltransferase (COMT) gene from
      Miscanthus sinensis (accession number HM062766.1). Next, we produced transgenic
      tobacco plants with down-regulated COMT gene expression to study its control of
      total phenol and lignin content and to perform morphological analysis. These
      transgenic plants were found to have reduced PAL and ascorbate peroxidases
      expression, which are related to the phenylpropanoid pathway and antioxidant
      activity. The MsCOMT-down-regulated plants had decreased total lignin in the
      leaves and stem compared with control plants. Reduced flavonol concentrations
      were confirmed in MsCOMT-down-regulated transgenic plants. We also observed a
      morphological difference, with reduced plant cell number in transgenic plants
      harboring antisense MsCOMT. The transgenic tobacco plants with down-regulated
      COMT gene expression demonstrate that COMT plays a crucial role related to
      controlling lignin and phenol content in plants. Also, COMT activity may be
      related to flavonoid production in the plant lignin pathway.

PMID- 23160901
TI  - Increased activation of NADPH oxidase 4 in the pulmonary vasculature in
      experimental diaphragmatic hernia.
AB  - AIM: Persistent pulmonary hypertension remains a major cause of mortality and
      morbidity in congenital diaphragmatic hernia (CDH). NADPH oxidases (Nox) are the
      main source of superoxide production in vasculature. Nox4 is highly expressed in
      the smooth muscle and endothelial cells of the vascular wall and increased
      activity has been reported in the pulmonary vasculature of both experimental and
      human pulmonary hypertension. Peroxisome proliferator-activated receptor
      (PPARgamma) is a key regulator of Nox4 expression. Targeted depletion of
      PPARgamma results in pulmonary hypertension phenotype whereas activation of
      PPARgamma attenuates pulmonary hypertension and reduces Nox4 production. The
      nitrofen-induced CDH model is an established model to study the pathogenesis of
      pulmonary hypertension in CDH. It has been previously reported that PPARgamma
      signaling is disrupted during late gestation and H(2)O(2) production is increased
      in nitrofen-induced CDH. We designed this study to investigate the hypothesis
      that Nox4 expression and activation is increased and vascular PPARgamma is
      decreased in nitrofen-induced CDH. METHODS: Pregnant rats were treated with
      either nitrofen or vehicle on gestational day 9 (D9). Fetuses were sacrificed on
      D21 and divided into control and CDH. RT-PCR, western blotting and confocal
      immunofluorescence-double-staining were performed to determine pulmonary
      expression levels of PPARgamma, Nox4 and Nox4-activation (p22(phox)). RESULTS:
      There was a marked increase in medial and adventitial thickness in pulmonary
      arteries of all sizes in CDH compared to controls. Pulmonary Nox4 levels were
      significantly increased whereas PPARgamma levels were decreased in nitrofen
      induced CDH compared to controls. Western blotting revealed increased pulmonary
      protein expression of the Nox4-activating subunit p22(phox) and decreased protein
      expression of PPARgamma in CDH compared to controls. Confocal-microscopy
      confirmed markedly increased pulmonary expression of the Nox4 activating subunit
      p22(phox) accompanied by decreased perivascular PPARgamma expression in lungs of
      nitrofen-exposed fetuses compared to controls. CONCLUSION: To our knowledge, the
      present study is the first to report increased Nox4 production in the pulmonary
      vasculature of nitrofen-induced CDH. Down-regulation of the PPARgamma-signaling
      pathway may lead to increased superoxide production, resulting in pulmonary
      vascular dysfunction and contributing to pulmonary hypertension in the nitrofen
      induced CDH model. PPARgamma-activation inhibiting Nox4 production may therefore
      represent a potential therapeutic approach for the treatment of pulmonary
      hypertension in CDH.

PMID- 23160902
TI  - Apelin is a marker of the progression of liver fibrosis and portal hypertension
      in patients with biliary atresia.
AB  - PURPOSE: Apelin, the endogenous ligand of the angiotensin-like-receptor 1 (APJ),
      is thought to play an important role in liver disease. This study investigated
      the apelin expression in different stages of biliary atresia (BA) and
      investigated whether it is associated with the progression of disease. METHODS:
      Liver tissues were obtained from patients at Kasai's procedure (KP), the follow
      up stage after KP (Post-KP) and at liver transplantation (LT).
      Immunohistochemistry for apelin and its receptor APJ and real-time quantitative
      reverse transcriptase polymerase chain reaction for apelin mRNA expression were
      conducted. RESULTS: The immunohistochemical study revealed that apelin was mainly
      localized in the perivenular areas of control liver tissue, and slightly detected
      in the hepatic stellate cells (HSC) and hepatocytes, whereas intense apelin
      immunoreactivity was detected in perivenular areas, HSC and hepatocytes of LT
      liver tissue. The apelin mRNA expression level was significantly higher in the LT
      group than in the KP and Post-KP group. Significant linear correlations were
      observed between the apelin mRNA level and liver fibrosis, serum total bilirubin
      and the grade of esophageal varices. CONCLUSIONS: The hepatic apelin-APJ system
      is markedly activated in the progression of BA, especially in end-stage
      cirrhosis. The apelin expression level accurately reflects the severity of
      hepatic fibrosis and esophageal varices and therefore could be used as a
      prognostic factor in BA patients.

PMID- 23160903
TI  - Bowel re-dilation following serial transverse enteroplasty (STEP).
AB  - PURPOSE: The serial transverse enteroplasty (STEP) operation tapers and lengthens
      dilated small bowel. Some patients demonstrate bowel re-dilation following STEP.
      Factors associated with bowel re-dilation and its effect upon clinical outcome
      were evaluated. METHODS: Twenty STEP operations were reviewed. Sixteen cases were
      operated for failure to advance enteral feeding and were further analyzed.
      Available pre- and post-STEP radiographs were independently assessed for bowel re
      dilation by two experienced pediatric radiologists. Potential factors of re
      dilation were evaluated. Full enteral autonomy was defined as no longer requiring
      parenteral nutrition (PN) and remaining off PN for at least 12 months after STEP.
      RESULTS: There was complete concordance between the radiologists. 9 of 16
      patients demonstrated radiographic bowel re-dilation following STEP. Age, follow
      up duration, time interval between STEP and last imaging reviewed, gender,
      diagnoses, pre- and post-STEP bowel length and width were not significantly
      associated with re-dilation. However, median post-STEP duration of PN was
      significantly longer in the re-dilated group than in the non-dilated group (41
      vs. 3 months, p = 0.006). In addition, only 1 of 9 re-dilated patients achieved
      enteral autonomy as compared with 6 of 7 non-dilated patients (p = 0.009).
      CONCLUSION: Longer PN duration after STEP increases probability of bowel re
      dilation. Patients who re-dilated following STEP are significantly less likely to
      achieve enteral autonomy. Larger prospective data collections are warranted to
      further explore these relationships.

PMID- 23160904
TI  - Our response to Letter.

PMID- 23160905
TI  - Indian drug maker cuts price of three cancer drugs by between 50% and 63%.

PMID- 23160906
TI  - Relatives of people who die from sudden cardiac death are at increased risk of
      CVD.

PMID- 23160907
TI  - Fasting makes little difference to results of lipid tests.

PMID- 23160908
TI  - Pictorial health warnings on cigarette packs have more impact on smokers than
      words, US study shows.

PMID- 23160909
TI  - Different methylation and microRNA expression pattern in male and female familial
      breast cancer.
AB  - Epigenetic regulation, has been very scarcely explored in familial breast cancer
      (BC). In the present study RASSF1A and RAR beta promoter methylation and miR17,
      miR21, miR 124, and let-7a expression were investigated to highlight possible
      differences of epigenetic regulation between male and female familial BC, also in
      comparison with sporadic BC. These epigenetic alterations were studied in 56
      familial BC patients (27 males and 29 females) and in 16 female sporadic cases.
      RASSF1A resulted more frequently methylated in men than women (76% vs. 28%,
      respectively, P = 0.0001), while miR17 and let-7a expression frequency was higher
      in women than in men (miR17: 66% in women vs. 41% in men, P < 0.05; let-7a: 45%
      in women vs. 15% in men, P = 0.015). RASSF1A methylation affected 27.6% of
      familial BC while 83% of familial cases showed high expression of the gene (P =
      0.025); on the contrary, only 17% of familial BC presented RAR beta methylation
      and 55% of familial cases overexpressed this gene (P = 0.005). Moreover, miR17,
      miR21, and let-7a resulted significantly overexpressed in familial compared to
      sporadic BC. RASSF1A overexpression (86% vs. 65%, P = 0.13) and RAR beta
      overexpression (57% vs. 32%, P = 0.11) were higher in BRCA1/2 carriers even if
      not statistical significance was reached. BRCA mutation carriers also
      demonstrated significant overexpression of: miR17 (93% vs. 35%, P = 0.0001), let
      7a (64% vs. 16%, P = 0.002), and of miR21 (100% vs. 65%, P = 0.008). In
      conclusion, the present data suggest the involvement of RASSF1A in familial male
      BC, while miR17 and let-7a seem to be implied in familial female BC.

PMID- 23160910
TI  - Coupling between resting cerebral perfusion and EEG.
AB  - While several studies have investigated interactions between the
      electroencephalography (EEG) and functional magnetic resonance imaging BOLD
      signal fluctuations, less is known about the associations between EEG
      oscillations and baseline brain haemodynamics, and few studies have examined the
      link between EEG power outside the alpha band and baseline perfusion. Here we
      compare whole-brain arterial spin labelling perfusion MRI and EEG in a group of
      healthy adults (n = 16, ten females, median age: 27 years, range 21-48) during an
      eyes closed rest condition. Correlations emerged between perfusion and global
      average EEG power in low (delta: 2-4 Hz and theta: 4-7 Hz), middle (alpha: 8-13
      Hz), and high (beta: 13-30 Hz and gamma: 30-45 Hz) frequency bands in both
      cortical and sub-cortical regions. The correlations were predominately positive
      in middle and high-frequency bands, and negative in delta. In addition, central
      alpha frequency positively correlated with perfusion in a network of brain
      regions associated with the modulation of attention and preparedness for external
      input, and central theta frequency correlated negatively with a widespread
      network of cortical regions. These results indicate that the coupling between
      average EEG power/frequency and local cerebral blood flow varies in a frequency
      specific manner. Our results are consistent with longstanding concepts that
      decreasing EEG frequencies which in general map onto decreasing levels of
      activation.

PMID- 23160911
TI  - Fluoride and calcium-phosphate coated sponges of the magnesium alloy AX30 as bone
      grafts: a comparative study in rabbits.
AB  - Biocompatibility and degradation of magnesium sponges (alloy AX30) with a
      fluoride (MgF(2) sponge, n = 24, porosity 63 +/- 6 %, pore size 394 +/- 26 MUm)
      and with a fluoride and additional calcium-phosphate coating (CaP sponge, n = 24,
      porosity 6 +/- 4 %, pore size 109 +/- 37 MUm) were evaluated over 6, 12 and 24
      weeks in rabbit femurs. Empty drill holes (n = 12) served as controls. Clinical
      and radiological examinations, in vivo and ex vivo MU-computed tomographies and
      histological examinations were performed. Clinically both sponge types were
      tolerated well. Radiographs and XtremeCT evaluations showed bone changes
      comparable to controls and mild gas formation. The MUCT80 depicted a higher and
      more inhomogeneous degradation of the CaP sponges. Histomorphometrically, the
      MgF(2) sponges resulted in the highest bone and osteoid fractions and were
      integrated superiorly into the bone. Histologically, the CaP sponges showed more
      inflammation and lower vascularization. MgF(2) sponges turned out to be better
      biocompatible and promising, biodegradable bone replacements.

PMID- 23160912
TI  - Topographical analysis of the femoral components of ex vivo total knee
      replacements.
AB  - With greater numbers of primary knee replacements now performed in younger
      patients there is a demand for improved performance. Surface roughness of the
      femoral component has been proposed as a causative mechanism for premature
      prosthesis failure. Nineteen retrieved total knee replacements were analysed
      using a non-contacting profilometer to measure the femoral component surface
      roughness. The Hood technique was used to analyse the wear and surface damage of
      the matching ultra-high molecular weight polyethylene (UHMWPE) tibial components.
      All femoral components were shown to be up to 11* rougher after their time in
      vivo while 95 % showed a change in skewness, further indicating wear. This
      increase in roughness occurred relatively soon after implantation (within 1 year)
      and remained unchanged thereafter. Mostly, this roughness was more apparent on
      the lateral condyle than the medial. This increased femoral surface roughness
      likely led to damage of the UHMWPE tibial component and increased Hood scores.

PMID- 23160913
TI  - Zinc-substituted hydroxyapatite: a biomaterial with enhanced bioactivity and
      antibacterial properties.
AB  - Hydroxyapatite (HA) is a synthetic biomaterial and has been found to promote new
      bone formation when implanted in a bone defect site. However, its use is often
      limited due to its slow osteointegration rate and low antibacterial activity,
      particularly where HA has to be used for long term biomedical applications. This
      work will describe the synthesis and detailed characterization of zinc
      substituted HA (ZnHA) as an alternative biomaterial to HA. ZnHA containing 1.6
      wt% Zn was synthesized via a co-precipitation reaction between calcium hydroxide,
      orthophosphoric acid and zinc nitrate hexahydrate. Single-phase ZnHA particles
      with a rod-like morphology measuring ~50 nm in length and ~15 nm in width, were
      obtained and characterized using transmission electron microscopy and X-ray
      diffraction. The substitution of Zn into HA resulted in a decrease in both the a-
      and c-axes of the unit cell parameters, thereby causing the HA crystal structure
      to alter. In vitro cell culture work showed that ZnHA possessed enhanced
      bioactivity since an increase in the growth of human adipose-derived mesenchymal
      stem cells along with the bone cell differentiation markers, were observed. In
      addition, antibacterial work demonstrated that ZnHA exhibited antimicrobial
      capability since there was a significant decrease in the number of viable
      Staphylococcus aureus bacteria after in contact with ZnHA.

PMID- 23160914
TI  - Gelatin microparticles aggregates as three-dimensional scaffolding system in
      cartilage engineering.
AB  - A three-dimensional (3D) scaffolding system for chondrocytes culture has been
      produced by agglomeration of cells and gelatin microparticles with a mild
      centrifuging process. The diameter of the microparticles, around 10 MU, was
      selected to be in the order of magnitude of the chondrocytes. No gel was used to
      stabilize the construct that maintained consistency just because of cell and
      extracellular matrix (ECM) adhesion to the substrate. In one series of samples
      the microparticles were charged with transforming growth factor, TGF-beta1. The
      kinetics of growth factor delivery was assessed. The initial delivery was
      approximately 48 % of the total amount delivered up to day 14. Chondrocytes that
      had been previously expanded in monolayer culture, and thus dedifferentiated,
      adopted in this 3D environment a round morphology, both with presence or absence
      of growth factor delivery, with production of ECM that intermingles with gelatin
      particles. The pellet was stable from the first day of culture. Cell viability
      was assessed by MTS assay, showing higher absorption values in the cell/unloaded
      gelatin microparticle pellets than in cell pellets up to day 7. Nevertheless the
      absorption drops in the following culture times. On the contrary the cell
      viability of cell/TGF-beta1 loaded gelatin microparticle pellets was constant
      during the 21 days of culture. The formation of actin stress fibres in the
      cytoskeleton and type I collagen expression was significantly reduced in both
      cell/gelatin microparticle pellets (with and without TGF-beta1) with respect to
      cell pellet controls. Total type II collagen and sulphated glycosaminoglycans
      quantification show an enhancement of the production of ECM when TGF-beta1 is
      delivered, as expected because this growth factor stimulate the chondrocyte
      proliferation and improve the functionality of the tissue.

PMID- 23160916
TI  - Chlamydia pneumoniae and osteoporosis-associated bone loss: a new risk factor?
AB  - We found an association between the presence of Chlamydia pneumoniae DNA both in
      osteoporotic bone tissue and peripheral blood mononuclear cells (PBMCs) and the
      increase in circulating resorptive cytokines. INTRODUCTION: Our study was
      designed to determine whether C. pneumoniae infection may be involved in
      osteoporosis-associated bone loss. METHODS: The study included 59 women
      undergoing hip joint replacement surgery for femoral neck fracture: 32 with
      osteoporosis and 27 with osteoarthritis. A total of 118 tissue specimens (59 bone
      tissues, 59 PBMCs) were examined for C. pneumoniae DNA by real-time polymerase
      chain reaction (PCR). Serum levels of soluble receptor activator of nuclear
      factor kappa B ligand (sRANKL), osteoprotegerin (OPG), interleukin (IL)-1beta,
      tumor necrosis factor-alpha, and IL-6 were also measured. RESULTS: C. pneumoniae
      DNA was detected in osteoporotic bone tissue whereas it was not found in non
      osteoporotic bone tissue (p < 0.05). A significantly higher rate of C. pneumoniae
      DNA (p < 0.05) was found in PBMCs of osteoporotic patients than in those of
      osteoarthritis patients. Among osteoporotic patients, serum sRANKL, IL-1, and IL
      6 concentrations as well as sRANKL/OPG ratio significantly differ between
      patients with bone tissue and PBMCs positive to C. pneumoniae and C. pneumoniae
      negative patients. CONCLUSION: The association between the presence of C.
      pneumoniae DNA, both in bone tissue and PBMCs, and the increase in sRANKL/OPG
      ratio as well as in IL-1beta and IL-6 levels observed in osteoporotic patients
      suggests C. pneumoniae infection as a new risk factor for osteoporosis.

PMID- 23160917
TI  - Peripheral arterial disease increases the risk of subsequent hip fracture in
      older men: the Health in Men Study.
AB  - The aim of the present study was to assess whether peripheral arterial disease is
      associated with an increased risk of hip fracture in a cohort of 12,094 older
      men. There was no association between claudication and hip fracture, but there
      was a significant association with an ankle brachial index (ABI) <0.9.
      INTRODUCTION: It is uncertain whether peripheral arterial disease (PAD) is
      associated with an increased risk of subsequent hip fracture. The aim of the
      present study was to assess this in a large cohort of men aged 65 years and over.
      METHODS: Claudication was assessed by means of the Edinburgh Claudication
      Questionnaire in 12,094 men, and the ABI was measured in 4,321 of these men.
      Hospitalisations with hip fracture were identified by record linkage. The
      association between both claudication and an ABI <0.9 and subsequent hip
      fractures was assessed using survival curves and Cox regression models. RESULTS:
      Amongst the 12,094 men, the baseline prevalence of claudication according to the
      ECQ was 5.3 %. Amongst the 4,321 men with ABI results, the prevalence of an ABI
      <0.9 was 11.7 %. Of the 506 men with an ABI <0.9, 129 (25.5 %) also had
      claudication. Over a median (range) follow-up of 10.8 (0.3-12.7) years, 343 (2.8
      %) of the 12,094 men were admitted to hospital with a hip fracture. There was no
      association between claudication and subsequent hip fractures (hazard ratio (HR)
      = 0.95; 95 % confidence interval (CI), 0.60, 1.52). Over a median (range) follow
      up of 11.1 (0.06-12.3) years 135 (3.1 %) of the 4,321 men with ABI data were
      admitted to hospital with hip fractures. There was a significant association
      between an ABI <0.9 and subsequent hip fracture (HR = 1.69; 95 % CI, 1.08, 2.63).
      CONCLUSION: Older men with PAD defined as ABI < 0.9 are at increased risk of hip
      fracture, whereas the symptom of claudication is not an independent predictor of
      hip fracture.

PMID- 23160915
TI  - How important is vitamin D in preventing infections?
AB  - Interaction with the immune system is one of the most recently established
      nonclassic effects of vitamin D (VitD). For many years, this was considered to be
      limited to granulomatous diseases in which synthesis of active 1,25
      dihydroxyvitamin D3 (1,25(OH)2D3) or calcitriol is known to be increased.
      However, recent reports have supported a role for 1,25(OH)2D3 in promoting normal
      function of the innate and adaptive immune systems. Crucially, these effects seem
      to be mediated not only by the endocrine function of circulating calcitriol but
      also via paracrine (i.e., refers to effects to adjacent or nearby cells) and/or
      intracrine activity (i.e., refers to a hormone acting inside a cell) of
      1,25(OH)2D3 from its precursor 25(OH)D3, the main circulating metabolite of VitD.
      The ability of this vitamin to influence human immune responsiveness seems to be
      highly dependent on the 25(OH)D3 status of individuals and may lead to aberrant
      response to infection or even to autoimmunity in those who are lacking VitD. The
      potential health significance of this has been underlined by increasing awareness
      of impaired status in populations across the globe. This review will examine the
      current understanding of how VitD status may modulate the responsiveness of the
      human immune system. Furthermore, we discuss how it may play a role in host
      resistance to common pathogens and how effective is its supplementation for
      treatment or prevention of infectious diseases in humans.

PMID- 23160918
TI  - Molecular modeling-based inclusion mechanism and stability studies of doxycycline
      and hydroxypropyl-beta-cyclodextrin complex for ophthalmic delivery.
AB  - The aim of the present study was to prepare a stable complex of doxycycline
      (Doxy) and hydroxypropyl-beta-cyclodextrin (HPbetaCD) for ophthalmic delivery and
      investigate the inclusion mechanism and the inclusion effects on the stability of
      Doxy. The Doxy/HPbetaCD complex was prepared by solution stirring and then
      characterized by scanning electron microscopy and ultraviolet spectroscopy. Based
      on results of nuclear magnetic resonance, molecular model of Doxy/HPbetaCD
      complex was established using computational simulation of PM3 method implemented
      in Gaussian 03. Stabilities of Doxy/HPbetaCD complex in both aqueous solution and
      solid state at 25 degrees C were evaluated by HPLC. Finally, in vitro
      antibacterial activity of the Doxy/HPbetaCD complex was evaluated by disk
      diffusion test. It was found that the stabilities of Doxy/HPbetaCD complex in
      both aqueous solution and solid state were improved obviously as compared with
      Doxy alone. This stability enhancement is consistent with the inclusion mechanism
      between HPbetaCD and Doxy, which showed that the unstable site of Doxy molecule
      at 6-CH3 was protected in the hydrophobic cavity of HPbetaCD, additionally, the
      chelation of Mg2+ provided a synergetic protection of the other unstable site of
      Doxy at 4-N(CH3)2. The antibacterial activity results indicated that
      Doxy/HPbetaCD complex might have potential for clinical applications.

PMID- 23160919
TI  - Genotyping of human papillomavirus in paraffin embedded cervical tissue samples
      from women in Ethiopia and the Sudan.
AB  - Cervical cancer is the most frequent female malignancy in most developing
      countries. Previous studies have demonstrated a strong association of human
      papillomavirus (HPV) infection with dysplasia and carcinoma of the uterine
      cervix. The objective of this study was to identify the prevailing HPV genotypes
      responsible for the development of cervical cancer among women in Ethiopia and
      the Sudan. A molecular characterization of HPV was done on 245 paraffin embedded
      cervical biopsy samples collected from the two countries. Amplification of HPV
      and subsequent genotyping was done using SPF10 primers and Line probe assay. Of
      samples collected from Ethiopian patients, 93% (149/160) and 13% (21/160) had
      high risk and low risk HPV genotypes, respectively. Among samples collected from
      the Sudan, 94% (80/85) harbored high risk and 11.7% (10/85) low risk HPV
      genotypes. Human papillomavirus 16 was the most frequent genotype identified in
      samples from Ethiopia (91%, 136/149) and the Sudan (82.5%, 66/80). HPV 52, 58,
      and 18 were the second, third and fourth common genotypes identified in Ethiopia,
      whereas HPV 18, 45, and 52 were the second, third, and fourth genotypes
      identified in samples collected from the Sudan. Thus, individuals living in
      different geographical localities should receive vaccines based on the specific
      genotypes circulating in the area and a vaccine targeting HPV 16, 18, 45, 52, and
      58 may be optimal for the control of cervical cancer in the two countries.

PMID- 23160920
TI  - Pharmacokinetic and pharmacodynamic profiles of a fixed-dose combination of
      olmesartan medoxomil and amlodipine in healthy Chinese males and females.
AB  - OBJECTIVES: This study investigated the pharmacokinetics and pharmacodynamics of
      a fixed-dose combination (FDC) tablet of olmesartan medoxomil 20 mg and
      amlodipine 5 mg (CS-8663) in healthy Chinese subjects. METHODS: This single
      centre, open-label study was conducted in five healthy males and five females
      aged 18-45 years. Subjects received a single oral dose of an olmesartan
      medoxomil/amlodipine 20 mg/5 mg tablet on Day 1 under fasting conditions, and
      after a wash-out period they received the same dose once daily from Day 15 to Day
      24. Serial blood samples were collected at predefined time-points to measure the
      plasma concentrations of olmesartan and amlodipine during the single-dose and the
      multiple-dose period. Meanwhile, blood pressure and heart rate were repeatedly
      taken to delineate the pharmacodynamic profiles. Safety was assessed throughout
      the study. RESULTS: After oral administration, the peak concentrations of
      olmesartan and amlodipine were reached in a median time of 2 and 6 h,
      respectively. The elimination half-life of amlodipine is more than twice as long
      as that of olmesartan. Steady states of both compounds were attained after once
      daily dosing for 8 days. Similar significant reductions of systolic and diastolic
      blood pressure were observed after a single dose of an olmesartan
      medoxomil/amlodipine 20 mg/5 mg FDC tablet. In comparison, multiple doses of
      olmesartan medoxomil/amlodipine 20 mg/5 mg tablets lowered the daily pre-dose BP
      level and led to smaller BP changes after the last dose. Heart rate increments
      were larger and more sustained after multiple doses than during the single-dose
      period. Females showed more systolic BP reductions than males despite inter-sex
      similarity in pharmacokinetics. Treatment with olmesartan medoxomil/amlodipine 20
      mg/5 mg FDC tablets was safe and well tolerated. CONCLUSION: After single and
      multiple doses of olmesartan medoxomil/amlodipine 20 mg/5 mg FDC tablets the
      pharmacokinetic profiles of olmesartan or amlodipine were comparable to those
      reported for monotherapy with olmesartan medoxomil or amlodipine, except that the
      elimination half-life of olmesartan was longer because of the longer time course
      over which pharmacokinetic blood sampling was carried out in this study. The
      response profiles of BP indicate a concentration-dependent antihypertensive
      effect of the olmesartan medoxomil/amlodipine 20 mg/5 mg FDC tablet after a
      single dose and stabilization of such effects after multiple doses.

PMID- 23160921
TI  - Characterization and stabilization of recombinant human protein pentraxin (rhPTX
      2).
AB  - The potential human therapeutic protein pentraxin (PTX-2) is a large,
      glycosylated plasma protein consisting of five monomers that self-associate
      noncovalently into a pentameric, ring-like structure. The structural integrity
      and conformational stability of recombinant human PTX-2 (rhPTX-2) as a function
      of temperature and pH is described in conjunction with the identification of
      stabilizing excipients that improve the protein's physical stability. The monomer
      consisted primarily of two glycosylated forms (25,171 and 25,462 Da) as
      determined by mass spectrometry. The protein was approximately 82%-97% pentamer
      in solution with smaller amounts of decamer and aggregate as measured by
      analytical ultracentrifugation and size-exclusion chromatography (SEC).
      Comprehensive biophysical characterization using an empirical phase diagram
      approach demonstrates that rhPTX-2 is conformationally stable over a wide pH
      range (6.0-8.5) and at temperatures below 65 degrees C-75 degrees C. Formation of
      soluble aggregates was identified as a major physical degradation pathway of
      rhPTX-2 in solution under accelerated storage conditions. A series of effective
      stabilizers was identified by SEC analysis including disaccharides, sugar
      alcohols, citrate, as well as neutral and charged amino acids. The preformulation
      characterization data and stability profile presented in this work enable future
      studies for rhPTX-2 formulation development.

PMID- 23160922
TI  - Bioconversion of Agave tequilana fructans by exo-inulinases from indigenous
      Aspergillus niger CH-A-2010 enhances ethanol production from raw Agave tequilana
      juice.
AB  - Agave tequilana fructans are the source of fermentable sugars for the production
      of tequila. Fructans are processed by acid hydrolysis or by cooking in ovens at
      high temperature. Enzymatic hydrolysis is considered an alternative for the
      bioconversion of fructans. We previously described the isolation of Aspergillus
      niger CH-A-2010, an indigenous strain that produces extracellular inulinases.
      Here we evaluated the potential application of A. niger CH-A-2010 inulinases for
      the bioconversion of A. tequilana fructans, and its impact on the production of
      ethanol. Inulinases were analyzed by Western blotting and thin layer
      chromatography. Optimal pH and temperature conditions for inulinase activity were
      determined. The efficiency of A. niger CH-A-2010 inulinases was compared with
      commercial enzymes and with acid hydrolysis. The hydrolysates obtained were
      subsequently fermented by Saccharomyces cerevisiae to determine the efficiency of
      ethanol production. Results indicate that A. niger CH-A-2010 predominantly
      produces an exo-inulinase activity. Optimal inulinase activity occurred at pH 5.0
      and 50  degrees C. Hydrolysis of raw agave juice by CH-A-2010 inulinases yielded
      33.5 g/l reducing sugars, compared with 27.3 g/l by Fructozyme((r)) (Novozymes
      Corp, Bagsvaerd, Denmark) and 29.4 g/l by acid hydrolysis. After fermentation of
      hydrolysates, we observed that the conversion efficiency of sugars into ethanol
      was 97.5 % of the theoretical ethanol yield for enzymatically degraded agave
      juice, compared to 83.8 % for acid-hydrolyzed juice. These observations indicate
      that fructans from raw Agave tequilana juice can be efficiently hydrolyzed by
      using A. niger CH-A-2010 inulinases, and that this procedure impacts positively
      on the production of ethanol.

PMID- 23160923
TI  - Characterization of three new carboxylic ester hydrolases isolated by functional
      screening of a forest soil metagenomic library.
AB  - Three new lipolytic genes were isolated from a forest soil metagenomic library by
      functional screening on tributyrin agar plates. The genes SBLip1, SBLip2 and
      SBLip5.1 respectively encode polypeptides of 445, 346 and 316 amino acids.
      Phylogenetic analyses revealed that SBLip2 and SBLip5.1 belong to bacterial
      esterase/lipase family IV, whereas SBLip1 shows similarity to class C beta
      lactamases and is thus related to esterase family VIII. The corresponding genes
      were overexpressed and their products purified by affinity chromatography for
      characterization. Analyses of substrate specificity with different p-nitrophenyl
      esters showed that all three enzymes have a preference for short-acyl-chain p
      nitrophenyl esters, a feature of carboxylesterases as opposed to lipases. The
      beta-lactamase activity of SBLip1, measured with the chromogenic substrate
      nitrocefin, was very low. The three esterases have the same optimal pH (pH 10)
      and remain active across a relatively broad pH range, displaying more than 60 %
      activity between pH 6 and 10. The temperature optima determined were 35  degrees
      C for SBLip1, 45  degrees C for SBLip2 and 50  degrees C for SBLip5.1. The three
      esterases displayed different levels of tolerance to salts, solvents and
      detergents, SBLip2 being overall more tolerant to high concentrations of solvent
      and SBLip5.1 less affected by detergents.

PMID- 23160924
TI  - Inhibition of the proliferation of acquired aromatase inhibitor-resistant breast
      cancer cells by histone deacetylase inhibitor LBH589 (panobinostat).
AB  - Aromatase inhibitors (AIs) are important drugs for treating postmenopausal
      patients with hormone receptor-positive breast cancer. However, acquired
      resistance to AI therapies is a significant problem. Our study has revealed that
      the histone deacetylase inhibitor LBH589 treatment abrogated growth of AI
      resistant cells in vitro and in vivo, causing cell cycle G2/M arrest and induced
      apoptosis. LBH589 treatment also reduced the level of NF-kappaB1 which is
      overexpressed when AI resistance develops. Analyzing paired tumor specimens from
      12 patients, we found that NF-kappaB1 expression was increased in recurrent AI
      resistant tumors as compared to the paired primary tumors before AI treatment.
      This finding was consistent with up-regulated NF-kappaB1 expression seen in a
      collection of well-established AI-resistant cell lines. Furthermore, knockdown of
      NF-kappaB1 expression significantly suppressed the proliferation of AI-resistant
      cells. Treatment of AI-resistant cell lines with LBH589 suppressed NF-kappaB1
      mRNA and protein expression. In addition, LBH589 treatment abrogated growth of AI
      resistant tumors in mice, and was associated with significantly decreased levels
      of NF-kappaB1 in tumors. In all, our findings strongly support further
      investigation of LBH589 as a novel therapeutic strategy for patients with AI
      resistant breast cancer, in part by suppressing the NF-kappaB1 pathway.

PMID- 23160925
TI  - Heparins modulate the IFN-gamma-induced production of chemokines in human breast
      cancer cells.
AB  - Heparins seem to improve survival in patients with advanced malignancies
      independently of their anticoagulatory function. As the treatment options in
      advanced and metastatic breast cancer are still very limited, heparins might be
      an interesting addition to the existing systemic therapies. The interferon (IFN)
      gamma-inducible chemokines CXCL9 and CXCL10 play an essential role in the
      regulation of the immune milieu in malignant tumours, thereby being interesting
      targets for an immunological intervention. We therefore wanted to test whether
      heparins have an impact on the chemokines CXCL9 and CXCL10 as well as the IFN
      gamma signalling in human breast cancer cells in vitro. The well-established cell
      lines BT-474, MCF-7, SK-BR-3 and MDA-MB-231 were incubated with IFN-gamma,
      unfractionated heparin (UFH), different low molecular weight heparins (LMWHs) and
      the heparin-related polyanions danaparoid and dextran sulphate. The production of
      CXCL9 and CXCL10 was measured by ELISA and real-time RT-PCR, the phosphorylation
      of signal transducer and activator of transcription (STAT) 1 was detected by an
      in-cell western assay and the amount of cellular bound IFN-gamma was analysed by
      a high sensitivity ELISA. We observed that IFN-gamma induced CXCL9 and CXCL10
      production in MCF-7, SK-BR-3 and MDA-MB-231 cells but not in BT-474. UFH dose
      dependently inhibited the effect of IFN-gamma on the secretion and expression of
      CXCL9 and CXCL10. LMWHs and heparin-related compounds differentially modulated
      IFN-gamma-effects-the results depended on their molecular size and charge, but
      were independent of their anticoagulatory properties. As a reason for these
      heparin effects, we could show that the IFN-gamma-induced phosphorylation of
      STAT1 was modulated by heparins, caused by an interaction with the cellular
      binding of IFN-gamma. In conclusion, these results support the significance of
      the immunomodulatory properties of heparins independently of their classical
      anticoagulatory function. Heparin-derived sulphated polysaccharides with distinct
      molecular properties might thus be interesting candidates for new therapeutic
      strategies in breast cancer.

PMID- 23160926
TI  - Molecularly targeted gold nanoparticles enhance the radiation response of breast
      cancer cells and tumor xenografts to X-radiation.
AB  - The purpose of this study was to evaluate the effect of molecularly targeted gold
      nanoparticles (AuNPs) on tumor radiosensitization both in vitro and in vivo.
      Human Epidermal Growth Factor Receptor-2 (HER-2)-targeted AuNPs (Au-T) were
      synthesized by conjugating trastuzumab (Herceptin) to 30 nm AuNPs. In vitro, the
      cytotoxicity of Au-T or non-targeted AuNPs (Au-P) was assessed by gamma-H2AX
      immunofluorescence microscopy for DNA damage and clonogenic survival assays. In
      vivo, athymic mice bearing subcutaneous MDA-MB-361 xenografts were treated with a
      single dose of 11 Gy of 100 kVp X-rays 24 h after intratumoral injection of Au-T
      (~0.8 mg of Au) or no X-radiation. Normal tissue toxicity was determined by
      hematology or biochemistry parameters. The combination of Au-P or Au-T with X-ray
      exposure increased the formation of gamma-H2AX foci by 1.7 (P = 0.054) and 3.3 (P
      = 0.024) fold in comparison to X-radiation alone, respectively. The clonogenic
      survival of cells exposed to Au-T and X-rays was significantly lower from that of
      cells exposed to X-radiation alone, which translated to a dose enhancement factor
      of 1.6. In contrast, survival of cells exposed to Au-P and X-rays versus X
      radiation alone were not significantly different. In vivo, the combination of Au
      T and X-radiation resulted in regression of MDA-MB-361 tumors by 46 % as compared
      to treatment with X-radiation (16.0 % increase in tumor volume). No significant
      normal tissue toxicity was observed. Radiosensitization of breast cancer to X
      radiation with AuNPs was successfully achieved with an optimized therapeutic
      strategy of molecular targeting of HER-2 and intratumoral administration.

PMID- 23160927
TI  - Characterization of the ground state dynamics of proteorhodopsin by NMR and
      optical spectroscopies.
AB  - We characterized the dynamics of proteorhodopsin (PR), solubilized in diC7PC, a
      detergent micelle, by liquid-state NMR spectroscopy at T = 323 K. Insights into
      the dynamics of PR at different time scales could be obtained and dynamic hot
      spots could be identified at distinct, functionally relevant regions of the
      protein, including the BC loop, the EF loop, the N-terminal part of helix F and
      the C-terminal part of helix G. We further characterize the dependence of the
      photocycle on different detergents (n-Dodecyl beta-D-maltoside DDM; 1,2
      diheptanoyl-sn-glycero-3-phosphocholine diC7PC) by ultrafast time-resolved UV/VIS
      spectroscopy. While the photocycle intermediates of PR in diC7PC and DDM exhibit
      highly similar spectral characteristics, significant changes in the population of
      these intermediates are observed. In-situ NMR experiments have been applied to
      characterize structural changes during the photocycle. Light-induced chemical
      shift changes detected during the photocycle in diC7PC are very small, in line
      with the changes in the population of intermediates in the photocycle of
      proteorhodopsin in diC7PC, where the late O-intermediate populated in DDM is
      missing and the population is shifted towards an equilibrium of intermediates
      states (M, N, O) without accumulation of a single populated intermediate.

PMID- 23160928
TI  - Formaldehyde increases intracellular calcium concentration in primary cultured
      hippocampal neurons partly through NMDA receptors and T-type calcium channels.
AB  - OBJECTIVE: Formaldehyde at high concentrations is a contributor to air pollution.
      It is also an endogenous metabolic product in cells, and when beyond
      physiological concentrations, has pathological effects on neurons. Formaldehyde
      induces mis-folding and aggregation of neuronal tau protein, hippocampal neuronal
      apoptosis, cognitive impairment and loss of memory functions, as well as
      excitation of peripheral nociceptive neurons in cancer pain models. Intracellular
      calcium ([Ca(2+)](i)) is an important intracellular messenger, and plays a key
      role in many pathological processes. The present study aimed to investigate the
      effect of formaldehyde on [Ca(2+)](i) and the possible involvement of N-methyl-D
      aspartate receptors (NMDARs) and T-type Ca(2+) channels on the cell membrane.
      METHODS: Using primary cultured hippocampal neurons as a model, changes of
      [Ca(2+)](i) in the presence of formaldehyde at a low concentration were detected
      by confocal laser scanning microscopy. RESULTS: Formaldehyde at 1 mmol/L
      approximately doubled [Ca(2+)](i). (2R)-amino-5-phosphonopentanoate (AP5, 25
      MUmol/L, an NMDAR antagonist) and mibefradil (MIB, 1 MUmol/L, a T-type Ca(2+)
      channel blocker), given 5 min after formaldehyde perfusion, each partly inhibited
      the formaldehyde-induced increase of [Ca(2+)](i), and this inhibitory effect was
      reinforced by combined application of AP5 and MIB. When applied 3 min before
      formaldehyde perfusion, AP5 (even at 50 MUmol/L) did not inhibit the formaldehyde
      induced increase of [Ca(2+)](i), but MIB (1 MUmol/L) significantly inhibited this
      increase by 70%. CONCLUSION: These results suggest that formaldehyde at a low
      concentration increases [Ca(2+)](i) in cultured hippocampal neurons; NMDARs and T
      type Ca(2+) channels may be involved in this process.

PMID- 23160929
TI  - Immunoenrichment microwave and magnetic proteomics for quantifying CD47 in the
      experimental autoimmune encephalomyelitis model of multiple sclerosis.
AB  - We hypothesized that quantitative MS/MS-based proteomics at multiple time points,
      incorporating immunoenrichment prior to rapid microwave and magnetic (IM(2) )
      sample preparation, might enable correlation of the relative expression of CD47
      and other low abundance proteins to disease progression in the experimental
      autoimmune encephalomyelitis (EAE) animal model of multiple sclerosis. To test
      our hypothesis, anti-CD47 antibodies were used to enrich for low abundance CD47
      prior to microwave and magnetic proteomics in EAE. Decoding protein expression at
      each time point, with CD47-immunoenriched samples and targeted proteomic
      analysis, enabled peptides from the low abundance proteins to be precisely
      quantified throughout disease progression, including: CD47: 86-99, corresponding
      to the "marker of self" overexpressed by myelin that prevents phagocytosis, or
      "cellular devouring," by microglia and macrophages; myelin basic protein: 223
      228, corresponding to myelin basic protein; and migration inhibitory factor: 79
      87, corresponding to a proinflammatory cytokine that inhibits macrophage
      migration. While validation in a larger cohort is underway, we conclude that
      IM(2) proteomics is a rapid method to precisely quantify peptides from CD47 and
      other low abundance proteins throughout disease progression in EAE. This is
      likely due to improvements in selectivity and sensitivity, necessary to partially
      overcome masking of low abundance proteins by high abundance proteins and improve
      dynamic range.

PMID- 23160930
TI  - Comparison of the efficacy of ribavirin plus peginterferon alfa-2b for chronic
      hepatitis C infection in patients with and without coagulation disorders.
AB  - Many patients with coagulation disorders are infected with hepatitis C virus
      (HCV) that advances to end stage liver disease, resulting in an increased number
      of deaths. The efficacy of ribavirin and peginterferon combination therapy for
      chronic HCV infection in patients with coagulation disorders has not been
      clarified fully. The aim of this study was to evaluate the efficacy and
      tolerability of combination therapy in this patient population compared with
      patients who are infected with HCV and do not have coagulation disorders. A total
      of 226 consecutive chronic hepatitis C patients were treated with combination
      therapy and divided into two groups: patients with (n = 23) and without
      coagulation disorders (n = 203). Clinical characteristics, sustained virological
      response rates obtained by an intention-to-treat analysis, and combination
      therapy discontinuation rates were compared between the two groups. The sustained
      virological response rates did not differ significantly between patients with and
      without coagulation disorders (65.2% vs. 47.8% by intention-to-treat analysis).
      According to a multivariate analysis, age, alanine aminotransferase, gamma
      glutamyltransferase, and HCV genotype were associated significantly with a
      sustained virological response, whereas whether a patient had a coagulation
      disorder did not affect the sustained virological response. In conclusion,
      combination therapy for chronic hepatitis C was comparably effective between
      patients with and without coagulation disorders and did not result in adverse
      bleeding.

PMID- 23160931
TI  - The effect of C-vacancy on hydrogen storage and characterization of H2 modes on
      Ti functionalized C60 fullerene a first principles study.
AB  - Density functional theory calculations were performed to examine the effect of a
      C vacancy on the physisorption of H(2) onto Ti-functionalized C(60) fullerene
      when H(2) is oriented along the x-, y-, and z-axes of the fullerene. The effect
      of the C vacancy on the physisorption modes of H(2) was investigated as a
      function of H(2) binding energy within the energy window (-0.2 to -0.6 eV)
      targeted by the Department of Energy (DOE), and as functions of a variety of
      other physicochemical properties. The results indicate that the preferential
      orientations of H(2) in the defect-free (i.e., no C vacancy) C(60)TiH(2) complex
      are along the x- and y-axes of C(60) (with adsorption energies of -0.23 and -0.21
      eV, respectively), making these orientations the most suitable ones for hydrogen
      storage, in contrast to the results obtained for defect-containing fullerenes.
      The defect-containing (i.e., containing a C vacancy) C(59)TiH(2) complex do not
      exhibit adsorption energies within the targeted energy range. Charge transfer
      occurs from Ti 3d to C 2p of the fullerene. The binding of H(2) is dominated by
      the pairwise support-metal interaction energy E(i)(Cn...Ti), and the role of the
      fullerene is not restricted to supporting the metal. The C vacancy enhances the
      adsorption energy of Ti, in contrast to that of H(2). A significant reduction in
      the energy gap of the pristine C(60) fullerene is observed when TiH(2) is
      adsorbed by it. While the C( n ) fullerene readily participates in nucleophilic
      processes, the adjacent TiH(2) fragment is available for electrophilic processes.

PMID- 23160932
TI  - B30H8, B39H9(2-), B42H10, B48H10, and B72H12: polycyclic aromatic snub hydroboron
      clusters analogous to polycyclic aromatic hydrocarbons.
AB  - Calculations performed at the ab initio level using the recently reported planar
      concentric pi-aromatic B(18)H(6)(2+)(1) [Chen Q et al. (2011) Phys Chem Chem Phys
      13:20620] as a building block suggest the possible existence of a new class of
      B(3n)H(m) polycyclic aromatic hydroboron (PAHB) clusters-B(30)H(8)(2),
      B(39)H(9)(2-)(3), B(42)H(10)(4/5), B(48)H(10)(6), and B(72)H(12)(7)-which appear
      to be the inorganic analogs of the corresponding C(n)H(m) polycyclic aromatic
      hydrocarbon (PAHC) molecules naphthalene C(10)H(8), phenalenyl anion C(13)H(9)(
      ), phenanthrene/anthracene C(14)H(10), pyrene C(16)H(10), and coronene
      C(24)H(12), respectively, in a universal atomic ratio of B:C = 3:1. Detailed
      canonical molecular orbital (CMO), adaptive natural density partitioning (AdNDP),
      and electron localization function (ELF) analyses indicate that, as they are
      hydrogenated fragments of a boron snub sheet [Zope RR, Baruah T (2010) Chem Phys
      Lett 501:193], these PAHB clusters are aromatic in nature, and exhibit the
      formation of islands of both sigma- and pi-aromaticity. The predicted ionization
      potentials of PAHB neutrals and electron detachment energies of small PAHB
      monoanions should permit them to be characterized experimentally in the future.
      The results obtained in this work expand the domain of planar boron-based
      clusters to a region well beyond B(20), and experimental syntheses of these snub
      B(3n)H(m) clusters through partial hydrogenation of the corresponding bare B(3n)
      may open up a new area of boron chemistry parallel to that of PAHCs in carbon
      chemistry.

PMID- 23160933
TI  - Conformational flexibility of the ErbB2 ectodomain and trastuzumab antibody
      complex as revealed by molecular dynamics and principal component analysis.
AB  - Human epidermal growth factor receptor 2 (ErbB2) is a transmembrane oncoprotein
      that is over expressed in breast cancer. A successful therapeutic treatment is a
      monoclonal antibody called trastuzumab which interacts with the ErbB2
      extracellular domain (ErbB2-ECD). A better understanding of the detailed
      structure of the receptor-antibody interaction is indeed of prime interest for
      the design of more effective anticancer therapies. In order to discuss the
      flexibility of the complex ErbB2-ECD/trastuzumab, we present, in this study, a
      multi-nanosecond molecular dynamics simulation (MD) together with an analysis of
      fluctuations, through a principal component analysis (PCA) of this system.
      Previous to this step and in order to validate the simulations, we have performed
      a detailed analysis of the variable antibody domain interactions with the
      extracellular domain IV of ErbB2. This structure has been statically elucidated
      by x-ray studies. Indeed, the simulation results are in excellent agreement with
      the available experimental information during the full trajectory. The PCA shows
      eigenvector fluctuations resulting in a hinge motion in which domain II and C(H)
      domains approach each other. This move is likely stabilized by the formation of H
      bonds and salt bridge interactions between residues of the dimerization arm in
      the domain II and trastuzumab residues located in the C(H) domain. Finally, we
      discuss the flexibility of the MD/PCA model in relation with the static x-ray
      structure. A movement of the antibody toward the dimerization domain of the ErbB2
      receptor is reported for the first time. This finding could have important
      consequences on the biological action of the monoclonal antibody.

PMID- 23160934
TI  - Comparison of the structural characteristics of Cu(2+)-bound and unbound alpha
      syn12 peptide obtained in simulations using different force fields.
AB  - The effects of Cu(2+) binding and the utilization of different force fields when
      modeling the structural characteristics of alpha-syn12 peptide were investigated.
      To this end, we performed extensive temperature replica exchange molecular
      dynamics (T-REMD) simulations on Cu(2+)-bound and unbound alpha-syn12 peptide
      using the GROMOS 43A1, OPLS-AA, and AMBER03 force fields. Each replica was run
      for 300 ns. The structural characteristics of alpha-syn12 peptide were studied
      based on backbone dihedral angle distributions, free-energy surfaces obtained
      with different reaction coordinates, favored conformations, the formation of
      different Turn structures, and the solvent exposure of the hydrophobic residues.
      The findings show that AMBER03 prefers to sample helical structures for the
      unbound alpha-syn12 peptide and does not sample any beta-hairpin structure for
      the Cu(2+)-bound alpha-syn12 peptide. In contrast, the central structure of the
      major conformational clusters for the Cu(2+)-bound and unbound alpha-syn12
      peptide according to simulations performed using the GROMOS 43A1 and OPLS-AA
      force fields is a beta-hairpin with Turn(9-6). Cu(2+) can also promote the
      formation of the beta-hairpin and increase the solvent exposure of hydrophobic
      residues, which promotes the aggregation of alpha-syn12 peptide. This study can
      help us to understand the mechanisms through which Cu(2+) participates in the
      fibrillation of alpha-syn12 peptide at the atomic level, which in turn represents
      a step towards elucidating the nosogenesis of Parkinson's disease.

PMID- 23160935
TI  - Theoretical study on aluminum carbide endohedral fullerene-Al4C@C80.
AB  - The possibility of a new endohedral fullerene with a trapped aluminum carbide
      cluster, Al(4)C@C(80)-I( h ), was theoretical investigated. The geometries and
      electronic properties of it were investigated using density functional theory
      methods. The Al(4)C unit formally transfers six electrons to the C(80) cage which
      induces stabilization of Al(4)C@C(80). A favorable binding energy, relatively
      large HOMO-LUMO gap, electron affinities and ionization potentials suggested the
      Al(4)C@C(80) is rather stable. The analysis of vertical ionization potential and
      vertical electron affinity indicate Al(4)C@C(80) is a good electron acceptor.

PMID- 23160936
TI  - Isolation technique and proteomic analysis of the erythrocyte ghosts of red-eared
      turtle (Trachemys scripta).
AB  - To proceed proteomic analysis of erythrocyte of the red-eared turtle Trachemys
      scripta, a method for obtaining turtle erythrocyte ghosts (TEG) was first
      developed. After hypotonic lysis using a special buffer, forcing the erythrocyte
      through the syringe with an "N"-shaped needle, applying low speed homogenizing
      and differential centrifugation, highly purified TEG fractions were obtained. The
      isolated TEG proteins were treated with in-gel digestion separated by SDS-PAGE or
      in-solution digestion followed by HPLC predissociation, and then identified by
      nano-ESI-LC MS/MS techniques. A total of 169 TEG proteins was identified,
      validated, and categorized. Among these proteins, tubulins, and cell-surface
      located F-type ATP synthase revealed important information into the super
      tolerance of Trachemys scripta in anoxia and low temperature exposure.
      Altogether, this study not only provided a method to isolate high quality TEG and
      a dataset of comprehensive characterization of TEG proteins, but also provides a
      tool for proteomic research of all nucleated red blood cells, and thus opened a
      new research field for exploring the mechanisms of super tolerance of turtles in
      harsh environment.

PMID- 23160937
TI  - Methylphenidate : a treatment for Parkinson's disease?
AB  - Parkinson's disease (PD) affects about 1 % of the population over the age of 60
      years and is characterized by a combination of rest tremor, bradykinesia,
      rigidity, postural instability, stooped posture and freezing of gait (FoG).
      However, the clinical spectrum also spans a wide range of non-motor symptoms,
      such as depression, apathy, cognitive disorders, sleepiness, fatigue and pain.
      Given that the loss of dopamine in the striatum is the primary pathochemical
      hallmark in PD, pharmacological treatment of the disease has focused on restoring
      dopaminergic neurotransmission. The currently licensed dopaminergic treatments
      for PD modulate all the key steps in the dopamine transmission except the most
      powerful determinant of extracellular dopamine concentrations: the presynaptic
      dopamine transporter (DaT). Methylphenidate is a CNS stimulant that blocks the
      DaT and the noradrenaline (norepinephrine) transporter in the striatum and the
      prefrontal cortex in particular. Here, we report on and discuss the main open
      label studies and randomized controlled trials on the effect of methylphenidate
      on severe gait disorders (e.g. the FoG) and non-motor symptoms in advanced PD.
      The various pharmacodynamic effects of methylphenidate mean that the drug may
      have significant value in the treatment of PD. However, there is a lack of
      randomized controlled trials in this field. Furthermore, more rigorous selection
      of the types and doses of the associated dopaminergic treatments is required
      because these parameters may profoundly influence the mechanisms of action of
      methylphenidate and the clinical outcomes. Pharmacogenetic tools could be of use
      in better defining study patients as a function of their dopaminergic metabolism
      and drug responsiveness.

PMID- 23160938
TI  - CSF penetration by antiretroviral drugs.
AB  - Severe HIV-associated neurocognitive disorders (HAND), such as HIV-associated
      dementia, and opportunistic CNS infections are now rare complications of HIV
      infection due to comprehensive highly active antiretroviral therapy (HAART). By
      contrast, mild to moderate neurocognitive disorders remain prevalent, despite
      good viral control in peripheral compartments. HIV infection seems to provoke
      chronic CNS injury that may evade systemic HAART. Penetration of antiretroviral
      drugs across the blood-brain barrier might be crucial for the treatment of HAND.
      This review identifies and evaluates the available clinical evidence on CSF
      penetration properties of antiretroviral drugs, addressing methodological issues
      and discussing the clinical relevance of drug concentration assessment. Although
      a substantial number of studies examined CSF concentrations of antiretroviral
      drugs, there is a need for adequate, well designed trials to provide more valid
      drug distribution profiles. Neuropsychological benefits and neurotoxicity of
      potentially CNS-active drugs require further investigation before penetration
      characteristics will regularly influence therapeutic strategies and outcome.

PMID- 23160940
TI  - CB(1) receptor allosteric modulators display both agonist and signaling pathway
      specificity.
AB  - We have previously identified allosteric modulators of the cannabinoid CB(1)
      receptor (Org 27569, PSNCBAM-1) that display a contradictory pharmacological
      profile: increasing the specific binding of the CB(1) receptor agonist
      [(3)H]CP55940 but producing a decrease in CB(1) receptor agonist efficacy. Here
      we investigated the effect one or both compounds in a broad range of signaling
      endpoints linked to CB(1) receptor activation. We assessed the effect of these
      compounds on CB(1) receptor agonist-induced [(35)S]GTPgammaS binding, inhibition,
      and stimulation of forskolin-stimulated cAMP production, phosphorylation of
      extracellular signal-regulated kinases (ERK), and beta-arrestin recruitment. We
      also investigated the effect of these allosteric modulators on CB(1) agonist
      binding kinetics. Both compounds display ligand dependence, being significantly
      more potent as modulators of CP55940 signaling as compared with WIN55212 and
      having little effect on [(3)H]WIN55212 binding. Org 27569 displays biased
      antagonism whereby it inhibits: agonist-induced guanosine 5'-O-(3
      [(35)S]thio)triphosphate ([(35)S]GTPgammaS) binding, simulation (Galpha(s)
      mediated), and inhibition (Galpha(i)-mediated) of cAMP production and beta
      arrestin recruitment. In contrast, it acts as an enhancer of agonist-induced ERK
      phosphorylation. Alone, the compound can act also as an allosteric agonist,
      increasing cAMP production and ERK phosphorylation. We find that in both
      saturation and kinetic-binding experiments, the Org 27569 and PSNCBAM-1 appeared
      to influence only orthosteric ligand maximum occupancy rather than affinity. The
      data indicate that the allosteric modulators share a common mechanism whereby
      they increase available high-affinity CB(1) agonist binding sites. The receptor
      conformation stabilized by the allosterics appears to induce signaling and also
      selectively traffics orthosteric agonist signaling via the ERK phosphorylation
      pathway.

PMID- 23160941
TI  - Functional characterization of three mouse formyl peptide receptors.
AB  - The evolutionary relationship and functional correlation between human formyl
      peptide receptors (FPRs) and their mouse counterparts remain incompletely
      understood. We examined three members of the mouse formyl peptide receptor
      subfamily (mFprs) and found that they differ in agonist preference and cellular
      distributions. When stably expressed in transfected rat basophilic leukemia (RBL
      2H3) cells, mFpr1 was readily activated by N-formylated peptides derived from
      Listeria monocytogenes (fMIVTLF), Staphylococcus aureus (fMIFL), and mitochondria
      (fMMYALF). In contrast, the Escherichia coli-derived fMLF was 1000-fold less
      potent. The aforementioned peptides were much less efficacious at mFpr2, which
      responded better to the synthetic hexapeptide WKYMVm, the synthetic agonists Quin
      C1 (a substituted quinazolinone), and compound 43 (a nitrosylated pyrazolone
      derivative). Saturation binding assays showed that mFpr1 and mFpr2 were expressed
      at similar levels on the cell surface, although their affinity for N-formyl-Met
      Leu-Phe-Ile-Ile-Lys-fluorescein isothiocyanate varied by more than 1000-fold
      [dissociation constant (K(d)) values of 2.8 nM for mFpr1 and 4.8 MUM for mFpr2]).
      Contrary to these receptors, mFpr-rs1 responded poorly to all the previously
      mentioned peptides that were tested. Fluorescent microscopy revealed an
      intracellular distribution pattern of mFpr-rs1. On the basis of these results, we
      conclude that mFpr1 is an ortholog of human FPR1 with certain pharmacologic
      properties of human FPR2/ALX, whereas mFpr2 has much lower affinity for formyl
      peptides. The intracellular distribution of mFpr-rs1 suggests an evolutionary
      correlation with human FPR3.

PMID- 23160939
TI  - Risk of serious cardiovascular problems with medications for attention-deficit
      hyperactivity disorder.
AB  - Attention-deficit hyperactivity disorder (ADHD) is a chronic neurodevelopmental
      disorder characterized by persistent symptoms of inattention, hyperactivity
      and/or impulsivity. The proportion of patients diagnosed with ADHD receiving
      pharmacological treatments has increased enormously in recent years. Despite the
      well established efficacy and the good safety and tolerability profile, there is
      concern about the potential for rare but serious cardiovascular adverse events,
      as well as sudden cardiac death, with pharmacotherapies used for treating ADHD in
      children, adolescents and adults. The present paper aims to comprehensively and
      critically review the published evidence on the controversial association between
      medications approved for treating patients with ADHD and the risk of serious
      cardiovascular problems, specifically the risk of corrected QT interval (QTc)
      prolongation, and the risk of sudden cardiac death. A comprehensive search of
      relevant databases (PubMed, EMBASE and PsychINFO) was conducted to identify
      studies published in peer-reviewed journals until 21 July 2012. Clinical reports,
      as well as retrospective or prospective population-based studies with children,
      adolescents or adults as participants, of pharmacotherapies for ADHD reporting
      cardiovascular adverse events were included. Stimulant medications for ADHD,
      including methylphenidate and amphetamine derivatives, are generally safe and
      well tolerated. Small but statistically significant increases in blood pressure
      (BP) and heart rate (HR) are among the adverse events of stimulant treatment in
      all age groups. Similarly, the non-stimulant medication atomoxetine has also been
      associated with increased HR and BP, although as is the case with stimulants,
      these are generally minor, time limited and of minor clinical significance in
      children, adolescents or adults. Growing evidence suggests that these medications
      do not cause sudden and unexpected cardiac death or serious cardiovascular
      problems including statistically or clinically significant increases in QTc, at
      therapeutic doses in ADHD patients across the lifespan. Small decreases in mean
      systolic BP, diastolic BP and HR have been observed in studies with guanfacine
      extended release (-XR) or clonidine-XR, two alpha(2)-adrenergic receptor
      agonists, administered alone or in combination with psychostimulants to children
      and adolescents with ADHD. There are also no statistically or clinically
      significant increases in QTc associated with clonidine or guanfacine. There are
      no reports of torsades de pointes clearly and directly related to medications
      used for treating ADHD in patients of all age groups. The risk for serious
      cardiovascular adverse events, including statistically or clinically significant
      increases in QTc, and sudden cardiac death associated with stimulants,
      atomoxetine or alpha(2)-adrenergic agonists prescribed for ADHD is extremely low
      and the benefits of treating individual patients with ADHD, after an adequate
      assessment, outweigh the risks. However, great caution is advised when
      considering stimulant and non-stimulant medications for patients of any age with
      a diagnosis of ADHD and a personal or family history or other known risk factors
      for cardiovascular disease.

PMID- 23160942
TI  - Determination of the optimal cell-penetrating peptide sequence for intestinal
      insulin delivery based on molecular orbital analysis with self-organizing maps.
AB  - Our recent work has shown that the intestinal absorption of insulin can be
      improved significantly by coadministration of cell-penetrating peptides (CPPs),
      especially penetratin. However, a relatively high dose of penetratin is required
      to adequately stimulate the intestinal absorption of insulin. Therefore, in this
      study, we sought to determine the CPP that most effectively enhanced intestinal
      insulin absorption. An in situ loop absorption study using 26 penetratin
      analogues suggested that the chain length, hydrophobicity, and amphipathicity of
      the CPPs, as well as their basicity, contribute to their absorption-enhancing
      efficiency. Moreover, a molecular orbital method with self-organizing maps (SOMs)
      classification suggested that multiple factors, including the molecular weight,
      basicity, the lowest unoccupied molecular orbital energy, absolute hardness, and
      chemical potential of CPPs, are associated with their effects on intestinal
      insulin absorption. Furthermore, the new CPPs proposed by SOM clustering had a
      marked capacity to interact with insulin, and their ability to enhance insulin
      absorption was much stronger than that of the original penetratin. Therefore, the
      peptide sequence that optimally enhances intestinal insulin absorption could be
      defined by SOM with the molecular orbital method, and our present work emphasizes
      the utility of such methodologies in the development of effective drug delivery
      systems.

PMID- 23160943
TI  - Overwintering strategy of Yunnan snub-nosed monkeys: adjustments in activity
      scheduling and foraging patterns.
AB  - Temperate forests are characterized by pronounced climatic and phenological
      seasonality. Primates inhabiting such environments experience prolonged resource
      scarcity and low ambient temperatures in winter and are expected to adjust time
      allocation and foraging behavior so as to maintain their energy balance. We
      analyzed the activity scheduling of a group of Yunnan snub-nosed monkeys
      (Rhinopithecus bieti) based on data collected over 20 months in the high-altitude
      (>3000 m) Samage Forest, Baimaxueshan Nature Reserve, PRC. The forest consists of
      evergreen conifers and oaks and deciduous broadleaf trees. The diet varied
      seasonally, with young leaves preferentially exploited in spring and fruits in
      summer. The monkeys subsisted on readily available fallback resources (mainly
      lichens) in winter [Grueter et al. in (Am J Phys Anthropol 140:700-715, 2009)].
      We predicted that this switch to a relatively low-quality diet would prompt an
      increase in feeding effort and decrease in moving effort. We found that the
      monkeys spent significantly more time feeding in winter than in the other
      seasons. The monthly time devoted to feeding was also negatively correlated with
      temperature and positively with percentage of lichens in the diet. Time spent on
      moving did not vary among seasons or with temperature, but day-journey length was
      found to be longer on hotter days. Time spent resting was lower in winter and
      under colder conditions and was also negatively correlated with time spent
      feeding, indicating that resting time is converted into feeding time during times
      of ecological stress. These results indicate a strong effect of seasonality on
      time allocation patterns, constraints on inactivity phases, and the prevalence of
      an energy-conserving foraging strategy in winter, when costs of thermoregulation
      were high and the availability of preferred food was low.

PMID- 23160944
TI  - Identification of individual adult female Javan lutungs (Trachypithecus auratus
      sondaicus) by using patterns of dark pigmentation in the pubic area.
AB  - In a series of field surveys of wild Javan lutungs (Trachypithecus auratus
      sondaicus) conducted at Pangandaran Nature Reserve in West Java, Indonesia, from
      2011 to 2012, we tried to use a method of individual identification by using
      individual-specific patterns of dark pigmentation in the pubic area. During the
      2011 dry season, we used a digital SLR camera with a 400-mm telephoto lens to
      photograph the pubic area of each individual of a habituated group. These
      photographs were the basis for identifying 14 different adult females. During the
      rainy season of 2011 and the dry season of 2012, we checked the presence/absence
      of each of the identified individuals and found that these patterns were stable,
      at least during our study period. We found that two adult females and one adult
      female disappeared from the subject group between the first and second and
      between the second and third surveys, respectively, and that one adult female
      gave birth between the first and second surveys, but the infant had disappeared
      from the group between the second and third surveys. We could not confirm the
      validity of the method for juvenile females because of the dense white hair in
      their pubic areas and the fact that few individuals had clear patterns.
      Furthermore, we could not use this method for males because of the lack of
      pigmentation in the pubic area. As patterns of pigmentation in the pubic area are
      known to be present in other Trachypithecus species, our method can be useful for
      identification of individual adult females of these species, on which few
      individual-based behavioral studies have been conducted. Collecting individual
      based behavioral data would enable us to track the presence of individuals in
      groups or movements between groups; determine the effects of social rank and age
      on within-group competition and copulation; and examine population data.

PMID- 23160945
TI  - Smoking, variation in N-acetyltransferase 1 (NAT1) and 2 (NAT2), and risk of non
      Hodgkin lymphoma: a pooled analysis within the InterLymph consortium.
AB  - PURPOSE: Studies of smoking and risk of non-Hodgkin lymphoma (NHL) have yielded
      inconsistent results, possibly due to subtype heterogeneity and/or genetic
      variation impacting the metabolism of tobacco-derived carcinogens, including
      substrates of the N-acetyltransferase enzymes NAT1 and NAT2. METHODS: We
      conducted a pooled analysis of 5,026 NHL cases and 4,630 controls from seven case
      control studies in the international lymphoma epidemiology consortium to examine
      associations between smoking, variation in the N-acetyltransferase genes NAT1 and
      NAT2, and risk of NHL subtypes. Smoking data were harmonized across studies, and
      genetic variants in NAT1 and NAT2 were used to infer acetylation phenotype of the
      NAT1 and NAT2 enzymes, respectively. Pooled odds ratios (ORs) and 95 % confidence
      intervals (95 % CIs) for risk of NHL and subtypes were calculated using joint
      fixed effects unconditional logistic regression models. RESULTS: Current smoking
      was associated with a significant 30 % increased risk of follicular lymphoma (n =
      1,176) but not NHL overall or other NHL subtypes. The association was similar
      among NAT2 slow (OR 1.36; 95 % CI 1.07-1.75) and intermediate/rapid (OR 1.27; 95
      % CI 0.95-1.69) acetylators (p (interaction) = 0.82) and also did not differ by
      NAT1*10 allelotype. Neither NAT2 phenotype nor NAT1*10 allelotype was associated
      with risk of NHL overall or NHL subtypes. CONCLUSION: The current findings
      provide further evidence for a modest association between current smoking and
      follicular lymphoma risk and suggest that this association may not be influenced
      by variation in the N-acetyltransferase enzymes.

PMID- 23160946
TI  - Anemia control in renal transplant recipients receiving continuous erythropoietin
      receptor activator (C.E.R.A.) treatment: the AnemiaTrans Study.
AB  - INTRODUCTION: Continuous erythropoietin receptor activator (C.E.R.A.) effectively
      enables anemia control in patients with chronic kidney disease, but little
      information is available in renal transplant recipients. The authors aimed to
      evaluate the effect of C.E.R.A. under clinical practice conditions on anemia
      control in renal transplant recipients. METHODS: This was a multicenter,
      retrospective, observational study carried out in adult renal transplant patients
      in the immediate posttransplant period and at late posttransplant period
      receiving C.E.R.A. in clinical practice. Patients' data were retrieved from their
      medical charts at baseline and months 1, 3, and 6. RESULTS: A total of 318
      evaluable patients were enrolled into the study: 32 in the immediate
      posttransplant period and 286 at late posttransplant period (erythropoiesis
      stimulating agent [ESA]-naive, n = 44; converting from other ESAs, n = 242).
      Patients in the immediate posttransplant period experienced a significant
      increase in hemoglobin (Hb) levels from baseline to month 1 (9.9+/-1.5 g/dL vs.
      11.5+/-1.4 g/dL; P< 0.001). ESA-naive patients showed increasing mean Hb levels
      from baseline to month 6 (10.1+/-0.7 g/dL vs. 11.7+/-1.0 g/dL; P < 0.001) and
      94.7% achieved Hb >=11 g/dL during the study. In patients converted from other
      ESAs, the percentage of patients with Hb between 11-13 g/dL was maintained from
      baseline to month 6 with no significant differences (61.0% vs. 62.4%). Mean
      monthly doses of C.E.R.A. at baseline were 134.4+/-56.4 MUg, 81.3+/-28.1 MUg, and
      93.0+/-44.2 MUg in immediate posttransplant, ESA-naive, and converted patients,
      respectively. C.E.R.A. was well tolerated. CONCLUSION: C.E.R.A. enables anemia
      control in renal transplant recipients, allowing target Hb levels to be achieved
      and maintained with doses even below those described in the Summary of Product
      Characteristics.

PMID- 23160947
TI  - Overexpression of the formaldehyde dehydrogenase gene from Brevibacillus brevis
      to enhance formaldehyde tolerance and detoxification of tobacco.
AB  - The faldh gene coding for a putative Brevibacillus brevis formaldehyde
      dehydrogenase (FALDH) was isolated and then transformed into tobacco. A total of
      three lines of transgenic plants were generated, with each showing 2- to 3-fold
      higher specific formaldehyde dehydrogenase activities than wild-type tobacco, a
      result that demonstrates the functional activity of the enzyme in formaldehyde
      (HCHO) oxidation. Overexpression of faldh in tobacco confers a high tolerance to
      exogenous HCHO and an increased ability to take up HCHO. A (13)C-nuclear magnetic
      resonance technique revealed that the transgenic plants were able to oxidize more
      aqueous HCHO to formate than the wild-type (WT) plants. When treated with gaseous
      HCHO, the transgenic tobacco exhibited an enhanced ability to transform more HCHO
      into formate, citrate acid, and malate but less glycine than the WT plants. These
      results indicate that the increased capacity of the transgenic tobacco to take
      up, tolerate, and metabolize higher concentrations of HCHO was due to the
      overexpression of B. brevis FALDH, revealing the essential function of this
      enzyme in HCHO detoxification. Our results provide a potential genetic
      engineering strategy for improving the phytoremediation of HCHO pollution.

PMID- 23160948
TI  - Kinetics and computational docking studies on the inhibition of tyrosinase
      induced by oxymatrine.
AB  - A combination of enzymatic inhibition kinetics and computational prediction was
      employed to search for an effective inhibitor of tyrosinase. We found that
      oxymatrine significantly inhibited tyrosinase, and that this reaction was not
      accompanied by detectable conformational changes. Kinetic analysis showed that
      oxymatrine reversibly inhibited tyrosinase in a mixed-type manner. Measurements
      of intrinsic and ANS-binding fluorescences showed that oxymatrine did not induce
      any conspicuous changes in the tertiary structure. We also conducted a docking
      simulation between tyrosinase and oxymatrine using two docking programs, Dock6.3
      and AutoDock4.2 (binding energy was -118.81 kcal/mol for Dock6 and -8.04 kcal/mol
      for AutoDock4). The results also suggested that oxymatrine interacts mostly with
      the residues of CYS83 and HIS263 in the active site of tyrosinase. This strategy
      of predicting tyrosinase inhibition by simulation of docking coupling with
      kinetics may prove useful in screening for potential tyrosinase inhibitors.
      Knowledge of tyrosinase inhibition can provide medical, cosmetic, and
      agricultural applications. Our study suggests that oxymatrine is an important
      agent for various applications related to pigment formation.

PMID- 23160949
TI  - Recombinant single-chain antibody with the Trojan peptide penetratin positioned
      in the linker region enables cargo transfer across the blood-brain barrier.
AB  - Delivery of therapeutic proteins into tissues and across the blood-brain barrier
      (BBB) is limited by the size and biochemical properties of the proteins.
      Efficient delivery across BBB is generally restricted to small, highly lipophilic
      molecules. However, in the last decades, several peptides that can pass cell
      membranes have been identified. It has been shown that these peptides are also
      capable of delivering large hydrophilic cargoes into cells and are therefore a
      powerful biological tool for transporting drugs across cell membranes and even
      into the brain. We designed and prepared a single-chain antibody fragment
      (scFvs), specific for the pathological form of the prion protein (PrP(Sc)), where
      a cell-penetrating peptide (CPP) was used as a linker between the two variable
      domains of the scFv. The intravenously administered recombinant scFv-CPP was
      successfully targeted to and delivered into mouse brain cells. Our single-chain
      antibody fragments are of special interest in view of possible therapeutic
      reagents design not only for prion diseases but also for other neurodegenerative
      diseases.

PMID- 23160950
TI  - Self-control and its relation to emotions and psychobiology: evidence from a Day
      Reconstruction Method study.
AB  - This study aimed to ascertain whether self-control predicts heart rate, heart
      rate variability, and the cortisol slope, and to determine whether health
      behaviors and affect patterns mediate these relationships. A sample of 198 adults
      completed the Self-Control Scale (Tangney in J Pers 72:271-322, 2004), and
      reported their exercise levels, and cigarette and alcohol use. Participants
      provided a complete account of their emotional experiences over a full day, along
      with morning and evening salivary cortisol samples and a continuous measure of
      cardiovascular activity on the same day. High trait self-control predicted low
      resting heart rate, high heart rate variability, and a steep cortisol slope.
      Those with high self-control displayed stable emotional patterns which explained
      the link between self-control and the cortisol slope. The self-controlled smoked
      less and this explained their low heart rates. The capacity to sustain stable
      patterns of affect across diverse contexts may be an important pathway through
      which self-control relates to psychophysiological functioning and potentially
      health. 

PMID- 23160951
TI  - Use of proteomic methods in the analysis of human body fluids in Alzheimer
      research.
AB  - Proteomics is the study of the entire population of proteins and peptides in an
      organism or a part of it, such as a cell, tissue, or fluids like cerebrospinal
      fluid, plasma, serum, urine, or saliva. It is widely assumed that changes in the
      composition of the proteome may reflect disease states and provide clues to its
      origin, eventually leading to targets for new treatments. The ability to perform
      large-scale proteomic studies now is based jointly on recent advances in our
      analytical methods. Separation techniques like CE and 2DE have developed and
      matured. Detection methods like MS have also improved greatly in the last 5
      years. These developments have also driven the fields of bioinformatics, needed
      to deal with the increased data production and systems biology. All these
      developing methods offer specific advantages but also come with certain
      limitations. This review describes the different proteomic methods used in the
      field, their limitations, and their possible pitfalls. Based on a literature
      search in PubMed, we identified 112 studies that applied proteomic techniques to
      identify biomarkers for Alzheimer disease. This review describes the results of
      these studies on proteome changes in human body fluids of Alzheimer patients
      reviewing the most important studies. We extracted a list of 366 proteins and
      peptides that were identified by these studies as potential targets in Alzheimer
      research.

PMID- 23160952
TI  - Severe acute hepatitis B in a treatment-naive patient with antiviral drug
      resistant mutations in the polymerase gene.
AB  - This is a case of 62 years old Caucasian treatment-naive patient who developed a
      severe acute hepatitis B infection soon after a trip to Thailand. The infection
      was due to genotype C HBV which was found to be resistant to lamivudine and
      telbivudine. The patient was treated with tenofovir resulting in complete
      suppression of viral replication and complete clinical and laboratory remission
      of acute hepatitis. Later the patient also developed seroconversion of HBeAg to
      anti-HBe and of HBsAg to anti-HBs. This case demonstrates that mutations of HBV
      polymerase associated with lamivudine, telbivudine, and adefovir resistance can
      be present also in untreated patients with severe acute hepatitis B. This
      suggests that in the clinical context, which represents a life threatening
      condition, a baseline resistance-testing should be an additional marker in the
      diagnostic evaluation process. Finally, this case report seems to support the use
      of tenofovir for the immediate treatment of severe acute hepatitis B.

PMID- 23160953
TI  - The COMPASS subunit Spp1 links histone methylation to initiation of meiotic
      recombination.
AB  - During meiosis, combinatorial associations of genetic traits arise from
      homologous recombination between parental chromosomes. Histone H3 lysine 4
      trimethylation marks meiotic recombination hotspots in yeast and mammals, but how
      this ubiquitous chromatin modification relates to the initiation of double-strand
      breaks (DSBs) dependent on Spo11 remains unknown. Here, we show that the
      tethering of a PHD-containing protein, Spp1 (a component of the COMPASS complex),
      to recombinationally cold regions is sufficient to induce DSB formation.
      Furthermore, we found that Spp1 physically interacts with Mer2, a key protein of
      the differentiated chromosomal axis required for DSB formation. Thus, by
      interacting with H3K4me3 and Mer2, Spp1 promotes recruitment of potential meiotic
      DSB sites to the chromosomal axis, allowing Spo11 cleavage at nearby nucleosome
      depleted regions.

PMID- 23160954
TI  - C/EBP transcription factors mediate epicardial activation during heart
      development and injury.
AB  - The epicardium encapsulates the heart and functions as a source of multipotent
      progenitor cells and paracrine factors essential for cardiac development and
      repair. Injury of the adult heart results in reactivation of a developmental gene
      program in the epicardium, but the transcriptional basis of epicardial gene
      expression has not been delineated. We established a mouse embryonic heart organ
      culture and gene expression system that facilitated the identification of
      epicardial enhancers activated during heart development and injury. Epicardial
      activation of these enhancers depends on a combinatorial transcriptional code
      centered on CCAAT/enhancer binding protein (C/EBP) transcription factors.
      Disruption of C/EBP signaling in the adult epicardium reduced injury-induced
      neutrophil infiltration and improved cardiac function. These findings reveal a
      transcriptional basis for epicardial activation and heart injury, providing a
      platform for enhancing cardiac regeneration.

PMID- 23160956
TI  - Optomechanical dark mode.
AB  - Thermal mechanical motion hinders the use of a mechanical system in applications
      such as quantum information processing. Whereas the thermal motion can be
      overcome by cooling a mechanical oscillator to its motional ground state, an
      alternative approach is to exploit the use of a mechanically dark mode that can
      protect the system from mechanical dissipation. We have realized such a dark mode
      by coupling two optical modes in a silica resonator to one of its mechanical
      breathing modes in the regime of weak optomechanical coupling. The dark mode,
      which is a superposition of the two optical modes and is decoupled from the
      mechanical oscillator, can still mediate an effective optomechanical coupling
      between the two optical modes. We show that the formation of the dark mode
      enables the transfer of optical fields between the two optical modes.
      Optomechanical dark mode opens the possibility of using mechanically mediated
      coupling in quantum applications without cooling the mechanical oscillator to its
      motional ground state.

PMID- 23160957
TI  - Porphyry-copper ore shells form at stable pressure-temperature fronts within
      dynamic fluid plumes.
AB  - Porphyry-type ore deposits are major resources of copper and gold, precipitated
      from fluids expelled by crustal magma chambers. The metals are typically
      concentrated in confined ore shells within vertically extensive vein networks,
      formed through hydraulic fracturing of rock by ascending fluids. Numerical
      modeling shows that dynamic permeability responses to magmatic fluid expulsion
      can stabilize a front of metal precipitation at the boundary between
      lithostatically pressured up-flow of hot magmatic fluids and hydrostatically
      pressured convection of cooler meteoric fluids. The balance between focused heat
      advection and lateral cooling controls the most important economic
      characteristics, including size, shape, and ore grade. This self-sustaining
      process may extend to epithermal gold deposits, venting at active volcanoes, and
      regions with the potential for geothermal energy production.

PMID- 23160958
TI  - Alignment of magnetized accretion disks and relativistic jets with spinning black
      holes.
AB  - Accreting black holes (BHs) produce intense radiation and powerful relativistic
      jets, which are affected by the BH's spin magnitude and direction. Although thin
      disks might align with the BH spin axis via the Bardeen-Petterson effect, this
      does not apply to jet systems with thick disks. We used fully three-dimensional
      general relativistic magnetohydrodynamical simulations to study accreting BHs
      with various spin vectors and disk thicknesses and with magnetic flux reaching
      saturation. Our simulations reveal a "magneto-spin alignment" mechanism that
      causes magnetized disks and jets to align with the BH spin near BHs and to
      reorient with the outer disk farther away. This mechanism has implications for
      the evolution of BH mass and spin, BH feedback on host galaxies, and resolved BH
      images for the accreting BHs in SgrA* and M87.

PMID- 23160955
TI  - Multiplex targeted sequencing identifies recurrently mutated genes in autism
      spectrum disorders.
AB  - Exome sequencing studies of autism spectrum disorders (ASDs) have identified many
      de novo mutations but few recurrently disrupted genes. We therefore developed a
      modified molecular inversion probe method enabling ultra-low-cost candidate gene
      resequencing in very large cohorts. To demonstrate the power of this approach, we
      captured and sequenced 44 candidate genes in 2446 ASD probands. We discovered 27
      de novo events in 16 genes, 59% of which are predicted to truncate proteins or
      disrupt splicing. We estimate that recurrent disruptive mutations in six genes
      CHD8, DYRK1A, GRIN2B, TBR1, PTEN, and TBL1XR1-may contribute to 1% of sporadic
      ASDs. Our data support associations between specific genes and reciprocal
      subphenotypes (CHD8-macrocephaly and DYRK1A-microcephaly) and replicate the
      importance of a beta-catenin-chromatin-remodeling network to ASD etiology.

PMID- 23160959
TI  - Sousse, Tunisia: tumultuous history and high Y-STR diversity.
AB  - In the present study, 17 Y-chromosomal STR (Y-STR) loci were typed in 218
      unrelated males from Sousse, Central-East Tunisia, to evaluate forensic and
      population genetic applications of the data. A total of 154 different haplotypes
      were identified, 127 (82.5%) of which were unique, with the most frequent
      haplotype occurring in 14 individuals (6.4%). The locus diversity ranged from
      0.2050 at DYS392 to 0.8760 at DYS385. The haplotype diversity at the 17-loci
      resolution was calculated to be 0.9916, while the corresponding values for the
      extended (11 loci) and minimal (9 loci) haplotypes were estimated at 0.9735 and
      0.9710, respectively. Comparison with 29 regional and global populations using
      correspondence analysis, neighbor joining (NJ) tree, and Rst genetic distance
      revealed that the Sousse population is highly diverse. This finding is consistent
      with historical data. Furthermore, the results of this study indicate a distinct
      genetic substructure among Tunisian populations. In conclusion, the present study
      demonstrated that the 17 Y-STRs analyzed are highly informative for individual
      identification, parentage analysis, and population genetic studies.

PMID- 23160961
TI  - Plasma ghrelin is positively associated with body fat, liver fat and milk fat
      content but not with feed intake of dairy cows after parturition.
AB  - Ghrelin is a gastrointestinal peptide hormone that is present in blood mostly in
      a non-posttranslationally modified form, with a minor proportion acylated at
      Ser(3). Both ghrelin forms were initially assigned a role in the control of food
      intake but there is accumulating evidence for their involvement in fat allocation
      and utilization. We investigated changes in the ghrelin system in dairy cows,
      exhibiting differences in body fat mobilization and fatty liver, from late
      pregnancy to early lactation. Sixteen dairy cows underwent liver biopsy and were
      retrospectively grouped based on high (H) or low (L) liver fat content post
      partum. Both groups had a comparable feed intake in week -6 (before parturition)
      and week 2 (after parturition). Only before parturition was preprandial total
      ghrelin concentration higher in L than in H cows and only after parturition was
      the basal plasma concentration of non-esterified fatty acids higher in H than in
      L cows. Both before and after parturition, H cows had higher preprandial plasma
      concentrations of acyl ghrelin, a higher acyl:total ghrelin ratio, lower plasma
      triacylglyceride concentrations and a lower respiratory quotient compared with L
      cows. These group differences could not be attributed to an allelic variant of
      the acyl ghrelin receptor. Rather, the ratio of acyl:total ghrelin correlated
      with several aspects of fat metabolism and with respiratory quotient but not with
      feed intake. These results show that endogenous ghrelin forms are associated with
      fat allocation, fatty liver, and utilization of fat during the periparturient
      period.

PMID- 23160960
TI  - Understanding gender differences in statin use among elderly Medicare
      beneficiaries: an application of decomposition technique.
AB  - BACKGROUND: Pharmacotherapy with statins (HMG-CoA reductase inhibitors) is the
      cornerstone for lipid management in individuals with or at risk of developing
      cardiovascular diseases. Although the clinical benefits of statins are
      established for both women and men, there is evidence of a gender difference in
      their use. The current study extends prior scientific research by estimating the
      extent to which individual-level variables may explain gender differences in
      statin use by using a post-regression non-linear decomposition technique.
      OBJECTIVE: The objective of this study was to estimate the magnitude of gender
      differences in statin use among the elderly and examine individual-level
      variables that can explain the gender differences in statin use among elderly
      individuals with or at risk of cardiovascular diseases. METHODS: A retrospective
      cross-sectional study design was adopted. Data were derived from the 2005
      Medicare Current Beneficiary Survey (MCBS), a nationally representative survey of
      Medicare beneficiaries in the US. The analytic study sample consisted of
      community-dwelling elderly Medicare beneficiaries, aged 65 years or older, who
      had reported any of the following conditions: heart disease, hyperlipidaemia or
      diabetes mellitus, and who were alive during the observation year. Chi-square
      tests were used to evaluate the unadjusted associations between gender and statin
      use for each of the characteristics. Multivariate logistic regressions were used
      to evaluate the relationship between gender and statin use. A post-regression non
      linear decomposition approach was used to understand individual-level variables
      that could explain gender differences in statin use. RESULTS: Among 5,508
      elderly, 47.2% of the women and 55.5% of the men reported any statin use in 2005,
      which translates to an 8.3 percentage point difference in statin use. In the
      multivariate logistic regression on statin use, women were 21% less likely than
      men to use statins (adjusted odds ratio = 0.79; 95% CI 0.69, 0.89). Post
      regression non-linear decomposition analysis revealed that of the 8.3 percentage
      point difference in statin use, 29.5% was explained by the individual-level
      variables. Lifestyle risk factors accounted for most of the explained portion of
      the gender difference in statin use. CONCLUSIONS: Among elderly Medicare
      beneficiaries, women were less likely than men to report any use of statins. Less
      than one third of the total gender difference in statin use was attributed to
      individual-level variables such as demographics, economic status, physical health
      status, depression and lifestyle risk factors. Further research is needed to
      identify whether provider and/or organizational-level factors can further explain
      the gender difference in statin use.

PMID- 23160962
TI  - Involvement of the Ca2+-responsive transactivator in high glucose-induced beta
      cell apoptosis.
AB  - The calcium-regulated transcription coactivator, Ca(2)(+)-responsive
      transactivator (CREST) was expressed in pancreatic beta-cells. Moreover, CREST
      expression became significantly increased in pancreatic islets isolated from
      hyperglycemic Goto-Kakizaki rats compared with normoglycemic Wistar controls. In
      addition, culture of beta-cells in the presence of high glucose concentrations
      also increased CREST expression in vitro. To further investigate the role of this
      transactivator in the regulation of beta-cell function, we established a stable
      beta-cell line with inducible CREST expression. Hence, CREST overexpression
      mimicked the glucotoxic effects on insulin secretion and cell growth in beta
      cells. Moreover, high glucose-induced apoptosis was aggravated by upregulation of
      the transactivator but inhibited when CREST expression was partially silenced by
      siRNA technology. Further investigation found that upregulation of Bax and
      downregulation of Bcl2 was indeed induced by its expression, especially under
      high glucose conditions. In addition, as two causing factors leading to beta-cell
      apoptosis under diabetic conditions, endoplasmic reticulum stress and high free
      fatty acid, mimicked the high glucose effects on CREST upregulation and
      generation of apoptosis in beta-cells, and these effects were specifically offset
      by the siRNA knockdown of CREST. These results indicated that CREST is implicated
      in beta-cell apoptosis induced by culture in high glucose and hence that CREST
      may become a potential pharmacological target for the prevention and treatment of
      type 2 diabetes mellitus.

PMID- 23160963
TI  - In utero and lactational exposure to vinclozolin and genistein induces genomic
      changes in the rat mammary gland.
AB  - Exposure to low doses of environmental estrogens such as bisphenol A and
      genistein (G) alters mammary gland development. The effects of environmental anti
      androgens, such as the fungicide vinclozolin (V), on mammary gland morphogenesis
      are unknown. We previously reported that perinatal exposure to G, V, and the GV
      combination causes histological changes in the mammary gland during the
      peripubertal period, suggesting alterations to the peripubertal hormone response.
      We now investigate whether perinatal exposure to these compounds alters the gene
      expression profiles of the developing glands to identify the dysregulated
      signaling pathways and the underlying mechanisms. G, V, or GV (1 mg/kg body
      weight per day) was added to diet of Wistar rats, from conception to weaning;
      female offspring mammary glands were collected at postnatal days (PNDs) 35 and
      50. Genes displaying differential expression and belonging to different
      functional categories were validated by quantitative PCR and immunocytochemistry.
      At PND35, G had little effect; the slight changes noted were in genes related to
      morphogenesis. The changes following exposure to V concerned the functional
      categories associated with development (Cldn1, Krt17, and Sprr1a), carbohydrate
      metabolism, and steroidogenesis. The GV mixture upregulated genes (Krt17, Pvalb,
      and Tnni2) involved in muscle development, indicating effects on myoepithelial
      cells during mammary gland morphogenesis. Importantly, at PND50, cycling females
      exposed to GV showed an increase in the expression of genes (Csn2, Wap, and Elf5)
      related to differentiation, consistent with the previously reported abnormal
      lobuloalveolar development previously described. Thus, perinatal exposure to GV
      alters the mammary gland hormone response differently at PND35 (puberty) and in
      animals with established cycles.

PMID- 23160964
TI  - 1,25-Dihydroxyvitamin D3 upregulates leptin expression in mouse adipose tissue.
AB  - Leptin is an adipose tissue-derived hormone that plays a critical role in energy
      homeostasis. Vitamin D has been shown to regulate energy metabolism, but the
      relationship between vitamin D and leptin is unclear. Leptin expression and
      secretion was reduced in vitamin D receptor (VDR)-null mice and increased in
      transgenic (Tg) mice overexpressing the VDR in adipocytes; however, as leptin is
      mainly determined by fat mass, it is unclear whether the vitamin D hormone
      directly regulates leptin expression. To address this question, we determined the
      effect of vitamin D on leptin expression in vivo and ex vivo. One-week treatment
      of WT mice with the vitamin D analog RO-27-5646 led to a significant increase in
      adipose leptin mRNA transcript and serum leptin levels. Moreover, in adipose
      tissue cultures, 1,25-dihydroxyvitamin D markedly stimulated mRNA expression and
      secretion of leptin, but not resistin, in adipose tissues obtained from WT mice,
      but not from VDR-null mice, and leptin upregulation induced by 1,25
      dihydroxyvitamin D was more robust in adipose tissues obtained from VDR Tg mice
      compared with WT mice. These data demonstrate that 1,25-dihydroxyvitamin D
      stimulates adipose leptin production in a VDR-dependent manner, suggesting that
      vitamin D may affect energy homeostasis through direct regulation of leptin
      expression.

PMID- 23160965
TI  - Of fat mice and men: the rise of the adipokines.

PMID- 23160966
TI  - Adipokine inflammation and insulin resistance: the role of glucose, lipids and
      endotoxin.
AB  - Adipose tissue is an active endocrine organ, and our knowledge of this secretory
      tissue, in recent years, has led us to completely rethink how our body functions
      and becomes dysregulated with weight gain. Human adipose tissue appears to act as
      a multifunctional secretory organ with the capacity to control energy
      homoeostasis through peripheral and central regulation of energy homoeostasis. It
      also plays an important role in innate immunity. However, the capability to more
      than double its original mass to cope with positive energy balance in obesity
      leads to many pathogenic changes. These changes arise within the adipose tissue
      as well as inducing secondary detrimental effects on other organs like muscle and
      liver, including chronic low-grade inflammation mediated by adipocytokines
      (adipokine inflammation). This inflammation is modulated by dietary factors and
      nutrients including glucose and lipids, as well as gut bacteria in the form of
      endotoxin or LPS. The aim of this current review is to consider the impact of
      nutrients such as glucose and lipids on inflammatory pathways, specifically
      within adipose tissue. Furthermore, how nutrients such as these can influence
      adipokine inflammation and consequently insulin resistance directly through their
      effects on secretion of adipocytokines (TNFalpha, IL6 and resistin) as well as
      indirectly through increases in endotoxin is discussed.

PMID- 23160967
TI  - Role of adipokines in cardiovascular disease.
AB  - The discovery of leptin in 1994 sparked dramatic new interest in the study of
      white adipose tissue. It is now recognised to be a metabolically active endocrine
      organ, producing important chemical messengers - adipokines and cytokines
      (adipocytokines). The search for new adipocytokines or adipokines gained added
      fervour with the prospect of the reconciliation between cardiovascular diseases
      (CVDs), obesity and metabolic syndrome. The role these new chemical messengers
      play in inflammation, satiety, metabolism and cardiac function has paved the way
      for new research and theories examining the effects they have on (in this case)
      CVD. Adipokines are involved in a 'good-bad', yin-yang homoeostatic balance
      whereby there are substantial benefits: cardioprotection, promoting endothelial
      function, angiogenesis and reducing hypertension, atherosclerosis and
      inflammation. The flip side may show contrasting, detrimental effects in
      aggravating these cardiac parameters.

PMID- 23160968
TI  - A man with a blocked nose.

PMID- 23160969
TI  - Former Bush adviser is appointed to lead Global Fund.

PMID- 23160970
TI  - Investigations begin into death of woman who was refused an abortion.

PMID- 23160971
TI  - Exploring the relationships between scaled bioequivalence limits and within
      subject variability.
AB  - Assessment of bioequivalence (BE) for highly variable drugs is challenging. As
      within-subject variability increases, it becomes more difficult to prove BE,
      unless a large number of subjects is recruited. In order to face this problem,
      several approaches have been proposed. Among them, scaled BE limits (BEL) have
      recently attracted special attention because the European Medicines Agency and
      the US Food and Drug Administration adopted scaled approaches. Scaled BELs expand
      with variability using specific mathematical functions while include additional
      regulatory criteria in some cases. The aim of this study is twofold: (1) to
      provide a deeper insight into the dependence of scaled BELs on variability and
      (2) to unveil the underlying mathematical relationships. The comparative analysis
      of these BELs is implemented through algebraic manipulations and graphic
      illustrations. Special emphasis is placed on the "absolute change" of each BEL
      and the "relative change," reflecting the portion of the relative to the maximum
      expansion of a BEL. This analysis reveals the causal differences between the
      different BELs on the mode of "absolute" and "relative" change. The results
      derived from this study are in agreement with the observed different performances
      of the various scaled BE approaches.

PMID- 23160972
TI  - Respiratory function in late-onset Pompe disease patients receiving long-term
      enzyme replacement therapy for more than 48 months.
AB  - Respiratory impairment is the most important prognostic factor in patients with
      adult-onset Pompe disease. The effect of long-term enzyme replacement therapy
      (ERT) on pulmonary function remains unclear.Respiratory parameters (vital
      capacity (VCmax); forced expiratory volume (FEV1); peak expiratory flow (PEF);
      and blood gas analysis) were monitored every 6 months during a treatment period
      of 48-77 months of ERT in six patients with genetically and biochemically
      confirmed adult-onset Pompe disease. Postural drop of VCmax from sitting to
      supine position, maximal inspiratory muscle pressure (PImax), mouth occlusion
      pressure after 100 ms (P0.1), and peak cough flow (PCF) were measured over a
      period of 12 months. Mean change to baseline were +8.8 % points for DeltaVCmax,
      +6.2 % points for DeltaFEV1, and +6.6 % points for DeltaPEF after 48 months of
      ERT. In one patient, a decrease of respiratory parameters with later
      stabilization was observed under ERT until month 42, but noninvasive ventilation
      (NIV) had to be initiated due to nocturnal desaturation. In the final 12 months
      period, progressive diaphragm weakness was detected in 3/6 patients (median
      change in VC% drop +8 %).ERT seems to stabilize pulmonary function and may delay
      the requirement for ventilation in patients with late-onset Pompe disease.

PMID- 23160974
TI  - Biomarkers.

PMID- 23160973
TI  - [Mechanisms and risk factors for type 1 food allergies: the role of gastric
      digestion].
AB  - True food allergens are considered as digestion stable proteins, which are
      absorbed through the gastrointestinal epithelium in an intact form leading to
      sensitization and causing systemic symptoms. According to classifications,
      allergens, which are digestion-labile, cause local symptoms by their cross
      reactivity towards inhalative allergens. Our recent studies revealed that
      digestion labile allergens can also have sensitizing capacity if gastric
      digestion is hindered. The increase of gastric pH via acid-suppression by proton
      pump inhibitors, sucralfate or antacids, interferes with protein digestion, and
      leads to sensitization and allergic reaction in mouse models as well as in human
      patients. Furthermore, the inhibition of digestion increases the risk for
      anaphylactic responses in sensitized individuals.Even though also other factors,
      such as sphingolipid metabolites, are associated with the development of food
      allergies, it is without any doubt that the stomach has an important gate keeping
      function against food allergies.

PMID- 23160975
TI  - [Amelanotic rectal melanoma--additional comments on the basis of a specific
      special case of Jongen et al].

PMID- 23160976
TI  - Impact of cardiac rehabilitation exercise program on left ventricular diastolic
      function in coronary artery disease: a pilot study.
AB  - Diastolic dysfunction is common in coronary artery disease (CAD). Exercise-based
      cardiac rehabilitation (CR) improves survival and quality of life but its effect
      on diastolic function is unclear. We sought to determine the impact of CR on
      diastolic function. We conducted a prospective study of CAD patients referred for
      3-month outpatient CR, with pre-CR and post-CR echocardiograms. Twenty-five
      outpatients (age [mean +/- SD], 66 +/- 11 ! years; 7 [28 %] women; 22 [88 %] with
      recent acute coronary syndrome) were recruited upon beginning CR; one patient
      lacking follow-up was excluded from analysis. Before CR, patients' mean ejection
      fraction was 61 +/- 7 %; regional wall motion score index was 1.18 +/- 0.28; and
      left ventricular diastolic dysfunction existed in 21 (88 %). Of the 24 (96 %)
      patients with post-CR follow-up, 12 (50 %) had improved diastolic function, 2 of
      the 24 (8 %) had normal diastolic function throughout, nine (38 %) remained at
      the same grade, and one (4 %) had worsened diastolic function. The E/e' ratio
      improved significantly after CR (11.9 +/- 4.5 vs. 10.7 +/- 4.5; P = .048).
      Fourteen patients with normal or improved diastolic function had a greater
      decrease in left atrial volume index (-4.2 +/- 6.3 vs. 1.6 +/- 6.3 mL/m(2); P =
      .04) and a greater increase in peak untwisting rate (20 +/- 36 vs. -42 +/- 45 
      degrees /s; P = .003) than did patients with no diastolic improvement. Three
      month, exercise-based CR was associated with improved left ventricular diastolic
      function in half of our patients. Further large studies are needed to clarify the
      effect of CR on diastolic dysfunction in patients with CAD.

PMID- 23160978
TI  - Comment to: chemical components separation with botulinum toxin A: a novel
      technique to improve primary fascial closure rates of the open abdomen by
      Zielinski et al.

PMID- 23160977
TI  - Low contrast- and low radiation dose protocol for cardiac CT of thin adults at
      256-row CT: usefulness of low tube voltage scans and the hybrid iterative
      reconstruction algorithm.
AB  - To evaluate the effect on image quality of a low contrast and radiation dose
      protocol for cardiac computed tomography (CT) using a low tube voltage, the
      hybrid-iterative reconstruction algorithm, and a 256-row CT scanner. Before
      clinical study, we performed phantom experiments to evaluate the hybrid iterative
      reconstruction technique. We randomly assigned 68 patients undergoing cardiac CT
      to one of two protocols; 33 were scanned with our conventional 120 kVp protocol,
      the contrast material (370 mgI/kg body weight) was delivered over 15 s. The other
      35 patients underwent scanning at a tube voltage of 80 kVp; the contrast dose,
      reduced by 50 % (185 mgI/kg), was delivered at the same fractional dose (24.7
      mgI/kg/s). The 80 kVp images were post-processed with the 60 % hybrid-iterative
      reconstruction technique. We evaluated the effective dose (ED), image noise, mean
      attenuation, and contrast-to-noise ratio (CNR) of each protocol. The hybrid
      iterative reconstruction technique offers almost same spatial resolution and
      noise-power-spectrum curve as compared with filtered back projection
      reconstruction. There were no decrease in spatial resolution and no shift of
      spatial frequency in noise power spectrum. The average ED was 74 % lower with the
      80- than the 120 kVp protocol (1.4 vs 5.4 mSv). Dunnett's test showed that there
      were no significant differences in the image noise, mean attenuation, and CNR
      between hybrid-iterative-reconstructed 80 kVp scans and 120 kVp scans (28.6 +/-
      6.5 vs 25.3 +/- 4.5, p = 0.18; 475.0 HU +/- 87.0 vs 445.3 HU +/- 67.7, p = 0.20;
      17.1 HU +/- 3.5 vs 17.8 HU +/- 3.1, p = 0.53). The low kVp scan and hybrid
      iterative reconstruction algorithm can dramatically decrease the radiation dose
      and contrast dose with adequate image quality at cardiac CT of thin adults using
      a 256-row CT scanner.

PMID- 23160980
TI  - Biosynthesis of nucleoside analogues via thermostable nucleoside phosphorylase.
AB  - Biocatalyzed synthesis of nucleoside analogues was carried out using two
      thermostable nucleoside phosphorylases from the hyperthermophilic aerobic
      crenarchaeon Aeropyrum pernix K1. The synthesis of the 2,6-diaminopurine
      nucleoside and 5-methyluridine was used as a reaction model to test the process.
      Both the purine nucleoside phosphorylase (apPNP) and uridine phosphorylase (apUP)
      were functionally expressed in Escherichia coli. The recombinant enzymes were
      characterized after purification, and both enzymes showed high thermostability
      and broad substrate specificity. Both enzymes retained 100 % of their activity
      after 60 min at high temperature, and the optimum temperature for the enzymes was
      90-100  degrees C. The nucleoside phosphorylases obtained from A. pernix are
      valuable industrial biocatalysts for high-temperature reactions that produce
      nucleoside drugs in high yields.

PMID- 23160979
TI  - Outpatient inguinal hernia repair under local anaesthesia: feasibility and
      efficacy of ultrasound-guided transversus abdominis plane block.
AB  - BACKGROUND: The aim of this prospective randomized study was to determine the
      utility of transversus abdominis plane (TAP) block to improve the efficacy of
      conventional local anaesthesia for hernia repair in order to achieve an adequate
      anaesthesia and to evaluate its post-operative analgesic effectiveness. METHOD:
      Hundred and fifty consecutive male patients undergoing outpatient hernia repair
      (Lichtenstein technique) were enrolled in this study. Patients were randomly
      allocated to undergo a combined TAP block and local anaesthesia (case group) or
      single conventional local anaesthesia (control group). The study was designed to
      obtain a 1:2 case-control ratio. The primary outcome was the evaluation of the
      proportion of patients achieving an adequate anaesthesia. The secondary outcome
      was the evaluation of pain on movement, pain at rest, rescue analgesia need,
      nausea and satisfaction. RESULTS: An adequate anaesthesia was achieved in 8 %
      case and in 36 % control subjects (p = 0.001). At the 6 and 12 h post-operative
      evaluations, patients enrolled in the case group reported significantly less pain
      (evaluated by VAS score) both at rest and on movement (p always = 0.001).
      Moreover, the need of rescue analgesia resulted significantly higher in the
      control group (14 vs. 32 %, p = 0.01). CONCLUSION: Our results demonstrated that,
      as compared with conventional local anaesthesia, the combination of TAP block
      with local anaesthesia showed a higher efficacy in the obtainment of an adequate
      anaesthesia and in the post-operative pain control for hernia repair.

PMID- 23160981
TI  - The novel Fh8 and H fusion partners for soluble protein expression in Escherichia
      coli: a comparison with the traditional gene fusion technology.
AB  - The Escherichia coli host system is an advantageous choice for simple and
      inexpensive recombinant protein production but it still presents bottlenecks at
      expressing soluble proteins from other organisms. Several efforts have been taken
      to overcome E. coli limitations, including the use of fusion partners that
      improve protein expression and solubility. New fusion technologies are emerging
      to complement the traditional solutions. This work evaluates two novel fusion
      partners, the Fh8 tag (8 kDa) and the H tag (1 kDa), as solubility enhancing tags
      in E. coli and their comparison to commonly used fusion partners. A broad range
      comparison was conducted in a small-scale screening and subsequently scaled-up.
      Six difficult-to-express target proteins (RVS167, SPO14, YPK1, YPK2, Frutalin and
      CP12) were fused to eight fusion tags (His, Trx, GST, MBP, NusA, SUMO, H and
      Fh8). The resulting protein expression and solubility levels were evaluated by
      sodium dodecyl sulfate polyacrylamide gel electrophoresis before and after
      protein purification and after tag removal. The Fh8 partner improved protein
      expression and solubility as the well-known Trx, NusA or MBP fusion partners. The
      H partner did not function as a solubility tag. Cleaved proteins from Fh8 fusions
      were soluble and obtained in similar or higher amounts than proteins from the
      cleavage of other partners as Trx, NusA or MBP. The Fh8 fusion tag therefore acts
      as an effective solubility enhancer, and its low molecular weight potentially
      gives it an advantage over larger solubility tags by offering a more reliable
      assessment of the target protein solubility when expressed as a fusion protein.

PMID- 23160982
TI  - Carotenoid and lipid production by the autotrophic microalga Chlorella
      protothecoides under nutritional, salinity, and luminosity stress conditions.
AB  - Today microalgae represent a viable alternative source for high-value products.
      The specie Chlorella protothecoides (Cp), heterotrophically grown, has been
      widely studied and provides a high amount of lutein and fatty acids (FA) and has
      a good profile for biodiesel production. This work studies carotenoid and FA
      production by autotrophic grown Cp. Cp was grown until the medium's nitrogen was
      depleted, then diluted in NaCl solution, resulting in nutritional, luminosity,
      and salinity stresses. Different NaCl concentrations were tested (10, 20, 30 g/L)
      at two different dilutions. After dilution, a color shifting from green to orange
      red was noticed, showing carotenoid production. The best production of both
      carotenoids and FA was attained with a 20 g/L NaCl solution. The total carotenoid
      content was 0.8 % w/w (canthaxanthin (23.3 %), echinenone (14.7 %), free
      astaxanthin (7.1 %), and lutein/zeaxanthin (4.1 %)). Furthermore, the total lipid
      content reached 43.4 % w/w, with a FA composition of C18:1 (33.64 %), C16:0
      (23.30 %), C18:2 (11.53 %), and less than 12 % of C18:3, which is needed to
      fulfill the biodiesel quality specifications (EN 14214).

PMID- 23160983
TI  - Glucocorticoid receptor-beta up-regulation and steroid resistance induction by IL
      17 and IL-23 cytokine stimulation in peripheral mononuclear cells.
AB  - PURPOSE: Most asthmatic patients have well controlled symptoms with regular
      treatment, but some require much higher doses of inhaled and oral
      corticosteroids, or in rare cases fail to respond; these patients may present Th
      17 cell infiltration and associated cytokines (IL-17A and -F) in the airways,
      sputum and peripheral blood. Because glucocorticoid receptor-beta (GR-beta) is
      associated with corticosteroid resistance, we investigated whether Th-17
      associated cytokines induce steroid insensitivity in PBMCs via GR-beta up
      regulation. METHODS: GR-alpha, GR-beta, GILZ and IL-6 expression were analyzed in
      PBMCs stimulated with IL-2/IL-4, IL-17A/IL-17F and IL-23 cytokines by
      quantitative RT-PCR. Dexamethasone-inhibition of PHA-induced proliferation and
      Dexamethasone-induced apoptosis were determined by either (3)H-thymidine or CFSE
      labelled cells and by Annexin-V staining and flow cytometry. RESULTS: IL-17 and
      IL-23 cytokines significantly increased GR-beta expression. IL-2/IL-4
      significantly decreased GR-alpha expression without affecting GR-beta. IL17, IL
      23 and IL2 + 4 stimulations significantly hampered Dexamethasone-inhibition of
      proliferation (Dex EC(50) for: IL-17A + F = 251 nM; IL-23 = 435 nM; IL2 + 4 = 950
      nM; Medium = 90 nM). IL2 + 4 and IL17A + F but not IL-23, significantly hampered
      Dexamethasone-induced apoptosis (1400 and 320 nM Dex, respectively).
      Dexamethasone's trans-activation of GILZ and trans-repression of NF-kB-driven IL
      6 expression were both inhibited by IL2 + 4; IL17 + IL23 antagonized Dex trans
      repression in PBMC from asthmatics. CONCLUSIONS: GR-beta up-regulation by IL
      17/IL-23 cytokines is associated with induced steroid insensitivity in PBMCs,
      observed as diminished Dexamethasone's effects on cell proliferation, apoptosis
      and gene regulation. Steroid resistance induced by IL-2/IL-4 was associated with
      decreased GR-alpha expression. This study supports the possibility that Th-17
      lymphocytes and associated cytokines play a role in the mechanism of steroid hypo
      responsiveness in severe asthmatics.

PMID- 23160984
TI  - Serum adenosine deaminase and total immunoglobulin G correlate with markers of
      immune activation and inversely with CD4 counts in asymptomatic, treatment-naive
      HIV infection.
AB  - PURPOSE: HIV-infection is characterized by aberrant immune activation and ongoing
      inflammation. Markers of inflammation are now recognized to have prognostic value
      for adverse events, independent of viral loads and CD4 counts. This study aimed
      to delineate a panel of affordable markers of immune activation in untreated HIV
      infection that may have an impact on the management of HIV in resource-limited
      settings. METHODS: This was a cross-sectional study of 86 untreated newly
      diagnosed HIV-infected patients and 54 matched controls attending a voluntary
      testing clinic in Cape Town, South Africa. Serum levels of adenosine deaminase
      (ADA), total immunoglobulin G (IgG), soluble CD14 and lipopolysaccharide-binding
      protein (LBP) were measured and correlated with CD4 counts, viral loads and
      expression of CD38 on CD8+ T cells. RESULTS: ADA, IgG and LBP were all
      significantly increased in the HIV infected group (p < 0.0001) compared with
      uninfected controls. Soluble CD14 was also significantly increased (p = 0.0187).
      Furthermore, all these parameters correlated inversely with CD4 counts (r = 
      0.481 p < 0.0001; r = -0.561; p < 0.0001; r = -0.387 p = 0.0007 and r = -0.254 p
      = 0.0240, respectively). Only ADA correlated with viral load (r = 0.260 p =
      0.0172). Importantly, ADA, IgG and LBP correlated directly with %CD38 on CD8+ T
      cells (r = 0.369 p < 0.0001; r = 0.284 p = 0.001; r = 0.408 p = 0.0006,
      respectively). CONCLUSION: Affordable parameters such as serum ADA and IgG
      correlated significantly with immune activation levels and markers of disease
      progression in untreated HIV-infection and therefore may add value to the
      management of these patients in resource-limited settings.

PMID- 23160986
TI  - Genomic and proteomic advances in autism research.
AB  - Recent studies suggest that adult neural stem cells (NSCs) may play a role in the
      pathogenesis of a number of the developmental disorders subsumed under the term
      autism spectrum disorders (ASD) that have in common impaired social interaction,
      communication deficits, and stereotypical behavior or interests. Since there is
      no "unifying hypothesis" about the etiology and pathogenesis of ASD, several
      factors have been associated with ASD, including genetic factors, physical co
      morbidity, disturbances of brain structure and function, biochemical anomalies,
      cognitive impairment, and disorders of speech and emotional development, mostly
      the lack of empathy. Most of disturbances of brain interconnectivity are regarded
      as main problem in autism. Since NSCs have a distinct life cycle in the mammalian
      brain consisting of proliferation, migration, arborization, integration into
      existing neuronal circuits, and myelinization, disturbances in NSCs
      differentiation is thought to be deleterious. In the current review, I will
      summarize the results of genomic and proteomic studies finding susceptibility
      genes and proteins for autism with regard to NSCs differentiation and maturation.

PMID- 23160985
TI  - High-capacity peptide-centric platform to decode the proteomic response to brain
      injury.
AB  - Traumatic brain injury (TBI) is a progressive disease process underlain by
      dynamic and interactive biochemical mechanisms; thus, large-scale and unbiased
      assessments are needed to fully understand its highly complex pathobiology. Here,
      we report on a new high-capacity label-free proteomic platform to evaluate the
      post-TBI neuroproteome. Six orthogonal separation stages and data-independent MS
      were employed, affording reproducible quantitative assessment on 18 651 peptides
      across biological replicates. From these data 3587 peptides were statistically
      responsive to TBI of which 18% were post-translationally modified. Results
      revealed as many as 484 proteins in the post-TBI neuroproteome, which was fully
      nine times the number determined from our prior study of focal cortical injury.
      Yet, these data were generated using 25 times less brain tissue per animal
      relative to former methodology, permitting greater anatomical specificity and
      proper biological replication for increased statistical power. Exemplified by
      these data, we discuss benefits of peptide-centric differential analysis to more
      accurately infer novel biological findings testable in future hypothesis-driven
      research. The high-capacity label-free proteomic platform is designed for multi
      factor studies aimed at expanding our knowledge on the molecular underpinnings of
      TBI and to develop better diagnostics and therapeutics.

PMID- 23160987
TI  - Mental health effects of Hurricane Sandy: characteristics, potential aftermath,
      and response.

PMID- 23160988
TI  - Interaction of D3 preferring agonist (-)-N6-(2-(4-(biphenyl-4-yl)piperazin-1
      yl)ethyl)-N6-propyl-4,5,6,7-tetrahydrobenzo[d]thiazole-2,6-diamine (D-264) with
      cloned human D2L, D2S, and D3 receptors: potent stimulation of mitogen-activated
      protein kinases and G protein-coupled inward rectifier potassium channels.
AB  - This study aims to determine the effect of the novel D(3) dopamine receptor
      agonist, D-264, on activation of D(3) and D(2) dopamine receptor signal
      transduction pathways and cell proliferation. AtT-20 neuroendocrine cells stably
      expressing human D(2S), D(2L), and D(3) dopamine receptors were treated with D
      264 and the coupling of the receptors to mitogen-activated protein kinase (MAPK)
      and G protein-coupled inward rectifier potassium (GIRK) channels was determined
      using Western blotting and whole-cell voltage clamp recording, respectively. D
      264 potently activated MAPK signaling pathway coupled to D(2S), D(2L), and D(3)
      dopamine receptors. The activation of MAPK was more pronounced than the reference
      agonist quinpirole and was longer lasting. D-264 also activated GIRK channels
      coupled to D(2S), D(2L), and D(3) receptors. In addition, D-264 dose-dependently
      induced cell proliferation in AtT-D(2L) and AtT-D(3) cells. These results
      indicate that D-264 robustly activates GIRK channels and MAPK coupled to D(2) and
      D(3) dopamine receptors in AtT-20 cells. D-264 is also a potent inducer of cell
      proliferation.

PMID- 23160989
TI  - Comparative signature diagrams to evaluate biophysical data for differences in
      protein structure across various formulations.
AB  - A solution to the problem of being able to show statistically significant
      differences in the measurements of various levels of higher-order protein
      structure has been an elusive one. We propose the use of comparative signature
      diagrams (CSDs) to this end. CSDs compare datasets from different biophysical
      techniques that fingerprint the secondary, tertiary, and quaternary structures of
      a protein molecule and display statistically significant differences in these
      datasets. In this paper, we explore the differences in the structures of two
      proteins (Granulocyte Colony Stimulating Factor [GCSF] and a monoclonal antibody
      [mAb]) in various formulations. These proteins were chosen based on the extent of
      differences in structure observed in the formulations. As an initial test, we
      utilize data from circular dichroism, 8-anilino-1-naphthalene-sulfonate and
      intrinsic fluorescence spectroscopy, and static light scattering measurements to
      fingerprint protein structure in the different formulations. Several layers of
      statistics were explored to visualize the regions of significant differences in
      the protein spectra. This approach provides a rapid, high-resolution methodology
      to compare various structural levels of proteins using standard biophysical
      instrumentation.

PMID- 23160990
TI  - Prevalence of human parechoviruses in central nervous system infections in
      children: a retrospective study in Shanghai, China.
AB  - Human parechoviruses (HPeV) are associated with central nervous system (CNS)
      infections and sepsis-like illnesses. However, data from China are not available.
      The aim of this study was to determine the prevalence, age, and seasonal
      distributions and genotypes of HPeV infections in children with CNS related
      disease in Shanghai, China. Of 776 cerebrospinal fluid (CSF) samples collected
      from children with CNS-related diseases under the age of 16 years during the
      years 2008-2011, 68 (9%) were identified to be HPeV positive. The annual
      prevalence varied remarkably: 1% (2/153) in 2008, 7% (12/177) in 2009, 15%
      (23/153) in 2010, and 11% (31/293) in 2011. The virus was detected in all age
      groups of children ranging from 2 days to 13 years and the median age was 14
      months. Of the 31 positive samples that were genotyped successfully, 28 were
      HPeV1 and 3 were HPeV3. This study provided data on the molecular epidemiology of
      HPeV infections in CNS-related diseases in Shanghai, China and suggest that the
      screening for HPeV by PCR should be included in the routine viral testing of CSF.

PMID- 23160991
TI  - The combined effect of surface chemistry and flow conditions on Staphylococcus
      epidermidis adhesion and ica operon expression.
AB  - The assessment of biomaterial susceptibility to infection relies mainly on the
      analysis of macroscopic bacterial responses to material interactions, usually
      under static conditions. However, new technologies permit a more profound
      understanding of the molecular basis of bacteria-biomaterial interactions. In
      this study, we combine both conventional phenotypic analysis - using confocal
      microscopy - and genotypic analysis - using the relative reverse transcription
      polymerase chain reaction (RT-PCR) - to examine the interaction of bacteria with
      OH- and CH3-terminated glass surfaces, under dynamic flow conditions. Bacterial
      adhesion, as well as slime production and biofilm formation, was much higher on
      the CH3-terminated than on the OH-terminated glass - for four Staphylococcus
      epidermidis strains. This was in agreement with the icaA and icaD gene expression
      results that showed increased expression for the bacteria adhering to the CH3
      terminated substrate, especially under the higher shear rate. Therefore, the
      combined effect of the surface chemistry and shear significantly influence the
      adhesion and phenotype of interacting bacterial cells, while there are putative
      links between phenotypic responses to bacteria-material interactions and gene
      expression profile alterations. This indicates that analysis of gene expression
      not only can greatly refine our knowledge of bacteria-material interactions, but
      also yield novel biomarkers for potential use in biocompatibility assessment.

PMID- 23160992
TI  - A novel model of in vitro osteocytogenesis induced by retinoic acid treatment.
AB  - Despite recent research which more and more stresses the importance of osteocytes
      in regulating bone and systemic mineral metabolism, current molecular and
      functional knowledge of osteocyte properties are still incomplete, mostly due to
      limited availability of in vitro models.  Osteocytes are terminally
      differentiated dendritic cells, and therefore are not easy to obtain and maintain
      in primary cultures. As an alternative, osteocyte differentiation can be induced
      by progressive osteoblast embedding in mineralised extracellular matrix. In this
      model, which is suitable for reproduction of bone development, the presence of
      calcified matrix prevents several cell biological methods from being used.
      Therefore, the osteocyte-like MLO-Y4 cell line continues to be the most widely
      used cellular system.  Here we show that treatment of primary osteoblasts or
      MC3T3-E1 cells with retinoic acid generates a homogeneous population of ramified
      cells with osteocyte features, as confirmed by morphological and molecular
      analyses. The first morphological changes are detectable in primary cells after 2
      days of treatment, and in the cell line after 4 days of treatment.
      Differentiation is complete in 5 and 10 days, respectively, with progressive
      development of dendrites, loss of the ability to produce extracellular matrix,
      down-regulation of osteoblast markers, and up-regulation of osteocyte-specific
      molecules, most notably among them sclerostin.  Compared to other published
      protocols, our method has a number of advantages. It is easy to perform and does
      not require special instrumentation, it is highly reproducible, and rapidly
      generates a mature osteocyte population in the complete absence of extracellular
      matrix, allowing the use of these cells for unlimited biological applications.

PMID- 23160993
TI  - Predatory caddisfly larvae sequester tetrodotoxin from their prey, eggs of the
      rough-skinned newt (Taricha granulosa).
AB  - Caddisfly larvae (Limnophilus spp.) are important predators of eggs of the rough
      skinned newt (Taricha granulosa). Newts may possess extremely large quantities of
      the neurotoxin tetrodotoxin (TTX) in their skin, and females may provision this
      toxin in their eggs. Using a competitive inhibition enzymatic immunoassay, we
      examined TTX-resistant caddisflies, sympatric with the known most toxic
      population of newts, for the presence of TTX. We found that caddisflies sequester
      TTX after consuming eggs in the laboratory. Caddisfly larvae that were frozen
      immediately after collecting in the wild possessed TTX. Finally, wild-caught
      larvae reared on a TTX-free diet in the laboratory retained TTX for up to 134
      days, through metamorphosis and into the adult stage.

PMID- 23160995
TI  - CLN5 and CLN8 protein association with ceramide synthase: biochemical and
      proteomic approaches.
AB  - Four patients with juvenile neuronal ceroid lipofuscinoses, a childhood
      neurodegenerative disorder that was previously described as CLN9 variant, are
      reclassified as CLN5 disease. CLN5-deficient (CLN5(-/-) ) fibroblasts demonstrate
      adhesion defects, increased growth, apoptosis, and decreased levels of ceramide,
      sphingomyelin, and glycosphingolipids. The CLN8 protein (CLN8p) corrects growth
      and apoptosis in CLN5(-/-) cells. Related proteins containing a Lag1 motif
      (CerS1/2/4/5/6) partially corrected these deficits, with CerS1, which is
      primarily expressed in brain, providing the best complementation, suggesting
      CLN5p activates CerS1 and may co-immunoprecipitate with it. CLN8p complements
      CLN5-deficient cells, consolidating the interrelationship of CLN5p/CLN8p, whose
      potential roles are explored as activators of (dihydro)ceramide synthases.
      Homozygosity mapping using microarray technology led to identification of CLN5 as
      the culprit gene in previously classified CLN9-defective cases. Similar to CLN5(
      /-) cells, ceramide synthase activity, C16/C18:0/C24:0/C24:1 ceramide species,
      measured by MS is decreased in CLN8(-/-) cells. Comparison of normal versus CLN5(
      /-) cell CerS1-bound proteins by immunoprecipitation, differential gel
      electrophoresis, and MS revealed absence of gamma-actin in CLN5(-/-) cells. The
      gamma-actin gene sequence is normal in CLN5(-/-) derived DNA. The gamma-actin
      bound proteins, vimentin and histones H2Afz/H3F3A/Hist1H4, were absent from the
      gamma-actin protein complex in CLN5(-/-) cells. The function of CLN5p may require
      vimentin and the histone proteins to bind gamma-actin. Defective binding could
      explain the CLN5(-/-) cellular phenotype. We explore the role of the CLN5/CLN8
      proteins in ceramide species specific sphingolipid de novo synthesis, and suggest
      that CLN5/CLN8 proteins are more closely related than previously believed.

PMID- 23160996
TI  - Trajectories of perceived emotional and physical distress in patients with an
      implantable cardioverter defibrillator.
AB  - BACKGROUND: Little is known about the course of emotional and physical distress
      in patients with an implantable cardioverter defibrillator (ICD). PURPOSE: We
      examined (1) trajectories of emotional and physical distress in the first 18
      months postimplantation and (2) predictors of these trajectories, including
      demographical, clinical, and personality factors. METHODS: Dutch patients with an
      ICD (N = 645) completed measures on anxiety, depression, somatic symptoms, and
      perceived disability at the time of implantation, and 2, 12, and 18 months
      postimplantation. Measures on Type D personality (tendency to inhibit the
      expression of negative emotions) and anxiety sensitivity (tendency to fear
      anxiety-related sensations) were also completed at baseline. RESULTS: Latent
      class analysis (LatentGOLD) identified six to seven distinct trajectories,
      varying largely in overall levels of distress, and remaining relatively stable
      after a small initial decline. Multinomial regression showed that Type D
      personality and anxiety sensitivity were the most prominent predictors,
      particularly of trajectories that reflected higher distress levels. Cardiac
      resynchronization therapy and coronary artery disease also increased the risk for
      distress, whereas ICD indication and shocks did not. CONCLUSIONS: The course of
      emotional and physical distress may be relatively stable after ICD implantation.
      In clinical practice, identification of patients with high risk of higher levels
      of emotional and physical distress may be warranted; as such, patients with high
      levels of anxiety sensitivity or a Type D personality should be identified and
      offered behavioral support.

PMID- 23160997
TI  - Cardiovascular reactivity and cardiometabolic risk in adolescents.
AB  - BACKGROUND: Cardiovascular reactivity has been examined as a risk marker or
      factor in the pathogenesis of hypertension or cardiovascular disease, but few
      have examined the relationship with the metabolic syndrome. PURPOSE: We examined
      whether cardiovascular reactivity to laboratory stress is associated with
      individual cardiometabolic risk factors and their co-occurrence. A significant
      positive relationship was hypothesized for both individual and clustered risk
      factors in their cross-sectional associations with reactivity to multiple
      stressors. METHODS: A sample of 144, 15-17-year-old adolescents (74 % boys)
      largely from ethnic minority groups (54 % Hispanic White, 26 % Black) were
      identified at annual blood pressure (BP) screening (39 % with elevated BP) at
      high schools in Miami, Florida, USA. Participants completed the evaluated
      speaking, mirror star tracing, and cold pressor tasks, as well as cardiometabolic
      risk factor blood sampling. Participants were classified into metabolic syndrome
      criterion groups (0, 1, 2, or >=3 criteria) based on American Heart Association
      adult criteria. RESULTS: Multiple regression analyses with individual metabolic
      syndrome variables demonstrated that diastolic (D)BP reactivity during the mirror
      star tracing task accounted for 1.3 %, 3.8 %, and 5.1 % of the respective
      variances in casual systolic BP, waist circumference, and triglycerides (ps <
      0.05). In multinomial logistic regression models, increased DBP reactivity during
      mirror star tracing and cold pressor tasks, and decreased HR reactivity during
      the cold pressor, were associated with greater likelihood of risk factor co
      occurrence (ranging from 8.3 % to 15.8 %). CONCLUSIONS: Findings indicate that
      autonomic reactivity to the mirror star tracing and cold pressor tasks, but not
      the evaluated speaking task, is associated with risk factor co-occurrence, and
      reactivity may be a clinical prognosticator of cardiometabolic disease risk.

PMID- 23160998
TI  - Human biodistribution and dosimetry of 18F-JNJ42259152, a radioligand for
      phosphodiesterase 10A imaging.
AB  - PURPOSE: Phosphodiesterase 10A (PDE10A) is a cAMP/cGMP-hydrolysing enzyme with a
      central role in striatal signalling and implicated in neuropsychiatric disorders
      such as Huntington's disease, Parkinson's disease, schizophrenia and addiction.
      We have developed a novel PDE10A PET ligand, (18)F-JNJ42259152, and describe here
      its human dynamic biodistribution, safety and dosimetry. METHODS: Six male
      subjects (age range 23-67 years) underwent ten dynamic whole-body PET/CT scans
      over 6 h after bolus injection of 175.5 +/- 9.4 MBq (18)F-JNJ42259152. Source
      organs were delineated on PET/CT and individual organ doses and effective dose
      were determined using the OLINDA software. RESULTS: F-JNJ42259152 was readily
      taken up by the brain and showed exclusive retention in the brain, especially in
      the striatum with good washout starting after 20 min. The tracer was cleared
      through both the hepatobiliary and the urinary routes. No defluorination was
      observed. Organ absorbed doses were largest for the gallbladder (239 MUSv/MBq)
      and upper large intestine (138 MUSv/MBq). The mean effective dose was 24.9 +/-
      4.1 MUSv/MBq. No adverse events were encountered. CONCLUSION: In humans, (18)F
      JNJ42259152 has an appropriate distribution, brain kinetics and safety. The
      estimated effective dose was within WHO class IIb with low interindividual
      variability. Therefore, the tracer is suitable for further kinetic evaluation in
      humans.

PMID- 23160999
TI  - European multicentre database of healthy controls for [123I]FP-CIT SPECT (ENC
      DAT): age-related effects, gender differences and evaluation of different methods
      of analysis.
AB  - PURPOSE: Dopamine transporter (DAT) imaging with [(123)I]FP-CIT (DaTSCAN) is an
      established diagnostic tool in parkinsonism and dementia. Although qualitative
      assessment criteria are available, DAT quantification is important for research
      and for completion of a diagnostic evaluation. One critical aspect of
      quantification is the availability of normative data, considering possible age
      and gender effects on DAT availability. The aim of the European Normal Control
      Database of DaTSCAN (ENC-DAT) study was to generate a large database of
      [(123)I]FP-CIT SPECT scans in healthy controls. METHODS: SPECT data from 139
      healthy controls (74 men, 65 women; age range 20-83 years, mean 53 years)
      acquired in 13 different centres were included. Images were reconstructed using
      the ordered-subset expectation-maximization algorithm without correction
      (NOACSC), with attenuation correction (AC), and with both attenuation and scatter
      correction using the triple-energy window method (ACSC). Region-of-interest
      analysis was performed using the BRASS software (caudate and putamen), and the
      Southampton method (striatum). The outcome measure was the specific binding ratio
      (SBR). RESULTS: A significant effect of age on SBR was found for all data. Gender
      had a significant effect on SBR in the caudate and putamen for the NOACSC and AC
      data, and only in the left caudate for the ACSC data (BRASS method). Significant
      effects of age and gender on striatal SBR were observed for all data analysed
      with the Southampton method. Overall, there was a significant age-related decline
      in SBR of between 4 % and 6.7 % per decade. CONCLUSION: This study provides a
      large database of [(123)I]FP-CIT SPECT scans in healthy controls across a wide
      age range and with balanced gender representation. Higher DAT availability was
      found in women than in men. An average age-related decline in DAT availability of
      5.5 % per decade was found for both genders, in agreement with previous reports.
      The data collected in this study may serve as a reference database for nuclear
      medicine centres and for clinical trials using [(123)I]FP-CIT SPECT as the
      imaging marker.

PMID- 23161000
TI  - Reply to comment on Pepe et al.: Somatostatin receptor SPECT.

PMID- 23161002
TI  - Quantitative proteomic analysis reveals that lipopolysaccharide induces mitogen
      activated protein kinase-dependent activation in human microglial cells.
AB  - Microglial cells act as the first and main form of active immune defense in the
      central nervous system related to inflammation and neurodegenerative disease.
      Lipopolysaccharide (LPS) induces many genes encoding inflammatory mediators,
      including cytokines such as tumor necrosis factor-alpha, interleukin-1beta, (IL
      1beta), and IL-6, chemokines, and prostaglandins in microglial cells.
      Quantitative proteomics methods with isobaric chemical labeling using tandem mass
      tags and 2D-nano LC-ESI-MS/MS were used to systematically analyze proteomic
      changes in microglia responding to LPS stimulation. As a result, we found that
      the expression level of 21 proteins in human microglial cells changed after
      activation. Among those, one of the strong mitogen-activated protein kinase
      (MAPK) regulator proteins, CMPK1 was highly upregulated after LPS stimulation in
      human microglial cells. We detected and validated upregulation of MAPK including
      ERK1/2, p38, and SAPK/JNK by immunohistochemistry and Western blotting. NFkappaB,
      strong transcription factor of CMPK1, was translocated to the nucleus from the
      cytosol by high contents screening after LPS stimulation. Taken together, we
      conclude that MAPK signaling plays an important role in LPS-induced human
      microglial activation related to inflammatory response.

PMID- 23161001
TI  - Yohimbine increases opioid-seeking behavior in heroin-dependent, buprenorphine
      maintained individuals.
AB  - RATIONALE: In laboratory animals, the biological stressor yohimbine (alpha(2)
      noradrenergic autoreceptor antagonist) promotes drug seeking. Human laboratory
      studies have demonstrated that psychological stressors can increase drug craving
      but not that stressors alter drug seeking. OBJECTIVES: This clinical study tested
      whether yohimbine increases opioid-seeking behavior. METHODS: Ten heroin
      dependent, buprenorphine-stabilized (8 mg/day) volunteers sampled two doses of
      hydromorphone [12 and 24 mg IM in counterbalanced order, labeled drug A (session
      1) and drug B (session 2)]. During each of six later sessions (within-subject,
      double-blind, randomized crossover design), volunteers could respond on a 12
      trial choice progressive ratio task to earn units (1 or 2 mg) of the sampled
      hydromorphone dose (drug A or B) vs money ($2) following different oral yohimbine
      pretreatment doses (0, 16.2, and 32.4 mg). RESULTS: Behavioral economic demand
      intensity and peak responding (O (max)) were significantly higher for
      hydromorphone 2 than 1 mg. Relative to placebo, yohimbine significantly increased
      hydromorphone demand inelasticity, more so for hydromorphone 1-mg units (P (max)
      = 909, 3,647, and 3,225 for placebo, 16.2, and 32.4 mg yohimbine doses,
      respectively) than hydromorphone 2-mg units (P (max) = 2,656, 3,193, and 3,615,
      respectively). Yohimbine produced significant but clinically modest dose
      dependent increases in blood pressure (systolic ~ 15 and diastolic ~ 10 mmHg) and
      opioid withdrawal symptoms, and decreased opioid agonist symptoms and elated
      mood. CONCLUSIONS: These findings concur with preclinical data by demonstrating
      that yohimbine increases drug seeking; in this study, these effects occurred
      without clinically significant subjective distress or elevated craving, and
      partly depended on opioid unit dose.

PMID- 23161003
TI  - Attentional capture by the onset and offset of motion signals outside the spatial
      focus of attention.
AB  - The present study examined whether participants were able to ignore a task
      irrelevant commencement or cessation of optic flow while they were engaging in a
      letter-identification task, as claimed by adherents of the view that attentional
      set determines deployment of attention, or whether irrelevant events would
      capture attention regardless of observers' attentional set, as claimed by
      adherents of a broad range of views emphasizing the behavioral urgency of
      stimulus motion. Observers identified a green letter in a central rapid stream of
      heterogeneously colored nontargets. A completely task-irrelevant optic flow
      occurred in the periphery. If attentional deployment were governed by a top-down
      attentional set, the letter identification would be unaffected by the temporal
      change in the optic flow. The results reflected attentional capture by
      commencement or cessation of optic flow, which is inconsistent with the top-down
      view. When the peripheral dots expanded at various speeds before onset of the
      target, identification was impaired relative to when no motion occurred. Mere
      commencement or cessation of motion was sufficient to produce the capture effect.
      Qualitative (commencement or cessation) rather than quantitative changes
      (acceleration or deceleration) of the motion display were critical for the
      occurrence of attentional capture. We conclude that salient discontinuities in
      optic flow induce attentional capture when observers search for a feature in a
      different stimulus domain, an idea implying a unique role for of expanding global
      motion in the deployment of visual attention.

PMID- 23161004
TI  - Overview: what are helicases?
AB  - First discovered in the 1970s, DNA helicases were initially described as enzymes
      that use chemical energy to separate (i.e., to unwind) the complementary strands
      of DNA. Because helicases are ubiquitous, display a range of fascinating
      biochemical activities, and are involved in all aspects of DNA metabolism,
      defects in human helicases are linked to a variety of genetic disorders, and
      helicase research continues to be important in understanding the molecular basis
      of DNA replication, recombination, and repair. The purpose of this book is to
      organize this information and to update the traditional view of these enzymes,
      because it is now evident that not all helicases possess bona fide strand
      separation activity and may function instead as energy-dependent switches or
      translocases. In this chapter, we will first discuss the biochemical and
      structural features of DNA-the lattice on which helicases operate-and its
      cellular organization. We will then provide a historical overview of helicases,
      starting from their discovery and classification, leading to their structures,
      mechanisms, and biomedical significance. Finally, we will highlight several key
      advances and developments in helicase research, and summarize some remaining
      questions and active areas of investigation. The subsequent chapters will discuss
      these topics and others in greater detail and are written by experts of these
      respective fields.

PMID- 23161006
TI  - Structure and Mechanisms of SF2 DNA Helicases.
AB  - Effective transcription, replication, and maintenance of the genome require a
      diverse set of molecular machines to perform the many chemical transactions that
      constitute these processes. Many of these machines use single-stranded nucleic
      acids as templates, and their actions are often regulated by the participation of
      nucleic acids in multimeric structures and macromolecular assemblies that
      restrict access to chemical information. Superfamily II (SF2) DNA helicases and
      translocases are a group of molecular machines that remodel nucleic acid lattices
      and enable essential cellular processes to use the information stored in the
      duplex DNA of the packaged genome. Characteristic accessory domains associated
      with the subgroups of the superfamily direct the activity of the common motor
      core and expand the repertoire of activities and substrates available to SF2 DNA
      helicases, translocases, and large multiprotein complexes containing SF2 motors.
      In recent years, single-molecule studies have contributed extensively to the
      characterization of this ubiquitous and essential class of enzymes.

PMID- 23161007
TI  - Structure and mechanism of hexameric helicases.
AB  - Hexameric helicases are responsible for many biological processes, ranging from
      DNA replication in various life domains to DNA repair, transcriptional regulation
      and RNA metabolism, and encompass superfamilies 3-6 (SF3-6).To harness the
      chemical energy from ATP hydrolysis for mechanical work, hexameric helicases have
      a conserved core engine, called ASCE, that belongs to a subdivision of the P-loop
      NTPases. Some of the ring helicases (SF4 and SF5) use a variant of ASCE known as
      RecA-like, while some (SF3 and SF6) use another variant known as AAA+ fold. The
      NTP-binding sites are located at the interface between monomers and include amino
      acid residues coming from neighbouring subunits, providing a mean for small
      structural changes within the ATP-binding site to be amplified into large inter
      subunit movement.The ring structure has a central channel which encircles the
      nucleic acid. The topological link between the protein and the nucleic acid
      substrate increases the stability and processivity of the enzyme. This is
      probably the reason why within cellular systems the critical step of unwinding
      dsDNA ahead of the replication fork seems to be almost invariably carried out by
      a toroidal helicase, whether in bacteria, archaea or eukaryotes, as well as in
      some viruses.Over the last few years, a large number of biochemical, biophysical
      and structural data have thrown new light onto the architecture and function of
      these remarkable machines. Although the evidence is still limited to a couple of
      systems, biochemical and structural results suggest that motors based on RecA and
      AAA+ folds have converged on similar mechanisms to couple ATP-driven
      conformational changes to movement along nucleic acids.

PMID- 23161008
TI  - Helicases at the replication fork.
AB  - Helicases are fundamental components of all replication complexes since unwinding
      of the double-stranded template to generate single-stranded DNA is essential to
      direct DNA synthesis by polymerases. However, helicases are also required in many
      other steps of DNA replication. Replicative helicases not only unwind the
      template DNA but also play key roles in regulating priming of DNA synthesis and
      coordination of leading and lagging strand DNA polymerases. Accessory helicases
      also aid replicative helicases in unwinding of the template strands in the
      presence of proteins bound to the DNA, minimising the risks posed by
      nucleoprotein complexes to continued fork movement. Helicases also play critical
      roles in Okazaki fragment processing in eukaryotes and may also be needed to
      minimise topological problems when replication forks converge. Thus fork
      movement, coordination of DNA synthesis, lagging strand maturation and
      termination of replication all depend on helicases. Moreover, if disaster strikes
      and a replication fork breaks down then reloading of the replication machinery is
      effected by helicases, at least in bacteria. This chapter describes how helicases
      function in these multiple steps at the fork and how DNA unwinding is coordinated
      with other catalytic processes to ensure efficient, high fidelity duplication of
      the genetic material in all organisms.

PMID- 23161005
TI  - Structure and Mechanisms of SF1 DNA Helicases.
AB  - Superfamily I is a large and diverse group of monomeric and dimeric helicases
      defined by a set of conserved sequence motifs. Members of this class are involved
      in essential processes in both DNA and RNA metabolism in all organisms. In
      addition to conserved amino acid sequences, they also share a common structure
      containing two RecA-like motifs involved in ATP binding and hydrolysis and
      nucleic acid binding and unwinding. Unwinding is facilitated by a "pin" structure
      which serves to split the incoming duplex. This activity has been measured using
      both ensemble and single-molecule conditions. SF1 helicase activity is modulated
      through interactions with other proteins.

PMID- 23161010
TI  - The helicase-primase complex as a target for effective herpesvirus antivirals.
AB  - Herpes simplex virus and varicella-zoster virus have been treated for more that
      half a century using nucleoside analogues. However, there is still an unmet
      clinical need for improved herpes antivirals. The successful compounds,
      acyclovir; penciclovir and their orally bioavailable prodrugs valaciclovir and
      famciclovir, ultimately block virus replication by inhibiting virus-specific DNA
      polymerase. The helicase-primase (HP) complex offers a distinctly different
      target for specific inhibition of virus DNA synthesis. This review describes the
      synthetic programmes that have already led to two HP-inhibitors (HPI) that have
      commenced clinical trials in man. One of these (known as AIC 316) continues in
      clinical development to date. The specificity of HPI is reflected by the ability
      to select drug-resistant mutants. The role of HP-antiviral resistance will be
      considered and how the study of cross--resistance among mutants already shows
      subtle differences between compounds in this respect. The impact of resistance on
      the drug development in the clinic will also be considered. Finally, herpesvirus
      latency remains as the most important barrier to a therapeutic cure. Whether or
      not helicase primase inhibitors alone or in combination with nucleoside analogues
      can impact on this elusive goal remains to be seen.

PMID- 23161009
TI  - DNA helicases associated with genetic instability, cancer, and aging.
AB  - DNA helicases have essential roles in the maintenance of genomic -stability. They
      have achieved even greater prominence with the discovery that mutations in human
      helicase genes are responsible for a variety of genetic disorders and are
      associated with tumorigenesis. A number of missense mutations in human helicase
      genes are linked to chromosomal instability diseases characterized by age-related
      disease or associated with cancer, providing incentive for the characterization
      of molecular defects underlying aberrant cellular phenotypes. In this chapter, we
      discuss some examples of clinically relevant missense mutations in various human
      DNA helicases, particularly those of the Iron-Sulfur cluster and RecQ families.
      Clinically relevant mutations in the XPD helicase can lead to Xeroderma
      pigmentosum, Cockayne's syndrome, Trichothiodystrophy, or COFS syndrome. FANCJ
      mutations are associated with Fanconi anemia or breast cancer. Mutations of the
      Fe-S helicase ChlR1 (DDX11) are linked to Warsaw Breakage syndrome. Mutations in
      the RecQ helicases BLM and WRN are linked to the cancer-prone disorder Bloom's
      syndrome and premature aging condition Werner syndrome, respectively. RECQL4
      mutations can lead to Rothmund-Thomson syndrome, Baller-Gerold syndrome, or
      RAPADILINO. Mutations in the Twinkle mitochondrial helicase are responsible for
      several neuromuscular degenerative disorders. We will discuss some insights
      gained from biochemical and genetic studies of helicase variants, and highlight
      some hot areas of helicase research based on recent developments.

PMID- 23161011
TI  - RecQ Helicases: Conserved Guardians of Genomic Integrity.
AB  - The RecQ family of DNA helicases is highly conserved throughout -evolution, and
      is important for the maintenance of genome stability. In humans, five RecQ family
      members have been identified: BLM, WRN, RECQ4, RECQ1 and RECQ5. Defects in three
      of these give rise to Bloom's syndrome (BLM), Werner's syndrome (WRN) and
      Rothmund-Thomson/RAPADILINO/Baller-Gerold (RECQ4) syndromes. These syndromes are
      characterised by cancer predisposition and/or premature ageing. In this review,
      we focus on the roles of BLM and its S. cerevisiae homologue, Sgs1, in genome
      maintenance. BLM/Sgs1 has been shown to play a critical role in homologous
      recombination at multiple steps, including end-resection, displacement loop
      formation, branch migration and double Holliday junction dissolution. In
      addition, recent evidence has revealed a role for BLM/Sgs1 in the stabilisation
      and repair of replication forks damaged during a perturbed S-phase. Finally BLM
      also plays a role in the suppression and/or resolution of ultra-fine anaphase DNA
      bridges that form between sister-chromatids during mitosis.

PMID- 23161013
TI  - DNA Helicases in NER, BER, and MMR.
AB  - Different DNA repair mechanisms have evolved to protect our genome from
      modifications caused by endogenous and exogenous agents, thus maintaining the
      integrity of the DNA. Helicases often play a central role in these repair
      pathways and have shown to be essential for diverse tasks within these
      mechanisms. In prokaryotic nucleotide excision repair (NER) for example the two
      helicases UvrB and UvrD assume vastly different functions. While UvrB is
      intimately involved in damage verification and acts as an anchor for the other
      prokaryotic NER proteins UvrA and UvrC, UvrD is required to resolve the post
      incision complex leading to the release of UvrC and the incised ssDNA fragment.
      For the XPD helicase in eukaryotic NER a similar function in analogy to UvrB has
      been proposed, whereas XPB the second helicase uses only its ATPase activity
      during eukaryotic NER. In prokaryotic mismatch repair (MMR) UvrD again plays a
      central role. The different tasks of this protein in the different repair
      pathways highlight the importance of regulative protein-protein interactions to
      fine-tune its helicase activity. In other DNA repair pathways the role of the
      helicases involved is sometimes not as well characterized, and no helicase has so
      far been described to assume the function of UvrD in eukaryotic MMR. RecQ
      helicases and FancJ interact with eukaryotic MMR proteins but their involvement
      in this repair pathway is unclear. Lastly, long-patch base excision repair is
      linked to the WRN helicase and many proteins within this pathway interact with
      the helicase leading to increased activity of the interacting proteins as
      observed for pol beta and FEN-1 or the helicase itself is negatively regulated
      through the interaction with APE-1. However, compared to the precise functions
      described for the helicases in the other DNA repair mechanisms the role of WRN in
      BER remains speculative and requires further analysis.

PMID- 23161014
TI  - Roles for Helicases as ATP-Dependent Molecular Switches.
AB  - On the basis of the familial name, a "helicase" might be expected to have an
      enzymatic activity that unwinds duplex polynucleotides to form single strands. A
      more encompassing taxonomy that captures alternative enzymatic roles has defined
      helicases as a sub-class of molecular motors that move directionally and
      processively along nucleic acids, the so-called "translocases". However, even
      this definition may be limiting in capturing the full scope of helicase mechanism
      and activity. Discussed here is another, alternative view of helicases-as
      machines which couple NTP-binding and hydrolysis to changes in protein
      conformation to resolve stable nucleoprotein assembly states. This "molecular
      switch" role differs from the classical view of helicases as molecular motors in
      that only a single catalytic NTPase cycle may be involved. This is illustrated
      using results obtained with the DEAD-box family of RNA helicases and with a model
      bacterial system, the ATP-dependent Type III restriction-modification enzymes.
      Further examples are discussed and illustrate the wide-ranging examples of
      molecular switches in genome metabolism.

PMID- 23161012
TI  - Roles of DNA helicases in the mediation and regulation of homologous
      recombination.
AB  - Homologous recombination (HR) is an evolutionarily conserved process that
      eliminates DNA double-strand breaks from chromosomes, repairs injured DNA
      replication forks, and helps orchestrate meiotic chromosome segregation. Recent
      studies have shown that DNA helicases play multifaceted roles in HR mediation and
      regulation. In particular, the S. cerevisiae Sgs1 helicase and its human ortholog
      BLM helicase are involved in not only the resection of the primary lesion to
      generate single-stranded DNA to prompt the assembly of the HR machinery, but they
      also function in somatic cells to suppress the formation of chromosome arm
      crossovers during HR. On the other hand, the S. cerevisiae Mph1 and Srs2
      helicases, and their respective functional equivalents in other eukaryotes,
      suppress spurious HR events and favor the formation of noncrossovers via distinct
      mechanisms. Thus, the functional integrity of the HR process and HR outcomes are
      dependent upon these helicase enzymes. Since mutations in some of these helicases
      lead to cancer predisposition in humans and mice, studies on them have clear
      relevance to human health and disease.

PMID- 23161015
TI  - The FtsK Family of DNA Pumps.
AB  - Interest for proteins of the FtsK family initially arose from their implication
      in many primordial processes in which DNA needs to be transported from one cell
      compartment to another in eubacteria. In the first section of this chapter, we
      address a list of the cellular functions of the different members of the FtsK
      family that have been so far studied. Soon after their discovery, interest for
      the FstK proteins spread because of their unique biochemical properties: most DNA
      transport systems rely on the assembly of complex multicomponent machines. In
      contrast, six FtsK proteins are sufficient to assemble into a fast and powerful
      DNA pump; the pump transports closed circular double stranded DNA molecules
      without any covalent-bond breakage nor topological alteration; transport is
      oriented despite the intrinsic symmetrical nature of the double stranded DNA
      helix and can occur across cell membranes. The different activities required for
      the oriented transport of DNA across cell compartments are achieved by three
      separate modules within the FtsK proteins: a DNA translocation module, an
      orientation module and an anchoring module. In the second part of this chapter,
      we review the structural and biochemical properties of these different modules.

PMID- 23161016
TI  - ATP-Dependent Chromatin Remodeling.
AB  - In the eukaryotic nucleus, processes of DNA metabolism such as transcription, DNA
      replication, and repair occur in the context of DNA packaged into nucleosomes and
      higher order chromatin structures. In order to overcome the barrier presented by
      chromatin structures to the protein machinery carrying out these processes, the
      cell relies on a class of enzymes called chromatin remodeling complexes which
      catalyze ATP-dependent restructuring and repositioning of nucleosomes. Chromatin
      remodelers are large multi-subunit complexes which all share a common SF2
      helicase ATPase domain in their catalytic subunit, and are classified into four
      different families-SWI/SNF, ISWI, CHD, INO80-based on the arrangement of other
      domains in their catalytic subunit as well as their non-catalytic subunit
      composition. A large body of structural, biochemical, and biophysical evidence
      suggests chromatin remodelers operate as histone octamer-anchored directional DNA
      translocases in order to disrupt DNA-histone interactions and catalyze nucleosome
      sliding. Remodeling mechanisms are family-specific and depend on factors such as
      how the enzyme engages with nucleosomal and linker DNA, features of DNA loop
      intermediates, specificity for mono- or oligonucleosomal substrates, and ability
      to remove histones and exchange histone variants. Ultimately, the biological
      function of chromatin remodelers and their genomic targeting in vivo is regulated
      by each complex's subunit composition, association with chromatin modifiers and
      histone chaperones, and affinity for chromatin signals such as histone
      posttranslational modifications.

PMID- 23161017
TI  - Assessment of plant lectin antifungal potential against yeasts of major
      importance in medical mycology.
AB  - The search for new compounds with antifungal activity is accelerating due to
      rising yeast and fungal resistance to commonly prescribed drugs. Among the
      molecules being investigated, plant lectins can be highlighted. The present work
      shows the potential of six plant lectins which were tested in vitro against
      yeasts of medical importance, Candida albicans, Candida tropicalis, Candida
      parapsilosis, Cryptococcus gattii, Cryptococcus neoformans, Malassezia
      pachydermatis, Rhodotorula sp. and Trichosporon sp. Broth microdilution
      susceptibility testing was performed in accordance with standard protocols to
      evaluate antifungal activity. Minimum inhibitory concentration (MIC) was
      determined at 80% yeast growth inhibition, whereas the minimum fungicidal
      concentration (MFC) was evaluated after making the subcultures of each dilution.
      Only C. parapsilosis growth was inhibited by the lectins tested. Abelmoschus
      esculentus lectin showed the highest MIC (0.97 MUg ml(-1)). Lectins from
      Canavalia brasiliensis, Mucuna pruriens and Clitoria fairchildiana presented the
      highest MFC at (3.90 MUg ml(-1)). These results encourage further studies with
      wider yeast strain selections, and open new perspectives for the development of
      pharmacological molecules.

PMID- 23161018
TI  - The lichen connections of black fungi.
AB  - Many black meristematic fungi persist on rock surfaces-hostile and exposed
      habitats where high doses of radiation and periods of desiccation alternate with
      rain and temperature extremes. To cope with these extremes, rock-inhabiting black
      fungi show phenotypic plasticity and produce melanin as cell wall pigments. The
      rather slow growth rate seems to be an additional prerequisite to oligotrophic
      conditions. At least some of these fungi can undergo facultative, lichen-like
      associations with photoautotrophs. Certain genera presenting different lifestyles
      are phylogenetic related among the superclass Dothideomyceta. In this paper, we
      focus on the genus Lichenothelia, which includes border-line lichens, that is,
      associations of melanised fungi with algae without forming proper lichen thalli.
      We provide a first phylogenetic hypothesis to show that Lichenothelia belongs to
      the superclass Dothideomyceta. Further, culture experiments revealed the presence
      of co-occurring fungi in Lichenothelia thalli. These fungi are related to plant
      pathogenic fungi (Mycosphaerellaceae) and to other rock-inhabiting lineages
      (Teratosphaeriaceae). The Lichenothelia thallus-forming fungi represent therefore
      consortia of different black fungal strains. Our results suggest a common link
      between rock-inhabiting meristematic and lichen-forming lifestyles of
      ascomycetous fungi.

PMID- 23161020
TI  - Designs and challenges for personalized medicine studies in oncology: focus on
      the SHIVA trial.
AB  - Personalized medicine is defined by the National Cancer Institute as "a form of
      medicine that uses information about a person's genes, proteins, and environment
      to prevent, diagnose, and treat disease." In oncology, the term "personalized
      medicine" arose with the emergence of molecularly targeted agents. The
      prescription of approved molecularly targeted agents to cancer patients currently
      relies on the primary tumor location and histological subtype. Predictive
      biomarkers of efficacy of these modern agents have been exclusively validated in
      specific tumor types. A major concern today is to determine whether the
      prescription of molecularly targeted therapies based on tumor molecular
      abnormalities, independently of primary tumor location and histology, would
      improve the outcome of cancer patients. This new paradigm requires prospective
      validation before being implemented in clinical practice. In this paper, we will
      first review different designs, including observational cohorts, as well as
      nonrandomized and randomized clinical trials, that have been recently proposed to
      evaluate the relevance of this approach, and further discuss their advantages and
      drawbacks. The design of the SHIVA trial, a randomized proof-of-concept phase II
      trial comparing therapy based on tumor molecular profiling versus conventional
      therapy in patients with refractory cancer will be detailed. Finally, we will
      discuss the multiple challenges associated with the implementation of
      personalized medicine in oncology, as well as perspectives for the future.

PMID- 23161022
TI  - Injection-molded capsular device for oral pulsatile release: development of a
      novel mold.
AB  - The development of a purposely devised mold and a newly set up injection molding
      (IM) manufacturing process was undertaken to prepare swellable/erodible
      hydroxypropyl cellulose-based capsular containers. When orally administered, such
      devices would be intended to achieve pulsatile and/or colonic time-dependent
      delivery of drugs. An in-depth evaluation of thermal, rheological, and mechanical
      characteristics of melt formulations/molded items made of the selected polymer
      (Klucel(r) LF) with increasing amounts of plasticizer (polyethylene glycol 1500,
      5%-15% by weight) was preliminarily carried out. On the basis of the results
      obtained, a new mold was designed that allowed, through an automatic
      manufacturing cycle of 5 s duration, matching cap and body items to be prepared.
      These were subsequently filled and coupled to give a closed device of constant
      600 MUm thickness. As compared with previous IM systems having the same
      composition, such capsules showed improved closure mechanism, technological
      properties, especially in terms of reproducibility of the shell thickness, and
      release performance. Moreover, the ability of the capsular container to impart a
      constant lag phase before the liberation of the contents was demonstrated
      irrespective of the conveyed formulation.

PMID- 23161019
TI  - Current understanding of HOG-MAPK pathway in Aspergillus fumigatus.
AB  - Aspergillus fumigatus is an important opportunistic fungal pathogen that causes
      lethal systemic invasive aspergillosis. It must be able to adapt to stress in the
      microenvironment during host invasion and systemic spread. The high-osmolarity
      glycerol (HOG) mitogen-activated protein kinase (MAPK) signaling pathway is a key
      element that controls adaptation to environmental stress. It plays a critical
      role in the virulence of several fungal pathogens. In this review, we summarize
      the current knowledge about the functions of different components of the HOG-MAPK
      pathway in A. fumigatus through mutant analysis or inferences from the genome
      annotation, focusing on their roles in adaptation to stress, regulation of
      infection-related morphogenesis, and effect on virulence. We also briefly compare
      the functions of the HOG pathway in A. fumigatus with those in the model fungi
      Saccharomyces cerevisiae and Aspergillus nidulans as well as several other human
      and plant pathogens including Candida albicans, Cryptococcus neoformans, and
      Magnaporthe oryzae. The genes described in this review mainly include tcsB, fos1,
      skn7, sho1, pbs2, and sakA whose deletion mutants have already been established
      in A. fumigatus. Among them, fos1 has been considered a virulence factor in A.
      fumigatus, indicating that components of the HOG pathway may be suitable as
      targets for developing new fungicides. However, quite a few of the genes of this
      pathway, such as sskA (ssk1), sskB, steC, and downstream regulator genes, are not
      well characterized. System biology approaches may contribute to a more
      comprehensive understanding of HOG pathway functions with dynamic details.

PMID- 23161021
TI  - High expression of epithelial cellular adhesion molecule in peritoneal metastasis
      of gastric cancer.
AB  - Intraperitoneally administrated epithelial cellular adhesion molecule (EpCAM)
      monoclonal antibody is a therapeutic agent in patients with malignant effusion in
      several types of carcinoma. However, the role of EpCAM in peritoneal metastasis
      (PM) lesions and primary lesions of gastric cancer (GC) is still unclear.
      Therefore, in this study, we investigated EpCAM expression in GC patients with
      PM. We investigated the expression of EpCAM in 35PM lesions and 104 biopsy
      samples as primary lesions. Immunohistochemical staining was performed using the
      Ventana Benchmark XT (Roche Diagnostics) system. EpCAM expression was evaluated
      by calculating the total immunostaining score, which is the product of the
      proportion score and the intensity score. Overexpression was defined as a total
      score greater than 4. All PM specimens showed overexpression of EpCAM, and GC
      cells in both the surface layer and the deep layer of the PM showed a high
      expression of EpCAM. Meanwhile, in the biopsy sample, the expression of EpCAM
      ranged from none to strong. The EpCAM score results for PM specimens and biopsy
      samples were 11.0 +/- 2.0 and 6.9 +/- 3.9, respectively. The difference between
      the scores was statistically significant (P < 0.05). The intraperitoneally
      administrated EpCAM antibody might have a anti-cancer effect in PM lesions of GC.
      Additionally, it can be assumed that only GC cells which express a high level of
      EpCAM might metastasize to the peritoneum.

PMID- 23161023
TI  - In vitro antiviral activity of dermaseptin S(4)  and derivatives from amphibian
      skin against herpes simplex virus type 2.
AB  - Herpes simplex virus (HSV) infections have become a public health problem
      worldwide. The emergence of acyclovir-resistant viral strains and the failure of
      vaccination to prevent herpetic infections have prompted the search for new
      antiviral drugs. Accordingly, the present study was undertaken to synthesize
      chemically and evaluate Dermaseptin S(4) (S(4)), an anti-microbial peptide
      derived from amphibian skin, and its derivatives in terms of anti-herpetic
      activity. The effects of biochemical modifications on their antimicrobial
      potential were also investigated. The peptides were incubated together with HSV-2
      on target cells under various conditions, and the antiviral effects were examined
      via a cell metabolic labeling method. The findings revealed that DS(4)
      derivatives elicited concentration-dependent antiviral activity at micromole
      concentrations. The biochemical modifications of S(4) allowed for the reduction
      of peptide cytotoxicity without altering antiviral activity. Dermaseptins were
      added at different times during the viral cycle to investigate the mode of
      antiviral action. At the highest non-cytotoxic concentrations, most of the tested
      derivatives were noted to exhibit high antiviral activity particularly when pre
      incubated with free herpes viruses prior to infection. Among these peptides,
      K(4)K(20)S(4) exhibited the highest antiviral activity against HSV-2 sensitive
      and resistant strains. Interestingly, the antiviral activity of K(4)K(20)S(4) was
      effective on both acyclovir-resistant and -sensitive viruses. The findings
      indicate that K(4)K(20)S(4) can be considered a promising candidate for future
      application as a therapeutic virucidal agent for the treatment of herpes viruses.

PMID- 23161024
TI  - Chlorobaculum tepidum TLS displays a complex transcriptional response to sulfide
      addition.
AB  - Chlorobaculum tepidum is a green sulfur bacterium (GSB) that is a model system
      for phototrophic sulfur oxidation. Despite over 2 decades of research,
      conspicuous gaps exist in our understanding of its electron donor metabolism and
      regulation. RNA sequencing (RNA-seq) was used to provide a global picture of the
      C. tepidum transcriptome during growth on thiosulfate as the sole electron donor
      and at time points following the addition of sulfide to such a culture. Following
      sulfide addition, 121 to 150 protein-coding genes displayed significant changes
      in expression depending upon the time point. These changes included a rapid
      decrease in expression of thiosulfate and elemental sulfur oxidation genes. Genes
      and gene loci with increased expression included CT1087, encoding a
      sulfide:quinone oxidoreductase required for growth in high sulfide
      concentrations; a polysulfide reductase-like complex operon, psrABC (CT0496 to
      CT0494); and, surprisingly, a large cluster of genes involved in iron
      acquisition. Finally, two genes that are conserved as a cassette in anaerobic
      bacteria and archaea, CT1276 and CT1277, displayed a strong increase in
      expression. The CT1277 gene product contains a DNA-binding domain, suggesting a
      role for it in sulfide-dependent gene expression changes.

PMID- 23161025
TI  - Brucella melitensis MucR, an orthologue of Sinorhizobium meliloti MucR, is
      involved in resistance to oxidative, detergent, and saline stresses and cell
      envelope modifications.
AB  - Brucella spp. and Sinorhizobium meliloti are alphaproteobacteria that share not
      only an intracellular lifestyle in their respective hosts, but also a crucial
      requirement for cell envelope components and their timely regulation for a
      successful infectious cycle. Here, we report the characterization of Brucella
      melitensis mucR, which encodes a zinc finger transcriptional regulator that has
      previously been shown to be involved in cellular and mouse infections at early
      time points. MucR modulates the surface properties of the bacteria and their
      resistance to environmental stresses (i.e., oxidative stress, cationic peptide,
      and detergents). We show that B. melitensis mucR is a functional orthologue of S.
      meliloti mucR, because it was able to restore the production of succinoglycan in
      an S. meliloti mucR mutant, as detected by calcofluor staining. Similar to S.
      meliloti MucR, B. melitensis MucR also represses its own transcription and
      flagellar gene expression via the flagellar master regulator ftcR. More
      surprisingly, we demonstrate that MucR regulates a lipid A core modification in
      B. melitensis. These changes could account for the attenuated virulence of a mucR
      mutant. These data reinforce the idea that there is a common conserved circuitry
      between plant symbionts and animal pathogens that regulates the relationship they
      have with their hosts.

PMID- 23161026
TI  - Coordinated cyclic-di-GMP repression of Salmonella motility through YcgR and
      cellulose.
AB  - Cyclic di-GMP (c-di-GMP) is a secondary messenger that controls a variety of
      cellular processes, including the switch between a biofilm and a planktonic
      bacterial lifestyle. This nucleotide binds to cellular effectors in order to
      exert its regulatory functions. In Salmonella, two proteins, BcsA and YcgR, both
      of them containing a c-di-GMP binding PilZ domain, are the only known c-di-GMP
      receptors. BcsA, upon c-di-GMP binding, synthesizes cellulose, the main
      exopolysaccharide of the biofilm matrix. YcgR is dedicated to c-di-GMP-dependent
      inhibition of motility through its interaction with flagellar motor proteins.
      However, previous evidences indicate that in the absence of YcgR, there is still
      an additional element that mediates motility impairment under high c-di-GMP
      levels. Here we have uncovered that cellulose per se is the factor that further
      promotes inhibition of bacterial motility once high c-di-GMP contents drive the
      activation of a sessile lifestyle. Inactivation of different genes of the bcsABZC
      operon, mutation of the conserved residues in the RxxxR motif of the BcsA PilZ
      domain, or degradation of the cellulose produced by BcsA rescued the motility
      defect of DeltaycgR strains in which high c-di-GMP levels were reached through
      the overexpression of diguanylate cyclases. High c-di-GMP levels provoked
      cellulose accumulation around cells that impeded flagellar rotation, probably by
      means of steric hindrance, without affecting flagellum gene expression,
      exportation, or assembly. Our results highlight the relevance of cellulose in
      Salmonella lifestyle switching as an architectural element that is both essential
      for biofilm development and required, in collaboration with YcgR, for complete
      motility inhibition.

PMID- 23161027
TI  - Partial complementation of Sinorhizobium meliloti bacA mutant phenotypes by the
      Mycobacterium tuberculosis BacA protein.
AB  - The Sinorhizobium meliloti BacA ABC transporter protein plays an important role
      in its nodulating symbiosis with the legume alfalfa (Medicago sativa). The
      Mycobacterium tuberculosis BacA homolog was found to be important for the
      maintenance of chronic murine infections, yet its in vivo function is unknown. In
      the legume plant as well as in the mammalian host, bacteria encounter host
      antimicrobial peptides (AMPs). We found that the M. tuberculosis BacA protein was
      able to partially complement the symbiotic defect of an S. meliloti BacA
      deficient mutant on alfalfa plants and to protect this mutant in vitro from the
      antimicrobial activity of a synthetic legume peptide, NCR247, and a recombinant
      human beta-defensin 2 (HBD2). This finding was also confirmed using an M.
      tuberculosis insertion mutant. Furthermore, M. tuberculosis BacA-mediated
      protection of the legume symbiont S. meliloti against legume defensins as well as
      HBD2 is dependent on its attached ATPase domain. In addition, we show that M.
      tuberculosis BacA mediates peptide uptake of the truncated bovine AMP, Bac7(1
      16). This process required a functional ATPase domain. We therefore suggest that
      M. tuberculosis BacA is important for the transport of peptides across the
      cytoplasmic membrane and is part of a complete ABC transporter. Hence, BacA
      mediated protection against host AMPs might be important for the maintenance of
      latent infections.

PMID- 23161028
TI  - Interaction between FliJ and FlhA, components of the bacterial flagellar type III
      export apparatus.
AB  - A soluble protein, FliJ, along with a membrane protein, FlhA, plays a role in the
      energy coupling mechanism for bacterial flagellar protein export. The water
      soluble FliH(X)-FliI(6) ATPase ring complex allows FliJ to efficiently interact
      with FlhA. However, the FlhA binding site of FliJ remains unknown. Here, we
      carried out genetic analysis of a region formed by well-conserved residues-Gln38,
      Leu42, Tyr45, Tyr49, Phe72, Leu76, Ala79, and His83-of FliJ. A structural model
      of the FliI(6)-FliJ ring complex suggests that they extend out of the FliI(6)
      ring. Glutathione S-transferase (GST)-FliJ inhibited the motility of and
      flagellar protein export by both wild-type cells and a fliH-fliI flhB(P28T)
      bypass mutant. Pulldown assays revealed that the reduced export activity of the
      export apparatus results from the binding of GST-FliJ to FlhA. The F72A and L76A
      mutations of FliJ significantly reduced the binding affinity of FliJ for FlhA,
      thereby suppressing the inhibitory effect of GST-FliJ on the protein export. The
      F72A and L76A mutations were tolerated in the presence of FliH and FliI but
      considerably reduced motility in their absence. These two mutations affected
      neither the interaction with FliI nor the FliI ATPase activity. These results
      suggest that FliJ(F72A) and FliJ(L76A) require the support of FliH and FliI to
      exert their export function. Therefore, we propose that the well-conserved
      surface of FliJ is involved in the interaction with FlhA.

PMID- 23161029
TI  - Distinct roles of highly conserved charged residues at the MotA-FliG interface in
      bacterial flagellar motor rotation.
AB  - Electrostatic interactions between the stator protein MotA and the rotor protein
      FliG are important for bacterial flagellar motor rotation. Arg90 and Glu98 of
      MotA are required not only for torque generation but also for stator assembly
      around the rotor, but their actual roles remain unknown. Here we analyzed the
      roles of functionally important charged residues at the MotA-FliG interface in
      motor performance. About 75% of the motA(R90E) cells and 45% of the motA(E98K)
      cells showed no fluorescent spots of green fluorescent protein (GFP)-MotB,
      indicating reduced efficiency of stator assembly around the rotor. The
      FliG(D289K) and FliG(R281V) mutations, which restore the motility of the
      motA(R90E) and motA(E98K) mutants, respectively, showed reduced numbers and
      intensity of GFP-MotB spots as well. The FliG(D289K) mutation significantly
      recovered the localization of GFP-MotB to the motor in the motA(R90E) mutant,
      whereas the FliG(R281V) mutation did not recover the GFP-MotB localization in the
      motA(E98K) mutant. These results suggest that the MotA-Arg90-FliG-Asp289
      interaction is critical for the proper positioning of the stators around the
      rotor, whereas the MotA-Glu98-FliG-Arg281 interaction is more important for
      torque generation.

PMID- 23161030
TI  - A novel inducer of Roseobacter motility is also a disruptor of algal symbiosis.
AB  - Silicibacter sp. strain TM1040, a member of the Roseobacter clade, forms a
      symbiosis with unicellular phytoplankton, which is inextricably linked to the
      biphasic "swim or stick" lifestyle of the bacteria. Mutations in flaC bias the
      population toward the motile phase. Renewed examination of the FlaC(-) strain
      (HG1016) uncovered that it is composed of two different cells: a pigmented type,
      PS01, and a nonpigmented cell, PS02, each of which has an identical mutation in
      flaC. While monocultures of PS01 and PS02 had few motile cells (0.6 and 6%,
      respectively), coculturing the two strains resulted in a 10-fold increase in the
      number of motile cells. Cell-free supernatants from coculture or wild-type cells
      were fully capable of restoring motility to PS01 and PS02, which was due to
      increased fliC3 (flagellin) transcription, FliC3 protein levels per cell, and
      flagella synthesis. The motility-inducing compound has an estimated mass of 226
      Da, as determined by mass spectrometry, and is referred to as Roseobacter
      Motility Inducer (RMI). Mutations affecting genes involved in phenyl acetic acid
      synthesis significantly reduced RMI, while defects in tropodithietic acid (TDA)
      synthesis had marginal or no effect on RMI. RMI biosynthesis is induced by p
      coumaric acid, a product of algal lignin degradation. When added to algal
      cultures, RMI caused loss of motility, cell enlargement, and vacuolization in the
      algal cells. RMI is a new member of the roseobacticide family of troponoid
      compounds whose activities affect roseobacters, by shifting their population
      toward motility, as well as their phytoplankton hosts, through an algicidal
      effect.

PMID- 23161031
TI  - Domain analysis of ArcS, the hybrid sensor kinase of the Shewanella oneidensis MR
      1 Arc two-component system, reveals functional differentiation of its two
      receiver domains.
AB  - In all species of the genus Shewanella, the redox-sensing Arc two-component
      system consists of the response regulator ArcA, the sensor kinase ArcS, and the
      separate phosphotransfer protein HptA. Compared to its counterpart ArcB in
      Escherichia coli, ArcS has a significantly different domain structure.
      Resequencing and reannotation revealed that in the N-terminal part, ArcS
      possesses a periplasmic CaChe-sensing domain bracketed by two transmembrane
      domains and, moreover, that ArcS has two cytoplasmic PAS-sensing domains and two
      receiver domains, compared to a single one of each in ArcB. Here, we used a
      combination of in vitro phosphotransfer studies on purified proteins and
      phenotypic in vivo mutant analysis to determine the roles of the different
      domains in ArcS function. The analysis revealed that phosphotransfer occurs from
      and toward the response regulator ArcA and involves mainly the C-terminal RecII
      domain. However, RecI also can receive a phosphate from HptA. In addition, the
      PAS-II domain, located upstream of the histidine kinase domain, is crucial for
      function. The results support a model in which phosphorylation of RecI stimulates
      histidine kinase activity of ArcS in order to maintain an appropriate level of
      phosphorylated ArcA according to environmental conditions. In addition, the study
      reveals some fundamental mechanistic differences between ArcS/HptA and ArcB with
      respect to signal perception and phosphotransfer despite functional conservation
      of the Arc system in Shewanella and E. coli.

PMID- 23161033
TI  - The patient with chronic ischemic heart disease. Role of ranolazine in the
      management of stable angina.
AB  - Ischemic heart disease (IHD) is a major cause of death in Western Countries and
      accounts for very high costs worldwide. In this review we discussed the
      pathogenesis, symptoms, diagnosis, prognosis and management of chronic IHD. In
      particular, we discussed about the percutaneous coronary interventions and
      coronary artery bypass grafting, as well as to clinical trials that evaluated the
      advantages of one approach versus another.  Pharmacological treatment is among
      major objectives of the review and for each class of therapeutic agents an
      evaluation of well-conducted clinical trials is provided. The most important drug
      classes in IHD treatment are betablockers, calcium channel blockers, nitrates,
      antiplatelet agents, and ACE-inhibitors. In addition to these agents, also new
      treatment options are evaluated in patients with stable IHD. Ranolazine, in
      particular, is a innovative anti-anginal drug with a great successful in the
      management of patients with refractory angina. A pharmacological as well as
      clinical profile of this drug is provided.

PMID- 23161032
TI  - Identification and characterization of a high-affinity choline uptake system of
      Brucella abortus.
AB  - Phosphatidylcholine (PC), a common phospholipid of the eukaryotic cell membrane,
      is present in the cell envelope of the intracellular pathogen Brucella abortus,
      the etiological agent of bovine brucellosis. In this pathogen, the biosynthesis
      of PC proceeds mainly through the phosphatidylcholine synthase pathway; hence, it
      relies on the presence of choline in the milieu. These observations imply that B.
      abortus encodes an as-yet-unknown choline uptake system. Taking advantage of the
      requirement of choline uptake for PC synthesis, we devised a method that allowed
      us to identify a homologue of ChoX, the high-affinity periplasmic binding protein
      of the ABC transporter ChoXWV. Disruption of the choX gene completely abrogated
      PC synthesis at low choline concentrations in the medium, thus indicating that it
      is a high-affinity transporter needed for PC synthesis via the PC synthase (PCS)
      pathway. However, the synthesis of PC was restored when the mutant was incubated
      in media with higher choline concentrations, suggesting the presence of an
      alternative low-affinity choline uptake activity. By means of a fluorescence
      based equilibrium-binding assay and using the kinetics of radiolabeled choline
      uptake, we show that ChoX binds choline with an extremely high affinity, and we
      also demonstrate that its activity is inhibited by increasing choline
      concentrations. Cell infection assays indicate that ChoX activity is required
      during the first phase of B. abortus intracellular traffic, suggesting that
      choline concentrations in the early and intermediate Brucella-containing vacuoles
      are limited. Altogether, these results suggest that choline transport and PC
      synthesis are strictly regulated in B. abortus.

PMID- 23161034
TI  - Elevated uric acid and functional mitral regurgitation in dilated cardiomyopathy.
AB  - BACKGROUND: Recent findings suggest that there is a close relationship between
      chronic heart failure and uric acid. AIMS: The aim of the study was to assess
      whether increased uric acid levels in patients with dilated cardiomyopathy might
      correlate with the degree of functional mitral regurgitation (MR). MATERIALS AND
      METHODS: Sixty two consecutive patients diagnosed with dilated cardiomyopathy
      were included in the study. The patients were classified according to severity of
      functional MR into two groups: mild-moderate functional MR (ERO < 0.2 cm2) and
      severe functional MR. RESULTS: The patients with severe functional MR had
      significantly higher serum uric acid levels compared to patients without severe
      functional MR (6.34 +/- 1.61 mg/dL vs 5.43 +/- 1.17 mg/dL respectively, p =
      0.012). Furthermore, tenting area, an important predictor of functional MR
      severity, was moderately correlated with the serum uric acid levels (r = 0.351, p
      = 0.005). It was also shown that the serum uric acid concentrations were
      inversely correlated with left ventricular (LV) ejection fraction, and positively
      correlated with LV volumes. There was also a significant relation between the
      serum uric acid and left atrial volumes and also brain natriuretic peptide (BNP)
      levels. CONCLUSIONS: In conclusion, this study demonstrates that elevated serum
      uric acid levels in patients with dilated cardiomyopathy are correlated with the
      severity of functional MR and echocardiographic volume indices.

PMID- 23161035
TI  - Same effect of sublingual and oral captopril in hypertensive crisis.
AB  - BACKGROUND AND OBJECTIVES: Hypertensive crisis is a condition characterized by
      rapid and inappropriate symptomatic elevation of blood pressure (BP) that is
      commonly seen in Emergency Departments. Oral or sublingual captopril is commonly
      used in the Emergency Departments. The unpleasant taste of the sublingual drugs
      causes uncomfortable condition to the patient. Studies showing no difference
      between oral and sublingual captopril has been ignored so far. Herein we compared
      the oral and sublingual captopril efficiency in the hypertensive urgencies.
      MATERIALS AND METHODS: In this retrospective observational study, 71 patients
      admitted with hypertensive urgency to Emergency Departments of two hospitals in
      2011 whose blood pressure were recorded before captopril administration and blood
      pressure were recorded after captopril administration at 0-5-15-30-45-60 minutes
      were included the study. The reductions of the blood pressure of oral and
      sublingual captopril groups were compared. RESULTS: There were 28 patients at
      oral and 43 at sublingual captopril group. The mean age +/- SD was 58.13 +/- 8.66
      years and 41 (57.7%) patients were female. The most common complaints were
      headache, nausea/vomiting and weakness. 65 (91.5%) patients were using
      antihypertensive drugs before admitted to hospital. The blood pressure at 0, 5,
      15, 30, 45 and 60th minutes of therapy didn't show any difference between oral
      and sublingual captopril use. CONCLUSIONS: There was any difference between oral
      and sublingual captopril efficiency to control of hypertension in patient with
      hypertensive urgency. For a more comfortable treatment, oral captopril may be a
      more convenient choice in the hypertensive urgencies.

PMID- 23161036
TI  - Can peripheral arterial disease be early screened for in a podiatric setting? A
      preliminary study in a cohort of asymptomatic adults.
AB  - BACKGROUND: Peripheral arterial disease (PAD) is a strong marker of
      cardiovascular disease but remains an under-diagnosed problem. Moreover, PAD
      frequently leads to foot problems requiring particular care and surveillance.
      AIM: The aims of this study were (1) to determine the prevalence of undiagnosed
      PAD in a cohort of asymptomatic subjects referred to a podiatric clinic and (2)
      to evaluate whether a four-item form assessing medical history for the presence
      of cardiovascular risk factors could identify subjects at high risk for
      asymptomatic PAD. PATIENTS AND METHODS: This study included 717 consecutive
      subjects (121 males, age 50.9+/-13.9 y) referring to a podiatric clinic who were
      asymptomatic for PAD and free of cardiovascular disease. The ankle brachial index
      (ABI) was measured in all subjects. Each subject also completed a self
      administered form to identify cardiovascular risk factors. RESULTS: Among the
      entire cohort, the prevalence of PAD was 8.3% in males and 1.2% in females. Three
      subgroups were identified according to the number of risk factors reported (no
      risk factors, one risk factor, and two or more risk factors), and the prevalence
      of PAD differed between each subgroup (0.2%, 3.2%, and 18.9%, respectively; p <
      0.001). CONCLUSIONS: In an unselected cohort of subjects referring to a podiatric
      clinic, who were asymptomatic for PAD and free from cardiovascular diseases, a
      remarkable prevalence of PAD was found among subjects reporting a minimum of two
      cardiovascular risk factors. In a podiatric setting, screening with a self
      administered form for the presence of cardiovascular risk factors might lead to
      an early diagnosis of PAD.

PMID- 23161037
TI  - Current therapeutic strategy in Alzheimer's disease.
AB  - Alzheimer's disease (AD) is a chronic, progressive, neurodegenerative disorder
      that places a substantial burden on patients, their families, and society.
      Alzheimer's disease (AD) is the sixth leading cause of all deaths in the United
      States, and the fifth leading cause of death in Americans aged 65 and older.
      During the past years, several agents have been approved that enhance cognition
      and global function of AD patients, and recent advances in understanding AD
      pathogenesis has led to the development of numerous compounds that might modify
      the disease process. A wide array of antiamyloid and neuroprotective therapeutic
      approaches are under investigation on the basis of the hypothesis that amyloid
      beta (Abeta) protein plays a pivotal role in disease onset and progression and
      that secondary consequences of Abeta generation and deposition, including tau
      hyperphosphorylation and neurofibrillary tangle formation, oxidation,
      inflammation, and excitotoxicity, contribute to the disease process.
      Interventions in these processes with agents that reduce amyloid production,
      limit aggregation, or increase removal or vaccination and immunization might
      block the cascade of events comprising AD pathogenesis. Reducing tau
      hyperphosphorylation, limiting oxidation and excitotoxicity, and controlling
      inflammation might be beneficial disease-modifying strategies. Potentially
      neuroprotective and restorative treatments such as neurotrophins, neurotrophic
      factor enhancers, and stem cell-related approaches are also under investigation. 

PMID- 23161038
TI  - Oral L-arginine supplementation in patients with mild arterial hypertension and
      its effect on plasma level of asymmetric dimethylarginine, L-citruline, L
      arginine and antioxidant status.
AB  - BACKGROUND: Potential role of L-arginine supplementation as a new effective
      strategy of improving endothelial function in patients with hypertension is
      recently under consideration. OBJECTIVE: To evaluate influence of 28-day oral
      supplementation of L-arginine on plasma level of asymmetric dimethylarginine
      (ADMA), L-citrulline, L-arginine and total antioxidant status (TAS), in patients
      with mild arterial hypertension. SUBJECTS AND METHODS: 54 participants (24 women
      and 30 men) were studied. Ambulatory blood pressure monitoring (ABPM) was used
      for allotting patients to either healthy control group (19 subjects) or
      hypertensive treatment group (35 patients). Patients were later randomized to
      either L-arginine (2 g tid or 4 g tid) or placebo. During 28 days of study on 5
      consecutive visits TAS, plasma level of ADMA, L-citrulline, and L-arginine were
      measured. RESULTS: In patients with mild hypertension treated with L-arginine
      significant increase in TAS and plasma level of arginine and citrulline was
      observed. Additionally plasma ADMA concentrations after 28 days of L-arginine
      supplementation significantly exceeded initial concentrations. CONCLUSIONS: L
      arginine supplementation increases plasma arginine, citrulline and TAS in
      patients with mild arterial hypertension. It confirms the thesis that augmented
      concentrations of L-arginine stimulate NO biosynthesis which leads to reduction
      of oxidative stress. Increase of ADMA plasma level after L-arginine
      supplementation confirms correlation between ADMA and L-arginine.

PMID- 23161039
TI  - Efficacy of scheduled time ketorolac administration compared to continuous
      infusion for post-operative pain after abdominal surgery.
AB  - BACKGROUND: Ketorolac tromethanime is a non steroidal anti inflammatory drug and
      its efficacy on acute pain control after abdominal surgery has been well
      documented. It has a rapid onset and it can be given both for intra operative and
      for post operative pain management. AIM: In this study we aimed to evaluate if
      there were any differences in relieving post operative pain when Ketorolac was
      administered with continuous infusion or if it was given at prearranged times.
      PATIENTS AND METHODS: 80 ASA I patients, scheduled for major gynecological
      surgery, were randomly assigned to 2 groups: group A patients were connected
      after surgical incision with a 24h analgesic infusor (2 ml/h) containing morphine
      (0.02 mg/kg/h) and Ketorolac (90 mg). Group B patients were connected after
      surgical incision with a 24h analgesic infusor (2 ml/h) containing morphine (0.02
      mg/kg/h) at first and Ketorolac was then given in bolus after surgical incision
      and then every 8 hours for the first 24 hours. Post-operative pain scores were
      assessed using the Visual Analogue Scale (VAS) every 8 hours for 24 h. For a VAS
      value greater than 6, patients received Tramadol 100 mg. RESULTS: Post-operative
      pain scores showed a better pain relief for patients in the group B. Furthermore,
      the requirements of rescue analgesic were less in the group B [Tramadol was used
      for only 8 patients] than in the group A [Tramadol was used for 31 patients]. No
      adverse effects were registered in both groups. <strong> CONCLUSIONS: </strong>
      For post-operative pain Ketorolac administration at prearranged times, every 8
      hours, offers greater benefits in respect to its continuous infusion.

PMID- 23161040
TI  - Effect of food restriction on reproductive-related genes and reproductive
      hormones in adult female rats.
AB  - OBJECTIVES: A number of factors involved in the control of energy balance and
      metabolism act as modulators of gonadal axis. Ghrelin, a peptide secreted from
      the stomach and hypothalamus, has emerged as an orexigenic food intake
      controlling signal acting upon hypothalamus. Recently, the potential reproductive
      role of ghrelin has received great attention. This study was designed to
      investigate the influence of food restriction and consequent metabolic hormone
      (ghrelin) on the level and gene expression of female reproductive hormones in
      adult rats. MATERIALS AND METHODS: To study the effect of chronic food
      restriction on ghrelin level in adult female rats and its relation to female
      reproductive hormones, 32 adult female Sprague Dawley rats divided into 4 groups:
      Group I (control group) comprised 8 rats fed ad libitum for 30 days, Group II,
      III and IV (food-restricted groups for 10, 20 and 30 days respectively) each
      consisted of 8 rats fed 50% of ad libitum intake determined by the amount of food
      consumed by the control group. RESULTS: Mean body weight of food restricted rats
      was observed to decrease during the period of the experiment. Food restriction
      produced significant increase of serum ghrelin with significant decrease of both
      gastric and hypothalamic ghrelin accompanied with significant increase in its
      gene expression in stomach and hypothalamus. Estradiol (E2), follicle-stimulating
      hormone (FSH) and luteinizing hormone (LH) levels showed significant decrease
      correlated with down-regulation of gonadotropins, cyclin-dependent kinase (cdc2),
      cyclin B and kisspeptin (Kiss1) genes in food restricted rats compared with
      control group. CONCLUSIONS: Ghrelin could be one of the hormones responsible for
      the suppression of female reproductive axis in case of negative energy balance.
      Thus, ghrelin may operate as an autocrine/paracrine regulator of ovarian
      function. Overall, ghrelin may represent an additional link between body weight
      homeostasis and reproductive function.

PMID- 23161041
TI  - Platelet glycoprotein IaC807T polymorphisms and ischemic stroke in young Chinese
      Han population.
AB  - OBJECTIVES: The objective of this study was to investigate the association
      between platelet glycoprotein (GP) Ia C807T polymorphisms and ischemic stroke in
      young Chinese Han Population. MATERIALS AND METHODS: We conducted a case-control
      study in 92 consecutive young (</= 50 years) first-ever hospitalized ischemic
      stroke inpatients and outpatients, 86 elder ischemic stroke control (> 50 years),
      and 160 age- and sex-matched healthy control. Genotyping of platelet GP Ia
      C807Tpolymorphisms was performed by polymerase chain reaction followed by
      sequencing nucleic acid with dideoxy chain-termination method and an ABI
      PRISM3100 (Perkin-Elmer Co) genetic analyzer. Student's t-test, chi-square test,
      and logistic regression modeling were used for data significance analyses.
      RESULTS: Hypertension and smoking were found to be the independent risk factors
      for ischemic stroke patients (aged </= 50 years), while hypertension, diabetes
      and smoking were the independent risk factors for ischemic stroke patients (aged
      > 50 years). There was no significant difference observed in the T allele
      frequency of GPIa C807T polymorphisms between young stroke patients and
      corresponding controls. CONCLUSIONS: These findings suggest that there is no role
      of GPIa C807T polymorphisms in the development of young first-ever ischemic
      stroke in Chinese Han Population.

PMID- 23161042
TI  - Fungal peritonitis in peritoneal dialysis: a 10 year retrospective analysis in a
      single center.
AB  - INTRODUCTION: Fungal peritonitis (FP) is a rare but serious complication in
      patients undergoing peritoneal dialysis (PD), and is associated with higher
      morbidity, mortality. We aimed to analyze the predisposing factors, etiological
      agents, outcome and treatment of FP in patients with PD. METHODOLOGY: We
      evaluated retrospectively all PD patients PD center between 2001 and 2011.
      Sixteen patients with FP were included into the study. RESULTS: The clinical
      records of 16 patients with FP among 355 patients were reviewed for the clinical
      and laboratory data. Among 506 episodes of PD-related peritonitis in 10 years, we
      identified 16 episodes of FP. Median PD duration was 36.7+/-22.2 months. In 87.5%
      of patients had one or more previous episode of bacterial peritonitis that were
      treated with multiple broad-spectrum antibiotics. FP was primary infection in
      five patients, whereas eleven patients experienced FP during the course of
      treatment of bacterial peritonitis. Six patients died due to the fungal infection
      whereas others were transferred to haemodialysis. CONCLUSIONS: Treatment of
      bacterial peritonitis with broad spectrum antibiotics was an important risk
      factor predisposing to the development of FP. The catheter removal and initiation
      of antifungal therapy as soon as possible are obligatory in episode of FP because
      it is responsible from high mortality rate.

PMID- 23161043
TI  - Research on the molecular mechanism of Seretide treatment to asthma disease.
AB  - INTRODUCTION: Asthma is one of the most common chronic diseases in children. It
      is attributable to complicated coactions between various genetic factors and
      environmental allergens. AIM: We attempt to unfold the mechanism of asthmatic
      disorder and research the molecular mechanism of Seretide on asthmatic disease.
      MATERIALS AND METHODS: Using the GSE31773 microarray datasets downloaded from
      Gene Expression Omnibus database, we first screened the differentially expressed
      genes between healthy control and asthmatic samples cells based on classical t
      test and false discovery rate < 0.05 as significant threshold. The underlying
      molecular mechanisms were investigated by Kyoto Encyclopedia of Genes and Genomes
      pathway enrichment analysis. In addition, the crosstalk network of pathways was
      also constructed. RESULTS: A total of 2011 differentially expressed genes were
      obtained by comparing asthmatic sample treated with Seretide and healthy
      controls. A total of 403 differentially expressed genes were collected between
      asthma samples untreated by Seretide and healthy sample controls. The enriched
      pathway of differentially expressed genes included signal transduction disorder
      (such as TGF-beta signaling pathway) and metabolism disorder (such as
      Phenylalanine metabolism). There were 27 pathway crosstalk pairs among 13
      pathways. CONCLUSIONS: Our findings will help to clarify the molecular mechanism
      of Seretide and offer advices for asthma pathogenesis, Seretide therapy and
      follow-up treatment.

PMID- 23161044
TI  - Serum levels of neopterin, tumor necrosis factor-alpha and Interleukin-6 in
      preeclampsia: relationship with disease severity.
AB  - AIM: There are many studies evaluating the role of inflammation in the
      pathogenesis of preeclampsia. However, little is known about the relationship
      between the severity of inflammation and the severity of preeclampsia due to
      insufficient of studies reporting this matter. To investigate the maternal serum
      concentrations of IL-6, TNF-alpha and Neopterin in patients with mild
      preeclampsia and severe preeclampsia and HELLP (hemolysis, elevated liver
      enzymes, low platelet count) syndrome in preeclampsia and determine their
      association with the severity of the disease. PATIENTS AND METHODS: Patients,
      hospitalized with the diagnosis of preeclampsia between October 2011 and March
      2012, were included in the study. The patients with preeclampsia were divided
      into three groups as mild preeclampsia, severe preeclampsia and HELLP syndrome.
      The control group was comprised of normotensive and uncomplicated pregnant women.
      The serum levels of IL-6, TNF-alpha and Neopterin (NEO) were determined, using
      enzyme-linked immunosorbent assay. Spearman's rank correlation tests were used
      for the correlations between the serum levels of inflammatory markers and the
      severity of preeclampsia. RESULTS: There was no observed significant difference
      among mean serum TNF-alpha and IL-6 levels of four groups (p > 0.05). The median
      serum concentration of NEO in subjects with mild preeclampsia of 14.1 nmol/L and
      severe preeclampsia of 14.8 nmol/L was significantly higher than that of 10.3
      nmol/L in normotensive controls (p = 0.013; p = 0.000 respectively). In addition,
      the median serum concentration of NEO was detected to be highest in subjects with
      HELLP syndrome. The serum levels of NEO was well correlated with the severity of
      preeclampsia (r = 0.533, p = 0.000). CONCLUSIONS: The serum levels of NEO, an
      important marker of cellular immunity, associated with severity of disease in
      patients with preeclampsia.

PMID- 23161045
TI  - XPD and XRCC1 gene polymorphism in patients with normal and abnormal cervical
      cytology by pap smear.
AB  - AIM: The purpose of the present study was to identify the role of abnormalities
      in DNA repair pathways by measuring the XPD and XRCC1 gene polymorphisms.
      MATERIALS AND METHODS: Thirty-five patients with abnormal cervical cytology
      (study group) and 10 women with normal cytology (control group) were included in
      the study. The polymorphisms of XRCC1 Arg194Trp, XRCC1 Arg399Gln and XPD
      Lys751Gln genes were investigated from the blood samples. RESULTS: There was no
      statistically significant difference in allele frequencies of XPD gene among the
      groups (p = 0.097), while XRCC1R399Q gene polymorphism was strikingly more
      frequent in the study group than that of control cases (p = 0.029). The
      prevalence of XRCC1R194W gene polymorphism on the other hand, was similar between
      the groups (p = 0.579). CONCLUSIONS: Patients with abnormal and normal cervical
      cytology have similar XPD gene polymorphism. However, the frequency of gene
      polymorphism in XRCC1 Arg 399 Gln codon was significantly higher in abnormal
      cervical cytology group.

PMID- 23161046
TI  - Tracheostomy in childhood:  new causes for an old strategy.
AB  - INTRODUCTION: A review of the available literature has shown that the
      indications, epidemiology, and complications for tracheostomies are changing, and
      that no definite guidelines have been established. In the 1970s, the most common
      indication for tracheostomies in children was acute inflammatory airway
      obstruction. Modern neonatal intensive care units (ICU) have turned long-term
      intubation into an alternative to a tracheostomy. Currently, long-term intubation
      has become the most important indication for tracheostomies in children. PATIENTS
      AND METHODS: We present our series involving tracheostomies performed in
      paediatric patients between 2004 and 2008 at our hospital. Sixteen patients
      underwent tracheostomies for respiratory failure and upper airway obstruction.
      RESULTS: The total complications rate was 37.5%. In children < 1 year of age, the
      complications rate was 25%, while in children > 1 year of age, the complications
      rate was 12.5%. CONCLUSIONS: Long-term intubation and its sequelae have now
      become one of the most important indications for tracheostomies in the paediatric
      age group.

PMID- 23161047
TI  - The effect of latanoprost and influence of changes in body position on patients
      with glaucoma and ocular hypertension.
AB  - BACKGROUND AND OBJECTIVES: Some patients have an elevation of intraocular
      pressure (IOP) in the supine position (IOPSP). It has been suggested that topical
      latanoprost 0.005% (LP) has an attenuating effect on these IOP elevations. The
      Authors report a simple procedure to evaluate the change in the IOPSP. This paper
      presents the results of the change in the IOPSP in normals, in patients with
      ocular hypertension (OH) and in patients with primary open angle glaucoma (POAG).
      The study also evaluates the effect of the addition of topical LP on those
      patients with an elevation of their IOPSP. PATIENTS AND METHODS: Part 1 evaluated
      the change in the IOPSP in the morning in 40 eyes of normals, 82 eyes in patients
      with OH and 77 eyes in patients with POAG. The IOP was measured before and after
      lying in the supine position (SP) for 90 minutes. In part 2 the patients with OH
      or POAG with an increase in their IOPSP were selected and the test was repeated
      again after the addition of topical LP. RESULTS: When compared with normals, the
      patients with OH and POAG had significantly greater IOPSP increases. The patients
      with POAG had significantly greater IOPSP increases than did those with OH. The
      addition of LP partially decreased but did not eliminate the IOP increases in the
      SP. CONCLUSIONS: Patients with OH and POAG have a larger increase in their IOPSP
      than do normals. The addition of topical LP partially decreased but did not
      totally eliminate these pressure increases.

PMID- 23161048
TI  - Secondary lipofilling after breast reconstruction with implants.
AB  - BACKGROUND: Several Authors have reported on the use of lipoinjection as a low
      risk and low-morbidity procedure that gives good results for the correction of
      soft-tissue defects. AIM: The purpose of this study was to review our caseload of
      fat grafting after breast reconstruction with prosthesis. PATIENTS AND METHODS:
      Between January 2008 and December 2011, 20 patients were treated for breast
      asymmetries with secondary autologous fat injection after nipple-sparing, skin
      sparing and skin-reducing mastectomies breast reconstruction in our Departments.
      Exclusion criteria was postoperative radiotherapy. In order to assess aesthetic
      satisfaction, patients and an independent plastic surgeon filled an evaluation
      form (VAS = 1-10) preoperatively one and six months after surgery. RESULTS: In
      postoperative days no major complications occurred. Donor sites looks completely
      healthy and no scars were evident. The average values of aesthetic satisfaction
      in patients (VAS) were 5.2 (range 3-7) preoperatively, 7.9 (range 5-9) one month
      post-operatively and 7.2 six months postoperatively (range 5-9). Values reported
      by the surgeon team were an average of 4.9 (range 4-6) preoperatively, 7.6 after
      one month (range 6-9) and 7.1 after six months (range 5-9). CONCLUSIONS: Acquired
      contour deformities of the reconstructed breast are relatively common and
      independent from the technique used. Therefore, they present a frequent
      therapeutic challenge to reconstructive surgeons. Lipomodelling offers an "easy
      to perform" and predictable cosmetic solution to these patients. An objective
      examination of aesthetic results, in addition to our clinical analysis shows a
      significant improvement of cosmetic outcomes; moreover, all patients were
      satisfied for their final appearance.

PMID- 23161049
TI  - The impact of osteotomy technique for corticotomy-assisted orthodontic treatment
      (CAOT) on oral health-related quality of life.
AB  - BACKGROUND: Corticotomy in accelerating orthodontic tooth movement, also defined
      as corticotomy-assisted orthodontic treatment (CAOT), is a promising technique
      that recently had many applications in orthodontics. AIM: The purpose of this
      study was to compare the use of piezoelectric surgery and conventional rotatory
      osteotomy technique for CAOT, determining the duration of surgery and oral health
      related quality of life (OHRQoL). PATIENTS AND METHODS: CAOT was performed in a
      sample of subjects, randomly choosing piezoelectric surgery (PS Group) or
      conventional rotary osteotomy technique (RT Group). The duration of surgery was
      recorded and the oral health-related quality of life evaluated using the short
      form Oral Health Impact Profile (OHIP-14) preoperatively, 3 and 7 days after
      surgery. t-test and Cronbach's alpha were used for statistical analysis. RESULTS:
      12 patients (mean age 14; range: 13-17) were enrolled. The time needed to
      complete the osteotomy cuts was greater (p = 0.1) for the piezoelectric surgery
      group (mean 34.3 minutes; range 35.3-32.6) than for the rotator group(mean 28.2
      minutes; range 27.1-29.2). Oral health-related quality of life deteriorated from
      baseline (OHIP-14 mean: 6.33) to first follow-up, 3 day after surgery, in both
      groups (PS Group: 22.67 OHIP-14; RT Group: 21.33 OHIP-14). At 7 days follow-up
      there was a nearly complete recovery of the original OHIP-14 values , even faster
      with the conventional rotary osteotomy technique; however, no statistically
      significant differences were recorded between the two methods (p = 0.35).
      Cronbach's alpha values indicated an excellent internal consistency reliability.
      CONCLUSIONS: In clinical decision-making regarding the use of corticotomy
      assisted orthodontic treatment, it should be aware of the expected decrease in
      oral health-related quality of life both using piezoelectric surgery or rotary
      osteotomy technique. In addition, the piezoelectric osteotomy requires a longer
      surgical time.

PMID- 23161050
TI  - Bisphosphonate-related osteonecrosis of the jaw (BRONJ): 5 year experience in the
      treatment of 131 cases with ozone therapy.
AB  - BACKGROUND: Bisphosphonate-Related Osteonecrosis of the Jaw (BRONJ) are the
      result of the assumption of such drugs. The most widely used molecules are
      pamidronate and zoledronic acid, which are pyrophosphate analogues and are
      usually given to patient with bone remodelling diseases. International literature
      reports showed an association between this therapy and avascular necrosis, thus
      leading to review the guidelines for their administer. AIM: The authors present
      their protocol based upon medical treatment, antibiotic and antimycotic, together
      with minimally invasive surgery and ozone therapy developed after a 5 year
      experience to assess the viability of this treatment. MATERIALS AND METHODS: In
      the last years researchers studied treatment protocols, both medical and
      surgical, for the management of BRONJ. Among these Ozone therapy is being adopted
      by several centers. From February 2004 and December 2010 a total number of 131
      patients affected by BRONJ have been observed. Collected data include patients'
      age at the time of disorders, gender, presenting signs and symptoms, primary
      diagnosis, type and characteristics of the treatment performed, radiological
      findings and post-treatment results. CONCLUSIONS: At the present time there are
      no major guidelines in international literature for the treatment of BRONJ, the
      Authors then propose a therapeutic protocol based upon minimally invasive
      surgery, antibiotic and anti mycotic therapy with the adoption of ozone as
      regenerating factor for tissues. In 90% of the cases the results confirmed the
      procedure with successful outcomes.

PMID- 23161051
TI  - Complete atrioventricular block caused by mad honey intoxication.
AB  - The honey produced by the bees fed on Rhododendron family plants containing
      grayanotoxin is known as mad honey in our country. This intoxication is seen
      rarely. However, it may lead life-threatening hemoinstability mentioned above and
      may be confused with various diseases. For these reasons the exact diagnosis and
      treatment of this intoxication seems very important. We aim to describe a case
      admitted to the Emergency Department in consequence of mad honey intoxication and
      treated and discharged after hypotension and complete atrioventricular block
      development.

PMID- 23161052
TI  - Trigonella and it's rapidly emerging anti-neoplastic effects.

PMID- 23161054
TI  - Application of ionic liquid as additive in determination of three beta-agonists
      by capillary electrophoresis with amperometric detection.
AB  - CE coupled with amperometric detection method was developed using ionic liquid 1
      ethyl-3-methylimidazolium tetrafluoroborate (EMImBF(4)) as additive for the
      simultaneous detection of clenbuterol (CLB), terbutaline (TER), and ractopamine
      (RAC) in feed. The effects of detection potential, concentration of EMImBF(4),
      pH, and concentration of the running buffer, separation voltage as well as
      injection time on the separation and detection of these three beta-agonists were
      investigated in detail. Under the optimum conditions: the detection potential at
      1.05 V, 50 mmol/L Tris-HAc at pH 8.0 with 0.6% (v/v) EMImBF(4), electrokinetic
      injection 6 s at 16 kV and separation voltage at 16 kV, a baseline separation for
      these three analytes could be achieved within 11 min. Introduction of EMImBF(4)
      into the running buffer resulted in significant improvement in separation
      selectivity and enhancement in peak currents for those beta-agonists, especially
      for TER and RAC, which could not be separated in the running buffer without
      additive. The method exhibited wide linear range with LOD (S/N = 3) of 2, 1, and
      2 nmol/L for CLB, TER, and RAC, respectively. The precision was determined in
      both intraday (n = 5) and interday (n = 3) assays, and the RSDs for both
      migration time and peak current were less than 6%. The proposed method was also
      applied to analyze beta-agonists in feed sample.

PMID- 23161053
TI  - TNFAIP3 gene polymorphisms confer risk for Behcet's disease in a Chinese Han
      population.
AB  - The tumor necrosis factor alpha-inducible protein 3 (TNFAIP3) gene polymorphisms
      have recently been reported to be associated with the susceptibility to several
      immune-related diseases. This study was performed to evaluate the potential
      association of TNFAIP3 polymorphisms with Behcet's disease (BD) in a Chinese Han
      population. Five single-nucleotide polymorphisms (SNPs), rs10499194, rs610604,
      rs7753873, rs5029928, and rs9494885 of TNFAIP3 were genotyped in 722 BD patients
      and 1,415 healthy controls using a PCR-restriction fragment length polymorphism
      assay. Allele and genotype frequencies were compared between patients and
      controls using the chi (2) test. The results showed a significantly increased
      prevalence of the rs9494885 TC genotype and C allele in BD patients compared with
      controls (Bonferroni corrected p (p (c)) = 1.83 * 10(-10), odds ratio (OR) [95%
      CI] 2.03 [1.65-2.49]; p (c) = 8.35 * 10(-10), OR [95% CI] 1.81 [1.51-2.18],
      respectively).The frequency of the TT genotype and T allele of rs9494885 was
      markedly lower in BD patients than that in controls (p (c) = 1.23 * 10(-10), OR
      [95% CI] 0.50 [0.40-0.61]; p (c) = 8.35 * 10(-10), OR [95% CI] 0.55 [0.46-0.66],
      respectively). For rs10499194, a higher frequency of the CC genotype (p (c) =
      0.015, OR [95% CI] 1.96 [1.30-2.97]) and C allele (p (c) = 0.005, OR [95% CI]
      1.92 [1.28-2.90]), and a lower frequency of the TC genotype (p (c) = 0.015, OR
      [95% CI] 0.51 [0.34-0.77]) and T allele (p (c) = 0.005, OR [95% CI] 0.52 [0.35
      2.97]) were found in BD patients. Concerning rs7753873, a higher frequency of the
      AC genotype (p (c) = 0.015, OR [95% CI] 1.49 [1.17-1.91]) and C allele (p (c) =
      0.025, OR [95% CI] 1.39 [1.11-1.76]), and a lower frequency of the AA genotype (p
      (c) = 0.03, OR [95% CI] 0.68 [0.53-0.87]) and A allele (p (c) = 0.025, OR [95%
      CI] 0.72 [0.57-0.91]) were observed in BD patients. This study identified one
      strong risk SNP rs9494885 and two weak risk SNPs rs10499194 and rs7753873 of
      TNFAIP3 in Chinese Han BD patients.

PMID- 23161055
TI  - Arsenic trioxide toxicity in H9c2 myoblasts--damage to cell organelles and
      possible amelioration with Boerhavia diffusa.
AB  - Arsenic trioxide (ATO) has been long used as a chemotherapeutic agent because of
      its significant anticancer property. Unfortunately, the use of ATO is limited due
      to its cardiotoxic effects. The present study evaluates the protective property
      of ethanolic extract of Boerhavia diffusa (BDE) against ATO-induced toxicity on
      various cell organelles in H9c2 cardiomyocytes. The effects of different
      concentrations of ATO (5, 7.5 and 10 MUM) on cell organelles like mitochondria,
      endoplasmic reticulum (ER), lysosome and actin, generation of reactive oxygen
      species, antioxidant enzyme status and intracellular calcium overload were
      evaluated. ATO significantly (P <= 0.05) altered mitochondrial transmembrane
      potential, intracellular calcium level, ER, lysosomal activity and F-actin
      network in addition to induction of oxidative stress. Co-treatment with BDE
      protected the cardiomyocytes from the adverse effects of ATO, especially at 5 MUM
      concentration, which was evident from decreased activity of lactate dehydrogenase
      (5 MUM ATO + 20 MUg/mL BDE: 6.61 +/- 1.97 MUU/mL, respective control group: 16.15
      +/- 1.92 MUU/mL), reduced oxidative stress, calcium influx and organelle damage.
      Results obtained from the present study allow for a better characterization of
      the effects of ATO on H9c2 myoblasts. In conclusion, our data suggest that cell
      organelles are also the targets of ATO-induced cardiotoxicity in addition to
      other reported targets like ion channels, and BDE has the potential to protect
      the cardiotoxicity induced by ATO.

PMID- 23161056
TI  - Recent advances in enhancing the sensitivity of electrophoresis and
      electrochromatography in capillaries and microchips (2010-2012).
AB  - CE has been alive for over two decades now, yet its sensitivity is still regarded
      as being inferior to that of more traditional methods of separation such as HPLC.
      As such, it is unsurprising that overcoming this issue still generates much
      scientific interest. This review continues to update this series of reviews,
      first published in Electrophoresis in 2007, with updates published in 2009 and
      2011 and covers material published through to June 2012. It includes developments
      in the field of stacking, covering all methods from field amplified sample
      stacking and large volume sample stacking, through to isotachophoresis, dynamic
      pH junction and sweeping. Attention is also given to online or inline extraction
      methods that have been used for electrophoresis.

PMID- 23161057
TI  - Nine renal arteries in a Japanese female cadaver.
AB  - A rare case of multiple renal arteries was found in a 78-year-old female cadaver
      undergoing routine dissection. The characteristic findings in the cadaver
      included the presence of four right and four left renal arteries with one common
      trunk (a total of nine renal arteries). This variation may represent an immature
      form of complicated development of the renal arteries.

PMID- 23161058
TI  - Proteomic analysis of prion diseases: creating clarity or causing confusion?
AB  - Prion diseases, or transmissible spongiform encephalopathies, are progressive,
      fatal neurodegenerative diseases. There are both human and animal forms of the
      disease and all are associated with the conversion of a normal host-coded
      cellular prion protein (PrP(C) ) into an abnormal protease-resistant isoform
      (PrP(Sc) ). Although methodologies are sensitive and specific for postmortem
      disease diagnosis, the use of PrP(Sc) as a preclinical or general biomarker for
      surveillance is difficult, due to the fact that it is present in extremely small
      amounts in accessible tissues or body fluids such as blood, urine, saliva, and
      cerebrospinal fluid. Recently, amplification techniques have been developed,
      which have enabled increased sensitivity for PrP(Sc) detection. However, it has
      recently been reported that proteinase K sensitive, pathological isoforms of PrP
      may have a significant role in the pathogenesis of some prion diseases.
      Accordingly, the development of new diagnostic tests that do not rely on PrP(Sc)
      and proteinase K digestion is desirable. The search for biomarkers (other than
      PrP(Sc) ) as tools for diagnosis of prion diseases has a long history. Ideally
      biomarkers able to detect all transmissible spongiform encephalopathies, even at
      preclinical stages of infection are desirable but not yet possible due to the
      heterogeneity of the disease and lengthy disease progression. Recent advances in
      neuroproteomics have led to an overwhelming amount of information, which may
      offer insight on protein-protein interactions. While the amount of data obtained
      is impressive, the ability to relate it to the disease and validating its
      usefulness in diagnostic biomarker development remains a formidable challenge.

PMID- 23161059
TI  - Ectopic pregnancy: MRI findings and clinical utility.
AB  - PURPOSE: To assess the utility of magnetic resonance imaging (MRI) in patients
      with clinically suspected ectopic pregnancy (EP). METHODS: We retrospectively
      reviewed MRIs of 26 consecutive patients who were clinically suspected of having
      an EP. The diagnostic utility of MRI features of EP was analyzed retrospectively
      as follows: (1) Direct sign detection of ectopic gestational sac (GS); (2)
      Indirect signs tubal dilatation with hemosalpinx, adnexal hematoma, and
      hemorrhagic ascites. The diagnostic accuracy of each sign and their combination
      was compared to surgical records. The MRI findings of an ectopic GS were reviewed
      as follows: size, shape, signal intensity, and enhancement pattern. RESULTS: Of
      26 patients, 24 had a tubal pregnancy; 22 of these 24 patients (92%) had a direct
      sign (sensitivity: 91.3%; specificity: 100%; positive predictive value: 100%).
      The diagnostic accuracy of the direct sign was 92%; this was more accurate than
      that of any single indirect sign (39%, 54%, and 50%, respectively). However, the
      diagnostic accuracy of EP increased to 100% when diagnostic criteria required the
      presence of a direct sign or at least two indirect signs. CONCLUSIONS: MRI is an
      effective modality for diagnosing EP with a high detection rate of extrauterine
      GSs. The combination of direct and indirect signs is useful for establishing the
      correct diagnosis.

PMID- 23161061
TI  - Gene knockout and knockin by zinc-finger nucleases: current status and
      perspectives.
AB  - Zinc-finger nucleases (ZFNs) are engineered site-specific DNA cleavage enzymes
      that may be designed to recognize long target sites and thus cut DNA with high
      specificity. ZFNs mediate permanent and targeted genetic alteration via induction
      of a double-strand break at a specific genomic site. Compared to conventional
      homology-based gene targeting, ZFNs can increase the targeting rate by up to
      100,000-fold; gene disruption via mutagenic DNA repair is similarly efficient.
      The utility of ZFNs has been shown in many organisms, including insects,
      amphibians, plants, nematodes, and several mammals, including humans. This broad
      range of tractable species renders ZFNs a useful tool for improving the
      understanding of complex physiological systems, to produce transgenic animals,
      cell lines, and plants, and to treat human disease. 

PMID- 23161060
TI  - Co-ordinating Notch, BMP, and TGF-beta signaling during heart valve development.
AB  - Congenital heart defects affect approximately 1-5 % of human newborns each year,
      and of these cardiac defects 20-30 % are due to heart valve abnormalities. Recent
      literature indicates that the key factors and pathways that regulate valve
      development are also implicated in congenital heart defects and valve disease.
      Currently, there are limited options for treatment of valve disease, and
      therefore having a better understanding of valve development can contribute
      critical insight into congenital valve defects and disease. There are three major
      signaling pathways required for early specification and initiation of endothelial
      to-mesenchymal transformation (EMT) in the cardiac cushions: BMP, TGF-beta, and
      Notch signaling. BMPs secreted from the myocardium set up the environment for the
      overlying endocardium to become activated; Notch signaling initiates EMT; and
      both BMP and TGF-beta signaling synergize with Notch to promote the transition of
      endothelia to mesenchyme and the mesenchymal cell invasiveness. Together, these
      three essential signaling pathways help form the cardiac cushions and populate
      them with mesenchyme and, consequently, set off the cascade of events required to
      develop mature heart valves. Furthermore, integration and cross-talk between
      these pathways generate highly stratified and delicate valve leaflets and septa
      of the heart. Here, we discuss BMP, TGF-beta, and Notch signaling pathways during
      mouse cardiac cushion formation and how they together produce a coordinated EMT
      response in the developing mouse valves. 

PMID- 23161062
TI  - A kinesin-mediated mechanism that couples centrosomes to nuclei.
AB  - The M-type kinesin isoform, Kif9, has recently been implicated in maintaining a
      physical connection between the centrosome and nucleus in Dictyostelium
      discoideum. However, the mechanism by which Kif9 functions to link these two
      organelles remains obscure. Here we demonstrate that the Kif9 protein is
      localized to the nuclear envelope and is concentrated in the region underlying
      the centrosome point of attachment. Nuclear anchorage appears mediated through a
      specialized transmembrane domain located in the carboxyl terminus. Kif9 interacts
      with microtubules in in vitro binding assays and effects an endwise
      depolymerization of the polymer. These results suggest a model whereby Kif9 is
      anchored to the nucleus and generates a pulling force that reels the centrosome
      up against the nucleus. This is a novel activity for a kinesin motor, one
      important for progression of cells into mitosis and to ensure centrosome-nuclear
      parity in a multinuclear environment.

PMID- 23161064
TI  - Exploring in vivo violacein biosynthesis by application of multivariate curve
      resolution on fused UV-VIS absorption, fluorescence, and liquid chromatography
      mass spectrometry data.
AB  - In this work, the application of multivariate curve resolution-alternating least
      squares (MCR-ALS) is proposed for extracting information from multitechnique
      fused multivariate data (UV-VIS absorption, fluorescence, and liquid
      chromatography-mass spectrometry) gathered during the biosynthesis of violacein
      pigment. Experimental data sets were pretreated and arranged in a row-wise
      augmented data matrix before their chemometric investigation. Five different
      chemical components were resolved. Kinetic and spectral information about these
      components were obtained and their relationship with violacein biosynthesis was
      established. Three new chemical compounds with molar masses of 453, 465, and 479
      u, until now not reported in the literature, were identified and proposed as
      intermediates in the biosynthesis of other indolocarbazoles. The precursor
      (tryptophan), one intermediate (deoxyviolacein), and the final product
      (violacein) of violacein biosynthesis were identified and characterized using the
      proposed approach. The chemometric procedure based on the MCR-ALS method has
      proved to be a powerful tool to investigate violacein biosynthesis and its
      application can be easily extended to the study of other bioprocesses.

PMID- 23161066
TI  - Happy New Year--renewal, welcome, and farewell.

PMID- 23161065
TI  - Thin-layer chromatography enantioseparations on chiral stationary phases: a
      review.
AB  - The current state of chiral separations by thin-layer chromatography using chiral
      stationary phases is reviewed. Both stationary phases essentially constituted by
      the chiral selector and those obtained by the impregnation of achiral plates with
      appropriate chiral selectors are described. Particular attention is paid to
      commercial and non-commercial cellulose and cellulose-derivative plates, as well
      as commercially available ChiralplateTM, which are currently the most widely
      used. Some of the most important results obtained to date are reported and
      discussed; the examples provided illustrate the very wide range of structurally
      different solutes that can be readily resolved into their enantiomers by planar
      chromatographic methods. Special attention is paid to the discussion of the
      retention and resolution factors that influence chiral discrimination. The
      quantitative analysis of enantiomers is also discussed, especially from the point
      of view of determination of enantiomeric purity.

PMID- 23161063
TI  - Small molecule modifiers of circadian clocks.
AB  - Circadian clocks orchestrate 24-h oscillations of essential physiological and
      behavioral processes in response to daily environmental changes. These clocks are
      remarkably precise under constant conditions yet highly responsive to resetting
      signals. With the molecular composition of the core oscillator largely
      established, recent research has increasingly focused on clock-modifying
      mechanisms/molecules. In particular, small molecule modifiers, intrinsic or
      extrinsic, are emerging as powerful tools for understanding basic clock biology
      as well as developing putative therapeutic agents for clock-associated diseases.
      In this review, we will focus on synthetic compounds capable of modifying the
      period, phase, or amplitude of circadian clocks, with particular emphasis on the
      mammalian clock. We will discuss the potential of exploiting these small molecule
      modifiers in both basic and translational research. 

PMID- 23161067
TI  - Comparison of two different multidimensional liquid-gas chromatography interfaces
      for determination of mineral oil saturated hydrocarbons in foodstuffs.
AB  - This investigation focused on direct comparison of two popular multidimensional
      liquid-gas chromatography (LC-GC) systems, the Y-interface (retention gap
      approach) and the syringe-based interface (programmed temperature vaporizer
      approach). Such transfer devices are structurally very different, and could
      potentially have a substantial effect on the outcome of a specific application.
      In this work the application was a topic of much current interest, determination
      of mineral oil saturated hydrocarbon (MOSH) contamination of a series of food
      products (rice, pasta, icing sugar, olive oil); the final results were then
      compared. The two LC-GC methods developed were validated for linearity over the
      calibration range, analyte discrimination, precision, accuracy, and limits of
      detection and quantification. No significant differences were found between the
      two approaches.

PMID- 23161068
TI  - Fluorescence assay for protein post-translational tyrosine sulfation.
AB  - We developed a fluorescent assay to conveniently determine the kinetics of
      protein sulfation, which is essential for understanding interface between protein
      sulfation and protein-protein interactions. Tyrosylprotein sulfotransferase
      (TPST) catalyzes protein sulfation using 3'-phosphate 5'-phosphosulfate (PAPS) as
      sulfuryl group donor. In this report, PAPS was regenerated following sulfuryl
      group transfer between adenosine 3',5'-diphosphate and 4-methylumbelliferyl
      sulfate catalyzed by phenol sulfotransferase (PST). The TPST and PST coupled
      enzyme platform continuously generated fluorescent 4-methylumbelliferone (MU)
      that was used to real-time monitor protein sulfation. Using a recombinant N
      utilization substance protein A fused Drosophila melanogaster tyrosylprotein
      sulfotransferase, we demonstrated that the activity of TPST determined through MU
      fluorescence directly correlated with protein sulfation. Kinetic constants
      obtained with small P-selectin glycoprotein ligand-1 peptide (PSGL-1 peptide, MW
      1541) or its large glutathione S-transferase fusion protein (GST-PSGL-1, MW
      27833) exhibited significant variation. This assay can be further developed to a
      high-throughput method for the characterization of TPSTs and for the
      identification and screening of their protein substrates.

PMID- 23161070
TI  - Insulin resistance in patients undergoing peritoneal dialysis: can we improve it?
      : editorial to: "the effect of HM-CoA reductase inhibitor on insulin resistance
      in patients undergoing peritoneal dialysis" by Fa Mee Doh et al.

PMID- 23161071
TI  - A comprehensive analysis of the scientific scope of the papers.

PMID- 23161072
TI  - Prominin-1 (CD133): Molecular and Cellular Features Across Species.
AB  - Our knowledge of the first member of the prominin family is growing rapidly as
      the clinical value of prominin-1 (CD133) increases with its ever-wider use as a
      stem cell marker in normal and cancer tissues. Although the physiological
      function of this evolutionally conserved pentaspan membrane glycoprotein remains
      elusive, several studies have revealed new biological features regarding stem
      cells, cancer stem cells, and photoreceptors. The wide expression of CD133 in
      terminally differentiated epithelial cells, long overlooked by many authors, has
      attracted significant interest through the extensive investigation of human
      PROMININ-1 as a potential target for cancer therapies in various organs.
      Biochemically, this cholesterol-binding protein is selectively concentrated in
      plasma membrane protrusions, where it is associated with cholesterol-driven
      membrane microdomains. Clinically, mutations in the PROM1 gene are associated
      with various forms of retinal degeneration, which are mimicked in genetically
      modified mice carrying either a null allele or mutated form of PROMININ-1. In
      this introductory chapter, we attempted to review 15 years of prominin-1 study,
      focusing on its unique protein characteristics across species and the recent
      developments regarding its cell biology that may shed new light on its intriguing
      involvement in defining cancer-initiating cells.

PMID- 23161073
TI  - Prominin-2 and Other Relatives of CD133.
AB  - Several molecules related to prominin-1/CD133, which was first characterized as a
      marker of mouse neuroepithelial stem cells and human hematopoietic stem cells,
      have been identified in various species. In mammals, a second prominin gene,
      prominin-2, has been identified and characterized, whereas in nonmammalian
      species, up to three prominin genes are potentially expressed. The structural
      similarities between prominin-1 and prominin-2 are, to some extent, reflected by
      their biochemical properties; both proteins are selectively concentrated in
      specific plasma membrane subdomains that protrude into the extracellular space
      and are released in small extracellular membrane vesicles. In contrast to the
      apically confined prominin-1, prominin-2 is distributed in a nonpolarized apico
      basolateral fashion in polarized epithelial cells and appears to be expressed in
      separate epithelial cells. Their distinctive localization in plasma membrane
      protrusions is a hallmark of prominins, validating the naming of the family after
      its first identified member. Insights into the distinctive and/or complementary
      roles of the two prominins may be obtained by analyzing the evolutionary history
      of these proteins and the characteristics of orthologs and paralogs in more
      distantly related species. In addition, the characterization of prominins may
      shed light on the still elusive function of CD133.

PMID- 23161074
TI  - Prominin-1-containing membrane vesicles: origins, formation, and utility.
AB  - The stem cell antigen prominin-1 (CD133) is associated with two major types
      (small and large) of extracellular membrane vesicles in addition to its selective
      concentration in various kinds of plasma membrane protrusion. During development
      of the mammalian central nervous system, differentiating neuroepithelial stem
      cells release these vesicles into the embryonic cerebrospinal fluid. In
      glioblastoma patients, an increase of such vesicles, particularly the smaller
      ones, have been also observed in cerebrospinal fluid. Similarly, hematopoietic
      stem and progenitor cells release small ones concomitantly with their
      differentiation. Although the functional significance of these prominin-1
      containing membrane vesicles is poorly understood, a link between differentiation
      of stem (and cancer stem) cells and their release is emerging. In this chapter, I
      will summarize our knowledge about prominin-1-containing membrane vesicles
      including a potential role in cell-cell communication and highlight their
      prospective value as a new biomarker for tumorigenesis diagnostics.

PMID- 23161075
TI  - Prominent role of prominin in the retina.
AB  - Prominin molecules represent a new family of pentaspan membrane glycoproteins
      expressed throughout the animal kingdom. The name originates from its
      localization on membrane protrusion, such as microvilli, filopodia, lamellipodia,
      and microspikes. Following the original description in mouse and human,
      representative prominin members were found in fish (e.g., Danio rerio), amphibian
      (Ambystoma mexicanum, Xenopus laevis), worm (Caenorhabditis elegans), and flies
      (Drosophila melanogaster). Mammalian prominin-1 was identified as a marker of
      somatic and cancer stem cells and plays an essential role in the visual system,
      which contributed to increased interest of the medical field in this molecule.
      Here we summarize recent data from various fields, including Drosophila, which
      will aid to our understanding of its still elusive function.

PMID- 23161076
TI  - Gene Regulation of Prominin-1 (CD133) in Normal and Cancerous Tissues.
AB  - A pentaspan membrane glycoprotein prominin-1 (frequently called CD133 in human)
      is widely used as a surface marker to identify and isolate normal stem/progenitor
      cells from various organs, although it is also expressed in some types of
      differentiated cells. Since CD133 was identified as a universal marker to isolate
      cancer stem cells (CSCs) in tumors derived from multiple tissues, much attention
      has been directed toward the relationship between its gene regulation and
      identity of CSCs (i.e., cancer stemness). Prominin-1 (PROM1) gene possesses five
      alternative promoters yielding multiple first exons within the 5'-untranslated
      region (UTR) and also splicing variants affecting the open reading frame (ORF)
      sequence, implicating the complicated gene regulation in a context-dependent
      manner. This chapter aims to organize the accumulated findings on prominin-1 with
      a focus on its altered expression and regulation in normal and cancerous cells
      and to discuss potential regulatory networks underlying cancer stemness.

PMID- 23161077
TI  - Prominin-1 (CD133) and the Cell Biology of Neural Progenitors and Their Progeny.
AB  - Our group discovered prominin-1 in search for markers to study the cell polarity
      of neural stem and progenitor cells in the developing brain. Over the past 15
      years, prominin-1, also called CD133, has not only become a frequently used
      marker of neural stem cells and neural cancer stem cells, as is in fact the case
      of somatic (cancer) stem cells in general, but has also been used to understand
      the symmetric versus asymmetric division of the neural stem cells in the context
      of their apical-basal polarity. Moreover, studying prominin-1 on neural stem
      cells has revealed a novel fate of the midbody, that is, midbody release, and key
      differences in this release between normal stem cells and cancer-derived cells.
      Other subcellular aspects of neural stem cells, the understanding of which has
      been promoted by studying prominin-1, pertain to the organization of plasma
      membrane protrusions and the membrane microdomains they contain. Of particular
      relevance in this context is the primary cilium of neuroepithelial cells and its
      transformation into the outer segment of retinal photoreceptor cells, a process
      in which prominin-1 exerts a vital role.

PMID- 23161078
TI  - CD133-Positive Hematopoietic Stem Cells: From Biology to Medicine.
AB  - Lifelong hematopoiesis is sustained by a very small number of hematopoietic stem
      cells capable of self-renewal and differentiation into multiple hematopoietic
      lineages. The sialomucin CD34 has been, and is currently, used for the
      identification and purification of primitive hematopoietic progenitors. Depending
      on the source of stem cells, CD34 may not be expressed on all progenitor cells.
      An alternative stem cell marker is prominin-1 (CD133), which is expressed on a
      subpopulation of CD34(+) cells as well as on CD34(-) progenitor cells derived
      from various sources including fetal liver and bone marrow, adult bone marrow,
      cord blood, and mobilized peripheral blood. CD133(+) stem cells can reconstitute
      myelo- and lymphopoiesis of lethally irradiated mice, and the characterization of
      the CD133 expression on stem cells provides some insights into the biology of the
      hierarchy and functional organization of human hematopoiesis. The availability of
      methods for clinical large-scale isolation of CD133(+) cells facilitates their
      use in autologous and allogeneic hematopoietic stem cell transplantation and
      possibly in other fields of regenerative medicine.

PMID- 23161079
TI  - New Insights into the Renal Progenitor Cells and Kidney Diseases by Studying
      CD133.
AB  - CD133(+) progenitor cells have been found in different segments of the human
      nephron. In particular, CD133-expressing cells are present in the cortex, in
      Bowman's capsule of the glomerulus, and in proximal convoluted tubules and in
      medulla, in the Henle's loop, and its thin limb segments. The collecting ducts
      are negative. During repair of renal injury, CD133-expressing cells are
      increased, suggesting a contribution in renal regeneration. An increase has also
      been observed in pathological conditions. CD133(+) cells contribute to the
      formation of glomerular crescents and are lining the cysts in the polycystic
      kidney disease. Therefore, an altered regulation of CD133(+) cell proliferation
      or differentiation could be involved in glomerular and tubular response to injury
      in pathological condition. In clear cell renal carcinoma, despite CD133(+) cells
      appeared to contribute to tumor vascularization, they did not display features of
      tumor-initiating cells.

PMID- 23161081
TI  - New Insights into the CD133 (Prominin-1) Expression in Mouse and Human Colon
      Cancer Cells.
AB  - Following its discovery as a cancer stem cell marker, CD133 has been widely
      studied for its role in colorectal tumorigenesis. Indeed, colon cancer remains
      one of the major causes of cancer-related disease and death worldwide, and there
      is a strong need for an improvement of current diagnostic, prognostic, and
      therapeutic strategies. Thus, efforts have been devoted to try to understand
      whether CD133 might play a role in human colorectal tumorigenesis and might
      contribute to a better management of colon cancer patients. This chapter reviews
      the current knowledge on CD133 expression in normal and cancer colon tissues,
      both in humans and mice, discussing apparently conflicting data reported in the
      two species. Moreover, a great attention is devoted to the available information
      regarding the functional role of CD133 in colon cancer cells. Finally, the
      proposed clinical applications of CD133, as a prognostic and/or predictive marker
      as well as a target for novel antineoplastic strategies in colorectal cancer, are
      discussed. Overall, the available data support a potential important role of
      CD133 as cancer stem cell marker in colon cancer cells and warrant future studies
      to verify its potential use in the routine clinical management of colon cancer
      patients.

PMID- 23161080
TI  - CD133 Expression Strongly Correlates with the Phenotype of Very Small Embryonic
      /Epiblast-Like Stem Cells.
AB  - CD133 antigen (prominin-1) is a useful cell surface marker of very small
      embryonic-like stem cells (VSELs). Antibodies against it, conjugated to
      paramagnetic beads or fluorochromes, are thus powerful biological tools for their
      isolation from human umbilical cord blood, mobilized peripheral blood, and bone
      marrow. VSELs are described with the following characteristics: (1) are slightly
      smaller than red blood cells; (2) display a distinct morphology, typified by a
      high nuclear/cytoplasmic ratio and an unorganized euchromatin; (3) become
      mobilized during stress situations into peripheral blood; (4) are enriched in the
      CD133(+)Lin(-)CD45(-) cell fraction in humans; and (5) express markers of
      pluripotent stem cells (e.g., Oct-4, Nanog, and stage-specific embryonic antigen
      4). The most recent in vivo data from our and other laboratories demonstrated
      that human VSELs exhibit some characteristics of long-term repopulating
      hematopoietic stem cells and are at the top of the hierarchy in the mesenchymal
      lineage. However, still more labor is needed to characterize better at a
      molecular level these rare cells.

PMID- 23161082
TI  - Prominin-1 (CD133) Expression in the Prostate and Prostate Cancer: A Marker for
      Quiescent Stem Cells.
AB  - The origin and phenotype of stem cells in human prostate cancer remains a subject
      of much conjecture. In this scenario, CD133 has been successfully used as a stem
      cell marker in both normal prostate and prostate cancer. However, cancer stem
      cells have been identified without the use of this marker, opening up the
      possibility of a CD133 negative cancer stem cell. In this chapter, we review the
      current literature regarding prostate cancer stem cells, with specific reference
      to the expression of CD133 as a stem cell marker to identify and purify stem
      cells in normal prostate epithelium and prostate cancer.

PMID- 23161083
TI  - Prominin-1 (CD133) Reveals New Faces of Pancreatic Progenitor Cells and Cancer
      Stem Cells: Current Knowledge and Therapeutic Perspectives.
AB  - Islet transplantation-based therapies were proven successful for type 1 diabetes
      mellitus, but an extreme shortage of pancreatic islets has motivated recent
      efforts to develop renewable sources of islet-replacement tissue. Pancreatic
      progenitor cells hold a promising potential, yet attempts at their prospective
      isolation are scarce due to the lack of specific marker. We found that prominin-1
      (often referred to as CD133 in humans) is expressed by the undifferentiated
      epithelial cells in the mouse embryonic pancreas. Putative pancreatic epithelial
      stem and progenitor cells were prospectively enriched in prominin-1(+) cell
      population by cell sorting and characterized. CD133 is also a cell surface marker
      of human pancreatic cancer stem cells (CSC), which are resistant to conventional
      treatments such as chemotherapy and radiotherapy. Therefore, a considerable
      interest in the specific targeting and eradication of CSC is emerging for the
      cancer therapy, and CD133 may represent a good molecular target. In this chapter,
      I will summarize our current knowledge about prominin-1/CD133 in mouse and human
      pancreas.

PMID- 23161084
TI  - Prominin-1 (CD133) and Metastatic Melanoma: Current Knowledge and Therapeutic
      Perspectives.
AB  - Innovative approaches to specifically target the melanoma subpopulation
      responsible for local invasion and metastatic dissemination are needed. Prominin
      1 (CD133) expression has been observed in many melanoma cell lines, as well as in
      primary and metastatic melanomas from patients. Although its function(s) in
      melanoma is presently unknown, prominin-1 may represent a molecular target, due
      to its association with melanoma stem cells and with the metastatic phenotype.

PMID- 23161085
TI  - CD133-Positive Cells for Cardiac Stem Cell Therapy: Current Status and Outlook.
AB  - Ischemic heart disease represents one major cause of death in developed
      countries. Ten years ago, cardiac application of bone marrow-derived progenitor
      cells was introduced as a new therapeutic strategy with the aim of restoring the
      function of ischemic myocardium. Among other cell populations, CD133(+) bone
      marrow stem cells form a major subpopulation of progenitor cells studied in this
      context. Following promising preclinical evidence, both cardiac surgeons and
      interventional cardiologists have applied CD133(+) cells in setting of chronic
      ischemic heart failure as well as acute myocardial infarction within phase I and
      II clinical trials. This chapter summarizes the rationale for the use of this
      stem cell subpopulation in the field of regenerative cardiac therapy strategies
      and gives an overview on the current clinical evidence as well as upcoming phase
      III trials.

PMID- 23161086
TI  - CD133(+) Cells for the Treatment of Degenerative Diseases: Update and
      Perspectives.
AB  - Stem cells are used in cell therapy for degenerative disorders. The main
      advantage of stem cells is that they can replenish their numbers for long periods
      through cell division and produce a progeny that can differentiate into multiple
      cell lineages with specific functions. CD133 is a member of a novel family of
      cell surface glycoproteins. The expression of human CD133 (AC133 antigen) was
      originally described in the hematopoietic CD34(+) stem cells, but now it becomes
      more and more evident that CD133 is a marker of stem and progenitor cell
      populations originating from various tissues and organs. The main objective of
      this chapter is to describe the potential sources of CD133(+) stem cells that
      harbor the ability to engraft, proliferate, and differentiate into functional
      cells. The characterization of such CD133(+) stem cells unlocks new opportunities
      in the treatment of degenerative diseases such as Duchenne muscular dystrophy.

PMID- 23161087
TI  - The expression pattern of classical MHC class I molecules in the development of
      mouse central nervous system.
AB  - Classical major histocompatibility complex (MHC) class I, first identified in the
      immune system, is also expressed in the developing and adult central nervous
      system (CNS). Although the MHC class I molecules have been found to be expressed
      in the CNS of different species, a necessary step to elucidate the temporal and
      spatial expression patterns of MHC class I molecules in the brain development has
      never been taken. Frozen sections were made from the brains of embryonic and
      postnatal C57BL/6 J mice, and the expression of H-2D(b) mRNA was examined by in
      situ hybridization. Immunofluorescence was also performed to define the cell
      types that express H2-D(b) in P15 mice. At E10.5, the earliest stage we examined,
      H2-D(b) was expressed in neuroepithelium of the brain vesicles. From E12.5 to P0,
      H2-D(b) expression was mainly located at cerebral cortex, neuroepithelium of the
      lateral ventricle, neuroepithelium of aquaeductus and developing cerebellum. From
      P4 to adult, H2-D(b) mRNA was detected at olfactory bulb, hippocampus, cerebellum
      and some nerve nuclei. The major cell types expressing H-2D(b) in P15
      hippocampus, cerebral cortex and olfactory bulb were neuron. H2-K(b) signal
      paralleled that of H2-D(b) and the expression levels of the two molecules were
      comparable throughout the brain. The investigation of the expression pattern of H
      2D(b) at both embryonic and postnatal stages is important for further
      understanding the physiological and pathological roles of H2-D(b) in the
      developing CNS.

PMID- 23161088
TI  - Bovine brain myelin glycerophosphocholine choline phosphodiesterase is an
      alkaline lysosphingomyelinase of the eNPP-family, regulated by lysosomal sorting.
AB  - Glycerophosphocholine choline phosphodiesterase (GPC-Cpde) is a
      glycosylphosphatidylinositol (GPI)-anchored alkaline hydrolase that is expressed
      in the brain and kidney. In brain the hydrolase is synthesized by the
      oligodendrocytes and expressed on the myelin membrane. There are two forms of
      brain GPC-Cpde, a membrane-linked (mGPC-Cpde) and a soluble (sGPC-Cpde). Here we
      report the characterisation sGPC-Cpde from bovine brain. The amino acid sequence
      was identical to ectonucleotide pyrophosphatase/phosphodiesterase 6 (eNPP6)
      precursor, lacking the N-terminal signal peptide region and a C-terminal stretch,
      suggesting that the hydrolase was solubilised by C-terminal proteolysis,
      releasing the GPI-anchor. sGPC-Cpde existed as two isoforms, a homodimer joined
      by a disulfide bridge linking C414 from each monomer, and a monomer resulting
      from proteolysis N-terminally to this disulfide bond. The only internal disulfide
      bridge, linking C142 and C154, stabilises the choline-binding pocket. sGPC-Cpde
      was specific for lysosphingomyelin, displaying 1 to 2 orders of magnitude higher
      catalytic activity than towards GPC and lysophosphatidylcholine, suggesting that
      GPC-Cpde may function in the sphingomyelin signaling, rather than in the
      homeostasis of acylglycerophosphocholine metabolites. The truncated high mannose
      and bisected hybrid type glycans linked to N118 and N341 of sGPC-Cpde is a
      hallmark of glycans in lysosomal glycoproteins, subjected to GlcNAc-1
      phosphorylation en route through Golgi. Thus, sGPC-Cpde may originate from the
      lysosomes, suggesting that lysosomal sorting contributes to the level of mGPC
      Cpde on the myelin membrane.

PMID- 23161089
TI  - HSPA5 forms specific complexes with copper.
AB  - Our previous study indicated that Hspa5 directly interacts with copper (Cu) to
      maintain Cu homeostasis in astrocytes. In this study, we explored the possibility
      that Cu forms a specific complex with Hspa5 by assaying stoichiometric binding of
      Cu and other metals to recombinant human HSPA5 (rh-HSPA5) in silico.
      Spectrophotometric analysis showed that incubation of rh-HSPA5 with Cu but not
      with Fe, Mn, Zn, or Pb in the presence of ascorbic acid produced an absorbance
      peak at 470 nm. Furthermore, the absorbance peak was absent when bovine serum
      albumin was incubated with Cu and when another recombinant protein YWHAZ-14-3-3
      Zeta carrying a 6* histidine tag identical to the tag in the rh-HSPA5 was
      incubated with Cu. The absorbance peak produced by Cu and rh-HSPA5 was abolished
      by EDTA treatment and was stabilized at pH levels above 6.5. Assay of the
      stoichiometry of metal binding to the purified rh-HSPA5 showed that one molecule
      of the rh-HSPA5 could chelate 1 or 2 Cu, 13 iron (Fe), 5 zinc (Zn) and 10 lead
      (Pb) ions but not manganese (Mn). These data further support our previous finding
      that HSPA5 specifically forms a complex with Cu to help maintain Cu homeostasis.

PMID- 23161090
TI  - Neuroprotective efficacy of eugenol and isoeugenol in acrylamide-induced
      neuropathy in rats: behavioral and biochemical evidence.
AB  - The primary objective of this investigation was to assess the neuroprotective
      efficacy of spice active principles namely Eugenol (Eug) and isoeugenol (IE) in
      an acrylamide (ACR) neuropathy model in rats. In the present study, ACR
      administration (50 mg/kg bw, i.p. 3 times/week) for 5 weeks to growing rats
      caused typical symptoms of neuropathy. We found that treatment of ACR rats with
      spice active principles (10 mg/kg bw, for 5 weeks) caused marked improvement in
      gait score and responses in a battery of behavioral tests. Terminally, both spice
      active principles markedly attenuated ACR-induced markers of oxidative stress
      viz., reactive oxygen species (ROS), malondialdehyde (MDA) and nitric oxide (NO)
      in sciatic nerve (SN) as well as brain regions (cortex Ct, cerebellum Cb).
      Treatment with Eug restored the reduced glutathione levels in SN and brain
      regions. Interestingly, both spice active principles effectively diminished ACR
      induced elevation in cytosolic calcium levels and acetylcholinesterase activity
      in SN and Ct. Further, the diminished activity of ATPase among ACR rats was
      enhanced in SN and restored in brain regions. Furthermore, Eug treatment
      significantly offset ACR-induced depletion in dopamine levels in brain regions.
      Collectively our findings suggest the propensity of these spice active principles
      to attenuate ACR-induced neuropathy. Further studies are necessary to understand
      the precise molecular mechanism/s by which these spice active principles
      attenuate neuropathy. Nevertheless, our data clearly demonstrate the beneficial
      effects of spice active principles in ACR-induced neuropathy in rats and suggest
      their possible therapeutic usage as an adjuvant in the management of other forms
      of neuropathy in humans.

PMID- 23161091
TI  - Diabetes and intermediate hyperglycaemia in Kisantu, DR Congo: a cross-sectional
      prevalence study.
AB  - OBJECTIVES: To study the prevalence and risk markers of diabetes mellitus and
      intermediate hyperglycaemia (IH) in Kisantu, a semirural town in Bas-Congo
      province, The Democratic Republic of Congo. DESIGN: A cross-sectional population
      based survey. SETTINGS: A modified WHO STEPwise strategy was used. Capillary
      glycaemia was measured for fasting plasma glucose and 2-h-postload glucose. Both
      WHO/IDF (International Diabetes Federation) 2006 and American Diabetes
      Association (ADA) 2003 diagnostic criteria for diabetes and IH were used.
      PARTICIPANTS: 1898 subjects aged >= 20 years. RESULTS: Response rate was 93.7%.
      Complete data were available for 1759 subjects (86.9%). Crude and standardised
      (for Doll and UN population) prevalence of diabetes were 4.8% and 4.0-4.2%. Crude
      IH prevalence was 5.8% (WHO/IDF) and 14.2% (ADA). Independent risk markers for
      diabetes (p<0.01) were male (OR 2.5), age 50-69 years (OR 2.6), family history
      (OR 3.5), waist (OR 4.1) and alcohol consumption (OR 0.36). In receiver operating
      characteristic (ROC) analysis, prediction of diabetes was slightly better by
      waist than body mass index (BMI). IH defined according to WHO/IDF was associated
      with BMI (OR 2.6, p<0.001). IH defined according to ADA was associated (p<0.05)
      with waist (OR 1.4), education level (OR 1.6), BMI (OR 2.4) and physical activity
      (OR 0.7). CONCLUSIONS: Current prevalence of diabetes in DR Congo exceeds IDF
      projections for 2030. The lower glucose threshold used by ADA almost triples
      impaired fasting glucose prevalence compared to WHO/IDF criteria. The high
      proportion of disorders of glycaemia made up by IH suggests the early stages of a
      diabetes epidemic.

PMID- 23161092
TI  - Promoting physical activity in sedentary elderly Malays with type 2 diabetes: a
      protocol for randomised controlled trial.
AB  - INTRODUCTION: Like many countries Malaysia is facing an increase in the number of
      people with type 2 diabetes mellitus diabetes (T2DM) and modifiable lifestyle
      factors such as sedentary behaviour are important drivers of this increase. The
      level of physical activity is low among elderly Malay people. In Malaysia,
      strategies to promote physical activity in elderly Malay people with T2DM are not
      well documented in the research literature. This paper discusses an intervention
      to increase physical activity in elderly Malay people with T2DM. The aim of our
      study was to evaluate the effectiveness of personalised feedback alone and in
      combination with peer support in promoting and maintaining physical activity in
      comparison with usual care. METHODS AND ANALYSIS: A three-arm randomised
      controlled trial will be conducted among sedentary Malay adults aged 60 years and
      above with T2DM attending an urban primary healthcare clinic in Malaysia. The
      participants will be randomised into three groups for a 12-week intervention with
      a follow-up at 24 and 36 weeks to assess adherence. The primary outcome of this
      study is pedometer-determined physical activity. Glycaemic and blood pressure
      control, body composition, cardiorespiratory fitness, balance, lipid profile,
      health-related quality of life, psychological well-being, social support and self
      efficacy for exercise are the secondary measures. Linear mixed models will be
      used to determine the effect of the intervention over time and between groups.  
      ETHICAL AND DISSEMINATION:  The Monash University Human Research Ethics Committee
      and the Malaysian Ministry of Health's Medical Research Ethics Committee approved
      this protocol. The findings of this study will be presented at international
      conferences and published in peer-reviewed journals. TRIAL REGISTRATION: This
      study protocol has been registered with the Malaysian National Medical Research
      Registry and with the Current Controlled Trial Ltd (http://www.controlled
      trials.com/ISRCTN71447000/).

PMID- 23161093
TI  - Research on a vulnerable neighborhood-the vancouver downtown eastside from 2001
      to 2011.
AB  - The Downtown Eastside (DTES) of Vancouver is the subject of considerable research
      due to high rates of drug use, poverty, crime, infectious disease, and mental
      illness. This paper first presents a brief background to the DTES and then
      presents a survey of literature addressing the issues in this area from 2001 to
      2011. The literature surveyed includes a range of publications such as those from
      peer-reviewed journals and the grey literature of reports and dissertations. This
      survey investigates the themes and outcomes of the extant literature and
      highlights the notable lack of research on mental health in the DTES.

PMID- 23161095
TI  - HIV-1 drug resistance-associated mutations among antiretroviral-naive Thai
      patients with chronic HIV-1 infection.
AB  - Antiretroviral therapy (ART) has increased in resource-limited settings. This
      study determined the prevalence of HIV-1 drug resistance-associated mutations
      (DRAMs) among patients with chronic HIV-1 infections and compare DRAMs between
      CRF01_AE and B subtypes. ART-naive Thai patients who had ART initiation between
      2010 and 2011 were enrolled prospectively. Genotypic assays were performed on
      viral reverse transcriptase and protease genes within 4 weeks before starting
      ART. DRAMs were assessed using the International AIDS Society-USA 2011 list. A
      total of 330 patients were included. HIV-1 subtypes included CRF01_AE (73%), B
      (23.9%), and others (3.1%). Median (IQR) CD4+ was 66 (23-172) cells/mm(3) and
      median (IQR) HIV-1 RNA was 5.2 (4.6-5.8) log copies/ml. The prevalence of
      patients with >=1 DRAMs for any antiretroviral agents was 17.6%. DRAM prevalence
      was 17% for non-nucleoside reverse transcriptase inhibitors (NNRTIs), 0.6% for
      NRTIs, and 0.6% for protease inhibitors (PIs). DRAMs to NNRTIs were V106I (7%),
      V179D (4.2%), V179T (1.8%), E138A (1.5%), V90I (1.2%), K103N (0.9%), Y181C
      (0.9%), and P225H (0.3%). DRAMs to NRTIs were M184V (0.3%) and T215S (0.3%). The
      only major DRAM for PIs was M46L (0.6%). Minor DRAMs to PIs including I13V, M36I,
      H69K, and L89M were observed more frequently in CRF_01 AE. By multivariate
      analysis, the factors "HIV-1 subtype B" and "low pretreated CD4+ cell count" were
      associated with a higher rate of DRAMs. HIV-1 DRAMs, especially to NNRTIs, are
      emerging in a middle-income country after widespread use of NNRTI-based ART. HIV
      genotypic assays before ART initiation in patients with chronic HIV-1 infection
      should be considered.

PMID- 23161097
TI  - 3D numerical simulation of a Coulter counter array with analysis of
      electrokinetic forces.
AB  - Coulter counters have played an important role in biological cell assays since
      their introduction decades ago. Several types of high throughput micro-Coulter
      counters based on lab-on-chip devices have been commercialized recently. In this
      paper, we propose a highly integrated micro-Coulter counter array working under
      low DC voltage. The real-time electrical current change, including the pulse
      amplitude and width, of the micro-Coulter counter with novel structure is
      systematically investigated numerically. The major types of forces exerted on the
      particle in the micro-Coulter counter, including hydrodynamic force and
      electrokinetic force are quantitatively analyzed. The simulation in this study
      shows the pulse profile, such as width and amplitude, is affected by both
      particle size and the flow condition. The special cases of multiple particle
      aggregation and cross-talk between neighboring channels are also considered for
      their effects on the electric current pulses. This simulation provides critical
      insight and guidance for developing next new generations of micro-Coulter
      counter.

PMID- 23161096
TI  - LIN28A immunoreactivity is a potent diagnostic marker of embryonal tumor with
      multilayered rosettes (ETMR).
AB  - Embryonal tumor with multilayered rosettes (ETMR, previously known as ETANTR) is
      a highly aggressive embryonal CNS tumor, which almost exclusively affects infants
      and is associated with a dismal prognosis. Accurate diagnosis is of critical
      clinical importance because of its poor response to current treatment protocols
      and its distinct biology. Amplification of the miRNA cluster at 19q13.42 has been
      identified previously as a genetic hallmark for ETMR, but an immunohistochemistry
      based assay for clinical routine diagnostics [such as INI-1 for atypical teratoid
      rhabdoid tumor (AT/RT)] is still lacking. In this study, we screened for an ETMR
      specific marker using a gene-expression profiling dataset of more than 1,400
      brain tumors and identified LIN28A as a highly specific marker for ETMR. The
      encoded protein binds small RNA and has been implicated in stem cell
      pluripotency, metabolism and tumorigenesis. Using an LIN28A specific antibody, we
      carried out immunohistochemical analysis of LIN28A in more than 800 childhood
      brain-tumor samples and confirmed its high specificity for ETMR. Strong LIN28A
      immunoexpression was found in all 37 ETMR samples tested, whereas focal
      reactivity was only present in a small (6/50) proportion of AT/RT samples. All
      other pediatric brain tumors were completely LIN28A-negative. In summary, we
      established LIN28A immunohistochemistry as a highly sensitive and specific,
      rapid, inexpensive diagnostic tool for routine pathological verification of ETMR.

PMID- 23161098
TI  - Orexin-B-like immunoreactivity localizes in both luteinizing-hormone-containing
      cells and melanin-concentrating hormone-containing fibers in the red-bellied
      piranha (Pygocentrus nattereri) pituitary.
AB  - We examined orexin-like immunoreactivity in the pituitary of the red-bellied
      piranha (Pygocentrus nattereri). Orexin-B-immunoreactive (IR) cells corresponded
      to luteinizing hormone (LH)-containing cells in the pars distalis, and orexin-B
      IR fibers corresponded to melanin-concentrating hormone (MCH)-containing fibers
      in the pars nervosa. In the pars distalis, orexin-B-IR puncta that were also
      immunoreactive for MCH were observed around the orexin-B-IR cells. In the ventral
      hypothalamus, orexin-B-IR and MCH-IR neurons were found in the nucleus lateralis
      tuberis. Immunoelectron-microscopic analysis revealed that the orexin-B-like
      substance co-localized with LH in secretory granules and with MCH in MCH
      containing neurons. Some of the MCH secreted in the pituitary might participate
      in the modulation of LH secretion from the gonadotrophs, together with orexin-B,
      leading to food intake by the stimulation of growth hormone secretion from the
      somatotrophs.

PMID- 23161099
TI  - Activation of autophagic programmed cell death and innate immune gene expression
      reveals immuno-competence of integumental epithelium in Bombyx mori infected by a
      dipteran parasitoid.
AB  - In insects, the integument forms the primary barrier between the environment and
      internal milieu, but cellular and immune responses of the integumental epithelium
      to infection by micro- and macro-parasites are mostly unknown. We elucidated
      cellular and immune responses of the epithelium induced through infection by a
      dipteran endoparasitoid, Exorista bombycis in the economically important silkworm
      Bombyx mori. Degradative autophagic vacuoles, lamella-like bodies, a network of
      cytoplasmic channels with cellular cargo, and an RER network that opened to
      vacuoles were observed sequentially with increase in age after infection. This
      temporal sequence culminated in apoptosis, accompanied by the upregulation of the
      caspase gene and fragmentation of DNA. The infection significantly enhanced the
      tyrosine level and phenol oxidase activity in the integument. Proteomic analysis
      revealed enhanced expression of innate immunity components of toll and
      melanization pathways, cytokines, signaling molecules, chaperones, and
      proteolytic enzymes demonstrating diverse host responses. qPCR analysis revealed
      the upregulation of spatzle, BmToll, and NF kappa B transcription factors Dorsal
      and BmRel. NF kappa B inhibitor cactus showed diminished expression when Dorsal
      and BmRel were upregulated, revealing a negative correlation (R = (-)0.612).
      During melanization, prophenol oxidase 2 was expressed, a novel finding in
      integumental epithelium. The integument showed a low level of melanin metabolism
      and localized melanism in order to prevent the spreading of cytotoxic quinones.
      The gene-encoding proteolytic enzyme, beta-N-acetylglucosaminidase, was activated
      at 24 h post-infection, whereas chitinase, was activated at 96 h post-infection;
      however, most of the immune genes enhanced their expression in the early stages
      of infection. Thus the integument contributes to humoral immune responses that
      enhance resistance against macroparasite invasion.

PMID- 23161100
TI  - Case report: Rhabdomyolysis in morbidly obese patients: anesthetic
      considerations.
AB  - PURPOSE: We report the presentation and management of rhabdomyolysis involving
      shoulder girdle and upper arm muscles in a morbidly obese patient after prolonged
      laparoscopic surgery. CLINICAL FEATURES: A 41-yr-old morbidly obese woman
      presented for laparoscopic abdominal hysterectomy. She had hypertension and type
      II diabetes which were controlled on regular medications. She also had
      obstructive sleep apnea. Her clinical examination and investigations revealed no
      abnormality except morbid obesity (body mass index 54 kg.m(-2)) and left
      ventricular hypertrophy on transthoracic echocardiogram. Standard general
      anesthesia was administered under baseline non-invasive monitors. Succinylcholine
      was used to secure the airway during anesthetic induction. Surgery was performed
      with the patient positioned with a 15 degrees  head-down tilt, and it took six
      hours to complete the procedure as technical difficulty was encountered due to
      her body habitus. Her trachea was extubated and she was transferred to the
      postanesthetic care unit (PACU) without incident. In the PACU, the patient
      complained of severe bilateral arm pain and weakness an hour after surgery. On
      physical examination, she exhibited limited movement of her arms against gravity
      while complaining of tenderness in her shoulder girdle muscles and both arms.
      Clinical suspicion of rhabdomyolysis based on her signs and symptoms was
      confirmed by an elevated serum creatinine kinase (CK) of 18,392 IU.L(-1) and
      serum potassium of 5.3 mmol.L(-1). Intravenous crystalloids and mannitol were
      administered for 24 hr for renal protection, and her clinical symptoms and serum
      CK levels improved over seven days. The patient was discharged to home on the
      tenth postoperative day, and she continued to improve over the three-month follow
      up period. CONCLUSIONS: Morbidly obese patients who undergo prolonged surgery are
      at risk for rhabdomyolysis, and early diagnosis and therapy are required to
      prevent severe complications.

PMID- 23161101
TI  - Simultaneous determination of acidic and basic drugs using dual hollow fibre
      electromembrane extraction combined with CE.
AB  - The simultaneous extraction of acidic and basic drugs from biological samples is
      a significant challenge for sample preparation. A novel and efficient method
      named dual hollow fibre electromembrane extraction combined with CE was applied
      for the simultaneous extraction and preconcentration of acidic and basic drugs in
      a single step. Under applied potential of 40 V during the extraction, ibuprofen
      as an acidic drug and thebaine as a basic drug migrated from a 4 mL aqueous
      sample solution at neutral pH into 20 MUL of each basic (pH 12.5) and acidic (pH
      2.0) acceptor phase, respectively; 1-octanol and 2-nitrophenyl octyl ether were
      immobilised in the pores of anodic and cathodic hollow fibres as supported liquid
      membranes, respectively. A Box-Behnken design and the response surface
      methodology were used for the optimisation of different parameters on the
      extraction efficiency. Under the optimised conditions, the enrichment factors
      were between 150 and 170 and also the LODs ranged from 3 to 7 ng/mL in different
      samples. The method was reproducible so that intra- and inter-day RSDs% (n = 5)
      were less than 5.9%. Finally, the method was successfully applied for the
      simultaneous extraction and determination of acidic and basic drugs from plasma
      and urine samples.

PMID- 23161102
TI  - Non-native states of bovine beta-lactoglobulin induced by acetonitrile: pH
      dependent unfolding of the two genetic variants A and B.
AB  - Acetonitrile (ACN)-induced unfolding of the beta-lactoglobulin variants A and B
      was investigated at pH 2.0, 7.0 and 9.0. ACN caused alpha-helix induction at low
      concentrations but lead to major conformational alterations when the
      concentration was raised. ACN also induced a concentration-dependent increase in
      the surface hydrophobicity of both the variants. Induction of alpha-helical
      structure and exposure of hydrophobic patches were, however, somewhat more
      pronounced in case of variant B, whereas the loss of tertiary structure was more
      marked for variant A. Both protein aggregation and helix induction necessitated
      higher ACN concentrations at pH 2.0 than at 7.0 and 9.0, suggesting the greater
      stability of the variants at acidic pH.

PMID- 23161103
TI  - Gossypol interferes with both type I and type II topoisomerase activities without
      generating strand breaks.
AB  - A considerable number of agents with chemotherapeutic potentials reported over
      the past years were shown to interfere with the reactions of DNA topoisomerases,
      the essential enzymes that regulate conformational changes in DNA topology.
      Gossypol, a naturally occurring bioactive phytochemical is a chemopreventive
      agent against various types of cancer cell growth with a reported activity on
      mammalian topoisomerase II. The compounds targeting topoisomerases vary in their
      mode of action; class I compounds act by stabilizing covalent topoisomerase-DNA
      complexes resulting in DNA strand breaks while class II compounds interfere with
      the catalytic function of topoisomerases without generating strand breaks. In
      this study, we report Gossypol as the interfering agent with type I
      topoisomerases as well. We also carried out an extensive set of assays to analyze
      the type of interference manifested by Gossypol on DNA topoisomerases. Our
      results strongly suggest that Gossypol is a potential class II inhibitor as it
      blocked DNA topoisomerase reactions with no consequently formed strand breaks.

PMID- 23161104
TI  - High levels of glucose induced the caspase-3/PARP signaling pathway, leading to
      apoptosis in human periodontal ligament fibroblasts.
AB  - Periodontitis is one of the main complications of diabetes mellitus, and much
      research has been conducted on their relationship. However, the mechanism by
      which high glucose levels induce damage of periodontal ligament fibroblasts is
      still unclear. In this study, we investigated the effects of high glucose levels
      on apoptosis in human periodontal ligament fibroblasts and the possible
      mechanisms involved. Human periodontal ligament fibroblasts were cultured in DMEM
      with normal glucose (5.5 mM) and high glucose (35 mM) levels for 6, 12, or 24 h.
      Apoptosis was studied by flow cytometry, caspase assays, fluorescent real-time
      PCR, and Western-blot analysis. The different durations of high glucose
      incubation induced a time-dependent increase of apoptosis and caspase-3 activity
      in cultured human periodontal ligament fibroblasts. In addition, concentrations
      of caspase-3 and its substrate PARP in cultured human periodontal ligament
      fibroblasts increased in a time-dependent manner. Furthermore, a caspase-3
      inhibitor could prevent the high glucose-induced apoptosis in human periodontal
      ligament fibroblasts. These data indicate that high glucose induces a time- and
      caspase-3-dependent increase in apoptosis in cultured human periodontal ligament
      fibroblasts. These results elucidate the mechanism for the regulation of human
      periodontal ligament fibroblast apoptosis caused by high glucose.

PMID- 23161105
TI  - A new insight into structural and functional impact of single-nucleotide
      polymorphisms in PTEN gene.
AB  - Phosphatase and tensin homolog (PTEN) plays essential roles in cellular processes
      including survival, proliferation, energy metabolism, and cellular architecture.
      Activating the mutations of PTEN has long been known to produce a variety of
      disorders, mainly diabetes and cancer in humans. Owing to the importance of PTEN
      gene, a functional analysis using different in silico approaches was undertaken
      to explore the possible associations between genetic mutations and phenotypic
      variation. SIFT, PolyPhen, I-Mutant 3.0, SNP&GO, and PHD-SNP were used for
      initial screening of functional nsSNPs. From the observed results, three
      mutations R47G, H61D, and V343E were selected based on their surface
      accessibility and total energy change. By molecular dynamics approach, H61D
      showed increase in flexibility, radius of gyration, solvent accessibility, and
      deviated more from the native structure which was supported by the decrease in
      the number of hydrogen bonds. Further from principal component analysis and
      interaction analysis, we identified significant structural changes that can
      reasonably explain the involvement of deviations in stability caused by
      mutations. Our analysis also predicts the involvement of SNPs that could
      potentially influence post-translational modifications in PTEN gene. These in
      silico predictions could provide a new insight into structural and functional
      impact of PTEN polymorphisms.

PMID- 23161106
TI  - CE-MS for metabolomics: developments and applications in the period 2010-2012.
AB  - CE-MS has emerged as a powerful technique for the profiling of (highly) polar and
      charged metabolites in biological samples. This review provides an update of the
      most recent developments in CE-MS for metabolomics covering the scientific
      literature from July 2010 to June 2012. The present paper is an update of two
      previous review papers covering the years 2000-2010 (Electrophoresis 2009, 30,
      276-291; Electrophoresis 2011, 32, 52-65). Emerging technological developments
      used in CE-MS for metabolomics are discussed, such as the use of novel
      interfacing techniques for coupling CE to MS. Representative examples illustrate
      the applicability of CE-MS in the fields of biomedical, clinical, microbial,
      plant, environmental and food metabolomics. Concerning targeted and non-targeted
      approaches, a comprehensive overview of recent CE-MS-based metabolomics studies
      is given in a table. Information on sample type and pretreatment, capillary
      coatings and MS detection mode is provided. Finally, general conclusions and
      perspectives are provided.

PMID- 23161107
TI  - Elucidation of the binding properties of a photosensitizer to salmon sperm DNA
      and its photobleaching processes by spectroscopic methods.
AB  - Methylene blue (MB) is a tricyclic heteroaromatic photosensitizer with a
      promising application in the photodynamic therapy (PDT) for anticancer treatment.
      The binding properties of MB to salmon sperm DNA have been investigated by the
      measurements of absorption spectra, quenching experiments and the photobleaching
      processes. Remarkable hypochromic and bathochromic effects of MB in the presence
      of increasing amounts of DNA have been observed in the absorption spectra. The
      quenching of MB by the DNA bases obeys the Stern-Volmer equation and ferrocyanide
      quenching of MB in the absence and presence of DNA is also measured as extended
      experiments. Results from the above spectral measurements are all consistent with
      the intercalative binding mode of MB to DNA with the K b value of 5.6 * 10(3) M(
      1). The photobleaching processes of MB and its DNA complex have also been
      studied, which indicate that the photobleaching of MB and its DNA complex proceed
      with different mechanisms and the reactive oxygen species are responsible for the
      self-sensitized photooxidation of MB.

PMID- 23161108
TI  - Cartilage repair of the knee with Hyalograft C:(r) magnetic resonance imaging
      assessment of the glycosaminoglycan content at midterm.
AB  - PURPOSE: The aim of this study was to assess the stability of the
      glycosaminoglycan (GAG) content in the long term after matrix-associated
      autologous chondrocyte transplantation (MACT) with Hyalograft C in the knee over
      a follow-up period of one year. METHODS: In this cross-sectional evaluation, 11
      patients after MACT of the knee consented to delayed gadolinium-enhanced magnetic
      resonance imaging of cartilage (dGEMRIC) measurements. The mean post-operative
      interval before the first MR examination was 40.6 +/- 22.0 months, and the second
      MR examination was carried out after another 12 months. The Lysholm score was
      assessed for clinical evaluation. Quantitative T1 measurements after intravenous
      negatively charged MR contrast agent administration were performed. Global post
      contrast T1 of the reference cartilage and the repair tissue and a relative post
      contrast T1 value were calculated. RESULTS: The Lysholm score improved
      significantly from 59.8 +/- 12.9 at baseline to 86.1 +/- 15.7 at the second visit
      (p < 0.01). The mean global T1 of the repair tissue (1st visit 581.3 +/- 126.4
      ms; 2nd visit 684.1 +/- 169.9 ms; p = 0.104) and the mean relative T1 value
      showed stable results over one year (1st visit 0.81 +/- 0.28; 2nd visit 0.76 +/-
      0.32; p = 0.4). CONCLUSIONS: The study demonstrated stable glycosaminoglycan
      content of the repair tissue after MACT at midterm.

PMID- 23161109
TI  - Minimally invasive plate osteosynthesis of distal tibial fracture using a
      posterolateral approach: a cadaveric study and preliminary report.
AB  - PURPOSE: The aims of this anatomical study were to evaluate the feasibility of
      minimally invasive plate osteosynthesis (MIPO) using a posterolateral approach in
      distal tibial fractures and to study the relationship between neurovascular
      structures and the plate. METHODS: Two separate incisions, one proximal and one
      distal, were made on the posterolateral aspect of ten cadaveric legs in the prone
      position. A 14-hole contralateral anterolateral distal tibial locking plate was
      inserted into the submuscular tunnel using a posterolateral approach, and one
      screw was fixed on each side of the proximal and distal tibia. The MIPO tunnel
      was then explored to identify the relationship between neurovascular bundles and
      plate. RESULTS: For the proximal incision, retraction of the flexor hallucis
      longus and the tibialis posterior muscles medially was very important because it
      could protect the posterior tibial artery and the tibial nerve during plating.
      The sural nerve and lesser saphenous vein were easily identified and retracted in
      the superficial layer of the distal incision. In addition, we achieved
      satisfactory outcomes after using this MIPO technique in one patient. CONCLUSION:
      Based on the results of our study, it seems that using the MIPO technique through
      a posterolateral approach should be a reasonable and safe treatment option for
      distal tibial fractures, especially when the anterior soft tissue is compromised.
      However, studies with a higher level of evidence should be done in more patients
      to confirm the clinical safety of using this technique.

PMID- 23161110
TI  - Solvent-free melt electrospinning for preparation of fast dissolving drug
      delivery system and comparison with solvent-based electrospun and melt extruded
      systems.
AB  - The solvent-free melt electrospinning (MES) method was developed to prepare a
      drug delivery system with fast release of carvedilol (CAR), a drug with poor
      water solubility. To the authors knowledge, this is the first report for
      preparing drug-loaded melt electrospun fibers. Cationic methacrylate copolymer of
      Eudragit(r) E type was used as a fiber forming polymer matrix. For comparison,
      ethanol-based electrospinning and melt extrusion (EX) methods were used to
      produce samples that had the same composition as the melt electrospun system.
      According to the results of scanning electron microscopy, X-ray diffraction,
      differential scanning calorimetry, and Fourier transformed infrared spectrometry
      investigations, amorphous solid nanodispersions/solutions of CAR in Eudragit(r) E
      matrix were obtained in all cases with 20 m/m % drug content. In vitro drug
      release in acidic media from the extrudates was significantly faster (5 min) than
      that from crystalline CAR. Moreover, ultrafast drug release was achieved from the
      solvent-free melt and ethanol-based electrospun samples because of their huge
      surface area and the soluble polymer matrix in the acidic media. These results
      demonstrate that solvent-free MES is a promising, novel technique for the
      production of drug delivery systems with enhanced dissolution because it can
      combine the advantages of EX (e.g., solvent-free, continuous process, and
      effective amorphization) and solvent-based electrospinning (huge product surface
      area).

PMID- 23161111
TI  - Detrimental effects of proteasome inhibition activity in Drosophila melanogaster:
      implication of ER stress, autophagy, and apoptosis.
AB  - In eukaryotes, the ubiquitin-proteasome machinery regulates a number of
      fundamental cellular processes through accurate and tightly controlled protein
      degradation pathways. We have, herein, examined the effects of proteasome
      functional disruption in Dmp53 (+/+) (wild-type) and Dmp53 (-/-) Drosophila
      melanogaster fly strains through utilization of Bortezomib, a proteasome-specific
      inhibitor. We report that proteasome inhibition drastically shortens fly life
      span and impairs climbing performance, while it also causes larval lethality and
      activates developmentally irregular cell death programs during oogenesis.
      Interestingly, Dmp53 gene seems to play a role in fly longevity and climbing
      ability. Moreover, Bortezomib proved to induce endoplasmic reticulum (ER) stress
      that was able to result in the engagement of unfolded protein response (UPR)
      signaling pathway, as respectively indicated by fly Xbp1 activation and Ref(2)P
      containing protein aggregate formation. Larva salivary gland and adult brain both
      underwent strong ER stress in response to Bortezomib, thus underscoring the
      detrimental role of proteasome inhibition in larval development and brain
      function. We also propose that the observed upregulation of autophagy operates as
      a protective mechanism to "counterbalance" Bortezomib-induced systemic toxicity,
      which is tightly associated, besides ER stress, with activation of apoptosis,
      mainly mediated by functional Drice caspase and deregulated dAkt kinase. The
      reduced life-span of exposed to Bortezomib flies overexpressing Atg1_RNAi or
      Atg18_RNAi supports the protective nature of autophagy against proteasome
      inhibition-induced stress. Our data reveal the in vivo significance of proteasome
      functional integrity as a major defensive system against cellular toxicity likely
      occurring during critical biological processes and morphogenetic courses.

PMID- 23161112
TI  - Stress reaction of kidney epithelial cells to inorganic solid-core nanoparticles.
AB  - A route of accumulation and elimination of therapeutic engineered nanoparticles
      (NPs) may be the kidney. Therefore, the interactions of different solid-core
      inorganic NPs (titanium-, silica-, and iron oxide-based NPs) were studied in
      vitro with the MDCK and LLC-PK epithelial cells as representative cells of the
      renal epithelia. Following cell exposure to the NPs, observations include
      cytotoxicity for oleic acid-coated iron oxide NPs, the production of reactive
      oxygen species for titanium dioxide NPs, and cell depletion of thiols for
      uncoated iron oxide NPs, whereas for silica NPs an apparent rapid and short-lived
      increase of thiol levels in both cell lines was observed. Following cell exposure
      to metallic NPs, the expression of the tranferrin receptor/CD71 was decreased in
      both cells by iron oxide NPs, but only in MDCK cells by titanium dioxide NPs. The
      tight association, then subsequent release of NPs by MDCK and LLC-PK kidney
      epithelial cells, showed that following exposure to the NPs, only MDCK cells
      could release iron oxide NPs, whereas both cells released titanium dioxide NPs.
      No transfer of any solid-core NPs across the cell layers was observed.

PMID- 23161113
TI  - Distinct cerebrospinal fluid amyloid-beta peptide signatures in cognitive decline
      associated with Alzheimer's disease and schizophrenia.
AB  - Mild alterations in cognitive function are present in normal aging and severe
      cognitive alterations are a hallmark of Alzheimer's disease (AD). Cognitive
      deficits are prevalent in patients with schizophrenia (SCZ) and worsen with old
      age. We recently reported that elderly SCZ patients show reduced levels of
      amyloid-beta (Abeta)1-42 in cerebrospinal fluid (CSF). To further clarify the
      role of Abeta in cognitive decline, we analyzed the whole panel of CSF Abeta
      isoforms in elderly SCZ patients as well as in sporadic AD using SELDI TOF MS.
      The immunoproteomic study revealed, in all analyzed CSF samples, the presence of
      15 different Abeta peptides. In CSF from SCZ, we detected an overall strong
      reduction of almost all Abeta species while in sporadic AD Abeta1-42 was the only
      peptide reduced. A significant independent association between Abeta1-40 levels
      and global cognition was found in SCZ. In addition, in SCZ patients, duration of
      therapy was positively associated with soluble amyloid precursor protein alpha
      levels, the total amount of CSF Abeta and the most abundant Abeta1-40 isoform.
      These data suggests a dysmetabolism of amyloid precursor protein in older SCZ
      patients. Thus, the quite comparable reduction of CSF Abeta1-42 in AD and in
      elderly SCZ patients reflects different pathophysiological dynamics in ageing
      brain.

PMID- 23161114
TI  - Utility of 18F-FDG PET/CT for detecting neck metastasis in patients with salivary
      gland carcinomas: preoperative planning for necessity and extent of neck
      dissection.
AB  - BACKGROUND: The precise diagnosis of cervical lymph node metastasis (CLNM) of
      salivary gland cancer is important to determine the surgical extent and adjuvant
      therapy. This study assessed the clinical utility of (18)F-FDG PET in identifying
      CLNM in such patients. METHODS: Fifty-four patients with intermediate or high
      grade salivary gland cancer were preoperatively evaluated with (18)F-FDG PET/CT
      and CT/MRI. Histopathologic analysis of neck dissection tissues was used as the
      gold standard for assessing imaging techniques. Tumor and nodal maximum
      standardized uptake values (SUVmax) were measured for each patient. Univariate
      and multivariate analyses were used to identify CLNM predictive factors. RESULTS:
      Of the 54 patients, 24 patients (44%) had CLNM. On a per-patient basis, the
      sensitivity and specificity of (18)F-FDG PET/CT and CT/MRI were not significantly
      different (92 vs. 83%, P = 0.625 and 93 vs. 97%, P = 1.000, respectively). On a
      per-level basis, (18)F-FDG PET/CT was significantly more sensitive and accurate
      than CT/MRI in the ipsilateral neck (96 vs. 54%, P < 0.001 and 92 vs. 83%, P <
      0.001, respectively). The mean nodal SUVmax values of patients with and without
      nodal metastasis were 4.9 and 2.1, respectively (P = 0.008). Histologic grade was
      a significant predictor of CLNM (P = 0.014, odds ratio 14.46, 95% confidence
      interval 1.73-120.79). CONCLUSIONS: (18)F-FDG PET/CT imaging and histologic grade
      are useful for detecting CLNM in patients with salivary gland carcinoma. This
      finding may guide preoperative planning for the necessity and extent of neck
      dissection in these patients.

PMID- 23161115
TI  - Blurry boundaries: do epithelial borderline lesions of the breast and ductal
      carcinoma in situ have similar rates of subsequent invasive cancer?
AB  - BACKGROUND: The histology of epithelial "borderline lesions" of the breast, which
      have features in between atypical ductal hyperplasia (ADH) and ductal carcinoma
      in situ (DCIS), is well described, but the clinical behavior is not. This study
      reports subsequent ipsilateral breast events (IBE) in patients with borderline
      lesions compared with those with DCIS. METHODS: Patients undergoing breast
      conserving surgery for borderline lesions or DCIS from 1997 to 2010 were
      identified from a prospective database. IBE was defined as the diagnosis of
      subsequent ipsilateral DCIS or invasive ductal carcinoma. RESULTS: A total of 143
      borderline-lesion patients and 2,328 DCIS patients were identified. Median follow
      up was 2.9 and 4.4 years, respectively. 7 borderline-lesion and 172 DCIS patients
      experienced an IBE. 5 year IBE rates were 7.7 % for borderline lesions and 7.2 %
      for DCIS (p = .80). 5 year invasive IBE rates were 6.5 and 2.8 %, respectively (p
      = .25). Similarly, when analyses were restricted to patients who did not receive
      radiotherapy, or endocrine therapy, or both, borderline-lesion and DCIS patients
      did not demonstrate statistically significant differences in rates of IBE or
      invasive IBE. CONCLUSIONS: When compared with DCIS, borderline lesions do not
      demonstrate lower rates of IBE or invasive IBE. Despite "borderline" histology, a
      5 year IBE rate of 7.7 % and an invasive IBE rate of 6.5 % suggest that the risk
      of future carcinoma is significant and similar to that of DCIS.

PMID- 23161117
TI  - Efficacy and toxicity of (chemo)radiotherapy for primary subglottic cancer.
AB  - BACKGROUND AND PURPOSE: Primary subglottic cancer is a rare malignancy. We
      investigated the efficacy and toxicity of radiotherapy for subglottic cancer.
      PATIENTS AND METHODS: Nineteen patients with primary squamous cell carcinoma of
      the subglottis received radiotherapy, 14 of whom also underwent chemotherapy. Of
      the 19 patients, 15 received definitive radiotherapy to the gross tumors with
      total doses of 70-70.2 Gy in 35-39 fractions, and 4 underwent preoperative
      radiotherapy with total doses of 37.8-55.8 Gy in 21-31 fractions, followed by
      total laryngectomy. RESULTS: Of the 19 patients, 5 developed local progression
      and 2 developed distant metastasis at the median follow-up period of 5 years. The
      5-year local control and disease-free rates were 74 and 63%, respectively. Three
      patients died of tumor progression, and the 5-year overall and disease-free
      survival rates were 80 and 63%, respectively. Regarding acute toxicities,
      transient mucositis and dermatitis of grade 3 or lower were observed in all
      patients, but there were no late toxicities of grade 3 or higher. CONCLUSION:
      Radiotherapy is a safe and effective treatment for patients with primary squamous
      cell carcinoma of the subglottis. The use of chemotherapy together with
      radiotherapy may enhance treatment efficacy and contribute to larynx preservation
      through good local control.

PMID- 23161118
TI  - Can treatment of pediatric Hodgkin's lymphoma be improved by PET imaging and
      proton therapy?
AB  - BACKGROUND AND PURPOSE: To explore a new positron emission tomography (PET)-based
      target concept for pediatric Hodgkin's lymphoma (PHL). PATIENTS AND METHODS: For
      10 patients, the planning target volume PTV1 was based on initial CT tumor
      extension and PTV2 on anatomy-related PET-positive lymph node levels after
      chemotherapy. The treatment techniques investigated (prescribed dose 19.8 Gy)
      comprised opposed-field (2F), intensity-modulated photon (IMXT), and single-field
      (PS) proton techniques. Treatment concepts were compared concerning dose-volume
      histogram (DVH) parameters and organ-equivalent doses (OED). RESULTS: The median
      PTV1 and PTV2 were 902 +/- 555 cm(3) and 281 +/- 228 cm(3). When using PTV2
      instead of PTV1 for all techniques, the D(2%) of the heart was reduced from 14 to
      9 Gy and the D(mean) of the thyroid from 16.6 to 2.7 Gy. Low- (20%), median-
      (50%), and high-dose volumes (80%) were reduced by 60% for the heart and bones
      using PTV2. PS reduced the high-dose volume of the lungs and the heart by up to
      60%. IMXT increased the low-dose volumes and OED. PTV2 reduced OED by 54 +/- 10%
      for all organs at risk. CONCLUSION: PTV2 has a high impact on the treated volume
      and on sparing of organs at risk. The combination of an adaptive target volume
      definition with protons could contribute to future PHL treatment concepts.

PMID- 23161119
TI  - Influence of osteopontin silencing on survival and migration of lung cancer
      cells.
AB  - BACKGROUND AND PURPOSE: Osteopontin (OPN) is a multifunctional protein
      overexpressed in many cancers and is involved in tumor progression and
      metastasis. In lung cancer, elevated OPN expression is associated with an
      unfavorable prognosis. Therefore, inhibition of OPN is an attractive approach for
      improving survival. MATERIALS AND METHODS: We used siRNA to specifically
      downregulate OPN expression in A549 lung cancer cells. OPN silencing was
      evaluated with quantitative reverse transcriptase polymerase chain reaction (RT
      PCR) for mRNA levels and with Western blotting for protein levels. Effects on
      cell proliferation were measured by cell counting. The influence on tumor cell
      migration was detected using a modified Boyden chamber. Changes in cell cycle
      distribution were assessed by flow cytometry. Using the colony formation assay,
      we determined changes in radiosensitivity. RESULTS: A specific and effective
      downregulation of OPN expression was detected in both RNA and protein levels.
      Cell proliferation and cell migration were significantly reduced by OPN silencing
      after 24 h and the effects were further increased by the addition of irradiation.
      The cell cycle distribution showed a reduction in S phase and an increase in
      cells arrested in both G(0)/G(1) and G(2)/M phases. Specific enhancement of
      radiosensitivity was clearly shown after OPN knockdown. CONCLUSION: The
      combination of OPN silencing and irradiation showed a synergistic effect leading
      to reduced cell survival.

PMID- 23161120
TI  - Proxy assessment of patients before and after radiotherapy for brain metastases.
      Results of a prospective study using the DEGRO brain module.
AB  - PURPOSE: Proxies of patients with poor performance status could give useful
      information about the patients' quality of life (QoL). We applied a newly
      developed questionnaire in a prospective QoL study of patients undergoing
      radiotherapy for brain metastases in order to make the first move to validate
      this instrument, and we compared the results with scores obtained using validated
      patient-completed instruments. MATERIALS AND METHODS: From January 2007 to June
      2010,  166 patients with previously untreated brain metastases were recruited at
      14 centers in Germany and Austria. The EORTC-QLQ-C15-PAL and the brain module
      BN20 were used to assess QoL in patients at the start of treatment and 3 months
      later. At the same time points, 141 of their proxies estimated the QoL with the
      new DEGRO brain module (DBM), a ten-item questionnaire rating the general
      condition as well as functions and impairment by symptoms in areas relevant to
      patients with brain metastases. RESULTS: At 3 months, 85 of 141 patients (60%)
      with initial response by a proxy were alive. Sixty-seven of these patients (79%
      of 3-month survivors) and 65 proxies completed the second set of questionnaires.
      After 3 months, QoL significantly deteriorated in all items of proxy-assessed QoL
      except headache. Correlations between self-assessed and proxy-assessed QoL were
      high in single items such as nausea, headache, and fatigue. CONCLUSIONS: The high
      correlation between self-assessment and proxy ratings as well as a similar change
      over time for both approaches suggest that in patients with brain metastases,
      proxy assessment using the DBM questionnaire can be an alternative approach to
      obtaining QoL data when patients are unable to complete questionnaires
      themselves. Our self-constructed and first applied DBM is the only highly
      specific instrument for patients with brain metastases, but further tests are
      needed for its final validation.

PMID- 23161121
TI  - Benefit of replacing the Sigma-60 by the Sigma-Eye applicator. A Monte Carlo
      based uncertainty analysis.
AB  - BACKGROUND AND PURPOSE: To investigate the clinical benefit of replacing the BSD
      2000 Sigma-60 with the Sigma-Eye applicator, taking into account effects of
      uncertainties in tissue and water bolus parameters. PATIENTS AND METHODS: For 20
      patients, specific absorption rate (SAR) and temperature distributions were
      calculated and optimized, based on computed tomography (CT) scans in treatment
      position. The impact of uncertainties on predicted distributions was studied
      using a Monte Carlo uncertainty assessment. RESULTS: Replacing the Sigma-60 by
      the Sigma-Eye applicator resulted in a higher SAR in the tumor [on average a
      decrease of the hotspot tumor quotient (HTQ) by 24%; p < 0.001], and higher
      temperatures (T90: +0.4 degrees C, p < 0.001; T50: +0.6 degrees C, p < 0.001)
      using literature values and SAR optimization. When temperature optimization (T90)
      was used, a larger average increase was found (T90: +0.7 degrees C, p < 0.001;
      T50: +0.8 degrees C, p < 0.001). When taking into account uncertainties, a
      decrease of 23% in median HTQ (p < 0.001) and an increase in T50 and T90 of 0.4
      degrees C (p < 0.001) could be demonstrated. CONCLUSION: Based on this
      uncertainty analysis, significant and clinically relevant improvements in HTQ and
      tumor temperature were achieved when replacing the Sigma-60 by the Sigma-Eye
      applicator.

PMID- 23161122
TI  - Accurate estimation of dose distributions inside an eye irradiated with 106Ru
      plaques.
AB  - BACKGROUND: Irradiation of intraocular tumors requires dedicated techniques, such
      as brachytherapy with (106)Ru plaques. The currently available treatment planning
      system relies on the assumption that the eye is a homogeneous water sphere and on
      simplified radiation transport physics. However, accurate dose distributions and
      their assessment demand better models for both the eye and the physics. METHODS:
      The Monte Carlo code PENELOPE, conveniently adapted to simulate the beta decay of
      (106)Ru over (106)Rh into (106)Pd, was used to simulate radiation transport based
      on a computerized tomography scan of a patient's eye. A detailed geometrical
      description of two plaques (models CCA and CCB) from the manufacturer BEBIG was
      embedded in the computerized tomography scan. RESULTS: The simulations were
      firstly validated by comparison with experimental results in a water phantom.
      Dose maps were computed for three plaque locations on the eyeball. From these
      maps, isodose curves and cumulative dose-volume histograms in the eye and for the
      structures at risk were assessed. For example, it was observed that a 4-mm
      anterior displacement with respect to a posterior placement of a CCA plaque for
      treating a posterior tumor would reduce from 40 to 0% the volume of the optic
      disc receiving more than 80 Gy. Such a small difference in anatomical position
      leads to a change in the dose that is crucial for side effects, especially with
      respect to visual acuity. The radiation oncologist has to bring these large
      changes in absorbed dose in the structures at risk to the attention of the
      surgeon, especially when the plaque has to be positioned close to relevant
      tissues. CONCLUSION: The detailed geometry of an eye plaque  in computerized and
      segmented tomography of a realistic patient phantom was simulated accurately.
      Dose-volume histograms for relevant anatomical structures of the eye and the
      orbit were obtained with unprecedented accuracy. This represents an important
      step toward an optimized brachytherapy treatment of ocular tumors.

PMID- 23161123
TI  - Modified silver staining in 2DE improves protein detection even at extremely low
      sample concentration.
AB  - The typical concentration of protein loaded varies from 0.13 to 1.40 MUg/MUL for
      a classical silver staining method in 2DE gel. Here, we present a simple modified
      classical silver staining method by modifying the silver impregnation and
      development reaction steps. This modified method detects the protein spots at
      extremely low loaded concentrations, ranging from 0.0048 to 0.0480 MUg/MUL. We
      recommend this modified silver staining as an excellent method for the limited
      biological samples used for silver-stained 2DE analysis. Altogether, the protocol
      takes close to two days from first dimension separation to second dimension
      separation, followed by silver staining, scanning, and analysis.

PMID- 23161124
TI  - Pharmaceutical care program for type 2 diabetes patients in Brazil: a randomised
      controlled trial.
AB  - BACKGROUND: Brazilians with type 2 diabetes require action to improve haemoglobin
      A1C levels considering the fact that approximately 73 % of them have poor
      glycaemic control. Evidence has shown the potential benefits of pharmaceutical
      care programs in type 2 diabetes patients. OBJECTIVE: To evaluate the effect of a
      pharmaceutical care program on blood glucose, blood pressure and lipid profile in
      hyperglycaemic patients undergoing drug treatment for type 2 diabetes. SETTING:
      Six primary care units of the Brazilian public health system, Ouro Preto, Brazil.
      METHOD: An open, randomised, controlled clinical trial was conducted for 6
      months. Subjects aged 18 years or older who were using oral antidiabetic
      medications and presenting haemoglobin A1C levels >=7 % were randomly assigned to
      receive only usual health care or usual health care plus pharmaceutical
      intervention. Main outcome measure Haemoglobin A1C. RESULTS: A total of 129
      subjects were enrolled, and 100 patients completed the study. Compared to the
      control group (n = 50), the intervention group (n = 50) showed a significant
      reduction of haemoglobin A1C (-0.6 vs 0.7 %, p = 0.001), fasting plasma glucose,
      total cholesterol, LDL cholesterol, triglycerides and systolic blood pressure and
      a significant increase in HDL cholesterol and the use of lipid-modifying agents
      and platelet aggregation inhibitors. CONCLUSIONS: This study suggests that a
      pharmaceutical care program may provide important contributions to reduce
      haemoglobin A1C in type 2 diabetes patients. Moreover, the promotion of the
      rational use of drugs may be better achieved in a context of pharmaceutical care
      programs in Brazil.

PMID- 23161126
TI  - Maintaining lasting improvements: one-year follow-up of children with severe
      chronic pain undergoing multimodal inpatient treatment.
AB  - OBJECTIVE: To investigate the long-term effectiveness of a 3-week multimodal
      inpatient program for children and adolescents with chronic pain. METHODS: 167
      adolescents were evaluated at pretreatment baseline, 3-, and 12-month follow-up.
      Long-term effectiveness was investigated for pain-related variables (pain-related
      disability, school absence, pain intensity) and emotional distress. RESULTS: We
      found statistically and clinically significant changes in all variables. After 1
      year, the majority (56%) showed overall improvement as indexed by decreased pain
      related disability or school absence. 22% had an unsuccessful treatment outcome.
      Those showing only short-term improvements had higher levels of emotional
      distress at baseline. CONCLUSIONS: 1 year after completing a multimodal inpatient
      program adolescents report less chronic pain, disability, and emotional distress.
      Clinically significant changes remain stable. Adolescents with high levels of
      emotional distress at admission may require special attention to maintain
      positive treatment outcomes. Specialized inpatient therapy is effective for
      children with chronic pain.

PMID- 23161125
TI  - Preadolescent temperament and risky behavior: bicycling across traffic-filled
      intersections in a virtual environment.
AB  - OBJECTIVE: This investigation used a bicycling simulator to examine how
      preadolescent temperament is related to risky behavior. METHODS: Children aged 10
      and 12 years (N = 109) rode a bicycle through a virtual environment where they
      crossed intersections with continuous cross traffic. Mothers filled out the Early
      Adolescent Temperament Questionnaire-Revised. RESULTS: Older children and male
      participants timed their entry into the intersection more precisely than did
      younger children and female participants, as did 10-year-old children higher in
      inhibitory control and 10-year-old boys higher in aggression. However, only 10
      year-old children higher in inhibitory control had more time to spare when they
      cleared the intersection. For 10-year-old boys higher in aggression, cutting in
      more closely behind the lead vehicle was accompanied by less stopping at
      intersections, less waiting before crossing, and choosing smaller gaps to cross.
      CONCLUSIONS: The Discussion section focuses on inhibitory control as a protective
      factor and aggression as a risk factor for car-bicycle collisions.

PMID- 23161127
TI  - Micellar electrokinetic chromatography: a review of methodological and
      instrumental innovations focusing on practical aspects.
AB  - This review article addresses recent methodological and instrumental innovations
      in MEKC with emphasis on practical aspects. Like its predecessors, this review is
      intended to provide an updated overview covering work on the most salient
      methodological contributions to enhancing sensitivity and resolution in MEKC
      based determinations published over the past two years. The most widespread
      approaches to enhancing sensitivity, which include improving "classical" online
      sample concentration techniques, combinations of on- and off-line sample
      concentration protocols and recent developments are discussed, and so are
      modifications of existing MEKC systems with various micellar phases, the use of
      BGE additives (organic modifiers, chiral selectors, gold nanoparticles) and
      coated capillaries, and the implementation of 2D separations and chemometric
      methods to enhance resolution. Instrumental approaches such as MS and LIF are
      also discussed, and proposals for overcoming the problems typically encountered
      in directly coupling MEKC with MS, and the recent inception of quantum dots with
      a great potential for LIF detection in MEKC, are also dealt with. Finally,
      foreseeable developments on potential future directions are also expressed.

PMID- 23161128
TI  - Productivity and equilibrium in simple biofilm models.
AB  - Biofilms are dense, sessile collections of microorganisms with complicated
      internal structures. However, in many applications internal details are less
      important, rather basic, averaged information such as overall community
      productivity are of most interest. This paper studies averaged community
      functions in the context of one dimensional, single species, single limiting
      substrate biofilm models. In particular, using a derived formula for flux of
      substrate into the biofilm as a function of biofilm height and substrate loading,
      overall community production can be calculated and system equilibria can be
      characterized. Consequences for equilibria dependence on a number of mechanisms
      for balancing growth are considered.

PMID- 23161129
TI  - A model for fluid drainage by the lymphatic system.
AB  - This study investigates the fluid flow through tissues where lymphatic drainage
      occurs. Lymphatic drainage requires the use of two valve systems, primary and
      secondary. Primary valves are located in the initial lymphatics. Overlapping
      endothelial cells around the circumferential lining of lymphatic capillaries are
      presumed to act as a unidirectional valve system. Secondary valves are located in
      the lumen of the collecting lymphatics and act as another unidirectional valve
      system; these are well studied in contrast to primary valves. We propose a model
      for the drainage of fluid by the lymphatic system that includes the primary valve
      system. The analysis in this work incorporates the mechanics of the primary
      lymphatic valves as well as the fluid flow through the interstitium and that
      through the walls of the blood capillaries. The model predicts a piecewise linear
      relation between the drainage flux and the pressure difference between the blood
      and lymphatic capillaries. The model describes a permeable membrane around a
      blood capillary, an elastic primary lymphatic valve and the interstitium lying
      between the two.

PMID- 23161130
TI  - ER-bound steps in the biosynthesis of G protein-coupled receptors.
AB  - The polypeptide of a G protein-coupled receptor is inserted into the membrane of
      the endoplasmic reticulum while being translated and this process by itself may
      be sufficient to establish the proper receptor fold. X-ray structures reveal a
      common polypeptide topology with little variation in the alignment and
      orientation of the seven transmembrane segments, the proximal carboxyl terminus
      (C-tail) and parts of the extracellular loops. These define a structural core the
      stability of which probably represents a major criterion for the receptor to pass
      endoplasmic reticulum (ER) quality control; point mutations affecting the
      structure of the core have an extraordinary chance of causing receptor retention.
      In contrast, cytoplasmic loops 2 and 3 and the distal C-tail are poorly ordered
      at least in the absence of an interaction partner. Similarly, the amino terminal
      tail of rhodopsin-related receptors (but not of receptor subtypes where ligand
      binding requires a stable fold of the N-tail) is unlikely to establish a stable
      fold. These segments can cause ER retention when mutated to inappropriately
      expose hydrophobic peptide patches; to prevent protein aggregation chaperone
      molecules attach to them thus initiating selection for ER-associated degradation.
      It is less clear however if there are additional mechanisms to specifically
      survey the transmembrane core at the level of the lipid bilayer or if
      insufficient packing is detected due to misalignment of the cytoplasmic or
      extracellular face of the receptor.

PMID- 23161131
TI  - Role of chaperones in G protein coupled receptor signaling complex assembly.
AB  - G protein coupled receptors are involved in highly efficient and specific
      activation of signaling pathways. Yet, we do not fully understand the processes
      required to assemble the different partners of the GPCR signaling complex. In
      order to address this issue, we need to understand how receptors and their
      signaling -partners are synthesized, folded and regulated during quality control
      steps in order to generate functional proteins. Several molecular chaperones are
      involved in this process for most proteins, including GPCRs. Several membrane
      proteins require the assembly of different subunits to be functional. In recent
      years, GPCRs have been shown to form oligomers, which could be interpreted as
      subunits of a larger complex. Yet, those oligomers would not be functional
      without the association of other signaling partners; thus, there is a requirement
      for the specific assembly of the -different partners. In this chapter, we will
      cover some aspects of the current knowledge about how chaperones are involved in
      both the formation of GPCR oligomers and in the assembly of the receptors with
      their signaling complex components.

PMID- 23161132
TI  - GPCR oligomerization: contribution to receptor biogenesis.
AB  - G protein-coupled receptor (GPCR) export to the plasma membrane is considered to
      follow the default secretory pathway. Several observations indicate that
      trafficking from the endoplasmic reticulum to the plasma membrane is strictly
      regulated and involves interactions with specific proteins, such as resident ER
      chaperones. These interactions help with GPCR folding, but more importantly, they
      ensure that only properly folded proteins proceed from the ER to the trans-golgi
      network. The assembly of several GPCRs into a quaternary structure is started in
      the ER, before cell surface delivery, and helps in the correct expression of the
      GPCRs. This review will mainly focus on the role of GPCR oligomerization in
      receptor biogenesis.

PMID- 23161133
TI  - The functional size of GPCRs - monomers, dimers or tetramers?
AB  - In almost 16 years since the word "dimer" was used in a publication to describe
      the organization of G protein-coupled receptors (GPCRs), a large number of
      studies have since weighed in on this notion. Are native, functional GPCRs
      monomers, dimers or as some would suggest even higher order structures? Here, we
      review some of the latest evidence regarding the organization of these receptors
      in both homo- and hetero-oligomeric formats, with a particular focus on beta
      adrenergic receptors. This is particularly important for understanding the
      allosteric nature of receptor/receptor interactions. It is likely that, over the
      course of evolution, mechanisms have come into play using all of the possible
      variations in receptor/receptor stoichiometry, depending on the cell and the
      physiological context in question. Finally, we provide some data that suggests
      that higher order structures of GPCRs, as with dimers themselves are probably
      assembled in the ER.

PMID- 23161135
TI  - Regulated GPCR trafficking to the plasma membrane: general issues and the CCR5
      chemokine receptor example.
AB  - The regulated export of nascent G protein coupled receptors (GPCRs) from
      intracellular stores is an emerging concept with important implications in cell
      biology and pharmacology. This phenomenon requires a complex network of
      interactions between GPCRs with either chaperones and escort proteins or
      gatekeepers, which are respectively involved in the progression of GPCRs along
      the biosynthetic pathway to the plasma membrane or in their retention in
      intracellular compartments. The regulated export of GPCRs is also controlled by
      external stimuli and might represent an adaptive mechanism to specific
      physiological constraints, such as the sustained activation of the CCR5 chemokine
      receptor in the context of chemotaxis.

PMID- 23161134
TI  - Regulation of post-Golgi traffic of G protein-coupled receptors.
AB  - Anterograde trafficking of newly synthesized G protein-coupled -receptors (GPCRs)
      from the endoplasmic reticulum to the cell surface represents a crucial
      checkpoint in controlling the amount of the functional receptors at the cell
      surface and the strength of signaling initiated by the receptors. In contrast to
      the extensively studied, well-understood endocytic and recycling pathways, the
      molecular mechanisms underlying the cell-surface targeting of the receptors
      remain poorly defined. In this chapter, I will discuss current advances in
      understanding post-Golgi transport of GPCRs by focusing on specific motifs or
      sequences that may function as sorting signals regulating export from the Golgi
      and subsequent transport to the plasma membrane of GPCRs.

PMID- 23161136
TI  - Regulatory processes governing the cell surface expression of LH and FSH
      receptors.
AB  - The LH receptor (LHR) and FSH receptor (FSHR), collectively termed the
      gonadotropin receptors, are members of the Family A of GPCRs. The gonadotropin
      receptors each contain N-linked carbohydrates that are not directly involved in
      hormone binding, but contribute to the proper folding, and therefore, cell
      surface expression of the receptor. Loss-of-function mutations of an LHR or FSHR
      results in decreased target cell responsiveness. Most inactivating mutations
      cause receptor misfolding, resulting in the retention of the mutant in its
      immature form in the endoplasmic reticulum. A membrane-permeable allosteric
      agonist of the LHR has been shown to serve as a pharmacological chaperone for
      misfolded and intracellularly retained LHRs by promoting their cell surface
      expression. Wild-type LHR and FSHR each form homodimers and heterodimers while in
      the ER. Therefore, when wild-type receptor is co-expressed with a misfolded
      mutant, the misfolded receptor dimerizes with immature wild-type receptor in the
      ER, causing a dominant-negative effect on cell surface expression of the mature
      wild-type receptor. Notably, the propensity for homodimerization is not affected
      by the activation status of the receptor. However, within a receptor dimer, the
      activity of one protomer may allosterically regulate the other protomer.
      Therefore, the dimerization of the gonadotropin receptors appears to be an
      obligate process that is part of the normal itinerary for trafficking to the cell
      surface and, once there, the dimerized receptors allow for additional modulations
      of cell signaling.

PMID- 23161137
TI  - Chaperone-mediated assembly of G protein complexes.
AB  - G protein signaling depends on the ability of the individual subunits of the G
      protein heterotrimer to assemble into functional complexes. Formation of the G
      protein betagamma (Gbetagamma) dimer is particularly challenging because it is an
      obligate dimer in which the individual subunits are unstable on their own. Recent
      studies have revealed an intricate chaperone system that brings the Gbeta and
      Ggamma subunits together. This system includes the cytosolic chaperonin
      containing TCP-1 (CCT) and its co-chaperone phosducin-like protein 1 (PhLP1). CCT
      assists Gbeta in achieving its beta-propeller structure, while PhLP1 releases
      Gbeta from CCT and facilitates its interaction with Ggamma. Once Gbetagamma is
      formed, PhLP1 remains bound until it is displaced by the Galpha subunit and the G
      protein heterotrimer is brought together. Another obligate dimer is the complex
      between the G protein beta(5) subunit and a regulator of G protein signaling
      protein (Gbeta(5)-RGS). Gbeta(5)-RGS also requires CCT for Gbeta(5) folding, but
      PhLP1 plays a different role. It stabilizes the interaction between Gbeta(5) and
      CCT, perhaps to increase folding efficiency. After Gbeta(5) folding PhLP1 must
      subsequently release, allowing the RGS protein to bind and form the Gbeta(5)-RGS
      dimer directly on CCT. Gbeta(5)-RGS is then freed from CCT to interact with its
      membrane anchoring protein and form a stable complex that turns off the G protein
      signal by catalyzing GTP hydrolysis on Galpha.

PMID- 23161138
TI  - Synthesis and assembly of G protein betagamma dimers: comparison of in vitro and
      in vivo studies.
AB  - The heterotrimeric GTP-binding proteins (G proteins) are the canonical cellular
      machinery used with the approximately 700 G protein-coupled receptors (GPCRs) in
      the human genome to transduce extracellular signals across the plasma membrane.
      The synthesis of the constituent G protein subunits, and their assembly into
      Gbetagamma dimers and G protein heterotrimers, determines the signaling
      repertoire for G-protein/GPCR signaling in cells. These synthesis/assembly 
      processes are intimately related to two other overlapping events in the intricate
      pathway leading to formation of G protein signaling complexes, posttranslational
      modification and intracellular trafficking of G proteins. The assembly of the
      Gbetagamma dimer is a complex process involving multiple accessory proteins and
      organelles. The mechanisms involved are becoming increasingly appreciated, but
      are still incompletely understood. In vitro and in vivo (cellular) studies
      provide different perspectives of these processes, and a comparison of them can
      provide insight into both our current level of understanding and directions to be
      taken in future investigations.

PMID- 23161139
TI  - Preferential assembly of G-alphabetagamma complexes directed by the gamma
      subunits.
AB  - Assembly of the G-alphabetagamma heterotrimer is required for receptor signaling.
      Although much has been learned about the assembly process itself, the identities
      of the G-alphabetagamma combinations that actually exist in physiological setting
      are largely unknown. Moreover, there is uncertainty regarding whether the
      individual subunits associate by a random process, or combine by a regulated
      process to form quasi-stable G-alphabetagamma complexes. In this chapter, we will
      focus on emerging genetic -evidence that supports the latter model. Specifically,
      we will discuss how use of gene targeted mice has revealed preferential assembly
      of the striatal-specific Galpha(olf)beta(2)gamma(7) complex occurs by a
      sequential process that is directed by the gamma(7) subunit. The existence of
      specific G-alphabetagamma complexes responsible for transducing the signals from
      different receptors may have profound implications by providing a possible
      explanation for biased agonism.

PMID- 23161141
TI  - Differential assembly of GPCR signaling complexes determines signaling
      specificity.
AB  - Recent proteomic and biochemical evidence indicates that cellular -signaling is
      organized in protein modules. G protein-coupled receptors (GPCRs) are privileged
      entry points for extracellular signals that are transmitted through the plasma
      membrane into the cell. The adequate cellular response and signaling specificity
      is regulated by GPCR-associated protein modules. The composition of these modules
      is dynamic and might depend on receptor stimulation, the proteome of a given
      cellular context, the subcellular localization of receptor-associated modules,
      the formation of GPCR oligomers and the variation of expression levels of
      components of these modules under physiological, for example circadian rhythm, or
      pathological conditions. The current article will highlight the importance of
      GPCR-associated protein modules as a biochemical basis for signaling specificity.

PMID- 23161142
TI  - GPCR and voltage-gated calcium channels (VGCC) signaling complexes.
AB  - Voltage-gated ion channels are transmembrane proteins that control nerve impulses
      and cell homeostasis. Signaling molecules that regulate ion channel activity and
      density at the plasma membrane must be specifically and efficiently coupled to
      these channels in order to control critical physiological functions such as
      action potential propagation. Although their regulation by G-protein receptor
      activation has been extensively explored, the assembly of ion channels into
      signaling complexes of GPCRs plays a fundamental role, engaging specific
      downstream -signaling pathways that trigger precise downstream effectors. Recent
      work has confirmed that GPCRs can intimately interact with ion channels and serve
      as -chaperone proteins that finely control their gating and trafficking in
      subcellular microdomains. This chapter aims to describe examples of GPCR-ion
      channel co-assembly, focusing mainly on signaling complexes between GPCRs and
      voltage-gated calcium channels.

PMID- 23161140
TI  - G protein trafficking.
AB  - The classical view of heterotrimeric G protein signaling places G -proteins at
      the cytoplasmic surface of the cell's plasma membrane where they are activated by
      an appropriate G protein-coupled receptor. Once activated, the GTP-bound Galpha
      and the free Gbetagamma are able to regulate plasma membrane-localized effectors,
      such as adenylyl cyclase, phospholipase C-beta, RhoGEFs and ion channels.
      Hydrolysis of GTP by the Galpha subunit returns the G protein to the inactive
      Galphabetagamma heterotrimer. Although all of these events in the G protein cycle
      can be restricted to the cytoplasmic surface of the plasma membrane, G protein
      localization is dynamic. Thus, it has become increasingly clear that G proteins
      are able to move to diverse subcellular locations where they perform non
      canonical signaling functions. This chapter will highlight our current
      understanding of trafficking pathways that target newly synthesized G proteins to
      the plasma membrane, activation-induced and reversible translocation of G
      proteins from the plasma membrane to intracellular locations, and constitutive
      trafficking of G proteins.

PMID- 23161143
TI  - Pharmacological chaperones correct misfolded GPCRs and rescue function: protein
      trafficking as a therapeutic target.
AB  - G-protein-coupled receptors (GPCRs) are a large superfamily of plasma membrane
      proteins that play central roles in transducing endocrine, neural and -sensory
      signals. In humans, more than 30 disorders are associated with mutations in GPCRs
      and these proteins are common drug development targets, with 30-50% of drugs
      targeting them. GPCR mutants are frequently misfolded, recognized as defective by
      the cellular quality control system, retained in the endoplasmic reticulum and do
      not traffic to the plasma membrane. The use of small molecules chaperones
      (pharmacological chaperones or "pharmacoperones") to rescue misfolded GPCRs has
      provided a new approach for treatment of human diseases caused by misfolding and
      misrouting. This chapter provides an overview of the molecular basis of this
      approach using the human gonadotropin-releasing hormone receptor (hGnRHR) as
      model for treatment of conformational diseases provoked by -misfolded GPCRs.

PMID- 23161145
TI  - MDR-1 C3435T polymorphism may affect blood pressure in resistant hypertensive
      patients independently of its effects on aldosterone release.
AB  - Aldosterone increases plasma volume and may be involved with resistant
      hypertension. P-glycoprotein is a transporter involved in the distribution and
      disposition of aldosterone, and is encoded by the MDR-1 gene. MDR-1 has
      functional polymorphisms that may affect P-glycoprotein expression. We
      hypothesized that the C(3435)T polymorphism in MDR-1 could be associated with
      resistant hypertension and with changes in hypertension-related parameters. We
      studied 105 healthy volunteers, 137 hypertensive patients responsive to
      treatment, and 83 resistant hypertensive patients. While we found no association
      of C(3435)T genotypes with resistance to treatment (p = 0.31), C allele was
      associated with hypertension (p = 0.03). Furthermore, the CC genotype was
      associated with higher systolic blood pressure (p < 0.01 for both daytime and
      nighttime, respectively) and diastolic blood pressure (p < 0.01 for both daytime
      and nighttime, respectively). This effect was probably independent of
      aldosterone, as we found no differences in aldosterone plasma levels, nor in
      pulse wave velocity (PVW) between the genotypes groups (p = 0.77 and p = 0.48,
      respectively). Our results show an association of C(3435)T with hypertension and
      with blood pressure levels in resistant hypertensive subjects. 

PMID- 23161144
TI  - Antenatal betamethasone exposure alters renal responses to angiotensin-(1-7) in
      uninephrectomized adult male sheep.
AB  - Antenatal corticosteroid exposure reduces renal function and alters the
      intrarenal renin-angiotensin system to favor angiotensin activation of
      angiotensin type 1 receptor (AT1R) mediated responses in ovine offspring. This
      study aimed to assess whether antenatal steroid exposure would affect renal
      responses to the direct intrarenal infusion of angiotensin-(1-7) in rams and the
      angiotensin receptors involved in mediating responses to the peptide. Adult,
      uninephrectomized rams exposed to either betamethasone or vehicle before birth
      received intrarenal angiotensin-(1-7) infusions (1 ng/kg/min) alone or in
      combination with antagonists to angiotensin receptors for 3 h. Basal sodium
      excretion (UNa) was significantly lower and mean arterial pressure was
      significantly higher in betamethasone- compared to the vehicle-treated sheep.
      Angiotensin-(1-7) decreased UNa more in betamethasone- than in vehicle-treated
      sheep. Candesartan reversed the response to angiotensin-(1-7) but D-Ala(7)
      angiotensin-(1-7) did not. Angiotensin-(1-7) infusion decreased effective renal
      plasma flow in both groups to a similar extent and the response was reversed by
      candesartan, but was not blocked by D-Ala(7)-angiotensin-(1-7). Glomerular
      filtration rate increased significantly in both groups after 3 h infusion of
      angiotensin-(1-7) plus candesartan. These results suggest that antenatal exposure
      to a clinically relevant dose of betamethasone impairs renal function in rams.
      Moreover, angiotensin-(1-7) appears capable of activating the AT1R in
      uninephrectomized rams. 

PMID- 23161146
TI  - Imidapril provides a protective effect on pulmonary hypertension induced by low
      ambient temperature in broiler chickens.
AB  - OBJECTIVE: The objective of this article is to explore the role of imidapril on
      pulmonary hypertension induced by low ambient temperature in broiler chickens.
      MATERIALS AND METHODS: Ninety chickens were randomly divided into three groups (n
      = 30): a control group, a low-temperature group and an imidapril group. Chickens
      in the low-temperature group and imidapril group were exposed to low ambient
      temperature from 14 days of age until 45 days of age; chickens in the imidapril
      group were gavaged with imidapril 3 mg/kg once daily for 30 days. The pulmonary
      arterial pressure, main pulmonary arterial diameter and pulmonary arterial wall
      thickness were measured, and lung tissue ACE, ACE2 mRNA expression, proliferating
      cell nuclear antigen (PCNA)-positive cells and Ang II, Ang (1-7) concentration
      were evaluated. RESULTS: The pulmonary arterial pressure was higher, the main
      pulmonary arterial diameter was wider and the pulmonary arterial wall was thicker
      in the low-temperature group than those in the control group and the imidapril
      group. ACE mRNA and PCNA-positive cells increased significantly in the low
      temperature group compared with the control group and imidapril group; lung
      tissue Ang II concentration in the low-temperature group was higher, but Ang (1
      7) content was lower than that in the control group and imidapril group.
      CONCLUSION: Imidapril provides a protective effect on pulmonary hypertension
      induced by low ambient temperature in broiler chickens.

PMID- 23161149
TI  - Valgus osteotomy in combination with dynamic hip screw fixation for fibrous
      dysplasia with shepherd's crook deformity.
AB  - BACKGROUND AND OBJECTIVES: The treatment of fibrous dysplasia with shepherd's
      crook deformity is a big challenge. The purpose of this study was to investigate
      the clinical effect of valgus osteotomy in combination with dynamic hip screw
      (DHS) fixation to treat fibrous dysplasia with shepherd's crook deformity.
      METHOD: Twenty-one clinical cases of femoral fibrous dysplasia with shepherd's
      crook deformity treated between April 2001 and May 2010 were retrospectively
      analyzed. The valgus osteotomy and internal fixation were performed for these
      patients. Six patients underwent DHS and trochanter stabilizing plate internal
      fixation, and the other 15 cases were stabilized by DHS fixation. RESULTS:
      Patients were followed for 19-128 months. The neck-shaft angle was corrected from
      89 degrees  (range 65 degrees -107 degrees ) preoperatively to 129 degrees 
      (range 119 degrees -140 degrees ) postoperatively. Limb-length discrepancy was
      corrected from 3.0 (range 1.8-4.5) cm preoperatively to 0.7 (range 0-1.9) cm
      postoperatively. All osteotomies had healed at the final follow-up examination.
      The clinical scores, which were evaluated by the modified criteria of Guille,
      improved from an average of 2.9 (range 1-7) to 8.5 (range 6-10). CONCLUSION: Our
      results demonstrate that valgus osteotomy in combination with DHS internal
      fixation is an easy and effective method for the treatment of fibrous dysplasia
      with shepherd's crook deformity. It can restore the neck-shaft angle and re
      establish the mechanical alignment of the femur to improve function.

PMID- 23161147
TI  - Effects of intracavernous injection of adipose-derived stem cells on cavernous
      nerve regeneration in a rat model.
AB  - The aim of this study was to investigate effects of intracavernous injection of
      adipose-derived stem cells (ADSCs) on cavernous nerve (CN) regeneration and
      functional status in a nerve-crush rat model. Thirty Sprague-Dawley male rats
      were randomly divided into three equal groups: one group underwent sham
      operation, while two groups underwent bilateral CN crush. Crush-injury group was
      treated at the time of injury with intracavernous injection of ADSCs, or injured
      control group with no further intervention. Erectile function was assessed by CN
      electrostimulation after 3 months. Penile tissue and crushed nerves were
      collected for histology. Three months after surgery, in the group that underwent
      bilateral nerve crushing with no further intervention, the functional evaluation
      showed a lower mean maximal intracavernous pressure (ICP) and maximal ICP per
      mean arterial pressure (MAP) with CN stimulation than those in the sham group. In
      the group with an immediate intracavernous injection of ADSCs, the mean maximal
      ICP and maximal ICP/MAP were significantly higher than those in the injured
      control group. Histologically, the group with the intracavernous injection of
      ADSCs had more myelinated axons of CNs and more NADPH-diaphorase-positive nerve
      fibers than the injured control group but fewer than the sham group.
      Intracavernous injection of ADSCs treatment had beneficial effects on the smooth
      muscle/collagen ratio in the corpus cavernosum. These results show that the
      intracavernous injection of ADSCs to the site of CN-crush injury facilitates
      nerve regeneration and recovery of erectile function. Our research indicates that
      penile injection of ADSCs can improve recovery of erectile function in a rat
      model of neurogenic ED.

PMID- 23161148
TI  - Neuroprotection of interleukin-6 against NMDA-induced neurotoxicity is mediated
      by JAK/STAT3, MAPK/ERK, and PI3K/AKT signaling pathways.
AB  - We have previously shown that interleukin-6 (IL-6) has neuroprotective effect
      against N-methyl-D-aspartate (NMDA)-induced excitotoxicity. The current study
      aimed to reveal signal transduction pathways involved in the IL-6
      neuroprotection. Cerebellar granule neurons (CGNs) from postnatal 8-day infant
      rats were exposed to IL-6 (120 ng/ml) for 8 days and stimulated with NMDA (100
      MUM) for 15 or 30 min. Dynamic intracellular Ca(2+) fluorescence intensity,
      cytosolic Ca(2+)-dependent phospholipase A2 (cPLA2) expression, and apoptosis and
      necrosis in cultured CGNs were measured by laser scanning confocal microscope,
      real-time PCR and Western blot, and annexin V-FITC/propidium iodide staining,
      respectively. NMDA stimulation of neurons evoked an intracellular Ca(2+)
      overload, an upregulated expression of cPLA2, and an increase in cell death.
      Chronic IL-6 exposure prevented the NMDA-evoked neuronal Ca(2+) overload, cPLA2
      expression upregulation, and apoptosis and necrosis. Anti-gp130 monoclonal
      antibody (mAb), a blocker of gp130 that is a 130-kDa signal-transducing beta
      subunit of IL-6 receptor complex, blocked these effects of IL-6 preventing NMDA
      neurotoxicity. AG490, PD98059, or LY294002, inhibitors specific for the
      intracellular signals, JAK, MAPK, and PI3K, respectively, partially blocked these
      IL-6 neuroprotective effects. Phosphorylation levels of STAT3, ERK1/2, and AKT,
      the downstream proteins for these enzymes of JAK, MAPK, and PI3K, respectively,
      were elevated by IL-6 pretreatment. The enhanced activation of STAT3, ERK1/2, and
      AKT by IL-6 was abolished by AG490, PD98059, and LY294002, respectively. Anti
      gp130 mAb attenuated the activation of all the three detected signaling
      molecules. The present findings suggest that IL-6 neuroprotection is jointly
      mediated by the cellular signal transduction pathways, gp130-JAK-STAT3, gp130
      MAPK-ERK, and gp130-PI3K-AKT.

PMID- 23161150
TI  - Outcome after severe brain trauma associated with epidural hematoma.
AB  - OBJECTIVE: The aim of this study was to identify factors contributing to outcomes
      after severe traumatic brain injury (TBI) associated with epidural hematoma
      (EDH). METHODS: Between 02/2002 and 4/2010 17 Austrian centers prospectively
      enrolled 863 patients with moderate and severe TBI into observational studies.
      Data on accident, treatment, and outcomes were collected. Data sets from patients
      who had severe TBI (=Glasgow Coma Scale score <9) and EDH were selected. Six
      month outcomes were classified as "favorable" if Glasgow Outcome Scale (GOS)
      scores were 5 or 4, and were classified as "unfavorable" if GOS scores were 3 or
      less. The Rotterdam score was used to classify computed tomography (CT) findings;
      the scores published by Hukkelhoven et al. (J Neurotrauma 22:1025-1039, 2005)
      were used to estimate predicted rates of death and of unfavorable outcomes.
      Univariate (Fisher's exact test, t test, Chi(2)-test) and multivariate (logistic
      regression) statistics were used to identify factors associated with hospital
      mortality and favorable outcome. RESULTS: Of the 738 patients with severe TBI 159
      (21.5 %) had EDH. Of these, 49 (30.8 %) died in the hospital, 21 (13.2 %)
      survived with unfavorable outcome, 82 (51.6 %) with favorable outcome; long-term
      outcome was unknown in 7 survivors (4.4 %). Mortality rates predicted by the
      Rotterdam score showed good correlation with observed mortality rates. According
      to the Hukkelhoven scores, observed/predicted ratios for mortality and
      unfavorable outcome were 0.94 and 0.97, respectively. Age, severity of TBI, and
      neurological status were the main factors influencing outcomes after severe TBI
      associated with EDH. We were unable to demonstrate significant effects of
      treatment factors.

PMID- 23161151
TI  - Clinical implications of coronary pressure measurement after stent implantation.
AB  - This study investigated the effect of fractional flow reserve (FFR) after stent
      implantation on clinical outcomes. Pressurewire measurements and follow-up data
      were obtained after stent implantation. Regarding the end point, target lesion
      revascularization (TLR) occurred in 11 patients (15.9%). Patients with TLR had
      higher frequencies of multiple stenting (54.5 vs. 19.0%, p = 0.01), lower post
      interventional FFRs (0.84 vs. 0.88, p = 0.01), and longer stent lengths (42.20
      vs. 27.69 mm, p = 0.01) than patients without TLR. The post-interventional FFR
      cutoff for TLR was 0.79, although this value had a weak discriminatory ability.
      However, multivariate analysis did not show any significant independent
      predictors of TLR (odds ratio 6.33; confidence interval 0.75-53.4, p = 0.09).
      Post-interventional FFR values were not significantly associated with TLR when a
      sub-analysis was performed in patients who underwent only drug-eluting stent
      (DES) implantation. It was difficult to achieve post-interventional FFRs of 0.9
      or greater. DES implantation eliminated the effect of post-interventional FFR on
      TLR. Post-interventional FFR was not able to predict TLR in the present study.

PMID- 23161152
TI  - Isolation of Langerhans islets by dielectrophoresis.
AB  - The purification of Langerhans islets from fragments of pancreatic exocrine
      tissue is a critical stage for the further transplantation of insulin secreting
      islets in patients affected by type I diabetes. Aim of our work was the
      evaluation of dielectrophoresis as a promising method for pancreatic islets
      isolation without physical contact in miniaturized lab-on-chip devices. DEP
      exploits the dielectric properties of particles suspended in a fluid, in a region
      where the amplitude of the electric field is characterized by a high gradient.
      Langerhans islets are aggregates of cells and have a minimum diameter of 50
      microns. Dielectric models of pancreatic islets as cell aggregates were derived
      from single pancreatic beta cells model. Numerical simulations were performed to
      optimize the exact shape and size of the quadrupole microelectrode configuration
      and to determine the DEP forces acting on islets. A custom electronic setup was
      developed for the generation of sinusoidal signals with proper voltage and
      frequency and used to perform DEP experiments with samples of Langerhans islets.
      Dielectric models were found sufficiently accurate and negative DEP, showing
      repulsion from the electrodes, was observed for pancreatic islets. The results of
      this work demonstrate that Langerhans islet can be manipulated without physical
      contact by dielectrophoresis, a technique that can be applied on cell aggregates
      in miniaturized lab-on-chip devices.

PMID- 23161154
TI  - Winter rainfall predicts phenology in widely separated populations of a migrant
      songbird.
AB  - Climate change is affecting behaviour and phenology in many animals. In migratory
      birds, weather patterns both at breeding and at non-breeding sites can influence
      the timing of spring migration and breeding. However, variation in responses to
      weather across a species range has rarely been studied, particularly among
      populations that may winter in different locations. We used prior knowledge of
      migratory connectivity to test the influence of weather from predicted non
      breeding sites on bird phenology in two breeding populations of a long-distance
      migratory bird species separated by 3,000 km. We found that winter rainfall
      showed similar associations with arrival and egg-laying dates in separate
      breeding populations on an east-west axis: greater rainfall in Jamaica and
      eastern Mexico was generally associated with advanced American redstart
      (Setophaga ruticilla) phenology in Ontario and Alberta, respectively. In Ontario,
      these patterns of response could largely be explained by changes in the behaviour
      of individual birds, i.e., phenotypic plasticity. By explicitly incorporating
      migratory connectivity into responses to climate, our data suggest that widely
      separated breeding populations can show independent and geographically specific
      associations with changing weather conditions. The tendency of individuals to
      delay migration and breeding following dry winters could result in population
      declines due to predicted drying trends in tropical areas and the tight linkage
      between early arrival/breeding and reproductive success in long-distance
      migrants.

PMID- 23161155
TI  - Differential effects of duration for ocular and cervical vestibular evoked
      myogenic potentials evoked by air- and bone-conducted stimuli.
AB  - We investigated the changes in cervical (cVEMP) and ocular (oVEMP) vestibular
      evoked myogenic potentials in response to differing stimulus durations. cVEMPs (n
      = 12 subjects) and oVEMPs (n = 13 subjects) were recorded using air-conducted
      (AC: 500 Hz) and bone-conducted (BC: 500 Hz) tone burst stimuli with durations
      varying from 2 to 10 ms. BC stimulation was applied both frontally and to the
      mastoid. AC cVEMPs showed an increase in amplitude with stimuli up to 6-ms
      duration associated with a prolonged latency, as previously reported. In
      contrast, AC oVEMP amplitude decreased with increasing stimulus duration. BC
      stimuli showed no significant increase in amplitude with increasing stimulus
      duration for either reflex using either location of stimulation. BC cVEMPS
      following forehead stimulation showed a significant decrease as duration
      increased, and BC oVEMPs to mastoid stimulation were largest at 2 ms and
      decreased thereafter. We conclude that an increase in amplitude with increasing
      stimulus duration, using 500 Hz stimuli, only occurs for AC cVEMPs. There is no
      definite benefit in using longer stimuli than 2 ms for BC or oVEMP studies.
      Shorter stimuli also minimise subject exposure to sound and vibration.

PMID- 23161156
TI  - Hand use for grasping in a bimanual task: evidence for different roles?
AB  - It has been proposed that the two hands play different roles during bimanual
      object interaction. The right hand takes on an explorative, highly precise,
      manipulative role while the left hand supports and stabilizes the object. Does
      this division of labour influence hand use during visually guided grasping? Three
      experiments were designed to address this question: right-handed individuals put
      together 3D models using big or small building blocks scattered across a
      tabletop. Participants were free to build the models; however, it felt
      comfortable (Experiment 1) or they were required to build on a large (Experiment
      2) or small (Experiment 3) base plate. In Experiment 1, the right hand was
      preferred for grasping while the left hand stabilized the building model. When
      participants used the large base plate (Experiment 2), right hand use for
      grasping decreased and left hand use increased. The plate provided freedom to the
      left hand from having to stabilize the building model, but it also interfered
      with right/left hand movements directed towards the opposite side of the grasping
      hand (contralateral movements). To investigate which of these two factors would
      explain the change in hand use for grasping, a very small base plate was used in
      the last experiment. Results showed similar right hand use values to those seen
      in the first experiment (without the use of a plate), even though the left hand
      was 'released from its stabilizing duties.' The results predict a left-hemisphere
      right hand advantage in the control of grasping.

PMID- 23161157
TI  - Tactile perceptual learning: learning curves and transfer to the contralateral
      finger.
AB  - Tactile perceptual learning has been shown to improve performance on tactile
      tasks, but there is no agreement about the extent of transfer to untrained skin
      locations. The lack of such transfer is often seen as a behavioral index of the
      contribution of early somatosensory brain regions. Moreover, the time course of
      improvements has never been described explicitly. Sixteen subjects were trained
      on the Ludvigh task (a tactile vernier task) on four subsequent days. On the
      fifth day, transfer of learning to the non-trained contralateral hand was tested.
      In five subjects, we explored to what extent training effects were retained
      approximately 1.5 years after the final training session, expecting to find long
      term retention of learning effects after training. Results showed that tactile
      perceptual learning mainly occurred offline, between sessions. Training effects
      did not transfer initially, but became fully available to the untrained
      contralateral hand after a few additional training runs. After 1.5 years,
      training effects were not fully washed out and could be recuperated within a
      single training session. Interpreted in the light of theories of visual
      perceptual learning, these results suggest that tactile perceptual learning is
      not fundamentally different from visual perceptual learning, but might proceed at
      a slower pace due to procedural and task differences, thus explaining the
      apparent divergence in the amount of transfer and long-term retention.

PMID- 23161158
TI  - Deficits of cortical oculomotor mechanisms in cerebellar atrophy patients.
AB  - Commonly, the cerebellum is not associated with cortical components of saccadic
      eye movement programming. The present study investigates cerebellar effects on
      visually guided saccades in reflexive tasks (step, gap, overlap) and on
      internally driven saccades in intentional tasks (anti, memory, short memory
      sequences of four targets) in five patients with isolated cerebellar atrophy. The
      cerebellar dysfunction led to impairments in both reflexive and intentional
      saccades. Cerebellar atrophy patients showed an increase in the gain variability
      and an increase in the saccade latency. Furthermore, in the memory and anti task,
      suppression and pro-saccade errors were more frequent in the atrophy group
      compared to the control group. In the sequence task, patients had difficulties
      reproducing all four target locations in the order of the displayed sequence. The
      high variability of the saccade gain is a common observation in cerebellar
      atrophy patients and can be explained by the general variability present in the
      saccadic system. The increase in the saccade latency could be due to a cerebellar
      contribution to cortical processes related to fixation and target selection
      preceding the initiation of a saccade. Furthermore, the frequent occurrence of
      saccade errors in the memory and anti task suggests a cerebellar involvement in
      frontal inhibition of unwanted reflexive saccades. The impaired reproduction of
      saccade sequences in atrophy patients points to a deficit in short-term memory
      processes. Thus, this study provides further evidence that the cerebellum is
      involved in different cortical mechanisms related to the control of saccadic eye
      movements.

PMID- 23161159
TI  - Role of pattern, regularity, and silent intervals in auditory stream segregation
      based on inter-aural time differences.
AB  - Tone triplets separated by a pause (ABA_) are a popular tone-repetition pattern
      to study auditory stream segregation. Such triplets produce a galloping rhythm
      when integrated, but isochronous rhythms when segregated. Other patterns lacking
      a pause may produce less-prominent rhythmic differences but stronger streaming.
      Here, we evaluated whether this difference is readily explained by the presence
      of the pause and potentially associated with the reduction of adaptation, or
      whether there is contribution of tone pattern per se. Sequences with repetitive
      ABA_ and ABAA patterns were presented in magnetoencephalography. A and B tones
      were separated by differences in inter-aural time differences (DeltaITD). Results
      showed that the stronger streaming of ABAA was associated with a more prominent
      release from the adaptation of the P(1)m in auditory cortex. We further compared
      behavioral streaming responses for patterns with and without pauses, and varied
      the position of the pause and pattern regularity. Results showed a major effect
      of the pauses' presence, but no prominent effects of tone pattern or pattern
      regularity. These results make a case for the existence of an early, primitive
      streaming mechanism that does not require an analysis of the tone pattern at
      later stages suggested by predictive-coding models of auditory streaming. The
      results are better explained by the simpler population-separation model and
      stress the previously observed role of neural adaptation for streaming
      perception.

PMID- 23161160
TI  - Effects of speeding up or slowing down animate or inanimate motions on timing.
AB  - It has recently been suggested that time perception and motor timing are
      influenced by the presence of biological movements and animacy in the visual
      scene. Here, we investigated the interactions among timing, speed and animacy in
      two experiments. In Experiment 1, observers had to press a button in synchrony
      with the landing of a falling ball while a dancer or a whirligig moved in the
      background of the scene. The speed of these two characters was artificially
      changed across sessions. We found striking differences in the timing of button
      press responses as a function of the condition. Responses were delayed
      considerably with increasing speed of the whirligig. By contrast, the effect of
      the dancer's speed was weaker and in the opposite direction. In Experiment 2, we
      assessed the perceived animacy of these characters and found that the dancer was
      rated as much more animate than the whirligig, irrespective of the character
      speed. The results are consistent with the hypothesis that event timers are
      selectively biased as a function of perceived animacy, implicating high-level
      mechanisms for time modulation. However, response timing interacts with perceived
      animacy and speed in a complex manner.

PMID- 23161161
TI  - Analysis of 15 cases of auricular keloids following conchal cartilage grafts in
      an asian population.
AB  - BACKGROUND: Recently, rhinoplasty techniques have advanced significantly and are
      frequently combined with columellar struts using conchal cartilage grafts to
      sufficiently reshape the nasal tip. For this reason, auricular keloids following
      harvesting of conchal cartilage grafts are expected to occur with greater
      frequency. The aim of this study was to share our experiences with auricular
      keloids and to suggest possible risk factors. METHODS: We conducted a
      retrospective review of patients with pathologically confirmed auricular keloids
      that were surgically excised with primary closure after conchal cartilage grafts
      were harvested. Starting between days 21 and 28 postoperatively, patients were
      instructed to use magnets for approximately 12 h a day for 6 months until
      adjuvant pressure therapy was completed. Recurrence after treatment was recorded.
      In all patients, a follow-up period of 18 months was required. RESULTS: Auricular
      keloids were successfully treated in 93.3 % of the cases and 6.7 % of the cases
      had recurrence. The postoperative course was uneventful without exception. There
      was a male predominance of auricular keloids after conchal cartilage graft
      harvesting. In addition, a high growth rate as a result of the short duration of
      the keloid before treatment was seen. CONCLUSIONS: Adjuvant pressure therapy
      using magnets is useful for treating auricular keloids following conchal
      cartilage graft harvesting. In addition, surgeons should be careful when
      performing conchal cartilage harvest to avoid needless injury to the adjacent
      skin flap. LEVEL OF EVIDENCE IV: This journal requires that authors assign a
      level of evidence to each article. For a full description of these Evidence-Based
      Medicine ratings, please refer to the Table of Contents or the online
      Instructions to Authors www.springer.com/00266 .

PMID- 23161153
TI  - Telomere shortening and Alzheimer's disease.
AB  - Telomeres, at the ends of chromosomes and strands of genetic material, become
      shorter as cells divide in the process of aging. Telomere length has been
      considered as a biological marker of age. Telomere length shortening has also
      been evidenced as the causable role in age-related neurodegenerative diseases,
      including Alzheimer's disease (AD). It has been demonstrated that telomere
      shortening has been associated with cognitive impairment, amyloid pathology and
      hyper-phosphorylation of tau in AD and plays an important role in the
      pathogenesis of AD via the mechanism of oxidative stress and inflammation.
      However, it seems that there is no relationship between telomere shortening and
      AD. Therefore, it is essential for further clarification of telomere-related
      pathogenesis in AD.

PMID- 23161162
TI  - Physical characterization and formulation development of a recombinant
      pneumolysoid protein-based pneumococcal vaccine.
AB  - Streptococcus pneumoniae is a major cause of death in children worldwide. There
      are more than 90 known pneumococcus serotypes that vary by geographical location.
      Pneumolysin is a protein toxin produced by virtually all invasive strains of S.
      pneumoniae and is considered an important virulence factor. Pneumolysin is
      immunogenic and has the potential to be a new vaccine antigen offering broad
      serotype-independent coverage. To develop a stable vaccine formulation, the
      conformational stability of a recombinant pneumolysin mutant (pneumolysoid L460D)
      was characterized by various techniques. Three data visualization diagrams were
      constructed to summarize the biophysical data of the L460D pneumolysoid; the
      protein is most stable in solution at pH 6-7, and loses conformational integrity
      above 48 degrees C. Excipient screening assays were performed and sugars such as
      trehalose and sucrose stabilized the pneumolysin mutant with respect to improving
      thermal transition temperatures and minimizing aggregation. In addition, the
      protein antigen showed efficient binding to aluminum hydroxide adjuvant. The
      conformational stability of the L460D pneumolysoid on the surface of alhydrogel
      adjuvant was little affected by adsorption, either with or without excipients.
      These studies provide important preformulation characterization information
      useful for the development of a stable pneumolysin mutant-based vaccine.

PMID- 23161163
TI  - The cerebral cortex of Albert Einstein: a description and preliminary analysis of
      unpublished photographs.
AB  - Upon his death in 1955, Albert Einstein's brain was removed, fixed and
      photographed from multiple angles. It was then sectioned into 240 blocks, and
      histological slides were prepared. At the time, a roadmap was drawn that
      illustrates the location within the brain of each block and its associated
      slides. Here we describe the external gross neuroanatomy of Einstein's entire
      cerebral cortex from 14 recently discovered photographs, most of which were taken
      from unconventional angles. Two of the photographs reveal sulcal patterns of the
      medial surfaces of the hemispheres, and another shows the neuroanatomy of the
      right (exposed) insula. Most of Einstein's sulci are identified, and sulcal
      patterns in various parts of the brain are compared with those of 85 human brains
      that have been described in the literature. To the extent currently possible,
      unusual features of Einstein's brain are tentatively interpreted in light of what
      is known about the evolution of higher cognitive processes in humans. As an aid
      to future investigators, these (and other) features are correlated with blocks on
      the roadmap (and therefore histological slides). Einstein's brain has an
      extraordinary prefrontal cortex, which may have contributed to the neurological
      substrates for some of his remarkable cognitive abilities. The primary
      somatosensory and motor cortices near the regions that typically represent face
      and tongue are greatly expanded in the left hemisphere. Einstein's parietal lobes
      are also unusual and may have provided some of the neurological underpinnings for
      his visuospatial and mathematical skills, as others have hypothesized. Einstein's
      brain has typical frontal and occipital shape asymmetries (petalias) and grossly
      asymmetrical inferior and superior parietal lobules. Contrary to the literature,
      Einstein's brain is not spherical, does not lack parietal opercula and has non
      confluent Sylvian and inferior postcentral sulci.

PMID- 23161164
TI  - Linking the development of ventilator-induced injury to mechanical function in
      the lung.
AB  - Management of ALI/ARDS involves supportive ventilation at low tidal volumes (V t)
      to minimize the rate at which ventilator induced lung injury (VILI) develops
      while the lungs heal. However, we currently have few details to guide the
      minimization of VILI in the ALI/ARDS patient. The goal of the present study was
      to determine how VILI progresses with time as a function of the manner in which
      the lung is ventilated in mice. We found that the progression of VILI caused by
      over-ventilating the lung at a positive end-expiratory pressure of zero is
      accompanied by progressive increases in lung stiffness as well as the rate at
      which the lung derecruits over time. We were able to accurately recapitulate
      these findings in a computational model that attributes changes in the dynamics
      of recruitment and derecruitment to two populations of lung units. One population
      closes over a time scale of minutes following a recruitment maneuver and the
      second closes in a matter of seconds or less, with the relative sizes of the two
      populations changing as VILI develops. This computational model serves as a basis
      from which to link the progression of VILI to changes in lung mechanical
      function.

PMID- 23161165
TI  - Quantification of biomechanical interaction of transcatheter aortic valve stent
      deployed in porcine and ovine hearts.
AB  - Success of the deployment and function in transcatheter aortic valve replacement
      is heavily reliant on the tissue-stent interaction. The present study quantified
      important tissue-stent contact variables of self-expanding transcatheter aortic
      valve stents when deployed into ovine and porcine aortic roots, such as the stent
      radial expansion force, stent pullout force, the annulus deformation response and
      the coefficient of friction on the tissue-stent contact interface. Braided
      Nitinol stents were developed, tested to determine stent crimped diameter vs.
      stent radial force from a stent crimp experiment, and deployed in vitro to
      quantify stent pullout, aortic annulus deformation, and the coefficient of
      friction between the stent and the aortic tissue from an aortic root-stent
      interaction experiment. The results indicated that when crimped at body
      temperature from 26 mm to 19, 21 and 23 mm stent radial forces were approximately
      30-40% higher than those crimped at room temperature. Coefficients of friction
      leveled to approximately 0.10 +/- 0.01 as stent wire diameter increased and
      annulus size decreased from 23 to 19 mm. Regardless of aortic annulus size and
      species tested, it appeared that a minimum of about 2.5 mm in annular dilatation,
      caused by about 60 N of radial force from stent expansion, was needed to anchor
      the stent against a pullout into the left ventricle. The study of the contact
      biomechanics in animal aortic tissues may help us better understand
      characteristics of tissue-stent interactions and quantify the baseline responses
      of non-calcified aortic tissues.

PMID- 23161166
TI  - Accelerometry reveals differences in gait variability between patients with
      multiple sclerosis and healthy controls.
AB  - Variability of movement reflects important information for the maintenance of the
      health of the system. For pathological populations, changes in variability during
      gait signal the presence of abnormal motor control strategies. For persons with
      multiple sclerosis (PwMS), extensive gait problems have been reported including
      changes in gait variability. While previous studies have focused on footfall
      variability, the present study used accelerometers on the trunk to measure
      variability during walking. Thus, the purpose of this study was to examine the
      variability of the acceleration pattern of the upper and lower trunk in PwMS
      compared to healthy controls. We extracted linear and nonlinear measures of gait
      variability from 30 s of steady state walking for 15 PwMS and 15 age-matched
      healthy controls. PwMS had altered variability compared to controls with greater
      Lyapunov exponent in the ML (p < 0.001) and AP (p < 0.001) directions, and
      greater frequency dispersion in the ML direction (p = 0.034). PwMS also
      demonstrated greater mean velocity in the ML direction (p = 0.045) and lower root
      mean square of acceleration in the AP direction (p = 0.040). These findings
      indicate that PwMS have altered structure of variability of the trunk during gait
      compared to healthy controls and agree with previous findings related to changes
      in gait variability in PwMS.

PMID- 23161167
TI  - Hyaluronic acid-dependent protection against alkali-burned human corneal cells.
AB  - Hyaluronic acid (HA) is a high-molecular-weight glycosaminoglycan and
      extracellular matrix component that promotes cell proliferation. This study aimed
      to evaluate the effects of HA on alkali-injured human corneal epithelial cells in
      vitro, and to elucidate the mechanisms by which HA mediates corneal cell
      protection. A human corneal epithelial cell line (HCE-2) was treated with sodium
      hydroxide before incubation with low-molecular-weight HA (LMW-HA, 127 kDa) or
      high-molecular-weight HA (HMW-HA, 1525 kDa). A global proteomic analysis was then
      performed. Our data indicated that HA treatment protects corneal epithelial cells
      from alkali injury, and that the molecular weight of HA is a crucial factor in
      determining its effects. Only HMW-HA reduced NaOH-induced cytotoxic effects in
      corneal cells significantly and increased their migratory and wound healing
      ability. Results from 2D-DIGE and MALDI-TOF/TOF MS analyses indicated that HMW-HA
      modulates biosynthetic pathways, cell migration, cell outgrowth, and protein
      degradation to stimulate wound healing and prevent cell death. To our knowledge,
      our study is the first to report the possible mechanisms by which HMW-HA promotes
      repair in alkali-injured human corneal epithelial cells.

PMID- 23161168
TI  - Neuroproteomic profiling of human brain tissue using multidimensional separation
      techniques and selective enrichment of membrane proteins.
AB  - Hydrophobic membrane proteins (MPs) occupy a unique niche in the brain proteome
      research due to their important physiological roles. Therefore, the extraction,
      separation, and identification of MPs are of great interest in proteomic
      analysis. We applied various proteomic techniques to enrich, separate, and
      analyze the human brain proteome, including membrane proteome. Temperature
      induced phase fractionation with the nonionic surfactant Triton X-114 was used to
      simultaneously extract, separate, and concentrate low abundant hydrophobic and
      high abundant hydrophilic proteins from human brain tissue. The extracted and
      delipidated proteins were analyzed by two-dimensional gel electrophoresis (2DE).
      Approximately 600 spots were detected in the gels. In-solution digestion was
      performed on 3 kDa spin filters. Tryptic peptides were separated using RP nano-LC
      and analyzed using two different high performance mass spectrometers, linear ion
      trap-Fourier transform and a linear ion trap-Orbitrap to reveal the low abundant
      MPs. In total, 837 and 780 unique proteins were identified by using linear ion
      trap-Fourier transform and linear ion trap-Orbitrap mass spectrometers,
      respectively. More than 29% of the identified proteins were classified as MPs
      with significant biological functions such as ion channels and transporters. Our
      study establishes a simple and rapid shotgun approach for the characterization of
      the brain proteome, and allows comprehensive analysis of brain membrane
      proteomes.

PMID- 23161169
TI  - Warning navigation system using real-time safe region monitoring for otologic
      surgery.
AB  - PURPOSE: We developed a surgical navigation system that warns the surgeon with
      auditory and visual feedback to protect the facial nerve with real-time
      monitoring of the safe region during drilling. METHODS: Warning navigation
      modules were developed and integrated into a free open source software platform.
      To obtain high registration accuracy, we used a high-precision laser-sintered
      template of the patient's bone surface to register the computed tomography (CT)
      images. We calculated the closest distance between the drill tip and the surface
      of the facial nerve during drilling. When the drill tip entered the safe regions,
      the navigation system provided an auditory and visual signal which differed in
      each safe region. To evaluate the effectiveness of the system, we performed
      phantom experiments for maintaining a given safe margin from the facial nerve
      when drilling bone models, with and without the navigation system. The error of
      the safe margin was measured on postoperative CT images. In real surgery, we
      evaluated the feasibility of the system in comparison with conventional facial
      nerve monitoring. RESULTS: The navigation accuracy was submillimeter for the
      target registration error. In the phantom study, the task with navigation
      ([Formula: see text] mm) was more successful with smaller error, than the task
      without navigation ([Formula: see text] mm, [Formula: see text]). The clinical
      feasibility of the system was confirmed in three real surgeries. CONCLUSIONS:
      This system could assist surgeons in preserving the facial nerve and potentially
      contribute to enhanced patient safety in the surgery.

PMID- 23161170
TI  - Retinol binding protein-albumin domain III fusion protein deactivates hepatic
      stellate cells.
AB  - Liver fibrosis is characterized by accumulation of extracellular matrix, and
      activated hepatic stellate cells (HSCs) are the primary source of the fibrotic
      neomatrix and considered as therapeutic target cells. We previously showed that
      albumin in pancreatic stellate cells (PSCs), the key cell type for pancreatic
      fibrogenesis, is directly involved in the formation of vitamin A-containing lipid
      droplets, inhibiting PSC activation. In this study, we evaluated the anti
      fibrotic activity of both albumin and retinol binding protein-albumin domain III
      fusion protein (R-III), designed for stellate cell-targeted delivery of albumin
      III, in rat primary HSCs and investigated the underlying mechanism. Forced
      expression of albumin or R-III in HSCs after passage 2 (activated HSCs) induced
      lipid droplet formation and deactivated HSCs, whereas point mutations in high
      affinity fatty acid binding sites of albumin domain III abolished their
      activities. Exogenous R-III, but not albumin, was successfully internalized into
      and deactivated HSC-P2. When HSCs at day 3 after plating (pre-activated HSCs)
      were cultured in the presence of purified R-III, spontaneous activation of HSCs
      was inhibited even after passage 2, suggestive of a potential for preventive
      effect. Furthermore, treatment of HSCs-P2 with R-III led to a significant
      reduction in both cytoplasmic levels of all-trans retinoic acid and the
      subsequent retinoic acid signaling. Therefore, our data suggest that albumin
      deactivates HSCs with reduced retinoic acid levels and that R-III may have
      therapeutic and preventive potentials on liver fibrosis.

PMID- 23161171
TI  - Quadruple 9-mer-based protein binding microarray analysis confirms AACnG as the
      consensus nucleotide sequence sufficient for the specific binding of AtMYB44.
AB  - AtMYB44 is a member of the R2R3 MYB subgroup 22 transcription factors and
      regulates diverse cellular responses in Arabidopsis thaliana. We performed
      quadruple 9-merbased protein binding microarray (PBM) analysis, which revealed
      that full-size AtMYB44 recognized and bound to the consensus sequence AACnG,
      where n represents A, G, C or T. The consensus sequence was confirmed by
      electrophoretic mobility shift assay (EMSA) with a truncated AtMYB44 protein
      containing the N-terminal side R2R3 domain. This result indicates that the R2R3
      domain alone is sufficient to exhibit AtMYB44 binding specificity. The sequence
      AACnG is the type I binding site for MYB transcription factors, including all
      members of the subgroup 22. EMSA showed that the R2R3 domain protein binds in
      vitro to promoters of randomly selected Arabidopsis genes that contain the
      consensus binding sequence. This implies that AtMYB44 binds to any promoter
      region that contains the consensus sequence, without determining their functional
      activity or specificity. The C-terminal side transcriptional activation domain of
      AtMYB44 contains an asparagine-rich fragment, NINNTTSSRHNHNN (aa 215-228), which,
      among the members of subgroup 22, is unique to AtMYB44. A transcriptional
      activation assay in yeast showed that this fragment is included in a region (aa
      200-240) critical for the ability of AtMYB44 to function as a transcriptional
      activator. We hypothesize that the C-terminal side of the protein, but not the N
      terminal side of the R2R3 domain, contributes to the functional activity and
      specificity of AtMYB44 through interactions with other regulators generated by
      each of a variety of stimuli.

PMID- 23161172
TI  - Olfactomedin 4 suppresses tumor growth and metastasis of mouse melanoma cells
      through downregulation of integrin and MMP genes.
AB  - Olfactomedin 4 (OLFM4) is highly expressed in gastrointestinal cancers and has an
      anti-apoptotic function. The roles of OLFM4 in tumor growth and metastasis and
      how it functions in these processes remain elusive. We investigated the function
      of OLFM4 in tumor growth and metastasis using B16F10 mouse melanoma cells as an
      experimental system. Our results showed that OLFM4 had no positive effect on cell
      viability or cell cycle progression in B16F10 cells. However, it significantly
      suppressed the tumorigenicity of B16F10 cells, i.e., intradermal primary tumor
      growth and lung metastasis. OLFM4 also suppressed the migration and invasion of
      B16F10 cells in vitro. For further insight into the mechanisms underlying OLFM4
      mediated suppression of tumor progression, we examined the effect of OLFM4 on the
      expression of integrin and matrix metalloproteinase (MMP), both of which are
      involved in tumor progression. Overexpression of OLFM4 clearly reduced the
      expression levels of integrin alpha1, integrin alpha4, integrin alpha5, integrin
      alpha6, and MMP9. Moreover, forced expression of MMP9 attenuated the inhibitory
      activity of OLFM4 on migration and invasiveness. Our findings provide the
      experimental evidence that OLFM4 may function as a tumor suppressor and an anti
      metastatic gene during tumor progression.

PMID- 23161173
TI  - Gintonin, a ginseng-derived novel ingredient, evokes long-term potentiation
      through N-methyl-D-aspartic acid receptor activation: involvement of LPA
      receptors.
AB  - Ginseng has been shown to have memory-improving effects in human. However, little
      is known about the active components and the molecular mechanisms underlying its
      effects. Recently, we isolated novel lysophosphatidic acids (LPAs)-ginseng
      protein complex derived from ginseng, gintonin. Gintonin activates G protein
      coupled LPA receptors with high affinity. Gintonin activated Ca2+-activated
      Clchannels in Xenopus oocytes through the activation of endogenous LPA receptor.
      In the present study, we investigated whether the activation of LPA receptor by
      gintonin is coupled to the regulation of N-methyl-D-aspartic acid (NMDA) receptor
      channel activity in Xenopus oocytes expressing rat NMDA receptors. The NMDA
      receptor-mediated ion current (I ( NMDA )) was measured using the two-electrode
      voltage-clamp technique. In oocytes injected with cRNAs encoding NMDA receptor
      subunits, gintonin enhanced I ( NMDA ) in a concentration-dependent manner.
      Gintonin-mediated I ( NMDA ) enhancement was blocked by Ki16425, an LPA1/3
      receptor antagonist. Gintonin action was blocked by a PLC inhibitor, IP3 receptor
      antagonist, Ca2+ chelator, and a tyrosine kinase inhibitor. The site-directed
      mutation of Ser1308 of the NMDA receptor, which is phosphorylated by protein
      kinase C (PKC), to an Ala residue, or co-expression of receptor protein tyrosine
      phosphatase with the NMDA receptor attenuated gintonin action. Moreover, gintonin
      treatment elicited a transient elevation of [Ca2+](i) in cultured hippocampal
      neurons and elevated longterm potentiation (LTP) in both concentration-dependent
      manners in rat hippocampal slices. Gintonin-mediated LTP induction was abolished
      by Ki16425. These results indicate that gintonin-mediated I ( NMDA ) potentiation
      and LTP induction in the hippocampus via the activation of LPA receptor might be
      responsible for ginseng-mediated improvement of memory-related brain functions.

PMID- 23161174
TI  - Bioinformatics aggregation predictors in the study of protein conformational
      diseases of the human nervous system.
AB  - Conformational protein diseases of the human central nervous system represent a
      subject that has crucial theoretical and medical implications. They include
      several important neurodegenerative diseases, such as Alzheimer's, Parkinson's,
      Huntington's and Creutzfeldt-Jacob's diseases, amyotrophic lateral sclerosis, and
      the tauopathies. They occur when soluble proteins undergo conformational
      rearrangements becoming capable of aggregate into beta-sheets conformations
      leading to the production of insoluble complexes known as amyloid deposits, that
      accumulate and lead to neurons and glial cells death. Theoretical and
      experimental evidence indicates that a key role in the conformational changes
      leading to amyloid formation is played by short sequence stretches within a given
      protein. Thus, the identification of protein regions potentially involved in
      aggregate formation and the characterization of their properties are relevant
      questions in the study of conformational proteins diseases. To address these
      questions, bioinformatics methods might provide an important contribution,
      suggesting possible mechanisms of protein aggregation, and focusing and orienting
      the experimental work. Thus, in the first part of the present review
      bioinformatics methods specifically attempting to predict aggregation-prone
      regions in proteins will be briefly described. Furthermore, the results provided
      by the combined use of some of them to analyze a set of particularly important
      proteins involved in human degenerative diseases will be discussed.

PMID- 23161175
TI  - The expression of serotonin transporter protein correlates with the severity of
      psoriasis and chronic stress.
AB  - Psoriasis may be worsened by stress and mood disorders. There is an increased
      expression of the serotonin transporter protein (SERT) in involved psoriatic skin
      as compared to non-involved psoriatic skin and normal skin. The aim of this study
      was to investigate if the increased expression of SERT in psoriasis correlates
      with the severity of disease, chronic stress, and depression. Biopsies from
      involved and non-involved skin from the back of 20 patients with chronic plaque
      psoriasis were immunohistochemically analysed, using a monoclonal antibody to
      SERT. The severity of psoriasis was assessed for each patient using the Psoriasis
      area and severity index (PASI). Levels of depression and chronic stress were
      measured using Beck's Depression Inventory (BDI) and the salivary cortisol test,
      respectively. A positive correlation (r = 0.53; p < 0.05) between PASI and the
      numbers of SERT-positive dendritic cells in the epidermis of involved psoriatic
      skin was determined. We also observed a negative correlation (r = -0.46; p <
      0.05) between salivary cortisol ratio levels and the numbers of SERT-positive
      cells in the epidermis of involved psoriatic skin, indicating a correlation
      between SERT expression and chronic stress. The serotonergic system may be
      involved in the chronic inflammation evident in psoriatic skin. Through
      modulating the levels of SERT, there might be a therapeutic possibility for
      reducing chronic inflammation in psoriasis.

PMID- 23161176
TI  - Contemporary sample stacking in analytical electrophoresis.
AB  - Sample stacking is a term denoting a multifarious class of methods and their
      names that are used daily in CE for online concentration of diluted samples to
      enhance separation efficiency and sensitivity of analyses. The essence of these
      methods is that analytes present at low concentrations in a large injected sample
      zone are concentrated into a short and sharp zone (stack) in the separation
      capillary. Then the stacked analytes are separated and detected. Regardless of
      the diversity of the stacking electromigration methods, one can distinguish four
      main principles that form the bases of nearly all of them: (i) Kohlrausch
      adjustment of concentrations, (ii) pH step, (iii) micellar methods, and (iv)
      transient ITP. This contribution is a continuation of our previous reviews on the
      topic and brings an overview of papers published during 2010-2012 and relevant to
      the mentioned principles (except the last one which is covered by another review
      in this issue).

PMID- 23161177
TI  - Effect of topical pressure-lowering medication on prevention of intraocular
      pressure spikes after intravitreal injection.
AB  - Purpose. The aim of this study was to evaluate pressure increases after
      intravitreal injections (IVI) and the interest in using prophylactic pressure
      lowering medications. ?Methods. This was a prospective study of 250 anti-vascular
      endothelial growth factor IVI (ranibizumab) divided into 5 groups of 50 IVI
      (group 1: no intraocular pressure [IOP]-lowering medication; group 2:
      apraclonidine 1%; group 3: acetazolamide; group 4: fixed association brimonidine
      + timolol; group 5: fixed association dorzolamide + timolol). The IOP was
      measured before, immediately after (T1), 15 minutes after (T15), and 45 minutes
      after (T45) the IVI using a tonometer. The data were analyzed by analysis of
      variance followed by a Bonferroni as post hoc test if necessary.?Results. The
      mean IOP peak in group 1 was 46.4+/-10 mmHg at T1, 21.7+/-10.2 mmHg at T15, and
      15.4+/-8.6 mmHg at T45. It was not correlated with axial length (r=0.04, p=0.81)
      or lens status (phakic vs pseudophakic: p=0.88). A mild but significant
      correlation was found with age (r=0.36, p=0.006). Topical medications produced a
      significant reduction of IOP at every time point, of around 9 mmHg at T1. The
      reduction in IOP obtained with acetazolamide was not significant at T1 (-1.6
      mmHg, p=0.12), but became significant at T15 and T45 (p=0.011 and p=0.015).
      ?Conclusions. Intraocular pressure spike was high but transient. Topical
      medications, however, produced a significant reduction in IOP spike as well as in
      the duration of the increased pressure. It would be advisable to prevent this IOP
      spike, especially when procedures are repeated, notably in patients with
      glaucoma.

PMID- 23161178
TI  - BOLD responses to different temporospatial frequency stimuli in V1 and V2 visual
      cortex of anisometropic amblyopia.
AB  - PURPOSE: Functional magnetic resonance imaging (fMRI) is the most advanced
      neuroimaging technique. The aim of this study was to investigate the blood
      oxygenation level-dependent (BOLD) of V1 and V2 visual cortex in anisometropic
      amblyopia with fMRI and explore the neural mechanism of amblyopia. METHODS: fMRI
      was performed with a 3.0-T MRI scanner during reversal checkerboard visual
      stimulation with different spatial frequencies (SF) of 0.4, 2, and 8 cpd in 2
      states of temporal frequencies (TF) of 6 Hz and 8 Hz in a group of patients with
      anisometropic amblyopia (n=5) and a group of normal observers (n=4). Data were
      processed by SPM software offline. Responses of different eyes were compared in
      different conditions. RESULTS: The BOLD signal magnitude in V1 and V2 visual
      cortex of amblyopic eyes was significantly lower than the fellow eyes with
      anisometropic amblyopia at low SF (0.4-2 cpd) (p<0.05), but it was significantly
      higher than the fellow eyes at high SF (8 cpd) (p<0.05). The BOLD signal
      magnitude in V1 and V2 visual cortex of amblyopic eyes was significantly lower
      than the nondominant eyes in normal subjects in all conditions (p<0.001).
      CONCLUSIONS: There are cortical deficits in V1 and V2 visual cortex of
      anisometropic amblyopia, which may be useful for selecting an optimum stimulus at
      proper temporospatial frequency.

PMID- 23161179
TI  - Role of interleukin 6-174G>C polymorphism ?in primary open-angle glaucoma.
AB  - PURPOSE: In addition to its proinflammatory effects, interleukin (IL)-6 also
      possesses antiapoptotic properties. Recently, IL-6 has been reported to protect
      retinal ganglion cells from pressure-induced apoptosis, indicating a possible
      role in the pathogenesis of primary open-angle glaucoma (POAG). A common
      polymorphism in the promoter region of IL-6 gene at position -174 characterized
      by a substitution from G to C has been found to decrease transcription rate of IL
      6. The aim of our study was to investigate a hypothesized association between IL
      6-174G>C polymorphism and POAG in Caucasian patients. METHODS. The present case
      control study comprised 191 unrelated patients with POAG and 191 control
      subjects, matched for age and sex. Genotyping of the IL-6-174G>C polymorphism was
      done using polymerase chain reaction. RESULTS: Allelic frequencies and genotype
      distribution of IL-6-174G>C did not significantly differ between patients with
      POAG and control subjects (p>0.05). Presence of the IL-6-174C allele was
      associated with a nonsignificant odds ratio of 0.78 (95% confidence interval 0.46
      1.32; p=0.78) for POAG. CONCLUSIONS: Our findings suggest that the functional IL
      6-174G>C polymorphism itself is unlikely a major risk factor for POAG.

PMID- 23161180
TI  - Scleral buckling dislocation mimicking glaucoma progression.
AB  - PURPOSE. To report a case of scleral dislocation mimicking glaucoma progression.
      METHODS: Interventional case report. RESULTS: A 71-year-old man was referred for
      glaucoma surgery in his right eye because of perimetry defect progression and
      uncontrolled intraocular pressure despite maximal medical therapy. A scleral
      buckling procedure in his right eye was previously performed for rhegmatogenous
      retinal detachment. At the time of presentation, a visible protruded sponge
      buckle element was noted at ocular inspection, without any sign of infection. The
      buckle element was posteriorly in contact with the optic nerve and anteriorly
      protruding under intact conjunctiva. We eventually managed for its removal via
      upper eyelid orbitotomy. Visual field lesions were unchanged on every follow-up
      visit. CONCLUSIONS: This case report describes severe permanent optic nerve
      damage due to previous misdiagnosis of a rare complication of scleral buckling
      surgery. Our surgical solution appears to be a safe and successful approach for
      this ocular disorder, also able to stabilize visual function and interrupt
      disease progression.

PMID- 23161181
TI  - Combined scraping, coagulation, and subconjunctival bevacizumab in Descemet
      stripping automated endothelial keratoplasty for bullous keratopathy.
AB  - PURPOSE: This study evaluated the clinical outcomes of a combined method of
      scraping corneal epithelium, coagulating vessels, and subconjunctival bevacizumab
      in Descemet stripping automated endothelial keratoplasty (DSAEK) for bullous
      keratopathy with corneal neovascularization (NV).? METHODS: The study included
      patients with bullous keratopathy undergoing DSAEK. Indications for DSAEK were
      advanced pseudophakic bullous keratopathy with superficial and deep corneal
      vascularization and failed corneal grafts. Patients were treated by scraping the
      corneal epithelium and lightly coagulating the corneal superficial stromal NV and
      the feeding vessels in the sclera, with a subconjunctival bevacizumab injection
      at the end of surgery. Subconjunctival and perilimbal bevacizumab dose of 2.5
      mg/0.1 mL/affected quadrant was injected at the site of NV in each patient at the
      end of surgery. One or 2 injections were applied. At each visit, a full eye
      examination with photographic documentation was performed. Mean follow-up period
      was 32 (24-36) months.? RESULTS: Eight eyes of 8 patients with high-risk corneal
      transplantation and corneal NV were included in this noncomparative
      interventional case series. The original corneal NV disappeared in all patients
      immediately after surgery. No patient in the series had recurrent corneal NV or
      rejection during at least 24 months of follow-up. ? CONCLUSIONS: . The
      combination of scraping, coagulating, and bevacizumab injection in DSAEK is an
      effective method to treat corneal NV in corneal transplantation for bullous
      keratopathy.

PMID- 23161182
TI  - Ocular pulse amplitude in patients with thyroid-associated ophthalmopathy.
AB  - PURPOSE: To determine ocular pulse volume values in patients with thyroid
      associated ophthalmopathy with normal intraocular pressure, and to test the
      hypothesis that changes in orbital tissue that accompany thyroid-associated
      ophthalmopathy can in turn give changes in choroidal perfusion.? METHODS: In a
      prospective study, we evaluated 30 eyes of 30 consecutive patients with TAO, and
      30 eyes of 30 healthy subjects. Complete ophthalmologic examination including
      dynamic contour tonometry was done. Possible differences in ocular parameters
      between the tested groups were assessed.? RESULTS: . No significant difference
      was found in ocular pulse volume values between the tested subjects (paired test
      p=0.23).? CONCLUSIONS: . The orbit tissue changes that are involved in thyroid
      associated ophthalmopathy do not have much implication on choroidal perfusion, at
      least when intraocular pressure values remain within the normal range.

PMID- 23161183
TI  - Podoplanin expressing cancer associated fibroblasts are associated with
      unfavourable prognosis in adenocarcinoma of the esophagus.
AB  - Overexpression of the mucin-type sialoglycoprotein podoplanin in cancer
      associated fibroblasts (CAFs) was recently shown to be associated with tumor
      progression, metastasis and poor prognosis in lung and breast cancer. Here we
      investigate the role of podoplanin expressing CAFs in esophagal adenocarcinoma
      (AC), its precursor lesions and metastases. Podoplanin expression was
      investigated immunohistochemically in 200 formalin-fixed, paraffin embedded
      specimens of invasive esophagal ACs, their corresponding metastases and 35
      precursor lesions. Podoplanin expressing CAFs (CAF+) were observed in 22 % of
      patients with invasive AC, but not in precursor lesions. CAF+ correlated with
      tumor stage (p = 0.004), lymphovascular tumor invasion (p = 0.018) and lymph node
      metastasis (p = 0.0016). Patients with CAF+ had a significant shorter disease
      free and overall survival (p < 0.05, Cox regression). Podoplanin expressing CAFs
      were only rarely observed in lymph node and distant metastases, as well as in
      local recurrences of ACs. Podoplanin expression in AC tumor cells was seen in
      only four cases. In around 20 % of patients with esophagal AC, podoplanin
      expressing CAFs are evident, defining a high risk subgroup. In these patients,
      podoplanin expressing CAFs might represent new therapeutical targets.

PMID- 23161184
TI  - Metabolite control of angiogenesis: angiogenic effect of citrate.
AB  - Endothelial cells respond to hypoxic changes with resultant accumulation of
      several metabolites and switch over to angiogenic phenotype. Although certain
      intermediates of glycolytic and oxidative metabolic pathways have been known to
      affect angiogenesis, the effect of citrate, which accumulates in certain tumors,
      on angiogenesis is not known. Therefore, the effect of citrate on angiogenesis
      was studied using different model systems. Increased vascularization in
      chorioallantoic membrane assay, increased endothelial sprouting in rat aortic
      rings, and increased expression of CD31, E-selectin in endothelial cells
      suggested a possible proangiogenic effect of citrate. Upregulation of angiogenic
      factors such as vascular endothelial growth factor and fibroblast growth factor
      suggested that the effect of citrate involves modulation of expression of
      angiogenic growth factors. LY 294002, an inhibitor of PI3K-Akt pathway, and
      wortmannin, an inhibitor of Akt pathway, reversed the effect of citrate in human
      umbilical vein endothelial cells. Citrate induced significant upregulation and
      activation of Akt in endothelial cells. Rapamycin, an inhibitor of mTOR, also
      reversed the effect of citrate in human umbilical vein endothelial cells and
      sprouting of aortic rings suggesting that the angiogenic effect of citrate
      involves activation of PI3K-Akt-mTOR pathway. 

PMID- 23161185
TI  - Assessment of ABCD2 scale in patients with transient ischaemic attack or stroke.
AB  - BACKGROUND AND PURPOSE: Stroke risk prediction scores have been designed to
      stratify risk of recurrent cerebrovascular events in patients with transient
      ischaemic attack (TIA) or minor ischaemic stroke (MIS). MATERIAL AND METHODS:
      Consecutive patients with TIA or MIS referring to Ghaem Hospital, Mashhad
      presenting within 24 hours from the onset of symptoms were recruited to the
      prospective cohort study between 2010 and 2011. MIS was defined as an ischaemic
      stroke with National Institutes of Health Stroke Scale (NIHSS) score < 4. The end
      point of the study was a new ischaemic cerebrovascular event or vascular death at
      90 days and, additionally, at 3 days after the index TIA or MIS. The decision to
      admit and of method of treatment in each case was left to the discretion of the
      stroke neurologist. The predictive accuracy of the ABCD2 scoring system for
      recurrent stroke or TIA was quantified by the area under the curve (AUC), using
      the c-statistics. RESULTS: The study included 393 patients with TIA (238 males,
      155 females) and 118 patients with MIS (77 males, 41 females). Among 511 patients
      with minor ischaemic events, 117 strokes (23.2%), 99 TIAs (19.6%), and 11
      vascular deaths (2.2%) occurred within 3 months after the index event. The ABCD2
      score had a weak predictive value for 3-month and 3-day recurrent stroke in
      patients with TIA (AUC = 0.599 and 0.591, respectively), but a high predictive
      value for 3-month and 3-day recurrent stroke in patients with MIS (AUC = 0.727
      and 0.728, respectively). CONCLUSION: The ABCD2 score is highly predictive for
      short-term recurrent stroke in patients with MIS but not in patients with TIA,
      although it was originally designed for patients with TIA.

PMID- 23161186
TI  - Motor cortex stimulation in the treatment of neuropathic pain.
AB  - BACKGROUND AND PURPOSE: Despite the rapid development of neuropharmacotherapy,
      medical treatment of neuropathic pain (NP) still constitutes a significant
      socioeconomic problem. The authors herein present a group of patients treated
      with motor cortex stimulation (MCS) for NP of various types and aetiologies.
      MATERIAL AND METHODS: Our cohort included 12 female and 11 male NP patients aged
      53 +/- 16 treated with MCS. Eleven patients were diagnosed with neuropathic
      facial pain (NFP), 8 with hemi-body neuropathic pain (HNP), and 4 with
      deafferentation pain (DP). Prior to surgery, 16 out of 23 patients were treated
      with repetitive transcranial magnetic stimulation (rTMS), with a positive
      response in 10 cases. Pain intensity in our group was evaluated with the visual
      analogue scale (VAS) one month before and three months after MCS implantation.
      RESULTS: Improvement on the VAS was reported in the whole group of patients (p <
      0.001). The best results were reported in the NFP group (p < 0.001) while the
      worst ones were noted in the DP group (p = 0.04). Anamnesis duration positively
      correlated with outcome. Infection forced the authors to permanently remove the
      system in one case. There were no other complications in the group. CONCLUSIONS:
      Minimally invasive, safe neuromodulative treatment with MCS permits neuropathic
      pain control with good efficacy. The type of neuropathic pain might be a
      prognostic factor.

PMID- 23161187
TI  - Does magnetic resonance spectroscopy identify patients with minimal hepatic
      encephalopathy?
AB  - BACKGROUND AND PURPOSE: The results of a few studies suggest that magnetic
      resonance spectroscopy of the brain could allow detection of minimal hepatic
      encephalopathy. The goal of this study was to assess the ability of magnetic
      resonance spectroscopy to differentiate between cirrhotic patients with and
      without minimal hepatic encephalopathy. MATERIAL AND METHODS: Localized magnetic
      resonance spectroscopy was performed in the basal ganglia, occipital gray matter
      and frontal white matter in 46 patients with liver cirrhosis without overt
      encephalopathy and in 45 controls. Neurological and neuropsychological
      examination was performed in each participant. RESULTS: The patients with liver
      cirrhosis had a decreased ratio of myoinositol to creatine in occipital gray
      matter and frontal white matter (mean: 0.17 +/- 0.05 vs. 0.20 +/- 0.04, p = 0.01
      and 0.15 +/- 0.05 vs. 0.19 +/- 0.04, p < 0.01, respectively) and a decreased
      ratio of choline to creatine in occipital gray matter (mean: 0.32 +/- 0.07 vs.
      0.36 +/- 0.08, p = 0.03). Minimal hepatic encephalopathy was diagnosed in 7
      patients. Metabolite ratios did not differ significantly between patients with
      and without minimal hepatic encephalopathy. Metabolite ratios did not differ
      significantly between patients with Child-Pugh A and those with Child-Pugh B.
      CONCLUSIONS: Magnetic resonance spectroscopy does not allow accurate diagnosis of
      minimal hepatic encephalopathy. A similar profile of metabolites in the brain is
      observed in cirrhotic patients without cognitive impairment.

PMID- 23161188
TI  - Frequency of the C677T variant of the methylenetetrahydrofolate reductase (MTHFR)
      gene in patients with migraine with or without aura - a preliminary report.
AB  - BACKGROUND AND PURPOSE: The aim of our study was to evaluate the frequency of the
      C677T variant in the methylenetetrahydrofolate reductase (MTHFR) gene in patients
      with migraine with or without aura and to find an association between this
      variant and vascular lesions in magnetic resonance imaging of the head, presence
      of patent foramen ovale (PFO) and increased level of homocysteine. MATERIAL AND
      METHODS: Ninety-one patients with migraine, aged 19-57, were investigated in this
      study. The MTHFR C677T variant was genotyped in this group and levels of
      homocysteine, folic acid and vitamin B12 were measured. Transcranial Doppler
      sonography with test for PFO detection by injection of air contrast during the
      Valsalva manoeuvre was performed in each patient. RESULTS: Frequency of the C677T
      variant in the MTHFR gene was similar in patients and controls.
      Hyperhomocysteinaemia was significantly more frequent in migraine patients with
      the C677T variant. The prevalence of PFO was significantly higher in migraine
      patients with aura and the homozygous variant of the MTHFR gene. CONCLUSIONS:
      Frequency of the C677T variant in the MTHFR gene was similar in patients and
      controls. Significantly more frequent prevalence of PFO in migraine patients with
      aura (with homozygous recessive genotype of MTHFR probably suggests their common
      genetic basis. Hyperhomocysteinaemia was significantly more frequent in migraine
      patients with the C677T variant, which could be an additional risk factor of this
      disease.

PMID- 23161189
TI  - Serum S100B protein: a useful marker in obstructive sleep apnea syndrome.
AB  - BACKGROUND AND PURPOSE: We aimed to underline the importance of serum S100B
      protein as a useful biochemical marker in patients with obstructive sleep apnea
      syndrome (OSAS). MATERIAL AND METHODS: Forty-three newly diagnosed patients with
      OSAS (median apnea-hypopnea index [AHI, events/ hour]: 37.5 [range 11.3-137]) and
      25 subjects with AHI < 5 (median AHI: 4.4 [range 0.7-4.8]) were included in the
      study. Serum S100B protein level was tested in serum samples taken after
      polysomnography in both groups and the difference between OSAS patients and the
      control group regarding that level was assessed. In addition, the association of
      S100B protein serum level with age, body mass index, AHI, mean O2 saturation
      percentage during sleep, minimum O2 saturation value (%) at the end of the
      apneas, and the time spent at an O2 saturation less than 90% were analyzed in the
      OSAS patient group. RESULTS: Median serum S100B protein level was 133.7 pg/ mL
      (range 20.97-230.70 pg/mL) in patients with OSAS and 16.1 pg/mL (range 10.1-22.9
      pg/mL) in the control group (p < 0.005). Serum S100B protein level did not
      correlate with any studied variable (p > 0.05 for each correlation coefficient).
      CONCLUSIONS: Serum S100B protein level is increased in patients with OSAS and may
      be a useful biochemical marker in those patients.

PMID- 23161190
TI  - Synovial cysts of the lumbar spine.
AB  - BACKGROUND AND PURPOSE: Synovial cysts of the spine occur most frequently in the
      lumbosacral region. Methods of treatment vary, but in cases of chronic pain or
      neurological deficits surgical intervention is undertaken. The aim of this paper
      is to present indications, surgical technique and efficacy of surgical treatment
      in patients with synovial cyst of the spinal canal. MATERIAL AND METHODS: The
      retrospective analysis included 11 patients, aged from 47 to 72 years, treated at
      the Department of Neurosurgery and Neurotraumatology, Poznan University of
      Medical Sciences, between 2004 and 2009. The length of medical history ranged
      from 2 months to 6 years. Conservative treatment applied before surgery was not
      effective. Neurological examination revealed unilateral or bilateral sciatica,
      superficial sensory disturbance or lower limb paresis. RESULTS: Synovial cysts
      were located mainly at the L4-L5 level (9 cases). Magnetic resonance imaging
      (MRI) of the spine was performed in all patients and showed the cystic lesion
      attached to the intervertebral joint. Surgical treatment consisted of a
      unilateral fenestration using microsurgical techniques in most cases. Back pain
      relief was observed in 9 cases. In 10 patients, symptoms of sciatica disappeared.
      Neurological deficits disappeared in 5 patients. CONCLUSIONS: Surgical treatment
      of spinal synovial cysts is safe, effective and ensures a long-lasting effect.
      Surgical treatment is indicated in patients in whom the clinical symptoms
      correlate with the presence of synovial cyst in imaging studies and do not
      resolve after conservative treatment.

PMID- 23161191
TI  - Diffusion tensor imaging in Alzheimer disease and mild cognitive impairment.
AB  - A wide range of imaging studies provides growing support for the potential role
      of diffusion tensor imaging (DTI) in evaluating microstructural white matter
      integrity in Alzheimer disease (AD) and mild cognitive impairment (MCI). Our
      review aims to present DTI principles, post-processing and analysis frameworks
      and to report the results of particular studies.   The distribution of AD-related
      white matter abnormalities is widely discussed in the light of deteriorated
      connectivity within certain tracts due to secondary white matter degeneration;
      primary alterations are also assumed to contribute to the pattern. The question
      whether it is more effective to assess the whole-brain diffusion or to directly
      concentrate on specific regions remains an interesting issue. Assessing white
      matter microstructure alterations, as evaluated by group-level differences of
      tensor-derived parameters, may be a promising neuroimaging tool for differential
      diagnosis between AD, MCI and other cognitive disorders, as well as being
      particularly helpful in the interpretation of underlying pathological processes.

PMID- 23161192
TI  - Burden and quality of life in caregivers of persons with multiple sclerosis.
AB  - Multiple sclerosis (MS) is the second most common cause of disability among
      nervous system diseases. This disease causes reduced quality of life of patients
      and those caring for them. Quality of life (QoL) measures consist of at least
      three broad domains: physical, mental and social. In the field of medicine,
      researchers have often used the concept of health-related quality of life, which
      specifically focuses on the impact of an illness and/or treatment on patients'
      perception of their status of health and on subjective well-being or satisfaction
      with life.   Subjective factors of QoL in MS patients include perception of
      symptoms, level of fitness, self-image, satisfaction with family life, work, the
      economic situation, interaction with other people, social support and life in
      general. Objective factors include the clinical picture of disease, social
      status, social and living conditions and the number and intensity of social
      contacts. While many generic and specific questionnaires have been developed to
      assess QoL in patients with MS, including general fatigue, there is a lack of
      specific questionnaires assessing QoL of caregivers.  In this paper, a review of
      selected studies on QoL and caregiver burden in MS and a summary of the most
      popular questionnaires measuring burden and QoL are presented. Special attention
      is paid to the first questionnaire specific for QoL of carers of persons with MS,
      CAREQOL-MS by Benito-Leon et al.

PMID- 23161193
TI  - Primary spinal primitive neuroectodermal tumour: report of two cases mimicking
      neurofibroma and review of the literature.
AB  - Primary spinal primitive neuroectodermal tumours (PNETs) are a rare entity. Most
      of them occur in children and young adults. To date, 47 cases of primary spinal
      PNET have been reported in the literature. We present two cases of primary spinal
      PNET. In both cases, the tumours were thoracic extradural ones with intrathoracic
      extension through intervertebral foramina resembling neurofibroma. These tumours
      are highly aggressive with rapid growth as evidenced by the short history in both
      of our cases. Both cases underwent gross total removal of the intraspinal and
      thoracic components. Postoperatively, both patients underwent cranio-spinal
      radiotherapy.  A review of the literature shows that the overall prognosis of
      PNETs of the spinal cord is very poor even with adequate surgery, radiotherapy
      and chemotherapy. One patient died after 4 months and the other one is still
      alive 8 months after surgery, radiotherapy and chemotherapy.

PMID- 23161194
TI  - Primary intracranial basaloid squamous cell carcinoma: an enigma.
AB  - Primary intracranial squamous cell carcinoma is extremely rare, with most cases
      arising from malignant transformation of dysembryogenetic lesions such as
      epidermoid and dermoid cysts. Intracranial squamous cell neoplasm arising de novo
      is even rarer and has been reported in only four patients to date. We herein
      describe a case of primary intracranial squamous cell carcinoma arising de novo
      in the right frontal lobe in a 35-year-old woman treated with a combination of
      surgery and postoperative conformal radiation. We have also shed light on the
      biology and the therapeutic options of this enigmatic tumour.

PMID- 23161195
TI  - Multiple spinal cavernous malformations in Klippel-Trenaunay-Weber syndrome.
AB  - Klippel-Trenaunay-Weber syndrome (KTWS) is a rare, congenital vascular disorder
      characterized by cutaneous haemangiomas, venous varicosities, and hypertrophy of
      the osseous and soft tissue. Various vascular anomalies of the central nervous
      system have been described in this syndrome. Two previous associations between
      KTWS and spinal cord cavernous malformations have been reported in the English
      literature.  In this report, we present a patient in whom multiple cavernous
      malformations located in the conus medullaris region and cauda equina were
      associated with KTWS. General physical examination as well as neuroradiological
      and operative findings are described.

PMID- 23161196
TI  - Anhelation due to formation of tuberculomas at the medulla oblongata during
      chemotherapy of tuberculous meningitis.
AB  - Formation of tuberculoma is a rare response of neurotuberculosis in patients
      regularly and adequately treated with anti-tuberculous drugs. We report a 13-year
      old girl with two tuberculomas which formed in the dorsal part of the medulla
      oblongata during chemotherapy for tuberculous meningitis. The tuberculomas were
      both removed via a suboccipital midline approach and were demonstrated by
      pathological findings but the girl died of cardiac arrest that was thought to be
      caused by postoperative medulla oblongata oedema. In combination with a
      literature review, we discuss the clinical features and treatment options of
      brainstem tuberculomas.

PMID- 23161197
TI  - Selective enrichment of catecholamines using iron oxide nanoparticles followed by
      CE with UV detection.
AB  - This study examines the use of unmodified magnetite nanoparticles (Fe(3)O(4) NPs)
      for selective extraction and enrichment of the catecholamines dopamine (DA),
      noradrenaline (NE), and adrenaline (E), prior to analysis using capillary
      electrophoresis with UV detection. Coordination between Fe(3+) on-the-surface
      Fe(3)O(4) NPs and the catechol moiety of catecholamines enables Fe(3)O(4) NPs to
      capture catecholamines from an aqueous solution. We obtained maximum loading of
      catecholamines on the NP surface by adjusting the pH of the solution to 7.0. In
      addition, catecholamine loading on the Fe(3)O(4) NPs increased in conjunction
      with NP concentrations. H(3)PO(4) was found to be efficient for the removal of
      adsorbed catecholamines on the NP surface. Adding 1.2%
      poly(diallyldimethylammonium chloride) to the background electrolyte resulted in
      a baseline separation of the liberated catecholamines within 20 min. Under
      optimal extraction and separation conditions, the limit of detections at a S/N
      ratio of 3 for E, NE, and DA were 9, 8, and 10 nM, respectively. Significantly,
      the combination of a phenylboronate-containing spin column and the proposed
      method was successfully applied to the determination of NE and DA in human urine
      and NE in Portulaca oleracea L. leaves.

PMID- 23161198
TI  - Trichome-specific expression of the amorpha-4,11-diene 12-hydroxylase (cyp71av1)
      gene, encoding a key enzyme of artemisinin biosynthesis in Artemisia annua, as
      reported by a promoter-GUS fusion.
AB  - Artemisinin derivatives are effective anti-malarial drugs. In order to design
      transgenic plants of Artemisia annua with enhanced biosynthesis of artemisinin,
      we are studying the promoters of genes encoding enzymes involved in artemisinin
      biosynthesis. A 1,151 bp promoter region of the cyp71av1 gene, encoding amorpha
      4,11-diene 12-hydroxylase, was cloned. Alignment of the cloned promoter and other
      cyp71av1 promoter sequences indicated that the cyp71av1 promoter may be different
      in different A. annua varieties. Comparison to the promoter of amorpha-4,11-diene
      synthase gene showed a number of putative cis-acting regulatory elements in
      common, suggesting a co-regulation of the two genes. The cyp71av1 promoter
      sequence was fused to the beta-glucuronidase (GUS) reporter gene and two
      varieties of A. annua and Nicotiana tabacum were transformed. In A. annua, GUS
      expression was exclusively localized to glandular secretory trichomes (GSTs) of
      leaf primordia and top expanded leaves. In older leaves, there is a shift of
      expression to T-shaped trichomes (TSTs). Only TSTs showed GUS staining in lower
      leaves and there is no GUS staining in old leaves. GUS expression in flower buds
      was specifically localized to GSTs. The recombinant promoter carries the cis
      acting regulatory elements required for GST-specific expression. The cyp71av1
      promoter shows activity in young tissues. The recombinant promoter was up to 200
      times more active than the wild type promoter. GUS expression in transgenic N.
      tabacum was localized to glandular heads. Transcript levels were up-regulated by
      MeJA. Wound responsiveness experiment showed that the cyp71av1 promoter does not
      appear to play any role in the response of A. annua to mechanical stress.

PMID- 23161199
TI  - A genome-wide BAC end-sequence survey of sugarcane elucidates genome composition,
      and identifies BACs covering much of the euchromatin.
AB  - BAC-end sequences (BESs) of hybrid sugarcane cultivar R570 are presented. A total
      of 66,990 informative BESs were obtained from 43,874 BAC clones. Similarity
      search using a variety of public databases revealed that 13.5 and 42.8 % of BESs
      match known gene-coding and repeat regions, respectively. That 11.7 % of BESs are
      still unmatched to any nucleotide sequences in the current public databases
      despite the fact that a close relative, sorghum, is fully sequenced, indicates
      that there may be many sugarcane-specific or lineage-specific sequences. We found
      1,742 simple sequence repeat motifs in 1,585 BESs, spanning 27,383 bp in length.
      As simple sequence repeat markers derived from BESs have some advantages over
      randomly generated markers, these may be particularly useful for comparing BAC
      based physical maps with genetic maps. BES and overgo hybridization information
      was used for anchoring sugarcane BAC clones to the sorghum genome sequence. While
      sorghum and sugarcane have extensive similarity in terms of genomic structure,
      only 2,789 BACs (6.4 %) could be confidently anchored to the sorghum genome at
      the stringent threshold of having both-end information (BESs or overgos) within
      300 Kb. This relatively low rate of anchoring may have been caused in part by
      small- or large-scale genomic rearrangements in the Saccharum genus after two
      rounds of whole genome duplication since its divergence from the sorghum lineage
      about 7.8 million years ago. Limiting consideration to only low-copy matches,
      1,245 BACs were placed to 1,503 locations, covering ~198 Mb of the sorghum genome
      or about 78 % of the estimated 252 Mb of euchromatin. BESs and their analyses
      presented here may provide an early profile of the sugarcane genome as well as a
      basis for BAC-by-BAC sequencing of much of the basic gene set of sugarcane.

PMID- 23161200
TI  - Influence of high-conductivity buffer composition on field-enhanced sample
      injection coupled to sweeping in CE.
AB  - The aim of this work was to clarify the mechanism taking place in field-enhanced
      sample injection coupled to sweeping and micellar EKC (FESI-Sweep-MEKC), with the
      utilization of two acidic high-conductivity buffers (HCBs), phosphoric acid or
      sodium phosphate buffer, in view of maximizing sensitivity enhancements. Using
      cationic model compounds in acidic media, a chemometric approach and simulations
      with SIMUL5 were implemented. Experimental design first enabled to identify the
      significant factors and their potential interactions. Simulation demonstrates the
      formation of moving boundaries during sample injection, which originate at the
      initial sample/HCB and HCB/buffer discontinuities and gradually change the
      compositions of HCB and BGE. With sodium phosphate buffer, the HCB conductivity
      increased during the injection, leading to a more efficient preconcentration by
      staking (about 1.6 times) than with phosphoric acid alone, for which conductivity
      decreased during injection. For the same injection time at constant voltage,
      however, a lower amount of analytes was injected with sodium phosphate buffer
      than with phosphoric acid. Consequently sensitivity enhancements were lower for
      the whole FESI-Sweep-MEKC process. This is why, in order to maximize sensitivity
      enhancements, it is proposed to work with sodium phosphate buffer as HCB and to
      use constant current during sample injection.

PMID- 23161201
TI  - Hormonal male contraception: end of a dream or start of a new era?

PMID- 23161203
TI  - Gamma-hydroxybutyrate (GHB) and topiramate--clinically relevant drug interaction
      suggested by a case of coma and increased plasma GHB concentration.

PMID- 23161202
TI  - Age-related changes in body composition and their relationship with bone mineral
      density decreasing rates in central south Chinese postmenopausal women.
AB  - The purpose of this work is to investigate the age-related changes in body
      composition and their relationship with bone mineral density decreasing rates
      (BDR) in central south Chinese postmenopausal women. BDR is the percentage of
      bone mineral density (BMD) decreasing value relative to the peak bone mass. A
      cross-sectional study was conducted on 779 healthy postmenopausal women, aged 50
      77. Lumbar spine, total hip, and femoral neck BMD and body composition were
      measured by dual-energy X-ray absorptiometry. In women under 65, lean mass levels
      showed a stable downward trend, and were significantly higher than those of the
      65-70 and >70 age groups; however, the fat mass levels showed no significant
      difference between the age groups. After controlling for age, age at menopause,
      and height, both fat mass and lean mass positively correlated with BDR at the
      lumbar1-4 spine, the femoral neck and the total hip. When BDR at the lumbar1-4
      spine was used as the dependent variable, a higher R (2) change and partial R (2)
      were seen in fat mass than the age, age at menopause or lean mass, indicating
      that fat mass was the most significant determinant of BDR at this site. When BDR
      at the femoral neck or total hip was used as the dependent variable,
      respectively, lean mass was a more significant determinant than that of fat mass.
      We found that with advancing age, lean mass begins to decrease in women aged over
      65 years, but fat mass levels show no significant difference between the age
      groups. Both fat mass and lean mass positively correlate with BDR, with site
      specific differences. Fat mass is the most significant determinant of BDR at the
      lumbar spine, whereas lean mass is the most significant determinant of BDR at the
      femoral neck and total hip.

PMID- 23161204
TI  - Crystallization using reverse micelles and water-in-oil microemulsion systems:
      the highly selective tool for the purification of organic compounds from complex
      mixtures.
AB  - The active pharmaceutical ingredient orlistat is usually manufactured using a
      semi-synthetic procedure, producing crude product and complex mixtures of highly
      related impurities with minimal side-chain structure variability. It is therefore
      crucial for the overall success of industrial/pharmaceutical application to
      develop an effective purification process. In this communication, we present the
      newly developed water-in-oil reversed micelles and microemulsion system-based
      crystallization process. Physiochemical properties of the presented
      crystallization media were varied through surfactants and water composition, and
      the impact on efficiency was measured through final variation of these two
      parameters. Using precisely defined properties of the dispersed water phase in
      crystallization media, a highly efficient separation process in terms of
      selectivity and yield was developed. Small-angle X-ray scattering, high
      performance liquid chromatography, mass spectrometry, and scanning electron
      microscopy were used to monitor and analyze the separation processes and orlistat
      products obtained. Typical process characteristics, especially selectivity and
      yield in regard to reference examples, were compared and discussed.

PMID- 23161205
TI  - Cell polarity and cystic kidney disease.
AB  - Epithelial cell polarity is essential for organ development; aberrations in this
      process have been implicated in various diseases, including polycystic kidney
      disease. Establishment and maintenance of cell polarity is governed by a number
      of molecular processes and how these processes operate remains an interesting
      question. Conserved protein complexes guide both apical-basolateral polarity and
      planar cell polarity. In this review we discuss the recent findings that provide
      insights into polarity mechanisms and the intriguing crosstalk between apical
      basolateral polarity and planar cell polarity, and their relationship to cystic
      kidney disease. 

PMID- 23161206
TI  - Phosphate is a vascular toxin.
AB  - Elevated phosphate (P) levels are seen in advanced renal failure and, together
      with dysregulated calcium, parathyroid hormone and vitamin D levels, contribute
      to the complex of chronic kidney disease-mineral and bone disease (CKD-MBD).
      Converging evidence from in vitro, clinical and epidemiological studies suggest
      that increased P is associated with vascular calcification and mortality. When
      vessels are exposed to high P conditions in vitro, they develop apoptosis,
      convert to bone-like cells and develop extensive calcification. Clinical studies
      in children on dialysis show that high P is associated with increased vessel wall
      thickness, arterial stiffness and coronary calcification. Epidemiological studies
      in adult dialysis patients demonstrate a significant and independent association
      between raised P and mortality. Importantly, raised P is associated with
      cardiovascular changes even in pre-dialysis CKD, and also in subjects with normal
      renal function but high P. All P binders can effectively reduce serum P, and this
      decrease is linked to improved survival. Raised serum P triggers the release of
      fibroblast growth factor 23 (FGF-23), which has the beneficial effect of
      increasing P excretion in early CKD, but is increased several 1,000-fold in
      dialysis, and may be an independent cardiovascular risk factor. Both FGF-23 and
      its co-receptor Klotho may have direct effects on the vasculature leading to
      calcification. Fascinatingly, disturbances in FGF-23-Klotho and raised P have
      also been associated with premature aging. These data suggest that high P levels
      have adverse vascular effects and that maintaining the serum P levels in the
      normal range reduces cardiovascular risk and mortality.

PMID- 23161207
TI  - Cytokines in chronic kidney disease: potential link of MCP-1 and dyslipidemia in
      glomerular diseases.
AB  - BACKGROUND: Many studies have indicated a role for cytokines in chronic kidney
      disease (CKD). The aim of this study was to evaluate plasma and urinary levels of
      monocyte chemoattractant protein-1 (MCP-1/CCL2), transforming growth factor-beta1
      (TGF-beta1), and interleukin-8 (IL-8/CXCL8) in pediatric patients with CKD stages
      2-4. METHODS: Cytokines were measured in 37 healthy controls and in 42 CKD
      patients by enzyme-linked immunoassay. Patients were divided into groups
      according to CKD etiology: glomerular disease (group 1, n = 11) and congenital
      anomalies of the kidney and urinary tract (group 2, n = 31). Urinary cytokine
      measurements were standardized for creatinine. RESULTS: Plasma and urinary levels
      of MCP-1/CCL2 were significantly higher in both CKD groups compared to the
      control group. Between the two CKD groups, only urinary MCP-1/CCL2 levels were
      significantly different, with MCP-1/CCL2 levels higher in group 1 patients.
      Plasma and urinary levels of IL-8/CXCL8 and TGF-beta1 were undetectable in the
      control group but comparable between the two CKD groups. In group 1 patients,
      urinary MCP-1/CCL2 levels were negatively correlated to serum albumin levels and
      positively correlated to the levels of total cholesterol and triglycerides. In
      group 2 patients, urinary levels of IL-8/CXCL8 were negatively correlated with
      the estimated glomerular filtration rate and positively correlated with body mass
      index. CONCLUSIONS: Differences in cytokine profiles may be related to CKD
      etiology and other disease-associated alterations.

PMID- 23161208
TI  - The role of jails in engaging PLWHA in care: from jail to community.
AB  - HIV testing in jails has provided public health officials with the opportunity to
      not only identify new cases of HIV but to also reestablish contact with
      previously diagnosed individuals, many of whom never entered care following
      diagnosis or entered care but then dropped out. The presence of inmates
      throughout the HIV/AIDS continuum of care suggests that jails can play a
      strategic role in engaging persons living with HIV and AIDS in care. In order to
      be successful in structuring HIV/AIDS programs in jails, health care and
      correctional officials will be well-served to: (1) understand the HIV/AIDS
      continuum of care from the standpoint of engagement interventions that promote
      participation; (2) be aware of jail, community, and prison interventions that
      promote engagement in care; (3) anticipate and plan for the unique barriers jails
      provide in implementing engagement interventions; and, (4) be creative in
      designing engagement interventions suitable for both newly and previously
      diagnosed individuals. 

PMID- 23161209
TI  - HIV knowledge and sexual risk behavior among pregnant couples in South Africa:
      the PartnerPlus project.
AB  - In sub-Saharan Africa, 60 % of people living with HIV are women and most are of
      childbearing age. Alarmingly, seroconversion rates during pregnancy are high and
      increase as pregnancy progresses, highlighting the importance of increasing HIV
      knowledge among pregnant women and their partners. This study compared sexual
      risk behavior, HIV knowledge and condom use pre- to post-partum among South
      African couples (n = 239 couples) randomly assigned to an intervention or an
      enhanced standard of care with the PMTCT protocol at rural community health
      antenatal clinics. Consistent condom use and HIV-related knowledge increased
      baseline to post-intervention and was maintained at long term follow up post
      partum among participants in the intervention condition. HIV knowledge mediated
      the relationship between the intervention and consistent condom use. Results from
      this pilot study provide support for the integration of HIV risk reduction
      interventions for both women and men into existing PMTCT services during and
      following pregnancy.

PMID- 23161210
TI  - Correlates of retention in HIV care after release from jail: results from a multi
      site study.
AB  - Retention in care is key to effective HIV treatment, but half of PLWHA in the US
      are continuously engaged in care. Incarcerated individuals are an especially
      challenging population to retain, and empiric data specific to jail detainees is
      lacking. We prospectively evaluated correlates of retention in care for 867 HIV
      infected jail detainees enrolled in a 10-site demonstration project. Sustained
      retention in care was defined as having a clinic visit during each quarter in the
      6 month post-release period. The following were independently associated with
      retention: being male (AOR = 2.10, p <= 0.01), heroin use (AOR 1.49, p = 0.04),
      having an HIV provider (AOR 1.67, p = 0.02), and receipt of services: discharge
      planning (AOR 1.50, p = 0.02) and disease management session (AOR 2.25, p <=
      0.01) during incarceration; needs assessment (AOR 1.59, p = 0.02), HIV education
      (AOR 2.03, p <= 0.01), and transportation assistance (AOR 1.54, p = 0.02) after
      release. Provision of education and case management services improve retention in
      HIV care after release from jail.

PMID- 23161211
TI  - Capillary electromigration based techniques in diagnostics of prion protein
      caused diseases.
AB  - Transmissible spongiform encephalopathies are a group of fatal neurodegenerative
      diseases with long incubation time. This group includes Creutzfeld-Jakob disease,
      kuru, scrapie, chronic wasting disease, and bovine spongiform encephalopathy.
      Sensitive and specific detection of abnormal prion protein as "a source agent" of
      the above-mentioned diseases in blood could provide a diagnostic test or a
      screening assay for animal and human prion protein diseases diagnostics.
      Therefore, diagnostic tests for prion protein diseases represent unique challenge
      requiring development of novel assays exploiting properties of prion protein
      complex. Presently, diagnostic methods such as protein misfolding cyclic
      amplification, conformation-dependent immunoassay, dissociation-enhanced
      lanthanide fluorescent immunoassay, fluorescence correlation spectroscopy, and/or
      flow microbead immunoassay are used for abnormal prion protein (PrP(Sc) )
      detection. On the other hand, using of CE for PrP(Sc) detection in body fluids is
      an attractive alternative; it has been already applied for the blood samples of
      infected sheep, elk, chimpanzee, as well as humans. In this review, assays for
      prion protein detection are summarized with special attention to capillary
      electromigration based techniques, such as CE, CIEF, and/or CGE. The potential of
      the miniaturized and integrated lab-on-chip devices is highlighted, emphasizing
      recent advances of this field in the proteomic analysis.

PMID- 23161213
TI  - Determinants of utilization of sufficient tetanus toxoid immunization during
      pregnancy: evidence from the Kenya Demographic and Health Survey, 2008-2009.
AB  - Although the effectiveness of tetanus toxoid (TT) immunization during pregnancy
      in preventing maternal and neonatal tetanus is well established, in many
      developing countries, TT immunization programs are underutilized. The objective
      of this study was to examine factors associated with sufficient TT immunization
      among postpartum women in Kenya. Population based secondary data analysis was
      conducted using de-identified data from the 2008-2009 Kenyan Demographic and
      Health Survey (KDHS) for 1,370 female participants who had a live birth during or
      within 12 months of the cross-sectional survey. Chi-square test and independent
      sample t test were conducted to assess bivariate associations and a multivariable
      logistic regression analysis was conducted to examine associations before and
      after adjustment for demographic, socioeconomic, cultural, and access to care
      factors. The main factors contributing to having been sufficiently immunized
      against tetanus were lower birth order, higher household wealth index, women's
      employment, making joint health-related decisions with a partner, and higher
      number of antenatal care visits. Implications for health care providers and other
      professionals involved in development of strategies and interventions aimed at
      improving immunization rates are discussed.

PMID- 23161214
TI  - Quantification abilities in angelfish (Pterophyllum scalare): the influence of
      continuous variables.
AB  - Previous studies investigating quantity discrimination have shown that angelfish
      are able to select the larger of two groups of conspecifics (shoals). The
      discrimination limits shown by angelfish were similar to those found for other
      vertebrates when large (>=4) and small quantities (<4) were presented. However,
      in these studies, no attempt was made to control for non-numerical features of
      the stimulus shoals and thus the question whether numerical or some quantitative
      attributes of the shoals were utilized for making the choices could not be
      answered. Here, we investigate whether angelfish can discriminate between shoals
      differing in numerical size using non-numerical attributes. We systematically
      manipulate density, inter-fish distance, and overall space occupied by the
      shoals, one factor at a time, and analyse the choices angelfish made between the
      contrasting stimulus shoals. The stimulus shoals consisted of contrasts between
      large (10 vs. 5) and small (3 vs. 2) number of conspecifics. We found density to
      be a sufficient condition for discrimination between large shoals as the test
      subjects preferred the more dense shoal. Manipulation of inter-fish distance
      indicated that this variable is not a necessary factor in discrimination at
      either shoal size contrast. Likewise, we found that the size of space occupied by
      the contrasted shoals also did not significantly influence discrimination.
      Sensitivity to the density of large shoals indicates that angelfish can
      discriminate shoal size using this non-numerical cue. Nevertheless, the factors
      we examined may represent only a subset of all possible non-numerical features
      upon which angelfish may base their discrimination. Thus, we suggest that further
      research is required to clarify whether and under what circumstances angelfish
      may use numerical or non-numerical features when discriminating between shoals of
      differing size.

PMID- 23161212
TI  - Community health education at student-run clinics leads to sustained improvement
      in patients' hepatitis B knowledge.
AB  - While student-run clinics are often important healthcare safety nets for
      underserved populations, their efficacy for improving patient health knowledge
      has not been thoroughly explored. From September 2011 to April 2012, we assessed
      patients' retention of hepatitis B virus (HBV) knowledge after receiving student
      led education at two student-run HBV screening and vaccination clinics. Patient
      education was provided by trained first and second-year medical, nursing, and
      pharmacy students, aided by a script and interpreters. Patient knowledge of HBV
      was evaluated at three points: before education, after the initial visit, and at
      one-month follow-up. Student-led education produced improved knowledge of HBV
      transmission, prevention, and management, which was retained 1 month after
      education for 52 patients tracked through time. Mean scores on an HBV knowledge
      survey improved from 56.4 % (SD = 15.2 %) at baseline to 66.6 % (SD = 15.1 %)
      after education, and 68.3 % (SD = 15.2 %) after one month. There was a
      statistically significant difference between the first and second (paired T test,
      p < 0.001) and the first and third tests (paired T test, p < 0.001), but no
      difference between the second and third tests (paired T test, p = 0.45).
      Multivariate analysis demonstrated that retention was correlated with patient
      educational background but independent of patient age, gender, income, primary
      language and number of years lived in the United States. Our study suggests that
      trained health professional students can effectively impart health knowledge that
      is retained by patients for at least 1 month. These results warrant consideration
      of student-led educational sessions at SRCs as a promising community health
      education model.

PMID- 23161215
TI  - Ontogeny of object permanence in a non-storing corvid species, the jackdaw
      (Corvus monedula).
AB  - The aim of the present study was to investigate the ontogeny of object permanence
      in a non-caching corvid species, the jackdaw (Corvus monedula). Jackdaws are
      often presented as typical examples of non-storing corvids, as they cache either
      very little or not at all. We used Uzgiris and Hunt's Scale 1 tasks to determine
      the age at which the certain stages set in and the final stage of this capacity
      that is reached. Our results show that the lack of food-storing behaviour is not
      associated with inferior object permanence abilities in the jackdaw, as our
      subjects (N = 19) have reached stage 5 competence (to follow successive visible
      displacements) at the average age of 61 days post-hatch and showed some evidence
      of stage 6 competence (to follow advanced invisible displacements) at 81 days
      post-hatch and thereafter. As we appreciate that object permanence abilities have
      a very wide ecological significance, our positive results are probably the
      consequence of other, more fundamental ecological pressures, such as nest-hole
      reproduction or prey-predator interactions.

PMID- 23161216
TI  - The role of voltage-gated potassium channels Kv2.1 and Kv2.2 in the regulation of
      insulin and somatostatin release from pancreatic islets.
AB  - The voltage-gated potassium channels Kv2.1 and Kv2.2 are highly expressed in
      pancreatic islets, yet their contribution to islet hormone secretion is not fully
      understood. Here we investigate the role of Kv2 channels in pancreatic islets
      using a combination of genetic and pharmacologic approaches. Pancreatic beta
      cells from Kv2.1(-/-) mice possess reduced Kv current and display greater glucose
      stimulated insulin secretion (GSIS) relative to WT beta-cells. Inhibition of
      Kv2.x channels with selective peptidyl [guangxitoxin-1E (GxTX-1E)] or small
      molecule (RY796) inhibitors enhances GSIS in isolated wild-type (WT) mouse and
      human islets, but not in islets from Kv2.1(-/-) mice. However, in WT mice neither
      inhibitor improved glucose tolerance in vivo. GxTX-1E and RY796 enhanced
      somatostatin release in isolated human and mouse islets and in situ perfused
      pancreata from WT and Kv2.1(-/-) mice. Kv2.2 silencing in mouse islets by
      adenovirus-small hairpin RNA (shRNA) specifically enhanced islet somatostatin,
      but not insulin, secretion. In mice lacking somatostatin receptor 5, GxTX-1E
      stimulated insulin secretion and improved glucose tolerance. Collectively, these
      data show that Kv2.1 regulates insulin secretion in beta-cells and Kv2.2
      modulates somatostatin release in delta-cells. Development of selective Kv2.1
      inhibitors without cross inhibition of Kv2.2 may provide new avenues to promote
      GSIS for the treatment of type 2 diabetes.

PMID- 23161220
TI  - A review of developments in the methodology and application of microemulsion
      electrokinetic chromatography.
AB  - MEEKC is a mode of CE, which utilizes microemulsion (ME) as the BGE to achieve
      separation of a diverse range of analytes. MEs are composed of nanometer-sized
      oil droplets suspended in aqueous buffer which are stabilized by the presence of
      a surfactant and co-surfactant. These MEs are commonly referred to as oil-in
      water MEs and their application in MEEKC has been extensively examined. This
      review details advances in the theory, methodology, and application of MEEKC
      during the period 2010-2012. Areas covered include online sample concentration,
      advances in chiral separations, use of coated capillaries, chemometric
      approaches, and the use of novel additives to the ME system. This review also
      provides the reader with an introduction to MEEKC and a presentation of recent
      applications.

PMID- 23161217
TI  - Suramin decreases injury and improves regeneration of ethanol-induced steatotic
      partial liver grafts.
AB  - Steatotic grafts are excluded for use in partial liver transplantation (LT)
      because of the increased risk of primary nonfunction. This study investigated the
      effects of suramin, a polysulfonated naphthylurea, on the outcome of steatotic
      partial LT. Rat livers were harvested after acute ethanol treatment (6 g/kg,
      intragastric administration), reduced in size to ~ 1/3, and transplanted. Serum
      alanine aminotransferase (ALT) and total bilirubin levels as well as hepatic
      necrosis and apoptosis were significantly higher after transplantation of fatty
      partial grafts (FPG) than lean partial grafts (LPG). Suramin (5 mg/kg, i.p.)
      decreased ALT by ~ 60%, hyperbilirubinemia by 75%, necrosis by 83%, and apoptosis
      by 70% after FPG transplantation. Hepatic cellular 5-bromo-2'-deoxyuridine (BrdU)
      incorporation increased to 28% in LPG but was only 2% in FPG at 48 hours, and the
      mitotic index increased to 7% in LPG but was only 0.2% in FPG, indicating
      suppressed regeneration in FPG. Suramin increased BrdU incorporation and the
      mitotic index to 43% and 9%, respectively, in FPG. All FPG recipients died within
      5 days. Suramin recovered survival of FPG to 62%. Tumor necrosis factor-alpha
      (TNF-alpha) mRNA was 2.2-fold higher in FPG than in LPG and was associated with
      activation of caspase-8 and caspase-3 in FPG. Suramin decreased TNF-alpha and
      caspase activation in FPG. Transforming growth factor-beta (TGF-beta), phospho
      Smad2/3 and p21Cip1 were significantly higher in FPG than in LPG and suramin
      blocked TGF-beta formation and its down-stream signaling pathway. Taken together,
      suramin improves the outcome of FPG transplantation, most likely by inhibition of
      TNF-alpha and TGF-beta formation.

PMID- 23161221
TI  - Enhanced suppression of proliferation and migration in highly-metastatic lung
      cancer cells by combination of valproic acid and coumarin-3-carboxylic acid and
      its molecular mechanisms of action.
AB  - Valproic acid (VPA) as a broad-spectrum inhibitor of histone deacetylase, has
      been used in cancer therapy. Recently, the combination of VPA with other
      anticancer agents has been considered as a useful and necessary strategy to
      inhibit tumor growth and progression. The coumarin derivates from natural plants
      have been shown to be the promising natural anticancer agents. However, no
      literature is available on the anticancer effects of the combination of VPA and
      coumarin-3-carboxylic acid (HCCA). Here we show that this combination
      significantly increases inhibitory effects against the proliferation and
      migration in highly-metastatic lung cancer cells by inducing apoptosis and cell
      cycle arrest as well as regulating related protein expressions. Our results
      indicate that this combination of VPA with HCCA not only enhances the protein
      levels of Bax, cytosolic cytochrome c, caspase-3 and PARP-1 but also reduces the
      protein expressions of Bcl-2, cyclin D1 and NF-kappaB as well as inhibits the
      phosphorylation and expressions of Akt, EGFR, VEGFR2 and c-Met in the cancer
      cells. Our results suggest that the combination of VPA with HCCA suppresses the
      proliferation and migration of lung cancer cells via EGFR/VEGFR2/c-Met-Akt-NF
      kappaB signaling pathways; this combination may have a wide therapeutic and/or
      adjuvant therapeutic application in the treatment of lung cancer. 

PMID- 23161223
TI  - Giant condyloma acuminatum of vulva treated by surgical excision and
      reconstruction of defect.

PMID- 23161222
TI  - Role of phytoestrogenic oils in alleviating osteoporosis associated with
      ovariectomy in rats.
AB  - The objective of this study was to elucidate the effect of soybean oil (SbO) and
      sesame oil (SO) supplemented diets on bone biomarkers changes in OVX
      (ovariectomized) rats. The current data exhibited significant decrease in BMD
      (bone mineral density), accompanied with marked depletion in the level of Ca, P
      and Mg in both serum and bone of OVX rats. Also, serum estrogen, total protein,
      HDL-C (high density lipoprotein cholesterol), bone NO levels were decreased in
      OVX rats. However, a significant increase in the level of serum TL (total
      lipids), TC (total cholesterol), TG (triglycerides), LDL-C (low density
      lipoprotein cholesterol), VLDL-C (very low density lipoprotein cholesterol),
      urine minerals (Ca, P, Mg), as well as serum, bone and urine ALP (alkaline
      phosphatase) and ACP (acid phosphatase) activity were recorded in OVX rats.
      Further changes were also detected by the increased level of urine
      hydroxyproline, serum parathyroid hormone and osteocalcin, as well as urea and
      creatinine level in both serum and urine. On the other hand, when OVX rats were
      fed on SbO (soy bean oil) (15 % w/w) or SO (sesame oil) (10 % w/w) supplemented
      diets, the data recorded a significant improvement in all the above mentioned
      parameters. So, it can be concluded that consumption of SbO or SO supplemented
      diets might be considered as a functional food for retarding risks of
      osteoporosis associated with estrogen deficiency in OVX states. 

PMID- 23161224
TI  - The transverse section of the fetus urinary bladder is circular and, for volume
      estimation, an appropriate longitudinal section is sufficient.
AB  - PURPOSE: The purpose was to investigate the transverse shape of the fetal urinary
      bladder. METHODS: Using 3D ultrasound, an appropriate longitudinal image of fetal
      urinary bladders was chosen. Perpendicular sections were examined and the
      transverse bladder image with a minimum of shadows was selected, documented and
      transferred to a PC. The contour of the transverse bladder image was marked
      manually and recorded electronically. The mean of radii distances from the centre
      pixel to each border pixel outlining this bladder image was calculated for each
      fetus. RESULTS: In the material comprising 20 fetuses, the range of mean radii
      was 2.6-18.4 mm and the SD 0.4 mm. The mean wall thickness of the bladders was
      2.7 mm and the distance represented by one pixel for different selected depths
      was 0.3 mm on average. CONCLUSIONS: In view of the current technical limitations,
      an aberration from the circular shape may not be discernible. For this reason,
      the transverse shape of the fetal urinary bladder can be regarded as a circle.
      This means that, for bladder volume estimation, only an appropriate longitudinal
      section is necessary.

PMID- 23161225
TI  - Management and reproductive outcome of complete septate uterus with duplicated
      cervix and vaginal septum: review of 21 cases.
AB  - AIM: To evaluate the reproductive outcomes of complete septate uterus with
      duplicated cervix and vaginal septum. METHODS: Twenty-one patients who have
      complete septate uterus with duplicated cervix and vaginal septum were
      retrospectively reviewed in this study. In Group I, 11 patients with a poor
      reproductive outcome (spontaneous miscarriage or infertility) or dyspareunia
      underwent hysteroscopic metroplasty and removal of vaginal septum with the
      preservation of cervical septum. In Group II, 10 patients without a history of
      spontaneous miscarriage did not undergo hysteroscopic transection of the uterine
      septum. Of 10, four underwent vaginal septum incision due to dyspareunia, two
      underwent mere laparoscopic pelvic adhesiolysis because of infertility, and four
      without symptoms had no intervention. The primary endpoints included the
      pregnancy rate and outcomes of pregnancies. RESULTS: In Group I, the pregnancy
      rate after surgery is 81.8 % (9/11). Of nine women who conceived, six had term
      delivery, one encountered induced abortion due to the malformation of the fetal
      heart, and two had ongoing pregnancy. In Group II, among six patients accepting
      surgery, three had term delivery. The pregnancy rate after operation is 50 %
      (3/6). CONCLUSIONS: The uterine septum may not necessarily be transected for
      patients who have complete septate uterus with duplicated cervix and vaginal
      septum, and meanwhile have no a history of poor reproductive outcome.

PMID- 23161226
TI  - Evaluation of subgroups of the human sperm hypoosmotic swelling test in
      normozoospermic male cases with recurrent fertilization failure: a prospective
      case-controlled study.
AB  - PURPOSE: To compare subgroups of the human sperm hypoosmotic swelling test
      subgroups in both recurrent fertilization negative infertile cases with normal
      semen analysis and fertilization positive controls. METHODS: This was a
      prospective case-controlled study performed with normospermic 33 previously
      fertile male (secondary infertility) and 41 infertile men who had undergone two
      or three unsuccessful in vitro fertilization attempts. HOS test was investigated
      in 4 subgroups including HOS 1, HOS 2, HOS 3, and HOS 4 according to the degree
      of sperm tail swelling and compared between the two groups. RESULTS: Four
      subgroups were compared and statistical significance was demonstrated in HOS 1,
      HOS 3 and HOS 4 tests (p < 0.001) in fertile and infertile men. Highest HOS 1 and
      lowest HOS 4 grades were determined in Group A. However, no statistical
      significance was determined between two groups in HOS 2 test which was minimal
      swelling in sperm tails. CONCLUSIONS: HOS 1, HOS 3 and HOS 4 subgroups of HOS
      test are reliable and useful methods providing important information regarding
      the sperm function. A high HOS test 1 grade plus a low HOS test 4 grade should
      suggest a fertility problem, despite a normal semen analysis. HOS test subgroups
      provide additional information in normospermic cases with unexplained
      infertility.

PMID- 23161227
TI  - A method of assessing the severity of cam type femoro-acetabular impingement in
      three dimensions.
AB  - Femoroacetabular impingement is caused by abnormal morphology of either the femur
      or acetabulum or both. Diagnostic criteria currently include an alpha angle of
      over 50 degrees  on a lateral radiograph. In this study, CT scans of symptomatic
      hips (n = 37) were compared with normal hips (n = 34) obtained from CT
      colonoscopy procedures. The femoral head described in terms of a three
      dimensional (3D) alpha angle and a 3D head neck margin (epiphysis) angle '3DMU'
      using a semi-automated algorithm. In normal hips 70% have a maximum 3Dalpha angle
      of more than 50 degrees  at some point around their femoral head (mean 53 degrees
      +/- 5 degrees , range 42 degrees  - 64 degrees ), while in cam hips, it was
      significantly larger (mean 69 degrees  +/- 10 degrees , range 54 degrees  - 94
      degrees , p<0.001). The 3DMU also varied significantly and had a reverse
      relationship to that of the alpha angle: cam hips have an articular extent that
      crossed over spherical limit of the hip joint (mean minimum 41 degrees  +/- 7
      degrees ) while the articular margin of normal hips always remained within the
      spherical limit (mean minimum 49 degrees  +/- 6 degrees ). This semi-automated
      algorithm provides an objective measure of the femoral head in health and
      disease. It can reliably distinguish cam hips from normal, enabling cam hips to
      have their cam quantified and their surgery planned objectively.

PMID- 23161229
TI  - The UV-B photoreceptor UVR8 promotes photosynthetic efficiency in Arabidopsis
      thaliana exposed to elevated levels of UV-B.
AB  - The UV-B photoreceptor UVR8 regulates expression of genes in response to UV-B,
      some encoding chloroplast proteins, but the importance of UVR8 in maintaining
      photosynthetic competence is unknown. The maximum quantum yield of PSII (F
      (v)/F(m)) and the operating efficiency of PSII (Phi(PSII)) were measured in wild
      type and uvr8 mutant Arabidopsis thaliana. The importance of specific UVR8
      regulated genes in maintaining photosynthetic competence was examined using
      mutants. Both F (v)/F(m) and Phi(PSII) decreased when plants were exposed to
      elevated UV-B, in general more so in uvr8 mutant plants than wild-type. UV-B
      increased the level of psbD-BLRP (blue light responsive promoter) transcripts,
      encoding the PSII D2 protein. This increase was mediated by the UVR8-regulated
      chloroplast RNA polymerase sigma factor SIG5, but SIG5 was not required to
      maintain photosynthetic efficiency at elevated UV-B. Levels of the D1 protein of
      PSII decreased markedly when plants were exposed to elevated UV-B, but there was
      no significant difference between wild-type and uvr8 under conditions where the
      mutant showed increased photoinhibition. The results show that UVR8 promotes
      photosynthetic efficiency at elevated levels of UV-B. Loss of the DI polypeptide
      is probably important in causing photoinhibition, but does not entirely explain
      the reduced photosynthetic efficiency of the uvr8 mutant compared to wild-type.

PMID- 23161228
TI  - Reactive oxygen and oxidative stress: N-formyl kynurenine in photosystem II and
      non-photosynthetic proteins.
AB  - While light is the essential driving force for photosynthetic carbon fixation,
      high light intensities are toxic to photosynthetic organisms. Prolonged exposure
      to high light results in damage to the photosynthetic membrane proteins and
      suboptimal activity, a phenomenon called photoinhibition. The primary target for
      inactivation is the photosystem II (PSII) reaction center. PSII catalyzes the
      light-induced oxidation of water at the oxygen-evolving complex. Reactive oxygen
      species (ROS) are generated under photoinhibitory conditions and induce oxidative
      post translational modifications of amino acid side chains. Specific modification
      of tryptophan residues to N-formylkynurenine (NFK) occurs in the CP43 and D1 core
      polypeptides of PSII. The NFK modification has also been detected in other
      proteins, such as mitochondrial respiratory enzymes, and is formed by a non
      random, ROS-targeted mechanism. NFK has been shown to accumulate in PSII during
      conditions of high light stress in vitro. This review provides a summary of what
      is known about the generation and function of NFK in PSII and other proteins.
      Currently, the role of ROS in photoinhibition is under debate. Furthermore, the
      triggers for the degradation and accelerated turnover of PSII subunits, which
      occur under high light, are not yet identified. Owing to its unique optical and
      Raman signal, NFK provides a new marker to use in the identification of ROS
      generation sites in PSII and other proteins. Also, the speculative hypothesis
      that NFK, and other oxidative modifications of tryptophan, play a role in the
      PSII damage and repair cycle is discussed. NFK may have a similar function during
      oxidative stress in other biologic systems.

PMID- 23161232
TI  - Lymphangiogenesis assessed using three methods is related to tumour grade, breast
      cancer subtype and expression of basal marker.
AB  - Lymphangiogenesis is a potential indicator of cancer patients' survival. However,
      there is no standardisation of methodologies applied to the assessment of
      lymphatic vessel density.  In 156 invasive ductal breast cancers (T ? 1/N+/M0),
      lymphatic and blood vessels were visualised using podoplanin and CD34,
      respectively. Based on these markers expression, four parameters were assessed:
      (i) distribution of podoplanin-stained vessels (DPV) - the percentage of fields
      with at least one lymphatic vessel (a simple method proposed by us), (ii)
      lymphatic vessel density (LVD), (iii) LVD to microvessel density ratio (LVD/MVD)
      and (iv) the expression of podoplanin in cancer-associated fibroblasts. Next, we
      estimated relations between the above-mentioned parameters and: (i) breast cancer
      subtype, (ii) tumour grade, and (iii) basal markers expression.  We found that
      intensive lymphangiogenesis, assessed using all studied methods, is positively
      related to high tumour grade, triple negative or HER2 subtype and expression of
      basal markers. Whereas, the absence of podoplanin expression in fibroblasts of
      cancer stroma is related to luminal A subtype, low tumour grade or lack of basal
      markers expression.  Distribution of podoplanin-stained vessels, assessed by a
      simple method proposed by us (indicating the percentage of fields with at least
      one lymphatic vessel), might be used instead of the "hot-spot" method.

PMID- 23161231
TI  - KRAS mutation testing in colorectal cancer as an example of the pathologist's
      role in personalized targeted therapy: a practical approach.
AB  - Identifying targets for personalized targeted therapy is the pathologist's domain
      and a treasure. For decades, pathologists have had to learn, understand, adopt
      and implement many new laboratory techniques as they arrived on the scene.
      Pathologists successfully integrate the results of those tests into final
      pathology reports that were, and still are, the basis of clinical therapeutic
      decisions. The molecular methods are different but no more difficult to
      comprehend in the era of "kit procedures". In recent years, the development of
      targeted therapies has influenced routine practices in pathology laboratories
      because the use of molecular techniques is required to include clinically useful
      predictive information in the pathology report. Pathologists have the knowledge
      and expertise to identify particular gene mutations using the appropriate
      molecular tests currently available.  This review focuses on the most important
      recent developments in KRAS mutation testing in metastatic colorectal cancer
      (CRC), and shows that a pathologist is involved in 10 stages of this procedure.
      Recent studies have shown that highly sensitive, simple, reliable and rapid
      assays may significantly improve the identification of CRC patients resistant to
      anti-EGFR therapy. Thus, direct sequencing does not seem to be an optimal
      procedure of KRAS testing for clinical purposes. Twelve currently available high
      sensitivity diagnostic assays (with the CE-IVD mark) for KRAS mutation testing
      are briefly described and compared. The suggested pathology report content for
      somatic mutation tests is described. In conclusion, evidence is presented that
      sending away paraffin blocks with tumor tissue for KRAS mutation testing may not
      be in the best interest of patients. Instead, an evidence-based approach
      indicates that KRAS mutation testing should be performed in pathology
      departments, only with the use of CE-IVD/FDA-approved KRAS tests, and with the
      obligatory, periodic participation in the KRAS EQA scheme organized by the
      European Society of Pathology as an independent international body.

PMID- 23161233
TI  - Histopathological analysis of chronic gastritis and correlation of pathological
      features with each other and with endoscopic findings.
AB  - Chronic gastritis is a very common disorder which is commonly caused by
      Helicobacter pylori. Histopathological examination is the mainstay of the
      diagnosis. We evaluated 300 gastric antral biopsies using revised Sydney system
      and concluded that it helps to analyse gastric biopsies in a very comprehensive
      manner. It was seen that H. pylori, chronic inflammatory infiltrate, neutrophilic
      infiltration, presence of lymphoid follicles and aggregates and surface
      epithelial damage are strongly associated with each other. The presence of one of
      these histological feature is a strong indicator for presence of other features.
      On the other hand intestinal metaplasia and atrophy of gastric glands was not
      associated with the above mentioned histological features. In the presence of
      dense chronic inflammation and infiltration by neutrophils one should carefully
      search for H. pylori organism. We also correlated histological features with
      endoscopy and found that cases of duodenal ulcer had more severe antral gastritis
      on histology as compared to those with hyperemia or antral erosions.

PMID- 23161234
TI  - Specificity and sensitivity of INI-1 labeling in epithelioid sarcoma. Loss of
      INI1 expression as a frequent immunohistochemical event in synovial sarcoma.
AB  - INI1 antigen is a product of the INI-1/SMARCB1 gene localized on chromosome 22q.
      It is well known that INI1 gene inactivation or loss of INI1 antigen expression
      is observed in epithelioid sarcomas; however, there are only few reports
      concerning specificity and sensitivity of immunohistochemical INI1 labeling as a
      marker of this neoplasm. That is why we decided to test 99 soft tissue sarcomas
      for the presence of the INI1 gene product. More specifically, the analyzed group
      consisted of 33 synovial sarcomas, 14 fibrosarcomas, 8 desmoid tumors, 8 DFSPs, 5
      MPNSTs, 9 epithelioid sarcomas, 11 Ewing sarcomas/PNETs, 9 rhabdomyosarcomas and
      2 clear cell sarcomas. Additionally, 7 malignant melanomas and 9 adenocarcinomas
      were included into the study.  Positive staining with an antibody against the INI
      1 gene product was observed in all studied cases of MPNST, Ewing sarcoma/PNET,
      rhabdomyosarcoma, malignant melanoma, clear cell sarcoma, and adenocarcinoma. On
      the contrary, none of 9 epithelioid sarcomas was labeled. The loss of INI1
      expression was also detected in 7 (21.2%) synovial sarcomas, confirmed
      cytogenetically or by FISH. Considering the lack of reaction with INI-1 antibody
      as a diagnostic test for epithelioid sarcoma we estimated that its sensitivity
      reached 100% and specificity - 83.5% (p < 0.0001).

PMID- 23161235
TI  - Pulmonary arteriovenous malformations in children and young adults.
AB  - Authors observed five cases of lung arteriovenous malformations in children and
      young adults. Clinical data and morphological pictures of these lesions were
      presented.

PMID- 23161236
TI  - Hobnail hemangioma: a immunohistochemical study and literature review.
AB  - Hobnail hemangioma is a rare vascular lesion with unusual morphology, including
      bland cells with hobnail appearance, a biphasic grow pattern with superficial
      dilated vessels and slit-like vessels in a deeper portion of the lesion and the
      infiltrative pattern of later growth, which may cause misdiagnosis. The
      differential diagnosis with hemangioendothelioma variants, low grade
      angiosarcomas and Kaposi sarcoma is of particular concern. The lack of
      recognition of this uncommon entity may result in excessive and unnecessary
      treatment. Immunohistochemistry stains play an important role in hobnail
      hemangioma differential diagnosis. Here, we present the results of our researches
      and also review of the literature as well as discussion about usage of
      immunohistochemistry in the diagnosis of HH.

PMID- 23161237
TI  - RAD51 gene polymorphisms and sporadic colorectal cancer risk in Poland.
AB  - BACKGROUND: DNA repair processes play an important role in protection against
      carcinogenic factors. Mutations in DNA repair genes, which code proteins engaged
      in repair processes, may lead to carcinogenesis and among others also to
      colorectal cancer (CRC) development. The genetic variability in RAD51 may
      contribute to the appearance and progression of various cancers including CRC.
      The aim of the study was to compare the distribution of genotypes of RAD51 135G>C
      and 172G>T polymorphism between colorectal cancer patients and controls. MATERIAL
      AND METHODS: Both polymorphisms were evaluated by PCR-RFLP methods in colorectal
      tissue of 320 colorectal cancer subjects and 320 healthy subjects who served as
      controls. RESULTS: In the present work we demonstrated a significant positive
      association between the RAD51 C/C genotype and colorectal carcinoma. Variant 135C
      allele of RAD51 increased the cancer risk. However, we did not observe any
      relationship between each polymorphism and colorectal cancer progression assessed
      by node metastasis, tumour size and Dukes' stage. CONCLUSIONS: Our results
      suggest that variant genotypes of the 135G>C of RAD51 polymorphism may be
      positively associated with colorectal carcinoma in the Polish population. Further
      studies conducted on a larger group are required to clarify this point.

PMID- 23161239
TI  - Primary myelolipoma of the lung: a case of report and review of literature.
AB  - Myelolipoma of the lung is a rare benign tumor composed of mature adipose tissue
      and normal hematopoietic cells. Only 8 cases of primary myelolipoma of the lung
      have been reported up to date. We report here the ninth case which was
      misdiagnosed as a malignant tumor and relevant literature is reviewed.

PMID- 23161238
TI  - Epithelioid angiosarcoma metastases to the bone marrow manifesting as
      erythroblastic anemia and leukocytosis: a case report and review of the
      literature.
AB  - Bone marrow is an exceptionally uncommon site of metastatic dissemination in
      angiosarcoma (AS) as only single case reports have been published so far. We
      report a case of a 72-year-old male with epithelioid angiosarcoma of the liver
      who subsequently developed erythroblastic anemia. The trephine bone marrow biopsy
      revealed total replacement of the normal hematopoiesis by diffuse infiltrate of
      AS. This rare complication of the clinical course of this tumor should be taken
      into account in the pathological diagnosis of patients with AS presenting with
      hematological abnormalities.

PMID- 23161241
TI  - Quiz. What is your diagnosis?

PMID- 23161240
TI  - Cellular angiofibroma with atypia or sarcomatous transformation - case
      description with literature review.
AB  - Cellular angiofibroma (CAF) is a rare, benign, mesenchymal tumor. It was first
      described by Nucci et al. in 1997 and then in 1998 by Laskin. The tumor occurs
      predominantly in the vulvo-vaginal or inguino-scrotal region. We present a 71
      year-old male, who was referred to the Bielanski Hospital with a three months'
      history of a slowly growing nodule in the right groin. Gross examination showed a
      well-circumscribed tumor attached to the spermatic cord and measuring 6 cm in the
      greatest dimension. Microscopic examination of the tumor showed a spindle cell
      lesion with a loose, myxoid, partly collagenized stroma with numerous, prominent
      thick-walled vessels. Scattered atypical cells were present.

PMID- 23161242
TI  - Chiral separation of beta-blockers by MEEKC using neutral microemulsion: Analysis
      of separation mechanism and further elucidation of resolution equation.
AB  - Based on the investigation of the effect of microemulsion charge on the chiral
      separation, a new chiral separation method with MEEKC employing neutral
      microemulsion was established. The method used a microemulsion containing 3.0%
      (w/v) neutral surfactant Tween 20 and 0.8% (w/v, 30 mM) dibutyl l-tartrate in 40
      mM sodium tetraborate buffer to separate the enantiomers of beta-blockers. The
      effect of major parameters on the chiral separation was investigated. The applied
      voltage had little effect on the resolution, but the chiral separation could be
      improved by suppressing the EOF. Nine racemic beta-blockers obtained relatively
      good enantioseparation after appropriate concentrations of tetradecyl trimethyl
      ammonium bromide were added into the microemulsion to suppress the EOF. These
      results were explained based on the analysis of the separation mechanism of the
      method and deduced separation equations. The resolution equation of the method
      was further elucidated. It was found that the fourth term in the resolution
      equation, an additional term compared to the conventional resolution equation for
      column chromatography, represents the ratio of the relative movement distance
      between the analyte and microemulsion droplets relative to the effective
      capillary length. It can be regarded as a correction for the effective capillary
      length. These findings are significant for the development of the theory of MEEKC
      and the development of new chiral MEEKC method.

PMID- 23161250
TI  - Advance in research of microRNA in Caenorhabditis elegans.
AB  - microRNA (miRNA) is a family of small, non-coding RNA first discovered as an
      important regulator of development in Caenorhabditis elegans (C. elegans).
      Numerous miRNAs have been found in C. elegans, and some of them are well
      conserved in many organisms. Though, the biologic function of miRNAs in C.
      elegans was largely unknown, more and more studies support the idea that miRNA is
      an important molecular for C. elegans. In this review, we revisit the research
      progress of miRNAs in C. elegans related with development, aging, cancer, and
      neurodegenerative diseases and compared the function of miRNAs between C. elegans
      and human.

PMID- 23161251
TI  - Effects of logged and unlogged forest patches on avifaunal diversity.
AB  - In the Hyrcanian forests of northern Iran, reduced-impact silviculture systems,
      (single-tree and group-tree selection) were applied over a large area, which
      generated different local habitat structures. The aim of this study was to assess
      the differences between treated and untreated areas of forest and their effect on
      avian richness, abundance and diversity (R.A.D). Birds were surveyed during the
      breeding season in 2009 by 100-point counts, equally distributed in the treated
      and untreated area. Avian R.A.D was significantly different and higher in the
      untreated area. Generally, forestry practices cause noticeable changes in canopy
      percentage, tree composition, snags and shrub number. Treated forest habitats in
      the area of study had a much more developed understory, fewer snags and fewer
      large diameter trees. The results highlighted the importance of forest maturity
      and showed that preventing silvicultural disturbances may not be the best
      solution for conserving and enhancing biodiversity. Rather, methods such as
      selective cutting seem an appropriate and sustainable way of forest management.
      It is suggested that forests should be managed to conserve structural elements
      which create favorable habitat for bird species, preventing future species losses
      due to logging practices.

PMID- 23161252
TI  - Improving conservation of Florida manatees (Trichechus manatus latirostris):
      conceptualization and contributions toward a regional warm-water network
      management strategy for sustainable winter habitat.
AB  - We used southwestern Florida as a case study to lay the groundwork for an
      intended and organized decision-making process for managing warm-water habitat
      needed by endangered manatees to survive winters in Florida. Scientists and
      managers have prioritized (a) projecting how the network of warm-water sites will
      change over the next 50 years as warmed industrial discharges may expire and as
      flows of natural springs are reduced through redirection of water for human uses,
      and (b) mitigating such changes to prevent undue consequences to manatees. Given
      the complexities introduced by manatee ecology; agency organizational structure;
      shifting public demands; fluctuating resource availability; and managing within
      interacting cultural, social, political, and environmental contexts, it was clear
      that a structured decision process was needed. To help promote such a process, we
      collected information relevant to future decisions including maps of known and
      suspected warm-water sites and prototyped a characterization of sites and
      networks. We propose steps that would lead to models that might serve as core
      tools in manatee/warm-water decision-making, and we summarized topics relevant
      for informed decision-making (e.g., manatee spatial cognition, risk of cold
      stress morbidity and mortality, and human dimensions). A major impetus behind
      this effort is to ensure proactively that robust modeling tools are available
      well in advance of the anticipated need for a critical management decision.

PMID- 23161253
TI  - Snail darters and sacred places: creative application of the endangered species
      act.
AB  - Rather than exploring how indigenous people have been alienated from resources by
      environmental policies, this paper explores how indigenous peoples have worked
      with environmental organizations to use the broad protections provided by
      environmental laws to protect cultural resources. The Eastern Band of Cherokee
      Indians, along with other concerned groups, partnered with environmentalists in
      opposing the destruction of the endangered snail darter's critical habitat by the
      Tennessee Valley Authority's Tellico Dam. The dam had been opposed by a shifting
      alliance of Cherokees, local farmers, trout fisherman, and environmentalists
      since it was announced in 1963. A previous lawsuit by this coalition delayed the
      project from 1972 to 1974 under the National Environmental Policy Act. The
      Endangered Species Act provided this coalition with a powerful tool for opposing
      the destruction of burial grounds and sacred village sites throughout the lower
      Little Tennessee River valley. The coalition of environmental organizations,
      Cherokees, and others was ultimately unsuccessful in stopping the dam from being
      built, but was successful in establishing a strict precedent for the enforcement
      of the Endangered Species Act. The lawsuit also created a space for the Eastern
      Band to negotiate for the return of Cherokee remains and halt the removal of any
      additional burials. In this situation, the strategic support of environmental
      regulation enabled the Eastern Band to exert some degree of control over the fate
      of cultural resources in the valley, and also demonstrates the significant role
      American Indian peoples played in one of the seminal events of the environmental
      movement during the 1970s. 

PMID- 23161254
TI  - Finding a pathological diagnosis for Alzheimer's disease: are inflammatory
      molecules the answer?
AB  - Conventional diagnostic tools for Alzheimer's disease (AD) are currently based on
      a number of clinical criteria, and a definitive diagnosis still relies on
      pathological evaluation at autopsy. Moreover, neurodegenerative changes are
      believed to begin years before clinical presentation. There is therefore an
      essential need for a reliable AD biomarker to aid in the identification of
      preclinical disease, early diagnosis, prediction of disease progression and
      treatment response. There is mounting evidence that chronic inflammatory
      processes play a fundamental role in the progression of neuropathological changes
      in AD. Clinical and experimental evidence supports the involvement of
      inflammatory changes in the early stages of AD, even before the appearance of
      amyloid deposits. Therefore biomarkers that reflect the inflammatory process in
      AD hold promise. Tests based on these should preferably be reliable, noninvasive
      and costeffective, which has led to an increasing focus on the use of blood-based
      biomarkers. This review considers the current progress in AD inflammatory
      biomarker research followed by a detailed analysis of two leading putative
      inflammatory biomarkers: alpha-2-macroglobulin and clusterin.

PMID- 23161255
TI  - Neuropsychological features of patients with Parkinson's disease and impulse
      control disorders.
AB  - Impulse control disorders (ICDs) are frequent in Parkinson's disease (PD). Aim of
      the present study was to investigate cognition and behaviour in PD patients with
      and without ICDs, in order to identify potential early clinical features which
      might be associated to the development of ICDs. We recruited 17 PD patients with
      ICDs and 17 without ICDs, matched for several clinical variables, without
      clinically significant cognitive deficits. Assessments included behavioural
      scales and a neuropsychological battery, including the Iowa Gambling Task (IGT).
      In patients with ICDs, the total score of the BIS and the Motor Impulsivity
      subscore were significantly higher than in patients without ICDs. In patients
      with ICDs, we observed only statistical trends towards a worse performance on
      neuropsychological tasks (go-no-go subtest of the Frontal Assessment Battery,
      oral verb naming task, copying of drawings with landmarks) sensitive to frontal
      lobe dysfunction (FLD) and on the IGT (loss of a greater amount of money, more
      risky choices). As compared to patients without ICDs, they reported a more than
      threefold number of errors on the interference subtest of Stroop test, which is
      also sensitive to FLD. Although this study did not show any significant
      difference between PD patients presenting ICDs as compared with patients without
      ICDs on neuropsychological variables, some preliminary evidence was detected
      suggesting a trend toward a worse performance of the PD-ICD group on few
      neuropsychological tasks which are at least partially sensitive to frontal lobe
      dysfunction, including tasks sensitive to dysfunction of ventral fronto-striatal
      loops. 

PMID- 23161256
TI  - Updating on Italian stroke units: the "CCM study".
AB  - The stroke units (SUs) have been demonstrated to be efficient and cost effective
      for acute stroke care. Nevertheless, the level of stroke unit implementation in
      Italy does not correspond to expectations yet. This study is a survey, which aims
      at assessing the current status of in-hospital stroke care in the Italian regions
      and at updating SUs. The survey was conducted by means of a semi-structured
      questionnaire, based on 18 stroke care "quality indicators", submitted to all the
      Italian centres that had taken part in the SITS-MOST study, and to other centres
      advised by the coordinator of SITS studies and by regional opinion leaders of
      stroke. SUs were defined as acute wards, with stroke-dedicated beds and dedicated
      teams that had been formally authorised to administer rt-PA. A statistical
      analysis was performed by a descriptive statistics and logistic regression model.
      The study was carried out from November 2009 to September 2010. A total of 168
      forms were sent out and 153 replies received. Seven centres, which had not
      performed any thrombolytic treatment, and 16 which did not fulfil the criteria
      for the definition of SU were excluded from the study. Most of the centres
      reported more than 100 stroke patient admissions per year, i.e., 122 (84%) from
      100 to 500, 18 (12%) more than 500. The 19% of the centres admitted more than 30%
      of patients within 3 h from the symptom onset and only 30% admitted more than 30%
      of patients within 4.5 h. The mean number of thrombolyses performed in the last 6
      months was 10 for centres with a doctor on duty 24 h a day, 6 for those that have
      a doctor on duty from 8 a.m. to 8 p.m. and a doctor on call for night, and 5 for
      centres with a doctor on call 24 h a day. The territorial distribution of the SUs
      is remarkably heterogeneous: 87 SUs (67%) are located in the North of Italy, 28
      (22%) in the central part of Italy and only 15 (11%) in the South. The last few
      years have witnessed a rise in both the diffusion of SUs and access to
      thrombolytic therapy in Italy. Despite this, there are a few large areas, mostly
      in the south, where the requirements of healthcare legislation are not met, and
      access to a dedicated SU and thrombolytic treatment is still limited and poor.

PMID- 23161257
TI  - Progress and prospects in neurorehabilitation: clinical applications of stem
      cells and brain-computer interface for spinal cord lesions.
AB  - Spinal cord injury (SCI) is a disease that affects millions of people worldwide,
      causing a temporary or permanent impairment of neuromotor functions. Mostly
      associated to traumatic lesions, but also to other forms of disease, the
      appropriate treatment is still unsure. In this review, several ongoing studies
      are presented that aim to provide methods of prevention that ensure quality of
      life, and rehabilitation trends to patients who suffer from this injury. Stem
      cell research, highlighted in this review, seeks to reduce damage caused to the
      tissue, as also provide spinal cord regeneration through the application of
      several types of stem cells. On the other hand, research using brain-computer
      interface (BCI) technology proposes the development of interfaces based on the
      interaction of neural networks with artificial tools to restore motor control and
      full mobility of the injured area. PubMed, MEDLINE and SciELO data basis analyses
      were performed to identify studies published from 2000 to date, which describe
      the link between SCI with stem cells and BCI technology.

PMID- 23161258
TI  - A possible case of Hashimoto's encephalopathy after surgery and radiometabolic
      therapy for thyroid carcinoma.

PMID- 23161259
TI  - Trail Making Test error analysis in classic motor neuron disease.
AB  - The use of non-traditional scores in neuropsychological assessment allows for
      pattern analysis of test performance, commonly referred to as Quantified Process
      Approach (QPA). In the present study, the QPA was taken to study error rates on
      the Trail Making Test (TMT) in 26 non-demented patients with classic motor neuron
      disease (cMND), who commonly present with impaired cognitive flexibility, and 26
      matched healthy controls. Between-group comparisons revealed that cMND patients
      exhibited higher total error rates on the TMT Part B (TMT-B) relative to controls
      (p < 0.001), though no significant associations were noted between TMT errors and
      measures of attention and executive function obtained using the Stroop
      Neuropsychological Screening Test, the Wechsler Adult Intelligence Scale Digit
      Symbol and Digit Span subtests and the Wisconsin Card Sorting Test. Moreover, the
      percentage of cMND patients with normal TMT-B time-to-completion who committed at
      least one error (either sequential or perseverative errors) in TMT-B was
      significantly higher compared to controls (p = 0.005). These findings suggest
      that error analysis using the QPA may increase the clinical utility of TMT and
      should be considered in addition to time-to-completion scores, in the
      neuropsychological assessment of patients with cMND.

PMID- 23161260
TI  - Understanding quantitative and qualitative figural fluency in patients with
      Parkinson's disease.
AB  - Figural fluency refers to the ability to internally generate appropriate non
      verbal behaviour. Whereas deficits in verbal fluency rank among the most
      prominent cognitive sequelae in Parkinson's disease (PD), little is known about
      figural fluency and its assessment in PD. This is the first comprehensive
      comparison of the psychometric properties of figural fluency tasks in PD. PD
      patients (n = 22) and matched normal controls (n = 27) were compared in widely
      used figural fluency measures. The ability to assess PD-specific cognitive
      morbidity was assessed via comparison with a matched neurological sample of
      various aetiologies (n = 22). Construct validity was assessed by means of linear
      regression analyses of figural fluency measures and an extensive cognitive test
      battery. PD patients were impaired in all measures of figural fluency tasks. PD
      specific impairments were identified regarding perseverative and strategic
      behaviour. Importantly, only perseverative, but not repetitive, behaviour was
      able to identify PD-specific cognitive morbidity. Quantitative fluency can be
      predicted by basic cognitive functions (e.g. visuospatial ability, visuomotor
      speed) as well as other measures of executive functioning. However, qualitative
      test scores, especially of the Five-Point Test (FPT), yield important and
      additional diagnostic information in PD. Qualitative test parameters of figural
      fluency measures, especially of the FPT, offer the unique possibility to assess
      PD-specific cognitive impairments in the areas of perseverative and strategic
      behaviour.

PMID- 23161262
TI  - Prescottia equi gen. nov., comb. nov.: a new home for an old pathogen.
AB  - The taxonomic status of Rhodococcus equi, originally isolated from foal
      specimens, has been the subject of discussion for a number of years. The
      chequered history of the taxon has prompted this polyphasic analysis of R. equi
      strains, close members of the genus Rhodococcus and representatives of other
      genera classified in the order Corynebacteriales, to establish the taxonomic
      position of this taxon. Thirty one R. equi strains, including the type strain,
      were examined for genotypic and numerical taxonomic properties. The resultant
      data are consistent with their classification in the order Corynebacteriales but
      the R. equi strains formed a distinct phyletic clade away from representatives of
      other members of the genus Rhodococcus in the 16S rRNA gene tree. Representatives
      of this clade shared their highest pairwise 16S rRNA gene sequence similarities
      with the type strain of Rhodococcus kunmingensis (95.2-98.1 %). However, the R.
      equi taxon was readily distinguished from R. kunmingensis and from the other
      members of the order Corynebacteriales using a combination of genotypic,
      chemotypic and phenotypic properties. On the basis of these data the R. equi
      strains are considered to represent a new genus. The name proposed for this taxon
      is Prescottia gen. nov., with Prescottia equi comb. nov. as the type species
      containing the type strain, C 7(T) (= ATCC 25729(T) = ATCC 6939(T) = CCUG 892(T)
      = CIP 54.72(T) = DSM 20307(T) = HAMBI 2061(T) = NBRC 14956(T) = JCM 1311(T) = JCM
      3209(T) = LMG 18452(T) = NBRC 101255(T) = NCTC 1621(T) = NRRL B-16538(T) = VKM Ac
      953(T)).

PMID- 23161263
TI  - Position of the conus medullaris in fetuses with skeletal dysplasia.
AB  - OBJECTIVES: To examine whether reduced conus distance (CD) measurement may be a
      marker for impaired growth of the fetal trunk in fetuses with certain types of
      skeletal dysplasia. METHODS: Two hundred fifty-four normal cases and 24
      pregnancies with skeletal dysplasia were included. The fetuses with skeletal
      dysplasia were subdivided into two groups based on the specific diagnosis:
      skeletal dysplasias with a short trunk and skeletal dysplasias with a normal size
      trunk. Linear regression analysis was used to examine the relationship of the CD
      measurement with the biparietal diameter. CD measurements in the two groups of
      fetuses with skeletal dysplasia were compared using z-scores. RESULTS: In fetuses
      with skeletal dysplasia and shortened trunk, the CD measurement was significantly
      smaller than in the normal population (mean z-score -3.7, p < 0.0001). CD
      measurements in fetuses with skeletal dysplasia but a normal trunk size were
      similar to the normal population (mean z-score -0.1, p = 0.997). CONCLUSIONS:
      Short CD is associated with certain types of skeletal dysplasia. As such,
      measuring the CD may be helpful in diagnosing these conditions.

PMID- 23161264
TI  - Competition of thermodynamic and dynamic factors during formation of
      multicomponent particles via spray drying.
AB  - As psicose cannot be spray dried because of its low glass transition temperature
      (T(g)), additives have been used to manufacture spray-dried particles. Its
      thermodynamic miscibility with each additive was evaluated by thermal analysis
      and C solid-state nuclear magnetic resonance. Aspartame was miscible with psicose
      at all ratios, and spray-dried particles were obtained when T(g) of the mixture
      was higher than the outlet temperature of the spray dryer, where 30 wt % of
      psicose was loaded. poly(vinylpyrrolidone) and cluster dextrin were partially
      miscible with psicose, with a maximum loading of 40 wt %. When polymeric
      excipients were used, their mixing behavior with psicose was affected by the
      dynamic factor during the spray drying, that is, enhanced phase separation due to
      the molecular-weight difference. The T(g) value of the polymer-rich phases, which
      were likely to form shell layers on the surfaces, played an important role in
      determining availability of the spray-dried particles. Hydroxypropyl
      methylcellulose (HPMC) offered a very effective loading capacity of 80 wt %, due
      to distinct phase separation to form shell phase with a very high T(g). Because
      molecular weight of HPMC was the smallest among the polymeric excipients, the
      thermodynamic miscibility seemed to affect the dynamic phase separation. These
      results provide useful information for preparing multicomponent spray-dried
      particles.

PMID- 23161265
TI  - A complete serial compound temporal difference simulator for compound stimuli,
      configural cues and context representation.

PMID- 23161267
TI  - Cholangiopancreatoscopy and endoscopic ultrasound for indeterminate
      pancreaticobiliary pathology.
AB  - BACKGROUND: Techniques to confirm suspected pancreaticobiliary (PB) malignancy
      when index sampling is non-diagnostic include cholangiopancreatoscopy (CP) and
      endoscopic ultrasound (EUS). However, comparative data are lacking. AIM: The
      purpose of this study was to compare the yield of EUS and CP for the diagnosis of
      PB pathology. METHODS: Consecutive patients with indeterminate PB pathology who
      underwent both CP and EUS within 3 months of each other were retrospectively
      identified. For CP, tissue sampling included biopsy under direct inspection
      (cholangioscopy-directed biopsy), biopsy following CP with fluoroscopic guidance
      (cholangioscopy-assisted biopsy), or brush cytology. For EUS-FNA, lesions
      included ductal strictures or hypoechoic masses. A comparison of operating
      characteristics between CP and EUS utilizing tissue confirmation or 12-month
      clinical course consistent with either benign or malignant disease was performed.
      RESULTS: Between February 2000 and June 2007, 66 (33 males, 33 females, median
      age 64.5) patients with indeterminate PB pathology who had undergone both CP and
      EUS within 3 months of each other were included. Lesions amenable to sampling
      were noted in 59 CP and 50 EUS patients. On follow-up, 39 patients had neoplasia
      and 27 were benign. The sensitivity/specificity for the diagnosis of neoplasia
      for CP and EUS was 48.7/96.3 % and 33.3/96.3 %, respectively (comparison of
      sensitivities, P = 0.183). The combined (CP and EUS) sensitivity/specificity was
      66.7/96.3 % (P = 0.0064 and P = 0.0001 comparing combined sensitivity vs.
      sensitivity of either CP alone or EUS alone, respectively). CONCLUSIONS: In
      patients who undergo both EUS and CP for indeterminate PB pathology, the combined
      yield of EUS and CP to detect neoplasia appears to be higher than either
      examination alone.

PMID- 23161266
TI  - Association between housing quality and individual health characteristics on
      sleep quality among Latino farmworkers.
AB  - Although poor sleep quality and associated sleep disorders are associated with
      increased risk of job injury and multiple mental and physical health problems,
      scant research has examined sleep quality among Latino farmworkers. Interviews
      were conducted with 371 male Latino farmworkers working in North Carolina during
      the 2010 agricultural season. Data on housing quality and sleep quality were
      collected. Access to air conditioning was significantly and positively associated
      with good sleep quality. This association remained when other housing
      characteristics and individual health indicators were controlled. Good sleep
      quality was associated with low levels of pain, depression, and anxiety. Poor
      sleep quality among Latino farmworkers was associated with poorer indicators of
      health. One important indicator of housing quality, air conditioning, was
      associated with better sleep quality. Further research is required to delineate
      how to improve the adequacy of farmworker housing to improve sleep quality and
      other health indicators. 

PMID- 23161268
TI  - Orally administered phosphatidic acids and lysophosphatidic acids ameliorate
      aspirin-induced stomach mucosal injury in mice.
AB  - BACKGROUND: Recent investigations revealed that lysophosphatidic acid (LPA), a
      phospholipid with a growth factor-like activity, plays an important role in the
      integrity of the gastrointestinal tract epithelium. AIM: This paper attempts to
      clarify the effect of orally administered phosphatidic acid (PA) and LPA on
      aspirin-induced gastric lesions in mice. MATERIALS AND METHODS: Phospholipids, a
      free fatty acid, a diacylglycerol and a triglyceride at 1 mM (5.7 MUmol/kg body
      weight) or 0.1 mM were orally administered to mice 0.5 h before oral
      administration of aspirin (1.7 mmol/kg). The total length of lesions formed on
      the stomach wall was measured as a lesion index. Formation of LPA from PA in the
      mouse stomach was examined by in vitro (in stomach lavage fluid), ex vivo (in an
      isolated stomach) and in vivo (in the stomach of a living mouse) examinations of
      phospholipase activity. RESULTS: Palmitic acid, dioleoyl-glycerol, olive oil and
      lysophosphatidylcholine did not affect the aspirin-induced lesions. In contrast,
      phosphatidylcholine (1 mM), LPA (1 mM) and PA (0.1, 1 mM) significantly reduced
      the lesion index. Evidence for formation of LPA from PA in the stomach by gastric
      phospholipase A2 was obtained by in vitro, ex vivo and in vivo experiments. An
      LPA-specific receptor, LPA2, was found to be localized on the gastric surface
      lining cells of mice. CONCLUSION: Pretreatment with PA-rich diets may prevent
      nonsteroidal anti-inflammatory drug-induced stomach ulcers.

PMID- 23161269
TI  - Gel electrophoresis of a charge-regulated, bi-functional particle.
AB  - Adopting a Brinkman fluid model, we analyzed the electrophoresis of a charged
      regulated, bi-functional particle containing both acidic and basic functional
      groups in a gel solution. Both the long-range hydrodynamic effect arising from
      the liquid drag and the short-range steric effect from particle-polymer
      interaction are considered. The type of particle considered is capable of
      simulating both biocolloids such as microorganisms and cells, and particles with
      adsorbed polyelectrolyte or membrane layer. Our model describes successfully the
      experimental data in the literature. The presence of gel has the effect of
      reducing the particle mobility and alleviating double-layer polarization so that
      the particle behavior is less complicated than that in the case where gel is
      absent. On the other hand, both the quantitative and qualitative behaviors of a
      particle depend highly on solution pH and background salt concentration, yielding
      interesting and significant results. These results provide valuable information
      for both experimental data interpretation and electrophoresis devices design.

PMID- 23161270
TI  - Changes in concentration of Alternaria and Cladosporium spores during summer
      storms.
AB  - Fungal spores are known to cause allergic sensitization. Recent studies reported
      a strong association between asthma symptoms and thunderstorms that could be
      explained by an increase in airborne fungal spore concentrations. Just before and
      during thunderstorms the values of meteorological parameters rapidly change.
      Therefore, the goal of this study was to create a predictive model for hourly
      concentrations of atmospheric Alternaria and Cladosporium spores on days with
      summer storms in Szczecin (Poland) based on meteorological conditions. For this
      study we have chosen all days of June, July and August (2004-2009) with
      convective thunderstorms. There were statistically significant relationships
      between spore concentration and meteorological parameters: positive for air
      temperature and ozone content while negative for relative humidity. In general,
      before a thunderstorm, air temperature and ozone concentration increased, which
      was accompanied by a considerable increase in spore concentration. During and
      after a storm, relative humidity increased while both air temperature ozone
      concentration along with spore concentrations decreased. Artificial neural
      networks (ANN) were used to assess forecasting possibilities. Good performance of
      ANN models in this study suggest that it is possible to predict spore
      concentrations from meteorological variables 2 h in advance and, thus, warn
      people with spore-related asthma symptoms about the increasing abundance of
      airborne fungi on days with storms. 

PMID- 23161271
TI  - A study on the physical fitness index, heart rate and blood pressure in different
      phases of lunar month on male human subjects.
AB  - The gravitational pull of the moon on the earth is not the same in all phases of
      the lunar month, i.e. new moon (NM), first quarter (FQ), full moon (FM) and third
      quarter (TQ), and as a result the amplitude of tide differs in different phases.
      The gravitational pull of the moon may have effects on the fluid compartments of
      the human body and hence the cardiovascular system may be affected differentially
      in the different phases of the lunar month. In the present study resting heart
      rate (HR) and blood pressure (BP), physical fitness index (PFI), peak HR and BP
      immediately after step test, and recovery HR and BP after step test were measured
      during different phases of the lunar month in 76 male university students (age
      23.7 +/- 1.7 years). At rest, both systolic and mean arterial BP were ~5 mmHg
      lower in NM and FM compared to FQ and TQ, but resting HR was not significantly
      different between phases. Further, peak HR and peak systolic BP after step test
      were lower (~4 beat/min and ~5 mmHg, respectively) in NM and FM compared to FQ
      and TQ. PFI was also higher (~5) in NM and FM compared to FQ and TQ. Recovery of
      HR after step test was quicker in NM and FM compared to that of FQ and TQ. It
      appears from this study that gravitational pull of the moon may affect the
      cardiovascular functions of the human body. Moreover, the physical efficiency of
      humans is increased in NM and FM due to these altered cardiovascular regulations.

PMID- 23161272
TI  - Effects of different feeding time and frequency on metabolic conditions and milk
      production in heat-stressed dairy cows.
AB  - The aim of this paper was to evaluate the effects of three different feeding
      management (FM) schedules on physiological markers of heat stress (HS), metabolic
      conditions, milk yield and quality during the hot season in dairy cows. The study
      involved 27 mid-lactating cows, subdivided in three homogeneous groups differing
      in feeding time and frequency: total mixed ration (TMR) delivered once daily in
      the morning (M); twice daily, half in the morning and half in the evening (ME);
      once daily in the evening (E). During the trial, blood samples were collected in
      the morning (a.m.) and in the evening (p.m.), breathing rate (BR), rectal
      temperature (RT), and milk yield were recorded and individual milk samples were
      collected. Microclimate data indicated that cows were subjected to mild-moderate
      HS. During the hotter days, cows receiving M treatment showed higher values of RT
      (38.97  degrees C vs 38.68  degrees C and 38.62  degrees C, in ME and E) and BR
      (71.44 vs 66.52 and 65.26 breaths min-1, in ME and E), a.m. plasma glucose was
      lower in M (3.69 vs 3.83 and 3.83 mmol L-1, in ME and E) and a.m. plasma urea was
      lower in E (4.82 vs 5.48 and 5.35 mmol L-1, in M and ME). Milk yield was
      unaffected by FM, as well as milk composition and cheese-making properties. Only
      milk protein content and yield were higher in M (3.42 vs 3.36 and 3.27 g 100 mL
      1; and 1.11 vs 1.08 and 1.02 kg day-1, for ME and E). Our results on cow
      physiology indicate that M seems a less suitable FM to match cow welfare during
      the summer season.

PMID- 23161274
TI  - Protective effect of thymoquinone against cisplatin-induced ototoxicity.
AB  - The aim of this study was to investigate the potential protective effect of
      thymoquinone against cisplatin-induced ototoxicity. This study is a prospective,
      controlled experimental animal study. Experiments were performed on 30 healthy
      female Sprague-Dawley rats. Thirty animals were divided into three groups of 10
      animals each. Group 1 received an intraperitoneal (i.p.) injection of cisplatin
      15 mg/kg. Group 2 received i.p. thymoquinone 40 mg/kg/day for 2 days prior to
      cisplatin injection and third day i.p. cisplatin 15 mg/kg was administered
      concomitantly. Group 2 continued to receive i.p. thymoquinone until fifth day.
      Group 3 received i.p. thymoquinone 40 mg/kg/day for 5 days. Pretreatment
      distortion product otoacoustic emissions (DPOAE) and auditory brain stem
      responses (ABR) testing from both ears were obtained from the animals in all
      groups. After the baseline measurements, drugs were injected intraperitonally.
      After an observation period of 3 days, DPOAE measurements and ABR testing were
      obtained again and compared with the pretreatment values. There was no
      statistically significant difference between pre and post-treatment DPOAE
      responses and ABR thresholds group 2 and 3. However, group 1 demonstrated
      significant deterioration of the ABR thresholds and DPOAE responses. Our results
      suggest that DPOAE responses and ABR thresholds were preserved in the cisplatin
      plus TQ-treated group when compared with the group receiving cisplatin alone.
      According to these results, cisplatin-induced ototoxicity may be prevented by
      thymoquinone use in rats.

PMID- 23161275
TI  - Multicenter evaluation of Neurelec Digisonic(r) SP cochlear implant reliability.
AB  - Over the past decade, the adoption of universal hearing screening in newborns has
      led to earlier detection of hearing problems and significant lowering of the age
      of first cochlear implantation. As a consequence, recipients are now expected to
      keep their cochlear implants (CIs) for a longer period of time. Comprehensive
      longitudinal information on CI reliability is essential for device choice. The
      aim of this study was to assess the reliability (in children and adults) of the
      latest generation of the Digisonic((r)) SP CI launched in 2006 by Neurelec.
      Failure rate (FR) and cumulative survival rate (CSR) for a 5-year period were
      calculated. This survey is a multicenter retrospective study. A questionnaire was
      sent to nine CI centers requesting information about patients implanted with
      Neurelec Digisonic((r)) SP CIs. FR and CSR over a 5-year period were calculated
      on this group. Collaborating centers collected data on 672 patients (362 children
      and 310 adults) implanted between March 2006 and March 2011. The overall rate of
      explantation was 2.23 % (15 cases): six devices were explanted due to device
      failure (0.89 %) and nine were explanted for medical reasons (1.34 %). Four
      patients were lost to follow-up. The CSR at 5 years was 98.51 % on all patients,
      98.48 % for children and 98.57 % for adults. FR was 0.97 % for adults and 0.83 %
      for children. This first independent study that assesses FR and CSR on the
      current generation of Digisonic((r)) SP CI represents an important resource that
      can help clinicians and patients during their device choice.

PMID- 23161276
TI  - 3D images based on MDCT in evaluation of patients with suspected foreign body
      aspiration.
AB  - To evaluate the value of 3D images based on multi-detect computer tomography
      (MDCT) for the diagnosis and management of patients with suspected foreign bodies
      aspiration, and report our experience about diagnosis and management of the
      aforementioned patients using the 3D images, as well as detail our protocol for
      the management of those patients. Forty-four patients (37 children, 7 adults)
      with suspected foreign bodies aspiration who accepted pre-surgical examination
      and bronchoscopy in our hospital were included in this study. All the patients'
      pre-surgical 3D images based on MDCT were reconstructed and analyzed. After that
      all the results were compared with observations in the surgeries. Among the 37
      pediatrics, 34 patients were detected with FB in their tracheobronchial system by
      the 3D images based on MDCT, and 3 cases were detected negative. The sensitivity
      of 3D images is 100 %, and the specificity is 75 %.In the adult group, all the 7
      cases of FB in the tracheobronchial tree were detected by 3D images and proved by
      bronchoscopy. 3D images based on MDCT were proved to be a valuable method for the
      diagnosis of the patients with suspected FB aspiration. In the diagnosis and
      management of those patients, we considered that both the typical FB aspiration
      history and the intractable symptoms of cough should be taken as the criteria and
      the first step for selecting those suspected patients; then 3D images based on
      MDCT could be taken as the second step and as the selective criteria for those
      patients who should accept the rigid bronchoscopy.

PMID- 23161277
TI  - Cytotoxic effect of natural trans-resveratrol obtained from elicited Vitis
      vinifera cell cultures on three cancer cell lines.
AB  - trans-Resveratrol (trans-R) has been reported to be a potential cancer
      chemopreventive agent. Although its cytotoxic activity against different cancer
      cell lines has been tested, its effect on human acute leukemia cell lines has
      scarcely been investigated, and only a few in vitro studies were performed using
      human breast epithelial cell lines. Due to its potential value for human health,
      demand for trans-R has rapidly increased, and new biotechnological strategies to
      obtain it from natural edible sources have been developed. Thus, grapevine cell
      cultures represent a reliable system of trans-R production since they
      biosynthesize trans-R constitutively or in response to elicitation. In addition,
      there are no studies deepen on the inhibitory effect of trans-R, produced by
      elicited grapevine cell cultures, on growth of human tumor cell lines. In this
      work, the effect of trans-R extracted from the culture medium, after elicitation
      of grapevine cell cultures, was tested on two human acute lymphocytic and
      monocytic leukemia cell lines, and one human breast cancer cell line. The effect
      of trans-R on cell proliferation was not only dose- and time-dependent but also
      cell type-dependent, as seen from the different degrees of susceptibility of
      cancer cell lines tested. As regards the effect of trans-R on cell cycle
      distribution, low trans-R concentrations increased cells in the S phase whereas a
      high trans-R concentration increased G0/G1 phase in all cell lines. Perturbation
      of the cell cycle at low trans-R concentrations did not correlate with the
      induction of cell death, whereas a high trans-R concentration, cell proliferation
      decreased as a result of increasing apoptosis in the three cell lines. In
      leukemia cells, trans-R up-regulated the expression of caspase-3 while trans-R
      induced apoptosis in breast cells occur through a caspase-3-independent mechanism
      mediated by a down-regulation of Bcl-2.

PMID- 23161278
TI  - A simple and rapid fluorescence in situ hybridization microwave protocol for
      reliable dicentric chromosome analysis.
AB  - Fluorescence in situhybridization (FISH) is an extremely effective and sensitive
      approach to analyzing chromosome aberrations. Until recently, this procedure has
      taken multiple days to complete. The introduction of telomeric and centromeric
      peptide nucleic acid (PNA) probes has reduced the procedure's duration to several
      hours, but the protocols still call for a high temperature (80-90 degrees C) step
      followed by 1-3 h of hybridization. The newest method to speed up the FISH
      protocol is the use of a microwave to shorten the heating element to less than a
      minute; however this protocol still calls for a 1-h hybridization period. We have
      utilized PNA centromere/telomere probes in conjunction with a microwave oven to
      show telomere and centromere staining in as little as 30 s. We have optimized the
      hybridization conditions to increase the sensitivity and effectiveness of the new
      protocol and can effectively stain chromosomes in 2 min and 30 s of incubation.
      We have found that our new approach to FISH produces extremely clear and distinct
      signals. Radiation-induced dicentric formation in mouse and human fibroblast
      cells was analyzed by two individual scorers and the observed dicentrics matched
      very well.

PMID- 23161279
TI  - Contactless conductivity detection for analytical techniques: developments from
      2010 to 2012.
AB  - The developments in the field of capacitively coupled contactless conductivity
      detection in the approximate period from July 2010 to June 2012 are traced. Few
      reports concerning fundamental studies or new detector designs have appeared. On
      the other hand, applications in standard CZE are flourishing and contactless
      conductivity measurements are increasingly being employed as part of novel or
      more sophisticated experimental systems. Work on the lab-on-chip devices
      integrating contactless conductivity detection is continuing. A range of reports
      on the use of the simple yet powerful detection technique of contactless
      conductivity measurements in chromatographic separation as well as for analytical
      methods not including a separation step have also appeared.

PMID- 23161280
TI  - Reversal of thienopyridine-induced platelet dysfunction following desmopressin
      administration.
AB  - Adenosine diphosphate (ADP)-receptor antagonists are widely used for thrombus
      prevention, although reversing their platelet dysfunction is difficult. This
      study evaluated the ability of desmopressin to reverse clopidogrel-induced
      platelet dysfunction. Sprague-Dawley rats received either clopidogrel (30 mg/kg)
      or placebo, followed 4 h later by saline or desmopressin (0.15, 0.3, or 0.6
      MUg/kg). Bleeding times and platelet aggregation studies were subsequently
      performed. A bleeding time >25 min was considered "prolonged." The median
      bleeding time for clopidogrel-exposed rats was 21 min, vs. 6 min for controls (p
      < 0.01). Progressively higher doses of 1-deamino-8-D-arginine vasopressin (DDAVP)
      were associated with a reduced number of rats with prolonged bleeding time (p =
      0.001). Higher doses of DDAVP were also associated with a reduction in the median
      (IQR) bleeding time; 29 (13.5-30) min in rats receiving clopidogrel without DDAVP
      vs. 19 (12-28) min in rats receiving clopidogrel and 0.6 MUg/kg DDAVP. The step
      wise dosing of DDAVP resulted in a 54 % reduction in meeting the endpoint of
      prolonged bleeding time (OR 0.46; p = 0.025; 95 % CI 0.23-0.91). Platelet
      aggregation was observed in all control rats, but only some of those clopidogrel
      treated rats who received 0.6 MUg/kg DDAVP. In this model of an ADP-receptor
      antagonist, DDAVP results in partial reversal of clopidogrel-induced platelet
      dysfunction.

PMID- 23161281
TI  - Systematic review and meta-analysis of randomized clinical trials comparing
      single-incision versus conventional laparoscopic cholecystectomy.
AB  - BACKGROUND: Single-incision laparoscopic cholecystectomy (SILC) may offer
      advantages over conventional laparoscopic cholecystectomy (LC). METHODS: MEDLINE,
      Embase, PubMed, CINAHL, Cochrane Central Register of Controlled Trials and the
      Cochrane Library were searched for randomized clinical trials on SILC versus LC
      until May 2012. Odds ratio (OR) and weight mean difference (WMD) were calculated
      with 95 per cent confidence intervals (c.i.) based on intention-to-treat
      analysis. RESULTS: Thirteen randomized clinical trials included a total of 923
      procedures. SILC had a higher procedure failure rate than LC (OR 8.16, 95 per
      cent c.i. 3.42 to 19.45; P < 0.001), required a longer operating time (WMD 16.55,
      95 per cent c.i. 9.95 to 23.15 min; P < 0.001) and was associated with greater
      intraoperative blood loss (WMD 1.58, 95% of c.i. 0.44 to 2.71 ml; P = 0.007).
      There were no differences between the two approaches in rate of conversion to
      open surgery, length of hospital stay, postoperative pain, adverse events, wound
      infections or port-site hernias. Better cosmetic outcomes were demonstrated in
      favour of SILC as measured by Body Image Scale questionnaire (WMD -0.97, 95% of
      c.i. -1.51 to -0.43; P < 0.001) and Cosmesis score (WMD -2.46, 95% of c.i. -2.95
      to -1.97; P < 0.001), but this was based on comparison with procedures in which
      multiple and often large ports (10 mm) were used. CONCLUSION: SILC has a higher
      procedure failure rate with more blood loss and takes longer than LC. No trial
      was adequately powered to assess safety.

PMID- 23161282
TI  - Enhanced separation of Compound Xueshuantong capsule using functionalized carbon
      nanotubes with cationic surfactant solutions in MEEKC.
AB  - A novel additive of multi-walled carbon nanotubes (MWNTs) dispersed with cationic
      surfactants or mixed cationic/anionic surfactants was used for MEEKC separation
      of eight phenolic compounds, four glycosides, and one phenanthraquinone. In this
      context, several parameters affecting MEEKC separation were studied, including
      the dispersion agents of MWNTs, MWNTs content, oil type, SDS concentration, and
      the type and concentration of cosurfactant. Compared with conventional MEEKC, the
      addition of all types of MWNTs dispersions using single or mixed cationic
      surfactant solutions in running buffers was especially useful for improving the
      separation of solutes tested, as they influenced the partitioning between the oil
      droplets and aqueous phase due to the exceptional electrical properties and large
      surface areas of MWNTs. Use of cationic surfactant-coated MWNTs (6.4 MUg/mL) as
      the additive in a microemulsion buffer (0.5% octanol, 2.8% SDS, 5.8% isopropanol,
      and 5 mM borate buffer) yielded complete resolution of 13 analytes. The proposed
      method has been successfully applied for the detection and quantification of the
      studied compounds in a complex matrix sample (Compound Xueshuantong capsule).

PMID- 23161283
TI  - SNPs in toll-like receptor (TLR) genes as new genetic alterations associated with
      congenital toxoplasmosis?
AB  - Nearly 40 % of pregnant women are infected with Toxoplasma gondii. Primary
      infections in pregnant women result, in approximately 30-50 % of patients, in
      transmission of T. gondii through the placenta to the fetus and then in
      congenital infections with severe, sometimes fatal course. Studies still do not
      provide sufficient data on the genetic bases of the immunity in fetuses,
      newborns, and infants with congenital toxoplasmosis. Previous research showed the
      contribution of toll-like receptors (TLRs) to non-specific immunity against T.
      gondii invasion, observed in T. gondii-infected animals, especially mice. So far,
      the activity of TLRs in defense against T. gondii infections was observed
      particularly for TLR2, TLR4, and TLR9 molecules. Differential TLR activity
      associates with both cell types, including a variety of placental cells and stage
      of pregnancy. Several single-nucleotide polymorphisms (SNPs) residing in three
      genes encoding these receptors were reported as significant genetic modifications
      of TLRs associated with different pregnancy disorders. Despite those data,
      genetic alterations of TLRs which have contributed to innate immune response
      against T. gondii infections are still not precisely described. In this article,
      we present reasons for the research of the plausible role of SNPs residing in
      TLR2, TLR4, and TLR9 genes in congenital toxoplasmosis development.

PMID- 23161284
TI  - CXCL14 enhances proliferation and migration of NCI-H460 human lung cancer cells
      overexpressing the glycoproteins containing heparan sulfate or sialic acid.
AB  - CXCL14 is a chemokine family member that is involved in various cellular
      responses in addition to immune cell activation. Although constitutive CXCL14
      expression in normal epithelial cells may help protect against infection by
      activating immune systems, its expression in cancer cells has raised controversy
      regarding its possible role in tumorigenesis. However, the underlying mechanisms
      for this disparity remain unknown. Investigation of cellular CXCL14 binding
      properties might increase our understanding of the peptide's roles in
      tumorigenesis. In the present study, we found that CXCL14 binds to various cell
      types. Interestingly, binding to NCI-H460 cells was prevented by heparan sulfate
      and N-acetyl neuraminic acid. Next, we examined effect of CXCL14 binding in NCI
      H460 and NCI-H23. CXCL14 enhanced proliferation and migration in NCI-H460 but had
      no effect on NCI-H23. A reporter gene assay with various transcription factor
      response elements revealed that only nuclear factor-kappaB (NF-kappaB) signaling
      was activated by CXCL14 in NCI-H460 cells, which was blocked by BAPTA-AM, TPCA-1,
      and brefeldin A. Exogenous expression of some glycoproteins such as syndecan-4,
      podoplanin, and CD43 in these cells enhanced CXCL14 binding and NF-kappaB
      activity. Collectively, these results demonstrate that CXCL14 binding to
      glycoproteins harboring heparan sulfate proteoglycans and sialic acids leads
      proliferation and migration of some cancer cells.

PMID- 23161286
TI  - Differential haplotype amplification leads to misgenotyping of heterozygote as
      homozygote when using single nucleotide mismatch primer.
AB  - Mismatches at the 3'end of /or within a primer are reported to affect the
      efficiency of PCR and cause allele drop. Here, we report preferential
      amplification of one haplotype and misgenotyping, when double heterozygotes at
      NAT1 (rs1057126 and rs15561) were genotyped by sequencing and PCR-RFLP methods
      using mismatch reverse primers located next to the target SNP. Detailed study
      revealed highest (100%) and lowest (0%) misgenotyping when the mismatch was at
      the 3rd and 15th nucleotide positions from 3' end of the primer, respectively.
      But, the same primers, without any mismatch genotyped heterozygotes correctly.
      Homozygotes can always be detected correctly irrespective of mismatch position in
      the primer. Similar results were observed for two SNPs (rs12947788 and rs
      12951053) at TP53. Using mismatch NAT1 reverse primers, located three nucleotides
      away from the target SNP, both TaqMan and sequencing methods showed preferential
      synthesis of one haplotype strand and misgenotyping in heterozygotes,
      respectively. So, mismatch primer, located next to target SNP, should be avoided
      to genotype heterozygotes, since, PCR and sequencing based genotyping methods may
      lead the investigators to report faulty allelic and genotypic frequencies. This
      study mimics a situation when an unknown variation is present in the primer
      binding sites of both chromosomes.

PMID- 23161287
TI  - Systemic treatment of neuroendocrine tumors with hepatic metastases.
AB  - Neuroendocrine tumors, 1-2% of all malignancies, are relatively slow-growing
      neoplasms. The majority of neuroendocrine tumors belong to the World Health
      Organization Group 2 with well-differentiated endocrine carcinomas, but some
      tumors can be aggressive. The most common are gastroenteropancreatic
      neuroendocrine tumors, followed by bronchopulmonary neuroendocrine tumors; less
      frequent locations are the ovaries, testis and hepatobiliary locations. They can
      be either non-functioning tumors with symptoms related to mass effects and
      malignant tumor disease or functioning tumors with specific
      hormones/neuropeptides autonomously secreted to induce specific clinical
      syndromes. Localized neuroendocrine tumors are less frequent than metastatic
      ones; in fact, up to 75% of patients with small bowel neuroendocrine tumors and
      30-85% of pancreatic neuroendocrine tumors present with liver metastases either
      at the time of diagnosis or during the course of the disease. The predominant
      metastatic site is the liver, which is the best prognostic marker of survival
      regardless of the primary site. If surgical resection or interventional therapies
      of the hepatic tumor burden are not feasible, or if the metastases are not
      confined to the liver, systemic treatment remains the only option. None of the
      systemic therapies is liver-specific, but rather acts on all metastatic sites.
      The lack of prospective studies comparing different treatment modalities in
      homogeneous cohorts of patients makes the best treatment strategy poorly defined.
      Standard systemic therapy options are somatostatin analogues (octreotide and
      lanreotide), interferon-alpha and chemotherapy. Somatostatin analogues not only
      control symptoms related to functioning tumors but tumor growth as well. Because
      of the studies challenging its efficacy, as well as the potential for side
      effects, the more widespread acceptance of interferon-alpha in the treatment of
      metastatic neuroendocrine tumors has been limited. Well-differentiated
      neuroendocrine tumors do not show high sensitivity to chemotherapy because of
      their low mitotic rates, high levels of antiapoptotic protein bcl-2 and increased
      expression of the multi-drug resistant gene. Traditional chemotherapeutic agents
      are streptozotocin in combination with 5-fluorouracil or doxorubicin, or to some
      extent dacarbazine. Temozolomide, capecitabine and oxaliplatin, as monoagents or
      in combination therapy, show efficacy in phase II trials. Patients with poorly
      differentiated neuroendocrine tumor, regardless of the primary tumor
      localization, are candidates for cisplatin and etoposide chemotherapy regimen.
      Peptide receptor radionuclide therapy is reported to be an effective treatment
      option for patients with good performance status and high somatostatin-receptor
      scintigraphy uptake as well as without major liver involvement. Basic fibroblast
      growth factor, vascular endothelial growth factor, platelet-derived growth
      factor, transforming growth factor alpha and beta, insulin-like growth factor
      type 1, epidermal growth factor, stem cell factor (c-kit), and corresponding
      receptors have been shown to be expressed in Neuroendocrine tumors. Current phase
      II-III clinical trials with molecular-targeted therapies revealed promising
      agents such as everolimus (RAD001), an oral mTOR inhibitor, and sunitinib malate
      (SU-11248), an oral multitargeted tyrosine kinase inhibitor against vascular
      endothelial growth factor receptors, platelet-derived growth factor receptors, c
      kit receptors, glial cell linederived neurotrophic factor, and FMS-like tyrosine
      kinase-3 (Flt 3), which were approved for the treatment of advanced pancreatic
      neuroendocrine tumors. Ongoing clinical trials with bevacizumab, a humanized
      monoclonal antibody against vascular endothelial growth factor, will further
      define the role of angiogenesis inhibitors in advanced intestinal neuroendocrine
      tumors. Various further novel strategies of targeted therapy and microRNA
      regulated pathways in neuroendocrine tumors are under development.

PMID- 23161288
TI  - In vitro effects of famotidine and ranitidine on lower esophageal sphincter tone
      in rats.
AB  - BACKGROUND/AIMS: The aim of this study was to investigate the effects of the H2
      receptor antagonists famotidine and ranitidine on lower esophageal sphincter
      pressure in the rat isolated lower esophageal sphincter preparation contracted
      with carbachol. MATERIALS AND METHODS: Lower esophageal sphincter tissues of
      eight rats for each group were placed in a standard organ bath. After contraction
      with carbachol, freshly prepared famotidine and ranitidine were added directly to
      the tissue bath in cumulatively increasing concentrations. Activities were
      recorded on an online computer using the software BSL PRO v 3.7, which also
      analyzed the data. RESULTS: Ranitidine caused a small statistically insignificant
      relaxation in the contracted lower esophageal sphincter at the two applied
      concentrations. Although 1.5 x 10-5 M famotidine did not cause a significant
      relaxation in lower esophageal sphincter tone, this value for 4.5 x 10-5 M
      famotidine was 9.33%, and the relaxation was significant when compared with
      controls (p<0.05). CONCLUSIONS: Neither famotidine nor ranitidine caused any
      direct significant change in lower esophageal sphincter tone in the therapeutic
      dose range applied to the organ bath. However, the higher dose of famotidine
      caused a significant relaxation in the lower esophageal sphincter tone. Further
      in vivo human studies may affect the usage of these drugs during gastroesophageal
      reflux disease treatment.

PMID- 23161285
TI  - New paradigms in post-hepatectomy liver failure.
AB  - INTRODUCTION: Liver failure after hepatectomy remains the most feared
      postoperative complication. Many risk factors are already known, related to
      patient's comorbidities, underlying liver disease, received treatments and type
      of resection. Preoperative assessment of functional liver reserve must be a
      priority for the surgeon. METHODS: Physiopathology of post-hepatectomy liver
      failure is not comparable to fulminant liver failure. Liver regeneration is an
      early phenomenon whose cellular mechanisms are beginning to be elucidated and
      allowing most of the time to quickly recover a functional organ. In some cases,
      microscopic and macroscopic disorganization appears. The hepatocyte
      hyperproliferation and the asynchronism between hepatocytes and non-hepatocyte
      cells mitosis probably play a major role in this pathogenesis. RESULTS: Many peri
      or intra-operative techniques try to prevent the occurrence of this potentially
      lethal complication, but a better understanding of involved mechanisms might help
      to completely avoid it, or even to extend the possibilities of resection.
      CONCLUSION: Future prevention and management may include pharmacological slowing
      of proliferation, drug or physical modulation of portal flow to reduce shear
      stress, stem cells or immortalized hepatocytes injection, and liver bioreactors.
      Everything must be done to avoid the need for transplantation, which remains
      today the most efficient treatment of liver failure.

PMID- 23161289
TI  - Evaluation of serum ghrelin levels in patients with hyperplastic gastric polyps.
AB  - BACKGROUND/AIMS: Ghrelin is a 28 amino acid peptide and the main source of serum
      ghrelin is the stomach. The aim of this study was to evaluate serum ghrelin
      levels in patients with hyperplastic gastric polyp. MATERIALS AND METHODS: Eighty
      patients (50 female, 30 male) were included in this study: 28 with hyperplastic
      gastric polyp, 20 with benign gastric ulcer and 32 with chronic active gastritis.
      Serum ghrelin levels were measured by radioimmunoassay method. RESULTS: Serum
      ghrelin level was significantly lower in patients with hyperplastic gastric polyp
      (1139.86 +/- 279.23 pg/ml) than in those with benign gastric ulcer (1362.45 +/-
      335.35 pg/ml) and chronic active gastritis (1362.91 +/- 269.67 pg/ml) (p=0.016
      and p=0.003, respectively). The benign gastric ulcer and chronic active gastritis
      groups had similar serum values (p=0.996). Serum ghrelin level was not affected
      by Helicobacter pylori, with levels of 1298.70 +/- 309.01 pg/ml and 1252.12 +/-
      303.04 pg/ml in 56 positive and 24 negative patients, respectively (p=0.536). In
      the patients with hyperplastic gastric polyp, Helicobacter pylori infection was
      found to have no effect on serum ghrelin level (p=0.855). CONCLUSIONS: Serum
      ghrelin levels of patients with hyperplastic gastric polyp were lower than in
      patients with benign gastric ulcer and chronic active gastritis. In patients with
      various benign stomach lesions, the presence of Helicobacter pylori does not seem
      to affect serum ghrelin levels.

PMID- 23161290
TI  - Effects of statins in an indomethacin-induced gastric injury model in rats.
AB  - BACKGROUND/AIMS: Statins have additional pleiotropic effects beyond their lipid
      lowering effects. In this study, the effects of statins were evaluated in an
      indomethacin-induced gastric injury model in rats. MATERIALS AND METHODS: Animals
      were divided into eight groups. Distilled water (control group), omeprazole (30
      mg/kg), atorvastatin (20 and 40 mg/kg), simvastatin (20 and 40 mg/kg), and
      rosuvastatin (20 and 40 mg/kg) were given orally (gavage). Thirty minutes later,
      indomethacin (25 mg/kg) was administered orally to all groups. Six hours later,
      the animals were sacrificed by decapitation. The mean ulcer indexes for each
      group were calculated, and the stomachs were evaluated histopathologically.
      RESULTS: The ulcer indexes were as follows: control 1.72 +/- 0.16, omeprazole 0
      +/- 0.00, and atorvastatin, simvastatin and rosuvastatin (at 20 and 40 mg/kg
      doses, respectively) 4.28 +/- 0.39, 4.99 +/- 0.96, 1.72 +/- 0.73, 1.90 +/- 0.48,
      1.85 +/- 0.26, and 1.67 +/- 0.18. Atorvastatin significantly increased the
      indomethacin-induced ulcer index at both doses and the erosion score at 40 mg/kg
      dose. Although the 20 mg/kg dose of simvastatin inhibited mononuclear leukocyte
      infiltration, the 40 mg/kg dose induced hyperemia. Rosuvastatin did not decrease
      mononuclear leukocyte or neutrophil infiltrations at 20 mg/kg dose, and only
      neutrophil infiltration at the 40 mg/kg dose. CONCLUSIONS: In patients with
      gastric discomfort, statins must be used carefully. If statin therapy is needed,
      we recommend to avoid using atorvastatin and to use the other statins only in the
      minimum effective dose.

PMID- 23161291
TI  - An observational European study on clinical outcomes associated with current
      management strategies for non-variceal upper gastrointestinal bleeding (ENERGIB
      Turkey).
AB  - BACKGROUND/AIMS: This observational, retrospective cohort study assessed outcomes
      of the current management strategies for nonvariceal upper gastrointestinal
      bleeding in several European countries (Belgium, Greece, Italy, Norway, Portugal,
      Spain, and Turkey) (NCT00797641; ENERGIB). MATERIALS AND METHODS: Turkey
      contributed 23 sites to this study. Adult patients (>=18 years old) consecutively
      admitted to hospital and who underwent endoscopy for overt non-variceal upper
      gastrointestinal bleeding (hematemesis, melena or hematochezia, with other
      clinical/laboratory evidence of acute upper GI blood loss) were included in the
      study. Data were collected from patient medical records regarding bleeding
      continuation, re-bleeding, pharmacological treatment, surgery, and mortality
      during a 30-day follow-up period. RESULTS: A total of 423 patients (67.4% men;
      mean age: 57.8 +/- 18.9 years) were enrolled in the Turkish study centers, of
      whom 96.2% were admitted to hospital with acute non-variceal upper
      gastrointestinal bleeding. At admission, the most common symptom was melena
      (76.1%); 28.6% of patients were taking aspirin, 19.9% were on non-steroidal anti
      inflammatory drugs, and 7.3% were on proton pump inhibitors. The most common
      diagnoses were duodenal (45.2%) and gastric (27.7%) ulcers and gastritis/gastric
      erosions (26.2%). Patients were most often managed in general medical wards
      (45.4%). A gastrointestinal team was in charge of treatment in 64.8% of cases.
      Therapeutic procedures were performed in 32.4% of patients during endoscopy.
      After the endoscopy, most patients (94.6%) received proton pump inhibitors. Mean
      (SD) hospital stay was 5.36 +/- 4.91 days. The cumulative proportions of
      continued bleeding/re-bleeding, complications and mortality within 30 days of the
      non-variceal upper gastrointestinal bleeding episode were 9.0%, 5.7% and 2.8%,
      respectively. In the Turkish sub-group of patients, the significant risk factors
      for bleeding continuation or re-bleeding were age >65 years, presentation with
      hematemesis or shock/syncope, and the diagnosis of duodenal ulcer. The risk of
      clinical complications after non-variceal upper gastrointestinal bleeding was
      higher in female patients older than 65 years, in patients with comorbidities,
      and in patients presenting with shock/syncope, and also according to time to
      endoscopy. The use of aspirin, non-steroidal anti-inflammatory drugs or warfarin
      at baseline was negatively associated with the development of bleeding or
      clinical complications. The risk of death within 30 days after non-variceal upper
      gastrointestinal bleeding was significantly higher in patients older than 65
      years and in those receiving transfusions other than intravenous fluid or red
      blood cells within 12 hours of presentation. CONCLUSIONS: According to the survey
      results, non-variceal upper gastrointestinal bleeding in Turkey varies from that
      in other European countries in a number of aspects. These differences could be
      associated with a younger population and Helicobacter pylori incidence. Despite
      the diminishing need for surgical intervention and mortality rates for non
      variceal upper gastrointestinal bleeding, as is the case in other European
      countries, non-variceal upper gastrointestinal bleeding remains a serious
      problem.

PMID- 23161293
TI  - Double-balloon endoscopy in patients with Peutz-Jeghers syndrome.
AB  - BACKGROUND/AIMS: Peutz-Jeghers syndrome is a rare hereditary syndrome
      characterized by mucocutaneous pigmentation and hamartomatous polyps of the
      gastrointestinal tract, especially in the small intestine. Double-balloon
      endoscopy is a new endoscopic technique that enables both endoscopic
      visualization of the entire small bowel and therapeutic interventions in a single
      procedure. In this study, we evaluate the efficacy and safety of double-balloon
      endoscopy for both treatment and surveillance of patients with Peutz-Jeghers
      syndrome. MATERIALS AND METHODS: We retrospectively evaluated 7 consecutive
      patients who were referred to Dokuz Eylul University, Gastroenterology
      Department, with the diagnosis of Peutz-Jeghers syndrome between 2007 and 2010.
      RESULTS: Patients with Peutz-Jeghers syndrome (M/F: 5/2) underwent a total 31
      double-balloon endoscopy procedures: 21 by the oral route, 9 by the anal route,
      and 1 intraoperatively. All of the patients had a history of laparotomy and small
      bowel resection due to complications such as invagination and ileus. In 7
      patients, we found a total of 110 polyps >=10 mm in diameter (10-100 mm) and
      polypectomies were performed in all of them. The only complication was a bleeding
      after polypectomy, which was controlled by sclerotherapy. In 1 patient, because
      of the intraabdominal adhesions due to past laparotomies, polypectomy was done by
      intraoperative endoscopy. In 2 of our patients, we made surveillance
      colonoscopies, found new polyps in the small intestine, and performed
      polypectomies. CONCLUSIONS: Double-balloon endoscopy is an effective and safe
      endoscopic technique, and represents a milestone for both treatment and
      surveillance of patients with Peutz-Jeghers syndrome. Polypectomies made in the
      small intestine might decrease the complication rate due to these polyps and the
      need for surgery.

PMID- 23161292
TI  - Celiac disease prevalence in patients with iron deficiency anemia.
AB  - BACKGROUND/AIMS: Iron deficiency anemia may be the first presenting finding of
      celiac disease, which is a common autoimmune disorder triggered by the intake of
      certain proteins. The aim of this study was to determine the prevalence of celiac
      disease in patients with iron deficiency anemia of obscure origin. MATERIALS AND
      METHODS: Eighty-four patients with the diagnosis of iron deficiency anemia of
      obscure origin were included in the study. Histologic findings for celiac disease
      were investigated in biopsy specimens taken from the second part of the duodenum
      of all subjects. Patients were also screened using anti-endomysial and anti
      gliadin antibodies. The diagnosis of celiac disease was confirmed by both
      serological positivity and histopathological findings. RESULTS: In 6 of 84
      patients (7.14%), both serologic and histopathologic findings were correlated
      with celiac disease. After six months under a gluten-free diet, their mean
      hemoglobin levels increased from 10.3 +/- 0.64 to 12.97 +/- 1.48 g/dl (p=0.002).
      One patient with positive serology for celiac disease but normal duodenal mucosal
      biopsies also improved clinically after a gluten-free diet at the end of the
      follow-up and was considered as celiac disease. Six of these 7 celiac disease
      patients (85.7%) were premenopausal women, with a mean age of 37.5 +/- 8.45
      years. CONCLUSIONS: Clinicians should consider celiac disease as a possible cause
      of anemia in all patients with iron deficiency anemia of obscure origin, even in
      menstruating women. Serologic screening tests should be performed in
      premenopausal women with iron deficiency anemia, especially when anemia is
      refractory to oral iron treatment.

PMID- 23161294
TI  - Fecal calprotectin concentration is increased in children with celiac disease:
      relation with histopathological findings.
AB  - BACKGROUND/AIMS: The aim of this study was to compare the fecal calprotectin
      concentration in children with newly diagnosed celiac disease, children with
      celiac disease strictly adhering to a gluten-free diet and healthy controls. We
      also tried to correlate the fecal calprotectin concentration with the clinical
      presentation, degree of neutrophilic infiltration and the severity of
      histopathological injury (Marsh grade) in the small bowel mucosa. MATERIAL AND
      METHODS: The study included three groups: children with untreated celiac disease,
      children with treated celiac disease, and healthy controls. Moreover, we obtained
      a second fecal sample from nine newly diagnosed children when their endomysial
      antibody became negative after gluten-free diet. RESULTS: Fecal calprotectin
      concentrations were significantly higher in newly diagnosed celiac patients
      (n=31) compared to patients on gluten-free diet (n=33) and healthy controls
      (n=34) (117.2 MUg/g (3.2-306) vs. 3.7 MUg/g (0.5-58.2) and 9.6 MUg/g (1-70),
      respectively, p<0.001). Patients presenting with gastrointestinal symptoms had
      higher fecal calprotectin concentration compared to the patients presenting with
      nongastrointestinal symptoms [142.8 (12.2-306) vs. 79.7 (3.2-243.2) respectively,
      p=0.04]. Nine newly diagnosed patients gave a second fecal sample after starting
      gluten-free diet when endomysial antibody became negative. Their fecal
      calprotectin concentration had decreased from 113.7 MUg/g (8.7-295.2) to 4.2
      MUg/g (0.5-20.7) (p<0.01). CONCLUSIONS: Increased fecal calprotectin
      concentration can be used as a non-invasive marker that might aid in the
      diagnosis of celiac disease, especially in patients with gastrointestinal
      presentation. Fecal calprotectin concentration returns to normal on a strict
      gluten-free diet. Fecal calprotectin may be used as a marker of diet adherence
      and improvement in gastrointestinal inflammation in children with celiac disease.
      Additionally, it may be used for the differentiation of celiac disease from
      functional disorders of the gastrointestinal system.

PMID- 23161295
TI  - The value of fecal calprotectin as a marker of intestinal inflammation in
      patients with ulcerative colitis.
AB  - BACKGROUND/AIMS: To assess intestinal inflammation, simple, inexpensive and
      objective tools are desirable in inflammatory bowel disease. This study aimed to
      evaluate fecal calprotectin as a marker of active disease in ulcerative colitis.
      MATERIALS AND METHODS: Sixty patients with a diagnosis of ulcerative colitis and
      20 controls were recruited into the study. The disease activity of ulcerative
      colitis was determined by modified Truelove-Witts criteria and Rachmilewitz
      endoscopic index. The enzyme-linked immunosorbent assay was used to measure the
      concentrations of fecal calprotectin. C-reactive protein, erythrocyte
      sedimentation rate and hemogram were also measured, and inflammatory markers were
      compared with fecal calprotectin in determining disease activity. RESULTS: Fecal
      calprotectin concentration in the patients with active ulcerative colitis (n=30)
      was significantly higher than that in the inactive ulcerative colitis group
      (n=30) and in the controls (n=20) (95% confidence interval: 232.5 (0.75-625) vs
      11.7 (0.2-625), 7.5 (0.5-512) mg/L, p<0.001). There was no significant difference
      between the patients with inactive ulcerative colitis and controls (p>0.05). The
      calprotectin concentration was greater in the patients with a more severe
      clinical index, higher endoscopic activity (>4), elevated C-reactive protein,
      leukocytosis, and extensive colitis (p<0.05). The areas under the curve of the
      receiver operating characteristics were 0.817, 0.809, 0.532, and 0.507 for C
      reactive protein, fecal calprotectin, leukocyte count, and erythrocyte
      sedimentation rate, respectively. There was a significant correlation between the
      fecal calprotectin concentration and the endoscopic activity in ulcerative
      colitis (r = 0.548, p<0.001). CONCLUSIONS: Fecal calprotectin is a useful marker
      in the diagnosis of active disease and evaluation of clinical and endoscopic
      activity in ulcerative colitis.

PMID- 23161296
TI  - Impact of an information video before colonoscopy on patient satisfaction and
      anxiety.
AB  - BACKGROUND/AIMS: Anxiety is a common problem in patients undergoing invasive
      medical procedures. Colonoscopy is a demanding procedure and requires a patient's
      good cooperation for successful results. We aimed to examine the effects of
      adding an information video to our usual preprocedural information. MATERIALS AND
      METHODS: A total of 227 patients were assessed in this study (120 male, 107
      female). The patients were divided into two groups as video (n=124) or verbal
      (n=103). When the patients in the polyclinic with indications for colonoscopy
      were selected, a text about the procedure and related complications was given to
      them. A colonoscopy appointment was scheduled for the patients 3-4 weeks
      following the procedure. On the appointment day, the patients selected randomly
      in groups of 10 as either verbal or video sections were taken into the
      communication room 1-5 hours before the procedure. The patients' anxiety was
      measured afterwards using the Spielberger State-Trait Anxiety Inventory
      questionnaire. In addition, patients answered individual questions. After the
      colonoscopy, the patients were asked if they would undergo colonoscopy again for
      health reasons and whether the procedure was similar to, better, or worse than
      they had expected (following the information sessions). RESULTS: It was noted in
      univariate and multiple logistic regression analyses that low State-Trait Anxiety
      Inventory-State levels (p<=0.001 and p=0.016, respectively) and communication by
      video (p<0.001, p=0.007, respectively) had a significant impact on communication
      success. CONCLUSIONS: An information video shown to patients preparing for
      colonoscopy had an impact on the success of the procedure and on anxiety.

PMID- 23161297
TI  - The efficacy of endoscopic ultrasonography in local staging of rectal tumors.
AB  - BACKGROUND/AIMS: The purpose of this study was to research the efficacy and
      reliability of endoscopic rectal ultrasonography in local staging (T and N
      stages) of rectal tumors. MATERIALS AND METHODS: This retrospective study was
      carried out by the Department of Gastroenterology, Izmir Ataturk Training and
      Research Hospital, which is tertiary level. Thirty-one patients with
      adenocarcinoma were included in the study. The patients found operable according
      to computed tomography underwent preoperative local staging by endoscopic
      ultrasonography. Radial endoscopic ultrasonography and T and N stages were
      evaluated. RESULTS: It was observed that endoscopic rectal ultrasonography had
      80.6% accuracy, 93.4% sensitivity, and 96.5% specificity in T stage; 70%
      accuracy, 70% sensitivity, and 86% specificity in the detection of presence of
      lymph node; and 76% accuracy, 100% sensitivity, and 22% specificity in the
      detection of the nature of lymph node. CONCLUSIONS: In this study, it was
      observed that endoscopic rectal ultrasonography is an efficient and reliable
      method in the detection of local lymph node and the depth of invasion of rectal
      tumors (T staging), although it is not reliable enough to determine the
      characteristics of lymph nodes.

PMID- 23161298
TI  - Evaluation of the risk factors of pilonidal sinus: a single center experience.
AB  - BACKGROUND/AIMS: We aimed to evaluate which factors, if prevented, could
      facilitate a decrease in the rate of pilonidal sinus. MATERIALS AND METHODS: From
      November 2008 to 2010, all patients referred to the surgery clinic were examined
      by the general surgery attending physician. Patients with a diagnosis of
      pilonidal sinus were considered as the trial group. The control group included
      healthy persons who accompanied the patients to the clinic. Both groups completed
      a questionnaire form, which included age, sex, occupation, weight, height, number
      of baths taken per week, mean duration of sitting and driving, and family history
      of pilonidal sinus. The Statistical Package for the Social Sciences software was
      used to analyze the data. RESULTS: Positive family history was seen in 71.7% of
      patients compared to 23.2% of the control group. 70.7% of patients had body mass
      index >25, whereas only 12.9% of the control group were overweight. P value was
      significant for family history and body mass index >25. Long duration of sitting
      was seen in 66.7% of patients vs. 22.8% of the control group (p: 0.002). Long
      duration of driving was reported in 70.7% of the patient group compared to 24.8%
      of the control group (p: 0.001). Irregular hygiene of the sacrococcygeal region
      was noted in 74.7% of the patient group, while 40.6% of the control group took
      baths less than three times per week (p value was significant). Pilonidal sinus
      was seen in 39.4% of drivers in the patient group and in 23.8% of the control
      group (p: 0.012). P value was not significant between students in the patient and
      control groups (30.3% vs. 23.8%, respectively). CONCLUSIONS: Weight loss and
      regular hygiene, especially in patients with long durations of sitting and/or
      driving, are the suggested preventative measures to decrease the risk of disease.

PMID- 23161299
TI  - Simple non-invasive markers as a predictor of fibrosis and viral response in
      chronic hepatitis C patients.
AB  - BACKGROUND/AIMS: Chronic hepatitis C has a high prevalence and leads to
      development of cirrhosis and hepatocellular carcinoma. Liver fibrosis staging is
      one of the main factors that influence the decision to indicate therapy for
      chronic hepatitis C carriers. Several simple laboratory tests, scores and indices
      have been proposed for the non-invasive prediction of hepatic fibrosis in
      patients with chronic hepatitis C. The purpose of this study was to evaluate non
      invasive liver fibrosis tests as a predictive factor of fibrosis and non
      sustained viral response (relapse/non-responder) in chronic hepatitis C naive
      patients. MATERIALS AND METHODS: We performed a retrospective case-control study
      with utilization of non-invasive liver fibrosis test, platelet count, aspartate
      aminotransferase/alanine aminotransferase ratio, age-platelet index and aspartate
      aminotransferase to platelet ratio index, as a predictor of non-sustained viral
      response in chronic hepatitis C naive patients between July 2008 and August 2010
      in Izmir Ataturk Training and Research Hospital. RESULTS: We observed non
      invasive liver fibrosis test to be highly effective in predicting non-sustained
      viral response patients, especially with age-platelet index (Accuracy=73%,
      OR=6.93, 95% CI, 2.41-19.8). A strong relationship was shown with multivariate
      analysis between non-sustained viral response and some non-invasive liver
      fibrosis tests such as viral load (OR=4.51, 95% CI, 1.16 -17.6, p=0.03) and age
      platelet index (OR=11.8, 95% CI, 2.25-62.15, p=0.004). CONCLUSIONS: If non
      invasive tests could be standardized according to age, gender, race, and body
      mass index and individualized according to the fibrosis, then a nearly full
      correlation of non-invasive liver fibrosis test with histologic results could be
      obtained, stage of fibrosis could be predicted initially, sustained viral
      response/non-sustained viral response could be estimated, and the need for a
      repeat biopsy could be eliminated.

PMID- 23161300
TI  - Experience in primary hepatic neuroendocrine tumor.
AB  - BACKGROUND/AIMS: We aimed to analyze the clinical characteristics, pathologic
      features, treatment approaches, and prognostic factors of primary hepatic
      neuroendocrine tumor. MATERIALS AND METHODS: We retrospectively analyzed the
      clinical characteristics, pathologic features, treatment approaches, and
      prognostic factors of 9 patients with primary hepatic neuroendocrine tumor
      treated in our hospital from January 2003 to January 2010. RESULTS: The clinical
      manifestations were nonspecific and variable. The most common clinical
      manifestation was distention or right upper quadrant pain. Radiological findings
      are not specific and cannot distinguish primary hepatic neuroendocrine tumor from
      hepatocellular carcinoma. Diagnosis of primary hepatic neuroendocrine tumor was
      confirmed immunohistochemically and by the absence of extrahepatic primary sites.
      No extrahepatic primary lesions were found by ultrasonography, computed
      tomography, magnetic resonance imaging or positron emission tomography scan
      either preoperatively or during the follow-up period in our research.
      Immunohistologically, synaptophysin, chromogranin A and CD56 should be used as
      markers to precisely diagnose primary hepatic neuroendocrine tumor. The outcome
      of primary hepatic neuroendocrine tumor is mostly related to its resectability.
      Total resection of the neoplasm is most commonly proposed. A multimodality of
      treatments, including chemotherapy, transarterial chemoembolization and
      radiofrequency ablation, should be used preor postoperatively to improve the
      survival. CONCLUSIONS: Primary hepatic neuroendocrine tumor is a rare entity, and
      its diagnosis is difficult. Preoperative fine needle biopsy is strongly
      recommended, and primary surgery integrated with chemotherapy, transarterial
      chemoembolization or radiotherapy is considered to be an effective modality for
      primary hepatic neuroendocrine tumor.

PMID- 23161301
TI  - Safety of peginterferon alfa-2a (40KD) treatment in patients with chronic
      hepatitis B infection: an observational, multicenter, open label, non
      interventional study in Turkish patients.
AB  - BACKGROUND/AIMS: Pegylated alfa interferon is the only immunomodulatory drug
      licensed for hepatitis B. We evaluated the safety and tolerability of
      peginterferon alfa-2a (40KD) in patients with chronic hepatitis B. MATERIALS AND
      METHODS: A total of 113 chronic hepatitis B patients under peginterferon alfa-2a
      (40KD; 180 MUg/week) treatment were included in this multicenter, open label, non
      interventional study, and 66 patients completed the follow-up period. Vital
      signs, physical examination and laboratory findings, concomitant medications, and
      adverse events were recorded. A Quality of Life questionnaire (Short Form-36) was
      performed twice, at the beginning and at the end of the study. RESULTS: There was
      no significant difference between initial and last visits in terms of physical
      examination findings and Short Form-36 scores. A total of 27 adverse events were
      reported in 15 patients (22.7%), with most of them being mild in intensity
      (70.4%). The rates of the adverse events were similar in the monotherapy and
      combination therapy groups (peginterferon alfa-2a + lamivudine, peginterferon
      alfa-2a + adefovir or peginterferon alfa-2a + entecavir therapy groups), at 23.7%
      and 14.3%, respectively. The dosage of peginterferon had to be reduced in 3
      patients (4.5%) due to thrombocytopenia. Overall patient compliance to treatment
      was detected as 85.9%. CONCLUSIONS: Based on the lack of serious adverse events
      and absence of impairment in Quality of Life, peginterferon alfa-2a (40KD, 180
      MUg/week, subcutaneously) treatment for 48 weeks led to a high level of patient
      compliance and was associated with a high degree of safety and tolerability for
      the treatment of adult patients with chronic hepatitis B in real-life practice.

PMID- 23161302
TI  - Pegylated interferon-based treatment in patients with advanced liver disease due
      to chronic delta hepatitis.
AB  - BACKGROUND/AIMS: The safety and efficacy of interferons in advanced delta
      hepatitis have not been explored. The aim of this subanalysis of a multicenter
      clinical trial was to compare the efficacy and safety of 48 weeks of pegylated
      interferon alpha-2a (180 MUg weekly) with or without adefovir (10 mg daily) in
      patients with chronic delta hepatitis-induced advanced liver disease and in those
      with non-advanced liver disease. MATERIALS AND METHODS: Thirty-one patients with
      advanced and 27 patients with non-advanced liver disease were assessed. Patients
      were considered to have advanced liver disease when biopsy disclosed a fibrosis
      score of >=4 according to Ishak or when imaging studies were indicative of
      cirrhosis. Virologic response, defined as achievement of undetectable hepatitis D
      virus RNA, was assessed at the end of treatment and end of 24 weeks of treatment
      free follow-up. RESULTS: Patients with advanced disease had lower hepatitis D
      virus RNA levels and platelet counts (p=0.014 and p=0.0015, respectively). End of
      treatment and end of follow-up virologic responses in patients with advanced vs.
      non-advanced liver disease were similar (29% vs. 19% and 32% vs 23%). Proportion
      of adverse events did not differ between groups except that thrombocytopenia was
      noted more often in the advanced liver disease group. Further, four cases of
      clinically important adverse events including two cases of hepatic decompensation
      and one case of tuberculosis reactivation occurred in the advanced liver disease
      group. CONCLUSIONS: Pegylated interferon is as effective in patients with
      advanced liver disease due to chronic delta hepatitis as in patients with non
      advanced liver disease, but patients should be monitored closely for clinically
      important side effects.

PMID- 23161303
TI  - Alpha-1 antitrypsin deficiency in patients with chronic hepatitis.
AB  - BACKGROUND/AIMS: Alpha-1 antitrypsin deficiency causes accumulation of mutant
      alpha-1 antitrypsin molecules in hepatocytes, and is attributed to severe liver
      injury even in heterozygous state. However, there is a question as to whether
      alpha-1 antitrypsin deficiency is only a cause of liver injury or has a worsening
      effect on the underlying liver disease. We aimed to determine the role of alpha-1
      antitrypsin deficiency in the ongoing chronic hepatitic process. MATERIALS AND
      METHODS: Fifty-four patients with the diagnosis of chronic hepatitis by liver
      biopsy (36 chronic hepatitis B virus, 8 chronic hepatitis C virus, 7 non
      alcoholic steatohepatitis, 2 primary biliary cirrhosis, and 1 autoimmune
      hepatitis) and 51 age- and sex-matched control subjects chosen from among healthy
      blood donors were included in the study. Isoelectric focusing for identifying
      alpha-1 antitrypsin phenotypes was performed in all patients and control
      subjects, whereas the histopathological examination was done only in patients.
      RESULTS: Alpha-1 antitrypsin-deficient variant was absent in patients and
      controls. The mean serum alpha-1 antitrypsin level was significantly lower in
      patients (157.4 +/- 33 mg/dl) than controls (134.8 +/- 30 mg/dl) (p<0.00).
      Histological activity index and fibrosis grade in the liver were not related to
      the serum alpha-1 antitrypsin level (p: 0.276 and 0.902, respectively).
      Additionally, the serum alpha-1 antitrypsin levels among normal variants of alpha
      1 antitrypsin did not differ according to the underlying liver diseases (p:
      0.928). CONCLUSIONS: This prospective case-control study could not define any
      additional effect of alpha-1 antitrypsin deficiency on liver histopathology in
      chronic hepatitis patients.

PMID- 23161304
TI  - Risk factors for higher anti-HCV positivity in a border city in southern Turkey
      with unique population characteristics.
AB  - BACKGROUND/AIMS: This study was conducted as a seroprevalence study on hepatitis
      C virus infection in a small city located in southern Anatolia, to estimate the
      prevalence of hepatitis C virus and to explore the potential risk factors for
      hepatitis C virus infection at this population level. MATERIAL AND METHODS: A
      total of 1427 (685 male (48%), 742 female) subjects agreed to participate in the
      study. Risk factors were examined using a questionnaire. All blood samples were
      tested using third-generation anti-hepatitis C virus enzyme-linked immunosorbent
      assays. RESULTS: The overall anti-hepatitis C virus prevalence was 3.1%
      (44/1427). There was a steady rise in the prevalence of anti-hepatitis C virus
      positivity with age; the anti-hepatitis C virus prevalence was slightly higher in
      men (3.6%) than women (2.6%). The prevalence of anti-hepatitis C virus positivity
      was significantly higher in primary school graduates (3.4%) (odds ratio [OR]:
      4.1, 95% confidence interval [CI]: 1.5-11.6, p=0.0001) and in illiterate subjects
      (5.0%) (OR: 2.7, 95% CI: 1.1-7.4, p=0.021) compared to secondary-plus graduates.
      Anti-hepatitis C virus positivity was higher (3.7%) in married subjects (OR: 8.7,
      95% CI: 1.2-63.7, p=0.003) compared to single subjects (0.0%). Having dental
      procedure, delivery at home, provocative abortion, working abroad, hypertension,
      and diabetes mellitus were factors found to increase the anti-hepatitis C virus
      positivity significantly. CONCLUSIONS: In the region of the current study, the
      anti-hepatitis C virus seroprevalence was higher compared to the whole country.
      Illiteracy, previous dental procedures, and working abroad in neighboring
      countries seem to be factors that relate to this high ratio.

PMID- 23161306
TI  - A case of eosinophilic gastroenteritis mimicking gastric lymphoma associated with
      pancreatitis due to duodenal involvement.
AB  - A case of eosinophilic gastroenteritis is reported in a 17-year-old woman. The
      disease has the signs of delayed gastric emptying, vomiting, weight loss, and
      substantial thickening of the gastric antrum. Histopathology established the
      diagnosis of eosinophilic gastroenteritis of panmural type. Improvement in the
      patient's symptoms and laboratory parameters was observed with steroid treatment.
      The clinicopathological features of this disease are summarized in the
      discussion.

PMID- 23161305
TI  - Endosonography and magnetic resonance cholangiopancreatography show similar
      efficacy in selecting patients for ERCP in mild-moderate acute biliary
      pancreatitis.
AB  - BACKGROUND/AIMS: We aimed to compare the value of endoscopic ultrasonography and
      magnetic resonance cholangiopancreatography in identifying the patients with mild
      moderate acute biliary pancreatitis who require endoscopic retrograde
      cholangiopancreatography. MATERIAL AND METHODS: The study was prospectively
      conducted in a tertiary hospital between June 2006 and October 2009. Ninety-five
      patients without urgent endoscopic retrograde cholangiopancreatography
      requirement and with mild-moderate acute biliary pancreatitis were included in
      the study. Patients whose amylase, C-reactive protein, and bilirubin levels had
      decreased more than 50% on the fifth day compared to admission levels were
      randomized to magnetic resonance cholangiopancreatography or endoscopic
      ultrasonography, and the common bile duct was evaluated. Endoscopic retrograde
      cholangiopancreatography was performed in patients with stone detected with
      endoscopic ultrasonography or magnetic resonance cholangiopancreatography. With
      regard to the presence of common bile duct stone in endoscopic retrograde
      cholangiopancreatography, endoscopic retrograde cholangiopancreatography
      performances were classified as therapeutic or diagnostic. RESULTS: Endoscopic
      retrograde cholangiopancreatography was performed in 16 of the 48 patients
      (33.3%) in the endoscopic ultrasonography group and in 18 of the 47 patients
      (38%) in the magnetic resonance cholangiopancreatography group. Therapeutic
      endoscopic retrograde cholangiopancreatography was performed in 14/16 patients
      (87%) in the endoscopic ultrasonography group and in 16/18 patients (88%) in the
      magnetic resonance cholangiopancreatography group. The ratio of total number of
      endoscopic retrograde cholangiopancreatographis was not significantly lower in
      the endoscopic ultrasonography (16/48) than in the magnetic resonance
      cholangiopancreatography (18/47) group, and the ratio of therapeutic endoscopic
      retrograde cholangiopancreatographis (14/16) was not higher in the endoscopic
      ultrasonography group than in the magnetic resonance cholangiopancreatography
      group (16/18). CONCLUSIONS: The necessity of therapeutic endoscopic retrograde
      cholangiopancreatography was determined with similar efficacy by endoscopic
      ultrasonography and magnetic resonance cholangiopancreatography in mild-moderate
      acute biliary pancreatitis.

PMID- 23161307
TI  - A case of ulcerative colitis complicated with bronchiolitis obliterans organizing
      pneumonia (BOOP) and air leak syndrome.
AB  - Extraintestinal manifestations of inflammatory bowel diseases are well recognized
      and mainly affect the joints, skin, liver, and eyes; however, clinically
      significant pulmonary involvement is very rare. Early identification of pulmonary
      involvement is important and will be life-saving. We report herein a case of an
      ulcerative colitis patient, presenting with acute respiratory distress syndrome
      and bilateral recurring pneumothorax, pneumomediastinum and subcutaneous
      emphysema, i.e., air leak syndrome. He was diagnosed with open lung biopsy as
      bronchiolitis obliterans organizing pneumonia most probably due to viral etiology
      and responded well to steroid therapy, with almost complete resolution of
      radiographic and clinical findings. In inflammatory bowel disease patients,
      bronchiolitis obliterans organizing pneumonia developing due to viral or fungal
      infectious etiology or due to the inflammatory bowel disease itself may progress
      to acute respiratory distress syndrome and may present with air leak syndrome.
      Early detection is important and life-saving, since bronchiolitis obliterans
      organizing pneumonia often responds well to steroid treatment provided an
      infectious etiology has been excluded or adequate antimicrobial therapy has
      already been initiated.

PMID- 23161308
TI  - Spontaneous splenic infarction in an elderly cirrhotic patient with multiple
      comorbidities.
AB  - Spontaneous splenic infarction has been seen rarely in cirrhosis and portal
      hypertension. The clinical presentation can mimic other causes of acute abdominal
      pain. The diagnosis of the condition is based on clinical findings and splenic
      imaging. In recent years, ultrasonography and computed tomographic scan have
      gained in popularity for the diagnosis of splenic infarction. Most reported cases
      are of focal infarction, and treatment is mostly conservative. Herein, we
      describe a rare case of spontaneous splenic infarction in an elderly cirrhotic
      patient with portal hypertension who also had comorbidities. A 72-year-old female
      previously diagnosed with cirrhosis was admitted for left upper quadrant
      abdominal pain for two days. Her medical history included cryptogenic cirrhosis,
      congestive heart failure, chronic obstructive pulmonary disease, and
      hypertension. Physical examination on admission revealed a palpable splenomegaly.
      Abdominal ultrasonography revealed splenomegaly and a hypoechoic area with
      lobulated contours measuring 62 x 35 mm extending from the subcapsular area to
      the hilus in the middle section of the spleen. Abdominal computed tomographic
      showed a subcapsular hypodense lesion of the spleen measuring 64 x 58 mm. Doppler
      ultrasound revealed a wedge-shaped heterogeneous hypoechoic avascular area
      extending from the central zone to the lateral zone of the spleen. In our case,
      diagnosis of splenic infarction was made by computed tomographic and Doppler
      ultrasonography. Our patient received conservative treatment for the underlying
      diseases. Spontaneous splenic infarction must be kept in mind in cirrhotic
      patients with underlying comorbidities presenting with left upper quadrant pain.

PMID- 23161309
TI  - Cyclosporine rescue therapy in autoimmune liver cirrhosis: a case report.
AB  - Autoimmune hepatitis is an inflammatory condition of the liver that can lead to
      significant morbidity and mortality. Corticosteroids with or without azathioprine
      have been shown to improve outcome and are the current standard of care in
      autoimmune hepatitis patients. However, long-term use of corticosteroids and use
      of azathioprine could be associated with significant adverse effects that prevent
      their continued use at optimal dosages or may even require complete cessation. We
      present a patient with autoimmune liver cirrhosis who was intolerant of
      corticosteroid and azathioprine, who was successfully treated with cyclosporine.
      To our knowledge, cyclosporine use has not been reported previously in autoimmune
      cirrhosis, although it has been used in autoimmune hepatitis patients with
      reported success and good tolerability. We conclude that cyclosporine seems to be
      an effective alternative to azathioprine as a steroid-sparing agent in both non
      cirrhotic and cirrhotic autoimmune hepatitis.

PMID- 23161310
TI  - A rare cause of obstructive jaundice: Fasciola hepatica mimicking
      cholangiocarcinoma.
AB  - Fasciola hepatica is an endemic zoonotic disease in Turkey and neighboring
      countries. The usual definitive host is the sheep; humans are accidental hosts in
      the life cycle of the Fasciola. There are two disease stages: the hepatic (acute)
      and biliary (chronic) stages. When the flukes enter the bile ducts, the symptoms
      of cholestasis and cholangitis may present, which can easily be misdiagnosed as
      obstructive jaundice of other causes. We present a case of fascioliasis, which
      was difficult to differentiate from cholangiocarcinoma. A 47-year-old woman from
      Eastern Turkey presented with fever, right upper quadrant abdominal pain, and
      jaundice. Total bilirubin was 4.2 mg/dl, aspartate aminotransferase 55 IU/L,
      alanine aminotransferase 65 IU/L, alkaline phosphatase 325 IU/L, and gamma
      glutamyl transpeptidase 172 IU/L. All tumor markers including carcinoembryonic
      antigen and Ca19-9 were in normal values. After extended evaluation, an
      explorative laparotomy with cholecystectomy, choledochostomy and T-tube drainage
      was performed. Multiple flukes were removed from the choledochus. One of the
      parasites was sent to the parasitological clinic for identification. The result
      of an indirect hemagglutination test for F. hepatica was 1/320 (+). In
      conclusion, the chronic phase of this zoonotic infection can be easily
      misdiagnosed as any other cause of obstructive jaundice. Thus, F. hepatica should
      be considered in the differential diagnosis of common bile duct obstruction,
      especially in endemic areas.

PMID- 23161311
TI  - Associations with hypoglycemia are useful: a case report of Allgrove syndrome.

PMID- 23161312
TI  - Esophageal duplication cyst: a rare cause of back pain.

PMID- 23161313
TI  - Femoral muscle metastasis from gastric carcinoma.

PMID- 23161314
TI  - Isolated left supraclavicular hydatid cyst mimicking Virchow's node.

PMID- 23161315
TI  - Spontaneous intramural jejunal hematoma: two cases.

PMID- 23161316
TI  - Ogilvie's syndrome in sickle cell disease.

PMID- 23161317
TI  - Choreiform movements associated with pegylated interferon-alpha in a patient with
      chronic hepatitis C.

PMID- 23161318
TI  - Clinical remission after strict gluten-free diet in a patient with celiac
      disease, advanced cryptogenic cirrhosis and splenic atrophy.

PMID- 23161319
TI  - An unusual presentation of Seckel syndrome: fatty liver.

PMID- 23161320
TI  - An unusual case of polycythemia vera with a complication of pancreatic
      pseudocyst.

PMID- 23161321
TI  - Prospective validation of the Glasgow Blatchford scoring system in patients with
      upper gastrointestinal bleeding in the emergency department.
AB  - BACKGROUND/AIMS: This study aimed to allow decision-making about hospitalization
      or discharge using the Glasgow Blatchford Scoring system, a risk analysis
      performed using basic laboratory and clinical variables, in patients presenting
      to the Emergency Department with upper gastrointestinal system bleeding.
      MATERIALS AND METHODS: This prospective, observational study conducted in the
      Emergency Department of a university hospital enrolled patients aged >=18 years,
      who presented to the Emergency Department with upper gastrointestinal system
      bleeding between June 2009 and December 2010. For all patients, Glasgow
      Blatchford Scoring scores were calculated, and the patients were classified into
      two groups as high-risk and low-risk patients. RESULTS: A total of 160 subjects
      with upper gastrointestinal system bleeding were enrolled in the study. Mean
      Glasgow Blatchford Scoring scores were 7.1 +/- 3.8 for 71 low-risk subjects and
      11.7 +/- 2.9 for 89 high-risk subjects, and the difference between the two groups
      was statistically significant (p<0.001). When the performance of the Glasgow
      Blatchford Scoring system was evaluated in the determination of high risk, the
      sensitivity and specificity were 100% and 1.41%, respectively, for a cut-off
      value of Glasgow Blatchford Scoring >0, 100% and 16.9% for a cut-off value of
      Glasgow Blatchford Scoring >3, 96.63% and 36.62% for a cut-off value of Glasgow
      Blatchford Scoring >5, and 86.52% and 69.01% for a cut-off value of Glasgow
      Blatchford Scoring >8. In the receiver operating characteristic curve analysis,
      for Glasgow Blatchford Scoring in the high-risk estimation, the area under the
      curve was found to be 0.82 (95% CI: 0.75-0.88), and this value was statistically
      significant (p=0.0001). CONCLUSIONS: The Glasgow Blatchford Scoring system, which
      may be easily calculated based on laboratory and clinical variables, seems to be
      a useful scoring system for risk analysis of all patients with upper
      gastrointestinal system bleeding admitted to the Emergency Department.

PMID- 23161322
TI  - Assessment of COX-2 expression presence and severity by immunohistochemical
      method in patients with chronic active gastritis and intestinal metaplasia.
AB  - BACKGROUND/AIMS: The risk of gastric cancer is increased in patients with
      intestinal metaplasia. Cyclooxygenase-2 activity is crucial for gastric cancer
      cell survival and proliferation. We aimed to assess cyclooxygenase-2 expression
      in patients with intestinal metaplasia or chronic active gastritis and in
      patients with or without a family history of gastric cancer, i.e. a first-degree
      relative with gastric cancer. MATERIALS AND METHODS: One hundred and six patients
      with histologically proven intestinal metaplasia, chronic active gastritis or
      normal gastric mucosa were included. Immunohistochemical staining was performed
      using the immunoperoxidase method. RESULTS: Cyclooxygenase-2 expression was
      detected in 23.1% of normal gastric mucosa, 70.6% of chronic active gastritis,
      and 90.5% of intestinal metaplasia patients. Cyclooxygenase-2 expression was
      significantly higher in intestinal metaplasia than in chronic active gastritis
      (p=0.018). Cyclooxygenase-2 expression was significantly more severe in the
      intestinal metaplasia group when compared to the chronic active gastritis group
      (p=0.017). Severe cyclooxygenase-2 expression (>60% of cells) was more frequent
      in the intestinal metaplasia group. Cyclooxygenase-2 expression was higher in the
      Helicobacter pylori-positive group when compared to the Helicobacter pylori
      negative group (80.3% vs 57.1%, respectively; p=0.012). Cyclooxygenase-2
      expression did not significantly differ according to presence of a first-degree
      relative with gastric cancer. CONCLUSIONS: Patients with intestinal metaplasia
      demonstrated increased presence and severity of cyclooxygenase-2 expression. Our
      findings suggest that cyclooxygenase-2 plays an important role in the stepwise
      process that eventually leads to gastric cancer. There was no statistically
      significant difference between the patients with and without a first-degree
      relative with a history of gastric cancer in terms of cyclooxygenase-2
      expression.

PMID- 23161323
TI  - Isolated positive anti-gliadin immunoglobin-A antibody in children with
      gastrointestinal symptoms.
AB  - BACKGROUND/AIMS: The use of immunoglobulin G and A anti-gliadin antibodies for
      celiac disease screening has decreased due to higher specificity and sensitivity
      of tissue transglutaminase and endomysial antibodies. Greater values of
      immunoglobulin-A anti-gliadin antibody have been associated with more severe
      mucosal damage in proven and probable celiac disease patients. The aim of this
      study was to determine whether anti-gliadin antibody immunoglobulin A has any
      clinical importance in diagnosing celiac disease in children. Children with a
      chronic history of vomiting, abdominal pain, diarrhea, or constipation in the
      outpatient clinic were evaluated for celiac disease. MATERIALS AND METHODS:
      Tissue transglutaminase and anti-gliadin antibody immunoglobulin A in serum were
      determined by ELISA test and endomysial antibodies immunoglobulin A by indirect
      immunofluorescence. Most of these children with isolated positive anti-gliadin
      antibody immunoglobulin A were further evaluated by performing proximal
      gastrointestinal biopsies. RESULTS: Sixteen children had isolated positive anti
      gliadin antibody immunoglobulin A (negative tissue transglutaminase and
      endomysial antibodies immunoglobulin A). Eight were male (mean age: 9.7 years).
      None had immunoglobulin A deficiency. Thirteen underwent an upper endoscopy with
      multiple small bowel biopsies. Two patients had villous atrophy and slightly
      increased intraepithelial lymphocytes (Marsh 3a), which could make the diagnosis
      of celiac disease likely. These two patients had high titers of anti-gliadin
      antibody immunoglobulin A above 70 Units. CONCLUSIONS: An isolated positive
      antigliadin antibody immunoglobulin A result in the absence of positive tissue
      transglutaminase and endomysial antibodies immunoglobulin A should raise the
      suspicion of the diagnosis of celiac disease. This could be a non-specific
      phenomenon that could be found in other gastrointestinal conditions, latent
      celiac disease, or gluten hypersensitivity. A longitudinal clinical follow-up is
      recommended in these children to confirm the diagnosis.

PMID- 23161324
TI  - Risk factors for complications after total colectomy in ulcerative colitis.
AB  - BACKGROUND/AIMS: Ulcerative colitis can be cured by total proctocolectomy. The
      aim of this study was to investigate the risk factors for colectomy-related
      complications in ulcerative colitis patients. MATERIALS AND METHODS: All patients
      with ulcerative colitis who underwent total colectomy at Seoul National
      University Hospital from 1990 to 2009 were identified through a surgical
      database. Their demographic and clinical characteristics were reviewed
      retrospectively. They were followed for a mean of 6.2 years, and risk factors
      affecting the development of complications were analyzed. RESULTS: A total of 85
      ulcerative colitis patients (M:F = 35:50) were enrolled and analyzed. Eighty
      (94.1%) patients received total proctocolectomy with ileal pouch-anal
      anastomosis. Thirty-nine (45.9%) patients had readmitted (95 hospitalizations)
      and 23 (27.1%) underwent further surgical procedures (44 operations) due to
      complications. Multivariate analysis showed that female gender (odds ratio [OR],
      2.99; p=0.046), delayed surgery (OR, 3.45; p=0.03), and postoperative
      pathological diagnosis of dysplasia/cancer (OR, 4.22; p=0.03) were the risk
      factors for complication-related rehospitalization. Pouchitis (OR, 6.31; p=0.007)
      and frequent previous ulcerative colitis flare-up (OR, 1.39; p=0.023) were the
      risk factors for complication-related reoperation. CONCLUSIONS: Female gender,
      delayed surgery, pathological diagnosis of dysplasia/cancer, pouchitis, and
      frequent previous flare-up are the risk factors for postoperative complications.

PMID- 23161325
TI  - Recent advances in preparation and application of hybrid organic-silica
      monolithic capillary columns.
AB  - Hybrid organic-silica monolithic columns, regarded as a second generation of
      silica-based monoliths, have received much interest due to their unique
      properties over the pure silica-based monoliths. This review mainly focuses on
      development in the fields of preparation of hybrid monolithic columns in a
      capillary and their application for CEC and capillary liquid chromatography
      separation, as well as for sample pretreatment of solid-phase microextraction and
      immobilized enzyme reactor since July 2010. The preparation approaches are
      comprehensively summarized with three routes: (i) general sol-gel process using
      trialkoxysilanes and tetraalkoxysilanes as coprecursors; (ii) "one-pot" process
      of alkoxysilanes and organic monomers concomitantly proceeding sol-gel chemistry
      and free radical polymerization; and (iii) other polymerization approaches of
      organic monomers containing silanes. The modification of hybrid monoliths
      containing reactive groups to acquire the desired surface functionality is also
      described.

PMID- 23161326
TI  - Making the case for IPS supported employment.
AB  - Individual Placement and Support (IPS) is an evidence-based practice for helping
      people with severe mental illness (SMI) gain competitive employment, yet those
      who could benefit often find it difficult to obtain IPS services. We summarize
      the evidence supporting the effectiveness of IPS and the benefits of working,
      discuss the barriers to implementing IPS in the U.S., and suggest policy changes
      that could expand its access. 

PMID- 23161327
TI  - Health behaviors contribute to quality of life in patients with advanced heart
      failure independent of psychological and medical patient characteristics.
AB  - BACKGROUND: Little is known about the contribution of health behaviors to quality
      of life (QoL) in heart transplant candidates. We examined physical activity,
      dietary habits, psychological, and medical patient characteristics as correlates
      of QoL among patients enrolled in the multisite Waiting for a New Heart Study.
      METHOD: QoL (Minnesota Living with Heart Failure Questionnaire), demographic
      variables, psychological variables (e.g., depression, coping styles), and health
      behaviors (physical activity, dietary habits) were assessed in 318 patients (82%
      male, 53 +/- 11 years) at the time of wait-listing and analyzed in 312 patients
      (excluding six underweight patients). Eurotransplant provided BMI and medical
      variables to compute the Heart Failure Survival Score (HFSS). Hierarchical
      multiple regression models were used to assess the independent contribution of
      health behaviors to QoL. RESULTS: The HFSS was unrelated to QoL. As expected,
      psychological characteristics (depression, anxiety, vigilant coping style)
      contributed to impaired QoL, accounting for 22.9, 35.9, and 12.9% of the variance
      in total, emotional, and physical QoL, respectively. Physical inactivity further
      impaired QoL (total: 4.1%, p < 0.001; physical: 7.4%, p < 0.001). Dietary habits
      typically considered as unhealthy (i.e., infrequent consumption of
      fruits/vegetables/legumes; frequent intake of foods high in saturated fats) were
      related to enhanced physical QoL, but only among the overweight and obese
      patients. CONCLUSION: Lifestyle interventions to modify negative emotions and to
      increase physical activity could help to improve QoL in heart transplant
      candidates, regardless of their disease severity. The role of eating habits in
      QoL among obese and overweight patients needs further exploration.

PMID- 23161328
TI  - Relationship between implantation of missing anterior teeth and oral health
      related quality of life.
AB  - PURPOSE: The aim of the present study was to investigate the relationship between
      anterior teeth implantation and oral health-related quality of life (OHRQoL).
      METHODS: Participants completed the Chinese version of the Oral Health Impact
      Profile-14 (OHIP-14) prior to implantation and at 6 months following crown
      restoration. Participant demographic information was recorded. Six months
      following implant crown restoration, participants were asked to self-assess their
      overall oral health and implant restoration. A Kruskal-Wallis test and Spearman
      correlation test were used for statistical analyses. A p value <0.05 was
      considered statistically significant. RESULTS: A total of 238 patients (133 women
      and 105 men) completed the study. OHP-14 scores were negatively correlated with
      self-assessment of both overall oral health (r = -0.788, p < 0.001) and implant
      restoration (r = -0.739, p < 0.001) after implant crown restoration. There were
      no significant differences between qualitative reasons for dissatisfaction or
      between quantity of reasons given for dissatisfaction (p = 0.845). Six months
      following crown restoration, the overall OHIP-14 scores and the four common
      factors (disability, psychological discomfort, functional limitation, pain, and
      discomfort) decreased significantly compared to preimplantation scores (p <
      0.001). From the paired differences between genders before and after
      implantation, significant differences were observed in overall quality (p =
      0.044) and disability (p = 0.029). Patients with a higher education level scored
      significantly higher on overall quality of life (p = 0.031) and psychological
      discomfort (p = 0.002) following crown restoration. CONCLUSIONS: Our findings
      indicate that the implantation of anterior missing teeth could significantly
      improve patient OHRQoL. Gender and education level were shown to affect
      implantation results.

PMID- 23161329
TI  - Functional status, life-space mobility, and quality of life: a longitudinal
      mediation analysis.
AB  - PURPOSE: Using the Wilson-Cleary model of patient outcomes as a conceptual
      framework, the impact of functional status on health-related quality of life
      (HRQoL) among older adults was examined, including tests of the mediation
      provided by life-space mobility. METHODS: Participants were enrollees in a
      population-based, longitudinal study of mobility among community-dwelling older
      adults. Data from four waves of the study equally spaced approximately 18 months
      apart (baseline, 18, 36, and 54 months) were used for participants who survived
      at least 1 year beyond the 54-month assessment (n = 677). Autoregressive
      mediation models using longitudinal data and cross-sectional mediation models
      using baseline data were evaluated and compared using structural equation
      modeling. RESULTS: The longitudinal autoregressive models supported the mediating
      role of life-space mobility and suggested that this effect is larger for the
      mental component summary score than the physical component summary score of the
      SF-12. Evidence for a reciprocal relationship over time between functional
      status, measured by ADL difficulty, and life-space mobility was suggested by
      modification indices; these model elaborations did not alter the substantive
      meaning of the mediation effects. Mediated effect estimates from longitudinal
      autoregressive models were generally larger than those from cross-sectional
      models, suggesting that mediating relationships would have been missed or were
      potentially underestimated in cross-sectional models. CONCLUSIONS: These results
      support a mediating role for life-space mobility in the relationship between
      functional status and HRQoL. Functional status limitations might cause diminished
      HRQoL in part by limiting mobility. Mobility limitations may precede functional
      status limitations in addition to being a consequence thereof.

PMID- 23161330
TI  - Measurement issues in the evaluation of chronic disease self-management programs.
AB  - OBJECTIVES: To provide an in-depth analysis of outcome measures used in the
      evaluation of chronic disease self-management programs consistent with the
      Stanford curricula. METHODS: Based on a systematic review on self-management
      programs, effect sizes derived from reported outcome measures are categorized
      according to the quality of life appraisal model developed by Schwartz and Rapkin
      which classifies outcomes from performance-based measures (e.g., clinical
      outcomes) to evaluation-based measures (e.g., emotional well-being). RESULTS: The
      majority of outcomes assessed in self-management trials are based on evaluation
      based methods. Overall, effects on knowledge--the only performance-based measure
      observed in selected trials--are generally medium to large. In contrast,
      substantially more inconsistent results are found for both perception- and
      evaluation-based measures that mostly range between nil and small positive
      effects. CONCLUSIONS: Effectiveness of self-management interventions and
      resulting recommendations for health policy makers are most frequently derived
      from highly variable evaluation-based measures, that is, types of outcomes that
      potentially carry a substantial amount of measurement error and/or bias such as
      response shift. Therefore, decisions regarding the value and efficacy of chronic
      disease self-management programs need to be interpreted with care. More research,
      especially qualitative studies, is needed to unravel cognitive processes and the
      role of response shift bias in the measurement of change.

PMID- 23161331
TI  - Physical activity and quality of life in older adults: an 18-month panel
      analysis.
AB  - PURPOSE: Although physical activity has been associated with quality of life
      (QOL), the empirical evidence regarding the mechanisms underlying this
      relationship is limited. In the present study, we examined the mediating roles
      played by self-efficacy and health status in the physical activity-QOL
      relationship from baseline to 18-month follow-up in a sample of community
      dwelling older adults. METHODS: Community-dwelling adults (N = 321, M age = 63.8
      years) were recruited to participate in a cross-sectional study and were later
      contacted to participate in an 18-month follow-up. Individuals completed a
      battery of questionnaires assessing physical activity, self-efficacy, physical
      self-worth, disability limitations, and quality of life. A panel analysis within
      a covariance modeling framework was used to analyze the data. RESULTS: Overall,
      the model was a good fit to the data (chi(2) = 61.00, df = 29, p < 0.001,
      standardized root mean residual = 0.05, Comparative Fit Index = 0.97) with
      changes in physical activity indirectly influencing change in life satisfaction
      from baseline to 18 months via changes in exercise self-efficacy, physical self
      worth, and disability limitations independent of baseline relationships and
      demographic factors. Specifically, increases in physical activity were associated
      with increases in exercise self-efficacy which, in turn, was associated with
      higher physical self-worth and fewer disability limitations which were associated
      with greater life satisfaction. CONCLUSIONS: The findings from this study suggest
      the relationship between physical activity and global QOL in older adults may be
      mediated by more proximal modifiable outcomes that can be targeted in physical
      activity programs and interventions.

PMID- 23161332
TI  - Compound screening platform using human induced pluripotent stem cells to
      identify small molecules that promote chondrogenesis.
AB  - Articular cartilage, which is mainly composed of collagen II, enables smooth
      skeletal movement. Degeneration of collagen II can be caused by various events,
      such as injury, but degeneration especially increases over the course of normal
      aging. Unfortunately, the body does not fully repair itself from this type of
      degeneration, resulting in impaired movement. Microfracture, an articular
      cartilage repair surgical technique, has been commonly used in the clinic to
      induce the repair of tissue at damage sites. Mesenchymal stem cells (MSC) have
      also been used as cell therapy to repair degenerated cartilage. However, the
      therapeutic outcomes of all these techniques vary in different patients depending
      on their age, health, lesion size and the extent of damage to the cartilage. The
      repairing tissues either form fibrocartilage or go into a hypertrophic stage,
      both of which do not reproduce the equivalent functionality of endogenous hyaline
      cartilage. One of the reasons for this is inefficient chondrogenesis by
      endogenous and exogenous MSC. Drugs that promote chondrogenesis could be used to
      induce self-repair of damaged cartilage as a non-invasive approach alone, or
      combined with other techniques to greatly assist the therapeutic outcomes. The
      recent development of human induced pluripotent stem cell (iPSCs), which are able
      to self-renew and differentiate into multiple cell types, provides a potentially
      valuable cell resource for drug screening in a "more relevant" cell type. Here we
      report a screening platform using human iPSCs in a multi-well plate format to
      identify compounds that could promote chondrogenesis.

PMID- 23161333
TI  - Real-time monitoring of thermodynamic microenvironment in a pan coater.
AB  - The current study demonstrates the use of tablet-size data logging devices
      (PyroButtons) to quantify the microenvironment experienced by tablets during pan
      coating process. PyroButtons were fixed at the inlet and exhaust plenums, and
      were also placed to freely move with the tablets. The effects of process
      parameters (spray rate and inlet-air humidity) on the thermodynamic conditions
      inside the pan coater were studied. It was shown that the same exhaust
      temperature (a parameter most commonly monitored and controlled during film
      coating) can be attained with very different tablet-bed conditions. The tablet
      bed conditions were found to be more sensitive to the changes in spray rate as
      compared with the inlet-air humidity. Both spray rate and inlet-air humidity were
      shown to have an effect on the number of tablet defects (loss of logo
      definition), and a good correlation between number of tablet defects and tablet
      bed humidity was observed. The ability to quantify the thermodynamic
      microenvironment experienced by the tablets during coating and be able to
      correlate that to macroscopic tablet defects can be an invaluable tool that can
      help to establish a process design space during product development.

PMID- 23161334
TI  - Phase I study of pulsatile 3-day administration of afatinib (BIBW 2992) in
      combination with docetaxel in advanced solid tumors.
AB  - BACKGROUND: A phase I study to assess the maximum tolerated dose (MTD) of a short
      course of afatinib in combination with docetaxel for the treatment of solid
      tumors. METHODS: Patients with advanced solid malignancies received docetaxel 75
      mg/m(2) intravenously on day 1 and oral afatinib once daily on days 2-4, in 3
      week treatment cycles. The afatinib dose was escalated in successive cohorts of 3
      6 patients until dose-limiting toxicity (DLT). The MTD cohort was expanded to 13
      patients. Pharmacokinetic parameters were assessed. RESULTS: Forty patients were
      treated. Afatinib doses were escalated to 160 mg/day in combination with 75
      mg/m(2) docetaxel. Three patients had drug-related DLTs during cycle 1. The MTD
      was defined as 90 mg/day afatinib (days 2-4) with docetaxel 75 mg/m(2). The most
      frequent drug-related adverse events (all grades) were alopecia, diarrhea,
      stomatitis (all 50 %) and rash (40 %, all grade <= 2). Three patients had
      confirmed responses, two patients had unconfirmed responses and nine patients had
      durable stable disease >6 cycles. No pharmacokinetic interaction was observed.
      CONCLUSION: Afatinib 90 mg administered for 3 days after docetaxel 75 mg/m(2) is
      the MTD for this treatment schedule and the recommended phase II/phase III dose.
      This combination showed anti-tumor activity in phase I, with a manageable adverse
      event profile.

PMID- 23161335
TI  - A Phase I, open-label, dose escalation study of afatinib, in a 3-week-on/1-week
      off schedule in patients with advanced solid tumors.
AB  - BACKGROUND: A Phase I study to determine the maximum tolerated dose (MTD) and
      pharmacokinetics of afatinib (BIBW 2992), a novel irreversible ErbB Family
      Blocker, administered orally once daily in a 3-week-on/1-week-off dosing
      schedule. METHODS: Patients with advanced solid tumors received single-agent
      afatinib at 10, 20, 40, 55 or 65 mg/day. Safety, antitumor activity,
      pharmacokinetics and pharmacodynamic modulation of biomarkers were assessed.
      RESULTS: Forty-three patients were enrolled. Dose-limiting toxicities (DLTs)
      occurred in five patients in the dose escalation phase (1/8 at 40 mg/day; 1/6 at
      55 mg/day; 3/6 at 65 mg/day). The MTD was established at 55 mg/day. In the
      expansion cohort at the MTD, 6 patients experienced a DLT in the first 28-day
      treatment period. The most frequent DLT was diarrhea. The most common adverse
      events were diarrhea, rash, nausea, vomiting and fatigue. Overall, the afatinib
      safety profile in a 3-week-on/1-week-off dose schedule was similar to that of our
      daily-continuous schedule. Afatinib displayed dose-dependent pharmacokinetics at
      doses up to and including 55 mg/day, with a terminal half-life suitable for once
      daily dosing. Signs of clinical antitumor activity were observed. In biopsies
      taken from clinically normal forearm skin, afatinib caused a reduced
      proliferation rate, with a concomitant increase in differentiation of epidermal
      keratinocytes. CONCLUSION: Afatinib in a 3-week-on/1-week-off schedule showed a
      good safety profile. The MTD was 55 mg/day, although excess DLTs in the expansion
      cohort indicated that the 40 mg/day dose would have an acceptable safety profile
      for future studies. Dose cohorts between 40 and 55 mg/day were not examined in
      this study.

PMID- 23161336
TI  - Clinical trial design in biosimilar drug development.
AB  - In contrast to most drugs which are chemically synthesized and have a known
      structure, biological drugs are derived from living organisms or their products.
      Biologicals are structurally more complex and unique from chemically synthesized
      small drug molecules because of their larger size and intricate manufacturing
      process. Secondary to their protein structure, they are also more prone to acute
      and chronic immune responses. Biosimilars are intended to offer comparable safety
      and efficacy relative to reference brand biologicals, yet they are not generic
      alternatives to the original compounds and so are currently not considered
      interchangeable. Given their structural complexity, multifaceted manufacturing
      processes and risk for immunogenicity, biosimilars require class-specific
      regulatory approval pathways. Here we seek to provide a general overview of
      clinical trial design in the era of biosimilar drug development. This will
      include a review of the regulatory requirements for clinical trials in Europe and
      the United States, followed by a review of two biosimilars that have recently
      reported results of randomized trials against branded biologicals.

PMID- 23161337
TI  - Adjuvant dependence of APS pathology-related low-affinity antibodies during
      secondary immune response to tetanus toxoid in BALB/c mice.
AB  - One of the established animal models for autoimmune disease antiphospholipid
      syndrome (APS) is TTd hyperimmunization of mice. Tetanus toxoid (TTd) and plasma
      protein beta2GPI share structural homology so that immunization with TTd induces
      appearance of cross-reactive antibodies. In this paper, we have investigated the
      presence and dynamic of fluctuation of specific (anti-TTd) and auto (anti
      beta2GPI) antibodies induced in BALB/c mice during secondary immune response
      after TTd immunization with alhydrogel or glycerol as adjuvants. In addition, we
      followed the induced reproductive pathology as a sign of autoimmune outcome. We
      show undoubtedly adjuvant dependance of (1) level of induced anti-TTd IgG
      antibodies, (2) changes in levels of low-affinity anti-beta2GPI IgG antibodies,
      and (3) change in fecundity and fertility during secondary immune response. These
      findings once more indicate the importance of chosen adjuvants used for
      successful immunization and eventual autoantibody outcome, this time associated
      with the processes involving low affinity, natural antibodies.

PMID- 23161338
TI  - The effect of aerobic exercise on cortical architecture in patients with chronic
      schizophrenia: a randomized controlled MRI study.
AB  - Via influencing brain plasticity, aerobic exercise could contribute to the
      treatment of schizophrenia patients. As previously shown, physical exercise
      increases hippocampus volume and improves short-term memory. We now investigated
      gray matter density and brain surface expansion in this sample using MRI-based
      cortical pattern matching methods. Comparing schizophrenia patients to healthy
      controls before and after 3 months of aerobic exercise training (cycling) plus
      patients playing table football yielded gray matter density increases in the
      right frontal and occipital cortex merely in healthy controls. However,
      respective exercise effects might be attenuated in chronic schizophrenia, which
      should be verified in a larger sample.

PMID- 23161339
TI  - Improving access to specialist multidisciplinary palliative care consultation for
      rural cancer patients by videoconferencing: report of a pilot project.
AB  - PURPOSE: Palliative care (PC) and palliative radiotherapy (RT) consultation are
      integral to the care of patients with advanced cancer. These services are not
      universally available in rural areas, and travel to urban centers to access them
      can be burdensome for patients and families. The objectives of our study were to
      assess the feasibility of using videoconferencing to provide specialist
      multidisciplinary PC and palliative RT consultation to cancer patients in rural
      areas and to explore symptom, cost, and satisfaction outcomes. METHODS: The
      Virtual Pain and Symptom Control and Palliative Radiotherapy Clinic was piloted
      from January 2008 to March 2011. Cancer patients in rural northern Alberta
      attended local telehealth facilities, accompanied by nurses trained in symptom
      assessment. The multidisciplinary team at the Cross Cancer Institute in Edmonton
      was linked by videoconference. Team recommendations were sent to the patients'
      family physicians. Data were collected on referral, clinical, and consultation
      characteristics and symptom, cost, and satisfaction outcomes. RESULTS: Forty-four
      initial consultation and 28 follow-up visits took place. Mean Edmonton Symptom
      Assessment Scale scores for anxiety and appetite were statistically significantly
      improved at the first follow-up visit (p < 0.01 and p = 0.03, respectively).
      Average per visit savings for patients seen by telehealth versus attending the
      CCI were 471.13 km, 7.96 hours, and Cdn $192.71, respectively. Patients and
      referring physicians indicated a high degree of satisfaction with the clinic.
      CONCLUSION: Delivery of specialist multidisciplinary PC consultation by
      videoconferencing is feasible, may improve symptoms, results in cost savings to
      patients and families, and is satisfactory to users.

PMID- 23161340
TI  - The MASCC/ISOO Mucositis Guidelines Update: introduction to the first set of
      articles.

PMID- 23161341
TI  - Development of a CD-MEKC method for investigating the metabolism of tamoxifen by
      flavin-containing monooxygenases and the inhibitory effects of methimazole,
      nicotine and DMXAA.
AB  - A selective and low-cost CD-MEKC method under acidic conditions was developed for
      investigating the N-oxygenation of tamoxifen (TAM) by flavin-containing
      monooxygenases (FMOs). The inhibitory effects of methimazole (MMI), nicotine and
      5,6-dimethylxanthenone-4-acetic acid (DMXAA) on the given FMO reaction were also
      evaluated; 100 mM phosphate buffer (pH 8.6) was used for performing the enzymatic
      reaction and the separation of TAM and its metabolite tamoxifen N-oxide (TNO) was
      obtained with a BGE consisting of 100 mM phosphoric acid solution adjusted to pH
      2.5 with triethanolamine containing 50 mM sodium taurodeoxycholate, 20 mM
      carboxymethyl beta-CD and 20% ACN. The proposed method was applied for the
      kinetics study of FMO1 using TAM as a substrate probe. A Michaelis-Menten
      constant (K(m)) of 164.1 MUM was estimated from the corrected peak area of the
      product, TNO. The calculated value of the maximum reaction velocity (V(max)) was
      3.61 MUmol/min/MUmol FMO1; 50% inhibitory concentration and inhibition constant
      (K(i)) of MMI, the most common alternate substrate FMO inhibitor, were evaluated
      and the inhibitory effects of two other important FMO substrates, nicotine and
      DMXAA, a novel anti-tumour agent, were investigated.

PMID- 23161342
TI  - HBx-dependent activation of Twist mediates STAT3 control of epithelium
      mesenchymal transition of liver cells.
AB  - This study investigated the molecular mechanisms of liver cells with HBx
      expression on epithelium-mesenchymal transition (EMT) change using Western blot
      analysis and Transwell assay to assess EMT-related protein expression and cell
      mobility. Luciferase reporter assay and chromatin immunoprecipitation (ChIP)
      assay were used to test the Twist promoter containing different STAT3 binding
      loci. Electrophoretic mobility band-shift assay (EMSA) was used to detect Twist
      activity. Results showed that HBx expression affected the EMT-related protein
      expression and the cell mobility of liver cancer cells (MHCC97) and liver cells
      (HL-7702) in vitro or in vivo. These proteins exhibited reversed expression to a
      certain extent after Twist inhibition. In addition, the wound-healing capability
      and the mobility of HL-7702/HBx cells were lower than those treated with control
      siRNA. The expressions of p-STAT3 and Twist were positively correlated with HBx
      expression. The second STAT-3 binding sequence in the Twist promoter region of
      the HL-7702/HBx cells was the first locus. Twist activity in the HL-7702/HBx2
      cells was higher than that in HL-7702 cells. Moreover, the activity decreased
      when the cells were treated with HBx-siRNA to inhibit HBx expression, or with
      STAT3 inhibitor to reduce STAT3 activation. Therefore, Twist is essential for the
      regulation of the mobility of liver cells with HBx expression. HBx activates the
      Twist promoter by activating STAT3 and promotes EMT occurrence in liver cells.

PMID- 23161343
TI  - Impact of a multidisciplinary standardized clinical pathway on perioperative
      outcomes in patients with oesophageal cancer.
AB  - BACKGROUND: Defined clinical pathways can contribute to improved outcomes in
      patients undergoing oesophageal cancer surgery. A standardized oesophagectomy
      clinical pathway (SOCP) established at the Virginia Mason Medical Center (VMMC)
      in Seattle, Washington, USA was introduced into the Royal Surrey County Hospital
      (RSCH), Guildford, UK in 2011. The aim of this study was to see whether transfer
      and implementation of an oesophagectomy care pathway could change postoperative
      outcomes significantly. METHODS: Three consecutively accrued study groups were
      examined at the RSCH: patients operated on immediately before the introduction of
      the SOCP (group 1), patients operated on after the introduction of the SOCP but
      not included in the pathway (group 2), and patients managed according to the SOCP
      (group 3). Outcomes were compared with those of patients who had surgery at the
      VMMC between 2009 and 2011 using the SOCP (group 4). RESULTS: There were 12
      patients in each of the first three groups and 74 in group 4. All groups were
      similar with respect to body mass index, medical co-morbidities and clinical
      stage. The median age of patients in group 3 was significantly lower than that in
      group 1, and median American Society of Anesthesiologists score was significantly
      better in group 3 compared with group 4. Following initiation of the SOCP there
      was an increase in immediate extubation (8 of 12 in group 1 versus 12 of 12 in
      group 3) and first-day mobilization (1 of 12 versus 12 of 12 respectively), and a
      reduction in complications (9 of 12 versus 4 of 12), length of critical care stay
      (4 (range 2-20) days in group 1 versus 3 (1-5) days in group 3) and length of
      hospital stay (17 (12-30) to 7 (6-37) days respectively). Patients not on the
      pathway but who had surgery during the same interval experienced small but non
      significant improvements in length of critical care and hospital stay, and in
      first-day mobilization. CONCLUSION: The study demonstrated improvement in short
      term outcomes after oesophagectomy following the adoption of an established
      multidisciplinary standardized postoperative pathway.

PMID- 23161344
TI  - Infection with high-risk HPV types among female sex workers in northern Vietnam.
AB  - Vaccines against two high-risk human papillomavirus (HPV) types, HPV-16, and HPV
      18, are in use currently, with high efficacy for preventing infections with these
      HPV types and consequent cervical cancers. However, circulating HPV types can
      vary with geography and ethnicity. The aim of this study was to investigate the
      prevalence of HPV types and the association between HPV types and abnormal
      cervical cytology among female sex workers in Northern Vietnam. Cervical swabs
      and plasma samples were collected from 281 female sex workers at two health
      centers in Hanoi and Hai Phong in 2009. The HPV L1 gene was amplified by PCR
      using original and modified GP5(+)/6(+) primers. Amplified PCR products were
      genotyped by the microarray system GeneSquare (KURABO) and/or clonal sequencing.
      Of the 281 women, 139 (49.5%) were positive for HPV DNA. Among the HPV-positive
      samples, 339 strains and 29 different types were identified. Multiple-type and
      high risk-type HPV infections were found in 85 (61.2%) and 124 (89.2%) women,
      respectively. The most common genotype was HPV-52, followed by HPV-16, HPV-18,
      and HPV-58. Abnormal cervical cytology was detected in 3.2% (9/281) of the women,
      and all of these samples were positive for HPV-DNA. Age <=25 years and infection
      with human immunodeficiency virus were associated positively with HPV infection
      among the women while ever smoking was associated negatively. These results show
      that HPV-52 is most prevalent among female sex workers in Northern Vietnam, most
      of whom had normal cervical cytology. This information may be important for
      designing vaccination strategies in Vietnam.

PMID- 23161346
TI  - Butyl methacrylate based monoliths with different cross-linking agents using DMF
      aqueous buffer as porogen.
AB  - A simple porogen containing only DMF and aqueous buffer was used for synthesis of
      monolithic stationary media for CEC). Butyl methacrylate (BMA)-based capillary
      monoliths were obtained using proposed porogen together with acrylic/methacrylic
      cross-linking agents with different alkyl chain lengths. For this purpose,
      ethylene glycol dimethacrylate, butanediol dimethacrylate and hexanediol
      diacrylate (HDDA) were used. The monoliths with better electrochromatographic
      separation performance were obtained when the acrylic cross-linking agent with
      the longest alkyl chain length (i.e. HDDA) was used with the proposed porogen.
      The electrochromatographic separation of alkylbenzenes, phenols and benzoic acids
      were sucessfully performed in CEC particularly using poly(BMA-co-HDDA) monolithic
      stationary phase with the column efficiency up to 270 000 plates/m.

PMID- 23161345
TI  - Clinical and biochemical effects of diode laser as an adjunct to nonsurgical
      treatment of chronic periodontitis: a randomized, controlled clinical trial.
AB  - The aim of this randomized, parallel, controlled clinical trial was to examine
      the clinical and biochemical efficacy of diode laser as an adjunct to scaling and
      root planing (SRP). Thirty chronic periodontitis patients were randomly assigned
      into two groups to receive SRP alone (control) or SRP followed by diode laser
      (test). Plaque index, gingival index, bleeding on probing, probing depth, and
      clinical attachment level were measured at baseline and at 1, 3, and 6 months
      after treatment. The gingival crevicular fluid levels of interleukin-1beta (IL
      1beta), interleukin-6 (IL-6), interleukin-8 (IL-8), matrix metalloproteinase-1
      (MMP-1), matrix metalloproteinase-8 (MMP-8) and tissue inhibitor matrix
      metalloproteinase-1 (TIMP-1) were analyzed by enzyme-linked immunosorbent assay.
      Test group showed significantly a better outcome compared to the control group in
      full-mouth clinical parameters. MMP-1, MMP-8, and TIMP-1 showed significant
      differences between groups after treatment compared to baseline (p < 0.05). The
      total amount of IL-1beta, IL-6, MMP-1, MMP-8, and TIMP-1 decreased (p < 0.05) and
      IL-8 increased after treatment in both test and control groups (p < 0.05). Diode
      laser provided significant improvements in clinical parameters and MMP-8 was
      significantly impacted by the adjunctive laser treatment at first month providing
      an insight to how lasers can enhance the outcomes of the nonsurgical periodontal
      therapy.

PMID- 23161347
TI  - Perception-production asymmetries in homophone spelling: the unique influence of
      aging.
AB  - OBJECTIVES: This research investigated three potential asymmetries in the
      production and perception of homophone spelling errors: aging, homophone
      dominance, and priming. A homophone spelling error occurs when a contextually
      appropriate word (beet) is replaced with its homophone (e.g., beat glaze). Two
      experiments investigated young and older adults' written production and detection
      of these errors. METHOD: Participants wrote sentences (Experiment 1) or detected
      errors in sentences (Experiment 2) containing a dominant homophone (beat) or
      subordinate homophone (beet). Homophones were preceded by a prime (neat) that
      shared orthography with the contextually inappropriate homophone (beat) or by an
      unrelated control word (fun). RESULTS: Results revealed an aging asymmetry in
      production and detection as a function of dominance. Older adults made more
      errors than young adults when producing dominant homophones but fewer errors in
      producing subordinate homophones. In contrast, older adults consistently made
      fewer errors than young adults when detecting homophone errors. Independent of
      aging, dominance had similar effects on production and detection, with more
      errors on subordinate homophones. Priming had asymmetric effects different from
      aging by increasing errors in production but not detection. DISCUSSION: These
      results suggest aging uniquely dissociates perception and production of homophone
      spelling and demonstrate circumstances under which aging benefits language
      processing.

PMID- 23161348
TI  - Life-course socioeconomic status and obesity among older Singaporean Chinese men
      and women.
AB  - OBJECTIVES: To elucidate the association between life-course socioeconomic status
      (SES) and obesity among older (aged 60 and older) Singaporean Chinese men and
      women. METHODS: Data from the Social Isolation, Health and Lifestyles Survey
      (single-stage stratified random sampling design) was utilized. Obesity (body mass
      index >27.4 kg/m(2)) was assessed for 1,530 men and 2,036 women. Childhood
      (family financial status while growing up), adult (education), and older adult
      (housing type) SES indicators were used to define the accumulation of risk
      (cumulative socioeconomic disadvantage), social mobility (8 trajectories using
      the 3 SES indicators), and sensitive period (independent effect of each SES
      indicator) conceptual models. Association between the 3 life-course SES
      conceptual models and obesity was assessed using logistic regression analysis.
      RESULTS: Among women and men, low childhood SES lowered the odds of obesity. Low
      adult SES increased the odds of obesity only among women. There was no
      association between cumulative socioeconomic disadvantage and obesity. Women
      experiencing upward social mobility had lower odds of obesity relative to both
      those experiencing low SES and high SES through the life-course. DISCUSSION:
      Association of the life-course SES conceptual models with obesity among older
      Singaporeans is different from that reported among younger Western populations,
      suggesting the association to be context specific. The different conceptual
      models complement each other.

PMID- 23161349
TI  - Genetic variation within the Hypodontus macropi (Nematoda: Strongyloidea) complex
      from macropodid marsupial hosts in Australia.
AB  - Genetic variation was investigated in the strongylid nematode Hypodontus macropi
      from macropodid marsupials using the second internal transcribed spacer of
      ribosomal DNA. A total of 547 specimens from ten species of hosts, representing
      all of the known hosts of the parasite, from across the Australian continent was
      examined. Phylogenetic analyses revealed distinct genetic clades in each of
      Macropus agilis, M. dorsalis, M. rufogriseus, M. bicolor, Petrogale persephone,
      Thylogale billardierii and T. stigmatica. A further clade contained all specimens
      from M. robustus and M. rufus, together with two examples of host switching by
      nematodes into M. fuliginosus. The latter clade was subdivided into three
      subclades, one comprising specimens occurring in M. robustus erubescens, M. rufus
      and M. fuliginosus, the second in M. r. woodwardi and the third in M. r. robustus
      suggesting a relationship between the subclades and the subspecies of M.
      robustus. The extent of the genetic differences and the fact that several of them
      occur in broad sympatry suggests that H. macropi as currently defined
      morphologically may represent as many as ten cryptic species. Limited evidence
      was found for co-speciation between hosts and parasites; rather most
      relationships were better explained by host switching.

PMID- 23161350
TI  - Interobserver reliability of fetal heart rate pattern interpretation using NICHD
      definitions.
AB  - OBJECTIVE: To evaluate the interobserver reliability of fetal heart rate (FHR)
      pattern definition and interpretation assessed by physicians at various levels of
      training using standard Eunice Kennedy Shriver National Institute of Child Health
      and Human Development (NICHD) definitions and standard principles of
      interpretation. STUDY DESIGN: We conducted an interrater reliability study of the
      intrapartum FHR tracings of 32 singleton term pregnancies at Los Angeles County
      University of Southern California (LAC + USC) Medical Center. Analysis included
      the 5 hours immediately preceding delivery, divided into 10- minute segments. A
      medical student, resident, and three attending physicians evaluated the same set
      of FHR tracings. Interobserver agreement was assessed using the free-marginal
      kappa coefficient. RESULTS: Reviewers demonstrated substantial to excellent
      agreement on baseline rate (kappa = 0.97), moderate variability (kappa = 0.80),
      accelerations (kappa = 0.62), decelerations (kappa = 0.63), category (kappa =
      0.68), and the ability to identify the presence of either moderate variability or
      accelerations (kappa = 0.82). CONCLUSIONS: Interobserver agreement was
      significantly higher on all components of FHR definition and interpretation than
      previously expected. Standardization of FHR definitions and interpretation may
      improve interobserver reliability and patient safety.

PMID- 23161351
TI  - Bile acid concentration reference ranges in a pregnant Latina population.
AB  - OBJECTIVE: The total bile acid (TBA) concentration criterion for diagnosing
      intrahepatic cholestasis of pregnancy varies in the published literature. The
      purpose of this study was to establish pregnancy-specific reference ranges for
      the TBA concentration among Latina women. STUDY DESIGN: Self-identified Latina
      women (n = 211) over 18 years of age with a singleton pregnancy were recruited
      and had random serum samples drawn during the second and third trimesters. The
      total and fractionated bile acid concentrations were analyzed by liquid
      chromatography-tandem mass spectrometry (LC-MS/MS), and reference ranges were
      calculated. Laboratory-provided general reference ranges from a general
      population of adult men and nonpregnant women were used for comparison. RESULTS:
      The TBA reference range for our Latina pregnant population (<8.5 umol/L) was
      markedly lower than the laboratory-provided reference range (4.5 to 19.2 umol/L).
      CONCLUSION: These data suggest that the upper TBA concentration reference range
      in our Latina pregnant population is 8.5 umol/L, based on LC-MS/MS measurements.

PMID- 23161352
TI  - The role of microbial communities in parturition: is there evidence of
      association with preterm birth and perinatal morbidity and mortality?
AB  - In 2005, the World Health Organization estimated that 9.6% or 12.9 million births
      worldwide were born preterm at <37 weeks of gestation and were accompanied by a
      mortality rate as high as 42% (http://www.who.int/bulletin/volumes/88/1/08
      062554). Significant data suggesting that intrauterine infection is an important
      modifier for the risk of preterm birth have emerged over the past four decades.
      However, causative microbial culprits have yet to be identified, and
      interventional trials with antimicrobials have uniformly failed to demonstrate a
      significant benefit. To the contrary, treatment for clinically asymptomatic,
      commonly associated polymicrobial communities (i.e., bacterial vaginosis) has
      resulted in an increase in the rate of preterm birth. This article discusses the
      importance of vaginal microbiome and the variance in its composition during
      normal pregnancy. We will expand this discussion to include possible mechanisms
      that might trigger preterm birth in at-risk subjects. Finally, we will review why
      preterm birth may be an ideal forum with which to apply our rapidly expanding
      metagenomic sequencing and analytic pipelines to discern the role of host and
      microbe in the relative continuum of health and disease. 

PMID- 23161353
TI  - Meeting death.

PMID- 23161354
TI  - Open wide.

PMID- 23161355
TI  - Hydrocephalus, agenesis of the corpus callosum, and cleft lip/palate represent
      frequent associations in fetuses with Peters' plus syndrome and B3GALTL
      mutations. Fetal PPS phenotypes, expanded by Dandy Walker cyst and encephalocele.
AB  - OBJECTIVE: Fetal pathology aims to recognize syndromal patterns of anomalies for
      goal-directed mutation analyses, genetic counseling, and early prenatal diagnosis
      in consecutive pregnancies. Here, we report on five fetuses with Peters' plus
      syndrome (PPS) from two distinct families aborted after prenatal ultrasound
      diagnosis of hydrocephaly. METHOD: We performed fetal autopsies and molecular
      analyses. RESULTS: Among 44 fetuses with prenatally diagnosed hydrocephaly, four
      fetuses of 16 to 21 gestational weeks presented with additional cleft lip/palate
      and/or agenesis of the corpus callosum. Other features were growth retardation,
      hypertelorism, anomalies of the eyes, in part consistent with Peters' anterior
      chamber anomalies, mild brachymelia, brachydactyly, and also internal anomalies.
      Suspected PPS was confirmed by detection of B3GALTL mutation in these four
      fetuses and in one additional sib fetus, revealing homozygosity for the common
      c.660 + 1G > A donor splice site mutation in intron 8. CONCLUSIONS: Autosomal
      recessive PPS has not yet been diagnosed prenatally. We want to alert
      ultrasonographers to the diagnosis of this disorder in growth-retarded fetuses
      with (recurrent) hydrocephaly, agenesis of the corpus callosum, and cleft
      lip/palate and stress the more severe fetal manifestation, describing a first
      such case with additional Dandy-Walker cyst and occult meningoencephalocele.

PMID- 23161356
TI  - Psychological impact of unexpected explicit recall of events occurring during
      surgery performed under sedation, regional anaesthesia, and general anaesthesia:
      data from the Anesthesia Awareness Registry.
AB  - BACKGROUND: Anaesthetic awareness is a recognized complication of general
      anaesthesia (GA) and is associated with post-traumatic stress disorder (PTSD).
      Although complete amnesia for intraprocedural events during sedation and regional
      anaesthesia (RA) may occur, explicit recall is expected by anaesthesia providers.
      Consequently, the possibility that there could be psychological consequences
      associated with unexpected explicit recall of events during sedation and RA has
      not been investigated. This study investigated the psychological sequelae of
      unexpected explicit recall of events during sedation/RA that was reported to the
      Anesthesia Awareness Registry. METHODS: The Registry recruited subjects who self
      identified as having had anaesthetic awareness. Inclusion criteria were a patient
      reported awareness experience in 1990 or later and availability of medical
      records. The sensations experienced by the subjects during their procedure and
      the acute and persistent psychological sequelae attributed to this explicit
      recall were assessed for patients receiving sedation/RA and those receiving GA.
      RESULTS: Among the patients fulfilling the inclusion criteria, medical record
      review identified 27 sedation/RA and 50 GA cases. Most patients experienced
      distress (78% of sedation/RA vs 94% of GA). Approximately 40% of patients with
      sedation/RA had persistent psychological sequelae, similar to GA patients. Some
      sedation/RA patients reported an adverse impact on their job performance (15%),
      family relationships (11%), and friendships (11%), and 15% reported being
      diagnosed with PTSD. CONCLUSIONS: Patients who self-reported to the Registry
      unexpected explicit recall of events during sedation/RA experienced distress and
      persistent psychological sequelae comparable with those who had reported
      anaesthetic awareness during GA. Further study is warranted to determine if
      patients reporting distress with explicit recall after sedation/RA require
      psychiatric follow-up.

PMID- 23161357
TI  - Caudal dexmedetomidine combined with bupivacaine inhibit the response to hernial
      sac traction in children undergoing inguinal hernia repair.
AB  - BACKGROUND: Caudal bupivacaine is widely used for inguinal hernia repair in
      children, but often cannot totally eliminate responses to hernial sac traction.
      The current study examined whether supplementation of caudal bupivacaine with
      dexmedetomidine could achieve better results. METHODS: Sixty children aged 12-72
      months undergoing unilateral inguinal hernia repair received standardized
      premedication with midazolam, i.v. ketamine anaesthesia, and then were randomly
      assigned to receive either bupivacaine 0.25% (1 ml kg(-1); Group B) or
      bupivacaine plus dexmedetomidine (1 MUg kg(-1); Group BD). The response to
      hernial sac traction was defined as an increase in heart rate or systolic
      arterial pressure by >20%, and was treated with ketamine rescue (2 mg kg(-1)).
      After the surgery, fentanyl was administered as needed with a nurse-controlled
      analgesia pump. RESULTS: Only one subject in Group BD (3.33%) needed ketamine
      rescue, as opposed to 13 subjects in Group B (43.33%; P<0.001). The first
      fentanyl injection occurred at a much later time point in Group BD (median: 860
      vs 320 min in Group B; P<0.001). Total fentanyl consumption of fentanyl was
      significantly lower in Group BD [2.5 (1.2) vs 6.9 (1.6) MUg kg(-1) 24 h(-1) in
      Group B; P=0.008]. CONCLUSIONS: The addition of dexmedetomidine to caudal
      bupivacaine could reduce the response to hernial sac traction, and prolong the
      duration of postoperative analgesia in children undergoing inguinal hernia
      repair.

PMID- 23161358
TI  - Cross-frequency coupling during isoflurane anaesthesia as revealed by
      electroencephalographic harmonic wavelet bicoherence.
AB  - BACKGROUND: Fourier bicoherence has previously been applied to investigate phase
      coupling in the EEG in anaesthesia. However, there are significant theoretical
      limitations regarding its sensitivity in detecting transient episodes of inter
      frequency coupling. Therefore, we used a recently developed wavelet bicoherence
      method to investigate the cross-frequency coupling in the EEG of patients under
      isoflurane anaesthesia; examining the relationship between the patterns of
      wavelet bicoherence and the isoflurane concentrations. METHODS: We analysed a set
      of previously published EEG data, obtained from 29 patients who underwent
      elective abdominal surgery under isoflurane anaesthesia. Artifact-free, 1 min EEG
      segments at different isoflurane concentrations were extracted from each subject
      and the wavelet bicoherence calculated for all pairs of frequencies from 0.5 to
      20 Hz. RESULTS: Isoflurane caused two peaks in the alpha (6-13 Hz) and slow delta
      (<1 Hz) regions of the bicoherence matrix diagonal. Higher concentrations of
      isoflurane shifted the alpha peak to lower frequencies [11.3 (0.9) Hz at 0.3% to
      7.1 (1.2) Hz at 1.5%], as has been previously observed in the power spectra.
      Outside the diagonal, we also found a significant alpha peak that was phase
      coupled to the slow delta waves; higher concentrations of isoflurane shifted this
      peak to lower frequencies [10.8 (1.2) to 7.7 (0.7) Hz]. CONCLUSIONS: Isoflurane
      caused cross-frequency coupling between alpha and slow delta waves. Increasing
      isoflurane concentration slowed the alpha frequencies where the coupling had
      occurred. This phenomenon of alpha-delta coupling suggests that slow cortical
      oscillations organize the higher alpha band activity, which is consistent with
      other studies in natural sleep.

PMID- 23161359
TI  - Predictive value of pulse pressure variation for fluid responsiveness in septic
      patients using lung-protective ventilation strategies.
AB  - BACKGROUND: The applicability of pulse pressure variation (DeltaPP) to predict
      fluid responsiveness using lung-protective ventilation strategies is uncertain in
      clinical practice. We designed this study to evaluate the accuracy of this
      parameter in predicting the fluid responsiveness of septic patients ventilated
      with low tidal volumes (TV) (6 ml kg(-1)). METHODS: Forty patients after the
      resuscitation phase of severe sepsis and septic shock who were mechanically
      ventilated with 6 ml kg(-1) were included. The DeltaPP was obtained automatically
      at baseline and after a standardized fluid challenge (7 ml kg(-1)). Patients
      whose cardiac output increased by more than 15% were considered fluid responders.
      The predictive values of DeltaPP and static variables [right atrial pressure
      (RAP) and pulmonary artery occlusion pressure (PAOP)] were evaluated through a
      receiver operating characteristic (ROC) curve analysis. RESULTS: Thirty-four
      patients had characteristics consistent with acute lung injury or acute
      respiratory distress syndrome and were ventilated with high levels of PEEP
      [median (inter-quartile range) 10.0 (10.0-13.5)]. Nineteen patients were
      considered fluid responders. The RAP and PAOP significantly increased, and
      DeltaPP significantly decreased after volume expansion. The DeltaPP performance
      [ROC curve area: 0.91 (0.82-1.0)] was better than that of the RAP [ROC curve
      area: 0.73 (0.59-0.90)] and pulmonary artery occlusion pressure [ROC curve area:
      0.58 (0.40-0.76)]. The ROC curve analysis revealed that the best cut-off for
      DeltaPP was 6.5%, with a sensitivity of 0.89, specificity of 0.90, positive
      predictive value of 0.89, and negative predictive value of 0.90. CONCLUSIONS:
      Automatized DeltaPP accurately predicted fluid responsiveness in septic patients
      ventilated with low TV.

PMID- 23161360
TI  - Dexmedetomidine as an adjuvant to ropivacaine prolongs peripheral nerve block: a
      volunteer study.
AB  - BACKGROUND: Dexmedetomidine is an alpha-2-receptor agonist which might be used as
      an additive to local anaesthetics for various regional anaesthetic techniques. We
      therefore designed this prospective, double-blinded, controlled volunteer study
      to investigate the effects of dexmedetomidine as an adjuvant to ropivacaine on
      peripheral nerve block. METHODS: Ultrasound-guided ulnar nerve block (UNB) was
      performed in 36 volunteers with either 3 ml ropivacaine 0.75% (R), 3 ml
      ropivacaine 0.75% plus 20 ug dexmedetomidine (RpD), or 3 ml ropivacaine 0.75%
      plus systemic 20 ug dexmedetomidine (RsD). UNB-related sensory and motor scores
      were evaluated. RESULTS: Sensory onset time of UNB was not different between the
      study groups, whereas motor onset time was significantly faster in Group RpD when
      compared with the other study groups [mean (sd)] [21 (15) vs 43 (25) min in Group
      RsD and 47 (36) min in Group R, P<0.05 Group RpD vs other groups]. The duration
      of sensory block was 350 (54) min in Group R, 555 (118) min in Group RpD, and 395
      (40) min in Group RsD (P<0.01 Group RpD vs other groups, P<0.05 Group RsD vs
      Group R). Motor block duration was similar to the duration of sensory block.
      CONCLUSIONS: A profound prolongation of UNB of ~60% was detected with perineural
      dexmedetomidine when added to 0.75% ropivacaine. The systemic administration of
      20 ug dexmedetomidine resulted in a prolongation of ~10% during UNB with 0.75%
      ropivacaine. Eudra-CT No.: 2012-000030-19.

PMID- 23161361
TI  - The first intravenous anaesthetic: how well was it managed and its potential
      realized?
AB  - Our speciality commonly traces its origin to a demonstration of the inhalation of
      ether by a patient undergoing surgery in Boston in 1846. Less well known is the
      demonstration of the i.v. injection of opium with alcohol into a dog in Oxford in
      1656, leading to anaesthesia followed by full long-term recovery. After gaining
      i.v. access, a mixture of opium and alcohol was injected, resulting in a brief
      period of anaesthesia. After a period during which the dog was kept moving to
      assist recovery, a full recovery was made. Details from this momentous experiment
      allow us to compare the technique used with modern management. It is important to
      consider why there was a failure to translate the results into clinical practice
      and nearly 200 yr of potentially pain-free surgery. Possible factors include lack
      of equipment for i.v. access, lack of understanding of dose-response effects, and
      a climate of scientific discovery rather than clinical application. Given the
      current interest in total i.v. anaesthesia, it seems appropriate to identify its
      origins well before those of inhalation anaesthesia.

PMID- 23161362
TI  - Percutaneous treatment of iatrogenic pseudoaneurysms by cyanoacrylate-based wall
      gluing.
AB  - PURPOSE: Although the majority of iatrogenic pseudoaneurysms (PSAs) are amenable
      to ultrasound (US)-guided thrombin injection, patients with those causing
      neuropathy, claudication, significant venous compression, or soft tissue necrosis
      are considered poor candidates for this option and referred to surgery. We aimed
      to test the effectiveness and feasibility of a novel percutaneous cyanoacrylate
      glue (NBCA-MS)-based technique for treatment of symptomatic and asymptomatic
      iatrogenic PSA. MATERIAL AND METHODS: During a 3-year period, we prospectively
      enrolled 91 patients with iatrogenic PSA [total n = 94 (femoral n = 76; brachial
      n = 11; radial n = 6; axillary n = 1)]. PSA were asymptomatic in 66 % of cases,
      and 34 % presented with symptoms due to neuropathy, venous compression, and/or
      soft tissue necrosis. All patients signed informed consent. All patients received
      NBCA-MS-based percutaneous treatment. PSA chamber emptying was first obtained by
      US-guided compression; superior and inferior walls of the PSA chamber were then
      stuck together using NBCA-MS microinjections. Successfulness of the procedure was
      assessed immediately and at 1-day and 1-, 3-, and 12-month US follow-up. RESULTS:
      PSA occlusion rate was 99 % (93 of 94 cases). After treatment, mean PSA antero
      posterior diameter decrease was 67 +/- 22 %. Neuropathy and vein compression
      immediately disappeared in 91 % (29 of 32) of cases. Patients with tissue
      necrosis (n = 6) underwent subsequent outpatient necrosectomy. No distal
      embolization occurred, nor was conversion to surgery necessary. CONCLUSION: PSA
      treatment by way of NBCA-MS glue injection proved to be safe and effective in
      asymptomatic patients as well as those with neuropathy, venous compression, or
      soft-tissue necrosis (currently candidates for surgery). Larger series are needed
      to confirm these findings.

PMID- 23161363
TI  - Aortic branch artery pseudoaneurysms associated with intramural hematoma: when
      and how to do endovascular embolization.
AB  - PURPOSE: To describe when and how to perform endovascular embolization of aortic
      branch artery pseudoaneurysms associated with type A and type B intramural
      hematoma (IMH) involving the descending thoracic and abdominal aorta (DeBakey I
      and III) that increased significantly in size during follow-up. MATERIALS AND
      METHODS: Sixty-one patients (39 men; mean +/- standard deviation age 66.1 +/-
      11.2 years) with acute IMH undergoing at least two multidetector computed
      tomographic examinations during follow-up for 12 months or longer were enrolled.
      Overall, 48 patients (31 men, age 65.9 +/- 11.5) had type A and type B IMH
      involving the descending thoracic and abdominal aorta (DeBakey I and III).
      RESULTS: Among the 48 patients, 26 (54 %; 17 men, aged 64.3 +/- 11.4 years) had
      71 aortic branch artery pseudoaneurysms. Overall, during a mean follow-up of 22.1
      +/- 9.5 months (range 12-42 months), 31 (44 %) pseudoaneurysms disappeared; 22
      (31 %) decreased in size; two (3 %) remained stable; and 16 (22 %) increased in
      size. Among the 16 pseudoaneurysms with increasing size, five of these (three
      intercostal arteries, one combined intercostobronchial/intercostal arteries, one
      renal artery), present in five symptomatic patients, had a significant increase
      in size (thickness >10 mm; width and length >20 mm). These five patients
      underwent endovascular embolization with coils and/or Amplatzer Vascular Plug. In
      all patients, complete thrombosis and exclusion of aortic pseudoaneurysm and
      relief of back pain were achieved. CONCLUSION: Aortic branch artery
      pseudoaneurysms associated with type A and type B IMH involving the descending
      thoracic and abdominal aorta (DeBakey I and III) may be considered relatively
      benign lesions. However, a small number may grow in size or extend longitudinally
      with clinical symptoms during follow-up, and in these cases, endovascular
      embolization can be an effective and safe procedure.

PMID- 23161364
TI  - p53 acetylation enhances Taxol-induced apoptosis in human cancer cells.
AB  - Microtubule inhibitors (MTIs) such as Taxol have been used for treating various
      malignant tumors. Although MTIs have been known to induce cell death through
      mitotic arrest, other mechanisms can operate in MTI-induced cell death.
      Especially, the role of p53 in this process has been controversial for a long
      time. Here we investigated the function of p53 in Taxol-induced apoptosis using
      p53 wild type and p53 null cancer cell lines. p53 was upregulated upon Taxol
      treatment in p53 wild type cells and deletion of p53 diminished Taxol-induced
      apoptosis. p53 target proteins including MDM2, p21, BAX, and beta-isoform of PUMA
      were also upregulated by Taxol in p53 wild type cells. Conversely, when the wild
      type p53 was re-introduced into two different p53 null cancer cell lines, Taxol
      induced apoptosis was enhanced. Among post-translational modifications that
      affect p53 stability and function, p53 acetylation, rather than phosphorylation,
      increased significantly in Taxol-treated cells. When acetylation was enhanced by
      anti-Sirt1 siRNA or an HDAC inhibitor, Taxol-induced apoptosis was enhanced,
      which was not observed in p53 null cells. When an acetylation-defective mutant of
      p53 was re-introduced to p53 null cells, apoptosis was partially reduced compared
      to the re-introduction of the wild type p53. Thus, p53 plays a pro-apoptotic role
      in Taxol-induced apoptosis and acetylation of p53 contributes to this pro
      apoptotic function in response to Taxol in several human cancer cell lines,
      suggesting that enhancing acetylation of p53 could have potential implication for
      increasing the sensitivity of cancer cells to Taxol.

PMID- 23161365
TI  - Recent progress in analytical capillary isotachophoresis.
AB  - This review brings a survey of the literature on analytical isotachophoresis
      (ITP) from the years 2010-2012. It confirms the fact that ITP alone is not used
      for analyses frequently but that its online combinations with other methods are
      of paramount importance. This review shows that the inherent features of the
      technique and first of all its concentrating ability are still unique for
      reaching high sensitivity and efficient sample cleanup in analytical
      applications. The part devoted to theory is mostly represented by computer
      simulations and confirms the power and significance of this approach. The section
      oriented at instrumentation and techniques shows the advantages of ITP in column
      combinations and microchip techniques. The chapter reviewing the applications is
      categorized according to the techniques applied, viz., column switching, on line
      ITP-CZE and on-chip analyses. The final part of the review is devoted to the
      nearly omnipresent electrophoresis principle of transient isotachophoresis, and
      to the advantages that it may offer for detection and sampling. In all parts, the
      significance of the operational conditions is also considered and where possible,
      the electrolyte system is explicitly presented.

PMID- 23161366
TI  - Improving oxygen conditions in the deeper parts of bornholm sea by pumped
      injection of winter water.
AB  - Vertical diffusivity and oxygen consumption in the basin water, the water below
      the sill level at about 59 m depth, have been estimated by applying budget
      methods to monitoring data from hydrographical stations BY4 and BY5 for periods
      without water renewal. From the vertical diffusivity, the mean rate of work
      against the buoyancy forces below 65 m depth is estimated to about 0.10 mW m(-2).
      This is slightly higher than published values for East Gotland Sea. The
      horizontally averaged vertical diffusivity kappa can be approximated by the
      expression kappa = a 0 N (-1) where N is the buoyancy frequency and a 0 ~ 1.25 *
      10(-7) m(2) s(-2), which is similar to values for a 0 used for depths below the
      halocline in Baltic proper circulation models for long-term simulations. The
      contemporary mean rate of oxygen consumption in the basin water is about 75 g O2
      m(-2) year(-1), which corresponds to an oxidation of 28 g C m(-2) year(-1). The
      oxygen consumption in the Bornholm Basin doubled from the 1970s to the 2000s,
      which qualitatively explains the observed increasing frequency and vertical
      extent of anoxia and hypoxia in the basin water in records from the end of the
      1950s to present time. A horizontally averaged vertical advection-diffusion model
      of the basin water is used to calculate the effects on stratification and oxygen
      concentration by a forced pump-driven vertical convection. It is shown that the
      residence time of the basin water may be reduced by pumping down and mixing the
      so-called winter water into the deepwater. With the present rate of oxygen
      consumption, a pumped flux of about 25 km(3) year(-1) would be sufficient to keep
      the oxygen concentration in the deepwater above 2 mL O2 L(-1). 

PMID- 23161367
TI  - Prevalence of human papillomavirus in women attending cervical screening in the
      UK and Ireland: new data from northern Ireland and a systematic review and meta
      analysis.
AB  - There is substantial international variation in human papillomavirus (HPV)
      prevalence; this study details the first report from Northern Ireland and
      additionally provides a systematic review and meta-analysis pooling the
      prevalence of high-risk (HR-HPV) subtypes among women with normal cytology in the
      UK and Ireland. Between February and December 2009, routine liquid based cytology
      (LBC) samples were collected for HPV detection (Roche Cobas(r) 4800 [PCR]) among
      unselected women attending for cervical cytology testing. Four electronic
      databases, including MEDLINE, were then searched from their inception till April
      2011. A random effects meta-analysis was used to calculate a pooled HR-HPV
      prevalence and associated 95% confidence intervals (CI). 5,712 women, mean age 39
      years (+/-SD 11.9 years; range 20-64 years), were included in the analysis, of
      which 5,068 (88.7%), 417 (7.3%) and 72 (1.3%) had normal, low, and high-grade
      cytological findings, respectively. Crude HR-HPV prevalence was 13.2% (95% CI,
      12.7-13.7) among women with normal cytology and increased with cytological grade.
      In meta-analysis the pooled HR-HPV prevalence among those with normal cytology
      was 0.12 (95% CIs, 0.10-0.14; 21 studies) with the highest prevalence in younger
      women. HPV 16 and HPV 18 specific estimates were 0.03 (95% CI, 0.02-0.05) and
      0.01 (95% CI, 0.01-0.02), respectively. The findings of this Northern Ireland
      study and meta-analysis verify the prevalent nature of HPV infection among
      younger women. Reporting of the type-specific prevalence of HPV infection is
      relevant for evaluating the impact of future HPV immunization initiatives,
      particularly against HR-HPV types other than HPV 16 and 18.

PMID- 23161368
TI  - Effects of a bioassay-derived ivermectin lowest observed effect concentration on
      life-cycle traits of the nematode Caenorhabditis elegans.
AB  - The pharmaceutical ivermectin is used to treat parasitic infections, such as
      those caused by nematodes. While several studies have demonstrated the severe
      effects of ivermectin on non-target organisms, little is known about the drug's
      impact on free-living nematodes. In the present work, a full life-cycle
      experiment was conducted to estimate how an ivermectin lowest observed effect
      concentration derived from a Caenorhabditis elegans bioassay (endpoint
      reproduction) might translate into effects at the population level of this free
      living nematode. The results showed that fecundity decreased to levels similar to
      those determined in the bioassay after a time of corresponding duration (18.6 %
      inhibition compared to the control), but the impact then rather weakened until
      the end of the experiment, at which point the net reproductive rate (R(0)) was
      still, but not significantly, reduced by 12.4 %. Moreover, the average lifespan,
      length of the reproductive period, maximum daily reproduction rate, and intrinsic
      rate of increase (r(m)) were significantly reduced by 30.0, 25.9, 11.2, and 3.5
      %, respectively. The experiment revealed that a 4-day bioassay is protective
      enough for C. elegans with respect to ivermectin's effects on fecundity. However,
      the pronounced effects of a low drug concentration on survival, a highly elastic
      trait, may better account for the observed population-level response, i.e., a
      decrease of r(m), than the effects on fecundity. These results emphasize that
      full life-cycle experiments are valuable for assessment of pollutants, because
      the effects on several life-cycle traits can be simultaneously measured and
      integrated into an ecologically relevant parameter, the population growth rate,
      that reflects a population's response to a specific pollutant.

PMID- 23161369
TI  - Interspecific effects of 4A-DNT (4-amino-2,6-dinitrotoluene) and RDX (1,3,5
      trinitro-1,3,5-triazine) in Japanese quail, Northern bobwhite, and Zebra finch.
AB  - The purpose of this study was to assess the toxicological effects of two munition
      compounds, 4-amino-2,6-dinitrotoluene (4A-DNT) and 1,3,5-trinitro-1,3,5-triazine
      (RDX), on three different bird species: two common toxicological model species
      the Northern Bobwhite (Colinus virginianus) and the Japanese Quail (Coturnix
      japonica), and a representative passerine-the Zebra Finch (Taeniopygia guttata).
      Bobwhite were exposed to 4A-DNT at 0, 8, 15, 30, 60, or 150 mg/kg body weight
      (bw) d by oral gavage for seven days; because the high dose of 4A-DNT was lethal
      to bobwhite, the maximum dose was changed to 100 mg/kg bw d for Japanese quail
      and finches to ensure tissue could be used for future toxicogenomic work. RDX was
      similarly administered at 0, 0.5, 1.5, 3, 6, or 12 mg/kg bw d. Blood was drawn
      prior to euthanasia for blood cellularity and chemistry analyses. Finches were
      clearly least affected by 4A-DNT as evidenced by a lack of observable effects.
      Bobwhite appeared to be the most sensitive species to 4A-DNT as observed through
      changes in blood cellularity and plasma chemistry effects. Bobwhite appeared to
      be more sensitive to RDX than Japanese Quail due to increased effects on measures
      of plasma chemistries. Finches exhibited the greatest sensitivity to RDX through
      increased mortality and seizure activity. This study suggests that sensitivity
      among species is chemical-specific and provides data that could be used to refine
      current avian sensitivity models used in ecological risk assessments.

PMID- 23161372
TI  - Chiral selectors in CE: recent developments and applications.
AB  - This review article provides an overview of the recent advances in
      enantioanalysis by use of electrophoretic techniques. Due to the big number of
      publications in the subject mentioned above, this article is focused on chiral
      method developments and applications published from 2008 until 2011, and it
      demonstrates chiral selectors used in CE. Numerous chiral selectors have been
      used over the years, and these include the cyclic and the linear oligo- and
      polysaccharides, the branched polysaccharides, the polymeric and monomeric
      surfactants, the macrocyclic and other antibiotics, and the crown ethers.
      Different dual-selector systems are also presented in this article, and the
      results are compared with those obtained by use of a single chiral selector.
      Finally, several pharmaceutical and biomedical applications based on chiral
      recognition are summarized.

PMID- 23161373
TI  - Ecological risk assessment in the context of global climate change.
AB  - Changes to sources, stressors, habitats, and geographic ranges; toxicological
      effects; end points; and uncertainty estimation require significant changes in
      the implementation of ecological risk assessment (ERA). Because of the lack of
      analog systems and circumstances in historically studied sites, there is a
      likelihood of type III error. As a first step, the authors propose a decision key
      to aid managers and risk assessors in determining when and to what extent climate
      change should be incorporated. Next, when global climate change is an important
      factor, the authors recommend seven critical changes to ERA. First, develop
      conceptual cause-effect diagrams that consider relevant management decisions as
      well as appropriate spatial and temporal scales to include both direct and
      indirect effects of climate change and the stressor of management interest.
      Second, develop assessment end points that are expressed as ecosystem services.
      Third, evaluate multiple stressors and nonlinear responses-include the chemicals
      and the stressors related to climate change. Fourth, estimate how climate change
      will affect or modify management options as the impacts become manifest. Fifth,
      consider the direction and rate of change relative to management objectives,
      recognizing that both positive and negative outcomes can occur. Sixth, determine
      the major drivers of uncertainty, estimating and bounding stochastic uncertainty
      spatially, temporally, and progressively. Seventh, plan for adaptive management
      to account for changing environmental conditions and consequent changes to
      ecosystem services. Good communication is essential for making risk-related
      information understandable and useful for managers and stakeholders to implement
      a successful risk-assessment and decision-making process.

PMID- 23161371
TI  - Obesity improves myocardial ischaemic tolerance and RISK signalling in insulin
      insensitive rats.
AB  - Obesity with associated metabolic disturbances worsens ischaemic heart disease
      outcomes, and rodent studies confirm that obesity with insulin-resistance impairs
      myocardial resistance to ischemia-reperfusion (I-R) injury. However, the effects
      of obesity per se are unclear, with some evidence for paradoxic cardioprotection
      (particularly in older subjects). We tested the impact of dietary obesity on I-R
      tolerance and reperfusion injury salvage kinase (RISK) signalling in hearts from
      middle-aged (10 months old) insulin-insensitive rats. Hearts from Wistar rats on
      either a 32-week control (CD) or high carbohydrate obesogenic (OB) diet were
      assessed for I-R resistance in vivo (45 minutes left anterior descending artery
      occlusion and 120 minutes reperfusion) and ex vivo (25 minutes ischemia and 60
      minutes reperfusion). Expression and delta-opioid receptor (delta-OR) phospho
      regulation of pro-survival (Akt/PKB, Erk1/2, eNOS) and pro-injury (GSK3beta)
      enzymes were also examined. OB rats were heavier (764 +/- 25 versus 657 +/- 22 g
      for CD; P<0.05), hyperleptinaemic (11.1 +/- 0.7 versus 5.0 +/- 0.7 for CD;
      P<0.01) and comparably insulin-insensitive (HOMA-IR of 63.2 +/- 3.3 versus 63.2
      +/- 1.6 for CD). In vivo infarction was more than halved in OB (20 +/- 3%) versus
      CD rats (45 +/- 6% P<0.05), as was post-ischaemic lactate dehydrogenase efflux
      (0.4 +/- 0.3 mU/ml versus 5.6 +/- 0.5 mU/ml; P<0.02) and ex vivo contractile
      dysfunction (62 +/- 2% versus 44 +/- 6% recovery of ventricular force; P<0.05).
      OB hearts exhibited up to 60% higher Akt expression, with increased
      phosphorylation of eNOS (+100%), GSK3beta (+45%) and Erk1/2 (+15%). Pre-ischaemic
      delta-OR agonism with BW373U86 improved recoveries in CD hearts in association
      with phosphorylation of Akt (+40%), eNOS (+75%) and GSK3beta (+30%), yet failed
      to further enhance RISK-NOS activation or I-R outcomes in OB hearts. In summary,
      dietary obesity in the context of age-related insulin-insensitivity paradoxically
      improves myocardial I-R tolerance, in association with moderate hyperleptinaemic
      and enhanced RISK expression and phospho-regulation. However, OB hearts are
      resistant to further RISK modulation and cardioprotection via acute delta-OR
      agonism.

PMID- 23161370
TI  - Therapeutic potential of growth factors in pulmonary emphysematous condition.
AB  - Pulmonary emphysema is a major manifestation of chronic obstructive pulmonary
      disease (COPD), which is characterized by progressive destruction of alveolar
      parenchyma with persistent inflammation of the small airways. Such destruction in
      the distal respiratory tract is irreversible and irreparable. All-trans-retinoic
      acid was suggested as a novel therapy for regeneration of lost alveoli in
      emphysema. However, profound discrepancies were evident between studies. At
      present, no effective therapeutic options are available that allow for the
      regeneration of lost alveoli in emphysematous human lungs. Recently, some reports
      on rodent's models have suggested the beneficial effects of various growth
      factors toward alveolar maintenance and repair processes.

PMID- 23161374
TI  - Does using comprehensive preoperative bowel preparation offer any advantage for
      urinary diversion using ileum? A meta-analysis.
AB  - PURPOSE: The aim of this study was to compare the efficacy of comprehensive bowel
      preparation to that of limited bowel preparation in prevention of postoperative
      complications in elective urinary diversion surgery by using ileum. METHODS:
      Literature search of PubMed, EMBASE and the Cochrane Library was done to identify
      randomized controlled trials (RCTs) and cohort studies involving comparison of
      postoperative complications after comprehensive bowel preparation and limited
      bowel preparation. A meta-analysis was carried out to distinguish overall
      differences between the two groups. RESULTS: Our literature search yielded two
      randomized controlled trials and two cohort studies, involving a total of 346
      patients, which met our inclusion criteria. There was no significant difference
      between the comprehensive bowel preparation and limited bowel preparation in
      wound infection [relative risk (RR) 95 % confidence interval (CI), 1.05(0.46
      2.40); P = 0.86], mortality [RR 95 % CI, 1.06 (0.32-3.55); P = 0.76], ileus [RR
      95 % CI, 0.86 (0.37, 2.00); P = 0.40], sepsis [RR 95 % CI, 0.71 (0.20, 2.52); P =
      0.78], anastomotic leakage [RR 95 % CI, 0.81 (0.15, 4.21); P = 0.83], wound
      dehiscence [RR 95 % CI, 0.92 (0.40, 2.13); P = 0.67], peritonitis [RR 95 % CI,
      0.64 (0.08, 5.10); P = 0.63] or fistula [RR 95 % CI, 0.71 (0.18,2.75); P = 0.63].
      CONCLUSIONS: The limited evidence available demonstrated that the use of
      comprehensive bowel preparation for urinary diversion surgery using ileum does
      not offer any significant advantage over limited bowel preparation. Future work
      should target more high-quality RCTs to confirm this.

PMID- 23161375
TI  - Neutrophil gelatinase-associated lipocalin is a sensitive biomarker for the early
      diagnosis of acute rejection after living-donor kidney transplantation.
AB  - BACKGROUND: Early diagnosis of kidney allograft dysfunction is crucial for the
      management and long-term survival of transplanted kidneys. We investigated
      whether neutrophil gelatinase-associated lipocalin (NGAL), interleukin 18 (IL
      18), and liver-type fatty acid-binding protein (L-FABP) are capable of being used
      as novel biomarkers of acute kidney allograft dysfunction. METHODS: We measured
      serum and urine NGAL, urine IL-18, and urine L-FABP levels on the first 3 days
      after transplantation. To assess the diagnostic sensitivity of these biomarkers,
      a receiver-operating characteristic curve (ROC) was plotted, and the area under
      the curve (AUC) was calculated to quantify the accuracy of the parameter.
      Sections from paraffin-embedded biopsy specimens were examined by
      immunohistochemistry for NGAL expression. RESULTS: Twelve cases were clinically
      diagnosed as acute rejection (AR) by renal biopsy. Urine NGAL was the most
      sensitive of these markers for detection of acute kidney allograft dysfunction.
      The cutoff value of urine NGAL was 66.0 ng/ml, with an AUC of 0.79 (95 % CI 0.68
      0.88). Sensitivity of serum NGAL was about the same as urine NGAL with an AUC of
      0.75 (0.64-0.85). IL-18 and L-FABP were 0.584 (95 % CI 0.433-0.725) and 0.612 (95
      % CI 0.460-0.749), respectively. NGAL was more useful than other biomarkers to
      detect AR of kidney allograft dysfunction. NGAL staining intensity was
      significantly increased in the proximal tubules of the transplants with AR than
      in transplants that were not acutely rejected. CONCLUSION: Urine NGAL level was
      found to be the most sensitive biomarker of acute kidney allograft dysfunction
      after living-donor kidney transplantation.

PMID- 23161376
TI  - Views of Japanese patients on the advantages and disadvantages of hemodialysis
      and peritoneal dialysis.
AB  - PURPOSE: The preference for dialysis modalities is not well understood in Japan.
      This study explored the subjective views of Japanese patients undergoing dialysis
      regarding their treatments. METHODS: The participants were receiving in-center
      hemodialysis (CHD) or continuous ambulatory peritoneal dialysis (CAPD). In Study
      1, 34 participants (17 CHD and 17 CAPD) were interviewed about the advantages and
      disadvantages of dialysis modalities. In Study 2, 454 dialysis patients (437 CHD
      and 17 CAPD) rated the advantages and disadvantages of CHD and CAPD in a cross
      sectional survey. RESULTS: Interviews showed that professional care and dialysis
      free days were considered as advantages of CHD, while independence, less hospital
      visits, and flexibility were considered as advantages of CAPD. Disadvantages of
      CHD included restriction of food and fluids and unpleasant symptoms after each
      dialysis session. Catheter care was an additional disadvantage of CAPD. Survey
      showed that the highly ranked advantages were professional care in CHD and less
      frequent hospital visits in CAPD, while the highly ranked disadvantages were
      concerns about emergency and time restrictions in CHD, and catheter care and
      difficulty in soaking in a bath in CAPD. The total scores of advantages and
      disadvantages showed that CHD patients subjectively rated their own modality
      better CHD over CAPD, while CAPD patients had the opposite opinion. CONCLUSIONS:
      The results of this study indicate that the factors affecting the decision-making
      process of Japanese patients are unique to Japanese culture, namely considering
      the trouble caused to the people around patients (e.g., families, spouses, and/or
      caregivers).

PMID- 23161377
TI  - Determinants of anxiety in patients with advanced somatic disease: differences
      and similarities between patients undergoing renal replacement therapies and
      patients suffering from cancer.
AB  - OBJECTIVE: Anxiety is the most frequent emotional reaction to the chronic somatic
      disease. However, little is known about anxiety and coping strategies in patients
      with end-stage renal disease (ESRD) undergoing renal replacement therapies
      (RRTs). The purpose of the study was to assess the intensity and determinants of
      anxiety in patients treated with different RRTs in comparison with end-stage
      breast cancer patients and healthy controls. METHODS: The study involved (1) ESRD
      patients undergoing different RRTs: 32 renal transplant recipients, 31
      maintenance haemodialysis and 21 chronic peritoneal dialysis patients, (2) women
      with end-stage breast cancer (n = 25) and (3) healthy persons (n = 55). We used
      State-Trait Anxiety Inventory, Scale of Personal Religiousness, Mental Adjustment
      to Cancer Scale, Rotterdam Symptom Checklist with reference to medical history.
      The data thus obtained were analysed using the analysis of variance, the Tukey's
      HSD post hoc test and Spearman's rank correlation coefficient. RESULTS: Both ESRD
      and breast cancer patients revealed higher level of anxiety state and trait than
      healthy controls; however, there was no statistically significant difference
      found between both findings. There was a tendency towards higher levels of
      anxiety state in breast cancer patients when compared to ESRD patients undergoing
      the RRT treatment and for both groups non-constructive coping strategies
      correlated with the levels of anxiety state. With ESRD patients undergoing RRTs,
      the intensity of anxiety state did not depend on the mode of treatment but on the
      correlation between the levels of anxiety and the general quality of their life,
      psychological condition and social activity. CONCLUSION: In patients with
      advanced somatic disease (ESRD and end-stage breast cancer), non-constructive
      strategies of coping with the disease require further evaluation and possibly
      psychological support.

PMID- 23161378
TI  - Factors that impact the outcome of endoscopic correction of vesicoureteral
      reflux: a multivariate analysis.
AB  - PURPOSE: To identify independent factors that may predict vesicoureteral reflux
      (VUR) resolution after endoscopic treatment using dextranomer/hyaluronic acid
      copolymer (Deflux) in children free of anatomical anomalies. MATERIALS AND
      METHODS: A retrospective study was conducted in our pediatric referral center
      from 1998 to 2011 on children with primary VUR who underwent endoscopic injection
      of Deflux with or without concomitant autologous blood injection (called HABIT or
      HIT, respectively). Children with secondary VUR or incomplete records were
      excluded from the study. Potential factors were divided into three categories
      including preoperative, intraoperative and postoperative. Success was defined as
      no sign of VUR on postoperative voiding cystourethrogram. Univariate and
      multivariate logistic regression models were constructed to identify independent
      factors that may predict success. Odds ratio (OR) and 95 % confidence interval
      (95 % CI) for prediction of success were estimated for each factor. RESULTS: From
      485 children received Deflux injection, a total of 372 with a mean age of 3.10
      years (ranged from 6 months to 12 years) were included in the study and
      endoscopic management was successful in 322 (86.6 %) of them. Of the patients,
      185 (49.7 %) underwent HIT and 187 (50.3 %) underwent HABIT technique. On
      univariate analysis, VUR grade from preoperative category (OR = 4.79, 95 % CI =
      2.22-10.30, p = 0.000), operation technique (OR = 0.33, 95 % CI = 0.17-0.64, p =
      0.001) and presence of mound on postoperative sonography (OR = 0.06, 95 % CI =
      0.02-0.16, p = 0.000) were associated with success. On multivariate analysis,
      preoperative VUR grade (OR = 4.85, 95 % CI = 2.49-8.96, p = 0.000) and
      identification of mound on postoperative sonography (OR = 0.07, 95 % CI = 0.01
      0.18, p = 0.000) remained as independent success predictors. CONCLUSION: Based on
      this study, successful VUR correction after the endoscopic injection of Deflux
      can be predicted with respect to preoperative VUR grade and presence of mound
      after operation.

PMID- 23161380
TI  - Two-phase electro-hydrodynamic flow modeling by a conservative level set model.
AB  - The principles of electro-hydrodynamic (EHD) flow have been known for more than a
      century and have been adopted for various industrial applications, for example,
      fluid mixing and demixing. Analytical solutions of such EHD flow only exist in a
      limited number of scenarios, for example, predicting a small deformation of a
      single droplet in a uniform electric field. Numerical modeling of such phenomena
      can provide significant insights about EHDs multiphase flows. During the last
      decade, many numerical results have been reported to provide novel and useful
      tools of studying the multiphase EHD flow. Based on a conservative level set
      method, the proposed model is able to simulate large deformations of a droplet by
      a steady electric field, which is beyond the region of theoretic prediction. The
      model is validated for both leaky dielectrics and perfect dielectrics, and is
      found to be in excellent agreement with existing analytical solutions and
      numerical studies in the literature. Furthermore, simulations of the deformation
      of a water droplet in decyl alcohol in a steady electric field match better with
      published experimental data than the theoretical prediction for large
      deformations. Therefore the proposed model can serve as a practical and accurate
      tool for simulating two-phase EHD flow.

PMID- 23161379
TI  - Progress toward the application of molecular force spectroscopy to DNA
      sequencing.
AB  - Many recent advances in DNA sequencing have taken advantage of single-molecule
      techniques using fluorescently labeled oligonucleotides as the principal mode of
      detection. However, in spite of the successes of fluorescent-based sequencers,
      avoidance of labeled nucleotides could substantially reduce the costs of
      sequencing. This article discusses the development of an alternative sequencing
      method in which unlabeled DNA can be manipulated directly on a massively parallel
      scale using single-molecule force spectroscopy. We combine a wide-field optical
      detection technique (evanescent field excitation) with one of two methods of
      applying force in parallel, magnetic or dielectrophoretic tweezers, to attain
      near single-base sensitivity in the double-stranded character of DNA. This
      article will discuss the developments of such a single-molecule force
      spectroscopy technique as a potential technology for genome sequencing.

PMID- 23161381
TI  - No evidence of the genotoxic potential of gold, silver, zinc oxide and titanium
      dioxide nanoparticles in the SOS chromotest.
AB  - Gold nanoparticles (Au NPs), silver nanoparticles (Ag NPs), zinc oxide
      nanoparticles (ZnO NPs) and titanium dioxide nanoparticles (TiO2 NPs) are widely
      used in cosmetic products such as preservatives, colorants and sunscreens. This
      study investigated the genotoxicity of Au NPs, Ag NPs, ZnO NPs and TiO2 NPs using
      the SOS chromotest with Escherichia coli PQ37. The maximum exposure
      concentrations for each nanoparticle were 3.23 mg l(-1) for Au NPs, 32.3 mg l(-1)
      for Ag NPs and 100 mg l(-1) for ZnO NPs and TiO2 NPs. Additionally, in order to
      compare the genotoxicity of nanoparticles and corresponding dissolved ions, the
      ions were assessed in the same way as nanoparticles. The genotoxicity of the
      titanium ion was not assessed because of the extremely low solubility of TiO2
      NPs. Au NPs, Ag NPs, ZnO NPs, TiO2 NPs and ions of Au, Ag and Zn, in a range of
      tested concentrations, exerted no effects in the SOS chromotest, evidenced by
      maximum IF (IFmax) values of below 1.5 for all chemicals. Owing to the results,
      nanosized Au NPs, Ag NPs, ZnO NPs, TiO2 NPs and ions of Au, Ag and Zn are
      classified as non-genotoxic on the basis of the SOS chromotest used in this
      study. To the best of our knowledge, this is the first study to evaluate the
      genotoxicity of Au NPs, Ag NPs, ZnO NPs and TiO2 NPs using the SOS chromotest.

PMID- 23161383
TI  - Free hemiback flap with surgical delay for reconstruction of extensive soft
      tissue defect: a case report.
AB  - A delay procedure allows for reliable tissue transfer in random pattern flaps and
      axial pattern flaps. However, delay procedures have not been studied in free
      flaps. In this report, we present a case involving the use of a free extended
      latissimus dorsi musculocutaneous flap (hemiback flap) that included half of the
      total back skin and was based on thoracodorsal vessels for reconstruction of an
      extensive soft tissue defect of the flank and waist. The flap was tailored in
      combination with a delay procedure. Intraoperative indocyanine green fluorescence
      angiography indicated profuse perfusion except for the most inferomedial part of
      the flap, which was discarded. The flap survived. A free hemiback flap may offer
      a valuable option for reconstruction of extensive soft tissue defects. To our
      knowledge, this is the first report to demonstrate a free flap made in
      combination with a delay procedure.

PMID- 23161384
TI  - A simple sample pretreatment device with supported liquid membrane for direct
      injection of untreated body fluids and in-line coupling to a commercial CE
      instrument.
AB  - A simple sample pretreatment device was developed employing extractions across
      supported liquid membranes (SLMs) and in-line coupling to a commercial CE
      instrument. The device consisted of two polypropylene conical units interspaced
      with a polypropylene planar SLM, which were impregnated with 1-ethyl-2
      nitrobenzene. The two units and the SLM were pressed against each other, donor
      unit was filled with 40 MUL of an untreated body fluid and acceptor unit with 40
      MUL of DI water. The device was then placed into conventional CE vial fitted with
      a soft spring, which was depressed during injection into CE capillary and ensured
      that the SLM was not ruptured. Position of separation capillary injection end and
      high-voltage electrode in the CE instrument was optimized in order to ensure
      efficient injection of pretreated body fluids. The device can be easily
      assembled/disassembled and SLMs can be replaced after each extraction thus
      minimizing sample carry-over, avoiding tedious SLM regeneration, and reducing
      total pretreatment time and costs. The pretreatment device was examined by direct
      injection of human urine and serum spiked with nortriptyline, haloperidol, and
      loperamide. The basic drugs were diffusionaly transported across the SLM within
      10 min and were injected into the separation capillary directly from the SLM
      surface in the acceptor unit, whereas matrix components were retained by the SLM.
      The in-line SLM-CE method showed good repeatability of peak areas (3.8-11.0%) and
      migration times (below 1.4%), linear relationship (r(2)  = 0.990-0.999), and low
      LODs (12-100 MUg/L).

PMID- 23161385
TI  - The current status of robotic oncologic surgery.
AB  - The use of robotic assistance facilitates minimally invasive surgery and has been
      widely adopted across multiple specialties. This article reviews the published
      literature on use of this technology for treatment of oncologic conditions.
      PubMed searches were performed for articles published between 2000 and 2012 using
      the keywords "robotic" or "robotic surgery" in conjunction with "oncology" or
      "cancer." Although the most common use for robotics was to treat urologic
      oncologic conditions, it has also been widely adopted for gynecologic, general,
      thoracic, and head and neck surgeries. For several procedures, there is evidence
      that robotics offers short-term benefits such as shorter lengths of stay and
      lower intraoperative blood loss, with safety profiles and oncologic outcomes
      comparable to open or conventional laparoscopic approaches. However, long-term
      oncologic outcomes are generally lacking, and robotic surgeries are more costly
      than open or laparoscopic surgeries. Robotic technology is widely used in
      oncologic surgery with demonstrated short-term advantages. However, whether the
      benefits of robotics justify the higher costs warrant large comparative
      effectiveness studies with long-term outcomes.

PMID- 23161382
TI  - Histone methylation in the nervous system: functions and dysfunctions.
AB  - Chromatin remodeling is a key epigenetic process controlling the regulation of
      gene transcription. Local changes of chromatin architecture can be achieved by
      post-translational modifications of histones such as methylation, acetylation,
      phosphorylation, ubiquitination, sumoylation, and ADP-ribosylation. These changes
      are dynamic and allow for rapid repression or de-repression of specific target
      genes. Chromatin remodeling enzymes are largely involved in the control of
      cellular differentiation, and loss or gain of function is often correlated with
      pathological events. For these reasons, research on chromatin remodeling enzymes
      is currently very active and rapidly expanding, these enzymes representing very
      promising targets for the design of novel therapeutics in different areas of
      medicine including oncology and neurology. In this review, we focus on histone
      methylation in the nervous system. We provide an overview on mammalian histone
      methyltransferases and demethylases and their mechanisms of action, and we
      discuss their roles in the development of the nervous system and their
      involvement in neurodevelopmental, neurodegenerative, and behavioral disorders.

PMID- 23161386
TI  - Establishment and characterization of two fetal fibroblast cell lines from the
      yak.
AB  - The objective of this work was to not only establish two fetal fibroblast cell
      lines from yak lung and ear tissue using a primary explant technique and cell
      cryogenic preservation technology but also check for their quality and biological
      characteristics. The cells showed typical morphologic characteristics of fibrous
      and long spindle appearance. Outgrowth of fibroblast-like cells from the lung and
      ear explants was around 2 and 3 d, and reaching 90% confluence level was in the
      ninth day and the thirteenth day, respectively. Biological analysis showed that
      the average viability of the lung fibroblast cells (ear fibroblast cells) was
      97.5% (95.0%) before freezing and 91.0% (89.5%) after thawing. Analysis of the
      growth of the fifth passage culture revealed an "S"-shaped growth curve with the
      population doubling times of 30 h for lung fibroblast cell line and 35 h for ear
      fibroblast cell line. Karyotyping indicated the chromosome number of yak was 2n =
      60, comprising 29 pairs of autosomes and one pair of sex chromosomes (XY). All
      somatic chromosomes were telocentric autosomes except that the two sex
      chromosomes were submetacentric. Assays for bacteria, fungi, and mycoplasmas were
      negative. Immunocytochemical staining showed that the cells were positive for the
      expression of vimentin and negative for the expression of cytokeratin. In
      conclusion, two yak fetal fibroblast cell lines (YFLF and YFEF) from lung and ear
      explants are successfully established in culture. It will not only preserve the
      genetic resources of yaks at the cellular level but also provide valuable
      materials for somatic cell cloning and transgenic research.

PMID- 23161388
TI  - Early death in patients diagnosed with non-Hodgkin's lymphoma.
AB  - This study sought to identify risk factors for early death in non-Hodgkin's
      lymphoma (NHL). The databases of a tertiary medical center were reviewed for
      adult patients diagnosed with NHL since 1985 who died within 4 months of
      diagnosis. Comprehensive background, disease-related data, and treatment-related
      data were collected and analyzed by descriptive statistics. Ninety-two patients
      (7 % of the patient registry) met the inclusion criteria: 40 men and 52 women of
      mean age 74 years. Most (86 %) had B cell NHL; the most frequent pathologic
      classification was diffuse large B cell lymphoma (75 %). Rates of other disease
      related factors were as follows: aggressive disease, 90 %; stage IV, 73 %; bulky
      disease, 66 %; extranodal involvement, 86 % (usually >1 site); performance score
      2-4, 76 %; international prognostic index 3-5, 89 %; and B symptoms, 84 %. Mean
      Ki-67 proliferation index was 71 %. Additionally, 80 % of patients had a high
      lactose dehydrogenase level, 89 % a high beta-2 microglobulin level, and 47 %
      serosal (mainly pleural) effusion. A history of other cancer or organ
      transplantation was documented in 24 %. Chemotherapy was administered to 59 %,
      mostly CHOP. In conclusion, early death occurs in at least 7 % of patients with
      newly diagnosed NHL. This patient group is characterized by older age, aggressive
      lymphoma, poor performance status, advanced-stage disease, extranodal disease, B
      symptoms, bulky disease, elevated lactate dehydrogenase and beta-2 microglobulin
      levels, and serosal effusion. These early death resulted from sepsis, severe
      underlying disease, disease progression, or gastrointestinal perforation. The
      selection of appropriate treatment modalities for these patients with poor
      prognostic features is a real challenge. They should undergo comprehensive
      geriatric assessment and receive individualized tailored treatments with protocol
      adjustment to their condition, strict clinical surveillance, best supportive
      care, and maybe, as recently suggested, a prephase treatment.

PMID- 23161387
TI  - Rapid and highly specific screening for NPM1 mutations in acute myeloid leukemia.
AB  - NPM1 mutations, the most frequent molecular alterations in acute myeloid leukemia
      (AML), have become important for risk stratification and treatment decisions for
      patients with normal karyotype AML. Rapid screening for NPM1 mutations should be
      available shortly after diagnosis. Several methods for detecting NPM1 mutations
      have been described, most of which are technically challenging and require
      additional laboratory equipment. We developed and validated an assay that allows
      specific, rapid, and simple screening for NPM1 mutations. FAST PCR spanning exons
      8 to 12 of the NPM1 gene was performed on 284 diagnostic AML samples. PCR
      products were visualized on a 2 % agarose E-gel and verified by direct
      sequencing. The FAST PCR screening method showed a specificity and sensitivity of
      100 %, i.e., all mutated cases were detected, and none of negative cases carried
      mutations. The limit of detection was at 5-10 % of mutant alleles. We conclude
      that the FAST PCR assay is a highly specific, rapid (less than 2 h), and
      sensitive screening method for the detection of NPM1 mutations. Moreover, this
      method is inexpensive and can easily be integrated in the routine molecular
      diagnostic work-up of established risk factors in AML using standard laboratory
      equipment.

PMID- 23161389
TI  - Functional analysis of a novel KLF1 gene promoter variation associated with
      hereditary persistence of fetal hemoglobin.
AB  - Hereditary persistence of fetal hemoglobin (HPFH) is a rare hereditary condition
      resulting in elevated levels of fetal hemoglobin (HbF) in adults. Typical HPFH is
      associated with promoter mutations or large deletions affecting the human fetal
      globin (HBG1 and HBG2) genes, while genetic defects in other genes involved in
      human erythropoiesis, e.g. KLF1, also result in atypical HPFH. Here, we report
      the first KLF1 gene promoter mutation (KLF1:g.-148G > A) that is associated with
      increased HbF level. This mutation was shown to result in drastically reduced CAT
      reporter gene expression in K562 cells, compared to the wild-type sequence (p =
      0.009) and also in reduced KLF1 gene expression in vivo. Furthermore, consistent
      with in silico analysis, electrophoretic mobility shift analysis showed that the
      KLF1:g.-148G > A mutation resides in a Sp1 binding site and further that this
      mutation leads to the ablation of Sp1 binding in vitro. These data suggest that
      the KLF1:g-148G > A mutation could play a role in increasing HbF levels in adults
      and further underlines the role of KLF1 as one of the key transcription factors
      involved in human fetal globin gene switching.

PMID- 23161390
TI  - Differential plasma proteome profiles of mild versus severe beta-thalassemia/Hb
      E.
AB  - The severity of thalassemia is currently classified based on clinical
      manifestations and multiple tests. In the present study, we performed a plasma
      proteome analysis to identify differentially expressed proteins compared between
      normal subjects and patients with mild and severe forms of beta
      thalassemia/hemoglobin E (Hb E). Plasma samples were collected from patients with
      mild (n = 8) and severe (n = 12) forms as well as healthy normal individuals (n =
      12). Clinical chemistry revealed that several parameters, i.e., hematological
      indices, oxidative stress markers, antioxidant enzymes, and erythropoietic
      activity, had significant differences among these three groups. After removal of
      seven major abundant proteins, the plasma proteome profiles were compared using
      two-dimensional gel electrophoresis. Spot matching, quantitative intensity
      analysis, and statistics revealed differential levels of 32 and 9 proteins when
      comparing normal vs. patients and mild vs. severe forms, respectively. These
      proteins were successfully identified by quadrupole time-of-flight mass
      spectrometry and/or tandem mass spectrometry. The decreased level of ADP
      ribosylation factor guanine nucleotide-exchange factor 2 in beta-thalassemia/Hb E
      patients compared to healthy individuals and the decreased level of endothelin
      converting enzyme 2 in severe form compared to the mild form of the disease were
      validated by Western blot analysis. Our data provide a number of proteins that
      may lead to better understanding of the pathophysiology of thalassemia or for
      novel biomarkers which can be used to simply differentiate mild and severe forms
      of beta-thalassemia/Hb E without any need for multiple tests.

PMID- 23161391
TI  - Escherichia coli and Klebsiella pneumoniae bacteremia in patients with
      neutropenic fever: factors associated with extended-spectrum beta-lactamase
      production and its impact on outcome.
AB  - Escherichia coli and Klebsiella pneumoniae are main pathogens in neutropenic
      fever even if the proportion of Gram-positive cocci is increasing. Extended
      spectrum beta-lactamases (ESBL)-producing organisms are an emerging problem in
      nosocomial infection. Nevertheless, until now, information about risk factors for
      the acquisition and clinical outcomes of bacteremia due to ESBL-producing
      organisms is limited in neutropenic patients. From medical records collected
      between January 2007 and December 2008, we identified a total of 101 consecutive
      patients who developed bacteremia due to E. coli (n = 87) or K. pneumoniae (n =
      14). Twenty-six (26 %) cases of bacteremia were caused by ESBL-producing
      organisms. A hospital stay of >2 weeks during the 3 months preceding bacteremia
      [adjusted odds ratio (OR), 5.887; 95 % confidence interval (CI), 1.572-22.041]
      and the use of broad-spectrum cephalosporins in the 4 weeks prior to bacteremia
      (adjusted OR, 6.186; 95 % CI, 1.616-23.683) were significantly related to the
      acquisition of ESBL. Twenty-four (92 %) of the ESBL-producing organisms were
      susceptible to either piperacillin-tazobactam or amikacin. Aminoglycosides
      (amikacin or isepamicin) were the main appropriate antimicrobial agents used
      against the ESBL-producing isolates during the initial empirical treatment
      (16/22, 73 %). However, the 30-day mortality rates for ESBL bacteremia and non
      ESBL bacteremia were not significantly different (15 vs 5 %; p = 0.199). As
      alternatives to carbapenem, piperacillin-tazobactam plus amikacin or isepamicin
      combinations may be effective empirical therapeutic options for patients with
      neutropenic fever who are at high risk of developing bacteremia with ESBL
      producing pathogens.

PMID- 23161392
TI  - Do nonnative language speakers chew the fat and spill the beans with different
      brain hemispheres? Investigating idiom decomposability with the divided visual
      field paradigm.
AB  - The purpose of this study was to explore possible cerebral asymmetries in the
      processing of decomposable and nondecomposable idioms by fluent nonnative
      speakers of English. In the study, native language (Polish) and foreign language
      (English) decomposable and nondecomposable idioms were embedded in ambiguous
      (neutral) and unambiguous (biasing figurative meaning) context and presented
      centrally, followed by laterally presented target words related to the figurative
      meaning of the idiom or literal meaning of the last word of the idiom. The target
      appeared either immediately at sentence offset (Experiment 1), or 400 ms
      (Experiment 2) after sentence offset. Results are inconsistent with the Idiom
      Decomposition Hypothesis (Gibbs et al. in Mem Cogn 17:58-68, 1989a; J Mem Lang
      28:576-593, 1989b) and only partially consistent with the idea of the
      differential cerebral involvement in processing (non)decomposable idioms [the
      Fine/Coarse Coding Theory, Beeman (Right hemisphere language comprehension:
      perspectives from cognitive neuroscience, Lawrence Erlbaum Associates, Mahwah,
      NJ, 1998)]. A number of factors, rather than compositionality per se, emerge as
      crucial in determining idiom processing, such as language status (native vs.
      nonnative), salience, or context.

PMID- 23161393
TI  - Hindpaw withdrawal from a painful thermal stimulus after sciatic nerve
      compression and decompression in the diabetic rat.
AB  - INTRODUCTION: Although the effect of chronic compression and surgical
      decompression of the diabetic rat sciatic nerve has been evaluated by walking
      track analysis, the measurement of sensory function by response to thermal
      nociceptive stimulation has not been investigated. METHODS: Fifteen male Wistar
      rats with streptozotocin-induced diabetes underwent sciatic nerve compression
      through a 10-mm silicone band. Five rats had histology done 60 days after
      confirming chronic nerve compression. Pain threshold was measured using hindlimb
      withdrawal times (HLWT) from a heat stimulus. After 60 days of compression, the
      silicone tube was removed. Five nondiabetic, nonbanded rats were used as
      controls. RESULTS: Control mean HLWT was 9.7 +/- 1.5 sec. In the diabetes group
      (60 days of compression), mean HLWT was 23.6 +/- 2.4 sec. (p < 0.001). Thirty
      days after removal of the silicone, mean HLWT to painful stimuli was 14.9 +/- 1.5
      sec. (p < 0.001). CONCLUSION: Chronic compression of the diabetic rat sciatic
      nerve increases (worsens) the threshold to heat (pain) perception. Decompression
      reverses this effect (improves nociception).

PMID- 23161394
TI  - Tired eyes from microsurgery--it's blinking obvious!

PMID- 23161395
TI  - Urinary metabolites after intravenous propofol bolus in neonates.
AB  - In neonates, propofol mainly undergoes hydroxylation to quinol metabolites with
      only limited glucuronidation. The aim of this study is to search for covariates
      of neonatal propofol biotransformation based on 24 h urine collections. In
      neonates receiving an intravenous propofol bolus for short procedural sedation,
      urine was collected during 24 h. Urinary propofol metabolites [propofol
      glucuronide (PG), 1- and 4-quinol glucuronide (QG)] were determined using high
      performance liquid chromatography after a dual-step solid phase extraction
      combined with ultraviolet and fluorescence detection. Propofol metabolites, their
      contribution to total metabolite elimination and propofol glucuronide/quinol
      glucuronide (PG/QG) ratio were determined. The impact of continuous
      [postmenstrual age (PMA), postnatal age (PNA), body weight, propofol dose,
      creatinaemia] and dichotomous variables [PNA <= 7 days (yes/no), PNA >= 10 days
      (yes/no), hyperbilirubinaemia (yes/no), cardiopathy (yes/no)] on PG/QG ratio and
      on patients with low (<=10 %) vs. high (>10 %) urinary PG recovery were examined.
      Thirty-two neonates were included. Median total propofol metabolite recovery was
      40.95 (2.01-129.81) % with PG/QG ratio 0.44 (0.01-5.93). PNA (dichotomous 7 days
      as well as 10 days) was a significant covariate of PG/QG ratio. Late PNA more
      frequently resulted in high urinary PG fraction. Significance was more pronounced
      with PNA 10 days as cut-off point for early neonatal life compared to 7 days. Age
      10 days is pivotal in early life propofol metabolism. This confirms earlier
      documented propofol clearance studies. This is the first report of the modified
      quantification assay used to determine urinary propofol metabolites in neonates.

PMID- 23161397
TI  - Effect of ketoprofen and indomethacin on methotrexate pharmacokinetics in mice
      plasma and tumor tissues.
AB  - Methotrexate (MTX) has been used in combination with nonsteroidal anti
      inflammatory drugs in the treatment of inflammatory diseases as well as
      malignancies. Severe adverse effects with this combination may occur, usually
      resulting from inhibition of renal transporters. Solid Ehrlich carcinoma was
      experimentally induced by implantation of Ehrlich ascites Carcinoma cells
      subcutaneously into the thigh of mice, and after 30 days, mice were divided into
      three groups: Group I that served as control group received MTX (50 mg/kg, i.p.);
      Group II received ketoprofen (100 mg/kg, i.p.) and then after half an hour
      received MTX (50 mg/kg, i.p.); Group III received indomethacin (10 mg/kg, i.p.)
      and then after half an hour received MTX (50 mg/kg, i.p.). Plasma and tissue
      samples were collected at different time points and then MTX concentrations were
      determined by HPLC. The injection of ketoprofen or indomethacin before MTX
      injection resulted in significant increase in the AUC and CPmax of MTX (p < 0.05)
      and significant decrease in CL/F and Vd/F of MTX (p < 0.05) in mice plasma. The
      effects were more significant after injection of indomethacin than in case of
      ketoprofen. The study showed that administration of ketoprofen or indomethacin
      prior to MTX caused significant decrease in MTX elimination and significant
      increase in MTX extent of absorption which may lead to severe adverse effects if
      coadministered in human.

PMID- 23161398
TI  - Genetic and antigenic evolution profiles of G1 rotaviruses in cordoba, Argentina,
      during a 27-year period (1980-2006).
AB  - Rotavirus G1 strains represent the most common genotype that causes diarrhea in
      humans and has been incorporated into both, monovalent and multivalent, rotavirus
      licensed vaccines. The aim of this study was to determine the evolution profile
      of G1 rotaviruses in Cordoba, Argentina, over a 27-year period (1980-2006).
      Intragenotype diversity, represented by lineages within rotavirus circulating
      strains, was observed. Phylogenetic analysis of the VP7-gene of G1 rotavirus
      clinical strains showed the circulation of G1 lineage IV and V strains in the
      1980s, and co-circulation of lineage I and II strains in the 1990s and 2000-2006.
      The distribution of G1 in lineages could be linked to multiple nucleotide
      substitutions distributed across lineages that did not correlate with the
      emergence of G1 antigenic variants. Moreover, temporal lineage distribution was
      not linked to significant changes in G1 prevalence. Therefore, the continuous and
      dominant circulation of G1 over time could not be related to the emergence of
      antigenic variants in the community. Continuous rotavirus surveillance is
      necessary to understand rotavirus evolution and to measure how genetic and
      antigenic changes might affect the effectiveness of vaccines in the future.

PMID- 23161396
TI  - Isoflavones: estrogenic activity, biological effect and bioavailability.
AB  - Isoflavones are phytoestrogens with potent estrogenic activity; genistein,
      daidzein and glycitein are the most active isoflavones found in soy beans.
      Phytoestrogens have similarity in structure with the human female hormone 17-beta
      estradiol, which can bind to both alpha and beta estrogen receptors, and mimic
      the action of estrogens on target organs, thereby exerting many health benefits
      when used in some hormone-dependent diseases. Numerous clinical studies claim
      benefits of genistein and daidzein in chemoprevention of breast and prostate
      cancer, cardiovascular disease and osteoporosis as well as in relieving
      postmenopausal symptoms. The ability of isoflavones to prevent cancer and other
      chronic diseases largely depends on pharmacokinetic properties of these
      compounds, in particular absorption and distribution to the target tissue. The
      chemical form in which isoflavones occur is important because it influences their
      bioavailability and, therefore, their biological activity. Glucose-conjugated
      isoflavones are highly polar, water-soluble compounds. They are hardly absorbed
      by the intestinal epithelium and have weaker biological activities than the
      corresponding aglycone. Different microbial families of colon can transform
      glycosylated isoflavones into aglycones. Clinical studies show important
      differences between the aglycone and conjugated forms of genistein and daidzein.
      The evaluation of isoflavone metabolism and bioavailability is crucial to
      understanding their biological effects. Lipid-based formulations such as drug
      incorporation into oils, emulsions and self-microemulsifying formulations have
      been introduced to increase bioavailability. Complexation with cyclodextrin also
      represent a valid method to improve the physicochemical characteristics of these
      substances in order to be absorbed and distributed to target tissues. We review
      and discuss pharmacokinetic issues that critically influence the biological
      activity of isoflavones.

PMID- 23161399
TI  - Natural flexible dermal armor.
AB  - Fish, reptiles, and mammals can possess flexible dermal armor for protection.
      Here we seek to find the means by which Nature derives its protection by
      examining the scales from several fish (Atractosteus spatula, Arapaima gigas,
      Polypterus senegalus, Morone saxatilis, Cyprinius carpio), and osteoderms from
      armadillos, alligators, and leatherback turtles. Dermal armor has clearly been
      developed by convergent evolution in these different species. In general, it has
      a hierarchical structure with collagen fibers joining more rigid units (scales or
      osteoderms), thereby increasing flexibility without significantly sacrificing
      strength, in contrast to rigid monolithic mineral composites. These dermal
      structures are also multifunctional, with hydrodynamic drag (in fish), coloration
      for camouflage or intraspecies recognition, temperature and fluid regulation
      being other important functions. The understanding of such flexible dermal armor
      is important as it may provide a basis for new synthetic, yet bioinspired, armor
      materials.

PMID- 23161400
TI  - Neutron relative biological effectiveness for solid cancer incidence in the
      Japanese A-bomb survivors: an analysis considering the degree of independent
      effects from gamma-ray and neutron absorbed doses with hierarchical partitioning.
AB  - It has generally been assumed that the neutron and gamma-ray absorbed doses in
      the data from the life span study (LSS) of the Japanese A-bomb survivors are too
      highly correlated for an independent separation of the all solid cancer risks due
      to neutrons and due to gamma-rays. However, with the release of the most recent
      data for all solid cancer incidence and the increased statistical power over
      previous datasets, it is instructive to consider alternatives to the usual
      approaches. Simple excess relative risk (ERR) models for radiation-induced solid
      cancer incidence fitted to the LSS epidemiological data have been applied with
      neutron and gamma-ray absorbed doses as separate explanatory covariables. A
      simple evaluation of the degree of independent effects from gamma-ray and neutron
      absorbed doses on the all solid cancer risk with the hierarchical partitioning
      (HP) technique is presented here. The degree of multi-collinearity between the
      gamma-ray and neutron absorbed doses has also been considered. The results show
      that, whereas the partial correlation between the neutron and gamma-ray colon
      absorbed doses may be considered to be high at 0.74, this value is just below the
      level beyond which remedial action, such as adding the doses together, is usually
      recommended. The resulting variance inflation factor is 2.2. Applying HP
      indicates that just under half of the drop in deviance resulting from adding the
      gamma-ray and neutron absorbed doses to the baseline risk model comes from the
      joint effects of the neutrons and gamma-rays-leaving a substantial proportion of
      this deviance drop accounted for by individual effects of the neutrons and gamma
      rays. The average ERR/Gy gamma-ray absorbed dose and the ERR/Gy neutron absorbed
      dose that have been obtained here directly for the first time, agree well with
      previous indirect estimates. The average relative biological effectiveness (RBE)
      of neutrons relative to gamma-rays, calculated directly from fit parameters to
      the all solid cancer ERR model with both colon absorbed dose covariables, is 65
      (95 %CI: 11; 170). Therefore, although the 95 % CI is quite wide, reference to
      the colon doses with a neutron weighting of 10 may not be optimal as the basis
      for the determination of all solid cancer risks. Further investigations into the
      neutron RBE are required, ideally based on the LSS data with organ-specific
      neutron and gamma-ray absorbed doses for all organs rather than the RBE weighted
      absorbed doses currently provided. The HP method is also suggested for use in
      other epidemiological cohort analyses that involve correlated explanatory
      covariables.

PMID- 23161402
TI  - Intraneuronal beta-amyloid and its interactions with proteins and subcellular
      organelles.
AB  - Amyloidogenic aggregation and misfolding of proteins are linked to
      neurodegeneration. The mechanism of neurodegeneration in Alzheimer's disease,
      which gives rise to severe neuronal death and memory loss, is not yet fully
      understood. The amyloid hypothesis remains the most accepted theory for the
      pathomechanism of the disease. It was suggested that beta-amyloid accumulation
      may play a key role in initiating the neurodegenerative processes. The recent
      intracellular beta-amyloid (iAbeta) hypothesis emphasizes the primary role of
      iAbeta to initiate the disease by interaction with cytoplasmic proteins and cell
      organelles, thereby triggering apoptosis. Sophisticated methods (proteomics,
      protein microarray, and super resolution microscopy) have been used for studying
      iAbeta interactions with proteins and membraneous structures. The present review
      summarizes the studies on the origin of iAbeta and the base of its neurotoxicity:
      interactions with cytosolic proteins and several cell organelles such as
      endoplasmic reticulum, endosomes, lysosomes, ribosomes, mitochondria, and the
      microtubular system.

PMID- 23161401
TI  - Application of proteomics to cerebrovascular disease.
AB  - While neurovascular diseases such as ischemic and hemorrhagic stroke are the
      leading causes of disability in the world, the repertoire of therapeutic
      interventions has remained remarkably limited. There is a dire need to develop
      new diagnostic, prognostic, and therapeutic options. The study of proteomics is
      particularly enticing for cerebrovascular diseases such as stroke, which most
      likely involve multiple gene interactions resulting in a wide range of clinical
      phenotypes. Currently, rapidly progressing neuroproteomic techniques have been
      employed in clinical and translational research to help identify biologically
      relevant pathways, to understand cerebrovascular pathophysiology, and to develop
      novel therapeutics and diagnostics. Future integration of proteomic with genomic,
      transcriptomic, and metabolomic studies will add new perspectives to better
      understand the complexities of neurovascular injury. Here, we review
      cerebrovascular proteomics research in both preclinical (animal, cell culture)
      and clinical (blood, urine, cerebrospinal fluid, microdialyates, tissue) studies.
      We will also discuss the rewards, challenges, and future directions for the
      application of proteomics technology to the study of various disease phenotypes.
      To capture the dynamic range of cerebrovascular injury and repair with a
      translational targeted and discovery approach, we emphasize the importance of
      complementing innovative proteomic technology with existing molecular biology
      models in preclinical studies, and the need to advance pharmacoproteomics to
      directly probe clinical physiology and gauge therapeutic efficacy at the bedside.

PMID- 23161403
TI  - A comparative analysis on the synonymous codon usage pattern in viral functional
      genes and their translational initiation region of ASFV.
AB  - The synonymous codon usage pattern of African swine fever virus (ASFV), the
      similarity degree of the synonymous codon usage between this virus and some
      organisms and the synonymous codon usage bias for the translation initiation
      region of viral functional genes in the whole genome of ASFV have been
      investigated by some simply statistical analyses. Although both GC12% (the GC
      content at the first and second codon positions) and GC3% (the GC content at the
      third codon position) of viral functional genes have a large fluctuation, the
      significant correlations between GC12 and GC3% and between GC3% and the first
      principal axis of principle component analysis on the relative synonymous codon
      usage of the viral functional genes imply that mutation pressure of ASFV plays an
      important role in the synonymous codon usage pattern. Turning to the synonymous
      codon usage of this virus, the codons with U/A end predominate in the synonymous
      codon family for the same amino acid and a weak codon usage bias in both leading
      and lagging strands suggests that strand compositional asymmetry does not take
      part in the formation of codon usage in ASFV. The interaction between the
      absolute codon usage bias and GC3% suggests that other selections take part in
      the formation of codon usage, except for the mutation pressure. It is noted that
      the similarity degree of codon usage between ASFV and soft tick is higher than
      that between the virus and the pig, suggesting that the soft tick plays a more
      important role than the pig in the codon usage pattern of ASFV. The translational
      initiation region of the viral functional genes generally have a strong tendency
      to select some synonymous codons with low GC content, suggesting that the
      synonymous codon usage bias caused by translation selection from the host takes
      part in modulating the translation initiation efficiency of ASFV functional
      genes.

PMID- 23161404
TI  - Pharmacological inhibition of GSK3 attenuates DNA damage-induced apoptosis via
      reduction of p53 mitochondrial translocation and Bax oligomerization in
      neuroblastoma SH-SY5Y cells.
AB  - Glycogen synthase kinase-3 (GSK3) and p53 play crucial roles in the mitochondrial
      apoptotic pathway and are known to interact in the nucleus. However, it is not
      known if GSK3 has a regulatory role in the mitochondrial translocation of p53
      that participates in apoptotic signaling following DNA damage. In this study, we
      demonstrated that lithium and SB216763, which are pharmacological inhibitors of
      GSK3, attenuated p53 accumulation and caspase-3 activation, as shown by PARP
      cleavage induced by the DNA-damaging agents doxorubicin, etoposide and
      camptothecin. Furthermore, each of these agents induced translocation of p53 to
      the mitochondria and activated the mitochondrial pathway of apoptosis, as
      evidenced by the release of cytochrome C from the mitochondria. Both
      mitochondrial translocation of p53 and mitochondrial release of cytochrome C were
      attenuated by inhibition of GSK3, indicating that GSK3 promotes the DNA damage
      induced mitochondrial translocation of p53 and the mitochondrial apoptosis
      pathway. Interestingly, the regulation of p53 mitochondrial translocation by GSK3
      was only evident with wild-type p53, not with mutated p53. GSK3 inhibition also
      reduced the phosphorylation of wild-type p53 at serine 33, which is induced by
      doxorubicin, etoposide and camptothecin in the mitochondria. Moreover, inhibition
      of GSK3 reduced etoposide-induced association of p53 with Bcl2 and Bax
      oligomerization. These findings show that GSK3 promotes the mitochondrial
      translocation of p53, enabling its interaction with Bcl2 to allow Bax
      oligomerization and the subsequent release of cytochrome C. This leads to caspase
      activation in the mitochondrial pathway of intrinsic apoptotic signaling.

PMID- 23161405
TI  - Microfluidic synthesis of tail-shaped alginate microparticles using slow
      sedimentation.
AB  - This study reports the synthesis of tail-shaped alginate particles using a
      microfluidic platform combined with a sedimentation strategy. By utilizing
      microfluidic emulsification in the cross-junction channel, the formation of
      regular droplets was achieved. Following a facile and convenient sedimentation
      process and an ionic crosslinking process, sodium-alginate droplets became tail
      shaped and then gradually developed into calcium-alginate microparticles. The
      effects of the concentration of the CaCl(2)  crosslinker and the viscosity of the
      alginate solution on the shape and/or size of the particles were further
      investigated. The proposed synthesis methodology has the advantages of actively
      controlling the tail-shape formation, having a narrow size distribution, as well
      as being a facile and convenient process with a high throughput. This approach
      can be applied to many applications in the pharmaceutical and biomedical arena.

PMID- 23161407
TI  - In vivo measurement of transverse relaxation time in the mouse brain at 17.6 T.
AB  - PURPOSE: To establish regional T1 and T2 values of the healthy mouse brain at
      ultra-high magnetic field strength of 17.6 T and to follow regional brain T1 and
      T2 changes with age. METHODS: In vivo T1 and T2 values in the C57BL/6J mouse
      brain were followed with age using multislice-multiecho sequence and multiple
      spin echo saturation recovery with variable repetition time sequence,
      respectively, at 9.4 and 17.6 T. Gadolinium-tetra-azacyclo-dodecane-tetra-acetic
      acid phantoms were used to validate in vivo T2 measurements. Student's t-test was
      used to compare mean relaxation values. RESULTS: A field-dependent decrease in T2
      is shown and validated with phantom measurements. T2 values at 17.6 T typically
      increased with age in multiple brain regions except in the hypothalamus and the
      caudate-putamen, where a slight decrease was observed. Furthermore, T1 values in
      various brain regions of young and old mice are presented at 17.6 T. A large gain
      in signal-to-noise ratio was observed at 17.6 T. CONCLUSIONS: This study
      establishes for the first time the normative T1 and T2 values at 17.6 T over
      different mouse brain regions with age. The estimates of in vivo T1 and T2 will
      be useful to optimize pulse sequences for optimal image contrast at 17.6 T and
      will serve as baseline values against which disease-related relaxation changes
      can be assessed in mice.

PMID- 23161406
TI  - Integrating cereal genomics to support innovation in the Triticeae.
AB  - The genomic resources of small grain cereals that include some of the most
      important crop species such as wheat, barley, and rye are attaining a level of
      completion that now is contributing to new structural and functional studies as
      well as refining molecular marker development and mapping strategies for
      increasing the efficiency of breeding processes. The integration of new efforts
      to obtain reference sequences in bread wheat and barley, in particular, is
      accelerating the acquisition and interpretation of genome-level analyses in both
      of these major crops.

PMID- 23161408
TI  - Chronic exposure to low concentrations of strontium 90 affects bone physiology
      but not the hematopoietic system in mice.
AB  - The aim of this work was to delineate the effects of chronic ingestion of
      strontium 90 ((90) Sr) at low concentrations on the hematopoiesis and the bone
      physiology. A mouse model was used for that purpose. Parent animals ingested
      water containing 20 kBq l(-1) of (90) Sr two weeks before mating. Offspring were
      then continuously contaminated with (90) Sr through placental transfer during
      fetal life, through lactation after birth and through drinking water after
      weaning. At various ages between birth and 20 weeks, animals were tested for
      hematopoietic parameters such as blood cell counts, colony forming cells in
      spleen and bone marrow and cytokine concentrations in the plasma. However, we did
      not find any modification in (90) Sr ingesting animals as compared with control
      animals. By contrast, the analysis of bone physiology showed a modification of
      gene expression towards bone resorption. This was confirmed by an increase in C
      telopeptide of collagen in the plasma of (90) Sr ingesting animals as compared
      with control animals. This modification in bone metabolism was not linked to a
      modification of the phosphocalcic homeostasis, as measured by calcium,
      phosphorus, vitamin D and parathyroid hormone in the blood. Overall these results
      suggest that the chronic ingestion of (90) Sr at low concentration in the long
      term may induce modifications in bone metabolism but not in hematopoiesis.

PMID- 23161409
TI  - Phase II study of cisplatin and oral VP16 in patients with refractory or relapsed
      Ewing sarcoma.
AB  - BACKGROUND: Phase II trials demonstrate the activity of cisplatin in patients
      with refractory Ewing sarcoma family tumours (ESFT) and also the feasibility of
      giving cisplatin with oral VP16 in a variety of different cancers. This trial was
      conducted to evaluate the activity and toxicity profile of this combination
      delivered as outpatient therapy in patients with refractory/relapsed ESFT.
      METHODS: Cisplatin was administered on days 1, 8 and 15 and days 29, 36 and 43
      (70 mg/m(2)/dose for patients <21 years of age and 50 mg/m(2)/dose >=21 years).
      VP16 was administered at a dose of 50 mg/m(2) on days 1-15 and days 29-43
      inclusive. A three-stage Fleming statistical design was used for analysis.
      RESULTS: Between January 2003 and October 2006, 45 patients aged between 5 and 46
      years (median 19) were enrolled. Thirty-eight were evaluable for response.
      Patients had previously received one to three lines of chemotherapy (median =
      one). Seventy-three per cent of the patients had grade 3/4 neutropenia, 20 %
      developed fever, 40 % had grade 3/4 anaemia, 68 % grade 3/4 thrombocytopenia and
      16 % grade 2/3 ototoxicity. Measured response after 2 cycles: 0 CR, 7 PR (18 %),
      13 SD (34 %), 18 PD (48 %). There was excellent concordance between
      unidimensional and bidimensional criteria in 31 of 33 responses (94 %). PFS at 1
      year was 39 %, with a median PFS of 6 months. Overall survival at 1 year was 44
      %; median survival was 11 months. CONCLUSIONS: Cisplatin combined with oral VP16
      is well tolerated and has acceptable side effects, but limited clinical activity
      in refractory/relapsed ESFT.

PMID- 23161410
TI  - Combination of three cytotoxic agents in small-cell lung cancer.
AB  - PURPOSE: The established treatment for small-cell lung cancer has been a
      cisplatin-etoposide combination, as the most effective chemotherapy regimen.
      Paclitaxel has also been used in combination with cisplatin and etoposide but
      this has been unacceptable due to the toxicity. This toxicity could be attributed
      to the three consequent days of treatment with etoposide plus the doses of each
      of the three drugs. Our objectives were to determine an equal or longer survival
      and lower toxicity by administering all 3 drugs with low dosage on day one,
      compared to the established guideline of 3-day administration. METHODS: We tested
      the aforementioned three-drug combination and avoided the toxicity in the
      majority of patients by administering all 3 drugs on day one. Fifty-one patients
      (50 evaluable) were recruited from 4 oncology clinics. All patients had
      histologically or cytologically confirmed small-cell lung cancer with limited and
      extensive disease in 40 and 60 % of the patients, respectively. The treatment
      was: cisplatin 75 mg/m(2), etoposide 120 mg/m(2) (maximum 200 mg), and paclitaxel
      135 mg/m(2). The agents were administered on day one and repeated every 3 weeks
      for 6 cycles. RESULTS: The median survival was 15 months (95 % CI 13.6-16.4)
      (mean 16 months). Forty-five (90 %) patients achieved a response: 20 (40 %)
      patients, a complete response and 25 (50 %), a partial response. Adverse
      reactions included grade 3 and 4 neutropenia in 12 and 2 % of the patients,
      respectively. Other side effects were of very low toxicity. CONCLUSION: The 1
      day, three-agent (cisplatin-etoposide-paclitaxel) treatment of small-cell lung
      cancer is beneficial with respect to response rate and survival, and the toxicity
      is low and well-tolerated.

PMID- 23161411
TI  - Association between bevacizumab-related hypertension and vascular endothelial
      growth factor (VEGF) gene polymorphisms in Japanese patients with metastatic
      colorectal cancer.
AB  - PURPOSE: Bevacizumab, a monoclonal antibody that binds to VEGF, has a well-known
      toxic effect of hypertension. We studied possible associations between
      bevacizumab-related hypertension and gene polymorphisms to assure safer cancer
      therapy. METHODS: We retrospectively studied 60 Japanese patients with metastatic
      colorectal cancer who had received bevacizumab-based chemotherapy. Genotypes were
      determined for five well-known functional single-nucleotide polymorphism of the
      VEGF gene at positions C-2578A, T-1498C, G-1154A, G-634C, and C936T. Hypertension
      was graded according to CTCAE v4.0 on the basis of home blood pressure. RESULTS:
      The VEGF-2578 C/C and -1498 T/T genotypes were associated with significantly less
      hypertension during the first 2 months of bevacizumab-based chemotherapy (p =
      0.004, p = 0.025, respectively). During the treatment period as a whole, the VEGF
      2578 C/C and 936 C/C genotypes were associated with less hypertension (p = 0.031,
      p = 0.043, respectively). Preexisting hypertension was not associated with
      bevacizumab-related hypertension. CONCLUSIONS: This study demonstrated a
      significant relation between a lower incidence of grade 2 or higher bevacizumab
      related hypertension and the VEGF-2578 C/C genotype for the entire treatment
      period in Japanese patients with metastatic colorectal cancer. This genotype
      might be useful for ensuring safer treatment of patients who receive bevacizumab
      based chemotherapy.

PMID- 23161412
TI  - A multicellular signal transduction network of AGE/RAGE signaling.

PMID- 23161413
TI  - Phosphoinositide-specific Phospholipase C beta1 gene deletion in bipolar disorder
      affected patient.
AB  - The involvement of phosphoinositides (PI) signal transduction pathway and related
      molecules, such as the Phosphoinositide-specific Phospholipase C (PI-PLC)
      enzymes, in the pathophysiology of mood disorders is corroborated by a number of
      recent evidences. Our previous works identified the deletion of PLCB1 gene, which
      codifies for the PI-PLC beta1 enzyme, in 4 out 15 patients affected with
      schizophrenia, and no deletion both in major depression affected patients and in
      normal controls. By using interphase fluorescent in situ hybridization
      methodology, we analyzed PLCB1 in paraffin embedded samples of orbito-frontal
      cortex of 15 patients affected with bipolar disorder. Deletion of PLCB1 was
      identified in one female patient.

PMID- 23161414
TI  - LPS and PAN-induced podocyte injury in an in vitro model of minimal change
      disease: changes in TLR profile.
AB  - Minimal change disease (MCD), the most common idiopathic nephrotic syndrome in
      children, is characterized by proteinuria and loss of glomerular visceral
      epithelial cell (podocyte) ultrastructure. Lipopolysaccharide (LPS) and puromycin
      aminonucleoside (PAN) are used to study podocyte injury in models of MCD in vivo
      and in vitro. We hypothesized that LPS and PAN influence components of the innate
      immune system in podocytes such as the Toll-Like Receptor (TLRs), TLR adapter
      molecules, and associated cytokines. Our results show that cultured human
      podocytes constitutively express TLRs 1-6 and TLR-10, but not TLRs 7-9. LPS (25
      MUg/ml) or PAN (60 MUg/ml) caused comparable derangement of the actin
      cytoskeleton in podocytes. Quantitative RT-PCR analysis show that LPS
      differentially up-regulated the expression of genes for TLRs (1 > 4 >= 2 > 3 > 6
      > 5), the adapter molecule, MyD88, and transcription factor NF-kappaB within one
      hour. LPS also caused increased levels of IL-6, IL-8 and MCP1 without exerting
      any effect on TNF-alpha, IFN-alpha or TGF-beta1 at 24 h. Immunofluorescence
      intensity analysis of confocal microscopy images showed that LPS induced a
      significant increase in nuclear translocation of NF-kappaB by 6 h. In contrast,
      PAN-induced only small changes in the expression of TLRs 2-6 that included a
      persistent increase in TLRs 2 and 5, a transient increase in TLR-4, and a gradual
      increase in TLRs 3 and 6 between 1 and 6 h. Correspondingly, it did not alter pro
      inflammatory cytokine levels in podocytes. However, PAN induced a low but
      significant increase in NF-kappaB nuclear translocation within one hour that
      remained unchanged up to 6 h. In summary, these novel findings show that LPS, a
      known TLR-4 ligand, induced the gene expression of multiple TLRs with maximum
      effect on the expression of TLR-1 suggesting a loss of receptor selectivity and
      induction of receptor interactions in podocytes. A comparable derangement of the
      podocyte cytoskeleton and significant increase in the nuclear translocation of NF
      kappaB by PAN suggest that disparate but complementary mechanisms may contribute
      to the development of podocytopathy in MCD.

PMID- 23161415
TI  - Post-traumatic high thoracic angular kyphosis: posterior approach with correction
      and fusion in two steps.

PMID- 23161416
TI  - Sagittal alignment correction and reconstruction of lumbar  post-traumatic
      kyphosis via MIS lateral approach.

PMID- 23161417
TI  - Lumbar hemivertebra resection by posterior approach for congenital scoliosis.

PMID- 23161418
TI  - Unilateral atlantal lateral mass hypertrophy associated with atlanto-occipital
      fusion.
AB  - PURPOSE: Unilateral hypertrophy of the lateral mass of the atlas is an extremely
      rare condition. The authors present a rare type of unilateral atlantal mass
      hypertrophy with atlanto-occipital fusion which is associated with an invaginated
      lateral mass of the atlas and the odontoid process into the foramen magnum.
      METHODS: A 45-year-old woman presented with a 2-year history of progressive
      bilateral weakness in the upper and lower extremities and gait disturbance. The
      left lateral mass of the atlas was hypertrophied and had invaginated into the
      foramen magnum with the odontoid. The spinal cord was severely compressed at the
      level of the foramen magnum, surrounded by the lateral mass of the atlas, the
      odontoid process and the occipital bone. RESULTS: First, ventral decompression
      was performed using a transmandibular approach. The anterior arch of the atlas,
      the medial side of the hypertrophied lateral mass and the odontoid process were
      resected. Two weeks after primary surgery, posterior occipitocervical fusion was
      performed. The postoperative course of the patient was uneventful. Three years
      after the operation, she could walk without assistance and her paresthesia
      improved. CONCLUSIONS: To our knowledge, such a case of unilateral atlantal mass
      hypertrophy associated with atlanto-occipital fusion has not been described
      previously. The authors discuss the pathology of this case and review the
      literature on unilateral atlantal mass hypertrophy and associated anomalies of
      the upper cervical spine.

PMID- 23161419
TI  - Relevance of intraoperative D wave in spine and spinal cord surgeries.
AB  - PURPOSE: The combined recordings of epidural-(D wave) and muscle motor evoked
      potentials (m-MEPs) have been proposed in many studies in intramedullary spinal
      cord tumour (IMSCT) surgery, although not all agree. Furthermore, the usefulness
      of the intraoperative monitoring of motor systems using these methods in other
      types of spine surgery has not yet been clearly confirmed. The aim of this study
      is to test the impact of intraoperative D wave on the monitorability and motor
      outcome in spine surgery. METHODS: Intraoperative recording of posterior tibial
      nerve somatosensory potentials, lower limb m-MEPs (LLm-MEPs) and epidurally
      recorded D wave caudally to the surgical level was attempted in a total of 103
      spine and spinal cord surgeries (23 IMSCT, 55 extramedullary spinal cord tumours
      and 25 myelopathies). RESULTS: There was a 97.1 %, overall monitorability where
      at least 1 of the 3 modalities was applicable in 100 surgical procedures.
      Baseline LLm-MEPs were recorded bilaterally in 85 cases and unilaterally in 11. A
      caudal D wave was recorded in 97 cases. Transient, or persistent intraoperative
      modifications occurred in 14/23 IMSCT, 5/55 extramedullary spinal cord tumours
      and in 2/25 myelopathies. The presence of a persistent stable caudal D wave was
      predictive of a good motor outcome even when the LL-MEPs were absent and/or when
      lost during surgery. CONCLUSIONS: Not only is intraoperative D wave recording to
      be considered mandatory in IMSCT surgery but it should also be attempted in other
      types of spine/spinal cord surgeries.

PMID- 23161420
TI  - Management of hangman's fracture with percutaneous transpedicular screw fixation.
AB  - PURPOSE: This study describes a percutaneous technique for C2 transpedicular
      screw fixation and evaluates its safety and efficacy in the treatment of patients
      with hangman's fracture. METHODS: Ten patients with hangman's fracture were
      treated by percutaneous C2 transpedicular screw fixation. There are six males and
      four females, who were, based on the classification of Levine and Edwards, sorted
      as follows: type I fracture, three cases; type II, five cases; type IIa, two
      cases. The causes of injury were road traffic accident in six patients and
      falling injury in four patients. Other associated lesions included rib fractures
      (7 patients), head injuries (4 patients), and fractures of extremities (6
      patients). RESULTS: The new technique was performed successfully in all cases.
      The average operation time was 98 min (range 60-130 min) and the estimated blood
      loss was 25 ml (range 15-40 ml). No complications such as vascular or neural
      structures injuries were found intraoperatively. Postoperative CT scans
      demonstrated that 17 (85 %) of 20 screws were placed satisfactorily, and 3 (15 %)
      screws showed perforations of the pedicle wall (<2 mm). These patients were
      asymptomatic and no further intervention was required postoperatively. After 8-25
      months follow-up (mean 15.3 months), solid fusion was demonstrated by computed
      tomography. All cases got well-sagittal alignment and no angulation or
      dislocation was found at the segment of C2-C3. There was no loss of fixation.
      Clinical examination showed a full range of motion in the neck in all patients.
      CONCLUSIONS: The fluoroscopically assisted percutaneous C2 transpedicular screw
      fixation method is a technically feasible and minimally invasive technique for
      hangman's fracture.

PMID- 23161421
TI  - Cervical osteotomy in Ankylosing Spondylitis.

PMID- 23161424
TI  - Topoisomerase I inhibitor evodiamine acts as an antibacterial agent against drug
      resistant Klebsiella pneumoniae.
AB  - Topoisomerase inhibitors have been developed in a variety of clinical
      applications. We investigated the inhibitory effect of evodiamine on E. coli
      topoisomerase I, which may lead to an anti-bacterial effect. Evodiamine inhibits
      the supercoiled plasmid DNA relaxation that is catalyzed by E. coli topoisomerase
      I, and computer-aided docking has shown that the Arg161 and Asp551 residues of
      topoisomerase I interact with evodiamine. We investigated the bactericidal effect
      of evodiamine against multidrug-resistant Klebsiella pneumoniae. Evodiamine
      showed a significantly lower minimal inhibitory concentration value (MIC 128
      ug/mL) compared with antibiotics (>512 ug/mL) against the clinical isolate of K.
      pneumoniae. The results suggested that evodiamine is a potential agent against
      drug-resistant bacteria.

PMID- 23161422
TI  - Solid-phase extraction of nitrophenols in water by using a combination of carbon
      nanotubes with an ionic liquid coupled in-line to CE.
AB  - This paper describes the combined use of carbon nanotubes and an ionic liquid
      directly coupled in-line to commercial CE equipment for sample treatment. The
      extraction unit operates as a spin column to preconcentrate the analytes. The
      extraction unit is inserted into the sample vial. The elution is performed in
      line, placing the vial on the carrousel of the CE equipment. The joint use of
      carbon nanotubes and ionic liquids as sorbent is based on the high adsorption
      capacity of these materials, which makes them highly suitable for microextraction
      purposes. The LOQ of analytes were within the range of 0.65-0.83 MUg/L with a RSD
      of less than 7%. The values of recovery range between 90 and 112%. The absolute
      recovery obtained from samples containing 1 MUg/L of analytes was 38%.

PMID- 23161425
TI  - Detection and quantification of pyrrolizidine alkaloids in antibacterial medical
      honeys.
AB  - In recent years, there has been an increasing interest in antibacterial honey for
      wound care ranging from minor abrasions and burns to leg ulcers and surgical
      wounds. On the other hand, several recent studies demonstrated that honey for
      human consumption was contaminated with natural occurring, plant derived
      pyrrolizidine alkaloids.1,2-Unsaturated pyrrolizidine alkaloids are a group of
      secondary plant metabolites that show developmental, hepato-, and geno-toxicity
      as well as carcinogenic effects in animal models and in in vitro test systems.
      Hence, it was of particular interest to analyze the pyrrolizidine alkaloid
      content of medical honeys intended for wound care.19 different medical honey
      samples and/or batches were analyzed by applying a recently established
      pyrrolizidine alkaloid sum parameter method. 1,2-Unsaturated pyrrolizidine
      alkaloids were converted into the common necin backbone structures and were
      analyzed and quantified by GC-MS in the selected ion monitoring mode.All but one
      medical honey analyzed were pyrrolizidine alkaloid positive. The results ranged
      from 10.6 ug retronecine equivalents per kg to 494.5 ug retronecine
      equivalents/kg medical honey. The average pyrrolizidine alkaloid content of all
      positive samples was 83.6 ug retronecine equivalents/kg medical honey (average of
      all samples was 79.3 ug retronecine equivalents/kg medical honey). The limit of
      detection was 2.0 ug retronecine equivalents/kg medical honey, while the limit of
      quantification was 6.0 ug retronecine equivalents/kg medical honey (S/N >
      7/1).Based on the data presented here and considering the fact that medical
      honeys can be applied to open wounds, it seems reasonable to discuss the
      monitoring of 1,2-unsaturated pyrrolizidine alkaloids in honey intended for wound
      treatment.

PMID- 23161426
TI  - Cycloartanes from Krameria pauciflora and their in vitro PLA2, COX-1, and COX-2
      enzyme inhibitory activities.
AB  - Krameria pauciflora is a species belonging to the Krameriaceae family. It has
      been used to treat inflammatory disorders in folkloric Mexican medicine; however,
      chemistry and pharmacological studies have not been carried out on this species.
      In this work, from the dichloromethane root extract of K. pauciflora, five
      cycloartane-type triterpenoids were isolated: cyclomargenyl-3-O-beta-caffeoyl
      ester (1), cyclomargenyl-3-O-beta-feruloyl ester (2), cyclomargenyl-3-O-beta
      coumaroyl ester (3), cyclomargenol (4, polysthicol), and cyclomargenone (5).
      Additionally, the lignane 6'-methoxyrataniaphenol was isolated. To the best of
      our knowledge, compounds 1-3 are new natural products, whereas compounds 4 and 5
      are isolated for the first time in the Krameria genus and the Krameriaceae
      family. The structures of all of these compounds were established by 1D and 2D
      NMR spectroscopy including 1H, 13C, DEPT, COSY, HSQC, and HMBC experiments, as
      well as by EI mass spectrometry. There is an incomplete previous report about the
      spectroscopic data of compounds 4 and 5. However, in this work, a complete and
      unambiguous assignation has been realized. Due to the traditional use of this
      plant and other species from this genus, such as K. lappacea, cycloartanes
      isolated herein were evaluated by their inhibition of phospholipase A2,
      cyclooxygenase-1, and cyclooxygenase-2 enzymes. Cyclomargenyl-3-O-beta-caffeoyl
      ester (1) showed inhibition of phospholipase A2, cyclooxygenase-1, and
      cyclooxygenase-2 target enzymes for nonsteroidal anti-inflammatory drugs. Both
      cyclooxygenases were inhibited by cyclomargenol (4); however, cyclomargenyl-3-O
      beta-feruloyl ester (2) showed inhibition only on cyclooxygenase-1.

PMID- 23161427
TI  - Ilexpublesnins C-M, eleven new triterpene saponins from the roots of Ilex
      pubescens.
AB  - Eleven new triterpene saponins, ilexpublesnins C-M (1-11), along with ten known
      analogues were isolated from the roots of Ilex pubescens. Their structures were
      elucidated on the basis of extensive spectroscopic analysis, including 1D and 2D
      NMR experiments. Compounds 1, 2, 10, and 11 contain a 24-aldehyde, which is rare
      for triterpene saponins from Ilex. These compounds were evaluated in vitro for
      their cytotoxic effects on human cancer cell lines HepG2, HLE, BEL7402, BEL7403,
      BEL7405, MCF-7, and HeLa. Among them, only compounds 6 and 19 showed cytotoxicity
      against the MCF-7 cell line [inhibition (%): 33.14 and 34.03, respectively].

PMID- 23161428
TI  - Perceptual representations of phonotactically illegal syllables.
AB  - Listeners often categorize phonotactically illegal sequences (e.g., /dla/ in
      English) as phonemically similar legal ones (e.g., /gla/). In an earlier
      investigation of such an effect in Japanese, Dehaene-Lambertz, Dupoux, and Gout
      (2000) did not observe a mismatch negativity in response to deviant, illegal
      sequences, and therefore argued that phonotactics constrain early perceptual
      processing. In the present study, using a priming paradigm, we compared the event
      related potentials elicited by Legal targets (e.g., /gla/) preceded by (1)
      phonemically distinct Control primes (e.g., /kla/), (2) different tokens of
      Identity primes (e.g., /gla/), and (3) phonotactically Illegal Test primes (e.g.,
      /dla/). Targets elicited a larger positivity 200-350 ms after onset when preceded
      by Illegal Test primes or phonemically distinct Control primes, as compared to
      Identity primes. Later portions of the waveforms (350-600 ms) did not differ for
      targets preceded by Identity and Illegal Test primes, and the similarity ratings
      also did not differ in these conditions. These data support a model of speech
      perception in which veridical representations of phoneme sequences are not only
      generated during processing, but also are maintained in a manner that affects
      perceptual processing of subsequent speech sounds.

PMID- 23161429
TI  - Add-on therapy of pitavastatin and eicosapentaenoic acid improves outcome of
      peginterferon plus ribavirin treatment for chronic hepatitis C.
AB  - Despite the use of pegylated-interferon (peg-IFN) plus ribavirin combination
      therapy, many patients infected with hepatitis C virus (HCV)-1b remain HCV
      positive. To determine whether addition of pitavastatin and eicosapentaenoic acid
      (EPA) is beneficial, the "add-on" therapy option (add-on group) was compared
      retrospectively with unmodified peg-IFN/ribavirin therapy (standard group).
      Association of host- or virus-related factors with sustained virological response
      was assessed. In HCV replicon cells, the effects of pitavastatin and/or EPA on
      HCV replication and expression of innate-immunity- and lipid-metabolism
      associated genes were investigated. In patients infected with HCV-1b, sustained
      virological response rates were significantly higher in the add-on than standard
      group. In both groups, sustained virological response rates were significantly
      higher in patients with genotype TT of IL-28B (rs8099917) than in those with non
      TT genotype. Among the patients with non-TT genotype, sustained virological
      response rates were markedly higher in the add-on than standard group. By
      multivariate analysis, genome variation of IL28B but not add-on therapy remained
      as a predictive factor of sustained virological response. In replicon cells,
      pitavastatin and EPA suppressed HCV replication. Activation of innate immunity
      was obvious in pitavastatin-treated cells and EPA suppressed the expression of
      sterol regulatory element binding protein-1c and low-density lipoprotein
      receptor. Addition of pitavastatin and EPA to peg-IFN/ribavirin treatment
      improved sustained virological response in patients infected with HCV-1b.
      Genotype variation of IL-28B is a strong predictive factor in add-on therapy.

PMID- 23161431
TI  - Determination of UV filters in river water samples by in-line SPE-CE-MS.
AB  - The use of SPE coupled in-line to CE using electrospray MS detection (in-line SPE
      CE-ESI-MS) was investigated for the preconcentration and separation of four UV
      filters: benzophenone-3, 2,2-dihydroxy-4-methoxybenzophenone, 2,4
      dihydroxybenzophenone and 2-phenylbenzimidazole-5-sulphonic acid. First, a CE-ESI
      MS method was developed and validated using standard samples, obtaining LODs
      between 0.06 MUg/mL and 0.40 MUg/mL. For the in-line SPE-CE-ESI-MS method, three
      different sorbents were evaluated and compared: Oasis HLB, Oasis MCX, and Oasis
      MAX. For each sorbent, the main parameters affecting the preconcentration
      performance, such as sample pH, volume, and composition of the elution plug, and
      sample injection time were studied. The Oasis MCX sorbent showed the best
      performance and was used to validate the in-line SPE-CE-ESI-MS methodology. The
      LODs reached for standard samples were in the range between 0.01 and 0.05 ng/mL
      with good reproducibility and the developed strategy provided sensitivity
      enhancement factors between 3400-fold and 34 000-fold. The applicability of the
      developed methodology was demonstrated by the analysis of UV filters in river
      water samples.

PMID- 23161430
TI  - Pathways from religion to advance care planning: beliefs about control over
      length of life and end-of-life values.
AB  - PURPOSE OF THE STUDY: To evaluate the extent to which religious affiliation and
      self-identified religious importance affect advance care planning (ACP) via
      beliefs about control over life length and end-of-life values. DESIGN AND
      METHODS: Three hundred and five adults aged 55 and older from diverse racial and
      socioeconomic groups seeking outpatient care in New Jersey were surveyed.
      Measures included discussion of end-of-life preferences; living will (LW)
      completion; durable power of attorney for healthcare (DPAHC) appointment;
      religious affiliation; importance of religion; and beliefs about who/what
      controls life length, end-of-life values, health status, and sociodemographics.
      RESULTS: Of the sample, 68.9% had an informal discussion and 46.2% both discussed
      their preferences and did formal ACP (LW and/or DPAHC). Conservative Protestants
      and those placing great importance on religion/spirituality had a lower
      likelihood of ACP. These associations were largely accounted for by beliefs about
      God's controlling life length and values for using all available treatments.
      IMPLICATIONS: Beliefs and values about control account for relationships between
      religiosity and ACP. Beliefs and some values differ by religious affiliation. As
      such, congregations may be one nonclinical setting in which ACP discussions could
      be held, as individuals with similar attitudes toward the end of life could
      discuss their treatment preferences with those who share their views.

PMID- 23161432
TI  - The interplay of environmental toxicology and chemistry in the development of
      sediment quality criteria.

PMID- 23161433
TI  - A conformational heparan sulfate binding site essential to infectivity overlaps
      with the conserved hepatitis B virus a-determinant.
AB  - Two determinants of infectivity have been identified in the hepatitis B virus
      (HBV) envelope proteins: a pre-S1 receptor-binding site and an uncharacterized
      determinant in the antigenic loop (AGL), which is structurally related to the
      antigenic a-determinant. Infection would proceed through virus attachment to cell
      surface heparan sulfate (HS) proteoglycans (HSPGs) before pre-S1 engages a
      specific receptor for uptake. Using heparin binding and in vitro infection assays
      with hepatitis D virus as a surrogate for HBV, we established that HS binding is
      mediated by the AGL. Electrostatic interaction was shown to depend upon AGL
      residues R122 and K141, because their substitution with alanine modified the
      virus net-charge and prevented binding to heparin, attachment to hepatocytes, and
      infection. In addition to R122 and K141, the HS binding determinant was mapped to
      cysteines and prolines, which also define the conformational a-determinant. The
      importance of AGL conformation was further demonstrated by the concomitant loss
      of a-determinant and heparin binding upon treatment of viral particles with
      membrane-impermeable reducing agent. Furthermore, envelope proteins extracted
      from the viral membrane with a nonionic detergent were shown to conserve the a
      determinant but to lose heparin affinity/avidity. CONCLUSION: Our findings
      support a model in which attachment of HBV to HSPGs is mediated by the AGL HS
      binding site, including only two positively charged residues (R122 and K141)
      positioned precisely in a three-dimensional AGL structure that is stabilized by
      disulfide bonds. HBV envelope proteins would individually bind to HS with low
      affinity, but upon their clustering in the viral membrane, they would reach
      sufficient avidity for a stable interaction between virus and cell surface HSPGs.
      Our data provide new insight into the HBV entry pathway, including the
      opportunity to design antivirals directed to the AGL-HS interaction.

PMID- 23161435
TI  - Glycoproteomics on the rise: established methods, advanced techniques,
      sophisticated biological applications.
AB  - Glycosylation is the most complex form of protein PTMs. Affected proteins may
      carry dozens of glycosylation sites with tens to hundreds of glycan residues
      attached to every site. Glycosylated proteins have many important functions in
      biology, from cellular to organismal levels, being involved in cell-cell
      signaling, cell adhesion, immune response, host-pathogen interactions, and
      development and growth. Glycosylation, however, expands the biological functional
      diversity of proteins at the expense of a tremendous increase in structural
      heterogeneity. Aberrant glycosylation of cell surface proteins, as well as their
      detectable fingerprint in plasma samples, has been associated with cancer,
      inflammatory and degenerative diseases, and congenital disorders of
      glycosylation. Therefore, there are on-going efforts directed toward developing
      new technologies and approaches for glycan sequencing and high-throughput
      analysis of glycosylated proteins in complex samples with simultaneous
      characterization of both the protein and glycan moieties. This work is aimed
      primarily at pinpointing the challenges associated with the large-scale analysis
      of glycoproteins and the latest developments in glycoproteomic research, with
      focus on recent advancements (2011-2012) in microcolumn separations and MS
      detection.

PMID- 23161434
TI  - Fat confounds the observed apparent diffusion coefficient in patients with
      hepatic steatosis.
AB  - PURPOSE: Triglyceride signal contained in peaks near the water peak remains
      unsuppressed by conventional fat suppression techniques used in diffusion
      weighted imaging. In this work, we investigated the dependence of the apparent
      diffusion coefficient (ADC) on liver fat content and whether it is confounded by
      fat signal. METHODS: 43 patients underwent liver diffusion-weighted imaging (b =
      0, 500 s/mm(2)) and single-voxel MR-spectroscopy. Proton density fat-fraction
      (PDFF; range 0.23-34.5%) was measured from MR-spectroscopy. A theoretical model
      was developed to account for the effects of fat on observed ADC, and used to
      correct the ADC. Linear correlation analysis was performed to assess the
      relationship between PDFF and ADC before and after correction. RESULTS: Linear
      correlation analysis showed an inverse dependence between observed ADC and PDFF
      before correction (r(2) = 0.132; P = 0.017), and no dependence after correction
      (r(2) = 0.033; P = 0.24). CONCLUSION: The observed decrease in ADC in patients
      with fatty liver is, at least in part, artifactual due to residual fat signal
      near the water peak.

PMID- 23161436
TI  - Notch1 modulates mesenchymal stem cells mediated regulatory T-cell induction.
AB  - Notch1 signaling is involved in regulatory T (Treg)-cell differentiation. We
      previously demonstrated that, when cocultured with CD3(+)  cells, mesenchymal
      stem cells (MSCs) induced a T-cell population with a regulatory phenotype. Here,
      we investigated the molecular mechanism underlying MSC induction of human Treg
      cells. We show that the Notch1 pathway is activated in CD4(+)  T cells cocultured
      with MSCs. Inhibition of Notch1 signaling through GSI-I or the Notch1
      neutralizing antibody reduced expression of HES1 (the Notch1 downstream target)
      and the percentage of MSC-induced CD4(+) CD25(high) FOXP3(+)  cells in vitro.
      Moreover, we demonstrate that FOXP3 is a downstream target of Notch signaling in
      human cells. No crosstalk between Notch1 and TGF-beta signaling pathways was
      observed in our experimental system. Together, these findings indicate that
      activation of the Notch1 pathway is a novel mechanism in the human Treg-cell
      induction mediated by MSCs.

PMID- 23161437
TI  - Enhanced thermal conductivity of epoxy-graphene composites by using non-oxidized
      graphene flakes with non-covalent functionalization.
AB  - Homogeneous distribution of graphene flakes in a polymer matrix, still preserving
      intrinsic material properties, is key to successful composite applications. A
      novel approach is presented to disperse non-oxidized graphene flakes with non
      covalent functionalization of 1-pyrenebutyric acid and to fabricate
      nanocomposites with outstanding thermal conductivity (~1.53 W/mK) and mechanical
      properties (~1.03 GPa).

PMID- 23161438
TI  - Radial nerve cord protein phosphorylation dynamics during starfish arm tip wound
      healing events.
AB  - Echinoderms, as invertebrate deuterostomes, have amazing neuronal intrinsic
      growth aptitude triggered at any time point during the animal lifespan leading to
      successful functional tissue regrowth. This trait is known to be in opposition to
      their mammal close phylogenic relatives that have lost the ability to regenerate
      their central nervous system. Despite the promising nature of this intrinsic
      echinoderm trait, it was only recently that this complex biological event started
      to be unveiled. In the present study, a 2DE gel-based phosphoproteomics approach
      was used to investigate changes in starfish neuronal protein phosphorylation
      states at two different wound healing time-graded events following arm tip
      amputation, 48 h and 13 days. Among the resolved protein spots in 3.0-5.6 NL pH
      IEF strips, 190, 142, and 124 had a phosphoprotein signal in the control and the
      two injury experimental groups, respectively. Gel image analysis, highlighted 129
      spots with an injury-related protein phosphorylation dynamics, several being
      exclusively phosphorylated in controls (72 spots), injured nerves (8 spots) or,
      showing significantly different phosphorylation ratios (37 spots). Within these,
      a total of 43 proteins were identified with MALDI-TOF/TOF. Altogether, several
      intervening proteins of important injury-signaling pathways that seem to be
      modulated through phosphorylation, were identified for the first time in starfish
      radial nerve cord early regeneration events. These include cytoskeleton re
      organization toward the formation of the neuronal growth cones; cell membrane
      rearrangements, actin filaments, and microtubules dynamics; mRNA binding and
      transport; lipid signaling; Notch pathway; and neuropeptide processing.

PMID- 23161439
TI  - Dynamic forceps-assisted vaginal anoscopy for entero-recto-cystocele.

PMID- 23161440
TI  - New trends in management of colorectal cancer.

PMID- 23161441
TI  - Polymorphisms in the Selenoprotein S gene and subclinical cardiovascular disease
      in the Diabetes Heart Study.
AB  - Selenoprotein S (SelS) has previously been associated with a range of
      inflammatory markers, particularly in the context of cardiovascular disease
      (CVD). The aim of this study was to examine the role of SELS genetic variants in
      risk for subclinical CVD and mortality in individuals with type 2 diabetes
      mellitus (T2DM). The association between 10 polymorphisms tagging SELS and
      coronary (CAC), carotid (CarCP) and abdominal aortic calcified plaque, carotid
      intima media thickness and other known CVD risk factors was examined in 1220
      European Americans from the family-based Diabetes Heart Study. The strongest
      evidence of association for SELS SNPs was observed for CarCP; rs28665122 (5'
      region; beta = 0.329, p = 0.044), rs4965814 (intron 5; beta = 0.329, p = 0.036),
      rs28628459 (3' region; beta = 0.331, p = 0.039) and rs7178239 (downstream; beta =
      0.375, p = 0.016) were all associated. In addition, rs12917258 (intron 5) was
      associated with CAC (beta = -0.230, p = 0.032), and rs4965814, rs28628459 and
      rs9806366 were all associated with self-reported history of prior CVD (p = 0.020
      0.043). These results suggest a potential role for the SELS region in the
      development subclinical CVD in this sample enriched for T2DM. Further
      understanding the mechanisms underpinning these relationships may prove important
      in predicting and managing CVD complications in T2DM.

PMID- 23161443
TI  - Uteroplacental ischemia in early- and late-onset pre-eclampsia: a role for the
      fetus?

PMID- 23161442
TI  - PPARG2 Pro12Ala and ADAMTS9 rs4607103 as "insulin resistance loci" and "insulin
      secretion loci" in Italian individuals. The GENFIEV study and the Verona Newly
      Diagnosed Type 2 Diabetes Study (VNDS) 4.
AB  - We investigated cross-sectionally whether the type 2 diabetes (T2DM) risk alleles
      of rs1801282 (PPARG2) and rs4607103 (ADAMTS9) were associated with T2DM and/or
      insulin sensitivity (IS) and beta cell function (betaF) in Italians without and
      with newly diagnosed T2DM. In 676 nondiabetic subjects (336 NGR and 340 IGR) from
      the GENFIEV study and in 597 patients from the Verona Newly Diagnosed Type 2
      Diabetes Study (VNDS), we (1) genotyped rs1801282 and rs4607103, (2) assessed
      betaF by C-peptide/glucose modeling after OGTT, and (3) assessed IS by HOMA-IR in
      both studies and by euglycemic insulin clamp in VNDS only. Logistic, linear, and
      two-stage least squares regression analyses were used to test (a) genetic
      associations with T2DM and with pathophysiological phenotypes, (b) causal
      relationships of the latter ones with T2DM by a Mendelian randomization design.
      Both SNPs were associated with T2DM. The rs4607103 risk allele was associated to
      impaired betaF (p < 0.01) in the GENFIEV study and in both cohorts combined. The
      rs1801282 genotype was associated with IS both in the GENFIEV study (p < 0.03)
      and in the VNDS (p < 0.03), whereas rs4607103 did so in the VNDS only (p = 0.01).
      In a Mendelian randomization design, both HOMA-IR (instrumental variables:
      rs1801282, rs4607103) and betaF (instrumental variable: rs4607103) were related
      to T2DM (p < 0.03-0.01 and p < 0.03, respectively). PPARG2 and ADAMTS9 variants
      are both associated with T2DM and with insulin resistance, whereas only ADAMTS9
      may be related to betaF. Thus, at least in Italians, they may be considered bona
      fide "insulin resistance genes".

PMID- 23161444
TI  - Test/retest repeatability of effect contralateral acoustic stimulation on the
      magnitudes of distortion product ototacoustic emissions.
AB  - OBJECTIVES/HYPOTHESIS: Contralateral inhibition of distortion product otoacoustic
      emissions (DPOAE) has become an important tool to assess the functioning of the
      medial olivocochlear efferents in humans. However, before this measurement can be
      applied clinically, the test/retest repeatability needs to be established.
      Therefore, the current study aimed at evaluating intra- and intersession
      test/retest repeatability of contralateral inhibition of DPOAE at 2f(1) -f(2) .
      STUDY DESIGN: Prospective Test/Retest Reliability Study. METHODS: Contralateral
      inhibition of DPOAE magnitudes were measured in the right ear of 24 adult male
      participants. To assess the intrasession repeatability, measurements were
      repeated without altering the position of the DPOAE probe (single-probe-fit). To
      assess intersession reliability, measurements were repeated on 8 different days
      (multiple-probe-fit). Repeatability of inhibition of DPOAE magnitudes was
      evaluated by Cronbach's alpha, interclass correlations, standard error of
      measurement, and its 95% confidence interval and smallest detectable difference.
      RESULTS: DPOAE magnitudes were highly stable and repeatable across different
      recording sessions. However, test/retest reliability coefficients of DPOAE
      inhibition magnitudes were less than satisfactory for all the frequencies, in
      both single-probe-fit and multiple-probe-fit modes. CONCLUSIONS: Results of the
      present study showed that contralateral inhibition magnitudes of DPOAEs varied
      considerably, even though DPOAEs magnitudes remained essentially the same across
      different recording sessions. As reliability is an essential aspect of any
      clinical procedure, it is suggested that at present contralateral inhibition of
      DPOAEs should not be used clinically to evaluate the medial efferent system.
      Laryngoscope, 2012.

PMID- 23161446
TI  - Prevalence and molecular epidemiology of human coronavirus HKU1 in patients with
      acute respiratory illness.
AB  - In 2005, human coronavirus HKU1 (HCoV-HKU1) was isolated and identified from a 71
      year-old man with pneumonia in Hong Kong. To identify and classify genotypes of
      HCoV-HKU1 in Korea, a sensitive, specific, and quantitative real-time polymerase
      chain reaction (PCR) assay was developed and analyzed the sequences of HCoV-HKU1
      isolated in Korea. A total of 1,985 respiratory specimens taken from patients
      with acute respiratory illness were tested for HCoV-HKU1 from January 2007 to May
      2008. The major clinical symptoms associated with HCoV-HKU1 infection were
      examined statistically and sequence variations of the RNA-dependent RNA
      polymerase (RdRp), spike, and nucleocapsid genes were also analyzed. Fifty cases
      (2.5%) HCoV-HKU1 were identified by real-time PCR and viral loads ranged from 6.7
      * 10(4) to 1.6 * 10(9)  copies/ml. The clinical symptoms of HCoV-HKU1 infection
      included rhinorrhea (72%), cough (64%), nasal congestion (56%), fever (32%),
      sputum (30%), sore throat (18%), chills (16%), postnasal discharge (14%), and
      tonsillar hypertrophy (10%). There was a seasonal distribution of HCoV-HKU1
      infection, peaking in winter and spring. Both genotypes A and B were detected but
      no recombination between them was found. This is the first report on the
      identification and genotyping of HCoV-HKU1 as a causative agent of acute
      respiratory illness in Korea. The data suggest that at least two genotypes, A and
      B, of HCoV-HKU1 with scattered silent mutations were circulating in Korea from
      2007 to 2008.

PMID- 23161447
TI  - Differential roles for Nr4a1 and Nr4a2 in object location vs. object recognition
      long-term memory.
AB  - Nr4a1 and Nr4a2 are transcription factors and immediate early genes belonging to
      the nuclear receptor Nr4a family. In this study, we examine their role in long
      term memory formation for object location and object recognition. Using siRNA to
      block expression of either Nr4a1 or Nr4a2, we found that Nr4a2 is necessary for
      both long-term memory for object location and object recognition. In contrast,
      Nr4a1 appears to be necessary only for object location. Indeed, their roles in
      these different types of long-term memory may be dependent on their expression in
      the brain, as NR4A2 was found to be expressed in hippocampal neurons (associated
      with object location memory) as well as in the insular and perirhinal cortex
      (associated with object recognition memory), whereas NR4A1 showed minimal
      neuronal expression in these cortical areas. These results begin to elucidate how
      NR4A1 and NR4A2 differentially contribute to object location versus object
      recognition memory.

PMID- 23161448
TI  - Latent inhibition in an insect: the role of aminergic signaling.
AB  - Latent inhibition (LI) is a decrement in learning performance that results from
      the nonreinforced pre-exposure of the to-be-conditioned stimulus, in both
      vertebrates and invertebrates. In vertebrates, LI development involves dopamine
      and serotonin; in invertebrates there is yet no information. We studied
      differential olfactory conditioning of the proboscis extension response in the
      honeybee Apis mellifera, and we compared LI in individuals treated with
      antagonists of biogenic amines (dopamine, octopamine, and serotonin). An
      antagonist of octopamine receptors and two antagonists of serotonin receptors
      showed LI disruption. We thus provide evidence that serotonin would participate
      in the regulation of LI in honeybees.

PMID- 23161445
TI  - Inflammation and colorectal cancer: colitis-associated neoplasia.
AB  - Connection between inflammation and cancer is a rapidly developing field.
      Epidemiological data suggests that inflammation along with distinct arms of host
      immune system plays a very important role in the development and progression of
      many different cancers. Inflammatory bowel disease (IBD) is an important risk
      factor for the development of colon cancer, namely, colitis-associated cancer
      (CAC). The molecular mechanisms by which inflammation promotes cancer development
      are still being uncovered and may differ between CAC and other forms of
      colorectal cancer. Recent work has shed light on the role of distinct immune
      cells, cytokines, and other immune mediators in virtually all of the steps of
      colonic tumorigenesis, including tumor initiation and promotion as well as
      progression and metastasis. The close proximity of colonic tumors to the myriad
      of intestinal microbes, as well as instrumental role of microbiota in IBD,
      introduces microbes as new players capable of triggering inflammation and
      possibly promoting tumorigenesis. Various mechanisms of CAC tumorigenesis as well
      as new possible hints for the future approaches for prevention and therapy are
      discussed in this review.

PMID- 23161449
TI  - Ontogeny of contextual fear memory formation, specificity, and persistence in
      mice.
AB  - Pinpointing the precise age when young animals begin to form memories of aversive
      events is valuable for understanding the onset of anxiety and mood disorders and
      for detecting early cognitive impairment in models of childhood-onset disorders.
      Although these disorders are most commonly modeled in mice, we know little
      regarding the development of learning and memory in this species because most
      previous studies have been restricted to rats. Therefore, in the present study,
      we constructed an ontogenetic timeline of contextual fear memory ranging from
      infancy to adulthood in mice. We found that the ability of mice to form long-term
      context-shock associations emerged ~13-14 d of age, which is several days earlier
      than previously reported for rats. Although the ability to form contextual fear
      memories remained stable from infancy into adulthood, infant mice had shorter
      lasting memories than adolescent and adult mice. Furthermore, we found that mice
      subjected to fetal alcohol exposure showed a delay in the developmental emergence
      of contextual fear memory, illustrating the utility of this ontogenetic approach
      in detecting developmental delays in cognitive function stemming from maladaptive
      early life experience.

PMID- 23161451
TI  - Probiotics in the intestinal tract of juvenile whiteleg shrimp Litopenaeus
      vannamei: modulation of the bacterial community.
AB  - Molecular analysis of the 16S rDNA of the intestinal microbiota of whiteleg
      shrimp Litopenaeus vannamei was examined to investigate the effect of a Bacillus
      mix (Bacillus endophyticus YC3-b, Bacillus endophyticus C2-2, Bacillus
      tequilensisYC5-2) and the commercial probiotic (Alibio((r))) on intestinal
      bacterial communities and resistance to Vibrio infection. PCR and single strain
      conformation polymorphism (SSCP) analyses were then performed on DNA extracted
      directly from guts. Injection of shrimp with V. parahaemolyticus at 2.5 * 10(5)
      CFU g(-1) per shrimp followed 168 h after inoculation with Bacillus mix or the
      Alibio probiotic or the positive control. Diversity analyses showed that the
      bacterial community resulting from the Bacillus mix had the highest diversity and
      evenness and the bacterial community of the control had the lowest diversity. The
      bacterial community treated with probiotics mainly consisted of alpha- and gamma
      proteobacteria, fusobacteria, sphingobacteria, and flavobacteria, while the
      control mainly consisted of alpha-proteobacteria and flavobacteria. Differences
      were grouped using principal component analyses of PCR-SSCP of the microbiota,
      according to the time of inoculation. In Vibrio parahaemolyticus-infected shrimp,
      the Bacillus mix (~33 %) induced a significant increase in survival compared to
      Alibio (~21 %) and the control (~9 %). We conclude that administration of the
      Bacillus mix induced modulation of the intestinal microbiota of L. vannamei and
      increased its resistance to V. parahaemolyticus.

PMID- 23161452
TI  - Complementary screening, identification and application of a novel class II 5
      enopyruvylshikimate-3-phosphate synthase from Bacillus cereus.
AB  - A novel aroA gene encoding 5-enolpyruvylshikimate-3-phosphate synthase from
      Bacillus cereus was identified and overexpressed by genomic library construction
      and complementary screening. The enzyme was then purified to homogeneity. We also
      transformed the aroA ( B. cereus ) gene into Arabidopsis thaliana by a floral dip
      method, and demonstrated that transgenic A. thaliana plants exhibited significant
      glyphosate resistance compared with the wild type. These results strongly
      suggested that the strategy was highly efficient and advantageous for rapidly
      cloning aroA genes from microorganisms in natural environments.

PMID- 23161453
TI  - Estimation of covariate effects with current status data and differential
      mortality.
AB  - The assessment of the impact that socioeconomic determinants have on the
      prevalence of certain chronic conditions reported by respondents in population
      surveys must confront two problems. First, the self-reports could be in error
      (false positives and false negatives). Second, those reporting are a selected
      sample of those who ever experience the problem, and this selection is heavily
      influenced by excess mortality attributable to the condition being reported. In
      this article, we use a combination of empirical data and microsimulation to (a)
      assess the magnitude of the bias attributable to the selection problem, and (b)
      suggest an adjustment procedure that corrects for this bias. We find that the
      proposed adjustment procedure considerably reduces the bias arising from
      differential mortality.

PMID- 23161454
TI  - Nontraditional families and childhood progress through school: a comment on
      Rosenfeld.
AB  - We reexamine Rosenfeld's (2010) study on the association between child outcomes
      and same-sex family structure. Using the same data set, we replicate and
      generalize Rosenfeld's findings and show that the implications of his study are
      different when using either alternative comparison groups or alternative sample
      restrictions. Compared with traditional married households, we find that children
      being raised by same-sex couples are 35 % less likely to make normal progress
      through school; this difference is statistically significant at the 1 % level.

PMID- 23161455
TI  - Nontraditional families and childhood progress through school.
AB  - Allen et al.'s results depend on their inclusion of children whose family at the
      time of their grade retention is unknown, plus adopted and foster children whose
      selection process into families is unknown. Children whose family has been
      through upheavals or transitions are less likely to make good progress in school
      than children from stable families. Children raised by stable same-sex couples do
      remarkably well in school.

PMID- 23161458
TI  - Sleep, behavioral rhythms, and neurological disease.

PMID- 23161457
TI  - MBNL1 gene variants as modifiers of disease severity in myotonic dystrophy type
      1.
AB  - Myotonic dystrophy type 1 (DM1) is a multisystemic autosomal dominant disorder
      characterized by a highly variable phenotype and caused by an unstable CTG repeat
      expansion in the 3' untranslated region of the dystrophia myotonica protein
      kinase (DMPK) gene. Longer CTG repeat expansions often correlate with an
      anticipated age at onset and CTG repeat number may account for 45-60 % of the
      variance in disease severity. In order to search for candidate genes that could
      act as modifiers of disease severity, we studied the association between
      Muscleblind-like protein-1 (MBNL1) gene polymorphisms and the DM1 phenotype. In a
      group of 301 patients diagnosed with DM1 based on clinical symptoms, diagnosis
      was confirmed by molecular analysis of the DMPK gene. Patients were divided into
      four subtypes. The first subtype corresponded to asymptomatic patients or those
      with a mild phenotype, the second included those with a classic phenotype, the
      third concerned childhood onset, and the fourth corresponded to the congenital
      form of DM1. Three SNPs located in the MBNL1 gene promoter, rs323622, rs17283597,
      and rs17433672, were studied. Case-control analysis revealed that allele
      frequencies for the latter two were significantly associated with DM1 (p = 0.037
      and p = 0.020). Multivariate linear regression analysis using phenotype as the
      dependent variable demonstrated that the TT genotype of the third SNP, rs323622,
      was associated with a more severe phenotype (p = 0.0034) and accounted for 1.88 %
      of the variance in disease severity. We report the association of several genetic
      variants of the MBNL1 gene with DM1 or with the severity of the disease.

PMID- 23161460
TI  - Disease reactivation after fingolimod discontinuation in two multiple sclerosis
      patients.

PMID- 23161461
TI  - Isolated spasticity in sporadic Creutzfeldt-Jakob disease.

PMID- 23161462
TI  - A nurse-led self-management intervention for people who attend emergency
      departments with epilepsy: the patients' view.
AB  - Some people with chronic epilepsy (PWE) make clinically unnecessary, and
      potentially avoidable, visits to hospital emergency departments. Whilst
      expensive, it is not known how to reduce them. We recently conducted the first
      trial of an epilepsy-nurse specialist intervention which aimed to optimise self
      management skills in PWE attending emergency departments and advise them on
      appropriate emergency services use. Based on in-depth semi-structured interviews,
      we here report the perceived support needs of patients who have attended a
      emergency department for epilepsy and the benefits of the intervention which they
      identified. Nested qualitative study. After receiving the intervention, 20
      participants were invited to interview. They described their experience of the
      intervention, to what extent they valued it and its benefits and limitations.
      Interviews were audio-recorded, transcribed and thematically analysed. Most
      valued the additional support. Those who previously used emergency departments
      most perceived greatest benefit. Participants felt it redressed limitations to
      usual care, including providing information about living with epilepsy, and an
      opportunity to discuss feelings about epilepsy. Perceived benefits included
      improvements in emotional well-being, confidence dealing with seizures and
      medication adherence. The intervention was acceptable to patients. People with
      epilepsy who had attended a emergency department on more than one occasion
      perceived most benefit. This suggests they want additional care. Some perceived
      benefits in domains possibly causally related to emergency department use. This
      suggests the intervention, with optimisation, may have the components to reduce
      emergency department visits. Our results provide insights into how to support PWE
      who attend emergency departments and how needs differ amongst this group.

PMID- 23161456
TI  - Dysexecutive and amnesic AD subtypes defined by single indicator and modern
      psychometric approaches: relationships with SNPs in ADNI.
AB  - Previous investigators have suggested the existence of distinct cognitive
      phenotypes of Alzheimer's disease (AD): a dysexecutive subgroup with executive
      functioning worse than memory and an amnesic subgroup with memory worse than
      executive functioning. We evaluated data from the AD Neuroimaging Initiative. We
      assigned people with AD to dysexecutive and amnesic subgroups using single
      indicators, and analogously using the ADNI-Mem and ADNI-EF composite scores
      developed using modern psychometric approaches. We evaluated associations between
      subgroup membership, APOE genotype, and single nucleotide polymorphisms (SNPs)
      are associated with AD, and brain vascular disease defined as white matter
      hyperintensities (WMH) and MRI-identified infarcts. We hypothesized that APOE
      epsilon4 and alleles associated with higher risk for AD would predict amnesic
      subgroup membership; alleles associated with higher WMH or infarct burden would
      predict dysexecutive subgroup membership. Classification agreement between the
      two approaches was only fair (kappa = 0.23). There was no relationship between
      APOE alleles and the dysexecutive or amnesic phenotypes defined by either
      categorization approach. There were 58 AD-related and 25 WMH- or infarct-related
      SNPs for which odds ratios were > 1.5 or < 0.67 for dysexecutive vs. amnesic
      subgroup defined by either categorization approach. Higher proportions of SNPs
      had odds ratios in the hypothesized direction for the subgroups defined by the
      modern psychometric approach for AD-related (58 % vs. 38 %, p-value < 0.001) and
      brain vascular disease-related SNPs (48 vs. 32 %, p-value = 0.01). Genetic
      variation may underlie differential performance in memory and executive
      functioning among people with AD. Modern psychometric composite scores produced
      group assignments with more SNP associations in the hypothesized direction.

PMID- 23161463
TI  - Recent advances in clinical neurogenetics.
AB  - Herein, I review the main papers in neurogenetic research published in the
      Journal of Neurology over the last year. 

PMID- 23161464
TI  - Neuroproteomics approach and neurosystems biology analysis: ROCK inhibitors as
      promising therapeutic targets in neurodegeneration and neurotrauma.
AB  - Several common degenerative mechanisms and mediators underlying the neuronal
      injury pathways characterize several neurodegenerative diseases including
      Alzheimer's, Parkinson's, and Huntington's disease, as well as brain neurotrauma.
      Such common ground invites the emergence of new approaches and tools to study the
      altered pathways involved in neural injury alongside with neuritogenesis, an
      intricate process that commences with neuronal differentiation. Achieving a
      greater understanding of the impaired pathways of neuritogenesis would
      significantly help in uncovering detailed mechanisms of axonal regeneration.
      Among the several agents involved in neuritogenesis are the Rho and Rho kinases
      (ROCKs), which constitute key integral points in the Rho/ROCK pathway that is
      known to be disrupted in multiple neuropathologies such as spinal cord injury,
      traumatic brain injury, and Alzheimer's disease. This in turn renders ROCK
      inhibition as a promising candidate for therapeutic targets for treatment of
      neurodegenerative diseases. Among the novel tools to investigate the mechanisms
      involved in a specific disorder is the use of neuroproteomics/systems biology
      approach, a growing subfield of bioinformatics aiming to study and establishing a
      global assessment of the entire neuronal proteome, addressing the dynamic protein
      changes and interactions. This review aims to examine recent updates regarding
      how neuroproteomics aids in the understanding of molecular mechanisms of
      activation and inhibition in the area of neurogenesis and how Rho/ROCK
      pathway/ROCK inhibitors, primarily Y-27632 and Fasudil compounds, are applied in
      biological settings, promoting neuronal survival and neuroprotection that has
      direct future implications in neurotrauma.

PMID- 23161465
TI  - Five non-synonymous SNPs in the gene encoding human deoxyribonuclease I-like 2
      implicated in terminal differentiation of keratinocytes reduce or abolish its
      activity.
AB  - Several non-synonymous SNPs in the human deoxyribonuclease I-like 2 (DNase 1L2)
      gene responsible for DNA degradation during terminal differentiation of epidermal
      keratinocytes have been identified. However, only limited population data are
      available, and furthermore the effect of these SNPs on the DNase 1L2 activity
      remains unknown. Genotyping of all of the 17 SNPs was performed using the PCR
      RFLP method in three ethnic groups including 14 different populations. A series
      of amino acid-substituted DNase 1L2 corresponding to each SNP was expressed, and
      its activity was measured. All of the six non-synonymous SNPs exhibited a mono
      allelic distribution, whereas the distribution of some SNPs other than exonic
      ones was ethnicity-dependent. Each of the minor alleles in SNPs, p.Ala20Asp,
      p.Val104Leu, p.Asp197Ala, p.Glu274Lys and p.Asp287Asn, among the non-synonymous
      SNPs produced low or no activity-harbouring DNase 1L2. DNase 1L2 is well
      conserved, retaining full levels of enzymatic activity, with regard to these
      exonic SNPs in human populations. It seems plausible to assume that these SNPs
      affecting the activity may be one of the factors responsible for a genetic pre
      disposition for failure of differentiation-associated cell death in various
      keratinocyte lineages, thereby leading to the development of parakeratosis. Our
      results may have clinical implications in relation to the pathogenesis of
      parakeratosis.

PMID- 23161466
TI  - [Results of a structural diagnosis of patients with chronic dyspnoea recruited
      from two cardiological practices].
AB  - While well validated algorithms exist for the diagnosis of patients with acute
      dyspnoea, such generally valid procedural instructions are lacking for patients
      with chronic dyspnoea. The diagnostic approach presented here is based on
      investigations of 246 patients with chronic dyspnoea recruited from two
      cardiological practices using a self-developed multi-level procedure. Besides
      anamnestic and clinical examinations, different diagnostic procedures, available
      in the ambulant range, are included. The results suggest that in over 50 % of the
      cases the cause of chronic dyspnoea can be determined from anamnestic and
      clinical examinations as well as from electrocardiogram and echocardiography.
      Additional inclusion of lung function and capillary blood gas analysis permitted
      a sufficient clarification in over 80 % of the cases. In a further step,
      cardiopulmonary exercise testing clarified the reasons for chronic dyspnoea in
      approximately 10 % of the remaining patients. Threshold values of lung function
      parameters as used for the differentiation of acute dyspnoea, do not seem
      suitable for the diagnosis of patients with chronic dyspnoea. By means of a
      simple step-wise diagnostic algorithm, applicable under ambulant conditions, the
      cause of chronic dyspnoea could sufficiently be clarified in more than 95 % of
      the cases.

PMID- 23161467
TI  - Proteomic analysis and brain-specific systems biology in a rodent model of
      penetrating ballistic-like brain injury.
AB  - Proteomics and systems biology have significantly contributed to biomarker
      discovery in the field of brain injury. This study utilized 2D-DIGE-PMF-MS as a
      preliminary screen to detect biomarkers in a rat model of penetrating ballistic
      like brain injury (PBBI). Brain-specific systems biology analysis of brain tissue
      identified 386 proteins having a fold change of more than 2, of which 321
      proteins were increased and 65 were decreased 24 h after PBBI compared to sham
      controls. The majority of upregulated proteins were cytoskeletal (10.5%), nucleic
      acid binding (9.3%), or kinases (8.9%). Most proteins were involved in protein
      metabolism (22.7%), signal transduction (20.4%), and development (9.6%). Pathway
      analysis indicated that these proteins were involved in neurite outgrowth and
      cell differentiation. Semiquantitative Western blotting of 6, 24, 48, and 72 h
      after PBBI indicated ubiquitin carboxyl-terminal hydrolase isozyme L1 (a proposed
      traumatic brain injury biomarker in human clinical trials), tyrosine hydroxylase,
      and syntaxin-6 were found to be consistently elevated in brain tissue and
      cerebral spinal fluid after PBBI compared to sham controls. Combining proteomics
      and brain-specific systems biology can define underlying mechanisms of traumatic
      brain injury and provide valuable information in biomarker discovery that, in
      turn, may lead to novel therapeutic targets.

PMID- 23161468
TI  - Mucosal melanoma of the head and neck: 32-year experience in a tertiary referral
      hospital.
AB  - INTRODUCTION: Primary mucosal melanomas of the head and neck (HNMM), albeit being
      rare, are rapidly lethal. Here we report the experience of patients with HNMM
      treated in our institution over a 32-year period. OBJECTIVES/HYPOTHESIS: We aim
      to review our experience in managing HNMM patients over a 32-year period. STUDY
      DESIGN: Retrospective study. METHODS: Thirty-five patients diagnosed with HNMM
      from 1978 to 2009 were retrospectively reviewed, with an emphasis on predictors
      on survival outcome. RESULTS: Twenty-four patients received curative resection, 6
      of them followed by adjuvant radiotherapy. Neck dissections were performed in 8
      patients. Four patients received radiotherapy as primary treatment. Seven
      patients were treated conservatively. The overall mean and median survivals were
      50 and 26 months, respectively. The median survival of stage I, II, and III
      diseases in our group of patients were 39, 10, and 16 months, respectively. The 1
      year and 5-year overall survival rates were 65.7% and 22.9%, respectively. Age
      above 60 (p = 0.007), nodal involvement (p = 0.047;) and stage at presentation (p
      = 0.046) were shown to be associated with worse overall survival. Sites of tumour
      did not seem to impact on survival. On multivariate analysis, only age (below or
      above 60) was found to be statistically significant [RR 4.79 (1.65-13.9), p =
      0.004]. CONCLUSIONS: Oral cavity melanomas are more likely to have nodal
      involvement at presentation. Prognosis of HNMM remains grave. Current evidence
      still supports surgery as the best chance of cure. Role of adjuvant radiotherapy
      is controversial and does not appear to improve overall survival. Similarly, role
      of neck dissection is ill-defined.

PMID- 23161470
TI  - Two-stage metal-catalyst-free growth of high-quality polycrystalline graphene
      films on silicon nitride substrates.
AB  - By using two-stage, metal-catalyst-free chemical vapor deposition (CVD), it is
      demonstrated that high-quality polycrystalline graphene films can directly grow
      on silicon nitride substrates. The carrier mobility can reach about 1500 cm(2) 
      V(-1)  s(-1) , which is about three times the value of those grown on SiO(2) /Si
      substrates, and also is better than some examples of metal-catalyzed graphene,
      reflecting the good quality of the graphene lattice.

PMID- 23161469
TI  - HCV-infected hepatocytes drive CD4+ CD25+ Foxp3+ regulatory T-cell development
      through the Tim-3/Gal-9 pathway.
AB  - HCV is remarkable at disrupting human immunity to establish chronic infection.
      The accumulation of Treg cells at the site of infection and upregulation of
      inhibitory signaling pathways (such as T-cell Ig and mucin domain protein-3 (Tim
      3) and galectin-9 (Gal-9)) play pivotal roles in suppressing antiviral effector T
      (Teff) cells that are essential for viral clearance. While Tim-3/Gal-9
      interactions have been shown to negatively regulate Teff cells, their role in
      regulating Treg cells is poorly understood. To explore how Tim-3/Gal-9
      interactions regulate HCV-mediated Treg-cell development, here we provide pilot
      data showing that HCV-infected human hepatocytes express higher levels of Gal-9
      and TGF-beta, and upregulate Tim-3 expression and regulatory cytokines TGF
      beta/IL-10 in co-cultured human CD4(+)  T cells, driving conventional CD4(+)  T
      cells into CD25(+) Foxp3(+)  Treg cells. Additionally, recombinant Gal-9 protein
      can transform TCR-activated CD4(+)  T cells into Foxp3(+)  Treg cells in a dose
      dependent manner. Importantly, blocking Tim-3/Gal-9 ligations abrogates HCV
      mediated Treg-cell induction by HCV-infected hepatocytes, suggesting that Tim
      3/Gal-9 interactions may regulate human Foxp3(+)  Treg-cell development and
      function during HCV infection.

PMID- 23161471
TI  - Prion protein as a mediator of neurocardiosympathetic interactions.
AB  - A proteomic approach to study cardiovascular disease includes the examination of
      proteins associated with risk factors such as left ventricular hypertrophy (LVH).
      PrP(C) is a host-coded membrane-bound glycoprotein found in most cell types,
      including myocardium, and whose physiological function is uncertain. We have
      taken a selective proteomic approach and performed mechanistic studies to
      determine whether PrP(C) levels are related to left ventricular (LV) structure or
      function. Echocardiograms were performed at baseline in 65 mice comprising three
      strains of the same C57Bl/6J * 129SV genetic background but expressing different
      levels of PrP(C) (wild-type mice (WT), PrP(-/-) , and PrP(C) over-expressing
      transgenic mice (tga20)). There were no significant differences in LV mass or LV
      ejection fraction between the three groups. Either normal saline (n = 60) or
      isoproterenol (n = 55) was then administered intraperitoneally (50 mg/kg/day) for
      5 days/wk for two consecutive weeks to induce LVH. Body weight decreased
      significantly in the PrP(-/-) group (18%). On multivariate analysis, higher LV
      mass index posttreatment was independently associated with the tga20 group
      (versus PrP(-/-) versus WT, p = 0.002) after adjusting for treatment
      (isoproterenol versus saline), and weight change (r(2) = 0.13 for model, p =
      0.016). Therefore, PrP(C) appears unrelated to LV mass and function in the basal
      state. Isoproterenol causes transient enhancement of PrP(C) expression in WT mice
      and a more pronounced increase in tga20 mice at 2 h posttreatment. Overexpression
      of PrP(C) in the tga20 group may be associated with higher LV mass after a 2 wk
      regimen of isoproterenol.

PMID- 23161472
TI  - Daily spousal influence on physical activity in knee osteoarthritis.
AB  - BACKGROUND: Physical activity is critical for the management of knee
      osteoarthritis, and the spouse may play a role in encouraging or discouraging
      physical activity. PURPOSE: The purpose of this study was to examine four types
      of spousal influence-spouses' daily activity, autonomy support, pressure, and
      persuasion-on the daily physical activity of adults living with knee
      osteoarthritis. METHODS: A total of 141 couples reported their daily experiences
      for 22 days using a handheld computer and wore an accelerometer to measure
      moderate activity and steps. RESULTS: Spouses' autonomy support for patient
      physical activity, as well as their own level of activity, was concurrently
      associated with patients' greater daily moderate activity and steps. In addition,
      on days when male patients perceived that spouses exerted more pressure to be
      active, they spent less time in moderate activity. CONCLUSIONS: Couple-oriented
      interventions for knee osteoarthritis should target physical activity in both
      partners and spousal strategies for helping patients stay active.

PMID- 23161474
TI  - Surface growth kinematics via local curve evolution.
AB  - A mathematical framework is developed to model the kinematics of surface growth
      for objects that can be generated by evolving a curve in space, such as seashells
      and horns. Growth is dictated by a growth velocity vector field defined at every
      point on a generating curve. A local orthonormal basis is attached to each point
      of the generating curve and the velocity field is given in terms of the local
      coordinate directions, leading to a fully local and elegant mathematical
      structure. Several examples of increasing complexity are provided, and we
      demonstrate how biologically relevant structures such as logarithmic shells and
      horns emerge as analytical solutions of the kinematics equations with a small
      number of parameters that can be linked to the underlying growth process. Direct
      access to cell tracks and local orientation enables for connections to be made to
      the underlying growth process. 

PMID- 23161473
TI  - A network with tunable clustering, degree correlation and degree distribution,
      and an epidemic thereon.
AB  - A random network model which allows for tunable, quite general forms of
      clustering, degree correlation and degree distribution is defined. The model is
      an extension of the configuration model, in which stubs (half-edges) are paired
      to form a network. Clustering is obtained by forming small completely connected
      subgroups, and positive (negative) degree correlation is obtained by connecting a
      fraction of the stubs with stubs of similar (dissimilar) degree. An SIR
      (Susceptible --> Infective --> Recovered) epidemic model is defined on this
      network. Asymptotic properties of both the network and the epidemic, as the
      population size tends to infinity, are derived: the degree distribution, degree
      correlation and clustering coefficient, as well as a reproduction number R(*),
      the probability of a major outbreak and the relative size of such an outbreak.
      The theory is illustrated by Monte Carlo simulations and numerical examples. The
      main findings are that (1) clustering tends to decrease the spread of disease,
      (2) the effect of degree correlation is appreciably greater when the disease is
      close to threshold than when it is well above threshold and (3) disease spread
      broadly increases with degree correlation rho when R(*) is just above its
      threshold value of one and decreases with rho when R(*) is well above one.

PMID- 23161475
TI  - MRT letter: localization of endogenous hydrogen peroxide by modified processes of
      sample preparation for transmission electron microscope in Escherichia coli.
AB  - The bacterial endogenous hydrogen peroxide (H(2)O(2)) was detected cytochemically
      by its reaction with cerium chloride (CeCl(3)) to produce electron-dense deposits
      of cerium perhydroxides. The sequence of fixation and CeCl(3) staining of
      H(2)O(2) in the processing of transmission electron microscope (TEM) sample
      preparation is crucial to the localization of endogenous H(2)O(2) in Escherichia
      coli. In this study, results confirmed that the process that fixation
      simultaneously with CeCl(3) staining provided optimum effects for H(2)O(2)
      localization in E. coli. The modified process of TEM provides very efficient
      protection for H(2)O(2) localization and more accurate quantization for the
      H(2)O(2) accumulation in bacterial cells.

PMID- 23161476
TI  - High prevalence of undiagnosed obstructive sleep apnoea in the general population
      and methods for screening for representative controls.
AB  - PURPOSE: Undiagnosed obstructive sleep apnoea (OSA) in the community makes
      comparisons of OSA subjects with control samples from the general population
      problematic. This study aims to estimate undiagnosed moderate to severe OSA in a
      general population sample and to determine the capacity of questions from the
      Berlin questionnaire (BQ) to identify subjects without diagnosed OSA of this
      severity. METHODS: Using a general population sample (n = 793) with no history of
      OSA, case and control status for moderate-severe OSA was determined by home-based
      nasal flow and oximetry-derived apnoea-hypopnoea index using a cut-off value of
      >= 15 events/h to define cases. The diagnostic accuracy of the complete BQ and
      its component questions in identifying cases was assessed by calculating
      sensitivity, specificity, positive and negative predictive values, positive and
      negative likelihood ratios and post-test probabilities. RESULTS: The age
      standardised prevalence estimate of moderate-severe OSA was 9.1 % (12.4 % in men,
      5.7 % in women). Sensitivity of the BQ in this population was 54 %, and
      specificity, 70 %. A combination of questions regarding snoring frequency and
      hypertension provided maximal post-test probability of OSA and greatest post
      screen sample size. CONCLUSIONS: Undiagnosed OSA is highly prevalent in the
      Western Australian general population. While the complete BQ is a sub-optimal
      screening instrument for the general population, snoring frequency or
      hypertension can be used to screen out moderate-severe OSA from general
      population samples with limited reduction in sample size. As there are few
      general population samples available for epidemiological or genetic studies of
      OSA and its associated phenotypes, these results may usefully inform future case
      control studies.

PMID- 23161477
TI  - Acute sleep deprivation in healthy adults is associated with a reduction in left
      atrial early diastolic strain rate.
AB  - BACKGROUND: Sleep deprivation (SD) is known to be associated with adverse
      cardiovascular events. Strain and strain rate measure the local deformation of
      the myocardium and have been used to evaluate atrial phasic function in various
      disease states. The aim of the study was to investigate whether strain rate
      imaging enables the identification of left atrial dysfunction in otherwise
      healthy young adults with acute SD which has not been studied previously.
      METHODS: Adequate echocardiographic images of 27 healthy volunteers were obtained
      both after a night with regular sleep and after a night with SD. Tissue Doppler
      derived strain and strain rate were measured from the apical four- and two
      chamber views of the left atrium, and global values were calculated as the mean
      of all segments. Measurements included peak systolic strain, systolic strain rate
      (S-Sr), early diastolic (E-Sr) and late diastolic (A-Sr) strain rate. Phasic left
      atrial (LA) volumes and fractions were also calculated. RESULTS: There was no
      significant difference in the traditional parameters of atrial function and LA
      volumes. Subjects had similar S-Sr, A-Sr and global atrial strain values after
      the night of sleep debt when compared after regular sleep, whereas they had
      significantly reduced E-Sr values (mean (SD) 3.2 (0.7) s(-1) vs 3.7 (0.6) s(-1),
      p < 0.001). Moreover, global E-Sr showed a significant correlation with sleep
      time (r = 0.554, p < 0.001). CONCLUSION: Acute SD in healthy adults is associated
      with a reduction in LA early diastolic strain rate in the absence of geometric
      alterations or functional impairment of the left atrium, raising the possibility
      that chronic SD may more profoundly affect LA function and thereby promote the
      occurrence of atrial fibrillation.

PMID- 23161478
TI  - Native agarose gel electrophoresis and electroelution: A fast and cost-effective
      method to separate the small and large hepatitis B capsids.
AB  - Hepatitis B core antigen (HBcAg) expressed in Escherichia coli is able to self
      assemble into large and small capsids comprising 240 (triangulation number T = 4)
      and 180 (triangulation number T = 3) subunits, respectively. Conventionally,
      sucrose density gradient ultracentrifugation and SEC have been used to separate
      these capsids. However, good separation of the large and small particles with
      these methods is never achieved. In the present study, we employed a simple,
      fast, and cost-effective method to separate the T = 3 and T = 4 HBcAg capsids by
      using native agarose gel electrophoresis followed by an electroelution method
      (NAGE-EE). This is a direct, fast, and economic method for isolating the large
      and small HBcAg particles homogenously based on the hydrodynamic radius of the
      spherical particles. Dynamic light scattering analysis demonstrated that the T =
      3 and T = 4 HBcAg capsids prepared using the NAGE-EE method are monodisperse with
      polydispersity values of ~15% and ~13%, respectively. ELISA proved that the
      antigenicity of the capsids was not affected in the purification process.
      Overall, NAGE-EE produced T = 3 and T = 4 capsids with a purity above 90%, and
      the recovery was 34% and 50%, respectively (total recovery of HBcAg is ~84%), and
      the operation time is 15 and 4 times lesser than that of the sucrose density
      gradient ultracentrifugation and SEC, respectively.

PMID- 23161479
TI  - The genetics of Behcet's disease in a Chinese population.
AB  - Behcet's disease is defined as a multisystemic inflammatory disease. Although the
      precise pathogenesis and etiology is still a mystery, accumulating evidence shows
      that genetic variants of immune-related genes have a profound influence on the
      development of Behcet's disease. To explore the genetic factors for Behcet's
      disease, our group investigated the association of Behcet's disease with multiple
      immune response genes and has identified multiple Behcet's disease-related
      immunoregulatory pathways in the Chinese Han population. A large number of gene
      polymorphisms were studied including STAT4, IL23R, CD40, CCR1/CCR3, STAT3, OPN,
      IL17, JAK2, MCP-1, CTLA4, PD-1, PD-L1, PD-L2, TGRBR3, CCR6, PTPN22, FCRL3, IRF5,
      SUMO4 and UBAC2. Significant associations were found between Behcet's disease and
      STAT4, IL23R, CD40, CCR1/CCR3, STAT3, MCP-1, TGFBR3, FCRL3, SUMO4, UBAC2. These
      genetic predisposition studies support an important role for both lymphocyte
      differentiation as well as ubiquitination pathways. These findings are helpful in
      elucidating the pathogenesis of Behcet's disease and hopefully will allow the
      development of novel treatment regimes.

PMID- 23161480
TI  - Newly designed bioabsorbable substitute for the treatment of diaphragmatic
      defects.
AB  - PURPOSE: Earlier studies have investigated the suitability of various materials
      and autologous grafts for the repair of diaphragmatic defects. Our group
      investigated the feasibility of using an artificial diaphragm (AD) to repair wide
      diaphragmatic defects. METHODS: Twelve pigs were laparotomized and, in each pig,
      a defect was fashioned by resecting a round 8-cm diameter hole in the left
      diaphragm. Next, the defect was repaired by implanting an AD. The animals were
      relaparotomized 8 or 24 weeks after implantation for gross, histological and
      radiological observation of the implanted sites. RESULTS: All recipient animals
      survived until killing for evaluation. Chest X-ray examinations showed no
      differences between the preoperative diaphragms and the grafted diaphragms at 8
      and 24 weeks after implantation. At 8 weeks after implantation, the implanted
      sites exhibited fibrous adhesions to the liver and lungs without deformities or
      penetrations. Parts of the surface tissue at the graft sites had a varnished
      appearance similar to those of the native diaphragm. Histology performed at 8
      weeks detected no trace of the ADs in the graft sites; however, numerous
      inflammatory cells and profuse fibrous connective tissue were observed. At 24
      weeks after implantation, no differences were found in the thorax between the
      areas with the grafts and the unaffected areas. Histology of the graft sites in
      the thorax confirmed growth of mesothelial cells similar to that observed in the
      native diaphragm. CONCLUSIONS: Artificial diaphragms can be a novel substitute
      for diaphragmatic repair.

PMID- 23161481
TI  - Successful n-butyl cyanoacrylate embolization of a spontaneous rupture of the
      internal mammary artery in a patient with myelodysplastic syndrome: report of a
      case.
AB  - Hemomediastinum and hemothorax due to spontaneous internal mammary artery (IMA)
      rupture is extremely rare, and can be a life-threatening condition. We herein
      present, to the best of our knowledge, the first case of spontaneous IMA rupture
      complicating myelodysplastic syndrome, and the first case that was successfully
      treated by emergency trans-arterial embolization using n-butyl cyanoacrylate. 

PMID- 23161482
TI  - Postpartum acute coronary syndrome due to intramural hematoma and coronary artery
      dissection.
AB  - A 38-year-old woman presented with acute coronary syndrome 9 days postpartum.
      Coronary catheterization showed an intramural hematoma of the left main artery
      (LM) and the left anterior descending artery (LAD). During angiography,
      dissection of the LM, with involvement of the LAD and circumflex artery occurred.
      The patient presented unstable hemodynamic status. After resuscitation, intra
      aortic balloon pump was inserted. The patient underwent two-vessel off-pump
      surgical revascularization. She was discharged 10 days later.

PMID- 23161483
TI  - Long-term population survey of the Sulawesi black macaques (Macaca nigra) at
      Tangkoko Nature Reserve, North Sulawesi, Indonesia.
AB  - The Sulawesi black macaque (Macaca nigra) population at Tangkoko Nature Reserve
      in North Sulawesi, Indonesia has been the focus of periodic study for over 30
      years. The population has shown considerable decline during much of that time.
      Here we present the results of a long-term population survey of the Tangkoko M.
      nigra, conducted over the past decade, to provide updated information and on
      going assessment of the population. Line-transect sampling was conducted annually
      from 1999 to 2002 and 2005 to 2011 along the same transect during a 2- to 3-week
      survey period. Although further decline in the population was observed at the
      outset of the survey, over the subsequent 12-year period we have seen stability
      in the population parameters with evidence of modest increases in both group and
      population density. During the 1999-2002 survey periods, there was a mean group
      density of 3.6 groups/km(2) and a mean population density of 39.8
      individuals/km(2) . During 2005-2011, mean group density increased to 3.8
      groups/km(2) and mean population density was 51.4 individuals/km(2) . The 2011
      survey data indicated an estimated group density of 4.3 groups/km(2) and a
      population density of 61.5 individuals/km(2) . Given that our transect was
      located in the core of the Tangkoko reserve, our density estimates should be
      limited to that area of the reserve. One explanation for the apparent
      stabilization of the population may be tied to the increasing and sustained
      number of training and research programs being conducted at the reserve. This
      collective effort by local and international groups may be helping to reduce
      illegal activity in the reserve (i.e., hunting and habitat destruction) and
      generate greater awareness of this critically endangered species. Without the
      continued vigilance afforded by the existing research and training programs and
      the support and involvement of the local people, the M. nigra at the Tangkoko
      Nature Reserve will likely face further decline.

PMID- 23161484
TI  - Toxicity of forest fire retardant chemicals to stream-type chinook salmon
      undergoing parr-smolt transformation.
AB  - Long-term fire retardants are used to prevent the spread of wildland fires. These
      products are normally applied by aircraft and are intended specifically for
      terrestrial application, but fire retardants have entered aquatic habitats by
      misapplication and/or accidental spills and have resulted in fish mortalities.
      The authors examined the toxicity of two fire retardant products, PHOS-CHEK 259F
      and LC-95A, to salmon undergoing parr-smolt transformation. Yearling stream-type
      chinook salmon at the smolt stage were exposed to eight concentrations of each
      retardant in freshwater and a no-PHOS-CHEK control for 96 h to determine acute
      toxicity. Concentrations of the products that caused 50% mortality were 140.5 and
      339.8 mg/L for 259F and LC-95A, respectively, and could occur during accidental
      drops into aquatic habitats. Damage to gill tissues seen in histopathological
      sections was attributed to fire retardant exposure. Un-ionized ammonia levels,
      from 259F, were sufficient to cause acute mortality; but additional factors,
      indicated by increased phagosome prevalence in the gills, might have contributed
      to mortality during LC-95A exposure. Seawater and disease challenges were
      performed to determine sublethal effects of product exposures on fish health.
      Although PHOS-CHEK exposure did not adversely affect chinook salmon's
      susceptibility to Listonella anguillarum, exposure did significantly reduce
      seawater survival. Reduced salmon survival resulting from prior fire retardant
      exposure during their transition from freshwater rearing environments to seawater
      may decrease the abundance of salmon populations.

PMID- 23161485
TI  - Pd-catalyzed C-H oxygenation with TFA/TFAA: expedient access to oxygen-containing
      heterocycles and late-stage drug modification.
AB  - Acid brings the oxygen: a general method for palladium-catalyzed C-H oxygenation
      has been developed for the facile synthesis of a wide range of functionalized
      phenols with readily available aryl ketones, benzoates, benzamides, acetanilides,
      and sulfonamides. A trifluoroacetic acid/trifluoroacetic acid anhydride solvent
      system serves as the oxygen source and is the critical factor for C-H activation.

PMID- 23161486
TI  - The anatomical relationship between the eustachian tube and petrous internal
      carotid artery.
AB  - OBJECTIVES/HYPOTHESIS: The aim of the present study was to investigate the
      relationship between the eustachian tube (ET) and petrous internal carotid artery
      (ICA) in whole-mount human temporal bone specimens. STUDY DESIGN: Descriptive
      study. METHODS: Histologically prepared serial sections of 10 adult temporal
      bones were included in the study. Five specific landmarks were selected to
      evaluate relationships between the petrous segment of the ICA and the ET. The
      selected distances were measured using computer software (Metamorph 7.5.2.0;
      Molecular Devices, LLC, Sunnyvale, CA). RESULTS: The ET and the ICA get close
      posteriorly, and the bony part of the ET and the ICA generally share the same
      wall. CONCLUSIONS: The junctional part of the ET may be a safe landmark to
      identify and protect the ICA during endoscopic endonasal surgery of the cranial
      base. Knowledge of the anatomical relationships of the ET and petrous part of the
      ICA, as well as their relationship with other surgical and radiological
      landmarks, would be useful to surgeons.

PMID- 23161487
TI  - Simulating realistic genomic data with rare variants.
AB  - Increasing evidence suggests that rare and generally deleterious genetic variants
      might have a strong impact on disease risks of not only Mendelian disease, but
      also many common diseases. However, identifying such rare variants remains
      challenging, and novel statistical methods and bioinformatic software must be
      developed. Hence, we have to extensively evaluate various methods under
      reasonable genetic models. Although there are abundant genomic data, they are not
      most helpful for the evaluation of the methods because the disease mechanism is
      unknown. Thus, it is imperative that we simulate genomic data that mimic the real
      data containing rare variants and that enable us to impose a known disease
      penetrance model. Although resampling simulation methods have shown their
      advantages in computational efficiency and in preserving important properties
      such as linkage disequilibrium (LD) and allele frequency, they still have
      limitations as we demonstrated. We propose an algorithm that combines a
      regression-based imputation with resampling to simulate genetic data with both
      rare and common variants. Logistic regression model was employed to fit the
      relationship between a rare variant and its nearby common variants in the 1000
      Genomes Project data and then applied to the real data to fill in one rare
      variant at a time using the fitted logistic model based on common variants.
      Individuals then were simulated using the real data with imputed rare variants.
      We compared our method with existing simulators and demonstrated that our method
      performed well in retaining the real sample properties, such as LD and minor
      allele frequency, qualitatively.

PMID- 23161488
TI  - Microchip CE-LIF method for the hydrolysis of L-glutamine by using L-asparaginase
      enzyme reactor based on gold nanoparticle.
AB  - L-Asparaginase (L-Asnase) can suppress the growth of malignant cells by rapid
      depletion of two essential amino acids, L-glutamine (L-Gln) and L-asparagine (L
      Asn). To study the cytotoxic effect and the secondary complications of L-Asnase
      in the treatment of acute lymphoblastic leukemia, the development of a novel
      enzyme reactor of L-Asnase for the hydrolysis of L-Gln, employing the enzyme-gold
      nanoparticle conjugates in capillary, was reported in this work. First, a
      microchip CE (MCE)-LIF was established for the separation of L-amino acids (L-Gln
      and L-glutamic acid) and studying the hydrolysis of L-Gln by using L-Asnase
      enzyme reactor. Then, using L-Gln as target analyte, the enzyme kinetics of L
      Asnase in free solution, enzyme-gold nanoparticle conjugates (E-GNP), and the
      enzyme-gold nanoparticle conjugates immobilized in capillary (E-GNP-C) were
      investigated in detail with the proposed MCE-LIF method. Moreover, for optimizing
      the enzymatic reaction efficiency, three important parameters, including the
      length of capillary, the enzyme concentration reacted with gold nanoparticle and
      the amount of L-Asnase immobilized on the gold nanoparticle, have been studied.
      Owing to the high specific activity, the E-GNP-C enzyme reactor exhibited the
      best performance for the hydrolysis of L-Gln.

PMID- 23161489
TI  - Convergence of the ZMIZ1 and NOTCH1 pathways at C-MYC in acute T lymphoblastic
      leukemias.
AB  - Activating NOTCH1 mutations are found in 50% to 60% of human T-cell acute
      lymphoblastic leukemia (T-ALL) samples. In mouse models, these mutations
      generally fail to induce leukemia. This observation suggests that NOTCH1
      activation must collaborate with other genetic events. Mutagenesis screens
      previously implicated ZMIZ1 as a possible NOTCH1 collaborator in leukemia. ZMIZ1
      is a transcriptional coactivator of the protein inhibitor of activated STAT
      (PIAS)-like family. Its role in oncogenesis is unknown. Here, we show that
      activated NOTCH1 and ZMIZ1 collaborate to induce T-ALL in mice. ZMIZ1 and
      activated NOTCH1 are coexpressed in a subset of human T-ALL patients and cell
      lines. ZMIZ1 inhibition slowed growth and sensitized leukemic cells to
      corticosteroids and NOTCH inhibitors. Gene expression profiling identified C-MYC,
      but not other NOTCH-regulated genes, as an essential downstream target of ZMIZ1.
      ZMIZ1 functionally interacts with NOTCH1 to promote C-MYC transcription and
      activity. The mechanism does not involve the NOTCH pathway and appears to be
      indirect and mediated independently of canonical PIAS functions through a novel N
      terminal domain. Our study shows the importance of identifying genetic
      collaborations between parallel leukemic pathways that may be therapeutically
      targeted. They also raise new inquiries into potential NOTCH-ZMIZ1 collaboration
      in a variety of C-MYC-driven cancers.

PMID- 23161491
TI  - Transparent high-performance thin film transistors from solution-processed SnO2
      /ZrO2 gel-like precursors.
AB  - This work employs novel SnO(2) gel-like precursors in conjunction with sol-gel
      deposited ZrO(2) gate dielectrics to realize high-performance transparent
      transistors. Representative devices show excellent performance and transparency,
      and deliver mobility of 103 cm(2) V(-1) s(-1) in saturation at operation voltages
      as low as 2 V, a sub-threshold swing of only 0.3 V/decade, and /(on) //(off) of
      10(4) ~10(5) .

PMID- 23161490
TI  - Augmenting antitumor T-cell responses to mimotope vaccination by boosting with
      native tumor antigens.
AB  - Vaccination with antigens expressed by tumors is one strategy for stimulating
      enhanced T-cell responses against tumors. However, these peptide vaccines rarely
      result in efficient expansion of tumor-specific T cells or responses that protect
      against tumor growth. Mimotopes, or peptide mimics of tumor antigens, elicit
      increased numbers of T cells that crossreact with the native tumor antigen,
      resulting in potent antitumor responses. Unfortunately, mimotopes may also elicit
      cells that do not crossreact or have low affinity for tumor antigen. We
      previously showed that one such mimotope of the dominant MHC class I tumor
      antigen of a mouse colon carcinoma cell line stimulates a tumor-specific T-cell
      clone and elicits antigen-specific cells in vivo, yet protects poorly against
      tumor growth. We hypothesized that boosting the mimotope vaccine with the native
      tumor antigen would focus the T-cell response elicited by the mimotope toward
      high affinity, tumor-specific T cells. We show that priming T cells with the
      mimotope, followed by a native tumor-antigen boost, improves tumor immunity
      compared with T cells elicited by the same prime with a mimotope boost. Our data
      suggest that the improved tumor immunity results from the expansion of mimotope
      elicited tumor-specific T cells that have increased avidity for the tumor
      antigen. The enhanced T cells are phenotypically distinct and enriched for T-cell
      receptors previously correlated with improved antitumor immunity. These results
      suggest that incorporation of native antigen into clinical mimotope vaccine
      regimens may improve the efficacy of antitumor T-cell responses.

PMID- 23161492
TI  - Modulation of the natural killer cell KIR repertoire by cytomegalovirus
      infection.
AB  - Patients carrying activating killer cell immunoglobulin-like receptor (KIR) genes
      are significantly protected from CMV-associated complications after solid organ
      or hematopoietic stem cell transplantation. Whether previous infection with CMV
      affects NK-cell function in healthy donors is unknown. We studied the KIR
      repertoire and alterations of KIR expression after in vitro exposure to CMV in 54
      healthy donors. The expression of neither activating nor inhibitory KIRs was
      different at baseline between 23 seropositive and 31 seronegative donors.
      However, after co-culture of NK cells with CMV-infected fibroblast cells,
      expression of the inhibitory receptors KIR2DL1 and KIR2DL3 and the activating
      receptor KIR3DS1 significantly increased in CMV-seropositive donors. In CMV
      seronegative donors, changes were subtle and restricted to the subset of NK cells
      expressing NK-cell group antigen 2C (NKG2C). Expansion of inhibitory KIRs
      occurred exclusively in donors carrying the cognate HLA class I ligands, whereas
      the presence of the putative ligand HLA-Bw4 was not necessary for the expansion
      of KIR3DS1-expressing NK cells. Our data show that previous infection with CMV
      does not alter the resting NK-cell receptor repertoire, but appears to modify how
      NK cells respond to re-exposure to CMV in vitro.

PMID- 23161493
TI  - Recent advances in the combination of capillary electrophoresis with mass
      spectrometry: from element to single-cell analysis.
AB  - This overview deals with the latest development of electrophoresis in capillaries
      and microfluidic devices coupled to MS detection. A wide selection of relevant
      articles covers the literature published from January 2010 till June 2012 as a
      continuation of the review article on the same topic by Pantuckova et al.
      [Electrophoresis 2011, 32, 43-51]. Special attention is paid to the new
      improvements in instrumentation and methodology of three interfacing methods,
      ESI, matrix-assisted desorption/ionization, and ICP. Representative examples
      illustrate applications in the proteomics, glycomics, metabolomics, biomarker
      research, forensics, pharmacology, food analysis and single-cell analysis. The
      combinations of MS with capillary versions of electrochromatography, ITP, IEF,
      and micellar electrokinetic chromatography are not included.

PMID- 23161494
TI  - Measurement of brain activation during an upright stepping reaction task using
      functional near-infrared spectroscopy.
AB  - Functional near-infrared spectroscopy (fNIRS) is a non-invasive brain imaging
      technology that uses light to measure changes in cortical hemoglobin
      concentrations. FNIRS measurements are recorded through fiber optic cables, which
      allow the participant to wear the fNIRS sensors while standing upright. Thus,
      fNIRS technology is well suited to study cortical brain activity during upright
      balance, stepping, and gait tasks. In this study, fNIRS was used to measure
      changes in brain activation from the frontal, motor, and premotor brain regions
      during an upright step task that required subjects to step laterally in response
      to visual cues that required executive function control. We hypothesized that
      cognitive processing during complex stepping cues would elicit brain activation
      of the frontal cortex in areas involved in cognition. Our results show increased
      prefrontal activation associated with the processing of the stepping cues.
      Moreover, these results demonstrate the potential to use fNIRS to investigate
      cognitive processing during cognitively demanding balance and gait studies.

PMID- 23161495
TI  - Hypothermic regulation of astrocyte proteome profile in experimental stroke.
AB  - Astrocytes provide physical and metabolic support for neurons in the central
      nervous system. Reactive astrocytes, however, play a crucial role in
      neuroinflammation after brain injury. Therapeutic hypothermia has been shown to
      be neuroprotective in brain injury patients. In order to understand the effect of
      therapeutic hypothermia on astrocytes in stroke patients, we performed a
      proteomic profiling of astrocytes following transient focal cerebral ischemia in
      rats under normothermic (37 degrees C) or mild hypothermic condition (33 degrees
      C). Primary astrocytes were prepared from rat brain using a Percoll gradient
      method, and their proteome profiles were determined by using LC/ESI-MS/MS
      followed by high-throughput label-free quantification. Comparison of proteome
      profiles of astrocytes following transient focal ischemia revealed that
      hypothermia upregulated (>=1.5-fold) 86 proteins and downregulated (<=0.6-fold)
      47 proteins compared to normothermic condition. The changes of protein expression
      were validated by Western blot or RT-PCR. Ingenuity Pathways Analysis and
      Database for Annotation, Visualization and Integrated Discovery analyses of the
      up- or downregulated proteins indicate that hypothermia influences glutamatergic
      signaling, cell death, and stress response of astrocytes in the ischemic brain.
      Therefore, therapeutic hypothermia may be neuroprotective in stroke patients by
      modulating astrocytic functions and survival.

PMID- 23161497
TI  - Which polyesters can mimic polyethylene?
AB  - Self-metathesis of erucic acid by [(PCy(3))(eta-C-C(3)H(4)N(2)Mes(2))Cl(2)Ru =
      CHPh] (Grubbs second- generation catalyst) followed by catalytic hydrogenation
      and purification via the ester yields 1,26-hexacosanedioate (>99% purity).
      Polyesterification with 1,26-hexacosanediol, generated from the diester, affords
      polyester-26,26, which features a T(m) of 114  degrees C (T(c) = 92  degrees C,
      DeltaH(m) = 160 J g(-1)). Ultralong-chain model polyesters-38,23 (T(m) = 109 
      degrees C) and -44,23 (T(m) = 111  degrees C), generated via multistep procedures
      including acyclic diene metathesis polymerization, underline that melting points
      of such aliphatic polyesters do not gradually increase with methylene sequence
      chain length. Available data suggest that to mimic linear polyethylenes thermal
      properties, even longer sequences, amounting to at least four times a fatty acid
      chain, fully incorporated in a linear fashion are required.

PMID- 23161496
TI  - Local hypersensitivity reaction in transgenic mice with squamous epithelial IL-5
      overexpression provides a novel model of eosinophilic oesophagitis.
AB  - OBJECTIVE: Eosinophilic oesophagitis (EoE) is a chronic inflammatory condition of
      the oesophagus with limited treatment options. No previous transgenic model has
      specifically targeted the oesophageal mucosa to induce oesophageal eosinophilia.
      DESIGN: We developed a mouse model that closely resembles EoE by utilising
      oxazolone haptenation in mice with transgenic overexpression of an eosinophil
      poietic and survival factor (interleukin (IL)-5) in resident squamous oesophageal
      epithelia. RESULTS: Overexpression of IL-5 in the healthy oesophagus was achieved
      in transgenic mice (L2-IL5) using the squamous epithelial promoter Epstein-Barr
      virus ED-L2. Oxazolone-challenged L2-IL5 mice developed dose-dependent pan
      oesophageal eosinophilia, including eosinophil microabscess formation and
      degranulation as well as basal cell hyperplasia. Moreover, oesophagi expressed
      increased IL-13 and the eosinophil agonist chemokine eotaxin-1. Treatment of
      these mice with corticosteroids significantly reduced eosinophilia and epithelial
      inflammation. CONCLUSIONS: L2-IL5 mice provide a novel experimental model that
      can potentially be used in preclinical testing of EoE-related therapeutics and
      mechanistic studies identifying pathogenetic features associated with mucosal
      eosinophilia.

PMID- 23161498
TI  - Histopathological lesions and DNA adducts in the liver of European flounder
      (Platichthys flesus) collected in the Seine estuary versus two reference
      estuarine systems on the French Atlantic coast.
AB  - An epidemiological survey was conducted in the Seine estuary and in two smaller
      and relatively preserved estuaries on the French Atlantic coast in order to
      estimate the occurrence of liver lesions in European flounder, Platichthys
      flesus, and also to seek putative risk factors for the recorded pathologies. Four
      hundred and seventy-eight fish of both sexes and of different size ranges were
      sampled in the three studied areas, 338 of which in the Seine estuary. All fish
      were examined for histopathological liver lesions, while DNA adducts and otoliths
      were analyzed on a subsample. Five categories of hepatic lesions were recorded
      with the following prevalence for the Seine estuary: 36.7 % inflammations, 8 %
      parasites (mainly encysted nematodes), 6.5 % foci of cellular alteration (FCA),
      5.3 % foci of necrosis or regeneration (FNR), and 1.5 % tumors. Inflammation
      occurrence increased according to age, contrary to parasitic infestations and FCA
      which were more prevalent in young fish, notably those of <1 year old (group 0).
      Tumors were only observed in females of more than two winters. Females exhibited
      a higher prevalence of tumors (3.0 %) and FCA (6.5 %) than males (0 and 2.6 %,
      respectively). Parasitic and infectious lesions and FNR were equally distributed
      in males and females. The prevalence of FNR was also shown to vary according to
      sampling season, with significantly more occurrences of liver necrosis in the
      fish collected in summer than in spring. Spatial differences were observed with a
      higher occurrence of encysted parasites in flounders from the upper Seine
      estuary, while inflammations predominated in flounders living downstream.
      Temporal trends were also noted, with an increased prevalence of parasitic
      infestations, inflammations, and FCA in the 2002-2003 period in comparison to the
      1996-1997 one. The three flounder populations from the Seine estuary (Normandy),
      Ster estuary (Brittany), and Bay of Veys (Normandy) showed different spectra of
      hepatic lesions. Flounders from the Bay of Veys had relatively few liver lesions
      as compared to flounders from the two other estuaries. Flounders from the Ster
      estuary exhibited the highest prevalence of parasites (37.2 %) and inflammations
      (51.1 %). Finally, FCA and liver tumors occurred at very similar levels in both
      flounder populations from the Seine and the Ster estuaries. Group 0 flounders
      inhabiting the upper Seine estuary were more prone to parasitic and pre
      neoplastic hepatic lesions and had higher levels of liver DNA adducts than the
      older ones living downstream. It was postulated that group 0 European flounders
      may serve as valuable bioindicators for assessing the quality of estuarine waters
      and the health status of euryhaline fish populations.

PMID- 23161499
TI  - Lead accumulation and association with Fe on Typha latifolia root from an urban
      brownfield site.
AB  - Synchrotron X-ray microfluorescence and X-ray absorption near-edge microstructure
      spectroscopy techniques were applied to Typha latifolia (cattail) root sections
      and rhizosphere soils collected from a brownfield site in New Jersey to
      investigate lead (Pb) accumulation in T. latifolia roots and the role of iron
      (Fe) plaque in controlling Pb uptake. We found that Pb and Fe spatial
      distribution patterns in the root tissues are similar with both metals present at
      high concentrations mainly in the epidermis and at low concentrations in the
      vascular tissue (xylem and phloem), and the major Pb and Fe species in T.
      latifolia root are Pb(II) and Fe(III) regardless of concentration levels. The
      sequestration of Pb by T. latifolia roots suggests a potential low-cost
      remediation method (phytostabilization) to manage Pb-contaminated sediments for
      brownfield remediation while performing wetland rehabilitation.

PMID- 23161500
TI  - Co-treatment of acid mine drainage with municipal wastewater: performance
      evaluation.
AB  - Co-treatment of acid mine drainage (AMD) with municipal wastewater (MWW) using
      the activated sludge process is a novel treatment technology offering potential
      savings over alternative systems in materials, proprietary chemicals and energy
      inputs. The impacts of AMD on laboratory-scale activated sludge units (plug-flow
      and sequencing batch reactors) treating synthetic MWW were investigated.
      Synthetic AMD containing Al, Cu, Fe, Mn, Pb, Zn and SO4 at a range of
      concentrations and pH values was formulated to simulate three possible co
      treatment processes, i.e., (1) adding raw AMD to the activated sludge aeration
      tank, (2) pre-treating AMD prior to adding to the aeration tank by mixing with
      digested sludge and (3) pre-treating AMD by mixing with screened MWW. Continuous
      AMD loading to the activated sludge reactors during co-treatment did not cause a
      significant decrease in chemical oxygen demand (COD), 5-day biochemical oxygen
      demand, or total organic carbon removal; average COD removal rates ranged from 87
      93%. Enhanced phosphate removal was observed in reactors loaded with Fe- and Al
      rich AMD, with final effluent TP concentrations<2 mg/L. Removal rates for
      dissolved Al, Cu, Fe and Pb were 52-84%, 47-61%, 74-86% and 100%, respectively,
      in both systems. Manganese and Zn removal were strongly linked to acidity;
      removal from net-acidic AMD was <10% for both metals, whereas removal from circum
      neutral AMD averaged 93-95% for Mn and 58-90% for Zn. Pre-mixing with screened
      MWW was the best process option in terms of AMD neutralization and metal removal.
      However, significant MWW alkalinity was consumed, suggesting an alkali supplement
      may be necessary.

PMID- 23161501
TI  - Titania-supported silver-based bimetallic nanoparticles as photocatalysts.
AB  - Photocatalytic process has shown recently a great potential as an environmental
      friendly and clean remediation technology for organic pollutants in wastewater.
      This work described the synthesis of silver-based bimetallic nanoparticles using
      colloid chemistry and the subsequent immobilization onto titania to form
      composite photocatalytic materials (titania-supported Ag-Pt nanoparticles). The
      photocatalysts were characterized by X-ray diffraction, electron microscopy, and
      nitrogen physisorption. The catalytic activity of the photocatalysts was
      evaluated by photocatalytic degradation of phenol and 2-chlorophenol (2-CP) in
      synthetic wastewater solutions. The photocatalytic processes were conducted in a
      batch photoreactor containing appropriate solutions of phenol and 2-CP with UV
      irradiation of 450 W. UV-visible spectrophotometer was used for analyzing the
      concentration of phenol and 2-CP in solutions. Parameters affecting the
      photocatalytic process such as the solution pH, phenol and 2-CP concentrations,
      and catalyst concentration were investigated. The results obtained revealed that
      TiO(2)-supported Ag/Pt nanoparticles showed a higher activity for UV
      photocatalytic degradation of both phenol and 2-CP pollutants in the solution (as
      compared to the plain rutile TiO(2)). The photodegradation processes were
      optimized by the 0.5-g/L catalyst with a pollutant concentration of 50 mg/L for
      all the samples. Complete degradation for both phenol and 2-CP was achieved after
      120 min.

PMID- 23161502
TI  - Low field-relevant tebufenozide concentrations affect reproduction in Chironomus
      riparius (Diptera: Chironomidae) in a long-term toxicity test.
AB  - A few studies reporting the effects of tebufenozide, a non-steroidal ecdysone
      agonist that mimics natural moulting hormones in chironomids exist in the
      literature. However, nothing is known about its chronic or multigenerational
      effects on the reproduction of aquatic insects, although tebufenozide is present
      in aquatic ecosystems. Here, we investigated the chronic toxicity of tebufenozide
      in two successive generations of Chironomus riparius using nominal concentrations
      that ranged from 4 to 26.2 MUg/L. We started the test from the first instar
      larvae in the parental (P) generation, quantifying life cycle parameters
      (emergence, sex ratio, development rate, fecundity and fertility) until the
      emergence in the subsequent F1 generation. Results showed a reduction in
      reproduction and a significant decrease in male developmental rate of midges for
      all treatments, in the F1 generation compared with the P generation (paired t
      test; p<0.001). Two-way analysis of variance revealed a significant exposure *
      generation effect on male fraction with male fraction increasing (P generation)
      or decreasing (F1 generation) with increasing exposure. These effects on C.
      riparius underline the importance of conducting long-term studies with
      environmentally relevant concentrations to investigate population-level endpoints
      for endocrine disrupting chemicals.

PMID- 23161503
TI  - Mechanistic studies on the transformation of ethanol into ethene over Fe-ZSM-5
      zeolite.
AB  - Ethanol, through the utilization of bioethanol as a chemical resource, has
      received considerable industrial attention as it provides an alternative route to
      produce more valuable hydrocarbons. Using a density functional theory approach
      incorporating the M06-L functional, which includes dispersion interactions, a
      large 34T nanocluster model of Fe-ZSM-5 zeolite in which T is a Si or Al atom is
      employed to examine both the stepwise and concerted mechanisms of the
      transformation of ethanol into ethene. For the stepwise mechanism, ethanol
      dehydration commences from the first hydrogen abstraction of the ethanol OH group
      to form the ethoxide-hydroxide intermediate with a low activation energy of 17.7
      kcal mol(-1). Consequently, the ethoxide-hydroxide intermediate is decomposed
      into ethene through hydrogen abstraction from the ethoxide methyl carbon to
      either the OH group of hydroxide or the oxygen of the ethoxide group with high
      activation energies of 64.8 and 63.5 kcal mol(-1), respectively. For the
      concerted mechanism, ethanol transformation into the ethene product occurs in a
      single step without intermediate formation, with an activation energy of 32.9
      kcal mol(-1).

PMID- 23161504
TI  - Meta-analysing randomised controlled trials with omega-3 fatty acids in
      cardiovascular disease.

PMID- 23161505
TI  - Initiation of long-acting reversible contraceptive methods (IUDs and implant) at
      pregnancy termination reduces repeat abortion.

PMID- 23161506
TI  - Home-like environments for labour and birth: benefits for women and babies.

PMID- 23161507
TI  - One iron pill a day keeps fatigue away?

PMID- 23161508
TI  - Rapid superparamagnetic-beads-based automated immunoseparation of Zn-proteins
      from Staphylococcus aureus with nanogram yield.
AB  - Pathogenic bacteria have become a serious socio-economic concern. Immunomagnetic
      separation-based methods create new possibilities for rapidly recognizing many of
      these pathogens. The aim of this study was to use superparamagnetic particles
      based fully automated instrumentation to isolate pathogen Staphylococcus aureus
      and its Zn(II) containing proteins (Zn-proteins). The isolated bacteria were
      immediately purified and disintegrated prior to immunoextraction of Zn-proteins
      by superparamagnetic beads modified with chicken anti-Zn(II) antibody. S. aureus
      culture was treated with ZnCl(2). Optimal pathogen isolation and subsequent
      disintegration assay steps were carried out with minimal handling. (i)
      Optimization of bacteria capturing: Superparamagnetic microparticles composed of
      human IgG were used as the binding surface for acquiring live S. aureus. The
      effect of antibodies concentration, ionic strength, and incubation time was
      concurrently investigated. (ii) Optimization of zinc proteins isolation: pure and
      intact bacteria isolated by the optimized method were sonicated. The extracts
      obtained were subsequently analyzed using superparamagnetic particles modified
      with chicken antibody against zinc(II) ions. (iii) Moreover, various types of
      bacterial zinc(II) proteins precipitations from particle-surface interactions
      were tested and associated protein profiles were identified using SDS-PAGE. Use
      of a robotic pipetting system sped up sample preparation to less than 4 h. Cell
      lysis and Zn-protein extractions were obtained from a minimum of 100 cells with
      sufficient yield for SDS-PAGE (tens ng of proteins). Zn(II) content and cell
      count in the extracts increased exponentially. Furthermore, Zn(II) and proteins
      balances were determined in cell lysate, extract, and retentate.

PMID- 23161509
TI  - Cholesterol screening and management in children and young adults should start
      early--NO!
AB  - In 2011, an expert panel from the National Heart, Lung, and Blood Institute
      released recommendations for universal lipid screening and treatment of high
      cholesterol in children. There is no evidence that universal screening will help
      children lead longer, healthier lives. These recommendations will, however, fuel
      the epidemic of overtreatment that is currently threatening our healthcare system
      and our patients.

PMID- 23161510
TI  - Alloparental responsiveness to newborns by nonreproductive, adult male, common
      marmosets (Callithrix jacchus).
AB  - Parental care in mammals is influenced by sensory stimuli from infants, and by
      changes in the hormone levels of caretakers. To determine the responsiveness to
      infant cues in nonreproductive adult male common marmosets (Callithrix jacchus)
      with and without previous experience in caretaking, we exposed 12 males to
      newborn marmosets and assessed their cortisol plasma levels and behavioral
      response. Newborn marmosets housed in transparent enclosures were placed inside
      the cages of the adult male subjects. Males were exposed four times to two
      different experimental conditions: (a) newborn enclosures remained closed during
      the observation period and (b) newborn enclosures were opened during the
      observation period to allow direct social interaction by the adult males. Blood
      samples from adult males were collected after each behavioral observation trial
      to measure the levels of cortisol. The behavioral responses of adult males
      exposed to the closed and open newborn enclosures showed a significant difference
      only with respect to the frequency of displacements, where males moved among the
      quadrants of their own cages with greater frequency when the newborn enclosure
      was sealed. Experienced males approached newborn enclosures more frequently,
      spent more time in close proximity, and carried and recovered newborns more
      quickly than inexperienced males. The successive exposure to newborns increased
      the responsiveness in inexperienced males. The highest levels of plasma cortisol
      in adult males were recorded following periods of exposure to the sealed newborn
      enclosures. This suggests that successive exposure to newborns and previous
      alloparental caregiving experience while living in family groups influences the
      responsiveness of male marmosets to the sensory cues of newborns.

PMID- 23161511
TI  - Evidence of solubility of the acetylide ion C2(2-): syntheses and crystal
      structures of K2C2?2 NH3, Rb2C2?2 NH3, and Cs2C2?7 NH3.
AB  - Carbon anions in solution: C(2)(2-) dumbbells are well-known in solid-state
      compounds. The crystallization of the title compounds now shows that acetylide
      ions are existent in solution and therefore chemistry with small dissolved carbon
      anions may be within reach.

PMID- 23161512
TI  - A method for assessing the potential for confounding applied to ionic strength in
      central Appalachian streams.
AB  - Causal relationships derived from field data are potentially confounded by
      variables that are correlated with both the cause and its effect. The present
      study presents a method for assessing the potential for confounding and applies
      it to the relationship between ionic strength and impairment of benthic
      invertebrate assemblages in central Appalachian streams. The method weighs all
      available evidence for and against confounding by each potential confounder. It
      identifies 10 types of evidence for confounding, presents a qualitative scoring
      system, and provides rules for applying the scores. Twelve potential confounders
      were evaluated: habitat, organic enrichment, nutrients, deposited sediments, pH,
      selenium, temperature, lack of headwaters, catchment area, settling ponds,
      dissolved oxygen, and metals. One potential confounder, low pH, was found to be
      biologically significant and eliminated by removing sites with pH < 6. Other
      potential confounders were eliminated based on the weight of evidence. This
      method was found to be useful and defensible. It could be applied to other
      environmental assessments that use field data to develop causal relationships,
      including contaminated site remediation or management of natural resources.

PMID- 23161513
TI  - Proteomic analysis of exosomes from mutant KRAS colon cancer cells identifies
      intercellular transfer of mutant KRAS.
AB  - Activating mutations in KRAS occur in 30% to 40% of colorectal cancers. How
      mutant KRAS alters cancer cell behavior has been studied intensively, but non
      cell autonomous effects of mutant KRAS are less understood. We recently reported
      that exosomes isolated from mutant KRAS-expressing colon cancer cells enhanced
      the invasiveness of recipient cells relative to exosomes purified from wild-type
      KRAS-expressing cells, leading us to hypothesize mutant KRAS might affect
      neighboring and distant cells by regulating exosome composition and behavior.
      Herein, we show the results of a comprehensive proteomic analysis of exosomes
      from parental DLD-1 cells that contain both wild-type and G13D mutant KRAS
      alleles and isogenically matched derivative cell lines, DKO-1 (mutant KRAS allele
      only) and DKs-8 (wild-type KRAS allele only). Mutant KRAS status dramatically
      affects the composition of the exosome proteome. Exosomes from mutant KRAS cells
      contain many tumor-promoting proteins, including KRAS, EGFR, SRC family kinases,
      and integrins. DKs-8 cells internalize DKO-1 exosomes, and, notably, DKO-1
      exosomes transfer mutant KRAS to DKs-8 cells, leading to enhanced three
      dimensional growth of these wild-type KRAS-expressing non-transformed cells.
      These results have important implications for non-cell autonomous effects of
      mutant KRAS, such as field effect and tumor progression.

PMID- 23161515
TI  - Synthesis of ortho-acylphenols through the palladium-catalyzed ketone-directed
      hydroxylation of arenes.
AB  - Ketone in charge: a formal ketone-directed palladium-catalyzed ortho
      hydroxylation of arenes has been developed as an effective approach to access o
      acylphenols from simple arylketones. A Pd-catalyzed oxidative ortho-carbonylation
      reaction using ketone directing groups to access a ketal-lactone motif is also
      demonstrated. The ubiquity and versatile nature of ketones make these methods
      attractive. BTI=PhI(TFA)(2); DCE=1,2-dichloroethane.

PMID- 23161514
TI  - Human sperm tail proteome suggests new endogenous metabolic pathways.
AB  - Proteomic studies are contributing greatly to our understanding of the sperm
      cell, and more detailed descriptions are expected to clarify additional cellular
      and molecular sperm attributes. The aim of this study was to characterize the
      subcellular proteome of the human sperm tail and, hopefully, identify less
      concentrated proteins (not found in whole cell proteome studies). Specifically,
      we were interested in characterizing the sperm metabolic proteome and gaining new
      insights into the sperm metabolism issue. Sperm were isolated from
      normozoospermic semen samples and depleted of any contaminating leukocytes. Tail
      fractions were obtained by means of sonication followed by sucrose-gradient
      ultracentrifugation, and their purity was confirmed via various techniques.
      Liquid chromatography and tandem mass spectrometry of isolated sperm tail
      peptides resulted in the identification of 1049 proteins, more than half of which
      had not been previously described in human sperm. The categorization of proteins
      according to their function revealed two main groups: proteins related to
      metabolism and energy production (26%), and proteins related to sperm tail
      structure and motility (11%). Interestingly, a great proportion of the metabolic
      proteome (24%) comprised enzymes involved in lipid metabolism, including enzymes
      for mitochondrial beta-oxidation. Unexpectedly, we also identified various
      peroxisomal proteins, some of which are known to be involved in the oxidation of
      very long chain fatty acids. Analysis of our data using Reactome suggests that
      both mitochondrial and peroxisomal pathways might indeed be active in sperm, and
      that the use of fatty acids as fuel might be more preponderant than previously
      thought. In addition, incubation of sperm with the fatty acid oxidation inhibitor
      etomoxir resulted in a significant decrease in sperm motility. Contradicting a
      common concept in the literature, we suggest that the male gamete might have the
      capacity to obtain energy from endogenous pools, and thus to adapt to putative
      exogenous fluctuations.

PMID- 23161516
TI  - A novel andrographolide derivative AL-1 exerts its cytotoxicity on K562 cells
      through a ROS-dependent mechanism.
AB  - Andrographolide-lipoic acid conjugate (AL-1) is a new in-house synthesized
      chemical entity, which was derived by covalently linking andrographolide with
      lipoic acid. However, its anti-cancer effect and cytotoxic mechanism remains
      unknown. In this study, we found that AL-1 could significantly inhibit cell
      viability of human leukemia K562 cells by inducing G2/M arrest and apoptosis in a
      dose-dependent manner. Thirty-one AL-1-regulated protein alterations were
      identified by proteomics analysis. Gene ontology and ingenuity pathway analysis
      revealed that a cluster of proteins of oxidative redox state and apoptotic cell
      death-related proteins, such as PRDX2, PRDX3, PRDX6, TXNRD1, and GLRX3, were
      regulated by AL-1. Functional studies confirmed that AL-1 induced apoptosis of
      K562 cells through a ROS-dependent mechanism, and anti-oxidant, N-acetyl-L
      cysteine, could completely block AL-1-induced cytotoxicity, implicating that ROS
      generation played a vital role in AL-1 cytotoxicity. Accumulated ROS resulted in
      oxidative DNA damage and subsequent G2/M arrest and mitochondrial-mediated
      apoptosis. The current work reveals that a novel andrographolide derivative AL-1
      exerts its anticancer cytotoxicity through a ROS-dependent DNA damage and
      mitochondrial-mediated apoptosis mechanism.

PMID- 23161518
TI  - Characterization of internal structure of hydrated agar and gelatin matrices by
      cryo-SEM.
AB  - There has been a considerable interest in recent years in developing polymer gel
      matrices for many important applications such as 2DE for quantization and
      separation of a variety of proteins and drug delivery system to control the
      release of active agents. However, a well-defined knowledge of the
      ultrastructures of the gels has been elusive. In this study, we report the
      characterization of two different polymers used in 2DE: Gelatin, a naturally
      occurring polymer derived from collagen (protein) and agar, a polymer of
      polysaccharide (sugar) origin. Low-temperature SEM is used to examine the
      internal structure of these gels in their frozen natural hydrated states. Results
      of this study show that both polymers have an array of hollow cells that
      resembles honeycomb structures. While agar pores are almost circular, the
      corresponding Gaussian curve is very broad exhibiting a range of radii from
      nearly 370 to 700 nm. Gelatin pores are smaller and more homogeneous reflecting a
      narrower distribution from nearly 320 to 650 nm. Overall, these ultrastructural
      findings could be used to correlate with functions of the polymers.

PMID- 23161517
TI  - Incorporating network structure in integrative analysis of cancer prognosis data.
AB  - In high-throughput cancer genomic studies, markers identified from the analysis
      of single datasets may have unsatisfactory properties because of low sample
      sizes. Integrative analysis pools and analyzes raw data from multiple studies,
      and can effectively increase sample size and lead to improved marker
      identification results. In this study, we consider the integrative analysis of
      multiple high-throughput cancer prognosis studies. In the existing integrative
      analysis studies, the interplay among genes, which can be described using the
      network structure, has not been effectively accounted for. In network analysis,
      tightly connected nodes (genes) are more likely to have related biological
      functions and similar regression coefficients. The goal of this study is to
      develop an analysis approach that can incorporate the gene network structure in
      integrative analysis. To this end, we adopt an AFT (accelerated failure time)
      model to describe survival. A weighted least squares approach, which has low
      computational cost, is adopted for estimation. For marker selection, we propose a
      new penalization approach. The proposed penalty is composed of two parts. The
      first part is a group MCP penalty, and conducts gene selection. The second part
      is a Laplacian penalty, and smoothes the differences of coefficients for tightly
      connected genes. A group coordinate descent approach is developed to compute the
      proposed estimate. Simulation study shows satisfactory performance of the
      proposed approach when there exist moderate-to-strong correlations among genes.
      We analyze three lung cancer prognosis datasets, and demonstrate that
      incorporating the network structure can lead to the identification of important
      genes and improved prediction performance.

PMID- 23161519
TI  - Improved correspondence of resting-state networks after macroanatomical
      alignment.
AB  - Resting state brain activity, as measured with functional magnetic resonance
      imaging (fMRI) in the absence of stimulation, is widely investigated in clinical,
      pharmacological, developmental and cross-species neuroscience research. However,
      despite the general and broad interest in understating the nature of resting
      state networks (RSNs), there has not been a thorough investigation into the
      relationship between these functional networks and their adherence to underling
      brain anatomy. We acquired resting state fMRI data from 10 subjects and extracted
      individual and group RSN maps respectively using independent component analysis
      (ICA) and self organising group-level ICA (sogICA). Cortex based alignment (CBA),
      an advanced surface based alignment technique which uses individual curvature
      information to align individual subjects' brains to a dynamic group average, was
      used to maximise anatomical correspondence across subjects. Cross subject spatial
      correlations of the RSN maps (independent components) were carried out with and
      without CBA. Seven RSNs, which are amongst the most reported and studied
      networks, were identified. We observed a systematic gain in the spatial
      correlation in all of them following CBA, although this gain was not uniform
      across RSNs. The observed increase in similarity of the functional RSNs after
      anatomical alignment illustrates that these functional networks are indeed
      related to underlying macroanatomical features. Moreover, our results demonstrate
      that by correcting for individual anatomical differences, advanced surface based
      alignment techniques increase the overlap of corresponding resting state networks
      across subjects, thereby providing a useful means to improve resting state group
      statistics with no need for substantial smoothing.

PMID- 23161520
TI  - CE-MS for the analysis of intact proteins 2010-2012.
AB  - Since its introduction in 1987, CE-MS has become an increasingly important
      technique for the analysis of biomolecules. Since our previous update on CE-MS
      methods within the field of intact protein analysis (Electrophoresis 2011, 32, 66
      82), a variety of interesting methodological improvements and applications have
      been reported in literature. Therefore, this article presents an overview of the
      development and application of CE-MS for intact protein analysis as published
      between June 2010 and June 2012. The article is divided in sections that treat CE
      coupled to MS through ESI, MALDI, and ICP ionization, respectively. In the
      section about CE-ESI-MS, technological developments with respect to CE-MS
      interfacing, prevention of protein adsorption, and chip-based CE-MS are treated
      in more detail. Novel interfacing strategies and the development of improved
      capillary coating strategies appeared to be the major developments. Furthermore,
      in all sections, the applicability of CE-MS for intact protein analysis is
      demonstrated by representative examples, including important developments in the
      fields of biopharmaceutical characterization and the analysis of proteins in
      biological samples. Finally, some general conclusions and future perspectives are
      given.

PMID- 23161521
TI  - Substituent variation drives metal/monolayer/semiconductor junctions from
      strongly rectifying to ohmic behavior.
AB  - An eight-orders of magnitude enhancement in current across Hg/X-styrene-Si
      junctions is caused by merely altering a substituent, X. Interface states are
      passivated and, depending on X, the Si Schottky junction encompasses the full
      range from Ohmic to strongly rectifying. This powerful electrostatic molecular
      effect has immediate implications for interface band alignment and sensing.

PMID- 23161522
TI  - Detection of human papillomavirus in sinonasal papillomas: systematic review and
      meta-analysis.
AB  - OBJECTIVES/HYPOTHESIS: To perform a systematic review and formal meta-analysis of
      the literature reporting on HPV detection in sinonasal papillomas. Since first
      reported in 1983, the etiological role for human papillomavirus (HPV) in
      sinonasal papillomas has been subject to increasing interest. STUDY DESIGN: A
      systematic review, with meta-analysis and formal meta-regression. METHODS:
      Literature was searched through April 2012. The effect size was calculated as
      event rates (95% confidence interval [CI]), with homogeneity testing using
      Cochran's Q and I(2) statistics. Meta-regression was used to test the impact of
      study-level covariates (HPV detection method, geographic origin, papilloma type)
      on effect size, and potential publication bias was estimated using funnel plot
      symmetry. RESULTS: Seventy-six studies were eligible covering 1,956 sinonasal
      papillomas from different geographic regions. Altogether, 760 (38.8%) cases
      tested HPV-positive; effect size 0.421 (95% CI 0.359-0.485, random effects
      model). The summary HPV prevalence was highest (65.3%) in exophytic papillomas
      (EP), followed by inverted papillomas (37.8%) and cylindrical cell papillomas
      (22.5%). In meta-analysis stratified by 1) HPV detection technique, 2) geographic
      study origin, and 3) papilloma type, the between-study heterogeneity was
      significant only for the papilloma types (P = .001). In meta-regression, HPV
      detection method (P = .102), geographic origin (P = .149), or histological type
      (P = .240) were not significant study-level covariates. Some evidence for
      publication bias was found only for studies on EP. In sensitivity analysis, all
      meta-analytic results were robust to all one-by-one study removals. CONCLUSIONS:
      Variability in HPV detection rates in sinonasal papillomas is explained by their
      histological types (not by HPV detection method or geographic origin of study),
      but none of the three were significant study-level covariates in formal meta
      regression.

PMID- 23161523
TI  - Neurobehavioral, cellular, and molecular consequences of single and multiple mild
      blast exposure.
AB  - Mild traumatic brain injury, caused by the exposure to single or repeated blast
      overpressure, is a principal concern due to its pathological complexity and
      neurobehavioral similarities with posttraumatic stress disorder. In this study,
      we exposed rats to a single or multiple (five total; administered on consecutive
      days) mild blasts, assessed their behavior at 1 and 16 days postinjury) and
      performed histological and protein analyses of brains and plasma at an early (2
      h) and a late (22 days) termination time point. One day postinjury, multiple
      injured (MI) rats showed the least general locomotion and the most depression-
      and anxiety-related behaviors among the experimental groups; there were no such
      differences at 16 days. However, at the later time point, both injured groups
      displayed elevated levels of select protein biomarkers. Histology showed
      significantly increased numbers of TUNEL+ (terminal-deoxy-transferase-mediated
      dUTP nick-end labeling)-positive cells in the dorsal and ventral hippocampus (DHC
      and VHC) of both injured groups as early as 2 h after injury. At 22 days, the
      increase was limited to the VHC of MI animals. Our findings suggest that the
      exposure to mild blast overpressure triggers early hippocampal cell death as well
      as neuronal, glial, and vascular damage that likely contribute to significant,
      albeit transient increases in depression- and anxiety-related behaviors. However,
      the severity of the observed pathological changes in MI rats failed to support
      the hypothesized cumulative effect of repeated injury. We infer that at this
      blast frequency, a potential conditioning phenomenon counteracts with and reduces
      the extent of subsequent damage in MI rats.

PMID- 23161524
TI  - Exploring the interaction between graphene derivatives and metal ions as a key
      step towards graphene-inorganic nanohybrids.
AB  - The assembly of graphene derivatives and inorganic nanostructures opens up an
      exciting new field in the functionalization of nanomaterials. However, a better
      understanding of the interaction between graphene derivatives and inorganic
      precursors remains a challenge. This work provides an efficient strategy for
      exploring this interaction by first modifying graphene oxide with aniline,
      glycine, and glycyl glycine, respectively, and thus engineering the chemical
      microenvironments on graphene sheets for anchoring metal ions. After that, the
      affinities of graphene derivatives to various metal ions can be investigated with
      the help of a conventional electrochemical method. The method highlights the
      importance of graphene chemistry in hybrid preparation and provides design
      principles for chemical modifiers used in the construction of multifunctional
      carbon-inorganic nanostructures.

PMID- 23161526
TI  - Eu2+ & Mn(2+)-coactivated Ba3Gd(PO4)3 orange-yellow-emitting phosphor with
      tunable color tone for UV-excited white LEDs.
AB  - A novel orange-yellow-emitting Ba(3)Gd(PO(4))(3):xEu(2+),yMn(2+) phosphor is
      prepared by high-temperature solid-state reaction. The crystal structure of
      Ba(3)Gd(PO(4))(3):0.005 Eu(2+),0.04 Mn(2+) is determined by Rietveld refinement
      analysis on powder X-ray diffraction data, which shows that the cations are
      disordered on a single crystallographic site and the oxygen atoms are distributed
      over two partially occupied sites. The photoluminescence excitation spectra show
      that the developed phosphor has an efficient broad absorption band ranging from
      230 to 420 nm, perfectly matching the characteristic emission of UV-light
      emitting diode (LED) chips. The emission spectra show that the obtained phosphors
      possess tunable color emissions from yellowish-green through yellow and
      ultimately to reddish-orange by simply adjusting the Mn(2+) content (y) in
      Ba(3)Gd(PO(4))(3):0.005 Eu(2+),y Mn(2+) host. The tunable color emissions origin
      from the change in intensity between the 4f-5d transitions in the Eu(2+) ions and
      the (4)T(1)-(6)A(1) transitions of the Mn(2+) ions through the energy transfer
      from the Eu(2+) to the Mn(2+) ions. In addition, the mechanism of the energy
      transfer between the Eu(2+) and Mn(2+) ions are also studied in terms of the
      Inokuti-Hirayama theoretical model. The present results indicate that this novel
      orange-yellow-emitting phosphor can be used as a potential candidate for the
      application in white LEDs.

PMID- 23161525
TI  - A multisite study of long-term remission and relapse of type 2 diabetes mellitus
      following gastric bypass.
AB  - BACKGROUND: Gastric bypass has profound effects on glycemic control in adults
      with type 2 diabetes mellitus. The goal of this study was to examine the long
      term rates and clinical predictors of diabetes remission and relapse among
      patients undergoing gastric bypass. METHODS: We conducted a retrospective cohort
      study of adults with uncontrolled or medication-controlled type 2 diabetes who
      underwent gastric bypass from 1995 to 2008 in three integrated health care
      delivery systems in the USA. Remission and relapse events were defined by
      diabetes medication use and clinical laboratory measures of glycemic control. We
      identified 4,434 adults with uncontrolled or medication-controlled type 2
      diabetes who had gastric bypass. RESULTS: Overall, 68.2 % (95 % confidence
      interval [CI], 66 and 70 %) experienced an initial complete diabetes remission
      within 5 years after surgery. Among these, 35.1 % (95 % CI, 32 and 38 %)
      redeveloped diabetes within 5 years. The median duration of remission was 8.3
      years. Significant predictors of complete remission and relapse were poor
      preoperative glycemic control, insulin use, and longer diabetes duration. Weight
      trajectories after surgery were significantly different for never remitters,
      relapsers, and durable remitters (p = 0.03). CONCLUSIONS: Gastric bypass surgery
      is associated with durable remission of type 2 diabetes in many but not all
      severely obese diabetic adults, and about one third experience a relapse within 5
      years of initial remission. More research is needed to understand the mechanisms
      of diabetes relapse, the optimal timing of surgery in effecting a durable
      remission, and the relationship between remission duration and incident
      microvascular and macrovascular events.

PMID- 23161528
TI  - Enhancing amine-supported materials for ambient air capture.

PMID- 23161529
TI  - 35Cl NQR frequency and spin lattice relaxation time in 3,4-dichlorophenol as a
      function of pressure and temperature.
AB  - The pressure dependences of (35)Cl nuclear quadrupole resonance (NQR) frequency,
      temperature and pressure variation of spin lattice relaxation time (T(1)) were
      investigated in 3,4-dichlorophenol. T(1) was measured in the temperature range 77
      300 K. Furthermore, the NQR frequency and T(1) for these compounds were measured
      as a function of pressure up to 5 kbar at 300 K. The temperature dependence of
      the average torsional lifetimes of the molecules and the transition probabilities
      W(1) and W(2) for the Deltam = +/-1 and Deltam = +/-2 transitions were also
      obtained. A nonlinear variation of NQR frequency with pressure has been observed
      and the pressure coefficients were observed to be positive. A thermodynamic
      analysis of the data was carried out to determine the constant volume temperature
      coefficients of the NQR frequency. An attempt is made to compare the torsional
      frequencies evaluated from NQR data with those obtained by IR spectra. On
      selecting the appropriate mode from IR spectra, a good agreement with torsional
      frequency obtained from NQR data is observed. The previously mentioned approach
      is a good illustration of the supplementary nature of the data from IR studies,
      in relation to NQR studies of compounds in solid state.

PMID- 23161530
TI  - The clinical value of echocardiography and acoustic cardiography to monitor
      patients undergoing anthracycline chemotherapy.
AB  - BACKGROUND: Investigate the usefulness of echocardiography and acoustic
      cardiography to monitor patients exposed to anthracycline chemotherapy.
      HYPOTHESIS: Serial echocardiographies to monitor systolic function may not be
      neccessary in all patients undergoing anthracycline chemotherapy. METHODS: In a
      prospective study, consecutive patients undergoing anthracycline-containing
      chemotherapy were evaluated with echocardiography and acoustic cardiography at
      baseline, after completion of chemotherapy, and after a median follow-up of 3.8
      years. Systolic dysfunction was defined as a left ventricular ejection
      fraction<=50%. RESULTS: A total of 187 patients (83% female) with a mean age of
      55+/-14 years underwent chemotherapy for breast cancer (73%), malignant lymphoma
      (23%), and sarcoma (4%). None of the patients had systolic dysfunction at
      baseline. Patients were treated with doxorubicin 276+/-74 mg/m2 or epirubicin
      317+/-55 mg/m2. After chemotherapy, 170 (91%) had normal systolic function, 8
      (4%) developed systolic dysfunction, and 9 (5%) had died. Of those 8 patients
      with systolic dysfunction, 4 (50%) improved to normal systolic function, 1 (13%)
      remained unchanged, and 3 (37%) died. Patients with normal systolic function
      after chemotherapy had a mortality rate of 3.5%, and 1.8% developed late systolic
      dysfunction. Acoustic cardiography-derived percent electromechanical activation
      time>12.4% had a sensitivity of 88% and a specificity of 84% to identify patients
      with systolic dysfunction (area under the receiver operating characteristic curve
      0.87). CONCLUSIONS: Patients with systolic dysfunction early after anthracycline
      treatment had worse outcome. Acoustic cardiography was able to identify these
      patients with a high sensitivity and specificity. Based on the findings of this
      study, we propose a simple algorithm to monitor patients undergoing anthracycline
      containing chemotherapy.

PMID- 23161527
TI  - Mineralization induction effects of osteopontin, bone sialoprotein, and dentin
      phosphoprotein on a biomimetic collagen substrate.
AB  - Native bone tissue is composed of a matrix of collagen, noncollagenous proteins,
      and calcium phosphate minerals, which are primarily hydroxyapatite. The SIBLING
      (small integrin-binding ligand, N-linked glycoprotein) family of proteins is the
      primary noncollagenous protein group found in mineralized tissues. In this work,
      the mineralization induction capabilities of three of the SIBLING members, bone
      sialoprotein (BSP), osteopontin (OPN), and the calcium-binding subdomain of
      dentin sialophosphoprotein, dentin phosphoprotein (DPP), are directly compared on
      a biomimetic collagen substrate. A self-assembled, loosely aligned collagen
      fibril substrate was prepared, and then (125) I-radiolabeled adsorption isotherms
      were developed for BSP, OPN, and DPP. The results showed that BSP exhibited the
      highest binding capacity for collagen at lower concentrations, followed by DPP
      and OPN. However, at the highest concentrations, all three proteins had similar
      adsorption levels. The adsorption isotherms were then used to identify conditions
      that resulted in identical amounts of adsorbed protein. These substrates were
      prepared and placed in simulated body fluid for 5, 10, and 24 h at 37 degrees C.
      The resulting mineral morphology was assessed by atomic force microscopy, and the
      composition was determined using photochemical assays. Mineralization was seen in
      the presence of all the proteins. However, DPP was seen to be the only protein
      that formed individual mineral nodules similar to those seen in developing bone.
      This suggests that DPP plays a significant role in the biomineralization process
      and that the incorporation of DPP into tissue engineering constructs may
      facilitate the induction of biomimetic mineral formation.

PMID- 23161531
TI  - Relationship of land use and elevated ionic strength in Appalachian watersheds.
AB  - Coal mining activities have been implicated as sources that increase stream
      specific conductance in Central Appalachia. The present study characterized
      potential sources of elevated ionic strength for small subwatersheds within the
      Coal, Upper Kanawha, Gauley, and New Rivers in West Virginia. From a large
      monitoring data set developed by the West Virginia Department of Environmental
      Protection, 162 < 20-km(2)-watersheds were identified that had detailed land
      cover information in southwestern West Virginia with at least one water chemistry
      sample. Scatter plots of specific conductance were generated for nine land cover
      classifications: open water, agriculture, forest, residential, barren, total
      mining, valley fill, abandoned mine lands, and mining excluding valley fill and
      abandoned mine lands. Conductivity was negatively correlated with the percentage
      of forest area and positively associated with other land uses. In a multiple
      regression, the percentage of area in valley fill was the strongest contributor
      to increased ionic strength, followed by percentage of area in urban
      (residential/buildings) land use and other mining land use. Based on the 10th
      quantile regression, 300 uS/cm was exceeded at 3.3% of area in valley fill. In
      most catchments, HCO 3(-) and SO 4(2-) concentrations were greater than Cl(-)
      concentration. These findings confirm coal mining activities as the primary
      source of high conductivity waters. Such activities might be redressed with the
      goal of protecting sources of dilute freshwater in the region.

PMID- 23161532
TI  - The synthesis of chiral isotetronic acids with amphiphilic imidazole/pyrrolidine
      catalysts assembled in oil-in-water emulsion droplets.
AB  - Drop it! A highly enantioselective catalytic cascade reaction of alpha-ketoacids
      and aldehydes is achieved using the title catalyst and water as the solvent.
      Fluorescence imaging shows that the catalyst is mainly distributed on the surface
      of emulsion droplets. Optically active isotetronic acids can be obtained with
      this method and the emulsion droplets are responsible for the high reactivity and
      enantioselectivity.

PMID- 23161533
TI  - Alternative visualization of SDS-PAGE separated phosphoproteins by alizarin red S
      aluminum (III)-appended complex.
AB  - A novel fluorescence detection system using a chemosensor for phosphoprotein in
      gel electrophoretic analysis has been developed. The system employed the alizarin
      red S-aluminum (III)-appended complex as a fluorescent staining dye to perform
      the convenient and selective detection of phosphorylated proteins and total
      proteins in SDS-PAGE, respectively. Therefore, a full and selective map of
      proteins can be achieved in the same process without resorting to other
      compatible detection methods. As low as 62.5 ng of alpha- (seven or eight
      phosphates) and beta-casein (five phosphates), 125 ng of ovalbumin (two
      phosphates), and kappa-casein (one phosphate) can be detected in approximately
      135 min, with the linear responses of rigorous quantitation of changes over a 125
      4000 ng range. As a result, alizarin red S-aluminum (III) stain may provide a new
      choice for selective, economic, and convenient visualization of phosphoproteins.

PMID- 23161534
TI  - Label-free aptamer-based partial filling technique for enantioseparation and
      determination of DL-tryptophan with micellar electrokinetic chromatography.
AB  - In this study, a simple and reproducible method for enantioseparation and
      determination of dl-tryptophan (DL-Trp) was developed by using a partial filling
      technique in combination with MEKC. The corresponding L-Trp specific DNA aptamer
      was used as a chiral selector. Sodium cholate was used to form the chiral
      micelles and to enhance the enantioseparation of the enantiomers. Effects of
      aptamer concentration, filling time, buffer composition, and separation voltage
      on the enantioseparation were evaluated. The Mg(2+) and Na(+) concentration in
      separation buffer was found to effectively affect the separation efficiency and
      reproducibility. Under the optimal conditions, D- and L-Trp were completely
      enantioseparated in less than 9 min. This aptamer-based partial-filling approach
      has the potential to be extended to the separation of other enantiomers after the
      replacement of corresponding specific aptamers.

PMID- 23161535
TI  - Time-dependent changes of protein biomarker levels in the cerebrospinal fluid
      after blast traumatic brain injury.
AB  - Time-dependent changes of protein biomarkers in the cerebrospinal fluid (CSF) can
      be used to identify the pathological processes in traumatic brain injury (TBI) as
      well as to follow the progression of the disease. We obtained CSF from a large
      animal model (swine) of blast-induced traumatic brain injury prior to and at 6,
      24, 72 h, and 2 wk after a single exposure to blast overpressure, and determined
      changes in the CSF levels of neurofilament-heavy chain, neuron-specific enolase,
      brain-specific creatine kinase, glial fibrillary acidic protein, calcium-binding
      protein beta (S100beta), Claudin-5, vascular endothelial growth factor, and von
      Willebrand factor using reverse phase protein microarray. We detected biphasic
      temporal patterns in the CSF concentrations of all tested protein markers except
      S100beta. The CSF levels of all markers were significantly increased 6 h after
      the injury compared to preinjury levels. Values were then decreased at 24 h,
      prior to a second increase in all markers but S100beta at 72 h. At 2 wk
      postinjury, the CSF concentrations of all biomarkers were decreased once again;
      brain-specific creatine kinase, Claudin-5, von Willebrand factor, and S100beta
      levels were no longer significantly higher than their preinjury values while
      neurofilament-heavy chain, neuron-specific enolase, vascular endothelial growth
      factor, and glial fibrillary acidic protein levels remained significantly
      elevated compared to baseline. Our findings implicate neuronal and glial cell
      damage, compromised vascular permeability, and inflammation in blast-induced
      traumatic brain injury, as well as demonstrate the value of determining the
      temporal pattern of biomarker changes that may be of diagnostic value.

PMID- 23161536
TI  - Erythema ab igne in an adolescent with anorexia nervosa.
AB  - OBJECTIVE: A rare skin lesion, erythema ab igne (EAI) is presented, in an
      adolescent female with anorexia nervosa. METHOD: Clinical records of this patient
      were compared with a pubmed search about EAI in patients with an eating disorder.
      RESULTS: The patient presented with localized, spider-like, erythematous and
      hyperpigmented skin lesions on the lower abdomen and on both thighs. Repetitive
      exposure to heating pads can induce reticular and macular hyperpigmentation with
      telangiectases without squamation. Strict avoidance of heat is advised, because
      there is no effective treatment. DISCUSSION: EAI is described in patients with an
      eating disorder. Facing an increased pain threshold, prolonged heat exposure to
      treat a general feeling of cold, can induce this dermatosis.

PMID- 23161537
TI  - In vitro MS-based proteomic analysis and absolute quantification of neuronal
      glial injury biomarkers in cell culture system.
AB  - MS-based proteomics has been the method of choice for biomarker discovery in the
      field of traumatic brain injury (TBI). Due to its high sensitivity and
      specificity, MS is now being explored for biomarker quantitative validation in
      tissue and biofluids. In this study, we demonstrate the use of MS in both
      qualitative protein identification and targeted detection of acute TBI biomarkers
      released from degenerating cultured rat cortical mixed neuronal cells, mimicking
      intracellular fluid in the central nervous system after TBI. Calpain activation
      was induced by cell treatment with maitotoxin (MTX), a known calcium channel
      opener. Separate plates of mixed neuronal-glial culture were subjected to
      excitotoxin N-methyl-D-aspartate (NMDA) and apoptotic inducer staurosporine.
      Acute TBI biomarkers, GFAP and UCH-L1, were first detected and assessed in the
      culture media by Western blot. The cell-conditioned media were then trypsinized
      and subjected to bottom up proteomic analysis. GFAP was readily detected by data
      dependent scanning but not UCH-L1. As a proof-of-principle study, rat glia
      enriched cell cultures treated with MTX were used to investigate the time
      dependent release of GFAP breakdown product by Western blot and for isotope
      dilution MS absolute quantitation method development. Absolute quantitation of
      the GFAP release was conducted using the three cortical mixed neuronal cell
      cultures treated with different agents. Other differentially expressed proteins
      identified in the glial-enriched and cortical mixed neuronal cell culture models
      were further analyzed by bioinformatic tools. In summary, this study demonstrates
      the use of MS in both protein identification and targeted quantitation of acute
      TBI biomarkers and is the preliminary step toward development of TBI biomarker
      validation by targeted MS.

PMID- 23161538
TI  - Filamin interacts with epithelial sodium channel and inhibits its channel
      function.
AB  - Epithelial sodium channel (ENaC) in the kidneys is critical for Na(+) balance,
      extracellular volume, and blood pressure. Altered ENaC function is associated
      with respiratory disorders, pseudohypoaldosteronism type 1, and Liddle syndrome.
      ENaC is known to interact with components of the cytoskeleton, but the functional
      roles remain largely unclear. Here, we examined the interaction between ENaC and
      filamins, important actin filament components. We first discovered by yeast two
      hybrid screening that the C termini of ENaC alpha and beta subunits bind filamin
      A, B, and C, and we then confirmed the binding by in vitro biochemical assays. We
      demonstrated by co-immunoprecipitation that ENaC, either overexpressed in HEK,
      HeLa, and melanoma A7 cells or natively expressed in LLC-PK1 and IMCD cells, is
      in the same complex with native filamin. Furthermore, the biotinylation and co
      immunoprecipitation combined assays showed the ENaC-filamin interaction on the
      cell surface. Using Xenopus oocyte expression and two-electrode voltage clamp
      electrophysiology, we found that co-expression of an ENaC-binding domain of
      filamin substantially reduces ENaC channel function. Western blot and
      immunohistochemistry experiments revealed that the filamin A C terminus (FLNAC)
      modestly reduces the expression of the ENaC alpha subunit in oocytes and A7
      cells. After normalizing the current by plasma membrane expression, we found that
      FLNAC results in ~50% reduction in the ENaC channel activity. The inhibitory
      effect of FLNAC was confirmed by lipid bilayer electrophysiology experiments
      using purified ENaC and FLNAC proteins, which showed that FLNAC substantially
      reduces ENaC single channel open probability. Taken together, our study
      demonstrated that filamin reduces ENaC channel function through direct
      interaction on the cell surface.

PMID- 23161539
TI  - The Src substrate SKAP2 regulates actin assembly by interacting with WAVE2 and
      cortactin proteins.
AB  - In our attempt to screen for substrates of Src family kinases in glioblastoma,
      Src kinase-associated phosphoprotein 2 (SKAP2) was identified. Although SKAP2 has
      been suggested to be associated with integrin-mediated adhesion of hematopoietic
      cells, little is known about its molecular function and the effects in other
      types of cells and tumors. Here, we demonstrate that SKAP2 physically associates
      with actin assembly factors WAVE2 and cortactin and inhibits their interaction.
      Cortactin is required for the membrane localization of WAVE2, and SKAP2
      suppresses actin polymerization mediated by WAVE2 and cortactin in vitro.
      Knockdown of SKAP2 in NIH3T3 accelerated cell migration and enhanced
      translocation of WAVE2 to the cell membrane, and those effects of SKAP2 depend on
      the binding activity of SKAP2 to WAVE2. Furthermore, reduction of SKAP2 in the
      glioblastoma promoted tumor invasion both in ex vivo organotypic rat brain slices
      and immune-deficient mouse brains. These results suggest that SKAP2 negatively
      regulates cell migration and tumor invasion in fibroblasts and glioblastoma cells
      by suppressing actin assembly induced by the WAVE2-cortactin complex, indicating
      that SKAP2 may be a novel candidate for the suppressor of tumor progression.

PMID- 23161540
TI  - Acute beta-adrenergic activation triggers nuclear import of histone deacetylase 5
      and delays G(q)-induced transcriptional activation.
AB  - During hemodynamic stress, catecholamines and neurohumoral stimuli may induce co
      activation of G(q)-coupled receptors and beta-adrenergic receptors (beta-AR),
      leading to cardiac remodeling. Dynamic regulation of histone deacetylase 5
      (HDAC5), a transcriptional repressor, is crucial during stress signaling due to
      its role in epigenetic control of fetal gene markers. Little is known about its
      regulation during acute and chronic beta-AR stimulation and its cross-interaction
      with G(q) signaling in adult cardiac myocytes. Here, we evaluate the potential
      cross-talk between G(q)-driven and beta-AR mediated signaling at the level of
      nucleocytoplasmic shuttling of HDAC5. We show the translocation of GFP-tagged
      wild type HDAC5 or mutants (S279A and S279D) in response to beta-AR or G(q)
      agonists. Isoproterenol (ISO) or PKA activation results in strong nuclear
      accumulation of HDAC5 in contrast to nuclear export driven by Ca(2+)-calmodulin
      protein kinase II and protein kinase D. Moreover, nuclear accumulation of HDAC5
      under acute ISO/PKA signaling is dependent on phosphorylation of Ser-279 and can
      block subsequent G(q)-mediated nuclear HDAC5 export. Intriguingly, the
      attenuation of G(q)-induced export is abolished after chronic PKA activation, yet
      nuclear HDAC5 remains elevated. Last, the effect of chronic beta-AR signaling on
      HDAC5 translocation was examined in adult myocytes from a rabbit model of heart
      failure, where ISO-induced nuclear import is ablated, but G(q)-agonist mediated
      export is preserved. Acute beta-AR/PKA activation protects against hypertrophic
      signaling by delaying G(q)-mediated transcriptional activation. This serves as a
      key physiological control switch before allowing genetic reprogramming via HDAC5
      nuclear export during more severe stress, such as heart failure.

PMID- 23161541
TI  - Interplay between alphavbeta3 integrin and nucleolin regulates human endothelial
      and glioma cell migration.
AB  - The multifunctional protein nucleolin (NCL) is overexpressed on the surface of
      activated endothelial and tumor cells and mediates the stimulatory actions of
      several angiogenic growth factors, such as pleiotrophin (PTN). Because
      alpha(v)beta(3) integrin is also required for PTN-induced cell migration, the aim
      of the present work was to study the interplay between NCL and alpha(v)beta(3) by
      using biochemical, immunofluorescence, and proximity ligation assays in cells
      with genetically altered expression of the studied molecules. Interestingly, cell
      surface NCL localization was detected only in cells expressing alpha(v)beta(3)
      and depended on the phosphorylation of beta(3) at Tyr(773) through receptor
      protein-tyrosine phosphatase beta/zeta (RPTPbeta/zeta) and c-Src activation.
      Downstream of alpha(v)beta(3,) PI3K activity mediated this phenomenon and cell
      surface NCL was found to interact with both alpha(v)beta(3) and RPTPbeta/zeta.
      Positive correlation of cell surface NCL and alpha(v)beta(3) expression was also
      observed in human glioblastoma tissue arrays, and inhibition of cell migration by
      cell surface NCL antagonists was observed only in cells expressing
      alpha(v)beta(3). Collectively, these data suggest that both expression and
      beta(3) integrin phosphorylation at Tyr(773) determine the cell surface
      localization of NCL downstream of the RPTPbeta/zeta/c-Src signaling cascade and
      can be used as a biomarker for the use of cell surface NCL antagonists as
      anticancer agents.

PMID- 23161542
TI  - Structural insight into coordinated recognition of trimethylated histone H3
      lysine 9 (H3K9me3) by the plant homeodomain (PHD) and tandem tudor domain (TTD)
      of UHRF1 (ubiquitin-like, containing PHD and RING finger domains, 1) protein.
AB  - UHRF1 is an important epigenetic regulator connecting DNA methylation and histone
      methylations. UHRF1 is required for maintenance of DNA methylation through
      recruiting DNMT1 to DNA replication forks. Recent studies have shown that the
      plant homeodomain (PHD) of UHRF1 recognizes the N terminus of unmodified histone
      H3, and the interaction is inhibited by methylation of H3R2, whereas the tandem
      tudor domain (TTD) of UHRF1 recognizes trimethylated histone H3 lysine 9
      (H3K9me3). However, how the two domains of UHRF1 coordinately recognize histone
      methylations remains elusive. In this report, we identified that PHD largely
      enhances the interaction between TTD and H3K9me3. We present the crystal
      structure of UHRF1 containing both TTD and PHD (TTD-PHD) in complex with H3K9m3
      peptide at 3.0 A resolution. The structure shows that TTD-PHD binds to the
      H3K9me3 peptide with 1:1 stoichiometry with the two domains connected by the
      H3K9me3 peptide and a linker region. The TTD interacts with residues Arg-8 and
      trimethylated Lys-9, and the PHD interacts with residues Ala-1, Arg-2, and Lys-4
      of the H3K9me3 peptide. The biochemical experiments indicate that PHD-mediated
      recognition of unmodified H3 is independent of the TTD, whereas TTD-mediated
      recognition of H3K9me3 PHD. Thus, both TTD and PHD are essential for specific
      recognition of H3K9me3 by UHRF1. Interestingly, the H3K9me3 peptide induces
      conformational changes of TTD-PHD, which do not affect the autoubiquitination
      activity or hemimethylated DNA binding affinity of UHRF1 in vitro. Taken
      together, our studies provide structural insight into the coordinated recognition
      of H3K9me3 by the TTD and PHD of UHRF1.

PMID- 23161543
TI  - Biphasic regulation of myosin light chain phosphorylation by p21-activated kinase
      modulates intestinal smooth muscle contractility.
AB  - Supraphysiological mechanical stretching in smooth muscle results in decreased
      contractile activity. However, the mechanism is unclear. Previous studies
      indicated that intestinal motility dysfunction after edema development is
      associated with increased smooth muscle stress and decreased myosin light chain
      (MLC) phosphorylation in vivo, providing an ideal model for studying mechanical
      stress-mediated decrease in smooth muscle contraction. Primary human intestinal
      smooth muscle cells (hISMCs) were subjected to either control cyclical stretch
      (CCS) or edema (increasing) cyclical stretch (ECS), mimicking the biophysical
      forces in non-edematous and edematous intestinal smooth muscle in vivo. ECS
      induced significant decreases in phosphorylation of MLC and MLC phosphatase
      targeting subunit (MYPT1) and a significant increase in p21-activated kinase
      (PAK) activity compared with CCS. PAK regulated MLC phosphorylation in an
      activity-dependent biphasic manner. PAK activation increased MLC and MYPT1
      phosphorylation in CCS but decreased MLC and MYPT1 phosphorylation in hISMCs
      subjected to ECS. PAK inhibition had the opposite results. siRNA studies showed
      that PAK1 plays a critical role in regulating MLC phosphorylation in hISMCs. PAK1
      enhanced MLC phosphorylation via phosphorylating MYPT1 on Thr-696, whereas PAK1
      inhibited MLC phosphorylation via decreasing MYPT1 on both Thr-696 and Thr-853.
      Importantly, in vivo data indicated that PAK activity increased in edematous
      tissue, and inhibition of PAK in edematous intestine improved intestinal
      motility. We conclude that PAK1 positively regulates MLC phosphorylation in
      intestinal smooth muscle through increasing inhibitory phosphorylation of MYPT1
      under physiologic conditions, whereas PAK1 negatively regulates MLC
      phosphorylation via inhibiting MYPT1 phosphorylation when PAK activity is
      increased under pathologic conditions.

PMID- 23161544
TI  - Next generation sequencing in predicting gene function in podophyllotoxin
      biosynthesis.
AB  - Podophyllum species are sources of (-)-podophyllotoxin, an aryltetralin lignan
      used for semi-synthesis of various powerful and extensively employed cancer
      treating drugs. Its biosynthetic pathway, however, remains largely unknown, with
      the last unequivocally demonstrated intermediate being (-)-matairesinol. Herein,
      massively parallel sequencing of Podophyllum hexandrum and Podophyllum peltatum
      transcriptomes and subsequent bioinformatics analyses of the corresponding
      assemblies were carried out. Validation of the assembly process was first
      achieved through confirmation of assembled sequences with those of various genes
      previously established as involved in podophyllotoxin biosynthesis as well as
      other candidate biosynthetic pathway genes. This contribution describes
      characterization of two of the latter, namely the cytochrome P450s, CYP719A23
      from P. hexandrum and CYP719A24 from P. peltatum. Both enzymes were capable of
      converting (-)-matairesinol into (-)-pluviatolide by catalyzing methylenedioxy
      bridge formation and did not act on other possible substrates tested.
      Interestingly, the enzymes described herein were highly similar to methylenedioxy
      bridge-forming enzymes from alkaloid biosynthesis, whereas candidates more
      similar to lignan biosynthetic enzymes were catalytically inactive with the
      substrates employed. This overall strategy has thus enabled facile further
      identification of enzymes putatively involved in (-)-podophyllotoxin biosynthesis
      and underscores the deductive power of next generation sequencing and
      bioinformatics to probe and deduce medicinal plant biosynthetic pathways.

PMID- 23161545
TI  - The beta sliding clamp closes around DNA prior to release by the Escherichia coli
      clamp loader gamma complex.
AB  - Escherichia coli gamma complex clamp loader functions to load the beta sliding
      clamp onto sites of DNA replication and repair. The clamp loader uses the energy
      of ATP binding and hydrolysis to drive conformational changes allowing for beta
      binding and opening, DNA binding, and then release of the beta.DNA complex.
      Although much work has been done studying the sliding clamp and clamp loader
      mechanism, kinetic analysis of the events following beta.gamma complex.DNA
      formation is not complete. Using fluorescent clamp closing and release assays, we
      show that beta closing is faster than beta release, indicating that gamma complex
      closes beta before releasing it around DNA. Using a fluorescent ATP hydrolysis
      assay, we show that there is a burst of ATP hydrolysis before beta closing and
      that beta release may be the rate-limiting step in the overall clamp loading
      reaction. The combined use of these fluorescent assays provides a unique
      perspective into the E. coli clamp loader by providing a measure of the relative
      timing of different events in the clamp loading reaction, helping to elucidate
      the complicated clamp loading mechanism.

PMID- 23161546
TI  - The cannabinoid receptor CB1 modulates the signaling properties of the
      lysophosphatidylinositol receptor GPR55.
AB  - The G protein-coupled receptor (GPCR) 55 (GPR55) and the cannabinoid receptor 1
      (CB1R) are co-expressed in many tissues, predominantly in the central nervous
      system. Seven transmembrane spanning (7TM) receptors/GPCRs can form homo- and
      heteromers and initiate distinct signaling pathways. Recently, several synthetic
      CB1 receptor inverse agonists/antagonists, such as SR141716A, AM251, and AM281,
      were reported to activate GPR55. Of these, SR141716A was marketed as a promising
      anti-obesity drug, but was withdrawn from the market because of severe side
      effects. Here, we tested whether GPR55 and CB1 receptors are capable of (i)
      forming heteromers and (ii) whether such heteromers could exhibit novel signaling
      patterns. We show that GPR55 and CB1 receptors alter each others signaling
      properties in human embryonic kidney (HEK293) cells. We demonstrate that the co
      expression of FLAG-CB1 receptors in cells stably expressing HA-GPR55 specifically
      inhibits GPR55-mediated transcription factor activation, such as nuclear factor
      of activated T-cells and serum response element, as well as extracellular signal
      regulated kinases (ERK1/2) activation. GPR55 and CB1 receptors can form
      heteromers, but the internalization of both receptors is not affected. In
      addition, we observe that the presence of GPR55 enhances CB1R-mediated ERK1/2 and
      nuclear factor of activated T-cell activation. Our data provide the first
      evidence that GPR55 can form heteromers with another 7TM/GPCR and that this
      interaction with the CB1 receptor has functional consequences in vitro. The GPR55
      CB1R heteromer may play an important physiological and/or pathophysiological role
      in tissues endogenously co-expressing both receptors.

PMID- 23161547
TI  - Promiscuous dimerization of the growth hormone secretagogue receptor (GHS-R1a)
      attenuates ghrelin-mediated signaling.
AB  - G protein-coupled receptors (GPCRs), such as the ghrelin receptor (GHS-R1a), the
      melanocortin 3 receptor (MC(3)), and the serotonin 2C receptor (5-HT(2C)), are
      well known for their key role in the homeostatic control of food intake and
      energy balance. Ghrelin is the only known gut peptide exerting an orexigenic
      effect and has thus received much attention as an anti-obesity drug target. In
      addition, recent data have revealed a critical role for ghrelin in dopaminergic
      mesolimbic circuits involved in food reward signaling. This study investigates
      the downstream signaling consequences and ligand-mediated co-internalization
      following heterodimerization of the GHS-R1a receptor with the dopamine 1
      receptor, as well as that of the GHS-R1a-MC(3) heterodimer. In addition, a novel
      heterodimer between the GHS-R1a receptor and the 5-HT(2C) receptor was
      identified. Interestingly, dimerization of the GHS-R1a receptor with the unedited
      5-HT(2C)-INI receptor, but not with the partially edited 5-HT(2C)-VSV isoform,
      significantly reduced GHS-R1a agonist-mediated calcium influx, which was
      completely restored following pharmacological blockade of the 5-HT(2C) receptor.
      These results combined suggest a potential novel mechanism for fine-tuning GHS
      R1a receptor-mediated activity via promiscuous dimerization of the GHS-R1a
      receptor with other G protein-coupled receptors involved in appetite regulation
      and food reward. These findings may uncover novel mechanisms of significant
      relevance for the future pharmacological targeting of the GHS-R1a receptor in the
      homeostatic regulation of energy balance and in hedonic appetite signaling, both
      of which play a significant role in the development of obesity.

PMID- 23161548
TI  - Anticoagulant activity of a unique sulfated pyranosic (1->3)-beta-L-arabinan
      through direct interaction with thrombin.
AB  - A highly sulfated 3-linked beta-arabinan (Ab1) with arabinose in the pyranose
      form was obtained from green seaweed Codium vermilara (Bryopsidales). It
      comprised major amounts of units sulfated on C-2 and C-4 and constitutes the
      first polysaccharide of this type isolated in the pure form and fully
      characterized. Ab1 showed anticoagulant activity by global coagulation tests.
      Less sulfated arabinans obtained from the same seaweed have less or no activity.
      Ab1 exerts its activity through direct and indirect (antithrombin- and heparin
      cofactor II-mediated) inhibition of thrombin. Direct thrombin inhibition was
      studied in detail. By native PAGE, it was possible to detect formation of a
      complex between Ab1 and human thrombin (HT). Ab1 binding to HT was measured by
      fluorescence spectroscopy. CD spectra of the Ab1 complex suggested that ligand
      binding induced a small conformational change on HT. Ab1-thrombin interactions
      were studied by molecular dynamic simulations using the persulfated
      octasaccharide as model compound. Most carbohydrate-protein contacts would occur
      by interaction of sulfate groups with basic amino acid residues on the surface of
      the enzyme, more than 60% of them being performed by the exosite 2-composing
      residues. In these interactions, the sulfate groups on C-2 were shown to interact
      more intensely with the thrombin structure. In contrast, the disulfated
      oligosaccharide does not promote major conformational modifications at the
      catalytic site when complexed to exosite 1. These results show that this novel
      pyranosic sulfated arabinan Ab1 exerts its anticoagulant activity by a mechanism
      different from those found previously for other sulfated polysaccharides and
      glycosaminoglycans.

PMID- 23161549
TI  - The voltage-dependent anion channel (VDAC) binds tissue-type plasminogen
      activator and promotes activation of plasminogen on the cell surface.
AB  - The voltage-dependent anion channel (VDAC), a major pore-forming protein in the
      outer membrane of mitochondria, is also found in the plasma membrane of a large
      number of cells where in addition to its role in regulating cellular ATP release
      and volume control it is important for maintaining redox homeostasis. Cell
      surface VDAC is a receptor for plasminogen kringle 5, which promotes partial
      closure of the channel. In this study, we demonstrate that VDAC binds tissue-type
      plasminogen activator (t-PA) on human neuroblastoma SK-N-SH cells. Binding of t
      PA to VDAC induced a decrease in K(m) and an increase in the V(max) for
      activation of its substrate, plasminogen (Pg). This resulted in accelerated Pg
      activation when VDAC, t-PA, and Pg were bound together. VDAC is also a substrate
      for plasmin; hence, it mimics fibrin activity. Binding of t-PA to VDAC occurs
      between a t-PA fibronectin type I finger domain located between amino acids
      Ile(5) and Asn(37) and a VDAC region including amino acids (20)GYGFG(24). These
      VDAC residues correspond to a GXXXG repeat motif commonly found in amyloid beta
      peptides that is necessary for aggregation when these peptides form fibrillar
      deposits on the cell surface. Furthermore, we also show that Pg kringle 5 is a
      substrate for the NADH-dependent reductase activity of VDAC. This ternary complex
      is an efficient proteolytic complex that may facilitate removal of amyloid beta
      peptide deposits from the normal brain and cell debris from injured brain tissue.

PMID- 23161552
TI  - LG3 fragment of endorepellin is a possible biomarker of severity in IgA
      nephropathy.
AB  - IgA nephropathy (IgAN), the most common primary glomerulonephritis, is
      characterized by deposition of IgA in the glomerular mesangium. The diagnosis of
      IgAN still requires a kidney biopsy that cannot easily be repeated in the same
      patient during follow-up. Therefore, identification of noninvasive urinary
      biomarkers would be very useful for monitoring patients with IgAN. We first used
      bidimensional electrophoresis (2DE) coupled to MALDI-TOF-TOF and Western blot to
      identify some urinary biomarkers associated with IgAN. Urine of IgAN patients
      showed an increase of albumin fragments, alpha-1-antitrypsin and alpha-1-beta
      glycoprotein, along with a decrease of a single spot that was identified as the
      laminin G-like 3 (LG3) fragment of endorepellin. The urinary proteomes of 43 IgAN
      patients were compared to those of 30 healthy individuals by ELISA.
      Quantification of LG3 confirmed a significant decrease in the urine of IgAN
      patients compared to healthy controls, except in ten patients in whom LG3 was
      increased. These ten patients had a more severe disease with lower glomerular
      filtration rate values. We found a significant inverse correlation between LG3
      levels and glomerular filtration rate in the 43 patients with IgAN, which was not
      observed in 65 patients with other glomerular diseases including membranous
      nephropathy (23), lupus nephropathy (13), focal segmental glomerulosclerosis
      (15), diabetic nephropathy (14), and six patients with nonglomerular diseases.
      Therefore, we suggest that the LG3 fragment of endorepellin could be associated
      with IgAN severity and might be related to pathogenesis of IgAN.

PMID- 23161550
TI  - Phosphorylation of dopamine transporter serine 7 modulates cocaine analog
      binding.
AB  - As an approach to elucidating dopamine transporter (DAT) phosphorylation
      characteristics, we examined in vitro phosphorylation of a recombinant rat DAT N
      terminal peptide (NDAT) using purified protein kinases. We found that NDAT
      becomes phosphorylated at single distinct sites by protein kinase A (Ser-7) and
      calcium-calmodulin-dependent protein kinase II (Ser-13) and at multiple sites
      (Ser-4, Ser-7, and Ser-13) by protein kinase C (PKC), implicating these residues
      as potential sites of DAT phosphorylation by these kinases. Mapping of rat
      striatal DAT phosphopeptides by two-dimensional thin layer chromatography
      revealed basal and PKC-stimulated phosphorylation of the same peptide fragments
      and comigration of PKC-stimulated phosphopeptide fragments with NDAT Ser-7
      phosphopeptide markers. We further confirmed by site-directed mutagenesis and
      mass spectrometry that Ser-7 is a site for PKC-stimulated phosphorylation in
      heterologously expressed rat and human DATs. Mutation of Ser-7 and nearby
      residues strongly reduced the affinity of rat DAT for the cocaine analog (-)
      2beta-carbomethoxy-3beta-(4-fluorophenyl) tropane (CFT), whereas in rat striatal
      tissue, conditions that promote DAT phosphorylation caused increased CFT
      affinity. Ser-7 mutation also affected zinc modulation of CFT binding, with Ala
      and Asp substitutions inducing opposing effects. These results identify Ser-7 as
      a major site for basal and PKC-stimulated phosphorylation of native and expressed
      DAT and suggest that Ser-7 phosphorylation modulates transporter conformational
      equilibria, shifting the transporter between high and low affinity cocaine
      binding states.

PMID- 23161551
TI  - Zebrafish as a model for monocarboxyl transporter 8-deficiency.
AB  - Allan-Herndon-Dudley syndrome (AHDS) is a severe psychomotor retardation
      characterized by neurological impairment and abnormal thyroid hormone (TH)
      levels. Mutations in the TH transporter, monocarboxylate transporter 8 (MCT8),
      are associated with AHDS. MCT8 knock-out mice exhibit impaired TH levels;
      however, they lack neurological defects. Here, the zebrafish mct8 gene and
      promoter were isolated, and mct8 promoter-driven transgenic lines were used to
      show that, similar to humans, mct8 is primarily expressed in the nervous and
      vascular systems. Morpholino-based knockdown and rescue experiments revealed that
      MCT8 is strictly required for neural development in the brain and spinal cord.
      This study shows that MCT8 is a crucial regulator during embryonic development
      and establishes the first vertebrate model for MCT8 deficiency that exhibits a
      neurological phenotype.

PMID- 23161553
TI  - Carbon nanorings and their enhanced lithium storage properties.

PMID- 23161555
TI  - Combining spectroscopy and theory to evaluate structural models of
      metalloenzymes: a case study on the soluble [NiFe] hydrogenase from Ralstonia
      eutropha.
AB  - Hydrogenases catalyse the reversible cleavage of molecular hydrogen into protons
      and electrons. While most of these enzymes are inhibited under aerobic
      conditions, some hydrogenases are catalytically active even at ambient oxygen
      levels. In particular, the soluble [NiFe] hydrogenase from Ralstonia eutropha H16
      couples reversible hydrogen cycling to the redox conversion of NAD(H). Its
      insensitivity towards oxygen has been formerly ascribed to the putative presence
      of additional cyanide ligands at the active site, which has been, however,
      discussed controversially. Based on quantum chemical calculations of model
      compounds, we demonstrate that spectroscopic consequences of the proposed non
      standard set of inorganic ligands are in contradiction to the underlying
      experimental findings. In this way, the previous model for structure and function
      of this soluble hydrogenase is disproved on a fundamental level, thereby
      highlighting the efficiency of computational methods for the evaluation of
      experimentally derived mechanistic proposals.

PMID- 23161556
TI  - Study of peripheral BRAF(V600E) mutation as a possible novel marker for papillary
      thyroid carcinomas.
AB  - BACKGROUND: The BRAF(V600E) mutation can be detected peripherally in the serum of
      patients with thyroid cancer. The purpose of this study was to establish the
      value of detecting the peripheral BRAF(V600E) mutation as a serum tumor marker in
      this population. METHODS: In this study, we obtained 94 serum samples from
      patients with papillary thyroid cancer positive for the BRAF(V600E) mutation in
      the tumor itself. The serum samples were analyzed for BRAF(V600E) mutation using
      real-time polymerase chain reaction (PCR). RESULTS: Sixty-seven patients (71.3%)
      had papillary thyroid microcarcinoma and 26 patients (27.7%) had underlying
      lymphocytic thyroiditis. Forty-three patients (45.7%) were found to have stage
      III or stage IV thyroid cancer. None of the patients had a detectable serum
      BRAF(V600E) mutation. CONCLUSION: We were unable to identify peripheral
      BRAF(V600E) mutations in patients with papillary thyroid cancer using real-time
      PCR. Further studies will be needed to validate our results using various
      diagnostic methods.

PMID- 23161554
TI  - SILAC-based quantitative proteomic analysis of gastric cancer secretome.
AB  - PURPOSE: Gastric cancer is a commonly occurring cancer in Asia and one of the
      leading causes of cancer deaths. However, there is no reliable blood-based
      screening test for this cancer. Identifying proteins secreted from tumor cells
      could lead to the discovery of clinically useful biomarkers for early detection
      of gastric cancer. EXPERIMENTAL DESIGN: A SILAC-based quantitative proteomic
      approach was employed to identify secreted proteins that were differentially
      expressed between neoplastic and non-neoplastic gastric epithelial cells.
      Proteins from the secretome were subjected to SDS-PAGE and SCX-based
      fractionation, followed by mass spectrometric analysis on an LTQ-Orbitrap Velos
      mass spectrometer. Immunohistochemical labeling was employed to validate a subset
      of candidates using tissue microarrays. RESULTS: We identified 2205 proteins in
      the gastric cancer secretome of which 263 proteins were overexpressed greater
      than fourfold in gastric cancer-derived cell lines as compared to non-neoplastic
      gastric epithelial cells. Three candidate proteins, proprotein convertase
      subtilisin/kexin type 9 (PCSK9), lectin mannose binding 2 (LMAN2), and PDGFA
      associated protein 1 (PDAP1) were validated by immunohistochemical labeling.
      CONCLUSIONS AND CLINICAL RELEVANCE: We report here the largest cancer secretome
      described to date. The novel biomarkers identified in the current study are
      excellent candidates for further testing as early detection biomarkers for
      gastric adenocarcinoma.

PMID- 23161557
TI  - Effects of platelet-rich plasma-containing fragmin/protamine microparticles in
      enhancing endothelial and smooth muscle cell growth and inducing collateral
      vessels in a rabbit model of hindlimb ischemia.
AB  - The purpose of the study was to evaluate the effects of isogenous platelet-rich
      plasma (PRP)-containing fragmin/protamine microparticles (F/P MPs) as a delivery
      system for proteins in PRP on growth of endothelial and smooth muscle cells
      (SMCs) in vitro and as an alternative treatment for peripheral arterial disease
      (PAD) and critical limb ischemia. Frozen and thawed PRP contains high
      concentrations of growth factors that are adsorbed by F/P MPs. Human aorta
      endothelial cells (AECs) and SMCs were grown in a medium with PRP. Addition of
      F/P MPs significantly enhanced the proliferative effects of PRP on AECs and SMCs
      at 37  degrees C for >10 days. Intramuscular administration of phosphate-buffered
      saline (PBS; 2 mL, control), F/P MPs (12 mg in 2 mL PBS), PRP (2 mL), or PRP (2
      mL) containing F/P MPs (12 mg) was then performed in a rabbit model of hindlimb
      ischemia prepared by resection of the left femoral artery. Blood flow and
      pressure were measured on days 0, 14, and 28, and angiography to assess
      arteriogenesis was performed on day 28. PRP-containing F/P MPs strongly induced
      functional collateral vessels in the rabbit model of hindlimb ischemia,
      indicating possible use of these microparticles in therapy for PAD.

PMID- 23161558
TI  - In-depth proteomic analysis of banana (Musa spp.) fruit with combinatorial
      peptide ligand libraries.
AB  - Musa ssp. is among the world's leading fruit crops. Although a strong interest on
      banana biochemistry exists in the scientific community, focused on metabolite
      composition, proteins have been scarcely investigated even if they play an
      important role in food allergy and stability, are a source of biologically active
      peptides, and can provide information about nutritional aspects of this fruit. In
      this work we have employed the combinatorial peptide ligand libraries after
      different types of protein extractions, for searching the very low-abundance
      proteins in banana. The use of advanced MS techniques and Musa ssp. mRNAs
      database in combination with the Uniprot_viridiplantae database allowed us to
      identify 1131 proteins. Among this huge amount of proteins we found several
      already known allergens such as Mus a 1, pectinesterase, superoxide dismutase,
      and potentially new allergens. Additionally several enzymes involved in
      degradation of starch granules and strictly correlated to ripening stage were
      identified. This is the first in-depth exploration of the banana fruit proteome
      and one of the largest descriptions of the proteome of any vegetable system.

PMID- 23161559
TI  - Imaging mass spectrometry and genome mining reveal highly antifungal virulence
      factor of mushroom soft rot pathogen.
AB  - Caught in the act: imaging mass spectrometry of a button mushroom infected with
      the soft rot pathogen Janthinobacterium agaricidamnosum in conjunction with
      genome mining revealed jagaricin as a highly antifungal virulence factor that is
      not produced under standard cultivation conditions. The structure of jagaricin
      was rigorously elucidated by a combination of physicochemical analyses, chemical
      derivatization, and bioinformatics.

PMID- 23161560
TI  - Quantitative biomarkers of human skin photoaging based on intrinsic second
      harmonic generation signal.
AB  - Collagen change is a major feature in the photoaged human skin. Here, we present
      the use of intrinsic second harmonic generation (SHG) signal as a novel means to
      quantify collagen change with photoaging. We obtain the SHG images of the
      superficial dermis from ex vivo the cheek skin and the abdomen skin of eight
      patients aged 55-60 years. The results show that SHG signal can quantitatively
      reveal collagen change between normal and photoaged human skin in three
      dimensions. By comparing normal with photoaged dermis, there are significant
      differences in the collagen content and fine structure, providing substantial
      potential to be applied in vivo for the clinical diagnosis of human skin
      photoaging.

PMID- 23161561
TI  - A method for assessing causation of field exposure-response relationships.
AB  - Because associations between agents and environmental effects are not necessarily
      causal, it is necessary to assess causation before using such relationships in
      environmental management. The authors adapted epidemiological methods to assess
      general causal hypotheses. General causation establishes that an agent is capable
      of causing an effect. The method uses all relevant and good-quality evidence in a
      weight-of-evidence system. The system is credible due to its explicit a priori
      criteria. The evidence is organized in terms of six characteristics of causation:
      co-occurrence, preceding causation, interaction, alteration, sufficiency, and
      time order. The causal assessment proceeds through six steps that generate,
      organize, and score evidence to determine whether causation is adequately
      supported by the body of evidence.

PMID- 23161562
TI  - Self-harm is common in adolescents in England.

PMID- 23161563
TI  - Similar benefits with dialectical behaviour therapy or general psychiatric
      management for people with borderline personality disorder.

PMID- 23161564
TI  - The DAISY psychosocial intervention does not improve outcomes in patients with
      mild Alzheimer's disease or their carers.

PMID- 23161565
TI  - Study on the effects of electrolytes and solvents in the determination of
      quaternary ammonium ions by nonaqueous capillary electrophoresis with contactless
      conductivity detection.
AB  - A study on the separation of lipophilic quaternary ammonium cations in NACE
      coupled with contactless conductivity detection (NACE-C(4)D) is presented. The
      suitability of different salts dissolved in various organic solvents as running
      electrolytes in NACE-C(4)D was investigated. A solvent mixture of
      methanol/acetonitrile at a ratio of 90%:10% v/v showed the best results.
      Deoxycholic acid sodium salt as BGE was found to provide exceptional high
      stability with low baseline noise that leads to highest S/N ratios for the target
      analytes among all BGEs tested. Under the optimum conditions, capillaries with
      different internal diameters were examined and an id of 50 MUm was found to give
      best detection sensitivity. The proposed method was validated and showed good
      linearity in the range from 2.5 to 200 MUM, low limits of detection (0.1-0.7 MUM)
      and acceptable reproducibility of peak area (intraday RSD 0.1-0.7%, n = 3;
      interday RSD 5.9-9.4%, n = 3).

PMID- 23161566
TI  - Epithelial-to-mesenchymal transition of human lung alveolar epithelial cells in a
      microfluidic gradient device.
AB  - Epithelial-to-mesenchymal transition (EMT), a process in which epithelial cells
      undergo phenotypic transitions to fibrotic cells, is induced by stimulants
      including transforming growth factor-beta1 (TGF-beta1). In the present study, we
      developed a microfluidic gradient device to reproduce EMT in A549 human lung
      alveolar epithelial cells in response to TGF-beta1 gradients. The device was
      directly mounted on the cells that had grown in cell culture plates and produced
      a stable concentration gradient of TGF-beta1 with negligible shear stress,
      thereby providing a favorable environment for the anchorage-dependent cells. A549
      cells elongated with the characteristic spindle-shaped morphological changes with
      upregulation of alpha-smooth muscle actin, a mesenchyme marker, in a gradient
      dependent manner, suggestive of EMT progression. We observed that at higher TGF
      beta1 concentrations ranging from 5 to 10 ng/mL, the cultures in the microfluidic
      device allowed to quantitatively pick up subtle differences in the EMT cellular
      response as compared with plate cultures. These results suggest that the
      microfluidic gradient device would accurately determine the optimal
      concentrations of TGF-beta1, given that epithelial cells of different tissue
      origins greatly vary their responses to TGF-beta1. Therefore, this microfluidic
      device could be a powerful tool to monitor EMT induced by a variety of
      environmental stresses including cigarette smoke with high sensitivity.

PMID- 23161567
TI  - Salvage chemoimmunotherapy with rituximab, ifosfamide and etoposide (R-IE
      regimen) in patients with primary CNS lymphoma relapsed or refractory to high
      dose methotrexate-based chemotherapy.
AB  - Despite a high proportion of patients with primary CNS lymphoma (PCNSL)
      experiences failure after/during first-line treatment, a few studies focused on
      salvage therapy are available, often with disappointing results. Herein, we
      report feasibility and activity of a combination of rituximab, ifosfamide and
      etoposide (R-IE regimen) in a multicentre series of patients with PCNSL relapsed
      or refractory to high-dose methotrexate-based chemotherapy. We considered
      consecutive HIV-negative patients <=75 years old with failed PCNSL treated with R
      IE regimen (rituximab 375 mg/m(2) , day 0; ifosfamide 2 g/m(2) /day, days1-3;
      etoposide 250 mg/m(2) , day 1; four courses). Twenty-two patients (median age 60
      years; range 39-72; male/female ratio: 1:4) received R-IE as second-line (n = 18)
      or third-line (n = 4) treatment. Eleven patients had refractory PCNSL, and 11 had
      relapsing disease. Twelve patients had been previously irradiated. Sixty (68%) of
      the 88 planned courses were actually delivered; only one patient interrupted R-IE
      because of toxicity. Grade 4 hematological toxicity was manageable; a single case
      of grade 4 non-hematological toxicity (transient hepatotoxicity) was recorded.
      Response was complete in six patients and partial in three (overall response rate
      = 41%; 95%CI: 21-61%). Seven patients were successfully referred to autologous
      peripheral blood stem cell collection; four responders were consolidated with
      high-dose chemotherapy supported by autologous stem cell transplant. At a median
      follow-up of 24 months, eight responders did not experience relapse, two of them
      died of neurological impairment while in remission. Six patients are alive, with
      a 2-year survival after relapse of 25 +/- 9%. We concluded that R-IE is a
      feasible and active combination for patients with relapsed/refractory PCNSL. This
      regimen allows stem cell collection and successful consolidation with high-dose
      chemotherapy and autologous transplant.

PMID- 23161569
TI  - Photocatalytic overall water splitting promoted by an alpha-beta phase junction
      on Ga2O3.
AB  - When Alpha met Beta: a tuneable alpha-beta surface phase junction on Ga(2)O(3)
      can significantly improve photocatalytic overall water splitting into H(2) and
      O(2) over individual alpha-Ga(2)O(3) or beta-Ga(2)O(3) surface phases. This
      enhanced photocatalytic performance is mainly attributed to the efficient charge
      separation and transfer across the alpha-beta phase junction.

PMID- 23161568
TI  - The critical role of mast cell-derived hypoxia-inducible factor-1alpha in human
      and mice melanoma growth.
AB  - Mast cells play an important role in tumorigenesis. Histamine released from mast
      cells stimulates new vessel formation by acting through the histamine1 (H1)
      receptor. Despite the evidence of the role of mast cells in tumor growth and
      angiogenesis, the potential mechanism remains to be elucidated. Therefore, we
      investigated the role of mast cell-derived HIF-1alpha in melanoma growth. Here,
      we identify that the most positive cells for HIF-1alpha staining are seen in mast
      cells of human and animal melanoma tissue. The number of the stromal cell types
      (fibroblasts, macrophages and endothelial cells) was also increased in melanoma
      tissues. In activated bone marrow-derived mast cells (BMMCs), expressions of HIF
      1alpha and VEGF were increased. Histamine also induced the expressions of HIF
      1alpha and VEGF in BMMCs. H1 receptor antagonists significantly improved overall
      survival rates and substantially suppressed tumor growth as well as the
      infiltration of mast cells and levels of VEGF through the inhibition of HIF
      1alpha expression in B16F10 melanoma-bearing mice. Furthermore, the injection of
      HIF-1alpha depleted BMMCs markedly inhibited the growth of tumors and migration
      of mast cells and increased the survival rate of the mice. These findings
      emphasize that the growth of melanoma can actually be exacerbated by mast cell
      derived HIF-1alpha. In aggregate, our results reveal a novel role for mast cell
      derived HIF-1alpha in the melanoma microenvironment and have important
      implications for the design of therapeutic strategies.

PMID- 23161570
TI  - Abstracts of the 2012 Advances in Inflammatory Bowel Diseases Crohn's & Colitis
      Foundation's National Clinical & Research Conference. December 13-15, 2012.
      Hollywood, Florida, USA.

PMID- 23161571
TI  - Cofilin, a hypoxia-regulated protein in murine lungs identified by 2DE: role of
      the cytoskeletal protein cofilin in pulmonary hypertension.
AB  - Chronic alveolar hypoxia induces vascular remodeling processes in the lung
      resulting in pulmonary hypertension (PH). However, the mechanisms underlying
      pulmonary remodeling processes are not fully resolved yet. To investigate
      functional changes occurring during hypoxia exposure we applied 2DE to compare
      protein expression in lungs from mice subjected to 3 h of alveolar hypoxia and
      those kept under normoxic conditions. Already after this short-time period
      several proteins were significantly regulated. Subsequent analysis by MALDI-MS
      identified cofilin as one of the most prominently upregulated proteins. The
      regulation was confirmed by western blotting and its cellular localization was
      determined by immunohisto- and immunocytochemistry. Interestingly, enhanced
      cofilin serine 3 phosphorylation was observed after short-term and after chronic
      hypoxia-induced PH in mice, in pulmonary arterial smooth muscle cells (PASMC)
      from monocrotaline-induced PH in rats, in lungs of idiopathic pulmonary arterial
      hypertension patients and in hypoxic or platelet-derived growth factor BB-treated
      human PASMC. Furthermore, elevated cofilin phosphorylation was attenuated by
      curative treatment of monocrotaline-induced PH in rats and hypoxia-induced PH in
      mice with the PDGF-BB receptor antagonist imatinib. In conclusion, short-term
      hypoxic exposure induced prominent changes in lung protein regulation. These very
      early changes allowed us to identify potential triggers of PH. Thus, respective
      2DE analysis can lead to the identification of new target proteins for the
      possible treatment of PH.

PMID- 23161573
TI  - Stat5 in breast cancer: potential oncogenic activity coincides with positive
      prognosis for the disease.
AB  - Nuclear localization of signal transducer and activator of transcription (Stat) 5
      marks good prognosis in estrogen receptor/progesterone receptor-positive breast
      tumors. This positive characteristic is counteracted by studies in laboratory
      animals demonstrating that deregulated Stat5 activity may convert proper mammary
      development into a latent oncogenic process. Tumorigenesis is initiated during
      the parity cycles, most probably during pregnancy, when the activated Stat5
      antagonizes or manipulates parity's protective mechanisms. For example, it can
      alter the differentiation/proliferation balance, induce growth hormone signaling,
      cause specific alteration in chromatin structure, inhibit tumor-suppressor
      activity and induce DNA damage that counteracts the enhanced DNA-damage response
      exerted by parity. Palpable tumors develop after a latent period from individual
      cells. This happens in the estropausal period in transgenic mice maintaining
      deregulated Stat5 activity in the mammary gland, or during involution, months
      after transplantation of transfected cells with constitutively active Stat5.
      Candidate vulnerable cells are those which maintain high nuclear Stat5 activity.
      Due to the hazardous outcome of deregulated Stat5 activity in these cells, such
      as induced DNA damage or high cyclin D1 activity, the gland is prone to
      transformation. The developing tumors are mostly adenocarcinomas or their
      subtypes. They are estrogen receptor-positive and maintain a specific Stat5 gene
      signature that allows tracking their inducer. From a clinical point of view,
      deregulated Stat5 activity represents a genuine risk factor for breast cancer.
      Monitoring Stat5 activity during vulnerable periods and developing specific tools
      for its suppression in breast epithelial cells could potentially limit new
      incidence of the disease.

PMID- 23161574
TI  - The pharmacologic inhibition of the xc- antioxidant system improves the antitumor
      efficacy of COX inhibitors in the in vivo model of 3-MCA tumorigenesis.
AB  - The chemopreventive and therapeutic efficacy of the cyclooxygenase (COX)
      inhibitor ibuprofen (IB) and of sulfasalazine (SASP), a drug that targets the
      antioxidant xc- system, were exploited in the experimental model of 3
      methylcholantrene (3-MCA)-induced mouse sarcoma. The chemopreventive treatments
      gave unsatisfactory results because administration of IB one day after the 3-MCA
      injection only slightly delayed the tumor development, whereas SASP dispensed
      under the same conditions resulted in accelerated tumorigenesis. Similarly, the
      therapeutic treatment with either drug, administrated daily from the tumor
      detection, decreased the proliferation rate of tumor cells and increased the
      survival of treated mice only at a low extent. Remarkably, the combined
      chemopreventive treatment with IB and therapeutic treatment with SASP displayed a
      better efficacy, with strong delay of sarcoma growth, reduced tumor size and
      increased survival of treated mice. The two drugs target not only tumor cells but
      also tumor-associated macrophages that were dramatically decreased in the tumor
      infiltrate of mice subjected to the combined treatment. The synergistic effects
      of the association between a broad anti-inflammatory compound, such as IB, and a
      redox-directed drug, such as SASP, shed new light in the role of inflammation and
      of the redox response in chemical tumorigenesis and point to the combined
      chemopreventive plus therapeutic treatment with IB and SASP as a promising novel
      approach for antitumor therapy.

PMID- 23161572
TI  - BMP2/BMP4 colorectal cancer susceptibility loci in northern and southern European
      populations.
AB  - Genome-wide association studies have successfully identified 20 colorectal cancer
      susceptibility loci. Amongst these, four of the signals are defined by tagging
      single nucleotide polymorphisms (SNPs) on regions 14q22.2 (rs4444235 and
      rs1957636) and 20p12.3 (rs961253 and rs4813802). These markers are located close
      to two of the genes involved in bone morphogenetic protein (BMP) signaling (BMP4
      and BMP2, respectively). By investigating these four SNPs in an initial cohort of
      Spanish origin, we found substantial evidence that minor allele frequencies
      (MAFs) may be different in northern and southern European populations. Therefore,
      we genotyped three additional southern European cohorts comprising a total of
      2028 cases and 4273 controls. The meta-analysis results show that only one of the
      association signals (rs961253) is effectively replicated in the southern European
      populations, despite adequate power to detect all four. The other three SNPs
      (rs4444235, rs1957636 and rs4813802) presented discordant results in MAFs and
      linkage disequilibrium patterns between northern and southern European cohorts.
      We hypothesize that this lack of replication could be the result of differential
      tagging of the functional variant in both sets of populations. Were this true, it
      would have complex consequences in both our ability to understand the nature of
      the real causative variants, as well as for further study designs.

PMID- 23161575
TI  - Surgical treatment for aortic periannular abscess/pseudoaneurysm caused by
      infective endocarditis.
AB  - Delayed diagnosis or surgery sometimes causes more extensive destruction of
      aortic periannular abscess, or pseudoaneurysm, resulting in left ventricular
      aortic discontinuity, particularly in patients with prosthetic valve
      endocarditis. The condition complicates the surgical procedures and causes
      worsening of short- and long-term outcomes. In-hospital mortality in patients
      with prosthetic valve endocarditis has been reported to be as high as 15-20 %,
      even at leading hospitals in the world. Contemporary modes of surgery for
      periannular abscess/pseudoaneurysm involve drainage of the cavity, radical
      debridement of necrotic tissue, annular reconstruction of the destroyed annulus,
      and root replacement using an optimal conduit. Radical debridement is of primary
      importance and is the universally accepted procedure, which frequently requires
      annular reconstruction using a pericardial patch. Conventional aortic valve
      replacement using a mechanical or stented biological valve, aortic valve
      replacement with translocation, aortic root replacement using an allograft,
      pulmonary autograft (Ross procedure), stentless biological valve, or a composite
      graft are conduits of choice. All things considered, allograft is believed to be
      the best conduit for a destroyed annulus because of better fit and its resistance
      to infection; however, recent reports have failed to confirm the superiority of
      allograft over other conduits in terms of long-term survival and freedom from
      reoperation/recurrence of infection. Short- and long-term outcomes have been
      studies for every type of conduit, but the selection of conduits for aortic root
      replacement is still controversial.

PMID- 23161576
TI  - Prognostic utility of autoantibodies to alpha-enolase and Hsp70 for cancer of the
      gingivo-buccal complex using immunoproteomics.
AB  - PURPOSE: Studies from our laboratory have reported 14 tumor antigens that elicit
      an autoantibody response in patients with cancer of the gingivobuccal complex
      (GBC) In this study, utility of the autoantibody response has been evaluated for
      prognosis of cancer of the GBC. EXPERIMENTAL DESIGN: Autoantibody response was
      evaluated using immunoproteomics and the prognostic significance was assessed by
      Kaplan-Meier survival and multivariate analysis. RESULTS: Autoantibody response
      against alpha-enolase isoforms a, b, and c and Hsp70 was detected in 27, 53, 64,
      and 26% of the 78 patients, respectively. Patients positive for autoantibody
      response to alpha-ENO and Hsp70 individually and in combination, showed
      significantly reduced disease-free survival (DFS) compared to those who do not
      show autoantibody response to either of them. Further the patients, who exhibit
      autoantibody response to alpha-ENO and Hsp70 in combination with nodal
      involvement and/or differentiation status, have significantly lowered DFS. The
      relative risk of recurrence is 3.41 for patients who exhibit autoantibody
      response to both the antigens. CONCLUSIONS AND CLINICAL RELEVANCE: Autoantibody
      response against alpha-ENO and Hsp70 provides an additional parameter and may be
      utilized along with nodal involvement and differentiation status for better
      prognosis of cancer of GBC.

PMID- 23161577
TI  - Successful treatment of severe thrombocytopenia with romiplostim in a pregnant
      patient with systemic lupus erythematosus.
AB  - We present a case of a pregnant woman at 27 weeks of gestation with systemic
      lupus erythematosus who developed severe thrombocytopenia presenting with melena,
      epistaxis, gum bleeding and frank hematuria. She was resistant to most treatment
      modalities, including steroids, intravenous immunoglobulins (IVIG), rituximab, IV
      cyclophosphamide and eltrombopag. She responded to romiplostim with normalization
      of her platelet count, which enabled her to be delivered safely at 34 weeks of
      gestation.

PMID- 23161578
TI  - The use of electroconvulsive therapy in a patient with juvenile systemic lupus
      erythematosus and catatonia.
AB  - Catatonia is a rare manifestation in patients with systemic lupus erythematosus
      (SLE). As catatonia can be associated with both psychiatric and organic
      conditions, this could create a diagnostic dilemma once this occurs in SLE
      patients. The report describes a 15-year-old female with SLE who developed
      catatonia three days after the diagnosis of SLE was made. Her catatonia was
      refractory to the treatment with immunosuppressive therapy, which included pulse
      methylprednisolone, intravenous cyclophosphamide, rituximab, intravenous
      immunoglobulin (IVIG) and plasmapheresis. Given her persistent catatonia,
      electroconvulsive therapy (ECT) was initiated three months after the onset of her
      symptoms. After the third ECT treatment, her mental status dramatically improved
      and returned nearly to baseline while she was continued on the immunosuppression.
      This is the first report of a successful ECT therapy in catatonic lupus in
      children.

PMID- 23161579
TI  - Neonatal lupus complicated by hemorrhagic stroke.
AB  - Neonatal lupus is a passively acquired autoimmune syndrome resulting from the
      transplacental passage of maternal anti-Ro/SSA and/or anti-La/SSB antibodies to
      the fetus. Few past studies have reported central nervous system involvement in
      neonatal lupus, and most cases had a good neurological outcome. We report here a
      preterm case of neonatal lupus with thrombocytopenia and comorbid hemorrhagic
      stroke. In the follow-up, the infant developed spastic quadriplegia and showed
      delayed milestones. We believe that this is the first reported case of neonatal
      lupus accompanied by perinatal hemorrhagic stroke. We present this case to remind
      clinicians to conduct regular central nervous system surveys in cases of neonatal
      lupus.

PMID- 23161581
TI  - Influence of silver doping on electron transport in thin films of PbSe
      nanocrystals.
AB  - Field-effect transistors are fabricated from thin films of Ag-doped PbSe
      nanocrystals to analyze the influence of electronically active impurities on
      electrical transport in this important material for nanocrystal applications.
      Data is collected as a function of nanocrystal size, dopant concentration, and
      temperature. Changes in the Fermi level and transport parameters indicate that Ag
      is acting as a p-type dopant (acceptor).

PMID- 23161580
TI  - SILAC-based proteomic analysis to investigate the impact of amyloid precursor
      protein expression in neuronal-like B103 cells.
AB  - Alzheimer's disease (AD) is the most prevalent form of dementia in the elderly.
      Amyloid plaque formation through aggregation of the amyloid beta peptide derived
      from amyloid precursor protein (APP) is considered one of the hallmark processes
      leading to AD pathology; however, the precise role of APP in plaque formation and
      AD pathogenesis is yet to be determined. Using stable isotope labeling by amino
      acids in cell culture (SILAC) and MS, protein expression profiles of APP null,
      rat neuronal-like B103 cells were compared to B103-695 cells that express the APP
      isoform, APP-695. A total of 2979 unique protein groups were identified among
      three biological replicates and significant protein expression changes were
      identified in a total of 102 nonredundant proteins. Some of the top biological
      functions associated with the differentially expressed proteins identified
      include cellular assembly, organization and morphology, cell cycle, lipid
      metabolism, protein folding, and PTMs. We report several novel biological
      pathways influenced by APP-695 expression in neuronal-like cells and provide
      additional framework for investigating altered molecular mechanisms associated
      with APP expression and processing and contribution to AD pathology.

PMID- 23161583
TI  - Hepatitis B virus DNA in patients with HBsAg in south western Nigeria.
AB  - There are about 400 million people with chronic hepatitis B virus (HBV) infection
      worldwide with a potential of adverse sequelae including hepatocellular
      carcinoma. Recent data have shown that the level of HBV DNA in serum or plasma of
      an infected person probably reflects more accurately the replicative activity of
      the virus and therefore may serve as a better maker for management of the
      infection. This study was designed to determine the rate of detection of HBV DNA
      in blood samples of patients with HBsAg positive in Nigeria in comparison with
      the HBe and anti-HBe used widely as serological markers of infectivity. Plasma
      samples from 105 patients with HBsAg positive were tested for the presence of
      HBeAg and anti-HBe using a commercial enzyme-linked immunosorbent assay while
      plasma HBV DNA was quantified using the COBAS Amplicor HBV Monitor assay. Of the
      105 HBsAg samples, 17 (16.2%) and 85 (81%) were positive for HBeAg and anti-HBe,
      respectively, while 8 (7.6%) were negative for both HBeAg and anti-HBe. HBV DNA
      was detected in 86 (81.9%) of the samples, out of which 15 (18.1%) and 67 (80.7%)
      were positive for HBeAg and anti-HBe, respectively. HBV DNA was detected in 78.4%
      of the HBeAg negative samples and in all the eight samples that were negative for
      both HBeAg and anti-HBe. The implication of these findings in the management of
      patients with HBV infection is compelling.

PMID- 23161582
TI  - PA1 protein, a new competitive decelerator acting at more than one step to impede
      glucocorticoid receptor-mediated transactivation.
AB  - Numerous cofactors modulate the gene regulatory activity of glucocorticoid
      receptors (GRs) by affecting one or more of the following three major
      transcriptional properties: the maximal activity of agonists (A(max)), the
      potency of agonists (EC(50)), and the partial agonist activity of antisteroids
      (PAA). Here, we report that the recently described nuclear protein, Pax2
      transactivation domain interaction protein (PTIP)-associated protein 1 (PA1), is
      a new inhibitor of GR transactivation. PA1 suppresses A(max), increases the
      EC(50), and reduces the PAA of an exogenous reporter gene in a manner that is
      independent of associated PTIP. PA1 is fully active with, and strongly binds to,
      the C-terminal half of GR. PA1 reverses the effects of the coactivator TIF2 on GR
      mediated gene induction but is unable to augment the actions of the corepressor
      SMRT. Analysis of competition assays between PA1 and TIF2 with an exogenous
      reporter indicates that the kinetic definition of PA1 action is a competitive
      decelerator at two sites upstream from where TIF2 acts. With the endogenous genes
      IGFBP1 and IP6K3, PA1 also represses GR induction, increases the EC(50), and
      decreases the PAA. ChIP and re-ChIP experiments indicate that PA1 accomplishes
      this inhibition of the two genes via different mechanisms as follows: PA1 appears
      to increase GR dissociation from and reduce GR transactivation at the IGFBP1
      promoter regions but blocks GR binding to the IP6K3 promoter. We conclude that
      PA1 is a new competitive decelerator of GR transactivation and can act at more
      than one molecularly defined step in a manner that depends upon the specific
      gene.

PMID- 23161584
TI  - Application of multiple geochemical markers to investigate organic pollution in a
      dynamic coastal zone.
AB  - Multiple geochemical markers, including aliphatic hydrocarbons (n-alkanes),
      linear alkylbenzenes (LABs), and polycyclic aromatic hydrocarbons (PAHs), were
      employed to relate sediment organic chemical pollution in the coastal zone off
      South China to socioeconomic development there. Concentrations of Sigman-C(15-35)
      (n-alkanes with 15-35 carbon atoms), SigmaLAB (sum of C(10) to C(13) LABs), and
      Sigma(26) PAH (sum of 26 PAH compounds) ranged from 110 to 3,160, 11 to 160, and
      26 to 600 ng/g, with medians of 730, 40, and 230 ng/g, respectively. Natural
      hydrocarbons were mainly derived from terrestrial higher plant waxes, and in
      minor amounts from aquatic plankton and bacteria. Compositions of LABs indicated
      that considerable amounts of poorly treated wastewater had been directly
      discharged or transported to the eastern and western coastal areas of Guangdong
      Province. In addition, anthropogenic hydrocarbons were derived largely from
      vehicular emissions and combustion of domestic coal and biomass and to a lesser
      extent from oil spills. Eastern and western coastal sediments contained higher
      levels of LABs but lower levels of PAHs than those of the Pearl River Estuary, a
      coastal area of the Pearl River Delta. This spatial pattern of organic pollution
      was consistent with chemical use patterns. The eastern and western regions of
      Guangdong Province are economically less developed than the Pearl River Delta
      region, where more domestic wastewater treatment plants have been built. However,
      greater amounts of energy are consumed in the latter region to produce more
      combustion-derived PAH contamination.

PMID- 23161585
TI  - The impact of the National Essential Medicines Policy on prescribing behaviours
      in primary care facilities in Hubei province of China.
AB  - AIM: To assess the impact of the National Essential Medicines Policy (NEMP) on
      the use of medicines in government-owned primary care institutions in Hubei
      province of China. STUDY DESIGN: Quasi-experimental design and time-trend
      analysis. METHODS: A systematic random sampling strategy was employed to select
      55,800 prescriptions from 18 primary care organizations who progressively
      implemented the NEMP from January 2009 to July 2011. We examined the change of
      patterns of prescriptions. The facilities that implemented the NEMP at a later
      stage served as control. RESULTS: An immediate increased uptake of essential
      medicines of all drugs prescribed which ultimately neared 95%. In total, 38,151
      prescriptions (68%) involved antibiotics, and we found no evidence of reduction
      after the NEMP interventions. A high percentage (59-66%) of prescription drugs
      were administered through parenteral routes and no reduction was found after the
      NEMP interventions. Although the average number of medicines per prescription
      remained unchanged (nearly four), the average cost per prescription declined
      significantly after the NEMP interventions (Y 44.67 vs Y 26.67 CNY, P < 0.03).
      CONCLUSIONS: The NEMP interventions reduced the average cost per prescription;
      however, the irrational use of antibiotics and unnecessary parenteral
      administration remains prevalent. The goals of the NEMP are partially achieved;
      we therefore recommend a strategic approach involving all stakeholders to
      comprehensively achieve all aspirations.

PMID- 23161586
TI  - Exploring the utility of institutional theory in analysing international health
      agency stasis and change.
AB  - Of recent interest is the capacity of international health agencies to adapt to
      changes in the global health environment and country needs. Yet, little is known
      about the potential benefits of using social science institutional theory, such
      as path dependency and institutional change theory, to explain why some
      international agencies, such as the WHO and the Global Fund to Fight AIDS,
      Tuberculosis and Malaria, fail to adapt, whereas others, such as the World Bank
      and UNAIDS, have. This article suggests that these institutional theories can
      help to better understand these differences in international agency adaptive
      capacity, while highlighting new areas of policy research and analysis. 

PMID- 23161587
TI  - Willingness to pay for private primary care services in Hong Kong: are elderly
      ready to move from the public sector?
AB  - How to provide better primary care and achieve the right level of public-private
      balance in doing so is at the centre of many healthcare reforms around the world.
      In a healthcare system like Hong Kong, where inpatient services are largely
      funded through general taxation and ambulatory services out of pocket, the family
      doctor model of primary care is underdeveloped. Since 2008, the Government has
      taken forward various initiatives to promote primary care and encourage more use
      of private services. However, little is known in Hong Kong or elsewhere about
      consumers' willingness to pay (WTP) for private services when care is available
      in the public sector. This study assessed willingness of the Hong Kong elderly to
      pay for specific primary care and preventive services in the private sector,
      through a cross-sectional in-person questionnaire survey and focus group
      discussions among respondents. The survey revealed that the WTP for private
      services in general was low among the elderly; particularly, reported WTP for
      chronic conditions and preventive care both fell below the current market prices.
      Sub-group analysis showed higher WTP among healthier and more affluent elderly.
      Among other things, concerns over affordability and uncertainty (of price and
      quality) in the private sector were associated with this low level of WTP. These
      results suggest that most elderly, who are heavy users of public health services
      but with limited income, may not use more private services without seeing
      significant reduction in price. Financial incentives for consumers alone may not
      be enough to promote primary care or public-private partnership. Public education
      on the value of prevention and primary care, as well as supply-side interventions
      should both be considered. Hong Kong's policy-making process of the initiative
      studied here may also provide lessons for other countries with ongoing healthcare
      reforms. 

PMID- 23161588
TI  - Brokering the boundary between science and advocacy: the case of intermittent
      preventive treatment among infants.
AB  - The process of translating research into policy has gained considerable attention
      in recent years and a number of studies have investigated the nexus between the
      two 'worlds' of research and policy. One issue that has been little addressed is
      about the boundaries between research and advocacy: how far scientists do, or
      should, promote particular findings to policy makers and others. This article
      analyses a particular intervention in malaria control and the Consortium set up
      to accelerate its potential implementation. Using a framework that emphasizes the
      interplay of interests, institutions and ideas, it provides an example of how a
      network of committed researchers and funders attempted to follow a rational
      policy process, but faced conflicts and fundamental questions about their roles
      in generating scientific evidence and influencing global health policy. In an era
      of ever more and larger researcher groups and consortia, the findings offer
      insights and lessons to those engaged in the process of knowledge translation. 

PMID- 23161590
TI  - A nascent proteome study combining click chemistry with 2DE.
AB  - To investigate the dynamic cellular response to a condition change, selective
      labeling of the nascent proteome is necessary. Here, we report a method combining
      click chemistry protein labeling with 2D DIGE. To test the relevance of the
      method, we compared nascent proteomes of actively growing bacterial cells with
      that of cells exposed to protein synthesis inhibitor, erythromycin. Cells were
      incubated with methionine analog, homopropargyl glycin, and their nascent
      proteome was selectively labeled with monosulfonated neutral Cy3 and Cy5 azides
      specially synthesized for this purpose. Following fluorescent labeling, the
      protein samples were mixed and subjected to standard 2D DIGE separation. The
      method allowed us to reveal a dramatic reduction of newly synthesized proteins
      upon erythromycin treatment, while the total proteome was not significantly
      affected. Additionally, several proteins, whose synthesis was resistant to
      erythromycin, were identified.

PMID- 23161592
TI  - The 27th International Symposium on MicroScale Bioseparations (formerly the HPCE
      Series) took place February 12-15, 2012. Introduction.

PMID- 23161591
TI  - Clinical ethics consultation in patients with head and neck cancer.
AB  - BACKGROUND: The purpose of this study was to describe the impact of clinical
      ethics consultations among patients with head and neck cancer in order to better
      anticipate and manage clinical challenges. METHODS: A database was queried to
      identify patients with head and neck cancer for whom ethics consultation was
      performed at a comprehensive cancer center (n = 14). Information from the
      database was verified via data abstraction and analyzed qualitatively and
      quantitatively. RESULTS: Common requests for ethics consultation involved code
      status (6 of 14) and withdrawal/withholding life-sustaining treatments (6 of 14).
      Common contextual features were interpersonal conflicts (6 of 14) and
      communication barriers (5 of 14). Airway management concerns were frequent (5 of
      14). Whereas 21% of patients had do not resuscitate (DNR) orders before ethics
      consultation, 79% were DNR subsequently. CONCLUSION: Ethics consultations among
      patients with head and neck cancer reflect distinctive complexities inherent to
      their disease, but are entirely consistent with global clinical ethical themes.
      Consideration of communication barriers, social isolation/stigma, symptom
      control, and airway management are critical.

PMID- 23161593
TI  - Pier-Giorgio Righetti wins the inaugural Beckman Award.

PMID- 23161598
TI  - Quantitative microfluidic analysis of S- and R-type endotoxin components with
      chip capillary electrophoresis.
AB  - A novel, fast, and sensitive ME method was developed to analyze and differentiate
      the smooth (S) and rough (R) type bacterial endotoxin components labeled
      covalently with a fluorescent dye. The quantitative analysis of purified
      lipopolysaccharides, or partially purified samples from whole-cell lysates
      becomes possible with this method. Two groups with three sub-groups in the first
      group of S-type lipopolysaccharides can be classified based on the
      electrophoretic profiles. The LOD of the endotoxins from S- and R-type Gram
      negative bacteria was found to be 2.6 ng and 6.9 ng, respectively. This method is
      capable to replace the commonly used SDS-PAGE combined with silver staining.

PMID- 23161599
TI  - Lessons learned from a comparison of evidence-based research in pregnant opioid
      dependent women.
AB  - OBJECTIVES: Lessons learned in research and treatment of opioid dependence
      demonstrate the need to include pregnant women in clinical trials. METHODS: Two
      double-blind, double-dummy, randomized controlled trials (Pilot study, European
      sample(?) of MOTHER-trial) comparing buprenorphine and methadone in opioid
      dependent pregnant women were conducted. In both studies, participants received
      voucher-based incentives for attendance and completion of study assessments. In
      the MOTHER trial, participants additionally received escalating voucher
      incentives for drug-free urine samples. Neonatal abstinence syndrome was treated
      with oral morphine solution based on standardized modified Finnegan scores.
      RESULTS: After a mean treatment period of 13.79 weeks in the Pilot study (PS, n =
      18) and 20.78 weeks in the MOTHER-trial (MT, n = 41), respectively (p < 0.001),
      PS patients delivered at mean doses of 14.00 mg buprenorphine/52.50 mg methadone
      and MT participants at 13.44 mg buprenorphine/63.68 mg methadone. Nonsignificant
      differences regarding dropout rates were found (22% in PS versus 10% in MT), but
      dropout was significantly earlier in the MT (p = 0.013). Significantly higher
      rates of concomitant consumption of opioids and benzodiazepines occurred in the
      PS compared with the MT (p < 0.001), however, with no significant differences in
      neonatal data between both settings. CONCLUSIONS: Early treatment enrolment
      combined with contingency management contributes to reduced illicit drug use
      throughout pregnancy, surprisingly without influencing neonatal outcome
      parameters.

PMID- 23161600
TI  - Universal fluorescent labeling of amplification products using locked nucleic
      acids.
AB  - Amplification/hybridization-based genetic analyses using primers containing
      locked nucleic acids (LNAs) present many benefits. Here, we developed a novel
      design for universal fluorescent PCR using LNAs. Universal fluorescent PCR
      generates intermediate nonlabeled fragments and final fluorescent fragments in a
      two-step amplification process that uses locus-specific primers with universal
      tails and universal fluorescent primers. In this study, a few standard
      nucleotides were replaced with LNAs only in the fluorescent universal primers.
      The sequence of the fluorescent universal primer significantly affected the
      amplification efficiency. For primers with three LNAs, the fluorescent primers
      with stable M13(-47) sequences provided the most efficient signal (approximately
      tenfold higher than the primers with M13(-21) sequences at lower Tm values).
      Moreover, AT-rich LNA substitutions in the fluorescent primers produced much
      lower amplification efficiencies than GC-rich substitutions. GC-rich LNAs
      produced greater differences in Tm values among primers, and resulted in the
      preferential production of fluorescently labeled amplicons. The specificity and
      sensitivity of LNA-containing fluorescent primers were assessed by genotyping
      eight STRs in Japanese individuals, and full STR profiles could be generated
      using as little as 0.25 ng of genomic DNA. The method permitted clear
      discrimination of alleles and represents sensitive STR genotyping at a reduced
      cost.

PMID- 23161601
TI  - Analysis of thiols by microchip capillary electrophoresis for in situ planetary
      investigations.
AB  - The detection of thiols on extraterrestrial bodies could provide evidence for
      life, as well as a host of potential prebiological or abiological processes.
      Here, we report a novel protocol to analyze organic thiols by microchip CE with
      LIF detection. Thiols were labeled with Pacific Blue C5 maleimide and analyzed by
      MEKC. The separation buffer consisted of 15 mM tetraborate pH 9.2 and 25 mM SDS.
      The optimized method provided LODs ranging from 1.4 to 15 nM. The method was
      validated using samples collected from geothermal pools at Hot Creek Gorge,
      California, which were found to contain 2-propanethiol and 1-butanethiol in the
      nanomolar concentration range. These samples serve as chemical analogues to
      material potentially present in the reducing environment of primitive Earth and
      also at sulfurous regions of Mars. Hence, the protocol developed here enables
      highly sensitive thiol analysis in samples with complexity comparable to that
      expected in astrobiologically relevant extraterrestrial settings. This new
      protocol could be readily added to the existing suite of microfluidic chemical
      analyses developed for in situ planetary exploration; all that is required is the
      incorporation of two new reagents to the payload of an existing instrument
      concept.

PMID- 23161602
TI  - Gold for the generation and control of fluxional barbaralyl cations.
AB  - The frog prince with his two identities pales in comparison with the shape
      shifting barbaralyl cation, which exists as a mixture of 181,400 degenerate
      forms. Gold-catalyzed cycloisomerizations of 7-alkynyl cyclohepta-1,3,5-trienes
      were found to proceed via fluxional barbaralyl intermediates. The evolution of
      the intermediates into 1- or 2-substituted indenes could be controlled by the
      choice of gold complex.

PMID- 23161603
TI  - Protein and peptide profiling as a tool for biomarker discovery in depression.
AB  - This study sought to determine whether protein and/or peptide profiles from serum
      were able to distinguish patients suffering from depression from healthy control
      subjects and thereby act as biomarker candidates with potential diagnostic value.
      Serum samples were collected from patients (n = 39) and controls (n = 30). A C8
      magnetic bead protocol was used to prepare serum proteins, while a
      microextraction C18 packed tip was used to isolate serum peptides. Both protein
      and peptide profiles were recorded by MALDI-MS and the data were exported for
      further analysis. No protein signals differentiated patients from controls and
      principle component analysis of the entire peptide profile did not allow for
      distinct clustering of the two groups. Further analysis of individual peptides
      however identified three peptide signals whose intensities were significantly
      different between patients and control subjects. The efficacy of these potential
      biomarker candidates to identify the patients was therefore studied using a
      receiver operating characteristic (ROC) curve and the combined use of all three
      candidates together offered the most specific and sensitive identification of
      true positive cases of depression.

PMID- 23161604
TI  - Reduction of borazines mediated by low-valent chromium species.
AB  - Recharging spent BN fuel: {Cr(CO)(3)} mediates the reduction of borazines by
      hydride and methyl nucleophiles to generate anionic complexes of dearomatized
      hexamethylborazine. Subsequent quenching leads to the release of a substituted
      cyclotriborazane, successfully demonstrating the stepwise reduction of a B=N
      bond.

PMID- 23161605
TI  - Quantitative mass spectrometry-based proteomics in angiogenesis.
AB  - The process of new blood vessel formation from pre-existing ones is called
      angiogenesis. Beyond playing a critical role in the physiological development of
      the vascular system, angiogenesis is a well-recognised hallmark of cancer.
      Unbiased system-wide approaches are required to complement the current knowledge,
      and intimately understand the molecular mechanisms regulating this process in
      physiological and pathological conditions. In this review we describe the
      cellular and molecular dynamics regulating the physiological growth of vessels
      and their deregulation in cancer, survey in vitro and in vivo models currently
      exploited to investigate various aspects of angiogenesis and describe state-of
      the-art and most widespread methods and technologies in MS shotgun proteomics.
      Finally, we focus on current applications of MS to better understand endothelial
      cell behaviour and propose how modern proteomics can impact on angiogenesis
      research. 

PMID- 23161606
TI  - Impressive activity of lenalidomide monotherapy in refractory angioimmunoblastic
      T-cell lymphoma: report of a case with long-term follow-up.
AB  - Angioimmunoblastic T-cell lymphoma (AITL) is characterized by an aggressive
      clinical course and unfavourable prognosis. Refractory AITL patients have very
      few treatment options. Lenalidomide has previously been reported to have clinical
      efficacy in this setting; however, long-term reports are limited. A 59-year-old
      man was referred to the hospital with fatigue, skin rash, weight loss and
      generalized lymphadenopathy and was diagnosed with AITL; clinical stage was IV B
      with bone marrow involvement. The patient had an unsatisfactory response despite
      three lines of conventional chemotherapy and radiotherapy. The patient received
      lenalidomide monotherapy (25 mg once daily) on days 1 to 21 of every 28-day cycle
      for six cycles, followed by maintenance therapy with six cycles of lenalidomide
      15 mg once daily on days 1 to 21 of every 28-day cycle. A computed tomography
      scan was assessed before lenalidomide treatment, after the third cycle, at
      disease restaging 2 months after completion of the induction phase, every 3
      months during the maintenance phase and every 6 months during the follow-up
      period. At the last evaluation, after a follow-up of 30 months, the patient
      maintained a clinical and radiological complete response. The treatment was well
      tolerated with manageable toxicity. Lenalidomide treatment demonstrated for the
      first time in the literature impressive and long-term clinical efficacy in a
      heavily pretreated chemorefractory AITL patient.

PMID- 23161607
TI  - Serial anthropometry predicts peripheral nerve dysfunction in a community cohort.
AB  - BACKGROUND: Obesity is a risk factor for glucose intolerance, but the independent
      role of obesity in the development of peripheral neuropathy is unclear. This
      study assessed the impact of body size trajectories on prevalent nerve
      dysfunction in community-dwelling women with and without glucose intolerance.
      METHODS: Annual (1996-2008) anthropometric measures of weight, height, waist
      circumference and body mass index [BMI, weight (kg)/height (m(2) )] were assessed
      in the Study of Women's Health Across the Nation - Michigan site. Glucose
      intolerance was defined annually on the basis of current use of diabetes
      medications, self-reported diabetes diagnosis and, when available, fasting
      glucose. Peripheral nerve dysfunction in 2008 was defined as abnormal
      monofilament testing or >=4 symptoms or signs. Linear mixed models were used to
      determine trajectories of anthropometry by subsequently identified nerve
      dysfunction status. RESULTS: Mean BMI was 32.4 kg/m(2) at baseline, and 27.8% of
      the women had nerve dysfunction in 2008. BMI, weight and waist circumference
      increased over time. Women who would have nerve dysfunction were significantly
      larger than women without dysfunction, independent of glucose intolerance. At
      mean baseline age of 46, BMI, weight and waist circumference differed
      significantly (p-value < 0.01) by subsequent nerve dysfunction status,
      independent of glucose intolerance and hypertension. These body size differences
      were maintained but not exacerbated over time. CONCLUSIONS: Peripheral nerve
      dysfunction is prevalent among community-dwelling women. Twelve years before the
      nerve assessment, anthropometry differed between women who would and would not
      have nerve dysfunction, differences that were maintained over time. Obesity
      deserves attention as an important and potentially modifiable risk factor for
      peripheral nerve dysfunction.

PMID- 23161609
TI  - Women who drink heavily during pregnancy have increased stillbirth risk.

PMID- 23161608
TI  - Transcription factors link mouse WAP-T mammary tumors with human breast cancer.
AB  - Mouse models are important tools to decipher the molecular mechanisms of mammary
      carcinogenesis and to mimic the respective human disease. Despite sharing common
      phenotypic and genetic features, the proper translation of murine models to human
      breast cancer remains a challenging task. In a previous study we showed that in
      the SV40 transgenic WAP-T mice an active Met-pathway and epithelial-mesenchymal
      characteristics distinguish low- and high-grade mammary carcinoma. To assign
      these murine tumors to corresponding human tumors we here incorporated the
      analysis of expression of transcription factor (TF) coding genes and show that
      thereby a more accurate interspecies translation can be achieved. We describe a
      novel cross-species translation procedure and demonstrate that expression of
      unsupervised selected TFs, such as ELF5, HOXA5 and TFCP2L1, can clearly
      distinguish between the human molecular breast cancer subtypes--or as, for
      example, expression of TFAP2B between yet unclassified subgroups. By integrating
      different levels of information like histology, gene set enrichment, expression
      of differentiation markers and TFs we conclude that tumors in WAP-T mice exhibit
      similarities to both, human basal-like and non-basal-like subtypes. We
      furthermore suggest that the low- and high-grade WAP-T tumor phenotypes might
      arise from distinct cells of tumor origin. Our results underscore the importance
      of TFs as common cross-species denominators in the regulatory networks underlying
      mammary carcinogenesis.

PMID- 23161610
TI  - Src kinase is a direct target of apigenin against UVB-induced skin inflammation.
AB  - Apigenin, a flavonoid abundant in various vegetables and fruits, including
      parsley and onions, has been reported to possess anticarcinogenic effects.
      However, the direct molecular target of apigenin and its chemopreventive effect
      on ultraviolet (UV)-induced skin inflammation are not understood fully. Herein,
      we examined the anti-inflammatory effect of apigenin and its associated
      mechanisms in JB6 P+ cell line and SKH-1 hairless mouse model. Apigenin inhibited
      UVB-induced cyclooxygenase-2 (COX-2) expression, which is a well-known key
      mediator of inflammation and cancer, and restored the upstream stimulatory factor
      level in JB6 P+ cells. Immunoblot and kinase assay data demonstrate that Src
      activity was attenuated by apigenin, and this led to subsequent inhibition of UVB
      induced phosphorylation of epidermal growth factor receptor, mitogen-activated
      protein kinases and Akt signaling. Inhibitory effects of apigenin on UVB-induced
      signaling were also confirmed in HaCaT human keratinocytes. In addition, in vitro
      pull-down assays revealed that apigenin binds Src in an adenosine triphosphate
      competitive manner. Results using in vivo skin model indicate apigenin
      significantly inhibits UVB-induced ear edema development, COX-2 expression and
      Src kinase activity in SKH-1 hairless mice. Collectively, these findings suggest
      that apigenin exerts potent chemopreventive activity against UVB-induced skin
      inflammation primarily by targeting Src.

PMID- 23161611
TI  - Time-dependent species sensitivity distributions.
AB  - Time is a central component of toxicity assessments. However, current
      ecotoxicological practice marginalizes time in concentration-response (C-R)
      modeling and species sensitivity distribution (SSD) analyses. For C-R models,
      time is invariably fixed, and toxicity measures are estimated from a function
      fitted to the data at that time. The estimated toxicity measures are used as
      inputs to the SSD modeling phase, which similarly avoids explicit recognition of
      the temporal component. The present study extends some commonly employed
      probability models for SSDs to derive theoretical results that characterize the
      time-dependent nature of hazardous concentration (HCx) values. The authors'
      results show that even from very simple assumptions, more complex patterns in the
      SSD time dependency can be revealed.

PMID- 23161612
TI  - Development and preliminary validation of the Patient Perceptions of Integrated
      Care survey.
AB  - Valid measures of the integration of patient care could provide rapid and
      accurate feedback on the successfulness of current efforts to improve health care
      delivery systems. This article describes the development and pilot testing of a
      new survey, based on a novel conceptual model, which measures the integration of
      patient care as experienced by patients. We administered the survey to 1,289
      patients with multiple chronic conditions from one health system and received
      responses from 527 patients (43%). Psychometric analysis of responses supported a
      six-dimension model of integration with satisfactory internal consistency,
      discriminant validity, and goodness of fit. The Patient Perceptions of Integrated
      Care survey can be used to measure the integration of care received by
      chronically ill patients for two main purposes: as a research tool to compare
      interventions intended to improve the integration of care and as a quality
      improvement tool intended to guide the refinement of delivery system innovations.

PMID- 23161613
TI  - Learning the law: practical proposals for UK medical education.
AB  - Ongoing serious breaches in medical professionalism might be avoided if UK
      doctors rethink their approach to law. UK medical education has a role in
      creating a climate of change by re-examining how law is taught to medical
      students. Adopting a more insightful approach in the UK to the impact of The
      Human Rights Act and learning to manipulate legal concepts, such as conflict of
      interest, need to be taught to medical students now if UK doctors are to manage
      complex decision-making in the NHS of the future. The literature is reviewed from
      a unique personal perspective of a doctor and lawyer, and practical proposals for
      developing medical education in law in the UK are suggested. 

PMID- 23161614
TI  - Recruiting medics from the poorest nations? It could be worse....

PMID- 23161615
TI  - Still afraid of needy post-persons.

PMID- 23161616
TI  - Killing versus totally disabling: a reply to critics.

PMID- 23161617
TI  - Phase 1 oncology trials and informed consent.
AB  - Ethical concerns have been raised about the quality of informed consent by
      participants in phase 1 oncology trials. Interview surveys indicate that
      substantial proportions of trial participants do not understand the purpose of
      these trials-evaluating toxicity and dosing for subsequent efficacy studies-and
      overestimate the prospect of therapeutic benefit that they offer. In this article
      we argue that although these data suggest the desirability of enhancing the
      process of information disclosure and assessment of comprehension of the
      implications of study participation, they do not necessarily invalidate consent
      by phase 1 trial participants. 

PMID- 23161618
TI  - Triglycerides and cardiovascular risk.

PMID- 23161619
TI  - Protein chimerism: novel source of protein diversity in humans adds complexity to
      bottom-up proteomics.
AB  - Three main molecular mechanisms are considered to contribute expanding the
      repertoire and diversity of proteins present in living organisms: first, at DNA
      level (gene polymorphisms and single nucleotide polymorphisms); second, at
      messenger RNA (pre-mRNA and mRNA) level including alternative splicing (also
      termed differential splicing or cis-splicing); finally, at the protein level
      mainly driven through PTM and specific proteolytic cleavages. Chimeric mRNAs
      constitute an alternative source of protein diversity, which can be generated
      either by chromosomal translocations or by trans-splicing events. The occurrence
      of chimeric mRNAs and proteins is a frequent event in cells from the immune
      system and cancer cells, mainly as a consequence of gene rearrangements. Recent
      reports support that chimeric proteins may also be expressed at low levels under
      normal physiological circumstances, thus, representing a novel source of protein
      diversity. Notably, recent publications demonstrate that chimeric protein
      products can be successfully identified through bottom-up proteomic analyses.
      Several questions remain unsolved, such as the physiological role and impact of
      such chimeric proteins or the potential occurrence of chimeric proteins in higher
      eukaryotic organisms different from humans. The occurrence of chimeric proteins
      certainly seems to be another unforeseen source of complexity for the proteome.
      It may be a process to take in mind not only when performing bottom-up proteomic
      analyses in cancer studies but also in general bottom-up proteomics experiments.

PMID- 23161620
TI  - Biomarkers of inflammation are associated with colorectal cancer risk in women
      but are not suitable as early detection markers.
AB  - Initial studies have investigated the association between inflammation and
      colorectal cancer (CRC) using C-reactive protein (CRP) as a proinflammatory
      biomarker and have noted inconsistent results among women. We here report the
      findings from a large prospective study with repeat measurements of CRP, as well
      as serum amyloid A (SAA), an additional biomarker of inflammation, and risk of
      CRC. In the Women's Health Initiative Observational Study, we examined
      associations of CRP and SAA with CRC using repeat assessments (baseline and 3
      year follow-up) among 953 matched case-control pairs for CRP and 966 pairs for
      SAA. Multivariate-adjusted conditional-logistic regression models were used with
      two-sided tests of significance. Receiver operating characteristic (ROC) curve
      analysis assessed their utility as early detection markers. Colon cancer risk
      (odds ratio [OR] and 95% confidence intervals) among women in the highest
      quintiles of CRP or SAA compared to those in the lowest quintiles was ORcolon/CRP
      = 1.37 (0.95-1.97, p-trend = 0.04) and ORcolon/SAA = 1.26 (0.88-1.80, p-trend =
      0.10), respectively. Women with elevated concentrations of both CRP and SAA had
      an increased risk of ORcolon = 1.50 (1.12-2.00, p-value = 0.006) compared to
      those with low concentrations. No positive associations were observed with rectal
      cancer and weaker associations for CRC overall. Temporal changes in biomarkers
      more than 3 years did not predict risk. The area under the 6-month ROC curve for
      CRP+SAA was 0.62 (95% confidence interval = 0.55-0.68). Elevated inflammatory
      biomarkers are associated with an increased risk of CRC, mainly colon cancer.
      Nevertheless, changes in the biomarkers over time do not suggest that they merit
      consideration as early detection markers for CRC.

PMID- 23161621
TI  - Changes in QT interval after switching to quetiapine in Japanese patients with
      schizophrenia.
AB  - OBJECTIVES: There are few reports regarding quetiapine (QTP)-related QT
      prolongation. We examined the change in QT interval after switching from
      aripiprazole (ARP), olanzapine (OLZ), or risperidone (RIS) to QTP. METHODS:
      Twenty subjects treated with ARP, OLZ, or RIS were enrolled in the study.
      Following baseline assessments, which included QT interval and electrolytes,
      these three drugs were switched to QTP for each subject. The same parameters were
      evaluated following a switch to QTP. RESULTS: All 20 patients who had been
      treated with ARP, OLZ, or RIS were successfully switched to QTP. Significant
      increases were observed in the total mean corrected QT (QTc) interval after
      switching (p = 0.014). The coefficient of variation for the extent of change in
      QTc interval was 1.66. The mean QTc with ARP treatment was significantly
      increased after QTP treatment (p = 0.004). CONCLUSIONS: Quetiapine might have a
      greater effect on QTc interval than other second-generation antipsychotics.
      However, because there was a considerable variability in the extent of QTc
      prolongation after switch to QTP, further studies are required to clarify the
      effect of QTP on QTc interval.

PMID- 23161623
TI  - Physiological importance of poly-(R)-3-hydroxybutyrates.
AB  - Poly-(R)-3-hydroxybutyrates (PHB), linear polymers of (R)-3-hydroxybutyrate, are
      components of all biological cells in which short polymers (<200 monomer
      residues) are covalently attached to certain proteins and/or noncovalently
      associated with polyphosphates - inorganic polyphosphate (polyP), RNA, and DNA.
      The low concentrations, lack of unusual atoms or functional groups, and flexible
      backbones of this complexed PHB, referred to as cPHB, make them invisible to many
      analytical procedures; whereas other physical properties - water-insolubility,
      high intrinsic viscosity, temperature sensitivity, multiple bonding interactions
      with other molecules - make them requisite participants in vital physiological
      processes as well as contributors to the development of certain diseases.

PMID- 23161622
TI  - An accurate multiplex antibiotic susceptibility test using a high-resolution CE
      SSCP-based stuffer-free multiplex ligation-dependent probe amplification system.
AB  - The success of antimicrobial therapy depends on effective prescription of
      antibiotics. Assessment of clinical isolates using rapid antimicrobial
      susceptibility tests allows effective microbiological therapy to be commenced in
      a timely manner. However, conventional antimicrobial susceptibility testing is
      time-consuming and laborious. In the present study, we employed stuffer-free
      multiplex ligation-dependent probe amplification (MLPA) coupled with analysis of
      single-strand conformation polymorphisms, via high-resolution CE, to develop a
      multiplex antibiotic susceptibility test. Using this method, parallel analysis of
      specific genetic markers was employed to determine minimal inhibitory
      concentration values. The values derived using the stuffer-free MLPA method
      agreed with those estimated using a conventional broth dilution method. These
      findings indicate that the stuffer-free MLPA-based approach is a viable
      alternative to the conventional method.

PMID- 23161624
TI  - Neuropeptides and neuropeptide receptors: drug targets, and peptide and non
      peptide ligands: a tribute to Prof. Dieter Seebach.
AB  - The number of neuropeptides and their corresponding receptors has increased
      steadily over the last fourty years: initially, peptides were isolated from gut
      or brain (e.g., Substance P, somatostatin), then by targeted mining in specific
      regions (e.g., cortistatin, orexin in the brain), or by deorphanization of G
      protein-coupled receptors (GPCRs; orexin, ghrelin receptors) and through the
      completion the Human Genome Project. Neuropeptides (and their receptors) have
      regionally restricted distributions in the central and peripheral nervous system.
      The neuropeptide signaling is somewhat more distinct spatially than signaling
      with classical, low-molecular-weight neurotransmitters that are more widely
      expressed, and, therefore, one assumes that drugs acting at neuropeptide
      receptors may have more selective pharmacological actions with possibly fewer
      side effects than drugs acting on glutamatergic, GABAergic, monoaminergic, or
      cholinergic systems. Neuropeptide receptors, which may have a few or multiple
      subtypes and splice variants, belong almost exclusively to the GPCR family also
      known as seven-transmembrane receptors (7TM), a favorite class of drug targets in
      the pharmaceutical industry. Most neuropeptides are co-stored and co-released
      with classic neurotransmitters, albeit often only at higher frequencies of
      stimulation or at bursting activity, thus restricting the neuropeptide signaling
      to specific circumstances, another reason to assume that neuropeptide drug mimics
      may have less side effects. Neuropeptides possess a wide spectrum of functions
      from neurohormone, neurotransmitter to growth factor, but also as key
      inflammatory mediators. Neuropeptides become 'active' when the nervous system is
      challenged, e.g., by stress, injury, drug abuse, or neuropsychiatric disorders
      with genetic, epigenetic, and/or environmental components. The unsuspected number
      of true neuropeptides and their cognate receptors provides opportunities to
      identify novel targets for the treatment of both central and peripheral nervous
      system disorders. Both, receptor subtype-selective antagonists and agonists are
      being developed, as illustrated by the success of somatostatin agonists,
      angiotensin, and endothelin antagonists, and the expected clinical applications
      of NK-1/2/3 (substance P) receptor antagonists, CRF, vasopressin, NPY,
      neurotensin, orexin antagonists, or neuropeptide receptor modulators; such
      ligands have efficacy in preclinical or clinical models of pain and
      neuropsychiatric diseases, such as migraine, chronic/neuropathic pain, anxiety,
      sleep disorders, depression, and schizophrenia. In addition, both positive and
      negative allosteric modulators have been described with interesting in vivo
      activities (e.g., at galanin receptors). The field has become more complex now
      that an increasing number of heteromeric neuropeptide receptors are described,
      e.g., ghrelin receptors with 5-HT(2C) or dopamine D(1), D(2) receptors. At long
      last, structure-based drug discovery can now be envisaged with confidence, since
      crystal or solution structure of GPCRs and GPCR-ligand complexes, including
      peptide receptors, are published almost on a monthly basis. Finally, although
      most compounds acting at peptide receptors are still peptidomimetics, the last
      decade has seen the emergence of low-molecular-weight nonpeptide ligands (e.g.,
      for orexin, ghrelin, or neurokinin receptors), and surprising progress has been
      made with beta- and gamma-peptides as very stable and potent mimetics of, e.g.,
      somatostatin (SRIF), where the native SRIF has a half-life limited to 2-3 min.
      This last point will be illustrated more specifically, as we have had a long
      standing collaboration with Prof. D. Seebach to whom this review is dedicated at
      the occasion of his 75th birthday.

PMID- 23161625
TI  - Bacterial beta-aminopeptidases: structural insights and applications for
      biocatalysis.
AB  - beta-Aminopeptidases comprise a class of enzymes with functional and structural
      similarities. All members of the beta-aminopeptidases described to date were
      isolated from bacterial sources. Uniquely, they catalyze the hydrolysis of
      beta(3) - and/or beta(2) -amino acid residues from amides and peptides that are
      otherwise considered proteolytically stable. Due to this unusual reactivity with
      beta-peptide substrates, beta-aminopeptidases have potential to be used as
      biocatalysts for beta-peptide synthesis and for the resolution of
      enantiomerically pure beta-amino acids from racemic substrate mixtures. beta
      Aminopeptidases are formed from an inactive precursor by posttranslational
      autoproteolytic cleavage, exposing the catalytic nucleophile at the N-terminus of
      the newly formed beta-polypeptide chain. Such an activation step is a
      characteristic trait of enzymes of the N-terminal nucleophile (Ntn) hydrolase
      superfamily. However, classical Ntn hydrolases and beta-aminopeptidases differ by
      the fold of their catalytic cores and are hence likely to originate from distinct
      evolutionary ancestors. In this contribution, we review the existing literature
      on beta-aminopeptidases, including biochemical and functional studies, as well as
      structural investigations that recently allowed insights into the catalytic
      mechanisms of precursor processing and beta-peptide conversion.

PMID- 23161626
TI  - Synthesis, structure, and biological applications of alpha-fluorinated beta-amino
      acids and derivatives.
AB  - This review gives a broad overview of the state of play with respect to the
      synthesis, conformational properties, and biological activity of alpha
      fluorinated beta-amino acids and derivatives. General methods are described for
      the preparation of monosubstituted alpha-fluoro-beta-amino acids (Scheme 1).
      Nucleophilic methods for the introduction of fluorine predominantly involve the
      reaction of DAST with alcohols derived from alpha-amino acids, whereas
      electrophilic sources of fluorine such as NFSI have been used in conjunction with
      Arndt-Eistert homologation, conjugate addition or organocatalyzed Mannich
      reactions. alpha,alpha-Difluoro-beta-amino acids have also been prepared using
      DAST; however, this area of synthesis is largely dominated by the use of
      difluorinated Reformatsky reagents to introduce the difluoro ester functionality
      (Scheme 9). alpha-Fluoro-beta-amino acids and derivatives analyzed by X-ray
      crystal and NMR solution techniques are found to adopt preferred conformations
      which are thought to result from stereoelectronic effects associated with F
      located close to amines, amides, and esters (Figs. 2-6). alpha-Fluoro amide and
      beta-fluoro ethylamide/amine effects can influence the secondary structure of
      alpha-fluoro-beta-amino acid-containing derivatives including peptides and
      peptidomimetics (Figs. 7-9). alpha-Fluoro-beta-amino acids are also components of
      a diverse range of bioactive anticancer (e.g., 5-fluorouracil), antifungal, and
      antiinsomnia agents as well as protease inhibitors where such fluorinated analogs
      have shown increased potency and spectrum of activity.

PMID- 23161627
TI  - Imidazopyridine-based inhibitors of glycogen synthase kinase 3: synthesis and
      evaluation of amide isostere replacements of the carboxamide scaffold.
AB  - In this study, we explored the effect of bioisostere replacement in a series of
      glycogen synthase kinase 3 (GSK3) inhibitors based on the imidazopyridine core.
      The synthesis and biological evaluation of a number of novel sulfonamide, 1,2,4
      oxadiazole, and thiazole derivates as amide bioisosteres, as well as a
      computational rationalization of the obtained results are reported.

PMID- 23161629
TI  - New tripeptide-based macrocyclic calpain inhibitors formed by N-alkylation of
      histidine.
AB  - Two new series of 15-membered macrocyclic peptidomimetics, in which the P1 and P3
      residues of the peptide backbone are linked by a bridge containing a 1,4
      disubstituted 1H-imidazole, are reported. The structure with an aldehyde at the C
      terminus and the imidazole at P3, i.e., 4c, shows significant inhibitory activity
      against calpain 2, with an IC(50) value of 238 nM. The macrocyclic aldehyde with
      the imidazole at the alternative P1 position, i.e., 5c, is significantly less
      active. The relative activities are linked to the ability of the component
      macrocycles to mimic a beta-strand geometry that is known to favor active-site
      binding. This ability is defined by conformational searches and docking studies
      with calpain.

PMID- 23161628
TI  - Efficient preparation of giant vesicles as biomimetic compartment systems with
      high entrapment yields for biomacromolecules.
AB  - The 'lipid-coated ice-droplet hydration method' was applied for the preparation
      of milliliter volumes of a suspension of giant phospholipid vesicles containing
      in the inner aqueous vesicle pool in high yield either calcein, alpha
      chymotrypsin, fluorescently labeled bovine serum albumin or dextran (FITC-BSA and
      FITC-dextran; FITC=fluorescein isothiocyanate). The vesicles had an average
      diameter of ca. 7-11 MUm and contained 20-50% of the desired molecules to be
      entrapped, the entrapment yield being dependent on the chemical structure of the
      entrapped molecules and on the details of the vesicle-formation procedure. The
      'lipid-coated ice droplet hydration method' is a multistep process, based on i)
      the initial formation of a monodisperse water-in-oil emulsion by microchannel
      emulsification, followed by ii) emulsion droplet freezing, and iii) surfactant
      and oil removal, and replacement with bilayer-forming lipids and an aqueous
      solution. If one aims at applying the method for the entrapment of enzymes,
      retention of catalytic activity is important to consider. With alpha-chymotrypsin
      as first model enzyme to be used with the method, it was shown that high
      retention of enzymatic activity is possible, and that the entrapped enzyme
      molecules were able to catalyze the hydrolysis of a membrane-permeable substrate
      which was added to the vesicles after their formation. Furthermore, one of the
      critical steps of the method that leads to significant release of the molecules
      from the water droplets was investigated and optimized by using calcein as
      fluorescent probe.

PMID- 23161630
TI  - DNA triplex-mediated assembly of polyaromatic chromophores.
AB  - The synthesis and characterization of intramolecular triple-helical DNA
      structures containing polyaromatic pyrene and perylene (perylenetetracarboxylic
      acid diimide, PDI) building blocks are presented. Two 1,8-dialkynylpyrene units
      are located in the Watson-Crick stem of the construct, while a PDI or a natural
      thymidine is present in the Hoogsteen strand. The triple helical structures were
      investigated by UV/VIS absorbance, fluorescence spectroscopy, and circular
      dichroism (CD) measurements. The folding of the intramolecular triple helix can
      be monitored by changes in the vibronic transition ratios, as well as by a change
      in the alkynylpyrene fluorescence (monomer vs. excimer). It is shown that thymine
      in the third strand has a pronounced influence on the interaction and, thus, on
      the fluorescence properties of two pyrene building blocks.

PMID- 23161631
TI  - Synthesis and biological evaluation of gramicidin S-inspired cyclic mixed
      alpha/beta-peptides.
AB  - Via a Mannich reaction involving a dibenzyliminium species and the titanium
      enolates of Evans' chiral acylated oxazolidinones the beta(2)-amino acids (R)-
      and (S)-Fmoc-beta(2)homovaline and (R)-Fmoc-beta(2)homoleucine are synthesized.
      These building blocks were used, in combination with commercially available alpha
      and beta(3)-amino acids, for the synthesis of the cyclo
      (alphabeta(3)alphabeta(2)alpha)(2) peptide 2 and the cyclo
      (alphabeta(2)alphabeta(3)alpha)(2) peptides 3-5. The peptides 2-5 were screened
      for their ability to inhibit a small panel of Gram-negative and Gram-positive
      bacterial strains.

PMID- 23161632
TI  - When inhibitors do not inhibit: critical evaluation of rational drug design
      targeting chorismate mutase from Mycobacterium tuberculosis.
AB  - Tuberculosis (TB) is a devastating disease that claims millions of lives every
      year. Hindered access or non-compliance to medication, especially in developing
      countries, led to drug resistance, further aggravating the situation. With
      current standard therapies in use for over 50 years and only few new candidates
      in clinical trials, there is an urgent call for new TB drugs. A powerful tool for
      the development of new medication is structure-guided design, combined with
      virtual screening or docking studies. Here, we report the results of a drug
      design project, which we based on a publication that claimed the structure-guided
      discovery of several promising and highly active inhibitors targeting the
      secreted chorismate mutase (*MtCM) from Mycobacterium tuberculosis. We set out to
      further improve on these compounds and synthesized a series of new derivatives.
      Thorough evaluation of these molecules in enzymatic assays revealed, to our
      dismay, that neither the claimed lead compounds, nor any of the synthesized
      derivatives, show any inhibitory effects against *MtCM.

PMID- 23161633
TI  - Total synthesis of the peptaibols hypomurocin A3 and hypomurocin A5, and their
      conformation analysis.
AB  - The total syntheses of hypomurocin A3 and hypomuricin A5 (HM A3 and HM A5, resp.)
      in solution phase are described. These syntheses have been successfully achieved
      by applying the 'azirine/oxazolone method' to introduce the two Aib-Pro units
      into the backbone of these undecapeptaibols in one step with methyl 2,2-dimethyl
      2H-azirine-3-prolinate as the 'Aib-Pro synthon'. The coupling of Z-protected
      (Z=(benzyloxy)carbonyl) amino acids or peptide acids with amino acid tert-butyl
      esters and of peptide segments was carried out according to the TBTU (=O
      (benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate) and HOBt (=1
      hydroxybenzotriazole) protocol. Purification by reversed-phase HPLC gave the
      peptides in pure form. The products were characterized by optical rotation, NMR
      and IR spectroscopy, mass spectrometry, and elemental analysis. The crystal
      structures of HM A3 and of an octapeptide fragment of HM A5 could be obtained. An
      NMR analysis was also carried out with HM A3 and HM A5 to determine their
      conformations in solution. A global structural comparison between the three
      sequences of HM A1, HM A3, and HM A5 was performed, as well as the HPLC
      correlation of the natural HM A family and the synthetic samples.

PMID- 23161635
TI  - Synthesis of highly functionalized fluorinated cispentacin derivatives.
AB  - Fluorinated highly functionalized cispentacin derivatives were synthetised
      starting from an unsaturated bicyclic beta-lactam through C=C bond
      functionalization via the dipolar cycloaddition of a nitrile oxide, isoxazoline
      opening, and fluorination by OH/F exchange.

PMID- 23161634
TI  - Synthesis, biological evaluation, and live cell imaging of novel fluorescent
      duocarmycin analogs.
AB  - For a better understanding of the mode of action of duocarmycin and its analogs,
      the novel fluorescent duocarmycin derivatives 13-15 and 17b-19b were synthesized,
      and their bioactivity as well as their cellular uptake investigated using
      confocal laser scanning microscopy (CLSM) in live-cell imaging experiments.

PMID- 23161636
TI  - Analogs of the antituberculous agent pyrazinamide are competitive inhibitors of
      NADPH binding to M. tuberculosis fatty acid synthase I.
AB  - Analogs of pyrazinamide (=pyrazine-2-carboxamide; PZA), an essential component of
      short-course antituberculous chemotherapy, such as 5-chloropyrazinamide (5-Cl
      PZA) act as competitive inhibitors of NADPH binding to purified mycobacterial
      fatty acid synthase I (FAS I) as shown by Saturation Transfer Difference (STD)
      NMR studies. In addition, pyrazinoic acid esters (POE) and 5-Cl-POE reversibly
      bind to FAS I with the relatively greater affinity of longer-chain esters for FAS
      I, clear from the STD amplification factors. The competitive binding of PZA and 5
      Cl-PZA clearly illustrates that both agents bind FAS. In contrast to PZA, at low
      NADPH concentrations 5-Cl-PZA is a cooperative inhibitor of NADPH binding.

PMID- 23161637
TI  - Identification of the polyhydroxybutyrate granules in mammalian cultured cells.
AB  - Poly-3-hydroxybutyrate (PHB) is a biological polyester present in bacteria and
      eukaryotic cells. Long-chain (or storage) sPHB (up to 100,000 residues) is
      typically present in PHB-accumulating bacteria and localized in specialized
      granules known as carbonosomes. In these organisms, sPHB plays a major role as
      carbon and energy storage. On the other hand, short-chain (or complexed) cPHB (10
      100 residues) is present in eukaryotic organisms, including mammals as well as in
      many bacteria. Previous studies indicated that cPHB is localized in various
      subcellular compartments of the eukaryotic organisms. Here, we used fluorescent
      microscopy to directly investigate the localization of PHB in mammalian cells.
      PHB was visualized in cultured U87 cells using fluorescent probe BODIPY 493/503.
      Specificity of PHB staining was confirmed by markedly decreased fluorescence of
      samples treated with PHB-specific depolymerase (PhaZ7). We found that PHB is
      associated with granules, and that these PHB-enriched granules do not co
      localized with mitochondria, lysosomes, or endoplasmic reticulum. These results
      suggest that, in mammalian cells, PHB can accumulate in the cytoplasm in granules
      similar to 'energy storage' carbonosomes found in PHB-accumulating bacteria.

PMID- 23161638
TI  - Chlorophyll catabolites in senescent leaves of the lime tree (Tilia cordata).
AB  - In cold extracts of senescent leaves of the Lime tree (Tilia cordata), two
      colorless nonfluorescent chlorophyll catabolites (NCCs) were identified, named Tc
      NCC-1 and Tc-NCC-2, as well as a polar yellow chlorophyll catabolite (YCC), named
      Tc-YCC. The constitution of the two NCCs was determined by spectroscopic means.
      In addition, a tentative structure was derived for Tc-YCC. The three chlorophyll
      degradation products exhibited tetrapyrrolic structures, as are typical of NCCs
      or YCCs, and turned out to be rather polar, due to a glucopyranosyl group at
      their 8(2)-position. At their 3-positions, the more polar Tc-NCC-1 carried a 1,2
      dihydroxyethyl group and the less polar Tc-NCC-2 a vinyl group. Tc-YCC was
      identified as the product of an oxidation of Tc-NCC-1.

PMID- 23161639
TI  - Aryl hetaryl ketones and thioketones as efficient inhibitors of peptidyl-prolyl
      cis-trans isomerases.
AB  - A series of 18 differently substituted new aryl hetaryl ketones and thioketones
      were synthesized in four to six steps from commercial starting materials. The new
      ketones were evaluated as inhibitors of the peptidyl-prolyl cis-trans isomerase
      hPin1 with K(i)  values ranging in the one-digit micromolar to sub-micromolar
      numbers. A crystal structure revealed the non-planar arrangement of the aryl
      residues at the carbonyl compound and supports the hypothesis that the new
      compounds might mimic the transition state of the enzymatic conversion.

PMID- 23161640
TI  - An open question on the origin of life: the first forms of metabolism.
AB  - The general framework of the origin of life on Earth is outlined, emphasizing
      that the so-called prebiotic 'RNA world' is as yet on shaky scientific ground,
      and that one should any way ask the question of the structure of the first
      protocellular compartments capable of the initial forms of metabolism. This
      question is the basis of the research project on the minimal cells, containing
      the minimal and sufficient complexity capable of leading to life. Such research
      is briefly summarized, highlighting experiments with liposome-based semisynthetic
      cells which are capable of ribosomal protein synthesis with a very minimal number
      of enzymes. The most recent finding in this area of research is the unexpected
      observation that the formation and closure of liposomes in situ acts as an
      attractor for the solute molecules in solution, bringing about a very high local
      concentration in some of the liposomes. It is argued that this spontaneous
      overcrowding, which permits reactions which are not possible in the original
      dilute solution, might be the origin of cellular metabolism for the origin of
      life on Earth.

PMID- 23161641
TI  - On-resin synthesis of an acylated and fluorescence-labeled cyclic integrin ligand
      for modification of poly(lactic-co-glycolic acid).
AB  - Cyclic Arg-Gly-Asp (RGD) peptides show remarkable affinity and specificity to
      integrin receptors and mediate important physiological effects in tumor
      angiogenesis. Additionally, they are one of the keyplayers in improving the
      biocompatibility of biomaterials. The fully biodegradable polymer poly(lactic-co
      glycolic acid) (PLGA) is frequently used for biomedical implants and can be
      applied as nanoparticles for drug delivery. The aim of this work was the
      generation of a lipidated c[RGDfK] peptide including a second functionality for
      coating of hydrophobic PLGA. Therefore, we established a general and
      straightforward strategy for the introduction of two different modifications into
      the same c[RGDfK] peptide. This allowed the generation of a palmitoylated
      integrin-binding lipopeptide that shows high affinity to PLGA. Additionally, we
      coupled 5(6)-carboxyfluorescein to the second site for modification to enable
      sensitive quantification of the immobilized lipopeptide on PLGA. In conclusion,
      we present a synthesis protocol that enables the preparation of c[RGDfK]
      lipopeptides with a strong affinity to PLGA and an additional site for
      modifications. This will provide the opportunity to introduce a variety of
      effector molecules site-specifically to the c[RGDfK] lipopeptide, which will
      enable the introduction of multifunctionality into c[RGDfK]-coated PLGA devices
      or nanoparticles.

PMID- 23161643
TI  - Enamine catalysis in flow with an immobilized peptidic catalyst.
AB  - Pep talk: An immobilized peptidic catalyst achieves more than 600 turnovers in a
      continuous-flow system, allowing the production of chiral gamma-nitroaldehydes
      with excellent stereoselectivities on a scale of >450 mmol (>100 g). Such a high
      efficiency opens the way for more practical applications of enamine catalysis.

PMID- 23161644
TI  - Reservoir-based dielectrophoresis for microfluidic particle separation by charge.
AB  - The separation of particles from a complex mixture is important to a wide range
      of applications in industry, biology, medicine etc. This work demonstrates a
      microfluidic approach to separate similar-sized fluorescent and nonfluorescent
      particles based upon the difference in their surface charges inside a reservoir.
      Such a separation exploits the reservoir-based dielectrophoresis, which is
      induced by the inherent electric field gradient formed at the reservoir
      microchannel junction, to isolate the trapped fluorescent particles within the
      reservoir from the streaming nonfluorescent particles. The effects of the DC
      field magnitude (or equivalently the electrokinetic flow magnitude) and the AC
      field frequency of DC-biased AC electric fields are investigated on particle
      separation. A numerical model is also developed to simulate the electrokinetic
      transport behaviors of the two types of particles. This demonstrated reservoir
      based dielectrophoresis particle sorter can operate in parallel to increase the
      flow throughput. It is suitable for integration with other functional parts into
      lab-on-a-chip devices for diverse particle handling.

PMID- 23161645
TI  - TNFalpha antagonists for acute exacerbations of COPD: a randomised double-blind
      controlled trial.
AB  - BACKGROUND: The purpose of this randomised double-blind double-dummy placebo
      controlled trial was to investigate whether etanercept, a tumour necrosis factor
      alpha (TNFalpha) antagonist, would provide more effective anti-inflammatory
      treatment for acute exacerbations of chronic obstructive pulmonary disease (COPD)
      than prednisone. METHODS: We enrolled 81 patients with acute exacerbations of
      COPD and randomly assigned them to treatment with either 40 mg oral prednisone
      given daily for 10 days or to 50 mg etanercept given subcutaneously at
      randomisation and 1 week later. Both groups received levofloxacin for 10 days
      plus inhaled bronchodilators. The primary endpoint was the change in the
      patient's forced expiratory volume in 1 s (FEV(1)) 14 days after randomisation.
      Secondary endpoints included 90-day treatment failure rates and dyspnoea and
      quality of life. RESULTS: At 14 days the mean+/-SE change in FEV(1) from baseline
      was 20.1+/-5.0% and 15.2+/-5.7% for the prednisone and etanercept groups,
      respectively. The mean between-treatment difference was 4.9% (95% CI -10.3% to
      20.2%), p=0.52. Rates of treatment failure at 90 days were similar in the
      prednisone and etanercept groups (32% vs 40%, p=0.44), as were measures of
      dyspnoea and quality of life. Subgroup analysis revealed that patients with serum
      eosinophils >2% at exacerbation tended to experience fewer treatment failures if
      treated with prednisone compared with etanercept (22% vs 50%, p=0.08).
      CONCLUSIONS: Etanercept was not more effective than prednisone for treatment of
      acute exacerbations of COPD. Efficacy of prednisone was most apparent in patients
      who presented with serum eosinophils >2%. CLINICAL TRIALS: gov number NCT
      00789997.

PMID- 23161646
TI  - New horizons for diagnostics and therapeutic applications of graphene and
      graphene oxide.
AB  - Graphene, a one-atom-thick two-dimensional (2D) layer of sp(2) -bonded carbon,
      has received worldwide attention owing to its extraordinary physical and chemical
      properties. Recently, great efforts have been devoted to explore potential
      applications of graphene and its oxide in life science, especially in disease
      related diagnostics, near-Infrared (NIR) phototherapy and imaging. Here we will
      introduce recent advances and new horizons in this area, and focus on the rising
      progress on NIR photothermal therapy for cancer and Alzheimer's disease (AD),
      human telomerase detection, stem cell proliferation and differentiation on
      graphene substrate, diagnosis of cancer cell and related biomarkers,
      drug/nucleotide/peptide delivery and cell imaging, which have not been
      comprehensively reviewed. We hope to provide an outlook to the applications of
      graphene and its oxide, especially on the new horizons in this field, and inspire
      broader interests across various disciplines.

PMID- 23161647
TI  - Improved hydrothermal stability of mesoporous oxides for reactions in the aqueous
      phase.
AB  - A simple and inexpensive approach is used to coat metal oxide surfaces (SBA-15)
      with thin films of carbon. These carbon films provide improved hydrothermal
      stability to oxides, such as silica and alumina, which are not otherwise stable
      at elevated temperatures in the presence of liquid water. Furthermore, the carbon
      film changes the surface chemistry of the support.

PMID- 23161648
TI  - Derivation of a benchmark for freshwater ionic strength.
AB  - Because increased ionic strength has caused deleterious ecological changes in
      freshwater streams, thresholds for effects are needed to inform resource
      management decisions. In particular, effluents from surface coal mining raise the
      ionic strength of receiving streams. The authors developed an aquatic life
      benchmark for specific conductance as a measure of ionic strength that is
      expected to prevent the local extirpation of 95% of species from neutral to
      alkaline waters containing a mixture of dissolved ions in which the mass of SO
      (4)2- + HCO (3)- >= Cl(-). Extirpation concentrations of specific conductance
      were estimated from the presence and absence of benthic invertebrate genera from
      2,210 stream samples in West Virginia. The extirpation concentration is the 95th
      percentile of the distribution of the probability of occurrence of a genus with
      respect to specific conductance. In a region with a background of 116 uS/cm, the
      5th percentile of the species sensitivity distribution of extirpation
      concentrations for 163 genera is 300 uS/cm. Because the benchmark is not
      protective of all genera and protects against extirpation rather than reduction
      in abundance, this level may not fully protect sensitive species or higher
      quality, exceptional waters.

PMID- 23161649
TI  - Isoniazid prophylaxis started at 3-4 months of life does not prevent tuberculosis
      disease or infection in both HIV-infected and uninfected children.

PMID- 23161650
TI  - Efficient metathesis of terminal alkynes.
AB  - Now even terminal: The 2,4,6-trimethylbenzylidyne complexes
      [MesC=M{OC(CF(3))(2)Me}(3)] (M=Mo, W) were synthesized from [Mo(CO)(6)] and
      [W(CO)(6)], respectively. The molybdenum complex is an efficient catalyst for the
      metathesis of internal and terminal alkynes and also for the ring-closing
      metathesis of internal and terminal alpha,omega-diynes at room temperature and
      low catalyst concentrations.

PMID- 23161651
TI  - Comparison of gel-based phosphoproteomic approaches to analyse scarce oviductal
      epithelial cell samples.
AB  - The reversible change of the phosphorylation state of proteins regulates key
      cellular processes. In the present study, three different gel-based approaches
      were compared with regard to their applicability to quantitatively analyse the
      phosphoproteome of scarce biological material obtained ex vivo. Our results show
      that the phosphoproteome characterisation of oviductal epithelial cells isolated
      from the female reproductive tract requires affinity enrichment and pre
      electrophoretic labelling using fluorescence dyes. Using this approach, 30 MUg of
      enriched phosphoproteins proved to be sufficient for the phosphoproteome
      characterisation. In contrast, sequential fluorescence staining of 2D-separated
      total cell lysates as well as sequential staining in conjunction with a pre
      enrichment step led to detection discrepancies and excluded further analysis
      steps. Information gained from this study provides a successful approach for the
      phosphoproteome analysis of scarce samples. In addition, the cellular processes
      taking place in the female reproductive tract can be monitored ex vivo.

PMID- 23161652
TI  - A novel synergistic effect of iron depletion on antiangiogenic cancer therapy.
AB  - Iron is an essential element for both normal and cancer cells in humans.
      Treatment to reduce iron levels has been shown to suppress tumor growth in vivo.
      However, iron depletion monotherapy by iron decreased treatment has not been
      thought to be superior to ordinary chemotherapy and is not part of the standard
      therapeutic strategy for the treatment of cancer. Iron depletion is also known to
      reduce serum hemoglobin and oxygen supply to the tissue, which indicates that
      iron depletion may induce angiogenesis. Therefore, we hypothesized that iron
      depletion with antiangiogenic therapy can have a novel therapeutic effect in the
      treatment of cancer. Human nonsmall cell carcinoma cell lines A549 and H1299 were
      used in our study. An iron-deficient diet and an iron chelator were used to
      simulate an iron-depleted condition. The antitumor effects of iron depletion and
      antiangiogenic therapy were determined on A549 xenograft mice. The iron-depleted
      condition produced by an iron-deficient diet suppressed tumor growth. Tumor
      tissue from the iron-deficient diet group showed that cancer cell proliferation
      was suppressed and hypoxia was induced. Microvessel density of this group was
      increased which suggested that the iron-depleted condition induced angiogenesis.
      Bevacizumab administration had a synergetic effect on inhibiting the tumor growth
      on Day 39. An iron-depleted condition inhibited cancer cell proliferation and
      reciprocally induced angiogenesis. Bevacizumab synergistically enhanced the iron
      depleted antitumor effect. Treatment to deplete iron levels combined with anti
      angiogenic therapy could induce a novel therapeutic effect in the treatment of
      cancer.

PMID- 23161653
TI  - Crystal structure of 6-guanidinohexanoyl trypsin near the optimum pH reveals the
      acyl-enzyme intermediate to be deacylated.
AB  - The force driving the conversion from the acyl intermediate to the tetrahedral
      intermediate in the deacylation reaction of serine proteases remains unclear. The
      crystal structure of 6-guanidinohexanoyl trypsin was determined at pH 7.0, near
      the optimum reaction pH, at 1.94 A resolution. In this structure, three water
      molecules are observed around the catalytic site. One acts as a nucleophile to
      attack the acyl carbonyl carbon while the other two waters fix the position of
      the catalytic water through a hydrogen bond. When the acyl carbonyl oxygen
      oscillates thermally, the water assumes an appropriate angle to catalyze the
      deacylation.

PMID- 23161654
TI  - Proteomic analysis of mice expressing human ApoE demonstrates no differences in
      global protein solubility between APOE 3 and APOE 4 young mice.
AB  - Apolipoprotein E (ApoE) is a major lipid carrier protein. In humans, ApoE is
      expressed in three polymorphic isoforms, which are encoded by three different
      alleles APOE2, APOE3, and APOE4. In the brains of Alzheimer's disease (AD)
      patients, each one of these three allelic isoforms is found in several
      "isoelectric" protein isoforms (qPI), i.e. protein isoforms resulting from PTMs
      altering the net charge (q) of the polypeptide. AD is a complex disease in which
      multiple causes and several risk factors affect the onset and disease outcome. A
      major risk factor for AD is ApoE4; therefore, it is important to characterize the
      different ApoE qPIs. We have implemented a detergent-based method for isolation
      and quantitation of protein isoforms, and we found differences in the solubility
      of protein isoforms depending on the type of solvent used. In this manuscript, we
      describe these methods and applied them to young human-ApoE targeted replacement
      mice. Our results indicate that there are no significant differences in the
      hippocampus proteome of these mice as a function of the APOE genotype.

PMID- 23161655
TI  - Enteral feeding tubes: are insertion techniques and positioning based on
      anatomical evidence?
AB  - Patients in whom oral energy intake is insufficient for daily needs may develop
      malnutrition and its complications, such as increased infection rates, increased
      length of hospitalization, and death. Enteral feeding is beneficial for these
      patients. However, this therapy is not without complications related to the
      insertion and placement of enteral feeding tubes. This review aims to identify
      from the literature different techniques for insertion and the methods used to
      evaluate the placement of enteral feeding tubes.

PMID- 23161656
TI  - Fabrication of a magnet-assisted alignment device for the amperometric detection
      of capillary electrophoresis using a carbon nanotube/polypropylene composite
      electrode.
AB  - A magnet-assisted alignment device was designed and fabricated for the
      amperometric detection of CE. It mainly consisted of a magnet-containing
      electrode holder, a capillary-based microdisc detection electrode, a detection
      cell, and a micrometer adjuster. To demonstrate the feasibility and performance
      of the alignment device, it was used in combination with a carbon
      nanotube/polypropylene (CNT/PP) composite electrode for the determination of p
      phenylenediamine, m-aminophenol, and m-dihydroxybenzene in commercial hair dye by
      CE. The CNT-based electrode was fabricated by packing a melt mixture of CNTs and
      PP in a piece of fused silica capillary under heat, offering significantly lower
      operating potentials, substantially enhanced signal-to-noise characteristics, and
      high resistance to surface fouling. Because magnetic force was employed to move
      the detection electrode, the alignment system was significantly simplified. It is
      characterized by simple design and fabrication, high alignment reproducibility,
      reduced alignment time, and low cost. Both the alignment device and the CNT/PP
      composite electrode should find a wide range of applications in microchip CE,
      flowing injection analysis, and other microfluidic analysis systems. 

PMID- 23161657
TI  - Coupling porous sheathless interface MS with transient-ITP in neutral capillaries
      for improved sensitivity in glycopeptide analysis.
AB  - IgG antibodies are modulated in their function by the specific structure of the N
      glycans attached to their Fc (fragment crystallizable) portions. However, the
      glycosylation analysis of antigen-specific IgGs is a challenging task as antibody
      levels to a given antigen only represent a fraction of the total IgG levels.
      Here, we investigated the use of a transient-ITP (t-ITP)--MS method for highly
      sensitive IgG1 glycosylation profiling as a complementary method to a high
      throughput nano-RPLC-MS method. It was found that t-ITP-CZE using neutrally
      coated separation capillaries with a large volume injection (37% of capillary
      volume) and interfaced to MS with a sheathless porous sprayer yielded a 40-fold
      increase in sensitivity for IgG1 Fc glycopeptide analysis when compared to the
      conventional strategy. Furthermore, the glycoform profiles found with the t-ITP
      CZE strategy were comparable to those from nano-RPLC-MS. In conclusion, the use
      of the highly sensitive t-ITP-CZE-MS method will provide information on IgG Fc
      glycosylation for those samples with IgG1 concentrations below the LODs of the
      conventional method.

PMID- 23161658
TI  - Nano-Newton transverse force sensor using a vertical GaN nanowire based on the
      piezotronic effect.

PMID- 23161659
TI  - Light-addressable capsules as caged compound matrix for controlled triggering of
      cytosolic reactions.
AB  - Release me: polyelectrolyte capsules with different cargo in their cavities and
      plasmonic and magnetic nanoparticles in their walls were synthesized. Enzymatic
      reactions were triggered inside cells by light-mediated opening of two individual
      capsules containing either an enzyme or its substrate, by using photothermal
      heating. Furthermore, this technique allows controlled release of mRNA from
      capsules, thereby resulting in synthesis of green fluorescent protein (GFP).

PMID- 23161660
TI  - Grape seed proanthocyanidin extracts alleviate oxidative stress and ER stress in
      skeletal muscle of low-dose streptozotocin- and high-carbohydrate/high-fat diet
      induced diabetic rats.
AB  - Although ER stress in pancreas, liver, and adipose tissue was reported to be a
      novel event linked to the pathogenesis of type 2 diabetes mellitus, there is much
      less information on this event in skeletal muscle. Some studies indicated that
      treatment with antioxidants had beneficial effects on ER stress and diabetes.
      This study focuses on the effects of a strong antioxidant, grape seed
      proanthocyanidin extracts (GSPE), on skeletal muscle in diabetic rats induced
      with low dose streptozotocin- and a high-carbohydrate/high-fat diet. After 16 wk
      of GSPE treatment, diabetic rats showed decreased plasma glucose levels and
      insulin resistance. The efficacious effect of GSPE was manifested by the
      amelioration of muscular damage and dysfunction, as observed by histological
      examination and periodic acid Schiff staining. Concurrently, calcium overload and
      the abnormal activities of antioxidant enzymes and ATPases in diabetic muscles
      were partially reversed by GSPE treatment. GSPE also increased the activity of
      protein kinase B (a mediator of insulin's metabolic action) and partially
      alleviated severe ER stress. These findings suggest that GSPE may have auxiliary
      therapeutic potential for type 2 diabetes mellitus by decreasing oxidative stress
      and ER stress in skeletal muscle.

PMID- 23161662
TI  - Self-evolving oxidative stress with identifiable pre- and postmitochondrial
      phases in PC12 cells.
AB  - During the neurodegenerative process in several brain diseases, oxidative stress
      is known to play important roles in disease severity and evolution. Although
      early events of stress, such as increased lipid peroxidation and decreased
      superoxide dismutase, are known to characterize early onsets of these diseases,
      little is known about the events that participate in maintaining the chronic
      evolving phase influencing the disease progression in neurons. Here, we used
      differentiated PC12 cells to identify premitochondrial and postmitochondrial
      events occurring during the oxidative stress cascade leading to apoptosis. Our
      data indicate that an acute and strong oxidative impulse (500 MUM H(2)O(2), 30
      min) can induce, in this model, a 24-hr self-evolving stress, which advances from
      a premitochondrial phase characterized by lysosomes and cathepsin B and D
      translocations to cytosol and early mitochondrial membrane hyperpolarization.
      This phase lasts for about 5 hr and is followed by a postmitochondrial phase
      distinguished by mitochondrial membrane depolarization, reactive oxygen species
      increase, caspase-9 and caspase-3 activations, and apoptosis. Inhibition of
      cathepsins B and D suggests that cells can be protected at the premitochondrial
      phase of stress evolution and that new cathepsins regulators, such as
      glycosaminoglycans mimetics, can be considered as new therapeutic prototypes for
      neurodegeneration. Insofar as early oxidative stress markers have been related to
      the early onset of neurodegeneration, strategies protecting cells at the
      premitochondrial phase of oxidative stress may have important therapeutic
      applications.

PMID- 23161663
TI  - Metals and bacteria partitioning to various size particles in Ballona Creek storm
      water runoff.
AB  - Many storm water best management practice (BMP) devices function primarily by
      capturing particulate matter to take advantage of the well-documented association
      between storm water particles and pollutants. The hydrodynamic separation or
      settling methods used by most BMP devices are most effective at capturing medium
      to large particles; however, these may not be the most predominant particles
      associated with urban runoff. The present study examined particle size
      distribution in storm water runoff from an urban watershed in southern California
      and investigated the pollutant-particle associations of metals (Cu, Pb, Ni, and
      Zn) and bacteria (enterococci and Escherichia coli). During small storm events
      (<=0.7 cm rain), the highest concentration of pollutants were associated with a
      <6-um filter fraction, which accounted for 70% of the per storm contaminant mass
      but made up more than 20% of the total particle mass. The pollutant-particle
      association changed with storm size. Most pollutant mass was associated with >35
      um size particles during a 5-cm rain event. These results suggest that much of
      the contaminant load in storm water runoff will not be captured by the most
      commonly used BMP devices, because most of these devices (e.g., hydrodynamic
      separators) are unable to capture particles smaller than 75 um.

PMID- 23161664
TI  - Hypoxia-response element (HRE)-directed transcriptional regulation of the rat
      lysyl oxidase gene in response to cobalt and cadmium.
AB  - Lysyl oxidase (LO) catalyzes crosslink of collagen, elastin, and histone H1,
      stabilizing the extracellular matrix and cell nucleus. This enzyme displays dual
      functions for tumorigenesis, i.e., as a tumor suppressor inactivating the ras
      oncogene and as a tumor promoter enhancing malignant cell metastasis. To
      elucidate LO transcriptional regulation, we have cloned the 804 base pair region
      upstream of the translation start site (ATG) of the rat LO gene with the maximal
      promoter activity. Computer analysis indicated that at least four hypoxia
      response element (HRE) consensuses (5'-ACGTG-3') exist in the cloned LO promoter.
      Treatment of rat lung fibroblasts (RFL6) with CoCl2 (Co, 10-100 MUM), a chemical
      hypoxia reagent, enhanced LO mRNA expression and promoter activities.
      Overexpression of LO was associated with upregulation of hypoxia-inducible factor
      (HIF)-1alpha at mRNA levels in cobalt (Co)-treated cells. Thus, LO is a hypoxia
      responsive gene. Dominant negative-HIF-1alpha inhibited LO promoter activities
      stimulated by Co. Electrophoretic mobility shift, oligonucleotide competition,
      and in vitro translated HIF-1alpha binding assays indicated that only one HRE
      mapped at -387/-383 relative to ATG was functionally active among four
      consensuses. Site-directed mutation of this HRE significantly diminished the Co
      induced and LO promoter-directed expression of the reporter gene. Cadmium (Cd),
      an inducer of reactive oxygen species, inhibited HIF-1alpha mRNA expression and
      HIF-1alpha binding to the LO gene in Co-treated cells as revealed by RT-PCR and
      ChIP assays, respectively. Thus, modulation of the HRE activity by Co and Cd
      plays a critical role in LO gene transactivation.

PMID- 23161665
TI  - Catalytic hydrogenation of cyclic carbonates: a practical approach from CO2 and
      epoxides to methanol and diols.
AB  - Two birds with one stone: the simultaneous production of two important bulk
      chemicals, methanol and ethylene glycol, from CO(2) and ethylene oxide has been
      achieved under mild conditions by the highly efficient homogeneous catalytic
      hydrogenation of ethylene carbonate in the presence of a (PNP)Ru(II) catalyst.

PMID- 23161666
TI  - Microwave and magnetic (M(2) ) proteomics of the experimental autoimmune
      encephalomyelitis animal model of multiple sclerosis.
AB  - We hypothesized that quantitative MS/MS-based proteomics at multiple time points,
      incorporating rapid microwave and magnetic (M(2) ) sample preparation, could
      enable relative protein expression to be correlated to disease progression in the
      experimental autoimmune encephalomyelitis (EAE) animal model of multiple
      sclerosis. To test our hypothesis, microwave-assisted
      reduction/alkylation/digestion of proteins from brain tissue lysates bound to C8
      magnetic beads and microwave-assisted isobaric chemical labeling were performed
      of released peptides, in 90 s prior to unbiased proteomic analysis. Disease
      progression in EAE was assessed by scoring clinical EAE disease severity and
      confirmed by histopathologic evaluation for central nervous system inflammation.
      Decoding the expression of 283 top-ranked proteins (p <0.05) at each time point
      relative to their expression at the peak of disease, from a total of 1191
      proteins observed in four technical replicates, revealed a strong statistical
      correlation to EAE disease score, particularly for the following four proteins
      that closely mirror disease progression: 14-3-3epsilon (p = 3.4E-6); GPI (p =
      2.1E-5); PLP1 (p = 8.0E-4); PRX1 (p = 1.7E-4). These results were confirmed by
      Western blotting, signaling pathway analysis, and hierarchical clustering of EAE
      risk groups. While validation in a larger cohort is underway, we conclude that
      M(2) proteomics is a rapid method to quantify putative prognostic/predictive
      protein biomarkers and therapeutic targets of disease progression in the EAE
      animal model of multiple sclerosis.

PMID- 23161667
TI  - Starting-structure dependence of nanosecond timescale intersubstate transitions
      and reproducibility of MD-derived order parameters.
AB  - Factors affecting the accuracy of molecular dynamics (MD) simulations are
      investigated by comparing generalized order parameters for backbone NH vectors of
      the B3 immunoglobulin-binding domain of streptococcal protein G (GB3) derived
      from simulations with values obtained from NMR spin relaxation (Yao L, Grishaev
      A, Cornilescu G, Bax A, J Am Chem Soc 2010;132:4295-4309.). Choices for many
      parameters of the simulations, such as buffer volume, water model, or salt
      concentration, have only minor influences on the resulting order parameters. In
      contrast, seemingly minor conformational differences in starting structures, such
      as orientations of sidechain hydroxyl groups, resulting from applying different
      protonation algorithms to the same structure, have major effects on backbone
      dynamics. Some, but not all, of these effects are mitigated by increased sampling
      in simulations. Most discrepancies between simulated and experimental results
      occur for residues located at the ends of secondary structures and involve large
      amplitude nanosecond timescale transitions between distinct conformational
      substates. These transitions result in autocorrelation functions for bond vector
      reorientation that do not converge when calculated over individual simulation
      blocks, typically of length similar to the overall rotational diffusion time. A
      test for convergence before averaging the order parameters from different blocks
      results in better agreement between order parameters calculated from different
      sets of simulations and with NMR-derived order parameters. Thus, MD-derived order
      parameters are more strongly affected by transitions between conformational
      substates than by fluctuations within individual substates themselves, while
      conformational differences in the starting structures affect the frequency and
      scale of such transitions.

PMID- 23161668
TI  - Head and flagella subcompartmental proteomic analysis of human spermatozoa.
AB  - Subcellular proteomics not only deepens our knowledge of what proteins are
      present within cells, but also opens our understanding as to where those proteins
      reside. Given the highly differentiated, cross-linked state of spermatozoa, such
      studies have proven difficult to perform. In this study we have fractionated
      spermatozoa into two components, consisting of either the head or flagellar
      region. Following SDS-PAGE, 1 mm slices were digested and used for LC-MS/MS
      analysis. In total, 1429 proteins were identified with 721 proteins being
      exclusively found in the tail and 521 exclusively in the head. Not only is this
      the largest reported proteomic analysis of human spermatozoa, but also it has
      provided novel insights into the compartmentalization of proteins, particularly
      receptors, never previously reported to be present in this cell type.

PMID- 23161669
TI  - Pencil-drawn paper supported electrodes as simple electrochemical detectors for
      paper-based fluidic devices.
AB  - A simple procedure for preparing inexpensive paper-based three-electrode
      electrochemical cells is described here. They consist of small circular pads of
      hydrophilic paper defined by hydrophobic barriers printed on paper with wax-based
      ink. The back face of these pads is insulated by thermally laminating a
      polyethylene layer and working, reference and counter electrodes are drawn on
      paper by using commercial pencil leads. At last, a controlled volume of sample
      containing a supporting electrolyte was laid to soak in paper channels. Their
      performance was evaluated by assaying these devices as both simple cells suitable
      for recording voltammograms on static samples and low-cost detectors for flowing
      systems. Voltammetric tests, conducted by using potassium hexacyanoferrate(II) as
      model prototype, were also exploited for identifying the brand and softness of
      graphite sticks enabling paper to be marked with lines displaying the best
      conductivity. By taking advantage of the satisfactory information thus gained,
      pencil drawn electrodes were tested as amperometric detectors for the separation
      of ascorbic acid and sunset yellow, which were chosen as prototype electroactive
      analytes because they are frequently present concomitantly in several food
      matrices, such as soft drinks and fruit juices. This separation was performed by
      planar thin layer chromatography conducted on microfluidic paper-based devices
      prepared by patterning on filter paper two longitudinal hydrophobic barriers,
      once again printed with wax-based ink. Factors affecting both separation and
      electrochemical detection were examined and optimised, with best performance
      achieved by using a 20 mM acetate running buffer (pH 4.5) and by applying a
      detection potential of 0.9 V. Under these optimum conditions, the target analytes
      could be separated and detected within 6 min. The recorded peaks were well
      separated and characterized by good repeatability and fairly good sensitivity,
      thus proving that this approach is indeed suitable for rapidly assembling
      inexpensive and reliable electrochemical detectors for flow analysis systems. 

PMID- 23161670
TI  - Focal facial dermal dysplasia, type IV, is caused by mutations in CYP26C1.
AB  - Focal facial dermal dysplasia (FFDD) Type IV is a rare syndrome characterized by
      facial lesions resembling aplasia cutis in a preauricular distribution along the
      line of fusion of the maxillary and mandibular prominences. To identify the
      causative gene(s), exome sequencing was performed in a family with two affected
      siblings. Assuming autosomal recessive inheritance, two novel sequence variants
      were identified in both siblings in CYP26C1-a duplication of seven base pairs,
      which was maternally inherited, c.844_851dupCCATGCA, predicting p.Glu284fsX128
      and a missense mutation, c.1433G>A, predicting p.Arg478His, that was paternally
      inherited. The duplication predicted a frameshift mutation that led to a
      premature stop codon and premature chain termination, whereas the missense
      mutation was not functional based on its in vitro expression in mammalian cells.
      The FFDD skin lesions arise along the sites of fusion of the maxillary and
      mandibular prominences early in facial development, and Cyp26c1 was expressed
      exactly along the fusion line for these facial prominences in the first branchial
      arch in mice. Sequencing of four additional, unrelated Type IV FFDD patients and
      eight Type II or III TWIST2-negative FFDD patients revealed that three of the
      Type IV patients were homozygous for the duplication, whereas none of the Type II
      or III patients had CYP26C1 mutations. The seven base pairs duplication was
      present in 0.3% of healthy controls and 0.3% of patients with other birth
      defects. These findings suggest that the phenotypic manifestations of FFDD Type
      IV can be non-penetrant or underascertained. Thus, FFDD Type IV results from the
      loss of function mutations in CYP26C1.

PMID- 23161671
TI  - Post-transcriptional regulation of CD83 expression by AUF1 proteins.
AB  - Mature dendritic cells (DC), activated lymphocytes, mononuclear cells and
      neutrophils express CD83, a surface protein apparently necessary for effective DC
      mediated activation of naive T-cells and T-helper cells, thymic T-cell maturation
      and the regulation of B-cell activation and homeostasis. Although a defined
      ligand of CD83 remains elusive, the multiple cellular subsets expressing CD83, as
      well as its numerous potential implications in immunological processes suggest
      that CD83 plays an important regulatory role in the mammalian immune system.
      Lately, nucleocytoplasmic translocation of CD83 mRNA was shown to be mediated by
      direct interaction between the shuttle protein HuR and a novel post
      transcriptional regulatory element (PRE) located in the CD83 transcript's coding
      region. Interestingly, this interaction commits the CD83 mRNA to efficient
      nuclear export through the CRM1 protein translocation pathway. More recently, the
      cellular phosphoprotein and HuR ligand ANP32B (APRIL) was demonstrated to be
      directly involved in this intracellular transport process by linking the CD83
      mRNA:HuR ribonucleoprotein (RNP) complex with the CRM1 export receptor. Casein
      kinase II regulates this process by phosphorylating ANP32B. Here, we identify
      another RNA binding protein, AUF1 (hnRNP D) that directly interacts with CD83
      PRE. Unlike HuR:PRE binding, this interaction has no impact on intracellular
      trafficking of CD83 mRNA-containing complexes; but it does regulate translation
      of CD83 mRNA. Thus, our data shed more light on the complex process of post
      transcriptional regulation of CD83 expression. Interfering with this process may
      provide a novel strategy for inhibiting CD83, and thereby cellular immune
      activation.

PMID- 23161672
TI  - APPRIS: annotation of principal and alternative splice isoforms.
AB  - Here, we present APPRIS (http://appris.bioinfo.cnio.es), a database that houses
      annotations of human splice isoforms. APPRIS has been designed to provide value
      to manual annotations of the human genome by adding reliable protein structural
      and functional data and information from cross-species conservation. The visual
      representation of the annotations provided by APPRIS for each gene allows
      annotators and researchers alike to easily identify functional changes brought
      about by splicing events. In addition to collecting, integrating and analyzing
      reliable predictions of the effect of splicing events, APPRIS also selects a
      single reference sequence for each gene, here termed the principal isoform, based
      on the annotations of structure, function and conservation for each transcript.
      APPRIS identifies a principal isoform for 85% of the protein-coding genes in the
      GENCODE 7 release for ENSEMBL. Analysis of the APPRIS data shows that at least
      70% of the alternative (non-principal) variants would lose important functional
      or structural information relative to the principal isoform.

PMID- 23161673
TI  - Identifying protein interaction subnetworks by a bagging Markov random field
      based method.
AB  - Identification of differentially expressed subnetworks from protein-protein
      interaction (PPI) networks has become increasingly important to our global
      understanding of the molecular mechanisms that drive cancer. Several methods have
      been proposed for PPI subnetwork identification, but the dependency among network
      member genes is not explicitly considered, leaving many important hub genes
      largely unidentified. We present a new method, based on a bagging Markov random
      field (BMRF) framework, to improve subnetwork identification for mechanistic
      studies of breast cancer. The method follows a maximum a posteriori principle to
      form a novel network score that explicitly considers pairwise gene interactions
      in PPI networks, and it searches for subnetworks with maximal network scores. To
      improve their robustness across data sets, a bagging scheme based on
      bootstrapping samples is implemented to statistically select high confidence
      subnetworks. We first compared the BMRF-based method with existing methods on
      simulation data to demonstrate its improved performance. We then applied our
      method to breast cancer data to identify PPI subnetworks associated with breast
      cancer progression and/or tamoxifen resistance. The experimental results show
      that not only an improved prediction performance can be achieved by the BMRF
      approach when tested on independent data sets, but biologically meaningful
      subnetworks can also be revealed that are relevant to breast cancer and tamoxifen
      resistance.

PMID- 23161674
TI  - Voronoia4RNA--a database of atomic packing densities of RNA structures and their
      complexes.
AB  - Voronoia4RNA (http://proteinformatics.charite.de/voronoia4rna/) is a structural
      database storing precalculated atomic volumes, atomic packing densities (PDs) and
      coordinates of internal cavities for currently 1869 RNAs and RNA-protein
      complexes. Atomic PDs are a measure for van der Waals interactions. Regions of
      low PD, containing water-sized internal cavities, refer to local structure
      flexibility or compressibility. RNA molecules build up the skeleton of large
      molecular machineries such as ribosomes or form smaller flexible structures such
      as riboswitches. The wealth of structural data on RNAs and their complexes allows
      setting up representative data sets and analysis of their structural features. We
      calculated atomic PDs from atomic volumes determined by the Voronoi cell method
      and internal cavities analytically by Delaunay triangulation. Reference internal
      PD values were derived from a non-redundant sub-data set of buried atoms.
      Comparison of internal PD values shows that RNA is more tightly packed than
      proteins. Finally, the relation between structure size, resolution and internal
      PD of the Voronoia4RNA entries is discussed. RNA, protein structures and their
      complexes can be visualized by the Jmol-based viewer Provi. Variations in PD are
      depicted by a color code. Internal cavities are represented by their molecular
      boundaries or schematically as balls.

PMID- 23161676
TI  - New and continuing developments at PROSITE.
AB  - PROSITE (http://prosite.expasy.org/) consists of documentation entries describing
      protein domains, families and functional sites, as well as associated patterns
      and profiles to identify them. It is complemented by ProRule a collection of
      rules, which increases the discriminatory power of these profiles and patterns by
      providing additional information about functionally and/or structurally critical
      amino acids. PROSITE signatures, together with ProRule, are used for the
      annotation of domains and features of UniProtKB/Swiss-Prot entries. Here, we
      describe recent developments that allow users to perform whole-proteome
      annotation as well as a number of filtering options that can be combined to
      perform powerful targeted searches for biological discovery. The latest version
      of PROSITE (release 20.85, of 30 August 2012) contains 1308 patterns, 1039
      profiles and 1041 ProRules.

PMID- 23161675
TI  - ChIPBase: a database for decoding the transcriptional regulation of long non
      coding RNA and microRNA genes from ChIP-Seq data.
AB  - Long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) represent two classes of
      important non-coding RNAs in eukaryotes. Although these non-coding RNAs have been
      implicated in organismal development and in various human diseases, surprisingly
      little is known about their transcriptional regulation. Recent advances in
      chromatin immunoprecipitation with next-generation DNA sequencing (ChIP-Seq) have
      provided methods of detecting transcription factor binding sites (TFBSs) with
      unprecedented sensitivity. In this study, we describe ChIPBase
      (http://deepbase.sysu.edu.cn/chipbase/), a novel database that we have developed
      to facilitate the comprehensive annotation and discovery of transcription factor
      binding maps and transcriptional regulatory relationships of lncRNAs and miRNAs
      from ChIP-Seq data. The current release of ChIPBase includes high-throughput
      sequencing data that were generated by 543 ChIP-Seq experiments in diverse
      tissues and cell lines from six organisms. By analysing millions of TFBSs, we
      identified tens of thousands of TF-lncRNA and TF-miRNA regulatory relationships.
      Furthermore, two web-based servers were developed to annotate and discover
      transcriptional regulatory relationships of lncRNAs and miRNAs from ChIP-Seq
      data. In addition, we developed two genome browsers, deepView and genomeView, to
      provide integrated views of multidimensional data. Moreover, our web
      implementation supports diverse query types and the exploration of TFs, lncRNAs,
      miRNAs, gene ontologies and pathways.

PMID- 23161677
TI  - G4LDB: a database for discovering and studying G-quadruplex ligands.
AB  - The G-quadruplex ligands database (G4LDB, http://www.g4ldb.org) provides a unique
      collection of reported G-quadruplex ligands to streamline ligand/drug discovery
      targeting G-quadruplexes. G-quadruplexes are guanine-rich nucleic acid sequences
      in human telomeres and gene promoter regions. There is a growing recognition for
      their profound roles in a wide spectrum of diseases, such as cancer, diabetes and
      cardiovascular disease. Ligands that affect the structure and activity of G
      quadruplexes can shed light on the search for G-quadruplex-targeting drugs.
      Therefore, we built the G4LDB to (i) compile a data set covering various physical
      properties and 3D structure of G-quadruplex ligands; (ii) provide Web-based tools
      for G-quadruplex ligand design; and (iii) to facilitate the discovery of novel
      therapeutic and diagnostic agents targeting G-quadruplexes. G4LDB currently
      contains >800 G-quadruplex ligands with ~4000 activity records, which, to our
      knowledge, is the most extensive collection of its kind. It offers a user
      friendly interface that can meet a variety of data inquiries from researchers.
      For example, ligands can be searched for by name, molecular properties,
      structures, ligand activities and so on. Building on the reported data, the
      database also provides an online ligand design module that can predict ligand
      binding affinity in real time.

PMID- 23161679
TI  - miRNA repression of translation in vitro takes place during 43S ribosomal
      scanning.
AB  - microRNAs (miRNAs) regulate gene expression at multiple levels by repressing
      translation, stimulating deadenylation and inducing the premature decay of target
      messenger RNAs (mRNAs). Although the mechanism by which miRNAs repress
      translation has been widely studied, the precise step targeted and the molecular
      insights of such repression are still evasive. Here, we have used our newly
      designed in vitro system, which allows to study miRNA effect on translation
      independently of deadenylation. By using specific inhibitors of various stages of
      protein synthesis, we first show that miRNAs target exclusively the early steps
      of translation with no effect on 60S ribosomal subunit joining, elongation or
      termination. Then, by using viral proteases and IRES-driven mRNA constructs, we
      found that translational inhibition takes place during 43S ribosomal scanning and
      requires both the poly(A) binding protein and eIF4G independently from their
      physical interaction.

PMID- 23161678
TI  - Gene Ontology annotations and resources.
AB  - The Gene Ontology (GO) Consortium (GOC, http://www.geneontology.org) is a
      community-based bioinformatics resource that classifies gene product function
      through the use of structured, controlled vocabularies. Over the past year, the
      GOC has implemented several processes to increase the quantity, quality and
      specificity of GO annotations. First, the number of manual, literature-based
      annotations has grown at an increasing rate. Second, as a result of a new
      'phylogenetic annotation' process, manually reviewed, homology-based annotations
      are becoming available for a broad range of species. Third, the quality of GO
      annotations has been improved through a streamlined process for, and automated
      quality checks of, GO annotations deposited by different annotation groups.
      Fourth, the consistency and correctness of the ontology itself has increased by
      using automated reasoning tools. Finally, the GO has been expanded not only to
      cover new areas of biology through focused interaction with experts, but also to
      capture greater specificity in all areas of the ontology using tools for adding
      new combinatorial terms. The GOC works closely with other ontology developers to
      support integrated use of terminologies. The GOC supports its user community
      through the use of e-mail lists, social media and web-based resources.

PMID- 23161680
TI  - TropGeneDB, the multi-tropical crop information system updated and extended.
AB  - TropGeneDB (http://tropgenedb.cirad.fr) was created to store genetic, molecular
      and phenotypic data on tropical crop species. The most common data stored in
      TropGeneDB are molecular markers, quantitative trait loci, genetic and physical
      maps, genetic diversity, phenotypic diversity studies and information on genetic
      resources (geographic origin, parentage, collection). TropGeneDB is organized on
      a crop basis with currently nine public modules (banana, cocoa, coconut, coffee,
      cotton, oil palm, rice, rubber tree, sugarcane). Crop-specific Web consultation
      interfaces have been designed to allow quick consultations and personalized
      complex queries. TropGeneDB is a component of the South Green Bioinformatics
      Platform (http://southgreen.cirad.fr/).

PMID- 23161681
TI  - Update on activities at the Universal Protein Resource (UniProt) in 2013.
AB  - The mission of the Universal Protein Resource (UniProt) (http://www.uniprot.org)
      is to support biological research by providing a freely accessible, stable,
      comprehensive, fully classified, richly and accurately annotated protein sequence
      knowledgebase. It integrates, interprets and standardizes data from numerous
      resources to achieve the most comprehensive catalogue of protein sequences and
      functional annotation. UniProt comprises four major components, each optimized
      for different uses, the UniProt Archive, the UniProt Knowledgebase, the UniProt
      Reference Clusters and the UniProt Metagenomic and Environmental Sequence
      Database. UniProt is produced by the UniProt Consortium, which consists of groups
      from the European Bioinformatics Institute (EBI), the SIB Swiss Institute of
      Bioinformatics (SIB) and the Protein Information Resource (PIR). UniProt is
      updated and distributed every 4 weeks and can be accessed online for searches or
      downloads.

PMID- 23161682
TI  - PRGdb 2.0: towards a community-based database model for the analysis of R-genes
      in plants.
AB  - The Plant Resistance Genes database (PRGdb; http://prgdb.org) is a comprehensive
      resource on resistance genes (R-genes), a major class of genes in plant genomes
      that convey disease resistance against pathogens. Initiated in 2009, the database
      has grown more than 6-fold to recently include annotation derived from recent
      plant genome sequencing projects. Release 2.0 currently hosts useful biological
      information on a set of 112 known and 104 310 putative R-genes present in 233
      plant species and conferring resistance to 122 different pathogens. Moreover, the
      website has been completely redesigned with the implementation of Semantic
      MediaWiki technologies, which makes our repository freely accessed and easily
      edited by any scientists. To this purpose, we encourage plant biologist experts
      to join our annotation effort and share their knowledge on resistance-gene
      biology with the rest of the scientific community.

PMID- 23161683
TI  - Genome-wide study predicts promoter-G4 DNA motifs regulate selective functions in
      bacteria: radioresistance of D. radiodurans involves G4 DNA-mediated regulation.
AB  - A remarkable number of guanine-rich sequences with potential to adopt non
      canonical secondary structures called G-quadruplexes (or G4 DNA) are found within
      gene promoters. Despite growing interest, regulatory role of quadruplex DNA
      motifs in intrinsic cellular function remains poorly understood. Herein, we asked
      whether occurrence of potential G4 (PG4) DNA in promoters is associated with
      specific function(s) in bacteria. Using a normalized promoter-PG4-content
      (PG4(P)) index we analysed >60,000 promoters in 19 well-annotated species for (a)
      function class(es) and (b) gene(s) with enriched PG4(P). Unexpectedly, PG4
      associated functional classes were organism specific, suggesting that PG4 motifs
      may impart specific function to organisms. As a case study, we analysed
      radioresistance. Interestingly, unsupervised clustering using PG4(P) of 21 genes,
      crucial for radioresistance, grouped three radioresistant microorganisms
      including Deinococcus radiodurans. Based on these predictions we tested and found
      that in presence of nanomolar amounts of the intracellular quadruplex-binding
      ligand N-methyl mesoporphyrin (NMM), radioresistance of D. radiodurans was
      attenuated by ~60%. In addition, important components of the RecF recombinational
      repair pathway recA, recF, recO, recR and recQ genes were found to harbour
      promoter-PG4 motifs and were also down-regulated in presence of NMM. Together
      these results provide first evidence that radioresistance may involve G4 DNA
      mediated regulation and support the rationale that promoter-PG4s influence
      selective functions.

PMID- 23161684
TI  - DcGO: database of domain-centric ontologies on functions, phenotypes, diseases
      and more.
AB  - We present 'dcGO' (http://supfam.org/SUPERFAMILY/dcGO), a comprehensive ontology
      database for protein domains. Domains are often the functional units of proteins,
      thus instead of associating ontological terms only with full-length proteins, it
      sometimes makes more sense to associate terms with individual domains. Domain
      centric GO, 'dcGO', provides associations between ontological terms and protein
      domains at the superfamily and family levels. Some functional units consist of
      more than one domain acting together or acting at an interface between domains;
      therefore, ontological terms associated with pairs of domains, triplets and
      longer supra-domains are also provided. At the time of writing the ontologies in
      dcGO include the Gene Ontology (GO); Enzyme Commission (EC) numbers; pathways
      from UniPathway; human phenotype ontology and phenotype ontologies from five
      model organisms, including plants; anatomy ontologies from three organisms; human
      disease ontology and drugs from DrugBank. All ontological terms have
      probabilistic scores for their associations. In addition to associations to
      domains and supra-domains, the ontological terms have been transferred to
      proteins, through homology, providing annotations of >80 million sequences
      covering 2414 complete genomes, hundreds of meta-genomes, thousands of viruses
      and so forth. The dcGO database is updated fortnightly, and its website provides
      downloads, search, browse, phylogenetic context and other data-mining facilities.

PMID- 23161685
TI  - Atlas of genetics and cytogenetics in oncology and haematology in 2013.
AB  - The Atlas of Genetics and Cytogenetics in Oncology and Haematology
      (http://AtlasGeneticsOncology.org) is a peer-reviewed internet
      journal/encyclopaedia/database focused on genes implicated in cancer,
      cytogenetics and clinical entities in cancer and cancer-prone hereditary
      diseases. The main goal of the Atlas is to provide review articles that describe
      complementary topics, namely, genes, genetic abnormalities, histopathology,
      clinical diagnoses and a large iconography. This description, which was
      historically based on karyotypic abnormalities and in situ hybridization
      (fluorescence in situ hybridization) techniques, now benefits from comparative
      genomic hybridization and massive sequencing, uncovering a tremendous amount of
      genetic rearrangements. As the Atlas combines different types of information
      (genes, genetic abnormalities, histopathology, clinical diagnoses and external
      links), its content is currently unique. The Atlas is a cognitive tool for
      fundamental and clinical research and has developed into an encyclopaedic work.
      In clinical practice, it contributes to the cytogenetic diagnosis and may guide
      treatment decision making, particularly regarding rare diseases (because they are
      numerous and are frequently encountered). Readers as well as the authors of the
      Atlas are researchers and/or clinicians.

PMID- 23161686
TI  - Quaternary structure of the yeast Arc1p-aminoacyl-tRNA synthetase complex in
      solution and its compaction upon binding of tRNAs.
AB  - In the yeast Saccharomyces cerevisiae, the aminoacyl-tRNA synthetases (aaRS)
      GluRS and MetRS form a complex with the auxiliary protein cofactor Arc1p. The
      latter binds the N-terminal domains of both synthetases increasing their affinity
      for the transfer-RNA (tRNA) substrates tRNA(Met) and tRNA(Glu). Until now,
      structural information was available only on the enzymatic domains of the
      individual aaRSs but not on their complexes with associated cofactors. We have
      analysed the yeast Arc1p-complexes in solution by small-angle X-ray scattering
      (SAXS). The ternary complex of MetRS and GluRS with Arc1p, displays a peculiar
      extended star-like shape, implying possible flexibility of the complex. We
      reconstituted in vitro a pentameric complex and demonstrated by electrophoretic
      mobility shift assay that the complex is active and contains tRNA(Met) and
      tRNA(Glu), in addition to the three protein partners. SAXS reveals that binding
      of the tRNAs leads to a dramatic compaction of the pentameric complex compared to
      the ternary one. A hybrid low-resolution model of the pentameric complex is
      constructed rationalizing the compaction effect by the interactions of negatively
      charged tRNA backbones with the positively charged tRNA-binding domains of the
      synthetases.

PMID- 23161687
TI  - hnRNPL and nucleolin bind LINE-1 RNA and function as host factors to modulate
      retrotransposition.
AB  - Long INterspersed Element one (LINE-1, or L1), is a widely distributed,
      autonomous retrotransposon in mammalian genomes. During retrotransposition, L1
      RNA functions first as a dicistronic mRNA and then as a template for cDNA
      synthesis. Previously, we defined internal ribosome entry sequences (IRESs)
      upstream of both ORFs (ORF1 and ORF2) in the dicistronic mRNA encoded by mouse
      L1. Here, RNA affinity chromatography was used to isolate cellular proteins that
      bind these regions of L1 RNA. Four proteins, the heterogeneous nuclear
      ribonucleoproteins (hnRNPs) R, Q and L, and nucleolin (NCL), appeared to interact
      specifically with the ORF2 IRES. These were depleted from HeLa cells to examine
      their effects on L1 IRES-mediated translation and L1 retrotransposition. NCL
      knockdown specifically reduced the ORF2 IRES activity, L1 and L1-assisted Alu
      retrotransposition without altering L1 RNA or protein abundance. These findings
      are consistent with NCL acting as an IRES trans-acting factor (ITAF) for ORF2
      translation and hence a positive host factor for L1 retrotransposition. In
      contrast, hnRNPL knockdown dramatically increased L1 retrotransposition as well
      as L1 RNA and ORF1 protein, indicating that this cellular protein normally
      interferes with retrotransposition. Thus, hnRNPL joins a small, but growing list
      of cellular proteins that are potent negative regulators of L1
      retrotransposition.

PMID- 23161688
TI  - SwissBioisostere: a database of molecular replacements for ligand design.
AB  - The SwissBioisostere database (http://www.swissbioisostere.ch) contains
      information on molecular replacements and their performance in biochemical
      assays. It is meant to provide researchers in drug discovery projects with ideas
      for bioisosteric modifications of their current lead molecule, as well as to give
      interested scientists access to the details on particular molecular replacements.
      As of August 2012, the database contains 21,293,355 datapoints corresponding to
      5,586,462 unique replacements that have been measured in 35,039 assays against
      1948 molecular targets representing 30 target classes. The accessible data were
      created through detection of matched molecular pairs and mining bioactivity data
      in the ChEMBL database. The SwissBioisostere database is hosted by the Swiss
      Institute of Bioinformatics and available via a web-based interface.

PMID- 23161689
TI  - GeneTack database: genes with frameshifts in prokaryotic genomes and eukaryotic
      mRNA sequences.
AB  - Database annotations of prokaryotic genomes and eukaryotic mRNA sequences pay
      relatively low attention to frame transitions that disrupt protein-coding genes.
      Frame transitions (frameshifts) could be caused by sequencing errors or indel
      mutations inside protein-coding regions. Other observed frameshifts are related
      to recoding events (that evolved to control expression of some genes). Earlier,
      we have developed an algorithm and software program GeneTack for ab initio
      frameshift finding in intronless genes. Here, we describe a database (freely
      available at http://topaz.gatech.edu/GeneTack/db.html) containing genes with
      frameshifts (fs-genes) predicted by GeneTack. The database includes 206 991 fs
      genes from 1106 complete prokaryotic genomes and 45 295 frameshifts predicted in
      mRNA sequences from 100 eukaryotic genomes. The whole set of fs-genes was grouped
      into clusters based on sequence similarity between fs-proteins (conceptually
      translated fs-genes), conservation of the frameshift position and frameshift
      direction (-1, +1). The fs-genes can be retrieved by similarity search to a given
      query sequence via a web interface, by fs-gene cluster browsing, etc. Clusters of
      fs-genes are characterized with respect to their likely origin, such as
      pseudogenization, phase variation, etc. The largest clusters contain fs-genes
      with programed frameshifts (related to recoding events).

PMID- 23161690
TI  - The TP53 website: an integrative resource centre for the TP53 mutation database
      and TP53 mutant analysis.
AB  - A novel resource centre for TP53 mutations and mutants has been developed
      (http://p53.fr). TP53 gene dysfunction can be found in the majority of human
      cancer types. The potential use of TP53 mutation as a biomarker for clinical
      studies or exposome analysis has led to the publication of thousands of reports
      describing the TP53 gene status in >10,000 tumours. The UMD TP53 mutation
      database was created in 1990 and has been regularly updated. The 2012 release of
      the database has been carefully curated, and all suspicious reports have been
      eliminated. It is available either as a flat file that can be easily manipulated
      or as novel multi-platform analytical software that has been designed to analyse
      various aspects of TP53 mutations. Several tools to ascertain TP53 mutations are
      also available for download. We have developed TP53MULTLoad, a manually curated
      database providing comprehensive details on the properties of 2549 missense TP53
      mutants. More than 100,000 entries have been arranged in 39 different activity
      fields, such as change of transactivation on various promoters, apoptosis or
      growth arrest. For several hot spot mutants, multiple gain of function activities
      are also included. The database can be easily browsed via a graphical user
      interface.

PMID- 23161691
TI  - Volatility in mRNA secondary structure as a design principle for antisense.
AB  - Designing effective antisense sequences is a formidable problem. A method for
      predicting efficacious antisense holds the potential to provide fundamental
      insight into this biophysical process. More practically, such an understanding
      increases the chance of successful antisense design as well as saving
      considerable time, money and labor. The secondary structure of an mRNA molecule
      is believed to be in a constant state of flux, sampling several different
      suboptimal states. We hypothesized that particularly volatile regions might
      provide better accessibility for antisense targeting. A computational framework,
      GenAVERT was developed to evaluate this hypothesis. GenAVERT used UNAFold and
      RNAforester to generate and compare the predicted suboptimal structures of mRNA
      sequences. Subsequent analysis revealed regions that were particularly volatile
      in terms of intramolecular hydrogen bonding, and thus potentially superior
      antisense targets due to their high accessibility. Several mRNA sequences with
      known natural antisense target sites as well as artificial antisense target sites
      were evaluated. Upon comparison, antisense sequences predicted based upon the
      volatility hypothesis closely matched those of the naturally occurring antisense,
      as well as those artificial target sites that provided efficient down-regulation.
      These results suggest that this strategy may provide a powerful new approach to
      antisense design.

PMID- 23161692
TI  - SchistoDB: an updated genome resource for the three key schistosomes of humans.
AB  - The new release of SchistoDB (http://SchistoDB.net) provides a rich resource of
      genomic data for key blood flukes (genus Schistosoma) which cause disease in
      hundreds of millions of people worldwide. SchistoDB integrates whole-genome
      sequence and annotation of three species of the genus and provides enhanced
      bioinformatics analyses and data-mining tools. A simple, yet comprehensive web
      interface provided through the Strategies Web Development Kit is available for
      the mining and visualization of the data. Genomic scale data can be queried based
      on BLAST searches, annotation keywords and gene ID searches, gene ontology terms,
      sequence motifs, protein characteristics and phylogenetic relationships. Search
      strategies can be saved within a user's profile for future retrieval and may also
      be shared with other researchers using a unique web address.

PMID- 23161693
TI  - HMDB 3.0--The Human Metabolome Database in 2013.
AB  - The Human Metabolome Database (HMDB) (www.hmdb.ca) is a resource dedicated to
      providing scientists with the most current and comprehensive coverage of the
      human metabolome. Since its first release in 2007, the HMDB has been used to
      facilitate research for nearly 1000 published studies in metabolomics, clinical
      biochemistry and systems biology. The most recent release of HMDB (version 3.0)
      has been significantly expanded and enhanced over the 2009 release (version 2.0).
      In particular, the number of annotated metabolite entries has grown from 6500 to
      more than 40,000 (a 600% increase). This enormous expansion is a result of the
      inclusion of both 'detected' metabolites (those with measured concentrations or
      experimental confirmation of their existence) and 'expected' metabolites (those
      for which biochemical pathways are known or human intake/exposure is frequent but
      the compound has yet to be detected in the body). The latest release also has
      greatly increased the number of metabolites with biofluid or tissue concentration
      data, the number of compounds with reference spectra and the number of data
      fields per entry. In addition to this expansion in data quantity, new database
      visualization tools and new data content have been added or enhanced. These
      include better spectral viewing tools, more powerful chemical substructure
      searches, an improved chemical taxonomy and better, more interactive pathway
      maps. This article describes these enhancements to the HMDB, which was previously
      featured in the 2009 NAR Database Issue. (Note to referees, HMDB 3.0 will go live
      on 18 September 2012.).

PMID- 23161694
TI  - Genenames.org: the HGNC resources in 2013.
AB  - The HUGO Gene Nomenclature Committee situated at the European Bioinformatics
      Institute assigns unique symbols and names to human genes. Since 2011, the data
      within our database has expanded largely owing to an increase in naming
      pseudogenes and non-coding RNA genes, and we now have >33,500 approved symbols.
      Our gene families and groups have also increased to nearly 500, with ~45% of our
      gene entries associated to at least one family or group. We have also redesigned
      the HUGO Gene Nomenclature Committee website http://www.genenames.org creating a
      constant look and feel across the site and improving usability and readability
      for our users. The site provides a public access portal to our database with no
      restrictions imposed on access or the use of the data. Within this article, we
      review our online resources and data with particular emphasis on the updates to
      our website.

PMID- 23161695
TI  - eProS--a database and toolbox for investigating protein sequence-structure
      function relationships through energy profiles.
AB  - Gaining information about structural and functional features of newly identified
      proteins is often a difficult task. This information is crucial for understanding
      sequence-structure-function relationships of target proteins and, thus, essential
      in comprehending the mechanisms and dynamics of the molecular systems of
      interest. Using protein energy profiles is a novel approach that can contribute
      in addressing such problems. An energy profile corresponds to the sequence of
      energy values that are derived from a coarse-grained energy model. Energy
      profiles can be computed from protein structures or predicted from sequences. As
      shown, correspondences and dissimilarities in energy profiles can be applied for
      investigations of protein mechanics and dynamics. We developed eProS (energy
      profile suite, freely available at http://bioservices.hs-mittweida.de/Epros/), a
      database that provides ~76 000 pre-calculated energy profiles as well as a
      toolbox for addressing numerous problems of structure biology. Energy profiles
      can be browsed, visualized, calculated from an uploaded structure or predicted
      from sequence. Furthermore, it is possible to align energy profiles of interest
      or compare them with all entries in the eProS database to identify significantly
      similar energy profiles and, thus, possibly relevant structural and functional
      relationships. Additionally, annotations and cross-links from numerous sources
      provide a broad view of potential biological correspondences.

PMID- 23161697
TI  - Micellar ordered structure effects on high-resolution CE-SSCP using Pluronic
      triblock copolymer blends.
AB  - Pluronic F108 block copolymers have shown a great promise to achieve the
      desirable high resolution in the conformation-sensitive separation of ssDNA using
      CE-SSCP. However, fundamental understanding of the structures and properties of
      Pluronic matrix affecting the resolution is still limited. Unlike conventional
      gel-forming homopolymers, Pluronic F108 block copolymers are amphiphilic
      macromolecules consisting of poly(ethylene oxide)-b-poly(propylene oxide)-b
      poly(ethylene oxide) triblock copolymers, which are capable of forming a highly
      ordered micellar structure in aqueous solution. In this study, we have performed
      a series of experiments by blending different types of Pluronic polymers to
      control the formation of micelles and to study the correlation between separation
      and rheological characteristics of Pluronic gels affecting the resolution of CE
      SSCP. Our experiments have been specifically designed to elucidate how the
      micellar structure affects the resolution of CE-SSCP upon altering the size
      uniformity and constituent homogeneity of the micelles. Our results suggest that
      uniformly sized micelle packing is the primary structural feature of Pluronic gel
      matrix for the high-resolution separation, while the size and constituent of the
      micelle themselves need to be considered as secondary factors.

PMID- 23161696
TI  - Contribution of intersubunit bridges to the energy barrier of ribosomal
      translocation.
AB  - In every round of translation elongation, EF-G catalyzes translocation, the
      movement of tRNAs (and paired codons) to their adjacent binding sites in the
      ribosome. Previous kinetic studies have shown that the rate of tRNA-mRNA movement
      is limited by a conformational change in the ribosome termed 'unlocking'.
      Although structural studies offer some clues as to what unlocking might entail,
      the molecular basis of this conformational change remains an open question. In
      this study, the contribution of intersubunit bridges to the energy barrier of
      translocation was systematically investigated. Unlike those targeting B2a and B3,
      mutations that disrupt bridges B1a, B4, B7a and B8 increased the maximal rate of
      both forward (EF-G dependent) and reverse (spontaneous) translocation. As bridge
      B1a is predicted to constrain 30S head movement and B4, B7a and B8 are predicted
      to constrain intersubunit rotation, these data provide evidence that formation of
      the unlocked (transition) state involves both 30S head movement and intersubunit
      rotation.

PMID- 23161698
TI  - Bilayered Raman-intense gold nanostructures with hidden tags (BRIGHTs) for high
      resolution bioimaging.
AB  - Conventional SERS probes suffer from limited brightness and poor reproducibility
      and stability making them unsuitable for routine in vivo applications. A novel
      class of layered SERS probes is demonstrated in which individual nanostructures
      host electromagnetic hotspots, thus increasing brightness by more than two orders
      magnitude compared to conventional individual nanostructures.

PMID- 23161699
TI  - Side-on coordinated distannene: an unprecedented nickel(0) complex.

PMID- 23161700
TI  - Oriented molecular attachments through sol-gel chemistry for synthesis of
      ultrathin hydrated vanadium pentoxide nanosheets and their applications.
AB  - Ultrathin single-crystalline V2 O5 .0.76H2 O nanosheets with a thickness of 1.5
      2.6 nm are prepared on the basis of molecular-level 'oriented attachment' through
      special sol-gel chemistry. The initial formation of 3-7 nm nanodiscs by confining
      the condensation reactions within the ab plane is critical to form nanosheets. As
      a proof-of-concept, these nanosheets exhibit good properties for hydrogen sensors
      and supercapacitors.

PMID- 23161701
TI  - Recurrent missense mutations in TMEM43 (ARVD5) due to founder effects cause
      arrhythmogenic cardiomyopathies in the UK and Canada.
AB  - AIMS: Autosomal dominant arrhythmogenic right ventricular
      cardiomyopathy/dysplasia (ARVC/D) (in the group of arrhythmogenic
      cardiomyopathies) is a common cause of sudden cardiac death in young adults. It
      is both clinically and genetically heterogeneous, with 12 loci (ARVC/D1-12) and
      eight genes identified, the majority of which encode structural proteins of
      cardiac desmosomes. The most recent gene identified, TMEM43, causes disease due
      to a missense mutation in a non-desmosomal gene (p.S358L) in 15 extended families
      from Newfoundland, Canada. To determine whether mutations in TMEM43 cause ARVC/D
      and arrhythmogenic cardiomyopathy in other populations, we fully re-sequenced
      TMEM43 on 143 ARVC/D probands (families) from the UK and 55 probands (from 55
      families) from Newfoundland. METHODS AND RESULTS: Bidirectional sequencing of
      TMEM43 including intron-exon boundaries revealed 33 variants, the majority
      located in non-coding regions of TMEM43. For the purpose of validation, families
      of probands with rare, potentially deleterious coding variants were subjected to
      clinical and molecular follow-up. Three missense variants of uncertain
      significance (p.R28W, p.E142K, p.R312W) were located in highly conserved regions
      of the TMEM43 protein. One variant (p.R312W) also co-segregated with relatives
      showing clinical signs of disease. Genotyping and expansion of the disease
      associated haplotype in subjects with the p.R312W variant from Newfoundland,
      Canada, and the UK suggest common ancestry. CONCLUSION: Although the p.R312W
      variant was found in controls (3/378), identification of an ancestral disease p
      R312W haplotype suggests that the p.R312W variant is a pathogenic founder
      mutation.

PMID- 23161702
TI  - Epicardial substrate mapping for ventricular tachycardia ablation in patients
      with non-ischaemic cardiomyopathy: a new algorithm to differentiate between scar
      and viable myocardium developed by simultaneous integration of computed
      tomography and contrast-enhanced magnetic resonance imaging.
AB  - AIMS: During epicardial electroanatomical mapping (EAM), it is difficult to
      differentiate between fibrosis and fat, as both exhibit attenuated bipolar
      voltage (BV). The purpose of this study was to assess whether unipolar voltage
      (UV), BV, and electrogram characteristics (EC) can distinguish fibrosis from
      viable myocardium and fat during epicardial EAM for ventricular tachycardia (VT)
      ablation in non-ischaemic cardiomyopathy (NICM). METHODS AND RESULTS: Ten NICM
      patients (7 males, 56 +/- 13 years) with VT underwent epicardial EAM with real
      time integration of computed tomography-derived epicardial fat and contrast
      enhanced MRI-derived scar. Bipolar voltage (filtered 30-400 Hz), UV (filtered 1
      240 Hz), and EC (duration and morphology) were correlated with the presence of
      fat and scar. At sites devoid of fat, the optimal cutoff values to differentiate
      between scar and myocardium were 1.81 mV for BV and 7.95 mV for UV. Bipolar
      voltage, UV, and electrogram duration >50 ms distinguished scar from myocardium
      in areas covered with <2.8 mm fat (all P < 0.001), but not >= 2.8 mm fat. In
      contrast, electrogram morphology-characteristics could also detect scar covered
      with >= 2.8 mm fat (P = 0.001). A newly developed three-step algorithm combining
      electrogram morphology, duration, and UV could correctly identify scar with a
      sensitivity of 75%. Unipolar voltage but not BV could detect intramural scar in
      the absence of fat. CONCLUSIONS: Both BV <= 1.81 mV and UV <= 7.95 mV are useful
      for detection of scar during epicardial EAM, in the absence of >= 2.8 mm fat.
      However, EC can be used to detect scar covered with fat. A newly developed
      algorithm combining UV and EC can differentiate between scar and viable
      myocardium. Unipolar voltage but not BV could detect intramural scar.

PMID- 23161703
TI  - Influence of 23 coronary artery disease variants on recurrent myocardial
      infarction or cardiac death: the GRACE Genetics Study.
AB  - AIMS: A pooled analysis of 14 genome-wide association studies revealed 23
      susceptibility loci for coronary artery disease (CAD), thereby providing the most
      comprehensive genetic blueprint of CAD susceptibility. Here, we evaluated whether
      these 23 loci also predispose to recurrent myocardial infarction (MI) or cardiac
      death following an acute coronary syndrome (ACS). METHODS AND RESULTS: A total of
      2099 ACS patients enrolled in the Global Registry of Acute Coronary Events
      (GRACE) UK-Belgian study were prospectively followed for a median of 5 years
      (1668 days). C-allele carriers of the rs579459 variant, which is located upstream
      of the ABO gene and correlates with blood group A, were independently associated
      with recurrent MI [multivariable-adjusted hazard ratio (HR) 2.25, CI = 1.37-3.71;
      P = 0.001] and with recurrent MI or cardiac death [multivariable-adjusted (HR)
      1.80, CI = 1.09-2.95; P = 0.021] within 5 years after an index ACS. The
      association of rs579459 was replicated in 1250 Polish patients with 6 months
      follow-up after an index ACS [multivariable-adjusted (HR) 2.70, CI = 1.26-5.82; P
      = 0.011 for recurrent MI]. Addition of rs579459 to a prediction model of 17
      clinical risk factors improved risk classification for recurrent MI or cardiac
      death at 6 months as calculated by the integrated discrimination improvement
      method (P = 0.037), but not by C-statistics (P = 0.096). CONCLUSION: In this
      observational study, rs579459 was independently associated with adverse cardiac
      outcome after ACS. A weak improvement in clinical risk prediction was also
      observed, suggesting that rs579459 should be further tested as a potentially
      relevant contributor to risk prediction models for adverse outcome following ACS.

PMID- 23161704
TI  - Directed assembly of inorganic polyoxometalate-based micrometer-scale tubular
      architectures by using optical control.

PMID- 23161705
TI  - N-methyl-D-aspartate receptor-mediated axonal injury in adult rat corpus
      callosum.
AB  - Damage to white matter such as corpus callosum (CC) is a pathological
      characteristic in many brain disorders. Glutamate (Glut) excitotoxicity through
      AMPA receptors on oligodendrocyte (OL) was previously considered as a mechanism
      for white matter damage. Recent studies have shown that N-methyl-D-aspartate
      receptors (NMDARs) are expressed on myelin sheath of neonatal rat OL processes
      and that activation of these receptors mediated demyelization. Whether NMDARs are
      expressed in the adult CC and are involved in excitotoxic axonal injury remains
      to be determined. In this study, we demonstrate the presence of NMDARs in the
      adult rat CC and their distributions in myelinated nerve fibers and OL somata by
      means of immunocytochemical staining and Western blot. Incubation of the CC
      slices with Glut or NMDA induced axonal injury as revealed by analyzing amplitude
      of CC fiber compound action potentials (CAPs) and input-output response. Both
      Glut and NMDA decreased the CAP amplitude and input-output responses, suggesting
      an involvement of NMDARs in Glut- and NMDA-induced axonal injury. The involvement
      of NMDAR in Glut-induced axonal injury was further assayed by detection of beta
      amyloid precursor protein (beta-APP) in the CC axonal fibers. Treatment of the CC
      slices with Glut resulted in beta-APP accumulation in the CC fibers as detected
      by Western blot, reflecting an impairment of axonal transport function. This
      injurious effect of Glut on CC axonal transport was significantly blocked by
      MK801. Taken together, these results show that NMDARs are expressed in the adult
      CC and are involved in excitotoxic activity in adult CC slices in vitro.

PMID- 23161706
TI  - Use of a novel sediment exposure to determine the effects of triclosan on
      estuarine benthic communities.
AB  - Triclosan (5-chloro-2-[2,4-dichlorophenoxy]phenol) is a relatively new, commonly
      used antimicrobial compound found in many personal care products. Triclosan is
      toxic to marine organisms at the micrograms per liter level, can photodegrade to
      a dioxin, can accumulate in humans, and has been found to be stable in marine
      sediments for over 30 years. To determine the effects of triclosan on marine
      benthic communities, intact sediment cores were brought into the laboratory and
      held under flowing seawater conditions. A 2-cm layer of triclosan-spiked sediment
      was applied to the surface, and after a two-week exposure the meio- and
      macrofaunal communities were assessed for differences in composition relative to
      nonspiked cores. A high triclosan treatment (180 mg/kg dry wt) affected both the
      meio- and the macrobenthic communities. There were no discernible differences
      with a low-triclosan treatment (14 mg/kg dry wt). This exposure method is
      effective for testing the benthic community response to sediment contaminants,
      but improvements should be made with regard to the amount and method of applying
      the overlying sediment to prevent smothering of fragile benthic organisms.

PMID- 23161707
TI  - Fabrication and characterization of nanopores with insulated transverse
      nanoelectrodes for DNA sensing in salt solution.
AB  - We report on the fabrication, simulation, and characterization of insulated
      nanoelectrodes aligned with nanopores in low-capacitance silicon nitride membrane
      chips. We are exploring these devices for the transverse sensing of DNA molecules
      as they are electrophoretically driven through the nanopore in a linear fashion.
      While we are currently working with relatively large nanopores (6-12 nm in
      diameter) to demonstrate the transverse detection of DNA, our ultimate goal is to
      reduce the size sufficiently to resolve individual nucleotide bases, thus
      sequencing DNA as it passes through the pore. We present simulations and
      experiments that study the impact of insulating these electrodes, which is
      important to localize the sensing region. We test whether the presence of
      nanoelectrodes or insulation affects the stability of the ionic current flowing
      through the nanopore, or the characteristics of DNA translocation. Finally, we
      summarize the common device failures and challenges encountered during
      fabrication and experiments, explore the causes of these failures, and make
      suggestions on how to overcome them in the future.

PMID- 23161708
TI  - Are we insane? Observations on the idea of gynecologic screening cytology
      "productivity".

PMID- 23161709
TI  - Molecular pathology of breast cancer: what a pathologist needs to know.
AB  - Pathologists are now more than ever "diagnostic oncologists" and serve a critical
      role as clinical consultants on the biology of disease. In the last decade and a
      half, molecular information has transformed our thinking about the biologic
      diversity of breast cancers and redirected the way clinical treatment decisions
      are made. A basic understanding of the current molecular classification of breast
      cancers and the biologic pathways from precursors to invasive disease is key to
      both informing diagnostic practice and serving as clinical consultants. In
      addition, both single-marker and panel-based molecular tests are currently being
      utilized in breast cancer tissue to predict the benefit of specific therapies
      such as HER2-targeted biologic therapy and chemotherapy. Familiarity with the
      current issues involving these molecular tests as well as the pathologist's role
      in ensuring appropriate tissue handling, tissue selection, and results
      interpretation and correlation are paramount to providing optimal patient care.

PMID- 23161710
TI  - Mucocele-like lesions diagnosed on breast core biopsy: assessment of upgrade rate
      and need for surgical excision.
AB  - Mucocele-like lesion (MLL) is a rare mucinous lesion of the breast with highly
      variable upgrade rates to atypia or malignancy on excision. This spectrum of data
      has led to differing opinions on the need for surgical excision. We evaluated 50
      core biopsy specimens diagnosed as having MLLs and correlated the findings with
      those of excision pathology. Thirty-eight patients underwent surgical excision
      and 29 were benign (76%), 4 had atypical ductal hyperplasia (11%), and 5 had
      ductal carcinoma in situ (13%), with an overall upgrade rate of 13%. However, the
      risk of upgrade was exclusively associated with the presence of atypia as seen on
      the needle core biopsy. All 22 MLLs without atypia had benign excisions, while 5
      (31%) of the 16 patients with MLLs with atypia were upgraded to ductal carcinoma
      in situ on excision. No invasive carcinoma was identified. We believe it is
      reasonable that women with the core biopsy diagnosis of MLL without atypia and no
      associated mass be offered close clinical follow-up as an alternative to surgery.

PMID- 23161711
TI  - Microcalcification is an important factor in the management of breast intraductal
      papillomas diagnosed on core biopsy.
AB  - The follow-up excision (FUE) results were analyzed from 370 cases diagnosed as
      intraductal papilloma on breast core needle biopsy (CNB) with no history of
      malignancy or other risk factors. Of these cases, 98.6% were rendered a Breast
      Imaging Reporting and Data System score of 4 on mammography before the CNB. Fifty
      one cases (13.8%) were found to have microcalcifications on microscopic
      examination of CNB. A total of 7 (1.9%) of 370 cases were upgraded to invasive
      carcinoma, ductal carcinoma in situ, or pleomorphic lobular carcinoma in situ on
      FUE. Six of 51 (11.8%) cases with microcalcifications found on imaging and CNB
      were upgraded to ductal carcinoma in situ or invasive carcinoma, whereas only 1
      (0.3%) of 319 cases without microcalcifications was upgraded to pleomorphic
      lobular carcinoma in situ (P = .003). Results of a multivariate analysis adjusted
      for age confirmed that microcalcifications was a risk factor for upgrading to
      cancer, independent of age. Our results indicate that surgical excision is
      required for intraductal papilloma diagnosed on CNB if microcalcifications are
      present. However, excision may not be required for those who have no
      microcalcifications on CNB and no other known risk factors.

PMID- 23161712
TI  - Interobserver agreement among pathologists for semiquantitative hormone receptor
      scoring in breast carcinoma.
AB  - The American Society of Clinical Oncology/College of American Pathologists
      (ASCO/CAP) guidelines recommend reporting of hormone receptor test results in a
      semiquantitative manner. This study used 74 resected estrogen receptor (ER)
      positive invasive breast cancers to determine reproducibility of semiquantitative
      scoring of hormone receptors using the H-score method. Four pathologists
      independently scored each slide. Agreement among observers was analyzed via
      Fleiss kappa statistics on ER and progesterone receptor (PR) categorical scores.
      Intraclass correlation coefficient (ICC) was used to estimate the interobserver
      agreement for ER and PR H-scores on a continuous scale (0-300). There was 100%
      agreement for categorical ER results (kappa = 1) and 97% agreement (kappa =
      0.823, P < .001) for categorical PR results. For quantitative H-scores, ICC
      agreement was 0.85 (95% confidence interval [CI] = 0.79-0.90) for ER and 0.87
      (95% CI = 0.82-0.92) for PR. Because the H-score provides a continuous measure of
      tumor hormone receptor content, we suggest universal adoption of this method.

PMID- 23161713
TI  - ERG protein expression in human tumors detected with a rabbit monoclonal
      antibody.
AB  - Avian v-ets erythroblastosis virus E26 oncogene homolog (ERG) is highly sensitive
      and specific for endothelial neoplasms and specific for prostate carcinoma. We
      characterized a rabbit anti-ERG antibody as an immunohistochemical agent to
      detect ERG expression in various tumors using tissue microarrays with a wide
      array of epithelial and mesenchymal tumors. ERG was positive in 63 (38%) of 168
      prostate carcinomas and negative in all other epithelial tumors. ERG was positive
      in all 125 vascular lesions. It was also positive in the sarcomatoid component of
      a high-grade urothelial carcinoma and 6 (40%) of 15 meningiomas. Twelve (80%) of
      15 meningiomas were positive for Fli1, including all 6 ERG-positive cases.
      Positive immunostaining with this antibody is therefore highly specific for
      prostate carcinoma and vascular lesions, with a few caveats. ERG is rarely
      detected in nonvascular mesenchymal tumors with this antibody. Furthermore, about
      40% of meningiomas are also positive for ERG immunohistochemically, probably
      because of cross-reactivity with Fli1.

PMID- 23161714
TI  - Increasing cytotechnologist workload above 100 slides per day using the BD
      FocalPoint GS imaging system negatively affects screening performance.
AB  - Studies examining the effects of increased workload on the performance of
      individual cytotechnologists are limited. Using FocalPoint GS, the performance of
      3 cytotechnologists was evaluated. The study consisted of 3 phases. In phase I,
      cytotechnologists were asked to screen at their usual pace. In phase II,
      cytotechnologists were asked to screen as fast as possible without feeling that
      the quality of their work was diminished. In phase III, cytotechnologists were
      asked to screen at least 15% more than their daily workload from phase II.
      Productivity was increased by decreasing the percentage of cases that underwent
      full manual review (from 38% to 19%) and by decreasing the time spent on each
      slide (from 5.5 min to 3.7 min). Overall, the total abnormal rate decreased by
      31.9% from phase I to phase III of the study. In addition, the false-negative
      fraction increased significantly, from 1% to 6.9%. Our results indicated a
      negative association between increased cytotechnologist daily workload with
      FocalPoint GS and CT screening performance. Workloads were increased by
      decreasing the time spent reviewing 10 fields of view and the percentage of cases
      that underwent full manual review.

PMID- 23161715
TI  - Thymic hyperplasia with lymphoepithelial sialadenitis (LESA)-like features: a
      clinicopathologic and immunohistochemical study of 4 cases.
AB  - Four cases of an unusual type of thymic hyperplasia strongly resembling
      lymphoepithelial sialadenitis (LESA) of the salivary glands are described. The
      patients were 2 men and 2 women aged 37 to 53 years. On histologic examination,
      abundant lymphoid tissue with lymphoid follicles containing germinal centers and
      areas of plasma cell infiltration were seen. The epithelial component consisted
      of a proliferation of Hassall corpuscles and islands of thymic epithelial cells.
      Cystic changes and lymphoepithelial lesions were identified in all cases, but a
      monocytoid B-cell population was absent. On immunohistochemical examination, a
      mixed B- and T-cell population was identified, and polymerase chain reaction
      performed in 1 case showed polyclonality. Follow-up revealed that all patients
      were alive 5 months to 9 years after diagnosis. The cases in this series
      represent a distinct type of thymic hyperplasia that histologically strongly
      resembles LESA. The clinicopathologic and immunohistochemical features are
      presented, and a possible relationship with thymic mucosa-associated lymphoid
      tissue (MALT) lymphoma is discussed.

PMID- 23161716
TI  - The comparative effectiveness of fine-needle aspiration cytology sampling
      policies: a simulation study.
AB  - Sample adequacy is an important aspect of overall fine-needle aspiration cytology
      (FNAC) performance. FNAC effectiveness is augmented by an increasing number of
      needle passes, but increased needle passes are associated with higher costs and
      greater risk of adverse events. The objective of this study was to compare the
      impact of several different sampling policies on FNAC effectiveness and adverse
      event rates using discrete event simulation. We compared 8 different sampling
      policies in 12 different sampling environments. All sampling policies were
      effective when the per-pass accuracy is high (>80%). Rapid on-site evaluation
      (ROSE) improves FNAC effectiveness when the per-pass adequacy rate is low. ROSE
      is unlikely to be cost-effective in sampling environments in which the per-pass
      adequacy is high. Alternative ROSE assessors (eg, cytotechnologists) may be a
      cost-effective alternative to pathologists when the per-pass adequacy rate is
      moderate (60%-80%) or when the number of needle passes is limited.

PMID- 23161717
TI  - Analysis of immunohistochemical stain usage in different pathology practice
      settings.
AB  - This study compares the use of immunohistochemistry (IHC) for diagnosing
      carcinoma in private practice and commercial settings with use in a single
      academic center. H&E-stained slides and IHC stains, when present, of recently
      diagnosed carcinomas (n = 200) from patients referred to our institution for
      treatment were reviewed by a resident and mid-and senior-level pathologists.
      Diagnostic agreement between academic and referral pathologists was 98%; the
      former group used IHC stains in 11% and the latter in 26% of cases (P < .0001).
      Pathologists from commercial laboratories (12% of referrals) used IHC in 38% of
      cases, whereas private/hospital-based community laboratories (86% of referrals)
      used them in 24%. The average number of stains ordered per case was similar among
      all groups. We suggest that the use of IHC may reflect both the degree of
      experience of the pathologist and the pathology practice setting.

PMID- 23161718
TI  - Simultaneous analysis of HER2 gene and protein on a single slide facilitates HER2
      testing of breast and gastric carcinomas.
AB  - This study sought to evaluate a new combined gene and protein detection platform
      in the context of HER2 evaluation in breast and gastric carcinomas. HER2
      immunohistochemistry (IHC) and dual color in situ hybridization (Dual ISH) were
      combined on a single slide. Results were compared with conventional HER2 IHC and
      fluorescence ISH. Results from the gene and protein assay were reliable and
      highly reproducible for both breast and gastric carcinomas. Concordance was found
      between conventional HER2 IHC and ISH testing and the gene and protein assay in
      the same laboratory (>95% for Dual ISH; lower for IHC because of different
      antibody clones), between IHC and Dual ISH performed on the same slide (>92%),
      and in the gene and protein assays between laboratories (>96%). This cost- and
      time-effective method provides fast and definitive results (IHC confirmed by
      means of Dual ISH) to aid in rapid treatment decisions. It can also be applied to
      other gene and protein combinations.

PMID- 23161719
TI  - Prognostic significance of the ratio of absolute neutrophil count to absolute
      lymphocyte count in classic Hodgkin lymphoma.
AB  - The aim of this study was to determine the prognostic effect of the absolute
      neutrophil count/absolute lymphocyte count ratio (ANC/ALC ratio) in patients with
      classic Hodgkin lymphoma (cHL). We performed a retrospective analysis of 312
      patients with cHL. Univariate analysis revealed that a high ANC/ALC ratio (>=4.3)
      correlated with poor overall survival (OS) (P < .001). Subgroup analysis of
      advanced-stage disease showed that the ANC/ALC ratio was significant for OS (P =
      .032). Multivariate analysis revealed the ANC/ALC ratio to be an independent
      prognostic factor for OS (P = .048). The ANC/ALC ratio allowed further risk
      stratification in patients who were considered to be at low risk on the basis of
      an International Prognostic Score less than 4 (P = .002). The ANC/ALC ratio is a
      simple, inexpensive, and independent prognostic factor for OS that may improve
      the ability to identify high-risk patients with cHL.

PMID- 23161720
TI  - Myeloid neoplasms secondary to plasma cell myeloma: an intrinsic predisposition
      or therapy-related phenomenon? A clinicopathologic study of 41 cases and
      correlation of cytogenetic features with treatment regimens.
AB  - We describe 41 cases of myeloid neoplasms (MNs) secondary to plasma cell myeloma
      (PCM). The types of MN included myelodysplastic syndrome (MDS) in 34 (82.9%),
      acute myeloid leukemia (AML) in 4 (9.8%), and myeloproliferative neoplasm (MPN)
      or MDS/MPN in 3 (7.3%) cases. The latency from treatment to diagnosis of MN
      ranged from 9 to 384 months, with a median of 60 months. Of 37 cases with
      cytogenetic studies, complex abnormalities were detected in 22 (59.5%), -5(q)/
      7(q) in 4 (10.8%), other abnormalities in 8 (21.6%), and normal karyotype in 3
      (8.1%) cases. Complex abnormalities and -5(q)/-7(q) correlated directly with
      multiple chemotherapeutic regimens, particularly with combined
      melphalan/cyclophosphamide. Moreover, the features of cytogenetic abnormalities
      in our series were significantly different from those with concomitant PCM/MN who
      had significantly lower complex abnormalities. The latency, skewed proportion of
      MDS, and bias toward complex cytogenetic abnormalities/unbalanced aberrations of
      chromosomes 5/7 suggested an alkylating mutagenic effect on pathogenesis of
      secondary MN. Kaplan-Meier survival analysis demonstrated a median survival of 19
      months, which was better than that for therapy-related (t)-MDS/AML. In contrast
      to t-MDS, the survival in our patients appeared to depend on subtypes of MDS as
      seen in de novo diseases.

PMID- 23161721
TI  - CD200 expression in plasma cells of nonmyeloma immunoproliferative disorders:
      clinicopathologic features and comparison with plasma cell myeloma.
AB  - The majority of plasma cell myelomas (PCMs) are positive for CD200, a membrane
      protein with immunosuppressive function. There are no flow cytometry data in the
      literature on plasma cell CD200 expression in other immunoproliferative
      disorders. Therefore we used flow cytometry to study the expression of CD200 on
      plasma cells in diagnostic bone marrow aspirates from 61 patients with monoclonal
      gammopathy of undetermined significance (MGUS) and 10 patients with
      lymphoplasmacytic lymphoma (LPL). For comparison, we evaluated CD200 expression
      in 74 PCM bone marrow biopsies. Thirty-three (54.1%) of 61 MGUS cases and 2
      (20.0%) of 10 LPL cases were CD200+. Comparative clinicopathologic parameters for
      MGUS cases, based on CD200 expression status, showed no differences between the 2
      groups. The proportion of CD200+ PCMs (73.0%) in our series was significantly
      higher than that of CD200+ MGUS (P = .030) and CD200+ LPL (P = .002) cases.

PMID- 23161722
TI  - Investigation of the BRAF V600E mutation by pyrosequencing in lymphoproliferative
      disorders.
AB  - The presence of the BRAF c.1799T>A V600E mutation was recently described in cases
      of hairy cell leukemia (HCL) but not in other common lymphomas. However, many
      uncommon subtypes of lymphoma have not been studied. We designed a BRAF
      pyrosequencing assay specific for the V600E mutation, which has a sensitivity of
      5% and is applicable to paraffin-embedded tissue. DNA was sequenced in 9 cases of
      HCL; 6 cases of variant HCL; 10 cases each of nodal marginal zone lymphoma
      (NMZL), extranodal marginal zone lymphoma (ENMZL), posttransplantation
      lymphoproliferative disorder (PTLD), and large granular lymphocyte (LGL)
      proliferations; 11 cases of peripheral T-cell lymphoma (PTCL); and 12 cases of
      anaplastic large cell lymphoma (ALCL). All (100%) cases of HCL were positive for
      BRAF mutations. No mutations were identified in variant HCL, NMZL, ENMZL, PTLD,
      PTCL, ALCL, or LGL proliferations. Among lymphoproliferative disorders, BRAF
      mutations are restricted to HCL.

PMID- 23161723
TI  - CDX2 Expression in Some Variants of Papillary Thyroid Carcinoma.

PMID- 23161724
TI  - Transient serum exposure regimes to support dual differentiation of human
      mesenchymal stem cells.
AB  - Human mesenchymal stem cells (MSCs), which can generate both osteoblasts and
      chondrocytes, represent an ideal resource for orthopaedic repair using tissue
      engineering approaches. One major difficulty for the development of osteochondral
      constructs using undifferentiated MSCs is that serum is typically used in culture
      protocols to promote differentiation of the osteogenic component, whereas
      existing chondrogenic differentiation protocols rely on the use of serum-free
      conditions. In order to define conditions which could be compatible with both
      chondrogenic and osteogenic differentiation in a single bioreactor, we have
      analysed the efficiency of new biphasic differentiation regimes based on
      transient serum exposure followed by serum-free treatment. MSC differentiation
      was assessed either in serum-free medium or with a range of transient exposure to
      serum, and compared to continuous serum-containing treatment. Although osteogenic
      differentation was not supported in the complete absence of serum, marker
      expression and extensive mineralization analyses established that 5 days of
      transient exposure triggered a level of differentiation comparable to that
      observed when serum was present throughout. This initial phase of serum exposure
      was further shown to support the successful chondrogenic differentiation of MSCs,
      comparable to controls maintained in serum-free conditions throughout. This study
      indicates that a culture based on temporal serum exposure followed by serum-free
      treatment is compatible with both osteogenic and chondrogenic differentiation of
      MSCs. These results will allow the development of novel strategies for
      osteochondral tissue engineering approaches using MSCs for regenerative medicine.

PMID- 23161725
TI  - Ring expansion and rearrangements of rhodium(II) azavinyl carbenes.
AB  - Room for expansion: an efficient, regioselective, and convergent method for the
      ring expansion and rearrangement of 1-sulfonyl-1,2,3-triazoles under rhodium(II)
      catalyzed conditions is described. These denitrogenative reactions form
      substituted enaminone and olefin-based products. The enaminone products can be
      further functionalized to give various heterocycles and ketone derivatives, thus
      rendering the sulfonyl triazole traceless.

PMID- 23161726
TI  - Different strategies for the preconcentration and separation of parabens by
      capillary electrophoresis.
AB  - Several strategies, namely, large volume sample stacking (LVSS), field-amplified
      sample injection (FASI), sweeping, and in-line SPE-CE, were investigated for the
      simultaneous separation and preconcentration of a group of parabens. A BGE
      consisting of 20 mM sodium dihydrogenphosphate (pH 2.28) and 150 mM SDS with 15%
      ACN was used for the separation and preconcentration of the compounds by
      sweeping, and a BGE consisting of 30 mM sodium borate (pH 9.5) was used for the
      separation and preconcentration of the compounds by LVSS, FASI, and in-line SPE
      CE. Several factors affecting the preconcentration process were investigated in
      order to obtain the maximum enhancement of sensitivity. The LODs obtained for
      parabens were in the range of 18-27, 3-4, 2, and 0.01-0.02 ng/mL, and the
      sensitivity evaluated in terms of LODs was improved up to 29-, 77-, 120-, and
      18,400-fold for sweeping, LVSS, FASI, and in-line SPE-CE, respectively. These
      preconcentration techniques showed potential as good strategies for focusing
      parabens. The four methods were validated with standard samples to show the
      potential of these techniques for future applications in real samples, such as
      biological and environmental samples.

PMID- 23161727
TI  - Solvated protein-protein docking using Kyte-Doolittle-based water preferences.
AB  - HADDOCK is one of the few docking programs that can explicitly account for water
      molecules in the docking process. Its solvated docking protocol starts from
      hydrated molecules and a fraction of the resulting interfacial waters is
      subsequently removed in a biased Monte Carlo procedure based on water-mediated
      contact probabilities. The latter were derived from an analysis of water contact
      frequencies from high-resolution crystal structures. Here, we introduce a simple
      water-mediated amino acid-amino acid contact probability scale derived from the
      Kyte-Doolittle hydrophobicity scale and assess its performance on the largest
      high-resolution dataset developed to date for solvated docking. Both scales yield
      high-quality docking results. The novel and simple hydrophobicity scale, which
      should reflect better the physicochemical principles underlying contact
      propensities, leads to a performance improvement of around 10% in ranking,
      cluster quality and water recovery at the interface compared with the statistics
      based original solvated docking protocol.

PMID- 23161729
TI  - Experimental verification of an equivalent circuit for the characterization of
      electrothermal micropumps: high pumping velocities induced by the external
      inductance at driving voltages below 5 V.
AB  - Electrothermal micropumps (ETMUPs) use local heating to create conductivity and
      permittivity gradients in the pump medium. In the presence of such gradients, an
      external AC electric field influences smeared spatial charges in the bulk of the
      medium. When there is also a symmetry break, the field-charge interaction results
      in an effective volumetric force resulting in medium pumping. The advantages of
      the ETMUP principle are the absence of moving parts, the opportunity to passivate
      all the pump structures, homogeneous pump-channel cross-sections, as well as
      force plateaus in broad frequency ranges. The ETMUPs consisted of a DC-heating
      element and AC field electrodes arranged in a 1000 MUm * 250 MUm * 60 MUm (length
      * width * height) channel. They were processed as platinum structures on glass
      carriers. An equivalent-circuit diagram allowed us to model the frequency
      dependent pumping velocities of passivated and nonpassivated ETMUPs, which were
      measured at medium conductivities up to 1.0 S/m in the 300 kHz to 52 MHz
      frequency range. The temperature distributions within the pumps were controlled
      by thermochromic beads. Under resonance conditions, an additional inductance
      induced a tenfold pump-velocity increase to more than 50 MUm/s at driving
      voltages of 5 V(rms). A further miniaturization of the pumps is viewed as quite
      feasible.

PMID- 23161728
TI  - Complex small-molecule architectures regulate phenotypic plasticity in a
      nematode.
AB  - Chemistry the worm's way: The nematode Pristionchus pacificus constructs
      elaborate small molecules from modified building blocks of primary metabolism,
      including an unusual xylopyranose-based nucleoside (see scheme). These compounds
      act as signaling molecules to control adult phenotypic plasticity and dauer
      development and provide examples of modular generation of structural diversity in
      metazoans.

PMID- 23161730
TI  - Site-specific identification of an abeta fibril-heparin interaction site by using
      solid-state NMR spectroscopy.
AB  - At the surface of Abeta(1-40) amyloid fibrils that have a threefold molecular
      symmetry (green in the left picture) a site of interaction of the
      glycosaminoglycan analogue heparin (blue) was identified. The binding site
      consists of residues at the N terminus and the turn regions defining the apices
      of the triangular geometry. Heparin has a lower affinity for Abeta(1-40) fibrils
      having twofold molecular symmetry, thus revealing a remarkable morphological
      selectivity.

PMID- 23161732
TI  - Optimizing diffusive transport through a synthetic membrane channel.

PMID- 23161731
TI  - Laminar silk scaffolds for aligned tissue fabrication.
AB  - 3D-biomaterial scaffolds with aligned architecture are of vital importance in
      tissue regeneration. A generic method is demonstrated to produce aligned
      biomaterial scaffolds using the physics of directional ice freezing.
      Homogeneously aligned 3D silk scaffolds with high porosity and alignment are
      prepared. The method can be adapted to a wide range of polymers and is devoid of
      any chemical reactions, thus avoiding potential complications associated with by
      products. Mechanical properties and cellular responses with chondrocytes and bone
      marrow-derived hMSCs are studied, assessing survival, proliferation, and
      differentiation. In vivo tests suggest biocompatibility of the matrices for
      future tissue engineering applications, specifically in areas where high cellular
      alignment is needed.

PMID- 23161736
TI  - Effects of inbreeding on mouthpart deformities of Chironomus riparius under
      sublethal pesticide exposure.
AB  - Mouthpart deformities in chironomids have been reported to indicate adverse
      effects of environmental pollutants. The authors assessed rates of mouthpart
      deformities in tributyltin-exposed, inbred, and outcrossed Chironomus riparius
      larvae over multiple generations. The authors found that the occurrence of
      mouthpart deformities was significantly correlated with inbreeding, whereas no
      correlation was found with the tributyltin exposure. The present study confirms
      the strong effect of high inbreeding rates on developmental deformities in
      chironomids.

PMID- 23161735
TI  - Microglia response and in vivo therapeutic potential of methylprednisolone-loaded
      dendrimer nanoparticles in spinal cord injury.
AB  - The control and manipulation of cells that trigger secondary mechanisms following
      spinal cord injury (SCI) is one of the first opportunities to minimize its highly
      detrimental outcomes. Herein, the ability of surface-engineered
      carboxymethylchitosan/polyamidoamine (CMCht/PAMAM) dendrimer nanoparticles to
      intracellularly deliver methylprednisolone (MP) to glial cells, allowing a
      controlled and sustained release of this corticosteroid in the injury site, is
      investigated. The negatively charged MP-loaded CMCht/PAMAM dendrimer
      nanoparticles with sizes of 109 nm enable a MP sustained release, which is
      detected for a period of 14 days by HPLC. In vitro studies in glial primary
      cultures show that incubation with 200 MUg mL(-1) nanoparticles do not affect the
      cells' viability or proliferation, while allowing the entire population to
      internalize the nanoparticles. At higher concentrations, microglial cell
      viability is proven to be affected in response to the MP amount released.
      Following lateral hemisection lesions in rats, nanoparticle uptake by the spinal
      tissue is observed 3 h after administration. Moreover, significant differences in
      the locomotor output between the controls and the MP-loaded nanoparticle-treated
      animals one month after the lesion are observed. Therefore, MP-loaded CMCht/PAMAM
      dendrimer nanoparticles may prove to be useful in the reduction of the secondary
      injury following SCI.

PMID- 23161737
TI  - Detection of silver nanoparticles on a lab-on-chip platform.
AB  - The prevalent use of silver nanoparticles (AgNPs) in commercial goods has brought
      forth an urgent need for environmental salvation. With the global river systems
      being contaminated by AgNPs, fast and efficient detection systems are needed to
      trace the presence of AgNPs in common water to prevent detrimental effects to the
      public health. In this work, the detection of AgNPs via electrochemical oxidation
      has been achieved on a "Lab-on-chip" platform. This platform provides a fast,
      convenient, and portable detection system for the detection of AgNPs in common
      water. 

PMID- 23161738
TI  - Metacarpophalangeal joint orientation in anthropoid manual phalanges.
AB  - The proximal articular surface angle of orientation (AO) of proximal phalanges of
      the hand and foot has been used to infer the locomotor profile of extinct Miocene
      catarrhines and early hominins. Previous work has found that joint orientation
      distinguishes quadrupedal from suspensory anthropoids. The purpose of this study
      is to expand on previous research by examining this feature within and across
      several primate clades, allowing us to investigate the potential influences of
      locomotion, substrate usage, hand posture, and phylogeny. We also report AO
      measurements in human proximal hand phalanges, allowing us to examine human
      skeletal variation within a wide comparative context. The angle of orientation
      was measured on manual proximal third phalanges of 21 extant anthropoid species
      using a Microscribe digitizer. Comparisons were made between locomotor groups
      within hominoids, platyrrhines, and cercopithecoids. Proximal phalanges of
      quadrupedal species were characterized by greater dorsal orientation than those
      of suspensory taxa in hominoids and atelids. In addition, arboreal quadrupeds had
      greater AO values than terrestrial quadrupeds within the Cercopithecoidea.
      However, within the terrestrial locomotor group, mean AO values did not differ
      between palmigrade and digitigrade taxa. Thus, while there appears to be a
      functional signal related to substrate usage, differences in use of hand postures
      when moving on the ground were not reflected in proximal joint orientation of the
      proximal phalanx. Finally, we measured relatively low AO values in human
      phalanges, which might be related to integration with serially homologous pedal
      phalanges that are under strong selective pressure related to bipedalism.

PMID- 23161740
TI  - Total synthesis of the unusual monoterpenoid indole alkaloid (+/-)-alstilobanine
      A.

PMID- 23161741
TI  - Putative cholesterol-binding sites in human immunodeficiency virus (HIV)
      coreceptors CXCR4 and CCR5.
AB  - Using molecular docking, we identified a cholesterol-binding site in the groove
      between transmembrane helices 1 and 7 near the inner membrane-water interface of
      the G protein-coupled receptor CXCR4, a coreceptor for HIV entry into cells. In
      this docking pose, the amino group of lysine K67 establishes a hydrogen bond with
      the hydroxyl group of cholesterol, whereas tyrosine Y302 stacks with cholesterol
      by its aromatic side chain, and a number of residues form hydrophobic contacts
      with cholesterol. Sequence alignment showed that a similar putative cholesterol
      binding site is also present in CCR5, another HIV coreceptor. We suggest that the
      interaction of cholesterol with these putative cholesterol-binding sites in CXCR4
      and CCR5 is responsible for the presence of these receptors in lipid rafts, for
      the effect of cholesterol on their conformational stability and function, and for
      the role that cell cholesterol plays in the cell entry of HIV strains that use
      these membrane proteins as coreceptors. We propose that mutations of residues
      that are involved in cholesterol binding will make CXCR4 and CCR5 insensitive to
      membrane cholesterol content. Cholesterol-binding sites in HIV coreceptors are
      potential targets for steroid drugs that bind to CXCR4 and CCR5 with higher
      binding affinity than cholesterol, but do not stabilize the native conformation
      of these proteins.

PMID- 23161742
TI  - Facile route to an all-organic, triply threaded, interlocked structure by
      templated dynamic clipping.
AB  - Encaged! Three-terminal interlocked molecular species were obtained by dynamic
      (2+3) assembly of a cagelike macro-bicycle around a trifurcated trispyridinium pi
      guest. The complex is stabilized by pi-pi interactions and multiple [C-H???O] and
      [C-H???N] interactions. Uncomplexed guest molecules cocrystallize alongside the
      threaded complexes in the solid state, thus giving extended pi-stacked columns.

PMID- 23161743
TI  - Quantitative structure-mobility relationship analysis of imidazoline receptor
      ligands in CDs-mediated CE.
AB  - The performed quantitative structure-mobility relationship (QSMR) study has
      investigated relative migration times of 11 guanidine/imidazoline derivatives,
      imidazoline receptor ligands, in CE system containing one of CDs, alpha-, beta-,
      or gamma-CD, using linear and nonlinear modeling methods. The analyzed ligands
      and their inclusion complexes with CDs were fully examined and optimized at
      semiempirical parametrized model 3 level. The density functional theory, such as
      B3LYP/6-31G+(d,p)/3-21G(d)/STO-3G(d,p)/STO-3G(d), and ab initio theory, such as
      HF/3-21G(d)/STO-3G(d), were applied for molecular descriptors computation of the
      optimized ligands and their complexes. Predictive performances of the developed
      QSMR models were tested by use of the cross-validation and external test set
      prediction. Obtained results for Q(2)  values (0.869, 0.911, and 0.966 for CE
      system containing alpha-, beta-, and gamma-CD, respectively) and root mean
      squared error of prediction (0.239, 0.242, and 0.288 for alpha-, beta-, and gamma
      CD, respectively) were proved high predictive power of the proposed models.
      Finally, multitarget QSMR model, using the ligands descriptors (X) and the
      relative migration time in presence of alpha-CD (Y1), beta-CD (Y2), and gamma-CD
      (Y3), has been created. The multitarget QSMR model can be used as initial
      screening predictive tool for CE migration behavior of other related
      guanidine/imidazoline derivatives in presence of alpha-, beta-, and gamma-CD.

PMID- 23161744
TI  - Tellurium thin films in hybrid organic electronics: morphology and mobility.
AB  - Elemental Te displays a wide variety of nanoscale morphologies of vapor-deposited
      films, depending on the substrate surface and temperature. These morphologies are
      correlated to field-effect mobilities in transistors made with Te as the lone
      semiconductor or from Te-organic multilayer semiconductors. Two examples of
      morphologies and transistor output characteristics, i.e., on a room temperature
      oxide and heated organic, are shown in the figure.

PMID- 23161745
TI  - Biocompatible multishell architecture for iron oxide nanoparticles.
AB  - The coating of super-paramagnetic iron oxide nanoparticles (SPIONs) with multiple
      shells is demonstrated by building a layer assembled from carboxymethyldextran
      and poly(diallydimethylammonium chloride). Three shells are produced stepwise
      around aggregates of SPIONs by the formation of a polyelectrolyte complex. A
      growing particle size from 96 to 327 nm and a zeta potential in the range of +39
      to -51 mV are measured. Microscopic techniques such as TEM, SEM, and AFM
      exemplify the core-shell structures. Magnetic force microscopy and vibrating
      sample magnetometer measurements confirm the architecture of the multishell
      particles. Cell culture experiments show that even nanoparticles with three
      shells are still taken up by cells.

PMID- 23161746
TI  - In vitro expressed GPCR inserted in polymersome membranes for ligand-binding
      studies.
AB  - The dopamine receptor D2 (DRD2), a G-protein coupled receptor is expressed into
      PBd(22)-PEO(13) and PMOXA(20)-PDMS(54)-PMOXA(20) block copolymer vesicles. The
      conformational integrity of the receptor is confirmed by antibody- and ligand
      binding assays. Replacement of bound dopamine is demonstrated on surface
      immobilized polymersomes, thus making this a promising platform for drug
      screening.

PMID- 23161747
TI  - Large area resist-free soft lithographic patterning of graphene.
AB  - Large area low-cost patterning is a challenging problem in graphene research. A
      resist-free, single-step, large area and cost effective soft lithographic
      patterning strategy is presented for graphene. The technique is applicable on any
      arbitrary substrate that needs to be covered with a graphene film and provides a
      viable route to large-area patterning of graphene for device applications.

PMID- 23161748
TI  - Replicative mechanisms of CNV formation preferentially occur as intrachromosomal
      events: evidence from Potocki-Lupski duplication syndrome.
AB  - Copy number variations (CNVs) in the human genome contribute significantly to
      disease. De novo CNV mutations arise via genomic rearrangements, which can occur
      in 'trans', i.e. via interchromosomal events, or in 'cis', i.e. via
      intrachromosomal events. However, what molecular mechanisms occur between
      chromosomes versus between or within chromatids has not been systematically
      investigated. We hypothesized that distinct CNV mutational mechanisms, based on
      their intrinsic properties, may occur in a biased intrachromosomal versus
      interchromosomal manner. Here, we studied 62 genomic duplications observed in
      association with sporadic Potocki-Lupski syndrome (PTLS), in which multiple
      mutational mechanisms appear to be operative. Intriguingly, more interchromosomal
      than intrachromosomal events were identified in recurrent PTLS duplications
      mediated by non-allelic homologous recombination, whereas the reciprocal
      distribution was found for replicative mechanisms and non-homologous end-joining,
      likely reflecting the differences in spacial proximity of homologous chromosomes
      during different mutational processes.

PMID- 23161750
TI  - Osteogenesis and expression of the bone marrow niche in endothelial cell-depleted
      HipOPs.
AB  - The identification and purification of murine multipotent mesenchymal stem cells
      (MSCs) have been difficult due to their low frequency, the presence of
      contaminating cell types and lack of unambiguous markers. Using a magnetic micro
      beads negative selection technique to remove hematopoietic cells from mouse bone
      marrow stromal cells (BMSCs), our lab recently isolated a highly purified
      osteoprogenitor (HipOP) population that was also enriched for other mesenchymal
      precursors, including MSCs [Itoh and Aubin, 2009]. We now report that HipOPs are
      also highly enriched in vascular endothelial cells (VECs), which we hypothesized
      were an accessory cell type regulating osteogenesis. However, when VECs were
      immunodepleted from HipOPs with anti-CD31 antibodies, the resulting CD31(-) HipOP
      population had equal osteogenic capacity to the HipOPs in vitro and in vivo.
      Analysis of gene expression of Ncad, Pth1r, Ang1, Cxcl12, Jag1, Pdgfr-beta, alpha
      sma, Desmin, and Ng2 suggested that both HipOPs and CD31(-) HipOPs are
      hemopoietic stem cell (HSC) niche populations. However, the data support the view
      that osteoblast differentiation and depletion of VECs modulate the HSC niche.

PMID- 23161749
TI  - Haploinsufficiency at the human IFNGR2 locus contributes to mycobacterial
      disease.
AB  - Mendelian susceptibility to mycobacterial diseases (MSMD) is a rare syndrome, the
      known genetic etiologies of which impair the production of, or the response to
      interferon-gamma (IFN-gamma). We report here a patient (P1) with MSMD whose cells
      display mildly impaired responses to IFN-gamma, at levels, however, similar to
      those from MSMD patients with autosomal recessive (AR) partial IFN-gammaR2 or
      STAT1 deficiency. Whole-exome sequencing (WES) and Sanger sequencing revealed
      only one candidate variation for both MSMD-causing and IFN-gamma-related genes.
      P1 carried a heterozygous frame-shift IFNGR2 mutation inherited from her father.
      We show that the mutant allele is intrinsically loss-of-function and not dominant
      negative, suggesting haploinsufficiency at the IFNGR2 locus. We also show that
      Epstein-Barr virus transformed B lymphocyte cells from 10 heterozygous relatives
      of patients with AR complete IFN-gammaR2 deficiency respond poorly to IFN-gamma,
      in some cases as poorly as the cells of P1. Naive CD4(+) T cells and memory IL-4
      producing T cells from these individuals also responded poorly to IFN-gamma,
      whereas monocytes and monocyte-derived macrophages (MDMs) did not. This is
      consistent with the lower levels of expression of IFN-gammaR2 in lymphoid than in
      myeloid cells. Overall, MSMD in this patient is probably due to autosomal
      dominant (AD) IFN-gammaR2 deficiency, resulting from haploinsufficiency, at least
      in lymphoid cells. The clinical penetrance of AD IFN-gammaR2 deficiency is
      incomplete, possibly due, at least partly, to the variability of cellular
      responses to IFN-gamma in these individuals.

PMID- 23161751
TI  - Do subtoxic levels of chlorate influence the desiccation tolerance of Egeria
      densa?
AB  - Among the different factors hypothesized to be responsible for the virtual
      disappearance of Egeria densa, once a dominant aquatic macrophyte in a southern
      Chile wetland ecosystem, are the negative effects of certain chemical compounds
      (mainly chlorate) and harsh environmental conditions (desiccation caused by
      prolonged atmospheric exposure). The authors performed an integrated experiment
      in which E. densa plants were first exposed for four weeks inside a mesocosm
      system to levels of chlorate that existed in the wetland at the time of the
      plant's demise and then exposed to desiccation conditions that also resembled
      those that the system had experienced. Hence, the authors tested the hypothesis
      that E. densa plants exposed to sublethal levels of chlorate are more susceptible
      to the deleterious effect of desiccation compared with plants that had not been
      exposed to chlorate. This hypothesis was tested by means of quantifying
      physiologically related parameters in plants right after the four weeks under
      water and then after the desiccation period of 6 h. Their results rejected this
      hypothesis, because all plants, regardless of their history, are equally affected
      by desiccation.

PMID- 23161752
TI  - The prognostic value of the metastatic lymph node ratio and maximal metastatic
      tumor size in pathological N1a papillary thyroid carcinoma.
AB  - OBJECTIVE: The presence of central neck lymph node (LN) metastases (defined as
      pN1a according to Tumor Node Metastasis classification) in papillary thyroid
      cancer (PTC) is known as an independent risk factor for recurrence. Extent of LN
      metastasis and the completeness of removal of metastatic LN must have an impact
      on prognosis but they are not easy to measure. Moreover, the significance of the
      size of metastatic tumors in LNs has not been clarified. This study was to
      evaluate the impact of the extent of LN metastasis and size of metastatic tumors
      on the recurrence in pathological N1a PTC. DESIGN: This retrospective
      observational cohort study enrolled 292 PTC patients who underwent total
      thyroidectomy with central neck dissection from 1999 to 2005. LN ratio was
      defined as the number of metastatic LNs divided by the number of removed LNs,
      which was regarded as variable reflecting both extent of LN metastasis and
      completeness of resection, and LN size as the maximal diameter of tumor in
      metastatic LN. RESULTS: The significant risk factors for recurrence in univariate
      analysis were large primary tumor size (defined as larger than 2 cm), high LN
      ratio (defined as higher than 0.4), and presence of macrometastasis (defined as
      larger than 0.2 cm). Age, sex, clinical node status, and microscopic
      perithyroidal extension had no effect on recurrence. In multivariate analysis,
      high LN ratio and presence of macrometastasis were independent risk factors for
      recurrence. CONCLUSION: LN ratio and size of metastatic nodes had a significant
      prognostic value in pathological N1a PTC. We suggest that risk stratification of
      pathological N1a PTC according to the pattern of LN metastasis such as LN ratio
      and size would give valuable information to clinicians.

PMID- 23161753
TI  - A cohort effect on serum testosterone levels in Finnish men.
AB  - OBJECTIVE: To investigate whether a population-level decline in serum
      testosterone exists in Finnish men. In comparison with other European
      populations, Finnish men have compared well in the studies of reproductive health
      (i.e. semen quality, incidence of cryptorchidism and testicular cancer); thus, we
      expected no significant cohort-dependent decrease in serum testosterone. METHODS:
      We analysed serum levels of testosterone, gonadotrophin and sex hormone binding
      globulin (SHBG) in 3271 men representing different ages (25-74 years) and birth
      cohorts within three large Finnish population surveys conducted in 1972, 1977 and
      2002. RESULTS: Serum testosterone levels decreased (from 25.3 nmol/l in 25- to 29
      year-old men gradually to 16.9 nmol/l in 70- to 74-year-old men), whereas SHBG
      and gonadotrophin levels increased with increasing age. In addition, a
      significant secular trend in testosterone (total and free), SHBG and
      gonadotrophin levels was observed with lower levels in more recently born age
      matched men. Serum testosterone level decreased in men aged 60-69 years from 21.9
      nmol/l (men born 1913-1922) to 13.8 nmol/l (men born 1942-1951). These decreases
      remained significant following adjustment for BMI. An age-independent birth
      cohort effect existed on reproductive hormones measured in the Finnish men. In
      concert with the lower free testosterone levels, we observed lower gonadotrophin
      levels, suggesting that while there may be detrimental changes at the gonad
      level, the hypothalamus-pituitary-axis is not responding appropriately to this
      change. CONCLUSIONS: The more recently born Finnish men have lower testosterone
      levels than their earlier born peers. This study offers no explanation for this
      substantial recent adverse development.

PMID- 23161754
TI  - Morphological and immunohistochemical features of the vomeronasal system in dogs.
AB  - Each of the structures integrating the sense of smell in mammals has a different
      degree of development, even in the so-called macrosmatic animals, according to
      the capacity of the olfactory system to detect thousands of different chemical
      signals. Such morphological diversity implies analogous physiological variation.
      The study of the accessory olfactory system, also known as the vomeronasal
      system, is a useful way to analyze the heterogeneity of the sense of smell.
      Macrodissection and microdissection methods as well as conventional histology and
      immunohistochemistry protocols were used to study aspects of the vomeronasal
      organ and the accessory olfactory bulbs in dogs. Observations regarding the end
      of the anterior part of the vomeronasal duct have been emphasized. Both lectins,
      Ulex europaeus agglutinin I and Lycopersicum esculentum agglutinin, and one G
      protein, G(alphai2), show a similar pattern of binding in the sensory epithelium
      of the vomeronasal organ and in the vomeronasal nerve and glomerular layers of
      the accessory olfactory bulb, whereas the expression of protein G(alphao) was not
      observed. Taken together, our results emphasize the contribution of comparative
      data to our understanding of the vomeronasal system function.

PMID- 23161757
TI  - Palladium-catalyzed synthesis and isolation of functionalized allylboronic acids:
      selective, direct allylboration of ketones.
AB  - Textbook revision: allylboronic acids, which are easily prepared from allylic
      alcohols, react readily and selectively with ketones without Lewis acid
      catalysts.

PMID- 23161756
TI  - A broad specificity nucleoside kinase from Thermoplasma acidophilum.
AB  - The crystal structure of Ta0880, determined at 1.91 A resolution, from
      Thermoplasma acidophilum revealed a dimer with each monomer composed of an
      alpha/beta/alpha sandwich domain and a smaller lid domain. The overall fold
      belongs to the PfkB family of carbohydrate kinases (a family member of the
      Ribokinase clan) which include ribokinases, 1-phosphofructokinases, 6
      phosphofructo-2-kinase, inosine/guanosine kinases, fructokinases, adenosine
      kinases, and many more. Based on its general fold, Ta0880 had been annotated as a
      ribokinase-like protein. Using a coupled pyruvate kinase/lactate dehydrogenase
      assay, the activity of Ta0880 was assessed against a variety of ribokinase/pfkB
      like family substrates; activity was not observed for ribose, fructose-1
      phosphate, or fructose-6-phosphate. Based on structural similarity with
      nucleoside kinases (NK) from Methanocaldococcus jannaschii (MjNK, PDB 2C49, and
      2C4E) and Burkholderia thailandensis (BtNK, PDB 3B1O), nucleoside kinase activity
      was investigated. Ta0880 (TaNK) was confirmed to have nucleoside kinase activity
      with an apparent KM for guanosine of 0.21 MUM and catalytic efficiency of 345,000
      M(-1) s(-1) . These three NKs have significantly different substrate, phosphate
      donor, and cation specificities and comparisons of specificity and structure
      identified residues likely responsible for the nucleoside substrate selectivity.
      Phylogenetic analysis identified three clusters within the PfkB family and
      indicates that TaNK is a member of a new sub-family with broad nucleoside
      specificities. Proteins 2013. (c) 2012 Wiley Periodicals, Inc.

PMID- 23161758
TI  - Similar but different: thermodynamic and structural characterization of a pair of
      enantiomers binding to acetylcholinesterase.

PMID- 23161755
TI  - Alterations in replication timing of cancer-related genes in malignant human
      breast cancer cells.
AB  - The replication timing of nine genes commonly involved in cancer was investigated
      in the MCF10 cell lines for human breast cancer progression. Six of these nine
      genes are part of a constellation of tumor suppressor genes that play a major
      role in familial human breast cancer (TP53, ATM, PTEN, CHK2, BRCA1, and BRCA2).
      Three other genes are involved in a large number of human cancers including
      breast as either tumor suppressors (RB1 and RAD51) or as an oncogene (cMYC). Five
      of these nine genes (TP53, RAD51, ATM, PTEN, and cMYC) show significant
      differences (P < 0.05) in replication timing between MCF10A normal human breast
      cells and the corresponding malignant MCF10CA1a cells. These differences are
      specific to the malignant state of the MCF10CA1a cells since there were no
      significant differences in the replication timing of these genes between normal
      MCF10A cells and the non-malignant cancer MCF10AT1 cells. Microarray analysis
      further demonstrated that three of these five genes (TP53, RAD51, and cMYC)
      showed significant changes in gene expression (>=2-fold) between normal and
      malignant cells. Our findings demonstrate an alteration in the replication timing
      of a small subset of cancer-related genes in malignant breast cancer cells. These
      alterations partially correlate with the major transcriptional changes
      characteristic of the malignant state in these cells.

PMID- 23161759
TI  - Surfactant-free scalable synthesis of Bi2 Te3 and Bi2Se3 nanoflakes and enhanced
      thermoelectric properties of their nanocomposites.
AB  - Surfactant-free nanoflakes of n-type Bi2 Te3 and Bi2 Se3 are synthesized in high
      yields. Their suspensions are mixed to create nanocomposites with
      heterostructured nanograins. A maximum ZT (0.7 at 400 K) is achieved with a broad
      content of 10-15% Bi2 Se3 in the nanocomposites.

PMID- 23161760
TI  - A versatile toolbox for multiplexed protein micropatterning by laser lithography.
AB  - Photocleavable oligohistidine peptides (POHP) allow in situ spatial organization
      of multiple His-tagged proteins onto surfaces functionalized with
      tris(nitrilotriacetic acid) (tris-NTA). Here, a second generation of POHPs is
      presented with improved photoresponse and site-specific covalent coupling is
      introduced for generating stable protein assemblies. POHPs with different numbers
      of histidine residues and a photocleavable linker based on the 4,5-dimethoxy-o
      nitrophenyl ethyl chromophore are prepared. These peptides show better
      photosensitivity than the previously used o-nitrophenyl ethyl derivative.
      Efficient and stable caging of tris-NTA-functionalized surfaces by POHPs
      comprising 12 histidine residues is demonstrated by multiparameter solid-phase
      detection techniques. Laser lithographic uncaging by photofragmentation of the
      POHPs is possible with substantially reduced photodamage as compared to previous
      approaches. Thus, in situ micropatterning of His-tagged proteins under
      physiological conditions is demonstrated for the first time. In combination with
      a short peptide tag for a site-specific enzymatic coupling reaction, covalent
      immobilization of multiple proteins into target micropatterns is possible under
      physiological conditions.

PMID- 23161761
TI  - A survey of husbandry practices for lorisid primates in North American zoos and
      related facilities.
AB  - Zoos and related facilities in North America currently manage five species in the
      primate family Lorisidae: the greater (Nycticebus coucang), Bengal (N.
      bengalensis) and pygmy (N. pygmaeus) slow lorises, red slender loris (Loris
      tardigradus), and potto (Perodicticus potto). We used an online survey to
      describe institutional housing and husbandry practices for these species and
      assess the extent to which practices are consistent with established guidelines.
      Our results show that most captive lorisids are housed solitarily or in pairs.
      Most individuals occupy a single exhibit space in a building dedicated to
      nocturnal animals. Facilities are commonly meeting recommendations for abiotic
      exhibit design and are providing animals with an enriched environment. However,
      pottos and slender lorises currently occupy exhibit spaces smaller than the
      recommended minimum, and the impact of cleaning protocols on olfactory
      communication should be critically evaluated. Few facilities are taking advantage
      of the benefits of positive reinforcement training for promoting animal welfare.
      Research is greatly needed on the effects of exhibit lighting on behavior,
      health, and reproduction; and to determine how best to manage the social needs of
      lorisids with naturally dispersed social structures. Although captive populations
      of slender lorises, pottos, and slow lorises are declining, we suggest that
      improved husbandry knowledge has the potential to positively influence population
      sustainability and to enhance future efforts to manage the growing pygmy loris
      population.

PMID- 23161762
TI  - A homonuclear rotational echo double-resonance method for measuring site-resolved
      distance distributions in I=1/2 spin pairs, clusters, and multispin systems.

PMID- 23161763
TI  - In vitro 3D full-thickness skin-equivalent tissue model using silk and collagen
      biomaterials.
AB  - Current approaches to skin equivalents often only include the epidermis and
      dermis. Here, a full-thickness skin equivalent is described including epidermis,
      dermis, and hypodermis, that could serve as an in vitro model for studying skin
      biology or as a platform for consumer product testing. The construct is easy to
      handle and is maintained for >14 d while expressing physiological morphologies of
      the epidermis and dermis, seen by keratin 10, collagens I and IV expression. The
      skin equivalent produces glycerol and leptin, markers of adipose metabolism. This
      work serves as a foundation for understanding a few necessary factors needed to
      develop a stable, functional model of full-thickness skin.

PMID- 23161764
TI  - Oral treatment of chickens with Lactobacillus reuteri LM1 reduces Brachyspira
      pilosicoli-induced pathology.
AB  - Avian intestinal spirochaetosis (AIS) results from the colonization of the caeca
      and colon of poultry by pathogenic Brachyspira, notably Brachyspira pilosicoli.
      Following the ban on the use of antibiotic growth promoters in the European Union
      in 2006, the number of cases of AIS has increased, which, alongside emerging
      antimicrobial resistance in Brachyspira, has driven renewed interest in
      alternative intervention strategies. Lactobacillus-based probiotics have been
      shown to protect against infection with common enteric pathogens in livestock.
      Our previous studies have shown that Lactobacillus reuteri LM1 antagonizes
      aspects of the pathobiology of Brachyspira in vitro. Here, we showed that L.
      reuteri LM1 mitigates the clinical symptoms of AIS in chickens experimentally
      challenged with B. pilosicoli. Two groups of 15 commercial laying hens were
      challenged experimentally by oral gavage with B. pilosicoli B2904 at 18 weeks of
      age; one group received unsupplemented drinking water and the other received L.
      reuteri LM1 in drinking water from 1 week prior to challenge with Brachyspira and
      thereafter for the duration of the study. This treatment regime was protective.
      Specifically, B. pilosicoli was detected by culture in fewer birds, bird weights
      were higher, faecal moisture contents were significantly lower (P<0.05) and egg
      production as assessed by egg weight and faecal staining score was improved
      (P<0.05). Also, at post-mortem examination, significantly fewer B. pilosicoli
      were recovered from treated birds (P<0.05), with only mild-moderate
      histopathological changes observed. These data suggest that L. reuteri LM1 may be
      a useful tool in the control of AIS.

PMID- 23161765
TI  - Molecular characterization of carbapenemase-producing clinical isolates of
      Enterobacteriaceae in a teaching hospital, Japan.
AB  - We examined the molecular characteristics of 13 phenotypically confirmed
      carbapenemase-positive Enterobacteriaceae clinical isolates, including the
      relationships between plasmid-mediated quinolone-resistance genes (qnr), 6'-N
      aminoglycoside acetyltransferase-encoding genes [aac(6')] and AmpC-encoding genes
      (pAmpC). Twelve isolates were bla(IMP-1) positive (92.3%), while one was bla(IMP
      11) positive (7.7%). We detected qnr, aac(6') and pAmpC genes designated bla(ACT
      1)-like in 76.9%, 100% and 53.8%, respectively, of the 13 isolates. Plasmids were
      transferred successfully for three of the 13 metallo-beta-lactamase (MBL)
      producing isolates, and the sizes of plasmids extracted from these donors and
      transconjugants were deduced to be 65 kb or 70 kb. OmpC or OmpF protein
      expression was reduced in all Enterobacter cloacae, and one Klebsiella oxytoca
      lacked OmpK36. We demonstrate what appears to be the first evidence that, in
      Japan, Enterobacteriaceae producing MBLs carry various plasmid-mediated
      resistance genes, which may cause a further decrease in carbapenem susceptibility
      through reduction of the expression of outer-membrane proteins.

PMID- 23161766
TI  - Inhibition of biofilm maturation by linezolid in meticillin-resistant
      Staphylococcus epidermidis clinical isolates: comparison with other drugs.
AB  - Biofilm resistance mechanisms are multifactorial and vary from one organism to
      another. The purpose of this study was to investigate the efficacy of linezolid
      against indwelling device-related meticillin-resistant Staphylococcus epidermidis
      (MRSE) biofilm, and compare this with other antimicrobials. MICs, minimum biofilm
      inhibitory concentrations (MBICs) and minimum biofilm eradication concentrations
      (MBECs) were determined by the microtitre plate method. Fourteen and thirteen
      isolates from patients with indwelling device-related bacteraemia (IDB) and
      indwelling device colonization not associated with bacteraemia, respectively,
      were assessed. High MBIC was associated with a high intensity of biofilm
      formation (gentamicin r=0.796; linezolid r=0.477; rifampicin r=0.634; tigecycline
      r=0.410; and vancomycin r=0.771), but this correlation was not observed with
      MBEC. Linezolid demonstrated better in vitro antimicrobial activity than other
      antimicrobials (MBIC - gentamicin P<0.001, rifampicin P=0.019, vancomycin
      P=0.008; MBEC - gentamicin P<0.001, rifampicin P=0.002, vancomycin P<0.001).
      Biofilm growth inhibition was strongly associated with biofilm formation
      intensity; however, biofilm eradication was not cell number dependent. MRSE
      biofilm eradication would represent a huge advance for IDB, although high
      concentrations of gentamicin, linezolid, rifampicin, tigecycline and vancomycin
      were required for that. In general, linezolid reached better in vitro
      concentrations and was demonstrated to be highly active against MRSE biofilms by
      inhibiting their growth during biofilm formation.

PMID- 23161767
TI  - Extended-spectrum beta-lactamase/AmpC-producing uropathogenic Escherichia coli
      from HIV patients: do they have a low virulence score?
AB  - Extended-spectrum beta-lactamase (ESBL) production and quinolone resistance are
      often associated in enterobacteria. Prior exposure to 3G
      cephalosporins/quinolones accelerates the risk of resistance to both these groups
      of antibiotics. Hence, information on the antimicrobial resistance pattern of
      uropathogenic Escherichia coli (UPEC) isolates is important to better formulate
      the guidelines for the empirical therapy of urinary tract infection in the
      context of HIV/AIDS. The aim of this study was to determine the incidence of
      ESBL/AmpC and fluoroquinolone (FQ) resistance among urinary E. coli isolates and
      to establish the association of extraintestinal virulence and phylogenetic
      distribution with antibiotic resistance and host immunocompromisation.
      Accordingly, 118 urinary Escherichia coli isolates from HIV (n = 76) and non-HIV
      antenatal patients (n = 42) from Chennai, South India, were analysed for the
      presence of five virulence-associated genes (VAGs): pap, sfa/foc, afa/dra, iutA
      and kpsMII. Compared with the susceptible HIV isolates, the majority of the
      ESBL(+)AmpC(+)FQ(R) isolates harboured iutA (66.7%) and pap (40%). The FQ
      resistant HIV isolates were significantly enriched for iutA (67.8%) and kpsMII
      (47.5%) and qualified as UPEC (54.2%), while a majority of the FQ-susceptible
      isolates from the non-HIV patients were found to harbour pap (48.4%), sfa/foc
      (41.9%) and kpsMII (48.4%) and were classified as UPEC (40.5%). We conclude that
      antibiotic-resistant (ESBL(+)AmpC(+)and/or FQ(R)) phylogroup D isolates with
      limited virulence are competent enough to establish infections in HIV patients,
      while among non-HIV patients, an array of virulence factors is essential for E.
      coli to overcome host defences irrespective of antibiotic resistance.

PMID- 23161768
TI  - Effects of efflux-pump inducers and genetic variation of the multidrug
      transporter cmeB in biocide resistance of Campylobacter jejuni and Campylobacter
      coli.
AB  - Multidrug efflux pumps, such as CmeABC and CmeDEF, are involved in the resistance
      of Campylobacter to a broad spectrum of antimicrobials. The aim of this study was
      to analyse the effects of two putative efflux-pump inducers, bile salts and
      sodium deoxycholate, on the resistance of Campylobacter to biocides (triclosan,
      benzalkonium chloride, chlorhexidine diacetate, cetylpyridinium chloride and
      trisodium phosphate), SDS and erythromycin. The involvement of the CmeABC and
      CmeDEF efflux pumps in this resistance was studied on the basis of the effects of
      bile salts and sodium deoxycholate in Campylobacter cmeB, cmeF and cmeR mutants.
      The genetic variation in the cmeB gene was also examined, to see whether this
      polymorphism is related to the function of the efflux pump. In 15 Campylobacter
      jejuni and 23 Campylobacter coli strains, bile salts and sodium deoxycholate
      increased the MICs of benzalkonium chloride, chlorhexidine diacetate,
      cetylpyridinium chloride and SDS, and decreased the MICs of triclosan, trisodium
      phosphate and erythromycin. Bile salts and sodium deoxycholate further decreased
      or increased the MICs of biocides and erythromycin in the cmeF and cmeR mutants.
      For cmeB polymorphisms, 17 different cmeB-specific PCR-RFLP patterns were
      identified: six within C. jejuni only, nine within C. coli only and two in both
      species. In conclusion, bile salts and sodium deoxycholate can increase or
      decrease bacterial resistance to structurally unrelated antimicrobials. The MIC
      increases in the cmeF and cmeR mutants indicated that at least one non-CmeABC
      efflux system is involved in resistance to biocides. These results indicate that
      the cmeB gene polymorphism identified is not associated with biocide and
      erythromycin resistance in Campylobacter.

PMID- 23161769
TI  - Invasive aspergillosis caused by cryptic Aspergillus species: a report of two
      consecutive episodes in a patient with leukaemia.
AB  - We report a case of two consecutive episodes of invasive aspergillosis caused by
      cryptic Aspergillus species in a patient with leukaemia. A first episode of
      pulmonary infection was caused by Aspergillus calidoustus and Aspergillus
      novofumigatus, and the second episode by A. novofumigatus and Aspergillus
      viridinutans. Fungal isolates were identified to species level using traditional
      and sequencing-based molecular methods.

PMID- 23161770
TI  - Evidence for systemic spread of the potentially zoonotic intestinal spirochaete
      Brachyspira pilosicoli in experimentally challenged laying chickens.
AB  - Brachyspira pilosicoli is a potentially zoonotic anaerobic intestinal spirochaete
      that is one of several species causing avian intestinal spirochaetosis. The aim
      of this study was to develop a reproducible model of infection in point-of-lay
      chickens and compare the virulence of two strains of B. pilosicoli in a model
      using experimentally challenged laying chickens. Seventeen-week-old commercial
      laying chickens were experimentally challenged by oral gavage with either B.
      pilosicoli strain B2904 or CPSp1, following an oral dose of 10 % sodium
      bicarbonate to neutralize acidity in the crop. Approximately 80 % of the chickens
      became colonized and exhibited increased faecal moisture content, reduced weight
      gain and delayed onset of lay. Tissues sampled at post-mortem examination were
      analysed to produce a quantitative output on the number of spirochaetes present
      and hence, the extent of colonization. The liver and spleen were colonized, and
      novel histopathology was observed in these tissues. The infection model we report
      here has potential use in studies to improve our understanding of the mechanisms
      by which Brachyspira elicit disease in poultry and in testing novel intervention
      strategies.

PMID- 23161771
TI  - Presence of the vanC1 gene in a vancomycin-resistant Enterococcus faecalis strain
      isolated from ewe bulk tank milk.

PMID- 23161772
TI  - MT2-MMP expression during early avian morphogenesis.
AB  - Membrane-type 2 matrix metalloproteinase (MT2-MMP; also called MMP15) is a
      membrane-bound protease that degrades extracellular matrix and activates proMMPs
      such as proMMP-2. MMP-2 expression in avian embryos is well documented, but it is
      not clear how proMMP-2 is activated during avian embryogenesis. Herein, we report
      that MT2-MMP mRNA is expressed in several tissues including the neural folds and
      epidermal ectoderm, intermediate mesoderm, pharyngeal arches, limb buds, and
      dermis. Several, but not all, of these tissues are known to express MMP-2. These
      observations suggest MT2-MMP may play a role during embryonic development not
      only through its own proteolytic activity but also by activating proMMP-2.

PMID- 23161773
TI  - Reply to "survival analysis for apparent diffusion coefficient measures in
      children with embryonal brain tumors," by Grech-Sollars et al.

PMID- 23161774
TI  - Survival meta-analyses for >1800 malignant peripheral nerve sheath tumor patients
      with and without neurofibromatosis type 1.
AB  - There are conflicting reports as to whether malignant peripheral nerve sheath
      tumor (MPNST) patients with neurofibromatosis type 1 (NF1) have worse prognosis
      than non-NF1 MPNST patients. Large clinical studies to address this problem are
      lacking due to the rareness of MPNST. We have performed meta-analyses testing the
      effect of NF1 status on MPNST survival based on publications from the last 50
      years, including only nonoverlapping patients reported from each institution. In
      addition, we analyzed survival characteristics for 179 MPNST patients from 3
      European sarcoma centers. The meta-analyses including data from a total of 48
      studies and >1800 patients revealed a significantly higher odds ratio for overall
      survival (OR(OS)) and disease-specific survival (OR(DSS)) in the non-NF1 group
      (OR(OS) = 1.75, 95% confidence interval [CI] = 1.28-2.39, and OR(DSS) = 1.68, 95%
      CI = 1.18-2.40). However, in studies published in the last decade, survival in
      the 2 patient groups has been converging, as especially the NF1 group has shown
      improved prognosis. For our own MPNST patients, NF1 status had no effect on
      overall or disease-specific survival. The compiled literature from 1963 to the
      present indicates a significantly worse outcome of MPNST in patients with NF1
      syndrome compared with non-NF1 patients. However, survival for the NF1 patients
      has improved in the last decade, and the survival difference is diminishing.
      These observations support the hypothesis that MPNSTs arising in NF1 and non-NF1
      patients are not different per se. Consequently, we suggest that the choice of
      treatment for MPNST should be independent of NF1 status.

PMID- 23161776
TI  - Ethylmalonic acid modulates Na+, K(+)-ATPase activity and mRNA levels in rat
      cerebral cortex.
AB  - Ethylmalonic acid (EMA) accumulates in tissues of patients affected by short
      chain acyl-CoA dehydrogenase deficiency and ethylmalonic encephalopathy,
      illnesses characterized by variable neurological symptoms. In this work, we
      investigated the in vitro and in vivo EMA effects on Na(+), K(+)-ATPase (NAK)
      activity and mRNA levels in cerebral cortex from 30-day-old rats. For in vitro
      studies, cerebral cortex homogenates were incubated in the presence of EMA at
      0.5, 1, or 2.5 mM concentrations for 1 h. For in vivo experiments, animals
      received three subcutaneous EMA injections (6 MUmol g(-1); 90-min interval) and
      were killed 60 min after the last injection. After that, NAK activity and its
      mRNA expression were measured. We observed that EMA did not affect this enzyme
      activity in vitro. In contrast, EMA administration significantly increased NAK
      activity and decreased mRNA NAK expression as assessed by semiquantitative
      reverse transcriptase polymerase chain reaction when compared with control group.
      Considering the high score of residues prone to phosphorylation on NAK, this
      profile can be associated with a possible regulation by specific phosphorylation
      sites of the enzyme. Altogether, the present results suggest that NAK alterations
      may be involved in the pathophysiology of brain damage found in patients in which
      EMA accumulates.

PMID- 23161777
TI  - Palladium(0)-catalyzed enantioselective C-H arylation of cyclopropanes: efficient
      access to functionalized tetrahydroquinolines.

PMID- 23161778
TI  - The role of catalysts and peroxide oxidation in lithium-oxygen batteries.
AB  - A promotor for lithium batteries: nanocrystalline cobalt(II,III) oxide supported
      on graphene enhances the transport kinetics for both oxygen reduction and oxygen
      evolution in the lithium-oxygen cell. On cycling the lithium-oxygen cell, the
      effect of the promoter is, however, eventually overwhelmed by side reactions in
      the cell, such as, the deposition of carbonates.

PMID- 23161775
TI  - MicroRNA profiling in pediatric pilocytic astrocytoma reveals biologically
      relevant targets, including PBX3, NFIB, and METAP2.
AB  - Pilocytic astrocytoma (PA) is a World Health Organization grade I glioma that
      occurs most commonly in children and young adults. Specific genetic alterations
      have been described in PA, but the pathogenesis remains poorly understood. We
      studied microRNA (miRNA) alterations in a large cohort of patients with PA. A
      total of 43 PA, including 35 sporadic grade I PA, 4 neurofibromatosis-1 (NF1)
      associated PA, and 4 PA with pilomyxoid features, as well as 5 nonneoplastic
      brain controls were examined. BRAF fusion status was assessed in most cases. RNA
      was examined using the Agilent Human miRNA Microarray V3 platform. Expression of
      miRNA subsets was validated using quantitative real-time PCR (qRT-PCR) with
      Taqman probes. Validation of predicted protein targets was performed on tissue
      microarrays with the use of immunohistochemistry. We identified a subset of
      miRNAs that were differentially expressed in pediatric PAs versus normal brain
      tissue: 13 miRNAs were underexpressed, and 20 miRNAs were overexpressed in
      tumors. Differences were validated by qRT-PCR in a subset, with mean fold change
      in tumor versus brain of -17 (miR-124), -15 (miR-129), and 19.8 (miR-21).
      Searching for predicted protein targets in Targetscan, we identified a number of
      known and putative oncogenes that were predicted targets of miRNA sets relatively
      underexpressed in PA. Predicted targets with increased expression at the mRNA
      and/or protein level in PA included PBX3, METAP2, and NFIB. A unique miRNA
      profile exists in PA, compared with brain tissue. These miRNAs and their targets
      may play a role in the pathogenesis of PA.

PMID- 23161780
TI  - Memory devices using a mixture of MoS2 and graphene oxide as the active layer.
AB  - A mixed film consisting of 2D MoS2 and graphene oxide (GO) nanosheets is used to
      fabricate memory devices. The conductive MoS2 component in the MoS2-GO film
      increases the film conductivity, thus facilitating oxygen migration in GO. The
      MoS2-GO film-based device exhibits rewritable, nonvolatile, electrical bistable
      switching with low switching voltage (<= 1.5 V) and high ON/OFF current ratio (~
      102).

PMID- 23161779
TI  - 2'-SCF3 uridine-a powerful label for probing structure and function of RNA by 19F
      NMR spectroscopy.
AB  - Fluorishing: the Togni reagent allows efficient synthetic access to fluorine
      labeled RNA molecules. These are in turn highly useful for NMR spectroscopic
      analyses of secondary and tertiary structures, RNA-protein interactions, and
      functionality of riboswitch modules.

PMID- 23161781
TI  - Hydrophobic interaction-mediated capture and release of cancer cells on
      thermoresponsive nanostructured surfaces.

PMID- 23161782
TI  - Does a vascular supercharge improve the clinical outcome for free jejunal
      transfer?
AB  - To clarify whether a supercharged free jejunal transfer would have a different
      clinical outcome from the usual transfer method, we examined clinical data from
      cases of esophago-pharyngeal reconstruction. Fifty-three patients in whom the
      hypopharynx and cervical esophagus was reconstructed with a free jejunal transfer
      were divided into two groups: 19 normal procedures and 34 supercharged. Clinical
      outcomes including intraoperative and postoperative events, complications and
      deglutition were compared statistically. There were no significant differences
      between the groups in terms of the rates of free flap failure, leakage, stenosis,
      drinking status, dysphagia, or operating time. There were no significant
      advantages in clinical outcomes when using a supercharge. However, supercharged
      flaps with an intraoperative arterial thrombosis were all rescued and survived.
      Thus, a supercharge in free flap is not necessary for all cases. Its indication
      should be limited to cases when free flaps are not reliable because of
      intraoperative thrombosis and arterial insufficiency.

PMID- 23161784
TI  - Multifunctional non-viral delivery systems based on conjugated polymers.
AB  - Multifunctional nanomaterials with simultaneous therapeutic and imaging functions
      explore new strategies for the treatment of various diseases. Conjugated polymers
      (CPs) are considered as novel candidates to serve as multifunctional delivery
      systems due to their high fluorescence quantum yield, good photostability, and
      low cytotoxicity. Highly sensitive sensing and imaging properties of CPs are well
      reviewed, while the applications of CPs as delivery systems are rarely covered.
      This feature article mainly focuses on CP-based multifunctional non-viral
      delivery systems for drug, protein, gene, and cell delivery. Promising directions
      for the further development of CP-based delivery systems are also discussed.

PMID- 23161783
TI  - Slit/Robo-mediated chemorepulsion of vagal sensory axons in the fetal gut.
AB  - BACKGROUND: The vagus nerve descends from the brain to the gut during fetal life
      to reach specific targets in the bowel wall. Vagal sensory axons have been shown
      to respond to the axon guidance molecule netrin and to its receptor, deleted in
      colorectal cancer (DCC). As there are regions of the gut wall into which vagal
      axons do and do not extend, it is likely that a combination of attractive and
      repellent cues are involved in how vagal axons reach specific targets. We tested
      the hypothesis that Slit/Robo chemorepulsion can contribute to the restriction of
      vagal sensory axons to specific targets in the gut wall. RESULTS: Transcripts
      encoding Robo1 and Robo2 were expressed in the nodose ganglia throughout
      development and mRNA encoding the Robo ligands Slit1, Slit2, and Slit3 were all
      found in the fetal and adult bowel. Slit2 protein was located in the outer gut
      mesenchyme in regions that partially overlap with the secretion of netrin-1.
      Neurites extending from explanted nodose ganglia were repelled by Slit2.
      CONCLUSIONS: These observations suggest that vagal sensory axons are responsive
      to Slit proteins and are thus repelled by Slits secreted in the gut wall and
      prevented from reaching inappropriate targets.

PMID- 23161785
TI  - Progressive bundling of fibrillin microfibrils into oxytalan fibers in the chick
      presumptive dermis.
AB  - Dorsoventral fibers in the presumptive dermis of the chick limb bud reported
      first by Hurle's group in 1989 are now revealed as bundles of fibrillin
      microfibrils (Isokawa et al., 2004). The bundles, which could be called oxytalan
      fibers at the light microscopic level, are aligned perpendicularly to the
      overlying ectoderm and form a unique fiber array, originating directly from the
      basal lamina. This well-oriented organization is beneficial in examining the
      process of in vivo bundling of microfibrils into oxytalan fibers. In this study,
      sections through the presumptive limb dermis were preferentially prepared from
      chick embryos at Days 4-6 (ED4-6). Immunohistochemically, fibrillin-positive dots
      representing cross-sectioned surfaces of individual fibers, increased in size
      from ED4 to 6, but their number per unit area remained constant.
      Ultrastructurally, a single oxytalan fiber at ED4 consisted of ~15 microfibrils;
      the latter number increased fourfold from ED4 to 5 and threefold from ED5 to 6.
      Oxytalan fibers were all closely associated with mesenchymal cell; notably, the
      fibers at ED5 and 6 were held in a shallow ditch on the cell body or by
      lamellipodial cytoplasmic protrusion. In the sites of cell-fiber adhesion,
      microfibrils in the periphery of an oxytalan fiber appeared to adhere directly or
      by means of short flocculent strands to a nearby cell membrane; the latter showed
      a thickening of plasmalemma and its undercoat, indicating the presence of
      adhesive membrane specification. These findings suggest that the bundling of
      microfibrils is a progressive and closely cell-associated process.

PMID- 23161786
TI  - A self-assembled multiporphyrin cage complex through three different zinc(II)
      center formation under well-balanced aqueous conditions.
AB  - Construction of a self-assembled cage complex through three different Zn(II) 
      centers is achieved using a Zn porphyrin ligand with four 2,2'-bipyridin-5-yl
      (bpy) groups. The multiporphyrin cage encapsulates guest molecules
      unsymmetrically by pi-pi interactions. Well-balanced aqueous conditions, which
      allow the formation of both tris(bpy) and hydrated bis(bpy) Zn(II)  units, result
      in the unsymmetrical yet well-defined supramolecular structure.

PMID- 23161787
TI  - Association between glioma susceptibility loci and tumour pathology defines
      specific molecular etiologies.
AB  - BACKGROUND: Genome-wide association studies have identified single-nucleotide
      polymorphisms (SNPs) at 7 loci influencing glioma risk: rs2736100 (TERT),
      rs11979158 and rs2252586 (EGFR), rs4295627 (CCDC26), rs4977756 (CDKN2A/CDKN2B),
      rs498872 (PHLDB1), and rs6010620 (RTEL1). MATERIALS AND METHODS: We studied the
      relationship among these 7 glioma-risk SNPs and characteristics of tumors from
      1374 patients, including grade, IDH (ie IDH1 or IDH2) mutation, EGFR
      amplification, CDKN2A-p16-INK4a homozygous deletion, 9p and 10q loss, and 1p-19q
      codeletion. RESULTS: rs2736100 (TERT) and rs6010620 (RTEL1) risk alleles were
      associated with high-grade disease, EGFR amplification, CDKN2A-p16-INK4a
      homozygous deletion, and 9p and 10q deletion; rs4295627 (CCDC26) and rs498872
      (PHLDB1) were associated with low-grade disease, IDH mutation, and 1p-19q
      codeletion. In contrast, rs4977756 (CDKN2A/B), rs11979158 (EGFR), and to a lesser
      extent, rs2252586 (EGFR) risk alleles were independent of tumor grade and genetic
      profile. Adjusting for tumor grade showed a significant association between
      rs2736100 and IDH status (P = .01), 10q loss (P = .02); rs4295627 and 1p-19q
      codeletion (P = .04), rs498872 and IDH (P = .02), 9p loss (P = .04), and 10q loss
      (P = .02). Case-control analyses stratified into 4 molecular classes (defined by
      1p-19q status, IDH mutation, and EGFR amplification) showed an association of
      rs4295627 and rs498872 with IDH-mutated gliomas (P < 10(-3)) and rs2736100 and
      rs6010620 with IDH wild-type gliomas (P < 10(-3) and P = .03). CONCLUSION: The
      frequency of EGFR and CDKN2A/B risk alleles were largely independent of tumor
      genetic profile, whereas TERT, RTEL1, CCDC26, and PHLDB1 variants were associated
      with different genetic profiles that annotate distinct molecular pathways. Our
      findings provide further insight into the biological basis of glioma etiology.

PMID- 23161788
TI  - Stimuli-responsive folding and unfolding of a polymer bearing multiple cerium(IV)
      bis(porphyrinate) joints: mechano-imitation of the action of a folding ruler.
AB  - A pivotal guest role: a new porphyrin polymer, poly(PorZn?DD) (pink/purple),
      composed of a porphyrinatozinc and a porphyrin double-decker complex as a
      repeating unit was synthesized. In poly(PorZn?DD), porphyrinatozinc complexes
      recognize a divalent amine (tan/red) to induce an intramolecular pivoting motion
      through the rotation of porphyrin double-decker complexes and the polymer
      undergoes shortening and compaction.

PMID- 23161789
TI  - Cardiac tamponade by myocardial rupture after acute myocardial infarction
      prevented by old thorax trauma.

PMID- 23161790
TI  - Alterations of left ventricular myocardial strain in obese children.
AB  - AIMS: Obesity may have implications in the myocardial structural change, which
      may contribute to mechanical consequences. Using 2D speckle echocardiography, we
      looked for myocardial changes and investigated their relation to obesity,
      inflammation, insulin resistance and physical capacity in children with isolated
      obesity. METHODS AND RESULTS: Standard echocardiography and 2D strain were
      prospectively performed in obese children and compared them with age- and sex
      matched controls. Z-score body mass index (BMI Z-score), ultra-sensitive C
      reactive protein, indices of insulin resistance (HOMA-IR) and metabolic stress
      test were assessed in obese children. Thirty-two consecutive obese patients [age:
      12.8 (8-17) years; 15 males; BMI Z-score: 5.8 [2.05-8.6)] were compared with 32
      controls. Longitudinal strain and circumferential strain were significantly lower
      in the obese group (respectively -18.0 +/- 2.4% vs. -20.6 +/- 2.5%; P = 0.0001
      and -18.2 +/- 3.5% vs. -20.1 +/- 2.3%; P = 0.013), while radial strain did not
      differ. Longitudinal strain was correlated with HOMA-IR (Pearson's rho = -0.39)
      and with the exercise capacity (Pearson's rho = 0.62). In the multivariate
      analysis, after adjusting for age, the mean arterial pressure and left
      ventricular (LV) mass, the BMI Z-score remained independently related to the
      longitudinal and circumferential strain. CONCLUSION: Childhood obesity may be
      associated with an early alteration of the longitudinal and circumferential LV
      strain. These findings have potentially significant clinical implications for the
      outcomes and follow-up of obese children meriting further studies.

PMID- 23161791
TI  - Clinical implication of mitral annular plane systolic excursion for patients with
      cardiovascular disease.
AB  - Mitral annular plane systolic excursion (MAPSE) has been suggested as a parameter
      for left ventricular (LV) function. This review describes the current clinical
      application and potential implications of routinely using MAPSE in patients with
      various cardiovascular diseases. Reduced MAPSE reflects impaired longitudinal
      function and thus provides complementary information to ejection fraction (EF),
      which represents the global result of both longitudinal and circumferential
      contraction. Reduced long-axis deformation results from dysfunctional or stressed
      longitudinal myofibres due to endo- (and potentially epi-) cardial ischaemia,
      fibrosis, or increased wall stress. In patients with aortic stenosis, reduced
      MAPSE is suggestive of subendocardial fibrosis. Moreover, reduced MAPSE could be
      used as a sensitive early marker of LV systolic dysfunction in hypertensive
      patients with normal EF, where compensatory increased circumferential deformation
      might mask the reduced longitudinal deformation. In addition, reduced MAPSE was
      associated with poor prognosis in patients with heart failure, atrial
      fibrillation and post-myocardial infarction as well as in patients with severe
      aortic stenosis undergoing aortic valve replacement. Despite of the routine use
      of newer and more refined echocardiographic technologies nowadays, such as strain
      rate imaging, speckle-tracking imaging, and 3D echocardiography, the use of MAPSE
      measurement is still especially helpful to evaluate LV systolic function in case
      of poor sonographic windows, since good imaging quality is required for most of
      the modern echocardiographic techniques with the exception of tissue Doppler
      imaging.

PMID- 23161792
TI  - Electrochemically driven, electrode-addressable formation of functionalized
      polydopamine films for neural interfaces.
AB  - The electrode-specific formation of polydopamine films is achieved by applying
      positive voltage to the target electrodes at pH 6.0. The functionalization of the
      films is simultaneously carried out by co-depositing dopamine with molecules of
      interest onto the electrode.

PMID- 23161793
TI  - Transient enhancement and spectral narrowing of the photothermal effect of
      plasmonic nanoparticles under pulsed excitation.
AB  - The transient 100-fold enhancement and spectral narrowing to 2 nm of the
      photothermal conversion by solid gold nanospheres under near-infrared excitation
      with a short laser pulse is reported. This non-stationary effect was observed for
      a wide range of optical fluences starting from 10 mJ cm(-2) for single
      nanospheres, their ensembles and aggregated clusters in water, in vitro and in
      vivo.

PMID- 23161794
TI  - Controlled synthesis of hollow Cu2-x Te nanocrystals based on the Kirkendall
      effect and their enhanced CO gas-sensing properties.
AB  - This paper develops a facile solution-based method to synthesize hollow Cu2-x Te
      nanocrystals (NCs) with tunable interior volume based on the Kirkendall effect.
      Transmission electron microscopy images and time-dependent absorption spectra
      reveal the temporal growth process from solid copper nanoparticles to hollow Cu2
      x Te NCs. Furthermore, the as-prepared hollow Cu2-x Te NCs show enhanced
      sensitivity for the detection of carbon monoxide (CO), which is often referred to
      as the "silent killer". The response and recovery time of the as-prepared sensor
      for the detection of 100 ppm CO gas are estimated to be about 21 and 100 s,
      respectively, which are sufficient to render it a promising candidate for
      effective CO gas-sensing applications. Such enhanced performance is achieved
      owing to the small grain size and large specific area of the hollow
      nanostructures. Therefore, the obtained hollow NCs based on the Kirkendall effect
      may have the potential as new functional blocks for high-performance gas sensors.

PMID- 23161795
TI  - Halogenated nucleotide labeling of nascent RNAs reveals dynamic transcription in
      growing pig oocytes.
AB  - BACKGROUND: Germ cells differentiate into oocytes in females and are arrested at
      the first meiotic prophase. However, during arrest, oocytes undergo a growth
      phase leading to a dramatic increase in size, which is under control of
      transcription events. In the current study, we examined the transcriptional
      activity of growing pig oocytes using an immunocytochemical approach. Our data
      showed that fluorouridine (FU), a halogenated nucleotide, can be successfully
      incorporated into synthesizing RNAs and detected using a specific monoclonal
      antibody. RESULTS: Using this method, we identified dynamic changes in
      transcriptional activity patterns in growing pig oocytes. Oocytes obtained from
      small follicles exhibited the highest level of transcription, while at the final
      phase of growth, transcription was no longer detected. These transcriptional
      changes were concomitant with chromatin compaction resulting in a tightly packed
      ring-like chromatin conformation surrounding the nucleolar structure. Also, FU
      incorporation appeared sensitive to the biochemical manipulation of
      transcription, because transcriptional inhibitors induced a decrease in signal
      intensity from FU labeling and transcriptional activation caused an increase in
      FU signal intensity. CONCLUSIONS: Our data collectively support that a direct
      link exists between chromatin configuration and transcriptional activity in pig
      oocytes, and support the suitability of FU for studies on transcription-related
      events in mammalian oocytes.

PMID- 23161796
TI  - Putting aspiration back into thyroid fine-needle biopsy-the re-emerging role of
      vacuum assistance.

PMID- 23161798
TI  - A Mobius antiaromatic complex as a kinetically controlled product in phosphorus
      insertion to a [32]heptaphyrin.
AB  - Singly twisted Mobius antiaromatic [34]heptaphyrin A and doubly twisted Huckel
      aromatic [34]heptaphyrin B were formed by a phosphorus insertion reaction. A
      rearranges thermally to give the more stable B with P=O migration from NNN to
      NNC, and thus A is a rare case of a kinetically controlled Mobius antiaromatic
      molecule.

PMID- 23161797
TI  - Activation of serum/glucocorticoid-induced kinase 1 (SGK1) is important to
      maintain skeletal muscle homeostasis and prevent atrophy.
AB  - Maintaining skeletal muscle mass is essential for general health and prevention
      of disease progression in various neuromuscular conditions. Currently, no
      treatments are available to prevent progressive loss of muscle mass in any of
      these conditions. Hibernating mammals are protected from muscle atrophy despite
      prolonged periods of immobilization and starvation. Here, we describe a mechanism
      underlying muscle preservation and translate it to non-hibernating mammals.
      Although Akt has an established role in skeletal muscle homeostasis, we find that
      serum- and glucocorticoid-inducible kinase 1 (SGK1) regulates muscle mass
      maintenance via downregulation of proteolysis and autophagy as well as increased
      protein synthesis during hibernation. We demonstrate that SGK1 is critical for
      the maintenance of skeletal muscle homeostasis and function in non-hibernating
      mammals in normal and atrophic conditions such as starvation and immobilization.
      Our results identify a novel therapeutic target to combat loss of skeletal muscle
      mass associated with muscle degeneration and atrophy.

PMID- 23161799
TI  - N-methylation of peptides and proteins: an important element for modulating
      biological functions.
AB  - N-Methylation is one of the simplest chemical modifications often occurring in
      peptides and proteins of prokaryotes and higher eukaryotes. Over years of
      evolution, nature has employed N-methylation of peptides as an ingenious
      technique to modulate biological function, often as a mode of survival through
      the production of antibiotics. This small structural change can not only mobilize
      large protein complexes (as in the histone methylation), but also inhibits the
      action of enzymes by selective recognition of protein-protein interaction
      surfaces. In recent years through the advancement in synthetic approaches, the
      potential of N-methylation has begun to be revealed, not only in modulating
      biological activity and selectivity as well as pharmacokinetic properties of
      peptides, but also in delivering novel drugs. Herein, we summarize the current
      knowledge of the versatility of N-methylation in modulating biological,
      structural, and pharmacokinetic properties of peptides.

PMID- 23161800
TI  - Nonenzymatic polymerization of ubiquitin: single-step synthesis and isolation of
      discrete ubiquitin oligomers.
AB  - Linked: a method based on thiol-ene chemistry enables the synthesis and
      purification of ubiquitin oligomers with >=4 units. This approach, which employs
      free-radical polymerization, can be applied towards the synthesis of homogeneous
      Lys6-linked ubiquitin oligomers currently inaccessible by enzymatic methods. By
      using these chains, one can study their roles in the ubiquitin proteasome system
      and the DNA damage response pathway.

PMID- 23161801
TI  - Endovascular treatment of very small ruptured intracranial aneurysms:
      complications, occlusion rates and prediction of outcome.
AB  - OBJECTIVE: To assess predictors of outcome following endovascular treatment of
      small ruptured intracranial aneurysms (SRA). METHODS: Between 2004 and 2011, 91
      patients with SRA (<=3 mm) were treated at our institution. Multivariate analysis
      was carried out to assess predictors of endovascular-related complications,
      aneurysm obliteration (>95%), recanalization and favorable outcome (Glasgow
      Outcome Scale 3-5). RESULTS: Endovascular treatment was aborted in nine of 91
      patients (9.9%). Procedure-related complications occurred in eight of 82 patients
      (9.8%) of which five were transient and three were permanent. Three patients
      (3.7%) undergoing endovascular treatment experienced an intraprocedural aneurysm
      rupture. Three of nine patients (33.3%) treated with stent- or balloon-assisted
      coiling experienced periprocedural complications compared with five of 73
      patients (6.8%) receiving only coils or Onyx (p=0.039). There were no procedural
      deaths or rehemorrhages. Rates of recanalization and retreatment were 18.2% and
      12.7%, respectively. No factors predicted initial occlusion or recanalization. In
      multivariate analysis, pretreatment factors predictive of a favorable outcome
      included younger age (OR 0.94; 95% CI 0.91 to 0.99, p=0.017), larger aneurysm
      size (OR 3.4; 95% CI 1.02 to 11.11, p=0.045), Hunt and Hess grade (OR 0.38; 95%
      CI 0.19 to 0.75, p=0.005) and location (OR 5.12; 95% CI 1.29 to 20.25, p=0.02).
      When assessing treatment and post-treatment variables, vasospasm was the only
      additional covariate predictive of a poor outcome (OR 5.90; 95% CI 1.34 to
      25.93,p=0.019). CONCLUSIONS: Most patients with SRA can be treated with
      endovascular therapy and have limited complications. Overall predictors of
      outcome for patients undergoing endovascular treatment of SRA include age,
      aneurysm size, Hunt and Hess grade, location and post-treatment vasospasm.

PMID- 23161802
TI  - Synthesis and photovoltaic effect in dithieno[2,3-d:2',3'-d']benzo[1,2-b:4,5
      b']dithiophene-based conjugated polymers.

PMID- 23161803
TI  - Equarin is involved in cell adhesion by means of heparan sulfate proteoglycan
      during lens development.
AB  - BACKGROUND: Adhesion molecules are known to be instructive for both development
      and differentiation. During lens differentiation, epithelial cells undergo
      vertical elongation, with the anterior and posterior tips of the elongating fiber
      cells sliding along the epithelium and capsule, respectively. These cellular
      processes are highly coordinated through cell adhesive interactions, actin
      cytoskeletal reorganization and contractile force generation. Alterations in
      extracellular matrix composition that interfere with these interactions can lead
      to defects that alter tissue morphogenesis and the state of differentiation. We
      have demonstrated that Equarin, which is a secreted molecule expressed in the
      equator region of the lens, plays an important role in chick lens fiber
      differentiation through fibroblast growth factor signaling. RESULTS: Here, we
      explored the function of Equarin in chick lens cell adhesion. Equarin protein was
      expressed in the extracellular region of lens differentiating cells. We found
      that Equarin promoted lens cell adhesion through heparan sulfate proteoglycan. By
      biochemical analysis, we found that Equarin directly binds syndecan-3, which
      displayed a similar expression pattern to Equarin. Overexpression of Equarin
      resulted in altered actin localization. CONCLUSIONS: Equarin is involved in cell
      adhesion during fiber differentiation and development.

PMID- 23161804
TI  - Enantiomeric discrimination of isoxazoline fused beta-amino acid derivatives
      using (18-crown-6)-2,3,11,12-tetracarboxylic acid as a chiral NMR solvating
      agent.
AB  - (18-Crown-6)-2,3,11,12-tetracarboxylic acid is a useful chiral NMR solvating
      agent for isoxazoline-fused beta-amino acid derivatives. Isoxazoline substrates
      are analyzed as their hydrochloride salts in methanol-d(4). The crown ether and
      substrate associate through the formation of three hydrogen bonds between the
      protonated amine and crown ether oxygen atoms. Enantiomeric discrimination is
      observed for two or more resonances of every substrate. At least one of these
      resonances is free of overlap with other resonances in the spectrum and has large
      enough enantiomeric discrimination to enable the determination of enantiomeric
      purity. 2D COSY methods can be used to identify additional resonances that
      exhibit enantiomeric discrimination in the NMR spectrum.

PMID- 23161805
TI  - Strategy for the creation of clinical grade hESC line banks that HLA-match a
      target population.
AB  - Here, we describe a pre-derivation embryo haplotyping strategy that we developed
      in order to maximize the efficiency and minimize the costs of establishing banks
      of clinical grade hESC lines in which human leukocyte antigen (HLA) haplotypes
      match a significant proportion of the population. Using whole genome
      amplification followed by medium resolution HLA typing using PCR amplification
      with sequence-specific primers (PCR-SSP), we have typed the parents, embryos and
      hESC lines from three families as well as our eight clinical grade hESC lines and
      shown that this technical approach is rapid, reliable and accurate. By employing
      this pre-derivation strategy where, based on HLA match, embryos are selected for
      a GMP route on day 3-4 of development, we would have drastically reduced our cGMP
      laboratory running costs.

PMID- 23161806
TI  - UHPLC/ESI-Q-TOF-MS method for the measurement of dopamine in rodent striatal
      tissue: a comparative effects of intranasal administration of ropinirole solution
      over nanoemulsion.
AB  - An ultra high performance liquid chromatography-electrospray ionization-tandem
      mass spectrometric method (UHPLC/ESI-Q-TOF-MS) for the analysis of dopamine (DA)
      in Wistar rat brain homogenate has been developed and validated. The
      chromatographic separation was achieved on a Waters ACQUITY UPLCTM BEH C18 (100.0
      mm * 2.1 mm; 1.7 um) column using isocratic mobile phase, consisting of
      acetonitrile and Formic acid (0.1% w/v) (10: 90; v/v), at a flow rate of 0.15 ml
      min(-1) . The transitions occurred at m/z 154.04 -> 137.006 for DA, and m/z
      184.204 -> 166.08 for the internal standard. The recovery of the analytes from
      Wistar rat brain homogenate was optimized using liquid-liquid extraction
      technique (LLE) in ethyl acetate. The total run time was 3.5 min and the elution
      of DA occurred at 1.44 +/- 0.05 min. The linear dynamic range was established
      over the concentration range 75-750 ng mL(-1) (r(2) ; 0.9921 +/- 0.0005) for DA.
      The intra-assay and inter-assay accuracy in terms of % CV was in the range 0.73
      2.80. The lower limit of detection (LOD) and quantitation (LOQ) for DA was 0.278
      and 0.844 ng mL(-1) , respectively. Analytes were stable under various conditions
      (in autosampler, during freeze-thaw, at room temperature, and under deep-freeze
      conditions). The developed method was successfully applied for in vivo profiling
      in rodents.

PMID- 23161807
TI  - Success rates and procedure times of oesophageal temperature probe insertion for
      therapeutic hypothermia treatment of cardiac arrest according to insertion
      methods in the emergency department.
AB  - PURPOSE: Therapeutic hypothermia has become the standard treatment for
      unconscious patients in cardiac arrest. Although various body parts, including
      the oesophagus, rectum, bladder and tympanum, can be used for measurement of the
      core temperature, the oesophageal temperature is preferred because of its
      accuracy and stability. We first investigated the success rate and procedure time
      of oesophageal temperature probe (ETP) insertion according to the insertion
      method. METHODS: The conventional method involved blind insertion through nasal
      orifices. The alternative method was insertion with Magill's forceps or long
      forceps under visualisation using a direct laryngoscope. The new method was
      performed as follows: (1) insertion of another endotracheal tube (ETT) orally
      into the oesophagus; (2) insertion of a temperature probe into the hole of the
      ETT; (3) removal of the ETT. To compare the success rates and procedure times
      according to the insertion method, we collected data retrospectively from the
      prospective Samsung Medical Centre hypothermia database and medical records.
      RESULTS: A total of 91 cases were examined. Insertion was performed using the
      conventional method in 36 cases, the alternative method in 26, and the new method
      in 29. Rates of success on the first attempt were 63.9%, 65.4% and 100%, and
      procedure times were 33.2 +/- 13.6, 33.3 +/- 17.8 and 27.0 +/- 7.9 min, for the
      conventional, alternative and new methods, respectively. The initial success
      rates and procedure times were significantly different among the three groups
      (p<0.01). CONCLUSIONS: The new ETP insertion method had a better first attempt
      success rate than the conventional method and the alternative method.

PMID- 23161808
TI  - Haemostatic dressings in prehospital care.
AB  - Massive haemorrhage still accounts for up to 40% of mortality after traumatic
      injury. The importance of limiting blood loss after injury in order to prevent
      its associated complications has led to rapid advances in the development of
      dressings for haemostatic control. Driven by recent military conflicts, there is
      increasing evidence to support their role in the civilian prehospital care
      environment. This review aims to summarise the key characteristics of the
      haemostatic dressings currently available on the market and provide an
      educational review of the published literature that supports their use. Medline
      and Embase were searched from start to January 2012. Other sources included both
      manufacturer and military publications. Agents not designed for use in
      prehospital care or that have been removed from the market due to significant
      safety concerns were excluded. The dressings reviewed have differing mechanisms
      of action. Mineral based dressings are potent activators of the intrinsic
      clotting cascade resulting in clot formation. Chitosan based dressings achieve
      haemostasis by adhering to damaged tissues and creating a physical barrier to
      further bleeding. Acetylated glucosamine dressings work via a combination of
      platelet and clotting cascade activation, agglutination of red blood cells and
      local vasoconstriction. Anecdotal reports strongly support the use of haemostatic
      dressings when bleeding cannot be controlled using pressure dressings alone;
      however, current research focuses on studies conducted using animal models. There
      is a paucity of published clinical literature that provides an evidence base for
      the use of one type of haemostatic dressing over another in humans. 

PMID- 23161809
TI  - Asymmetric Bronsted acid catalyzed cycloadditions--efficient enantioselective
      synthesis of pyrazolidines, pyrazolines, and 1,3-diamines from N-acyl hyrazones
      and alkenes.

PMID- 23161811
TI  - Saccharomyces boulardii viability and efficacy in horses with antimicrobial
      induced diarrhoea.
AB  - Saccharomyces boulardii has been successfully used in the prevention and
      treatment of antimicrobial-associated diarrhoea in humans. We hypothesised that a
      viable, dried lyophilised preparation of S boulardii would survive in the
      gastrointestinal tract of horses with antimicrobial-associated enterocolitis, and
      significantly decrease the duration of diarrhoea. Twenty-one horses, over one
      year of age, with antimicrobial-associated diarrhoea of up to 72 hours duration,
      were consecutively randomised in a controlled prospective study. The treatment
      group received S boulardii (25 g, orally, every 12 hours) until the cessation of
      clinical signs. S boulardii was successfully cultured in 58.3 per cent of
      treatment horses on day 3. No statistically significant differences were found in
      days to return to normal faecal consistency; resolution of watery diarrhoea;
      return to normal heart rate, respiratory rate and temperature; resolution of
      leucopaenia; attitude improvement; appetite improvement; and survival at
      discharge. This is the first study to demonstrate survival of S boulardii in
      horses with gastrointestinal illness. Further study of the efficacy and safety of
      S boulardii in horses with antimicrobial-associated diarrhoea in a larger group
      is warranted.

PMID- 23161812
TI  - Challenges and proposed solutions for more accurate serological diagnosis of
      equine infectious anaemia.
AB  - Serological diagnosis of equine infectious anaemia virus (EIAV) infections has
      depended mainly on the agar gel immunodiffusion test (AGIDT). This study
      documents the presence of EIAV genetic sequences in a number of persistently
      infected horses and mules whose serums were interpreted as negative/equivocal on
      AGIDT, but positive on more than one ELISA test and in immunoblot tests.
      Strategies designed to take advantage of the combined strengths of the ELISA and
      AGIDT are shown effective in a national surveillance program for EIA in Italy
      where 17 per cent (25/149) of the equids considered to be infected with EIAV on
      combined/comparative serological data had reactions in the AGIDT that were
      interpreted as negative or equivocal. These data document the benefits of using a
      three-tiered laboratory system for the diagnosis of EIA. Although the ELISA-first
      strategy introduces some confusing results, the discovery of up to 20 per cent
      more cases of EIA makes it compelling. In our opinion, it is better and more
      defensible to find two samples in 1000 with resolvable but falsely positive ELISA
      tests for EIA than to release two to three horses in 10,000 with falsely negative
      test results for EIA (the rates seen in the Italian surveillance presented here).

PMID- 23161813
TI  - Total synthesis and stereochemical revision of the chlorinated sesquiterpene (+/
      )-gomerone c.
AB  - Revised: the total synthesis of gomerone C results in revision of the
      stereochemical assignment at C3. The synthetic strategy relies on a late-stage
      Conia-ene reaction, which efficiently forms the bicyclo[3.2.1]octane containing
      the bridgehead chloride and generates an exocyclic olefin, which can be used as a
      flexible handle for further elaboration. The two contiguous quaternary centers
      are installed by means of a Diels-Alder reaction.

PMID- 23161815
TI  - Identification and differentiation of methcathinone analogs by gas chromatography
      mass spectrometry.
AB  - To overcome a number of challenges involved in analyzing methcathinone (MC)
      analogues, we performed gas chromatography-mass spectrometry (GC-MS) analysis,
      including sample preparation, of nine MC analogues - 4-methylmethcathinone, three
      positional isomers of fluoromethcathinones, 4-methoxymethcathinone, N
      ethylcathinone, N,N-dimethylcathinone, buphedrone, and pentedrone. The MC
      analogues underwent dehydrogenation when the free bases were analyzed using
      splitless injection. Most of this thermal degradation was prevented using split
      injection. This indicated that a shorter residence time in the hot injector
      prevented decomposition. Uniquely, 2-fluoromethcathinone degraded to another
      product in a process that could not be prevented by the split injection.
      Replacing the liner with a new, clean one was also effective in preventing
      thermal degradation. Most of the analytes showed a substantial loss (>30%) when
      the free base solution in ethyl acetate was evaporated under a nitrogen stream.
      Adding a small amount of dimethylformamide as a solvent keeper had a noticeable
      effect, but it did not completely prevent the loss. Three positional isomers of
      fluoromethcathinones were separated with baseline resolution by
      heptafluorobutyrylation with a slow column heating rate (8  degrees C/min) using
      a non-polar DB-5 ms capillary column. These results will be useful for the
      forensic analysis of MC analogues in confiscated materials.

PMID- 23161816
TI  - Identification of the biosynthetic gene cluster and regulatory cascade for the
      synergistic antibacterial antibiotics griseoviridin and viridogrisein in
      Streptomyces griseoviridis.
AB  - Griseoviridin (GV) and viridogrisein (VG, also referred to as etamycin), produced
      by Streptomyces griseoviridis, are two chemically unrelated compounds belonging
      to the streptogramin family. Both of these natural products demonstrate broad
      spectrum antibacterial activity and constitute excellent candidates for future
      drug development. To elucidate the biosynthetic machinery associated with
      production of these two unique antibiotics, the gene cluster responsible for both
      GV and VG production was identified within the Streptomyces griseoviridis genome
      and characterized, and its function in GV and VG biosynthesis was confirmed by
      inactivation of 30 genes and complementation experiments. This sgv gene cluster
      is localized to a 105 kb DNA region that consists of 36 open reading frames
      (ORFs), including four nonribosomal peptide synthetases (NRPSs) for VG
      biosynthesis and a set of hybrid polyketide synthases (PKS)-NRPSs with a discrete
      acyltransferase (AT), SgvQ, to assemble the GV backbone. The enzyme encoding
      genes for VG versus GV biosynthesis are separated into distinct "halves" of the
      cluster. A series of four genes: sgvA, sgvB, sgvC, and sgvK, were found
      downstream of the PKS-NRPS; these likely code for construction of a gamma
      butyrolactone (GBL)-like molecule. GBLs and the corresponding GBL receptor
      systems are the highest ranked regulators that are able to coordinate the two
      streptomyces antibiotic regulatory protein (SARP) family positive regulators
      SgvR2 and SgvR3; both are key biosynthetic activators. Models of GV, VG, and GBL
      biosynthesis were proposed by using functional gene assignments, determined on
      the basis of bioinformatics analysis and further supported by in vivo gene
      inactivation experiments. Overall, this work provides new insights into the
      biosyntheses of the GV and VG streptogramins that are potentially applicable to a
      host of combinatorial biosynthetic scenarios.

PMID- 23161818
TI  - Construction of Pourbaix diagrams for ruthenium-based water-oxidation catalysts
      by density functional theory.

PMID- 23161819
TI  - Hydrothermal synthesis of pencil-like SAPO-5 and observation of its reversed
      crystal-growth process.
AB  - SAPO-5 with a novel hexagonal pencil-like morphology was hydrothermally
      synthesized from hydrogels that contain triethylamine and high concentrations of
      acetic acid at 180  degrees C for 48 h. The effect of the acetic acid
      concentration was examined and indicated that usage of a high concentration of
      acetic acid is crucial to the synthesis of SAPO-5 with a pencil-like morphology.
      The time-dependent growth process of novel SAPO-5 was observed by scanning
      electron microscopy with the aid of acid treatment to remove the amorphous
      materials for clearer observation. The samples were also characterized by X-ray
      diffraction and Fourier-transform infrared spectroscopy. The results show that
      the crystal growth at the early stage follows the reversed crystal-growth route.
      First, the crystallization occurs on the surface of the aggregated amorphous
      ellipsoidal particles to form a hexagonal prism crystal shell with the
      encapsulation of amorphous materials. Then, the amorphous materials wrapped
      inside start to grow to a hexagonal prism inside the hollow larger hexagonal
      prism shell. Finally, the interior hexagonal prism continues to grow to the two
      ends with its length beyond that of the larger one by means of the Ostwald
      ripening process, thus forming the pencil-like crystal.

PMID- 23161817
TI  - Microfluidic tools for developmental studies of small model organisms--nematodes,
      fruit flies, and zebrafish.
AB  - Studying the genetics of development with small model organisms such as the
      zebrafish (Danio Rerio), the fruit fly (Drosophila melanogaster), and the soil
      dwelling nematode (Caenorhabditis elegans), provide unique opportunities for
      understanding related processes and diseases in humans. These model organisms
      also have potential for use in drug discovery and toxicity-screening
      applications. There have been sweeping developments in microfabrication and
      microfluidic technologies for manipulating and imaging small objects, including
      small model organisms, which allow high-throughput quantitative biological
      studies. Here, we review recent progress in microfluidic tools able to manipulate
      small organisms and project future directions and applications of these
      techniques and technologies.

PMID- 23161820
TI  - Synthesis of F16 conjugated with 5-fluorouracil and biophysical investigation of
      its interaction with bovine serum albumin by a spectroscopic and molecular
      modeling approach.
AB  - 5-Fluorouracil (5-FU) has been widely used as a chemotherapy agent in the
      treatment of many types of solid tumors. Investigation of its antimetabolites led
      to the development of an entire class of fluorinated pyrimidines. However, the
      toxicity profile associated with 5-FU is significant and includes diarrhea,
      mucositis, hand-foot syndrome and myelosuppression. In aiming at reducing of the
      side effects of 5-FU, we have designed and synthesized delocalized lipophilic
      cations (DLCs) as a vehicle for the delivery of 5-FU. DLCs accumulate selectively
      in the mitochondria of cancer cells because of the high mitochondrial
      transmembrane potential (DeltaPsim). Many DLCs exhibited anti-cancer efficacy and
      were explored as potential anti-cancer drugs based on their selective
      accumulation in the mitochondria of cancer cells. F16, the DLC we used as a
      vehicle, is a small molecule that selectively inhibits tumor cell growth and
      dissipates mitochondrial membrane potential. The binding of the conjugate F16-5
      FU to bovine serum albumin (BSA) was investigated using spectroscopic and
      molecular modeling approaches. Fluorescence quenching constants were determined
      using the Stern-Volmer equation to provide a measure of the binding affinity
      between F16-5-FU and BSA. The activation energy of the interaction between F16-5
      FU and BSA was calculated and the unusually high value was discussed in terms of
      the special structural block indicated by the molecular modeling approach.
      Molecular modeling showed that F16-5-FU binds to human serum albumin in site II,
      which is consistent with the results of site-competitive replacement experiments.
      It is suggested that hydrophobic and polar forces played important roles in the
      binding reaction, in accordance with the results of thermodynamic experiments.

PMID- 23161821
TI  - [(MU-H)3Re3(CO)9(eta2,eta2,eta2-Sc2C2@C(3v)(8)-C(82))]: face-capping cluster
      complex of an endohedral fullerene.
AB  - Like a miniature trophy, the complex pictured was obtained as the sole product
      from the reaction of Sc(2)C(2)@C(3v)(8)-C(82) and [(MU-H)(3)Re(3)(CO)(11)(NCMe)]
      and characterized by IR, visible/near-infrared, and NMR spectroscopy, mass
      spectrometry, and X-ray diffraction. Coordination of the Re(3) cluster to the
      unique hexagon oriented perpendicular to the C(3) axis of the fullerene core
      altered the geometry and electronic properties of Sc(2)C(2)@C(3v)(8)-C(82).

PMID- 23161822
TI  - Modulation of lumen formation by microgeometrical bioactive cues and migration
      mode of actin machinery.
AB  - How endothelial cells (ECs) express the particular filopodial or lamellipodial
      form of the actin machinery is critical to understanding EC functions such as
      angiogenesis and sprouting. It is not known how these mechanisms coordinately
      promote lumen formation of ECs. Here, adhesion molecules (RGD peptides) and
      inductor molecules (BMP-2 mimetic peptides) are micropatterned onto polymer
      surfaces by a photolithographic technique to induce filopodial and lamellipodial
      migration modes. Firstly, the effects of peptide microgeometrical distribution on
      EC adhesion, orientation and morphogenesis are evaluated. Large micropatterns
      (100 MUm) promote EC orientation without lumen formation, whereas small
      micropatterns (10-50 MUm) elicit a collective cell organization and induce EC
      lumen formation, in the case of RGD peptides. Secondly, the correlation between
      EC actin machinery expression and EC self-assembly into lumen formation is
      addressed. Only the filopodial migration mode (mimicked by RGD) but not
      lamellipodial migration mode (mimicked by BMP-2) promotes EC lumen formation.
      This work gives a new concept for the design of biomaterials for tissue
      engineering and may provide new insight for angiogenesis inhibition on tumors.

PMID- 23161823
TI  - Broad-spectrum antimicrobial and biofilm-disrupting hydrogels: stereocomplex
      driven supramolecular assemblies.
AB  - Fighting the resistance: biodegradable and injectable/moldable hydrogels with
      hierarchical nanostructures were made with broad-spectrum antimicrobial
      activities and biofilm-disruption capability. They demonstrate no cytotoxicity in
      vitro, and show excellent skin biocompatibility in animals. These hydrogels have
      great potential for clinical use in prevention and treatment of various multidrug
      resistant infections.

PMID- 23161824
TI  - Light-controlled toxicity of engineered amyloid beta-peptides.
AB  - Aggregation of amyloid beta (Abeta(1-42)), causing toxicity, is a critical step
      in Alzheimer's disease (AD). AD studies are difficult to compare because Abeta(1
      42) aggregation is poorly controllable under physiological conditions. To control
      aggregation and toxicity, we engineered light-switchable Abeta(1-42) analogues
      that enable controllable conversion of nontoxic fibrils into toxic oligomers
      simply by illumination.

PMID- 23161825
TI  - Deep desulfurization by amphiphilic lanthanide-containing polyoxometalates in
      ionic-liquid emulsion systems under mild conditions.
AB  - Amphiphilic lanthanide-containing polyoxometalates (POMs) were prepared by
      surfactant encapsulation. Investigation of these lanthanide-containing POMs in
      oxidative desulfurization (ODS) showed that highly efficient deep desulfurization
      could be achieved in only 14 min with 100% conversion of dibenzothiophene under
      mild conditions by using (DDA)(9)LaW(10)/[omim]PF(6)
      (DDA=dimethyldioctadecylammonium, omim=1-octyl-3-methyl-imidazolium) in the
      presence of H(2) O(2) . Furthermore, deep desulfurization proceeds smoothly in
      model oil with an S content as low as 50 ppm. A scaled-up experiment in which the
      volume of model oil was increased from 5 to 1000 mL with S content of 1000 ppm
      indicated that about 99% sulfur removal can be achieved in 40 mins in an ionic
      liquid emulsion system. To the best of our knowledge, the
      (DDA)(9)LaW(10)/[omim]PF(6) catalyst system with H(2)O(2) as oxidant is one of
      the most efficient desulfurization systems reported so far.

PMID- 23161827
TI  - Bioreactors in tissue engineering - principles, applications and commercial
      constraints.
AB  - Bioreactor technology is vital for tissue engineering. Usually, bioreactors are
      used to provide a tissue-specific physiological in vitro environment during
      tissue maturation. In addition to this most obvious application, bioreactors have
      the potential to improve the efficiency of the overall tissue-engineering
      concept. To date, a variety of bioreactor systems for tissue-specific
      applications have been developed. Of these, some systems are already commercially
      available. With bioreactor technology, various functional tissues of different
      types were generated and cultured in vitro. Nevertheless, these efforts and
      achievements alone have not yet led to many clinically successful tissue
      engineered implants. We review possible applications for bioreactor systems
      within a tissue-engineering process and present basic principles and requirements
      for bioreactor development. Moreover, the use of bioreactor systems for the
      expansion of clinically relevant cell types is addressed. In contrast to cell
      expansion, for the generation of functional three-dimensional tissue equivalents,
      additional physical cues must be provided. Therefore, bioreactors for
      musculoskeletal tissue engineering are discussed. Finally, bioreactor technology
      is reviewed in the context of commercial constraints.

PMID- 23161826
TI  - Mutations in SYNGAP1 cause intellectual disability, autism, and a specific form
      of epilepsy by inducing haploinsufficiency.
AB  - De novo mutations in SYNGAP1, which codes for a RAS/RAP GTP-activating protein,
      cause nonsyndromic intellectual disability (NSID). All disease-causing point
      mutations identified until now in SYNGAP1 are truncating, raising the possibility
      of an association between this type of mutations and NSID. Here, we report the
      identification of the first pathogenic missense mutations (c.1084T>C [p.W362R],
      c.1685C>T [p.P562L]) and three novel truncating mutations (c.283dupC
      [p.H95PfsX5], c.2212_2213del [p.S738X], and (c.2184del [p.N729TfsX31]) in SYNGAP1
      in patients with NSID. A subset of these patients also showed ataxia, autism, and
      a specific form of generalized epilepsy that can be refractory to treatment. All
      of these mutations occurred de novo, except c.283dupC, which was inherited from a
      father who is a mosaic. Biolistic transfection of wild-type SYNGAP1 in pyramidal
      cells from cortical organotypic cultures significantly reduced activity-dependent
      phosphorylated extracellular signal-regulated kinase (pERK) levels. In contrast,
      constructs expressing p.W362R, p.P562L, or the previously described p.R579X had
      no significant effect on pERK levels. These experiments suggest that the de novo
      missense mutations, p.R579X, and possibly all the other truncating mutations in
      SYNGAP1 result in a loss of its function. Moreover, our study confirms the
      involvement of SYNGAP1 in autism while providing novel insight into the epileptic
      manifestations associated with its disruption.

PMID- 23161828
TI  - Direct determination of sitagliptin in pharmaceutical formulations and its
      determination in urine after solid-phase extraction by spectrofluorimetry.
AB  - The fluorescence characteristics of sitagliptin phosphate were used to develop a
      methodology that allowed its determination in pharmaceutical formulations and
      urine samples; under the studied conditions, limits of determination and
      quantification of 0.25 and, respectively, 0.85 mg/L were achieved. Linear
      correlation between fluorescence analytical signal and sitagliptin concentration
      was achieved up to 10.0 mg/L. The method was considered selective for sitagliptin
      determination in pharmaceutical formulations because no interferences due to
      excipients present in considered matrix were observed (as demonstrated by
      recovery tests comparing analytical and addition curves). When the method was
      applied to urine samples, Interferences related to the matrix were observed,
      which made a solid-phase extraction system necessary. The use of calibration was
      possible only by applying the standard addition method.

PMID- 23161829
TI  - Total synthesis of (-)-acetylaranotin.
AB  - The key step in this total synthesis of (-)-acetylaranotin is the efficient
      formation of the characteristic dihydrooxepine ring from cyclohexenone through an
      unusual vinylogous Rubottom oxidation and a regioselective Baeyer-Villiger
      oxidation. (-)-Acetylaranotin is obtained in 22 steps from commercially available
      L-Cbz-tyrosine (Cbz=benzyloxycarbonyl).

PMID- 23161830
TI  - Adenocarcinoma cells in effusion cytology as a diagnostic pitfall with potential
      impact on clinical management: a case report with brief review of immunomarkers.
AB  - Distinguishing metastatic carcinoma cells from reactive mesothelial cells in
      effusion samples is often challenging based on morphology alone. Metastatic
      carcinoma cells in fluid samples may mimic reactive mesothelial cells due to
      overlapping cytological features. We report a case of a pleural effusion in a 51
      year-old female patient with a medical history significant for bilateral ovarian
      tumors and peritoneal implants diagnosed as serous tumor of borderline malignant
      potential. The effusion was composed almost entirely of adenocarcinoma cells that
      morphologically mimicked reactive mesothelial cells. The diagnosis of metastatic
      adenocarcinoma was made after a wide immunostaining panel of antibodies.
      Recognizing metastatic adenocarcinoma cells in effusion samples can be
      challenging and an accurate diagnosis may have significant impact on clinical
      management as demonstrated by this case.

PMID- 23161831
TI  - Oxygen migration pathways in NO-bound truncated hemoglobin.
AB  - Atomistic simulations of dioxygen (O(2)) dynamics and migration in nitric oxide
      bound truncated Hemoglobin N (trHbN) of Mycobacterium tuberculosis are reported.
      From more than 100 ns of simulations the connectivity network involving the
      metastable states for localization of the O(2) ligand is built and analyzed. It
      is found that channel I is the primary entrance point for O(2) whereas channel II
      is predominantly an exit path although access to the protein active site is also
      possible. For O(2) a new site compared to nitric oxide, from which reaction with
      the heme group can occur, was found. As this site is close to the heme iron, it
      could play an important role in the dioxygenation mechanism as O(2) can remain
      there for hundreds of picoseconds after which it can eventually leave the
      protein, while NO is localized in Xe2. The present study supports recent
      experimental work which proposed that O(2) docks in alternative pockets than Xe
      close to the reactive site. Similar to other proteins, a phenylalanine residue
      (Phe62) plays the role of a gate along the access route in channel I. The most
      highly connected site is the Xe3 pocket which is a "hub" and free energy barriers
      between the different metastable states are ~1.5 kcal mol(-1) which allows facile
      O(2) migration within the protein.

PMID- 23161833
TI  - Rhodium-catalyzed regio-, diastereo-, and enantioselective [2+2+2] cycloaddition
      of 1,6-enynes with acrylamides.
AB  - Ring ring: annulated cyclohexenes were synthesized by using the title reaction
      with the cationic rhodium(I)/(R)-H(8) -binap complex as a catalyst. In this
      catalysis, regioselective insertion of the acrylamide into a rhodacyclopentene
      intermediate and the coordination of the carbonyl group of the acrylamide to the
      cationic rhodium center suppress the undesired beta-hydride elimination.

PMID- 23161834
TI  - Continuous microwire patterns dominated by controllable rupture of liquid films.
AB  - Controllable microwire patterns are prepared by dominating the rupture of liquid
      films. Regular rhombic-shaped micropillar arrays serve as wetting defects to pin
      or depin liquids, yielding continuous, herringbone, bead-shaped polystyrene
      microwire patterns or bead arrays. The results provide a deeper understanding of
      the controllable rupture of liquid films and offer a general strategy for the
      organization of polymers into structures needed for wiring, interconnects, and
      functional devices for future microfabrication.

PMID- 23161832
TI  - Raman spectroscopy in biomedicine - non-invasive in vitro analysis of cells and
      extracellular matrix components in tissues.
AB  - Raman spectroscopy is an established laser-based technology for the quality
      assurance of pharmaceutical products. Over the past few years, Raman spectroscopy
      has become a powerful diagnostic tool in the life sciences. Raman spectra allow
      assessment of the overall molecular constitution of biological samples, based on
      specific signals from proteins, nucleic acids, lipids, carbohydrates, and
      inorganic crystals. Measurements are non-invasive and do not require sample
      processing, making Raman spectroscopy a reliable and robust method with numerous
      applications in biomedicine. Moreover, Raman spectroscopy allows the highly
      sensitive discrimination of bacteria. Rama spectra retain information on
      continuous metabolic processes and kinetics such as lipid storage and recombinant
      protein production. Raman spectra are specific for each cell type and provide
      additional information on cell viability, differentiation status, and
      tumorigenicity. In tissues, Raman spectroscopy can detect major extracellular
      matrix components and their secondary structures. Furthermore, the non-invasive
      characterization of healthy and pathological tissues as well as quality control
      and process monitoring of in vitro-engineered matrix is possible. This review
      provides comprehensive insight to the current progress in expanding the
      applicability of Raman spectroscopy for the characterization of living cells and
      tissues, and serves as a good reference point for those starting in the field.

PMID- 23161836
TI  - Confirmation of an early postulate: B-C-B two-electron-three-center bonding in
      organo(hydro)boranes.
AB  - Finally, boron did it too: The first example of a dimeric organyl(hydro)borane
      with a B-B-bridging aryl ring has been elucidated (see picture; B green/blue, C
      black/gray). It features a B-C-B two-electron-three-center bond and a largely
      unperturbed aromatic pi-electron system.

PMID- 23161835
TI  - Potent inhibitors of malarial aspartic proteases, the plasmepsins, by
      hydroformylation of substituted 7-azanorbornenes.
AB  - The increasing prevalence of multidrug-resistant strains of the malarial parasite
      Plasmodium falciparum requires the urgent development of new therapeutic agents
      with novel modes of action. The vacuolar malarial aspartic proteases plasmepsin
      (PM) I, II, and IV are involved in hemoglobin degradation and play a central role
      in the growth and maturation of the parasite in the human host. We report the
      structure-based design, synthesis, and in vitro evaluation of a new generation of
      PM inhibitors featuring a highly decorated 7-azabicyclo[2.2.1]heptane core. While
      this protonated central core addresses the catalytic Asp dyad, three substituents
      bind to the flap, the S1/S3, and the S1' pockets of the enzymes. A
      hydroformylation reaction is the key synthetic step for the introduction of the
      new vector reaching into the S1' pocket. The configuration of the racemic ligands
      was confirmed by extensive NMR and X-ray crystallographic analysis. In vitro
      biological assays revealed high potency of the new inhibitors against the three
      plasmepsins (IC(50)  values down to 6 nM) and good selectivity towards the
      closely related human cathepsins D and E. The occupancy of the S1' pocket makes
      an essential contribution to the gain in binding affinity and selectivity, which
      is particularly large in the case of the PM IV enzyme. Designing non-peptidic
      ligands for PM II is a valid route to generate compounds that inhibit the entire
      family of vacuolar plasmepsins.

PMID- 23161837
TI  - Functional characterization of novel mutations affecting survivin (BIRC5)
      mediated therapy resistance in head and neck cancer patients.
AB  - Survivin (BIRC5) is an acknowledged cancer therapy-resistance factor and
      overexpressed in head and neck squamous cell carcinomas (HNSCC). Driven by its
      nuclear export signal (NES), Survivin shuttles between the nucleus and the
      cytoplasm, and is detectable in both cellular compartments in tumor biopsies.
      Although predominantly nuclear Survivin is considered a favorable prognostic
      disease marker for HNSCC patients, the underlying molecular mechanisms are not
      resolved. Hence, we performed immunohistochemical and mutational analyses using
      laser capture microdissection on HNSCC biopsies from patients displaying high
      levels of nuclear Survivin. We found somatic BIRC5 mutations, c.278T>C
      (p.Phe93Ser), c.292C>T (p.Leu98Phe), and c.288A>G (silent), in tumor cells, but
      not in corresponding normal tissues. Comprehensive functional characterization of
      the Survivin mutants by ectopic expression and microinjection experiments
      revealed that p.Phe93Ser, but not p.Leu98Phe inactivated Survivin's NES, resulted
      in a predominantly nuclear protein, and attenuated Survivin's dual cytoprotective
      activity against chemoradiation-induced apoptosis. Notably, in
      xenotransplantation studies, HNSCC cells containing the p.Phe93Ser mutation
      responded significantly better to cisplatin-based chemotherapy. Collectively, our
      results underline the disease relevance of Survivin's nucleocytoplasmic
      transport, and provide first evidence that genetic inactivation of Survivin's NES
      may account for predominantly nuclear Survivin and increased therapy response in
      cancer patients.

PMID- 23161839
TI  - Slow ethics for nursing practice.

PMID- 23161838
TI  - Cytologic findings of acute leukemia in bronchoalveolar lavage fluid.
AB  - Bronchoalveolar lavage (BAL) is often performed in patients with acute leukemia
      developed with respiratory failure or pulmonary infiltrates. Patients usually
      undergo BAL to rule out infection. Occasionally, however, leukemic infiltrate may
      be detected. We present a series of 11 cases in which the diagnosis of leukemia
      was made on the BAL material. We retrospectively reviewed all BAL samples from
      January 1, 2006 to December 31, 2008. There were a total of 1,130 cases, of which
      139 showed malignant cytology, including 10 with leukemia. Sixteen samples were
      unsatisfactory and 904 were benign, of which 32 had identifiable microorganisms.
      In additional to the 10 leukemia cases identified, two more were reviewed after
      the search criteria. The 12 patients (seven men, five women) ranged from 22 to 75
      years old. All patients had previously biopsy-proven leukemia [two acute
      myelomonocytic leukemia, two acute promyelocytic leukemia, two acute myeloid
      leukemia (AML) with inv16, two therapy-related AML, one acute monocytic leukemia,
      one chronic myeloid leukemia in blast face, one AML with maturation, one
      myelodysplastic syndrome with excess blasts, and one large granular leukemia].
      Four had a prior diagnosis of myelodysplastic syndrome. The time from initial
      diagnosis of leukemia to BAL ranged from 1 to 233 days, with 8 of 10 occurring
      within 8 days of diagnosis. Symptoms that prompted BAL included shortness of
      breath/hypoxia (8), fever (3), chest pain (2), and cough (2). Chest X-rays in all
      cases revealed opacities or consolidations mimicking an inflammatory process.
      Seven patients subsequently died, while three were alive, and, in remission, and
      two were lost to follow-up. The presence of a leukemic infiltrate can mimic
      infection. BAL is a relatively safe and useful diagnostic tool in this setting
      for differentiating a leukemic infiltrate from an infection/inflammatory
      infiltrate. The prognosis of patients with lung involvement of acute leukemia is
      poor.

PMID- 23161840
TI  - Are nurses inherently unfit to manage fitness to practice?

PMID- 23161842
TI  - Online monitoring of intelligent polymers for drug release with hyperpolarized
      xenon.
AB  - Welcome to the guest zone: By combining hyperpolarized xenon and simple low-field
      NMR devices it is possible to obtain more control over hydrogels that show
      potential as drug delivery systems. An alternative way of polymer swelling-degree
      determination is demonstrated with real-time NMR analysis. An ideal region for
      solvent uptake can be defined in which the absorbed solvent molecules are
      completely confined in the nano-porous network of the hydrogel.

PMID- 23161843
TI  - Self-assembly and colloidal polymerization of polymer-nanoparticle hybrids into
      mesoscopic chains.
AB  - No, it's not frogspawn! Polymer-coated gold nanoparticles can be assembled into
      extended mesoscopic chains with precise dimensional control. Here, the conditions
      can be adjusted to promote the fusion of polymeric ligands into cylindrical
      micellar aggregates. This type of colloidal polymerization offers a new and
      versatile route to a variety of mesoscopic assemblies of nanoparticles.

PMID- 23161844
TI  - Combining quantum mechanical ligand conformation analysis and protein modeling to
      elucidate GPCR-ligand binding modes.
AB  - SAR beyond protein-ligand interactions: By combining structure-affinity
      relationships, protein-ligand modeling studies, and quantum mechanical
      calculations, we show that ligand conformational energies and basicity play
      critical roles in ligand binding to the histamine H4 receptor, a GPCR that plays
      a key role in inflammation.

PMID- 23161845
TI  - Synthesis of fivefold stellate polyhedral gold nanoparticles with {110}-facets
      via a seed-mediated growth method.
AB  - New Type of Gold Nanoparticle: A new class of fivefold stellate polyhedral gold
      nanoparticles (FSPAuNPs) with {110} facets have been synthesized by a seed
      mediated growth method without adding surfactant. The size of FSPAuNPs can be
      simply adjusted from nanoscale to microscale by varying the amount of seeds,
      which results in a shift of the surface plasmon resonance peak from the visible
      to the NIR range.

PMID- 23161846
TI  - Chiral copper(II)-catalyzed enantioselective boron conjugate additions to
      alpha,beta-unsaturated carbonyl compounds in water.

PMID- 23161847
TI  - Innovative approach using an intragastric balloon for weight loss in a morbidly
      obese patient undergoing liver transplantation.

PMID- 23161848
TI  - "Raspberry bodies," extracellular hyaline globules and branching hyaline stromal
      fragments in a fine-needle aspirate of metastatic clear cell carcinoma of the
      ovary.

PMID- 23161849
TI  - Response to: Statistical analysis of missense mutation classifiers.

PMID- 23161850
TI  - Revealing the subtle interplay of thermal and quantum fluctuation effects on
      contact ion pairing in microsolvated HCl.
AB  - The combined effect of thermal fluctuations and quantum mechanical motion on the
      HCl(H2O)4 cluster is studied at different temperatures. Two conformations of this
      cluster are investigated: the ringlike structure that involves an undissociated
      HCl molecule (UD) and the contact ion pair (CIP), which involves the dissociated
      acid, Cl(-), and H3O(+). The UD structure is affected by thermal and quantum
      fluctuations in a similar way. The hydrogen-bond network is destabilized, and
      this results in ring expansion and proton orientational rearrangements, though
      the thermal excitation prevails over the quantum effects at high temperature,
      while the zero-point motion dominates in the low-temperature regime, as expected.
      In contrast, the thermal and quantum fluctuations exert competing effects on the
      CIP structure. At high temperature one of the hydrogen bonds accepted by Cl(-)
      breaks, and this results in undercoordination of the Cl site, which leads to
      proton transfer along the fluxional Cl(-)...H3O(+) hydrogen bond and formation of
      molecular HCl. Thus, thermal fluctuations counteract acid dissociation and thus
      ion-pair formation. At low temperature however, the decreasing thermal
      excitations facilitate recovery of the full hydrogen-bond network, which pushes
      the proton away from the Cl site and thus leads to acid dissociation, which
      characterizes the equilibrium structure. On the other hand, quantum mechanical
      fluctuations, which destabilize the hydrogen bonds supporting the Cl(-) ion and
      pull the proton back towards the undissociated limit, become of overriding
      importance in the low-temperature limit. As a result, the subtle balance between
      the two trends enables temperature-dependent "low-barrier hydrogen bonding" and
      establishes a centered hydrogen bond, H2O...H(+)...Cl(-), at intermediate
      temperatures.

PMID- 23161851
TI  - Association between plasma cyclic guanosine monophosphate levels and hemodynamic
      instability during liver transplantation.
AB  - The activation of cyclic guanosine monophosphate (cGMP) production in patients
      with end-stage liver disease (ESLD) has been associated with hemodynamic
      instability during orthotopic liver transplantation (OLT). The aim of this
      prospective, observational study was to investigate the involvement of cGMP in
      the mediation of profound hypotension during liver graft reperfusion. An
      additional objective was to determine whether preoperative cGMP levels are
      associated with intraoperative hemodynamic instability. Forty-four consecutive
      patients undergoing OLT were included in the study. Blood samples for cGMP
      analysis were obtained from (1) the radial artery before the surgical incision;
      (2) the radial artery, portal vein, and flush blood during the anhepatic phase;
      and (3) the radial artery 20 minutes after liver graft reperfusion. On the basis
      of a statistical analysis, the patients were divided into 2 groups: group 1
      (preoperative cGMP level >= 0.05 MUmol/L) and group 2 (preoperative cGMP level <
      0.05 MUmol/L). We demonstrated a significant correlation between the preoperative
      levels of cGMP and the amount of catecholamine required to maintain hemodynamic
      stability during reperfusion (r = 0.52, P < 0.001), the length of the hospital
      stay (r = 0.38, P = 0.01), and the length of the intensive care unit (ICU) stay
      (r = 0.44, P = 0.004). We also demonstrated a significantly higher intraoperative
      catecholamine requirement (P < 0.001) and a prolonged postoperative ICU stay (P =
      0.02) in group 1 patients versus group 2 patients. In conclusion, this study
      demonstrates increased baseline cGMP production in patients with ESLD, which is
      significantly associated with severe hypotension during OLT. We suggest that
      preoperative levels of cGMP correlate with hemodynamic instability during liver
      graft reperfusion.

PMID- 23161852
TI  - Analysis of BRCA1 variants in double-strand break repair by homologous
      recombination and single-strand annealing.
AB  - Missense substitutions of uncertain clinical significance in the BRCA1 gene are a
      vexing problem in genetic counseling for women who have a family history of
      breast cancer. In this study, we evaluated the functions of 29 missense
      substitutions of BRCA1 in two DNA repair pathways. Repair of double-strand breaks
      by homology-directed recombination (HDR) had been previously analyzed for 16 of
      these BRCA1 variants, and 13 more variants were analyzed in this study. All 29
      variants were also analyzed for function in double-strand break repair by the
      single-strand annealing (SSA) pathway. We found that among the pathogenic
      mutations in BRCA1, all were defective for DNA repair by either pathway. The HDR
      assay was accurate because all pathogenic mutants were defective for HDR, and all
      nonpathogenic variants were fully functional for HDR. Repair by SSA accurately
      identified pathogenic mutants, but several nonpathogenic variants were scored as
      defective or partially defective. These results indicated that specific amino
      acid residues of the BRCA1 protein have different effects in the two related DNA
      repair pathways, and these results validate the HDR assay as highly correlative
      with BRCA1-associated breast cancer.

PMID- 23161853
TI  - Overexpression of OsRecQl4 and/or OsExo1 enhances DSB-induced homologous
      recombination in rice.
AB  - During homologous recombination (HR)-mediated DNA double-strand break (DSB)
      repair in eukaryotes, an initial step is the creation of a 3'-single-stranded DNA
      (ssDNA) overhang via resection of a 5' end. Rad51 polymerizes on this ssDNA to
      search for a homologous sequence, and the gapped sequence is then repaired using
      an undamaged homologous DNA strand as template. Recent studies in eukaryotes
      indicate that resection of the DSB site is promoted by the cooperative action of
      RecQ helicase family proteins: Bloom helicase (BLM) in mammals or Sgs1 in yeast,
      and exonuclease 1 (Exo1). However, the role of RecQ helicase and exonuclease
      during the 5'-resection process of HR in plant cells has not yet been defined.
      Here, we demonstrate that overexpression of rice proteins OsRecQl4 (BLM
      counterpart) and/or OsExo1 (Exo1 homolog) can enhance DSB processing, as
      evaluated by recombination substrate reporter lines in rice. These results could
      be applied to construct an efficient gene targeting system in rice.

PMID- 23161854
TI  - The K+-dependent asparaginase, NSE1, is crucial for plant growth and seed
      production in Lotus japonicus.
AB  - The physiological role of K(+)-dependent and K(+)-independent asparaginases in
      plants remains unclear, and the contribution from individual isoforms during
      development is poorly understood. We have used reverse genetics to assess the
      phenotypes produced by the deficiency of K(+)-dependent NSE1 asparaginase in the
      model legume Lotus japonicus. For this purpose, four different mutants were
      identified by TILLING and characterized, two of which affected the structure and
      function of the asparaginase molecule and caused asparagine accumulation. Plant
      growth and total seed weight of mature mutant seeds as well as the level of both
      legumin and convicilin seed storage proteins were affected in the mutants. The
      mutants isolated in the present work are the first of their type in legumes and
      have enabled us to demonstrate the importance of asparagine and K(+)-dependent
      NSE1 asparaginase for nitrogen remobilization and seed production in L. japonicus
      plants.

PMID- 23161855
TI  - Evolution of Bradyrhizobium-Aeschynomene mutualism: living testimony of the
      ancient world or highly evolved state?
AB  - Until recently it had been well established that the initial step in legume
      rhizobia symbioses was flavonoid and Nod factor (NF) signaling. However, NF
      independent symbiosis is now known to occur between Bradyrhizobium and some
      species of Aeschynomene. Since its discovery, this unusual symbiotic system has
      attracted attention, and efforts have been devoted to revealing the NF
      independent symbiotic mechanism, although the molecular mechanisms of nodule
      initiation still remain to be elucidated. NF-independent symbiosis is also
      interesting from the perspective of the evolution of legume-rhizobia symbiosis.
      In this mini-review, we discuss the current literature on the NF-independent
      symbiotic system in terms of phylogeny of the partners, infection, bacteroid
      differentiation, nodule structure, photosynthesis, endophytic features and model
      host plant. We also discuss NF-independent symbiosis, which is generally regarded
      to be more primitive than NF-dependent symbiosis, because the bacteria invade
      host plants via 'crack entry'. We propose three possible scenarios concerning the
      evolution of NF-independent symbiosis, which do not exclude the possibility that
      the NF-independent system evolved from NF-dependent interactions. Finally, we
      examine an interesting question on Bradyrhizobium-Aeschynomene mutualism, which
      is how do they initiate symbiosis without NF. Phylogenetic and genomic analyses
      of symbiotic and non-symbiotic bradyrhizobia with A. indica may be crucial to
      address the question, because of the very narrow phylogeny of natural
      endosymbionts without nod genes compared with other legume-rhizobia symbioses.

PMID- 23161856
TI  - Overexpression of a wheat aquaporin gene, TaAQP8, enhances salt stress tolerance
      in transgenic tobacco.
AB  - Aquaporin (AQP) proteins have been shown to transport water and other small
      molecules through biological membranes, which is crucial for plants to combat
      salt stress. However, the precise role of AQP genes in salt stress response is
      not completely understood in plants. In this study, a PIP1 subgroup AQP gene,
      designated TaAQP8, was cloned and characterized from wheat. Transient expression
      of TaAQP8-green fluorescent protein (GFP) fusion protein revealed its
      localization in the plasma membrane. TaAQP8 exhibited water channel activity in
      Xenopus laevis oocytes. TaAQP8 transcript was induced by NaCl, ethylene and
      H(2)O(2). Further investigation showed that up-regulation of TaAQP8 under salt
      stress involves ethylene and H(2)O(2) signaling, with ethylene causing a positive
      effect and H(2)O(2) acting as a negative factor. Overexpression of TaAQP8 in
      tobacco increased root elongation compared with controls under salt stress. The
      roots of transgenic plants also retained a high K(+)/Na(+) ratio and Ca(2+)
      content, but reduced H(2)O(2) accumulation by an enhancement of superoxide
      dismutase (SOD), catalase (CAT) and peroxidase (POD) activities under salt
      stress. Further investigation showed that whole seedlings from transgenic lines
      displayed higher SOD, CAT and POD activities, increased NtSOD and NtCAT
      transcript levels, and decreased H(2)O(2) accumulation and membrane injury under
      salt stress. Taken together, our results demonstrate that TaAQP8 confers salt
      stress tolerance not only by retaining high a K(+)/Na(+) ratio and Ca(2+)
      content, but also by reducing H(2)O(2) accumulation and membrane damage by
      enhancing the antioxidant system.

PMID- 23161857
TI  - Reference genes for high-throughput quantitative reverse transcription-PCR
      analysis of gene expression in organs and tissues of Eucalyptus grown in various
      environmental conditions.
AB  - Interest in the genomics of Eucalyptus has skyrocketed thanks to the recent
      sequencing of the genome of Eucalyptus grandis and to a growing number of large
      scale transcriptomic studies. Quantitative reverse transcription-PCR (RT-PCR) is
      the method of choice for gene expression analysis and can now also be used as a
      high-throughput method. The selection of appropriate internal controls is
      becoming of utmost importance to ensure accurate expression results in
      Eucalyptus. To this end, we selected 21 candidate reference genes and used high
      throughput microfluidic dynamic arrays to assess their expression among a large
      panel of developmental and environmental conditions with a special focus on wood
      forming tissues. We analyzed the expression stability of these genes by using
      three distinct statistical algorithms (geNorm, NormFinder and DeltaCt), and used
      principal component analysis to compare methods and rankings. We showed that the
      most stable genes identified depended not only on the panel of biological samples
      considered but also on the statistical method used. We then developed a
      comprehensive integration of the rankings generated by the three methods and
      identified the optimal reference genes for 17 distinct experimental sets covering
      13 organs and tissues, as well as various developmental and environmental
      conditions. The expression patterns of Eucalyptus master genes EgMYB1 and EgMYB2
      experimentally validated our selection. Our findings provide an important
      resource for the selection of appropriate reference genes for accurate and
      reliable normalization of gene expression data in the organs and tissues of
      Eucalyptus trees grown in a range of conditions including abiotic stresses.

PMID- 23161858
TI  - PGR5-dependent cyclic electron transport around PSI contributes to the redox
      homeostasis in chloroplasts rather than CO(2) fixation and biomass production in
      rice.
AB  - The PGR5 (PROTON GRADIENT REGULATION 5) gene that is required for PSI cyclic
      electron transport in Arabidopsis was knocked down in rice (Oryza sativa). In
      three PGR5 knockdown (KD) lines, the PGR5 protein level was reduced to 5-8% of
      that in the wild type, resulting in a 50% reduction in PGRL1 (PGR5-LIKE
      PHOTOSYNTHETIC PHENOTYPE 1) protein levels. In ruptured chloroplasts, ferredoxin
      dependent plastoquinone reduction activity was partially impaired; the phenotype
      was mimicked by addition of antimycin A to wild-type chloroplasts. As occurred in
      the Arabidopsis pgr5 mutant, non-photochemical quenching of Chl fluorescence
      (NPQ) induction was impaired in the leaves, but the electron transport rate (ETR)
      was only mildly affected at high light intensity. The P700(+) level was reduced
      even at low light intensity, suggesting that the PGR5 function was severely
      disturbed as in the Arabidopsis pgr5 mutant and that the other alternative routes
      of electrons could not compensate the stromal redox balance. The amplitude of the
      light-dark electrochromic shift (ECS) signal (ECSt), which reflects the total
      size of the proton motive force in steady-state photosynthesis, was reduced by 13
      25% at approximately the growth light intensity. The CO(2) fixation rate was only
      slightly reduced in the PGR5 KD lines. Despite the drastic reduction in NPQ and
      P700(+) levels, total biomass was only slightly reduced in PGR5 KD lines grown at
      370 umol photons m(-2) s(-1). These results suggest that CO(2) fixation and
      growth rate are very robust in the face of alterations in the fundamental
      reactions of photosynthesis under constant light conditions in rice.

PMID- 23161859
TI  - Both phototropin 1 and 2 localize on the chloroplast outer membrane with distinct
      localization activity.
AB  - Chloroplasts change their position to adapt cellular activities to fluctuating
      environmental light conditions. Phototropins (phot1 and phot2 in Arabidopsis) are
      plant-specific blue light photoreceptors that perceive changes in light intensity
      and direction, and mediate actin-based chloroplast photorelocation movements.
      Both phot1 and phot2 regulate the chloroplast accumulation response, while phot2
      is mostly responsible for the regulation of the avoidance response. Although it
      has been widely accepted that distinct intracellular localizations of
      phototropins are implicated in the specificity, the mechanism underlying the
      phot2-specific avoidance response has remained elusive. In this study, we
      examined the relationship of the phot2 localization pattern to the chloroplast
      photorelocation movement. First, the fusion of a nuclear localization signal with
      phot2, which effectively reduced the amount of phot2 in the cytoplasm, retained
      the activity for both the accumulation and avoidance responses, indicating that
      membrane-localized phot2 but not cytoplasmic phot2 is functional to mediate the
      responses. Importantly, some fractions of phot2, and of phot1 to a lesser extent,
      were localized on the chloroplast outer membrane. Moreover, the deletion of the C
      terminal region of phot2, which was previously shown to be defective in blue
      light-induced Golgi localization and avoidance response, affected the
      localization pattern on the chloroplast outer membrane. Taken together, these
      results suggest that dynamic phot2 trafficking from the plasma membrane to the
      Golgi apparatus and the chloroplast outer membrane might be involved in the
      avoidance response.

PMID- 23161860
TI  - Academic research in medicine: the need for teamwork and leadership.

PMID- 23161861
TI  - Alkali-metal azides interacting with metal-organic frameworks.
AB  - Interactions between alkali-metal azides and metal-organic framework (MOF)
      derivatives, namely, the first and third members of the isoreticular MOF (IRMOF)
      family, IRMOF-1 and IRMOF-3, are studied within the density functional theory
      (DFT) paradigm. The investigations take into account different models of the
      selected IRMOFs. The mutual influence between the alkali-metal azides and the pi
      rings or Zn centers of the involved MOF derivatives are studied by considering
      the interactions both of the alkali-metal cations with model aromatic centers and
      of the alkali-metal azides with distinct sites of differently sized models of
      IRMOF-1 and IRMOF-3. Several exchange and correlation functionals are employed to
      calculate the corresponding interaction energies. Remarkably, it is found that,
      with increasing alkali-metal atom size, the latter decrease for cations
      interacting with the pi-ring systems and increase for the azides interacting with
      the MOF fragments. The opposite behavior is explained by stabilization effects on
      the azide moieties and determined by the Zn atoms, which constitute the inorganic
      vertices of the IRMOF species. Larger cations can, in fact, coordinate more
      efficiently to both the aromatic center and the azide anion, and thus stabilizing
      bridging arrangements of the azide between one alkali-metal and two Zn atoms in
      an eta(2) coordination mode are more favored.

PMID- 23161862
TI  - Sustainable synthesis of diverse privileged heterocycles by palladium-catalyzed
      aerobic oxidative isocyanide insertion.
AB  - O(2) in, H(2)O out: Various diamines and related bisnucleophiles readily undergo
      oxidative isocyanide insertion with Pd(OAc)(2) (1 mol %) as the catalyst and O(2)
      as the terminal oxidant to give a diverse array of medicinally relevant N
      heterocycles. The utility of this highly sustainable method is demonstrated by a
      formal synthesis of the antihistamines astemizole and norastemizole.

PMID- 23161863
TI  - Efficient electroluminescence from excimers of 1,3,6,8-tetrakis(3,5
      dimethylphenyl)pyrene.
AB  - Excimers are generally considered as detrimental to OLEDs. For pyrene-based
      chromophores, however, this is not always true. In this contribution, two new
      methylated tetraphenylpyrenes, 1,3,6,8-tetra-o-tolylpyrene (TTPy) and 1,3,6,8
      tetrakis(3,5-dimethylphenyl)pyrene (TDMPPy), were synthesized through Suzuki
      coupling reactions. TDMPPy absorbs and emits light at longer wavelengths than
      TTPy due to its more planar conformation and thus better conjugation. TDMPPy is
      prone to excimer formation, thus leading to a strong bathochromic shift (84 nm)
      in the photoluminescence spectrum of its film. TDMPPy exhibits efficient
      electroluminescence originating from pyrene excimers, affording a maximum
      luminance of 26,670 cd m(-2) and a current efficiency as high as 10.8 cd A(-1) in
      a non-doped OLED (ITO/PEDOT:PSS (50 nm)/NPB (30 nm)/TDMPPy (30 nm)/TPBI (40
      nm)/Ca:Ag).

PMID- 23161864
TI  - Motor representations in the intact hemisphere of the rat are reduced after
      repetitive training of the impaired forelimb.
AB  - BACKGROUND: During recovery from a unilateral cortical stroke, spared cortical
      motor areas in the contralateral (intact) cerebral cortex are recruited.
      Preclinical studies have demonstrated that compensation with the less-impaired
      limb may have a detrimental inhibitory effect on the intact cortical hemisphere
      and could impede recovery of the more-impaired limb. However, evidence from
      detailed neurophysiological mapping studies in animal models is lacking.
      OBJECTIVES: The present study examines neurophysiological changes in the intact
      hemisphere of the rat following a unilateral ischemic infarct to cortical
      forelimb motor areas. METHODS: A total of 8 rats were trained for 2 weeks on a
      reach and retrieval task prior to an ischemic infarct induced by the
      vasoconstrictor endothelin-1 injected into the cortical gray matter encompassing
      the 2 forelimb motor representations: the caudal forelimb area (CFA) and the
      rostral forelimb area (RFA). Animals were randomly assigned to an
      infarct/training group (n = 4) or an infarct/no-training group (ie, spontaneous
      recovery, n = 4). After a 5-week postinfarct period, motor areas of the intact
      hemisphere (CFA and RFA) were characterized using intracortical microstimulation
      techniques. The resulting maps of evoked movements were compared with maps
      derived from CFA and RFA in normal rats (normal, n = 5; normal/training, n = 4).
      RESULTS: Compared with the normal/no-training group, CFA representations were
      significantly smaller in the infarct/training group but not in the infarct/no
      training group. No significant differences were found in RFA. CONCLUSIONS:
      Repetitive training of the more-impaired forelimb during the postinfarct recovery
      period reduces the size of motor representations in the intact hemisphere.

PMID- 23161865
TI  - The effects of an aerobic and resistance exercise training program on cognition
      following stroke.
AB  - BACKGROUND: Cognitive benefits obtained from exercise in healthy populations
      support the idea that aerobic and resistance training (AT+RT) would confer
      benefit for poststroke recovery. However, there is little evidence regarding the
      effectiveness of such programs. OBJECTIVE: To evaluate the effects of a 6-month
      exercise program of AT+RT on cognition in consecutively enrolled patients with
      motor impairments >=10 weeks poststroke. METHODS: Outcomes were measured before
      and after 6 months of AT+RT on 41 patients. Cognition was measured by the
      Montreal Cognitive Assessment (MoCA). Secondary measures included evaluation of
      gas exchange anaerobic threshold (ATge), body composition by dual energy X-ray
      absorptiometry, and depressive symptoms by questionnaire. RESULTS: There were
      significant improvements in overall MoCA scores (22.5 +/- 4.5 to 24.0 +/- 3.9, P
      < .001) as well as in the subdomains of attention/concentration (4.7 +/- 1.7 to
      5.2 +/- 1.3, P = .03) and visuospatial/executive function (3.4 +/- 1.1 to 3.9 +/-
      1.1, P = .002). There was a significant reduction in the proportion of patients
      meeting the threshold criteria for mild cognitive impairment (MCI) at baseline
      compared with posttraining (65.9% vs 36.6%, P < .001). In a linear regression
      model, there was a positive association between change in cognitive function and
      change in fat-free mass of the nonaffected limbs (beta = .002; P = .005) and
      change in attention/concentration and change in ATge (beta = .383; P <= .001),
      independent of age, sex, time from stroke, and change in fat mass and depression
      score. CONCLUSION: A combined training model (AT+RT) resulted in improvements in
      cognitive function and a reduction in the proportion of patients meeting the
      threshold criteria for MCI. Change in cognition was positively associated with
      change in fat-free mass and ATge.

PMID- 23161866
TI  - Effects of mutated pregnancy-associated plasma protein-a on atherosclerotic
      lesion development in mice.
AB  - Pregnancy-associated plasma protein-A (PAPP-A) is a large multidomain
      metalloprotease involved in cleavage of IGF binding protein (IGFBP)-4 and -5
      thereby causing release of bioactive IGF. Individual domains of PAPP-A have been
      characterized in vitro, including the metzincin proteolytic domain important for
      IGFBP proteolytic activity, short consensus repeats critical for cell surface
      association, and Lin-12/Notch repeat module demonstrated to determine IGFBP
      substrate specificity. To test the hypothesis that specific cleavage of IGFBP-4
      by PAPP-A in close proximity to the cell surface is required for development of
      lesions in a murine model of atherosclerosis, the following PAPP-A transgenic
      (Tg) mice were generated: Tg(E483A), which lacks all PAPP-A proteolytic activity;
      Tg(D1499A), which selectively lacks proteolytic activity against IGFBP-4; and
      Tg(K1296A/K1316A), in which cell surface binding is compromised. Following cross
      breeding with apolipoprotein E (ApoE) knockout (KO) mice, ApoE KO/Tg mice were
      fed a high-fat diet to promote aortic lesion development. Lesion area was
      increased 2-fold in aortas from ApoE KO/Tg wild-type compared with ApoE KO mice
      (P < 0.001). However, there was no significant increase in the lesion area in any
      of the ApoE KO/Tg mutant mice. We conclude that PAPP-A proteolytic activity is
      required for the lesion-promoting effect of PAPP-A and that its specificity must
      be directed against IGFBP-4. Furthermore, our data demonstrate that cleavage of
      IGFBP-4 at a distance from the cell surface, and hence from the IGF receptor, is
      not effective in promoting the development of the atherosclerotic lesions. Thus,
      PAPP-A exerts its effect while bound to the cell surface in vivo.

PMID- 23161867
TI  - IL-15 overexpression promotes endurance, oxidative energy metabolism, and muscle
      PPARdelta, SIRT1, PGC-1alpha, and PGC-1beta expression in male mice.
AB  - Endurance exercise initiates a pattern of gene expression that promotes fat
      oxidation, which in turn improves endurance, body composition, and insulin
      sensitivity. The signals from exercise that initiate these pathways have not been
      completely characterized. IL-15 is a cytokine that is up-regulated in skeletal
      muscle after exercise and correlates with leanness and insulin sensitivity. To
      determine whether IL-15 can induce any of the metabolic adaptations associated
      with exercise, substrate metabolism, endurance, and molecular expression patterns
      were examined in male transgenic mice with constitutively elevated muscle and
      circulating IL-15 levels. IL-15 transgenic mice ran twice as long as littermate
      control mice in a run-to-exhaustion trial and preferentially used fat for energy
      metabolism. Fast muscles in IL-15 transgenic mice exhibited high expression of
      intracellular mediators of oxidative metabolism that are induced by exercise,
      including sirtuin 1, peroxisome proliferator-activated receptor (PPAR)-delta,
      PPAR-gamma coactivator-1alpha, and PPAR-gamma coactivator-1beta. Muscle tissue in
      IL-15 transgenic mice exhibited myosin heavy chain and troponin I mRNA isoform
      expression patterns indicative of a more oxidative phenotype than controls. These
      findings support a role for IL-15 in induction of exercise endurance, oxidative
      metabolism, and skeletal muscle molecular adaptations induced by physical
      training.

PMID- 23161868
TI  - Ras-dva is a novel Pit-1- and glucocorticoid-regulated gene in the embryonic
      anterior pituitary gland.
AB  - Glucocorticoids play a role in functional differentiation of pituitary
      somatotrophs and lactotrophs during embryogenesis. Ras-dva was identified as a
      gene regulated by anterior neural fold protein-1/homeobox expressed in embryonic
      stem cells-1, a transcription factor known to be critical in pituitary
      development, and has an expression profile in the chicken embryonic pituitary
      gland that is consistent with in vivo regulation by glucocorticoids. The
      objective of this study was to characterize expression and regulation of ras-dva
      mRNA in the developing chicken anterior pituitary. Pituitary ras-dva mRNA levels
      increased during embryogenesis to a maximum on embryonic day (e) 18 and then
      decreased and remained low or undetectable after hatch. Ras-dva expression was
      highly enriched in the pituitary gland on e18 relative to other tissues examined.
      Glucocorticoid treatment of pituitary cells from mid- and late-stage embryos
      rapidly increased ras-dva mRNA, suggesting it may be a direct transcriptional
      target of glucocorticoids. A reporter construct driven by 4 kb of the chicken ras
      dva 5'-flanking region, containing six putative pituitary-specific transcription
      factor-1 (Pit-1) binding sites and two potential glucocorticoid receptor (GR)
      binding sites, was highly activated in embryonic pituitary cells and up-regulated
      by corticosterone. Mutagenesis of the most proximal Pit-1 site decreased promoter
      activity in chicken e11 pituitary cells, indicating regulation of ras-dva by Pit
      1. However, mutating putative GR binding sites did not substantially reduce
      induction of ras-dva promoter activity by corticosterone, suggesting additional
      DNA elements within the 5'-flanking region are responsible for glucocorticoid
      regulation. We have identified ras-dva as a glucocorticoid-regulated gene that is
      likely expressed in cells of the Pit-1 lineage within the developing anterior
      pituitary gland.

PMID- 23161869
TI  - AgRP innervation onto POMC neurons increases with age and is accelerated with
      chronic high-fat feeding in male mice.
AB  - In many mammals, body weight increases continuously throughout adulthood until
      late middle age. The hormone leptin is necessary for maintaining body weight, in
      that high levels of leptin promote negative energy balance. As animals age,
      however, their increase in body weight is accompanied by a steady rise in
      circulating leptin levels, indicating the progressive development of
      counterregulatory mechanisms to antagonize leptin's anorexigenic effects.
      Hypothalamic neurons coexpressing agouti-related peptide (AgRP) and neuropeptide
      Y are direct leptin targets. These neurons promote positive energy balance, and
      they inhibit anorexigenic proopiomelanocortin (POMC) neurons via direct
      neuropeptide action and release of gamma-aminobutyric acid. We show here that
      AgRP and neuropeptide Y innvervation onto POMC neurons increases dramatically
      with age in male mice. This is associated with progressive increase of inhibitory
      postsynaptic currents and decrease of POMC firing rate with age. Neuronal
      activity is significantly attenuated in POMC neurons that receive a high density
      of AgRP puncta. These high-density AgRP inputs correlate with leptin levels in
      normal mice and are nearly absent in mice lacking leptin. The progression of
      increased AgRP innervation onto POMC somas is accelerated in hyperleptinemic,
      diet-induced obese mice. Together our study suggests that modulation of
      hypothalamic AgRP innervation constitutes one mechanism to counter the effects of
      the age-associated rise in leptin levels, thus sustaining body weight and fat
      mass at an elevated level in adulthood.

PMID- 23161870
TI  - Characterization, neurosteroid binding and brain distribution of human membrane
      progesterone receptors delta and {epsilon} (mPRdelta and mPR{epsilon}) and
      mPRdelta involvement in neurosteroid inhibition of apoptosis.
AB  - Three members of the progestin and adipoQ receptor (PAQR) family, PAQR-7, PAQR-8,
      and PAQR-5 [membrane progesterone (P4) receptor (PR) (mPR)alpha, mPRbeta, and
      mPRgamma], function as plasma mPRs coupled to G proteins in mammalian cells, but
      the characteristics of two other members, PAQR6 and PAQR9 (mPRdelta and
      mPRepsilon), remain unclear, because they have only been investigated in yeast
      expression systems. Here, we show that recombinant human mPRdelta and mPRepsilon
      expressed in MDA-MB-231 breast cancer cells display specific, saturable, high
      affinity [(3)H]-P4 binding on the plasma membranes of transfected cells with
      equilibrium dissociation constants (K(d)s) of 2.71 and 2.85 nm, respectively, and
      low affinity for R5020, characteristics typical of mPRs. P4 treatment increased
      cAMP production as well as [(35)S]-guanosine 5'-triphosphate (GTP)gammaS binding
      to transfected cell membranes, which was immunoprecipitated with a stimulatory G
      protein antibody, suggesting both mPRdelta and mPRepsilon activate a stimulatory
      G protein (Gs), unlike other mPRs, which activate an inhibitory G protein (Gi).
      All five mPR mRNAs were detected in different regions of the human brain, but
      mPRdelta showed greatest expression in many regions, including the forebrain,
      hypothalamus, amygdala, corpus callosum, and spinal cord, whereas mPRepsilon was
      abundant in the pituitary gland and hypothalamus. Allopregnanolone and other
      neurosteroids bound to mPRdelta and other mPRs and acted as agonists, activating
      second messengers and decreased starvation-induced cell death and apoptosis in
      mPRdelta-transfected cells and in hippocampal neuronal cells at low nanomolar
      concentrations. The results suggest that mPRdelta and mPRepsilon function as mPRs
      coupled to G proteins and are potential intermediaries of nonclassical
      antiapoptotic actions of neurosteroids in the central nervous system.

PMID- 23161871
TI  - Cerebellar abnormalities in mice lacking type 3 deiodinase and partial reversal
      of phenotype by deletion of thyroid hormone receptor alpha1.
AB  - Thyroid hormone serves many functions throughout brain development, but the
      mechanisms that control the timing of its actions in specific brain regions are
      poorly understood. In the cerebellum, thyroid hormone controls formation of the
      transient external germinal layer, which contains proliferative granule cell
      precursors, subsequent granule cell migration, and cerebellar foliation. We
      report that the thyroid hormone-inactivating type 3 deiodinase (encoded by Dio3)
      is expressed in the mouse cerebellum at embryonic and neonatal stages, suggesting
      a need to protect cerebellar tissues from premature stimulation by thyroid
      hormone. Dio3(-/-) mice displayed reduced foliation, accelerated disappearance of
      the external germinal layer, and premature expansion of the molecular layer at
      juvenile ages. Furthermore, Dio3(-/-) mice exhibited locomotor behavioral
      abnormalities and impaired ability in descending a vertical pole. To ascertain
      that these phenotypes resulted from inappropriate exposure to thyroid hormone,
      thyroid hormone receptor alpha1 (TRalpha1) was removed from Dio3(-/-) mice, which
      substantially corrected the cerebellar and behavioral phenotypes. Deletion of
      TRalpha1 did not correct the previously reported small thyroid gland or deafness
      in Dio3(-/-) mice, indicating that Dio3 controls the activation of specific
      receptor isoforms in different tissues. These findings suggest that type 3
      deiodinase constrains the timing of thyroid hormone action during cerebellar
      development.

PMID- 23161872
TI  - Multiple cholinergic signaling pathways in pituitary gonadotrophs.
AB  - Acetylcholine (ACh) has been established as a paracrine factor in the anterior
      pituitary gland, but the receptors mediating ACh action and the cell types
      bearing these receptors have not been identified. Our results showed that the
      expression of the nicotinic subunits mRNAs followed the order beta2 > beta1 =
      alpha9 > alpha4 in cultured rat pituitary cells. The expression of the subunits
      in immortalized LbetaT2 mouse gonadotrophs followed the order beta2 > alpha4 =
      alpha1. M4 > M3 muscarinic receptor mRNA were also identified in pituitary and
      LbetaT2 cells. The treatment of cultured pituitary cells with GnRH down-regulated
      the expression of alpha9 and alpha4 mRNAs, without affecting the expression of M3
      and M4 receptor mRNAs, and ACh did not alter the expression of GnRH receptor
      mRNA. We also performed double immunostaining to show the expression of beta2
      subunit and M4 receptor proteins in gonadotrophs. Functional nicotinic channels
      capable of generating an inward current, facilitation of electrical activity, and
      Ca(2+) influx were identified in single gonadotrophs and LbetaT2 cells. In both
      cell types, the M3 receptor-mediated, phospholipase C-dependent Ca(2+)
      mobilization activated an outward apamin-sensitive K(+) current and caused
      hyperpolarization. The activation of M4 receptors by ACh inhibited cAMP
      production and GnRH-induced LH release in a pertussis toxin-sensitive manner. We
      concluded that multiple cholinergic receptors are expressed in gonadotrophs and
      that the main secretory action of ACh is inhibitory through M4 receptor-mediated
      down-regulation of cAMP production. The expression of nicotinic receptors in
      vitro compensates for the lack of regular GnRH stimulation of gonadotrophs.

PMID- 23161874
TI  - Ultra-small, uniform, and single bcc-phased Fe(x)Co(1-x)/graphitic shell
      nanocrystals for T1 magnetic resonance imaging contrast agents.
AB  - We have synthesized ultra-small and uniform Fe(x)Co(1-x)/graphitic carbon shell
      (Fe(x)Co(1-x)/GC) nanocrystals (x=0.13, 0.36, 0.42, 0.50, 0.56, and 0.62,
      respectively) with average diameters of <4 nm by thermal decomposition of metal
      precursors in approximately 60 nm MCM-41 and methane CVD. The composition of the
      Fe(x)Co(1-x)/GC nanocrystals can be tuned by changing the Fe:Co ratios of the
      metal precursors. The Fe(x)Co(1-x)/GC nanocrystals show superparamagnetic
      properties at room temperature. The Fe(0.50)Co(0.50)/GC, Fe(0.56)Co(0.44)/GC, and
      Fe(0.62)Co(0.38)/GC nanocrystals have a single bcc FeCo structure, whereas the
      Fe(0.13)Co(0.87)/GC, Fe(0.36)Co(0.64)/GC, and Fe(0.42)Co(0.58)/GC nanocrystals
      have a mixed structure of bcc FeCo and fcc Co. The single bcc-phased Fe(x)Co(1
      x)/GC nanocrystals functionalized with phospholipid-poly(ethylene glycol) (PL
      PEG) in phosphate buffered saline (PBS) are demonstrated to be excellent T(1) MRI
      contrast agents.

PMID- 23161873
TI  - The role of the carbohydrate response element-binding protein in male fructose
      fed rats.
AB  - By 2030, nearly half of Americans will have nonalcoholic fatty liver disease. In
      part, this epidemic is fueled by the increasing consumption of caloric sweeteners
      coupled with an innate capacity to convert sugar into fat via hepatic de novo
      lipogenesis. In addition to serving as substrates, monosaccharides also increase
      the expression of key enzymes involved in de novo lipogenesis via the
      carbohydrate response element-binding protein (ChREBP). To determine whether
      ChREBP is a potential therapeutic target, we decreased hepatic expression of
      ChREBP with a specific antisense oligonucleotide (ASO) in male Sprague-Dawley
      rats fed either a high-fructose or high-fat diet. ChREBP ASO treatment decreased
      plasma triglyceride concentrations compared with control ASO treatment in both
      diet groups. The reduction was more pronounced in the fructose-fed group and
      attributed to decreased hepatic expression of ACC2, FAS, SCD1, and MTTP and a
      decrease in the rate of hepatic triglyceride secretion. This was associated with
      an increase in insulin-stimulated peripheral glucose uptake, as assessed by the
      hyperinsulinemic-euglycemic clamp. In contrast, ChREBP ASO did not alter hepatic
      lipid content or hepatic insulin sensitivity. Interestingly, fructose-fed rats
      treated with ChREBP ASO had increased plasma uric acid, alanine transaminase, and
      aspartate aminotransferase concentrations. This was associated with decreased
      expression of fructose aldolase and fructokinase, reminiscent of inherited
      disorders of fructose metabolism. In summary, these studies suggest that
      targeting ChREBP may prevent fructose-induced hypertriglyceridemia but without
      the improvements in hepatic steatosis and hepatic insulin responsiveness.

PMID- 23161875
TI  - Paronychia induced by the epidermal growth factor receptor inhibitor cetuximab.
AB  - While the development of epidermal growth factor receptor inhibitors has been
      hailed as a remarkable triumph in the field of oncology, it has inherited with it
      a host of cutaneous side-effects that have been increasingly observed in a
      substantial number of patients in the recent years. One cutaneous manifestation
      that may inflict significant pain and affect activities of daily living among
      some of the patients receiving epidermal growth factor receptor inhibitors is
      paronychia. A case of paronychia associated with the use of cetuximab in the
      management of KRAS wild-type midrectal adenocarcinoma along with its management
      has been described. 

PMID- 23161876
TI  - Impact of foliar symptoms of "Esca proper" on proteins related to defense and
      oxidative stress of grape skins during ripening.
AB  - Esca is one of the major diseases affecting vineyards with direct impact on
      product yield; nevertheless, scientific studies concerning its impact on grape
      quality are scarce. As an attempt to better understand the mechanisms behind
      "Esca proper" development in grapes, this work focused on the identification of
      proteins whose expression is altered by the disease. 2-DEs were performed on
      protein extracts from grape skins at different stages of maturity for two
      consecutive vintages. Grapes were collected in 2009 and in 2010 from plants that
      did not present signs of infection by Esca proper since the 2004 vintage and from
      plants that presented cast leaf symptoms at least once since 2004. For the first
      time, 13 proteins were shown to be influenced by Esca proper during the ripening
      process. Extensive bioinformatics analysis allowed the grouping of proteins
      involved in (i) stress tolerance and defense response, (ii) oxidative
      phosphorylation, (iii) oxidation-reduction processes in mitochondria, and (iv)
      oxidation-reduction processes in chloroplasts. Of these 13 proteins, cysteine
      synthase is the only one implicated in a metabolic pathway of oenological
      interest. This study shows how foliar symptoms of Esca proper may impact stress
      related pathways in grapes, which are characterized by modifications in the chain
      of oxidative phosphorylation and redox scavenging.

PMID- 23161877
TI  - Streptozotocin-induced diabetes differentially affects sympathetic innervation
      and control of plantar metatarsal and mesenteric arteries in the rat.
AB  - In humans neural control of arterial vessels supplying skin in the extremities is
      particularly vulnerable to the effects of diabetes. Here the streptozotocin (STZ)
      rat model of type 1 diabetes was used to compare effects on neurovascular
      function in plantar metatarsal arteries (PMAs), which supply blood to skin of
      hind paw digits, with those in mesenteric arteries (MAs). Twelve weeks after STZ
      (60 mg/kg ip), wire myography was used to assess vascular function. In PMAs,
      lumen dimensions were unchanged but both nerve-evoked contractions and
      sensitivity to alpha(1) (phenylephrine, methoxamine)- and alpha(2) (clonidine)
      adrenoceptor agonists were reduced. The density of perivascular nerve fibers was
      also reduced by ~25%. These changes were not observed in PMAs from STZ-treated
      rats receiving either a low dose of insulin that did not greatly reduce blood
      glucose levels or a high dose of insulin that markedly reduced blood glucose
      levels. In MAs from STZ-treated rats, nerve-evoked increases in force did not
      differ from control but, because lumen dimensions were ~20% larger, nerve-evoked
      increases in effective transmural pressure were smaller. Increases in effective
      transmural pressure produced by phenylephrine or alpha,beta-methylene ATP in MAs
      from STZ-treated rats were not smaller than control, but the density of
      perivascular nerve fibers was reduced by ~10%. In MAs, the increase in vascular
      dimensions is primarily responsible for reducing effectiveness of nerve-evoked
      constrictions. By contrast, in PMAs decreases in both the density of perivascular
      nerve fibers and the reactivity of the vascular muscle appear to explain
      impairment of neurovascular transmission.

PMID- 23161878
TI  - Effects of intrathecal kynurenate on arterial pressure during chronic osmotic
      stress in conscious rats.
AB  - Increased plasma osmolality elevates mean arterial pressure (MAP) through
      activation of the sympathetic nervous system, but the neurotransmitters released
      in the spinal cord to regulate MAP during osmotic stress remain unresolved.
      Glutamatergic neurons of the rostral ventrolateral medulla project to sympathetic
      preganglionic neurons in the spinal cord and are likely activated during
      conditions of osmotic stress; however, this has not been examined in conscious
      rats. This study investigated whether increased MAP during chronic osmotic stress
      depends on activation of spinal glutamate receptors. Rats were chronically
      instrumented with an indwelling intrathecal (i.t.) catheter for antagonist
      delivery to the spinal cord and a radiotelemetry transmitter for continuous
      monitoring of MAP and heart rate. Osmotic stress induced by 48 h of water
      deprivation (WD) increased MAP by ~15 mmHg. Intrathecal kynurenic acid, a
      nonspecific antagonist of ionotropic glutamate receptors, decreased MAP
      significantly more after 48 h of WD compared with the water-replete state. Water
      deprived rats also showed a greater fall in MAP in response to i.t. 2-amino-5
      phosphonovalerate. Finally, i.t. kynurenic acid also decreased MAP more in an
      osmotically driven model of neurogenic hypertension, the DOCA-salt rat, compared
      with normotensive controls. Our results suggest that spinally released glutamate
      mediates increased MAP during 48-h WD and DOCA-salt hypertension.

PMID- 23161879
TI  - Cardiomyocyte-specific overexpression of an active form of Rac predisposes the
      heart to increased myocardial stunning and ischemia-reperfusion injury.
AB  - The GTP-binding protein Rac regulates diverse cellular functions including
      activation of NADPH oxidase, a major source of superoxide production (O(2)(.-)).
      Rac1-mediated NADPH oxidase activation is increased after myocardial infarction
      (MI) and heart failure both in animals and humans; however, the impact of
      increased myocardial Rac on impending ischemia-reperfusion (I/R) is unknown. A
      novel transgenic mouse model with cardiac-specific overexpression of
      constitutively active mutant form of Zea maize Rac D (ZmRacD) gene has been
      reported with increased myocardial Rac-GTPase activity and O(2)(.-) generation.
      The goal of the present study was to determine signaling pathways related to
      increased myocardial ZmRacD and to what extent hearts with increased ZmRacD
      proteins are susceptible to I/R injury. The effect of myocardial I/R was examined
      in young adult wild-type (WT) and ZmRacD transgenic (TG) mice. In vitro
      reversible myocardial I/R for postischemic cardiac function and in vivo regional
      myocardial I/R for MI were performed. Following 20-min global ischemia and 45-min
      reperfusion, postischemic cardiac contractile function and heart rate were
      significantly reduced in TG hearts compared with WT hearts. Importantly, acute
      regional myocardial I/R (30-min ischemia and 24-h reperfusion) caused
      significantly larger MI in TG mice compared with WT mice. Western blot analysis
      of cardiac homogenates revealed that increased myocardial ZmRacD gene expression
      is associated with concomitant increased levels of NADPH oxidase subunit
      gp91(phox), O(2)(.-), and P(21)-activated kinase. Thus these findings provide
      direct evidence that increased levels of active myocardial Rac renders the heart
      susceptible to increased postischemic contractile dysfunction and MI following
      acute I/R.

PMID- 23161880
TI  - The Anrep effect: 100 years later.
AB  - Myocardial stretch elicits a rapid increase in developed force, which is mainly
      caused by an increase in myofilament calcium sensitivity (Frank-Starling
      mechanism). Over the ensuing 10-15 min, a second gradual increase in force takes
      place. This slow force response to stretch is known to be the result of an
      increase in the calcium transient amplitude and constitutes the in vitro
      equivalent of the Anrep effect described 100 years ago in the intact heart. In
      the present review, we will update and discuss what is known about the Anrep
      effect as the mechanical counterpart of autocrine/paracrine mechanisms involved
      in its genesis. The chain of events triggered by myocardial stretch comprises 1)
      release of angiotensin II, 2) release of endothelin, 3) activation of the
      mineralocorticoid receptor, 4) transactivation of the epidermal growth factor
      receptor, 5) increased formation of mitochondria reactive oxygen species, 6)
      activation of redox-sensitive kinases upstream myocardial Na(+)/H(+) exchanger
      (NHE1), 7) NHE1 activation, 8) increase in intracellular Na(+) concentration, and
      9) increase in Ca(2+) transient amplitude through the Na(+)/Ca(2+) exchanger. We
      will present the experimental evidence supporting each of the signaling steps
      leading to the Anrep effect and its blunting by silencing NHE1 expression with a
      specific small hairpin interference RNA injected into the ventricular wall.

PMID- 23161882
TI  - Gender disparities in scholarly productivity within academic otolaryngology
      departments.
AB  - OBJECTIVE: To examine whether there are gender disparities in scholarly
      productivity within academic otolaryngology departments, as measured by academic
      rank and the h-index, a published, objective measure of research contributions
      that quantifies the number and significance of papers published by a given
      author. STUDY DESIGN AND SETTING: Analysis of bibliometric data of academic
      otolaryngologists. METHODS: Faculty listings from academic otolaryngology
      departments were used to determine academic rank and gender. The Scopus database
      was used to determine h-index and publication range (in years) of these faculty
      members. In addition, 20 randomly chosen institutions were used to compare
      academic otolaryngologists to faculty members in other surgical specialties.
      RESULTS: Mean h-indices increased through the rank of professor. Among academic
      otolaryngologists, men had significantly higher h-indices than women, a finding
      also noted on examination of faculty members from other specialties. Men had
      higher research productivity rates at earlier points in their career than women
      did. The productivity rates of women increased and equaled or surpassed those of
      men later in their careers. Men had higher absolute h-index values at junior
      academic ranks. Women academic otolaryngologists of senior rank had higher
      absolute h-indices than their male counterparts. CONCLUSIONS: The h-index
      measures research significance in an objective manner and indicates that although
      men have higher overall research productivity in academic otolaryngology, women
      demonstrate a different productivity curve. Women produce less research output
      earlier in their careers than men do, but at senior levels, they equal or exceed
      the research productivity of men.

PMID- 23161881
TI  - Cardiomyocyte architectural plasticity in fetal, neonatal, and adult pig hearts
      delineated with diffusion tensor MRI.
AB  - Cardiomyocyte organization is a critical determinant of coordinated cardiac
      contractile function. Because of the acute opening of the pulmonary circulation,
      the relative workload of the left ventricle (LV) and right ventricle (RV) changes
      substantially immediately after birth. We hypothesized that three-dimensional
      cardiomyocyte architecture might be required to adapt rapidly to accommodate
      programmed perinatal changes of cardiac function. Isolated fixed hearts from pig
      fetuses or pigs at midgestation, preborn, postnatal day 1 (P1), postnatal day 5,
      postnatal day 14 (P14), and adulthood (n = 5 for each group) were acquired for
      diffusion-weighted magnetic resonance imaging. Cardiomyocyte architecture was
      visualized by three-dimensional fiber tracking and was quantitatively evaluated
      by the measured helix angle (alpha(h)). Upon the completion of MRI, hearts were
      sectioned and stained with hematoxylin/eosin (H&E) to evaluate cardiomyocyte
      alignment, with picrosirius red to evaluate collagen content, and with anti-Ki67
      to evaluate postnatal cell proliferation. The helical architecture of
      cardiomyocyte was observed as early as the midgestational period. Postnatal
      changes of cardiomyocyte architecture were observed from P1 to P14, which primary
      occurred in the septum and RV free wall (RVFW). In the septum, the volume ratio
      of LV- vs. RV-associated cardiomyocytes rapidly changed from RV-LV balanced
      pattern at birth to LV dominant pattern by P14. In the RVFW, subendocardial
      alpha(h) decreased by ~30 degrees  from P1 to P14. These findings indicate that
      the helical architecture of cardiomyocyte is developed as early as the
      midgestation period. Substantial and rapid adaptive changes in cardiac
      microarchitecture suggested considerable developmental plasticity of
      cardiomyocyte form and function in the postnatal period in response to altered
      cardiac mechanical function.

PMID- 23161883
TI  - Mentorship in otolaryngology: 10 years of experience.

PMID- 23161884
TI  - TGF-beta-Smad3 signaling in emphysema and pulmonary fibrosis: an epigenetic
      aberration of normal development?
AB  - It is well accepted that TGF-beta signaling has critical functional roles in lung
      development, injury, and repair. We showed previously that null mutation of
      Smad3, a critical node in the TGF-beta pathway, protects mice against fibrosis
      induced by bleomycin. However, more recently we noticed that abnormal
      alveolarization also occurs in Smad3-deficient mice and that this is followed by
      progressive emphysema-like alveolar wall destruction mediated by MMP9. We now
      know that Smad3 cooperates with c-Jun to synergistically regulate a protein
      deacetylase SIRT1, by binding to an AP-1 site in the SIRT1 promoter.
      Consistently, Smad3 knockout lung at postnatal day 28 had reduced SIRT1
      expression, which in turn resulted in increased histone acetylation at the
      binding sites of the transcription factors AP-1, NF-kappaB, and Pea3 on the MMP9
      promoter, as well as increased acetylation of NF-kappaB. Thus, upon TGF-beta
      activation, phosphorylated Smad3 can be translocated into the nucleus with Smad4,
      whereat Smad3 in turn collaborates with c-Jun to activate SIRT1 transcription.
      SIRT1 can deacetylate NF-kappaB at lysine 30, as well as histones adjacent to the
      transcription factor AP-1, NF-kappaB, and Pea3 binding sites of the MMP9
      promoter, thereby suppressing MMP9 transcription, hence fixing MMP9 in the OFF
      mode. Conversely, when Smad3 is missing, this regulatory pathway is inactivated
      so that MMP9 is epigenetically turned ON. We postulate that these developmental
      epigenetic mechanisms by which Smad3 regulates MMP9 transcription cell
      autonomously may be important in modulating both emphysema and pulmonary fibrosis
      and that this could explain why both pathologies can appear within the same lung
      specimen.

PMID- 23161885
TI  - Automated measurement of blood flow velocity and direction and hemoglobin oxygen
      saturation in the rat lung using intravital microscopy.
AB  - Intravital microscopy of the pulmonary microcirculation in research animals is of
      great scientific interest for its utility in identifying regional changes in
      pulmonary microcirculatory blood flow. Although feasibility studies have been
      reported, the pulmonary window can be further refined into a practical tool for
      pharmaceutical research and drug development. We have established a method to
      visualize and quantify dynamic changes in three key features of lung function:
      microvascular red blood cell velocity, flow direction, and hemoglobin saturation.
      These physiological parameters were measured in an acute closed-chest pulmonary
      window, which allows real-time images to be captured by fluorescence and
      multispectral absorption microscopy; images were subsequently quantified using
      computerized analysis. We validated the model by quantifying changes in
      microcirculatory blood flow and hemoglobin saturation in two ways: 1) after
      changes in inspired oxygen content and 2) after pharmacological reduction of
      pulmonary blood flow via treatment with the beta1 adrenergic receptor blocker
      metoprolol. This robust and relatively simple system facilitates pulmonary
      intravital microscopy in laboratory rats for pharmacological and physiological
      research.

PMID- 23161886
TI  - ADAM15 deficiency attenuates pulmonary hyperpermeability and acute lung injury in
      lipopolysaccharide-treated mice.
AB  - ADAM15 is a disintegrin and metalloprotease recently implicated in cancer and
      chronic immune disorders. We have recently characterized ADAM15 as a mediator of
      endothelial barrier dysfunction. Whether this molecule contributes to acute
      inflammation has not been evaluated. The purpose of this study was to investigate
      the role of ADAM15 in mediating pulmonary microvascular leakage during acute
      inflammatory injury. Immunofluorescent staining and Western blotting revealed
      that the endothelium was the main source of ADAM15 in lung tissue. In a mouse
      model of acute lung injury induced by lipopolysaccharide (LPS), upregulation of
      ADAM15 was observed in association with pulmonary edema and neutrophil
      infiltration. The LPS-induced inflammatory injury, as demonstrated by
      bronchoalveolar lavage neutrophil count, lung wet-to-dry weight ratio, and
      myeloperoxidase activity, was significantly attenuated in Adam15(-/-) mice.
      Studies with primary cell culture demonstrated abundant ADAM15 expression in
      endothelial cells (ECs) of mouse lung but not in neutrophils. Deficiency of
      ADAM15 in ECs had no obvious effect on basal permeability but significantly
      attenuated hyperpermeability response to LPS as evidenced by albumin flux assay
      and measurements of transendothelial electrical resistance, respectively. ADAM15
      deficiency also reduced neutrophil chemotactic transmigration across endothelial
      barriers in the presence or absence of formyl-methionyl-leucyl-phenylalanine
      (fMLP). Rescue expression of ADAM15 in Adam15(-/-) ECs restored neutrophil
      transendothelial migration. These data indicate that ADAM15 upregulation
      contributes to inflammatory lung injury by promoting endothelial
      hyperpermeability and neutrophil transmigration.

PMID- 23161887
TI  - A galactoglycerolipid lipase is required for triacylglycerol accumulation and
      survival following nitrogen deprivation in Chlamydomonas reinhardtii.
AB  - Following N deprivation, microalgae accumulate triacylglycerols (TAGs). To gain
      mechanistic insights into this phenomenon, we identified mutants with reduced TAG
      content following N deprivation in the model alga Chlamydomonas reinhardtii. In
      one of the mutants, the disruption of a galactoglycerolipid lipase-encoding gene,
      designated PLASTID GALACTOGLYCEROLIPID DEGRADATION1 (PGD1), was responsible for
      the primary phenotype: reduced TAG content, altered TAG composition, and reduced
      galactoglycerolipid turnover. The recombinant PGD1 protein, which was purified
      from Escherichia coli extracts, hydrolyzed monogalactosyldiacylglycerol into its
      lyso-lipid derivative. In vivo pulse-chase labeling identified
      galactoglycerolipid pools as a major source of fatty acids esterified in TAGs
      following N deprivation. Moreover, the fatty acid flux from plastid lipids to TAG
      was decreased in the pgd1 mutant. Apparently, de novo-synthesized fatty acids in
      Chlamydomonas reinhardtii are, at least partially, first incorporated into
      plastid lipids before they enter TAG synthesis. As a secondary effect, the pgd1
      mutant exhibited a loss of viability following N deprivation, which could be
      avoided by blocking photosynthetic electron transport. Thus, the pgd1 mutant
      provides evidence for an important biological function of TAG synthesis following
      N deprivation, namely, relieving a detrimental overreduction of the
      photosynthetic electron transport chain.

PMID- 23161888
TI  - A triantagonistic basic helix-loop-helix system regulates cell elongation in
      Arabidopsis.
AB  - In plants, basic helix-loop-helix (bHLH) transcription factors play important
      roles in the control of cell elongation. Two bHLH proteins, PACLOBTRAZOL
      RESISTANCE1 (PRE1) and Arabidopsis ILI1 binding bHLH1 (IBH1), antagonistically
      regulate cell elongation in response to brassinosteroid and gibberellin
      signaling, but the detailed molecular mechanisms by which these factors regulate
      cell elongation remain unclear. Here, we identify the bHLH transcriptional
      activators for cell elongation (ACEs) and demonstrate that PRE1, IBH1, and the
      ACEs constitute a triantagonistic bHLH system that competitively regulates cell
      elongation. In this system, the ACE bHLH transcription factors directly activate
      the expression of enzyme genes for cell elongation by interacting with their
      promoter regions. IBH1 negatively regulates cell elongation by interacting with
      the ACEs and thus interfering with their DNA binding. PRE1 interacts with IBH1
      and counteracts the ability of IBH1 to affect ACEs. Therefore, PRE1 restores the
      transcriptional activity of ACEs, resulting in induction of cell elongation. The
      balance of triantagonistic bHLH proteins, ACEs, IBH1, and PRE1, might be
      important for determination of the size of plant cells. The expression of IBH1
      and PRE1 is regulated by brassinosteroid, gibberellins, and developmental phase
      dependent factors, indicating that two phytohormones and phase-dependent signals
      are integrated by this triantagonistic bHLH system.

PMID- 23161890
TI  - Sleep evaluation by actigraphy for drinkers.

PMID- 23161889
TI  - The requirement for carotenoids in the assembly and function of the
      photosynthetic complexes in Chlamydomonas reinhardtii.
AB  - We have investigated the importance of carotenoids on the accumulation and
      function of the photosynthetic apparatus using a mutant of the green alga
      Chlamydomonas reinhardtii lacking carotenoids. The FN68 mutant is deficient in
      phytoene synthase, the first enzyme of the carotenoid biosynthesis pathway, and
      therefore is unable to synthesize any carotenes and xanthophylls. We find that
      FN68 is unable to accumulate the light-harvesting complexes associated with both
      photosystems as well as the RC subunits of photosystem II. The accumulation of
      the cytochrome b6f complex is also strongly reduced to a level approximately 10%
      that of the wild type. However, the residual fraction of assembled cytochrome b6f
      complexes exhibits single-turnover electron transfer kinetics comparable to those
      observed in the wild-type strain. Surprisingly, photosystem I is assembled to
      significant levels in the absence of carotenoids in FN68 and possesses functional
      properties that are very similar to those of the wild-type complex.

PMID- 23161891
TI  - Mothers with alcoholic liver disease and the risk for preterm and small-for
      gestational-age birth.
AB  - AIMS: To study pregnancy outcome in women with alcoholic liver disease (ALD).
      METHODS: Using the Swedish nation-wide Patient and Medical Birth Registers, we
      investigated risk of adverse pregnancy outcome in 720 women diagnosed with ALD
      before and 1720 diagnosed after birth and compared them with 24 460 population
      based control births. RESULTS: Women with ALD diagnosed before or after birth
      were generally of higher age and body mass index, more likely to smoke cigarettes
      during pregnancy and to have a low socio-economic status compared with controls.
      Women diagnosed with ALD before birth had an increased risk of moderately and
      very preterm birth, adjusted odd ratio (OR) = 1.53 (95% confidence interval (CI):
      1.37-1.72 and 1.15-2.06 95%), respectively. Infants of mothers with ALD before
      birth were more often small-for-gestational age, adjusted OR = 1.22 (95% CI: 1.05
      1.43), and were at increased risk for low Apgar scores (<7) at 5 min, adjusted OR
      = 1.49 (95% CI: 1.15-1.92) compared with controls. Similar associations with
      slightly lower-risk estimates were found among women diagnosed with ALD after
      birth. CONCLUSIONS: ALD is associated with adverse-birth outcomes, highlighting
      the importance of screening women for alcohol dependence in antenatal care.

PMID- 23161892
TI  - Supplementary thiamine is still important in alcohol dependence.
AB  - AIMS: To assess the effect of mandatory thiamine enrichment of wheat flour on
      blood thiamine levels in an alcohol-dependent population. METHODS: Alcohol
      dependent clients (n = 100) entering an inpatient service for the management of
      alcohol withdrawal had thiamine blood tests and diet interviews. Approximately
      half (n = 46) the alcohol-dependent participants reported taking vitamin
      supplements prior to admission. Standard treatment included thiamine
      supplementation in the form of an intramuscular injection and 100 mg tablets. If
      consent was gained, a second thiamine blood test was taken prior to discharge (n
      = 77). Control participants (n = 20) with no history of treatment for alcohol
      abuse had thiamine blood tests and diet interviews. RESULTS: Control participants
      consumed significantly larger amounts of thiamine in their diet compared with
      alcohol-dependent participants (P < 0.0001). Alcohol-dependent participants who
      reported no use of vitamin supplements had significantly lower (P < 0.05) blood
      thiamine levels compared with controls, whereas controls and those who reported
      using vitamin supplements had no significant difference. No significant
      correlation was found between thiamine blood levels and reported levels of
      alcohol consumption. CONCLUSION: Reduced blood levels of thiamine in people who
      are alcohol dependent, compared with those with no history of alcohol abuse, are
      likely to be because of the poor diet. Consumption of vitamin supplements appears
      to bring thiamine levels closer to those seen in control participants.
      Supplementation of dietary intake of thiamine in people who are alcohol dependent
      remains an important measure for the prevention of Wernicke-Korsakoff's syndrome
      in this population.

PMID- 23161893
TI  - Acceptability and effect of a community-based alcohol education program in rural
      Sri Lanka.
AB  - AIMS: To assess the effectiveness and acceptability of a brief community-based
      educational program on changing the drinking pattern of alcohol in a rural
      community. METHODS: A longitudinal cohort study was carried out in two rural
      villages in Sri Lanka. One randomly selected village received a community
      education program that utilized street dramas, poster campaigns, leaflets and
      individual and group discussions. The control village had no intervention during
      this period. The Alcohol Use Disorder Identification Test (AUDIT) was used to
      measure the drinking pattern before and at 6 and 24 months after the intervention
      in males over 18 years of age in both villages. The recall and the impact of
      various components of the intervention were assessed at 24 months post
      intervention. RESULTS: The intervention was associated with the development of an
      active community action group in the village and a significant reduction in
      illicit alcohol outlets. The drama component of the intervention had the highest
      level of recall and preference. Comparing the control and intervention villages,
      there were no significant difference between baseline drinking patterns and the
      AUDIT. There was a significant reduction in the AUDIT scores in the intervention
      village compared with the control at 6 and 24 months (P < 0.0001). CONCLUSIONS: A
      community-based education program had high acceptance and produces a reduction in
      alcohol use that was sustained for 2 years.

PMID- 23161894
TI  - Comparative analysis of pharmacovigilance methods in the detection of adverse
      drug reactions using electronic medical records.
AB  - OBJECTIVE: Medication  safety requires that each drug be monitored throughout its
      market life as early detection of adverse drug reactions (ADRs) can lead to
      alerts that prevent patient harm. Recently, electronic medical records (EMRs)
      have emerged as a valuable resource for pharmacovigilance. This study examines
      the use of retrospective medication orders and inpatient laboratory results
      documented in the EMR to identify ADRs. METHODS: Using 12 years of EMR data from
      Vanderbilt University Medical Center (VUMC), we designed a study to correlate
      abnormal laboratory results with specific drug administrations by comparing the
      outcomes of a drug-exposed group and a matched unexposed group. We assessed the
      relative merits of six pharmacovigilance measures used in spontaneous reporting
      systems (SRSs): proportional reporting ratio (PRR), reporting OR (ROR), Yule's Q
      (YULE), the chi(2) test (CHI), Bayesian confidence propagation neural networks
      (BCPNN), and a gamma Poisson shrinker (GPS). RESULTS: We systematically evaluated
      the methods on two independently constructed reference standard datasets of drug
      event pairs. The dataset of Yoon et al contained 470 drug-event pairs (10 drugs
      and 47 laboratory abnormalities). Using VUMC's EMR, we created another dataset of
      378 drug-event pairs (nine drugs and 42 laboratory abnormalities). Evaluation on
      our reference standard showed that CHI, ROR, PRR, and YULE all had the same F
      score (62%). When the reference standard of Yoon et al was used, ROR had the best
      F score of 68%, with 77% precision and 61% recall. CONCLUSIONS: Results suggest
      that EMR-derived laboratory measurements and medication orders can help to
      validate previously reported ADRs, and detect new ADRs.

PMID- 23161895
TI  - Adherence to drug-drug interaction alerts in high-risk patients: a trial of
      context-enhanced alerting.
AB  - OBJECTIVE: Drug-drug interaction (DDI) alerting is an important form of clinical
      decision support, yet physicians often fail to attend to critical DDI warnings
      due to alert fatigue. We previously described a model for highlighting patients
      at high risk of a DDI by enhancing alerts with relevant laboratory data. We
      sought to evaluate the effect of this model on alert adherence in high-risk
      patients. METHODS: A 6-month randomized controlled trial involving 1029
      outpatient physicians was performed. The target interactions were all DDIs known
      to cause hyperkalemia. Alerts in the intervention group were enhanced with the
      patient's most recent potassium and creatinine levels. The control group received
      unmodified alerts. High -risk patients were those with baseline potassium >5.0
      mEq/l and/or creatinine >=1.5 mg/dl (132 MUmol/l). RESULTS: We found no
      significant difference in alert adherence in high-risk patients between the
      intervention group (15.3%) and the control group (16.8%) (p=0.71). Adherence in
      normal risk patients was significantly lower in the intervention group (14.6%)
      than in the control group (18.6%) (p<0.01). In neither group did physicians
      increase adherence in patients at high risk. CONCLUSIONS: Physicians adhere
      poorly to hyperkalemia-associated DDI alerts even in patients with risk factors
      for a clinically significant interaction, and the display of relevant laboratory
      data in these alerts did not improve adherence levels in the outpatient setting.
      Further research is necessary to determine optimal strategies for conveying
      patient-specific DDI risk.

PMID- 23161896
TI  - Re: "prenatal exposure to mercury and infant neurodevelopment in a multicenter
      cohort in Spain: study of potential modifiers".

PMID- 23161898
TI  - Randomized phase 2 trial on refinement of early-stage NSCLC adjuvant chemotherapy
      with cisplatin and pemetrexed versus cisplatin and vinorelbine: the TREAT study.
AB  - BACKGROUND: Adjuvant chemotherapy is beneficial in non-small-cell lung cancer
      (NSCLC). However, balancing toxicity and efficacy mandates improvement. PATIENTS
      AND METHODS: Patients with completely resected stages IB-pT3N1 NSCLC were
      randomly assigned to either four cycles cisplatin (C: 50 mg/m(2) day (d)1 + 8)
      and vinorelbine (V: 25 mg/m(2) d1, 8, 15, 22) q4 weeks or four cycles cisplatin
      (75 mg/m(2) d1) and pemetrexed (Px: 500 mg/m(2) d1) q3 weeks. Primary objective
      was the clinical feasibility rate (no grade (G)4 neutropenia/thrombocytopenia or
      thrombocytopenia with bleeding, no G3/4 febrile neutropenia or non-hematological
      toxicity; no premature withdrawal/death). Secondary objectives were drug delivery
      and efficacy. RESULTS: One hundred and thirty two patients were randomized
      (stages: 38% IB, 10% IIA, 47% IIB, 5% pT3pN1; histology: 43% squamous, 57% non
      squamous). The feasibility rates were 95.5% (cisplatin and pemetrexed, CPx) and
      75.4% (cisplatin and vinorelbine, CVb) (P = 0.001); hematological G3/4 toxic
      effects were 10% (CPx) and 74% (CVb) (P < 0.001), non-hematological toxic effects
      were comparable (33% and 31%, P = 0.798). Delivery of total mean doses was 90% of
      planned with CPx, but 66% (cisplatin) and 64% (vinorelbine) with CVb (P <
      0.0001). The median number of cycles [treatment time (weeks)] was 4 for CPx
      (11.2) and 3 for CVb (9.9). Time to withdrawal from therapy differed
      significantly between arms favoring CPx (P < 0.001). CONCLUSION: Adjuvant
      chemotherapy with CPx is safe and feasible with less toxicity and superior dose
      delivery compared with CVb.

PMID- 23161897
TI  - African ancestry and genetic risk for uterine leiomyomata.
AB  - Rates of uterine leiomyomata (UL) are 2-3 times higher in African Americans than
      in European Americans. It is unclear whether inherited factors explain the ethnic
      disparity. To investigate the presence of risk alleles for UL that are highly
      differentiated in frequency between African Americans and European Americans, the
      authors conducted an admixture-based genome-wide scan of 2,453 UL cases confirmed
      by ultrasound or surgery in the Black Women's Health Study (1997-2009), a
      national prospective cohort study. Controls (n = 2,102) were women who did not
      report a UL diagnosis through 2009. Mean percentage of European ancestry was
      significantly lower among cases (20.00%) than among controls (21.63%; age
      adjusted mean difference = -1.76%, 95% confidence interval: -2.40, -1.12; P <
      0.0001), and the association was stronger in younger cases. Admixture analyses
      showed suggestive evidence of association at chromosomes 2, 4, and 10. The
      authors also genotyped a dense set of tag single nucleotide polymorphisms at
      different loci associated with UL in Japanese women but failed to replicate the
      associations. This suggests that genetic variation for UL differs in populations
      with and without African ancestry. The admixture findings further indicate that
      no single highly differentiated locus is responsible for the ethnic disparity in
      UL, raising the possibility that multiple variants jointly contribute to the
      higher incidence of UL in African Americans.

PMID- 23161899
TI  - Oral administration of GLPG0259, an inhibitor of MAPKAPK5, a new target for the
      treatment of rheumatoid arthritis: a phase II, randomised, double-blind, placebo
      controlled, multicentre trial.
AB  - BACKGROUND: Mitogen-activated protein (MAP) kinases are key regulators of
      cytokine production, and are therefore potential targets for treatment of
      rheumatoid arthritis (RA). OBJECTIVE: This two-part phase II study investigated
      the efficacy and safety of a once-daily 50 mg GLPG0259 (an inhibitor of MAP
      kinase-activated protein kinase 5) dose vs placebo (part A). An interim analysis
      after part A would determine whether the dose-finding part (part B) would be
      performed. METHODS: In part A, eligible methotrexate (MTX)-refractory patients
      with RA were randomised to receive either a once-daily 50 mg dose of GLPG0259 or
      placebo, in addition to a stable dose of MTX, for 12 weeks. The primary efficacy
      end point was the percentage of patients achieving an American College of
      Rheumatology 20% improvement (ACR20) response after 12 weeks. RESULTS: The
      interim analysis showed no difference between the percentage of subjects
      achieving the primary efficacy variable of ACR20 or the secondary efficacy
      variables (ACR50, ACR70 and Disease Activity Score 28) at week 12 in the GLPG0259
      treated (n=19) and placebo-treated (n=11) groups. Owing to lack of efficacy, the
      study was terminated, and part B was not initiated. CONCLUSIONS: This innovative
      study design quickly provided conclusive results on the lack of efficacy of
      GLPG0259 in patients with RA.

PMID- 23161901
TI  - Methotrexate polyglutamation in relation to infliximab pharmacokinetics in
      rheumatoid arthritis.
AB  - OBJECTIVE: The combination of methotrexate (MTX) with infliximab can modify
      infliximab pharmacokinetics and lower the incidence of antibodies against
      infliximab (ATIs). We hypothesised that the pharmacokinetic interaction between
      MTX and infliximab is related to activation of MTX to immunosuppressive MTX
      polyglutamates (MTXPGs). METHODS: Adult patients with rheumatoid arthritis
      receiving weekly MTX with infliximab for more than 3 months were enrolled in a
      cross-sectional study. Blood was collected at trough before the infusion of
      infliximab. Red blood cell (RBC) MTXPGs were measured using liquid
      chromatography, and circulating levels of infliximab were measured using a cell
      based assay. ATIs were measured using enzyme immunoassays. Statistical analyses
      consisted of multiple regression and Wilcoxon tests. RESULTS: In the 61 patients
      enrolled in the study, ATIs were detected in 11 (18%). Regression analyses
      revealed that lower infliximab levels (median 3.3 ug/ml) were associated with the
      presence of ATIs and lower RBC MTXPG levels (median 28 nmol/l) (p<0.05). Logistic
      regression revealed that RBC MTXPG levels above 25 nmol/l were associated with a
      4.7-fold lower likelihood of having ATIs (OR=4.7; 95% CI 1.1 to 20.8; p=0.02).
      None of the 12 patients with RBC MTXPG levels above 50 nmol/l tested positive for
      ATIs. CONCLUSIONS: These hypothesis-generating data indicate that MTXPGs are
      associated with infliximab pharmacokinetics and ATI formation.

PMID- 23161900
TI  - Notch signalling pathways mediate synovial angiogenesis in response to vascular
      endothelial growth factor and angiopoietin 2.
AB  - OBJECTIVE: Notch signalling pathways are critical for angiogenesis and
      endothelial cell (EC) fate; however the mechanisms regulating these processes in
      the inflamed joint remain to be elucidated. Here, we examine whether Notch
      signalling mediates vascular endothelial growth factor (VEGF) and angiopoietin 2
      (Ang2)-induced vascular function. METHODS: Notch-1 intracellular domain (Notch-1
      IC), Notch-4 IC, Delta-like-ligand 4, Hes-related transcriptional repressors-1
      and 2 (Hrt-1, Hrt-2) mRNA and/or protein expression was measured by Real-time PCR
      and/or western blot. VEGF/Ang2 induced EC function was assessed using transwell
      invasion chambers, matrigel tube formation assays and wound repair scratch
      assays+/-Notch-1 siRNA or an gamma-secretase inhibitor N-(N-(3,5
      Difluorophenacetyl-L-alanly))-S-phenylglycine-t-Butyl Ester (DAPT) in RA synovial
      explants or human microvascular EC. Interleukin (IL)-6 and IL-8 were measured by
      ELISA and MMP2 and 9 by gelatine zymography. RESULTS: Notch-1 IC and Notch-4 IC
      protein expressions were demonstrated in RA and psoriatic arthritis synovial
      biopsies, with minimal expression observed in Osteoarthritis (OA). VEGF and Ang2
      induced Notch-1 IC/ Notch-4 IC protein expression in synovial explant cultures
      and human microvascular EC levels were further potentiated by VEGF/Ang2
      stimulation in combination. Notch-1, Delta-like-ligand 4, and Hrt-2 mRNA
      expression were significantly induced by VEGF and Ang2 alone and in combination.
      Furthermore VEGF/Ang2-induced EC invasion, angiogenesis and migration were
      inhibited by Notch-1 siRNA or DAPT. Conditioned media from VEGF/Ang2 stimulated
      RA synovial explants induced EC tube formation, an effect that was inhibited by
      DAPT. Finally, DAPT significantly decreased VEGF/Ang2 induced IL-6, IL-8, MMP2
      and 9 expressions in RA synovial explants. CONCLUSIONS: Notch-1 mediates
      VEGF/Ang2-induced angiogenesis and EC invasion in inflammatory arthritis.

PMID- 23161902
TI  - Clinical efficacy, radiographic and safety findings through 2 years of golimumab
      treatment in patients with active psoriatic arthritis: results from a long-term
      extension of the randomised, placebo-controlled GO-REVEAL study.
AB  - OBJECTIVES: To assess long-term golimumab efficacy/safety in patients with active
      psoriatic arthritis (PsA). METHODS: Adult PsA patients (>=3 swollen, >=3 tender
      joints, active psoriasis) were randomly assigned to subcutaneous injections of
      placebo, golimumab 50 mg or 100 mg every 4 weeks (q4wks) through week 20. All
      patients received golimumab 50 or 100 mg beginning week 24. Findings through 2
      years are reported. Efficacy evaluations included >=20% improvement in American
      College of Rheumatology (ACR20) response, good/moderate response in Disease
      Activity Scores incorporating 28 joints and C-reactive protein (DAS28-CRP), >=75%
      improvement in Psoriasis Area and Severity Index (PASI75) and changes in PsA
      modified Sharp/van der Heijde scores (SHS). RESULTS: Golimumab treatment through
      2 years was effective in maintaining clinical response (response rates: ACR20 63%
      70%, DAS28-CRP 77%-86%, PASI75 56%-72%) and inhibiting radiographic progression
      (mean change in PsA-modified SHS in golimumab-treated patients: -0.36), with no
      clear difference between doses. No new safety signals were identified through 2
      years. With the study's tuberculosis screening and prophylactic measures, no
      patient developed active tuberculosis through 2 years. CONCLUSIONS: Golimumab 50
      and 100 mg for up to 2 years yielded sustained clinical and radiographic efficacy
      when administered to patients with active PsA. Increasing the golimumab dose from
      50 to 100 mg q4wks added limited benefit. Golimumab safety through up to 2 years
      was consistent with other antitumour necrosis factor alpha agents used to treat
      PsA. Treatment of patients with latent tuberculosis identified at baseline
      appeared to be effective in inhibiting the development of active tuberculosis.

PMID- 23161903
TI  - Critical role of the adhesion receptor DNAX accessory molecule-1 (DNAM-1) in the
      development of inflammation-driven dermal fibrosis in a mouse model of systemic
      sclerosis.
AB  - OBJECTIVE: To investigate the contribution of the adhesion receptor DNAX
      accessory molecule-1 (DNAM-1) in the development of dermal fibrosis on gene
      inactivation and targeted molecular strategies. METHODS: Human skin expression of
      DNAM-1 was determined by immunohistochemistry. Mice deficient for DNAM-1 (dnam1-/
      ) and wild-type controls (dnam1+/+) were injected with bleomycin or NaCl.
      Infiltrating leucocytes, T cells, B cells and monocytes were quantified and
      inflammatory cytokines were measured in lesional skin of dnam1-/- and dnam1+/+
      mice. The anti-fibrotic potential of a DNAM-1 neutralising monoclonal antibody
      (mAb) was evaluated in the mouse model of bleomycin-induced dermal fibrosis.
      RESULTS: Overexpression of DNAM-1 was detected in the skin of patients with SSc
      (systemic sclerosis). Dnam1-/- mice were protected from bleomycin-induced dermal
      fibrosis with reduction of dermal thickening (75+/-5%, p=0.03), hydroxyproline
      content (46+/-8%, p=0.04) and myofibroblast counts (39+/-5%, p=0.01). Moreover,
      the number of T cells was significantly decreased in lesional skin of dnam1-/-
      mice (69+/-15%, p=0.0007). Dnam1-/- mice also displayed decreased levels of TNF
      alpha and IL-6 in lesional skin. Consistent with the gene inactivation strategy,
      treatment of mice with DNAM-1 neutralising mAb prevented dermal fibrosis induced
      by bleomycin with reduction of dermal thickness (64+/-6%, p=0.002),
      hydroxyproline content (61+/-8%, p=0.004) and myofibroblast counts (83+/-12%,
      p=0.002). CONCLUSIONS: An inactivation gene strategy showed that DNAM-1 exerts
      profibrotic effects by controlling T cell activation and cytokine release. A
      molecular targeted strategy confirmed that DNAM-1 neutralising mAb has potent
      antifibrotic properties, supporting the hypothesis that inhibition of DNAM-1
      might be a promising new approach for the treatment of SSc and potentially other
      related fibrotic diseases.

PMID- 23161904
TI  - Bone oedema on MRI is highly associated with low bone mineral density in patients
      with early inflammatory back pain: results from the DESIR cohort.
AB  - OBJECTIVES: To assess bone mineral density (BMD) at lumbar spine and hip in a
      large cohort of patients with early inflammatory back pain (IBP) suggestive of
      axial spondyloarthritis (SpA), and to assess systemic and bone inflammation
      (according to MRI) as risk factors of low BMD. PATIENTS AND METHODS: 332 (52.4%
      male) patients with IBP suggestive of axial SpA defined by Calin or Berlin
      criteria were recruited; they had lumbar spine and hip BMD and body composition
      measurements. Low BMD was defined by Z<=-2 (at least one site). Clinical,
      biological (erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP))
      and imaging (x-rays, spine and sacroiliac joint MRI) parameters were compared in
      patients with and without low BMD (Z<=-2). Significant parameters in univariate
      analysis were tested in multivariate models. RESULTS: Patients (mean age 33.8
      years) had a short duration of axial symptoms (mean 1.6 years); 71.4% fulfilled
      the Assessment of Spondyloarthritis International Society criteria for axial SpA
      and HLA-B27 was present in 62.1%. 43 (13.0%) had low BMD (88% male). Multivariate
      logistic regression showed that parameters significantly associated with low BMD
      (any site) were the presence of bone marrow oedema (inflammatory lesions) on MRI
      (OR 4.63, p=0.001), either ESR or CRP (OR 2.60, p=0.037) and male gender (OR
      9.60, p=0.0004). CONCLUSIONS: This study conducted in a large cohort of young
      adults with early IBP suggestive of SpA shows that 13.0% of patients have a low
      BMD and that the main risk factor associated with low BMD was inflammation on
      MRI.

PMID- 23161905
TI  - Neuroendocrine cell hyperplasia of infancy: a prospective follow-up of nine
      children.
AB  - Neuroendocrine cell hyperplasia of infancy (NEHI) has recently been described as
      an obstructive airway disease that affects infants aged 1-24 months, and presents
      typically with tachypnoea, crackles and hypoxia. The pathogenesis of the disease
      is unknown. We describe the clinical course of nine infants with radiologically
      and histologically confirmed NEHI. Host or environmental factors were not
      associated with the disease development. All infants with lung function tests
      demonstrated findings consistent with severe irreversible peripheral airway
      obstruction, assessed with whole body plethysmography (6/6) or the rapid
      thoracoabdominal compression technique (5/5). While the symptoms abated in all
      infants, six infants developed a non-atopic asthma during the follow-up. Systemic
      or inhaled corticosteroid treatment did not affect the duration of the symptoms.
      NEHI may mimic severe asthma and thus this entity should be taken into account
      when evaluating infants with chronic respiratory symptoms.

PMID- 23161906
TI  - Importance of freshwater injections into the Arctic Ocean in triggering the
      Younger Dryas cooling.

PMID- 23161907
TI  - Structural features underlying T-cell receptor sensitivity to concealed MHC class
      I micropolymorphisms.
AB  - Polymorphic differences distinguishing MHC class I subtypes often permit the
      presentation of shared epitopes in conformationally identical formats but can
      affect T-cell repertoire selection, differentially impacting autoimmune
      susceptibilities and viral clearance in vivo. The molecular mechanisms underlying
      this effect are not well understood. We performed structural, thermodynamic, and
      functional analyses of a conserved T-cell receptor (TCR) which is frequently
      expanded in response to a HIV-1 epitope when presented by HLA-B*5701 but is not
      selected by HLA-B*5703, which differs from HLA-B*5701 by two concealed
      polymorphisms. Our findings illustrate that although both HLA-B*57 subtypes
      display the epitope in structurally conserved formats, the impact of their
      polymorphic differences occurs directly as a consequence of TCR ligation,
      primarily because of peptide adjustments required for TCR binding, which involves
      the interplay of polymorphic residues and water molecules. These minor
      differences culminate in subtype-specific differential TCR-binding kinetics and
      cellular function. Our data demonstrate a potential mechanism whereby the most
      subtle MHC class I micropolymorphisms can influence TCR use and highlight their
      implications for disease outcomes.

PMID- 23161908
TI  - Structure of the formin-interaction domain of the actin nucleation-promoting
      factor Bud6.
AB  - Formin proteins and their associated factors cooperate to assemble unbranched
      actin filaments in diverse cellular structures. The Saccharomyces cerevisiae
      formin Bni1 and its associated nucleation-promoting factor (NPF) Bud6 generate
      actin cables and mediate polarized cell growth. Bud6 binds to both the tail of
      the formin and G-actin, thereby recruiting monomeric actin to the formin to
      create a nucleation seed. Here, we structurally and functionally dissect the
      nucleation-promoting C-terminal region of Bud6 into a Bni1-binding "core" domain
      and a G-actin binding "flank" domain. The ~2-A resolution crystal structure of
      the Bud6 core domain reveals an elongated dimeric rod with a unique fold
      resembling a triple-helical coiled-coil. Binding and actin-assembly assays show
      that conserved residues on the surface of this domain mediate binding to Bni1 and
      are required for NPF activity. We find that the Bni1 dimer binds two Bud6 dimers
      and that the Bud6 flank binds a single G-actin molecule. These findings suggest a
      model in which a Bni1/Bud6 complex with a 2:4 subunit stoichiometry assembles a
      nucleation seed with Bud6 coordinating up to four actin subunits.

PMID- 23161909
TI  - Phycoerythrin-specific bilin lyase-isomerase controls blue-green chromatic
      acclimation in marine Synechococcus.
AB  - The marine cyanobacterium Synechococcus is the second most abundant
      phytoplanktonic organism in the world's oceans. The ubiquity of this genus is in
      large part due to its use of a diverse set of photosynthetic light-harvesting
      pigments called phycobiliproteins, which allow it to efficiently exploit a wide
      range of light colors. Here we uncover a pivotal molecular mechanism underpinning
      a widespread response among marine Synechococcus cells known as "type IV
      chromatic acclimation" (CA4). During this process, the pigmentation of the two
      main phycobiliproteins of this organism, phycoerythrins I and II, is reversibly
      modified to match changes in the ambient light color so as to maximize photon
      capture for photosynthesis. CA4 involves the replacement of three molecules of
      the green light-absorbing chromophore phycoerythrobilin with an equivalent number
      of the blue light-absorbing chromophore phycourobilin when cells are shifted from
      green to blue light, and the reverse after a shift from blue to green light. We
      have identified and characterized MpeZ, an enzyme critical for CA4 in marine
      Synechococcus. MpeZ attaches phycoerythrobilin to cysteine-83 of the alpha
      subunit of phycoerythrin II and isomerizes it to phycourobilin. mpeZ RNA is six
      times more abundant in blue light, suggesting that its proper regulation is
      critical for CA4. Furthermore, mpeZ mutants fail to normally acclimate in blue
      light. These findings provide insights into the molecular mechanisms controlling
      an ecologically important photosynthetic process and identify a unique class of
      phycoerythrin lyase/isomerases, which will further expand the already widespread
      use of phycoerythrin in biotechnology and cell biology applications.

PMID- 23161910
TI  - Progress on first-principles-based materials design for hydrogen storage.
AB  - This article briefly summarizes the research activities in the field of hydrogen
      storage in sorbent materials and reports our recent works and future directions
      for the design of such materials. Distinct features of sorption-based hydrogen
      storage methods are described compared with metal hydrides and complex chemical
      hydrides. We classify the studies of hydrogen sorbent materials in terms of two
      key technical issues: (i) constructing stable framework structures with high
      porosity, and (ii) increasing the binding affinity of hydrogen molecules to
      surfaces beyond the usual van der Waals interaction. The recent development of
      reticular chemistry is summarized as a means for addressing the first issue.
      Theoretical studies focus mainly on the second issue and can be grouped into
      three classes according to the underlying interaction mechanism: electrostatic
      interactions based on alkaline cations, Kubas interactions with open transition
      metals, and orbital interactions involving Ca and other nontransitional metals.
      Hierarchical computational methods to enable the theoretical predictions are
      explained, from ab initio studies to molecular dynamics simulations using force
      field parameters. We also discuss the actual delivery amount of stored hydrogen,
      which depends on the charging and discharging conditions. The usefulness and
      practical significance of the hydrogen spillover mechanism in increasing the
      storage capacity are presented as well.

PMID- 23161912
TI  - Hurricanes and rising global temperatures.

PMID- 23161911
TI  - Cyclin D1 overexpression supports stable EBV infection in nasopharyngeal
      epithelial cells.
AB  - Undifferentiated nasopharyngeal carcinomas (NPCs) are commonly present with
      latent EBV infection. However, events regulating EBV infection at early stages of
      the disease and the role of EBV in disease pathogenesis are largely undefined.
      Genetic alterations leading to activation of cyclin D1 signaling in premalignant
      nasopharyngeal epithelial (NPE) cells have been postulated to predispose cells to
      EBV infection. We previously reported that loss of p16, a negative regulator of
      cyclin D1 signaling, is a frequent feature of NPC tumors. Here, we report that
      early premalignant lesions of nasopharyngeal epithelium overexpress cyclin D1.
      Furthermore, overexpression of cyclin D1 is closely associated with EBV
      infection. Therefore we investigated the potential role of cyclin D1
      overexpression in dysplastic NPE cells in vitro. In human telomerase reverse
      transcriptase-immortalized NPE cells, overexpression of cyclin D1 or a p16
      resistant form of CDK4 (CDK4(R24C)) suppressed differentiation. This suppression
      may have implications for the close association of EBV infection with
      undifferentiated NPC. In these in vitro models, we found that cellular growth
      arrest and senescence occurred in EBV-infected cell populations immediately after
      infection. Nevertheless, overexpression of cyclin D1 or a p16-resistant form of
      CDK4 or knockdown of p16 in the human telomerase reverse transcriptase
      immortalized NPE cell lines could counteract the EBV-induced growth arrest and
      senescence. We conclude that dysregulated expression of cyclin D1 in NPE cells
      may contribute to NPC pathogenesis by enabling persistent infection of EBV.

PMID- 23161914
TI  - Obstructive sleep apnoea in adults.
AB  - Obstructive sleep apnoea (OSA) is characterised by repetitive closure of the
      upper airway, repetitive oxygen desaturations and sleep fragmentation. The
      prevalence of adult OSA is increasing because of a worldwide increase in obesity
      and the ageing of populations. OSA presents with a variety of symptoms the most
      prominent of which are snoring and daytime tiredness. Interestingly though, a
      significant proportion of OSA sufferers report little or no daytime symptoms. OSA
      has been associated with an increased risk of cardiovascular disease, cognitive
      abnormalities and mental health problems. Randomised controlled trial evidence is
      awaited to confirm a causal relationship between OSA and these various disorders.
      The gold standard diagnostic investigation for OSA is overnight laboratory-based
      polysomnography (sleep study), however, ambulatory models of care incorporating
      screening questionnaires and home sleep studies have been recently evaluated and
      are now being incorporated into routine clinical practice. Patients with OSA are
      very often obese and exhibit a range of comorbidities, such as hypertension,
      depression and diabetes. Management, therefore, needs to be based on a
      multidisciplinary and holistic approach which includes lifestyle modifications.
      Continuous positive airway pressure (CPAP) is the first-line therapy for severe
      OSA. Oral appliances should be considered in patients with mild or moderate
      disease, or in those unable to tolerate CPAP. New, minimally invasive surgical
      techniques are currently being developed to achieve better patient outcomes and
      reduce surgical morbidity. Successful long-term management of OSA requires
      careful patient education, enlistment of the family's support and the adoption of
      self-management and patient goal-setting principles.

PMID- 23161913
TI  - Rational design of potent domain antibody inhibitors of amyloid fibril assembly.
AB  - Antibodies hold significant potential for inhibiting toxic protein aggregation
      associated with conformational disorders such as Alzheimer's and Huntington's
      diseases. However, near-stoichiometric antibody concentrations are typically
      required to completely inhibit protein aggregation. We posited that the molecular
      interactions mediating amyloid fibril formation could be harnessed to generate
      antibodies with potent antiaggregation. Here we report that grafting small
      amyloidogenic peptides (6-10 residues) into the complementarity-determining
      regions of a single-domain (V(H)) antibody yields potent domain antibody
      inhibitors of amyloid formation. Grafted AMyloid-Motif AntiBODIES (gammabodies)
      presenting hydrophobic peptides from Abeta (Alzheimer's disease), alpha-Synuclein
      (Parkinson's disease), and islet amyloid polypeptide (type 2 diabetes) inhibit
      fibril assembly of each corresponding polypeptide at low substoichiometric
      concentrations (1:10 gammabody:monomer molar ratio). In contrast, sequence- and
      conformation-specific antibodies that were obtained via immunization are unable
      to prevent fibrillization at the same substoichiometric concentrations.
      Gammabodies prevent amyloid formation by converting monomers and/or fibrillar
      intermediates into small complexes that are unstructured and benign. We expect
      that our antibody design approach--which eliminates the need for immunization or
      screening to identify sequence-specific domain antibody inhibitors--can be
      readily extended to generate potent aggregation inhibitors of other amyloidogenic
      polypeptides linked to human disease.

PMID- 23161915
TI  - Preparation and functional evaluation of RGD-modified streptavidin targeting to
      integrin-expressing melanoma cells.
AB  - The vertical growth stage is the most dangerous stage of melanoma and is often
      associated with a poor prognosis. The increased invasiveness and metastasis that
      is typical for vertically growing melanoma are mediated by the molecules of cell
      adhesion (particularly, integrins). Integrin alphavbeta3, which is abundantly
      expressed on melanoma cells with high metastatic potentials and is characterized
      by low expression levels in normal melanocytes, is potentially an attractive
      target for melanoma diagnostics and therapy. Integrin alphavbeta3 is known to
      recognize the arginine-glycine-aspartic (RGD) sequence, which has been found in a
      wide variety of its natural ligands. Here expression vectors bearing the genes of
      fusion proteins have been constructed for producing these proteins in Escherichia
      coli. Such fusion proteins consist of a peptidic 'address,' targeting the
      integrins on melanoma cells, linked to an 'adaptor' for the attachment of a
      diagnostic or toxic agent. The peptidic 'address' contains the RGD motif, which
      is stabilized by a disulfide bond to achieve the optimal receptor binding
      conformation. The 'adaptor' is a tetrameric protein, namely, streptavidin, that
      is able to achieve high-affinity binding of d-biotin (K(d) = 10(-15) M) and
      confer avidity to the address peptide. This binding ability facilitates the
      generation of anti-melanoma diagnostic and therapeutic agents using the
      appropriate biotin derivatives. These recombinant proteins were purified from the
      periplasm of E.coli using columns with 2-iminobiotin agarose and demonstrated an
      ability to adhere to the surface of murine and human melanoma cells.

PMID- 23161917
TI  - Wellbeing report highlights lack of understanding of pets' needs.

PMID- 23161919
TI  - Practice Standards Scheme: RCVS seeks views on the way forward.

PMID- 23161916
TI  - Engineering a soluble high-affinity receptor domain that neutralizes
      staphylococcal enterotoxin C in rabbit models of disease.
AB  - Superantigens (SAgs) are a class of immunostimulatory exotoxins that activate
      large numbers of T cells, leading to overproduction of cytokines and subsequent
      inflammatory reactions and systemic toxicity. Staphylococcal enterotoxin C (SEC),
      a SAg secreted by Staphylococcus aureus, has been implicated in various illnesses
      including non-menstrual toxic shock syndrome (TSS) and necrotizing pneumonia. SEC
      has been shown to cause TSS illness in rabbits and the toxin contributes to
      lethality associated with methicillin-resistant S.aureus (MRSA) in a rabbit model
      of pneumonia. With the goal of reducing morbidity and mortality associated with
      SEC, a high-affinity variant of the extracellular variable domain of the T-cell
      receptor beta-chain for SEC (~14 kDa) was generated by directed evolution using
      yeast display. This protein was characterized biochemically and shown to cross
      react with the homologous (65% identical) SAg staphylococcal enterotoxin B (SEB).
      The soluble, high-affinity T-cell receptor protein neutralized SEC and SEB in
      vitro and also significantly reduced the bacterial burden of an SEC-positive
      strain of MRSA (USA400 MW2) in an infective endocarditis model. The neutralizing
      agent also prevented lethality due to MW2 in a necrotizing pneumonia rabbit
      model. These studies characterize a soluble high-affinity neutralizing agent
      against SEC, which is cross-reactive with SEB, and that has potential to be used
      intravenously with antibiotics to manage staphylococcal diseases that involve
      these SAgs.

PMID- 23161920
TI  - Memorial service for animals serving in military conflicts.

PMID- 23161921
TI  - Calls to restrict veterinary use of antimicrobials.

PMID- 23161923
TI  - 'Incredible year' celebrated at AHT Equestrian Awards.

PMID- 23161925
TI  - Partnership to foster research and education.

PMID- 23161927
TI  - Doing right by companion animals.

PMID- 23161928
TI  - Further outbreaks of blackleg seen across Scotland.

PMID- 23161929
TI  - Easier and earlier detection of lameness in dairy cows.

PMID- 23161930
TI  - Delivering a healthy Royal College.

PMID- 23161931
TI  - New UK vet school.

PMID- 23161932
TI  - Disease associated with immature paramphistome infection.

PMID- 23161933
TI  - Treatment of contagious bovine pleuropneumonia.

PMID- 23161934
TI  - Schmallenberg virus milk antibody ELISA.

PMID- 23161935
TI  - Study to investigate the use of fine needle aspiration techniques.

PMID- 23161949
TI  - Responsible research conduct.

PMID- 23161963
TI  - Global health. Disappointing results blunt hopes for malaria vaccine.

PMID- 23161964
TI  - Europe. Researchers lobby to spare science from E.U. budget cuts.

PMID- 23161965
TI  - Research philanthropy. Billionaire restores funding for novel biomedical network.

PMID- 23161966
TI  - U.S. election. Old challenges, new faces await science community in 2013.

PMID- 23161967
TI  - U.S. election. Change versus experience?

PMID- 23161968
TI  - Ecology. Nearly buried, mussels get a helping hand.

PMID- 23161969
TI  - Ecology. The evolutionary allure of mussels.

PMID- 23161970
TI  - Climate change. Winds of change.

PMID- 23161971
TI  - Climate change. Slip sliding away.

PMID- 23161972
TI  - Small science: radical innovation.

PMID- 23161973
TI  - Small science: view from developing nations.

PMID- 23161974
TI  - Small science: big science will prevail.

PMID- 23161975
TI  - Small science: high stakes.

PMID- 23161976
TI  - Disease prevention: experiments in nature.

PMID- 23161977
TI  - Disease prevention: vitamin D trials.

PMID- 23161980
TI  - Sustainability. The green economy post Rio+20.

PMID- 23161981
TI  - Cell biology. Promoting tumorigenesis by suppressing autophagy.

PMID- 23161982
TI  - Chemistry. Functional DNA origami devices.

PMID- 23161983
TI  - Immunology. Cooperative transcription factor complexes in control.

PMID- 23161984
TI  - Materials science. Speeding up artificial muscles.

PMID- 23161985
TI  - Evolution. Convergent evolution of hearing.

PMID- 23161986
TI  - Archaeology. Mediterranean island voyages.

PMID- 23161987
TI  - Planetary science. A vitrage of asteroid magnetism.

PMID- 23161988
TI  - Biomaterials. Introduction.

PMID- 23161989
TI  - China's push in tissue engineering.

PMID- 23161991
TI  - Soft matter models of developing tissues and tumors.
AB  - Analogies with inert soft condensed matter--such as viscoelastic liquids, pastes,
      foams, emulsions, colloids, and polymers--can be used to investigate the
      mechanical response of soft biological tissues to forces. A variety of
      experimental techniques and biophysical models have exploited these analogies
      allowing the quantitative characterization of the mechanical properties of model
      tissues, such as surface tension, elasticity, and viscosity. The framework of
      soft matter has been successful in explaining a number of dynamical tissue
      behaviors observed in physiology and development, such as cell sorting, tissue
      spreading, or the escape of individual cells from a tumor. However, living
      tissues also exhibit active responses, such as rigidity sensing or cell
      pulsation, that are absent in inert soft materials. The soft matter models
      reviewed here have provided valuable insight in understanding morphogenesis and
      cancer invasion and have set bases for using tissue engineering within medicine.

PMID- 23161990
TI  - Multifunctional nanoparticles: cost versus benefit of adding targeting and
      imaging capabilities.
AB  - Nanoparticle-based drug delivery systems have been developed to improve the
      efficacy and reduce the systemic toxicity of a wide range of drugs. Although
      clinically approved nanoparticles have consistently shown value in reducing drug
      toxicity, their use has not always translated into improved clinical outcomes.
      This has led to the development of "multifunctional" nanoparticles, where
      additional capabilities like targeting and image contrast enhancement are added
      to the nanoparticles. However, additional functionality means additional
      synthetic steps and costs, more convoluted behavior and effects in vivo, and also
      greater regulatory hurdles. The trade-off between additional functionality and
      complexity is the subject of ongoing debate and the focus of this Review.

PMID- 23161992
TI  - Unlike bone, cartilage regeneration remains elusive.
AB  - Articular cartilage was predicted to be one of the first tissues to successfully
      be regenerated, but this proved incorrect. In contrast, bone (but also
      vasculature and cardiac tissues) has seen numerous successful reparative
      approaches, despite consisting of multiple cell and tissue types and, thus,
      possessing more complex design requirements. Here, we use bone-regeneration
      successes to highlight cartilage-regeneration challenges: such as selecting
      appropriate cell sources and scaffolds, creating biomechanically suitable
      tissues, and integrating to native tissue. We also discuss technologies that can
      address the hurdles of engineering a tissue possessing mechanical properties that
      are unmatched in human-made materials and functioning in environments unfavorable
      to neotissue growth.

PMID- 23161993
TI  - Printing and prototyping of tissues and scaffolds.
AB  - New manufacturing technologies under the banner of rapid prototyping enable the
      fabrication of structures close in architecture to biological tissue. In their
      simplest form, these technologies allow the manufacture of scaffolds upon which
      cells can grow for later implantation into the body. A more exciting prospect is
      the printing and patterning in three dimensions of all the components that make
      up a tissue (cells and matrix materials) to generate structures analogous to
      tissues; this has been termed bioprinting. Such techniques have opened new areas
      of research in tissue engineering and regenerative medicine.

PMID- 23161994
TI  - Electrically, chemically, and photonically powered torsional and tensile
      actuation of hybrid carbon nanotube yarn muscles.
AB  - Artificial muscles are of practical interest, but few types have been
      commercially exploited. Typical problems include slow response, low strain and
      force generation, short cycle life, use of electrolytes, and low energy
      efficiency. We have designed guest-filled, twist-spun carbon nanotube yarns as
      electrolyte-free muscles that provide fast, high-force, large-stroke torsional
      and tensile actuation. More than a million torsional and tensile actuation cycles
      are demonstrated, wherein a muscle spins a rotor at an average 11,500
      revolutions/minute or delivers 3% tensile contraction at 1200 cycles/minute.
      Electrical, chemical, or photonic excitation of hybrid yarns changes guest
      dimensions and generates torsional rotation and contraction of the yarn host.
      Demonstrations include torsional motors, contractile muscles, and sensors that
      capture the energy of the sensing process to mechanically actuate.

PMID- 23161995
TI  - Synthetic lipid membrane channels formed by designed DNA nanostructures.
AB  - We created nanometer-scale transmembrane channels in lipid bilayers by means of
      self-assembled DNA-based nanostructures. Scaffolded DNA origami was used to
      create a stem that penetrated and spanned a lipid membrane, as well as a barrel
      shaped cap that adhered to the membrane, in part via 26 cholesterol moieties. In
      single-channel electrophysiological measurements, we found similarities to the
      response of natural ion channels, such as conductances on the order of 1
      nanosiemens and channel gating. More pronounced gating was seen for mutations in
      which a single DNA strand of the stem protruded into the channel. Single-molecule
      translocation experiments show that the synthetic channels can be used to
      discriminate single DNA molecules.

PMID- 23161996
TI  - Coherent phonon heat conduction in superlattices.
AB  - The control of heat conduction through the manipulation of phonons as coherent
      waves in solids is of fundamental interest and could also be exploited in
      applications, but coherent heat conduction has not been experimentally confirmed.
      We report the experimental observation of coherent heat conduction through the
      use of finite-thickness superlattices with varying numbers of periods. The
      measured thermal conductivity increased linearly with increasing total
      superlattice thickness over a temperature range from 30 to 150 kelvin, which is
      consistent with a coherent phonon heat conduction process. First-principles and
      Green's function-based simulations further support this coherent transport model.
      Accessing the coherent heat conduction regime opens a new venue for phonon
      engineering for an array of applications.

PMID- 23161997
TI  - Evidence for a dynamo in the main group pallasite parent body.
AB  - Understanding the origin of pallasites, stony-iron meteorites made mainly of
      olivine crystals and FeNi metal, has been a vexing problem since their discovery.
      Here, we show that pallasite olivines host minute magnetic inclusions that have
      favorable magnetic recording properties. Our paleointensity measurements indicate
      strong paleomagnetic fields, suggesting dynamo action in the pallasite parent
      body. We use these data and thermal modeling to suggest that some pallasites
      formed when liquid FeNi from the core of an impactor was injected as dikes into
      the shallow mantle of a ~200-kilometer-radius protoplanet. The protoplanet
      remained intact for at least several tens of millions of years after the olivine
      metal mixing event.

PMID- 23161998
TI  - Evidence for early hafted hunting technology.
AB  - Hafting stone points to spears was an important advance in weaponry for early
      humans. Multiple lines of evidence indicate that ~500,000-year-old stone points
      from the archaeological site of Kathu Pan 1 (KP1), South Africa, functioned as
      spear tips. KP1 points exhibit fracture types diagnostic of impact. Modification
      near the base of some points is consistent with hafting. Experimental and metric
      data indicate that the points could function well as spear tips. Shape analysis
      demonstrates that the smaller retouched points are as symmetrical as larger
      retouched points, which fits expectations for spear tips. The distribution of
      edge damage is similar to that in an experimental sample of spear tips and is
      inconsistent with expectations for cutting or scraping tools. Thus, early humans
      were manufacturing hafted multicomponent tools ~200,000 years earlier than
      previously thought.

PMID- 23161999
TI  - Pathological alpha-synuclein transmission initiates Parkinson-like
      neurodegeneration in nontransgenic mice.
AB  - Parkinson's disease is characterized by abundant alpha-synuclein (alpha-Syn)
      neuronal inclusions, known as Lewy bodies and Lewy neurites, and the massive loss
      of midbrain dopamine neurons. However, a cause-and-effect relationship between
      Lewy inclusion formation and neurodegeneration remains unclear. Here, we found
      that in wild-type nontransgenic mice, a single intrastriatal inoculation of
      synthetic alpha-Syn fibrils led to the cell-to-cell transmission of pathologic
      alpha-Syn and Parkinson's-like Lewy pathology in anatomically interconnected
      regions. Lewy pathology accumulation resulted in progressive loss of dopamine
      neurons in the substantia nigra pars compacta, but not in the adjacent ventral
      tegmental area, and was accompanied by reduced dopamine levels culminating in
      motor deficits. This recapitulation of a neurodegenerative cascade thus
      establishes a mechanistic link between transmission of pathologic alpha-Syn and
      the cardinal features of Parkinson's disease.

PMID- 23162000
TI  - Orbitofrontal cortex supports behavior and learning using inferred but not cached
      values.
AB  - Computational and learning theory models propose that behavioral control reflects
      value that is both cached (computed and stored during previous experience) and
      inferred (estimated on the fly on the basis of knowledge of the causal structure
      of the environment). The latter is thought to depend on the orbitofrontal cortex.
      Yet some accounts propose that the orbitofrontal cortex contributes to behavior
      by signaling "economic" value, regardless of the associative basis of the
      information. We found that the orbitofrontal cortex is critical for both value
      based behavior and learning when value must be inferred but not when a cached
      value is sufficient. The orbitofrontal cortex is thus fundamental for accessing
      model-based representations of the environment to compute value rather than for
      signaling value per se.

PMID- 23162001
TI  - A Rab32-dependent pathway contributes to Salmonella typhi host restriction.
AB  - Unlike other Salmonellae, the intracellular bacterial human pathogen Salmonella
      Typhi exhibits strict host specificity. The molecular bases for this restriction
      are unknown. Here we found that the expression of a single type III secretion
      system effector protein from broad-host Salmonella Typhimurium allowed Salmonella
      Typhi to survive and replicate within macrophages and tissues from mice, a
      nonpermissive host. This effector proteolytically targeted Rab32, which controls
      traffic to lysosome-related organelles in conjunction with components of the
      biogenesis of lysosome-related organelle complexes (BLOCs). RNA interference
      mediated depletion of Rab32 or of an essential component of a BLOC complex was
      sufficient to allow S. Typhi to survive within mouse macrophages. Furthermore, S.
      Typhi was able to survive in macrophages from mice defective in BLOC components.

PMID- 23162002
TI  - Salmonella inhibits retrograde trafficking of mannose-6-phosphate receptors and
      lysosome function.
AB  - Salmonella enterica is an intracellular bacterial pathogen that replicates within
      membrane-bound vacuoles through the action of effector proteins translocated into
      host cells. Salmonella vacuoles have characteristics of lysosomes but are reduced
      in hydrolytic enzymes transported by mannose-6-phosphate receptors (MPRs). We
      found that the effector SifA subverted Rab9-dependent retrograde trafficking of
      MPRs, thereby attenuating lysosome function. This required binding of SifA to its
      host cell target SKIP/PLEKHM2. Furthermore, SKIP regulated retrograde trafficking
      of MPRs in noninfected cells. Translocated SifA formed a stable complex with SKIP
      and Rab9 in infected cells. Sequestration of Rab9 by SifA-SKIP accounted for the
      effect of SifA on MPR transport and lysosome function. Growth of Salmonella
      increased in cells with reduced lysosomal activity and decreased in cells with
      higher lysosomal activity. These results suggest that Salmonella vacuoles undergo
      fusion with lysosomes whose potency has been reduced by SifA.

PMID- 23162003
TI  - Convergent evolution between insect and mammalian audition.
AB  - In mammals, hearing is dependent on three canonical processing stages: (i) an
      eardrum collecting sound, (ii) a middle ear impedance converter, and (iii) a
      cochlear frequency analyzer. Here, we show that some insects, such as rainforest
      katydids, possess equivalent biophysical mechanisms for auditory processing.
      Although katydid ears are among the smallest in all organisms, these ears perform
      the crucial stage of air-to-liquid impedance conversion and signal amplification,
      with the use of a distinct tympanal lever system. Further along the chain of
      hearing, spectral sound analysis is achieved through dispersive wave propagation
      across a fluid substrate, as in the mammalian cochlea. Thus, two phylogenetically
      remote organisms, katydids and mammals, have evolved a series of convergent
      solutions to common biophysical problems, despite their reliance on very
      different morphological substrates.

PMID- 23162004
TI  - Empirical evaluation of hand hygiene compliance.

PMID- 23162005
TI  - Photoplethysmography and continuous-wave Doppler ultrasound as a complementary
      test to ankle-brachial index in detection of stenotic peripheral arterial
      disease.
AB  - PURPOSE: We evaluated the sensitivity and specificity of ankle-brachial index
      (ABI), photoplethysmography (PPG), and continuous-wave Doppler ultrasound (CWD)
      in the detection of anatomically stenotic peripheral arterial disease (PAD).
      METHODS: Ninety-seven patients (194 legs) patients who had coincidentally
      undergone computed tomography angiography (CTA), ABI, PPG, and CWD for the
      evaluation of PAD were retrospectively reviewed. Sensitivity and specificity were
      measured. RESULTS: Among 194 legs, 163 (84%) legs had stenotic PAD on CTA.
      Overall sensitivity of ABI, PPG, and CWD was 69.3%, 81.6%, and 90.8% and
      specificity was 96.8%, 77.4%, and 64.5%, respectively. Ankle-brachial index
      showed a statistically significantly decreased sensitivity (14.8%) for below
      trifurcation level stenosis compared with CWD (92%) and PPG (67%). The
      sensitivity of ABI was also significantly decreased in single level and moderate
      stenosis (45.1% and 42.1%, respectively). In contrast, the sensitivity of CWD and
      PPG was not significantly decreased. CONCLUSION: The ABI showed significantly
      decreased sensitivity especially in stenosis below the trifurcation level. Both
      PPG and CWD were complementary to ABI in these groups of patients.

PMID- 23162006
TI  - An analysis of the relationship between ankle-brachial index and estimated
      glomerular filtration rate in type 2 diabetes.
AB  - We investigated the relationship between peripheral arterial disease (PAD) and
      renal function in patients with type 2 diabetes mellitus (T2DM). We enrolled 2057
      hospitalized patients with T2DM and measured kidney function and ankle-brachial
      index (ABI). The estimated glomerular filtration rate (eGFR) was derived using
      the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation and ABI
      was grouped as low (<0.9), low-normal (0.9-1.09), normal (1.1-1.3), and high
      (>1.3). Logistic regression was used to evaluate the associations of eGFR with
      ABI. Generally speaking, the ABI was negatively correlated with systolic blood
      pressure, fasting C-peptide, total cholesterol, and low-density lipoprotein
      cholesterol while positively correlated with body mass index (P < .05 to <.01).
      Only a low ABI was positively correlated with eGFR (P < .01). In addition to the
      association of the ABI with cardiovascular events, stroke, and PAD, ABI may also
      predict the change in renal function in patients with T2DM.

PMID- 23162008
TI  - Isolated nondominant right coronary stenosis: clinical presentation and
      management.
AB  - The frequency, clinical presentation, and management of severely stenotic
      isolated nondominant right coronary artery (NDRCA) have not been adequately
      defined. We sought to do so in a large cohort of patients undergoing coronary
      angiography. We retrospectively analyzed all patients who underwent coronary
      angiography in our institute between 1995 and June 2012, looking at those with a
      severe lesion in the NDRCA, recording demographic, clinical, and angiographic
      data. Of the 43,327 patients, 35 (0.08%) were found to have a severely stenotic
      NDRCA as a single-vessel disease. The most common indication for catheterization
      was acute coronary syndrome (49%). Most of the patients were managed
      conservatively (66%) and the entire group had a relatively benign course, with no
      coronary deaths. Severe stenosis of the NDRCA as isolated disease is a very rare
      entity, and although most commonly presenting with acute coronary syndrome,
      conservative management was the usual approach.

PMID- 23162007
TI  - First case report of familial hypercholesterolemia in an Omani family due to
      novel mutation in the low-density lipoprotein receptor gene.
AB  - Familial hypercholesterolemia (FH) is an autosomal dominant genetic disorder.
      Mutations have been found in at least 3 genes: the low-density lipoprotein
      receptor (LDLR), apolipoprotein B (APOB), and proprotein convertase
      subtilisin/kexin type 9 (PCSK9). We report the first case of FH in an Omani
      family due to a novel mutation in the LDLR gene. A 9-year-old female was referred
      to our lipid clinic with eye xanthelasmata and thickening of both Achilles
      tendons. Evaluation of the lipid profile showed the off treatment total
      cholesterol of 896 mg/dL (23.2 mmol/L), low-density lipoprotein cholesterol (LDL
      C) of 853 mg/dL (22.1 mmol/L), APOB of 4.5 g/L, triglyceride of 71 mg/dL (0.8
      mmol/L), and high-density lipoprotein cholesterol of 0.74 mmol/L. Genetic
      analysis of the LDLR gene showed a homozygous frameshift deletion mutation
      (272delG) at exon 3. The female patient was treated with a combination of
      rosuvastatin/ezetimibe and LDL apheresis.

PMID- 23162009
TI  - Socioeconomic inequality in the use of rituximab therapy among non-Hodgkin
      lymphoma patients in Chinese public hospitals.
AB  - Rituximab is a patient-paid effective monoclonal-antibody drug for non-Hodgkin
      lymphoma (NHL). Little is known in China, a country with unequal distribution of
      wealth and medical insurance systems, about the impact of socioeconomic status
      (SES) on selecting rituximab therapy in NHL patients. A total of 328 NHL
      inpatients in 2 public hospitals in Hangzhou were recruited and divided into 2
      equal groups: with rituximab therapy and with no rituximab therapy group.
      Selection and frequency of rituximab therapy increased with duration of education
      and in urban citizens (P < .01). Officers and businessmen were more likely to use
      rituximab therapy compared with farmers (P < .01). Patients covered by Urban
      Employee Basic Medical Insurance were more likely to select rituximab therapy
      than those insured with Urban-Rural Residents Basic Medical Insurance (P < .01).
      There was an inequality in provision of rituximab therapy among Chinese NHL
      patients, and this was associated with differences in SES status. Effective
      measures are suggested to ameliorate the inequality issue. 

PMID- 23162010
TI  - Sickness behavior in community-dwelling elderly: associations with impaired
      cardiac function and inflammation.
AB  - Sickness behavior is a cluster of symptoms that occur as a response to an
      infection and alterations in the inflammatory response. Under normal
      circumstances, sickness behavior is fully reversible once the pathogen has been
      cleared. Aging and chronic illness such as heart failure are associated with
      enhanced inflammatory activity that lasts for a long duration and no longer
      represents an adaptive response. The aim of this study was to explore whether
      inflammation mediates the relationship between impaired cardiac function and a
      symptom cluster including anhedonia, fatigue, and sleepiness, which might
      represent sickness behavior in community-dwelling elders. Structural equation
      modeling (SEM) showed that the factor impaired cardiac function (i.e., N-terminal
      fragment of pro-brain natriuretic peptide, left ventricular ejection fraction,
      and the heart failure medications angiotensin converting enzyme inhibitor,
      angiotensin receptor blockade, beta-blocker, and diuretics) was associated with
      both inflammation (i.e., C-reactive protein; beta = .26) and the symptom cluster
      (beta = .31). Inflammation had a significant direct, but smaller, association
      with the symptom cluster (beta = .21). By this pathway, inflammation also
      mediated an indirect association between impaired cardiac function and the
      symptom cluster (beta = .05). Including creatinine, blood glucose, ischemic heart
      disease, previous and current tumor, respiratory disease, age, and body mass
      index in the SEM model did not change these associations. Our results imply that
      some aspects of the symptom panorama in elderly individuals with impaired cardiac
      function or heart failure could represent sickness behavior. 

PMID- 23162011
TI  - Cadherin-11 regulates cell-cell tension necessary for calcific nodule formation
      by valvular myofibroblasts.
AB  - OBJECTIVE: Dystrophic calcific nodule formation in vitro involves differentiation
      of aortic valve interstitial cells (AVICs) into a myofibroblast phenotype.
      Interestingly, inhibition of the kinase MAPK Erk kinase (MEK)1/2 prevents
      calcific nodule formation despite leading to myofibroblast activation of AVICs,
      indicating the presence of an additional mechanotransductive component required
      for calcific nodule morphogenesis. In this study, we assess the role of
      transforming growth factor beta1-induced cadherin-11 expression in calcific
      nodule formation. METHODS AND RESULTS: As shown previously, porcine AVICs treated
      with transforming growth factor beta1 before cyclic strain exhibit increased
      myofibroblast activation and significant calcific nodule formation. In addition
      to an increase in contractile myofibroblast markers, transforming growth factor
      beta1-treated AVICs exhibit significantly increased expression of cadherin-11.
      This expression is inhibited by the addition of U0126, a specific MEK1/2
      inhibitor. The role of increased cadherin-11 is revealed through a wound assay,
      which demonstrates increased intercellular tension in transforming growth factor
      beta1-treated AVICs possessing cadherin-11. Furthermore, when small interfering
      RNA is used to knockdown cadherin-11, calcific nodule formation is abrogated,
      indicating that robust cell-cell connections are necessary in generating tension
      for calcific nodule morphogenesis. Finally, we demonstrate enrichment of cadherin
      11 in human calcified leaflets. CONCLUSIONS: These results indicate the necessity
      of cadherin-11 for dystrophic calcific nodule formation, which proceeds through
      an Erk1/2-dependent pathway.

PMID- 23162012
TI  - Aminotransferase levels are associated with cardiometabolic risk above and beyond
      visceral fat and insulin resistance: the Framingham Heart Study.
AB  - OBJECTIVE: We sought to characterize associations between aminotransferase levels
      and cardiometabolic risk after accounting for visceral adipose tissue and insulin
      resistance. METHODS AND RESULTS: Participants (n=2621) from the Framingham Heart
      Study (mean age 51, 49.8% women) were included. Sex-specific linear and logistic
      regressions were used to evaluate associations between aminotransferase levels
      and cardiometabolic risk factors. In multivariable models, increased alanine
      aminotransferase levels were associated with elevated blood pressure, fasting
      plasma glucose, and triglycerides and lower high-density lipoprotein levels (all
      P<=0.007). Furthermore, each 1-SD increase in alanine aminotransferase
      corresponded to an increased odds of hypertension, diabetes mellitus, the
      metabolic syndrome, impaired fasting glucose, and insulin resistance estimated by
      the homeostasis model assessment of insulin resistance (odds ratio, 1.29-1.85,
      all P<=0.002). Associations with alanine aminotransferase persisted after
      additional adjustment for visceral adipose tissue, insulin resistance, and body
      mass index with the exception of high-density lipoprotein cholesterol in both
      sexes and blood pressure in women. Results were materially unchanged when
      moderate drinkers were excluded, when the sample was restricted to those with
      alanine aminotransferase <40 U/L, and when the sample was restricted to those
      without diabetes mellitus. Similar trends were observed for aspartate
      aminotransferase levels, but associations were more modest. CONCLUSIONS:
      Aminotransferase levels are correlated with multiple cardiometabolic risk factors
      above and beyond visceral adipose tissue and insulin resistance.

PMID- 23162013
TI  - Loss of CDKN2B promotes p53-dependent smooth muscle cell apoptosis and aneurysm
      formation.
AB  - OBJECTIVE: Genomewide association studies have implicated allelic variation at
      9p21.3 in multiple forms of vascular disease, including atherosclerotic coronary
      heart disease and abdominal aortic aneurysm. As for other genes at 9p21.3, human
      expression quantitative trait locus studies have associated expression of the
      tumor suppressor gene CDKN2B with the risk haplotype, but its potential role in
      vascular pathobiology remains unclear. METHODS AND RESULTS: Here we used vascular
      injury models and found that Cdkn2b knockout mice displayed the expected increase
      in proliferation after injury, but developed reduced neointimal lesions and
      larger aortic aneurysms. In situ and in vitro studies suggested that these
      effects were attributable to increased smooth muscle cell apoptosis. Adoptive
      bone marrow transplant studies confirmed that the observed effects of Cdkn2b were
      mediated through intrinsic vascular cells and were not dependent on bone marrow
      derived inflammatory cells. Mechanistic studies suggested that the observed
      increase in apoptosis was attributable to a reduction in MDM2 and an increase in
      p53 signaling, possibly due in part to compensation by other genes at the 9p21.3
      locus. Dual inhibition of both Cdkn2b and p53 led to a reversal of the vascular
      phenotype in each model. CONCLUSIONS: These results suggest that reduced CDKN2B
      expression and increased smooth muscle cell apoptosis may be one mechanism
      underlying the 9p21.3 association with aneurysmal disease.

PMID- 23162014
TI  - Soluble CD14: genomewide association analysis and relationship to cardiovascular
      risk and mortality in older adults.
AB  - OBJECTIVE: CD14 is a glycosylphosphotidylinositol-anchored membrane glycoprotein
      expressed on neutrophils and monocytes/macrophages that also circulates as a
      soluble form (sCD14). Despite the well-recognized role of CD14 in inflammation,
      relatively little is known about the genetic determinants of sCD14 or the
      relationship of sCD14 to vascular- and aging-related phenotypes. METHODS AND
      RESULTS: We measured baseline levels of sCD14 in >5000 European-American and
      black adults aged 65 years and older from the Cardiovascular Health Study, who
      were well characterized at baseline for atherosclerotic risk factors and
      subclinical cardiovascular disease, and who have been followed for clinical
      cardiovascular disease and mortality outcomes up to 20 years. At baseline, sCD14
      generally showed strong positive correlations with traditional cardio-metabolic
      risk factors and with subclinical measures of vascular disease such as carotid
      wall thickness and ankle-brachial index (independently of traditional
      cardiovascular disease risk factors), and was also inversely correlated with body
      mass index. In genomewide association analyses of sCD14, we (1) confirmed the
      importance of the CD14 locus on chromosome 5q21 in European-American; (2)
      identified a novel African ancestry-specific allele of CD14 associated with lower
      sCD14 in blacks; and (3) identified a putative novel association in European
      American of a nonsynonymous variant of PIGC, which encodes an enzyme required for
      the first step in glycosylphosphotidylinositol anchor biosynthesis. Finally, we
      show that, like other acute phase inflammatory biomarkers, sCD14 predicts
      incident cardiovascular disease, and strongly and independently predicts all
      cause mortality in older adults. CONCLUSIONS: CD14 independently predicts risk
      mortality in older adults.

PMID- 23162015
TI  - Heterodimerization with the prostacyclin receptor triggers thromboxane receptor
      relocation to lipid rafts.
AB  - OBJECTIVE: Prostacyclin and thromboxane mediate opposing cardiovascular actions
      through receptors termed IP and TP, respectively. When dimerized with IP, the TP
      shifts to IP-like function. IP localizes to cholesterol-enriched membrane rafts,
      but TP and IPTP heterodimer localization is not defined. We examined these
      receptors' membrane localization and the role of rafts in receptor function.
      METHODS AND RESULTS: Microdomain distribution of IP, TP, and IPTP heterodimers
      was examined in COS-7 cells by measuring energy transfer from renilla luciferase
      fused receptors to fluorescently labeled rafts. IP raft association was
      confirmed. TP was raft excluded, but redistributed to rafts upon dimerization
      with IP. Signaling of the IP and IPTP heterodimer, but not TP alone, was
      suppressed after raft disruption by cholesterol depletion. Cholesterol enrichment
      also selectively suppressed IP and IPTP function. Native IP and IPTP signaling in
      smooth muscle cells and macrophages were similarly sensitive to cholesterol
      manipulation, whereas macrophages from hypercholesterolemic mice displayed
      suppressed IP and IPTP function. CONCLUSIONS: IP and TP function within distinct
      microdomains. Raft incorporation of TP in the IPTP heterodimer likely facilitates
      its signaling shift. We speculate that changes in IP and IPTP signaling after
      perturbation of membrane cholesterol may contribute to cardiovascular disease
      associated with hypercholesterolemia.

PMID- 23162017
TI  - Interleukin-33 drives a proinflammatory endothelial activation that selectively
      targets nonquiescent cells.
AB  - OBJECTIVE: Interleukin (IL)-33 is a nuclear protein that is released from
      stressed or damaged cells to act as an alarmin. We investigated the effects of IL
      33 on endothelial cells, using the prototype IL-1 family member, IL-1beta, as a
      reference. METHODS AND RESULTS: Human umbilical vein endothelial cells were
      stimulated with IL-33 or IL-1beta, showing highly similar phosphorylation of
      signaling molecules, induction of adhesion molecules, and transcription profiles.
      However, intradermally injected IL-33 elicited significantly less proinflammatory
      endothelial activation when compared with IL-1beta and led us to observe that
      quiescent endothelial cells (ppRb(low)p27(high)) were strikingly resistant to IL
      33. Accordingly, the IL-33 receptor was preferentially expressed in nonquiescent
      cells of low-density cultures, corresponding to selective induction of adhesion
      molecules and chemokines. Multiparameter phosphoflow cytometry confirmed that
      signaling driven by IL-33 was stronger in nonquiescent cells. Manipulation of
      nuclear IL-33 expression by siRNA or adenoviral transduction revealed no
      functional link between nuclear, endogenous IL-33, and exogenous IL-33
      responsiveness. CONCLUSIONS: In contrast to other inflammatory cytokines, IL-33
      selectively targets nonquiescent endothelial cells. By this novel concept,
      quiescent cells may remain nonresponsive to a proinflammatory stimulus that
      concomitantly triggers a powerful response in cells that have been released from
      contact inhibition.

PMID- 23162018
TI  - Can mean platelet volume be a new risk factor in portal venous thrombosis?
AB  - BACKGROUND: The aim of this study was to discuss the possibility of mean platelet
      volume (MPV) being a new risk factor in the etiology of portal venous thrombosis
      (PVT). METHODS: Study participants were categorized into 2 different groups:
      group I, control group (n = 35) and group II, PVT group (n = 34). Demographic
      data and MPV values were recorded retrospectively. RESULTS: No differences were
      determined between the 2 groups regarding hypertension, diabetes mellitus, and
      smoking (P > .05). The average hemoglobin levels were 10.8 +/- 2.1 in group II
      and 14.0 +/- 1.7 in group I (P < .001). Although the MPV levels of group II
      patients were 8.2 +/- 0.52, the average level in group I was determined as 7.8 +/
      0.62 (P = .012). In the performed receiver-operating characteristic (ROC)
      analysis, the cutoff value for patients with PVT for MPV was determined as 7.9
      (area under curve: 0.674), sensitivity as 70.6%, and specificity as 65.7% (P =
      .013). CONCLUSION: The current study shows that MPV is significantly higher in
      patients with PVT than in the control group.

PMID- 23162016
TI  - Macrophage activation by heparanase is mediated by TLR-2 and TLR-4 and associates
      with plaque progression.
AB  - OBJECTIVE: Factors and mechanisms that activate macrophages in atherosclerotic
      plaques are incompletely understood. We examined the capacity of heparanase to
      activate macrophages. METHODS AND RESULTS: Highly purified heparanase was added
      to mouse peritoneal macrophages and macrophage-like J774 cells, and the levels of
      tumor necrosis factor-alpha, matrix metalloproteinase-9, interlukin-1, and
      monocyte chemotactic protein-1 were evaluated by ELISA. Gene expression was
      determined by RT-PCR. Cells collected from Toll-like receptor-2 and Toll-like
      receptor-4 knockout mice were evaluated similarly. Heparanase levels in the
      plasma of patients with acute myocardial infarction, stable angina, and healthy
      subjects were determined by ELISA. Immunohistochemistry was applied to detect the
      expression of heparanase in control specimens and specimens of patients with
      stable angina or acute myocardial infarction. Addition or overexpression of
      heparanase variants resulted in marked increase in tumor necrosis factor-alpha,
      matrix metalloproteinase-9, interlukin-1, and monocyte chemotactic protein-1
      levels. Mouse peritoneal macrophages harvested from Toll-like receptor-2 or Toll
      like receptor-4 knockout mice were not activated by heparanase. Plasma heparanase
      level was higher in patients with acute myocardial infarction, compared with
      patients with stable angina and healthy subjects. Pathologic coronary specimens
      obtained from vulnerable plaques showed increased heparanase staining compared
      with specimens of stable plaque and controls. CONCLUSIONS: Heparanase activates
      macrophages, resulting in marked induction of cytokine expression associated with
      plaque progression toward vulnerability.

PMID- 23162019
TI  - Left ventricular assist device-induced coagulation and platelet activation and
      effect of the current anticoagulant therapy regimen.
AB  - Left ventricular assist devices (LVADs) are mechanical pumps that enhance cardiac
      function in patients with heart failure. In all, 7 patients with an LVADs (1.8
      international normalized ratio warfarin, 81 mg aspirin) were evaluated monthly
      for 3 months for platelet and coagulation activation (controls: 5 healthy adults
      and 5 patients having warfarin). Platelet works revealed greater inhibition of
      collagen (31.8% vs 7.9%; P = .004), arachidonate- (30.9% vs 8.2%; P = .001), and
      adenosine diphosphate- (10.9% vs 6.1%; P = .004)-induced platelet aggregation for
      LVADs. Thrombelastography (recalcified whole blood) showed inhibition of clot
      initiation time (R; 8.81 vs 6.02 min; P = .001) and stronger clot formation
      (maximum amplitude; 69.1 vs 64.9 mm; P = .016). Platelet function determined by
      plateletMapping and flow cytometry was within the normal range. The LVADs had
      increased ratio of von Willebrand Factor (vWF) antigen and vWF propeptide,
      indicating increased degradation of vWF (2.04 vs 1.44; P = .144). Coagulation and
      platelet activation caused by LVAD is suppressed by pharmacotherapy, yielding a
      profile similar to that of patients on warfarin alone.

PMID- 23162020
TI  - Neonatal stroke associated with de novo antiphospholipid antibody and homozygous
      1298C/C methylenetetrahydrofolate reductase mutation.
AB  - Antiphospholipid antibodies are a recognised prothrombotic risk factor associated
      with acute ischaemic infarction. Most autoimmune diseases are rare in infants,
      and in the neonatal period, autoimmunity is related to transplacental passage of
      maternal immunoglobulin G autoantibodies. Distinguishing between de novo and
      acquired autoimmunity has important therapeutic implications and is crucial for
      determining the prognosis. We present a case of a neonatal thrombotic stroke
      associated with de novo synthesis of antiphospholipid antibodies, a homozygous
      1298C/C methylene-tetrahydrofolate reductase mutation and a double-homozygous
      plasminogen activator inhibitor 1 polymorphism (PAI-1 844A/A and 675 4G/4G),
      which may have increased the final thrombotic risk. Her mother was not positive
      for antiphospholipid antibodies. The authors highlight an unequivocal evidence of
      a de novo case of paediatric antiphospholipid antibody syndrome and emphasise the
      need for a thorough investigation in cases of neonatal stroke including molecular
      thrombophilia study.

PMID- 23162022
TI  - Appendicular sarcoidosis mimicking acute appendicitis.
AB  - Appendicular sarcoidosis is a very rare cause of acute abdominal pain, with only
      seven cases reported previously in the literature. A 45-year-old woman, known to
      have sarcoidosis, presented to the emergency department with a 1-week history of
      epigastric and right iliac fossa abdominal pain. At diagnostic laparoscopy, an
      acutely inflamed appendix was found and removed as well as an omental mass which
      was biopsied. Subsequent histopathological examination of the appendix
      demonstrated appendicular sarcoidosis without acute appendicitis and chronic
      inflammatory changes in the omental biopsy. The patients' symptoms completely
      resolved postoperatively. It is important to undertake urgent operative
      intervention in patients with sarcoidosis who present with right iliac fossa
      pain, owing to the high risk of perforation.

PMID- 23162021
TI  - Primary retroperitoneal echinococcal cyst.
AB  - A 74-year-old man was admitted with right flank pain and discomfort lasting for 2
      months. CT scanning revealed a large retroperitoneal cystic mass. There were no
      cysts elsewhere. Serological testing revealed hydatid disease. Preoperatively he
      was treated by Albendazole 400 mg for 1 month and then underwent laparotomy. The
      entire mass was excised en bloc and intact and right hemicolectomy was
      simultaneously performed for excision of the adhered ascending colon. He
      recovered uneventfully and was discharged on the eighth day, Albendazole was
      given and follow-up visits were arranged for every 6 months. Total cystectomy in
      case of active echinococcal cysts remains the treatment of choice.

PMID- 23162023
TI  - An unusual intracardiac image.
AB  - One of the most serious complications in cardiovascular surgery is the
      unintentional deposit of material and surgical instruments. Very few articles
      portray these complications in children. This is not the case with regard to
      interventional and surgical cardiovascular procedures in adults. We report a case
      concerning a cystic heart image related to a cardiac iatrogenic foreign body in a
      girl of 14&emsp14;years. She has been operated 13&emsp14;years ago for patent
      ductus arteriosus and aortic stenosis and currently she is admitted for a
      cyanosis and a dyspnoea.

PMID- 23162024
TI  - Combined hamartoma of the retina and retinal pigment epithelium.
AB  - We report two cases of combined hamatoma of the retina and retinal pigment
      epithelium (CHR-RPE), illustrated with ultrasonography, optical coherence
      tomography, fundus fluorescein angiography and indocyanine green angiography
      images. CHR-RPE could clinically mimic several other retinal conditions. Failure
      to distinguish it from serious malignancies such as choroidal melanoma or
      retinoblastoma has led to unnecessary enucleation in the past. Through these case
      reports and a review of literature, we show the diagnostic features of CHR-RPE,
      its key differential diagnoses and the management options.

PMID- 23162025
TI  - The clinical management in familial adenomatous polyposis deserves continuous
      monitoring for thyroid carcinoma.
AB  - Papillary thyroid carcinoma is an extraintestinal manifestation of patients with
      familial adenomatous polyposis, mainly occurring in young women. Recent
      publications highlight that familial adenomatous polyposis-associated papillary
      thyroid carcinoma represents a distinct type of follicular cell neoplasm
      histologically characterised by cribriform-morular aspects, the incidence of
      which has probably been underestimated so far. We report a case history of
      familial adenomatous polyposis-associated papillary thyroid carcinoma occurring
      in a 55-year-old man with Gardner syndrome, underscoring the importance of
      careful ultrasound screening examination of the thyroid gland in this condition.

PMID- 23162026
TI  - Two unusual variants of Guillain-Barre syndrome.
AB  - Guillain-Barre syndrome (GBS) is a group of autoimmune diseases characterised by
      acute, acquired and immune-mediated polyneuroradiculopathy. A large number of
      clinical subtypes of GBS have been described over last 100 years since the first
      description of this syndrome. We report two such cases GBS variants--first, AMAN
      with brisk reflexes and second being acute motor axonal neuropathy with
      conduction block. Through this case report, we intend to make the treating
      physicians and neurologist aware of these rare variants so that such cases would
      be appropriately diagnosed and treated.

PMID- 23162027
TI  - A giant ovarian cyst.

PMID- 23162028
TI  - Retroperitoneal haematoma causing gastric outflow obstruction following
      endovascular repair of a ruptured abdominal aortic aneurysm.
AB  - A 74-year-old man presented with back pain and collapse. A ruptured infrarenal
      abdominal aortic aneurysm was successfully managed by endovascular aneurysm
      repair. Postoperatively, he developed gastric outlet obstruction owing to
      duodenal compression from the unevacuated retroperitoneal haematoma. In the
      absence of abdominal compartment syndrome, conservative management with gastric
      decompression and parenteral nutrition led to a full recovery.

PMID- 23162029
TI  - Extensive venous thrombosis in a healthy young man with a short inferior vena
      cava syndrome treated successfully with rivaroxaban.
AB  - We report a case of an incidental finding of congenital absence of the
      intrahepatic segment of the inferior vena cava (IVC) complicated by extensive
      bilateral deep venous thrombosis (DVT) with significant oedema following a long
      distance road trip. Initially the patient failed treatment with standard
      anticoagulation therapy with enoxaparin and warfarin. However, he has responded
      to the new oral antifactor-Xa anticoagulant (rivaroxaban). Within a few days,
      rivaroxaban improved the oedema and DVT. The significant features of this case
      are the unusual presentation, the poor response to initial standard
      anticoagulation therapy and the beneficial outcomes when managed with the novel
      new anticoagulant. The patient has continued the new treatment regularly for the
      last 12 months with good toleration and without side effects. This report
      presents the findings, management and outcomes in a case of extensive bilateral
      DVT in a previously healthy young man who was found to have a congenital short
      IVC.

PMID- 23162030
TI  - An aortoesophageal fistula in an elderly woman.

PMID- 23162031
TI  - An adverse event of suprapubic catheter SPC insertion. A call for updating the
      existing guidelines.
AB  - The suprapubic catheter (SPC) is a useful and widely used tool in urological
      practice. However, complications can arise from its insertion or ongoing care. We
      add to the literature a case of an adverse event of its insertion where it has
      gone through a vascular graft and recommending updating the SPC insertion
      guidelines.

PMID- 23162032
TI  - Isolated hepatic artery injury in blunt abdominal trauma presenting as upper
      gastrointestinal bleeding: treatment with transcatheter embolisation.
AB  - Liver injury in blunt abdominal trauma is common. However, not often does blunt
      trauma cause injury to the anatomical structures of the porta hepatis. Isolated
      injury of the hepatic artery has been rarely reported in the literature. Such
      injury may be lethal and requires immediate diagnosis and management. This report
      describes an unusual case of blunt abdominal trauma resulting in hepatic and
      gastroduodenal artery dissection, with pseudoaneurysm formation complicated by
      active upper gastrointestinal bleeding. The injury was managed by transcatheter
      embolisation. Awareness of this diagnosis should facilitate management of similar
      trauma cases.

PMID- 23162033
TI  - Haematological, neurological and electrocardiographic findings in secondary
      hypothermia.
AB  - The association between secondary hypothermia and pancytopaenia is uncommon. A
      young woman presented with chronic hypothermia (28.8-34.6 degrees C) secondary to
      surgical hypothalamic injury postcraniopharyingioma resection as a child.
      Associated findings included pancytopaenia (haemoglobin 8.1 g/dl, leucocytes
      3500/mm(3), platelets 63,000/mm(3)), ataxia, upper motor neuron signs, decreased
      level of consciousness and new ECG changes. An extensive evaluation failed to
      reveal any cause of pancytopaenia other than chronic hypothermia. The
      haematological and neurological changes improved after active rewarming.

PMID- 23162034
TI  - Biliary stent migration presenting with leg pain.
AB  - Although the therapeutic benefits of endoscopic retrograde
      cholangiopancreatography (ERCP) usually outweigh the risks, there can be rare
      complications, including stent migration leading to perforation, intestinal
      obstruction or penetration. An 87-year-old woman presented with symptomatic
      choledocholithiasis. Two previous endoscopic attempts at stone removal were
      unsuccessful. On repeat ERCP at our institution, multiple large stones were
      removed, but complete duct clearance could not be achieved. A plastic biliary
      stent was placed with plans to reattempt in 6&emsp14;weeks. Postoperatively, she
      had mild back pain radiating into her right leg that gradually worsened to the
      point where she was unable to ambulate. An abdominal CT scan showed the distal
      aspect of the biliary stent extending through the wall of the duodenum with the
      tip positioned within the right psoas muscle. The stent was successfully removed
      via a rat-toothed forceps. Our case illustrates an extremely rare complication of
      biliary stent placement.

PMID- 23162035
TI  - Use of a coronary sinus guiding sheath for placement of right ventricular lead in
      abnormal venous anatomy: a report of 2 cases.
AB  - Techniques of implanting pacing leads in the right ventricle (RV) have evolved
      over time and involve the use of preshaped stylets. However, in the presence of
      venous abnormalities, it could be very challenging to do the same. We describe
      two cases with complex superior vena caval (SVC) anatomy which could be
      negotiated only with the use of a slittable coronary sinus guiding sheath and
      successful placement of pacing lead in the right ventricle.

PMID- 23162036
TI  - Direct thrombus aspiration using the Penumbra system for the treatment of
      pediatric intracranial dissection.
AB  - We describe a case of a 15-year-old girl who developed a spontaneous intracranial
      arterial dissection with distal middle cerebral artery (MCA) occlusions. From the
      digital subtraction angiography provided, the dissection flap appeared to
      originate at the internal carotid artery terminus with extension into the right
      M1 segment and occluding the right anterior cerebral artery, A1 segment. CT
      perfusion study showed salvageable tissue in the posterior MCA territory,
      including the motor cortex. In order to avoid further injury to the dissection,
      clot retrieval systems were not a treatment option. We therefore performed
      selective thrombus aspiration with the Penumbra system for the occluded central
      and precentral arteries distal to the non-occlusive dissecting lesion. Sufficient
      recanalization was achieved and the patient made a marked recovery. Although
      mechanical thrombectomy with the use of retrieval intracranial stent systems has
      demonstrated satisfactory recanalization rates, the aspiration methodology
      remains useful for patients with an accompanying proximal vascular lesion.

PMID- 23162038
TI  - Cerebral hyperperfusion after flow diversion of large intracranial aneurysms.
AB  - Cerebral hyperperfusion syndrome has been proposed to be caused by rapidly
      increased blood flow into chronically hypoperfused parenchyma with resultant
      impaired autoregulation, and has been noted after clipping of intracranial
      aneurysms and carotid stenting. The occurrence of the syndrome after endovascular
      flow diversion, however, has not been previously described. A 52-year-old woman
      was admitted electively for flow diverter treatment of a recurrent ventral
      paraclinoid aneurysm arising within a dysplastic segment of the left internal
      carotid artery. During the immediate postprocedural period the patient was found
      to have confusion, right hemiparesis, facial droop and dysarthria, which resolved
      with blood pressure control. Subsequent CT perfusion on day 11 demonstrated
      mildly elevated cerebral blood flow, cerebral blood volume and permeability
      values in the left hemisphere.

PMID- 23162037
TI  - Treatment of a pediatric recurrent fusiform middle cerebral artery (MCA) aneurysm
      with a flow diverter.
AB  - Pediatric patients with aneurysm often have different localizations and
      morphologies from adults and recurrences are not uncommon after successful clip
      reconstruction/obliteration. Treatment of a recurrent pediatric aneurysm after
      clip ligation is a technical challenge. We present the case of an adolescent with
      a middle cerebral artery (MCA) fusiform aneurysm which recurred following clip
      reconstruction and bypass. The aneurysm was successfully treated with
      endovascular flow diversion.

PMID- 23162039
TI  - Verification of supraselective drug delivery for retinoblastoma using intra
      arterial gadolinium.
AB  - We present a description of retinoblastoma treated with supraselective intra
      arterial chemotherapy, demonstrating selective delivery of the infused
      chemotherapeutic agent into the tumor bed by MRI. A 7-month-old presented with
      group E (international classification) unilateral retinoblastoma. We treated the
      patient with several rounds of intra-ophthalmic artery melphalan. Gadolinium was
      infused along with melphalan to visualize the distribution of this
      chemotherapeutic drug. Intraoperative MRI was obtained within 15&emsp14;min after
      treatment and showed increased enhancement of the tumor and subretinal space. We
      demonstrate here that supraselective administration of chemotherapy into the
      ophthalmic artery appears to result in drug delivery to the tumor and subretinal
      space.

PMID- 23162040
TI  - Cognitive treatment of illness perceptions in patients with chronic low back
      pain: a randomized controlled trial.
AB  - BACKGROUND: Illness perceptions have been shown to predict patient activities.
      Therefore, studies of the effectiveness of a targeted illness-perception
      intervention on chronic nonspecific low back pain (CLBP) are needed. OBJECTIVE:
      The purpose of this study was to compare the effectiveness of treatment of
      illness perceptions against a waiting list for patients with CLBP. DESIGN: This
      was a prospectively registered randomized controlled trial with an assessor
      blinded for group allocation. SETTING: The study was conducted in an outpatient
      rehabilitation clinic. PARTICIPANTS: The participants were 156 patients (18-70
      years of age) with CLBP (>3 months). INTERVENTION: Patients were randomly
      assigned to either a treatment group or to a waiting list (control) group.
      Trained physical therapists and occupational therapists delivered 10 to 14 one
      hour treatment sessions according to the treatment protocol. MEASUREMENTS: The
      primary outcome measure was change in patient-relevant physical activities
      (patient-specific complaints questionnaire). The secondary outcome measures were
      changes in illness perceptions (illness perceptions questionnaire) and generic
      physical activity level (quebec back pain disability scale). Measurements were
      taken at baseline (0 weeks) and after treatment (18 weeks). RESULTS: A baseline
      adjusted analysis of covariance showed that there were statistically significant
      differences between intervention and control groups at 18 weeks for the change in
      patient-relevant physical activities. This was a clinically relevant change (19.1
      mm) for the intervention group. Statistically significant differences were found
      for the majority of illness perception scales. There were no significant
      differences in generic physical activity levels. LIMITATIONS: Longer-term
      effectiveness was not studied. CONCLUSIONS: This first trial evaluating cognitive
      treatment of illness perceptions concerning CLBP showed statistically significant
      and clinically relevant improvements in patient-relevant physical activities at
      18 weeks.

PMID- 23162041
TI  - Issues affecting the delivery of physical therapy services for individuals with
      critical illness.
AB  - Research supports the provision of physical therapy intervention and early
      mobilization in the management of patients with critical illness. However, the
      translation of care from that of well-controlled research protocols to routine
      practice can be challenging and warrants further study. Discussions in the
      critical care and physical therapy communities, as well as in the published
      literature, are investigating factors related to early mobilization such as
      transforming culture in the intensive care unit (ICU), encouraging
      interprofessional collaboration, coordinating sedation interruption with mobility
      sessions, and determining the rehabilitation modalities that will most
      significantly improve patient outcomes. Some variables, however, need to be
      investigated and addressed specifically by the physical therapy profession. They
      include assessing and increasing physical therapist competence managing patients
      with critical illness in both professional (entry-level) education programs and
      clinical settings, determining and providing an adequate number of physical
      therapists for a given ICU, evaluating methods of prioritization of patients in
      the acute care setting, and adding to the body of research to support specific
      functional outcome measures to be used with patients in the ICU. Additionally,
      because persistent weakness and functional limitations can exist long after the
      critical illness itself has resolved, there is a need for increased awareness and
      involvement of physical therapists in all settings of practice, including
      outpatient clinics. The purpose of this article is to explore the issues that the
      physical therapy profession needs to address as the rehabilitation management of
      the patient with critical illness evolves.

PMID- 23162042
TI  - The six-minute walk test in chronic pediatric conditions: a systematic review of
      measurement properties.
AB  - BACKGROUND: The Six-Minute Walk Test (6MWT) is increasingly being used as a
      functional outcome measure for chronic pediatric conditions. Knowledge about its
      measurement properties is needed to determine whether it is an appropriate test
      to use. PURPOSE: The purpose of this study was to systematically review all
      published clinimetric studies on the 6MWT in chronic pediatric conditions. DATA
      SOURCES: The databases MEDLINE, EMBASE, CINAHL, PEDro, and SPORTDiscus were
      searched up to February 2012. STUDY SELECTION: Studies designed to evaluate
      measurement properties of the 6MWT in a chronic pediatric condition were included
      in the systematic review. DATA EXTRACTION: The methodological quality of the
      included studies and the measurement properties of the 6MWT were examined. DATA
      SYNTHESIS: A best evidence synthesis was performed on 15 studies, including 9
      different chronic pediatric conditions. Limited evidence to strong evidence was
      found for reliability in various chronic conditions. Strong evidence was found
      for positive criterion validity of the 6MWT with peak oxygen uptake in some
      populations, but negative criterion validity was found in other populations.
      Construct validity remained unclear in most patient groups because of
      methodological flaws. Little evidence was available for responsiveness and
      measurement error. Studies showed large variability in test procedures despite
      existing guidelines for the performance of the 6MWT. LIMITATIONS: Unavailability
      of a specific checklist to evaluate the methodological quality of clinimetric
      studies on performance measures was a limitation of the study. CONCLUSIONS:
      Evidence for measurement properties of the 6MWT varies largely among chronic
      pediatric conditions. Further research is needed in all patient groups to explore
      the ability of the 6MWT to measure significant and clinically important changes.
      Until then, changes measured with the 6MWT should be interpreted with caution.
      Future studies or consensus regarding modified test procedures in the pediatric
      population is recommended.

PMID- 23162043
TI  - Sleep deprivation has no effect on dynamic visual acuity in military service
      members who are healthy.
AB  - BACKGROUND: The risk of traumatic brain injury (TBI) and comorbid posttraumatic
      dizziness is elevated in military operational environments. Sleep deprivation is
      known to affect a service member's performance while deployed, although little is
      known about its effects on vestibular function. Recent findings suggest that
      moderate acceleration step rotational stimuli may elicit a heightened angular
      vestibulo-ocular reflex (aVOR) response relative to low-frequency sinusoidal
      stimuli after 26 hours of sleep deprivation. There is concern that a sleep
      deprivation-mediated elevation in aVOR function could confound detection of
      comorbid vestibular pathology in service members with TBI. The term "dynamic
      visual acuity" (DVA) refers to an individual's ability to see clearly during head
      movement and is a behavioral measure of aVOR function. The Dynamic Visual Acuity
      Test (DVAT) assesses gaze instability by measuring the difference between head
      stationary and head-moving visual acuity. OBJECTIVE: The purpose of this study
      was to investigate the effects of 26 hours of sleep deprivation on DVA as a
      surrogate for aVOR function. DESIGN: This observational study utilized a repeated
      measures design. METHODS: Twenty soldiers with no history of vestibular insult or
      head trauma were assessed by means of the DVAT at angular head velocities of 120
      to 180 degrees /s. Active and passive yaw and pitch impulses were obtained before
      and after sleep deprivation. RESULTS: Yaw DVA remained unchanged as the result of
      sleep deprivation. Active pitch DVA diminished by -0.005 LogMAR (down) and -0.055
      LogMAR (up); passive pitch DVA was degraded by -0.06 LogMAR (down) and -0.045
      LogMAR (up). LIMITATIONS: Sample homogeneity largely confounded accurate
      assessment of test-retest reliability in this study, resulting in intraclass
      correlation coefficients lower than those previously reported. CONCLUSIONS:
      Dynamic visual acuity testing in soldiers who are healthy revealed no change in
      gaze stability after rapid yaw impulses and subclinical changes in pitch DVA
      after sleep deprivation. Findings suggest that DVA is not affected by short-term
      sleep deprivation under clinical conditions.

PMID- 23162044
TI  - Postdural puncture headache: Do not forget the children.

PMID- 23162045
TI  - Damage to white matter pathways in subacute and chronic spatial neglect: a group
      study and 2 single-case studies with complete virtual "in vivo" tractography
      dissection.
AB  - The exact anatomical localization of right hemisphere lesions that lead to left
      spatial neglect is still debated. The effect of confounding factors such as acute
      diaschisis and hypoperfusion, visual field defects, and lesion size may account
      for conflicting results that have been reported in the literature. Here, we
      present a comprehensive anatomical investigation of the gray- and white matter
      lesion correlates of left spatial neglect, which was run in a sample 58 patients
      with subacute or chronic vascular strokes in the territory of the right middle
      cerebral artery. Standard voxel-based correlates confirmed the role played by
      lesions in the posterior parietal cortex (supramarginal gyrus, angular gyrus, and
      temporal-parietal junction), in the frontal cortex (frontal eye field, middle and
      inferior frontal gyrus), and in the underlying parietal-frontal white matter.
      Using a new diffusion tensor imaging-based atlas of the human brain, we were able
      to run, for the first time, a detailed analysis of the lesion involvement of
      subcortical white matter pathways. The results of this analysis revealed that,
      among the different pathways linking parietal with frontal areas, damage to the
      second branch of the superior longitudinal fasciculus (SLF II) was the best
      predictor of left spatial neglect. The group study also revealed a subsample of
      patients with neglect due to focal lesion in the lateral-dorsal portion of the
      thalamus, which connects the premotor cortex with the inferior parietal lobule.
      The relevance of fronto-parietal disconnection was further supported by complete
      in vivo tractography dissection of white matter pathways in 2 patients, one with
      and the other without signs of neglect. These 2 patients were studied both in the
      acute phase and 1 year after stroke and were perfectly matched for age,
      handedness, stroke onset, lesion size, and for cortical lesion involvement. Taken
      together, the results of the present study support the hypothesis that anatomical
      disconnections leading to a functional breakdown of parietal-frontal networks are
      an important pathophysiological factor leading to chronic left spatial neglect.
      Here, we propose that different loci of SLF disconnection on the rostro-caudal
      axis can also be associated with disconnection of short-range white matter
      pathways within the frontal or parietal areas. Such different local disconnection
      patterns can play a role in the important clinical variability of the neglect
      syndrome. 

PMID- 23162046
TI  - Relating anatomical and social connectivity: white matter microstructure predicts
      emotional empathy.
AB  - Understanding cues to the internal states of others involves a widely distributed
      network of brain regions. Although white matter (WM) connections are likely
      crucial for communication between these regions, the role of anatomical
      connectivity in empathic processing remains unexplored. The present study tested
      for a relationship between anatomical connectivity and empathy by assessing the
      WM microstructural correlates of affective empathy, which promotes interpersonal
      understanding through emotional reactions, and cognitive empathy, which does so
      via perspective taking. Associations between fractional anisotropy (FA) and the
      emotional (empathic concern, EC) and cognitive (perspective taking, PT)
      dimensions of empathy as assessed by the Interpersonal Reactivity Index were
      examined. EC was positively associated with FA in tracts providing communicative
      pathways within the limbic system, between perception and action-related regions,
      and between perception and affect-related regions, independently of individual
      differences in age, gender, and other dimensions of interpersonal reactivity.
      These findings provide a neuroanatomical basis for the rapid, privileged
      processing of emotional sensory information and the automatic elicitation of
      responses to the affective displays of others. 

PMID- 23162048
TI  - Notice of retraction: 'The emergence of orthographic word representations in the
      brain: evaluating a neural shape-based framework using fMRI and the HMAX model'
      by Wouter Braet, Jonas Kubilius, Johan Wagemans and Hans P. Op de Beeck.
      doi:10.1093/Cercor/bhs355, published online November 16, 2012.

PMID- 23162049
TI  - The nutrition needs of low-income families regarding living healthier lifestyles:
      Findings from a qualitative study.
AB  - Pediatric obesity and nutrition-related problems continue to be problematic
      around the world. The purpose of the current qualitative study was to learn more
      about the barriers low-income, minority families face to healthy living and where
      they turn for health-related information. Five focus groups were conducted using
      open-ended standardized questions. Standardized transcript analysis and coding
      techniques were used to arrive at five saturated themes. The project was
      conducted in partnership with a community based Early/Head Start agency. Adult
      parents of preschool children were invited to participate. Results indicate that
      low-income minority families face many barriers to eating healthily: while
      families do eat some healthy foods, they also eat many unhealthy foods; they rely
      primarily on family members for their nutrition information; they have some
      desire to change their own health habits (but generally not those of their
      children); and they have inadequate nutritional knowledge. Options for better
      reaching this population with important health information are discussed. 

PMID- 23162050
TI  - Enhancing early attachment: Design and pilot study of an intervention for primary
      health care dyads.
AB  - The attachment style of an infant with his caregiver can greatly influence his
      future development. Many interventions have been proposed to enhance early secure
      attachment styles, but few have characteristics that make them suitable for
      primary health care. The objective of the study wasto design a complex
      intervention for promoting secure attachment in dyads detected in Primary Health
      Care with altered patterns of attachment styles. The methodology proposed by the
      UK Medical Research Council was used: (1) theoretical phase: literature review;
      (2) modelling phase: the main components of the intervention were defined through
      qualitative research; and (3) exploration phase: pilot study of the preliminary
      intervention. The attachment style of the dyads was evaluated using the Massie
      Campbell scale prior to and four months after the pilot intervention. The
      preliminary intervention was designed: a group workshop (five to seven dyads,
      with children aged between 6 and 12 months and two health care professional
      monitors) structured around various activities that specifically dealt with the
      skills associated with parental sensitivity and addressed relevant issues to
      child rearing. The intervention was then tested in a pilot study of 11 dyads in
      two primary health care centres. The analysis was done with nine dyads (two were
      lost in the second evaluation), and showed an improvement of 33 per cent in the
      secure attachment style in the dyads (not statistically significant). An original
      intervention is designed and proposed for dyads who have early indicators of
      altered styles of attachment in primary health care. 

PMID- 23162047
TI  - Methylphenidate enhances executive function and optimizes prefrontal function in
      both health and cocaine addiction.
AB  - Previous studies have suggested dopamine to be involved in error
      monitoring/processing, possibly through impact on reinforcement learning. The
      current study tested whether methylphenidate (MPH), an indirect dopamine agonist,
      modulates brain and behavioral responses to error, and whether such modulation is
      more pronounced in cocaine-addicted individuals, in whom dopamine
      neurotransmission is disrupted. After receiving oral MPH (20 mg) or placebo
      (counterbalanced), 15 healthy human volunteers and 16 cocaine-addicted
      individuals completed a task of executive function (the Stroop color word) during
      functional magnetic resonance imaging (fMRI). During MPH, despite not showing
      differences on percent accuracy and reaction time, all subjects committed fewer
      total errors and slowed down more after committing errors, suggestive of more
      careful responding. In parallel, during MPH all subjects showed reduced dorsal
      anterior cingulate cortex response to the fMRI contrast error>correct. In the
      cocaine subjects only, MPH also reduced error>correct activity in the
      dorsolateral prefrontal cortex (controls instead showed lower error>correct
      response in this region during placebo). Taken together, MPH modulated
      dopaminergically innervated prefrontal cortical areas involved in error-related
      processing, and such modulation was accentuated in the cocaine subjects. These
      results are consistent with a dopaminergic contribution to error-related
      processing during a cognitive control task. 

PMID- 23162052
TI  - NetCAD: a network analysis tool for coronary artery disease-associated PPI
      network.
AB  - SUMMARY: The systematic and unbiased charting of protein-protein interaction
      (PPI) networks relevant to health or diseases has become an important and
      burgeoning challenge in systems biology. Further, current reports have supported
      that good correlation exists between the topological properties and biological
      function of protein nodes in networks. Coronary artery disease (CAD, also called
      coronary heart disease) is the most common type of heart disease worldwide.
      Traditional approaches of studying individual gene or protein have shown their
      weakness in such complex disease. Here, we provide NetCAD, a web-based tool for
      systematic investigation of CAD-specific proteins in human PPI network. The
      features of NetCAD includes the following: proposing a novel method combining
      biological principles and graph theory, quantified topological analysis tools,
      build-in PPI information database consolidated from major public databases,
      creating CAD-associated subnetwork and visualizing network graph with good visual
      effects. NetCAD may provide important biological information for uncovering the
      molecular mechanisms and potential targets for therapies of CAD, which could not
      be found merely through molecular biology methods. AVAILABILITY AND
      IMPLEMENTATION: NetCAD is freely available at: http://www.herbbol.org/netcad/.
      CONTACT: zhliu@implad.ac.cn or zhliu.liulab@foxmail.com

PMID- 23162051
TI  - Moderating effects of gender on the relationship between poverty and children's
      externalizing behaviors.
AB  - Previous research suggests that boys are at a greater likelihood of exhibiting
      externalizing behaviors throughout their childhood than girls. In addition,
      previous research suggests that children who are born into impoverished
      conditions are more likely to exhibit externalizing behaviors than their peers
      who are born into higher socio-economic conditions. The purpose of this study was
      to investigate and compare the trajectory of externalizing behaviors between boys
      and girls. In addition, the effects of poverty on externalizing behaviors by
      gender were also investigated. The findings suggest that in the sample used for
      this study, boys and girls were virtually equal in externalizing behaviors from 2
      years old through 5th grade. In addition, analyses revealed that time spent in
      poverty predicted a greater occurrence of externalizing behaviors over time for
      girls, but not boys. These findings suggest that what has previously been assumed
      about externalizing behaviors in boys and girls may be less concrete than was
      once thought. Implications and future research directions are discussed. 

PMID- 23162053
TI  - PASS-bis: a bisulfite aligner suitable for whole methylome analysis of Illumina
      and SOLiD reads.
AB  - SUMMARY: The sequencing of bisulfite-treated DNA (Bi-Seq) is becoming a gold
      standard for methylation studies. The mapping of Bi-Seq reads is complex and
      requires special alignment algorithms. This problem is particularly relevant for
      SOLiD color space, where the bisulfite conversion C/T changes two adjacent colors
      into 16 possible combinations. Here, we present an algorithm that efficiently
      aligns Bi-Seq reads obtained either from SOLiD or Illumina. An accompanying
      methylation-caller program creates a genomic view of methylated and unmethylated
      Cs on both DNA strands. AVAILABILITY AND IMPLEMENTATION: The algorithm has been
      implemented as an option of the program PASS, freely available at
      http://pass.cribi.unipd.it. CONTACT: pass@cribi.unipd.it SUPPLEMENTARY
      INFORMATION: Supplementary data are available at Bioinformatics online.

PMID- 23162054
TI  - mzMatch-ISO: an R tool for the annotation and relative quantification of isotope
      labelled mass spectrometry data.
AB  - MOTIVATION: Stable isotope-labelling experiments have recently gained increasing
      popularity in metabolomics studies, providing unique insights into the dynamics
      of metabolic fluxes, beyond the steady-state information gathered by routine mass
      spectrometry. However, most liquid chromatography-mass spectrometry data analysis
      software lacks features that enable automated annotation and relative
      quantification of labelled metabolite peaks. Here, we describe mzMatch-ISO, a new
      extension to the metabolomics analysis pipeline mzMatch.R. RESULTS: Targeted and
      untargeted isotope profiling using mzMatch-ISO provides a convenient visual
      summary of the quality and quantity of labelling for every metabolite through
      four types of diagnostic plots that show (i) the chromatograms of the isotope
      peaks of each compound in each sample group; (ii) the ratio of mono-isotopic and
      labelled peaks indicating the fraction of labelling; (iii) the average peak area
      of mono-isotopic and labelled peaks in each sample group; and (iv) the trend in
      the relative amount of labelling in a predetermined isotopomer. To aid further
      statistical analyses, the values used for generating these plots are also
      provided as a tab-delimited file. We demonstrate the power and versatility of
      mzMatch-ISO by analysing a (13)C-labelled metabolome dataset from trypanosomal
      parasites. AVAILABILITY: mzMatch.R and mzMatch-ISO are available free of charge
      from http://mzmatch.sourceforge.net and can be used on Linux and Windows
      platforms running the latest version of R. CONTACT:
      rainer.breitling@manchester.ac.uk. SUPPLEMENTARY INFORMATION: Supplementary data
      are available at Bioinformatics online.

PMID- 23162055
TI  - Drug-target interaction prediction by learning from local information and
      neighbors.
AB  - MOTIVATION: In silico methods provide efficient ways to predict possible
      interactions between drugs and targets. Supervised learning approach, bipartite
      local model (BLM), has recently been shown to be effective in prediction of drug
      target interactions. However, for drug-candidate compounds or target-candidate
      proteins that currently have no known interactions available, its pure 'local'
      model is not able to be learned and hence BLM may fail to make correct prediction
      when involving such kind of new candidates. RESULTS: We present a simple
      procedure called neighbor-based interaction-profile inferring (NII) and integrate
      it into the existing BLM method to handle the new candidate problem.
      Specifically, the inferred interaction profile is treated as label information
      and is used for model learning of new candidates. This functionality is
      particularly important in practice to find targets for new drug-candidate
      compounds and identify targeting drugs for new target-candidate proteins.
      Consistent good performance of the new BLM-NII approach has been observed in the
      experiment for the prediction of interactions between drugs and four categories
      of target proteins. Especially for nuclear receptors, BLM-NII achieves the most
      significant improvement as this dataset contains many drugs/targets with no
      interactions in the cross-validation. This demonstrates the effectiveness of the
      NII strategy and also shows the great potential of BLM-NII for prediction of
      compound-protein interactions. CONTACT: jpmei@ntu.edu.sg SUPPLEMENTARY
      INFORMATION: Supplementary data are available at Bioinformatics online.

PMID- 23162056
TI  - DoseSim: a tool for pharmacokinetic/pharmacodynamic analysis and dose
      reconstruction.
AB  - Assessing and improving the safety of chemicals and the efficacy of drugs depends
      on an understanding of the biodistribution, clearance and biological effects of
      the chemical(s) of interest. A promising methodology for the prediction of these
      phenomena is physiologically based pharmacokinetic/pharmacodynamic modeling,
      which centers on the prediction of chemical absorption, distribution, metabolism
      and excretion (pharmacokinetics) and the biological effects (pharmacodynamics) of
      the chemical on the organism. Strengths of this methodology include modeling
      across multiple scales of biological organization and facilitate the
      extrapolation of results across routes of exposure, dosing levels and species. It
      is also useful as the foundation for tools to (i) predict biomarker levels
      (concentrations of chemical species found in the body that indicate exposure to a
      foreign chemical), given a chemical dose or exposure; (ii) reconstruct a dose,
      given the levels of relevant biomarkers; and (iii) estimate population
      variability. Despite the importance and promise of physiologically based
      pharmacokinetic /pharmacodynamics-based approaches to forward and reverse
      dosimetry, there is currently a lack of user-friendly, freely available
      implementations that are accessible and useful to a broad range of users. DoseSim
      was developed to begin to fill this gap. AVAILABILITY: The application is
      available under the GNU General Public License from
      http://scb.colostate.edu/dosesim.html.

PMID- 23162057
TI  - Largenet2: an object-oriented programming library for simulating large adaptive
      networks.
AB  - SUMMARY: The largenet2 C++ library provides an infrastructure for the simulation
      of large dynamic and adaptive networks with discrete node and link states.
      AVAILABILITY: The library is released as free software. It is available at
      http://biond.github.com/largenet2. Largenet2 is licensed under the Creative
      Commons Attribution-NonCommercial 3.0 Unported License. CONTACT: gerd@biond.org

PMID- 23162058
TI  - VirusSeq: software to identify viruses and their integration sites using next
      generation sequencing of human cancer tissue.
AB  - SUMMARY: We developed a new algorithmic method, VirusSeq, for detecting known
      viruses and their integration sites in the human genome using next-generation
      sequencing data. We evaluated VirusSeq on whole-transcriptome sequencing (RNA
      Seq) data of 256 human cancer samples from The Cancer Genome Atlas. Using these
      data, we showed that VirusSeq accurately detects the known viruses and their
      integration sites with high sensitivity and specificity. VirusSeq can also
      perform this function using whole-genome sequencing data of human tissue.
      AVAILABILITY: VirusSeq has been implemented in PERL and is available at
      http://odin.mdacc.tmc.edu/~xsu1/VirusSeq.html. CONTACT: xsu1@mdanderson.org
      SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics
      online.

PMID- 23162059
TI  - VAGUE: a graphical user interface for the Velvet assembler.
AB  - SUMMARY: Velvet is a popular open-source de novo genome assembly software tool,
      which is run from the Unix command line. Most of the problems experienced by new
      users of Velvet revolve around constructing syntactically and semantically
      correct command lines, getting input files into acceptable formats and assessing
      the output. Here, we present Velvet Assembler Graphical User Environment (VAGUE),
      a multi-platform graphical front-end for Velvet. VAGUE aims to make sequence
      assembly accessible to a wider audience and to facilitate better usage amongst
      existing users of Velvet. AVAILABILITY AND IMPLEMENTATION: VAGUE is implemented
      in JRuby and targets the Java Virtual Machine. It is available under an open
      source GPLv2 licence from http://www.vicbioinformatics.com/. CONTACT:
      torsten.seemann@monash.edu.

PMID- 23162061
TI  - Ward nurses' resuscitation of critical patients: current training and barriers.
AB  - Little is known about the current training and barriers in resuscitation skills
      among practicing ward nurses. A convenience sample of 459 ward nurses, recruited
      from 11 academic teaching hospitals in Korea, were surveyed to assess current
      training and barriers to optimal resuscitation performance on the wards. The
      Perceived Barriers scale was developed, refined, and its psychometric properties
      were assessed. Approximately 36% of nurses had received simulation-based
      resuscitation skills training. Exploratory factor analysis identified four
      barriers accounting for 58.4% of the variance: insufficient training (37.7%),
      lack of competence (9.8%), lack of self-confidence (5.9%), and workload and
      tension (5.1%). Strategic planning and resuscitation skills training should be
      incorporated into staff development programs to reduce barriers to optimal
      resuscitation performance and cope with work demands for ward nurses. 

PMID- 23162062
TI  - Effect of aging on coordinated eye and hand movements with two-segment sequence.
AB  - This study examined how aging compromises coordinative eye-hand movements with
      multiple segments. Older adults and young controls performed two-segment
      movements with the eyes only or with the eyes and hand together. The results
      showed minimal age-related changes on the initiation and execution of primary
      saccade during the first segment. However, the older adults showed a scaling
      problem of saccade velocity when hand movements were included. They were also
      slow in stabilizing gaze fixation to the first target. Regarding hand movements,
      the older adults pronouncedly increased the deceleration phase compared with the
      controls while fixating their gazes to the target. They also increased the
      intersegment interval for both eye and hand movements. Taken together, aging
      differentially affects various components of movements, which contributes to the
      slowness of overall performance.

PMID- 23162060
TI  - Impaired response to exercise intervention in the vasculature in metabolic
      syndrome.
AB  - Physical activity decreases risk for diabetes and cardiovascular disease
      morbidity and mortality; however, the specific impact of exercise on the diabetic
      vasculature is unexamined. We hypothesized that an acute, moderate exercise
      intervention in diabetic and hypertensive rats would induce mitochondrial
      biogenesis and mitochondrial antioxidant defence to improve vascular resilience.
      SHHF/Mcc-fa(cp) lean (hypertensive) and obese (hypertensive, insulin resistant),
      as well as Sprague Dawley (SD) control rats were run on a treadmill for 8 days.
      In aortic lysates from SD rats, we observed a significant increase in subunit
      proteins from oxidative phosphorylation (OxPhos) complexes I-III, with no changes
      in the lean or obese SHHF rats. Exercise also increased the expression of
      mitochondrial antioxidant defence uncoupling protein 3 (UCP3) (p < 0.05) in SHHF
      lean rats, whereas no changes were observed in the SD or SHHF obese rats with
      exercise. We evaluated upstream signalling pathways for mitochondrial biogenesis,
      and only peroxisome proliferators-activated receptor gamma coactivator 1alpha
      (PGC-1alpha) significantly decreased in SHHF lean rats (p < 0.05) with exercise.
      In these experiments, we demonstrate absent mitochondrial induction with exercise
      exposure in models of chronic vascular disease. These findings suggest that
      chronic vascular stress results in decreased sensitivity of vasculature to the
      adaptive mitochondrial responses normally induced by exercise.

PMID- 23162063
TI  - Influence of vestibular afferent input on common modulation of human soleus motor
      units during standing.
AB  - The purpose of this study was to investigate whether application of bipolar
      galvanic vestibular stimulation (GVS) would influence the common modulation of
      motor unit discharge rate in bilateral soleus muscles during quiet standing.
      Soleus motor unit activity was recorded with fine wire electrodes in each leg.
      Subjects stood, with eyes closed, on two adjacent force platforms to record
      postural sway with the head facing straight ahead, turned to right, or turned
      left. Subjects also swayed voluntarily without GVS to the same position as evoked
      during the GVS. There was no difference in the common drive to bilateral soleus
      motoneurons during quiet standing and voluntary sway tasks. Common drive was
      significantly lower during right cathode GVS with the head straight or turned to
      the right. These results demonstrate that manipulation of vestibular afferent
      input influences the common modulation of bilateral soleus motor unit pairs
      during quiet standing.

PMID- 23162065
TI  - Optic flow contribution to locomotion adjustments in obstacle avoidance.
AB  - Locomotion generates a visual movement pattern characterized as optic flow. To
      explore how the locomotor adjustments are affected by this pattern, an
      experimental paradigm was developed to eliminate optic flow during obstacle
      avoidance. The aim was to investigate the contribution of optic flow in obstacle
      avoidance by using a stroboscopic lamp. Ten young adults walked on an 8m pathway
      and stepped over obstacles at two heights. Visual sampling was determined by a
      stroboscopic lamp (static and dynamic visual sampling). Three-dimensional
      kinematics data showed that the visual information about self-motion provided by
      the optic flow was crucial for estimating the distance from and the height of the
      obstacle. Participants presented conservative behavior for obstacle avoidance
      under experimental visual sampling conditions, which suggests that optic flow
      favors the coupling of vision to adaptive behavior for obstacle avoidance.

PMID- 23162066
TI  - Development of temporal and spatial bimanual coordination during childhood.
AB  - Developmental changes in bimanual coordination were examined in four age groups:
      6/7, 10/11, 14/15 years, and young adults. Temporal coupling was assessed through
      the stabilizing contributions of interlimb interactions related to planning,
      error correction, and reflexes during rhythmic wrist movements, by comparing
      various unimanual and bimanual tasks involving passive and active movements.
      Spatial coupling was assessed via bimanual line-circle drawing. With increasing
      age, temporal stability improved. Relative contributions of planning and reflex
      interactions to the achieved stability did not change, whereas error correction
      improved. In-phase and antiphase coordination developed at similar rates;
      implications of this result were discussed in terms of mirror-activity
      inhibition. Overall spatial drawing performance (circularity, variability,
      smoothness) improved with age, and spatial interference was smaller in adults
      than children. Whereas temporal coupling increased from 6/7 years to adulthood,
      spatial coupling changed mainly after 14/15 years. This difference in the
      development of temporal and spatial coupling corresponds to the anterior
      posterior direction of corpus callosum myelination as reported in the literature.

PMID- 23162067
TI  - Sensorimotor control in overarm throwing.
AB  - Goal-directed movement is possible because the cortical regions regulating
      movement have continuous access to visual information. Extensive research from
      the various domains of motor control (i.e., neurophysiology, neuropsychology, and
      psychophysics) has documented the extent to which the unremitting availability of
      visual information enables the sensorimotor system to facilitate online control
      of goal-directed limb movement. However, the control mechanism guiding
      appreciably more complex movements characterized by ballistic, whole-body
      coordination is not well understood. In the overarm throw, for example, joint
      rotations must be optimally timed between body segments to exploit the passive
      flow of kinetic energy and, in turn, maximize projectile speed while maintaining
      accuracy. The purpose of this review is to draw from the various research domains
      in motor control and speculate on the nature of the sensorimotor control
      mechanism facilitating overarm throwing performance.

PMID- 23162068
TI  - Effect of fatigue on grip force control during object manipulation in carpal
      tunnel syndrome.
AB  - Eight subjects with carpal tunnel syndrome (CTS) (47.13 +/- 7.83 years) and 8
      matched controls (46.29 +/- 7.27 years) manipulated a test object fitted with an
      accelerometer and force sensor, both before and after hand muscle fatigue. Grip
      force and object acceleration were recorded and used to calculate grip force
      control variables that included Grip Force Peak, Safety Margin, and Time to Grip
      Force Peak. Individuals with CTS exhibited a higher Safety Margin (p = .010) and
      longer Time to Peak of Grip Force (p = .012) than healthy controls during object
      manipulation. Once fatigued, both groups significantly decreased their grip force
      to perform the task (Grip Force Peak; p = .017 and Safety Margin; p < .001).
      Nevertheless, individuals with CTS maintained an unnecessarily high safety
      margin. Our results suggest that CTS can adversely affect how the central nervous
      system regulates grip force, which might aggravate the inflammatory process and
      exacerbate the symptoms of this disease.

PMID- 23162069
TI  - Guanidine hydrochloride-induced alkali molten globule model of horse
      ferrocytochrome c.
AB  - This article compares structural, kinetic and thermodynamic properties of
      previously unknown guanidine hydrochloride (GdnHCl)-induced alkali molten globule
      (MG) state of horse 'ferrocytochrome c' (ferrocyt c) with the known NaCl-induced
      alkali-MG state of ferrocyt c. It is well known that Cl(-) arising from GdnHCl
      refolds and stabilizes the acid-denatured protein to MG state. We demonstrate
      that the GdnH(+) arising from GdnHCl (<=0.2 M) also transforms the base-denatured
      CO-liganded ferrocyt c (carbonmonoxycyt c) to MG state by making the
      electrostatic interactions to the negative charges of the protein. Structural and
      molecular properties extracted from the basic spectroscopic (circular dichroism
      (CD), fluorescence, FTIR and NMR) experiments suggest that the GdnH(+)- and Na(+)
      induced MG states of base-denatured carbonmonoxycyt c are molecular compact
      states containing native-like secondary structures and disordered tertiary
      structures. Kinetic experiments involving the measurement of the CO association
      to the alkaline ferrocyt c in the presence of different GdnHCl and NaCl
      concentrations indicate that the Na(+)-induced MG state is more constrained
      relative to that of GdnH(+)-induced MG state. Analyses of thermal (near UV-CD)
      denaturation curves of the base-denatured protein in the presence of different
      GdnHCl and NaCl concentration also indicate that the Na(+)-induced MG state is
      thermally more stable than the GdnH(+)-induced MG state.

PMID- 23162070
TI  - The CBL-interacting protein kinase CIPK26 is a novel interactor of Arabidopsis
      NADPH oxidase AtRbohF that negatively modulates its ROS-producing activity in a
      heterologous expression system.
AB  - The plant NADPH oxidases, known as respiratory burst oxidase homologues (Rbohs),
      play an indispensable role in a wide array of cellular and developmental
      processes. Arabidopsis thaliana RbohF (AtRbohF)-mediated production of reactive
      oxygen species (ROS) is involved in biotic and abiotic stress responses. Because
      of the toxicity of excess amount of ROS, the ROS-producing activity of Rbohs is
      speculated to be negatively regulated. However, its mechanism is mostly unknown
      to date. Here, we report the identification of calcineurin B-like protein
      interacting protein kinase 26 (CIPK26) as a novel regulatory factor of AtRbohF.
      We isolated CIPK26 as an AtRbohF-interacting partner by a yeast two-hybrid
      screen. Our co-immunoprecipitation assay revealed that the CIPK26 protein
      interacts with the N-terminal region of AtRbohF in Nicotiana benthamiana cell
      extracts. The fluorescence of both GFP-tagged CIPK26 and AtRbohF was
      predominantly observed at the cell periphery. We also showed that co-expression
      of CIPK26 decreases the ROS-producing activity of AtRbohF in HEK293T cells.
      Together, these results suggest that the direct binding of CIPK26 to AtRbohF
      negatively modulates ROS production and play a role in the regulation of ROS
      signalling in plants.

PMID- 23162071
TI  - The CompHP core competencies framework for health promotion in Europe.
AB  - BACKGROUND: The CompHP Project on Developing Competencies and Professional
      Standards for Health Promotion in Europe was developed in response to the need
      for new and changing health promotion competencies to address health challenges.
      This article presents the process of developing the CompHP Core Competencies
      Framework for Health Promotion across the European Union Member States and
      Candidate Countries. METHOD: A phased, multiple-method approach was employed to
      facilitate a consensus-building process on the development of the core
      competencies. Key stakeholders in European health promotion were engaged in a
      layered consultation process using the Delphi technique, online consultations,
      workshops, and focus groups. FINDINGS: Based on an extensive literature review, a
      mapping process was used to identify the core domains, which informed the first
      draft of the Framework. A consultation process involving two rounds of a Delphi
      survey with national experts in health promotion from 30 countries was carried
      out. In addition, feedback was received from 25 health promotion leaders who
      participated in two focus groups at a pan-European level and 116 health promotion
      practitioners who engaged in four country-specific consultations. A further 54
      respondents replied to online consultations, and there were a number of followers
      on various social media platforms. Based on four rounds of redrafting, the final
      Framework document was produced, consisting of 11 core domains and 68 core
      competency statements. CONCLUSIONS: The CompHP Core Competencies Framework for
      Health Promotion provides a resource for workforce development in Europe, by
      articulating the necessary knowledge, skills, and abilities that are required for
      effective practice. The core domains are based on the multidisciplinary concepts,
      theories, and research that make health promotion distinctive. It is the combined
      application of all the domains, the knowledge base, and the ethical values that
      constitute the CompHP Core Competencies Framework for Health Promotion.

PMID- 23162072
TI  - Developing consensus on the CompHP professional standards for health promotion in
      Europe.
AB  - Building on the CompHP Core Competencies for health promotion the Professional
      Standards for Health Promotion have been developed and consulted on across
      Europe. The standards were formulated to fit within the complexity of
      professional, occupational and educational standards frameworks in Europe as
      learning outcome standards with performance criteria, following the approach of
      the European Qualifications Framework. Three phases of consultation included an
      electronic consultation survey, focus groups and workshops, and an online
      consultation. The standards were revised at each stage following comments
      received. Responses from across Europe and beyond indicate high levels of
      agreement with the standards and support for their implementation in education
      and employment settings to accredit health promotion practitioners and raise the
      profile of health promotion in Europe.

PMID- 23162073
TI  - Using an experience documentation opportunity to certify advanced-level health
      education specialists.
AB  - The worldwide burden of diseases, environmental threats, and injuries help
      establish the global context and need for credentialing in health education and
      promotion. To ensure effective practice by certified or credentialed individuals,
      it is critical that the global health education and promotion workforce identify,
      agree on, and establish core competencies grounded in knowledge, skills, and
      abilities to strengthen the global capacity to improve the practice of health
      education at the entry and advanced levels. Dialog regarding the development of
      Domains of Core Competency for global capacity in health promotion has occurred.
      One unique process for granting certification was how a U.S. certifying
      organization used an Experience Documentation Opportunity to validate advanced
      level professional competency. In this article, a one-time, 6-month opportunity
      in certifying advanced-level health education specialists is documented, and the
      implications of these results on the Domains of Core Competency are discussed.
      The authors provide valuable insight for health education professionals worldwide
      on establishing a process for quality assurance and accountability and alignment
      with the current global competency discussion. The Experience Documentation
      Opportunity process also may be useful in international efforts to establish
      certification based on core competencies.

PMID- 23162074
TI  - Metastatic biomarker discovery through proteomics.
AB  - Tumor heterogeneity has been a stumbling block in the development of effective
      cancer treatments. Personalized medicine has evolved with the theory that
      matching therapies with the unique misregulated pathways often present in tumors
      will increase patient prognosis. Of particular interest is prediction or
      determination of the metastatic potential of a tumor. Thus, biomarkers that can
      predict metastases represent an enormous advance to our understanding over the
      clinical treatment of cancer. Considerable effort has been expended to
      characterize the cancer proteome for early detection, however, fewer efforts have
      been made to develop biomarkers to distinguish the potential for and the nature
      of metastasis. In this review, we discuss proteomic technologies as well as
      existing potential metastatic biomarkers for various cancers. In the conclusion,
      we discuss forward thinking as to what the field needs to enable translation to
      the clinic.

PMID- 23162075
TI  - Genetically engineered fusion proteins for treatment of cancer.
AB  - In this review, we summarize approaches to treat cancer with genetically
      engineered fusion proteins. Such proteins can act as decoy receptors for several
      ligands or as recruiters of immune effector cells to tumor. Examples of
      interference with growth factor-mediated tumor growth and tumor-related
      angiogenesis with fusion proteins consisting of the extracellular domains, and in
      some cases also of entities of one or several receptors and the Fc part of human
      IgG1, are discussed. In addition, we present strategies for recruitment of immune
      effector cells to tumor with fusion proteins. This can be achieved with fusion
      proteins consisting of a tumor-related antibody and a cytokine or major
      histocompatibilty complex class-I-peptide complexes, by T-cell receptor cytokine
      fusion proteins or by combination of a T-cell-recruiting antibody with a tumor
      related ligand or a defined T-cell receptor.

PMID- 23162077
TI  - Evidence of an autocrine role for leptin and leptin receptor in human breast
      cancer.
AB  - We studied potential associations between the expression of leptin, leptin
      receptor (LEPR) and clinicopathological parameters of breast cancer, and the
      correlation of leptin with human telomerase reverse transcriptase (hTERT) and
      cyclooxygenase 2 (COX2) PATIENTS AND METHODS: A total of 153 specimens were
      studied. Transcript levels were determined using quantitative polymerase chain
      reaction (qPCR), and were correlated with clinicopathological data collected for
      over 10 years. Additionally, leptin and LEPR expression was studied in several
      breast cell lines. RESULTS: Both leptin and LEPR mRNA expression were higher in
      malignant samples (p=0.0011 and 0.0014 respectively). Both were also expressed in
      MDA436 and MCF7 cell lines. Leptin showed a significant correlation with LEPR
      (r=0.504, p=0.0000000222). Leptin did not correlate significantly with clinical
      stage, tumour grade, or with the expression of hTERT or COX2. CONCLUSIONS: This
      study demonstrates that leptin and LEPR are more readily expressed in cancerous
      tissues suggesting a possible autocrine role in mammary carcinogenesis, which may
      be independent of hTERT and COX2 genes.

PMID- 23162076
TI  - Cancer metabolism: what we can learn from proteomic analysis by mass
      spectrometry.
AB  - A variety of genomic and proteomic tools have been used to study cancer
      metabolism and metabolomics in order to understand how cancer cells survive in
      their environment. Throughout the past decade, mass spectrometry has been
      routinely used for large-scale protein identification of complex biological
      mixtures. In this review, we discuss some recent developments in cancer
      metabolism by proteomic analysis using mass spectrometric techniques, focusing on
      pyruvate kinase, L-lactate dehydrogenase, Warburg effect, glutamine metabolism
      and oxidative stress.

PMID- 23162078
TI  - Unifying the genomics-based classes of cancer fusion gene partners: large cancer
      fusion genes are evolutionarily conserved.
AB  - BACKGROUND: Genes that fuse to cause cancer have been studied to determine
      molecular bases for proliferation, to develop diagnostic tools, and as targets
      for drugs. To facilitate identification of additional, cancer fusion genes,
      following observation of a chromosomal translocation, we have characterized the
      genomic features of the fusion gene partners. Previous work indicated that cancer
      fusion gene partners, are either large or evolutionarily conserved in comparison
      to the neighboring genes in the region of a chromosomal translocation. These
      results raised the question of whether large cancer fusion gene partners were
      also evolutionarily conserved. METHODS AND RESULTS: We developed two methods for
      quantifying evolutionary conservation values, allowing the conclusion that both
      large and small cancer fusion gene partners are more evolutionarily conserved
      than their neighbors. Additionally, we determined that cancer fusion gene
      partners have more 3' untranslated region secondary structures than do their
      neighbors. CONCLUSION: Coupled with previous algorithms, with or without
      transcriptome approaches, we expect these results to assist in the rapid and
      efficient use of chromosomal translocations to identify cancer fusion genes. The
      above parameters for any gene of interest can be accessed at
      www.cancerfusiongenes.com.

PMID- 23162082
TI  - Stability analysis of phylogenetic trees.
AB  - MOTIVATION: Phylogenetics, or reconstructing the evolutionary relationships of
      organisms, is critical for understanding evolution. A large number of heuristic
      algorithms for phylogenetics have been developed, some of which enable estimates
      of trees with tens of thousands of taxa. Such trees may not be robust, as small
      changes in the input data can cause major differences in the optimal topology.
      Tools that can assess the quality and stability of phylogenetic tree estimates
      and identify the most reliable parts of the tree are needed. RESULTS: We define
      measures that assess the stability of trees, subtrees and individual taxa with
      respect to changes in the input sequences. Our measures consider changes at the
      finest granularity in the input data (i.e. individual nucleotides). We
      demonstrate the effectiveness of our measures on large published datasets. Our
      measures are computationally feasible for phylogenetic datasets consisting of
      tens of thousands of taxa. AVAILABILITY: This software is available at
      http://bioinformatics.cise.ufl.edu/phylostab CONTACT: sheikh@cise.ufl.edu

PMID- 23162081
TI  - A system for exact and approximate genetic linkage analysis of SNP data in large
      pedigrees.
AB  - MOTIVATION: The use of dense single nucleotide polymorphism (SNP) data in genetic
      linkage analysis of large pedigrees is impeded by significant technical,
      methodological and computational challenges. Here we describe Superlink-Online
      SNP, a new powerful online system that streamlines the linkage analysis of SNP
      data. It features a fully integrated flexible processing workflow comprising both
      well-known and novel data analysis tools, including SNP clustering, erroneous
      data filtering, exact and approximate LOD calculations and maximum-likelihood
      haplotyping. The system draws its power from thousands of CPUs, performing data
      analysis tasks orders of magnitude faster than a single computer. By providing an
      intuitive interface to sophisticated state-of-the-art analysis tools coupled with
      high computing capacity, Superlink-Online SNP helps geneticists unleash the
      potential of SNP data for detecting disease genes. RESULTS: Computations
      performed by Superlink-Online SNP are automatically parallelized using novel
      paradigms, and executed on unlimited number of private or public CPUs. One novel
      service is large-scale approximate Markov Chain-Monte Carlo (MCMC) analysis. The
      accuracy of the results is reliably estimated by running the same computation on
      multiple CPUs and evaluating the Gelman-Rubin Score to set aside unreliable
      results. Another service within the workflow is a novel parallelized exact
      algorithm for inferring maximum-likelihood haplotyping. The reported system
      enables genetic analyses that were previously infeasible. We demonstrate the
      system capabilities through a study of a large complex pedigree affected with
      metabolic syndrome. AVAILABILITY: Superlink-Online SNP is freely available for
      researchers at http://cbl-hap.cs.technion.ac.il/superlink-snp. The system source
      code can also be downloaded from the system website. CONTACT:
      omerw@cs.technion.ac.il SUPPLEMENTARY INFORMATION: Supplementary data are
      available at Bioinformatics online.

PMID- 23162083
TI  - PTID: an integrated web resource and computational tool for agrochemical
      discovery.
AB  - SUMMARY: Although in silico drug discovery approaches are crucial for the
      development of pharmaceuticals, their potential advantages in agrochemical
      industry have not been realized. The challenge for computer-aided methods in
      agrochemical arena is a lack of sufficient information for both pesticides and
      their targets. Therefore, it is important to establish such knowledge repertoire
      that contains comprehensive pesticides' profiles, which include physicochemical
      properties, environmental fates, toxicities and mode of actions. Here, we present
      an integrated platform called Pesticide-Target interaction database (PTID), which
      comprises a total of 1347 pesticides with rich annotation of ecotoxicological and
      toxicological data as well as 13 738 interactions of pesticide-target and 4245
      protein terms via text mining. Additionally, through the integration of
      ChemMapper, an in-house computational approach to polypharmacology, PTID can be
      used as a computational platform to identify pesticides targets and design novel
      agrochemical products. AVAILABILITY: http://lilab.ecust.edu.cn/ptid/. CONTACT:
      hlli@ecust.edu.cn; xhqian@ecust.edu.cn SUPPLEMENTARY INFORMATION: Supplementary
      data are available at Bioinformatics online.

PMID- 23162084
TI  - An application of a relational database system for high-throughput prediction of
      elemental compositions from accurate mass values.
AB  - SUMMARY: High-accuracy mass values detected by high-resolution mass spectrometry
      analysis enable prediction of elemental compositions, and thus are used for
      metabolite annotations in metabolomic studies. Here, we report an application of
      a relational database to significantly improve the rate of elemental composition
      predictions. By searching a database of pre-calculated elemental compositions
      with fixed kinds and numbers of atoms, the approach eliminates redundant
      evaluations of the same formula that occur in repeated calculations with other
      tools. When our approach is compared with HR2, which is one of the fastest tools
      available, our database search times were at least 109 times shorter than those
      of HR2. When a solid-state drive (SSD) was applied, the search time was 488 times
      shorter at 5 ppm mass tolerance and 1833 times at 0.1 ppm. Even if the search by
      HR2 was performed with 8 threads in a high-spec Windows 7 PC, the database search
      times were at least 26 and 115 times shorter without and with the SSD. These
      improvements were enhanced in a low spec Windows XP PC. We constructed a web
      service 'MFSearcher' to query the database in a RESTful manner. AVAILABILITY AND
      IMPLEMENTATION: Available for free at http://webs2.kazusa.or.jp/mfsearcher. The
      web service is implemented in Java, MySQL, Apache and Tomcat, with all major
      browsers supported. CONTACT: sakurai@kazusa.or.jp SUPPLEMENTARY INFORMATION:
      Supplementary data are available at Bioinformatics online.

PMID- 23162085
TI  - Bridging the scales: semantic integration of quantitative SBML in graphical multi
      cellular models and simulations with EPISIM and COPASI.
AB  - MOTIVATION: Biological reality can in silico only be comprehensively represented
      in multi-scaled models. To this end, cell behavioural models addressing the multi
      cellular level have to be semantically linked with mechanistic molecular models.
      These requirements have to be met by flexible software workflows solving the
      issues of different time scales, inter-model variable referencing and flexible
      sub-model embedding. RESULTS: We developed a novel software workflow (EPISIM) for
      the semantic integration of Systems Biology Markup Language (SBML)-based
      quantitative models in multi-scaled tissue models and simulations. This workflow
      allows to import and access SBML-based models. SBML model species, reactions and
      parameters are semantically integrated in cell behavioural models (CBM)
      represented by graphical process diagrams. By this, cellular states like
      proliferation and differentiation can be flexibly linked to gene-regulatory or
      biochemical reaction networks. For a multi-scale agent-based tissue simulation
      executable code is automatically generated where different time scales of
      imported SBML models and CBM have been mapped. We demonstrate the capabilities of
      the novel software workflow by integrating Tyson's cell cycle model in our model
      of human epidermal tissue homeostasis. Finally, we show the semantic interplay of
      the different biological scales during tissue simulation. AVAILABILITY: The
      EPISIM platform is available as binary executables for Windows, Linux and Mac OS
      X at http://www.tiga.uni-hd.de. Supplementary data are available at
      http://www.tiga.uni-hd.de/supplements/SemSBMLIntegration.html. CONTACT:
      niels.grabe@bioquant.uni-heidelberg.de.

PMID- 23162086
TI  - Visualization and Phospholipid Identification (VaLID): online integrated search
      engine capable of identifying and visualizing glycerophospholipids with given
      mass.
AB  - MOTIVATION: Establishing phospholipid identities in large lipidomic datasets is a
      labour-intensive process. Where genomics and proteomics capitalize on sequence
      based signatures, glycerophospholipids lack easily definable molecular
      fingerprints. Carbon chain length, degree of unsaturation, linkage, and polar
      head group identity must be calculated from mass to charge (m/z) ratios under
      defined mass spectrometry (MS) conditions. Given increasing MS sensitivity, many
      m/z values are not represented in existing prediction engines. To address this
      need, Visualization and Phospholipid Identification is a web-based application
      that returns all theoretically possible phospholipids for any m/z value and MS
      condition. Visualization algorithms produce multiple chemical structure files for
      each species. Curated lipids detected by the Canadian Institutes of Health
      Research Training Program in Neurodegenerative Lipidomics are provided as high
      resolution structures. AVAILABILITY: VaLID is available through the Canadian
      Institutes of Health Research Training Program in Neurodegenerative Lipidomics
      resources web site at https://www.med.uottawa.ca/lipidomics/resources.html.
      CONTACTS: lipawrd@uottawa.ca SUPPLEMENTARY INFORMATION: Supplementary data are
      available at Bioinformatics online.

PMID- 23162088
TI  - Modulation of sensory irritation responsiveness by adenosine and malodorants.
AB  - Respiratory tract reflex responses are an important defense mechanism against
      noxious airborne materials. This study was aimed at defining the effects of
      adenosine on sensory irritation responsiveness and its role in odorant-irritant
      interactions. These experiments were aimed at testing the hypothesis that
      adenosine, through the A2 receptor, enhances trigeminal nerve responses to
      multiple irritants and that odorants enhance responsiveness to irritants through
      A2 pathways in the female C57Bl/6 mouse. The adenosine precursor, AMP,
      immediately and markedly increased the sensory irritation response to capsaicin,
      cyclohexanone, and styrene, irritants that activate chemosensory nerves through
      differing receptor pathways. The neuromodulatory effect was blocked by the
      general adenosine receptor antagonist theophylline and by the A2 receptor
      specific antagonist DMPX. Multiple odorants were examined, including R-carvone
      (spearmint), linalool (lavender), trimethylamine (rotting fish), mercaptoethanol,
      and ethyl sulfide (stench and rotten eggs). Of these, only mercaptoethanol and
      ethyl sulfide exhibited neuromodulatory effects, enhancing the sensory irritation
      response to styrene or cyclohexanone. This effect was blocked by theophylline and
      DMPX indicating the importance of adenosine A2 receptor pathways in this effect.
      These results highlight that trigeminal chemosensory responsiveness is not
      static, but can be quickly modulated by adenosine and select odors resulting in
      hyperresponsive states.

PMID- 23162087
TI  - Scaffolding low quality genomes using orthologous protein sequences.
AB  - MOTIVATION: The ready availability of next-generation sequencing has led to a
      situation where it is easy to produce very fragmentary genome assemblies. We
      present a pipeline, SWiPS (Scaffolding With Protein Sequences), that uses
      orthologous proteins to improve low quality genome assemblies. The protein
      sequences are used as guides to scaffold existing contigs, while simultaneously
      allowing the gene structure to be predicted by homology. RESULTS: To perform,
      SWiPS does not depend on a high N50 or whole proteins being encoded on a single
      contig. We tested our algorithm on simulated next-generation data from Ciona
      intestinalis, real next-generation data from Drosophila melanogaster, a complex
      genome assembly of Homo sapiens and the low coverage Sanger sequence assembly of
      Callorhinchus milii. The improvements in N50 are of the order of ~20% for the
      C.intestinalis and H.sapiens assemblies, which is significant, considering the
      large size of intergenic regions in these eukaryotes. Using the CEGMA pipeline to
      assess the gene space represented in the genome assemblies, the number of genes
      retrieved increased by >110% for C.milii and from 20 to 40% for C.intestinalis.
      The scaffold error rates are low: 85-90% of scaffolds are fully correct, and >95%
      of local contig joins are correct. AVAILABILITY: SWiPS is available freely for
      download at http://www.well.ox.ac.uk/~yli142/swips.html. CONTACT:
      yang.li@well.ox.ac.uk or copley@well.ox.ac.uk

PMID- 23162090
TI  - Accelerated failure time models for censored survival data under referral bias.
AB  - The estimation of progression to liver cirrhosis and identifying its risk factors
      are often of epidemiological interest in hepatitis C natural history study. In
      most hepatitis C cohort studies, patients were usually recruited to the cohort
      with a referral bias because clinically the patients with more rapid disease
      progression were preferentially referred to liver clinics. A pair of correlated
      event times may be observed for each patient, time to development of cirrhosis
      and time to referral to a cohort. This paper considers accelerated failure time
      models to study the effects of covariates on progression to cirrhosis. A new non
      parametric estimator is proposed to handle a flexible bivariate distribution of
      the cirrhosis and referral times and to take the referral bias into account. The
      asymptotic normality of the proposed estimator is also provided. Numerical
      studies show that the coefficient estimator and its covariance function estimator
      perform well.

PMID- 23162091
TI  - Mitotane therapy in adrenocortical cancer induces CYP3A4 and inhibits 5alpha
      reductase, explaining the need for personalized glucocorticoid and androgen
      replacement.
AB  - CONTEXT: Mitotane [1-(2-chlorophenyl)-1-(4-chlorophenyl)-2,2-dichloroethane] is
      the first-line treatment for metastatic adrenocortical carcinoma (ACC) and is
      also regularly used in the adjuvant setting after presumed complete removal of
      the primary tumor. Mitotane is considered an adrenolytic substance, but there is
      limited information on distinct effects on steroidogenesis. However, adrenal
      insufficiency and male hypogonadism are widely recognized side effects of
      mitotane treatment. OBJECTIVE: Our objective was to define the impact of mitotane
      treatment on in vivo steroidogenesis in patients with ACC. SETTING AND DESIGN: At
      seven European specialist referral centers for adrenal tumors, we analyzed 24-h
      urine samples (n = 127) collected from patients with ACC before and during
      mitotane therapy in the adjuvant setting (n = 23) or for metastatic ACC (n =
      104). Urinary steroid metabolite excretion was profiled by gas
      chromatography/mass spectrometry in comparison with healthy controls (n = 88).
      RESULTS: We found a sharp increase in the excretion of 6beta-hydroxycortisol over
      cortisol (P < 0.001), indicative of a strong induction of the major drug
      metabolizing enzyme cytochrome P450 3A4. The contribution of 6beta
      hydroxycortisol to total glucocorticoid metabolites increased from 2% (median,
      interquartile range 1-4%) to 56% (39-71%) during mitotane treatment. Furthermore,
      we documented strong inhibition of systemic 5alpha-reductase activity, indicated
      by a significant decrease in 5alpha-reduced steroids, including 5alpha
      tetrahydrocortisol, 5alpha-tetrahydrocorticosterone, and androsterone (all P <
      0.001). The degree of inhibition was similar to that in patients with
      inactivating 5alpha-reductase type 2 mutations (n = 23) and patients receiving
      finasteride (n = 5), but cluster analysis of steroid data revealed a pattern of
      inhibition distinct from these two groups. Longitudinal data showed rapid onset
      and long-lasting duration of the observed effects. CONCLUSIONS: Cytochrome P450
      3A4 induction by mitotane results in rapid inactivation of more than 50% of
      administered hydrocortisone, explaining the need for doubling hydrocortisone
      replacement in mitotane-treated patients. Strong inhibition of 5alpha-reductase
      activity is in line with the clinical observation of relative inefficiency of
      testosterone replacement in mitotane-treated men, calling for replacement by
      5alpha-reduced androgens.

PMID- 23162092
TI  - Results of a single-center observational 10-year survey study on recurrence of
      hyperprolactinemia after pregnancy and lactation.
AB  - CONTEXT: The current survey study investigated the recurrence rate of
      hyperprolactinemia after cabergoline (CAB)-induced pregnancy and after lactation
      as well as safety of CAB exposure during early gestation. PATIENTS AND METHODS:
      From 1997-2008, 143 pregnancies were recorded in 91 patients with
      hyperprolactinemia (age 30.4 +/- 4.7 yr, 76 microadenomas, 10 macroadenomas, and
      five nontumoral hyperprolactinemia). CAB therapy was discontinued within wk 6 of
      gestation in all. Pregnancies were monitored until delivery or termination,
      during and after lactation, twice yearly up to 60 months. The incidence of
      abortions, premature delivery, and fetal malformations was also analyzed.
      RESULTS: Pregnancies resulted in 13 (9.1%) spontaneous abortions and 126 (88.1%)
      live births. No neonatal malformations and/or abnormalities were recorded. In 29
      of 91 patients (three with macroadenomas), treatment with CAB had to be restarted
      within 6 months after lactation because of hyperprolactinemia recurrence, whereas
      in 68% of cases, no additional therapy was required up to 60 months. No tumor
      mass enlargement was observed. All patients but three were breastfeeding, 35
      (38.5%) for less than 2 months and 56 (61.5%) for 2-6 months. Three months after
      cessation of lactation and 60 months after pregnancy, no difference in prolactin
      levels was found between patients nursing for less than 2 months and 2-6 months.
      CONCLUSIONS: Fetal exposure to CAB at conception does not induce any increased
      risk of miscarriage or malformations. Pregnancy is associated with normalization
      of prolactin levels in 68% of patients. Breastfeeding does not increase the
      recurrence rate of hyperprolactinemia.

PMID- 23162093
TI  - Inverse relationship between serum osteocalcin levels and visceral fat area in
      Chinese men.
AB  - OBJECTIVE: The relationship between serum osteocalcin levels and body fat
      distribution remains unclear. This study aimed to investigate the association
      between serum osteocalcin levels and visceral fat area (VFA) in Chinese men.
      DESIGN: Total serum osteocalcin levels were measured in 1768 Chinese men (22-75
      yr old) by electrochemiluminescence immunoassay. VFA was quantified via magnetic
      resonance imaging. Correlation analyses were carried out for serum osteocalcin
      levels and clinical parameters. Subgroup analysis was carried out to confirm the
      correlations using subjects with normal glucose tolerance and normal body mass
      index chosen from the entire study population. RESULTS: Increased serum
      osteocalcin levels were accompanied by a decreasing trend in all anthropometric
      indices of obesity, systolic blood pressure, blood glucose, insulin resistance
      index, triglycerides, free fatty acid, and C-reactive protein levels (all P <
      0.05). The 50-75th (osteocalcin level: 16.18-19.88 ng/ml) and 75th (>=19.89
      ng/ml) percentile groups had lower VFA than the 25th (<=13.11 ng/ml) and 25-50th
      (13.12-16.17 ng/ml) percentile groups (96.0 +/- 44.4 and 89.8 +/- 44.4 cm(2) vs.
      108.1 +/- 41.9 and 102.9 +/- 44.9 cm(2), P < 0.05). A decreasing trend in serum
      osteocalcin levels was found to accompany the increase in VFA. Multiple stepwise
      regression analysis showed that VFA, as an independent factor, was inversely
      associated with serum osteocalcin levels both in the entire study population and
      subgroup population (all P < 0.01). CONCLUSIONS: Serum osteocalcin levels were
      inversely correlated with VFA in Chinese men.

PMID- 23162095
TI  - An unusual giant cell tumor of the thyroid: case report and review of the
      literature.
AB  - CONTEXT: Bone giant cell tumors (GCTs) are among the most common benign bone
      tumors and affect mostly young patients. They represent a rare etiology of head
      and neck cancer. OBJECTIVE: We report the case of a 38-yr-old male with a GCT of
      the thyroid cartilage, initially treated as a thyroid cancer. CASE ILLUSTRATION:
      The patient had incomplete initial surgery, and a substantial tumor residue was
      observed at postoperative morphological evaluation. Given the potential risks
      associated with complete definitive surgery and recent data supporting the use of
      the receptor activator of nuclear factor kappaB ligand inhibitor, we proposed
      treatment with denosumab. Three months after initiating denosumab, computed
      tomography scan imaging showed a significant modification of the lesion with
      several calcifications. The patient underwent partial laryngectomy, and
      examination of the surgical specimen revealed a complete histological response.
      RESULTS: A review of the literature was conducted to identify previous studies
      pertaining to GCTs, focusing on reports related to their management. CONCLUSION:
      Denosumab emerges as a new treatment for patients with GCTs. Additional clinical
      trial data are needed to establish the real efficacy and long-term safety of this
      treatment for the management of GCT.

PMID- 23162094
TI  - Maternal serum 25-hydroxyvitamin D and measures of newborn and placental weight
      in a U.S. multicenter cohort study.
AB  - CONTEXT: Inconsistent associations between maternal vitamin D status and fetal
      size have been published in small studies. OBJECTIVE: Our objective was to
      examine the association between maternal 25-hydroxyvitamin D [25(OH)D] levels and
      measures of newborn and placental weight. DESIGN AND SETTING: We measured
      maternal 25(OH)D in mothers from the Collaborative Perinatal Project, an
      observational cohort conducted in 12 U.S. medical centers from 1959 to 1965.
      PARTICIPANTS: Women delivering singleton, term, live births with 25(OH)D measured
      at a gestation of 26 wk or less (n = 2146). MAIN OUTCOME MEASURES: Birth weight,
      ponderal index, placental weight, the placental to fetal weight ratio, and small
      for gestational age were measured. Hypotheses were formulated after data
      collection. RESULTS: After confounder adjustment, mothers with 25(OH)D of 37.5
      nmol/liter or greater gave birth to newborns with 46 g [95% confidence interval
      (CI), 9-82 g] higher birth weights and 0.13 cm (0.01-0.25 cm) larger head
      circumferences compared with mothers with less than 37.5 nmol/liter. Birth weight
      and head circumference rose with increasing 25(OH)D up to 37.5 nmol/liter and
      then leveled off (P < 0.05). No association was observed between 25(OH)D and
      ponderal index, placental weight, or the placental to fetal weight ratio.
      Maternal 25(OH)D of 37.5 nmol/liter or greater vs. less than 37.5 nmol/liter in
      the first trimester was associated with half the risk of small for gestational
      age (adjusted odds ratio 0.5; 95% CI 0.3-0.9), but no second-trimester
      association was observed. CONCLUSIONS: Maternal vitamin D status is independently
      associated with markers of physiological and pathological growth in term infants.
      Adequately powered randomized controlled trials are needed to test whether
      maternal vitamin D supplementation may improve fetal growth.

PMID- 23162096
TI  - Growth hormone receptor (GHR) exon 3 polymorphism status detection by dual-enzyme
      linked immunosorbent assay (ELISA).
AB  - CONTEXT: GH receptor (GHR) exon 3-deleted/full-length (d3/fl) polymorphism has
      been proposed to affect the responsiveness to GH therapy. Conventional multiplex
      PCR genotyping method for this polymorphism detection requires DNA samples, which
      may be difficult to obtain due to ethical and procedural issues and may limit
      further studies into the role of this polymorphism in health and disease.
      OBJECTIVE: The objective of the study was to develop a simple genotyping
      alternative method for GHRd3 identification by directly measuring serum levels of
      total GH binding protein (tGHBP) and exon 3-positive GHBP[(E3(+)GHBP] by
      immunoassay and thereby assess the GHRd3 status. DESIGN: The GHRd3 genotype was
      determined by PCR, and tGHBP and E3(+)GHBP levels were measured in serum of 88
      healthy adults. MAIN OUTCOME MEASURES: The GHRd3 chemotype by ELISA was compared
      with the genotype by conventional PCR. RESULTS: The concordance rate of GHR exon
      3 status identification between PCR genotyping and ELISA chemotyping was shown to
      be 100%. There were negligible detectable serum levels of E3(+)GHBP in d3/d3
      subjects. The ratio of serum levels E3(+)GHBP vs. tGHBP in fl/fl and d3/fl
      subjects was (mean +/- SD) 96.6 +/- 5.1 and 57.1 +/- 8.4%, respectively (P <
      0.0001). Interestingly, we observed that d3/d3 subjects had significantly lower
      serum levels of tGHBP compared with fl/fl and d3/fl genotypes. CONCLUSIONS: This
      dual ELISA against tGHBP and E3(+)GHBP can be used as an alternative method for
      determining GHRd3 polymorphism status. The implications of differences in serum
      levels of tGHBP among different genotypes and responsiveness to GH therapy need
      to be further investigated.

PMID- 23162097
TI  - Total and high-molecular-weight adiponectin and risk of coronary heart disease
      and ischemic stroke in older adults.
AB  - CONTEXT: Adiponectin is atheroprotective in the laboratory, but prospective
      studies have shown opposite associations with cardiovascular disease (CVD) in
      healthy middle-aged populations (protective) and older cohorts (adverse). Whether
      this relates to different proportions of high-molecular-weight (HMW) adiponectin
      is unknown. OBJECTIVE: The aim of the study was to test the hypothesis that total
      adiponectin is directly associated, but HMW adiponectin is inversely related,
      with CVD in older adults. DESIGN, SETTING, AND PARTICIPANTS: We evaluated 3290
      participants free of prevalent CVD in a longitudinal cohort study of U.S. adults
      aged 65 yr and older. MAIN OUTCOME MEASURES: We measured incident CVD (n = 1291),
      comprising coronary heart disease and ischemic stroke. RESULTS: Total and HMW
      adiponectin were tightly correlated (r = 0.94). Cubic splines adjusted for
      potential confounders revealed that the associations of total and HMW adiponectin
      with CVD were U-shaped, with inflection points of 20 and 10 mg/liter,
      respectively. After controlling for potential confounding, levels of total and
      HMW adiponectin below these cutpoints tended to be inversely associated with
      incident CVD, driven by their significant or near-significant relations with
      coronary heart disease [hazard ratio (HR), 0.85 per sd increase; 95% confidence
      interval (CI), 0.75-96; and HR, 0.87; 95% CI, 0.75-1.01, respectively]. These
      associations were abrogated by additional inclusion of putative metabolic
      intermediates. Above these cutpoints, however, both total and HMW adiponectin
      were significantly directly associated with CVD after adjustment for confounders
      and, particularly, mediators (HR, 1.20 per sd increase; 95% CI, 1.06-1.35; and
      HR, 1.12; 95% CI, 1.02-1.24, respectively). CONCLUSION: In community-living
      elders, total and HMW adiponectin showed similar U-shaped relationships with CVD.
      The inverse relation in the lower range, but not the direct association at the
      higher end, disappeared after inclusion of putative intermediates, suggesting
      that high levels may reflect adverse processes separate from adiponectin's
      beneficial glycometabolic properties.

PMID- 23162098
TI  - Maternal plasma polyunsaturated fatty acid status in late pregnancy is associated
      with offspring body composition in childhood.
AB  - CONTEXT: Maternal diet during pregnancy has been linked to offspring adiposity,
      but it is unclear whether maternal polyunsaturated fatty acid (PUFA) status
      during pregnancy affects offspring body composition. OBJECTIVE: We investigated
      the associations between maternal plasma n-3 and n-6 PUFA status at 34 wk
      gestation and offspring body composition. DESIGN AND SETTING: A prospective
      United Kingdom population-based mother-offspring cohort, the Southampton Women's
      Survey (SWS), was studied. PARTICIPANTS: A total of 12,583 nonpregnant women were
      recruited into the SWS, among whom 1987 delivered a baby before December 31,
      2003; 293 mother-child pairs had complete measurements of maternal plasma PUFA
      concentrations in late pregnancy and offspring body composition at both ages 4
      and 6 yr. MAIN OUTCOMES MEASURED: We measured offspring body composition by dual
      energy x-ray absorptiometry, yielding fat mass, lean mass, percentage fat mass,
      and percentage lean mass. Results are presented as beta-coefficients for
      standardized variables, therefore reflecting the sd change of the outcome for
      every 1 sd of the predictor. RESULTS: After adjustment for maternal factors and
      child factors including height and duration of breast-feeding, maternal plasma n
      6 PUFA concentration positively predicted offspring fat mass at 4 yr (beta = 0.14
      SD/SD; P = 0.01) and 6 yr (beta = 0.11 SD/SD; P = 0.04), but there was no
      association with offspring lean mass at either age (beta = 0.005 SD/SD, P = 0.89;
      and beta = 0.008 SD/SD, P = 0.81, respectively). Maternal plasma n-3 PUFA
      concentration was not associated with offspring fat mass at 4 yr (beta = 0.057
      SD/SD; P = 0.34) or 6 yr (beta = 0.069 SD/SD; P = 0.21). Maternal plasma n-3 PUFA
      status was positively associated with offspring lean mass on univariate analysis
      (4 yr, beta = 0.11, P = 0.06; 6 yr, beta = 0.14; P = 0.02); however, this was
      confounded by a positive association with offspring height. CONCLUSIONS: This
      observational study suggests that maternal n-6 PUFA status during pregnancy might
      influence offspring adiposity in childhood.

PMID- 23162099
TI  - Persistent subclinical hypothyroidism and cardiovascular risk in the elderly: the
      cardiovascular health study.
AB  - CONTEXT: Use of a single set of thyroid function tests to define subclinical
      hypothyroidism may lead to misclassification over time and could influence
      findings from longitudinal studies. OBJECTIVE: We assessed the risks of coronary
      heart disease (CHD), heart failure (HF), and cardiovascular (CV) death in older
      adults with persistent subclinical hypothyroidism. DESIGN, SETTING, AND
      PARTICIPANTS: The study included 679 subclinically hypothyroid and 4184 euthyroid
      U.S. individuals at least 65 yr old enrolled in the Cardiovascular Health Study
      and not taking thyroid preparations. MAIN OUTCOME MEASURE: We measured the 10-yr
      risk of incident CHD, HF, and CV death from persistent subclinical
      hypothyroidism, overall and stratified by degree of TSH elevation (4.5-6.9, 7.0
      9.9, and 10.0-19.9 mU/liter). RESULTS: There was no association between
      persistent subclinical hypothyroidism and incident CHD [hazard ratio (HR), 1.12;
      95% confidence interval (CI), 0.93-1.36], HF (HR, 1.05; 95% CI, 0.97-1.27), or CV
      death (HR, 1.07; 95% CI, 0.87-1.31) in adjusted analyses in which subclinical
      hypothyroidism was modeled as a time-varying exposure using up to four serial
      thyroid function tests. When subclinical hypothyroidism was stratified by degree
      of TSH elevation, no significant associations were found in any stratum. Findings
      were similar in fixed exposure analyses in which only participants with testing 2
      yr apart were considered, with no association between persistent or transient
      subclinical hypothyroidism and incident CHD, HF, or CV death. CONCLUSIONS: Our
      data do not support increased risk of CHD, HF, or CV death in older adults with
      persistent subclinical hypothyroidism.

PMID- 23162101
TI  - The metabolic profile in active acromegaly is gender-specific.
AB  - CONTEXT: The sexual dimorphism of the somatotroph axis has been documented, but
      whether the acromegaly-related metabolic alterations are gender-dependent has
      never been investigated. OBJECTIVE: The aim of the study was to evaluate the
      impact of gender on the metabolic parameters in acromegaly. DESIGN: We conducted
      a retrospective, comparative, multicenter study. PATIENTS: The 307 newly
      diagnosed acromegalic patients included in the study were grouped by gender: 157
      men (aged 48.01 +/- 14.28 yr), and 150 women (aged 48.67 +/- 14.95 yr; of which
      77 were premenopausal and 73 postmenopausal). OUTCOME MEASUREMENTS: We measured
      each component of the metabolic syndrome (MS), hemoglobin A1c, the areas under
      the curve (AUCs) of glucose and insulin during 2-h oral glucose tolerance test,
      basal insulin resistance using the homeostasis model assessment of the insulin
      resistance index, stimulated insulin sensitivity using the insulin sensitivity
      index, early insulin-secretion rate using the insulinogenic index, beta-cell
      function relative to insulin sensitivity using the oral disposition index and the
      visceral adiposity index (VAI) as the surrogate of visceral fat function.
      RESULTS: Women showed a higher prevalence of MS (P < 0.001), higher fasting
      insulin levels (P < 0.001), AUC for insulin (P = 0.002), homeostasis model
      assessment of the insulin resistance index (P < 0.001), and VAI (P < 0.001) and a
      lower insulin sensitivity index (P = 0.002) than men, whereas no difference was
      found in fasting glucose, AUC for glucose, hemoglobin A1c, insulinogenic index,
      and oral disposition index. In women, fasting glucose and fasting insulin showed
      a significant trend toward increase (P < 0.001) and decrease (P = 0.004),
      respectively, from the first to the fourth quartiles of age, whereas VAI showed a
      trend toward increase in both groups (P < 0.001). A significantly higher
      prevalence of MS (P < 0.001), increased waist circumference (P < 0.001), low high
      density lipoprotein cholesterol (P < 0.001), and overt diabetes mellitus (P <
      0.001) was found in postmenopausal women compared with premenopausal women, as
      well as with men. CONCLUSIONS: The majority of metabolic features in acromegaly
      are gender-specific. Active acromegaly in women is strongly associated with
      higher visceral adiposity dysfunction, insulin resistance, and the features of
      MS. We suggest more accurate metabolic management in acromegalic women,
      especially in the postmenopausal years.

PMID- 23162100
TI  - Effect of potassium citrate on bone density, microarchitecture, and fracture risk
      in healthy older adults without osteoporosis: a randomized controlled trial.
AB  - CONTEXT: The acid load imposed by a modern diet may play an important role in the
      pathophysiology of osteoporosis. OBJECTIVE: Our objective was to evaluate the
      skeletal efficacy and safety and the effect on fracture prediction of K-citrate
      to neutralize diet-induced acid loads. DESIGN AND SETTING: We conducted a
      randomized, double-blind, placebo-controlled trial at a teaching hospital.
      SUBJECTS: Subjects included 201 elderly (>65 yr old) healthy men and women (t
      score of -0.6 at lumbar spine). INTERVENTION: Intervention was 60 mEq of K
      citrate daily or placebo by mouth. All subjects received calcium and vitamin D.
      OUTCOME MEASURES: The primary outcome was change in areal bone mineral density
      (aBMD) at the lumbar spine by dual-energy x-ray absorptiometry after 24 months.
      Secondary endpoints included changes in volumetric density and microarchitectural
      parameters by high-resolution peripheral quantitative computed tomography in both
      radii and both tibiae and fracture risk assessment by FRAX (Switzerland).
      RESULTS: K-citrate increased aBMD at lumbar spine from baseline by 1.7 +/- 1.5%
      [95% confidence interval (CI) = 1.0-2.3, P < 0.001] net of placebo after 24
      months. High-resolution peripheral quantitative computed tomography-measured
      trabecular densities increased at nondominant tibia (1.3 +/- 1.3%, CI = 0.7-1.9,
      P < 0.001) and nondominant radius (2.0 +/- 2.0%, CI = 1.4-2.7, P < 0.001). At
      nondominant radius, trabecular bone volume/tissue volume increased by 0.9 +/-
      0.8%, (CI = 0.1-1.7), trabecular thickness by 1.5 +/- 1.6% (CI = 0.7-2.3), and
      trabecular number by 1.9 +/- 1.8% (CI = 0.7-3.1, for all, P < 0.05). K-citrate
      diminished fracture prediction score by FRAX significantly in both sexes.
      CONCLUSIONS: Among a group of healthy elderly persons without osteoporosis,
      treatment with K-citrate for 24 months resulted in a significant increase in aBMD
      and volumetric BMD at several sites tested, while also improving bone
      microarchitecture. Based on the effect on fracture prediction, an effect on
      future fractures by K-citrate is possible.

PMID- 23162102
TI  - Blood erythrocyte and hemoglobin concentrations in premature adrenarche.
AB  - CONTEXT: Premature adrenarche (PA) is characterized by an earlier than normal
      increase in adrenocortical androgen production, and it is associated with
      increased serum IGF-I concentrations. Both the GH-IGF system and androgens,
      particularly testosterone, are known to enhance erythropoiesis. OBJECTIVE: Our
      objective was to test the hypothesis that blood erythrocyte count and blood
      hemoglobin (B-Hb) concentration are increased in PA. DESIGN, PARTICIPANTS, AND
      SETTING: Sixty-four prepubertal children (10 boys) with clinically and
      biochemically defined PA and 62 healthy prepubertal controls (10 boys)
      participating in our Premature Adrenarche study were examined, and a fasting
      blood sample was drawn at a university hospital. MAIN OUTCOME MEASURES: We
      evaluated B-Hb and erythrocyte, thrombocyte, and leukocyte counts and their
      association with serum dehydroepiandrosterone sulfate (DHEAS), testosterone and
      IGF-I concentrations. RESULTS: Children with PA had higher mean blood erythrocyte
      count (4.74 vs. 4.64 * 10(12)/liter, P = 0.04; significant difference in girls
      but not in boys) and a tendency toward higher B-Hb (130 vs. 128 g/liter, P =
      0.06) than their controls. No difference was observed in leukocyte or thrombocyte
      counts between the study groups. In linear regression models including age, sex,
      body mass index SD score, IGF-I, and DHEAS or testosterone, B-Hb was associated
      with serum DHEAS (P = 0.04), testosterone (P = 0.01), and IGF-I (P <= 0.003)
      concentrations in the entire study cohort and with IGF-I separately in girls (P
      <= 0.02). Similar models showed a significant association of blood erythrocyte
      count with serum IGF-I concentration (P = 0.003-0.049) but not with DHEAS or
      testosterone. CONCLUSIONS: Increased erythrocyte count in PA girls suggests that
      relatively small increases in serum androgen or IGF-I concentrations during
      adrenarche may associate with enhanced erythropoiesis.

PMID- 23162103
TI  - Therapy of hypoparathyroidism with PTH(1-84): a prospective four-year
      investigation of efficacy and safety.
AB  - CONTEXT: PTH may be an effective treatment option for hypoparathyroidism, but
      long-term data are not available. OBJECTIVE: We studied the effect of 4 yr of
      PTH(1-84) treatment in hypoparathyroidism. DESIGN: Twenty-seven subjects were
      treated with PTH(1-84) for 4 yr, with prospective monitoring of calcium and
      vitamin D requirements, serum and urinary calcium, serum phosphorus, bone
      turnover markers, and bone mineral density (BMD). RESULTS: Treatment with PTH(1
      84) reduced supplemental calcium requirements by 37% (P = 0.006) and 1,25
      dihydroxyvitamin D requirements by 45% (P = 0.008). Seven subjects (26%) were
      able to stop 1,25-dihydroxyvitamin D completely. Serum calcium concentration
      remained stable, and urinary calcium and phosphorus excretion fell. Lumbar spine
      BMD increased by 5.5 +/- 9% at 4 yr (P < 0.0001). Femoral neck and total hip BMD
      remained stable. At 4 yr, distal radius BMD was not different from baseline. Bone
      turnover markers increased significantly, reaching a 3-fold peak from baseline
      values at 6-12 months (P < 0.05 for all), subsequently declining to steady-state
      levels at 30 months. Hypercalcemia was uncommon (11 episodes in eight subjects
      over 4 yr; 1.9% of all values), with most episodes occurring within the first 6
      months and resolving with adjustment of supplemental calcium and vitamin D.
      CONCLUSIONS: PTH(1-84) treatment of hypoparathyroidism for up to 4 yr maintains
      the serum calcium concentration, while significantly reducing supplemental
      calcium and 1,25-dihydroxyvitamin D requirements. Lumbar spine BMD increases
      without significant changes at other sites. These data provide support for the
      safety and efficacy of PTH(1-84) therapy in hypoparathyroidism for up to 4 yr.

PMID- 23162104
TI  - Metabolic profile in growth hormone-deficient (GHD) adults after long-term
      recombinant human growth hormone (rhGH) therapy.
AB  - BACKGROUND: The metabolic effects of recombinant human GH (rhGH) therapy in
      adults are well-documented in the short term. The effects of long-term rhGH
      therapy beyond 5 yr on metabolic parameters are presently unknown. OBJECTIVE: The
      aim of the study was to evaluate the long-term effects of rhGH treatment on
      biochemical and anthropometric parameters in a large cohort of GH-deficient
      adults. METHODS: Ninety-eight GH-deficient adult patients treated with rhGH for
      at least 10 yr were included (mean age, 59.4 yr; 50% female). Total cholesterol,
      high-density lipoprotein cholesterol, low-density lipoprotein cholesterol,
      triglycerides, anthropometric parameters, IGF-I, and glucose were evaluated at
      baseline and after 5, 10, and 15 yr of treatment. In addition, the prevalence of
      the metabolic syndrome (MS) and the incidence of cardiovascular events were
      assessed. RESULTS: Total cholesterol and low-density lipoprotein cholesterol
      concentrations were lower, and high-density lipoprotein cholesterol levels were
      significantly higher during long-term rhGH replacement when compared to baseline
      (all P < 0.001). Both waist circumference (P < 0.001) and body mass index (P =
      0.018) were significantly higher after 10 yr, as were fasting plasma glucose
      levels (P < 0.001). No significant changes were observed in triglycerides, waist
      to-hip ratio, and blood pressure during follow-up. In the subset of patients with
      15-yr rhGH treatment (n = 43), generally similar metabolic effects were found. MS
      prevalence was increased after 10 yr of rhGH treatment (57.1 vs. 32.7%; P <
      0.001), especially in males (69.4 vs. 32.7%; P < 0.001). CONCLUSION: Despite
      improvement of several cardiovascular risk factors, MS prevalence increased
      significantly during rhGH treatment. The effect of long-term rhGH treatment on
      overall cardiovascular risk profile needs to be established in a larger cohort.

PMID- 23162105
TI  - Imaging work-up for screening of paraganglioma and pheochromocytoma in SDHx
      mutation carriers: a multicenter prospective study from the PGL.EVA
      Investigators.
AB  - CONTEXT: Recommendations have not been established concerning imaging to screen
      SDHx mutation carriers for paraganglioma and pheochromocytoma. OBJECTIVE: Our
      objective was to compare the performance of gadolinium-enhanced magnetic
      resonance angiography, contrast-enhanced computed tomography, and
      [(123)I]metaiodo-benzylguanidine and somatostatin receptor scintigraphies for
      detecting head and neck and thoracic-abdominal-pelvic paragangliomas in SDHx
      mutation carriers. DESIGN AND SETTING: We conducted a prospective, multicenter
      study from June 2005 to December 2009 at 23 French medical centers. PATIENTS: A
      total of 238 index cases or relatives carrying mutations in SDHD, SDHB, or SDHC
      genes were included. INTERVENTION: Images obtained by each technique were
      analyzed blind, without knowledge of results from other tests, first in each
      local center and then centrally. MAIN OUTCOME MEASURES: We evaluated sensitivity,
      specificity, and likelihood ratios for individual and combinations of tests, the
      gold standard being the consensus of an expert committee. RESULTS: Two hundred
      two tumors were diagnosed in 96 subjects. At local assessment, the sensitivity of
      anatomical imaging for detecting all tumors was higher (85.7%) than that of both
      scintigraphic techniques (42.7% for [(123)I]metaiodo-benzylguanidine and 69.5%
      for somatostatin receptor scintigraphy), except for thoracic localizations where
      somatostatin receptor scintigraphy was more sensitive (61.5 vs. 46.2% for
      anatomical imaging and 30.8% for [(123)I]metaiodo-benzylguanidine scintigraphy).
      The best diagnostic performance during local assessment was obtained by combining
      anatomical imaging tests and somatostatin receptor scintigraphy (sensitivity
      91.7%). Central assessment significantly increased the sensitivity (98.6%) of
      tests in combination. CONCLUSIONS: In routine practice, the imaging work-up for
      screening SDHx mutation carriers should include thoraco-abdomino-pelvic computed
      tomography, head and neck magnetic angiography, and somatostatin receptor
      scintigraphy. Expert centralized image assessment is recommended.

PMID- 23162106
TI  - Endothelial progenitor cells in mothers of low-birthweight infants: a link
      between defective placental vascularization and increased cardiovascular risk?
AB  - CONTEXT: Offspring birthweight is inversely associated with future maternal
      cardiovascular mortality, a relationship that has yet to be fully elucidated.
      Endothelial progenitor cells (EPCs) are thought to play a key role in
      vasculogenesis, and EPC numbers reflect cardiovascular risk. OBJECTIVE: Our
      objective was to ascertain whether EPC number or function was reduced in mothers
      of low-birthweight infants. DESIGN AND SETTING: This was a prospective cohort
      study in a general antenatal department of a university maternity hospital.
      PARTICIPANTS: Twenty-three mothers of small for gestational age (SGA) infants
      (birthweight < 10th centile) and 23 mothers of appropriate for gestational age
      (AGA) infants (birthweight >= 10th centile) were recruited. MAIN OUTCOME
      MEASURES: Maternal EPC number and function, conventional cardiovascular risk
      markers, and cord blood adiponectin were measured. RESULTS: Median EPC count was
      lower (294 vs. 367, P = 0.005) and EPC migration was reduced (0.91 vs. 1.59, P <
      0.001) in SGA compared with AGA infants, with no difference in EPC adhesion
      (0.221 vs. 0.284 fluorescence units, P = 0.257). Maternal triglyceride levels
      were higher in SGA than AGA infants (0.98 vs. 0.78 mmol/liter, P = 0.006), but
      there was no difference in cholesterol, glucose, insulin, glycosylated
      hemoglobin, adiponectin, or blood pressure. There was a moderate monotone
      (increasing) relationship between birthweight and umbilical cord blood
      adiponectin (r = 0.475, P = 0.005). CONCLUSION: Giving birth to an SGA infant was
      associated with lower maternal EPC number and reduced migratory function. Cord
      blood adiponectin was significantly correlated with birthweight.

PMID- 23162107
TI  - Over-expression of phosphorylated mammalian target of rapamycin is associated
      with poor survival in oesophageal adenocarcinoma: a tissue microarray study.
AB  - BACKGROUND: Protein kinase mammalian target of rapamycin (mTOR) is an important
      downstream effector of the phosphatidylinositol 3-kinase (PI3K)/Akt signalling
      pathway. In several tumour types, phosphorylated mTOR (p-mTOR) over-expression is
      an independent prognostic marker for poor survival. However, p-mTOR expression
      has not been assessed in oesophageal adenocarcinoma (OAC). MATERIALS AND METHODS:
      Tumour cores of 154 patients with OAC were included in a tissue microarray (TMA).
      Scoring criteria were based on p-mTOR staining intensity. RESULTS: 147 (95.5%)
      patients were available for immunohistochemical evaluation. Over-expression of p
      mTOR was detected in 29 (19.7%) tumours, whereas 118 (80.3%) patients showed
      negative expression. Over-expression was significantly associated with poor
      overall survival in univariate analysis (HR 1.648; 95% CI 1.019 to 2.664;
      p=0.042). Median survival was 21.2 months in patients with p-mTOR over-expression
      and 29.0 in the negative p-mTOR group (p=0.040). In addition, a trend towards p
      mTOR over-expression and vasoinvasive growth was seen (p=0.057). In multivariate
      analysis, including clinical and pathological variables (p<0.10), only T-stage
      (HR 2.795; 95% CI 1.343 to 5.813; p=0.006) and differentiation grade (HR 2.198;
      95% CI 1.353 to 3.570; p=0.001) were independent prognostic markers of poor
      survival. CONCLUSION: p-mTOR over-expression was detected in 19.7% of patients
      with OAC and was associated with poor overall survival.

PMID- 23162108
TI  - Anatomical basis and histopathological changes resulting from selective internal
      radiotherapy for liver metastases.
AB  - BACKGROUND: Knowledge that liver tumours preferentially take their blood supply
      from the arterial blood supply rather than the portal venous system can be used
      for local delivery of treatment or for embolisation to cut off the blood supply
      to tumours. AIMS: To present histological evaluation of malignant and non
      malignant hepatic tissue of one such therapy, selective internal radiation
      therapy (SIRT) with yttrium-90 microspheres, to decipher its principal mechanism
      of action. METHODS: The H&E stained sections of hepatic resection specimens from
      three patients with liver metastases from colorectal (CRC) cancer, who underwent
      hepatic surgery 4-9 months following SIRT, were examined and the pathological
      changes documented. RESULTS: Resin microspheres were identified in the vascular
      tumour bed and vessels within the portal tracts of the background liver
      parenchyma. Microspheres were usually associated with giant cell reaction or
      histiocytes. In the tumour bed, tumour necrosis, mucinous alteration, collections
      of foamy histiocytes, ectatic vessels, calcification and fibrosis were observed.
      There was minimal cellular inflammatory response observed, suggestive of direct
      radiation injury as a non-immune mediated process. CONCLUSIONS: We describe in
      detail the spectrum of histopathological changes in malignant tissue and liver
      parenchyma in patients with metastatic CRC treated with SIRT. Our findings are
      consistent with the hypothesis that the principal mechanism of action of SIRT
      appears to be via arterially directed delivery of highly radioactive microspheres
      in and around the vascular tumour bed rather than by micro-arterial embolisation.

PMID- 23162109
TI  - Participation of natural killer cells in the pathogenesis of bile duct lesions in
      biliary atresia.
AB  - AIMS: Immunological disturbances including innate immunity after a suspected
      viral infection are considered important to the pathogenesis of bile duct lesions
      in cases of biliary atresia (BA). In this study, we tried to evaluate whether
      natural killer (NK) cells and CX3CL1 (Fractalkine) and its receptor (CX3CR1) are
      involved in the bile duct injury. METHODS: Using the section of BA (22 cases) and
      controls, immunohistochemistry for CD56, CD16, CD68, CX3CL1 and CX3CR1 was
      performed. Moreover, using cultured biliary epithelial cells (BECs) and NK cells,
      the production of CX3CL1 in BECs and the migration of NK cells were evaluated.
      RESULTS: It was found that CD56(-)CD16(+)CD68(-) NK cells were increased around
      the damaged small and large bile ducts in BA and hepatitis C virus-related
      chronic hepatitis in comparison with other controls. CX3CL1 was strongly
      expressed on the damaged bile ducts in BA, while this expression was relatively
      weak or absent in the bile ducts of normal liver. The results suggest the CD56(
      )CD16(+) NK cells to be involved in the development of bile duct injuries in BA.
      These CD16(+) NK cells were positive for CX3CR1, and attracted by CX3CL1
      expressed on bile ducts. Further study revealed that stimulation with poly(I:C)
      (a synthetic analogue of viral dsRNA) increased the expression of CX3CL1 on
      cultured BECs followed by increased migrational activity of cultured NK cells.
      CONCLUSIONS: CD56(-)CD16(+) NK cells with reduced NK activity may be involved in
      the bile duct damage in BA, and CD16(+) NK cells expressing CX3CR1 may be
      attracted by and interact with bile ducts expressing CX3CL1.

PMID- 23162110
TI  - Watery diarrhea in an immune-competent traveler.

PMID- 23162111
TI  - Need for rigor in design, reporting, and interpretation of transcriptomic
      biomarker studies.

PMID- 23162114
TI  - Xylem tissue specification, patterning, and differentiation mechanisms.
AB  - Vascular plants (Tracheophytes) have adapted to a variety of environments ranging
      from arid deserts to tropical rainforests, and now comprise >250,000 species.
      While they differ widely in appearance and growth habit, all of them share a
      similar specialized tissue system (vascular tissue) for transporting water and
      nutrients throughout the organism. Plant vascular systems connect all plant
      organs from the shoot to the root, and are comprised of two main tissue types,
      xylem and phloem. In this review we examine the current state of knowledge
      concerning the process of vascular tissue formation, and highlight important
      mechanisms underlying key steps in vascular cell type specification, xylem and
      phloem tissue patterning, and, finally, the differentiation and maturation of
      specific xylem cell types.

PMID- 23162115
TI  - An extracellular lipid transfer protein is relocalized intracellularly during
      seed germination.
AB  - Plant lipid transfer proteins (LTPs) constitute a family of small proteins
      recognized as being extracellular. In agreement with this notion, several lines
      of evidence have shown the apoplastic localization of HaAP10, a LTP from
      Helianthus annuus dry seeds. However, HaAP10 was recently detected
      intracellularly in imbibing seeds. To clarify its distribution,
      immunolocalization experiments were performed during the course of germination
      and confirmed its intracellular localization upon early seed imbibition. Further
      assays using a hydrophobic dye, FM4-64, inhibitors of vesicular traffic, and
      immunolocalization of the pectin rhamnogalacturonan-II, allowed the conclusion
      that endocytosis is activated as soon as seed imbibition starts. Furthermore,
      this study demonstrated that HaAP10 is endocytosed throughout imbibition.
      Biochemical and cellular approaches indicate that the intracellular fraction of
      this LTP appears associated with oil bodies and some evidence also suggest its
      presence in glyoxysomes. So, HaAP10 is apoplastic in dry seeds and upon
      imbibition is rapidly internalized and relocalized to organelles involved in
      lipid metabolism. The results suggest that HaAP10 may be acting as a fatty acid
      shuttle between the oil body and the glyoxysome during seed germination. This
      concept is consistent with the initial proposition that LTPs participate in the
      intracellular transfer of lipids which was further denied based on their apparent
      extracellular localization. This report reveals for the first time the
      relocalization of a lipid transfer protein and opens new perspectives on its
      role.

PMID- 23162116
TI  - Genetic engineering to improve plant performance under drought: physiological
      evaluation of achievements, limitations, and possibilities.
AB  - Fully drought-resistant crop plants would be beneficial, but selection breeding
      has not produced them. Genetic modification of species by introduction of very
      many genes is claimed, predominantly, to have given drought resistance. This
      review analyses the physiological responses of genetically modified (GM) plants
      to water deficits, the mechanisms, and the consequences. The GM literature
      neglects physiology and is unspecific in definitions, which are considered here,
      together with methods of assessment and the type of drought resistance resulting.
      Experiments in soil with cessation of watering demonstrate drought resistance in
      GM plants as later stress development than in wild-type (WT) plants. This is
      caused by slower total water loss from the GM plants which have (or may have
      morphology is often poorly defined) smaller total leaf area (LA) and/or decreased
      stomatal conductance (g   (s)), associated with thicker laminae (denser mesophyll
      and smaller cells). Non-linear soil water characteristics result in extreme
      stress symptoms in WT before GM plants. Then, WT and GM plants are rewatered:
      faster and better recovery of GM plants is taken to show their greater drought
      resistance. Mechanisms targeted in genetic modification are then, incorrectly,
      considered responsible for the drought resistance. However, this is not valid as
      the initial conditions in WT and GM plants are not comparable. GM plants exhibit
      a form of 'drought resistance' for which the term 'delayed stress onset' is
      introduced. Claims that specific alterations to metabolism give drought
      resistance [for which the term 'constitutive metabolic dehydration tolerance'
      (CMDT) is suggested] are not critically demonstrated, and experimental tests are
      suggested. Small LA and g   (s) may not decrease productivity in well-watered
      plants under laboratory conditions but may in the field. Optimization of GM
      traits to environment has not been analysed critically and is required in field
      trials, for example of recently released oilseed rape and maize which show
      'drought resistance', probably due to delayed stress onset. Current evidence is
      that GM plants may not be better able to cope with drought than selection-bred
      cultivars.

PMID- 23162117
TI  - Identification and profiling of arsenic stress-induced microRNAs in Brassica
      juncea.
AB  - MicroRNAs (miRNAs) constitute a novel mechanism of gene regulation affecting
      plant development, growth, and stress response. To study the role of miRNAs in
      arsenic (As) stress, microarray profiling of miRNAs was performed in Brassica
      juncea using a custom Phalanx Plant OneArray containing 381 unique miRNA probes
      representing 618 miRNAs from 22 plant species. miRNA microarray hybridization of
      roots exposed to As for 1h and 4h revealed that a total of 69 miRNAs belonging to
      18 plant miRNA families had significantly altered expression. The As-responsive
      miRNAs also exhibited a time- and organ-dependent change in their expression.
      Putative target prediction for the miRNAs suggested that they regulate various
      developmental processes (e.g. miR156, miR169, and miR172), sulphur uptake,
      transport, and assimilation (miR395, miR838, and miR854), and hormonal
      biosynthesis and/or function (e.g. miR319, miR167, miR164, and miR159). Notable
      changes were observed in the level of auxins [indole-3-acetic acid (IAA), indole
      3- butyric acid, and naphthalene acetic acid], jasmonates [jasmonic acid (JA) and
      methyl jasmonate], and abscisic acid. The exogenous supply of JA and IAA improved
      growth of plants under As stress and altered expression of miR167, miR319, and
      miR854, suggesting interplay of hormones and miRNAs in the regulation of As
      response. In conclusion, the present work demonstrates the role of miRNAs and
      associated mechanisms in the plant's response towards As stress.

PMID- 23162118
TI  - Rubisco activity and regulation as targets for crop improvement.
AB  - Rubisco (ribulose-1,5-bisphosphate (RuBP) carboxylase/oxygenase) enables net
      carbon fixation through the carboxylation of RuBP. However, some characteristics
      of Rubisco make it surprisingly inefficient and compromise photosynthetic
      productivity. For example, Rubisco catalyses a wasteful reaction with oxygen that
      leads to the release of previously fixed CO(2) and NH(3) and the consumption of
      energy during photorespiration. Furthermore, Rubisco is slow and large amounts
      are needed to support adequate photosynthetic rates. Consequently, Rubisco has
      been studied intensively as a prime target for manipulations to 'supercharge'
      photosynthesis and improve both productivity and resource use efficiency. The
      catalytic properties of Rubiscos from diverse sources vary considerably,
      suggesting that changes in turnover rate, affinity, or specificity for CO(2) can
      be introduced to improve Rubisco performance in specific crops and environments.
      While attempts to manipulate plant Rubisco by nuclear transformation have had
      limited success, modifying its catalysis by targeted changes to its catalytic
      large subunit via chloroplast transformation have been much more successful.
      However, this technique is still in need of development for most major food crops
      including maize, wheat, and rice. Other bioengineering approaches for improving
      Rubisco performance include improving the activity of its ancillary protein,
      Rubisco activase, in addition to modulating the synthesis and degradation of
      Rubisco's inhibitory sugar phosphate ligands. As the rate-limiting step in carbon
      assimilation, even modest improvements in the overall performance of Rubisco pose
      a viable pathway for obtaining significant gains in plant yield, particularly
      under stressful environmental conditions.

PMID- 23162119
TI  - Exine dehiscing induces rape microspore polarity, which results in different
      daughter cell fate and fixes the apical-basal axis of the embryo.
AB  - The roles of cell polarity and the first asymmetric cell division during early
      embryogenesis in apical-basal cell fate determination remain unclear. Previously,
      a novel Brassica napus microspore embryogenesis system was established, by which
      rape exine-dehisced microspores were induced by physical stress. Unlike
      traditional microspore culture, cell polarity and subsequent asymmetric division
      appeared in the exine-dehisced microspore, which finally developed into a typical
      embryo with a suspensor. Further studies indicated that polarity is critical for
      apical-basal cell fate determination and suspensor formation. However, the
      pattern of the first division was not only determined by cell polarity but was
      also regulated by the position of the ruptured exine. The first division could be
      equal or unequal, with its orientation essentially perpendicular to the polar
      axis. In both types of cell division, the two daughter cells could have different
      cell fates and give rise to an embryo with a suspensor, similar to zygotic apical
      basal cell differentiation. The alignment of the two daughter cells is consistent
      with the orientation of the apical-basal axis of future embryonic development.
      Thus, the results revealed that exine dehiscing induces rape microspore
      polarization, and this polarity results in a different cell fate and fixes the
      apical-basal axis of embryogenesis, but is uncoupled from cell asymmetric
      division. The present study demonstrated the relationships among cell polarity,
      asymmetric cell division, and cell fate determination in early embryogenesis.

PMID- 23162120
TI  - Physiological and genetic analysis of Arabidopsis thaliana anthocyanin
      biosynthesis mutants under chronic adverse environmental conditions.
AB  - Anthocyanin production is a characteristic response of flowering plants to
      unfavourable environmental conditions. The potential roles of flavonoids and
      anthocyanins in plant growth were investigated by growing Arabidopsis thaliana
      anthocyanin production mutants (transparent testa) under limiting nitrogen and
      high light conditions. Inability to produce kaempferol or subsequent intermediate
      compounds by some transparent testa lines was correlated with less biomass
      accumulation in mature plants compared with wild-type control plants under all
      growth conditions tested. However, under both limiting nitrogen and high light
      chronic stress conditions, mutant lines defective in later steps of the
      anthocyanin production pathway produced the same or more biomass than wild-type
      plants. No difference in senescence between transparent testa and wild-type
      plants was found using chlorophyll catabolism and SAG12 expression measurements,
      and no mutants were impaired in the ability to remobilize nutrients from the
      vegetative to reproductive tissues. Moreover, the absence of anthocyanin and/or
      upstream flavonoids does not affect the ability of plants to respond to limiting
      nitrogen by reducing photosynthetic capacity. These results support a role for
      kaempferol and quercetin accumulation in normal plant growth and development.
      Further, the absence of anthocyanins has no effect on plant growth under the
      chronic stress conditions tested.

PMID- 23162121
TI  - Chloroplast transformation for engineering of photosynthesis.
AB  - Many efforts are underway to engineer improvements in photosynthesis to meet the
      challenges of increasing demands for food and fuel in rapidly changing
      environmental conditions. Various transgenes have been introduced into either the
      nuclear or plastid genomes in attempts to increase photosynthetic efficiency. We
      examine the current knowledge of the critical features that affect levels of
      expression of plastid transgenes and protein accumulation in transplastomic
      plants, such as promoters, 5' and 3' untranslated regions, RNA-processing sites,
      translation signals and amino acid sequences that affect protein turnover. We
      review the prior attempts to manipulate the properties of ribulose-1,5
      bisphosphate carboxylase oxygenase (Rubisco) through plastid transformation. We
      illustrate how plastid operons could be created for expression of the multiple
      genes needed to introduce new pathways or enzymes to enhance photosynthetic rates
      or reduce photorespiration. We describe here the past accomplishments and future
      prospects for manipulating plant enzymes and pathways to enhance carbon
      assimilation through plastid transformation.

PMID- 23162122
TI  - The role of L-ascorbic acid recycling in responding to environmental stress and
      in promoting plant growth.
AB  - L-Ascorbic acid (Asc) is the most abundant water-soluble antioxidant in plants.
      It serves as a cofactor for enzymes involved in photosynthesis, hormone
      biosynthesis, and the regeneration of antioxidants such as alpha-tocopherol. Once
      used, Asc can be recycled by several different mechanisms. The short-lived
      monodehydroascorbate (MDHA) radical, produced following Asc oxidation, can be
      recycled following reduction by ferredoxin or monodehydroascorbate reductase
      (MDAR). MDHA can also undergo disproportionation into dehydroascorbate (DHA) and
      Asc. DHA can be recycled into Asc by dehydroascorbate reductase (DHAR) before it
      undergoes irrevocable hydrolysis. Through its recycling, Asc content and its
      redox state are maintained, which is critical under conditions of high demand,
      for example during high light or other stress conditions that increase reactive
      oxygen species (ROS) production. This review provides an overview of research in
      the last decade revealing the role that Asc recycling plays during germination,
      growth, and reproduction, as well as in response to environmental stress. These
      findings highlight the importance of DHAR- and MDAR-mediated mechanisms of Asc
      recycling in maintaining ROS at non-damaging levels while modulating ROS
      signalling function.

PMID- 23162123
TI  - A novel family of gamma-gliadin genes are highly regulated by nitrogen supply in
      developing wheat grain.
AB  - Six wheat cultivars were grown at Rothamsted (UK) with three levels of nitrogen
      fertilizer (100, 200 and 350 kg N/ha) in 2009 and 2010. Gene expression in
      developing caryopses at 21 days post-anthesis (DPA) was profiled using the
      Affymetrix Wheat GeneChip. Four of 105 transcripts which were significantly
      upregulated by nitrogen level were annotated as gamma-3 hordein and the
      identification of corresponding expressed sequence tags showed that they differed
      in sequence from previously described (typical) gamma-gliadins and represented a
      novel form of gamma-gliadin. Real-time reverse transcriptase PCR at 14, 21, 28
      and 35 DPA revealed that this transcript was most abundant and most responsive to
      nitrogen at 21 DPA. Four novel gamma-gliadin genes were isolated by PCR
      amplification from wheat cv. Hereward and the related species Aegilops tauschii
      and Triticum monococcum while three were assembled from the genomic sequence
      database of wheat cv. Chinese Spring (www.cerealsdb.uk.net). Comparison of the
      deduced amino acid sequences of the seven genes showed that they shared only 44.4
      46.0% identity with the sequence of a typical gamma-gliadin (accession number
      EF15018), but 61.8-68.3% identity with the sequence of gamma-3 hordein from the
      wild barley species Hordeum chilense (AY338065). The novel gamma-gliadin genes
      were localized to the group 1 chromosomes (1A, 1B, 1D).

PMID- 23162124
TI  - Floret development and grain setting differences between modern durum wheats
      under contrasting nitrogen availability.
AB  - Wheat yield depends on the number of grains per square metre, which in turn is
      related to the number of fertile  florets at anthesis. The dynamics of floret
      generation/degeneration were studied in contrasting conditions of nitrogen (N)
      and water availability of modern, well-adapted, durum wheats in order to
      understand further the bases for grain number determination. Experiments were
      carried out during the 2008-2009 and 2009-2010 growing seasons at Lleida (NE
      Spain). The first experiment involved four cultivars (Claudio, Donduro, Simeto,
      and Vitron) and two contrasting N availabilities (50 kgN ha(-1) and 250 kgN ha(
      1); N50 and N250) while experiment 2 included the two cultivars most contrasting
      in grain setting responsiveness to N in experiment 1, and two levels of N (N50
      and N250), under irrigated (IR) and rainfed (RF) conditions. In addition, a
      detillering treatment was imposed on both cultivars under the IR+N250 condition.
      The number of fertile florets at anthesis was increased by ~30% in response to N
      fertilization (averaging across treatments and spikelet positions). The effect of
      N and water availability was evident on floret developmental rates from the third
      floret primordium onwards, as these florets in the central spikelets of all
      genotypes reached the stage of a fertile floret in N250 while in N50 they did
      not. In this study, clear differences were found between the cultivars in their
      responsiveness to N by producing more fertile florets at anthesis (through
      accelerating developmental rates of floret primordia), by increasing the
      likelihood of particular grains to be set, or by both traits.

PMID- 23162125
TI  - Environmental and T cell-intrinsic factors limit the expansion of neonatal
      follicular T helper cells but may be circumvented by specific adjuvants.
AB  - Follicular Th (T(FH)) cells have emerged as a new Th subset providing help to B
      cells and supporting their differentiation into long-lived plasma cells or memory
      B cells. Their differentiation had not yet been investigated following neonatal
      immunization, which elicits delayed and limited germinal center (GC) responses.
      We demonstrate that neonatal immunization induces CXCR5(high)PD-1(high) CD4(+)
      T(FH) cells that exhibit T(FH) features (including Batf, Bcl6, c-Maf, ICOS, and
      IL-21 expression) and are able to migrate into the GCs. However, neonatal T(FH)
      cells fail to expand and to acquire a full-blown GC T(FH) phenotype, as reflected
      by a higher ratio of GC T(FH)/non-GC CD4(+) T cells in immunized adults than
      neonates (3.8 * 10(-3) versus 2.2 * 10(-3), p = 0.01). Following the adoptive
      transfer of naive adult OT-II CD4(+) T cells, OT-II T(FH) cells expand in the
      vaccine-draining lymph nodes of immunized adult but not infant recipients,
      whereas naive 2-wk-old CD4(+) OT-II cells failed to expand in adult hosts,
      reflecting the influence of both environmental and T cell-intrinsic factors.
      Postponing immunization to later in life increases the number of T(FH) cells in a
      stepwise manner, in direct correlation with the numbers of GC B cells and plasma
      cells elicited. Remarkably, adjuvantation with CpG oligonucleotides markedly
      increased GC T(FH) and GC B cell neonatal responses, up to adult levels. To our
      knowledge, this is the first demonstration that the T(FH) cell development limits
      early life GC responses and that adjuvants/delivery systems supporting T(FH)
      differentiation may restore adultlike early life GC B cell responses.

PMID- 23162126
TI  - A converse 4-1BB and CD40 ligand expression pattern delineates activated
      regulatory T cells (Treg) and conventional T cells enabling direct isolation of
      alloantigen-reactive natural Foxp3+ Treg.
AB  - Natural regulatory T cells (nTreg) play a central role in the induction and
      maintenance of immunological tolerance. Experimental transplant models and recent
      clinical trials demonstrate that nTreg can control alloreactivity. To upgrade
      Treg-based cell therapies to a selective suppression of undesired immune
      reactions, only the transfer of Ag-specific nTreg represents the appropriate
      therapeutic option. However, Ag-specific nTreg are present at extremely low
      frequencies in the periphery, and so far appropriate surface markers for their
      precise identification are missing. In this study, we demonstrate that activated
      nTreg and activated conventional T cells differ in their 4-1BB and CD40 ligand
      (CD40L) expression signatures, allowing a clear dissection from each other. Based
      on the expression of 4-1BB and absence of CD40L expression, human alloantigen
      reactive Foxp3(+) nTreg can be directly isolated from MLR cultures with high
      purity. Alloantigen-reactive 4-1BB(+)CD40L(-) nTreg were characterized by a
      completely demethylated Treg-specific demethylated region and showed alloantigen
      specific suppressive properties superior to polyclonal Treg. Importantly,
      isolated 4-1BB(+)CD40L(-) nTreg maintain the nTreg phenotype and alloantigen
      reactivity after in vitro expansion. Our results offer the possibility to
      simultaneously analyze Ag-specific nTreg and conventional T cells, and to
      establish cellular therapies with Ag-specific nTreg aiming at a specific
      inhibition of unwanted immunity.

PMID- 23162127
TI  - The capsular polysaccharide Vi from Salmonella typhi is a B1b antigen.
AB  - Vaccination with purified capsular polysaccharide Vi Ag from Salmonella typhi can
      protect against typhoid fever, although the mechanism for its efficacy is not
      clearly established. In this study, we have characterized the B cell response to
      this vaccine in wild-type and T cell-deficient mice. We show that immunization
      with typhoid Vi polysaccharide vaccine rapidly induces proliferation in B1b
      peritoneal cells, but not in B1a cells or marginal zone B cells. This induction
      of B1b proliferation is concomitant with the detection of splenic Vi-specific Ab
      secreting cells and protective Ab in Rag1-deficient B1b cell chimeras generated
      by adoptive transfer-induced specific Ab after Vi immunization. Furthermore, Ab
      derived from peritoneal B cells is sufficient to confer protection against
      Salmonella that express Vi Ag. Expression of Vi by Salmonella during infection
      did not inhibit the development of early Ab responses to non-Vi Ags. Despite
      this, the protection conferred by immunization of mice with porin proteins from
      Salmonella, which induce Ab-mediated protection, was reduced postinfection with
      Vi-expressing Salmonella, although protection was not totally abrogated. This
      work therefore suggests that, in mice, B1b cells contribute to the protection
      induced by Vi Ag, and targeting non-Vi Ags as subunit vaccines may offer an
      attractive strategy to augment current Vi-based vaccine strategies.

PMID- 23162128
TI  - Role of recycling, Mindbomb1 association, and exclusion from lipid rafts of delta
      like 4 for effective Notch signaling to drive T cell development.
AB  - Intrathymic T cell development is predicated on the Notch1 ligand Delta-like
      (Dll) 4. However, both Dll4 and Dll1 can support T cell development in vitro.
      Endocytosis of Dll1 is important for Notch activation, whereas currently there is
      no evidence for the role of Dll4 endocytosis in T cell development. To elucidate
      this, we generated Dll4 constructs that modify or inhibit endocytosis. Our
      results show that targeting the intracellular domain affects Dll4's ability to
      induce Notch target gene expression, support efficient T cell development, and
      inhibit B cell development. Dll4 function relies on a combination of factors,
      which include strong Mindbomb1 (Mib1) association, ubiquitination, and
      internalization and recycling back to the cell surface, to engage Notch1
      effectively. Distinct membrane localization and the Delta/Serrate/Lag2 (DSL)
      domain were important for Dll4 function. These features are consistent with a
      "recycling" model, but not in opposition to a "mechano-transduction" model,
      whereby Dll4 is able to engage Notch and create a pulling force required to
      activate signaling, leading to the induction of T-lineage development. Taken
      together, in contrast to Dll1, Dll4 does not localize to lipid rafts and shows
      stronger association with Mib1 and increased Notch1 uptake, which likely account
      for its superior ability to induce T cell development.

PMID- 23162129
TI  - In vitro generation of long-lived human plasma cells.
AB  - Plasma cells (PCs), the terminal effectors of humoral immunity, are short-lived
      unless supported by niche environments in which they may persist for years. No
      model system has linked B cell activation with niche function to allow the in
      vitro generation of long-lived PCs. Thus, the full trajectory of B cell terminal
      differentiation has yet to be investigated in vitro. In this article, we describe
      a robust model for the generation of polyclonal long-lived human PCs from
      peripheral blood B cells. After a proliferative plasmablast phase, PCs persist in
      the absence of cell division, with viability limited only by elective culture
      termination. Conservative predictions for PC life expectancy are 300 d, but with
      the potential for significantly longer life spans for some cells. These long
      lived PCs are preferentially derived from memory B cells, and acquire a
      CD138(high) phenotype analogous to that of human bone marrow PCs. Analysis of
      gene expression across the system defines clusters of genes with related dynamics
      and linked functional characteristics. Importantly, genes in these
      differentiation clusters demonstrate a similar overall pattern of expression for
      in vitro and ex vivo PCs. In vitro PCs are fully reprogrammed to a secretory
      state and are adapted to their secretory load, maintaining IgG secretion of 120
      pg/cell/day in the absence of XBP1 mRNA splicing. By establishing a set of
      conditions sufficient to allow the development and persistence of mature human
      PCs in vitro, to our knowledge, we provide the first platform with which to
      sequentially explore and manipulate each stage of human PC differentiation.

PMID- 23162130
TI  - B lymphocyte-induced maturation protein-1 contributes to intestinal mucosa
      homeostasis by limiting the number of IL-17-producing CD4+ T cells.
AB  - The transcription factor B lymphocyte-induced maturation protein-1 (Blimp-1)
      plays important roles in embryonic development and immunity. Blimp-1 is required
      for the differentiation of plasma cells, and mice with T cell-specific deletion
      of Blimp-1 (Blimp-1CKO mice) develop a fatal inflammatory response in the colon.
      Previous work demonstrated that lack of Blimp-1 in CD4(+) and CD8(+) T cells
      leads to intrinsic functional defects, but little is known about the functional
      role of Blimp-1 in regulating differentiation of Th cells in vivo and their
      contribution to the chronic intestinal inflammation observed in the Blimp1CKO
      mice. In this study, we show that Blimp-1 is required to restrain the production
      of the inflammatory cytokine IL-17 by Th cells in vivo. Blimp-1CKO mice have
      greater numbers of IL-17-producing TCRbeta(+)CD4(+)cells in lymphoid organs and
      in the intestinal mucosa. The increase in IL-17-producing cells was not restored
      to normal levels in wild-type and Blimp-1CKO-mixed bone marrow chimeric mice,
      suggesting an intrinsic role for Blimp-1 in constraining the production of IL-17
      in vivo. The observation that Blimp-1-deficient CD4(+) T cells are more prone to
      differentiate into IL-17(+)/IFN-gamma(+) cells and cause severe colitis when
      transferred to Rag1-deficient mice provides further evidence that Blimp-1
      represses IL-17 production. Analysis of Blimp-1 expression at the single cell
      level during Th differentiation reveals that Blimp-1 expression is induced in Th1
      and Th2 but repressed by TGF-beta in Th17 cells. Collectively, the results
      described here establish a new role for Blimp-1 in regulating IL-17 production in
      vivo.

PMID- 23162131
TI  - Unlinked memory helper responses promote long-lasting humoral alloimmunity.
AB  - Essential help for long-lived alloantibody responses is theoretically provided
      only by CD4 T cells that recognize target alloantigen, processed and presented by
      the allospecific B cell. We demonstrate that in an alloresponse to multiple MHC
      disparities, cognate help for class-switched alloantibody may also be provided by
      CD4 T cells specific for a second "helper" alloantigen. This response was much
      shorter-lived than when help was provided conventionally, by Th cell recognition
      of target alloantigen. Nevertheless, long-lasting humoral alloimmunity developed
      when T cell memory against the helper alloantigen was first generated.
      Costimulatory blockade abrogated alloantibody produced through naive Th cell
      recognition of target alloantigen but, crucially, blockade was ineffective when
      help was provided by memory responses to the accessory helper alloantigen. These
      results suggest that memory Th cell responses against previously encountered
      graft alloantigen may be the dominant mechanism for providing help to generate
      new specificities of alloantibody in transplant patients receiving
      immunosuppression.

PMID- 23162132
TI  - Potent induction of antibody-secreting B cells by human dermal-derived CD14+
      dendritic cells triggered by dual TLR ligation.
AB  - Targeting CD14(+) dermal-derived dendritic cells (DDCs) is a rational approach
      for vaccination strategies aimed at improving humoral immune responses, because
      of their natural ability to stimulate naive B cells. In this study, we show that
      CD14(+) DDCs express mRNA for TLRs 1-9, but respond differentially to single or
      paired TLR ligands. Compared to single ligands, some combinations were
      particularly effective at activating CD14(+) DDCs, as shown by enhanced
      expression of B cell stimulatory cytokines (IL-6, IL-10, and TNF-alpha) and more
      pronounced phenotypic maturation. These combinations were resiquimod (R-848) plus
      polyinosinic-polycytidylic acid [Poly(I:C)], R-848 plus LPS, Pam3CSK4 plus
      Poly(I:C), and LPS plus Poly(I:C). We also found that selected TLR ligand pairs
      [R-848 plus either LPS or Poly(I:C)] were superior to individual agents at
      boosting the inherent capacity of CD14(+) DDCs to induce naive B cells to
      proliferate and differentiate into CD27(+) CD38(+) B cells that secrete high
      levels of IgG and IgA. When treated with the same TLR ligand combinations,
      CD14(+) DDCs also promoted the differentiation of Th1 (IFN-gamma-secreting)
      CD4(+) T cells, but not of Th2 or Th17 CD4(+) T cells. These observations may
      help to identify adjuvant strategies aimed at inducing protective immune
      responses to various pathogens, including but not limited to HIV-1.

PMID- 23162134
TI  - Vitamin D: an adjunct to antiretroviral therapy?

PMID- 23162133
TI  - Human papillomavirus genotype attribution and estimation of preventable fraction
      of anal intraepithelial neoplasia cases among HIV-infected men who have sex with
      men.
AB  - BACKGROUND: The prevention of human papillomavirus (HPV)-induced anal cancer in
      high-risk populations such as human immunodeficiency virus (HIV)-infected men who
      have sex with men (MSM) remains an urgent priority, given rising incidence rates
      despite widespread antiretroviral therapy use. METHODS: HPV genotypes and anal
      disease prevalence, by cytology and histopathologic findings, were evaluated
      among 363 HIV-infected MSM. We modeled fractions of high-grade anal
      intraepithelial neoplasia (HGAIN) attributable to individual carcinogenic HPV
      genotypes and estimated the range of the proportion of HGAIN cases potentially
      preventable by prophylactic HPV vaccines. RESULTS: HPV16 was the most common
      genotype overall (26.4% of cases) and among HGAIN cases (55%). Prevalence of
      multiple (>= 2) carcinogenic HPV genotypes increased from 30.9% in cases of AIN
      grade <1 to 76.3% in cases of AIN grade 3 (P(trend) < .001). The fractions of
      HGAIN cases attributable to carcinogenic HPV16/18 targeted by currently licensed
      bivalent and quadrivalent HPV vaccines ranged from 12% to 61.5%, and the
      fractions attributable to carcinogenic HPV16/18/31/33/45/52/58 targeted by an
      investigational nonavalent HPV vaccine ranged from 39% to 89.4%. CONCLUSIONS: Our
      analytical framework allows estimation of HGAIN cases attributable to individual
      HPV genotypes in the context of multiple concurrent HPV infections, which are
      very common among HIV-infected MSM. Our results suggest that licensed and
      investigational HPV prophylactic vaccines have the potential to prevent a
      substantial proportion of HGAIN cases in this population.

PMID- 23162135
TI  - Immunization of macaques with soluble HIV type 1 and influenza virus envelope
      glycoproteins results in a similarly rapid contraction of peripheral B-cell
      responses after boosting.
AB  - The envelope glycoproteins (Env) represent a critical component of a successful
      antibody-mediated human immunodeficiency virus type 1 (HIV-1) vaccine. However,
      immunization with soluble Env was reported to induce short-lived antibody
      responses, suggesting that Env has unusual immunogenic properties. Here, we
      directly compared the magnitude and durability of B-cell responses induced by HIV
      1 Env and an unrelated soluble viral protein, influenza virus hemagglutinin (HA),
      in simultaneously inoculated macaques. We demonstrate robust peak responses
      followed by rapid contraction of circulating antibody and memory B cells for both
      antigens, suggesting that short-lived responses are not unique to HIV-1 Env but
      may be a common feature of soluble protein vaccines.

PMID- 23162136
TI  - Impaired skeletal muscle microvascular function and increased skeletal muscle
      oxygen consumption in severe falciparum malaria.
AB  - BACKGROUND: Organ dysfunction and tissue hypoxia in severe falciparum malaria
      result from an imbalance between oxygen delivery and demand. In severe malaria,
      microvascular obstruction from parasite sequestration decreases oxygen delivery.
      However, host microvascular function (defined as the capacity to increase oxygen
      delivery in response to ischemia) and oxygen consumption have not been assessed.
      METHODS: We used near-infrared resonance spectroscopy to measure thenar muscle
      microvascular function (StO(2)recov) and oxygen consumption (VO(2)) in 36 adults
      in Papua, Indonesia, with severe malaria, 33 with moderately severe malaria
      (MSM), 24 with severe sepsis, and 36 healthy controls. RESULTS: In the severe
      malaria group, the StO(2)recov of 2.7%/second was 16% and 22% lower than that in
      the MSM group (3.1%/second) and control group (3.5%/second), respectively (P <
      .001), and comparable to that in the severe sepsis group (2.5%/second). In the
      severe malaria group, StO(2)recov was inversely correlated with lactate level (r
      = -0.63; P < .001) and predicted death (area under the receiver operating
      characteristic curve, 0.71 [95% confidence interval {CI}, .51-.92]), with each
      percentage decrease associated with an increased odds of mortality (odds ratio,
      2.49 [95% CI, 1.05-6.2]). Conversely, VO(2) increased in the severe malaria group
      by 18%, compared with levels in the control and severe sepsis groups (P < .001),
      and was associated with parasite biomass (r = 0.49; P = .04). CONCLUSIONS:
      Impaired microvascular function is associated with increased mortality among
      individuals with severe malaria, while oxygen consumption is increased. Tissue
      hypoxia may result not only from microvascular obstruction, but also from
      impaired ability of the microvasculature to match oxygen delivery to increased
      oxygen demand.

PMID- 23162137
TI  - Vitamin D status and incidence of pulmonary tuberculosis, opportunistic
      infections, and wasting among HIV-infected Tanzanian adults initiating
      antiretroviral therapy.
AB  - BACKGROUND: Maintaining vitamin D sufficiency may decrease the incidence of
      pulmonary tuberculosis and other infectious diseases. We present the first
      prospective study of vitamin D among human immunodeficiency virus (HIV)-infected
      adults receiving antiretrovirals in sub-Saharan Africa. METHODS: Serum 25
      hydroxyvitamin D (25(OH)D) level was assessed at antiretroviral therapy (ART)
      initiation for 1103 HIV-infected adults enrolled in a trial of multivitamins (not
      including vitamin D) in Tanzania. Participants were prospectively followed at
      monthly visits at which trained physicians performed a clinical examination and
      nurses took anthropometric measurements and assessed self-reported symptoms. Cox
      proportional hazards models estimated hazard ratios (HRs) of morbidity outcomes.
      RESULTS: After multivariate adjustment, vitamin D deficiency (defined as a
      concentration of <20 ng/mL) had a significantly greater association with incident
      pulmonary tuberculosis, compared with vitamin D sufficiency (HR, 2.89; 95%
      confidence interval [CI], 1.31-7.41; P = .027), but no association was found for
      vitamin D insufficiency (defined as a concentration of 20-30 ng/mL; P = .687).
      Deficiency was also significantly associated with incident oral thrush (HR, 1.96;
      95% CI, 1.01-3.81; P = .046), wasting (HR, 3.10; 95% CI, 1.33-7.24; P = .009),
      and >10% weight loss (HR, 2.10; 95% CI, 1.13-3.91; P = .019). Wasting results
      were robust to exclusion of individuals experiencing pulmonary tuberculosis.
      Vitamin D status was not associated with incident malaria, pneumonia, or anemia.
      CONCLUSIONS: Vitamin D supplementation trials for adults receiving ART appear to
      be warranted.

PMID- 23162138
TI  - Quinine treatment selects the pfnhe-1 ms4760-1 polymorphism in Malian patients
      with Falciparum malaria.
AB  - BACKGROUND: The mechanism of Plasmodium falciparum resistance to quinine is not
      known. In vitro quantitative trait loci mapping suggests involvement of a
      predicted P. falciparum sodium-hydrogen exchanger (pfnhe-1) on chromosome 13.
      METHODS: We conducted prospective quinine efficacy studies in 2 villages, Kolle
      and Faladie, Mali. Cases of clinical malaria requiring intravenous therapy were
      treated with standard doses of quinine and followed for 28 days. Treatment
      outcomes were classified using modified World Health Organization protocols.
      Molecular markers of parasite polymorphisms were used to distinguish recrudescent
      parasites from new infections. The prevalence of pfnhe-1 ms4760-1 among parasites
      before versus after quinine treatment was determined by direct sequencing.
      RESULTS: Overall, 163 patients were enrolled and successfully followed. Without
      molecular correction, the mean adequate clinical and parasitological response
      (ACPR) was 50.3% (n = 163). After polymerase chain reaction correction to account
      for new infections, the corrected ACPR was 100%. The prevalence of ms4760-1
      increased significantly, from 26.2% (n = 107) before quinine treatment to 46.3%
      (n = 54) after therapy (P = .01). In a control sulfadoxine-pyrimethamine study,
      the prevalence of ms4760-1 was similar before and after treatment. CONCLUSIONS:
      This study supports a role for pfnhe-1 in decreased susceptibility of P.
      falciparum to quinine in the field.

PMID- 23162139
TI  - Who wants food? Individual characteristics in raven yells.
AB  - Discriminating between different individuals is considered as prerequisite for
      any forms of social knowledge. In birds, discriminating between conspecifics
      based on individual characteristics has been tested mainly in the auditory domain
      with territorial calls and songs for neighbour and kin discrimination but little
      is known about discriminating between signallers in food calls. Ravens utilize a
      large set of calls and show individually distinctive call repertoires. Moreover,
      they show advanced social tactics during foraging, suggesting that they are
      capable of dealing with conspecifics on an individual basis. When confronted with
      food that is difficult to access, ravens produce particular calls ('haa', yells);
      these calls attract other ravens and, thus, have been hypothesized to serve as
      'functionally referential signals'. We here examined whether ravens are able to
      differentiate between individuals on the basis of these food calls. We first
      analysed individual differences in call parameters, using 424 food calls recorded
      from 18 individually marked wild ravens in the Austrian Alps. We then tested 18
      captive ravens for recognition of individual differences in food calls with
      playbacks, using a habituation-dishabituation design. We found evidence that food
      calls show individual call characteristics in fundamental frequency and intensity
      related measurements providing ravens with the opportunity to respond according
      to these individually distinct features. Furthermore, ravens discriminated
      between unfamiliar ravens in the habituation-dishabituation experiment,
      indicating that they may discern individual differences. Our results suggest that
      raven food calls are individually distinct and that the birds may be capable of
      differentiating between food-calling individuals.

PMID- 23162140
TI  - Distal radioulnar joint injuries.
AB  - Distal radioulnar joint is a trochoid joint relatively new in evolution. Along
      with proximal radioulnar joint, forearm bones and interosseous membrane, it
      allows pronosupination and load transmission across the wrist. Injuries around
      distal radioulnar joint are not uncommon, and are usually associated with distal
      radius fractures,fractures of the ulnar styloid and with the eponymous Galeazzi
      or Essex_Lopresti fractures. The injury can be purely involving the soft tissue
      especially the triangular fibrocartilage or the radioulnar ligaments. The
      patients usually present with ulnar sided wrist pain, features of instability, or
      restriction of rotation. Difficulty in carrying loads in the hand is a major
      constraint for these patients. Thorough clinical examination to localize point of
      tenderness and appropriate provocative tests help in diagnosis. Radiology and MRI
      are extremely useful, while arthroscopy is the gold standard for evaluation. The
      treatment protocols are continuously evolving and range from conservative,
      arthroscopic to open surgical methods. Isolated dislocation are uncommon. Basal
      fractures of the ulnar styloid tend to make the joint unstable and may require
      operative intervention. Chronic instability requires reconstruction of the
      stabilizing ligaments to avoid onset of arthritis. Prosthetic replacement in
      arthritis is gaining acceptance in the management of arthritis.

PMID- 23162141
TI  - Osseous integration in porous tantalum implants.
AB  - Porous tantalum is a biomaterial that was recently introduced in orthopedics in
      order to overcome problems related to implant loosening. It is found to have
      osteoconductive, and possibly, osteoinductive properties hence useful in
      difficult cases with severe bone defects. So, it is of great interest to shed
      light on the mechanisms through which this material leads to new bone formation,
      after being implanted. Porous tantalum is biologically relatively inert, with
      restricted bonding capacity to the bone is restricted. In order to overcome this
      obstacle, it undergoes thermal processing in an alkaline environment. This
      process leads to extensive hydroxyapatite formation on its surface, and thus, to
      better integration of porous tantalum implants. Apart from this, new bone tissue
      formation occurs inside the pores of the porous tantalum after its implantation
      and this new bone retains the characteristics of the normal bone, that is, bone
      remodeling and Haversian systems formation. This finding is enhanced by the
      observation that porous tantalum is an appropriate substrate for osteoblast
      adherence, proliferation, and differentiation. Furthermore, the finding that
      osteoblasts derived from old women (> 60 years old) and cultivated on porous
      tantalum may grow faster than osteoblasts taken from younger women (< 45 years
      old) and cultivated on other substrates, can partially explain porous tantalum's
      good performance in cases of patients with severe bone defects. In conclusion,
      porous tantalum's chemical and mechanical properties are those that probably
      define the already noticed good performance of this material. However, further
      research is needed to totally clarify the mechanisms.

PMID- 23162143
TI  - Biomechanical analysis of the impact of fibular osteotomies at tibiotalar joint:
      A cadaveric study.
AB  - BACKGROUND: Osteotomy of the fibula is a common orthopedic procedure performed
      for various indications, including harvesting fibula for grafting purposes. The
      effect of fibular osteotomy and need for tibiofibular syndesmotic fixation fusion
      at different levels on tibiotalar joint is matter of debate. We performed a
      biomechanical analysis of the impact of fibular osteotomies at different levels
      and whether the fixation of distal tibiofibular joint mitigates instability
      caused by the osteotomy. MATERIALS AND METHODS: Six lower limb specimens from
      fresh adult cadavers were used to prepare leg-foot models. The specimens were
      assigned to six status according to the level of osteotomy and whether fixation
      of distal tibiofibular joint was performed or not. Each specimen was then loaded
      axially to 700 N by the material testing machine, and the tibiotalar joint
      contact area and peak pressure were measured using an electronic pressure sensor.
      RESULTS: The contact area and the pressure of tibiotalar joint showed significant
      changes when compared to the normal specimen. All osteotomy specimens had a
      decreased tibiotalar contact area and an increased peak pressure. This positively
      correlated with proximity of level of osteotomy to the lateral malleolus.
      CONCLUSIONS: Through this study, we found that fibular osteotomy had an adverse
      effect in terms of decreasing the contact surface of tibiotalar joint that led to
      increased peak pressure in the joint. However, bone fusion and screw fixation of
      the distal tibiofibular joint reduced these adverse effects.

PMID- 23162142
TI  - Impact of Partial and complete rupture of anterior cruciate ligament on medial
      meniscus: A cadavaric study.
AB  - BACKGROUND: The clinical relationship between medial meniscus tear and anterior
      cruciate ligament (ACL) rupture has been well documented. However, the mechanism
      of this clinical phenomenon is not exactly explained. Our aim is to investigate
      the biomechanical impact of partial and complete ACL rupture on different parts
      of medial meniscus. MATERIALS AND METHODS: TWELVE FRESH HUMAN CADAVERIC KNEE
      SPECIMENS WERE DIVIDED INTO FOUR GROUPS: ACL intact (ACL-I), anteromedial bundle
      transection (AMB-T), posterolateral bundle transection (PLB-T), and ACL complete
      transection (ACL-T) group. Strain on the anterior horn, body part, and posterior
      horn of medial meniscus were measured under 200 N axial compressive tibial load
      at 0 degrees , 30 degrees , 60 degrees , and 90 degrees  of knee flexion,
      respectively. RESULTS: Compared with the control group (ACL-I), the ACL-T group
      had a higher strain on whole medial meniscus at 0 degrees , 60 degrees , and 90
      degrees  of flexion. But at 30 degrees , it had a higher strain on posterior horn
      of meniscus only. As to PLB-T group, strain on whole meniscus increased at full
      extension, while strain increased on posterior horn at 30 degrees  and on body of
      meniscus at 60 degrees . However, AMB-T only brought about higher strain at 60
      degrees  of flexion on body and posterior horn of meniscus. CONCLUSIONS: Similar
      to complete rupture, partial rupture of ACL can also trigger strain concentration
      on medial meniscus, especially posterior horn, which may be a more critical
      reason for meniscus injury associated with chronic ACL deficiency.

PMID- 23162144
TI  - Medial proximal tibial angle after medial opening wedge HTO: A retrospective
      diagnostic test study.
AB  - BACKGROUND: Medial proximal tibial angle (MPTA) is the commonly used angle, which
      is simply measured from the knee radiographs. It can determine the correction
      angle in medial opening wedge high tibial osteotomy (MOWHTO). The hypothesis of
      our study is that post-osteotomy MPTA can predict the change in correction angle,
      and we aimed to determine the optimal MPTA with which to prevent recurrent varus
      deformity after MOWHTO. MATERIALS AND METHODS: Between January 2002 and April
      2010, radiographs of 59 patients, who underwent 71 MOWHTOs using the locking
      compression osteotomy plates without bone grafts, were evaluated for the change
      of the MPTA. The MPTA was measured preoperatively and one and twelve months
      postoperatively. The changes of MPTA between one and twelve months were
      classified into valgus, stable, and varus change. The predicting factors were
      analyzed using analysis of variance (ANOVA) and Bonferroni multiple comparisons.
      The receiver operating characteristic (ROC) curve was used to find out the cut
      off point for preventing the recurrent varus deformity. RESULTS: The overall
      preoperative, and one and twelve month postoperative MPTA values were 84.4 +/-
      2.4 degrees , 97.2 +/- 4.1 degrees , and 96.3 +/- 3.6 degrees , respectively.
      Between one and twelve months, 39 knees displayed reduced varus change (-2.8 +/-
      2.1 degrees ), 18 knees displayed no change, and 14 knees displayed a greater
      valgus change (+2.9 +/- 2.1 degrees ). The best factor for predicting these
      changes was the one month MPTA value (P = 0.006). By using the ROC curve, a one
      month MPTA of 95 degrees  was analyzed as the cut off point for preventing the
      recurrent varus deformity. With MPTA >=95 degrees , 92.3% of the osteotomies
      exhibited stable or varus change and 7.7% exhibited valgus change. However, with
      MPTA <95 degrees , 47.4% exhibited stable or varus change and 52.6% exhibited
      valgus change (P < 0.001, odds ratio = 13.3). CONCLUSION: The postoperative MPTA
      can be used to predict the change in correction angle and an MPTA of at least 95
      degrees  is the crucial angle with which to prevent recurrent varus deformity.

PMID- 23162145
TI  - Use of amplified Mycobacterium tuberculosis direct test (Gen-probe Inc., San
      Diego, CA, USA) in the diagnosis of tubercular synovitis and early arthritis of
      knee joint.
AB  - BACKGROUND: The diagnosis of knee joint tuberculosis, especially in early stages
      of synovial disease, has more often been based on clinicoradiological suspicion,
      with no single test claiming to be a dependable rapid diagnostic test with high
      sensitivity and specificity. Nuclear amplification tests in vogue like the
      polymerase chain reaction have shown variable sensitivity and false positivity
      rates in various studies. We evaluated the role of Amplified Mycobacterium
      tuberculosis Direct Test (AMTDT) or Genprobe in the diagnosis of knee joint
      tuberculosis in early, especially, early synovitis and arthritis cases. PATIENTS
      AND METHODS: Thirty two patients of suspected knee joint tuberculosis were
      subjected to diagnostic arthroscopy during the study period. The synovial fluid
      and tissue were subjected to mycobacterial culture, histopathology, and AMTDT. A
      comparative analysis of the sensitivity and specificity of this new test with
      culture and histopathology was done and the time taken for reporting was
      calculated for each test. RESULTS: Out of 32 tissue samples, 8 were found to be
      positive with mycobacterial culture [Lowenstein Jensen (LJ)/Bactec], 11 were
      positive with histopathology, and 5 were found to positive with AMTDT. The
      sensitivity of AMTDT was found to be 62.5% and specificity was 100% with a P
      value of 0.083. The results were obtained earliest with AMTDT with a mean
      reporting time of 1.2 days, while the results of histopathology were obtained in
      a mean time of 6.8 days, BacT alert in 22.5 days, and conventional LJ medium
      culture results in 48.6 days. CONCLUSION: AMTDT or Genprobe is a rapid diagnostic
      test for early diagnosis of tubercular arthritis, but has low sensitivity in knee
      joint tuberculosis. Nuclear amplification tests are still far from being a single
      promising alternative to conventional tests in cases of joint tuberculosis.
      Routine use of arthroscopic biopsies in all suspected cases is helpful in the
      early diagnosis of knee joint tuberculosis.

PMID- 23162146
TI  - Outcome of dorsolumbar vertebral hemangiomas presenting with neuraxial
      compression.
AB  - BACKGROUND: Hemangiomas are benign vascular tumors associated with proliferation
      of blood vessels in bone or soft tissue and they are usually incidental findings
      in vertebrae. When symptomatic, they present with features of radiculopathy,
      myelopathy, or vertebral fractures. Treatment options are varied, include sole
      embolization, embolization combined with surgical excision, surgical excision
      alone, percutaneous ablation, and radiotherapy. We hereby describe a series of
      seven cases of symptomatic vertebral hemangiomas operated from 2006 to 2009.
      MATERIALS AND METHODS: Their clinical and radiological profile and outcome have
      been described. All patients were subjected to surgical excision followed by
      instrumentation. Outcome was assessed at a followup of 2 years following surgery
      with Frankel grading system. RESULTS: Seven patients (five females and two males)
      were included in the study. The mean age was 33.85 years with the mean duration
      of symptoms of 12 months. All seven cases were symptomatic vertebral hemangiomas
      with cord compression and underwent surgical excision. Preoperatively, patients
      with poor Frankel grade such as A and B improved postoperatively to C, D, or E.
      CONCLUSION: Surgical excision of these lesions is difficult due to the tremendous
      amount of intraoperative bleeding. During surgery, brisk bleeding is usually
      encountered, but can be brought under control with adequate preoperative
      preparation and expertize. Preoperative embolization may help to reduce the
      bleeding, but at times it may be difficult to do if vertebrae are replaced by a
      solid hard mass. In spite of the risks associated with surgery, it still is the
      treatment of choice as a single intervention, especially in aggressive vertebral
      hemangiomas.

PMID- 23162147
TI  - Role of calf muscle stimulation in the prevention of DVT in Indian patients
      undergoing surgeries for fractures around the hip.
AB  - BACKGROUND: The venous stasis of soleal vein during surgery may be an important
      factor in the development of deep vein thrombosis (DVT). The stimulation of calf
      muscle during surgery may help in preventing DVT. The present study is conducted
      to evaluate the role of peroperative calf muscle electrostimulation in prevention
      of DVT in patients undergoing surgeries around the hip joint. MATERIALS AND
      METHODS: The study comprised 200 patients undergoing surgeries around the hip
      joint. The patients having risk factors (such as previous myocardial infarction,
      malignancies, paraplegia or lower limb monoplegia, previous history of DVT or
      varicose veins, etc.) for the development of DVT were excluded. They were
      randomized into two groups: 100 cases were given peroperative calf muscle
      electrostimulation for DVT prophylaxis (Group A) and the remaining 100 patients
      were taken as controls without any prophylaxis (Group B). The color Doppler
      ultrasound was performed to exclude pre-existing DVT and on 7(th) day
      postoperative to find out the incidence of DVT in both the groups. RESULTS: Two
      patients among Group A and six patients among Group B demonstrated DVT on
      ultrasonography, but the difference was not found to be statistically significant
      (P=0.279). None of the patients had any clinical evidence of DVT. CONCLUSION: The
      role of peroperative calf muscle electrostimulation for DVT prophylaxis remains
      controversial. The risk of developing DVT in patients undergoing surgeries around
      the hip joint is very less in patients analysed in our series.

PMID- 23162148
TI  - Outcome of one-stage treatment of developmental dysplasia of hip in older
      children.
AB  - BACKGROUND: The principles of treatment of congenital dislocation of hip in old
      children are different than those of infants and neonates. The purpose of this
      study is to evaluate the radiographic and functional results of one-stage
      treatment (open reduction, femoral shortening derotation, and Salter's osteotomy)
      of DDH in older children. MATERIALS AND METHODS: Between January 2005 and June
      2010, 25 patients (30 hips) underwent one-stage triple procedure of open
      reduction, femoral shortening derotation, and Salter's osteotomy for the
      treatment of DDH. Preoperatively, they were classified according to the Tonnis
      class. Clinical outcomes were assessed using the modified McKay's criteria to
      measure pain symptoms, gait pattern, Trendelenburg sign status, and the range of
      hip joint movement. Radiographic assessment was made using Severin's scoring
      method to measure the centre-edge angle and dysplasia. RESULTS: The mean age at
      the time of operation was 3.9 years (range 1.6-8 years), and the average duration
      of followup was 4.1 years (range 2-7.6 years). The McKay's score was excellent in
      13 hips, good in 14 hips, fair in 2, and poor in 1 hip. The Severin's class I and
      II was found in 25 (83.3%) hips at the time of final evaluation as compared to
      none at the time of presentation. CONCLUSIONS: Young children having DDH can
      safely be treated with an extensive one-stage triple procedure of open reduction,
      femoral shortening derotation, and Salter's osteotomy, without increasing the
      risk of AVN. Early diagnosis and intervention is the successful treatment of
      patients suffering from DDH.

PMID- 23162149
TI  - Results of proximal femur nail antirotation for low velocity trochanteric
      fractures in elderly.
AB  - BACKGROUND: The proximal femur nail antirotation (PFNA) is the recent addition to
      the growing list of intramedullary implants for trochanteric fracture fixation.
      The initial results in biomechanical and clinical studies have shown promise. We
      report our results of low velocity trochanteric fractures internally fixed by
      proximal femur nail antirotation. MATERIALS AND METHODS: A prospective study was
      conducted to assess the results of 122 elderly patients with low velocity
      trochanteric fractures [39 - stable (AO; 31-A1) and 83 - unstable (AO; 31-A2 and
      A3)] treated with PFNA from December 2008 to April 2010. Followup functional and
      radiological assessments were done. Results obtained were compared between stable
      and unstable fracture patterns using statistical tools. RESULTS: The mean
      followup was 21 months (12-28 months). 11 patients were lost in followup. Union
      was achieved in all but one patient. Varus collapse was seen in 14 patients and
      helical blade cut out in one patient. Stable and satisfactorily reduced fractures
      had a significantly better radiological outcome. Functional outcome measures were
      similar across fracture patterns. 65% of the patients returned to their preinjury
      status. The overall complication rate was also significantly higher in unstable
      fractures. CONCLUSION: Good results with relatively low complication rates can be
      achieved by PFNA in trochanteric fractures in the elderly. Attention to implant
      positioning, fracture reduction and a good learning curve is mandatory for
      successful outcomes.

PMID- 23162150
TI  - Arthroscopic management of mucoid degeneration of anterior cruciate ligament.
AB  - BACKGROUND: Mucoid degeneration of the anterior cruciate ligament (ACL) is a less
      understood entity. The purpose of this study was to diagnose mucoid degeneration
      of anterior cruciate ligament and to assess the effectiveness of arthroscopic
      treatment in these patients. MATERIALS AND METHODS: Between December 2007 and
      November 2011, 20 patients were diagnosed to be suffering from mucoid
      degeneration of anterior cruciate ligament (ACL) on the basis of magnetic
      resonance imaging (MRI), histopathology, and arthroscopy findings. 12 patients
      were males and 8 patients were females, with mean age of 42.2 years for males
      (range 28-52 years) and 39.4 years for females (range 30-54 years). They
      presented with pain on terminal extension (n=10) and on terminal flexion (n=2)
      without history of significant preceding trauma. MRI showed an increased signal
      in the substance of the ACL both in the T1- and T2-weighted images, with a mass
      like configuration that was reported as a partial or complete tear of the ACL by
      the radiologist. At arthroscopy, the ACL was homogenous, bulbous, hypertrophied,
      and taut, occupying the entire intercondylar notch. A debulking of the ACL was
      performed by a judicious excision of the degenerated mucoid tissue, taking care
      to leave behind as much of the intact ACL as possible. Releasing it and
      performing a notchplasty treated impingement of the ACL to the roof and lateral
      wall. In one patient, we had to replace ACL due to insufficient tissue left
      behind to support the knee. RESULTS: Good to excellent pain relief on terminal
      flexion-extension was obtained in 19 of 20 knees. The extension deficit was
      normalized in all knees. Lachman and anterior drawer test showed a firm endpoint
      in all, and 85% (n=17) showed good to excellent subjective satisfaction.
      CONCLUSIONS: Mucoid hypertrophy of the ACL should be suspected in elderly persons
      presenting pain on terminal extension or flexion without preceding trauma,
      especially when there is no associated meniscal lesion or ligamentous
      insufficiency. They respond well to a judicious arthroscopic release of the ACL
      with notchplasty.

PMID- 23162151
TI  - A retrospective analysis of risk factors for meniscal co-morbidities in anterior
      cruciate ligament injuries.
AB  - BACKGROUND: The association of meniscal cartilage injury with anterior cruciate
      ligament (ACL) injury is well documented in literature. The aim of this study was
      to examine the relative risk factors for meniscal pathology at the time of
      arthroscopic ACL reconstruction. MATERIALS AND METHODS: A review of the case
      records including both in-patient and out-patient charts of all patients who
      underwent arthroscopic ACL reconstruction during the preceding 3 years was
      performed by either of the authors. The relative incidences of associated
      meniscal pathologies were analyzed in correlation with age, side of injury, time
      to surgery, mode of injury, and gender as the risk factors. Statistical analysis
      was performed to obtain individual data correlation. RESULTS: A total of 192
      patients underwent ACL reconstruction during the 3-year time frame. Of these,
      complete data sets were available for 129 patients. Analysis revealed that the
      only factor that was statistically significant in raising the risk of meniscal
      pathology was the time to surgery (P = 0.001). There was a significant increase
      in medial, lateral, and both meniscal tears noted in cases operated beyond 24
      weeks. Further, the incidence of medial meniscal tears as well as lateral
      meniscal tears increased with delay in presentation for surgery (P = 0.004). Mode
      of injury, age at presentation, sex, and side were not significantly associated
      with an increased incidence of meniscal pathology. CONCLUSION: The single factor
      that significantly affects incidence of meniscal co-morbidity in ACL injury is
      the delay in presentation (i.e. the time to surgery). The incidence of lateral
      meniscal tears as well as medial meniscal tears increased with delay in surgery.
      This should guide us toward recommending all patients irrespective of age,
      gender, or mode of injury to undergo early reconstruction, thereby reducing the
      likelihood of developing meniscal pathology.

PMID- 23162152
TI  - Outcome of complex tibial plateau fractures treated with external fixator.
AB  - BACKGROUND: Tibial plateau fractures are usually associated with communition and
      soft tissue injury. Percutaneous treatment of these complex fractures is intended
      to reduce soft issue complications and postoperative stiffness of the knee joint.
      We assessed the complications, clinical outcome scores, and postoperative knee
      range of movements, after fluoroscopic assisted closed reduction and external
      fixator application. MATERIALS AND METHODS: Seventy eight complex tibial plateau
      fractures in 78 patients were included in the study. All fractures were managed
      with closed reduction and external fixator application. In 28 cases with
      intraarticular split, we used percutaneous cancellous screw fixation for
      reduction and fixation of condylar parts. In nine open fractures, immediate
      debridement was done. In 16 cases, elevation of depressed segment and bone
      grafting was required, which was done from a very small incision. All patients
      were clinically and radiographically evaluated at a mean followup of 26.16 months
      (range 6-60 months). RESULTS: Clinical results were evaluated according to the
      Rasmussen's criteria. Average healing time was 13.69 weeks (range 12- 28 weeks).
      Mean knee range of motion was 122.60 degrees  (range 110 degrees -130 degrees ).
      Forty seven results were scored as excellent, 25 good, 2 fair, and 1 as poor.
      CONCLUSION: We believe that minimally invasive treatment by percutaneous
      techniques and external fixation is a fairly reasonable treatment alternative, if
      near anatomical reduction of joint surface can be confirmed on fluoroscopy.

PMID- 23162153
TI  - Hamstring transfer for quadriceps paralysis in post polio residual paralysis.
AB  - CONTEXT: Paralysis of quadriceps muscle leads to severe disability as the knee is
      unstable and cannot be fully extended and locked in extension, which results in
      giving way of the knee joint. Because of this, the patient tries to get stability
      of the knee by various means like hand to knee gait, extreme internal or external
      rotation of the affected limb to stabilize knee by support of medial or lateral
      collateral ligament, respectively, or by tilting pelvis. When there is
      concomitant weakness of gluteus maximus quadriceps and hamstrings (MRC muscle
      power less than grade III), patient may develop compensatory hyperlordosis of
      spine. Hamstring (H) transfer is a well-accepted procedure for patients with
      quadriceps (Q) weakness. For hamstring transfer, we have used a modified
      technique of anchoring of biceps femoris and semitendinosus tendon to patella.
      Instead of cutting the periosteum over the patella in an I-shaped manner, an
      osteoperisoteal flap was raised after two parallel incisions over the patella and
      both tendons were sutured under the flap with each other. We conducted a
      retrospective evaluation of the results of modified hamstring transfer in 267
      patients of post polio residual paralysis with residual quadriceps paralysis.
      MATERIALS AND METHODS: Two hundred and fifty young patients (100 male and 150
      female patients) who had quadriceps paralysis due to polio were managed by
      hamstring transfer at a single center between 1984 and 1996 and were followed for
      a mean of 5 years (range 4-12 years). Age of patients ranged from 7 to 18 years
      in 238 patients and 12 patients were above the age of 18 years. All cases were
      followed periodically, and assessment of knee extension, extension lag, knee
      flexion, elimination of calliper, and avoidance of hand to knee gait was done.
      RESULTS: One hundred and sixty two patients (65%) showed excellent results, 38
      patients (15%) had good results, and 50 patients (20%) showed poor results.
      Ninety three patients had major complications like genu recurvatum, restricted
      knee flexion, and extension lag. Ten patients had minor complications like
      superficial infection and epidermal edge necrosis. CONCLUSIONS: H to Q transfer
      in the presence of quadriceps paralysis with good power in hamstring is a better
      alternative than supracondylar osteotomy because it is a dynamic correction and
      it produces some degree of recurvatum with increasing stability of knee in
      extension while walking. While inserting hamstring over patella the periosteum is
      not cut in an I-shaped fashion to create a flap which gives additional strength
      to new insertion and also patella act as a fulcrum during the extension of knee
      by producing the bowstring effect.

PMID- 23162154
TI  - Neglected locked vertical patellar dislocation.
AB  - Patellar dislocations occurring about the vertical and horizontal axis are rare
      and irreducible. The neglected patellar dislocation is still rarer. We describe
      the clinical presentation and management of a case of neglected vertical patellar
      dislocation in a 6 year-old boy who sustained an external rotational strain with
      a laterally directed force to his knee. Initially the diagnosis was missed and 2
      months later open reduction was done. The increased tension generated by the
      rotation of the lateral extensor retinaculum kept the patella locked in the
      lateral gutter even with the knee in full extension. Traumatic patellar
      dislocation with rotation around a vertical axis has been described earlier, but
      no such neglected case has been reported to the best of our knowledge.

PMID- 23162155
TI  - Traumatic proximal tibiofibular dislocation with neurovascular injury.
AB  - 23 years old male presented with inferolateral dislocation of proximal
      tibiofibular joint associated with popliteal artery and common peroneal nerve
      injury. The extension of the injury to involve the interosseus membrane up to the
      distal tibiofibular joint. The association of popliteal artery injury is not
      reported before to the best of our knowledge.

PMID- 23162157
TI  - Bipolar physeal injuries of the clavicle in a child.
AB  - This article reports a type II Salter and Harris injury at either ends of the
      clavicle in a 13-year-old child with postero-inferior displacement at the lateral
      and antero-superior displacement at the medial end of the clavicle shaft. He was
      treated in a shoulder immobilizer. The mechanism of injury is postulated as
      pivoting of the clavicle on the first rib with shearing at either ends leading to
      a bipolar injury. The brachial plexus and subclavian vessels are at a risk of
      damage at the pivot as they lie in close vicinity to the first rib. In view of
      the intact periosteal sleeve as well as joint articulation at both ends, the
      fracture healed with no functional loss.

PMID- 23162156
TI  - Atypical metatarsal fracture in a patient on long term bisphosphonate therapy.
AB  - A 24 years old female of cushing disease had undergone adrenelectomy. She was put
      on alendronate and steroid. After six and a half years she developed pathological
      fracture subtrochanteric femur. The patient was treated with proximal femoral
      nailing and the fracture united. 2 years later she developed pain right foot. She
      was diagnosed as transverse fracture of fifth metatarsal. We report this rare
      case of atypical metatarsal fracture in a patient on long term bisphosphonate
      therapy.

PMID- 23162158
TI  - Intrathoracic displacement of the humeral head in a trauma patient.
AB  - Fracture and intrathoracic displacement of the humeral head is the result of
      severe high energy trauma and are extremely rare. Because of the exceedingly
      limited number of cases, appropriate treatment modality remains unclear.
      Hitherto, we describe a unique case of thoracic aorta injury caused by fragmented
      humeral head. Purposeful medical examination and fast locating of the humeral
      head fragment are crucial for the selection of appropriate treatment modality.
      Early aggressive intervention, e.g., emergency thoracoscopy exploring, can be
      performed to treat potential thoracic complications.

PMID- 23162159
TI  - Synovitis of the wrist joint caused by an intraarticular perforation of an
      osteoid osteoma of the scaphoid.
AB  - Uncommon location and atypical presentation of the osteoid osteomas of the
      scaphoid can pose a diagnostic challenge. Because of its intraarticular location,
      scaphoid osteoid osteoma can present with synovitis which is the more commonly
      reported presentation for other intraarticular locations like in hip and elbow
      and only rarely reported at the wrist. We report a case of perforation of the
      osteoid osteoma into the wrist joint, resulting in exuberant synovitis. The
      clinical significance of this report is to reinforce that synovitis can be a
      presentation of osteoid osteoma and it should be considered in the differential
      diagnosis of monoarticular arthritis. Prolonged synovitis may cause damage to the
      other joint surfaces of the wrist and hence carpal osteoid osteoma should be
      considered for early surgical excision.

PMID- 23162160
TI  - Utility of combined hip abduction angle for hip surveillance in children with
      cerebral palsy.

PMID- 23162161
TI  - Cementless bipolar hemiarthroplasty in femoral neck fractures in elderly.

PMID- 23162162
TI  - Interaction of Biphenyl-Functionalized Eu(2+)-Containing Cryptate with Albumin:
      Implications to Contrast Agents in Magnetic Resonance Imaging.
AB  - The influence of albumin on the efficacy of a Eu(2+)-containing complex capable
      of interacting with human serum albumin (HSA) was investigated at different field
      strengths (1.4, 3, 7, 9.4, and 11.7 T). Relaxometric measurements indicated that
      the presence of albumin at higher field strengths (>3 T) did not result in an
      increase in the relaxivity of the Eu(2+) complex, but a relaxation enhancement of
      171 +/- 11% was observed at 1.4 T. Titration experiments using different
      percentages (2, 4.5, 6, 10, 15, and 25% w/v) of HSA and variable-temperature
      (17)O NMR measurements were performed to understand the effect of albumin on the
      molecular properties of the biphenyl-functionalized Eu(2+) complex that are
      relevant to magnetic resonance imaging.

PMID- 23162163
TI  - A fast, simple and robust protocol for growing crystals in the lipidic cubic
      phase.
AB  - A simple and inexpensive protocol for producing crystals in the sticky and
      viscous mesophase used for membrane protein crystallization by the in meso method
      is described. It provides crystals that appear within 15-30 min of setup at 293
      K. The protocol gives the experimenter a convenient way of gaining familiarity
      and a level of comfort with the lipidic cubic mesophase, which can be daunting as
      a material when first encountered. Having used the protocol to produce crystals
      of the test protein, lysozyme, the experimenter can proceed with confidence to
      apply the method to more valuable membrane (and soluble) protein targets. The
      glass sandwich plates prepared using this robust protocol can further be used to
      practice harvesting and snap-cooling of in meso-grown crystals, to explore
      diffraction data collection with mesophase-embedded crystals, and for an
      assortment of quality control and calibration applications when used in
      combination with a crystallization robot.

PMID- 23162165
TI  - The three-class ideal observer for univariate normal data: Decision variable and
      ROC surface properties.
AB  - Although a fully general extension of ROC analysis to classification tasks with
      more than two classes has yet to be developed, the potential benefits to be
      gained from a practical performance evaluation methodology for classification
      tasks with three classes have motivated a number of research groups to propose
      methods based on constrained or simplified observer or data models. Here we
      consider an ideal observer in a task with underlying data drawn from three
      univariate normal distributions. We investigate the behavior of the resulting
      ideal observer's decision variables and ROC surface. In particular, we show that
      the pair of ideal observer decision variables is constrained to a parametric
      curve in two-dimensional likelihood ratio space, and that the decision boundary
      line segments used by the ideal observer can intersect this curve in at most six
      places. From this, we further show that the resulting ROC surface has at most
      four degrees of freedom at any point, and not the five that would be required, in
      general, for a surface in a six-dimensional space to be non-degenerate. In light
      of the difficulties we have previously pointed out in generalizing the well-known
      area under the ROC curve performance metric to tasks with three or more classes,
      the problem of developing a suitable and fully general performance metric for
      classification tasks with three or more classes remains unsolved.

PMID- 23162164
TI  - Ethnicity, gender socialization, and children's attitudes towards gay men and
      lesbian women.
AB  - The aim of the present study was to assess whether children's attitudes towards
      gay men and lesbian women differ in relation to their ethnic backgrounds, and
      whether ethnic differences are a result of perceived differential gender
      socialization practices. Data were collected from children in eight Dutch
      elementary schools by means of a paper-and-pencil questionnaire administered in
      the classroom. All children (mean age 11.47; N = 229) lived in the Netherlands;
      50.2% had non-Western and 49.8% Western ethnic backgrounds. Children with non
      Western ethnic backgrounds reported more negative attitudes towards gays and
      lesbians. These children perceived more parental pressure to behave in accordance
      with their gender and showed more negative attitudes towards gender-nonconforming
      behaviour by peers. Hierarchical regression analyses revealed that cultural
      differences in attitudes towards gay men and lesbian women are partly mediated by
      differentially perceived parental pressure to behave in accordance with their
      gender.

PMID- 23162166
TI  - Phosphaalkenylidene bridged ferrocenes.
AB  - The lithiation of ferrocenylphosphane Fc-PH(2) (Fc = -C(5)H(4)FeC(5)H(5)) has
      been reinvestigated and both Fc-PHLi and Fc-PLi(2) have been identified by NMR
      spectroscopy. The lithiated phosphanides have been converted to the corresponding
      mono and bis(silylated) species the latter of which gave synthetic access to an
      oligomer in which three ferrocene units are symmetrically connected by
      phosphaalkene units. The charge distribution within this oligomer and its isomers
      has been analyzed using DFT calculations which indicates that the iron atom of
      the central metallocene unit is slightly more positive than the terminal ones.
      These findings are supported experimentally by Mobetabauer spectroscopy and
      cyclic voltammetry.

PMID- 23162167
TI  - Stress Reduction and T(g) Enhancement in Ternary Thiol-Yne-Methacrylate Systems
      via Addition-fragmentation Chain Transfer.
AB  - Since polymerization-induced shrinkage stress is detrimental in many
      applications, addition-fragmentation chain transfer (AFCT) was employed to induce
      network relaxation and adaptation that mitigate the shrinkage stress. Here, to
      form high glass transition temperature, high modulus polymers while still
      minimizing stress, multifunctional methacrylate monomers were incorporated into
      allyl sulfide-containing thiol-yne resins to provide simultaneously high glass
      transition temperatures and a facile mechanism for AFCT throughout the network.
      As a negative control, in an attempt to isolate just the effects of AFCT in the
      polymerization, a propyl sulfide-based diyne, which has a nearly identical
      chemical structure though absent any AFCT-capable functional group, was
      synthesized and implemented in place of the allyl sulfide-based diyne. The glass
      transition temperature of the ternary systems increased from 39 degrees C to 79
      degrees C as the methacrylate content increased while the shrinkage stress of the
      optimal ternary resin was lower than either the binary thiol-yne resin or the
      pure methacrylate resin. The stress relaxation benefit associated with AFCT
      increased with increasing allyl sulfide concentration as shown by a decrease in
      the relative stress from 0.98 to 0.53. The allyl sulfide-based thiol-yne
      methacrylate system exhibits stress relaxation up to 55% and increased T(g) up to
      40 degrees C compared with the control, AFCT-incapable thiol-yne. This ternary
      system has less than 1/3 of the stress of conventional dimethacrylate monomer
      resins while possessing similarly outstanding mechanical behavior.

PMID- 23162168
TI  - Schools, Their Spatial Distribution and Characteristics, and Fertility
      Limitation().
AB  - This paper investigates the complex relationship between various dimensions of
      women's educational context and their later life contraceptive use. Using data
      from rural Nepal on all the schools that ever existed in one community, I create
      geographically weighted measures of school characteristics-specifically teacher
      and student characteristics-that capture exposure to the complete array of
      schools and investigate the direct relationship between these dimensions of
      school characteristics and contraceptive use. These analyses provide new
      information on the broader issue of how social context influences the adoption of
      innovative behaviors by exploring the wide-reaching effects of school
      characteristics on individuals. Findings show that the gender of teachers and of
      other students, and the level of teacher education are all related to women's use
      of contraception; that increased exposure to these school characteristics
      throughout the study area, but not necessarily at the closest school, is related
      to higher rates of contraceptive use; and that school characteristics early in
      the life course can have long-term consequences for individual behavior.

PMID- 23162169
TI  - Phosphine Oxides as Stabilizing Ligands for the Palladium-Catalyzed Cross
      Coupling of Potassium Aryldimethylsilanolates.
AB  - The palladium-catalyzed cross-coupling reaction of potassium (4
      methoxyphenyl)dimethylsilanolate (K(+)1(-)) with aryl bromides has been
      demonstrated using triphenylphosphine oxide as a stabilizing ligand.
      Unsymmetrical biaryls can be prepared from a variety of aryl bromides in good
      yield with short reaction times. Qualitative kinetics studies compared effects of
      different phosphine oxides on the rate of cross-coupling and established the
      beneficial effect of these ligands in the reaction of electron-rich
      arylsilanolates. The improved yield and reproducibility of the cross-coupling of
      several bromides was demonstrated by direct comparison of reactions performed
      with and without triphenylphosphine oxide under non-rigorous exclusion of oxygen.

PMID- 23162170
TI  - Scaleable processes for the synthesis of (-)-beta-D-2,6-diaminopurine dioxolane
      (Amdoxovir, DAPD) and (-)-beta-D-2-aminopurine dioxolane (APD).
AB  - An efficient and scalable synthesis of (-)-DAPD and (-)-APD has been developed.
      We discovered that t-butyl cyanoacetate can be used as a new additive for the
      sugar nucleoside base coupling step en route to DAPD with improved beta
      selectivity and an isolated yield four fold greater than the original process
      scale method. Using this new process, (-)-DAPD has been prepared on greater than
      20 g scale. In the synthesis of (-)-APD, a key enzyme-catalyzed hydrolysis
      reaction afforded the water-soluble deprotected alpha-anomer while leaving the
      beta-anomer completely untouched.

PMID- 23162171
TI  - New methodology for the preparation of 3-hydroxy-2-pyridinone (3,2-HOPO)
      chelators and extractants. Part 2. Reactions of alcohols, phenols, and thiols
      with an electrophilic 3,2-HOPO reagent().
AB  - The reactions of the electrophilic iminium ester mesylate salt 1 with alcohols,
      phenols and thiols has been investigated. In the presence of base, thiols,
      phenols and thiophenol react with 1 to give the corresponding ether linked HOPO
      derivatives in good yields. However, the ring opening of salt 1 with alcohols
      could only be accomplished efficiently using a large excess of the alcohol in the
      presence of methanesulfonic acid at 80 degrees C. The synthetic utility of HOPO
      precursor, 1, has been demonstrated by the synthesis of two polyHOPO chelators 7
      and 9.

PMID- 23162172
TI  - Preparation of bifunctional isocyanate hydroxamate linkers: Synthesis of
      carbamate and urea tethered polyhydroxamic acid chelators.
AB  - Two novel bifunctional N-methylhydroxamate-isocyanate linkers 20 and 21 were
      prepared in good yield and high purity from the corresponding amine salts using a
      biphasic reaction with phosgene. The facile ring opening reaction of N-Boc
      lactams using the anion of O-benzylhydroxylamine gave the protected amino
      hydroxamates 6a and 6c in good yields. The selective methylation of the
      hydroxamate nitrogen in the presence of the N-Boc group in these intermediates
      could be readily accomplished. The utility of the linkers was clearly
      demonstrated by the synthesis of the carbamate-tethered trishydroxamic acid 27
      and the urea-tethered 29.

PMID- 23162173
TI  - Gender differences in scientific productivity: a persisting phenomenon?
AB  - There is substantial literature on research performance differences between male
      and female researchers, and its explanation. Using publication records of 852
      social scientists, we show that performance differences indeed exist. However,
      our case study suggests that in the younger generation of researchers these have
      disappeared. If performance differences exist at all in our case, young female
      researchers outperform young male researchers. The trend in developed societies,
      that women increasingly outperform men in all levels of education, is also
      becoming effective in the science system.

PMID- 23162174
TI  - On the relationship between citations of publication output and Hirsch index h of
      authors: conceptualization of tapered Hirsch index h(T), circular citation area
      radius R and citation acceleration a.
AB  - The nature of the empirical proportionality constant A in the relation L = Ah(2)
      between total number of citations L of the publication output of an author and
      his/her Hirsch index h is analyzed using data of the publication output and
      citations for six scientists elected to the membership of the Royal Society in
      2006 and 199 professors working in different institutions in Poland. The main
      problem with the h index of different authors calculated by using the above
      relation is that it underestimates the ranking of scientists publishing papers
      receiving very high citations and results in high values of A. It was found that
      the value of the Hirsch constant A for different scientists is associated with
      the discreteness of h and is related to the tapered Hirsch index h(T) by A(1/2) ~
      1.21h(T). To overcome the drawback of a wide range of A associated with the
      discreteness of h for different authors, a simple index, the radius R of circular
      citation area, defined as R = (L/pi)(1/2) ~ h, is suggested. This circular
      citation area radius R is easy to calculate and improves the ranking of
      scientists publishing high-impact papers. Finally, after introducing the concept
      of citation acceleration a = L/t(2) = pi(R/t)(2) (t is publication duration of a
      scientist), some general features of citations of publication output of Polish
      professors are described in terms of their citability. Analysis of the data of
      Polish professors in terms of citation acceleration a shows that: (1) the
      citability of the papers of a majority of physics and chemistry professors is
      much higher than that of technical sciences professors, and (2) increasing
      fraction of conference papers as well as non-English papers and engagement in
      administrative functions of professors result in decreasing citability of their
      overall publication output. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version
      of this article (doi:10.1007/s11192-012-0805-7) contains supplementary material,
      which is available to authorized users.

PMID- 23162175
TI  - Impact of ionizing radiation on physicochemical and biological properties of an
      amphiphilic macromolecule.
AB  - An amphiphilic macromolecule (AM) was exposed to ionizing radiation (both
      electron beam and gamma) at doses of 25 kGy and 50 kGy to study the impact of
      these sterilization methods on the physicochemical properties and bioactivity of
      the AM. Proton nuclear magnetic resonance and gel permeation chromatography were
      used to determine the chemical structure and molecular weight, respectively. Size
      and zeta potential of the micelles formed from AMs in aqueous media were
      evaluated by dynamic light scattering. Bioactivity of irradiated AMs was
      evaluated by measuring inhibition of oxidized low-density lipoprotein uptake in
      macrophages. From these studies, no significant changes in the physicochemical
      properties or bioactivity were observed after the irradiation, demonstrating that
      the AMs can withstand typical radiation doses used to sterilize materials.

PMID- 23162176
TI  - A Contextual Comparison of Risk Behaviors Among Older Adult Drug Users and Harm
      Reduction in Suburban Versus Inner-City Social Environments.
AB  - Recent epidemiological data show that older adults comprise a growing age group
      of drug users and new AIDS cases in the United States. Prevention and
      intervention studies show that risk behaviors leading to HIV infection are
      increasing among older users, particularly among the socially vulnerable. Yet
      older adults remain an under-researched population of drug users and little is
      known about their risk behaviors. Our aim is to address this gap in knowledge on
      older users by comparing contextual factors that influence risk behaviors and
      harm reduction strategies practiced by older drug users living in different
      communities. This study is based on ethnographic fieldwork in suburban and inner
      city neighborhoods in a large metropolitan area in the southeastern USA.
      Interviewers conducted face-to-face, in-depth, life-history interviews with 69
      older adults (age 45 and older) who used heroin, cocaine, and/or methamphetamine.
      Findings show that while risk behaviors were similar among older adult drug users
      living in suburban and inner-city environments, the provision of harm reduction
      education and paraphernalia varied widely. The results show the need for the
      expansion of harm reduction services focused on older adult drug users who are
      homeless, uninsured, or socially isolated. This application-oriented research
      will inform healthcare and treatment providers and generate new directions for
      future collaborative harm reduction services aimed to decrease the spread of HIV
      and other infectious diseases associated with drug use.

PMID- 23162178
TI  - Measurement of stainer bath contamination and evaluation of common mitigation
      strategies.
AB  - Methods relative to the staining of tissues using hematoxylin and eosin (H&E)
      have largely not evolved beyond linear batch staining processes. The batching of
      slides in the histopathology laboratory inherently leads to the sharing of the
      various reagents among those specimens being processed through the baths. Studies
      analyzing the effects of reagent sharing during the common H&E linear staining
      method are limited. This study assessed rates of extraneous tissue contamination
      found in selected stainer bath containers from the deparaffinization portion of
      the H&E linear staining procedure. The impact of common mitigation strategies on
      those rates of contamination was evaluated.

PMID- 23162177
TI  - Cognitive and Interpersonal Moderators of Daily Co-Occurrence of Anxious and
      Depressed Moods in Generalized Anxiety Disorder.
AB  - Anxiety and depression co-occur, both at the disorder and symptom levels, and
      within anxiety disorders, fluctuations in daily anxious mood correspond
      temporally to fluctuations in depressed mood. However, little is known about the
      factors or conditions under which anxiety and depressive symptoms are most likely
      to co-occur. The current study investigated the role of cognitive factors (daily
      rumination and cognitive attributions about anxiety symptoms) and interpersonal
      functioning (daily perceived rejection, support, criticism, and interpersonal
      problems) as moderators of the daily association between anxious and depressed
      moods. Fifty-five individuals with generalized anxiety disorder completed a 21
      day diary assessing daily mood and cognitive and interpersonal functioning.
      Ratings of anxious and depressed mood were more closely associated on days when
      participants ruminated about their anxiety or viewed anxiety symptoms more
      negatively. Furthermore, anxious mood predicted later depressed mood on days when
      participants reported greater interpersonal problems and more perceived
      rejection. Results suggest that cognitive and interpersonal factors may elevate
      the likelihood of anxiety-depression co-occurrence.

PMID- 23162179
TI  - Information Processing from Infancy to 11 Years: Continuities and Prediction of
      IQ.
AB  - This study provides the first direct evidence of cognitive continuity for
      multiple specific information processing abilities from infancy and toddlerhood
      to pre-adolescence, and provides support for the view that infant abilities and
      form the basis of later childhood abilities. Data from a large sample of children
      (N = 131) were obtained at five different time points (7, 12, 24, 36 months, and
      11 years) for a large battery of tasks representing four cognitive domains
      (attention, processing speed, memory, and representational competence).
      Structural equation models of continuity were assessed for each domain, in which
      it was assumed that infant abilities -> toddler abilities -> 11-year abilities.
      Abilities at each age were represented by latent variables, which minimize task
      specific variance and measurement error. The model for each domain fit the data.
      Moreover, abilities from the three age periods predicted global outcome, with
      infant, toddler, and contemporaneous 11-year measures, respectively, accounting
      for 12.3%, 18.5%, and 45.2% of the variance in 11-year IQ. These findings
      strengthen contentions that specific cognitive abilities that can be identified
      in infancy show long-term continuity and contribute importantly to later
      cognitive competence.

PMID- 23162180
TI  - European Regional Populations: Current Trends, Future Pathways, and Policy
      Options.
AB  - Europe is currently experiencing an ageing population and slowing population
      growth of both the total and working-age populations. These trends are likely to
      continue. Even though population ageing will affect all European regions,
      different regions will be affected in different ways. Even under favorable
      conditions, 35-40 % of all NUTS2 regions will face a labor force decline. If
      economic conditions are poor, some regions may continue to grow, but 55-70 % of
      the regions will see a labor force decline by 10 % or more. In most regions of
      Eastern Europe, the labor force may decrease by more than 30 %. To keep regions
      prosperous (maintaining competitiveness) and to avoid worse inequality
      (maintaining cohesion), policy-makers must find ways to cope with these
      challenges through new fiscal and social policies, though policies directly
      affecting demographic and migratory trends may also be needed.

PMID- 23162181
TI  - Particle systems for adaptive, isotropic meshing of CAD models.
AB  - We present a particle-based approach for generating adaptive triangular surface
      and tetrahedral volume meshes from computer-aided design models. Input shapes are
      treated as a collection of smooth, parametric surface patches that can meet non
      smoothly on boundaries. Our approach uses a hierarchical sampling scheme that
      places particles on features in order of increasing dimensionality. These
      particles reach a good distribution by minimizing an energy computed in 3D world
      space, with movements occurring in the parametric space of each surface patch.
      Rather than using a pre-computed measure of feature size, our system
      automatically adapts to both curvature as well as a notion of topological
      separation. It also enforces a measure of smoothness on these constraints to
      construct a sizing field that acts as a proxy to piecewise-smooth feature size.
      We evaluate our technique with comparisons against other popular triangular
      meshing techniques for this domain.

PMID- 23162182
TI  - Individual and Social Network Sexual Behavior Norms of Homeless Youth at High
      Risk for HIV Infection.
AB  - Although previous research shows that homeless youth engage in numerous risky
      sexual behaviors, little is known about whether or not specific rules govern this
      conduct within their social networks and how group norms influence subsequent
      sexual actions. The current study utilizes 19 in-depth interviews with homeless
      youth to investigate different elements of their sexual behavior. Findings reveal
      that their decision to have sex generally depends on chemistry and physical
      appearance whereas a potential partner's risky sexual history and heavy substance
      use discourages youth from engaging in sex. Both males and females discuss condom
      usage as it relates to unknown sexual history, availability, pregnancy, and the
      prevention of sexually transmitted infections (STIs). Sixteen homeless youth
      indicate that they do not discuss safe sex practices with their partners or
      social network members.

PMID- 23162183
TI  - Non-compliance in pharmacotherapy.

PMID- 23162184
TI  - Metabolic syndrome in bipolar disorders.
AB  - To review the data with respect to prevalence and risk factors of metabolic
      syndrome (MetS) in bipolar disorder patients. Electronic searches were done in
      PUBMED, Google Scholar and Science direct. From 2004 to June 2011, 34 articles
      were found which reported on the prevalence of MetS. The sample size of these
      studies varied from 15 to 822 patients, and the rates of MetS vary widely from
      16.7% to 67% across different studies. None of the sociodemographic variable has
      emerged as a consistent risk factor for MetS. Among the clinical variables longer
      duration of illness, bipolar disorder- I, with greater number of lifetime
      depressive and manic episodes, and with more severe and difficult-to-treat index
      affective episode, with depression at onset and during acute episodes, lower in
      severity of mania during the index episode, later age of onset at first manic
      episode, later age at first treatment for the first treatment for both phases,
      less healthy diet as rated by patients themselves, absence of physical activity
      and family history of diabetes mellitus have been reported as clinical risk
      factors of MetS. Data suggests that metabolic syndrome is fairly prevalent in
      bipolar disorder patients.

PMID- 23162185
TI  - The effect of anxiety on breast cancer patients.
AB  - Cancer is a disease wherein abnormal cells divide without control and are able to
      attack other tissues. Most of the patients and their families face some degree of
      depression, anxiety, and fear when cancer becomes a part of their lives. They
      feel helpless and eager to find ways on how to get rid of it. The study focuses
      on anxiety among breast cancer patients. It aims at investigating cancer, its
      symptoms, and effects the disease has on the anxiety level of patients.

PMID- 23162186
TI  - Evaluation of antidepressant and anxiolytic activity of phosphodiesterase 3
      inhibitor - cilostazol.
AB  - BACKGROUND: Cyclic nucleotide Phosphodiesterases (PDEs) are ubiquitously
      distributed in mammalian tissues and play a major role in cell signaling by
      hydrolyzing cyclic Adenosine Monophosphate (cAMP) and cyclic Guanosine
      Monophosphate (cGMP). Impairments in signal transduction have been implicated as
      possible mechanism of reduced plasticity and neuronal survival in major
      depressive disorders. PDE inhibitors possess a potentially powerful means to
      manipulate secondary messengers involved in learning, memory and mood. Cilostazol
      is an antiplatelet agent indicated for the treatment of intermittent claudication
      with peripheral artery occlusion and for the prevention of ischemic stroke
      worldwide. Various animal studies have reported neuroprotective, anti apoptotic,
      cognition and cerebral blood flow improvement properties of cilostazol. MATERIALS
      AND METHODS: In this study, the antidepressant and anxiolytic effects of
      cilostazol were evaluated in mice using behavioral tests sensitive to clinically
      effective antidepressant compound. RESULTS: Cilostazol, administered
      intraperitoneally (20 mg/kg), decreased immobility time of mice when subjected to
      forced swim test and tail suspension test as compared to standard fluoxetine (20
      mg/kg). Cilostazol also produced significant decrease in the number of marbles
      buried as compared to fluoxetine in marble burying model. CONCLUSION: The present
      study suggests that cilostazol possesses potential antidepressant and anxiolytic
      activity, which could be of therapeutic interest for use in patients with
      depressive disorders.

PMID- 23162187
TI  - Psychomotor performance of medical students: effect of 24 hours of sleep
      deprivation.
AB  - CONTEXT: Sleep deprivation is known to have detrimental effects on attentional
      resources and cognitive functions. AIM: The aim of this study is to assess the
      changes in performance, due to 24 h of sleep deprivation, in medical students
      MATERIALS AND METHODS: The performance was assessed using simple paper-pencil
      tasks, such as digit symbol substitution test, digit vigilance test, and letter
      cancellation tasks. RESULTS: The results revealed an increase in the number of
      errors in letter cancellation tasks and digit vigilance test, with a significant
      decrease in the number of correct responses on the letter cancellation task. The
      time taken to complete the tests increased with lack of sleep, with the digit
      symbol substitution test being affected the most. DISCUSSION: This study infers
      that sleep deprivation for 24 h affected the judgment ability more than the
      response speed. CONCLUSION: Sleep deprivation might lead to compromised
      performance of medical students in examinations.

PMID- 23162188
TI  - Volume and asymmetry abnormalities of insula in antipsychotic-naive
      schizophrenia: a 3-tesla magnetic resonance imaging study.
AB  - CONTEXT: Insula, which is a vital brain region for self-awareness, empathy, and
      sensory stimuli processing, is critically implicated in schizophrenia
      pathogenesis. Existing studies on insula volume abnormalities report inconsistent
      findings potentially due to the evaluation of 'antipsychotic-treated'
      schizophrenia patients as well as suboptimal methodology. AIM: To understand the
      role of insula in schizophrenia. MATERIALS AND METHODS: In this first-time 3-T
      magnetic resonance imaging study, we examined antipsychotic-naive schizophrenic
      patients (N=30) and age-, sex-, handedness- and education-matched healthy
      controls (N=28). Positive and negative symptoms were scored with good interrater
      reliability (intraclass correlation coefficient (ICC)>0.9) by using the scales
      for negative and positive symptoms. Gray matter volume of insula and its
      anterior/posterior subregions were measured by using a three-dimensional,
      interactive, semiautomated software based on the valid method with good
      interrater reliability (ICC>0.85). Intracranial volume was automatically measured
      by using the FreeSurfer software. RESULTS: Patients had significantly deficient
      gray matter volumes of left (F=33.4; P<0.00001) and right (F=11.9; P=0.001)
      insula after controlling for the effects of age, sex, and intracranial volume.
      Patients with predominantly negative symptoms had a significantly deficient right
      posterior insula volume than those with predominantly positive symptoms (F=6.3;
      P=0.02). Asymmetry index analysis revealed anterior insular asymmetry to be
      significantly reversed (right>left) in male patients in comparison with male
      controls (left>right) (t=2.7; P=0.01). CONCLUSIONS: Robust insular volume
      deficits in antipsychotic-naive schizophrenia support intrinsic role for insula
      in pathogenesis of this disorder. The first-time demonstration of a relationship
      between right posterior insular deficit and negative symptoms is in tune with the
      background neurobiological literature. Another novel observation of sex-specific
      anterior insular asymmetry reversal in patients supports evolutionary postulates
      of schizophrenia pathogenesis.

PMID- 23162189
TI  - Effect of a single dose of dextromethorphan on psychomotor performance and
      working memory capacity.
AB  - BACKGROUND: Previous studies show that the prolonged use of dextromethorphan
      produces cognitive deterioration in humans. AIM: The aim of this study was to
      investigate the effect of a single dose of dextroemthrophan on psychomotor
      performance and working memory capacity. MATERIALS AND METHODS: This is a
      randomized, double-blind, controlled, and prospective study. Thirty-six (17
      women, 19 men) medical students enrolled in the study; half of them (7 women, 11
      men) were given placebo, while the other half (10 women, 8 men) received
      dextromethorphan. The choice reaction time, critical flicker fusion threshold,
      and N-back working memory task were measured before and after 2 h of taking the
      drugs. RESULTS: Dextromethorphan showed a significant deterioration in the 3-back
      working memory task (P<0.05). No significant changes were seen as regards the
      choice reaction time components (total, recognition, motor) and critical flicker
      fusion threshold (P>0.05). On the other hand, placebo showed no significant
      changes as regards the choice reaction time, critical flicker fusion threshold,
      and N-back working memory task (P>0.05). CONCLUSION: A single dose of
      dextromethorphan has no effect on attention and arousal but may significantly
      impair the working memory capacity.

PMID- 23162190
TI  - Evaluation of psychological aspects among subtypes of irritable bowel syndrome.
AB  - CONTEXT: While some studies have found disparities between subtypes of irritable
      bowel syndrome (IBS), others did not found such differences. AIM: This study
      aimed to investigate whether there are differences in psychological features
      between the subtypes of IBS. SETTINGS AND DESIGN: A cross-sectional study was
      performed on all consecutive outpatients IBS diagnosed (from Oct. 2010 to Oct.
      2011) in Taleghani Hospital gastroenterology clinic, Tehran, Iran. MATERIALS AND
      METHODS: A total of 153 consecutively diagnosed IBS patients (using Rome III
      criteria); including 80 constipation-predominant (IBS-C), 22 diarrhea-predominant
      (IBS-D), and 51 mixed IBS (IBS-M) were asked to complete the Symptom Checklist 90
      Revised (SCL-90-R). STATISTICAL ANALYSIS: Pearson's chi-square test was used to
      compare nominal variables. One-way ANOVA was used to compare continuous
      variables. RESULTS: Although IBS-C patients were more suffered from psychiatric
      disorders, there were no statistical differences between mean score of IBS-C, IBS
      D, and IBS-M patients regarding to all of SCL-90-R subscales and three global
      indices including Global Severity Index (GSI), Positive Symptom Distress Index
      (PSDI) and Positive Symptom Total (PST) (P<0.05). CONCLUSION: Our finding showed
      that there are no different symptomatic profiles between IBS subtypes.

PMID- 23162191
TI  - The Process and Challenges in the Translation of World Health Organization
      Quality of Life (WHOQOL- BREF) to a Regional Language; Malayalam.
AB  - A lot of research has been directed on wellbeing and disability in many non
      communicable disease conditions. In this context, health-related aspects of life
      and quality of life (QOL) are receiving a lot of focus. Many Quality of Health
      measures are available, of which World Health Organization Quality of Life
      (WHOQOL-BREF) is one of the most popular. Translating and adapting this tool is
      useful in view of research happening in a multicultural arena. Though
      translations into Hindi and other Indian languages including Tamil and Kannada
      have been done, a Malayalam version is not available. This paper discusses the
      steps adopted in this exercise and the challenges in translating WHOQOL-BREF to
      Malayalam from the original English version.

PMID- 23162192
TI  - Reasons for help-seeking and associated fears in subjects with substance
      dependence.
AB  - BACKGROUND: Patients seek treatment for substance use disorders because of
      certain reasons that they consider significant and important, but on the other
      hand, they do have various fears or apprehensions about the treatment, which act
      as barriers for treatment-seeking. In this study, we aim to assess their reasons
      for seeking treatment, the associated fears about treatment, their social support
      and locus of control, and also to find the relationship among these variables.
      MATERIALS AND METHODS: One hundred subjects attending the Drug Deaddiction and
      Treatment Center, Postgraduate Institute of Medical Education and Research
      (PGIMER) were prospectively recruited, with purposive sampling from 15 June to 14
      July, 2011. The sociodemographic and clinical variables were ascertained through
      a semi-structured performa. The PGI Locus of Control Scale, Social Support Scale,
      and Reasons of Help-seeking and Fear Questionnaire were applied. RESULTS: The
      common reasons for seeking treatment were - having become a habitual user, taking
      substance for a long time, and a need to take it every day. The common fears
      about treatment were the fear of disappointing others, loss of secrecy of
      substance use, and being considered a failure in life. The locus of control was
      primarily internal. Certain reasons like taking substance for a long time,
      feeling ill, and feeling sad were associated with a lower social support. Social
      support was not associated with the locus of control. The most affected areas of
      impairment were finance and health. CONCLUSIONS: Certain reasons and fears
      regarding treatment are more common than others. It is important to look into
      reasons and fears that are related to better treatment outcomes.

PMID- 23162193
TI  - Psychosocioeconomic study of medically unexplained physical symptoms.
AB  - BACKGROUND: There is a paucity of studies done on medically unexplained physical
      symptoms (MUPS) in Kerala, India. The objective of this study was to examine the
      sociodemographic and other clinical variables associated with this condition.
      MATERIALS AND METHODS: The clinical sample was taken from the General Medicine
      Clinic of a tertiary care hospital, in Kerala. The referred cases meeting the
      criteria (N=48) for medically unexplained physical symptoms were enrolled for
      this cross-sectional study. The medical doctor with experience in psychiatry
      completed the questionnaire. RESULTS: Most of the patients were middle-aged
      females from rural areas. The most common symptom reported was headache. Most of
      the patients had symptoms for five years or more and had seen two-to-five
      consultants. A majority of the patients had undergone special investigations and
      a few had expensive and invasive investigations. Cluster C personality disorders
      were the most common associated personality disorders with medically unexplained
      physical symptoms. CONCLUSIONS: To our knowledge this is the first
      psychosocioeconomic study on medically unexplained physical symptoms, done in
      Kerala, India. Medically unexplained physical symptoms cause loss of productivity
      and economic burden and are a major public health problem. Future studies are
      warranted focusing on non-pharmacological treatment, psycho-education on mind
      body association, and medical models on specific cytokines associated with
      medically unexplained physical symptoms for personalized management, and to
      examine the effect of a combination of pharmacotherapy and cognitive behavioral
      therapy.

PMID- 23162194
TI  - Entorhinal Cortex Volume in Antipsychotic-naive Schizophrenia.
AB  - BACKGROUND: Entorhinal cortex (ERC), a multimodal sensory relay station for the
      hippocampus, is critically involved in learning, emotion, and novelty detection.
      One of the pathogenetic mechanistic bases in schizophrenia is proposed to involve
      aberrant information processing in the ERC. Several studies have looked at
      cytoarchitectural and morphometric changes in the ERC, but results have been
      inconsistent possibly due to the potential confounding effects of antipsychotic
      treatment. MATERIALS AND METHODS: In this study, we have examined the entorhinal
      cortex volume in antipsychotic-naive schizophrenia patients (n=40; M:F=22:18) in
      comparison with age, sex, and handedness, matched (as a group) with healthy
      subjects (n=42; M:F=25:17) using a valid method. 3-Tesla MR images with 1-mm
      sections were used and the data was analyzed using the SPSS software. RESULTS:
      Female schizophrenia patients (1.25+/-0.22 mL) showed significant volume deficit
      in the right ERC in comparison with female healthy controls (1.45+/-0.34 mL)
      (F=4.9; P=0.03), after controlling for the potential confounding effects of
      intracranial volume. However, male patients did not differ from male controls.
      The left ERC volume did not differ between patients and controls. CONCLUSIONS:
      Consistent with the findings of a few earlier studies we found a reduction in the
      right ERC volume in patients. However, this was limited to women. Contextually,
      our study finding supports the role for ERC deficit in schizophrenia pathogenesis
      - perhaps mediated through aberrant novelty detection. Sex-differential
      observation of ERC volume deficit in schizophrenia needs further studies.

PMID- 23162195
TI  - Rapid response with ketamine on suicidal cognition in resistant depression.
AB  - CONTEXT: Suicidal ideation in depressed patients is a serious and emergent
      condition that requires urgent intervention. Intravenous ketamine, an N-methyl-D
      aspartate (NMDA) antagonist, has shown rapid antidepressant effects, making it a
      potentially attractive candidate for depressed patients with suicidal risk. AIMS:
      In India few studies have corroborated such findings; the present study aimed to
      assess the effectiveness and sustainability of antisuicidal effects of ketamine
      in subjects with resistant depression. SETTINGS AND DESIGN: Single-center,
      prospective, 4 weeks, open-label, single-arm pilot study. MATERIALS AND METHODS:
      Twenty-seven subjects with DSM-IV major depression (treatment resistant) were
      recruited. The subjects were assessed on Scale for Suicidal Ideation (SSI), 17
      item Hamilton Depression Rating Scale (HDRS). After a 2-week drug-free period,
      subjects were given a single intravenous infusion of ketamine hydrochloride (0.5
      mg/kg) and were rated at baseline and at 40, 80, 120, and 230 minutes and 1 and 2
      days postinfusion. RESULTS: The ketamine infusion was effective in reducing the
      SSI and HDRS scores, the change remained significant from minute 40 to 230 at
      each time point. CONCLUSIONS: The real strength of this study rests in
      documenting the rapid albeit short-lasting effect of ketamine on suicidal
      ideation in depressed patients.

PMID- 23162196
TI  - Short-term diagnostic stability of acute psychosis: data from a tertiary care
      psychiatric center in South India.
AB  - CONTEXT: Studies on acute psychosis in patients from India report good outcome. A
      small proportion of these patients may suffer relapses or other develop major
      psychiatric disorders later. AIM: The aim of this study was to examine the
      diagnostic stability of acute psychosis in patients from India. MATERIALS AND
      METHODS: The records of patients who presented with the first episode of acute
      and transient psychotic disorder (n=57) over 1 year (2004) were analyzed, and the
      follow-up data at the end of 1 and 2 years were recorded. RESULTS: The mean age
      of the sample was 30.72 years. The mean duration of illness episode was 18.15+/
      17.10 days. The follow-up data were available for 77.2% (n=44) and 75.4% (n=43)
      of the sample at the end of first and second years. Relapse was recorded in 47.4
      and 54.4% at the end of first and second years, respectively. CONCLUSION: The
      diagnosis changed into other disorders such as bipolar disorder, schizophrenia,
      and unspecified psychosis, while a majority retained the initial diagnosis of
      acute psychosis. The findings suggest that acute psychosis is a relatively stable
      condition. A small percentage of these patients may go on to develop
      schizophrenia or bipolar disorder.

PMID- 23162197
TI  - Obsessive compulsive disorder masquerading as psychosis.
AB  - Obsessive compulsive disorder (OCD) is commonly regarded as a disorder with good
      insight. However, it has now been recognized that insight varies in these
      patients. Pathological beliefs seem to lie on a continuum of insight, with full
      insight at one end and delusion at the other. This can indeed pose a considerable
      challenge, especially in a scenario where the phenomenon is difficult to discern.
      We report a case of OCD, which was initially diagnosed as psychosis.

PMID- 23162198
TI  - Chronic subdural hematoma following electro convulsive therapy.
AB  - Subdural hematoma is a rare but serious complication following electroconvulsive
      therapy (ECT), a frequently used treatment modality in the management of various
      psychiatric morbidities including bipolar affective disorder (BAD). There are
      very few reports of intracranial bleeding following ECT in the literature. A 38
      year-old female, known case of BAD for last fifteen years receiving ECT,
      presented with the symptoms of dysphasia, headache, left sided paresis, and
      sudden deterioration of sensorium. Computed tomography (CT) scan of the brain was
      suggestive of left-sided fronto parietal chronic subdural hematoma with midline
      shift that was drained successfully.

PMID- 23162199
TI  - Rubinstein-taybi syndrome with psychosis.
AB  - Rubinstein-Taybi syndrome (RTS) is a rare genetic disorder with characteristic
      physical anomalies. It is characterized by mental retardation, postnatal growth
      deficiency, microcephaly, specific facial characteristics, broad thumbs, and big
      toes. Behavioral problems are common with RTS; they include mental retardation,
      impulsivity, distractibility, instability of mood, stereotypes, poor
      coordination, atypical depression, and mania. To date, there is lack of
      literature on the presence of schizophrenia or non-affective psychosis with RTS.
      Here, we describe two cases where there is co-morbid psychosis with RTS. One case
      is diagnosed as paranoid schizophrenia and the other as psychosis possibly
      schizophrenia. Genetic analysis was not done due to unavailability. The possible
      etiological factors for the association of psychosis with RTS are discussed.
      Factors such as regulators of RNA polymerase II and hypoxia-inducible factor 1
      alpha (HIF1A) may be some common etiological factors for the association of
      schizophrenia or non-affective psychosis and RTS. Schizophrenia / non-affective
      psychosis can be a comorbid psychiatric condition with RTS.

PMID- 23162200
TI  - Tardive dystonia with olanzapine: a rare case report.
AB  - Olanzapine is an atypical antipsychotic drug which is available in oral and
      injectable forms that is used for treatment of various psychiatric disorders. We
      report a rare case of tardive dystonia after receiving single dose of olanzapine
      (10 mg) in parental form. Clinicians should be very vigilant regarding this rare
      side effect with use of olanzapine in clinical practice.

PMID- 23162201
TI  - Social dichotomy versus gender dichotomy: a case report of gender identity
      disorder.
AB  - Gender identity disorder is one of the most controversial diagnoses of DSM-IV and
      almost incomparable in the complexity of its social, ethical and political
      considerations to any other diagnosis. We present a case of 30 year-old male who
      presented with complaints of suggestive of depressive disorder with a recent
      suicidal attempt. Careful history taking reveals underlying conflicts with
      prominent gender dysphoria and social complexities. The patient is managed
      primarily by pharmacotherapy and harm reduction model. Our case reflects a unique
      coping strategy against the present sociocultural values and ambiguity of law in
      this part of the world.

PMID- 23162202
TI  - Phobias in Poetry: Coleridge's Ancient Mariner.
AB  - The Rime of the Ancient Mariner was written by Coleridge and is a classic poetry
      about retribution, punishment, guilt, and curse. Religious beliefs and delusions
      can arise from neurologic lesions and anomalous experiences, suggesting that at
      least some religious beliefs can be pathological. Looking at the poem through the
      psychiatric and psychological domain, the symbolism, the narration and the entire
      setting of the poem represents Post Traumatic Stress Disorder. Mariner's
      reactions are beautifully portrayed from the psychoanalytic point of view and the
      literary piece shows claustrophobia, stygiophobia, dikephobia, and poinephobia.
      The mental stress of a person under a crisis situation has remarkably been evoked
      in this poem. This incredible piece of art expresses how the realization of
      divine love within oneself has the power to heal pain and suffer.

PMID- 23162203
TI  - Indianizing psychiatry - has the case been made enough?

PMID- 23162204
TI  - Disability and psychiatric disorders.

PMID- 23162205
TI  - Don't get the blues: conspicuous nuptial colouration of male moor frogs (Rana
      arvalis) supports visual mate recognition during scramble competition in large
      breeding aggregations.
AB  - Conspicuous male colouration is expected to have evolved primarily through
      selection by female choice. In what way conspicuous colours could be advantageous
      to males scrambling for mates remains largely unknown. The moor frog (Rana
      arvalis) belongs to the so-called explosive breeders in which spawning period is
      short; intrasexual competition is strong, and males actively search and scramble
      for females. During breeding, male body colouration changes from a dull brown
      (similar to females) to a conspicuous blue, and we wanted to test if male
      blueness influences mating success or facilitates male mate recognition. To do
      so, we first measured the colour of mated and non-mated males using a
      spectrophotometer. In an experiment, we then analysed interactions of actual male
      moor frogs in natural spawning aggregations with a brown (resembling a female or
      a non-breeding male) and a blue model frog. Mated and non-mated males did not
      differ in colouration, suggesting that female choice based on colour traits was
      unlikely. In our behavioural experiment, male moor frogs spent significantly more
      time in contact and in amplexus with the brown model than with the blue model.
      Our results suggest that the nuptial colouration in moor frogs can act as a new
      type of visual signal in anurans evolved to promote instantaneous mate
      recognition allowing males to quickly move between rivals while scrambling for
      females. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article
      (doi:10.1007/s00265-012-1412-6) contains supplementary material, which is
      available to authorized users.

PMID- 23162206
TI  - Does mating experience of male house crickets affect their behavior to subsequent
      females and female choice?
AB  - Male mating experience was shown to play an important role in settling conflicts
      between males; however, little is known about whether and how prior access to
      females influences male behavior during intersexual interactions and female
      choice itself. Here, I experimentally test this relationship in the house cricket
      (Acheta domesticus) by combining one-on-one interaction between the male and
      female with direct comparison of males by the female, but precluding aggression
      between males. I found that solitary males were more active during subsequent
      courtship displays than paired males, suggesting the detrimental effect of mating
      on courtship performance. At the same time, females spent significantly more time
      close to solitary males or playbacks of male's natural courtship songs, and
      responded positively to the condition of males, ignoring body size of males. In
      contrast, females responded similarly to computer-modified playbacks of courtship
      songs of solitary and paired males with standardized rate of phrases and
      amplitudes; however, when females were additionally allowed to contact with
      anesthetized males they spent more time close to bigger males, irrespective of
      the acoustic parameters of courtship songs. These results show that although
      females were able to differentiate between many behavioral and morphological
      characteristics of males, including voluntary and intrinsic ones, they preferred
      traits conditional upon the costliness of male's displays. In addition, mating
      experience appeared to be a crucial factor in the choice of a particular costly
      mating strategy by males.

PMID- 23162207
TI  - (111)In- and (203)Pb-Labeled Cyclic RGD Peptide Conjugate as an alpha(v)beta(3)
      Integrin-Binding Radiotracer.
AB  - Methodology for site-specific modification and chelate conjugation of a cyclic
      RGD (cRGD) peptide for the preparation of a radiotracer molecular imaging agent
      suitable for detecting alpha(v)beta(3) integrin is described. The method involves
      functionalizing the peptide with an aldehyde moiety and conjugation to a 1,4,7,10
      tetraazacyclododecane-N,N',N",N'''-tetraacetic acid (DOTA) derivative that
      possesses an aldehyde reactive aminooxy group. The binding assay of the (111)In
      labeled peptide conjugate with alpha(v)beta(3) integrin showed 60% bound when
      four equivalents of the integrin was added, a reasonable binding affinity for a
      mono-valent modified RGD peptide.

PMID- 23162208
TI  - Youth Psychopathic Traits Inventory-Short Version: A Further Test of the Internal
      Consistency and Criterion Validity.
AB  - The Youth Psychopathic Traits Inventory-Short Version (YPI-S; van Baardewijk et
      al., 2010) is a self-report measure to assess psychopathic-like traits in
      adolescents. The aim of the present study is to investigate the factor structure,
      the internal consistency, and the criterion validity of the YPI-S in 768 Belgian
      community adolescents (45.4 % males). In general, our study supported the YPI
      three factor structure while relevant indices showed that the instrument is
      internally consistent. In addition, relations between the YPI-S total score and
      dimension scores on the one hand and external criterion measures (e.g. conduct
      problems and self-reported offending) on the other hand were generally in line
      with predictions. The present study replicated and substantially extended
      previous findings of the YPI-S in a sample of community youth. Future studies are
      needed to test whether findings from community samples can be replicated in
      clinical-referred and justice-involved boys and adolescents.

PMID- 23162209
TI  - Synthesis and Characterization of Thiol-Ene Functionalized Siloxanes and
      Evaluation of their Crosslinked Network Properties.
AB  - Three types of linear thiol-functionalized siloxane oligomers and three types of
      ene-functionalized oligomers were synthesized and subsequently photopolymerized.
      Within each type of thiol-functionalized oligomer, the ratio of mercaptan repeat
      units to non-reactive phenyl repeat units was varied to manipulate both the
      crosslink density and the degree of secondary interactions through pi-pi
      stacking. Similarly, the repeat units of the three ene-functionalized oligomers
      are composed of allyl-functional monomers, benzene-functional monomers, and octyl
      functional monomers in varying ratios of benzene:octyl but with a constant
      fraction of allyl moieties. The structural composition of the siloxane oligomers
      plays a pivotal role in the observed material properties of networks formed
      through thiol-ene photopolymerization. Networks with a high concentration of
      thiol functionalities exhibit higher rubbery moduli, ultimate strengths, and
      Young's moduli than networks with lower thiol concentrations. Moreover, the
      concentration of functionalities capable of participating in secondary
      interactions via hydrogen bonding or pi-pi stacking directly impacts the network
      glass transition temperature and elasticity. The combination of low crosslink
      density and high secondary interactions produces networks with the greatest
      toughness. Finally, the fraction of octyl repeats correlates with the hydrophobic
      nature of the network.

PMID- 23162210
TI  - An Examination of Early Maladaptive Schemas among Substance Use Treatment Seekers
      and their Parents.
AB  - Early maladaptive schemas, which are cognitive and behavioral patterns of viewing
      oneself and the world that result in substantial distress, are gradually being
      documented as important vulnerabilities for substance abuse. Unfortunately, there
      is limited research on early maladaptive schemas among substance abusers and
      their family members. Research on this topic may carry important implications for
      family-focused substance use interventions. The current study examined
      similarities and differences in early maladaptive schemas among a sample of
      substance abuse treatment seeking adults (n = 47) and at least one parent (n =
      58). Results demonstrated that the substance abusers scored higher than their
      parents on 17 of 18 early maladaptive schemas, with most differences falling into
      the large effect size range. There were some similarities in the specific early
      maladaptive schemas endorsed by both groups despite substance abusers scoring
      higher on all schemas. Implications of these findings for future research and
      family-focused substance use treatment programs are discussed.

PMID- 23162211
TI  - SOCIAL DISCOUNTING AND CIGARETTE SMOKING DURING PREGNANCY.
AB  - In this study we examined the association between social discounting and smoking
      status in a cohort of pregnant cigarette smokers (n=91), quitters (n=27), or
      never-smokers (n=30). The smokers and quitters were participants in clinical
      trials on smoking cessation and relapse prevention, while the never-smokers were
      controls in a study on nicotine withdrawal during pregnancy. Social discounting
      was assessed using a paper and pencil task that assesses the amount of
      hypothetical money a person is willing to forgo in order to share with
      individuals in their social network ranging from the person who is emotionally
      closest to them to a mere acquaintance. The amount that women were willing to
      forgo in order to share decreased hyperbolically as a function of social
      distance, with smokers exhibiting steeper discounting functions (i.e., less
      generosity) than quitters or never-smokers; discounting functions of quitters and
      never-smokers did not differ significantly. In multivariate analyses controlling
      for potential sociodemographic and other confounds, social discounting remained a
      significant predictor of smoking status among smokers versus quitters. Overall,
      these results suggest that individual differences in social discounting may be a
      factor influencing the choices that women make about quitting smoking upon
      learning of a pregnancy.

PMID- 23162212
TI  - Wound healing through the ages.

PMID- 23162213
TI  - Patient education is equally important.

PMID- 23162214
TI  - Lt. General N. C. Sanyal (PVSM; PHS).

PMID- 23162215
TI  - Advanced skin, scar and wound care centre for children: A new era of care.
AB  - Advanced wound care centres are now a well established response to the growing
      epidemic of chronic wounds in the adult population. Is the concept transferable
      to children? Whilst there is not the same prevalence of chronic wounds in
      children there are conditions affecting the integumentary system that do have a
      profound effect on the quality of life of both children and their families. We
      have identified conditions involving the skin, scars and wounds which contribute
      to a critical number of potential patients that can justify the setting up of an
      advanced skin, scar and wound care centre for children. The management of
      conditions such as giant naevi, extensive scarring and epidermolysis bullosa
      challenge medical professionals and lead to new and novel treatments to be
      developed. The variation between and within such conditions calls for a
      customizing of individual patient care that involves a close relationship between
      research scientists and clinicians. This is translational medicine of its best
      and we predict that this is the future of wound care particularly and
      specifically in children.

PMID- 23162216
TI  - Wound bed preparation from a clinical perspective.
AB  - Wound bed preparation has been performed for over two decades, and the concept is
      well accepted. The 'TIME' acronym, consisting of tissue debridement, infection or
      inflammation, moisture balance and edge effect, has assisted clinicians
      systematically in wound assessment and management. While the focus has usually
      been concentrated around the wound, the evolving concept of wound bed preparation
      promotes the treatment of the patient as a whole. This article discusses wound
      bed preparation and its clinical management components along with the principles
      of advanced wound care management at the present time. Management of tissue
      necrosis can be tailored according to the wound and local expertise. It ranges
      from simple to modern techniques like wet to dry dressing, enzymatic, biological
      and surgical debridement. Restoration of the bacterial balance is also an
      important element in managing chronic wounds that are critically colonized.
      Achieving a balance moist wound will hasten healing and correct biochemical
      imbalance by removing the excessive enzymes and growth factors. This can be
      achieved will multitude of dressing materials. The negative pressure wound
      therapy being one of the great breakthroughs. The progress and understanding on
      scientific basis of the wound bed preparation over the last two decades are
      discussed further in this article in the clinical perspectives.

PMID- 23162217
TI  - Evaluation of recombinant human platelet-derived growth factor as an agent for
      wound bed preparation in traumatic wounds.
AB  - BACKGROUND: In patients with life-threatening injuries, simple wounds requiring
      split-thickness skin grafts (SSG) often get neglected. These then need SSG once
      they are covered with granulation tissue through wound bed preparation.
      Traditionally, this is done by daily moist dressings. Recombinant human platelet
      derived growth factor (rhPDGF) has been shown to improve healing in chronic
      wounds. AIM: The present study was undertaken to compare the efficacy of rhPDGF
      in wound bed preparation with the current practice of daily saline dressings.
      SETTING AND DESIGN: A prospective randomised, single-blinded study was carried
      out for evaluation in traumatic wounds. MATERIALS AND METHODS: The patients were
      randomised and divided into a control group that was subjected to saline
      dressings and a test group that was treated with rhPDGF gel. Both the groups were
      then compared. The statistical analysis was carried out using SPSS 16.0 and the
      quantitative variables were analysed using unpaired "t" test, while the pre- and
      post-intervention effects were assessed using paired "t" test. The 95% CI values
      were also included. RESULTS: Of the 155 wounds studied, time taken for appearance
      of granulation tissue (in days) in the test group had a mean of 13.81 +/- 2.68,
      while that in the control group was 13.36 +/- 3.81 (P = 0.401). Complete re
      epithelialisation without discharge occurred in the control group with a mean
      value of 28.9 +/- 3.67 days, while that in the test group had a mean of 31.17 +/-
      4.82 days. CONCLUSION: There was no difference in wound healing between the
      patients treated with rhPDGF compared to those treated by conventional moist
      dressings.

PMID- 23162218
TI  - Medical simulation: Overview, and application to wound modelling and management.
AB  - Simulation in medical education is progressing in leaps and bounds. The need for
      simulation in medical education and training is increasing because of a) overall
      increase in the number of medical students vis-a-vis the availability of
      patients; b) increasing awareness among patients of their rights and consequent
      increase in litigations and c) tremendous improvement in simulation technology
      which makes simulation more and more realistic. Simulation in wound care can be
      divided into use of simulation in wound modelling (to test the effect of
      projectiles on the body) and simulation for training in wound management. Though
      this science is still in its infancy, more and more researchers are now devising
      both low-technology and high-technology (virtual reality) simulators in this
      field. It is believed that simulator training will eventually translate into
      better wound care in real patients, though this will be the subject of further
      research.

PMID- 23162219
TI  - Effect of static magnetic field on experimental dermal wound strength.
AB  - CONTEXT: An animal model. AIM: We sought to evaluate the effect of static
      magnetic fields on cutaneous wound healing. MATERIALS AND METHODS: Male Wistar
      rats were used. Wounds were created on the backs of all rats. Forty of these
      animals (M group) had NeFeB magnets placed in contact with the incisions, either
      parallel (Pa) and perpendicular (Pr) to the incision. The other 40 animals (sham
      [S] group) had nonmagnetized NeFeB bars placed in the same directions as the
      implanted animals. Half of the animals in each group were killed and assessed for
      healing on postoperative day 7 and the other half on postoperative day 14. The
      following assessments were done: gross healing, mechanical strength, and
      histopathology. STATISTICAL ANALYSIS USED: Intergroup differences were compared
      by using the Mann-Whitney U or t test. Values for P less than 0.05 were accepted
      as significant. RESULTS AND CONCLUSIONS: There were no differences between the
      magnetic and sham animals with respect to gross healing parameters. The
      mechanical strength was different between groups. On postoperative day 14, the
      MPr14 had significantly higher scores than the other groups. When static, high
      power, magnetic fields are placed perpendicular to the wound, increased wound
      healing occurs in the skin of the experimental model.

PMID- 23162220
TI  - Cellular events and biomarkers of wound healing.
AB  - Researchers have identified several of the cellular events associated with wound
      healing. Platelets, neutrophils, macrophages, and fibroblasts primarily
      contribute to the process. They release cytokines including interleukins (ILs)
      and TNF-alpha, and growth factors, of which platelet-derived growth factor (PDGF)
      is perhaps the most important. The cytokines and growth factors manipulate the
      inflammatory phase of healing. Cytokines are chemotactic for white cells and
      fibroblasts, while the growth factors initiate fibroblast and keratinocyte
      proliferation. Inflammation is followed by the proliferation of fibroblasts,
      which lay down the extracellular matrix. Simultaneously, various white cells and
      other connective tissue cells release both the matrix metalloproteinases (MMPs)
      and the tissue inhibitors of these metalloproteinases (TIMPs). MMPs remove
      damaged structural proteins such as collagen, while the fibroblasts lay down
      fresh extracellular matrix proteins. Fluid collected from acute, healing wounds
      contains growth factors, and stimulates fibroblast proliferation, but fluid
      collected from chronic, nonhealing wounds does not. Fibroblasts from chronic
      wounds do not respond to chronic wound fluid, probably because the fibroblasts of
      these wounds have lost the receptors that respond to cytokines and growth
      factors. Nonhealing wounds contain high levels of IL1, IL6, and MMPs, and an
      abnormally high MMP/TIMP ratio. Clinical examination of wounds inconsistently
      predicts which wounds will heal when procedures like secondary closure are
      planned. Surgeons therefore hope that these chemicals can be used as biomarkers
      of wounds which have impaired ability to heal. There is also evidence that the
      application of growth factors like PDGF will help the healing of chronic,
      nonhealing wounds.

PMID- 23162221
TI  - An update review of stem cell applications in burns and wound care.
AB  - The ultimate goal of the treatment of cutaneous burns and wounds is to restore
      the damaged skin both structurally and functionally to its original state. Recent
      research advances have shown the great potential of stem cells in improving the
      rate and quality of wound healing and regenerating the skin and its appendages.
      Stem cell-based therapeutic strategies offer new prospects in the medical
      technology for burns and wounds care. This review seeks to give an updated
      overview of the applications of stem cell therapy in burns and wound management
      since our previous review of the "stem cell strategies in burns care".

PMID- 23162222
TI  - Role of stem cells in the management of chronic wounds.
AB  - Chronic wounds continue to be a major challenge for the medical profession, and
      plastic surgeons are frequently called in to help in the management of such
      wounds. Apart from the obvious morbidity to the patient, these problem wounds can
      be a major drain on the already scarce hospital resources. Sometimes, these
      chronic wounds can be more taxing than the underlying disease itself. Although
      many newer methods are available to handle such situations, the role of stem
      cells in the management of such wounds is an exciting area that needs to be
      explored further. A review of literature has been done regarding the role of stem
      cells in the management of chronic wounds. The abnormal pathology in such wounds
      is discussed and the possible role of stem cells for optimal healing in such
      cases would be detailed.

PMID- 23162224
TI  - Chronic lower limb wounds evoke systemic response of the lymphatic (immune)
      system.
AB  - Wound healing should not be considered as a process limited only to the damaged
      tissues. It is always accompanied by an intensive local immune response and in
      advanced stages, the systemic lymphatic (immune) structure. In this review we
      present evidence from our own studies as well as pertinent literature on the role
      of skin and subcutaneous tissue lymphatics at the wound site and of transport of
      antigens along with collecting afferent lymphatics to the lymph nodes. We also
      speculate the role of lymph nodes in raising cohorts of bacterial and own tissue
      antigen-specific lymphocytes and their participation in healing and not
      infrequently evoking uncontrolled chronic immune reaction causing a delay of
      healing. It is also speculated as to why there is a rapid response of lymph node
      cells to microbial antigens and tolerance to damaged-tissue-derived antigens
      occurs.

PMID- 23162223
TI  - Pressure ulcers: Back to the basics.
AB  - Pressure ulcer in an otherwise sick patient is a matter of concern for the care
      givers as well as the medical personnel. A lot has been done to understand the
      disease process. So much so that USA and European countries have established
      advisory panels in their respective continents. Since the establishment of these
      organizations, the understanding of the pressure ulcer has improved
      significantly. The authors feel that the well documented and well publicized
      definition of pressure ulcer is somewhat lacking in the correct description of
      the disease process. Hence, a modified definition has been presented. This
      disease is here to stay. In the process of managing these ulcers the basic
      pathology needs to be understood well. Pressure ischemia is the main reason
      behind the occurrence of ulceration. Different extrinsic and intrinsic factors
      have been described in detail with review of literature. There are a large number
      of risk factors causing ulceration. The risk assessment scales have eluded the
      surgical literature and mostly remained in nursing books and websites. These
      scales have been reproduced for completion of the basics on decubitus ulcer. The
      classification of the pressure sores has been given in a comparative form to
      elucidate that most of the classifications are the same except for minor
      variations. The management of these ulcers is ever evolving but the age old
      saying of "prevention is better than cure" suits this condition the most.

PMID- 23162225
TI  - Management of ulcers in lymphoedematous limbs.
AB  - Lymphoedema is a progressive condition that can have a marked physical and
      psychological impact on affected patients and significantly reduce the quality of
      life. The ulcers on chronic lymphoedema patient, which often also makes it
      impossible for them to work. If left untreated, tends to progress or worsen.
      Ulcers in lymphoedema patients, therefore, represent not only a medical but also
      a psychological problem. The treatment is often regarded as being worse than it
      actually is. In our study of more than 25 years shows around 10% cases are due to
      chronic lymphodema. Ulcers of chronic lymphoedema are classified into four stages
      according to their presentation. Their management depends upon their stage of
      presentation. Patients with chronic lymphoedema and ulceration require a
      different approach to treatment. The specific issues associated with managing the
      patient with lymphoedematous ulceration include, limb shape distortion i.e.,
      elephantiasis, care of the skin creases and folds, and swelling of the toes and
      fore foot. Stage I ulcers will heal with conservative treatment without any
      surgical intervention. Stage II ulcers needs debridement of the wound and split
      thickness skin grafting. The most difficult to treat are the stage III and IV
      ulcers, due to associated skin changes and reduced vascularity. These cases need
      debulking along with excision of the ulcer. In order to prevent recurrence of the
      ulcer in all the four stages needs prolonged follow-up and limb care.

PMID- 23162227
TI  - Compression therapy for ulcers: The science and the art.
AB  - INTRODUCTION: Chronic ulcers are characterized by being resistant to all forms of
      treatment. Recent improvement in compression techniques, notably use of
      multilayer bandaging has created a need for a re-look into it's use. MATERIALS
      AND METHODS: The authors present two case reports of successful management of
      chronic ulcers using compression through bandaging where all other forms of
      treatment had failed. This is followed by a review of literature based on
      previous articles as well as more recent ones found through Pubmed. CONCLUSION:
      It is suggested that, at least in India, compression through proper multilayer
      bandaging, should be a choice far higher in the treatment ladder than so
      previously. However, if the technique is improper, it may be harmful so the
      option is to be exercised with care and only by those who have received adequate
      training. The need of a team approach, and alongside, wider introduction of more
      and better training facilities for therapists and nurses is underlined.

PMID- 23162228
TI  - Wound coverage considerations for defects of the lower third of the leg.
AB  - Anatomical features of the lower third of the leg like subcutaneous bone
      surrounded by tendons with no muscles, vessels in isolated compartments with
      little intercommunication between them make the coverage of the wounds in the
      region a challenging problem. Free flaps continue to be the gold standard for the
      coverage of lower third leg wounds because of their ability to cover large
      defects with high success rates and feasibility of using it in acute situations
      by choosing distant recipient vessels. Reverse flow flaps are more useful for the
      coverage of the ankle and foot defects than lower third leg defects. The
      perforators in the lower third leg on which these flaps are based are often
      damaged during the injury. In medium-sized defects of less than 50 cm(2) size,
      local transposition flaps, perforator flaps, or propeller flaps can be used.
      Preoperative identification by the Doppler is essential before embarking on these
      flaps. Of the muscle flaps, the peroneus brevis flap can be used in selected
      cases with small defects. In spite of all recent developments, cross-leg flaps
      continue to remain as a useful technique. In rare occasions when other flaps are
      not possible or when other options fail it can be a life boat. In the author's
      practice free flaps continue to be the first choice for coverage of wounds in the
      lower third leg with gracilis muscle flap for small and medium defects,
      latissimus dorsi muscle flap for large defects and anterolateral thigh flap when
      a skin flap is preferred.

PMID- 23162226
TI  - Venous ulcers of the lower limb: Where do we stand?
AB  - Venous ulcers are the most common ulcers of the lower limb. It has a high
      morbidity and results in economic strain both at a personal and at a state level.
      Chronic venous hypertension either due to primary or secondary venous disease
      with perforator paucity, destruction or incompetence resulting in reflux is the
      underlying pathology, but inflammatory reactions mediated through leucocytes,
      platelet adhesion, formation of pericapillary fibrin cuff, growth factors and
      macromolecules trapped in tissue result in tissue hypoxia, cell death and
      ulceration. Duplex scan with colour flow is the most useful investigation for
      venous disease supplying information about patency, reflux, effects of proximal
      and distal compression, Valsalva maneuver and effects of muscle contraction. Most
      venous disease can be managed conservatively by leg elevation and compression
      bandaging. Drugs of proven benefit in venous disease are pentoxifylline and
      aspirin, but they work best in conjunction with compression therapy. Once
      ulceration is chronic or the patient does not respond to or cannot maintain
      conservative regime, surgical intervention treating the underlying venous
      hypertension and cover for the ulcer is necessary. The different modalities like
      sclerotherapy, ligation and stripping of superficial varicose veins, endoscopic
      subfascial perforator ligation, endovenous laser or radiofrequency ablation have
      similar long-term results, although short-term recovery is best with
      radiofrequency and foam sclerotherapy. For deep venous reflux, surgical
      modalities include repair of incompetent venous valves or transplant or
      transposition of a competent vein segment with normal valves to replace a post
      thrombotic destroyed portion of the deep vein.

PMID- 23162229
TI  - Improved wound management by regulated negative pressure-assisted wound therapy
      and regulated, oxygen- enriched negative pressure-assisted wound therapy through
      basic science research and clinical assessment.
AB  - Regulated negative pressure-assisted wound therapy (RNPT) should be regarded as a
      state-of-the-art technology in wound treatment and the most important physical,
      nonpharmaceutical, platform technology developed and applied for wound healing in
      the last two decades. RNPT systems maintain the treated wound's environment as a
      semi-closed, semi-isolated system applying external physical stimulations to the
      wound, leading to biological and biochemical effects, with the potential to
      substantially influence wound-host interactions, and when properly applied may
      enhance wound healing. RNPT is a simple, safe, and affordable tool that can be
      utilized in a wide range of acute and chronic conditions, with reduced need for
      complicated surgical procedures, and antibiotic treatment. This technology has
      been shown to be effective and safe, saving limbs and lives on a global scale.
      Regulated, oxygen-enriched negative pressure-assisted wound therapy (RO-NPT) is
      an innovative technology, whereby supplemental oxygen is concurrently
      administered with RNPT for their synergistic effect on treatment and prophylaxis
      of anaerobic wound infection and promotion of wound healing. Understanding the
      basic science, modes of operation and the associated risks of these technologies
      through their fundamental clinical mechanisms is the main objective of this
      review.

PMID- 23162230
TI  - Exploiting potency of negative pressure in wound dressing using limited access
      dressing and suction-assisted dressing.
AB  - Role of negative pressure dressing and moist wound healing are well established
      in the treatment of both acute and chronic wounds with certain advantages and
      disadvantages in both the techniques. Both these techniques prevents wound
      colonization, but the negative pressure dressing method has proved to have a
      greater potency to remove secretions, prevent wound invasion and eradication
      established infection. In both these techniques there is no accessibility to
      wound environment. Limited access dressing (LAD) is a moist wound dressing with
      negative pressure. It provides limited access to the wound through two small
      ports for both dressers and pathogens. The LAD design has notable advantages like
      wound isolation that reduces chance of wound colonization and safe disposal of
      infected materials (important factor to reduce hospital-acquired infections),
      while avoiding some major disadvantages such as opacity of dressing materials,
      inaccessible offensive smelling wound environment, and relatively high treatment
      costs. In LAD a definite intermittent negative pressure regimen is followed. The
      intermittent negative pressure (cycle of 30 minutes suction and 31/2 hours rest)
      is effective. Overall, the LAD is a safe and effective alternative to
      conventional dressing methods. LAD is an excellent research tool for wound
      healing as frequent/continuous record of wound healing is possible without
      disturbing the wound healing process. LAD is an effective dressing for limb
      salvage in cases of acute and chronic complex wounds. Leech effect prevents wound
      related systematic response syndrome and sepsis. Suction-assisted dressing (SAD)
      is a combination of semiocclusive dressing with negative pressure. It works by
      removal of fluids by intermittent (like LAD) negative pressure and preventing
      bacterial invasion. SAD is especially advantageous where soakage is less, there
      is no dead tissue covering the wound (e.g., following skin grafting), superficial
      skin wounds (e.g., donor area) and also where LAD is technically difficult to
      apply over circumferential trunk and neck dressings under anesthesia.

PMID- 23162231
TI  - Hyperbaric oxygen and wound healing.
AB  - Hyperbaric oxygen therapy (HBOT) is the use of 100% oxygen at pressures greater
      than atmospheric pressure. Today several approved applications and indications
      exist for HBOT. HBOT has been successfully used as adjunctive therapy for wound
      healing. Non-healing wounds such as diabetic and vascular insufficiency ulcers
      have been one major area of study for hyperbaric physicians where use of HBOT as
      an adjunct has been approved for use by way of various studies and trials. HBOT
      is also indicated for infected wounds like clostridial myonecrosis, necrotising
      soft tissue infections, Fournier's gangrene, as also for traumatic wounds, crush
      injury, compartment syndrome, compromised skin grafts and flaps and thermal
      burns. Another major area of application of HBOT is radiation-induced wounds,
      specifically osteoradionecrosis of mandible, radiation cystitis and radiation
      proctitis. With the increase in availability of chambers across the country, and
      with increasing number of studies proving the benefits of adjunctive use for
      various kinds of wounds and other indications, HBOT should be considered in these
      situations as an essential part of the overall management strategy for the
      treating surgeon.

PMID- 23162232
TI  - Management of radiation wounds.
AB  - Radiotherapy forms an integral part in cancer treatment today. It is used alone
      or in combination with surgery and chemotherapy. Although radiotherapy is useful
      to effect tumour death, it also exerts a deleterious effect on surrounding normal
      tissues. These effects are either acute or can manifest months or years after the
      treatment. The chronic wounds are a result of impaired wound healing. This
      impairment results in fibrosis, nonhealing ulcers, lymphoedema and radionecrosis
      amongst others. This article will discuss the pathophysiology in brief, along
      with the manifestations of radiation-induced injury and the treatment available
      currently.

PMID- 23162233
TI  - Reconstructive challenges in war wounds.
AB  - War wounds are devastating with extensive soft tissue and osseous destruction and
      heavy contamination. War casualties generally reach the reconstructive surgery
      centre after a delayed period due to additional injuries to the vital organs.
      This delay in their transfer to a tertiary care centre is responsible for
      progressive deterioration in wound conditions. In the prevailing circumstances, a
      majority of war wounds undergo delayed reconstruction, after a series of
      debridements. In the recent military conflicts, hydrosurgery jet debridement and
      negative pressure wound therapy have been successfully used in the preparation of
      war wounds. In war injuries, due to a heavy casualty load, a faster and reliable
      method of reconstruction is aimed at. Pedicle flaps in extremities provide rapid
      and reliable cover in extremity wounds. Large complex defects can be
      reconstructed using microvascular free flaps in a single stage. This article
      highlights the peculiarities and the challenges encountered in the reconstruction
      of these ghastly wounds.

PMID- 23162234
TI  - Trophic ulcers-Practical management guidelines.
AB  - The management of patients with trophic ulcers and their consequences is
      difficult not only because it is a recurrent and recalcitrant problem but also
      because the pathogenesis of the ulcer maybe different in each case. Methodically
      and systematically evaluating and ruling out concomitant pathologies helps to
      address each patient's specific needs and hence bring down devastating
      complications like amputation. With incidence of diabetes being high in our
      country, and leprosy being endemic too the consequences of neuropathy and
      angiopathy are faced by most wound care specialists. This article presents a
      review of current English literature available on this subject. The search words
      were entered in PubMed central and appropriate abstracts reviewed. Relevant full
      text articles were retrieved and perused. Cross references from these articles
      were also reviewed. Based on these articles and the authors' experiences
      algorithms for management have been presented to facilitate easier understanding.
      It is hoped that the information presented in this article will help in
      management of this recalcitrant problem.

PMID- 23162235
TI  - The management of perineal wounds.
AB  - Management of perineal wounds can be very frustrating as these invariably get
      contaminated from the ano-genital tracts. Moreover, the apparent skin defect may
      be associated with a significant three dimensional dead space in the pelvic
      region. Such wounds are likely to become chronic and recalcitrant if appropriate
      wound management is not instituted in a timely manner. These wounds usually
      result after tumor excision, following trauma or as a result of infective
      pathologies like hideradenitis suppurativa or following thermal burns. Many
      options are available for management of perineal wounds and these have been
      discussed with illustrative case examples. A review of literature has been done
      for listing commonly instituted options for management of the wounds in perineum.

PMID- 23162236
TI  - Burn wound: How it differs from other wounds?
AB  - Management of burn injury has always been the domain of burn specialists. Since
      ancient time, local and systemic remedies have been advised for burn wound
      dressing and burn scar prevention. Management of burn wound inflicted by the
      different physical and chemical agents require different regimes which are poles
      apart from the regimes used for any of the other traumatic wounds. In extensive
      burn, because of increased capillary permeability, there is extensive loss of
      plasma leading to shock while whole blood loss is the cause of shock in other
      acute wounds. Even though the burn wounds are sterile in the beginning in
      comparison to most of other wounds, yet, the death in extensive burns is mainly
      because of wound infection and septicemia, because of the immunocompromised
      status of the burn patients. Eschar and blister are specific for burn wounds
      requiring a specific treatment protocol. Antimicrobial creams and other dressing
      agents used for traumatic wounds are ineffective in deep burns with eschar. The
      subeschar plane harbours the micro-organisms and many of these agents are not
      able to penetrate the eschar. Even after complete epithelisation of burn wound,
      remodelling phase is prolonged. It may take years for scar maturation in burns.
      This article emphasizes on how the pathophysiology, healing and management of a
      burn wound is different from that of other wounds.

PMID- 23162237
TI  - A comparative study of the effect of different topical agents on burn wound
      infections.
AB  - BACKGROUND: Topical agents are used to treat burn wound infections. AIMS AND
      OBJECTIVE: The present work was aimed to find out the in vitro efficacy of
      different topical agents against burn wound pathogens. SETTINGS AND DESIGN:
      Randomly selected gram-positive (29) and gram-negative bacterial (119) isolates
      from burn wound cases admitted in burn unit of Choithram Hospital and Research
      Centre, Indore, were included in the in vitro activity testing for silver
      nitrate, silver sulphadiazine (SSD), chlorhexidine, cetrimide, nitrofuran,
      soframycin, betadine, benzalkonium chloride and honey by growth inhibition on
      agar medium. MATERIALS AND METHODS: Multidrug-resistant isolates of gram-positive
      and gram-negative bacteria were checked for different topical agents. 1% topical
      agent was mixed with Mueller-Hinton agar. Two microlitres of bacterial suspension
      adjusted to 0.5 McFarland turbidity standard was spread over the topical agent
      containing plates. The plates without the topical agent were used as control
      plates. The plates were incubated for 48 h at 37 degrees C. RESULTS: SSD
      (148/148), silver nitrate (148/148) and chlorhexidine (148/148) showed excellent
      activity against all the pathogens. Neosporin had poor activity against
      Pseudomonas aeruginosa, (4/44) Proteus spp. (2/4) and group D streptococci (1/4).
      Betadine did not show activity against the bacterial isolates in the presence of
      organic matter. Honey did not exert any antimicrobial activity under the study
      conditions. CONCLUSION: SSD, silver nitrate and chlorhexidine have excellent
      activity against all the bacterial pathogens and could be used empirically, while
      identification of the infective agent is required for selecting the alternative
      topical agents such as nitrofuran, soframycin, and benzalkonium chloride.

PMID- 23162239
TI  - Skin substitutes: An Indian perspective.
AB  - There have been numerous alternatives developed to replace skin. These can either
      be permanent substitutes or temporary substitutes, which need to be replaced
      later by autologous grafts. These have been tried in recent times as an attempt
      to reduce the need or in the case of permanent substitutes ,altogether replace
      autologous skin grafts. However till date no ideal skin substitute has been
      developed. Various factors have to be considered while choosing one of these
      substitutes. In a developing country like India awareness and availability of
      these skin substitutes is not adequate considering the volume of cases that
      require this modality of treatment. Also there are skin substitutes developed in
      our country that need to be highlighted. This article is an attempt to review the
      vast array of skin substitutes that have been developed and consider their
      utility and feasibility for developing countries.

PMID- 23162238
TI  - Recent advances in topical wound care.
AB  - There are a wide variety of dressing techniques and materials available for
      management of both acute wounds and chronic non-healing wounds. The primary
      objective in both the cases is to achieve a healed closed wound. However, in a
      chronic wound the dressing may be required for preparing the wound bed for
      further operative procedures such as skin grafting. An ideal dressing material
      should not only accelerate wound healing but also reduce loss of protein,
      electrolytes and fluid from the wound, and help to minimize pain and infection.
      The present dictum is to promote the concept of moist wound healing. This is in
      sharp contrast to the earlier practice of exposure method of wound management
      wherein the wound was allowed to dry. It can be quite a challenge for any
      physician to choose an appropriate dressing material when faced with a wound.
      Since wound care is undergoing a constant change and new products are being
      introduced into the market frequently, one needs to keep abreast of their effect
      on wound healing. This article emphasizes on the importance of assessment of the
      wound bed, the amount of drainage, depth of damage, presence of infection and
      location of wound. These characteristics will help any clinician decide on which
      product to use and where,in order to get optimal wound healing. However, there
      are no 'magical dressings'. Dressings are one important aspect that promotes
      wound healing apart from treating the underlying cause and other supportive
      measures like nutrition and systemic antibiotics need to be given equal
      attention.

PMID- 23162242
TI  - Telemedicine for wound management.
AB  - The escalating physiological, psychological, social and financial burdens of
      wounds and wound care on patients, families and society demand the immediate
      attention of the health care sector. Many forces are affecting the changes in
      health care provision for patients with chronic wounds, including managed care,
      the limited number of wound care therapists, an increasingly ageing and disabled
      population, regulatory and malpractice issues, and compromised care. The
      physician is also faced with a number of difficult issues when caring for chronic
      wound patients because their conditions are time consuming and high risk,
      represent an unprofitable part of care practice and raise issues of liability.
      Telemedicine enhances communication with the surgical wound care specialist.
      Digital image for skin lesions is a safe, accurate and cost-effective referral
      pathway. The two basic modes of telemedicine applications, store and forward
      (asynchronous transfer) and real-time transmission (synchronous transfer, e.g.
      video conference), are utilized in the wound care setting. Telemedicine
      technology in the hands of an experienced physician can streamline management of
      a problem wound. Although there is always an element of anxiety related to
      technical change, the evolution of wound care telemedicine technology has
      demonstrated a predictable maturation process.

PMID- 23162241
TI  - Abnormal pigmentation within cutaneous scars: A complication of wound healing.
AB  - Abnormally pigmented scars are an undesirable consequence of cutaneous wound
      healing and are a complication every single individual worldwide is at risk of.
      They present a challenge for clinicians, as there are currently no definitive
      treatment options available, and render scars much more noticeable making them
      highly distressing for patients. Despite extensive research into both wound
      healing and the pigment cell, there remains a scarcity of knowledge surrounding
      the repigmentation of cutaneous scars. Pigment production is complex and under
      the control of many extrinsic and intrinsic factors and patterns of scar
      repigmentation are unpredictable. This article gives an overview of human skin
      pigmentation, repigmentation following wounding and current treatment options.

PMID- 23162240
TI  - Development of tissue bank.
AB  - The history of tissue banking is as old as the use of skin grafting for
      resurfacing of burn wounds. Beneficial effects of tissue grafts led to wide
      spread use of auto and allograft for management of varied clinical conditions
      like skin wounds, bone defects following trauma or tumor ablation. Availability
      of adequate amount of tissues at the time of requirement was the biggest
      challenge that forced clinicians to find out techniques to preserve the living
      tissue for prolonged period of time for later use and thus the foundation of
      tissue banking was started in early twentieth century. Harvesting, processing,
      storage and transportation of human tissues for clinical use is the major
      activity of tissue banks. Low temperature storage of processed tissue is the best
      preservation technique at present. Tissue banking organization is a very complex
      system and needs high technical expertise and skilled personnel for proper
      functioning in a dedicated facility. A small lapse/deviation from the established
      protocol leads to loss of precious tissues and or harm to recipients as well as
      the risk of transmission of deadly diseases and tumors. Strict tissue transplant
      acts and stringent regulations help to streamline the whole process of tissue
      banking safe for recipients and to community as whole.

PMID- 23162243
TI  - Wound care with traditional, complementary and alternative medicine.
AB  - Wound care is constantly evolving with the advances in medicine. Search for the
      ideal dressing material still continues as wound care professionals are faced
      with several challenges. Due to the emergence of multi-resistant organisms and a
      decrease in newer antibiotics, wound care professionals have revisited the
      ancient healing methods by using traditional and alternative medicine in wound
      management. People's perception towards traditional medicine has also changed and
      is very encouraging. The concept of moist wound healing has been well accepted
      and traditional medicine has also incorporated this method to fasten the healing
      process. Several studies using herbal and traditional medicine from different
      continents have been documented in wound care management. Honey has been used
      extensively in wound care practice with excellent results. Recent scientific
      evidences and clinical trials conducted using traditional and alternative
      medicine in wound therapy holds good promise in the future.

PMID- 23162245
TI  - A novel and accurate technique of photographic wound measurement.

PMID- 23162244
TI  - A novel and accurate technique of photographic wound measurement.
AB  - CONTEXT: Wound measurement is an important aspect of wound management. Though
      there are many techniques to measure wounds, most of them are either cumbersome
      or too expensive. AIMS: To introduce a simple and accurate technique by which
      wounds can be accurately measured. SETTINGS AND DESIGN: This is a comparative
      study of 10 patients whose wounds were measured by three techniques, i.e. ruler,
      graph and our technique. MATERIALS AND METHODS: The graph method was taken as the
      control measurement. The extent of deviation in wound measurements with our
      method was compared with the standard technique. The statistical analysis used
      was ANOVA. RESULTS: The ruler method was highly inaccurate and overestimated the
      wound size by nearly 50%. Our technique remained consistent and accurate with the
      percentage of over or underestimation being 2-4% in comparison with the graph
      method. CONCLUSIONS: This technique is simple and accurate and is an inexpensive
      and non-invasive method to accurately measure wounds.

PMID- 23162246
TI  - PNDT and other issues.

PMID- 23162247
TI  - Bipolar radiofrequency-induced thermotherapy of great saphenous vein: Our initial
      experience.
AB  - The incidence of varicose veins in lower limbs is increasing in the Indian
      subcontinent. With the advent of radiofrequency ablation (RFA), an effective
      minimally invasive technique is now available to treat varicose veins. RFA can be
      performed with either unipolar or bipolar probes. We present a simple technique
      for bipolar radiofrequency-induced thermotherapy of the great saphenous vein.
      This can be a safe and effective alternative to surgical procedures.

PMID- 23162248
TI  - Technical Note: Thoracic duct embolization for treatment of chylothorax: A novel
      guidance technique for puncture using combined MRI and fluoroscopy.
AB  - Thoracic duct embolization (TDE) is an established radiological interventional
      procedure for thoracic duct injuries. Traditionally, it is done under
      fluoroscopic guidance after opacifying the thoracic duct with bipedal
      lymphangiography. We describe our experience in usinga heavily T2W sequence for
      guiding thoracic duct puncture and direct injection of glue through the puncture
      needle without cannulating the duct.

PMID- 23162249
TI  - Noninvasive treatment of focal adenomyosis with MR-guided focused ultrasound in
      two patients.
AB  - Adenomyosis is a common benign gynecological disorder presenting with
      dysmenorrhea, menorrhagia, and pressure symptoms. Magnetic resonance imaging
      guided focused ultrasound surgery (MRgFUS) utilizes precisely focused USG waves
      to generate and maintain high temperatures within the targeted tissue to achieve
      protein denaturation and coagulative necrosis. The heat generated is monitored
      using MRI images acquired in real-time in three planes. We present two cases of
      focal adenomyosis treated with MRgFUS showing good symptomatic relief at 3 and 6
      months follow-up.

PMID- 23162250
TI  - Pictorial essay: Acute neurological complications in children with acute
      lymphoblastic leukemia.
AB  - Acute lymphoblastic leukemia (ALL) is the commonest childhood malignancy with
      high cure rates due to recent advances in central nervous system (CNS)
      prophylaxis. The disease per se, as well as the prophylactic therapy, predisposes
      the child to complications such as cerebrovascular events, infections, drug
      toxicities, etc. The purpose of this study is to highlight the pathophysiology
      and the imaging features (with appropriate examples) of these complications and
      to propose a diagnostic algorithm based on MRI. Interpreting these scans in the
      light of clinical inputs very often helps the radiologist reach an appropriate
      diagnosis and help treatment and management.

PMID- 23162251
TI  - Diffusion-weighted MRI in acute posterior ischemic optic neuropathy.
AB  - Blindness following surgery, especially cardiac surgery, has been reported
      sporadically, the most common cause being ischemic optic neuropathy. The role of
      MRI in the diagnosis of this condition is not well established. We present a case
      of postoperative posterior ischemic optic neuropathy that was diagnosed on
      diffusion-weighted MRI.

PMID- 23162252
TI  - Case Series: Long segment extra-arachnoid fluid collections: Role of dynamic CT
      myelography in diagnosis and treatment planning.
AB  - We report five patients in whom spinal MRI revealed extra-arachnoid fluid
      collections. These spinal fluid collections most likely resulted from
      accumulation of cerebrospinal fluid (CSF) from a dural leak. The patients
      presented with either compressive myelopathy due to the cyst or superficial
      siderosis (SS). All of these fluid collections were long segment, and MRI
      demonstrated the fluid collections but not the exact site of leak. Dynamic CT
      myelogram demonstrated the site of leak and helped in the management of these
      complicated cases. Moreover, we also found that the epicenter of the fluid
      collection on MRI was different from the location of the leak on a dynamic CT
      myelogram. Knowledge of these associations can be helpful when selecting the
      imaging studies to facilitate diagnosis and treatment.

PMID- 23162253
TI  - Understanding the natural history of focal nodular hyperplasia in the liver with
      MRI.
AB  - AIMS: To determine the incidence of natural growth or regression of focal nodular
      hyperplasia (FNH) in the liver. MATERIAL AND METHODS: We retrospectively included
      120 consecutive patients who were diagnosed to have FNH on MRI. The mean follow
      up duration was 19 months (range: 6-64 months). There were 25 men and 95 women
      (age range: 18-80 years; mean: 45 years). There were 167 FNH lesions in the 120
      patients. MRI images were retrospectively reviewed for interval growth or
      regression of FNH. The maximum size of the lesions was measured on axial arterial
      phase images of the initial and the last MRI examinations. An interval increase
      or decrease in diameter of over 10% of the initial diameter was considered as
      positive growth or regression, respectively. The use of Oral contraceptives was
      also documented. RESULTS: Interval growth was seen in 25/167 nodules (15%) over 7
      48 months (mean: 21 months), with increase in size of 0.2-1.7 cm (mean: 0.6 cm)
      and percentage change of 10.5-340% (mean: 64%). Interval regression was seen in
      13/167 (8%) of nodules over 7-63 months (mean: 22 months), with decrease in size
      of 0.2-0.9 cm (mean: 0.5 cm) and percentage change of 10.4-60% (mean: 24%).Five
      of 17 (29%) female patients with growing FNH and 25/78 (32%) female patients with
      non-growing FNH had a history of intake of oral contraceptives (P=0.83).
      CONCLUSIONS: Although FNH is benign and of no clinical significance, a
      substantial percentage of FNH shows interval growth or regression on long-term
      follow-up with MRI.

PMID- 23162254
TI  - Emoticons for radiologist.

PMID- 23162255
TI  - The sonologist and the sex ratio: Who is to blame?

PMID- 23162256
TI  - Guidelines for ultrasound owners and owners of clinics, diagnostic centres,
      nursing homes and hospitals.
AB  - These are guidelines that are required for ultrasound owners for registration and
      use of ultrasound machines and are applicable across India. A brief description
      of the violations and penalties has also been listed.

PMID- 23162257
TI  - Social aspects of the declining girl ratios.
AB  - THIS ARTICLE IS A BRIEF OVERVIEW OF THE PROBLEMS FACED BY INDIAN WOMEN SINCE
      DECADES OF SOCIAL INTOLERANCE THAT HAS LED TO THE GULF IN THE MALE: female sex
      ratio in our country.

PMID- 23162258
TI  - The PC-PNDT act in a nutshell.

PMID- 23162259
TI  - Moving forward for the girl child.

PMID- 23162261
TI  - Important points in the PC-PNDT Act.

PMID- 23162260
TI  - A perspective on the PCPNDT Act.
AB  - BACKGROUND: An important modern diagnostic tool, used for monitoring pregnancy
      and genetic defects; the ultrasound machine, has also become a selective killer
      of the female child. The male child preference in India was responsible for
      female infanticides in the past. With easy availability and accessibility of USG,
      a shift has occurred from infanticide to feticide, although female infanticides
      still continue. In the process doctors are blamed as "merchants of death". Peeved
      and pressed by national and internal agencies for the declining female child
      ratio (0-6 years), the Government of India reacted by enacting a stringent PC
      PNDT Act almost solely aimed at doctors to prevent them from advertising and
      disclosing the sex of the fetus to the pregnant woman or her relatives. Since the
      enactment, hundreds of cases have been launched against the doctors. AIMS: 1. In
      order to stand up to the law important sections and rules of the PC-PNDT Act have
      been analyzed for the benefit of our colleagues. 2. The Indian legal system rests
      the burden of proof on the prosecution. In two sections of The Act, these have
      been done away with. Instead, the accused doctor has to prove himself innocent.
      Therefore a demand has been made to make suitable amendments to The Act in this
      regard. 3. The inclusion of column numbers 9-19 in the form 'F' is not relevant
      for USG clinics/ imaging centers; inaccurate filling of which may attract a
      prison sentence of 3 years. This irrelevance has to be deleted. 4. Some
      suggestions.

PMID- 23162262
TI  - The PC-PNDT act: An attempt to gender equality: Radiologists' perspective.

PMID- 23162263
TI  - Radiologists: The latest victims of an unfair system.

PMID- 23162264
TI  - Relief from high court against restriction imposed by appropriate authority under
      PC-PNDT act on number of ultrasound centers visited by a Sonologist.

PMID- 23162265
TI  - Deflazacort in comparison to other steroids for nephrotic syndrome.
AB  - Patients with nephrotic syndrome require steroids for long time and sometimes
      repeatedly resulting in various adverse effects. Deflazacort (DFZ) had been
      described as equally effective and with fewer side effects as compared with other
      steroids. This review evaluates the literature on efficacy and toxicity of DFZ as
      compared with other therapies for nephrotic syndrome. A systematic review of
      Pubmed database and Cochrane Central Register of Controlled Trials with last
      search date of 20(th) April 2011. Search terms included "nephrotic AND
      deflazacort" without any limitations. Randomized control trials comparing DFZ vs
      placebo or other therapies in subjects with nephrotic syndrome were included. Two
      authors extracted data independently. Three studies meet inclusion criteria and
      data were synthesized qualitatively. The limited evidence suggested that DFZ
      appeared to be equally effective in inducing remission or decreasing proteinuria
      in patients with nephrotic syndrome. It caused significantly less decrease in
      bone mineral content (BMC) in spine as compared with prednisolone. The results
      related to weight change, blood pressure change, Cushingoid symptoms, and urinary
      calcium excretion were inconsistent between included studies. By reviewing the
      available limited evidence, DFZ appears to be of similar efficacy for nephrotic
      patients, but there were inconsistent results regarding side effect profile of
      DFZ as compared with other steroids except for decrease in BMC where DFZ was
      better. There is need for larger randomized controlled trials to evaluate
      effectiveness and adverse effect profile of DFZ as compared with other steroids
      in nephrotic syndrome.

PMID- 23162266
TI  - Periodontal status in patients undergoing hemodialysis.
AB  - The aim of the study was to assess the periodontal status of patients among group
      of patients receiving hemodialysis in two super specialty renal institutes in the
      state of Gujarat. A cross-sectional study of 304 subjects, 152 subjects each in
      dialysis, and control group was conducted. Oral hygiene status was assessed using
      a Simplified Oral Hygiene Index, and periodontal status was assessed using the
      Community Periodontal Index (CPI) and Loss of Attachment (LOA) as per WHO
      methodology 1997. The dialysis group had poor oral hygiene than the control group
      (P<0.001). There was high severity of periodontitis in the dialysis group as
      compared with the control group (P<0.001). None of the subjects had healthy
      periodontium. There was high severity of periodontitis (for both in terms of CPI
      and LOA) in the dialysis group as compared with control group that was found to
      be statistically highly significant (P<0.001). However, no statistically
      significant difference was observed (P>0.05) when the intergroup comparison for
      CPI and LOA were made among the subgroups according to the duration of dialysis.
      Periodontal disease is prevalent in chronic renal failure patients who showed the
      unacceptable level of oral hygiene and hence there is need for oral health
      promotion and preventive programs among the patients receiving dialysis.

PMID- 23162267
TI  - A multicenter cross-sectional study of mental and physical health depression in
      MHD patients.
AB  - Depression is ranked fourth among the disabling diseases affecting people
      worldwide and is the most common psychological problem in patients with End Stage
      Renal Disease (ESRD). The aim of this study is to assess the physical and
      emotional health status of renal dialysis patients, based on the SF-36 scale in
      relation to their economic status. Sixty maintenance hemodialysis patients, with
      a mean age of 40+/-13 years were included in this cross-sectional study using the
      SF-36 scale. It comprises 36 questions regarding physical and mental functions,
      body pain, vitality, etc. An SF-36 score of 50 or less was considered as moderate
      to severe depression and 51-100 as mild depression to good health. 56.81% of the
      patients who are below poverty line under dialysis had moderate to severe
      depression with regard to their health status. A physical health score of up to
      50 was seen in 63.63% of patients below poverty line 63.63% (P= 0.16). A mental
      health score of 0-50 was observed in 61.63% of the cohort studied (P = 0.22).
      Among the patient with diabetes (28.33%) 55.56% had depression. Dialysis duration
      was directly associated with deteriorating physical health status and inversely
      proportional to their mental health status (P<0.05). There are problems in other
      regular activities due to depressed physical and mental health. The factors that
      were identified in this study that influence depression such as poverty status,
      increasing age, vintage and frequency of dialysis and treatment with
      erythropoietin dosage should be addressed and treated accordingly to improve the
      quality of life. Improving self-esteem with fruitful employment opportunities,
      concerted rehabilitation by professionals and easing of economic burden by
      private-public partnership is an achievable goal.

PMID- 23162268
TI  - Glomerular diseases in the Military Hospital of Morocco: Review of a single
      centre renal biopsy database on adults.
AB  - Epidemiological studies provide useful information for clinical practice and
      investigations. This report aimed to determine glomerular diseases frequencies in
      a region of Morocco. All native renal biopsies (January 2000 to December 2007) on
      adults were reviewed, but only glomerular diseases were analyzed. The diagnosis
      of each case was based on histological, immunopathological and clinical features.
      We have performed 171 renal biopsies in 161 patients (101 males and 60 females),
      the mean age was (range) 40.4 +/-15 years (16-72). Clinical indications that lead
      to renal biopsy were: nephrotic syndrome (60.3%), renal failure of unknown
      aetiology (31.6%), asymptomatic urinary abnormalities (6.2%) and nephritic
      syndrome(1.9%). Primary glomerular diseases were reported in 84 patients (52%).
      The most common histological lesion was minimal change disease (26%). Idiopathic
      membranous glomerulopathy was the second most common lesion (23%) followed by
      membranoproliferative glomerulonephritis (17%), IgA nephropathy (12%), focal and
      segmental glomerulosclerosis (9.4%) and crescentic glomerulonephritis (6%).
      Secondary glomerular diseases were reported in 53 patients (33%). Lupus nephritis
      was the secondary glomerular disease most frequent (45%) followed by amyloidosis
      (19%), diabetic nephropathy (15%), and Good pasture's syndrome (7.6%). The most
      common complications of the procedure were pain at biopsy site in 4%, gross
      hematuria in 11.1%, perirenal hematoma in 5% and hematuria requiring nephrectomy
      in 0.6% patients. Minimal change disease was the most frequent primary
      glomerulopathy and lupus nephritis was the most frequent secondary glomerulopathy
      in our group. The reasons for these findings are unclear. This information is an
      important contribution to the understanding the prevalence of renal diseases in
      North Africa.

PMID- 23162270
TI  - Holistic health assessment tool for patients on maintenance hemodialysis.
AB  - The recent emphasis on assessment of the psychological status, availability of
      newer and better methods of interpreting the anthropometric measurements of renal
      patients on dialysis therapy prompted the authors to develop the "Holistic Health
      Assessment Tool for dialysis patients (HHAT-D)." A total of 30 subjects (25-65
      years), enrolled from dialysis centers in Mumbai were administered the HHAT-D
      tool to assess anthropometric, biochemical, functional, and psychological status
      (knowledge, needs, that coping strategies) along with dietary intake. The results
      showed that majority of the patients (73.3%) were mild to moderately
      malnourished. A highly significant negative correlation of anthropometric
      measurements (BMI, lean body mass, mid arm circumference, arm muscle area, bicep
      skin fold thickness, % usual body weight, and % standard body weight) with the
      HHAT-D scores (P<0.01) confirmed the validity of the tool in assessing the degree
      of malnutrition. The poor health status of the patients was further confirmed by
      the average (40%) to poor (36.6%) flexibility status and poor dietary nutrient
      intake. Moderate (36.6%) to high (60%) coping effectiveness was recorded in the
      patients as assessed using the "coping effectiveness inventory." A high degree of
      interitem correlation (Cronbach's coefficient alpha-test value 0.836) also proved
      the reliability of the HHAT-D tool. Thus, the HHAT-D was found to be a specific
      and reliable tool for assessment of holistic health status of patients on
      maintenance hemodialysis to improve quality of life and facilitate faster
      recovery.

PMID- 23162269
TI  - Causes of death in renal transplant recipients with functioning allograft.
AB  - The survival of transplant recipients is significantly lower than age-matched
      controls in the general population. The aim of this study was to analyze the
      trends in mortality of renal allograft recipients at our centre. We
      retrospectively analyzed data from all patients who were transplanted between
      October 1988 and June 2010 and were followed at our center. Patients were
      considered to have death with graft function (DWGF) if death was not preceded by
      return to dialysis or re-transplantation. The study included 98 renal allograft
      recipients (male : female - 7.99 : 1). The mean recipient and donor ages were
      35.06 +/- 11.84 (range: 15-69) and 41.17 +/- 10.44 (range: 22-60) years,
      respectively. Basic kidney diseases were CGN (chronic glomerulonephritis)
      (60.20%), CIN (chronic interstitial nephritis) (15.31%), DN (diabetic
      nephropathy) (8.16%), ADPKD (autosomal dominant polycystic kidney disease)
      (2.04%) and others (14.29%). They were followed up for a mean 79.91 +/- 60.05
      patient-months. Mortality occurred in 25 (25.51%) patients (male : female - 4 :
      1). Causes of death were sepsis/infection (36%), coronary artery disease (28%),
      CVA (8%), failed graft (4%), and rest unknown (24%). DWGF was 88% of total death
      and contributed to 78.57% of total graft loss. Overall patient survival at 1, 5,
      10, and 15 years were 90.8%, 80.2%, 65.6%, and 59.1%, respectively (Kaplan-Meier
      analysis). Those who died exhibited significant differences in recipient's age
      (median 40 years vs 31 years, P=0.007), pretransplantation hypertension (HTN)
      (100% vs 65.75%, P<0.001), post-transplant infection (76% vs 42.47%, P=0.005),
      coronary artery disease (28% vs 1.37%, P<0.001), and serum creatinine at last
      follow up (median 2.3mg/dL vs 1.56mg/dL, P=0.003). Cardiovascular disease, in
      addition to infection, is an important cause of death during the first 15 years
      following renal transplantation even in nondiabetic recipients. Death with
      functioning graft is of concern.

PMID- 23162271
TI  - Is early removal of prophylactic ureteric stents beneficial in live donor renal
      transplantation?
AB  - Prophylactic ureteric stenting has been shown to reduce ureteric leaks and
      collecting system obstruction following renal transplantation and is in
      widespread use. However, the optimal time for removal of ureteric stents after
      renal transplantation remains unclear. Aim of this study was to compare the
      result of early versus late removal of ureteric stents after kidney
      transplantation of the laparoscopically retrieved live related donor grafts.
      Eligible patients were live donor kidney transplant recipients with normal
      urinary tracts. All recipients underwent extravesical Lich-Gregoire
      ureteroneocystostomy over 4F/160 cm polyurethane double J stents by a uniform
      technique. They were randomized on seventh postoperative day for early removal of
      stents on postoperative day 7 (Group I), or for late removal on postoperative day
      28 (Group II). The incidence of urinary tract infections, asymptomatic
      bacteriuria, and urological complications were compared. Between 2007 and 2009,
      130 kidney transplants were performed at one centre of which 100 were enrolled
      for the study, and 50 each were randomized into the two groups. Donor and
      recipient age, sex, native renal disease, immunosupression, number of rejection
      episodes, and antirejection therapy were similar in the two groups. The
      occurrence of symptomatic urinary tract infection during the follow-up period of
      6 months was significantly less in the early stent removal group [5 out of 50
      (10%) in Group I, vs 50 out of 15 (30%) in Group II, P=0.02]. Asymptomatic
      bacteriuria was documented in 2 out of 50 (4%) in Group I and 4 out of 50 (8%) in
      Group II (P=0.3). There was no statistically significant difference in the rate
      of ureteric leak, ureteric obstruction, or hematuria in the two groups (P=1.0).
      We conclude that, in kidney transplant recipients of laparoscopically retrieved
      live donor grafts, early stent removal at the end of first week reduces the
      incidence of urinary tract infection without increasing the rate of urine leak or
      ureteric obstruction.

PMID- 23162272
TI  - Hyperuricemia beyond 1 year after kidney transplantation in pediatric patients:
      Prevalence and risk factors.
AB  - Hyperuricemia is frequent among adult renal transplant recipients; however, data
      among pediatric kidney recipients are scarce. This study is designed to estimate
      the prevalence and risk factors of late post-transplant hyperuricemia in
      pediatric recipients. A retrospective observational multicenter study on 179
      pediatric renal recipients (5-18 years) was conducted between April 2008 and
      January 2011 from five kidney transplant centers of Tehran, Iran. All recipients
      were followed up for more than 1 year (5.9 +/-3.3 years) after transplantation. A
      total of 17686 blood samples were obtained for serum uric acid (SUA). The normal
      range of SUA was defined as SUA 1.86-5.93 mg/dl for children between 2 and 15
      years in both genders; 2.40-5.70 mg/dl for girls aged >15 years; 3.40-7.0 mg/dl
      for boys aged >15 and more than 6 and 7 mg/dl in boys and girls older than 15
      years old. The median age of the children was 13 years. Male recipients were more
      popular than female (male/female 59/41%). Hyperuricemia was detected in 50.2% of
      patients. Mean SUA concentration was 5.9+/-1.7 mg/dl and mean SUA concentration
      in hyperuricemic patients was 7.7+/-1.2 mg/dl. While at multivariate logistic
      regression elevated serum creatinine concentration (P<0.001) and the time span
      after renal transplantation (P=0.02) had impact on late post-transplant
      hyperuricemia. High cyclosporine level (C0 and C2) was not risk factor for
      huperuricemia. Late post-transplant hyperuricemia was found in about half of
      pediatric renal recipients, and was associated with impaired renal allograft
      function.

PMID- 23162273
TI  - The high prevalence of chronic kidney disease-mineral bone disorders: A hospital
      based cross-sectional study.
AB  - Mineral bone disorder (MBD) is an important complication of chronic kidney
      disease (CKD). However, there are limited data on the pattern of MBD in Indian
      CKD population. The aim of this study was to describe spectrum of MBD in patients
      with CKD in our center. This was a hospital-based cross-sectional observational
      study. Patients with stage 4 and 5 CKD were included in this study. Those
      receiving calcium supplement, vitamin D or its analogues, and calcimimetic were
      excluded. Serum/plasma levels of creatinine, albumin, calcium, phosphate, total
      alkaline phosphatase (TAP), intact parathormone (iPTH), and 25-OH vitaminD (25
      vitD) were measured. Radiological survey of bones was carried out in all cases,
      and echocardiography done in selected patients. Statistical analysis was done
      using Sigmaplot 10.0 software. A total of 150 patients (114 males, 36 females)
      were included in this study. Mean age was 45.67+/-16.96 years. CKD stage 4 and 5D
      were found in 26% (n=39) and 74% (n=111) of study population, respectively. The
      most common underlying native kidney diseases in patients of CKD 4 and 5D were
      diabetic nephropathy (41.03%) and CGN (41.44%), respectively. Median (first
      quartile, third quartile) values for serum levels of corrected calcium (cCa),
      phosphate, cCaXPO4 product, TAP, plasma iPTH, and 25-vitD in stage 4 CKD were
      8.36 (7.79, 8.91) mg/dL, 4.9 (3.92, 6.4) mg/dL, 41.11 (34.01, 53.81) mg(2)/dL(2),
      97 (76.5, 184.25) IU/L, 231 (124.5, 430.75) pg/mL, and 12 (6.98, 23.55) ng/mL,
      respectively; and in stage 5D CKD were 8.36 (7.66, 8.95) mg/dL, 5.7 (4.23, 6.95)
      mg/dL, 46.5 (37.16, 54.47) mg(2)/dL(2), 180 (114.5, 276.25) IU/L, 288 (169.75,
      625.0) pg/mL, and 18.4 (10.0, 26.4) ng/mL, respectively. Prevalence of
      hypocalcemia (56.41% vs. 54.95%), hyperphosphatemia (64.10% vs. 70.27%), and
      hyperparathyroidism (84.62% vs. 88.29%) was not different between patients with
      CKD 4 and 5D. However, iPTH level outside the target range and increased TAP
      level were significantly (P<0.001) more common in CKD stage 5D. Multiple logistic
      regression analysis for hyperparathyroidism revealed significant inverse
      correlation with cCa in CKD 5D. There were no significant differences in vitamin
      D status and prevalence of valvular calcification between CKD stage 4 and 5D. X
      ray revealed renal osteodystrophy in 8 (5.33%) patients, while it was normal in
      118 (78.67%) patients. Secondary hyperparathyroidism, hyperphosphatemia,
      hypocalcemia, increased TAP, and 25-OH vitamin D deficiency and insufficiency
      were quite common in CKD 4 and 5 patients. The commonest type of MBD in CKD 4 and
      5D was secondary hyperparathyroidism.

PMID- 23162274
TI  - Acute renal failure due to bilateral ureteric necrosis following percutaneous
      chemical lumbar sympathectomy.
AB  - We report a case of acute renal failure as a result of obstructive uropathy as a
      consequence of instillation of phenol used for chemical sympathectomy in
      Beurger's disease of the lower limbs. Extensive bilateral ureteral necrosis
      occurred as a result of phenol instillation that. Such practices are still common
      among the general surgeons and such a complication has not been described before.

PMID- 23162275
TI  - Polyarteritis nodosa presenting with spontaneous perirenal hematoma.
AB  - Spontaneous perirenal hematoma following ruptured microaneurysm is an unusual but
      serious complication of polyarteritis nodosa. We describe a young male who
      presented with spontaneous perirenal hematoma and was subsequently diagnosed to
      have polyarteritis nodosa. He was managed with immunosuppressive medications with
      no recurrence of symptoms.

PMID- 23162276
TI  - Hereditary ADAMTS 13 deficiency presenting as recurrent acute kidney injury.
AB  - We report here a case of 26-year-old male who presented with history of recurrent
      acute renal failure associated with microangiopathic hemolytic anemia and
      thrombocytopenia. ADAMTS 13 deficiency due to mutation in the gene encoding for
      ADAMTS 13 was identified as the cause. After eight episodes of acute kidney
      injury (AKI), patient started developing hypertension, proteinuria, and renal
      insufficiency. Treatment with regular monthly plasma infusions prevented further
      episodes of AKI and stabilized the renal function. Hypertension and proteinuria
      are controlled with angiotensin II receptor blockers.

PMID- 23162277
TI  - Postrenal transplant laryngeal and visceral leishmaniasis - A case report and
      review of the literature.
AB  - Visceral leishmaniasis (kala-azar) is a disease caused by protozoa of genus
      Leishmania. It is currently regarded as the second most dreaded parasitic
      disease, next to malaria. There have been very few case reports of visceral
      leishmaniasis among the renal transplant recipients. We present a renal allograft
      recipient with symptoms of fever, sore throat, hoarseness of voice,
      lymphadenopathy, splenomegaly, and pancytopenia after 7 years post-transplant
      period. On investigating, he was diagnosed to have extensive visceral
      leishmaniasis with laryngeal involvement. Despite extensive PubMed literature
      search, we could not find any case report of postrenal transplant visceral and
      laryngeal leishmaniasis and to the best of our knowledge this is the first case
      report of this kind.

PMID- 23162278
TI  - Chronic tubulointerstitial nephritis in a solitary kidney of a child with Noonan
      syndrome.
AB  - Noonan syndrome is a genetic disorder with involvement of many organ systems;
      facial dysmorphism and cardiovascular defects being the common abnormalities.
      Renal involvement is uncommon and abnormalities of the genitourinary system are
      usually limited to structural anomalies and cryptorchidism. We report a case of
      Noonan syndrome with chronic tubulointerstitial nephritis in a solitary kidney.

PMID- 23162279
TI  - Contrasting approaches to end of life and palliative care in end stage kidney
      disease.
AB  - With increased numbers of the elderly, including nursing home patients, being
      accepted for end-stage kidney disease (ESKD) management, there is heightened
      interest and focus on end of life decisions, advanced care planning and
      directives, withdrawal from dialysis and palliative care in this setting. Despite
      this, care at the individual patient level can vary greatly. Here, we present two
      contrasting cases to highlight the importance of early and ongoing involvement of
      palliative care in patients with ESKD. In the first case, a high quality of life
      was preserved before the patient died with dignity, with early interdisciplinary
      palliative care involvement. In the second case there was a long protracted
      period of poor quality of life prior to death. This was associated with
      resistance to the involvement of palliative care, mainly from the family.
      Addressing end of life care issues early in the chronic kidney disease (CKD)
      trajectory and ensuring patients, their families and health care providers are
      well informed, may contribute to a better outcome for the patient and their
      family.

PMID- 23162280
TI  - Catastrophic antiphospholipid antibody syndrome in a child with thrombotic
      microangiopathy.
AB  - Thrombotic microangiopathic hemolytic anemia (TMHA) is not uncommon in clinical
      nephrology practice while antiphospholipid syndrome (APS) is uncommon. Although
      less than 1% of patients with APS develop catastrophic APS (CAPS), its potential
      lethal outcome because of thrombosis in multiple organs and subsequent multiorgan
      failure emphasizes its importance in nephrology practice. Here is a case of
      catastrophic APS in a 7-year-old girl, who presented to us with TMHA associated
      with antiphospholipid antibodies and subsequently died because of CAPS.

PMID- 23162281
TI  - Reversible dialysis-dependent renal failure due to undiagnosed renovascular
      disease.
AB  - Renovascular disease (RVD) can present with resistant hypertension, acute or
      rapidly progressive renal failure and occasionally nephrotic proteinuria.
      Revascularization plays an important role in controlling blood pressure and
      preserving renal function. It is widely believed that delay in revascularization
      would result in irreversible loss of renal function. However, we report a
      favorable outcome despite delayed revascularization in two patients of RVD- one
      presenting with recurrent flash pulmonary edema and other with progressive renal
      failure. The former's serum creatinine returned to normal despite 3 months of
      anuria and the latter became dialysis-independent despite 2 months of progressive
      decline in renal function. Both remain dialysis-free 3 years after surgery.

PMID- 23162282
TI  - Succesfully treated Curvularia lunata peritonitis in a peritoneal dialysis
      patient.

PMID- 23162283
TI  - How does KDQoL-36 questionnaire predict quality of life in Indian hemodialysis
      patients?

PMID- 23162284
TI  - Unusual association of a positive pANCA pauci-immune extracapillary
      glomerulonephritis in a lupus patient.

PMID- 23162285
TI  - Neural tube defects: A need for population-based prevention program.

PMID- 23162286
TI  - Micro mapping the frequencies of beta thalassemia and sickle cell anemia in
      India: A way forward to plan control strategies.

PMID- 23162287
TI  - Stem cells: A potential regenerative future in dentistry.
AB  - In recent years, the field of dentistry has embossed its presence by taking major
      leaps in research and further bringing it into practice. The most valuable
      ongoing research in regenerative dentistry is the study on stem cells. It was
      instituted that stem cells grow rapidly and have the potential to form
      specialized dentin, bone, and neuronal cells. These neuronal cells can be used
      for dental therapies and can provide better treatment options for patients. The
      stem cells based therapies could help in new advances in treating damaged teeth,
      inducing bone regeneration and treating neural injury as well.

PMID- 23162288
TI  - Toll-like receptors in autoimmunity with special reference to systemic lupus
      erythematosus.
AB  - The Toll-like receptor (TLR) family plays a fundamental role in host innate
      immunity by mounting a rapid and potent inflammatory response to pathogen
      infection. TLRs recognize distinct microbial components and activate
      intracellular signaling pathways that induce expression of host inflammatory
      genes. Several studies have indicated that TLRs are implicated in many
      inflammatory and immune disorders. Extensive research in the past decade to
      understand TLR-mediated mechanisms of innate immunity has enabled pharmaceutical
      companies to begin to develop novel therapeutics for the purpose of controlling
      an inflammatory disease. The roles of TLRs in the development of autoimmune
      diseases have been studied. TLR7 and TLR9 have key roles in production of
      autoantibodies and/or in development of systemic autoimmune disease. It remains
      to be determined their role in apoptosis, in the pathogenesis of RNA containing
      immune complexes, differential expression of TLRs by T regulatory cells.

PMID- 23162289
TI  - Rubinstein-Taybi syndrome: Clinical profile of 11 patients and review of
      literature.
AB  - BACKGROUND: Rubinstein-Taybi syndrome (RSTS) is a rare congenital
      neurodevelopmental disorder, characterized by postnatal growth deficiency,
      typical dysmorphic features, broad thumbs and toes, and mental retardation. Very
      few cases are reported in literature from developing countries. Diagnosis is
      often delayed due to non-familiarity with the characteristic features of this
      syndrome. AIMS: To report 11 cases of RSTS and to review the current literature.
      SETTINGS AND DESIGN: Retrospective study conducted in genetic and metabolic unit
      of a tertiary care teaching hospital in north India over a period of 31/2 years.
      MATERIALS AND METHODS: 11 patients with diagnosis of RSTS were identified, and
      their case sheets were reviewed. RESULTS: Developmental delay was presenting
      complaint in 10 patients, and seizure in 1 case. 7 patients had microcephaly
      (head circumference below -3 SD), and a prominent beaked nose was seen in 9
      patients. The intelligence quotient (IQ) varied from 22-62 in 7 patients who had
      mental retardation. The most notable features in hands were broadness,
      shortening, and flattening of the distal phalanx of thumbs or great toes.
      Additionally, we also noted webbing of neck, microphthalmia, and pachygyria (on
      MRI brain) in 1 patient each. CONCLUSIONS: The diagnosis of RSTS is primarily
      clinical and based on characteristic phenotype that is often combined with a
      variety of somatic anomalies. An early diagnosis facilitates appropriate genetic
      counseling and in planning the management.

PMID- 23162290
TI  - Prevalence and hematological profile of beta-thalassemia and sickle cell anemia
      in four communities of Surat city.
AB  - BACKGROUND: From the data of transfusion-dependent thalassemia major cases, the 4
      communities (Muslim, Dhodia Patel, Kachhiya Patel, and Modh Bania) with high
      prevalence but not studied methodically were selected. AIM: The aim of this study
      is to find prevalence of beta-thalassemia and sickle cell anemia in 4 selected
      communities and also to evaluate hematological profile in them. MATERIALS AND
      METHODS: For screening of beta-thalassemia trait (BTT) and sickle cell trait
      (SCT), all samples were tested for red cell indices, solubility, HbA(2) level and
      doubtful cases confirmed on HPLC. STATISTICAL ANALYSIS: Mean +/- SD, chi(2) and
      't' tests were used to evaluate the significance. RESULTS AND CONCLUSION: Among 4
      selected communities, the highest prevalence of BTT was observed in Modh Bania
      (6.2%) and Kachhiya Patel (6.05%) and that of SCT in Dhodia Patel (14.0%).
      Significantly higher prevalence of BTT was observed in Memon (P < 0.0001) and of
      SCT in Khalifa 6.6% (P < 0.0001) compared to other Muslim sub castes. Anemia was
      more prevalent in BTT compared to non-BTT and non-SCT subjects. 80% of Dhodia
      Patel non-BTT and non-SCT subjects showed microcytic red cell morphology. Their
      Mean +/- SD Hb concentration was 12.1 +/- 1.73, hence iron deficiency cannot be a
      sole reason. This community needs alpha-thalassemia and iron studies.

PMID- 23162291
TI  - Association of microsatellite instability and chronic obstructive pulmonary
      disorder in isocyanate-Exposed population of Bhopal.
AB  - CONTEXT: Survivors of the Bhopal gas disaster still suffer from various
      respiratory ailments. We examined the effects of exposures among a cross-section
      of current residents suffering from COPD by ISSR-PCR. AIMS: Molecular screening
      of the gas-affected population of Bhopal with COPD for microsatellite instability
      due to exposure of MIC. SETTINGS AND DESIGN: The isocyanate-exposed population of
      Bhopal city suffering from chronic obstructive pulmonary disorder. MATERIALS AND
      METHODS: Inter-(SSR) analysis was used to characterize microsatellite instability
      in 52 MIC victims of Bhopal, suffering from COPD using (CA)(8)RG and (CA)(8)R[Y
      Q] primer. STATISTICAL ANALYSIS USED: Association analyses were performed using
      regression analysis. RESULTS: The study on the MIC-affected population in Bhopal
      showed weak association between microsatellite instability and age (r = + 0.37);
      exposure distance from site (r = -0.44); and smoking status(r = + 0.12); while
      regression analysis of the above parameters displayed supporting evidence.
      CONCLUSIONS: The high prevalence of smoking coupled with aging and poor living
      habits threatens, to further increase COPD incidences among this population,
      highlighting the need for enhanced screening efforts.

PMID- 23162292
TI  - Effect of maternal Tp53 gene G412C polymorphism on neural tube defects: A study
      from North India.
AB  - CONTEXT: Tumor protein 53 (tp53) is one of the candidate gene proposed for neural
      tube defects, which affects central nervous system during early embryonic
      development, on the basis of mouse models. AIMS: The present study is an attempt
      to unfold the possible role of tp53 G412C polymorphism in the incidence of neural
      tube defect (NTDs) in humans. SETTINGS AND DESIGN: Case-control study was carried
      out in government hospitals of Delhi, India. MATERIALS AND METHODS: Subjects
      comprised of 100 mothers of NTD children and 100 matched control mothers.
      Information on some environmental exposures was collected along with blood
      samples. After DNA extraction, the genotyping of tp53 G412C polymorphism was
      carried out by PCR-RFLP method.  STATISTICAL ANALYSYS: Fisher Exact or Chi square
      test, binary logistic model, and odds ratio (95% confidence interval)
      calculations were used to evaluate effect of risk factors on NTDs using SPSS
      v17.0. RESULTS: The 'CC' genotype of tp53 G412C showed protective effect towards
      the development of anencephaly and/or encephalocele (OR: 0.44; 95% CI: 0.19
      1.00); however, no significant difference among overall NTD cases and controls
      was observed (P>0.05). Further segregation of all subjects based on 2 different
      communities, Hindus and Muslims, the association of 'CC' genotype of the
      polymorphism with reduced NTD risk was observed among Hindu community (OR: 0.33;
      95% CI: 0.13-0.79). CONCLUSION: The study highlights the selective advantage
      provided by maternal 'CC' genotype, thereby reducing risk of cephalic NTDs,
      probably due to the lower apoptotic activity of the protein, however, more
      specifically in the presence of community-specific microenvironment.

PMID- 23162293
TI  - Chromosomal abnormalities and hormonal disorders of primary amenorrhea patients
      in Egypt.
AB  - BACKGROUND: Primary amenorrhea is defined as the absence of menstruation and
      secondary sexual characteristics in phenotypic women aged 14 years or older.
      Hormonal disorders are main causes of primary amenorrhea. Common hormonal cause
      of primary amenorrhea includes pituitary dysfunction and absent ovarian function.
      The aim of this study was to estimate the incidence and types of chromosomal
      abnormalities in patients with primary amenorrhea in Egypt. MATERIALS AND
      METHODS: Chromosomal analysis and hormonal assay were carried out on 223 patients
      with primary amenorrhea that were referred from different parts of Egypt to
      Cytogenetic laboratory of Genetic Unit, Children Hospital Mansoura University,
      from July 2008 to December 2010. FISH technique was carried out in some of cases
      to more evaluation. RESULTS: The frequency of chromosomal abnormalities was 46
      (20.63%) in primary amenorrhea patients. The chromosomal abnormalities can be
      classified into four main types. (1) The numerical abnormalities of the X
      chromosome were detected in 23 (50 %). (2) Structural abnormalities of the X
      chromosome were detected in 11 (23.91%). (3) Mosaicism of X chromosome was found
      in 10 (21.74%). (4) Male karyotype 46, XY was presented in 2 (4.35%). CONCLUSION:
      The present study showed that karyotype and FISH are necessary to detect the
      causes of primary amenorrhea. This study also revealed the incidence of
      chromosomal abnormalities in women with primary amenorrhea in Egypt is similar to
      that reported in previous literatures.

PMID- 23162294
TI  - Genetic and environmental determinants of menstrual characteristics.
AB  - BACKGROUND: The impact of women's menstrual cycle on her quality of life, health,
      work, and community is substantial. Menstrual disturbance is linked with general
      ill conditions such as migraine, asthma, and endocrinopathies. The clinical
      significance of medical interventions to prevent these conditions becomes clear
      if the role of genetic or environment is clarified. AIMS: To identify the genetic
      and environmental contribution on menstrual characteristics. SETTING AND DESIGN:
      This was a cross-sectional study in 2 Asian countries. MATERIALS AND METHODS: 2
      cohorts of monozygotic and dizygotic twins born between (1945-1988, n = 122) and
      (1951-1993, n = 71) were taken. A standard questionnaire was designed inclusive
      of socio- demographic characteristics of subjects as well as menstrual history
      (duration, interval, amount, irregularity). Subjects were interviewed by phone.
      STATISTICAL ANALYSIS: Quantitative variables were analyzed using Falconars'
      formula as well as maximum likelihood analysis. Structural modeling was then
      applied to twin correlations to provide estimates of the relative genetic and/or
      environmental factors contribution in determining the measured trait. RESULTS:
      Menstrual characteristics were found to be under environmental influence where
      the best fitting model for menstrual interval and duration was common
      environment. CDF plotting confirmed the results for both variables. Proband-wise
      concordance analysis for amount of menstruation, amenorrhea, and irregular
      menstruation revealed no genetic influence. The best fitting model for menstrual
      irregularity was CE (C73%, E27%). The same model was defined for amenorrhea
      (C48%, E52%). CONCLUSIONS: Environmental factors are most likely responsible to
      determine the menstrual flow, its integrity, and regularity. These factors need
      to be studied further.

PMID- 23162295
TI  - Molecular epidemiology of beta-thalassemia in Pakistan: Far reaching
      implications.
AB  - BACKGROUND: beta -Thalassaemia, an autosomal recessive hemoglobinopathy, is one
      of the commonest genetically transmitted disorders throughout the world.
      Collective measures including carrier identification, genetic counseling and
      prenatal diagnosis are required for preventing beta-thalassemia. AIM: To achieve
      this objective, Identification of the spectrum of genetic mutations, especially
      for various ethnic backgrounds in Pakistan. Therefore, we designed a cross
      sectional prospective study to identify the frequency of various gene mutations
      in different ethnic groups of Pakistan. MATERIALS AND METHODS: Over a 5-year
      period, DNA from 648 blood samples {including specimens of chorionic villus
      sampling (CVS)} were analyzed for the twelve most common beta-thalassemia
      mutations found in the Pakistani population by a Multiplex amplification
      refractory mutation system (ARMS). Each sample was analyzed for the mutation as
      well as the normal gene, appropriate with negative and positive controls, and
      reagent blanks. RESULTS: Out of 648 samples mutations were identified in 640
      (98.75%) samples by multiplex ARMS. 8 common beta-thalassemia mutations were
      identified in 8 different ethnic groups accounting for 93.9% of the beta
      thalasemia alleles. CONCLUSIONS: Based on the outcome of this study a cost
      effective proposal is formulated for detection of beta-thalassemia mutations.

PMID- 23162296
TI  - Cytogenetic abnormalities in 222 infertile men with azoospermia and oligospermia
      in Iran: Report and review.
AB  - BACKGROUND: Infertility affects approximately 10%-15% of couples in reproductive
      age. In half of the couples, causes are male-related, associated with impaired
      spermatogenesis. There is a complex correlation between genetics and infertility.
      Several factors affect on gametogenesis, from which factors that lead to
      chromosomal abnormalities are one of the best known. The aim of this study was to
      determine type and rate of chromosomal abnormalities in infertile azoospermic and
      oligospermic males in Iranian population. MATERIALS AND METHODS: The records of a
      total of 222 participants were evaluated retrospectively. RESULTS: As a whole we
      observed 13.96% chromosomal abnormality, from which 12.15% showed numerical and
      1.8% showed structural abnormalities. CONCLUSION: Comparison of our results with
      the review of the literature shows a higher incidence (4- fold) of gonosomal, in
      particular, numerical gonosomal, chromosomal anomalies. Cytogenetic analysis is
      strongly suggested for infertile men, particularly in those who suffer from
      azoospermia.

PMID- 23162297
TI  - Discerning non-disjunction in Down syndrome patients by means of GluK1-(AGAT)(n)
      and D21S2055-(GATA)(n) microsatellites on chromosome 21.
AB  - INTRODUCTION: Down syndrome (DS), the leading genetic cause of mental
      retardation, stems from non-disjunction of chromosome 21. AIM: Our aim was to
      discern non-disjunction in DS patients by genotyping GluK1-(AGAT)(n) and D21S2055
      (GATA)(n) microsatellites on chromosome 21 using a family-based study design.
      MATERIALS AND METHODS: We have used a PCR and automated DNA sequencing followed
      by appropriate statistical analysis of genotype data for the present study
      RESULTS AND DISCUSSION: We show that a high power of discrimination and a low
      probability of matching indicate that both markers may be used to distinguish
      between two unrelated individuals. That the D21S2055-(GATA)(n) allele
      distribution is evenly balanced, is indicated by a high power of exclusion
      [PE=0.280]. The estimated values of observed heterozygosity and polymorphism
      information content reveal that relative to GluK1-(AGAT)(n)[H(obs)=0.286], the
      D21S2055- (GATA)(n)[H(obs)=0.791] marker, is more informative. Though allele
      frequencies for both polymorphisms do not conform to Hardy-Weinberg equilibrium
      proportions, we were able to discern the parental origin of non-disjunction and
      also garnered evidence for triallelic (1:1:1) inheritance. The estimated
      proportion of meiosis-I to meiosis-II errors is 2:1 in maternal and 4:1 in
      paternal cases for GluK1-(AGAT)(n), whereas for D21S2055-(GATA)(n), the ratio is
      2:1 in both maternal and paternal cases. Results underscore a need to
      systematically evaluate additional chromosome 21-specific markers in the context
      of non-disjunction DS.

PMID- 23162298
TI  - The study of gene GJB2/DFNB1 causing deafness in humans by linkage analysis from
      district Peshawar.
AB  - Families with at least 2 or more individuals having hereditary hearing loss were
      enrolled from different areas of Khyber Pakhtoonkhwa, mainly from district
      Peshawar. Detailed history was taken from each family to minimize the presence of
      other abnormalities and environmental causes for deafness. Families were
      questioned about skin pigmentation, hair pigmentation, and problems relating to
      balance, vision, night blindness, thyroid, kidneys, heart, and infectious
      diseases like meningitis, antibiotic usage, injury, and typhoid. The pedigree
      structures were based upon interviews with multiple family members, and pedigrees
      of the enrolled families were drawn using Cyrillic program (version 2.1). All
      families showed recessive mode of inheritance. I studied 8 families of these 10.
      For linkage analyses, studies for DFNB1 locus, 3 STR markers (D13S175, D13S292,
      and D13S787) were genotyped using polyacrylamide gel electrophoresis (PAGE) and
      haplotypes were constructed to determined, linkage with DFNB1 locus. From a total
      of 8 families, a single family-10 showed linkage to DFNB1 locus.

PMID- 23162299
TI  - Lack of association between the G-660C polymorphism in the dopamine transporter
      gene (SLC6A3) and schizophrenia in the Iranian population.
AB  - BACKGROUND: Dopaminergenic system plays an essential role in the plasticity of
      the human brain. The dopamine transporter gene (SLC6A3) mediates active reuptake
      of dopamine from synapsis, terminates dopamine signals, and therefore, is
      implicated in a number of dopamine-related disorders like psychosis. Variations
      in the form of single nucleotide polymorphisms in the core promoter of the SLC6A3
      gene are reported to be involved in the pathogenesis of schizophrenia. In this
      study, we also attempted to establish the possible role of the polymorphism G
      660C in the SLC6A3 gene promoter in schizophrenia in a case-control study.
      MATERIALS AND METHODS: The allele and genotype frequency were analyzed in an
      Iranian cohort of 200 unrelated patients and 200 controls using polymerase chain
      reaction and restriction fragment length polymorphism. RESULTS: The genotype
      frequency for case and control groups was GG 100%, GC 0%, CC 0%, and GG 100%, GC
      0%, CC 0%, respectively. The C allele was failed in both groups. CONCLUSION: Our
      data suggest clearly that there is no association between the -660G/C
      polymorphism and outcome of schizophrenia in the Iranian population.

PMID- 23162300
TI  - Adjusted classification for ultrasound scoring index for antenatal detection of
      fetal trisomy.
AB  - Ultrasound (USG) is a useful investigation in obstetrics. Its mean indications
      include screening for fetal anomaly, especially for Down's syndrome and other
      genetic trisomy. Here, the author tries to access the compatibility between
      classical USG scoring index and the new likelihood ratio-based system. New
      recommendation on severity of studied markers is given.

PMID- 23162301
TI  - An investigation of Ph(1) chromosome in Chronic Myeloid Leukemia patients with
      different treatment modalities and hematological features.
AB  - Chronic myeloid leukemia (CML) is characterized by a Ph(1) chromosome that
      derives through a translocation between chromosomes 9 and 22, i.e., t (9;22).
      Identifying the Ph(1) chromosome through cytogenetic analysis is an important
      aspect of CML diagnosis. The aim of this study was to determine the significance
      of cytogenetic analysis in the diagnosis of CML as well as to find out a
      relationship between chromosomal abnormalities and CML patients in different
      stages of treatment. Six CML patients were investigated for this study. The
      presence of Ph(1) chromosome was detected at different times of treatment using
      GTG banding on peripheral blood or bone marrow aspirations, and the results were
      analyzed using cytovision workstation. Hematological features were compared
      between newly diagnosed patients and patients under treatment. The Ph(1)
      chromosome was strongly associated with all cases of CML. The regression of Ph(1)
      chromosomes differed for each patient depending on the treatments and individual
      response to specific treatments.

PMID- 23162302
TI  - Crigler-Najjar syndrome type 2: Novel UGT1A1 mutation.
AB  - Crigler-Najjar syndrome type 2 is a rare cause for persistent unconjugated
      hyperbilirubinemia, inherited in an autosomal recessive manner. Even though it is
      compatible with normal life span, in the absence of prompt suspicion and
      intensive management it can prove fatal not only in the neonatal period but also
      during adult life. Here, we describe a case with a novel homozygous UGT1A1
      p.Pro176Leu mutation.

PMID- 23162303
TI  - Smith-Lemli-Opitz-syndrome.
AB  - Smith-Lemli-Opitz syndrome is an autosomal recessively inherited disorder. A
      severe defect in cholesterol biosynthesis has been identified leading to
      abnormally low plasma cholesterol levels and elevated levels of the cholesterol
      precursor 7-dehydrocholesterol, the result of deficiency of 7-dehydrocholesterol
      reductase. We describe one such child with Smith-Lemli-Opitz syndrome. This child
      had clinical features similar to Smith-Lemli-Opitz syndrome like facial
      dysmorphism and cardiac and renal anomalies with failure to thrive.

PMID- 23162304
TI  - A familial deletion 4q syndrome: An outcome of a paracentric inversion.
AB  - Chromosome inversions are intra-chromosomal rearrangements formed when the
      chromosome breaks occur at two places, and in the process of repair the
      intervening segments are joined in an inverted or opposite manner. Inversions
      themselves do not appear to cause clinical anomalies, if balanced. Abnormal
      phenotypes can occur due to gene disruption at the point of breakage and reunion
      or due to duplication/deficiency recombinants formed during crossover at meiosis.
      We report a case with familial deletion 4q syndrome in a 1-year-old female child
      with dysmorphism and congenital abnormalities. The deletion was an outcome of a
      paracentric inversion 4q31.2q35.2. The deletion was confirmed by fluorescence in
      situ hybridization using telomeric DNA probes for chromosome No. 4. An attempt
      was made to correlate the genotype with the phenotype. The father had the same
      rearrangement with a milder phenotype. The recurrence risk in such cases is high.

PMID- 23162305
TI  - 46,XX, der(15),t(Y;15)(q12;p11) karyotype in an azoospermic male.
AB  - We report on a Yq/15p translocation in a 23-year-old infertile male referred for
      Klinefelter Syndrome testing, who had azoospermia and bilateral small testes.
      Hormonal studies revealed hypergonadotropic hypogonadism. Conventional
      cytogenetic procedures giemsa trypsin giemsa (GTG) and high resolution banding
      (HRB) and molecular cytogenetic techniques Fluorescence In Situ Hybridization
      (FISH) performed on high-resolution lymphocyte chromosomes revealed the karyotype
      46,XX, t(Y;15)(q12;p11). SRY-gene was confirmed to be present by classical
      Polymerase Chain Reaction (PCR) methods. His father carried de novo derivative
      chromosome 15 [45,X, t(Y;15)(q12;p11)] and was fertile; the karyotype of the
      father using G-band technique confirmed a reciprocal balanced translocation
      between chromosome Y and 15. In the proband, the der (15) has been inherited from
      the father because the mother had a normal karyotype (46,XX). In the proband, the
      der (15) could have produced genetic imbalance leading to unbalanced robertson
      translocation between chromosome Y and 15, which might have resulted in
      azoospermia and infertility in the proband. The paternal translocation might have
      lead to formation of imbalanced ova, which might be resulted infertility in the
      proband. Sister's karyotypes was normal (46,XX) while his brother was not
      analyzed.

PMID- 23162306
TI  - Mosaic triple X syndrome in a female with primary amenorrhea.
AB  - BACKGROUND: Turner's syndrome is the most common chromosomal abnormality in
      females, affecting 1 in 2,500 live female births. It is a result of absence of an
      X chromosome or the presence of a structurally abnormal X chromosome. Its most
      consistent clinical features are short stature and ovarian failure. AIM: The aim
      of the study was to report a rare case of mosaic triple X syndrome in a female
      with primary amenorrhea. MATERIALS AND METHODS: The chromosomal analysis using
      GTG banding was carried out, which revealed a mosaicism with 45,XO/47,XXX
      chromosomal constitution. Fluorescent in situ hybridization was also carried out
      to further confirm the observation made in the study. CONCLUSION: The physical
      features presented by the female could be due to the 45,XO/47,XXX mosaicism and
      the karyotype analysis was consistent with the diagnosis and clinical symptoms.
      Triple X mosaicism was confirmed with conventional and molecular cytogenetic
      analysis.

PMID- 23162307
TI  - Genetic counseling in carriers of reciprocal translocations involving two
      autosomes.
AB  - One of the main genetic causes involve in the pathogenesis of recurrent abortion
      is parental chromosomal abnormalities. The central concept in genetic counseling
      with such families is to estimate the probability of recurrence of unfavorable
      pregnancy outcomes. The main questions that consultants usually ask are: Why did
      this happen? What is the risk to be done again?Our cases were two families with
      repeated miscarriage. The pedigrees were drawn, the chromosomes of couples were
      studied, and estimation for recurrent risk was done. We tried to answer those two
      main questions and clear the results for them.Parental chromosome abnormalities
      were founded after karyotyping with GTG technique at 450 band resolution,
      revealing 46 chromosomes with balanced translocation of autosomes in one of the
      partner in both families. Recurrent risk was estimated as "high" for their future
      pregnancies in each family.Couples in which one partner is the carrier of such
      balanced translocation have increased risks of infertility, recurrent abortion,
      and delivery of chromosomally abnormal offspring. Genetic counseling of such
      couples, therefore, presents a unique challenge and should be considered in
      dealing with such families.

PMID- 23162308
TI  - Waardenburg syndrome: A rare genetic disorder, a report of two cases.
AB  - Waardenburg syndrome (WS) is a rare genetic disorder. Patients have heterochromia
      or eyes with iris of different color, increased inter-canthal distance, distopia
      canthorum, pigmentation anomalies, and varying degree of deafness. It usually
      follows autosomal dominant pattern. In this report, two cases have been discussed
      but no familial history of WS has been found. Counseling of the patient is
      necessary and cases of irreversible deafness have been treated.

PMID- 23162309
TI  - Unusual manifestation of Marden-Walker syndrome.
AB  - Marden-Walker syndrome (MWS) is characterized by multiple joint contractures, a
      mask-like face with blepharophimosis, micrognathia, high-arched or cleft palate,
      low-set ears, decreased muscular bulk, arachnodactyly, and kyphoscoliosis. We
      report a case of MWS along with unusual manifestation of neurological,
      cardiovascular, and genitourinary system.

PMID- 23162310
TI  - Association of generalized aggressive periodontitis and ectrodactyly-ectodermal
      dysplasia-cleft syndrome.
AB  - Ectrodactyly-ectodermal dysplasia-cleft (EEC) syndrome is an autosomal dominant
      disorder characterized by the triad of ectrodactyly, ectodermal dysplasia, and
      facial clefting. Even though literature has documented the association of various
      genetic disorders with aggressive periodontitis, the periodontal manifestations
      in patients with EEC syndrome have never been addressed. This case report
      presents the periodontal status of three patients in a family with EEC syndrome.
      The presence of generalized aggressive periodontitis was noticed in these
      patients. EEC syndrome could be a new addition to the group of genetic disorders
      associated with aggressive periodontitis.

PMID- 23162311
TI  - A case of Kartagener's syndrome: Importance of early diagnosis and treatment.
AB  - Kartagener's syndrome is a very rare congenital malformation comprising of a
      classic triad of sinusitis, situs inversus and bronchiectasis. Primary ciliary
      dyskinesia is a genetic disorder with manifestations present from early life and
      this distinguishes it from acquired mucociliary disorders. Approximately one half
      of patients with primary ciliary dyskinesia have situs inversus and, thus are
      having Kartagener syndrome. We present a case of 12 year old boy with sinusitis,
      situs inversus and bronchiectasis. The correct diagnosis of this rare congenital
      autosomal recessive disorder in early life is important in the overall prognosis
      of the syndrome, as many of the complications can be prevented if timely
      management is instituted, as was done in this in this case.

PMID- 23162312
TI  - An unusual clonal cytogenetic abnormality with t(15;17)(p11;q21) in a patient
      with severe aplastic anemia.

PMID- 23162313
TI  - Honey, chromosomal breakage and fanconi anemia.

PMID- 23162314
TI  - Large scale Meta-analysis of genetic studies in ischemic stroke: Five genes
      involving 152,297 individuals.

PMID- 23162315
TI  - Things do not change, We change! - David Henry Thoreau.

PMID- 23162316
TI  - Not why! Why not?

PMID- 23162317
TI  - From the desk of Dr. (Brigadier) JK Gupta VSM (Retd), Veteran Periodontist.

PMID- 23162318
TI  - Response to "Gingival squamous cell carcinoma: A diagnostic impediment".

PMID- 23162319
TI  - Authors' reply.

PMID- 23162320
TI  - Short implants: A systematic review.
AB  - BACKGROUND: Short implants are manufactured for use in atrophic regions of the
      jaws. Although many studies report on short implants as <=10 mm length with
      considerable success, the literature regarding survival rate of <=7 mm is sparse.
      PURPOSE: The purpose of this study was to systematically evaluate the
      publications concerning short dental implants defined as an implant with a length
      of <=7 mm placed in the maxilla or in the mandible. MATERIALS AND METHODS: A
      Medline and manual search was conducted to identify studies concerning short
      dental implants of length <=7 mm published between 1991 and 2011. The articles
      included in this study report data on implant length <=7 mm, such as demographic
      variables, implant type, location in jaws, observation time, prostheses and
      complications. RESULTS: The 28 included studies represent one randomized
      controlled trial, 12 prospective studies and 10 retrospective studies. The
      survival rate of short implant was found to be increased from 80% to 90%
      gradually, with recent articles showing 100%. CONCLUSION: When severe atrophy of
      jaws was encountered, short and wide implants can be placed successfully.

PMID- 23162321
TI  - Role of green tea as an antioxidant in periodontal disease: The Asian paradox.
AB  - Green tea is a popular beverage nowadays and intake of green tea polyphenols has
      shown preventive effect against cancer and cardiovascular disease in experimental
      and epidemiologic studies. Several studies have suggested that green tea
      catechins, such as epigallocatechin gallate, inhibit periodontal pathogens and
      reduce the destruction of periodontal tissue. This paper aims to review the role
      of green tea in inflammatory diseases, especially in periodontal diseases.

PMID- 23162322
TI  - Role of antibiotics in generalized aggressive periodontitis: A review of clinical
      trials in humans.
AB  - BACKGROUND: It is well-recognized fact that periodontal diseases are caused by
      multifactorial etiologies, in which microorganisms play an important role. An
      essential component of therapy is to eliminate or manage these pathogens. This
      has been traditionally accomplished through mechanical means by scaling and root
      planning which is ineffective in some of the aggressive periodontal diseases.
      These aggressive diseases involve particular groups of microorganisms which are
      not eliminated by mechanical means; and they require anti-infective therapy,
      which includes local and systemic antimicrobials. This approach of therapy is of
      interest to periodontist due to the aforementioned shortcomings of conventional
      methods. MATERIALS AND METHODS: A manual and electronic search was made for human
      studies up to March 2011 that presented clinical and microbiological data for the
      efficacy of a systemic antibiotics in generalized aggressive periodontitis along
      with scaling and root planning. A systematic approach was followed by two
      independent reviewers and included eligibility criteria for study inclusion,
      quality assessment, and determination of outcome measures, data extraction, data
      synthesis, and drawing of conclusion. RESULTS: Only three randomized controlled
      human trials qualified, and they concluded that both scaling and root planing
      (SRP) mono-therapy and SRP with antibiotics proves beneficial in improving
      clinical and microbiological parameters in aggressive periodontitis. Better
      results were seen in SRP with antibiotic groups as compared with SRP alone.
      CONCLUSION: Because of the insufficient quantity and heterogenecity of studies,
      no adequate evidence could be gathered to use the beneficial effects of these
      antibiotics along with SRP in aggressive periodontitis compared with SRP alone.

PMID- 23162323
TI  - Risk assessment for periodontal disease.
AB  - The prevention and treatment of periodontal disease is based on accurate
      diagnosis, reduction or elimination of causative agents, risk management and
      correction of the harmful effects of the disease. The practice of risk assessment
      involves dental care providers identifying patients and populations at increased
      risk of developing periodontal disease. This can have a significant impact on
      clinical decision making. Risk assessment reduces the need for complex
      periodontal therapy, improve patient outcome and, ultimately, reduce oral health
      care cost. The awareness of risk factors also helps with the identification and
      treatment of co-morbidities in the general population as many periodontal disease
      risk factors are common to other chronic diseases such as diabetes,
      cardiovascular diseases and stroke.

PMID- 23162324
TI  - Scanning electron microscopy study to analyze the morphological characteristics
      of root surfaces after application of Carisolv gel in association with scaling
      and root planing: In vitro study.
AB  - CONTEXT: There has been considerable interest in the use of chemical-assisted
      root detoxification. Chemical agents have been proposed to facilitate calculus
      removal. AIMS: A study was carried out to analyze the morphological
      characteristics of the root surfaces after application of Carisolv gel in
      association with scaling and root planing under scanning electron microscopy
      (SEM). SETTINGS AND DESIGN: The Department of Periodontics of the K. M. Shah
      Dental College and Hospital, Vadodara, (Gujarat, India). MATERIALS AND METHODS:
      SIXTY PERIODONTALLY COMPROMISED EXTRACTED HUMAN TEETH WERE RANDOMLY ASSIGNED TO
      FOUR GROUPS: (1) scaling and root planning (SRP) alone; (2) passive topical
      application of Carisolv + SRP; (3) active topical application of Carisolv + SRP;
      (4) multiple applications of Carisolv + SRP. Carisolv gel was applied to the root
      surfaces for 30 seconds, followed by scaling and root planing, consisting of 30
      strokes, with Gracey curettes in an apical-coronal direction, parallel to the
      long axis of the tooth. The only exception was group 4, where the roots were
      instrumented until a smooth, hard, and glass-like surface was achieved. All
      specimens were further analyzed by SEM. STATISTICAL ANALYSIS: The Analysis of
      Variance (ANOVA) method was used. RESULTS: Active application of Carisolv gel
      produced more extensive morphological changes than passive application and SRP
      alone. When multiple applications of Carisolv with SRP were performed, there was
      a significant decrease in the smear layer compared to a single application of the
      gel, either passively or actively. CONCLUSIONS: The Carisolv gel failed to remove
      the smear layer completely, especially with a single application, independently
      of the method of application. This study documented that the Carisolv gel
      produced changes in the root morphology of periodontally compromised teeth, only
      when it was applied actively and multiple times.

PMID- 23162325
TI  - Comparison of fibrin clot adhesion to dentine conditioned with citric acid,
      tetracycline, and ethylene diamine tetra acetic acid: An in vitro scanning
      electron microscopic study.
AB  - AIM: The purpose of this study was to evaluate and compare the root surface
      changes subsequent to the application of citric acid, tetracycline,
      Ethylenediaminetetraacetic acid (EDTA), and the combination of citric acid and
      tetracycline, and its influence on the adhesion of a fibrin clot with and without
      mild disruptive forces. MATERIALS AND METHODS: A total of 100 periodontally
      diseased root specimens were grouped into Saline (control Group I), 24% EDTA gel
      (Group-II), Citric acid (Group-III), Tetracycline (Group IV), and Citric acid +
      tetracycline (Group V) treatment groups containing 20 in each. After root
      conditioning, fresh human blood was applied to each root specimen and was allowed
      to clot. Ten specimens in each group were rinsed in phosphate-buffered saline and
      designated as 'Non-agitated'. The remaining ten specimens from each group were
      rinsed in phosphate-buffered saline on a rotary shaker and designated as
      'Agitated'. The roots were processed for scanning electron microscopy (SEM) to
      assess and compare the clot adhesion on them. The scores were compared through
      standard statistical packages. RESULTS: The highest mean blood clot adhesion
      score was observed in roots treated with a combination of citric acid and
      tetracycline, whereas, the least score was observed in roots treated with saline.
      CONCLUSION: The root specimens treated with the combination of citric acid and
      tetracycline as well as citric acid alone, best supported the fibrin clot.
      Tetracycline alone appeared to be less effective in supporting the clot. EDTA gel
      of 24% was least effective to promote the adhesion of a fibrin clot.

PMID- 23162326
TI  - Comparative evaluation of effects of chlorhexidine and tetracycline on neutrophil
      viability and functions in vitro.
AB  - BACKGROUND: Chlorhexidine (CHX) and Tetracycline (TET) are the two antimicrobial
      agents used in the management of periodontal infections, due to their
      antimicrobial potency and substantivity. The benefits and limitations of an
      antimicrobial agent can only be assessed by determining their relative toxicity
      to microbes and host cells. OBJECTIVES: (1) To detect the effects of CHX and TET
      on neutrophil viability and functions in vitro. (2) To compare the effects of CHX
      and TET on crevicular blood neutrophils. MATERIALS AND METHODS: Crevicular blood
      was collected using 5-MUl pipette, stored in EDTA-containing vacutainers and sent
      for evaluation of Cell Viability- Neutrophils would be mixed with 0.25 volume of
      0.4% trypan blue in Hank's balanced salt solution (HBSS) and counted to assess
      the viability. Chemotaxis- Evaluated under agarose slides, a total of 100 MUl
      crevicular blood Neutrophils-0.2% BSA or HBSS-0.2% containing concentration of
      CHX and TET. Oxidative Metabolism- would be assessed using nitro blue
      tetrazolium. In all experiments, three concentrations of TET (0.1%, 0.05%,
      0.025%) and CHX (0.01%, 0.005%, 0.0025%) respectively were used. N-Formyl
      methionyl leucyl phenylalanine (1 MUm) in the presence of 2 MUg/ml cytochalasin B
      will be used as the activating agent. Neutrophils would be treated with CHX and
      TET similarly to that for chemotaxis. RESULTS: TET comparatively has less
      deleterious effects on neutrophil functions as compared with that of CHX with
      statistically significant results for all parameters tested. CONCLUSION: From
      this study, it is inferred that CHX and TET do cause certain changes in
      neutrophil functions.

PMID- 23162327
TI  - Effect of smoking on salivary composition and periodontal status.
AB  - BACKGROUND: The purpose of this study was to evaluate and compare the effect of
      smoking on the periodontal status and salivary composition of whole saliva in
      subjects with clinically healthy periodontium and chronic periodontitis.
      MATERIALS AND METHODS: The study comprised of 400 subjects equally divided into
      four groups of non-smokers with clinically healthy periodontium, smokers with
      clinically healthy periodontium, non-smokers with chronic periodontitis and
      smokers with chronic periodontitis. Clinical measurements and non-stimulated
      whole saliva were obtained. Biochemical analysis of salivary total protein,
      calcium, magnesium and phosphorus was performed. RESULTS: The clinical parameters
      of probing depth and clinical attachment levels did not reveal any statistically
      significant differences between the smokers and non-smokers groups. The plaque
      index and gingival index were significantly higher in smokers with periodontitis
      (P<0.05) as compared with non-smokers with periodontitis. On biochemical analysis
      of whole saliva, total protein, calcium, magnesium and phosphorus were reduced in
      smokers with periodontitis to 0.43+/-0.50 gm/dL, 3.47+/-1.49 mg/dL, 0.80+/-3.87
      mEq/L Neo and 18.45+/-8.77 mg% from 1.70+/-2.09 gm/dL, 13.89+/-10.34 mg/dL,
      1.26+/-0.90 mEq/L Neo and 29.23+/-16.02 mg%, respectively, in non-smokers with
      healthy periodontium. CONCLUSION: The present study exhibited reduced
      concentrations of total proteins, calcium, magnesium and phosphorus in whole
      saliva in smokers with chronic periodontitis. It may thus be concluded that the
      analysis of salivary composition could be used as an auxiliary means of
      diagnosis.

PMID- 23162328
TI  - Estimation and comparison of osteopontin levels in plasma in subjects with
      healthy periodontium and generalized chronic periodontitis and its assessment
      after scaling and root planing.
AB  - BACKGROUND: Osteopontin (OPN) is a bone matrix derivative, whose levels reflect
      active lesions of aggravated periodontal disease accompanied by alveolar bone
      resorption. OPN is also a component of human atherosclerotic plaque, suggesting a
      role of OPN in cardiovascular diseases. The present study was conducted to assess
      and compare plasma OPN levels in subjects with healthy periodontium and
      generalized chronic periodontitis and to evaluate the effect of scaling and root
      planing on Plasma OPN levels of generalized chronic periodontitis subjects.
      MATERIALS AND METHODS: 40 gender matched subjects were divided into two equal
      groups, Group I- Healthy and Group II- Generalized chronic periodontitis, based
      on the Periodontal Disease Index. Blood samples were collected from the subjects
      at the time of clinical examination (Group I, II) and two months after Scaling
      and Root planning of Group II. Plasma OPN level was determined using a OPN Enzyme
      Immunometric Assay Kit (Quantikine). RESULTS: The mean value of plasma OPN levels
      in subjects with generalized chronic periodontitis was higher (153.08 ng/ml) as
      compared to the subjects with Healthy periodontium (55.09 ng/ml). After treatment
      of generalized chronic periodontitis group, the level of plasma OPN decreased to
      91.53 ng/ml. CONCLUSION: The findings from the study suggest that Plasma OPN
      levels were highest in plasma from sites with periodontal destruction; however,
      scaling and root planing resulted in the reduction of OPN levels.

PMID- 23162329
TI  - Salivary enzymes as diagnostic markers for detection of gingival/periodontal
      disease and their correlation with the severity of the disease.
AB  - CONTEXT: Host responses to periodontal disease include the production of
      different enzymes released by stromal, epithelial or inflammatory cells.
      Important enzymes associated with cell injury and cell death are aspartate
      aminotransferase, alanine aminotransferase (AST, ALT), alkaline phosphatase,
      acidic phosphatase (ALP, ACP), and gama glutamyl transferase (GGT). Changes in
      enzymatic activity reflect metabolic changes in the gingiva and periodontium, in
      the inflammation. AIMS: In this article we examined the activity of AST, ALT,
      GGT, ALP, and ACP in the saliva from patients with periodontal disease, before
      and after periodontal treatment (experimental group - 20 gingivitis patients and
      20 periodontitis patients), and in the saliva from healthy subjects (control
      group - 20 samples). SETTINGS AND DESIGN: Periodontal disease was determined
      based on the clinical parameters (gingival index (GI), probing depth (PD), and
      clinical attachment loss (CAL)). Patients with periodontal disease were under
      conventional periodontal treatment. MATERIALS AND METHODS: The stimulated saliva
      of the patient was collected in a sterile test tube and analyzed using the
      Automatic Analyzer. RESULTS: The obtained results showed statistically
      significant increased activity of AST, ALT, GGT, ALP, and ACP in the saliva from
      patients with periodontal disease, in relation to the control group. A
      significant reduction in the enzyme levels was seen after conventional
      periodontal therapy. CONCLUSIONS: Based on these results, it can be assumed that
      the salivary enzymes (AST, ALT, GGT, ALP, and ACP) can be considered as
      biochemical markers for evaluating the diagnosis and prognosis of the functional
      condition of periodontal tissues in disease and health, and in the evaluation of
      the therapy effects in periodontal disease.

PMID- 23162330
TI  - The effect of stress on periodontitis: A clinicobiochemical study.
AB  - BACKGROUND: Clinical and epidemiological data suggest that negative life
      experience events, like depression, may contribute to an increased susceptibility
      to periodontal disease. AIM: To study the association between psychological
      stress and chronic periodontitis. MATERIALS AND METHODS: One hundred and eleven
      dentate individuals, of age 40 years and above, were selected. The clinical
      examination included, the number of teeth present, plaque index, Probing Pocket
      Depth, and Clinical Attachment Level. Assessment of Psychological stress levels
      were done by a questionnaire and were correlated with salivary cortisol levels,
      which were estimated biochemically by using the Enzyme-Linked Immunosorbent Assay
      (ELISA) method. RESULTS: Statistical analysis was done by using the student 't'
      test and Mann Whitney test. According to our observation, chronic periodontitis
      showed a significant correlation with hypercortisolemia (P<0.0001), work tension
      (P=0.04), economic problems (P<0.0001), clinical stress syndrome (P<0.0001),
      plaque index (P<0.0001), and unsecured job (P=0.003). CONCLUSION: Stress may be
      considered as an important risk factor for periodontal disease. Routine salivary
      cortisol assessment may be an economical and useful diagnostic marker to rule out
      stress in periodontitis patients.

PMID- 23162331
TI  - Assessment of thickness of palatal mucosal donor site and its association with
      age and gender.
AB  - AIM: The purpose of the study is to determine the thickness of the palatal mucosa
      by a direct clinical method, and the association of age and gender with the
      thickness of the palatal mucosa. MATERIALS AND METHODS: Forty systemically and
      periodontally healthy Indian subjects participated in the study. The subjects
      were categorized according to age and gender. The thickness of the palatal mucosa
      was assessed by bone sounding. Acrylic stents provided 15 consistent locations
      for the measurement, defined according to the gingival margin and mid-palatal
      line. RESULTS: The mean thickness of palatal mucosa was 2.48?0.03 mm, ranging
      between 2.07 and 3.00 mm, among the participants. The younger age group had
      significantly thinner mucosa than the older age group. Females had thinner
      palatal mucosa than males, but not statistically significant. CONCLUSION: The
      palatal area from the distal line angle of the canine to the mesial line angle of
      the palatal root of the first molar provides sufficient donor tissue for grafting
      procedures. Factors such as body weight and genetic factors need to be further
      investigated. As the dimension of the soft tissue graft is an important factor
      influencing the success of the treatment procedure the assessment of the
      dimension is relevant to clinical periodontics.

PMID- 23162332
TI  - Efficacy of a new interdental cleaning aid.
AB  - BACKGROUND: It is now well established that removal of bacterial plaque can
      reduce the severity of chronic inflammatory periodontal disease. Periodontal
      disease is seen to progress faster interdentally and plaque control in these
      areas is of great importance. Various types of interdental cleaning aids have
      been developed in recent years. This study was aimed at evaluating the efficacy
      of a newly developed interdental cleaning aid, BrushPick, in a split mouth
      randomized clinical trial. MATERIALS AND METHODS: This was a split mouth design
      study where the quadrant on one side of the oral cavity served as the control
      while another quadrant on the opposite side served as the test sample. Fifty
      seven patients with mild-to-moderate periodontitis, presenting with open
      interdental embrasures, were selected for the study. After non-surgical
      periodontal therapy, they were asked to use the BrushPick in the embrasures on
      one side of the arch in a spilt mouth design study and the embrasures on the
      other side acted as controls. The Rustogi et al. modified Navy plaque index
      (RMNPI) and interdental bleeding index (IBI) were recorded at baseline, seven
      days, 14 days, and 28 days. STATISTICAL ANALYSIS: The mean differences between
      test and control sites were compared using the studentt test. The mean difference
      was compared between different durations using analysis of variance (ANOVA).
      RESULTS: The mean RMNPI was significantly different between the test and control
      sites at P<0.001 on both days 14 and 28. At 28 days the mean IBI was 0.08
      (SD=0.02) for the experimental sites and 0.28 (SD=0.11) for the control sites.
      The difference was statistically significant at P<0.001. ANOVA showed that the
      mean RMNPI scores and mean IBI scores showed a statistically significant
      difference when compared at different durations at the test sites (P<0.0001).
      But, at the control sites there was no significant change. CONCLUSION: This study
      suggested that BrushPick reduces plaque and gingival bleeding in open interdental
      embrasures. Further large sampled clinical trials and comparative studies using
      gold standard interdental cleaning aids are required to establish the efficacy of
      this device.

PMID- 23162333
TI  - Effect of insertion of xanthan-based chlorhexidine gel in the maintenance phase
      following the treatment of chronic periodontitis.
AB  - OBJECTIVES: The aim of this study was to evaluate the efficacy of subgingivally
      administered xanthan-based chlorhexidine gel when used in the maintenance phase
      following scaling and root planing (SRP) in the treatment of chronic
      periodontitis. MATERIALS AND METHODS: A randomized, controlled, single-center
      study was conducted involving 92 sites in 46 systemically healthy patients
      suffering from moderate to advanced chronic periodontitis with isolated pockets.
      The selected sites were randomized to two treatment arms: Group A (SRP alone) and
      Group B (SRP + insertion of chlorhexidine gel after 1 month). The gingival index,
      plaque index, probing pocket depth (PPD) and clinical attachment level (CAL) were
      recorded at baseline and subsequently after 1 month and 3 months. RESULTS: Both
      the groups showed significant reductions in PPD and CAL at both follow-up visits
      when compared with the baseline values (P<0.001). CONCLUSIONS: The results
      suggest that the application of xanthan based chlorhexidine gel following SRP in
      the maintenance phase might be beneficial in treatment of the chronic
      periodontitis in comparison to SRP alone. Greater improvements may be achieved
      when antimicrobial agents are used following SRP.

PMID- 23162334
TI  - Comparative evaluation of 0.1% turmeric mouthwash with 0.2% chlorhexidine
      gluconate in prevention of plaque and gingivitis: A clinical and microbiological
      study.
AB  - BACKGROUND: The aim of our clinical trial was to assess the efficacy of 0.1%
      turmeric mouthwash as an anti-plaque agent and its effect on gingival
      inflammation and to compare it with 0.2% chlorhexidine gluconate by evaluating
      the effect on plaque and gingival inflammation and on microbial load. MATERIALS
      AND METHODS: 60 subjects, 15 years and above, with mild to moderate gingivitis
      were recruited. Study population was divided into two groups. Group A-30 subjects
      were advised chlorhexidine gluconate mouthwash. Group B-30 subjects were advised
      experimental (turmeric) mouthwash. Both the groups were advised to use 10 ml of
      mouthwash with equal dilution of water for 1 min twice a day 30 min after
      brushing. Parameters were recorded for plaque and gingival index at day 0, on 14
      (th) day, and 21 (st) day. Subjective and objective criteria were assessed after
      14(th) day and 21(st) day. The N-benzoyl-l-arginine-p- nitroanilide (BAPNA) assay
      was used to analyze trypsin like activity of red complex microorganisms. RESULTS:
      On comparison between chlorhexidine and turmeric mouthwash, percentage reduction
      of the Plaque Index between 0 and 21 (st) day were 64.207 and 69.072,
      respectively (P=0.112), percentage reduction of Gingival Index between 0 and
      21(st) day were 61.150 and 62.545 respectively (P=0.595) and percentage reduction
      of BAPNA values between 0 and 21(st) day were 42.256 and 48.901 respectively
      (P=0.142). CONCLUSION: Chlorhexidine gluconate as well as turmeric mouthwash can
      be effectively used as an adjunct to mechanical plaque control in prevention of
      plaque and gingivitis. Both the mouthwashes have comparable anti-plaque, anti
      inflammatory and anti-microbial properties.

PMID- 23162335
TI  - Evaluation of efficacy of tetracycline fibers in conjunction with scaling and
      root planing in patients with chronic periodontitis.
AB  - AIM: The objective of this study was to compare the efficacy of scaling and root
      planing (SRP) alone versus tetracycline fiber therapy used adjunctively with SRP
      in the treatment of chronic periodontitis sites in maintenance patients.
      MATERIALS AND METHODS: A total of 30 patients with a diagnosis of chronic
      periodontitis (60 localized chronic periodontitis sites) in the age group of 35
      to 55 were selected. None of these patients had received any surgical or non
      surgical periodontal therapy and had sites of periodontal pockets measuring 4-7
      mm clinically and demonstrated radiographic evidence of moderate bone loss. Two
      non-adjacent sites in separate quadrants were selected in each patient for
      monitoring based on criteria that the sites had localized chronic periodontitis.
      Plaque index (PI) (sillness and loe) and Gingival-bleeding index (GI) (loe and
      sillness) were measured at baseline and 15(th), 30(th), 60(th), and 90(th)day.
      Clinical pocket depth (PD) and microbial analysis (MA) were analyzed at baseline
      and 90(th) day. RESULTS: At 0 and 3 months adjunctive tetracycline fiber therapy
      was significantly better in reducing PI, GBI, (P<0.001) than S and RP alone. In
      comparison, the reduction in the PD was non-significant at 0 and 3 months
      (P<0.001). The microbial analysis showed significant reduction in Porphyromonas
      gingivalis and Prevotella intermedia though there was no significant reduction in
      the Actinobacillus actinomycetemcomitans. CONCLUSION: Overall, these results
      indicate that fiber therapy significantly enhanced the effectiveness of SRP in
      the management of chronic periodontitis.

PMID- 23162336
TI  - Presence of Helicobacter pylori in subgingival plaque of periodontitis patients
      with and without dyspepsia, detected by polymerase chain reaction and culture.
AB  - BACKGROUND: Helicobacter pylori is an important gastrointestinal pathogen that is
      strongly associated with gastritis as well as peptic ulcer disease. Antimicrobial
      therapy frequently fails to cure H. pylori infection, which suggests there may be
      sanctuary sites where the organism resides. This study was aimed to assess the
      role of oral cavity as a reservoir of H. pylori by evaluating the occurrence of
      the organism in subgingival plaque of dyspeptic patients by polymerase chain
      reaction as well as culture. MATERIALS AND METHODS: Thirty chronic periodontitis
      patients whose biopsy specimens were found to be H. pylori positive with rapid
      urease test and histopathologic examination were considered as cases and 20
      chronic periodontitis patients who never had any symptoms of gastritis or peptic
      ulcer were taken as controls. Subgingival plaque samples were collected and sent
      to microbiological laboratory for detection of H. pylori by 16S rRNA based
      polymerase chain reaction as well as culture. RESULTS: 60% of the samples were
      found to be positive with polymerase chain reaction in the case group when
      compared to 15% in the controls. Also, 30% of the cases were found to be positive
      with culture compared to none in controls. CONCLUSION: A higher frequency of
      detection of H. pylori in those patients with positive antral biopsy report was
      seen. Also, polymerase chain reaction was found to be more sensitive than culture
      for detection. Thus, we conclude that detection of H. pylori in dental plaque of
      dyspeptic patients cannot be neglected and might represent a risk factor for
      recolonization of stomach after systemic eradication therapy.

PMID- 23162337
TI  - Treatment of grade II furcation involvement using resorbable guided tissue
      regeneration membrane: A six-month study.
AB  - AIMS: The present study was undertaken to evaluate the effectiveness of the
      combination of hydroxyapatite and beta-tricalcium phosphate bone alloplast with
      bioresorbable guided tissue regeneration membrane for the treatment of mandibular
      grade II furcation defects. SETTINGS AND DESIGN: A total of eight patients, four
      females and four males, in the age group of 18 to 65 years, with bilateral buccal
      grade II furcation defects in the mandibular molars, participated in the study.
      MATERIALS AND METHODS: THE FOLLOWING CLINICAL MEASUREMENTS WERE RECORDED AT
      BASELINE AS WELL AS THREE AND SIX MONTHS POST SURGERY: The Turesky-Gilmore
      Glickman modification of the Quigley Hein plaque index, the Loe and Silness
      gingival index, Relative Clinical Attachment Level Vertical Probing Depth in the
      mid-furcation area, and Horizontal Probing Depth in the mid-furcation area.
      STATISTICAL ANALYSIS: Pairwise comparisons within the groups were done by
      applying the independent student t test. Comparisons were also drawn between the
      test and the control groups by applying the independent student t test. RESULTS:
      The mean gain in the relative clinical attachment levels in the test and control
      groups, at the end of six months, were 2.50 and 1.63 mm, respectively. The mean
      change in the horizontal probing depth values at the end of six months in the
      test and control groups were 2.88 and 1.63 mm, respectively. The mean reduction
      in the vertical probing depth values in the test and control groups were 1.50 and
      1.38 mm, respectively. CONCLUSIONS: The resorbable GTR membrane with bone
      material was more effective than open debridement alone, in the treatment of
      furcation defects.

PMID- 23162338
TI  - A comparative clinical evaluation of acellular dermal matrix allograft and sub
      epithelial connective tissue graft for the treatment of multiple gingival
      recessions.
AB  - BACKGROUND: Obtaining predictable and aesthetic root coverage has become an
      important part of periodontal therapy. Several techniques have been developed to
      obtain these results with variable outcomes. The aim of this study was to compare
      and evaluate the effectiveness of acellular dermal matrix allograft (ADMA) and
      subepithelial connective tissue graft (SCTG) in combination with coronally
      positioned flap in the treatment of multiple gingival recessions in aesthetic
      areas. MATERIALS AND METHODS: Total 10 patients were selected for this study,
      aged between 18 to 40 years and were randomly assigned to one of the groups ADMA
      and SCTG. The clinical parameters including probing pocket depth, clinical
      attachment level, gingival recession, width of keratinized tissue were recorded
      at baseline and at 6 months after surgery and data was statistically analyzed.
      RESULTS: No significant differences in gingival recession reduction were noted
      between ADMA and gold - standard SCTG. Within limits of this clinical study, the
      use of ADMA may represent an acceptable alternative to the SCTG for treating
      gingival recession. The use of ADMA eliminates the need for the palatal donor
      site thus represents a less invasive surgery for treating multiple gingival
      recessions. CONCLUSIONS: These results suggest that ADMA may be a useful
      substitute instead of subepithelial connective tissue graft for root coverage.

PMID- 23162339
TI  - Dental health education through the brushing ROBOTUTOR: A new learning
      experience.
AB  - AIM: In the present study, a new electronic model ROBOTUTOR was designed to
      compare the efficacy of different modes of dental health education for
      demonstration of the Bass toothbrushing technique and also to evaluate its
      efficacy with different modes of dental health education in patient
      understanding. MATERIALS AND METHODS: Total 150 subjects were randomized into two
      groups, Group 1 (Questionnaire) and Group II (Investigators). Subjects with
      history of gingivitis and only mild periodontitis were included. Demonstration of
      Bass technique was given to each subject with the help of three different modes,
      i.e., ROBOTUTOR, clinician, and audio-video aids. RESULTS: The result was
      evaluated in terms of effectiveness, ease of understanding, attraction, and
      recollection. In the present study, the best mode of education is clinician
      demonstration and the least effective one is the audio-video mode. In contrast,
      the ROBOTUTOR model was found to be more attractive than the other two.
      CONCLUSION: Although demonstration by clinician is the best, it is time consuming
      and not feasible for community purpose. ROBOTUTOR would thus save clinician's
      chair side time and help in effective demonstration of the brushing technique.

PMID- 23162340
TI  - Oral hygiene and periodontal status of teenagers with special needs in the
      district of Nalgonda, India.
AB  - OBJECTIVES: To assess oral hygiene status, oral hygiene practices and periodontal
      status among 14-17-year-old visually impaired, deaf and dumb, intellectually
      disabled and physically challenged and normal teenagers in the district of
      Nalgonda, South India. MATERIALS AND METHODS: Seven hundred and fifty teenagers
      in the age group of 14-17 years, constituting visually impaired, deaf and dumb,
      intellectually disabled, physically challenged and normal teenagers, were
      studied. Oral hygiene status and periodontal status were assessed using clinical
      indices and compared. RESULTS: Among the five groups chosen for the study, the
      intellectually disabled group had the highest plaque scores and poor oral
      hygiene. The visually impaired and deaf and dumb had better oral hygiene compared
      with other disability groups. Physically handicapped showed higher loss of
      attachment scores and deleterious and parafunctional habits. Normal teenagers had
      good oral hygiene and lower plaque scores. Oral health status relied basically on
      proper use of oral hygiene aids and training of the groups by their care takers.
      CONCLUSION: Disabled groups showed poor oral hygiene and higher incidence of
      periodontal disease, which may be attributed to the lack of coordination,
      understanding, physical disability or muscular limitations. Hence, more attention
      needs to be given to the dental needs of these individuals through ultimate,
      accurate and appropriate prevention, detection and treatment.

PMID- 23162341
TI  - Prevalence of dentine hypersensitivity: A cross-sectional study in rural Punjabi
      Indians.
AB  - AIMS AND OBJECTIVES: To study the prevalence of dentine hypersensitivity and
      related risk factors in rural population of Punjab, India. MATERIALS AND METHODS:
      A total of 650 subjects reporting dentine sensitivity were included in the study
      comprising of 270 males and 380 females. All the subjects completed an interview
      and the subjects reporting dentine hypersensitivity were examined further using
      air syringe to put a blast of air to confirm the diagnosis of dentine
      hypersensitivity. Periodontal attachment loss and gingival recession of all the
      sensitive teeth were examined and recorded. RESULTS: The prevalence of dentine
      hypersensitivity was 25% in the oral test. The subjects receiving the treatment
      of hypersensitivity were only 15.1%. The older group in the 50-59 years had the
      highest number (98%) of subjects with dentine hypersensitivity. Most commonly
      affected teeth were mandibular incisors. The other factors related to dentine
      hypersensitivity were the socioeconomic status, lower education level, and access
      to dental care. The periodontal factors related to hypersensitivity were gingival
      recession and poor oral hygiene. CONCLUSIONS: The prevalence of dentine
      hypersensitivity was 25% in the rural population of Punjab.

PMID- 23162342
TI  - Prevalence of gingival enlargement secondary to calcium channel blockers in
      patients with cardiovascular diseases.
AB  - AIM: The purpose of the present study was to determine the prevalence and extent
      of gingival overgrowth in patients treated with calcium channel blockers for
      cardiovascular diseases. BACKGROUND: Calcium channel blockers are widely used in
      the treatment of hypertension, vasoplastic angina, and cardiacarrythmias.
      Gingival overgrowth resulting from the use of calcium channel blockers is of
      primary concern to dentists. The purpose of the present study is to determine the
      prevalence and extent of gingival overgrowth in patients treated with calcium
      channel blockers for various cardiovascular diseases, to assess their periodontal
      status and to correlate the factors like age, sex, duration, dosage, type of
      drugs that result in gingival overgrowth. MATERIALS AND METHODS: A cross
      sectional study was done in cardiac patients treated with calcium channel
      blockers, visiting The Railway hospital, Perumbur, Chennai. Information regarding
      medical history, type, duration, dosage of medication were recorded and analyzed.
      The periodontal condition of the patients was assessed using the plaque index,
      gingival index, calculus index, papillary bleeding index, and extent of gingival
      overgrowth using appropriate indices. The data was later subjected to statistical
      analysis. RESULTS: In this study, a total of 213 cardiac patients (145 males and
      68 females) who met the inclusion and exclusion criteria were screened. The
      patients were between 19 and 69 years. CONCLUSIONS: From the results of the
      present study it can be concluded that gingival overgrowth does occur with
      calcium channel blockers. Elderly males appeared to be more susceptible to the
      development of drug-induced gingival overgrowth, which was independent of dosage,
      duration of drug administered but the presence of local factors seemed to
      aggravate the same.

PMID- 23162343
TI  - Two stage surgical procedure for root coverage.
AB  - Gingival recession may present problems that include root sensitivity, esthetic
      concern, and predilection to root caries, cervical abrasion and compromising of a
      restorative effort. When marginal tissue health cannot be maintained and
      recession is deep, the need for treatment arises. This literature has documented
      that recession can be successfully treated by means of a two stage surgical
      approach, the first stage consisting of creation of attached gingiva by means of
      free gingival graft, and in the second stage, a lateral sliding flap of grafted
      tissue to cover the recession. This indirect technique ensures development of an
      adequate width of attached gingiva. The outcome of this technique suggests that
      two stage surgical procedures are highly predictable for root coverage in case of
      isolated deep recession and lack of attached gingiva.

PMID- 23162344
TI  - Clinical attachment level gain and bone regeneration around a glass ionomer
      restoration on root surface wall of periodontal pocket.
AB  - A case describing perio-restorative management of an accidental trauma in the mid
      portion of root on an upper left canine tooth following an ostectomy surgery is
      presented here. The traumatized root area was undergoing fast resorption and a
      chronic periodontal abscess had developed in relation to the lesion. The article
      illustrates the clinical and radiographic photo series of a periodontal flap
      surgery done to gain access into a subgingival region for the placement of Glass
      ionomer restoration on the root and its periodic follow up. The clinical
      condition of the area suggests 8 mm clinical attachment gain over the restoration
      and the review radiographs at definite intervals up to 18 months revealed
      evidence of consistent bone regeneration around the restoration. The article also
      highlights the various other possibilities, where this restorative material can
      be effectively used in conjunction with periodontal surgical procedures.

PMID- 23162345
TI  - Horizontal ridge augmentation using a combination approach.
AB  - Resorption of alveolar bone - a common sequel of tooth loss jeopardizes the
      functional and esthetic outcome of treatment, especially in the maxillary
      anterior areas. Therefore, augmentation of deficient alveolar ridges is an
      important aspect of dental implant therapy. A case of severe maxillary ridge
      deficiency successfully treated with horizontal ridge augmentation to facilitate
      implant placement is described. Ridge augmentation was achieved using a
      combination of autogenous block graft, particulate grafting, and guided bone
      regeneration (GBR). Follow-up was done next day, after ten days, three months,
      and six months. Various approaches can be followed in order to achieve an
      increase in the ridge width. In our case, we used a combination of different
      techniques for ridge augmentation. A significant improvement in ridge width was
      noticed at six months thus facilitating the placement of implants.

PMID- 23162346
TI  - Periodontal manifestations of patients with Turner's syndrome: Report of 3 cases.
AB  - Complete or partial absence of the second sex chromosome, with or without a
      mosaic karyotype, is detected in approximately 1 per 2,500 live-born females.
      Such a cytogenetic finding coupled with clinical features, such as short stature
      and ovarian failure, supports the diagnosis of Turner's syndrome (TS). It is
      typically characterized by the combination of physical features and cytogenetics
      in females. The presenting clinical features can vary widely among affected
      individuals. Consequently, whereas short stature and gonadal dysgenesis are
      almost universal in TS, many other organ systems are affected to varying degrees
      and at different stages of life. The periodontal status of three females
      diagnosed with TS has been reported here.

PMID- 23162347
TI  - Buccinator muscle repositioning.
AB  - Anatomical aberrations and abnormalities are frequently associated with
      functional, psychosocial, and emotional problems. One such aberration is crestal
      attachment of frenum or muscle on the alveolar processes of the jaws. Crestal
      attachment of buccinator muscle is a rare phenomenon, which may pose various
      problems in routine oral exercises/functions or restoring the edentulous area. A
      case of abnormal buccinator muscle attachment is presented here, which was
      relocated apically by surgical means using an acrylic stent. The healing was
      uneventful and significant apical repositioning was observed. A fixed bridge was
      fabricated and the long-term results of the restorative therapy were assured
      because the patient could maintain the oral hygiene well after the muscle
      repositioning operation.

PMID- 23162348
TI  - Odontogenic myxoma presenting as localized inflammatory gingival enlargement: A
      diagnostic dilemma.
AB  - Odontogenic myxoma (OM) is a rare and locally invasive benign neoplasm found
      exclusively in the maxillofacial region. The radiographic and clinical features
      are variable, and the diagnosis is therefore not easy. A case of OM of the
      maxilla is described in a 19-year-old female, previously diagnosed as
      inflammatory gingival enlargement. Clinical, histological, radiographic, and
      computed tomographic (CT) scan assessments were done, which were confirmatory for
      OM. Surgical excision of the lesion was done. The patient was put on periodic
      recall, as the recurrence rate of the lesion was high. The biological spectrum of
      OM was highly variable and diagnosis at an early stage was very difficult.
      Gingival enlargement presentation might not always be an inflammatory reaction.
      All possible differential diagnosis should be explored and various diagnostic
      tools utilized, to screen the enlargement.

PMID- 23162349
TI  - Gingival cyst of adult: A rare case.
AB  - Gingival cyst of adult is an uncommon cyst of gingival soft tissue occurring in
      either the free or attached gingiva. This odontogenic epithelial cyst is most
      frequently seen near mandibular canine and premolar region, believed to represent
      the soft tissue counter part of the lateral periodontal cyst. This article
      presents a case of gingival cyst treated with exicisional biopsy followed by
      histopathological confirmation and an emphasis on the clinical aspects of this
      lesion.

PMID- 23162350
TI  - Orofacial granulomatosis: A case report with review of literature.
AB  - Orofacial granulomatosis (OFG) encompasses conditions characterized by non
      necrotizing granulomatous inflammation of the oral and maxillofacial region that
      present clinically as labial enlargement, perioral and/or mucosal swelling, oral
      ulcerations, and gingivitis. The unifying term "OFG" has been introduced to
      integrate the spectrum of various disorders, including Melkersson-Rosenthal
      syndrome and granulomatous cheilitis (which is sometimes considered to be a
      monosymptomatic form of Melkersson-Rosenthal syndrome), and has been shown to be
      associated with Crohn's disease, sarcoidosis, and infectious diseases such as
      tuberculosis. Although various etiological agents such as food substances, food
      additives, dental materials, and various microbiological agents have been
      implicated in the disease process, its precise pathogenesis is yet to be
      elucidated. Delayed type of hypersensitivity reaction appears to play a
      significant role, although the exact antigen inducing the immunological reaction
      varies in individual patients. However, evidence for the role of genetic
      predisposition to the disease is sparse. The underlying immunological mechanism
      appears to show some similarities between OFG and Crohn's disease, emphasizing
      the need for more comparative studies of the two entities. The aim of this
      article is to report a case of OFG, along with a detailed literature review of
      the facts and variations associated with its nomenclature, clinical presentation,
      and etiology. It also projects the challenges that a professional has to face in
      the diagnosis and treatment planning of such cases.

PMID- 23162351
TI  - Capillary hemangioma of palatal mucosa.
AB  - Hemangiomas are common tumors characterized microscopically by proliferation of
      blood vessels. The congenital hemangioma is often present at birth and may become
      more apparent throughout life. They are probably developmental rather than
      neoplastic in origin. Despite their benign origin and behavior, hemangiomas in
      the oral cavity are always of clinical importance to the dental profession and
      require appropriate clinical management. This case report presents a case of
      capillary hemangioma of anterior palatal mucosa in a 13-year-old female.

PMID- 23162352
TI  - From the Editor's desk.

PMID- 23162353
TI  - Ectopic pregnancy after infertility treatment.
AB  - Early pregnancy complications are more common in women who conceive after
      infertility treatment. Most of these occur before 12 weeks of gestation and
      include miscarriage, vaginal bleeding, intrauterine hematoma, vanishing twin, and
      ectopic pregnancy (EP). The incidence of EPs following infertility treatment is
      much higher compared with that in spontaneous pregnancies. The occurrence of an
      EP is very distressing to an infertile couple, who has lots of hopes pinned on
      the treatment outcome, especially because of the cost incurred and the physical
      and mental trauma both have gone through during the treatment process. The
      association between infertility and EP is complex, as it can be a consequence of
      infertility as well as a cause. The two principal risk factors for an EP are
      genital tract infections and tubal surgeries. Though several etiologies are
      proposed, but patients with tubal factor infertility are at an increased risk of
      an EP. Earlier diagnosis of EP helps to improve prognosis and optimize subsequent
      fertility. It is pivotal to evaluate the likelihood of subsequent occurrence of
      an EP and be too vigilant when treating. The correct choice of the treatment
      modality should be made to prevent the recurrence. The early prediction of the
      pregnancy outcome therefore has great importance for both the couple and
      clinician. Today with the help of sensitive beta human chorionic gonadotropin
      (beta-hCG) assays and transvaginal sonography, one can diagnose an EP prior to
      symptoms, and conservative treatment for the preservation of the fallopian tube
      is possible. Conservative management in the form of expectant and medical
      management should be considered as a first-line treatment modality, provided that
      the overall clinical picture suggests that it is safe to do so. If not,
      laparoscopic management of EPs appears to be the favored approach of management
      as compared to laparotomy.

PMID- 23162354
TI  - Effects of metformin use in pregnant patients with polycystic ovary syndrome.
AB  - Use of metformin throughout pregnancy in women with polycystic ovary syndrome
      (PCOS) has shown to reduce the rates of early pregnancy loss, preterm labor, and
      prevention of fetal growth restriction. Metformin has been shown to have
      encouraging effects on several metabolic aspects of polycystic ovarian syndrome,
      such as insulin sensitivity, plasma glucose concentration and lipid profile and
      since women with PCOS are more likely than healthy women to suffer from pregnancy
      related problems like early pregnancy loss, gestational diabetes mellitus and
      hypertensive states in pregnancy, the use of metformin therapy in these patients
      throughout pregnancy may have beneficial effects on early pregnancy loss and
      development of gestational diabetes.

PMID- 23162355
TI  - Letrozole in a low-cost in vitro fertilization protocol in intracytoplasmic sperm
      injection cycles for male factor infertility: A randomized controlled trial.
AB  - INTRODUCTION: Letrozole, a selective aromatase inhibitor, reduces the total dose
      of gonadotrophin required for inducing follicular maturation. We evaluated if
      incorporation of letrozole could be an effective alternative for low-cost in
      vitro fertilization (IVF) protocol particularly in intracytoplasmic sperm
      injection (ICSI) cycles where male factor infertility is the sole indication for
      IVF. MATERIALS AND METHODS: It is a randomized controlled single-blind trial. 94
      women with history of severe male factor infertility were selected. 42 women
      (study group) received letrozole, 5 mg daily from day 3-7 and recombinant FSH
      (rFSH) 75IU/day from day 5 continuously till hCG injection. 52 women (control
      group) underwent continuous stimulation by rFSH (150-225IU/day) from day 2. GnRH
      antagonist (Inj. Orgalutran 0.25 ml sub-cutaneous) was started at maximum
      follicle size of 14 in both groups. Ovulation was triggered by 10,000IU of hCG
      followed by IVF-ET. Main outcome measures were total dose of rFSH (IU/cycle),
      terminal E2 (pg/ml), number of mature follicles, number of oocyte retrieved,
      transferable embryo, endometrial thickness, pregnancy rate and mean expenditure.
      Statistical analysis is done by using SPSS11. RESULTS: As compared to control
      group (1756 +/- 75IU), the study group i.e., Let-rFSH received (625 +/- 98IU)
      significantly lower (P = 0.0001) total dose of rFSH. Terminal E2 was
      significantly lower (P = 0.0001) in study group than control (830 +/- 36 vs. 1076
      +/- 41 pg/ml) with significant increment in endometrial thickness (P = 0.0008) in
      study group, (9.1 +/- 0.32 vs. 8.7 +/- 0.69) which maintained an improved
      pregnancy rate though nonsignificant. The risk of hyperstimulation had
      significantly (P = 0.01) reduced in study group than control (0 vs. 7).Treatment
      outcome in all other aspects including pregnancy rate were statistically
      comparable. Per cycle mean expenditure was reduced by 34% in study group than
      control. CONCLUSION: Adjunctive use of letrozole may be an effective mean of low
      cost IVF therapy.

PMID- 23162356
TI  - Evaluation of the rabbit as an experimental model for human uterine synechia.
AB  - CONTEXT: Pathogenesis of uterine synechia remains unsolved, the causal
      relationship between synechia and infertility is not clearly established. AIMS:
      To evaluate the rabbit as an experimental model for Asherman's syndrome using the
      endometrial curettage as trigger mechanism then to evaluate its impact on
      fertility. SETTINGS AND DESIGN: Experimental study MATERIALS AND METHODS: 13
      female rabbits. All submitted traumatic endometrial curettage. Animals of Group 1
      (n = 7) were sacrificed at various times following surgery (day 7, 15 and 30),
      animals of Group 2 (n = 6) were bred and sacrificed during pregnancy. Main
      outcome were synechia occurring, number of implanted fetus, lumen surface/ global
      horn perimeter ratio (LS-GHP ratio) and epithelium thickness. STATISTICAL
      ANALYSIS: Means were compared using Student 't' test (P < 0.05 was considered
      significant). Number of implantation sites of two horns were compared with the
      Wilcoxon test. RESULTS: No synechia have been observed. Examinations at Day 7, 15
      and 30 demonstrate a complete regeneration of endometrium. We observed a
      significant diminished LS-GHP ratio at day 7 (0.042 +/- 0.004 vs 0.074 +/- 0.002
      mm; P = 0.013) with a higher simple columnar epithelium compared to control (16.6
      +/- 3.39 vs 10.98 +/- 1.7; P = 0.001). We observed a diminished ovum implantation
      in traumatized horns, even if it was not statistically significant. CONCLUSION:
      Even if no intrauterine adhesion were observed, this model represents a
      pathogenesis condition in the rabbit similar to intrauterine adhesions observed
      in the human with negative impact on implantation.

PMID- 23162357
TI  - A prospective study of GnRH long agonist versus flexible GnRH antagonist protocol
      in PCOS: Indian experience.
AB  - BACKGROUND: Polycystic ovarian syndrome is a common endocrine disorder of
      reproductive age women. Many controlled ovarian stimulation (COS) strategies have
      been offered for the treatment of patients with PCOS undergoing in vitro
      fertilization, but the optimal protocol is still a controversy. There is no
      compelling evidence for the advantage of one stimulation protocol over the other.
      MATERIALS AND METHODS: This is a single-center prospective controlled study
      comparing long agonist and antagonist protocol in PCOS women. RESULTS: There was
      no significant difference in live birth rate and clinical pregnancy rate. Rate of
      ovarian hyperstimulation syndrome was significantly higher in the agonist group.
      Number of oocytes retrieved, number of follicles and peak estradiol levels were
      significantly more in the agonist group. CONCLUSION: The GnRH antagonist protocol
      is an equally effective but safer protocol in PCOS patients compared with the
      long agonist protocol.

PMID- 23162358
TI  - Assessment of oocyte quality in polycystic ovarian syndrome and endometriosis by
      spindle imaging and reactive oxygen species levels in follicular fluid and its
      relationship with IVF-ET outcome.
AB  - OBJECTIVES: The aim of this study is to examine meiotic spindle in oocytes along
      with reactive oxygen species (ROS) levels in follicular fluid of women undergoing
      IVF and to correlate these findings with embryo quality and pregnancy outcome.
      MATERIALS AND METHODS: 167 women aged 25-35 years with endometriosis (Group A),
      polycystic ovarian syndrome (PCOS) (Group B) and tubal block (Group C) were
      included. Long protocol downregulation using recombinant follicular stimulating
      hormone was used for ovarian stimulation. Aspirated follicular fluid containing
      mature oocytes were analyzed for ROS levels and the oocytes were assessed for the
      presence of meiotic spindle using Cri-OosightTM Polscope. Fertilization, embryo
      quality, endometrial assessment, and final pregnancy outcome were assessed.
      RESULTS: Meiotic spindles were visualized in a higher proportion of mature
      oocytes retrieved from women with endometriosis (66%) as compared to those with
      PCOS (50.5%) and tubal block (62.3%). ROS levels were also observed to be
      significantly less in the follicular fluid of oocytes in women with endometriosis
      (Group A) as compared to the other two groups (P <= 0.001). However, pregnancy
      rates were observed to be lower in Group A (32%) than Groups B (39%) and C (44%),
      respectively. Within each group, oocytes with spindle visualization yielded a
      higher number of Grade 1 embryos (P < 0.05) as well as lower ROS levels in
      follicular fluid (P <= 0.001) as compared to those where spindle could not be
      visualized. CONCLUSIONS: There was good correlation between spindle imaging and
      ROS levels as reliable predictors of oocyte assessment. Women with endometriosis
      had low ROS levels and good spindle imaging results suggesting a possible role of
      endometrial receptivity accounting for lower pregnancy rates in these women. Poor
      oocyte quality, as reflected by higher mean ROS levels and low number of oocytes
      with spindle visualization, could be the factor impeding pregnancy in women with
      PCOS as compared to women with tubal block.

PMID- 23162359
TI  - Overt leptin response to controlled ovarian hyperstimulation negatively
      correlates with pregnancy outcome in in vitro fertilization--embryo transfer
      cycle.
AB  - CONTEXT: A critical body mass of adipose tissue is essential for the normal
      development of female reproductive functions. Leptin, an adipocyte-derived
      hormone encoded by the 'Ob' gene has been proposed as a peripheral signal
      indicating the adequacy of nutritional status for reproductive functions. It is
      reported as a direct regulator of gametogenic and steroidogenic potential of
      ovary. Though leptin is widely present in reproductive tissues, its relationship
      to reproductive hormones is still poorly understood. AIMS: Present investigation
      attempts to explore ovarian response to secretory profile of leptin and its
      impact on pregnancy outcome in women undergoing controlled ovarian
      hyperstimulation for in vitro fertilization and embryo transfer (IVF-ET).
      SETTINGS AND DESIGN: Patients enrolled for IVF-ET underwent pituitary-ovarian
      suppression by 'Long Protocol' GnRH-agonist downregulation followed by ovarian
      stimulation. MATERIALS AND METHODS: Sera were procured at different phases of IVF
      ET for the assay of estradiol, progesterone, human chorionic gonadotropin, and
      for leptin. Ovarian follicular fluids were also assayed for leptin. Luteinized
      granulosa cells were cultured in vitro to evaluate their steroidogenic potential.
      STATISTICAL ANALYSIS USED: Statistical analyses were done by student's t-test,
      ANOVA, and Chi-square tests as applicable. All results were expressed as Mean +/-
      SE. P values < 0.05 were considered significant. RESULTS: Positive correlation
      was observed between serum and ovarian follicular fluid leptin. A negative
      correlation was noted between the serum leptin levels and endometrial thickness.
      CONCLUSIONS: Elevated leptin response may exert adverse impacts on pregnancy
      success during IVF-ET possibly by modulating uterine receptivity.

PMID- 23162360
TI  - The role of Allium cepa on aluminum-induced reproductive dysfunction in
      experimental male rat models.
AB  - AIM: Reproductive toxicity is a major challenge associated with aluminum (Al)
      exposure. Studies that associated Al with reproductive dysfunction did not
      account for the possible influence of Allium cepa extract. This study, therefore,
      investigates the influence of A. cepa on aluminum-induced reproductive
      dysfunction. MATERIALS AND METHODS: SIX MALE RATS PER GROUP WERE ASSIGNED TO ONE
      OF THE FOLLOWING FOUR TREATMENT GROUPS: The control animals were on control diet.
      A. cepa-treated rats received 1 ml of the extract/100 g body weight (BW), Al
      treated rats received 100 mg AlCl(3) /kg BW, and A.cepa+Al received 1 ml of the
      extract/100 g BW plus 100 mg AlCl(3) /kg BW. Rats were orally administered their
      respective doses. A. cepa treatment was for 8 weeks, while Al treatment was for
      the last 3 days of the experimental period. RESULTS: Results obtained showed that
      Al significantly decreased (P < 0.05) plasma testosterone, follicular stimulating
      hormone (FSH), luteinizing hormone (LH), sperm count, motility, morphology and
      viability, superoxide dismutase (SOD) and catalase (CAT) activities, while lipid
      peroxidation index [malondialdehyde (MDA)] was significantly (P < 0.05)
      increased. Reproductive hormones (except testosterone), sperm qualities, and
      enzymatic antioxidants were significantly (P < 0.05) increased in A. cepa-treated
      rats and A. cepa plus Al-treated rats, while MDA was significantly (P < 0.05)
      improved. Weights of testes were comparable in all groups. CONCLUSION: It is thus
      suggested that Al exerts reproductive dysfunction by oxidative damage. A. cepa
      antagonizes the toxic effects of AlCl(3) and improves the antioxidant status and
      sperm quality of male rat. However, testosterone level did not increase with A.
      cepa treatment.

PMID- 23162362
TI  - Heterotopic pregnancy with successful pregnancy outcome.
AB  - A heterotopic pregnancy is a rare complication of pregnancy, in which both extra
      uterine and intrauterine gestation occur simultaneously. We hereby report a case
      of ruptured heterotopic pregnancy presenting at 6weeks of gestation and was
      managed with immediate laparatomy. The intrauterine pregnancy course was
      uneventful with delivery of a healthy baby at term by Caesarean section.

PMID- 23162361
TI  - Anti-mullerian hormone cut-off values for predicting poor ovarian response to
      exogenous ovarian stimulation in in-vitro fertilization.
AB  - OBJECTIVES: (a) To establish the cut-off levels for anti-Mullerian hormone (AMH)
      in a population of Indian women that would determine poor response. (b) To
      determine which among the three ie.,: age, follicle stimulating hormone (FSH), or
      AMH, is the better determinant of ovarian reserve. STUDY DESIGN: Prospective
      observational study. SETTING: In vitro fertilization (IVF) unit of a tertiary
      hospital. MATERIALS AND METHODS: The inclusion criterion was all women who
      presented to the center for in-vitro fertilization/Intracytoplasmic sperm
      injection (IVF/ICSI). The exclusion criteria were age >45 years, major medical
      illnesses precluding IVF or pregnancy, FSH more than 20 IU/L, and failure to
      obtain consent. The interventions including baseline pelvic scan, day 2/3 FSH,
      luteinizing hormone (LH), estradiol estimations, and AMH measurement on any
      random day of cycle were done. Subjects underwent IVF according to long agonist
      or antagonist protocol regimen. Oocyte recovery was correlated with studied
      variables. The primary outcome measure was the number of oocytes aspirated (OCR).
      Three categories of ovarian response were defined: poor response, OCR <= 3;
      average response, OCR between 4 and 15; hyperresponse, OCR > 15. RESULTS: Of the
      198 patients enrolled, poor, average, and hyperresponse were observed in 23%,
      63%, and 14% respectively. Correlation coefficient for AMH with ovarian response
      was r = 0.591. Area under the curve (AUCs) for poor response for AMH, subject's
      age, and FSH were 0.768, 0.624, and 0.635, respectively. The discriminatory level
      of AMH for prediction of absolute poor response was 2 pmoL/l, with 98%
      specificity and 20% sensitivity. CONCLUSIONS: AMH fares better than age and FSH
      in predicting the overall ovarian response and poor response, though it cannot be
      the absolute predictor of non-responder status. A level of 2 pmol/l is
      discriminatory for poor response.

PMID- 23162363
TI  - Persistent mullerian duct syndrome in a patient with bilateral cryptorchid testes
      with seminoma.
AB  - Persistent mullerian duct syndrome (PMDS) is a rare form of male
      pseudohermaphroditism in which mullerian duct derivatives are present in an
      otherwise normally differentiated 46 XY male. We report a case of a 33-year-old
      male with PMDS operated for postchemotherapy seminoma. A diagnosis of PMDS was
      made on subsequent histopathological evaluation.

PMID- 23162364
TI  - A rare cause for primary amenorrhoea.
AB  - Gonadal (ovarian) dysgenesis with normal chromosomes (46, XX), XX female gonadal
      dysgenesis (XX-GD) is a rare genetically heterogeneous disorder. In 1951,
      Perrault reported the association of gonadal dysgenesis and deafness, now
      referred to as Perrault's syndrome. Perrault syndrome is a rare autosomal
      recessive condition affecting both females and males; only females have gonadal
      dysgenesis associated with sensorineural deafness, which is present in both
      sexes. We present a case of sporadic Perrault syndrome in a 35-year-old female
      with primary amenorrhea, sensorineural deafness, marfanoid features and normal
      karyotype. There are very few case reports describing the condition, even lesser
      reports of association with marfanoid habitus. We report this case for its rarity
      and add to the spectrum of the disease that remains undetermined.

PMID- 23162365
TI  - A rare case of recurrent pregnancy loss associated with high-titer positivity for
      perinuclear anti-neutrophilic cytoplasmic antibodies.
AB  - We present a case of recurrent pregnancy loss associated with unusual
      constellation of utoimmunity-related features such as hypertension, severe
      hrombocytopenia, hypothyroidism and persistent high titers of perinuclear
      antineutrophilic cytoplasmic antibodies. Her clinical features did not fit into a
      particular diagnosis of vasculitides, systemic lupus erythematosis (SLE) or other
      known autoimmune diseases where this autoantibody is found in high titers. We
      report the unusual association of this autoantibody with recurrent early fetal
      demise in this case.

PMID- 23162367
TI  - Kisspeptin: Role in reproduction and implications for infertility management.

PMID- 23162366
TI  - Heterotropic pregnancy: Rare occurrence of a 12- week ruptured right isthmo
      cornual ectopic along with a viable intrauterine pregnancy.
AB  - Heterotropic pregnancy, although a rare condition, is associated with a greater
      frequency in assisted reproduction. It occurs in approximately 1 in 100
      pregnancies conceived by in vitro fertilization (IVF) particularly when multiple
      embryos are transferred into the uterus. We report a case of heterotropic
      pregnancy following IVF with the rupture of an isthmo-cornual pregnancy at 12
      weeks of gestation with uneventful progression of the intrauterine pregnancy.
      Laparotomy was performed for the excision of the isthmo-cornual pregnancy. The
      intrauterine pregnancy continued uneventfully. A female baby was delivered by
      elective cesarean section at 33 weeks.

PMID- 23162368
TI  - Alcohol and fertility.

PMID- 23162369
TI  - Transformational Teaching: Theoretical Underpinnings, Basic Principles, and Core
      Methods.
AB  - Approaches to classroom instruction have evolved considerably over the past 50
      years. This progress has been spurred by the development of several learning
      principles and methods of instruction, including active learning, student
      centered learning, collaborative learning, experiential learning, and problem
      based learning. In the present paper, we suggest that these seemingly different
      strategies share important underlying characteristics and can be viewed as
      complimentary components of a broader approach to classroom instruction called
      transformational teaching. Transformational teaching involves creating dynamic
      relationships between teachers, students, and a shared body of knowledge to
      promote student learning and personal growth. From this perspective, instructors
      are intellectual coaches who create teams of students who collaborate with each
      other and with their teacher to master bodies of information. Teachers assume the
      traditional role of facilitating students' acquisition of key course concepts,
      but do so while enhancing students' personal development and attitudes toward
      learning. They accomplish these goals by establishing a shared vision for a
      course, providing modeling and mastery experiences, challenging and encouraging
      students, personalizing attention and feedback, creating experiential lessons
      that transcend the boundaries of the classroom, and promoting ample opportunities
      for preflection and reflection. We propose that these methods are synergistically
      related and, when used together, maximize students' potential for intellectual
      and personal growth.

PMID- 23162370
TI  - Can Organized Youth Activities Protect Against Internalizing Problems Among
      Adolescents Living in Violent Homes?
AB  - Using longitudinal data from a subsample of Hispanic, African American, and white
      youth enrolled in the Project on Human Development in Chicago Neighborhoods (N =
      1,419), we examined the effects of both parental involvement in domestic violence
      and youth participation in organized out-of-school-time activities on
      internalizing symptoms during adolescence. We also examined the extent to which
      participation in organized activities protected youth against the internalizing
      consequences of domestic violence. We found that intensive participation in
      either afterschool programs or extracurricular activities was inversely
      associated with youth internalizing problems. Moreover, we found that intensive
      participation in afterschool programs weakened the association between parents'
      domestic violence and youths' internalizing problems.

PMID- 23162371
TI  - Adolescent Work and Alcohol Use Revisited: Variations by Family Structure.
AB  - Previous research finds adolescent work hours to be associated with increased
      alcohol use. Most studies, however, fail to account for possible selection
      effects that lead youth to both work and substance use. Using data from the first
      two waves of the National Longitudinal Study of Adolescent Health (N = 12,620), a
      fixed effects regression method is employed to control for stable between-person
      differences neglected by previous studies. Results show little relationship
      between work hours and alcohol use when controlling for individual heterogeneity.
      Results reveal variations, however, by family structure, with work hours being
      negatively associated with alcohol use among those from single-parent households.
      Although exhibiting significant main effects, family and peer processes fail to
      account for differences by family structure.

PMID- 23162372
TI  - The Social Cognition of Social Foraging: Partner Selection by Underlying
      Valuation.
AB  - Humans and other animals have a variety of psychological abilities tailored to
      the demands of asocial foraging, that is, foraging without coordination or
      competition with other conspecifics. Human foraging, however, also includes a
      unique element, the creation of resource pooling systems. In this type of social
      foraging, individuals contribute when they have excess resources and receive
      provisioning when in need. Is this behavior produced by the same psychology as
      asocial foraging? If so, foraging partners should be judged by the same criteria
      used to judge asocial patches of resources: the net energetic benefits they
      provide. The logic of resource pooling speaks against this. Maintaining such a
      system requires the ability to judge others not on their short-term returns, but
      on the psychological variables that guide their behavior over the long-term. We
      test this idea in a series of five studies using an implicit measure of
      categorization. Results showed that (1) others are judged by the costs they incur
      (a variable not relevant to asocial foraging) whereas (2) others are not judged
      by the benefits they provide when benefits provided are unrevealing of underlying
      psychological variables (despite this variable being relevant to asocial
      foraging). These results are suggestive of a complex psychology designed for both
      social and asocial foraging.

PMID- 23162373
TI  - Burden of constipation-predominant irritable bowel syndrome (IBS-C) in France,
      Italy, and the United Kingdom.
AB  - BACKGROUND: Several studies have examined the effect of irritable bowel syndrome
      (IBS) on health outcomes in Western Europe, but less research has focused on the
      constipation subtype (IBS-C). The current study addresses this gap by comparing
      patients with IBS-C and matched controls for health status, work productivity,
      and resource utilization. METHODS: Data were obtained from the 2010 5EU National
      Health and Wellness Survey (NHWS), which includes respondents from France,
      Germany, Italy, Spain, and the UK. Only participants from France (n = 15,051),
      Italy (n = 7580), and the UK (n = 15,065) were included in the analyses.
      Respondents who reported a physician diagnosis of IBS and reported only
      constipation symptoms were compared with respondents who did not report being
      diagnosed with IBS using a propensity score-matching methodology (matching on
      sociodemographics, health behaviors, and comorbidities). Differences between
      patients with IBS-C and matched controls were examined on health status (Short
      Form Survey Instrument version 2), work productivity (Work Productivity and
      Activity Impairment questionnaire), and health care resource use in the past 6
      months. RESULTS: A total of 83 (0.55%), 109 (1.44%), and 204 (1.35%) respondents
      reported a diagnosis of IBS with only constipation symptoms in France, Italy, and
      the UK, respectively. Within each country, patients with IBS-C reported
      significantly worse health status compared with matched controls (all P < 0.05)
      and significantly more physician visits (all P < 0.05). More hospitalizations
      were also observed in the UK (P < 0.05). Among those who were employed, patients
      with IBS-C in France and the UK also reported significantly more presenteeism
      than matched controls (all P < 0.05). CONCLUSION: These findings highlight the
      pervasive influence of IBS-C on the day-to-day functioning of sufferers, their
      ability to be productive at work, and their influence on the wider health care
      system. Significant unmet needs remain, and improved management of this condition
      could result in significant and clinically meaningful gains in health status as
      well as alleviating a societal cost burden.

PMID- 23162374
TI  - Association of cognitive judgment and shyness with frequency and quality of flow
      experience.
AB  - OBJECTIVE: To determine the association of cognitive judgment and shyness with
      frequency and quality of flow experience. DESIGN AND METHODS: This was a cross
      sectional survey of the relationship between psychological tendency and frequency
      and quality of flow experience in 68 college students, undertaken in Hiroshima,
      Japan. The predictors were Shyness Scale scores, measure of ambiguity tolerance
      scores, and Life Orientation Test scores, and the outcome was the frequency and
      quality of flow experience. RESULTS: The results of the binary logistic
      regression analysis indicated that only the measure of ambiguity tolerance (P =
      0.02, odds ratio = 1.06, and 95% confidence interval = 1.01-1.11) was a predictor
      of the quality of flow experience, and only the Shyness Scale (P = 0.007, odds
      ratio = 0.95, and 95% confidence interval = 0.91-0.98) was a predictor of the
      frequency of flow experience. CONCLUSION: The findings suggest that ambiguity
      tolerance and shyness are associated with the frequency and quality of the flow
      experience.

PMID- 23162376
TI  - Colloidal stability of polymeric nanoparticles in biological fluids.
AB  - Estimating the colloidal stability of polymeric nanoparticles (NPs) in biological
      environments is critical for designing optimal preparations and to clarify the
      fate of these devices after administration. To characterize and quantify the
      physical stability of nanodevices suitable for biomedical applications, spherical
      NPs composed of poly-lactic acid (PLA) and poly-methyl-methacrylate (PMMA), in
      the range 100-200 nm, were prepared. Their stability in salt solutions,
      biological fluids, serum and tissue homogenates was analyzed by dynamic light
      scattering (DLS). The PMMA NPs remained stable in all fluids, while PLA NPs
      aggregated in gastric juice and spleen homogenate. The proposed stability test is
      therefore useful to see in advance whether NPs might aggregate when administered
      in vivo. To assess colloidal stability ex vivo as well, spectrophotofluorimetric
      analysis was employed, giving comparable results to DLS.

PMID- 23162375
TI  - The use of brain imaging to elucidate neural circuit changes in cocaine
      addiction.
AB  - Within substance abuse, neuroimaging has experienced tremendous growth as both a
      research method and a clinical tool in the last decade. The application of
      functional imaging methods to cocaine dependent patients and individuals in
      treatment programs, has revealed that the effects of cocaine are not limited to
      dopamine-rich subcortical structures, but that the cortical projection areas are
      also disrupted in cocaine dependent patients. In this review, we will first
      describe several of the imaging methods that are actively being used to address
      functional and structural abnormalities in addiction. This will be followed by an
      overview of the cortical and subcortical brain regions that are most often cited
      as dysfunctional in cocaine users. We will also introduce functional connectivity
      analyses currently being used to investigate interactions between these cortical
      and subcortical areas in cocaine users and abstainers. Finally, this review will
      address recent research which demonstrates that alterations in the functional
      connectivity in cocaine users may be associated with structural pathology in
      these circuits, as demonstrated through diffusion tensor imaging. Through the use
      of these tools in both a basic science setting and as applied to treatment
      seeking individuals, we now have a greater understanding of the complex cortical
      and subcortical networks which contribute to the stages of initial craving,
      dependence, abstinence, and relapse. Although the ability to use neuroimaging to
      predict treatment response or identify vulnerable populations is still in its
      infancy, the next decade holds tremendous promise for using neuroimaging to
      tailor either behavioral or pharmacologic treatment interventions to the
      individual.

PMID- 23162377
TI  - Self-reported sleep patterns, sleep problems, and behavioral problems among
      school children aged 8-11 years.
AB  - OBJECTIVES: Investigation of sleep patterns, sleep problems, and behavioral
      problems in 8- to 11-year-old children.  METHODS: A total of 330 children (age:
      M=9.52; SD=0.56; range=8-11 years; 47.3% girls) in the 4th grade of elementary
      school in Salzburg (Austria) completed a self-report questionnaire (80 items) to
      survey sleep patterns, sleep problems, and behavioral problems.  RESULTS:
      Children aged 8-11 years slept approximately 10 h and 13 min on school days
      (SD=47 min) as well as on weekends (SD=81 min); girls slept significantly longer
      on weekends than boys. Most common self-reported sleep problems were dryness of
      the mouth (26.6%), sleep onset delay (21.9%), bedtime resistance (20.3%), and
      restless legs (19.4%). There was a significant association between watching TV as
      well as playing computer games prior to sleep with frightful dreams. Daytime
      sleepiness indicated by difficulty waking up (33.4%) and having a hard time
      getting out of bed (28.5%) was also very prominent. However, children in Salzburg
      seemed to be less tired during school (6.6%) or when doing homework (4.8%)
      compared to other nationalities. Behavioral problems (e.g., emotional symptoms,
      hyperactivity and inattention, conduct problems, peer problems) and daytime
      sleepiness were both significantly associated with sleep problems: the more sleep
      problems reported, the worse behavioral problems and daytime sleepiness were.
      Moreover, we could show that sharing the bed with a pet was also related to sleep
      problems.  CONCLUSIONS: Self-reported sleep problems among 8- to 11-year-old
      children are very common. There is a strong relationship between sleep disorders
      and behavioral problems. Routine screening and diagnosis as well as treatment of
      sleep disorders in school children should, therefore, be established in the
      future.

PMID- 23162378
TI  - Favorable Protonation of the (MU-edt)[Fe(2)(PMe(3))(4)(CO)(2)(H-terminal)](+)
      Hydrogenase Model Complex Over Its Bridging MU-H Counterpart: A Spectroscopic and
      DFT Study.
AB  - The mechanism of hydrogen production in [FeFe] hydrogenase remains elusive.
      However, a species featuring a terminal hydride bound to the distal Fe is thought
      to be the key intermediate leading to hydrogen production. In this study, density
      functional theory (DFT) calculations on the terminal (H-term) and bridging (MU-H)
      hydride isomers of (MU-edt)-[Fe(2)(PMe(3))(4)(CO)(2)H](+) are presented in order
      to understand the factors affecting their propensity for protonation. Relative to
      H-term, MU-H is 12.7 kcal/mol more stable, which contributes to its decreased
      reactivity towards an acid. Potential energy surface (PES) calculations for the
      reaction of the H-term isomer with 4-nitropyridinium, a proton source, further
      reveal a lower activation energy barrier (14.5 kcal/mol) for H-term than for MU-H
      (29 kcal/mol). Besides these energetic considerations, the H-term isomer displays
      a key molecular orbital (MO <139>) that has a relatively strong hydride (1s)
      contribution (23%), which is not present in the MU-H isomer. This indicates a
      potential orbital control of the reaction of the hydride complexes with acid. The
      lower activation energy barrier and this key MO together control the overall
      catalytic activity of (MU-edt)[Fe(2)(PMe(3))(4)(CO)(2)(H-term)](+). Lastly, Raman
      and IR spectroscopy were performed in order to probe the nu(Fe-H) stretching mode
      of the two isomers and their deuterated counterparts. A nu(Fe-H) stretching mode
      was observed for the MU-H complex at 1220 cm(-1). However, the corresponding mode
      is not observed for the less stable H-term isomer.

PMID- 23162379
TI  - Sleeping Arrangements in Families with Twins.
AB  - This paper describes home sleeping arrangements used by parents of twins and
      investigates whether room sharing (twins in the same room as parents) or
      cobedding (crib-sharing between twins) influences parental night time sleep
      duration or sleep quality. A secondary analysis of data obtained from a
      longitudinal study of sleep in 104 families with twins was undertaken. Over 65%
      of twins were cobedded at 4 weeks; this decreased to approximately 42% by 13
      weeks of age. Approximately 64% of families practiced room sharing at 4 weeks,
      this decreased to approximately 40% by 13 weeks of age. Mothers and fathers who
      both room shared and cobedded their twins at 9 weeks of age were most likely to
      experience restricted sleep duration when compared to other sleeping
      arrangements. Results suggest that parents of twins may not be following the most
      recent AAP recommendations regarding safe infant sleep for multiple birth
      infants.

PMID- 23162380
TI  - Epigenetic and Neurodevelopmental Perspectives on Variation in Parenting
      Behavior.
AB  - Mother-infant interactions in rodents can be used to explore the biological basis
      of postnatal parental effects. There is emerging evidence from laboratory studies
      that variation in early life experiences can induce molecular changes in the
      developing brain which lead to activation or silencing of genes. These epigenetic
      effects may account for the stability of the effects of parenting on offspring
      development and the transmission of parenting from one generation to the next. In
      this article, we highlight evidence supporting a role for epigenetic mechanisms
      in the consequences, transmission, and variability in parenting. Although
      primarily drawn from laboratory studies in rodents, this evidence may also
      provide some insights into key questions within the study and practice of human
      parenting. We discuss these questions, highlighting both the challenges and
      benefits of using translational approaches.

PMID- 23162381
TI  - The Role of Parenting in the Emergence of Human Emotion: New Approaches to the
      Old Nature-Nurture Debate.
AB  - Emotions are complex processes that are essential for survival and adaptation.
      Recent studies of children and animals are shedding light on how the developing
      brain learns to rapidly respond to signals in the environment, assess the
      emotional significance of this information, and in so doing adaptively regulate
      subsequent behavior. Here, I describe studies of children and nonhuman primates
      who are developing within emotionally aberrant environments. Examining these
      populations provides new insights on the ways in which the social or
      interpersonal contexts of parenting may influence development of the neural
      systems underlying emotional behavior.

PMID- 23162382
TI  - Investigation of the Polymeric Properties of alpha-Synuclein and Comparison with
      NMR Experiments: A Replica Exchange Molecular Dynamics Study.
AB  - Intrinsically disordered proteins (IDPs) have been shown to be involved in a
      number of cellular functions, in addition to their predominance in diseased
      states. alpha-synuclein may be described as one such IDP implicated in the
      pathology of Parkinson's disease. Understanding the conformational
      characteristics of the monomeric state of alpha-synuclein is necessary for
      understanding the role of the monomer conformation in aggregation. Polymer
      theories have been applied to investigate the statistical properties of
      homopolymeric IDPs. Here we use Replica Exchange Molecular Dynamics (REMD)
      simulations using temperature as a proxy for solvent quality to examine how well
      these theories developed for homopolymeric chains describe heteropolymeric alpha
      synuclein. Our results indicate that alpha-synuclein behaves like a homopolymer
      at the extremes of solvent quality, while in the intermediate solvent regime, the
      uneven distribution of charged residues along the sequence strongly influences
      the conformations adopted by the chain. We refine the ensemble extracted from the
      REMD simulations of alpha-synuclein, which shows the best qualitative agreement
      with experiment, by fitting to the experimental NMR Residual Dipolar Couplings
      (RDCs) and Paramagnetic Relaxation Enhancements (PREs). Our results demonstrate
      that the detailed shape of the RDC patterns are sensitive to the angular
      correlations that are local in sequence while longer range anti-correlations
      which arise from packing constraints affect the RDC magnitudes.

PMID- 23162383
TI  - Charge Optimization Theory for Induced-Fit Ligands.
AB  - The design of ligands with high affinity and specificity remains a fundamental
      challenge in understanding molecular recognition and developing therapeutic
      interventions. Charge optimization theory addresses this problem by determining
      ligand charge distributions that produce the most favorable electrostatic
      contribution to the binding free energy. The theory has been applied to the
      design of binding specificity as well. However, the formulations described only
      treat a rigid ligand-one that does not change conformation upon binding. Here, we
      extend the theory to treat induced-fit ligands for which the unbound ligand
      conformation may differ from the bound conformation. We develop a thermodynamic
      pathway analysis for binding contributions relevant to the theory, and we
      illustrate application of the theory using HIV-1 protease with our previously
      designed and validated subnanomolar inhibitor. Direct application of rigid charge
      optimization approaches to nonrigid cases leads to very favorable intramolecular
      electrostatic interactions that are physically unreasonable, and analysis shows
      the ligand charge distribution massively stabilizes the preconformed (bound)
      conformation over the unbound. After analyzing this case, we provide a treatment
      for the induced-fit ligand charge optimization problem that produces physically
      realistic results. The key factor is introducing the constraint that the free
      energy of the unbound ligand conformation be lower or equal to that of the
      preconformed ligand structure, which corresponds to the notion that the unbound
      structure is the ground unbound state. Results not only demonstrate the
      applicability of this methodology to discovering optimized charge distributions
      in an induced-fit model, but also provide some insights into the energetic
      consequences of ligand conformational change on binding. Specifically, the
      results show that, from an electrostatic perspective, induced-fit binding is not
      an adaptation designed to enhance binding affinity; at best, it can only achieve
      the same affinity as optimized rigid binding.

PMID- 23162384
TI  - Tunable, mixed-resolution modeling using library-based Monte Carlo and graphics
      processing units.
AB  - Building on our recently introduced library-based Monte Carlo (LBMC) approach, we
      describe a flexible protocol for mixed coarse-grained (CG)/all-atom (AA)
      simulation of proteins and ligands. In the present implementation of LBMC,
      protein side chain configurations are pre-calculated and stored in libraries,
      while bonded interactions along the backbone are treated explicitly. Because the
      AA side chain coordinates are maintained at minimal run-time cost, arbitrary
      sites and interaction terms can be turned on to create mixed-resolution models.
      For example, an AA region of interest such as a binding site can be coupled to a
      CG model for the rest of the protein. We have additionally developed a hybrid
      implementation of the generalized Born/surface area (GBSA) implicit solvent model
      suitable for mixed-resolution models, which in turn was ported to a graphics
      processing unit (GPU) for faster calculation. The new software was applied to
      study two systems: (i) the behavior of spin labels on the B1 domain of protein G
      (GB1) and (ii) docking of randomly initialized estradiol configurations to the
      ligand binding domain of the estrogen receptor (ERalpha). The performance of the
      GPU version of the code was also benchmarked in a number of additional systems.

PMID- 23162385
TI  - The Covariate's Dilemma.

PMID- 23162387
TI  - Serious thoughts about plagiarism from India.

PMID- 23162389
TI  - Comparison of caudal analgesia between ropivacaine and ropivacaine with clonidine
      in children: A randomized controlled trial.
AB  - BACKGROUND: Addition of clonidine to ropivacaine (0.2%) can potentially enhance
      analgesia without producing prolonged motor blockade. The aim of the present
      study was to compare the post-operative pain relieving quality of ropivacaine
      0.2% and clonidine mixture to that of plain ropivacaine 0.2% following caudal
      administration in children. METHODS: In a prospective, double-blinded, randomized
      controlled trial, 30 ASA 1 pediatric patients undergoing infraumbilical surgery
      were randomly allocated to receive a caudal injection of either plain ropivacaine
      0.2% (1 ml/kg) (group A) or a mixture of ropivacaine 0.2% (1 ml/kg) with
      clonidine 2 MUg/kg (group B). Objective pain score and need for supplemental
      analgesics were compared during the 1(st) 24 hours postoperatively. Residual post
      operative sedation and motor blockade were also assessed. RESULTS: Significantly
      prolonged duration of post-operative analgesia was observed in group B
      (P<0.0001). Heart rate and blood pressure were not different in 2 groups. Neither
      motor blockade nor post-operative sedation varied significantly between the
      groups. CONCLUSION: The combination of clonidine (2 MUg/kg) and ropivacaine 0.2%
      was associated with an improved quality of post-operative analgesia compared to
      plain 0.2% ropivacaine. The improved analgesic quality of the clonidine
      ropivacaine mixture was achieved without causing any significant degree of post
      operative sedation or prolongation of motor blockade.

PMID- 23162386
TI  - Neuropharmacology of Sleep and Wakefulness: 2012 Update.
AB  - The development of sedative/hypnotic molecules has been empiric rather than
      rational. The empiric approach has produced clinically useful drugs but for no
      drug is the mechanism of action completely understood. All available
      sedative/hypnotic medications have unwanted side effects and none of these
      medications creates a sleep architecture that is identical to the architecture of
      naturally occurring sleep. This chapter reviews recent advances in research
      aiming to elucidate the neurochemical mechanisms regulating sleep and
      wakefulness. One promise of rational drug design is that understanding the
      mechanisms of sedative/hypnotic action will significantly enhance drug safety and
      efficacy.

PMID- 23162388
TI  - Anesthesia for thoracic surgery: a survey of middle eastern practice.
AB  - PURPOSE: The main objective of this survey is to describe the current practice of
      thoracic anesthesia in the Middle Eastern (ME) region. METHODS: A prospective
      online survey. An invitation to participate was e-mailed to all members of the ME
      thoracic-anaesthesia group. A total of 58 members participated in the survey from
      19 institutions in the Middle East. Questions concerned ventilation strategies
      during one-lung ventilation (OLV), anesthesia regimen, mode of postoperative
      analgesia, use of lung isolation techniques, and use of i.v. fluids. RESULTS:
      Volume-controlled ventilation was favored over pressure-controlled ventilation
      (62% vs 38% of respondents, P<0.05); 43% report the routine use of positive end
      expiratory pressure. One hundred percent of respondents report using double-lumen
      tube (DLT) as a first choice airway to establish OLV. Nearly a third of
      respondents, 31.1%, report never using bronchial blocker (BB) in their thoracic
      anesthesia practice. Failure to pass a DLT and difficult airway are the most
      commonly cited indications for BB use. Regarding postoperative analgesia, the
      majority 61.8% favor thoracic epidural analgesia over other techniques (P<0.05).
      CONCLUSIONS: Our survey provides a contemporary snapshot of the ME thoracic
      anesthetic practice.

PMID- 23162390
TI  - Comparison between intrathecal morphine with paravertebral patient controlled
      analgesia using bupivacaine for intraoperative and post-thoracotomy pain relief.
AB  - OBJECTIVES: This study was designed to compare the intrathecal morphine and
      paravertebral block with bupivacaine given before induction of anesthesia for
      intra-operative and post-thoracotomy pain relief for 48 hours using patient
      controlled paravertebral analgesia in post-operative period. METHODS: After taken
      an approval from the ethics committee of the University, 40 patients were
      randomly assigned to receive either preservative-free intrathecal morphine 0.3 mg
      in 3 ml normal saline together with paravertebral block (group I) or
      paravertebral block alone using bupivacaine (group II) before an induction of
      anesthesia. No continuous infusion of bupivacaine was started in both groups.
      Primary outcomes were Visual Analogue Score (VAS) at rest and on coughing.
      Hemodynamic and respiratory effects, bupivacaine consumption, patient's
      satisfaction, and side effects like nausea, vomiting, urinary retention, and
      itching were considered as secondary outcomes. All patients in both groups
      received paracetamol 1 gram (gm) IV every 6 hourly for the 1(st) 24 hr. Amount of
      rescue analgesic (pethidine 0.5 mg/kg IV) in both groups and total bupivacaine
      cumulative doses in 48 hrs were calculated. RESULTS: VAS at rest and on coughing
      did not differ significantly between the 2 groups at 0, 1, 6, 12, 18, 24, and 48
      hours (P= >0.1). At 24 hours, VAS increased in both the groups, but the increase
      in VAS was comparable in both groups. There were insignificant incidences of
      nausea, purities, and urinary retention in intrathecal group compared with
      paravertebral group. The other side effects and patient satisfaction did not show
      any statistical significant difference between 2 groups. CONCLUSION: Intrathecal
      morphine 0.3 mg is safe and effective way to improves pain control for thoracic
      surgery and was comparable to paravertebral patient control analgesia (PPCA) with
      bupivacaine for the 1(st) 48 hours post-thoracotomy.

PMID- 23162391
TI  - A randomized, clinical trial of ketorolac tromethamine vs ketorolac trometamine
      plus complex B vitamins for cesarean delivery analgesia.
AB  - BACKGROUND: Ketorolac is widely used for postoperative analgesia in patients who
      undergo cesarean delivery. In countries where the use of opioids is considerably
      restricted, alternatives to narcotics are required. AIM: We hypothesize that the
      addition of complex B synergize the analgesic effect of ketorolac in
      postoperative cesarean patients, thus requiring a smaller dose of the anti
      inflammatory agent, and therefore decreasing the potential side effects of
      ketorolac. METHODS: A randomized clinical trial with 100 patients undergoing a
      primary elective cesarean delivery enrolled in the study. Pain was assessed in
      the recovery room and then they were randomized to receive ketorolac 30 mg
      intramuscular (i.m.) or 15 mg of ketorolac plus complex B vitamin (CBV). The pain
      score with an analog scale was assessed 1, 2, 6, 12, 18, and 24 h after the
      baseline. The student's t test was performed to compare the demographic
      differences between the 2 means. RESULTS: 100 patients were included in the
      study, showing no statistical differences in the demographics. The patient's pain
      score at 1, 2, 6, 12, 18 and 24 hours showed no statistical differences between
      the control group (ketorolac 30mg) compared to the group of ketorolac 15mg and
      complex B vitamins. No changes in the coagulation studies were found in both
      groups. CONCLUSION: The present study demonstrates that ketorolac 30 mg and
      ketorolac 15 mg plus complex B vitamins can provide acceptable analgesia in many
      patients with severe pain.

PMID- 23162392
TI  - Hemodynamic changes during robotic radical prostatectomy.
AB  - BACKGROUND: Effect on hemodynamic changes and experience of robot-assisted
      laparoscopic radical prostatectomy (RALRP) in steep Trendelenburg position (45
      degrees ) with high-pressure CO(2) pneumoperitoneum is very limited. Therefore,
      we planned this prospective clinical trial to study the effect of steep
      Tredelenburg position with high-pressure CO(2) pneumoperitoneum on hemodynamic
      parameters in a patient undergoing RALRP using FloTrac/VigileoTM1.10. METHODS:
      After ethical approval and informed consent, 15 patients scheduled for RALRP were
      included in the study. In the operation room, after attaching standard monitors,
      the radial artery was cannulated. Anesthesia was induced with fentanyl (2 MUg/kg)
      and thiopentone (4-7 mg/kg), and tracheal intubation was facilitated by
      vecuronium bromide (0.1 mg/kg). The patient's right internal jugular vein was
      cannulated and the Pre SepTM central venous oximetry catheter was connected to
      it. Anesthesia was maintained with isoflurane in oxygen and nitrous oxide and
      intermittent boluses of vecuronium. Intermittent positive-pressure ventilation
      was provided to maintain normocapnea. After CO(2) pneumoperitoneum, position of
      the patient was gradually changed to 45 degrees  Trendelenburg over 5 min. The
      robot was then docked and the robot-assisted surgery started. Intraoperative
      monitoring included central venous pressure (CVP), stroke volume (SV), stroke
      volume variation (SVV), cardiac output (CO), cardiac index (CI) and central
      venous oxygen saturation (ScvO(2)). RESULTS: After induction of anesthesia, heart
      rate (HR), SV, CO and CI were decreased significantly from the baseline value
      (P>0.05). SV, CO and CI further decreased significantly after creating
      pneumoperitoneum (P>0.05). At the 45 degrees  Trendelenburg position, HR, SV, CO
      and CI were significantly decreased compared with baseline. Thereafter, CO and CI
      were persistently low throughout the 45 degrees  Trendelenburg position
      (P=0.001). HR at 20 min and 1 h, SV and mean arterial blood pressure after 2 h
      decreased significantly from the baseline value (P>0.05) during the 45 degrees 
      Trendelenburg position. CVP increased significantly after creating
      pneumoperitoneum and at the 45 degrees  Trendelenburg position (after 5 and 20
      min) compared with the baseline postinduction value (P>0.05). All these
      parameters returned to baseline after deflation of CO(2) pneumoperitoneum in the
      supine position. There were no significant changes in SVV and ScvO(2) throughout
      the study period. CONCLUSIONS: The steep Trendelenburg position and CO(2)
      pneumoperitoneum, during RALRP, leads to significant decrease in stroke volume
      and cardiac output.

PMID- 23162393
TI  - Dexmedetomidine premedication for fiberoptic intubation in patients of
      temporomandibular joint ankylosis: A randomized clinical trial.
AB  - BACKGROUND: Fiberoptic intubation is the gold standard technique for difficult
      airway management in patients of temporomandibular joint. This study was aimed to
      evaluate the clinical efficacy and safety of dexmedetomidine as premedication
      with propofol infusion for fiberoptic intubation. METHODS: Consent was obtained
      from 46 adult patients of temporomandibular joint ankylosis, scheduled for gap
      arthroplasty. They were enrolled for thisdouble-blind, randomized, prospective
      clinical trial with two treatment groups - Group D and Group P, of 23 patients
      each. Group D patients had received premedication of dexmedetomidine 1 MUg/kg
      infused over 10 min followed by sedative propofol infusion and the control Group
      P patients were given only propofol infusion to achieve sedation. Condition
      achieved at endoscopy, intubating conditions, hemodynamic changes and
      postoperative events were evaluated as primary outcome. RESULTS: The fiberoptic
      intubation was successful with satisfactory endoscopic and intubating condition
      in all patients. Dexmedetomidine premedication has provided satisfactory
      conditions for fiberoptic intubation and attenuated the hemodynamic response of
      fiberoptic intubation than the propofol group. CONCLUSION: Fiberoptic intubation
      was found to be easier with dexmedetomidine premedication along with sedative
      infusion of propofol with complete amnesia of the procedure, hemodynamic
      stability and preservation of patent airway.

PMID- 23162394
TI  - Comparison of three supraglottic devices in anesthetised paralyzed children
      undergoing elective surgery.
AB  - CONTEXT: The newest variation of the i-gel supraglottic airway is a pediatric
      version. AIMS: This study was designed to investigate the usefulness of the size
      2 i-gel compared with the ProSeal laryngeal mask airway (PLMA) and classic
      laryngeal mask airway (cLMA) of the same size in anesthetized, paralyzed
      children. SETTINGS AND DESIGN: A prospective, randomized, single-blinded study
      was conducted in a tertiary care teaching hospital. METHODS: Ninety ASA grade I
      II patients undergoing lower abdominal, inguinal and orthopedic surgery were
      included in this prospective study. The patients were randomly assigned to the i
      gel, PLMA and cLMA groups (30 patients in each group). Size 2 supraglottic airway
      was inserted according to the assigned group. We assessed ease of insertion,
      hemodynamic data, oropharyngeal sealing pressure and postoperative complications.
      RESULTS: There were no differences in the demographic and hemodynamic data among
      the three groups. The airway leak pressure of the i-gel group (27.1+/-2.6
      cmH(2)O) was significantly higher than that of the PLMA group (22.73+/-1.2
      cmH(2)O) and the cLMA group (23.63+/-2.3 cmH(2)O). The success rates for first
      attempt of insertion were similar among the three devices. There were no
      differences in the incidence of postoperative airway trauma, sore throat or
      hoarse cry in the three groups. CONCLUSIONS: Hemodynamic parameters, ease of
      insertion and postoperative complications were comparable among the i-gel, PLMA
      and cLMA groups, but airway sealing pressure was significantly higher in the i
      gel group.

PMID- 23162395
TI  - Effect of adding dexamethasone to bupivacaine on transversus abdominis plane
      block for abdominal hysterectomy: A prospective randomized controlled trial.
AB  - PURPOSE: Different adjuvants have been used to improve the quality and increase
      the duration of local anesthetics during various nerve block techniques. The
      current study was aimed to evaluate the effect of adding dexamethasone to
      bupivacaine on the quality and duration of transversus abdominis plane (TAP)
      block. METHODS: Sixty adult patients undergoing elective open abdominal
      hysterectomy were randomly allocated to receive TAP block using 20 mL of
      bupivacaine hydrochloride 0.25% + 2 mL saline 0.9% (control group, n=30) or 20 mL
      of bupivacaine hydrochloride 0.25% + 2 mL dexamethasone "8 mg" (dexamethasone
      group, n=30). The primary outcome was postoperative pain, as evaluated by visual
      analog scale (VAS) for pain scoring at 1, 2, 4, 12, 24 and 48 h postoperatively,
      whereas the secondary outcomes were time to first analgesia (TFA), morphine
      consumption and the occurrence of nausea, vomiting or somnolence. RESULTS: The
      pain VAS score was significantly lower at the postoperative 2 h (4.9 vs. 28.1,
      P=0.01), 4 h (12.2 vs. 31.1, P=0.01) and 12 h (15.7 vs. 25.4, P=0.02).
      Furthermore, TFA was significantly longer in the dexamethasone group (459.8 vs.
      325.4 min, P=0.002), with lesser morphine requirements in the postoperative 48 h
      (4.9 vs. 21.2 mg, P=0.003) and lower incidence of nausea and vomiting (6 vs. 14,
      P=0.03). No complications attributed to the block were recorded. CONCLUSION:
      Addition of dexamethasone to bupivacaine in TAP block prolonged the duration of
      the block and decreased the incidence of nausea and vomiting.

PMID- 23162396
TI  - Live donor hepatectomy for liver transplantation in Egypt: Lessons learned.
AB  - PURPOSE: To retrospectively review anesthesia and intensive care management of
      145 consented volunteers subjected to right lobe or left hepatectomy between 2003
      and 2011. METHODS: After local ethics committee approval, anesthetic and
      intensive care charts, blood transfusion requirements, laboratory data,
      complications and outcome of donors were analyzed. RESULTS: One hundred and forty
      three volunteers successfully tolerated the surgery with no blood transfusion
      requirements, but with a morbidity rate of (50.1%). The most frequent
      complication was infection (21.1%) (intraabdominal collections), followed by
      biliary leak (18.2%). Two donors had major complications: one had portal vein
      thrombosis (PVT) treated with vascular stent. This patient recovered fully. The
      other donor had serious intraoperative bleeding and developed postoperative PVT
      and liver and renal failure. He died after 12 days despite intensive treatment.
      He was later reported among a series of fatalities from other centers worldwide.
      Epidural analgesia was delivered safely (n=90) with no epidural hematoma despite
      significantly elevated prothrombin time (PT) and international normalization
      ratio (INR) postoperatively, reaching the maximum on Day 1 (16.9+/-2.5 s and
      1.4+/-0.2, P<0.05 when compared with baseline). Hypophosphatemia and
      hypomagnesemia were frequently encountered. Total Mg and phosphorus blood levels
      declined significantly to 1.05+/-0.18 mg/dL on Day 1 and 2.3+/-0.83 mg/dL on Day
      3 postoperatively. CONCLUSIONS: Coagulation and electrolytes need to be monitored
      perioperatively and replaced adequately. PT and INR monitoring postoperatively is
      still necessary for best timing of epidural catheter removal. Live donor
      hepatectomy could be performed without blood transfusion. Bile leak and
      associated infection of abdominal collections requires further effort to better
      identify biliary leaks and modify the surgical closure of the bile ducts. Donor
      hepatectomy is definitely not a complication-free procedure; reported
      complication risks should be available to the volunteers during consenting.

PMID- 23162397
TI  - Perioperative predictors of morbidity and mortality following cardiac surgery
      under cardiopulmonary bypass.
AB  - BACKGROUND: Prediction of outcome after cardiac surgery is difficult despite a
      number of models using pre-, intra- and post-operative factors. Ideally, risk
      factors operating in all three phases of the patients' stay in the hospital
      should be incorporated into any outcome prediction model. The aim of the present
      study was to identify the perioperative risk factors associated with morbidity,
      mortality and length of stay in the recovery room (LOSR) and length of stay in
      the hospital (LOSH). METHODS: Eighty-eight adults of either sex, patients
      undergoing elective open cardiac surgery were studied prospectively. The ability
      of a number of pre-, intra- and post-operative factors to predict outcome in the
      form of mortality, immediate morbidity (LOSR) and intermediate morbidity (LOSH)
      was assessed. RESULTS: Factors associated with higher mortality were preoperative
      prothrombin index (PTI), American Society of Anesthesiology-Physical Status (ASA
      PS) grade, Cardiac Anaesthesia Risk Evaluation (CARE) score and New York Heart
      Association (NYHA) class, intraoperative duration of cardiopulmonary bypass
      (DCPB), number of inotropes used while coming off cardiopulmonary bypass and
      postoperatively, Acute Physiology and Chronic Health Evaluation (APACHE) II
      excluding the Glassgow Comma Scale (GCS) component and the number of inotropes
      used. Immediate morbidity was associated with preoperative PTI, inotrope usage
      intra- and post-operatively and the APACHE score. Intermediate morbidity was
      associated with DCPB and intra- and post-operative inotrope usage. Individual
      surgeon influenced the LOSR and the LOSH. CONCLUSION: APACHE score, a general
      purpose severity of illness score, was relatively ineffective in the
      postoperative period because of sedation, neuromuscular blockade and elective
      ventilation used in a number of these patients. The preoperative and
      intraoperative factors like CARE, ASA-PS grade, NYHA, DCPB and number of
      inotropes used influencing morbidity and mortality are consistent with the
      literature, despite the small size of our sample.

PMID- 23162398
TI  - Comparison of the use of McCoy and TruView EVO2 laryngoscopes in patients with
      cervical spine immobilization.
AB  - CONTEXT: The cervical spine has to be stabilized in patients with suspected
      cervical spine injury during laryngoscopy and intubation by manual in-line axial
      stabilization. This has the propensity to increase the difficulty of intubation.
      An attempt has been made to compare TruView EVO2 and McCoy with cervical spine
      immobilization, which will aid the clinician in choosing an appropriate device
      for securing the airway with an endotracheal tube (ETT) in the clinical scenario
      of trauma. AIMS: To compare the effectiveness of TruView EVO2 and McCoy
      laryngoscopes when performing tracheal intubation in patients with neck
      immobilization using manual in-line axial cervical spine stabilization. SETTINGS
      AND DESIGN: K. M. C. Hospital, Mangalore, This was a randomized control clinical
      trial. METHODS: Sixty adult patients of either sex of ASA physical status 1 and 2
      who were scheduled to undergo general anesthesia with endotracheal intubation
      were studied. Comparison of intubation difficulty score (IDS), hemodynamic
      response, Cormack and Lehane grade, duration of the tracheal intubation and rate
      of successful placement of the ETT in the trachea between TruView EVO2 and McCoy
      laryngoscopes was performed. RESULTS: The results demonstrated that TruView has a
      statistically significant less IDS of 0.33 compared with an IDS of 1.2 for McCoy.
      TruView also had a better Cormack and Lehane glottic view (CL 1 of 77% versus
      40%) and less hemodynamic response. CONCLUSIONS: The TruView blade is a useful
      option for tracheal intubation in patients with suspected cervical spine injury.

PMID- 23162399
TI  - To evaluate the efficacy of intrathecal magnesium sulphate for hysterectomy under
      subarachnoid block with bupivacaine and fentanyl: A prospective randomized double
      blind clinical trial.
AB  - BACKGROUND: Intrathecal magnesium has been found to prolong the duration of
      analgesia in various surgical procedures like lower limb surgeries and as
      adjuncts to general anesthesia for pain management. The present study was
      designed to examine whether addition of intrathecal magnesium sulfate would
      enhance the analgesic efficacy of intrathecal bupivacaine and fentanyl in
      patients undergoing total abdominal hysterectomy. METHODS: After taking informed
      consent, 60 patients were randomised into two groups with 30 patients. Group "S"
      received 2.5 mL (12.5 mg) of hyperbaric bupivacaine + 0.5 mL (25 mcg) of fentanyl
      + 0.5 mL of normal saline and Group "M" received 2.5 mL (12.5 mg) of hyperbaric
      bupivacaine + 0.5 mL (25 mcg) of fentanyl + 0.5 mL (100 mg) of magnesium sulfate.
      Onset of sensory, motor block and duration of analgesia was noted. RESULTS:
      Demographic profile and duration of surgery were comparable (P>0.5). Time of
      onset of sensory and motor blockade was delayed in Group M compared with Group S,
      and this was statistically significant. A statistically significant longer
      duration of analgesia was observed in Group M compared with the control Group S.
      However, the recovery of motor blockade was found to be statistically
      insignificant in both the groups. The hemodynamic parameters were comparable in
      the perioperative period (P>0.05). The incidence of side-effects in both the
      groups were also comparable (P>0.05). CONCLUSION: The addition of 100 mg
      intrathecal magnesium led to prolonged duration of analgesia significantly
      without increasing the incidence of side-effects. Also, there was a significant
      delay in the onset of both sensory and motor blockade.

PMID- 23162400
TI  - Inadvertent endobronchial intubation: A sentinel event.
AB  - BACKGROUND: Unintentional bronchial intubation may result in serious
      complications such as lung collapse or pneumothorax. These complications amount
      to sentinel events should be reported, and a hospital sentinel event policy
      should be implemented, including corrective actions to prevent recurrence.
      METHODS: A 12-month prospective observational study in a multidisciplinary adult
      intensive care unit (ICU) to estimate the frequency of inadvertent bronchial
      intubation and its major sequels in intubated patients admitted to the unit.
      Complications will be reported as sentinel events attracting investigation by
      root cause analysis method, action plan, and follow-up. RESULTS: There were 36
      (12.9%) cases of inadvertent bronchial intubations in 279 orally-intubated
      patients admitted to the ICU during the study period (1.5.2010 - 30.4.2011), 2
      (0.7%) of them already developed total left lung collapse. The hospital sentinel
      event policy was activated followed by action plan, which included raising the
      awareness of the problem, presentations, and regular checking on the position of
      the tube following tracheal intubation at different location in the hospital.
      CONCLUSION: Early detection and correction of endobronchial intubation will
      prevent complications developing. Applying sentinel event policy on complications
      of inadvertent bronchial intubation will encourage finding permanent solution to
      an old and preventable problem. Anesthetic and resuscitative regulatory bodies
      should incorporate methods of checking on correct position of tracheal tubes in
      their training programs. Knowing that the tube may advance into a bronchus, they
      should insist on regular checking of the tube in a manner similar to monitoring
      patient's vital signs.

PMID- 23162401
TI  - Effects of preoperative beta-blocker on blood loss and blood transfusion during
      spinal surgeries with sodium nitroprusside-controlled hypotension.
AB  - BACKGROUND: The present study sought to determine whether premedication with oral
      beta-blocker before hypotensive anesthesia with sodium nitroprusside could
      improve the quality of surgical field, decrease the blood loss, and decrease the
      need for homologous blood transfusion and duration of surgery. METHODS: Eighty
      patients scheduled for spinal fixation surgery were included in a prospective,
      randomized, double-blinded study. Patients were classified into two groups: Group
      I received oral atenolol 50 mg twice one day before surgery; and Group II
      received placebo tablets identical in appearance to atenolol tablets for the same
      period and interval. All patients in both the groups received intraoperative
      sodium nitroprusside (SNP) as a hypotensive agent. Hemodynamic variables, amount
      of sodium nitroprusside used, quality of surgical field, and the amount of
      homologous blood transfusion and blood loss were compared between groups.
      RESULTS: Heart rate and amount of SNP used were significantly less (P<0.0001) in
      the atenolol group, but no significant difference was found in intraoperative
      mean arterial blood pressure (MABP) between the two groups. The time of surgeries
      was significantly shorter in Group I than in Group II (185+/-15.21 vs 225+/-12.61
      min), P<0.0001. The quality of surgical field was better in Group I than in Group
      II in all times of measurements, P<0.0001. The amount of blood loss and the
      amount of packed red blood cells transfused were significantly less in Group I
      than in Group II, P<0.0001. No clinically significant complications were observed
      in either group. CONCLUSION: Premedication with oral atenolol 50 mg twice/day for
      one day before hypotensive anesthesia with SNP during spinal surgeries seems to
      be clinically safe and effective to reduce heart rate, amount of SNP used, amount
      of blood loss, and amount of blood transfused with better quality of surgical
      field.

PMID- 23162402
TI  - Effect of fentanyl versus buprenorphine on the pupil size in phacoemulsification
      cataract surgery.
AB  - BACKGROUND: Despite several recent innovations in phacoemulsification surgery,
      importance of pupil diameter in this surgery is becoming more evident. PURPOSE:
      To compare the effect of opioid agonist (fentanyl) versus opioid agonist
      antagonist (buprenorphine) on pupil diameter in cataract surgery and to choose
      the best opioid in high-risk phacoemulsification surgery. METHODS: In this
      randomized double-blinded clinical trial, 60 patients who were candidates for
      elective phacoemulsification surgery were randomly divided into two equal groups:
      experimental (buprenorphine, 0.3 MUg/kg) and control (fentanyl, 1 MUg/kg). Pupil
      diameter was measured preinjection and at several times postinjection. Blood
      pressure was recorded at several intervals, as well as shivering, nausea and
      vomiting, and recovery time. RESULTS: Mean (SD) recovery time was significantly
      less in the control group (19.46+/-5.43) than in the experimental group (33.23+/
      10.75) (P<0.0001). The constriction effect (ie, pupillary diameter in mm) was
      significantly lower in the experimental group (0.53+/-0.45) than in the control
      group (1.06+/-0.52) (P=0.0001). The percentages of constriction effect in
      experimentaland control groups were 7.68% and 15.07%, respectively. The eye was
      two times more constricted in the control group in comparison with the
      experimental group after induction of anesthesia. CONCLUSION: Buprenorphine is a
      better solution to decrease pupil constriction in comparison with fentanylinhigh
      risk phacoemulsification surgery.

PMID- 23162403
TI  - Evaluation of single epidural bolus dose of magnesium as an adjuvant to epidural
      fentanyl for postoperative analgesia: A prospective, randomized, double-blind
      study.
AB  - OBJECTIVE: Magnesium has been used as an adjuvant by various routes, including
      intravenous, intrathecal, and epidural in different dosage regimens. The effect
      of single bolus dose of magnesium as an adjuvant to fentanyl for postoperative
      analgesia has not been studied. This prospective randomized controlled trial was
      done to evaluate the efficacy of single bolus administration of magnesium
      epidurally as an adjuvant to epidural fentanyl for postoperative analgesia in
      patients undergoing total hip replacement under combined spinal epidural
      anesthesia. METHODS: Sixty patients received combined spinal-epidural anesthesia
      with 2 mL of 0.5% hyperbaric bupivacaine intrathecally. After the surgery,
      patients were randomized into Group F [epidural fentanyl (1 MUg/kg) in 10 mL
      saline] and Group FM [epidural magnesium (75 mg) along with fentanyl (1 MUg/kg)
      in 10 mL saline]. Supplementary analgesia was provided by 50 mg intravenous
      tramadol if Verbal Rating Score (VRS) >4. Patient's first analgesic requirement
      and duration of analgesia were recorded. RESULTS: The duration of analgesia was
      significantly longer for Group FM, 340+/-28.8 min, compared with Group F, 164+/
      17.1 min (P=0.001). The frequency of rescue analgesics required in 24-h
      postoperative period in Group FM (2.3+/-0.5) was significantly less than that in
      Group F (4.3+/-0.5) (P=0.001). VRS was significantly lower in Group FM up to 4 h
      in the postoperative period (P=0.001). Bromage scale was statistically
      insignificant at all points of time. CONCLUSIONS: The administration of magnesium
      (75 mg) as an adjuvant to epidural fentanyl (1 MUg/ kg) for postoperative
      analgesia results in significantly lower VRS with prolonged duration of analgesia
      as compared with epidural fentanyl (1 MUg/kg) alone. Concomitant administration
      of magnesium also reduces the requirement of breakthrough analgesics with no
      increased incidence of side effects.

PMID- 23162404
TI  - Acute epiglottitis: Trends, diagnosis and management.
AB  - Acute epiglottitis is a life-threatening disorder with serious implications to
      the anesthesiologist because of the potential for laryngospasm and irrevocable
      loss of the airway. Acute epiglottitis can occur at any age. Early diagnosis with
      careful and rapid intervention of this serious condition is necessary in order to
      avoid life-threatening complications.

PMID- 23162405
TI  - Obturator neurolysis using 65% alcohol for adductor muscle spasticity.
AB  - Spasticity is motor alteration characterized by muscle hypertonia and
      hyperreflexia. It is an important complication of spinal cord injury, traumatic
      brain injury, cerebral palsy, and multiple sclerosis. If uncorrected, fibrosis
      and eventually bony deformity lock the joint into a fixed contracture. Chemical
      neurolysis using various agents is one of the therapeutic possibilities to
      alleviate spasticity. We are, hereby, reporting 3 patients in whom 65% alcohol
      was used as neurolytic agent for the treatment of hip adductor spasticity, and
      the effect lasted for a variable period.

PMID- 23162406
TI  - Severe hypertension and pulmonary edema associated with systemic absorption of
      topical phenylephrine in a child during retinal surgery.
AB  - Topical phenylephrine solutions are widely used in eye procedures to promote
      pupil dilation without cycloplegia. We report a case of intraoperative severe
      hypertension and acute pulmonary edema occurring in a child during retinal
      surgery after possible systemic absorption of topical phenylephrine eyedrops. Our
      objective is to discuss the proper treatment and preventive strategies for such a
      complication. A 4-year-old, male patient, 18.4 kg in weight, physical status ASA
      I was admitted for right retinal detachment surgery. Anesthesia was induced with
      sevoflurane in oxygen, followed by glycopyrrolate (5.0 MUg/kg), propofol 25 mg,
      fentanyl 50 MUg and cisatracurium 0.15 mg/kg given intravenously. Anesthesia was
      maintained with sevoflurane 2-2.5% in a mixture of nitrous oxide and oxygen
      (60%:40%). After incision, two drops of 10% aqueous phenylephrine were
      administered topically by the surgeon to the right eye for further pupil
      dilation. Few minutes later, the noninvasive blood pressure rose to 220/120 mmHg
      and the heart rate increased to 140 beats/min. Oxygen saturation (SpO(2)) dropped
      from 99% (with an inspired oxygen concentration (FiO(2)) of 0.4) to 82%.
      Auscultation revealed crepitations throughout the chest and a blood-stained
      frothy fluid was aspirated from the trachea with possible development of acute
      pulmonary edema. Hydralazine (5 mg) and furosemide (10 mg) were administered
      intravenously. Seven minutes later, the blood pressure returned to normal and the
      SpO(2) increased to 92% on FiO(2) of 1.0, with decreased intratracheal
      secretions. After approximately 20 minutes, the SpO(2) had improved to 99%, with
      a FiO(2) of 1.0 and the blood pressure was 109/63 mmHg and heart rate was 121
      beats/min. The FiO(2) gradually reduced back to 0.4 over 30 min with no further
      desaturation. The patient was discharged from the post anesthesia care unit 5 h
      after surgery with adequate spontaneous breathing, SpO(2) 99% on room air, normal
      blood pressure and pulmonary auscultation. Anesthesiologists and ophthalmologists
      should be aware of the possible cardiovascular side-effects of topical
      phenylephrine, and it should be used cautiously with appropriate intraoperative
      monitoring of hemodynamic variables. Moreover, preventive strategies to minimize
      systemic absorption of the drug should be taken.

PMID- 23162407
TI  - Perioperative management of a patient with Gilberts syndrome and rheumatic heart
      disease.
AB  - Anaesthetic management of patients with hepatic dysfunction can be quite
      challenging, as many anaesthetic agents are metabolized by liver. Heart disease
      on anti coagulation can pose additional challenge. Here we report a case of
      Gilbert's syndrome with rheumatic heart disease on anti coagulation posted for
      elective hernia repair.

PMID- 23162408
TI  - Wire-guided (Seldinger technique) intubation through a face mask in urgent,
      difficult and grossly distorted airways.
AB  - We report two cases of successful urgent intubation using a Seldinger technique
      for airway management through an anesthesia facemask, while maintaining
      ventilation in patients with difficult airways and grossly distorted airway
      anatomy. In both cases, conventional airway management techniques were predicted
      to be difficult or impossible, and a high likelihood for a surgical airway was
      present. This technique was chosen as it allows tracheal tube placement through
      the nares during spontaneous ventilation with the airway stented open and oxygen
      delivery with either continuous positive airway pressure and/or pressure support
      ventilation. This unhurried technique may allow intubation when other techniques
      are unsuitable, while maintaining control of the airway.

PMID- 23162409
TI  - Acute unilateral parotid gland swelling after lateral decubitus position under
      general anesthesia.
AB  - Acute swelling of the parotid gland after general anesthesia (commonly known as
      anesthesia mumps or acute postoperative sialadenitis) is a rare but declared
      complication of anesthesia. The etiology is not clear, but some possible causes
      such as obstruction of glandular excretory ducts caused by patient position and
      increase in the viscosity of the saliva because of acute dehydratation and/or
      medications like atropin have been proposed. We report a swelling in the left
      preauricular and postauricular region extending to the angle of the mandibule in
      a 35-year-old patient after left lateral decubitus position for laparoscopic
      nephrectomy.

PMID- 23162410
TI  - Child with aplastic anemia: Anesthetic management.
AB  - Aplastic anemia is a rare heterogeneous disorder of hematopoietic stem cells
      causing pancytopenia and marrow hypoplasia with the depletion of all types of
      blood cells. This results in anemia, neutropenia and thrombocytopenia, which pose
      a challenge to both surgical and anesthetic management of such cases. We report a
      child with aplastic anemia who sustained traumatic ulcer on the arm and underwent
      split-thickness skin grafting under general anesthesia. There are only two case
      reports on anesthetic considerations in aplastic anemia patients in the
      literature. The anesthetic management is challenging because of the rarity of the
      disease, associated pancytopenia and immunosuppression.

PMID- 23162411
TI  - Laparoscopic cholecystectomy in a patient with Ebstein's anomaly: Anesthetic
      considerations.

PMID- 23162412
TI  - Upper limb weakness following lumber disc surgery: An unusual case.

PMID- 23162413
TI  - Etomidate induced agitation during intraoperative sedation.

PMID- 23162414
TI  - Airway emergency post thyroidectomy: the role of thyroid hormone pharmacokinetics
      and compliance with treatment.

PMID- 23162415
TI  - Anesthetic challenges during perioperative management of patient undergoing
      repair of basal encephalocele with cleft palate.

PMID- 23162416
TI  - Severe bradycardia during laryngoscopy in adult neurosurgical patient.

PMID- 23162417
TI  - Conjunctival injury due to intra venous cannula.

PMID- 23162418
TI  - Increasing the margin of safety during fiberoptic-guided intubation: Use of a jet
      ventilator.

PMID- 23162419
TI  - Indigenous drug delivery system for use in nerve blocks.

PMID- 23162420
TI  - An easy solution to obstructed sampling line: Auxillary oxygen flowmeter.

PMID- 23162421
TI  - Cumulative effect in transfusion related acute lung injury.

PMID- 23162422
TI  - An improvised indigenous technique for nerve stimulation-assisted peripheral
      nerve blocks.
AB  - Regional anesthesia is one of the most satisfying expertise in anesthesia. Nerve
      stimulation guided peripheral nerve blocks greatly enhance the success rate of
      block. Often the nerve stimulation needle becomes a limiting factor due to cost
      and unavailablity. We have proposed a simple innovation to create a nerve
      stimulation needle at the point of care that would overcome the limitation
      associated with commercially available needle for nerve stimulation. This
      innovation may prove instrumental in training of anesthesia residents at no
      extracost to the patient.

PMID- 23162423
TI  - Mean Expression of the X-Chromosome is Associated with Neuronal Density.
AB  - BACKGROUND: Neurodegenerative diseases are characterized by key features such as
      loss of neurons, astrocytosis, and microglial activation/proliferation. These
      changes cause differences in the density of cell types between control and
      disease subjects, confounding results from gene expression studies. Chromosome X
      (ChrX) is known to be specifically important in the brain. We hypothesized the
      existence of a chromosomal signature of gene expression associated with the X
      chromosome for neurological conditions not normally associated with that
      chromosome. The hypothesis was investigated using publicly available microarray
      datasets from studies on Parkinson's disease, Alzheimer's disease, and
      Huntington's disease. Data were analyzed using Chromowave, an analytical tool for
      detecting spatially extended expression changes along chromosomes. To examine
      associations with neuronal density and astrocytosis, the expression of cell
      specific reporter genes was extracted. The association between these genes and
      the expression patterns extracted by Chromowave was then analyzed. Further
      analyses of the X:Autosome ratios for laser dissected neurons, microglia cultures
      and whole tissue were performed to detect cell specific differences. RESULTS: We
      observed an extended pattern of low expression of ChrX consistent in all the
      neurodegenerative disease brain datasets. There was a strong correlation between
      mean ChrX expression and the pattern extracted from the autosomal genes
      representing neurons, but not with mean autosomal expression. No chromosomal
      patterns associated with the neuron specific genes were found on other
      chromosomes. The chromosomal expression pattern was not present in datasets from
      blood cells. The X:Autosome expression ratio was also higher in neuronal cells
      than in tissues with a mix of cell types. CONCLUSIONS: The results suggest that
      neurological disorders show as a reduction in mean expression of many genes along
      ChrX. The most likely explanation for this finding relates to the documented
      general up-regulation of ChrX in brain tissue which, this work suggests, occurs
      primarily in neurons. If validated, this cell specific ChrX expression warrants
      further research as understanding the biological reasons and mechanisms for this
      expression, may help to elucidate a connection with the development of
      neurodegenerative disorders.

PMID- 23162424
TI  - Effects of Prior Knowledge on Decisions Made Under Perceptual vs. Categorical
      Uncertainty.
AB  - Humans use prior knowledge to bias decisions made under uncertainty. In this fMRI
      study we predicted that different brain dynamics play a role when prior knowledge
      is added to decisions made under perceptual vs. categorical uncertainty. Subjects
      decided whether shapes belonged to Category S - smoother - or Category B -
      bumpier - under both uncertainty conditions, with or without prior knowledge
      cues. When present, the prior knowledge cue, 80/20 or 50/50, indicated that 80
      and 20% (or 50 and 50%) were the chances that responding "S" and "B" (or vice
      versa) would be correct. During perceptual uncertainty, shapes were degraded with
      noise. During categorical uncertainty, shapes were ambiguous. Adding the 80/20
      cue increased activation during perceptual uncertainty in bilateral lateral
      occipital (LO) cortex and left middle frontal gyrus (MidFG), and decreased
      activity in bilateral LO cortex during categorical uncertainty. Right MidFG and
      other frontoparietal regions were active in all conditions. The results
      demonstrate that left MidFG shows activation changes, suggestive of an influence
      on visual cortex, that depend on the factor that makes the decisions difficult.
      When sensory evidence is difficult to perceive, prior knowledge increases visual
      cortical activity. When the sensory evidence is easy to perceive but difficult to
      interpret, prior knowledge decreases visual cortical activity.

PMID- 23162425
TI  - Unsupervised adaptation of brain-machine interface decoders.
AB  - The performance of neural decoders can degrade over time due to non
      stationarities in the relationship between neuronal activity and behavior. In
      this case, brain-machine interfaces (BMI) require adaptation of their decoders to
      maintain high performance across time. One way to achieve this is by use of
      periodical calibration phases, during which the BMI system (or an external human
      demonstrator) instructs the user to perform certain movements or behaviors. This
      approach has two disadvantages: (i) calibration phases interrupt the autonomous
      operation of the BMI and (ii) between two calibration phases the BMI performance
      might not be stable but continuously decrease. A better alternative would be that
      the BMI decoder is able to continuously adapt in an unsupervised manner during
      autonomous BMI operation, i.e., without knowing the movement intentions of the
      user. In the present article, we present an efficient method for such
      unsupervised training of BMI systems for continuous movement control. The
      proposed method utilizes a cost function derived from neuronal recordings, which
      guides a learning algorithm to evaluate the decoding parameters. We verify the
      performance of our adaptive method by simulating a BMI user with an optimal
      feedback control model and its interaction with our adaptive BMI decoder. The
      simulation results show that the cost function and the algorithm yield fast and
      precise trajectories toward targets at random orientations on a 2-dimensional
      computer screen. For initially unknown and non-stationary tuning parameters, our
      unsupervised method is still able to generate precise trajectories and to keep
      its performance stable in the long term. The algorithm can optionally work also
      with neuronal error-signals instead or in conjunction with the proposed
      unsupervised adaptation.

PMID- 23162426
TI  - Inhibitory control of hippocampal inhibitory neurons.
AB  - Information processing within neuronal networks is determined by a dynamic
      partnership between principal neurons and local circuit inhibitory interneurons.
      The population of GABAergic interneurons is extremely heterogeneous and
      comprises, in many brain regions, cells with divergent morphological and
      physiological properties, distinct molecular expression profiles, and highly
      specialized functions. GABAergic interneurons have been studied extensively
      during the past two decades, especially in the hippocampus, which is a relatively
      simple cortical structure. Different types of hippocampal inhibitory interneurons
      control spike initiation [e.g., axo-axonic and basket cells (BCs)] and synaptic
      integration (e.g., bistratified and oriens-lacunosum moleculare interneurons)
      within pyramidal neurons and synchronize local network activity, providing a
      means for functional segregation of neuronal ensembles and proper routing of
      hippocampal information. Thus, it is thought that, at least in the hippocampus,
      GABAergic inhibitory interneurons represent critical regulating elements at all
      stages of information processing, from synaptic integration and spike generation
      to large-scale network activity. However, this raises an important question: if
      inhibitory interneurons are fundamental for network computations, what are the
      mechanisms that control the activity of the interneurons themselves? Given the
      essential role of synaptic inhibition in the regulation of neuronal activity, it
      would be logical to expect that specific inhibitory mechanisms have evolved to
      control the operation of interneurons. Here, we review the mechanisms of synaptic
      inhibition of interneurons and discuss their role in the operation of hippocampal
      inhibitory circuits.

PMID- 23162428
TI  - The Yin and Yen of GABA in Brain Development and Operation in Health and Disease.

PMID- 23162430
TI  - Enriching the environment to disinhibit the brain and improve cognition.

PMID- 23162427
TI  - Neuroplasticity in addiction: cellular and transcriptional perspectives.
AB  - Drug addiction is a chronic, relapsing brain disorder which consists of
      compulsive patterns of drug-seeking and taking that occurs at the expense of
      other activities. The transition from casual to compulsive drug use and the
      enduring propensity to relapse is thought to be underpinned by long-lasting
      neuroadaptations in specific brain circuitry, analogous to those that underlie
      long-term memory formation. Research spanning the last two decades has made great
      progress in identifying cellular and molecular mechanisms that contribute to drug
      induced changes in plasticity and behavior. Alterations in synaptic transmission
      within the mesocorticolimbic and corticostriatal pathways, and changes in the
      transcriptional potential of cells by epigenetic mechanisms are two important
      means by which drugs of abuse can induce lasting changes in behavior. In this
      review we provide a summary of more recent research that has furthered our
      understanding of drug-induced neuroplastic changes both at the level of the
      synapse, and on a transcriptional level, and how these changes may relate to the
      human disease of addiction.

PMID- 23162429
TI  - Species-dependent differences of embryonic stem cell-derived neural stem cells
      after Interferon gamma treatment.
AB  - Pluripotent stem cell (pSC)-derived, neural stem cells (NSCs) are actually
      extensively explored in the field of neuroregeneration and to clarify disease
      mechanisms or model neurological diseases in vitro. Regarding the latter,
      proliferation and differentiation of pSC-derived NSCs are investigated under the
      influence of a variety of different substances among them key players of
      inflammation. However, results generated on a murine genetic background are not
      always representative for the human situation which increasingly leads to the
      application of human cell culture systems derived from human pSCs. We
      investigated here, if the recently described interferon gamma (IFNgamma)-induced
      dysregulated neural phenotype characterized by simultaneous expression of glial
      and neuronal markers on murine NSCs (Walter et al., 2011, 2012) can also be found
      on a human genetic background. For this purpose, we performed experiments with
      human embryonic stem cell-derived NSCs. We could show that the IFNgamma-induced
      dysregulated neural phenotype cannot be induced in human NSCs. This difference
      occurs, although typical genes like signal transducers and activators of
      transcription 1 (Stat 1) or interferon regulatory factor 9 (IRF-9) are similarly
      regulated by IFNgamma in both, murine and human populations. These results
      illustrate that fundamental differences between murine and human neural
      populations exist in vitro, independent of anatomical system-related properties.

PMID- 23162431
TI  - Temporal response dynamics of Drosophila olfactory sensory neurons depends on
      receptor type and response polarity.
AB  - Insect olfactory sensory neurons (OSN) express a diverse array of receptors from
      different protein families, i.e. ionotropic receptors (IR), gustatory receptors
      (GR) and odorant receptors (OR). It is well known that insects are exposed to a
      plethora of odor molecules that vary widely in both space and time under
      turbulent natural conditions. In addition to divergent ligand specificities,
      these different receptors might also provide an increased range of temporal
      dynamics and sensitivities for the olfactory system. To test this, we challenged
      different Drosophila OSNs with both varying stimulus durations (10-2000 ms), and
      repeated stimulus pulses of key ligands at various frequencies (1-10 Hz). Our
      results show that OR-expressing OSNs responded faster and with higher sensitivity
      to short stimulations as compared to IR- and Gr21a-expressing OSNs. In addition,
      OR-expressing OSNs could respond to repeated stimulations of excitatory ligands
      up to 5 Hz, while IR-expressing OSNs required ~5x longer stimulations and/or
      higher concentrations to respond to similar stimulus durations and frequencies.
      Nevertheless, IR-expressing OSNs did not exhibit adaptation to longer
      stimulations, unlike OR- and Gr21a-OSNs. Both OR- and IR-expressing OSNs were
      also unable to resolve repeated pulses of inhibitory ligands as fast as
      excitatory ligands. These differences were independent of the peri-receptor
      environment in which the receptors were expressed and suggest that the receptor
      expressed by a given OSN affects both its sensitivity and its response to
      transient, intermittent chemical stimuli. OR-expressing OSNs are better at
      resolving low dose, intermittent stimuli, while IR-expressing OSNs respond more
      accurately to long-lasting odor pulses. This diversity increases the capacity of
      the insect olfactory system to respond to the diverse spatiotemporal signals in
      the natural environment.

PMID- 23162432
TI  - Large-scale, high-resolution electrophysiological imaging of field potentials in
      brain slices with microelectronic multielectrode arrays.
AB  - Multielectrode arrays (MEAs) are extensively used for electrophysiological
      studies on brain slices, but the spatial resolution and field of recording of
      conventional arrays are limited by the low number of electrodes available. Here,
      we present a large-scale array recording simultaneously from 4096 electrodes used
      to study propagating spontaneous and evoked network activity in acute murine
      cortico-hippocampal brain slices at unprecedented spatial and temporal
      resolution. We demonstrate that multiple chemically induced epileptiform episodes
      in the mouse cortex and hippocampus can be classified according to their spatio
      temporal dynamics. Additionally, the large-scale and high-density features of our
      recording system enable the topological localization and quantification of the
      effects of antiepileptic drugs in local neuronal microcircuits, based on the
      distinct field potential propagation patterns. This novel high-resolution
      approach paves the way to detailed electrophysiological studies in brain circuits
      spanning spatial scales from single neurons up to the entire slice network.

PMID- 23162433
TI  - Toward a full-scale computational model of the rat dentate gyrus.
AB  - Recent advances in parallel computing, including the creation of the parallel
      version of the NEURON simulation environment, have allowed for a previously
      unattainable level of complexity and detail in neural network models. Previously,
      we published a functional NEURON model of the rat dentate gyrus with over 50,000
      biophysically realistic, multicompartmental neurons, but network simulations
      could only utilize a single processor. By converting the model to take advantage
      of parallel NEURON, we are now able to utilize greater computational resources
      and are able to simulate the full-scale dentate gyrus, containing over a million
      neurons. This has eliminated the previous necessity for scaling adjustments and
      allowed for a more direct comparison to experimental techniques and results. The
      translation to parallel computing has provided a superlinear speedup of
      computation time and dramatically increased the overall computer memory available
      to the model. The incorporation of additional computational resources has allowed
      for more detail and elements to be included in the model, bringing the model
      closer to a more complete and accurate representation of the biological dentate
      gyrus. As an example of a major step toward an increasingly accurate
      representation of the biological dentate gyrus, we discuss the incorporation of
      realistic granule cell dendrites into the model. Our previous model contained
      simplified, two-dimensional dendritic morphologies that were identical for
      neurons of the same class. Using the software tools L-Neuron and L-Measure, we
      are able to introduce cell-to-cell variability by generating detailed, three
      dimensional granule cell morphologies that are based on biological
      reconstructions. Through these and other improvements, we aim to construct a more
      complete full-scale model of the rat dentate gyrus, to provide a better tool to
      delineate the functional role of cell types within the dentate gyrus and their
      pathological changes observed in epilepsy.

PMID- 23162434
TI  - Connectivity from OR37 expressing olfactory sensory neurons to distinct cell
      types in the hypothalamus.
AB  - Olfactory sensory neurons (OSNs) which express a member from the OR37 subfamily
      of odorant receptor (OR) genes are wired to the main olfactory bulb (MOB) in a
      unique monoglomerular fashion; from these glomeruli an untypical connectivity
      into higher brain centers exists. In the present study we have investigated by
      DiI and transsynaptic tracing approaches how the connection pattern from these
      glomeruli into distinct hypothalamic nuclei is organized. The application of DiI
      onto the ventral domain of the bulb which harbors the OR37 glomeruli resulted in
      the labeling of fibers within the paraventricular nucleus (PVN) and supraoptic
      nucleus (SO) of the hypothalamus; some of these fibers were covered with varicose
      like structures. No DiI-labeled cell somata were detectable in these nuclei. The
      data indicate that projection neurons which originate in the OR37 region of the
      MOB form direct connections into these nuclei. The cells that were labeled by the
      transsynaptic tracer WGA in these nuclei were further characterized. Their
      distribution pattern in the paraventricular nucleus was reminiscent of cells
      which produce distinct neuropeptides. Double labeling experiments confirmed that
      they contained vasopressin, but not the related neuropeptide oxytocin.
      Morphological analysis revealed that they comprise of magno- and parvocellular
      cells. A comparative investigation of the WGA-positive cells in the SO
      demonstrated that these were vasopressin-positive, as well, whereas oxytocin
      producing cells of this nucleus also contained no transsynaptic tracer. Together,
      the data demonstrates a connectivity from OR37 expressing sensory neurons to
      distinct hypothalamic neurons with the same neuropeptide content.

PMID- 23162435
TI  - Competition from newborn granule cells does not drive axonal retraction of
      silenced old granule cells in the adult hippocampus.
AB  - In the developing nervous system synaptic refinement, typified by the
      neuromuscular junction where supernumerary connections are eliminated by axon
      retraction leaving the postsynaptic target innervated by a single dominant input,
      critically regulates neuronal circuit formation. Whether such competition-based
      pruning continues in established circuits of mature animals remains unknown. This
      question is particularly relevant in the context of adult neurogenesis where
      newborn cells must integrate into preexisting circuits, and thus, potentially
      compete with functionally mature synapses to gain access to their postsynaptic
      targets. The hippocampus plays an important role in memory formation/retrieval
      and the dentate gyrus (DG) subfield exhibits continued neurogenesis into
      adulthood. Therefore, this region contains both mature granule cells (old GCs)
      and immature recently born GCs that are generated throughout adult life (young
      GCs), providing a neurogenic niche model to examine the role of competition in
      synaptic refinement. Recent work from an independent group in developing animals
      indicated that embryonically/early postnatal generated GCs placed at a
      competitive disadvantage by selective expression of tetanus toxin (TeTX) to
      prevent synaptic release rapidly retracted their axons, and that this retraction
      was driven by competition from newborn GCs lacking TeTX. In contrast, following 3
      6 months of selective TeTX expression in old GCs of adult mice we did not observe
      any evidence of axon retraction. Indeed ultrastructural analyses indicated that
      the terminals of silenced GCs even maintained synaptic contact with their
      postsynaptic targets. Furthermore, we did not detect any significant differences
      in the electrophysiological properties between old GCs in control and TeTX
      conditions. Thus, our data demonstrate a remarkable stability in the face of a
      relatively prolonged period of altered synaptic competition between two
      populations of neurons within the adult brain.

PMID- 23162436
TI  - Coupling BCI and cortical stimulation for brain-state-dependent stimulation:
      methods for spectral estimation in the presence of stimulation after-effects.
AB  - Brain-state-dependent stimulation (BSDS) combines brain-computer interfaces
      (BCIs) and cortical stimulation into one paradigm that allows the online decoding
      for example of movement intention from brain signals while simultaneously
      applying stimulation. If the BCI decoding is performed by spectral features,
      stimulation after-effects such as artefacts and evoked activity present a
      challenge for a successful implementation of BSDS because they can impair the
      detection of targeted brain states. Therefore, efficient and robust methods are
      needed to minimize the influence of the stimulation-induced effects on spectral
      estimation without violating the real-time constraints of the BCI. In this work,
      we compared four methods for spectral estimation with autoregressive (AR) models
      in the presence of pulsed cortical stimulation. Using combined EEG-TMS
      (electroencephalography-transcranial magnetic stimulation) as well as combined
      electrocorticography (ECoG) and epidural electrical stimulation, three patients
      performed a motor task using a sensorimotor-rhythm BCI. Three stimulation
      paradigms were varied between sessions: (1) no stimulation, (2) single
      stimulation pulses applied independently (open-loop), or (3) coupled to the BCI
      output (closed-loop) such that stimulation was given only while an intention to
      move was detected using neural data. We found that removing the stimulation after
      effects by linear interpolation can introduce a bias in the estimation of the
      spectral power of the sensorimotor rhythm, leading to an overestimation of
      decoding performance in the closed-loop setting. We propose the use of the Burg
      algorithm for segmented data to deal with stimulation after-effects. This work
      shows that the combination of BCIs controlled with spectral features and cortical
      stimulation in a closed-loop fashion is possible when the influence of
      stimulation after-effects on spectral estimation is minimized.

PMID- 23162437
TI  - Hypothalamus-olfactory system crosstalk: orexin a immunostaining in mice.
AB  - It is well known that olfaction influences food intake, and conversely, that an
      individual's nutritional status modulates olfactory sensitivity. However, what is
      still poorly understood is the neuronal correlate of this relationship, as well
      as the connections between the olfactory bulb and the hypothalamus. The goal of
      this report is to analyze the relationship between the olfactory bulb and
      hypothalamus, focusing on orexin A immunostaining, a hypothalamic neuropeptide
      that is thought to play a role in states of sleep/wakefulness. Interestingly,
      orexin A has also been described as a food intake stimulator. Such an effect may
      be due in part to the stimulation of the olfactory bulbar pathway. In rats,
      orexin positive cells are concentrated strictly in the lateral hypothalamus,
      while their projections invade nearly the entire brain including the olfactory
      system. Therefore, orexin appears to be a good candidate to play a pivotal role
      in connecting olfactory and hypothalamic pathways. So far, orexin has been
      described in rats, however, there is still a lack of information concerning its
      expression in the brains of adult and developing mice. In this context, we
      revisited the orexin A pattern in adult and developing mice using
      immunohistological methods and confocal microscopy. Besides minor differences,
      orexin A immunostaining in mice shares many features with those observed in rats.
      In the olfactory bulb, even though there are few orexin projections, they reach
      all the different layers of the olfactory bulb. In contrast to the presence of
      orexin projections in the main olfactory bulb, almost none have been found in the
      accessory olfactory bulb. The developmental expression of orexin A supports the
      hypothesis that orexin expression only appears post-natally.

PMID- 23162439
TI  - Kernel Principal Component Analysis for dimensionality reduction in fMRI-based
      diagnosis of ADHD.
AB  - This study explored various feature extraction methods for use in automated
      diagnosis of Attention-Deficit Hyperactivity Disorder (ADHD) from functional
      Magnetic Resonance Image (fMRI) data. Each participant's data consisted of a
      resting state fMRI scan as well as phenotypic data (age, gender, handedness, IQ,
      and site of scanning) from the ADHD-200 dataset. We used machine learning
      techniques to produce support vector machine (SVM) classifiers that attempted to
      differentiate between (1) all ADHD patients vs. healthy controls and (2) ADHD
      combined (ADHD-c) type vs. ADHD inattentive (ADHD-i) type vs. controls. In
      different tests, we used only the phenotypic data, only the imaging data, or else
      both the phenotypic and imaging data. For feature extraction on fMRI data, we
      tested the Fast Fourier Transform (FFT), different variants of Principal
      Component Analysis (PCA), and combinations of FFT and PCA. PCA variants included
      PCA over time (PCA-t), PCA over space and time (PCA-st), and kernelized PCA (kPCA
      st). Baseline chance accuracy was 64.2% produced by guessing healthy control (the
      majority class) for all participants. Using only phenotypic data produced 72.9%
      accuracy on two class diagnosis and 66.8% on three class diagnosis. Diagnosis
      using only imaging data did not perform as well as phenotypic-only approaches.
      Using both phenotypic and imaging data with combined FFT and kPCA-st feature
      extraction yielded accuracies of 76.0% on two class diagnosis and 68.6% on three
      class diagnosis-better than phenotypic-only approaches. Our results demonstrate
      the potential of using FFT and kPCA-st with resting-state fMRI data as well as
      phenotypic data for automated diagnosis of ADHD. These results are encouraging
      given known challenges of learning ADHD diagnostic classifiers using the ADHD-200
      dataset (see Brown et al., 2012).

PMID- 23162438
TI  - One nose, one brain: contribution of the main and accessory olfactory system to
      chemosensation.
AB  - The accessory olfactory system is present in most tetrapods. It is involved in
      the perception of chemical stimuli, being implicated also in the detection of
      pheromones. However, it is sensitive also to some common odorant molecules, which
      have no clear implication in intraspecific chemical communication. The accessory
      olfactory system may complement the main olfactory system and may contribute
      different perceptual features to the construction of a unitary representation,
      which merges the different chemosensory qualities. Crosstalk between the main and
      accessory olfactory systems occurs at different levels of central processing, in
      brain areas where the inputs from the two systems converge. Interestingly,
      centrifugal projections from more caudal brain areas are deeply involved in
      modulating both main and accessory sensory processing. A high degree of
      interaction between the two systems may be conceived and partial overlapping
      appears to occur in many functions. Therefore, the central chemosensory
      projections merge inputs from different organs to obtain a complex chemosensory
      picture.

PMID- 23162440
TI  - Exploiting the brain's network structure in identifying ADHD subjects.
AB  - Attention Deficit Hyperactive Disorder (ADHD) is a common behavioral problem
      affecting children. In this work, we investigate the automatic classification of
      ADHD subjects using the resting state functional magnetic resonance imaging
      (fMRI) sequences of the brain. We show that brain can be modeled as a functional
      network, and certain properties of the networks differ in ADHD subjects from
      control subjects. We compute the pairwise correlation of brain voxels' activity
      over the time frame of the experimental protocol which helps to model the
      function of a brain as a network. Different network features are computed for
      each of the voxels constructing the network. The concatenation of the network
      features of all the voxels in a brain serves as the feature vector. Feature
      vectors from a set of subjects are then used to train a PCA-LDA (principal
      component analysis-linear discriminant analysis) based classifier. We
      hypothesized that ADHD related differences lie in some specific regions of brain
      and using features only from those regions are sufficient to discriminate ADHD
      and control subjects. We propose a method to create a brain mask which includes
      the useful regions only and demonstrate that using the feature from the masked
      regions improves classification accuracy on the test data set. We train our
      classifier with 776 subjects, and test on 171 subjects provided by the Neuro
      Bureau for the ADHD-200 challenge. We demonstrate the utility of graph-motif
      features, specifically the maps that represent the frequency of participation of
      voxels in network cycles of length 3. The best classification performance
      (69.59%) is achieved using 3-cycle map features with masking. Our proposed
      approach holds promise in being able to diagnose and understand the disorder.

PMID- 23162441
TI  - Combined laryngeal inflammation and trauma mediate long-lasting immunoreactivity
      response in the brainstem sensory nuclei in the rat.
AB  - Somatosensory feedback from the larynx plays a critical role in regulation of
      normal upper airway functions, such as breathing, deglutition, and voice
      production, while altered laryngeal sensory feedback is known to elicit a variety
      of pathological reflex responses, including persistent coughing, dysphonia, and
      laryngospasm. Despite its clinical impact, the central mechanisms underlying the
      development of pathological laryngeal responses remain poorly understood. We
      examined the effects of persistent vocal fold (VF) inflammation and trauma, as
      frequent causes of long-lasting modulation of laryngeal sensory feedback, on
      brainstem immunoreactivity in the rat. Combined VF inflammation and trauma were
      induced by injection of lipopolysaccharide (LPS) solution and compared to VF
      trauma alone from injection of vehicle solution and to controls without any VF
      manipulations. Using a c-fos marker, we found significantly increased Fos-like
      immunoreactivity (FLI) in the bilateral intermediate/parvicellular reticular
      formation (IRF/PCRF) with a trend in the left solitary tract nucleus (NTS) only
      in animals with combined LPS-induced VF inflammation and trauma. Further, FLI in
      the right NTS was significantly correlated with the severity of LPS-induced VF
      changes. However, increased brainstem FLI response was not associated with FLI
      changes in the first-order neurons of the laryngeal afferents located in the
      nodose and jugular ganglia in either group. Our data indicate that complex VF
      alterations (i.e., inflammation/trauma vs. trauma alone) may cause prolonged
      excitability of the brainstem nuclei receiving a direct sensory input from the
      larynx, which, in turn, may lead to (mal)plastic changes within the laryngeal
      central sensory control.

PMID- 23162442
TI  - A closer look at visually guided saccades in autism and Asperger's disorder.
AB  - Motor impairments have been found to be a significant clinical feature associated
      with autism and Asperger's disorder (AD) in addition to core symptoms of
      communication and social cognition deficits. Motor deficits in high-functioning
      autism (HFA) and AD may differentiate these disorders, particularly with respect
      to the role of the cerebellum in motor functioning. Current neuroimaging and
      behavioral evidence suggests greater disruption of the cerebellum in HFA than AD.
      Investigations of ocular motor functioning have previously been used in clinical
      populations to assess the integrity of the cerebellar networks, through
      examination of saccade accuracy and the integrity of saccade dynamics. Previous
      investigations of visually guided saccades in HFA and AD have only assessed basic
      saccade metrics, such as latency, amplitude, and gain, as well as peak velocity.
      We used a simple visually guided saccade paradigm to further characterize the
      profile of visually guided saccade metrics and dynamics in HFA and AD. It was
      found that children with HFA, but not AD, were more inaccurate across both small
      (5 degrees ) and large (10 degrees ) target amplitudes, and final eye position
      was hypometric at 10 degrees . These findings suggest greater functional
      disturbance of the cerebellum in HFA than AD, and suggest fundamental
      difficulties with visual error monitoring in HFA.

PMID- 23162444
TI  - Modulation of early and late event-related potentials by emotion.
AB  - Although emotionally salient stimuli influence higher order information
      processing, the relative vulnerability of specific stages of cognitive processing
      to modulation by emotional input remains elusive. To test the temporal dynamics
      of emotional interference during executive function, we recorded event-related
      potentials (ERPs) while participants performed an effortful anticipation task
      with aversive emotional and neutral distracters. Participants were presented with
      a modified delayed Stroop task that dissociated the anticipation of an easier or
      more difficult task (instructional cues to attend to word vs. color) from the
      response to the Stroop stimulus, while aversive and neutral pictures were
      displayed during the delay period. Our results indicated a relative decrease in
      the amplitude of the contingent negative variation (CNV) during aversive trials
      that was greater during the early anticipatory phase than during the later
      response preparation phase, and greater during (the more difficult) color than
      word trials. During the initial stage of cue processing, there was also
      significant interaction between emotion and anticipatory difficulty on N1
      amplitude, where emotional stimuli led to significantly enhanced negativity
      during color cues relative to word cues. These results suggest that earlier
      processes of orientation and effortful anticipation may reflect executive
      engagement that is influenced by emotional interference while later phases of
      response preparation may be modulated by emotional interference regardless of
      anticipatory difficulty.

PMID- 23162446
TI  - An exploration of sensory and movement differences from the perspective of
      individuals with autism.
AB  - Parents, teachers, and people who themselves experience sensory and movement
      differences have consistently reported disturbances of sensation and movement
      associated with autism. Our review of the literature has revealed both historical
      and recent references to and research about sensory and movement difference
      characteristics and symptoms for individuals with autism. What is notably
      infrequent in this literature, however, is research that highlights the
      perspective of the individual with autism. If we wish to truly understand the
      experience of sensory and movement differences for individuals with autism, we
      must explore their experiences and perspectives. This study presents a
      qualitative analysis of more than 40 h in-depth inquiry into the lives of five
      individuals with the autism label. Data were sorted into six categories:
      perception, action, posture, emotion, communication, and cognition. The insights
      into sensory and movement differences and autism offered by these individuals was
      illuminating. We found that the data strongly supported the presence of
      disruption of organization and regulation of sensory and movement differences in
      the lived experience of these participants with autism. The present data suggests
      that in autism this disruption of organization and regulation is amplified in
      terms of quantity, quality, intensity, and may affect everyday life. These data
      contribute to a more expansive view of autism that incorporates the possibility
      that autism is a disorder that affects motor planning, behavior, communication,
      the sensory motor system, and the dynamic interaction of all of these.

PMID- 23162445
TI  - A possible role of the locus coeruleus in complex regional pain syndrome.
AB  - Heightened sensitivity to painful stimulation commonly spreads from the affected
      limb to the ipsilateral forehead in patients with complex regional pain syndrome
      (CRPS). In addition, acoustic startle evokes greater auditory discomfort and
      increases in limb pain when presented on the affected than unaffected side. In
      contrast, limb pain ordinarily evokes analgesia in the ipsilateral forehead of
      healthy participants, and acoustic startle suppresses limb pain. Together, these
      findings suggest that hemilateral and generalized pain control mechanisms are
      disrupted in CRPS, and that multisensory integrative processes are compromised.
      Failure to inhibit nociceptive input from the CRPS-affected limb could sensitize
      spinal and supraspinal neurons that receive convergent nociceptive and auditory
      information from hemilateral body sites. Somatosensory, auditory, and emotional
      inputs may then aggravate pain by feeding into this sensitized nociceptive
      network. In particular, a disturbance in hemilateral pain processing that
      involves the locus coeruleus could exacerbate the symptoms of CRPS in some
      patients.

PMID- 23162447
TI  - Emotion potentiates response activation and inhibition in masked priming.
AB  - Previous studies have shown that emotion can have 2-fold effects on perception.
      At the object-level, emotional stimuli benefit from a stimulus-specific boost in
      visual attention at the relative expense of competing stimuli. At the visual
      feature-level, recent findings indicate that emotion may inhibit the processing
      of small visual details and facilitate the processing of coarse visual features.
      In the present study, we investigated whether emotion can boost the activation
      and inhibition of automatic motor responses that are generated prior to overt
      perception. To investigate this, we tested whether an emotional cue affects
      covert motor responses in a masked priming task. We used a masked priming
      paradigm in which participants responded to target arrows that were preceded by
      invisible congruent or incongruent prime arrows. In the standard paradigm,
      participants react faster, and commit fewer errors responding to the
      directionality of target arrows, when they are preceded by congruent vs.
      incongruent masked prime arrows (positive congruency effect, PCE). However, as
      prime-target SOAs increase, this effect reverses (negative congruency effect,
      NCE). These findings have been explained as evidence for an initial activation
      and a subsequent inhibition of a partial response elicited by the masked prime
      arrow. Our results show that the presentation of fearful face cues, compared to
      neutral face cues, increased the size of both the PCE and NCE, despite the fact
      that the primes were invisible. This is the first demonstration that emotion
      prepares an individual's visuomotor system for automatic activation and
      inhibition of motor responses in the absence of visual awareness.

PMID- 23162443
TI  - The detrimental effects of emotional process dysregulation on decision-making in
      substance dependence.
AB  - Substance dependence is complex and multifactorial, with many distinct pathways
      involved in both the development and subsequent maintenance of addictive
      behaviors. Various cognitive mechanisms have been implicated, including
      impulsivity, compulsivity, and impaired decision-making. These mechanisms are
      modulated by emotional processes, resulting in increased likelihood of initial
      drug use, sustained substance dependence, and increased relapse during periods of
      abstinence. Emotional traits, such as sensation-seeking, are risk factors for
      substance use, and chronic drug use can result in further emotional dysregulation
      via effects on reward, motivation, and stress systems. We will explore theories
      of hyper and hypo sensitivity of the brain reward systems that may underpin
      motivational abnormalities and anhedonia. Disturbances in these systems
      contribute to the biasing of emotional processing toward cues related to drug use
      at the expense of natural rewards, which serves to maintain addictive behavior,
      via enhanced drug craving. We will additionally focus on the sensitization of the
      brain stress systems that result in negative affect states that continue into
      protracted abstinence that is may lead to compulsive drug-taking. We will explore
      how these emotional dysregulations impact upon decision-making controlled by goal
      directed and habitual action selections systems, and, in combination with a
      failure of prefrontal inhibitory control, mediate maladaptive decision-making
      observed in substance dependent individuals such that they continue drug use in
      spite of negative consequences. An understanding of the emotional impacts on
      cognition in substance dependent individuals may guide the development of more
      effective therapeutic interventions.

PMID- 23162448
TI  - Orexin/hypocretin (Orx/Hcrt) transmission and drug-seeking behavior: is the
      paraventricular nucleus of the thalamus (PVT) part of the drug seeking circuitry?
AB  - The orexin/hypocretin (Orx/Hcrt) system has long been considered to regulate a
      wide range of physiological processes, including feeding, energy metabolism, and
      arousal. More recently, concordant observations have demonstrated an important
      role for these peptides in the reinforcing properties of most drugs of abuse.
      Orx/Hcrt neurons arise in the lateral hypothalamus (LH) and project to all brain
      structures implicated in the regulation of arousal, stress, and reward. Although
      Orx/Hcrt neurons have been shown to massively project to the paraventricular
      nucleus of the thalamus (PVT), only recent evidence suggested that the PVT may be
      a key relay of Orx/Hcrt-coded reward-related communication between the LH and
      both the ventral and dorsal striatum. While this thalamic region was not thought
      to be part of the "drug addiction circuitry," an increasing amount of evidence
      demonstrated that the PVT-particularly PVT Orx/Hcrt transmission-was implicated
      in the modulation of reward function in general and several aspects of drug
      directed behaviors in particular. The present review discusses recent findings
      that suggest that maladaptive recruitment of PVT Orx/Hcrt signaling by drugs of
      abuse may promote persistent compulsive drug-seeking behavior following a period
      of protracted abstinence and as such may represent a relevant target for
      understanding the long-term vulnerability to drug relapse after withdrawal.

PMID- 23162449
TI  - Enhanced conditioned eyeblink response acquisition and proactive interference in
      anxiety vulnerable individuals.
AB  - In classical conditioning, proactive interference may arise from experience with
      the conditioned stimulus (CS), the unconditional stimulus (US), or both, prior to
      their paired presentations. Interest in the application of proactive interference
      has extended to clinical populations as either a risk factor for disorders or as
      a secondary sign. Although the current literature is dense with comparisons of
      stimulus pre-exposure effects in animals, such comparisons are lacking in human
      subjects. As such, interpretation of proactive interference over studies as well
      as its generalization and utility in clinical research is limited. The present
      study was designed to assess eyeblink response acquisition after equal numbers of
      CS, US, and explicitly unpaired CS and US pre-exposures, as well as to evaluate
      how anxiety vulnerability might modulate proactive interference. In the current
      study, anxiety vulnerability was assessed using the State/Trait Anxiety
      Inventories as well as the adult and retrospective measures of behavioral
      inhibition (AMBI and RMBI, respectively). Participants were exposed to 1 of 4
      possible pre-exposure contingencies: 30 CS, 30 US, 30 CS, and 30 US explicitly
      unpaired pre-exposures, or Context pre-exposure, immediately prior to standard
      delay training. Robust proactive interference was evident in all pre-exposure
      groups relative to Context pre-exposure, independent of anxiety classification,
      with CR acquisition attenuated at similar rates. In addition, trait anxious
      individuals were found to have enhanced overall acquisition as well as greater
      proactive interference relative to non-vulnerable individuals. The findings
      suggest that anxiety vulnerable individuals learn implicit associations faster,
      an effect which persists after the introduction of new stimulus contingencies.
      This effect is not due to enhanced sensitivity to the US. Such differences would
      have implications for the development of anxiety psychopathology within a
      learning framework.

PMID- 23162450
TI  - Integrating intention and context: assessing social cognition in adults with
      Asperger syndrome.
AB  - Deficits in social cognition are an evident clinical feature of the Asperger
      syndrome (AS). Although many daily life problems of adults with AS are related to
      social cognition impairments, few studies have conducted comprehensive research
      in this area. The current study examined multiple domains of social cognition in
      adults with AS assessing the executive functions (EF) and exploring the intra and
      inter-individual variability. Fifteen adult's diagnosed with AS and 15 matched
      healthy controls completed a battery of social cognition tasks. This battery
      included measures of emotion recognition, theory of mind (ToM), empathy, moral
      judgment, social norms knowledge, and self-monitoring behavior in social
      settings. We controlled for the effect of EF and explored the individual
      variability. The results indicated that adults with AS had a fundamental deficit
      in several domains of social cognition. We also found high variability in the
      social cognition tasks. In these tasks, AS participants obtained mostly subnormal
      performance. EF did not seem to play a major role in the social cognition
      impairments. Our results suggest that adults with AS present a pattern of social
      cognition deficits characterized by the decreased ability to implicitly encode
      and integrate contextual information in order to access to the social meaning.
      Nevertheless, when social information is explicitly presented or the situation
      can be navigated with abstract rules, performance is improved. Our findings have
      implications for the diagnosis and treatment of individuals with AS as well as
      for the neurocognitive models of this syndrome.

PMID- 23162452
TI  - The effects of visual imagery on face identification: an ERP study.
AB  - The present study tested the hypothesis that the effects of mental imagery on
      subsequent perception occur at a later matching stage in perceptual
      identification, but not in the early perceptual stage as in perceptual detection.
      The behavioral results suggested that the effect of visual imagery on visual
      identification is content-specific, i.e., imagining a congruent face facilitates
      face identification, whereas a mismatch between imagery and perception leads to
      an interference effect. More importantly, the ERP results revealed that a more
      negative N2 response to the subsequent visual face stimuli was elicited over
      fronto-central sites in the mismatch and no-imagery conditions as compared to
      that in the match condition, with the early P1 and N170 components independent of
      manipulations. The latency and distribution of the neural effects demonstrate
      that the matching step, but not the earlier perceptual process, is affected by
      the preceding visual imagery in the context of face identification. We discuss
      these results in a broader context that the imagery-perception interaction may
      depend on task demand.

PMID- 23162451
TI  - Event-related potential studies of outcome processing and feedback-guided
      learning.
AB  - In order to control behavior in an adaptive manner the brain has to learn how
      some situations and actions predict positive or negative outcomes. During the
      last decade cognitive neuroscientists have shown that the brain is able to
      evaluate and learn from outcomes within a few hundred milliseconds of their
      occurrence. This research has been primarily focused on the feedback-related
      negativity (FRN) and the P3, two event-related potential (ERP) components that
      are elicited by outcomes. The FRN is a frontally distributed negative-polarity
      ERP component that typically reaches its maximal amplitude 250 ms after outcome
      presentation and tends to be larger for negative than for positive outcomes. The
      FRN has been associated with activity in the anterior cingulate cortex (ACC). The
      P3 (~300-600 ms) is a parietally distributed positive-polarity ERP component that
      tends to be larger for large magnitude than for small magnitude outcomes. The
      neural sources of the P3 are probably distributed over different regions of the
      cortex. This paper examines the theories that have been proposed to explain the
      functional role of these two ERP components during outcome processing. Special
      attention is paid to extant literature addressing how these ERP components are
      modulated by outcome valence (negative vs. positive), outcome magnitude (large
      vs. small), outcome probability (unlikely vs. likely), and behavioral adjustment.
      The literature offers few generalizable conclusions, but is beset with a number
      of inconsistencies across studies. This paper discusses the potential reasons for
      these inconsistencies and points out some challenges that probably will shape the
      field over the next decade.

PMID- 23162453
TI  - Hippocampal volume varies with educational attainment across the life-span.
AB  - Socioeconomic disparities-and particularly differences in educational attainment
      are associated with remarkable differences in cognition and behavior across the
      life-span. Decreased educational attainment has been linked to increased exposure
      to life stressors, which in turn have been associated with structural differences
      in the hippocampus and the amygdala. However, the degree to which educational
      attainment is directly associated with anatomical differences in these structures
      remains unclear. Recent studies in children have found socioeconomic differences
      in regional brain volume in the hippocampus and amygdala across childhood and
      adolescence. Here we expand on this work, by investigating whether disparities in
      hippocampal and amygdala volume persist across the life-span. In a sample of 275
      individuals from the BRAINnet Foundation database ranging in age from 17 to 87,
      we found that socioeconomic status (SES), as operationalized by years of
      educational attainment, moderates the effect of age on hippocampal volume.
      Specifically, hippocampal volume tended to markedly decrease with age among less
      educated individuals, whereas age-related reductions in hippocampal volume were
      less pronounced among more highly educated individuals. No such effects were
      found for amygdala volume. Possible mechanisms by which education may buffer age
      related effects on hippocampal volume are discussed.

PMID- 23162454
TI  - P300 amplitudes in the concealed information test are less affected by depth of
      processing than electrodermal responses.
AB  - The Concealed Information Test (CIT) has been used in the laboratory as well as
      in field applications to detect concealed crime related memories. The
      presentation of crime relevant details to guilty suspects has been shown to
      elicit enhanced N200 and P300 amplitudes of the event-related brain potentials
      (ERPs) as well as greater skin conductance responses (SCRs) as compared to
      neutral test items. These electrophysiological and electrodermal responses were
      found to incrementally contribute to the validity of the test, thereby suggesting
      that these response systems are sensitive to different psychological processes.
      In the current study, we tested whether depth of processing differentially
      affects N200, P300, and SCR amplitudes in the CIT. Twenty participants carried
      out a mock crime and became familiar with central and peripheral crime details. A
      CIT that was conducted 1 week later revealed that SCR amplitudes were larger for
      central details although central and peripheral items were remembered equally
      well in a subsequent explicit memory test. By contrast, P300 amplitudes elicited
      by crime related details were larger but did not differ significantly between
      question types. N200 amplitudes did not allow for detecting concealed knowledge
      in this study. These results indicate that depth of processing might be one
      factor that differentially affects central and autonomic nervous system responses
      to concealed information. Such differentiation might be highly relevant for field
      applications of the CIT.

PMID- 23162455
TI  - The hemispheric lateralization of speech processing depends on what "speech" is:
      a hierarchical perspective.

PMID- 23162456
TI  - Abstract art and cortical motor activation: an EEG study.
AB  - The role of the motor system in the perception of visual art remains to be better
      understood. Earlier studies on the visual perception of abstract art (from
      Gestalt theory, as in Arnheim, 1954 and 1988, to balance preference studies as in
      Locher and Stappers, 2002, and more recent work by Locher et al., 2007; Redies,
      2007, and Taylor et al., 2011), neglected the question, while the field of
      neuroesthetics (Ramachandran and Hirstein, 1999; Zeki, 1999) mostly concentrated
      on figurative works. Much recent work has demonstrated the multimodality of
      vision, encompassing the activation of motor, somatosensory, and viscero-motor
      brain regions. The present study investigated whether the observation of high
      resolution digitized static images of abstract paintings by Lucio Fontana is
      associated with specific cortical motor activation in the beholder's brain. Mu
      rhythm suppression was evoked by the observation of original art works but not by
      control stimuli (as in the case of graphically modified versions of these works).
      Most interestingly, previous visual exposure to the stimuli did not affect the mu
      rhythm suppression induced by their observation. The present results clearly show
      the involvement of the cortical motor system in the viewing of static abstract
      art works.

PMID- 23162457
TI  - Triphasic spike-timing-dependent plasticity organizes networks to produce robust
      sequences of neural activity.
AB  - Synfire chains have long been proposed to generate precisely timed sequences of
      neural activity. Such activity has been linked to numerous neural functions
      including sensory encoding, cognitive and motor responses. In particular, it has
      been argued that synfire chains underlie the precise spatiotemporal firing
      patterns that control song production in a variety of songbirds. Previous studies
      have suggested that the development of synfire chains requires either initial
      sparse connectivity or strong topological constraints, in addition to any
      synaptic learning rules. Here, we show that this necessity can be removed by
      using a previously reported but hitherto unconsidered spike-timing-dependent
      plasticity (STDP) rule and activity-dependent excitability. Under this rule the
      network develops stable synfire chains that possess a non-trivial, scalable multi
      layer structure, in which relative layer sizes appear to follow a universal
      function. Using computational modeling and a coarse grained random walk model, we
      demonstrate the role of the STDP rule in growing, molding and stabilizing the
      chain, and link model parameters to the resulting structure.

PMID- 23162459
TI  - Order Patterns Networks (ORPAN)-a method to estimate time-evolving functional
      connectivity from multivariate time series.
AB  - Complex networks provide an excellent framework for studying the function of the
      human brain activity. Yet estimating functional networks from measured signals is
      not trivial, especially if the data is non-stationary and noisy as it is often
      the case with physiological recordings. In this article we propose a method that
      uses the local rank structure of the data to define functional links in terms of
      identical rank structures. The method yields temporal sequences of networks which
      permits to trace the evolution of the functional connectivity during the time
      course of the observation. We demonstrate the potentials of this approach with
      model data as well as with experimental data from an electrophysiological study
      on language processing.

PMID- 23162460
TI  - An emerging consensus for open evaluation: 18 visions for the future of
      scientific publishing.

PMID- 23162458
TI  - Seeing via Miniature Eye Movements: A Dynamic Hypothesis for Vision.
AB  - During natural viewing, the eyes are never still. Even during fixation, miniature
      movements of the eyes move the retinal image across tens of foveal
      photoreceptors. Most theories of vision implicitly assume that the visual system
      ignores these movements and somehow overcomes the resulting smearing. However,
      evidence has accumulated to indicate that fixational eye movements cannot be
      ignored by the visual system if fine spatial details are to be resolved. We argue
      that the only way the visual system can achieve its high resolution given its
      fixational movements is by seeing via these movements. Seeing via eye movements
      also eliminates the instability of the image, which would be induced by them
      otherwise. Here we present a hypothesis for vision, in which coarse details are
      spatially encoded in gaze-related coordinates, and fine spatial details are
      temporally encoded in relative retinal coordinates. The temporal encoding
      presented here achieves its highest resolution by encoding along the elongated
      axes of simple-cell receptive fields and not across these axes as suggested by
      spatial models of vision. According to our hypothesis, fine details of shape are
      encoded by inter-receptor temporal phases, texture by instantaneous intra-burst
      rates of individual receptors, and motion by inter-burst temporal frequencies. We
      further describe the ability of the visual system to readout the encoded
      information and recode it internally. We show how reading out of retinal signals
      can be facilitated by neuronal phase-locked loops (NPLLs), which lock to the
      retinal jitter; this locking enables recoding of motion information and temporal
      framing of shape and texture processing. A possible implementation of this
      locking-and-recoding process by specific thalamocortical loops is suggested.
      Overall it is suggested that high-acuity vision is based primarily on temporal
      mechanisms of the sort presented here and low-acuity vision is based primarily on
      spatial mechanisms.

PMID- 23162461
TI  - Metabolic efficiency with fast spiking in the squid axon.
AB  - Fundamentally, action potentials in the squid axon are consequence of the
      entrance of sodium ions during the depolarization of the rising phase of the
      spike mediated by the outflow of potassium ions during the hyperpolarization of
      the falling phase. Perfect metabolic efficiency with a minimum charge needed for
      the change in voltage during the action potential would confine sodium entry to
      the rising phase and potassium efflux to the falling phase. However, because
      sodium channels remain open to a significant extent during the falling phase, a
      certain overlap of inward and outward currents is observed. In this work we
      investigate the impact of ion overlap on the number of the adenosine triphosphate
      (ATP) molecules and energy cost required per action potential as a function of
      the temperature in a Hodgkin-Huxley model. Based on a recent approach to
      computing the energy cost of neuronal action potential generation not based on
      ion counting, we show that increased firing frequencies induced by higher
      temperatures imply more efficient use of sodium entry, and then a decrease in the
      metabolic energy cost required to restore the concentration gradients after an
      action potential. Also, we determine values of sodium conductance at which the
      hydrolysis efficiency presents a clear minimum.

PMID- 23162462
TI  - Varicella-zoster virus keratitis with asymptomatic conjunctival viral shedding in
      the contralateral eye.
AB  - PURPOSE: To report a case of varicella-zoster virus (VZV) keratitis with
      detection of VZV DNA in the tear fluid of not only the symptomatic eye but also
      the contralateral asymptomatic eye by polymerase chain reaction (PCR). METHODS:
      This is a case report. A 63-year-old otherwise healthy woman presented with
      circular corneal ulcer and stromal opacity with infiltration accompanied by mild
      conjunctival and ciliary injections in the left eye. Bacterial cultures of the
      corneal scrapings and virus PCR analyses of tear fluid from both eyes were
      performed. RESULTS: No pathogen was found by bacterial cultures. PCR was negative
      for Acanthamoeba, herpes simplex virus and cytomegalovirus, but positive for VZV.
      VZV DNA was also detected in the unaffected eye. Based on the diagnosis of VZV
      keratitis, oral valacyclovir and acyclovir eye ointment were administered to the
      corneal infected eye. The infected eye was healed and VZV DNA turned negative in
      the tear fluid of the treated eye after 6 months of treatment; however, VZV DNA
      was still positive in the tear fluid of the contralateral eye. CONCLUSIONS: To
      our knowledge, this is the first case report of the detection of VZV DNA in the
      tear fluid of both affected and unaffected eyes in a patient with VZV keratitis.
      Asymptomatic conjunctival shedding of VZV may continue in the healthy unaffected
      eye in VZV keratitis patients.

PMID- 23162463
TI  - Virtual navigation strategies from childhood to senescence: evidence for changes
      across the life span.
AB  - This study sought to investigate navigational strategies across the life span, by
      testing 8-years old children to 80-years old healthy older adults on the 4 on 8
      virtual maze (4/8VM). The 4/8VM was previously developed to assess spontaneous
      navigational strategies, i.e., hippocampal-dependent spatial strategies
      (navigation by memorizing relationships between landmarks) versus caudate nucleus
      dependent response strategies (memorizing a series of left and right turns from a
      given starting position). With the 4/8VM, we previously demonstrated greater fMRI
      activity and gray matter in the hippocampus of spatial learners relative to
      response learners. A sample of 599 healthy participants was tested in the current
      study. Results showed that 84.4% of children, 46.3% of young adults, and 39.3% of
      older adults spontaneously used spatial strategies (p < 0.0001). Our results
      suggest that while children predominantly use spatial strategies, the proportion
      of participants using spatial strategies decreases across the life span, in favor
      of response strategies. Factors promoting response strategies include repetition,
      reward and stress. Since response strategies can result from successful
      repetition of a behavioral pattern, we propose that the increase in response
      strategies is a biological adaptive mechanism that allows for the automatization
      of behavior such as walking in order to free up hippocampal-dependent resources.
      However, the down-side of this shift from spatial to response strategies occurs
      if people stop building novel relationships, which occurs with repetition and
      routine, and thereby stop stimulating their hippocampus. Reduced fMRI activity
      and gray matter in the hippocampus were shown to correlate with cognitive
      deficits in normal aging. Therefore, these results have important implications
      regarding factors involved in healthy and successful aging.

PMID- 23162464
TI  - Brain volumetric and microstructural correlates of executive and motor
      performance in aged rhesus monkeys.
AB  - The aged rhesus macaque exhibits brain atrophy and behavioral deficits similar to
      normal aging in humans. Here we studied the association between cognitive and
      motor performance and anatomic and microstructural brain integrity measured with
      3T magnetic resonance imaging in aged monkeys. About half of these animals were
      maintained on moderate calorie restriction (CR), the only intervention shown to
      delay the aging process in lower animals. T1-weighted anatomic and diffusion
      tensor images were used to obtain gray matter (GM) volume and fractional
      anisotropy (FA) and mean diffusivity (MD), respectively. We tested the extent to
      which brain health indexed by GM volume, FA, and MD were related to executive and
      motor function, and determined the effect of the dietary intervention on this
      relationship. We hypothesized that fewer errors on the executive function test
      and faster motor response times would be correlated with higher volume, higher
      FA, and lower MD in frontal areas that mediate executive function, and in motor,
      premotor, subcortical, and cerebellar areas underlying goal-directed motor
      behaviors. Higher error percentage on a cognitive conceptual shift task was
      significantly associated with lower GM volume in frontal and parietal cortices,
      and lower FA in major association fiber bundles. Similarly, slower performance
      time on the motor task was significantly correlated with lower volumetric
      measures in cortical, subcortical, and cerebellar areas and decreased FA in
      several major association fiber bundles. Notably, performance during the
      acquisition phase of the hardest level of the motor task was significantly
      associated with anterior mesial temporal lobe volume. Finally, these brain
      behavior correlations for the motor task were attenuated in CR animals compared
      to controls, indicating a potential protective effect of the dietary
      intervention.

PMID- 23162465
TI  - Interleukin-6 modulates colonic transepithelial ion transport in the stress
      sensitive wistar kyoto rat.
AB  - Immunological challenge stimulates secretion of the pro-inflammatory cytokine
      interleukin (IL)-6, resulting in variety of biological responses. In the
      gastrointestinal tract, IL-6 modulates the excitability of submucosal neurons and
      stimulates secretion into the colonic lumen. When considered in the context of
      the functional bowel disorder, irritable bowel syndrome (IBS), where plasma
      levels of IL-6 are elevated, this may reflect an important molecular mechanism
      contributing to symptom flares, particularly in the diarrhea-predominant
      phenotype. In these studies, colonic ion transport, an indicator of absorption
      and secretion, was assessed in the stress-sensitive Wistar Kyoto (WKY) rat model
      of IBS. Mucosa-submucosal colonic preparations from WKY and control Sprague
      Dawley (SD) rats were mounted in Ussing chambers and the basal short circuit
      current (I(SC)) was electrophysiologically recorded and compared between the
      strains. Exposure to IL-6 (1 nM) stimulated a secretory current of greater
      amplitude in WKY as compared to SD samples. Furthermore, the observed IL-6
      mediated potentiation of secretory currents evoked by veratridine and capsaicin
      in SD rats was blunted in WKY rats. Exposure to IL-6 also stimulated an increase
      in transepithelial resistance in both SD and WKY colonic tissue. These studies
      demonstrate that the neuroexcitatory effects of IL-6 on submucosal plexi have
      functional consequences with alterations in both colonic secretory activity and
      permeability. The IL-6-induced increase in colonic secretory activity appears to
      neurally mediated. Thus, local increases in IL-6 levels and subsequent activation
      of enteric neurons may underlie alterations in absorpto-secretory function in the
      WKY model of IBS.

PMID- 23162466
TI  - Metastasis-associated cell surface oncoproteomics.
AB  - Oncoproteomics aims to the discovery of molecular markers, drug targets, and
      pathways by studying cancer specific protein expression, localization,
      modification, and interaction. Cell surface proteins play a central role in
      several pathological conditions, including cancer and its metastatic spread.
      However, cell surface proteins are underrepresented in proteomics analyses
      performed from the whole cell extracts due to their hydrophobicity and low
      abundance. Different methods have been developed to enrich and isolate the cell
      surface proteins to reduce sample complexity. Despite the method selected, the
      primary difficulty encountered is the solubilization of the hydrophobic
      transmembrane proteins from the lipid bilayer. This review focuses on proteomic
      analyses of metastasis-associated proteins identified using the cell surface
      biotinylation method. Interestingly, also certain intracellular proteins were
      identified from the cell surface samples. The function of these proteins at the
      cell surface might well differ from their function inside the cell.

PMID- 23162467
TI  - The Role of Human Aldo-Keto Reductases in the Metabolic Activation and
      Detoxication of Polycyclic Aromatic Hydrocarbons: Interconversion of PAH
      Catechols and PAH o-Quinones.
AB  - Polycyclic aromatic hydrocarbons (PAH) are ubiquitous environmental pollutants.
      They are procarcinogens requiring metabolic activation to elicit their
      deleterious effects. Aldo-keto reductases (AKR) catalyze the oxidation of
      proximate carcinogenic PAH trans-dihydrodiols to yield electrophilic and redox
      active PAH o-quinones. AKRs are also found to be capable of reducing PAH o
      quinones to form PAH catechols. The interconversion of o-quinones and catechols
      results in the redox-cycling of PAH o-quinones to give rise to the generation of
      reactive oxygen species and subsequent oxidative DNA damage. On the other hand,
      PAH catechols can be intercepted through phase II metabolism by which PAH o
      quinones could be detoxified and eliminated. The aim of the present review is to
      summarize the role of human AKRs in the metabolic activation/detoxication of PAH
      and the relevance of phase II conjugation reactions to human lung carcinogenesis.

PMID- 23162468
TI  - Differential progressive remodeling of coronary and cerebral arteries and
      arterioles in an aortic coarctation model of hypertension.
AB  - OBJECTIVES: Effects of hypertension on arteries and arterioles often manifest
      first as a thickened wall, with associated changes in passive material properties
      (e.g., stiffness) or function (e.g., cellular phenotype, synthesis and removal
      rates, and vasomotor responsiveness). Less is known, however, regarding the
      relative evolution of such changes in vessels from different vascular beds.
      METHODS: We used an aortic coarctation model of hypertension in the mini-pig to
      elucidate spatiotemporal changes in geometry and wall composition (including
      layer-specific thicknesses as well as presence of collagen, elastin, smooth
      muscle, endothelial, macrophage, and hematopoietic cells) in three different
      arterial beds, specifically aortic, cerebral, and coronary, and vasodilator
      function in two different arteriolar beds, the cerebral and coronary. RESULTS:
      Marked geometric and structural changes occurred in the thoracic aorta and left
      anterior descending coronary artery within 2 weeks of the establishment of
      hypertension and continued to increase over the 8-week study period. In contrast,
      no significant changes were observed in the middle cerebral arteries from the
      same animals. Consistent with these differential findings at the arterial level,
      we also found a diminished nitric oxide-mediated dilation to adenosine at 8 weeks
      of hypertension in coronary arterioles, but not cerebral arterioles. CONCLUSION:
      These findings, coupled with the observation that temporal changes in wall
      constituents and the presence of macrophages differed significantly between the
      thoracic aorta and coronary arteries, confirm a strong differential progressive
      remodeling within different vascular beds. Taken together, these results suggest
      a spatiotemporal progression of vascular remodeling, beginning first in large
      elastic arteries and delayed in distal vessels.

PMID- 23162469
TI  - The force-temperature relationship in healthy and dystrophic mouse diaphragm;
      implications for translational study design.
AB  - In the field of muscular dystrophy, striated muscle function is often assessed in
      vitro in dystrophin-deficient mdx mice in order to test the impact of a potential
      treatment strategy. Although many past studies have assessed diaphragm
      contractile function at or near room temperature, the diaphragm performs in vivo
      at 37 degrees C. To improve translation of bench-top results to possible clinical
      application, we studied temperature-dependence of contractile performance in wild
      type (C57BL/10) and mdx muscle strips at temperatures from 25 degrees C to 37
      degrees C. Maximal tetanic force in wild-type muscles was higher at 37 degrees C
      (198 +/- 11 vs. 155 +/- 9 mN/mm(2) at 25 degrees C), while the difference between
      wild-type and mdx was extremely similar: wild-type muscles produced 45.9% and
      45.1% more force at 25 degrees C and 37 degrees C respectively. At 37 degrees C
      twitch contraction kinetics and 50% rise time to tetanic plateau were slower in
      mdx diaphragm. A fatigue/injury protocol indicated 2-fold fatigue/contraction
      induced force deficit in mdx muscles. We conclude that assessment of diaphragm
      muscle strips can be reliably and reproducibly performed at 37 degrees C.

PMID- 23162471
TI  - How cholesterol regulates endothelial biomechanics.
AB  - As endothelial cells form the barrier between blood flow and surrounding tissue,
      many of their functions depend on mechanical integrity, in particular those of
      the plasma membrane. As component and organizer of the plasma membrane,
      cholesterol is a regulator of cellular mechanical properties. Disruption of
      cholesterol balance leads to impairment of endothelial functions and eventually
      to disease. The mechanical properties of the membrane are strongly affected by
      the cytoskeleton. As Phosphatidylinositol-4,5-bisphosphate (PIP2) is a key
      mediator between the membrane and cytoskeleton, it also affects cellular
      biomechanical properties. Typically, PIP2 is concentrated in cholesterol-rich
      microdomains, such as caveolae and lipid rafts, which are particularly abundant
      in the endothelial plasma membrane. We investigated the connection between
      cholesterol and PIP2 by extracting membrane tethers from bovine aortic
      endothelial cells (BAEC) at different cholesterol levels and PIP2 conditions. Our
      results suggest that in BAEC the role of PIP2, as a mediator of membrane
      cytoskeleton adhesion, is regulated by cholesterol. Our findings confirm the
      specific role of cholesterol in endothelial cells and may have implications for
      cholesterol-dependent vascular pathologies.

PMID- 23162472
TI  - Developing organized level of biomedical evidence: evidence-based biomedicine.

PMID- 23162473
TI  - MSX2 in pancreatic tumor development and its clinical application for the
      diagnosis of pancreatic ductal adenocarcinoma.
AB  - MSX2, a member of the homeobox genes family, is demonstrated to be the downstream
      target for ras signaling pathway and is expressed in a variety of carcinoma
      cells, suggesting its relevance to the development of ductal pancreatic tumors
      since pancreatic ductal adenocarcinoma (PDAC) and intraductal papillary-mucinous
      neoplasia (IPMN) harbor frequent K-ras gene mutations. Recent studies revealed
      the roles of MSX2 in the development of carcinoma of various origins including
      pancreas. Among gastrointestinal tumors, PDAC is one of the most malignant. PDAC
      progresses rapidly to develop metastatic lesions, frequently by the time of
      diagnosis, and these tumors are usually resistant to conventional chemotherapy
      and radiation therapy. The molecular mechanisms regulating the aggressive
      behavior of PDAC still remain to be clarified. On the other hand, IPMN of the
      pancreas is distinct from PDAC because of its intraductal growth in the main
      pancreatic duct or secondary branches with rare invasion and metastasis to
      distant organs. However, recent evidence indicated that once IPMN showed stromal
      invasion, it progresses like PDAC. Therefore, it is important to determin how
      IPMN progresses to malignant phenotype. In this review, we focus on the
      involvement of MSX2 in the enhancement of malignant behavior in PDAC and IPMN,
      and further highlight the clinical approach to differentiate PDAC from chronic
      pancreatitis by evaluating MSX2 expression level.

PMID- 23162470
TI  - Vulnerability of the developing brain to hypoxic-ischemic damage: contribution of
      the cerebral vasculature to injury and repair?
AB  - As clinicians attempt to understand the underlying reasons for the vulnerability
      of different regions of the developing brain to injury, it is apparent that
      little is known as to how hypoxia-ischemia may affect the cerebrovasculature in
      the developing infant. Most of the research investigating the pathogenesis of
      perinatal brain injury following hypoxia-ischemia has focused on excitotoxicity,
      oxidative stress and an inflammatory response, with the response of the
      developing cerebrovasculature receiving less attention. This is surprising as the
      presentation of devastating and permanent injury such as germinal matrix
      intraventricular haemorrhage (GM-IVH) and perinatal stroke are of vascular
      origin, and the origin of periventricular leukomalacia (PVL) may also arise from
      poor perfusion of the white matter. This highlights that cerebrovasculature
      injury following hypoxia could primarily be responsible for the injury seen in
      the brain of many infants diagnosed with hypoxic-ischemic encephalopathy (HIE).
      Interestingly the highly dynamic nature of the cerebral blood vessels in the
      fetus, and the fluctuations of cerebral blood flow and metabolic demand that
      occur following hypoxia suggest that the response of blood vessels could explain
      both regional protection and vulnerability in the developing brain. However,
      research into how blood vessels respond following hypoxia-ischemia have mostly
      been conducted in adult models of ischemia or stroke, further highlighting the
      need to investigate how the developing cerebrovasculature responds and the
      possible contribution to perinatal brain injury following hypoxia. This review
      discusses the current concepts on the pathogenesis of perinatal brain injury, the
      development of the fetal cerebrovasculature and the blood brain barrier (BBB),
      and key mediators involved with the response of cerebral blood vessels to
      hypoxia.

PMID- 23162475
TI  - Does C-reactive protein contribute to atherothrombosis via oxidant-mediated
      release of pro-thrombotic factors and activation of platelets?
AB  - Inflammation and the generation of reactive oxygen species (ROS) have been
      implicated in the initiation and progression of atherosclerosis. Although C
      reactive protein (CRP) has traditionally been considered to be a biomarker of
      inflammation, recent in vitro and in vivo studies have provided evidence that
      CRP, itself, exerts pro-thrombotic effects on vascular cells and may thus play a
      critical role in the development of atherothrombosis. Of particular importance is
      that CRP interacts with Fcgamma receptors on cells of the vascular wall giving
      rise to the release of pro-thrombotic factors. The present review focuses on
      distinct sources of CRP-mediated ROS generation as well as the pivotal role of
      ROS in CRP-induced tissue factor expression. These studies provide considerable
      insight into the role of the oxidative mechanisms in CRP-mediated stimulation of
      pro-thrombotic factors and activation of platelets. Collectively, the available
      data provide strong support for ROS playing an important intermediary role in the
      relationship between CRP and atherothrombosis.

PMID- 23162476
TI  - Aquaporins in fishes-expression, localization, and functional dynamics.

PMID- 23162474
TI  - Multiple functions of the crustacean gill: osmotic/ionic regulation, acid-base
      balance, ammonia excretion, and bioaccumulation of toxic metals.
AB  - The crustacean gill is a multi-functional organ, and it is the site of a number
      of physiological processes, including ion transport, which is the basis for
      hemolymph osmoregulation; acid-base balance; and ammonia excretion. The gill is
      also the site by which many toxic metals are taken up by aquatic crustaceans, and
      thus it plays an important role in the toxicology of these species. This review
      provides a comprehensive overview of the ecology, physiology, biochemistry, and
      molecular biology of the mechanisms of osmotic and ionic regulation performed by
      the gill. The current concepts of the mechanisms of ion transport, the
      structural, biochemical, and molecular bases of systemic physiology, and the
      history of their development are discussed. The relationship between branchial
      ion transport and hemolymph acid-base regulation is also treated. In addition,
      the mechanisms of ammonia transport and excretion across the gill are discussed.
      And finally, the toxicology of heavy metal accumulation via the gill is reviewed
      in detail.

PMID- 23162478
TI  - Collaboration: The Paradigm of Practice Approach between the Forensic
      Psychiatrist and the Forensic Psychologist.
AB  - The importance and relevance of forensic practice to societal evolution has
      increased exponentially in recent years. As society evolves in its understanding
      of the complex relationships between mankind and society, we rely more and more
      on the services of forensic experts. This article elucidates the professions of
      forensic psychiatry and forensic psychology. We examine the two distinct
      professions from the spectrum of collaboration, integration of services,
      differences, and similarities. We also compare and contrast the educational
      background and training requirements for these two professions; and present
      illustrative scenarios and real life examples of the daily functions of both
      professionals. Lastly, we present demographic data for the areas of employment,
      numbers, and geographic distribution of the two professions. Forensic psychiatry
      is the interface between medicine and law, while forensic psychology is the
      interface between psychology and law. As such, these professions are mired with
      complexities and challenged by vulnerabilities. Professionals from both fields
      can serve as expert witnesses in court and therefore face similar challenges in
      their course of professional practice. Collaboration between these two
      professions has the potential to increase both the credibility and utility of
      forensic services to the courts, the individuals served, and the general public.

PMID- 23162477
TI  - Systematic review of parameters of stimulation, clinical trial design
      characteristics, and motor outcomes in non-invasive brain stimulation in stroke.
AB  - INTRODUCTION/OBJECTIVES: Repetitive transcranial magnetic stimulation (rTMS) and
      transcranial direct current stimulation are two powerful non-invasive
      neuromodulatory therapies that have the potential to alter and evaluate the
      integrity of the corticospinal tract. Moreover, recent evidence has shown that
      brain stimulation might be beneficial in stroke recovery. Therefore,
      investigating and investing in innovative therapies that may improve
      neurorehabilitative stroke recovery are next steps in research and development.
      Participants/Materials and Methods: This article presents an up-to-date
      systematic review of the treatment effects of rTMS and tDCS on motor function. A
      literary search was conducted, utilizing search terms "stroke" and "transcranial
      stimulation." Items were excluded if they failed to: (1) include stroke patients,
      (2) study motor outcomes, or (3) include rTMS/tDCS as treatments. Other
      exclusions included: (1) reviews, editorials, and letters, (2) animal or
      pediatric populations, (3) case reports or sample sizes <=2 patients, and (4)
      primary outcomes of dysphagia, dysarthria, neglect, or swallowing. RESULTS:
      Investigation of PubMed English Database prior to 01/01/2012 produced 695
      applicable results. Studies were excluded based on the aforementioned criteria,
      resulting in 50 remaining studies. They included 1314 participants (1282 stroke
      patients and 32 healthy subjects) evaluated by motor function pre- and post-tDCS
      or rTMS. Heterogeneity among studies' motor assessments was high and could not be
      accounted for by individual comparison. Pooled effect sizes for the impact of
      post-treatment improvement revealed consistently demonstrable improvements after
      tDCS and rTMS therapeutic stimulation. Most studies provided limited follow-up
      for long-term effects. CONCLUSION: It is apparent from the available studies that
      non-invasive stimulation may enhance motor recovery and may lead to clinically
      meaningful functional improvements in the stroke population. Only mild to no
      adverse events have been reported. Though results have been positive results, the
      large heterogeneity across articles precludes firm conclusions.

PMID- 23162479
TI  - Hippocampal shape and volume changes with antipsychotics in early stage psychotic
      illness.
AB  - Progression of hippocampal shape and volume abnormalities has been described in
      psychotic disorders such as schizophrenia. However it is unclear how specific
      antipsychotic medications influence the development of hippocampal structure. We
      conducted a longitudinal, randomized, controlled, multisite, double-blind study
      involving 14 academic medical centers (United States 11, Canada 1, Netherlands 1,
      and England 1). One hundred thirty-four first-episode psychosis patients
      (receiving either haloperidol [HAL] or olanzapine [OLZ]) and 51 healthy controls
      were followed for up to 104 weeks using magnetic resonance imaging and large
      deformation high-dimensional brain mapping of the hippocampus. Changes in
      hippocampal volume and shape metrics (i.e., percentage of negative surface vertex
      slopes, and surface deformation) were evaluated. Mixed-models analysis did not
      show a significant group-by-time interaction for hippocampal volume. However, the
      cumulative distribution function of hippocampal surface vertex slopes showed a
      notable left shift with HAL treatment compared to OLZ treatment and to controls.
      OLZ treatment was associated with a significantly lower percentage of "large
      magnitude" negative surface vertex slopes compared to HAL treatment (p = 0.004).
      Surface deformation maps however did not localize any hippocampal regions that
      differentially contracted over time with OLZ treatment, after FDR correction.
      These results indicate that surface analysis provides supplementary information
      to volumetry in detecting differential treatment effects of the hippocampus. Our
      results suggest that OLZ is associated with less longitudinal hippocampal surface
      deformation than HAL, however the hippocampal regions affected appear to be
      variable across patients.

PMID- 23162480
TI  - Overview of substance use disorders and incarceration of african american males.
AB  - Incarceration affects the lives of many African American men and often leads to
      poverty, ill health, violence, and a decreased quality of life. There has been an
      unprecedented increase in incarceration among African American males since 1970.
      In 2009, the incarceration rate among black males was 6.7 times that of white
      males and 2.6 times of Hispanic males. Substance abuse in African American males
      leads to higher mortality rates, high rates of alcohol-related problems, more
      likely to be victims of crimes, and HIV/AIDS. African Americans comprised only
      14% of the U.S. population but comprised 38% of the jail population. The cost of
      incarcerating persons involved in substance related crimes has increased
      considerably over the past two decades in the U.S. A reduction in the
      incarceration rate for non-violent offences would save an estimated $17 billion
      per year. Substance use disorder makes the individual more prone to polysubstance
      use and leads to impulse control problems, selling drugs, and other crimes. The
      high rate of incarceration in U.S. may adversely affect health care, the economy
      of the country, and will become a burden on society. Implementation of good
      mental health care, treatment of addiction during and after incarceration will
      help to decrease the chances of reoffending. Therapeutic community programs with
      prison-based and specialized treatment facilities, cognitive behavioral therapy
      treatment for 91-180 days, and 12-step orientation with staff specialized in
      substance abuse can be helpful. It is essential for health care professionals to
      increase public awareness of substance abuse and find ways to decrease the high
      rates of incarceration.

PMID- 23162481
TI  - The dynamics of decision making in risky choice: an eye-tracking analysis.
AB  - In the last years, research on risky choice has moved beyond analyzing choices
      only. Models have been suggested that aim to describe the underlying cognitive
      processes and some studies have tested process predictions of these models.
      Prominent approaches are evidence accumulation models such as decision field
      theory (DFT), simple serial heuristic models such as the adaptive toolbox, and
      connectionist approaches such as the parallel constraint satisfaction (PCS)
      model. In two studies involving measures of attention and pupil dilation, we
      investigate hypotheses derived from these models in choices between two gambles
      with two outcomes each. We show that attention to an outcome of a gamble
      increases with its probability and its value and that attention shifts toward the
      subsequently favored gamble after about two thirds of the decision process,
      indicating a gaze-cascade effect. Information search occurs mostly within
      gambles, and the direction of search does not change over the course of decision
      making. Pupil dilation, which reflects both cognitive effort and arousal,
      increases during the decision process and increases with mean expected value.
      Overall, the results support aspects of automatic integration models for risky
      choice such as DFT and PCS, but in their current specification none of them can
      account for the full pattern of results.

PMID- 23162482
TI  - Effects of social support by a dog on stress modulation in male children with
      insecure attachment.
AB  - Up to 90% of children with special education needs and about 40% of children in
      the general population show insecure or disorganized attachment patterns, which
      are linked to a diminished ability to use social support by others for the
      regulation of stress. The aim of the study was to investigate if children with
      insecure-avoidant/disorganized attachment can profit more from social support by
      a dog compared to a friendly human during a stressful task. We investigated 47
      male children (age 7-11) with insecure-avoidant or disorganized attachment.
      Social stress was elicited via the Trier Social Stress Test for Children (TSST
      C). For one group of children a friendly therapy-dog (n = 24) was present, for
      one control group a friendly human (n = 10) and for the other control group a toy
      dog (n = 13). Stress levels of the children were measured via salivary cortisol
      at five times (t1-t5) before, during, and after the TSST-C and subjective
      reports. The physiological stress response was significantly lower in the dog
      condition in comparison to the two other support conditions at t4, t5 and the
      overall stress reaction from t1 to t5 (Area Under the Curve increase; Kruskal
      Wallis H-Test, pairwise post hoc comparisons via Mann-Whitney U-Tests). Cortisol
      levels correlated negatively (r(s)) with the amount of physical contact between
      the child and dog. We conclude that male children with insecure-avoidant or
      disorganized attachment profit more from the presence of a therapy-dog than of a
      friendly human under social stress. Our findings support the assumption that the
      increasing practice of animal-assisted education is reasonable and that dogs can
      be helpful assistants in education/special education, since stress interferes
      with learning and performance in students.

PMID- 23162483
TI  - Who does well in life? Conscientious adults excel in both objective and
      subjective success.
AB  - This article investigates how personality and cognitive ability relate to
      measures of objective success (income and wealth) and subjective success (life
      satisfaction, positive affect, and lack of negative affect) in a representative
      sample of 9,646 American adults. In cross-sectional analyses controlling for
      demographic covariates, cognitive ability, and other Big Five traits,
      conscientiousness demonstrated beneficial associations of small-to-medium
      magnitude with all success outcomes. In contrast, other traits demonstrated
      stronger, but less consistently beneficial, relations with outcomes in the same
      models. For instance, emotional stability demonstrated medium-to-large
      associations with life satisfaction and affect but a weak association with income
      and no association with wealth. Likewise, extraversion demonstrated medium-to
      large associations with positive affect and life satisfaction but small-to-medium
      associations with wealth and (lack of) negative affect and no association with
      income. Cognitive ability showed small-to-medium associations with income and
      wealth but no association with any aspect of subjective success. More agreeable
      adults were worse off in terms of objective success and life satisfaction,
      demonstrating small-to-medium inverse associations with those outcomes, but they
      did not differ from less agreeable adults in positive or negative affect.
      Likewise, openness to experience demonstrated small-to-medium inverse
      associations with every success outcome except positive affect, in which more
      open adults were slightly higher. Notably, in each of the five models predicting
      objective and subjective success outcomes, individual differences other than
      conscientiousness explained more variance than did conscientiousness. Thus, the
      benefits of conscientiousness may be remarkable more for their ubiquity than for
      their magnitude.

PMID- 23162484
TI  - Context modulates the contribution of time and space in causal inference.
AB  - Humans use kinematic temporal and spatial information from the environment to
      infer the causal dynamics (e.g., force) of an event. We hypothesize that the
      basis for these inferences are malleable and modulated by contextual temporal and
      spatial information. Specifically, the present research investigates whether the
      extent of a person's ongoing experience with direct causal events (e.g.,
      temporally contiguous and spatially continuous) alters their use of time and
      space in judgments of causality. Participants made inferences of causality on
      animated launching events depicting a blue ball colliding with and then
      "launching" a red ball. We parametrically manipulated temporal contiguity and
      spatial continuity by varying the duration of contact between the balls and the
      angle of the second ball's movement. We manipulated participants' level of
      exposure to direct causal events (i.e., events with no delay or angle change)
      between experiments (Experiment 1: 2%, Experiment 2: 25%, Experiment 3: 75%). We
      found that participants adjust the temporal and spatial parameters they use to
      judge causality to accommodate the context in which they apprehended launching
      events. Participants became more conservative in their use of temporal and
      spatial parameters to judge causality as their exposure to direct causal events
      increased. People use time and space flexibly to infer causality based on their
      ongoing experiences. Such flexibility in making causal inferences may have
      adaptive significance.

PMID- 23162485
TI  - Neural correlates of time versus money in product evaluation.
AB  - The common saying "time is money" reflects the widespread belief in many people's
      everyday life that time is valuable like money. Psychologically and
      neurophysiologically, however, these concepts seem to be quite different. This
      research replicates prior behavioral investigations by showing that merely
      mentioning "time" (compared to merely mentioning "money") leads participants to
      evaluate a product more positively. Beyond this finding, the present functional
      magnetic resonance imaging (fMRI) experiment provides novel insight into the
      neurophysiological underpinnings of this behavioral effect by showing that more
      positive product evaluations in the time primes (compared to money primes) are
      preceded by increased activation in the insula. Our data, therefore, support the
      idea of a time mindset that is different from a money mindset. Studies on the
      functional neuroanatomy of the insula have implicated this brain area in distinct
      but related psychological phenomena such as urging, addiction, loss aversion, and
      love. These functions imply greater personal connection between the consumer and
      a target subject or object and, thus, help explain why time-primed consumers rate
      products more positively.

PMID- 23162486
TI  - Enactment of third-party punishment by 4-year-olds.
AB  - When prompted, preschoolers advocate punishment for moral transgressions against
      third parties, but little is known about whether and how they might act out such
      punishment. In this study, adult demonstrators enacted doll stories in which a
      perpetrator child doll made an unprovoked attack on a victim child doll, after
      which an adult doll punished either the perpetrator (consistent punishment) or
      victim (inconsistent punishment). When asked to help retell the story, given free
      choice of their own preferred actions for the adult doll, 4-year-olds (N = 32)
      were influenced by the demonstrated choice of target when selecting a target for
      punishment or admonishment. This influence was weak following inconsistent
      punishment, however, because the participants tended to change the story by
      punishing or admonishing the perpetrator when the demonstrator had punished the
      victim. Four-year-olds' tendency to select a moral rule violator as a target for
      punishment is therefore stronger than their tendency to copy the specific actions
      of adults, which itself is known to be very strong. The evidence suggests that 4
      year-olds' enactment of punishment is at least partially based on a belief that
      antisocial actions deserve to be punished.

PMID- 23162487
TI  - Statistical speech segmentation and word learning in parallel: scaffolding from
      child-directed speech.
AB  - In order to acquire their native languages, children must learn richly structured
      systems with regularities at multiple levels. While structure at different levels
      could be learned serially, e.g., speech segmentation coming before word-object
      mapping, redundancies across levels make parallel learning more efficient. For
      instance, a series of syllables is likely to be a word not only because of high
      transitional probabilities, but also because of a consistently co-occurring
      object. But additional statistics require additional processing, and thus might
      not be useful to cognitively constrained learners. We show that the structure of
      child-directed speech makes simultaneous speech segmentation and word learning
      tractable for human learners. First, a corpus of child-directed speech was
      recorded from parents and children engaged in a naturalistic free-play task.
      Analyses revealed two consistent regularities in the sentence structure of naming
      events. These regularities were subsequently encoded in an artificial language to
      which adult participants were exposed in the context of simultaneous statistical
      speech segmentation and word learning. Either regularity was independently
      sufficient to support successful learning, but no learning occurred in the
      absence of both regularities. Thus, the structure of child-directed speech plays
      an important role in scaffolding speech segmentation and word learning in
      parallel.

PMID- 23162488
TI  - Happily distracted: mood and a benefit of attention dysregulation in older
      adults.
AB  - Positive mood states are believed to broaden the focus of attention in younger
      adults, but it is unclear whether the same is true for older adults. Here we
      examined one consequence of broader attention that has been shown in young
      adults: that memory for distraction is greater for those in a positive mood. In
      the current study, positive and neutral moods were induced in older adults (M =
      67.9) prior to a 1-back task in which participants were instructed to attend to
      relevant pictures and ignore distracting words. Following a 10-min filled
      interval, participants performed a word fragment completion task that tested
      implicit memory for the distracting words from the 1-back task. Older adults in
      the positive mood group showed greater implicit memory for previous distraction
      compared to those in the neutral mood group. These findings suggest that affect
      influences the ability to regulate attention in a similar manner for younger and
      older adults.

PMID- 23162489
TI  - Intentional suppression can lead to a reduction of memory strength: behavioral
      and electrophysiological findings.
AB  - Previous research has shown that the intentional suppression of unwanted memories
      can lead to forgetting in later memory tests. However, the mechanisms underlying
      this effect remain unclear. This study employed recognition memory testing and
      event-related potentials (ERPs) to investigate whether intentional suppression
      leads to the inhibition of memory representations at an item level. In a think/no
      think experiment, participants were cued to either suppress (no-think condition)
      or retrieve (think condition) previously learned words, 18 or 0 times.
      Performance in a final recognition test was significantly reduced for repeatedly
      suppressed no-think items when compared to the baseline, zero-repetition
      condition. ERPs recorded during the suppression of no-think items were
      significantly more negative-going in a time window around 300 ms when compared to
      ERPs in the think condition. This reduction correlated with later recognition
      memory impairment. Furthermore, ERPs to no-think items from 225 to 450 ms were
      more negative-going in later phases of the experiment, suggesting a gradual
      reduction of memory strength with repeated suppression attempts. These effects
      were dissociable from correlates of recollection (500-600 ms) and inhibitory
      control (450-500 ms) that did not vary over the time-course of the experiment and
      appeared to be under strategic control. Our results give strong evidence that the
      no-think manipulation involves inhibition of memory representations at an item
      level.

PMID- 23162491
TI  - When Can Predictive Brains be Truly Bayesian?

PMID- 23162490
TI  - Motivation matters: differing effects of pre-goal and post-goal emotions on
      attention and memory.
AB  - People often show enhanced memory for information that is central to emotional
      events and impaired memory for peripheral details. The intensity of arousal
      elicited by an emotional event is commonly held to be the mechanism underlying
      memory narrowing, with the implication that all sources of emotional arousal
      should have comparable effects. Discrete emotions differ in their effects on
      memory, however, with some emotions broadening rather than narrowing the range of
      information attended to and remembered. Thus, features of emotion other than
      arousal appear to play a critical role in memory narrowing. We review theory and
      research on emotional memory narrowing and argue that motivation matters. Recent
      evidence suggests that emotions experienced prior to goal attainment or loss lead
      to memory narrowing whereas emotions experienced after goal attainment or loss
      broaden the range of information encoded in memory. The motivational component of
      emotion is an important but understudied feature that can help to clarify the
      conditions under which emotions enhance and impair attention and memory.

PMID- 23162492
TI  - A framework for error correction under prediction.

PMID- 23162493
TI  - Predictive memory and the surprising gap.

PMID- 23162494
TI  - Fairness considerations when I know more than you do: developmental comparisons.
AB  - The Ultimatum Game (UG) is a valuable paradigm to study fairness considerations.
      Here, we tested developmental differences between altruistic and strategic
      motivations in fairness considerations using a version of the UG with hidden
      conditions. Participants were proposers and could divide coins between themselves
      and an anonymous other. Hidden information conditions involved division of coins
      where some coins were only visible to the participant (e.g., 8/2 condition where,
      from the total of 10 coins, 8 coins were visible to both players and 2 coins only
      visible to the proposer). In total, 22 young adults and 79 children between ages
      8 and 13 played multiple one-shot versions of the UG with hidden conditions with
      anonymous others. Overall analyses confirmed validity of the task and showed that
      participants of all age groups had strategic intentions. Specific task analyses
      revealed that adults divided the coins equally in the standard UG conditions, but
      gave less to the second player in the hidden information conditions. The
      developmental comparisons revealed an age * condition interaction, such that
      adults and 10- to 12-year-old children differentiated between standard and hidden
      conditions more than 8- to 9-year-old children. These findings indicate that
      young children have a basic understanding of different strategic motives, but
      that behavior of adults and older children is driven more by strategic
      intentions.

PMID- 23162495
TI  - Oscillatory EEG correlates of arithmetic strategies: a training study.
AB  - There has been a long tradition of research on mathematics education showing that
      children and adults use different strategies to solve arithmetic problems.
      Neurophysiological studies have recently begun to investigate the brain
      correlates of these strategies. The existing body of data, however, reflect
      static end points of the learning process and do not provide information on how
      brain activity changes in response to training or intervention. In this study, we
      explicitly address this issue by training participants in using fact retrieval
      strategies. We also investigate whether brain activity related to arithmetic fact
      learning is domain-specific or whether this generalizes to other learning
      materials, such as the solution of figural-spatial problems. Twenty adult
      students were trained on sets of two-digit multiplication problems and figural
      spatial problems. After the training, they were presented with the trained and
      untrained problems while their brain activity was recorded by means of
      electroencephalography (EEG). In both problem types, the training resulted in
      accuracies over 90% and significant decreases in solution times. Analyses of the
      oscillatory EEG data also revealed training effects across both problem types.
      Specifically, we observed training-related activity increases in the theta band
      (3-6 Hz) and decreases in the lower alpha band (8-10 Hz), especially over
      parietooccipital and parietal brain regions. These results provide the first
      evidence that a short-term fact retrieval training results in significant changes
      in oscillatory EEG activity. These findings further corroborate the role of the
      theta band in the retrieval of semantic information from memory and suggest that
      theta activity is sensitive to fact retrieval not only in mental arithmetic but
      also in other domains.

PMID- 23162496
TI  - A study of theory of mind in paranoid schizophrenia: a theory or many theories?
AB  - Social cognitive psychologists (Frith, 1992; Hardy-Bayle et al., 2003) sought to
      explain the social problems and clarify the clinical picture of schizophrenia by
      proposing a model that relates many of the symptoms to a problem of
      metarepresentation, i.e., theory of mind (ToM). Given the differences in clinical
      samples and results between studies, and considering the wide range of what is
      considered to constitute ToM, one must ask if there a core function, or is ToM
      multifaceted with dissociable facets? If, there are dissociable dimensions or
      facets, which are affected in patients with paranoid schizophrenia? To answer
      these questions, a group of 21 individuals diagnosed with paranoid schizophrenia
      and 29 non-clinical control subjects, were tested on a battery of five different
      measures of ToM. The results confirmed that there was little difference in
      specificity of three of the tests in distinguishing between the clinical and non
      clinical group, but there were important differences in the shared variance
      between the tests. Further analyses hint at two dimensions although a single
      factor with the same variance and the same contributing weights in both groups
      could explain the results. The deficits related to the attribution of cognitive
      and affective states to others inferred from available verbal and non-verbal
      information. Further analyses revealed that incorrect attributions of mental
      states including the attribution of threatening intentions to others, non
      interpretative responses and incomplete answers, depending on the test of ToM.

PMID- 23162498
TI  - The rights and freedoms gradient of health: evidence from a cross-national study.
AB  - This study examined the combined influences of national levels of socioeconomic
      status (SES), social capital, and rights and freedoms on population level
      physical and mental health outcomes. Indicators of mental health were suicide
      rates, alcohol consumption, and tobacco use. Indicators of physical health
      included life expectancy, infant mortality rates, and prevalence of HIV. Using
      pathway analysis on international data from a selected sample of European, North
      American, South American, and South Caucasus countries, similar models for mental
      health and physical health were developed. In the first model, the positive
      effects of SES and social capital on physical health were completely mediated via
      rights and freedoms. In the second model, the positive effect of SES on mental
      health was completely mediated, while the impact of social capital was partially
      mediated through rights and freedoms. We named the models, the "rights and
      freedoms gradient of health" in recognition of this latter construct's crucial
      role in determining both physical and mental health.

PMID- 23162497
TI  - When emotion blinds: a spatiotemporal competition account of emotion-induced
      blindness.
AB  - Emotional visual scenes are such powerful attractors of attention that they can
      disrupt perception of other stimuli that appear soon afterward, an effect known
      as emotion-induced blindness. What mechanisms underlie this impact of emotion on
      perception? Evidence suggests that emotion-induced blindness may be
      distinguishable from closely related phenomena such as the orienting of spatial
      attention to emotional stimuli or the central resource bottlenecks commonly
      associated with the attentional blink. Instead, we suggest that emotion-induced
      blindness reflects relatively early competition between targets and emotional
      distractors, where spontaneous prioritization of emotional stimuli leads to
      suppression of competing perceptual representations potentially linked to an
      overlapping point in time and space.

PMID- 23162500
TI  - Prosodic cues to word order: what level of representation?
AB  - Within language, systematic correlations exist between syntactic structure and
      prosody. Prosodic prominence, for instance, falls on the complement and not the
      head of syntactic phrases, and its realization depends on the phrasal position of
      the prominent element. Thus, in Japanese, a functor-final language, prominence is
      phrase-initial, and realized as increased pitch (^ Tokyoni "Tokyo to"), whereas
      in French, English, or Italian, functor-initial languages, it manifests itself as
      phrase-final lengthening (toRome). Prosody is readily available in the linguistic
      signal even to the youngest infants. It has, therefore, been proposed that young
      learners might be able to exploit its correlations with syntax to bootstrap
      language structure. In this study, we tested this hypothesis, investigating how 8
      month-old monolingual French infants processed an artificial grammar manipulating
      the relative position of prosodic prominence and word frequency. In Condition 1,
      we created a speech stream in which the two cues, prosody and frequency, were
      aligned, frequent words being prosodically non-prominent and infrequent ones
      being prominent, as is the case in natural language (functors are prosodically
      minimal compared to content words). In Condition 2, the two cues were misaligned,
      with frequent words carrying prosodic prominence, unlike in natural language.
      After familiarization with the aligned or the misaligned stream in a headturn
      preference procedure, we tested infants' preference for test items having a
      frequent word initial or a frequent word final word order. We found that infants'
      familiarized with the aligned stream showed the expected preference for the
      frequent word initial test items, mimicking the functor-initial word order of
      French. Infants in the misaligned condition showed no preference. These results
      suggest that infants are able to use word frequency and prosody as early cues to
      word order and they integrate them into a coherent representation.

PMID- 23162499
TI  - Neural systems for cognitive and emotional processing in posttraumatic stress
      disorder.
AB  - Individuals with posttraumatic stress disorder (PTSD) show altered cognition when
      trauma-related material is present. PTSD may lead to enhanced processing of
      trauma-related material, or it may cause impaired processing of trauma-unrelated
      information. However, other forms of emotional information may also alter
      cognition in PTSD. In this review, we discuss the behavioral and neural effects
      of emotion processing on cognition in PTSD, with a focus on neuroimaging results.
      We propose a model of emotion-cognition interaction based on evidence of two
      network models of altered brain activation in PTSD. The first is a trauma
      disrupted network made up of ventrolateral PFC, dorsal anterior cingulate cortex
      (ACC), hippocampus, insula, and dorsomedial PFC that are differentially modulated
      by trauma content relative to emotional trauma-unrelated information. The trauma
      disrupted network forms a subnetwork of regions within a larger, widely
      recognized network organized into ventral and dorsal streams for processing
      emotional and cognitive information that converge in the medial PFC and cingulate
      cortex. Models of fear learning, while not a cognitive process in the
      conventional sense, provide important insights into the maintenance of the core
      symptom clusters of PTSD such as re-experiencing and hypervigilance. Fear
      processing takes place within the limbic corticostriatal loop composed of threat
      alerting and threat-assessing components. Understanding the disruptions in these
      two networks, and their effect on individuals with PTSD, will lead to an improved
      knowledge of the etiopathogenesis of PTSD and potential targets for both
      psychotherapeutic and pharmacotherapeutic interventions.

PMID- 23162501
TI  - From sensorimotor inhibition to freudian repression: insights from psychosis
      applied to neurosis.
AB  - First, three case studies are presented of psychotic patients having in common an
      inability to hold something down or out. In line with other theories on
      psychosis, we propose that a key change is at the efference copy system. Going
      back to Freud's mental apparatus, we propose that the messages of discharge of
      the motor neurons, mobilized to direct perception, also called "indications of
      reality," are equivalent to the modern efference copies. With this key, the
      reading of the cases is coherent with the psychodynamic understanding of
      psychosis, being a downplay of secondary processes, and consequently, a dominance
      of primary processes. Moreover, putting together the sensorimotor idea of a
      failure of efference copy-mediated inhibition with the psychoanalytic idea of a
      failing repression in psychosis, the hypothesis emerges that the attenuation
      enabled by the efference copy dynamics is, in some instances, the physiological
      instantiation of repression. Second, we applied this idea to the mental
      organization in neurosis. Indeed, the efference copy-mediated attenuation is
      thought to be the mechanism through which sustained activation of an intention,
      without reaching it - i.e., inhibition of an action - gives rise to mental
      imagery. Therefore, as inhibition is needed for any targeted action or for normal
      language understanding, acting in the world, or processing language, structurally
      induces mental imagery, constituting a subjective unconscious mental reality.
      Repression is a special instance of inhibition for emotionally threatening
      stimuli. These stimuli require stronger inhibition, leaving (the attenuation of)
      the motor intentions totally unanswered, in order to radically prevent execution
      which would lead to development of excess affect. This inhibition, then, yields a
      specific type of motor imagery, called "phantoms," which induce mental
      preoccupation, as well as symptoms which, especially through their form, refer to
      the repressed motor fragments.

PMID- 23162502
TI  - Markers of deception in italian speech.
AB  - Lying is a universal activity and the detection of lying a universal concern.
      Presently, there is great interest in determining objective measures of
      deception. The examination of speech, in particular, holds promise in this
      regard; yet, most of what we know about the relationship between speech and lying
      is based on the assessment of English speaking participants. Few studies have
      examined indicators of deception in languages other than English. The world's
      languages differ in significant ways, and cross-linguistic studies of deceptive
      communications are a research imperative. Here we review some of these
      differences amongst the world's languages, and provide an overview of a number of
      recent studies demonstrating that cross-linguistic research is a worthwhile
      endeavor. In addition, we report the results of an empirical investigation of
      pitch, response latency, and speech rate as cues to deception in Italian speech.
      True and false opinions were elicited in an audio-taped interview. A within
      subjects analysis revealed no significant difference between the average pitch of
      the two conditions; however, speech rate was significantly slower, while response
      latency was longer, during deception compared with truth-telling. We explore the
      implications of these findings and propose directions for future research, with
      the aim of expanding the cross-linguistic branch of research on markers of
      deception.

PMID- 23162503
TI  - How Fast is Famous Face Recognition?
AB  - The rapid recognition of familiar faces is crucial for social interactions.
      However the actual speed with which recognition can be achieved remains largely
      unknown as most studies have been carried out without any speed constraints.
      Different paradigms have been used, leading to conflicting results, and although
      many authors suggest that face recognition is fast, the speed of face recognition
      has not been directly compared to "fast" visual tasks. In this study, we sought
      to overcome these limitations. Subjects performed three tasks, a familiarity
      categorization task (famous faces among unknown faces), a superordinate
      categorization task (human faces among animal ones), and a gender categorization
      task. All tasks were performed under speed constraints. The results show that,
      despite the use of speed constraints, subjects were slow when they had to
      categorize famous faces: minimum reaction time was 467 ms, which is 180 ms more
      than during superordinate categorization and 160 ms more than in the gender
      condition. Our results are compatible with a hierarchy of face processing from
      the superordinate level to the familiarity level. The processes taking place
      between detection and recognition need to be investigated in detail.

PMID- 23162504
TI  - Intention concepts and brain-machine interfacing.
AB  - Intentions, including their temporal properties and semantic content, are
      receiving increased attention, and neuroscientific studies in humans vary with
      respect to the topography of intention-related neural responses. This may reflect
      the fact that the kind of intentions investigated in one study may not be exactly
      the same kind investigated in the other. Fine-grained intention taxonomies
      developed in the philosophy of mind may be useful to identify the neural
      correlates of well-defined types of intentions, as well as to disentangle them
      from other related mental states, such as mere urges to perform an action.
      Intention-related neural signals may be exploited by brain-machine interfaces
      (BMIs) that are currently being developed to restore speech and motor control in
      paralyzed patients. Such BMI devices record the brain activity of the agent,
      interpret ("decode") the agent's intended action, and send the corresponding
      execution command to an artificial effector system, e.g., a computer cursor or a
      robotic arm. In the present paper, we evaluate the potential of intention
      concepts from philosophy of mind to improve the performance and safety of BMIs
      based on higher-order, intention-related control signals. To this end, we address
      the distinction between future-, present-directed, and motor intentions, as well
      as the organization of intentions in time, specifically to what extent it is
      sequential or hierarchical. This has consequences as to whether these different
      types of intentions can be expected to occur simultaneously or not. We further
      illustrate how it may be useful or even necessary to distinguish types of
      intentions exposited in philosophy, including yes- vs. no-intentions and oblique
      vs. direct intentions, to accurately decode the agent's intentions from neural
      signals in practical BMI applications.

PMID- 23162505
TI  - Identifying sources of configurality in three face processing tasks.
AB  - Participants performed three feature-complete face processing tasks involving
      detection of changes in: (1) feature size and (2) feature identity in successive
      matching tasks, and (3) feature orientation. In each experiment, information in
      the top (eyes) and bottom (mouths) parts of faces were manipulated. All tasks
      were performed with upright and inverted faces. Data were analyzed first using
      group-based analysis of signal detection measures (sensitivity and bias), and
      second using analysis of multidimensional measures of sensitivity and bias along
      with probit regression models in order to draw inferences about independence and
      separability as defined within general recognition theory (Ashby and Townsend,
      1986). The results highlighted different patterns of perceptual and decisional
      influences across tasks and orientations. There was evidence of orientation
      specific configural effects (violations of perceptual independence, perceptual
      seperability and decisional separabilty) in the Feature Orientation Task. For the
      Feature Identity Task there were orientation specific performance effects and
      there was evidence of configural effects (violations of decisional separability)
      in both orientations. Decisional effects are consistent with previous research
      (Wenger and Ingvalson, 2002, 2003; Richler et al., 2008; Cornes et al., 2011).
      Crucially, the probit analysis revealed violations of perceptual independence
      that remain undetected by marginal analysis.

PMID- 23162506
TI  - Reading the World through the Skin and Ears: A New Perspective on Sensory
      Substitution.
AB  - Sensory substitution devices aim at replacing or assisting one or several
      functions of a deficient sensory modality by means of another sensory modality.
      Despite the numerous studies and research programs devoted to their development
      and integration, sensory substitution devices have failed to live up to their
      goal of allowing one to "see with the skin" (White et al., 1970) or to "see with
      the brain" (Bach-y-Rita et al., 2003). These somewhat peremptory claims, as well
      as the research conducted so far, are based on an implicit perceptual paradigm.
      Such perceptual assumption accepts the equivalence between using a sensory
      substitution device and perceiving through a particular sensory modality. Our aim
      is to provide an alternative model, which defines sensory substitution as being
      closer to culturally implemented cognitive extensions of existing perceptual
      skills such as reading. In this article, we will show why the analogy with
      reading provides a better explanation of the actual findings, that is, both of
      the positive results achieved and of the limitations noticed across the field of
      research on sensory substitution. The parallel with the most recent two-route and
      interactive models of reading (e.g., Dehaene et al., 2005) generates a radically
      new way of approaching these results, by stressing the dependence of integration
      on the existing perceptual-semantic route. In addition, the present perspective
      enables us to generate innovative research questions and specific predictions
      which set the stage for future work.

PMID- 23162507
TI  - Duration judgments over multiple elements.
AB  - We investigated the limits of the number of events observers can simultaneously
      time. For single targets occurring in one of eight positions sensitivity to
      duration was improved for spatially pre-cued items as compared to post-cued items
      indicating that exogenous driven attention can improve duration discrimination.
      Sensitivity to duration for pre-cued items was also marginally better for single
      items as compared to eight items indicating that even after the allocation of
      focal attention, distractor items can interfere with the encoding of duration.
      For an eight item array discrimination was worse for post-cued locations as
      compared to pre-cued locations indicating both that attention can improve
      duration discrimination performance and that it was not possible to access a
      perfect memory trace of the duration of eight elements. The interference from the
      distractors in the pre-cued eight item array may reflect some mandatory averaging
      of target and distractor events. To further explore duration averaging we asked
      subjects to explicitly compare average durations of multiple item arrays against
      a single item standard duration. Duration discrimination thresholds were
      significantly lower for single elements as compared to multiple elements, showing
      that averaging, either automatically or intentionally, impairs duration
      discrimination. There was no set size effect. Performance was the same for
      averages of two and eight items, but performance with even an average of two
      items was worse than for one item. This was also true for sequential presentation
      indicating poor performance was not due to limits on the division of attention
      across items. Rather performance appears to be limited by an inability to
      remember or aggregate duration information from two or more items. Although it is
      possible to manipulate perceived duration locally, there appears to be no
      perceptual mechanisms for aggregating local durations across space.

PMID- 23162508
TI  - Assessing evidence for a common function of delay in causal learning and reward
      discounting.
AB  - Time occupies a central role in both the induction of causal relationships and
      determining the subjective value of rewards. Delays devalue rewards and also
      impair learning of relationships between events. The mathematical relation
      between the time until a delayed reward and its present value has been
      characterized as a hyperbola-like function, and increasing delays of
      reinforcement tend to elicit judgments or response rates that similarly show a
      negatively accelerated decay pattern. Furthermore, neurological research
      implicates both the hippocampus and prefrontal cortex in both these processes.
      Since both processes are broadly concerned with the concepts of reward, value,
      and time, involve a similar functional form, and have been identified as
      involving the same specific brain regions, it seems tempting to assume that the
      two processes are underpinned by the same cognitive or neural mechanisms. We set
      out to determine experimentally whether a common cognitive mechanism underlies
      these processes, by contrasting individual performances on causal judgment and
      delay discounting tasks. Results from each task corresponded with previous
      findings in the literature, but no relation was found between the two tasks. The
      task was replicated and extended by including two further measures, the Barrett
      Impulsiveness Scale (BIS), and a causal attribution task. Performance on this
      latter task was correlated with results on the causal judgment task, and also
      with the non-planning component of the BIS, but the results from the delay
      discounting task was not correlated with either causal learning task nor the BIS.
      Implications for current theories of learning are considered.

PMID- 23162509
TI  - Spatial frequency integration during active perception: perceptual hysteresis
      when an object recedes.
AB  - As we move through the world, information about objects moves to different
      spatial frequencies. How the visual system successfully integrates information
      across these changes to form a coherent percept is thus an important open
      question. Here we investigate such integration using hybrid faces, which contain
      different images in low and high spatial frequencies. Observers judged how
      similar a hybrid was to each of its component images while walking toward or away
      from it or having the stimulus moved toward or away from them. We find that when
      the stimulus is approaching, observers act as if they are integrating across
      spatial frequency separately at each moment. However, when the stimulus is
      receding, observers show a perceptual hysteresis effect, holding on to details
      that are imperceptible in a static stimulus condition. Thus, observers appear to
      make optimal inferences by sticking with their previous interpretation when
      losing information but constantly reinterpreting their input when gaining new
      information.

PMID- 23162510
TI  - Efficacy of hypnosis-based treatment in amyotrophic lateral sclerosis: a pilot
      study.
AB  - BACKGROUND: Amyotrophic lateral sclerosis (ALS) and its devastating
      neurodegenerative consequences have an inevitably psychological impact on
      patients and their caregivers: however, although it would be strongly needed,
      there is a lack of research on the efficacy of psychological intervention. Our
      aim was to investigate the effect of hypnosis-based intervention on psychological
      and perceived physical wellbeing in patients and the indirect effect on
      caregivers. METHODS: We recruited eight ALS volunteers patients as a pilot sample
      for an hypnosis intervention and self-hypnosis training protocol lasting 1 month.
      Anxiety and depression level was measured in patients and caregivers at pre and
      post treatment phase. Quality of life and perceived physical symptoms changes
      were also investigated in patients. RESULTS: One month pre-post treatment
      improvement in depression, anxiety, and quality of life was clearly clinically
      observed and confirmed by psychometric analyses on questionnaire data. Moreover,
      decreases in physical symptoms such as pain, sleep disorders, emotional lability,
      and fasciculations were reported by our patients. Improvements in caregiver
      psychological wellbeing, likely as a consequence of patients psychological and
      perceived physical symptomatology improvement, were also observed. CONCLUSION: To
      the best of our knowledge, even if at a preliminary level, this is the first
      report on efficacy psychological intervention protocol on ALS patients. The
      findings provide initial support for using hypnosis and self-hypnosis training to
      manage some ALS physical consequences and mainly to cope its dramatic
      psychological implications for patients and, indirectly, for their caregivers.

PMID- 23162511
TI  - Effects of peripheral visual field loss on eye movements during visual search.
AB  - Natural vision involves sequential eye movements that bring the fovea to
      locations selected by peripheral vision. How peripheral visual field loss (PVFL)
      affects this process is not well understood. We examine how the location and
      extent of PVFL affects eye movement behavior in a naturalistic visual search
      task. Ten patients with PVFL and 13 normally sighted subjects with full visual
      fields (FVF) completed 30 visual searches monocularly. Subjects located a 4
      degrees  * 4 degrees  target, pseudo-randomly selected within a 26 degrees  * 11
      degrees  natural image. Eye positions were recorded at 50 Hz. Search duration,
      fixation duration, saccade size, and number of saccades per trial were not
      significantly different between PVFL and FVF groups (p > 0.1). A chi(2) test
      showed that the distributions of saccade directions for PVFL and FVL subjects
      were significantly different in 8 out of 10 cases (p < 0.01). Humphrey Visual
      Field pattern deviations for each subject were compared with the spatial
      distribution of eye movement directions. There were no significant correlations
      between saccade directional bias and visual field sensitivity across the 10
      patients. Visual search performance was not significantly affected by PVFL. An
      analysis of eye movement directions revealed patients with PVFL show a biased
      directional distribution that was not directly related to the locus of vision
      loss, challenging feed-forward models of eye movement control. Consequently, many
      patients do not optimally compensate for visual field loss during visual search.

PMID- 23162512
TI  - Evidence for a Numerosity Category that is Based on Abstract Qualities of "Few"
      vs. "Many" in the Bottlenose Dolphin (Tursiops truncatus).
AB  - A previous study (Kilian et al., 2003) had demonstrated that bottlenose dolphins
      can discriminate visual stimuli differing in numerosity. The aim of the present
      study was twofold: first, we sought to determine if dolphins are able to use a
      numerical category based on "few" vs. "many" when discriminating stimuli
      according to the number of their constituent patterns. Second, we aimed to extend
      the previously demonstrated range of numbers, thereby testing the limits of the
      numerical abilities of bottlenose dolphins. To this end, one adult bottlenose
      dolphin learned to discriminate between two simultaneously presented stimuli
      which varied in the number of elements they contained. After initial training,
      several confounding parameters were excluded to render it likely that
      discrimination performance indeed depended on numerosity. Subsequently, the
      animal was tested with new stimuli of intermediate as well as higher numbers of
      elements. Once discrimination had been achieved, a reversal-training on a subset
      of stimuli was initiated. Afterward, the subject generalized the reversal
      successful to new and unreinforced stimuli. Our results reveal two main findings:
      firstly, our data strongly suggest a magnitude and a distance effect. Thus,
      coding of numerical information in dolphins might follow logarithmic scaling as
      postulated by the Weber-Fechner law. Secondly, after learning a reversal of
      contingencies, the dolphin generalized the reversal successful to new and
      unreinforced stimuli. Thus, within the limits of a study that was conducted with
      a single individual, our results suggest that dolphins are able to learn and use
      a numerical category that is based on abstract qualities of "few" vs. "many."

PMID- 23162514
TI  - Does imitation facilitate word recognition in a non-native regional accent?
AB  - We asked to what extent phonetic convergence across speakers may facilitate later
      word recognition. Northern-French participants showed both a clear phonetic
      convergence effect toward Southern French in a word repetition task, and a bias
      toward the phonemic system of their own variety in the recognition of single
      words. Perceptual adaptation to a non-native accent may be difficult when the
      native accent has a phonemic contrast that is associated with a single phonemic
      category in the non-native accent. Convergence toward a speaker of a non-native
      accent in production may not prevent each speaker's native variety to prevail in
      word identification. Imitation has been found in previous studies to contribute
      to predicting upcoming words in sentences in adverse listening conditions, but
      may play a more limited role in the recognition of single words.

PMID- 23162513
TI  - Linguistic processing of accented speech across the lifespan.
AB  - In most of the world, people have regular exposure to multiple accents.
      Therefore, learning to quickly process accented speech is a prerequisite to
      successful communication. In this paper, we examine work on the perception of
      accented speech across the lifespan, from early infancy to late adulthood.
      Unfamiliar accents initially impair linguistic processing by infants, children,
      younger adults, and older adults, but listeners of all ages come to adapt to
      accented speech. Emergent research also goes beyond these perceptual abilities,
      by assessing links with production and the relative contributions of linguistic
      knowledge and general cognitive skills. We conclude by underlining points of
      convergence across ages, and the gaps left to face in future work.

PMID- 23162515
TI  - Incremental Phonological Encoding during Unscripted Sentence Production.
AB  - We investigate phonological encoding during unscripted sentence production,
      focusing on the effect of phonological overlap on phonological encoding. Previous
      work on this question has almost exclusively employed isolated word production or
      highly scripted multi-word production. These studies have led to conflicting
      results: some studies found that phonological overlap between two words
      facilitates phonological encoding, while others found inhibitory effects. One
      worry with many of these paradigms is that they involve processes that are not
      typical to everyday language use, which calls into question to what extent their
      findings speak to the architectures and mechanisms underlying language
      production. We present a paradigm to investigate the consequences of phonological
      overlap between words in a sentence while leaving speakers much of the lexical
      and structural choices typical in everyday language use. Adult native speakers of
      English described events in short video clips. We annotated the presence of
      disfluencies and the speech rate at various points throughout the sentence, as
      well as the constituent order. We find that phonological overlap has an
      inhibitory effect on phonological encoding. Specifically, if adjacent content
      words share their phonological onset (e.g., hand the hammer), they are preceded
      by production difficulty, as reflected in fluency and speech rate. We also find
      that this production difficulty affects speakers' constituent order preferences
      during grammatical encoding. We discuss our results and previous works to isolate
      the properties of other paradigms that resulted in facilitatory or inhibitory
      results. The data from our paradigm also speak to questions about the scope of
      phonological planning in unscripted speech and as to whether phonological and
      grammatical encoding interact.

PMID- 23162516
TI  - Effects of empathic paraphrasing - extrinsic emotion regulation in social
      conflict.
AB  - In the present study, we investigated the effects of empathic paraphrasing as an
      extrinsic emotion regulation technique in social conflict. We hypothesized that
      negative emotions elicited by social conflict can be regulated extrinsically in a
      conversation by a listener following the narrator's perspective and verbally
      expressing cognitive empathy. Twenty participants were interviewed on an ongoing
      or recently self-experienced social conflict. The interviewer utilized 10
      standardized open questions inviting participants to describe their perception of
      the conflict. After each of the 10 descriptions, the interviewer responded by
      either paraphrasing or taking notes (control condition). Valence ratings
      pertaining to the current emotional state were assessed during the interview
      along with psychophysiological and voice recordings. Participants reported
      feeling less negative after hearing the interviewer paraphrase what they had
      said. In addition, we found a lower sound intensity of participants' voices when
      answering to questions following a paraphrase. At the physiological level, skin
      conductance response, as well as heart rate, were higher during paraphrasing than
      during taking notes, while blood volume pulse amplitude was lower during
      paraphrasing, indicating higher autonomic arousal. The results show that
      demonstrating cognitive empathy through paraphrasing can extrinsically regulate
      negative emotion on a short-term basis. Paraphrasing led to enhanced autonomic
      activation in recipients, while at the same time influencing emotional valence in
      the direction of feeling better. A possible explanation for these results is that
      being treated in an empathic manner may stimulate a more intense emotion
      processing helping to transform and resolve the conflict.

PMID- 23162517
TI  - Inter-specific differences in numerical abilities among teleost fish.
AB  - Adults, infants and non-human primates are thought to possess similar non-verbal
      numerical systems, but there is considerable debate regarding whether all
      vertebrates share the same numerical abilities. Despite an abundance of studies,
      cross-species comparison remains difficult because the methodology employed and
      the context of species examination vary considerably across studies. To fill this
      gap, we used the same procedure, stimuli, and numerical contrasts to compare
      quantity abilities of five teleost fish: redtail splitfin, guppies, zebrafish,
      Siamese fighting fish, and angelfish. Subjects were trained to discriminate
      between two sets of geometrical figures using a food reward. Fish initially were
      trained on an easy numerical ratio (5 vs. 10 and 6 vs. 12). Once they reached the
      learning criterion, they were subjected to non-reinforced probe trials in which
      the set size was constant but numerical ratios varied (8 vs. 12 and 9 vs. 12).
      They also were subjected to probe trials in which the ratio was constant, but the
      total set size was increased (25 vs. 50) or decreased (2 vs. 4). Overall, fish
      generalized to numerosities with a 0.67 ratio, but failed with a 0.75 ratio; they
      generalized to a smaller set size, but not to a larger one. Only minor
      differences were observed among the five species. However, in one species,
      zebrafish, the proportion of individuals reaching the learning criterion was much
      smaller than in the others. In a control experiment, zebrafish showed a similar
      lower performance in shape discrimination, suggesting that the observed
      difference resulted from the zebrafish's difficulty in learning this procedure
      rather than from a cross-species variation in the numerical domain.

PMID- 23162518
TI  - Activity counts: the effect of swimming activity on quantity discrimination in
      fish.
AB  - Human infants and non-human animals can discriminate the larger of two sets of
      discrete items. This quantity discrimination may be based upon the number of
      items, or upon non-numerical variables of the sets that co-vary with number. We
      have demonstrated that angelfish select the larger of two shoals of conspecifics
      without using inter-fish distance or space occupied by the stimuli as cues.
      However, density appeared to influence the choice between large shoals. Here, we
      examine the role of another non-numerical cue, swimming activity of the stimulus
      fish, in quantity discrimination by angelfish. To control this variable, we
      varied the water temperature of the stimulus aquaria or restricted the space
      occupied by each fish in the stimulus shoals. We used the previously successfully
      discriminated contrasts consisting of large (10 vs. 5) and small (3 vs. 2)
      shoals. We also studied whether more active or less active shoals are preferred
      in case of equally sized shoals (10 vs. 10, 5 vs. 5, and 3 vs. 3). When
      differences in stimulus fish activity were minimized by temperature manipulation
      we found angelfish to prefer the larger shoal in the 3 vs. 2 comparison, but not
      in the 10 vs. 5 comparison. When activity was controlled by space restriction,
      angelfish preferred the larger shoal in both numerical contrasts. These results
      imply that the overall activity level of the contrasted shoals is not a necessary
      condition for small shoals discrimination in angelfish. On the other hand, the
      results obtained for the large shoals, together with results obtained in the
      control treatments (equal numerical contrasts and differing activity levels),
      suggest that activity is a sufficient condition for discrimination when large
      shoals are involved. Further experiments are needed to evaluate the influence of
      other continuous variables, and to assess whether the mechanisms underlying
      performance are comparable to those suggested for other animals.

PMID- 23162519
TI  - Moving Forward in Space and Time: How Strong is the Conceptual Link between
      Spatial and Temporal Frames of Reference?
AB  - People often use spatial vocabulary to describe temporal relations, and this
      increasingly has motivated attempts to map spatial frames of reference (FoRs)
      onto time. Recent research suggested that speech communities, which differ in how
      they conceptualize space, may also differ in how they conceptualize time and,
      more specifically, that the preferences for spatial FoRs should carry over to the
      domain of time. Here, we scrutinize this assumption (a) by reviewing data from
      recent studies on temporal references, (b) by comparing data we had collected in
      previous studies on preferences for spatial and temporal FoRs in four languages,
      (c) by analyzing new data from dynamic spatial tasks that resemble the temporal
      tasks more closely, and (d) by assessing the co-variation of individual
      preferences of English speakers across space and time. While the first set of
      data paints a mixed picture, the latter three do not support the assumption of a
      close link between referencing preferences across domains. We explore possible
      reasons for this lack of consistency and discuss implications for research on
      temporal references.

PMID- 23162520
TI  - A repeated lie becomes a truth? The effect of intentional control and training on
      deception.
AB  - Deception has been demonstrated as a task that involves executive control such as
      conflict monitoring and response inhibition. In the present study, we
      investigated whether or not the controlled processes associated with deception
      could be trained to be more efficient. Forty-eight participants finished a
      reaction time-based differentiation of deception paradigm (DDP) task using self-
      and other-referential information on two occasions. After the first baseline DDP
      task, participants were randomly assigned to one of three groups: a control group
      in which participants finished the same task for a second time; an instruction
      group in which participants were instructed to speed up their deceptive responses
      in the second DDP; a training group in which participants received training in
      speeding up their deceptive responses, and then proceeded to the second DDP.
      Results showed that instruction alone significantly reduced the RTs associated
      with participants' deceptive responses. However, the differences between
      deceptive and truthful responses were erased only in the training group. The
      result suggests that the performance associated with deception is malleable and
      could be voluntarily controlled with intention or training.

PMID- 23162522
TI  - Near-Death-Like Experiences without Life-Threatening Conditions or Brain
      Disorders: A Hypothesis from a Case Report.
AB  - Near-death experiences (NDEs) are profound psychic experiences commonly occurring
      in life-threatening conditions. They include feeling a sense of peace, of seeing
      a bright light, encountering deceased relatives or religious figures, and of
      transcending space and time. To explain them, it has been suggested that they
      stem from brain disorders and/or psychological reactions to approaching death, a
      sort of wishful thinking in response to the perceived threat. This is a report on
      a case with most of the features typical of NDEs except that it occurred entirely
      without any life-threatening conditions. This evidence is theoretically
      incompatible with either of the above hypotheses, suggesting that a broader
      interpretation of the phenomenon is needed.

PMID- 23162521
TI  - Cognitive and neural aspects of information processing in major depressive
      disorder: an integrative perspective.
AB  - Researchers using experimental paradigms to examine cognitive processes have
      demonstrated that Major Depressive Disorder (MDD) is associated not with a
      general deficit in cognitive functioning, but instead with more specific
      anomalies in the processing of negatively valenced material. Indeed, cognitive
      theories of depression posit that negative biases in the processing of
      information play a critical role in influencing the onset, maintenance, and
      recurrence of depressive episodes. In this paper we review findings from
      behavioral studies documenting that MDD is associated with specific difficulties
      in attentional disengagement from negatively valenced material, with tendencies
      to interpret information in a negative manner, with deficits in cognitive control
      in the processing of negative material, and with enhanced memory for negative
      material. To gain a better understanding of the neurobiological basis of these
      abnormalities, we also examine findings from functional neuroimaging studies of
      depression and show that dysfunction in neural systems that subserve emotion
      processing, inhibition, and attention may underlie and contribute to the deficits
      in cognition that have been documented in depressed individuals. Finally, we
      briefly review evidence from studies of children who are at high familial risk
      for depression that indicates that abnormalities in cognition and neural function
      are observable before the onset of MDD and, consequently, may represent a risk
      factor for the development of this disorder. By integrating research from
      cognitive and neural investigations of depression, we can gain a more
      comprehensive understanding not only of how cognitive and biological factors
      interact to affect the onset, maintenance, and course of MDD, but also of how
      such research can aid in the development of targeted strategies for the
      prevention and treatment of this debilitating disorder.

PMID- 23162523
TI  - Inhibition in the dynamics of selective attention: an integrative model for
      negative priming.
AB  - We introduce a computational model of the negative priming (NP) effect that
      includes perception, memory, attention, decision making, and action. The model is
      designed to provide a coherent picture across competing theories of NP. The model
      is formulated in terms of abstract dynamics for the activations of features,
      their binding into object entities, their semantic categorization as well as
      related memories and appropriate reactions. The dynamic variables interact in a
      connectionist network which is shown to be adaptable to a variety of experimental
      paradigms. We find that selective attention can be modeled by means of inhibitory
      processes and by a threshold dynamics. From the necessity of quantifying the
      experimental paradigms, we conclude that the specificity of the experimental
      paradigm must be taken into account when predicting the nature of the NP effect.

PMID- 23162525
TI  - Reductio ad bacterium: the ubiquity of Bayesian "brains" and the goals of
      cognitive science.

PMID- 23162524
TI  - Too Good to be True? Ideomotor Theory from a Computational Perspective.
AB  - In recent years, Ideomotor Theory has regained widespread attention and sparked
      the development of a number of theories on goal-directed behavior and learning.
      However, there are two issues with previous studies' use of Ideomotor Theory.
      Although Ideomotor Theory is seen as very general, it is often studied in
      settings that are considerably more simplistic than most natural situations.
      Moreover, Ideomotor Theory's claim that effect anticipations directly trigger
      actions and that action-effect learning is based on the formation of direct
      action-effect associations is hard to address empirically. We address these
      points from a computational perspective. A simple computational model of
      Ideomotor Theory was tested in tasks with different degrees of complexity. The
      model evaluation showed that Ideomotor Theory is a computationally feasible
      approach for understanding efficient action-effect learning for goal-directed
      behavior if the following preconditions are met: (1) The range of potential
      actions and effects has to be restricted. (2) Effects have to follow actions
      within a short time window. (3) Actions have to be simple and may not require
      sequencing. The first two preconditions also limit human performance and thus
      support Ideomotor Theory. The last precondition can be circumvented by extending
      the model with more complex, indirect action generation processes. In conclusion,
      we suggest that Ideomotor Theory offers a comprehensive framework to understand
      action-effect learning. However, we also suggest that additional processes may
      mediate the conversion of effect anticipations into actions in many situations.

PMID- 23162526
TI  - Bayes or determinables? What does the bidirectional hierarchical model of brain
      functions tell us about the nature of perceptual representation?

PMID- 23162527
TI  - Systematic review of teleneurology: methodology.
AB  - BACKGROUND: The use of two-way audio-visual technology for delivery of acute
      stroke is supported by a well established literature base. The use of
      telemedicine for general neurologic consultation has been reported across most
      subspecialties within the field, but a comprehensive systematic review of these
      reports is lacking. PURPOSE: To conduct a systematic review of the published
      literature on teleneurologic consultation beyond stroke. DATA SOURCES: Databases
      Ovid MEDLINE, EMBASE, PsychINFO, CINAHL, and Cochrane were searched with
      keywords, "teleneurology," and numerous synonyms and cross-referenced with
      neurology subspecialties. The search yielded 6,615 potentially eligible hits,
      which were independently reviewed by two investigators. Ultimately 375 unique
      studies met eligibility criteria and were included in the review. STUDY
      SELECTION: Studies were included if the title or abstract expressed use of two
      way AV communication for a clinical neurologic indication other than stroke. DATA
      EXTRACTION: Each article was classified using a novel scoring rubric to assess
      the level of functionality, application, technology, and evaluative stage. DATA
      ANALYSIS: Articles were hierarchized within a subspecialty category. Overall
      subspecialty scores were assigned based on aggregate of scores across papers in
      each category. CONCLUSION: Use of telemedicine for general and most subspecialty
      neurologic consultation, beyond stroke, appears very promising but the clinical
      science is nascent.

PMID- 23162528
TI  - Using mobile phones for activity recognition in Parkinson's patients.
AB  - Mobile phones with built-in accelerometers promise a convenient, objective way to
      quantify everyday movements and classify those movements into activities. Using
      accelerometer data we estimate the following activities of 18 healthy subjects
      and eight patients with Parkinson's disease: walking, standing, sitting, holding,
      or not wearing the phone. We use standard machine learning classifiers (support
      vector machines, regularized logistic regression) to automatically select, weigh,
      and combine a large set of standard features for time series analysis. Using
      cross validation across all samples we are able to correctly identify 96.1% of
      the activities of healthy subjects and 92.2% of the activities of Parkinson's
      patients. However, when applying the classification parameters derived from the
      set of healthy subjects to Parkinson's patients, the percent correct lowers to
      60.3%, due to different characteristics of movement. For a fairer comparison
      across populations we also applied subject-wise cross validation, identifying
      healthy subject activities with 86.0% accuracy and 75.1% accuracy for patients.
      We discuss the key differences between these populations, and why algorithms
      designed for and trained with healthy subject data are not reliable for activity
      recognition in populations with motor disabilities.

PMID- 23162530
TI  - Plasma Norepinephrine in Hypertensive Rats Reflects alpha(2)-Adrenoceptor Release
      Control Only When Re-Uptake is Inhibited.
AB  - alpha(2)-adrenoceptors (AR) lower central sympathetic output and peripheral
      catecholamine release, thereby protecting against sympathetic hyperactivity and
      hypertension. Norepinephrine re-uptake-transporter effectively (NET) removes
      norepinephrine from the synapse. Overflow to plasma will therefore not reflect
      release. Here we tested if inhibition of re-uptake allowed presynaptic alpha(2)AR
      release control to be reflected as differences in norepinephrine overflow in
      anesthetized hypertensive spontaneously hypertensive rats (SHR) and normotensive
      rats (WKY). We also tested if alpha(2)AR modulated the experiment-induced
      epinephrine secretion, and a phenylephrine-induced, alpha(1)-adrenergic
      vasoconstriction. Blood pressure was recorded through a femoral artery catheter,
      and cardiac output by ascending aorta flow. After pre-treatment with NET
      inhibitor (desipramine), and/or alpha(2)AR antagonist (yohimbine, L-659,066) or
      agonist (clonidine, ST-91), we injected phenylephrine. Arterial blood was sampled
      15 min later. Plasma catecholamine concentrations were not influenced by
      phenylephrine, and therefore reflected effects of pre-treatment. Desipramine and
      alpha(2)AR antagonist separately had little effect on norepinephrine overflow.
      Combined, they increased norepinephrine overflow, particularly in SHR. Clonidine,
      but not ST-91, reduced, and pertussis toxin increased norepinephrine overflow in
      SHR and epinephrine secretion in both strains. L-659,066 + clonidine (central
      alpha(2)AR-stimulation) normalized the high blood pressure, heart rate, and
      vascular tension in SHR. alpha(2)AR antagonists reduced phenylephrine-induced
      vasoconstriction equally in WKY and SHR. CONCLUSIONS: alpha(2A)AR inhibition
      increased norepinephrine overflow only when re-uptake was blocked, and then with
      particular efficacy in SHR, possibly due to their high sympathetic tone.
      alpha(2A)AR inhibited epinephrine secretion, particularly in SHR. alpha(2A)AR
      supported alpha(1)AR-induced vasoconstriction equally in the two strains.
      alpha(2)AR malfunctions were therefore not detected in SHR under this basal
      condition.

PMID- 23162531
TI  - False-positive head-impulse test in cerebellar ataxia.
AB  - The objective of this study was to compare the findings of the bedside head
      impulse test (HIT), passive head rotation gain, and caloric irrigation in
      patients with cerebellar ataxia (CA). In 16 patients with CA and bilaterally
      pathological bedside HIT, vestibuloocular reflex (VOR) gains were measured during
      HIT and passive head rotation by scleral search coil technique. Eight of the
      patients had pathologically reduced caloric responsiveness, while the other eight
      had normal caloric responses. Those with normal calorics showed a slightly
      reduced HIT gain (mean +/- SD: 0.73 +/- 0.15). In those with pathological
      calorics, gains 80 and 100 ms after the HIT as well as the passive rotation VOR
      gains were significantly lower. The corrective saccade after head turn occurred
      earlier in patients with pathological calorics (111 +/- 62 ms after onset of the
      HIT) than in those with normal calorics (191 +/- 17 ms, p = 0.0064). We
      identified two groups of patients with CA: those with an isolated moderate HIT
      deficit only, probably due to floccular dysfunction, and those with combined HIT,
      passive rotation, and caloric deficit, probably due to a peripheral vestibular
      deficit. From a clinical point of view, these results show that the bedside HIT
      alone can be false-positive for establishing a diagnosis of a bilateral
      peripheral vestibular deficit in patients with CA.

PMID- 23162529
TI  - The epidemiology and clinical manifestations of dysexecutive syndrome in
      Parkinson's disease.
AB  - This mini-review summarizes the evidence of the cognitive and behavioral features
      of dysexecutive syndrome in Parkinson's disease (PD). Deficits in response
      inhibition, set-shifting, mental flexibility, and strategy have been frequently
      described from the earliest stages of PD, although there are inconsistencies in
      study findings due to the complexity of the executive function (EF) construct and
      methodological limitations. Behavioral disorders of PD, e.g., apathy,
      distractibility, perseverative behavior, and impulse-control disorders, may be
      viewed as the other side of dysexecutive syndrome. Despite the interrelationship
      between the cognitive and behavioral domains, some reports reveal that the two
      syndromes may be dissociated, suggesting that both aspects must be clinically
      assessed. EFs are widely associated with the prefrontal areas, although
      dysexecutive syndrome may be observed in patients with damage to other brain
      regions. EFs drive numerous abilities essential to daily life, such as
      prospective remembering and language comprehension, which may be impaired in PD
      subjects. Considering the impact of dysexecutive syndrome on independence and
      quality of life, early detection of executive impairment is crucial in the
      management of PD.

PMID- 23162533
TI  - Role of vitamin D on cancer immunotherapy.

PMID- 23162532
TI  - Role of SST, CORT and ghrelin and its receptors at the endocrine pancreas.
AB  - Somatostatin (SST), cortistatin (CORT), and its receptors (sst1-5), and ghrelin
      and its receptors (GHS-R) are two highly interrelated neuropeptide systems with a
      broad range of overlapping biological actions at central, cardiovascular, and
      immune levels among others. Besides their potent regulatory role on GH release,
      its endocrine actions are highlighted by SST/CORT and ghrelin influence on
      insulin secretion, glucose homeostasis, and insulin resistance. Interestingly,
      most components of these systems are expressed at the endocrine pancreas and are
      actively involved in the modulation of pancreatic islet function and,
      consequently influence glucose homeostasis. In addition, some of them also
      participate in islet survival and regeneration. Furthermore, under severe
      metabolic condition as well as in endocrine pathologies, their expression profile
      is severely deregulated. These findings suggest that SST/CORT and ghrelin systems
      could play a relevant role in pancreatic function under metabolic and endocrine
      pathologies. Accordingly, these systems have been therapeutically targeted for
      the prevention or amelioration of certain metabolic conditions (obesity) as well
      as for tumor growth inhibition and/or hormonal regulation in endocrine
      pathologies (neuroendocrine tumors). This review focuses on the interrelationship
      between SST/CORT and ghrelin systems and their role in severe metabolic
      conditions and some endocrine disorders.

PMID- 23162534
TI  - Thyroid cancer cell lines: an overview.
AB  - Human thyroid cancer cell lines are the most used models for thyroid cancer
      studies. They must be used with detailed knowledge of their characteristics.
      These in vitro cell lines originate from differentiated and dedifferentiated in
      vivo human thyroid tumors. However, it has been shown that mRNA expression
      profiles of these cell lines were closer to dedifferentiated in vivo thyroid
      tumors (anaplastic thyroid carcinoma, ATC) than to differentiated ones. Here an
      overview of the knowledge of these models was made. The mutational status of six
      human thyroid cancer cell lines (WRO, FTC133, BCPAP, TPC1, K1, and 8505C) was in
      line with previously reported findings for 10 genes frequently mutated in thyroid
      cancer. However, the presence of a BRAF mutation (T1799A: V600E) in WRO questions
      the use of this cell line as a model for follicular thyroid carcinoma (FTC).
      Next, to investigate the biological meaning of the modulated mRNAs in these
      cells, a pathway analysis on previously obtained mRNA profiles was performed on
      five cell lines. In five cell lines, the MHC class II pathway was down-regulated
      and in four of them, ribosome biosynthesis and translation pathways were up
      regulated. mRNA expression profiles of the cell lines were also compared to those
      of the different types of thyroid cancers. Three datasets originating from
      different microarray platforms and derived from distinct laboratories were used.
      This meta-analysis showed a significant higher correlation between the profiles
      of the thyroid cancer cell lines and ATC, than to differentiated thyroid tumors
      (i.e., PTC or FTC) specifically for DNA replication. This already observed higher
      correlation was obtained here with an increased number of in vivo tumors and
      using different platforms. In summary, this would suggest that some papillary
      thyroid carcinoma or follicular thyroid carcinoma (PTC or FTC) cell lines (i.e.,
      TPC-1) might have partially lost their original DNA synthesis/replication
      regulation mechanisms during their in vitro cell adaptation/evolution.

PMID- 23162535
TI  - Neuropeptide GPCRs in neuroendocrinology: the case of activity-dependent
      neuroprotective protein (ADNP).

PMID- 23162537
TI  - Introduction to special topic-estrogenic control of hypothalamic GnRH neurons.

PMID- 23162536
TI  - Role of calcitonin gene-related peptide in cerebral vasospasm, and as a
      therapeutic approach to subarachnoid hemorrhage.
AB  - Calcitonin gene-related peptide (CGRP) is one of the most potent microvascular
      vasodilators identified to date. Vascular relaxation and vasodilation is mediated
      via activation of the CGRP receptor. This atypical receptor is made up of a G
      protein-coupled receptor called calcitonin receptor-like receptor (CLR), a single
      transmembrane protein called receptor activity-modifying protein (RAMP), and an
      additional protein that is required for Ga(s) coupling, known as receptor
      component protein (RCP). Several mechanisms involved in CGRP-mediated relaxation
      have been identified. These include nitric oxide (NO)-dependent endothelium
      dependent mechanisms or cAMP-mediated endothelium-independent pathways; the
      latter being more common. Subarachnoid hemorrhage (SAH) is associated with
      cerebral vasoconstriction that occurs several days after the hemorrhage and is
      often fatal. The vasospasm occurs in 30-40% of patients and is the major cause of
      death from this condition. The vasoconstriction is associated with a decrease in
      CGRP levels in nerves and an increase in CGRP levels in draining blood,
      suggesting that CGRP is released from nerves to oppose the vasoconstriction. This
      evidence has led to the concept that exogenous CGRP may be beneficial in a
      condition that has proven hard to treat. The present article reviews: (a) the
      pathophysiology of delayed ischemic neurologic deficit after SAH (b) the basics
      of the CGRP receptor structure, signal transduction, and vasodilatation
      mechanisms and (c) the studies that have been conducted so far using CGRP in both
      animals and humans with SAH.

PMID- 23162538
TI  - The VPAC1 receptor: structure and function of a class B GPCR prototype.
AB  - The class B G protein-coupled receptors (GPCRs) represents a small sub-family
      encompassing 15 members, and are very promising targets for the development of
      drugs to treat many diseases such as chronic inflammation, neurodegeneration,
      diabetes, stress, and osteoporosis. The VPAC1 receptor which is an archetype of
      the class B GPCRs binds Vasoactive Intestinal Peptide (VIP), a neuropeptide
      widely distributed in central and peripheral nervous system modulating many
      physiological processes including regulation of exocrine secretions, hormone
      release, foetal development, immune response ... VIP appears to exert beneficial
      effect in neurodegenerative and inflammatory diseases. This article reviews the
      current knowledge regarding the structure and molecular pharmacology of VPAC1
      receptors. Over the past decade, structure-function relationship studies have
      demonstrated that the N-terminal ectodomain (N-ted) of VPAC1 plays a pivotal role
      in VIP recognition. The use of different approaches such as directed mutagenesis,
      photoaffinity labeling, Nuclear Magnetic Resonance (NMR), molecular modeling, and
      molecular dynamic simulation has led to demonstrate that: (1) the central and C
      terminal part of the VIP molecule interacts with the N-ted of VPAC1 receptor
      which is itself structured as a " Sushi " domain; (2) the N-terminal end of the
      VIP molecule interacts with the first transmembrane domain of the receptor where
      three residues (K(143), T(144), and T(147)) play an important role in VPAC1
      interaction with the first histidine residue of VIP.

PMID- 23162539
TI  - Erratum: Acquired antibiotic resistance genes: an overview.

PMID- 23162540
TI  - Identifying reference genes with stable expression from high throughput sequence
      data.
AB  - Genes that are constitutively expressed across multiple environmental stimuli are
      crucial to quantifying differentially expressed genes, particularly when
      employing quantitative reverse transcriptase polymerase chain reaction (RT-qPCR)
      assays. However, the identification of these potential reference genes in non
      model organisms is challenging and is often guided by expression patterns in
      distantly related organisms. Here, transcriptome datasets from the diatom
      Thalassiosira pseudonana grown under replete, phosphorus-limited, iron-limited,
      and phosphorus and iron co-limited nutrient regimes were analyzed through
      literature-based searches for homologous reference genes, k-means clustering, and
      analysis of sequence counts (ASC) to identify putative reference genes. A total
      of 9759 genes were identified and screened for stable expression. Literature
      based searches surveyed 18 generally accepted reference genes, revealing 101
      homologs in T. pseudonana with variable expression and a wide range of mean tags
      per million. k-means analysis parsed the whole transcriptome into 15 clusters.
      The two most stable clusters contained 709 genes, but still had distinct patterns
      in expression. ASC analyses identified 179 genes that were stably expressed
      (posterior probability < 0.1 for 1.25 fold change). Genes known to have a stable
      expression pattern across the test treatments, like actin, were identified in
      this pool of 179 candidate genes. ASC can be employed on data without biological
      replicates and was more robust than the k-means approach in isolating genes with
      stable expression. The intersection of the genes identified through ASC with
      commonly used reference genes from the literature suggests that actin and
      ubiquitin ligase may be useful reference genes for T. pseudonana and potentially
      other diatoms. With the wealth of transcriptome sequence data becoming available,
      ASC can be easily applied to transcriptome datasets from other phytoplankton to
      identify reference genes.

PMID- 23162542
TI  - Clinical pathophysiology of human T-lymphotropic virus-type 1-associated
      myelopathy/tropical spastic paraparesis.
AB  - Human T-lymphotropic virus type 1 (HTLV-1), a human retrovirus, is the causative
      agent of a progressive neurological disease termed HTLV-1-associated
      myelopathy/tropical spastic paraparesis (HAM/TSP). HAM/TSP is a chronic
      inflammatory disease of the central nervous system and is characterized by
      unremitting myelopathic symptoms such as spastic paraparesis, lower limb sensory
      disturbance, and bladder/bowel dysfunction. Approximately 0.25-3.8% of HTLV-1
      infected individuals develop HAM/TSP, which is more common in women than in men.
      Since the discovery of HAM/TSP, significant advances have been made with respect
      to elucidating the virological, molecular, and immunopathological mechanisms
      underlying this disease. These findings suggest that spinal cord invasion by HTLV
      1-infected T cells triggers a strong virus-specific immune response and increases
      proinflammatory cytokine and chemokine production, leading to chronic lymphocytic
      inflammation and tissue damage in spinal cord lesions. However, little progress
      has been made in the development of an optimal treatment for HAM/TSP, more
      specifically in the identification of biomarkers for predicting disease
      progression and of molecular targets for novel therapeutic strategies targeting
      the underlying pathological mechanisms. This review summarizes current clinical
      and pathophysiological knowledge on HAM/TSP and discusses future focus areas for
      research on this disease.

PMID- 23162543
TI  - Polyextremotolerant black fungi: oligotrophism, adaptive potential, and a link to
      lichen symbioses.
AB  - Black meristematic fungi can survive high doses of radiation and are resistant to
      desiccation. These adaptations help them to colonize harsh oligotrophic habitats,
      e.g., on the surface and subsurface of rocks. One of their most characteristic
      stress-resistance mechanisms is the accumulation of melanin in the cell walls.
      This, production of other protective molecules and a plastic morphology further
      contribute to ecological flexibility of black fungi. Increased growth rates of
      some species after exposure to ionizing radiation even suggest yet unknown
      mechanisms of energy production. Other unusual metabolic strategies may include
      harvesting UV or visible light or gaining energy by forming facultative lichen
      like associations with algae or cyanobacteria. The latter is not entirely
      surprising, since certain black fungal lineages are phylogenetically related to
      clades of lichen-forming fungi. Similar to black fungi, lichen-forming fungi are
      adapted to growth on exposed surfaces with low availability of nutrients. They
      also efficiently use protective molecules to tolerate frequent periods of extreme
      stress. Traits shared by both groups of fungi may have been important in
      facilitating the evolution and radiation of lichen-symbioses.

PMID- 23162541
TI  - Epidemiological Aspects and World Distribution of HTLV-1 Infection.
AB  - The human T-cell leukemia virus type 1 (HTLV-1), identified as the first human
      oncogenic retrovirus 30 years ago, is not an ubiquitous virus. HTLV-1 is present
      throughout the world, with clusters of high endemicity located often nearby areas
      where the virus is nearly absent. The main HTLV-1 highly endemic regions are the
      Southwestern part of Japan, sub-Saharan Africa and South America, the Caribbean
      area, and foci in Middle East and Australo-Melanesia. The origin of this puzzling
      geographical or rather ethnic repartition is probably linked to a founder effect
      in some groups with the persistence of a high viral transmission rate. Despite
      different socio-economic and cultural environments, the HTLV-1 prevalence
      increases gradually with age, especially among women in all highly endemic areas.
      The three modes of HTLV-1 transmission are mother to child, sexual transmission,
      and transmission with contaminated blood products. Twenty years ago, de The and
      Bomford estimated the total number of HTLV-1 carriers to be 10-20 millions
      people. At that time, large regions had not been investigated, few population
      based studies were available and the assays used for HTLV-1 serology were not
      enough specific. Despite the fact that there is still a lot of data lacking in
      large areas of the world and that most of the HTLV-1 studies concern only blood
      donors, pregnant women, or different selected patients or high-risk groups, we
      shall try based on the most recent data, to revisit the world distribution and
      the estimates of the number of HTLV-1 infected persons. Our best estimates range
      from 5-10 millions HTLV-1 infected individuals. However, these results were based
      on only approximately 1.5 billion of individuals originating from known HTLV-1
      endemic areas with reliable available epidemiological data. Correct estimates in
      other highly populated regions, such as China, India, the Maghreb, and East
      Africa, is currently not possible, thus, the current number of HTLV-1 carriers is
      very probably much higher.

PMID- 23162544
TI  - Toward system-level understanding of baculovirus-host cell interactions: from
      molecular fundamental studies to large-scale proteomics approaches.
AB  - Baculoviruses are insect viruses extensively exploited as eukaryotic protein
      expression vectors. Molecular biology studies have provided exciting discoveries
      on virus-host interactions, but the application of omic high-throughput
      techniques on the baculovirus-insect cell system has been hampered by the lack of
      host genome sequencing. While a broader, systems-level analysis of biological
      responses to infection is urgently needed, recent advances on proteomic studies
      have yielded new insights on the impact of infection on the host cell. These
      works are reviewed and critically assessed in the light of current biological
      knowledge of the molecular biology of baculoviruses and insect cells.

PMID- 23162545
TI  - Current approaches on viral infection: proteomics and functional validations.
AB  - Viruses could manipulate cellular machinery to ensure their continuous survival
      and thus become parasites of living organisms. Delineation of sophisticated host
      responses upon virus infection is a challenging task. It lies in identifying the
      repertoire of host factors actively involved in the viral infectious cycle and
      characterizing host responses qualitatively and quantitatively during viral
      pathogenesis. Mass spectrometry based proteomics could be used to efficiently
      study pathogen-host interactions and virus-hijacked cellular signaling pathways.
      Moreover, direct host and viral responses upon infection could be further
      investigated by activity-based functional validation studies. These approaches
      involve drug inhibition of secretory pathway, immunofluorescence staining,
      dominant negative mutant of protein target, real-time PCR, small interfering
      siRNA-mediated knockdown, and molecular cloning studies. In this way, functional
      validation could gain novel insights into the high-content proteomic dataset in
      an unbiased and comprehensive way.

PMID- 23162546
TI  - Generation and Characterization of UL21-Null Herpes Simplex Virus Type 1.
AB  - UL21 of herpes simplex virus type 1 (HSV-1) is an accessory gene that encodes a
      component of the tegument. Homologs of this protein have been identified in the
      alpha, beta, and gamma herpesvirus subfamilies, although their functions are
      unclear. To clarify the functions of UL21, we generated a UL21-null HSV-1 mutant.
      Growth analysis showed that the synthesis of infectious UL21-null HSV-1 in glial
      cells was delayed and that the overall yield was low. The plaque sizes of the
      UL21-null mutant were smaller than those of wild-type HSV-1. We identified
      several candidate UL21-interacting proteins, including intermediate filaments, by
      yeast two-hybrid screening. The distribution of glial fibrillary acidic protein
      (GFAP), which is the main component of intermediate filaments, was altered in
      UL21-null mutant-infected glial cells compared to wild-type virus-infected cells.
      These results will help clarify the function of UL21 and broaden our
      understanding of the life cycle of HSV.

PMID- 23162547
TI  - The molecular mechanisms of chronic inflammation development.

PMID- 23162548
TI  - NOD1 and NOD2 Signaling in Infection and Inflammation.
AB  - Sensing intracellular pathogens is a process mediated by innate immune cells that
      is crucial for the induction of inflammatory processes and effective adaptive
      immune responses against pathogenic microbes. NOD-like receptors (NLRs) comprise
      a family of intracellular pattern recognition receptors that are important for
      the recognition of damage and microbial-associated molecular patterns. NOD1 and
      NOD2 are specialized NLRs that participate in the recognition of a subset of
      pathogenic microorganisms that are able to invade and multiply intracellularly.
      Once activated, these molecules trigger intracellular signaling pathways that
      lead to the activation of transcriptional responses culminating in the expression
      of a subset of inflammatory genes. In this review, we will focus on the role of
      NOD1 and NOD2 in the recognition and response to intracellular pathogens,
      including Gram-positive and Gram-negative bacteria, and on their ability to
      signal in response to non-peptidoglycan-containing pathogens, such as viruses and
      protozoan parasites.

PMID- 23162549
TI  - Novel murine dendritic cell lines: a powerful auxiliary tool for dendritic cell
      research.
AB  - Research in vitro facilitates discovery, screening, and pilot experiments, often
      preceding research in vivo. Several technical difficulties render Dendritic Cell
      (DC) research particularly challenging, including the low frequency of DC in
      vivo, thorough isolation requirements, and the vulnerability of DC ex vivo.
      Critically, there is not as yet a widely accepted human or murine DC line and in
      vitro systems of DC research are limited. In this study, we report the generation
      of new murine DC lines, named MutuDC, originating from cultures of splenic
      CD8alpha conventional DC (cDC) tumors. By direct comparison to normal WT splenic
      cDC subsets, we describe the phenotypic and functional features of the MutuDC
      lines and show that they have retained all the major features of their natural
      counterpart in vivo, the splenic CD8alpha cDC. These features include expression
      of surface markers Clec9A, DEC205, and CD24, positive response to TLR3 and TLR9
      but not TLR7 stimuli, secretion of cytokines, and chemokines upon activation, as
      well as cross-presentation capacity. In addition to the close resemblance to
      normal splenic CD8alpha cDC, a major advantage is the ease of derivation and
      maintenance of the MutuDC lines, using standard culture medium and conditions,
      importantly without adding supplementary growth factors or maturation-inducing
      stimuli to the medium. Furthermore, genetically modified MutuDC lines have been
      successfully obtained either by lentiviral transduction or by culture of DC
      tumors originating from genetically modified mice. In view of the current lack of
      stable and functional DC lines, these novel murine DC lines have the potential to
      serve as an important auxiliary tool for DC research.

PMID- 23162550
TI  - Targeting 4-1BB (CD137) to enhance CD8 T cell responses with poxviruses and viral
      antigens.
AB  - Attenuated vaccinia virus (VACV) vectors are considered prime vaccine candidates
      for use in immunotherapy of infectious disease. In spite of this, recent data
      show that the level of attenuation may hamper the efficient generation of
      protective CD8 T cells. This suggests that additional adjuvant-like activities
      may need to be combined with attenuated VACV for optimal vaccination. Stimulatory
      reagents to the TNFR family molecule 4-1BB (CD137) may represent such an adjuvant
      for vaccination. Previous murine studies have found that 4-1BB can participate in
      optimal priming of effector and memory CD8 T cells in response to several virus
      infections, and concordantly direct stimulation of 4-1BB with agonist reagents
      effectively boosts the CD8 T cell response against those viruses. In contrast, we
      recently reported that 4-1BB plays no role in the response to a virulent strain
      of VACV, questioning whether agonists of 4-1BB will be useful adjuvants for
      vaccination with VACV vectors. Here we show that agonist anti-4-1BB strongly
      enhanced the primary viral-specific effector CD8 T cell response during infection
      with live virulent VACV and attenuated VACV, and during immunization with VACV
      peptides given in IFA. However, accumulation of memory CD8 T cells was enhanced
      only following infection with virulent VACV or with peptide vaccination, but not
      with attenuated VACV, correlating in part with more transient expression of 4-1BB
      on CD8 T cells with attenuated virus. Our data therefore suggest that 4-1BB may
      be a promising candidate for targeting as an adjuvant for short-term enhancement
      of CD8 T cell responses with VACV vaccine strategies, but additional receptors
      may need to be engaged with 4-1BB to allow long-term CD8 T cell immunity with
      attenuated VACV vectors.

PMID- 23162551
TI  - Abundant neutrophil extracellular traps in thrombus of patient with microscopic
      polyangiitis.
AB  - This is a case study of a patient diagnosed with microscopic polyangiitis (MPA)
      and complicated with deep vein thrombosis (DVT), who died of respiratory failure
      despite treatment. Autopsy revealed severe crescentic glomerulonephritis and
      massive alveolar hemorrhage. The thrombus contained abundant neutrophils.
      Although it is reported that patients with ANCA-associated vasculitis (AAV) have
      an increased risk of DVT, it remains elusive why they are prone to thrombosis. A
      recent study has demonstrated the presence of neutrophil extracellular traps
      (NETs), a newly recognized mode of neutrophil cell-death, in glomerular crescents
      of MPA patients. Interestingly, NETs were identified in the thrombus as well as
      in the glomerular crescents in the present case. When compared to other thrombi
      unrelated to MPA, the amount of NETs was significantly greater in the MPA
      patient. On the other hand, NETs are critically involved in thrombogenesis
      because histones within NETs can bind platelets and blood coagulants. Although
      this is important in regard to containment of microbes within NETs, excessive
      NETs could cause thrombosis. The collective findings suggest the possibility that
      thrombosis could be critically associated with MPA via NETs, and that NETs could
      be a therapeutic target in MPA patients.

PMID- 23162552
TI  - Sculpting humoral immunity through dengue vaccination to enhance protective
      immunity.
AB  - Dengue viruses (DENV) are the most important mosquito transmitted viral pathogens
      infecting humans. DENV infection produces a spectrum of disease, most commonly
      causing a self-limiting flu-like illness known as dengue fever; yet with
      increased frequency, manifesting as life-threatening dengue hemorrhagic fever
      (DHF). Waning cross-protective immunity from any of the four dengue serotypes may
      enhance subsequent infection with another heterologous serotype to increase the
      probability of DHF. Decades of effort to develop dengue vaccines are reaching the
      finishing line with multiple candidates in clinical trials. Nevertheless,
      concerns remain that imbalanced immunity, due to the prolonged prime-boost
      schedules currently used in clinical trials, could leave some vaccinees
      temporarily unprotected or with increased susceptibility to enhanced disease.
      Here we develop a DENV serotype 1 (DENV-1) DNA vaccine with the immunodominant
      cross-reactive B cell epitopes associated with immune enhancement removed. We
      compare wild-type (WT) with this cross-reactivity reduced (CRR) vaccine and
      demonstrate that both vaccines are equally protective against lethal homologous
      DENV-1 challenge. Under conditions mimicking natural exposure prior to acquiring
      protective immunity, WT vaccinated mice enhanced a normally sub-lethal
      heterologous DENV-2 infection resulting in DHF-like disease and 95% mortality in
      AG129 mice. However, CRR vaccinated mice exhibited redirected serotype-specific
      and protective immunity, and significantly reduced morbidity and mortality not
      differing from naive mice. Thus, we demonstrate in an in vivo DENV disease model,
      that non-protective vaccine-induced immunity can prime vaccinees for enhanced DHF
      like disease and that CRR DNA immunization significantly reduces this potential
      vaccine safety concern. The sculpting of immune memory by the modified vaccine
      and resulting redirection of humoral immunity provide insight into DENV vaccine
      induced immune responses.

PMID- 23162554
TI  - New perspectives on the ligands and function of the killer cell immunoglobulin
      like receptor KIR3DL2 in health and disease.
AB  - KIR3DL2/CD158k/p140 is a three domain killer cell immunoglobulin-like receptor
      incorporating cytoplasmic immunoreceptor tyrosine inhibitory motifs, expressed as
      a disulphide-bonded dimer. KIR3DL2 is a framework gene within the KIR locus and
      is highly polymorphic, with 62 allelic variants possibly coding for protein
      reported. KIR3DL2 binds to HLA-A3 and -A11 in a peptide-dependent fashion and to
      B27 free heavy chain forms. In addition, KIR3DL2 can also function as an innate
      immune receptor for delivery of CpG DNA to TLR9 in NK cells. The increased levels
      of expression of KIR3DL2 compared with other KIR expressed by T cell subsets in
      healthy individuals suggest it may function as a default KIR receptor. KIR3DL2
      expressing natural killer (NK) cells and IL17 secreting CD4 T cells have been
      implicated in the pathogenesis of ankylosing spondylitis. Moreover, KIR3DL2
      expression delineates circulating and cutaneous lymphoma T cells in Sezary's
      syndrome. Here we discuss how the unique molecular attributes of KIR3DL2 impact
      on its function on NK and T cells and how this may relate to its role in disease.

PMID- 23162553
TI  - Human NK cell lytic granules and regulation of their exocytosis.
AB  - Natural killer (NK) cells form a subset of lymphocytes that play a key role in
      immuno-surveillance and host defense against cancer and viral infections. They
      recognize stressed cells through a variety of germline-encoded activating cell
      surface receptors and utilize their cytotoxic ability to eliminate abnormal
      cells. Killing of target cells is a complex, multi-stage process that concludes
      in the directed secretion of lytic granules, containing perforin and granzymes,
      at the immunological synapse. Upon delivery to a target cell, perforin mediates
      generation of pores in membranes of target cells, allowing granzymes to access
      target cell cytoplasm and induce apoptosis. Therefore, lytic granules of NK cells
      are indispensable for normal NK cell cytolytic function. Indeed, defects in lytic
      granule secretion lead or are related to serious and often fatal diseases, such
      as familial hemophagocytic lymphohistiocytosis (FHL) type 2-5 or Griscelli
      syndrome type 2. A number of reports highlight the role of several proteins
      involved in lytic granule release and NK cell-mediated killing of tumor cells.
      This review focuses on lytic granules of human NK cells and the advancements in
      understanding the mechanisms controlling their exocytosis.

PMID- 23162555
TI  - Local immunity by tissue-resident CD8(+) memory T cells.
AB  - Microbial infection primes a CD8(+) cytotoxic T cell response that gives rise to
      a long-lived population of circulating memory cells able to provide protection
      against systemic reinfection. Despite this, effective CD8(+) T cell surveillance
      of barrier tissues such as skin and mucosa typically wanes with time, resulting
      in limited T cell-mediated protection in these peripheral tissues. However,
      recent evidence suggests that a specialized subset of CD103(+) memory T cells can
      permanently lodge and persist in peripheral tissues, and that these cells can
      compensate for the loss of peripheral immune surveillance by circulating memory T
      cells. Here, we review evolving concepts regarding the generation and long-term
      persistence of these tissue-resident memory T cells (T(RM)) in epithelial and
      neuronal tissues. We further discuss the role of T(RM) cells in local infection
      control and their contribution to localized immune phenomena, in both mice and
      humans.

PMID- 23162557
TI  - Application of tissue engineering to the immune system: development of artificial
      lymph nodes.
AB  - The goal of tissue engineering and regenerative medicine is to develop synthetic
      versions of human organs for transplantation, in vitro toxicology testing and to
      understand basic mechanisms of organ function. A variety of different approaches
      have been utilized to replicate the microenvironments found in lymph nodes
      including the use of a variety of different bio-materials, culture systems, and
      the application of different cell types to replicate stromal networks found in
      vivo. Although no system engineered so far can fully replicate lymph node
      function, progress has been made in the development of microenvironments that can
      promote the initiation of protective immune responses. In this review we will
      explore the different approaches utilized to recreate lymph node
      microenvironments and the technical challenges required to recreate a fully
      functional immune system in vitro.

PMID- 23162558
TI  - Sequencing of chloroplast genome using whole cellular DNA and solexa sequencing
      technology.
AB  - Sequencing of the chloroplast (cp) genome using traditional sequencing methods
      has been difficult because of its size (>120 kb) and the complicated procedures
      required to prepare templates. To explore the feasibility of sequencing the cp
      genome using DNA extracted from whole cells and Solexa sequencing technology, we
      sequenced whole cellular DNA isolated from leaves of three Brassicarapa
      accessions with one lane per accession. In total, 246, 362, and 361 Mb sequence
      data were generated for the three accessions Chiifu-401-42, Z16, and FT,
      respectively. Micro-reads were assembled by reference-guided assembly using the
      cpDNA sequences of B. rapa, Arabidopsis thaliana, and Nicotiana tabacum. We
      achieved coverage of more than 99.96% of the cp genome in the three tested
      accessions using the B. rapa sequence as the reference. When A. thaliana or N.
      tabacum sequences were used as references, 99.7-99.8 or 95.5-99.7% of the B. rapa
      cp genome was covered, respectively. These results demonstrated that sequencing
      of whole cellular DNA isolated from young leaves using the Illumina Genome
      Analyzer is an efficient method for high-throughput sequencing of cp genome.

PMID- 23162556
TI  - Natural and man-made V-gene repertoires for antibody discovery.
AB  - Antibodies are the fastest-growing segment of the biologics market. The success
      of antibody-based drugs resides in their exquisite specificity, high potency,
      stability, solubility, safety, and relatively inexpensive manufacturing process
      in comparison with other biologics. We outline here the structural studies and
      fundamental principles that define how antibodies interact with diverse targets.
      We also describe the antibody repertoires and affinity maturation mechanisms of
      humans, mice, and chickens, plus the use of novel single-domain antibodies in
      camelids and sharks. These species all utilize diverse evolutionary solutions to
      generate specific and high affinity antibodies and illustrate the plasticity of
      natural antibody repertoires. In addition, we discuss the multiple variations of
      man-made antibody repertoires designed and validated in the last two decades,
      which have served as tools to explore how the size, diversity, and composition of
      a repertoire impact the antibody discovery process.

PMID- 23162559
TI  - The membrane-tethered transcription factor ANAC089 serves as redox-dependent
      suppressor of stromal ascorbate peroxidase gene expression.
AB  - The stromal ascorbate peroxidase (sAPX) functions as central element of the
      chloroplast antioxidant defense system. Its expression is under retrograde
      control of chloroplast signals including redox- and reactive oxygen species
      linked cues. The sAPX promoter of Arabidopsis thaliana was dissected in transient
      reporter assays using mesophyll protoplasts. The study revealed regulatory
      elements up to -1868 upstream of the start codon. By yeast-one-hybrid screening,
      the transcription factor ANAC089 was identified to bind to the promoter fragment
      2 (-1262 to -1646 bp upstream of translational initiation). Upon mutation of the
      cis-acting element CACG, binding of ANAC089 was abolished. Expression of a fused
      fluorescent protein version and comparison with known endomembrane markers
      localized ANAC089 to the trans-Golgi network and the ER. The transcription factor
      was released upon treatment with reducing agents and targeted to the nucleus.
      Transactivation assays using wild type and mutated versions of the promoter
      showed a partial suppression of reporter expression. The data indicate that
      ANAC089 functions in a negative retrograde loop, lowering sAPX expression if the
      cell encounters a highly reducing condition. This conclusion was supported by
      reciprocal transcript accumulation of ANAC089 and sAPX during acclimation to low,
      normal, and high light conditions.

PMID- 23162560
TI  - Co-expression and co-responses: within and beyond transcription.
AB  - Whole genome sequencing, the relative ease of transcript profiling by the use of
      microarrays and latterly RNA sequencing approaches have facilitated the capture
      of vast amounts of transcript data. However, despite the enormous progress made
      in gene annotation a substantial proportion of genes remain to be annotated at
      the functional level. Considerable progress has, however, been made by searching
      for transcriptional coordination between genes of known function and non
      annotated genes on the premise that such co-expressed genes tend to be
      functionally related. Here we review progress made following this approach as
      well as its expansion to include phenotypic information from other levels of
      cellular organization such as proteomic and metabolomic data as well as
      physiological and developmental phenotypes.

PMID- 23162561
TI  - Compromise of multiple time-resolved transcriptomics experiments identifies
      tightly regulated functions.
AB  - With the advent of high-throughput technologies for data acquisition from
      different components (i.e., genes, proteins, and metabolites) of a given
      biological system, generation of hypotheses, and biological interpretations based
      on multivariate data sets become increasingly important. These technologies allow
      for simultaneous gathering of data from the same biological components under
      different perturbations, including genotypic variation and/or changes in
      conditions, resulting in so-called multiple data tables. Moreover, these data
      tables are obtained over a well-chosen time domain to capture the dynamics of the
      response of the biological system to the perturbation. The computational problem
      we address in this study is twofold: (1) derive a single data table, referred to
      as a compromise, which captures information common to the investigated set of
      multiple tables and (2) identify biological components which contribute most to
      the determined compromise. Here we argue that recent extensions to principle
      component analysis called STATIS and dual-STATIS can be used to determine the
      compromise on which classical techniques for data analysis, such as clustering
      and term over-enrichment, can be subsequently applied. In addition, we illustrate
      that STATIS and dual-STATIS facilitate interpretations of a publically available
      transcriptomics data set capturing the time-resolved response of Arabidopsis
      thaliana to changing light and/or temperature conditions. We demonstrate that
      STATIS and dual-STATIS can be used not only to identify the components of a
      biological system whose behavior is similarly affected due to the perturbation
      (e.g., in time or condition), but also to specify the extent to which each
      dimension of the data tables reflect the perturbation. These findings ultimately
      provide insights in the components and pathways which could be under tight
      control in plant systems.

PMID- 23162562
TI  - Evolutionary Adaptations of Plant AGC Kinases: From Light Signaling to Cell
      Polarity Regulation.
AB  - Signaling and trafficking over membranes involves a plethora of transmembrane
      proteins that control the flow of compounds or relay specific signaling events.
      Next to external cues, internal stimuli can modify the activity or abundance of
      these proteins at the plasma membrane (PM). One such regulatory mechanism is
      protein phosphorylation by membrane-associated kinases, several of which are AGC
      kinases. The AGC kinase family is one of seven kinase families that are conserved
      in all eukaryotic genomes. In plants evolutionary adaptations introduced specific
      structural changes within the AGC kinases that most likely allow modulation of
      kinase activity by external stimuli (e.g., light). Starting from the well-defined
      structural basis common to all AGC kinases we review the current knowledge on the
      structure-function relationship in plant AGC kinases. Nine of the 39 Arabidopsis
      AGC kinases have now been shown to be involved in the regulation of auxin
      transport. In particular, AGC kinase-mediated phosphorylation of the auxin
      transporters ABCB1 and ABCB19 has been shown to regulate their activity, while
      auxin transporters of the PIN family are located to different positions at the PM
      depending on their phosphorylation status, which is a result of counteracting AGC
      kinase and PP6 phosphatase activities. We therefore focus on regulation of AGC
      kinase activity in this context. Identified structural adaptations of the
      involved AGC kinases may provide new insight into AGC kinase functionality and
      demonstrate their position as central hubs in the cellular network controlling
      plant development and growth.

PMID- 23162563
TI  - The putative K(+) channel subunit AtKCO3 forms stable dimers in Arabidopsis.
AB  - The permeation pore of K(+) channels is formed by four copies of the pore domain.
      AtKCO3 is the only putative voltage-independent K(+) channel subunit of
      Arabidopsis thaliana with a single pore domain. KCO3-like proteins recently
      emerged in evolution and, to date, have been found only in the genus Arabidopsis
      (A. thaliana and A. lyrata). We show that the absence of KCO3 does not cause
      marked changes in growth under various conditions. Only under osmotic stress we
      observed reduced root growth of the kco3-1 null-allele line. This phenotype was
      complemented by expressing a KCO3 mutant with an inactive pore, indicating that
      the function of KCO3 under osmotic stress does not depend on its direct ability
      to transport ions. Constitutively overexpressed AtKCO3 or AtKCO3::GFP are
      efficiently sorted to the tonoplast indicating that the protein is approved by
      the endoplasmic reticulum quality control. However, vacuoles isolated from
      transgenic plants do not have significant alterations in current density.
      Consistently, both AtKCO3 and AtKCO3::GFP are detected as homodimers upon
      velocity gradient centrifugation, an assembly state that would not allow for
      activity. We conclude that if AtKCO3 ever functions as a K(+) channel, active
      tetramers are held by particularly weak interactions, are formed only in unknown
      specific conditions and may require partner proteins.

PMID- 23162565
TI  - Plant mitochondrial retrograde signaling: post-translational modifications enter
      the stage.
AB  - Beside their central function in respiration plant mitochondria play important
      roles in diverse processes such as redox homeostasis, provision of precursor
      molecules for essential biosynthetic pathways, and programmed cell death. These
      different functions require the organelle to communicate with the rest of the
      cell by perceiving, transducing, and emitting signals. As the vast majority of
      mitochondrial proteins are encoded in the nuclear genome, changes in
      mitochondrial status must be fed back to the nucleus to coordinate gene
      expression accordingly, a process termed retrograde signaling. However, the
      nature of these signaling pathways in plants and their underlying signaling
      molecules - or indirect metabolite or redox signals - are not completely
      resolved. We explore the potential of different post-translational modifications
      (PTMs) to contribute to mitochondrial retrograde signaling. Remarkably, the
      substrates used for modifying proteins in many major PTMs are either central
      metabolites or redox-active compounds, as for example ATP, acetyl-CoA, NAD(+),
      and glutathione. This suggests that the metabolic status of organelles and of the
      cell in general could be indirectly gaged by the enzymes catalyzing the various
      PTMs. We examine the evidence supporting this hypothesis with regard to three
      major PTMs, namely phosphorylation, lysine acetylation, and glutathionylation and
      assess their potential to regulate not only organellar processes by modifying
      metabolic enzymes but also to influence nuclear gene expression.

PMID- 23162564
TI  - Visual analysis of transcriptome data in the context of anatomical structures and
      biological networks.
AB  - The complexity and temporal as well as spatial resolution of transcriptome
      datasets is constantly increasing due to extensive technological developments.
      Here we present methods for advanced visualization and intuitive exploration of
      transcriptomics data as necessary prerequisites in order to facilitate the gain
      of biological knowledge. Color-coding of structural images based on the
      expression level enables a fast visual data analysis in the background of the
      examined biological system. The network-based exploration of these visualizations
      allows for comparative analysis of genes with specific transcript patterns and
      supports the extraction of functional relationships even from large datasets. In
      order to illustrate the presented methods, the tool HIVE was applied for
      visualization and exploration of database-retrieved expression data for master
      regulators of Arabidopsis thaliana flower and seed development in the context of
      corresponding tissue-specific regulatory networks.

PMID- 23162566
TI  - Morphine and microRNA Activity: Is There a Relation with Addiction?
AB  - When we talk about drug addiction, we are really dealing with an extremely
      complex system in which there still remain many unknowns and where many empty
      spaces or missing links are still present. Recent studies have identified changes
      in the expression profiles of several specific miRNAs which affect the
      interactions between these molecules and their targets in various illnesses,
      including addiction, and which may serve as valuable targets for more efficient
      therapies. In this review, we summarize results which clearly demonstrate that
      several morphine-related miRNAs have roles in the mechanisms that define
      addiction. In this regard, morphine has been shown to have an important role in
      the regulation of different miRNAs, such as miR-let-7 [which works as a mediator
      of the movement of the mu opioid receptor (MOR) mRNA into P-bodies, leading to
      translational repression], miR-23b (involved in linking MOR expression and
      morphine treatment at the post-transcriptional level), and miR-190 (a key post
      transcriptional repressor of neurogenic differentiation, NeuroD). Fentanyl
      increases NeuroD levels by reducing the amount of miR-190, but morphine does not
      affect the levels of NeuroD. We also discuss the relationship between morphine,
      miRNAs, and the immune system, based on the discovery that morphine treatment of
      monocytes led to a decrease in several anti-HIV miRNAs (mir-28, 125b, 150, and
      382). This review is centered on miR-133b and its possible involvement in
      addiction through the effects of morphine. We establish the importance of miR
      133b as a regulatory factor by summarizing its activity in different pathological
      processes, especially cancer. Using the zebrafish as a research model, we discuss
      the relationship between mir-133b, the dopaminergic system, and morphine,
      considering: (1) that morphine modulates the expression of miR-133b and of its
      target transcript Pitx3, (2) the role of the zebrafish mu opioid receptor (zfMOR)
      in morphine-induced regulation of miR-133b, which depends on ERK1/2, (3) that
      morphine regulates miR-133b in hippocampal neurons, and (4) the role of delta
      opioid receptors in morphine-induced regulation of miR-133b. We conclude that the
      control of miR-133b levels may be a mechanism for the development of addiction to
      morphine, or other drugs of abuse that increase dopaminergic levels in the
      extracellular space. These results show that miR-133b is a possible new target
      for the design of new treatments against addictive disorders.

PMID- 23162567
TI  - DNA Methylation of Tumor Suppressive miRNAs in Non-Hodgkin's Lymphomas.
AB  - DNA methylation is an epigenetic alteration leading to heritable phenotypic
      changes of cells with functional consequences. It is important in early embryonic
      development, stem cell differentiation, and tissue-specific gene expression. In
      normal cells, promoter-associated CpG islands (CGI) are generally unmethylated
      except in X-chromosome inactivation or genomic imprinting. In cancer, tumor cells
      are characterized by global hypomethylation but locus-specific hypermethylation
      of promoter-associated CGI, resulting in gene silencing. MicroRNAs (miRNAs) are
      short, non-coding RNA sequences of 18-25 nucleotides, which can repress the
      translational of multiple protein-coding mRNAs by sequence-specific binding to
      the 3'untranslated region. Depending on the genes targeted, miRNA can be tumor
      suppressive if an oncogene is repressed, or it can be oncogenic when a tumor
      suppressive gene is repressed. Recently, aberrant methylation of tumor
      suppressive miRNAs has been reported in different types of cancers including
      lymphomas. Herein, we review the recent literature of methylation of tumor
      suppressive miRNAs in different histopathologic subtypes of lymphomas, and
      discuss its potential diagnostic, prognostic, and therapeutic significance.

PMID- 23162568
TI  - MDMA, methamphetamine, and CYP2D6 pharmacogenetics: what is clinically relevant?
AB  - In vitro human studies show that the metabolism of most amphetamine-like
      psychostimulants is regulated by the polymorphic cytochrome P450 isozyme CYP2D6.
      Two compounds, methamphetamine and 3,4-methylenedioxymethamphetamine (MDMA), were
      selected as archetypes to discuss the translation and clinical significance of in
      vitro to in vivo findings. Both compounds were chosen based on their differential
      interaction with CYP2D6 and their high abuse prevalence in society.
      Methamphetamine behaves as both a weak substrate and competitive inhibitor of
      CYP2D6, while MDMA acts as a high affinity substrate and potent mechanism-based
      inhibitor (MBI) of the enzyme. The MBI behavior of MDMA on CYP2D6 implies that
      subjects, irrespective of their genotype/phenotype, are phenocopied to the poor
      metabolizer (PM) phenotype. The fraction of metabolic clearance regulated by
      CYP2D6 for both drugs is substantially lower than expected from in vitro studies.
      Other isoenzymes of cytochrome P450 and a relevant contribution of renal
      excretion play a part in their clearance. These facts tune down the potential
      contribution of CYP2D6 polymorphism in the clinical outcomes of both substances.
      Globally, the clinical relevance of CYP2D6 polymorphism is lower than that
      predicted by in vitro studies.

PMID- 23162570
TI  - Does Lin28 Antagonize miRNA-Mediated Repression by Displacing miRISC from Target
      mRNAs?
AB  - Lin28 is a developmentally regulated RNA-binding protein that plays important
      roles in diverse physiological and pathological processes including oncogenesis
      and brain synaptic function. These pleiotropic roles of Lin28 are mechanistically
      linked both to its ability to directly stimulate translation of genes involved
      primarily in cell growth and metabolism and to its ability to block biogenesis of
      a subset of miRNAs including the let-7 family of miRNAs. In the case of direct
      stimulation of gene expression, Lin28 binds to targeted mRNAs through recognition
      of Lin28-responsive elements (LREs) within mRNAs and recruits RNA helicase A
      (RHA) to promote translation. RHA belongs to the DEAD-box protein family of RNA
      helicases, which generally catalyze ATP-dependent unwinding of RNA duplexes or
      remodeling of ribonucleoprotein complexes (RNPs). Since any given mRNA can
      potentially be inhibited by miRNAs bearing complementary sequences, we
      hypothesize that binding of Lin28 to LREs not only nucleates the binding of
      multiple Lin28 molecules to the same mRNA, but also leads to remodeling of RNPs
      through recruitment of RHA and causes release of inhibitory miRNA-induced
      silencing complexes bound to the mRNA. This mode of action may contribute to
      Lin28-mediated stimulation of translation in both tumor and neuronal cells.

PMID- 23162569
TI  - Age-by-disease biological interactions: implications for late-life depression.
AB  - Onset of depressive symptoms after the age of 65, or late-life depression (LLD),
      is common and poses a significant burden on affected individuals, caretakers, and
      society. Evidence suggests a unique biological basis for LLD, but current
      hypotheses do not account for its pathophysiological complexity. Here we propose
      a novel etiological framework for LLD, the age-by-disease biological interaction
      hypothesis, based on the observations that the subset of genes that undergoes
      lifelong progressive changes in expression is restricted to a specific set of
      biological processes, and that a disproportionate number of these age-dependent
      genes have been previously and similarly implicated in neurodegenerative and
      neuropsychiatric disorders, including depression. The age-by-disease biological
      interaction hypothesis posits that age-dependent biological processes (i) are
      "pushed" in LLD-promoting directions by changes in gene expression naturally
      occurring during brain aging, which (ii) directly contribute to
      pathophysiological mechanisms of LLD, and (iii) that individual variability in
      rates of age-dependent changes determines risk or resiliency to develop age
      related disorders, including LLD. We review observations supporting this
      hypothesis, including consistent and specific age-dependent changes in brain gene
      expression and their overlap with neuropsychiatric and neurodegenerative disease
      pathways. We then review preliminary reports supporting the genetic component of
      this hypothesis. Other potential biological mediators of age-dependent gene
      changes are proposed. We speculate that studies examining the relative
      contribution of these mechanisms to age-dependent changes and related disease
      mechanisms will not only provide critical information on the biology of normal
      aging of the human brain, but will inform our understanding of age-dependent
      diseases, in time fostering the development of new interventions for prevention
      and treatment of age-dependent diseases, including LLD.

PMID- 23162571
TI  - Using blood informative transcripts in geographical genomics: impact of lifestyle
      on gene expression in fijians.
AB  - In previous geographical genomics studies of the impact of lifestyle on gene
      expression inferred from microarray analysis of peripheral blood samples, we
      described the complex influences of culture, ethnicity, and gender in Morocco,
      and of pregnancy in Brisbane. Here we describe the use of nanofluidic Fluidigm
      quantitative RT-PCR arrays targeted at a set of 96 transcripts that are broadly
      informative of the major axes of immune gene expression, to explore the
      population structure of transcription in Fiji. As in Morocco, major differences
      are seen between the peripheral blood transcriptomes of rural villagers and
      residents of the capital city, Suva. The effect is much greater in Indian
      villages than in Melanesian highlanders and appears to be similar with respect to
      the nature of at least two axes of variation. Gender differences are much smaller
      than ethnicity or lifestyle effects. Body mass index is shown to associate with
      one of the axes as it does in Atlanta and Brisbane, establishing a link between
      the epidemiological transition of human metabolic disease, and gene expression
      profiles.

PMID- 23162573
TI  - Genetic variations in drug-induced liver injury (DILI): resolving the puzzle.

PMID- 23162572
TI  - The role of CTCF binding sites in the 3' immunoglobulin heavy chain regulatory
      region.
AB  - The immunoglobulin heavy chain locus undergoes a series of DNA rearrangements and
      modifications to achieve the construction and expression of individual antibody
      heavy chain genes in B cells. These events affect variable regions, through VDJ
      joining and subsequent somatic hypermutation, and constant regions through class
      switch recombination (CSR). Levels of IgH expression are also regulated during B
      cell development, resulting in high levels of secreted antibodies from fully
      differentiated plasma cells. Regulation of these events has been attributed
      primarily to two cis-elements that work from long distances on their target
      sequences, i.e., an ~1 kb intronic enhancer, EMU, located between the V region
      segments and the most 5' constant region gene, CMU; and an ~40 kb 3' regulatory
      region (3' RR) that is located downstream of the most 3' C(H) gene, Calpha. The
      3' RR is a candidate for an "end" of B cell-specific regulation of the Igh locus.
      The 3' RR contains several B cell-specific enhancers associated with DNase I
      hypersensitive sites (hs1-4), which are essential for CSR and for high levels of
      IgH expression in plasma cells. Downstream of this enhancer-containing region is
      a region of high-density CTCF binding sites, which extends through hs5, 6, and 7
      and further downstream. CTCF, with its enhancer-blocking activities, has been
      associated with all mammalian insulators and implicated in multiple chromosomal
      interactions. Here we address the 3' RR CTCF-binding region as a potential
      insulator of the Igh locus, an independent regulatory element and a predicted
      modulator of the activity of 3' RR enhancers. Using chromosome conformation
      capture technology, chromatin immunoprecipitation, and genetic approaches, we
      have found that the 3' RR with its CTCF-binding region interacts with target
      sequences in the V(H), EMU, and C(H) regions through DNA looping as regulated by
      protein binding. This region impacts on B cell-specific Igh processes at
      different stages of B cell development.

PMID- 23162574
TI  - Dental management in dysphagia syndrome patients with previously acquired brain
      damages.
AB  - Dysphagia is defined as difficulty in swallowing food (semi-solid or solid),
      liquid, or both. Difficulty in swallowing affects approximately 7% of population,
      with risk incidence increasing with age. There are many disorder conditions
      predisposing to dysphagia such as mechanical strokes or esophageal diseases even
      if neurological diseases represent the principal one. Cerebrovascular pathology
      is today the leading cause of death in developing countries, and it occurs most
      frequently in individuals who are at least 60 years old. Swallowing disorders
      related to a stroke event are common occurrences. The incidence ranging is
      estimated from 18% to 81% in the acute phase and with a prevalence of 12% among
      such patients. Cerebral, cerebellar, or brain stem strokes can influence
      swallowing physiology while cerebral lesions can interrupt voluntary control of
      mastication and bolus transport during the oral phase. Among the most frequent
      complications of dysphagia are increased mortality and pulmonary risks such as
      aspiration pneumonia, dehydration, malnutrition, and long-term hospitalization.
      This review article discusses the epidemiology of dysphagia, the normal
      swallowing process, pathophysiology, signs and symptoms, diagnostics, and dental
      management of patients affected.

PMID- 23162576
TI  - Evaluation of the therapeutic effects of Aloe vera gel on minor recurrent
      aphthous stomatitis.
AB  - BACKGROUND: Aphthous ulcer is one of the most common diseases of the oral cavity
      with no known effective treatment so far, which could cause severe discomfort in
      patients. Aloe vera (A.V.) is a tropical plant with anti-inflammatory and
      immunostimulant effects, which could be of benefit in a diversity of wound
      healing conditions. The aim of this study is to evaluate topically administered
      A.V. gel on oral cavity minor aphthous healing. MATERIALS AND METHODS: As a
      double-blind (case control) clinical trial, 40 patients with oral minor aphthous
      lesions were randomly allocated in either the case group (A.V. gel) or the
      control (placebo) group. The healing time (days after gel application), patient's
      pain score; the lesion and its surrounding inflammation diameters were recorded
      for 2 weeks. The obtained results were analyzed by either "Fishers exact" or t
      student test using SPSS software. RESULTS: The mean (+/-SD) of patients' age was
      29.25 +/- 8.48 and 27.95 +/- 7.96 years in the control and A.V.-treated groups,
      respectively, which were not significantly different (P > 0.05). The duration of
      complete wound healing, pain score, wound size and inflammation zone diameter in
      the A.V.-treated group were significantly lower than the control group (P <=
      0.05) on specific time points after treatment. CONCLUSION: It seems likely that
      A.V. 2% oral gel is not only effective in decreasing the recurrent aphthous
      stomatitis patients' pain score and wound size but also decreases the aphthous
      wound healing period.

PMID- 23162575
TI  - Association of pregnant women periodontal status to preterm and low-birth weight
      babies: A systematic and evidence-based review.
AB  - The mouth serves as a mirror to general health and also as a portal for disease
      to the rest of the body. Since the old wives' tale of "the loss of a tooth for
      every pregnancy", oral health during pregnancy has long been a focus of interest.
      In the past decade, there has been mounting scientific evidence suggesting that
      periodontal disease may play an important role as a risk factor for adverse
      pregnancy outcomes. Considering all the above stated factors this systematic
      review is aimed to focus on the association of periodontal diseases to preterm
      and low-birth weight (LBW) babies. In view of the large body of literature the
      review is limited to studies identified by computer searching. Hand searching of
      journals and gathering of unpublished reports and conference proceedings was
      outside the scope of the review. The PubMed database was searched using the
      search terms: periodontitis, preterm, LBW. The titles, authors, and abstracts
      from all studies identified by the electronic search were printed and reviewed
      independently on the basis of keywords, title and abstract, to determine whether
      these met the inclusion criteria. The electronic search identified 68 papers.
      After review of the study title, keywords and abstracts, 62 papers were
      identified potentially meeting inclusion criteria. Generally, all the studies
      reviewed in the paper suggest that periodontal disease may be a potential risk
      factor for preterm LBW babies.

PMID- 23162577
TI  - Oral health knowledge, attitude and practices among health professionals in King
      Fahad Medical City, Riyadh.
AB  - BACKGROUND: The aim of this study was to assess the oral health knowledge,
      attitude and practices among the health care professionals working at KFMC,
      Riyadh. MATERIALS AND METHODS: A cross-sectional study of 161 health
      professionals consisting of doctors, nurses, pharmacists, technicians and medical
      students was carried out using a structured, self-administered, close-ended
      questionnaire. Responses were collected and descriptive statistics, ANOVA, Chi
      square tests and z-tests were performed. RESULTS: Doctors showed a high mean
      knowledge score as compared with other health professionals. Comparison of oral
      health knowledge scores among the different types of health professionals yielded
      statistically significant differences (P < 0.05). The attitude toward visit to
      the dentist varied; 52.7% of nurses and 50% of technicians said that they would
      like to visit the dentist regularly. 66.7% of the medical students visit the
      dentist whenever they get pain in their tooth. 54.5% doctors and 45.8%
      pharmacists are likely to visit the dentist occasionally. For 60% medical
      students, tooth ache was the driving factor for their last visit. Majority of the
      health professionals said that the fear of drilling was the main reason for
      avoiding the dentist. Almost all the health professionals said that they cleaned
      their tooth by toothbrush and toothpaste. Less than 50% of the health
      professionals used mouth wash and dental floss. Less than 10% used Miswak and
      toothpick as part of their oral hygiene. CONCLUSION: Oral health knowledge among
      the health professionals working in KFMC, Riyadh was lower than what would be
      expected of these groups, which had higher literacy levels in health care, but
      they showed a positive attitude toward professional dental care.

PMID- 23162579
TI  - Effect of different decontamination procedures from a saliva-contaminated cured
      bonding system (Single Bond).
AB  - BACKGROUND: A few studies have investigated the effect of saliva contamination of
      cured or uncured adhesive systems. The aim of this study was to compare the
      effect of different decontamination methods on the shear bond strength of
      composite to enamel and dentin using an adhesive contaminated after light
      activation. MATERIALS AND METHODS: In this in vitro experimental study, 80
      extracted sound human teeth, 40 premolars and 40 central incisors were selected
      for dentin and enamel specimen preparation. Within each of the two test groups,
      the teeth were randomly subdivided into five groups. The materials used consisted
      of single bond (3M) and Z250 (3M). Except group 1 (Control), in Groups 2-5, cured
      adhesive was contaminated with saliva (20 s). Decontaminating procedures were
      rinsing, blot-drying, rebonding (Group 2), rinsing, air-drying, rebonding (Group
      3), etching, rinsing, blot-drying, rebonding (Group 4) and etching, rinsing, blot
      drying (Group 5). Then, composite resin was inserted on the treated surfaces and
      cured. The results were subjected to one-way ANOVA and Tukey honestly significant
      difference (HSD) tests. RESULTS: Group 5 (etching, rinsing, blot drying) resulted
      in significantly lower bond strength to both enamel and dentin surfaces in
      comparison with the other groups (P < 0.05). CONCLUSION: When the adhesive was re
      applied, all decontamination methods in this study seemed sufficient to decrease
      the adverse effect of saliva.

PMID- 23162578
TI  - Orthodontic cements induce genotoxicity and cytotoxicity in mammalian cells in
      vitro.
AB  - BACKGROUND: This study assessed the genotoxic and cytotoxic potential of three
      different glass ionomer cements used in Orthodontics (Vidrion C, OptiBand, and
      Band-Lok). MATERIALS AND METHODS: The tested cements were exposed in vitro to
      mouse fibroblast cells for 1 h at 37 degrees C. The genotoxicity and cytotoxicity
      were evaluated by means of the single cell gel (Comet Assay) and the trypan blue
      exclusion test, respectively. All data were assessed by the Kruskal-Wallis non
      parametric test, followed by Dunn's test. P < 0.05 was considered for statistical
      significance. RESULTS: Significant statistically differences (P < 0.05) in
      cytotoxicity were observed for both Vidrion C powder and liquid at the tested
      concentrations, with exception to the group presenting the lowest powder
      concentration. OptiBand similarly presented induced cellular death at the highest
      tested concentration for paste A (P < 0.05). Band-Lok paste B was also able to
      induce cytotoxicity at the highest tested concentration. Regarding the comet
      assay, Band-Lok paste B and OptiBand paste A resulted in increased DNA injury (P
      < 0.05). CONCLUSION: The obtained results support the thought that some glass
      ionomer cement components present both genotoxic and cytotoxic effects when in
      high concentrations. Since DNA damage and cellular death are important events
      during oncogenesis, this study represents relevant contribution to estimate the
      real risks induced by these materials upon cellular systems.

PMID- 23162580
TI  - Interest and satisfaction of dentists in practicing periodontics: A survey based
      on treatment of gingival recession.
AB  - BACKGROUND: Gingival recession is a common occurrence and patients often report
      to dental clinic with associated problems such as root surface hypersensitivity,
      esthetic concerns, cervical root abrasions, and root caries that make it a
      concern for patients. Based upon the fact that gingival recession is an enigma
      for clinicians because of multitude of etiological factors and plethora of
      treatment modalities present for its treatment, a survey was conducted to assess
      knowledge as well as opinion about most common etiology, classification, and
      preferred treatment of gingival recession and to evaluate the interest and
      satisfaction of dentists in practicing periodontics. MATERIALS AND METHODS: Study
      design consisted of a cross-sectional online survey, conducted among dentists
      practicing in state of Punjab, India, in the month of April 2011. A structured
      online questionnaire consisting of 17 questions evaluating the interest of
      dentists in periodontics based on knowledge about gingival recession (most of
      them giving the possibility of multiple choices of answers) was sent to about 300
      dentists. Pearson Chi-Square and Mann-Whitney U tests were used for statistical
      analysis of data collected. P <= 0.05 was considered as statistically significant
      and P <= 0.01 considered as highly significant. RESULTS: A greater proportion of
      periodontists had better knowledge about etiology (P = 0.07), classification (P =
      0.000), and treatment of gingival recession (P = 0.000). A greater number of
      periodontists opted for the surgical modalities to correct the defects produced
      by gingival recession as compared to non-periodontists and had better interest (P
      = 0.000) and satisfaction (P = 0.000) in practicing periodontics. CONCLUSION: The
      results elucidated that periodontists had better interest and satisfaction in
      practicing periodontics, and were more inclined towards surgical correction of
      gingival recession as compared to non-periodontists.

PMID- 23162581
TI  - An analysis of postoperative complications and efficacy of 3-D miniplates in
      fixation of mandibular fractures.
AB  - BACKGROUND: Recently, various modifications in transorally placed miniplates for
      direct fixation of the mandibular fracture are gaining popularity. The
      modifications have various advantages like more rigidity, less foreign material,
      less time in application, etc. Among the various modifications of miniplates,
      three-dimensional (3-D) plating system is also gaining popularity. Thus, in the
      present study, we tried to evaluate the efficacy and postoperative complications
      of 3-D titanium miniplates in the treatment of mandibular fractures. MATERIALS
      AND METHODS: A prospective study was conducted on 40 patients with non-comminuted
      mandibular fractures. They were treated using a 2-mm 3-D titanium miniplate
      through intraoral approach. All patients were systematically monitored 6 months
      postoperatively. Outcome parameters like infection, hardware failure, wound
      dehiscence, sensory disturbance of the inferior alveolar nerve, occlusion, and 3
      D plate stability were recorded. The statistical tests used in study were mean,
      standard deviation, and Chi-square test. P values less than 0.05 were considered
      significant and values less than 0.001 were considered very highly significant.
      RESULTS: Two patients had a postoperative infection with no consequences. All
      patients had normal sensory function 3 months after surgery. Plate fracture had
      not occurred in any patient. Occlusal was normal and wound dehiscence was not
      reported. 3-D plate was stable in all the patients. CONCLUSIONS: It was seen that
      3-D titanium miniplates were effective in the treatment of mandibular fractures
      and overall complication rates were lesser. In symphysis and parasymphysis
      regions, 3-D plating system uses lesser foreign material than the conventional
      miniplates using Champy's principle.

PMID- 23162582
TI  - Effect of the combination of enamel matrix derivatives and deproteinized bovine
      bone materials on bone formation in rabbits' calvarial defects.
AB  - BACKGROUND: Various types of materials are used in bone regeneration procedures.
      The aim of this study was to investigate the use of the enamel matrix derivative
      (EMD), deproteinized bovine bone mineral (Bio-Oss), and a combination of Bio-Oss
      plus EMD in the treatment of bone defects created in the rabbits' calvaria.
      MATERIALS AND METHODS: Twenty New Zealand white rabbits were included in this
      experimental randomized single blind study. Four equal cranial bone defects (3 *
      6 * 0.5 mm(3)) were created in frontal and parietal bone and randomly grafted
      with Bio-Oss (Group 1), EMD (Group 2), EMD + Bio-Oss (Group 3) and one of them
      was left unfilled to serve as a control group (Group 4). After 2, 4, 8, and 12
      weeks the defects were evaluated by using histological and histomorphometric
      analysis. Data were analyzed by the Bonferroni test using SPSS 13 statistical
      software. P value <0.05 considered as statistically significant level. RESULTS:
      Bone formation in the EMD + Bio-Oss group after 2 weeks was diminished when
      statistically compared to the other groups (P < 0.05). Bone augmentation after 4
      weeks from the lowest to the highest were found in groups 1, 3, 2, and 4,
      respectively, and these differences were statistically significant (P < 0.05).
      Using EMD with Bio-Oss increased bone formation in the non-critical defects in
      the rabbit calvaria during 8 and 12 weeks (P < 0.05). CONCLUSIONS: Boosting of
      EMD plus Bio-Oss seems to have synergic effect on bone regeneration in bone
      defects.

PMID- 23162583
TI  - Evaluation of IL-8 gene polymorphisms in patients with periodontitis in Hamedan,
      Iran.
AB  - BACKGROUND: Many environmental and genetic factors are known as factors that
      increase the susceptibility to periodontitis. As IL-8 is a chemokine that mediate
      the inflammatory process in periodontal disease, we decided to evaluate the
      effect of its polymorphism on chronic and aggressive periodontitis. MATERIALS AND
      METHODS: In this cross-sectional study DNA was isolated from the whole blood of
      107 periodontitis patients and 199 healthy individuals. All samples were
      genotyped for the IL-8 polymorphisms using the polymerase chain reaction with
      sequence specific primers. The distribution of the interleukin-8 genotype and
      allele frequencies in control and disease groups was analyzed by the Chi-square
      test and a P-value of < 0.05 was considered statistically significant. RESULTS:
      The findings revealed that the allele and genotype frequencies of A2767T,
      T(1)1722T(2), and C781T polymorphism of IL-8 gene were not significantly differed
      between controls and patients. However, there was a significant difference in the
      genotype frequencies of IL-8 A251T (P < 0.0001), G396T (P < 0.0001), and C1633T
      (P < 0.0001) gene polymorphism between the patient and the control groups.
      Additionally, there was a significant difference in the genotype frequencies of
      C1633T (P < 0.05) polymorphism of IL-8 gene between the aggressive and chronic
      periodontitis. CONCLUSION: IL-8 gene polymorphism may be protective against
      periodontitis.

PMID- 23162584
TI  - Determining the effect of implant surgery on blood oxygen saturation of the
      adjacent tooth.
AB  - BACKGROUND: Implant surgery requires local anesthesia and drilling. This surgery
      may affect the blood circulation of the adjacent teeth. In this study, we
      evaluated the blood oxygen saturation of the healthy adjacent tooth with a pulse
      oximeter, during implant surgery. MATERIALS AND METHODS: In this clinical trial
      study, 15 healthy adult patients, who were candidates for anterior implant
      surgery and had healthy anterior adjacent teeth, were selected. Blood oxygen
      saturation of the adjacent tooth and index finger was measured with a pulse
      oximeter, before and after local anesthetic injection, and also immediately and
      one hour after completion of surgery. The collected data were analyzed with a
      Paired Samples Test and Spearman's Correlation Coefficient. (the significance
      level was at alpha P < 0.05). RESULTS: The mean value of peripheral finger blood
      Spo(2) before local anesthetic injection was 98.2% and remained stable during
      surgery. In the adjacent tooth, the mean values of the pulpal Spo(2), before and
      after local anesthesia, were 87.73 and 79.27%, respectively; immediately after
      surgery it was 86.13% and one hour after surgery was 86.4%. The decrease in the
      value of pulpal Spo(2) after local anesthesia compared to before the injection
      was significant. Also there was an inverse relationship between the numbers of
      utilized local anesthetic cartridges and the value of pulpal Spo(2) after local
      anesthesia. CONCLUSION: After giving local anesthesia, the mean value of Spo(2)
      in the adjacent tooth, because of the vasoconstructive effect of epinephrine, was
      decreased to about 8%. According to this study, the effect of the local
      anesthetic drug, containing epinephrine, on the blood circulation in the adjacent
      tooth was significantly more than the trauma from the implant surgery. We wonder
      if this temporary decrease in blood flow in the adjacent toot is clinically
      important or not. To answer this question more studies are required.

PMID- 23162585
TI  - Influence of local anesthetics with or without epinephrine 1/80000 on blood
      pressure and heart rate: A randomized double-blind experimental clinical trial.
AB  - BACKGROUND: Local anesthesia (LA) with epinephrine have an important role in pain
      and bleeding control. However, most clinicians believe LA + epinephrine may cause
      rapid raise in blood pressure (BP) and heart rate (HR). The aim of this research
      was to compare the changes in HR and BP after administration of lidocaine with
      and without epinephrine 1/80000 in two infiltration (INF) and inferior alveolar
      nerve block methods (IANB). MATERIALS AND METHODS: The study was a randomized
      double-blind experimental clinical trial. Forty subjects were divided into two
      equal groups and two subgroups. In one group, INF and in the other group, IANB
      were used and, further, in one subgroup lidocaine and in another subgroup,
      lidocaine plus epinephrine were used. BP and HR were recorded before and 10 min
      after. The paired t-test for intragroup differences and independent t-test for
      intergroup analysis were used at the significant level of P<=0.05. RESULTS: The
      mean BP and HR values were reduced after injection of lidocaine in both INF and
      IANB compared with baseline. The differences were statistically significant (P <
      0.05), but, on comparing these values between the two injection methods, the
      differences were not statically significant (P = 0.089 and 0.066, respectively).
      The mean BP and HR values were increased after injection of lidocaine plus
      epinephrine in both INF and IANB compared with baseline, and these were
      statistically significant (P < 0.05) but, on comparing these values between the
      two methods, the differences were not statically significant (P = 0.071 and
      0.092, respectively). CONCLUSION: The rise in BP and HR following injection of
      lidocaine plus epinephrine was statistically significant compared with baseline
      in both INF and IANB, but this was not clinically and numerically considerable.

PMID- 23162586
TI  - Comparison of color stability of a composite resin in different color media.
AB  - BACKGROUND: Color change of composite restorations in different color media
      during the time is a common problem in esthetic dentistry, causing the need to
      replace the restoration, and spending a great deal of cost and time to patients.
      The aim of this study is to investigate the effects of different common drinks
      consumed by patients on one of the widely used composites in dentistry. MATERIALS
      AND METHODS: Sixty-five disk-shaped specimens were prepared with a light-cured
      composite (Z100-shade A2) and divided into five groups of 13 specimens. Samples
      of each group were immersed in staining solutions (tea, coffee, lemonade, and
      cola) and distilled water (as control). Color values (L*, a*, b*) were measured
      relative to the standard illuminant D65 over a white background, using the CIE
      L*a*b* system. Color change values were calculated before and after 1, 7, and 14
      days of immersion. Repeated measures and one-way analysis of variance (ANOVA) and
      paired t tests were applied for statistical analysis. RESULTS: Tea and coffee
      produced the most discoloration, whereas, water exhibited the least color change
      after immersion for 14 days in Z100 (P < 0.05). After one day of immersion,
      coffee caused the lowest discoloration in the test composite, compared to tea,
      cola, distilled water, and lemonade (P < 0.05). CONCLUSION: Staining solutions
      and immersion time are significant factors that affect color stability of
      composite resins.

PMID- 23162587
TI  - A processing method for orthodontic mini-screws reuse.
AB  - BACKGROUND: The possibility of mini-screws reuse would reduce treatment cost. The
      aim of this study is to introduce a new method (application of phosphoric acid
      37% for 10 minutes followed by sodium hypochlorite 5.25% for 30 minutes) for
      cleansing of mini-screws and assessing the efficacy of this method. The effects
      of this processing on the insertion, removal, and fracture torques of mini-screws
      were evaluated. MATERIALS AND METHODS: This experimental study was done in two
      parts. In part I the amount of calcium ion on mini-screws surfaces as an index of
      tissue remnants was assessed. In part II of this study, the effects of previous
      use, processing method, and resterilization on the insertion, removal, and
      fracture torques of mini-screws were assessed. Each part of this study had 3
      groups; non-processed used (NP), processed used (P), and as-received (C). Each
      group had 16 samples in part I and 20 samples. Non parametric statistical tests
      were used in part I and one way ANOVA in part II. RESULTS: The mean amount of
      calcium ion in groups non-processed (NP1), processed (P1), and control (C1) were
      4.7, 0.43, and 0.02 ppm, respectively. The amount of calcium ion in group NP1 was
      significantly greater than in the other groups (P = 0.000), but the difference
      between groups P1 and C1 was not significant (P = 0.087). The mean insertion
      torque of group NP2 was lower than that of other groups (P < 0.05) but P2 and C2
      did not have significant differences (P = 0.988). The mean of removal and
      fracture torque did not have significant differences among all groups.
      CONCLUSION: Cleaning of used mini-screws with phosphoric acid 37% (10 minutes)
      and sodium hypochlorite 5.25% (30 minutes) reduces tissue remnants to the level
      of as-received mini-screws. So it can be suggested as a processing method of used
      mini-screws. Previous insertion of mini-screws into the bone and above-mentioned
      processing method and resterilization with autoclave had no adverse effects on
      insertion, removal, and fracture torque values as mechanical properties indices.

PMID- 23162588
TI  - In vitro evaluation of the effect of deproteinization on the marginal leakage of
      resin restorations using three bonding agents.
AB  - BACKGROUND: The perfect sealing of the tooth/restoration interface is important
      to prevent bacteria penetration that may lead to secondary caries and also, when
      dentin is involved, prevent excessive fluid movement in the dentinal tubules that
      may cause hypersensitivity. The aim of this study was to evaluate the effect of
      deproteinization and application of reducing agent on the marginal integrity of
      composite restorations using three different bonding agents (Prime & Bond NT,
      AdheSE and G-Bond). MATERIALS AND METHODS: Class V cavities were prepared on the
      buccal surface of 90 recently extracted human premolars and were divided into
      three groups (I, II, and III) based on the adhesives. Each group was subdivided
      into three subgroups of 10 each according to the surface treatment: application
      according to clinical protocol; etching with 37% phosphoric acid for 15
      seconds/5% NaOCl; 10% sodium ascorbate after etching/NaOCl. The cavities were
      restored with Filtek Z 350 nanocomposite. The specimens were sectioned and
      evaluated under stereomicroscope. The morphology of the resin-dentin interface
      was visualized using SEM. Statistical analysis was done using Kruskal-Wallis one
      way ANOVA followed by a Mann-Whitney U- test (P<0.05). RESULTS: Group I showed
      significantly least microleakage among the groups. No significant difference in
      microleakage was found between groups I and II. Within the subgroups for each
      group, no significant difference in microleakage scores was observed. SEM
      micrographs presented gap free areas in group I and varying degrees of gaps in
      the other two groups. CONCLUSION: Etch and rinse adhesives were tenable for
      deproteinization than self etch adhesives.

PMID- 23162589
TI  - An in vitro microleakage study of class V cavities restored with a new self
      adhesive flowable composite resin versus different flowable materials.
AB  - BACKGROUND: Regarding the importance of sealing ability of restorative dental
      materials, this study was done to assess the microleakage of class V cavities
      restored with a new self-adhesive flowable composite resin and compare to
      different flowable materials. MATERIALS AND METHODS: Seventy standardized class V
      cavities were prepared on the buccal surface of maxillary premolars teeth. The
      occlusal and the gingival margins of the cavities were located on the enamel and
      cementum/dentin, respectively. Teeth were randomly assigned into five groups (n =
      14) and restored with different flowable materials following the manufacturer's
      instructions: groups I and II: EMBRACE WetBond flowable composite resin with and
      without acid etching and bonding agent, respectively; group III: flowable
      compomer (Dyract Flow); and IV and V: microhybrid (Tetric Flow) and nanofilled
      (Premise Flowable) flowable composite resins, respectively. After finishing and
      polishing, the teeth were stored in distilled water at 37 degrees C,
      thermocycled, coated with nail varnish, and immersed in a basic fuchsin, and then
      longitudinally sectioned. Dye penetration was examined with a stereomicroscope
      and scored separately for occlusal and gingival on a 0-3 ordinal scale. Data were
      analyzed with Kruskal-Wallis, Mann-Whitney and Wilcoxon tests (alpha=0.05).
      RESULTS: EMBRACE WetBond with acid etching and bonding agent had significantly
      less microleakage at the occlusal margins than those without, but not at cervical
      margins. Also cavities restored with EMBRACE WetBond without acid etching and
      bonding agent showed significantly greater microleakage scores than other groups
      at occlusal margin, but there was no significant difference at the cervical
      margin. CONCLUSION: The application of acid etching and bonding agent with
      EMBRACE WetBond provided better occlusal marginal sealing than those without at
      class V cavities.

PMID- 23162590
TI  - The effects of different concentrations of chlorhexidine gluconate on the
      antimicrobial properties of mineral trioxide aggregate and calcium enrich
      mixture.
AB  - BACKGROUND: The aim of this study was to evaluate the antimicrobial activity of
      Mineral Trioxide Aggregate (MTA) and Calcium Enrich Mixture) CEM (mixed with
      different concentrations of chlorhexidine (CHX). MATERIALS AND METHODS: Cements
      used in this in vitro study included Gray proRoot MTA and CEM with the
      microorganisms being entrococcus faecalis, streptococcus muntas, Candida
      albicans, Actinomyces, Escherichia coli, and a mixture of these microorganisms.
      CHX was used in the form of liquid at 0.2%, 2%, and 0.12% concentrations. Contact
      dilution and colony count method was used to evaluate the antibacterial activity
      of these cements. After 0, 24, 48, 72, and 96-hour intervals, we cultured the
      samples on blood agar medium. Colonies were counted after incubation at 37
      degrees . Data were statistically analyzed by a Kruskal-Wallis test to compare
      the antimicrobial activity of MTA and CEM. RESULTS: All concentrations of CHX
      were mixed with MTA and the CEM had antibacterial activities on all
      microorganisms' strains except for the Enterococcus faecalis and the mixture
      group. MTA had better antibacterial activity than the CEM, but this difference
      was not significant (P = 0.13). The mixing of MTA and the CEM with CHX
      significantly increased the antibacterial properties of both cements (P < 0.03).
      There was no statistically significant difference between the different
      concentrations of CHX. The antibacterial activity of the materials increased
      through time. CONCLUSION: The mixture of MTA and CEM with different concentration
      of CHX significantly increased the antibacterial activity.

PMID- 23162591
TI  - Enamel resistance to demineralization following Er:YAG laser etching for bonding
      orthodontic brackets.
AB  - BACKGROUND: Several studies have shown that laser-etching of enamel for bonding
      orthodontic brackets could be an appropriate alternative for acid conditioning,
      since a potential advantage of laser could or might be caries prevention. This
      study compared enamel resistance to demineralization following etching with acid
      phosphoric or Er:YAG laser for bonding orthodontic brackets. MATERIALS AND
      METHODS: Fifty sound human premolars were divided into two equal groups. In the
      first group, enamel was etched with 37% phosphoric acid for 15 seconds. In the
      second group, Er:YAG laser (wavelength, 2 940 nm; 300 mJ/pulse, 10 pulses per
      second, 10 seconds) was used for tooth conditioning. The teeth were subjected to
      4-day PH-cycling process to induce caries-like lesions. The teeth were then
      sectioned and the surface area of the lesion was calculated in each
      microphotographs and expressed in pixel. The total surface of each specimen was
      196 608 pixels. RESULTS: Mean lesion areas were 7 171 and 7532 pixels for Laser
      etched and Acid-etched groups, respectively. The two sample t-test showed that
      there was no significant difference in lesion area between the two groups (P =
      0.914). CONCLUSION: Although Er:YAG laser seems promising for etching enamel
      before bonding orthodontic brackets, it does not reduce enamel demineralization
      when exposed to acid challenge.

PMID- 23162592
TI  - Evaluation of efficacy of restorative dental treatment provided under general
      anesthesia at hospitalized pediatric dental patients of Isfahan.
AB  - BACKGROUND: General anesthesia (GA) allows dental treatment to be rendered under
      optimal conditions, theoretically ensuring ideal outcomes. The aim of this study
      was to determine the efficacy of restorative dental procedures performed under
      GA. MATERIALS AND METHODS: In this cross-sectional retrospective study, 305
      pediatric patients who had been treated under GA 6 to 24 months before our survey
      at Isfahan's hospitalized dentistry center were examined. The examination was
      performed on dental chair with oral mirror and dental probe. The results were
      recorded in a special form for each patient for statistical analysis and
      evaluation of restorations to be successful or failed. Statistical analysis was
      performed by chi-square and fisher exact tests for comparison between success
      rates of restorations and Kendall's tau-b test for evaluating the effect of time
      on success rates of them (P < 0.05). RESULTS: Stainless steel crown restorations
      had significantly better results vs class I and class II amalgam and class I and
      class II tooth color restorations. All types of posterior tooth color
      restorations had statistically same results with amalgam restorations. Anterior
      composite resin build-up represented significantly low success rates. The failure
      rates of stainless steel crown and anterior composite resin build-up restorations
      did not correlate with the time of follow-up (P = 0.344 and P = 0.091,
      respectively). CONCLUSION: Stainless steel crown restorations had significantly
      better results vs other posterior restorations. The failure rates of stainless
      steel crown and anterior composite resin build-up restorations did not correlate
      with the time of follow-up in comparison of other restorations.

PMID- 23162593
TI  - Neurofibromatosis type I (von Recklinghausen's disease): A family case report and
      literature review.
AB  - The term neurofibromatosis (NF) is used for a group of genetic disorders that
      primarily affect the cell growth of neural tissues. Neurofibromatosis type 1
      (NF1), also known as von Recklinghausen's disease, is the most common type of NF,
      and accounts for about 90% of all cases. It is one of the most frequent human
      genetic diseases, with a prevalence of one case in 3,000 births. 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 the NF1 patients. The aim of this article is to report the NF1
      in a family with different manifestations and to review the literature.

PMID- 23162594
TI  - Dentinogenesis imperfecta associated with osteogenesis imperfecta.
AB  - This paper presents a case with dentinogenesis imperfecta (DI) associated with
      osteogenesis imperfecta. Systemic and dental manifestations of OI and its medical
      and dental treatments are discussed in this paper. A 5-year-old child with the
      diagnosis of OI was referred to the Dental School of Shaid Beheshti University of
      Medical Sciences. On clinical examination yellow/brown discoloration of primary
      teeth with the attrition of the exposed dentin and class III malocclusion was
      observed. Enamel of first permanent molars was hypoplastic. Radiographic
      examinations confirmed the diagnosis of DI. A histological study was performed on
      one of the exfoliating teeth, which showed abnormal dentin. Primary teeth with DI
      were more severely affected compared to permanent teeth; enamel disintegration
      occurred in teeth with DI, demonstrating the need for restricts recalls for these
      patients.

PMID- 23162595
TI  - An atypical presentation of Pindborg tumor in anterior maxilla.
AB  - Pindborg tumor, the eponymous counterpart of calcifying epithelial odontogenic
      tumor (CEOT), is a rare benign odontogenic neoplasm that was first described by a
      Dutch pathologist Jens Jorgen Pindborg in 1955 and accounts for approximately 1%
      of all odontogenic tumors. Its origin as well as its malignant potential is
      controversial. This neoplasm is possibly of stratum intermedium origin and
      occurring predominantly in the mandible of adults. We hereby report a case of
      Pindborg tumor arising in the premaxilla which is seldom (9 out of 200 cases)
      documented in the scientific literature.

PMID- 23162597
TI  - White tea: A contributor to oral health.

PMID- 23162596
TI  - Intraosseous polymorphous low-grade adenocarcinoma of mandible: A rare entity.
AB  - Polymorphous low-grade adenocarcinoma is a rare type of minor salivary gland
      malignancy. The characteristic features of these tumors are the varied
      histomorphology and the malignant, albeit indolent behavior. It occurs commonly
      in the minor salivary glands, with the palate (58.5%) being the most common intra
      oral site. Maxillary area (2%), mandibular mucosal area (1.5%) and posterior
      trigone region (0.5%) are the least affected areas. An occasional case has been
      reported arising from an intraosseous location i.e the maxilla, and only two
      cases have been reported in the English literature originating from the mandible.
      One such very rare case of polymorphous low-grade adenocarcinoma of the mandible,
      which radiographically has a soap bubble appearance, is reported here.

PMID- 23162598
TI  - Coincidental occurrence of hepatocellular carcinoma and cholangiocarcinoma
      (collision tumors) after liver transplantation: a case report.
AB  - Coincidental occurrence of hepatocellular carcinoma (HCC) and cholangiocarcinoma,
      known as "collision tumors", within a cirrhotic liver is rare. Herein, we report
      a case of liver transplantation (LT) in a patient with such collision tumors. Our
      patient was a 56-year-old woman with hepatitis C virus-related cirrhosis and 2
      focal hepatic lesions, measuring 1.5 and 3 cm, in the liver segments 8 and 5,
      respectively. The lesion on segment 8 showed the typical radiological
      characteristics of HCC; however, the lesion in segment 5 showed an atypical
      vascular pattern and was closely associated with the inferior vena cava. Serum
      alpha-fetoprotein level was normal and serum carbohydrate antigen 19-9 (CA19-9)
      level was slightly elevated (63 U/mL); the extrahepatic spread of HCC was ruled
      out. The patient underwent an uneventful deceased-donor LT. Histopathological
      examination of the explant confirmed that the lesion on segment 8 was an HCC, but
      surprisingly, the lesion on segment 5 was found to be a cholangiocarcinoma. Six
      months after LT, the serum CA19-9 level was markedly elevated (255 U/mL), and the
      patient began experiencing abdominal pain. Magnetic resonance imaging showed
      enlarged hilar and paraaortic lymph nodes that were suggestive of metastases;
      histopathological analysis using ultrasound (US)-guided biopsy confirmed
      recurrent cholangiocarcinoma. Unfortunately, the patient died because of tumor
      recurrence 9 months after LT.Collision tumor resulting from the co-existence HCC
      and cholangiocarcinoma in a cirrhotic liver is rare and has a negative impact on
      the outcome of LT. Atypical vascular pattern and elevated serum CA19-9 levels are
      suggestive of such tumors; patients with these findings should undergo a targeted
      biopsy to rule out the coincidental occurrence of HCC and cholangiocarcinoma.

PMID- 23162599
TI  - Risk of hepatocellular carcinoma in workers exposed to chemicals.
AB  - CONTEXT: Studies on experimental animals have shown liver is a common target of
      chemical carcinogens; this might suggest that occupational exposure to chemicals
      is another risk factor for HCC. However, the relationship between occupation and
      liver cancer has not been extensively studied, with the exception of the known
      association between vinyl chloride and angiosarcoma of the liver. EVIDENCE
      ACQUISITION: A MEDLINE and conventional search of the past 50 years of the
      medical literature was performed to identify relevant articles on incidence and
      mechanisms of HCC due to occupational exposure to chemicals. Several important
      edited books and monographs were also identified and reviewed. RESULTS: While
      laboratory data clearly indicate that the liver is an important target of
      chemical carcinogenesis, epidemiological studies provide very limited evidence on
      occupational risk factors for HCC. Nevertheless, we found some case reports and
      epidemiological data showing a moderately increased risk of HCC development in
      people exposed to vinyl chloride, organic solvents, pesticides, polychlorinated
      biphenyls, and arsenic. CONCLUSIONS: Occupational exposure to chemicals may be
      another risk factor for HCC development, but the interpretation of currently
      available findings is limited by the small number of studies, questionable
      accuracy of the diagnosis of liver cancer, and potential confounding or modifying
      factors such as chronic hepatitis virus infection and alcohol consumption.
      Further relevant investigations are required for clarifying the actual
      contribution of occupational exposure to chemicals in HCC development.

PMID- 23162600
TI  - Recent advances in radiofrequency ablation for the management of hepatocellular
      carcinoma.
AB  - CONTEXTS: Hepatocellular carcinoma (HCC) is one of the most common malignant
      diseases in the world. Because less than 20% of patients with HCC are resectable,
      various types of non-surgical treatment have been developed. EVIDENCE
      ACQUISITION: At present, radiofrequency ablation (RFA) is accepted as the
      standard local treatment for patients with HCC because of its superior local
      control and overall survival compared to other local treatments. RESULTS: New
      devices for RFA and combination treatments of RFA with other procedures have been
      developed to improve anti-tumoral effects. CONCLUSIONS: This review mainly
      focuses on the status of RFA in the management of HCC and recent advances in RFA
      treatment technology.

PMID- 23162601
TI  - An overview of biomarkers for the diagnosis of hepatocellular carcinoma.
AB  - CONTEXT: Primary liver cancer is one of the most common and deadly malignant
      neoplasms worldwide. The incidence and mortality rates for hepatocellular
      carcinoma (HCC) are virtually identical, reflecting the poor overall survival of
      patients with this kind of tumor. Effective therapies mostly achieved if the HCC
      diagnosis is made at early stages of the tumor. Surveillance tests include
      serologic and radiologic examinations. EVIDENCE ACQUISITION: In this review, an
      overview of biomarkers for the diagnosis of HCC and future challenges in this
      popular field has been presented. RESULTS: Serum tumor markers, such as alpha
      fetoprotein (AFP) and des-gammacarboxy prothrombin (DCP) are commonly used for
      the surveillance, but their roles have been intensely debated despite the
      existence of sensitive radiologic tests. Most HCC-related cancer biomarkers are
      involved in chronic inflammation and cancer. These biomarkers, according to their
      biologic characteristics are primarily divided into three groups including onco
      foetal protein, stress protein, and post-translational modification. CONCLUSIONS:
      Because of the limitations of traditional HCC biomarkers, exploration for novel
      biomarkers for the diagnosis of HCC is an evolving process.

PMID- 23162602
TI  - Alpha-1-antitrypsin in pathogenesis of hepatocellular carcinoma.
AB  - CONTEXT: Alpha-1-antitrypsin (A1AT) is the most abundant liver-derived, highly
      polymorphic, glycoprotein in plasma. Hereditary deficiency of alpha-1-antitrypsin
      in plasma (A1ATD) is a consequence of accumulation of polymers of A1AT mutants in
      endoplasmic reticulum of hepatocytes and other A1AT-producing cells. One of the
      clinical manifestations of A1ATD is liver disease in childhood and cirrhosis
      and/or hepatocellular carcinoma (HCC) in adulthood. Epidemiology and
      pathophysiology of liver failure in early childhood caused by A1ATD are well
      known, but the association with hepatocellular carcinoma is not clarified. The
      aim of this article is to review different aspects of association between A1AT
      variants and hepatocellular carcinoma, with emphasis on the epidemiology and
      molecular pathogenesis. The significance of A1AT as a biomarker in the diagnosis
      of HCC is also discussed. EVIDENCE ACQUISITIONS: Search for relevant articles
      were performed through Pub Med, HighWire, and Science Direct using the keywords
      "alpha-1-antitrypsin", "liver diseases", "hepatocellular carcinoma", "SERPINA1".
      Articles published until 2011 were reviewed. RESULTS: Epidemiology studies
      revealed that severe A1ATD is a significant risk factor for cirrhosis and HCC
      unrelated to the presence of HBV or HCV infections. However, predisposition to
      HCC in moderate A1ATD is rare, and probably happens in combination with HBV
      and/or HCV infections or other unknown risk factors. It is assumed that
      accumulation of polymers of A1ATD variants in endoplasmic reticulum of
      hepatocytes leads to damage of hepatocytes by gain-of-function mechanism. Also,
      increased level of A1AT was recognized as diagnostic and prognostic marker of
      HCC. CONCLUSIONS: Clarification of a carcinogenic role for A1ATD and
      identification of proinflammatory or some still unknown factors that lead to
      increased susceptibility to HCC associated with A1ATD may contribute to a better
      understanding of hepatic carcinogenesis and to the development of new drugs.

PMID- 23162603
TI  - The role of aflatoxins in hepatocellular carcinoma.
AB  - CONTEXT: Hepatocellular carcinoma (HCC) is one of the most common cancers in the
      world but with a striking geographical variation in incidence; most of the burden
      is in developing countries. This geographic variation in HCC incidence might be
      due to geographic differences in the prevalence of various etiological factors.
      EVIDENCE ACQUISITION: Here, we review the epidemiological evidence linking
      dietary exposure to aflatoxin B1 (AFB1) and risk of HCC, possible interactions
      between AFB1 and hepatitis B virus (HBV) or polymorphisms of genes involved in
      AFB1-related metabolism as well as DNA repair. RESULTS: Ecological, case-control
      and cohort studies that used various measures of aflatoxin exposure including
      dietary questionnaires, food surveys and biomarkers are summarized. CONCLUSIONS:
      Taken together, the data suggest that dietary exposure to aflatoxins is an
      important contributor to the high incidence of HCC in Asia and sub-Saharan
      Africa, where almost 82% of the cases occur.

PMID- 23162604
TI  - The Predictive and Prognostic Significance of c-erb-B2, EGFR, PTEN, mTOR, PI3K,
      p27, and ERCC1 Expression in Hepatocellular Carcinoma.
AB  - BACKGROUND: Hepatocellular carcinoma (HCC) is the fifth most common fatal cancer
      and an important healthcare problem worldwide. There are many studies describing
      the prognostic and predictive effects of epidermal growth factor receptor 2 (c
      erb-B2) and epidermal growth factor receptor 1 (EGFR), transmembrane tyrosine
      kinases that influence cell growth and proliferation in many tumors. OBJECTIVES:
      The current study aimed to investigate the expression levels of c-erb-B2, EGFR,
      PTEN, mTOR, PI3K, p27, and ERCC1 in hepatocellular carcinoma (HCC) and their
      correlation with other clinicopathologic features. PATIENTS AND METHODS: Fifty
      HCC cases were stained immunohistochemically with these markers. Correlations
      between the markers and clinicopathologic characteristics and survival rates were
      analyzed. RESULTS: No membranous c-erb-B2 staining was seen, whereas cytoplasmic
      positivity was present in 92% of HCC samples, membranous EGFR was observed in
      40%, PI3K was found in all samples, and mTOR was seen in 30%, whereas reduced or
      absent PTEN expression was observed in 56% of samples and loss of p27 was seen in
      92% of the cases. c-erb-B2 and mTOR overexpression, as well as reduced expression
      of p27, all correlated with multiple tumors (P = 0.041, P < 0.001, and P < 0.001,
      respectively). P27 loss, and mTOR and EGFR positivity were significantly
      correlated with AFP (P = 0.047, P = 0.004, and P = 0.008, respectively).
      Angiolymphatic invasion was more commonly seen in EGFR- and ERCC1-positive cases
      (P = 0.003 and P = 0.005). EGFR was also correlated with histological grade (P =
      0.039). No significant correlations were found among PTEN , PI3K, and the
      clinicopathological parameters. Disease-free or overall survival rates showed
      significant differences among therapy modalities, AFP levels, angiolymphatic or
      lymph node invasions, and ERCC1 and p27 expression levels (P < 0.05).
      CONCLUSIONS: c-erb-B2, EGFR, mTOR, ERCC1 overexpression levels, and loss of p27
      may play roles in hepatocarcinogenesis and may be significant predictors of
      aggressive tumor behavior. These markers were found to be correlated with certain
      clinicopathologic features, therapy modalities, and survival rates in the current
      study. These findings may help in planning new, targeted treatment strategies .

PMID- 23162605
TI  - Conducting the G-protein Coupled Receptor (GPCR) Signaling Symphony in
      Cardiovascular Diseases: New Therapeutic Approaches.
AB  - G protein-coupled receptors (GPCRs) are a virtually ubiquitous class of membrane
      bound receptors, which functionally couple hormone or neurotransmitter signals to
      physiological responses. Dysregulation of GPCR signaling contributes to the
      pathophysiology of a host of cardiovascular disorders. Pharmacological agents
      targeting GPCRs have been established as therapeutic options for decades.
      Nevertheless, the persistent burden of cardiovascular diseases necessitates
      improved treatments. To that end, exciting drug development efforts have begun to
      focus on novel compounds that discriminately activate particular GPCR signaling
      pathways.

PMID- 23162606
TI  - Beyond Biomarkers: Identifying Cell State using Unbiased Nanosensor Arrays.
AB  - Traditional cell detection based on biomarkers relies on specific lock-and-key
      recognition. However, many diseases either do not have obvious biomarkers or
      these markers are currently unknown. Unbiased sensor arrays based on
      nanoparticles use selective interactions to generate bioprofiles capable of
      identifying cell type and state. As a result, these arrays can differentiate
      subtle variations on the cell surfaces, presenting a potential approach for
      personalized diagnostics.

PMID- 23162607
TI  - TARGETED TREATMENTS IN AUTISM AND FRAGILE X SYNDROME.
AB  - Autism is a neurodevelopmental disorder consisting of a constellation of symptoms
      that sometimes occur as part of a complex disorder characterized by impairments
      in social interaction, communication and behavioral domains. It is a highly
      disabling disorder and there is a need for treatment targeting the core symptoms.
      Although autism is accepted as highly heritable, there is no genetic cure at this
      time. Autism is shown to be linked to several genes and is a feature of some
      complex genetic disorders, including fragile X syndrome (FXS), fragile X
      premutation involvement, tuberous sclerosis and Rett syndrome. The term autism
      spectrum disorders (ASDs) covers autism, Asperger syndrome and pervasive
      developmental disorders (PDD-NOS) and the etiologies are heterogeneous. In recent
      years, targeted treatments have been developed for several disorders that have a
      known specific genetic cause leading to autism. Since there are significant
      molecular and neurobiological overlaps among disorders, targeted treatments
      developed for a specific disorder may be helpful in ASD of unknown etiology.
      Examples of this are two drug classes developed to treat FXS, Arbaclofen, a
      GABA(B) agonist, and mGluR5 antagonists, and both may be helpful in autism
      without FXS. The mGluR5 antagonists are also likely to have a benefit in the
      aging problems of fragile X premutation carriers, the fragile X -associated
      tremor ataxia syndrome (FXTAS) and the Parkinsonism that can occur in aging
      patients with fragile X syndrome. Targeted treatments in FXS which has a well
      known genetic etiology may lead to new targeted treatments in autism.

PMID- 23162609
TI  - Social Networks and the Maintenance of Conformity: Japanese sojourner women.
AB  - Asian immigrant women have the lowest utilization of mental health services of
      any ethnic minority (Garland, Lau, Yeh & McCabe 2005). Because help seeking for
      distress occurs within social networks, we examined how social networks supported
      or disabled help seeking for Japanese sojourners living in the US. Unfortunately,
      most of the literature about Japanese social relationships focuses on men in
      organizational settings. This study used intensive ethnographic interviewing with
      49 Japanese expatriate women to examine how social relationships influenced
      psychosocial distress and help seeking. We found that the women in these samples
      engaged in complex, highly regulated, complicated and obligatory relationships
      through their primary affiliation with other "company wives." Like many immigrant
      women, increased traditional cultural norms (referred to in Japanese as ryoosai
      kenbo, or good wives and wise mothers), were expected from these modern women,
      and the enactment of these roles was enforced through scrutiny, gossip and the
      possibility of ostracism. Fears of scrutiny was described by the women as a
      primary barrier to their self-disclosure and ultimate help seeking. Understanding
      the social organization and support within the Japanese women's community is
      central to understanding how culturally specific social networks can both give
      support, as well as create social constraints to help seeking. Health oriented
      prevention programs must consider these social factors when evaluating the
      immigration stressors faced by these families.

PMID- 23162608
TI  - An intricate dance: Life experience, multisystem resiliency, and rate of telomere
      decline throughout the lifespan.
AB  - Accumulation of life stressors predicts accelerated development and progression
      of diseases of aging. Telomere length, the DNA-based biomarker indicating
      cellular aging, is a mechanism of disease development, and is shortened in a dose
      response fashion by duration and severity of life stressor exposures. Telomere
      length captures the interplay between genetics, life experiences and psychosocial
      and behavioral factors. Over the past several years, psychological stress
      resilience, healthy lifestyle factors, and social connections have been
      associated with longer telomere length and it appears that these factors can
      protect individuals from stress-induced telomere shortening. In the current
      review, we highlight these findings, and illustrate that combining these
      'multisystem resiliency' factors may strengthen our understanding of aging, as
      these powerful factors are often neglected in studies of aging. In naturalistic
      studies, the effects of chronic stress exposure on biological pathways are rarely
      main effects, but rather a complex interplay between adversity and resiliency
      factors. We suggest that chronic stress effects can be best understood by
      directly testing if the deleterious effects of stress on biological aging
      processes, in this case the cell allostasis measure of telomere shortening, are
      mitigated in individuals with high levels of multisystem resiliency. Without
      attending to such interactions, stress effects are often masked and missed.
      Taking account of the cluster of positive buffering factors that operate across
      the lifespan will take us a step further in understanding healthy aging. While
      these ideas are applied to the telomere length literature for illustration, the
      concept of multisystem resiliency might apply to aging broadly, from cellular to
      systemic health.

PMID- 23162610
TI  - Comparative assessment of change in fat mass using dual X-ray absorptiometry and
      air-displacement plethysmography.
AB  - OBJECTIVE: To compare the accuracy of body composition measurements to small,
      defined changes in fat mass between dual X-ray absorptiometry (DXA) and air
      displacement plethysmography (ADP). METHODS: Fifty-six healthy adults, 29 women
      and 27 men (age, 38 +/- 12.4 years; BMI, 27.6 +/- 5.8 kg/m2) were included in the
      study. Exclusion criteria were pregnancy, indwelling metal hardware or
      pacemakers, or weight exceeding DXA table limit (>350 lbs). All individual
      testing was completed within a 2-hour period. Fat packets were prepared using
      lard wrapped in plastic and applied exogenously in defined locations. Each
      participant completed body composition measurements with ADP and DXA (both
      testing modalities completed with and without 1 kg of exogenously applied fat
      mass). RESULTS: Both DXA and ADP were highly accurate in detecting an overall
      increase in body mass associated with exogenously applied 1kg of fat mass (0.99
      kg vs. 0.97 kg, respectively). DXA more accurately detected exogenous fat
      increase as fat mass compared to ADP (0.93 kg; 90% CI for the mean of the
      difference: 0.83 to 1.03 kg vs. 0.45 kg; 90% CI: 0.19 to 0.71 kg, respectively).
      The accuracy of body mass detection was similar for males and females (0.97 vs.
      1.02 for DXA and 0.92 vs. 1.02 for ADP, respectively), though accuracy in
      detecting added mass as fat was less accurate in males than females (0.84 vs.
      1.00 for DXA and 0.39 vs. 0.51 for ADP, respectively). DISCUSSION: Both DXA and
      ADP are accurate in detecting an overall increase in body mass associated with
      exogenously applied 1kg of fat mass. However, DXA is more accurate than ADP in
      correctly identifying the increase in body mass as fat mass, as opposed to fat
      free mass.

PMID- 23162611
TI  - Animal models of extracranial pediatric solid tumors.
AB  - Animal models, including xenografts, models of metastatic invasion, syngeneic
      models and transgenic models, are important tools for basic research in solid
      pediatric tumors, while humanized animal models are useful for novel
      immunotherapeutical approaches. Optical and molecular imaging techniques are used
      for in vivo imaging and may be used in conjunction with alternative treatment
      approaches, including photodynamic therapy. The aim of this review is to
      highlight the various animal models that may be used for basic research in
      pediatric solid tumors.

PMID- 23162612
TI  - Molecular mechanisms of lung-specific toxicity induced by epidermal growth factor
      receptor tyrosine kinase inhibitors.
AB  - Lung-specific toxicity induced by epidermal growth factor receptor (EGFR)
      tyrosine kinase inhibitors (TKIs) for the treatment of non-small cell lung cancer
      (NSCLC) has emerged as a critical side-effect. Although the clinical features of
      the pulmonary side-effects of TKIs have been characterized, the details of the
      molecular mechanisms in the development of this lung-specific toxicity remain to
      be elucidated. EGFR-dependent epithelial regeneration and restoration plays an
      important role in the recovery process from lung injury. The lung comprises a
      unique environment where epithelial cells are exposed to internal agents in the
      systemic circulation and to airborne particles through the mouth and nose. This
      unique environment may also be associated with the development of lung-specific
      toxicity induced by EGFR-TKIs. Therefore, the aim of this review was to provide
      further insight into the molecular mechanisms of lung-specific toxicity in the
      context of treatment with EGFR-TKIs.

PMID- 23162613
TI  - Mitochondrial DNA mutations in human tumor cells.
AB  - Mitochondria play significant roles in cellular energy metabolism, free radical
      generation and apoptosis. The dysfunction of mitochondria is correlated with the
      origin and progression of tumors; thus, mutations in the mitochondrial genome
      that affect mitochondrial function may be one of the causal factors of
      tumorigenesis. Although the role of mitochondrial DNA (mtDNA) mutations in
      carcinogenesis has been investigated extensively by various approaches, the
      conclusions remain controversial to date. This review briefly summarizes the
      recent progress in this field.

PMID- 23162614
TI  - DBC1 does not function as a negative regulator of SIRT1 in liver cancer.
AB  - The putative tumor suppressor, DBC1 (deleted in breast cancer-1), was recently
      found to negatively regulate SIRT1 in vitro and in vivo, but the mechanism
      whereby DBC1 regulates SIRT1 in liver cancer remains to be elucidated. In this
      study, it was found that although the expression of DBC1 and SIRT1 was not
      aberrantly regulated in a large cohort of human hepatocellular carcinoma (HCC)
      patients, these proteins were highly overexpressed in a subset of HCC tissues
      compared with surrounding non-cancer tissues. In liver cancer, DBC1 and SIRT1
      were found to be positively correlated. Inactivation of DBC1 or SIRT1 reduced SNU
      182 (a liver cancer cell line) proliferation as determined by MTT viability
      assays. Notably, although DBC1 functions as a negative regulator of SIRT1 in A549
      lung cancer cells since it suppresses the deacetylase activity of the p53
      protein, it did not affect the p53 deacetylase activity of SIRT1 in SNU-182
      cells. Taken together, we conclude that DBC1 is associated with SIRT1 in HCC, but
      that it does not inhibit SIRT1.

PMID- 23162615
TI  - Fatty acid synthase expression in osteosarcoma and its correlation with pulmonary
      metastasis.
AB  - Previous experimental evidence has suggested that fatty acid synthase (FASN) may
      be involved in cancer metastasis. However, its role has been poorly evaluated in
      osteosarcoma. The aim of this study was to investigate the correlation of FASN
      expression with pulmonary metastasis and the correlation of FASN expression with
      the Ki-67 antigen, a proliferation marker, in patients with osteosarcoma of the
      extremities. The expression of FASN protein and Ki-67 was detected by
      immunohistochemistry of biopsy tissues from 136 patients with osteosarcoma of the
      extremities and 21 cases of osteoenchondroma. Positive expression of the FASN
      protein was observed and located in the cytoplasm. The positive expression rate
      of FASN was 63.2% in osteosarcoma and 28.6% in osteoenchondroma (p<0.05). The
      expression levels of the FASN protein were higher in the cases with lung
      metastasis compared to those without metastasis (p<0.01). The percentage of Ki-67
      stained nuclei in osteosarcoma with pulmonary metastasis and in those without was
      43.43+/-10.05 and 25.41+/-6.68%, respectively (p<0.01). There was a positive
      correlation between FASN and Ki-67 protein expression in osteosarcoma (Spearman's
      rho, F=43.05, R=0.734). Therefore, FASN may be a promising target in the
      treatment of osteosarcoma metastasis.

PMID- 23162616
TI  - Outcomes of palliative bowel surgery for malignant bowel obstruction in patients
      with gynecological malignancy.
AB  - The aim of this study was to evaluate the outcomes of patients with a
      gynecological malignancy who received palliative care with and without surgical
      procedures for malignant bowel obstruction (MBO) and to explore prognostic
      factors to aid the selection of patients who would benefit from palliative
      surgery. Medical records of patients with MBO due to a gynecological malignancy
      treated at our institute between 2005 and 2010 were reviewed. Successful
      palliation following surgery was defined as the ability to tolerate solid food
      for at least 60 days. Clinical variables were analyzed using Chi-square or
      Fisher's exact tests. Survival was evaluated using the Kaplan-Meier method and
      log-rank test. A total of 53 cases were identified; 20 had bowel surgery for MBO
      as a palliative procedure and 33 did not. Colostomy was performed in 11 (55%) of
      20 patients and ileostomy was performed in 7 (35%). The postoperative morbidity
      was 35% and mortality within 30 days was 5%. Successful palliation following
      surgery was achieved in 14 (70%) of 20 cases with a median period of 146 days
      (range, 61-294). Survival following the diagnosis of MBO was longer in cases with
      surgery than those without (median survival time, 146 versus 69 days; P<0.0001).
      Although age, presence of ascites, laboratory values and types of prior
      anticancer therapy were not significantly different, a longer interval from last
      anticancer therapy to diagnosis of MBO was observed in patients who underwent
      surgery compared with those who did not (median, 57 versus 30 days; P<0.05), as
      well as superior performance status. Among the patients with surgery, the
      interval was also longer in patients with successful palliation compared with
      those without (median, 83 versus 32 days; P<0.05). The palliative benefit of
      surgery for MBO in selected patients with gynecological malignancy was observed.
      The interval from last anticancer therapy to diagnosis of MBO may serve as a
      prognostic factor when considering surgical intervention.

PMID- 23162617
TI  - A case of solitary breast metastasis from malignant melanoma of the nasal cavity.
AB  - Metastatic breast tumors are rare; however, malignant melanoma is one of the
      primary tumors most commonly reported to metastasize to the breast. Among these,
      the primary tumors typically associated with metastasis to the breast are
      cutaneous melanomas. We present, herein, a very rare case of solitary metastasis
      to the left breast from malignant melanoma of the nasal cavity, which represents
      less than 1% of all malignant melanomas. The patient, a 78-year-old woman, was
      treated using a combination of surgery and radiotherapy. In the absence of
      therapeutic efficacy, disease progression was very rapid. No previous studies
      have described malignant melanoma of the nasal cavity with solitary breast
      metastasis. This case report aims to increase awareness of the need to establish
      treatment strategies based on an understanding of the etiology and
      pathophysiology.

PMID- 23162618
TI  - Lack of association between expression of MRP2 and early relapse of colorectal
      cancer in patients receiving FOLFOX-4 chemotherapy.
AB  - Recurrence following failure of chemotherapy limits the application of high doses
      of anticancer drugs currently used for eliminating cancerous cells. It has been
      identified that ATP-binding cassette (ABC) multidrug transporters are associated
      with chemoresistance, which is a major obstacle in cancer therapy. The present
      study aimed to investigate the association of pretherapeutic multidrug resistance
      associated protein 2 (MRP2) expression with response to chemotherapy in stage
      II/III colorectal cancer (CRC). Protein expression was determined by
      immunohistochemical analysis of 50 archival samples from patients who had not
      received preoperative chemotherapy and radiotherapy. All patients were treated
      with 5-fluorouracil/leucovorin (FL) plus oxaliplatin (FOLFOX-4) regimen for 6
      months following curative resection. During the 12 months of follow-up, local and
      distant recurrences were observed in 15 (30%) cases, of which 5 occurred at the
      time of chemotherapy. MRP2 expression was observed in 24 (48%) and 7 (14%) cases
      in the tumor tissues and matched normal tissues, respectively. A significant
      difference was observed between the positive expression frequency in the tumor
      tissues compared to the surrounding normal mucosa (P=0.003). The incidence of
      recurrence and metastasis for patients in the MRP2-positive group was lower than
      that in the MRP2-negative group (P>0.05); however, all 5 cases who demonstrated
      recurrence during their treatment were MRP2-positive (P=0.022). MRP2 expression
      was not correlated with the clinicopathological markers in this group of
      patients. Kaplan-Meier analysis revealed that MRP2 expression was not associated
      with a shorter disease-free survival or overall survival of patients (P>0.05).
      The results of this study indicated that MRP2 is overexpressed in the course of
      CRC development and progression. However, expression of MRP2 was not associated
      with recurrence of patients treated with FL and oxaliplatin in the population
      studied.

PMID- 23162619
TI  - Phase I/II study of docetaxel, cisplatin and S-1 in locally advanced, recurrent
      and metastatic head and neck squamous cell carcinoma.
AB  - The purpose of this study was to evaluate the maximum tolerated dose, dose
      limiting toxicities and preliminary efficacy of chemotherapy with cisplatin,
      docetaxel and S-1 (TPS) to treat advanced head and neck squamous cell cancer. S-1
      was administered orally twice daily on days 1-14 and docetaxel and cisplatin were
      injected intravenously on day 8, with one course lasting 4 weeks. The recommended
      dose obtained from a phase I study was set at docetaxel 60 mg/m(2), cisplatin 60
      mg/m(2) and S-1 80 mg/m(2)/day. The phase II study revealed that the overall
      response rate was 81%, comprising 95% in untreated patients with localized
      advanced cancer and no distant metastases, 50% in untreated patients with distant
      metastases and 33% in previously treated patients with recurrence. The overall
      survival rate of untreated patients with localized advanced cancer and no distant
      metastases was 95% at 1 year and 64.33% at 2 years. In terms of grade 3 or higher
      hematotoxicity, neutropenia occurred in 100%, thrombocytotopenia in 4% and anemia
      in 4%. Febrile neutropenia occurred in 46%, with the rate rising to 57% in
      elderly patients >=66 years. Grade 3 or higher non-hematotoxicity consisted of
      loss of appetite in 8%, diarrhea in 8%, hyponatremia in 13% and hypokalemia in
      13%. This TPS therapy may be recommended for use as induction chemotherapy. For
      patients <=65 years, the appropriate dose was docetaxel 60 mg/m(2), cisplatin 60
      mg/m(2) and S-1 80 mg/m(2), whereas for those >=66 years, it was docetaxel 60
      mg/m(2), cisplatin 60 mg/m(2) and S-1 60 mg/m(2).

PMID- 23162620
TI  - Outcome in disappearing colorectal cancer liver metastases during oxaliplatin
      based chemotherapy.
AB  - Some colorectal cancer liver metastases (CLMs) disappear on serial imaging during
      chemotherapy and the optimal treatment strategy for such lesions remains
      undetermined. The purpose of this study was to investigate the outcome in
      disappearing CLMs, as few studies have focused on this topic, with conflicting
      results. Among 125 patients with CLMs treated with modified FOLFOX6 with or
      without bevacizumab, those in whom all CLMs disappeared on computed tomography
      were identified. Recurrence of such disappearing lesions in situ was examined on
      a tumor-by-tumor basis. Five (4%) patients with a total of 44 CLMs met the
      evaluation criteria. The median number of CLMs prior to chemotherapy was 8
      (range, 2-16). The median maximal diameter of the CLMs was 1.8 cm (range, 1.0
      2.4). The median time-to-disappearance of all eligible lesions was 6.5 months
      (range, 4.5-7.5). Histological examination of scar lesions on the liver surface
      revealed no viable cancer cells. Two lesions were surgically resected. During
      clinical follow-up of the remaining 42 lesions, in situ recurrence was observed
      in 8. The cumulative 1-, 2- and 3-year rates of relapse in situ were 9.1, 9.1 and
      31.1%, respectively. Given the low risk of recurrence in situ, the results
      suggest that the sites of disappearing CLMs may be left unresected but should be
      carefully monitored during follow-up, with resection an option if the lesion
      should recur. However, to validate such a treatment strategy, further
      investigation with a larger series of patients is warranted.

PMID- 23162621
TI  - Clinicopathological characteristics of rectal carcinoid patients undergoing
      surgical resection.
AB  - The aim of this study was to clarify the clinical aspects, histopathological
      features and prognosis of patients with rectal carcinoids, focusing on properties
      associated with metastasis, in order to gain insights into appropriate
      management. A total of 20 patients (15 males, 5 females; mean age, 54.9 years;
      range, 23-71) who underwent surgery for rectal carcinoid tumors at the Department
      of Colorectal Surgery, Hyogo College of Medicine, between May 2000 and January
      2011 were analyzed. Ki-67 immunostaining was performed in 13 cases with available
      tumor tissue specimens. Of the 20 patients, a radical operation including rectal
      resection with a lymphadenectomy was performed in 16. The mean tumor size was
      11.9 mm (3-25 mm) and lymph node metastasis was confirmed in 9 cases, including 3
      with lesions no greater than 7 mm in diameter. Overall, 16 (80%) of the tumors
      were localized in the submucosal layer and 4 (20%) involved the proper muscle
      layer. Ki-67 labeling index and lymphovascular invasion were shown to be
      associated with lymph node and/or distant metastasis by multiple logistic
      regression analysis, but were not statistically significant in ANOVA findings.
      Lymph node metastasis from rectal carcinoids, even those smaller than 10 mm in
      diameter, was not a rare event. More attention should be given to decision
      making, including the possibility of endoscopic resection for the treatment of
      rectal carcinoid tumors regardless of size.

PMID- 23162622
TI  - Colonic explosion during treatment of radiotherapy complications in prostatic
      cancer.
AB  - The use of lasers has been of great importance in the field of endoscopy and
      surgery for their applications in coagulation and the ability to vaporize tissue.
      In the 1990s, new machines were introduced based on a different technology, the
      argon-plasma-coagulation (APC) system. This technology causes different
      biological effects without direct contact. An example is the hemostasis of
      bleeding. In the literature, several cases of complications have been reported
      during endoscopic treatment with APC. In this study, we report our experience of
      a case with colon explosion during an APC procedure for bleeding due to
      radiotherapy and also review the literature on the complications of APC
      treatment.

PMID- 23162623
TI  - Regulation of neutrophil gelatinase-associated lipocalin expression by C/EBPbeta
      in lung carcinoma cells.
AB  - Neutrophil gelatinase-associated lipocalin (NGAL), a member of the lipocalin
      family, has been found to be overexpressed in a variety of tumors, including lung
      adenocarcinomas. However, the mechanism by which NGAL expression is regulated in
      lung carcinoma needs further evaluation. In this study, immunohistochemistry was
      employed to analyze the expression of NGAL in lung carcinoma tissue samples,
      including lung squamous carcinomas, adenocarcinomas, adenosquamous carcinomas and
      bronchial alveolar cell carcinomas. The results showed that NGAL was expressed in
      82.61% (19/23) of the samples. RT-PCR and immunofluorescent staining showed that
      NGAL was localized to the cytoplasm in lung carcinoma cell lines. To explore the
      transcriptional regulation mechanism of NGAL basal expression in lung carcinoma,
      a 1515-bp fragment (-1431 to +84) of the NGAL promoter region was cloned and a
      series of deletion and mutation constructs were generated. These constructs were
      analyzed using the luciferase reporter assay. The results indicated that the cis
      acting elements important for the basal activity of NGAL transcription were
      likely located between -152 and -141. Further analysis using site-directed
      mutagenesis and the luciferase reporter assay suggested that the C/EBP binding
      sites were responsible for the activity of the NGAL promoter. Finally, the
      binding ability and specificity of the transcription factors were determined by
      electrophoretic mobility-shift assay (EMSA). The results showed that C/EBPbeta
      was able to bind to the -152 and -141 segments. Taken together, these findings
      suggest that NGAL is expressed in lung carcinomas and that NGAL expression is
      mediated by the binding of C/EBPbeta to the -152 and -141 segment of the NGAL
      promoter.

PMID- 23162624
TI  - Expression of UDP-glucuronosyltransferase 1A, nuclear factor erythroid-E2-related
      factor 2 and Kelch-like ECH-associated protein 1 in colonic mucosa, adenoma and
      adenocarcinoma tissue.
AB  - We investigated the expression of UDP-glucuronosyltransferase 1A (UGT1A), nuclear
      factor erythroid-E2-related factor 2 (Nrf2) and Kelch-like ECH-associated protein
      1 (Keap1) in normal colonic mucosa, adenoma tissue and adenocarcinoma tissue, to
      analyze the correlation between their expression and the clinicopathological
      features of adenocarcinoma and their roles in colonic carcinogenesis. Using
      immunohistochemical analysis, we investigated the expression of UGT1A, Nrf2 and
      Keap1 in normal colonic mucosa (n=24), adenoma tissue (n=30) and adenocarcinoma
      tissue (n=77). We found that the positive rate of UGT1A was 83.3% in normal
      colonic mucosa, 80.0% in adenoma tissue and significantly lower, 53.2%, in
      adenocarcinoma tissue (normal colonic vs. adenoma tissue, P=0.071; normal colonic
      vs. adenocarcinoma tissue, P=0.023; adenoma vs. adenocarcinoma tissue, P=0.019).
      The expression levels of Nrf2 were high in adenoma and adenocarcinoma tissues,
      with positive rates of 70.0 and 87.0%, respectively, but were significantly lower
      in normal colonic tissue, with a positive rate of 41.7% (normal colonic vs.
      adenoma tissue, P=0.000; normal colonic vs. adenocarcinoma tissue, P=0.000;
      adenoma vs. adenocarcinoma tissue, P=0.000). The positive rate of Keap1 was 54.2%
      in normal mucosa, 70.0% in adenoma tissue and 61.0% in adenocarcinoma tissue
      (normal colonic mucosa vs. adenoma tissue, P=0.200; normal colonic vs.
      adenocarcinoma tissue, P=0.040; adenoma vs. adenocarcinoma, P=0.002). In
      addition, there was no correlation between the expression of Nrf2/Keap1 in
      adenoma and adenocarcinoma tissues (r=0.067, P=0.723; r=0.042, P=0.715,
      respectively). The results suggest that decreased expression of UGT1A and the
      dysregulation of the Nrf2/Keap1 system may be related to colonic carcinogenesis.

PMID- 23162625
TI  - A case of multiple primary malignancies and investigation of family history.
AB  - The occurrence of multiple primary malignancies (MPM) in one patient is a rare
      but increasingly frequent event, partly due to medical advances in diagnosis and
      therapy. A number of theories have been proposed to explain MPM, but none have
      been proven. A key risk factor appears to be family history. We present the case
      of a 43-year-old male with multiple cancers who was first admitted to the
      hospital for an undifferentiated pleomorphic sarcoma/pleomorphic malignant
      fibrous histiocytoma (pG2T2bN0Mx stage III) of the right scapula in May 2009. The
      patient underwent three tumor resections in situ due to tumor recurrence. During
      the period of chemotherapy and radiotherapy, computed tomography (CT) revealed a
      10x10-cm enhancing soft mass of the ascending colon, which was diagnosed as
      mucinous adenocarcinoma in a pathological report. Laboratory data showed elevated
      serum levels of carcinoembryonic antigen (CEA, 20.0 MUg/l; normal range, 0.0-10.0
      MUg/l). Certain family members of the patient had been diagnosed with
      endometrial, colon and pancreatic cancer. None of the family had a smoking
      history or presented with familial adenomatous polyposis (FAP). The patient with
      hereditary non-polyposis colorectal cancer (HNPCC), whose family fulfilled
      Amsterdam Criteria I (AC I), has remained free of disease for 15 months. Family
      history may be a key risk factor for MPM and HNPCC, the detailed molecular
      mechanisms of which remain to be elucidated. This case report with an
      investigation of family history may improve the clinical recognition of HNPCC and
      MPM.

PMID- 23162626
TI  - Detection of single tumor cell resistance with aptamer biochip.
AB  - In this study, a novel RNA aptamer biochip was developed for tumor cell capture
      and detection of single cell resistance. This biochip consists of a
      polydimethylsiloxane (PDMS) cover containing a channel for introducing cells and
      sustaining their activity and microelectrode matrix on a silicon dioxide layer.
      Epidermal growth factor receptor (EGFR) aptamers which specifically identify and
      isolate tumor cells were attached in the gap between two electrodes. After cell
      biochip incubation, surplus tumor cells were removed, and those dwelling on the
      intervals were further analyzed. When resistance measurement was completed, these
      cells were flushed away via controlled flow acceleration, and were collected for
      further analysis. The results demonstrate the convenience and efficiency of using
      anti-EGFR aptamer biochips for the detection of single cell resistance. This
      novel aptamer biochip may be used for the isolation of circulating tumor cells
      from peripheral blood and cell counting, or be assembled with other lab-on-a-chip
      components for follow-up gene and protein analysis.

PMID- 23162628
TI  - Hepatoid carcinoma of the ovary: A case report and review of the literature.
AB  - Hepatoid carcinoma of the ovary is a type of tumor resembling hepatocellular
      carcinoma that arises from the ovary. Hepatoid carcinoma patients are
      predominantly elderly females ranging between 35 and 78 years of age, with an
      average age of 56 years. It was suggested that, microscopically, bile canalicular
      structures are rare, but among nine cases examined for bile canalicular
      structures, four demonstrated a positive result. Here, we report a case of a 55
      year-old female who presented to the Second Xiangya Hospital, Changsha, China,
      with lower abdominal pain, abdominal distention and increasing abdominal girth.
      The patient underwent total hysterectomy, bilateral salpingo-oophorectomy,
      omentectomy, tumor debulking and postoperative chemotherapy. A mass in the left
      ovary measuring approximately 11 cm in diameter was identified. Microscopic and
      immunohistochemical results suggested that it was a hepatoid carcinoma of the
      left ovary.

PMID- 23162627
TI  - Let-7b and microRNA-199a inhibit the proliferation of B16F10 melanoma cells.
AB  - Cutaneous melanoma is an aggressive form of human skin cancer characterized by
      high metastatic potential and poor prognosis. Biomarkers of metastatic risk are
      critically needed to instigate new auxiliary measures in high-risk patients. In
      clinical specimens of skin melanoma, we previously found that let-7b, microRNA
      199a and microRNA-33 were significantly associated with metastatic melanoma, and
      thus may be the key to melanoma treatment. In this study, we examined the effect
      of overexpression and inhibition of let-7b and microRNA-199a. Plasmids
      overexpressing these genes were transfected into B16F10 melanoma cells, and let
      7b and microRNA-199a expression were evaluated at the RNA, protein and cellular
      level. Cyclin D1 expression was significantly higher in cells transfected with
      let-7b plasmid and let-7b inhibitor compared with control cells (P<0.05). In
      turn, Met expression in the microRNA-199a plasmid group and microRNA-199a
      inhibitor group was significantly higher than in the control group (P<0.05). The
      proliferation rate of B16F10 cells transfected with let-7b or microRNA-199a was
      lower than that of the control group, particularly until the third day after
      transfection when the proliferation rate dropped to the lowest value (P<0.05). In
      addition, the apoptosis rates of the let-7b plasmid group and microRNA-199a
      plasmid group were significantly higher compared to that of the control group
      (P<0.05). These results suggest that let-7b and microRNA-199a may be negative
      regulators of B16F10 cell proliferation.

PMID- 23162629
TI  - Management of primary adenocarcinoma of the female urethra: Report of two cases
      and review of the literature.
AB  - Primary adenocarcinoma of the female urethra is rare and only a few retrospective
      cases have been published. The origin of urethral adenocarcinomas remains
      unclear. Certain authors have suggested that urethral adenocarcinomas in females
      originate at the periurethral Skene's glands. We report one case of urethral
      adenocarcinoma of the proximal urethra in a 44-year-old female who presented with
      painless urethral bleeding. Abdominal and pelvic CT scan with contrast and chest
      radiology were unremarkable. Biopsy of the mass revealed adenocarcinoma of the
      urethra. The patient was treated with partial urethrectomy and was free of
      disease for more than 5 years. We also present another rare case of mucinous
      adenocarcinoma in a 52-year-old female who complained of an enlarged urethral
      mass. Pelvic MRI revealed a tumor surrounding the whole urethra and bilateral
      inguinal lymph nodes. A puncture biopsy later revealed that the tumor was
      mucinous adenocarcinoma. Anterior pelvic exenteration with pelvic and bilateral
      lymph node dissection was performed and chemotherapy was administered. The
      patient was followed up for 12 months and did not experience local recurrence or
      distant metastasis. In conclusion, for the diagnosis of urethral cancer, a biopsy
      is necessary for any suspicious urethral lesions. MRI is recommended for tumor
      staging. Small, superficial, distal urethral tumors may be treated with excision
      of the distal urethra. For advanced female urethral cancer, a combination of
      chemotherapy, radiation therapy and surgery is recommended for optimal local and
      distant disease control. Regular follow-up is required in these patients.

PMID- 23162630
TI  - Synovial sarcoma arising in the vulva cytogenetically confirmed by SYT break
      apart rearrangement fluorescence in situ hybridization: A case report and
      discussion of diagnostic methods.
AB  - Synovial sarcoma (SS) is a soft tissue sarcoma of unknown histogenesis that
      rarely occurs in the female genital tract. We report a case of SS occurring in
      the right vulva of a young Japanese female. The tumor was composed of poorly
      differentiated rounded cell areas, surrounded by fibroblastic spindle-shaped cell
      areas. Immunohistochemically, the tumor cells were focally positive for
      cytokeratin, vimentin, CD99, Bcl-2 and neuron-specific enolase. The tumor was
      suspected, but was difficult to confirm as it was an SS based solely on light
      microscopic and immunohistochemical findings. Although reverse transcription
      polymerase chain reaction (RT-PCR) failed to detect SS-specific SYT-SSX fusion
      gene transcripts using an RNA sample extracted from the formalin-fixed paraffin
      embedded tumor tissue, SYT break-apart rearrangement fluorescence in situ
      hybridization (SYT bar-FISH) successfully confirmed our diagnosis of SS for the
      tumor. Thus, SYT bar-FISH may be more suitable for the purpose of the molecular
      diagnosis of SS than conventional RT-PCR when using archival formalin-fixed
      paraffin-embedded tissue specimens.

PMID- 23162631
TI  - Expression of the adipocytokine resistin and its association with the
      clinicopathological features and prognosis of pancreatic ductal adenocarcinoma.
AB  - Fat tissue is viewed as an active endocrine organ that secretes a variety of
      bioactive substances. Resistin, an adipocyte-secreted factor, is thought to be
      closely related to obesity, insulin resistance and inflammation, the three most
      significant risk factors for the progression of pancreatic cancer. However, the
      association between resistin and pancreatic cancer is still unknown. In this
      study, pancreatic tumor samples from 45 patients with pancreatic ductal
      adenocarcinoma were analyzed with immunohistochemistry for the expression of
      resistin. The correlation between resistin expression and clinicopathological
      features and prognosis were evaluated. Resistin staining was observed in 48.9%
      (22 of 45) of the cases. Resistin expression was more frequent in poorly
      differentiated tumors (9 of 9, 100%) compared to moderately differentiated tumors
      (11 of 28, 39.3%) and well-differentiated tumors (2 of 8, 25%) (p<0.01). The
      incidence of resistin expression in patients with Japan Pancreas Society stages
      III-IV (18 of 27, 66.7%) was significantly higher than in subjects with stages I
      II (4 of 18, 22.2%) (p<0.01). Patients with resistin-stained tumors had
      significantly shorter relapse-free survival times (median, 9 months) than
      patients with negative tumors (median, 18 months) (p<0.05). In addition,
      multivariate analysis showed that resistin expression was an independent
      prognostic factor for relapse-free survival of patients with pancreatic ductal
      adenocarcinoma (p<0.05). These results demonstrate that resistin may influence
      the progression of pancreatic tumors and may be a useful predictor of relapse
      free survival in patients with pancreatic ductal adenocarcinoma.

PMID- 23162632
TI  - Intra- and postoperative complications in 137 cases of giant thyroid gland tumor.
AB  - The intra- and postoperative complications resulting from surgery for giant
      thyroid gland tumors (diameter greater than 10 cm) present serious challenges to
      patient recovery. Although there are a number of methods, all have limitations.
      In this study, we present our experience with several complications of surgical
      treatment of giant thyroid gland tumors to increase the awareness and aid the
      prevention of these complications. A total of 137 consecutive patients who
      underwent surgical treatment in Henan Tumor Hospital were retrospectively
      analyzed. Statistics pertaining to the patients' clinical factors were gathered.
      We found that the most common surgical complications were recurrent laryngeal
      nerve (RLN) injury and symptomatic hypoparathyroidism. Other complications
      included incision site infections, bleeding, infection and chyle fistula, the
      incidence of which increased significantly with increasing extent of surgery from
      group I (near-total thyroidectomy) to group V (total thyroidectomy plus lateral
      neck dissection). Low complication rates may be achieved with more accurate
      knowledge of the surgical anatomy, skilled surgical treatment and experience.
      More extensive surgery results in a greater number of complications.

PMID- 23162633
TI  - Ultrasound microbubble contrast agent-mediated suicide gene transfection in the
      treatment of hepatic cancer.
AB  - The aim of this study was to investigate the role of ultrasound microbubble
      contrast agent-mediated suicide gene transfection in the treatment of hepatic
      cancer. We intratumorally injected KDR-TK, AFP-TK and microbubble contrast agent
      into nude mice prior to ultrasound treatment and administration of prodrugs (GCV
      and 5-FC). The tumor volume, tumor inhibition rate, survival time and apoptosis
      of tumor cells was determined. The sizes of subcutaneous hepatic cancers in mice
      receiving treatment were comparable to those in the control group, and the
      survival time was similar between the two groups (P>0.05). However, the tumor
      inhibition rate and the number of apoptotic cells in the treatment group was
      markedly higher compared with that in the control group (P<0.05). Evident tumor
      necrosis was absent in both groups, except at the needle tract. Ultrasound
      therapy following injection of suicide genes and microbubble contrast agents is
      able to inhibit cancer growth in vivo. This may be attributed to the induction of
      cancer cell apoptosis.

PMID- 23162634
TI  - Fusion PET-CT detection of neurolymphomatosis originating from primary breast
      lymphoma: A case report and literature review.
AB  - Neurolymphomatosis (NL) is an extremely rare manifestation. Involvement of the
      cranial and peripheral nerves is an unusual manifestation of NL which is
      occasionally difficult to diagnose using conventional imaging modalities. A 45
      year-old female in complete remission from primary breast lymphoma presented with
      multiple neurological symptoms. (18)F-FDG PET/CT revealed multiple nodular
      hypermetabolic lesions along the cranial and peripheral nerves, which
      corresponded to the patient's neurological symptoms. These findings suggest that
      (18)F-FDG PET/CT successfully detects the infiltration of cranial and peripheral
      nerves by lymphoma.

PMID- 23162635
TI  - Antitumor activity of Endostar combined with radiation against human
      nasopharyngeal carcinoma in mouse xenograft models.
AB  - Radiation treatment for nasopharyngeal carcinoma (NPC) is common and effective.
      However, local recurrence occurs frequently. Endostar, a novel recombinant human
      endostatin, is an antiangiogenic drug with a potent antitumor effect. The present
      study aimed to observe and explore the radiosensitization effects of Endostar on
      NPC and its underlying mechanism. The NPC subcutaneous transplantation tumor
      animal model was established to evaluate the antitumor activity of Endostar
      combined with radiation (Endostar + radiation) treatment compared with
      monotherapy (Endostar or radiation). Tumor growth and tumor weight were measured
      to evaluate the antitumor effect. The level of vascular endothelial growth factor
      (VEGF) and microvessel density (MVD) were measured using immunohistochemical
      staining of the tumor tissues. Significant antitumor activity was found in the
      Endostar + radiation group. The tumor inhibition rates of Endostar, radiation and
      Endostar + radiation were 27.12, 60.45 and 86.11%, respectively. The VEGF levels
      in the tumor tissue in the Endostar + radiation group were lower than those in
      the radiation and control groups. The MVD in the tumor tissues in the Endostar +
      radiation group was 12.2+/-2.5, lower than that in the Endostar (29.3+/-3.4),
      radiation (23.5+/-3.6) and control (44.7+/-5.1) groups. These results suggest
      that Endostar increases the radiation sensitivity of NPC-transplanted tumors in
      nude mice by lowering VEGF expression. In this study, the NPC animal model was
      established, which reflects the efficacy of clinical combination therapies and
      the combination of Endostar and radiation. The mechanisms of the combination
      therapies should be further investigated using this model.

PMID- 23162636
TI  - The role of the TOB1 gene in growth suppression of hepatocellular carcinoma.
AB  - The TOB1 gene, mapped on 17q21, is a member of the BTG/Tob family. In breast
      cancer it has been identified as a candidate tumor suppressor gene. However,
      whether TOB1 is a bona fide tumor suppressor and downregulated in hepatocellular
      carcinoma (HCC) remains unclear. In addition, whether its expression is regulated
      through methylation requires investigation. In the present study, we therefore
      analyzed the expression of TOB1 in HCC and its methylation levels in human HCC
      and breast cancer. No significant difference in the expression levels of TOB1 was
      observed between tumor tissues and adjacent normal tissues in HCC. Quantitative
      methylation analysis by MassArray revealed no significant differences at single
      CpG sites or in the global promoter region, and all these CpG sites shared a
      similar methylation pattern in HCC and breast cancer. Moreover, 5-aza-2'
      deoxycytidine treatment of three tumor cell lines did not cause elevation of TOB1
      mRNA in HepG2 cell lines. Based on these data, we speculate that TOB1 may be a
      candidate non-tumor suppressor gene in HCC. Furthermore, the clinical outcome was
      not correlated with TOB1 expression or expression rate. In addition, TOB1
      expression or expression rate was not correlated with the overall survival (OS)
      rates or cumulative recurrence rates. Taken together, we suggest that TOB1 does
      not act as a tumor suppressor in HCC.

PMID- 23162637
TI  - Expression of deleted in liver cancer 2 in colorectal cancer and its correlation
      with clinicopathological parameters.
AB  - Deleted in liver cancer 2 (DLC2) has been identified as a tumor suppressor gene.
      DLC2 is closely related to deleted in liver cancer 1 (DLC1) and is located at
      chromosome 13q12.3. The expression of DLC2 mRNA has been found in a wide range of
      cancers, including colorectal cancer (CRC). However, there are no available data
      on the expression status of DLC2 in Chinese patients with CRC and its correlation
      with clinicopathological parameters. The aim of this study was to investigate the
      expression levels of DLC2 mRNA and protein in Chinese patients with CRC and the
      correlation between DLC2 expression and clinicopathological parameters. To this
      end, real-time PCR, western blotting and immunohistochemistry were employed to
      detect DLC2 mRNA and protein expression in CRC and pericarcinomatous intestinal
      tissue (PCIT) specimens, which were obtained from 102 Chinese CRC patients who
      underwent surgical resection between October 2010 and February 2012. We also
      analyzed the correlations between DLC2 expression and the clinicopathological
      parameters of CRC patients. Our results showed that CRC tissues had significantly
      lower levels of DLC2 mRNA compared with PCITs (P<0.05); however, the protein
      expression levels were not significantly different between CRCs and PCITs. The
      expression levels of DLC2 mRNA and protein were significantly correlated with
      lymph node metastasis and tumor TNM stage. Additionally, DLC2 mRNA expression
      levels were also correlated with tumor histopathological degree (P<0.05).
      Collectively, our results suggest that the downregulated expression of DLC2
      participates in CRC carcinogenesis, invasion and lymph node metastasis.
      Furthermore, our results imply that DLC2 is be a potential prognostic marker for
      CRC patients.

PMID- 23162638
TI  - Two malignant solitary fibrous tumors in one kidney: Case report and review of
      the literature.
AB  - Malignant solitary fibrous tumors of the kidney are very rare. Two tumors in one
      kidney is particularly rare and has not been previously reported. Due to the non
      specific clinical symptoms, it is difficult but also very significant to give a
      definite diagnosis. Here, we report a case of two renal masses in one kidney. A
      56-year-old man was admitted to our hospital complaining of shortness of breath,
      weakness, hyperhidrosis and intermittent hypoglycemia of 1-year duration without
      gross hematuria or lumbago. Imaging studies revealed two masses manifesting as
      inhomogeneous, with soft-tissue density and having no clear boundaries with the
      kidney. The patient was initially diagnosed with space-occupying lesions of the
      left kidney (with suspicions of renal cell carcinoma) and left radical
      nephrectomy was performed. Histologically, the tumors consisted of ovoid or
      spindle cells, and a hemangiopericytoma-like pattern and cellular atypia was
      observed in certain areas. Mitotic figures were more than 4 per 10 high-power
      fields. Immunohistochemically the tumor cells were positive for CD34, CD99 and
      vimentin. Accordingly, a diagnosis of malignant solitary fibrous tumor of the
      left kidney (low-grade malignance) was established. Postoperative follow-up of 10
      months did not find tumor recurrence or metastasis and hypoglycemia was resolved
      with the removal of the tumors.

PMID- 23162639
TI  - In vitro gastric cancer cell imaging using near-infrared quantum dot-conjugated
      CC49.
AB  - In this experiment, we developed a bioprobe label for immunofluorescence using
      gastric tumor-specific quantum dots (QDs) to detect gastric tumor cells in vitro.
      The fluorescent probe, which is capable of specifically labeling gastric tumor
      cells, was constructed by taking advantage of the unique and superior properties
      of QDs. We grafted primary QDs onto the tumor-associated glycoprotein 72 (TAG-72)
      monoclonal antibody CC49 to produce CC49-QDs that specifically label tumor cells.
      Following a series of tests on the diameter and emission spectrum of CC49-QDs,
      they were employed in immunofluorescence analysis. Transmission electron
      microscopy and fluorescence spectrum analyses indicated that CC49-QDs had a 0.25
      nm higher average diameter than the primary QDs, and that the grafted CC49 had no
      difference in optical properties compared to the primary QDs. In cell imaging,
      the cells labeled with CC49-QDs generated brighter fluorescence compared with the
      cells of the primary QD group. The results of immunofluorescence analysis
      demonstrated that antibody grafting reinforced the specific binding of QDs to
      tumor cells. This probe may also be further applied to live gastric cancer animal
      models to track lymphatic metastasis. In addition, it may potentially offer
      theoretical support for lymphadenectomy in the treatment of gastric cancer.

PMID- 23162640
TI  - Expression of connexin 32 and connexin 43 in acute myeloid leukemia and their
      roles in proliferation.
AB  - Connexins (Cxs), a conserved family of trans-membrane proteins, function in the
      organization of cell-cell communicatin via gap junctions in multicellular
      organisms. However, the role of Cxs in acute myeloid leukemia (AML) is poorly
      understood. In this study, we investigated the relationship between cell
      proliferation and expression of connexin 43 (Cx43) and connexin 32 (Cx32) mRNA
      and proteins in acute myeloid leukemia in vitro. Proliferation was observed using
      a growth curve and the rate of proliferation was detected by MTT assay in the
      acute myeloid leukemia cell lines OCI-AML3 and OCIM2. Cell cycle and cell
      proliferation index were assessed by flow cytometry analysis. The mRNA expression
      of the gap junction genes Cx43 and Cx32 was detected by RT-PCR. The expression of
      Cx43 and Cx32 proteins in the cell lines was analyzed by western blot analysis
      and immunofluorescence. The doubling time of OCI-AML3 and OCIM2 was 48 h and 36
      h, respectively. In OCIM2, the percentage of cells in the S phase fraction was
      59.47+/-9.6%, and the proliferation rate was 78.12+/-8.9%; however, in OCI-AML3,
      the percentage of cells in the S phase was 24.95+/-5.8%, and the proliferation
      rate was 35.21+/-6.7%. At the mRNA level, both cell lines expressed Cx43 and
      Cx32, and there was no significant difference in the expression of Cx43 and Cx32
      mRNA in the two cell lines. At the protein level, there was a significant
      difference in the expression of Cx43, but not of Cx32. The proliferation ability
      of OCIM2 was higher than OCI-AML3, and OCIM2 exhibited higher Cx43 western blot
      and fluorescence intensities compared with OCI-AML3. The results suggest that a
      higher expression of Cx43 in AML cells may play a significant role in the
      proliferation ability.

PMID- 23162641
TI  - Biomarker expression in normal fimbriae: Comparison of high- and low-grade serous
      ovarian carcinoma.
AB  - The objective of this study was to assess the difference in fimbriae of high- and
      low-grade ovarian serous carcinoma (OSC). The fimbriae of normal appearance
      [without serous tubal intraepithelial carcinoma (STIC)] from 28 patients with
      high-grade OSCs and 24 patients with low-grade OSCs were assessed for the
      expression of 6 markers [E-cadherin, matrix metalloproteinase-2 (MMP-2), phospho
      AKT (pAKT), cyclooxygenase-2 (COX-2), vascular endothelial growth factor (VEGF)
      and p53] using immunohistochemistry. Sectioning and extensively examining the
      fimbria (SEE-FIM) was performed to exclude fimbrial involvement for all the
      cases. The immunostaining levels of pAKT and COX-2 were significantly higher in
      the fimbriae of normal appearance from high-grade OSCs compared with low-grade
      OSCs (61 vs. 8% and 71 vs. 21%; P=0.005 and 0.007, respectively). The
      immunostaining of E-cadherin was significantly higher in the fimbriae of low
      grade OSCs compared with high-grade OSCs (83 vs. 21%; P= 0.003). The remaining 3
      markers (MMP-2, VEGF and p53) had similar expression in low- and high-grade OSCs
      (21 vs. 13%; 25 vs. 21%; and 14 vs. 8%; P=0.78, 0.86 and 0.82, respectively). Our
      results suggest marked biological differences in the behavior of the fimbriae in
      high- and low-grade OSCs and indicate that proliferation, cell adhesion and the
      inflammatory microenvironment of fimbriae in high-grade OSCs without STIC had
      changed prior to p53 mutation.

PMID- 23162642
TI  - Two consecutive days of treatment with liposomal cisplatin in non-small cell lung
      cancer.
AB  - Liposomal cisplatin (Lipoplatin) is a new agent, a cisplatin formulation that has
      been investigated in a number of studies and compared with cisplatin with respect
      to toxicity and effectiveness. It has been administered once weekly and in
      combination with a second agent, once every two weeks. The main outcome of the
      studies was that lipoplatin has no renal toxicity and is as equally effective as
      cisplatin. The present study investigated toxicity and effectiveness when
      lipoplatin is administered on two consecutive days, repeated every two weeks.
      Between January 2011 and November 2011, a total of 21 patients with
      histologically- or cytologically-confirmed non-small cell lung cancer (NSCLC)
      were enrolled in the study. All but two patients, who had not been pretreated,
      had received one or two series of chemotherapy and some had undergone
      radiotherapy. Lipoplatin monotherapy was infused for 8 h the first and second
      days and repeated every 2 weeks with the aim of administering 6 cycles. The dose
      per day was 200 mg/m(2). Eight out of 21 (38.10%) patients had a partial
      response, 9 (42.86%) had stable disease and 4 (19.05%) had progressive disease.
      Results showed that there was no renal failure toxicity and no other adverse
      reactions apart from grade 1 myelotoxicity in only 2 patients who had been
      heavily pretreated, and grade 1 nausea/vomiting in 4 patients. Liposomal
      cisplatin is an agent with negligible toxicity and reasonably high effectiveness
      even when administered to pretreated patients with NSCLC.

PMID- 23162643
TI  - Nedaplatin and irinotecan combination therapy is equally effective and less toxic
      than cisplatin and irinotecan for patients with primary clear cell adenocarcinoma
      of the ovary and recurrent ovarian carcinoma.
AB  - This study retrospectively compared nedaplatin and irinotecan hydrochloride
      (NDP/CPT) combination therapy with cisplatin and irinotecan hydrochloride therapy
      (CDDP/CPT) for efficacy and adverse events in the treatment of clear cell
      adenocarcinoma of the ovary (CCC) and recurrent ovarian carcinoma. A total of 115
      patients were included in the present study. NDP/CPT was administered
      intravenously every 4 weeks (NDP, 60 mg/m(2) on day 1; CPT, 50 mg/m(2) on days 1,
      8 and 15). CDDP/CPT was also administered intravenously (CDDP, 60 mg/m(2) on day
      1; CPT, 60 mg/m(2) on days 1, 8 and 15). Patients with primary CCC were treated
      with NDP/CPT in 29 cases and CDDP/CPT in 20 cases. Patients with recurrent
      ovarian carcinoma were treated with NDP/CPT and CDDP/CPT in 33 cases each. No
      significant difference was observed in the 5-year overall survival
      (OS)/progression-free survival (PFS) of patients with primary CCC, with the
      exception of those patients with stages Ia and Ic(b) who underwent NDP/CPT and
      CDDP/CPT treatments (OS: 58%, PFS: 40% and OS: 53% and PFS: 47%, respectively).
      No significant differences were found in the response rates to NDP/CPT and
      CDDP/CPT in patients with recurrent ovarian carcinoma (27 and 18%, respectively).
      Similarly, there were no significant differences in the 5-year OS and PFS of
      patients with recurrent ovarian carcinoma treated with NDP/CPT or CDDP/CPT (OS:
      15%, PFS: 3% and OS: 18%, PFS: 6%, respectively). In terms of the hematological
      toxicity of grade 3 or above and non-hematological toxicity of grade 2 or above
      in patients treated with NDP/CPT and CDDP/CPT, respectively, neutropenia was 23
      and 56%; anemia, 1, and 20%; thrombocytopenia, 0 and 5%; nausea, 20 and 52%;
      diarrhea, 14 and 25%; and fever, 2 and 11%. Accordingly, NDP/CPT indicated mild
      toxicity, and was therefore equally effective and less toxic than CDDP/CPT in the
      treatment of primary CCC and recurrent ovarian carcinoma.

PMID- 23162644
TI  - Primary giant lymphoma of the right thigh: A case report and brief review of the
      literature.
AB  - Primary soft tissue non-Hodgkin lymphoma (NHL) of the extremities is very rare.
      The clinical features of NHL mimic those of other soft tissue tumors,
      particularly sarcoma; however, they should be differentiated, as the treatment
      and prognosis are completely different. In this study, the case of a 68-year-old
      female with a giant mass, movement disorder, numbness and painful sensations in
      the right thigh is presented. Magnetic resonance (MR) imaging revealed a huge
      circle-shaped mass. Fine needle aspiration cytology (FNAC) of the tumor
      demonstrated neoplastic small, round cells. The tentative diagnosis was of a
      mesenchymal sarcoma. The right thigh was amputated. On histological examination
      of the amputated extremity, the diagnosis was found to be large B cell lymphoma.
      Primary soft tissue NHL of the extremities is a systemic malignant disease and is
      sensitive to chemo-therapy and radiotherapy. The histological diagnosis should be
      identified as far as possible before the tumor is widely excised.

PMID- 23162645
TI  - miR-155 and miR-31 are differentially expressed in breast cancer patients and are
      correlated with the estrogen receptor and progesterone receptor status.
AB  - The purpose of the present study was to determine the tissue and plasma levels of
      microRNA (miR)-155 and miR-31 in 67 patients with invasive intraductal breast
      cancer and their correlation with the clinicopathological characteristics. Using
      a quantitative real-time-PCR (qRT-PCR) assay, it was demonstrated that the plasma
      levels of miR-155 and miR-31 in patients were 6- and 5-fold higher than those in
      healthy individuals, respectively (P<0.05). In cancerous tissues, miR-155
      expression levels were 5-fold higher compared with those in non-cancerous tissues
      (P<0.05), whereas no difference was observed with miR-31 expression (P>0.05). The
      expression levels of miR-155, but not miR-31, were inversely correlated with
      estrogen receptor (ER) and progesterone receptor (PR) expression (ER, r=-0.353,
      P=0.003; PR, r=-0.357, P=0.003). The tissue and plasma levels of miR-155 and miR
      31 were not correlated with epidermal growth factor receptor-2 (HER-2) expression
      levels. Furthermore, high levels of plasma miR-155 and miR-31 were identified in
      the tumors of TNM stage II, lymph node metastasis 0-3 and tumor sizes of 2-5 cm
      in patients who were aged over 52 years. miR-155 was mainly expressed in patients
      with a pathology score of 3 for ER or PR expression; miR-31 expression was higher
      in patients with a pathology score of 2. These results suggest that miR-155 and
      miR-31 are differentially expressed in breast cancer patients. Their correlation
      with the clinicopathological characteristics may aid the diagnosis and treatment
      of invasive intraductal breast cancer.

PMID- 23162646
TI  - Downregulation of KLF4 and the Bcl-2/Bax ratio in advanced epithelial ovarian
      cancer.
AB  - Kruppel-like factor 4 (KLF4) is a key transcriptional regulator of cell
      differentiation and proliferation and an altered expression of KLF4 has been
      reported in a number of human malignancies. In the present study, we investigated
      KLF4 expression and its role in cell proliferation in advanced epithelial ovarian
      cancer (EOC). We compared KLF4, Bcl-2 and Bax transcript levels in ovaries
      isolated from advanced EOC and normal control ovaries. In addition, the KLF4 gene
      was transduced into ovarian cancer cells and transcript levels of Bcl-2 and Bax
      and cell proliferation were analyzed by real-time RT-PCR and MTT assays,
      respectively. Ovarian KLF4 expression and Bcl-2/Bax ratios were downregulated in
      most cases of advanced EOC. In addition, KLF4 overexpression in ovarian cancer
      cells increased the Bcl-2/Bax ratio. However, MTT analysis indicated that the
      overexpression of KLF4 had no effect on the proliferation of ovarian cancer
      cells. The inactivation of KLF4 is frequently observed in ovarian cancers and a
      reduced expression of KLF4 in the ovarian cancers may lead to a reduction in the
      Bcl-2/Bax ratio. The latter has a role in predicting cancer grade, although its
      exact role in ovarian carcinogenesis requires clarification.

PMID- 23162647
TI  - Changes in microRNA expression in the MG-63 osteosarcoma cell line compared with
      osteoblasts.
AB  - Osteosarcoma (OS) is the most common primary malignant bone tumor, particularly
      in adolescents and young adults. Early diagnosis remains a significant problem in
      the clinical treatment of OS as we remain far from a comprehensive understanding
      of the molecular genetic mechanisms and the biology involved. In addition,
      microRNAs (miRNAs or miRs), a large family of small non-coding RNAs, may provide
      a greater understanding of OS as they play a complex role in gene expression
      regulation in vitro and in vivo. In the current study, the differential
      expression profiles of miRNAs between OS and osteoblast cell lines were
      investigated by miRNA microarrays and real-time quantitative PCR (RT-qPCR). A
      total of 268 miRNAs were identified that were significantly dysregulated in OS
      compared with the osteoblast cell line, including miR-9, miR-99, miR-195, miR
      148a and miR-181a, which had been validated as overexpressed, and miR-143, miR
      145, miR-335 and miR-539, which were confirmed to be downregulated. This
      differential expression may aid future OS diagnosis and prognosis prediction and
      illustration of the potential mechanisms in the oncogenesis, development and
      metastasis of OS. Bioinformatic research on these differentially expressed miRNAs
      suggests that they are able to regulate the biological behaviors of OS in a
      complex and effective manner. Further study on the function of these miRNAs is
      likely to provide new insights into OS biology and treatment.

PMID- 23162648
TI  - Small molecules in combination with conventional chemotherapeutic drugs: Light at
      the end of the tunnel?
AB  - Recent studies have shown BI2536 and bortezomib to be effective in squamous cell
      carcinoma of the head and neck (SCCHN) cell lines. In this systemic in vitro
      study, we examined the antitumor effect of the small molecules BI2536 and
      bortezomib in combination with cisplatin or docetaxel in nine squamous cell
      carcinoma cell lines, most of head and neck origin. Dose escalation studies were
      performed with these cell lines using bortezomib, BI2536, cisplatin and docetaxel
      in cell line-specific concentrations. Growth inhibitory and proapoptotic effects
      were measured quantitatively using cytohistology and the Human Apoptosis Array
      kit. The combination of bortezomib and BI2536 with cisplatin or docetaxel showed
      a significantly higher antiproliferative and apoptotic activity in all SCCHN cell
      lines investigated compared with single agent cisplatin or docetaxel alone
      (P<=0.021). Combination of conventional chemotherapeutic drugs, such as cisplatin
      and docetaxel, with small molecules in the clinical setting may enhance the
      antitumor activity of these agents and may lead to less toxic side-effects and a
      more effective cancer therapy.

PMID- 23162649
TI  - Dermatofibrosarcoma protuberans: Our experience of 59 cases.
AB  - Dermatofibrosarcoma protuberans (DFSP) is a rare soft tissue tumor with
      intermediate malignancy. It is initially located on the skin from where it is
      able to infiltrate the deep structures and has a tendency to recur locally
      following inadequate excision. A t(17;22)(q22;q13) chromosome trans-location is
      the main cytogenetic alteration responsible for the onset of DFSP. Treatment
      options include complete surgical excision by performing conventional surgery
      with wide margins (>3 cm) or Mohs micrographic surgery. A retrospective study was
      conducted in our Department of Plastic and Reconstructive Surgery and all data
      were collected from medical records of 59 DFSP patients within this department
      from 1999 to 2011. A total of 13 of 59 (22%) cases were treated with conventional
      excision; 3 (5%) cases resulted in tumor-free margins, 8 (14%) cases required
      surgical revision and 2 (3%) cases lead to recurrence. A total of 46 of 59 (78%)
      cases were treated with wide excision; 43 (73%) cases resulted in tumor-free
      margins, 3 (5%) cases required surgical revision and 0 (0%) cases lead to
      recurrence. In conclusion, the data collected reveal the controversy surrounding
      the adoption of general guidelines regarding safe margins. Further studies are
      required to investigate the possibility of obtaining genotypically altered
      margins from margins that may appear phenotypically healthy.

PMID- 23162650
TI  - Single nucleotide polymorphisms in the HIF-1alpha gene and chemoradiotherapy of
      locally advanced rectal cancer.
AB  - The aim of this study was to investigate the predictive impact of polymorphisms
      in the HIF-1alpha gene on the response to chemoradiotherapy (CRT) in rectal
      cancer. This study included two cohorts of patients with locally advanced rectal
      cancer receiving long-course CRT. The HIF-1alpha C1772T (rs11549465), G1790A
      (rs11549467) and c(*)191T>C (rs2057482) polymorphisms were investigated in the
      test cohort (n=65), and HIF-1alpha c(*)191T>C was analysed in the validation
      cohort (n=198). No correlations were identified between the polymorphisms and
      clinicopathological factors. The HIF-1alpha C1772T and HIF-1alpha G1790A
      polymorphisms demonstrated no correlation with tumour response to CRT in the test
      cohort. The HIF-1alpha c(*)191T>C CC genotype was marginally associated with a
      higher rate of complete tumour response (P=0.05) in the test cohort, while the
      HIF-1alpha c(*)191T>C CC genotype was associated with a poor tumour response
      (P=0.03) in the validation cohort. In conclusion, these results suggest that HIF
      1alpha polymorphisms have no value as predictors of response to neoadjuvant CRT
      in rectal cancer. The results of the HIF-1alpha c(*)191T>C in two cohorts differ
      and emphasise the importance of biomarker validation.

PMID- 23162651
TI  - Prevention of human adenocarcinoma with CpG-ODN in a mouse model.
AB  - CpG-ODNs activate various immune cell subsets and induce the production of
      numerous cytokines. To determine whether a CpG-ODN-activated innate immune
      system, without the adaptive immune system, was capable of protecting against
      cancer cell growth, NOD/SCID mice, which do not have T or B cell function but
      have a functional innate immune system, were used as a model system. NOD/SCID
      mice were injected subcutaneously with human prostate cancer cells followed by
      subcutaneous injection of incremental doses of CpG-ODNs. CpG-ODNs displayed a
      dose-related antitumoral effect leading to the prevention of tumor growth. These
      results indicate that ODNs are capable of activating the innate immune system and
      destroying human cancer cells in the absence of the adaptive immune system.

PMID- 23162652
TI  - A mimic of phosphorylated prolactin induces apoptosis by activating AP-1 and
      upregulating p21/waf1 in human prostate cancer PC3 cells.
AB  - A mimic of phosphorylated prolactin (S179D PRL) has been demonstrated to inhibit
      prostate cancer cell growth in vitro and in vivo; however, the mechanisms
      involved in this process remain unknown. In this study, we identified that a four
      day treatment of S179D PRL (1 MUg/ml) in human prostate PC3 cancer cells
      activated JNK, c-fos and c-jun, and led to apoptosis. We also demonstrated that
      p21/waf1 was upregulated in cells transfected with the human PRL receptor (S1b)
      following a four-day incubation with S179D PRL (1 MUg/ml). Once the cells were
      cotransfected with S1b and either c-fos, c-jun or the c-fos/c-jun constructs for
      24 h, S17D PRL activated JNK, c-fos and c-jun, and induced apoptosis in the c
      fos/c-jun transfected cells. Additionally, S179D PRL upregulated p21 luciferase
      activity in the cells transfected with the S1b, activating protein-1 (AP-1) (7x)
      Luc or p21 Luc constructs. SP600125 (25 MUM), a JNK blocker, inhibited the
      upregulation of AP-1 Luc and p21 Luc in the c-fos/c-jun transfected cells. These
      results demonstrate that S179D PRL activates JNK and AP-1, which leads to p21
      upregulation and apoptosis in human prostate PC3 cancer cells.

PMID- 23162653
TI  - Small duodenal gastrointestinal stromal tumor presenting with acute bleeding
      misdiagnosed as hemobilia: Two case reports.
AB  - Only 3-5% of gastrointestinal stromal tumors (GISTs) are located in the duodenum.
      They are associated with an increased risk of fatal gastrointestinal bleeding,
      which is a primary manifestation. A small GIST (less than 2 cm in size) is easily
      confused with a duodenal papilla. In the 2 cases presented in this study,
      endoscopic examination alone resulted in a misdiagnoses of hemobilia. To the best
      of our knowledge, this is the first case report of this type in the literature.
      Patient 1 is a 66-year-old male who was admitted to The Second Affiliated
      Hospital of Dalian Medical University with syncope. Emergent upper
      gastrointestinal endoscopy identified bleeding from what appeared to be a
      duodenal papilla, and the patient was diagnosed with hemobilia. However, the
      angiography did not support this result. To save the patient's life, an
      exploratory laparotomy was conducted. We identified a small tumor in the
      descending part of the duodenum and a wedge resection was successfully conducted.
      The final diagnosis was duodenal GIST with no further risk to the patient.
      Patient 2 is a 71-year-old female who was admitted to the hospital diagnosed with
      hemobilia. The patient underwent a barium swallow examination and a contrast
      enhanced computed tomography (CT) scan, in which a tumor on the descending part
      of the duodenum was identified. Patient 2 also underwent a wedge resection. The
      final diagnosis was duodenal GIST with no further risk to the patient.
      Gastroscopy may be a useful procedure for duodenal GIST diagnosis; however, the
      endoscopic findings may be confused with hemobilia when the tumor diameter is
      less than 2 cm in size and heavily accompanied with blood clots. A barium swallow
      examination and contrast-enhanced CT may prevent a misdiagnosis of hemobilia.

PMID- 23162654
TI  - Evaluation of carboplatin dosing in non-small cell lung carcinoma patients using
      Calvert formula and Cockroft and Gault equation for glomerular filtration rate
      estimation.
AB  - The aim of this study was to evaluate the reliability of the Cockroft and Gault
      (CG) equation for glomerular filtration rate (GFR) estimation in carboplatin
      dosing based on the Calvert formula. The records of 117 patients with advanced
      non-small cell lung carcinoma treated with carboplatin were retrospectively
      analyzed. Theoretical carboplatin doses derived from the Calvert formula using
      the CG equation were calculated for each chemotherapy cycle. Fluctuations in the
      theoretical carboplatin doses were analyzed, and discrepancies between actual
      carboplatin doses prescribed by the physician and theoretical doses were
      assessed. It was found that, compared with the first-cycle dose, subsequent
      theoretical doses were more than 10% higher in 79/320 cycles (24.7%) and more
      than 10% lower in 53/320 cycles (16.6%; P=0.015). A body mass index greater than
      or equal to 30 was associated with a tendency for increased CG-estimated GFR
      during subsequent chemotherapy cycles (P=0.009). Physicians tended to lower the
      prescribed dose (32.2% of the cycles) by using a higher serum creatinine (Scr)
      level for dose calculation than was actually measured. We concluded that Calvert
      formula-derived carboplatin doses fluctuate widely during repeated cycles when
      actual Scr is used for CG-estimated GFR. The measurement of 24-h creatinine
      clearance is advised as an alternative in selected patients with reduction in
      serum creatinine observed during treatments.

PMID- 23162655
TI  - Metformin inhibits leptin-induced growth and migration of glioblastoma cells.
AB  - Metformin, a derivative of biguanide, is a first-line therapy for type 2 diabetes
      mellitus. Since the drug has been shown to significantly reduce the risk of
      various cancers and cancer mortality in diabetic patients, it is being considered
      as a potential anticancer therapeutic or preventive agent. In cellular models,
      metformin inhibits the growth of many types of cancer cells; however, its effects
      on glioblastoma multi-forme (GBM) are not well characterized. Here, we analyzed
      the effects of metformin on the growth and migration of LN18 and LN229 GBM cells
      cultured under basal conditions or exposed to leptin, a cytokine that has
      recently been implicated in GBM development. We found that 2-16 mM metformin
      reduced basal and leptin-stimulated growth of GBM cells in a dose-dependent
      manner. Furthermore, the drug significantly inhibited the migration of GBM cells.
      The action of metformin was mediated through the upregulation of its main
      signaling molecule, the adenosine monophosphate-activated protein kinase (AMPK),
      as well as through the downregulation of the signal transducer and activator of
      transcription 3 (STAT3) and the Akt/PKB serine/threonine protein kinase. In
      leptin-treated cells, the drug reversed the effects of the cytokine on the AMPK
      and STAT3 pathways, but modulated Akt activity in a cell-dependent manner. Our
      results suggest that metformin or similar AMPK-targeting agents with optimized
      blood-brain-barrier penetrability could be developed as potential treatments of
      GBM and could be used in conjunction with other target drugs such as leptin
      receptor antagonists.

PMID- 23162656
TI  - Carboplatin and bevacizumab for recurrent malignant glioma.
AB  - Over 65,000 primary brain tumors are diagnosed annually in the US alone.
      Malignant gliomas represent more than one-third of such cases. Despite advances
      in neuroimaging, surgical techniques, radiotherapy and chemotherapy, the survival
      rate of this disease remains poor. The introduction of agents which disrupt the
      function of vascular endothelial growth factor (VEGF) and its receptors to glioma
      therapy has resulted in an unusually high percentage of patients experiencing
      radiographic responses. Bevacizumab, approved by the Food and Drug Administration
      for the treatment of recurrent glioblastoma in 2009, has changed the field of
      neuro-oncology. The drug has been utilized as a single agent and in combination
      with the classic cytotoxic agents typically applied in this setting. Numerous
      studies have reported high response rates and encouraging extensions of time-to
      progression. The optimal schedule and combination of bevacizumab with alternative
      drugs has not been identified. The current study presents the results of a
      retrospective analysis of the combination therapy utilizing bevacizumab with the
      alkylating agent carboplatin in patients with recurrent malignant glioma.

PMID- 23162657
TI  - High-intensity focused ultrasound compared with irradiation for ovarian
      castration in premenopausal females with hormone receptor-positive breast cancer
      after radical mastectomy.
AB  - The aim of the current study was to determine the feasibility, efficacy and
      safety of ovarian castration by high-intensity focused ultrasound (HIFU) in
      premenopausal patients with estrogen receptor (ER)(+)/progesterone receptor
      (PR)(+) breast cancer subsequent to radical mastectomy. A total of 88
      premenopausal females with pathologically confirmed ER(+)/PR(+) breast cancer
      following radical mastectomy were randomly and equally divided into two groups
      that received HIFU therapy or radiation treatment. HIFU therapy was applied twice
      at an interval of three days and radiotherapy was administered to a total
      prescribed dose of D(T) 18 Gy in nine fractions over 11 days. Outcome measures
      included serum levels of estradiol and estrone, the Kupperman index and the
      incidence of secondary amenorrhea. Adverse events were monitored and recorded.
      All patients were followed up for 12 months. Serum levels of estradiol and
      estrone were comparable prior to treatment between the HIFU and radiation
      treatment groups. One month following treatment, serum levels of estradiol and
      estrone were significantly decreased in the two groups, but a greater decline was
      observed in the HIFU treatment group (P<0.01 and 0.05, respectively). In
      addition, more patients developed severe menopausal symptoms and amenorrhea in
      the HIFU therapy group compared with the radiotherapy group (P<0.01 for the two
      groups). A total of 3 months following treatment, serum levels of estradiol and
      estrone and the distribution of patients with severe, moderate and mild
      menopausal symptoms were comparable between the two groups. Following nine
      menstrual cycles, the incidence of amenorrhea reached 100% in the two groups.
      HIFU therapy is superior to radiotherapy for ovarian castration in premenopausal
      females with ER(+)/PR(+) breast cancer subsequent to radical mastectomy in terms
      of its minimal invasiveness and faster efficacy. HIFU represents a feasible non
      surgical approach for ovarian castration.

PMID- 23162658
TI  - High levels of beta-catenin promote IFNgamma-induced apoptosis in hepatocellular
      carcinoma cells.
AB  - beta-catenin is a multifunctional protein that is involved in cellular structure
      and the Wnt/beta-catenin signaling pathway. Wnt/beta-catenin signaling is
      believed to be an inducer of cell proliferation in different tumors. However, in
      certain physiological contexts beta-catenin also promotes apoptosis. High levels
      of beta-catenin are found in a number of cancer cell types. Recent studies have
      shown that beta-catenin may be correlated with carcinogenesis. Its effects and
      interaction with interferon (IFN)gamma signaling in hepatocellular carcinoma
      (HCC) cells remains unknown. In the present study, high levels of beta-catenin
      did not induce antiproliferative effects or apoptosis and did not lead to changes
      in the levels of caspases or activated STATs. However, high levels of beta
      catenin did cause positive p53 accumulation and Bcl-XL downregulation in HepG2
      cells, a HCC cell line. When treated with IFNgamma, apoptosis was induced more
      rapidly compared with cells with low beta-catenin levels (P<0.05), whereas
      caspases 3, 8 and 9 were markedly activated. The caspase inhibitor Z-VAD-FMK and
      the STAT3 inhibitor blocked this IFNgamma-induced apoptosis. Therefore, we report
      that high levels of beta-catenin promote IFNgamma-induced apoptosis in HCC in a
      caspase- and STAT3-dependent manner, and facilitate the activation of executor
      caspases, possibly via regulation of p53 and Bcl-XL levels. These findings may
      provide foundations for the development of new IFN-based therapies against liver
      cancer.

PMID- 23162659
TI  - Differential proteomic analysis of pathway biomarkers in human breast cancer by
      integrated bioinformatics.
AB  - The aim of this study was to better understand the altered functional modules in
      breast cancer at pathway and network levels. An integrated bioinformatics
      analysis of differentially expressed proteins in human breast cancer was
      performed. Breast cancer protein profiles were constructed by data mining
      proteins in literature and public databases, including 1031 proteins with 153
      secretory and 69 cell surface proteins. An experimental investigation was
      performed by two-dimensional electrophoresis, and 4 proteins were further
      validated by western blotting. Enriched bioinformatics functions were clustered.
      This study may be used as a reference in further studies to help identify the
      underlying biological interactions associated with breast cancer and discover
      potential cancer targets.

PMID- 23162660
TI  - Endogenous cGMP-dependent protein kinase reverses EGF-induced MAPK/ERK signal
      transduction through phosphorylation of VASP at Ser239.
AB  - In our previous study, we demonstrated that type II cGMP-dependent protein kinase
      (PKG II) was expressed at lower levels in different human cancer cell lines and
      that exogenous PKG II inhibited epidermal growth factor (EGF)-induced MAPK/ERK
      signaling. In order to investigate its functions further in this signaling
      pathway, it is necessary to elucidate whether endogenous PKG has the same effect
      or not. This study aimed to investigate the possible inhibitory effect of
      endogenous PKG activity on EGF-induced MAPK/ERK signal transduction in human lung
      cancer cells and its mechanism. Human small cell lung carcinoma cells (SCLCs)
      were treated with the PKG-selective cGMP analog 8-pCPT-cGMP to activate
      endogenous PKG, EGF and cGMP followed by EGF, respectively. The results showed
      that increased endogenous PKG activity inhibited the EGF-induced phosphorylation
      of the epidermal growth factor receptor (EGFR) and the binding between Sos1 and
      Grb2. In addition, EGF-triggered Ras activation was reversed by increased
      endogenous PKG activity. While the EGF-induced phosphorylation of MEK and ERK
      were inhibited by increased endogenous PKG activity, there was a significant
      increase of phosphorylated vasodilator-stimulated phosphoprotein (p-VASP) at
      Ser239. Furthermore, we investigated whether endogenous PKG exerted its effects
      on EGF-induced MAPK/ERK signaling through phosphorylation of VASP at Ser239.
      Downregulation of the levels of p-VASP Ser239 by point mutation blocked the
      effects of endogenous PKG on EGF-induced MAPK/ERK signal transduction. The data
      shown here suggest that endogenous PKG reverses the EGF-induced MAPK/ERK
      signaling pathway by phosphorylating VASP at Ser239.

PMID- 23162661
TI  - A novel taspine analog, HMQ1611, inhibits growth of non-small cell lung cancer by
      inhibiting angiogenesis.
AB  - In the present study, we investigated the antitumor activity of HMQ1611, a novel
      synthetic taspine derivative, in vivo and evaluated associated potential
      antiangiogenesis mechanisms. The proliferation of A549 cells was examined by WST
      1 assay in vitro. Tube formation and lung tissue vessel models were used to
      observe the antiangiogenic activity of HMQ1611. In addition, vascular enodthelial
      growth factor (VEGF) secretion and KDR kinase activities were measured by ELISA
      and the HTRF((r))KinEASE(TM)-TK assay. In vivo, the antitumor activity was
      assessed by implantation of A549 cells in athymic mice. The results showed that
      HMQ1611 inhibited A549 cell proliferation and VEGF secretion, while it
      significantly inhibited tube formation and tissue vascularization. Furthermore,
      HMQ1611 inhibited A549 xenograft tumor growth. In conclusion, the results of our
      study suggest that HMQ1611 has latent properties for the inhibition of
      angiogenesis which are involved in its antitumor activity.

PMID- 23162662
TI  - Effectiveness of the bevacizumab-irinotecan regimen in the treatment of recurrent
      glioblastoma multiforme: Comparison with other second-line treatments without
      this regimen.
AB  - A retrospective cohort study was conducted to analyse the effectiveness of
      bevacizumab and irinotecan (BVZ/CPT-11) as a second-line treatment in patients
      with primary glioblastoma multiforme (GBM) in comparison with a control group
      that were not administered BVZ/CPT-11 at the first recurrence. The difference in
      overall survival (OS) between the two groups was used as a predictor of
      effectiveness. OS was calculated according to prognostic factors and gender. A
      total of 28 and 32 patients were enrolled in the BVZ/CPT-11 cohort and control
      group, respectively. The median OS was 17.94 months (95% CI, 14.91-20.96) in the
      BVZ/CPT-11 treatment cohort and 10.97 months (95% CI, 7.65-14.30) in the control
      cohort. The results obtained on the effectiveness of BVZ/CPT-11 treatment in
      patients with primary GBM are consistent with data from previous studies. No
      significant differences were identified in OS based on prognostic factors;
      therefore, the latter cannot be used to select patients who would incur the
      greatest benefits from BVZ/CPT-11 treatment.

PMID- 23162663
TI  - Efficacy assessment of pemetrexed treatment of an NSCLC case with brain
      metastasis.
AB  - Non-small cell lung cancers (NSCLCs) are among the most common malignancies.
      Although pemetrexed is often used clinically to cure cancers, its efficacy in
      NSCLC patients with progressive brain metastases remains unclear. Here, we report
      a successful NSCLC (adenocarcinoma) case treated with pemetrexed. The detected
      tumors were treated with 900 mg of pemetrexed disodium (500 mg/m(2)) was
      administered to the patient on day 1, and 40 mg of cisplatin (25mg/m(2)) was
      administered on days 1-3, at the interval of 3 weeks. After two cycles of
      chemotherapy, the brain metastases were reduced. The lesion in the lung was
      reduced as determined by chest CT-scan. Our results suggest that pemetrexed is an
      effective therapy for patients with NSCLC and progressive brain metastases.

PMID- 23162664
TI  - Changes in soluble fibrin levels during the perioperative period of gynecologic
      cancer surgery.
AB  - The purpose of this study was to evaluate the changes in plasma soluble fibrin
      (SF) levels over time in gynecologic cancer patients following surgery.
      Furthermore, we examined the duration of the coagulation stage and determined a
      suitable duration for which thromboprophylaxis with anticoagulant agents should
      be administered. We retrospectively studied 311 patients with invasive
      gynecologic cancer who underwent surgery at Okayama University Hospital, Japan.
      The plasma SF levels were measured serially prior to the operation and on
      postoperative days 0, 1, 3, 5, 7, 10, 14, 21 and 28. The plasma SF levels
      increased rapidly, peaked on postoperative day 1 and then decreased. The SF
      levels of patients with venous thromboembolism (VTE) were significantly different
      from those of VTE-negative patients on postoperative days 0-10. The SF levels on
      each day did not significantly differ between patients treated with chemical
      anticoagulants and those treated mechanically. The plasma SF levels were elevated
      (>=7.0 MUg/ml) in 159 of the 311 patients (51.1%) on one of the days when these
      levels were measured. Among the patients with elevated plasma SF levels, 110
      patients (69.2%) peaked on days 0-3 and only 9 patients (5.7%) peaked on days 21
      28. Although only 1 of the 14 patients (7.1%) who showed peak levels on day 14
      had undergone chemotherapy following surgery, 8 of the 9 patients (88.9%) whose
      levels peaked on days 21-28 had undergone chemotherapy following surgery (P=
      0.0002). In conclusion, the plasma SF levels increased rapidly, peaked on
      postoperative day 1 and then decreased. These levels peaked within 14 days of
      surgery in most cases. Therefore, chemical thromboprophylaxis may be administered
      for at least up to 14 days following surgery.

PMID- 23162665
TI  - microRNA-195 suppresses osteosarcoma cell invasion and migration in vitro by
      targeting FASN.
AB  - microRNAs are involved in different cancer-related processes. miR-195, one of the
      miR-16/15/195/424/497 family members, has been shown to act as a tumor suppressor
      during tumorigenesis. However, the function of miR-195 in osteosarcoma is still
      unclear. In our study, the miR-195 expression level was upregulated in
      osteosarcoma cells, by transfection with miR-195, and the fatty acid synthase
      (FASN) mRNA and protein expression levels were measured by RT-PCR and western
      blotting. Cell migration and invasion was measured using wound healing migration
      and Transwell invasion assays. We found that the upregulation of miR-195 greatly
      decreased cell invasion and the migration of U2OS. We also identified that FASN
      may be a direct target of miR-195 by the luciferase activity assay. These
      findings provide evidence that miR-195 plays a key role in inhibiting
      osteosarcoma cell migration and invasion through targeting FASN, and strongly
      suggest that exogenous miR-195 may have therapeutic value in treating
      osteosarcoma.

PMID- 23162666
TI  - A pilot study of extremely low-frequency magnetic fields in advanced non-small
      cell lung cancer: Effects on survival and palliation of general symptoms.
AB  - The inhibitory effects of magnetic fields (MFs) on tumor cell proliferation in
      vitro and in vivo have been reported in previous studies. However, the effects of
      MFs in the treatment of cancer have not been described in clinical trials. We
      investigated the effects of 420 r/min, 0.4-T extremely low-frequency MFs (ELF
      MFs) on the survival and palliation of general symptoms in 13 advanced non-small
      cell lung cancer (NSCLC) patients. Toxicity and side-effects were assessed
      according to WHO criteria. The treatment area included the primary tumor site,
      metastatic sites and metastatic lymph nodes. Additionally, the patients were
      treated 2 h per day, 5 days per week for 6-10 weeks. The changes in general
      symptoms were analyzed during ELF-MF treatment and 2 weeks after the completion
      of therapy. Results of physical examination, routine analysis of blood, ECG and
      liver function, biochemical and kidney function tests were evaluated before and
      following treatment. All 13 patients were followed up by outpatient service or
      telephone interview. Our results demonstrated that decreased pleural effusion,
      remission of shortness of breath, relief of cancer pain, increased appetite,
      improved physical strength, regular bowel movement and better sleep quality was
      detected in 2 (15.4%), 5 (38.5%), 5 (38.5%), 6 (46.2%), 9 (69.2%), 1 (7.7%) and 2
      (15.4%) patients, respectively. However, the palliation of symptoms in 2 (15.4%)
      patients was observed during therapy and disappeared at treatment termination. No
      severe toxicity or side-effects were detected in our trial. The median survival
      was 6.0 months (95% CI, 1.0-11.0). The 1- and 2-year survival rates were 31.7 and
      15.9%, respectively. This study is the first to describe survival and palliation
      of general symptoms in advanced NSCLC patients treated with ELF-MFs. As an
      effective, well-tolerated and safe treatment choice, ELF-MFs may prolong survival
      and improve general symptoms of advanced NSCLC patients. However, this treatment
      strategy requires further research.

PMID- 23162667
TI  - Tolerability of adjuvant chemotherapy with S-1 after curative resection in
      patients with stage II/III gastric cancer.
AB  - The results of the Japan Clinical Oncology Group trial demonstrated that adjuvant
      chemotherapy with S-1 for stage II/III gastric cancer is effective and suggested
      that this therapy should be adopted as the standard treatment following curative
      D2 gastric dissection. We reviewed treatment outcomes in 58 consecutive patients
      who received adjuvant therapy with S-1 for stage II/III gastric cancer following
      curative D2 dissection; the standard dosage used was determined on the basis of
      the patient body surface area. Twenty-four patients (41.3%) discontinued
      treatment before 12 months. Patients who completed 12 months of adjuvant therapy
      with S-1 were younger and more frequently treated by senior doctors (>15 years of
      experience) than those who did not. However, no differences existed in
      pathological features and surgical procedures between groups. Overall survival
      and relapse-free survival were better in patients who completed 12 months of
      adjuvant therapy with S-1. Fatigue and nausea were associated with
      discontinuation of S-1 treatment. In conclusion, immediately after surgery,
      fatigue and gastrointestinal symptoms of <= grade 2 may have a major impact on
      treatment compliance. Prior to the commencement of S-1 administration, both
      patients and doctors should be made completely aware of the toxicity, compliance
      and efficacy issues associated with this adjuvant therapy.

PMID- 23162668
TI  - Lymph node micrometastases detected by carcinoembryonic antigen mRNA affect long
      term survival and disease-free interval in early-stage lung cancer patients.
AB  - The majority of stage I lung cancer patients undergo a complete resection of
      their tumor; however, they still harbor a considerable risk of mortality due to
      recurrences. A correlation between the presence of lymph node micrometastases and
      poor prognosis has been observed. The aim of this study was to correlate the
      lymph node molecular staging with the 5-year survival and disease-free interval
      following pulmonary lobectomy for non-small cell lung cancer (NSCLC). A
      quantitative real-time reverse transcriptase-polymerase chain reaction (RT-PCR)
      for carcinoembryonic antigen (CEA) mRNA was performed on primary lung tumors and
      regional lymph nodes from 55 surgically resected NSCLC patients classified as
      clinical stage I. CEA mRNA was found to be present in all the primary tumors. RT
      PCR revealed the presence of cancer cells in the lymph nodes of 20 patients
      (36.3%) and routine staining detected lymph node metastases in 11 patients.
      Significant differences in survival and disease-free intervals were observed in
      patients with lymph node micrometastases versus patients with negative lymph
      nodes (P=0.0026 and P=0.0044, respectively). Multivariate analyses confirmed that
      micrometastases were an independent predictor for worse prognosis (P=0.0098) and
      a short disease-free interval (P=0.0137). This study demonstrated strong
      correlations between the molecular detection of lymph node micrometastases and 5
      year survival rates and disease-free interval in patients who underwent pulmonary
      lobectomy for early-stage lung cancer.

PMID- 23162669
TI  - Rationales for the Bernese approaches in acetabular surgery.
AB  - PURPOSE: To present two new approaches to acetabular surgery that were
      established in Berne, and which aim at enhanced visualization and anatomical
      reconstruction of acetabular fractures. METHOD: The trochanteric flip osteotomy
      allows for surgical hip dislocation, and was introduced as a posterior approach
      for acetabular fracture management involving the posterior column and wall. For
      acetabular fractures predominantly involving the anterior column and the
      quadrilateral plate, the Pararectus approach is described. RESULTS: Full exposure
      of the hip joint, as provided by the trochanteric flip osteotomy, facilitates
      anatomical reduction of acetabular or femoral head fractures and safe positioning
      of the anterior column screw in transverse or T-shaped fractures. Additionally,
      the approach enables osteochondral transplantation as a salvage procedure for
      severe chondral femoral head damage and osteoplasty of an associated inadequate
      offset at the femoral head-neck junction. The Pararectus approach allows
      anatomical restoration with minimal access morbidity, and combines advantages of
      the ilioinguinal and modified Stoppa approaches. CONCLUSIONS: Utilization of the
      trochanteric flip osteotomy eases visualization of the superior aspect of the
      acetabulum, and enables the evaluation and treatment of chondral lesions of the
      femoral head or acetabulum and labral tears. Displaced fractures of the anterior
      column with a medialized quadrilateral plate can be addressed successfully
      through the Pararectus approach, in which surgical access is associated with
      minimal morbidity. However, long-term results following the two presented Bernese
      approaches are needed to confirm that in the treatment of complex acetabular
      fractures the rate of poor results in almost one-third of all cases (as currently
      yielded using traditional approaches) might be reduced by the utilization of the
      presented novel approaches.

PMID- 23162670
TI  - Surgical management of osteoporotic pelvic fractures: a new challenge.
AB  - The number and variety of osteoporotic fractures of the pelvis are rapidly
      growing around the world. Such fractures are the result of low-impact trauma. The
      patients have no signs of hemodynamic instability and do not require urgent
      stabilization. The clinical picture is dominated by immobilizing pain in the
      pelvic region. Fractures may be located in both the ventral and the dorsal pelvic
      ring. The current well-established classification of pelvic ring lesions in
      younger adults does not fully reflect the criteria for osteoporotic and
      insufficiency fractures of the pelvic ring. Most osteoporotic fractures are
      minimally displaced and do not require surgical therapy. However, in some
      patients, an insidious progress of bone damage leads to complex displacement and
      instability. Therefore, vertical sacral ala fractures, fracture dislocations of
      the sacroiliac joint, and spinopelvic dissociations are best treated with
      operative stabilization. Angular stable bridge plating, the insertion of a
      transsacral positioning bar, and iliolumbar fixation are operative techniques
      that have been adapted to the low bone mineral density of the pelvic ring and the
      high forces acting on it. 

PMID- 23162671
TI  - Immediate thoracotomy for penetrating injuries: ten years' experience at a Dutch
      level I trauma center.
AB  - BACKGROUND: An emergency department thoracotomy (EDT) or an emergency thoracotomy
      (ET) in the operating theater are both beneficial in selected patients following
      thoracic penetrating injuries. Since outcome-descriptive European studies are
      lacking, the aim of this retrospective study was to evaluate ten years of
      experience at a Dutch level I trauma center. METHOD: Data on patients who
      underwent an immediate thoracotomy after sustaining a penetrating thoracic injury
      between October 2000 and January 2011 were collected from the trauma registry and
      hospital files. Descriptive and univariate analyses were performed. RESULTS:
      Among 56 patients, 12 underwent an EDT and 44 an ET. Forty-six patients sustained
      one or multiple stab wounds, versus ten with one or multiple gunshot wounds.
      Patients who had undergone an EDT had a lower GCS (p < 0.001), lower pre-hospital
      RTS and hospital triage RTS (p < 0.001 and p = 0.009, respectively), and a lower
      SBP (p = 0.038). A witnessed loss of signs of life generally occurred in EDT
      patients and was accompanied by 100 % mortality. Survival following EDT was 25 %,
      which was significantly lower than in the ET group (75 %; p = 0.002). Survivors
      had lower ISS (p = 0.011), lower rates of pre-hospital (p = 0.031) and hospital
      (p = 0.003) hemodynamic instability, and a lower prevalence of concomitant
      abdominal injury (p = 0.002). CONCLUSION: The overall survival rate in our study
      was 64 %. The outcome of immediate thoracotomy performed in this level I trauma
      center was similar to those obtained in high-incidence regions like the US and
      South Africa. This suggests that trauma units where immediate thoracotomies are
      not part of the daily routine can achieve similar results, if properly trained.

PMID- 23162672
TI  - GENE EXPRESSION AND COLLAGEN FIBER MICROMECHANICAL INTERACTIONS OF THE SEMILUNAR
      HEART VALVE INTERSTITIAL CELL.
AB  - The semilunar (aortic and pulmonary) heart valves function under dramatically
      different hemodynamic environments, and have been shown to exhibit differences in
      mechanical properties, extracellular matrix (ECM) structure, and valve
      interstitial cell (VIC) biosynthetic activity. However, the relationship between
      VIC function and the unique micromechanical environment in each semilunar heart
      valve remains unclear. In the present study, we quantitatively compared porcine
      semilunar mRNA expression of primary ECM constituents, and layer- and valve
      specific VIC-collagen mechanical interactions under increasing transvalvular
      pressure (TVP). Results indicated that the aortic valve (AV) had a higher
      fibrillar collagen mRNA expression level compared to the pulmonary valve (PV). We
      further noted that VICs exhibited larger deformations with increasing TVP in the
      collagen rich fibrosa layer, with substantially smaller changes in the spongiosa
      and ventricularis layers. While the VIC-collagen micro-mechanical coupling varied
      considerably between the semilunar valves, we observed that the VIC deformations
      in the fibrosa layer were similar at each valve's respective peak TVP. This
      result suggests that each semilunar heart valve's collagen fiber microstructure
      is organized to induce a consistent VIC deformation under its respective
      diastolic TVP. Collectively, our results are consistent with higher collagen
      biosynthetic demands for the AV compared to the PV, and that the valvular
      collagen microenvironment may play a significant role in regulating VIC function.

PMID- 23162673
TI  - Low-Loss Transmission Lines for High-Power Terahertz Radiation.
AB  - Applications of high-power Terahertz (THz) sources require low-loss transmission
      lines to minimize loss, prevent overheating and preserve the purity of the
      transmission mode. Concepts for THz transmission lines are reviewed with special
      emphasis on overmoded, metallic, corrugated transmission lines. Using the
      fundamental HE(11) mode, these transmission lines have been successfully
      implemented with very low-loss at high average power levels on plasma heating
      experiments and THz dynamic nuclear polarization (DNP) nuclear magnetic resonance
      (NMR) experiments. Loss in these lines occurs directly, due to ohmic loss in the
      fundamental mode, and indirectly, due to mode conversion into high order modes
      whose ohmic loss increases as the square of the mode index. An analytic
      expression is derived for ohmic loss in the modes of a corrugated, metallic
      waveguide, including loss on both the waveguide inner surfaces and grooves.
      Simulations of loss with the numerical code HFSS are in good agreement with the
      analytic expression. Experimental tests were conducted to determine the loss of
      the HE(11) mode in a 19 mm diameter, helically-tapped, three meter long brass
      waveguide with a design frequency of 330 GHz. The measured loss at 250 GHz was
      0.029 +/- 0.009 dB/m using a vector network analyzer approach and 0.047 +/- 0.01
      dB/m using a radiometer. The experimental results are in reasonable agreement
      with theory. These values of loss, amounting to about 1% or less per meter, are
      acceptable for the DNP NMR application. Loss in a practical transmission line may
      be much higher than the loss calculated for the HE(11) mode due to mode
      conversion to higher order modes caused by waveguide imperfections or miter
      bends.

PMID- 23162674
TI  - Ischemic preconditioning attenuates brain edema after experimental intracerebral
      hemorrhage.
AB  - Ischemic preconditioning (IPC) provides protection against subsequent severe
      ischemic injury. A recent study found that cerebral IPC prolongs bleeding time.
      In this study, we examined whether IPC protects against intra-cerebral hemorrhage
      (ICH)-induced brain edema formation and whether IPC affects blood coagulation.
      There were three sets of experiments in this study. In the first set, male
      Sprague-Dawley rats were preconditioned with either 15 min of left middle
      cerebral artery occlusion, an IPC stimulus, or a sham operation. Three days
      later, rats received an infusion of autologous whole blood in the ipsilateral or
      contralateral caudate. Rats were killed 24 h later for brain water content
      measurement. In the second set, rats underwent 15 min of IPC or a sham operation.
      Three days later, rats were used for bleeding and thrombin clotting time tests.
      In the third set, the levels of p44/42 mitogen-activated protein kinases (MAPKs),
      heme oxygenase-1 (HO-1), transferrin (Tf), and transferrin receptor (TfR) in the
      brain 24 or 72 h after IPC were examined. We found that IPC reduced ICH-induced
      brain edema when blood was injected into the ipsilateral caudate but it did not
      when blood was injected into the contralateral caudate. IPC resulted in
      prolongation of bleeding time and thrombin clotting time. IPC also induced the
      activation of p44/42 MAPKs and upregulation of HO-1, Tf, and TfR levels in the
      ipsilateral caudate. These results suggest that IPC protects against ICH-induced
      brain edema formation and decreases blood coagulation. The protection of IPC
      against ICH is mainly due to local factors in the brain and may be related to
      activation of p44/42 MAPKs and upregulation of HO-1, Tf, and TfR. 

PMID- 23162675
TI  - Modeling the combined influence of host dispersal and waterborne fate and
      transport on pathogen spread in complex landscapes.
AB  - Environmental models, often applied to questions on the fate and transport of
      chemical hazards, have recently become important in tracing certain environmental
      pathogens to their upstream sources of contamination. These tools, such as first
      order decay models applied to contaminants in surface waters, offer promise for
      quantifying the fate and transport of pathogens with multiple environmental
      stages and/or multiple hosts, in addition to those pathogens whose environmental
      stages are entirely waterborne. Here we consider the fate and transport
      capabilities of the human schistosome Schistosoma japonicum, which exhibits two
      waterborne stages and is carried by an amphibious intermediate snail host. We
      present experimentally-derived dispersal estimates for the intermediate snail
      host and fate and transport estimates for the passive downstream diffusion of
      cercariae, the waterborne, human-infective parasite stage. Using a one
      dimensional advective transport model exhibiting first-order decay, we simulate
      the added spatial reach and relative increase in cercarial concentrations that
      dispersing snail hosts contribute to downstream sites. Simulation results suggest
      that snail dispersal can substantially increase the concentrations of cercariae
      reaching downstream locations, relative to no snail dispersal, effectively
      putting otherwise isolated downstream sites at increased risk of exposure to
      cercariae from upstream sources. The models developed here can be applied to
      other infectious diseases with multiple life-stages and hosts, and have important
      implications for targeted ecological control of disease spread.

PMID- 23162676
TI  - Voiding Dysfunction Associated with Pudendal Nerve Entrapment.
AB  - Pudendal nerve entrapment (Alcock canal syndrome) is an uncommon source of
      chronic pelvic pain, in which the pudendal nerve is entrapped or compressed. Pain
      is located in the perineal, genital and perianal areas and is worsened by
      sitting. By simple entrapment of the PN without neurogenic damages, pain is
      usually isolated. In neurogenic damages to the PN, genito-anal numbness, fecal
      and/or urinary incontinence can occurred. PNE can be caused by obstetric traumas,
      scarring due to genitoanal surgeries (prolaps procedures!), accidents and
      surgical mishaps. Diagnosis is based on anamnesis, clinical examination including
      vaginal or rectal palpation of the pelvic nerves with selective nerve blockade.
      Pudendal pain non systematic mean PNE since other neuropathies may induce
      pudendal pain. So sacral radiculopathies (sacral nerves roots S#2-4) are
      underestimated etiologies frequently responsible for pudendal pain with
      irradiation in sacral dermatomes, bladder hypersensitivity or in neurogenic
      lesions, bladder retention.

PMID- 23162677
TI  - A DYNAMIC BAYESIAN NONLINEAR MIXED-EFFECTS MODEL OF HIV RESPONSE INCORPORATING
      MEDICATION ADHERENCE, DRUG RESISTANCE AND COVARIATES().
AB  - HIV dynamic studies have contributed significantly to the understanding of HIV
      pathogenesis and antiviral treatment strategies for AIDS patients. Establishing
      the relationship of virologic responses with clinical factors and covariates
      during long-term antiretroviral (ARV) therapy is important to the development of
      effective treatments. Medication adherence is an important predictor of the
      effectiveness of ARV treatment, but an appropriate determinant of adherence rate
      based on medication event monitoring system (MEMS) data is critical to predict
      virologic outcomes. The primary objective of this paper is to investigate the
      effects of a number of summary determinants of MEMS adherence rates on virologic
      response measured repeatedly over time in HIV-infected patients. We developed a
      mechanism-based differential equation model with consideration of drug adherence,
      interacted by virus susceptibility to drug and baseline characteristics, to
      characterize the long-term virologic responses after initiation of therapy. This
      model fully integrates viral load, MEMS adherence, drug resistance and baseline
      covariates into the data analysis. In this study we employed the proposed model
      and associated Bayesian nonlinear mixed-effects modeling approach to assess how
      to efficiently use the MEMS adherence data for prediction of virologic response,
      and to evaluate the predicting power of each summary metric of the MEMS adherence
      rates. In particular, we intend to address the questions: (i) how to summarize
      the MEMS adherence data for efficient prediction of virologic response after
      accounting for potential confounding factors such as drug resistance and
      covariates, and (ii) how to evaluate treatment effect of baseline characteristics
      interacted with adherence and other clinical factors. The approach is applied to
      an AIDS clinical trial involving 31 patients who had available data as required
      for the proposed model. Results demonstrate that the appropriate determinants of
      MEMS adherence rates are important in order to more efficiently predict virologic
      response, and investigations of adherence to ARV treatment would benefit from
      measuring not only adherence rate but also its summary metric assessment. Our
      study also shows that the mechanism-based dynamic model is powerful and effective
      to establish a relationship of virologic responses with medication adherence,
      virus resistance to drug and baseline covariates.

PMID- 23162678
TI  - Partitioning of CH(4) and CO(2) production originating from rice straw, soil and
      root organic carbon in rice microcosms.
AB  - Flooded rice fields are an important source of the greenhouse gas CH(4). Possible
      carbon sources for CH(4) and CO(2) production in rice fields are soil organic
      matter (SOM), root organic carbon (ROC) and rice straw (RS), but partitioning of
      the flux between the different carbon sources is difficult. We conducted
      greenhouse experiments using soil microcosms planted with rice. The soil was
      amended with and without (13)C-labeled RS, using two (13)C-labeled RS treatments
      with equal RS (5 g kg(-1) soil) but different delta(13)C of RS. This procedure
      allowed to determine the carbon flux from each of the three sources (SOM, ROC,
      RS) by determining the delta(13)C of CH(4) and CO(2) in the different incubations
      and from the delta(13)C of RS. Partitioning of carbon flux indicated that the
      contribution of ROC to CH(4) production was 41% at tillering stage, increased
      with rice growth and was about 60% from the booting stage onwards. The
      contribution of ROC to CO(2) was 43% at tillering stage, increased to around 70%
      at booting stage and stayed relatively constant afterwards. The contribution of
      RS was determined to be in a range of 12-24% for CH(4) production and 11-31% for
      CO(2) production; while the contribution of SOM was calculated to be 23-35% for
      CH(4) production and 13-26% for CO(2) production. The results indicate that ROC
      was the major source of CH(4) though RS application greatly enhanced production
      and emission of CH(4) in rice field soil. Our results also suggest that data of
      CH(4) dissolved in rice field could be used as a proxy for the produced CH(4)
      after tillering stage.

PMID- 23162679
TI  - The discovery of N-1 substituted 2-aminobenzimidazoles as zinc-dependent S.
      aureus biofilm inhibitors.
AB  - A diverse 23-compound library of N-1 substituted 2-aminobenzimidazoles was
      synthesized via an efficient three-step process. This small library produced
      several non-toxic biofilm modulators of two strains of MRSA. Preliminary
      mechanistic studies reveal a zinc-dependent mode of action for these compounds.

PMID- 23162680
TI  - Type 2 diabetes care for patients in a tertiary care setting in UAE: a
      retrospective cohort study.
AB  - OBJECTIVE: We aimed to examine the quality of type 2 diabetes mellitus (T2DM)
      care in Al-Ain, in the United Arab Emirates (UAE). DESIGN: A retrospective cohort
      study from 2008 to 2010. SETTING: A diabetes centre located in a tertiary care
      hospital in Al-Ain, UAE. PARTICIPANTS: People with T2DM receiving care from the
      diabetes centre. RESULTS: 382 Emirates patients with T2DM were included in the
      analysis. Overall in 2010, proportions of people with T2DM reaching the following
      targets were: glycated haemoglobin (HbA1c) 41%, low-density lipoprotein (LDL)
      72%, systolic and diastolic blood pressure (SBP/DBP) 47% and 73%, respectively.
      There was a significant improvement from 2008 to 2010, respectively, in the mean
      for the following: (1) HbA1c (8.5% [95% confidence interval, CI: 8.33-8.67]
      versus 7.5% [95% CI: 7.36-7.63]); (2) LDL (2.60 mmol/L [95% CI: 2.51-2.70] versus
      2.27 mmol/L [95% CI: 2.21-2.33]); and (3) SBP (133.1 mmHg [95% CI: 131.7-134.4]
      versus 131.0 [95% CI: 130.1-131.9]). Glycaemic and lipid control were similar in
      men and women; however, HbA1c levels in men and women aged 60+ years were
      significantly lower by (0.7% [P = 0.01] versus 0.8% [P < 0.001], respectively)
      than for those aged between 18 and 39 years. CONCLUSION: This study demonstrates
      that there is encouraging progress in diabetes care in Al-Ain, UAE as reflected
      by the overall improvement in the mean of HbA1c, LDL and SBP, and the increase in
      the number of people reaching the target for the same indicators from 2008 to
      2010. The results however show that there is scope for additional enhancement of
      care, especially for better glycaemic control among young patients and better SBP
      control among men.

PMID- 23162681
TI  - Horner's syndrome following an epidural blood patch.

PMID- 23162682
TI  - Managing patient pathways to achieve lung cancer waiting time targets: mixed
      methods study.
AB  - OBJECTIVES: England's National Health Service (NHS) introduced a 62-day target,
      from referral to treatment, to make lung cancer patient pathways more efficient.
      This study aims to understand pathway delays that lead to breaches of the target
      when patients need care in both secondary and tertiary setting, so more than one
      institution is involved. DESIGN: Mixed methods cross case analysis. SETTING: Two
      tertiary referral hospitals in London. PARTICIPANTS: Database records of 53
      patients were analysed. Nineteen sets of patient notes were used for pathway
      mapping. Seventeen doctors, four nurses, eight managers and administrators were
      interviewed. MAIN OUTCOME MEASURES: Qualitative methods include pathway mapping
      and semi-structured interviews. Quantitative analysis of patient pathway times
      from cancer services records. RESULTS: The majority of the patient pathway
      (68.4%) is spent in secondary centres. There is more variability in the processes
      of secondary centres but tertiary centres do not have perfect processes either.
      Three themes emerged from discussions: information flows, pathway performance and
      the role of the multidisciplinary approach. CONCLUSIONS: The actions of secondary
      centres have a greater influence on whether a patient breaches the 62-day target,
      compared with tertiary centres. Nevertheless variability exists in both, with
      potential for improvement.

PMID- 23162683
TI  - Negative health system effects of Global Fund's investments in AIDS, tuberculosis
      and malaria from 2002 to 2009: systematic review.
AB  - OBJECTIVES: By using the Global Fund as a case example, we aim to critically
      evaluate the evidence generated from 2002 to 2009 for potential negative health
      system effects of Global Health Initiatives (GHI). DESIGN: Systematic review of
      research literature. SETTING: Developing Countries. PARTICIPANTS: All
      interventions potentially affecting health systems that were funded by the Global
      Fund. MAIN OUTCOME MEASURES: Negative health system effects of Global Fund
      investments as reported by study authors. RESULTS: We identified 24 studies
      commenting on adverse effects on health systems arising from Global Fund
      investments. Sixteen were quantitative studies, six were qualitative and two used
      both quantitative and qualitative methods, but none explicitly stated that the
      studies were originally designed to capture or to assess health system effects
      (positive or negative). Only seemingly anecdotal evidence or authors'
      perceptions/interpretations of circumstances could be extracted from the included
      studies. CONCLUSIONS: This study shows that much of the currently available
      evidence generated between 2002 and 2009 on GHIs potential negative health system
      effects is not of the quality expected or needed to best serve the academic or
      broader community. The majority of the reviewed research did not fulfil the
      requirements of rigorous scientific evidence.

PMID- 23162684
TI  - Socioeconomic determinants of non-communicable-diseases among the Cypriot
      population: questionnaire study.
AB  - OBJECTIVE: To investigate the extent to which the socioeconomic status of
      Cypriots is associated with the lifetime prevalence of self-reported non
      communicable disease (NCDs), with emphasis on those accounting for most Death and
      Disability-adjusted Life Years (DALYs) among the population, including
      cardiovascular disease (CVD), metabolic risks and neuropsychiatric disorders.
      DESIGN: A nationally based survey conducted through personal interviews, using a
      structured questionnaire design. SETTING: Cyprus rural and urban areas (excluding
      Turkish-occupied areas). PARTICIPANTS: Four hundred and sixty-five Cypriot adults
      of an average age of 53 years. MAIN OUTCOME MEASURES: Lifetime prevalence of self
      reported NCDs. RESULTS: Most self-reported NCDs were shown to have significant
      associations with socioeconomic status, defined for this study by level of
      education and family income. Education was significantly inversely associated
      with CVD (18.1% at elementary education level (EE); 2.7% at high school education
      level (HE); and 1.7% at University/College education level (UE)), hypertension
      (23.4% at EE; 8.6% at HE; and 2.6% at UE), hypercholesterolaemia (12.8% at EE;
      7.1% at HE; and 5.2% at UE), obesity (10.7% at EE; 4.7% at HE; and 3.5% at UE),
      diabetes (13.8% at EE; 2.4% at HE; and 0.9% at UE), and drug addiction (7.6% at
      EE; 1.6% at HE; and 0.0% at UE). Depression was more frequent amongst middle
      level graduates (3.2% at EE; 5.1% at HE; and 2.6% at UE). Income was
      significantly negatively associated with CVD (r = -0.130, p = 0.005), stress (r =
      -0.103, p = 0.028) and drug addiction (r = -0.117, p = 0.012), and significantly
      positively associated with the 'no problems' statement (r = 0.201, p = 0.000)
      which was reported by almost two fifths of the population. Worth noting is stress
      which, demonstrating no socioeconomic discrimination, was reported by high
      percentages of the population (17.2% of the sample). CONCLUSIONS: Although with
      some limitations, this study has provided initial evidence for the existence of
      socioeconomically determined health inequalities, which may have potentially
      important implications for understanding the deeper aetiology of common NCDs and
      for informing public policies. More research in this area is required to reveal
      the magnitude of NCDS-socioeconomic relation.

PMID- 23162685
TI  - Differences in the classification of hypertensive controlled patient in primary
      care: Cross sectional study.
AB  - OBJECTIVES: To examine differences in blood pressure control using the 2006
      National Institute for Health and Clinical Excellence (NICE) guidelines and the
      2007 Quality and Outcome Framework (QOF) standards. DESIGN: Cross-sectional
      study. SETTING: 28 general practices located in Wandsworth, London. PARTICIPANTS:
      Hypertensive patients aged 17 years and over. MAIN OUTCOMES MEASURES: Percentage
      of hypertensive patients classified as a hypertensive controlled patient (HCP) by
      each standard. RESULTS: 79.5% of patients were classified as a HCP by the QOF
      target and 60.7% by the NICE target. 93% and 14% of practices had more than 70%
      of patients classified as a HPC by using the QOF and NICE targets respectively.
      By applying the QOF target, men aged 45-64 years and 65 years and over had
      significantly higher probability of being classified as a HCP compared to those
      aged 17-44 years, OR 1.34 (1.08-.165) and OR 2.15 (1.61-2.87) respectively.
      Regardless of the target, for men the probability of being classified as a HCP
      increased with age. CONCLUSION: Better achievement of blood pressure control
      targets is present when the less stringent QOF target is used. Men aged 65 years
      and over were more likely to be classified as a HCP. Greater consistency is
      needed between the clinical targets in QOF and NICE guidance.

PMID- 23162686
TI  - Temporal artery biopsy for giant cell arteritis: retrospective audit.
AB  - OBJECTIVES: Temporal artery biopsy (TAB) is performed in suspected cases of sight
      threatening giant cell arteritis (GCA). We aimed to determine the feasibility of
      TAB in patients who are suspected of having GCA. DESIGN, SETTING AND
      PARTICIPANTS: A retrospective audit of all patients undergoing TAB at a single
      teaching hospital between 2005 and 2011, identified from the histopathology
      database. MAIN OUTCOME MEASURES: (1) Clinical profile and biochemical criteria
      associated with positive histology. (2) Proportion of negative histology patients
      who were commenced on steroid therapy. RESULTS: One hundred and fifty-three TAB
      were performed (mean age 70.8 years, men:women = 3:2, 110 Caucasian: 43 Asian).
      Thirty-two biopsies were positive for GCA and 121 were negative. In total, 68
      (61%) of 112 negative TAB patients were clinically diagnosed with GCA despite
      histological findings (P < 0.001). Nine out of 153 biopsies were non-arterial.
      Histologically positive TAB patients were of higher mean age (77.1 [95% CI 74.5
      79.7] versus 69.1 [95% CI 66.7-71.6]; P < 0.001) and had a higher erythrocyte
      sedimentation rate (ESR) (60 [95% CI 46.1-73.9] versus 39.8 [95% CI 34.2-45.3]; P
      < 0.01)] than those with negative histology. CONCLUSIONS: Raised ESR and higher
      age may be the most useful indicators of GCA. Many histologically negative
      individuals were nevertheless clinically diagnosed and managed as GCA.

PMID- 23162687
TI  - History and ethics of hand transplants.
AB  - Hand transplantation is a form of composite tissue allotransplantation, whereby
      the hand of a cadaveric donor is transferred to the forearm of an amputee. The
      aim of such a procedure is to achieve better outcomes in terms of functionality
      and appearance when compared with prosthetics. The microsurgical techniques
      required have been well established for many years. In addition, advances in
      immunosuppressive therapy have meant that hand transplantation is a feasible
      therapeutic option. However this is not a life-saving procedure, requiring
      lifelong antirejection treatment with potentially serious side-effects. Hand
      transplantation is therefore a controversial concept with ethical, financial and
      psychological implications that need careful consideration. Before this treatment
      can be fully accepted, further research is still required; this should be
      directed towards achieving immunological tolerance, while minimizing costs and
      potential side-effects of post-transplant therapy.

PMID- 23162688
TI  - Network cosmology.
AB  - Prediction and control of the dynamics of complex networks is a central problem
      in network science. Structural and dynamical similarities of different real
      networks suggest that some universal laws might accurately describe the dynamics
      of these networks, albeit the nature and common origin of such laws remain
      elusive. Here we show that the causal network representing the large-scale
      structure of spacetime in our accelerating universe is a power-law graph with
      strong clustering, similar to many complex networks such as the Internet, social,
      or biological networks. We prove that this structural similarity is a consequence
      of the asymptotic equivalence between the large-scale growth dynamics of complex
      networks and causal networks. This equivalence suggests that unexpectedly similar
      laws govern the dynamics of complex networks and spacetime in the universe, with
      implications to network science and cosmology.

PMID- 23162689
TI  - Simulating spread of Bluetongue Virus by flying vectors between hosts on pasture.
AB  - Bluetongue is a disease of ruminants which reached Denmark in 2007. We present a
      process-based stochastic simulation model of vector-borne diseases, where host
      animals are not confined to a central geographic farm coordinate, but can be
      distributed onto pasture areas. Furthermore vectors fly freely and display search
      behavior to locate areas with hosts. We also include wind spread of vectors, host
      movements, and vector seasonality. Results show that temperature and seasonality
      of vectors determines the period in which an incursion of Bluetongue may lead to
      epidemic spread in Denmark. Within this period of risk the number of infected
      hosts is affected by temperature, vector abundance, vector behavior, vectors'
      ability to locate hosts, and use of pasture. These results indicate that
      restricted grazing during outbreaks can reduce the number of infected hosts and
      the size of the affected area. The model can be implemented on other vector-borne
      diseases of grazing animals.

PMID- 23162690
TI  - A Bayesian explanation of the 'Uncanny Valley' effect and related psychological
      phenomena.
AB  - There are a number of psychological phenomena in which dramatic emotional
      responses are evoked by seemingly innocuous perceptual stimuli. A well known
      example is the 'uncanny valley' effect whereby a near human-looking artifact can
      trigger feelings of eeriness and repulsion. Although such phenomena are
      reasonably well documented, there is no quantitative explanation for the findings
      and no mathematical model that is capable of predicting such behavior. Here I
      show (using a Bayesian model of categorical perception) that differential
      perceptual distortion arising from stimuli containing conflicting cues can give
      rise to a perceptual tension at category boundaries that could account for these
      phenomena. The model is not only the first quantitative explanation of the
      uncanny valley effect, but it may also provide a mathematical explanation for a
      range of social situations in which conflicting cues give rise to negative,
      fearful or even violent reactions.

PMID- 23162691
TI  - DNA Nanostructure-based Interfacial engineering for PCR-free ultrasensitive
      electrochemical analysis of microRNA.
AB  - MicroRNAs (miRNAs) have been identified as promising cancer biomarkers due to
      their stable presence in serum. As an alternative to PCR-based homogenous assays,
      surface-based electrochemical biosensors offer great opportunities for low-cost,
      point-of-care tests (POCTs) of disease-associated miRNAs. Nevertheless, the
      sensitivity of miRNA sensors is often limited by mass transport and crowding
      effects at the water-electrode interface. To address such challenges, we herein
      report a DNA nanostructure-based interfacial engineering approach to enhance
      binding recognition at the gold electrode surface and drastically improve the
      detection sensitivity. By employing this novel strategy, we can directly detect
      as few as attomolar (<1, 000 copies) miRNAs with high single-base discrimination
      ability. Given that this ultrasensitive electrochemical miRNA sensor (EMRS) is
      highly reproducible and essentially free of prior target labeling and PCR
      amplification, we also demonstrate its application by analyzing miRNA expression
      levels in clinical samples from esophageal squamous cell carcinoma (ESCC)
      patients.

PMID- 23162692
TI  - Cell type-specific activation of AKT and ERK signaling pathways by small
      negatively-charged magnetic nanoparticles.
AB  - The interaction of nanoparticles (NPs) with living organisms has become a focus
      of public and scientific debate due to their potential wide applications in
      biomedicine, but also because of unwanted side effects. Here, we show that
      superparamagnetic iron oxide NPs (SPIONs) with different surface coatings can
      differentially affect signal transduction pathways. Using isogenic pairs of
      breast and colon derived cell lines we found that the stimulation of ERK and AKT
      signaling pathways by SPIONs is selectively dependent on the cell type and SPION
      type. In general, cells with Ras mutations respond better than their non-mutant
      counterparts. Small negatively charged SPIONs (snSPIONs) activated ERK to a
      similar extent as epidermal growth factor (EGF), and used the same upstream
      signaling components including activation of the EGF receptor. Importantly,
      snSPIONs stimulated the proliferation of Ras transformed breast epithelial cells
      as efficiently as EGF suggesting that NPs can mimic physiological growth factors.

PMID- 23162693
TI  - Delocalized single-photon Dicke states and the Leggett-Garg inequality in solid
      state systems.
AB  - We show how to realize a single-photon Dicke state in a large one-dimensional
      array of two-level systems, and discuss how to test its quantum properties. The
      realization of single-photon Dicke states relies on the cooperative nature of the
      interaction between a field reservoir and an array of two-level-emitters. The
      resulting dynamics of the delocalized state can display Rabi-like oscillations
      when the number of two-level emitters exceeds several hundred. In this case, the
      large array of emitters is essentially behaving like a "mirror-less cavity". We
      outline how this might be realized using a multiple-quantum-well structure or a
      dc-SQUID array coupled to a transmission line, and discuss how the quantum nature
      of these oscillations could be tested with an extension of the Leggett-Garg
      inequality.

PMID- 23162694
TI  - Stretchable and highly sensitive graphene-on-polymer strain sensors.
AB  - The use of nanomaterials for strain sensors has attracted attention due to their
      unique electromechanical properties. However, nanomaterials have yet to overcome
      many technological obstacles and thus are not yet the preferred material for
      strain sensors. In this work, we investigated graphene woven fabrics (GWFs) for
      strain sensing. Different than graphene films, GWFs undergo significant changes
      in their polycrystalline structures along with high-density crack formation and
      propagation mechanically deformed. The electrical resistance of GWFs increases
      exponentially with tensile strain with gauge factors of ~10(3) under 2~6% strains
      and ~10(6) under higher strains that are the highest thus far reported, due to
      its woven mesh configuration and fracture behavior, making it an ideal structure
      for sensing tensile deformation by changes in strain. The main mechanism is
      investigated, resulting in a theoretical model that predicts very well the
      observed behavior.

PMID- 23162695
TI  - Does size matter? - Thermoregulation of 'heavyweight' and 'lightweight' wasps
      (Vespa crabro and Vespula sp.).
AB  - In insect groups with the ability of endothermy, the thermoregulatory capacity
      has a direct relation to body mass. To verify this relationship in vespine wasps,
      we compared the thermoregulation of hornets (Vespa crabro), the largest species
      of wasps in Central Europe, with two smaller wasps (Vespula vulgaris and Vespula
      germanica) in the entire range of ambient temperature (T(a): ~0-40 degrees C)
      where the insects exhibited foraging flights.Despite the great difference in body
      weight of Vespula (V. vulgaris: 84.1+/-19.0 mg, V. germanica: 74.1+/-9.6 mg) and
      Vespa (477.5+/-59.9 mg), they exhibited similarities in the dependence of thorax
      temperature on T(a) on their arrival (mean T(th) = 30-40 degrees C) and departure
      (mean T(th) = 33-40 degrees C) at the nest entrance. However, the hornets' thorax
      temperature was up to 2.5 degrees C higher upon arrival and up to 3 degrees C
      lower at departure. The thorax temperature excess (T(th)-T(a)) above ambient air
      of about 5-18 degrees C indicates a high endothermic capacity in both hornets and
      wasps. Heat gain from solar radiation elevated the temperature excess by up to 1
      degrees C. Results show that hornets and wasps are able to regulate their body
      temperature quite well, even during flight. A comparison of flight temperature
      with literature reports on other vespine wasps revealed a dependence of the T(th)
      on the body mass in species weighing less than about 200 mg.

PMID- 23162696
TI  - Antibody to heat shock protein 70 (HSP70) inhibits human T-cell lymphoptropic
      virus type I (HTLV-I) production by transformed rabbit T-cell lines.
AB  - Adult T cell leukemia is a fatal malignant transformation caused by the human T
      cell lymphoptropic virus type I (HTLV-I). HTLV-I is only associated with the
      development of this disease in a small percentage of infected individuals. Using
      two rabbit transformed T-cell lines; RH/K30 (asymptomatic) and RH/K34
      (leukemogenic), we have investigated the expression of heat shock proteins (HSP)
      90 and 70 and the role of anti-HSPs antibodies on virus production. HSPs surface
      expression was higher on RH/K34 than RH/K30 cells. Heat treatment of cells
      increased the expression of HSPs proteins and virus production; HSPs augmentation
      was stabilized after 12 h and virus production reached a maximum between 8 h-12 h
      then returned to normal level after 24 h of culture. Incubation of cells only
      with rabbit anti-HSP 70 antibodies prevented virus production specifically in the
      leukemogenic cell line. The results indicate a relationship between HSP 70 and
      virus production.

PMID- 23162697
TI  - Occurrence and distribution of 13 trichothecene toxins in naturally contaminated
      maize plants in Germany.
AB  - The objective of the present study was to monitor the occurrence and distribution
      of a spectrum of trichothecene toxins in different parts of maize plants.
      Therefore maize plants were sampled randomly from 13 fields in southwest Germany
      and the fractions kernels, cobs, husks, stalks, leaves and rudimentary ears were
      analyzed for eight A-type and five B-type trichothecenes. Each of the toxins was
      found in at least three of the total of 78 samples. The study revealed that both
      A-type and B-type trichothecenes may be present in all parts of the maize plant
      but may be unevenly distributed. For the contents of deoxynivalenol, 3- and 15
      acetyldeoxynivalenol, nivalenol, scirpentriol, 15-monoacetoxyscirpenol, HT-2 and
      T-2 toxin significant differences (p < 0.05) were found between different parts
      of the maize plants whereas no significant differences were observed for
      fusarenon-X, 4,15-diacetoxyscirpenol, neosolaniol, T-2 triol and T-2 tetraol. Up
      to twelve toxins co-occurring in one sample were detected. As a group B-type
      trichothecenes dominated over A-type trichothecenes concerning incidences and
      levels. Contamination was strongest with rudimentary ears based on incidence and
      mean and maximum contents; mean contents with few exceptions tended towards a
      higher level than in other fractions with significant (p < 0.05) differences
      compared to leaves for seven toxins.

PMID- 23162698
TI  - Current situation of mycotoxin contamination and co-occurrence in animal feed-
      focus on Europe.
AB  - Mycotoxins are secondary metabolites produced by fungi especially those belonging
      to the genus Aspergillus, Penicillum and Fusarium. Mycotoxin contamination can
      occur in all agricultural commodities in the field and/or during storage, if
      conditions are favourable to fungal growth. Regarding animal feed, five
      mycotoxins (aflatoxins, deoxynivalenol, zearalenone, fumonisins and ochratoxin A)
      are covered by EU legislation (regulation or recommendation). Transgressions of
      these limits are rarely observed in official monitoring programs. However, low
      level contamination by Fusarium toxins is very common (e.g., deoxynivalenol (DON)
      is typically found in more than 50% of the samples) and co-contamination is
      frequently observed. Multi-mycotoxin studies reported 75%-100% of the samples to
      contain more than one mycotoxin which could impact animal health at already low
      doses. Co-occurrence of mycotoxins is likely to arise for at least three
      different reasons (i) most fungi are able to simultaneously produce a number of
      mycotoxins, (ii) commodities can be contaminated by several fungi, and (iii)
      completed feed is made from various commodities. In the present paper, we
      reviewed the data published since 2004 concerning the contamination of animal
      feed with single or combinations of mycotoxins and highlighted the occurrence of
      these co-contaminations.

PMID- 23162699
TI  - Effectiveness of the high dose/refuge strategy for managing pest resistance to
      Bacillus thuringiensis (Bt) plants expressing one or two toxins.
AB  - To delay resistance development to Bacillus thuringiensis (Bt) plants expressing
      their own insecticide, the application of the Insect Resistance Management
      strategy called "High Dose/Refuge Strategy" (HD/R) is recommended by the US
      Environmental Protection Agency (US EPA). This strategy was developed for Bt
      plants expressing one toxin. Presently, however, new Bt plants that
      simultaneously express two toxins are on the market. We used a mathematical model
      to evaluate the efficiency of the HD/R strategy for both these Bt toxins. As the
      current two-toxin Bt plants do not express two new Cry toxins but reuse one toxin
      already in use with a one-toxin plant, we estimated the spread of resistance when
      the resistance alleles are not rare. This study assesses: (i) whether the two
      toxins have to be present in high concentration, and (ii) the impact of the
      relative size of the refuge zone on the evolution of resistance and population
      density. We concluded that for Bt plants expressing one toxin, a high
      concentration is an essential condition for resistance management. For the
      pyramided Bt plants, one toxin could be expressed at a low titer if the two
      toxins are used for the first time, and a small refuge zone is acceptable.

PMID- 23162700
TI  - Estimation of multi-mycotoxin contamination in South African compound feeds.
AB  - A total of 92 commercial compound feeds from South Africa were investigated for
      various mycotoxins. The data reveal the highest incidence of feed contamination
      for fumonisins (FB) (range: 104-2999 ug/kg) followed by deoxynivalenol (DON)
      (range: 124-2352 ug/kg) and zearalenone (ZEA) (range: 30-610 ug/kg). The
      incidence of ochratoxin A (OTA) and aflatoxins (AF)-contaminated samples were
      generally low, i.e., 4% and 30% of samples with levels ranging between 6.4 and
      17.1 ug/kg (mean: 9.9 ug/kg) for OTA and 0.2 to 71.8 ug/kg (mean: 9.0 ug/kg) for
      AF. No samples contained T-2 toxin or HT-2 toxin. However, all samples analyzed
      were contaminated with at least one mycotoxin with a majority containing several
      mycotoxins. In particular, 3 of 4 positive samples mainly cattle feeds that had
      relatively high contents of OTA (ranging from 7 to 17.1 ug/kg) also contained
      high amounts of AF (>27.5 ug/kg) together with FB, DON and ZEA. Apart from a few
      samples, the levels of mycotoxins may be regarded as safe for livestock
      production in South Africa. However, the persistent co-occurrence of mycotoxins
      in samples, especially those at high concentrations, i.e., AF and OTA, together
      with other mycotoxins studied, may elicit synergistic or additive effects in
      animals. This should raise concern as multiple contaminations may pose a risk to
      livestock production and health.

PMID- 23162701
TI  - Do only small uremic toxins, chromophores, contribute to the online dialysis dose
      monitoring by UV absorbance?
AB  - The aim of this work was to evaluate the contributions of the main chromophores
      to the total UV absorbance of the spent dialysate and to assess removal dynamics
      of these solutes during optical on-line dialysis dose monitoring. High
      performance chromatography was used to separate and quantify UV-absorbing solutes
      in the spent dialysate sampled at the start and at the end of dialysis sessions.
      Chromatograms were monitored at 210, 254 and 280 nm routinely and full absorption
      spectra were registered between 200 and 400 nm. Nearly 95% of UV absorbance
      originates from solutes with high removal ratio, such as uric acid. The
      contributions of different solute groups vary at different wavelengths and there
      are dynamical changes in contributions during the single dialysis session.
      However, large standard deviation of the average contribution values within a
      series of sessions indicates remarkable differences between individual
      treatments. A noteworthy contribution of Paracetamol and its metabolites to the
      total UV absorbance was determined at all three wavelengths. Contribution of
      slowly dialyzed uremic solutes, such as indoxyl sulfate, was negligible.

PMID- 23162702
TI  - Vixapatin (VP12), a c-type lectin-protein from Vipera xantina palestinae venom:
      characterization as a novel anti-angiogenic compound.
AB  - A C-type lectin-like protein (CTL), originally identified as VP12 and lately
      named Vixapatin, was isolated and characterized from Israeli viper Vipera xantina
      palestinae snake venom. This CTL was characterized as a selective alpha2beta1
      integrin inhibitor with anti-melanoma metastatic activity. The major aim of the
      present study was to prove the possibility that this protein is also a potent
      novel anti-angiogenic compound. Using an adhesion assay, we demonstrated that
      Vixapatin selectively and potently inhibited the alpha2 mediated adhesion of K562
      over-expressing cells, with IC(50) of 3 nM. 3 nM Vixapatin blocked proliferation
      of human dermal microvascular endothelial cells (HDMEC); 25 nM inhibited collagen
      I induced migration of human fibrosarcoma HT-1080 cells; and 50 nM rat C6 glioma
      and human breast carcinoma MDA-MB-231 cells. 1 uM Vixapatin reduced HDMEC tube
      formation by 75% in a Matrigel assay. Furthermore, 1 uM Vixapatin decreased by
      70% bFGF-induced physiological angiogenesis, and by 94% C6 glioma-induced
      pathological angiogenesis, in shell-less embryonic quail chorioallantoic membrane
      assay. Vixapatin's ability to inhibit all steps of the angiogenesis process
      suggest that it is a novel pharmacological tool for studying alpha2beta1 integrin
      mediated angiogenesis and a lead compound for the development of a novel anti
      angiogenic/angiostatic/anti-cancer drug.

PMID- 23162703
TI  - Anthrax lethal toxin and the induction of CD4 T cell immunity.
AB  - Bacillus anthracis secretes exotoxins which act through several mechanisms
      including those that can subvert adaptive immunity with respect both to antigen
      presenting cell and T cell function. The combination of Protective Antigen (PA)
      and Lethal Factor (LF) forming Lethal Toxin (LT), acts within host cells to down
      regulate the mitogen activated protein kinase (MAPK) signaling cascade. Until
      recently the MAPK kinases were the only known substrate for LT; over the past few
      years it has become evident that LT also cleaves Nlrp1, leading to inflammasome
      activation and macrophage death. The predicted downstream consequences of
      subverting these important cellular pathways are impaired antigen presentation
      and adaptive immunity. In contrast to this, recent work has indicated that robust
      memory T cell responses to B. anthracis antigens can be identified following
      natural anthrax infection. We discuss how LT affects the adaptive immune response
      and specifically the identification of B. anthracis epitopes that are both
      immunogenic and protective with the potential for inclusion in protein sub-unit
      based vaccines.

PMID- 23162704
TI  - Within-mat variability in anatoxin-a and homoanatoxin-a production among benthic
      Phormidium (cyanobacteria) strains.
AB  - Benthic Phormidium mats can contain high concentrations of the neurotoxins
      anatoxin-a and homoanatoxin-a. However, little is known about the co-occurrence
      of anatoxin-producing and non-anatoxin-producing strains within mats. There is
      also no data on variation in anatoxin content among toxic genotypes isolated from
      the same mat. In this study, 30 Phormidium strains were isolated from 1 cm(2)
      sections of Phormidium-dominated mats collected from three different sites.
      Strains were grown to stationary phase and their anatoxin-a, homoanatoxin-a,
      dihydroanatoxin-a and dihydrohomoanatoxin-a concentrations determined using
      liquid chromatography-mass spectrometry. Each strain was characterized using
      morphological and molecular (16S rRNA gene sequences) techniques. Eighteen
      strains produced anatoxin-a, dihydroanatoxin-a or homoanatoxin-a. Strains
      isolated from each mat either all produced toxins, or were a mixture of anatoxin
      and non-anatoxin-producing genotypes. Based on morphology these genotypes could
      not be separated. The 16S rRNA gene sequence comparisons showed a difference of
      at least 17 nucleotides among anatoxin and non-anatoxin-producing strains and
      these formed two separate sub-clades during phylogenetic analysis. The total
      anatoxin concentration among toxic strains varied from 2.21 to 211.88 mg kg(-1)
      (freeze dried weight), representing a 100 fold variation in toxin content. These
      data indicate that both the relative abundance of anatoxin and non-anatoxin
      producing genotypes, and variations in anatoxin producing capability, can
      influence the overall toxin concentration of benthic Phormidium mat samples.

PMID- 23162706
TI  - Calyculin A from Discodermia calyx is a dual action toxin that blocks calcium
      influx and inhibits protein Ser/Thr phosphatases.
AB  - Calyculin A (Caly A) is cell permeable toxin widely used in cell biology research
      as an inhibitor of type 1 and type 2A protein Ser/Thr phosphatases of the PPP
      family. Here we tested effects of low concentrations of Caly A on proliferation
      of human cancer and non-cancer cell lines. We found that long-term 0.3 nM Caly A
      prevented G1 to S phase cell cycle progression in human Hs-68 fibroblasts and
      ARPE19 epithelial cells, but not human breast cancer MDA-MB-468, MDA-MB-231 and
      MCF7 cells. These conditions produced no change in cyclin D1 levels or in the
      phosphorylation of endogenous proteins. However, acute application of 0.3 nM Caly
      A blocked serum-induced increase in intracellular calcium levels in Hs-68
      fibroblasts, but not in MDA-MB-468 breast cancer cells. We propose that
      subnanomolar Caly A prevents cell cycle progression because it blocks calcium
      uptake by fibroblasts. This probably involves non-selective cation channels and
      cancer cell proliferation was not affected because calcium enters these cells by
      other channels. Our results suggest that calyculin A has dual actions and acts as
      a channel blocker, in addition to its well-established effects as a phosphatase
      inhibitor.

PMID- 23162708
TI  - Laser-scanning photoacoustic microscopy with ultrasonic phased array transducer.
AB  - In this paper, we report our latest progress on proving the concept that
      ultrasonic phased array can improve the detection sensitivity and field of view
      (FOV) in laser-scanning photoacoustic microscopy (LS-PAM). A LS-PAM system with a
      one-dimensional (1D) ultrasonic phased array was built for the experiments. The
      1D phased array transducer consists of 64 active elements with an overall active
      dimension of 3.2 mm * 2 mm. The system was tested on imaging phantom and mouse
      ear in vivo. Experiments showed a 15 dB increase of the signal-to-noise ratio
      (SNR) when beamforming was employed compared to the images acquired with each
      single element. The experimental results demonstrated that ultrasonic phased
      array can be a better candidate for LS-PAM in high sensitivity applications like
      ophthalmic imaging.

PMID- 23162705
TI  - Clinical uses of botulinum neurotoxins: current indications, limitations and
      future developments.
AB  - Botulinum neurotoxins (BoNTs) cause flaccid paralysis by interfering with vesicle
      fusion and neurotransmitter release in the neuronal cells. BoNTs are the most
      widely used therapeutic proteins. BoNT/A was approved by the U.S. FDA to treat
      strabismus, blepharospam, and hemificial spasm as early as 1989 and then for
      treatment of cervical dystonia, glabellar facial lines, axillary hyperhidrosis,
      chronic migraine and for cosmetic use. Due to its high efficacy, longevity of
      action and satisfactory safety profile, it has been used empirically in a variety
      of ophthalmological, gastrointestinal, urological, orthopedic, dermatological,
      secretory, and painful disorders. Currently available BoNT therapies are limited
      to neuronal indications with the requirement of periodic injections resulting in
      immune-resistance for some indications. Recent understanding of the structure
      function relationship of BoNTs prompted the engineering of novel BoNTs to extend
      therapeutic interventions in non-neuronal systems and to overcome the immune
      resistance issue. Much research still needs to be done to improve and extend the
      medical uses of BoNTs.

PMID- 23162709
TI  - In vivo detection of cortical optical changes associated with seizure activity
      with optical coherence tomography.
AB  - The most common technology for seizure detection is with electroencephalography
      (EEG), which has low spatial resolution and minimal depth discrimination. Optical
      techniques using near-infrared (NIR) light have been used to improve upon EEG
      technology and previous research has suggested that optical changes, specifically
      changes in near-infrared optical scattering, may precede EEG seizure onset in in
      vivo models. Optical coherence tomography (OCT) is a high resolution, minimally
      invasive imaging technique, which can produce depth resolved cross-sectional
      images. In this study, OCT was used to detect changes in optical properties of
      cortical tissue in vivo in mice before and during the induction of generalized
      seizure activity. We demonstrated that a significant decrease (P < 0.001) in
      backscattered intensity during seizure progression can be detected before the
      onset of observable manifestations of generalized (stage-5) seizures. These
      results indicate the feasibility of minimally-invasive optical detection of
      seizures with OCT.

PMID- 23162710
TI  - Goniometric measurements of thick tissue using Monte Carlo simulations to obtain
      the single scattering anisotropy coefficient.
AB  - The scattering anisotropy, g, of tissue can be a powerful metric of tissue
      structure, and is most directly measured via goniometry and fitting to the Henyey
      Greenstein phase function. We present a method based on an independent
      attenuation measurement of the scattering coefficient along with Monte Carlo
      simulations to account for multiple scattering, allowing the accurate
      determination of measurement of g for tissues of thickness within the quasi
      ballistic regime. Simulations incorporating the experimental geometry and bulk
      optical properties show that significant errors occur in extraction of g values,
      even for tissues of thickness less than one scattering length without modeling
      corrections. Experimental validation is provided by determination of g in mouse
      muscle tissues and it is shown that the obtained values are independent of
      thickness. In addition we present a simple deconvolution-based method and show
      that it provides excellent estimates for high anisotropy values (above 0.95) when
      coupled with an independent attenuation measurement.

PMID- 23162711
TI  - Large-field high-speed polarization sensitive spectral domain OCT and its
      applications in ophthalmology.
AB  - We present a novel spectral domain polarization sensitive OCT system (PS-OCT)
      that operates at an A-scan rate of 70 kHz and supports scan angles of up to 40
      degrees  * 40 degrees . The high-speed imaging allows the acquisition of up to
      1024 * 250 A-scans per 3D scan, which, together with the large field of view,
      considerably increases the informative value of the images. To demonstrate the
      excellent performance of the new PS-OCT system, we imaged several healthy
      volunteers and patients with various diseases such as glaucoma, AMD, Stargardt's
      disease, and albinism. The results are compared with clinically established
      methods such as scanning laser polarimetry and autofluorescence.

PMID- 23162712
TI  - Retinal, anterior segment and full eye imaging using ultrahigh speed swept source
      OCT with vertical-cavity surface emitting lasers.
AB  - We demonstrate swept source OCT utilizing vertical-cavity surface emitting laser
      (VCSEL) technology for in vivo high speed retinal, anterior segment and full eye
      imaging. The MEMS tunable VCSEL enables long coherence length, adjustable
      spectral sweep range and adjustable high sweeping rate (50-580 kHz axial scan
      rate). These features enable integration of multiple ophthalmic applications into
      one instrument. The operating modes of the device include: ultrahigh speed, high
      resolution retinal imaging (up to 580 kHz); high speed, long depth range anterior
      segment imaging (100 kHz) and ultralong range full eye imaging (50 kHz). High
      speed imaging enables wide-field retinal scanning, while increased light
      penetration at 1060 nm enables visualization of choroidal vasculature.
      Comprehensive volumetric data sets of the anterior segment from the cornea to
      posterior crystalline lens surface are also shown. The adjustable VCSEL sweep
      range and rate make it possible to achieve an extremely long imaging depth range
      of ~50 mm, and to demonstrate the first in vivo 3D OCT imaging spanning the
      entire eye for non-contact measurement of intraocular distances including axial
      eye length. Swept source OCT with VCSEL technology may be attractive for next
      generation integrated ophthalmic OCT instruments.

PMID- 23162713
TI  - Optical clearing of archive-compatible paraffin embedded tissue for multiphoton
      microscopy.
AB  - Standard histopathology techniques (including paraffin embedding) are
      incompatible with thick tissue multiphoton imaging, and standard clearing
      techniques on those specimens destroy some molecular information. We demonstrate
      multiphoton imaging in specimens prepared according to standard histopathology
      techniques. This permits unlabeled 3-dimensional histology on archival tissue
      banks, which is of great value in evaluating prognostic indicators.

PMID- 23162714
TI  - Broadband continuous-wave technique to measure baseline values and changes in the
      tissue chromophore concentrations.
AB  - We present a broad-band, continuous-wave spectral approach to quantify the
      baseline optical properties of tissue and changes in the concentration of a
      chromophore, which can assist to quantify the regional blood flow from dynamic
      contrast-enhanced near-infrared spectroscopy data. Experiments were conducted on
      phantoms and piglets. The baseline optical properties of tissue were determined
      by a multi-parameter wavelength-dependent data fit of a photon diffusion equation
      solution for a homogeneous medium. These baseline optical properties were used to
      find the changes in Indocyanine green concentration time course in the tissue.
      The changes were obtained by fitting the dynamic data at the peak wavelength of
      the chromophore absorption, which were used later to estimate the cerebral blood
      flow using a bolus tracking method.

PMID- 23162715
TI  - Introduction to the BIOMED 2012 Feature Issue.
AB  - The guest editors introduce a feature issue containing papers based on research
      presented at the BIOMED 2012 conference.

PMID- 23162716
TI  - Comment on "Measurement and correction of transverse chromatic offsets for multi
      wavelength retinal microscopy in the living eye".
AB  - An interesting method to measure and correct chromatic magnification offsets in a
      multi-wavelength retinal imaging microscope was recently reported [Harmening et
      al., Biomed. Opt. Express 3, 2066 (2012)]. These values were in part related to
      the ocular transverse chromatic aberration (TCA). This method could be
      potentially used in the future to overcome the fundamental limitation to estimate
      the eye's TCA with ophthalmoscopic (double-pass) configurations.

PMID- 23162717
TI  - Digital focusing of OCT images based on scalar diffraction theory and information
      entropy.
AB  - This paper describes a digital method that is capable of automatically focusing
      optical coherence tomography (OCT) en face images without prior knowledge of the
      point spread function of the imaging system. The method utilizes a scalar
      diffraction model to simulate wave propagation from out-of-focus scatter to the
      focal plane, from which the propagation distance between the out-of-focus plane
      and the focal plane is determined automatically via an image-definition
      evaluation criterion based on information entropy theory. By use of the proposed
      approach, we demonstrate that the lateral resolution close to that at the focal
      plane can be recovered from the imaging planes outside the depth of field region
      with minimal loss of resolution. Fresh onion tissues and mouse fat tissues are
      used in the experiments to show the performance of the proposed method.

PMID- 23162718
TI  - Integration of optical components on-chip for scattering and fluorescence
      detection in an optofluidic device.
AB  - An optofluidic device is demonstrated with photonic components integrated onto
      the chip for use in fluorescence and scatter detection and counting applications.
      The device is fabricated by integrating the optical and fluidic components in a
      single functional layer. Optical excitation on-chip is accomplished via a
      waveguide integrated with a system of lenses that reforms the geometry of the
      beam in the microfluidic channel into a specific shape that is more suitable for
      reliable detection. Separate counting tests by detecting fluorescence and
      scattered signals from 2.5 and 6.0 MUm beads were performed and found to show
      detection reliability comparable to that of conventional means of excitation and
      an improvement over other microchip-based designs.

PMID- 23162719
TI  - Self-calibrated algorithms for diffuse optical tomography and bioluminescence
      tomography using relative transmission images.
AB  - Reconstruction algorithms for diffuse optical tomography (DOT) and
      bioluminescence tomography (BLT) have been developed based on diffusion theory.
      The algorithms numerically solve the diffusion equation using the finite element
      method. The direct measurements of the uncalibrated light fluence rates by a
      camera are used for the reconstructions. The DOT is self-calibrated by using all
      possible pairs of transmission images obtained with external sources along with
      the relative values of the simulated data and the calculated Jacobian. The
      reconstruction is done in the relative domain with the cancelation of any
      geometrical or optical factors. The transmission measurements for the DOT are
      used for calibrating the bioluminescence measurements at each wavelength and then
      a normalized system of equations is built up which is self-calibrated for the
      BLT. The algorithms have been applied to a three dimensional model of the mouse
      (MOBY) segmented into tissue regions which are assumed to have uniform optical
      properties. The DOT uses the direct method for calculating the Jacobian. The BLT
      uses a reduced space of eigenvectors of the Green's function with iterative
      shrinking of the permissible source region. The reconstruction results of the DOT
      and BLT algorithms show good agreement with the actual values when using either
      absolute or relative data. Even a small calibration error causes significant
      degradation of the reconstructions based on absolute data.

PMID- 23162720
TI  - Automatic stent detection in intravascular OCT images using bagged decision
      trees.
AB  - Intravascular optical coherence tomography (iOCT) is being used to assess
      viability of new coronary artery stent designs. We developed a highly automated
      method for detecting stent struts and measuring tissue coverage. We trained a
      bagged decision trees classifier to classify candidate struts using features
      extracted from the images. With 12 best features identified by forward selection,
      recall (precision) were 90%-94% (85%-90%). Including struts deemed insufficiently
      bright for manual analysis, precision improved to 94%. Strut detection statistics
      approached variability of manual analysis. Differences between manual and
      automatic area measurements were 0.12 +/- 0.20 mm(2) and 0.11 +/- 0.20 mm(2) for
      stent and tissue areas, respectively. With proposed algorithms, analyst time per
      stent should significantly reduce from the 6-16 hours now required.

PMID- 23162721
TI  - Tissue dynamics spectroscopy for phenotypic profiling of drug effects in three
      dimensional culture.
AB  - Coherence-gated dynamic light scattering captures cellular dynamics through ultra
      low-frequency (0.005-5 Hz) speckle fluctuations and Doppler shifts that encode a
      broad range of cellular and subcellular motions. The dynamic physiological
      response of tissues to applied drugs is the basis for a new type of phenotypic
      profiling for drug screening on multicellular tumor spheroids. Volumetrically
      resolved tissue-response fluctuation spectrograms act as fingerprints that are
      segmented through feature masks into high-dimensional feature vectors. Drug
      response clustering is achieved through multidimensional scaling with simulated
      annealing to construct phenotypic drug profiles that cluster drugs with similar
      responses. Hypoxic vs. normoxic tissue responses present two distinct phenotypes
      with differentiated responses to environmental perturbations and to
      pharmacological doses.

PMID- 23162722
TI  - Terahertz time-domain spectroscopy for monitoring the curing of dental
      composites.
AB  - We apply terahertz (THz) time-domain spectroscopy for monitoring the curing
      process of three different light-curing dental composites. Exact knowledge of the
      sample thickness is required for a precise determination of the THz dielectric
      parameters, as the materials exhibit shrinkage when they are cured. We find very
      small but significant changes of the THz refractive index and absorption
      coefficient during stepwise light exposure. The changes in the refractive index
      are correlated with changes in the density of the materials. Furthermore, the
      refractive index and the sample thickness are found to give the most reliable
      result for monitoring the curing process of the dental composites.

PMID- 23162723
TI  - An all-fiber-optic endoscopy platform for simultaneous OCT and fluorescence
      imaging.
AB  - We present an all-fiber-optically based endoscope platform for simultaneous
      optical coherence tomography (OCT) and fluorescence imaging. This design entails
      the use of double-clad fiber (DCF) in the endoscope for delivery of OCT source
      and fluorescence excitation light while collecting the backscattered OCT signal
      through the single-mode core and fluorescence emission through the large inner
      cladding of the DCF. Circumferential beam scanning was performed by rotating a 45
      degrees  reflector using a miniature DC motor at the distal end of the endoscope.
      Additionally, a custom DCF coupler and a wavelength division multiplexer (WDM)
      were utilized to seamlessly integrate both imaging modalities to achieve an
      entirely fiber-optically based dual-modality imaging system. We demonstrated
      simultaneous intraluminal 3D OCT and 2D (surface) fluorescence imaging in ex vivo
      rabbit esophagus using the dual-modal endomicroscopy system. Structural
      morphologies (provided by OCT) and fluorophore distribution (provided by the
      fluorescence module) could be clearly visualized, suggesting the potential of the
      dual-modality system for future in vivo and clinical applications.

PMID- 23162724
TI  - Imaging morphodynamics of human blood cells in vivo with video-rate third
      harmonic generation microscopy.
AB  - With a video-rate third harmonic generation (THG) microscopy system, we imaged
      the micro-circulation beneath the human skin without labeling. Not only the speed
      of circulation but also the morpho-hydrodynamics of blood cells can be analyzed.
      Lacking of nuclei, red blood cells (RBCs) shows typical parachute-like and hollow
      core morphology under THG microscopy. Quite different from RBCs, every now and
      then, round and granule rich blood cells with strong THG contrast appear in
      circulation. The corresponding volume densities in blood, evaluated from their
      frequencies of appearance and the velocity of circulation, fall within the
      physiological range of human white blood cell counts.

PMID- 23162725
TI  - Dynamic quantitative phase imaging for biological objects using a pixelated phase
      mask.
AB  - This paper describes research in developing a dynamic quantitative phase imaging
      microscope providing instantaneous measurements of dynamic motions within and
      among live cells without labels or contrast agents. It utilizes a pixelated phase
      mask enabling simultaneous measurement of multiple interference patterns derived
      using the polarization properties of light to track dynamic motions and
      morphological changes. Optical path difference (OPD) and optical thickness (OT)
      data are obtained from phase images. Two different processing routines are
      presented to remove background surface shape to enable quantification of changes
      in cell position and volume over time. Data from a number of different moving
      biological organisms and cell cultures are presented.

PMID- 23162726
TI  - In vivo photothermal optical coherence tomography of gold nanorod contrast
      agents.
AB  - Photothermal optical coherence tomography (PT-OCT) is a potentially powerful tool
      for molecular imaging. Here, we characterize PT-OCT imaging of gold nanorod (GNR)
      contrast agents in phantoms, and we apply these techniques for in vivo GNR
      imaging. The PT-OCT signal was compared to the bio-heat equation in phantoms, and
      in vivo PT-OCT images were acquired from subcutaneous 400 pM GNR Matrigel
      injections into mice. Experiments revealed that PT-OCT signals varied as
      predicted by the bio-heat equation, with significant PT-OCT signal increases at
      7.5 pM GNR compared to a scattering control (p < 0.01) while imaging in common
      path configuration. In vivo PT-OCT images demonstrated an appreciable increase in
      signal in the presence of GNRs compared to controls. Additionally, in vivo PT-OCT
      GNR signals were spatially distinct from blood vessels imaged with Doppler OCT.
      We anticipate that the demonstrated in vivo PT-OCT sensitivity to GNR contrast
      agents is sufficient to image molecular expression in vivo. Therefore, this work
      demonstrates the translation of PT-OCT to in vivo imaging and represents the next
      step towards its use as an in vivo molecular imaging tool.

PMID- 23162727
TI  - Coherent anti-Stokes Raman scattering and spontaneous Raman spectroscopy and
      microscopy of microalgae with nitrogen depletion.
AB  - Microalgae are extensively researched as potential feedstocks for biofuel
      production. Energy-rich compounds in microalgae, such as lipids, require
      efficient characterization techniques to investigate the metabolic pathways and
      the environmental factors influencing their accumulation. The model green alga
      Coccomyxa accumulates significant amounts of triacylglycerols (TAGs) under
      nitrogen depletion (N-depletion). To monitor the growth of TAGs (lipid) in
      microalgal cells, a study of microalgal cells (Coccomyxa sp. C169) using both
      spontaneous Raman and coherent anti-Stokes Raman scattering (CARS) spectroscopy
      and microscopy were carried out. Spontaneous Raman spectroscopy was conducted to
      analyze the components in the algal cells, while CARS was carried out to monitor
      the distribution of lipid droplets in the cells. Raman signals of carotenoid are
      greater in control microalgae compared to N-depleted cells. Raman signals of
      lipid droplets appear after N-depletion and its distribution can be clearly
      observed in the CARS microscopy. Both spontaneous Raman spectroscopy and CARS
      microscopy were found to be suitable analysis tools for microalgae.

PMID- 23162728
TI  - Elliptically polarized light for depth resolved optical imaging.
AB  - It is shown that using elliptically polarized light permits selecting well
      defined subsurface volumes in a turbid medium. This suggests the possibility of
      probing biological tissues at specific depths. First, we present the method and
      preliminary results obtained on an Intralipid phantom. We next report on the
      method's performance on a biological phantom (chicken breast) and, finally, on
      the exposed cortex of an anesthetized rat.

PMID- 23162729
TI  - Comparative studies of l(p)-regularization-based reconstruction algorithms for
      bioluminescence tomography.
AB  - Inverse source reconstruction is the most challenging aspect of bioluminescence
      tomography (BLT) because of its ill-posedness. Although many efforts have been
      devoted to this problem, so far, there is no generally accepted method. Due to
      the ill-posedness property of the BLT inverse problem, the regularization method
      plays an important role in the inverse reconstruction. In this paper, six
      reconstruction algorithms based on l(p) regularization are surveyed. The effects
      of the permissible source region, measurement noise, optical properties, tissue
      specificity and source locations on the performance of the reconstruction
      algorithms are investigated using a series of single source experiments. In order
      to further inspect the performance of the reconstruction algorithms, we present
      the double sources and the in vivo mouse experiments to study their resolution
      ability and potential for a practical heterogeneous mouse experiment. It is hoped
      to provide useful guidance on algorithm development and application in the
      related fields.

PMID- 23162730
TI  - Selective detection of bacterial layers with terahertz plasmonic antennas.
AB  - Current detection and identification of micro-organisms is based on either rather
      unspecific rapid microscopy or on more accurate but complex and time-consuming
      procedures. In a medical context, the determination of the bacteria Gram type is
      of significant interest. The diagnostic of microbial infection often requires the
      identification of the microbiological agent responsible for the infection, or at
      least the identification of its family (Gram type), in a matter of minutes. In
      this work, we propose to use terahertz frequency range antennas for the enhanced
      selective detection of bacteria types. Several microorganisms are investigated by
      terahertz time-domain spectroscopy: a fast, contactless and damage-free
      investigation method to gain information on the presence and the nature of the
      microorganisms. We demonstrate that plasmonic antennas enhance the detection
      sensitivity for bacterial layers and allow the selective recognition of the Gram
      type of the bacteria.

PMID- 23162731
TI  - Real-time eye motion compensation for OCT imaging with tracking SLO.
AB  - Fixational eye movements remain a major cause of artifacts in optical coherence
      tomography (OCT) images despite the increases in acquisition speeds. One approach
      to eliminate the eye motion is to stabilize the ophthalmic imaging system in real
      time. This paper describes and quantifies the performance of a tracking OCT
      system, which combines a phase-stabilized optical frequency domain imaging (OFDI)
      system and an eye tracking scanning laser ophthalmoscope (TSLO). We show that
      active eye tracking minimizes artifacts caused by eye drift and micro saccades.
      The remaining tracking lock failures caused by blinks and large saccades generate
      a trigger signal which signals the OCT system to rescan corrupted B-scans.
      Residual motion artifacts in the OCT B-scans are reduced to 0.32 minutes of arc
      (~1.6 um) in an in vivo human eye enabling acquisition of high quality images
      from the optic nerve head and lamina cribrosa pore structure.

PMID- 23162732
TI  - Standoff detection of biological agents using laser induced fluorescence-a
      comparison of 294 nm and 355 nm excitation wavelengths.
AB  - Standoff detection measuring the fluorescence spectra of seven different
      biological agents excited by 294 nm as well as 355 nm wavelength laser pulses has
      been undertaken. The biological warfare agent simulants were released in a semi
      closed aerosol chamber at 210 m standoff distance and excited by light at either
      of the two wavelengths using the same instrument. Significant differences in
      several of the agents' fluorescence response were seen at the two wavelengths.
      The anthrax simulants' fluorescence responses were almost an order of magnitude
      stronger at the shorter wavelength excitation. However, most importantly, the
      fluorescence spectra were significantly more dissimilar at 294 nm than at 355 nm
      excitation with ~7 nm spectral resolution. This indicates that classification of
      the substances should be possible with a lower error rate for standoff detection
      using 294 nm rather than 355 nm excitation wavelength, or even better, utilizing
      both.

PMID- 23162733
TI  - Optical microangiography of retina and choroid and measurement of total retinal
      blood flow in mice.
AB  - We present a novel application of optical microangiography (OMAG) imaging
      technique for visualization of depth-resolved vascular network within retina and
      choroid as well as measurement of total retinal blood flow in mice. A fast speed
      spectral domain OCT imaging system at 820nm with a line scan rate of 140 kHz was
      developed to image the posterior segment of eyes in mice. By applying an OMAG
      algorithm to extract the moving blood flow signals out of the background tissue,
      we are able to provide true capillary level imaging of the retinal and choroidal
      vasculature. The microvascular patterns within different retinal layers are
      presented. An en face Doppler OCT approach [Srinivasan et al., Opt Express 18,
      2477 (2010)] was adopted for retinal blood flow measurement. The flow is
      calculated by integrating the axial blood flow velocity over the vessel area
      measured in an en face plane without knowing the blood vessel angle. Total
      retinal blood flow can be measured from both retinal arteries and veins. The
      results indicate that OMAG has the potential for qualitative and quantitative
      evaluation of the microcirculation in posterior eye compartments in mouse models
      of retinopathy and neovascularization.

PMID- 23162734
TI  - High-speed polarization sensitive optical coherence tomography scan engine based
      on Fourier domain mode locked laser.
AB  - We report on a new swept source polarization sensitive optical coherence
      tomography scan engine that is based on polarization maintaining (PM) fiber
      technology. The light source is a Fourier domain mode locked laser with a PM
      cavity that operates in the 1300 nm wavelength regime. It is equipped with a PM
      buffer stage that doubles the fundamental sweep frequency of 54.5 kHz. The
      fiberization allows coupling of the scan engine to different delivery probes. In
      a first demonstration, we use the system for imaging human skin at an A-scan rate
      of 109 kHz. The system illuminates the sample with circularly polarized light and
      measures reflectivity, retardation, optic axis orientation, and Stokes vectors
      simultaneously. Furthermore, depolarization can be quantified by calculating the
      degree of polarization uniformity (DOPU). The high scanning speed of the system
      enables dense sampling in both, the x- and y-direction, which provides the
      opportunity to use 3D evaluation windows for DOPU calculation. This improves the
      spatial resolution of DOPU images considerably.

PMID- 23162735
TI  - Radiance detection of non-scattering inclusions in turbid media.
AB  - Detection of non-scattering domains (voids) is an area of active research in
      biomedical optics. To avoid complexities of image reconstruction algorithms and
      requirements of a priori knowledge of void locations inherent to diffuse optical
      tomography (DOT), it would be useful to establish specific experimental
      signatures of voids that would help identify and detect them by other means. To
      address this, we present a radiance-based spectro-angular mapping approach that
      identifies void locations in the angular domain and establishes their spectral
      features. Using water-filled capillaries in scattering Intralipid as a test
      platform, we demonstrate perturbations in the directional photon density
      distribution produced by individual voids.

PMID- 23162736
TI  - Noninvasive glucose detection in human skin using wavelength modulated
      differential laser photothermal radiometry.
AB  - Noninvasive glucose monitoring will greatly improve diabetes management. We
      applied Wavelength-Modulated Differential Laser Photothermal Radiometry (WM-DPTR)
      to noninvasive glucose measurements in human skin in vitro in the mid-infrared
      range. Glucose measurements in human blood serum diffused into a human skin
      sample (1 mm thickness from abdomen) in the physiological range (21-400 mg/dl)
      demonstrated high sensitivity and accuracy to meet wide clinical detection
      requirements. It was found that the glucose sensitivity could be tuned by
      adjusting the intensity ratio and phase difference of the two laser beams in the
      WM-DPTR system. The measurement results demonstrated the feasibility of the
      development of WM-DPTR into a clinically viable noninvasive glucose biosensor.

PMID- 23162737
TI  - 4D shear stress maps of the developing heart using Doppler optical coherence
      tomography.
AB  - Accurate imaging and measurement of hemodynamic forces is vital for investigating
      how physical forces acting on the embryonic heart are transduced and influence
      developmental pathways. Of particular importance is blood flow-induced shear
      stress, which influences gene expression by endothelial cells and potentially
      leads to congenital heart defects through abnormal heart looping, septation, and
      valvulogenesis. However no imaging tool has been available to measure shear
      stress on the endocardium volumetrically and dynamically. Using 4D structural and
      Doppler OCT imaging, we are able to accurately measure the blood flow in the
      heart tube in vivo and to map endocardial shear stress throughout the heart cycle
      under physiological conditions for the first time. These measurements of the
      shear stress patterns will enable precise titration of experimental perturbations
      and accurate correlation of shear with the expression of molecules critical to
      heart development.

PMID- 23162739
TI  - 3D structure analysis of PAKs: A clue to the rational design for affinity
      reagents and blockers.
AB  - The p21-activated kinase (PAK) family plays a versatile role in cell signaling by
      forming a hub of interactions. PAKs bind the GTPases like RAC and CDC42. Their
      proline-rich motifs bind SH3 adaptor proteins such as PIX and NCK. PAKs display
      nuclear localization signal sites and a potential Integrin binding site. No fully
      complete structure of the PAKs has been published; partial 3D structures of the
      PAK family kinases include portions of the auto-inhibited PAK1, GTPase bound to
      small peptides from PAKs, and the kinase domains from PAK1 and PAK4-6 (with small
      ligands in a few cases). This review focuses on exploring the intermolecular
      interaction regions in these 3D structures and we offer insights on the missing
      regions in crystal structure of the auto-inhibited PAK1. Understanding and
      modulation of PAK intermolecular interactions can pave the way for PAK blockers
      and biosensors.

PMID- 23162738
TI  - PAK family kinases: Physiological roles and regulation.
AB  - The p21-activated kinases (PAKs) are a family of Ser/Thr protein kinases that are
      represented by six genes in humans (PAK 1-6), and are found in all eukaryotes
      sequenced to date. Genetic and knockdown experiments in frogs, fish and mice
      indicate group I PAKs are widely expressed, required for multiple tissue
      development, and particularly important for immune and nervous system function in
      the adult. The group II PAKs (human PAKs 4-6) are more enigmatic, but their
      restriction to metazoans and presence at cell-cell junctions suggests these
      kinases emerged to regulate junctional signaling. Studies of protozoa and fungal
      PAKs show that they regulate cell shape and polarity through phosphorylation of
      multiple cytoskeletal proteins, including microtubule binding proteins, myosins
      and septins. This chapter discusses what we know about the regulation of PAKs and
      their physiological role in different model organisms, based primarily on gene
      knockout studies.

PMID- 23162740
TI  - Mouse models of PAK function.
AB  - p21-activated kinases are a family of highly conserved protein serine/threonine
      kinases that are increasingly recognized as playing essential roles in a variety
      of key signaling processes. Genetic analyses in mice, using constitutive or
      regulated gene disruption, have provided important new insights into PAK
      function. In this paper, we review the genetic analysis of all six PAK genes in
      mice. These data address the singular and redundant functions of the various PAK
      genes and suggest therapeutic possibilities for small molecule PAK inhibitors or
      activators.

PMID- 23162741
TI  - Novel roles of PAK1 in the heart.
AB  - Our work and others' over the past few years have led to the identification of
      new roles of PAK1 in cardiac physiology, such as the regulation of cardiac ion
      channel and actomyosin function. More recent studies have revealed that PAK1
      deficient mice were vulnerable to cardiac hypertrophy and readily progress to
      failure under sustained pressure overload and susceptible to ischemia/reperfusion
      injury. Our further study indicated that the PAK1 activator FTY720 was able to
      prevent this pressure overload-induced hypertrophy in wild-type mice without
      compromising their cardiac functions. A cardiac protective effect against
      ischemia/reperfusion injury by FTY720 was also observed in both rat and mouse
      models by us and others. Thus, these studies suggest that PAK1 is more important
      in the heart than previously thought, in particular a therapeutic potential of
      PAK1 activators. In the future, in-depth investigations are required to further
      substantiate our hypotheses on mechanisms for PAK1 function in the heart and to
      explore a therapeutic potential of FTY720 and other PAK1 activators in heart
      disease conditions.

PMID- 23162744
TI  - Recent advances in the development of p21-activated kinase inhibitors.
AB  - The p21-activated kinases (PAKs) are downstream effectors of the small G-proteins
      of the Rac and cdc42 family and have been implicated as essential for cell
      proliferation and survival. Recent studies have also demonstrated the promise of
      PAKs as therapeutic targets in various types of cancers. The PAKs are divided
      into two major groups (group I and II) based on sequence similarities. Although
      the different roles the PAK groups might play are not well understood, recent
      efforts have focused on the identification of kinase inhibitors that can
      discriminate between the two groups. In this review these efforts and newly
      identified inhibitors will be described and future directions discussed.

PMID- 23162742
TI  - PAK signaling in cancer.
AB  - Transformation of a normal cell to a cancer cell is caused by mutations in genes
      that regulate proliferation, apoptosis, and invasion. Small GTPases such as Ras,
      Rho, Rac and Cdc42 orchestrate many of the signals that are required for
      malignant transformation. The p21-activated kinases (PAKs) are effectors of Rac
      and Cdc42. PAKs are a family of serine/threonine protein kinases comprised of six
      isoforms (PAK1-6), and they play important roles in cytoskeletal dynamics, cell
      survival and proliferation. They act as key signal transducers in several cancer
      signaling pathways, including Ras, Raf, NFkappaB, Akt, Bad and p53. Although PAKs
      are not mutated in cancers, they are overexpressed, hyperactivated or amplified
      in several human tumors and their role in cell transformation make them
      attractive therapeutic targets. This review discusses the evidence that PAK is
      important for cell transformation and some key signaling pathways it regulates.
      This review primarily discusses Group I PAKs (PAK1, PAK2 and PAK3) as Group II
      PAKs (PAK4, PAK5 and PAK6) are discussed elsewhere in this issue (by Minden).

PMID- 23162743
TI  - PAK in Alzheimer disease, Huntington disease and X-linked mental retardation.
AB  - Developmental cognitive deficits including X-linked mental retardation (XLMR) can
      be caused by mutations in P21-activated kinase 3 (PAK3) that disrupt actin
      dynamics in dendritic spines. Neurodegenerative diseases such as Alzheimer
      disease (AD), where both PAK1 and PAK3 are dysregulated, may share final common
      pathways with XLMR. Independent of familial mutation, cognitive deficits emerging
      with aging, notably AD, begin after decades of normal function. This prolonged
      prodromal period involves the buildup of amyloid-beta (Abeta) extracellular
      plaques and intraneuronal neurofibrillary tangles (NFT). Subsequently region
      dependent deficits in synapses, dendritic spines and cognition coincide with
      dysregulation in PAK1 and PAK. Specifically proximal to decline, cytoplasmic
      levels of actin-regulating Rho GTPase and PAK1 kinase are decreased in moderate
      to severe AD, while aberrant activation and translocation of PAK1 appears around
      the onset of cognitive deficits. Downstream to PAK1, LIM kinase inactivates
      cofilin, contributing to cofilin pathology, while the activation of Rho-dependent
      kinase ROCK increases Abeta production. Abeta activation of fyn disrupts neuronal
      PAK1 and ROCK-mediated signaling, resulting in synaptic deficits. Reductions in
      PAK1 by the anti-amyloid compound curcumin suppress synaptotoxicity. Similarly
      other neurological disorders, including Huntington disease (HD) show
      dysregulation of PAKs. PAK1 modulates mutant huntingtin toxicity by enhancing
      huntingtin aggregation, and inhibition of PAK activity protects HD as well as
      fragile X syndrome (FXS) symptoms. Since PAK plays critical roles in learning and
      memory and is disrupted in many cognitive disorders, targeting PAK signaling in
      AD, HD and XLMR may be a novel common therapeutic target for AD, HD and XLMR.

PMID- 23162746
TI  - Immunological thought in the mainstream of cancer research: Past divorce, recent
      remarriage and elective affinities of the future.
AB  - Immunological thought is exerting a growing effect in cancer research, correcting
      a divorce that occurred in the mainstream of the field decades ago just as cancer
      genetics began to emerge as a dominant movement. Today, with a general consensus
      on the significance of epigenetics, the inflammatory cancer microenvironment and
      the immune response in determining cancer pathophysiology, a new synthesis of
      thought is being spurred by a remarriage with cancer immunology, with great
      implications for the future of the field. This perspective offers a view on how
      this synthesis is impacting both the understanding and treatment of cancer using
      adjuvant immunomodulatory modalities in the context of surgical, radiotherapeutic
      and chemotherapeutic interventions which are present standards of care. With the
      revolutions in immunochemotherapy and immunoradiotherapy coming this decade, the
      next great challenge faced by the field will be how to identify simple, cost
      effective and broadly applicable solutions that do not rely deeply on
      personalized characters, in an effort to minimize the daunting complexity and
      costs of a problem that challenges not only physicians and patients but also
      health care systems and insurers caring for aging populations in the developed
      world.

PMID- 23162747
TI  - Carcinoma origin dictates differential skewing of monocyte function.
AB  - Macrophages are versatile cells, which phenotype is profoundly influenced by
      their environment. Pro-inflammatory classically activated or M1 macrophages, and
      anti-inflammatory alternatively-activated or M2 macrophages represent two
      extremes of a continuum of functional states. Consequently, macrophages that are
      present in tumors can exert tumor-promoting and tumor-suppressing activity,
      depending on the tumor milieu. In this study we investigated how human monocytes
      the precursors of macrophages-are influenced by carcinoma cells of different
      origin. We demonstrate that monocytes, stimulated with breast cancer supernatant,
      showed increased expression of interleukin (IL)-10, IL-8 and chemokines CCL17 and
      CCL22, which are associated with an alternatively-activated phenotype. By
      contrast, monocytes that were cultured in supernatants of colon cancer cells
      produced more pro-inflammatory cytokines (e.g., IL-12 and TNFalpha) and reactive
      oxygen species. Secretome analysis revealed differential secretion of proteins by
      colon and breast cancer cell lines, of which the proteoglycan versican was
      exclusively secreted by colon carcinoma cell lines. Reducing active versican by
      blocking with monoclonal antibodies or shRNA diminished pro-inflammatory cytokine
      production by monocytes. Thus, colon carcinoma cells polarize monocytes toward a
      more classically-activated anti-tumorigenic phenotype, whereas breast carcinomas
      predispose monocytes toward an alternatively activated phenotype. Interestingly,
      presence of macrophages in breast or colon carcinomas correlates with poor or
      good prognosis in patients, respectively. The observed discrepancy in macrophage
      activation by either colon or breast carcinoma cells may therefore explain the
      dichotomy between patient prognosis and macrophage presence in these different
      tumors. Designing new therapies, directing development of monocytes toward M1
      activated tumor macrophages in cancer patients, may have great clinical benefits.

PMID- 23162748
TI  - Understanding key assay parameters that affect measurements of trastuzumab
      mediated ADCC against Her2 positive breast cancer cells.
AB  - Use of the antibody trastuzumab to kill HER2+ breast cancer cells is an
      attractive therapy because of its specificity and minimal adverse effects.
      However, a large fraction of HER2+ positive patients are or will become resistant
      to this treatment. No other markers are used to determine sensitivity to
      trastuzumab other than HER2 status.Using the xCELLigence platform and flow
      cytometry, we have compared the ability of mononuclear cells (MNCs) from normal
      and breast cancer patients to kill different breast cancer cell lines in the
      presence (i.e., ADCC) or absence of trastuzumab. Image analysis and cell
      separation procedures were used to determine the differential contribution of
      immune cell subsets to ADCC activity. The assay demonstrated that ADCC activity
      is dependent on the presence of trastuzumab, the level of HER2 expression on the
      target, and the ratio of MNCs to tumor cells. There is a wide range of ADCC
      activity among normal individuals and breast cancer patients for high and low
      HER2-expressing tumor targets. Fresh MNCs display higher ADCC levels compared
      with cryopreserved cells. Natural killer cells display the highest ADCC followed
      by monocytes. T cells and B cells were ineffective in killing. A major mechanism
      of killing of tumor cells involves insertion of granzyme B and caspase enzymes
      via the antibody attached MNCs.

PMID- 23162749
TI  - Vaccination with immunotherapeutic Listeria monocytogenes induces IL-17(+)
      gammadelta T cells in a murine model for HPV associated cancer.
AB  - Interleukin 17 (IL-17) is produced during infection with Listeria monocytogenes
      and is also an important regulator of tumor development with both pro- and anti
      tumorigenic effects. alphabeta T cells and gammadelta T cells are among the
      principle producers of IL-17 in response to infection and other proinflammatory
      conditions. Listeria-based cancer immunotherapies induce IFNgamma directed Th1
      dependent tumor regression; however, the role of IL-17 in Listeria based
      immunotherapy has not been addressed. Therefore, we investigated the ability of
      attenuated Listeria-based immunotherapy to induce IL-17 producing cells in a
      model of cervical cancer and the potential impact that these cells have on anti
      tumor vaccine efficacy. Here we show that vaccination of tumor bearing mice with
      Listeria vaccines resulted in elevated levels of intratumoral IL-17 and increased
      IL-17 production by gammadelta TCR+ cells, exclusively. IL-17 producing cells
      were lacking in tumors of gammadelta T-cell-deficient mice; however, the absence
      of gammadelta T cells, including IL-17+ gammadelta T cells, did not alter tumor
      progression or abrogate the efficacy of the Listeria-based vaccine indicating
      that alphabeta T cells are key for clearance of the tumor. Th1 responses, known
      to be responsible for anti-tumor Listeria-based vaccine efficacy, appear to be
      sufficient for tumor regression in gammadelta T-cell-deficient mice. We conclude
      that the efficacy of Listeria-based vaccine does not rely on gammadelta T cells
      (or IL-17 produced by them) in a TC.1 tumor model; however, Listeria-based
      immunotherapy can be used to induce IL-17+ gammadelta T cells that are important
      for regression observed in alternative cancer models.

PMID- 23162750
TI  - High endothelial venules (HEVs) in human melanoma lesions: Major gateways for
      tumor-infiltrating lymphocytes.
AB  - The presence of tumor-infiltrating lymphocytes (TILs) is a strong prognostic
      parameter for local dissemination and overall survival in melanoma. Lymphocyte
      migration from blood into peripheral tissues is mainly regulated by vascular
      endothelium. However, the blood vessels and mechanisms governing the recruitment
      of TILs in melanoma tumors remain poorly understood. Here, we show that high
      endothelial venules (HEVs), specialized blood vessels for lymphocyte
      extravasation into lymphoid tissues, are frequently found in melanoma tumors and
      are associated with high levels of lymphocyte infiltration. The analysis of 225
      primary melanomas revealed that lymphocytes specifically infiltrated HEV-rich
      areas of melanoma tumors and that the density of MECA-79+ HEVs was variable among
      patients and strongly correlated with CD3+, CD8+ and CD20+ TIL densities.
      Inflammatory (CCL5, CXCL9, CXCL10 and CXCL11) and lymphoid (CCL21, CCL19 and
      CXCL13) chemokines as well as TH1 and naive T-cell genes were overexpressed in
      melanoma samples with high densities of tumor HEVs. Mature dendritic cells (mDCs)
      were frequently found around tumor HEVs and densities of HEVs and DC-LAMP+ mDCs
      within tumor stroma were strongly correlated. DCs which maintain HEVs in lymph
      nodes, may thus also contribute to the regulation of HEVs in melanomas. Finally,
      we found significantly higher densities of tumor HEVs in melanomas with tumor
      regression, low Clark level of invasion and thin Breslow thickness (all p <
      0.001). The strong association between tumor HEVs, TILs, mDCs and clinical
      parameters of melanoma, supports a critical role for HEVs in limiting malignant
      melanoma development through both naive and effector T-lymphocyte recruitment and
      activation.

PMID- 23162752
TI  - AAV2/IL-12 gene delivery into dendritic cells (DC) enhances CTL stimulation above
      other IL-12 applications: Evidence for IL-12 intracrine activity in DC.
AB  - Adoptive transfer of antigen-specific cytotoxic T lymphocytes (CTL) holds
      significant promise in treating cancer and Th1 response cytokines are critical
      for their stimulation. Recently we reported that interleukin 7-(IL-7) and
      interferongamma-(IFNgamma) autocrine/T cell gene delivery resulted in superior ex
      vivo CTL stimulation over paracrine/DC delivery. IL-12 is yet another important
      Th1 cytokine which affects both DC and T cells. Here, using adeno-associated
      virus Type 2 (AAV2) gene delivery, IL-12-paracrine/DC gene delivery gave
      significantly superior stimulation of carcinoembryonic antigen (CEA)-specific CTL
      killing over that induced by autocrine gene delivery (or exogenous IL-12
      addition). This is surprising as both AAV2/IL-12-treated T cells and DC secreted
      approximately the same level of IL-12. Paracrine IL-12 gene delivery also
      resulted in highest IL-12/IL-10 secretion ratio by DC and highest CD40, CD80,
      CD83 and CD86 expression. Moreover, AAV2/IL-12-DC stimulated the highest T-cell
      IFNgamma production, highest T cell proliferation, highest CD69+/CD8+ levels, and
      lowest level of CD25+/CD4+ Treg. These data strongly suggest that the primary
      activity of IL-12 during CTL generation is upon the DC. These data are also
      consistent with there being novel activity for IL-12 within the DC itself, not
      involving its surface receptor; an "intracrine" activity. Given the plethora of
      IL-12 studies, these data also suggest that this gene delivery comparison
      approach could be useful for uncovering new cytokine activities and mechanism(s)
      of action gone unrecognized by conventional immunologic assays. Finally, these
      data further suggest AAV2/IL-12 intracrine gene delivery into DC may have utility
      in immunotherapy protocols involving antigen-specific CTL.

PMID- 23162751
TI  - Tumor cells, rather than dendritic cells, deliver antigen to the lymph node for
      cross-presentation.
AB  - It is widely accepted that generation of tumor specific CD8+ T-cell responses
      occur via cross-priming; however the source of tumor antigen for this event is
      unknown. We examined the source and form of tumor antigen required for cross
      presentation in the local lymph node (LN) using a syngeneic mouse tumor model
      expressing a marker antigen. We found that cross-presentation of this model tumor
      antigen in the LN is dependent on continuous traffic of antigen from the tumor
      site, but without any detectable migration of tumor resident dendritic cells
      (DCs). Instead, small numbers of tumor cells metastasize to local LNs where they
      are exposed to a localized CTL attack, resulting in delivery of tumor antigen
      into the cross-presentation pathway.

PMID- 23162753
TI  - An ENU mutagenesis approach to dissect "self"-induced immune responses: 
      Unraveling the genetic footprint of immunosurveillance.
AB  - The immune system exerts a critical function as it recognizes and eliminates
      transformed or neoplastic cells, a process also referred to as
      immunosurveillance. NK cells play a particularly important role in that they are
      able to recognize tumor cells via "missing-self"-i.e., the absence of major
      histocompatibility complex Class I on target cells. Moreover, recent studies
      suggest that NK cells also participate in the onset and regulation of adaptive
      immune responses. The exact molecular pathways by which this occurs, however,
      remain poorly understood. To obtain further insight into the genes that are
      required for self-induced immune responses via NK cell-mediated cell death, our
      laboratory initiated a forward genetic approach using N-ethyl-N-nitrosourea (ENU)
      as a mutagen. Specifically, we tested the ability of NK cells from G3 ENU
      germline mice to recognize missing-self target cells and induce CD8+ T-cell
      responses following immunization with irradiated tumor cells. Here we present two
      ENU germline mutants, designated Ace and Chip, that are defective in the
      recognition of beta-2 microglobulin-deficient target cells, yet exhibit improved
      clearance of B16 melanoma cells in vivo. Coarse mapping and whole genome
      sequencing of the Chip mutation revealed a missense mutation causing a T'A amino
      acid substitution in the highly conserved third immuno-receptor tyrosine-based
      switch motif of CD244 (2B4). The forward genetic approach described here promises
      to reveal important insight into critical genes that are required for host
      responses involved in anticancer immunity.

PMID- 23162754
TI  - A sensitivity scale for targeting T cells with chimeric antigen receptors (CARs)
      and bispecific T-cell Engagers (BiTEs).
AB  - Although T cells can mediate potent antitumor responses, immune tolerance
      mechanisms often result in the deletion or inactivation of T cells that express T
      cell receptors (TCRs) against potentially effective target epitopes. Various
      approaches have been devised to circumvent this problem. In one approach, the
      gene encoding an antibody against a cancer-associated antigen is linked, in the
      form of a single-chain variable fragment (scFv), to genes that encode
      transmembrane and signaling domains. This chimeric antigen receptor (CAR) is then
      introduced into T cells for adoptive T-cell therapy. In another approach, the
      anti-cancer scFv is fused to a scFv that binds to the CD3epsilon subunit of the
      TCR/CD3 complex. This fusion protein serves as a soluble, injectable product that
      has recently been termed bispecific T-cell engager (BiTE). Both strategies have
      now been tested in clinical trials with promising results, but the comparative
      efficacies are not known. Here, we performed a direct comparison of the in vitro
      sensitivity of each strategy, using the same anti-cancer scFv fragments, directed
      against a tumor-specific glycopeptide epitope on the sialomucin-like
      transmembrane glycoprotein OTS8, which results form a cancer-specific mutation of
      Cosmc. While both approaches showed specific responses to the epitope as revealed
      by T cell-mediated cytokine release and target cell lysis, CAR-targeted T cells
      were more sensitive than BiTE-targeted T cells to low numbers of antigens per
      cell. The sensitivity scale described here provides a guide to the potential use
      of these two different approaches.

PMID- 23162755
TI  - Viral antigen mediated NKp46 activation of NK cells results in tumor rejection
      via NK-DC crosstalk.
AB  - Natural killer (NK) cells play a critical role in antitumor immunity, their
      activation being regulated through NK cell receptors. Although the endogenous
      ligands for these receptors are largely unknown, viral ligands have been
      identified. We investigated the ability of an activating NK receptor ligand
      derived from the mumps virus, haemagglutinin-neuraminidase (HN) to enhance NK
      activation against tumor cells. HN-expressing B16.OVA tumor cells induced
      stronger activation of NK cells compared with B16.OVA cells and also promoted
      dendritic cell (DC) activation toward a DC1 phenotype, in vitro. Moreover,
      incubation of DCs, NK cells and HN-expressing B16-OVA cells further enhanced NK
      cell activation through the NK-DC crosstalk, in a cell-to-cell contact- and IL-12
      dependent fashion. Immunization of mice with HN-expressing B16-OVA cells resulted
      in > 85% survival rate after subsequent challenge with parental B16 or B16.OVA
      tumor cells. Tumor rejection was dependent on both NK and CD8+ T cells but not on
      CD4+ T cells, demonstrating induction of an effective adaptive immune response
      through innate immune cell activation. Our data indicate the potential of using
      robust NK cell activation, which through the NK-DC crosstalk stimulates effective
      antitumor responses, providing an alternate vaccine strategy.

PMID- 23162756
TI  - Immunotherapy against the radial glia marker GLAST effectively triggers specific
      antitumor effectors without autoimmunity.
AB  - The glutamate-aspartate transporter GLAST is a radial glia marker that is highly
      expressed in GL261 stem-like cells (GSCs). To target GLAST, we treated glioma
      bearing mice with three subcutaneous injections of four GLAST peptides emulsified
      with Montanide ISA-51 in association with granulocyte macrophage colony
      stimulating factor (GM-CSF) injections. Vaccination with GLAST peptides
      significantly prolonged survival, effectively enhanced systemic T-cell and NK
      cell responses and promoted robust antitumor cytotoxicity. GLAST expression
      significantly decreased in gliomas from immunized mice, as evaluated by
      histological analysis and real-time PCR (RT-PCR). Moreover, the immunization
      protocol led to the upregulation of interferongamma (IFNgamma) and tumor necrosis
      factoralpha (TNFalpha) as well as to the downregulation of transforming growth
      factor (TGF) beta1 and beta2 in the tumor. Beyond these changes, gliomas from
      immunized mice exhibited an increased recruitment of NK cells and antigen
      specific CD8+ T cells expressing the tumor homing molecule VLA-4, as well as a
      local chemotactic gradient featuring expression of CXCL10 (which may be
      responsible for the recruitment of CTLs), CCL3, CCL4 and CCL5 (which are involved
      in NK-cell migration), and NKG2D ligand on glioma cells. Importantly, although
      GLAST is expressed in the central nervous system, autoimmune reactions were not
      observed in immunized mice. Altogether, these results support the contention that
      GLAST may constitute a glioma antigen against which immune responses can be
      efficiently induced without major safety concerns.

PMID- 23162758
TI  - Targeting the MHC Class II antigen presentation pathway in cancer immunotherapy.
AB  - The success of immunotherapy relies on the participation of all arms of the
      immune system and the role of CD4+ T lymphocytes in preventing tumor growth is
      now well established. Understanding how tumors evade immune responses holds the
      key to the development of cancer immunotherapies. In this review, we discuss how
      MHC Class II expression varies in cancer cells and how this influences antitumor
      immune responses. We also discuss the means that are currently available for
      harnessing the MHC Class II antigen presentation pathway for the development of
      efficient vaccines to activate the immune system against cancer.

PMID- 23162759
TI  - TLR3/TICAM-1 signaling in tumor cell RIP3-dependent necroptosis.
AB  - The engagement of Toll-like receptor 3 (TLR3) leads to the oligomerization of the
      adaptor TICAM-1 (TRIF), which can induces either of three acute cellular
      responses, namely, cell survival coupled to Type I interferon production, or cell
      death, via apoptosis or necrosis. The specific response elicited by TLR3
      determines the fate of affected cells, although the switching mechanism between
      the two cell death pathways in TLR3-stimulated cells remains molecularly unknown.
      Tumor necrosis factor alpha (TNFalpha)-mediated cell death can proceed via
      apoptosis or via a non-apoptotic pathway, termed necroptosis or programmed
      necrosis, which have been described in detail. Interestingly, death domain
      containing kinases called receptor-interacting protein kinases (RIPs) are
      involved in the signaling pathways leading to these two cell death pathways.
      Formation of the RIP1/RIP3 complex (called necrosome) in the absence of caspase 8
      activity is crucial for the induction of necroptosis in response to TNFalpha
      signaling. On the other hand, RIP1 is known to interact with the C-terminal
      domain of TICAM-1 and to modulate TLR3 signaling. In macrophages and perhaps
      tumor cell lines, RIP1/RIP3-mediated necroptotic cell death can ensue the
      administration of the TLR agonist polyI:C. If this involved the TLR3/TICAM-1
      pathway, the innate sensing of viral dsRNA would be linked to cytopathic effects
      and to persistent inflammation, in turn favoring the release of damage-associated
      molecular patterns (DAMPs) in the microenvironment. Here, we review accumulating
      evidence pointing to the involvement of the TLR3/TICAM-1 axis in tumor cell
      necroptosis and the subsequent release of DAMPs.

PMID- 23162760
TI  - A perspective on new immune adjuvant principles: Reprogramming inflammatory
      states to permit clearance of cancer cells and other age-associated cellular
      pathologies.
AB  - Aging entails the accumulation of neoantigens comprised of aggregated, oxidized,
      mutated and misfolded biomolecules, including advanced-glycation end projects
      (AGEs). There is evidence that the immune system can recognize and clear cells
      fouled by these molecular debris, which contribute to the emergence of cancer and
      other major age-associated diseases such as atherogenic and neurodegenerative
      disorders. However, this process may become increasingly inefficient with aging,
      perhaps in part because of an insufficiency of adjuvant signals normally
      associated with infection that can program productive inflammatory states and
      properly orient the immune system toward regenerative healing. Here we propose
      conceptual foundations for exploring a small set of infection-associated
      molecules as potential immune adjuvants to reprogram non-productive inflammatory
      states in aging tissues, and to improve the clearance of cellular pathologies
      that engender age-associated disease. The proposed adjuvant classes include a
      subset of D-amino acids used by bacteria to disrupt biofilms; nucleoside
      derivatives of N6-methyladenine, which functions at the core of bacterial dam
      restriction systems; and derivatives of the galactosyl trisaccharide alpha-Gal,
      which invokes the hyperacute response in primates. These foreign amino acids,
      nucleosides and sugar molecules are generally rare or absent in humans, except in
      association with infections by bacteria, protists or nematodes. A rationale for
      exploration of these candidate adjuvant principles and their chemical derivatives
      is discussed in terms of their use in generalized strategies to improve the
      prevention or treatment of cancer and other age-associated diseases, as negative
      modifiers of aging.

PMID- 23162762
TI  - The antigen specific composition of melanoma tumor infiltrating lymphocytes?
AB  - Large numbers of tumor associated antigens has been characterized, but only a
      minor fraction of these are recognized by tumor infiltrating lymphocytes of
      melanoma, although these have shown the ability to recognize tumor and provide
      tumor regression upon adoptive transfer. Thus the peptide recognition of the
      majority of the CD8 tumor infiltrating lymphocytes remains to be identified.

PMID- 23162761
TI  - The early antitumor immune response is necessary for tumor growth: Re-visiting
      Prehn's hypothesis in the human melanoma system.
AB  - Early events responsible of tumor growth in patients with a normal immune system
      are poorly understood. Here, we discuss, in the context of human melanoma, the
      Prehn hypothesis according to which a weak antitumor immune response may be
      required for tumor growth before weakly or non-immunogenic tumor cell
      subpopulations are selected by the immune system.

PMID- 23162763
TI  - Distinct anti-tumoral functions of adaptive immune cells in liver cancer.
AB  - Hepatocellular carcinoma (HCC) commonly arises in chronically inflamed livers,
      but may also provoke (anti-tumoral) immune responses. Using non-inflammatory
      diethylnitrosamine (DEN)-induced liver cancer in mice, we demonstrate that
      distinct axes of the adaptive immune system, which are also prognostic in human
      HCC, actively suppress hepatocarcinogenesis by controlling tumor formation and
      progression.

PMID- 23162757
TI  - Trial watch:  FDA-approved Toll-like receptor agonists for cancer therapy.
AB  - Toll-like receptors (TLRs) have first been characterized for their capacity to
      detect conserved microbial components like lipopolysaccharide (LPS) and double
      stranded RNA, resulting in the elicitation of potent (innate) immune responses
      against invading pathogens. More recently, TLRs have also been shown to promote
      the activation of the cognate immune system against cancer cells. Today, only
      three TLR agonists are approved by FDA for use in humans: the bacillus Calmette
      Guerin (BCG), monophosphoryl lipid A (MPL) and imiquimod. BCG (an attenuated
      strain of Mycobacterium bovis) is mainly used as a vaccine against tuberculosis,
      but also for the immunotherapy of in situ bladder carcinoma. MPL (derived from
      the LPS of Salmonella minnesota) is included in the formulation of Cervarix(r), a
      vaccine against human papillomavirus-16 and -18. Imiquimod (a synthetic
      imidazoquinoline) is routinely employed for actinic keratosis, superficial basal
      cell carcinoma, and external genital warts (condylomata acuminata). In this Trial
      Watch, we will summarize the results of recently completed clinical trials and
      discuss the progress of ongoing studies that have evaluated/are evaluating FDA
      approved TLR agonists as off-label medications for cancer therapy.

PMID- 23162764
TI  - "Flagellated" cancer cells propel anti-tumor immunity.
AB  - The use of innate immune receptor agonists in cancer therapies has suffered from
      many drawbacks. Our recent observations suggest that some of these hurdles can be
      overcome by introducing flagellin into tumor cells to promote tumor antigen
      presentation by dendritic cells (DCs) and simultaneously trigger two types of
      pattern recognition receptors (PRRs).

PMID- 23162765
TI  - Translating the combination of TGFbeta blockade and radiotherapy into clinical
      development in glioblastoma.
AB  - To improve multimodal glioblastoma treatment strategies, it appears useful to
      integrate a selective inhibitor of the TbetaR-I kinase, which may be able to
      potentiate radiation responses by increasing apoptosis and cancer-stem-like cell
      targeting while blocking DNA damage repair, invasion, mesenchymal transition and
      angiogenesis.1.

PMID- 23162766
TI  - Tumor suppressor ARF: The new player of innate immunity.
AB  - ARF (alternative reading frame) is one of the most important tumor regulator
      playing critical roles in controlling tumor initiation and progression. Recently,
      we have demonstrated a novel and unexpected role for ARF as modulator of
      inflammatory responses.

PMID- 23162767
TI  - Class I histone deacetylase inhibition is a novel mechanism to target regulatory
      T cells in immunotherapy.
AB  - Regulatory T cells (Tregs) represent a major obstacle of cancer immunotherapy. We
      reviewed here our discovery that Class I histone deacetylase (HDAC) inhibition
      can functionally target Tregs and help break the immune tolerance. We also
      discuss the effects of different classes of HDAC inhibitors on Tregs and the
      underline mechanisms, which may have a direct impact on designing cancer
      immunotherapy trials involving HDAC inhibitors.

PMID- 23162768
TI  - How two sites of inflammation promote carcinogenesis: The role of macrophages in
      inflammation associated carcinogenesis.
AB  - We recently reported that anti-inflammatory macrophages contribute to the
      initiation of colorectal carcinogenesis in IBD patients by inducing epithelial
      mesenchymal-transition associated alterations in colonic epithelial cells. In
      this process, TGFbeta1 dependent upregulation of the adhesion molecule L1CAM is
      one key event, paving the way to colitis associated tumorigenesis and metastatic
      spread.

PMID- 23162769
TI  - New insights on the role of CD8(+)CD57(+) T-cells in cancer.
AB  - Incomplete differentiation of CD8+ cytotoxic T-lymphocytes (CTLs) in the tumor
      microenvironment is associated with cancer progression. We describe a new type of
      tumor-infiltrating CD8+CD57+ T cell in cancer with hybrid phenotypic and
      functional properties of both an early effector-memory cell and a terminally
      differentiated effector cell. These cells behave as incompletely-differentiated
      CTLs.

PMID- 23162770
TI  - Boosting antibody-dependant cellular cytotoxicity against tumor cells with a
      CD137 stimulatory antibody.
AB  - Monoclonal antibodies (mAb) induce tumor regression through antibody-dependant
      cellular cytotoxicity (ADCC). We recently showed that an agonistic anti-CD137 mAb
      stimulates natural killer (NK) cells which have been activated by a tumor
      specific mAb, resulting in increased ADCC against cancer cells.

PMID- 23162771
TI  - Monoclonal antibody (mAb)-based cancer therapy: Is it time to reevaluate dosing
      strategies?
AB  - Compelling evidence indicates Type I CD20 immunotherapeutic mAbs promote targeted
      tumor cell elimination exclusively via immune effector functions, which can be
      exhausted/saturated. mAb dosing paradigms should therefore take into account the
      capacity of these cytotoxic mechanisms, leading to the conclusion that lower
      doses, given frequently, may be far more effective.

PMID- 23162772
TI  - DNA methylation markers for breast cancer prognosis: Unmasking the immune
      component.
AB  - Currently, most of the prognostic and predictive gene expression signatures
      emerging for breast cancer concern the tumor component. In Dedeurwaerder et al.
      we show that DNA methylation profiling of breast tumors is a particularly
      sensitive means of capturing features of the immune component of breast tumors.
      Most importantly, correlation is observed between T-cell marker genes and breast
      cancer clinical outcome.

PMID- 23162773
TI  - The role of SMAC mimetics in regulation of tumor cell death and immunity.
AB  - Mimetics of second mitochondria-derived activator of caspases (SMAC) enhance
      tumor cell death in a variety of cancers. Several molecular mechanisms of action
      have been identified. However, it was only recently that the modus of action was
      linked to stimulation of anti-tumor immunity. Here we comment on these findings,
      highlighting several remaining questions.

PMID- 23162774
TI  - Good things come in small packages: Therapeutic anti-tumor immunity induced by
      microRNA nanoparticles.
AB  - Current ovarian cancer treatments based on surgery/chemotherapy show limited
      efficacy. Targeting immunosuppression is a requirement for the effectiveness of
      novel promising anti-tumor immunotherapies. Our latest work in preclinical models
      shows that nanoparticle-mediated delivery of immunostimulatory microRNAs
      specifically to tumor-associated leukocytes is sufficient to re-program
      immunological control of metastatic ovarian cancers.

PMID- 23162775
TI  - The role of tumor expression of CD200 in tumor formation, metastasis and
      susceptibility to T lymphocyte adoptive transfer therapy.
AB  - CD200 is a cell surface glycoprotein that has been implicated in a variety of
      human cancer cells and has been thought to play a pro-tumor role. However, in our
      recent study we have revealed that CD200 on cancer cells inhibits tumor formation
      and metastasis through inhibition of myeloid cells.

PMID- 23162776
TI  - How melanoma cells inactivate NK cells.
AB  - NK cells are the most potent effectors against different tumors in vitro.
      However, their efficacy in vivo is compromised by suppressive signals delivered
      by tumor or tumor-associated cells. This study unravels the molecular mechanisms
      by which melanomas disarm NK cells and offers clues to revert such inhibitory
      effect.

PMID- 23162777
TI  - Autophagy-assisted antigen cross-presentation: Autophagosome as the argo of
      shared tumor-specific antigens and DAMPs.
AB  - It is generally believed that most tumor antigens are passively released from
      either health or dying tumor cells as intact soluble antigens, peptide fragments
      complexed with heat shock proteins (HSPs), or packaged in secretary vesicles in
      the form of microparticles or exosomes. The passive release of tumor antigens is
      generally non-inflammatory and non-immunogenic; however, results from others and
      our laboratories suggest that autophagy is critically involved in immunogenic
      cell death.

PMID- 23162778
TI  - Oncolytic adenoviruses: A potent form of tumor immunovirotherapy.
AB  - The therapeutic efficacy of oncolytic viruses including adenovirus has been
      thought to depend mostly on direct viral destruction of tumor cells. However,
      this view has changed with the discovery that oncolysis can also induce innate
      and antigen-specific adaptive immunity against the tumor. Here we summarize our
      findings from cancer patients.

PMID- 23162779
TI  - Radiochemotherapy fosters a favorable pattern of inflammatory cells in head and
      neck tumors.
AB  - The immune milieu in malignant tumors can influence the prognosis of patients.
      However, little is known about the effect the antitumoral therapy has on the
      inflammatory infiltrate. In head and neck squamous cell carcinoma we found
      evidence that a neoadjuvant radiochemotherapy could modulate the composition of
      the intratumoral inflammation into an anti-tumoral pattern.

PMID- 23162780
TI  - A novel strategy for modulation of MDSC to enhance cancer immunotherapy.
AB  - Myeloid derived suppressor cells (MDSC) suppress anti-tumor immune responses. Our
      recent publication provides evidence that SHIP-1 plays a prominent role in
      pancreatic tumor development by regulating MDSC. Therefore, SHIP-1 may be a
      potential therapeutic target for the treatment of MDSC-related hematological
      malignancies and solid tumors.

PMID- 23162781
TI  - Won't you come on in? How to favor lymphocyte infiltration in tumors.
AB  - Abnormal tumor vasculature and endothelial cell anergy limit tumor/T-cell
      interactions. We have found that NGR-TNF, a tumor vasculature-homing derivative
      of TNF, selectively activates endothelial cells in neoplastic tissues and induces
      the release of chemokines that favor tumor infiltration by T cells, thereby
      enhancing the efficacy of active and adoptive immunotherapy.

PMID- 23162782
TI  - Turning the tumor microenvironment into a self vaccine site.
AB  - We aimed to determine if the tumor microenvironment could be turned into a "self"
      vaccine site. We show that provoking a local inflammatory response modulates
      endothelia to permit the infiltration of innate and adaptive effector cells which
      collaborate to eradicate the inflamed tumor and other tumor deposits, and provide
      long-term protection.

PMID- 23162783
TI  - Within tumors, interactions between T cells and tumor cells are impeded by the
      extracellular matrix.
AB  - In principle, T cells can recognize and kill cancer cells. However, tumors have
      the ability to escape T cell attack. By imaging the dynamic behavior of T cells
      in human lung tumor explants, we have recently established the importance of the
      extracellular matrix in limiting access of T cells to tumor cells.

PMID- 23162784
TI  - Sound efficacy of prophylactic HPV vaccination: Basics and implications.
AB  - Prophylactic human papillomavirus vaccine efficacy is almost too good to be true.
      The benefits of herd immunity will, however, not be gained without high vaccine
      coverage. Here the authors of two recent papers on HPV16/18 vaccine efficacy
      elaborate on the basics and implications of this approach for infection and
      cancer prevention.

PMID- 23162785
TI  - TAMable tumor-associated macrophages in response to innate RNA sensing.
AB  - Antitumor effect of PolyI:C (a viral dsRNA analog) has been attributed to
      dendritic cell (DC)-maturation activity, that drives antitumor NK cells, DC cross
      presentation, cytotoxic T lymphocytes and many IFN-inducible genes. According to
      a recent paper, tumor-infiltrating M2 macrophages are found to become an
      additional antitumor effector through polyI:C response.

PMID- 23162786
TI  - The Hypothalamic-Pituitary-Adrenal Axis, Obesity, and Chronic Stress Exposure:
      Sleep and the HPA Axis in Obesity.
AB  - Obesity, exposure to stress and inadequate sleep are prevalent phenomena in
      modern society. In this review we focus on their relationships and critically
      evaluate causality. In obese individuals, one of the main stress systems, the
      hypothalamic-pituitary-adrenal axis, is altered, and concentrations of cortisol
      are elevated in adipose tissue due to elevated local activity of 11beta
      hydroxysteroid dehydrogenase (HSD) type 1. Short sleep and decreased sleep
      quality are also associated with obesity. In addition, experimental sleep
      curtailment induces HPA-axis alterations which, in turn, may negatively affect
      sleep. These findings implicate that obesity, stress and sleep loss are all
      related in a vicious circle. Finally, we discuss new strategies to combat obesity
      through modulating cortisol levels in adipose tissue by 11beta-HSD(1) inhibitors
      or by improving sleep duration.

PMID- 23162788
TI  - A cross-race effect in metamemory: Predictions of face recognition are more
      accurate for members of our own race.
AB  - The Cross-Race Effect (CRE) in face recognition is the well-replicated finding
      that people are better at recognizing faces from their own race, relative to
      other races. The CRE reveals systematic limitations on eyewitness identification
      accuracy and suggests that some caution is warranted in evaluating cross-race
      identification. The CRE is a problem because jurors value eyewitness
      identification highly in verdict decisions. In the present paper, we explore how
      accurate people are in predicting their ability to recognize own-race and other
      race faces. Caucasian and Asian participants viewed photographs of Caucasian and
      Asian faces, and made immediate judgments of learning during study. An old/new
      recognition test replicated the CRE: both groups displayed superior
      discriminability of own-race faces, relative to other-race faces. Importantly,
      relative metamnemonic accuracy was also greater for own-race faces, indicating
      that the accuracy of predictions about face recognition is influenced by race.
      This result indicates another source of concern when eliciting or evaluating
      eyewitness identification: people are less accurate in judging whether they will
      or will not recognize a face when that face is of a different race than they are.
      This new result suggests that a witness's claim of being likely to recognize a
      suspect from a lineup should be interpreted with caution when the suspect is of a
      different race than the witness.

PMID- 23162787
TI  - Cannabinoids and value-based decision making: implications for neurodegenerative
      disorders.
AB  - In recent years, disturbances in cognitive function have been increasingly
      recognized as important symptomatic phenomena in neurodegenerative diseases,
      including Parkinson's Disease (PD). Value-based decision making in particular is
      an important executive cognitive function that is not only impaired in patients
      with PD, but also shares neural substrates with PD in basal ganglia structures
      and the dopamine system. Interestingly, the endogenous cannabinoid system
      modulates dopamine function and subsequently value-based decision making. This
      review will provide an overview of the interdisciplinary research that has
      influenced our understanding of value-based decision making and the role of
      dopamine, particularly in the context of reinforcement learning theories, as well
      as recent animal and human studies that demonstrate the modulatory role of
      activation of cannabinoid receptors by exogenous agonists or their naturally
      occurring ligands. The implications of this research for the symptomatology of
      and potential treatments for PD are also discussed.

PMID- 23162789
TI  - Pregnancy, maternal tobacco smoking, and early age leukemia in Brazil.
AB  - BACKGROUND: Cigarette smoking has been associated with acute myeloid leukemia
      (AML) but hypothesis on the association between maternal smoking during pregnancy
      and childhood leukemia remains unclear. OBJECTIVES: To investigate the
      association between maternal exposure to tobacco smoking during pregnancy and
      early age (<2 year) leukemia (EAL). METHODS: A hospital-based multicenter case
      control study aiming to explore EAL risk factors was carried out in Brazil during
      1999-2007. Data were collected by direct interview with the biological mothers
      using a standardized questionnaire. The present study included 675 children (193
      acute lymphoid leukemia - ALL, 59 AML and 423 controls), being the latter age
      frequency matched and paired by area of residence with the cases. Unconditional
      logistic regression was performed, and odds ratios (OR) on the association
      between tobacco smoking (3 months before pregnancy, during pregnancy, and 3
      months after delivery) and EAL were ascertained after adjustment for selected
      variables (maternal age at birth and education, birth weight, infant skin color,
      and oral contraceptives use during pregnancy). RESULTS: Smoking was reported by
      17.5% of case mothers and 20.6% of controls. Among women who reported to have
      smoked 20 or more cigarettes during the index pregnancy, an adjusted OR = 5.28
      (95% CI 1.40-19.95) for ALL was observed. Heavy smoking during breastfeeding
      yielded an adjusted risk estimate for ALL, OR = 7.78 (95% CI 1.33-45.5). No dose
      response effect was observed according to smoking exposure during pregnancy and
      EAL. An association between secondhand smoking during pregnancy or breastfeeding
      was not observed. CONCLUSION: An association between maternal smoking and EAL in
      the offspring was restricted to women who have reported an intense exposure to
      tobacco smoke during pregnancy and breastfeeding.

PMID- 23162791
TI  - Preclinical evaluation of racotumomab, an anti-idiotype monoclonal antibody to N
      glycolyl-containing gangliosides, with or without chemotherapy in a mouse model
      of non-small cell lung cancer.
AB  - N-glycolylneuraminic acid (NeuGc) is a sialic acid molecule usually found in
      mammalian cells as terminal constituents of different membrane glycoconjugates
      such as gangliosides. The NeuGcGM3 ganglioside has been described as a tumor
      antigen for non-small cell lung cancer (NSCLC) in humans. Racotumomab is an anti
      NeuGc-containing gangliosides anti-idiotype monoclonal antibody (mAb) (formerly
      known as 1E10) that has received attention as a potential active immunotherapy
      for advanced lung cancer in clinical trials. In this work, we have examined the
      antitumor activity of racotumomab in combination or not with chemotherapy, using
      the 3LL Lewis lung carcinoma as a preclinical model of NSCLC in C57BL/6 mice.
      Vaccination with biweekly doses of racotumomab at 50-200 MUg/dose formulated in
      aluminum hydroxide (racotumomab-alum vaccine) demonstrated a significant
      antitumor effect against the progression of lung tumor nodules. Racotumomab-alum
      vaccination exerted a comparable effect on lung disease to that of pemetrexed
      based chemotherapy (100 mg/kg weekly). Interestingly, chemo-immunotherapy was
      highly effective against lung nodules and well-tolerated, although no significant
      synergistic effect was observed as compared to each treatment alone in the
      present model. We also obtained evidence on the role of the exogenous
      incorporation of NeuGc in the metastatic potential of 3LL cells. Our preclinical
      data provide support for the combination of chemotherapy with the anti-idiotype
      mAb racotumomab, and also reinforce the biological significance of NeuGc in lung
      cancer.

PMID- 23162790
TI  - Idiotypes as immunogens: facing the challenge of inducing strong therapeutic
      immune responses against the variable region of immunoglobulins.
AB  - Idiotype (Id)-based immunotherapy has been exploited as cancer treatment option.
      Conceived as therapy for malignancies bearing idiotypic antigens, it has been
      also extended to solid tumors because of the capacity of anti-idiotypic
      antibodies to mimic Id-unrelated antigens. In both these two settings, efforts
      are being made to overcome the poor immune responsiveness often experienced when
      using self immunoglobulins as immunogens. Despite bearing a unique gene
      combination, and thus particular epitopes, it is normally difficult to stimulate
      the immune response against antibody variable regions. Different strategies are
      currently used to strengthen Id immunogenicity, such as concomitant use of immune
      stimulating molecules, design of Id-containing immunogenic recombinant proteins,
      specific targeting of relevant immune cells, and genetic immunization. This
      review focuses on the role of anti-Id vaccination in cancer management and on the
      current developments used to foster anti-idiotypic B and T cell responses.

PMID- 23162792
TI  - Modulating the vascular behavior of metastatic breast cancer cells by curcumin
      treatment.
AB  - The spreading of tumor cells to secondary sites (tumor metastasis) is a complex
      process that involves multiple, sequential steps. Vascular adhesion and
      extravasation of circulating tumor cells (CTCs) is one, critical step. Curcumin,
      a natural compound extracted from Curcuma longa, is known to have anti-tumoral,
      anti-proliferative, anti-inflammatory properties and affect the expression of
      cell adhesion molecules, mostly by targeting the NF-kappaB transcription factor.
      Here, upon treatment with curcumin, the vascular behavior of three different
      estrogen receptor negative (ER(-)) breast adenocarcinoma cell lines (SK-BR-3, MDA
      MB-231, MDA-MB-468) is analyzed using a microfluidic system. First, the dose
      response to curcumin is characterized at 24, 48, and 72 h using a XTT assay. For
      all three cell lines, an IC(50) larger than 20 uM is observed at 72 h; whereas no
      significant reduction in cell viability is detected for curcumin concentrations
      up to 10 uM. Upon 24 h treatment at 10 uM of curcumin, SK-BR3 and MDA-MB-231
      cells show a decrease in adhesion propensity of 40% (p = 0.02) and 47% (p =
      0.001), respectively. No significant change is documented for the less metastatic
      MDA-MB-468 cells. All three treated cell lines show a 20% increase in rolling
      velocity from 48.3 to 58.7 um/s in SK-BR-3, from 64.1 to 73.77 um/s in MDA-MB
      231, and from 57.5 to 74.4 um/s in MDA-MB-468. Collectively, these results
      suggest that mild curcumin treatments could limit the metastatic potential of
      these adenocarcinoma cell lines, possibly by altering the expression of adhesion
      molecules, and the organization and stiffness of the cell cytoskeleton. Future
      studies will elucidate the biophysical mechanisms regulating this curcumin
      induced behavior and further explore the clinical relevance of these findings.

PMID- 23162794
TI  - Radiation-induced changes in microcirculation and interstitial fluid pressure
      affecting the delivery of macromolecules and nanotherapeutics to tumors.
AB  - The immature, chaotic microvasculature of most solid tumors can present a
      significant impediment to blood-borne delivery, uneven distribution, and
      compromised penetration of macromolecular anticancer drugs and diagnostic agents
      from tumor microvessels across the interstitial space to cancer cells. To reach
      viable tumor cells in relevant concentrations, macromolecular agents are
      confronted with several barriers to vascular, transvascular, and interstitial
      transport. Amongst those (1) heterogeneous and poor blood supply, (2) distinctly
      reduced or even abolished hydrostatic and oncotic pressure gradients across the
      microvessel wall abrogating the convective transport from the vessel lumen into
      the interstitial space (impairment of transvascular transport), and (3)
      impediment of convective transport within the interstitial compartment due to
      elevated interstitial fluid pressure (IFP) (resulting from hyperpermeable blood
      vessels coupled with non-functional lymphatics) and a dense structure of the
      interstitial matrix are the major mechanisms hindering drug delivery. Upon
      irradiation, changes in these barrier functions are inconclusive so far.
      Alterations in vascular transport properties following fractionated radiation up
      to 40 Gy are quite inconsistent in terms of direction, extent, and time course.
      Total doses above 45 Gy can damage tumor microvessels, additionally impeding
      vascular delivery. Vascular permeability for macromolecules might be enhanced up
      to a total dose of 45 Gy. However, this effect is counteracted/abolished by the
      elevated IFP in solid tumors. When assessing IFP during fractionated radiotherapy
      in patient tumors, inconsistent alterations have been observed, both in direction
      and extent. From these data it is concluded that modulations in vascular,
      transvascular, and interstitial transport by irradiation of solid tumors are
      rather unclear so far. Translation of experimental data into the clinical setting
      thus needs to be undertaken with especial care.

PMID- 23162793
TI  - Interactions between epigenetics and metabolism in cancers.
AB  - Cancer progression is accompanied by widespread transcriptional changes and
      metabolic alterations. While it is widely accepted that the origin of cancer can
      be traced to the mutations that accumulate over time, relatively recent evidence
      favors a similarly fundamental role for alterations in the epigenome during
      tumorigenesis. Changes in epigenetics that arise from post-translational
      modifications of histones and DNA are exploited by cancer cells to upregulate
      and/or downregulate the expression levels of oncogenes and tumor suppressors,
      respectively. Although the mechanisms behind these modifications, in particular
      how they lead to gene silencing and activation, are still being understood, most
      of the enzymatic machinery of epigenetics require metabolites as substrates or
      cofactors. As a result, their activities can be influenced by the metabolic state
      of the cell. The purpose of this review is to give an overview of cancer
      epigenetics and metabolism and provide examples of where they converge.

PMID- 23162795
TI  - Malignant melanoma and radiotherapy: past myths, excellent local control in 146
      studied lesions at Georgetown University, and improving future management.
AB  - INTRODUCTION: Once thought to be radioresistant, emerging cellular and clinical
      evidence now suggests melanoma can respond to large radiation doses per fraction.
      MATERIALS AND METHODS: We conducted a retrospective study of all patients treated
      with stereotactic radiosurgery and stereotactic body radiotherapy at Georgetown
      University Hospital from May 2002 through November 2008 and studied the classic
      extrapolated total dose corrected for volume (ETD(vol)) model for predicting
      melanoma tumor response. Region-specific tumor outcomes were categorized by
      RECIST criteria and local control curves were estimated and analyzed when
      stratified by ETD(vol) thresholds by use of the Kaplan-Meier method. RESULTS:
      Follow-up information was available for 78 lesions (49 intracranial, 8 spinal,
      and 21 body) with mean follow-up period of 9.2 (range, 2-36) months. 1-year local
      control rates for intracranial, spinal, and body tumors were 84, 100, and 72%,
      respectively. Treatments in general were well-tolerated. Increased ETD(vol) (p <
      0.001) among intracranial sites resulted from larger (p < 0.001) doses per
      fraction combined with smaller (p < 0.001) tumor diameters. Intracranial 6-, 12-,
      and 24-month local control rates when treated above ETD(vol) threshold of 230 Gy
      were all 90 vs. 89, 80, and 53% below this threshold. Body 6- and 12-month local
      control rates when treated above ETD(vol) threshold of 100 Gy were 100 and 80%
      vs. 74 and 59% below this threshold. DISCUSSION: By tailoring to melanoma's
      unique radiobiology with large radiation doses per fraction, favorable local
      control was safely achieved. The ETD(vol) model combines the important factor of
      dose per fraction in melanoma treatment with a volume correction factor to
      predict tumor response. Although limited sample size may have prevented reaching
      statistical significance for local control improvements using ETD(vol)
      thresholds, optimal thresholds may exist to improve future tumor responses and
      further research is required.

PMID- 23162796
TI  - MYCN: from oncoprotein to tumor-associated antigen.
AB  - MYCN is a well-known oncogene over-expressed in different human malignancies
      including neuroblastoma (NB), rhabdomyosarcoma, medulloblastoma, astrocytoma,
      Wilms' tumor, and small cell lung cancer. In the case of NB, MYCN amplification
      is an established biomarker of poor-prognosis. MYCN belongs to a family of
      transcription factors (the most important of which is C-MYC) that show a high
      degree of homology. Down-regulation of MYC protein expression leads to tumor
      regression in animal models, indicating that MYC proteins represent interesting
      therapeutic targets. Pre-requisites for a candidate tumor-associated antigen
      (TAA) to be targeted by immunotherapeutic approaches are the following, (i)
      expression should be tumor-restricted, (ii) the putative TAA should be up
      regulated in cancer cells, and (iii) protein should be processed into immunogenic
      peptides capable of associating to major histocompatibility complex molecules
      with high affinity. Indeed, the MYCN protein is not expressed in human adult
      tissues and up-regulated variably in NB cells, and MYCN peptides capable of
      associating to HLA-A1 or HLA-A2 molecules with high affinity have been
      identified. Thus the MYCN protein qualifies as putative TAA in NB. Additional
      issues that determine the feasibility of targeting a putative TAA with cytotoxic
      T lymphocytes (CTLs) and will be here discussed are the following, (i) the
      inadequacy of tumor cells per se to act as antigen-presenting cells witnessed, in
      the case of NB cells, by the low to absent expression of HLA class I molecules,
      the lack of co-stimulatory molecules and multiple defects in the HLA class I
      related antigen processing machinery, and (ii) the immune evasion mechanisms
      operated by cancer cells to fool the host immune system, such as up-regulation of
      soluble immunosuppressive molecules (e.g., soluble MICA and HLA-G in the case of
      NB) or generation of immunosuppressive cells in the tumor microenvironment. A
      final issue that deserves consideration is the strategy used to generate CTL.

PMID- 23162798
TI  - Comparative genomics and stx phage characterization of LEE-negative Shiga toxin
      producing Escherichia coli.
AB  - Infection by Escherichia coli and Shigella species are among the leading causes
      of death due to diarrheal disease in the world. Shiga toxin-producing E. coli
      (STEC) that do not encode the locus of enterocyte effacement (LEE-negative STEC)
      often possess Shiga toxin gene variants and have been isolated from humans and a
      variety of animal sources. In this study, we compare the genomes of nine LEE
      negative STEC harboring various stx alleles with four complete reference LEE
      positive STEC isolates. Compared to a representative collection of prototype E.
      coli and Shigella isolates representing each of the pathotypes, the whole genome
      phylogeny demonstrated that these isolates are diverse. Whole genome comparative
      analysis of the 13 genomes revealed that in addition to the absence of the LEE
      pathogenicity island, phage-encoded genes including non-LEE encoded effectors,
      were absent from all nine LEE-negative STEC genomes. Several plasmid-encoded
      virulence factors reportedly identified in LEE-negative STEC isolates were
      identified in only a subset of the nine LEE-negative isolates further confirming
      the diversity of this group. In combination with whole genome analysis, we
      characterized the lambdoid phages harboring the various stx alleles and
      determined their genomic insertion sites. Although the integrase gene sequence
      corresponded with genomic location, it was not correlated with stx variant,
      further highlighting the mosaic nature of these phages. The transcription of
      these phages in different genomic backgrounds was examined. Expression of the
      Shiga toxin genes, stx(1) and/or stx(2), as well as the Q genes, were examined
      with quantitative reverse transcriptase polymerase chain reaction assays. A wide
      range of basal and induced toxin induction was observed. Overall, this is a first
      significant foray into the genome space of this unexplored group of emerging and
      divergent pathogens.

PMID- 23162797
TI  - Post-transcriptional regulation of gene expression in Yersinia species.
AB  - Proper regulation of gene expression is required by bacterial pathogens to
      respond to continually changing environmental conditions and the host response
      during the infectious process. While transcriptional regulation is perhaps the
      most well understood form of controlling gene expression, recent studies have
      demonstrated the importance of post-transcriptional mechanisms of gene regulation
      that allow for more refined management of the bacterial response to host
      conditions. Yersinia species of bacteria are known to use various forms of post
      transcriptional regulation for control of many virulence-associated genes. These
      include regulation by cis- and trans-acting small non-coding RNAs, RNA-binding
      proteins, RNases, and thermoswitches. The effects of these and other regulatory
      mechanisms on Yersinia physiology can be profound and have been shown to
      influence type III secretion, motility, biofilm formation, host cell invasion,
      intracellular survival and replication, and more. In this review, we discuss
      these and other post-transcriptional mechanisms and their influence on virulence
      gene regulation, with a particular emphasis on how these processes influence the
      virulence of Yersinia in the host.

PMID- 23162799
TI  - Shiga toxin 2-induced intestinal pathology in infant rabbits is A-subunit
      dependent and responsive to the tyrosine kinase and potential ZAK inhibitor
      imatinib.
AB  - Shiga toxin producing Escherichia coli (STEC) are a major cause of food-borne
      illness worldwide. However, a consensus regarding the role Shiga toxins play in
      the onset of diarrhea and hemorrhagic colitis (HC) is lacking. One of the
      obstacles to understanding the role of Shiga toxins to STEC-mediated intestinal
      pathology is a deficit in small animal models that perfectly mimic human disease.
      Infant rabbits have been previously used to study STEC and/or Shiga toxin
      mediated intestinal inflammation and diarrhea. We demonstrate using infant
      rabbits that Shiga toxin-mediated intestinal damage requires A-subunit activity,
      and like the human colon, that of the infant rabbit expresses the Shiga toxin
      receptor Gb(3). We also demonstrate that Shiga toxin treatment of the infant
      rabbit results in apoptosis and activation of p38 within colonic tissues. Finally
      we demonstrate that the infant rabbit model may be used to test candidate
      therapeutics against Shiga toxin-mediated intestinal damage. While the p38
      inhibitor SB203580 and the ZAK inhibitor DHP-2 were ineffective at preventing
      Shiga toxin-mediated damage to the colon, pretreatment of infant rabbits with the
      drug imatinib resulted in a decrease of Shiga toxin-mediated heterophil
      infiltration of the colon. Therefore, we propose that this model may be useful in
      elucidating mechanisms by which Shiga toxins could contribute to intestinal
      damage in the human.

PMID- 23162801
TI  - Mesenchymal stem cells as a novel vaccine platform.
AB  - Vaccines are the most efficient and cost-effective means of preventing infectious
      disease. However, traditional vaccine approaches have thus far failed to provide
      protection against human immunodeficiency virus (HIV), tuberculosis, malaria, and
      many other diseases. New approaches to vaccine development are needed to address
      some of these intractable problems. In this report, we review the literature
      identifying stimulatory effects of mesenchymal stem cells (MSC) on immune
      responses and explore the potential for MSC as a novel, universal vaccination
      platform. MSC are unique bone marrow-derived multipotent progenitor cells that
      are presently being exploited as gene therapy vectors for a variety of
      conditions, including cancer and autoimmune diseases. Although MSC are
      predominantly known for anti-inflammatory properties during allogeneic MSC
      transplant, there is evidence that MSC can actually promote adaptive immunity
      under certain settings. MSC have also demonstrated some success in anti-cancer
      therapeutic vaccines and anti-microbial prophylactic vaccines, as we report, for
      the first time, the ability of modified MSC to express and secrete a viral
      antigen that stimulates antigen-specific antibody production in vivo. We
      hypothesize that the unique properties of modified MSC may enable MSC to serve as
      an unconventional but innovative, vaccine platform. Such a platform would be
      capable of expressing hundreds of proteins, thereby generating a broad array of
      epitopes with correct post-translational processing, mimicking natural infection.
      By stimulating immunity to a combination of epitopes, it may be possible to
      develop prophylactic and even therapeutic vaccines to tackle major health
      problems including those of non-microbial and microbial origin, including cancer,
      or an infectious disease like HIV, where traditional vaccination approaches have
      failed.

PMID- 23162800
TI  - Escherichia coli O157:H7-Clinical aspects and novel treatment approaches.
AB  - Escherichia coli O157:H7 is a notorious pathogen often contracted by intake of
      contaminated water or food. Infection with this agent is associated with a broad
      spectrum of illness ranging from mild diarrhea and hemorrhagic colitis to the
      potentially fatal hemolytic uremic syndrome (HUS). Treating E. coli O157:H7
      infection with antimicrobial agents is associated with an increased risk of
      severe sequelae such as HUS. The difficulty in treating this bacterium using
      conventional modalities of antimicrobial agent administration has sparked an
      interest in investigating new therapeutic approaches to this bacterium. These
      approaches have included the use of probiotic agents and natural products with
      variable success rates. In addition, novel modalities and regimen of
      antimicrobial agent administration have been assessed in an attempt at decreasing
      their association with aggravating infection outcomes.

PMID- 23162803
TI  - Biological activities and chemical composition of solvent extracts of
      Stoechospermum marginatum (C. Agardh).
AB  - The objective of this study was to evaluate the chemical composition CH3OH-CH2Cl2
      (1:1) extract and biological activities of various extracts derived from the
      aerial parts of the brown marine alga Stoechospermum marginatum (C. Agardh). Gas
      chromatography (GC) and gas chromatography-mass spectroscopy (GC-MS) were used to
      analyze the composition of the essential oil. Total phenolics assay demonstrated
      a high value in hexane extract (HE), with a lower value for chloroform extract
      (CE), and the lowest value for methanol extract (ME). DPPH (2,2-diphenyl-1
      picrylhydrazyl) assay showed that extracts of S. marginatum possess radical
      scavenging activity (RSA). Tests of the antioxidant property of the extracts
      revealed both electron and hydrogen transfer mechanisms. The antibacterial
      activity of the ME, CE, and HE as well as an ethanol extract was estimated
      against seven Gram-positive and Gram-negative bacteria. The ethanol extract
      showed the highest antibacterial activity, and the HE showed the lowest.

PMID- 23162804
TI  - S100A4 promotes invasion and angiogenesis in breast cancer MDA-MB-231 cells by
      upregulating matrix metalloproteinase-13.
AB  - S100A4 is a member of the S100 family of calcium-binding proteins that is
      directly involved in tumor metastasis. In the present study, we examined the
      potential role of S100A4 in metastasis in breast cancer and its relation with
      matrix metalloproteinase-13 (MMP-13). Analysis of 100 breast cancer specimens
      including 50 with and 50 without lymph node metastasis showed a significant
      upregulation of S100A4 and MMP-13 expression in metastatic breast cancer tissues.
      Positive immunoreactivity for S100A4 was associated with MMP-13 expression.
      Overexpression of S100A4 in the MDA-MB-231 breast cancer cell line upregulated
      MMP13 expression leading to increased cell migration and angiogenesis. SiRNA
      mediated silencing of S100A4 downregulated MMP13 expression and suppressed cell
      migration and angiogenesis. Moreover, neutralization of MMP-13 activity with a
      specific antibody blocked cell migration and angiogenesis in MDA-MB-231/S100A4
      cells. In vivo siRNA silencing of S100A4 significantly inhibited lung metastasis
      in transgenic mice. The present results suggest that the S100A4 gene may control
      the invasive potential of human breast cancer cells by modulating MMP-13 levels,
      thus regulating metastasis and angiogenesis in breast tumors. S100A4 could
      therefore be of value as a biomarker of breast cancer progression and a novel
      therapeutic target for human breast cancer treatment.

PMID- 23162802
TI  - Interactions between parasites and microbial communities in the human gut.
AB  - The interactions between intestinal microbiota, immune system, and pathogens
      describe the human gut as a complex ecosystem, where all components play a
      relevant role in modulating each other and in the maintenance of homeostasis. The
      balance among the gut microbiota and the human body appear to be crucial for
      health maintenance. Intestinal parasites, both protozoans and helminths, interact
      with the microbial community modifying the balance between host and commensal
      microbiota. On the other hand, gut microbiota represents a relevant factor that
      may strongly interfere with the pathophysiology of the infections. In addition to
      the function that gut commensal microbiota may have in the processes that
      determine the survival and the outcome of many parasitic infections, including
      the production of nutritive macromolecules, also probiotics can play an important
      role in reducing the pathogenicity of many parasites. On these bases, there is a
      growing interest in explaining the rationale on the possible interactions between
      the microbiota, immune response, inflammatory processes, and intestinal
      parasites.

PMID- 23162805
TI  - Preparation of a polyclonal antibody against hypericin  synthase and localization
      of the enzyme in red-pigmented Hypericum perforatum L. plantlets.
AB  - Hypericum perforatum is well known for its antidepressant and anti-inflammatory
      activities, for which hypericin and its derivatives are indicated to be the most
      active compounds. Hypericin synthase (Hyp-1) is the only protein proven to
      catalyze the synthesis of hypericin. In this study, the full-length cDNA of Hyp-1
      was chemically synthesized according to the Hyp-1 sequence in GenBank (accession
      no. AY148090) and then cloned into the plasmid pET22b. Hyp-1 was expressed in
      Escherichia coli BL21 (DE3) and purified with a Ni-NTA column. The purified
      protein was used to immunize New Zealand white rabbits, from which an antiserum
      was purified by protein G affinity chromatography. The polyclonal antibody
      against Hyp-1 provides a valuable tool for the study of hypericin biosynthesis in
      H. perforatum. Expression of Hyp-1 and the cellular distribution of hypericin
      were analyzed in different organs of red-pigmented H. perforatum plantlets. The
      black glands were not the only site of hypericin accumulation and the results
      indicated that hypericin might be synthesized in mesophyll cells or in tissues of
      the root and/or stem and then transported to the glands. This work provides a
      foundation for further investigation of the regulatory mechanism of hypericin
      synthesis during the development of H. perforatum.

PMID- 23162806
TI  - Salivary proteins in health and disease.
AB  - Besides their structural catalytic and diverse regulatory functions, proteins are
      also precursors of many important biological compounds essential for normal
      functioning of humans. Many of these compounds may be used as markers for
      identification of specific pathological states. A comprehensive knowledge about
      the metabolism of salivary proteins and the mechanisms of action of their
      metabolites allowed the development of effective treatment for many disorders.
      However, it should not be forgotten that in some pathological conditions, these
      compounds not only could be involved in the pathogenesis but also could be used
      as tool in the prediction of many diseases. This paper is a review of the
      published literature on selected salivary proteins in the context of the
      physiological processes of the human body and chosen chronic disorders, such as
      diabetes, diabetic nephropathy, mucositis, oral mycoses and caries.

PMID- 23162807
TI  - Dual, enzymatic and non-enzymatic, function of ecto-5'-nucleotidase (eN, CD73) in
      migration and invasion of A375 melanoma cells.
AB  - Ecto-5'-nucleotidase (eN, CD73) mediates extracellular adenosine production from
      5'-AMP. Non-enzymatic functions of eN have also been reported. The aim of the
      study was to investigate the role of ecto-5'-nucleotidase in aggressive melanoma
      behaviour. Analysis of the involvement of eN in adhesion, migration and invasion
      revealed eN functions unknown to date. We found that following eN blockade by
      concanavalin A, the strength of adhesion to different ECM proteins was not
      altered, but at the same time the invasion ability of the cells was decreased. On
      the other hand, knocking down eN in melanoma cells did not influence cell
      invasion but abolished their migration on tenascin C (TnC). Ecto-5'-nucleotidase
      seems to fulfil a more distinct role as a receptor than as an enzyme in the cell
      interaction and mobility on TnC. Ecto-5'-nucleotidase activates also focal
      adhesion kinase and enhances the formation of complexes upon cell adhesion to
      TnC. All these observations prove that an eN-TnC complex is involved in cell
      migration and invasion and thus in the regulation of melanoma progression.

PMID- 23162809
TI  - Dual-channel cathodic electrochemiluminescence of luminol induced by injection of
      hot electrons on a niobate semiconductor modified electrode.
AB  - In this paper, a new niobate semiconductor photocatalyst
      Sr(0.4)H(1.2)Nb(2)O(6).H(2)O (HSN) nanoparticle was applied to investigate the
      cathodic electrochemiluminescent (ECL) behavior of luminol for the first time.
      The results presented here demonstrated that there were two ECL peaks of luminol
      at the cathodic potential attributed to immobilization of HSN on the electrode
      surface. It is implied that HSN can be electrically excited and injected
      electrons into aqueous electrolytes from this electrode under a quite low
      potential that only excites luminol. A mechanism for this luminol-ECL system on
      HSN/GCE has been proposed. Additionally, this HSN/GCE has lots of advantages,
      such as high stability, good anti-interference ability, simple instrumentation,
      rapid procedure and ultrasensitive ECL response. It is envisioned that this
      HSN/GCE has further applications in biosensors.

PMID- 23162808
TI  - A simple SPR-based method for the quantification of the effect of potential virus
      inhibitors.
AB  - Here, we describe a highly sensitive method that allows for the correct
      quantification of inhibition effect with a higher degree of accuracy directly at
      the molecular level. The protocol involves two stages, namely serological virus
      titration in comparison with the same procedure for virus-effector mixture. Owing
      to the robustness of the analysis this assay can be performed on crude cellular
      and plant extracts, and therefore it may be suitable for the routine analysis of
      clinical samples, or in the field. The efficiency of the approach to the
      quantification of the inhibition effect of polysaccharide glucuronoxylomannan
      (GXM) on the infection efficiency of the tobacco mosaic virus (TMV) was
      investigated using advanced serological approaches based on label-free surface
      plasmon resonance technique. It was shown that GXM drastically decreases the
      efficiency of TMV infection by blocking up to 70% of the virus shell. The
      obtained results are in conformity with the method of indicator plant infection.

PMID- 23162810
TI  - Gravitational field-flow fractionation integrated with chemiluminescence
      detection for a self-standing point-of-care compact device in bioanalysis.
AB  - A "Point-Of-Care-Testing" (POCT) system relies on portable and simply operated
      self-standing analytical devices. To fulfill diagnostic requirements, the POCT
      system should provide highly sensitive simultaneous detection of several
      biomarkers of the pathology of interest (multiplexing) in a short assay time. One
      of the main unsolved issues in POCT device development is the integration of pre
      analytical sample preparation procedures in the miniaturized device. In this
      work, an integrated POCT system based on gravitational field-flow fractionation
      (GrFFF) and chemiluminescence (CL) detection is presented for the on-line sample
      pre-analytical treatment and/or clean-up and analysis of biological fluids. As a
      proof of principle for the new GrFFF-CL POCT system, the automatic on-line
      analysis of plasma alkaline phosphatase activity, a biomarker of obstructive
      liver diseases and bone disorders, starting from whole blood samples was
      developed. The GrFFF-CL POCT system was able to give quantitative results on
      blood samples from control and patients with low sample volume (0.5 MUL) and
      reagent consumption, short analysis time (10 minutes), high reproducibility and
      with a linear range of 50-1400 IU L(-1). The system can be easily applied to on
      line prepare plasma from whole blood for other clinical biomarkers and for other
      assay formats, based on immunoassay or DNA hybridization.

PMID- 23162811
TI  - Ni foam: a novel three-dimensional porous sensing platform for sensitive and
      selective nonenzymatic glucose detection.
AB  - The present communication reports on the first use of commercially available
      three-dimensional porous Ni foam (NF) as a novel electrochemical sensing platform
      for nonenzymatic glucose detection. NF not only acts as a working electrode, but
      also functions as an effective electrocatalyst for electrooxidation of glucose.
      The sensor exhibits high selectivity toward glucose. The linear range and limit
      of detection were 0.05-7.35 mM (R = 0.995) and 2.2 MUM with a signal-to-noise
      ratio of 3, respectively. The application of this glucose sensor in human blood
      serum has also been demonstrated successfully.

PMID- 23162812
TI  - Label-free fluorescent DNA sensor for the detection of silver ions based on
      molecular light switch Ru complex and unmodified quantum dots.
AB  - Using molecular light switch Ru complex Ru(bpy)(2)(dppz)(2+) and CdTe quantum
      dots (QDs), we have designed a label-free DNA fluorescent sensor for the
      detection of Ag(+) in aqueous solution.

PMID- 23162813
TI  - The role of organic and inorganic indoor pollutants in museum environments in the
      degradation of dammar varnish.
AB  - This paper investigates the effects of inorganic (NO(2) and O(3)) and volatile
      organic acid (acetic acid) pollutants on the degradation of dammar varnish in
      museum environments. Model paint varnish samples based on dammar resin were
      investigated by Gas Chromatography Mass Spectrometry (GC-MS), Dynamic Mechanical
      Analysis (DMA) and Atomic Force Microscopy (AFM). Dammar is a natural
      triterpenoid resin, commonly used as a paint varnish. Samples were subjected to
      accelerated ageing by different levels of pollutants (NO(2) and O(3) and acetic
      acid) over a range of relative humidities (RH) and then analysed. The results
      revealed that as the dose of the pollutant was increased, so did the degree of
      oxidation and cross-linking of the resin. Most interestingly, it was shown for
      the first time that exposure to acetic acid vapour resulted in the production of
      an oxidised and cross-linked resin, comparable to the resin obtained under
      exposure to NO(2) and O(3). These conclusions were supported by the analyses of
      model varnishes exposed for about two years in selected museum environments,
      where the levels of pollutants had been previously measured. Exposures were
      performed both within and outside the selected microclimate frames for paintings.
      Results showed that varnishes placed within the microclimate frames were not
      always better preserved than those exposed outside the frames. For some sites,
      the results highlighted the protective effects of the frames from outdoor
      generated pollutants, such as NO(2) and O(3). For other sites, the results showed
      that the microclimate frames acted as traps for the volatile organic acids
      emitted by the wooden components of the mc-frames, which damaged the varnish.

PMID- 23162814
TI  - Potentiometric chemical sensors from lignin-poly(propylene oxide) copolymers
      doped by carbon nanotubes.
AB  - Hardwood and softwood lignins obtained from industrial sulphite and kraft and
      laboratory oxygen-organosolv pulping processes were employed in co-polymerization
      with tolylene 2,4-diisocyanate terminated poly(propylene glycol). The obtained
      lignin-based polyurethanes were doped with 0.72 w/w% of multiwall carbon
      nanotubes (MWCNTs) with the aim of increasing their electrical conductivity to
      the levels suitable for sensor applications. Effects of the polymer doping with
      MWCNTs were assessed using electrical impedance (EIS) and UV-Resonance Raman (UV
      RR) spectroscopy. Potentiometric sensors were prepared by drop casting of liquid
      polymer on the surface of carbon glass or platinum electrodes. Lignin-based
      sensors displayed a very low or no sensitivity to all alkali, alkali-earth and
      transition metal cations ions except Cr(VI) at pH 2. Response to Cr(VI) values of
      39, 50 and 53 mV pX(-1) for the sensors based on kraft, organosolv and
      lignosulphonate lignins, respectively, were observed. Redox sensitivity values
      close to the theoretical values of 20 and 21 mV pX(-1) for organosolv and
      lignosulphonate based sensors respectively were detected in the Cr(III)/Cr(VI)
      solutions while a very low response was observed in the solutions containing
      Fe(CN)(6)(3-/4-). Conducting composite lignin-based polyurethanes doped with
      MWCNTs were suggested as being promising materials for Cr(VI)-sensitive
      potentiometric sensors.

PMID- 23162816
TI  - Comment.

PMID- 23162817
TI  - Comment.

PMID- 23162818
TI  - Comment.

PMID- 23162819
TI  - Comment.

PMID- 23162820
TI  - Comment.

PMID- 23162821
TI  - Comment.

PMID- 23162822
TI  - India's unregulated surrogacy industry.

PMID- 23162824
TI  - Comment.

PMID- 23162823
TI  - Profiteering threatens the altruism of tissue donation.

PMID- 23162825
TI  - Comment.

PMID- 23162826
TI  - Emancipation, sickness, and death in the American Civil War.

PMID- 23162827
TI  - Comment.

PMID- 23162828
TI  - Comment.

PMID- 23162829
TI  - Comment.

PMID- 23162830
TI  - [Comment on Caygill et al].

PMID- 23162832
TI  - Comment.

PMID- 23162831
TI  - Comment.

PMID- 23162833
TI  - [Comment on Pioche et al].

PMID- 23162834
TI  - Comment.

PMID- 23162835
TI  - Comment.

PMID- 23162837
TI  - Comment.

PMID- 23162836
TI  - Comment.

PMID- 23162838
TI  - Comment.

PMID- 23162839
TI  - Comment.

PMID- 23162840
TI  - Comment.

PMID- 23162841
TI  - Comment.

PMID- 23162842
TI  - Comment.

PMID- 23162843
TI  - Comment.

PMID- 23162844
TI  - Comment.

PMID- 23162845
TI  - Comment.

PMID- 23162846
TI  - Comment.

PMID- 23162847
TI  - Comment.

PMID- 23162848
TI  - Comment.

PMID- 23162849
TI  - The self-destructing private sector is no less a blot on our health system than
      the crumbling public health system.

PMID- 23162850
TI  - Some South African universities provide good specialist otorhinolaryngology
      training.

PMID- 23162851
TI  - Thieves of the state- a response.

PMID- 23162852
TI  - Private healthcare 'lost line in the sand' - Zokufa.

PMID- 23162853
TI  - Most SA sunblock products 'can't take the heat', tests show.

PMID- 23162854
TI  - ANC 'lost the plot'on the healthcare policy - union leader.

PMID- 23162855
TI  - Mandatory cover? 'Yes, but not now' - Zokufa.

PMID- 23162856
TI  - [Education Program for Patients with Incontinence -- OALI report].

PMID- 23162857
TI  - [Can sublingual and subcutaneous immunotherapy be combined?].

PMID- 23162858
TI  - Local infiltration analgesia reduced postoperative morphine consumption and
      provided better pain relief than intrathecal morphine after total knee
      arthroplasty.

PMID- 23162859
TI  - Intraoperative periarticular infiltration of levobupivacaine reduced morphine
      consumption in the first twelve hours after total hip arthroplasty.

PMID- 23162861
TI  - Association between nucleoside analogues and risk of hepatitis B virus-related
      hepatocellular carcinoma recurrence following liver resection.
AB  - CONTEXT: Tumor recurrence is a major issue for patients with hepatocellular
      carcinoma (HCC) following curative liver resection. OBJECTIVE: To investigate the
      association between nucleoside analogue use and risk of tumor recurrence in
      patients with hepatitis B virus (HBV)--related HCC after curative surgery.
      DESIGN, SETTING, AND PARTICIPANTS: A nationwide cohort study between October 2003
      and September 2010. Data from the Taiwan National Health Insurance Research
      Database. Among 100 938 newly diagnosed HCC patients, we identified 4569 HBV
      related HCC patients who received curative liver resection for HCC between
      October 2003 and September 2010. MAIN OUTCOME MEASURES: The risk of first tumor
      recurrence was compared between patients not taking nucleoside analogues
      (untreated cohort, n = 4051) and patients taking nucleoside analogues (treated
      cohort, n = 518). Cumulative incidences and hazard ratios (HRs) were calculated
      after adjusting for competing mortality. RESULTS: The treated cohort had a higher
      prevalence of liver cirrhosis when compared with the untreated cohort (48.6% vs
      38.7%; P < .001), but lower risk of HCC recurrence (n = 106 [20.5%] vs n = 1765
      [43.6%]; P < .001), and lower overall death (n = 55 [10.6%] vs n = 1145 [28.3%];
      P < .001). After adjusting for competing mortality, the treated cohort had a
      significantly lower 6-year HCC recurrence rate (45.6%; 95% CI, 36.5%-54.6% vs
      untreated, 54.6%; 95% CI, 52.5%-56.6%; P < .001). Six-year overall mortalities
      for treated cohorts were 29.0% (95% CI, 20.0%-38.0%) and for untreated 42.4% (95%
      CI, 40.0%-44.7%; P < .001). On modified Cox regression analysis, nucleoside
      analogue use (HR, 0.67; 95% CI, 0.55-0.81; P < .001), statin use (HR, 0.68; 95%
      CI, 0.53-0.87; P = .002), and nonsteroidal anti-inflammatory drugs or aspirin use
      (HR, 0.80; 95% CI, 0.73-0.88; P < .001) were independently associated with a
      reduced risk of HCC recurrence. Multivariable stratified analyses verified the
      association in all subgroups of patients, including those who were noncirrhotic
      (HR, 0.56; 95% CI, 0.42-0.76) and diabetic (HR, 0.52; 95% CI, 0.31-0.89).
      CONCLUSION: Nucleoside analogue use was associated with a lower risk of HCC
      recurrence among patients with HBV-related HCC after liver resection.

PMID- 23162862
TI  - Immigration: Waiting for green.

PMID- 23162860
TI  - Multivitamins in the prevention of cancer in men: the Physicians' Health Study II
      randomized controlled trial.
AB  - CONTEXT: Multivitamin preparations are the most common dietary supplement, taken
      by at least one-third of all US adults. Observational studies have not provided
      evidence regarding associations of multivitamin use with total and site-specific
      cancer incidence or mortality. OBJECTIVE: To determine whether long-term
      multivitamin supplementation decreases the risk of total and site-specific cancer
      events among men. DESIGN, SETTING, AND PARTICIPANTS: A large-scale, randomized,
      double-blind, placebo controlled trial (Physicians" Health Study II) of 14 641
      male US physicians initially aged 50 years or older (mean [SD] age, 64.3 [9.2]
      years), including 1312 men with a history of cancer at randomization, enrolled in
      a common multivitamin study that began in 1997 with treatment and follow-up
      through June 1, 2011. INTERVENTION: Daily multivitamin or placebo. MAIN OUTCOME
      MEASURES: Total cancer (excluding nonmelanoma skin cancer), with prostate,
      colorectal, and other site-specific cancers among the secondary end points.
      RESULTS: During a median (interquartile range) follow-up of 11.2 (10.7-13.3)
      years, there were 2669 men with confirmed cancer, including 1373 cases of
      prostate cancer and 210 cases of colorectal cancer. Compared with placebo, men
      taking a daily multivitamin had a statistically significant reduction in the
      incidence of total cancer (multivitamin and placebo groups, 17.0 and 18.3 events,
      respectively, per 1000 person-years; hazard ratio [HR], 0.92; 95% CI, 0.86-0.998;
      P=.04). There was no significant effect of a daily multivitamin on prostate
      cancer (multivitamin and placebo groups, 9.1 and 9.2 events, respectively, per
      1000 person-years; HR, 0.98; 95% CI, 0.88-1.09; P=.76), colorectal cancer
      (multivitamin and placebo groups, 1.2 and 1.4 events, respectively, per 1000
      person-years; HR, 0.89; 95% CI, 0.68-1.17; P=.39), or other site-specific
      cancers. There was no significant difference in the risk of cancer mortality
      (multivitamin and placebo groups, 4.9 and 5.6 events, respectively, per 1000
      person-years; HR, 0.88; 95% CI, 0.77-1.01; P=.07). Daily multivitamin use was
      associated with a reduction in total cancer among 1312 men with a baseline
      history of cancer (HR, 0.73; 95% CI, 0.56-0.96; P=.02), but this did not differ
      significantly from that among 13 329 men initially without cancer (HR, 0.94; 95%
      CI, 0.87-1.02; P=.15; P for interaction=.07). Conclusion In this large prevention
      trial of male physicians, daily multivitamin supplementation modestly but
      significantly reduced the risk of total cancer. TRIAL REGISTRATION:
      clinicaltrials.gov Identifier: NCT00270647.

PMID- 23162863
TI  - Perinatal nanomedicine:  dendrimer-based therapy for  neuroinflammatory
      disorders.

PMID- 23162864
TI  - The importance of size: nanomedicine for delivery of  anticancer drugs in solid
      tumors.

PMID- 23162865
TI  - DNA origami: self-assembled nucleic acid nanoparticles  for siRNA delivery.

PMID- 23162866
TI  - Trimodal imaging of brain tumors using  multifunctional nanoparticles.

PMID- 23162868
TI  - A shaky restart.

PMID- 23162867
TI  - America's carbon compromise.

PMID- 23162869
TI  - Save scientific sites.

PMID- 23162870
TI  - American Cancer Society reports progress in reducing cancer deaths: however, some
      groups still lag behind this trend.

PMID- 23162871
TI  - Cancer prevention and early detection efforts continue to make strides.

PMID- 23162873
TI  - A special vision to see beyond tomorrow.

PMID- 23162872
TI  - [Palmar hyperhidrosis in childhood: thoracoscopic sympathectomy].
AB  - BACKGROUND: Excessive hand sweating, known as palmar hyperhidrosis, is a
      disabling disorder that starts during the childhood, and can have a strong
      negative impact on the quality of life of affected children, as they feel
      rejected by others due to their permanently damp hands, suffering during school
      activities, contact sports and daily games. MATERIAL AND METHODS: Thoracoscopic
      sympathicolysis is easy to perform and has proven to be safe, with a short
      operating time. A review was performed on 48 children who underwent surgical
      treatment of palmar hyperhidrosis and answered a follow-up questionnaire to
      evaluate their level of satisfaction. RESULTS: Considering the final surgical
      results, the 48 patients were completely satisfied with the outcome of the
      operation. Significant complications or adverse effects were not detected.
      CONCLUSIONS: The primary palmar hyperhidrosis is a pathology that entails an
      important reduction in the quality of life of those who suffer it. With the
      results of this technique in hand, we recommend the endoscopic thoracic
      sympathicolysis procedure for the treatment of this pathology in paediatrics. The
      level of patient satisfaction was high.

PMID- 23162874
TI  - The epi- words of medicine.

PMID- 23162875
TI  - The multiple ligament injured (dislocated) knee.

PMID- 23162876
TI  - Inpatient vs. observation: get it right the first time.
AB  - It's often a balancing act to determine if patients should be admitted to the
      hospital or receive observation services as an outpatient, but it's critical to
      get it right the first time so the hospital will get appropriate reimbursement
      and avoid having money taken away following audits. Reimbursement is much lower
      for observation services, but if a patient is admitted inappropriately, Medicare
      or other payers can take back the reimbursement. Patients receiving observation
      services as outpatients are subject to Medicare Part B co-pays. If the patient is
      later admitted, the time in observation doesn't count toward the three-midnight
      inpatient stay requirement for Medicare to pay for a skilled nursing home
      admission. One-, two-, and three-day stays are often targets of auditors. Case
      managers must work closely with physicians to help them determine the appropriate
      level of care. In certain circumstances, Condition Code 44 can be used to change
      a patient's level of care from inpatient to observation.

PMID- 23162877
TI  - Educate physicians on level of care, documentation.

PMID- 23162878
TI  - Inappropriate admissions mean more paperwork.

PMID- 23162879
TI  - Hospital initiative reduces heart failure readmissions.
AB  - UConn Health Center/John Dempsey Hospital, Farmington, CT, reduced 30-day heart
      failure readmissions from 25.1% in August 2010 by analyzing readmissions and
      looking for ways to improve the discharge process. When patients can't schedule a
      timely appointment with providers who are not part of the healthcare system, the
      case manager schedules one appointment with the hospital's heart failure clinic.
      The team created an easy-to-understand medication booklet, got patient input
      about which heart failure educational booklet to use, and created a heart failure
      video for patients, families, and staff. Hospital representatives meet monthly
      with representatives from post-acute providers to collaborate on improving
      transitions.

PMID- 23162880
TI  - 'Strategic triad' initiatives help health system cut LOS.

PMID- 23162881
TI  - Hospital reduces med errors to 0.1 per 1,000.

PMID- 23162882
TI  - Got culture change? CUSP tools can transform safety.

PMID- 23162883
TI  - It's in insurers' interest to help cut readmissions.

PMID- 23162884
TI  - Vagus nerve stimulation (CardioFit System) for treating congestive heart failure.
      A summary of ECRI institute's health technology forecast report.

PMID- 23162885
TI  - Young physicians not keen on rural areas.

PMID- 23162886
TI  - How insurers & hospitals intend to contain costs.

PMID- 23162887
TI  - Closer look: autofluorescence for oral cancer detection.

PMID- 23162888
TI  - MGMA comments on proposed 2013 Medicare physician fee schedule.

PMID- 23162889
TI  - CMS releases critical HIT regulations that impact practices.

PMID- 23162890
TI  - [Pharmacokinetics and administration of drugs in patients with hepatic failure].

PMID- 23162891
TI  - [The molecular physiological and genetic mechanisms underlying the superb
      efficacy of quinolones].
AB  - The fluoroquinolones are the most widely used broad-spectrum antibiotics,
      accounting for 18% of global antibacterial market share. They can kill bacteria
      rapidly with variety of derivatives available. Different quinolones vary
      significantly in rate and spectrum of killing, oxygen requirement for metabolism
      and reliance upon protein synthesis. Further understanding the sophisticated
      mechanisms of action of this important antibiotic family based on the molecular
      genetic response of bacteria can facilitate the discovery of better quinolone
      derivatives. Factors such as SOS response, bacterial toxin-antitoxin system,
      programmed death, chromosome fragmentation and reactive oxygen have been
      implicated in the action to some extent. "Two steps characteristic" of quinolones
      killing is also emphasized, which might inspire future better quinolones
      modification.

PMID- 23162892
TI  - [Research progress on intracellular metabolites based on metabolomics].
AB  - Being an essential component of systematic biology, metabolomics has received
      attention in recent years. It is a post genomic technology aimed at qualitative
      and quantitative analysis of all low molecular-mass metabolites present in
      complex biological samples, and mainly investigates the change of endogenous
      metabolites of a stimulated or disturbed biological system. Investigations into
      intracellular endogenous metabolites in metabolomics have great advancement in
      recent years. This review outlines the progress of metabolomics in cell culture
      analysis including sample preprocessing methods and metabolite target analysis,
      metabolic profiling analysis, metabolomics analysis and metabolic footprinting
      analysis.

PMID- 23162893
TI  - [Research progress in co-delivery of gene and chemotherapy drugs with cationic
      liposome carrier for cancer therapy].
AB  - Despite recent advances in conventional therapeutic approaches for cancer, the
      efficacy of chemotherapy for cancer is limited due to the drug resistance and
      toxic side effects during treatment. To overcome drug resistance, higher doses of
      the toxic chemotherapy drugs are frequently administered, thus leading to even
      severe adverse side effects, which have limited their clinical application.
      Cationic liposome as a novel non-viral carrier for co-delivery of gene and
      chemotherapy drugs in cancer gene therapy has already attracted more and more
      attention in recent years. Most importantly, this combined strategy can generate
      a significant synergistic effect, which can silence the related gene expression
      and increase the concentration of the intracellular chemotherapy drugs. This
      approach allows the use of a much lower dose of the chemotherapy drugs to achieve
      same therapeutic effect, which may have the potential for overcoming some major
      limitations of the conventional chemotherapy. In conclusion, co-delivery of gene
      and chemotherapy drugs with cationic liposome delivery system will play a vital
      role in the future and especially could be a promising clinical treatment for
      drug-resistant tumors.

PMID- 23162894
TI  - Effect of heparin-derived oligosaccharide on vascular smooth muscle cell
      proliferation through inhibition of PKC-alpha expression.
AB  - In this study, the effect of heparin-derived oligosaccharide (HDO) on bovine
      vascular smooth muscle cell (VSMC) proliferation and signal transduction
      mechanism involved were investigated. The levels of PKC-alpha protein and mRNA
      were determined by cell-based ELISA, RT-PCR, Western blotting and
      immunocytochemical methods. Meanwhile, mRNA levels of c-jun, c-myc and c-fos were
      assayed by RT-PCR method. The results showed that HDO inhibited newborn calf
      serum (NCS)-induced expression of PKC-alpha and proto-oncogenes, which may be one
      of the mechanisms for the inhibition of VSMC proliferation by HDO. Flow cytometry
      analysis indicated that HDO blocked NCS-induced cell cycle progression by
      arresting cells at G0/G1 phase. The results imply that HDO inhibits VSMC
      proliferation by moderating the gene level of PKC-alpha, eventually inhibiting
      proto-oncogene mRNA expression and blocking G1/S transition.

PMID- 23162895
TI  - [Pharmacodynamic study of racemic TJ0711 on renal hypertensive rats after long
      term administration].
AB  - The study is to observe the effect of racemic TJ0711 on blood pressure and heart
      rate as well as protection of cardiovascular system of renal hypertensive rats
      after long-term administration. The renal hypertensive models were established by
      the two-kidney, one-clip (2K1C) method in Wistar rats. Four weeks later, assigned
      the rats whose SBP had increased at least 4 kPa randomly into 5 groups: racemic
      TJ0711 10, 20 and 40 mg x kg(-1) groups, carvedilol control group, model group
      and sham group (n=10), ig administration once daily. The changes of BP (blood
      press) and HR (heart rate) before and after administration were measured by tail
      cuff method weekly. Plasma samples of all animals were taken in 6-8 weeks, and
      plasma MDA as well as renin, angiotensin II (Ang II) and endothelin-1 (ET-1)
      levels were measured. Left ventricle was cut off after 9 weeks, and left
      ventricular weight index (LVWI) and hydroxyproline were measured. The significant
      decrease of the BP of TJ0711 40 mg x kg(-1) group was observed after TJ0711 ig
      administration for 4 weeks, and this effect remained till the end of the study.
      In 8th week, the systolic blood pressure values were: TJ0711 40 mg x kg(-1) group
      18.93 +/- 1.82 kPa (vs 21.30 +/- 2.30 kPa, P < 0.05); 20 mg x kg(-1) group 20.68
      +/- 3.29 kPa (vs 22.19 +/- 2.88 kPa). The plasma MDA level of all treated groups
      was significantly lower than that of model group, so were the plasma renin, Ang
      II and ET-1 levels (P < 0.05). LVWI and hydroxyproline content of myocardial
      tissue decreased to some extent, but was not significant as compared with that of
      model group. The study showed that TJ0711 repeated dosing could reduce BP level
      beginning from drug administration; besides block adrenal alpha and beta
      receptors to play an antihypertensive role. The sustained antihypertensive effect
      also related to reduce plasma vasoconstrictor substances and oxidation product
      MDA. These effects benefited cardiovascular protection.

PMID- 23162896
TI  - [Effects of isorhamnetin on CYP3A4 and herb-drug interaction].
AB  - The study is to report the investigation of the effects of isorhamnetin on CYP3A4
      and herb-drug interaction. A reporter gene assay is used to test pregnane X
      receptor transactivation action, qRT-PCR and a luminescence-based assay were
      applied to determine mRNA induction and enzyme activity of CYP3A4 after
      isorhamnetin treatment. The interaction of irinotecan and isorhamnetin was
      assessed by inhibition assay of cell proliferation. Isorhamnetin at 1, 10 and 25
      micromol x L(-1) transactivated the CYP3A4 reporter construct and upregulated
      CYP3A4 mRNA as well in a dose-dependent manner. However, isorhamnetin had no
      effect on enzyme activity of CYP3A4 and irinotecan HepG2 cytotoxicity. In
      conclusion, activation of PXR by isorhamnetin played a role in the upregulation
      of CYP3A4 mRNA. Moreover, joint action of isorhamnetin with other drugs may not
      be associated with the herb-drug interaction.

PMID- 23162897
TI  - [Shizukaol F: a new structural type inhibitor of HIV-1 reverse transcriptase
      RNase H].
AB  - This study is to investigate the mechanism of action of lindenane
      disesquiterpenoid shizukaol F on HIV-1 replication. Real time quantity PCR, ELISA
      assay and fluorescence methods were used to test HIV-1 reverse transcription
      process, RNA-dependent DNA polymerase activity, and RNase H activity,
      respectively. It showed that shizukaol F inhibited LTR/Gag production of HIV-1
      reverse transcription with an IC50 of 9.11 micromol x L(-1). This result is
      consistent with its inhibitory effect on HIV-1 replication (IC50 of 6.12 micromol
      x L(-1)). Mechanism studies showed that compound shizukaol F inhibited HIV-1 RT
      RNase H with IC50 of 26.4 micromol x L(-1), but had no effect on HIV-1 RT RNA
      dependent DNA polymerase activity. In conclusion, shizukaol F is a new structural
      type HIV-1 RNase H inhibitor. This discovery will provide a clue for new type of
      reverse transcriptase inhibitors development.

PMID- 23162899
TI  - [Classification and distribution analysis of components in Glycyrrhiza using
      licorice compounds database].
AB  - In order to study the chemical components of licorice deeply and systematically,
      a licorice compounds database was established after the comprehensive summary of
      the compounds in Glycyrrhiza. The database was used to classify the licorice
      components anew in order to statistically analyze the distribution of each type
      of compounds and the compounds in the medical Glycyrrhiza plants. The results
      indicated that 422 compounds had been reported in Glycyrrhiza so far, and they
      could be categorized into 5 classes as flavoids, coumarins, triterpenoids,
      stilbenoids, and some others. Up to now, 170 compounds were isolated from G.
      uralensis, 134 compounds from G. glabra, 52 compunds from G. inflata, and 31 from
      G. yunnanensis. It is the first time to add categorization "stilbenoids", and
      "dibenzoylmethanes" classified as chalcones. In the meantime, the database is
      supposed to be convenient for further study.

PMID- 23162898
TI  - Part IV: Design, synthesis and antitumor activity of fluoroquinolone C-3
      heterocycles: bis-oxadiazole methylsulfide derivatives derived from
      ciprofloxacin.
AB  - To explore an efficient strategy for further development of anticancer
      fluoroquinolone candidates derived from ciprofloxacin, a heterocyclic ring as the
      bioisosteric replacement of C3 carboxyl group led to a key intermediate,
      oxadiazole thiol (5), which was further modified to the bis-oxadiazole
      methylsulfides (7a-7h) and the corresponding dimethylpiperazinium iodides (8a
      8h), respectively. Structures were characterized by elemental analysis and
      spectra data, and their anticancer activities in vitro against CHO, HL60 and
      L1210 cancer cells were also evaluated by MTT assay. The preliminary results show
      that piperazinium compounds (8) possess more potent activity than that of
      corresponding free bases (7).

PMID- 23162900
TI  - [Analysis of primary metabolites of ranolazine in dog urine by LC-MS(n)].
AB  - Ranolazine and metabolites in dog urine were identified by LC-MS(n). Dog urine
      samples were collected after ig 30 mg x kg(-1) ranolazine, then the samples were
      enriched and purified through solid-phase extraction cartridge. The purified
      samples were analyzed by LC-MS(n). The possible metabolites were discovered by
      comparing the full scan and SIM chromatograms of the test samples with the
      corresponding blanks. Seventeen phase I metabolites and fourteen phase II
      metabolites were identified in dog urine. Three metabolites were identified by
      comparing with the control article. The metabolites were formed via the following
      metabolic pathways: O-demethylation, O-dearylation, hydroxylation, N
      dealkylation, amide hydrolysis, glucuronidation and sulfation. The LC-MS(n)
      method is suitable for the rapid identification of drug and its metabolites in
      biologic samples.

PMID- 23162901
TI  - [HPLC determination of the related substances in erdosteine].
AB  - An HPLC method was established for the determination of the related substance in
      erdosteine. Waters ODS-SunFire (250 mm x 4.6 mm ID, 5 microm) column was used,
      the mobile phase was composed of methanol-acetonitrile-0.01 mol x L(-1) citric
      acid (20:4:76, the pH value was adjusted by triethylamine to 2.5). The flow rate
      was 1 mL x min(-1). The detection wavelength was 254 nm. The related substances
      in the sample of erdosteine taken were calculated by self control with or without
      the response factor of impurity relative to that of erdosteine. Under the
      chromatographic condition developed, the impurities in erdosteine were isolated
      well. The detection limit was 0.2 microg x mL(-1) (signal/noise = 3) by principal
      component calculated. The method can be adopted to control the related substances
      in erdosteine.

PMID- 23162902
TI  - [The incompatibility mechanism based on the interaction of multiple-components
      for Flos Genkwa and Radix et Rhizoma Glycyrrhizae].
AB  - By investigating the interaction between components from Flos Genkwa (FG) and
      Radix et Rhizoma Glycyrrhizae (RRG) and the dissolution profile of toxic
      components in co-decoction, the characteristics and possible mechanism of
      incompatibility were revealed. Ultra-high performance liquid chromatography
      quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS) and ultra-high
      performance liquid chromatography triple-quadrupole mass spectrometry (UPLC
      TQ/MS) were used to analyze multi-components in different herb extractions
      prepared by different ratios of FG/FG processed by vinegar (FGV) and RRG, which
      reflect the interaction and characteristics of multiple components in
      incompatibility combinations. The results showed that the components dissolution
      was influenced by compatibility ratio with certain regularity. Whether FG
      processed by vinegar or not, with the increase of RRG in co-decoction, the
      dissolution of diterpenes, especially for yuanhuacine, yuanhuadine and
      yuanhuajine, the toxic ingredients of FG, increased significantly. From these
      results, the material basis and one possible mechanism of incompatibility between
      FG and RRG is the increasing dissolution of diterpenes, toxic components of FG in
      co-decoction process, which caused by interaction between multi-components in
      these two herbs.

PMID- 23162903
TI  - [Evaluating method of the characteristic physical properties of the wetting mass
      using texture analyser].
AB  - To build the evaluating method of the characteristic physical properties of the
      wetting mass, this study reported the preparation of wetting mass by adding water
      into microcrystalline cellulose, and using texture analyser texture profile
      analysis to test its physical properties, including hardness, adhesiveness,
      springness, cohesiveness, chewiness, resilience and so on, then finding out the
      better method and parameters. The method was evaluated and used to test wetting
      mass, which was made of microcrystalline cellulose of different types and
      polyvinylpyrrolidone. When running texture profile analysis whose trigger force
      was 1500 g, the relative standard deviation was under 10%, and the trend of every
      characteristic physical property tallied with the theory result by water ratio
      increase. Testing result of the same excipient with the same water ratio had a
      higher precision, while characteristic physical properties of wetting mass who
      was made of the same excipient with different water ratios and different
      excipients had a great difference. Using texture analyser to test physical
      properties of wetting mass could get a result which tallied with the theory by
      water ratio increase, and had a well precision, accuracy and sensitivity, and
      thus it could also evaluate the characteristic physical properties of wetting
      mass relatively well.

PMID- 23162904
TI  - [In vitro and in vivo evaluation of total flavones of Hippophae rhamnoides self
      microemulsifying drug delivery system].
AB  - The goal of the study is to evaluate the self-microemulsifying drug delivery
      system (SMEDDS) which enhances the oral bioavailability of the poorly water
      soluble drug, total flavones of Hippophae rhamnoides (TFH). It is orally
      administered for the protection of human cardiovascular system. Self
      microemulsifying time, particle size, polydispersity index (PDI), morphological
      characterization, in vitro dispersity, stability, in situ intestinal absorption
      and relative bioavailability were investigated in detail. The TFH-SMEDDS rapidly
      formed fine oil-in-water microemulsions with 0.1 mol x L(-1) hydrochloride
      solution, with average size of which was less than 40 nm, PDI was below 0.2, and
      the particles of which were observed round-shaped under transmission electron
      microscope. Almost 90% of TFH (expressed with quercetin) was released from SMEDDS
      within 20 min, which was remarkably higher than that from common capsules. The
      stability test showed the TFH-SMEDDS maintained stable in 6 months under
      accelerated condition. In situ absorption study demonstrated the absorption rate
      constant of TFH-SMEDDS (expressed with quercetin) was significantly higher than
      that of TFH in ethanolic solution (P < 0.05). The absorption of TFH from SMEDDS
      showed a 4.18-fold increase in relative bioavailability (expressed with
      quercetin) compared with that of the suspension. The results suggest that SMEDDS
      is a promising drug delivery system to increase the oral bioavailability of TFH.

PMID- 23162905
TI  - [Achene morphology cluster analysis of Taraxacum F. H. Wigg. from northeast China
      and molecule systematics evidence determined by SRAP].
AB  - The achenes morphological and micro-morphological characteristics of six species
      of genus Taraxacum from northeastern China as well as SRAP cluster analysis were
      observed for their classification evidences. The achenes were observed by
      microscope and EPMA. Cluster analysis was given on the basis of the size, shape,
      cone proportion, color and surface sculpture of achenes. The Taraxacum inter
      species achene shape characteristic difference is obvious, particularly spinulose
      distribution and size, achene color and achene size; with the Taraxacum plant
      achene shape the cluster method T. antungense Kitag. and the T. urbanum Kitag.
      should combine for the identical kind; the achene morphology cluster analysis and
      the SRAP tagged molecule systematics's cluster result retrieves in the table with
      "the Chinese flora". The class group to divide the result is consistent.
      Taraxacum plant achene shape characteristic stable conservative, may carry on the
      inter-species division and the sibship analysis according to the achene shape
      characteristic combination difference; the achene morphology cluster analysis as
      well as the SRAP tagged molecule systematics confirmation support dandelion
      classification result of "the Chinese flora".

PMID- 23162906
TI  - [Genomics and synthetic biology of traditional Chinese medicine].
AB  - Traditional Chinese medicine (TCM) genomics and TCM synthetic biology are two hot
      fields in the TCM modernization. TCM genomics, including transcriptomics,
      structural genomics, genomic markers and functional genomics, aims to elucidate
      the biosynthetic pathways of TCM bioactive compounds and mine the related genes
      encoding enzymes involved in these pathways by analyzing genetic information on
      the original species of TCM, thus promoting the development of TCM synthetic
      biology, genome-assisted molecular identification and molecular breeding, and
      elucidation of the genetic mechanism underlying "Daodi". Genomics and related
      research provide us much deeper understanding of life process and improve our
      ability to create new life or modify the present organisms. Based on TCM
      genomics, TCM synthetic biology sets up a series of procedures to realize the
      production of TCM pharmacological active compounds in microorganism, including
      screening and modification of parts and devices, establishment of standardized
      part and device libraries, and reconstruction and modification of the
      biosynthetic pathway of TCM pharmacological active compounds in microorganism.
      TCM synthetic biology will provide a new resource of TCM pharmacological active
      compounds for the pharmacological study and research & development of new drugs,
      thus enhancing the core competitiveness of our pharmaceutical industry in the
      international markets.

PMID- 23162907
TI  - [Cloning and analysis of squalene synthase (HsSQS1) gene in Huperzia serrata].
AB  - Squalene synthase (SQS) is a key enzyme in plant terpenoid biosynthetic pathway.
      This study focused on cloning and analysis of Huperzia serrata SQS (HsSQS1) gene.
      After searching the transcriptome dataset of H serrata, one unique sequence
      encoding SQS was discovered. The primers were designed according to the
      transcript sequence of HsSQS1 from the H. serrata transcriptome dataset. The open
      reading frame of HsSQS1 was cloned using RT-PCR strategy. The bioinformatic
      analysis of this gene and its corresponding protein were performed. The cDNA
      (named as HsSQS1) contains a 1263 bp open reading frame and encodes a predicted
      protein of 420 amino acids. The GenBank accession number for this gene is
      JQ004938. HsSQS1 contains two transmembrane regions, without signal peptide. The
      conserved domain of squalene synthase was presented in HsSQS1. HsSQS1 was more
      abundant in H. serrata root than in leaf and stem. This study cloned and analyzed
      squalene synthase gene from H. serrata for the first time. The result will
      provide a foundation for exploring the mechanism ofterpenoid biosynthesis in H.
      serrata plants.

PMID- 23162908
TI  - [Full-length cDNA cloning and bioinformatics analysis of PnUGT1 gene in Panax
      notoginseng].
AB  - After searching the transcriptome dataset of Panax notoginseng, one unique
      sequence Pn02086 encoding UDP-glucosyltransferase (UGT), which may be involved in
      triterpene saponin biosynthesis, was discovered. The open reading frame of the
      UGT gene, named as PnUGT1, was cloned by 5'-RACE and RT-PCR method from P.
      notoginseng. The GenBank accession number for this gene is JX018210. The
      bioinformatic analysis of this gene and its corresponding protein was performed.
      The PnUGT1 gene contains a 1488 bp open reading frame and encodes a predicted
      protein of 495 amino acids. The molecular weight is 55.453 kD and the protein is
      unstable. In the secondary structure, the percentage of alpha helix, beta turn,
      random coil were 36.16%, 11.31%, 52.53%, respectively. The PnUGT1 contains 7
      conserved domains predicted by InterProScan, including PSPG-box which is a unique
      consensus sequence of glycosyltransferases involved in plant secondary
      metabolism. The PnUGT1 was most likely to be located in the cytoplasm, without
      signal peptide and transmembrane region. Sequence alignment and phylogenetic
      analysis demonstrated that PnUGT1 had relative close relationship to the
      triterpene UDP-glucosyltransferase of Medicago truncatula (AAW56092), with the
      66% similarity of conserved domain PSPG-box. PnUGT1 was more abundant in P.
      notoginseng leaf than in flower, stem and root. Therefore, PnUGT1 gene may be
      involved in notoginsenoside biosynthesis.

PMID- 23162909
TI  - [Cloning and analysis of mevalonate kinase (PnMVK1) gene in Panax notoginseng].
AB  - Mevalonate kinase (MVK) is a key enzyme in plant terpenoid biosynthetic pathway.
      This study focused on cloning and analysis of Panax notoginseng (Burk.) F. H.
      Chen MVK (PnMVK1) gene. After searching the transcriptome dataset of P.
      notoginseng, one unique sequence encoding MVK was discovered. The primers were
      designed according to the transcript sequence of PnMVK1 from the P. notoginseng
      transcriptome dataset. And then, the open reading frame of PnMVK1 was cloned from
      P. notoginseng by using RT-PCR strategy. The physical and chemical properties,
      secondary structure and three-dimensional structure of the PnMVK1 protein were
      forecasted and analyzed, and its structure and function were predicted. The cDNA
      (named as PnMVK1) contains a 1164 bp open reading frame and encodes a predicted
      protein of 387 amino acids. The GenBank accession number for this gene is
      JQ957844. No transmembrane region and signal peptide were present in PnMVK1. The
      conserved domain of mevalonate kinase was present in PnMVK1. PnMVK1 was more
      abundant in P. notoginseng root than other organisms. This study cloned and
      analyzed PnMVK1 gene from P. notoginseng for the first time. The result will
      provide a foundation for exploring the mechanism of terpenoid biosynthesis in P.
      notoginseng plants.

PMID- 23162910
TI  - [Stability and accuracy of the identification of Notopterygii Rhizoma et Radix
      using the ITS/ITS2 barcodes].
AB  - In this study, Notopterygii Rhizoma et Radix was used to verify the stability and
      accuracy of DNA barcodes in identification of Chinese materia medica for the
      first time. All genomic DNAs from thirty one samples were extracted. The ITS
      (internal transcribed spacer) regions were amplified and sequenced bi
      directionally. Obtained sequences were assembled using the CodonCode Aligner. And
      the sequences of the ITS regions were aligned through Clustal-W and the genetic
      distances were computed using MEGA 5.0 in accordance with the kimura 2-parameter
      (K2P) model. The neighbor-joining (NJ) phylogenetic trees were constructed. The
      ITS2 regions were obtained by using the hidden Markov model (HMM)-based
      annotation methods from the ITS sequences. Results indicated that the lengths of
      ITS regions of Notopterygii Rhizoma et Radix were 603-604 bp, while the lengths
      of ITS2 regions were 228 bp. The haplotypes of ITS/ITS2 regions of Notopterygii
      Rhizoma et Radix were the same as those of the original plant leaves. The intra
      specific genetic distances were smaller than inter-specific ones in ITS/ITS2
      regions of Notopterygium incisum and N. franchetii. The NJ trees showed that N.
      incisum, N. franchetii and its adulterants can be easily differentiated according
      to their monophyly. Therefore, ITS/ITS2 regions as DNA barcodes can stably and
      accurately distinguish Notopterygii Rhizoma et Radix from its adulterants and
      could provide a new technique to ensure clinical safety in utilization of
      traditional Chinese medicines.

PMID- 23162911
TI  - [The mechanical wound transcriptome of three-year-old Aquilaria sinensis].
AB  - Chinese agarwood is formed in the aromatic resinous wood formed in Aquilaria
      sinensis (Lour.) Gilg (botanical family: Thymelaeaceae). Only when suffering
      stress of wound, etc, can A. sinensis produce sesquiterpenes etc. compounds of
      agarwood around wounds. However, little is known about how wound induced the
      biosynthesis pathway of sesquiterpenes. To reveal the molecular mechanism of
      wound-induced agarwood formation, RNA sequencing (RNA-seq) technology was used to
      investigate the profile of gene expression in A. sinensis treated by mechanical
      wounding and elucidate its functional gene. A total of 40,295 ESTs with an
      average read length of 305 bp were generated and 22 095 unigenes were formed by
      initial gene splicing. 61.6% of these unigenes (13 611) were annotated using
      BLAST searches against the SwissProt, KEGG, Nr and Nt databases. Twenty-six
      unigenes (encoding 7 enzymes) were found to be involved in sesquiterpene of
      agarwood biosynthesis by bioinformatic tools of Gene Ontology and KEGG. Novel
      genes that are potentially involved in sesquiterpenes biosynthesis were
      identified in A. sinensis, providing data for further sesquiterpenes biosynthesis
      pathway by molecular methods and the EST data establish a foundation for future
      studies in the molecular mechanisms of wound-induce agarwood formation in A.
      sinensis.

PMID- 23162912
TI  - Rising to the top. Industry groups quiet about Ryan's effect on policies.

PMID- 23162913
TI  - 25 largest ambulatory surgery centers. Ranked by total procedures performed in
      2011.

PMID- 23162915
TI  - Violence and accidents, a challenge for the Unified Health System.

PMID- 23162914
TI  - Chemical compositions of essential oils from Xyloselinum vietnamense and X.
      selinum leonidii.
AB  - The chemical compositions of essential oils obtained by hydrodistillation from
      leaves and stems of Xyloselinum vietnamense and X. leonidii, two new species
      belonging to the family Apiaceae, were analyzed by GC-MS. The major components in
      both species were sabinene, alpha- and beta-pinene, myrcene, beta-phellandrene,
      (Z)-beta-ocimene, and terpinen-4-ol. The monoterpene sabinene was most abundant
      in the leaves of X. vietnamense (75.0%). These compounds might be considered as
      chemotaxonomic markers of Xyloselinum species. In the DPPH radical scavenging
      assay, all four essential oils showed moderate activity, while the water extracts
      exhibited stronger effects. The strong DPPH scavenging activity of the water
      residues of X. vietnamens and X. leonidii might be due to their phenolic
      components. This paper is the first report on the chemical compositions and
      antioxidant activity of X. vietnamens and X. leonidii.

PMID- 23162916
TI  - SCOTUS invalidates West Virginia blanket prohibition against arbitration.

PMID- 23162917
TI  - The scope of practice for physician assistants limits what tasks they may
      perform.

PMID- 23162918
TI  - Affirmative evidence defeats claim of birth injury.

PMID- 23162919
TI  - EMTALA not applicable if patient stable on discharge.

PMID- 23162920
TI  - Psychiatrist may have had a duty to commit patient involuntarily.

PMID- 23162921
TI  - [Expression of serum sICAM-1 in patients with primary hepatocellular carcinoma
      and its relationship with liver fibrosis].
AB  - AIM: To explore the clinical value of serum soluble intercellular adhesion
      molecule-1 (sICAM-1) in patients with primary hepatocellular carcinoma (PHC) and
      its relationship with liver fibrosis. METHODS: The serun sICAM-1, PC III, IV-C,
      LN and HA level of 45 cases of patients with PHC, 30 cases of benign tumor and 35
      cases of healthy people were determined by ELISA, the relationship between sICAM
      1 and liver fibrosis was analyzed. RESULTS: The serum sICAM-1, PC III, IV-C, LN
      and HA levels of the PHC group were significantly higher than that of the benign
      tumor group and normal control group, compared the difference was significant
      (P<0.05); The serum markers was no significant difference between the benign
      tumor group and normal control group (P>0.05); The serum sICAM-1 was positively
      correlated with the PC III, IV-C, LN and HA (gamma= 0.683, 0.575, 0.573 and
      0.539, P<0.05). CONCLUSION: Detection of serum sICAM-1 has important clinical
      significance for assessing the PHC patient's condition, early diagnosing and
      treating liver cancer.

PMID- 23162922
TI  - [Establishment of a high throughput screening model of cannabinoid receptor 2
      agonist].
AB  - AIM: To establish a drug screening model of CB(2) agonist in vitro based on
      signal regulation pathway. METHODS: Plasmid pIRES(2)-EGFP-CB(2), pGL(4),
      29[luc2P/CRE/Hygro] and PRL-TK were co-transfected into CHO cells in 96 wells
      plate, to screen agonists of CB(2) receptor by detecting the expressing levels of
      dual luciferase activity. The concentration and acting time of the agonist were
      optimized and the stability of the model were investigated. RESULTS: The largest
      relative induction activity was obtained after 8h drug administration.
      Establishment of a high throughput screening model for CB(2) receptor agonist.
      The Z' factor is 0.75 demonstrating its perfect stability. CONCLUSION:
      Successfully establish a drug screening model of CB(2) agonist, which provided a
      basis for searching valid material from traditional Chinese medicine.

PMID- 23162923
TI  - An unusual complication of rapid weight loss.

PMID- 23162924
TI  - Beyond pharyngitis....

PMID- 23162925
TI  - The curious case of the disappearing teen.

PMID- 23162926
TI  - Acute neck pain following a large meal and vomiting.

PMID- 23162927
TI  - Evolving neurologic symptoms in a previously healthy adolescent male.

PMID- 23162928
TI  - "Picky" eater with a stomping gait.

PMID- 23162929
TI  - Fever, cough, and syncope in a critically ill adolescent.

PMID- 23162930
TI  - Leg swelling a patient with anorexia nervosa.

PMID- 23162931
TI  - Do television exercise commercials contribute to eating disorders?

PMID- 23162932
TI  - An adolescent evaluated for chronic fatigue: does she have a sleep disorder?
AB  - A 13-year-old girl presented to our Division of Adolescent Medicine for
      evaluation of ongoing fatigue. She and her mother reported that 15 months
      earlier, when the patient was in the 7th grade, she started to be tired and
      "sleep all the time." They do not remember her being ill at that time; a test for
      mononucleosis was reportedly positive, but Epstein-Barr virus titers showed "old
      disease." She remained fatigued throughout 7th grade but attended school without
      falling asleep; however, she was too tired to do her work and had to attend
      summer school. The patient received home instruction in 8th grade and reported
      that on weekdays she slept from 1 AM to 11 AM with a nap from 4 to 8 PM and on
      weekends she slept from 3 AM to 1 PM without a nap.

PMID- 23162933
TI  - Adolescent with an abdominal mass.

PMID- 23162934
TI  - Takayasu disease associated with severe osteoporosis in a pre-pubertal female.

PMID- 23162935
TI  - Bilateral scrotal pain.

PMID- 23162936
TI  - Acute onset of nausea, difficulty walking, and eye "spots".

PMID- 23162937
TI  - "These cramps are holding me back!" A star basketball player with muscle cramps.

PMID- 23162938
TI  - Multiple visits for abdominal pain, constipation, and "I need a test for sexually
      transmitted diseases".

PMID- 23162939
TI  - New rash.

PMID- 23162940
TI  - An adolescent female with abdominal pain and chronic cough.

PMID- 23162941
TI  - A cheerleader with weight loss and amenorrhea.

PMID- 23162942
TI  - Could it be ... something other than PID?

PMID- 23162943
TI  - Weight down, bilirubin up/weight up, bilirubin down: the strange case of the
      malnourished adolescent.

PMID- 23162944
TI  - Heart-breaking obesity.

PMID- 23162945
TI  - A hairy situation.

PMID- 23162946
TI  - Severe hypernatremia in an adolescent with an eating disorder.

PMID- 23162947
TI  - Dizziness and bradycardia for investigation.

PMID- 23162948
TI  - An adolescent with abnormal uterine bleeding: an uncommon cause for a common
      complaint.

PMID- 23162949
TI  - A common presentation of a rare genetic disorder clinically mimicking primary
      myopathy.

PMID- 23162950
TI  - The Pentaconcept in skeletal tissue engineering. A combined approach for the
      repair of bone defects.
AB  - Tissue engineering has become a hot topic in modern medicine. Its application in
      a surgical setting, such as for the treatment of skeletal defects, still has to
      tackle some problems that might look simple at first sight, but need a well
      structured handling combining surgery and science, with in a central position the
      patient, who is both cell donor and receptor of the tissue engineered end
      product. To achieve this goal in a clinical setting, a five steps pathway is
      described and designated as the Pentaconcept, integrating all ingredients for
      successful reconstructive procedures.

PMID- 23162951
TI  - Relevance of World Health Organization surgical safety checklist to trauma and
      orthopaedic surgery.
AB  - Surgery like civil aviation is a risk-prone occupation. Civil Aviation has
      reported a death rate of less than 1 in a million exposures. On the other hand,
      surgery has a reported mortality rate of 100 per million surgeries. The National
      Reporting and Learning System (NRLS) database in England reported 152,017
      'incidents' occurred during 4.2 million surgeries in 2008. Trauma and orthopaedic
      surgery accounted for 32.4 percent of these 'incidents'. Wrong-site surgery
      occurred in a total of 133 patients, with an incidence of 31.6 per million
      surgeries. A system to implement and maintain safe surgical practice is mandatory
      to prevent these 'incidents'. The factors identified in the genesis of these
      incidents are errors in decision making, lack of communication, leadership and
      teamwork. These human errors can easily be prevented using a formal structured
      communication, like the checklists. In 2008, the WHO published a set of
      guidelines to ensure the safety of surgical patients. In 2009, the checklist was
      modified with an intention to reduce major surgical complications and was proved
      to be effective. Wrong level spinal surgery needs special emphasis. There may be
      an increasing role for checklists in Trauma and Orthopaedic surgical practice to
      improve its safety profile by being procedure-specific.

PMID- 23162952
TI  - Identification of adverse events in orthopaedic practice: a step towards quality
      care.
AB  - Adverse Events (AE's) are unintended injuries or complications resulting in
      death, disability or prolonged hospital stay, that arise from deficiency in the
      health care management. The objective of this retrospective study is to assess
      the incidence of AE's, its impact on patients in terms of morbidity and
      mortality. All orthopaedic patients admitted to the male orthopaedic ward between
      1st August 2010 to 31st July 2011, were included. Any such event that occurred in
      the index admission or within 30 days of discharge was included in the present
      study. Identification of AE's was based on the written records in case-sheet and
      analysis of the computer data. When clarification was required, the issue was
      discussed with involved physicians and nursing staff and the patient was
      contacted by telephone. Presence of one or more of the 12 predefined screening
      criteria constituted the screening process. Fifty three (10.83%) of 489 patients
      studied during the study period experienced a total of 101 AE's (20.65%).
      Majority of AE's occurred in trauma patients admitted from the emergency room--35
      (66%)--and from the outpatient department (OPD)--30 (56.6%)--. Of the 101 AE's,
      74 (73.1%) were estimated to have a high degree of preventability. On assessing
      the impact on patients, residual morbidity was noted in 1 (1.88%) patient. There
      was no mortality as a result of AE. AE's occurred due to non-adherence to
      existing protocols in totality. AE's resulted in increased morbidity of the
      patients, longer hospital stay, multiple surgeries and economic burden to the
      hospital. Identifying AE's provides the foundation and driving force for
      initiative to reduce morbidity. It also helps to evolve specific risk reduction
      strategies and self auditing and thereby improve quality care of patients.

PMID- 23162953
TI  - Management of proximal femoral fractures using the Ilizarov principles.
AB  - External fixation can be an exceptional relief solution in the treatment of
      proximal femoral fractures. We would like to share our experience using external
      fixation techniques with either the Ilizarov frame or Hofmann system in 23
      patients with complicated fractures.

PMID- 23162954
TI  - Rotator cuff tears in patients younger than 50 years of age.
AB  - The purpose of this study was to investigate the characteristics of rotator cuff
      tears and the clinical outcome of rotator cuff repair in patients under 50 years
      of age. Sixty-eight patients (72 shoulders) aged < 50 years, who underwent repair
      of rotator cuff tears were evaluated. We analyzed the cause of injury, tear size,
      time from symptom onset to surgery, and rate that patients returned to previous
      jobs and sports. Postoperative results were assessed by pain, strength, range of
      motion, and UCLA scoring system. Most of the injuries were caused by an
      unambiguous traumatic event. The tear size generally was medium or large, while
      the time from symptom onset to surgery was shorter than that seen in a mixed
      population. The postoperative outcomes generally were good to excellent, and the
      rate that patients returned to previous jobs and sports was high. The findings
      suggest that a good outcome after early repair in younger patients with traumatic
      rotator cuff tears can be expected.

PMID- 23162955
TI  - Nonunion of the radial neck following operative treatment for displaced radial
      head and neck fractures.
AB  - Nonunion of the radial neck is uncommon after operative treatment of displaced
      radial head and neck fractures. Treatment of nonunion of the radial neck remains
      a subject of debate and various treatment options have been introduced. This
      study presents six patients with nonunion of the radial neck following operative
      treatment for displaced radial head and neck fractures and the long-term clinical
      outcomes of conservative treatment for nonunion of the radial neck. Three hundred
      and twenty-six patients underwent operative treatment for displaced fractures of
      the radial head and neck from 1996 to 2008; six of these patients (1.8%)
      developed nonunion of the radial neck. No additional surgical treatment was
      undertaken after nonunion was confirmed. Time from primary operation to diagnosis
      of nonunion, clinical presentation, radial head-shaft angle, range of motion and
      residual angulations on plain radiographs were documented. Functional outcomes
      were evaluated using the Mayo elbow performance index (MEPI) at final follow-up
      visit. Average time from primary operation to diagnosis of nonunion was 10.2
      months. Five patients reported no functional deficits and no clinical discomfort
      when nonunions were confirmed. Another patient complained of mild elbow
      discomfort only when lifting heavy weights. All patients achieved satisfactory
      clinical outcomes after an average follow-up of 7.6 years. Regardless of
      radiological findings, no further surgical treatment is recommended for
      asymptomatic nonunion of the neck of the radius.

PMID- 23162956
TI  - Residual wrist pain after volar locking plate fixation of distal radius
      fractures.
AB  - A prospective multicenter clinical study evaluated, using the Hand20 and hand
      diagram, the disability, incidence, location, and predictive factors of residual
      wrist pain 18 months after volar locking plate fixation of distal radius fracture
      in 122 patients. The average Hand20 score and numeric rating scores for pain were
      13.1 +/- 18.2 and 2.1 +/- 23, respectively. Fifty-seven patients indicated that
      they had pain. Among those patients, 25 had ulnar pain and 45 had radial pain.
      The incidence of radial-sided wrist pain was higher than ulnar-sided wrist pain.
      Logistic regression analysis showed that female sex and intra-articular fracture
      significantly correlated with radial-sided wrist pain. Volar locking plate
      fixation maintained anatomical reduction; however, a significant number of
      patients complained of residual wrist pain.

PMID- 23162957
TI  - Paediatric acetabular fractures. Data from the German Pelvic Trauma Registry
      Initiative.
AB  - The aim of this study was to present an analysis of acetabular fractures during
      childhood as compared to those in adults. Within a multicenter register study,
      data of 3 time periods (1991-93, 1998-2000, 2004-2008) were pooled and analyzed
      for incidence, epidemiology, classification, outcome and treatment of acetabular
      fractures in children (< 15 years). One hundred fifty three children (2.1%) among
      7360 patients with pelvic fractures were included in the study. Only 15 children
      sustained an acetabular fracture (9.8%). Simple fracture types according to
      Letournels' classification were more frequent in paediatric patients (p < 0.01),
      receiving less often operative treatment. Multiple injuries were present in 36%
      of children, the average Injury Severity Score (ISS) of all children was 17
      points. Clinical results were good with an average Merle d'Aubigne score of 16.4
      points and a Karnofsky performance of 90%. Fractures of the acetabulum in
      childhood remain a rare injury with distinct fracture characteristics, usually
      caused by high impact accidents.

PMID- 23162958
TI  - Multi-modality imaging of transient osteoporosis of the hip.
AB  - Transient osteoporosis of the hip (TOH), also referred to as bone marrow edema
      syndrome (BMES) of the femoral head and neck, is an uncommon and therefore
      underdiagnosed benign skeletal disorder, affecting primarily women, particularly
      in their last trimester of pregnancy, and middle-aged men. The disease is
      characterized by self-limiting hip pain and radiographically evident osteopenia,
      but these radiographic findings can sometimes be delayed. In the early phase, the
      main diagnostic dilemma lies in differentiating TOH from osteonecrosis of the
      femoral head (ONFH). Conventional radiographs, Tc-99m bone scans (multiphase,
      SPECT or SPECT/CT) and MRI scans from 10 male patients with 12 TOH episodes were
      retrospectively and independently reviewed by two nuclear medicine physicians and
      a musculoskeletal radiologist. The purpose was to identify a typical imaging
      pattern, and secondly, to reliably distinguish TOH from ONFH. In the early phase
      of TOH, conventional radiography of the hip could not sufficiently detect focal
      osteopenia. But in all 10 patients (mean age 45 years, range, 34-62), bone scans
      and MRI scans demonstrated a similar pattern of diffuse hyperaemia, bony uptake,
      and bone marrow edema in the femoral head and neck, extending to and ending with
      a sharp demarcation at the intertrochanteric region. Additionally, neither SPECT
      nor SPECT/CT nor MRI revealed any cold area or crescent-shaped subchondral defect
      in the femoral head, indicating ONFH. In some cases there was a joint effusion in
      varying degree. In 9 patients, an uneventful recovery was eventually observed.
      Scintigraphically diffuse hyperaemic and/or homogeneous osseous uptake in femoral
      head and neck extending to the intertrochanteric region, as well as the recently
      introduced term transient bone marrow edema syndrome (BMES) of the hip on MRI,
      are probably both expressions of the same pathophysiological mechanism, and
      pathognomonic for TOH. Hopefully, recognizing this highly specific imaging
      pattern will exclude in the future more aggressive skeletal diseases like ONFH,
      severe arthritis, osteomyelitis or even malignancy.

PMID- 23162959
TI  - Expectations and outcome of a scientifically developed hip prosthesis in 170 hips
      with a follow-up of 5-12 years.
AB  - Roentgen stereophotogrammetric analysis (RSA) is commonly used to assess
      prosthetic stability as a predictor of the long-term clinical outcome of new
      total hip systems. Although the RSA technique is very accurate, it may not be
      trivial to interpret migration rates into clinical outcome, as critical migration
      rates depend heavily on the design of the prosthesis. In the present study we
      describe the clinical results of the Scientific Hip Prosthesis (SHP), which had
      unexpectedly high migration values in a clinical RSA study. We evaluated the
      clinical results of a single surgeon study consisting of 170 hips with a follow
      up of 5-12 years (mean: 83 years). The survival rate was 98.8% at ten years for
      aseptic loosening of the stem. This study therefore indicates that a prosthetic
      design may function clinically rather well although relatively high migration
      rates have been reported. The prediction of clinical survival of new prosthetic
      components remains a challenging task and the interpretation of migration rates
      with new designs should be considered with much caution.

PMID- 23162960
TI  - The lateral tibial tunnel: does it allow for adequate fixation in ACL surgery?
AB  - The purpose of this cadaver study about the ACL graft was to compare a "Lateral
      Tibial Tunnel" (LTT) and a "classic, anteroMedial Tibial Tunnel" (MTT), as to
      fixation strength and mode of failure. Ten pairs of fresh frozen human proximal
      tibias were used. In one of both tibias a classic anteromedial tunnel was used,
      versus a lateral tibial tunnel in the contralateral knee. Autologous doubled
      semitendinosus and gracilis tendons were fixed in the tunnels. A maximum load to
      failure test was performed to determine the stiffness and the strength of the
      graft-tibia complex. CONCLUSION: for none of the measurements was there any
      significant difference between both tunnels. The tibial fixation strength of a
      human autologous doubled hamstring graft in ACL surgery is similar, whether a
      lateral or an anteromedial tibial tunnel is used. This is the first study
      investigating fixation strength of an ACL graft in a lateral tibial tunnel.

PMID- 23162961
TI  - Survival of autologous osteochondral grafts in the knee and factors influencing
      outcome.
AB  - The primary aim of this retrospective study was to determine the medium-term
      survival of autologous osteochondral grafts (mosaicplasty) in the knee. The
      secondary aims were to evaluate any reason for failure, and to ascertain if age,
      gender, BMI, previous or associated knee surgery, site or size of the
      osteochondral graft had any influence on outcome. Fifty-five patients undergoing
      an autologous osteochondral graft procedure between 1999 and 2008 were evaluated,
      with a mean follow-up of 5.9 years (range 0.5 to 10.5). Loosening, graft
      degeneration or subsequent surgery in the form of arthroplasty, revision
      autologous osteochondral graft or any other osteochondral procedure, and an
      Oxford knee score above 49.7 (see text) were considered as failure. Kaplan-Meier
      analysis demonstrated an 87.5% survival at 8 years (95% CI 72% to 97%). The mean
      Oxford score at follow-up was 163% (95% CI 10.6% to 22.1%) at follow-up. Two of 6
      failures occurred in patients with varus malalignment. Linear regression analysis
      demonstrated an improved outcome in Oxford knee score in younger patients.
      Gender, BMI, previous or associated knee surgery, site and size of the graft had
      no influence on outcome. The authors consider autologous osteochondral grafting
      as a reliable method of treatment in the medium-term for young patients with
      small contained articular cartilage lesions up to 4 cm2. Careful attention should
      be paid to the mechanical axis (varus) prior to grafting. Long-term studies are
      necessary.

PMID- 23162962
TI  - A comparison of external fixation alone or combined with intramedullary nailing
      in the treatment of segmental tibial defects.
AB  - The purpose of this study was to compare the results of external fixation alone
      versus external fixation combined with intramedullary nailing in the
      reconstruction of segmental defects of the tibia resulting from chronic
      osteomyelitis. Thirty-two patients were treated with external fixation alone and
      17 patients with the combined technique. Surgical reconstruction utilised
      distraction osteogenesis by focal segment transport after infection was
      eradicated. In the external fixation group, the mean size of the defect was 724
      cm, external fixation index was 56.32 days/cm and consolidation index was 40.09
      day/cm. In the combined technique group, the mean size of the defect was 8.89 cm,
      external fixation index was 1631 days/cm and consolidation index was 25.7
      days/cm. There was no difference in non-union, deformity, limb length discrepancy
      (LLD), bone and functional results. However, there was a higher rate of
      reinfection in the combined group when tibial lengthening exceeded 9.25 cm and
      lengthening ratio was more than 24.8%.

PMID- 23162963
TI  - Plate fixation of paediatric fractures of the distal tibia and fibula.
AB  - The role of surgery in the management of paediatric long-bone shaft fractures
      remains a matter of debate. We present a series of paediatric patients with
      unstable fractures of the distal tibia and fibula, treated with titanium plate
      fixation. Excellent results were obtained after plate fixation.

PMID- 23162964
TI  - Vitamin D: a poor screening tool for biochemical and radiological rickets.
AB  - This retrospective study aims to determine if a relationship exists between serum
      25-hydroxyvitamin D level and the diagnosis of biochemical or radiological
      rickets in children with bone and joint pain, muscle fatigue or varus/valgus
      knees. A retrospective biochemistry database and case note study was undertaken
      on 115 new patients referred to the senior authors' elective Paediatric
      Orthopaedic Clinic in 2010. Their mean age was 10.95 years (95% CI 10.24-11.68).
      Mean serum vitamin D was 18.27 mcg/l (95% CI 16.13-20.41), while 30 mcg/l is the
      normal threshold. One hundred and three children (88%) had vitamin D levels below
      normal. Winter/springtime blood samples were more likely to be deficient and this
      was statistically significant. Three Asian females (2.61%) were diagnosed with
      radiological rickets. Vitamin D levels below normal are common in children
      presenting with vague limb or back pain, but this rarely presents with
      biochemical or radiological rickets. Serum vitamin D level is not a suitable
      screening tool for biochemical or radiological rickets. Vitamin D requirement in
      children is unclear and requires further study.

PMID- 23162965
TI  - Low back complaints worse, but not more frequent in subjects with congenital
      lumbosacral malformations: a study on 5000 recruits.
AB  - The authors studied the plain radiographs and medical records of 5000 military
      recruits, mean age 19.1 years (range: 18 to 22), screened in a Turkish Military
      Hospital in the period November 2008-October 2009. They focused on the incidence
      of congenital lumbosacral malformations, such as spina bifida occulta and
      transitional vertebra, trying to find a correlation with subsequent low back
      complaints. Only 80 out of 748 subjects (10.7%) with low back complaints had one
      or more malformations, versus 744 out of 4252 subjects (17.5%) without low back
      complaints. This pleaded against a correlation between malformations and low back
      disorders. Also the literature is completely divided as to this problem, which
      means that there is probably no correlation at all. Interestingly, the 80
      subjects with low back complaints and malformation estimated their pain level at
      +/- 4.6 on a Visual Analog Scale for pain, while the 668 with low back complaints
      but without malformation estimated their pain level at only +/- 2.2 (p = 0.007).
      At least two other studies led to the same conclusion. This paradox might be due
      to the fact that congenital malformations concentrate all external stress on the
      adjacent levels.

PMID- 23162966
TI  - Unilateral laminotomy with bilateral decompression for lumbar spinal stenosis:
      short-term risks in elderly individuals.
AB  - The aim of this retrospective study was to compare the short-term (4 weeks)
      surgical complications after unilateral laminotomy for bilateral decompression
      (ULBD) in patients with lumbar spinal stenosis, below and above age 65. Twenty
      nine consecutive patients operated upon in 2011 were included: 12 below age 65,
      and 17 above age 65. Five complications (17.1%) were observed, all in the older
      age group: 3 dural tears, one root injury, and one subcutaneous collection
      requiring re-operation. The difference between groups was not statistically
      significant (p = 0.0521). Moreover, comparable or higher complication rates were
      noted after alternative techniques. The CRP level, obtained one day
      postoperatively, was lower than after alternative procedures, pleading for the
      limited invasiveness of ULBD. Old age seems to be associated with slightly
      elevated rates of short-term surgical complications, but without an increment in
      morbidity. Unilateral laminotomy for bilateral decompression does not carry an
      excessive risk in the elderly population.

PMID- 23162967
TI  - Achilles tendon allograft with its bony attachment to repair rupture and
      extensive degeneration of the heel cord.
AB  - An Achilles tendon allograft with its bony calcaneal attachment was successfully
      used to repair a spontaneous rupture of a severely degenerative and irreparable
      Achilles tendon. After 18 months of follow-up, the patient is satisfied and the
      Achilles tendon power has returned to a normal level.

PMID- 23162968
TI  - Beware the syndrome in neonatal hip instability: follow up assessment is required
      after apparent resolution.
AB  - Developmental dysplasia of the hip is one of the most common congenital
      musculoskeletal disorders of childhood, affecting 1-3% of newborns. An early
      diagnosis and prompt treatment is essential to avoid complex treatments and
      achieve improved results. Since 1992, we have undertaken a screening programme
      for clinical instability and at risk patients. During this time, there have been
      only two cases which have been normal on both clinical, and, static and dynamic
      ultrasound assessment, that have subsequently deteriorated. In these two cases
      there was an underlying syndrome associated with hyperlaxity, which behaves
      unpredictably compared to 'true' developmental dysplasia of the hip. In
      conclusion, if a hip has been referred as unstable but it is found to have a
      primary syndromal cause (especially if hyper lax) with sonographically normal
      hips at one to two weeks of age, it is best to review clinically and
      sonographically at 6 weeks and 3 months of age to confirm that the hip is
      maintaining stability.

PMID- 23162969
TI  - There may be a role for hyperbaric oxygen therapy in transient osteoporosis of
      the hip.
AB  - Transient osteoporosis of the hip (TOH) is a rare clinical condition with usually
      an unknown aetiology and which typically develops in middle-aged men, or in women
      in the third trimester of their pregnancy. It is characterized by transient
      osteopenia and by gradually increasing pain associated with a limitation of the
      range of motion of the hip. Bone marrow oedema is a typical but nonspecific
      finding in TOH. A 33-year-old female patient presented with severe hip pain one
      month after delivery. Her history was unremarkable except for a Hashimoto's
      Disease of 8 years' duration. Magnetic resonance imaging (MRI) showed significant
      bone marrow oedema with increased signal intensity in the femoral head on T2
      weighted images. A diagnosis of TOH was made and the patient received a total of
      30 sessions of hyperbaric oxygen (HBO) at 2.4 ATA, 2 hours each, in a multiplace
      chamber. Over the course of HBO treatment, her pain was gradually relieved and
      she became asymptomatic after one month together with a complete recovery of the
      range of motion of the hip. MRI of the hips 10 weeks after onset of HBO therapy
      showed normal signal intensity on T2-weighted images.

PMID- 23162970
TI  - Internal fixation of a traumatic fracture around a hip resurfacing arthroplasty
      using the proximal femoral locking compression plate.
AB  - We report on a 40-year-old man who sustained a traumatic extracapsular fracture
      of the proximal femur with a Birmingham Hip Resurfacing in situ. It was decided
      to retain the resurfacing implant and a proximal femoral periarticular locking
      compression plate (Synthes) was used to stabilise the fracture. The patient
      regained full range of pain-free movement, and was bearing his full weight on the
      operated leg by 18 weeks. He had a Harris Hip score of 90. Fractures around hip
      resurfacing arthroplasties are an emerging problem, and a literature review
      reveals two distinct modes of presentation i.e. 'atraumatic' and 'traumatic'
      fractures. We elaborate on these two different fracture patterns, with emphasis
      on the epidemiology, biomechanical considerations, and management strategies for
      the 'traumatic' type of periprosthetic fracture.

PMID- 23162971
TI  - Glomus tumour eroding the medial facet of the patella: a case report.
AB  - Glomus tumours are benign lesions occurring essentially in the hand, with a
      predilection for the subungueal area. Even though they have been reported in
      literature, extradigital localisations of glomus tumours are frequently
      misdiagnosed; they never lead to bone osteolysis. We report the case of a patient
      who presented with a typical patellofemoral syndrome due to a glomus tumour that
      eroded the medial facet of the patella. MRI, which is the gold standard for the
      diagnosis, showed a well-delineated spherical tumour with enhancement after
      Gadolinium injection. CT Scan excluded an osteoid osteoma and showed the erosion
      of the patella. The lesion was surgically resected and the histological
      examination established the definitive diagnosis.

PMID- 23162972
TI  - Your opportunity to effect change.

PMID- 23162973
TI  - Lansley and Milton out...and Hunt to be new health secretary.

PMID- 23162974
TI  - Cot death rates continue to fall.

PMID- 23162975
TI  - Quality first: are we expecting too much from the regulator?

PMID- 23162976
TI  - The real cost of eating disorders.

PMID- 23162977
TI  - Health visiting: celebrating 150 years of public health.

PMID- 23162978
TI  - A concept analysis of motivational interviewing for the community practitioner.
AB  - This article will be of interest to school nurses, health visitors, student
      health visitors and their practice teachers. An opportunity is taken to explore
      the concept of motivational interviewing for community practitioners, to
      demystify the technique. Guided by Walker and Avant's framework for concept
      analysis, the article explores if practitioners are already using a motivational
      interviewing approach, how this way of working can be effective and how to
      develop this useful communication skill to evoke and strengthen personal
      motivation for change. Key terms such as 'agenda matching' and 'change talk' are
      applied to case scenarios to add meaning to the exploration. Details of further
      resources are also provided.

PMID- 23162979
TI  - Diabetes screening as part of a vascular disease risk management programme.
AB  - Type 2 diabetes mellitus is a growing public health concern worldwide. There is
      the potential to prevent type 2 diabetes mellitus by lifestyle interventions
      including increased physical activity, dietary modification and weight reduction
      in the obese therefore screening for diabetes can be beneficial. This case study
      discusses two methods used for diabetes screening as part of a population wide
      vascular risk management programme in an island community off the west coast of
      Scotland. The programme was delivered to individuals aged 40 to 79 years who met
      the inclusion criteria using a combined service delivery model including a
      multifunctional mobile unit across a remote and rural location. The change from
      using random plasma glucose to using the haemoglobin A(1c) (HbA(1c)) assay
      improved recommended follow rates for patients with a positive screen and reduced
      the burden on primary care and the hospital laboratory.

PMID- 23162980
TI  - The recognition and management of isolated cleft palate.
AB  - Cleft palate in the absence of a cleft lip (i.e. isolated cleft palate) causes
      upset for parents whenever it is diagnosed; however, delayed diagnosis at over 24
      hours of age can cause increased distress due to feeding difficulties and fear of
      what else could have been missed. One third of cleft palates are not recognised
      within 24 hours of delivery. Considerable effort is being made to ensure early
      diagnosis following delivery, by raising awareness of midwives, neonatologists
      and paediatricians of the need to visualise the whole palate including the uvula,
      and through changes to the Newborn Screening Programme. Community practitioners
      including health visitors and school nurses are ideally placed to recognise key
      feeding and speech features associated with cleft palate, and then to refer to
      one of the nine regional cleft teams (England and Wales). There is a managed
      clinical network in Scotland, and there are also centres in Northern Ireland and
      Eire. Multidisciplinary cleft care commences in conjunction with local health
      services following referral to the regional specialist team.

PMID- 23162981
TI  - Preventing type 2 diabetes: a role for every practitioner.
AB  - Type 2 diabetes accounts for approximately 90% of the three million people who
      have diabetes in the UK, and it presents a significant challenge to the NHS. The
      number of people developing the condition is rapidly increasing, and it is
      estimated that five million people will have diabetes by 2025. Diabetes can lead
      to the development of a number of disabling and costly complications including
      blindness, kidney failure, heart disease, stroke and amputation. Type 2 diabetes
      is treated by improvements in lifestyle, losing weight, treatment with a number
      of oral medications and, eventually, injection therapy including insulin. The
      increasing number of people with diabetes means it is a significant consumer of
      NHS resources. The development of type 2 diabetes is associated with a number of
      risk factors. There is strong and consistent evidence which shows that early
      detection of people at high risk followed by changes in lifestyle can reduce the
      incidence of type 2 diabetes and its complications, eg: diabetes. New guidance
      from the National Institute for Health and Clinical Excellence (NICE) on
      identifying people at high risk of developing type 2 diabetes and the provision
      of clinically and cost effective interventions to prevent or delay the onset of
      the condition has recently been published. This article summarises the guidance
      and particularly focuses on the role of nurses working in primary and community
      care settings.

PMID- 23162982
TI  - A project to improve uptake of immunisation in north-east London.

PMID- 23162983
TI  - Can a 'sign-off' experience with the health visiting service benefit students?

PMID- 23162984
TI  - Learning from Experience project: improving the process of internationally
      educated nurses' applications for registration.

PMID- 23162985
TI  - Emergency room closures.

PMID- 23162986
TI  - Survey draws attention to HYDROmorphone knowledge deficits.

PMID- 23162987
TI  - Preventing chronic disease one child at a time. Linking brain health to
      population health: what nurses need to know.

PMID- 23162988
TI  - Have you missed signs in a victim of strangulation?

PMID- 23162989
TI  - A day in the life of a nurse practitioner.

PMID- 23162990
TI  - When a nurse becomes a patient: the undercover story.

PMID- 23162991
TI  - Laughter.

PMID- 23162992
TI  - Managing change.

PMID- 23162993
TI  - Donating bone marrow: a day on the other side of the wire.

PMID- 23162994
TI  - Infection control in operating theatres.
AB  - The operating theatre complex is the heart of any major surgical hospital. Good
      operating theatre design meets the functional needs of theatre care
      professionals. Operating theatre design must pay careful consideration to traffic
      patterns, the number and configuration of nearby operating rooms, the space
      required for staff, administration and storage, provisions for sterile processing
      and systems to control airborne contaminants (Wan et al 2011). There have been
      infection control issues with private finance initiative built operating theatres
      (Unison 2003, Ontario Health Coalition 2005). The aim of this article is to
      address these issues as they relate to infection control and prevention.

PMID- 23162995
TI  - Perioperative management of chronic respiratory disease.
AB  - Respiratory disease contributes significantly to the perioperative challenges of
      surgery. Preexisting pulmonary co-morbidities and respiratory complications can
      have profound effects on patient outcomes. Knowledge of these conditions and the
      potentially deleterious effects of anaesthesia and surgery can enable clinicians
      to optimise lung function, reduce complications and improve results.

PMID- 23162996
TI  - Topical negative pressure therapy: current concepts and practice.
AB  - Research into topical negative pressure therapy (TNPT) started in 1989 with Dr
      Louis Argenta and Prof Michael Morykwas of Wake Forest University School of
      Medicine in North Carolina, USA. In 1997, Morykwas and Argenta concluded that
      TNPT both enhanced granulation tissue formation and helped bacterial clearance,
      through the actions of negative pressure Armstrong and Lavery confirmed this in
      2005, concluding that TNPT therapy was promoting the development of granulation
      tissue. Numerous other studies have proved that TNPT is beneficial for a myriad
      of other wounds including: sternotomy wounds, extensive de-gloving injuries,
      various soft tissue injuries prior to surgical closure, skin grafting, pressure
      sores, leg ulcers, sacral pressure ulcers, acute traumatic soft tissue defects,
      and soft tissue defects following rigid stabilisation of lower extremity
      fractures. This review aims to summarise the clinical and scientific concepts of
      TNPT and its future applications.

PMID- 23162997
TI  - Difficulties in intraoperative care.
AB  - Difficult situations which occur intraoperatively have a direct impact on nurses
      working within the area. A study was undertaken focusing nurses' confrontations
      with difficult situations where the narrations from twelve nurses were taped. A
      phenomenological method was used to analyse this information and revealed how
      difficult intraoperative situations arise and how the nurses found different ways
      of handling these situations.

PMID- 23162998
TI  - Richard von Volkmann: Volkmann's ischaemic contracture.
AB  - In the German surgical journal Zentralblatt fur Chirurgie of 1881, Richard von
      Volkmann wrote; 'The paralyses and contractures that follow tightly applied
      bandages, chiefly in the forearm and hand, and less often in the lower extremity,
      are to be viewed as ischemic. They arise from the arterial supply being
      interrupted for too long'. The article then goes on to state; 'contractures of a
      similar nature also appear after ligatures, avulsions and contusions of large
      vessels'.

PMID- 23162999
TI  - Mental health services.

PMID- 23163000
TI  - Implementation framework for last year's mental health strategy.

PMID- 23163001
TI  - Fighting for their rights.

PMID- 23163002
TI  - Winning the mental battle.

PMID- 23163004
TI  - New legislation and the Paralympic legacy.

PMID- 23163003
TI  - Strategic thinking.
AB  - The new framework is seen as a positive move to improve the nation's mental
      health and wellbeing. However, despite the strategy highlighting the needs of
      people with learning disabilities, the framework offers very little specifically
      for this group. This raises concern that this group will remain off the radar for
      those in mainstream services and organisations that could support them to
      maintain their mental health and wellbeing. With the Valuing People Now team
      disbanded, there is no nationally-accredited body given the role to champion
      people with learning disabilities. Those with a learning disability and a mental
      illness should be able to access services and be treated in the same way as
      anyone else with reasonable adjustments being made in accordance with the
      Disability Discrimination Act (2005) and the Disability Equality Duty (2006). But
      as the implementation framework is lacking in attention to this group more work
      will be required by mainstream and specialist organisations to ensure the key
      messages from the frameworks are applicable to people with learning disabilities.

PMID- 23163005
TI  - Independent mental health advocacy.

PMID- 23163006
TI  - A Scottish mental health arts festival.

PMID- 23163007
TI  - The complexity of the issues faced by the Court of Protection in relation to
      mental capacity decisions.

PMID- 23163008
TI  - Harm-minimisation for self-harm.

PMID- 23163009
TI  - Possible implications of recent research into the gut-brain axis on people with
      mental health problems.

PMID- 23163010
TI  - NSUN's new scheme to ensure mental health service users are at the heart of the
      new health and social care system.

PMID- 23163011
TI  - The right to be heard: independent mental health advocacy services in England.

PMID- 23163012
TI  - Turning the tables.

PMID- 23163013
TI  - Looking at ordinary people's tales of living with their mental illness. Interview
      by Dan Parton.

PMID- 23163014
TI  - Right there all along. Latest IOM report lays out how to deliver safer, more
      effective care by using existing strategies, technology.
AB  - Want to make healthcare safer and more cost-effective? You already have the
      necessary tools, a new IOM report says. "To Err is Human made visible the
      tremendous problem we had with medical errors, but back then very few systems had
      this kind of data infrastructure," says Paul Tang, of the Palo Alto (Calif.)
      Medical Foundation. said. "We're in a much different spot now."

PMID- 23163015
TI  - The case for collaboration. Government should follow private sector: economists.

PMID- 23163016
TI  - Ascension gets bigger. Marian deal aims to position both for reform.

PMID- 23163017
TI  - Medicaid battleground. Maine challenges expansion, citing coercion.

PMID- 23163018
TI  - VA gets local for mental health.

PMID- 23163019
TI  - Credit concerns. Report: New Mass. law may hurt hospital margins.

PMID- 23163020
TI  - Big debate on short-term stays.

PMID- 23163021
TI  - Targeting constitutionality. Providers going to court over state CON laws.

PMID- 23163022
TI  - Cost comparison. One document gives healthcare better bang for the buck.

PMID- 23163023
TI  - The day we lost a corpse. Put institution's values first, even if it means
      revealing a troubling incident.

PMID- 23163024
TI  - Where everyone is a caregiver. Patient-centered approach earns Tennessee system
      annual national quality award.

PMID- 23163025
TI  - Deleting delirium. Hospital uses IT to help identify at-risk patients.

PMID- 23163026
TI  - [Study of prevalence of rare and difficult to cultivate causative agents of
      inflammatory diseases of respiratory organs].
AB  - AIM: Study the prevalence of Mycoplasma pneumoniae, Chlamydophila pneumoniae,
      Chlamydophila psittaci, Legionella pneumophila, Moraxella catarrhalis,
      Cytomegalovirus, Herpes simplex I/II virus (HSV I/II) in individuals of various
      age groups with varying inflammatory broncho-pulmonary diseases. MATERIALS AND
      METHODS: 384 adults and 1001 children with clinically confirmed diagnoses were
      examined by PCR method: community-acquired pneumonia, acute bronchitis, bronchial
      asthma, ARD/ARVD, as well as 127 healthy children and 52 healthy adults. Sputum,
      smears from posterior fornix of pharynx, blood, saliva from children of the first
      year of life were used as material for the study. RESULTS: Wide prevalence of M.
      pneumoniae and C. pneumoniae among adults and M. pneumoniae among children older
      than 1 year with inflammatory diseases of respiratory organs was established. C.
      psittaci, L. pneumophila, M. catarrhalis occurred in isolated cases in both
      adults and children. Active replication of herpes group viruses was detected in
      patients of all age groups with inflammatory broncho-pulmonary diseases, and in
      children Cytomegalovirus replication predominated, in adults--HSV I/II.
      CONCLUSION: High frequency of prevalence of M. pneumoniae and C. pneumoniae in
      inflammatory diseases of respiratory tract was established, giving evidence of
      reasonability and necessity of examination of patients with various nosologic
      forms of diseases for these species of microorganisms with the aim of effective
      etiotropic therapy.

PMID- 23163027
TI  - [Features of etiologic structure and factors of persistence of bacteria isolated
      during infection of lower urinary tract and chronic bacterial prostatitis].
AB  - AIM: Evaluate microbial specter and factors of persistence in facultative
      anaerobic bacteria isolated from urine during infection of lower urinary tract
      (ILUT) and secretion of prostate gland (SPG) during chronic bacterial prostatitis
      (CBP). MATERIALS AND METHODS: Bacteriologic study of urine from 144 women (group
      I) during exacerbation of uncomplicated ILUT and SPG of 105 patients with CBP
      (group II) was carried out. Quantitative and qualitative composition of
      microflora as well as adhesive (AA) and anti-lysozyme (ALA) activity for entero-,
      coryneformic bacteria and hemolytic staphylococci was determined. RESULTS: In
      groups I and II aerobic-anaerobic associations with domination of non-clostridial
      anaerobic bacteria, coagulase-negative staphylococci (CNS), coryneformic
      bacteria, for urine--enterobacteria were isolated from urin and SPG. S.
      haemolyticus strains predominated in the CNS group. In group I the frequency of
      detection of strains of enterobacteria and S. haemolyticus with high AA and ALA
      were higher (p < 0.05) compared with corynebacteria. In group II cultures of S.
      haemolyticus more frequently (p < 0.05) had AA and ALA compared with entero- and
      corynebacteria. CONCLUSION: In etiologic structure of ILUT and CBP a tendency of
      shift of gram-negative flora to gram-positive is observed. Detection of AA and
      ALA in most of the S. haemolyticus and coryneformic bacteria gives evidence of
      their pathogenic and persistence potential.

PMID- 23163028
TI  - [Clinical course of acute respiratory infection and the state of microbiocenosis
      of upper respiratory tract in pregnant women].
AB  - AIM: Evaluate clinical features of the course of acute respiratory infection
      (ARI) and the state of microbiocenosis of nasopharynx of pregnant women at
      gestational term of 14 - 26 weeks. MATERIALS AND METHODS: At the stage of
      outpatient therapy of ARI 49 pregnant women at the gestational term of 14 - 26
      weeks were examined: group 1--27 individuals consulting at day 1 and receiving
      Viferon (gel) intranasally for 10 days, group 2--22 individuals consulting at day
      2 - 3 and receiving Viferon (gel and suppositorium). Respiratory viral infection
      was diagnosed by multiplex PCR. Bacteriologic study of discharge from the middle
      section of the pharynx was performed by the standard technique. RESULTS: ARI in
      group 1 of pregnant women were regarded as mild severity and persisted for an
      average of 3 days. In group 2 in 13 (59%) of patients ARI of moderate severity
      was noted and the recovery occurred at day 6. Pyo-inflammatory diseases of ENT
      organs appeared in 10 (45.4%) of patients. Respiratory infections were determined
      in 16 (32.7%) of them: coronaviruses--in 5 (10.2%), rhinoviruses--in 3 (6.2%),
      respiratory syncytial viruses--in 6 (12.3%), parainfluenza (type 2) and influenza
      A viruses--1 (2%) both, without significant differences between the observed
      groups. Streptococcus agalactiae, Staphylococcus aureus, Streptococcus mitis,
      Moraxella catarrhalis, Corynebacterium spp., Streptococcus pyogenes with the
      predominance of the latter in 36.7% and 60% of cases, respectively, in pregnant
      women of the group 2 (p < 0.01), were detected in the microflora of the mucous
      membrane of the nasopharynx. CONCLUSION: Viferon preparation therapy prescribed
      at day 1 of outpatient visit of pregnant women may promote mild course o fARI and
      prophylaxis of complications of upper respiratory tract.

PMID- 23163029
TI  - [Systemic endotoxinemia as a pathogenetic factor of pregnancy complication].
AB  - AIM: Evaluation of the role of hemocirculation of a bacterial endotoxin in
      pregnancy complicated with gestosis. MATERIALS AND METHODS: A complex clinical
      laboratory examination of 74 pregnant women at the II-III trimester of
      gestational period including determination of serum cytokine levels (TNFalpha, IL
      1beta, IL-2, IL-4, IL-6, IL-8, IL-10, IFNgamma), C-reactive protein, LPS, LPS
      binding protein and IgG against R-core LPS in blood plasma was performed.
      RESULTS: In pregnant women with gestosis an increase in endotoxinemia level (p <
      0.0001), twofold increase in IgG titers against R-core LPS (p < 0.01) and an
      increase in LBP concentration by 14% (p < 0.05) without an increase in
      concentration of C-reactive protein were shown. Cytokine profile in gestosis was
      characterized by a twofold statistically significant increase of IL-1beta (p <
      0.0001), IL-8 (p < 0.0001) pro-inflammatory cytokine levels, a tendency of IL-6
      (p = 0.063), TNFalpha (p = 0.13) increase and a decrease of Th1 cytokine
      concentrations: IL-2 - by 6.5 times (p < 0.0001), IFNgamma--by 2 times (p <
      0.0001). CONCLUSION: The results allow to consider gestoses as a manifestation of
      increased endotoxin translocation into systemic blood flow during gestation, that
      determines the necessity to improve therapeutic measures in this pathology.

PMID- 23163030
TI  - [Primary causative agents of infectious complications in injured with severe
      trauma].
AB  - AIM: Study etiologic structure of infectious complications in injured with severe
      trauma. MATERIALS AND METHODS: Retrospective analysis of results of therapy
      outcomes in 5966 wounded and injured (1999 - 2009) and prospective observation of
      142 injured (2008 - 2009) by using epidemiologic, statistical and microbiological
      methods was carried out. RESULTS: Frequency of isolation and specific weight of
      causative agents depending on localization of infectious complication was
      established. Among 11486 isolated microorganism strains 4 causative agents
      dominated: Klebsiella pneumoniae, Pseudomonas aeruginosa, Acinetobacter spp. and
      Staphylococcus aureus. The proportion of these causative agents differed in
      various years. Interconnections of microorganisms composing associations were
      determined. CONCLUSION: Conduction of microbiological monitoring is determined by
      the necessity of constant control for leading causative agents of infectious
      complications in injured with severe trauma in the dynamic of their therapy.

PMID- 23163031
TI  - [Presence of genes of genotoxin associated with pks pathogenicity island in
      Escherichia coli M-17 probiotic strain].
AB  - AIM: Study the presence of genetic determinants of pks pathogenicity island
      containing clb (colibactin) genes in bacteria of the E. coli M-17 production
      strain by using PCR. MATERIALS AND METHODS: E. coli M-17 cultures isolated from
      biopreparations bificol (Microgen) and colibacterin (Biomed) and control strain
      obtained from Tarasevich State Institute on Standardization and Control (Moscow)
      were studied. Detection of genetic markers of colibacterin was performed by using
      multiplex PCR with 4 pairs of primers amplifying the main clb genes: clbB, clbN,
      clbA and clbQ, generating 575, 711, 981 and 820 bp amplicons, respectively.
      RESULTS: In genome of all the studied E. coli M-17 strains clbB, clbN, clbA and
      clbQ genes associated with the formation of genotoxic colibacterin were detected.
      CONCLUSION: Genome of E. coli M-17 bacteria used for production of probiotic
      preparations colibacterin and bificol contains genetic determinants ofgenotoxin
      that require further studies in terms of evidence of harmlessness of production
      bacteria.

PMID- 23163032
TI  - [Study of possibility of formation of Vibrio parahaemolyticus pandemic clones
      based on retrospective PCR-screening of clinical strains].
AB  - AIM: PCR-genotyping of Vibrio parahaemolyticus strains that had caused sporadic
      diseases in Novorossiysk from 1973 to 1976. MATERIALS AND METHODS: 24 clinical
      strains of V. parahaemolyticus isolated in Novorossiysk, most of which belonged
      to serogroups O4:K12 and O4:K8; 10 O3:K6 strains--causative agents of
      gastroenteritis outbreak in Vladivostok (1997) and 3 from Japan (1971) were used.
      PCR genotyping was performed by a set of marker genes of 7 pathogenicity islands
      (VPaI-1 - VPaI-7) and a number of other pathogenicity factors. RESULTS: All the
      strains isolated in 1970s differed significantly by sets of VPaI marker genes. In
      contrast to causative agents of outbreak in Vladivostok that contain all 7 VPaI
      genes (that is, members of the pandemic group that had spread globally since
      1996) none of the O4:K12 and O4:K8 Novorossiysk strains contained the full set of
      all the VPaI genes. However this set was distributed among the members of the
      group. CONCLUSION: Taking into account that O4:K12 and O4:K8 serogroups are
      considered by a number of authors as O3:K6 serovariants, PCR-screening data
      obtained by us allows to assume that horizontal transfer of mobile elements
      (VPaI) between strains circulating in the region could have led to the formation
      of pandemic clones already in the 1970s. This implies that in several coastal
      regions in certain periods of time conditions that favor these process may form,
      and risk of infection with pandemic clones is associated not only with import of
      seafood.

PMID- 23163033
TI  - [Analysis of outbreak of anthrax in Omsk region in 2010].
AB  - AIM: Carrying out analysis of epizootologic-epidemiologic situation on anthrax
      that had emerged in Omsk region in 2010 when horse meat from epizootic focus of
      anthrax was used in production of meat semi-finished products. MATERIALS AND
      METHODS: Study of samples for detection of anthrax causative agents and strain
      identification was performed according to guidelines 1.3.2569-09. Strain
      genotyping was performed by MLVA method. RESULTS: The epizootologic-epidemiologic
      investigation performed allowed to detect the causes of emergence of anthrax
      outbreak, its routes and factors of transmission. MLVA genotyping results gave
      evidence on the single origin of Bacillus anthracis strains isolated from sick
      animals, humans and food substances. CONCLUSION: Timely execution of a complex of
      epizootic and epidemic control measures allowed to localize epizootic and
      epidemic focus of anthrax as well as prevent a possible large scale development
      of epidemic complications.

PMID- 23163035
TI  - [Evaluation of the effect of mass vaccination against hepatitis B in the Russian
      Federation].
AB  - AIM: Evaluate the effect of mass vaccination against hepatitis B implemented
      within the framework of national project Health on the rate of development of
      unfavorable outcomes of infection and on average lifetime of the population of
      Russia. MATERIALS AND METHODS: Hepatitis B markers (HBsAg, anti-HBc, HBeAg, anti
      HBe) were determined by enzyme immunoassayin 6211 blood serum samples from
      conditionally healthy population of 6 regions of the Russian Federation. Analysis
      of damage to health of the population caused by hepatitis B and favorable effect
      of mass vaccination against hepatitis B was performed by using mathematical model
      by Goldstein S.T. et al. (2005), that used results of detection of hepatitis B
      markers in discrete groups (women of childbearing age, children up to 5 years of
      age, adults aged 30 years and older). A formula developed by us was used to
      evaluate the effect of vaccination on the average lifespan of the population of
      the Russian Federation. RESULTS: The rate of HBsAg detection in the conditionally
      healthy population of the Tuva Republic was significantly higher (8.1%) than in
      other studied regions of the Russian Federation (p < 0.05): in Moscow Region-
      1.6%, in Rostov Region--1.6%, in Sverdlovsk Region--1.2%, Khabarosvk Region-
      2.0%, in Sakha (Yakutia) Republic--2.5%. The rate of detection of anti-HBc was
      significantly higher in the Tuva Republic and Sakha (Yakutia) Republic (46.2% and
      42.3%, respectively); in other regions: Moscow Region--13.6%, Rostov Region-
      18.9%, Sverdlovsk Region--17.5%, Khabarovsk Region--21.0%. HBeAg in women of
      childbearing age was detected only in the Tuva Republic (0.4%). The mathematical
      analysis performed demonstrated that the level of coverage of vaccination of
      newborn children that in the studied regions is 96.1-99.6% may lead to the
      reduction of morbidity and mortality from hepatitis B and its outcomes by 91-95%
      that exceeds the similar parameter obtained by using our model, described in the
      literature for Africa, Asia and Europe. The calculated level of decrease of
      morbidity and mortality from hepatitis B and its outcomes may lead to the
      increase of average lifespan of the population of the Russian Federation by 1.44 
      4.08 months. CONCLUSION: The strategy of vaccination of newborn children against
      hepatitis B employed in the Russian Federation significantly reduces the risk of
      this disease and development of unfavorable outcomes of the disease especially in
      hyper endemic regions and promotes the increase of average lifespan of the
      population of Russia.

PMID- 23163034
TI  - [Study of cross-activity of Streptococcus pneumoniae antigen preparations].
AB  - AIM: Study cross-activity of S. pneumoniae antigen preparations. MATERIALS AND
      METHODS: Antigen preparations were obtained by ultrasound disintegration (from
      bacteria in R-form), extraction with water (from serotype 3 bacteria), cetavlon
      and trichloroacetic acid (from serotype 6A bacteria). Chemical composition and
      immunochemic properties of preparations were studied by contemporary methods as
      well as in experiments with direct and cross-protection of mice from infection.
      RESULTS: 3 of 4 preparations (except ultrasound disintegrate) had approximately
      30% of protein. In immunodiffusion reaction they interacted with hyper immune
      rabbit sera obtained against 12 various pneumococcus serotypes--1, 3, 4, 6A, 6B,
      9V, 9N, 14, 18C, 19A, 19F and 23F. In animal experiments 30 - 70% of mice were
      protected from subsequent infection with knowingly high dose of homologous and 3
      heterologous pneumococcus strains. In immunoblotting the highest number of
      components serologically active with heterologous sera was formed by cetavlon
      extract (12 - 23). Addition of capsule polysaccharides to the preparation
      increased its cross-protective activity. CONCLUSION: By data set and the highest
      yield, water extract is reasonable for isolation of cross-reactive proteins of
      pneumococcus. Development of another method of extraction from cultural fluid is
      necessary for obtaining extracellular protein antigens. Generation of vaccines
      containing cross-reactive proteins of pneumococcus and capsule polysaccharides is
      a promising direction.

PMID- 23163036
TI  - [Immunity to polioviruses in children population of various territories of the
      Russian Federation].
AB  - AIM: Analyze the state of population immunity to polioviruses in children
      population of 14 administrative territories of the Russian Federation. MATERIALS
      AND METHODS: Antibody titers against reference vaccine poliovirus serotypes 1, 2
      and 3 were determined by using neutralization reaction in cell culture Hep-2.
      RESULTS: Several years after the termination of conduction of National
      immunizations days the percent of seronegative children was shown to increase,
      especially to poliovirus serotype 3, in most of the territories. Possible reasons
      for fluctuation of geometric mean antibody titers against polioviruses in
      children in various territories as well as in various years in the same territory
      were established. CONCLUSION: Quality vaccine prophylaxis and control of
      population immunity state among children population play an important role in the
      maintenance of Russian Federation status as a country is free from poliomyelitis.

PMID- 23163037
TI  - [Technological approaches to development of whole-virion inactivated vaccine from
      recombinant strain against A/H5N1 influenza in the Republic of Kazakhstan].
AB  - AIM: Development of technological stages of preparation of experimental influenza
      whole-virion inactivated adsorbed vaccine based on recombinant influenza virus
      strains NIBRG-14 and A/Astana/RG/6:2/2009. MATERIALS AND METHODS: 2 recombinant
      vaccines influenza strains were used in the study--NIBRG-14 and
      A/Astana/RG/6:2/2009. Purification of native virus-containing allantoic fluid was
      performed by ion-exchange chromatography. The virus was inactivated by
      formaldehyde. Merthiolate at concentration of 0.1 mg/ml was added to the vaccine
      as a preserving substance. Aluminium hydroxide was used as an adjuvant.
      Harmlessness and immunogenicity (HI) of the constructed preparation are
      determining. RESULTS: Virus-containing materials from recombinant strains with
      biological activity of 8.5 - 9.0 lg EID50/cm3 and hemagglutination activity of
      1:256 - 1:1024 in chicken embryos were obtained. Optimal inactivation regimen of
      non-purified suspensions by formaldehyde was established and combined scheme of
      purification and concentration of influenza virus was selected that provide
      harmlessness and immunogenicity of experimental samples of inactivated vaccines
      against highly pathogenic influenza A/H5N1 in experiments in mice. CONCLUSION:
      The data obtained on quality parameters of intermediate products and final
      vaccine give evidence on their compliance with normative parameters for whole
      virion influenza purified vaccine.

PMID- 23163038
TI  - [Immunocorrection of apoptogenic effect of pertussis preparations with
      neutrophilokines].
AB  - AIM: Study the possibility of resistance increase of macrophages of experimental
      animals to apoptogenic effect of pertussis preparations with neutrophilokines.
      MATERIALS AND METHODS: Apoptosis was evaluated in Coulter flow cytofluorimeter
      after staining with propidium iodide, as well as by characteristic morphologic
      changes in cells stained by histological preparations and by DNA fragmentation.
      RESULTS: The studies performed showed that pertussis preparations cause apoptosis
      of peritoneal macrophages leading to their alteration. Neutrophilokines induced
      by pertussis preparations were also established to suppress macrophage apoptosis.
      CONCLUSION: The results of our studies indicate the possibility to use
      neutrophilokines for immunocorrection of macrophage apoptosis induced by
      pertussis preparations.

PMID- 23163039
TI  - [Macrophage apoptosis as a mechanism of pathogenic effect of diphtheria
      infectious agent].
AB  - AIM: Study of the apoptogenic effect of Corynebacterium diphtheriae toxigenic
      strains on mice peritoneal macrophages in vitro. MATERIALS AND METHODS:
      Evaluation ofapoptosis induced by Corynebacterium diphtheriae, Corynebacterium
      pseudodiphtheriticum, Staphylococcus aureus, Streptococcus pyogenes strains was
      performed by characteristic morphological changes in macrophages in smears
      stained by azure eosin by Romanovsky-Giemsa. RESULTS: Apoptogenic activity of
      diphtheria infectious agent was established to be determined by diphtheria
      exotoxin at early (after 1 hour) and surface structures and pathogenicity enzymes
      at later (3 hours) stages of effect. CONCLUSION: The ability of diphtheria
      infectious agent to cause macrophage apoptosis is one of the mechanisms of
      realization of its pathogenic properties determined by the effect of diphtheria
      exotoxin, as well as its surface structures and pathogenicity enzymes. The
      increase of apoptogenic activity of toxigenic strains of C. diphtheriae in
      association with S. pyogenes may be a pathogenetic base of formation of prolonged
      forms of bacteria carriage against the background of chronic ENT pathology.

PMID- 23163040
TI  - [Prebiotic properties of mannose and its effect on specific resistance].
AB  - AIM: Study prebiotic properties of mannose and its effect on colonization
      resistance in experiments in mice. MATERIALS AND METHODS: Experimental dysbiosis
      was induced by introduction into non-linear mice of doxycycline hydrochloride.
      Prebiotic properties of mannose were studied by a single per oral administration
      to mice of increasing doses of preparation for a week compared with probiotics
      lactobacterin and bifidumbacterin. Lumen microflora was analyzed in feces. TNF
      alpha level was determined by using a commercial kit OpTEIA ELISA Kit. Phagocytic
      activity of neutrophils and macrophages was studied in a cytochemical test of
      nitroblue tetrazolium reduction (NTT test) and by luminol-dependent
      chemiluminescence. Phagocytic activity and digestive ability of alveolar
      macrophages was studied. RESULTS: The ability of mannose along with probiotic
      preparations bifidumbacterin and lactobacterin to restore the composition and
      numbers of indigenous microflora of mice under the conditions of experimental
      dysbiosis was revealed. Per oral administration of mannose and probiotic strains
      together with mannose was established to cause stimulating effect on functional
      activity of macrophages increasing ingesting and digesting ability of the cells
      and facilitates reduction of TNF-alpha levels. CONCLUSION: Mannose has prebiotic
      effect; the ability of mannose to induce expression of pro- and anti-inflammatory
      cytokines gives evidence of immunostimulating properties of the monosaccharide.

PMID- 23163041
TI  - [Suppression of viability of staphylococci cells by 1270 nm laser beam].
AB  - AIM: Study the effect of 1270 nm wavelength laser exposure on the viability of
      Staphylococcus aureus and S. epidermidis cells in vitro. MATERIALS AND METHODS:
      Reference strain S. aureus 209P and clinical isolate S. epidermidis 26/193 that
      form bacterial biofilm were used in the study. Ica gene presence in S.
      epidermidis 26/193 that controls biofilm formation was confirmed in the study by
      PCR with a primer that generates a specific 814 n.p. amplicon. Experimental
      device by "New surgical technologies, Ltd." was used as a source of emission. The
      device has a continuous emission mode of laser semiconductor diodes with 1270 nm
      wavelength. Maximum regulated power of the emission is up to 3 W. Emission power
      in the studies performed was 150 mW. The time of exposition was 5, 10, 15 and 30
      minutes. The amount of viable cells in the experiment and control was determined
      by calculating CFU/ml. Evaluation of bacterial biofilm formation was performed by
      the method described in O'Toole G.A. et al. (2000). RESULTS: A decrease of the
      number of viable forms of S. aureus 209P by a mean of 52 +/- 6.0% and 76 +/-
      4.0%, and of S. epidermidis 26/193 by a mean of 48 +/- 4% and 64 +/- 5% for 15
      and 30 min exposition, respectively, and a significant suppression of biofilm
      formation by staphylococci was shown. CONCLUSION: Exposure to 1270 nm laser
      renders a moderate bactericidal effect on staphylococci cells and significantly
      suppresses their bacterial biofilm formation.

PMID- 23163043
TI  - [Low-manifest infections in children and adolescents with consequences of
      perinatal damage of nervous system].
AB  - AIM: Study the specter of low-manifest infections (LMI) and their role in
      children and adolescents with diseases of central nervous system (CNS) against
      the background of consequences of perinatal damage of nervous system (PDNS).
      MATERIALS AND METHODS: Infectologic and neurologic examinations were carried out
      in 42 patients with consequences of PDNS (17 girls and 25 boys, 3 - 15 years).
      Detection of LMI resulted in etiotropic therapy with evaluation of clinical and
      laboratory data in dynamics. RESULTS: In 93% (39/42) of patients causative agents
      of LMI were diagnosed in various combinations and in various biological
      materials. Among those: Chlamydia spp.--in 71% of patients, Mycoplasma spp.--in
      31%, Ureaplasma urealyticum--in 14% (in total the listed microorganisms were
      diagnosed in 83% of patients); Herpesviridae family viruses--in 75% (HHV-6--in
      67%, VEB--in 36%, CMV--in 11%, HSV-1,2--in 11%). Combination of Chlamydia spp.
      with HHV-6 (R tetr = +0.61) and with VEB (R tet = +0.74) (P < 0.05) was detected.
      None of the patients had typical signs of encephalitis clinically or based on
      MRT. MRT signs of gliosis-atrophic changes in the CNS were detected in all the
      patients. Reduction of a number of psycho-neurologic and neurologic syndromes was
      noted in all the patients during LMI therapy. CONCLUSION: Most of the patients
      with consequences of PDNS had low-intensity inflammatory-degenerative process in
      the CNS determined by LMI, first of all by Chlamydia spp. as well as Mycoplasma
      spp.

PMID- 23163042
TI  - [Isolation of Shewanella algae from pleural exudate of patient with pneumonia].
AB  - AIM: Clinical-microbiological description of the first case in Russia of
      isolation of S. algae bacteria from clinical material. MATERIALS AND METHODS:
      Patient P., 23 years of age, diagnosis: right-sided distal pneumonia, severe
      course; parapneumonic empyema of pleura. Bacteria isolation, cultural and
      biochemical tests differentiating S. algae and Shewanella putrefaciens were
      performed according to Holt H.M. et al., 2005. Identification of bacteria, tests
      of sensitivity to antibiotics were carried out by automatic system Vitek 2
      (bioMerieux) and additionally by disc-diffusion method. RESULTS: S. algae in
      association with Serratia marcescens were isolated from pleural exudate of the
      patient with pneumonia. S. algae bacteria had typical taxonomical features and
      pathogenicity factors (lipase, gelatinase, beta-hemolysin); were resistant to
      benzylpenicillin, amoxicillin, cefazolin and sensitive to other beta-lactam
      antibiotics, aminoglycosides, fluoroquinolones, macrolides, tetracycline.
      CONCLUSION: S. algae bacteria isolated from pleural exudate of the patient with
      pneumonia are etiologically significant in parapneumonic empyema of pleura.

PMID- 23163044
TI  - [Antiviral activity of polyprenylphosphates in experimental infection caused by
      hepatitis C virus in vitro].
AB  - AIM: Study antiviral effect of sodium polyprenylphosphate (PPP) in experimental
      infection model caused by hepatitis C virus (HCV) in cell culture. MATERIALS AND
      METHODS: Cytopathogenic variant of HCV isolated from blood serum of a chronically
      infected patient was used. HCV infectious dose was 10.0 TCD50. Highly sensitive
      to cytopathogenic effect of HCV continuous swine embryo kidney cells (SPEV) as 1
      day monolayer grown in 24 well plastic plates on 199 medium with 10% calf serum
      with addition of L-glutamine and antibiotics (100 U/ml) were used. PPP was used
      in concentrations that do not have cytotoxic effect (from 60 to 7.5 microg in 50
      microl); introduced into SPEV cell cultures immediately after infection, 24 hours
      before or 24 hours after the infection of cells with HCV. Infectious activity of
      HCV was evaluated by using Reed-Muench formula based on results of medium samples
      titration obtained 3 days after the infection of cells. RESULTS: PPP was shown to
      have antiviral properties when added into the cell cultures immediately after the
      infection with HCV. Under the effect of PPP HCV titers were established to
      decrease by 3.0 lg (PPV dose of 60 microg) and by 1.9 lg (PPV dose of 30 microg).
      Positive effect was also obtained for prophylactic use of PPP. When PPP at a dose
      of 60 microg was introduced 24 hours before the infection of SPEV with HCV, the
      titer of the virus decreased by 3.5 lg. Prophylactic administration of low doses
      of the preparation (7.5 and 15.0 microg) also showed evident antiviral effect
      (decrease of infectious activity of HCV by 3.2 - 2.3 lg, respectively).
      CONCLUSION: PPP at the doses tested has an ability to reduce concentration of HCV
      in SPEV cell cultures when added immediately after infection or 24 hours before.

PMID- 23163045
TI  - [Intestine dysbiosis and atopic dermatitis in young children].
AB  - AIM: Study the intensity of anti-endotoxin response in intestine of children with
      atopical dermatitis and intestine dysbioses. MATERIALS AND METHODS: 110 children
      with atopic dermatitis of various localization were examined in an outpatient
      setting. Besides detection of dysbiotic disorders in intestine by using
      bacteriological seeding on differential-diagnostic media and criteria of
      evaluation of degree of micro-ecological disorders according to Industry standard
      of Ministry of Health of Russian Federation "Protocol of patient management.
      Intestine dysbacteriosis" (2003), content of antibodies against LPS of
      enterobacteria belonging to various immunoglobulin classes (IgG, IgA, IgM, IgE)
      by EIA was studied in coprofiltrates. RESULTS: An increase of content of various
      immunoglobulins, specific LPS of enterobacteria that depended on the degree of
      intensity of dysbiotic disorders was detected in children. Allergization in
      children correlated with an increase of level of anti-endotoxin IgE and IgM (0.8
      +/- 0.2) and decrease of IgA content in intestine (-0.8 +/- 0.2). The higher the
      level of serum anti-LPS antibodies, the more frequently allergic manifestation
      occur in children. CONCLUSION: Correlation between the level of anti-endotoxin
      serum IgE and frequency of occurrence of allergic manifestations in children was
      shown.

PMID- 23163047
TI  - [Rift valley fever].
AB  - In the last quarter of century virus of Rift valley fever (RVF) sharply extended
      its distribution by moving from Africa to Asia and evolving from low- to high
      pathogenic for humans causing severe hemorrhagic disease, practically equaling in
      this respect with some members ofa group of extremely dangerous pathogens.
      Morbidity and epidemics of RVF are analyzed. Evolution of epidemic development of
      the infection is examined. Necessity of development of means and methods for
      diagnostics, prophylaxis and therapy of RVF is underlined.

PMID- 23163046
TI  - [Mechanisms of resistance of enterococci to antimicrobial proteins and peptides].
AB  - Mechanisms of resistance of bacteria genus Enterococcus to the most important
      factors of innate immunity of the host--antimicrobial proteins and peptides--are
      described in the review. Data on enterococci lysozyme resistance associated with
      modification of peptidoglycan and changes in the net charge of the bacterial cell
      surface are presented. The role of enterococci sigma-factor with extra
      cytoplasmic SigV function is described. Evidence on microbial
      activation/degradation of neutrophil alpha-defensin (HNP-1), antibacterial
      peptide LL-37, cecropin, beta-lysine (thrombocytic cationic peptide) is
      presented. The accumulated experimental material is discussed from the position
      of persistence of enterococci--both pathogens causing various infectious
      processes and commensals composing a part of normal host microflora.

PMID- 23163048
TI  - [Role of infectious agents in the emergence of malignant tumors].
AB  - According to the data of the International Agency for Research on Cancer (IARC),
      at least 6 virus species (HPV, EBV, HHV-8/KSHV, HTLV-1, HBV, HCV), 4 helminthes
      species (Schistosoma haematobium and japonicum, Opisthorchis viverrini,
      Clonorchis sinensis) and I bacterium species (Helicobacter pylori) have been
      proved to be capable of causing the development of cancer. The analysis of the
      data available shows that Merkel cell polyomavirus (MCV), herpes simplex virus
      (HSV), John Cunningham polyomavirus (JCV), monkey virus 40 (SV40),
      cytomegalovirus (CMV), xenotropic murine leukemia virus (XMRV), Helicobacter
      bilis and hepaticus, Campylobacter jejuni, Fusobacterium varium, enteropathogenic
      Escherichia coli, enterotoxigenic Bacteroides fragilis, Bacteroides vulgatus,
      Prevotella spp., Streptococcus bovis and anginosus, Treponema denticola,
      Salmonella typhi, paratyphi and typhimurium, Borrelia burgdorferi, Bartonella
      spp., Mycobacterium tuberculosis, Chlamydia pneumoniae, trachomatis and psittaci,
      Neisseria gonorrhoeae, Propionibacterium acnes, Tropheryma whippelii, Schistosoma
      mansoni, Opistorchis felineus, Strongyloides stercoralis, Taenia solium, Candida
      spp., Paracoccidioides brasiliensis, Histoplasma capsulatum and Trichomonas
      vaginalis can also be potential etiological agents of cancer. Apparently,
      detection of new associations between infectious agents and risk of the
      development of cancer will facilitate progress in elaboration of prophylaxis
      measures, early diagnostic methods and, probably, methods of treatment of
      malignant tumors.

PMID- 23163050
TI  - Running out of patience. Continuing problems with errors spur group to launch
      $500 million safety initiative.
AB  - A half-billion-dollar initiative to battle preventable error would team engineers
      and other professionals with clinicians to create highly reliable systems. That
      will give physicians and nurses more time to talk to patients and their families
      about their concerns and questions. "Every; patient needs to be listened to,"
      says James Guest, left, of Consumers Union.

PMID- 23163049
TI  - [Reservation forms of plague infectious agent in Tuva natural focus].
AB  - Data characterizing the reservation forms of plague infectious agent in Tuva
      natural focus are presented in the review. Yersinia pestis was shown to persist
      most of the year in Citellophilus tesquorum altaicus imago --the main carrier,
      getting into the animal organism only for a short time. An increased ability to
      aggregate in autumn and accumulate in clumps of C. tesquorum altaicus females
      that are more adapted to survive the cold season compared with males promote the
      persistence of the microorganism. The plague infectious agent in the altered form
      survives in the organism of females not only the winter period but also longer
      periods of time that is demonstrated by the facts of detection of it after 646
      days of staying in the carrier. Moreover Yersinia pestis can persist for more
      than 400 days in the substrate of the nest of long-tailed ground squirrel
      infected by excrements and corpses of plague fleas. The substrate of the nest
      infected in summer-autumn period of the previous year may determine the primary
      infection of ground squirrels by plague infectious agent in the next epizootic
      season. On ground squirrels infected during contact with nest substrate,
      infection of intact fleas may be possible, and so the initiation of a new cycle
      of transmission of the infectious agent. Adaptation of the plague infectious
      agent to unfavorable existence conditions in the carrier is expressed in the
      changes of its morphology and ultrastructure that is evidenced by the facts of
      isolation of the infectious agent from corpses of fleas situated in the
      substrate, in the L-form, as well as results of phase-contrast and electron
      microscopy of the digestive tract of C. tesquorum altaicus.

PMID- 23163051
TI  - Big regs, big changes. Latest rules delay some deadlines, push encryption.

PMID- 23163052
TI  - Deal volume takes hit... but value of healthcare transactions climbs.

PMID- 23163053
TI  - Uncertainty: How will Braly's successor fix WellPoint's troubles?

PMID- 23163054
TI  - An authentic call for compromise? Christie's comments on bipartisanship sound
      more like empty promises.

PMID- 23163055
TI  - Expertise on call: Annual outsourcing report shows providers of all sizes
      continue to pursue arrangements that offer savings for their revenue-strapped
      operations.

PMID- 23163056
TI  - Healthcare on sale: Texas hospital lowers prices, raises level of debate.

PMID- 23163057
TI  - Uninsured rates fall. But reform critics cite bad economy as source.

PMID- 23163058
TI  - CUSP highs and lows. Program data positive, but participation uneven.

PMID- 23163059
TI  - A radioactive problem. Some shirk precautions against 'dirty bomb' threat.

PMID- 23163060
TI  - Target hot spots... not home health sector: group.

PMID- 23163061
TI  - Taking their medicine. More hospitals mandate flu shots for workers.

PMID- 23163062
TI  - ONC drops governance plan. But NwHIN security, privacy concerns remain.

PMID- 23163063
TI  - Regulation revamp. Governor proposes making Mich. Blues taxable.

PMID- 23163064
TI  - When down is looking up. Some gains in trends for the poor and uninsured, but no
      cause for celebration.

PMID- 23163065
TI  - Shades of green. Annual Design Award winners feature sustainability,
      functionality.

PMID- 23163066
TI  - XXL MOBs. Medical office buildings grow in girth.

PMID- 23163067
TI  - Dermatofibroma: a curious tumor.

PMID- 23163068
TI  - Cosmeceuticals.

PMID- 23163069
TI  - Therapeutic effects of minoxidil high extra combination therapy in patients with
      androgenetic alopecia.

PMID- 23163070
TI  - Aging and facial changes--documenting clinical signs, part 1: clinical changes of
      the aging face.
AB  - The process of aging induces the transformation of the face with changes that are
      usually classified as either chronological or photo induced and that affect the
      shape, the texture, and the color of the face. Facial shape is mainly transformed
      by the evolution of bones and soft tissues (muscles, fat, and skin) in addition
      to noticeable effects of gravity. Skin texture is mainly determined by wrinkles,
      which arise from atrophy of the skin layers, elastosis, and facial expressions.
      Skin color is related to the distribution of skin chromophores and the structure
      of the dermis, which affects light scattering. All facial changes are dependant
      on sex, ethnicity, and lifestyle. They affect self-perception and social
      interactions and can sometimes be slowed down or reversed using appropriate
      clinical procedures (e.g., dermatological, surgical, and cosmetic interventions).

PMID- 23163071
TI  - Footwear dermatitis: pathogenesis--part I.
AB  - Footwear dermatitis is an important aspect of contemporary dermatology. The
      causative factors are constantly changing just as the footwear industry is
      continually changing. These range from the leather itself to rubber accelerators
      and from dyes to even metal trim.

PMID- 23163072
TI  - On bossing: taking charge without the facts.

PMID- 23163073
TI  - Sorilux (calcipotriene) foam 0.005%.

PMID- 23163074
TI  - How dirty are the dirty dozen ingredients in cosmetics?

PMID- 23163075
TI  - Nail biopsy for melanonychia.

PMID- 23163076
TI  - Historical diagnosis & treatment. Syphilis primaria. 1910.

PMID- 23163077
TI  - Two contrasting post-zoster dermatomal phenomena.
AB  - A 29-year-old, normotensive, nondiabetic man presented with a 9-day history of a
      scaly, pruritic eruption involving the right chest, axilla, and arm. He had a
      history of herpes zoster involving the same areas about 4 weeks ago. The present
      eruption started after the herpetic lesions had healed. Examination revealed
      scaly, erythematous plaques and papules involving the right side of the chest,
      axilla, and arm in a dermatomal pattern (figure 1). Removal of the scales
      revealed underlying bleeding points (positive Auspitz sign). The rest of the
      body, including scalp, palms, soles, and nails, were normal. There was no history
      suggestive of psoriasis in any family member. Systemic examination and routine
      investigations were noncontributory. A clinical diagnosis of psoriasis was made
      and confirmed by histopathologic examination of a skin biopsy sample. The patient
      was prescribed a topical clobetasol cream and oral levocetirizine. The eruption
      resolved completely after 3 weeks. A 43-year-old normotensive, nondiabetic woman
      presented with a 2-day history of fever, arthalgias, and generalized erythematous
      dermatitis. Five days ago, the patient had a toothache for which she was
      prescribed injectable ampicillin. After receiving ampicillin for 3 days, she
      developed fever, myalgias, and arthalgias, which was followed several hours later
      by an erythematous eruption. The dermatitis started on the trunk and, over a
      period of several hours, progressed to involve the face and limbs. The eruption
      was slightly pruritic. History revealed herpes zoster 7 months ago involving left
      thoracic dermatomes, for which the patient was treated with valacyclovir (1 g
      thrice a day x 7 days) and analgesics. There was no history of post-zoster
      neuralgia. On examination, the patient was febrile (oral temperature 102 degrees
      F), her heart rate was 118 beats per minute, and her blood pressure was 110/70 mm
      Hg. Cutaneous examination revealed an erythematous, maculopapular dermatitis
      involving the face and limbs in a bilaterally symmetrical pattern; the palms and
      soles were also bilaterally involved. The whole of the trunk was involved with
      erythematous and, in places, violaceous, maculopapular eruption except for a
      small area on the left side corresponding to T8 and T9 thoracic dermatomes
      (Figure 2). Complete blood cell counts revealed eosinophilia (9%) and liver
      function tests, kidney function tests, random blood sugar, routine urine
      examination, and blood and urine cultures were noncontributory. Histopathologic
      examination of lesional skin biopsy revealed an intense mononuclear cell
      infiltration with many eosinophils and an interface dermatitis with hydropic
      degeneration of basal keratinocytes, while in the spared area, only slight
      lymphocytic infiltration was present in a perivascular distribution. Based on the
      history and examination, a diagnosis of ampicillin-induced drug dermatitis was
      made. The ampicillin was stopped and the patient was put on a short course of
      oral prednisolone, antipyretics, and topical calamine. The patient was afebrile
      in 2 days and the eruption resolved completely in 8 days.

PMID- 23163078
TI  - Cupping-related skin lesions.
AB  - In the outpatient department of the National Institute for Health, Migration and
      Poverty (NIHMP) in Rome, Italy, and at the Italian Dermatological Hospital in
      Mekele, Ethiopia, from January 1, 2007, to December 31, 2009, 47 patients,
      adults, and children showing typical circular skin lesions referable to cupping
      were observed. The patients (32 men and 15 women) underwent complete
      dermatological examination, and their case histories were collected with the aid
      of a cultural mediator from the same linguistic or cultural area of the patient.
      The clinical picture included blue-red, circular erythematous spots, sometimes
      covered with crusts, consistent with recent cupping (figure 1 and figure 2). In
      some cases, particularly in older lesions, atrophic-cicatricial lesions and
      irregular, normal-color, slate gray, or hypochromic skin surface were observed
      (figure 3). Lesions were observed on the back, on the presternal region (figure
      4), and, in case of pathologies causing abdominal swelling (i.e., kwashiorkor,
      intestinal parasitosis), on the abdomen (figure 5). The clinical pictures
      initially diagnosed as dermatophytoses or lesions caused by traumas or violence
      were later proved to be cupping-related outcomes or complications.

PMID- 23163079
TI  - Parotid tuberculosis associated with cutaneous tuberculosis on a medial
      epicanthus.
AB  - An 83-year-old woman presented with a 2-month history of a gradually enlarging,
      reddish, crusted papule on her left medial epicanthus. Her medical history did
      not reveal any systemic disease. She gave no personal history of tuberculosis or
      any systemic symptoms, such as night sweat, weight loss, and pulmonary
      abnormalities. Her husband had been treated for pulmonary tuberculosis 30 years
      ago. A dermatologic examination revealed a 2.5 x 1.2-cm nontender, erythematous
      plaque with fine, white adherent scales on the left medial epicanthus (figure
      1A). All laboratory values were within the normal range. Results from a
      tuberculin skin test were initially negative. A skin biopsy was performed, and a
      pathological examination demonstrated multiple noncaseating granulomas with
      various diameters in the reticular dermis and an infiltrate of neutrophils and
      lymphocytes in the surrounding dermis (figure 2). Periodic acid-Schiff, Ziehl
      Nilsen, gram, and giemsa stains were negative for any microorganism. Leishman
      Donovan-like bodies were observed within the epitheloid histiocytes that formed
      the granulomas. The pathological diagnosis was granulomatous dermatitis. The
      patient was diagnosed with cutaneous leishmaniasis (CL) based on her clinical
      appearance and histopathological findings, although the parasite was not detected
      in the tissue specimens. Treatment with intralesional glucantime for 5
      consecutive weeks did not improve her condition. By the end of the fifth week,
      the patient developed asymptomatic facial swelling and a 1.5 x 1.2-cm
      erythematous plaque in the left parotid area (figure 1B). An ultrasonographic
      examination demonstrated a 13 x 11 x 17-mm hypoechoic mass, which suggested
      pleomorphic adenoma. In addition, lymph nodes, the largest of which were 9 x 10
      mm, were noted in the left cervical area. A skin biopsy from the erythematous
      plaque of the left parotid area demonstrated diffuse neutrophilic infiltration
      with formation of focal granulomas. Tuberculosis was suspected, and mycobacterium
      tuberculosis (MT) was isolated from the culture. A tuberculin skin test was
      performed again, which was positive (12 mm). The erythrocyte sedimentation rate
      was 35 mm/h, and all other laboratory tests were within normal limits. Pulmonary
      radiography and thoracic computerized tomography findings were normal. Fine
      needle aspiration biopsy and ultrasonographic examination of the parotid mass
      were performed, which revealed necrotic material with neutrophils and lymphocytes
      (figure 3). We treated the patient with a standard antituberculous regimen,
      comprising isoniazid 300 mg/d, rifampin 600 mg/d, ethambutol 1200 mg/d, and
      pyrazinamide 1500 mg/d. By the end of the second month of treatment, the patient
      improved considerably. There was a marked reduction in facial swelling, and the
      lesion on the left medial epicanthus regressed dramatically (Figure 4A and Figure
      4B). No adverse effects of the medication occurred. An additional 7 months of
      therapy with isoniazid and rifampin was planned.

PMID- 23163080
TI  - Analysis of patient awareness and demographic studies in follicular unit
      extraction.

PMID- 23163081
TI  - More about "modesty and the skin".

PMID- 23163082
TI  - Taking the risk. Despite meningitis outbreak, some hospitals have little choice
      but to rely on compounding pharmacies.
AB  - In the wake of a deadly meningitis outbreak tied to a compounding pharmacy, many
      hospitals will still have to use such facilities because they have no alternative
      for hard-to-obtain drugs. "I don't think we would stop buying from compounding
      pharmacies, but it will cause people to strengthen evaluations of what they are
      buying," says Alison Apple, left, of Methodist Healthcare, Memphis, Tenn.

PMID- 23163083
TI  - Bipartisan effort. Dems, GOP call for investigation into outbreak.

PMID- 23163084
TI  - New ventures for Dignity. GPO, partnership aim to ease supply cost bite.

PMID- 23163085
TI  - Penalties don't show effect. Study: infection rates not altered by nonpayment.

PMID- 23163086
TI  - Prime's opportunity. Calif.-based chain is growing fast, but has to overcome
      'controversial' image.

PMID- 23163087
TI  - Blue Button gains fans, apps. Simple tech from VA puts interoperability to work.

PMID- 23163088
TI  - Reason for optimism. Best Places to Work recipients give healthcare industry much
      to strive for.

PMID- 23163089
TI  - Welcome ... your bill is ready. More hospitals informing patients of payment due,
      during and even before they begin their stay.

PMID- 23163090
TI  - Making behavioral health a primary concern. Providers taking an integrated,
      collaborative approach to treatment.

PMID- 23163091
TI  - Major merger. Catholic Health East, Trinity deal stands out as hospitals, systems
      react to changes in healthcare.
AB  - Among the increasing number of deals that are creating larger healthcare systems
      across the country, the Trinity Health and Catholic Health East merger stands out
      for its size and scope. "In the world we live in, because of reform, we know
      scale matters, and we do believe that the opportunity that we see translates to
      synergy," says Joseph Swedish, left, president and CEO of Trinity Health.

PMID- 23163092
TI  - WaI-Mart's surgical strike. Retailer banks on workers needing less-costly care.

PMID- 23163093
TI  - Partnering up. Walgreen offers strategy to avoid readmissions.

PMID- 23163094
TI  - Under scrutiny. More control of compounding pharmacies sought.

PMID- 23163095
TI  - Anemic prospects? Nashville marketplace scuttled, doubts hang over N.Y, Cleveland
      projects.

PMID- 23163096
TI  - Audits said to put hospitals on track. But some targets criticize auditors for
      lacking healthcare-billing expertise.

PMID- 23163097
TI  - Changes from both sides. Participatory medicine society aims to improve patient
      physician dynamic.

PMID- 23163098
TI  - RAC 'em up. Have hospital payment audits finally crossed the common-sense line?

PMID- 23163099
TI  - Getting back to basics. Manage the increasing complexity of medical practice from
      the inside.

PMID- 23163100
TI  - Primary care with a personal touch. Medical Homes Survey reveals diverse
      settings, but single goal: increase quality of care.

PMID- 23163101
TI  - The long reach of medicine. International telemedicine becoming a growing force
      for U.S. hospitals.

PMID- 23163102
TI  - Diagnostic pathways for exclusion and diagnosis of kidney diseases.
AB  - In 2006, the German Society for Clinical Chemistry and Laboratory Medicine
      together with the Society of Nephrology founded a working group with the aim to
      develop diagnostic pathways for the detection and differentiation of renal
      diseases. Based on existing recommendations, these pathways may be structured to
      be a basis for implementation into hospital and laboratory information systems.
      The present paper describes the contents of these pathways regarding glomerular
      filtration rate, hematuria, leukocyturia and proteinuria.

PMID- 23163103
TI  - Neuroserpin upregulates in the early period of sustained spinal cord compression.
AB  - BACKGROUND: Neuroserpin (NSP) is a neuroprotective factor in the situation of
      ischemia of a brain, such as stroke. However, it has never been reported in the
      spinal cord, which is part of the central nervous system (CNS). METHODS: The
      expression of NSP was detected using Western blotting and neuron apoptosis
      detected by TUNEL staining following spinal cord ischemia caused by sustained
      compression in rats. RESULTS: The results showed that NSP was upregulated in the
      injury area of spinal cord, accompanied with the activation of micorglia and
      tissue plasminogen activator (tPA), which suggested that NSP also plays a
      neuroprotective role in spinal cord compression since neuronal apoptosis appears
      when NSP returns to normal levels or even lower. CONCLUSIONS: NSP upregulates in
      early periods of sustained spinal cord compression.

PMID- 23163104
TI  - The comparison of multilineage differentiation of bone marrow and adipose-derived
      mesenchymal stem cells.
AB  - BACKGROUND: To compare the roles of adipose and bone marrow derived mesenchymal
      stem cells (AMSCs and BMSCs) in multiple differentiation capacity to provide a
      theoretical basis for stem cell transplantation. METHODS: We isolated bone marrow
      and adipose derived mesenchymal stem cells and compared their phenotype, cell
      doubling time, the secretion of factors, and the ability of multi
      differentiation. RESULTS: BMSCs and AMSCs were similar in cell phenotype and the
      differences existed only between the expression of CD106. The proliferation rate
      of AMSCs was faster than of BMSCs (doubling time 28h vs. 39h) and the capacity to
      suppress T cell proliferation and activation was weakened in AMSCs. In addition,
      both sources of cells were able to differentiate into bone, fat, and cartilage
      which proved their stem cell properties. CONCLUSIONS: Cell origin and abundance
      were decisive factors in stem cell applications and with the same premise as for
      AMSCs and BMSCs, adipose tissue is a more promising source of stem cells.

PMID- 23163105
TI  - Evaluation of rapid influenza virus tests in patients with influenza-like illness
      in Thailand.
AB  - BACKGROUND: The influenza virus is responsible for causing major respiratory
      tract symptoms. A fast, accurate diagnosis is essential for efficient treatment,
      especially in patients with complications. The Rapid Influenza Diagnostic Tests
      (RIDTs) for influenza detection have been developed to subtype the influenza
      virus. The re-evaluation of the rapid test is needed in terms of specificity,
      sensitivity, and accuracy. METHODS: From August 13, 2010 to September 22, 2011,
      1,076 nasal aspirates were obtained from patients, ages ranging from 15 days to
      98 years, with symptoms of influenza-like illness (ILI) and evaluated by 2 types
      of RIDTs, Standard Diagnosis (SD) and QuickVue (QV) Rapid tests followed by real
      time RT-PCR. The results from the rapid test diagnoses were compared to those
      from real-time RT-PCR. RESULTS: During 2010 and 2011, the estimated sensitivity
      of the SD rapid test for seasonal H3, human pandemic H1N1, and influenza B
      infection was 49.4%, specificity was 84.1%, positive predictive value was 47.6%,
      and negative predictive value was 85% while those of the QV rapid test were
      63.4%, 96.7%, 94.8%, and 80.3%, respectively. Infant patients (< or = 5 years)
      yielded less false negatives while adolescents and adults (older than 5 years)
      showed more false negatives 8.8% and 15.2%, respectively. Using rapid test
      diagnosis, H3N2 influenza virus was found with more false negative results
      (11.1%) than the other viruses (1.1 - 3.5%). The SD rapid test appeared to be
      more sensitive than the QV test during high season activity while the QV test was
      more sensitive during the period of low influenza virus activity. CONCLUSIONS:
      Due to persistent genetic drift of the influenza virus, the available RIDTs
      should be re-evaluated each year. During 2010 - 2011, the QV rapid test showed
      more reliable results than the SD rapid test. However, the false negative results
      of H3N2 influenza virus detection during its peak should be cause for concern.
      Some of the results, e.g. patients with complications, should be compared with
      real-time RT-PCR as the gold standard method for detecting influenza virus
      infection.

PMID- 23163106
TI  - Reducing preanalytical laboratory sample errors through educational and
      technological interventions.
AB  - BACKGROUND: A correct preanalytical phase procedure is critical to get an
      adequate sample and consequently to achieve the most reliable laboratory results,
      promoting patient safety. Continuous laboratory staff changes create the need to
      establish improvement strategies to reduce the error risk. The objective was to
      show how the numbers of preanalytical errors related to unsuitable samples in a
      hospital setting decrease following two improvement strategies related to new
      technology and educational actions and how their effects were measured by
      monitoring indicators. METHODS: Samples were drawn by the laboratory and other
      hospital departments' nurses without previous patient appointment, therefore,
      prior tube preparation was not available before the phlebotomy. Corrective
      measures for these activities were established: educational program for nurses
      and a system of custom labels, which correlate each laboratory test in the
      Laboratory Information System (LIS) with the corresponding tube. Three phases
      were defined based on the implementation dates of the improvement actions to be
      assessed. The set of indicators designed to monitor the improvement related to
      clotted, hemolyzed, insufficient, and uncollected samples. Data were collected
      and indicators calculated from the LIS using a data warehouse application.
      Patient satisfaction with respect to phlebotomy was also measured annually using
      a scoring survey. RESULTS: There was a reduction in all types of preanalytical
      sample errors related to the improvement strategies adopted. The indicators
      demonstrated that the unavailable, insufficient, and clotted samples decreased
      between two- and three-fold, whereas hemolysis errors benefited more from these
      improvement strategies. Patient satisfaction with the laboratory and phlebotomy
      procedures improved over the past several years as based on the annual
      satisfaction surveys. CONCLUSIONS: The educational program for nursing personnel
      is relevant and important as can be seen in the decrease of sample errors and the
      resulting quality improvement. The custom label system minimizes the potential
      oversight of forgetting to draw a tube, which happens frequently when operating
      without appointments, by printing the labels according to requested tests.
      Detection, identification, and monitoring of the error and implementing
      strategies to improve preanalytical quality reduces error numbers and thereby
      improves patient safety and health system outcomes.

PMID- 23163107
TI  - Prognostic prediction of BRAF(V600E) and its relationship with sodium iodide
      symporter in classic variant of papillary thyroid carcinomas.
AB  - BACKGROUND: The aim of this study was to evaluate the prognosis of the classic
      variant of papillary thyroid carcinomas with the BRAF(V600E) mutation and 131I
      treatment failure in those tumors due to lower functional sodium iodide symporter
      expression. METHODS: 109 papillary thyroid carcinomas were associated with
      clinicopathologic features. The BRAF(V600E) mutation was evaluated by direct
      sequencing and sodium iodide symporter protein was determined by
      immunohistochemistry. RESULTS: We found that the BRAF(V600E) mutation was
      significantly associated with the classic variant of papillary thyroid carcinomas
      and was independent of tumor size, the presence of extrathyroid invasion and
      lymph node metastasis, advanced TMN stages, and a high risk of disease
      recurrence. Moreover, the BRAF(V600E) mutation was associated with a
      statistically significant lower functional NIS protein expression in the classic
      variant of papillary thyroid carcinomas. However, those statistically significant
      relationships were not found in the follicular variant of papillary thyroid
      carcinomas. CONCLUSIONS: The BRAF(V600E) mutation might be associated with a more
      aggressive phenotype and a poor prognosis, causing less NIS-mediated 131I uptake
      due to a lower functional NIS protein expression in the classic variant of
      papillary thyroid carcinomas. Our current study appears to be valuable for
      predicting prognosis and is of important clinical significance for surgery and
      131I treatment in patients with the classic variant of papillary thyroid
      carcinomas.

PMID- 23163108
TI  - Differentiation of Candida dubliniensis from Candida albicans by means of MALDI
      TOF mass spectrometry.
AB  - BACKGROUND: Species specific differentiation of the two closely related yeasts,
      Candida albicans and C. dubliniensis, is difficult in routine diagnosis. METHODS
      AND RESULTS: Here we show that MALDI-TOF MS is a practical and useful tool for
      the discrimination of C. albicans and C. dubliniensis, demonstrated by the
      analysis of reference strains from type culture collections and other well
      characterized isolates. The spectra of C. albicans and C. dubliniensis further
      revealed that each species consists of several clades. CONCLUSIONS: Reliable,
      routinely applicable methods for species specific differentiation of C. albicans
      and C. dubliniensis appear to be of particular importance to better understand
      the epidemiology and virulence of C. dubliniensis.

PMID- 23163109
TI  - First live birth in germany after re-transplantation of cryopreserved ovarian
      tissue: original device for initiation of ice formation.
AB  - BACKGROUND: The problem of post-cancer infertility is of significant concern. The
      cryopreservation of ovarian tissue before cancer therapy with retransplantation
      after convalescence is the key to solving this problem. METHODS: Cryopreservation
      of ovarian tissue was performed in 2005 after surgical operation, post-operative
      low-temperature 22 hour transportation, and freezing using a special, original
      design block constructed for the initiation of ice formation (ice-seeding). We
      present the construction and function of this block. RESULTS: In 2011, it was
      noted that a baby was born after thawing and re-transplantation of ovarian
      tissue. The technical and biological aspects of initiated crystals formation in
      the process of cryopreservation are emphasised and discussed. CONCLUSIONS: The
      first live birth in Germany after re-transplantation of cryopreserved ovarian
      tissue was noted. This cryopreservation was performed using the protocol
      described here. Block for auto-seeding of principally new construction
      recommended.

PMID- 23163110
TI  - Analysis of cardiac and renal endothelin receptors by in situ hybridization in
      mice.
AB  - BACKGROUND: Endothelin-1 (ET-1) is a multifunctional peptide, which is implicated
      in the renal and cardiac physicology as well as in many pathologies of these
      systems. ET-1's actions take place after the activation of two receptors: ET(A)
      and ET(B). The expression of these receptors may be modulated during the
      pathologic process. The analysis of the distribution and level of expression of
      the receptors in animal models is therefore crucial. METHODS: We developed a
      protocol for non-radioactive in situ hybridization for the mRNA of the two
      endothelin receptors on paraffin-embedded tissue using digoxigenin-labeled RNA
      probes. RESULTS: In heart and kidney, the staining was reliable and specific. In
      a mouse model for endothelin/nitric oxide imbalance, cardiac ET(B) expression was
      reduced. The distribution of the receptors was in accordance with the actual
      knowledge. Differences in cell specific expression are discussed. CONCLUSIONS: We
      developed a protocol for the in situ hybridization of the endothelin receptors in
      mice. Given that the endothelin system is implicated in the development of many
      diseases, we believe that this protocol may be useful for a number of future
      preclinical studies..

PMID- 23163111
TI  - Fast bedside measurement of blood count and C-reactive protein in newborns
      compared with conventional methods.
AB  - BACKGROUND: Abnormal complete blood count (CBC) and high plasma C-reactive
      protein (CRP) are associated with neonatal infections and could be helpful in the
      diagnosis of neonatal sepsis and to monitor the antibiotic treatment. OBJECTIVES:
      The aim of this work is to evaluate and compare the performance of a bedside
      analyzer for blood count and C-reactive protein (CRP) with a conventional
      analyzer in a neonatal population. METHODS: 150 capillary or venous blood samples
      of term and preterm newborns were processed on an ABX-MicrosCRP200 analyzer and
      on a SysmexXE2100 (conventional hematology analyzer) for CBC, leukocyte
      differential, reticulocytes, and nucleated red blood cells (NRBC); high
      sensitivity CRP (hs-CRP) was performed on a ModularPE. The differences between
      complete blood count and CRP were regressed against their means and assessed by
      means of intra-class-correlation. RESULTS: The intra-class-correlation for white
      blood cell (WBC) was 0.98, for hemoglobin 0.97, for hematocrit 0.96, for mean
      corpuscular volume 0.95, and for platelet 0.98. ABX-MicrosCRP200 overestimated
      the WBC (+1.27 x 10(3)/microL; p < 0.001), hematocrit (+1.80%; p < 0.001), and
      platelet (+13.55 x 10(3)/microL; p < 0.001). The intra-class-correlation for CRP
      was high (0.97), without systematic difference between the two values (p = 0.64).
      CONCLUSIONS: The agreement between the two methods was high for both tests.
      However, the SD of the difference for WBC and platelet could be clinically
      important in leukopenic or thrombocytopenic newborns.

PMID- 23163112
TI  - Development and validation of a rapid and reliable method for TPMT genotyping
      using real-time PCR.
AB  - BACKGROUND: It is widely accepted that many medications exhibit inter-individual
      variability in their efficacy and toxicity due to polymorphisms in genes encoding
      drug-metabolising enzymes. One of the most often cited examples in this context
      is thiopurine S-methyltransferase (TPMT) polymorphism. TPMT is a phase 2
      detoxification enzyme that catalyzes the S-methylation of thiopurine drugs such
      as thioguanine and 6-mercaptopurine. Approximately 11% of the Caucasian
      population carry a heterozygous deficiency of this enzyme causing intermediate
      enzyme activity, whereas 0.3% show a homozygous deficiency. In both cases, severe
      myelosuppression can develop upon treatment with thiopurines. These are commonly
      used in the treatment of leukemia. Therefore, genotyping of patients before
      treatment is absolutely necessary. Development of a fast and reliable real-time
      PCR application for TPMT genotyping would greatly improve thiopurine treatment
      regimens and allow the avoidance of adverse drug reactions. METHODS: Blood was
      obtained from a Caucasian cohort of 143 individuals. After extraction of DNA, all
      samples were genotyped for TPMT polymorphisms *2, *3A, *3B, and *3C by real-time
      PCR as well as by PCR-RFLP as the reference method, in order to validate the new
      method. RESULTS: Four different genotypes were found in the population studied.
      Of the 143 individuals investigated, 1 was heterozygous for TPMT*2 (0.70%), 2
      were heterozygous for TPMT*3B (1.40%), and 8 heterozygous for TPMT-*3C (5.60%).
      No homozygous genotype could be identified. In total, 7.7% of the individuals
      carried mutations. Results from the newly developed real-time PCR were 100%
      concordant with those obtained using standard PCR-RFLP analysis, leading to 100%
      sensitivity and specificity. The hands-on time is approximately one third of the
      time needed for standard PCR-RFLP methods. CONCLUSIONS: A new high-throughput
      genotyping method could be successfully established and optimised for the
      commonly found mutant alleles TPMT*2 (G238C), TPMT*3A (G460A and A719G), TPMT*3B
      (G460A), and TPMT*3C (A719G) via real-time PCR on the LightCycler (Roche)
      instrument and using the standard PCR-RFLP as reference method.

PMID- 23163113
TI  - Plasma malondialdehyde levels and risk factors for the development of chronic
      complications in type 2 diabetic patients on insulin therapy.
AB  - BACKGROUND: We assessed plasma malondialdehyde (MDA) levels as a biomarker of
      lipid peroxidation in type 2 diabetic patients on insulin therapy. Associations
      among MDA levels and some risk factors for the development of chronic
      complications of diabetes were also evaluated. METHODS: MDA, fasting glucose,
      fructosamine, urinary albumin, total cholesterol, HDL cholesterol, LDL
      cholesterol, triglycerides, creatinine, uric acid, serum albumin, lactate, high
      sensitive C reactive protein (hsCRP), and vitamin E were measured in 53 type 2
      diabetic patients and 26 healthy subjects. RESULTS: MDA levels were higher in
      type 2 diabetes insulin users (12.8 +/- 3.0 micromol/L) and type 2 diabetes no
      insulin users (10.3 +/- 2.1 micromol/L) compared to control subjects (8.2 +/- 2.1
      micromol/L). Fasting glucose, fructosamine, urinary albumin, and hsCRP were
      higher in all type 2 diabetic patients compared to controls. Significant
      correlations were observed between MDA and fasting glucose (r = 0.685, p <
      0.001), fructosamine (r = 0.526, p < 0.001), urinary albumin (r = 0.516, p <
      0.001), and the duration of type 2 diabetes (r = 0.401, p = 0.005). CONCLUSIONS:
      MDA levels increased in type 2 diabetes, especially in patients on insulin
      therapy. Chronic hyperglycemia and other biomarkers, such as urinary albumin,
      were correlated with MDA levels, suggesting the involvement of lipid peroxidation
      in the pathogenesis of diabetes complications.

PMID- 23163114
TI  - Development of microscopic review criteria by comparison urine flow cytometer,
      strip and manual microscopic examination.
AB  - BACKGROUND: Microscopic examination is essential for urine analysis, but a time
      consuming procedure. This study was undertaken to evaluate an automated
      urinalysis system - the Sysmex UF-1000i (URISYS 2400) for the analysis of urine
      constituents including chemistry components and particles. The objective was to
      screen urine samples and determine the screening criteria which would minimize
      the number of specimens reviewed with the microscope yet ensuring correct
      results. METHODS: A total of 1300 urine samples were sent for urinalysis using
      the automated system and compared with results obtained from manual microscopy
      using the Fuchs-Rosenthal counting chamber. RESULTS: Using Pearson statistics, we
      observed correlation between the UF-1000i and manual microscopy: for red blood
      cells (RBCs) r was 0.949, for white blood cells (WBCs) r was 0.882, for
      epithelial cells (EC) r was less than 0.76, for casts r was less than 0.7, while
      correlation between the URISYS 2400 and manual microscopy: for red blood cells r
      was 0.772 and for white blood cells r was 0.771. With the help of Uriaccess (an
      expert system provided by the Sysmex Corporation), 37 rules for microscopic
      review were set up. The review rules were validated, the review rate was less
      than 30% and the false-positive and false-negative results were acceptably low.
      CONCLUSIONS: UF-1000i is capable of reproducible measurement of urine particles
      within the clinically relevant range and shows its advantage over URISYS 2400. It
      is an optimal strategy for urine sample screening using the combination of the
      two methods.

PMID- 23163115
TI  - Assessment of ADVIA Centaur analyzer for the measurement of 25-OH vitamin D.
AB  - BACKGROUND: The aim of the present study was to evaluate some analytical
      performances of the ADVIA Centaur analyzer for the quantitative measurement of 25
      OH Vitamin D [25(OH)D] in serum. METHODS: Serum concentrations of 25(OH)D were
      determined by a new automated chemiluminescence immunoassay method introduced by
      Siemens and adapted to an ADVIA Centaur analyzer, and compared with HPLC and a
      commercial chemiluminescence immunoassay (Liaison DiaSorin). RESULTS: The assay
      displayed a low intra-day (CV < 7.0%) and a low inter-day imprecision (CV <
      9.0%). The ADVIA Centaur demonstrated a stronger Spearman's correlation (r =
      0.921), better agreement (bias = -0.3 ng/mL), and better concordance correlation
      coefficient of Lin (P(c) = 0.88) and better kappa index (k = 0.92) with HPLC,
      than the Liaison DiaSorin assay (r = 0.907, bias = 5.9 ng/mL, p(c) = 0.84, k =
      0.60) with HPLC. On the other hand, a significant inverse relationship was
      observed between parathyroid hormone (PTH) and 25(OH)D concentrations.
      CONCLUSIONS: The ADVIA Centaur method is reliable for routine 25(OH)D
      determination in clinical laboratories

PMID- 23163116
TI  - Exposure of embryos to oxygen at low concentration in a cleavage stage transfer
      program: reproductive outcomes in a time-series analysis.
AB  - BACKGROUND: Embryos are exposed to oxygen at a concentration of 2% to 8% under in
      vivo conditions. Laboratory culture of embryos with oxygen at atmospheric tension
      impairs embryo metabolism and blastocyst development in several species. Indeed,
      a high rate of live births after a day 5 transfer has been obtained by lowering
      oxygen concentration in the incubator atmosphere, thus definitively proving the
      damaging effect of oxygen at atmospheric tension on late stage development of
      human embryos. Conversely, the possible beneficial effect of low oxygen tension
      on assisted reproductive technology (ART) outcomes in a selective cleavage stage
      transfer program remains controversial. Therefore, the present study validated
      the hypothesis that oxygen at reduced concentration may improve ART outcomes when
      cleavage stage embryos are transferred. METHODS: The effect of oxygen at
      atmospheric versus reduced concentration on laboratory and clinical outcomes of
      both in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI)
      cycles were compared. Evaluation of outcomes included fertilization, cleavage,
      and implantation rates. Clinical outcomes were also assessed in our analysis.
      RESULTS: From May 2010 to Mid-October 2010 357 ART cycles (ICSI n = 273 and IVF n
      = 84) were performed using atmospheric oxygen laboratory incubators while from
      Mid-October 2010 until March 2011 306 cycles (ICSI n = 224 and IVF n = 82) were
      carried out under low oxygen concentration. The multi-ovulation protocols were
      not significantly different between the two study periods. The medical and
      laboratory staff, the laboratory, and its procedures and the operating room did
      not differ between the two groups, neither did the culture media. For ICSI
      procedures, no significant difference in ART outcomes was found between the two
      culture conditions. For conventional IVF cycles, both fertilization rate (59 +/-
      36 vs. 71 +/- 32, respectively) and proportion of embryos obtained (38% vs. 50%,
      respectively) were significantly improved under low oxygen condition.
      CONCLUSIONS: Culture of embryos in oxygen at low tension improved ART outcomes
      during a selective cleavage stage transfer program.

PMID- 23163117
TI  - Effects of statin therapy on serum trace element status in dyslipidemic patients:
      results of a randomized placebo-controlled cross-over trial.
AB  - BACKGROUND: Statins are widely used in the management of coronary risk because of
      their efficacy in reducing LDL and their potentially protective pleiotropic
      effects. Imbalances in the status of trace elements such as zinc (Zn) and copper
      (Cu) have been reported to be implicated in the pathogenesis of atherosclerosis.
      The present study investigated the effects of simvastatin on serum Zn, Cu, Zn:Cu
      ratio, selenium (Se), ceruloplasmin (Cp), and superoxide dismutase (SOD) in
      dyslipidemic patients. METHODS: Seventy-seven dyslipidemic patients, who were not
      originally taking lipid lowering agents, were assigned to receive simvastatin (40
      mg/day) and placebo in alternate orders in a double-blind cross-over trial for a
      period of 4 weeks with a 2-week wash-out period. Serum concentrations of Zn, Cu,
      Se, Cp, and SOD were measured before and after each treatment period. RESULTS:
      Statistical analysis did not reveal any significant effect of statin therapy on
      serum concentrations of Zn, Cu, Zn:Cu ratio, Se, Cp, and SOD (p > 0.05).
      CONCLUSIONS: Four-week treatment with simvastatin (40 mg/day) is not associated
      with any beneficial or adverse effect on serum trace element (Zn, Cu and Se)
      status as well as enzymatic activities of Cp and SOD. However, the impacts of
      statin type as well as treatment dose and duration on these parameters remain to
      be clarified.

PMID- 23163118
TI  - B-type natriuretic peptide not TIMI risk score predicts death after acute
      coronary syndrome.
AB  - BACKGROUND: The TIMI risk score is a clinical scoring system used to predict
      mortality in patients following an acute coronary syndrome (ACS). B-type
      natriuretic peptide (BNP) has also been found to be useful in this setting.
      METHODS: 80 patients (35 men, 45 women) mean (SD) age 70.68 (9.90) years with ACS
      were studied. Blood was drawn within 12 hours after the onset of ACS and the
      blood level of BNP was measured using Biosite Triage Cardioprofiler Panel
      (Biosite Inc., San Diego, CA, USA). Patient's TIMI risk score was recorded and
      patients were stratified into low (0 - 2), intermediate (3 - 4), and high-risk (5
      - 7) groups. RESULTS: Overall mortality at 18 months was 20% and was related to
      BNP levels but not the higher TIMI risk scores. Higher BNP levels were related to
      decreased survival (median (range) ng/mL, survivors: 166 (5 - 4,710) vs.
      deceased: 1,093.5 (71.3 - 4,840), p < 0.001). The optimal cutoff for the
      prediction of survival was 250 ng/mL. ACS patients with BNP over this cutoff have
      demonstrated the lower survival (log rank p < 0.001). CONCLUSIONS: BNP
      measurement within the first 12 hours following an ACS is more easily performed
      and is more accurate than a clinical risk score at predicting long term
      mortality.

PMID- 23163119
TI  - Clinical relevance of serum endoglin level in Egyptian hepatocellular carcinoma
      patients.
AB  - BACKGROUND: In hepatocellular carcinoma (HCC), preferential expression of
      endoglin on endothelial cells of the tumor vasculature versus neoplastic cells
      has led to the suggestion that it originates from the neovasculature and plays an
      important role in angiogenesis. Our study aimed to evaluate the role of serum
      endoglin in the diagnosis of HCC and to correlate it with other studied
      prognostic markers. METHODS: Sixty hepatocellular carcinoma patients were
      studied, 60 cirrhotic patients and 45 matched healthy controls. Liver function
      tests, alpha fetoprotein (alphaFP) and serum endoglin levels were determined.
      RESULTS: The study revealed a significant increase in alphaFP and endoglin in
      patients with liver disease compared to controls and in HCC patients compared to
      cirrhotic ones. There was a positive correlation between both biomarkers and
      stages of HCC, whereas no significant correlation between endoglin and alphaFP or
      between both of them and Child Pugh's classification was seen. At a cutoff value
      of 20 ng/mL, the sensitivity of alphaFP was 75% and the specificity was 90%, in
      differentiating HCC from cirrhosis. At a 7.5 ng/mL cutoff, the sensitivity of
      endoglin was 70% and specificity was 65%. On combination of both biomarkers, the
      sensitivity was increased to 85%. CONCLUSIONS: Serum endoglin is a useful
      complementary biomarker in the diagnosis of HCC.

PMID- 23163120
TI  - Changes in diagnosing non-ST-segment elevation myocardial infarction after the
      introduction of a new high-sensitivity cardiac troponin T assay: a single-centre
      experience.
AB  - BACKGROUND: Cardiac troponins are the most sensitive and specific biochemical
      markers of myocardial injury and with the new high-sensitivity troponin methods
      very minor injuries of the heart muscle can be detected. The introduction of high
      sensitivity assays has facilitated reference range adjustments and a revised cut
      off point for myocardial infarction (MI) due to an improved performance in the
      lower concentration range. The objective of this study was to investigate whether
      implementing a high-sensitivity cardiac troponin T (hs-cTnT) assay with
      subsequent lowering of the cut-off point changed the hospital evaluation and
      diagnosis of acute non-ST-segment elevation myocardial infarction (NSTEMI) in a
      general hospital population. METHODS: NSTEMI patients admitted to our hospital
      during two periods each lasting one year were retrospectively compared. During
      period 1 (August 2007 - July 2008) patients were diagnosed with a conventional
      troponin T assay, and during period 2 (August 2009 - July 2010) patients were
      diagnosed using an hs-cTnT assay. RESULTS: A significant increase in the number
      of NSTEMI admissions was observed using the hs-cTnT assay (225 vs. 341, risk
      ratio 1.57, 95% confidence interval 1.33 to 1.85). The proportion of patients
      examined with acute coronary angiography was similar (25.8% vs. 23.8%). Due to
      the higher number of NSTEMI admissions the total number of angiographies was
      higher in period 2 (58 vs. 81, p < 0.05), and significantly more patients were
      examined without signs of coronary artery disease (CAD) (0% vs. 8.6%, p < 0.05).
      A smaller proportion diagnosed with the high-sensitivity assay had significant
      dynamic cTnT changes between the highest and lowest cTnT measurement during each
      admission (96.2% vs. 88.7%, p < 0.01). CONCLUSIONS: More patients were diagnosed
      with NSTEMI and underwent coronary angiography after introducing the hs-cTnT
      assay. At the same time there was an increase in the frequency of coronary
      angiograms without signs of CAD, and fewer had significant dynamic cTnT
      concentration changes.

PMID- 23163121
TI  - High prevalence of Mycoplasma pneumoniae in hepatitis C virus-infected
      hemodialysis patients.
AB  - BACKGROUND: This study investigates the seroprevalence of mycoplasma pneumonia
      (M. pneumoniae) in patients with hepatitis C viral (HCV) infection undergoing
      hemodialysis (HD). METHODS: One hundred and nine HD patients were randomly
      selected from a medical center in Taiwan. Among the subjects, 42 patients (aged
      60.93 +/- 13.94 years) had HCV infection and 67 patients (aged 64.87 +/- 13.02
      years) did not have HCV infection. All subjects were analyzed for serum
      antibodies to HCV and M. pneumonia. Biochemical testing of liver function
      included aspartate aminotransferase (AST), alanine aminotransferase (ALT),
      alkaline phosphatase, and gamma-glutamyl transferase. RESULTS: Seroprevalence of
      M. pneumoniae (p = 0.023) and levels of AST (p = 0.006) and ALT (p < 0.001) were
      significantly higher for HCV seropositive HD patients than for HCV seronegative
      HD patients. HCV seropositive HD patients had a significantly increased risk of
      infection with M. pneumoniae (ORs, 2.475; 95% CIs, 1.099 - 5.571) and high ALT
      level (HAL) (ORs, 5.020; 95% CIs, 1.250 - 20.164, p = 0.018). The serum AST and
      ALT levels of HD patients with HCV and M. pneumoniae infection were significantly
      higher than those of non-HCV and non-M. pneumoniae infected HD patients (p =
      0.017 and p = 0.001, respectively). HAL were observed significantly in HCV
      infection and M. pneumoniae co-infection HD patients (p = 0.023). CONCLUSIONS:
      This study demonstrates that high M. pneumoniae infection in HCV-infected HD
      patients and that it was a factor exacerbating liver dysfunction.

PMID- 23163122
TI  - Maternal plasma advanced glycation end products concentrations in response to
      oral 50-gram glucose load in mid-pregnancy: a pilot study.
AB  - BACKGROUND: Accumulating evidence documents the initiation of diverse physiologic
      and biochemical responses subsequent to an oral glucose load. OBJECTIVES: We
      sought to evaluate the extent to which acute hyperglycemia, resulting from a 50
      gram glucose load, contributes to changes in maternal plasma concentrations of
      advanced glycation end products (AGEs), a heterogeneous group of molecules formed
      from the non-enzymatic reaction of reducing sugars with free amino groups of
      proteins, lipids, and nucleic acids. METHODS: Blood specimens were collected from
      each participant in mid-pregnancy using standard procedures before and after a 50
      gram oral glucose load. Maternal plasma methylglyoxal (MG), pentosidine and
      N(epsilon)-(carboxymethyl)lysine (CML) (free and bound) were measured by HPLC
      MS/MS method. Non-parametric methods were employed for statistical analysis.
      RESULTS AND CONCLUSIONS: Median plasma MG increased 1.27 fold as a result of
      acute hyperglycemia. Median bound CML concentrations were elevated 21% in post
      load plasma samples as compared with pre-load samples, while median free
      pentosidine concentrations were 51% lower (both p-values < 0.05). Future studies
      of larger populations and longer periods of follow-up are warranted to
      investigate the consequences of acute and chronic hyperglycemia on placental
      function and fetal development.

PMID- 23163123
TI  - Elevated levels of serum S100B is associated with the presence and outcome of
      haemorrhagic shock.
AB  - BACKGROUND: Serum S100B was suggested to be elevated after brain damage in
      previous studies. Nowadays, increasing evidence has revealed S100B was also
      elevated in other tissue traumas outside the brain such as bone fracture and
      acute coronary syndrome. The aim of this study is to investigate whether the
      level of serum S100B is associated with haemorrhagic shock (HS), as well as
      multiple organ failure (MOF) and mortality in patients with HS. METHODS: A total
      of 314 patients who had multiple trauma and 132 healthy controls were enrolled in
      this study. Serum levels of S100B were measured using enzyme-linked immunosorbent
      assay during the first 24 hours after injury. RESULTS: The levels of serum S100B
      were significantly elevated in multiple trauma patients with HS compared with
      those without HS and healthy controls. HS patients with MOF had significantly
      elevated levels of serum S100B compared with those without MOF. Furthermore, non
      surviving patients with HS showed significantly higher levels of serum S100B when
      compared with the survivors. Simple linear regression analysis shows that the
      serum levels of S100B were positively correlated with PaO2, Sequential Organ
      Failure Assessment (SOFA), and Acute Physiology and Chronic Health Evaluation
      (APACHE) II score. Only the SOFA score remained significantly associated with
      serum S100B after multiple stepwise regression analyses. CONCLUSIONS: Elevated
      levels of serum S100B could be considered as an independent predicting marker of
      the presence and outcome of HS.

PMID- 23163124
TI  - Occult hepatitis B virus infection in a cohort of Egyptian chronic hemodialysis
      patients.
AB  - BACKGROUND: Replication of hepatitis B virus (HBV) in the absence of a detectable
      hepatitis B surface antigen (HBsAg) and occasionally other HBV serologic markers
      has been called occult hepatitis B infection. As the presence of OBI represents a
      possible threat to those on hemodialysis, being a high risk group, this study was
      carried out to investigate the prevalence of OBI in a cohort of Egyptian patients
      maintained on hemodialysis and to evaluate the protocol of HBV detection in the
      Alexandria Main University Hospital dialysis unit. METHODS: Patients enrolled in
      the study included ninety three HBs-Ag negative Egyptian patients maintained on
      hemodialysis. Liver function tests, serological HBV markers, HCV antibodies, and
      quantification of HBV viral DNA titer were assayed for all participants in the
      study. RESULTS: Twenty five individuals were HBV DNA-positive, representing 26.8%
      of the tested patients. As regards HBV DNA-positive cases, eighteen (72%)
      patients were HCV-Ab positive. Three patients (12%) were positive to both anti
      HBc and anti-HBs and only one patient (4%) was negative to both antibodies.
      Fifteen patients (60%) were positive to anti-HBc only, while 6 patients (24%)
      were positive to anti-HBs only. CONCLUSIONS: OBI is relatively common in Egyptian
      dialysis patients at the Alexandria Main University Hospital dialysis unit, and
      it might be a possible mechanism of transmission of HBV infection between them.
      The protocol implemented in the Alexandria Main University Hospital dialysis unit
      for detection of HBV positive patients should be refined to screening with
      sensitive PCR-based assays for all dialysis patients regardless of biochemical or
      serological findings.

PMID- 23163125
TI  - A girl with 45,X/46,XX Turner syndrome and salt wasting form of congenital
      adrenal hyperplasia due to regulatory changes.
AB  - The incidence of Congenital Adrenal Hyperplasia (CAH) is 1:10,000 - 16,000
      worldwide, of which 90% occurs in the CYP21A2 gene coding for steroid 21
      hydroxylase. On the other hand, Turner's syndrome, with an incidence of 1:2500,
      is a form of gonadal dysgenesis which leads to early ovarian failure and other
      phenotypic changes such as webbed neck, widely-spaced nipples and short stature.
      Here, we present a girl suffering from both 45,X/46,XX Turner's syndrome and salt
      wasting (SW) form of CAH. Clinical and biochemical examinations were performed
      for the patient. Cytogentic studies and molecular testing such as allele specific
      PCR for eight mutations in the CYP21A2 gene, multiplex ligation probe
      amplification (MLPA) and direct sequencing confirmed the clinical diagnosis.
      Heterozygous mutations in the regulatory region at positions -316 to -264
      verified SW form of 21-hydroxylase deficiency. 45,X/46,XX mosaicism proved
      Turner's syndrome. The SW presentation of the patient may be due to the CYP21A1P
      microconversion. The study of regulatory changes of the CYP21A2 and gender
      differentiation pathways would be possible using such patients.

PMID- 23163126
TI  - The effect of perchlorate medication on point-of-care testing.
AB  - BACKGROUND: To create awareness for mismeasurements of ion-selective electrodes
      caused by patients' medications and to prevent severe consequences in an
      intensive care therapy. CASE PRESENTATION: A 73-year-old woman presented with
      severe carbimazol-induced toxic epidermal necrolysis. After replacement of
      carbimazol by sodiumperchlorate, we detected a huge discrepancy in the
      measurement of ionised calcium by two different Point-of-Care (POCT) systems.
      While Siemens Rapidlab 865 showed a severe hypocalcemia at all times, the
      Radiometer 600 system first presented a severe hypercalcemia and, in the course
      of the following days, also a hypocalcemia but with significantly (p < 10 to the 
      45) higher values than the Rapidlab system. Furthermore, the POCT systems
      detected a pseudohypocalcemia at times where we think there was a normo- or even
      hypercalcemia which led to incorrect therapy with excessive substitution of
      ionised calcium. CONCLUSIONS: The substance sodiumperchlorate, which is well
      established in Europe for hyperthyreosis therapy, caused malfunctions of analyses
      of ionised calcium by POCT systems.

PMID- 23163127
TI  - Identification and purification of antigenic 34 kDa outer membrane protein of
      Salmonella typhi.
AB  - BACKGROUND: Salmonella Typhi is a pathogenic bacterium that causes a number of
      infectious diseases such as gastroenteritis and typhoid fever. In this study, an
      antigenic (34 kDa) protein was identified, purified, and characterized from outer
      membrane of Salmonella typhi. METHODS: Immunoblot analysis was used to screen
      antigenic proteins from outer membrane of Salmonella Typhi. Proteins from outer
      membrane were isolated and resolved on SDS-PAGE. In immunoblot analysis, four
      proteins with the following molecular weights of 60 kDa, 54 kDa, 34 kDa, and 26
      kDa were identified as highly antigenic against the serum of patients suffering
      from typhoid fever. One of these outer membrane proteins, with a molecular mass
      of 34 kDa, was selected for this study. The 34 kDa protein was purified and
      characterized by a combination of anion exchange chromatography and gel
      permeation chromatography. The molecular weight of 34 kDa was determined using
      SDS-PAGE electrophoresis. The antigenic nature of the purified 34 kDa protein was
      determined by ELISA against serum proteins of patients suffering from typhoid
      fever and finally confirmed by immunoblot analysis. Antisera against the purified
      34 kDa outer membrane protein of Salmonella typhi was produced and was used to
      recognize the epitope on the surface of an intact Salmonella typhi bacterium.
      RESULTS: The antigenic 34 kDa protein from the outer membrane of Salmonella typhi
      was identified, purified and characterized. The antigenecity of purified protein
      was confirmed by using antibodies present in serum of patient suffering from
      typhoid fever. It was also observed that antibody against 34 kDa outer membrane
      protein recognizes intact Salmonella typhi cells. CONCLUSIONS: It is established
      from the study that 34 kDa protein is antigenic in nature and antibody against
      this protein can also recognize epitopes on intact Salmonella typhi cells.
      Furthermore, this protein can be a good source material to produce vaccine
      against typhoid fever.

PMID- 23163128
TI  - Deterioration of thromboses in primary antiphospholipid syndrome: TNF-alpha and
      anti-annexin A5 antibodies.
AB  - BACKGROUND: To investigate the association between clinical and serological
      features of patients with primary antiphospholipid syndrome (PAPS) and TNF-alpha,
      interleukin 6 (IL-6), and soluble IL-2 receptor (sIL-2R). METHODS: ELISA was used
      for measurement of antibodies (Abs) and TNF-alpha, while IL-6 and sIL-2R were
      measured by chemiluminescence. RESULTS: PAPS patients with pulmonary emboli
      showed positive correlation between IgM isotype of anti-annexin A5 antibodies and
      TNF-alpha (r = 0.894, p = 0.041) and IgM class of anticardiolipin antibodies and
      sIL-2R (r = 0.900, p = 0.037). In PAPS with cerebrovascular insults, positive
      correlation was noticed between TNF-alpha and IgG isotype of anticardiolipin (r =
      0.624, p = 0.040) and anti-annexinA5 Abs (r = 0.768, p = 0.006). CONCLUSIONS:
      Isotype analysis of antiphospholipid and anti-annexin A5 Abs and investigation of
      their association with TNF-alpha is important for differentiation of PAPS
      patients that are prone to further deterioration of arterial and venous
      thromboses.

PMID- 23163129
TI  - Association of fetal but not maternal P-glycoprotein C3435T polymorphism with
      fetal growth and birth weight, a possible risk factor for cardiovascular diseases
      in later life.
AB  - BACKGROUND: The multidrug transporter P-glycoprotein (PGP) is expressed in the
      human placenta. In particular the C3435T ABCB1 polymorphism was associated with
      altered tissue expression of PGP in the human placenta. However, the potential
      functional impact of this polymorphism on the offspring is unknown so far.
      METHODS: We analyzed the impact of the ABCB1/C3435T polymorphism on fetal growth
      in 262 mother/child pairs. Fetal growth was assessed by differential ultrasound
      examination of the fetal body prior to birth and by measuring birth weight.
      RESULTS: The maternal ABCB1/C3435T polymorphism showed no trend for an
      association with birth weight or any ultrasound parameter describing late
      gestational fetal body shape. Genotyping the newborns, however, demonstrated that
      newborns carrying two copies of the T allele had a birth weight of 3176.39 g,
      whereas CT and CC newborns had a birth weight of 3345.04 g (p = 0.022). Adjusting
      for gestational age at delivery, child's gender, maternal BMI, maternal age and
      body weight at delivery confirmed this finding (p = 0.009). Considering
      gestational day of late ultrasound examination, gestational age at delivery,
      child's gender, maternal BMI, maternal age and maternal body weight at delivery,
      the fetal ABCB1/C3435T genotype revealed likewise a significant negative
      correlation with abdominal diameter and abdominal circumference (R2 = 0.538, p =
      0.010 and R2 = 0.534, p = 0.005, respectively). CONCLUSIONS: Low birth weight may
      be a risk factor for cardiovascular diseases in later life. The fetal
      ABCB1/C3435T gene polymorphism may contribute to this risk. Since PGP controls
      transport of various biological agents, we suggest that PGP is involved in the
      transport of biological agents to the fetus that are important for normal fetal
      growth.

PMID- 23163130
TI  - Enzymatic pyruvate measurement by Cobas 6000 open channel assay.
AB  - BACKGROUND: Blood pyruvate measurement in conjunction with lactic acid is useful
      for differentiating pyruvate dehydrogenase deficiencies from primary or secondary
      disorders of mitochondrial electron transport. METHODS: We evaluated the
      analytical performance of pyruvate measurement by an enzymatic open channel assay
      on a Roche Cobas 6000. RESULTS: The assay was linear from 0.07 to 0.50 mmol/L
      pyruvate. Total imprecision ranged from 15.7% to 7.1% at pyruvate levels of 0.08
      to 0.31 mmol/L, respectively. Functional sensitivity was 0.07 mmol/L. The assay
      showed no interference by lipids or bilirubin, whereas haemolysis influenced
      pyruvate concentrations in a hemoglobin concentration-independent manner. Method
      comparison with patient samples (n = 41) showed that the Cobas 6000 enzymatic
      method correlated well (r2 = 0.930) with a similar enzymatic assay on a Cobas
      Mira platform and showed better accuracy in external control schemes.
      CONCLUSIONS: Enzymatic pyruvate measurement by a Cobas 6000 open channel shows
      satisfactory analytical performance. The assay can be integrated in the automated
      laboratory workflow and is always ready for use thanks to its on-board reagents.

PMID- 23163131
TI  - Associations between hepatitis B virus core gene mutations, immune escape and
      clinical presentation.

PMID- 23163132
TI  - Erratum to "IL8 and serum soluble TRAIL levels following anti-VEGF monoclonal
      antibody treatment in patients with metastatic colon cancer" [Clin. Lab. 2012;
      58:501-505].
AB  - BACKGROUND: Colorectal cancer is the third most common human cancer and the third
      leading cause of cancer related death. BevacizumAb is a humanized monoclonal
      antibody developed against vascular endothelial growth factor (VEGF) for the
      treatment of metastatic cancers. Our goal was to evaluate the possibility of
      using serum sTRAIL and IL8 as markers of treatment efficacy and prognosis in
      patients with metastatic colon cancer. METHODS: The study was conducted in
      Denizli between November 10, 2009 and September 20, 2010. 25 patients (6 female,
      19 male) with metastatic colon cancer whose mean age was 58.7 years, were
      selected and included in the study. All patients received therapy with
      BevacizumAb. All patients were followed in the Oncology Clinic of Denizli State
      Hospital and were evaluated by clinical status. sTRAIL and IL8 levels were
      measured by ELISA in the sera of 25 BevacizumAb treated metastatic colon cancer
      patients and 20 healthy age-gender matched controls. Measurements were taken
      before and after treatment. RESULTS: The serum sTRAIL concentrations in patients
      before therapy were similar to those of healthy age-gender matched controls,
      namely 1.23 +/- 0.06 ng/mL and 1.21 +/- 0.04 ng/mL, respectively. After
      BevacizumAb treatment, sTRAIL ratios were increased significantly in 11 of 25
      patients. 14 patients showed progressive disease with median overall survival of
      only 8.1 +/- 0.4 months. These 14 patients were the same ones who showed no
      increase in sTRAIL levels after BevacizumAb treatment. We explored evidence for a
      correlation between sTRAIL levels and overall survival rates and observed that
      elevated sTRAIL levels after the BevacizumAb treatment were significantly
      associated with increased median overall survival up to 22.6 months. Serum IL8
      levels were decreased in all patients who received BevacizumAb therapy.
      CONCLUSIONS: In BevacizumAb therapy, serum IL8 levels were decreased in all
      patients, and thus, changes in such levels were not correlated with disease
      outcome. Our data suggest measurement of changes in sTRAIL following BevacizumAb
      treatment may have prognostic value in metastatic colon cancer patients.

PMID- 23163133
TI  - [A debate of standardized application of concepts as syndrome and pattern].

PMID- 23163134
TI  - [Commentary on syndrome].

PMID- 23163135
TI  - [To establish the syndrome-typing model of psoriasis vulgaris blood-heat syndrome
      based on the set pair analysis method].
AB  - OBJECTIVE: To establish corresponding set pair analysis mathematic model using
      the clinical symptoms of blood-heat type psoriasis vulgaris (BHTPV), thus guiding
      the clinical accuracy of clinical syndrome typing. METHODS: Recruited were 202
      BHTPV with complete data after they were treated by yang subduing blood cooling
      method. Their clinical symptoms and signs were systematically collected. Using
      set pair analysis method, the therapeutic results of cured and markedly effective
      were recruited as the same portion, of effective as the different portion, and of
      ineffective as the contrary portion. The U value of each syndrome factor was
      calculated according to the formula. The correlation factor of syndrome typing of
      BHTPV was screened. The syndrome typing model of BHTPV was established according
      to the correlation factor. RESULTS: The main factors of BHTPV included the scale
      integral > 2.04, the erythema integral > 2.34, age > 50 years old, the area
      integral > 2.07, dry mouth, slippery pulse, yellowish fur, soggy pulse, dry and
      hard stool. The secondary factors included less sweat, insomnia, frequent pulse,
      any infiltration, erythra of any area, red tongue, depression, the disease course
      ranging 1-360 months, age ranging 16-50 years old, string-tight pulse, thin fur,
      the area integral ranging 0-2.07, white fur, purplish tongue, the scale integral
      ranging 0+ -2.04, and feeble pulse. The third factors included the erythema
      integral ranging 0-2.34 and pale red tongue. The set pair analytical model of BHT
      PV was as follows: U = sigma An/N + sigma B(m)i/M + sigma C(p)j/P. CONCLUSIONS: U
      blood-heat syndrome > or = 0.75 could be judged as blood-heat syndrome.
      Satisfactory efficacy could be achieved by blood cooling method. For patients
      with U blood-heat syndrome < 0.75, no satisfactory efficacy could be achieved by
      blood cooling method alone since they were accompanied with other syndrome types.

PMID- 23163136
TI  - [The screening and the functional pathway analysis of differential genes
      correlated with coronary heart disease of blood stasis syndrome].
AB  - OBJECTIVE: To explore the function and target pathway of the correlated
      differential gene of coronary heart disease (CHD) of blood stasis syndrome (BSS).
      METHODS: Patients of the genealogical CHD of BSS (group A) and the genealogical
      CHD of non-BSS (group B), the genealogical non-CHD of BSS (group C), the
      genealogical healthy subjects (group D), the non-genealogical CHD of BSS (group
      E), the non-genealogical healthy subjects (group F) were recruited in this study.
      The differential gene expression spectrums were studied using gene chip
      technique. The molecular functions of differential genes were analyzed and
      illustrated by gene ontology (GO) analysis. The differential gene pathways were
      found out at BioCarta and KEGG. The meaningful target pathways were screened by
      hypergeometric distribution statistical method. The differential genes were
      verified using Real-time fluorescent quantitative PCR. RESULTS: (1) By screening
      the gene chip data (with FC > or =3), we found the expressions of differential
      genes of CHD of BSS were mainly involved in chemokine, interleukin cytokine,
      alexin system, matrix metal proteinase system, fibroblastic growth factor,
      endothelial cell adhesion molecule, and so on. (2) By GO analysis of related
      differential genes (P < 0.05), we found the molecular functions of differential
      genes associated with CHD BSS. (3) By BioCarta and KEGG pathway analysis, we
      found the target pathways of the hereditary correlated differential genes of CHD
      BSS with significance were mainly involved in inflammation, plaque formation,
      endothelial injury, and so on. The results of Real-time fluorescent quantitative
      RT-PCR proved the accuracy of the gene chip. CONCLUSION: The hereditary
      correlated differential genes of CHD BSS were closely associated with
      inflammation, plaque formation, and endothelial injury.

PMID- 23163137
TI  - [The Chinese medicine syndrome features of ulcerative colitis by using
      fluorescence intensity of auto fluorescence imaging].
AB  - OBJECTIVE: To study the Chinese medicine (CM) syndrome features of ulcerative
      colitis (UC) by using fluorescence intensity (the ratio of green to red, G/R
      ratio) of auto fluorescence imaging, thus providing objective evidences for the
      CM syndrome typing of UC. METHODS: Totally 49 patients were recruited. They were
      typed as Dachang damp-heat syndrome (19 cases), Pi-Wei qi deficiency syndrome (30
      cases), and the healthy control group (21 cases) on the bases of mucosal
      morphology of white light endoscopy (WLE) and the G/R ratio of AFI. RESULTS:
      Compared with the healthy control group (1.227 +/- 0.137), the G/R ratio in
      Dachang damp-heat syndrome (0.915 +/- 0.114) and Pi-Wei qi deficiency syndrome
      (1.147 +/- 0.137) decreased with statistical difference (P < 0.05, P < 0.01). Of
      them, it was lower in Dachang damp-heat syndrome group (P < 0.01). The case
      number was mainly dominated in moderate endoscopic index (EI) (11 cases) and
      severe EI (5 cases) in Dachang damp-heat syndrome group. The case number was
      mainly dominated in the remission phase (17 cases) and mild EI (7 cases) in Pi
      Wei qi deficiency syndrome group. The G/R ratio of the remission phase was higher
      than that of the active phase (1.220 vs. 0.963, P < 0.01). There was statistical
      difference in the G/R ratio of the mild EI (1.044), the moderate EI (0.967), and
      the severe EI (0.830) (P < 0.01). CONCLUSIONS: The inflammation degree of Dachang
      damp-heat syndrome was more severe than that of Pi-Wei qi deficiency syndrome.
      AFI could better reflect the inflammation degree of UC.

PMID- 23163138
TI  - [Clinical research of Chinese medicine syndromes of hyperlipidemia inpatients].
AB  - OBJECTIVE: To study the Chinese medicine (CM) syndrome typing of hyperlipidemia
      inpatients, thus exploring the CM syndrome typing laws. METHODS: The clinical
      materials, including blood lipids, grading,complications, CM symptoms, and
      manifestations of tongue and pulse were recorded using self-formulated
      epidemiological questionnaire of CM syndrome in hyperlipidemia, and then these
      materials were statistically analyzed. RESULTS: Gan-qi stagnation syndrome
      (66.46%) was the most often seen syndrome in the 316 hyperlipidemia inpatients.
      Gan stagnation Pi-deficiency syndrome (35.44%), Gan-Shen yin deficiency syndrome
      (16.77%), Pi-Shen yang deficiency syndrome (13.61%), inner stagnation of phlegm
      and stasis syndrome (13.29%), hyperactivity of yang and hypoactivity of yin
      syndrome (9. 18%) were 5 common syndromes of hyperlipidemia. Gan stagnation Pi
      deficiency syndrome occupied an important position among all types and at various
      levels. Results from the lipid classification of hyperlipidemia showed that mixed
      type with low HDL-C was the most often seen (108/316, 34.18%), followed by mixed
      hyperlipidemia (81/316, 25.63%). Totally the mixing type accounted for 59.81%
      (189/316), higher than hypertriglyceridemia (16.77%) and hypercholesterolemia
      (23.42%). CONCLUSIONS: Gan stagnation pi-deficiency syndrome might be the core
      syndrome affecting the lipid metabolism of hyperlipidemia. Mixed hyperlipidemia
      was the most often seen in clinics. Clinical medication should cover actions of
      decreasing TC and TG, and increasing HDL-C.

PMID- 23163139
TI  - [Exploration of the correlation between Chinese medicine syndrome types of
      verrucous gastritis and the pressions of gastric mucosal hypoxia-inducible factor
      1alpha as well as downstream molecules].
AB  - OBJECTIVE: To study the expressions changes of gastric mucosal hypoxia-inducible
      factor-1alpha (HIF-1alpha) and downstream molecules [such as vascular endothelial
      growth factor (VEGF) and cyclooxygenase-2 (COX-2)] of verrucous gastritis (VG)
      patients of different Chinese medicine (CM) syndrome types and their clinical
      significance. METHODS: Totally 94 VG patients were assigned to Gan-Wei disharmony
      group (GWDG, 28 cases), the damp-heat in Pi-Wei group (DHPWG, 17 cases), the
      blood stasis in Wei-collateral group (BSWCG, 20 cases), and the insufficiency of
      Pi-yang group (IPYG, 29 cases). Another 30 patients with chronic mild non-active
      superficial gastritis patients accompanied with negative Hp infection were
      recruited as the control group. The Hp infection was detected using 14C-labeled
      urea breath test. The expressions of HIF-1alpha, VEGF, and COX-2 in the gastric
      mucosal tissue were detected using immunohistochemical EnVision two-step test.
      RESULTS: The positive Hp infection rate in VG patients was 37.23% (35/94 cases).
      The positive Hp infection rate in patients of DHPWG (76. 47%) was significantly
      higher than the other three groups (32.14% in GWDG, 31.03% in IPYG, and 20.00% in
      BSWCG, P < 0.01). The expressions of HIF-1alpha and COX-2 in VG patients of
      different syndrome types were obviously higher than those of the control group (P
      < 0.01, P < 0.05). Of them, the expression of HIF-1alpha was the highest in BSWCG
      and the expression of COX-2 was the highest in DHPWG. The expression of VEGF was
      higher in DHPWG and IPYG than in the control group and the GWDG (P < 0.01, P <
      0.05). CONCLUSIONS: The expressions of HIF-1alpha, VEGF, COX-2, and Hp infection
      showed certain changes in VG patients of different syndrome types. The expression
      of HIF-1alpha was the strongest in BSWCG. The expressions of VEGF and COX-2 as
      well as Hp infection were the highest in DHPWG. All showed the specificity of CM
      syndromes.

PMID- 23163140
TI  - [The oral microbial fingerprint on the greasy tongue coating of patients with
      chronic gastritis].
AB  - OBJECTIVE: To investigate the microbial changes on the greasy tongue coating of
      the patients with chronic gastritis and to explore the formation mechanism of
      greasy tongue coating. METHODS: Forty cases of tongue coating samples from
      patients with chronic gastritis were collected, 20 cases of greasy fur (as the
      greasy fur group), 20 cases of non-greasy fur (as the non-greasy fur group), and
      20 cases of tongue coating samples from healthy subjects (as the healthy control
      group). Using 16S rRNA gene denatured gradient gel electrophoresis (DGGE) the
      microbial population of the tongue coating was detected. The DGGE fingerprint of
      the bacterium on the tongue coating was obtained. After digitalized principle
      component analysis (PCA) and partial least squares (PLS-DA) were performed.
      RESULTS: The microorganism compositions are different in the greasy fur group,
      the non-greasy fur group, and the healthy control group. (1) There were five
      significantly different bands between the greasy fur group and the non-greasy fur
      group, with the accuracy of 97.5% in judging the model. There were 8
      significantly different bands between the greasy fur group and the healthy
      control group, with the accuracy of 95.0% in judging the model. There was no
      obvious difference between the healthy control group and the non-greasy fur
      group. (2) The brightness of band 8 was higher in the greasy fur group than in
      the non-greasy fur group and the healthy control group. It may be a new species
      closely associated with the formation of greasy tongue coating. Results of the
      sequence showed its nearest neighbor was Moraxella catarrhalis, but with the
      similarity of 96.2%. The brightness of band 10 was sequenced as the healthy
      control group > the non-greasy fur group > the greasy fur group. Results of the
      sequence showed it had 100.0% similarity to Rothia mucilaginosa (stick-slip Ross
      strain). CONCLUSIONS: The bacteria species on band 8 may have a close correlation
      with the formation of greasy fur of chronic gastritis, while the bacteria species
      on band 10 may have a close correlation with the formation of non-greasy fur.
      They indicated the microbial changes in the oral cavity may be one of the
      formation mechanisms for greasy tongue coating.

PMID- 23163141
TI  - [Clinical trial of treating stress-induced hyperglycemia patients with sepsis by
      supplementing QI, nourishing yin, and promoting blood flow].
AB  - OBJECTIVE: To investigate the effects of the treatment of supplementing qi,
      nourishing yin, and promoting blood flow (SQNYPBF) on the serum levels of CRP,
      TNF-alpha, IL-1 and IL-6, as well as the expression of HLA-DR in the peripheral
      monocytes in septic patients suffering from stress-induced hyperglycemia.
      METHODS: In the prospective randomized controlled study, eighty-five stress
      induced hyperglycemia patients with sepsis were randomly assigned to the
      experimental group (45 cases) and the control group (40 cases). On the basis of
      routine therapies, including anti-infection, nutrition support, and the glucose
      control with insulin pump, patients in the experimental group additionally
      received the treatment of SQNYPBF (They were intravenously dripped with Shenmai
      Injection and Sulfotanshinone Sodium Injection, once daily, for 7 successive
      days). The serum levels of CRP, TNF-alpha, IL-1, and IL-6 and the HLA-DR
      expression of the peripheral monocytes were detected using ELISA before treatment
      and on the 8th day of the treatment. The total dose and the duration of insulin
      used, the morbidity of hypoglycemia, the APACHE II scores, and the mortality
      within 28-day hospitalization were compared between the two groups. RESULTS: The
      total dose of insulin used, the duration of insulin used, the morbidity of
      hypoglycemia, the APACHE II score on the 8th day of treatment, and the mortality
      within 28-day hospitalization significantly decreased in the experimental group,
      when compared with the control group (P < 0.05, P < 0.01). There was no
      difference in the expression of HLA-DR, the serum levels of CRP, TNF-alpha, IL-1,
      or IL-6 before treatment between the two groups (P > 0.05). After treatment the
      serum levels of CRP, TNF-alpha, IL-1, and IL-6 significantly decreased (P < 0.05)
      and the expression of HLA-DR significantly increased in the two groups (P <
      0.05). Better effects were shown in the experimental group (P < 0.05, P < 0.01).
      CONCLUSION: SQNYPBF combined intensive insulin therapy could better improve the
      sepsis patients' immunity, decrease the plasma glucose level and duration,
      increase their survival rate, and improve their prognosis.

PMID- 23163142
TI  - [Clinical observation on the disease course of chronic renal failure intervened
      by qudu granule].
AB  - OBJECTIVE: To observe the disease course of chronic renal failure (CRF)
      intervened by Qudu Granule (QG) and to explore its possible mechanism. METHODS:
      Totally 166 phase 3 and 4 chronic kidney disease (CKD) patients of Pi-Shen
      deficiency and phlegm-turbidity obstruction syndrome were randomly assigned to
      two groups, the experimental group (83 cases, completed in 77 cases) and the
      control group (83 cases, completed in 75 cases). Based on the routine treatment,
      patients in the experimental group orally took QG, while those in the control
      group orally took niaoduqing granule (NG), 5 g each time, 3 times a day in both
      groups. The total therapeutic course was over 12 months for all. The changes of
      serum creatinine (SCr) were observed in the two groups. The reciprocal of SCr was
      taken as the vertical coordinate, and the course of disease (months) as the
      horizontal coordinate. The oblique rate and the return coefficient (value b) were
      compared between the two groups. Meanwhile, the changes of blood pressure, 24-h
      urinary protein quantitative amount, plasma albumin (Alb), and hemoglobin (Hb)
      were also observed. RESULTS: The average treatment time was longer in the
      experimental group [(42.8 +/- 18.5) months] than in the control group [(34.2 +/-
      12.7) months, P < 0.01]. In the experimental group 35 patients didn't reach the
      endpoint at the 48th month, accounting for 45.45%, while 24 patients didn't reach
      the endpoint in the control group, accounting for 32.00%, showing statistical
      difference (P < 0.01). The b value was -0.00258 +/- 0.00132 in the experimental
      group and -0.00386 +/- 0.00167 in the control group. The absolute value of the
      slope rate was obviously smaller in the experimental group than in the control
      group (P < 0.01). The 48-month blood pressure was obviously lower in the
      experimental group than in the control group. The 24-h urinary protein at the
      12th, 24th, 36th, and 48th month were obviously lower in the experimental group
      than in the control group at the same time point (P < 0.05). The plasma Alb was
      obviously higher in the experimental group than in the control group at the same
      time point with statistical difference (P < 0.05). There was no statistical
      difference in the Hb level between the two groups at each time point (P > 0.05).
      CONCLUSIONS: The course of CRF could be postponed by QG. Its mechanisms might
      possibly be correlated with lowering blood pressure, reducing the excretion of
      urinary protein, and increasing plasma Alb.

PMID- 23163143
TI  - [Clinical observation on the prevention and treatment of perioperative delayed
      cerebrovasospasm in patients with aneurysmal subarachnoid hemorrhage by the
      comprehensive protocol of integrative medicine].
AB  - OBJECTIVE: To investigate the efficacy and safety of the comprehensive protocol
      of integrative medicine in preventing and treating perioperative delayed
      cerebrovasospasm (DCVS) in patients with aneurysmal subarachnoid hemorrhage
      (aSAH). METHODS: Using a prospective randomized controlled trial design, 63 aSAH
      inpatients were assigned to the treatment group (31 cases, 24 treated by
      intervention treatment and 7 by craniotomy) and the control group (32 cases, 26
      treated by intervention treatment and 6 by craniotomy). All patients were treated
      with basic therapy and nimodipine. Those in the treatment group additionally took
      naomai jiejing decoction No. 1 and No. 2. The incidence and the mortality of
      DCVS, re-bleeding, hydrocephalus were compared on the 180th day. The middle
      cerebral artery mean flow velocity (Vm), PI value, linde-gard index on day 1, 3,
      7, and 14 were compared. The Chinese medicine syndrome score, NIHSS, and revised
      Rankin questionnaire on day 1, 14, and 180 were compared. RESULTS: The DCVS
      occurred in 9 cases (29. 0%) of the treatment group and 17 patients (53.1%) of
      the control group, showing statistical difference (P < 0.05). The occurrence of
      re-hemorrhage was obviously lower in the treatment than in the control group
      (3.2% vs. 6.2%), showing statistical difference (P < 0. 05). There was no
      statistical difference in the mortality (6.4% vs. 9.4%) or the occurrence of
      hydrocephalus (29.0% vs 25.0%, P > 0.05). The Vm, PI, and linde-gard index on day
      7, the Vm and linde-gard index on day 14 were obviously lower in the treatment
      group than in the control group (P < 0.05). The Chinese medicine syndrome score
      and NIHSS on day 14 and 180 were lower in the treatment group than in the control
      group, showing statistical difference (P < 0.05). CONCLUSION: The comprehensive
      protocol of integrative medicine could reduce the incidence of aSAH patients'
      DCVS, the Chinese medicine syndrome score and NIHSS, and improve their clinical
      symptoms.

PMID- 23163144
TI  - [Clinical observation of treating osteoporosis vertebral compression fracture of
      senile patients by restitution combined percutaneous vertebroplasty].
AB  - OBJECTIVE: To explore the methods and therapeutic efficacy of restitution
      combined with percutaneous vertebroplasty (PVP) for treating osteoporosis
      vertebral compression fracture (OVCF). METHODS: Recruited were 132 senile
      patients with OVCF who were willing to receive minimally invasive therapy were
      assigned to the comprehensive treatment group and the percutaneous kyphoplasty
      (PKP) group. The 89 vertebral bodies in the 68 cases of the comprehensive
      treatment group received restitution combined with PVP, while the 81 vertebral
      bodies in the 64 cases of the control PKP group received PKP alone. All patients
      completed the follow-ups for more than 3 years. The therapeutic efficacy was
      assessed using visual analogue scale (VAS), Oswestry disability index (ODI),
      Cobb's angle, the height ratios of the diseased vertebral anterior edge and
      middle edge. The operation time for a single centrum, the perspective time during
      the operation, the incidence of bone cement leakage, the injection rate of the
      bone cement, the cost of hospitalization, and the hospital days were compared
      between t he comprehensive treatment group and the PKP group. RESULTS: Compared
      with before treatment in the same group, the VAS and ODI were significantly
      lower, the height ratios of the diseased vertebral anterior edge and middle edge,
      and the Cobb's angle were obviously improved in the two groups, showing
      statistical difference (P < 0.01). There was no significant difference in the
      aforesaid indices between the two groups after treatment at the same time point
      (P > 0.05). There was no significant difference in the incidence of bone cement
      leakage, th e injection rate of the bone cement, or the hospital days between the
      two groups (P > 0.05). But the operation time f or individual vertebral body, the
      perspective time during the operation, and the cost of hospitalization were
      obviously less in the comprehensive treatment group than in the PKP group (P <
      0.01). CONCLUSIONS: Restitution combined PVP could achieve the same therapeutic
      efficacy as that of the PKP. It could effectively restore the diseased vertebral
      height and correct the spinal kyphosis. Besides, there was no statistical
      difference in the incidence of bone cement leakage.

PMID- 23163145
TI  - [Study on the correlation between single nucleotide polymorphism of monoamine
      oxidase A gene and anger regulation].
AB  - OBJECTIVE: To study the correlation between single nucleotide polymorphism (SNP)
      of monoamine oxidase A gene (MAOA) and anger regulation. METHODS: Enrolled were
      healthy students from some college, including 225 of the high trait anger and 221
      of the low trait anger. Subjects were recruited referring to the state-trait
      anger expression inventory 2 (STAXI-2) and their blood sampled. The DNA was
      extracted using phenol-chloroform method, 4 tag SNPs of MAOA (rs5906957,
      rs2235186, rs1181275, and rs5905613) were genotyped by PCR-based ligase detection
      reaction (PCR-LDR). The scores for trait anger expression inventory and the
      scores for trait anger expression control at the 4 tag SNPs of MAOA in the
      different sexes groups of the high and the low trait anger were statistical
      analyzed. RESULTS: There was statistical difference in anger control score of
      locus rs2235186 of MAOA gene group (P = 0.037). There was no significant
      difference in anger expression or anger control score of different genotypes of
      the other three tag SNPs (P > 0.05). CONCLUSION: MAOA gene tag SNP rs2235186 was
      correlated with anger control traits of healthy female college students of the
      low trait anger in China.

PMID- 23163146
TI  - [Contrast study of acupuncture anesthesia and local anesthesia: their effects on
      the blood pressure and the heart rate in chronic rhinitis patients accompanied
      inferior turbinate hypertrophy in low temperature radiofrequency ablation].
AB  - OBJECTIVE: To compare the effects of acupuncture anesthesia (AA) and local
      anesthesia (LA) on the blood pressure (BP) and the heart rate (HR) in chronic
      rhinitis patients accompanied inferior turbinate hypertrophy in low temperature
      radiofrequency ablation (RFA). METHODS: Totally 61 chronic rhinitis patients
      accompanied inferior turbinate hypertrophy were randomly assigned to the AA group
      (31 cases) and the control group (30 cases). All patients received RFA
      respectively under AA and RA. Their heart rate (HR), systolic pressure (SP),
      diastolic pressure (DP), and mean pressure (MP) were recorded and compared at 10
      minutes after their entry into the operating room, immediately before surgery,
      intraoperation, and 5 min after operation. RESULTS: When compared with the
      control group at the same time points, the SP, DP, MP, and HR all decreased at
      intraoperation and 5 min after operation in the AA group. There was statistical
      difference in the SP on the right side at the 2nd melting point and the HR on the
      left side at the 2nd melting point between the two groups (P < 0.05). Compared
      with the same group at 10 min after entry into the operating room, the SP on the
      right side at the 1st melting point, the SP, DP, and MP on the right side at the
      2nd melting point, the SP, DP, and MP on the left side at the 1st melting point,
      and the SP on the left side at the 2nd melting point all obviously increased with
      statistical difference (P < 0.05, P < 0.01). When compared with the same group at
      10 min after entry into the operating room and immediately before surgery, there
      was no statistical difference in the SP, DP, MP, or HR of the AA group at
      intraoperation and 5 min after operation (P > 0.05). When compared with the same
      group at 10 min after entry into the operating room and immediately before
      surgery, there was no statistical difference in HR of the control group at
      intraoperation and 5 min after operation (P > 0.05). CONCLUSION: Patients
      undergoing AA had less fluctuation of the BP and the HR, indicating AA had better
      analgesic effects.

PMID- 23163147
TI  - [Analysis of the dynamic changes of blood hormone levels in H22 liver cancer mice
      of poisonous pathogenic factors syndromes to different degrees].
AB  - OBJECTIVE: To study the dynamic changes of blood hormone levels in H22 liver
      cancer mice of poisonous pathogenic factors syndromes (PPFS) to different
      degrees. METHODS: Two hundred and twenty mice were injected with H22 tumor cells
      from their armpits. On the ninth day after inoculation the mice of severe
      poisonous pathogenic factors syndrome (SPPFS) and of mild poisonous pathogenic
      factors syndrome (MPPFS) were screened. Besides, another normal control group
      consisting of 30 mice was set up. The mice were killed on the tenth and eleventh
      day after inoculation (as the 1st and 2nd time window). The weight of the tumor,
      the wet weight of the thymus and the spleen were weighed. The plasma
      adrenocorticotropic hormone (ACTH), corticosterone, aldosterone, thyroid hormone
      T3 and T4, testosterone, TNF-alpha, and IFN-gamma were detected by ELISA. All the
      aforesaid laboratory parameters were analyzed. RESULTS: The tumor weight was
      obviously larger in mice of the SPPFS group than in those of the MPPFS group at
      the same time window (P < or = 0.05). Compared with the normal control group, the
      thymus was obviously atrophied (P < or = 0.05), the spleen was significantly
      enlarged (P < or = 0.05), the plasma ACTH significantly increased (P < or = 0.05)
      in the SPPFS group at the two time windows. But the increment of ACTH was less in
      the MPPFS group. The plasma corticosterone showed similar tendency as that of
      ACTH. At the 1st time window the plasma testosterone significantly increased in
      the two groups (P < or = 0.05). The plasma testosterone and T4 showed a
      decreasing tendency in the SPPFS group. The plasma TNF-alpha and IFN-gamma levels
      showed an increasing trend in the two groups. Correlation study showed that the
      degree of PPFS was negatively correlated with qi deficiency (r = -0.766, P < or =
      0.05) and T4 (r = -0.738, P < or = 0.05). The degrees of PPFS was positively
      correlated with the plasma ACTH level (r = 0.635, P < or = 0.05). The degree of
      qi deficiency was positively correlated with yang heat syndrome (r = 0.632, P <
      or = 0.05). The plasma ACTH was negatively correlated with T4 (r = -0.504, P < or
      = 0.05). The plasma testosterone was positively correlated with TNF-alpha (r =
      0.619, P < or = 0.05). CONCLUSIONS: PPFS occurs naturally and shows difference to
      different degrees in the development of H22 liver cancer. The disorders of
      neuroendocrine hormones and the suppression of the immune function show dynamic
      changing trends.

PMID- 23163148
TI  - [Effects of qingchang huashi recipe on the dendritic cells of the colonic mucosa
      and the mesenteric lymph nodes in experimental colitis rats].
AB  - OBJECTIVE: To observe the effects of qingchang huashi recipe (QHR) on the
      dendritic cells (DCs) of experimental colitis rats, thus exploring its possible
      mechanisms for treating ulcerative colitis (UC). METHODS: The UC rat model was
      induced by TNBS/anhydrous alcohol. Forty male Wistar rats were randomly divided
      into 4 groups, i.e., the normal group, the model group, the QHR group, and the
      Mesalazine group, 10 in each group. Since the 2nd day of modeling, corresponding
      medication was respectively administered to each treatment group by gastrogavage
      for 10 successive days. The number of DCs in the colonic mucosa was observed
      using iMmunohistochemical assay. The DCs ratio in the mesenteric lymph nodes, and
      the expressions of surface molecules MHC-II and CD86 were detected using flow
      cytometry. RESULTS: Compared with the model group, the number of DCs in the
      colonic mucosa significantly decreased, the expression of MHC-II in the
      mesenteric lymph nodes significantly decreased in the QHR group and the
      Mesalazine group, showing statistical difference (P < 0.01). There was no
      statistical difference between the two groups (P > 0.05). There was no
      statistical difference in the DCs ratios and the CD86 expression among the 4
      groups (P > 0.05). CONCLUSION: QHR could decrease the infiltration of DCs in the
      colonic mucosa, and suppress the activation of DCs in the mesenteric lymph nodes,
      which might be one of its mechanisms for treating UC.

PMID- 23163149
TI  - [Antiulcer effects and mechanism study of Veronicastrum axillare on ethanol
      induced gastric ulcer rats].
AB  - OBJECTIVE: To study the antiulcer effects and the mechanism of Veronicastrum
      axillare (Sieb. et Zucc) Yamazaki (VAY) on ethanol induced gastric ulcer rats.
      METHODS: Totally 48 healthy SD rats were randomly divided into 6 groups, i.e.,
      the normal group, the model group, the ranitidine group, the high dose VAY group,
      the medium dose VAY group, and the low dose VAY group, 8 in each group. Rats in
      the normal group and the model group were administered with normal saline
      respectively. Rats in the ranitidine group were administered with 0.18%
      ranitidine suspension (at the daily dose of 0.027 g/kg) by gastrogavage. Those in
      the high dose VAY group, the medium dose VAY group, and the low dose VAY group
      were administered with VAY at the daily dose of 2.8 g/kg, 1.4 g/kg, and 0.7 g/kg
      by gastrogavage, once daily for 14 consecutive days. The gastric ulcer model was
      established using absolute ethanol after the last gastrogavage. The ulcer index
      and the ulcer inhibitory rate were compared. The concentrations of
      malonyldialdehyde (MDA), nitric oxide (NO), epidermal growth factor (EGF), and
      the activity of superoxide dismutase (SOD) in the serum and the homogenate of the
      gastric mucosa tissue were detected. RESULTS: Compared with the model group, the
      gastric ulcer index in the rest groups obviously decreased (P < 0.01). The ulcer
      index was dose-dependent with VAY (P < 0.01), with the highest gastric ulcer
      index shown in the high dose VAY group (P < 0.01). Compared with the normal
      group, the concentrations of MDA and NO significantly increased in the serum and
      the gastric mucosa tissue, the activity of SOD and the EGF content in the gastric
      mucosa tissue of rats in the model group significantly decreased (P < 0.01).
      Compared with the model group, the MDA concentrations in the serum and the
      gastric mucosa tissue decreased, the serum NO content increased, the NO content
      in the gastric mucosa tissue decreased, the serum SOD activity increased, the EGF
      content in the gastric mucosa tissue increased in the rest groups, all showing
      statistical difference (P < 0.05, P < 0.01). CONCLUSIONS: The water extract of
      VAY had significant effects on ethanol induced gastric ulcer. Its mechanisms
      might lie in reducing the generation of free radicals, promoting the oxygen free
      radical clearance, restraining lipid peroxidation, regulating and controlling the
      in vivo contents of NO and EGF.

PMID- 23163150
TI  - [Effect of extracts from Panax ginseng, Panax notoginseng, and Ligusticum
      chuanxiong on vascular smooth muscle cells of aging and hypertension rats].
AB  - OBJECTIVE: To observe and compare the effects of aging and hypertension on rats'
      aortic vascular smooth muscle cells (VSMCs) and the effects of the extracts from
      Panax ginseng, Panax notoginseng and Ligusticum chuanxiong. METHODS: The rat
      aortic VSMCs model was established using the method of primary cell culture. Of
      them, the rats of the aging experiment were divided into 5 groups, i.e., the
      young control group (as Yon), the old group (as Old), the old + probucol group
      (as Old+Pro), the old +low dose extracts group (as Old+Pro), and the old+high
      dose extracts group (as Old+High). The rats of the hypertension experiment were
      divided into 5 groups, i.e., the Wistar-Kyoto control group (as WKY), the
      spontaneously hypertensive rat group (as SHR), the SHR +Valsartan group (as
      SHR+Val), the SHR+low dose extracts group (as SHR+Low), and the SHR+high dose
      extracts group (SHR+High). The proliferation of VSMCs was detected using MTT. The
      expression of MMP-9 was detected by immunocytochemical assay. The mRNA and
      protein expressions of peroxisome proliferator activated receptor-gamma (PPAR
      gamma) were detected using RT-PCR and Western blot respectively. RESULTS:
      Compared with the Yon group, the proliferation of VSMCs and the MMP-9 expression
      increased, the mRNA and protein expressions of PPAR-gamma decreased in the Old
      group, all showing statistical difference (P < 0.05). Compared with the Old
      group, the proliferation of VSMCs and the MMP-9 expression obviously decreased,
      the mRNA expression of PPAR-gamma obviously increased in the Old+Pro group, the
      Old+High group, and the Old+Low group (all P < 0.05). The PPAR-y protein
      expression obviously increased in the Old+Pro group and the Old+Low group (P <
      0.05). Compared with the WKY group, the proliferation of VSMCs and the expression
      of MMP-9 obviously increased, the mRNA and protein expressions of PPAR-gamma
      obviously decreased in the SHR group (all P < 0.05). Compared with the SHR group,
      the proliferation of VSMCs and the expression of MMP-9 obviously decreased, the
      mRNA and protein expressions of PPAR-gamma obviously increased in the SHR+Val
      group, the SHR+High group, and the SHR + Low group (all P < 0.05). CONCLUSIONS:
      Both aging and hypertension could result in excessive proliferation of rat aortic
      VSMCs and the expression changes of correlated cytoactive factors. The extracts
      from Panax ginseng, Panax notoginseng (Burk.) and Ligusticum chuanxiong can lower
      their proliferation levels and reduce the expressions of negative cytokines, thus
      reducing aging and hypertension induced injury of VSMCs and delaying
      angiocellular aging.

PMID- 23163151
TI  - [The protective function and mechanism of notoginsenoside Rb1 against hypoxia
      hypercapnia-induced pulmonary vasoconstriction].
AB  - OBJECTIVE: To explore the protective function and mechanism of notoginsenoside
      Rb1 against hypoxia hypercapnia-induced pulmonary vasoconstriction (HHPV).
      METHODS: The pulmonary artery smooth muscle cells of healthy male SD rats were
      primarily cultured and the second to the fifth subcultured cells were incubated
      with 8, 40, and 100 mg/L notoginsenoside Rb1 respectively under the hypoxia
      hypercapnia condition (1% O2 and 6% CO2). The cells were harvested for 24 h. The
      phosphated extracellular signal-regulated kinase (p-ERK) protein expression of
      the cells was detected by Western blot. The mRNA expressions of ERK1 and ERK2
      were detected using half quantitative reverse transcription polymerase chain
      reaction (RT-PCR). RESULTS: The expression of p-ERK protein, the mRNA expressions
      of ERK1 and ERK2 were weakly positive in the control group. Their expressions in
      the hypoxia-hypercapnia group were obviously enhanced (P < 0.01). After
      intervention of Rb1 at different concentrations, their expressions were obviously
      lowered (P < 0.05, P < 0.01) in a dose-dependent manner. The optimal effects were
      obtained at the dose of 100 mg/L. The expression of p-ERK protein was
      significantly positively correlated with mRNA expressions of ERK1 and ERK2 in
      notoginsenoside Rbl-treated groups (r = 0.500, P < 0.01; r = 0.977, P < 0.01).
      CONCLUSIONS: ERK1/2 pathway might play a role in the rat HHPV. Notoginsenoside
      Rb, could alleviate HHPV by inhibiting the ERK1/2 pathway.

PMID- 23163152
TI  - [Effects of complement inhibiting component of Ephedra sinica on immunological
      inflammation following acute spinal cord injury in rats].
AB  - OBJECTIVE: To investigate the effects of complement inhibiting component of
      Ephedra sinica on immunological inflammation following acute spinal cord injury
      (SCI) in rats. METHODS: The complement inhibiting component of Ephedra sinica was
      isolated by multiple precipitation steps and thin layer chromatography, and then
      the activity was analyzed. Fifty healthy SD rats were selected and randomly
      divided into the control group and the experimental group, 25 in each group.
      Induction of SCI was performed following a modified Allen's weight-drop method.
      The complement inhibiting component from Ephedra sinica (15 mg/kg) dissolving in
      5 mL normal saline was immediately administered by gastrogavage after SCI, once
      daily. Equal volume of normal saline was administered to rats in the control
      group by gastrogavage. Hematoxylin and eosin (H&E) staining and C3
      immunohistochemical staining were performed in SCI tissue at 12 h, day 1, 3, 7,
      and 14 after SCI. C3 positive expressions and myeloperoxidase (MPO) activity were
      assessed. Intercellular adhesion molecule-1 (ICAM-1) mRNA expression level was
      evaluated by Real-time PCR technique. RESULTS: C3 positive expression, MPO
      activity, and ICAM-1 mRNA level were significantly weaker in the Ephedra sinica
      group than in the control group at all time points (12 h, day 1, day 3, day 7,
      and day 14 after SCI) (P < 0.01, P < 0.05). CONCLUSIONS: There existed complement
      system activation following acute SCI. The complement inhibiting component of
      Ephedra sinica significantly reduced immunological inflammation after SCI, and
      played an important role in secondary SCI.

PMID- 23163153
TI  - [Effects of oxymatrine on the expressions of pro-collagen and fibronectin of
      fibroblasts derived from human hyperplastic scars].
AB  - OBJECTIVE: To study the effects of oxymatrine (OM) on the expressions of pro
      collagen I (PC I), pro-collagen II (PC III), fibronectin (FN), matrix
      metalloproteinase-1 (MMP-1) mRNA of fibroblasts from keloid (KFb), hyperplastic
      scar (HFb), and normal skin (NFb), and to compare with hydrocortisone (HC).
      METHODS: The primary KFb, HFb and NFb were derived from patients and cultured in
      vitro using tissue block culture method. The fibroblasts were treated with 500
      microg/mL OM, 2 microg/mL HC, or without any medicine (as the control). The mRNA
      expressions of PC I, PC III, FN, MMP-1 of the fibroblasts were detected using RT
      PCR. RESULTS: Under the normal condition, when compared with NFb, the mRNA
      expressions of PC I of KFb and HFb increased by 31.7% and 34.2% (both P < 0.05).
      Besides, the mRNA expression of PC III of KFb increased by 44.9% (P < 0.01). OM
      down-regulated the mRNA expressions of FN and PC I of HFb by 18.8% and 23.6%
      respectively (both P < 0.05). HC decreased the mRNA expressions of FN and PC I of
      HFb by 26.8% and 43.6% respectively (P < 0.05, P < 0.01). Meantime, OM up
      regulated the mRNA expression of MMP-1 of KFb by 21.8% (P < 0.05). CONCLUSIONS:
      OM suppressed the synthesis of extracellular matrix (ECM) possibly through down
      regulating the mRNA expressions of PC I and FN. Compared with HC, OM could
      promote the degradation of ECM through inducing the MMP-1 mRNA expressions of
      KFb. Therefore, OM could be potentially used in treatment of hypertrophic scar
      and keloid.

PMID- 23163154
TI  - [Effects of huqi extractum on the viability and apoptosis in mouse thymic
      lymphocytes against 60Co radiation].
AB  - OBJECTIVE: To explore the effects of Huqi Extractum (HQE) on the viability and
      apoptosis in mouse thymic lymphocytes against 60Co radiation. METHODS: Thymic
      lymphocytes were isolated from 4 -8 weeks healthy male Kunming mice and primarily
      cultured. Then they were divided into the control group, the irradiation group,
      the low dose HQE group, the medium dose HQE group, and the high dose HQE group.
      Equal volume of serum free RPMI-1640 culture solution was added in the control
      group and the irradiation group, while equal volume of HQE solution (at the daily
      dose of 25, 50, and 100 mg/mL) was respectively added in the low, medium, and
      high dose HQE groups. Except the control group, those in the rest groups were
      exposed radiation at a single dose of 5 Gy gamma-ray. Changes of the thymic
      lymphocytes' viability were measured by MTT colorimetric assay at 12, 24, 36, and
      48 h after radiation. The early apoptosis rate was detected using flow cytometry
      (FCM) after 10-h radiation. The apoptosis was detected using agarose gel
      electrophoresis to observe the DNA injury after 24-h radiation. RESULTS: The
      viability level decreased more obviously in the irradiation group than in the
      control group at 24 -48 h after radiation (P < 0.01, P < 0.05). The average
      viability level was obviously higher in the low, medium, and high dose HQE groups
      than in the irradiation group (P < 0.05) in a dose dependent manner. The early
      apoptosis rate was obviously lower in the low, medium, and high dose HQE groups
      than in the irradiation group, with statistical difference shown in the high dose
      HQE group (P < 0.01). Typical DNA ladder fragments were found in the
      electrophoresis in all groups except the control group. But the DNA injury was
      comparatively milder in the low, medium, and high dose HQE groups, with more
      obvious effects shown in the high dose HQE group. CONCLUSION: HQE showed
      protection for the viability of early thymic lymphocytes exposed to the 60CO
      radiation, and could lower the early apoptosis level.

PMID- 23163155
TI  - [Effects of wenhua juanbi recipe on the gene expression profile of the synovium
      in collagen-induced arthritic rats].
AB  - OBJECTIVE: To study the effects of Wenhua Juanbi recipe (WJR) on the gene
      expression profile of the synovium in collagen-induced arthritis (CIA) rats, and
      to explore its mechanisms for treating CIA. METHODS: The CIA model was induced by
      intradermal injection of bovine collagen type II emulsion from the tail of 40
      healthy male Wistar rats. Selected 16 successfully modeled rats were randomly
      divided into the model group and the WJR-treated group, 8 in each group. WJR at
      the daily dose of 22.9 g/kg was given to rats in the WJR-treated group by
      gastrogavage, while normal saline was given to those in the model group. Both
      were performed once daily, for 30 successive days. By the end of medication, the
      total RNA was extracted from the synovium of rats in the two groups. The gene
      expression profile of each sample was analyzed using Illumina oligonucleotide
      microarray. RESULTS: Compared with the model group, after the intervention of
      WJR, 222 differentially expressed genes were identified in CIA rats, including 76
      genes up-regulated (such as RatNP-3b and so on) and 146 downregulated (such as
      Angptl 2, Muc1, bcl-2, and so on). The differential genes were mainly involved
      with apoptosis, angiopoietin, defensin gene, cytokine, signal transduction,
      oncogene, etc. CONCLUSION: WJR played a role in treating CIA multi-target
      possibly through regulating and controlling multiple genes expressions. Wenhua
      Juanbi Recipe; collagen-induced arthritis; synovium; gene expression

PMID- 23163156
TI  - [Nonlinear dynamic analysis of electrical signals of wide dynamic range neurons
      in the spinal dorsal horn evoked by acupuncture manipulation at different
      frequencies].
AB  - OBJECTIVE: To study the encoding information of electrical signals of wide
      dynamic range (WDR) neurons in the spinal dorsal horn evoked by acupuncture
      manipulation at different frequencies using nonlinear dynamics analysis. METHODS:
      Microelectrode extracellular recordings were used to observe the WDR neuron
      discharge evoked by acupuncture manipulation at Zusanli point (ST36) with
      different frequencies (0.5, 1, 2, and 3 Hz) in SD rats. The nonlinear dynamics
      analysis method was used to extract the nonlinear characteristic parameters, such
      as interspike interval, the Lyapunov exponent, Lempel-Ziv complexity, and the
      neural coding of the electrical signal evoked by acupuncture manipulations at
      different frequencies. RESULTS: Different characteristics were manifested with
      acupuncture manipulations at 4 different frequencies. More than a simple linear
      correlation was shown between the firing rate of the WDR neurons and the
      frequency of the acupuncture manipulation. The electrical signals evoked by
      acupuncture manipulation at Zusanli point (ST36) showed distinguished chaotic
      features. CONCLUSIONS: It is applicable and feasible to describe and summarize
      the rhythm of the acupuncture electrical signal using the concepts and
      terminology of the nonlinear dynamics. Different acupuncture manipulation methods
      could interfere the transmission, coding, and processing of electrical signals in
      the spinal dorsal horn.

PMID- 23163157
TI  - [Alisol B inhibited complement 3a-induced human renal tubular epithelial to
      mesenchymal transition].
AB  - OBJECTIVE: To study whether alisol B could inhibit complement 3a (C3a) induced
      renal tubular epithelial-mesenchymal transition (EMT). METHODS: The in vitro
      cultured human renal tubular epithelial HK-2 cells were intervened with 5 ng/mL
      transforming growth factor-beta (TGF-beta), 0.1 micromol C3a, and 0.1 micromol
      C3a + 10 micromol alisol B, respectively. The mRNA and protein expressions of
      alpha-SMA, E-cadherin, and C3 were detected using RT-PCR, Western blot, and
      immunofluorescence, respectively. RESULTS: The mRNA and protein expressions of C3
      in HK-2 cells were up-regulated after intervention of C3a (P < 0.01), the mRNA
      and protein expressions of alpha-SMA in HK-2 cells were obviously enhanced (P <
      0.01), the mRNA and protein expressions of E-cadherin obviously decreased (P <
      0.01). When compared with the group intervened by exogenous C3a, after
      intervention of alisol B, the mRNA and protein expressions of alpha-SMA in HK-2
      cells were obviously reduced (P < 0.01), the mRNA and protein expressions of E
      cadherin obviously increased (P < 0.05). CONCLUSIONS: Exogenous C3a could induce
      renal tubular EMT. Alisol B was capable of suppressing C3a induced EMT.

PMID- 23163158
TI  - [The Chinese medicine syndrome typing mode at the same level is the key point to
      explore the syndrome laws of disease. An inspiration from studying Chinese
      medicine syndrome laws of polycystic ovarian syndrome].
AB  - Chinese medicine (CM) syndrome typing methods not only provides information on
      the diagnosis and treatment of diseases, but also embodies the whole process of
      their occurrence, development, and prognosis. Standard syndrome typing methods
      can provide a testing platform for clinical efficacy assessment and scientific
      research work. By my 16 years' clinical experience, inter-group comparison of
      polycystic ovarian syndrome (PCOS) patients of different CM syndrome types at the
      same level (reproductive endocrinology and metabolism) was conducted. They were
      also compared with the healthy subjects. Results showed that homogeneity and
      heterogeneity exist in PCOS patients of different CM syndromes in the
      reproductive endocrine and metabolic characteristics, which is important to
      understand the laws between the pathological changes and syndrome types of PCOS.
      It is also a good inspiration to understand and clarify the correlation between
      the asthenia of Zang-Fu organs in CM theories and PCOS. Therefore, I believe that
      it is necessary to explore the laws of each CM syndrome type at the same level of
      syndrome typing, thus finding out the pathogenesis of PCOS. Only in this way
      could the clinical efficacy and the research level of integrative medicine be
      effectively improved.

PMID- 23163159
TI  - [A new thought of compound compatibility mechanism based on active small
      molecules monoclonal antibodies in herbs].
AB  - Compatibility mechanism study of Chinese herbal compound (CHC) has been one of
      key contents in Chinese medical research, but the present research methods are
      not suitable for its own features due to its complexity, which has restricted the
      process of modernization and intemationalization of Chinese medicine. In this
      paper, we addressed that the compatibility is closely correlated to their in vivo
      metabolic processes. The preparation of active small molecules monoclonal
      antibodies in herbs and testing a variety of effective compositions
      simultaneously using immunoassay can clarify the in vivo metabolism and mutual
      interactions of Chinese herbs, which is a new thought of studying the compound
      compatibility mechanisms.

PMID- 23163161
TI  - [High trait anger is hypothesized to be the main personality characteristics and
      important pathogenic condition for anger induced diseases].
AB  - Through document analysis, high trait anger as the hazard factor for the
      occurrence of many diseases was proposed. The high trait anger should be the main
      personality characteristics and important pathogenic condition for anger induced
      diseases. It is expected to find out more effective treatment and prevention
      pathways for anger induced diseases.

PMID- 23163160
TI  - [The research course and the perspective of molecular regulation network and
      blood stasis syndrome].
AB  - Studying the literature of blood stasis syndrome (BSS), we reviewed the research
      course and the perspective of molecular regulation network and BSS. The essence
      study of BSS was firstly proposed by Chen Ke-ji and Wang Jie, and developed for
      more than thirty years. The course for BSS study mainly included the formulation
      of BSS diagnostic standard, the establishment of BSS animal model, pedigree
      methods, twins combined clinical epidemiological survey of BSS research, the four
      "zu" subjects combined molecular regulation network of BSS, signal transduction
      system network and BSS research, and so on. Along with a new sequencing approach
      in basic research, clinical diagnostics, and drug development, we are promising
      to see the whole gene network research of human diseases, such as metabolic
      disease, cancer, and etc. These achievements could provide a new way of thinking
      for further studying the essence of BSS.

PMID- 23163162
TI  - [Ganoderma spore induced increased CA72-4 in three gastroenteric tumor patients
      and literature analysis].

PMID- 23163164
TI  - [Treatment of PCOS by acupuncture: present experimental and clinical reports].

PMID- 23163163
TI  - [Progress of mechanism studies on quercetin for preventing and treating
      neurodegenerative diseases].

PMID- 23163165
TI  - Exploring my options.

PMID- 23163166
TI  - High aspirations. Zeroing out HAIs.

PMID- 23163167
TI  - In harmony. No hospital is an island in Iowa alliance.

PMID- 23163168
TI  - Green thumb, healthy patients. Greenhouse promotes food as medicine.

PMID- 23163169
TI  - Most wired. Understanding care patterns.

PMID- 23163170
TI  - The quality disconnect.
AB  - Hospitals are under pressure to provide payers and others with more immediate
      access to quality measures. But the data that's being collected now is not
      aligned with how it should and could be collected.

PMID- 23163171
TI  - Improving patient engagement. Interview by Matthew Weinstock.

PMID- 23163172
TI  - Tackling the high cost of chronic disease.

PMID- 23163173
TI  - Patient safety in the OR.

PMID- 23163174
TI  - Closing the gaps in the nation's trauma system.

PMID- 23163175
TI  - The evolution of leadership.

PMID- 23163176
TI  - Confronting a tyranny of violence.

PMID- 23163177
TI  - Pneumonia in Papua New Guinea: lessons learnt for the way forward.

PMID- 23163178
TI  - Some general factors to be considered when implementing a program to control
      pneumonia.

PMID- 23163179
TI  - Pneumonia in Papua New Guinea, from the past to the future.
AB  - This paper briefly describes a journey with pneumonia and the pneumococcus that
      began in partnership with Ian Riley at the Lae Hospital in 1967 and continues 43
      years later. It is a journey that signalled the global emergence of penicillin
      resistant pneumococci and played an important role in the licensure of
      pneumococcal polysaccharide vaccine for use in adults around the world. The
      journey involved many other people whose experience began in Papua New Guinea
      (PNG), playing lead roles in the global program to reduce pneumonia deaths in
      developing countries. But none of this has benefitted Papua New Guineans as it
      could and should have done. In this paper I assert that substantial benefits
      could now follow from widespread use of the 23-valent polysaccharide vaccine in
      PNG adults not suffering from HIV and that there is also good scientific reason
      why children over the age of 9 months should be offered the potential benefits
      from use of this vaccine that were demonstrated in PNG in the 1980s. Indeed there
      are very good medical and economic reasons why it should happen.

PMID- 23163180
TI  - Pneumonia research in Papua New Guinea: 1967-1986.
AB  - Between 1967 and 1985 research on pneumonia in Papua New Guinea (PNG) was
      fundamental not only to standard treatments of disease in PNG, but also to the
      establishment of the World Health Organization's global Program for Control of
      Acute Respiratory Infections. Pneumonia was the leading cause of death in both
      population-based and hospital studies. Research that began in 1967 revealed a
      pattern of disease in adults reminiscent of that seen in industrialized countries
      in the early 20th century. Streptococcus pneumoniae (pneumococcus) was the
      predominant causative organism. Pneumococci were commensals of the upper
      respiratory tract that invaded first the lungs and then the blood stream. Some
      serotypes were more invasive than others and case fatality increased with deeper
      levels of invasion. The pandemic of Hong Kong (H3N2) influenza spread to the
      Southern Highlands in 1969 resulting in 2000 deaths. The conclusion that
      pneumococcal pneumonia had been the principal cause of death led to the
      establishment of a pneumonia research unit in Tari. A field trial of pneumococcal
      polysaccharide vaccine showed the vaccine to be most effective in preventing
      invasive disease. Vaccination reduced pneumonia mortality by 44% in previously
      healthy adults. The epidemiological situation was more complex in children than
      in adults because many different species and serotypes of bacteria could be
      isolated from lung aspirate. Although many of these organisms would normally have
      been regarded as non-pathogenic, S. pneumoniae and Haemophilus influenzae,
      recognized pathogens, were the principal causes of severe morbidity and
      mortality. The same principles of carriage of and invasion by upper respiratory
      commensals applied as much to children as they did to adults, and the rank order
      of invasive serotypes of S. pneumoniae and H. influenzae was the same in
      different age groups. Slow maturation of a child's immune system meant, however,
      that children could be susceptible to invasion by particular serotypes. Infants
      were frequently colonized by pathogenic bacteria within days of birth. Nasal
      discharge, which was extremely common, was most probably a result of domestic
      smoke pollution and low standards of hygiene. Aspiration of infected secretions
      was a likely explanation for the variety of organisms isolated from lung
      aspirate. A trial of pneumococcal polysaccharide vaccine showed the vaccine to be
      effective in preventing death from pneumonia in children 6-9 months of age
      provided pneumonia was not associated with other causes of death; this result was
      shown to be consistent with the principles of infection and invasion described
      above. Principles of antibiotic therapy for child pneumonia were also established
      at this time.

PMID- 23163181
TI  - Pneumonia in Goilala.
AB  - The clinical syndrome of pneumonia in adults in Port Moresby, the capital city of
      Papua New Guinea, has changed from the 1970s to the present. The severe lobar
      pneumonia commonly diagnosed in young adult men, characteristically from Goilala
      and living in settlements in Port Moresby, is no longer seen. Today pneumonia in
      adults is likely to be milder and bronchopneumonic in type. Possible explanations
      for the change include changes in immunity and in the bacteria found in the
      environment and carried in the nasopharynx of recent immigrants to the city. A
      change in treatment-seeking behaviour together with the wide availability of oral
      antibiotics is considered to be the most likely cause of the altered clinical
      syndrome that we have observed.

PMID- 23163182
TI  - Collaborative studies in mucosal immunology in Goroka.
AB  - A collaborative program between the Papua New Guinea (PNG) Institute of Medical
      Research and the Hunter Mucosal Group has completed studies relevant to
      protection of the airways against bacterial infection. Specifically, these
      studies addressed the mucosal capacity to produce local immunoglobulins and the
      capacity of the airways to respond to an oral vaccine containing inactivated
      nontypeable Haemophilus influenzae (NTHi). The mucosal IgA response to NTHi
      antigens was blunted in both children and adults in PNG compared with that found
      in Australian children and adults, whose airways are colonized only
      intermittently. Despite this, when oral NTHi is given to Papua New Guinean adults
      with chronic airways disease, it is followed by a significant (50%) reduction in
      incidence of acute bronchitic episodes, and a 3-log reduction in density of
      colonization, which persisted about 10 months. The implications of these key
      findings are discussed with respect to both mechanism and wider control of
      pathology emanating from abnormal airways colonization in a PNG environment.

PMID- 23163183
TI  - Oxygen supplies for hospitals in Papua New Guinea: a comparison of the
      feasibility and cost-effectiveness of methods for different settings.
AB  - Oxygen therapy is essential in all wards, emergency departments and operating
      theatres of hospitals at all levels, and oxygen is life-saving. In Papua New
      Guinea (PNG), an effective oxygen system that improved the detection and
      treatment of hypoxaemia in provincial and district hospitals reduced death rates
      from pneumonia in children by as much as 35%. The methods for providing oxygen in
      PNG are reviewed. A busy provincial hospital will use on average about 38,000 l
      of oxygen each day. Over 2 years the cost of this amount of oxygen being provided
      by cylinders (at least K555,000) or an oxygen generator (about K1 million) is
      significantly more than the cost of setting up and maintaining a comprehensive
      system of bedside oxygen concentrators (K223,000). A district hospital will use
      17,000 l per day. The full costs of this over 2 years are K33,000 if supplied by
      bedside concentrators, or K333,000 plus transport costs if the oxygen source is
      cylinders. In provincial and district hospitals bedside oxygen concentrators will
      be the most cost-effective, simple and reliable sources of oxygen. In large
      hospitals where there are existing oxygen pipelines, or in newly designed
      hospitals, an oxygen generator will be effective but currently much more
      expensive than bedside concentrators that provide the same volume of oxygen
      generation. There are options for oxygen concentrator use in hospitals and health
      centres that do not have reliable power. These include battery storage of power
      or solar power. While these considerably add to the establishment cost when
      changing from cylinders to concentrators, a battery-powered system should repay
      its capital costs in less than one year, though this has not yet been proven in
      the field. Bedside oxygen concentrators are currently the 'best-buy' in supplying
      oxygen in most hospitals in PNG, where cylinder oxygen is the largest single item
      in their drug budget. Oxygen concentrators should not be seen as an expensive
      intervention that has to rely on donor support, but as a cost-saving intervention
      for all hospitals.

PMID- 23163184
TI  - Improving the aetiological diagnosis of bacterial pneumonia and meningitis in
      Papua New Guinea.
AB  - Bacterial pneumonia and meningitis are major causes of childhood mortality in
      Papua New Guinea (PNG). Laboratory techniques for detection of bacterial
      pathogens have improved in the last decade, particularly molecular techniques
      that can be applied to culture-negative samples. With adequate training and
      support, a number of these techniques are readily available to research staff in
      PNG. In this article we summarize previous studies on the aetiology of pneumonia
      and meningitis in PNG, describe current diagnostic approaches and discuss
      available diagnostic tools to enhance surveillance of bacterial pneumonia and
      meningitis.

PMID- 23163185
TI  - Nontypeable Haemophilus influenzae and childhood pneumonia.
AB  - Nontypeable Haemophilus influenzae (NTHi) is a common microbe frequently isolated
      from the nasopharynx of children. Bacterial pneumonia is a major cause of
      morbidity and mortality in children less than 5 years of age, with the burden of
      disease being greatest in developing countries. Determination of the bacterial
      aetiology of pneumonia is difficult due to sampling constraints. However, with a
      combination of sampling approaches, trans-thoracic fine-needle aspiration, blood
      culture and screened sputum, the evidence strongly suggests that NTHi is a
      significant causative pathogen of pneumonia in young children. However, further
      studies are required. The development of a new pneumococcal conjugate vaccine
      containing H. influenzae protein D has the potential to be beneficial against
      disease caused by NTHi, including pneumonia. With the implementation of this
      vaccine in many regions of the world where NTHi disease is endemic, it will be
      critical to introduce surveillance programs wherever it is used.

PMID- 23163186
TI  - The bacteriology of lower respiratory infections in Papua New Guinean and
      Australian indigenous children.
AB  - Indigenous children in Australia and children in Papua New Guinea (PNG) share a
      high burden of respiratory disease. In PNG the focus has been on pneumonia as a
      major cause of mortality. While pneumonia incidence remains high in Australian
      Indigenous children, improved access to better health care has resulted in
      reduced mortality. However, severe and recurrent pneumonia are risk factors for
      chronic suppurative lung disease or bronchiectasis in Australian Indigenous
      children. Bronchiectasis is associated with significant morbidity, and early
      death in adulthood. This paper includes an outline of the disease manifestations
      of acute and chronic lower respiratory infections. The main bacterial pathogens
      involved in pneumonia, bronchiolitis, bronchitis and bronchiectasis have been
      determined. Capsular organisms such as Streptococcus pneumoniae and Haemophilus
      influenzae type b are more often implicated in acute infections, while chronic
      infections are frequently associated with nontypeable (noncapsular) H.
      influenzae. Moraxella catarrhalis is more often isolated from very young
      children. Possible reasons for the high burden of respiratory disease in Papua
      New Guinean children and Australian Indigenous (primarily Aboriginal) children
      include early and dense colonization with multiple species and strains of
      respiratory pathogens. There is a role for vaccines in preventing lower
      respiratory infection.

PMID- 23163187
TI  - Streptococcus pneumoniae serogroups and colony morphology: a look back.
AB  - From 1985 to 1987, Streptococcus pneumoniae isolates were collected from children
      under 5 years of age in the Asaro Valley, Papua New Guinea as part of a study on
      bacterial colonization and respiratory tract infections. Data on serogroup and
      colony morphology were collected to survey serogroups and associated colony
      morphologies present in the area and to assess whether colony morphology can be
      indicative of serogroup. In total, 5989 colonies were examined; serogroups 6, 10,
      14, 15, 19, 23, 33, 34, 35 and nonserotypeable strains were the most common and
      accounted for 77% of all the colonies, with serogroups 6, 19 and 23 accounting
      for 48%. The majority of colonies displayed the typical draughtsman morphology,
      though serogroup 10 and non-serotypeable isolates most often displayed a raised
      colony morphology. Of the 15 mucoid colonies identified 73% were serotype 3,
      though only 29% of serotype 3 isolates were mucoid. Thus colony morphology is of
      limited value in identifying the pneumococcal serogroup/serotype apart from
      mucoid colonies, which are likely to be serotype 3.

PMID- 23163188
TI  - Human immunodeficiency virus and respiratory disorders: clinical and diagnostic
      considerations.
AB  - Respiratory infections are a major health burden for the people of Papua New
      Guinea (PNG) who are positive for human immunodeficiency virus (HIV). In the face
      of an ongoing HIV epidemic, little is known about the epidemiology and aetiology
      of respiratory infections in people living with HIV in PNG. In this article we
      provide an overview of the most important respiratory pathogens in HIV-positive
      people globally, focusing primarily on adults. Particular attention is given to
      respiratory viruses, bacterial pathogens such as Streptococcus pneumoniae and
      Mycobacterium tuberculosis, and Pneumocystis jiroveci. In doing so we highlight
      the need for a better understanding of the aetiology of respiratory infections in
      HIV-positive people in PNG. A study is underway that aims to determine the
      aetiology of common infectious illnesses in HIV-positive people in PNG, focusing
      on respiratory infections, diarrhoeal diseases and febrile illness. The results
      of this study should guide future prevention, diagnostic and treatment
      strategies.

PMID- 23163189
TI  - Melioidosis--an uncommon but also under-recognized cause of pneumonia in Papua
      New Guinea.
AB  - Melioidosis is being increasingly recognized as an important cause of severe,
      acute community-acquired pneumonia in various tropical regions. The chronic form
      of melioidosis can also mimic tuberculosis. Studies have established that, while
      uncommon in the Port Moresby region, melioidosis is an important cause of
      pneumonia and sepsis in the Balimo region of Western Province. Phylogenetic
      analyses of strains of Burkholderia pseudomallei from Papua New Guinea have shown
      them to be more closely related to strains of B. pseudomallei from Australia than
      to strains from Southeast Asia. This is consistent with the proposed origins of
      B. pseudomallei in Australia, with subsequent spread out of Australia to
      Southeast Asia during the last ice age. Further surveillance across Papua New
      Guinea is likely to unmask other locations where B. pseudomallei occurs in the
      environment and where melioidosis is currently not being diagnosed.

PMID- 23163190
TI  - Influenza in the Pacific.
AB  - Influenza A and B viruses cause significant human disease worldwide through
      regular outbreaks and epidemics of seasonal influenza, and occasional pandemics
      when a novel influenza A virus emerges. Whereas Australia and New Zealand have
      well-established systems for community and laboratory-based surveillance of
      influenza, most other countries of the Pacific are only beginning to develop such
      systems with the support of various global and regional agencies and networks.
      Here we describe the role of the World Health Organization Global Influenza
      Surveillance Network and other organizations in laboratory-based influenza
      surveillance in the region and review some of the available data on seasonal and
      pandemic influenza in the developed and developing countries of the Pacific. The
      particular features of the Pacific Island countries and territories as small
      dispersed island communities, together with the greater susceptibility of
      indigenous people to the severe effects of influenza, highlight the importance of
      developing local laboratory-based surveillance systems. Such systems will improve
      the understanding, detection and control of seasonal influenza while also
      providing early warning of the emergence of potential pandemic viruses.

PMID- 23163192
TI  - Residential therapy. Hospitals take on finding housing for homeless patients,
      hoping to reduce readmissions, lower costs.
AB  - As they grapple with containing the cost of caring for patients who frequently
      return to the ER or hospital for care, some hospitals are trying a new route:
      housing. In San Francisco, plans are under way to house 50 homeless patients.
      "Hospitalization is a failure of the medical system. It means that the condition
      has gotten so out of control that someone is at risk of life or limb," says Dr.
      Kelly Pfeifer, left, of the San Francisco Health Plan.

PMID- 23163193
TI  - 'Devastating impact'. Budget cuts could stymie user-fee deals, cost jobs.

PMID- 23163191
TI  - A neonatal pneumococcal conjugate vaccine trial in Papua New guinea: study
      population, methods and operational challenges.
AB  - Infants in Papua New Guinea (PNG) are at a high risk of invasive pneumococcal
      disease, and a substantial burden of this falls on children less than six months
      old. PNG is planning to introduce a pneumococcal conjugate vaccine for infants in
      the near future, but to make the maximum impact neonatal immunization will have
      to be considered. To provide evidence on safety and immunogenicity for neonatal
      and early infant immunization, we undertook an open randomized controlled trial
      of 7-valent pneumococcal conjugate vaccine (7vPCV). 318 children received 7vPCV
      at ages 0, 1 and 2 months or at 1, 2 and 3 months or not at all. All children
      received 23-valent pneumococcal polysaccharide vaccine at age 9 months. This was
      a large and complex trial: village reporters visited participants weekly during
      the first year and fortnightly for a further 6 months and nurses monitored self
      reported morbidity and collected many thousands of biological samples. The study
      team was remarkably successful in achieving the study aims, with 18-month follow
      up completed on 77% of enrolled children and over 80% of scheduled samples
      collected. While the results of the trial will be reported elsewhere, this paper
      discusses the design of the study and dissects out some of the main reasons for
      its successful completion. Strong community engagement was an essential factor in
      success and the principles of equitable partnership and service provision led to
      a strong research partnership. A two-stage consent process, comprising primary
      assent followed by later informed consent, led to a high drop-out before initial
      enrolment, but an outstanding retention of those enrolled in the study. We
      conclude that factors such as strong community participation, reciprocity and a
      good relationship between the study team and participants are just as important
      as the technical elements of laboratory testing and data handling in ensuring the
      success of a vaccine trial in PNG.

PMID- 23163194
TI  - LifeCare's debt bomb. Sale, restructuring possible as LTAC pressures mount.

PMID- 23163195
TI  - Working with the rules. Data tagging allows selective sharing with EHRs.

PMID- 23163196
TI  - Systems align in Mass.

PMID- 23163197
TI  - Reconsider doc-ownership clause. ACA provision could lead to higher service
      costs, hinder reform's goals.

PMID- 23163198
TI  - Nourishing change. Partnership enlists dozens of hospitals to put healthier food
      on their menus and kick junk food out of the cafeteria.
AB  - More than 150 hospitals have signed on to the Partnership for a Healthier
      America's push to ditch the deep-fat fryer in their cafeterias and bulk up on
      fruit and veggies. "Our focus is to ensure that if people want to make a healthy
      choice, they can," says Larry Soler, left, president and CEO of the partnership,
      which is working to reduce childhood obesity.

PMID- 23163199
TI  - CMS errs on penalties. 1,422 hospitals will lose more under revised policy.

PMID- 23163200
TI  - Fighting for funds. Pressure persists to find donors, despite record year.

PMID- 23163201
TI  - Flirting with taxable markets. Dignity Health seeks to refinance acquisition
      debt.

PMID- 23163202
TI  - Highmark not letting go. Files suit to stop West Penn from pursuing new deal.

PMID- 23163203
TI  - Riding the 'roller coaster'. ICD-10, pirates and privacy are hot topics at annual
      IT gathering.

PMID- 23163204
TI  - Planning ahead. Tenet to put $400 million toward deals.

PMID- 23163205
TI  - Sore subject. Nurses react as AAFP report backs doctor-led medical homes.

PMID- 23163206
TI  - Check, please. Bill me now for services rendered so I can avoid payment hassles
      later.

PMID- 23163207
TI  - Q fever at the turn of the century.
AB  - Q fever is an infectious zoonotic disease characterized by sudden fever,
      headache, and atypical pneumonia, caused by Coxiella burneti--an obligatory
      intracellular parasite. Based on phylogenetic analysis of the genes sequences,
      the classification was changed and C. burnetii species was included to the gamma
      subgroup of the proteobacteria, Legionellales order and Coxiellaceae family. This
      analysis showed more than 99% sequence similarity of 16SrRNA gene among the
      strains isolated in different regions of the world. Q fever is a widespread in
      the world zoonosis. Its main reservoir in the rural environment are farm animals:
      cows, sheep, goats, and urban pets such as dogs, cats, rabbits. In acute
      infection these bacteria are detected in various internal organs such as lungs,
      liver, spleen, and in excretion in urine, faeces and milk. During childbirth,
      they occur in large number in the amniotic fluid and placenta. Recently, it has
      been found that free-living amoeba Acanthamoeba castellani may also be a
      reservoir of the pathogen. The intra-amoebal location of C. burnetii cells was
      observed.

PMID- 23163208
TI  - Synergy between novel antimicrobials and conventional antibiotics or
      bacteriocins.
AB  - Due to the alarming spread of resistance to classic antimicrobial agents,
      innovative therapeutic methods to combat antibiotic-resistant bacterial pathogens
      are urgently required. This minireview examines the enhancement of antibiotic
      efficacy by their combination with new antimicrobials, such as plant-derived
      compounds, metal ions and nanoparticles and bacteriophage lytic enzymes. The
      mechanisms of the observed synergy are also described. The promising results of
      basic research indicate that in future, combined therapy may be applied in human
      and veterinary medicine, agriculture and the food industry to combat bacterial
      pathogens.

PMID- 23163209
TI  - Virulence genes profiles and phylogenetic origin of Escherichia coli from acute
      and chronic intestinal diseases revealed by comparative genomic hybridization
      microarray.
AB  - The association between Escherichia coli virulence factors and chronic intestinal
      disorders is mostly unknown. The presented study compared the distribution of
      virulence genes and phylogroups among E. coli isolated from chronic intestinal
      disorders such as Crohn's disease and irritable bowel syndrome (IBS) with strains
      isolated from patients with acute diarrhea as a control group. The presence of
      159 virulence genes corresponding to known E. coli pathotypes was determined
      among 78 E. coli archive strains isolated from IBS, acute diarrhea and Crohn's
      disease using CGH microarray. E. coli isolated from IBS demonstrated a mosaic of
      virulence genes specific to enteropathogenic, enterotoxigenic, enterohemorrhagic
      E. coli strains and Shigella species. In contrast, virulence factors and
      phylogroups distribution among E. coli isolated from children with acute diarrhea
      was similar to extraintestinal E. coli strains that probably acquired some
      virulence genes. The acquisition of virulence genes might have an impact on
      diarrheagenic potential of these strains. On the other hand, E. coli isolated
      from children with Crohn's disease seem to be similar to adherent-invasive E.
      coli strains (AIEC), as it lack most known virulence genes. The presented study
      showed that these analyzed groups of E. coli strains differed from each other
      with the respect to the distribution of virulence genes. The differences in gene
      content support the idea that the participation of E. coli in chronic intestinal
      diseases is mostly related to virulence potential of these strains.

PMID- 23163210
TI  - Isolation, characterization and phylogenetic analysis of halophilic archaea from
      a salt mine in central Anatolia (Turkey).
AB  - The haloarchaeal diversity of a salt mine, a natural cave in central Anatolia,
      was investigated using convential microbiological and molecular biology methods.
      Eight halophilic archaeal isolates selected based on their colony morphology and
      whole cell protein profiles were taxonomically classified on the basis of their
      morphological, physiological, biochemical properties, polar lipid and protein
      profiles and 16S rDNA sequences. From the 16S rDNA sequences comparisons it was
      established that the isolates CH2, CH3 and CHC resembled Halorubrum saccharovorum
      by 98.8%, 98.9% and 99.5%, respectively. There was a 99.7% similarity between the
      isolate CH11 and Halobacterium noricense and 99.2% between the isolate CHA1 and
      Haloarcula argentinensis. The isolate CH8K and CH8B revealed a similarity rate of
      99.8% and 99.3% to Halococcus dombrowskii, respectively. It was concluded that
      the isolates named CH2, CH3 and CHC were clustered in the genus Halorubrum and
      that CHA1 and CH7 in the genus Haloarcula, CH8K and CH8B in the genus Halococcus
      and CH11 in the genus Halobacterium.

PMID- 23163211
TI  - Antagonistic effects of Bacillus cereus strain B-02 on morphology, ultrastructure
      and cytophysiology of Botrytis cinerea.
AB  - The study on antagonistic mechanism of biocontrol strains gives the premise and
      basis for efficient and stable biological control. This study aimes to overcome
      of biocontrol agent in aspects of complicated and diversified mode of action,
      short-lasting and unstable efficacy in the production processes. This study
      elucidated the antagonistic mechanism of Bacillus cereus strain B-02 on Botrytis
      cinerea by detecting changes in morphology, ultrastructure and physiology in
      affected hyphae of Botrytis cinerea. Which provided certain theoretical and
      practical significance for biological control of gray mould caused by B. cinerea.
      B. cereus strain B-02 isolated from tomato rhizosphere mightily suppressed gray
      mold in tomato caused by B. cinerea. Spore germination and hyphal growth of B.
      cinerea were inhibited by B. cereus strain B-02. Changes of cell morphology such
      as distortion, shrinking and swelling were observed by SEM. TEM observation
      further indicated the ultrastructural alterations of hyphae, including
      mitochondrion reduction, un-membranous inclusion in cytoplasm, considerable
      thickening of cell walls, and electronic density enhancement. LSCM observation
      revealed the fluorescence intensity of nucleus DNA, mitochondrion DNA and
      reactive oxygen radical in treated hyphae were all stronger than control and the
      difference was significant (P < 0.01). These results indicated that the
      antagonistic effects of B. cereus strain B-02 on B. cinerea were likely due to a
      combination of abnormal synthesis of nucleus DNA and mitochondrion DNA and
      multifarious ultrastructural alterations in hyphal cell.

PMID- 23163212
TI  - Ultrastructure of Candida albicans pleomorphic forms: phase-contrast microscopy,
      scanning and transmission electron microscopy.
AB  - A modified method of glutaraldeyde-osmium tetroxide fixation was adjusted to
      characterize the ultrastructure of Candida albicans pleomorphic forms, using
      phase-contrast microscopy, scanning electron microscopy and transmission electron
      microscopy. The discovered morphological criteria defining the individual
      morphotypes are discussed in terms of mycological and histopathological
      diagnostics of candidiasis. The relations are discussed between fungal
      pleomorphism, virulence and susceptibility of different morphotypes to
      fungicides.

PMID- 23163213
TI  - Modifications influencing Widal test reactivity in a novel microplate assay.
AB  - Reliability of the Widal tube agglutination test has been the subject of many
      controversies over the years. This study was performed to assess the effect of
      certain modifications on the performance of Widal test in a novel microplate
      assay. Sera from 37 patients (21 males; 16 females) (mean age 28 +/- 7 years)
      were tested in the Immunology Unit at King Khalid University Hospital, Riyadh.
      Among them were 26 patients with suspected typhoid fever and 11 had
      bacteriologically confirmed diagnosis of Salmonella infection. The modifications
      included either the use of 0.5% bovine serum albumin (BSA), absorption of sera
      with sheep red blood cells (SRBC) or heat inactivation of sera. Compared with
      Widal tube agglutination test, microplate assay with SRBC absorption of the sera
      from patients with suspected typhoid fever was not only associated with
      enhancement of detection titers for both H (p < or = 0.001) and O (p < or =
      0.005) Salmonella agglutinins but also the percentage of reactivity. The presence
      of BSA augmented detection titers for Salmonella H agglutinins (p < or = 0.02)
      only. Heat inactivation of sera however was found to be associated with reduction
      in the detectable titers for both H (p < or = 0.03) and O (p < or = 0.01)
      agglutinins. Increased titers of Salmonella agglutinins were also evident in 11
      patients with confirmed diagnosis of Salmonella infection. The novel microplate
      agglutination assay using the SRBC absorption was associated with enhancement in
      Widal test reactivity and appears to be a useful alternative for the diagnosis of
      Salmonella infection.

PMID- 23163214
TI  - Susceptibility of Polish Bartonella henselae strains.
AB  - Due to the fastidious nature of B. henselae and the limited number of available
      isolates worldwide, there are few data on its in vitro susceptibility to
      antibiotics. We determined the minimal inhibitory concentrations (MIC) of ten
      antimicrobial agents against 11 feline isolates of B. henselae by Etest method.
      The lowest MICs were obtained for rifampicin < or = 0.002 mg/L. MICs of all
      isolates were < 0.016 mg/L for ampicilin, amoxicillin/clavulanic acid,
      tetracycline and ranged from 0.016 to 0.032 mg/L for azithromycin. The MICs for
      two tested fluoroquinolones: ciprofloxacin and levofloxacin ranged from 0.016 to
      0.125 mg/L. The highest MICs were obtained for gentamicin ranging from 0.025 to
      2.0 mg/L. Sulphonamide resistance genes sul 1, sul 2, sul 3 were not found in any
      of the tested isolates. Etest methodology seems to be a reliable method for
      determination of B. henselae susceptibility, however standardization is strongly
      desired.

PMID- 23163215
TI  - The relationship between H. pylori virulence genotypes and gastric diseases.
AB  - There have been no reports on the relationship between virulence genes and
      gastric diseases based on the same bacterial colonization density. Our results
      indicated that Helicobacter pylori virulence genes were more relevant than
      colonization density as a pathogenic mechanism of gastric diseases, which helps
      elucidate the pathogenic mechanisms of bacteria and aids in the development of
      improved strategies for the treatment of gastric disease.

PMID- 23163216
TI  - Preparing for impact. Many hospitals will struggle to escape or absorb penalty
      for readmissions.
AB  - October brings the beginning of a program hospitals around the country have been
      anxiously awaiting--a program that will penalize them for too-high readmission
      rates. Many fear the economics of the program will drive independent, community
      hospitals to join systems. "We are the hospitals that are least able to effect
      change, and we're being asked to do the most," says Stephen Estes, of Rockcastle
      Regional Hospital and Respiratory Care Center.

PMID- 23163217
TI  - Warning bell. Potential for fraud through use of EHRs draws federal scrutiny.

PMID- 23163218
TI  - Against the rules. Proposed not-for-profit regulations draw complaints.

PMID- 23163219
TI  - Holding them accountable. HHS targets former officials for company's alleged role
      in patients' deaths.

PMID- 23163220
TI  - A call for collaboration. FCC urged to stay the course on mobile health effort.

PMID- 23163221
TI  - New deal. After Landmark loses Steward deal, Prime steps in.

PMID- 23163222
TI  - It's debatable. Will Obama and Romney take advantage of faceoff to detail policy
      positions?

PMID- 23163223
TI  - Aiming for coding accuracy. Data governance is becoming critical factor in EHR
      implementation.

PMID- 23163224
TI  - Into the breach. The number of medical records being stolen and hacked continues
      to rise, along with the illegal activity resulting from use of the data.

PMID- 23163225
TI  - Covered at no cost. Some employers still pay the full health premium.

PMID- 23163226
TI  - Thiolate-protected nanoparticles via organic xanthates: mechanism and
      implications.
AB  - The gold nanoparticles (AuNPs) stabilized with amine ligands are converted into
      robust thiolate-protected AuNPs in the presence of xanthates. This enables
      decoration of the AuNPs with a diversity of important functional groups, in
      particular, to introduce the thiol-sensitive unsaturated C-C bonds. The (1)H NMR
      study on the reaction mechanism provides a new insight into the great mystery of
      nanoscience-the fate of hydrogen upon the formation of the Au-S bond.

PMID- 23163228
TI  - Net degradation of methyl mercury in alder swamps.
AB  - Wetlands are generally considered to be sources of methyl mercury (MeHg) in
      northern temperate landscapes. However, a recent input-output mass balance study
      during 2007-2010 revealed a black alder (Alnus glutinosa) swamp in southern
      Sweden to be a consistent and significant MeHg sink, with a 30-60% loss of MeHg.
      The soil pool of MeHg varied substantially between years, but it always decreased
      with distance from the stream inlet to the swamp. The soil MeHg pool was
      significantly lower in the downstream as compared to the upstream half of the
      swamp (0.66 and 1.34 ng MeHg g-1 SOC-1 annual average-1, respectively, one-way
      ANOVA, p = 0.0006). In 2008 a significant decrease of %MeHg in soil was
      paralleled by a significant increase in potential demethylation rate constant
      (k(d), p < 0.02 and p < 0.004, respectively). In contrast, the potential
      methylation rate constant (k(m)) was unrelated to distance (p = 0.3). Our results
      suggest that MeHg was net degraded in the Alnus swamp, and that it had a rapid
      and dynamic internal turnover of MeHg. Snapshot stream input-output measurements
      at eight additional Alnus glutinosa swamps in southern Sweden indicate that Alnus
      swamps in general are sinks for MeHg. Our findings have implications for forestry
      practices and landscape planning, and suggest that restored or preserved Alnus
      swamps may be used to mitigate MeHg produced in northern temperate landscapes.

PMID- 23163229
TI  - Dissecting molecular interactions involved in recognition of target disulfides by
      the barley thioredoxin system.
AB  - Thioredoxin reduces disulfide bonds, thus regulating activities of target
      proteins in various biological systems, e.g., inactivation of inhibitors of
      starch hydrolases and proteases in germinating plant seeds. In the three
      dimensional structure of a complex with barley alpha-amylase/subtilisin inhibitor
      (BASI), two loops in barley thioredoxin h2 (HvTrxh2), containing an invariant cis
      proline ((86)EAMP(89)) and a conserved glycine ((104)VGA(106)), surround the
      active site cysteines ((45)WCGPC(49)) and contribute to binding of BASI through
      backbone-backbone hydrogen bonds [Maeda, K., Hagglund, P., Finnie, C., Svensson,
      B., and Henriksen, A. (2006) Structure 14, 1701-1710]. This study involves
      mutational analysis of key amino acid residues from these two loops in reactions
      with three protein disulfide substrates, BASI, barley glutathione peroxidase, and
      bovine insulin as well as with NADPH-dependent barley thioredoxin reductase.
      HvTrxh2 M88G and M88A adjacent to the invariant cis-proline lost efficiency in
      both BASI disulfide reduction and recycling by thioredoxin reductase. These
      effects were further pronounced in M88P lacking a backbone NH group. Remarkably,
      HvTrxh2 E86R in the same loop displayed overall retained catalytic properties,
      with the exception of a 3-fold increased activity toward BASI. From the
      (104)VGA(106) loop, a backbone hydrogen bond donated by A106 appears to be
      important for target disulfide recognition as A106P lost 90% activity toward BASI
      but was efficiently recycled by thioredoxin reductase. The findings support
      important roles in target recognition of backbone-backbone hydrogen bond and
      electrostatic interactions and are discussed in relation to earlier structural
      and functional studies of thioredoxins and related proteins.

PMID- 23163231
TI  - Outcome after placement of an artificial urethral sphincter in 27 dogs.
AB  - OBJECTIVE: To evaluate the safety and efficacy of an adjustable artificial
      urethral sphincter (AUS) in a population of dogs with acquired or congenital
      urinary incontinence. STUDY DESIGN: Case series. ANIMALS: Dogs (n = 27) with
      naturally occurring urinary incontinence. METHODS: Medical records (January 2009
      July 2011) of dogs that had AUS implantation for treatment of urinary
      incontinence were reviewed and owners were interviewed by telephone to assess
      outcome. Continence was scored using a previously established analogue scale,
      with 1 representing constant leakage and 10 representing complete continence.
      RESULTS: Twenty-four female and 3 male dogs had AUS implantation. Causes of
      incontinence included urethral sphincter mechanism incompetence (n = 18),
      continued incontinence after ectopic ureter repair (6), and pelvic bladder (3).
      Medical therapy was unsuccessful in 25 dogs before AUS implantation. Surgery was
      performed without major complications in 25 dogs; 2 developed partial urethral
      obstruction after 5 and 9 months. Median (interquartile range) follow-up for the
      other 25 dogs was 12.5 (6-19) months. Continence scores were significantly
      improved (P < .0001) between the preoperative period (2 [1-4]) and last follow-up
      (9 [8-10]). Overall, 22 owners described themselves as very satisfied, 2 as
      satisfied, and 3 as unsatisfied. CONCLUSIONS: AUS implantation was successful in
      restoring continence in male and female dogs with both congenital and acquired
      urinary incontinence. Dogs that develop partial urethral obstruction may require
      AUS removal.

PMID- 23163230
TI  - Conjugates of superoxide dismutase 1 with amphiphilic poly(2-oxazoline) block
      copolymers for enhanced brain delivery: synthesis, characterization and
      evaluation in vitro and in vivo.
AB  - Superoxide dismutase 1 (SOD1) efficiently catalyzes dismutation of superoxide,
      but its poor delivery to the target sites in the body, such as brain, hinders its
      use as a therapeutic agent for superoxide-associated disorders. Here to enhance
      the delivery of SOD1 across the blood-brain barrier (BBB) and in neurons the
      enzyme was conjugated with poly(2-oxazoline) (POx) block copolymers, P(MeOx-b
      BuOx) or P(EtOx-b-BuOx), composed of (1) hydrophilic 2-methyl-2-oxazoline (MeOx)
      or 2-ethyl-2-oxazoline (EtOx) and (2) hydrophobic 2-butyl-2-oxazoline (BuOx)
      repeating units. The conjugates contained from 2 to 3 POx chains joining the
      protein amino groups via cleavable -(ss)- or noncleavable -(cc)- linkers at the
      BuOx block terminus. They retained 30% to 50% of initial SOD1 activity, were
      conformationally and thermally stable, and assembled in 8 or 20 nm aggregates in
      aqueous solution. They had little if any toxicity to CATH.a neurons and displayed
      enhanced uptake in these neurons as compared to native or PEGylated SOD1. Of the
      two conjugates, SOD1-(cc)-P(MeOx-b-BuOx) and SOD1-(cc)-P(EtOx-b-BuOx), compared,
      the latter was entering cells 4 to 7 times faster and at 6 h colocalized
      predominantly with endoplasmic reticulum (41 +/- 3%) and mitochondria (21 +/-
      2%). Colocalization with endocytosis markers and pathway inhibition assays
      suggested that it was internalized through lipid raft/caveolae, also employed by
      the P(EtOx-b-BuOx) copolymer. The SOD activity in cell lysates and ability to
      attenuate angiotensin II (Ang II)-induced superoxide in live cells were increased
      for this conjugate compared to SOD1 and PEG-SOD1. Studies in mice showed that
      SOD1-POx had ca. 1.75 times longer half-life in blood than native SOD1 (28.4 vs
      15.9 min) and after iv administration penetrated the BBB significantly faster
      than albumin to accumulate in brain parenchyma. The conjugate maintained high
      stability both in serum and in brain (77% vs 84% at 1 h postinjection). Its
      amount taken up by the brain reached a maximum value of 0.08% ID/g (percent of
      the injected dose taken up per gram of brain) 4 h postinjection. The entry of
      SOD1-(cc)-P(EtOx-b-BuOx) to the brain was mediated by a nonsaturable mechanism.
      Altogether, SOD1-POx conjugates are promising candidates as macromolecular
      antioxidant therapies for superoxide-associated diseases such as Ang II-induced
      neurocardiovascular diseases.

PMID- 23163232
TI  - Riboswitch-based antibacterial drug discovery using high-throughput screening
      methods.
AB  - INTRODUCTION: Bacterial riboswitches are structured RNA domains usually residing
      at the 5' untranslated region of messenger RNAs that can directly bind specific
      metabolites. They serve as logic gates regulating gene expression. As a result,
      riboswitches enable mRNAs to regulate their own expression without the need for
      any regulatory proteins. The first riboswitches were found just 10 years ago.
      Over the last decade, more than dozen different riboswitch classes were
      identified in many bacterial species, and their number is still growing. These
      findings indicate that bacteria widely use RNA switches to sense changes in cell
      physiology and to regulate metabolic pathways. AREAS COVERED: The authors discuss
      the main mechanisms for riboswitch control of gene expression in bacteria.
      Various riboswitch classes were found in human bacterial pathogens to control the
      synthesis of essential cell metabolites as discussed in this review. Some
      riboswitches can be used as novel targets for antibacterial drug discovery. This
      review presents the current and possible future high-throughput screening
      approaches for targeting riboswitches in the process of drug development. EXPERT
      OPINION: Bacterial riboswitches of 17 different classes are discovered in 36
      human bacterial pathogens that can be targeted for addressing the ever-growing
      need for new antibiotics. In this regard, the adaptation of various in silico, in
      vitro, and in vivo high-throughput screening methods for probing specific RNA
      switches are crucial for the success of antibacterial drug discovery process.

PMID- 23163233
TI  - Short- and long-term outcome after perineal urethrostomy in 86 cats with feline
      lower urinary tract disease.
AB  - BACKGROUND: Perineal urethrostomy is a surgical method for alleviating urethral
      obstruction in cats with complicated or recurrent obstructive feline lower
      urinary tract disease. However, long-term outcome of perineal urethrostomy in
      cats with feline lower urinary tract disease has only been described in studies
      with relatively few cats. OBJECTIVES: The aim of this study was to evaluate the
      long-term prognosis, recurrent episodes, quality of life and survival times in
      cats with feline lower urinary tract disease who underwent perineal urethrostomy.
      MATERIALS AND METHODS: Data was collected from 86 cats from medical records,
      including 75 cats with at least 6 months survival, whose owners responded by
      questionnaire-based telephone interviews. RESULTS: Long-term follow-up ranged
      from 1.0 to 10.4 years. The median survival time for all cats was 3.5 years after
      surgery. Forty-seven cats were still alive at the time of the study. Five cats
      (5.8%) did not survive the first 14 days after perineal urethrostomy surgery;
      another six cats (7.0%) did not survive 6 months. Seventy-five cats (87%) lived
      longer than 6 months; 45 (60%) of these were asymptomatic after surgery; 8 of 75
      cats (10.7%) experienced severe signs of recurrent feline lower urinary tract
      disease. For 19 cats, data were available for more than 6 years. Among these, 13
      cats were still alive at the time of this study. The six non-surviving cats had
      all been euthanased for diseases unrelated to the urinary tract. Eighty-eight
      percent of the owners categorised their cat's long-term quality of life as good.
      CLINICAL SIGNIFICANCE: This study shows that long-term quality of life after
      perineal urethrostomy in cats with obstructive feline lower urinary tract disease
      is good (as assessed by owners) and the recurrence rate is low.

PMID- 23163234
TI  - A multi-state assessment of employer-sponsored quality improvement education for
      early-career registered nurses.
AB  - BACKGROUND: Increasing participation of registered nurses (RNs) in quality
      improvement (QI) is a promising strategy to close the health care quality chasm.
      For RNs to participate effectively in hospital QI, they must have adequate QI
      knowledge and skills. METHODS: This descriptive study assessed employer-sponsored
      QI education and RNs' preparedness across a wide range of QI steps and processes.
      RNs from 15 U.S. states who were employed in hospitals and were initially
      licensed to practice in 2007 to 2008 were surveyed. RESULTS: Fewer than one third
      of respondents reported being very prepared across all measured QI topics. More
      than half reported receiving zero hours of training in these same topics in the
      last year. Lack of educational offerings on the topic was the top reason
      respondents gave for not obtaining QI training. CONCLUSION: The QI education
      offered by employers to RNs could be substantially improved. Nurse educators play
      a critical role in making these improvements.

PMID- 23163236
TI  - Autism and other psychiatric comorbidity in neurofibromatosis type 1: evidence
      from a population-based study.
AB  - AIM: To investigate psychopathology in children with neurofibromatosis type 1
      (NF1), particularly the prevalence of autism spectrum disorder (ASD) and
      attention-deficit-hyperactivity disorder (ADHD) symptomatology, using a
      population-based sampling approach. METHOD: Standard questionnaire screen reports
      were analysed for ASD (Social Responsiveness Scale, SRS), ADHD (Conners' Parent
      Rating Scale- Revised, CPRS-R), and other psychiatric morbidity (Strengths and
      Difficulties Questionnaire, SDQ) from parents and teachers of children aged from
      4 to 16 years (112 females, 95 males) on the UK North West Regional Genetic
      Service register for NF1. RESULTS: Parental response rate was 52.7% (109/207
      children; 59 females, 50 males, mean age 9 y 11 mo, SD 3 y 3 mo). The SRS showed
      that in 29.4% (32/109) of children, autism was in the severe, clinical range (T
      score>75) and in 26.6% (29/109) in the mild to moderate range (T-score 60-75).
      CPRS-R scores showed that in 53.8% (57/106) of children autism was in the
      clinical ADHD range (ADHD index T-score>65). Based on their scores on the SDQ
      total difficulties scale, 41.5% (44/106) of children were in the abnormal range
      and 14.2% (15/106) were in the borderline range. Twenty-five per cent (26/104) of
      children met criteria for both clinical autism and ADHD. INTERPRETATION: This
      representative population-based sample of children with NF1 indicates a high
      prevalence of ASD symptoms associated with NF1 as well as substantial co
      occurrence with ADHD symptoms. The findings clarify the psychopathology of NF1
      and show the disorder as a potentially important single-gene cause for autism
      symptoms.

PMID- 23163235
TI  - The relationship between cerebral amyloid angiopathy and cortical microinfarcts
      in brain ageing and Alzheimer's disease.
AB  - AIMS: Cerebral amyloid angiopathy (CAA) represents the deposition of amyloid beta
      protein (Abeta) in the meningeal and intracerebral vessels. It is often observed
      as an accompanying lesion of Alzheimer's disease (AD) or in the brain of elderly
      individuals even in the absence of dementia. CAA is largely age-dependent. In
      subjects with severe CAA a higher frequency of vascular lesions has been
      reported. The goal of our study was to define the frequency and distribution of
      CAA in a 1-year autopsy population (91 cases) from the Department of Internal
      Medicine, Rehabilitation, and Geriatrics, Geneva. MATERIALS AND METHODS: Five
      brain regions were examined, including the hippocampus, and the inferior
      temporal, frontal, parietal and occipital cortex, using an antibody against
      Abeta, and simultaneously assessing the severity of AD-type pathology with Braak
      stages for neurofibrillary tangles identified with an anti-tau antibody. In
      parallel, the relationships of CAA with vascular brain lesions were established.
      RESULTS: CAA was present in 53.8% of the studied population, even in cases
      without AD (50.6%). The strongest correlation was seen between CAA and age,
      followed by the severity of amyloid plaques deposition. Microinfarcts were more
      frequent in cases with CAA; however, our results did not confirm a correlation
      between these parameters. CONCLUSION: The present data show that CAA plays a role
      in the development of microvascular lesions in the ageing brain, but cannot be
      considered as the most important factor in this vascular pathology, suggesting
      that other mechanisms also contribute importantly to the pathogenesis of
      microvascular changes.

PMID- 23163237
TI  - Phellinus baumii extract influences pathogenesis of Brucella abortus in phagocyte
      by disrupting the phagocytic and intracellular trafficking pathway.
AB  - AIMS: To clarify the effects of Phellinus baumii ethanol extract (PBE) on
      Brucella abortus pathogenesis in phagocytes focusing on the phagocytic and
      intracellular trafficking pathway. METHODS AND RESULTS: The effects of PBE on Br.
      abortus infection in macrophages were evaluated through an adherence and
      infection assays and an analysis of LAMP-1 staining. The phosphorylation of
      ERK1/2 and the F-actin polymerization associated with PBE during Br. abortus
      uptake were detected by immunoblotting and FACS, respectively. The survival of
      Br. abortus in pure culture was remarkably reduced by PBE in a dose-dependent
      manner. PBE-treated cells showed significantly decreased uptake, intracellular
      replication and adherence of Br. abortus. The declines of ERK1/2 phosphorylation
      and F-actin polymerization following Br. abortus entry were apparent in PBE
      treated cells compared with the control. Moreover, the co-localization of Br.
      abortus-containing phagosomes with LAMP-1 was elevated in PBE-treated cells
      compared with the control during intracellular trafficking. CONCLUSION: Phellinus
      baumii ethanol extract may possess the modulatory effect on pathogenesis of Br.
      abortus through disrupting the phagocytic and intracellular trafficking pathway
      in phagocyte. SIGNIFICANCE AND IMPACT OF THE STUDY: The potential modulation of
      PBE to Br. abortus pathogenesis could provide an alternative approach to control
      of brucellosis, contributing to attenuate Br. abortus manifestation in hosts.

PMID- 23163238
TI  - Isolation and biomimetic synthesis of (+/-)-guajadial B, a novel meroterpenoid
      from Psidium guajava.
AB  - (+/-)-Guajadial B (1), an unusual humulene-based meroterpenoid, was isolated as a
      racemate from the leaves of Psidium guajava, collected from Vietnam. The
      structure of this novel secondary metabolite was established on the basis of
      extensive analysis of NMR spectra and confirmed by biomimetic synthesis in a
      domino three-component coupling reaction.

PMID- 23163239
TI  - Predicting exercise adherence in cancer patients and survivors: a systematic
      review and meta-analysis of motivational and behavioural factors.
AB  - AIMS AND OBJECTIVES: To examine research findings regarding predictors of
      adherence to exercise programmes in cancer populations. BACKGROUND: Cancer
      patients are advised to participate in daily exercise. Whether they comply with
      the recommendations for physical activity or not remains unclear. DESIGN: A
      systematic review and meta-analysis. METHODS: Empirical articles published in
      English between 1995 and 2011 were searched in electronic databases and in
      reference lists, using the search terms 'adherence', 'predictors', 'exercise',
      and 'cancer' in varying combinations. Twelve of 541 screened abstracts met the
      inclusion criteria. The included studies' eligibility considering predictors of
      exercise adherence were reviewed. A quality assessment process evaluating the
      studies methodological quality was performed. Eight of the reviewed studies were
      considered eligible for a meta-analysis involving Pearson's r correlations.
      RESULTS: Exercise stage of change, derived from the transtheoretical model of
      behaviour change (TTM) was found to be statistically significant and a strong
      predictor of exercise adherence. In addition, the theory of planned behaviour
      (TPB) construct; intention to engage in a health-changing behaviour and perceived
      behavioural control, demonstrated significant correlations with exercise
      adherence. CONCLUSIONS: The review identified that both the TPB and the TTM
      frameworks include aspects that predicts exercise adherence in cancer patients,
      and thus contributes to the understanding of motivational factors of change in
      exercise behaviour in cancer populations. However, the strengths of predictions
      were relatively weak. More research is needed to identify predictors of greater
      importance. RELEVANCE TO CLINICAL PRACTICE: Surveying the patients' readiness and
      intention to initiate and maintain exercise levels, as well as tailoring exercise
      programmes to individual needs may be important for nurses in order to help
      patients meet exercise guidelines and stay active.

PMID- 23163240
TI  - Mortality among older adults after a traumatic brain injury: a meta-analysis.
AB  - PRIMARY OBJECTIVE: To examine mortality rates among older adults (>=60 years)
      post-traumatic brain injury (TBI). RESEARCH DESIGN: Systematic review and meta
      analysis. METHODS AND PROCEDURES: Using multiple databases, a literature search
      was conducted for articles on mortality after TBI published up to July 2011.
      Information on patient characteristics (age, Glasgow Coma Scale (GCS), injury
      aetiology, etc.), mortality rates, time to death and study design was extracted
      and pooled. MAIN OUTCOMES AND RESULTS: Twenty-four studies had an overall
      mortality rate of 38.3% (CI 27.1-50.9%). The odds of mortality for those over 75
      years compared to those of 65-74 years was 1.734 (CI = 1.311-2.292; p < 0.0001).
      Pooled mortality rates for mild (GCS 13-15), moderate (GCS 9-12) and severe (GCS
      3-8) head injuries were 12.3% (CI = 6.1-23.3%), 34.3% (CI = 19.5-53.0%) and 65.3%
      (CI = 53.1-75.9), respectively. Odds ratios comparing severe to mild and moderate
      to mild head injuries were 12.69 (CI = 5.29-30.45; p < 0.0001) and 5.31 (CI =
      3.41-8.29; p < 0.0001), respectively. There was no significant difference in the
      odds of death between severe and moderate injuries (p = 0.116). CONCLUSIONS:
      These mortality rates associated with moderate and severe injuries may be
      attributed to complications, chronic disease prevalence, conservative management
      techniques or the consequences of biological ageing.

PMID- 23163241
TI  - Seat belt utilisation and awareness in UAE.
AB  - Seat belts (SBs) are effective devices for reducing injury risk due to traffic
      accidents. Seat belt wearing was made compulsory in the United Arab Emirates
      (UAE) in January 1999 for drivers and front seat passengers (FSPs). No
      comprehensive study has ever assessed SB wearing rates across the country. Also,
      little is known on drivers' awareness of the importance of wearing seatbelts and
      how human factors affect wearing habits. This study aims to determine SB wearing
      rates for drivers and FSPs in UAE through an observational field study. It also
      aims to investigate perceptions and behaviour of drivers on this issue as well as
      human factors that affect wearing rate through a randomly distributed
      questionnaire. The results of the field study show that the overall SB wearing
      rate across the country was 61% for drivers and 43.4% for FSPs and that there
      were significant differences between the seven emirates that constitute the
      country. The questionnaire results show that age, education level, gender,
      marital status and nationality of drivers affect wearing habits and perceptions.
      Future implications in terms of improving traffic safety awareness are discussed.

PMID- 23163242
TI  - NMDA receptors in the midbrain play a critical role in dopamine-mediated
      hippocampal synaptic potentiation caused by morphine.
AB  - A single exposure to drugs of abuse produces an NMDAR (N-methyl-D-aspartate
      receptor)-dependent synaptic potentiation at excitatory synapses of dopamine (DA)
      neurons in the ventral tegmental area (VTA) of the midbrain. All addictive drugs
      can increase DA concentrations in projection areas of the midbrain, including the
      hippocampus. Hippocampal DA release subsequently modulates hippocampal plasticity
      and drug-associated memories. Using in vivo electrophysiological recording
      techniques in anesthetized rats, we show that systemic injection of morphine
      induced hippocampal synaptic potentiation in a dose-dependent manner. Intra-VTA
      but not intra-hippocampus injection of morphine evoked this potentiation. Local
      hippocampal dopamine D1 receptors (D1R) are required in the morphine-induced
      synaptic potentiation and conditioned place preference (CPP). Moreover, both
      NMDAR activation in the VTA and VTA/hippocampus dopaminergic connections are
      essential for the morphine-evoked potentiation and CPP. These findings suggest
      that NMDAR signalings in the midbrain play a key role in regulating dopamine
      mediated hippocampal synaptic plasticity underlying drug-induced associative
      memory. 

PMID- 23163243
TI  - A systematic review of the relationships between family functioning, pubertal
      timing and adolescent substance use.
AB  - AIMS: Experiences linked to poor family functioning and pubertal timing have each
      been associated with increased risk of substance misuse in adolescence. However,
      it remains unclear to what extent family functioning and pubertal timing combine
      to put adolescents at particular risk. METHOD: A systematic review was planned,
      undertaken and reported according to the 27 items of the PRISMA statement.
      Databases World of Knowledge, PsycINFO and PubMed were searched. Fifty-eight
      papers were retained and are discussed in this review after screening titles,
      abstracts and full papers against pre-established exclusion criteria. RESULTS:
      The combination of off-time pubertal timing and poor parent-adolescent
      relationship quality has been related to higher levels of substance use. However,
      this is an under-studied area of research and the evidence is less strong for
      boys than girls. CONCLUSIONS: Adolescents experiencing both poor parent
      adolescent relationship quality and off-time pubertal timing may represent a high
      risk group that can benefit from approaches aimed at reducing risk of substance
      misuse.

PMID- 23163244
TI  - A new cyclohexylacetic acid derivative from the aerial parts of Emilia
      sonchifolia.
AB  - A new cyclohexylacetic acid derivative, named 2-{4-hydroxy-7-oxabicyclo [2.2.1]
      heptanyl}-acetic acid (1), was isolated from Emilia sonchifolia, together with a
      known analogue, 2-(1,4-dihydroxy cyclohexanyl)-acetic acid (2). Their structures
      were determined on the basis of spectroscopic techniques including IR, NMR, HR
      ESI-MS and X-ray diffraction.

PMID- 23163245
TI  - Fire mosaics and reptile conservation in a fire-prone region.
AB  - Fire influences the distribution of fauna in terrestrial biomes throughout the
      world. Use of fire to achieve a mosaic of vegetation in different stages of
      succession after burning (i.e., patch-mosaic burning) is a dominant conservation
      practice in many regions. Despite this, knowledge of how the spatial attributes
      of vegetation mosaics created by fire affect fauna is extremely scarce, and it is
      unclear what kind of mosaic land managers should aim to achieve. We selected 28
      landscapes (each 12.6 km(2) ) that varied in the spatial extent and diversity of
      vegetation succession after fire in a 104,000 km(2) area in the semiarid region
      of southeastern Australia. We surveyed for reptiles at 280 sites nested within
      the 28 landscapes. The landscape-level occurrence of 9 of the 22 species modeled
      was associated with the spatial extent of vegetation age classes created by fire.
      Biogeographic context and the extent of a vegetation type influenced 7 and 4
      species, respectively. No species were associated with the diversity of
      vegetation ages within a landscape. Negative relations between reptile occurrence
      and both extent of recently burned vegetation (<=10 years postfire, n = 6) and
      long unburned vegetation (>35 years postfire, n = 4) suggested that a coarse
      grained mosaic of areas (e.g. >1000 ha) of midsuccessional vegetation (11-35
      years postfire) may support the fire-sensitive reptile species we modeled. This
      age class coincides with a peak in spinifex cover, a keystone structure for
      reptiles in semiarid and arid Australia. Maintaining over the long term a coarse
      grained mosaic of large areas of midsuccessional vegetation in mallee ecosystems
      will need to be balanced against the short-term negative effects of large fires
      on many reptile species and a documented preference by species from other
      taxonomic groups, particularly birds, for older vegetation.

PMID- 23163246
TI  - Simultaneous measurements of H+ and O2 fluxes in Zostera marina and its
      physiological implications.
AB  - Zostera marina (eelgrass) is an important ecological component of many shallow,
      temperate lagoons. Evidence suggests that Z. marina has a high bicarbonate
      utilization capability, which could be promoted by possible proton extrusion and
      the consequent formation of an 'acid zone' in the apoplastic space (unstirred
      layer) of its leaves. It has been found that 50 mM of the buffer Tris
      significantly inhibited the photosynthetic O(2) evolution of Z. marina and it was
      proposed that this was because of Tris's ability to bond with protons outside the
      cell wall. To investigate if H(+) played an important role in the photosynthetic
      carbon utilization of Z. marina, it is very important to simultaneously monitor
      the photosynthesis status and possible H(+) fluxes. However, probably because of
      the lack of suitable techniques, this has never been attempted. In this study,
      experiments were undertaken on Z. marina by monitoring H(+) and O(2) fluxes and
      the relative electron transport rates during light-dark transition. During stable
      photosynthesis, in addition to an obvious O(2) outflow, there was a significant
      net H(+) influx connected to Z. marina photosynthesis. The inhibitory effects of
      both Tris and respiration inhibitors on apparent O(2) evolution of Z. marina were
      confirmed. However, evidence did not support the proposed Tris inhibition
      mechanism.

PMID- 23163247
TI  - Paracellular drug absorption enhancement through tight junction modulation.
AB  - INTRODUCTION: Inclusion of absorption-enhancing agents in dosage forms is one
      approach to improve the bioavailability of active pharmaceutical ingredients with
      low membrane permeability. Tight junctions are dynamic protein structures that
      form a regulated barrier for movement of molecules through the intercellular
      spaces across the intestinal epithelium. Some drug absorption enhancers are
      capable of loosening tight junctions and thereby facilitate paracellular
      absorption of drug molecules. AREAS COVERED: The physiology of tight junctions as
      well as the mechanisms through which tight junctions can be modulated is
      discussed. Selected tight junction modulators are specifically described
      including chelating agents (e.g., ethylenediaminetetraacetic acid), cationic
      polymers (e.g., chitosan and derivatives), toxins (e.g., zonula occludens toxin),
      and plant-derived materials (e.g., Aloe vera gel). EXPERT OPINION: As more and
      more drugs are developed with low membrane permeability, new interest is
      generated in finding ways to enhance their absorption. The progress made in
      comprehending the function and structure of tight junctions has contributed to
      advances in terms of enhanced drug delivery through the paracellular pathway.
      Although tight junction modulation holds great potential for effective oral
      delivery of poorly absorbable drugs, many challenges still need to be overcome
      before more clinically successful formulations could be produced.

PMID- 23163248
TI  - Randomized controlled trials in adult traumatic brain injury.
AB  - BACKGROUND: To optimize strategies for achieving the effectiveness of
      interdisciplinary interventions, this study conducted a comprehensive literature
      review of all Randomized Controlled Trials (RCT) in adults with traumatic brain
      injury (TBI) over the past 30 years. METHOD: Three major databases including
      Medline, PsycINFO and CINAHL were searched, yielding 1176 peer reviewed
      publications. One hundred RCTs were included, encompassing 55 pharmacologic and
      non-pharmacologic acute phase trials and 45 rehabilitation and pharmacologic post
      acute trials. RESULTS: The majority of acute phase pharmacologic or non
      pharmacologic trials (40/55) showed either no effect or adverse effect on TBI
      outcomes. Several trials involving early nutritional therapy or pre-hospital
      rapid intubation demonstrated significant treatment effects. The effect of
      decompressive craniectomy, therapeutic hypothermia and osmotic therapy remained
      controversial. The majority of post-acute phase trials (36/45), consisting of
      cognitive rehabilitation, physical rehabilitation and pharmacotherapy, produced
      various beneficial treatment effects. CONCLUSION: The data indicate that several
      active interventions during the acute phase of TBI are likely to be more
      effective than pharmacotherapy, whereas a comprehensive rehabilitation approach
      is preferred in post-acute phase TBI management. Great progress has been made in
      understanding the heterogeneous injury mechanisms as well as the complexity of
      medical management and rehabilitation following the recovery course of TBI.

PMID- 23163249
TI  - Lack of long-term fMRI differences after multiple sports-related concussions.
AB  - INTRODUCTION: Mild traumatic brain injury (mTBI) or concussion has been acutely
      associated with several cognitive symptoms, including deficits in response
      inhibition, working memory and motor performance. The pervasiveness of these
      cognitive symptoms has been more controversial. The effects of multiple
      concussions on neuropsychological functioning and brain activation following at
      least 6-months post-mTBI were examined. METHODS: Twenty right-handed male
      athletes with a history of at least two concussions and 20 age/pre-morbid
      IQ/athletic-experience matched controls underwent neuropsychological assessment
      and fMRI scanning where they performed versions of a colour-word Stroop
      interference task, an operation-span working memory task and a finger-tapping
      task. RESULTS: The Attention index score on the Repeatable Battery for the
      Assessment of Neuropsychological Status (RBANS) was lower for the concussion
      group, but only at liberal statistical threshold. Total RBANS score approached
      statistical significance. Reaction time during neurobehavioural tasks was similar
      across groups, but accuracy was reduced in the concussed group on the working
      memory task. Despite expected activation patterns within each group, there were
      no group differences in neural activation on any functional tasks using either
      whole-brain or ROI-specific analyses at liberal statistical thresholds.
      CONCLUSION: There were minimal differences between the two closely matched
      groups. Results point to the relative plasticity of younger adults' cognitive
      abilities following concussion.

PMID- 23163250
TI  - Treatment costs and productivity losses caused by traumatic brain injuries.
AB  - OBJECTIVE: To estimate the magnitude and relative importance of hospital
      treatment costs and productivity losses caused by traumatic brain injuries
      (TBIs). PATIENTS: A total of 155 patients with new TBI diagnoses admitted to
      Turku University Hospital were systematically sampled. METHODS: Hospital costs
      were determined by collecting detailed data from patient records and applying the
      actual cost from the hospital administration. For estimating the productivity
      losses, the age of retirement was adjusted according to the age- and sex-specific
      retirement probability. RESULTS: Median treatment costs per TBI patient were
      ?5429, surgery ?1600 and other costs ?3651. Overall treatment costs for severe
      brain injuries were significantly (p < 0.01) higher than for less severe cases.
      Median production losses due to early retirement were estimated to be ?1.19
      million per TBI patient, significantly (p < 0.03) lower among less severe than
      among the severe cases. Age, sex and severity of TBI could explain only 9% of the
      variation in treatment costs, but explained 73% of the variation in production
      losses. CONCLUSIONS: Indirect productivity losses form the great majority of the
      overall economic burden of TBI to society. The direct treatment costs in tertiary
      level hospitals also impose a considerable burden on the healthcare sector.

PMID- 23163251
TI  - Evaluating communication training for paid carers of people with traumatic brain
      injury.
AB  - PRIMARY OBJECTIVE: To evaluate the effectiveness of a communication training
      programme for paid carers to improve their conversational interactions with
      people with TBI. RESEARCH DESIGN: Single blinded randomized controlled study.
      METHODS AND PROCEDURES: Ten paid carers were randomly selected from a post-acute
      residential rehabilitation programme and allocated to either a training or
      control group. Training comprised a 17-hour programme (across 8 weeks) with
      conversational interactions (i.e. structured and casual) between paid carers and
      people with TBI videotaped pre-training, post-training and at 6-months follow-up.
      Interactions were rated on the Adapted Measure of Support in Conversation (MSC),
      Adapted Measure of Participation in Conversation (MPC) and Global Impression
      Scales of conversation. MAIN OUTCOMES AND RESULTS: Trained paid carers were more
      able to acknowledge and reveal the competence of people with TBI. Conversations
      were perceived as more appropriate, interesting and rewarding compared to the
      control group. Improvements were confined to the structured conversation and were
      maintained for 6 months. CONCLUSIONS: Training paid carers has a positive effect
      on improving conversational interactions with people with TBI in a long-term care
      facility. These improvements can help to foster increased independence for the
      person with TBI in the home and community.

PMID- 23163252
TI  - Presumed non-accidental injury with retinal haemorrhages--findings from a
      tertiary referral centre in the United Kingdom.
AB  - AIM: To describe the clinical and demographic features of patients with retinal
      haemorrhages from presumed non-accidental injury (NAI) at a tertiary referral
      centre in Leeds over a 2-year period. METHODS: All patients with retinal
      haemorrhages from presumed NAI between 1 January 2007 and 31 December 2008 were
      retrospectively identified from the hospital RetCam(r) (Clarity Medical System,
      Pleasanton, CA, USA) database. Case-notes, fundus photographs and radiological
      studies were retrieved for all patients and examined. RESULTS: Over the study
      period, 14 infants had retinal haemorrhages secondary to presumed NAI. All were
      male with a mean age of 18 +/- 15 weeks (range 2-47) and came from areas with a
      mean Index of Multiple Deprivation (IMD 2007) rank of 34 +/- 27% (range 0.97-68).
      Seizure/collapse was the reason for presentation in 71% (10/14). Retinal
      haemorrhages were bilateral in 64% (9/14) and unilateral in 36% (5/14). They were
      single-layered in 71% (10/14) and multi-layered in 29% (4/14). Subdural
      haemorrhages were found in 93% (13/14) and were symmetrical in 77% (10/13).
      Skeletal survey was positive in 28% (4/14). CONCLUSIONS: In the context of
      presumed NAI, there is a strong association between presence of retinal
      haemorrhages and the likelihood of underlying subdural haemorrhage. In this
      region, male infants under 12 months, from deprived areas, appear to constitute a
      vulnerable group.

PMID- 23163255
TI  - Emotional true and false memories in children with callous-unemotional traits.
AB  - Several studies have found that children with callous-unemotional (CU) traits
      have a deficit in processing emotionally negative material. The present study
      examined whether this deficit also affects emotional memory. Twenty-two children
      with low CU traits and 24 children with high CU traits between 8 and 12 years of
      age were selected from a community sample and presented with neutral and negative
      emotional words, using the Deese-Roediger-McDermott paradigm. On true recall,
      there was no difference between the groups. Both groups had higher true recall
      rates for the neutral word lists than for the negative lists. However, on false
      recall, although there were no group differences for neutral word lists, the high
      CU group recalled significantly fewer critical lures on the negative word lists
      than the low CU group. Furthermore, the high CU group had significantly less
      false recall on the negative word lists compared to the neutral word lists, while
      the low CU group showed no difference in false recall between the word lists.
      These results indicate that children with high CU traits have no deficiencies in
      true memory performance, yet are less susceptible to developing false memories
      concerning emotionally negative material.

PMID- 23163256
TI  - Bioactive ergostanoids and a new polyhydroxyoctane from Lentinus polychrous
      mycelia and their inhibitory effects on E2-enhanced cell proliferation of T47D
      cells.
AB  - From mycelia of Lentinus polychrous, a Thai local edible mushroom cultured under
      solid-state fermentation, a new compound, 6-methylheptane-1,2,3,4,5-pentaol (1),
      and five ergostanoids, namely (22E,24R)-ergosta-7,22-dien-3beta,5alpha,6beta
      triol (2), 3beta,5alpha-dihydroxy-(22E,24R)-ergosta-7,22-dien-6-one (3), ergosta
      4,6,8(14),22-tetraen-3-one (4), (3beta,5alpha,8alpha,22E)-5,8-diepoxy-ergosta
      6,22-dien-3-ol (5) and 5,8-epidioxy-(3beta,5alpha,8alpha,22E)-ergosta-6,9(11),22
      trien-3-ol (6), was isolated and characterised. The compounds were determined for
      their oestrogenic and anti-oestrogenic activities by using human breast cancer
      T47D cells. All compounds had no oestrogenic activity but exhibited suppressive
      effect on oestradiol-enhanced cell proliferation. Among these compounds, only 4
      significantly competed with oestradiol in the binding to oestrogen receptors
      (ERs) with higher selectivity to ERalpha than ERbeta. These results may suggest
      that most compounds suppressed this oestradiol-enhanced T47D proliferation via
      other mechanisms rather than ER binding. 

PMID- 23163257
TI  - Post-thermocycling shear bond strength of a gingiva-colored indirect composite
      layering material to three implant framework materials.
AB  - OBJECTIVE: To evaluate shear bond strength of a gingiva-colored indirect
      composite to three implant framework materials, before and after thermocycling,
      and verify the effect of surface pre-treatment for each framework. MATERIALS AND
      METHODS: Commercially pure titanium (CP-Ti), American Dental Association (ADA)
      type 4 casting gold alloy (Type IV) and zirconia ceramics (Zirconia) were
      assessed. For each substrate, 96 disks were divided into six groups and primed
      with one of the following primers: Alloy Primer (ALP), Clearfil Photo Bond (CPB),
      Clearfil Photo Bond with Clearfil Porcelain Bond Activator (CPB+Activator),
      Estenia Opaque Primer (EOP), Metal Link (MLP) and V-Primer (VPR). The specimens
      were then bonded to a gingiva-colored indirect composite (Ceramage Concentrate
      GUM-D). Shear bond strengths were measured at 0 and 20 000 thermocycles and data
      were analyzed with the Steel-Dwass test and Mann-Whitney U-test. RESULTS: Shear
      bond strengths were significantly lower after thermocycling, with the exception
      of Type IV specimens primed with CPB (p = 0.092) or MLP (p = 0.112). For CP-Ti
      and Zirconia specimens, priming with CPB or CPB+Activator produced significantly
      higher bond strengths at 0 and 20 000 thermocycles, as compared with the other
      groups. For Type IV specimens, priming with ALP or MLP produced higher bond
      strengths at 0 and 20 000 thermocycles. CONCLUSIONS: Shear bond strength of a
      gingiva-colored indirect composite to CP-Ti, gold alloy and zirconia ceramics was
      generally lower after thermocycling. Application of a hydrophobic phosphate
      monomer and polymerization initiator was effective in maintaining bond strength
      of CP-Ti and zirconia ceramics. Combined use of a thione monomer and phosphoric
      monomer enhanced the durable bond strength of gold alloy.

PMID- 23163258
TI  - Surgical results of patients with unilateral superior oblique palsy presenting
      with large hypertropias.
AB  - PURPOSE: Surgical management of superior oblique palsy (SOP) is challenging
      because of combined vertical, horizontal, and torsional misalignment. The authors
      report the surgical results of patients with large primary position hypertropias
      (> 20 prism diopters [PD]) due to unilateral SOP. METHODS: Criteria for success
      included correction of the anomalous head posture, primary position alignment
      between orthotropia and 6 PD of undercorrection, and no reoperation required for
      residual deviations in any direction of gaze. RESULTS: Forty-five patients met
      inclusion criteria. Mean preoperative alignment in primary gaze was 26.5 +/- 6.5
      PD compared to 3.0 +/- 4.4 PD postoperatively (P < .001). Twenty-three (51%)
      cases met the criteria for success with one operation. Of the patients who had
      single muscle surgery, 14% had a successful outcome, with a mean 67% (17.3 PD)
      reduction in hypertropia. Of patients who underwent simultaneous multiple muscle
      surgery, 58% met the criteria for a successful result, with a mean 92% (24.6 PD)
      reduction in primary gaze hypertropia. Success was the highest in patients who
      underwent ipsilateral inferior oblique combined with contralateral inferior
      rectus recessions with (60% success) or without (65% success) a Harada-Ito
      procedure. CONCLUSION: Undercorrections are frequent following surgery for
      unilateral SOP with preoperative deviations greater than 20 PD in primary
      position, especially after single-muscle surgery. Simultaneous multiple muscle
      surgery rarely results in overcorrection and is recommended in patients with SOP
      and more than 20 PD of hypertropia in primary position.

PMID- 23163259
TI  - Strabismus in craniosynostosis.
AB  - Strabismus is common in craniosynostosis, with rates from 39% to 90.9% in
      Crouzon, Apert, Pfeiffer, and Saethre-Chotzen syndromes. This article reviews the
      epidemiology of strabismus in these disorders and discusses competing theories of
      the mechanism, including absent muscles, excyclorotation of muscles, and
      instability of muscle pulleys. The authors then review options for surgical
      treatment of the often complex ocular misalignment in these disorders.

PMID- 23163260
TI  - An introduction to advances in ocular imaging.

PMID- 23163261
TI  - Intraoperative wavefront aberrometry in cataract surgery.
AB  - Intraoperative wavefront aberrometry is a relatively new technology that aims to
      improve refractive outcomes following cataract surgery by optimizing the
      spherical power of the intraocular lens implant or calculating the appropriate
      axis and power of toric lenses during cataract surgery in an aphakic state. This
      article reviews the literature on intraoperative wavefront aberrometry and
      provides a critical assessment of the benefits and shortcomings of that
      technology.

PMID- 23163262
TI  - Confocal microscopy of corneal dystrophies.
AB  - In vivo confocal microscopy (IVCM) of the cornea is becoming an indispensable
      tool in the cellular study of corneal physiology and disease. This technique
      offers non-invasive imaging of the living cornea with images comparable to that
      of ex vivo histology. The ability to provide high-resolution images of all layers
      in the living cornea has resulted in new discoveries of corneal pathology at the
      cellular level. The IVCM analysis of corneal dystrophies is of importance to
      clinicians, as current methods of diagnosis involve slit-lamp characteristics,
      genetic analysis, and invasive biopsy. IVCM is helpful in evaluating the
      morphological characteristics of corneal dystrophies at the histological level
      and may be helpful in diagnosis, determination of progression, and understanding
      the pathophysiology of disease. The purpose of this review is to describe the
      principles, applications, and clinical correlation of IVCM in the study of
      corneal dystrophies.

PMID- 23163263
TI  - Imaging of pediatric corneal diseases.
AB  - Ocular imaging technologies continue to evolve and play increasingly important
      roles in both the diagnosis and management of corneal pathology. In addition to
      improved documentation of exam findings using increasingly better resolution
      photographs, newer modalities, including specular and confocal microscopy, can
      facilitate diagnosis by imaging single cell layers within the cornea. Anterior
      segment optical coherence tomography (OCT) and ultrasound biomicroscopy (UBM) can
      image structures in the cornea and anterior segment which may not otherwise be
      visible. This is particularly useful in patients with opaque corneas. The ability
      to topographically map the cornea allows for more accurate pre- and post
      operative planning, especially in patients with corneal ectasia. As these
      technologies develop, their use in specific patient populations, such as
      children, must be optimized. In this report, we provide an updated analysis of
      selected imaging modalities used in the diagnosis and management of pediatric
      corneal pathology.

PMID- 23163264
TI  - The evaluation of patients with traumatic cataracts by ultrasound technologies.
AB  - Surgery for traumatic cataracts is a potentially complex procedure. Clinically,
      traumatic cataracts may be difficult to thoroughly assess due to the presence of
      other significant ocular damage including corneal scars, posterior synechiae, and
      vitreous hemorrhage. Frequently, surgery involves surprises regarding the
      integrity of the posterior capsule and zonular structure. Careful ophthalmic
      imaging using ultrasound technologies may result in finer pre-operative detail
      regarding lens support structures, and may therefore give the surgeon the
      advantage when planning surgery. Imaging techniques most applicable to pre
      operative evaluation include B scan ultrasound, 20MHz ultrasound, and ultrasound
      biomicroscopy. Important modifications to technique that can be made depending on
      the integrity of lens support structures include adjustment of wound location,
      adjustment in the technique for cataract removal, and possible use of a capsular
      tension ring.

PMID- 23163265
TI  - X-linked juvenile retinoschisis in females and response to carbonic anhydrase
      inhibitors: case report and review of the literature.
AB  - A 63 year old woman was referred to the retina clinic after her vision failed to
      improve in her left eye after cataract surgery. X-linked retinoschisis was
      diagnosed in the patient after her retina exam revealed an area of retinoschisis
      and a foveal cyst. The OCT confirmed the macular cyst and the ERG showed loss of
      B waves. The florescein angiogram showed no significant perifoveal leakage. Her
      foveal cyst resolved after treatment with carbonic anhydrase inhibitors. The
      patient's son was examined and his ophthalmologic exam, ERG and imaging findings
      were consistent with X-linked retinoschisis. However, his bilateral foveal cysts
      did not respond to treatment with carbonic anhydrase inhibitors. X-linked
      retinoschisis is a very rare disease in women due to its X-linked recessive
      inheritance and the foveal cysts associated with it can respond to carbonic
      anhydrase inhibitors.

PMID- 23163266
TI  - Practical applications of anterior segment optical coherence tomography imaging
      following corneal surgery.
AB  - Anterior segment optical coherence tomography (AS-OCT) has recently emerged as an
      important modality for imaging of the cornea. Since its introduction less than a
      decade ago, it has been clinically used for the diagnosis and management of an
      expanding number of corneal conditions. In this review, we will discuss the
      applications of anterior segment optical coherence tomography after corneal
      surgery, focusing on penetrating and lamellar keratoplasty, keratoprosthesis,
      intracorneal ring segments, collagen cross-linking and refractive surgery.
      Anterior segment optical coherence tomography is useful in evaluating outcomes,
      detecting adverse events, determining prognosis, guiding management decisions,
      and surgical planning.

PMID- 23163267
TI  - Current and potential applications of anterior segment optical coherence
      tomography in contact lens fitting.
AB  - Optical coherence tomography (OCT) is a non-invasive, high-resolution and high
      speed imaging modality that has enjoyed rapid growth in ophthalmology since its
      development 20 years ago. Contact lens fitting is traditionally based on trial
      lenses, which is expensive and time-consuming. Modern anterior segment OCT is
      capable of generating three-dimensional ocular surface maps of the cornea and
      sclera with potential application in contact lens fitting. This paper reviewed
      the history, the ophthalmic applications, and the most recent advancement in
      three-dimensional anterior segment OCT. There is very limited literature of OCT
      in contact lens fitting to date. This review anticipates an increase in this
      application in the near future.

PMID- 23163268
TI  - In vivo confocal microscopy in dry eye disease and related conditions.
AB  - A new era of ocular imaging has recently begun with the advent of in vivo
      confocal microscopy (IVCM), shedding more light on the pathophysiology,
      diagnosis, and potential treatment strategies for dry eye disease. IVCM is a
      noninvasive and powerful tool that allows detection of changes in ocular surface
      epithelium, immune and inflammatory cells, corneal nerves, keratocytes, and
      meibomian gland structures on a cellular level. Ocular surface structures in dry
      eye-related conditions have been assessed and alterations have been quantified
      using IVCM. IVCM may aid in the assessment of dry eye disease prognosis and
      treatment, as well as lead to improved understanding of the pathophysiological
      mechanisms in this complex disease. Further, due to visualization of subclinical
      findings, IVCM may allow detection of disease at much earlier stages and allow
      stratification of patients for clinical trials. Finally, by providing an
      objective methodology to monitor treatment efficacy, image-guided therapy may
      allow the possibility of tailoring treatment based on cellular changes, rather
      than on clinical changes alone.

PMID- 23163269
TI  - Anterior segment imaging and the intraocular pressure lowering effect of cataract
      surgery for open and narrow angle glaucoma.
AB  - Anterior segment imaging modalities including anterior segment optical coherence
      tomography (AS-OCT) and ultrasound biomicroscopy (UBM) are increasingly
      widespread, and can quantify several parameters of the anterior segment, such as
      anterior chamber depth and angle anatomy. These parameters are important to
      assess, particularly in patients with forms of narrow angle glaucoma. In many
      cases of open and narrow angle glaucoma, cataract extraction has been shown to
      result in favorable modification of these parameters, and a lasting decrease in
      intraocular pressure. Anterior segment imaging has the ability to enable the
      development of predictive models regarding the potential intraocular pressure
      lowering effect of cataract extraction in a given individual.

PMID- 23163270
TI  - The use of anterior segment imaging after trabeculectomy.
AB  - Evaluation of patients after trabeculectomy can be aided by the use of anterior
      segment imaging. Two commonly used forms of imaging are ultrasound biomicroscopy
      (UBM) and optical coherence tomography (OCT). Both modalities can be used to
      assess bleb morphology and how it affects treatment outcome, measure anterior
      chamber biometry, identify the presence of supraciliochoroidal fluid,
      cyclodialysis clefts and malignant glaucoma, and evaluate treatment modalities
      after trabeculectomy such as in laser suture lysis and needling. OCT, with its
      finer resolution, is able to view the bleb wall anatomy in detail and because of
      its non-contact nature can examine the eye sooner after trabeculectomy. UBM, on
      the other hand, is superior for the visualization of deeper structures such as
      the ciliary body and posterior chamber essential to identify malignant glaucoma.

PMID- 23163271
TI  - Macular imaging for glaucoma using spectral-domain optical coherence tomography:
      a review.
AB  - Since its introduction, optical coherence tomography (OCT) has become widely used
      and accepted as an imaging modality to detect and follow glaucoma, with
      measurement of the peripapillary retinal nerve fiber layer (pRNFL) being the most
      utilized parameter. Up until recently, macular thickness parameters have not been
      commonly used in glaucoma due to results of earlier studies with time-domain OCT
      (TD-OCT) that revealed macular imaging to be inferior to pRNFL in the diagnosis
      of glaucoma. The recent advent of spectral-domain OCT (SD-OCT) has renewed
      interest in the potential uses of macular imaging in glaucoma due to its ability
      to better segment and measure individual retinal layers. Multiple studies have
      been performed in the last few years to investigate the diagnostic ability,
      reproducibility, and limitations of these new SD-OCT macular parameters. The
      purpose of this paper is to review the findings of those studies to assess the
      current utility of macular SD-OCT in glaucoma. Overall, SD-OCT has been shown to
      have higher reproducibility than TD-OCT, and though there have been some
      conflicting reports, the majority of studies seem to concur that the diagnostic
      sensitivity of SD-OCT macular parameters is at least comparable to TD-OCT and
      other SD-OCT parameters.

PMID- 23163272
TI  - Dynamic imaging of paralytic eyelid disorders.
AB  - PURPOSE: Eyelid dysmotility may result from trauma, tumors, inflammation,
      infection, and a variety of other conditions. In these cases, a mechanical effect
      is disrupting a normal neuromuscular apparatus. Dysmotility can also be caused by
      paralytic eyelid disorders; included in this broad category are neurologic and
      myogenic disorders of eyelid opening and/or closure. Secondary effects include
      spastic eyelid closure and synkinesis syndromes. These conditions, by definition,
      are disorders of movement, and can only be studied adequately using dynamic
      imaging techniques. METHODS: A comprehensive literature search was performed on
      PubMed. Ninety abstracts were reviewed. RESULTS: Dynamic eyelid imaging has
      evolved dramatically over the past two decades, at least partially due to the
      rise of inexpensive digital technology. Magnetic search coil imaging, high- and
      low-speed videography, electromyography, and high-resolution microscopy coil
      magnetic resonance imaging each has its advantages and disadvantages, an
      understanding of which will guide appropriate selection of technology in any
      given clinical situation. CONCLUSIONS: Dynamic eyelid imaging is useful to study
      dysmotility. The optimal technique depends upon the clinical setting and the
      physiologic or pathologic topic of interest. To our knowledge, a report of this
      type has not been previously summarized.

PMID- 23163273
TI  - Update on imaging of the lacrimal drainage system.
AB  - Epiphora is a common problem seen by the ophthalmologist. There are numerous
      etiologies of a watering eye, and the underlying diagnosis is not always clear. A
      variety of in-office examination techniques and procedures exist to aid with
      diagnosis and determination of appropriate therapy, but sometimes the diagnosis
      remains elusive, or an instituted therapy fails. Lacrimal imaging, particularly
      in these cases, can be helpful in assessing the function and anatomy of the
      lacrimal drainage system. This review serves to examine the literature of the
      last 10 years concerning imaging of the lacrimal drainage system.

PMID- 23163274
TI  - The use of fourth-generation optical coherence tomography in multiple sclerosis:
      a review.
AB  - Optical coherence tomography (OCT) has been routinely used to obtain high spatial
      resolution images of the retina and choroid non-invasively. Within the past
      decade, a fourth-generation OCT device using Fourier domain (FD) analysis has
      been developed that provides higher velocity and higher axial resolution images
      with better reproducibility than the previous generation time domain (TD) OCT
      technology. This review addresses the use of fourth-generation, FD ocular OCT in
      patients with multiple sclerosis.

PMID- 23163275
TI  - Neuro-imaging: a review for the general ophthalmologist.
AB  - The diagnosis of many neuro-ophthalmic conditions is facilitated with neuro
      imaging. The two main modalities are Computed Tomography (CT) and Magnetic
      Resonance Imaging (MRI). Clinicians who refer patients for either of these
      techniques must not only know which of them to choose, but also where the imaging
      should be performed (e.g. brain, orbit), whether or not contrast is indicated,
      and if angiography should be supplemented. These complexities often result in
      imaging studies that are either unneeded or unhelpful. The goal of this
      manuscript is to provide a practical set of guidelines for the general
      ophthalmologist of how to choose the correct parameters for neuro-imaging
      studies.

PMID- 23163276
TI  - Lipofuscin and the principles of fundus autofluorescence: a review.
AB  - Fundus autofluorescence is a non-invasive imaging modality that measures
      lipofuscin that has accumulated in the retinal pigment epithelium (RPE).
      Excessive lipofuscin in the RPE is a common pathway found in several diseases
      including Stargardt's disease and age-related macular degeneration. This review
      discusses the role of photooxidative damage in the development of lipofuscin and
      the principles of fundus autofluorescence.

PMID- 23163277
TI  - Near infrared autofluorescence imaging of retinal diseases.
AB  - Near infrared autofluorescence (excitation 787 nm, emission >800 nm) is a non
      invasive imaging technology that provides information on the distribution of
      melanin within the retinal pigment epithelial cell/choroid complex. This review
      contains an introduction to near infrared autofluorescence imaging methods.
      Characteristics of near infrared imaging in a variety of retinal diseases,
      including age-related macular degeneration, choroidal nevus, retinal
      degenerations, retinal dystrophies, central serous chorioretinopathy,
      pseudoxanthoma elasticum and chloroquine retinopathy, are summarized.

PMID- 23163278
TI  - Enhanced depth imaging optical coherence tomography in age-related macular
      degeneration.
AB  - Imaging of the choroidal layer has been limited with the conventional commercial
      SD-OCTs. Enhanced depth imaging optical coherence tomography (EDI-OCT) is a
      modification of the standard spectral-domain OCT (SD-OCT) technique that enables
      better non-invasive imaging of the choroid. This review contains an introduction
      of EDI imaging technique and principles and summarizes the findings of EDI-OCT
      imaging in age-related macular degeneration.

PMID- 23163279
TI  - Portable optical coherence tomography in management of vitreoretinal diseases:
      current developments, indications, and implications.
AB  - The advent of optical coherence tomography (OCT) technology has greatly enhanced
      our understanding of vitreoretinal diseases; it has become a routine diagnostic
      imaging method for the evaluation of vitreoretinal abnormalities and injuries in
      adult and pediatric patients. The use of OCT has recently been extended beyond
      the offices and clinics to perioperative and intraoperative settings. The new
      development in high-resolution and high-speed spectral domain OCT, along with the
      improvement in portability, has made the device more valuable than ever before.
      Our article summarizes the current development of the portable OCT devices in
      clinical, perioperative, and intraoperative settings in the management of
      vitreoretinal diseases.

PMID- 23163280
TI  - Ultra-wide field retinal imaging in detection, classification, and management of
      diabetic retinopathy.
AB  - Current ultra-wide field (UWF) retinal imaging systems utilize scanning laser
      ophthalmoscope technology combined with an ellipsoidal mirror to capture up to
      200 degrees of the retina in a single image. When compared with mydriatic ETDRS
      protocol, 7 standard field photographs and clinical examination, nonmydriatic UWF
      images appear to have excellent agreement in allowing the detection and
      classification of diabetic retinopathy (DR), although larger, definitive
      validation studies are still forthcoming. UWF imaging and angiography allow
      visualization of peripheral retinal nonperfusion, vascular leakage and
      neovascularization in patients with DR that may not be captured on 7 standard
      fields. Prospective randomized controlled trials are needed to evaluate whether
      modified laser treatment algorithms based on improved visualization of the
      retinal periphery might improve patient outcomes. Nonmydriatic UWF imaging has
      potential applications for ocular diabetic telehealth programs, but validation of
      newer, more portable, and more affordable UWF imaging models is needed.

PMID- 23163281
TI  - Fundus autofluorescence imaging in posterior uveitis.
AB  - Although the phenomenon of fundus autofluorescence has been known for decades, it
      has only recently been recognized as a measure of retinal pigment epithelial
      function and health. Characteristic fundus autofluorescence patterns have been
      described in eyes affected by inflammation of the posterior segment, and these
      patterns have provided insights into the pathogenesis of posterior uveitis
      entities. In addition, preliminary data indicate that fundus autofluorescence
      characteristics may serve as markers of disease activity, allow prediction of
      visual prognosis, and may help determine the adequacy of therapy. We provide an
      overview of the current state of fundus autofluorescence imaging technology and
      review our current knowledge of fundus autoflourescence findings and their
      clinical use in the posterior uveitis entities.

PMID- 23163282
TI  - Role of OCT in the diagnosis and management of macular edema from uveitis.
AB  - Uveitis is a potentially visually threatening disease accounting for 10% of
      vision loss in the developed world. The most common cause of vision loss in
      patients with uveitis has been shown to be macular edema (ME). The early
      detection and management of ME is critical to preserve vision in these patients.
      Optical coherence tomography (OCT) is a valuable tool in the management of many
      ocular diseases. The use of OCT has revolutionized the diagnosis and management
      of macular edema from a wide variety of ophthalmological diseases, including
      uveitis. In this review, we evaluate the role of OCT in the diagnosis and
      management of uveitic macular edema.

PMID- 23163283
TI  - Utility of ocular ultrasonography in diagnosing infectious endophthalmitis in
      patients with media opacities.
AB  - Assessment of patients with infectious endophthalmitis is frequently limited by
      media opacities, and ocular ultrasonography is routinely performed in this
      setting. We examined the literature to assess the level of evidence for the
      utility of ocular ultrasonography in these patients. Common ultrasonographic
      findings reported include low amplitude mobile echoes, vitreous membranes, and
      thickening of the retina and choroid. Based on the available evidence, we
      conclude that ocular ultrasound may be a useful adjunct in guiding treatment and
      minimizing complications. While positive findings may be confirmatory in cases in
      which the clinical suspicion is high, ocular ultrasound alone cannot be used to
      prove or to exclude the diagnosis of infectious endophthalmitis.

PMID- 23163285
TI  - Paediatric travel medicine: vaccines and medications.
AB  - The paediatric aspects of travel medicine can be complex, and individual advice
      is often required. Nonetheless, children are much more likely to acquire common
      infections than exotic tropical diseases whilst travelling. Important exceptions
      are malaria and tuberculosis, which are more frequent and severe in children.
      Overall, travellers' diarrhoea is the most common illness affecting travellers.
      This review discusses vaccines and medications that may be indicated for children
      who are travelling overseas. It focuses on immunizations that are given as part
      of the routine schedule, as well as those that are more specific to travel.
      Malaria and travellers' diarrhoea are also discussed.

PMID- 23163284
TI  - Curvature forces in membrane lipid-protein interactions.
AB  - Membrane biochemists are becoming increasingly aware of the role of lipid-protein
      interactions in diverse cellular functions. This review describes how
      conformational changes in membrane proteins, involving folding, stability, and
      membrane shape transitions, potentially involve elastic remodeling of the lipid
      bilayer. Evidence suggests that membrane lipids affect proteins through
      interactions of a relatively long-range nature, extending beyond a single annulus
      of next-neighbor boundary lipids. It is assumed the distance scale of the forces
      is large compared to the molecular range of action. Application of the theory of
      elasticity to flexible soft surfaces derives from classical physics and explains
      the polymorphism of both detergents and membrane phospholipids. A flexible
      surface model (FSM) describes the balance of curvature and hydrophobic forces in
      lipid-protein interactions. Chemically nonspecific properties of the lipid
      bilayer modulate the conformational energetics of membrane proteins. The new
      biomembrane model challenges the standard model (the fluid mosaic model) found in
      biochemistry texts. The idea of a curvature force field based on data first
      introduced for rhodopsin gives a bridge between theory and experiment. Influences
      of bilayer thickness, nonlamellar-forming lipids, detergents, and osmotic stress
      are all explained by the FSM. An increased awareness of curvature forces suggests
      that research will accelerate as structural biology becomes more closely entwined
      with the physical chemistry of lipids in explaining membrane structure and
      function.

PMID- 23163286
TI  - Comparison of TPA, bone healing, and intra-articular screw placement using
      conventional nonlocked application of surgeon-contoured versus locked application
      of precontoured TPLO plates in dogs.
AB  - OBJECTIVE: To determine the influence of conventional nonlocked application of
      surgeon-contoured (NL-SXc) and locked-hybrid application of precontoured (L-Pc)-
      TPLO plates on the tibial plateau angle (TPA) immediately postoperatively and
      longterm after tibial plateau leveling osteotomy (TPLO) in dogs as well as to
      evaluate their influence on the incidence of intra-articular screw placement and
      bone healing. STUDY DESIGN: Retrospective, cross-sectional, clinical study.
      ANIMALS: Dogs (n = 101) with cruciate ligament insufficiency that had TPLO.
      METHODS: Collected data included signalment, plate size/type, preoperative
      (PreTPA), postoperative (PostTPA), and recheck TPA (ReTPA). Tibial plateau
      rotation achieved during surgery (RotaTPA = PreTPA-PostTPA) and TPA shift during
      healing (ShiftTPA = ReTPA-PostTPA) were calculated. Radiographic evidence of
      stability and time to radiographic recheck were recorded. Variables were compared
      by plate type using a 2-sample t-test or chi(2)  as appropriate (significance at
      P < .05). RESULTS: Median time to radiographic follow-up was 75 days (range, 43
      2815 days). The remaining data are reported as means. Forty-two stifles had NL
      SXc, 59 stifles had L-Pc. PreTPA of NL-SXc and L-Pc was 28.3 degrees  and 29.1
      degrees , respectively (P = .22). PostTPA (13.2 degrees  and 7.9 degrees ),
      RotaTPA (15.0 degrees  and 21.2 degrees ) and ReTPA (14.9 degrees  and 10.3
      degrees ) for NL-SXc and L-Pc, respectively, were all significantly different (P<
      .0001). ShiftTPA for these constructs (1.7 degrees  and 2.4 degrees ,
      respectively) was not significantly different (P = .25), and 92.1% of dogs were
      considered to have radiographically stable osteotomies at last recheck.
      CONCLUSIONS: A higher degree of tibial plateau rotation was achieved and
      maintained in osteotomies with L-Pc. There was no significant difference in
      ShiftTPA or radiographic osteotomy stability between constructs.

PMID- 23163287
TI  - Healthcare resource usage of schizophrenia patients initiating long-acting
      injectable antipsychotics vs oral.
AB  - OBJECTIVE: To compare hospitalizations and incidence of relapses among patients
      with schizophrenia initiating long-acting injectable (LAI) antipsychotics vs oral
      antipsychotics. METHODS: Patients with schizophrenia initiating LAI
      antipsychotics or oral antipsychotics (index events) were identified from large
      databases (MarketScan; Truven Health Analytics, CA), containing commercial and
      Medicare healthcare claims and their pre-index (12-month baseline period) and
      post-index (12-month follow-up period) hospitalizations and relapse rates were
      compared. Descriptive and bivariate statistics were utilized to compare
      demographics, clinical characteristics, and hospital resource usage among
      cohorts. Multivariate analysis was used to evaluate the impact of initiating LAI
      vs oral antipsychotics on differences in the number of hospitalizations and
      length of stay (LOS) between follow-up and baseline periods. RESULTS:
      Commercially insured patients initiating LAI antipsychotics (n = 394) had
      significant reductions in inpatient healthcare usage after initiating
      antipsychotic therapy: mean number (+/-standard deviation) of all cause
      hospitalizations (1.60 +/- 1.66 vs 0.70 +/- 1.20, p < 0.001), LOS (16.9 +/- 20.7
      vs 6.6 +/- 14.4 days, p < 0.001), schizophrenia-related hospitalizations (1.03 +/
      1.26 vs 0.43 +/- 0.86, p < 0.001), associated LOS (12.3 +/- 17.7 vs 4.8 +/- 12.8
      days, p < 0.001). Patients initiating LAI vs oral antipsychotics (n = 2610) had
      significantly greater reductions during the follow-up period vs baseline period
      in the mean number of all cause hospitalizations (-0.90 +/- 1.77 vs 0.02 +/-
      1.49, p < 0.001), LOS (-10.3 +/- 23.2 vs 0.7 +/- 16.7 days, p < 0.001),
      schizophrenia-related hospitalizations (-0.60 +/- 1.37 vs 0.05 +/- 0.99, p <
      0.001) and associated LOS (-7.5 +/- 20.7 vs 0.6 +/- 12.5 days, p < 0.001). These
      results were further supported by multivariate analyses in which patient
      characteristics were taken into consideration. LIMITATIONS: This study attempted
      to minimize the impact of differences in patient characteristics by having
      patients serve as their own controls in the before vs after comparison followed
      by multivariate regressions, however one still may not be able to account for all
      confounders in this non-randomized study population. CONCLUSION: Patients with
      schizophrenia who initiated LAI vs oral antipsychotics experienced reductions in
      hospitalizations and schizophrenia relapses after drug initiation, which may be
      indicative of improved disease management.

PMID- 23163288
TI  - Long-term outcome of phenobarbital treatment for epilepsy in rural China: a
      prospective cohort study.
AB  - PURPOSE: To evaluate the long-term outcome of phenobarbital treatment for
      convulsive epilepsy in rural China, and to explore factors associated with
      overall seizure outcomes. METHODS: We carried out follow-up assessments of people
      who took part in an epilepsy community management program conducted in rural
      counties of six provinces in China. People with convulsive epilepsy who were
      previously untreated (or on irregular treatment) were commenced on regular
      treatment with phenobarbital. Information was collected using a standardized
      questionnaire by face-to-face interviews of the individuals (and their families
      where necessary). Information collected included treatment status, medication
      change, seizure frequency, and mortality. KEY FINDINGS: Among the 2,455 people
      who participated in the original program, outcomes were successfully ascertained
      during the follow-up assessment in 1986. Among them, 206 had died. Information on
      treatment response was obtained in 1,780 (56% male; mean age 33.9 years, range 3
      84; mean duration of follow-up 6.4 years). Among them, 939 (53%) were still
      taking phenobarbital. The most common reasons for stopping phenobarbital were
      seizure freedom or substantial seizure reduction, socioeconomic reasons, and
      personal preference. Four hundred fifty-three individuals (25%) became seizure
      free for at least 1 year while taking phenobarbital, 88% of whom did so at daily
      doses of 120 mg or below. Four hundred six (23%) reported adverse events, which
      led to withdrawal of phenobarbital in <1%. The most common adverse effects were
      malaise/somnolence (7.4%), dizziness (3%), and lethargy (2.6%). At the follow-up
      assessment, 688 (39%) individuals had been seizure free for at least the previous
      year. People with persistent seizures had significantly longer duration of
      epilepsy and higher number of seizures in the 12 months before treatment. People
      who were taking AED treatment irregularly at recruitment were less likely to
      become seizure-free. SIGNIFICANCE: We observed long-term benefits of regular
      treatment with phenobarbital for convulsive epilepsy in rural China. One hundred
      years after the discovery of its antiepileptic effect, phenobarbital is still
      playing an important role in the management of epilepsy.

PMID- 23163289
TI  - Chemical unfolding of chicken villin headpiece in aqueous dimethyl sulfoxide
      solution: cosolvent concentration dependence, pathway, and microscopic mechanism.
AB  - Unfolding of a protein often proceeds through partial unfolded intermediate
      states (PUIS). PUIS have been detected in several experimental and simulation
      studies. However, complete analyses of transitions between different PUIS and the
      unfolding trajectory are sparse. To understand such dynamical processes, we study
      chemical unfolding of a small protein, chicken villin head piece (HP-36), in
      aqueous dimethyl sulfoxide (DMSO) solution. We carry out molecular dynamics
      simulations at various solution compositions under ambient conditions. In each
      concentration, the initial step of unfolding involves separation of two adjacent
      native contacts, between phenyl alanine residues (11-18 and 7-18). This first
      step induces, under appropriate conditions, subsequent separation among other
      hydrophobic contacts, signifying a high degree of cooperativity in the unfolding
      process. The observed sequence of structural changes in HP-36 on increasing DMSO
      concentration and the observed sequence of PUIS, are in approximate agreement
      with earlier simulation results (in pure water) and experimental observations on
      unfolding of HP-36. Peculiar to water-DMSO mixture, an intervening structural
      transformation (around 15% of DMSO) in the binary mixture solvent retards the
      progression of unfolding as composition is increased. This is reflected in a
      remarkable nonmonotonic composition dependence of RMSD, radius of gyration and
      the fraction of native contacts. At 30% mole fraction of DMSO, we find the
      extended randomly coiled structure of the unfolded protein. The molecular
      mechanism of DMSO induced unfolding process is attributed to the initial
      preferential solvation of the hydrophobic side chain atoms through the methyl
      groups of DMSO, followed by the hydrogen bonding of the oxygen atom of DMSO to
      the exposed backbone NH groups of HP-36.

PMID- 23163290
TI  - Characterizing the aging of biomass burning organic aerosol by use of mixing
      ratios: a meta-analysis of four regions.
AB  - Characteristic organic aerosol (OA) emission ratios (ERs) and normalized excess
      mixing ratios (NEMRs) for biomass burning (BB) events have been calculated from
      ambient measurements recorded during four field campaigns. Normalized OA mass
      concentrations measured using Aerodyne Research Inc. quadrupole aerosol mass
      spectrometers (Q-AMS) reveal a systematic variation in average values between
      different geographical regions. For each region, a consistent, characteristic
      ratio is seemingly established when measurements are collated from plumes of all
      ages and origins. However, there is evidence of strong regional and local-scale
      variability between separate measurement periods throughout the tropical,
      subtropical, and boreal environments studied. ERs close to source typically
      exceed NEMRs in the far-field, despite apparent compositional change and
      increasing oxidation with age. The absence of any significant downwind mass
      enhancement suggests no regional net source of secondary organic aerosol (SOA)
      from atmospheric aging of BB sources, in contrast with the substantial levels of
      net SOA formation associated with urban sources. A consistent trend of moderately
      reduced DeltaOA/DeltaCO ratios with aging indicates a small net loss of OA,
      likely as a result of the evaporation of organic material from initial fire
      emissions. Variability in ERs close to source is shown to substantially exceed
      the magnitude of any changes between fresh and aged OA, emphasizing the
      importance of fuel and combustion conditions in determining OA loadings from
      biomass burning.

PMID- 23163291
TI  - Bile acid-based 1,2,4-trioxanes: synthesis and antimalarial assessment.
AB  - A new series of bile acid-based trioxanes 23a-d, 24a-d, 25a-d, 26a, 26b, and 26d
      have been synthesized and assessed for their antimalarial activity against
      multidrug-resistant Plasmodium yoelii in Swiss mice by oral route. The
      antimalarial activity of these trioxanes showed a strong dependence on the side
      chain length; shortening side-chain length lead to increase in activity. The
      antimalarial activity also showed even stronger dependence on the stereochemistry
      at C3 and C6 (C21 in Figure 5) of the trioxane moiety. Of the two diastereomers
      isolated of each of the trioxanes, more polar one was significantly more active
      than the less polar one. The more polar diastereomer of the trioxanes 26a, 26b,
      and 26d, were the most active compounds of the series. All these three trioxanes
      provided 100% protection at 24 mg/kg*4 days. In this model beta-arteether
      provided 100% and 20% protection at 48 mg/kg*4 days and 24 mg/kg*4 days,
      respectively.

PMID- 23163293
TI  - Evaluation of blood supply operation and infectious disease markers in blood
      donors during the Egyptian revolution.
AB  - BACKGROUND: The Egyptian revolution took place on January 25, 2011. Millions of
      protesters demanded the overthrow of the Egyptian president's regime. Many people
      suffered from life-threatening injuries after violent clashes between police and
      protesters. STUDY DESIGN AND METHODS: The overall management of the blood bank
      operation at Cairo University Hospital was described, in an attempt to evaluate
      blood safety and establish a standard effective plan to manage blood supply
      during crisis. RESULTS: Three days after the uprising, thousands of Egyptians
      rushed to the hospital to alleviate the blood shortage. A total of 3425 units
      were collected in 3 days and thousands of donors were turned away. An error
      delayed processing of 1000 units and they were used as stored whole blood.
      Apheresis platelets were donated by protesters who were particularly motivated to
      donate for two victims with liver injury. The usual positive rate of hepatitis C
      virus (HCV) antibody in Egyptian donors is 3.8%. However, the positive rate of
      HCV markers in the collected units was only 1.6%. The mean age of donors during
      the revolution was 31.7+/-10.4 years while the usual mean age of donors is 39.2+/
      8.5 years. Operating theaters were used only for emergencies. A blood surplus
      developed that met the hospital needs for 1 month. CONCLUSION: Revolution
      resulted in an influx of first-time donors with a relatively low positive rate of
      HCV antibody. To be prepared for disasters, a systematic approach to spread
      donors evenly on a daily basis is needed.

PMID- 23163294
TI  - Speciation of L-DOPA on nanorutile as a function of pH and surface coverage using
      surface-enhanced Raman spectroscopy (SERS).
AB  - The adsorption configuration of organic molecules on mineral surfaces is of great
      interest because it can provide fundamental information for both engineered and
      natural systems. Here we have conducted surface-enhanced Raman spectroscopy
      (SERS) measurements to probe the attachment configurations of DOPA on nanorutile
      particles under different pH and surface coverage conditions. The Raman signal
      enhancement arises when a charge transfer (CT) complex forms between the
      nanoparticles and adsorbed DOPA. This Raman signal is exclusively from the
      surface-bound complexes with great sensitivity to the binding and orientation of
      the DOPA attached to the TiO(2) surface. Our SERS spectra show peaks that
      progressively change with pH and surface coverage, indicating changing surface
      speciation. At low pH and surface coverage, DOPA adsorbs on the surface lying
      down, with probably three points of attachment, whereas at higher pH and surface
      coverage DOPA stands up on the surface as a species involving two attachment
      points via the two phenolic oxygens. Our results demonstrate experimentally the
      varying proportions of the two surface species as a function of environmental
      conditions consistent with published surface complexation modeling. This
      observation opens up the possibility to manipulate organic molecule attachment in
      engineered systems such as biodetection devices. Furthermore, it provides a
      perspective on the possible role of mineral surfaces in the chemical evolution of
      biomolecules on the early Earth. Adsorbed biomolecules on mineral surface in
      certain configurations may have had an advantage for subsequent condensation
      reactions, facilitating the formation of peptides.

PMID- 23163292
TI  - Sea level, topography and island diversity: phylogeography of the Puerto Rican
      Red-eyed Coqui, Eleutherodactylus antillensis.
AB  - Quaternary climatic oscillations caused changes in sea level that altered the
      size, number and degree of isolation of islands, particularly in land-bridge
      archipelagoes. Elucidating the demographic effects of these oscillations
      increases our understanding of the role of climate change in shaping evolutionary
      processes in archipelagoes. The Puerto Rican Bank (PRB) (Puerto Rico and the
      Eastern Islands, which comprise Vieques, Culebra, the Virgin Islands and
      associated islets) in the eastern Caribbean Sea periodically coalesced during
      glaciations and fragmented during interglacial periods of the quaternary. To
      explore population-level consequences of sea level changes, we studied the
      phylogeography of the frog Eleutherodactylus antillensis across the archipelago.
      We tested hypotheses encompassing vicariance and dispersal narratives by
      sequencing mtDNA (c. 552 bp) of 285 individuals from 58 localities, and four
      nuDNA introns (totalling c. 1633 bp) from 173 of these individuals. We found low
      support for a hypothesis of divergence of the Eastern Islands populations prior
      to the start of the penultimate interglacial c. 250 kya, and higher support for a
      hypothesis of colonization of the Eastern Islands from sources in eastern Puerto
      Rico during the penultimate and last glacial period, when a land bridge united
      the PRB. The Rio Grande de Loiza Basin in eastern Puerto Rico delineates a
      phylogeographic break. Haplotypes shared between the PRB and St. Croix (an island
      c. 105 km south-east of this archipelago) likely represent human-mediated
      introductions. Our findings illustrate how varying degrees of connectivity and
      isolation influence the evolution of tropical island organisms.

PMID- 23163295
TI  - Three-dimensional nanographene based on triptycene: synthesis and its application
      in fluorescence imaging.
AB  - A novel kind of three-dimensional (3D) nanographene based on a triptycene
      structure bearing three hexa-peri-hexabenzocoronene (HBC) moieties was
      synthesized efficiently from triiodotriptycene. With the characteristic of
      intrinsic fluorescence, the 3D nanographene was used as a fluorescent agent for
      in vitro and in vivo fluorescence imaging with good antiphotobleaching ability
      and little toxicity.

PMID- 23163297
TI  - Review of cerebellopontine angle medulloblastoma.
AB  - Cerebellopontine angle (CPA) medulloblastomas (MB) are rare lesions with few
      cases previously described in the literature. We report two further cases of CPA
      MB. The patients were a 22-year-old man and a 26-year-old woman with a mass
      developing in the CPA. The preoperative radiological diagnosis was vestibular
      schwannoma in the first case and petrosal meningioma in the second case. The
      patients were operated on through a retrosigmoid approach. The intraoperative
      findings revealed an intra-axial tumour and the histological diagnosis was
      classic type of MB in both cases. We review the literature and discuss
      pathological and radiological features and possible pathogenesis of CPA MB,
      underlining the necessity to consider MB in the differential diagnosis of CPA
      lesions.

PMID- 23163296
TI  - Comparative study of the protective capacity against Salmonella infection between
      probiotic and nonprobiotic Lactobacilli.
AB  - AIMS: To investigate the immunoprotective ability of three Lactobacilli strains
      against Salmonella enterica serovar Typhimurium in a mouse model. To identify the
      probiotic properties involved in the protection against infection caused by this
      pathogen. METHODS AND RESULTS: The immunomodulatory effect of three different
      lactobacilli strains: Lactobacillus (Lact.) casei CRL 431 (probiotic bacterium),
      Lact. delbrueckii subsp. bulgaricus CRL 423 (Lact. bulgaricus) and
      Lact.acidophilus CRL 730 was compared using a mouse model of Salmonella
      infection. Lactobacillus casei continuous administration improved animal
      survival, diminished pathogen spreading outside the intestine, attenuated the
      intestinal inflammation, modulated cytokine profile previous and postinfection
      and increased the expression and secretion of IgA in the gut. Additionally, the
      administration of this lactobacilli increased peritoneal, Peyer's patches and
      spleen macrophages' phagocytic activity in healthy mice and monocyte chemotactic
      protein (MCP-1) released by intestinal epithelial cells in an in vitro assay.
      Although Lact. acidophilus increased the number of IgA-secreting cells previous
      and postinfection, and Lact. bulgaricus increased MCP-1 released by intestinal
      epithelial cells and the phagocytic activity of macrophages, these effects alone
      were not enough to confer protection against Salmonella Typhimurium infection in
      mouse. CONCLUSIONS: Probiotic strain Lact. casei CRL 431 was the one that induced
      protection against Salmonella, by increasing the intestinal barrier function and
      by decreasing the local inflammatory response. SIGNIFICANCE AND IMPACT OF THE
      STUDY: Salmonella spp. constitutes an important agent of foodborne diseases in
      the world. Not all lactobacilli, even with some immunostimulating properties at
      gut level, can protect against Salmonella infection. Lactobacillus casei CRL 431,
      a probiotic bacterium, could be useful as an oral mucosal adjuvant of the immune
      system to improve gut health, especially in the prevention or amelioration of
      Salmonella infections. We demonstrated that there is not a unique mechanism by
      which this protective effect was exerted.

PMID- 23163298
TI  - Radiation-induced anaplastic ependymoma with a remarkable clinical response to
      temozolomide: a case report.
AB  - Radiation-induced gliomas are uncommon and therapeutic options are limited due to
      prior exposure to radiotherapy. Meanwhile, the chemotherapeutic response of
      anaplastic ependymoma, another rare entity in adults, is often disappointing. We
      report on the first recorded case of radiation-induced anaplastic ependymoma, in
      which an excellent clinical response to temozolomide was demonstrated.

PMID- 23163299
TI  - Image-guided stereotactic biopsy of pineal region tumour using CT venography in
      patient with a pacemaker: a technical note.
AB  - Image-guided stereotactic biopsy of pineal region tumours requires careful
      appreciation of neuroanatomy and avoidance of the deep cerebral venous system. A
      patient with a pineal region lesion obstructing the third ventricle and causing
      obstructive hydrocephalus required stereotactic biopsy after cerebrospinal fluid
      (CSF) diversion. The presence of a pacemaker precluded MR Venography. Fine-cut CT
      Venography was performed in its stead and merged with image guidance software,
      and a trajectory was planned avoiding the venous anatomy. Stereotactic biopsy was
      successfully performed without complication, revealing a pineocytoma.

PMID- 23163300
TI  - In situ posterolateral and fibular interbody fusion in high grade
      spondylolysthesis.
AB  - OBJECTIVE: High-grade spondylolysthesis and spondyloptosis management have
      various options. There were no large series reported to support any particular
      treatment modality. The aim of surgery is to get solid bony fusion to get relief
      of instability and its symptoms as well as relief of neurological symptoms. There
      are many treatment options which are associated with technical difficulties and
      high incidence of complications and failures. In situ transsacral fibular graft
      with posterolateral fusion along with posterior decompression is a good surgical
      option. It offers anterior and posterolateral fusion for instability pain and
      relief of neurological symptoms in most of the patients. It is technically
      simple, with no major surgery-related complications. MATERIALS AND METHODS: The
      cases of high-grade spondylolysthesis operated since 2008 with one year minimal
      follow up were included in this study. Six cases were operated during this
      period. All were females in their second and third decade of life. All of them
      had transsacral fibular grafting with posterolateral fusion and decompression.
      One of the cases had additional anterior procedure with sacral widening with bone
      graft. The clinical status and bony fusion has been assessed at the end of one
      year after surgery and also for assessing final outcome. RESULTS: All the
      patients had solid bony fusion with no progression of slip and are pain free and
      relived of neurological symptoms. conclusions: In situ transsacral fibular graft
      with posterolateral fusion and posterior decompression is technically simple
      surgical option with minimal risks and reliable outcome.

PMID- 23163301
TI  - Early life influences on the risk of injecting drug use: case control study based
      on the Edinburgh Addiction Cohort.
AB  - AIMS: To investigate childhood influences on onset of injection drug use. DESIGN:
      Matched case-control study. SETTING: Edinburgh, Scotland. PARTICIPANTS: A total
      of 432 individuals presenting at a community health facility with injection drug
      use and 432 age- and sex-matched non-injecting controls recruited through the
      same facility. MEASUREMENTS: Main exposures considered were family structure and
      experience of public care, carer substance use, physical and sexual victimization
      and conduct problems, all measured at personal interview. The outcome was history
      of adult injection drug use recorded in medical records corroborated at personal
      interview. FINDINGS: Compared to two-parent families all other family structures
      were associated with increased risk of injection drug use, the greatest increased
      risk being associated with public care. Violence, criminality and financial
      problems in the family were also associated with increased risk, as were all
      types of carer substance use. The greatest increased risk was associated with
      markers of early conduct problems, particularly school exclusion and childhood
      contact with the criminal justice system. In multivariable analyses the strongest
      risk factors for later injecting were always having lived with a relative or
      family friend (not always a parent) and in care/adopted/foster home at any point
      [odds ratio (OR) = 2.66, 95% confidence interval (CI): 1.02-6.92 and OR = 2.17,
      95% CI: 0.91-5.17, respectively], experienced violence from parent or carer (OR =
      2.06, 95% CI: 1.26, 3.38) and early evidence of conduct problems [ever excluded
      from school (OR = 2.73, 95% CI: 1.68, 4.45); childhood criminality (ever arrested
      by police pre-adult OR = 3.05, 95% CI: 1.90, 4.89, ever been in borstal/young
      offenders/list D school OR = 4.70, 95% CI: 2.02, 10.94)]. After adjustment for
      family structure and conduct problems, sexual victimization was associated weakly
      with injecting onset (OR = 1.29, 95% CI: 0.76-2.19). More than 70% of injection
      drug use onset appeared attributable to the risk factors identified. CONCLUSIONS:
      Injection drug use in adults is associated strongly with prior childhood
      adversity, in particular not living with both parents and early conduct problems.
      Prevention initiatives should also consider these risk factors.

PMID- 23163302
TI  - Poaching risks in community-based natural resource management.
AB  - Poaching can disrupt wildlife-management efforts in community-based natural
      resource management systems. Monitoring, estimating, and acquiring data on
      poaching is difficult. We used local-stakeholder knowledge and poaching records
      to rank and map the risk of poaching incidents in 2 areas where natural resources
      are managed by community members in Caprivi, Namibia. We mapped local stakeholder
      perceptions of the risk of poaching, risk of wildlife damage to livelihoods, and
      wildlife distribution and compared these maps with spatially explicit records of
      poaching events. Recorded poaching events and stakeholder perceptions of where
      poaching occurred were not spatially correlated. However, the locations of
      documented poaching events were spatially correlated with areas that stakeholders
      perceived wildlife as a threat to their livelihoods. This result suggests
      poaching occurred in response to wildlife damage occurred. Local stakeholders
      thought that wildlife populations were at high risk of being poached and that
      poaching occurred where there was abundant wildlife. These findings suggest
      stakeholders were concerned about wildlife resources in their community and
      indicate a need for integrated and continued monitoring of poaching activities
      and further interventions at the wildlife-agricultural interface. Involving
      stakeholders in the assessment of poaching risks promotes their participation in
      local conservation efforts, a central tenet of community-based management. We
      considered stakeholders poaching informants, rather than suspects, and our
      technique was spatially explicit. Different strategies to reduce poaching are
      likely needed in different areas. For example, interventions that reduce human
      wildlife conflict may be required in residential areas, and increased and
      targeted patrolling may be required in more remote areas. Stakeholder-generated
      maps of human-wildlife interactions may be a valuable enforcement and
      intervention support tool.

PMID- 23163303
TI  - Predicting post-discharge death or readmission: deterioration of model
      performance in population having multiple admissions per patient.
AB  - BACKGROUND: To avoid biased estimates of standard errors in regression models,
      statisticians commonly limit the analytical dataset to one observation per
      patient. OBJECTIVE: Measure and explain changes in model performance when a model
      predicting 30-day risk of death or urgent readmission (derived on a dataset
      having one hospitalization per patient) was applied to all hospitalizations for
      study patients. METHODS: Using administrative data from Ontario, we identified
      all hospitalizations of 499,996 patients between 2004 and 2009. We calculated the
      expected risk for 30-day death or urgent readmission using a validated model. The
      observed-to-expected ratio was determined after categorizing patients into
      quintiles of rates for hospitalization, emergent hospitalizations, hospital day
      and total diagnostic risk score. RESULTS: Study patients had a total of 858,410
      hospitalizations. Compared with a dataset having one hospitalization per patient,
      model performance declined significantly when applied to all hospitalizations [c
      statistic decreased from 0.768 to 0.730; the observed-to-expected ratio increased
      from 0.998 (95% confidence interval 0.977-0.999) to 1.305 (1.297-1.313)]. Model
      deterioration was most pronounced in patients with higher hospital utilization,
      with the observed-to-expected ratio increasing to 1.67 in the highest quintile of
      emergent hospitalization rates. CONCLUSIONS: The accuracy of predicting 30-day
      death or urgent readmission decreased significantly when the unit of analysis
      changed from the patient to the hospitalization. Patients with heavy hospital
      utilization likely have characteristics, not adequately captured in the model,
      that increase the risk of death or urgent readmission after discharge from
      hospital. Adequately capturing the characteristics of such high-end hospital
      users may improve readmission models.

PMID- 23163304
TI  - Immunomodulatory/anti-inflammatory effects of Baccharis dracunculifolia leaves.
AB  - A possible immunomodulatory/anti-inflammatory effect of Baccharis dracunculifolia
      (Bd) and its major compound--caffeic acid (Ca)--on cytokines production (IL
      1beta, IL-6 and IL-10) by murine macrophages was investigated. Cells were
      incubated with Bd and Ca, and the inhibitory concentrations were tested before or
      after macrophages challenge with LPS. Bd and Ca stimulated IL-1beta and inhibited
      IL-6 and IL-10 production. In LPS-challenge protocols, Bd prevented LPS action
      either before or after LPS challenge, whereas Ca prevented LPS effects only after
      LPS addition. Bd modulatory action on cytokines production may be at least in
      part mediated by Ca, since it has been shown to inhibit the transcription factor
      NF-kappaB. Further studies are still needed to evaluate Bd efficacy in
      inflammatory diseases, in order to explore its antiinflammatory activity in vivo.

PMID- 23163305
TI  - The effect of post length and core material on root fracture with respect to
      different post materials.
AB  - OBJECTIVE: The aim of this study was to evaluate the effect of different core
      materials and post length on the fracture strength of different posts (CAD/CAM
      zirconia post (ZR post)) and an individually formed glass fiber reinforced
      composite post (FRC post). MATERIALS AND METHODS: One hundred maxillary central
      incisors received endodontic treatment and were divided into two groups according
      to the post length: (1) 10 mm in length and (2) 15 mm in length (n = 50/per
      group). Then the specimens were randomly assigned into five sub-groups (n =
      10/per group) as follows: One-piece milled zirconia post and core (group Zr),
      zirconia post with resin core (Biscore, Bisco) (group Zr/R), zirconia post with
      resin composite core (Admira, Voco) (group Zr/RC), FRC post with resin core
      (group F/R) and FRC post with resin composite core (group F/RC). The posts were
      cemented with a self-adhesive luting agent according to the manufacturer's
      instructions by using endo tips and light-cured for 40 s using a halogen light
      curing unit. Metal crowns were made for each specimen, cemented and loaded to
      failure. Fracture loads (N) and modes of failure were recorded. The data were
      analyzed using three-way analysis of variance (ANOVA) followed by Tukey's post
      hoc test (p < 0.001). RESULTS: Fracture strength of roots was significantly
      affected by the type of post material (p < 0.05) and post length (p < 0.05), but
      not by the type of core materials used (p = 0.078). CONCLUSION: Longer zirconia
      posts with zirconia- or resin-based cores can be recommended as an alternative to
      FRC posts with resin-based cores. The fracture patterns observed in teeth
      restored with fiber posts were more favorable than teeth restored with zirconia
      posts. Clinical significance. A higher restoring success rate can be achieved by
      fiber posts rather than zirconia posts, since the failure mode for these posts
      would be restorable. Additionally, post length is a more critical factor in teeth
      restored with one-piece milled zirconia posts than in those restored with fiber
      posts.

PMID- 23163306
TI  - Soft-tissue profile characteristics in children with beta thalassaemia major.
AB  - OBJECTIVES: To compare soft-tissue profile characteristics of patients with beta
      thalassaemia major (BTM) with a group of non-thalasseamic subjects with a similar
      skeletal pattern. SUBJECTS AND METHODS: The material for this cross-sectional
      retrospective study consisted of lateral cephalograms of 40 BTM patients (23
      males, 17 females, aged 9.5 +/- 0.97 years). These were compared with lateral
      cephalograms of a control group of 40 non-thalasseamic subjects (23 males, 17
      females, aged 11.0 +/- 0.87 years) who had similarities with the study group in
      the following cephalometric variables: SNA ( degrees ), SNB ( degrees ), ANB (
      degrees ) and anterior face height (N-Me). Overall, 22 linear and angular soft
      tissue cephalometric variables were measured. RESULTS: Horizontal soft-tissue
      measurements, except for the thickness at B point (B-B'), were larger relative to
      non-thalasseamic subjects; particularly showing a statistically larger mean
      values for the following variables: soft-tissue thickness at Pronasale (ANS-Prn,
      p < 0.01), Subnasale (ANS-Sn, p < 0.01), point A (A-A', p < 0.01) and at the
      Pogonion point (Pg-Pg', p < 0.05). Compared to controls, BTM patients showed
      significantly larger (p < 0.05) mean values for the anterior nose length (Prn
      Prn', p < 0.01) and lower nose height (Prn-Sn, p < 0.05). Variables that
      represented the lip profile, including the nasolabial angle, did not
      significantly differ from controls. The average values for the mid-face (N-ANS),
      posterior face height (S-Go) and the inclination of maxillary incisors to the SN
      plane were significantly larger (p < 0.01) in BTM patients. CONCLUSION: The soft
      tissue profile differences in BTM patients may have implications for their future
      orthodontic or orthognathic management. Future studies can investigate the 3D
      soft-tissue changes and the possible contributing factors.

PMID- 23163307
TI  - Psychometric evaluation of a Swedish version of the Functional Outcomes of Sleep
      Questionnaire, FOSQ.
AB  - OBJECTIVE: The Functional Outcomes of Sleep Questionnaire, FOSQ, is a self
      administered 30 item questionnaire, designed to assess the impact of disorders of
      excessive sleepiness on activities of daily living. The aim was to evaluate the
      psychometric properties of a Swedish translation of the English original.
      MATERIALS AND METHODS: A Swedish version of the FOSQ was answered by 75
      consecutive patients, diagnosed with obstructive sleep apnea syndrome and in need
      of treatment. The Short Form Health Survey (SF-36) and Epworth Sleepiness Scale
      (ESS) were also answered at the same time to evaluate validity. The first 25
      patients answered the FOSQ a second time, 3 weeks later, to assess reliability.
      RESULTS: The test-re-test reliability and intra-class correlation of the
      different sub-scales in the FOSQ varied between 0.71-0.92 and was 0.92 for the
      total scale, all statistically significant. Cronbach's alpha, calculated as a
      measure of internal consistency, varied between 0.84-0.92 for FOSQ sub-scales and
      was 0.96 for the total score. Statistically significant correlations between FOSQ
      sub-scales and the eight sub-scales in the SF-36 supported the validity.
      Discriminant validity, calculated by splitting responders with high and low ESS
      scores, revealed that FOSQs scores differed significantly between the groups.
      CONCLUSIONS: The results suggest that the Swedish version of the FOSQ has
      psychometric qualities in line with the original. It might, therefore, be a
      potentially useful, reliable and valid instrument for clinicians and researchers
      when measuring variables related to quality-of-life in sleep disorders in this
      language area.

PMID- 23163309
TI  - Stephen F. Lowry: handprints in our hearts.

PMID- 23163310
TI  - Epinephrine, cortisol, endotoxin, nutrition, and the neutrophil.
AB  - BACKGROUND: Neutrophil dysfunction has been documented after injury in animals
      and human beings. This review evaluates the relative effects of the hormonal and
      endotoxin response to injury on immune resistance. METHOD: Review of the
      pertinent English-language literature. RESULTS: In volunteers given total
      parenteral nutrition, neutrophils demonstrate a robust response to leukotriene B4
      but none to zymosan/activated serum or the bacterial metabolite formyl-methionyl
      leucyl-phenylalanine (FMLP). This finding suggests subclinical exposure to
      activated complement and FMLP that does not occur during enteral feeding.
      Additional evidence of neutrophil activation is the release of lactoferrin to the
      same degree with the two routes of feeding. When normal volunteers are challenged
      with endotoxin, uniform impairment of the neutrophil response to chemotactic
      stimuli except LTB4 is demonstrated. Epinephrine increases the total circulating
      neutrophil pool for a few hours, whereas when cortisol is administered, the
      neutrophil counts continue to increase through 6 h. A combined epinephrine and
      cortisol infusion extends the half-life of neutrophils. The role of genomic and
      central nervous system control through the vagus nerve also is reviewed.
      CONCLUSION: Normal volunteers have provided insight into the stress response to
      infection that is understood only partially.

PMID- 23163311
TI  - Isolation of Clostridium difficile from peritoneal fluid.

PMID- 23163312
TI  - Enhanced sampling molecular dynamics identifies PrP(Sc) structures harboring a C
      terminal beta-core.
AB  - We perform a replica exchange molecular dynamics simulation corresponding to a
      2.8 MUs total time for the extensive enhanced sampling of the conformational
      space of the C-terminal part (residues 124-226) of the mouse prion protein (PrP);
      1.3% of the conformations sampled display a high level of beta-structure (>=19
      residues), allowing the assessment of beta-propensities along the sequence and
      highlighting the most structurally labile hot spots. A clustering algorithm is
      applied to sort the structures of this pool according to their fold. Ten beta
      rich folds are thus defined and analyzed with regard to their topology,
      accumulation temperatures, and structural characteristics. In contrast to the so
      called spiral and beta-helix models suggesting that the beta-rich core of the
      scrapie isoform (PrP(Sc)) comprises the N-terminal tail and part of the C
      terminal domain up to helix 1 (H1), we present putative structural models for
      monomeric precursors of PrP(Sc) and PrP beta-oligomers that are characterized by
      a C-terminal beta-rich core, in agreement with the suggestions of a series of
      recent experiments.

PMID- 23163313
TI  - Laparoscopic adjustable gastric banding vs standard medical management in obese
      patients with type 2 diabetes: a budget impact analysis in the UK.
AB  - OBJECTIVE: To evaluate the financial consequences of using laparoscopic
      adjustable gastric banding (LAGB) in place of standard medical management (SMM)
      in obese patients with type 2 diabetes from a UK healthcare payer perspective.
      DESIGN AND METHODS: A budget impact model was constructed to evaluate the
      budgetary implications of LAGB in obese patients with type 2 diabetes in the UK.
      For patients undergoing LAGB, the model captured pre-, peri-, and post-operative
      costs including consultations with physicians, psychologists, nurses, and
      dieticians, the cost of surgery, and costs associated with post-surgical
      complications. The model also captured costs associated with medication for
      diabetes, asthma, hypertension, and hyperlipidemia, costs of diabetes
      complications, sleep apnea, and asthma, and costs of diagnostic tests. The SMM
      arm also captured costs associated with very low calorie diet products. Costs
      were modeled in a simulated UK cohort of 100 obese patients with newly-diagnosed
      diabetes. Future costs were discounted at 3.5% per annum and all costs were
      reported in 2010 pounds sterling. RESULTS: Over the 5-year time horizon, the
      cohort of 100 patients who underwent LAGB incurred costs L91,287 lower than an
      equivalent cohort receiving SMM (L818,668 and L909,955, respectively). Costs of
      surgery and post-surgical complications (L254,000 and L40,981, respectively) were
      more than offset by savings arising from reduced diabetes, asthma, and sleep
      apnea medication costs, reduced incidence of diabetes complications, and fewer
      healthcare professional contacts. Sensitivity analysis (SA) showed that the model
      was most sensitive to assumptions around diabetes medication use, although none
      of the SA findings showed LAGB to be more costly than SMM. LIMITATIONS: In order
      to capture the diverse resource use and medical care costs arising in obese
      patients with type 2 diabetes, the analysis made use of a range of heterogeneous
      data sources. While the vast majority of data were applicable to obese patients
      with recently-diagnosed diabetes in the UK setting, some surrogate data (e.g.
      from different geographies) were used in cases where data in the target
      population were unavailable. Additionally, given the largely uncharacterized long
      term risk profile in patients with remission of type 2 diabetes, remission was
      captured using a transparent and highly conservative approach. CONCLUSIONS: Based
      on the findings of the present analysis, the high initial costs of performing
      LAGB are offset within 5 years after surgery when compared with SMM in a
      population of obese patients with type 2 diabetes. The high up-front costs
      associated with surgery should not therefore be a barrier to its reimbursement in
      this patient group.

PMID- 23163314
TI  - Occupational injuries, duty status, and factors associated with injuries among
      firefighters.
AB  - The aim of this study was to assess the type of occupational injuries, duty
      status, and factors associated with injuries among firefighters. A total of 437
      firefighters from three U.S. states participated in an Internet-based survey.
      Approximately 66% of firefighters experienced occupational injuries and 56%
      reported multiple injuries. The most commonly reported injuries were muscle
      strains and sprains (74%), extremity injuries (60%), back injuries (54%), and
      burns (28%). A significant number of firefighters reported no duty (58%) or
      modified duty (46%). Firefighters with more than 17 years in fire services were
      more likely to report injuries (odds ratio [OR] = 2.96; 95% confidence interval
      [CI] = 1.92-4.58) and multiple injuries (OR = 2.47; 95% CI = 1.49-4.10).
      Hispanics (OR = 0.34; 95% CI = 0.15-0.76) and those with stronger organizational
      commitments (OR = 0.54; 95% CI = 0.35-0.84) were less likely to report injuries.
      Several factors were associated with injuries. These factors should be
      incorporated into interventions to reduce occupational injuries.

PMID- 23163315
TI  - EPR and circular dichroism solution studies on the interactions of bovine serum
      albumin with ionic surfactants and beta-cyclodextrin.
AB  - The interactions of bovine serum albumin (BSA) with ionic surfactants (sodium
      dodecyl sulfate, SDS, and cetyltrimethylammonium bromide, CTAB) and beta
      cyclodextrin (beta-CD) have been investigated by electron paramagnetic resonance
      (EPR) and circular dichroism measurements. The spin probe selected to report on
      the interaction of albumin with surfactants and/or beta-CD was 4-N,N-dimethyl
      hexadecyl ammonium-2,2,6,6-tetramethylpiperidine-1-oxyl iodide (CAT16), on
      account of (a) its balance between electrostatic and hydrophobic character and
      (b) the ability of BSA to form complexes with various organic molecules. The
      distribution of the spin probe among different environments in solutions
      containing only BSA was confirmed by the existence of two components in the EPR
      spectra: one revealing a restricted mobility of the spin probe, attributed to the
      protein-spin probe complex, and another one showing free movement, attributed to
      the spin probe in solution. The presence of surfactants and/or beta-CD alters the
      distribution of CAT16 between various compartments in each system. Formation of
      protein aggregates as a result of thermal denaturation was evidenced by the
      appearance of an immobilized component in the EPR spectrum. This component is not
      present in the EPR spectra of CAT16 in protein/surfactant or protein/cyclodextrin
      solutions. Circular dichroism spectra of BSA provided information about changes
      in the secondary structure of the protein induced by the presence of surfactants
      and/or cyclodextrin in solution. The results demonstrate that beta-CD hinders the
      interaction between the employed surfactants and the protein. The cationic
      surfactant (CTAB) induces changes in protein conformation at a lower
      concentration compared to the anionic surfactant (SDS).

PMID- 23163317
TI  - Bacterial reduction as means for colonic drug delivery: can other chemical groups
      provide an alternative to the azo bond?
AB  - We compared the rate of colonic bacterial reduction of disulfide and nitro bonds
      to that of an azo counterpart. The disulfide and nitro reduction rates are
      comparable to that of azo having a similar molecular structure. We further
      explored QSAR of bacterial reduction of different nitro compounds giving a
      Hammett correlation with rho=0.553, R2=0.97. We conclude that disulfide and nitro
      compounds have an unexploited potential for use in prodrugs and drug delivery
      systems targeted to the colon.

PMID- 23163316
TI  - Stratified approaches to the treatment of asthma.
AB  - While asthma is a chronic inflammatory disorder that is managed with inhaled
      controller and reliever drugs, there remains a large unmet need at the severe end
      of the disease spectrum. Here, a novel stratified approach to its treatment is
      reviewed, based upon identification of causal pathways, with a focus on
      biologics. A systematic search of the literature was made using Medline, and
      publications were selected on the basis of their relevance to the topic. Despite
      strong preclinical data for many of the more recently identified asthma targets,
      especially those relating to the T-helper 2 allergic pathway, clinical trials
      with specific biologics in moderate to severe asthma as a group have been
      disappointing. However, subgroup analyses based upon pathway-specific biomarkers
      suggest specific endotypes that are responsive. Application of hypothesis-free
      analytical approaches (the 'omics') to well-defined phenotypes is leading to the
      stratification of asthma along causal pathways. Refinement of this approach is
      likely to be the future for diagnosing and treating this group of diseases, as
      well as helping to define new causal pathways. The identification of responders
      and nonresponders to targeted asthma treatments provides a new way of looking at
      asthma diagnosis and management, especially with biologics that are costly. The
      identification of novel biomarkers linked to well-phenotyped patients provides a
      stratified approach to disease management beyond simple disease severity and
      involving causal pathways. In order to achieve this effectively, a closer
      interaction will be required between industry (therapeutic and diagnostic),
      academia and health workers. 

PMID- 23163318
TI  - The tower of Babel: survey on concepts and terminology in electrical status
      epilepticus in sleep and continuous spikes and waves during sleep in North
      America.
AB  - PURPOSE: The terms "electrical status epilepticus during sleep (ESES)" and
      "continuous spikes and waves during sleep (CSWS)" have been used interchangeably
      when referring to related but different concepts. In addition, the quantification
      of epileptiform activity has not been standardized, and different approaches to
      quantification have been used. The aim of this study was to evaluate the extent
      to which pediatric neurologists and epileptologists use a homogeneous terminology
      and conceptualization in CSWS and ESES and to characterize the current
      understanding of these conditions. METHODS: A survey addressing the use of
      terminology in "ESES" and "CSWS" and the understanding of related concepts was
      distributed online to all members of the Child Neurology Society and the American
      Epilepsy Society mailing lists. Surveys were self-administered and collected
      using an online survey website (http://www.surveymonkey.com). KEY FINDINGS:   Two
      hundred nineteen surveys were completed, 137 from the Child Neurology Society
      mailing list and 82 from the American Epilepsy Society mailing list. ESES and
      CSWS were considered synonymous by 117 respondents, not synonymous by 61, 21
      respondents did not know, and 20 did not respond. Most respondents (63.1%)
      considered CSWS as a devastating epileptic encephalopathy with severe sequelae
      even if treated correctly, but 25.1% of respondents indicated that it does not
      leave sequelae if epilepsy was treated early and another 11.8% noted that
      cognitive difficulties resolved with age. Cognitive and/or language regression
      were considered mandatory for the diagnosis of CSWS by only 27% of the
      respondents. The diagnosis of CSWS was based on electroencephalography (EEG)
      assessment alone by 31% of respondents. Respondents used different methods for
      calculation of the epileptiform activity, different EEG samples for calculation,
      and considered differently the lateralized epileptiform activity. The cut-off
      values for percentage of the sleep record occupied by spike-waves were variable
      depending on the respondent. There was no agreement on whether these cutoff
      values were mandatory for the diagnosis of ESES and CSWS. SIGNIFICANCE:   Our
      data show that the professionals caring for children with ESES and CSWS in North
      America use the terms, concepts, and defining features heterogeneously. The lack
      of a common language may complicate communication among clinicians and jeopardize
      research in this field. We anticipate that our data will fuel the development of
      much needed common terminology and conceptualization of ESES and CSWS.

PMID- 23163320
TI  - Household light makes global heat: high black carbon emissions from kerosene wick
      lamps.
AB  - Kerosene-fueled wick lamps used in millions of developing-country households are
      a significant but overlooked source of black carbon (BC) emissions. We present
      new laboratory and field measurements showing that 7-9% of kerosene consumed by
      widely used simple wick lamps is converted to carbonaceous particulate matter
      that is nearly pure BC. These high emission factors increase previous BC emission
      estimates from kerosene by 20-fold, to 270 Gg/year (90% uncertainty bounds: 110,
      590 Gg/year). Aerosol climate forcing on atmosphere and snow from this source is
      estimated at 22 mW/m2 (8, 48 mW/m2), or 7% of BC forcing by all other energy
      related sources. Kerosene lamps have affordable alternatives that pose few clear
      adoption barriers and would provide immediate benefit to user welfare. The net
      effect on climate is definitively positive forcing as coemitted organic carbon is
      low. No other major BC source has such readily available alternatives, definitive
      climate forcing effects, and cobenefits. Replacement of kerosene-fueled wick
      lamps deserves strong consideration for programs that target short-lived climate
      forcers.

PMID- 23163321
TI  - Regulation of Toll-like receptor signaling pathways in innate immune responses.
AB  - Toll-like receptors (TLRs) are critical pattern recognition receptors (PRRs) that
      recognize pathogen-associated molecular patterns (PAMPs), which are conserved and
      specific molecular "signatures" expressed by pathogens. TLR ligation triggers
      distinct but shared signaling pathways that lead to effector mechanisms in innate
      immune responses. TLR specificity and activation are strictly and finely tuned at
      multiple levels of various signal transduction pathways, resulting in complex
      signaling platforms. Many molecules, ranging from membrane and cytosol to
      nuclear, contribute to TLR ligand discrimination or receptor signaling and play
      different roles in the regulation of TLR responses via different mechanisms, such
      as cross-regulation, protein modification, helper cofactors, and
      posttranscriptional and epigenetic regulation. Herein, we summarize the most
      recent literature that provides new insight into regulation of TLR signaling
      triggered innate immune responses. A greater understanding of the mechanisms
      underlying the control of TLR signaling may provide new targets for therapeutic
      intervention for infections and inflammatory diseases.

PMID- 23163319
TI  - Cryptic speciation in the field vole: a multilocus approach confirms three highly
      divergent lineages in Eurasia.
AB  - Species are generally described from morphological features, but there is growing
      recognition of sister forms that show substantial genetic differentiation without
      obvious morphological variation and may therefore be considered 'cryptic
      species'. Here, we investigate the field vole (Microtus agrestis), a Eurasian
      mammal with little apparent morphological differentiation but which, on the basis
      of previous sex-linked nuclear and mitochondrial DNA (mtDNA) analyses, is
      subdivided into a Northern and a Southern lineage, sufficiently divergent that
      they may represent two cryptic species. These earlier studies also provided
      limited evidence for two major mtDNA lineages within Iberia. In our present
      study, we extend these findings through a multilocus approach. We sampled 163
      individuals from 46 localities, mainly in Iberia, and sequenced seven loci,
      maternally, paternally and biparentally inherited. Our results show that the
      mtDNA lineage identified in Portugal is indeed a distinct third lineage on the
      basis of other markers as well. In fact, multilocus coalescent-based methods
      clearly support three separate evolutionary units that may represent cryptic
      species: Northern, Southern and Portuguese. Divergence among these units was
      inferred to have occurred during the last glacial period; the Portuguese lineage
      split occurred first (estimated at c. 70 000 bp), and the Northern and Southern
      lineages separated at around the last glacial maximum (estimated at c. 18 500
      bp). Such recent formation of evolutionary units that might be considered species
      has repercussions in terms of understanding evolutionary processes and the
      diversity of small mammals in a European context.

PMID- 23163322
TI  - Blood pressure and metabolic efficacy of fixed-dose combination of perindopril
      and indapamide in everyday practice.
AB  - The aim of the PICASSO study was to evaluate the efficacy and safety of fixed
      dose perindopril 10 mg/indapamide 2.5 mg in everyday medical practice. In this 3
      month, open-label, observational study, outpatients with primary hypertension who
      did not reach the blood pressure goal (< 140/90 mmHg) with antihypertensive
      treatment were enrolled if their treating physician had planned, as part of their
      ongoing therapy, to switch them to fixed-dose perindopril 10 mg/indapamide 2.5
      mg. Blood pressure, heart rate, and metabolic parameters and - optionally -
      ambulatory blood pressure were measured. Data from 9257 patients were evaluated.
      Over the course of 3 months, mean blood pressure decreased from 159/93 mmHg to
      132/80 mmHg (p < 0.001) and heart rate decreased from 79 to 73 beats/min (p <
      0.001). The target blood pressure was reached by 72.7% of patients. Reductions in
      total cholesterol, low-density lipoprotein-cholesterol (LDL-c), triglycerides,
      fasting glucose and uric acid levels were clinically significant. Blood levels of
      high-density lipoprotein-cholesterol (HDL-c), sodium and potassium remained
      unchanged. Beneficial changes in metabolic parameters were primarily attributed
      to the reduction in therapy with drugs with unfavourable metabolic profiles
      (thiazides and beta-blockers). Perindopril/indapamide is an effective and safe
      antihypertensive treatment in everyday medical practice.

PMID- 23163324
TI  - Postharvest grape infection of Botrytis cinerea and its interactions with other
      moulds under withering conditions to produce noble-rotten grapes.
AB  - AIMS: To investigate the interactions between Botrytis cinerea and other moulds
      during grape withering and postharvest infection to obtain noble-rotten grapes.
      METHODS AND RESULTS: Strains of Botrytis cinerea, Penicillium expansum,
      Penicillium crustosum, Aspergillus niger, Fusarium verticilloides and Alternaria
      alternata, isolated from naturally withered grapes and identified by molecular
      tools, were used to infect Garganega and Corvina grapes. Individually sterilized
      berries were infected by a single inoculation of each strain or a simultaneous
      inoculation of B. cinerea together with one of each of the other moulds.
      Withering kinetics, glycerol, gluconic acid, total polyphenols, total
      anthocyanins and laccase activity greatly varied among each strain and also in
      respect to untreated berries. Successful noble rot settlement was ascertained by
      an additional infection assay carried out on nonsterilized berries. CONCLUSIONS:
      The suitability of inducing noble rot infection during grape withering and the
      improvement of the health of noble-rotten grapes have been demonstrated.
      SIGNIFICANCE AND IMPACT OF THE STUDY: This study provides insights on the effects
      of mould interactions on withered grape quality. Implementing noble rot induction
      by postharvest infection in winery drying fruit rooms to standardize the level of
      grape botrytization is encouraged.

PMID- 23163325
TI  - Natural selection. V. How to read the fundamental equations of evolutionary
      change in terms of information theory.
AB  - The equations of evolutionary change by natural selection are commonly expressed
      in statistical terms. Fisher's fundamental theorem emphasizes the variance in
      fitness. Quantitative genetics expresses selection with covariances and
      regressions. Population genetic equations depend on genetic variances. How can we
      read those statistical expressions with respect to the meaning of natural
      selection? One possibility is to relate the statistical expressions to the amount
      of information that populations accumulate by selection. However, the connection
      between selection and information theory has never been compelling. Here, I show
      the correct relations between statistical expressions for selection and
      information theory expressions for selection. Those relations link selection to
      the fundamental concepts of entropy and information in the theories of physics,
      statistics and communication. We can now read the equations of selection in terms
      of their natural meaning. Selection causes populations to accumulate information
      about the environment.

PMID- 23163326
TI  - Sexual selection in fungi.
AB  - The significance of sexual selection, the component of natural selection
      associated with variation in mating success, is well established for the
      evolution of animals and plants, but not for the evolution of fungi. Even though
      fungi do not have separate sexes, most filamentous fungi mate in a hermaphroditic
      fashion, with distinct sex roles, that is, investment in large gametes (female
      role) and fertilization by other small gametes (male role). Fungi compete to
      fertilize, analogous to 'male-male' competition, whereas they can be selective
      when being fertilized, analogous to female choice. Mating types, which determine
      genetic compatibility among fungal gametes, are important for sexual selection in
      two respects. First, genes at the mating-type loci regulate different aspects of
      mating and thus can be subject to sexual selection. Second, for sexual selection,
      not only the two sexes (or sex roles) but also the mating types can form the
      classes, the members of which compete for access to members of the other class.
      This is significant if mating-type gene products are costly, thus signalling
      genetic quality according to Zahavi's handicap principle. We propose that sexual
      selection explains various fungal characteristics such as the observed high
      redundancy of pheromones at the B mating-type locus of Agaricomycotina, the
      occurrence of multiple types of spores in Ascomycotina or the strong pheromone
      signalling in yeasts. Furthermore, we argue that fungi are good model systems to
      experimentally study fundamental aspects of sexual selection, due to their fast
      generation times and high diversity of life cycles and mating systems.

PMID- 23163327
TI  - The relative importance of genetic and nongenetic inheritance in relation to
      trait plasticity in Callosobruchus maculatus.
AB  - A trait's response to natural selection will reflect the nature of the
      inheritance mechanisms that mediate the transmission of variation across
      generations. The relative importance of genetic and nongenetic mechanisms of
      inheritance is predicted to be related to the degree of trait plasticity, with
      nongenetic inheritance playing a greater role in the cross-generational
      transmission of more plastic traits. However, this prediction has never been
      tested. We investigated the influence of genetic effects and nongenetic parental
      effects in two morphological traits differing in degree of plasticity by
      manipulating larval diet quality within a cross-generational split-brood
      experiment using the seed beetle Callososbuchus maculatus. In line with
      predictions, we found that the more plastic trait (elytron length) is strongly
      influenced by both maternal and paternal effects whereas genetic variance is
      undetectable. In contrast, the less plastic trait (first abdominal sternite
      length) is not influenced by parental effects but exhibits abundant genetic
      variance. Our findings support the hypothesis that environment-dependent parental
      effects may play a particularly important role in highly plastic traits and
      thereby affect the evolutionary response of such traits.

PMID- 23163328
TI  - Rapid diversification of Tragopogon and ecological associates in Eurasia.
AB  - Tragopogon comprises approximately 150 described species distributed throughout
      Eurasia from Ireland and the UK to India and China with a few species in North
      Africa. Most of the species diversity is found in Eastern Europe to Western Asia.
      Previous phylogenetic analyses identified several major clades, generally
      corresponding to recognized taxonomic sections, although relationships both among
      these clades and among species within clades remain largely unresolved. These
      patterns are consistent with rapid diversification following the origin of
      Tragopogon, and this study addresses the timing and rate of diversification in
      Tragopogon. Using BEAST to simultaneously estimate a phylogeny and divergence
      times, we estimate the age of a major split and subsequent rapid divergence
      within Tragopogon to be ~2.6 Ma (and 1.7-5.4 Ma using various clock estimates).
      Based on the age estimates obtained with BEAST (HPD 1.7-5.4 Ma) for the origin of
      crown group Tragopogon and 200 estimated species (to accommodate a large number
      of cryptic species), the diversification rate of Tragopogon is approximately 0.84
      2.71 species/Myr for the crown group, assuming low levels of extinction. This
      estimate is comparable in rate to a rapid Eurasian radiation in Dianthus (0.66
      3.89 species/Myr), which occurs in the same or similar habitats. Using available
      data, we show that subclades of various plant taxa that occur in the same semi
      arid habitats of Eurasia also represent rapid radiations occurring during roughly
      the same window of time (1.7-5.4 Ma), suggesting similar causal events. However,
      not all species-rich plant genera from the same habitats diverged at the same
      time, or at the same tempo. Radiations of several other clades in this same
      habitat (e.g. Campanula, Knautia, Scabiosa) occurred at earlier dates (45-4.28
      Ma). Existing phylogenetic data and diversification estimates therefore indicate
      that, although some elements of these semi-arid communities radiated during the
      Plio-Pleistocene period, other clades sharing the same habitat appear to have
      diversified earlier.

PMID- 23163329
TI  - The heritable basis and cost of colour plasticity in coastrange sculpins.
AB  - Both genetic and plastic traits contribute to adaptation in novel environments.
      Phenotypic plasticity can facilitate adaptation by allowing for existence in a
      wider range of conditions and a faster response to environmental change than gene
      based selection. Coastrange sculpins (Cottus aleuticus) colonize new and variable
      streams arising in the wake of receding glaciers in south-east Alaska, and
      substrate-matching plasticity may enhance colonization success by reducing
      detection by visual predators. As part of a long-term study of the fitness
      consequences of colour plasticity and its capacity to respond to both positive
      and negative selection, we investigated whether it is heritable and costly. We
      raised full-sib broods of sculpins in the laboratory: one half of each brood was
      raised in white containers, the other half in black. After 4 months, we digitally
      analysed their colour and found significant but weak heritability in both
      baseline colour and colour plasticity. To investigate the cost of colour
      plasticity, we compared the growth and mortality rates of juvenile sculpins
      reared under constant substrate colours to those reared on substrates that
      changed colour frequently, and compared growth rates among sculpin that differed
      in their colour change ability. We found evidence of small costs of plasticity,
      consistent with other studies of natural populations. Evidence of heritable
      genetic variation for plasticity and small costs to its maintenance and
      expression contributes to explanations of how plasticity is variable and
      persistent among wild populations and underscores its ability to respond both
      positively and negatively to selection in variable habitats.

PMID- 23163330
TI  - Comparison of presenting features and three-year disease course in Turkish
      patients with Behcet uveitis who presented in the early 1990s and the early
      2000s.
AB  - PURPOSE: To compare Behcet uveitis patients who presented in the 1990s and 2000s.
      METHODS: Records of 170 patients seen in 1990-1994 and 258 patients seen in 2000
      2004 were reviewed. Presenting features were analyzed in the whole cohort.
      Uveitis attacks, vision, complications, and immunomodulatory treatment (IMT) were
      compared in patients with 3-year follow-up. RESULTS: Posterior segment
      involvement was less common, visual acuity was better, and more patients received
      IMT before referral in the 2000s. Follow-up revealed no significant difference in
      number of uveitis attacks in the first 3 years. Less eyes lost useful vision, no
      patient became legally blind, and fewer severe ocular complications occurred in
      the 2000s. IMT was started within 3 months in more patients and interferon alfa
      2a was used only in the latter study period. CONCLUSIONS: The findings suggest a
      milder disease at referral, lower rate of severe complications, and a better 3
      year visual outcome in patients who presented in the early 2000s.

PMID- 23163332
TI  - Property-based optimization of hydroxamate-based gamma-lactam HDAC inhibitors to
      improve their metabolic stability and pharmacokinetic profiles.
AB  - Hydroxamate-based HDAC inhibitors have promising anticancer activities but
      metabolic instability and poor pharmacokinetics leading to poor in vivo results.
      QSAR and PK studies of HDAC inhibitors showed that a gamma-lactam core and a
      modified cap group, including halo, alkyl, and alkoxy groups with various carbon
      chain linkers, improved HDAC inhibition and metabolic stability. The biological
      properties of the gamma-lactam HDAC inhibitors were evaluated; the compound
      designated 8f had potent anticancer activity and high oral bioavailability.

PMID- 23163331
TI  - Biochemical-, biophysical-, and microarray-based antifungal evaluation of the
      buffer-mediated synthesized nano zinc oxide: an in vivo and in vitro toxicity
      study.
AB  - Here we describe a simple, novel method of zinc oxide nanoparticle (ZNP)
      synthesis and physicochemical characterization. The dose-dependent antifungal
      effect of ZNPs, compared to that of micronized zinc oxide (MZnO), was studied on
      two pathogenic fungi: Aspergillus niger and Fusarium oxysporum. Superoxide
      dismutase (SOD) activity, ascorbate peroxidase activity, catalase activity,
      glutathione reductase (GR) activity, thiol content, lipid peroxidation, and
      proline content in ZNP-treated fungal samples were found to be elevated in
      comparison to the control, which strongly suggested that the antifungal effect of
      ZNPs was due to the generation of reactive oxygen species (ROS). Protein
      carbonylation, another marker of oxidative stress, was also evaluated by the
      dinitrophenyl hydrazine (DNPH) binding assay and Fourier transform infrared
      (FTIR) spectral analysis followed by Western blot and microarray analysis of
      fungal samples to confirm ROS generation by ZNPs. Micrographic studies for the
      morphological analysis of fungal samples (ZNP-treated and a control) exhibited an
      alteration in fungal morphology. The bioavailability of ZNPs on fungal cell was
      confirmed by energy-dispersive X-ray (EDX) analysis followed by high-resolution
      transmission electron microscopy (HR-TEM) and confocal microscopic analysis of
      the fungal samples. In vivo acute oral toxicity, acetylcholine esterase activity,
      and a fertility study using a mice model were also investigated for ZNPs. The
      long-term toxicity of ZNPs through intravenous injection was evaluated and
      compared to that of MZnO. The in vitro comparative toxicity of ZNPs and MZnO was
      evaluated on MRC-5 cells with the help of water-soluble tetrazolium (WST-1) and
      lactate dehydrogenase (LDH) assays. These results suggested that ZNPs could be
      used as an effective fungicide in modern medical and agricultural sciences.

PMID- 23163333
TI  - Introducing the JME special issue on cost-effectiveness analyses.

PMID- 23163335
TI  - A geographic mosaic of evolutionary lineages within the insular endemic newt
      Euproctus montanus.
AB  - Islands are hotspots of biodiversity, with a disproportionately high fraction of
      endemic lineages, often of ancient origin. Nevertheless, intra-island
      phylogeographies are surprisingly scarce, leading to a scanty knowledge about the
      microevolutionary processes induced on island populations by Plio-Pleistocene
      climatic oscillations, and the manner in which these processes contributed to
      shape their current genetic diversity. We investigated the phylogeography,
      historical demography and species distribution models of the Corsican endemic
      newt Euproctus montanus (north-western Mediterranean). As for many island
      endemics, the continuous distribution of E. montanus throughout its range has
      hitherto been considered as evidence for a single large population, a belief that
      also guided the species' categorization for conservation purposes. Instead, we
      found a geographic mosaic of ancient evolutionary lineages, with five main clades
      of likely Pliocene origin (2.6-5.8 My), all but one restricted to northern
      Corsica. Moreover, the copresence between main lineages in the same population
      was limited to a single case. As also suggested by growing literature on intra
      island phylogeographic variation, it seems that the extensive use of simplifying
      assumption on the population structure and historical demography of island
      populations--both in theoretical and applicative studies--should be carefully
      reconsidered, a claim that is well exemplified by the case presented here.

PMID- 23163334
TI  - Onboard measurements of nanoparticles from a SCR-equipped marine diesel engine.
AB  - In this study nanoparticle emissions have been characterized onboard a ship with
      focus on number, size, and volatility. Measurements were conducted on one of the
      ship's four main 12,600 kW medium-speed diesel engines which use low sulfur
      marine residual fuel and have a Selective Catalytic Reduction (SCR) system for
      NO(X) abatement. The particles were measured after the SCR with an engine exhaust
      particle sizer spectrometer (EEPS), giving particle number and mass distributions
      in the size range of 5.6-560 nm. The thermal characteristics of the particles
      were analyzed using a volatility tandem DMA system (VTDMA). A dilution ratio of
      450-520 was used which is similar to the initial real-world dilution. At a stable
      engine load of 75% of the maximum rated power, and after dilution and cooling of
      the exhaust gas, there was a bimodal number size distribution, with a major peak
      at ~10 nm and a smaller peak at around 30-40 nm. The mass distribution peaked
      around 20 nm and at 50-60 nm. The emission factor for particle number, EF(PN),
      for an engine load of 75% in the open-sea was found to be 10.4 +/- 1.6 * 10(16)
      (kg fuel)(-1) and about 50% of the particles by number were found to have a
      nonvolatile core at 250  degrees C. Additionally, 20 nm particles consist of ~40%
      of nonvolatile material by volume (evaporative temperature 250  degrees C), while
      the particles with a particle diameter <10 nm evaporate completely at a
      temperature of 130-150  degrees C. Emission factors for NO(X), CO, and CO(2) for
      an engine load of 75% in the open-sea were determined to 4.06 +/- 0.3 g (kg
      fuel)(-1), 2.15 +/- 0.06 g (kg fuel)(-1), and 3.23 +/- 0.08 kg (kg fuel)(-1),
      respectively. This work contributes to an improved understanding of particle
      emissions from shipping using modern pollution reduction measures such as SCR and
      fuel with low sulfur content.

PMID- 23163336
TI  - Side effects of common acne treatments.
AB  - INTRODUCTION: A variety of acne treatments exist, including topical benzoyl
      peroxide, topical retinoids, topical antibiotics, oral antibiotics, hormonal
      therapy, isotretinoin, and procedural therapies, such as light and laser
      therapies. Although each of these treatment modalities confer various benefits
      for the management of acne, it is important for healthcare providers to be aware
      of their potential side effects, including ones that are most common and most
      serious, so that these medications can be prescribed in a safe manner. AREAS
      COVERED: A systematic literature review was performed to identify publications
      discussing the side effects of the different treatment modalities used for acne
      vulgaris. Acne treatments reviewed included benzoyl peroxide gel, topical
      retinoids, topical antibiotics, oral antibiotics, hormonal therapy, isotretinoin,
      and light/laser treatments. EXPERT OPINION: A comprehensive overview of acne
      treatments' side effects is imperative for healthcare professionals and
      scientists working with and prescribing acne treatments. Side effects to be aware
      of when prescribing range from local irritation with topical treatments to
      systemic side effects including liver function abnormalities and teratogenic side
      effects. The best available options are those that address acne severity while
      minimizing side effects for the patient. Consequently, personalized medicine must
      be strongly emphasized to healthcare providers developing patients' treatment
      plans.

PMID- 23163337
TI  - Genetic requirements for Moraxella catarrhalis growth under iron-limiting
      conditions.
AB  - Iron sequestration by the human host is a first line defence against respiratory
      pathogens like Moraxella catarrhalis, which consequently experiences a period of
      iron starvation during colonization. We determined the genetic requirements for
      M. catarrhalis BBH18 growth during iron starvation using the high-throughput
      genome-wide screening technology genomic array footprinting (GAF). By subjecting
      a large random transposon mutant library to growth under iron-limiting
      conditions, mutants of the MCR_0996-rhlB-yggW operon, rnd, and MCR_0457 were
      negatively selected. Growth experiments using directed mutants confirmed the GAF
      phenotypes with DeltayggW (putative haem-shuttling protein) and DeltaMCR_0457
      (hypothetical protein) most severely attenuated during iron starvation,
      phenotypes which were restored upon genetic complementation of the deleted genes.
      Deletion of yggW resulted in similar attenuated phenotypes in three additional
      strains. Transcriptional profiles of DeltayggW and DeltaMCR_0457 were highly
      altered with 393 and 192 differentially expressed genes respectively. In all five
      mutants, expression of nitrate reductase genes was increased and of nitrite
      reductase decreased, suggesting an impaired aerobic respiration. Alteration of
      iron metabolism may affect nasopharyngeal colonization as adherence of all
      mutants to respiratory tract epithelial cells was attenuated. In conclusion, we
      elucidated the genetic requirements for M. catarrhalis growth during iron
      starvation and characterized the roles of the identified genes in bacterial
      growth and host interaction.

PMID- 23163338
TI  - In silico modeling and experimental evidence of coagulant protein interaction
      with precursors for nanoparticle functionalization.
AB  - The design of novel protein-nanoparticle hybrid systems has applications in many
      fields of science ranging from biomedicine, catalysis, water treatment, etc. The
      main barrier in devising such tool is lack of adequate information or poor
      understanding of protein-ligand chemistry. Here, we establish a new strategy
      based on computational modeling for protein and precursor linkers that can
      decorate the nanoparticles. Moringa oleifera (MO2.1) seed protein that has
      coagulation and antimicrobial properties was used. Superparamagnetic
      nanoparticles (SPION) with precursor ligands were used for the protein-ligand
      interaction studies. The molecular docking studies reveal that there are two
      binding sites, one is located at the core binding site; tetraethoxysilane (TEOS)
      or 3-aminopropyl trimethoxysilane (APTES) binds to this site while the other one
      is located at the side chain residues where trisodium citrate (TSC) or Si60 binds
      to this site. The protein-ligand distance profile analysis explains the
      differences in functional activity of the decorated SPION. Experimentally, TSC
      coated nanoparticles showed higher coagulation activity as compared to TEOS- and
      APTES-coated SPION. To our knowledge, this is the first report on in vitro
      experimental data, which endorses the computational modeling studies as a
      powerful tool to design novel precursors for functionalization of nanomaterials;
      and develop interface hybrid systems for various applications. 

PMID- 23163339
TI  - Reply to comments on 'vascular effects of dietary nitrate (as found in green
      leafy vegetables and beetroot) via the nitrate-nitrite-nitric oxide pathway'.

PMID- 23163340
TI  - Betula pendula Roth leaves: gastroprotective effects of an HPLC-fingerprinted
      methanolic extract.
AB  - In this study, a methanolic extract of Betula pendula leaves (BLE) was
      investigated for its gastroprotective effects against 90% ethanol-induced ulcer
      in rats. Oral pretreatment of rats with BLE (100, 200 and 400 mg kg(- 1))
      significantly reduced the incidence of gastric lesions induced by ethanol
      administration as compared with misoprostol (0.50 mg kg(- 1)). Furthermore, BLE
      inhibited the increase in malondialdehyde (MDA) and prevented depletion of total
      sulhydryl and non-protein sulhydryl groups in rat stomach homogenate when
      compared with ethanol group. With regard to the effect of lipid peroxidation in
      vitro, BLE showed the ability to reduce methyl linoleate autoxidation. Chemical
      characterisation of the main biologically active constituents of BLE was also
      achieved by means of high-performance liquid chromatography with photodiode array
      and mass spectrometry detection, showing the presence of myricetin-3-O
      galactoside, quercetin glycosides, kaempferol glycosides.

PMID- 23163341
TI  - Cardiovascular disease and non-steroidal anti-inflammatory drug prescribing in
      the midst of evolving guidelines.
AB  - RATIONALE, AIMS AND OBJECTIVES: Responding to safety concerns, the American Heart
      Association (AHA) published guidelines for non-steroidal anti-inflammatory drug
      (NSAID) use in patients with pre-existing cardiovascular disease (CVD) during
      2005 and revised them in 2007. In the revision, a stepped approach to pain
      management recommended non-selective NSAIDs over highly selective NSAIDs. This
      research evaluated NSAID prescribing during and after guideline dissemination.
      METHOD: A cross-sectional sample of 8666 adult, community-based practice visits
      with one NSAID prescription representing approximately 305 million visits from
      the National Ambulatory Medical Care Survey (NAMCS) from 2005 to 2010 was
      studied. Multivariable logistic regression controlling for patient, provider and
      visit characteristics assessed the associations between diagnosis of CVD and
      NSAID type prescribed during each calendar year. Visits were stratified by
      arthritis diagnosis to model short-term/intermittent and long-term NSAID use.
      RESULTS: Approximately one-third (36.8%) of visits involving a NSAID prescription
      included at least one of four diagnoses for CVD (i.e. hypertension, congestive
      heart failure, ischaemic heart disease or cerebrovascular disease). Visits
      involving a CVD diagnosis had increased odds of a prescription for celecoxib, a
      highly selective NSAIDs, overall [adjusted odds ratio (AOR) = 1.29, 95%
      confidence interval (CI): 1.06-1.57] and in the subgroup of visits without an
      arthritis diagnosis (AOR = 1.45, 95% CI: 1.11-1.89). Results were not
      statistically significant for visits with an arthritis diagnosis (AOR = 1.10, 95%
      CI: 0.47-2.57). When analysed by year, the relationship was statistically
      significant in 2005 and 2006, but not statistically significant in each
      subsequent year. CONCLUSION: National prescribing trends suggest partial
      implementation of AHA guidelines for NSAID prescribing in CVD from 2005 to 2010.

PMID- 23163342
TI  - A conceptual framework for restoration of threatened plants: the effective model
      of American chestnut (Castanea dentata) reintroduction.
AB  - We propose a conceptual framework for restoration of threatened plant species
      that encourages integration of technological, ecological, and social spheres. A
      sphere encompasses ideas relevant to restoration and the people working within
      similar areas of influence or expertise. Increased capacity within a sphere and a
      higher degree of coalescing among spheres predict a greater probability of
      successful restoration. We illustrate this with Castanea dentata, a foundation
      forest tree in North America that was annihilated by an introduced pathogen; the
      species is a model that effectively merges biotechnology, reintroduction biology,
      and restoration ecology. Because of C. dentata's ecological and social
      importance, scientists have aggressively pursued blight resistance through
      various approaches. We summarize recent advancements in tree breeding and
      biotechnology that have emerged from C. dentata research, and describe their
      potential to bring new tools to bear on socio-ecological restoration problems.
      Successful reintroduction of C. dentata will also depend upon an enhanced
      understanding of its ecology within contemporary forests. We identify a critical
      need for a deeper understanding of societal influences that may affect setting
      and achieving realistic restoration goals. Castanea dentata may serve as an
      important model to inform reintroduction of threatened plant species in general
      and foundation forest trees in particular.

PMID- 23163345
TI  - NMR analysis of cross strand aromatic interactions in an 8 residue hairpin and a
      14 residue three stranded beta-sheet peptide.
AB  - Cross strand aromatic interactions between a facing pair of phenylalanine
      residues in antiparallel beta-sheet structures have been probed using two
      structurally defined model peptides. The octapeptide Boc-LFV(D)P(L)PLFV-OMe
      (peptide 1) favors the beta-hairpin conformation nucleated by the type II' beta
      turn formed by the (D)Pro-(L)Pro segment, placing Phe2 and Phe7 side chains in
      proximity. Two centrally positioned (D)Pro-(L)Pro segments facilitate the three
      stranded beta-sheet formation in the 14 residue peptide Boc
      LFV(D)P(L)PLFVA(D)P(L)PLFV-OMe (peptide 2) in which the Phe2/Phe7 orientations
      are similar to that in the octapeptide. The anticipated folded conformations of
      peptides 1 and 2 are established by the delineation of intramolecularly hydrogen
      bonded NH groups and by the observation of specific cross strand NOEs. The
      observation of ring current shifted aromatic protons is a diagnostic of close
      approach of the Phe2 and Phe7 side chains. Specific assignment of aromatic proton
      resonances using HSQC and HSQC-TOCSY methods allow an analysis of interproton
      NOEs between the spatially proximate aromatic rings. This approach facilitates
      specific assignments in systems containing multiple aromatic rings in spectra at
      natural abundance. Evidence is presented for a dynamic process which invokes a
      correlated conformational change about the C(alpha)-C(beta)(chi(1)) bond for the
      pair of interacting Phe residues. NMR results suggest that aromatic ring
      orientations observed in crystals are maintained in solution. Anomalous
      temperature dependence of ring current induced proton chemical shifts suggests
      that solvophobic effects may facilitate aromatic ring clustering in apolar
      solvents.

PMID- 23163343
TI  - Predictors of early and late target lesion revascularization after drug-eluting
      stent implantation.
AB  - INTRODUCTION: Recent studies have suggested the existence of a late catch-up
      phenomenon after drug-eluting stent (DES) implantation. The aim of this study is
      to identify predictors of early (<=1 year) and late (>1 year) target lesion
      revascularization (TLR) in DESs. METHODS: The COACT (CathOlic medical center
      percutAneous Coronary inTervention) registry was designed to evaluate the
      clinical outcomes after DES implantation. Data from 9,127 consecutive patients
      were reviewed, all of whom underwent percutaneous coronary intervention (PCI)
      with DES between January 2004 and December 2009, including 8,126 patients who
      received PCI with homogenous DES. RESULTS: During a median follow-up period of 24
      months (interquartile range, 11-41), the cumulative incidences of early and late
      TLR were 4.7% (95% confidence interval [CI], 4.2-5.1) and 3.3% (95% CI, 2.9-3.7).
      Independent predictors of early TLR were multivessel disease (odds ratio [OR]
      1.637; 95% CI 1.241-2.158, P < 0.001) and stent diameter (OR 0.614; 95% CI 0.437
      0.862, P = 0.005). Independent predictors of late TLR were stent diameter (OR
      0.567; 95% CI 0.367-0.875, P = 0.010), insulin-dependent diabetes mellitus (OR
      2.235; 95% CI 1.314-3.802, P = 0.003), first-generation DES (OR 5.104; 95% CI
      2.744-9.492, P < 0.001), and elevated levels of high-sensitivity C-reactive
      protein at follow-up coronary angiography >2 mg/dL (OR 1.616; 95% CI 1.173-2.226,
      P = 0.003). CONCLUSIONS: Although multivessel disease and stent diameter were
      associated with early TLR, late TLR was more associated with clinical
      comorbidities including insulin-dependent diabetes and procedural factors like
      the generation of the stent used and stent diameter. The risk factors for TLR may
      be markedly different at different time points during TLR.

PMID- 23163346
TI  - The evaluation of cisplatin effect on tubular function in children on
      chemotherapy.
AB  - The dose limiting side effect of cisplatin is nephrotoxicity. The aim of this
      study was to investigate tubular function in children who have received cisplatin
      and forced diuresis. We performed a cohort study on 20 children under 15 years of
      age with various type of malignancy on cisplatin-based chemotherapy. Twenty-four
      hour urine was collected in three periods: before the first, third, and fifth
      doses of cisplatin administration to check urine for sodium (Na), magnesium (Mg),
      uric acid, creatinine (Cr), phosphorus (P), calcium (Ca), beta-2 microglobulin,
      and N-acetyl-beta-D-glucosaminidase (NAG) levels. At the same time, blood samples
      were taken to check serum Cr, Na, Mg, Ca, P, and uric acid levels. Then, we
      compared the mean of glomerular filtration rate (GFR); fraction excretions (FE,%)
      of Na, Mg, and uric acid; tubular phosphorous reabsorption (TPR,%), 24-hour urine
      Ca (mg); urine beta-2 microglobulin (mcg/mL); and NAG (IU/L) in three periods of
      cisplatin administration. The FE of Na, Mg, and urine beta-2 microglobulin
      increased after administration of cisplatin but TPR, FE, uric acid, and NAG
      decreased in the 2nd and 3rd period compared to 1st period. GFR revealed a little
      change that was not significant. Urine calcium was decreased significantly in the
      second and third periods of cisplatin administration. Since the patients were
      hydrated for forced diuresis and received magnesium sulfate to prevent
      nephrotoxicity, we did not see significant tubular dysfunction. But we saw that
      urine calcium excretion decreased after cisplatin injection without any change in
      serum calcium in spite of preventive measures.

PMID- 23163347
TI  - Effect of estrogen on growth and apoptosis in esophageal adenocarcinoma cells.
AB  - The epidemiology of esophageal adenocarcinoma demonstrates a strong gender bias
      with a sex ratio of 8-9:1 in favor of males. A potential explanation for this is
      that estrogen might protect against esophageal adenocarcinoma. Estrogen has
      previously been shown to stimulate apoptosis in esophageal squamous cancer cells.
      However, the effect of estrogen on esophageal adenocarcinoma cells has not been
      determined. We used immunoblotting analysis to determine the expression of
      estrogen receptors, cell adhesion marker E-cadherin, and proliferation marker Ki
      67 in cell lines derived from esophageal adenocarcinoma (OE-19, OE-33) and
      Barrett's esophagus (QhTRT, ChTRT, GihTRT). Estrogen and selective estrogen
      receptor modulator (SERM)-dependent effects on cell growth were determined by the
      CellTiter-96 Aqueous Proliferation Assay. Apoptosis was determined by Annexin
      V/Propidium Iodide cell labeling and flow cytometry. We detected that
      physiological and supra-physiological concentrations of 17beta-estradiol and SERM
      decreased cell growth in esophageal adenocarcinoma cells. In Barrett's esophagus
      cells (QhTRT, ChTRT), decreased growth was also detected in response to
      estrogen/SERM. The level of estrogen receptor expression in the cell lines
      correlated with the level of anti-growth effects induced by the receptor
      agonists. Flow cytometry analysis confirmed estrogen/SERM stimulated apoptosis in
      esophageal adenocarcinoma cells. Estrogen/SERM treatments were associated with a
      decrease in the expression of Ki-67 and an increase in E-cadherin expression in
      esophageal adenocarcinoma cells. This study suggests that esophageal
      adenocarcinoma and Barrett's esophagus cells respond to treatment with selective
      estrogen receptor ligands, resulting in decreased cell growth and apoptosis.
      Further research to explore potential therapeutic applications is warranted. 

PMID- 23163349
TI  - Task specialization in two social spiders, Stegodyphus sarasinorum (Eresidae) and
      Anelosimus eximius (Theridiidae).
AB  - Understanding the social organization of group-living organisms is crucial for
      the comprehension of the underlying selective mechanisms involved in the
      evolution of cooperation. Division of labour and caste formation is restricted to
      eusocial organisms, but behavioural asymmetries and reproductive skew is common
      in other group-living animals. Permanently, social spiders form highly related
      groups with reproductive skew and communal brood care. We investigated task
      differentiation in nonreproductive tasks in two permanently and independently
      derived social spider species asking the following questions: Do individual
      spiders vary consistently in their propensity to engage in prey attack? Are
      individual spiders' propensities to engage in web maintenance behaviour
      influenced by their previous engagement in prey attack? Interestingly, we found
      that both species showed some degree of task specialization, but in distinctly
      different ways: Stegodyphus sarasinorum showed behavioural asymmetries at the
      individual level, that is, individual spiders that had attacked prey once were
      more likely to attack prey again, independent of their body size or hunger level.
      In contrast, Anelosimus eximius showed no individual specialization, but showed
      differentiation according to instar, where adult and subadult females were more
      likely to engage in prey attack than were juveniles. We found no evidence for
      division of labour between prey attack and web maintenance. Different solutions
      to achieve task differentiation in prey attack for the two species studied here
      suggest an adaptive value of task specialization in foraging for social spiders.

PMID- 23163348
TI  - Metallo-beta-lactamase structure and function.
AB  - beta-Lactam antibiotics are the most commonly used antibacterial agents and
      growing resistance to these drugs is a concern. Metallo-beta-lactamases are a
      diverse set of enzymes that catalyze the hydrolysis of a broad range of beta
      lactam drugs including carbapenems. This diversity is reflected in the
      observation that the enzyme mechanisms differ based on whether one or two zincs
      are bound in the active site that, in turn, is dependent on the subclass of beta
      lactamase. The dissemination of the genes encoding these enzymes among Gram
      negative bacteria has made them an important cause of resistance. In addition,
      there are currently no clinically available inhibitors to block metallo-beta
      lactamase action. This review summarizes the numerous studies that have yielded
      insights into the structure, function, and mechanism of action of these enzymes.

PMID- 23163350
TI  - High viability of cells encapsulated in degradable poly(carboxybetaine)
      hydrogels.
AB  - In this study, we report a degradable poly(carboxybetaine) (pCB) hydrogel,
      produced via a thiol-disulfide exchange reaction for cell encapsulation. A pCB
      dithiol was synthesized as a cross-linker and reacted with a pyridyl dithiol
      containing CB copolymer to form a hydrogel. We evaluated the biocompatibility of
      the pCB-based hydrogel via encapsulation of three cell types, including NIH3T3
      fibroblasts, MG63 osteoblast-like cells, and HepG2 hepatocarcinoma cells. Up to
      90% of cells retained their viability in the pCB hydrogel even at low cell
      seeding densities under serum-free conditions after a 9-day culture. Results are
      compared with a degradable poly(ethylene glycol) methacrylate (PEGMA) hydrogel,
      which showed very low cell viability under serum-free condition after a 3-day
      culture. We incorporated an RGD peptide into the CB hydrogel using a cysteine
      terminated cross-linker, which was shown to promote cell proliferation.

PMID- 23163352
TI  - Solid-state NMR structure determination of whole anchoring threads from the blue
      mussel Mytilus edulis.
AB  - The molecular structure of the blue mussel  Mytilus edulis  whole anchoring
      threads was studied by two-dimensional (13)C solid-state NMR on fully labeled
      fibers. This unique material proves to be well ordered at a molecular level
      despite its heterogeneous composition as evidenced by the narrow measured
      linewidths below 1.5 ppm. The spectra are dominated by residues in collagen
      environments, as determined from chemical shift analysis, and a complete two
      dimensional assignment (including minor amino acids) was possible. The best
      agreement between predicted and experimental backbone chemical shifts was
      obtained for collagen helices with torsion angles (-75 degrees , +150 degrees ).
      The abundant glycine and alanine residues can be resolved in up to five different
      structural environments. Alanine peaks could be assigned to collagen triple
      helices, beta-sheets (parallel and antiparallel), beta-turns, and unordered
      structures. The use of ATR-FTIR microscopy confirmed the presence of these
      structural environments and enabled their location in the core of the thread
      (collagen helices and antiparallel beta-sheets) or its cuticle (unordered
      structures). The approach should enable characterization at the molecular level
      of a wide range of byssus macroscopic properties.

PMID- 23163353
TI  - Optic disc neovascularization revealing neurosyphilis.
AB  - PURPOSE: To report a case of neurosyphilis revealed by bilateral optic disc
      neovascularization. DESIGN: Case report. METHODS: A 39-year-old man presented
      with a 6-month history of progressive visual loss (20/25 RE, 20/1200 LE) and
      transient headaches. Fundus examination demonstrated a 1+ vitritis, mild macular
      edema and large optic disc neovascularization in both eyes. Serological tests for
      syphilis were positive. RESULTS: Specific antibiotics and systemic steroids were
      undertaken and complete regression of disc neovascularization was observed within
      6 months. CONCLUSION: Optic disc neovascularization, which is a rare
      manifestation of chronic uveitis, may lead to the diagnosis of neurosyphilis and
      be successfully treated by specific antibiotic and steroid therapy.

PMID- 23163354
TI  - Confirmation of the configuration of 10-isothiocyanato-4-cadinene diastereomers
      through synthesis.
AB  - The marine sponge metabolite 10-isothiocyanato-4-cadinene (1) was first isolated
      by Garson et al. from Acanthella cavernosa in 2000. The same structure 1 was
      later reported by Wright et al. from the nudibranch Phyllidiella pustulosa and
      its sponge diet, but with different NMR data. The syntheses of both enantiomers
      of 1 were accomplished through the isothiocyanation of 10-isocyano-4-cadinene (2)
      previously synthesized by our group. The correct spectroscopic data and specific
      rotation value of the structure 1 were determined on the basis of the syntheses.
      The NMR data of synthetic 1 matched those of the isothiocyanate isolated by
      Garson and differed from those reported by Wright. The spectroscopic data and
      specific rotation values of 10-epi-10-isothiocyanato-4-cadinene (6) and di-1,6
      epi-10-isothiocyanato-4-cadinene (8) were also established through the syntheses
      of these diastereomers. Structure 6 has been reported as a natural product by
      Mitome et al., but the NMR data for the synthetic sample of 6 differ from those
      of the natural isolate.

PMID- 23163351
TI  - MicroRNA biogenesis: regulating the regulators.
AB  - MicroRNAs (miRNAs) function as 21-24 nucleotide guide RNAs that use partial base
      pairing to recognize target messenger RNAs and repress their expression. As a
      large fraction of protein-coding genes are under miRNA control, production of the
      appropriate level of specific miRNAs at the right time and in the right place is
      integral to most gene regulatory pathways. MiRNA biogenesis initiates with
      transcription, followed by multiple processing steps to produce the mature miRNA.
      Every step of miRNA production is subject to regulation and disruption of these
      control mechanisms has been linked to numerous human diseases, where the balance
      between the expression of miRNAs and their targets becomes distorted. Here we
      review the basic steps of miRNA biogenesis and describe the various factors that
      control miRNA transcription, processing, and stability in animal cells. The
      tremendous effort put into producing the appropriate type and level of specific
      miRNAs underscores the critical role of these small RNAs in gene regulation.

PMID- 23163357
TI  - Communication: vibrational study of a benzyl carbanion: deprotonated 2,4
      dinitrotoluene.
AB  - The bare deprotonated 2,4-dinitrotoluene [DNT-H](-) anion, formed by electrospray
      ionization and trapped in a Paul ion-trap, has been investigated by IR multiple
      photon dissociation (IRMPD) spectroscopy and quantum chemical calculations at the
      B3LYP/6-311++G** level. IRMPD spectra were recorded in the 950-1800 cm(-1)
      fingerprint range and interpreted by comparison with the calculated IR absorption
      spectra for different low-lying isomers. The sampled [DNT-H](-) species is found
      to involve deprotonation at the methyl group, yielding a benzyl carbanion 1',
      previously described as an amine complex in solution and here characterized by
      vibrational spectroscopy as an unperturbed gaseous species. Anion 1' is the most
      stable species among [DNT-H](-) isomers.

PMID- 23163356
TI  - Tactic responses to pollutants and their potential to increase biodegradation
      efficiency.
AB  - A significant number of bacterial strains are able to use toxic aromatic
      hydrocarbons as carbon and energy sources. In a number of cases, the evolution of
      the corresponding degradation pathway was accompanied by the evolution of tactic
      behaviours either towards or away from these toxic carbon sources. Reports are
      reviewed which show that a chemoattraction to heterogeneously distributed
      aromatic pollutants increases the bioavailability of these compounds and their
      biodegradation efficiency. An extreme form of chemoattraction towards aromatic
      pollutants, termed 'hyperchemotaxis', was described for Pseudomonas putida DOT
      T1E, which is based on the action of the plasmid-encoded McpT chemoreceptor.
      Cells with this phenotype were found of being able to approach and of
      establishing contact with undiluted crude oil samples. Although close McpT
      homologues are found on other degradation plasmids, the sequence of their ligand
      binding domains does not share significant similarity with that of NahY, the
      other characterized chemoreceptor for aromatic hydrocarbons. This may suggest the
      existence of at least two families of chemoreceptors for aromatic pollutants. The
      use of receptor chimers comprising the ligand-binding region of McpT for
      biosensing purposes is discussed.

PMID- 23163358
TI  - Path-integral Mayer-sampling calculations of the quantum Boltzmann contribution
      to virial coefficients of helium-4.
AB  - We present Mayer-sampling Monte Carlo calculations of the quantum Boltzmann
      contribution to the virial coefficients B(n), as defined by path integrals, for n
      = 2 to 4 and for temperatures from 2.6 K to 1000 K, using state-of-the-art ab
      initio potentials for interactions within pairs and triplets of helium-4 atoms.
      Effects of exchange are not included. The vapor-liquid critical temperature of
      the resulting fourth-order virial equation of state is 5.033(16) K, a value only
      3% less than the critical temperature of helium-4: 5.19 K. We describe an
      approach for parsing the Boltzmann contribution into components that reduce the
      number of Mayer-sampling Monte Carlo steps required for components with large per
      step time requirements. We estimate that in this manner the calculation of the
      Boltzmann contribution to B(3) at 2.6 K is completed at least 100 times faster
      than the previously reported approach.

PMID- 23163359
TI  - Stochastic operator-splitting method for reaction-diffusion systems.
AB  - Many biochemical processes at the sub-cellular level involve a small number of
      molecules. The local numbers of these molecules vary in space and time, and
      exhibit random fluctuations that can only be captured with stochastic
      simulations. We present a novel stochastic operator-splitting algorithm to model
      such reaction-diffusion phenomena. The reaction and diffusion steps employ
      stochastic simulation algorithms and Brownian dynamics, respectively. Through
      theoretical analysis, we have developed an algorithm to identify if the system is
      reaction-controlled, diffusion-controlled or is in an intermediate regime. The
      time-step size is chosen accordingly at each step of the simulation. We have used
      three examples to demonstrate the accuracy and robustness of the proposed
      algorithm. The first example deals with diffusion of two chemical species
      undergoing an irreversible bimolecular reaction. It is used to validate our
      algorithm by comparing its results with the solution obtained from a
      corresponding deterministic partial differential equation at low and high number
      of molecules. In this example, we also compare the results from our method to
      those obtained using a Gillespie multi-particle (GMP) method. The second example,
      which models simplified RNA synthesis, is used to study the performance of our
      algorithm in reaction- and diffusion-controlled regimes and to investigate the
      effects of local inhomogeneity. The third example models reaction-diffusion of
      CheY molecules through the cytoplasm of Escherichia coli during chemotaxis. It is
      used to compare the algorithm's performance against the GMP method. Our analysis
      demonstrates that the proposed algorithm enables accurate simulation of the
      kinetics of complex and spatially heterogeneous systems. It is also
      computationally more efficient than commonly used alternatives, such as the GMP
      method.

PMID- 23163360
TI  - Green's function for reversible geminate reaction with volume reactivity.
AB  - The kinetics of a diffusing particle near a reversible trap may be described by
      an extension of the Feynman-Kac equation to the case of reversible binding, which
      can occur within a finite reaction sphere. We obtain the Green's function
      solution for the Laplace transform of this equation when the particle is
      initially either bound or unbound. We study the solution in the time-domain by
      either inverting the Laplace transform numerically or propagating the partial
      differential equation in the time-domain. We show that integrals of this solution
      over the reaction sphere agree with previously obtained solutions.

PMID- 23163361
TI  - Electronic excitation in bulk and nanocrystalline alkali halides.
AB  - The lowest energy excitations in bulk alkali halides are investigated by
      considering five different excited state descriptions. It is concluded that
      excitation transfers one outermost halide electron in the fully ionic ground
      state to the lowest energy vacant s orbital of one closest cation neighbour to
      produce the excited state termed dipolar. The excitation energies of seven salts
      were computed using shell model description of the lattice polarization produced
      by the effective dipole moment of the excited state neutral halogen-neutral metal
      pair. Ab initio uncorrelated short-range inter-ionic interactions computed from
      anion wavefunctions adapted to the in-crystal environment were augmented by short
      range electron correlation contributions derived from uniform electron-gas
      density functional theory. Dispersive attractions including wavefunction overlap
      damping were introduced using reliable semi-empirical dispersion coefficients.
      The good agreement between the predicted excitation energies and experiment
      provides strong evidence that the excited state is dipolar. In alkali halide
      nanocrystals in which each ionic plane contains only four ions, the Madelung
      energies are significantly reduced compared with the bulk. This predicts that the
      corresponding intra-crystal excitation energies in the nanocrystals, where there
      are two excited states depending on whether the halide electron is transferred to
      a cation in the same or in the neighbouring plane, will be reduced by almost 2
      eV. For such an encapsulated KI crystal, it has been shown that the greater
      polarization in the excited state of the bulk crystal causes these reductions to
      be lowered to a 1.1 eV-1.5 eV range for the case of charge transfer to a
      neighbouring plane. For intra-plane charge transfer the magnitude of the
      polarization energy is further reduced thus causing the excitation in these
      encapsulated materials to be only 0.2 eV less than in the bulk crystal.

PMID- 23163362
TI  - Charge-leveling and proper treatment of long-range electrostatics in all-atom
      molecular dynamics at constant pH.
AB  - Recent development of constant pH molecular dynamics (CpHMD) methods has offered
      promise for adding pH-stat in molecular dynamics simulations. However, until now
      the working pH molecular dynamics (pHMD) implementations are dependent in part or
      whole on implicit-solvent models. Here we show that proper treatment of long
      range electrostatics and maintaining charge neutrality of the system are critical
      for extending the continuous pHMD framework to the all-atom representation. The
      former is achieved here by adding forces to titration coordinates due to long
      range electrostatics based on the generalized reaction field method, while the
      latter is made possible by a charge-leveling technique that couples proton
      titration with simultaneous ionization or neutralization of a co-ion in solution.
      We test the new method using the pH-replica-exchange CpHMD simulations of a
      series of aliphatic dicarboxylic acids with varying carbon chain length. The
      average absolute deviation from the experimental pK(a) values is merely 0.18
      units. The results show that accounting for the forces due to extended
      electrostatics removes the large random noise in propagating titration
      coordinates, while maintaining charge neutrality of the system improves the
      accuracy in the calculated electrostatic interaction between ionizable sites.
      Thus, we believe that the way is paved for realizing pH-controlled all-atom
      molecular dynamics in the near future.

PMID- 23163363
TI  - Comparisons of 2D IR measured spectral diffusion in rotating frames using pulse
      shaping and in the stationary frame using the standard method.
AB  - Multidimensional visible spectroscopy using pulse shaping to produce pulses with
      stable controllable phases and delays has emerged as an elegant tool to acquire
      electronic spectra faster and with greatly reduced instrumental and data
      processing errors. Recent migration of this approach using acousto-optic
      modulator (AOM) pulse shaping to the mid-infrared region has proved useful for
      acquiring two dimensional infrared (2D IR) vibrational echo spectra. The
      measurement of spectral diffusion in 2D IR experiments hinges on obtaining
      accurate 2D line shapes. To date, pulse shaping 2D IR has not been used to study
      the time-dependent spectral diffusion of a vibrational chromophore. Here we
      compare the spectral diffusion data obtained from a standard non-collinear 2D IR
      spectrometer using delay lines to the data obtained from an AOM pulse shaper
      based 2D IR spectrometer. The pulse shaping experiments are performed in
      stationary, partially rotating, and fully rotating reference frames and are the
      first in the infrared to produce 2D spectra collected in a fully rotating frame
      using a phase controlled pulse sequence. Rotating frame experiments provide a
      dramatic reduction in the number of time points that must be measured to obtain a
      2D IR spectrum, with the fully rotating frame giving the greatest reduction.
      Experiments were conducted on the transition metal carbonyl complex
      tricarbonylchloro(1,10-phenanthroline)rhenium(I) in chloroform. The time
      dependent data obtained from the different techniques and with different
      reference frames are shown to be in agreement.

PMID- 23163364
TI  - Quantification of transition dipole strengths using 1D and 2D spectroscopy for
      the identification of molecular structures via exciton delocalization:
      application to alpha-helices.
AB  - Vibrational and electronic transition dipole strengths are often good probes of
      molecular structures, especially in excitonically coupled systems of
      chromophores. One cannot determine transition dipole strengths using linear
      spectroscopy unless the concentration is known, which in many cases it is not. In
      this paper, we report a simple method for measuring transition dipole moments
      from linear absorption and 2D IR spectra that does not require knowledge of
      concentrations. Our method is tested on several model compounds and applied to
      the amide I(') band of a polypeptide in its random coil and alpha-helical
      conformation as modulated by the solution temperature. It is often difficult to
      confidently assign polypeptide and protein secondary structures to random coil or
      alpha-helix by linear spectroscopy alone, because they absorb in the same
      frequency range. We find that the transition dipole strength of the random coil
      state is 0.12 +/- 0.013 D(2), which is similar to a single peptide unit,
      indicating that the vibrational mode of random coil is localized on a single
      peptide unit. In an alpha-helix, the lower bound of transition dipole strength is
      0.26 +/- 0.03 D(2). When taking into account the angle of the amide I(')
      transition dipole vector with respect to the helix axis, our measurements
      indicate that the amide I(') vibrational mode is delocalized across a minimum of
      3.5 residues in an alpha-helix. Thus, one can confidently assign secondary
      structure based on exciton delocalization through its effect on the transition
      dipole strength. Our method will be especially useful for kinetically evolving
      systems, systems with overlapping molecular conformations, and other situations
      in which concentrations are difficult to determine.

PMID- 23163365
TI  - Insights into the ultraviolet spectrum of liquid water from model calculations:
      the different roles of donor and acceptor hydrogen bonds in water pentamers.
AB  - With a view toward a better understanding of changes in the peak position and
      shape of the first absorption band of water with condensation or temperature,
      results from electronic structure calculations using high level wavefunction
      based and time-dependent density functional methods are reported for water
      pentamers. Excitation energies, oscillator strengths, and redistributions of
      electron density are determined for the quasitetrahedral water pentamer in its
      C(2v) equilibrium geometry and for many pentamer configurations sampled from
      molecular simulation of liquid water. Excitations associated with surface
      molecules are removed in order to focus on those states associated with the
      central molecule, which are the most representative of the liquid environment.
      The effect of hydrogen bonding on the lowest excited state associated with the
      central molecule is studied by adding acceptor or donor hydrogen bonds to
      tetramer and trimer substructures of the C(2v) pentamer, and by sampling liquid
      like configurations having increasing number of acceptor or donor hydrogen bonds
      of the central molecule. Our results provide clear evidence that the blueshift of
      excitation energies upon condensation is essentially determined by acceptor
      hydrogen bonds, and the magnitudes of these shifts are determined by the number
      of such, whereas donor hydrogen bonds do not induce significant shifts in
      excitation energies. This qualitatively different role of donor and acceptor
      hydrogen bonds is understood in terms of the different roles of the 1b(1) monomer
      molecular orbitals, which establishes an intimate connection between the valence
      hole and excitation energy shifts. Since the valence hole of the lowest
      excitation associated with the central molecule is found to be well localized in
      all liquid-like hydrogen bonding environments, with an average radius of gyration
      of ~1.6 A that is much lower than the nearest neighbor O-O distance, a clear and
      unambiguous connection between hydrogen bonding environments and excitation
      energy shifts can be established. Based on these results, it is concluded that
      peak position of the first absorption band is mainly determined by the relative
      distribution of single and double acceptor hydrogen bonding environments, whereas
      the shape of the first absorption band is mainly determined by the relative
      distribution of acceptor and broken acceptor hydrogen bonding environments. The
      temperature dependence of the peak position and shape of the first absorption
      band can be readily understood in terms of changes to these relative populations.

PMID- 23163366
TI  - Infrared spectroscopy of HOOO and DOOO in 4He nanodroplets.
AB  - The HOOO hydridotrioxygen radical and its deuterated analog (DOOO) have been
      isolated in helium nanodroplets following the in situ association reaction
      between OH and O(2). The infrared spectrum in the 3500-3700 cm(-1) region reveals
      bands that are assigned to the nu(1) (OH stretch) fundamental and nu(1) + nu(6)
      (OH stretch plus torsion) combination band of the trans-HOOO isomer. The helium
      droplet spectrum is assigned on the basis of a detailed comparison to the
      infrared spectrum of HOOO produced in the gas phase [E. L. Derro, T. D. Sechler,
      C. Murray, and M. I. Lester, J. Chem. Phys. 128, 244313 (2008)]. Despite the
      characteristic low temperature and rapid cooling of helium nanodroplets, there is
      no evidence for the formation of a weakly bound OH-O(2) van der Waals complex,
      which implies the absence of a kinetically significant barrier in the entrance
      channel of the reaction. There is also no spectroscopic evidence for the
      formation of cis-HOOO, which is predicted by theory to be nearly isoenergetic to
      the trans isomer. Under conditions that favor the introduction of multiple O(2)
      molecules to the droplets, bands associated with larger H/DOOO-(O(2))(n) clusters
      are observed shifted ~1-10 cm(-1) to the red of the trans-H/DOOO nu(1) bands.

PMID- 23163367
TI  - Inelastic collisions of the uracil molecules with electrons.
AB  - Ionization and excitation of the uracil molecules by electron impact is
      investigated. Production of positive ions of uracil molecules (nucleic acid base)
      was studied using a crossed electron and molecular beam technique. The method
      developed by the authors enabled the molecular beam intensity to be measured and
      the electron dependences and the absolute values of the total cross sections of
      production of both positive ions to be determined. It is shown that the total
      positive uracil ion production cross section reaches its maximal value of (1.0 +/
      0.1) * 10(-15) cm(2) at the 95 eV electron energy. Dissociative ionization cross
      sections were also determined. The luminescence spectra of isolated uracil
      molecules in the wavelength range of 200-500 nm under the influence of slow
      electrons are obtained. In the spectrum, more than 20 spectral bands and lines at
      100 eV electron energy are observed. It is shown that the uracil radiation
      spectrum is formed by the processes of molecules dissociative excitation,
      dissociative excitation with ionization, excitation of electronic levels of the
      initial molecule and molecular ion.

PMID- 23163368
TI  - Time-resolved photoelectron imaging of excited state relaxation dynamics in
      phenol, catechol, resorcinol, and hydroquinone.
AB  - Time-resolved photoelectron imaging was used to investigate the dynamical
      evolution of the initially prepared S(1) (pipi*) excited state of phenol
      (hydroxybenzene), catechol (1,2-dihydroxybenzene), resorcinol (1,3
      dihydroxybenzene), and hydroquinone (1,4-dihydroxybenzene) following excitation
      at 267 nm. Our analysis was supported by ab initio calculations at the coupled
      cluster and CASSCF levels of theory. In all cases, we observe rapid (<1 ps)
      intramolecular vibrational redistribution on the S(1) potential surface. In
      catechol, the overall S(1) state lifetime was observed to be 12.1 ps, which is 1
      2 orders of magnitude shorter than in the other three molecules studied. This may
      be attributed to differences in the H atom tunnelling rate under the barrier
      formed by a conical intersection between the S(1) state and the close lying S(2)
      (pisigma*) state, which is dissociative along the O-H stretching coordinate.
      Further evidence of this S(1)/S(2) interaction is also seen in the time-dependent
      anisotropy of the photoelectron angular distributions we have observed. Our data
      analysis was assisted by a matrix inversion method for processing photoelectron
      images that is significantly faster than most other previously reported
      approaches and is extremely quick and easy to implement.

PMID- 23163370
TI  - Evaluation of the nonlinear optical properties for an expanded porphyrin Huckel
      Mobius aromaticity switch.
AB  - The conformational flexibility of the expanded porphyrins allows them to achieve
      different topologies with distinct aromaticities and nonlinear optical properties
      (NLOP). For instance, it is possible to switch between Mobius and Huckel
      topologies applying only small changes in the external conditions or in the
      structure of the ring. In this work, we evaluate the electronic and vibrational
      contributions to static and dynamic NLOP of the Huckel and Mobius conformers of
      A,D-di-p-benzi[28]hexaphyrin(1.1.1.1.1.1) synthesized by Latos-Grazynski and co
      workers [Angew. Chem., Int. Ed. 46, 7869 (2007)]. Calculations are performed at
      the HF, M052X, and CAM-B3LYP levels using the 6-31G, 6-311G(d), and 6-31+G(d)
      basis sets. Our results conclude that M052X/6-31G and CAM-B3LYP/6-31G methods
      provide a correct qualitative description of the electronic and vibrational
      contributions for the NLOP of expanded porphyrins. The studied systems show high
      NLOP with large differences between the Mobius and Huckel conformations (around 1
      * 10(6) a.u. for gamma). The obtained results indicate that the expanded
      porphyrins are promising systems to manufacture Huckel-to-Mobius topological
      switches.

PMID- 23163369
TI  - Experimental and theoretical investigations on photoabsorption and
      photoionization of trimethylphosphate in the vacuum-ultraviolet energy range.
AB  - In this work, we report a joint experimental-theoretical investigation on
      interaction of vacuum-ultraviolet radiation with trimethylphosphate (TMP)
      molecule (C(3)H(9)O(4)P) in gas phase. This species together with tetrahydrofuran
      (THF) are model compounds of deoxyribose nucleic acids (DNA)/ribose nucleic acids
      (RNA) backbone. Absolute photoabsorption cross sections (sigma(a)) and ionization
      yields (eta) are measured using the double-ion-chamber technique in the 11.0
      21.45 eV energy range. Photoionization (sigma(i)) and neutral-decay (sigma(n))
      cross sections in absolute scale are also derived. Moreover, theoretical
      photoabsorption cross sections are calculated using the time-dependent density
      functional theory from the excitation threshold up to 16 eV. Good agreement
      between the present calculated and experimental photoabsorption cross sections in
      the 11.0-14.5 eV range is encouraging. Also, the present measured data of
      sigma(a) and sigma(i) for TMP are about 1.3 and 1.5 times of those of THF,
      respectively. Thus, the experimental evidences that the majority of strand breaks
      being located at sugar rings in the irradiated DNA/RNA backbone moiety may be
      induced by a possible migration of the hole, initially created at phosphate
      group, to the linked sugar groups. Finally, absolute partial photoionization
      cross sections are derived from the experimental time-of-flight mass spectra.

PMID- 23163371
TI  - On pi-stacking, C-H/pi, and halogen bonding interactions in halobenzene clusters:
      resonant two-photon ionization studies of chlorobenzene.
AB  - Noncovalent interactions such as hydrogen bonding, pi-pi stacking, CH/pi
      interactions, and halogen bonding play crucial roles in a broad spectrum of
      chemical and biochemical processes, and can exist in cooperation or competition.
      Here we report studies of the homoclusters of chlorobenzene, a prototypical
      system where pi-pi stacking, CH/pi interactions, and halogen bonding interactions
      may all be present. The electronic spectra of chlorobenzene monomer and clusters
      (Clbz)(n) with n = 1-4 were obtained using resonant 2-photon ionization in the
      origin region of the S(0)-S(1) (pipi*) state of the monomer. The cluster spectra
      show in all cases a broad spectrum whose center is redshifted from the monomer
      absorption. Electronic structure calculations aid in showing that the spectral
      broadening arises in large part from inhomogeneous sources, including the
      presence of multiple isomers and Franck-Condon (FC) activity associated with
      geometrical changes induced by electronic excitation. Calculations at the M06
      2x/aug-cc-pVDZ level find in total five minimum energy structures for the dimer,
      four pi-stacked structures, and one T-shaped, and six representative minimum
      energy structures were found for the trimer. The calculated time-dependent
      density functional theory spectra using range-separated and meta-GGA hybrid
      functionals show that these isomers absorb over a range that is roughly
      consistent with the breadth of the experimental spectra, and the calculated
      absorptions are redshifted with respect to the monomer transition, in agreement
      with experiment. Due to the significant geometry change in the electronic
      transition, where for the dimer a transition from a parallel displaced to
      sandwich structure occurs with a reduced separation of the two monomers,
      significant FC activity is predicted in low frequency intermolecular modes.

PMID- 23163373
TI  - Size-dependent chemical reactivity of porous graphene for purification of exhaust
      gases.
AB  - From the structural characteristics of pores evolving from the vacancy, the
      structure-dependent nature of localized states, and the role of electronic states
      in the reaction, we elucidate size effects on the chemical reactivity of porous
      graphene using density functional theory. The coupling of conjugated pi electrons
      of graphene with localized defect states allows for the reduction reaction or
      adsorption of exhaust gases on the edge atoms. The charge redistribution,
      ascertained from the coupling response, activates the weak C-C bond states at the
      corners, facilitating the dissociation of exhaust gas (e.g., NO). The size
      matching effect makes that the dissociation barrier of NO on the vacancy is
      smaller than 8.30 kcal/mol; whereas, larger pores only capture NO. Following the
      coupling-response mechanism, we propose the structural requirements for chemical
      applications of porous graphene: the shape and size of the pores are comparable
      in scale with those of purified molecules.

PMID- 23163372
TI  - Dissociation mechanisms of excited CH3X (X = Cl, Br, and I) formed via high
      energy electron transfer using alkali metal targets.
AB  - High-energy electron transfer dissociation (HE-ETD) on collisions with alkali
      metal targets (Cs, K, and Na) was investigated for CH(3)X(+) (X = Cl, Br, and I)
      ions by a charge inversion mass spectrometry. Relative peak intensities of the
      negative ions formed via HE-ETD strongly depend on the precursor ions and the
      target alkali metals. The dependency is explained by the exothermicities of the
      respective dissociation processes. Peak shapes of the negative ions, especially
      of the X(-) ions, which comprise a triangle and a trapezoid, also strongly depend
      on the precursor ions and the target alkali metals. The trapezoidal part of the
      I(-) peak observed with the Na target is more dominant and much broader than that
      with the Cs target. This dependence on the targets shows an inverse relation
      between the peak width and the available energy, which corresponds to the
      exothermicity assuming formation of fragment pair in their ground internal
      states. From a comparison of the kinetic energy release value calculated from the
      trapezoidal shape of I(-) with the available energy of the near-resonant level on
      the CH(3)I potential energy curve reported by ab initio calculations, the
      trapezoidal part is attributed to the dissociation to CH(3) + I((2)P(3/2)) via
      the repulsive (3)Q(1) state of CH(3)I, which is not dominant in the photo
      dissociation of CH(3)I. The observation of trapezoid shape of the CH(2)I(-) peak
      with the Cs target indicates spontaneous dissociation via repulsive potential
      from the (3)R(2) Rydberg state, although the correlation between the (3)R(2)
      Rydberg state and relevant repulsive states has not been reported by any
      theoretical calculation.

PMID- 23163374
TI  - Fluorescence emission of Ca-atom from photodissociated Ca2 in Ar-doped helium
      droplets. I. Experimental.
AB  - The Ca(2) -> Ca(4s4p(1)P) + Ca(4s(2)(1)S) photodissociation was investigated in a
      He droplet isolation experiment where the droplets are doped by Ar atoms.
      Fluorescence spectra associated with the Ca(4s4p(1)P -> 4s(2)(1)S) emission were
      recorded as a function of the average number of Ar atoms per droplet. Three
      contributions were observed depending on whether the emitting Ca atoms are free,
      bound to helium atoms or bound to argon atoms. Moreover, the full Ca(4s4p(1)P ->
      4s(2)(1)S) fluorescence emission was recorded as a function of the wavelength of
      the photodissociation laser, hence providing the action spectrum of the Ca(2) ->
      Ca(4s4p(1)P) + Ca(4s(2)(1)S) process. The latter spectrum suggests that in He
      droplets doped by argon, Ca atoms are attracted inside the droplet where they
      associate as Ca(2). Full analysis of the spectra indicate that the emission of Ca
      bound to a single Ar atom is redshifted by 94 cm(-1) with respect to the emission
      of free Ca.

PMID- 23163375
TI  - Fluorescence emission of Ca-atom from photodissociated Ca2 in Ar doped helium
      droplets. II. Theoretical.
AB  - The stability of the ground or excited state calcium atom in an argon-doped
      helium droplet has been investigated using an extension of the helium density
      functional method to treat clusters. This work was motivated by the experimental
      study presented in a companion paper, hereafter called Paper I [A. Masson, M.
      Briant, J. M. Mestdagh, M. A. Gaveau, A. Hernando, and N. Halberstadt, J. Chem.
      Phys. 137, 184310 (2012)], which investigated Ca(2) photodissociation in an argon
      doped helium droplet and the nature of the fluorescent species. It is found that
      one single argon atom is sufficient to bring the calcium atom inside the droplet,
      for droplets of over 200 helium atoms. The absorption and emission spectra of
      CaAr(M) (M = 0-7) clusters have been simulated using the recently developed
      density sampling method to describe the influence of the helium environment.
      Absorption spectra exhibit broad, double bands that are significantly blueshifted
      with respect to the calcium atomic line. The emission spectra are less broad and
      redshifted with respect to the calcium resonance line. The shifts are found to be
      additive only for M <= 2, because only the first two argon atoms are located in
      equivalent positions around the calcium p orbital. This finding gives a
      justification for the fit presented in the companion paper, which uses the
      observed shifts in the emission spectra as a function of argon pressure to deduce
      the shifts as a function of the number of argon atoms present in the cluster. An
      analysis of this fit is presented here, based on the calculated shifts. It is
      concluded that the emitting species following Ca(2) photodissociation in an argon
      doped droplet in Paper I could be Ca*Ar(M) in a partly evaporated droplet where
      less than 200 helium atoms remain.

PMID- 23163376
TI  - Vibrational quenching of excitonic splittings in H-bonded molecular dimers:
      adiabatic description and effective mode approximation.
AB  - The quenching of the excitonic splitting in hydrogen-bonded molecular dimers has
      been explained recently in terms of exciton coupling theory, involving Forster's
      degenerate perturbation theoretical approach [P. Ottiger, S. Leutwyler, and H.
      Koppel, J. Chem. Phys. 136, 174308 (2012)]. Here we provide an alternative
      explanation based on the properties of the adiabatic potential energy surfaces.
      In the proper limit, the lower of these surfaces exhibits a double-minimum shape,
      with an asymmetric distortion that destroys the geometric equivalence of the
      excitonically coupled monomers. An effective mode is introduced that exactly
      reproduces the energy gain and amount of distortion that occurs in a multi
      dimensional normal coordinate space. This allows to describe the quenched exciton
      splitting as the energy difference of the two (S(1) and S(2)) vibronic band
      origins in a one-dimensional (rather than multi-dimensional) vibronic
      calculation. The agreement with the earlier result (based on Forster theory) is
      excellent for all five relevant cases studied. A simple rationale for the
      quenched exciton splitting as nonadiabatic tunneling splitting on the lower
      double-minimum potential energy surface is given.

PMID- 23163377
TI  - A multilayered-representation quantum mechanical/molecular mechanics study of the
      S(N)2 reaction of CH3Br + OH(-) in aqueous solution.
AB  - The bimolecular nucleophilic substitution (S(N)2) reaction of CH(3)Br and OH(-)
      in aqueous solution was investigated using a multilayered-representation quantum
      mechanical and molecular mechanics methodology. Reactant complex, transition
      state, and product complex are identified and characterized in aqueous solution.
      The potentials of mean force are computed under both the density function theory
      and coupled-cluster single double (triple) (CCSD(T)) levels of theory for the
      reaction region. The results show that the aqueous environment has a significant
      impact on the reaction process. The solvation effect and the polarization effect
      combined raise the activation barrier height by ~16.2 kcal/mol and the solvation
      effect is the dominant contribution to the potential of mean force. The
      CCSD(T)/MM representation presents a free energy activation barrier height of
      22.8 kcal/mol and the rate constant at 298 K of 3.7 * 10(-25) cm(3) molecule(-1)
      s(-1) which agree very well with the experiment values at 23.0 kcal/mol and 2.6 *
      10(-25) cm(3) molecule(-1) s(-1), respectively.

PMID- 23163378
TI  - Hybrid functional study rationalizes the simple cubic phase of calcium at high
      pressures.
AB  - Simple cubic (SC) phase has been long experimentally determined as the high
      pressure phase III of elemental calcium (Ca) since 1984. However, recent density
      functional calculations within semi-local approximation showed that this SC phase
      is structurally unstable by exhibiting severely imaginary phonons, and is
      energetically unstable with respect to a theoretical body-centered tetragonal
      I4(1)/amd structure over the pressure range of phase III. These calculations
      generated extensive debates on the validity of SC phase. Here we have re-examined
      the SC structure by performing more precise density functional calculations
      within hybrid functionals of Heyd-Scuseria-Erhzerhof and PBE0. Our calculations
      were able to rationalize fundamentally the phase stability of SC structure over
      all other known phases by evidence of its actual energetic stability above 33 GPa
      and its intrinsically dynamical stability without showing any imaginary phonons
      in the entire pressure range studied. We further established that the long
      thought theoretical I4(1)/amd structure remains stable in a narrow pressure range
      before entering SC phase and is actually the structure of experimental Ca-III(')
      synthesized recently at low temperature 14 K as supported by the excellent
      agreement between our simulated x-ray diffraction patterns and the experimental
      data. Our results shed strong light on the crucial role played by the precise
      electron exchange energy in a proper description of the potential energy of Ca.

PMID- 23163379
TI  - A molecular dynamics study of the equation of state and the structure of
      supercooled aqueous solutions of methanol.
AB  - We perform molecular dynamics computer simulations in order to study the equation
      of state and the structure of supercooled aqueous solutions of methanol at
      methanol mole fractions x(m) = 0.05 and x(m) = 0.10. We model the solvent using
      the TIP4P/2005 potential and the methanol using the OPLS-AA force field. We find
      that for x(m) = 0.05 the behavior of the equation of state, studied in the P - T
      and P - rho planes, is consistent with the presence of a liquid-liquid phase
      transition, reminiscent of that previously found for x(m) = 0. We estimate the
      position of the liquid-liquid critical point to be at T = 193 K, P = 96 MPa, and
      rho = 1.003 g/cm(3). When the methanol mole fraction is doubled to x(m) = 0.10 no
      liquid-liquid transition is observed, indicating its possible disappearance at
      this concentration. We also study the water-water and water-methanol structure in
      the two solutions. We find that down to low temperature methanol can be
      incorporated into the water structure for both x(m) = 0.05 and x(m) = 0.10.

PMID- 23163380
TI  - A comparison of the solvation thermodynamics of amino acid analogues in water, 1
      octanol and 1-n-alkyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide ionic
      liquids by molecular simulation.
AB  - A computational approach is developed to quantitatively study the solvation
      thermodynamics of amino acid analogues in ionic liquids via molecular simulation.
      The solvation thermodynamics of amino acid analogues in ionic liquids is
      important for an understanding of protein-ionic liquid interactions, shedding
      insight into the structure and solubility of proteins, and the activity of
      enzymes in ionic liquids. This information is additionally key to developing
      novel extraction processes. As a result of the challenge of quantitatively
      describing the solvation behavior of ionic liquids, a key outcome of the present
      study is the development of a "hydrophobicity" scale to quantitatively describe
      the amino acid analogues. The scale allows one to separate the results of both
      the hydrophobic and hydrophillic analogues, simplifying an understanding of the
      observed trends. Equipped with the proposed hydrophobicity scale, one needs only
      perform conventional solvation free energy calculations of the amino acid
      analogues in the ionic liquids of interest. The necessary simulation tools are
      available in most open-source simulation software, facilitating the adoption of
      this approach by the simulation community at large. We have studied the case of
      varying the cation alkyl-chain length of a 1-n-alkyl-3-methylimidazolium cation
      paired with the bis(trifluoromethylsulfonyl)imide anion. The findings suggest
      that a judicious selection of both the cation and anion could potentially lead to
      a solvent for which the amino acid analogues have an affinity far greater than
      that for both water and a non-polar reference solvent.

PMID- 23163381
TI  - Structure and interactions in fluids of prolate colloidal ellipsoids: comparison
      between experiment, theory, and simulation.
AB  - The microscopic structure of fluids of simple spheres is well known. However, the
      constituents of most real-life fluids are non-spherical, leading to a coupling
      between the rotational and translational degrees of freedom. The structure of
      simple dense fluids of spheroids - ellipsoids of revolution - was only recently
      determined by direct experimental techniques [A. P. Cohen, E. Janai, E. Mogilko,
      A. B. Schofield, and E. Sloutskin, Phys. Rev. Lett. 107, 238301 (2011)]. Using
      confocal microscopy, it was demonstrated that the structure of these simple
      fluids cannot be described by hard particle models based on the widely used
      Percus-Yevick approximation. In this paper, we describe a new protocol for
      determining the shape of the experimental spheroids, which allows us to expand
      our previous microscopy measurements of these fluids. To avoid the approximations
      in the theoretical approach, we have also used molecular dynamics simulations to
      reproduce the experimental radial distribution functions g(r) and estimate the
      contribution of charge effects to the interactions. Accounting for these charge
      effects within the Percus-Yevick framework leads to similar agreement with the
      experiment.

PMID- 23163382
TI  - Polymorphic phases of sp3-hybridized superhard CN.
AB  - It is well established that carbon nitride (CN) is a potential superhard material
      as its bond in network structures is slightly shorter than the C-C bond in
      diamond. However, the structure of superhard CN materials is yet to be determined
      experimentally. We have performed an extensive structural search for the high
      pressure crystalline phases of CN using the particle swarm optimization
      technique; seven low-energy polymorphic structures of sp(3)-hybridized CN have
      been found in an unbiased search. Density-functional theory calculations indicate
      that, among the seven low-energy crystalline structures, Pnnm structure (8
      atoms/cell) is energetically more favorable than the previously reported most
      stable crystalline structure with 1:1 stoichiometry. Furthermore, Pnnm possesses
      the highest hardness (62.3 GPa). Formation enthalpies demonstrate that this
      material can be synthesized at pressure 10.9 GPa, lower than needed by beta
      C(3)N(4) (14.1 GPa).

PMID- 23163383
TI  - Chemical precipitation structures formed by drops impacting on a deep pool.
AB  - The experiments described here are at the intersection of two dynamical systems
      with long pedigrees for forming interesting patterns: liquid droplet impacts and
      precipitation membranes. Drops of calcium chloride solution have been allowed to
      impact on a deep pool of sodium silicate solution. The precipitation structures
      produced by this method, and how these structures subsequently evolve, have been
      observed. Many interesting patterns can be formed from this process. It is
      observed that the precipitation patterns produced are sensitive to the shape of
      the drop when it impacts the pool's surface. Also, at large drop heights, we
      determine two critical Weber numbers: one for forming a skirt around the
      structures and the other for breakup of the structures. On longer time scales,
      open tubes grow from the closed precipitation shell produced at lower drop
      heights. These tubes can appear in large numbers with nearly identical sizes and
      diameters as small as 50 MUm.

PMID- 23163384
TI  - Understanding adsorption-induced structural transitions in metal-organic
      frameworks: from the unit cell to the crystal.
AB  - Breathing transitions represent recently discovered adsorption-induced structural
      transformations between large-pore and narrow-pore conformations in bi-stable
      metal-organic frameworks such as MIL-53. We present a multiscale physical
      mechanism of the dynamics of breathing transitions. We show that due to interplay
      between host framework elasticity and guest molecule adsorption, these
      transformations on the crystal level occur via layer-by-layer shear. We construct
      a simple Hamiltonian that describes the physics of host-host and host-guest
      interactions on the level of unit cells and reduces to one effective dimension
      due to the long-range elastic cell-cell interactions. We then use this
      Hamiltonian in Monte Carlo simulations of adsorption-desorption cycles to study
      how the behavior of unit cells is linked to the transition mechanism at the
      crystal level through three key physical parameters: the transition energy
      barrier, the cell-cell elastic coupling, and the system size.

PMID- 23163385
TI  - Simulations of structural and dynamic anisotropy in nano-confined water between
      parallel graphite plates.
AB  - We use molecular dynamics simulations to study the structure, dynamics, and
      transport properties of nano-confined water between parallel graphite plates with
      separation distances (H) from 7 to 20 A at different water densities with an
      emphasis on anisotropies generated by confinement. The behavior of the confined
      water phase is compared to non-confined bulk water under similar pressure and
      temperature conditions. Our simulations show anisotropic structure and dynamics
      of the confined water phase in directions parallel and perpendicular to the
      graphite plate. The magnitude of these anisotropies depends on the slit width H.
      Confined water shows "solid-like" structure and slow dynamics for the water
      layers near the plates. The mean square displacements (MSDs) and velocity
      autocorrelation functions (VACFs) for directions parallel and perpendicular to
      the graphite plates are calculated. By increasing the confinement distance from H
      = 7 A to H = 20 A, the MSD increases and the behavior of the VACF indicates that
      the confined water changes from solid-like to liquid-like dynamics. If the
      initial density of the water phase is set up using geometric criteria (i.e.,
      distance between the graphite plates), large pressures (in the order of ~10
      katm), and large pressure anisotropies are established within the water. By
      decreasing the density of the water between the confined plates to about 0.9 g
      cm(-3), bubble formation and restructuring of the water layers are observed.

PMID- 23163386
TI  - Nano-environment effects on the luminescence properties of Eu(3+)-doped
      nanocrystalline SnO2 thin films.
AB  - Nanocrystalline tin (IV) oxide thin films doped with Eu(3+) ions are synthesized
      using a simple spin-coating method followed by postannealing in an O(2) flow at
      700  degrees C. Transmission electron microscopy and x-ray photoelectron
      spectroscopy studies illustrate the incorporation of Eu(3+) ions in the films
      with a high atomic percentage of 2.7%-7.7%, which is found to be linearly
      dependent on the initial concentration of Eu(3+) in the precursor solution.
      Glancing incidence x-ray diffraction results show that the crystalline grain
      sizes decrease with increasing the Eu(3+) concentration and decreasing the
      postannealing temperature with the emergence of the Eu(2)Sn(2)O(7) phase at high
      Eu(3+) concentrations (>=5.3 at.%). Luminescence spectra of these doped samples
      show the characteristic narrow-band magnetic dipole emission at 593 nm and
      electric dipole emission at 614 nm of the Eu(3+) ions, arising from UV absorption
      at the SnO(2) band-edge followed by energy transfer to the emission centers.
      Manipulating the crystallite size, composition, and defect density of the samples
      greatly affects the absorption edge, energy transfer, and therefore the emission
      spectra. These modifications in the environment of the Eu(3+) ions allow the
      emission to be tuned from pure orange characteristic Eu(3+) emission to the
      broadband emission corresponding to the combination of strong characteristic
      Eu(3+) emission with the intense defect emissions.

PMID- 23163387
TI  - Enhancement of Ag cluster mobility on Ag surfaces by chloridation.
AB  - To understand the role of chlorine in the stability and the observed
      fragmentation of Ag dendritic nanostructures, we have studied computationally two
      model systems using density functional theory. The first one relates to diffusion
      of Ag(n) and Ag(n)Cl(m) (n = 1-4) clusters on an Ag(111) surface, and the second
      demonstrates interaction strength of (Ag(55))(2) dimers with and without
      chloridation. Based on our calculated energy barriers, Ag(n)Cl(m) clusters are
      more mobile than Ag(n) clusters for n = 1-4. The binding energy between two
      Ag(55) clusters is significantly reduced by surface chloridation. Bond weakening
      and enhanced mobility are two important mechanisms underlying corrosion and
      fragmentation processes.

PMID- 23163388
TI  - Modified PRISM theory for confined polymers.
AB  - We propose a modified polymer reference interaction site model (PRISM) to
      describe the interfacial density profiles of polymers in contact with planar and
      curved solid surfaces. In the theoretical approach, a bridge function derived
      from density functional method is included. In description of hard-sphere polymer
      at planar and curved surfaces with an arbitrary external field, the effect of
      modification has been validated by the available simulation data, except for low
      density system. When extended to confined real systems, the modified theoretical
      model also shows an encouraging prospect in description of the interfacial
      structure and properties.

PMID- 23163389
TI  - Transport properties of suspensions-critical assessment of Beenakker-Mazur
      method.
AB  - The Beenakker-Mazur method of calculation of transport coefficients for
      suspensions has been analyzed. The analysis relies on calculation of the
      hydrodynamic function and the effective viscosity with higher accuracy and
      comparison of these characteristics to the original Beennakker-Mazur results.
      Comparison to numerical simulations is also given. Our calculations go along with
      the idea of Beenakker and Mazur, but avoid unnecessary approximations. Our higher
      accuracy results differ significantly from results obtained initially by
      Beenakker and Mazur for volume fractions phi > 25%. Moreover, our results agree
      with the precise numerical simulations of Abade and Ladd for volume fractions phi
      < 15% and volume fractions phi ~ 45%, whereas for volume fractions 15% < phi <
      40%, we observe pronounced discrepancies.

PMID- 23163390
TI  - Spinodal assisted growing dynamics of critical nucleus in polymer blends.
AB  - In metastable polymer blends, nonclassical critical nucleus is not a drop of
      stable phase in core wrapped with a sharp interface, but a diffuse structure
      depending on the metastability. Thus, forming a critical nucleus does not mean
      the birth of a new phase. In the present work, the nonclassical growing dynamics
      of the critical nucleus is addressed in the metastable polymer blends by
      incorporating self-consistent field theory and external potential dynamics
      theory, which leads to an intuitionistic description for the scattering
      experiments. The results suggest that the growth of nonclassical critical nucleus
      is controlled by the spinodal-decomposition which happens in the region
      surrounding the nucleus. This leads to forming the shell structures around the
      nucleus.

PMID- 23163391
TI  - Cluster glasses of ultrasoft particles.
AB  - We present molecular dynamics (MD) simulations results for dense fluids of
      ultrasoft, fully penetrable particles. These are a binary mixture and a
      polydisperse system of particles interacting via the generalized exponential
      model, which is known to yield cluster crystal phases for the corresponding
      monodisperse systems. Because of the dispersity in the particle size, the systems
      investigated in this work do not crystallize and form disordered cluster phases.
      The clustering transition appears as a smooth crossover to a regime in which
      particles are mostly located in clusters, isolated particles being infrequent.
      The analysis of the internal cluster structure reveals microsegregation of the
      big and small particles, with a strong homo-coordination in the binary mixture.
      Upon further lowering the temperature below the clustering transition, the motion
      of the clusters' centers-of-mass slows down dramatically, giving way to a cluster
      glass transition. In the cluster glass, the diffusivities remain finite and
      display an activated temperature dependence, indicating that relaxation in the
      cluster glass occurs via particle hopping in a nearly arrested matrix of
      clusters. Finally we discuss the influence of the microscopic dynamics on the
      transport properties by comparing the MD results with Monte Carlo simulations.

PMID- 23163392
TI  - Compression studies of face-to-face pi-stacking interaction in sodium squarate
      salts: Na2C4O4 and Na2C4O4?3H2O.
AB  - High-pressure Raman scattering and synchrotron X-ray diffraction measurements of
      sodium squarate (Na(2)C(4)O(4), SS) are performed in a diamond anvil cell. SS
      possesses a rare, but typical structure, which can show the effect of face-to
      face pi-stacking without interference of other interactions. At ~11 GPa, it
      undergoes a phase transition, identified as a symmetry transformation from
      P2(1)/c to P2(1). From high-pressure Raman patterns and the calculated model of
      SS, it can be proved that the phase transition results from the distorted
      squarate rings. We infer it is the enhancement of pi-stacking that dominates the
      distortion. For comparison, high-pressure Raman spectra of sodium squarate
      trihydrate (Na(2)C(4)O(4)?3H(2)O, SST) are also investigated. The structure of
      SST is determined by both face-to-face pi-stacking and hydrogen bonding. SST can
      be regarded as a deformation of SS. A phase transition, with the similar
      mechanism as SS, is observed at ~10.3 GPa. Our results can be well supported by
      the previous high-pressure studies of ammonium squarate ((NH(4))(2)C(4)O(4), AS),
      and vice versa. High-pressure behaviors of the noncovalent interactions in SS,
      SST, and AS are compared to show the impacts of hydrogen bonding and the role of
      electrostatic interaction in releasing process.

PMID- 23163393
TI  - Peptide salt bridge stability: from gas phase via microhydration to bulk water
      simulations.
AB  - The salt bridge formation and stability in the terminated lysine-glutamate
      dipeptide is investigated in water clusters of increasing size up to the limit of
      bulk water. Proton transfer dynamics between the acidic and basic side chains is
      described by DFT-based Born-Oppenheimer molecular dynamics simulations. While the
      desolvated peptide prefers to be in its neutral state, already the addition of a
      single water molecule can trigger proton transfer from the glutamate side chain
      to the lysine side chain, leading to a zwitterionic salt bridge state. Upon
      adding more water molecules we find that stabilization of the zwitterionic state
      critically depends on the number of hydrogen bonds between side chain termini,
      the water molecules, and the peptidic backbone. Employing classical molecular
      dynamics simulations for larger clusters, we observed that the salt bridge is
      weakened upon additional hydration. Consequently, long-lived solvent shared ion
      pairs are observed for about 30 water molecules while solvent separated ion pairs
      are found when at least 40 or more water molecules hydrate the dipeptide. These
      results have implications for the formation and stability of salt bridges at
      partially dehydrated surfaces of aqueous proteins.

PMID- 23163394
TI  - Simulating protein unfolding under pressure with a coarse-grained model.
AB  - We describe and test a coarse-grained molecular model for the simulation of the
      effects of pressure on the folding/unfolding transition of proteins. The model is
      a structure-based one, which takes into account the desolvation barrier for the
      formation of the native contacts. The pressure is taken into account in a
      qualitative, mean field approach, acting on the parameters describing the native
      stabilizing interactions. The model has been tested by simulating the
      thermodynamic and structural behavior of protein GB1 with a parallel tempering
      Monte Carlo algorithm. At low effective pressures, the model reproduces the
      standard two-state thermal transition between the native and denatured states.
      However, at large pressures a new state appears. Its structural characteristics
      have been analyzed, showing that it corresponds to a swollen version of the
      native structure. This swollen state is at equilibrium with the native state at
      low temperatures, but gradually transforms into the thermally denatured state as
      temperature is increased. Therefore, our model predicts a downhill transition
      between the swollen and the denatured states. The analysis of the model permits
      us to obtain a phase diagram for the pressure-temperature behavior of the
      simulated system, which is compatible with the known elliptical shape of this
      diagram for real proteins.

PMID- 23163395
TI  - Does catch and release affect the mating system and individual reproductive
      success of wild Atlantic salmon (Salmo salar L.)?
AB  - In this study, we documented the breeding system of a wild population of Atlantic
      salmon (Salmo salar L.) by genetically sampling every returning adult and
      assessed the determinants of individual fitness. We then quantified the impacts
      of catch and release (C&R) on mating and reproductive success. Both sexes showed
      high variance in individual reproductive success, and the estimated standardized
      variance was higher for males (2.86) than for females (0.73). We found a weak
      positive relationship between body size and fitness and observed that fitness was
      positively correlated with the number of mates, especially in males. Mature male
      parr sired 44% of the analysed offspring. The impact of C&R on the number of
      offspring was size dependent, as the reproductive success of larger fish was more
      impaired than smaller ones. Also, there was an interactive negative effect of
      water temperature and air exposure time on reproductive success of C&R salmon.
      This study improves our understanding of the complex reproductive biology of the
      Atlantic salmon and is the first to investigate the impact of C&R on reproductive
      success. Our study expands the management toolbox of appropriate C&R practices
      that promote conservation of salmon populations and limit negative impacts on
      mating and reproductive success.

PMID- 23163396
TI  - Healthcare professional surveys to investigate the implementation of the
      isotretinoin Pregnancy Prevention Programme: a descriptive study.
AB  - OBJECTIVE: Three online surveys explored compliance with the PPP by pharmacists
      and dermatologists, in the Netherlands. In 2007 and 2011, two pharmacist surveys
      were conducted to assess improvement over time. METHODS: In 2007, survey was sent
      to members of the Utrecht Pharmacy Panel for Education & Research (UPPER) network
      (n = 1000) and in 2011, to the research group of the Dutch Association of
      Pharmacists (KNMP) (n = 556). In 2010, a survey was sent to 564 dermatologists of
      the Dutch Association of Dermatology and Venereology (NVDV). RESULTS: Both
      pharmacists' questionnaires had response rates of 20% and the dermatologist
      questionnaire of 28%. Pharmacists' checks on 30-day dispensing remained 82%, but
      a check whether the prescription is out-of-date decreased (61 to 53%).
      Pharmacists asked the patient for a negative pregnancy test in 15%, but use of
      contraception was checked by 44 - 49%. One hundred and five dermatologists (64%)
      always prescribe contraception; 35 (22%) occasionally. Ninety-three percent of
      the dermatologists were of the opinion that they performed the PPP. Analysis of
      different elements of the PPP showed that 41 (25%) were compliant. CONCLUSIONS:
      The observed non-adherence to the isotretinoin PPP calls for careful evaluation
      of risk minimisation plans and participation of all stakeholders in the
      development of these plans.

PMID- 23163397
TI  - Cell stretching measurement utilizing viscoelastic particle focusing.
AB  - We present an efficient method for measuring cell stretching based on three
      dimensional viscoelastic particle focusing. We suspended cells in a biocompatible
      viscoelastic medium [poly(vinylpyrrolidone) solution in phosphate-buffered
      saline]. The medium viscoelasticity significantly homogenized the trajectories of
      cells along the centerline of a simple straight channel, which could not be
      achieved in conventional Newtonian media. More than 95% of red blood cells (RBCs)
      were successfully delivered to the stagnation point of a cross-slot microchannel
      and stretched by extensional flow. By computational simulations, we proved that
      this method prevents inaccuracies due to random lateral distributions of cells
      and, further, guarantees rotational-free cell stretching along the shear-free
      channel centerline. As a demonstration, we characterized the differences in RBC
      deformabilities among various heat treatments. Furthermore, we monitored the
      decrease of deformability due to nutrient starvation in human mesenchymal stem
      cells. We envisage that our novel method can be extended to versatile
      applications such as the detection of pathophysiological evolution in impaired
      RBCs due to malaria or diabetes and the monitoring of cell quality in stem cell
      therapeutics.

PMID- 23163398
TI  - Long-term effects of transcatheter closure of atrial septal defect on cardiac
      remodeling and exercise capacity in patients older than 40 years with a reduction
      in cardiopulmonary function.
AB  - BACKGROUND: Although it has been demonstrated that cardiac remodeling and
      exercise capacity improve after transcatheter closure of atrial septal defect
      (ASD), little is known about long-term benefits in middle-aged and elderly
      patients with a reduction in cardiopulmonary function. OBJECTIVES: To evaluate
      long-term extent and time course of improvements in cardiac remodeling and
      exercise capacity in those patients. METHODS: Twenty ASD patients >= 40 years of
      age with a reduction in cardiopulmonary function (predicted peak oxygen uptake
      [VO(2)] < 65%) were enrolled. Transthoracic echocardiography and cardiopulmonary
      exercise testing were performed at baseline and at 1 month, 3 months, 6 months,
      and >12 months after the procedure. RESULTS: At 1 month after the procedure,
      significant decreases in right ventricular (RV) end-diastolic diameter (38.2 +/-
      4.4 to 31.9 +/- 4.4 mm; P < 0.001) and RV/left ventricular end-diastolic diameter
      ratio (0.95 +/- 0.17 to 0.71 +/- 0.13; P < 0.001) occurred, and they were
      maintained during the follow-up period. Normal RV size was achieved in 11 of 18
      patients with RV enlargement. Predicted peak VO(2) did not change at 1 month and
      3 months, but it improved significantly after 6 months (53.6 +/- 6.5 to 62.1 +/-
      12.6%; P < 0.01). Sixteen of the 20 patients showed improved predicted peak
      VO(2). CONCLUSIONS: Cardiac remodeling and exercise capacity could be improved
      over the long-term period after transcatheter closure of ASD in middle-aged and
      elderly patients with a reduction in cardiopulmonary function. There were
      differences in the time course of improvement between cardiac remodeling and
      exercise capacity in those patients.

PMID- 23163399
TI  - Nongenetic inheritance and the evolution of costly female preference.
AB  - In species where males provide neither direct benefits nor paternal care, it is
      typically assumed that female preferences are maintained by indirect selection
      reflecting genetic benefits to offspring of preferred males. However, it remains
      unclear whether populations harbour sufficient genetic variation in fitness to
      support costly female preferences - a problem called the 'lek paradox'. Here, we
      ask whether indirect selection on female preferences can be maintained by
      nongenetic inheritance. We construct a general model that can be used to
      represent either genetic or nongenetic inheritance, depending on the choice of
      parameter values. Interestingly, we find that costly preference is most likely to
      evolve and persist when fitness depends on an environmentally induced factor that
      can be transmitted over a single generation only, such as an environment
      dependent paternal effect. Costly preference can also be supported when fitness
      depends on a highly mutable factor that can persist over multiple generations,
      such as an epigenetic mark, but the necessary conditions are more restrictive.
      Our findings show that nongenetic inheritance provides a plausible hypothesis for
      the maintenance of costly female preferences in species where males provide no
      direct benefits to females. Nongenetic paternal inheritance of fitness can occur
      in species lacking conventional forms of paternal care. Indeed, transmission of
      paternal condition via sperm-borne nongenetic factors may be more likely to
      evolve than conventional forms of paternal investment because sperm-borne effects
      are protected from cuckoldry. Our results furnish a novel example of an
      interaction between genetic and nongenetic inheritance that can lead to otherwise
      unexpected evolutionary outcomes.

PMID- 23163400
TI  - The CYP3A4*22 allele affects the predictive value of a pharmacogenetic algorithm
      predicting tacrolimus predose concentrations.

PMID- 23163401
TI  - A systematic approach for development of an OPLS-like force field and its
      application to hydrofluorocarbons.
AB  - A systematic, formal approach to optimization of force field parameters for
      molecular simulations is presented. The procedure is based on response surface
      mapping methodology that allows simultaneous parameter optimization against
      multiple property targets while constraining the number of required
      computationally expensive numerical experiments. The approach was implemented for
      prediction of vapor-liquid equilibrium properties of alkanes, alkenes, and their
      fluorinated derivatives via Monte Carlo molecular simulations. To further reduce
      computational costs, a bootstrap procedure that involves a sequence of parameter
      optimization for four pairs of compounds (ethane and propane, ethene and propene,
      perfluoroethane and perfluoropropane, and 2,3,3,3-tetrafluoropropene and (E)
      1,3,3,3-tetrafluoropropene) was used. The results of simulations utilizing the
      optimized force field parameters agree well with associated reference equations
      of state.

PMID- 23163402
TI  - Integrated onshore-offshore investigation of a Mediterranean layered coastal
      aquifer.
AB  - Most of the Mediterranean coastal porous aquifers are intensively exploited.
      Because of climatic and anthropogenic effects, understanding the physical and
      geological controls on groundwater distribution and flow dynamics in such
      aquifers is crucial. This study presents the results of a structural
      investigation of a system located along the coastline of the Gulf of Lions (NW
      Mediterranean). A key aspect of this study relies on an onshore-offshore
      integrated approach combining outcrops, seismic profiles, and borehole data
      analysis. This multidisciplinary approach provides constraints on pore-fluid
      salinity distribution and stratigraphic organization, which are crucial in
      assessing the modes of groundwater/seawater exchanges. Onshore, Lower Pliocene
      deposits dip gently seaward. They are unconformably overlain by Holocene clays in
      the lagoons. Offshore the Pliocene deposits either outcrop at the seabed or are
      buried below nonconsolidated sands infilling paleo-valleys. Beneath the lido, the
      groundwater salinity distribution consists of salty pore water, overlying fresher
      pore water. Active circulation of groundwater masses is inferred from the
      geophysical results. In particular, offshore outcrops and paleo-valleys may play
      an important role in salt water intrusion. 

PMID- 23163403
TI  - 2-O-(3-Hydroxyhexadecanoyl)glycerol and 2-O-(3-hydroxytetradecanoyl)glycerol and
      their 1-O-acetyl derivatives from the glandular trichome exudate of Verbascum
      blattaria f. erubescens.
AB  - Chemical investigation of the glandular trichome exudate of Verbascum blattaria
      f. erubescens (Scrophulariaceae) led to the isolation of four new glycerides, 1-O
      acetyl-2-O-[(R)-3-hydroxytetradecanoyl]-sn-glycerol, 1-O-acetyl-2-O-[(R)-3
      hydroxyhexadecanoyl]-sn-glycerol, 2-O-[(R)-3-hydroxytetradecanoyl]glycerol and 2
      O-[(R)-3-hydroxyhexadecanoyl]glycerol. Their structures, including the
      configurations at the stereogenic centres, were elucidated from spectral evidence
      and chemical transformations.

PMID- 23163404
TI  - Bioferment residue: TG-FTIR study and cocombustion in a MSW incineration plant.
AB  - With fast development of industry large quantities of hazardous waste are
      produced in China. Today, incineration plays an important role in the disposal of
      hazardous waste. Co-incineration of some types of hazardous wastes with municipal
      solid waste (MSW) has been suggested in the Proposed Standards for Pollutants for
      MSW combustors in China, published in 2010. According to this proposal,
      coincinerated hazardous waste should have similar combustion characteristics with
      MSW, such as bioferment residue (HW02-276-001-02 in China Hazardous Waste List).
      In this study, residue from the production of hydrochloride salt spectinomycin, a
      bioferment process, was studied by thermogravimetric analysis (TGA) coupled with
      Fourier transform infrared (TG-FTIR) analysis. In TGA, the sample attains its
      final weight before 800  degrees C. No gaseous pollutants evolve in large amount
      during FTIR analysis. During test runs at a MSW incineration plant in Jinhua,
      Zhejiang Province, bioferment residue was added to MSW at a rate of 24 ton/day
      and fed to the circulated fluidized bed (CFB) incineration system with capacity
      of 500 ton/day MSW. The operating parameters and emissions were monitored. The
      system performance was obviously not affected by addition of bioferment residue
      to MSW/coal and the pollutant emissions met the Chinese standard, with or without
      addition of bioferment into feedstock.

PMID- 23163405
TI  - Emerging role for RNA-based regulation in plant immunity.
AB  - Infection by phytopathogenic bacteria triggers massive changes in plant gene
      expression, which are thought to be mostly a result of transcriptional
      reprogramming. However, evidence is accumulating that plants additionally use
      post-transcriptional regulation of immune-responsive mRNAs as a strategic weapon
      to shape the defense-related transcriptome. Cellular RNA-binding proteins
      regulate RNA stability, splicing or mRNA export of immune-response transcripts.
      In particular, mutants defective in alternative splicing of resistance genes
      exhibit compromised disease resistance. Furthermore, detection of bacterial
      pathogens induces the differential expression of small non-coding RNAs including
      microRNAs that impact the host defense transcriptome. Phytopathogenic bacteria in
      turn have evolved effector proteins to inhibit biogenesis and/or activity of
      cellular microRNAs. Whereas RNA silencing has long been known as an antiviral
      defense response, recent findings also reveal a major role of this process in
      antibacterial defense. Here we review the function of RNA-binding proteins and
      small RNA-directed post-transcriptional regulation in antibacterial defense. We
      mainly focus on studies that used the model system Arabidopsis thaliana and also
      discuss selected examples from other plants.

PMID- 23163406
TI  - Target-specific copper hybrid T7 phage particles.
AB  - Target-specific nanoparticles have attracted significant attention recently, and
      have greatly impacted life and physical sciences as new agents for imaging,
      diagnosis, and therapy, as well as building blocks for the assembly of novel
      complex materials. While most of these particles are synthesized by chemical
      conjugation of an affinity reagent to polymer or inorganic nanoparticles, we are
      promoting the use of phage particles as a carrier to host organic or inorganic
      functional components, as well as to display the affinity reagent on the phage
      surface, taking advantage of the fact that some phages host well-established
      vectors for protein expression. An affinity reagent can be structured in a
      desired geometry on the surface of phage particles, and more importantly, the
      number of the affinity reagent molecules per phage particle can be precisely
      controlled. We previously have reported the use of the T7 phage capsid as a
      template for synthesizing target-specific metal nanoparticles. In this study
      herein, we reported the synthesis of nanoparticles using an intact T7 phage as a
      scaffold from which to extend 415 copies of a peptide that contains a
      hexahistidine (6His) motif for capture of copper ions and staging the conversion
      of copper ions to copper metal, and a cyclic Arginine-Glycine-Aspartic Acid
      (RGD4C) motif for targeting integrin and cancer cells. We demonstrated that the
      recombinant phage could load copper ions under low bulk copper concentrations
      without interfering with its target specificity. Further reduction of copper ions
      to copper metal rendered a very stable copper hybrid T7 phage, which prevents the
      detachment of copper from phage particles and maintains the phage structural
      integrity even under harsh conditions. Cancer cells (MCF-7) can selectively
      uptake copper hybrid T7 phage particles through ligand-mediated transmembrane
      transportation, whereas normal control cells (MCF-12F) uptake 1000-fold less. We
      further demonstrated that copper hybrid T7 phage could be endocytosed by cancer
      cells in culture.

PMID- 23163407
TI  - Cardiac troponin I in congenital heart defects with pressure or volume overload.
AB  - OBJECTIVE: To evaluate the prevalence of cardiac troponin I (cTnI) and
      autoantibodies to cTn in children with congenital heart defects with volume or
      pressure overload fulfilling the criteria for treatment, and in healthy children.
      DESIGN: The study groups comprised 78 children with volume overload caused by an
      atrial septal defect or a patent ductus arteriosus, and 60 children with pressure
      overload caused by coarctation of the aorta or stenosis of the aortic or the
      pulmonary valve, and 74 healthy controls. Serum levels of natriuretic peptides,
      cTnI, and autoantibodies to cTn were analyzed at baseline, prior to treatment and
      in 64 patients 6 months after treatment. RESULTS: At baseline, one child with
      volume overload, 12 children with pressure overload, and one healthy control had
      positive cTnI. Further analysis of the pressure overload subgroup revealed that
      the children with positive cTnI were younger than those with negative cTnI, and
      had higher levels of natriuretic peptides. The pressure gradient at the
      coarctation site or stenotic valve was higher in those with positive TnI. Six
      months after treatment, 63 of 64 children examined were cTnI negative.
      CONCLUSIONS: The cTnI release is more frequently associated with pressure than
      volume overload which resolves after treatment in most children.

PMID- 23163408
TI  - Symptom index P-value and symptom sensitivity index P-value to determine symptom
      association between apnea and reflux in premature infants at term.
AB  - The current method to determine temporal association (TA) between reflux and
      symptoms is the symptom association probability (SAP), but this method has
      limitations due to the constraints of binning and the violation of statistical
      principles of the Fisher's exact test that lead to an invalid estimation of TA.
      The aim of this study is to develop improved methods of computing the TA between
      apneic and reflux events using simulation and permutation methods and to compare
      these to the SAP. TA was analyzed between polysomnographic obstructive apneas and
      multichannel intraluminal impedance (MII) reflux events. Three new numerical
      methods were compared to the SAP in four former premature infants with persistent
      apneas at term. The experimentally found association was compared to the
      association observed in simulated or permuted data consistent with the lack of
      association beyond what is expected by chance alone. Temporal association was
      computed based on symptom and symptom sensitivity indices, SI and SSI, with
      varying window of association (WA) times from 15 to 300 s. The three new methods
      estimated P-values at varying WA that generally followed the same pattern of the
      SAP which had a more erratic pattern. The WA that gave the lowest P-value was
      approximately 120 s. Each of the novel methods produced P-value results
      consistent with each other and the SAP yet not subject to its limitations. The
      variation of WA gave a temporal profile of TA providing clues to its etiology.
      These new metrics are called Symptom Index (SIP) and Symptom Sensitivity Index
      (SSIP) P-values.

PMID- 23163409
TI  - The influence of lifelong musicianship on neurophysiological measures of
      concurrent sound segregation.
AB  - The ability to separate concurrent sounds based on periodicity cues is critical
      for parsing complex auditory scenes. This ability is enhanced in young adult
      musicians and reduced in older adults. Here, we investigated the impact of
      lifelong musicianship on concurrent sound segregation and perception using scalp
      recorded ERPs. Older and younger musicians and nonmusicians were presented with
      periodic harmonic complexes where the second harmonic could be tuned or mistuned
      by 1-16% of its original value. The likelihood of perceiving two simultaneous
      sounds increased with mistuning, and musicians, both older and younger, were more
      likely to detect and report hearing two sounds when the second harmonic was
      mistuned at or above 2%. The perception of a mistuned harmonic as a separate
      sound was paralleled by an object-related negativity that was larger and earlier
      in younger musicians compared with the other three groups. When listeners made a
      judgment about the harmonic stimuli, the perception of the mistuned harmonic as a
      separate sound was paralleled by a positive wave at about 400 msec poststimulus
      (P400), which was enhanced in both older and younger musicians. These findings
      suggest attention-dependent processing of a mistuned harmonic is enhanced in
      older musicians and provides further evidence that age-related decline in hearing
      abilities are mitigated by musical training.

PMID- 23163411
TI  - Habit and nonhabit systems for unconscious and conscious behavior: implications
      for multitasking.
AB  - The study of human consciousness has demonstrated that there are both conscious
      and unconscious systems. Other work, particularly in animals, has shown that
      there are habit and nonhabit systems and that these involve different brain
      regions and memory processes. Here we argue that habits can be equated with
      unconscious behavior and nonhabits with conscious behavior. This equation makes
      the extensive physiological literature on habit/nonhabit relevant to the less
      tractable issue of consciousness. On the basis of this line of reasoning, it
      appears that different parts of the BG and different memory structures mediate
      conscious and unconscious processes. It is further argued here that the
      unconscious system is highly capable; it can both process sensory information and
      produce behavior. The benefit of such a dual system is multitasking: The
      unconscious system can execute background tasks, leaving the conscious system to
      perform more difficult tasks.

PMID- 23163410
TI  - Dissociating N400 effects of prediction from association in single-word contexts.
AB  - When a word is preceded by a supportive context such as a semantically associated
      word or a strongly constraining sentence frame, the N400 component of the ERP is
      reduced in amplitude. An ongoing debate is the degree to which this reduction
      reflects a passive spread of activation across long-term semantic memory
      representations as opposed to specific predictions about upcoming input. We
      addressed this question by embedding semantically associated prime-target pairs
      within an experimental context that encouraged prediction to a greater or lesser
      degree. The proportion of related items was used to manipulate the predictive
      validity of the prime for the target while holding semantic association constant.
      A semantic category probe detection task was used to encourage semantic
      processing and to preclude the need for a motor response on the trials of
      interest. A larger N400 reduction to associated targets was observed in the high
      than the low relatedness proportion condition, consistent with the hypothesis
      that predictions about upcoming stimuli make a substantial contribution to the
      N400 effect. We also observed an earlier priming effect (205-240 msec) in the
      high-proportion condition, which may reflect facilitation because of form-based
      prediction. In summary, the results suggest that predictability modulates N400
      amplitude to a greater degree than the semantic content of the context.

PMID- 23163412
TI  - Meaningful family relationships: neurocognitive buffers of adolescent risk
      taking.
AB  - Discordant development of brain regions responsible for cognitive control and
      reward processing may render adolescents susceptible to risk taking. Identifying
      ways to reduce this neural imbalance during adolescence can have important
      implications for risk taking and associated health outcomes. Accordingly, we
      sought to examine how a key family relationship-family obligation-can reduce this
      vulnerability. Forty-eight adolescents underwent an fMRI scan during which they
      completed a risk-taking and cognitive control task. Results suggest that
      adolescents with greater family obligation values show decreased activation in
      the ventral striatum when receiving monetary rewards and increased dorsolateral
      PFC activation during behavioral inhibition. Reduced ventral striatum activation
      correlated with less real-life risk-taking behavior and enhanced dorsolateral PFC
      activation correlated with better decision-making skills. Thus, family obligation
      may decrease reward sensitivity and enhance cognitive control, thereby reducing
      risk-taking behaviors.

PMID- 23163413
TI  - Repetition suppression in auditory-motor regions to pitch and temporal structure
      in music.
AB  - Music performance requires control of two sequential structures: the ordering of
      pitches and the temporal intervals between successive pitches. Whether pitch and
      temporal structures are processed as separate or integrated features remains
      unclear. A repetition suppression paradigm compared neural and behavioral
      correlates of mapping pitch sequences and temporal sequences to motor movements
      in music performance. Fourteen pianists listened to and performed novel melodies
      on an MR-compatible piano keyboard during fMRI scanning. The pitch or temporal
      patterns in the melodies either changed or repeated (remained the same) across
      consecutive trials. We expected decreased neural response to the patterns (pitch
      or temporal) that repeated across trials relative to patterns that changed. Pitch
      and temporal accuracy were high, and pitch accuracy improved when either pitch or
      temporal sequences repeated over trials. Repetition of either pitch or temporal
      sequences was associated with linear BOLD decrease in frontal-parietal brain
      regions including dorsal and ventral premotor cortex, pre-SMA, and superior
      parietal cortex. Pitch sequence repetition (in contrast to temporal sequence
      repetition) was associated with linear BOLD decrease in the intraparietal sulcus
      (IPS) while pianists listened to melodies they were about to perform. Decreased
      BOLD response in IPS also predicted increase in pitch accuracy only when pitch
      sequences repeated. Thus, behavioral performance and neural response in
      sensorimotor mapping networks were sensitive to both pitch and temporal
      structure, suggesting that pitch and temporal structure are largely integrated in
      auditory-motor transformations. IPS may be involved in transforming pitch
      sequences into spatial coordinates for accurate piano performance.

PMID- 23163414
TI  - Semantic and perceptual processing of number symbols: evidence from a cross
      linguistic fMRI adaptation study.
AB  - The ability to process the numerical magnitude of sets of items has been
      characterized in many animal species. Neuroimaging data have associated this
      ability to represent nonsymbolic numerical magnitudes (e.g., arrays of dots) with
      activity in the bilateral parietal lobes. Yet the quantitative abilities of
      humans are not limited to processing the numerical magnitude of nonsymbolic sets.
      Humans have used this quantitative sense as the foundation for symbolic systems
      for the representation of numerical magnitude. Although numerical symbol use is
      widespread in human cultures, the brain regions involved in processing of
      numerical symbols are just beginning to be understood. Here, we investigated the
      brain regions underlying the semantic and perceptual processing of numerical
      symbols. Specifically, we used an fMRI adaptation paradigm to examine the neural
      response to Hindu-Arabic numerals and Chinese numerical ideographs in a group of
      Chinese readers who could read both symbol types and a control group who could
      read only the numerals. Across groups, the Hindu-Arabic numerals exhibited ratio
      dependent modulation in the left IPS. In contrast, numerical ideographs were
      associated with activation in the right IPS, exclusively in the Chinese readers.
      Furthermore, processing of the visual similarity of both digits and ideographs
      was associated with activation of the left fusiform gyrus. Using culture as an
      independent variable, we provide clear evidence for differences in the brain
      regions associated with the semantic and perceptual processing of numerical
      symbols. Additionally, we reveal a striking difference in the laterality of
      parietal activation between the semantic processing of the two symbols types.

PMID- 23163415
TI  - Unconscious processing of unattended features in human visual cortex.
AB  - Unconscious processing has been convincingly demonstrated for task-relevant
      feature dimensions. However, it is possible that the visual system is capable of
      more complex unconscious operations, extracting visual features even when they
      are unattended and task irrelevant. In the current study, we addressed this
      question by measuring unconscious priming using a task in which human
      participants attended to a target object's shape while ignoring its color. We
      measured both behavioral priming effects and priming-related fMRI activations
      from primes that were unconsciously presented using metacontrast masking. The
      results showed faster RTs and decreases in fMRI activation only when the primes
      were identical to the targets, indicating that primes were processed both in the
      attended shape and the unattended color dimensions. Reductions in activation were
      observed in early visual areas, including primary visual cortex, as well as in
      feature-responsive areas for shape and color. These results indicate that
      multiple features can be unconsciously encoded and possibly bound using the same
      visual networks activated by consciously perceived images.

PMID- 23163416
TI  - Imaging fatigue of interference control reveals the neural basis of executive
      resource depletion.
AB  - Executive control coordinates, prioritizes, and selects task-relevant
      representations under conditions of conflict. Behavioral evidence has documented
      that executive resources are separable, finite, and can be temporarily depleted;
      however, the neural basis for such resource limits are largely unknown. Here, we
      investigate the neural correlates underlying the fatigue or depletion of
      interference control, an executive process hypothesized to mediate competition
      among candidate memory representations. Using a pre/post continuous acquisition
      fMRI design, we demonstrate that, compared with a nondepletion control group, the
      depletion group showed a fatigue-induced performance deficit that was specific to
      interference control and accompanied by a left-to-right shift in the network of
      active regions. Specifically, we observed decreased BOLD signal in the left
      inferior frontal gyrus (IFG), striatum, and the cerebellum, along with a
      corresponding increase in right hemisphere regions including the IFG, insular,
      and temporal cortex. Depletion-related changes in activation magnitude correlated
      with behavioral changes, suggesting that decreased recruitment of task-relevant
      regions, including left IFG, contributes to impaired interference control. These
      results provide new evidence about the brain dynamics of "process-specific"
      fatigue and suggest that depletion may pose a significant limitation on the
      cognitive and neural resources available for executive control.

PMID- 23163417
TI  - Enhanced striatal sensitivity to aversive reinforcement in adolescents versus
      adults.
AB  - Neurodevelopmental changes in mesolimbic regions are associated with adolescent
      risk-taking behavior. Numerous studies have shown exaggerated activation in the
      striatum in adolescents compared with children and adults during reward
      processing. However, striatal sensitivity to aversion remains elusive. Given the
      important role of the striatum in tracking both appetitive and aversive events,
      addressing this question is critical to understanding adolescent decision-making,
      as both positive and negative factors contribute to this behavior. In this study,
      human adult and adolescent participants performed a task in which they received
      squirts of appetitive or aversive liquid while undergoing fMRI, a novel approach
      in human adolescents. Compared with adults, adolescents showed greater behavioral
      and striatal sensitivity to both appetitive and aversive stimuli, an effect that
      was exaggerated in response to delivery of the aversive stimulus. Collectively,
      these findings contribute to understanding how neural responses to positive and
      negative outcomes differ between adolescents and adults and how they may
      influence adolescent behavior.

PMID- 23163418
TI  - Dopamine D2 receptor modulation of human response inhibition and error awareness.
AB  - Response inhibition, comprising action cancellation and action restraint, and
      error awareness are executive functions of considerable clinical relevance to
      neuropsychiatric disorders. Nevertheless, our understanding of their underlying
      catecholamine mechanisms, particularly regarding dopamine, is limited. Here, we
      used the dopamine D2 agonist cabergoline to study its ability to improve
      inhibitory control and modulate awareness of performance errors. A randomized,
      double-blind, placebo-controlled, crossover design with a single dose of
      cabergoline (1.25 mg) and placebo (dextrose) was employed in 25 healthy
      participants. They each performed the stop-signal task, a well-validated measure
      of action cancellation, and the Error Awareness Task, a go/no-go measure of
      action restraint and error awareness, under each drug condition. Cabergoline was
      able to selectively reduce stop-signal RT, compared with placebo, indicative of
      enhanced action cancellation (p < .05). This enhancement occurred without
      concomitant changes in overall response speed or RT variability and was not seen
      for errors of commission on the Error Awareness Task. Awareness of performance
      errors on the go/no-go task was, however, significantly improved by cabergoline
      compared with placebo (p < .05). Our results contribute to growing evidence for
      the dopaminergic control of distinct aspects of human executive ability, namely,
      action cancellation and error awareness. The findings may aid the development of
      new, or the repurposing of existing, pharmacotherapy that targets the cognitive
      dysfunction of psychiatric and neurological disorders. They also provide further
      evidence that specific cognitive paradigms have correspondingly specific
      neurochemical bases.

PMID- 23163419
TI  - Integration of error agency and representation of others' pain in the anterior
      insula.
AB  - A crucial feature of socially adaptive behavior is the ability to recognize when
      our actions harm other individuals. Previous research demonstrates that dorsal
      mediofrontal cortex (dMFC) and anterior insula (AI) are involved in both action
      monitoring and empathy for pain. Here, we tested whether these regions could
      integrate monitoring of error agency with the representation of others' pain.
      While undergoing event-related fMRI, participants played a visual task in turns
      with a friend placed outside the scanner, who would receive painful stimulation
      in half of the error trials. Brain activity was enhanced in dMFC and AI for
      painful compared with nonpainful errors. Left AI and dorsolateral pFC also
      exhibited a significant interaction with agency and increased responses when
      painful errors were caused by oneself. We conclude that AI is crucial for
      integrating inferences about others' feeling states with information about action
      agency and outcome, thus generating an affective signal that may guide subsequent
      adjustment.

PMID- 23163420
TI  - Interacting cortical and basal ganglia networks underlying finding and tapping to
      the musical beat.
AB  - Humans are able to find and tap to the beat of musical rhythms varying in
      complexity from children's songs to modern jazz. Musical beat has no one-to-one
      relationship with auditory features-it is an abstract perceptual representation
      that emerges from the interaction between sensory cues and higher-level cognitive
      organization. Previous investigations have examined the neural basis of beat
      processing but have not tested the core phenomenon of finding and tapping to the
      musical beat. To test this, we used fMRI and had musicians find and tap to the
      beat of rhythms that varied from metrically simple to metrically complex-thus
      from a strong to a weak beat. Unlike most previous studies, we measured beat
      tapping performance during scanning and controlled for possible effects of
      scanner noise on beat perception. Results showed that beat finding and tapping
      recruited largely overlapping brain regions, including the superior temporal
      gyrus (STG), premotor cortex, and ventrolateral PFC (VLPFC). Beat tapping
      activity in STG and VLPFC was correlated with both perception and performance,
      suggesting that they are important for retrieving, selecting, and maintaining the
      musical beat. In contrast BG activity was similar in all conditions and was not
      correlated with either perception or production, suggesting that it may be
      involved in detecting auditory temporal regularity or in associating auditory
      stimuli with a motor response. Importantly, functional connectivity analyses
      showed that these systems interact, indicating that more basic sensorimotor
      mechanisms instantiated in the BG work in tandem with higher-order cognitive
      mechanisms in PFC.

PMID- 23163421
TI  - Critical time course of right frontoparietal involvement in mental number space.
AB  - Neuropsychological, neurophysiological, and neuroimaging studies suggest that
      right frontoparietal circuits may be necessary for the processing of mental
      number space, also known as the mental number line (MNL). Here we sought to
      specify the critical time course of three nodes that have previously been related
      to MNL processing: right posterior parietal cortex (rPPC), right FEF (rFEF), and
      right inferior frontal gyrus (rIFG). The effects of single-pulse TMS delivered at
      120% distance-adjusted individual motor threshold were investigated in 21
      participants, within a window of 0-400 msec (sampling interval = 33 msec) from
      the onset of a central digit (1-9, 5 excluded). Pulses were delivered in a random
      order and with equal probability at each time point, intermixed with noTMS
      trials. To analyze whether and when TMS interfered with MNL processing, we fitted
      bimodal Gaussian functions to the observed data and measured effects on changes
      in the Spatial-Numerical Association of Response Codes (SNARC) effect (i.e., an
      advantage for left- over right-key responses to small numbers and right- over
      left-key responses to large numbers) and in overall performance efficiency. We
      found that, during magnitude judgment with unimanual key-press responses, TMS
      reduced the SNARC effect in the earlier period of the fitted functions (~25-60
      msec) when delivered over rFEF (small and large numbers) and rIFG (small
      numbers); TMS further reduced the SNARC effect for small numbers in a later
      period when delivered to rFEF (~200 msec). In contrast, TMS of rPPC did not
      interfere with the SNARC effect but generally reduced performance for small
      numbers and enhanced it for large numbers, thus producing a pattern reminiscent
      of "neglect" in mental number space. Our results confirm the causal role of an
      intact right frontoparietal network in the processing of mental number space.
      They also indicate that rPPC is specifically tied to explicit number magnitude
      processing and that rFEF and rIFG contribute to interfacing mental visuospatial
      codes with lateralized response codes. Overall, our findings suggest that both
      ventral and dorsal frontoparietal circuits are causally involved and functionally
      connected in the mapping of numbers to space.

PMID- 23163422
TI  - Affective processing in bilingual speakers: disembodied cognition?
AB  - A recent study by Keysar, Hayakawa, and An (2012) suggests that "thinking in a
      foreign language" may reduce decision biases because a foreign language provides
      a greater emotional distance than a native tongue. The possibility of such
      "disembodied" cognition is of great interest for theories of affect and cognition
      and for many other areas of psychological theory and practice, from clinical and
      forensic psychology to marketing, but first this claim needs to be properly
      evaluated. The purpose of this review is to examine the findings of clinical,
      introspective, cognitive, psychophysiological, and neuroimaging studies of
      affective processing in bilingual speakers in order to identify converging
      patterns of results, to evaluate the claim about "disembodied cognition," and to
      outline directions for future inquiry. The findings to date reveal two
      interrelated processing effects. First-language (L1) advantage refers to
      increased automaticity of affective processing in the L1 and heightened
      electrodermal reactivity to L1 emotion-laden words. Second-language (L2)
      advantage refers to decreased automaticity of affective processing in the L2,
      which reduces interference effects and lowers electrodermal reactivity to
      negative emotional stimuli. The differences in L1 and L2 affective processing
      suggest that in some bilingual speakers, in particular late bilinguals and
      foreign language users, respective languages may be differentially embodied, with
      the later learned language processed semantically but not affectively. This
      difference accounts for the reduction of framing biases in L2 processing in the
      study by Keysar et al. (2012). The follow-up discussion identifies the limits of
      the findings to date in terms of participant populations, levels of processing,
      and types of stimuli, puts forth alternative explanations of the documented
      effects, and articulates predictions to be tested in future research.

PMID- 23163425
TI  - Effect of allyl sulfides from garlic essential oil on intracellular ca2+ levels
      in renal tubular cells.
AB  - Diallyl sulfide (1), diallyl disulfide (2), and diallyl trisulfide (3), which are
      major organosulfur compounds of garlic (Allium sativum), are recognized as a
      group of potential chemopreventive compounds. In this study, the early signaling
      effects of 3 were examined on Madin-Darby canine kidney (MDCK) cells loaded with
      the Ca(2+)-sensitive dye fura-2. It was found that 3 caused an immediate and
      sustained increase of [Ca(2+)](i) in a concentration-dependent manner (EC(50) =
      40 MUM). Compound 3 also induced a [Ca(2+)](i) elevation when extracellular
      Ca(2+) was removed, but the magnitude was reduced by 45%. In Ca(2+)-free medium,
      the 3-induced [Ca(2+)](i) level was abolished by depleting stored Ca(2+) with 1
      MUM thapsigargin (an endoplasmic reticulum Ca(2+) pump inhibitor). Elevation of
      [Ca(2+)](i) caused by 3 in the Ca(2+)-containing medium was not affected by
      modulation of protein kinase C activity. The 3-induced Ca(2+) influx was
      inhibited by nifedipine and nicardipine (1 MUM). U73122, an inhibitor of
      phospholipase C, abolished ATP (but not the 3-induced [Ca(2+)](i) level). These
      findings suggest that 3 induced a significant [Ca(2+)](i) elevation in MDCK renal
      tubular cells by stimulating both extracellular Ca(2+) influx and thapsigargin
      sensitive intracellular Ca(2+) release via as yet unidentified mechanisms.
      Furthermore, the order of the allyl sulfide-induced [Ca(2+)](i) elevation and
      cell viability was 1 < 2 < 3. The differential effect of allyl sulfides on Ca(2+)
      signaling and cell death appears to correlate with the number of sulfur atoms in
      the structure of these allyl sulfides.

PMID- 23163426
TI  - Purtscher-like retinopathy related to drug-induced hypersensitivity syndrome.
AB  - PURPOSE: To report a case with Purtscher-like retinopathy related to drug-induced
      hypersensitivity syndrome (DIHS). DESIGN: Case report. METHODS: A 31-year-old
      male with fever, macula-papular rash, lymphadenopathy, and hepatitis was
      hospitalized. RESULTS: Eosinophilic leukocytosis, as well as cotton wool spots
      around the optic disc, was observed. Viral, bacteriologic, and parasitologic
      tests and rheumatologic markers were all negative. Given his history of
      antibiotic use, he was diagnosed as DIHS. On the seventh day he lost
      consciousness and and on the tenth day he died. CONCLUSION: Purtscher-like
      retinopathy might be a sign of DIHS, and should be considered in the differential
      diagnosis where early intervention is needed.

PMID- 23163427
TI  - Characterization of a potentially novel 'blown pack' spoilage bacterium isolated
      from bovine hide.
AB  - AIMS: To characterize a psychrotrophic bacterium, designated TC1, previously
      isolated from a cattle hide in Ireland, and to investigate the ability of this
      strain to cause 'blown pack' spoilage (BPS) of vacuum-packaged beef primals.
      METHODS AND RESULTS: TC1 was characterized using a combination of phenotypic,
      chemotaxonomic and genotypic analyses and was assessed for its ability to spoil
      vacuum-packaged beef at refrigerated temperatures. TC1 was Gram-positive and
      formed elliptical subterminal endospores. The strain was able to grow between 0
      and 33  degrees C, with optimal growth between 23 and 24  degrees C. TC1 could be
      differentiated from its phylogenetically closest neighbour (Clostridium
      lituseburense DSM 797(T)) by 16S rRNA gene sequencing, pulsed-field gel
      electrophoresis and cellular fatty acid composition. TC1 spoiled (BPS) beef
      within 42 days when inoculated in cold-stored (1  degrees C) vacuum-packed beef.
      CONCLUSIONS: The phenotypic, chemotaxonomic and genotypic characterization
      indicated that TC1 may represent a potentially novel, cold-tolerant, gas
      producing bacterium of considerable economic significance to the beef industry.
      SIGNIFICANCE AND IMPACT OF THE STUDY: This study reports and characterizes an
      emerging BPS bacterium, which should be considered in future activities designed
      to minimize the psychrophilic and psychrotrophic spoilage of vacuum-packaged
      beef.

PMID- 23163428
TI  - Anticoagulants, renal failure and atrial fibrillation.
AB  - The prevalence of atrial fibrillation (AF) in patients with chronic renal failure
      (CRF) and end-stage renal disease (ESRD) is very high and also in this population
      AF is associated with an increased risk of stroke. Warfarin is the treatment of
      choice for AF to prevent thromboembolic events, but it has been reported that its
      use in CRF and hemodialysis (HD) patients is associated with an increased risk of
      bleeding compared with patients with normal renal function. Moreover, historical
      studies suggest that warfarin increases the incidence of both ischemic and
      hemorrhagic strokes in HD patients. However, a clear benefit:risk ratio against
      warfarin in patients with CRF or ESRD and AF has not been demonstrated. New oral
      anticoagulants, thrombin or factor Xa inhibitors, are now available. Patients
      with severe CRF (i.e., glomerular filtration rate < 30 mL/min) and with ESRD,
      however, were excluded from the trials that have established their efficacy and
      safety. The advent of new oral anticoagulants raises the important question if
      patients with severe CRF and ESRD should be excluded or not from this new
      therapeutic opportunity.

PMID- 23163429
TI  - A question of time: the land snail Murella muralis (Gastropoda: Pulmonata)
      reveals constraints on past ecological speciation.
AB  - The lively debate about speciation currently focuses on the relative importance
      of factors driving population differentiation. While many studies are
      increasingly producing results on the importance of selection, little is known
      about the interaction between drift and selection. Moreover, there is still
      little knowledge on the spatial-temporal scales at which speciation occurs, that
      is, arrangement of habitat patches, abruptness of habitat transitions, climate
      and habitat changes interacting with selective forces. To investigate these
      questions, we quantified variation on a fine geographical scale analysing
      morphological (shell) and genetic data sets coupled with environmental data in
      the land snail Murella muralis, endemic to the Mediterranean island of Sicily.
      Analysis of a fragment of the mitochondrial DNA cytochrome oxidase I gene (COI)
      and eight nuclear microsatellite loci showed that genetic variation is highly
      structured at a very fine spatial scale by local palaeogeographical events and
      historical population dynamics. Molecular clock estimates, calibrated here
      specifically for Tyrrhenian land snails, provided a framework of
      palaeogeographical events responsible for the observed geographical variations
      and migration routes. Finally, we showed for the first time well-documented lines
      of evidence of selection in the past, which explains divergence of land snail
      shell shapes. We suggest that time and palaeogeographical history acted as
      constraints in the progress along the ecological speciation continuum. Our study
      shows that testing for correlation among palaeogeography, morphology and genetic
      data on a fine geographical scale provides information fundamental for a detailed
      understanding of ecological speciation processes.

PMID- 23163430
TI  - Effective targeting of Abeta to macrophages by sonochemically prepared surface
      modified protein microspheres.
AB  - Imbalanced homeostasis and oligomerization of the amyloid-beta (Abeta) peptide in
      the brain are hallmarks of Alzheimer's disease (AD). Microglia and macrophages
      play a critical role in the etiology of AD either by clearing Abeta from the
      brain or inducing inflammation. Recent evidence suggests that clearance of Abeta
      by microglia/macrophages via the phagocytic pathway is defective in AD, which can
      contribute to the accumulation of Abeta in the brain. We have recently
      demonstrated that protein microspheres modified at their surface with multiple
      copies of an Abeta-recognition motif can strongly bind Abeta, inhibit its
      aggregation, and directly reduce its toxicity by sequestering it from the medium.
      Here, we describe how microsphere-bound Abeta can stimulate microglial cells and
      be phagocytosed through a mechanism that is distinct from that of Abeta removal
      and, thus, contribute to the clearance of Abeta, even by defective microglial
      cells. The phagocytosis was most effective, with microspheres having a diameter
      of <1 MUm. The introduction of polyethylene glycol to the surface of the
      microspheres changed the kinetics of the phagocytosis. Moreover, while aggregated
      Abeta induced a significant inflammatory response that was manifested by the
      release of TNF-alpha, the microsphere-bound Abeta dramatically reduced the amount
      of cytokine released from microglial cells.

PMID- 23163431
TI  - Achieving the millennium development goal of reducing maternal mortality in rural
      Africa: an experience from Burundi.
AB  - OBJECTIVES: To estimate the reduction in maternal mortality associated with the
      emergency obstetric care provided by Medecins Sans Frontieres (MSF) and to
      compare this to the fifth Millennium Development Goal of reducing maternal
      mortality. METHODS: The impact of MSF's intervention was approximated by
      estimating how many deaths were averted among women transferred to and treated at
      MSF's emergency obstetric care facility in Kabezi, Burundi, with a severe acute
      maternal morbidity. Using this estimate, the resulting theoretical maternal
      mortality ratio in Kabezi was calculated and compared to the Millennium
      Development Goal for Burundi. RESULTS: In 2011, 1385 women from Kabezi were
      transferred to the MSF facility, of whom 55% had a severe acute maternal
      morbidity. We estimated that the MSF intervention averted 74% (range 55-99%) of
      maternal deaths in Kabezi district, equating to a district maternal mortality
      rate of 208 (range 8-360) deaths/100,000 live births. This lies very near to the
      2015 MDG 5 target for Burundi (285 deaths/100,000 live births). CONCLUSION:
      Provision of quality emergency obstetric care combined with a functional patient
      transfer system can be associated with a rapid and substantial reduction in
      maternal mortality, and may thus be a possible way to achieve Millennium
      Development Goal 5 in rural Africa.

PMID- 23163433
TI  - Edward F. Diener: Award for Distinguished Scientific Contributions.
AB  - Presents Edward F. Diener as one of the winners of the American Psychological
      Association's Award for Distinguished Scientific Contributions (2012). Edward F.
      Diener has been a leader in every aspect of well-being research. He provided an
      influential conception of well-being as consisting of cognitive and emotional
      elements. A citation, biography, and selected bibliography are presented here.

PMID- 23163434
TI  - New findings and future directions for subjective well-being research.
AB  - Recent findings on subjective well-being (SWB) are presented, and I describe the
      important questions for future research that these raise. Worldwide predictors of
      SWB such as social support and fulfillment of basic needs have been uncovered,
      and there are large differences in SWB between societies. A number of culture
      specific predictors of SWB have also been found. Research on social comparison
      suggests that a world standard for a desirable income has developed. New findings
      on adaptation indicate that habituation to conditions is not always complete and
      that circumstances in some cases can have a large and lasting effect on SWB. An
      important finding is that high SWB benefits health, longevity, citizenship, and
      social relationships. Because of the benefits of SWB as well as the strong
      effects societal conditions can have on it, I proposed national accounts of SWB,
      which are now being seriously considered by nations. Finally, I review advances
      in methodology that are needed to move beyond conclusions based on simple cross
      sectional correlations based on global self-report scales. Each of the findings
      raises new and important questions for future research.

PMID- 23163435
TI  - Michael J. Meaney: Award for Distinguished Scientific Contributions.
AB  - Presents Michael J. Meaney as one of the winners of the American Psychological
      Association's Award for Distinguished Scientific Contributions (2012). Michael J.
      Meaney has taken the phenomenon of 'handling' of newborn rats and opened a new
      area of investigation that has given new meaning to epigenetics via his work
      demonstrating transgenerational behavioral transmission to offspring of
      exploratory, nurturing, and anxiety-related behaviors. He has also used this
      model to demonstrate reversible, early-life epigenetic modifications of genes in
      the infant brain by DNA methylation that affect gene expression and that lead to
      behavioral characteristics in response to stressors that can last throughout the
      life span. His studies have also shown a pathway for translation of these
      processes to the human condition and, in so doing, have inspired a new generation
      of basic and translational research on gene-environment interactions in early
      life that affect the brain and behavior. A citation, biography, and selected
      bibliography are presented here.

PMID- 23163436
TI  - Daniel L. Schacter: Award for Distinguished Scientific Contributions.
AB  - Presents Daniel L. Schacter as one of the winners of the American Psychological
      Association's Award for Distinguished Scientific Contributions (2012). Daniel L.
      Schacter's major theoretical and empirical contributions include groundbreaking
      research on the psychological and neural foundations of implicit and explicit
      memory, memory distortions and errors, and prospective episodic thought. He has
      propelled the field of cognitive neuroscience, first through studies of patients
      suffering anterograde amnesia and subsequently through functional brain imaging
      studies. A citation, biography, and selected bibliography are presented here.

PMID- 23163438
TI  - Mindsets and human nature: promoting change in the Middle East, the schoolyard,
      the racial divide, and willpower.
AB  - Debates about human nature often revolve around what is built in. However, the
      hallmark of human nature is how much of a person's identity is not built in;
      rather, it is humans' great capacity to adapt, change, and grow. This nature
      versus nurture debate matters-not only to students of human nature-but to
      everyone. It matters whether people believe that their core qualities are fixed
      by nature (an entity theory, or fixed mindset) or whether they believe that their
      qualities can be developed (an incremental theory, or growth mindset). In this
      article, I show that an emphasis on growth not only increases intellectual
      achievement but can also advance conflict resolution between long-standing
      adversaries, decrease even chronic aggression, foster cross-race relations, and
      enhance willpower. I close by returning to human nature and considering how it is
      best conceptualized and studied.

PMID- 23163437
TI  - Adaptive constructive processes and the future of memory.
AB  - Memory serves critical functions in everyday life but is also prone to error.
      This article examines adaptive constructive processes, which play a functional
      role in memory and cognition but can also produce distortions, errors, and
      illusions. The article describes several types of memory errors that are produced
      by adaptive constructive processes and focuses in particular on the process of
      imagining or simulating events that might occur in one's personal future.
      Simulating future events relies on many of the same cognitive and neural
      processes as remembering past events, which may help to explain why imagination
      and memory can be easily confused. The article considers both pitfalls and
      adaptive aspects of future event simulation in the context of research on
      planning, prediction, problem solving, mind-wandering, prospective and
      retrospective memory, coping and positivity bias, and the interconnected set of
      brain regions known as the default network.

PMID- 23163440
TI  - Kelly D. Brownell: Award for Distinguished Scientific Applications of Psychology.
AB  - Presents a short biography of Kelly D. Brownwell, winner of the American
      Psychological Association's Award for Distinguished Scientific Applications of
      Psychology (2012). He won the award for outstanding contributions to our
      understanding of the etiology and management of obesity and the crisis it poses
      for the modern world. A seminal thinker in the field, Kelly D. Brownell has been
      a persuasive proponent of the view that the surge in obesity is attributable to a
      'toxic food environment' that includes easy access to abundant but energy-dense
      and aggressively marketed food. An exemplary leader, he has inspired students and
      colleagues alike through his tenacious advocacy of the social and behavioral
      sciences in the public interest. Brownwell's Award citation and a selected
      bibliography are also presented here. (PsycINFO Database Record (c) 2012 APA, all
      rights reserved).

PMID- 23163442
TI  - Thomas L. Griffiths: Award for Distinguished Scientific Early Career
      Contributions to Psychology.
AB  - Presents a short biography of one of the winners of the American Psychological
      Association's Award for Distinguished Scientific Early Career Contributions to
      Psychology (2012). Thomas L. Griffiths won the award for bringing mathematical
      precision to the deepest questions in human learning, reasoning, and concept
      formation. In his pioneering work, Thomas L. Griffiths has used probabilistic
      models and Bayesian learning methods to illuminate an extraordinarily wide range
      of problems in areas including causal reasoning, high-level hierarchical
      thinking, cultural evolution, theory formation, and cognitive development while
      also showing that thinking probabilistically can provide a genuine resolution of
      the age-old tension between nativism and empiricism. His rigorous mathematical
      and computational abilities are accompanied by an immensely creative imagination,
      a sure sense of the important problem, and an unerring touch for the right
      experiment. Griffith's Award citation and a selected biblography are also
      presented here.

PMID- 23163443
TI  - Angela J. Grippo: Award for Distinguished Scientific Early Career Contributions
      to Psychology.
AB  - Presents a short biography of one of the winners of the American Psychological
      Association's Award for Distinguished Scientific Early Career Contributions to
      Psychology. The 2012 winner is Angela J. Grippo for her creative contributions in
      investigating the association between depression and cardiovascular disease in
      preclinical animal models. Using sophisticated behavioral and neuroscience
      methods, Grippo found changes in sympathetic tone, immune system activation, and
      serotonin levels, as well as increased susceptibility to life-threatening
      arrhythmias, in a rodent model of depression, changes similar to those observed
      in humans with depression and heart disease. Her research illustrates how animal
      models of physiology and behavior advance understanding of the connections among
      depression, stress, and physical disease in humans. Grippo's Award citation and a
      selected bibliography are also presented here.

PMID- 23163444
TI  - Bob McMurray: Award for Distinguished Scientific Early Career Contributions to
      Psychology.
AB  - Presents a short biography of one of the winners of the American Psychological
      Association's Award for Distinguished Scientific Early Career Contributions to
      Psychology. The 2012 winner is Bob McMurray for pioneering research on speech and
      language processing in infants and adults. McMurray has conducted influential
      work on the graded nature of speech categories, demonstrating within-category
      sensitivity in the service of efficient processing and optimal cue integration
      during online comprehension. He has also applied a rigorous computational
      approach to learning and development, revealing the emergence of stable
      categories in the face of extraneous variability and the rapid growth of
      childhood vocabulary within the context of a parallel dynamic system. Finally, he
      has developed innovative eye-tracking methods to study category learning in
      normal infants and adults as well as the time course of language processing in
      special populations. McMurray's Award citation and a selected biblography are
      also presented here.

PMID- 23163445
TI  - Friederike Range: Award for Distinguished Scientific Early Career Contributions
      to Psychology.
AB  - Presents a short biography of one of the winners of the American Psychological
      Association's Award for Distinguished Scientific Early Career Contributions to
      Psychology. The 2012 winner is Friederike Range for outstanding contributions to
      the understanding of the complex social minds of nonhuman animals. Through
      ingenious experimental approaches, Range has opened windows into the social
      cognition of monkeys, ravens, dogs, and wolves. With dogs, she was the first to
      apply the touch screen paradigm, and she has conducted groundbreaking studies on
      selective imitation and inequity avoidance. By co-founding new research
      facilities, such as the Clever Dog Lab and the Wolf Science Center, she has
      created novel opportunities for future scientific developments and for a new
      generation of young researchers. Range's Award citation and a selected
      bibliography are also presented here.

PMID- 23163446
TI  - Laurie R. Santos: Award for Distinguished Scientific Early Career Contributions
      to Psychology.
AB  - Presents a short biography of one of the winners of the American Psychological
      Association's Award for Distinguished Scientific Early Career Contributions to
      Psychology. The 2012 winner is Laurie R. Santos for creative and insightful
      investigations of cognition across a broad range of species and psychological
      domains, illuminating cognitive development and cognitive evolution. Laurie R.
      Santos links many branches of psychological inquiry in her research, including
      animal behavior, comparative psychology, developmental psychology, judgment and
      decision making, and social psychology. In particular, her studies of biases,
      irrationalities, and errors- where rational decision making fails, rather than
      succeeds-are providing remarkable insights into how cognitive biases evolved and
      how decision making operates at a fundamental level. Her accomplishments
      beautifully illustrate the power of comparative studies of animal learning and
      behavior to help us understand the human mind. Santos' Award citation and a
      selected bibliography are also presented here.

PMID- 23163447
TI  - Bethany Ann Teachman: Award for Distinguished Scientific Early Career
      Contributions to Psychology.
AB  - Presents a short biography of one of the winners of the American Psychological
      Association's Award for Distinguished Scientific Early Career Contributions to
      Psychology. The 2012 winner is Bethany Ann Teachman for transformative,
      translational research integrating social cognition, life-span, and perceptual
      approaches to investigating clinical phenomena both in the lab and over the
      course of treatment in unique and externally valid ways. Using elegant and
      incisive methods, Teachman has identified cognitive processes that contribute to
      the development and maintenance of fear and anxiety disorders, especially
      thinking that occurs outside of conscious control. Her work shows the critical
      need to consider the role of automatic processing of emotional information in
      order to understand, for example, the seemingly irrational cognitions that
      accompany panic attacks in otherwise highly rational individuals.

PMID- 23163449
TI  - Bernice Lott: Award for Distinguished Senior Career Contributions to Psychology
      in the Public Interest.
AB  - Presents a short biography of the winner of the American Psychological
      Association's Award for Distinguished Senior Career Contributions to Psychology
      in the Public Interest. The 2012 winner is Bernice Lott. Lott's commitment to the
      public interest has always guided her career, as her groundbreaking research on
      gender, ethnicity, and race demonstrates. Her leadership on issues of economic
      injustice paved the way for attention to little-explored dimensions of
      psychology's social justice agenda: classism and poverty. She was a catalyst for
      APA initiatives such as the Resolution on Poverty and Socioeconomic Status, and
      she was instrumental in the establishment of APA's Committee on Socioeconomic
      Status. Thanks to Lott's vision, APA has a formal structure that
      institutionalizes poverty-related work as well as a brilliant body of scholarship
      to inform those efforts. Lott's Award citation and a selected bibliography are
      also presented.

PMID- 23163450
TI  - The social psychology of class and classism.
AB  - In the United States, one is born into a family that can be identified as working
      class, middle class, or affluent-divisions that denote status and power, as
      defined by access to resources. This article explores the relationships between
      social class membership and a wide array of personal and social daily life
      experiences. It concludes with a discussion of classism, which contributes to
      diminished opportunities for low-income families.

PMID- 23163451
TI  - Marguerita Lightfoot: Award for Distinguished Senior Career Contributions to
      Psychology in the Public Interest.
AB  - Presents a short biography of the winner of the American Psychological
      Association's Award for Distinguished Early Career Contributions to Psychology in
      the Public Interest. The 2012 winner is Marguerita Lightfoot for her leadership,
      innovation, and commitment to applying psychological principles to develop
      behavioral health interventions for vulnerable populations, particularly homeless
      adolescents and racial/ethnic groups. Lightfoot's professional career has been
      dedicated to addressing the HIV/AIDS epidemic both in the United States and
      Africa. She pioneered the use of computer-based interventions based on rigorous
      psychological principles, including the innovation of using text messaging and
      web-based social networking forums to deliver prevention messages to youth. She
      is dedicated to mentoring students and new researchers as well as working hand in
      hand with the communities she serves in order to effect change. Lightfoot's Award
      citation and a selected bibliography are also presented here.

PMID- 23163452
TI  - HIV prevention for adolescents: where do we go from here?
AB  - The World Health Organization estimates that 50% of the 30 million HIV infections
      worldwide occurred in young people between the ages of 15 and 24 years. In the
      United States, national statistics estimate that almost 40% of new HIV cases
      occur in youth ages 13-29 (Centers for Disease Control and Prevention, 2011).
      Therefore, a focus on preventing HIV/AIDS among adolescents and young adults is
      warranted. There has been success in developing efficacious interventions for
      adolescents that reduce HIV sexual risk behaviors; however, the HIV incidence
      rates among adolescents remain alarming. This article identifies four areas of
      intervention development that remain underdeveloped and may guide the next
      generation of HIV prevention interventions. Family-based interventions,
      addressing health disparities and understanding the social determinants of health
      for adolescents, expanding the theoretical models that are relied on in
      developing interventions, and utilization of new technologies each have promise
      for successfully assisting adolescents to reduce their risk behaviors and enhance
      protective factors.

PMID- 23163454
TI  - Dan Olweus: Award for Distinguished Contributions to Research in Public Policy.
AB  - Presents a short biography of the winner of the American Psychological
      Association's Award for Distinguished Contributions to Research in Public Policy.
      The 2012 winner is Dan Olweus for his rigorous scientific research on bullying
      among children and youth and his early and tireless attention to its public
      policy implications. Dan Olweus's research on the nature, prevalence, and
      consequences of bullying and his work to develop and disseminate an evidence
      based prevention program provide a model of excellence in the field. His work has
      played a vital role in the dramatic changes that have occurred in many countries
      in recent years-from viewing bullying as a normative and accepted part of life at
      school to recognizing bullying as a pressing public health issue. Olweus's Award
      citation and a selected bibliography are also presented.

PMID- 23163456
TI  - W. Gregory Keilin: Award for Distinguished Contributions to Education and
      Training in Psychology.
AB  - Presents a short biography of the 2012 winner of the American Psychological
      Association's Award for Distinguished Contributions to Education and Training in
      Psychology. W. Gregory Keilin has spent the majority of his professional career
      providing training and administration for psychology doctoral internship programs
      as well as leadership service for psychology internship training. He has been
      engaged in writing innovative training materials and has been passionate in his
      leadership in promoting some of the most important networks of communications for
      education and training: He was instrumental in developing the Association of
      Psychology Postdoctoral and Internship Centers (APPIC) Clearinghouse and in
      improving the APPIC Internship Match Program. Keilin's Award citation and a
      selected bibliography are also presented.

PMID- 23163458
TI  - C. Cybele Raver: Award for Distinguished Contributions of Applications of
      Psychology to Education and Training.
AB  - Presents a short biography of the 2012 winner of the American Psychological
      Association's Award for Distinguished Contributions of Applications of Psychology
      to Education and Training. C. Cybele Raver is a prolific and award-winning writer
      who has published widely and served as a reviewer on many high-quality journals.
      Her publications are well cited, and she has received support from numerous
      foundations and federal sources. One of the most highly respected scholars and
      investigators in developmental science, she studies the various factors that
      affect children's self-regulation and consequently their academic readiness. Her
      research has revealed effective new strategies for prevention and intervention at
      home and at school for the most educationally and economically challenged
      children. Raver's Award citation and a selected bibliography are also presented.

PMID- 23163461
TI  - Cynthia J. Najdowski: Psi Chi/APA Edwin B. Newman Graduate Research Award.
AB  - Presents a short biography of the winner of the American Psychological
      Association's Psi Chi/APA Edwin B. Newman Graduate Research Award. The 2012
      winner is Cynthia J. Najdowski for an outstanding research paper that examines
      how jurors' judgments are influenced by a juvenile defendant's confession and
      status as intellectually disabled. Through the use of a mock trial experiment,
      the research revealed that jurors discounted a juvenile's coerced confession and
      sometimes used intellectual disability as a mitigating factor. Attribution theory
      and the discounting principle were used to identify the psychological mechanisms
      underlying this effect. The paper, titled 'Understanding Jurors' Judgments in
      Cases Involving Juvenile Defendants,' was published in Psychology, Public Policy,
      and Law in October 2011 and was the basis for Najdowski's selection as the
      recipient of the 2012 Psi Chi/APA Edwin B. Newman Graduate Research Award. Bette
      L. Bottoms, PhD, served as faculty supervisor. Najdowski's Award citation and a
      selected bibliography are also presented.

PMID- 23163459
TI  - Low-income children's self-regulation in the classroom: scientific inquiry for
      social change.
AB  - Over 21% of children in the United States today are poor, and the income gap
      between our nation's richest and poorest children has widened dramatically over
      time. This article considers children's self-regulation as a key mediating
      mechanism through which poverty has deleterious consequences for their later life
      outcomes. Evidence from field experiments suggests that low-income children's
      self-regulation is modifiable by early educational intervention, offering a
      powerful policy option for reducing poverty's negative impact. The author
      discusses ways that scientific models of self-regulation can be expanded to
      include multiple developmental periods and real-world classroom contexts.
      Recommendations for advances in research design, measurement, and analysis are
      discussed, as are implications for policy formation and evaluation.

PMID- 23163463
TI  - Leslie S. Greenberg: Award for Distinguished Professional Contributions to
      Applied Research.
AB  - Presents a short biography of the 2012 winner of the American Psychological
      Association's Award for Distinguished Professional Contributions to Applied
      Research. Leslie S. Greenberg is an exemplary scientist-practitioner whose
      pioneering work has significantly altered the landscape of the field of
      psychotherapy research and practice. His seminal research program has addressed
      basic questions regarding the significance of empathy, the therapeutic alliance,
      and emotion in human functioning. Greenberg's sophisticated task-analytic
      research method, used to empirically test processes of change occurring within
      psychotherapy, has allowed researchers to build models of how people in
      individual therapy resolve self-criticism, let go of unresolved anger and hurt
      from past emotional injuries, and resolve conflict in marital therapy. Greenberg
      has made a substantial impact through the development of a new therapeutic
      approach called emotion-focused therapy, an evidence-based treatment for both
      depression and couples' distress. Greenberg's Award citation and a selected
      bibliography are also presented here.

PMID- 23163464
TI  - Emotions, the great captains of our lives: their role in the process of change in
      psychotherapy.
AB  - A view of human functioning is presented in which functioning is seen as
      integrating head and heart, emotion and reason, in a process by which people are
      constantly making sense of their lived emotional experience to form narratives of
      told experience. Because much of the processing involved in the generation of
      emotional experience occurs independently of and prior to conscious thought,
      therapeutic work on a purely cognitive level of processing is unlikely to produce
      enduring emotional change. The questions especially relevant to psychotherapy are
      how we can best facilitate change in emotions rather than only changes in
      cognition or behavior. A theory of emotional change is presented in which change
      in emotion is seen as requiring that first emotions be felt and then they both be
      exposed to new emotional experience and be reflected on to create new meaning.
      The process of emotional change thus involves both new experience and new
      understanding. At times, people also need to protect themselves from being
      overwhelmed by emotions. They need to be helped to tolerate and regulate them so
      that emotions inform their lives rather than control them. The importance of both
      emotion awareness and emotion regulation in therapeutic change is thus
      highlighted. The article ends by reviewing research on the role of emotional
      processing in therapeutic change and presents six empirically based principles of
      emotional processing that will help move the field toward psychotherapy
      integration in a manner that clearly recognizes emotion as a key component of
      functioning and change.

PMID- 23163466
TI  - Sandra L. Shullman: Award for Distinguished Professional Contributions to
      Independent Practice.
AB  - Presents a short biography of the winner of the American psychological
      Association's Award for Distinguished Professional Contributions to Independent
      Practice. The 2012 winner is Sandra L. Shullman for her outstanding contributions
      and leadership as an independent practitioner in the fields of counseling and
      consulting psychology. Through her national scholarship on sexual harassment in
      the workplace, her development of the practice of organizational counseling
      psychology, her management of a leading behavioral health care practice, and her
      pioneering leadership development initiatives for national and international
      clients, Shullman has greatly enhanced the public's recognition of psychology. In
      addition, her involvement and leadership as a representative of independent
      practitioners in professional associations at the state and national levels have
      benefited the profession in immeasurable ways. Shullman's Award citation and a
      selected bibliography are also presented here.

PMID- 23163468
TI  - Michael E. Barnes: Award for Distinguished Professional Contributions to
      Institutional Practice.
AB  - Presents a short biography on the winner of the American Psychological
      Association's Award for Distinguished Professional Contributions to Institutional
      Practice. The 2012 winner is Michael E. Barnes for his pioneering leadership,
      dedication, and distinguished contributions to juvenile justice. As chief
      psychologist of the Superior Court of the District of Columbia's Child Guidance
      Clinic, Barnes and his staff have provided exceptional psychological service to
      thousands of adjudicated youths, developed an APA-accredited internship program,
      and supervised the development of a juvenile mental health court that diverts
      mentally ill court-involved youth from delinquency proceedings and into
      treatment.

PMID- 23163470
TI  - Melissa L. Anderson: APA/APAGS Award for Distinguished Graduate Student in
      Professional Psychology.
AB  - Presents a short biography of the winner of the American Psychological
      Association/American Psychological Association of Graduate Students Award for
      Distinguished Graduate Student in Professional Psychology. The 2012 winner is
      Melissa L. Anderson for her ongoing commitment to understanding, treating, and
      preventing domestic violence in Deaf women and underserved populations in
      general. Anderson is passionate in her efforts to study the factors underlying
      violence toward women and in applying psychological science to intervene in and
      prevent such abuse. She is dedicated to improving the quality of life and well
      being of underserved women and ensuring that services and programs become
      accessible to them. Anderson's Award citation is also presented.

PMID- 23163472
TI  - Fanny M. Cheung: Award for Distinguished Contributions to the International
      Advancement of Psychology.
AB  - Presents a short biography of one of the co-recipients of the American
      Psychological Association's Award for Distinguished Contributions to the
      International Advancement of Psychology. One of the 2012 winners is Fanny M.
      Cheung for her outstanding contributions to the assessment of cross-cultural
      psychopathology, personality psychology, and gender issues, as well as her
      longstanding efforts in support of the development and advancement of psychology
      in Asia. Cheung has been a pioneer of international psychology. While leading the
      effort to standardize the Chinese MMPI, and as the president of the International
      Test Commission, she has advocated for best practices in cross-cultural
      assessment. By adopting a combined emic-etic approach to developing the Chinese
      Personality Assessment Inventory, the first Asian personality measure translated
      into six other languages, she overcame the ethnocentricism found in both the etic
      and emic approaches. As the current editor of the Asian Journal of Social
      Psychology and in her 20-year involvement in the International Association of
      Applied Psychology, she has facilitated mutual support for international
      psychologists and fostered their voices in mainstream psychology.

PMID- 23163473
TI  - Mainstreaming culture in psychology.
AB  - Despite the "awakening" to the importance of culture in psychology in America,
      international psychology has remained on the sidelines of psychological science.
      The author recounts her personal and professional experience in tandem with the
      stages of development in international/cross-cultural psychology. Based on her
      research in cross-cultural personality assessment, the author discusses the
      inadequacies of sole reliance on either the etic or the emic approach and points
      out the advantages of a combined emic-etic approach in bridging global and local
      human experiences in psychological science and practice. With the blurring of the
      boundaries between North American-European psychologies and psychology in the
      rest of the world, there is a need to mainstream culture in psychology's
      epistemological paradigm. Borrowing from the concept of gender mainstreaming that
      embraces both similarities and differences in promoting equal opportunities, the
      author discusses the parallel needs of acknowledging universals and specifics
      when mainstreaming culture in psychology. She calls for building a culturally
      informed universal knowledge base that should be incorporated in the psychology
      curriculum and textbooks.

PMID- 23163474
TI  - Daniel Landis: Award for Distinguished Contributions to the International
      Advancement of Psychology.
AB  - Presents a short biography of one of the co-recipients of the American
      Psychological Association's Award for Distinguished Contributions to the
      International Advancement of Psychology. One of the 2012 winners is Daniel Landis
      for his unparalleled contribution to the field of intercultural research in a
      distinguished academic career spanning almost half a century. Landis has shaped
      the field of intercultural research through scholarship of the highest order,
      reflected in his publications on cross-cultural training and research, the
      measurement of equal opportunity climate, individual-differences research and
      methodology, evaluation of social programs, development of theory in social
      psychology, and cross-cultural aspects of human sexuality. He is the founding
      editor-in-chief of the International Journal of Intercultural Relations and has
      edited three editions of the Handbook of Intercultural Training (1983, 1996,
      2004). Landis' Award citation and a selected bibliography are also presented.

PMID- 23163476
TI  - John W. Thoburn: International Humanitarian Award.
AB  - Presents a short biography of the winner of the American Psychological
      Association's International Humanitarian Award. The 2012 winner, John W. Thoburn,
      is an extraordinary psychologist who devotes himself consistently to service to
      underserved populations, especially in the aftermath of natural or human-induced
      disasters. He exemplifies a genuine commitment to rapid and meaningful response
      to the most challenging situations. For over 25 years, his dedication has taken
      him to Uganda, Bosnia, India, Sri Lanka, New Orleans, China, and Haiti, at his
      own personal expense and inconvenience. His approach is infused with his
      contextual view that all relevant individuals and systems must be included in
      efforts aimed at improving people's lives. He works in a calm, modest, and often
      humorous manner, and his innate traits of affability and flexibility consistently
      serve him well in his humanitarian efforts. Thoburn's Award citation and a
      selected bibliography are also presented.

PMID- 23163478
TI  - Superstrate CuInS2 photovoltaics with enhanced performance using a CdS/ZnO
      nanorod array.
AB  - An air-stable, low-temperature, solution-based process for preparing CuInS(2)
      (CIS) superstrate solar cells using CdS-decorated ZnO nanorod (NR) arrays is
      reported. Efficient light harvesting and photoexcited charge transport were
      achieved by fabricating a ZnO NR window layer with a large p-n junction area via
      a hydrothermal reaction. A CdS buffer layer was deposited on a transparent ZnO NR
      substrate at room temperature via successive ion layer adsorption and reaction
      (SILAR) or nanocrystal layer deposition (NCLD). The prepared CdS/ZnO NR assembly
      was coated with a CIS absorber layer without the need for surface passivation
      organics or dispersion reagents. The CIS precursor solution, prepared using a
      metal salt, thiourea, and an amine solvent, yielded CIS nanocrystals (NCs) at
      temperatures up to 250  degrees C. The CIS/CdS/ZnO NR heterojunction structure
      exhibited an excellent photovoltaic performance compared to a planar ZnO film
      device due to enhanced light transmittance toward the absorber and a high charge
      collection efficiency. These results suggest that a superstrate CIS/CdS/ZnO NRs
      photovoltaic cell fabricated via the low-cost route described here has great
      potential as a next-generation solar cell device.

PMID- 23163479
TI  - Molecular dynamics studies of fluid/oil interfaces for improved oil recovery
      processes.
AB  - In our paper, we study the interface wettability, diffusivity, and molecular
      orientation between crude oil and different fluids for applications in improved
      oil recovery (IOR) processes through atomistic molecular dynamics (MD). The salt
      concentration, temperature, and pressure effects on the physical chemistry
      properties of different interfaces between IOR agents [brine (H(2)O + % NaCl),
      CO(2), N(2), and CH(4)] and crude oil have been determined. From the interfacial
      density profiles, an accumulation of aromatic molecules near the interface has
      been observed. In the case of brine interfaced with crude oil, our calculations
      indicate an increase in the interfacial tension with increasing pressure and salt
      concentration, which favors oil displacement. On the other hand, with the other
      fluids studied (CO(2), N(2), and CH(4)), the interfacial tension decreases with
      increasing pressure and temperature. With interfacial tension reduction, an
      increase in fluid diffusivity in the oil phase is observed. We also studied the
      molecular orientation properties of the hydrocarbon and fluids molecules in the
      interface region. We perceived that the molecular orientation could be affected
      by changes in the interfacial tension and diffusivity of the molecules in the
      interface region with the increased pressure and temperature: pressure
      (increasing) -> interfacial tension (decreasing) -> diffusion (increasing) ->
      molecular ordering. From a molecular point of view, the combination of low
      interfacial tension and high diffusion of molecules in the oil phase gives the
      CO(2) molecules unique properties as an IOR fluid compared with other fluids
      studied here.

PMID- 23163477
TI  - Bacterial cell-wall recycling.
AB  - Many Gram-negative and Gram-positive bacteria recycle a significant proportion of
      the peptidoglycan components of their cell walls during their growth and
      septation. In many--and quite possibly all--bacteria, the peptidoglycan fragments
      are recovered and recycled. Although cell-wall recycling is beneficial for the
      recovery of resources, it also serves as a mechanism to detect cell-wall
      targeting antibiotics and to regulate resistance mechanisms. In several Gram
      negative pathogens, anhydro-MurNAc-peptide cell-wall fragments regulate AmpC beta
      lactamase induction. In some Gram-positive organisms, short peptides derived from
      the cell wall regulate the induction of both beta-lactamase and beta-lactam
      resistant penicillin-binding proteins. The involvement of peptidoglycan recycling
      with resistance regulation suggests that inhibitors of the enzymes involved in
      the recycling might synergize with cell-wall-targeted antibiotics. Indeed, such
      inhibitors improve the potency of beta-lactams in vitro against inducible AmpC
      beta-lactamase-producing bacteria. We describe the key steps of cell-wall
      remodeling and recycling, the regulation of resistance mechanisms by cell-wall
      recycling, and recent advances toward the discovery of cell-wall-recycling
      inhibitors.

PMID- 23163481
TI  - Phytochemical analysis and toxicity investigation of stem bark of Scutia
      buxifolia Reissek.
AB  - Phytochemical analysis of lyophilised aqueous extract of the stem bark of Scutia
      buxifolia (SBSB) was carried out by determining total phenolics (0.280 +/- 0.02
      mg of gallic acid equivalents/g of extract), flavonoids (17.42 +/- 2.95 mg of
      quercetin equivalents/g of extract) and tannins (1.28 +/- 0.15 mg of catechin
      equivalents/g of extract) contents followed by a high-performance liquid
      chromatography/diode array detection (HPLC/DAD) analysis. The HPLC profile showed
      caffeic acid, being the major constituent of SBSB (247.21 +/- 2.17 mg g-1 of
      extract). The antioxidant scavenging capacity of SBSB was determined by 2,2
      diphenyl-2-picrylhydrazyl (DPPH) assay. The antioxidant power of SBSB was
      comparable with that of the antioxidant ascorbic acid. Acute toxicity was assayed
      in rats whereas catalase activity and malondialdehyde production were determined
      in rats' liver. The SBSB showed safety in the dose tested. This report is the
      first realised in animals for S. buxifolia.

PMID- 23163480
TI  - Preoperative and intraoperative assessment of myometrial invasion in endometrial
      cancer: comparison of magnetic resonance imaging and frozen sections.
AB  - OBJECTIVE: To compare the diagnostic characteristics of the evaluation of
      myometrial invasion (MI) retrospectively between preoperative magnetic resonance
      imaging (MRI) and intraoperative frozen sections. DESIGN: A retrospective study.
      SETTING: University hospital. SAMPLE: 201 women diagnosed with endometrial
      carcinoma. METHODS: All women underwent preoperative MRI and 111 of them also
      underwent intraoperative frozen section assessment. The final pathological
      evaluation was used as the definitive diagnosis. MAIN OUTCOME MEASURES: In women
      who underwent MRI and frozen sections (n = 111), the accuracies of detection of
      MI and of deep invasion (defined as >=50% invasion) were compared. RESULTS: The
      accuracy, sensitivity, and specificity of MRI for detection of MI were 65.8,
      58.8, and 88.5%, and those in frozen sections were 90.1, 90.6, and 88.5%,
      respectively. The accuracy and sensitivity of frozen sections were significantly
      higher (p < 0.001, p < 0.001), whereas the specificity of the two methods did not
      differ (p = 1.000). The accuracy, sensitivity, and specificity of MRI for
      detection of deep invasion were 83.8, 69.2, and 88.2%, and those of frozen
      sections were 93.7, 73.1, and 100.0%, respectively. The accuracy and specificity
      of frozen sections were significantly higher (p = 0.007 and p < 0.001,
      respectively), whereas sensitivity did not show a significant difference (p =
      0.999). CONCLUSION: In assessment of MI, the accuracy of frozen sections was
      significantly higher than that of MRI. Since the diagnostic characteristics
      differ between two methods, additional intraoperative frozen sections are
      recommended for more accurate assessment of MI when MRI is negative for the
      presence of any MI or positive for the presence of deep invasion.

PMID- 23163482
TI  - Detecting proteins in microfluidic channels decorated with liquid crystal sensing
      dots.
AB  - In this paper, we report the integration of liquid crystal (LC) dots on
      microfluidic channels as microscopic protein sensors. Flexibility of patterning
      LC dots on a surface to fit small microfluidic channels is achieved by using
      inkjet printing technology. These LC dots (1 pL) remain stable when they are
      subjected to flowing buffer solution at a high flow velocity (v >= 0.198 cm/s).
      When the buffer solution contains protein, such as bovine serum albumin (BSA), it
      causes a change in the orientational ordering of the LC dots as indicated by a
      distinct dark-to-bright transition in the optical appearance of the LC dots.
      Moreover, we are able estimate the concentration of BSA by simply counting the
      number of bright LC dot sections. This microscopic protein sensor has potential
      applications in the real-time detection and quantification of proteins in aqueous
      solutions. This detection method is advantageous because protein labeling and
      complex instrumentation are not required.

PMID- 23163483
TI  - Genital divergence in sympatric sister snails.
AB  - A pattern of greater divergence in mating traits between sister-species pairs
      with overlapping ranges than between allopatric species pairs is expected if
      reinforcement commonly contributes to speciation. Few large-scale comparative
      analyses have addressed this prediction, especially for genital form. Here, we
      show that penial morphology follows the predicted pattern in 40 robustly
      identified sister-species pairs in the marine gastropod subfamily Littorininae.
      Further work is needed to exclude other processes that may contribute to genital
      divergence between sympatric species, but the clear pattern we observe strongly
      suggests a role for genital form in reproductive isolation in this large clade.

PMID- 23163484
TI  - Prognostic relevance and therapeutic implications of centromere protein F
      expression in patients with esophageal squamous cell carcinoma.
AB  - Centromere protein F (CENP-F), a cell cycle-regulated centromere protein, has
      been shown to affect numerous tumorigenic processes. This study aimed to clarify
      the prognostic significance of CENP-F expression in patients with esophageal
      squamous cell carcinoma (ESCC). The levels of CENP-F messenger RNA and protein
      were higher in ESCC cell lines than in the normal tissues. An immunohistochemical
      analysis of paired tissue specimens showed that the CENP-F expression was higher
      in tumorous tissues than in the adjacent non-tumorous tissues (P < 0.001).
      Moreover, there was a significant correlation between CENP-F expression and
      gender (P = 0.012), clinical stage (P = 0.039), and T classification (P = 0.026).
      Patients with higher CENP-F expression had shorter overall survival than those
      with lower CENP-F expression (P = 0.009). Multivariate Cox analysis indicated
      that CENP-F expression is an independent prognostic factor for overall survival
      (hazard ratio = 0.582, 95% confidence interval = 0.397-0.804, P = 0.041).
      Importantly, it was found that zoledronic acid (ZOL) could significantly enhance
      the chemotherapeutic sensitivity of ESCC cell lines with high CENP-F expression
      to cisplatin, although ZOL alone only exhibited a minor inhibitory effect to ESCC
      cells. In summary, these findings demonstrate that CENP-F may serve as a valuable
      molecular marker for predicting the prognosis of ESCC patients. In addition, the
      data indicate a potential benefit of combining ZOL with cisplatin in ESCC,
      suggesting that CENP-F expression may have therapeutic implications.

PMID- 23163485
TI  - Electric field modulation of the membrane potential in solid-state ion channels.
AB  - Biological ion channels are molecular devices that allow a rapid flow of ions
      across the cell membrane. Normal physiological functions, such as generating
      action potentials for cell-to-cell communication, are highly dependent on ion
      channels that can open and close in response to external stimuli for regulating
      ion permeation. Mimicking these biological functions using synthetic structures
      is a rapidly progressing yet challenging area. Here we report the electric field
      modulation of the membrane potential phenomena in mechanically and chemically
      robust solid-state ion channels, an abiotic analogue to the voltage-gated ion
      channels in living systems. To understand the complex physicochemical processes
      in the electric field regulated membrane potential behavior, both quasi-static
      and transient characteristics of converting transmembrane ion gradients into
      electric potential are investigated. It is found that the transmembrane potential
      can be adequately tuned by an external electrical stimulation, thanks to the
      unique properties of the voltage-regulated selective ion transport through a
      nanoscale channel.

PMID- 23163486
TI  - Phototransformation rates and mechanisms for synthetic hormone growth promoters
      used in animal agriculture.
AB  - Trenbolone acetate, melengestrol acetate, and zeranol are synthetic hormones
      extensively used as growth promoters in animal agriculture, yet despite
      occurrence in water and soil little is known about their environmental fate.
      Here, we establish the time scales and mechanisms by which these synthetic growth
      promoters and their metabolites (SGPMs) undergo phototransformation in sunlit
      surface waters. The families of trenbolone acetate (including 17beta-trenbolone,
      17alpha-trenbolone, and trendione) and melengestrol acetate (including
      melengestrol) readily undergo direct photolysis, exhibiting half-lives between
      ~0.25 and 1 h in both natural and simulated sunlight that were largely
      insensitive to solution variables (e.g., pH, temperature, and cosolutes). Direct
      photolysis yielded products that not only are more photostable but also maintain
      their steroidal ring structure and therefore may retain some biological activity.
      In contrast, zeranol, beta-zearalanol, and zearalanone only exhibited reactivity
      in irradiated solutions of model humic and fulvic acids, and rates of indirect
      photolysis increased steadily from pH 7 to 9. Use of selective probe and quencher
      compounds suggest hydroxyl radical and triplet state dissolved organic matter are
      responsible for zeranol family decay at neutral pH, although singlet oxygen
      contributes modestly in more alkaline waters. This observed pH-dependence appears
      to result from photooxidants reacting primarily with the monodeprotonated form of
      zeranol (pK(a) values of 8.44 and 11.42). This investigation provides the first
      characterization of the fate of this emerging pollutant class in sunlit surface
      waters and prioritizes future efforts on the identity, fate, and biological
      impact of their more persistent phototransformation products.

PMID- 23163487
TI  - Identity-expression interaction in face perception: sex, visual field, and
      psychophysical factors.
AB  - We investigated the psychophysical factors underlying the identity-emotion
      interaction in face perception. Visual field and sex were also taken into
      account. Participants had to judge whether a probe face, presented in either the
      left or the right visual field, and a central target face belonging to same
      person while emotional expression varied (Experiment 1) or to judge whether probe
      and target faces expressed the same emotion while identity was manipulated
      (Experiment 2). For accuracy we replicated the mutual facilitation effect between
      identity and emotion; no sex or hemispheric differences were found. Processing
      speed measurements, however, showed a lesser degree of interference in women than
      in men, especially for matching identity when faces expressed different emotions
      after a left visual presentation probe face. Psychophysical indices can be used
      to determine whether these effects are perceptual (A') or instead arise at a post
      perceptual decision-making stage (B"). The influence of identity on the
      processing of facial emotion seems to be due to perceptual factors, whereas the
      influence of emotion changes on identity processing seems to be related to
      decisional factors. In addition, men seem to be more "conservative" after a
      LVF/RH probe-face presentation when processing identity. Women seem to benefit
      from better abilities to extract facial invariant aspects relative to identity. 

PMID- 23163488
TI  - Structure modification of montmorillonite nanoclay by surface coating with soy
      protein.
AB  - To achieve exfoliated and/or intercalated structures, montmorillonite (MMT) was
      surface-coated by soy protein at 60  degrees C, at MMT/soy protein powder mass
      ratios of 49:1, 9:1, 4:1, and 2:1 and pH 2.0-10.0. The protein-coated MMT was
      triple-washed and lyophilized for characterization. Protein coating was observed
      at all pH conditions, based on data from X-ray diffraction, Fourier transform
      infrared spectroscopy, zeta potential, and quantification of protein remaining in
      the continuous phase and present in the triple-washed MMT. At a mass ratio of
      4:1, >90% protein bound with MMT, with the largest d-spacing at pH 9.0. When the
      mass ratio was increased to 2:1, protein-coated MMT at pH 9.0 demonstrated the
      highest degree of intercalation/exfoliation, corresponding to disappearance of
      the diffraction peak characteristic of pristine MMT. This study thus demonstrated
      that intercalation/exfoliation of MMT can be easily achieved by coating with low
      cost soy protein for manufacturing nanocomposite materials.

PMID- 23163489
TI  - Evaluation of near-critical overdamping effects in slug-test response.
AB  - A slug test behaves as a harmonic oscillator, subject to both inertial effects
      and viscous damping. When viscous and inertial forces are closely balanced, the
      system is nearly critically damped, and water-level recovery is affected by
      inertial effects, but does not exhibit oscillation. These effects were
      investigated by use of type curves, generated both by modification of Kipp's
      (1985) computer program and by use of the Butler-Zhan (2004) model. Utility of
      the type curves was verified by re-analysis of the Regina slug test previously
      analyzed by Kipp. These type curves indicate that near-critical inertial effects
      result in early-time delayed water-level response followed by merger with, or
      more rapid recovery than, response for the fully damped case. Because of this
      early time response, slug tests in the moderately over-damped range are best
      analyzed using log-log type curves of (1 - H/H(0)) vs. Tt/r(2c). Failure to
      recognize inertial effects in slug test data could result in an over-estimate of
      transmissivity, and a too-small estimate of storage coefficient or too-large
      estimate of well skin. However, application of the widely used but highly
      empirical Hvorslev (1951) method to analyze both the Regina slug test and type
      curve generated data indicate that such analyses provide T values within a factor
      of 2 of the true value.

PMID- 23163490
TI  - Optical coherence tomography evaluation in the Multicenter Uveitis Steroid
      Treatment (MUST) trial.
AB  - PURPOSE: To describe the evaluation of optical coherence tomography (OCT) scans
      in the Muliticenter Uveitis Steroid Treatment (MUST) trial and report baseline
      OCT features of enrolled participants. METHODS: Time-domain OCTs acquired by
      certified photographers using a standardized scan protocol were evaluated at a
      reading center. Accuracy of retinal thickness data was confirmed with quality
      evaluation, and caliper measurement of centerpoint thickness (CPT) was performed
      when retinal thickness data were unreliable. Morphological evaluation included
      cysts, subretinal fluid, epiretinal membranes (ERMs), and vitreomacular traction.
      RESULTS: Of the 453 OCTs evaluated, automated retinal thickness was accurate in
      69.5% of scans, caliper measurement was performed in 26%, and 4% were ungradable.
      Intraclass correlation was.98 for reproducibility of caliper measurement. Macular
      edema (centerpoint thickness >= 240 MUm) was present in 36%. Cysts were present
      in 36.6% of scans and ERMs in 27.8%, predominantly central. Intergrader agreement
      ranged from 78 to 82% for morphological features. CONCLUSION: Retinal thickness
      data can be retrieved in a majority of OCT scans in clinical trial submissions
      for uveitis studies. Small cysts and ERMs involving the center are common in
      intermediate and posterior/panuveitis requiring systemic corticosteroid therapy.

PMID- 23163492
TI  - And so this is Christmas--.

PMID- 23163493
TI  - Denosumab: do we need another of the same?

PMID- 23163494
TI  - Sociocultural and environmental influences on bladder health.

PMID- 23163495
TI  - Frequency and outcomes of painful physical symptoms in a naturalistic population
      with major depressive disorder: an analysis of pooled observational studies
      focusing on subjects aged 65 years and over.
AB  - AIMS: To estimate the frequency of painful physical symptoms (PPS) in elderly
      subjects (>= 65 years) with major depressive disorder (MDD) in real-world
      clinical conditions and to establish whether PPS are associated with poor
      depression outcomes, including more severe depression and worse health-related
      quality of life (HRQoL). METHODS: Observational studies of MDD that included
      assessment of PPS and elderly subjects were screened. Measures of PPS were based
      on the Somatic Symptom Inventory (SSI) or Visual Analogue Scale (VAS). Data from
      a variety of depressive symptom severity and HRQoL scales were used. Analysis
      cohorts were based on age [aged >= 65 years (elderly) or < 65 years (younger)]
      and/or PPS status (presence or absence); five subsets were used to examine
      specific outcomes in matched elderly subjects. RESULTS: Data from seven studies
      (representing 26 countries) were collated. Of the 11,477 subjects, 14% were aged
      >= 65 years and 71% were classified as having PPS (PPS+). PPS were more frequent
      in elderly subjects (74% vs. 70% of younger subjects) and were positively
      associated with being female and Hispanic, and negatively associated with being
      East Asian in the elderly. The presence of PPS was associated with more severe
      clinical symptomatology and comparatively poorer HRQoL in elderly subjects.
      CONCLUSIONS: PPS, although frequent in younger MDD patients, were slightly more
      frequent in elderly MDD patients and associated with comparatively poorer
      clinical and functional outcomes. As elderly patients report somatic symptoms
      more readily than emotional symptoms, physicians should consider depression in
      addition to physical causes when PPS are present.

PMID- 23163496
TI  - Evaluation of diagnostic and prognostic value of clinical characteristics of
      migraine and tension type headache included in the diagnostic criteria for
      children and adolescents in International Classification of Headache Disorders-
      second edition.
AB  - Data about the sensitivity and the specificity of the items included in the
      diagnostic criteria for migraine and tension type headache (TTH) in children is
      limited and sometimes controversial. AIM: To evaluate the diagnostic value of
      characteristics of migraine and TTH included in the diagnostic criteria of ICHD
      II and according to results to suggest additional criteria for diagnostic
      differentiation of primary paediatric headache. PATIENTS AND METHODS: The
      investigation consisted of an epidemiological school-based study (1029 pupils
      completed the study and 412 had chronic or recurrent headache) and a clinical
      study conducted in Paediatric Neurology Ward and outpatient clinic (203 patients
      with chronic or recurrent headache). Inclusion criterion was at least two
      episodes of headache during the last year. Exclusion criteria were: headache
      occurring only during acute infections; withdrawal of informed consent. ICHD - II
      was used to classify headache. The diagnostic value of characteristics of
      migraine and TTH was measured using sensitivity, specificity, odds ratio and area
      under receiver operating characteristic curve (AUC). RESULTS: Regarding the AUC,
      the best diagnostic items for migraine are: moderate or severe intensity or only
      severe intensity, pain aggravation by physical activity, pulsating quality,
      respectively, for TTH - no photophobia, no nausea, no aggravation by physical
      activity, mild or moderate intensity and non-pulsating quality. The most
      significant symptom for increasing the migraine risk was pulsating pain and the
      most significant items for TTH risk were no photophobia, bilateral location and
      no nausea. Family history of migraine also increased migraine risk and could be
      either included in the diagnostic criteria for migraine or recommended as
      additional item in differentiating migraine and TTH with overlapping diagnostic
      criteria. According to AUC, we could recommend changing the content of the item
      of intensity for migraine as only severe intensity.

PMID- 23163497
TI  - Adverse effects of homeopathy: a systematic review of published case reports and
      case series.
AB  - AIM: The aim of this systematic review was to critically evaluate the evidence
      regarding the adverse effects (AEs) of homeopathy. METHOD: Five electronic
      databases were searched to identify all relevant case reports and case series.
      RESULTS: In total, 38 primary reports met our inclusion criteria. Of those, 30
      pertained to direct AEs of homeopathic remedies; and eight were related to AEs
      caused by the substitution of conventional medicine with homeopathy. The total
      number of patients who experienced AEs of homeopathy amounted to 1159. Overall,
      AEs ranged from mild-to-severe and included four fatalities. The most common AEs
      were allergic reactions and intoxications. Rhus toxidendron was the most
      frequently implicated homeopathic remedy. CONCLUSION: Homeopathy has the
      potential to harm patients and consumers in both direct and indirect ways.
      Clinicians should be aware of its risks and advise their patients accordingly.

PMID- 23163491
TI  - Sustaining attention to simple tasks: a meta-analytic review of the neural
      mechanisms of vigilant attention.
AB  - Maintaining attention for more than a few seconds is essential for mastering
      everyday life. Yet, our ability to stay focused on a particular task is limited,
      resulting in well-known performance decrements with increasing time on task.
      Intriguingly, such decrements are even more likely if the task is cognitively
      simple and repetitive. The attentional function that enables our prolonged
      engagement in intellectually unchallenging, uninteresting activities has been
      termed vigilant attention. Here we synthesized what we have learned from
      functional neuroimaging about the mechanisms of this essential mental faculty. To
      this end, a quantitative meta-analysis of pertinent neuroimaging studies was
      performed, including supplementary analyses of moderating factors. Furthermore,
      we reviewed the available evidence on neural time-on-task effects, additionally
      considering information obtained from patients with focal brain damage.
      Integrating the results of both meta-analysis and review, we identified a set of
      mainly right-lateralized brain regions that may form the core network subserving
      vigilant attention in humans, including dorsomedial, mid- and ventrolateral
      prefrontal cortex, anterior insula, parietal areas (intraparietal sulcus,
      temporoparietal junction), and subcortical structures (cerebellar vermis,
      thalamus, putamen, midbrain). We discuss the potential functional roles of
      different nodes of this network as well as implications of our findings for a
      theoretical account of vigilant attention. It is conjectured that sustaining
      attention is a multicomponent, nonunitary mental faculty, involving a mixture of
      (a) sustained/recurrent processes subserving task-set/arousal maintenance and (b)
      transient processes subserving the target-driven reorienting of attention.
      Finally, limitations of previous studies are considered and suggestions for
      future research are provided.

PMID- 23163498
TI  - Systemic bias in the medical literature on androgen deprivation therapy and its
      implication to clinical practice.
AB  - BACKGROUND: LHRH agonists are used for androgen deprivation therapy (ADT) to
      treat prostate cancer, but have many side effects that reduce of the quality of
      life of prostate cancer patients and their partners. Patients are poorly informed
      about the side effects of these drugs and how to manage them. AIM: To test the
      hypothesis that there is bias in the peer-reviewed literature on ADT that
      correlates with an association between authors and the luteinising hormone
      releasing hormone (LHRH) agonists pharmaceutical industry. METHODS: We assessed
      155 articles on ADT published in English-language peer-reviewed journals in terms
      of how comprehensive they were in acknowledging LHRH agonists' side effects.
      RESULTS: Although the literature regarding ADT is substantial, the vast majority
      of articles failed to acknowledge many of the more stressful side effects of ADT
      for patients and their partners. Articles most likely to acknowledge the
      psychosocial impact of ADT were significantly less likely to have had industrial
      support than those articles that did not mention those side effects. Alternative
      treatments to the LHRH agonists were rarely mentioned. Authors who indicated some
      association with a pharmaceutical company tended to minimise the side effects of
      LHRH agonists and not acknowledge alternatives to the LHRH agonists for ADT.
      CONCLUSION: Industrial support is associated with a proliferation of articles
      published in the peer-reviewed literature directed at practising physicians. Such
      flooding of the literature may, in part, limit physicians' knowledge of the side
      effects of these drugs and, in turn, account for the poor knowledge that patients
      on LHRH agonists have about the drugs they are taking and ways to manage their
      side effects.

PMID- 23163499
TI  - Antibiotic use: do parents act differently for their children?
AB  - BACKGROUND: Many children in the community take antibiotics inappropriately.
      Previous studies comparing parents with other adults suggest that parents are
      more judicious with antibiotics for their children. This study aims to explore
      the difference between parents' use of antibiotics for themselves and for their
      children. METHODS: The study adopted a combined qualitative and quantitative
      approach. Eight focus groups were conducted with 56 participants purposively
      recruited from community centres and of different socio-economic strata. The
      qualitative data collected were used to construct a questionnaire for the
      telephone survey, which recruited 2471 adults randomly selected from the local
      household directory, of whom 547 had ever brought their children or grand
      children for medical consultation. RESULTS: Both the qualitative and quantitative
      approaches showed that parents were more cautious with antibiotics for children
      than for themselves. The main reason was their concern of side effects. Fever was
      the most important drive for their desire of antibiotics for children. The
      misconception of antibiotics' effectiveness for sore throat was another
      determinant of the desire. These attitudes and behaviour were not affected by the
      respondents' sex, age, education or household income. CONCLUSION: On the whole,
      parents did to their children what they would do for themselves, but to a lesser
      extent. Parents' better knowledge and attitudes will lead to more appropriate use
      of antibiotics for their children.

PMID- 23163500
TI  - Treatment of obstructive sleep apnoea as a therapeutic modality for associated
      erectile dysfunction.
AB  - AIM: This study aimed to determine the impact of long-term treatment with
      continuous positive airway pressure (CPAP) and obstruction relieving surgical
      procedure on obstructive sleep apnoea syndrome (OSAS) patients on erectile
      function (EF). METHODS: Eighty male OSAS patients, suffering from erectile
      dysfunction (ED) were studied. The severity of OSAS was determined by evaluation
      of daytime sleep tendency using the Epworth Sleepiness Scale (ESS), measure of
      minimal oxygen saturation (SaO(2)) percentage and the frequency of apnoea
      hypopnea index (AHI) during sleep. EFs were assessed using five-question
      International Index of Erectile Function (IIEF-5) questionnaire. The nocturnal
      penile rigidity of the patients was evaluated using automated Rigiscan. RESULTS:
      Patients were subjected to CPAP every night for 3 months. After 3 months of CPAP
      treatment, the patients showed significant improvements in ESS and recorded much
      lower SaO(2) percentages compared with their pre-treatment measures. Moreover,
      post-treatment AHIs were significantly lower, compared with pre-treatment
      indexes. Post-treatment evaluation of EFs showed significant improvements.
      CONCLUSIONS: In summary, OSAS in male patients can be considered as an underlying
      pathogenic factor for later development of ED. Therefore, its treatment can
      induce significant improvement in patients' EF. The mechanism underlying ED in
      patients with OSAS remains unclear. However, nasal CPAP, which is the gold
      standard in treatment of OSAS patients, and obstruction relieving surgery have
      been found effective in improving sexual performance and quality of life.

PMID- 23163502
TI  - Sociodemographic and lifestyle factors affecting the self-perception period of
      lower urinary tract symptoms of international prostate symptom score items.
AB  - AIMS: This study investigated the influence of sociodemographic and lifestyle
      factors on the lower urinary tract symptom (LUTS) self-perception period and
      International Prostate Symptom Score. METHOD: This cross-sectional study examined
      209 men aged >= 40 years with non-treated LUTS who participated in a prostate
      examination survey. Questions included International Prostate Symptom Score
      (IPSS) items with self-perception periods for each item. Sociodemographic and
      lifestyle factors were also assessed. Participants were divided by mild LUTS
      (IPSS less than 8) and moderate-to-severe LUTS (IPSS 8 or higher). RESULTS: Self
      perception period of the moderate-to-severe LUTS (n = 110) was affected by BMI;
      the self-perception period of the mild LUTS (n = 90) was affected by age, income,
      occupation and concomitant disease. Moderate-to-severe LUTS were affected by self
      perception period (p = 0.03). Self-perception period was affected by concern for
      health (p = 0.005) by multivariate analysis, and self-perception period of mild
      LUTS was affected by BMI (p = 0.012). Moderate-to-severe LUTS were affected by
      age, number of family members, concern for health and drinking (p < 0.05,
      respectively) by multivariate analysis. CONCLUSION: Lower urinary tract symptom
      was affected by self-perception period. In moderate-to-severe LUTS, age, concern
      for health and drinking were affecting factors of self-perception period.

PMID- 23163501
TI  - Treatment satisfaction with low-dose tamsulosin for symptomatic benign prostatic
      hyperplasia: results from a multicentre cross-sectional survey.
AB  - AIMS: To evaluate the efficacy and treatment satisfaction with low-dose (0.2 mg)
      tamsulosin in patients with symptomatic benign prostatic hyperplasia (BPH), and
      to investigate individual lower urinary tract symptoms according to treatment
      satisfaction. METHODS: A cross-sectional study was conducted in a total sample of
      2574 patients from multiple centres. International Prostate Symptom Score (IPSS),
      prostate volume, uroflowmetry and combined medications were reviewed. Detailed
      questionnaires were used to assess treatment satisfaction and IPSS 8 weeks after
      treatment with low-dose tamsulosin. RESULTS: After 8 weeks of treatment with low
      dose tamsulosin, IPSS improved significantly. Among the 2574 patients, 1,630
      (63.42%) were satisfied and 940 patients (36.50%) were dissatisfied with low-dose
      tamsulosin. The reasons for dissatisfaction included efficacy problems (84.66%)
      and side effects (3.72%). Treatment satisfaction was affected by symptom
      duration, baseline IPSS, and prostate size (p = 0.0441, < 0.001, < 0.009,
      respectively). IPSS voiding (IPSS-V) and IPSS storage (IPSS-S) after treatment
      differed significantly depending on the degree of satisfaction (p < 0.001). IPSS
      V after treatment did not improve in patients who were 'not satisfied' or
      'totally not satisfied' (p = 0.170, 0.240, respectively). All the individual IPSS
      items except urgency (p = 0.1436) varied significantly with the degree of
      satisfaction (p < 0.001). CONCLUSIONS: Treating symptomatic BPH with low-dose
      tamsulosin improved IPSS, but more than one-third of patients were dissatisfied
      with the treatment. The main reason for dissatisfaction was efficacy problems,
      and the degree of satisfaction was related to symptom duration, baseline IPSS,
      and prostate size, and also to IPSS-V. In patients with severe LUTS, the
      tamsulosin dose should be increased earlier.

PMID- 23163503
TI  - Symptoms in heart failure correlate poorly with objective haemodynamic
      parameters.
AB  - INTRODUCTION: Even though heart failure (HF) is a very common condition,
      surprisingly little is known regarding association between patient's symptoms and
      objective data. The purpose of this study was to evaluate for any correlations
      between haemodynamic, echocardiographic and laboratory data of presenting
      symptoms in HF patients. METHODS: This study is a retrospective analysis of the
      limited access dataset from the Evaluation Study of Congestive Heart Failure and
      Pulmonary Artery Catheterization Effectiveness (ESCAPE) trial provided by the
      National Heart, Lung and Blood Institute. Symptoms including dyspnoea,
      orthopnoea, fatigue and gastrointestinal (GI) discomfort were graded by their
      severity from minimal (0) to maximal (3) on admission, at discharge, at 3 months
      and at 6 months from the admission. Results of Minnesota Living with Heart
      Failure (MLHF) score and assigned New York Heart Association (NYHA) functional
      class were available at the same time points. RESULTS: A total of 433 patients
      with decompensated HF and decreased systolic function (ejection fraction < 30%)
      were included in this trial. Orthopnoea, dyspnoea and fatigue had weak
      correlation with invasive pulmonary artery systolic and diastolic pressure and
      negative correlation with serum creatinine, albumin, sodium, total bilirubin,
      haemoglobin and haematocrit; fatigue showed positive correlation to pulmonary
      artery pressures. Abdominal discomfort had no correlation to symptoms. There was
      no correlation of symptoms, NYHA class, or MLHF scores with age, gender, peak
      VO(2) on cardiopulmonary stress test, body mass index, either right or left
      ventricular systolic function, B-type natriuretic peptide, cardiac output or
      cardiac index, troponin level, velocity of tricuspid regurgitation and multiple
      other factors predicting morbidity and mortality in HF. CONCLUSION: Overall, the
      correlation between symptoms and objective parameters was weak. Because of low
      magnitude of relationship between symptoms to objective parameters, it was
      concluded that there are likely other factors determining the perception of
      symptoms in HF patients.

PMID- 23163504
TI  - Quality improvement framework for major amputation: are we getting it right?
AB  - INTRODUCTION: The quality improvement framework for major amputation was
      developed with the aim of improving outcomes and reducing the perioperartive
      mortality to less than 5% by 2015. The aim of the study was to assess our
      compliance with the framework guidelines and look for the reasons for non
      compliance. METHOD: All major amputations performed between 2008 and 2010 were
      included. The following data were collected: presence of infection +/- tissue
      loss, status of arterial supply, revascularisation attempts, time to surgery,
      type of amputation, morbidity and mortality. RESULTS: A total of 81 patients were
      included (42 BKAs, 39 AKAs). Ninety percentage had formal preoperative arterial
      investigations and 84% had an attempted revascularisation procedure. Patients who
      were transferred late from non-vascular units (n = 12) had a 30-day mortality of
      50% whereas patients who presented directly to our unit had a 30-day mortality of
      7.2%. The number of amputations has decreased over the last 3 years from 34 to 21
      per year, coinciding with the doubling of crural revascularisation procedures
      performed (from 60 to 120 per year). Ten patients underwent a revision from BKA
      to AKA because of an inadequate profunda femoris artery (PFA), whereas all those
      with a healed BKA stump either had a good PFA or a named crural vessel.
      CONCLUSION: The overall number of amputations is decreasing from year to year. By
      doubling our crural revascularisation procedures we are saving more limbs. Thirty
      day mortality is higher than expected, particularly in patients who present late.
      Expeditious referral may potentially improve the mortality rate among this group
      of patients.

PMID- 23163505
TI  - Endobronchial ultrasound guided transbronchial needle aspiration--a sensitive and
      cost effective method of sampling mediastinal lymph nodes.

PMID- 23163506
TI  - Has myoglobin any unique role in current medical practice?

PMID- 23163508
TI  - Diversity patterns of uncultured Haptophytes unravelled by pyrosequencing in
      Naples Bay.
AB  - Haptophytes are a key phylum of marine protists, including ~300 described
      morphospecies and 80 morphogenera. We used 454 pyrosequencing on large subunit
      ribosomal DNA (LSU rDNA) fragments to assess the diversity from size-fractioned
      plankton samples collected in the Bay of Naples. One group-specific primer set
      targeting the LSU rDNA D1/D2 region was designed to amplify Haptophyte sequences
      from nucleic acid extracts (total DNA or RNA) of two size fractions (0.8-3 or 3
      20 MUm) and two sampling depths [subsurface, at 1 m, or deep chlorophyll maximum
      (DCM) at 23 m]. 454 reads were identified using a database covering the entire
      Haptophyta diversity currently sequenced. Our data set revealed several hundreds
      of Haptophyte clusters. However, most of these clusters could not be linked to
      taxonomically known sequences: considering OTUs(97%) (clusters build at a
      sequence identity level of 97%) on our global data set, less than 1% of the reads
      clustered with sequences from cultures, and less than 12% clustered with
      reference sequences obtained previously from cloning and Sanger sequencing of
      environmental samples. Thus, we highlighted a large uncharacterized environmental
      genetic diversity, which clearly shows that currently cultivated species poorly
      reflect the actual diversity present in the natural environment. Haptophyte
      community appeared to be significantly structured according to the depth. The
      highest diversity and evenness were obtained in samples from the DCM, and samples
      from the large size fraction (3-20 MUm) taken at the DCM shared a lower
      proportion of common OTUs(97%) with the other samples. Reads from the species
      Chrysoculter romboideus were notably found at the DCM, while they could be
      detected at the subsurface. The highest proportion of totally unknown OTUs(97%)
      was collected at the DCM in the smallest size fraction (0.8-3 MUm). Overall, this
      study emphasized several technical and theoretical barriers inherent to the
      exploration of the large and largely unknown diversity of unicellular eukaryotes.

PMID- 23163509
TI  - Incorporation of thrombin cleavage peptide into a protein cage for constructing a
      protease-responsive multifunctional delivery nanoplatform.
AB  - Protein cages are spherical hollow supramolecules that are attractive nanoscale
      platforms for constructing cargo delivery vehicles. Using ferritin isolated from
      the hyperthermophilic archaeon  Pyrococcus furiosus  (Pf_Fn), we developed a
      multifunctional protein cage-based delivery nanoplatform that can hold cargo
      molecules securely, deliver them to the targeted sites, and release them to the
      targeted cells. The release is triggered by cleavage induced by the protease,
      thrombin. The thrombin cleavage peptide (GGLVPR/GSGAS) was inserted into the
      flexible loop region of Pf_Fn, which is located at a 4-fold axis of symmetry
      exposed on the surface of protein cages (Thr-Pf_Fn). Subsequently, the C-terminal
      glycine, which is situated in the interior cavity, was substituted with cysteine
      (G173C) to permit site-specific conjugation of cargo molecules. The introduced
      cysteine (G173C) was labeled with a fluorescent probe (F5M-Thr-Pf_Fn) for cell
      imaging and cargo release monitoring. The surface of F5M-Thr-Pf_Fn was further
      modified with biotins (F5M-Thr-Pf_Fn-NPB) as targeting ligands. The specific
      binding of dual functionalized F5M-Thr-Pf_Fn-NPB to the MDA MB 231 cell line,
      which overexpresses biotin-specific receptors on its surface, was confirmed by
      fluorescence microscopic analyses. The inserted thrombin cleavage peptides were
      effectively cleaved by thrombin, resulting in the release of the C-terminal helix
      in buffer and on the targeted cells without disruption of the cage architecture.
      Protein cage scaffolds that combine genetic and chemical modifications may serve
      as stimulus-responsive delivery nanoplatforms and provide opportunities for
      developing new types of theranostic nanoplatforms.

PMID- 23163510
TI  - Comments on 'vascular effects of dietary nitrate (as found in green leafy
      vegetables and beetroot) via the nitrate-nitrite-nitric oxide pathway'.

PMID- 23163512
TI  - An Arabidopsis reticulon and the atlastin homologue RHD3-like2 act together in
      shaping the tubular endoplasmic reticulum.
AB  - The endoplasmic reticulum (ER) is a network of membrane sheets and tubules
      connected via three-way junctions. A family of proteins, the reticulons, are
      responsible for shaping the tubular ER. Reticulons interact with other tubule
      forming proteins (Dp1 and Yop1p) and the GTPase atlastin. The Arabidopsis
      homologue of Dp1/Yop1p is HVA22. We show here that a seed-specific isoform of
      HVA22 labels the ER in tobacco (Nicotiana tabacum) cells but its overexpression
      does not alter ER morphology. The closest plant homologue of atlastin is RHD3. We
      show that RHD3-like 2 (RL2), the seed-specific isoform of RHD3, locates to the ER
      without affecting its shape or Golgi mobility. Expression of RL2-bearing
      mutations within its GTPase domain induces the formation of large ER strands,
      suggesting that a functional GTPase domain is important for the formation of
      three-way junctions. Coexpression of the reticulon RTNLB13 with RL2 resulted in a
      dramatic alteration of the ER network. This alteration did not depend on an
      active GTPase domain but required a functional reticulon, as no effect on ER
      morphology was seen when RL2 was coexpressed with a nonfunctional RTNLB13. RL2
      and its GTPase mutants coimmunoprecipitate with RTNLB13. These results indicate
      that RL2 and RTNLB13 act together in modulating ER morphology.

PMID- 23163513
TI  - RAFT synthesis of ABA triblock copolymers as ionic liquid-containing
      electroactive membranes.
AB  - 2-(Dimethylamino)ethyl acrylate (DMAEA) imparts versatile functionality to
      poly[Sty-b-(nBA-co-DMAEA)-b-Sty] ABA triblock copolymers. A controlled synthetic
      strategy minimized chain transfer reactions and enabled the preparation of high
      molecular-weight ABA triblock copolymers with relatively narrow PDIs between 1.39
      and 1.44 using reversible addition-fragmentation chain transfer (RAFT)
      polymerization. The presence of tertiary amine functionality and their
      zwitterionic derivatives in the central blocks of the triblock copolymers
      afforded tunable polarity toward ionic liquids. Gravimetric measurements
      determined the swelling capacity of the triblock copolymers for ionic liquids
      (IL) 1-ethyl-3-methylimidazolium trifluoromethanesulfonate (EMIm TfO) and 1-ethyl
      3-methylimidazolium ethylsulfate (EMIm ES). A correlation of differential
      scanning calorimetry (DSC), dynamic mechanical analysis (DMA), and small-angle X
      ray scattering (SAXS) results revealed the impact of ionic liquid incorporation
      on the thermal transitions, thermomechanical properties, and morphologies of the
      triblock copolymers. IL-containing membranes of DMAEA-derived triblock copolymers
      and EMIm TfO exhibited desirable rubbery plateau moduli of ~100 MPa and
      electromechanical actuation to a 4 V electrical stimulus. Maintaining the
      mechanical ductility of polymer matrices while increasing their ion-conductivity
      is paramount for future electroactive devices.

PMID- 23163514
TI  - Genotype-by-environment interactions for cuticular hydrocarbon expression in
      Drosophila simulans.
AB  - Genotype-by-environment interactions (G * Es) describe genetic variation for
      phenotypic plasticity. Recent interest in the role of these interactions in
      sexual selection has identified G * Es across a diverse range of species and
      sexual traits. Additionally, theoretical work predicts that G * Es in sexual
      traits could help to maintain genetic variation, but could also disrupt the
      reliability of these traits as signals of mate quality. However, empirical tests
      of these theoretical predictions are scarce. We reared iso-female lines of
      Drosophila simulans across two axes of environmental variation (diet and
      temperature) in a fully factorial design and tested for G * Es in the expression
      of cuticular hydrocarbons (CHCs), a multivariate sexual trait in this species. We
      find sex-specific environmental, genetic and G * E effects on CHC expression,
      with G * Es for diet in both male and female CHC profile and a G * E for
      temperature in females. We also find some evidence for ecological crossover in
      these G * Es, and by quantifying variance components, genetic correlations and
      heritabilities, we show the potential for these G * Es to help maintain genetic
      variation and cause sexual signal unreliability in D. simulans CHC profiles.

PMID- 23163515
TI  - Surface charge dependent nanoparticle disruption and deposition of lipid bilayer
      assemblies.
AB  - Electrostatic interaction plays a leading role in nanoparticle interactions with
      membrane architectures and can lead to effects such as nanoparticle binding and
      membrane disruption. In this work, the effects of nanoparticles (NPs) interacting
      with mixed lipid systems were investigated, indicating an ability to tune both NP
      binding to membranes and membrane disruption. Lipid membrane assemblies (LBAs)
      were created using a combination of charged, neutral, and gel-phase lipids.
      Depending on the lipid composition, nanostructured networks could be observed
      using in situ atomic force microscopy representing an asymmetrical distribution
      of lipids that rendered varying effects on NP interaction and membrane disruption
      that were domain-specific. LBA charge could be localized to fluidic domains that
      were selectively disrupted when interacting with negatively charged Au
      nanoparticles or quantum dots. Disruption was observed to be related to the
      charge density of the membrane, with a maximum amount of disruption occurring at
      ~40% positively charged lipid membrane concentration. Conversely, particle
      deposition was determined to begin at charged lipid concentrations greater than
      40% and increased with charge density. The results demonstrate that the
      modulation of NP and membrane charge distribution can play a pivitol role in
      determining NP-induced membrane disruption and NP surface assembly.

PMID- 23163511
TI  - Emerging human papillomavirus vaccines.
AB  - INTRODUCTION: Identification of human papillomavirus (HPV) as the etiologic
      factor of cervical, anogenital, and a subset of head and neck cancers has
      stimulated the development of preventive and therapeutic HPV vaccines to control
      HPV-associated malignancies. Excitement has been generated by the
      commercialization of two preventive L1-based vaccines, which use HPV virus-like
      particles (VLPs) to generate capsid-specific neutralizing antibodies. However,
      factors such as high cost and requirement for cold chain have prevented
      widespread implementation where they are needed most. AREAS COVERED: Next
      generation preventive HPV vaccine candidates have focused on cost-effective
      stable alternatives and generating broader protection via targeting multivalent
      L1 VLPs, L2 capsid protein, and chimeric L1/L2 VLPs. Therapeutic HPV vaccine
      candidates have focused on enhancing T cell-mediated killing of HPV-transformed
      tumor cells, which constitutively express HPV-encoded proteins, E6 and E7.
      Several therapeutic HPV vaccines are in clinical trials. EXPERT OPINION: Although
      progress is being made, cost remains an issue inhibiting the use of preventive
      HPV vaccines in countries that carry the majority of the cervical cancer burden.
      In addition, progression of therapeutic HPV vaccines through clinical trials may
      require combination strategies employing different therapeutic modalities. As
      research in the development of HPV vaccines continues, we may generate effective
      strategies to control HPV-associated malignancies.

PMID- 23163516
TI  - Pyometra in a six-month-old nulliparous golden hamster (Mesocricetus auratus)
      treated with aglepristone.

PMID- 23163517
TI  - Anti-H5N1 virus new diglyceride ester from the Red Sea grass Thallasodendron
      ciliatum.
AB  - Some Egyptian plants were screened against highly pathogenic avian influenza
      strain H5N1 using plaque inhibition assay in Madin-Darby canine kidney. The
      results indicated that the extracts of Red Sea grass Thallasodendron ciliatum
      possessed potent antiviral activity (100% inhibition at the concentration of 1
      MUg mL-1). The bioactivity-guided fractionations led to the isolation of a new
      diglyceride ester (1) along with asebotin (2) for the first time from the plant.
      The two isolates showed reduction of virus titre by 67.26% and 53.81% inhibition
      at concentration of 1 ng mL-1, respectively.

PMID- 23163518
TI  - DNA damage by genotoxic hydroxyhalofuranones: an in silico approach to MX.
AB  - MX (3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone), a disinfection
      byproduct present in chlorinated drinking water, is one of the most potent
      mutagens known. Whereas its genotoxic effects are well documented, the mechanism
      by which MX exerts such an intense biological effect is still unclear. To gain
      further insight into both the general reactivity of hydroxyhalofuranones, and
      especially as regards their genotoxicity, here we report an in silico study of
      the aqueous reactivity of MX and two less powerful analogues (MXY, in general):
      (3-chloro-4-(chloromethyl)-5-hydroxy-2(5H)-furanone -CMCF- and 3-chloro-4
      (methyl)-5-hydroxy-2(5H)-furanone -MCF-). The following aspects were
      investigated: (i) the acid dissociation and isomerization equilibria of MXY, i.e.
      the species distribution among the possible isomers; (ii) the one-electron
      reduction potential of MXY; (iii) the guanosine and adenosine alkylation
      mechanism by MXY, which leads to covalent-DNA adducts; and (iv) the redox
      properties of the adducts. No significant differences were observed between MCF,
      CMCF, and MX, with a single exception: the unimolecular carbon-chlorine cleavage
      of some MX-nucleotide adducts may afford highly oxidative intermediates, which
      could be able to remove an electron from contiguous nucleotides directly,
      especially guanosine. This reaction would provide a pathway for the hypothesized
      ability of some hydroxyhalofuranones to oxidize DNA.

PMID- 23163519
TI  - Association between heart rate variability and systemic endothelin-1
      concentration in normal-tension glaucoma.
AB  - PURPOSE: To investigate the association between heart rate variability (HRV) and
      the plasma level of endothelin-1 (ET-1) in normal-tension glaucoma (NTG).
      MATERIALS AND METHODS: Twenty-four patients with NTG were enrolled. Subjects with
      systemic diseases were excluded. All patients underwent a complete ophthalmic
      examination and were referred to the rheumatology department, where HRV
      assessment was performed. Patients were divided into two groups according to the
      standard deviation of normal-normal intervals (SDNN). The low heart rate
      variability (LHV) group consisted of patients with SDNN values in the bottom half
      of range of values, and the high heart rate variability (HHV) group consisted of
      those with SDNN values in the upper half of the range. Blood samples were assayed
      for ET-1 concentrations, which were compared between the LHV and HHV groups. The
      relationships between the ET-1 level and HRV parameters were analyzed. RESULTS:
      The LHV group showed significantly lower ET-1 levels compared with the HHV group
      (0.57 +/- 1.09 versus 2.21 +/- 3.56 pg/ml, respectively; p = 0.04). Among the HRV
      parameters, the SDNN and total power were significantly associated with the
      systemic level of ET-1 (rho = 0.729, p < 0.001; rho = 0.713, p < 0.001,
      respectively). CONCLUSIONS: After excluding patients with systemic diseases, the
      plasma ET-1 level was associated with HRV parameters in patients with NTG. These
      observations suggest that the relationship between autonomic dysfunction and
      autoregulation may play a role in the pathogenesis of NTG.

PMID- 23163520
TI  - Normal mode analysis of the spectral density of the Fenna-Matthews-Olson light
      harvesting protein: how the protein dissipates the excess energy of excitons.
AB  - We report a method for the structure-based calculation of the spectral density of
      the pigment-protein coupling in light-harvesting complexes that combines normal
      mode analysis with the charge density coupling (CDC) and transition charge from
      electrostatic potential (TrEsp) methods for the computation of site energies and
      excitonic couplings, respectively. The method is applied to the Fenna-Matthews
      Olson (FMO) protein in order to investigate the influence of the different parts
      of the spectral density as well as correlations among these contributions on the
      energy transfer dynamics and on the temperature-dependent decay of coherences.
      The fluctuations and correlations in excitonic couplings as well as the
      correlations between coupling and site energy fluctuations are found to be 1
      order of magnitude smaller in amplitude than the site energy fluctuations.
      Despite considerable amplitudes of that part of the spectral density which
      contains correlations in site energy fluctuations, the effect of these
      correlations on the exciton population dynamics and dephasing of coherences is
      negligible. The inhomogeneous charge distribution of the protein, which causes
      variations in local pigment-protein coupling constants of the normal modes, is
      responsible for this effect. It is seen thereby that the same building principle
      that is used by nature to create an excitation energy funnel in the FMO protein
      also allows for efficient dissipation of the excitons' excess energy.

PMID- 23163521
TI  - Toxicity of melamine, an adulterant in fish feeds: experimental assessment of its
      effects on tilapia.
AB  - Unscrupulous inclusion of melamine in fish feeds can be harmful to fish and may
      be hazardous to human health. An eight-week feeding trial examined the effects of
      melamine (inclusion levels; 5-30 g kg-1 feed) on the growth performance, feed
      efficiency, histopathological changes and melamine residues in sex-reversed red
      tilapia, Oreochromis niloticus (L.) * O.mossambicus (Peters). Fish which received
      melamine-containing feeds grew less, utilized feeds less efficiently and
      performed poorly, besides exhibiting defects such as fin erosion, anorexia,
      sluggish swimming behaviour, paling/darkening of skin and low survival. Melamine
      concentration in the fish reflected its inclusion level in the feeds, and the
      content was higher in the viscera than in the fish fillet or whole fish.
      Histopathological alterations were evident in the kidney, liver and gills of fish
      subjected to melamine treatment - the severity of lesions corresponded to its
      dosage. Enlargement of renal tubules was observed in the kidney of fish fed with
      >=10 g melamine kg-1 feed, although, crystals were not deposited. Fish subjected
      to melamine insult had more prominent lesions in liver than in kidney. Toxic
      effects on the gills manifested as epithelial hyperplasia of the primary and
      secondary lamellae. The anomalies were severe at higher intake levels of
      melamine.

PMID- 23163522
TI  - Esophageal leiomyosarcoma: clinical analysis and surgical treatment of 12 cases.
AB  - Leiomyosarcoma of the esophagus is a rare malignant tumor with slow growth and
      late metastasis. The aim of this study was to reassess the clinical
      characteristics and treatment modality in one of the largest series of esophageal
      leiomyosarcomas from a single institution. From February 1973 to December 2011,
      12 cases of esophageal leiomyosarcoma were identified. The principal symptoms
      included progressive dysphagia in 11 cases (91.7%), retrosternal/back pain in
      four (33.3%), weight loss in four (33.3%), upper gastrointestinal hemorrhage in
      two (16.7%), and emesis in two (16.7%). The average duration of symptoms was 10.6
      months. The location of the primary tumor was in the middle thoracic esophagus in
      five cases, and lower thoracic esophagus in seven cases. Six cases were
      classified as the polypoid type, five cases as the infiltrative type, and only
      one case as the intramural type. All 12 of the patients underwent
      esophagectomies, and radical resections were achieved in these patients. Based on
      the Kaplan-Meier Method, the 3-, 5-, and 10-year survival rates were 80.0%,
      58.3%, and 31.1%, respectively, with a median survival of 63 months. Five-year
      survival rates for patients with polypoid or intramural tumors (n = 7) was 83.3%,
      and for patients with infiltrative tumor (n = 5) it was 25.0%. One of the
      patients had tumor resected four times and survived for 161 months. In
      conclusion, patients presenting with esophageal leiomyosarcomas have an excellent
      prognosis, and radical resection may achieve acceptable results. 

PMID- 23163523
TI  - Degree of handedness, emotion, and the perceived duration of auditory stimuli.
AB  - Humans exhibit a remarkable ability to accurately judge time intervals, but this
      ability varies among individuals and across situations. Research suggests that
      arousal and attentional factors are consistently associated with subjective time
      distortions, and emotions such as anger, which can elicit arousal and attract
      attention, have frequently been studied in this context. Typically, viewing angry
      faces seems to consistently produce time overestimation relative to neutral
      faces, and the present study investigates the possibility that this effect
      extends to angry voices by means of a temporal bisection task. Additionally, this
      paper furthers previous findings that interhemispheric interaction as quantified
      by handedness strength (i.e., the degree to which one favours one hand over the
      other) is related to how individuals perceive future time points on an imagined
      time task, and explores the possibility that handedness strength differences may
      also manifest as differences in bisection task performance. Results showed that
      handedness strength was associated with differences in time perception in both
      objective (bisection) and subjective (imagined) contexts. Bisection task data
      further revealed that the angry stimulus was associated with decreased temporal
      sensitivity and a greater propensity to categorise stimuli as "short" as compared
      to the same stimulus spoken in a neutral voice, which contrasts with studies
      conducted using angry faces. Possible attentional explanations for these findings
      and suggestions for future research directions are discussed. 

PMID- 23163524
TI  - Ultrafast dynamics of multiple exciton harvesting in the CdSe-ZnO system:
      electron injection versus Auger recombination.
AB  - We study multiple electron transfer from a CdSe quantum dot (QD) to ZnO, which is
      a prerequisite for successful utilization of multiple exciton generation for
      photovoltaics. By using ultrafast time-resolved spectroscopy we observe
      competition between electron injection into ZnO and quenching of multiexcitons
      via Auger recombination. We show that fast electron injection dominates over
      biexcitonic Auger recombination and multiple electrons can be transferred into
      ZnO. A kinetic component with time constant of a few tens of picoseconds was
      identified as the competition between injection of the second electron from a
      doubly excited QD and a trion Auger recombination. Moreover, we demonstrate that
      the multiexciton harvesting efficiency changes significantly with QD size. Within
      a narrow QD diameter range from 2 to 4 nm, the efficiency of electron injection
      from a doubly excited QD can vary from 30% to 70% in our system.

PMID- 23163525
TI  - Solitary plasmacytoma: 10 years' experience at All India Institute of Medical
      Sciences, New Delhi.
AB  - Plasma cell dyscrasias account for 1% of all malignancies and 10% of
      hematological malignancies. About 5% of patients with a plasma cell dyscrasia
      present with either solitary bone plasmacytoma (SBP) or, less commonly, a soft
      tissue mass, extramedullary plasmacytoma (EMP) of monoclonal plasma cells. In
      this study we present the clinical features, management and outcome of 60
      patients with solitary plasmacytoma, who constituted 5.6% of 1129 patients with
      plasma cell dyscrasias treated over a 10-year period at All India Institute of
      Medical Sciences. Median age was 49 years. Fifty-two had SBP and eight had EMP.
      Forty-nine (82%) patients received radiotherapy with or without surgical excision
      or chemotherapy. Five-year event-free survival (EFS) and overall survival (OS)
      were 45.5% and 91%, respectively. Median EFS and OS were 38 and 122 months,
      respectively. Five-year survival rates in patients who developed multiple myeloma
      and those who did not were 81% and 100%, respectively. The median time of
      progression to myeloma was 21 months.

PMID- 23163526
TI  - Ocular findings in patients with autoimmune liver disease.
AB  - PURPOSE: This is a collaborative study from the ophthalmology and
      gastroenterology departments of a tertiary care hospital, designed to investigate
      the ocular features in patients with autoimmune liver disease (ALD). METHODS:
      Seventy-two eyes of 36 patients with ALD, and 40 eyes of 20 controls with normal
      ocular findings were evaluated. Schirmer test, tear film break-up time,
      pachymetry, macular thickness with optic coherence tomography, and optic nerve
      head analysis with the HRT III were performed in addition to complete
      ophthalmologic examination. RESULTS: Of the 36 patients, 31 were female (86.1%)
      and 5 were male (13.9%). The average age of patients was 47.7 +/- 13.3 years (21
      76 years). Autoimmune hepatitis in 22 patients (61.1%), primary biliary cirrhosis
      in 10 patients (27.8%), and primary sclerosing cholangitis in 4 patients (11.1%)
      were detected as etiologic causes. Cataract was seen more often in the study
      group. Tear film break-up time and Schirmer test results were significantly lower
      in the study group than in the controls. Other parameters were not different from
      control group. CONCLUSIONS: ALD showed a marked preponderance of females, with
      sex ratios of 6 females per male supportive to literature. The basal tear
      secretion and tear film stability are lower, and the dry eye symptoms are more
      common among the cases with ALD.

PMID- 23163527
TI  - Behavior of 3-isobutyl-2-hydroxypyrazine (IBHP), a key intermediate in 3-isobutyl
      2-methoxypyrazine (IBMP) metabolism, in ripening wine grapes.
AB  - 3-Isobutyl-2-hydroxypyrazine (IBHP) is thought to be a key intermediate in both
      the biosynthesis and degradation of the herbaceous smelling 3-isobutyl-2
      methoxypyrazine (IBMP), but its behavior during the growing season is not well
      understood. First, an improved method for IBHP quantification was developed. A
      deuterated IBHP standard was added to samples prior to isolation by mixed-mode
      cation exchange solid phase extraction. Extracts were silylated prior to
      quantification by GC-MS. A limit of detection of ca. 20 ng/L could be achieved
      for a 100 mL juice sample. This method was used to quantify IBHP during the 2010
      growing season in berries of two clones of Cabernet franc in the Finger Lakes
      region of New York and of Merlot grown in the California Central Valley. For all
      three sources, IBHP was detectable at the earliest sampling point, and its
      concentration per berry increased to a maximum around veraison, 208-477 pg/berry.
      On a per berry basis, IBHP peaked and began to decline 1-2 weeks after IBMP,
      indicating that previous studies that sampled preveraison fruit have missed the
      true maximum value of IBHP. The highest per berry concentration of IBHP observed
      was in the California Merlot. However, after veraison, IBHP declined more rapidly
      in the California Merlot than in the New York Cabernet franc, such that the
      Merlot had the lowest IBHP concentration at harvest. Thus, IBHP at harvest cannot
      be used as a proxy for IBMP at veraison as was previously suggested.

PMID- 23163528
TI  - Distinguishing between direct and indirect effects of predators in complex
      ecosystems.
AB  - 1. Global declines in biodiversity have stimulated much research into the
      consequences of species loss for ecosystems and the goods and services they
      provide. Species at higher trophic levels are at greater risk of human-induced
      extinction yet remarkably little is known about the effects of consumer species
      loss across multiple trophic levels in natural complex ecosystems. Previous
      studies have been criticized for lacking experimental realism and appropriate
      temporal scale, running for short periods that are not sufficient to detect many
      of the mechanisms operating in the field. 2. We manipulated the presence of two
      predator species and two groups of their prey (primary consumers) and measured
      their independent and interactive effects on primary producers in a natural
      marine benthic system. The presence of predators and their prey was manipulated
      in the field for 14 months to distinguish clearly the direct and indirect effects
      of predators on primary producers and to identify mechanisms driving responses.
      3. We found that the loss of either predator species had indirect negative
      effects on species diversity and total cover of primary producers. These
      cascading effects of predator species loss were mediated by the presence of
      intermediate consumers. Moreover, the presence of different intermediate
      consumers, irrespective of the presence or absence of their predators, determined
      primary producer assemblage structure. We identified direct negative effects of
      predators on their prey and several indirect effects of predators on primary
      producers but not all interactions could have been predicted based on trophic
      level. 4. Our findings demonstrate the importance of trophic cascade effects
      coupled with non-trophic interactions when predicting the effects of loss of
      predator species on primary producers and consequently for ecosystem functioning.
      There is a pressing need for improved understanding of the effects of loss of
      consumers, based on realistic scenarios of diversity loss, to test conceptual
      frameworks linking predator diversity to variation in ecosystem functioning and
      for the protection of biodiversity, ecosystem functioning and related services. 

PMID- 23163529
TI  - Subtle CD20 positivity in the bone marrow of a patient who has a mucosa
      associated lymphoid tissue lymphoma should not be regarded as evidence of
      involvement in the bone marrow.
AB  - AIMS:   Bone marrow (BM) biopsies of some mucosa-associated lymphoid tissue
      (MALT) lymphoma patients show scattered or small clusters of CD20+ cells without
      definite lesions (subtle CD20 positivity). The aim of this study was to evaluate
      the clinical significance of BM involvement and subtle CD20 positivity in 122
      patients diagnosed with MALT lymphoma. METHODS AND RESULTS:   Patients were
      divided into three categories: BM involvement [BM(+)], subtle CD20 positivity,
      and no BM involvement [BM(-)]. Eleven (9%) showed BM involvement, and 17 (14%)
      showed subtle CD20 positivity. BM(+) patients had significantly worse progression
      free survival (PFS) than BM(-) patients [hazard ratio (HR) 6.25, P = 0.01], but
      there was no significant difference between subtle CD20 positivity and BM(-)
      patients. Patients with >30 CD3+ cells among 100 nucleated cells in the areas
      with increased numbers of CD3+ cells had significantly worse PFS than those with
      <15 CD3+ cells (HR 5.49, P = 0.02). BM(+) patients with >30 CD3+ cells had worse
      PFS than those with <=30 CD3+ cells (P = 0.029), with an extent of BM(+)
      involvement of >10% positively correlating with >30 CD3+ cells (P = 0.015).
      CONCLUSIONS:   Patients with BM(+) MALT lymphoma showed significantly worse PFS
      than those with subtle CD20 positivity and BM(-) MALT lymphoma, but the PFS of
      patients with subtle CD20 positivity MALT lymphoma was not significantly
      different from that of those with BM(-) MALT lymphoma. Increased numbers of BM T
      cells in MALT lymphoma patients might be suggestive of a worse prognosis.

PMID- 23163530
TI  - Lead-resistant Providencia alcalifaciens strain 2EA bioprecipitates Pb+2 as lead
      phosphate.
AB  - A lead-resistant bacteria isolated from soil contaminated with car battery waste
      were identified as Providencia alcalifaciens based on biochemical
      characteristics, FAME profile and 16S rRNA sequencing and designated as strain
      2EA. It resists lead nitrate up to 0.0014 mol l(-1) by precipitating soluble lead
      as insoluble light brown solid. Scanning electron microscopy coupled with energy
      dispersive X-ray spectrometric analysis (SEM-EDX) and X-ray diffraction
      spectroscopy (XRD) revealed extracellular light brown precipitate as lead
      orthophosphate mineral, that is, Pb(9) (PO(4))(6) catalysed by phosphatase
      enzyme. This lead-resistant bacterial strain also demonstrated tolerance to high
      levels of cadmium and mercury along with multiple antibiotic resistance.
      Providencia alcalifaciens strain 2EA could be used for bioremediation of lead
      contaminated environmental sites, as it can efficiently precipitate lead as lead
      phosphate.

PMID- 23163531
TI  - Evaluating the ability of Bayesian clustering methods to detect hybridization and
      introgression using an empirical red wolf data set.
AB  - Bayesian clustering methods have emerged as a popular tool for assessing
      hybridization using genetic markers. Simulation studies have shown these methods
      perform well under certain conditions; however, these methods have not been
      evaluated using empirical data sets with individuals of known ancestry. We
      evaluated the performance of two clustering programs, baps and structure, with
      genetic data from a reintroduced red wolf (Canis rufus) population in North
      Carolina, USA. Red wolves hybridize with coyotes (C. latrans), and a single
      hybridization event resulted in introgression of coyote genes into the red wolf
      population. A detailed pedigree has been reconstructed for the wild red wolf
      population that includes individuals of 50-100% red wolf ancestry, providing an
      ideal case study for evaluating the ability of these methods to estimate
      admixture. Using 17 microsatellite loci, we tested the programs using different
      training set compositions and varying numbers of loci. structure was more likely
      than baps to detect an admixed genotype and correctly estimate an individual's
      true ancestry composition. However, structure was more likely to misclassify a
      pure individual as a hybrid. Both programs were outperformed by a maximum
      likelihood-based test designed specifically for this system, which never
      misclassified a hybrid (50-75% red wolf) as a red wolf or vice versa. Training
      set composition and the number of loci both had an impact on accuracy but their
      relative importance varied depending on the program. Our findings demonstrate the
      importance of evaluating methods used for detecting admixture in the context of
      endangered species management.

PMID- 23163532
TI  - Impact on modes of inheritance and relative risks of using extreme sampling when
      designing genetic association studies.
AB  - Using extreme phenotypes for association studies can improve statistical power .
      We study the impact of using samples with extremely high or low traits on the
      alternative model space, the genotype relative risks, and the genetic models in
      association studies. We prove the following results: when the risk allele causes
      high-trait values, the more extreme the high traits, the larger the genotype
      relative risks, which is not always true for using extreme low traits; we also
      prove that a genetic model theoretically changes with more extreme trait except
      for the recessive or dominant models. Practically, however, the impact of
      deviations from the true genetic model at a functional locus due to selective
      sampling is virtually negligible. The implications of our findings are discussed.
      Numerical values are reported for illustrations.

PMID- 23163533
TI  - Polymerization of silicate on hematite surfaces and its influence on arsenic
      sorption.
AB  - Iron oxides and oxyhydroxides are important sorbents for arsenic in soils,
      sediments, and water treatment systems, but their long-term potential for arsenic
      retention may be diminished by the formation of polymeric silicate on their
      surfaces. To study these interactions, we first investigated the sorption of
      silicate to colloidal hematite (alpha-Fe(2)O(3)) in short-term (48 h) and long
      term (210 days) batch experiments. The polymerization of silicate on the hematite
      surface was monitored by attenuated total reflectance Fourier transform infrared
      (ATR-FTIR) spectroscopy. The pH dependence of silicate sorption exhibited a
      maximum between pH 9.0 and 9.5. The condensation of silicate on hematite surfaces
      adsorbed from monomeric silicate solutions steadily continued over the 210 day
      period, whereby surface polymerization was slower at pH 3 than at pH 6. The
      effect of silicate surface polymerization on arsenate and arsenite sorption was
      studied by use of hematite pre-equilibrated with silicate for different time
      periods of up to 210 days. The competitive effect of silicate on arsenate and
      arsenite sorption increased with increasing silicate pre-equilibration time. Only
      under strongly acidic conditions (pH 3), where silicate sorption was weakest and
      surface polymerization was slowest, was arsenate and arsenite sorption not
      affected by the presence of silicate. We conclude that the long-term exposure to
      dissolved silicate can decrease the potential of natural iron (oxyhydr)oxides for
      adsorbing inorganic arsenic.

PMID- 23163535
TI  - AgAu bimetallic Janus nanoparticles and their electrocatalytic activity for
      oxygen reduction in alkaline media.
AB  - Bimetallic AgAu Janus nanoparticles were prepared by galvanic exchange reactions
      of 1-hexanethiolate-passivated silver (AgC6) nanoparticles with gold(I)
      mercaptopropanediol complex. The AgC6 nanoparticles were deposited onto a solid
      substrate surface by the Langmuir-Blodgett method such that the galvanic exchange
      reactions were limited to the top face of the nanoparticles that was in direct
      contact with the gold(I) complex solution. The resulting nanoparticles exhibited
      an asymmetrical distribution not only of the organic capping ligands on the
      nanoparticle surface but also of the metal elements in the nanoparticle cores, in
      contrast to the bulk-exchange counterparts where these distributions were
      homogeneous within the nanoparticles, as manifested in contact angle, UV-vis,
      XPS, and TEM measurements. More interestingly, despite a minimal loading of Au
      onto the Ag nanoparticles, the bimetallic AgAu nanoparticles exhibited enhanced
      electrocatalytic activity in oxygen reduction reactions, as compared to the
      monometal AgC6 nanoparticles. Additionally, the electrocatalytic performance of
      the Janus nanoparticles was markedly better than the bulk-exchange ones,
      suggesting that the segregated distribution of the polar ligands from the apolar
      ones might further facilitate charge transfer from Ag to Au in the nanoparticle
      cores, leading to additional improvement of the adsorption and reduction of
      oxygen.

PMID- 23163534
TI  - Antimicrobial susceptibility testing of Streptococcus pneumoniae and Haemophilus
      influenzae --internal quality control as a quality tool on a national level.
AB  - Knowledge of the quality and conformity of antimicrobial resistance data is
      important for comparing resistance rates regionally and over time. In this study,
      we have evaluated these features of the Finnish national susceptibility
      surveillance data for two respiratory tract pathogens, Streptococcus pneumoniae
      and Haemophilus influenzae. For this purpose internal quality control results for
      two isolates (S. pneumoniae ATCC 49619 and H. influenzae ATCC 49247) were
      analyzed from 21 clinical microbiology laboratories over a 3-year period. The
      results show that standardization of the susceptibility testing methods has
      proceeded well. The number of protocols used for susceptibility testing has
      declined (from seventeen methods to two with S. pneumoniae and from eleven to
      three with H. influenzae) and the reproducibility is good. Nevertheless, we
      noticed that a few laboratories test and report susceptibility results without
      defined break-points and even include antimicrobials with questionable
      therapeutic effect. Another non-compliance with the standard was a lack of a
      regular control system to verify the attainment of the intended quality of
      results in some laboratories. Interlaboratory analysis of quality control results
      is a good way to evaluate the quality and conformity of national resistance data.
      Finnish laboratories have produced very reproducible and accurate susceptibility
      results in the pre-EUCAST period, which ended in 2011.

PMID- 23163536
TI  - Effect of Robo4 on retinal endothelial permeability.
AB  - PURPOSE: To examine the role of Roundabout 4 (Robo4) in retinal endothelial
      permeability and analyze the structural events that lead to barrier disruption.
      MATERIALS AND METHODS: Small interfering RNA (siRNA) technology was used to
      knockdown Robo4 expression to study its effects on the permeability of human
      retinal vascular endothelial cells (HRVECs) in vitro. The endothelial cell
      permeability was detected by measuring the flux of rhodamine B isothiocyanate
      (RITC)-dextran across the HRVEC monolayers. The impact of Robo4 siRNA on the
      expression of tight junction (TJ) proteins and the activation of LIM-kinase
      (LIMK)/cofilin pathway were measured by western blotting. The change of actin
      cytoskeleton was detected using indirect immunofluorescence. RESULTS: Robo4 siRNA
      increased the permeability of HRVEC monolayers. The expression levels of TJ
      associated proteins occludin and zonula occludens (ZO)-1 were suppressed in Robo4
      depleted cells. In addition, there was rearrangement of F-actin in HRVECs. These
      processes were induced through increased activity in the LIMK/cofilin pathway
      which coincided with a disruption in the barrier properties of retinal
      endothelial monolayers. CONCLUSIONS: Knockdown of Robo4 expression in HRVECs
      induced endothelial hyperpermeability associated with the downregulation of ZO-1,
      occludin, and the rearrangement of F-actin and that LIM-kinase 1 (LIMK1)/cofilin
      signal transduction system may be involved in the modulating process.

PMID- 23163538
TI  - HIV voluntary counselling and testing among recently initiated and traditionally
      circumcised men in the Eastern Cape Province of South Africa.
AB  - HIV voluntary counselling and testing (VCT) is a cornerstone of the national
      strategic plan for HIV/AIDS treatment, care and support in South Africa. However,
      research shows that the utilisation of VCT services is disappointingly low,
      particular among males. This article focuses on the factors associated with the
      intention to test for HIV-infection among recently initiated and traditionally
      circumcised men in the rural areas of Eastern Cape Province, South Africa.
      Individual face-to-face interviews were conducted among 1656 sexually active men.
      Logistic regression analyses were used to explore the association between
      intention to test for HIV and psychosocial factors. Overall, 35.1% of the
      participants reported ever having tested for HIV. Intention to test for HIV was
      positively associated with perceived probability of getting an STI, positive
      attitudes towards gender-based violence, received general teachings about being a
      responsible man and highest grade passed. These findings provide specific
      information that can be used in the development of a focused cultural sensitive
      STI/HIV prevention programme aimed to increase VCT uptake among sexually active
      young men, which can be integrated into initiation and health education
      practices.

PMID- 23163539
TI  - High-performing mesoporous iron oxalate anodes for lithium-ion batteries.
AB  - Mesoporous iron oxalate (FeC(2)O(4)) with two distinct morphologies, i.e., cocoon
      and rod, has been synthesized via a simple, scalable chimie douce precipitation
      method. The solvent plays a key role in determining the morphology and
      microstructure of iron oxalate, which are studied by field-emission scanning
      electron microscopy and high-resolution transmission electron microscopy.
      Crystallographic characterization of the materials has been carried out by X-ray
      diffraction and confirmed phase-pure FeC(2)O(4).2H(2)O formation. The critical
      dehydration process of FeC(2)O(4).2H(2)O resulted in anhydrous FeC(2)O(4), and
      its thermal properties are studied by thermogravimetric analysis. The
      electrochemical properties of anhydrous FeC(2)O(4) in Li/FeC(2)O(4) cells are
      evaluated by cyclic voltammetry, galvanostatic charge-discharge cycling, and
      electrochemical impedance spectroscopy. The studies showed that the initial
      discharge capacities of anhydrous FeC(2)O(4) cocoons and rods are 1288 and 1326
      mA h g(-1), respectively, at 1C rate. Anhydrous FeC(2)O(4) cocoons exhibited
      stable capacity even at high C rates (11C). The electrochemical performance of
      anhydrous FeC(2)O(4) is found to be greatly influenced by the number of
      accessible reaction sites, morphology, and size effects.

PMID- 23163540
TI  - Calcium-43 NMR studies of polymorphic transition of calcite to aragonite.
AB  - Phase transformation between calcite and aragonite is an important issue in
      biomineralization. To shed more light on the mechanism of this process at the
      molecular level, we employ solid-state (43)Ca NMR to study the phase
      transformation from calcite to aragonite as regulated by magnesium ions, with
      (43)Ca enrichment at a level of 6%. Using the gas diffusion approach, the phase
      of Mg-calcite is formed initially and the system subsequently transforms to
      aragonite as the reaction time proceeds. Our (43)Ca solid-state NMR data support
      the dissolution-recrystallization mechanism for the calcite to aragonite
      transition. We find that the (43)Ca NMR parameters of Mg-calcite are very similar
      to those of pure calcite. Under the high-resolution condition provided by magic
      angle spinning at 4 kHz, we can monitor the variation of the (43)Ca NMR
      parameters of the aragonite signals for the samples obtained at different
      reaction times. Our data suggest that in the presence of a significant amount of
      Mg(2+) ions, aragonite is the most stable polymorph of calcium carbonate. The
      initial precipitated crystallites of aragonite have spine-like morphology, for
      which the (43)Ca spin-lattice relaxation data indicate that the ions in the
      lattice have considerable motional dynamics. As the crystallinity of aragonite
      improves further, the (43)Ca T(1) parameter of the aragonite phase changes
      considerably and becomes very similar to that obtained for pure aragonite. For
      the first time, the difference in crystal morphologies and crystallinity of the
      aragonite phase has been traced down to the subtle difference in the motional
      dynamics at the molecular level.

PMID- 23163541
TI  - Fifty years of ibuprofen: advancing pain and fever management.

PMID- 23163542
TI  - Ibuprofen blood plasma levels and onset of analgesia.
AB  - BACKGROUND:   Ibuprofen is widely available as an over-the-counter treatment for
      pain and fever. New formulations are now available, with varying pharmacokinetic
      profiles. However, few studies have been specifically designed to examine the
      relationship between ibuprofen plasma levels and onset of analgesia. This study
      aimed to determine a value, or range of values, for the blood plasma level of
      ibuprofen at which onset of analgesia could be expected. METHODS:   Placebo
      controlled clinical trials, investigating the efficacy and pharmacokinetics of
      ibuprofen 200 mg and 400 mg, were identified. A retrospective posthoc analysis
      was performed on data from trials that incorporated time to perceived pain relief
      as an endpoint and the incidence of confirmed/unconfirmed perceptible pain relief
      was assessed. Mean ibuprofen blood plasma levels were computed at various time
      points using data from pharmacokinetic trials. RESULTS:   Two trials were
      identified with sufficient data to analyse time to onset of analgesia (Current
      Controlled Trials ISRCTN73768226, ISRCTN86009231). For 400 mg ibuprofen, the
      incidence of confirmed perceptible pain relief was significantly greater vs.
      placebo at 20 min post dosing (both studies). For 200 mg ibuprofen, significance
      was reached at 20 min (one study). In the 17 trials, with data on plasma
      concentrations for patients receiving 400 mg ibuprofen, the weighted mean value
      at 20 min post dosing was 8.4 MUg/ml (95% confidence interval, 6.8-10.1).
      CONCLUSIONS:   RESULTS of this study provide useful information for the
      development of new ibuprofen formulations. Further prospective studies and
      studies using other endpoints to define efficacy and onset would be of interest.

PMID- 23163543
TI  - Ibuprofen: from invention to an OTC therapeutic mainstay.
AB  - The discovery of ibuprofen's anti-inflammatory activity by Dr (now Professor)
      Stewart Adams and colleagues (Boots Pure Chemical Company Ltd, Nottingham, UK) 50
      years ago represented a milestone in the development of anti-inflammatory
      analgesics. Subsequent clinical studies were the basis for ibuprofen being widely
      accepted for treating painful conditions at high anti-rheumatic doses (<= 2400
      mg/d), with lower doses (<= 1200 mg/d for <= 10 days) for mild-moderate acute
      pain (e.g. dental pain, headache, dysmenorrhoea, respiratory symptoms and acute
      injury). The early observations have since been verified in studies comparing
      ibuprofen with newer cyclo-oxygenase-2 selective inhibitors ('coxibs'),
      paracetamol and other non-steroidal anti-inflammatory drugs (NSAIDs). The use of
      the low-dose, non-prescription, over-the-counter (OTC) drug was based on
      marketing approval in 1983 (UK) and 1984 (USA); and it is now available in over
      80 countries. The relative safety of OTC ibuprofen has been supported by large
      scale controlled studies. It has the same low gastro-intestinal (GI) effects as
      paracetamol (acetaminophen) and fewer GI effects than aspirin. Ibuprofen is a
      racemate. Its physicochemical properties and the short plasma-elimination half
      life of the R(-) isomer, together with its limited ability to inhibit cyclo
      oxygenase-1 (COX-1) and thus prostaglandin (PG) synthesis, compared with that of
      S(+)-ibuprofen, are responsible for the relatively low GI toxicity. The R(-)
      isomer is then converted in the body to the S(+) isomer after absorption in the
      GI tract. Ex vivo inhibition of COX-1 (thromboxane A(2)) and COX-2 (PGE(2)) at
      the plasma concentrations of S(+)-ibuprofen corresponding to those found in the
      plasma following ingestion of 400 mg ibuprofen in dental and other inflammatory
      pain models provides evidence of the anti-inflammatory mechanism at OTC dosages.
      R(-)-ibuprofen has effects on leucocytes, suggesting that ibuprofen has anti
      leucocyte effects, which underlie its anti-inflammatory actions. Future
      developments include novel gastro-tolerant forms for 'at risk' patients, and uses
      in the prevention of neuro-inflammatory states and cancers.

PMID- 23163544
TI  - Efficacy of OTC analgesics.
AB  - For many 'over-the-counter' (OTC) analgesics, there is little information
      available about their relative efficacy. We have examined information available
      in a series of Cochrane reviews of single doses of analgesic drugs in acute pain
      and migraine for its relevance for analgesic products commonly available without
      prescription, at doses generally equivalent to two tablets. Pain following third
      molar extraction was used as a homogeneous acute pain model; with the outcome of
      at least 50% maximum pain relief over 6 h. For many OTC drugs, there was no
      information available. For some OTC drugs, there was at least some information
      available either for the marketed product itself, or from studies that used the
      same doses of drug or drugs. For acute pain, data from third molar extraction
      studies showed that several OTC products were highly efficacious, principally non
      steroidal anti-inflammatory drugs (ibuprofen, naproxen, diclofenac) and
      combination products based on ibuprofen; aspirin and paracetamol-based products
      were less efficacious. Fixed-dose combinations, especially those with ibuprofen,
      provided high levels of analgesia. For migraine headache, the outcome used was
      pain initially moderate or severe becoming no worse than mild pain (no pain, mild
      pain) at 2 h. Single-dose ibuprofen 400 mg was better than aspirin and
      paracetamol.

PMID- 23163545
TI  - Optimising the management of fever and pain in children.
AB  - Fever and pain in children, especially associated with infections, such as otitis
      media, are very common. In paediatric populations, ibuprofen and paracetamol
      (acetaminophen) are both commonly used over-the-counter medicines for the
      management of fever or mild-to-moderate pain associated with sore throat, otitis
      media, toothache, earache and headache. Widespread use of ibuprofen and
      paracetamol has shown that they are both effective and generally well tolerated
      in the reduction in paediatric fever and pain. However, ibuprofen has the
      advantage of less frequent dosing (every 6-8 h vs. every 4 h for paracetamol) and
      its longer duration of action makes it a suitable alternative to paracetamol. In
      comparative trials, ibuprofen has been shown to be at least as effective as
      paracetamol as an analgesic and more effective as an antipyretic. The safety
      profile of ibuprofen is comparable to that of paracetamol if both drugs are used
      appropriately with the correct dosing regimens. However, in the overdose
      situation, the toxicity of paracetamol is not only reached much earlier, but is
      also more severe and more difficult to manage as compared with an overdose of
      ibuprofen. There is clearly a need for advanced studies to investigate the safety
      of these medications in paediatric populations of different ages and especially
      during prolonged use. Finally, the recently reported association between
      frequency and severity of asthma and paracetamol use needs urgent additional
      investigations.

PMID- 23163546
TI  - Headache: insight, understanding, treatment and patient management.
AB  - Tension-type headache and migraine are the most frequent primary headaches.
      Diagnosis is based on the patient's history and a normal neurological
      examination. Most patients with these two headache entities treat headache
      episodes with over-the-counter analgesics or non-steroidal anti-inflammatory
      drugs (NSAIDs). There is good scientific evidence from randomised, placebo
      controlled trials indicating that aspirin, ibuprofen, ketoprofen, diclofenac and
      naproxen are effective in tension-type and migraine headache. Paracetamol seems
      to be less effective. In patients with migraine who do not respond to analgesics
      or NSAIDs, triptans should be prescribed. Frequent primary headaches should not
      be treated with frequent intake of analgesics or triptans. In these cases,
      preventive therapy needs to be implemented.

PMID- 23163547
TI  - Gastrointestinal safety of NSAIDs and over-the-counter analgesics.
AB  - Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used. It is well
      recognised that they may adversely cause damage throughout the gastrointestinal
      tract and aggravate pre-existing disease. Their side effects on the upper
      gastrointestinal tract can be assessed by various means; each study type has
      different clinical connotations. Short-term use (less than 14 days) demonstrates
      dose-dependent damage of prescribed NSAIDs; the damage is proportional to the
      acidity of the drugs and not seen with Cyclooxygenase-2 (COX-2) selective
      inhibitors that have a pKa over 7.0. There have not been any serious outcomes,
      such as bleeding or perforation in these studies, and Helicobacter pylori (HP)
      plays no role in this damage. Long-term (3 months or more) endoscopy studies in
      patients show ulcer rates from 15%-35% with the various NSAIDs, but serious
      outcomes are exceedingly rare. Epidemiological studies show an association
      between NSAID intake and serious events. Ibuprofen is consistently at the lower
      end of toxicity rankings, whereas ketorolac and azapropazone are the worst. The
      risk of bleeding is increased with advancing age, presence of HP, previous
      history of bleeding, anticoagulant use, etc. The mega-trials show that COX-2
      selective agents halve the bleeding episodes, but NSAID-induced gastric bleeding
      is very rare usually, less than 1 in 200 subjects taking them for a year. Seventy
      percent of patients develop NSAID-enteropathy, which is associated with
      intestinal blood and protein loss and rarely strictures. Over-the-counter (OTC)
      use of ibuprofen and diclofenac is associated with symptomatic gastrointestinal
      side effects comparable with placebo. Ibuprofen is shown to be remarkably well
      tolerated at OTC doses in a number of studies. There are recent studies to
      suggest that OTC NSAIDs should be taken on a fasting stomach, not with food as
      commonly advocated.

PMID- 23163548
TI  - Ibuprofen: a model medicine for self-care of common conditions.
AB  - The expansion and development of the self-care agenda across Europe and beyond
      has the potential to realise huge efficiencies for national health services. Self
      medication of common ailments is one of the themes being developed by community
      pharmacy in several European countries. In the UK, as part of this development,
      ibuprofen was one of the first Prescription Only Medicines switched to Pharmacy
      Only (P) status and, arguably, the most successful. Within 4 years of switching,
      ibuprofen had 25% of the over-the-counter analgesic market and was a main choice
      for community pharmacists when recommending treatment for mild-to-moderate pain
      and fever in both adults and children over 6 months (now permitted from 3
      months). However, self-care of minor conditions appears not to be developing in
      line with the objectives of the self-care agenda. The reliance on national health
      systems for these conditions is still a major and unnecessary burden on health
      service resources. Taking ibuprofen use as a marker of this, whereas initially it
      was widely used for the effective and well-tolerated treatment of minor
      conditions, pharmacists now appear to offer significant barriers to its wider
      use. One reason for this could be criticism of community pharmacists' competence
      when dealing with and treating common conditions. For example, in the UK in the
      early 1980s, pharmacists have contributed to a risk averse approach. Another is
      that certain restrictions that may have been justified in 1983 when ibuprofen was
      granted P status (e.g. caution in asthmatic patients and patients with history of
      severe gastrointestinal complaints), have acted as a barrier to wider treatment
      with ibuprofen. However, there is currently little evidence to support the
      continued maintenance of all these barriers. Regulators may need to revisit the
      Summary of Product Characteristics and community pharmacists to update their
      knowledge of ibuprofen, and possibly other switched medicines, where unjustified
      barriers to use exist if pharmacists are to contribute more successfully to the
      self-care agenda.

PMID- 23163549
TI  - A normal psychology of everyday pain.
AB  - Proposed is a psychology of pain that focusses on normal psychological reactions
      to pain. A normal psychology of pain seeks to explain what normal people (those
      who would not meet any criteria for any psychological disorder) do when faced
      with pain. Herein, we focus on everyday pain defined as pain that is clinically
      unimportant that arises from normal everyday activity. Pain functions to
      interrupt current concerns and promote problem solving typically in the form of
      escape, pain management, or request for assistance. A model of analgesic problem
      solving is described. Focussing on pain as an interruption leads us to think
      about the purpose of analgesics in repairing attention and returning function.
      New endpoints for analgesic performance are offered. Similarly, a focus on pain
      as a motivation for analgesia demands that we understand how people self-medicate
      its relative success, and what influences patterns of self-medication. Finally,
      the problem of pain in children and adolescents, including self-medication in
      youth, is discussed. Although there is limited small-scale research on young
      people and their knowledge about analgesics, very little is known about their
      beliefs, attitudes to analgesics and their self-medication behaviour. Adolescents
      in most societies are left largely unguided. There is little child-specific
      communication about how to manage pain. Most children rely on parental knowledge,
      although increasingly the internet is becoming a source of advice for young
      people learning about analgesics.

PMID- 23163550
TI  - Overview of tomato (Solanum lycopersicum) candidate pathogen recognition genes
      reveals important Solanum R locus dynamics.
AB  - To investigate the genome-wide spatial arrangement of R loci, a complete
      catalogue of tomato (Solanum lycopersicum) and potato (Solanum tuberosum)
      nucleotide-binding site (NBS) NBS, receptor-like protein (RLP) and receptor-like
      kinase (RLK) gene repertories was generated. Candidate pathogen recognition genes
      were characterized with respect to structural diversity, phylogenetic
      relationships and chromosomal distribution. NBS genes frequently occur in
      clusters of related gene copies that also include RLP or RLK genes. This scenario
      is compatible with the existence of selective pressures optimizing coordinated
      transcription. A number of duplication events associated with lineage-specific
      evolution were discovered. These findings suggest that different evolutionary
      mechanisms shaped pathogen recognition gene cluster architecture to expand and to
      modulate the defence repertoire. Analysis of pathogen recognition gene clusters
      associated with documented resistance function allowed the identification of
      adaptive divergence events and the reconstruction of the evolution history of
      these loci. Differences in candidate pathogen recognition gene number and
      organization were found between tomato and potato. Most candidate pathogen
      recognition gene orthologues were distributed at less than perfectly matching
      positions, suggesting an ongoing lineage-specific rearrangement. Indeed, a local
      expansion of Toll/Interleukin-1 receptor (TIR)-NBS-leucine-rich repeat (LRR)
      (TNL) genes in the potato genome was evident. Taken together, these findings have
      implications for improved understanding of the mechanisms of molecular adaptive
      selection at Solanum R loci.

PMID- 23163551
TI  - Activation of the Si-B interelement bond: mechanism, catalysis, and synthesis.

PMID- 23163552
TI  - Glycoengineering of host mimicking type-2 LacNAc polymers and Lewis X antigens on
      bacterial cell surfaces.
AB  - Bacterial carbohydrate structures play a central role in mediating a variety of
      host-pathogen interactions. Glycans can either elicit protective immune response
      or lead to escape of immune surveillance by mimicking host structures.
      Lipopolysaccharide (LPS), a major component on the surface of Gram-negative
      bacteria, is composed of a lipid A-core and the O-antigen polysaccharide.
      Pathogens like Neisseria meningitidis expose a lipooligosaccharide (LOS), which
      outermost glycans mimick mammalian epitopes to avoid immune recognition. Lewis X
      (Galbeta1-4(Fucalpha1-3)GlcNAc) antigens of Helicobacter pylori or of the
      helminth Schistosoma mansoni modulate the immune response by interacting with
      receptors on human dendritic cells. In a glycoengineering approach we generate
      human carbohydrate structures on the surface of recombinant Gram-negative
      bacteria, such as Escherichia coli and Salmonella enterica sv. Typhimurium that
      lack O-antigen. A ubiquitous building block in mammalian N-linked protein glycans
      is Galbeta1-4GlcNAc, referred to as a type-2 N-acetyllactosamine, LacNAc,
      sequence. Strains displaying polymeric LacNAc were generated by introducing a
      combination of glycosyltransferases that act on modified lipid A-cores, resulting
      in efficient expression of the carbohydrate epitope on bacterial cell surfaces.
      The poly-LacNAc scaffold was used as an acceptor for fucosylation leading to
      polymers of Lewis X antigens. We analysed the distribution of the carbohydrate
      epitopes by FACS, microscopy and ELISA and confirmed engineered LOS containing
      LacNAc and Lewis X repeats by MALDI-TOF and NMR analysis. Glycoengineered LOS
      induced pro-inflammatory response in murine dendritic cells. These bacterial
      strains can thus serve as tools to analyse the role of defined carbohydrate
      structures in different biological processes.

PMID- 23163553
TI  - A review on epilepsy in the horse and the potential of Ambulatory EEG as a
      diagnostic tool.
AB  - Epilepsy in the horse is diagnosed based on clinical signs, but diagnosing can be
      difficult if a grand mal is not present. The future prospects of the horse and
      potentially the safety of the owner depend on an accurate diagnosis. This review
      presents information on epilepsy and focuses on the diagnostic potential of
      (Ambulatory) electroencephalography ((A) EEG). An epileptic seizure is a brain
      disorder, which expresses itself as a recurrent episode of involuntary abnormal
      behaviour. The aetiology can originate from inside or outside the brain or is
      idiopathic. Besides those categories, seizures can be classified as generalised
      or partial. A typical generalised tonic-clonic seizure is characterised by the
      prodrome, the ictus and the post-ictal phase. EEG is the graphic recording of
      rhythmic bioelectric activity which originates predominantly from the cerebral
      cortex. In human medicine, the 10/20 international basis system for electrode
      placement is used. This makes comparison more reliable and consistent. The normal
      human brainwaves recorded are alpha, beta, theta and delta waves. In the horse,
      fewer descriptions of normal signals are available. In humans suffering from
      epilepsy, spikes, complexes, spike-and-wave discharges and rhythmical multi-spike
      activity are seen. In horses suffering from epilepsy, spikes, sharp waves and
      spike-and-wave discharges are seen. In humans, AEEG has numerous advantages above
      short-duration EEG in diagnosing epilepsy or intracranial pathology. In future,
      AEEG might be useful to record brain signals in awake horses expressing their
      behaviour under natural circumstances.

PMID- 23163554
TI  - Manipulatory training during early postnatal ontogenesis effects on forelimb
      preference in food-reaching tasks in albino rats.
AB  - The influence of early manipulatory skill training on forepaw preference in adult
      state of rats was investigated. One group of Wistar rats was trained at the age
      of 21-28 days of life, another one at the age of 30-37 days of life. Second test
      of both groups was performed at the age of 120-127 days of life. It was found
      that after training at the age of 21 days of life adult rats had less expressed
      predominance in forepaw use and showed ambidextrous tendencies while most rats
      trained at the age of 30 days of life were lateralised. It is possible to suppose
      the existence of sensitive formation periods for forepaw preference based on
      whole organism growth. 

PMID- 23163555
TI  - Transmission of lymphocystis disease virus to cultured gilthead seabream, Sparus
      aurata L., larvae.
AB  - The transmission of lymphocystis disease virus (LCDV) to gilthead seabream,
      Sparus aurata L., larvae was investigated using fertilized eggs from a farm with
      previous reports of lymphocystis disease. LCDV genome was detected by PCR
      hybridization in blood samples from 17.5% of the asymptomatic gilthead seabream
      broodstock analysed. Using the same methodology, eggs spawned from these animals
      were LCDV positive, as well as larvae hatched from them. The presence of
      infective viral particles was confirmed by cytopathic effects development on SAF
      1 cells. Whole-mount in situ hybridization (ISH) and immunohistochemistry (IHC)
      showed the presence of LCDV in the epidermis of larvae hatched from LCDV-positive
      eggs. When fertilized eggs were disinfected with iodine, no viral DNA was
      detected either in eggs (analysed by PCR-hybridization) or in larvae (PCR
      hybridization and ISH). These results suggest the vertical transmission of LCDV,
      the virus being transmitted on the egg surface. Larvae hatched from disinfected
      eggs remain LCDV negative during the endotrophic phase, as showed by PCR
      hybridization, ISH and IHC. After feeding on LCDV-positive rotifers, viral
      antigens were observed in the digestive tract, which suggests that viral entry
      could be achieved via the alimentary canal, and that rotifers can act as a vector
      in LCDV transmission to gilthead seabream larvae.

PMID- 23163556
TI  - Immunosuppressive and biologic therapy for ulcerative colitis.
AB  - INTRODUCTION: Recent insight into the pathogenesis of ulcerative colitis have led
      to the development of new treatment options. A better understanding of IBD
      pathophysiology has progressively led to a more frequent use of
      immunosuppressants and biologics. AREAS COVERED: The use of the conventional
      immunomodulators, such as azathioprine, 6-mercaptopurine, methotrexate,
      cyclosporine and tacrolimus, and anti-TNF-alpha agents, such as infliximab and
      adalimumab, in the treatment of ulcerative colitis are reviewed. Moreover, the
      ongoing studies evaluating the efficacy of emerging immunosuppressants in
      treating patients with ulcerative colitis are discussed. An effort is made to
      explore some critical areas in which early and more diffuse use of these agents
      may be advocated. EXPERT OPINION: Ulcerative colitis is a chronic condition
      mainly affecting young people in their more productive age, and determining high
      indirect costs to the patient and to society. Thus, there is a need for
      optimizing and renewing our traditional therapeutic approach to UC, and new
      therapies beyond conventional treatment options possibly aiming to change the
      poor clinical course of many patients with ulcerative colitis. Keeping in mind
      this potentially new therapeutic scenario, there are some critical areas in which
      early and more diffuse use of conventional and emerging new immunomodulators is
      advocated.

PMID- 23163557
TI  - Free-standing mechanical and photonic nanostructures in single-crystal diamond.
AB  - A variety of nanoscale photonic, mechanical, electronic, and optoelectronic
      devices require scalable thin film fabrication. Typically, the device layer is
      defined by thin film deposition on a substrate of a different material, and
      optical or electrical isolation is provided by the material properties of the
      substrate or by removal of the substrate. For a number of materials this planar
      approach is not feasible, and new fabrication techniques are required to realize
      complex nanoscale devices. Here, we report a three-dimensional fabrication
      technique based on anisotropic plasma etching at an oblique angle to the sample
      surface. As a proof of concept, this angled-etching methodology is used to
      fabricate free-standing nanoscale components in bulk single-crystal diamond,
      including nanobeam mechanical resonators, optical waveguides, and photonic
      crystal and microdisk cavities. Potential applications of the fabricated
      prototypes range from classical and quantum photonic devices to nanomechanical
      based sensors and actuators.

PMID- 23163558
TI  - Thermochemistry of alkali metal cation interactions with histidine: influence of
      the side chain.
AB  - The interactions of alkali metal cations (M(+) = Na(+), K(+), Rb(+), Cs(+)) with
      the amino acid histidine (His) are examined in detail. Experimentally, bond
      energies are determined using threshold collision-induced dissociation of the
      M(+)(His) complexes with xenon in a guided ion beam tandem mass spectrometer.
      Analyses of the energy dependent cross sections provide 0 K bond energies of 2.31
      +/- 0.11, 1.70 +/- 0.08, 1.42 +/- 0.06, and 1.22 +/- 0.06 eV for complexes of His
      with Na(+), K(+), Rb(+), and Cs(+), respectively. All bond dissociation energy
      (BDE) determinations include consideration of unimolecular decay rates, internal
      energy of reactant ions, and multiple ion-neutral collisions. These experimental
      results are compared to values obtained from quantum chemical calculations
      conducted previously at the MP2(full)/6-311+G(2d,2p), B3LYP/6-311+G(2d,2p), and
      B3P86/6-311+G(2d,2p) levels with geometries and zero point energies calculated at
      the B3LYP/6-311+G(d,p) level where Rb and Cs use the Hay-Wadt effective core
      potential and basis set augmented with additional polarization functions (HW*).
      Additional calculations using the def2-TZVPPD basis set with B3LYP geometries
      were conducted here at all three levels of theory. Either basis set yields
      similar results for Na(+)(His) and K(+)(His), which are in reasonable agreement
      with the experimental BDEs. For Rb(+)(His) and Cs(+)(His), the HW* basis set and
      ECP underestimate the experimental BDEs, whereas the def2-TZVPPD basis set yields
      results in good agreement. The effect of the imidazole side chain on the BDEs is
      examined by comparing the present results with previous thermochemistry for other
      amino acids. Both polarizability and the local dipole moment of the side chain
      are influential in the energetics.

PMID- 23163559
TI  - Carotid artery dissection due to elongated styloid process: a self-stabbing
      phenomenon.
AB  - Elongated styloid process (ESP) is an anatomical variant that has been described
      as the cause of Eagle syndrome. Until recently, the styloid process has not been
      appreciated as a significant contributor to carotid artery dissection (CAD),
      which is not part of Eagle syndrome. We present a case of a 41-year-old male who
      presented with acute right middle cerebral artery occlusion and was found to have
      ESP projecting to and abutting the lateral wall of a dissected right internal
      carotid artery (ICA). Forced sustained head turning with maximal muscle
      contraction was the initiating event driving the styloid process into the wall of
      the ICA in a manner that can be likened to being stabbed with a pointed object.
      Knowing the association between ESP, Eagle syndrome, and CAD shall lead to
      increased awareness and appropriate diagnosis and treatment. 

PMID- 23163560
TI  - Commentary: risk factors for gastrointestinal bleeding in NSAID users.

PMID- 23163563
TI  - Letter: pyogenic liver abscess is a red flag sign of hepatocellular carcinoma.

PMID- 23163564
TI  - Letter: statin use and the risk of oesophageal cancer.

PMID- 23163566
TI  - Controlled, low-coverage metal oxide activation of silicon for organic
      functionalization: unraveling the phosphonate bond.
AB  - Deposition of thin films and grafting of organic molecules on semiconductor
      surfaces, particularly oxide surfaces, are widely studied as means of passivation
      and functionalization for a variety of applications. However, organic
      functionalization of silicon oxide is challenging, as the currently used
      molecules (silanes and phosphonates) do not form layers that are stable in
      aqueous environments and present challenges during the grafting process. For
      instance, the chemical grafting of phosphonates requires high temperature (140 
      degrees C) to perform. Modification of SiO(2) surfaces with metal oxides is an
      attractive alternative since strong bonds can be established between metal oxides
      and relevant molecules (silanes, phosphonates). While such modification is
      possible using vapor-phase methods, such as atomic layer deposition and physical
      vapor-phase deposition, wet chemical processing is inexpensive and
      technologically very attractive. We describe here a simple wet chemical method to
      deposit an ultrathin layer of metal oxide/hydroxide groups. Further, using a
      model surface with exactly one-third monolayer OH groups on oxide-free Si
      surfaces, the precise adsorption geometry on single Al(OH)(3) groups is shown to
      be bidentate, and the distance between the Al and P atoms is determined to be the
      main influencing parameter for a thermodynamically stable formation of the Al-O-P
      bond.

PMID- 23163565
TI  - Larval density dependence in Anopheles gambiae s.s., the major African vector of
      malaria.
AB  - Anopheles gambiae sensu stricto is the most important vector of malaria in Africa
      although relatively little is known about the density-dependent processes
      determining its population size. Mosquito larval density was manipulated under
      semi-natural conditions using artificial larval breeding sites placed in the
      field in coastal Kenya; two experiments were conducted: one manipulating the
      density of a single cohort of larvae across a range of densities and the other
      employing fewer densities but with the treatments crossed with four treatments
      manipulating predator access. In the first experiment, larval survival,
      development rate and the size of the adult mosquito all decreased with larval
      density (controlling for block effects between 23% and 31% of the variance in the
      data could be explained by density). In the second experiment, the effects of
      predator manipulation were not significant, but again we observed strong density
      dependence in larval survival (explaining 30% of the variance). The results are
      compared with laboratory studies of A. gambiae larval competition and the few
      other studies conducted in the field, and the consequences for malaria control
      are discussed.

PMID- 23163567
TI  - Methodology to reduce formaldehyde exposure during laboratory fumigation.
AB  - Laboratory fumigations achieve disinfection and are performed following the non
      contained release of infectious agents. Gaseous formaldehyde remains the most
      commonly used fumigant but evidence relates formaldehyde exposure to the
      development of nasopharyngeal cancer. Laboratory personnel must be confident and
      competent in the procedure to protect themselves, others and the environment. The
      present study outlines methodology to reduce worker exposure to formaldehyde
      during essential fumigation training. A simulation fumigation protocol
      significantly shorter than a genuine fumigation was devised using aromatic
      cajuput oil to train staff in the fumigation technique without potentially
      harmful exposure to formaldehyde. Personnel reported increased confidence and
      compliance of the fumigation procedure after the simulation suggesting that this
      model protocol would be a valuable training tool for any individual that may be
      required to undertake genuine formaldehyde fumigations.

PMID- 23163568
TI  - Trends in transfusion burden among long-term survivors of childhood hematological
      malignancies.
AB  - The risk from cumulative erythrocyte transfusions is poorly understood in
      oncology populations. This analysis among long-term survivors explored variation
      in transfusional burden over progressive eras of treatment identifying those at
      risk for iron overload. Transfusion records of 982 survivors of hematological
      malignancies treated at St. Jude were reviewed. After exclusions, 881 (90%) were
      assessed for cumulative volume, weight-adjusted volume and transfusion number.
      Treatment intensity was assigned using the Intensity of Treatment Rating Scale
      version 3.0 (ITR-3). Hematopoietic stem cell transplant and acute myeloid
      leukemia survivors had greater transfusional burden than conventional therapy
      recipients and acute lymphoblastic leukemia survivors, respectively. Survivors of
      5-10 years were more likely than survivors of > 10 years to receive >= 10
      transfusions (odds ratio = 2.0, 95% confidence interval 1.5-2.8). Those with
      higher ITR-3 scores and more recent decades of treatment had a higher
      transfusional burden. Comprehensive transfusion histories are useful in
      identifying those at highest risk for iron overload.

PMID- 23163569
TI  - Single-nucleotide polymorphisms of two closely related microsporidian parasites
      suggest a clonal population expansion after the last glaciation.
AB  - The mode of reproduction of microsporidian parasites has remained puzzling since
      many decades. It is generally accepted that microsporidia are capable of sexual
      reproduction, and that some species have switched to obligate asexuality, but
      such process had never been supported with population genetic evidence. We
      examine the mode of reproduction of Hamiltosporidium tvaerminnensis and
      Hamiltosporidium magnivora, two closely related microsporidian parasites of the
      widespread freshwater crustacean Daphnia magna, based on a set of 129 single
      nucleotide polymorphisms distributed across 16 genes. We analyse 20 H.
      tvaerminnensis isolates from localities representative of the entire species'
      geographic distribution along the Skerry Island belt of the Baltic Sea. Five
      isolates of the sister species H. magnivora were used for comparison. We estimate
      the recombination rates in H. tvaerminnensis to be at least eight orders of
      magnitude lower than in H. magnivora and not significantly different from zero.
      This is corroborated by the higher divergence between H. tvaerminnensis alleles
      (including fixed heterozygosity), as compared to H. magnivora. Our study confirms
      that sexual recombination is present in microsporidia, that it can be lost, and
      that asexuals may become epidemic.

PMID- 23163570
TI  - Association of toll-like receptor 4 polymorphisms with type 2 diabetes mellitus.
AB  - Toll-like receptor 4 (TLR4) plays important roles in modulating innate immunity.
      Type 2 diabetes mellitus (T2DM) is a chronic and complex disease that is
      characterized by impaired insulin resistance and dysregulated immune response. In
      the current study, we investigated whether TLR4 polymorphisms were correlated
      with susceptibility to T2DM in the Chinese population. Four TLR4 polymorphisms (
      2431T/C, Asp299Gly, Thr399Il3, and +3725G/C) were genotyped in 936 T2DM patients
      and 978 healthy controls. Results showed that the prevalence of TLR4 +3725GC and
      CC genotypes was significantly decreased in T2DM cases than those in controls
      [odds ratio (OR) = 0.68, 95% confidence interval (CI) = 0.55-0.84, p = 0.0003,
      and OR=0.46, 95% CI = 0.32-0.67, p = 3.71 * 10(-5) , respectively). Also, the
      frequency of TLR4 +3725C allele was significantly lower in T2DM patients (p =
      2.50 * 10(-8) ). The -2431T/C did not reveal any significant differences between
      cases and controls. We did not detect Asp299Gly and Thr399Il3 polymorphisms in
      our study group. Stratification analysis of the clinical features in the patients
      demonstrated that frequency of +3725CC genotype was lower in patients older than
      50 years old (p = 0.047). In conclusion, these results indicate that TLR4
      +3725G/C polymorphism may be a novel protective factor against T2DM in the
      Chinese population.

PMID- 23163571
TI  - Cyclin D1 in invasive breast carcinoma: favourable prognostic significance in
      unselected patients and within subgroups with an aggressive phenotype.
AB  - AIMS:   To study the clinicopathological and prognostic value of cyclin D1
      overexpression in patients with breast carcinoma. METHODS AND RESULTS:  
      Immunohistochemistry was performed on paraffin-embedded tissue specimens from 290
      invasive breast carcinomas to detect the proteins cyclin D1, oestrogen receptor
      (ER), progesterone receptor (PR), p53, c-erbB2, and topoisomerase IIalpha
      (topoIIalpha). Cyclin D1 staining was quantified using a computerized image
      analysis method. Cyclin D1 overexpression characterized smaller, ER-positive and
      PR-positive tumours (P = 0.017, P < 0.0001, and P < 0.0001, respectively), of a
      lower histological and nuclear grade (P = 0.011 and P < 0.0001, respectively),
      and with reduced expression of topoIIalpha (P = 0.001) and p53 (P < 0.001).
      Cyclin D1 was found to have an independent favourable impact on the overall
      survival of both the unselected cohort of patients (P = 0.011) and of patients
      with ER-negative and lymph node-positive tumours (P = 0.034 and P = 0.015,
      respectively). In triple-negative tumours, cyclin D1 overexpression was found to
      have independent favourable impacts on both overall and relapse-free survival (P
      = 0.002 for both). CONCLUSIONS:   This is the first immunohistochemical study to
      dissociate the advantageous prognostic effect of cyclin D1 overexpression from
      its association with ER expression, and to provide evidence that cyclin D1
      overexpression may be a marker of prolonged survival in patient subgroups with
      aggressive phenotypes.

PMID- 23163572
TI  - Fundus autofluorescence imaging in punctate inner choroidopathy with blind spot
      enlargement.
AB  - PURPOSE: To present a case report in which fundus autofluorescence (FAF) helped
      to diagnose and monitor the clinical course of a patient diagnosed with punctate
      inner choroidopathy (PIC). METHODS: Retrospective chart review of patient data.
      RESULTS: FAF showed multiple hypoautofluorescent spots in the posterior pole.It
      also showed an area of hypoautofluorescence surrounded by a ring of
      hyperautofluorescence, which corresponded to a larger lesion seen clinically. As
      the disease became inactive, the number of hypoautofluorescent spots decreased.
      The rim of hyperautofluorescence surrounding the macular lesion became
      attenuated.Persistent hypofluorescent areas grew in size. CONCLUSIONS: FAF is a
      useful imaging modality to better visualize and delineate the extent of damaged
      retinal pigment epithelium (RPE) in PIC. FAF also helps the clinician to assess
      the resolution of the disease by the appearance of the RPE.

PMID- 23163573
TI  - Dual blockade of angiotensin-II and aldosterone suppresses the progression of a
      non-diabetic rat model of steatohepatitis.
AB  - AIM: Both angiotensin-II (AT-II) and aldosterone (Ald) play pivotal roles in the
      pathogenesis of diseases in several organs including the liver. We previously
      reported that suppression of AT-II and Ald with angiotensin-converting enzyme
      inhibitor (ACE-I) and selective Ald blocker (SAB), respectively, attenuated the
      rat liver fibrogenesis and hepatocarcinogenesis. The aim of our current study was
      to elucidate the combined effects of ACE-I and SAB in the progression of a non
      diabetic rat model of steatohepatitis, and the possible mechanisms involved.
      METHODS: In the choline-deficient L-amino acid-defined (CDAA) diet-induced model,
      the effects of ACE-I and SAB on liver fibrosis development and
      hepatocarcinogenesis were elucidated, especially in conjunction with
      neovascularization. RESULTS: Treatment with both ACE-I and SAB suppressed the
      development of liver fibrosis and glutathione-S-transferase placental form (GST
      P) positive pre-neoplastic lesions. The combined treatment with both agents
      exerted more inhibitory effects as compared with either a single agent along with
      suppression of the activated hepatic stellate cells (Ac-HSC) and
      neovascularization, both of which play important roles in these processes. Our in
      vitro study showed that AT-II type 1 receptor blocker (ARB) and SAB inhibited Ac
      HSC proliferation and in vitro angiogenesis along with suppression of the in vivo
      studies. CONCLUSION: Dual blockade of AT-II and Ald suppresses the progression of
      a non-diabetic rat model of steatohepatitis. Because both agents are widely and
      safely used in clinical practice, this combination therapy could be an effective
      new strategy against steatohepatitis in the future.

PMID- 23163575
TI  - Spherical porphyrin sensor array based on encoded colloidal crystal beads for VOC
      vapor detection.
AB  - A spherical porphyrin sensor array using colloidal crystal beads (CCBs) as the
      encoding microcarriers has been developed for VOC vapor detection. Six different
      porphyrins were coated onto the CCBs with distinctive encoded reflection peaks
      via physical adsorption and the sensor array was fabricated by placing the
      prepared porphyrin-modified CCBs together. The change in fluorescence color of
      the porphyrin-modified CCBs array serves as the detection signal for
      discriminating between different VOC vapors and the reflection peak of the CCBs
      serves as the encoding signal to distinguish between different sensors. It was
      demonstrated that the VOC vapors detection using the prepared sensor array showed
      excellent discrimination: not only could the compounds from the different
      chemical classes be easily differentiated (e.g., alcohol vs acids vs ketones) but
      similar compounds from the same chemical family (e.g., methanol vs ethanol) and
      the same compound with different concentration ((e.g., Sat. ethanol vs 60 ppm
      ethanol vs 10 ppm ethanol) could also be distinguished. The detection
      reproducibility and the humidity effect were also investigated. The present
      spherical sensor array, with its simple preparation, rapid response, high
      sensitivity, reproducibility, and humidity insensitivity, and especially with
      stable and high-throughput encoding, is promising for real applications in
      artificial olfactory systems.

PMID- 23163574
TI  - Cell instructive microporous scaffolds through interface engineering.
AB  - The design of novel biomaterials for regenerative medicine requires incorporation
      of well-defined physical and chemical properties that mimic the native
      extracellular matrix (ECM). Here, we report the synthesis and characterization of
      porous foams prepared by high internal phase emulsion (HIPE) templating using
      amphiphilic copolymers that act as surfactants during the HIPE process. We
      combine different copolymers exploiting oil-water interface confined phase
      separation to engineer the surface topology of foam pores with nanoscopic domains
      of cell inert and active chemistries mimicking native matrix. We further
      demonstrate how proteins and hMSCs adhere in a domain specific manner.

PMID- 23163576
TI  - Dielectric relaxation of guest molecules in a clathrate structure of syndiotactic
      polystyrene.
AB  - Structure and dynamics of semicrystalline polymer films composed of syndiotactic
      polystyrene (sPS) and 2-butanone were examined through X-ray diffraction,
      polarized FTIR, and dielectric relaxation measurements. The X-ray and FTIR
      measurements revealed its crystal structure to be delta-clathrate containing 2
      butanone molecules inside. The carbonyl group of 2-butanone in the crystal was
      found to orient preferentially parallel to the ac plane of the crystal through
      the polarized ATR FTIR measurements. Dielectric measurements were also conducted
      on these film samples to see only the relaxation dynamics of 2-butanone thanks to
      the high dielectric intensity of 2-butanone compared to sPS. Two relaxation modes
      denoted by slow and fast modes appeared. The former was assigned to the motion of
      2-butanone molecules entrapped in the cavities of the crystalline (delta-form)
      and the latter to those in the amorphous region. We focused on the slow mode in
      order to elucidate the specific dynamics of the guest molecule confined in the
      crystalline region. The relaxation time of the slow mode was about 4 orders of
      magnitude longer than that of liquid 2-butanone. This suggests that the dynamics
      of guest molecules is highly restricted due to the high barrier to conformational
      and/or orientational change of the guest molecule in the cavity of delta-crystal.
      Furthermore, the dielectric intensity Deltaepsilon of the slow mode was much
      smaller than the one calculated from that of bulk liquid 2-butanone and the guest
      concentration in the crystalline region (the intensity was only 10% of the
      estimated value from the bulk liquid data). This result also indicates that the
      free rotational motion of 2-butanone molecules is restricted inside the crystal.
      This will be consistently related to the weak uniplanar orientation of the
      carbonyl group of 2-butanone parallel to the ac plane revealed by the X-ray and
      polarized ATR FTIR measurements.

PMID- 23163577
TI  - Influence of chelating agents on biogenic uraninite reoxidation by Fe(III)
      (Hydr)oxides.
AB  - Microbially mediated reduction of soluble U(VI) to U(IV) with subsequent
      precipitation of uraninite, UO(2(S)), has been proposed as a method for limiting
      uranium (U) migration. However, microbially reduced UO(2) may be susceptible to
      reoxidation by environmental factors, with Fe(III) (hydr)oxides playing a
      significant role. Little is known about the role that organic compounds such as
      Fe(III) chelators play in the stability of reduced U. Here, we investigate the
      impact of citrate, DFB, EDTA, and NTA on biogenic UO(2) reoxidation with
      ferrihydrite, goethite, and hematite. Experiments were conducted in anaerobic
      batch systems in PIPES buffer (10 mM, pH 7) with bicarbonate for approximately 80
      days. Results showed EDTA accelerated UO(2) reoxidation the most at an initial
      rate of 9.5 MUM day(-1) with ferrihydrite, 8.6 MUM day(-1) with goethite, and 8.8
      MUM day(-1) with hematite. NTA accelerated UO(2) reoxidation with ferrihydrite at
      a rate of 4.8 MUM day(-1); rates were less with goethite and hematite (0.66 and
      0.71 MUM day(-1), respectively). Citrate increased UO(2) reoxidation with
      ferrihydrite at a rate of 1.8 MUM day(-1), but did not increase the extent of
      reaction with goethite or hematite, with no reoxidation in this case. In all
      cases, bicarbonate increased the rate and extent of UO(2) reoxidation with
      ferrihydrite in the presence and absence of chelators. The highest rate of UO(2)
      reoxidation occurred when the chelator promoted both UO(2) and Fe(III)
      (hydr)oxide dissolution as demonstrated with EDTA. When UO(2) dissolution did not
      occur, UO(2) reoxidation likely proceeded through an aqueous Fe(III) intermediate
      with lower reoxidation rates observed. Reaction modeling suggests that strong
      Fe(II) chelators promote reoxidation whereas strong Fe(III) chelators impede it.
      These results indicate that chelators found in U contaminated sites may play a
      significant role in mobilizing U, potentially affecting bioremediation efforts.

PMID- 23163578
TI  - Serum procalcitonin is a valuable diagnostic marker in acute exacerbation of
      interstitial pneumonia.
AB  - BACKGROUND AND OBJECTIVE: Acute exacerbation (AE) of interstitial pneumonia (IP)
      is defined as a life-threatening deterioration of IP without identifiable cause.
      We evaluated the diagnostic and prognostic role of serum procalcitonin (PCT) in
      AE-IP. METHODS: Twenty consecutive patients admitted for AE-IP between May 2010
      and April 2012 were evaluated. Controls consisted of 13 consecutively admitted
      patients with acute respiratory distress syndrome (ARDS) due to bacterial
      pneumonia (BP) and 24 with bacterial pneumonia with stable IP ('BP with IP').
      Serum PCT was measured at baseline, at days 2, 4 and 8 in patients with AE-IP,
      and at baseline in controls. RESULTS: Serum PCT levels in AE-IP were
      significantly lower than in BP-ARDS (mean +/- standard deviation, 0.62 +/- 1.30
      vs 30.14 +/- 22.76 ng/mL; P < 0.0001) or 'BP with IP' (mean +/- standard
      deviation, 0.62 +/- 1.30 vs 8.31 +/- 14.83 ng/mL; P < 0.05). Thus, serum PCT
      discriminated well between AE-IP and BP-ARDS, or 'BP with IP' (area under the
      curve 0.99 and 0.85, respectively). However, there were no significant
      differences in serum PCT between 30-day survivors or non-survivors. Serum PCT
      tended to be reduced in both patient groups. CONCLUSIONS: Serum PCT is a useful
      marker for discriminating between AE-IP and BP. However, serum PCT is not useful
      as a prognostic marker for survival.

PMID- 23163579
TI  - Phenolic antioxidant scavenging of myosin radicals generated by hypervalent
      myoglobin.
AB  - The scavenging activity of extracts of green tea (GTE), white grape (WGE), and
      rosemary (RE), all plant material with high phenolic content, and of the phenolic
      compounds 4-methylcatechol (4-MC), (+)-catechin, and carnosic acid toward long
      lived myosin radicals generated by reaction with H2O2-activated myoglobin at room
      temperature (pH 7.5, I=1.0) was investigated by freeze-quench ESR spectroscopy.
      Myosin radicals were generated by incubating 16 MUM myosin, 800 MUM metmyoglobin,
      and 800 MUM H2O2 for 10 min, and the phenolic extracts were subsequently added
      (1% (w/w) phenolic compounds relative to myosin). GTE was able to scavenge myosin
      radicals and reduce the radical intensity by 65%. Furthermore, a low
      concentration of 4-MC (33 MUM) was found to increase the radical concentration
      when added to the myosin radicals, whereas a higher concentration of 4-MC and
      catechin (330 MUM) was found to scavenge myosin radicals and reduce the overall
      radical concentration by ~65%.

PMID- 23163580
TI  - Miniature enzyme-based electrodes for detection of hydrogen peroxide release from
      alcohol-injured hepatocytes.
AB  - Alcohol insult to the liver sets off a complex sequence of inflammatory and
      fibrogenic responses. There is increasing evidence that hepatocytes play a key
      role in triggering these responses by producing inflammatory signals such as
      cytokines and reactive oxygen species (ROS). In the present study, we employed a
      cell culture/biosensor platform consisting of electrode arrays integrated with
      microfluidics to monitor extracellular H(2)O(2), one of the major ROS types,
      produced by primary rat hepatocytes during alcohol injury. The biosensor
      consisted of hydrogel microstructures with entrapped horseradish peroxidase (HRP)
      immobilized on an array of miniature gold electrodes. These arrays of sensing
      electrodes were integrated into microfluidic devices and modified with collagen
      (I) to promote hepatocyte adhesion. Once seeded into the microfluidic devices,
      hepatocytes were exposed to 100 mM ethanol and the signal at the working
      electrode was monitored by cyclic voltammetry (CV) over the course of 4 h. The CV
      experiments revealed that hepatocytes secreted up to 1.16 MUM H(2)O(2) after 3 h
      of stimulation. Importantly, when hepatocytes were incubated with antioxidants or
      alcohol dehydrogenase inhibitor prior to alcohol exposure, the H(2)O(2) signal
      was decreased by ~5-fold. These experiments further confirmed that the biosensor
      was indeed monitoring oxidative stress generated by the hepatocytes and also
      pointed to one future use of this technology for screening hepatoprotective
      effects of antioxidants.

PMID- 23163581
TI  - Neurobehavioral problems following low-level exposure to organophosphate
      pesticides: a systematic and meta-analytic review.
AB  - Meta-analysis was carried out to determine the neurotoxic effects of long-term
      exposure to low levels of organophosphates (OPs) in occupational settings.
      Concern about the effects of OPs on human health has been growing as they are
      increasingly used throughout the world for a variety of agricultural, industrial
      and domestic purposes. The neurotoxic effects of acute poisoning are well
      established but the possibility that low-level exposure causes ill health is
      controversial. It is important to get a clear answer to this question as more
      individuals are at risk of low-level exposure than acute poisoning. Although a
      number of reviews on this topic have been published in the past, authors have
      come to conflicting conclusions. To date, none of these reviews have attempted
      quantitative evaluation of study findings using meta-analysis. This paper reviews
      the available evidence concerning the neurotoxicity of low-level occupational
      exposure to OPs and goes on to report the results of a meta-analysis of 14
      studies which fulfilled criteria for this type of statistical analysis (means and
      standard deviations of dependant variables reported). Data were assimilated from
      more than 1600 participants. The majority of well designed studies found a
      significant association between low-level exposure to OPs and impaired
      neurobehavioral function which is consistent, small to moderate in magnitude and
      concerned primarily with cognitive functions such as psychomotor speed, executive
      function, visuospatial ability, working and visual memory. Unresolved issues in
      the literature which should become the focus of further studies are highlighted
      and discussed.

PMID- 23163582
TI  - Involvement of three meningococcal surface-exposed proteins, the heparin-binding
      protein NhbA, the alpha-peptide of IgA protease and the autotransporter protease
      NalP, in initiation of biofilm formation.
AB  - Neisseria meningitidis is a common and usually harmless inhabitant of the mucosa
      of the human nasopharynx, which, in rare cases, can cross the epithelial barrier
      and cause meningitis and sepsis. Biofilm formation favours the colonization of
      the host and the subsequent carrier state. Two different strategies of biofilm
      formation, either dependent or independent on extracellular DNA (eDNA), have been
      described for meningococcal strains. Here, we demonstrate that the
      autotransporter protease NalP, the expression of which is phase variable, affects
      eDNA-dependent biofilm formation in N. meningitidis. The effect of NalP was found
      in biofilm formation under static and flow conditions and was dependent on its
      protease activity. Cleavage of the heparin-binding antigen NhbA and the alpha
      peptide of IgA protease, resulting in the release of positively charged
      polypeptides from the cell surface, was responsible for the reduction in biofilm
      formation when NalP is expressed. Both NhbA and the alpha-peptide of IgA protease
      were shown to bind DNA. We conclude that NhbA and the alpha-peptide of IgA
      protease are implicated in biofilm formation by binding eDNA and that NalP is an
      important regulator of this process through the proteolysis of these surface
      exposed proteins.

PMID- 23163583
TI  - Risk of postpartum uterine synechiae following uterine compression suturing
      during postpartum haemorrhage.
AB  - BACKGROUND: Uterine compression suturing is considered a successful, safe,
      inexpensive and simple method for the conservative treatment of atonic postpartum
      haemorrhage (PPH). However, insufficient data are available about the potential
      risk of subsequent intrauterine synechiae (IUS). AIM: To determine the risk of
      postpartum uterine synechiae in women who received isolated uterine compression
      suturing for the management of major uncontrolled PPH. MATERIALS & METHODS: All
      women with major PPH from May 2005 to June 2011 were reviewed retrospectively.
      Diagnostic hysteroscopy was performed to assess the uterine cavity in the 27
      women who successfully underwent isolated uterine compression suturing for major
      atonic PPH and fulfilled the study inclusion and exclusion criteria. RESULTS:
      Among the 27 women who underwent isolated uterine compression suturing, 5 (18.5%)
      were found to have IUS on hysteroscopic examination. The mode of delivery for all
      women who developed IUS was caesarean section. Among these five women, three had
      mild IUS, one had moderate IUS and one had severe IUS. All adhesions were later
      successfully resected by hysteroscopy, except for one case with dense IUS.
      CONCLUSIONS: Uterine compression suturing was found to be associated with a risk
      of postpartum uterine synechiae formation, which may subsequently affect future
      fertility.

PMID- 23163584
TI  - Ligand binding induces a conformational change in epidermal growth factor
      receptor dimers.
AB  - The activation of the epidermal growth factor receptor (EGFR) kinase requires
      ligand binding to the extracellular domain (ECD). Previous reports demonstrate
      that the EGFR-ECD can be crystallized in two conformations - a tethered monomer
      or, in the presence of ligand, an untethered back-to-back dimer. We use Biosensor
      analysis to demonstrate that even in the monomeric state different C-terminal
      extensions of both truncated (EGFR(1-501))-ECD and full-length EGFR(1-621)-ECD
      can change the conformation of the ligand-binding site. The binding of a
      monoclonal antibody mAb806, which recognizes the dimer interface, to the
      truncated EGFR(1-501)-Fc fusion protein is reduced in the presence of ligand,
      consistent with a change in conformation. On the cell surface, the presence of
      erythroblastosis B2 (erbB2) increases the binding of mAb806 to the EGFR. The
      conformation of the erbB2: EGFR heterodimer interface changes when the cells are
      treated with epidermal growth factor (EGF). We propose that ligand induces kinase
      inactive, pre-formed EGFR dimers and heterodimers to change conformation leading
      to kinase-active tetramers, where kinase activation occurs via an asymmetric
      interaction between EGFR dimers.

PMID- 23163585
TI  - CpG inclusion in feed reduces sea lice, Lepeophtheirus salmonis, numbers
      following re-infection.
AB  - Lepeophtheirus salmonis infections in Atlantic salmon, Salmo salar, have been
      characterized by little to no hyperplastic response and a biphasic immune
      response that results in chronic inflammation with tissue repair as the infection
      progresses. We hypothesized that CpG administration with prior lice exposure
      would enhance epithelial inflammatory mechanisms and boost the Atlantic salmon
      immune response to L. salmonis, leading to greater protection against infection.
      We administered multiple exposures of L. salmonis to two groups of Atlantic
      salmon and compared responses against first-time exposed Atlantic salmon.
      Following re-exposure, CpG fed fish exhibited increased skin expression of
      interleukin (IL)-1beta and IL-12 beta compared to control previously exposed
      (CPE) and control first-time exposed (CFE) animals, respectively. This
      inflammatory enhancement occurred with significantly lower expression of matrix
      metalloproteinase-9 (MMP 9), both systemically (spleen) and locally (skin).
      Reduced MMP 9 expression was a hallmark of the re-infected fish (occurred in both
      tissues at both times). When significant differences were present in the skin or
      spleen, the two re-exposed groups showed greater similarity than with the first
      exposure group. Lice numbers on CpG fed fish were significantly lower than CFE
      fish at 7 days post-re-infection (dpri), and although they were not significantly
      different at 17 dpri, the trend of lower lice levels remained. CpG fed fish also
      showed nearly twofold greater protection than CPE when compared to the CFE group
      (48.5% vs. 27.0% reductions at 7 dpri and 27.2% vs. 13.1% reductions at 17 dpri,
      respectively). The enhanced protection of CpG oligodeoxynucleotide administration
      to previous exposure was consistent across all body surfaces and suggests that
      CpG can not only enhance innate responses to L. salmonis in Atlantic salmon, but
      also further stimulate adaptive responses.

PMID- 23163586
TI  - Tracking the eyes to see what children remember.
AB  - Relational memory is a canonical form of episodic memory known to rely on the
      hippocampus. Several lines of evidence suggest that relational memory has a
      developmental trajectory in which it is fragile, inflexible, and error-prone
      until around 6 years of age, which seems to mirror maturational changes in the
      morphology of the hippocampus. However, recent findings from Richmond and Nelson
      (2009) challenge this idea as they provide evidence suggestive of adult-like
      relational memory in 9-month-old infants. In this study the authors measured the
      eye movements of infants and showed that they preferentially gazed at correct, as
      opposed to incorrect, face-scene pairings at test. The goal of the present study
      was to evaluate the development of relational memory by assessing 4-year-olds
      using Richmond and Nelson's task and stimuli, but gathering two dependent
      measures of relational memory: overt response as well as eye movements. The
      results show that, overall, preferential looking at correct face-scene pairings
      was at chance; however, preferential looking was observed when the correct face
      scene pair was later explicitly identified. Thus, while eye movements do index
      explicit memory in 4-year-olds, behavioural data are necessary to obtain a full
      picture of the development of relational memory in childhood.

PMID- 23163587
TI  - Analogue of the quantum Hanle effect and polarization conversion in non-Hermitian
      plasmonic metamaterials.
AB  - The Hanle effect, one of the first manifestations of quantum theory introducing
      the concept of coherent superposition between pure states, plays a key role in
      numerous aspects of science varying from applicative spectroscopy to fundamental
      astrophysical investigations. Optical analogues of quantum effects help to
      achieve deeper understanding of quantum phenomena and, in turn, to develop cross
      disciplinary approaches to realizations of new applications in photonics. Here we
      show that metallic nanostructures can be designed to exhibit a plasmonic analogue
      of the quantum Hanle effect and the associated polarization rotation. In the
      original Hanle effect, time-reversal symmetry is broken by a static magnetic
      field. We achieve this by introducing dissipative level crossing of localized
      surface plasmons due to nonuniform losses, designed using a non-Hermitian
      formulation of quantum mechanics. Such artificial plasmonic "atoms" have been
      shown to exhibit strong circular birefringence and circular dichroism which
      depends on the value of loss or gain in the metal-dielectric nanostructure.

PMID- 23163588
TI  - Effect of ion energies on the surface interactions of NO formed in nitrogen oxide
      plasma systems.
AB  - The contributions of various gas-phase species in surface reactions are of
      significant value to assess and improve catalytic substrates for abatement of
      vehicular emissions. The impact of ions on surface scatter of NO radicals is
      investigated with an aim toward improving and tailoring surfaces for the
      reduction or removal of nitrogen oxide (N(x)O(y)) species via inductively coupled
      plasmas (ICPs). Nascent ions are monitored via mass spectrometry and energy
      analysis for a variety of N(x)O(y) precursor gases. The total average ion energy
      (<E(i)>(total)) determined for all ions within each respective plasma system
      shows a strong positive correlation with applied rf power and a negative
      correlation with system pressure. The imaging of radicals interacting with
      surfaces (IRIS) technique was used to determine the role ions play in the surface
      scatter of NO radicals. The net effect of ions on substrate processing is largely
      dependent upon <E(i)>(total). Scatter coefficients (S), determined for ion
      limited and ion-rich plasma systems were used to correlate <E(i)>(total) and
      scatter. The resultant effect is that ions play a substantial role in scatter of
      NO only when <E(i)>(total) > ~50 eV. The majority of systems studied contained
      ions below this energy threshold, suggesting knowledge of ion energies is
      integral to appropriately controlling the chemistry occurring between the gas
      phase and surface.

PMID- 23163589
TI  - Emerging immunosuppressive drugs in myelodysplastic syndromes.
AB  - INTRODUCTION: Myelodysplastic syndromes (MDS) are characterized by dysplastic
      morphologic features and ineffective hematopoiesis. Pathophysiological
      characteristics change over time making therapeutic development a major
      challenge. In early MDS, cytopenias arise or are exacerbated by humoral and
      cellular immune-mediators that suppress hematopoietic progenitor survival and
      alter the bone marrow microenvironment. AREAS COVERED: In this review, current
      immunosuppressive regimens are described. To identify new therapies that may
      enhance immunosuppressive therapy (IST) response and identify pharmacodynamic
      biomarkers for patient selection, the inflammasome, cytokines, metabolic pathways
      and signaling events are described. EXPERT OPINION: Agents with the potential to
      induce early, durable hematologic remissions are needed and many new
      immunosuppressive agents are available for investigation. An immune-mediated
      mechanism is likely to contribute to MDS early after diagnosis. New approaches
      that interfere with inflammatory pathways in the bone marrow microenvironment may
      move closer toward sustained disease control in MDS.

PMID- 23163590
TI  - Variability in diagnosing Creutzfeldt-Jakob disease using standard and proposed
      diagnostic criteria.
AB  - INTRODUCTION: Creutzfeldt-Jakob disease (CJD) is a rapidly progressive dementia
      with a median survival of 2-14 months. The diagnosis can only be made accurately
      by biopsy/autopsy. However, this is not always feasible or desirable. Thus,
      diagnostic criteria have been proposed by UCSF, European MRI-CJD Consortium, and
      WHO. We will compare these criteria. PATIENTS AND METHODS: Retrospective study of
      31 patients (average age of 69.2 years) between 2003 to 2010 by ICD9 codes 046.1,
      046.11, and 046.19. RESULTS: All patients presented with rapidly progressive
      dementia (mean duration of 4.25 months). Pyramidal and extrapyramidal findings,
      myoclonus, cerebellar changes, akinetic mutism, and visual disturbances were
      observed in 6.5-48.4%. Five had periodic pattern on EEG. CSF biomarker 14-3-3 was
      positive in 11. Tau was positive in 6. Neuron specific enolase was positive in 9.
      By consensus (kappa = 0.62), MRI was "typical" of CJD in 23 with cortical
      ribboning (n = 16), basal ganglia hyperintensity (n = 15), or combination (n =
      8). By WHO criteria, which does not include neuroimaging, CJD was diagnosed in
      10, but 14 if any CSF biomarker was used (p = NS). The UCSF criteria, which does
      not include CSF biomarkers, diagnosed 18 cases, and the European MRI-CJD
      Consortium, which includes neuroimaging and CSF biomarkers but with less
      neurological signs, diagnosed 23 cases (p < 0.05 and p < 0.001, respectively).
      CJD-mimics included urosepsis, neurosarcoidosis, idiopathic left temporal lobe
      epilepsy, alcohol intoxication, central nervous system vasculitis, viral
      encephalitis, and non-Hodgkin's lymphoma. CONCLUSION: This study illustrates the
      variability in diagnosing CJD and emphasizes the diagnostic utility of
      neuroimaging. It also highlights false-positives that occur with neuroimaging.

PMID- 23163591
TI  - Synthesis of beta-cyclodextrin diazonium salts and electrochemical immobilization
      onto glassy carbon and gold surfaces.
AB  - This study shows that diazotized beta-cyclodextrin (beta-CD) can be produced,
      isolated, and immobilized onto glassy carbon and gold surfaces. 4-(1,2,3-Triazol
      4-yl)benzenediazonium-beta-CD tetrafluoroborate (pDz-beta-CD) and 3-(1,2,3
      triazol-4-yl)benzenediazonium-beta-CD tetrafluoroborate (mDz-beta-CD) were
      successfully prepared by Cu((I))-catalyzed azide alkyne coupling (CuAAC) of 6
      monodeoxy-6-monoazido-beta-cyclodextrin (N(3)-beta-CD) and 4-ethynylaniline and 3
      ethynylaniline, respectively, followed by diazotization. The products were
      isolated and stored successfully for several months at -18  degrees C. The
      intermediates and products were verified by Attenuated Total Reflectance Fourier
      Transform Infrared, Nuclear Magnetic Resonance, and Heteronuclear Single Quantum
      Coherence. pDz-beta-CD and mDz-beta-CD were immobilized onto glassy carbon and
      gold surfaces facilitated by electrochemical reduction of the diazonium group.
      The thus generated aryl radical reacted with the surface. The modified gold
      surfaces were investigated by Polarization Modulation Infrared Reflection
      Absorption Spectroscopy and cyclic voltammetry employing the redox probe
      K(3)Fe(CN)(6) to analyze the extent of blocking of the surfaces. Finally, the
      availability of the cavity of surface-immobilized beta-CD was shown by
      complexation of ferrocene followed by cyclic voltametric analysis.

PMID- 23163592
TI  - Meta-analysis: Barrett's oesophagus and the risk of colonic tumours.
AB  - BACKGROUND: Barrett's oesophagus (BO) is a premalignant condition associated with
      oesophageal adenocarcinoma. Although speculation exists, it is currently unclear
      if BO is associated with an increased risk of colonic tumours. AIM: To conduct a
      meta-analysis of studies reporting the prevalence of colonic tumours in patients
      with BO vs. controls and thus quantify the risk of colonic tumours associated
      with BO. METHODS: A search was conducted through Medline, PubMed, Embase, and
      Current Contents Connect to 7 October 2012. We calculated pooled odds ratios (OR)
      and 95% confidence intervals (CI) using a random-effects model for the risk of
      all colonic tumours associated with BO, as well as for the subgroups of
      colorectal cancer (CRC) and benign adenomatous tumours. RESULTS: In total, 11
      studies, with 2580 BO cases, met our inclusion criteria. BO was associated with
      an increased risk of any colonic tumours (OR: 1.96; 95% CI: 1.56-2.46). BO was
      associated with an increased risk of benign adenomatous tumours (OR: 1.69; 95%
      CI: 1.20-2.39), as well as an increased risk of CRC (OR: 1.90; 95% CI: 1.35
      2.67). No statistically significant heterogeneity was observed. Publication bias
      was not present. CONCLUSIONS: Barrett's oesophagus was associated with an
      increased risk of both benign adenomatous colonic tumours and colorectal cancer.
      Barrett's oesophagus had a stronger association with colorectal cancer than with
      benign colonic tumours. Further prospective cohort studies are needed to confirm
      the relationship.

PMID- 23163593
TI  - Metacommunity structure in a small boreal stream network.
AB  - Current ecological frameworks emphasize the relative importance of local and
      regional drivers for structuring species communities. However, most research has
      been carried out in systems with discrete habitat boundaries and a clear insular
      structure. Stream networks deviate from the insular structure and can serve as
      excellent model systems for studying hierarchical community dynamics over
      different temporal and spatial extents. We used benthic invertebrate data from
      streams in a small northern Swedish catchment to test whether metacommunity
      dynamics change between seasons, across spatial hierarchies (i.e. at the whole
      catchment scale vs. the scales of first-order and second/third-order sites within
      the catchment) and between stream-order groups. We assessed metacommunity
      structure as a function of three relevant dispersal dimensions (directional
      downstream processes, along-stream dispersal and overland dispersal). These
      dispersal dimensions were related to species groups with relevant dispersal
      traits (flying capacity, drift propensity) and dispersal capacities (weak vs.
      strong) to elucidate whether the observed spatial signals were due to dispersal
      limitation or mass effects. Results showed complex community organization that
      varied between seasons, with the scale of observation, and with stream order. The
      importance of spatial factors and specific dispersal dimensions was highly
      dependent on the time of sampling and the scale of observation. The importance of
      environmental factors was more consistent in our analyses, but their effect on
      species community structure peaked at first-order sites. Our analyses of species
      dispersal traits were not unequivocal, but indicated that both mass effects and
      dispersal limitation could simultaneously contribute to the spatial signal at the
      scale of the whole catchment through different dispersal pathways. We conclude
      that the study of hierarchically organized ecosystems uncovers complex patterns
      of metacommunity organization that may deviate substantially from those of
      systems with insular structure and discrete habitat boundaries. Moreover, we show
      that dispersal constraints imposed by the dendritic structure of stream networks
      and distinct dispersal mechanisms (e.g. dispersal limitation) may be evident also
      at very small spatial extents. Thus, even at this small scale, a landscape
      management approach that takes the dendritic nature of stream networks into
      account is needed to effectively conserve stream biodiversity. 

PMID- 23163594
TI  - Hydroxocobalamin in cyanide poisoning.
AB  - INTRODUCTION: On theoretical grounds, hydroxocobalamin is an attractive antidote
      for cyanide poisoning as cobalt compounds have the ability to bind and detoxify
      cyanide. This paper reviews the pharmacokinetic and pharmacodynamic aspects of
      hydroxocobalamin, its efficacy in human cyanide poisoning and its adverse
      effects. METHODS: PubMed was searched for the period 1952 to April 2012. A total
      of 71 papers were identified in this way; and none was excluded. PHARMACOKINETICS
      AND PHARMACODYNAMICS: Pharmacokinetic studies in dogs and humans suggest a two
      compartment model, with first order elimination kinetics. Pharmacodynamic studies
      in animals suggest that hydroxocobalamin would be a satisfactory antidote for
      human cyanide poisoning. EFFICACY IN HUMAN POISONING: There is limited evidence
      that hydroxocobalamin alone is effective in severe poisoning by cyanide salts.
      The evidence for the efficacy of hydroxocobalamin in smoke inhalation is
      complicated by lack of evidence for the importance of cyanide exposure in fires
      and the effects of other chemicals as well as confounding effects of other
      therapeutic measures, including hyperbaric oxygen. Evidence that hydroxocobalamin
      is effective in poisoning due to hydrogen cyanide alone is lacking; extrapolation
      of efficacy from poisoning by ingested cyanide salts may not be valid. The rate
      of absorption may be greater with inhaled hydrogen cyanide and the recommended
      slow intravenous administration of hydroxocobalamin may severely limit its
      clinical effectiveness in these circumstances. ADVERSE EFFECTS: Both animal and
      human data suggest that hydroxocobalamin is lacking in clinically significant
      adverse effects. However, in one human volunteer study, delayed but prolonged
      rashes were observed in one-sixth of subjects, appearing 7 to 25 days after
      administration of 5 g or more of hydroxocobalamin. Rare adverse effects have
      included dyspnoea, facial oedema, and urticaria. CONCLUSIONS: Limited data on
      human poisonings with cyanide salts suggest that hydroxocobalamin is an effective
      antidote; data from smoke inhalation are less clear-cut. Although clinically
      important reactions to hydroxocobalamin have not been seen, some, non-life
      threatening, adverse reactions can occur.

PMID- 23163595
TI  - Impaired bactericidal but not fungicidal activity of polymorphonuclear
      neutrophils in patients with chronic lymphocytic leukemia.
AB  - We examined the qualitative polymorphonuclear neutrophil (PMN)-associated immune
      impairment in patients with chronic lymphocytic leukemia (CLL) by characterizing
      phagocytic killing of key non-opsonized bacterial (Staphylococcus aureus and
      Pseudomonas aeruginosa) and fungal (Candida albicans and Aspergillus fumigatus)
      pathogens. Neutrophils were collected from 47 non-neutropenic patients with CLL
      (PMN count > 1000/mm(3)) and age-matched and young healthy controls (five each).
      A subset of patients (13%) had prior or subsequent infections. We found that the
      patients with CLL had diminished PMN microbicidal response against bacteria but
      not against fungi compared with the controls. Compared to patients with effective
      PMN responses, we did not identify differences of basal PMN pathogen-associated
      molecular pattern receptor gene expression, soluble pathogen-associated molecular
      pattern gene expression or inflammatory cytokine signatures in patients with
      impaired PMN responses when PMNs were analyzed in multiplex real-time polymerase
      chain reaction assays. However, differences in PMN microbicidal response against
      A. fumigatus in patients with CLL were associated with the degree of
      hypogammaglobulinemia.

PMID- 23163597
TI  - Hydrophobic and hydrophilic associations of a methanol pair in aqueous solution.
AB  - The association dynamics of a methanol pair in aqueous solution were
      theoretically studied with QM/EFP-MD and quantum mechanical methods. Stable
      contact pairs and solvent separated configurations (SS) were found from
      simulations with a free energy barrier of 2 kcal/mol, revealing the strong
      tendency of methanol association. The stable contact pairs were further
      identified as the hydrophobic (CP(A)) and hydrophilic (CP(B)) species, with the
      CP(A) having a larger population. Although the free energy difference between the
      CP(A) and CP(B) is negligible with virtually no associated free energy barrier,
      the slow isomerization dynamics of intermolecular rotations ensures their
      individual identity. Further mechanistic analysis revealed that only the CP(A)
      has a direct path to the SS, showing that hydrophobic attraction initiates the
      association process. A subsequent intermolecular hydrophilic attraction
      isomerizes CP(A) and CP(B). Therefore, our results show that both the hydrophobic
      and hydrophilic attractions between methanol molecules play important roles in
      the association dynamics. The former operates on the longer intermolecular
      distance, while the latter is effective in contact pairs.

PMID- 23163596
TI  - Stability of nucleosomes containing homogenously ubiquitylated H2A and H2B
      prepared using semisynthesis.
AB  - Post-translational modifications (PTMs) of histones are an essential feature in
      the dynamic regulation of chromatin. One of these modifications, ubiquitylation,
      has been speculated to directly influence the stability of the nucleosome, which
      represents the basic building block of chromatin. Here we report a strategy for
      the semisynthesis of site-specifically ubiquitylated histone H2A (uH2A). This
      branched protein was generated through a three-piece expressed protein ligation
      approach including a traceless ligation at valine. uH2A could be efficiently
      incorporated into nucleosomes, thereby opening the way to detailed biochemical
      and biophysical studies on the function of this PTM. Accordingly, we used uH2A,
      as well as a previously generated ubiquitylated H2B, in chaperone-coupled
      nucleosome stability assays to demonstrate that the direct effect of
      ubiquitylated histones on nucleosomal stability is in fact modest.

PMID- 23163598
TI  - An alarming trend within the biological/biomedical research literature toward the
      citation of review articles rather than the primary research papers.

PMID- 23163599
TI  - Successful tocilizumab treatment in a patient with human herpesvirus 8-positive
      and human immunodeficiency virus-negative multicentric Castleman's disease of
      plasma cell type nonresponsive to rituximab-CVP therapy.
AB  - We present and discuss the case of a HIV-negative female finally diagnosed upon
      histopathologic and molecular biologic evaluations with human herpesvirus 8
      (HHV8)-positive multicentric Castleman's disease (MCD) of plasma cell type, but
      with no detectable HHV8-DNA in peripheral blood. She failed to respond to
      combination immunosuppressive therapeutic trials of corticosteroids and
      azathioprine, and neither an immunochemotherapy of rituximab-CVP (R-CVP) induced
      disease resolution. However, monoclonal anti-IL-6R antibody (tocilizumab)
      immunotherapy resulted in beneficial disease stabilization. A control lymph node
      biopsy indicated mild polyclonal plasmacytosis, and a negative HHV8
      determination. The patient is still receiving tocilizumab. This case emphasizes
      the individual nature of MCD requiering more personalized disease management.

PMID- 23163600
TI  - Forces of interactions between bare and polymer-coated iron and silica: effect of
      pH, ionic strength, and humic acids.
AB  - The interactions between a silica substrate and iron particles were investigated
      using atomic force microscopy-based force spectroscopy (AFM). The micrometer- and
      nanosized iron particles employed were either bare or coated with carboxymethyl
      cellulose (CMC), a polymer utilized to stabilize iron particle suspensions. The
      effect of water chemistry on the forces of interaction was probed by varying
      ionic strength (with 100 mM NaCl and 100 mM CaCl2) or pH (4, 5.5, and 8) or by
      introducing 10 mg/L of humic acids (HA). When particles were uncoated, the forces
      upon approach between silica and iron were attractive at pH 4 and 5.5 and in 100
      mM CaCl2 at pH 8, but they were negligible in 100 mM NaCl buffered to pH 8 and
      repulsive in water buffered to pH 8 and in HA solutions. HA produced
      electrosteric repulsion between iron particles and silica, likely due to its
      sorption to iron particles. HA sorption to silica was excluded on the basis of
      experiments conducted with a quartz-crystal microbalance with dissipation
      monitoring. Repulsion with CMC-coated iron was attributed to electrosteric
      forces, which were damped at high ionic strength. An extended DLVO model and a
      modified version of Ohshima's theory were successfully utilized to model AFM
      data.

PMID- 23163601
TI  - An algorithm for genetic testing of Serbian patients with demyelinating Charcot
      Marie-Tooth.
AB  - Charcot-Marie Tooth (CMT) is a clinically and genetically heterogeneous group of
      diseases with rough genotype-phenotype correlation, so the final diagnosis
      requires extensive clinical and electrophysiological examination, family data,
      and gene mutation analysis. Although there is a common pattern of genetic basis
      of CMT, there could be some population differences that should be taken into
      account to facilitate analyses. Here we present the algorithm for genetic testing
      in Serbian patients with demyelinating CMT, based on their genetic specificities:
      in cases of no PMP22 duplication, and if -X-linked CMT (CMTX) is not
      contraindicated by pattern of inheritance (male-to-male transmission), one should
      test for c.94A>G GJB founder mutation, first. Also, when a patient is of Romani
      ethnicity, or if there is an autosomal recessive inheritance in a family and
      unclear ethnicity, c.442C>T mutation in NDRG1 should be tested.

PMID- 23163602
TI  - Roles of IL-10 in ocular inflammations: a review.
AB  - INTRODUCTION: This review represents the current in vitro, in vivo, animal and
      human investigations on the roles of IL-10 in ocular inflammatory conditions.
      MATERIALS AND METHODS: The data sources were literature reviews, including Pub
      Med, Medline, and ISI databases (since 1989 to mid-2012). Search items were, IL
      10, chemokines, cytokines, alone or in combination with, serum, aqueous, vitreous
      eye, ocular, ocular tissues, ophthalmic, and review. RESULTS: Ocular effects of
      IL-10 depend on the sources of the secretion and sites of the action. IL-10 plays
      important anti-inflammatory and especially anti-angiogenic activities in ocular
      tissues such as the conjunctiva, cornea, retina, choroid, and orbit. CONCLUSION:
      IL-10 plays major anti-inflammatory and anti-angiogenic roles in most of the
      ocular inflammations. Also, IL-10 plays a role in development of anterior chamber
      associated immune deviation (ACAID). Any manipulation of IL-10 for treatment
      purposes should be considered very cautiously due to its potential hazards to the
      immune system.

PMID- 23163603
TI  - Predictors of neurological outcome in cooled neonates.
AB  - BACKGROUND: We define clinical predictors of neurological outcome in neonates
      with hypoxic-ischemic encephalopathy undergoing hypothermia therapy. METHODS:
      Twenty-one neonates who underwent selective head cooling between 2004 and 2010
      and were followed neurologically for >= 24 months were investigated
      retrospectively. Patients were divided according to the neurological outcome at 2
      years of age into group A (n = 11), patients with normal neurological function,
      and group B (n = 10), patients with neurological disabilities (n = 9) or those
      who died (n = 1). Predictors were determined by chi(2) and Mann-Whitney U-tests,
      anova, Spearman rank correlations and receiver-operator curves. RESULTS: Group B
      showed higher average blood lactate levels during the first day, particularly at
      24 h of life; lower day-3 cerebral blood flow resistance index; higher maximum
      dobutamine dose used; higher rate of thiamylal sodium used; more severe
      background electroencephalogram suppression during the first week (group A: 11/11
      cases <= grade 3; group B: 7/9 cases at grade 4-5) and higher rate of cerebral
      lesions on magnetic resonance imaging in the second week (group A: 1/11 case;
      group B: 9/10 cases) than group A. The most useful predictor of poor prognosis
      was cerebral parenchymal lesions on magnetic resonance imaging with 90%, 90% and
      90% of sensitivity, specificity and accuracy, followed by week-1 background
      electroencephalogram >= grade 4 with 70%, 100% and 85% and day-3 cerebral blood
      flow resistance index < 0.46 with 71%, 88% and 80%, respectively. CONCLUSIONS:
      Prediction of post-cooling neurological outcome could be improved substantially
      by evaluating multiple factors.

PMID- 23163604
TI  - A novel glutathione-hydroxycinnamic acid product generated in oxidative wine
      conditions.
AB  - This study characterizes a novel glutathione-substituted dihydroxyphenyl compound
      formed during the oxidation of white wine and model wine solutions, which may
      contribute to the synergistic role of glutathione and hydroxycinnamic acids in
      delaying oxidative coloration. The critical components for the formation of the
      compound were found to be hydroxycinnamic acids and glutathione, while ascorbic
      acid enabled the product to accumulate to higher concentrations. The presence of
      the wine components important in other wine oxidation mechanisms, (+)-catechin,
      ethanol and/or tartaric acid, was not essential for the formation of this new
      compound. Via LC-MS/MS, HR-MS and (1)H NMR (1D and 2D NMR) analyses, the major
      isomer of the compound formed from glutathione and caffeic acid was found to be 4
      [(E)-2'-(S)-glutathionyl ethenyl]-catechol (GEC). Equivalent products were also
      confirmed via LC-MS/MS for other hydroxycinnamic acids (i.e., ferulic and
      coumaric acids). Only trace amounts of GEC were formed with the quinic ester of
      caffeic acid (i.e., chlorogenic acid), and no equivalent product was found for
      cinnamic acid. GEC was detected in a variety of white wines supplemented with
      glutathione and caffeic acid. A radical mechanism for the formation of the
      styrene-glutathione derivatives is proposed.

PMID- 23163605
TI  - Underage drinkers' responses to negative-restrictive versus proactive
      nonrestrictive slogans in humorous anti-alcohol abuse messages: are humorous
      responsible drinking campaign messages effective?
AB  - This study examined underage drinkers' responses to negative-restrictive versus
      proactive-nonrestrictive slogans in humorous anti-alcohol abuse advertisements.
      The authors conducted a posttest-only control group experiment with 91 teenagers
      and college-aged participants. For underage moderate drinkers, the negative
      restrictive slogans (e.g., "Don't drink") increased participants' perceived risk
      of excessive drinking and increased a level of intention to change their drinking
      behavior. However, for underage binge drinkers, the negative-restrictive slogans
      lowered participants' risk perception of excessive drinking and intention to
      change their drinking behavior.

PMID- 23163606
TI  - Overexpression of enhancer of zeste homolog 2 and MUC1 may be related to
      malignant behaviour in intraductal papillary neoplasm of the bile duct.
AB  - AIMS:   Intraductal papillary neoplasm of the bile duct (IPNB) usually has a
      favourable prognosis, but occasionally is associated with invasive carcinoma.
      Overexpression of the polycomb group protein enhancer of zeste homolog 2 (EZH2)
      is involved in the progression of malignant tumours. In this study, we examined
      the significance of EZH2 expression in IPNB and its association with
      clinicopathological features and the expression of p16(INK4a) , p53 and mucin
      core proteins. METHODS AND RESULTS:   We examined immunohistochemically the
      expression of EZH2, p16(INK4a) , MUC mucin core proteins and p53 in 15 patients
      with IPNB without invasion, including the cystic variant [male/female ratio (M/F)
      = 9/6], and in 19 with IPNB associated with invasive carcinoma (M/F = 13/6). The
      expression levels of EZH2, p53 and MUC1 were significantly lower (P < 0.01), and
      of MUC6 were significantly higher (P < 0.05), in IPNB without invasion than in
      IPNB with invasion. Expression of EZH2 was significantly correlated with
      expression of MUC1 (P < 0.01) and inversely correlated with expression of MUC6 (P
      < 0.05). In cholangiocarcinoma cells (HuCTT-1 and TFK-1), knockdown of EZH2 and
      MUC1 by small interfering RNA decreased invasion and proliferation, whereas
      knockdown of MUC6 increased invasion. CONCLUSIONS:   Overexpression of EZH2 may
      be associated with malignant behaviour in IPNB in parallel with up-regulated MUC1
      expression and down-regulated MUC6 expression.

PMID- 23163607
TI  - Cellular and humoral immune responses of Senegalese sole, Solea senegalensis
      (Kaup), following challenge with two Photobacterium damselae subsp. piscicida
      strains from different geographical origins.
AB  - The present study aimed to investigate leucocyte responses to inflammation as
      well as some innate immune parameters of Senegalese sole, Solea senegalensis,
      following challenge with two strains of Photobacterium damselae subsp. piscicida
      belonging to the European and Japanese clones described for this bacterium.
      Pathogenicity assays were performed to assess the virulence of each
      Photobacterium damselae subsp. piscicida strain for sole. Subsequently, fish were
      intraperitoneally injected with phosphate-buffered saline (control) or two
      concentrations (2 * 102 and 2 * 106 CFU mL-1) of each bacterial strain and
      sampled after 6 and 24 h. Results showed that the European isolate induces a
      higher degree of response than the Japanese strain. While blood neutrophilia and
      monocytosis correlated well with the increase in neutrophil and macrophage
      numbers in the peritoneal cavity, fish infected with the European isolate
      presented higher peritoneal cell numbers than fish challenged with the Japanese
      strain. In addition, alternative complement pathway activity and respiratory
      burst of head kidney leucocytes increased significantly in fish infected with the
      European isolate. The enhanced innate immune response displayed by Senegalese
      sole challenged with the European isolate is probably due to the higher degree of
      virulence presented by this Photobacterium damselae subsp. piscicida strain.

PMID- 23163608
TI  - High mobility indium zinc oxide thin film field-effect transistors by
      semiconductor layer engineering.
AB  - Indium zinc oxide thin-film transistors are fabricated via a precursor in
      solution route on silicon substrates with silicon dioxide gate dielectric. It is
      found that the extracted mobility rises, peaks, and then decreases with
      increasing precursor concentration instead of rising and saturating.
      Investigation with scanning probe techniques reveals full thickness variations
      within the film which are assumed to adversely affect charge transport.
      Additional layers are coated, and the extracted mobility is observed to increase
      up to 19.7 cm(2) V(-1) s(-1). The reasons for this are examined in detail by
      direct imaging with scanning tunneling microscopy and extracting electron density
      profiles from X-ray reflection measurements. It is found that the optimal
      concentration for single layer films is suboptimal when coating multiple layers
      and in fact using many layers of very low concentrations of precursor in the
      solution, leading to a dense, defect and void free film, affording the highest
      mobilities. A consistent qualitative model of layer formation is developed
      explaining how the morphology of the film develops as the concentration of
      precursor in the initial solution is varied.

PMID- 23163609
TI  - Matrix isolation infrared and DFT study of the trimethyl phosphite-hydrogen
      chloride interaction: hydrogen bonding versus nucleophilic substitution.
AB  - Trimethyl phosphite (TMPhite) and hydrogen chloride (HCl), when separately
      codeposited in a N(2) matrix, yielded a hydrogen bonded adduct, which was
      evidenced by shifts in the vibrational frequencies of the TMPhite and HCl
      submolecules. The structure and energy of the adducts were computed at the B3LYP
      level using 6-31++G** and aug-cc-pVDZ basis sets. While our computations
      indicated four minima for the TMPhite-HCl adducts, only one adduct was
      experimentally identified in the matrix at low temperatures, which interestingly
      was not the structure corresponding to the global minimum, but was the structure
      corresponding to the first higher energy local minimum. The Onsager self
      consistent reaction field model was used to explain this observation. In an
      attempt to prepare the hydrogen bonded adduct in the gas phase and then trap it
      in the matrix, TMPhite and HCl were premixed prior to deposition. However, in
      these experiments, no hydrogen bonded adduct was observed; on the contrary,
      TMPhite reacted with HCl to yield CH(3)Cl, following a nucleophilic substitution,
      a reaction that is apparently frustrated in the matrix.

PMID- 23163610
TI  - Quantum dots at room temperature carved out from few-layer graphene.
AB  - We present graphene quantum dots endowed with addition energies as large as 1.6
      eV, fabricated by the controlled rupture of a graphene sheet subjected to a large
      electron current in air. The size of the quantum dot islands is estimated to be
      in the 1 nm range. The large addition energies allow for Coulomb blockade at room
      temperature, with possible application to single-electron devices.

PMID- 23163611
TI  - Calling and life satisfaction: it's not about having it, it's about living it.
AB  - The present study examined the relation of career calling to life satisfaction
      among a diverse sample of 553 working adults, with a specific focus on the
      distinction between perceiving a calling (sensing a calling to a career) and
      living a calling (actualizing one's calling in one's current career). As
      hypothesized, the relation of perceiving a calling to life satisfaction was fully
      mediated by living a calling. On the basis of this finding, a structural equation
      model was tested to examine possible mediators between living a calling and life
      satisfaction. As hypothesized, the relation of living a calling to life
      satisfaction was partially mediated by job satisfaction and life meaning, and the
      link between living a calling and job satisfaction was mediated by work meaning
      and career commitment. Modifications of the model also revealed that the link of
      living a calling to life meaning was mediated by work meaning. Implications for
      research and practice are discussed.

PMID- 23163612
TI  - A meta-analysis of acculturation/enculturation and mental health.
AB  - This meta-analytic study examined the relationship among the constructs of
      acculturation, enculturation, and acculturation strategies (i.e., integration,
      assimilation, separation, marginalization), and mental health. Data from 325
      studies (163 journal articles and 162 dissertation studies) were analyzed using a
      random-effects model, across a broad spectrum of negative mental health (NM:
      depression, anxiety, psychological distress, and negative affect) and positive
      mental health (PM: self-esteem, satisfaction with life, and positive affect).
      Overall, acculturation was favorably associated with both NM (negatively) and PM
      (positively), whereas enculturation was favorably related only to PM
      (positively). In fact, enculturation was positively related to anxiety. The
      specifics of these relations were further examined using the following
      moderators: (a) researchers' operationalization of acculturation/enculturation
      (i.e., linearity, dimensionality); (b) contextual influences (i.e., when and
      where the study was conducted); and (c) sample characteristics (i.e.,
      voluntariness of residency, race, gender, age). Overall, bilinear measures of
      acculturation indicated a positive association with PM, while unilinear measures
      did not. External acculturation (e.g., language, behaviors) and internal
      enculturation (e.g., identity) were most favorably related to mental health. The
      place of study had differential effects on the relation of enculturation and NM.
      Acculturation appeared to be especially important to Asian Americans, whereas
      enculturation was to African Americans. Differential effects of age suggested the
      need to consider life-span development of needs and social roles in relation to
      acculturation and enculturation. Both correlational analyses and mean comparisons
      affirmed that integration was the most favorable acculturation strategy to mental
      health. Implications for research, practice, and theory are discussed.

PMID- 23163613
TI  - Examining a model of life satisfaction among unemployed adults.
AB  - The present study examined a model of life satisfaction among a diverse sample of
      184 adults who had been unemployed for an average of 10.60 months. Using the Lent
      (2004) model of life satisfaction as a framework, a model was tested with 5
      hypothesized predictor variables: optimism, job search self-efficacy, job search
      support, job search behaviors, and work volition. After adding a path in the
      model from optimism to work volition, the hypothesized model was found to be a
      good fit for the data and a better fit than a more parsimonious, alternative
      model. In the hypothesized model, optimism, work volition, job search self
      efficacy, and job search support were each found to significantly relate to life
      satisfaction, accounting for 35% of the variance. Additionally, using 50,000
      bootstrapped samples, optimism was found to have a significant indirect effect on
      life satisfaction as mediated by job search self-efficacy, job search support,
      and work volition. Implications for research and practice are discussed.

PMID- 23163614
TI  - Catalysis of dioxygen reduction by Thermus thermophilus strain HB27 laccase on
      ketjen black electrodes.
AB  - We present electrochemical analyses of the catalysis of dioxygen reduction by
      Thermus thermophilus strain HB27 laccase on ketjen black substrates. Our cathodes
      reliably produce 0.56 mA cm(-2) at 0.0 V vs Ag|AgCl reference at 30  degrees C in
      air-saturated buffer, under conditions of nonlimiting O(2) flux. We report the
      electrochemical activity of this laccase as a function of temperature, pH, time,
      and the efficiency of its conversion of dioxygen to water. We have measured the
      surface concentration of electrochemically active species, permitting the
      extraction of electron transfer rates at the enzyme-electrode interface: 1 s(-1)
      for this process at zero driving force at 30  degrees C and a limiting rate of 23
      s(-1) at 240 mV overpotential at 50  degrees C.

PMID- 23163615
TI  - Self assembly of pH-sensitive cationic lysine based surfactants.
AB  - Three cationic surfactants of the type N(epsilon)-acyl lysine methyl ester
      hydrochloride have been studied with respect to solution behavior and adsorption
      on the air/water interface, as well as the thermolyotropic behavior. The self
      assembly of these surfactants, which have the cationic charge on amine protonated
      groups, was assessed by different physicochemical methods. Depending on the pH
      value, these surfactants can dissociate in aqueous solutions, losing the cationic
      charge. Therefore, knowledge of the pK(a) of these compounds is essential to
      explain their behavior in aqueous solutions. The bulk techniques, conductivity,
      and nuclear magnetic resonance diffusion (NMR) obtained similar critical micellar
      concentration (CMC) values, which were well above those obtained from surface
      tension. Surface tension measurements were strongly dependent on the technique
      used, namely, Wilhelmy plate and pendant drop. The phase behavior at medium to
      high concentrations has been studied by optical polarizing microscopy and small
      angle x-ray scattering (SAXS). The X-ray studies showed that the lysine-based
      surfactants at low hydration have rich thermotropic liquid crystalline behavior.
      The results are discussed in terms of the structure of the compounds and the
      cationic charge of the molecule. We will show how apparently small changes in
      molecule structure have a large influence on phase behavior.

PMID- 23163616
TI  - Larazotide acetate in patients with coeliac disease undergoing a gluten
      challenge: a randomised placebo-controlled study.
AB  - BACKGROUND: Coeliac disease, an autoimmune disorder triggered by gluten
      ingestion, is managed by a gluten-free diet (GFD), which is difficult for many
      patients. Larazotide acetate is a first-in-class oral peptide that prevents tight
      junction opening, and may reduce gluten uptake and associated sequelae. AIM: To
      evaluate the efficacy and tolerability of larazotide acetate during gluten
      challenge. METHODS: This exploratory, double-blind, randomised, placebo
      controlled study included 184 patients maintaining a GFD before and during the
      study. After a GFD run-in, patients were randomised to larazotide acetate (1, 4,
      or 8 mg three times daily) or placebo and received 2.7 grams of gluten daily for
      6 weeks. Outcomes included an experimental biomarker of intestinal permeability,
      the lactulose-to-mannitol (LAMA) ratio and clinical symptoms assessed by
      Gastrointestinal Symptom Rating Scale (GSRS) and anti-transglutaminase antibody
      levels. RESULTS: No significant differences in LAMA ratios were observed between
      larazotide acetate and placebo groups. Larazotide acetate 1-mg limited gluten
      induced symptoms measured by GSRS (P = 0.002 vs. placebo). Mean ratio of anti
      tissue transglutaminase IgA levels over baseline was 19.0 in the placebo group
      compared with 5.78 (P = 0.010), 3.88 (P = 0.005) and 7.72 (P = 0.025) in the
      larazotide acetate 1-, 4-, and 8-mg groups, respectively. Adverse event rates
      were similar between larazotide acetate and placebo groups. CONCLUSIONS:
      Larazotide acetate reduced gluten-induced immune reactivity and symptoms in
      patients with coeliac disease undergoing gluten challenge and was generally well
      tolerated; however, no significant difference in LAMA ratios between larazotide
      acetate and placebo was observed. Results and design of this exploratory study
      can inform the design of future studies of pharmacological interventions in
      patients with coeliac disease.

PMID- 23163617
TI  - Simultaneous detection of multiple designer drugs in serum, urine, and CSF in a
      patient with prolonged psychosis.
AB  - This case report is considered exempt from University of California-San Diego
      Investigational Review Board. INTRODUCTION: There is a limited published
      experience detailing detection and toxicity of multiple novel psychoactive
      substances. We report a case of a patient with prolonged psychosis who had JWH
      072, cannabicyclohexanol, 3',4'-methylenedioxy-alpha-pyrrolidinopropiophenone
      (MDPPP) and methylenedioxyamphetamine (MDA) identified in multiple biological
      samples. CASE DETAILS: An 18-year-old man presented to the emergency department
      (ED) with acute onset psychosis after allegedly smoking "spice." Due to agitation
      and psychosis refractory to multiple medications, a lumbar puncture was performed
      and he was admitted. All blood, urine, and CSF (cerebral spinal fluid) testing
      was normal. He remained psychotic for almost 1 week. MDPPP, JWH-072 and MDA were
      detected in initial blood, urine, and CSF samples. Cannabicyclohexanol was
      detected only in his serum. DISCUSSION AND CONCLUSION: JWH-072 is a cannabinoid-2
      receptor (CB-2) agonist which has not been reported previously in the literature.
      Its clinical effects are unknown. Cannabicyclohexanol is a known component of
      "spice" products and has been associated with agitation and psychosis. MDPPP and
      MDA are designer phenylethylamines likely to cause agitation and sympathomimetic
      symptoms. Simultaneous detection of novel psychoactive substances in multiple
      biological fluids has not been previously reported. This case suggests that the
      interaction of these particular substances may be associated with prolonged
      psychosis.

PMID- 23163618
TI  - Randomized controlled study on the use of multiple-dose activated charcoal in
      patients with supratherapeutic phenytoin levels.

PMID- 23163619
TI  - Remote control of lipophilic nucleic acids domain partitioning by DNA
      hybridization and enzymatic cleavage.
AB  - Lateral partitioning of lipid-modified molecules between liquid-disordered (ld)
      and liquid-ordered (lo) domains depends on the type of lipid modification,
      presence of a spacer, membrane composition, and temperature. Here, we show that
      the lo domain partitioning of the palmitoylated peptide nucleic acid (PNA) can be
      influenced by formation of a four-component complex with the ld domain
      partitioning tocopherol-modified DNA: the PNA-DNA complex partitioned into the ld
      domains. Enzymatic cleavage of the DNA linker led to the disruption of the
      complex and restored the initial distribution of the lipophilic nucleic acids
      into the respective domains. This modular system offers strategies for dynamic
      functionalization of biomimetic surfaces, for example, in nanostructuring and
      regulation of enzyme catalysis, and it provides a tool to study the molecular
      basis of controlled reorganization of lipid-modified proteins in membranes, for
      example, during signal transduction.

PMID- 23163620
TI  - Mitochondrial DNA variation is associated with elite athletic status in the
      Polish population.
AB  - There is mounting evidence that genetic factors located in mitochondrial and
      nuclear genomes influence sport performance. Certain mitochondrial haplogroups
      and polymorphisms were associated with the status of elite athlete, especially in
      endurance performance. The aim of our study was to assess whether selected
      mitochondrial DNA (mtDNA) and nuclear DNA variants are associated with elite
      athlete performance in a group of 395 elite Polish athletes (213 endurance
      athletes and 182 power athletes) and 413 sedentary controls. Our major finding
      was that the mtDNA haplogroup H and HV cluster influence endurance performance at
      the Olympic/World Class level of performance (P = 0.018 and P = 0.0185,
      respectively). We showed that two polymorphisms located in the mtDNA control
      region were associated with achieving the elite performance level either in the
      total athlete's group as compared with controls (m.16362C, 3.8% vs 9.2%,
      respectively, P = 0.0025, odds ratio = 0.39, 95% confidence interval: 0.21-0.72),
      or in the endurance athletes as compared with controls (m.16080G, 2.35% vs 0%,
      respectively, P = 0.004). Our results indicate that mtDNA variability affects the
      endurance capacity rather than the power one. We also propose that mtDNA
      haplogroups and subhaplogroups, as well as individual mtDNA polymorphisms
      favoring endurance performance, could be population-specific, reflecting complex
      cross-talk between nuclear and mitochondrial genomes.

PMID- 23163621
TI  - Influences of glucose on the dietary hydroxyflavonoid-plasma protein interaction.
AB  - The influence of glucose on the interaction between flavonoids and plasma
      proteins from healthy humans (HPPs) was investigated. Glucose affected the
      flavonoid-protein interactions depending upon their structures. Glucose
      significantly reduced the affinities of HPPs for 6-hydroxyflavone by 10.72 times,
      slightly weakened the affinities of HPPs for quercetin, 7-hydroxyflavone, and
      kaempferol, and hardly affected the affinities of HPPs for myricetin, chrysin,
      and 3,7-dihydroxyflavone on the first day. However, glucose obviously enhanced
      the affinities of HPPs for 3-hydroxyflavone, luteolin, and apigenin. Glucose
      significantly weakened the binding affinities of HPPs for chrysin, kaempferol,
      quercetin, and myricetin by 6.17, 7.94, 14.12, and 112.2 times, when kept at 37 
      degrees C under air conditions for 14 days, and the binding affinities of HPPs
      for 7-hydroxyflavone, luteolin, 3,7-dihydroxyflavone, 3-hydroxyflavone, and 6
      hydroxyflavone were slightly decreased by 1.35-, 1.58-, 1.58-, 1.9-, and 2.4
      fold. The binding affinity between apigenin and HPP was hardly influenced.
      Glucose weakened the binding affinities of HPPs for hydroxyflavonoids. The
      differences between log K(a)(absence) and log K(a)(presence) were bigger for the
      more lipophilic hydroxyflavonoids, and more lipophilic hydroxyflavonoids are
      easily affected by glucose, when kept at 37  degrees C under air conditions for
      14 days. These flavonoids with lower hydrogen donor/acceptor numbers prefer to
      stably interact with HPPs in the presence of glucose. However, other flavonoids
      with high hydrogen donor/acceptor numbers (multi-hydroxyl flavonoids) were apt to
      reduce their affinities with HPPs in the presence of glucose.

PMID- 23163622
TI  - Ancillary testing, diagnostic/classification criteria and severity grading in
      Behcet disease.
AB  - Since there is no pathognomonic clinical sign or laboratory test to distinguish
      Behcet disease from other uveitic entities, the diagnosis must be made based on
      characteristic ocular and systemic findings in the absence of evidence of other
      disease that can explain the findings. Ancillary tests, including ocular and
      brain imaging studies, are used to assess the severity of intraocular
      inflammation and systemic manifestations of Behcet disease, to identify latent
      infections and other medical conditions that might worsen with systemic
      treatment, and to monitor for adverse effects of drugs used. There are two
      diagnostic or classification criteria in general use by the uveitis community,
      one from Japan and one from an international group; both rely on a minimum number
      and/or combination of clinical findings to identify Behcet disease. Finally,
      several grading schemes have been proposed to assess severity of ocular disease
      and response to treatment.

PMID- 23163623
TI  - Operatively treated traumatic versus non-traumatic rotator cuff ruptures: a
      registry study.
AB  - BACKGROUND: Operative treatment of traumatic rotator cuff ruptures, i.e. ruptures
      with a predisposing traumatic event, is reported to yield superior results
      compared to operative treatment of non-traumatic, degenerative ruptures. AIM: The
      purpose of this study was to evaluate the difference of outcome, peroperative
      findings, and demographics after operative treatment of traumatic versus non
      traumatic rotator cuff rupture. METHODS: A total of 306 consecutive shoulders
      with an operated rotator cuff rupture (124 traumatic and 182 non-traumatic) were
      followed up. Constant and Murley score, size of the rupture, and age of the
      patients were used as an outcome measure. RESULTS: A total of 112 traumatic and
      167 non-traumatic rotator cuff rupture shoulders were available for 1-year follow
      up (91%). Mean Constant and Murley score was preoperatively lower in the
      traumatic group (46 versus 52, P = 0.01). At 3 months postoperatively, Constant
      and Murley scores were 61 and 60 (P = 0.72) and at 1 year 73 and 77 (P = 0.03),
      respectively. Altogether 91% of the patients in the traumatic and 93% in the non
      traumatic group were satisfied with the final outcome (P = 0.45). In 94% of
      traumatic and 95% of a non-traumatic cases the rupture involved the supraspinatus
      tendon. In the traumatic group the rupture was larger and involved more
      frequently the whole supraspinatus insertion area (41% versus 17%, P < 0.0001).
      Mean age of patients was 58 and 57 years, respectively. CONCLUSION: Operative
      treatment of both traumatic and non-traumatic rotator cuff ruptures gives
      essentially good results. In our cohort, patients' recollection of predisposing
      trauma reflects the size of the rotator cuff rupture, but does not reflect the
      age of the patients.

PMID- 23163624
TI  - Thoracic radiculopathy caused by ossification of the ligamentum flavum.
AB  - Thoracic ossification of the ligamentum flavum (OLF) has been widely recognized
      as a main cause of thoracic myelopathy in Asia, particularly in Japan. However,
      thoracic OLF rarely causes radiculopathy. We report a rare case of thoracic
      radiculopathy caused by OLF. A 67-year-old male presented with a chief complaint
      of back pain radiating to the right of the abdomen. Neurological examination
      revealed mild sensory deficit at the right side of the abdomen at the T9-10
      level. Magnetic resonance imaging and computed tomography demonstrated OLF at the
      right T9-10 level. Thoracic radiculopathy caused by OLF was suspected. Because
      conservative treatment was not effective to this lesion, surgical intervention
      was performed, and the pain disappeared immediately after the operation. Thoracic
      OLF rarely causes radiculopathy, but it should be considered as a differential
      diagnosis of thoracic radicular pain. When conservative treatment is not
      effective in this lesion, surgical treatment should be considered.

PMID- 23163625
TI  - Oxygen free radical and antioxidant status in necrotizing soft tissue infection
      of the lower extremity; a report of two cases with opposite outcomes.
AB  - Two cases of necrotizing soft tissue infection of the lower extremity were
      treated concurrently but independently. Multimodal therapy including hip joint
      disarticulation and hyperbaric oxygen therapy was administered, resulting in
      opposite outcomes: survival and death. Analysis of the relationships between
      patient outcome and time-course changes in serum diacron-reactive oxygen
      metabolites (d-ROMs; an index of oxidative stress), antioxidative potential, and
      cytokines revealed that serum d-ROMs levels decreased with time, but high serum
      levels of interleukin-10 (anti-inflammatory cytokine) persisted in the patient
      who died. These findings may reflect an immunosuppressive status unfavorable to
      infection prevention. Serum d-ROMs may be a prognostic predictor in necrotizing
      soft tissue infections.

PMID- 23163626
TI  - PAX8 and PAX5 are differentially expressed in B-cell and T-cell lymphomas.
AB  - AIMS:   The purpose of this study was to evaluate the expression patterns of B
      cell specific activator protein (BSAP)/PAX5 and PAX8 in a wide variety of B-cell
      and T-cell neoplasms. METHODS AND RESULTS:   A wide range of B-cell and T-cell
      neoplasms were subjected to immunohistochemical staining with antibodies against
      BSAP/PAX5 and PAX8 (polyclonal, pPAX8; monoclonal, mPAX8). Ten non-neoplastic
      lymph node specimens were examined with the same panel. All of the tested
      neoplastic and non-neoplastic B-cells reacted with the BSAP/PAX5 and pPAX8
      antibodies, but did not show reactivity with the mPAX8 antibody. All tested T
      cell neoplasms were negative using the BSAP/PAX5, pPAX8 and mPAX8 antibodies.
      CONCLUSIONS:   This is the first study to show the absence of reactivity to an
      mPAX8 antibody in an expanded panel of B-cell lymphomas as well as in a variety
      of T-cell neoplasms. In contrast to the mPAX8 antibody, the pPAX8 antibody shows
      nuclear positivity in non-neoplastic B cells and mature B-cell neoplasms;
      however, this expression is probably a result of cross-reactivity with PAX5.
      Given that many laboratories use the pPAX8 antibody, a clear understanding of the
      differential staining patterns is necessary. The differential diagnosis of a B
      cell lymphoma should be entertained when a pPAX8-positive, epithelial marker
      negative neoplasm of uncertain primary origin is encountered.

PMID- 23163629
TI  - Posterior muscolofascial reconstruction incorporated into urethrovescical
      anastomosis during robot-assisted radical prostatectomy.
AB  - The rationale of posterior musculofascial plate reconstruction during radical
      prostatectomy is to shorten the time to reach urinary continence recovery and to
      reduce the risk of bleeding and anastomosis leakage. We describe our original
      technique incorporating the posterior muscolofascial reconstruction into
      urethrovesical anastomosis using robot-assisted radical prostatectomy (RARP). For
      this reconstructive step, we use a 30-cm V-Loc 90 3-0 barbed suture (V-20 tapered
      needle). Specifically, the free edge of the posterior layer of the Denonvilliers
      fascia is approximated to the posterior part of the sphincteric apparatus in a
      running fashion from left to right. The musculature of the urethral wall is
      incorporated in this first layer of the running suture. This suture is then
      continued back to the left in a second layer incorporating the anterior layer of
      the Denonvilliers fascia (or prostatovesical muscle), the bladder neck, and again
      the urethra, this time also with urethral mucosa. The urethrovesical anastomosis
      is completed using a second running barbed suture (15-cm V-Loc 90 3-0 barbed
      suture, V-20 tapered needle). No intraoperative complications were observed
      during this step of the procedure. Anastomotic leakages were observed only in 2%
      of cases. Only 12.5% showed urinary incontinence after catheter removal (1-2
      pads). At mean follow-up of 9 months, the urinary continence recovery was 95%,
      and an anastomosis stricture necessitating an endoscopic incision developed in
      only three (1.5%) patients. Recent systematic reviews of the literature showed
      only a minimal advantage in favor of posterior musculofascial reconstruction in
      terms of urinary continence recovery within 1 month after radical prostatectomy.
      We support the use of this step of RARP because it is simple, reproducible, with
      a very limited increase in operative time, and with only a slight risk of
      potential harm to the patient. Moreover, it could improve hemostasis and provide
      greater support for a delicate anastomosis.

PMID- 23163630
TI  - Newborn screening for cystic fibrosis in Serbia: a pilot study.
AB  - BACKGROUND: We performed a pilot study of neonatal screening for cystic fibrosis
      (CF) in order to introduce it to the national screening program in Serbia.
      METHODS: Immunoreactive trypsinogen (IRT) concentrations were analyzed in dried
      blood spot samples. Patients were recalled for repeated measurements in case of
      high IRT levels. Persisting high IRT levels resulted in DNA testing for the 29
      most common mutations in the CF transmembrane regulator (CFTR) gene (IRT/IRT/DNA
      method). Sweat chloride measurements and clinical assessment were further
      performed for newly diagnosed patients. RESULTS: Of 1000 samples, three were
      initially positive and were further analyzed for the presence of the most common
      CFTR mutations in the Serbian population. DNA analysis revealed two patients
      being homozygous for F508del mutation. One sample was false positive, as the
      genetic test proved to be negative and associated with normal sweat chloride
      concentration and unremarkable clinical presentation. CONCLUSIONS: The results of
      our pilot study justified the expanding of the routine neonatal screening program
      in Serbia with CF. Data could be used in future in order to obtain accurate
      incidence of CF and carrier prevalence in our country.

PMID- 23163631
TI  - Variation in hospital antibiotic prescribing practices for children with acute
      lymphoblastic leukemia.
AB  - Antibiotic variation among pediatric oncology patients has not been well
      described. Identification of significant variability in antibiotic use within
      this population would warrant evaluation of its clinical impact. We conducted a
      retrospective cohort study of newly diagnosed patients with pediatric acute
      lymophoblastic leukemia (ALL) hospitalized from 1999 to 2009 in 39 freestanding
      US children's hospitals within the Pediatric Health Information System.
      Medication use data were obtained for the first 30 days from each patient's index
      ALL admission date. Antibiotic exposure rates were reported as antibiotic
      days/1000 hospital days. Unadjusted composite broad-spectrum antibiotic exposure
      rates varied from 577 to 1628 antibiotic days/1000 hospital days. This wide range
      of antibiotic exposure was unaffected by adjustment for age, gender, race and
      days of severe illness (adjusted range: 532-1635 days of antibiotic therapy/1000
      hospital days). Antibiotic use for children with newly diagnosed ALL varies
      widely across children's hospitals and is not explained by demographics or
      illness severity.

PMID- 23163633
TI  - Response of soil microorganisms to As-produced and functionalized single-wall
      carbon nanotubes (SWNTs).
AB  - The use of single-wall carbon nanotubes (SWNTs) in manufacturing and biomedical
      applications is increasing at a rapid rate; however data on the effects of a
      potential environmental release of the materials remain sparse. In this study,
      soils with either low or high organic matter contents as well as pure cultures of
      E. coli are challenged with either raw as-produced SWNTs (AP-SWNTs) or SWNTs
      functionalized with either polyethyleneglycol (PEG-SWNTs) or m-polyaminobenzene
      sulfonic acid (PABS-SWNTs). To mimic chronic exposure, the soil systems were
      challenged weekly for six weeks; microbial activities and community structures
      for both the prokaryote and eukaryote community were evaluated. Results show that
      repeated applications of AP-SWNTs can affect microbial community structures and
      induce minor changes in soil metabolic activity in the low organic matter
      systems. Toxicity of the three types of SWNTs was also assessed in liquid
      cultures using a bioluminescent E. coli-O157:H7 strain. Although decreases in
      light were detected in all treated samples, low light recovery following glucose
      addition in AP-SWNTs treatment and light absorption property of SWNTs particles
      suggest that AP-SWNTs suppressed metabolic activity of the E. coli, whereas the
      two functionalized SWNTs are less toxic. The metals released from the raw forms
      of SWNTs would not play a role in the effects seen in soil or the pure culture.
      We suggest that sorption to soil organic matter plays a controlling role in the
      soil microbiological responses to these nanomaterials.

PMID- 23163632
TI  - Molecular electronic tuning of photosensitizers to enhance photodynamic therapy:
      synthetic dicyanobacteriochlorins as a case study.
AB  - Photophysical, photostability, electrochemical and molecular-orbital
      characteristics are analyzed for a set of stable dicyanobacteriochlorins that are
      promising photosensitizers for photodynamic therapy (PDT). The bacteriochlorins
      are the parent compound (BC), dicyano derivative (NC)2BC and corresponding zinc
      (NC)2BC-Zn and palladium chelate (NC)2BC-Pd. The order of PDT activity against
      HeLa human cancer cells in vitro is (NC)2BC-Pd > (NC)2BC > (NC)2BC-Zn ~ BC. The
      near-infrared absorption feature of each dicyanobacteriochlorin is
      bathochromically shifted 35-50 nm (748-763 nm) from that for BC (713 nm).
      Intersystem crossing to the PDT-active triplet excited state is essentially
      quantitative for (NC)2BC-Pd. Phosphorescence from (NC)2BC-Pd occurs at 1122 nm
      (1.1 eV). This value and the measured ground-state redox potentials fix the
      triplet excited-state redox properties, which underpin PDT activity via Type-1
      (electron transfer) pathways. A perhaps counterintuitive (but readily explicable)
      result is that of the three dicyanobacteriochlorins, the photosensitizer with the
      shortest triplet lifetime (7 MUs), (NC)2BC-Pd has the highest activity.
      Photostabilities of the dicyanobacteriochlorins and other bacteriochlorins
      studied recently are investigated and discussed in terms of four phenomena:
      aggregation, reduction, oxidation and chemical reaction. Collectively, the
      results and analysis provide fundamental insights concerning the molecular design
      of PDT agents.

PMID- 23163634
TI  - Dense electron system from gate-controlled surface metal-insulator transition.
AB  - Two-dimensional electron systems offer enormous opportunities for science
      discoveries and technological innovations. Here we report a dense electron system
      on the surface of single-crystal vanadium dioxide nanobeam via electrolyte
      gating. The overall conductance of the nanobeam increases by nearly 100 times at
      a gate voltage of 3 V. A series of experiments were carried out which rule out
      electrochemical reaction, impurity doping, and oxygen vacancy diffusion as the
      dominant mechanism for the conductance modulation. A surface insulator-to-metal
      transition is electrostatically triggered, thereby collapsing the bandgap and
      unleashing an extremely high density of free electrons from the original valence
      band within a depth self-limited by the energetics of the system. The dense
      surface electron system can be reversibly tuned by the gating electric field,
      which provides direct evidence of the electron correlation driving mechanism of
      the phase transition in VO(2). It also offers a new material platform for
      implementing Mott transistor and novel sensors and investigating low-dimensional
      correlated electron behavior.

PMID- 23163637
TI  - Associations between parental psychological control and relational aggression in
      children and adolescents: a multilevel and sequential meta-analysis.
AB  - Youth aggression has been associated with negative parenting practices, but
      previous research about this association has mainly focused on physical and
      verbal aggression. Because more subtle forms of aggression are considered at
      least as harmful as their physical and verbal counterparts, there is a growing
      scientific interest in parenting practices that are linked with relational
      aggression. Guided by social learning theory, a link between youth relational
      aggression and parental psychological control has been postulated, but the
      empirical evidence is inconsistent. The present meta-analysis provides a
      multilevel and sequential quantitative synthesis of 165 dependent effect sizes
      (23 studies) encompassing 8,958 youths. Across studies, a positive, albeit weak,
      association between parental psychological control and relational aggression was
      found. The sequential analysis demonstrated that sufficient cumulative knowledge
      was attained to yield convincing evidence on this overall association. Moderator
      analyses revealed that developmental period and assessment method were associated
      with differences in research findings. Overall, however, results suggest that
      clarifying the precise role of psychological control in the development and
      maintenance of relational aggression requires more targeted primary research,
      which in turn would allow additional and more complex synthesis efforts with
      potentially more nuanced conclusions.

PMID- 23163638
TI  - A bias for the natural? Children's beliefs about traits acquired through effort,
      bribes, or medicine.
AB  - Three studies compared beliefs about natural and late blooming positive traits
      with those acquired through personal effort, extrinsic rewards or medicine. Young
      children (5-6 years), older children (8-13 years), and adults all showed a strong
      bias for natural and late blooming traits over acquired traits. All age groups,
      except 8- to 10-year-olds, treated natural and late-blooming traits as fixed
      essences that would persist over time and under challenging conditions. Older
      children and adults viewed traits acquired by intrinsic effort as more similar to
      natural and late-blooming traits than those acquired through bribes or medicine,
      suggesting that intrinsic effort itself comes to be seen as a more natural
      mechanism of change. A bias for the natural may therefore be an early emerging
      way of evaluating others that is reinforced by the ambient culture and becomes
      stronger with increasing age.

PMID- 23163639
TI  - Modified coat protein forms the flexible spindle-shaped virion of haloarchaeal
      virus His1.
AB  - Extremophiles are found in all three domains of cellular life. However,
      hyperthermic and hypersaline environments are typically dominated by archaeal
      cells which also hold the records for the highest growth temperature and are able
      to grow even at saturated salinity. Hypersaline environments are rich of virus
      like particles, and spindle-shaped virions resembling lemons are one of the most
      abundant virus morphotypes. Spindle-shaped viruses are archaea-specific as all
      the about 15 such virus isolates infect either hyperthermophilic or halophilic
      archaea. In the present work, we studied spindle-shaped virus His1 infecting an
      extremely halophilic euryarchaeon, Haloarcula hispanica. We demonstrate that His1
      tolerates a variety of salinities, even lower than that of seawater. The detailed
      analysis of the structural constituents showed that the His1 virion is composed
      of only one major and a few minor structural proteins. There is no lipid bilayer
      in the His1 virion but the major structural protein VP21 is most likely lipid
      modified. VP21 forms the virion capsid, and the lipid modification probably
      enables hydrophobic interactions leading to the flexible nature of the virion.
      Furthermore, we propose that euryarchaeal virus His1 may be related to
      crenarchaeal fuselloviruses, and that the short-tailed spindle-shaped viruses
      could form a structure-based viral lineage.

PMID- 23163640
TI  - Ozone photodissociation: isotopic and electronic branching ratios for symmetric
      and asymmetric isotopologues.
AB  - We present new calculations of the branching ratios between the various
      electronic and isotopic photodissociation channels of ozone. Special emphasis is
      placed on the isotopic/isotopologue differences because the contribution of the
      ozone photodissociation to the oxygen isotope and ozone isotopologue enrichments
      or fractionations is important for atmospheric applications. These branching
      ratios, which depend on photon energy, have been calculated with a full quantum
      mechanical wavepacket propagation approach: the multiconfiguration time-dependent
      Hartree (MCTDH) method. Five ozone isotopologues are considered: three symmetric,
      (16)O(3) (noted 666), (16)O(17)O(16)O (676), and (16)O(18)O(16)O (686); two
      asymmetric, (16)O(2)(17)O (noted 667) and (16)O(2)(18)O (668). The 668 and 667
      asymmetric isotopologues can dissociate into either 66 + 8 or 68 + 6 for 668 and
      into 66 + 7 or 67 + 6 for 667. In the ranges of the Chappuis and Hartley bands,
      the dissociation is very fast and electronic and isotopic branching ratios are
      obtained from the wavepacket fluxes through complex absorbing potentials (CAPs)
      located perpendicular to the dissociation channels of the potential energy
      surfaces (PESs) of the A (1)B(1) (Chappuis) and B 3(1)A' (Hartley/Huggins)
      electronic states. In the range of the Huggins band the dissociation is much
      slower and the isotopic branching ratios of 667 and 668 asymmetric isotopologues,
      (e.g; 668 -> 66 + 8 or 86 + 6) are obtained from the ratios of two partial
      absorption cross sections corresponding to the selective excitation of one or the
      other of the two isomers of C(s) symmetry, which dissociate respectively into 66
      + 8 and 86 + 6. We find that the photodissociation of the 668 asymmetric
      isotopologue favors the 68 + 6 channel with a propensity varying between 52%
      (Hartley) and 54% (Huggins) as a function of the photon energy. The electronic
      branching ratios to the singlet channel (O(3) + hupsilon -> O((1)D) +
      O(2)((1)Delta)) are all close to 90% above ~32,000 cm(-1). Below this energy, the
      singlet channel is energetically closed and only the triplet channel (O(3) +
      hupsilon -> O((3)P) + O(2)((3)Sigma)) is open. These branching ratios are
      required to calculate the photolysis rates of each ozone isotopologue, which in
      turn contribute to the atomic oxygen and the ozone isotopic enrichments in the
      atmosphere.

PMID- 23163641
TI  - Assembly and post-modification of a metal-organic nanotube for highly efficient
      catalysis.
AB  - A metal-organic nanotube (MONT) was synthesized by linking up the bent organic
      ligands and the tetra-coordinated zinc cations under mild conditions. Structural
      analysis revealed that the MONT has a very large exterior wall diameter of 4.91
      nm and an interior channel diameter of 3.32 nm. Interlocking of the nanotubes
      gives rise to a 3D chiral framework containing 1D helical cylindered channels
      with diameter of 2.0 nm. The MONT has very interesting property by synergizing
      the functionality of nanotubes, metal-organic frameworks (MOFs), and N
      heterocyclic carbenes (NHCs). The dye adsorption experiments demonstrate that the
      channels of the MONTs are accessible to large reagents typically used for
      catalysis. The postmodification of the MONT can be easily operated by unmarking
      the imidazolium moieties in the channel walls, which was conducted as a highly
      active heterogeneous catalyst for Suzuki-Miyaura and Heck coupling reactions,
      hydrogenation of olefins and nitrobenzene, while the constituent elements are
      less efficient for these reactions under the same conditions.

PMID- 23163642
TI  - Spectrum of Fuchs uveitic syndrome in a North Indian population.
AB  - PURPOSE: To describe patients with Fuchs uveitis syndrome (FUS) in North India.
      DESIGN: Retrospective case series. METHODS: One hundred ninety-eight eyes of 183
      patients with FUS were reviewed at the Post Graduate Institute of Medical
      Education and Research, Advanced Eye Centre, Department of Ophthalmology, between
      December 1996 and September 2011. Demographic profile, clinical findings at
      presentation, risk of new complications, and rate of decreased vision were the
      main outcome measures. RESULTS: The mean age at presentation was 30.1 +/- 9.4
      years. Male-to-female ratio was 1.1:1. Fifteen patients (8.1%) had bilateral
      involvement. Clinical findings at presentation included diffuse keratic
      precipitates (92.4%), anterior chamber cells (54.5%), diffuse iris atrophy
      without hypochromia (29.3%), heterochromia (24.7%), iris nodules (16.1%),
      cataract/pseudophakia (79.3%), vitreous cells (61.1%), elevated intraocular
      pressure (13.6%), and chorioretinal scars (2%). On fluorescein angiography,
      hyperfluorescence of the optic disc was detected in 28 of 51 eyes (55%),
      peripheral vasculitis in 1 (2%) and both in 8 eyes (15.7%). OCT showed traction
      papillopathy in 6 of 34 eyes (17.6%). None of the eyes showed cystoid macular
      edema. CONCLUSION: Heterochromia is seen only in 25% of patients with
      Fuchsheterochromic uveitis in brown irides. Diffuse stellate keratic
      precipitates, low cellular reaction, vitritis, vitreous opacities, diffuse iris
      stromal atrophy in the absence of posterior synechia, and macular edema are other
      parameters helpful in diagnosing FUS.

PMID- 23163643
TI  - Label-free strategy for in-situ analysis of protein binding interaction based on
      attenuated total reflection surface enhanced infrared absorption spectroscopy
      (ATR-SEIRAS).
AB  - A versatile ATR-SEIRAS methodology is described herein for highly sensitive
      analysis of immunoglobulin (IgG) recognition. This strategy allows in situ
      tracking of specific protein binding at the liquid-solid interface. Most
      importantly, interferential signal from environmental molecules (e.g., water,
      nonspecific binding molecules, and bulk molecules) can be eliminated to
      negligible levels by using the ATR analysis mode, and the sensitive IR structural
      information of target proteins is obtained simultaneously. A simplified numerical
      model has been established to quantitatively describe the kinetics and
      thermodynamics of protein recognition processes at surfaces. Compared with
      conventional label-free methods for protein binding study, experimental results
      obtained from IR spectroscopic information are more reliable. The presented ATR
      SEIRAS method is powerful in studying surface limited protein binding reactions.

PMID- 23163644
TI  - Continuous direct tablet compression: effects of impeller rotation rate, total
      feed rate and drug content on the tablet properties and drug release.
AB  - CONTEXT: Continuous processing is becoming popular in the pharmaceutical industry
      for its cost and quality advantages. OBJECTIVE: This study evaluated the
      mechanical properties, uniformity of dosage units and drug release from the
      tablets prepared by continuous direct compression process. MATERIALS AND METHODS:
      The tablet formulations consisted of acetaminophen (3-30% (w/w)) pre-blended with
      0.25% (w/w) colloidal silicon dioxide, microcrystalline cellulose (69-96% (w/w))
      and magnesium stearate (1% (w/w)). The continuous tableting line consisted of
      three loss-in-weight feeders and a convective continuous mixer and a rotary
      tablet press. The process continued for 8 min and steady state was reached within
      5 min. The effects of acetaminophen content, impeller rotation rate (39-254 rpm)
      and total feed rate (15 and 20 kg/h) on tablet properties were examined. RESULTS
      AND DISCUSSION: All the tablets complied with the friability requirements of
      European Pharmacopoeia and rapidly released acetaminophen. However, the relative
      standard deviation of acetaminophen content (10% (w/w)) increased with an
      increase in impeller rotation rate at a constant total feed rate (20 kg/h). A
      compression force of 12 kN tended to result in greater tablet hardness and
      subsequently a slower initial acetaminophen release from tablets when compared
      with those made with the compression force of about 8 kN. CONCLUSIONS: In
      conclusion, tablets could be successfully prepared by a continuous direct
      compression process and process conditions affected to some extent tablet
      properties.

PMID- 23163645
TI  - Primary lymphoma arising in a mature cystic teratoma of the ovary.

PMID- 23163646
TI  - HTLV-1-associated infective dermatitis: updates on the pathogenesis.
AB  - HTLV-1-associated infective dermatitis (HAID) is the main paediatric
      manifestation of human T-cell lymphotropic virus type 1 (HTLV-1). It is
      characterised by a chronic exudative eczematous eruption and persistent infection
      with Staphylococcus aureus (SA) and beta-haemolytic streptococci (BHS).
      Prevalence is highest in the Caribbean and Brazil; however, cases have been
      reported in other HTLV-1 endemic regions. Approximately 20 million people
      worldwide are infected with HTLV-1 and only 5-10% suffer from disease. Other
      manifestations include adult T-cell leukaemia/lymphoma (ATLL) and tropical
      spastic paraparesis/HTLV-1-associated myelopathy (TSP/HAM). HAID may also
      progress to ATLL or TSP/HAM. Treatment options are limited to prolonged
      antibiotic therapy. The aim of this paper is to review existing evidence and
      propose new theories on the pathogenesis of HAID. The current view is that HTLV-1
      infection is required and in susceptible individuals leads to immune
      dysregulation with subsequent immunosuppression and superinfection with SA and
      BHS. Evidence suggests that host, environment and genetic factors may play a
      causative role. Genetic factors within ethnic groups determine host immune
      response and carrier state or disease manifestation of HTLV-1 infection.
      Increased IgE levels may contribute to the SA and BHS superinfection in HAID.
      Additionally, the possible impact of filaggrin, skin proteinase dysregulation,
      Langerhans cell dysfunction and TH2 chemokines is highlighted. More than 45 years
      since the discovery of HAID, the exact pathogenesis is still not fully
      understood. Further research is still needed to clearly elucidate the exact
      pathogenic mechanism of HAID.

PMID- 23163647
TI  - Unravelling hair follicle-adipocyte communication.
AB  - Here, we explore the established and potential roles for intradermal adipose
      tissue in communication with hair follicle biology. The hair follicle delves deep
      into the rich dermal macroenvironment as it grows to maturity where it is
      surrounded by large lipid-filled adipocytes. Intradermal adipocytes regenerate
      with faster kinetics than other adipose tissue depots and in parallel with the
      hair cycle, suggesting an interplay exists between hair follicle cells and
      adipocytes. While adipocytes have well-established roles in metabolism and energy
      storage, until recently, they were overlooked as niche cells that provide
      important growth signals to neighbouring skin cells. We discuss recent data
      supporting adipocytes as niche cells for the skin and skin pathologies that may
      be related to alterations in skin adipose tissue defects.

PMID- 23163648
TI  - Characterization and longitudinal monitoring of melanoma growth in ret-transgenic
      mice using a single-sequence MRI protocol.
AB  - Spontaneous melanoma models in transgenic mice are increasingly used in
      preclinical research as they most closely match the progression of melanoma in
      humans. While optical inspection only allows analysis of tumors located on the
      skin, the accurate measurement and growth of subcutaneous tumors have not been
      adequately assessed. To improve the measurement accuracy of melanoma tumors, we
      used a fast single-sequence MRI protocol at 9.4 Tesla for longitudinal
      characterization of a ret-transgenic mouse model. Repeated MRI (average
      acquisition time 30 min per animal) of the trunk (excluding head and distal
      limbs) in six siblings revealed an increase in the mean total tumor volume (TTV)
      from 102.0 +/- 80.5 mm(3) at 35 days of age to 434.8 +/- 154.9 mm(3) by 77 days.
      The main tumor load was located within the pelvis (>40%), followed by the
      proximal hind limbs and groins (>30%). The smallest detectable tumor measured
      0.07 mm(3). Inter-rater reliability between a radiologist and a veterinarian
      analysing MRI data was 0.993 for TTV and 0.840 for number of tumors (both p <
      0.001). We thus conclude that because of the high variance of TTV of same-aged
      mice, MRI should be used (i) to establish treatment groups matched for TTV and
      (ii) for longitudinal examination of the TTV in mice over the course of
      treatments.

PMID- 23163649
TI  - Establishing an allergic eczema model employing recombinant house dust mite
      allergens Der p 1 and Der p 2 in BALB/c mice.
AB  - The major house dust mite allergens Der p 1 and Der p 2 are prevalent inducers of
      eczema. Der p 1 is a cysteine protease disrupting epithelial barriers, whereas
      Der p 2 functionally mimics the LPS-binding compound MD-2 within the TLR4
      complex. In this work, we tested the percutaneous sensitizing capacity of
      recombinant (r) Der p 1 and Der p 2 in BALB/c mice. Mice were sensitized by
      percutaneous application of low (10 MUg/application) and high dose (100 MUg) rDer
      p 1 or rDer p 2, or with rDer p 1 followed by rDer p 2. Allergen-specific and
      total IgE antibodies were determined by ELISA. Eczema of BALB/c was classified by
      the itching score and corresponded to erosions. Infiltrating immune cells were
      identified by haematoxylin/eosin and Giemsa staining for eosinophils or mast
      cells, CD3 staining for T lymphocytes. Percutaneous treatments with rDer p 1, but
      not rDer p 2-induced specific IgG1. However, cotreatment with rDer p 1 led to
      increase in anti-Der p 2 IgG titres. Both allergens elicited skin erosions
      because of scratching, thickening of the epidermis, and eosinophil and T-cell
      infiltration. Our data indicate that recombinant mite allergens in the absence of
      adjuvant are sufficient for inducing eczema in BALB/c mice. As the enzymatic
      activity of an allergen might be an important cofactor for specific sensitization
      via the skin, Der p 1 may act as adjuvant for other allergens too. The presented
      mouse model is suitable for investigating the mechanisms of allergic eczema.

PMID- 23163650
TI  - Protein kinase A activation inhibits oncogenic Sonic hedgehog signalling and
      suppresses basal cell carcinoma of the skin.
AB  - Basal cell carcinoma of the skin (BCC) is caused by constitutive activation of
      the Sonic hedgehog (Shh) pathway, mainly through mutations either in the Shh
      receptor Patched (PTCH) or in its co-receptor Smoothened (Smo). Inhibitors of
      this pathway that are currently in clinical trials inhibit Smo. However,
      mutations in Smo can result in resistance to these inhibitors. To target most
      BCCs and avoid acquired resistance because of Smo mutations, inhibiting the Shh
      pathway downstream of Smo is critical. Attractive downstream targets would be at
      the level of Gli proteins, the transcriptional activators of this pathway in
      BCCs. Previously it has been shown that Gli1 and Gli2, when phosphorylated by
      protein kinase A (PKA), are targeted for proteosomal degradation. Here we show
      that PKA activation via the cAMP agonist forskolin is sufficient to completely
      abolish oncogenic Smo activity in vitro. In an inducible BCC mouse model due to a
      Smo mutation that confers resistance to current Smo inhibitors, topical forskolin
      treatment significantly reduced Gli1 mRNA levels and resulted in strongly
      suppressed BCC tumor growth. Our data show that forskolin inhibits the growth of
      even those BCCs that are resistant to Smo inhibitors and provide a proof-of
      principle framework for the development of topically applied human skin-permeable
      novel pharmacologic inhibitors of oncogenic Shh-signaling through PKA activation.

PMID- 23163651
TI  - Altered levels of LXR-alpha: crucial implications in the pathogenesis of
      vitiligo.
AB  - In recent times, the role of LXRs in skin physiology and pathology has evolved
      rapidly because of their role in proliferation, carcinogenesis, differentiation
      and permeability barrier function. LXRs were identified as promising drug targets
      for the treatment of many skin diseases. For this study, skin biopsies were taken
      from 15 patients with vitiligo and six controls to culture melanocytes from
      clinically active perilesional and normal skin. Gene expression was examined by
      reverse transcriptase-polymerase chain reaction analysis. Role of LXR-alpha in
      regulating the expression of MMPs was checked by gene knock-down, and its role in
      vitiligo pathogenesis was checked by treatment with LXR-alpha agonist 22(R)
      hydroxycholesterol. After treatment adhesion assay, annexin V staining and
      proliferation assay were performed. The expression of LXR-alpha was relatively
      more in perilesional skin melanocytes as compared to uninvolved skin melanocytes
      of non-segmental vitiligo patient, and controls on the other hand, perilesional
      melanocytes were more prone to apoptosis. LXR-alpha gene knock-down significantly
      increases the expression of MMPs. LXR-alpha agonist 22(R)-hydroxycholesterol
      treatment significantly decreases melanocyte adhesion, apoptosis and
      proliferation. Higher expression of LXR-alpha in perilesional skin melanocytes
      significantly decreases the adhesion, proliferation and matrix metalloproteinases
      and increases apoptosis.

PMID- 23163652
TI  - GATA-3 regulates differentiation-specific loricrin gene expression in
      keratinocytes.
AB  - Loricrin is a major component of the epidermal cornified cell envelope and is
      expressed only in terminally differentiated keratinocytes. This cell
      differentiation-specific expression pattern suggests specific regulatory
      mechanisms for activation of loricrin gene transcription in differentiated
      keratinocytes. Here, we identified a positive regulatory element in the proximal
      promoter region of the loricrin gene involved in activation of its expression in
      differentiated keratinocytes. A database search indicated that this sequence
      contained a GATA-3 binding motif. Constructs with point mutations in the GATA-3
      binding motif showed decreased reporter activity, indicating that GATA-3
      positively regulates loricrin gene transcription. Western blotting analysis
      indicated that GATA-3 is more abundant in differentiated than in undifferentiated
      keratinocytes. Cotransfection experiments indicated that GATA-3 activates
      transcription of the loricrin gene in a cooperative manner with c-Fos and Sp1.
      These findings indicate that GATA-3 contributes to keratinocyte differentiation
      specific activation of loricrin gene transcription via interaction with c-Fos and
      Sp1.

PMID- 23163653
TI  - Nature versus nurture: does human skin maintain its stratum corneum lipid
      properties in vitro?
AB  - Human skin equivalents (HSEs) mimic human skin closely, but show differences in
      their stratum corneum (SC) lipid properties. The aim of this study was to
      determine whether isolation of primary cells, which is needed to generate HSEs,
      influence the SC lipid properties of HSEs. For this purpose, we expanded explants
      of intact full thickness human skin and isolated epidermal sheets in vitro. We
      investigated whether their outgrowths maintain barrier properties of human skin.
      The results reveal that the outgrowths and human skin have a similar morphology
      and expression of several differentiation markers, except for an increased
      expression of keratin 16 and involucrin. The outgrowths show a decreased SC fatty
      acid content compared with human skin. Additionally, SC lipids of the outgrowths
      have a predominantly hexagonal packing, whereas human skin has the dense
      orthorhombic packing. Furthermore, the outgrowths have lipid lamellae with a
      slightly reduced periodicity compared with human skin. These results demonstrate
      that the outgrowths do not maintain all properties observed in human skin,
      indicating that changes in properties of HSEs are not caused by isolation of
      primary cells, but by culture conditions.

PMID- 23163654
TI  - Epidermal morphogenesis during progressive in vitro 3D reconstruction at the air
      liquid interface.
AB  - Keratinocyte monolayers, cultured in immersed conditions, constitute a frequently
      used in vitro model system to study keratinocytes behaviour in response to
      environmental assaults. However, monolayers lack the keratinocyte terminal
      differentiation and the organization of the epidermal tissue, which are observed
      in vivo. Advancements of in vitro techniques were used to reconstruct three
      dimensional equivalents that mimic human epidermis in terms of layering,
      differentiation and barrier function. Here, we update a published method and
      illustrate the progressive morphogenesis responsible for in vitro reconstruction.
      The analysis of cell proliferation, expression of differentiation markers and
      barrier efficacy demonstrate the excellent similarity of the reconstructed tissue
      with normal human epidermis. Availability of epidermal tissue during its
      reconstruction phase in culture appears crucial for studies intending to
      challenge the barrier function.

PMID- 23163655
TI  - Lack of microRNA miR-150 reduces the capacity of epidermal Langerhans cell cross
      presentation.
AB  - MicroRNAs (miRNAs) are evolutionarily conserved small non-coding RNAs that
      repress target genes at post-transcriptional level. Langerhans cells (LCs) are
      skin-residential dendritic cells (DCs) with a life cycle distinct from other
      types of DCs. miRNA deficiency interrupts the homoeostasis and function of
      epidermal LCs, suggesting the critical roles of miRNAs in LC development and
      function. However, the roles of individual miRNAs in regulating LC development
      and function remain completely unknown. MiRNA miR-150 is highly expressed in
      mature lymphocytes and regulates T- and B-cell development and function. Here, we
      reported that miR-150 is also expressed in epidermal LCs, and its expression is
      significantly down-regulated during in vitro LC maturation. Using a miR-150
      knockout mouse model, we found that lack of miR-150 reduces the capacity of LCs
      to cross-present a soluble antigen to antigen-specific CD8(+) T cells, but does
      not disturb the development, maturation, migration and phagocytic capacity of
      LCs. Thus, our data indicate that miR-150 is required for LC cross-presentation.

PMID- 23163656
TI  - Testosterone exerts selective anti-inflammatory effects on human skin mast cells
      in a cell subset dependent manner.
AB  - Androgens are known to exert anti-inflammatory effects but their impact on mast
      cells (MCs) remains to be determined. Here, we show that MCs isolated from human
      foreskin samples (male) and those from breast skin (female) express the androgen
      receptor, albeit with a 10-fold difference between the subsets. While fundamental
      MC properties (FcepsilonRI, c-Kit, tryptase; histamine release upon FcepsilonRI
      cross-linking) were unaffected or slightly reduced (chymase) by testosterone, the
      hormone had a more profound impact on the production of cytokines, with IL-6
      being a target (reduction by 53%). Interestingly, this effect was limited to
      breast skin MCs (15 of 16 donors displayed this phenomenon), but was not
      reproduced by foreskin MCs. Collectively, effector functions of human skin MCs
      are modulated by androgens in a gene-selective and MC subset-specific fashion.
      Possibly, MCs from women are more susceptible to testosterone. We also
      demonstrate that MC IL-6 production is highly variable among individuals.

PMID- 23163657
TI  - Expression and localization of Artemis serine 516 phosphorylation in human scalp
      skin.
AB  - Artemis phosphorylation at serine 516 (Ser516) has important regulatory functions
      in the repair of radiation-induced DNA damage, V(D)J recombination, p53-dependent
      apoptosis and cell cycle control. Accordingly, Artemis mutations can lead to
      Omenn syndrome, which is associated with human radiosensitive severe combined
      immunodeficiency syndrome and alopecia. In this study, we investigated the
      expression of Ser516 phosphorylation of Artemis in the epidermis and epidermal
      appendages in normal human scalp skin. Immunofluorescence analysis revealed
      Ser516 phosphorylation of Artemis in the upper and middle portion of anagen hair
      follicle [including outer root sheath (ORS), inner root sheath but not stratum
      basale], hair matrix, sebaceous glands (secretory and ductal portions), eccrine
      sweat glands (secretory and ductal portions) and epidermis (stratum basale and
      stratum granulosum), respectively. Artemis phosphorylation at Ser516 was most
      prominent in ORS keratinocytes. Therefore, we suggest that phosphorylation of
      Artemis at Ser516 could be involved in regulation of human epidermal appendages.

PMID- 23163658
TI  - Expressions and inhibitory functions of CD300a receptors on purified human
      basophils.
AB  - The inhibitory myeloid immunoglobulin receptor CD300a (IRp60) has been shown to
      downregulate mast cell and eosinophil activities, thereby serving as a potential
      target for inhibiting allergic effector cell input in allergy. Our aims were to
      study the expression and functional properties of this receptor in purified human
      basophils, cells that crucially contribute to Th2-type immunity and allergy.
      Basophils homogeneously expressed CD300a as well as the inhibitory receptor
      CD200R on their cell surface, and these expressions increased after anti-IgE
      stimulation. IgE-mediated basophil degranulation was also significantly inhibited
      by crosslinking of either CD200R or CD300a (by 90% and 50%, respectively).
      Inhibitory SHIP-1 phosphorylations were also induced by CD200R and CD300a,
      although they were not noticeably increased by IgE-dependent activation. We
      conclude that both CD200R and CD300a play a role in reducing IgE-mediated
      basophil function and may crucially govern the known differential activities of
      these cells in vivo.

PMID- 23163659
TI  - In vitro formation of organized structure between keratinocytes and dorsal-root
      ganglion cells.
AB  - We recently found that the morphology in a co-culture system of keratinocytes and
      dorsal-root ganglion-derived cells depended on the timing of seeding of the two
      cell types. In skin, epidermis is formed first, followed by construction of
      peripheral nerve structure. Therefore, we hypothesized that formation of
      peripheral nerve structure in the epidermis might be driven by interaction
      between keratinocytes and nerve cells. In the present study, we tested this idea
      by incubating keratinocytes and dorsal-root ganglion cells in a spatially
      separated manner and observing the morphological changes in the co-culture
      system. Extension of nerve fibre-like structures from the ganglion cells was
      observed, and within 3 days after seeding, many nerve fibre-like extensions
      penetrated into the keratinocyte cluster, subsequently forming a network that
      appeared to resemble the cutaneous peripheral nervous system. Our present model
      may be useful for studying the formation of peripheral nerve structure in the
      skin.

PMID- 23163660
TI  - Cystatin M/E knockdown by lentiviral delivery of shRNA impairs epidermal
      morphogenesis of human skin equivalents.
AB  - The protease inhibitor cystatin M/E (CST6) regulates a biochemical pathway
      involved in stratum corneum homeostasis, and its deficiency in mice causes
      ichthyosis and neonatal lethality. Cystatin M/E deficiency has not been described
      in humans so far, and we did not detect disease-causing mutations in the CST6
      gene in a large number of patients with autosomal recessive congenital
      ichthyosis, who were negative for mutations in known ichthyosis-associated genes.
      To investigate the phenotype of CST6 deficiency in human epidermis, we used
      lentiviral delivery of short hairpin RNAs that target CST6 in a 3D reconstructed
      skin model. Surprisingly, CST6 deficiency did not cause an ichthyosis-like
      phenotype, but prevented the development of a multilayered epidermis. From this
      study, we conclude that CST6 deficiency may be incompatible with normal human
      foetal development.

PMID- 23163661
TI  - IL-33 is secreted by psoriatic keratinocytes and induces pro-inflammatory
      cytokines via keratinocyte and mast cell activation.
AB  - IL-33 is a novel pro-inflammatory cytokine and ligand for the orphan receptor
      ST2. Although originally defined as an inducer of Th2-mediated responses, IL-33
      was recently found to be involved in arthritis, a Th1/Th17-mediated disease.
      Here, we assessed the ability of IL-33 to promote inflammation via mast cells
      (MCs) and keratinocytes (KCs) activation in psoriasis. IL-33 resulted elevated in
      the skin but not in the serum of psoriasis patients. IL-33 was secreted by
      psoriasis KCs and HaCaT cells after TNF-alpha stimulation. In HMC-1, TNF-alpha,
      but not IL-17, could induce a robust increase in IL-33 expression. In HaCaT
      cells, TNF-alpha was able to induce IL-6, MCP-1 and VEGF, and the addition of IL
      33 reinforced these increases. TNF-alpha + IL-33 combination showed similar
      results in primary KCs and ex vivo skin organ culture. In conclusion, our study
      suggests that IL-33 may be involved in psoriasis biology via MCs and KCs.

PMID- 23163662
TI  - Characterization of fruity aroma modifications in red wines during malolactic
      fermentation.
AB  - The role of malolactic fermentation (MLF) in the fruity aroma of red wines was
      investigated by an analytical study on more than 60 volatile compounds in 48 red
      wines made in varied conditions and supplemented by a sensory study. Lactic acid
      bacteria (LAB) modify the fruity notes of red wines but without a specific trend.
      The absence, in the short term, of a lactic mask was emphasized, whereas the
      existence of a smoked/toasted reduction-like mask note was evoked but not
      characterized. Variations in the composition of the fruity aroma markers were
      predominant. Although LAB beta-glycosidase activities were not very involved, on
      the other hand, esterase seemed to play a central role that was sometimes
      associated with the metabolism of the sulfur-containing compounds. New insights
      in ester metabolism in enological LAB and the importance of wine composition on
      bacterial variations in metabolites and aromatic alterations were emphasized.

PMID- 23163663
TI  - Safety and efficacy of liraglutide in patients with type 2 diabetes and elevated
      liver enzymes: individual patient data meta-analysis of the LEAD program.
AB  - BACKGROUND: Non-alcoholic fatty liver disease has reached epidemic proportions in
      type 2 diabetes (T2D). Glucagon-like peptide-1 analogues are licensed in T2D, yet
      little data exist on efficacy and safety in liver injury. AIM: To assess the
      safety and efficacy of 26-week liraglutide on liver parameters in comparison with
      active-placebo. METHODS: Individual patient data meta-analysis was performed
      using patient-level data combined from six 26-week, phase-III, randomised
      controlled T2D trials, which comprise the 'Liraglutide Effect and Action in
      Diabetes' (LEAD) program. The LEAD-2 sub-study was analysed to assess the effect
      on CT-measured hepatic steatosis. RESULTS: Of 4442 patients analysed, 2241
      (50.8%) patients had an abnormal ALT at baseline [mean ALT 33.8(14.9) IU/L in
      females; 47.3(18.3) IU/L in males]. Liraglutide 1.8 mg reduced ALT in these
      patients vs. placebo (-8.20 vs. -5.01 IU/L; P = 0.003), and was dose-dependent
      (no significant differences vs. placebo with liraglutide 0.6 or 1.2 mg). This
      effect was lost after adjusting for liraglutide's reduction in weight (mean ALT
      difference vs. placebo -1.41 IU/L, P = 0.21) and HbA1c (+0.57 IU/L, P = 0.63).
      Adverse effects with 1.8 mg liraglutide were similar between patients with and
      without baseline abnormal ALT. In LEAD-2 sub-study, liraglutide 1.8 mg showed a
      trend towards improving hepatic steatosis vs. placebo (liver-to-spleen
      attenuation ratio +0.10 vs. 0.00; P = 0.07). This difference was reduced when
      correcting for changes in weight (+0.06, P = 0.25) and HbA(1c)  (0.00, P = 0.93).
      CONCLUSIONS: Twenty-six weeks' liraglutide 1.8 mg is safe, well tolerated and
      improves liver enzymes in patients with type 2 diabetes. This effect appears to
      be mediated by its action on weight loss and glycaemic control.

PMID- 23163665
TI  - Winners and losers, dollars and sense.

PMID- 23163664
TI  - Inhibition of carbonic anhydrase activity modifies the toxicity of doxorubicin
      and melphalan in tumour cells in vitro.
AB  - Carbonic anhydrase IX (CA IX) is a hypoxia-regulated enzyme, overexpressed in
      many types of human cancer. CA IX is involved in pH homeostasis, contributing to
      extracellular acidification and tumourigenesis. Acidification of the
      extracellular milieu can impact upon cellular uptake of chemotherapeutic drugs by
      favouring weak acids (e.g. melphalan), but limiting access of weak bases (e.g.
      doxorubicin). We investigated whether alterations of CA IX activity affected anti
      cancer drug uptake and toxicity. CA inhibitor acetazolamide (AZM) enhanced
      doxorubicin toxicity but reduced melphalan toxicity in cell lines that highly
      expressed CA IX under anoxic conditions (HT29 and MDA435 CA9/18). The toxicity
      changes reflected modification of passive drug uptake. AZM did not alter toxicity
      or uptake in cells with low CA IX activity (HCT116 and MDA435 EV1). AZM lowered
      intracellular pH in HT29 and MDA435 CA9/18 cells under anoxic conditions. CA IX
      activity has chemomodulatory properties and is an attractive target for anti
      cancer therapy.

PMID- 23163666
TI  - Plain packaging of tobacco products--plainly a success.
AB  - Neither health campaigners nor Big Tobacco seem to have any doubt that this will
      beeffective in reducing smoking.

PMID- 23163667
TI  - Looking for value in health care.
AB  - Faced with limited resources, health care systems are obliged to identify low
      value interventions that should not be funded.

PMID- 23163668
TI  - Towards national clinical care standards.

PMID- 23163670
TI  - Gamete donor medical records: whose information is it?
AB  - Is it ethical, moral and feasible to release gamete donors' medical records to
      conceived offspring?

PMID- 23163671
TI  - Learning from journalists' experiences of the H1N1 pandemic.
AB  - Good working relationships with journalists are needed during public health
      crises

PMID- 23163672
TI  - The media and public health: complexity, controversy and combat.
AB  - Public health officials and the media in conflict in their "shadow" roles .

PMID- 23163673
TI  - CareTrack: assessing the appropriateness of health care delivery in Australia.

PMID- 23163674
TI  - CareTrack: assessing the appropriateness of health care delivery in Australia.

PMID- 23163675
TI  - CareTrack: assessing the appropriateness of health care delivery in Australia.

PMID- 23163677
TI  - Time to refocus the homebirth debate.

PMID- 23163678
TI  - Rubella vaccination success in Australia: no time for complacency.

PMID- 23163679
TI  - Influenza vaccination uptake in an Australian hospital: time to make it mandatory
      for health care workers?

PMID- 23163680
TI  - Lost and found: improving ascertainment of refugee-background Australians in
      population datasets.

PMID- 23163681
TI  - Vitamin D and health in adults in Australia and New Zealand: a position
      statement.

PMID- 23163683
TI  - Designing incentives for good-quality hospital care.

PMID- 23163685
TI  - Over 150 potentially low-value health care practices: an Australian study.
AB  - OBJECTIVE: To develop and apply a novel method for scanning a range of sources to
      identify existing health care services (excluding pharmaceuticals) that have
      questionable benefit, and produce a list of services that warrant further
      investigation. DESIGN AND SETTING: A multiplatform approach to identifying
      services listed on the Australian Medicare Benefits Schedule (MBS; fee-for
      service) that comprised: (i) a broad search of peer-reviewed literature on the
      PubMed search platform; (ii) a targeted analysis of databases such as the
      Cochrane Library and National Institute for Health and Clinical Excellence (NICE)
      "do not do" recommendations; and (iii) opportunistic sampling, drawing on our
      previous and ongoing work in this area, and including nominations from clinical
      and non-clinical stakeholder groups. MAIN OUTCOME MEASURES: Non-pharmaceutical,
      MBS-listed health care services that were flagged as potentially unsafe,
      ineffective or otherwise inappropriately applied. RESULTS: A total of 5209
      articles were screened for eligibility, resulting in 156 potentially ineffective
      and/or unsafe services being identified for consideration. The list includes
      examples where practice optimisation (ie, assessing relative value of a service
      against comparators) might be required. CONCLUSION: The list of health care
      services produced provides a launchpad for expert clinical detailing. Exploring
      the dimensions of how, and under what circumstances, the appropriateness of
      certain services has fallen into question, will allow prioritisation within
      health technology reassessment initiatives.

PMID- 23163686
TI  - Crying wolf? Impact of the H1N1 2009 influenza pandemic on anticipated public
      response to a future pandemic.
AB  - OBJECTIVE: To determine changes in public threat perception and anticipated
      compliance with health-protective behaviours in response to a future pandemic;
      using data collected before and after the H1N1 2009 influenza pandemic. DESIGN,
      SETTING AND PARTICIPANTS: Repeat cross-sectional computer-assisted telephone
      surveys with representative samples of the general New South Wales population in
      2007 (2081 participants) and 2010 (2038 participants). MAIN OUTCOME MEASURES:
      Perceived likelihood of a future pandemic in Australia; concern that respondents
      or their families would be affected; degree of change made to life because of the
      possibility of a pandemic; and willingness to comply with health-protective
      behaviours (to be vaccinated, to be isolated if necessary, and to wear a face
      mask). RESULTS: In 2007, 14.9% of the general population considered that an
      influenza pandemic would be highly likely to occur in future; this proportion
      rose to 42.8% in 2010 (odds ratio [OR], 4.96; 95% CI, 3.99-6.16; P < 0.001).
      Conversely, in the same period concern that respondents or their families would
      be directly affected by a future pandemic dropped from 45.5% to 32.5% (OR, 0.57;
      95% CI, 0.44-0.74; P < 0.001). Willingness to be vaccinated against influenza in
      a future pandemic decreased from 75.4% to 64.6% (OR, 0.69; 95% CI, 0.55-0.86; P <
      0.001). A general decrease in willingness to be vaccinated was noted across all
      age groups, most notably for those aged 35-44 years. CONCLUSIONS: Data collected
      before and after the H1N1 2009 influenza pandemic indicated significant shifts in
      public threat perception and anticipated response to a future pandemic. The H1N1
      2009 pandemic has altered public perceptions of the probability of a pandemic in
      the future, but has left the public feeling less vulnerable. Shifts in perception
      have the potential to reduce future public compliance with health-protective
      measures, including critical elements of the public health response, such as
      vaccination.

PMID- 23163687
TI  - Non-melanoma skin cancer in Australia.
AB  - OBJECTIVES: To report the burden and cost of non-melanoma skin cancer (NMSC)
      treatments in Australia and to project estimates of numbers and costs to 2015.
      DESIGN AND SETTING: Retrospective study of data obtained from Medicare Australia
      for NMSC treated by excision, curettage, laser or cryotherapy between 1 January
      1997 and 31 December 2010, by year, sex, age group and state or territory. MAIN
      OUTCOME MEASURES: Total number, total Medicare Benefits Schedule (MBS) benefit
      and total cost in Australian dollars of NMSC treatments. RESULTS: The total
      number of NMSC treatments increased from 412 493 in 1997 to 767 347 in 2010, and
      we estimated that the number of treatments would increase to 938 991 (95% CI, 901
      047-976 934) by 2015. The total MBS benefit for NMSC treatments in 2010 was $93.5
      million, and we estimated that this will increase to $109.8 million (95% CI,
      $105.9-$113.7 million) by 2015, whereas the total cost with inflation (ie, cost
      which includes diagnosis, treatment and pathology) was $511.0 million in 2010,
      estimated to increase to $703.0 million (95% CI, $674.6-$731.4 million) by 2015.
      CONCLUSION: NMSC treatments increased by 86% between 1997 and 2010. We anticipate
      that the number and the total cost without inflation of NMSC treatments will
      increase by a further 22% between 2010 and 2015. NMSC will remain the most costly
      cancer and place an increasing burden on the Australian health care system.

PMID- 23163688
TI  - Reduced emergency calls and improved weekend discharge after introduction of a
      new electronic handover system.
AB  - OBJECTIVES: To measure the frequency and content of electronic handover before
      and after implementation of the Blue BARRWUE handover system, and to measure its
      effect on patient safety and hospital efficiency over weekends. DESIGN, SETTING
      AND PARTICIPANTS: Point-prevalence study comparing outcomes for general medical
      inpatients present over weekends before implementation (1 May 2008 to 30 April
      2009) and after implementation (1 May 2009 to 30 April 2010) of the Blue BARRWUE
      handover system at Geelong Hospital. INTERVENTION: Implementation of the Blue
      BARRWUE handover system and its components (updated working diagnosis,
      background, alerts, resuscitation status, requests, who to do what and when,
      updates and executable discharge plan). MAIN OUTCOME MEASURES: Presence of any
      written handover notes or updated working diagnoses in the BOSSnet clinical
      information system, content of handover notes, frequency of weekend discharges
      and medical emergency team (MET) calls before and after implementation. RESULTS:
      In the 12 months before implementation of the Blue BARRWUE handover system, 976
      patients (47.98%) had a handover note in BOSSnet, versus 1646 patients (95.09%)
      in the 12 months after implementation (P< 0.001; rate ratio [RR], 20.75; 95% CI,
      16.33-26.44). Before implementation, 289 patients (14.21%) were discharged over
      weekends, versus 353 patients (20.39%) after implementation, (P < 0.001; RR,
      1.44; 95% CI, 1.25-1.65). MET calls were made for 152 general medical patients
      before implementation (7.47%), versus 95 general medical patients (5.49%) after
      implementation (P = 0.01; RR, 0.73; 95% CI, 0.57-0.94). CONCLUSIONS: The Blue
      BARRWUE system has sustainably improved written handover in our organisation and
      was associated with improvement in both patient safety and hospital efficiency.

PMID- 23163689
TI  - Guillain-Barre syndrome following pandemic (H1N1) 2009 influenza A immunisation
      in Victoria: a self-controlled case series.
AB  - OBJECTIVES: To determine the relative incidence (RI) of Guillain-Barre syndrome
      (GBS) in a single Australian state following pandemic (H1N1) 2009 influenza A
      immunisation (monovalent vaccine or seasonal trivalent influenza vaccine [TIV])
      in 2009-2010. DESIGN, SETTING AND PARTICIPANTS: Active GBS surveillance (cases
      assessed by two neurologists according to the Brighton criteria) from 30
      September 2009 to 30 September 2010, conducted at 10 hospitals in Victoria,
      Australia. MAIN OUTCOME MEASURES: The RI of GBS in the risk window of 0-42 days
      after vaccination. RESULTS: Sixty-six potential GBS cases were identified, with
      complete data on 50 confirmed cases. The Victorian annual incidence of GBS was
      1.7 per 100 000 population. Three cases had received monovalent vaccine and one
      case had received seasonal TIV within 42 days of symptom onset. The RI of GBS
      following monovalent vaccination was 3.4 (95% CI, 0.8-15.0). For TIV, there was
      one case in the risk period (RI, 0.69; 95% CI, 0.08-5.64). CONCLUSIONS: This is
      the first published study reviewing GBS after a trivalent and/or monovalent
      influenza vaccine containing the pandemic (H1N1) 2009 strain, with only a small
      proportion of GBS cases occurring after influenza immunisation. H1N1-containing
      vaccines were not statistically associated with GBS, but this study could not
      exclude smaller increases in the RI. Active surveillance of adverse events
      following immunisation is required to maintain public and health care
      professional confidence in mass vaccine implementation programs.

PMID- 23163690
TI  - The self-controlled case series method for evaluating safety of vaccines.
AB  - Using cases as their own controls potentially provides stronger evidence for
      analysing adverse events following vaccination.

PMID- 23163691
TI  - Addressing health challenges in a resource-poor setting.

PMID- 23163692
TI  - Them and us.
AB  - Winner, practitioner category, MJA, MDA National, Nossal Global Health Prize.

PMID- 23163693
TI  - Kala-azar: the world's guilty secret.
AB  - The clinic of the Sudan Medical Relief Project (www.sudanmedicalrelief.org) is in
      Old Fangak, in what is now the Republic of South Sudan. In 2010, I spent 7 weeks
      working there with an American medical team, before being evacuated owing to
      increasing violence in the area.

PMID- 23163694
TI  - Kinematic performance of fine motor control in attention-deficit/hyperactivity
      disorder: the effects of comorbid developmental coordination disorder and core
      symptoms.
AB  - BACKGROUND: The aims of this study were: (i) to determine whether differences
      exist in the fine motor fluency and flexibility of three groups (children with
      attention-deficit/hyperactivity disorder [ADHD], children in whom ADHD is
      comorbid with developmental coordination disorder [DCD] [denoted as ADHD+DCD],
      and a typically developing control group); and (ii) to clarify whether the degree
      of severity of core symptoms affects performance. METHODS: The Peabody Picture
      Vocabulary Test-Revised, the Beery-Buktenica Development Test of Visual-Motor
      Integration and the Movement Assessment Battery for Children were used as
      prescreening tests. The Integrated Visual and Auditory+Plus test was utilized to
      assess subjects' attention. The redesigned fine motor tracking and pursuit tasks
      were administered to evaluate subjects' fine motor performance. RESULTS: No
      significant difference was found when comparing the performance of the Children
      with ADHD and the typically developing group. Significant differences existed
      between children in whom ADHD is comorbid with DCD and typically developing
      children. CONCLUSIONS: Children with ADHD demonstrated proper fine motor fluency
      and flexibility, and deficient performance occurred when ADHD was comorbid with
      developmental coordination disorder. Children with ADHD had more difficulty
      implementing closed-loop movements that required higher levels of cognitive
      processing than those of their typically developing peers. Also, deficits in fine
      motor control were more pronounced when ADHD was combined with movement
      coordination problems. The severity of core symptoms had a greater effect on
      children with ADHD's fine motor flexibility than did fluency performance. In
      children with pure ADHD, unsmooth movement performance was highly related to the
      severity of core symptoms.

PMID- 23163696
TI  - The octadecaneuropeptide stimulates somatolactin release from cultured goldfish
      pituitary cells.
AB  - The present study aimed to investigate the distribution of the
      octadecaneuropeptide (ODN) in the goldfish brain and to look for a possible
      effect of ODN on somatolactin (SL) release from pituitary cells. A discrete
      population of ODN-immunoreactive neurones was localised in the lateral part of
      the nucleus lateralis tuberis. These neurones sent projections through the
      neurohypophyseal tract towards the neurohypophysis, and nerve fibres were seen in
      the close vicinity of SL-producing cells in the pars intermedia. Incubation of
      cultured goldfish pituitary cells with graded concentrations of ODN (10(-9) -10(
      5 ) m) induced a dose-dependent stimulation of SL-beta, but not SL-alpha,
      release. ODN-evoked SL release was blocked by the metabotrophic endozepine
      receptor antagonist cyclo(1-8) [DLeu(5) ]OP but was not affected by the central
      type benzodiazepine receptor antagonist flumazenil. ODN-induced SL release was
      suppressed by treatment with the phospholipase C (PLC) inhibitor U-73122 but not
      with the protein kinase A (PKA) inhibitor H-89. These results indicate that, in
      fish, ODN produced by hypothalamic neurones acts as a hypophysiotrophic
      neuropeptide stimulating SL release. The effect of ODN is mediated through a
      metabotrophic endozepine receptor positively coupled to the PLC/inositol 1,4,5
      trisphosphate/protein kinase C-signalling pathway.

PMID- 23163697
TI  - Eradication of Gram-positive and Gram-negative bacteria by photosensitizers
      immobilized in polystyrene.
AB  - Immobilization of photosensitizers in polymers opens prospects for their
      continuous and reusable application. Methylene blue (MB) and Rose Bengal were
      immobilized in polystyrene by mixing solutions of the photosensitizers in
      chloroform with a polymer solution, followed by air evaporation of the solvent.
      This procedure yielded 15-140 MUm polymer films with a porous surface structure.
      The method chosen for immobilization ensured 99% enclosure of the photosensitizer
      in the polymer. The antimicrobial activity of the immobilized photosensitizers
      was tested against Gram-positive and Gram-negative bacteria. It was found that
      both immobilized photosensitizers exhibited high antimicrobial properties, and
      caused by a 1.5-3 log10 reduction in the bacterial concentrations to their total
      eradication. The bactericidal effect of the immobilized photosensitizers depended
      on the cell concentration and on the illumination conditions. Scanning electron
      microscopy was used to prove that immobilized photosensitizers excited by white
      light caused irreversible damage to microbial cells. Photosensitizers immobilized
      on a solid phase can be applied for continuous disinfection of wastewater
      bacteria.

PMID- 23163698
TI  - Express it in numbers: efforts to quantify engineered nanoparticles in
      environmental matrices advance.

PMID- 23163699
TI  - Palladium-catalyzed reactions of enol ethers: access to enals, furans, and
      dihydrofurans.
AB  - The palladium-catalyzed oxidation of alkyl enol ethers to enals, which employs
      low loadings of a palladium catalyst, is described. The mild oxidation conditions
      tolerate a diverse array of functional groups, while allowing the formation of di
      , tri-, and tetrasubtituted olefins. The application of this methodology to
      intramolecular reactions of alkyl enol ethers containing pendant alcohols
      provides furan and 2,5-dihydrofuran products.

PMID- 23163700
TI  - Diverse functional roles of reactive cysteines.
AB  - Cysteine residues on proteins play key roles in catalysis and regulation. These
      functional cysteines serve as active sites for nucleophilic and redox catalysis,
      sites of allosteric regulation, and metal-binding ligands on proteins from
      diverse classes including proteases, kinases, metabolic enzymes, and
      transcription factors. In this review, we focus on a few select examples that
      serve to highlight the multiple functions performed by cysteines, with an
      emphasis on cysteine-mediated protein activities implicated in cancer. The
      enhanced reactivity of functional cysteines renders them susceptible to
      modification by electrophilic species. Toward this end, we discuss recent
      advancements and future prospects for utilizing cysteine-reactive small molecules
      as drugs and imaging agents for the treatment and diagnosis of cancer.

PMID- 23163701
TI  - Combined immunophenotyping and fluorescence in situ hybridization with chromosome
      specific DNA probes allows quantification and differentiation of ex vivo
      generated dendritic cells, leukemia-derived dendritic cells and clonal leukemic
      cells in patients with acute myeloid leukemia.
AB  - Antileukemic T-cell responses induced by leukemia-derived dendritic cells
      (DC(leu)) are variable, due to varying DC/DC(leu) composition/quality. We studied
      DC/DC(leu) composition/quality after blast culture in four DC media by flow
      cytometry (FC) and combined fluorescence in situ hybridization/immunophenotyping
      analysis (FISH-IPA). Both methods showed that DC methods produce variable
      proportions of DC subtypes. FISH-IPA is an elaborate method to study clonal
      aberrations in blast/DC cells on slides, however without preselection of distinct
      cell populations for FISH analysis. FISH-IPA data proved previous FC data: not
      every clonal/blast cell is converted to DC(leu) (resulting in various proportions
      of DC(leu)) and not every detectable DC is of clonal/leukemic origin.
      Preselection of the best of four DC methods for "best" DC/DC(leu) generation is
      necessary. DC(leu) proportions correlate with the antileukemic functionality of
      DC/DC(leu)-stimulated T-cells, thereby proving the necessity of studying the
      quality of DC/DC(leu) after culture. FC is the superior method to quantify
      DC/DC(leu), since a blast phenotype is available in every given patient, even
      with low/no proportions of clonal aberrations, and can easily be used to study
      cellular compositions after DC culture.

PMID- 23163702
TI  - Gastrointestinal AA amyloidosis following allogeneic hematopoietic stem cell
      transplant in a patient with chronic myelogenous leukemia.

PMID- 23163704
TI  - Mechanical bond-induced radical stabilization.
AB  - A homologous series of [2]rotaxanes, in which cyclobis(paraquat-p-phenylene)
      (CBPQT(4+)) serves as the ring component, while the dumbbell components all
      contain single 4,4'-bipyridinium (BIPY(2+)) units centrally located in the midst
      of oligomethylene chains of varying lengths, have been synthesized by taking
      advantage of radical templation and copper-free azide-alkyne 1,3-dipolar
      cycloadditions in the formation of their stoppers. Cyclic voltammetry, UV/vis
      spectroscopy, and mass spectrometry reveal that the BIPY(*+) radical cations in
      this series of [2]rotaxanes are stabilized against oxidation, both
      electrochemically and by atmospheric oxygen. The enforced proximity between the
      BIPY(2+) units in the ring and dumbbell components gives rise to enhanced
      Coulombic repulsion, destabilizing the ground-state co-conformations of the fully
      oxidized forms of these [2]rotaxanes. The smallest [2]rotaxane, with only three
      methylene groups on each side of its dumbbell component, is found to exist under
      ambient conditions in a monoradical state, a situation which does not persist in
      acetonitrile solution, at least in the case of its longer analogues. (1)H NMR
      spectroscopy reveals that the activation energy barriers to the shuttling of the
      CBPQT(4+) rings over the BIPY(2+) units in the dumbbells increase linearly with
      increasing oligomethylene chain lengths across the series of [2]rotaxanes. These
      findings provide a new way of producing highly stabilized BIPY(*+) radical
      cations and open up more opportunities to use stable organic radicals as building
      blocks for the construction of paramagnetic materials and conductive molecular
      electronic devices.

PMID- 23163703
TI  - Foster mother-infant bonding: associations between foster mothers' oxytocin
      production, electrophysiological brain activity, feelings of commitment, and
      caregiving quality.
AB  - This study examined the biological processes associated with foster mother-infant
      bonding. In an examination of foster mother-infant dyads (N = 41, mean infant age
      = 8.5 months), foster mothers' oxytocin production was associated with their
      expressions of behavioral delight toward their foster infant and their average P3
      response to images of all infant faces in the first 2 months of the relationship.
      Three months later, foster mothers' oxytocin production was still associated with
      delight toward their foster infant and was also specifically associated with
      their P3 response to an image of their foster infant. Similar to biologically
      related mothers and infants, oxytocin appears to be associated with foster
      mothers' brain activity and caregiving behavior, with patterns suggestive of bond
      formation.

PMID- 23163705
TI  - Systematic review of record linkage studies of mortality in ex-prisoners: why
      (good) methods matter.
AB  - AIMS: World-wide, more than 30 million people move through prisons annually.
      Record linkage studies have identified an increased risk of death in ex
      prisoners. In order to inform preventive interventions it is necessary to
      understand who is most at risk, when and why. Limitations of existing studies
      have rendered synthesis and interpretation of this literature difficult. The aim
      of this study was to describe methodological characteristics of existing studies
      and make recommendations for the design, analysis and reporting of future
      studies. METHODS: Systematic review of studies using record linkage to explore
      mortality in ex-prisoners. Based on analysis of these studies we illustrate how
      methodological limitations and heterogeneity of design, analysis and reporting
      both hamper data synthesis and create potential for misinterpretation of
      findings. Using data from a recent Australian study involving 42,015 ex-prisoners
      and 2329 observed deaths, we quantify the variation in findings associated with
      various approaches. RESULTS: We identified 29 publications based on 25 separate
      studies published 1998-2011, mainly from the United Kingdom, United States and
      Australia. Mortality estimates varied systematically according to features of
      study design and data analysis. A number of common, avoidable and significant
      methodological limitations were identified. Substantial heterogeneity in study
      design, methods of data analysis and reporting of findings was observed.
      CONCLUSIONS: Record linkage studies examining mortality in ex-prisoners show
      widely varying estimates that are influenced substantially by avoidable
      methodological limitations and reducible heterogeneity. Future studies should
      adopt best practice methods and more consistent methods of analysis and
      reporting, to maximize policy relevance and impact.

PMID- 23163706
TI  - Individual differences in reappraisal effectiveness: the role of affective
      flexibility.
AB  - The present study examined the relation between a specific type of executive
      control and cognitive emotion regulation. The authors propose that successful
      reappraisal is related to "affective flexibility": The ability to flexibly attend
      to and disengage from emotional aspects of a situation or a stimulus. A new
      affective task-switching paradigm that required participants to shift between
      categorizing positive and negative affective pictures according to emotional or
      nonemotional features was used to assess individual differences in affective
      flexibility. The results showed that greater affective flexibility (less switch
      costs) predicted the ability to use reappraisal to down-regulate emotions in
      response to a sad film clip. In particular, more efficient shifts toward the
      neutral aspects of negative pictures and toward the emotional aspects of positive
      pictures were found to predict reappraisal ability. The results imply that
      executive control of emotional material is a capacity that is closely associated
      with effective reappraisal.

PMID- 23163708
TI  - The dark side of intuition: aging and increases in nonoptimal intuitive
      decisions.
AB  - When making decisions, people typically draw on two general modes of thought:
      intuition and reason. Age-related changes in cognition and emotion may impact
      these decision processes: Although older individuals experience declines in
      deliberative processes, they experience stability or improvement in their
      emotional processes. Recent research has shown that when older adults rely more
      on their intact emotional abilities versus their declining deliberative
      faculties, the quality of their decisions is significantly improved. But how
      would older adults fare under circumstances in which intuitive/affective
      processes lead to nonoptimal decisions? The ratio bias paradigm embodies just
      such a circumstance, offering individuals a chance to win money by drawing, say,
      a red jellybean from one of two dishes containing red and white jellybeans.
      People will often choose to draw from a dish with a greater absolute number of
      winners (nine red beans and 91 white beans; 9%) than a dish with a greater
      probability of winning (one red bean and nine white beans; 10%) due to a strong
      emotional pull toward the greater number. We examined whether older adults (N =
      30) would make more nonoptimal decisions on the ratio bias task than young adults
      (N = 30). We found that older adults did make more nonoptimal choices than their
      younger counterparts and that positive affect was associated with nonoptimal
      choices.

PMID- 23163707
TI  - Attenuating age-related learning deficits: emotional valenced feedback interacts
      with task complexity.
AB  - Previous research reveals that older adults sometimes show enhanced processing of
      emotionally positive stimuli relative to negative stimuli, but that this
      positivity bias reverses to become a negativity bias when cognitive control
      resources are less available. In this study, we test the hypothesis that
      emotionally positive feedback will attenuate well-established age-related
      deficits in rule learning whereas emotionally negative feedback will amplify age
      deficits-but that this pattern will reverse when the task involves a high
      cognitive load. Experiment 1 used emotional face feedback and revealed an
      interaction among age, valence of the feedback, and task load. When the task
      placed minimal load on cognitive control resources, happy-face feedback
      attenuated age-related deficits in initial rule learning and angry-face feedback
      led to age-related deficits in initial rule learning and set shifting. However,
      when the task placed a high load on cognitive control resources, we found that
      angry-face feedback attenuated age-related deficits in initial rule learning and
      set shifting whereas happy-face feedback led to age-related deficits in initial
      rule learning and set shifting. Experiment 2 used less emotional point feedback
      and revealed age-related deficits in initial rule learning and set shifting under
      low and high cognitive load for point-gain and point-loss conditions. The
      research presented here demonstrates that emotional feedback can attenuate age
      related learning deficits-but only positive feedback for tasks with a low
      cognitive load and negative feedback for tasks with high cognitive load.

PMID- 23163709
TI  - Happiness is best kept stable: positive emotion variability is associated with
      poorer psychological health.
AB  - Positive emotion has been shown to be associated with adaptive outcomes in a
      number of domains, including psychological health. However, research has largely
      focused on overall levels of positive emotion with less attention paid to how
      variable versus stable it is across time. We thus examined the psychological
      health correlates of positive emotion variability versus stability across 2
      distinct studies, populations, and scientifically validated approaches for
      quantifying variability in emotion across time. Study 1 used a daily experience
      approach in a U.S. community sample (N = 244) to examine positive emotion
      variability across 2 weeks (macrolevel). Study 2 adopted a daily reconstruction
      method in a French adult sample (N = 2,391) to examine variability within 1 day
      (microlevel). Greater macro- and microlevel variability in positive emotion was
      associated with worse psychological health, including lower well-being and life
      satisfaction and greater depression and anxiety (Study 1), and lower daily
      satisfaction, life satisfaction, and happiness (Study 2). Taken together, these
      findings support the notion that positive emotion variability plays an important
      and incremental role in psychological health above and beyond overall levels of
      happiness, and that too much variability might be maladaptive.

PMID- 23163710
TI  - In search of meaningfulness: nostalgia as an antidote to boredom.
AB  - We formulated, tested, and supported, in 6 studies, a theoretical model according
      to which individuals use nostalgia as a way to reinject meaningfulness in their
      lives when they experience boredom. Studies 1-3 established that induced boredom
      causes increases in nostalgia when participants have the opportunity to revert to
      their past. Studies 4 and 5 examined search for meaning as a mediator of the
      effect of boredom on nostalgia. Specifically, Study 4 showed that search for
      meaning mediates the effect of state boredom on nostalgic memory content, whereas
      Study 5 demonstrated that search for meaning mediates the effect of dispositional
      boredom on dispositional nostalgia. Finally, Study 6 examined the meaning
      reestablishment potential of nostalgia during boredom: Nostalgia mediates the
      effect of boredom on sense of meaningfulness and presence of meaning in one's
      life. Nostalgia counteracts the meaninglessness that individuals experience when
      they are bored.

PMID- 23163711
TI  - Revisiting the out-group advantage in emotion recognition in a multicultural
      society: further evidence for the in-group advantage.
AB  - Recent studies have accumulated supporting evidence for in-group advantage in
      emotion recognition, with individuals more accurately perceiving emotions
      expressed by cultural in-group members. However, inconsistent results appear in
      balanced-design studies involving the majority and minority groups residing
      within a single nation: There is an apparent pattern of an out-group advantage,
      implying that minority group members show heightened sensitivity toward emotional
      expressions of the majority group members. Two studies were conducted to further
      explore why the out-group advantage emerged in multicultural societies. In Study
      1, based on a careful review of existing studies involving majority and minority
      groups, both new and previously reviewed, a new approach to assess the in-group
      and out-group advantage was proposed and applied. In Study 2, the minority out
      group advantage was further tested in an experimental study. European American
      and Asian American students were asked to identify emotions of European and Asian
      Americans presented in static photos of imitated emotional expressions and full
      channel video presentations of spontaneous emotional expressions. The results
      revealed that a mutual in-group advantage was observed in the spontaneous
      expressions condition, but not in the imitated expression condition. Significance
      and implications of the findings from this study are discussed regarding
      intergroup interactions in a multicultural society.

PMID- 23163712
TI  - Time-based indicators of emotional complexity: interrelations and correlates.
AB  - Emotional complexity has been regarded as one correlate of adaptive emotion
      regulation in adulthood. One novel and potentially valuable approach to
      operationalizing emotional complexity is to use reports of emotions obtained
      repeatedly in real time, which can generate a number of potential time-based
      indicators of emotional complexity. It is not known, however, how these
      indicators relate to each other, to other measures of affective complexity, such
      as those derived from a cognitive-developmental view of emotional complexity, or
      to measures of adaptive functioning, such as well-being. A sample of 109 adults,
      aged 23 to 90 years, participated in an experience-sampling study and reported
      their negative and positive affect five times a day for one week. Based on these
      reports, we calculated nine different time-based indicators potentially
      reflecting emotional complexity. Analyses showed three major findings: First, the
      indicators showed a diverse pattern of interrelations suggestive of four distinct
      components of emotional complexity. Second, age was generally not related to time
      based indicators of emotional complexity; however, older adults showed overall
      low variability in negative affect. Third, time-based indicators of emotional
      complexity were either unrelated or inversely related to measures of adaptive
      functioning; that is, these measures tended to predict a less adaptive profile,
      such as lower subjective and psychological well-being. In sum, time-based
      indicators of emotional complexity displayed a more complex and less beneficial
      picture than originally thought. In particular, variability in negative affect
      seems to indicate suboptimal adjustments. Future research would benefit from
      collecting empirical data for the interrelations and correlates of time-based
      indicators of emotional complexity in different contexts.

PMID- 23163713
TI  - Emotional faces in context: age differences in recognition accuracy and scanning
      patterns.
AB  - Although age-related declines in facial expression recognition are well
      documented, previous research has relied mostly on isolated faces devoid of
      context. The authors investigated the effects of context on age differences in
      recognition of facial emotions and in visual scanning patterns of emotional
      faces. While their eye movements were monitored, younger and older participants
      viewed facial expressions (i.e., anger, disgust) in contexts that were
      emotionally congruent, incongruent, or neutral to the facial expression to be
      identified. Both age groups had the highest recognition rates of facial
      expressions in the congruent context, followed by the neutral context, and
      recognition rates in the incongruent context were the lowest. These context
      effects were more pronounced for older adults. Compared to younger adults, older
      adults exhibited a greater benefit from congruent contextual information,
      regardless of facial expression. Context also influenced the pattern of visual
      scanning characteristics of emotional faces in a similar manner across age
      groups. In addition, older adults initially attended more to context overall. Our
      data highlight the importance of considering the role of context in understanding
      emotion recognition in adulthood.

PMID- 23163715
TI  - Relevance is in the eye of the beholder: attentional bias to relevant stimuli in
      children.
AB  - Attentional biases are most often framed in a threat relevance framework.
      Alternatively, it could be that not only threat-related stimuli draw attention
      but also that preferential attention is drawn to all stimuli that have relevance
      for an individual. We investigated this stimulus relevance theory in primary
      school-age children by means of a visual search task. As predicted, children
      displayed attentional biases toward evolutionary and modern threat-related
      stimuli, such as spiders and guns, but also toward other relevant, positive
      stimuli (i.e., cakes, gifts, and happy faces). These results suggest that
      attentional biases are not specific to threat, but seem to apply to all relevant
      stimuli, both positive and negative in valence, providing first evidence for the
      stimulus relevance theory of preferential attention in children.

PMID- 23163716
TI  - Gold nanorods as plasmonic nanotransducers: distance-dependent refractive index
      sensitivity.
AB  - Owing to the facile tunability of the localized surface plasmon resonance
      wavelength (LSPR) and large refractive index sensitivity, gold nanorods (AuNR)
      are of high interest as plasmonic nanotransducers for label-free biological
      sensing. We investigate the influence of gold nanorod dimensions on distance
      dependent LSPR sensitivity and electromagnetic (EM) decay length using
      electrostatic layer-by-layer (LbL) assembly of polyelectrolytes. The
      electromagnetic decay length was found to increase linearly with both nanorod
      length and diameter, although to variable degrees. The rate of EM decay length
      increase with nanorod diameter is significantly higher compared to that of the
      length, indicating that diameter is a convenient handle to tune the EM decay
      length of gold nanorods. The ability to precisely measure the EM decay length of
      nanostructures enables the rational selection of plasmonic nanotransducer
      dimensions for the particular biosensing application.

PMID- 23163714
TI  - The effect of modifying automatic action tendencies on overt avoidance behaviors.
AB  - We used the Approach-Avoidance Task (AAT) to examine the role of automatic action
      tendencies. We hypothesized that, after manipulation of automatic action
      tendencies, participants would be more likely to approach feared objects when
      compared with participants in a control condition. Participants were instructed
      to push or pull a joystick, resulting in contamination-related and neutral
      pictures moving progressively away from or toward them, respectively. We
      manipulated approach by building a contingency between the arm movement and the
      picture type in the active condition but not in the control condition. Consistent
      with our hypothesis, participants in the active manipulation group showed
      facilitated automatic approach tendencies and reduced avoidance tendencies for
      contamination-related stimuli and completed more steps approaching their feared
      objects in a behavioral approach test compared with participants in the control
      group. Our results suggest that automatic action tendencies may play an important
      role in the maintenance of fear-related behavioral avoidance.

PMID- 23163717
TI  - Distinctive clinical features of idiopathic versus infectious serpiginous
      choroidopathy.
AB  - PURPOSE: Serpiginous choroidopathy (SC) is an inflammatory disease of unknown
      etiology. Infectious diseases that mimic SC are termed serpiginous-like
      choroidopathy (SLC). The aim of this study is to determine the clinical features
      of infectious SLC in comparison to SC. METHODS: Multicenter case series.
      Variables analyzed were age, gender, laterality, visual acuity, intraocular
      inflammation, multifocal pattern, choroidal neovascularization, involvement of
      juxtapapillary area, and posterior pole. Statistical significance was assessed by
      Mann-Whitney U test and Fisher's exact test. RESULTS: Twenty-four patients had SC
      and 5 patients had SLC. Mean ages were 50 and 46 years (SC and SLC,
      respectively). In the SC group, 54% of the patients were males, and in the SC
      group, 80% were males. The disease was bilateral in 87.5% in the SC group and in
      80% in the SLC group. The juxtapapillary area was involved in 91% in SC eyes and
      0% in the SLC group (p < .05). CONCLUSIONS: In cases where the peripapillary area
      is disease-free, an infectious etiology has to be strongly suspected, as an
      immunomodulatory treatment could have severe consequences.

PMID- 23163718
TI  - Decreased disability is associated with improved perceived quality of life
      following spinal fusion.
AB  - PURPOSE: To assess the disability and relationship between functional status and
      health related quality of life (HRQoL) in patients in the early recovery phase
      following spinal fusion. METHODS: This is a prospective cohort study. Since 2008
      data of spinal fusion patients have been collected prospectively in two Finnish
      hospitals. In August 2009, complete data of 173 patients were available. The
      measurement tool of disability was the Oswestry Disability Index (ODI) and it was
      also examined in the framework of International Classification of Functioning,
      Disability and Health (ICF) using body functions and structures, activities and
      participation components. RESULTS: Preoperatively the mean total ODI was 45
      (SD17) and mean (95% confidence interval) change to 3 months postoperatively was 
      19 (-22 to -17). When the ODI was linked to the ICF, there was a 55% improvement
      in the body structure and functions component and a 44% improvement in both the
      activities and the participation components. However, 25% of the patients still
      had the total ODI score over 40 three months postoperatively. Preoperatively, the
      mean (95% CI) Physical Component Summary Score (PCS) of the Short Form 36
      questionnaire (SF-36) was 27 (26 to 28) and the mean Mental Component Summary
      Score (MCS) of SF-36 was 47 (45 to 49). Postoperatively the improvement was 9
      (95% CI: 8 to 11) in PCS and 6 (95% CI: 4 to 7) in MCS (p < 0.001). CONCLUSIONS:
      Spinal fusion is successful in the early recovery period in terms of reduction of
      pain and disability. The significant changes in the ODI were seen in all three
      components of the ICF model. In addition, improvement in functioning was
      significantly related to positive change in HRQoL. Still there is a subgroup of
      patients having marked disability needing more intensive rehabilitation and
      follow-ups.

PMID- 23163719
TI  - Capacity for care: meta-ethnography of acute care nurses' experiences of the
      nurse-patient relationship.
AB  - AIMS: To synthesize evidence and knowledge from published research about nurses'
      experiences of nurse-patient relationships with adult patients in general, acute
      inpatient hospital settings. BACKGROUND: While primary research on nurses'
      experiences has been reported, it has not been previously synthesized. DESIGN:
      Meta-ethnography. DATA SOURCES: Published literature from Australia, Europe, and
      North America, written in English between January 1999-October 2009 was
      identified from databases: CINAHL, Medline, British Nursing Index and PsycINFO.
      REVIEW METHODS: Qualitative studies describing nurses' experiences of the nurse
      patient relationship in acute hospital settings were reviewed and synthesized
      using the meta-ethnographic method. RESULTS: Sixteen primary studies (18 papers)
      were appraised as high quality and met the inclusion criteria. The findings show
      that while nurses aspire to develop therapeutic relationships with patients, the
      organizational setting at a unit level is strongly associated with nurses'
      capacity to build and sustain these relationships. The organizational conditions
      of critical care settings appear best suited to forming therapeutic
      relationships, while nurses working on general wards are more likely to report
      moral distress resulting from delivering unsatisfactory care. General ward nurses
      can then withdraw from attempting to emotionally engage with patients.
      CONCLUSION: The findings of this meta-ethnography draw together the evidence from
      several qualitative studies and articulate how the organizational setting at a
      unit level can strongly influence nurses' capacity to build and sustain
      therapeutic relationships with patients. Service improvements need to focus on
      how to optimize the organizational conditions that support nurses in their
      relational work with patients.

PMID- 23163720
TI  - Microwave-assisted synthesis of antimicrobial agents based on pyridazine moiety.
AB  - An efficient and simple microwave assisted synthesis of sulfonamide derivatives
      incorporating the pyridazine moiety has been developed. These sulfonamides were
      used for the preparation of new heterocyclic compounds via reaction with
      different reagents using a microwave irradiation technique. The structures of the
      newly synthesized compounds were confirmed on the basis of FTIR, (1)H and (13)C
      NMR, mass spectral techniques and elemental analyses. Some of the new synthesized
      compounds were assayed for their in vitro antibacterial activity against Gram
      positive bacteria, Staphylococcus aureus and Staphylococcus epidermidis, Gram
      negative bacteria, Escherichia coli and Klebsiella pneumonia and antifungal
      activity against Aspergillus fumigatus and Candida albicans. Most of the new
      compounds showed significant antibacterial and antifungal activity. 

PMID- 23163721
TI  - Mixed glioneuronal tumor: a dysembryoplastic neuroepithelial tumor with rosette
      forming glioneuronal tumor component.
AB  - Neuronal and mixed neuronal-glial tumors of the CNS show a wide spectrum of
      components. Here, we report an unusual case of brain tumor with combined
      histological features of dysembryoplastic neuroepithelial tumor (DNT) and rosette
      forming glioneuronal tumor (RGNT) in a 23-year-old man. It arose in the left
      anterior cingulate cortex with a pseudo-polycystic appearance on neuroimaging.
      Histological features contained the "specific glioneuronal element" mimicking DNT
      and the components of distinct neurocytic rosettes with a center of neuropil
      islands and pilocytic astrocytoma resembling RGNT. Although the mechanisms of
      mixed glioneuronal tumor are far from being well-known, their co-existence might
      suggest a possible etiologic relationship between DNT and RGNT. 

PMID- 23163722
TI  - Introduction to the special issue on the risk of extreme and catastrophic events.

PMID- 23163723
TI  - Strategic preparedness for recovery from catastrophic risks to communities and
      infrastructure systems of systems.
AB  - Natural and human-induced disasters affect organizations in myriad ways because
      of the inherent interconnectedness and interdependencies among human, cyber, and
      physical infrastructures, but more importantly, because organizations depend on
      the effectiveness of people and on the leadership they provide to the
      organizations they serve and represent. These human-organizational-cyber-physical
      infrastructure entities are termed systems of systems. Given the multiple
      perspectives that characterize them, they cannot be modeled effectively with a
      single model. The focus of this article is: (i) the centrality of the states of a
      system in modeling; (ii) the efficacious role of shared states in modeling
      systems of systems, in identification, and in the meta-modeling of systems of
      systems; and (iii) the contributions of the above to strategic preparedness,
      response to, and recovery from catastrophic risk to such systems. Strategic
      preparedness connotes a decision-making process and its associated actions. These
      must be: implemented in advance of a natural or human-induced disaster, aimed at
      reducing consequences (e.g., recovery time, community suffering, and cost),
      and/or controlling their likelihood to a level considered acceptable (through the
      decisionmakers' implicit and explicit acceptance of various risks and tradeoffs).
      The inoperability input-output model (IIM), which is grounded on Leontief's
      input/output model, has enabled the modeling of interdependent subsystems. Two
      separate modeling structures are introduced. These are: phantom system models
      (PSM), where shared states constitute the essence of modeling coupled systems;
      and the IIM, where interdependencies among sectors of the economy are manifested
      by the Leontief matrix of technological coefficients. This article demonstrates
      the potential contributions of these two models to each other, and thus to more
      informative modeling of systems of systems schema. The contributions of shared
      states to this modeling and to systems identification are presented with case
      studies.

PMID- 23163724
TI  - Improving default risk prediction using Bayesian model uncertainty techniques.
AB  - Credit risk is the potential exposure of a creditor to an obligor's failure or
      refusal to repay the debt in principal or interest. The potential of exposure is
      measured in terms of probability of default. Many models have been developed to
      estimate credit risk, with rating agencies dating back to the 19th century. They
      provide their assessment of probability of default and transition probabilities
      of various firms in their annual reports. Regulatory capital requirements for
      credit risk outlined by the Basel Committee on Banking Supervision have made it
      essential for banks and financial institutions to develop sophisticated models in
      an attempt to measure credit risk with higher accuracy. The Bayesian framework
      proposed in this article uses the techniques developed in physical sciences and
      engineering for dealing with model uncertainty and expert accuracy to obtain
      improved estimates of credit risk and associated uncertainties. The approach uses
      estimates from one or more rating agencies and incorporates their historical
      accuracy (past performance data) in estimating future default risk and transition
      probabilities. Several examples demonstrate that the proposed methodology can
      assess default probability with accuracy exceeding the estimations of all the
      individual models. Moreover, the methodology accounts for potentially significant
      departures from "nominal predictions" due to "upsetting events" such as the 2008
      global banking crisis.

PMID- 23163726
TI  - The structure and properties of septin 3: a possible missing link in septin
      filament formation.
AB  - The human genome codes for 13 members of a family of filament-forming GTP-binding
      proteins known as septins. These have been divided into four different subgroups
      on the basis of sequence similarity. The differences between the subgroups are
      believed to control their correct assembly into heterofilaments which have
      specific roles in membrane remodelling events. Many different combinations of the
      13 proteins are theoretically possible and it is therefore important to
      understand the structural basis of specific filament assembly. However, three
      dimensional structures are currently available for only three of the four
      subgroups. In the present study we describe the crystal structure of a construct
      of human SEPT3 which belongs to the outstanding subgroup. This construct (SEPT3
      GC), which includes the GTP-binding and C-terminal domains, purifies as a
      nucleotide-free monomer, allowing for its characterization in terms of GTP
      binding and hydrolysis. In the crystal structure, SEPT3-GC forms foreshortened
      filaments which employ the same NC and G interfaces observed in the
      heterotrimeric complex of human septins 2, 6 and 7, reinforcing the notion of
      'promiscuous' interactions described previously. In the present study we describe
      these two interfaces and relate the structure to its tendency to form monomers
      and its efficiency in the hydrolysis of GTP. The relevance of these results is
      emphasized by the fact that septins from the SEPT3 subgroup may be important
      determinants of polymerization by occupying the terminal position in octameric
      units which themselves form the building blocks of at least some heterofilaments.

PMID- 23163725
TI  - Lung cancer with loss of BRG1/BRM, shows epithelial mesenchymal transition
      phenotype and distinct histologic and genetic features.
AB  - BRG1 and BRM, two core catalytic subunits in SWI/SNF chromatin remodeling
      complexes, have been suggested as tumor suppressors, yet their roles in
      carcinogenesis are unclear. Here, we present evidence that loss of BRG1 and BRM
      is involved in the progression of lung adenocarcinomas. Analysis of 15 lung
      cancer cell lines indicated that BRG1 mutations correlated with loss of BRG1
      expression and that loss of BRG1 and BRM expression was frequent in E-cadherin
      low and vimentin-high cell lines. Immunohistochemical analysis of 93 primary lung
      adenocarcinomas showed loss of BRG1 and BRM in 11 (12%) and 16 (17%) cases,
      respectively. Loss of expression of BRG1 and BRM was frequent in solid
      predominant adenocarcinomas and tumors with low thyroid transcription factor-1
      (TTF-1, master regulator of lung) and low cytokeratin7 and E-cadherin (two
      markers for bronchial epithelial differentiation). Loss of BRG1 was correlated
      with the absence of lepidic growth patterns and was mutually exclusive of
      epidermal growth factor receptor (EGFR) mutations. In contrast, loss of BRM was
      found concomitant with lepidic growth patterns and EGFR mutations. Finally, we
      analyzed the publicly available dataset of 442 cases and found that loss of BRG1
      and BRM was frequent in E-cadherin-low, TTF-1-low, and vimentin-high cases and
      correlated with poor prognosis. We conclude that loss of either or both BRG1 and
      BRM is involved in the progression of lung adenocarcinoma into solid predominant
      tumors with features of epithelial mesenchymal transition and loss of the
      bronchial epithelial phenotype. BRG1 loss was specifically involved in the
      progression of EGFR wild-type, but not EGFR-mutant tumors.

PMID- 23163727
TI  - Application of ultrahigh-performance liquid chromatography and electrospray
      ionization quadrupole orbitrap high-resolution mass spectrometry for
      determination of 166 pesticides in fruits and vegetables.
AB  - This paper presents an application of ultrahigh-performance liquid chromatography
      and electrospray ionization quadrupole Orbitrap high-resolution mass spectrometry
      (UHPLC/ESI Q-Orbitrap) for determination of 166 pesticide residues in fruits and
      vegetables. Pesticides were extracted from the samples using the QuEChERS (quick,
      easy, cheap, effective, rugged, and safe) procedure. UHPLC/ESI Q-Orbitrap MS
      (i.e., full MS scan) acquired full MS data for quantification, and UHPLC/ESI Q
      Orbitrap dd-MS(2) (i.e., data-dependent scan) obtained product-ion spectra for
      confirmation. UHPLC/ESI Q-Orbitrap MS quantification was achieved using matrix
      matched standard calibration curves with isotopically labeled standards or
      chemical analogues as internal standards. The method performance characteristics
      that included overall recovery, intermediate precision, and measurement
      uncertainty were evaluated according to a nested experimental design. For the
      matrices studied, about 90.3-91.5% of the pesticides had recoveries between 81
      and 110%, 92.1-97.6% had intermediate precision <=20%, and 89.7-95.2% had
      measurement uncertainty <=40%. Confirmation was based on mass accuracy <=5 ppm
      and LC retention time tolerance within +/-2.5%. Overall, the UHPLC/ESI Q-Orbitrap
      has demonstrated great performance for quantification and confirmation of
      pesticide residues in fresh fruits and vegetables.

PMID- 23163728
TI  - Review of the key results from the Swedish Obese Subjects (SOS) trial - a
      prospective controlled intervention study of bariatric surgery.
AB  - Obesity is a risk factor for diabetes, cardiovascular disease events, cancer and
      overall mortality. Weight loss may protect against these conditions, but robust
      evidence for this has been lacking. The Swedish Obese Subjects (SOS) study is the
      first long-term, prospective, controlled trial to provide information on the
      effects of bariatric surgery on the incidence of these objective endpoints. The
      SOS study involved 2010 obese subjects who underwent bariatric surgery [gastric
      bypass (13%), banding (19%) and vertical banded gastroplasty (68%)] and 2037
      contemporaneously matched obese control subjects receiving usual care. The age of
      participants was 37-60 years and body mass index (BMI) was >=34 kg m(-2)  in men
      and >=38 kg m(-2)  in women. Here, we review the key SOS study results published
      between 2004 and 2012. Follow-up periods varied from 10 to 20 years in different
      reports. The mean changes in body weight after 2, 10, 15 and 20 years were -23%, 
      17%, -16% and -18% in the surgery group and 0%, 1%, -1% and -1% in the control
      group respectively. Compared with usual care, bariatric surgery was associated
      with a long-term reduction in overall mortality (primary endpoint) [adjusted
      hazard ratio (HR) = 0.71, 95% confidence interval (CI) 0.54-0.92; P = 0.01] and
      decreased incidences of diabetes (adjusted HR=0.17; P < 0.001), myocardial
      infarction (adjusted HR = 0.71; P = 0.02), stroke (adjusted HR=0.66; P = 0.008)
      and cancer (women: adjusted HR = 0.58; P = 0.0008; men: n.s.]. The diabetes
      remission rate was increased severalfold at 2 years [adjusted odds ratio (OR) =
      8.42; P < 0.001] and 10 years (adjusted OR = 3.45; P < 0.001). Whereas high
      insulin and/or high glucose at baseline predicted favourable treatment effects,
      high baseline BMI did not, indicating that current selection criteria for
      bariatric surgery need to be revised.

PMID- 23163729
TI  - Applying crime scene analysis to the prediction of sexual recidivism in stranger
      rapes.
AB  - The current study sought to improve the predictive accuracy of sexual recidivism
      using the Static-99 risk assessment tool by the addition of detailed crime scene
      analysis (CSA). CSA was carried out using a Behavioral Thematic Analysis (BTA)
      approach, the gold-standard in CSA. BTA was conducted on a sample of 167 stranger
      rape cases using nonmetric multidimensional scaling (MDS). The BTA procedure
      revealed three behavioral themes of hostility, criminality, and sexual
      exploitation, consistent with previous research in sexual offending CSA. Logistic
      regression analysis indicated that the criminality theme was significantly
      predictive of sexual recidivism and also significantly correlated with previous
      sexual offense history. Further, the criminality theme led to a significant
      increase in the incremental validity of the Static-99 actuarial risk assessment
      instrument for the prediction of sexual recidivism.

PMID- 23163730
TI  - Recognizing new perspectives in eating difficulties following stroke: a concept
      analysis.
AB  - PURPOSE: To describe and identify various perspectives on eating difficulties
      following stroke to enable theory development and facilitate advancement of
      interventions. METHODS: Concept analysis in line with Morse's principles of
      exploring pragmatic utility was used throughout the data collection and analysis.
      Peer-reviewed research on eating difficulties was systematically and critically
      appraised. Literature included the bibliographic databases, Medline, Cumulative
      Index to Nursing and Allied Health Literature (CINAHL), Scopus and PsycInfo,
      published up until November 2011. A total of 33 key articles were included in the
      final analysis. RESULTS: A conceptual model of eating difficulties is presented
      showing the multiple affecting factors, namely meaning-related, functional and
      contextual factors and the consequences of non-intervention, feeling of loss,
      social isolation, negative sensations and depression - all of which potentially
      increase the impact of disease severity, functional outcome and quality of life.
      Based upon the dimensions identified, the definition of eating difficulties was
      synthesized as "any activity and emotional requirement and relations, which alone
      or in combination interfere with the process of preparing food, transferring food
      into the mouth, chewing and swallowing". CONCLUSION: Eating difficulties have
      profound effects on people. The conceptual model serves to guide health care
      professionals to assess and help stroke patients in facing a life with eating
      difficulties.

PMID- 23163731
TI  - Mapping the structure of semantic memory.
AB  - Aggregating snippets from the semantic memories of many individuals may not yield
      a good map of an individual's semantic memory. The authors analyze the structure
      of semantic networks that they sampled from individuals through a new snowball
      sampling paradigm during approximately 6 weeks of 1-hr daily sessions. The
      semantic networks of individuals have a small-world structure with short
      distances between words and high clustering. The distribution of links follows a
      power law truncated by an exponential cutoff, meaning that most words are poorly
      connected and a minority of words has a high, although bounded, number of
      connections. Existing aggregate networks mirror the individual link
      distributions, and so they are not scale-free, as has been previously assumed;
      still, there are properties of individual structure that the aggregate networks
      do not reflect. A simulation of the new sampling process suggests that it can
      uncover the true structure of an individual's semantic memory.

PMID- 23163732
TI  - Orbital inflammatory disease: unusual presentation of enthesitis in an HLA-B27
      spondyloarthropathy.
AB  - BACKGROUND: Orbital inflammatory disease can complicate many systemic
      inflammatory disorders, including sarcoidosis, vasculitis, Crohn's disease,
      systemic lupus erythematosus, rheumatoid arthritis, myasthenia gravis and
      scleroderma, but has not been reported with spondyloarthropathies. OBSERVATIONS:
      The authors describe a 29-year-old woman who developed orbital myositis, in
      addition to anterior uveitis, sacroiliitis and peripheral arthritis, as a
      complication of an underlying HLA-B27 related spondyloarthropathy, which
      responded temporarily to corticosteroid therapy and more completely to
      adalimumab. CONCLUSIONS: The patient reported herein presents with orbital
      inflammation as an extra-articular manifestation of HLA-B27 associated
      undifferentiated spondyloarthropathy. We propose that enthesitis is the likely
      mechanism of orbital inflammation in this patient.

PMID- 23163734
TI  - Efficient oxidative cycloreversion reaction of photochromic dithiazolythiazole.
AB  - Electrochemical response of photochromic tearylenes was surveyed by means of
      cyclic voltammetry, DFT calculations, and spectroelectrochemistry. 4,5-Bis(2
      phenyl-5-methylthiazolyl)-2-phenylthiazole was found to show electrochemical
      oxidative ring-cycloreversion reaction. The net current efficiency of the
      cycloreversion reaction under constant potential electrolysis was as high as
      900%, which is ascribed to an electrochemical local-cell mechanism and a chain
      reaction mechanism. Electron transfer stopped-flow study using a chemical oxidant
      successfully identified radical cation intermediates of both closed- and open
      ring isomers, involved in the oxidative cycloreversion process. The significantly
      long-lived radical cation of open-ring isomer with the lifetime of 33 s takes
      part in the indirect electron transfer process from the neutral closed-ring
      isomer to the radical cation of open-ring isomer in the chain reaction manner.

PMID- 23163733
TI  - Cu(II)-catalyzed aerobic hydroperoxidation of Meldrum's acid derivatives and
      application in intramolecular oxidation: a conceptual blueprint for O2/H2
      dihydroxylation.
AB  - Aerobic hydroperoxidation of Meldrum's acid derivatives via a Cu(II)-catalyzed
      process is presented. The mild reaction conditions are tolerant to pendant
      unsaturation allowing the formation of endoperoxides via electrophilic
      activation. Cleavage of the O-O bond provides 1,n-diols with differentiation of
      the hydroxy groups.

PMID- 23163735
TI  - One year weight loss in the TRAMOMTANA study. A randomized controlled trial.
AB  - BACKGROUND: Morbid obesity is a major health problem and bariatric surgery is
      currently the most effective therapy available to induce weight loss in these
      patients. This report describes 1-year changes in weight and metabolic
      parameters, in a trial designed to examine the effects of a nonsurgical approach,
      Intensive Life style Intervention (ILI) on the therapy of morbid obesity.
      METHODS: The primary outcome was change in body weight. Patients were randomized
      to ILI (n = 60) or conventional obesity therapy (COT) (n = 46). The ILI group
      received behavioural therapy and nutritional/physical activity counselling. The
      COT group received the standard medical treatment available for these patients. A
      third group consisted of the patients already included in our bariatric surgery
      waiting list (n = 37). FINDINGS: We present here 1-year data showing that
      patients who received ILI with no restrictions in calorie intake had a greater
      percentage of weight loss than patients receiving COT (-11.58% vs -0.4%; P <
      0.001). Importantly, 31.4% of patients included in the ILI group were not
      morbidly obese after 6 months of intervention. This number increased to 42.8%
      after 12 months of intervention. INTERPRETATION: ILI was associated with
      significant weight loss compared with COT in a group of morbidly obese patients.
      The weight loss effect was already obtained after 6 months of ILI intervention.
      These results seriously question the efficacy of the COT approach to morbid
      obesity. Furthermore, they underscore the use of ILI programmes in the hospital
      setting to effectively treat morbidly obese patients and might help to reduce the
      number of candidate patients for bariatric surgery.

PMID- 23163736
TI  - Electronic communication across diamagnetic metal bridges: a homoleptic
      gallium(III) complex of a redox-active diarylamido-based ligand and its oxidized
      derivatives.
AB  - Complexes with cations of the type [Ga(L)(2)](n+) where L = bis(4-methyl-2-(1H
      pyrazol-1-yl)phenyl)amido and n = 1, 2, 3 have been prepared and structurally
      characterized. The electronic properties of each were probed by electrochemical
      and spectroscopic means and were interpreted with the aid of density functional
      theory (DFT) calculations. The dication, best described as [Ga(L(-))(L(0))](2+),
      is a Robin-Day class II mixed-valence species. As such, a broad, weak, solvent
      dependent intervalence charge transfer (IVCT) band was found in the NIR spectrum
      in the range 6390-6925 cm(-1), depending on the solvent. Band shape analyses and
      the use of Hush and Marcus relations revealed a modest electronic coupling, H(ab)
      of about 200 cm(-1), and a large rate constant for electron transfer, k(et), on
      the order of 10(10) s(-1) between redox active ligands. The dioxidized complex
      [Ga(L(0))(2)](3+) shows a half-field DeltaM(s) = 2 transition in its solid-state
      X-band electron paramagnetic resonance (EPR) spectrum at 5 K, which indicates
      that the triplet state is thermally populated. DFT calculations (M06/Def2-SV(P))
      suggest that the singlet state is 21.7 cm(-1) lower in energy than the triplet
      state.

PMID- 23163737
TI  - Fabrication of chitosan-poly(ethylene glycol) hybrid hydrogel microparticles via
      replica molding and its application toward facile conjugation of biomolecules.
AB  - We demonstrate a facile scheme to fabricate nonspherical chitosan-poly(ethylene
      glycol) (PEG) microparticle platforms for conjugation of biomolecules with high
      surface density. Specifically, we show that PEG microparticles containing short
      chitosan oligomers are readily fabricated via replica molding (RM). Fluorescence
      and FTIR microscopy results illustrate that these chitosan moieties are
      incorporated with PEG networks in a stable manner while retaining chemical
      reactivity toward amine-reactive chemistries. The chitosan-PEG particles are then
      conjugated with single-stranded (ss) DNAs via Cu-free click chemistry.
      Fluorescence and confocal microscopy results show facile conjugation of
      biomolecules with the chitosan-PEG particles under mild conditions with high
      selectivity. These ssDNA-conjugated chitosan-PEG particles are then enlisted to
      assemble tobacco mosaic virus (TMV) via nucleic acid hybridization as an example
      of orientationally controlled conjugation of supramolecular targets. Results
      clearly show controllable TMV assembly with high surface density, indicating high
      surface DNA density on the particles. Combined, these results demonstrate a
      facile fabrication-conjugation scheme for robust biomolecular conjugation or
      assembly platforms. We expect that our approach can be enlisted in a wide array
      of biomolecular targets and applications.

PMID- 23163738
TI  - Developmental changes in infant spatial categorization: when more is best and
      when less is enough.
AB  - Two experiments examined infants' ability to form a spatial category when
      habituated to few (only 2) or many (6) exemplars of a spatial relation. Sixty
      four infants of 10 months and 64 infants of 14 months were habituated to dynamic
      events in which a toy was placed in a consistent spatial relation (in or on) to a
      referent object. At 10 months, infants formed a spatial category (looking longer
      at an unfamiliar than familiarized spatial relation) only when habituated to 6
      exemplars. At 14 months, infants formed the spatial category regardless of the
      number of habituation exemplars. The results highlight developmental changes in
      infant spatial categorization and show that increasing exemplar number
      facilitates this ability in infants of 10 months.

PMID- 23163739
TI  - Lower urinary tract symptoms in patients with Niigata Minamata disease: a case
      control study 50 years after methyl mercury pollution.
AB  - OBJECTIVES: To clarify the prevalence of lower urinary tract symptoms and
      overactive bladder in patients with chronic methyl mercury poisoning. METHODS: A
      total of 151 patients (61 men and 90 women; mean age 72.1 years) with Niigata
      Minamata disease were enrolled. An age- and sex-matched group of 150 participants
      was used as control. Patients reported their International Prostate Symptom Score
      and overactive bladder symptom score. RESULTS: In men, the total, storage and
      voiding International Prostate Symptom Score scores were higher in the Niigata
      Minamata disease group than in the control group (10.6 +/- 7.8 vs 5.0 +/- 5.0,
      4.5 +/- 3.3 vs 2.4 +/- 2.4 and 6.1 +/- 5.1 vs 2.7 +/- 3.1, respectively, P <
      0.001 in all). In women, these scores were also higher in the Niigata Minamata
      disease group than in the control group (8.9 +/- 7.3 vs 4.0 +/- 4.0, 4.4 +/- 3.2
      vs 2.8 +/- 2.4 and 4.5 +/- 5.0 vs 1.3 +/- 2.0, respectively, P < 0.001 in all).
      The prevalence of overactive bladder was more frequent in the Niigata Minamata
      disease group compared with that in the control group (51.7% vs 26.7%, P <
      0.001). In both men and women, the overactive bladder symptom score was higher in
      the Niigata Minamata disease group than in the control group (4.1 +/- 3.0 vs 2.4
      +/- 2.9, P = 0.002 and 4.6 +/- 3.6 vs 2.7 +/- 2.9, P < 0.001, respectively). The
      International Prostate Symptom Score and overactive bladder symptom score in the
      Niigata Minamata disease group were highest in patients aged 60-69 years (P <
      0.001 in both), whereas these increased in an age-dependent manner in the control
      group. CONCLUSIONS: Lower urinary tract symptoms and overactive bladder are
      severe and highly prevalent conditions among patients with methyl mercury
      poisoning. The higher prevalence of lower urinary tract symptoms among patients
      aged 60-69 years might be related to the fact that they were exposed to methyl
      mercury during their childhood/development.

PMID- 23163740
TI  - Chemical detoxification of small molecules by Caenorhabditis elegans.
AB  - Caenorhabditis elegans lives in compost and decaying fruit, eats bacteria and is
      exposed to pathogenic microbes. We show that C. elegans is able to modify diverse
      microbial small-molecule toxins via both O- and N-glucosylation as well as
      unusual 3'-O-phosphorylation of the resulting glucosides. The resulting
      glucosylated derivatives have significantly reduced toxicity to C. elegans,
      suggesting that these chemical modifications represent a general mechanism for
      worms to detoxify their environments.

PMID- 23163741
TI  - Establishing the clinical and economic benefits of adherence to 5-alpha reductase
      inhibitors in benign prostatic hyperplasia: an assessment of Medicare and
      Medicaid patients.
AB  - OBJECTIVE: The primary objective of this study was to evaluate the length of 5
      alpha reductase inhibitor (5ARI) therapy on the likelihood of acute urinary
      retention (AUR) and prostate surgery in patients diagnosed with benign prostatic
      hyperplasia (BPH). Additionally, this study attempted to quantify the
      relationship between length of 5ARI therapy and monthly BPH-related medical
      costs. STUDY DESIGN: This study used MarketScan(r) claims data from January 1,
      2003, to December 31, 2008. Male Medicare patients >= 65 years and Medicaid
      patients >= 50 years who received a diagnosis of BPH and at least one claim for a
      5ARI during the study period were included. Cox proportional hazards models were
      used to evaluate the effect of length of therapy on AUR and surgery, whereas
      generalized linear models were used to assess the effect on costs. RESULTS: In
      28,903 patients, every additional 30 days of 5ARI therapy reduced the likelihood
      of AUR and prostate surgery by 14 and 11%, respectively, while each 30-day
      increment of 5ARI therapy reduced BPH-related costs by 15%. CONCLUSION: For
      patients remaining on 5ARI therapy, significant clinical and economic benefits
      may be realized, including reductions in AUR and prostate surgery rates and
      reduced medical costs for these clinical events.

PMID- 23163742
TI  - Bimolecular fluorescence complementation and interaction of various Arabidopsis
      major intrinsic proteins expressed in yeast.
AB  - Tonoplast intrinsic proteins (TIPs) and plasma membrane intrinsic proteins (PIPs)
      form subgroups of plant major intrinsic proteins (MIPs) that channel water as
      well as various small neutral molecules across the tonoplast and plasma membrane.
      Most MIPs are believed to form homotetramers, while some plant PIPs have been
      shown to form heterotetramers composed of different isoforms. This study
      investigated in vivo molecular interactions between different Arabidopsis TIP
      isoforms and between TIPs and a PIP member. The interactions were assayed by
      bimolecular fluorescence complementation optimized for use in Saccharomyces
      cerevisiae as a heterologous expression system. Fluorescence of re-assembled
      Venus yellow fluorescent protein was monitored by fluorescence microscopy and
      flow cytometry. The results showed strong interactions between TIP1;2, TIP2;1 and
      TIP3;1. Surprisingly, the three TIP isoforms also interacted with PIP2;1. The
      potassium channel AKT1 was used as a negative control and exhibited no
      interaction with any of the MIPs. The observed interactions may play a role in
      targeting and regulation of MIPs in plants.

PMID- 23163743
TI  - Release behavior and stability of encapsulated D-limonene from emulsion-based
      edible films.
AB  - Edible films may act as carriers of active molecules, such as flavors. This
      possibility confers to them the status of active packaging. Two different film
      forming biopolymers, gluten and iota-carrageenans, have been compared. D-Limonene
      was added to the two film formulations, and its release kinetics from emulsion
      based edible films was assessed with HS-SPME. Results obtained for edible films
      were compared with D-limonene released from the fatty matrix called Grindsted
      Barrier System 2000 (GBS). Comparing iota-carrageenans with gluten-emulsified
      film, the latter showed more interesting encapsulating properties: in fact, D
      limonene was retained by gluten film during the process needed for film
      preparation, and it was released gradually during analysis time. D-Limonene did
      not show great affinity to iota-carrageenans film, maybe due to high aroma
      compound hydrophobicity. Carvone release from the three different matrices was
      also measured to verify the effect of oxygen barrier performances of edible films
      to prevent D-limonene oxidation. Further investigations were carried out by FT-IR
      and liquid permeability measurements. Gluten film seemed to better protect D
      limonene from oxidation. Gluten-based edible films represent an interesting
      opportunity as active packaging: they could retain and release aroma compounds
      gradually, showing different mechanical and nutritional properties from those of
      lipid-based ingredients.

PMID- 23163744
TI  - High expression of KIBRA in low atypical protein kinase C-expressing gastric
      cancer correlates with lymphatic invasion and poor prognosis.
AB  - Overexpression of atypical protein kinase Clambda/iota (aPKClambda/iota), a
      regulator of cell polarity, is frequently associated with the poor prognoses of
      several cancers, including gastric cancer. Recent studies revealed a molecular
      link between aPKC and KIBRA, an upstream regulator of tumor suppressor Hippo
      pathway that regulates cell proliferation and apoptosis. Further, KIBRA directly
      inhibits the kinase activity of aPKC to regulate epithelial cell polarity. These
      observations suggest that the KIBRA-aPKC connection plays a role in cancer
      progression; however, clinical significance of the correlation between these
      factors remains unclear. Here we examined the correlation between
      KIBRA/aPKClambda/iota expression, as detected by immunohistochemistry, and
      clinicopathological outcomes in 164 gastric cancer patients using Fisher's exact
      test and Kaplan-Meier log-rank test. We found an intimate correlation between the
      expression level of KIBRA and aPKClambda/iota (P = 0.012). Furthermore, high
      expression of KIBRA is correlated with lymphatic (P = 0.046) and venous invasion
      (P = 0.039). The expression level of KIBRA by itself did not correlate with the
      prognosis; however, high expression of KIBRA in low aPKClambda/iota-expressing
      gastric cancer correlated with disease-specific (P = 0.037) and relapse-free
      survival (P = 0.041) by Kaplan-Meier with log-rank test and higher lymphatic
      invasion cases by Fisher's exact test (P = 0.042). Furthermore, overexpression of
      the aPKC-binding region of KIBRA disrupted tight junctions in epithelial cells.
      These results suggest that high expression of KIBRA in low aPKC-expressing cells
      causes massive loss of aPKC activity, leading to loss of polarity and
      invasiveness of gastric cancer cells.

PMID- 23163745
TI  - Abstracts of Neurofly 2012. September 3-7, 2012. Padua, Italy.

PMID- 23163746
TI  - In vitro and in vivo studies of galactose-modified liver-targeting liposomes.
AB  - Oridonin (ORI) is a bioactive diterpenoid compound extracted from the well known
      Chinese traditional medicine Rabdosia rubescens. The aim of this study was to
      prepare ORI loaded liposomes surface-modified with galactose (NOH-ORI-LP) and
      evaluate their characteristics compared with ORI loaded liposomes (ORI-LP) and
      ORI solution in vitro and in vivo. The NOH-ORI-LP was prepared by ethanol
      injection method. The NOH-ORI-LP was characterized by their morphology, particle
      size, zeta potential and encapsulation efficiency. The concentration of ORI in
      plasma and tissues at different sampling time points were determined. The liver
      concentration-time curves of NOH-ORI-LP in mice were determined, and the
      pharmacokinetic parameters were calculated and compared by statistical analysis.
      Our data revealed that NOH-ORI-LP has a particle size of about (173 +/- 12) nm.
      The particles exhibit a negative electrical charge (-31.5 +/- 1.6 mV), and
      possess high encapsulation efficiency (94.1 +/- 1.2%). There were significantly
      different parameters of k(10) and area under the plasma concentration-time curve
      (AUC(0-t)) between liposomes and solution. The mean residence time (MRT(0-t)) in
      plasma of NOH-ORI-LP was 5.56 times longer than that of solution. Compared with
      solution, NOH-ORI-LP delivered about 4.28 times higher ORI into liver. Thus, an
      optimum intravenous galactose-modified liposome formulation for ORI could be
      developed as an alternative to the commercial ORI preparations.

PMID- 23163747
TI  - Two ways to the top: evidence that dominance and prestige are distinct yet viable
      avenues to social rank and influence.
AB  - The pursuit of social rank is a recurrent and pervasive challenge faced by
      individuals in all human societies. Yet, the precise means through which
      individuals compete for social standing remains unclear. In 2 studies, we
      investigated the impact of 2 fundamental strategies-Dominance (the use of force
      and intimidation to induce fear) and Prestige (the sharing of expertise or know
      how to gain respect)-on the attainment of social rank, which we conceptualized as
      the acquisition of (a) perceived influence over others (Study 1), (b) actual
      influence over others' behaviors (Study 1), and (c) others' visual attention
      (Study 2). Study 1 examined the process of hierarchy formation among a group of
      previously unacquainted individuals, who provided round-robin judgments of each
      other after completing a group task. Results indicated that the adoption of
      either a Dominance or Prestige strategy promoted perceptions of greater
      influence, by both group members and outside observers, and higher levels of
      actual influence, based on a behavioral measure. These effects were not driven by
      popularity; in fact, those who adopted a Prestige strategy were viewed as
      likable, whereas those who adopted a Dominance strategy were not well liked. In
      Study 2, participants viewed brief video clips of group interactions from Study 1
      while their gaze was monitored with an eye tracker. Dominant and Prestigious
      targets each received greater visual attention than targets low on either
      dimension. Together, these findings demonstrate that Dominance and Prestige are
      distinct yet viable strategies for ascending the social hierarchy, consistent
      with evolutionary theory.

PMID- 23163748
TI  - Presumed fair: ironic effects of organizational diversity structures.
AB  - This research tests the hypothesis that the presence (vs. absence) of
      organizational diversity structures causes high-status group members (Whites,
      men) to perceive organizations with diversity structures as procedurally fairer
      environments for underrepresented groups (racial minorities, women), even when it
      is clear that underrepresented groups have been unfairly disadvantaged within
      these organizations. Furthermore, this illusory sense of fairness derived from
      the mere presence of diversity structures causes high-status group members to
      legitimize the status quo by becoming less sensitive to discrimination targeted
      at underrepresented groups and reacting more harshly toward underrepresented
      group members who claim discrimination. Six experiments support these hypotheses
      in designs using 4 types of diversity structures (diversity policies, diversity
      training, diversity awards, idiosyncratically generated diversity structures from
      participants' own organizations) among 2 high-status groups in tests involving
      several types of discrimination (discriminatory promotion practices, adverse
      impact in hiring, wage discrimination). Implications of these experiments for
      organizational diversity and employment discrimination law are discussed.

PMID- 23163749
TI  - Predicting persons' versus a person's goodness: behavioral forecasts diverge for
      individuals versus populations.
AB  - Behavioral forecasts of individuals ("How likely is it a randomly selected person
      will...") and behavioral forecasts of populations ("What percentage of people
      will...") are often used interchangeably. However, 6 studies showed that
      behavioral forecasts of individuals and populations systematically differ. In
      judgments of morally relevant behaviors, forecasters estimated that a randomly
      selected individual (e.g., a student) would act more selflessly (e.g., give to
      charity) than would the population from which the individual was drawn (e.g., the
      student body). The studies provided consistent support for 1 of 5 possible
      explanations for the effect, a differential sensitivity to constraints
      hypothesis. When considering how an individual will behave, people give weight to
      an individual-level force on behavior: what an individual's moral conscience
      would lead one to do. When considering a population, forecasters give more
      emphasis to a group-level force on behavior: social norms and pressures. A final
      study extended the differential sensitivity to constraints account to forecasts
      of non-morally relevant behaviors. Individuals were forecast as more likely than
      populations to perform behaviors that emerge primarily because of an individual
      level force-a person's will-but not behaviors that are encouraged by social
      norms.

PMID- 23163750
TI  - The causal structure of utility conditionals.
AB  - The psychology of reasoning is increasingly considering agents' values and
      preferences, achieving greater integration with judgment and decision making,
      social cognition, and moral reasoning. Some of this research investigates utility
      conditionals, ''if p then q'' statements where the realization of p or q or both
      is valued by some agents. Various approaches to utility conditionals share the
      assumption that reasoners make inferences from utility conditionals based on the
      comparison between the utility of p and the expected utility of q. This article
      introduces a new parameter in this analysis, the underlying causal structure of
      the conditional. Four experiments showed that causal structure moderated utility
      informed conditional reasoning. These inferences were strongly invited when the
      underlying structure of the conditional was causal, and significantly less so
      when the underlying structure of the conditional was diagnostic. This asymmetry
      was only observed for conditionals in which the utility of q was clear, and
      disappeared when the utility of q was unclear. Thus, an adequate account of
      utility-informed inferences conditional reasoning requires three components:
      utility, probability, and causal structure.

PMID- 23163751
TI  - Specific dietary preferences are linked to differing gut microbial metabolic
      activity in response to dark chocolate intake.
AB  - Systems biology approaches are providing novel insights into the role of
      nutrition for the management of health and disease. In the present study, we
      investigated if dietary preference for dark chocolate in healthy subjects may
      lead to different metabolic response to daily chocolate consumption. Using NMR-
      and MS-based metabolic profiling of blood plasma and urine, we monitored the
      metabolic response of 10 participants stratified as chocolate desiring and eating
      regularly dark chocolate (CD) and 10 participants stratified as chocolate
      indifferent and eating rarely dark chocolate (CI) to a daily consumption of 50 g
      of dark chocolate as part of a standardized diet over a one week period. We
      demonstrated that preference for chocolate leads to different metabolic response
      to chocolate consumption. Daily intake of dark chocolate significantly increased
      HDL cholesterol by 6% and decreased polyunsaturated acyl ether phospholipids.
      Dark chocolate intake could also induce an improvement in the metabolism of long
      chain fatty acid, as noted by a compositional change in plasma fatty acyl
      carnitines. Moreover, a relationship between regular long-term dietary exposure
      to a small amount of dark chocolate, gut microbiota, and phenolics was
      highlighted, providing novel insights into biological processes associated with
      cocoa bioactives.

PMID- 23163752
TI  - Metal insertion into the molybdenum cofactor: product-substrate channelling
      demonstrates the functional origin of domain fusion in gephyrin.
AB  - The complexity of eukaryotic multicellular organisms relies on evolutionary
      developments that include compartmentalization, alternative splicing, protein
      domain fusion and post-translational modification. Mammalian gephyrin uniquely
      exemplifies these processes by combining two enzymatic functions within the
      biosynthesis of the Moco (molybdenum cofactor) in a multidomain protein. It also
      undergoes extensive alternative splicing, especially in neurons, where it also
      functions as a scaffold protein at inhibitory synapses. Two out of three gephyrin
      domains are homologous to bacterial Moco-synthetic proteins (G and E domain)
      while being fused by a third gephyrin-specific central C domain. In the present
      paper, we have established the in vitro Moco synthesis using purified components
      and demonstrated an over 300-fold increase in Moco synthesis for gephyrin
      compared with the isolated G domain, which synthesizes adenylylated
      molybdopterin, and E domain, which catalyses the metal insertion at physiological
      molybdate concentrations in an ATP-dependent manner. We show that the C domain
      impacts the catalytic efficacy of gephyrin, suggesting an important structural
      role in product-substrate channelling as depicted by a structural model that is
      in line with a face-to-face orientation of both active sites. Our functional
      studies demonstrate the evolutionary advantage of domain fusion in metabolic
      proteins, which can lead to the development of novel functions in higher
      eukaryotes.

PMID- 23163753
TI  - Increased prolidase activity and oxidative stress in PCOS.
AB  - AIM: Matrix metalloproteinases (MMPs) have been considered to have a role in
      various pathological processes, including inflammatory response, cardiovascular
      disease and recently also in ovarian dysfunction. Since prolidase could be
      accepted as a matrix metalloproteinase, on the biochemical level, we aimed to
      evaluate serum prolidase activity and oxidative-antioxidative status in patients
      with polycystic ovary syndrome (PCOS) and healthy individuals. MATERIALS AND
      METHODS: Thirty-three PCOS patients and 28 healthy nonhyperandrogenic women were
      studied. Levels of prolidase activity, total antioxidant status (TAS), total
      oxidant status (TOS), oxidative stress index (OSI), luteinizing hormone (LH),
      follicle-stimulating hormone (FSH), total testosterone (T) and prolactin (PRL)
      were calculated. RESULTS: Levels of prolidase activities, total oxidant status,
      oxidative stress index, LH, PRL, and T were significantly higher in PCOS group
      than in the control group. Total antioxidant status levels were lower in PCOS
      group than healthy group, but it was not statistically significant. There was no
      significant difference between PCOS and control groups in term of FSH.
      CONCLUSION: Women with PCOS have increased serum prolidase activity and oxidative
      stress. It might be hypothesized that elevated serum prolidase activity and
      oxidative stress may be associated with increased cardiovascular risk in PCOS
      and/or menstrual irregularities associated with this syndrome.

PMID- 23163754
TI  - Vogt-Koyanagi-Harada disease in Thailand.
AB  - PURPOSE: To determine clinical characteristics and rate of ocular complications
      in patients with Vogt-Koyanagi-Harada disease (VKH). METHODS: The authors
      performed a retrospective review of 48 consecutive patients (92 affected eyes)
      diagnosed with VKH. Demographic data, clinical manifestations, treatment
      modalities, and ocular complications were registered. RESULTS: VKH constituted
      approximately 10% of all new encounters of uveitis patients. Ocular complications
      developed in 49/92 (53%) eyes. The most frequent complication was cataract (45%),
      followed by glaucoma (29%). The presence of ocular complications was not
      associated with stage of the disease at presentation (p = .654) or the treatment
      modalities (p = .261). Recurrent inflammation developed in 13% and was not
      associated with initial intravenous corticosteroids or use of immunosuppressive
      drugs (p = .614 and p = 1.000). CONCLUSIONS: Cataract and glaucoma represented
      the common ocular complications of VKH. Recurrences developed solely in 13% of
      patients and were not associated with a specific treatment regimen but with an
      early withdrawal of systemic corticosteroids.

PMID- 23163755
TI  - Quantum mechanical transition-state analysis reveals the precise origin of
      stereoselectivity in chiral quaternary cinchonidinium phase-transfer catalyzed
      enolate allylation.
AB  - Density functional theory was used to model glycinate enolate binding and
      enantiomeric allylation transition states mediated by the cinchonidinium phase
      transfer catalyst 2. Transition states show oxy-anion-ammonium interactions in
      contrast to pi-face interactions in the ground states. The details of
      stereoselectivity are described within the quaternary ammonium-tetrahedron face
      model.

PMID- 23163756
TI  - A heterogeneous nickel catalyst for the hydrogenolysis of aryl ethers without
      arene hydrogenation.
AB  - A heterogeneous nickel catalyst for the selective hydrogenolysis of aryl ethers
      to arenes and alcohols generated without an added dative ligand is described. The
      catalyst is formed in situ from the well-defined soluble nickel precursor
      Ni(COD)(2) or Ni(CH(2)TMS)(2)(TMEDA) in the presence of a base additive, such as
      (t)BuONa. The catalyst selectively cleaves C(Ar)-O bonds in aryl ether models of
      lignin without hydrogenation of aromatic rings, and it operates at loadings down
      to 0.25 mol % at 1 bar of H(2) pressure. The selectivity of this catalyst for
      electronically varied aryl ethers differs from that of the homogeneous catalyst
      reported previously, implying that the two catalysts are distinct from each
      other.

PMID- 23163757
TI  - Development of intra- and intergroup judgments in the context of moral and social
      conventional norms.
AB  - Children and adolescents evaluated group inclusion and exclusion in the context
      of generic and group-specific norms involving morality and social conventions.
      Participants (N = 381), aged 9.5 and 13.5 years, judged an in-group member's
      decision to deviate from the norms of the group, whom to include, and whether
      their personal preference was the same as what they expected a group should do.
      Deviating from in-group moral norms about unequal allocation of resources was
      viewed more positively than deviating from conventional norms about
      nontraditional dress codes. With age, participants gave priority to group
      specific norms and differentiated what the group should do from their own
      preference about the group's decision, revealing a developmental picture about
      children's complex understanding of group dynamics and group norms.

PMID- 23163758
TI  - Effect of number and location of distant metastases on renal cell carcinoma
      mortality in candidates for cytoreductive nephrectomy: implications for
      multimodal therapy.
AB  - OBJECTIVE: To test whether the combination of number and location of distant
      metastases affects cancer-specific survival in patients with metastatic renal
      cell carcinoma. METHODS: Overall, 242 metastatic renal cell carcinoma patients
      with synchronous metastases at diagnosis underwent cytoreductive nephrectomy at a
      single institution. Combinations of number and location of distant metastases
      were coded as: single metastasis and single organ affected, multiple metastases
      and single organ affected, single metastasis for each of the multiple organs
      affected, and multiple metastases for each of the multiple organs affected.
      Covariates included age, symptoms, performance status, American Society of
      Anesthesiologists score, hemoglobin, lactate dehydrogenase, tumor size, Fuhrman
      grade, T stage, lymph node status, necrosis, sarcomatoid features and
      metastasectomy at the time of nephrectomy. RESULTS: The median survival was 34.7
      versus 32.3 versus 29.6 versus 8.5 months for single metastasis and single organ
      affected, multiple metastases and single organ affected single metastasis for
      each of the multiple organs affected, and multiple metastases for each of the
      multiple organs affected patients, respectively. At multivariable analyses, the
      combination of number and location of distant metastases resulted in one of the
      most informative and independent predictors of cancer-specific survival in
      metastatic renal cell carcinoma patients. The lung was the location with the
      highest rate of single organ affected (50.3% vs 35.1% in other sites; P < 0.001).
      Considering only patients with a single metastasis, no statistically
      significantly different cancer-specific survival rates were recorded (P > 0.3)
      among different metastatic organs. CONCLUSIONS: Among metastatic renal cell
      carcinoma patients undergoing cytoreductive nephrectomy, the combination of the
      number and location of distant metastases is a major independent predictor of
      cancer-specific survival. Patients with multiple organs affected by multifocal
      disease are more likely to have poorer survival.

PMID- 23163759
TI  - Outer-sphere coordination chemistry: amido-ammonium ligands as highly selective
      tetrachloridozinc(II)ate extractants.
AB  - Eight new amido functionalized reagents, L(1)-L(8), have been synthesized
      containing the sequence of atoms R(2)N-CH(2)-NR'-CO-R", which upon protonation
      forms a six-membered chelate with a hydrogen bond between the tertiary ammonium N
      H(+) group and the amido oxygen atom. The monocationic ligands, LH(+), extract
      tetrachloridometal(II)ates from acidic solutions containing high concentrations
      of chloride ions via a mechanism in which two ligands address the "outer sphere"
      of the [MCl(4)](2-) unit using both N-H and C-H hydrogen bond donors to form the
      neutral complex as in 2L + 2HCl + MCl(2) ? [(LH)(2)MCl(4)]. The strengths of L(1)
      L(8) as zinc extractants in these pH-dependent equilibria have been shown to be
      very dependent on the number of amide groups in the R(3-n)N(CH(2)NR'COR")(n)
      molecules, anti-intuitively decreasing with the number of strong hydrogen bond
      donors present and following the order monoamides > diamides > triamides. Studies
      of the effects of chloride concentration on extraction have demonstrated that the
      monoamides in particular show an unusually high selectivity for [ZnCl(4)](2-)
      over [FeCl(4)](-) and Cl(-). Hybrid-DFT calculations on the tri-, di-, and
      monoamides, L(2), L(3), and L(4), help to rationalize these orders of strength
      and selectivity. The monoamide L(4) has the most favorable protonation energy
      because formation of the LH(+) cation generates a "chelated proton" structure as
      described above without having to sacrifice an existing intramolecular amide
      amide hydrogen bond. The selectivity of extraction of [ZnCl(4)](2-) over Cl(-),
      represented by the process 2[(LH)Cl] + ZnCl(4)(2-) ? [(LH)(2)ZnCl(4)] + 2Cl(-),
      is most favorable for L(4) because it is less effective at binding chloride as it
      has fewer highly polar N-H hydrogen bond donor groups to interact with this
      "hard" anion.

PMID- 23163760
TI  - 2D NMR-based metabolomics uncovers interactions between conserved biochemical
      pathways in the model organism Caenorhabditis elegans.
AB  - Ascarosides are small-molecule signals that play a central role in C. elegans
      biology, including dauer formation, aging, and social behaviors, but many aspects
      of their biosynthesis remain unknown. Using automated 2D NMR-based comparative
      metabolomics, we identified ascaroside ethanolamides as shunt metabolites in C.
      elegans mutants of daf-22, a gene with homology to mammalian 3-ketoacyl-CoA
      thiolases predicted to function in conserved peroxisomal lipid beta-oxidation.
      Two groups of ethanolamides feature beta-keto functionalization confirming the
      predicted role of daf-22 in ascaroside biosynthesis, whereas alpha-methyl
      substitution points to unexpected inclusion of methylmalonate at a late stage in
      the biosynthesis of long-chain fatty acids in C. elegans. We show that ascaroside
      ethanolamide formation in response to defects in daf-22 and other peroxisomal
      genes is associated with severe depletion of endocannabinoid pools. These results
      indicate unexpected interaction between peroxisomal lipid beta-oxidation and the
      biosynthesis of endocannabinoids, which are major regulators of lifespan in C.
      elegans. Our study demonstrates the utility of unbiased comparative metabolomics
      for investigating biochemical networks in metazoans.

PMID- 23163763
TI  - Tracking the time course of word-frequency effects in auditory word recognition
      with event-related potentials.
AB  - Although the word-frequency effect is one of the most established findings in
      spoken-word recognition, the precise processing locus of this effect is still a
      topic of debate. In this study, we used event-related potentials (ERPs) to track
      the time course of the word-frequency effect. In addition, the neighborhood
      density effect, which is known to reflect mechanisms involved in word
      identification, was also examined. The ERP data showed a clear frequency effect
      as early as 350 ms from word onset on the P350, followed by a later effect at
      word offset on the late N400. A neighborhood density effect was also found at an
      early stage of spoken-word processing on the PMN, and at word offset on the late
      N400. Overall, our ERP differences for word frequency suggest that frequency
      affects the core processes of word identification starting from the initial phase
      of lexical activation and including target word selection. They thus rule out any
      interpretation of the word frequency effect that is limited to a purely
      decisional locus after word identification has been completed.

PMID- 23163762
TI  - Ataxia telangiectasia mutated-dependent regulation of topoisomerase II alpha
      expression and sensitivity to topoisomerase II inhibitor.
AB  - Topoisomerase II alpha (TOP2A) has a crucial role in proper chromosome
      condensation and segregation. Here we report the interaction of TOP2A with ataxia
      telangiectasia mutated (ATM) and its phosphorylation in an ATM-dependent manner
      after DNA damage. In vitro kinase assay and site-directed mutagenesis studies
      revealed that serine 1512 is the target of phosphorylation through ATM. Serine
      1512 to Alanine mutation of TOP2A showed increased stability of the protein,
      retaining TOP2A activity at least with regard to cell survival activity. Ataxia
      telangiectasia-derived cell lines showed high levels of TOP2A that were
      associated with hypersensitivity to the TOP2 inhibitor etoposide. These findings
      suggest that ATM-dependent TOP2A modification is required for proper regulation
      of TOP2 stability and subsequently of the sensitivity to TOP2 inhibitor. In a
      lymphoblastoid cell line derived from a patient who developed MLL rearrangement,
      positive infant leukemia, defective ATM expression, and increased TOP2A
      expression were shown. It was intriguing that hypersensitivity to TOP2 inhibitor
      and susceptibility to MLL gene rearrangement were shown by low-dose etoposide
      exposure in this cell line. Thus, our findings have clinically important
      implications for the pathogenesis of infantile acute leukemia as well as
      treatment-associated secondary leukemia following exposure to TOP2 inhibitors.

PMID- 23163764
TI  - UV-irradiation provokes generation of superoxide on cell wall polygalacturonic
      acid.
AB  - We examined the redox effects of UV irradiation on cell wall isolates from Pisum
      sativum leaves, and polygalacturonic and galacturonic acid, in the presence of
      hydrogen peroxide. For this purpose, electron paramagnetic resonance spectroscopy
      and two spin-traps (DEPMPO and BMPO), capable of differentiating between various
      free radicals, were applied. Systems were exposed to UV-B (maximum emission at
      312 nm) and UV-A (352 nm) for 10 min (6 J m(-2) s(-1)). Cell wall isolates
      exposed to UV in the presence of hydrogen peroxide, produced hydroxyl radical,
      carbon dioxide radical and superoxide. The production of superoxide was observed
      for cell wall isolates, polygalacturonic acid (in the presence and in the absence
      of calcium) and galacturonic acid, and it was diminished upon superoxide
      dismutase supplementation. The production is at least partially based on the
      reaction of hydroxyl radicals with (poly)galacturonic acid having carbon dioxide
      radicals as a products. Acting as a strong reducing agent, carbon dioxide radical
      reacts with molecular oxygen to produce superoxide. The results presented here
      shed a new light on: (1) the redox-modulating role of cell wall; (2) the
      production of superoxide in the extracellular compartment; (3) the mechanisms
      involved in translating UV stress into molecular signaling and (4) some other UV
      related phenomena in plants, such as CO(2) emission.

PMID- 23163765
TI  - Hysteresis affects approximate number discrimination in young children.
AB  - Perceptual decisions are often affected not only by the evidence gathered during
      a trial but also by the history of preceding trials. This effect--termed
      perceptual hysteresis--provides evidence for how perceptual information is
      represented and how it is used. The present research focuses on how the
      difficulty of preceding trials affects subsequent ones--we find that how well 5
      year-old children perform in a 2-alternative forced-choice numerical
      discrimination task depends on whether they have had a prior history of easier
      discriminations or a prior history of harder discriminations. Furthermore, this
      effect is modulated by the feedback children receive. In 3 experiments, we
      demonstrate that these effects are not related to practice or loss of interest
      due to negative feedback, or simply to trial difficulty or discriminability.
      Instead, children appear to have state-dependent confidence states such that
      prolonged experience making low-confidence decisions degrades performance,
      whereas prolonged experience making high-confidence decisions improves it. These
      results are discussed in the context of dynamical psychophysics, representations
      of confidence, and work on children's and adults' number perception abilities.

PMID- 23163766
TI  - Bayesian parametric estimation of stop-signal reaction time distributions.
AB  - The cognitive concept of response inhibition can be measured with the stop-signal
      paradigm. In this paradigm, participants perform a 2-choice response time (RT)
      task where, on some of the trials, the primary task is interrupted by a stop
      signal that prompts participants to withhold their response. The dependent
      variable of interest is the latency of the unobservable stop response (stop
      signal reaction time, or SSRT). Based on the horse race model (Logan & Cowan,
      1984), several methods have been developed to estimate SSRTs. None of these
      approaches allow for the accurate estimation of the entire distribution of SSRTs.
      Here we introduce a Bayesian parametric approach that addresses this limitation.
      Our method is based on the assumptions of the horse race model and rests on the
      concept of censored distributions. We treat response inhibition as a censoring
      mechanism, where the distribution of RTs on the primary task (go RTs) is censored
      by the distribution of SSRTs. The method assumes that go RTs and SSRTs are ex
      Gaussian distributed and uses Markov chain Monte Carlo sampling to obtain
      posterior distributions for the model parameters. The method can be applied to
      individual as well as hierarchical data structures. We present the results of a
      number of parameter recovery and robustness studies and apply our approach to
      published data from a stop-signal experiment.

PMID- 23163767
TI  - Emotion regulation choice: a conceptual framework and supporting evidence.
AB  - Choice behavior is considered the fundamental means by which individuals exert
      control over their environments. One important choice domain that remains
      virtually unexplored is that of emotion regulation. This is surprising given that
      healthy adaptation requires flexibly choosing between regulation strategies in a
      manner that is responsive to differing situational demands. In the present
      article, we provide a broad conceptual framework that systematically evaluates
      the rules that govern the ways individuals choose between different emotion
      regulation strategies. This conceptual account is buttressed by empirical
      findings from 6 studies that show the effects of hypothesized emotional,
      cognitive, and motivational determinants of regulation choice (Studies 1-3) and
      illuminate the mechanisms that underlie choices between different emotion
      regulation strategies (Studies 4-6). Broad implications and future directions are
      discussed.

PMID- 23163769
TI  - Potent and specific bactericidal effect of juglone (5-hydroxy-1,4-naphthoquinone)
      on the fire blight pathogen Erwinia amylovora.
AB  - A screening of plant quinones for inhibiting effects on the bacterial fire blight
      pathogen Erwinia amylovora was performed. The most active compound, juglone from
      walnuts, has a potent and specific bactericidal effect on E. amylovora and
      minimal inhibitory concentrations of only 2.5-10 MUM, with stronger effects at
      lower, but still physiological, pH values. In vitro tests with juglone and
      inoculated flowers of apple (Malus domestica) showed an efficacy of 67% in
      preventing infection. In two years of field tests juglone had variable degrees of
      efficacy ranging from 40 to 82%, seemingly due to environmental conditions. A
      phytotoxic reaction to juglone, which is known for its allelopathic effect on
      plants, was restricted to browning of petals; later fruit russeting was not
      observed. Juglone is a promising candidate for the development of a new
      environmentally friendly plant protectant to replace the antibiotic streptomycin
      currently used in fire blight control.

PMID- 23163770
TI  - Diastereoselective reductive ring expansion of spiroketal dihydropyranones to cis
      fused bicyclic ethers.
AB  - A novel double cascade synthetic strategy was developed for the
      diastereoselective syntheses of cis-fused bicyclic ethers, featuring cascade
      Achmatowicz rearrangement/spiroketalization and cascade spiroketal reduction/oxa
      Michael cyclization. Especially, the chemo-, regio-, and diastereoselective
      reduction of densely functionalized spiroketal dihydropyranones, followed by oxa
      Michael cyclization in a one-pot fashion, was achieved.

PMID- 23163768
TI  - Receptors, endocytosis, and trafficking: the biological basis of targeted
      delivery of antisense and siRNA oligonucleotides.
AB  - The problem of targeted delivery of antisense and siRNA oligonucleotides can be
      resolved into two distinct aspects. The first concerns devising ligand
      oligonucleotide or ligand-carrier moieties that bind with high selectivity to
      receptors on the cell type of interest and that are efficiently internalized by
      endocytosis. The second concerns releasing oligonucleotides from
      pharmacologically inert endomembrane compartments so that they can access RNA in
      the cytosol or nucleus. In this review, we will address both of these aspects.
      Thus, we present information on three important receptor families, the integrins,
      the receptor tyrosine kinases, and the G protein-coupled receptors in terms of
      their suitability for targeted delivery of oligonucleotides. This includes
      discussion of receptor abundance, internalization and trafficking pathways, and
      the availability of suitable high affinity ligands. We also consider the process
      of oligonucleotide uptake and intracellular trafficking and discuss approaches to
      modulating these processes in a pharmacologically productive manner. Hopefully,
      the basic information presented in this review will be of value to investigators
      involved in designing delivery approaches for oligonucleotides.

PMID- 23163771
TI  - Crystal structure of hexanoyl-CoA bound to beta-ketoacyl reductase FabG4 of
      Mycobacterium tuberculosis.
AB  - FabGs, or beta-oxoacyl reductases, are involved in fatty acid synthesis. The
      reaction entails NADPH/NADH-mediated conversion of beta-oxoacyl-ACP (acyl-carrier
      protein) into beta-hydroxyacyl-ACP. HMwFabGs (high-molecular-weight FabG) form a
      phylogenetically separate group of FabG enzymes. FabG4, an HMwFabG from
      Mycobacterium tuberculosis, contains two distinct domains, an N-terminal
      'flavodoxintype' domain and a C-terminal oxoreductase domain. The catalytically
      active C-terminal domain utilizes NADH to reduce beta-oxoacyl-CoA to beta
      hydroxyacyl-CoA. In the present study the crystal structures of the FabG4-NADH
      binary complex and the FabG4-NAD+-hexanoyl-CoA ternary complex have been
      determined to understand the substrate specificity and catalytic mechanism of
      FabG4. This is the first report to demonstrate how FabG4 interacts with its
      coenzyme NADH and hexanoyl-CoA that mimics an elongating fattyacyl chain
      covalently linked with CoA. Structural analysis shows that the binding of
      hexanoyl-CoA within the active site cavity of FabG significantly differs from
      that of the C16 fattyacyl substrate bound to mycobacterial FabI [InhA (enoyl-ACP
      reductase)]. The ternary complex reveals that both loop I and loop II interact
      with the phosphopantetheine moiety of CoA or ACP to align the covalently linked
      fattyacyl substrate near the active site. Structural data ACP inhibition studies
      indicate that FabG4 can accept both CoA- and ACP-based fattyacyl substrates. We
      have also shown that in the FabG4 dimer Arg146 and Arg445 of one monomer interact
      with the C-terminus of the second monomer to play pivotal role in substrate
      association and catalysis.

PMID- 23163772
TI  - Semantic development in Spanish-English bilingual children: effects of age and
      language experience.
AB  - This study examines semantic development in 60 Spanish-English bilingual
      children, ages 7 years 3 months to 9 years 11 months, who differed orthogonally
      in age (younger, older) and language experience (higher English experience [HEE],
      higher Spanish experience [HSE]). Children produced 3 associations to 12 pairs of
      translation equivalents. Older children produced more semantic responses and code
      switched more often from Spanish to English than younger children. Within each
      group, children demonstrated better performance in the more frequently used than
      the less used language. The HEE children outperformed the HSE children in English
      and the HSE children outperformed the HEE children in Spanish. These effects of
      age and language experience are consistent with predictions of the revised
      hierarchical model of bilingual lexical organization.

PMID- 23163773
TI  - Evaluation of the impact of uveitis on visual-related quality of life.
AB  - PURPOSE: To determine quality of life in patients with uveitis and investigate
      the association between clinical parameters of uveitis and visual functioning.
      METHODS: Prospective cross-sectional study. The interviewer- administered
      National Eye Institute visual function questionnaire (VFQ-25) was used in 117
      adult outpatient uveitic patients. Their scores were compared against 48 controls
      with no ocular history. Subgroup differences amongst the patients were compared
      using Mann-Whitney and Kruskal-Wallis test. Multiple regression analysis was
      performed to determine the associations of visual function and disease
      characteristics of uveitis. RESULTS: VFQ-25 composite scores for patients were
      significantly lower than controls in all domains except driving. In multivariable
      analysis, lower VFQ-25 composite scores were associated with a chronic course of
      disease, even after taking into account the influences of visual acuity,
      treatment regimes and location of disease. CONCLUSIONS: Uveitic patients reported
      poorer visual functioning. A chronic course of disease is associated with poorer
      functioning.

PMID- 23163774
TI  - Adaptation and clonal selection models of castration-resistant prostate cancer:
      current perspective.
AB  - Prostate cancer is a leading cause of cancer deaths in men worldwide. Management
      of the disease has remained a great challenge and even more so is the aggressive
      advanced stage with castration-resistant behavior. The mechanisms and timing of
      development of castration-resistant prostate cancer are unclear and remain
      debatable. Progression to castration-resistant prostate cancer is undoubtedly
      multifactorial, with a number of molecular-genetic aberrations implicated.
      However, a key question that remains unanswered is: when in the evolution of
      prostate cancer do the changes that confer castration resistance occur? Earlier
      attempts to address this question led to two proposed models: the "adaptation"
      and the "clonal selection" models. Although the prevailing hypothesis is the
      adaptation model, there is recent evidence in favor of the clonal selection
      model. Clarification of the model development of castration-resistant prostate
      cancer might significantly alter our diagnostic and therapeutic strategies, and
      potentially lead to improved outcome of management of this daunting condition.
      Here we review existing knowledge and current research findings addressing the
      timing of events in the course of prostate cancer progression to castration
      resistant prostate cancer.

PMID- 23163775
TI  - A naked-eye on-off-on molecular "light switch" based on a reversible
      "conformational switch" of G-quadruplex DNA.
AB  - Herein, we report a new strategy for developing an on-off-on molecular "light
      switch" by utilizing the pH value to control the "conformational switch" of G
      quadruplex DNA. A novel ruthenium(II) complex with an emission enhancement factor
      of 150 was synthesized and introduced to detect the switch by the naked eye. The
      "light switch" can be repeatedly cycled off and on through the addition of H(+)
      and OH(-), respectively. The conformational transitions of G-quadruplex DNA in
      K(+) solution at different pH values in the acidic region were evidenced by
      circular dichroism and fluorescence titrations. Computational calculations by
      applying density functional theory (DFT)/time-dependent DFT and molecular docking
      were also carried out to gain insight into the "light-switch" mechanism.

PMID- 23163776
TI  - Photoreversible switching of the lower critical solution temperature in a
      photoresponsive host-guest system of pillar[6]arene with triethylene oxide
      substituents and an azobenzene derivative.
AB  - A new water-soluble thermoresponsive pillar[6]arene with triethylene oxide groups
      was synthesized. The pillar[6]arene showed lower critical solution temperature
      behavior in aqueous solution. Its clouding point was photoreversibly switched
      based on a photoresponsive host-guest system. The trans form of an azobenzene
      guest formed a stable 1:1 complex with the pillar[6]arene. Complexation increased
      the clouding point. Irradiation with UV light induced a conformation change for
      the azobenzene guest from the trans to cis form, and dethreading occurred because
      of a size mismatch between the cis form and the pillar[6]arene cavity. This
      dethreading decreased the clouding point. The photoresponsive host-guest system
      was reversible, and the clouding point could be switched by alternating
      irradiation with UV or visible light. We demonstrated photoresponsive reversible
      clear-to-turbid and turbid-to-clear transitions for the solution based on the
      reversible switching of the clouding point using the photosensitive host-guest
      system.

PMID- 23163777
TI  - Visual narrative structure.
AB  - Narratives are an integral part of human expression. In the graphic form, they
      range from cave paintings to Egyptian hieroglyphics, from the Bayeux Tapestry to
      modern day comic books (Kunzle, 1973; McCloud, 1993). Yet not much research has
      addressed the structure and comprehension of narrative images, for example, how
      do people create meaning out of sequential images? This piece helps fill the gap
      by presenting a theory of Narrative Grammar. We describe the basic narrative
      categories and their relationship to a canonical narrative arc, followed by a
      discussion of complex structures that extend beyond the canonical schema. This
      demands that the canonical arc be reconsidered as a generative schema whereby any
      narrative category can be expanded into a node in a tree structure. Narrative
      "pacing" is interpreted as a reflection of various patterns of this embedding:
      conjunction, left-branching trees, center-embedded constituencies, and others.
      Following this, diagnostic methods are proposed for testing narrative categories
      and constituency. Finally, we outline the applicability of this theory beyond
      sequential images, such as to film and verbal discourse, and compare this theory
      with previous approaches to narrative and discourse.

PMID- 23163778
TI  - The development of a family intervention competency assessment and reflection
      scale (FICARS) for psychosis.
AB  - Family intervention (FI) for psychosis has a robust evidence base. In
      recommending its use the revised NICE schizophrenia guideline states 'Healthcare
      professionals providing psychological interventions should have an appropriate
      level of competence'. Yet, no definitive instrument exists to outline what
      competences are required during and post FI training or help recruit staff with
      the appropriate knowledge and skill. This paper reports on the development of a
      Family Intervention competency assessment and reflection scale (FICARS). Using a
      systematic three-staged approach commonly used in health outcomes measurement
      development, a comprehensive literature review on UK-based FI training and
      commonly used assessment tools was undertaken. A FICARS draft was then
      constructed and revised in consultation with expert FI clinicians. Finally, a
      content validity study with FI trainers and students across three FI training
      programmes was undertaken to optimize FICARS aim to promote reflective assessment
      and professional development in FI skills and practice.

PMID- 23163779
TI  - On handling ephemeral resource constraints in evolutionary search.
AB  - We consider optimization problems where the set of solutions available for
      evaluation at any given time t during optimization is some subset of the feasible
      space. This model is appropriate to describe many closed-loop optimization
      settings (i.e., where physical processes or experiments are used to evaluate
      solutions) where, due to resource limitations, it may be impossible to evaluate
      particular solutions at particular times (despite the solutions being part of the
      feasible space). We call the constraints determining which solutions are non
      evaluable ephemeral resource constraints (ERCs). In this paper, we investigate
      two specific types of ERC: one encodes periodic resource availabilities, the
      other models commitment constraints that make the evaluable part of the space a
      function of earlier evaluations conducted. In an experimental study, both types
      of constraint are seen to impact the performance of an evolutionary algorithm
      significantly. To deal with the effects of the ERCs, we propose and test five
      different constraint-handling policies (adapted from those used to handle
      standard constraints), using a number of different test functions including a
      fitness landscape from a real closed-loop problem. We show that knowing
      information about the type of resource constraint in advance may be sufficient to
      select an effective policy for dealing with it, even when advance knowledge of
      the fitness landscape is limited. 

PMID- 23163780
TI  - Fitness function distributions over generalized search neighborhoods in the q-ary
      hypercube.
AB  - The frequency distribution of a fitness function over regions of its domain is an
      important quantity for understanding the behavior of algorithms that employ
      randomized sampling to search the function. In general, exactly characterizing
      this distribution is at least as hard as the search problem, since the solutions
      typically live in the tails of the distribution. However, in some cases it is
      possible to efficiently retrieve a collection of quantities (called moments) that
      describe the distribution. In this paper, we consider functions of bounded
      epistasis that are defined over length-n strings from a finite alphabet of
      cardinality q. Many problems in combinatorial optimization can be specified as
      search problems over functions of this type. Employing Fourier analysis of
      functions over finite groups, we derive an efficient method for computing the
      exact moments of the frequency distribution of fitness functions over Hamming
      regions of the q-ary hypercube. We then use this approach to derive equations
      that describe the expected fitness of the offspring of any point undergoing
      uniform mutation. The results we present provide insight into the statistical
      structure of the fitness function for a number of combinatorial problems. For the
      graph coloring problem, we apply our results to efficiently compute the average
      number of constraint violations that lie within a certain number of steps of any
      coloring. We derive an expression for the mutation rate that maximizes the
      expected fitness of an offspring at each fitness level. We also apply the results
      to the slightly more complex frequency assignment problem, a relevant application
      in the domain of the telecommunications industry. As with the graph coloring
      problem, we provide formulas for the average value of the fitness function in
      Hamming regions around a solution and the expectation-optimal mutation rate. 

PMID- 23163781
TI  - Shape-controlled synthesis of Pd nanocrystals and their catalytic applications.
AB  - Palladium is a marvelous catalyst for a rich variety of reactions in industrial
      processes and commercial devices. Most Pd-catalyzed reactions exhibit structure
      sensitivity, meaning that the activity or selectivity depends on the arrangement
      of atoms on the surface. Previously, such reactions could only be studied in
      ultrahigh vacuum using Pd single crystals cut with a specific crystallographic
      plane. However, these model catalysts are far different from real catalytic
      systems owing to the absence of atoms at corners and edges and the extremely
      small specific surface areas for the model systems. Indeed, enhancing the
      performance of a Pd-based catalyst, in part to reduce the amount needed of this
      precious and rare metal for a given reaction, requires the use of Pd with the
      highest possible specific surface area. Recent advances in nanocrystal synthesis
      are offering a great opportunity to investigate and quantify the structural
      sensitivity of catalysts based on Pd and other metals. For a structure-sensitive
      reaction, the catalytic properties of Pd nanocrystals are strongly dependent on
      both the size and shape. The shape plays a more significant role in controlling
      activity and selectivity, because the shape controls not only the facets but also
      the proportions of surface atoms at corners, edges, and planes, which affect the
      outcomes of possible reactions. We expect catalysts based on Pd nanocrystals with
      optimized shapes to meet the increasing demands of industrial applications at
      reduced loadings and costs. In this Account, we discuss recent advances in the
      synthesis of Pd nanocrystals with controlled shapes and their resulting
      performance as catalysts for a large number of reactions. First, we review
      various synthetic strategies based on oxidative etching, surface capping, and
      kinetic control that have been used to direct the shapes of nanocrystals. When
      crystal growth is under thermodynamic control, the capping agent plays a pivotal
      role in determining the shape of a product by altering the order of surface
      energies for different facets through selective adsorption; the resulting product
      has the lowest possible total surface energy. In contrast, the product of a
      kinetically controlled synthesis often deviates from the thermodynamically
      favored structure, with notable examples including nanocrystals enclosed by high
      index facets or concave surfaces. We then discuss the key parameters that control
      the nucleation and growth of Pd nanocrystals to decipher potential growth
      mechanisms and build a connection between the experimental conditions and the
      pathways to different shapes. Finally, we present a number of examples to
      highlight the use of these Pd nanocrystals as catalysts or electrocatalysts for
      various applications with structure-sensitive properties. We believe that a deep
      understanding of the shape-dependent catalytic properties, together with an
      ability to experimentally maneuver the shape of metal nanocrystals, will
      eventually lead to rational design of advanced catalysts with substantially
      enhanced performance. 

PMID- 23163782
TI  - Investigation of silicon-based nanostructure morphology and chemical termination
      on laser desorption ionization mass spectrometry performance.
AB  - We have evaluated the laser desorption ionization mass spectrometry (LDI-MS)
      performance of six nanostructured silicon surfaces of different morphologies and
      chemical functionalizations. The substrates have been synthesized either by metal
      assisted etching method or by vapor-liquid-solid (VLS) growth technique. In
      addition to the commercial nanostructured silicon-based surface (NALDI) target
      plates, serving as reference, the homemade surfaces have been evaluated in mass
      spectrometry experiments conducted with peptide solutions mimicking tryptic
      digests. LDI surfaces synthesized by metal-assisted etching method were the most
      efficient in terms of signal intensities and number of detected peptides. The
      surface providing the best LDI-MS performance was composed of two nanostructured
      layers. Interestingly, we also observed a significant influence of the type of
      organic coating (hydrocarbon vs fluorocarbon) on peptide ionization
      discrimination.

PMID- 23163783
TI  - Epigallocatechin gallate induce cell death and apoptosis in triple negative
      breast cancer cells Hs578T.
AB  - In the present work, we investigated the effect of epigallocatechin gallate
      (EGCG) on triple negative breast cancer cells (Hs578T) to reduce cell
      proliferation and to evaluate early apoptotic signals. The dynamic monitoring of
      Hs578T cells treated with EGCG using the xCELLigence System confirm the
      antiproliferative effects obtained by MTT test. EGCG induced significant
      increases in apoptosis at 48 and 72 h after treatment by activation of cell death
      pathways and apoptosis at mRNA level. Significant gene expression differences
      were observed for 22 genes, of which 18 were upregulated and four downregulated
      were identified. EGCG altered the expression of several antiapoptotic genes,
      while increasing the expression of other genes. The limited success may be due to
      the activation of the antiapoptotic genes BAG3, XIAP, RIPK2, which may be
      associated with resistance to cancer treatment.

PMID- 23163784
TI  - Editorial comment to Outcome of small intestinal submucosa graft for repair of
      anterior urethral strictures.

PMID- 23163785
TI  - Binomial probability distribution model-based protein identification algorithm
      for tandem mass spectrometry utilizing peak intensity information.
AB  - Mass spectrometry has become one of the most important technologies in proteomic
      analysis. Tandem mass spectrometry (LC-MS/MS) is a major tool for the analysis of
      peptide mixtures from protein samples. The key step of MS data processing is the
      identification of peptides from experimental spectra by searching public sequence
      databases. Although a number of algorithms to identify peptides from MS/MS data
      have been already proposed, e.g. Sequest, OMSSA, X!Tandem, Mascot, etc., they are
      mainly based on statistical models considering only peak-matches between
      experimental and theoretical spectra, but not peak intensity information.
      Moreover, different algorithms gave different results from the same MS data,
      implying their probable incompleteness and questionable reproducibility. We
      developed a novel peptide identification algorithm, ProVerB, based on a binomial
      probability distribution model of protein tandem mass spectrometry combined with
      a new scoring function, making full use of peak intensity information and, thus,
      enhancing the ability of identification. Compared with Mascot, Sequest, and SQID,
      ProVerB identified significantly more peptides from LC-MS/MS data sets than the
      current algorithms at 1% False Discovery Rate (FDR) and provided more confident
      peptide identifications. ProVerB is also compatible with various platforms and
      experimental data sets, showing its robustness and versatility. The open-source
      program ProVerB is available at 
      http://bioinformatics.jnu.edu.cn/software/proverb/ .

PMID- 23163786
TI  - Contingent attentional capture by conceptually relevant images.
AB  - Attentional capture is an unintentional shift of visuospatial attention to the
      location of a distractor that is either highly salient, or relevant to the
      current task set. The latter situation is referred to as contingent capture, in
      that the effect is contingent on a match between characteristics of the stimuli
      and the task-defined attentional-control settings of the viewer. Contingent
      capture has been demonstrated for low-level features, such as color, motion, and
      orientation. In the present paper we show that contingent capture can also occur
      for conceptual information at the superordinate level (e.g., sports equipment,
      marine animal, dessert food). This effect occurs rapidly (i.e., within 200 ms),
      is a spatial form of attention, and is contingent on attentional-control settings
      that change on each trial, suggesting that natural images can be decoded into
      their conceptual meaning to drive shifts of attention within the time course of a
      single fixation.

PMID- 23163787
TI  - Being selective at the plate: processing dependence between perceptual variables
      relates to hitting goals and performance.
AB  - Performance of a skill that involves acting on a goal object (e.g., a ball to be
      hit) can influence one's judgment of the size and speed of that object. The
      present study examined how these action-specific effects are affected when the
      goal of the actor is varied and they are free to choose between alternative
      actions. In Experiment 1, expert baseball players were asked to perform three
      different directional hitting tasks in a batting simulation and make interleaved
      perceptual judgments about three ball parameters (speed, plate crossing location,
      and size). Perceived ball size was largest (and perceived speed was slowest) when
      the ball crossing location was optimal for the particular hitting task the batter
      was performing (e.g., an "outside" pitch for opposite-field hitting). The
      magnitude of processing dependency between variables (speed vs. location and size
      vs. location) was positively correlated with batting performance. In Experiment
      2, the action-specific effects observed in Experiment 1 were mimicked by
      systematically changing the ball diameter in the simulation as a function of
      plate crossing location. The number of swing initiations was greater when ball
      size was larger, and batters were more successful in the hitting task for which
      the larger pitches were optimal (e.g., greater number of pull hits than opposite
      field hits when "inside" pitches were larger). These findings suggest attentional
      accentuation of goal-relevant targets underlies action-related changes in
      perception and are consistent with an action selection role for these effects.

PMID- 23163788
TI  - Memory for found targets interferes with subsequent performance in multiple
      target visual search.
AB  - Multiple-target visual searches--when more than 1 target can appear in a given
      search display--are commonplace in radiology, airport security screening, and the
      military. Whereas 1 target is often found accurately, additional targets are more
      likely to be missed in multiple-target searches. To better understand this
      decrement in 2nd-target detection, here we examined 2 potential forms of
      interference that can arise from finding a 1st target: interference from the
      perceptual salience of the 1st target (a now highly relevant distractor in a
      known location) and interference from a newly created memory representation for
      the 1st target. Here, we found that removing found targets from the display or
      making them salient and easily segregated color singletons improved subsequent
      search accuracy. However, replacing found targets with random distractor items
      did not improve subsequent search accuracy. Removing and highlighting found
      targets likely reduced both a target's visual salience and its memory load,
      whereas replacing a target removed its visual salience but not its representation
      in memory. Collectively, the current experiments suggest that the working memory
      load of a found target has a larger effect on subsequent search accuracy than
      does its perceptual salience.

PMID- 23163789
TI  - On the electrophysiological evidence for the capture of visual attention.
AB  - The presence of a salient distractor interferes with visual search. According to
      the salience-driven selection hypothesis, this interference is because of an
      initial deployment of attention to the distractor. Three event-related potential
      (ERP) findings have been regarded as evidence for this hypothesis: (a) salient
      distractors were found to elicit an ERP component called N2pc, which reflects
      attentional selection; (b) with target and distractor on opposite sides, a
      distractor N2pc was reported to precede the target N2pc (N2pc flip); (c) the
      distractor N2pc on slow-response trials was reported to occur particularly early,
      suggesting that the fastest shifts of attention were driven by salience. This
      evidence is equivocal, however, because the ERPs were noisy (b, c) and were
      averaged across all trials, thereby making it difficult to know whether attention
      was deployed directly to the target on some trials (a, b). We reevaluated this
      evidence using a larger sample size to reduce noise and by analyzing ERPs
      separately for fast- and slow-response trials. On fast-response trials, the
      distractor elicited a contralateral positivity (PD)-an index of attentional
      suppression-instead of an N2pc. There was no N2pc flip or early distractor N2pc.
      As it stands, then, there is no ERP evidence for the salience-driven selection
      hypothesis.

PMID- 23163790
TI  - Multisensory uncertainty reduction for hand localization in children and adults.
AB  - Adults can integrate multiple sensory estimates to reduce their uncertainty in
      perceptual and motor tasks. In recent studies, children did not show this ability
      until after 8 years. Here we investigated development of the ability to integrate
      vision with proprioception to localize the hand. We tested 109 4- to 12-year-olds
      and adults on a simple pointing task. Participants used an unseen hand beneath a
      table to point to targets presented on top of the table to vision alone,
      proprioception alone, or both together. Overall, 7- to 9-year-olds' and adults'
      points were significantly less variable given vision and proprioception together
      compared with either alone. However, this variance reduction was present at all
      ages in the subset of participants whose proprioceptive estimates were less than
      two times more variable than their visual. These results, together with analyses
      of cue weighting, indicate that all groups integrated vision and proprioception,
      but only 7- to 9-year-olds and adults consistently selected cue weights that were
      appropriate to their own single-cue reliabilities. Cue weights used at 4-6 and 10
      12 years still allowed over half of participants at these ages to reduce their
      pointing variability. One explanation for poorer group-level cue weighting at 10
      12 years is that this ages represents a period of relatively rapid physical
      growth. An existing Bayesian model of hand localization did not describe either
      adults' or children's data well, but the results suggest future improvements to
      the model.

PMID- 23163791
TI  - Optimal weighting of costs and probabilities in a risky motor decision-making
      task requires experience.
AB  - Previous research has revealed that people choose to aim toward an "optimal"
      endpoint when faced with a movement task with externally imposed payoffs. This
      optimal endpoint is modeled based on the magnitude of the payoffs and the
      probability of hitting the different payoff regions (endpoint variability).
      Endpoint selection, however, has only been studied after people had experience
      with the aiming task. The present study examined initial endpoint selection and
      how it changed as a function of experience with performing the task. Participants
      completed 300 movements to a target that was overlapped by a penalty region. Mean
      endpoint was analyzed in intervals of 50 trials. Predictions based on the optimal
      model would indicate that the mean endpoint should be farther from the penalty
      region early in practice when endpoint variability is higher-increasing target
      misses but decreasing costly penalty hits. As variability decreases, however, it
      is predicted that the endpoint should shift closer to the optimal location. In
      contrast to these predictions, participants' mean movement endpoints started
      closer to the penalty region and shifted away with increasing practice, even as
      endpoint variability decreased. This pattern of endpoint selection leads to
      suboptimal gains early in experience but more optimal gains by the end of the
      trials. These findings suggest that, similar to results found in cognitive
      decision-making tasks, people need to receive performance-based feedback to
      weight their estimations of probability and payoffs in motor tasks.

PMID- 23163792
TI  - The effects of thoughts of survival and thoughts of death on recall in the
      adaptive memory paradigm.
AB  - In a recent paper Hart and Burns (2012) presented evidence that conditions that
      prime thoughts of one's mortality benefit recall. Drawing on the conceptual
      relation between thoughts of death and thoughts of survival, Hart and Burns
      interpret their findings as suggestive of the possibility that death-related
      thoughts function in manner similar to survival-related thoughts in enhancing
      recall. In the present study I draw on evolutionary arguments to question whether
      a conceptual relation between thoughts of death and thoughts of survival
      translates into a functional relation. I then present data showing that while
      death-related thoughts can promote high levels of recall, (a) the level achieved
      does not match that produced by survival processing and (b) survival and death
      cognition likely rely on different mechanisms to achieve their effects. 

PMID- 23163793
TI  - Mediterranean diet- and exercise-induced improvement in age-dependent vascular
      activity.
AB  - The aging effect on microvascular integrity, marked by endothelial dysfunction
      and reduction in exercise tolerance, is a major cause of CVD (cardiovascular
      disease). Improved dietary habits, known to reduce morbidity and mortality, are
      also known to attenuate those aging effects. The present study investigated the
      effects of combined MD (Mediterranean diet) and exercise intervention on lower-
      and upper-limb cutaneous microvascular functions in an older healthy population.
      A total of 22 sedentary healthy participants (age, 55+/-4 years) underwent
      cardiopulmonary exercise tolerance test, and were assessed for their upper- and
      lower-limb vascular endothelial CVC (cutaneous vascular conductance) using LDF
      (laser Doppler fluximetry) with endothelium-dependent [ACh (acetylcholine
      chloride)] and -independent [SNP (sodium nitroprusside)] vasodilation.
      Participants were then randomized into two groups: MD and non-MD, and followed an
      8-week intervention programme, which included discontinuous treadmill running
      based on each individual's exertion, twice per week. Exercise training improved
      CVC in both groups (e.g. 0.42+/-0.19 compared with 1.50+/-1.05 and 0.47+/-0.26
      compared with 1.15+/-0.59 at 1000 MUCb for MD and non-MD respectively; P<0.001).
      This was also combined by improvement in the exercise tolerance indicated by
      increased VT (ventilatory threshold) in both groups [12.2+/-2.8 compared with
      14.8+/-2.8 ml.(kg of body weight)(-1).min(-1) and 11.7+/-2.7 compared with 14.6+/
      3.2 ml.(kg of body weight)(-1).min(-1) for MD and non-MD groups respectively;
      P<0.05]. However, the MD group showed greater improvement in endothelium
      dependent vasodilation than non-MD [ANCOVA (analyses of co-variance), P=0.02].
      The results of the present study suggest that compliance with MD, combined with
      regular moderate exercise, improves age-provoked microcirculatory endothelial
      dysfunction and increases exercise tolerance, both responsible for reducing
      cardiovascular risk in this age group.

PMID- 23163794
TI  - Azygous anterior cerebral artery and associated aneurysms: detection and
      identification using 3-dimensional time-of-flight magnetic resonance angiography.
AB  - AIM: The azygous anterior cerebral artery (Az) is a rarely observed anomaly of
      the anterior cerebral artery, and its associated aneurysm is even rarer. Our aim
      was to evaluate 3-dimensional time-of-flight magnetic resonance angiography (3-D
      TOF MRA) in the diagnosis of Az and associated aneurysms. MATERIALS AND METHODS:
      Three thousand five hundred seventy-two consecutive patients underwent 3-D-TOF
      MRA at 3.0 T. Postprocessing techniques, including volume rendering (VR) and
      single artery highlighting, were performed by a 3-D specialist. All MRA data and
      clinical information were recorded and stored in a database for further analysis.
      RESULTS: Fourteen patients (.39%) were identified as having an Az. Among these
      cases, 3 males (21.43%) had an aneurysm located at the distal bifurcation of the
      Az, with a mean size of 9.43 +/- 3.33 mm. In MRA, the common trunk of the Az was
      slightly larger in diameter than the A1 segment (2.62 +/- .35 mm vs. 2.54 +/- .35
      mm; P = .008). CONCLUSIONS: With the VR technique, 3-D-TOF MRA is feasible and
      valuable in detecting an Az and associated aneurysm. Our MRA-based study has
      proved that the Az is a rare anomaly but has a relatively high incidence of
      associated aneurysms.

PMID- 23163795
TI  - Maladaptive sex ratio adjustment by a sex-changing shrimp in selective-fishing
      environments.
AB  - 1. Selective harvesting is acknowledged as a serious concern in efforts to
      conserve wild animal populations. In fisheries, most studies have focused on
      gradual and directional changes in the life-history traits of target species.
      While such changes represent the ultimate response of harvested animals, it is
      also well known that the life history of target species plastically alters with
      harvesting. However, research on the adaptive significance of these types of
      condition-dependent changes has been limited. 2. We explored the adaptive
      significance of annual changes in the age at sex-change of the protandrous (male
      first) hermaphroditic shrimp and examined how selective harvesting affects life
      history variation, by conducting field observations across 13 years and a
      controlled laboratory experiment. In addition, we considered whether plastic
      responses by the shrimp would be favourable, negligible or negative with respect
      to the conservation of fishery resources. 3. The age at sex-change and the
      population structure of the shrimp fluctuated between years during the study
      period. The results of the field observations and laboratory experiment both
      indicated that the shrimp could plastically change the timing of sex-change in
      accordance with the age structure of the population. These findings provide the
      first concrete evidence of adult sex ratio adjustment by pandalid shrimp, a group
      that has been treated as a model in the sex allocation theory. 4. The sex ratio
      adjustment by the shrimp did not always seem to be sufficient, however, as the
      supplement of females is restricted by their annual somatic growth rate. In
      addition, adjusted sex ratios are further skewed by the unintentional female
      selectivity of fishing activity prior to the breeding season, indicating that the
      occurrence of males that have postponed sex-change causes sex ratio adjustment to
      become unfavourable. 5. We conclude that the plastic responses of harvested
      animals in selective fishing environments must be considered in efforts to
      conserve wild animal resources, because such responses can become maladaptive.

PMID- 23163796
TI  - Perspectives of clinical genetics professionals toward genome sequencing and
      incidental findings: a survey study.
AB  - The introduction of clinical genome-wide sequencing raises complex issues
      regarding the management of incidental findings. However, there is a lack of
      empirical studies assessing views of providers involved in potential disclosure
      of such findings. In an anonymous survey of 279 clinical genetics professionals,
      we found that the vast majority of participants agreed that they were interested
      in knowing about clinically actionable incidental findings in themselves (96%)
      and their child (99%), and they reported that these types of findings should be
      disclosed in adult (96%) and minor (98%) patients. Approximately three-fourths
      agreed that they were personally interested in knowing about an adult-onset
      clinically actionable disease (78%) and a childhood-onset non-clinically
      actionable disease (75%) in their child. A similar percentage of participants
      (70%) felt that these two types of findings should be disclosed to patients.
      Forty-four percent of participants wanted to know about an incidental finding
      that indicates an adult-onset non-clinically actionable condition in themselves
      and 31% wanted to know about this type of information in their child. Findings
      from this study revealed participants' views highly dependent on clinical
      actionability. Further research is needed with a broader population of
      geneticists to increase generalizability, and with diverse patients to assess
      their perspectives about results disclosure from clinical sequencing. 

PMID- 23163797
TI  - Pathways to adolescent internalizing: early attachment insecurity as a lasting
      source of vulnerability.
AB  - Despite theoretical links between attachment quality in early childhood and
      subsequent internalizing symptoms, there is limited empirical evidence supporting
      direct effects. In this article, we test whether early attachment insecurity
      indirectly contributes to adolescent internalizing by increasing the likelihood
      of certain pathways leading to elevated symptoms (i.e., moderated mediation).
      Structural equation modeling and bootstrapping were used to test for moderated
      mediation using longitudinal data from 910 adolescents participating in the
      National Institute of Child Health and Human Development Study of Early Child
      Care (M age = 15.1; 50% female, 23% racial/ethnic minority). Among dyads with a
      history of an insecure attachment in early childhood, mothers' negative emotions
      during the transition to adolescence significantly predicted less availability
      during parent-adolescent interactions, which in turn increased adolescents'
      preoccupation with parental relationships. The same process was not evident in
      youth with a history of secure attachments. However, the extent to which
      preoccupation with parental relationships was associated with increases in
      internalizing symptoms depended on both attachment history and gender. Results
      highlight one pathway by which early attachment history may indirectly contribute
      to increased internalizing symptoms for girls during the transition to
      adolescence.

PMID- 23163798
TI  - Bartonella henselae trimeric autotransporter adhesin BadA expression interferes
      with effector translocation by the VirB/D4 type IV secretion system.
AB  - The Gram-negative, zoonotic pathogen Bartonella henselae is the aetiological
      agent of cat scratch disease, bacillary angiomatosis and peliosis hepatis in
      humans. Two pathogenicity factors of B. henselae - each displaying multiple
      functions in host cell interaction - have been characterized in greater detail:
      the trimeric autotransporter Bartonella adhesin A (BadA) and the type IV
      secretion system VirB/D4 (VirB/D4 T4SS). BadA mediates, e.g. binding to
      fibronectin (Fn), adherence to endothelial cells (ECs) and secretion of vascular
      endothelial growth factor (VEGF). VirB/D4 translocates several Bartonella
      effector proteins (Beps) into the cytoplasm of infected ECs, resulting, e.g. in
      uptake of bacterial aggregates via the invasome structure, inhibition of
      apoptosis and activation of a proangiogenic phenotype. Despite this knowledge of
      the individual activities of BadA or VirB/D4 it is unknown whether these major
      virulence factors affect each other in their specific activities. In this study,
      expression and function of BadA and VirB/D4 were analysed in a variety of
      clinical B. henselae isolates. Data revealed that most isolates have lost
      expression of either BadA or VirB/D4 during in vitro passages. However, the
      phenotypic effects of coexpression of both virulence factors was studied in one
      clinical isolate that was found to stably coexpress BadA and VirB/D4, as well as
      by ectopic expression of BadA in a strain expressing VirB/D4 but not BadA. BadA,
      which forms a dense layer on the bacterial surface, negatively affected VirB/D4
      dependent Bep translocation and invasome formation by likely preventing close
      contact between the bacterial cell envelope and the host cell membrane. In
      contrast, BadA-dependent Fn binding, adhesion to ECs and VEGF secretion were not
      affected by a functional VirB/D4 T4SS. The obtained data imply that the essential
      virulence factors BadA and VirB/D4 are likely differentially expressed during
      different stages of the infection cycle of Bartonella.

PMID- 23163799
TI  - Gene therapy for noninfectious uveitis.
AB  - Noninfectious intraocular inflammatory disease remains a significant cause of
      visual loss, even with current systemic immunosuppression. Alternative novel
      treatments are thus required, particularly for severe forms of posterior uveitis.
      Encouraging results from several phase I/II clinical trials of gene therapy for
      monogenic retinal disorders have paved the way for the development of this
      approach for other ocular conditions. Gene therapy for uveitis offers the
      possibility of potent, self-regulating, long-term disease control following a
      single treatment and without systemic side effects. To date, gene therapy
      approaches using interleukin-10, interleukin-1 receptor antagonist, interferon
      alpha, soluble TNF-alpha receptors, and alpha-MSH gene transfer have been used
      successfully to attenuate experimental animal models of uveitis. This review
      evaluates these preclinical studies, considers the route to clinical application,
      and explores future targets and approaches.

PMID- 23163800
TI  - Influence of different materials on the concentration of delousing agents in sea
      water during bioassays.

PMID- 23163802
TI  - A general organocatalytic approach toward the enantioselective total synthesis of
      indolizidine based alkaloids.
AB  - Four indolizidine based alkaloids (IBAs) have been synthesized in a highly
      enantioselective, straightforward, and flexible manner. As a key step our
      previously developed Bronsted acid catalyzed vinylogous Mannich reaction was
      employed which easily afforded gram amounts of an optically pure central
      intermediate which can be converted into a wide range of diversely substituted
      IBAs.

PMID- 23163803
TI  - Phosphorus-nitrogen compounds. Part 24. Syntheses, crystal structures,
      spectroscopic and stereogenic properties, biological activities, and DNA
      interactions of novel spiro-ansa-spiro- and ansa-spiro-ansa
      cyclotetraphosphazenes.
AB  - The reactions of octachlorocyclotetraphosphazene, N(4)P(4)Cl(8), with N(2)O(2)
      donor-type aminopodands (1a, 1b, 1g, and 1h) afforded two kinds of derivatives,
      namely, spiro-ansa-spiro (sas) (2a, 2b, 2g, and 2h) and ansa-spiro-ansa (asa) (3a
      and 3b) phosphazenes. The partly substituted sas phosphazenes (2a and 2b) reacted
      with excess pyrrolidine and morpholine in tetrahydrofuran to produce the
      tetrapyrrolidino (2c and 2d) and morpholino (2e and 2f) derivatives. The
      reactions of the asa phosphazenes (3a and 3b) with excess pyrrolidine and
      morpholine produced gem-2-trans-6-dichloropyrrolidinophosphazenes (3c and 3d) and
      -morpholinophosphazenes (3e and 3f). However, the fully substituted products were
      not obtained in these solvents. In addition, the expected fully substituted
      compound was not obtained from the reaction of 3a with excess pyrrolidine by
      standard or microwave-assisted methods. The reaction of the long-chain starting
      compound (1g) with N(4)P(4)Cl(8) gave sas (2g) and the interesting 2,6-ansa-spiro
      bicyclo product (bicyclo-2,6-as; 4g), while the reaction of 1h with N(4)P(4)Cl(8)
      yielded only sas (2h). The structural investigations of the compounds were
      verified by elemental analyses, mass spectrometry, Fourier transform infrared,
      and DEPT, HSQC, HMBC, (1)H, (13)C, and (31)P NMR techniques. The crystal
      structures of 2b, 3a, 3b, 3e, and 4g were determined by X-ray crystallography.
      Compounds 2a-2h, 3a-3f, and 4g had two stereogenic P atoms. Compound 3b had one
      enantiomer according to the Flack parameter, and 3f was a racemic mixture, as
      shown by chiral high-performance liquid chromatography and chiral-solvating
      agent, (R)-(+)-2,2,2-trifluoro-1-(9'-anthryl)ethanol, experiments. Furthermore,
      compounds 2a, 2c, and 2d exhibited weak antibacterial activity against (G+)
      bacterium, and 3c and 3d displayed moderate antifungal activity against Candida
      tropicalis. Gel electrophoresis data demonstrated that 2e, 3c, and 3e promoted
      the formation of DNA cleavage. The prevention of BamHI digestion by 2a-2f and 3a
      3f, except 2b and 2e, disclosed binding with GG nucleotides in DNA.

PMID- 23163801
TI  - New models of Tetrahymena telomerase RNA from experimentally derived constraints
      and modeling.
AB  - The telomerase ribonucleoprotein complex ensures complete replication of
      eukaryotic chromosomes. Telomerase RNA (TER) provides the template for
      replicating the G-rich strand of telomeric DNA, provides an anchor site for
      telomerase-associated proteins, and participates in catalysis through several
      incompletely characterized mechanisms. A major impediment toward understanding
      its nontemplating roles is the absence of high content structural information for
      TER within the telomerase complex. Here, we used selective 2'-hydroxyl acylation
      analyzed by primer extension (SHAPE) to examine the structure of Tetrahymena TER
      free in solution and bound to tTERT in the minimal telomerase RNP. We discovered
      a striking difference in the two conformations and established direct evidence
      for base triples in the tTER pseudoknot. We then used SHAPE data, previously
      published FRET data, and biochemical inference to model the structure of tTER
      using discrete molecular dynamics simulations. The resulting tTER structure was
      docked with a homology model of the Tetrahymena telomerase  reverse transcriptase
      (tTERT) to characterize the conformational changes of tTER telomerase assembly.
      Free in solution, tTER appears to contain four pairing regions: stems I, II, and
      IV, which are present in the commonly accepted structure, and stem III, a large
      paired region that encompasses the template and pseudoknot domains. Our
      interpretation of the data and subsequent modeling affords a molecular model for
      telomerase assemblage in which a large stem III of tTER unwinds to allow proper
      association of the template with the tTERT active site and formation of the
      pseudoknot. Additionally, analysis of our SHAPE data and previous enzymatic
      footprinting allow us to propose a model for stem-loop IV function in which tTERT
      is activated by binding stem IV in the major groove of the helix-capping loop.

PMID- 23163804
TI  - Staff and relatives' perspectives on the aggressive behaviour of older people
      with dementia in residential care: a qualitative study.
AB  - Staff and relative perspectives on patient aggression in dementia care units are
      seriously under researched in the U.K. Any work that has been conducted has
      relied upon quantitative studies. Qualitative research on aggression management
      in older peoples services are rare. In-depth views that can offer insights into
      causation and management strategies are therefore under represented in the
      literature. In order to investigate this issue further we interviewed a number of
      nursing staff and relatives in four U.K. care homes in the North West of England.
      Using a combined approach of one-to-one interviews (for staff) and focus groups
      (for relatives) we explored their views as to the reasons for and ways of
      responding to aggressive behaviour. This was part of a larger study reported upon
      elsewhere. Using thematic analysis we found similar results from both staff and
      relatives and as such their views were categorized into two broad areas:
      causation and management. In regards to causation we noted three sub-themes;
      internal, external and interpersonal factors which are further subdivided in the
      paper and for management two broad categories: the compassionate approach and
      'don't go in strong'. The results indicated that staff in the participating units
      embraced a person-centred approach to aggression management. They predominantly
      respond to aggressive incidents with interpersonal strategies, such as
      distraction as opposed to medication or restraint. Overall they adopt a person
      centre approach to patient care. Relatives were clear in their perceptions of
      aggression as an interpersonal challenge, which is compounded or mediated by the
      illness of dementia. Consequently they were positive in their views of staff
      using non-coercive interventions. While the results of this and our earlier study
      are promising suggesting a less invasive approach to this aspect of dementia
      care, given the limitations of a small sample, more research of a similar nature
      is warranted. Findings from multidimensional studies can then provide a sounder
      basis for health and social care education, and person centred informed practice
      to reduce the incidence of aggression through preventative strategies.

PMID- 23163805
TI  - Benchmarking of continuous black box optimization algorithms.

PMID- 23163806
TI  - Determination of types and binding sites of advanced glycation end products for
      substance P.
AB  - Glycation by endogenous dicarbonyl metabolites such as glyoxal is an important
      spontaneous post-translational (PTM) modification of peptides and proteins
      associated with structural and functional impairment. The aim of this study was
      to investigate types and site of PTM of glyoxal-derived advanced glycation end
      products-in the neuropeptide substance P by ultrahigh-resolution Fourier
      transform ion cyclotron resonance (FTICR), mass spectrometry, and tandem mass
      spectrometry (MS/MS) experiments. The main site of PTM by glyoxal was the side
      chain guanidine moiety of the arginine residue. Binding site identification has
      been achieved by electron capture dissociation, double-resonance electron capture
      dissociation, and collision-activated dissociation, with assignment of the
      modified amino acid residue with mass error <1 ppm.

PMID- 23163807
TI  - Angiogenesis-related microRNAs in colon cancer.
AB  - INTRODUCTION: Angiogenesis, for its fundamental role in cancer growth and
      metastasis, has become an appealing target in cancer therapy. A number of
      angiogenesis-related microRNAs (miRNAs) are under investigation and they can
      affect the cancerous phenotype of malignant cells. AREAS COVERED: The authors
      review the recent advances in angiogenesis-related miRNAs in human colon cancer.
      They also envisage future developments toward potential miRNA-based applications
      to cancer treatment. EXPERT OPINION: Angiogenesis-related miRNAs may reasonably
      be considered as a valuable cancer therapeutic tool. More investigations should
      be performed to promote therapeutic-clinical research of miRNAs in patients with
      colon cancer.

PMID- 23163808
TI  - Aromatic stacking interactions in flavin model systems.
AB  - Flavins feature multiple attributes that explain their widespread occurrence in
      nature, including photostability, reversible electrochemistry, and especially the
      tunability of their optical, electronic, and redox properties by supramolecular
      interactions and modification of their chemical structure. Flavins are important
      redox cofactors for enzymatic catalysis and are central to a wide variety of
      processes, including biosynthesis, electron transport, photosynthesis, and DNA
      repair. The wide range of processes catalyzed by flavins makes them promising
      leads for synthetic catalysts. Their properties are also relevant to organic
      electronic and optoelectronic devices, where they have the potential to serve as
      photoactive electron carriers, a very uncommon property in current photovoltaic
      systems. In flavoenzymes, the flavin cofactor binds to the active site of the
      apoenzyme through noncovalent interactions. These interactions regulate cofactor
      recognition and tune the redox behavior of the flavin cofactor. In this Account,
      we describe the creation of host-guest systems based on small molecule, polymer,
      and nanoparticle scaffolds that explore the role of aromatic stacking on the
      redox properties of the flavin and provide insight into flavoenzyme function. We
      also describe the creation of synthetic flavin-based interlocked structures
      featuring aromatic stacking interactions, along with the use of aromatic stacking
      to direct self-assembly of flavin-based materials. The interplay between redox
      events and aromatic stacking interactions seen in these synthetic models is
      important for fundamental understanding of biological systems including the
      flavoenzymes. The precise control of aromatic interactions and binding of flavins
      not only underpins their biological activity but gives them the potential to be
      developed into novel organic optoelectronic materials based on tuned synthetic
      flavin-receptor assemblies. In a broader context, the redox properties of the
      flavin provide a very concise tool for looking at the role of electronics in
      aromatic stacking, an issue of general importance in biological and
      supramolecular chemistry.

PMID- 23163809
TI  - Identification of potential biomarkers for ovarian cancer by urinary metabolomic
      profiling.
AB  - To evaluate the application of urinary metabolomics on discovering potential
      biomarkers for epithelial ovarian cancer (EOC), urine samples from 40
      preoperative EOC patients, 62 benign ovarian tumor (BOT) patients, and 54 healthy
      controls were collected and analyzed with ultraperformance liquid chromatography
      quadrupole time-of-flight mass spectrometry (UPLC-QTOF/MS). Good separations were
      obtained for EOC vs BOT, EOC vs healthy controls analyzed by partial least
      squares discriminant analysis, or principal component analysis. Twenty-two
      ascertained metabolomic biomarkers were found to be disturbed in several
      metabolic pathways among EOC patients, including nucleotide metabolism
      (pseudouridine, N4-acetylcytidine), histidine metabolism (L-histidine, imidazol-5
      yl-pyruvate), tryptophan metabolism (3-indolelactic acid), and mucin metabolism
      (3'-sialyllactose and 3-sialyl-N-acetyllactosamine). In addition, the
      concentrations of some urinary metabolites of 18 postoperative EOC patients among
      the 40 EOC patients changed significantly compared with those of their
      preoperative condition, and four of them suggested recovery tendency toward
      normal level after surgical operation, including N4-acetylcytidine,
      pseudouridine, urate-3-ribonucleoside, and succinic acid. These metabolites would
      be highly postulated to be associated with EOC. In conclusion, our study
      demonstrated that urinary metabolomics analysis by UPLC-QTOF/MS, performed in a
      minimally noninvasive and convenient manner, possessed great potential in
      biomarker discovery for EOC.

PMID- 23163811
TI  - Short communication: lamivudine plus a boosted-protease inhibitor as
      simplification strategy in HIV-infected patients: proof of concept.
AB  - There are scarce data about the use of a dual therapy with lamivudine plus a
      ritonavir-boosted protease inhibitor (PI/r) as simplification strategy. We
      performed a retrospective cohort study of 44 HIV-infected patients on suppressive
      triple therapy PI/r-based HAART, HBV negative, who discontinued one nucleoside
      analogue (NA) due to toxicity, and continued dual therapy with lamivudine plus
      the PI/r. The median time of HIV infection was 18.6 years, and CD4(+) count nadir
      was 150 cells/MUl (6-470). They had received a mean of four regimens before (2
      20), and 55% had a previous AIDS diagnosis. In eight cases, a previous resistance
      test showed two to seven secondary mutations in the protease gene, without
      resistance to the PI/r. The 184V mutation was not observed, but previous failure
      with a lamivudine-including regimen had been observed in four patients (9%). At
      baseline, patients had viral suppression (<50 copies/ml) for a median time of 794
      days (235-2344), while receiving atazanavir/r in five cases, lopinavir/r in 14,
      and darunavir/r in 25. They discontinued mainly tenofovir (19, 43%) and
      didanosine (15, 34%). During 101.5 patient-years of follow-up, only two patients
      failed (5%), because of incomplete adherence. CD4(+) count increase at 48 weeks
      was 55 cells/MUl. No new adverse events were observed, although total cholesterol
      and triglycerides increased significantly during the first 6 months after
      simplification. In conclusion, dual therapy with lamivudine plus a boosted PI was
      safe and effective as simplification strategy in patients with toxicity to NA.
      This combination could be an alternative to mono or triple therapy in hard-to
      treat patients.

PMID- 23163812
TI  - Derivation of transcranial Doppler criteria for angiographically proven middle
      cerebral artery vasospasm after aneurysmal subarachnoid hemorrhage.
AB  - BACKGROUND: Transcranial Doppler (TCD) has been subjected to criticism for
      detecting vasospasm (VSP). Our study's aim is to derive criteria for middle
      cerebral artery (MCA) vasospasm (MCA-VSP) based on cerebral angiography (CA).
      METHODS: A prospective data of patients with aneurysmal subarachnoid hemorrhage
      (aSAH) from January 2004 to August 2009. TCD was performed daily from day 2 to 14
      from symptom's onset. Follow-up CA was done at day 7-9. TCD mean flow velocities
      (MFV) of all vessels at baseline (b), middle (m) and before CA (preangio) were
      recorded. Several MCA MFV ratios were computed. Moderate to severe VSP on CA was
      defined as >1/3 luminal narrowing. Univariate and stepwise logistic regression
      analysis were performed. RESULTS: One hundred sixty-nine patients (338 MCA) with
      aSAH were included, mean age: 54.8 +/- 13, women: 103 (62%). Twenty-nine patients
      (8.6%) had angiographic MCA-VSP. TCD scoring system of 3 points for MCA-VSP was
      computed based on (a) bMCA MFV >= 120 cm/s (sensitivity: 59.3%, specificity: 85%,
      PPV: 36.4%, NPV: 93.5%, P < .001) (1 point), Preangio MCA MFV >= 150 cm/s (79.3%,
      89.9%, 39%, 97.3%, <.001) (1 point), and affected preangio MCA/bMCA MFV ratio >=
      1.5 (84%, 63%, 25.6%, 96.3%, .001) (1 point). The score of 3 has 96% sensitivity
      and 96% specificity (OR: 300) whereas the score of 1 has 12% sensitivity and 58%
      specificity (OR: 4.3) for identifying MCA-VSP. CONCLUSION: TCD stringent criteria
      for moderate to severe MCA-VSP are feasible and applicable in aSAH population.

PMID- 23163813
TI  - Elk herbivory alters small mammal assemblages in high-elevation drainages.
AB  - Heavy herbivory by ungulates can substantially alter habitat, but the indirect
      consequences of habitat modification for animal assemblages that rely on that
      habitat are not well studied. This is a particularly important topic given that
      climate change can alter plant-herbivore interactions. We explored short-term
      responses of small mammal communities to recent exclusion of Rocky Mountain elk
      (Cervus elaphus) in high-elevation riparian drainages in northern Arizona, where
      elk impacts on vegetation have increased over the past quarter century associated
      with climate change. We used 10-ha elk exclosures paired with unfenced control
      drainages to examine how browsing influenced the habitat use, relative abundance,
      richness and diversity of a small mammal assemblage. We found that the small
      mammal assemblage changed significantly after 5 years of elk exclusion. Relative
      abundance of voles (Microtus mexicanus) increased in exclosure drainages, likely
      due to an increase in habitat quality. The relative abundances of woodrats
      (Neotoma neomexicana) and two species of mice (Peromyscus maniculatus and P.
      boylii) decreased in the controls, while remaining stable in exclosures. The
      decline of mice in control drainages was likely due to the decline in shrub cover
      that they use. Thus, elk exclusion may have maintained or improved habitat for
      mice inside the exclosures while habitat quality and mouse abundance both
      declined outside the fences. Finally, small mammal species richness increased in
      the exclosures relative to the controls while species diversity showed no
      significant trends. Together, our results show that relaxation of heavy herbivore
      pressure by a widespread native ungulate can lead to rapid changes in small
      mammal assemblages. Moreover, exclusion of large herbivores can yield rapid
      responses by vegetation that may enhance or maintain habitat quality for small
      mammal populations. 

PMID- 23163814
TI  - A role for a global body for paediatric neurodisability.

PMID- 23163815
TI  - Stability of the Gross Motor Function Classification System after single-event
      multilevel surgery in cerebral palsy.

PMID- 23163816
TI  - Bone mineral density in children with congenital spinal dysfunction: updated
      technology for an old issue.

PMID- 23163817
TI  - Lower extremity bone mineral density in children with congenital spinal
      dysfunction.
AB  - AIM: To assess lower extremity bone mineral density (BMD) of children with
      congenital spinal dysfunction and examine factors that may influence BMD in this
      population. METHOD: Forty-four children (25 females, 19 males) aged 6 to 18 years
      (mean 11 y 11 mo, SD 3 y 6 mo) with congenital spinal dysfunction (35 with
      myelomeningocele, seven with lipomas, one with sacral agenesis, one with caudal
      regression) were enrolled in the study. A health survey including ambulatory
      status, history of bladder augmentation, and history of fracture was
      administered. Each participant had a physical examination including Tanner stage
      and neurological level. Dual-energy X-ray absorptiometry scans of the lateral
      distal femur (LDF) and, when possible, lumbar spine were obtained. We reported
      LDF BMD results as z-scores for three regions of interest (metaphyseal,
      metadiaphyseal, and diaphyseal). Univariable and multivariable analyses examined
      relationships between LDF BMD and the other variables. RESULTS: BMD was
      significantly related to ambulatory status (14 non-ambulatory, 15 partly
      ambulatory, 15 fully ambulatory) and neurological level (13 with low-level
      lesions, 15 medium-level, 16 high-level) in the univariable analysis (p<0.01 for
      both in all three regions). Neither history of fracture, nor Tanner stage, nor
      history of bladder augmentation showed a significant relationship to BMD. The
      significance of ambulatory status and neurological level in the univariable
      analysis failed to persist in the multivariable analysis of this study with a
      small sample size. INTERPRETATION: The LDF measurement proved to be a viable
      technique for assessing BMD in children with congenital spinal dysfunction. LDF
      BMD was sensitive to differences in three categories of ambulation. The overall
      influence of neurological level was not deemed as important as ambulation.

PMID- 23163818
TI  - Cerebral vasculitis in severe Kawasaki disease: early detection by magnetic
      resonance imaging and good outcome after intensive treatment.
AB  - Kawasaki disease is an acute vasculitis, that has a classic complication of
      acquired coronary artery aneurysm. Severe forms with multi-organ involvement or
      neurological dysfunction are rare. Cerebral vascular involvement has been related
      to large-vessel injury or cardioembolism, leading to focal brain infarction. A 4
      year-old female presented with unusual, rapidly catastrophic Kawasaki disease
      with refractory shock, acute renal failure, and coma, requiring intensive
      haemodynamic management. The observation of diffuse micro-haemorrhages (T2*
      weighted sequence) associated with white matter injury on brain magnetic
      resonance imaging (MRI) pointed towards lesions of the medium/small blood
      vessels. Cerebral vasculitis was suspected and the immunosuppressive treatment
      was increased Subsequently, the patient's recovery was rapid. On follow-up
      severe, bilateral vitritis was evident and surgery improved visual outcome. Early
      recognition of severe or unusual forms of Kawasaki disease could lead to more
      favourable outcome using appropriate treatment strategies. Diffuse cerebral micro
      haemorrhages on T2* brain MRI sequences might be a key sign for the diagnosis of
      medium or small cerebral vessel involvement.

PMID- 23163819
TI  - Ovotesticular disorder of sexual development due to 47,XYY/46,XY/45,X mixed
      gonadal dysgenesis in a phenotypic male presenting as cyclical haematuria:
      clinical presentation and assessment of long-term outcomes.
AB  - Ovotesticular disorder of sexual differentiation (OTDSD) is a rare cause of
      disorder of sexual differentiation predominantly having 46,XX karyotype, female
      phenotype and ambiguous genitalia. We report a 15-year-old having male body
      habitus, axillary and pubic hair, well-developed penis and right-descended testis
      with history of penoscrotal hypospadias correction, presenting with three
      episodes of cyclical haematuria, who biochemically had normal serum testosterone
      (338 ng dl(-1) ) which increased following hCG stimulation (614 ng dl(-1) ),
      elevated estradiol (17.35 pg ml(-1) ) along with elevated luteinising hormone
      (11.3 mIU l(-1) ) and follicle-stimulating hormone (31 mIU l(-1) ).
      Ultrasonography followed by micturating cystourethrogram and cystoscopy confirmed
      the presence of prostate, uterus, cervix and vagina draining into the urogenital
      sinus continuing till the penile urethra and left intra-abdominal gonad. Patient
      underwent hysterectomy and left gonadectomy. Histopathologic study of resected
      gonad confirmed presence of ovotestis. Low estradiol (1.2 pg ml(-1) ) following
      gonadectomy confirmed the ovotestis origin of estradiol. Chromosomal analysis
      revealed complex karyotype predominant being 47,XYY (50%) followed by 46,XY (26%)
      and 45,X (24%). This is perhaps the first report of 47,XYY/46,XY/45,X causing
      OTDSD in a phenotypic male.

PMID- 23163820
TI  - Editorial comment to nodal involvement at nephrectomy is associated with worse
      survival: a stage-for-stage and grade-for-grade analysis.

PMID- 23163822
TI  - Ultrasensitive immunoassay based on anodic near-infrared electrochemiluminescence
      from dual-stabilizer-capped CdTe nanocrystals.
AB  - A sandwich-typed near-infrared (NIR) electrochemiluminescence (ECL) immunoassay
      was developed with dual-stabilizer-capped CdTe nanocrystals (NCs) as ECL labels
      and alpha fetoprotein antigen (AFP) as model protein. The dual-stabilizer-capped
      NIR CdTe NCs were promising ECL labels because of their NIR ECL emission of 800
      nm, low anodic ECL potential of +0.85 V, and high biocompatibity, which can
      facilitate interference-free and highly sensitive ECL bioassays. Upon the
      immunorecognition of the immobilized AFP to its antibody labeled with dual
      stabilizer-capped CdTe NCs, the proposed immunoassay displayed increasing ECL
      intensity, leading to a wide calibration range of 10.0 pg/mL to 80.0 ng/mL with a
      detection limit of 5.0 pg/mL [signal-to-noise ratio (S/N) = 3] without coupling
      any signal amplification procedures. The NIR ECL immunoassay for real samples
      displayed very similar results with those of Ru(bpy)(3)(2+) reagent kit based
      commercial ECL immunoassay, which not only proved for the efficiency of NIR ECL
      from dual-stabilizer-capped CdTe NCs but also paved the road for development of
      novel ECL emitters and corresponding reagent kits.

PMID- 23163821
TI  - Transcription factor complex AP-1 mediates inflammation initiated by Chlamydia
      pneumoniae infection.
AB  - Chlamydia pneumoniae is responsible for a high prevalence of respiratory
      infections worldwide and has been implicated in atherosclerosis. Inflammation is
      regulated by transcription factor (TF) networks. Yet, the core TF network
      triggered by chlamydiae remains largely unknown. Primary human coronary artery
      endothelial cells were mock-infected or infected with C. pneumoniae to generate
      human transcriptome data throughout the chlamydial developmental cycle. Using
      systems network analysis, the predominant TF network involved receptor, binding
      and adhesion and immune response complexes. Cells transfected with interfering
      RNA against activator protein-1 (AP-1) members FOS, FOSB, JUN and JUNB had
      significantly decreased expression and protein levels of inflammatory mediators
      interleukin (IL)6, IL8, CD38 and tumour necrosis factor compared with controls.
      These mediators have been shown to be associated with C. pneumoniae disease.
      Expression of AP-1 components was regulated by MAPK3K8, a MAPK pathway component.
      Additionally, knock-down of JUN and FOS showed significantly decreased expression
      of Toll-like receptor (TLR)3 during infection, implicating JUN and FOS in TLR3
      regulation. TLR3 stimulation led to elevated IL8. These findings suggest that C.
      pneumoniae initiates signalling via TLR3 and MAPK that activate AP-1, a known
      immune activator in other bacteria not previously shown for chlamydiae,
      triggering inflammation linked to C. pneumoniae disease.

PMID- 23163823
TI  - Regioselective formation of tetrahydroselenophenes via 5-exo-dig-cyclization of 1
      butylseleno-4-alkynes.
AB  - Results on the synthesis of tetrahydroselenophene derivatives from 1-butylseleno
      4-alkynes by electrophilic cyclization using iodine as the electrophilic source
      are presented. This methodology was carried out via a simple process under mild
      reaction conditions providing the cyclized products in high yields. Electrophilic
      sources, such as PhSeBr, CuCl(2), and CuBr(2), were also used in this study. The
      tetrahydroselenophenes obtained by this protocol were submitted to cyanation,
      Suzuki, and Ullmann cross-coupling reactions to afford good yields of a cross
      coupled product.

PMID- 23163824
TI  - Structural and spectroscopic trends in a series of half-sandwich scorpionate
      complexes.
AB  - Fifteen half-sandwich scorpionate complexes [(L)M(NCMe)(3)](BF(4))(n) (L =
      tris(3,5-dimethylpyrazol-1-yl)methane, Tpm(Me,Me), n = 2, 1(M), M = Mn, Fe, Co,
      Ni; L = tris(3-phenylpyrazol-1-yl)methane, Tpm(Ph), n = 2, 2(M), M = Mn, Fe, Co,
      Ni; L = hydrotris(3,5-dimethylpyrazol-1-yl)borate, [Tp(Me,Me)](-), n = 1, 3(M), M
      = Fe, Co, Ni; L = hydrotris(3-phenyl-5-methylpyrazol-1-yl)borate, [Tp(Ph,Me)](-),
      n = 1, 4(M), M = Mn, Fe, Co, Ni) were prepared by addition of the tripodal
      ligands to solvated [M(NCMe)(x)](2+) (M = Mn, x = 4; M = Fe, Co, Ni, x = 6)
      precursor complexes. The product complexes were characterized by (1)H NMR (except
      M = Mn), UV-vis-NIR, and FTIR spectroscopy. The structures of 2(Mn), 2(Ni),
      3(Fe), 3(Co), and 4(Fe) were determined by X-ray crystallography. The data were
      consistent with complexes of high-spin divalent metal ions in idealized piano
      stool geometries in all cases. Consequent lability of the acetonitrile ligands
      will enable use of these complexes as synthetic precursors and as catalysts.
      Comparison to previously reported structures of 1(Fe), 1(Co), 2(Fe), and 2(Co),
      the triflate salt analogues of 4(Co) and 4(Ni), as well as related sandwich
      complexes (e.g., [(Tp(Me,Me))(2)M]) and solvated metal dications [M(NCMe)(6)](2+)
      reveals numerous trends in M-N bond lengths. Primary among these are the Irving
      Williams series, with significant structural effects also arising from ligand
      charge and sterics. Systematic trends in spectroscopic data were also observed
      which further elucidate these issues.

PMID- 23163825
TI  - Do high doses of AT(1)-receptor blockers attenuate central sympathetic outflow in
      humans with chronic heart failure?
AB  - In patients with CHF (chronic heart failure) sympathetic activity increases as
      cardiac performance decreases and filling pressures increase. We hypothesized
      that in patients with mild-to-moderate CHF, higher than conventional doses of an
      AT1-receptor [AngII (angiotensin II) type 1 receptor] antagonist would achieve
      greater central AT1-receptor blockade, resulting in diminished MSNA (muscle
      sympathetic nerve activity) and augmented MSNA variability, two indices of
      central effects on sympathetic outflow. In total, 13 patients with ischaemic
      cardiomyopathy [NYHA (New York Heart Association) class II-III] were weaned off
      all pharmacological RAS (renin-angiotensin system) modifiers, and then randomized
      to receive a low (50 mg/day) or high (200 mg/day) dose of losartan. Central
      haemodynamics, MSNA and its variability, plasma catecholamines, AngI (angiotensin
      I) and AngII and aldosterone were assessed both before and 3 months after
      randomization. Neither dose altered BP (blood pressure), PCWP (pulmonary
      capillary wedge pressure) or CI (cardiac index) significantly. Compared with 50
      mg daily, losartan 200 mg/day decreased MSNA significantly (P<0.05), by
      approximately 15 bursts/min, and increased MSNA variability within the 0.27-0.33
      Hz high-frequency range by 0.11 units(2)/Hz (P=0.06). PNE [plasma noradrenaline
      (norepinephrine)] fell in parallel with changes in MSNA (r=0.62; P<0.05). These
      findings support the hypothesis that higher than conventional doses of lipophilic
      ARBs (AT1-receptor blockers) can modulate the intensity and variability of
      central sympathetic outflow in patients with CHF. The efficacy and safety of this
      conceptual change in the therapeutic approach to heart failure merits prospective
      testing in clinical trials.

PMID- 23163826
TI  - Full-Mouth Rehabilitation of a Patient with Ectodermal Dysplasia Patient with
      Dental Implants.
AB  - Abstract   Oral findings in patients with ectodermal dysplasia (ED) include
      complete or partial hypodontia, anodontia, loss of vertical dimension of
      occlusion, protuberant lips, malformed and widely spaced conical-shaped teeth and
      underdeveloped alveolar ridges. These patients present a substantial challenge in
      dental treatment. This case report presents oral rehabilitation of a 22-year-old
      male patient diagnosed with ED using an implant-tooth supported telescopic
      partial denture at mandible and a tooth supported telescopic partial denture at
      maxilla. Implants in the mandible were placed at the sites of the right and left
      lateral incisor teeth. Following implant placement, the remaining buccal bone
      dehiscence was filled with deproteinized bovine bone graft and covered with
      resorbable membrane. To manage the vestibular insufficiency and to increase the
      keratinized mucosa in maxilla, bilateral acellular dermal matrix allograft was
      used on the right and left buccal aspects. Treatment described here improved the
      patient's functional and esthetic status while significantly restoring his oral
      health and self-esteem.

PMID- 23163827
TI  - Safety considerations for graphene: lessons learnt from carbon nanotubes.
AB  - Many consider carbon nanomaterials the poster children of nanotechnology,
      attracting immense scientific interest from many disciplines and offering
      tremendous potential in a diverse range of applications due to their
      extraordinary properties. Graphene is the youngest in the family of carbon
      nanomaterials. Its isolation, description, and mass fabrication has followed that
      of fullerenes and carbon nanotubes. Graphene's development and its adoption by
      many industries will increase unintended or intentional human exposure, creating
      the need to determine its safety profile. In this Account, we compare the lessons
      learned from the development of carbon nanotubes with what is known about
      graphene, based on our own investigations and those of others. Despite both being
      carbon-based, nanotubes and graphene are two very distinct nanomaterials. We
      consider the key physicochemical characteristics (structure, surface, colloidal
      properties) for graphene and carbon nanotubes at three different physiological
      levels: cellular, tissue, and whole body. We summarize the evidence for health
      effects of both materials at all three levels. Overall, graphene and its
      derivatives are characterized by a lower aspect ratio, larger surface area, and
      better dispersibility in most solvents compared to carbon nanotubes. Dimensions,
      surface chemistry, and impurities are equally important for graphene and carbon
      nanotubes in determining both mechanistic (aggregation, cellular processes,
      biodistribution, and degradation kinetics) and toxicological outcomes. Colloidal
      dispersions of individual graphene sheets (or graphene oxide and other
      derivatives) can easily be engineered without metallic impurities, with high
      stability and less aggregation. Very importantly, graphene nanostructures are not
      fiber-shaped. These features theoretically offer significant advantages in terms
      of safety over inhomogeneous dispersions of fiber-shaped carbon nanotubes.
      However, studies that directly compare graphene with carbon nanotubes are rare,
      making comparative considerations of their overall safety and risk assessment
      challenging. In this Account, we attempt to offer a set of rules for the
      development of graphene and its derivatives to enhance their overall safety and
      minimize the risks for adverse reactions in humans from exposure. These rules
      are: (1) to use small, individual graphene sheets that macrophages in the body
      can efficiently internalize and remove from the site of deposition; (2) to use
      hydrophilic, stable, colloidal dispersions of graphene sheets to minimize
      aggregation in vivo; and (3) to use excretable graphene material or chemically
      modified graphene that can be degraded effectively. Such rules can only act as
      guidelines at this early stage in the development of graphene-based technologies,
      yet they offer a set of design principles for the fabrication and safe use of
      graphene material that will come in contact with the human body. In a broader
      context, the safety risks associated with graphene materials will be entirely
      dependent on the specific types of graphene materials and how they are
      investigated or applied. Therefore, generalizations about the toxicity of
      "graphene" as a whole will be inaccurate, possibly misleading, and should be
      avoided.

PMID- 23163828
TI  - Three new amides from Microlepia pilosissima.
AB  - Phytochemical investigation of 70% EtOH extract of the dry fronds of Microlepia
      pilosissima has resulted in isolation of three new amides, (7E)-N-(3'-hydroxyl-4'
      methoxy)-phenylethyl-4-hydroxyl-cinnamamide (1), (7E)-N-(3',4',5'-trihydroxyl)
      phenylethyl-4-hydroxyl-cinnamamide (2), and (7E)-N-(3',4',5'-trihydroxyl)
      phenylethyl-4-methoxy-cinnamamide (3). Their structures were characterized by
      spectroscopic analysis and chemical method, including 1D NMR, 2D NMR, and HR-ESI
      MS.

PMID- 23163829
TI  - Vascularization of carotid plaque in recently symptomatic patients is associated
      with the occurrence of transcranial microembolic signals.
AB  - BACKGROUND AND PURPOSE: Microembolic signals (MES) are detectable in the middle
      cerebral artery by transcranial ultrasound downstream to atherosclerotic lesions
      of the internal carotid artery (ICA) in patients with stroke or transient
      ischaemic attack. The occurrence of MES predicts future risk of stroke in
      patients with symptomatic and asymptomatic carotid stenosis. The detection of
      intra-plaque neo-vascularization by contrast-enhanced ultrasound (CEUS) in
      atherosclerotic plaques of the ICA is associated with future
      cardiovascular/cerebrovascular events. We investigated whether there is an
      association between both surrogate markers of future vascular events. METHODS:
      Forty-one patients with symptomatic atherosclerotic plaques underwent ipsilateral
      transcranial ultrasound MES detection for 30 min followed by a CEUS investigation
      of the plaque. The occurrence and number of MES was documented, and the degree of
      intra-plaque neo-vascularization was measured semi-quantitatively. RESULTS:
      During the 30 min investigation, 17 patients had MES and nine of them showed neo
      vascularization of the atherosclerotic plaque. The remaining 24 patients did not
      have MES, and only in four patients of this group could plaque neo
      vascularization be demonstrated (P = 0.020). CONCLUSIONS: We found an association
      between the occurrence of MES and the presence of neo-vascularization in patients
      with symptomatic atherosclerotic carotid plaque. Therefore, plaque neo
      vascularization might also be a surrogate marker of future stroke risk.

PMID- 23163830
TI  - Quality care assessment of Parkinson's disease at a tertiary medical center.
AB  - The purpose of this study was to determine the level of care of Parkinson's
      disease patients based on the 10 American Academy of Neurology quality measures.
      We reviewed 1,367 charts and final analysis was completed on 123 subjects. A
      total of 1,461 outpatient neurology visits from 33 neurologists were reviewed and
      544 were included in the final analysis. Out of all 10 quality measures (13
      individual questions addressed), "annual review of Parkinson's medications" was
      the most frequently documented (97.2%) and "annual review of safety issues
      appropriate to the patient's stage of disease" was the least frequently
      documented item (7.2%). Movement disorders specialists recorded significantly
      more items than other neurologists (4.7 +/- 2.86 vs 3.3 +/- 1.97, p = .0437); the
      provider with the highest number of items addressed was a movement disorders
      nurse practitioner (8.22 out of 13). None of the patient characteristics
      influenced the rates of documentation of the 10 quality measures. The wide
      variation of documentation rates could be addressed by comprehensive standardized
      templates to be reviewed and updated at each visit.

PMID- 23163831
TI  - Economical aspect of biological therapy in inflammatory conditions in Hungary.
AB  - INTRODUCTION: There has been a burst in the use of biological therapies in the
      past decade resulting in increasing costs. In 2006 - 2010 the following
      biological agents were available in Hungary: adalimumab, certolizumab,
      etanercept, golimumab, infliximab, rituximab, tocilizumab, and ustekinumab. All
      biological agents except rituximab were first line therapies; rituximab was a
      second line option in rheumatoid arthritis. AREAS COVERED: Data of the financing
      system related to health care services from the data warehouse of the Hungarian
      National Health Insurance Fund were in inflammatory conditions. Our analysis
      showed a constant increase in number of patients and overall cost of biological
      therapy as well as annual cost of biological agents. Distribution of first choice
      of biological therapy was compared in different diseases. Time from diagnosis to
      start of biological therapy showed relatively high deviations. EXPERT OPINION: In
      order to achieve both health benefit and cost-effectiveness it is crucial that
      biological therapy is initiated early enough in the course of the disease, after
      the failure of non-biological therapies. Health authorities in close
      collaboration with clinical decision-makers should ensure that early detection of
      the disease and early initiation of appropriate therapies-including non
      biological and biological therapies-are carried out in the health care systems.

PMID- 23163832
TI  - Effect of incisor position on the self-perceived psychosocial impacts of
      malocclusion among Chinese young adults.
AB  - OBJECTIVE: To evaluate the impact of the incisor position on the self-perceived
      psychosocial impacts of malocclusion among Chinese young adults. MATERIALS AND
      METHODS: This cross-sectional study included a convenience sample of 17.1- to
      22.3-year-old young adults (n = 1005). The five groups represented were normal
      occlusion as well as incisor Class I, Class II/1, Class II/2, and Class III
      malocclusion. For clinical assessment, the incisor relationship was evaluated
      according to the British Standards Institute Incisor Classification, and the self
      perception of dental esthetics was assessed using the Psychosocial Impact of
      Dental Aesthetics Questionnaire (PIDAQ). Statistical analysis involved the
      analysis of variance and Tukey multiple-comparison post hoc tests. RESULTS:
      Psychosocial impacts were different among the five groups for the four PIDAQ
      domains (P < .001 for all four domains). Statistically significant differences
      were found between the four malocclusion groups and the normal occlusion group in
      all four domains (P < .001 for all four domains). Furthermore, statistically
      significant differences were found between four malocclusion groups. CONCLUSIONS:
      All four malocclusion groups had more severe psychosocial impacts than the normal
      occlusion group in the four PIDAQ domains. Statistically significant differences
      were also found between the four malocclusion groups; these malocclusion groups
      ranked by score, highest to lowest, were Class III, Class II/1, Class II/2, and
      Class I.

PMID- 23163833
TI  - Differentiating two- from three-dimensional mental rotation training effects.
AB  - Block videogame training has consistently demonstrated transfer effects to mental
      rotation tasks, yet how variations in training influence performance with
      different stimuli remains unclear. In this study, participants took mental
      rotation assessments before and after a 3-week training programme based on 2D or
      3D block videogames. Assessments varied in terms of dimensionality (2D or 3D) and
      stimulus type (polygon or body). Increases in videogame scores throughout
      training were correlated with mental rotation improvements. In particular, 2D
      training led to improvements in 2D tasks, whereas 3D training led to improvements
      in both 2D and 3D tasks. This effect did not depend on stimulus type,
      demonstrating that training can transfer to different stimuli of identical
      dimensionality. Interestingly, traditional gender differences in 3D mental
      rotation tasks vanished after 3D videogame training, highlighting the
      malleability of mental rotation ability given adequate training. These findings
      emphasize the influence of dimensionality in transfer effects and offer promising
      perspectives to reduce differences in mental rotation via designed training
      programmes. 

PMID- 23163835
TI  - Development of a nomogram for predicting the stone-free rate after transurethral
      ureterolithotripsy using semi-rigid ureteroscope.
AB  - OBJECTIVES: To develop and to internally validate a novel nomogram for predicting
      the stone-free rate after transurethral ureterolithotripsy. METHODS: A total of
      412 patients with 534 ureteral stones were treated with transurethral
      ureterolithotripsy using semi-rigid ureteroscopes. Treatment efficacy was
      evaluated 3 months after the procedure. Multivariate stepwise logistic regression
      analysis was used to identify independent predictors of being stone-free in the
      model-building set. A total of 427 stones (80% of 534) were randomly allocated
      for identification and statistical analysis to build the model, and the remaining
      107 (20%) were used for cross-validation. A nomogram for the stone-free rate was
      developed based on the final logistic regression model. RESULTS: Stone length,
      number of stones, stone location and the presence of pyuria were independent
      factors related to the stone-free rate after transurethral ureterolithotripsy
      treatment, and these were used to develop a nomogram. In this nomogram, the area
      under the receiver operating characteristic curve was 0.7432 for the nomogram,
      0.5641 for stone size, 0.5908 for the number of stones, 0.6594 for stone location
      and 0.6076 for pyuria. Validation using 20% of the data also achieved a
      reasonable predictive accuracy (area under the receiver operating characteristic
      curve = 0.682). CONCLUSIONS: The first nomogram for predicting the stone-free
      rate after transurethral ureterolithotripsy was developed. It has a reasonable
      predictive accuracy, and in combination with extracorporeal shock wave
      lithotripsy nomograms, it might be useful for deciding treatment methods.

PMID- 23163834
TI  - Metabolomics of cerebrospinal fluid from humans treated for rabies.
AB  - Rabies is a rapidly progressive lyssavirus encephalitis that is statistically
      100% fatal. There are no clinically effective antiviral drugs for rabies. An
      immunologically naive teenager survived rabies in 2004 through improvised
      supportive care; since then, 5 additional survivors have been associated with use
      of the so-called Milwaukee Protocol (MP). The MP applies critical care focused on
      the altered metabolic and physiologic states associated with rabies. The aim of
      this study was to examine the metabolic profile of cerebrospinal fluid (CSF) from
      rabies patients during clinical progression of rabies encephalitis in survivors
      and nonsurvivors and to compare these samples with control CSF samples.
      Unsupervised clustering algorithms distinguished three stages of rabies disease
      and identified several metabolites that differentiated rabies survivors from
      those who subsequently died, in particular, metabolites related to energy
      metabolism and cell volume control. Moreover, for those patients who survived,
      the trajectory of their metabolic profile tracked toward the control profile and
      away from the rabies profile. NMR metabolomics of human rabies CSF provide new
      insights into the mechanisms of rabies pathogenesis, which may guide future
      therapy of this disease.

PMID- 23163836
TI  - Peptidoglycan-induced T helper 2 immune response in mice involves interleukin-10
      secretion from Langerhans cells.
AB  - Patients with atopic dermatitis (AD) have superficial skin colonization with
      Staphylococcus aureus and an increased number of T helper (Th)2 cells in their
      peripheral blood. The purpose of this study was to clarify the involvement of
      interleukin (IL)-10 secretion from Langerhans cells (LCs) in staphylococcal
      peptidoglycan (PEG)-induced Th2 immune responses in mice. Mice were primed with
      LCs pulsed with PEG (or LPS) and ovalbumin (OVA) and then given a booster OVA
      injection 2 days later in the hind footpad. Five days after the OVA injection,
      cytokine responses in the draining popliteal lymph nodes were investigated by RT
      PCR and ELISA. Production of both IL-10 and IL-12 by cultured LCs was detected by
      ELISA. Administration of PEG- or LPS-stimulated LCs into the hind footpads of the
      mice induced Th2-prone and Th1-prone immune responses, respectively, as
      represented by expression of IL-4 and interferon-gamma. In vitro experiments
      showed that PEG induced greater production of IL-12 p40 from LCs than did LPS,
      whereas LPS induced greater production of IL-12 p70 from LCs than did PEG.
      Furthermore, it was found that PEG-stimulated LCs induced greater production of
      IL-10 than did LPS-stimulated LCs, and that neutralization of IL-10 augmented IL
      12 p70 production and inhibited Th2 development by PEG-stimulated LCs. These
      results suggest that PEG can induce Th2 development through down-regulation of IL
      12 p70 production by LCs in an IL-10 production-dependent manner and would
      explain the role of S. aureus colonization in patients with AD.

PMID- 23163837
TI  - MRI of pallidal involvement in Beta-ketothiolase deficiency.
AB  - Beta-ketothiolase (BKT) deficiency is a rare autosomal recessive metabolic
      disorder, which causes episodic severe metabolic acidosis. Average onset of
      disease is from 6 to 24 months. Imaging findings relating to this entity have
      rarely been reported. We report a case of a 5-year-old girl with BKT deficiency
      with isolated focal T2 hyperintensities involving the globi pallidi, which
      demonstrated restricted diffusion. To our knowledge, these imaging findings have
      not been previously reported in the setting of BKT deficiency. 

PMID- 23163838
TI  - Basilar artery stroke in childhood.
AB  - AIM: Little is known about basilar artery stroke (BAS) in children. The objective
      of this study was to calculate the incidence of BAS in children and to analyse
      the clinical presentation, risk factors, radiological findings, therapeutic
      approaches, and outcome of BAS in childhood. METHOD: A prospective, population
      based study including children with arterial ischaemic stroke and a systematic
      review of the literature was undertaken. RESULTS: Seven children with BAS were
      registered at the Swiss Neuropaediatric Stroke Registry between January 2000 and
      June 2011 (incidence 0.037 per 100,000 children per year, 95% confidence interval
      [CI] 0.013-0.080). A further 90 cases were identified through the literature
      search. The majority of patients were male (73 males, 24 females) and the median
      age was 9 years (interquartile range [IQR]=6-13y). The median Pediatric National
      Institutes of Health Stroke Scale (PedNIHSS) score was 15 (IQR=4-27). Presenting
      signs and symptoms comprised impaired consciousness (n=64), quadri- or
      hemiparesis (n=58), bulbar dysfunction (n=46), vomiting, nausea (n=43), and
      headache (n=41). Prodromes occurred in 43% of cases. Aetiology was largely
      vasculopathic (n=38), but often unknown (n=40). Time to diagnosis varied from
      hours days; six patients received antithrombotic, thrombolytic, or mechanical
      endovascular treatment 12 hours or less after symptom onset. Outcome was good
      (modified Rankin Scale 0-2) in 45 patients; eight died. PedNIHSS score of up to
      17 was a prognostic factor for good outcome. INTERPRETATION: BAS is rare in
      children. Compared with adults, outcome is more favourable despite a considerable
      delay in diagnosis and treatment. Outcome was better in children with a PedNIHSS
      score of 17 or less.

PMID- 23163839
TI  - Stereoselective synthesis of deuterium-labeled (2S)-cyclohexenyl alanines,
      biosynthetic intermediates of cinnabaramide.
AB  - Dideuterated beta-cyclohexenylalanines, proposed biosynthetic intermediates of
      the cinnabaramides, can be obtained from chiral alkynols via a sequence of Irland
      Claisen rearrangement, ring closing metathesis, and radical decarboxylation.
      Feeding experiments indicate that both (2S)-beta-cyclohexenylalanines can be
      incorporated into cinnabaramide, while the configuration at the cyclohexenyl ring
      does not restrict biosynthetic processing.

PMID- 23163840
TI  - Trace-level potentiometric detection in the presence of a high electrolyte
      background.
AB  - Polymeric membrane ion-selective electrodes (ISEs) have become attractive tools
      for trace-level environmental and biological measurements. However, applications
      of such ISEs are often limited to measurements with low levels of electrolyte
      background. This paper describes an asymmetric membrane rotating ISE
      configuration for trace-level potentiometric detection with a high-interfering
      background. The membrane electrode is conditioned in a solution of interfering
      ions (e.g., Na(+)) so that no primary ions exist in the ISE membrane, thus
      avoiding the ion-exchange effect induced by high levels of interfering ones in
      the sample. When the electrode is in contact with the primary ions, the
      interfering ions in the membrane surface can be partially displaced by the
      primary ions due to the favorable ion-ligand interaction with the ionophore in
      the membrane, thus causing a steady-state potential response. By using the
      asymmetric membrane with an ion exchanger loaded on the membrane surface, the
      diffusion of the primary ions from the organic boundary layer into the bulk of
      the membrane can be effectively blocked; on the other hand, rotation of the
      membrane electrode dramatically reduces the diffusion layer thickness of the
      aqueous phase and significantly promotes the mass transfer of the primary ions to
      the sample-membrane interface. The induced accumulation of the primary ions in
      the membrane boundary layer largely enhances the nonequilibrium potential
      response. By using copper as a model, the new concept offers a subnanomolar
      detection limit for potentiometric measurements of heavy metals with a high
      electrolyte background of 0.5 M NaCl.

PMID- 23163841
TI  - Photodynamic efficiency of cationic meso-porphyrins at lipid bilayers: insights
      from molecular dynamics simulations.
AB  - Porphyrin derivatives have applications as photoactive drugs in photodynamic
      therapy. However, little is known about their interactions with phospholipid
      membranes at the molecular level. We employed molecular dynamics simulations to
      model the binding between a series of cationic meso-(N-methyl-4
      pyridinium)phenylporphyrins and anionic phosphatidylglycerol lipid bilayers. This
      was done in the presence of molecular oxygen within the membrane. The ability of
      various porphyrins to cause photodamage was quantified in terms of their
      immersion depth and degree of exposition to a higher oxygen concentration inside
      the membrane. Simulations showed that the photodynamic efficiency could be
      improved as the number of hydrophobic phenyl substituents attached to the
      porphyrinic ring increased. In the specific case of porphyrins containing two
      hydrophobic and two charged substituents, the cis isomer was significantly more
      efficient than the trans. These results correlate well with previous experimental
      observations. They highlight the importance of both the total charge and
      amphiphilicity of the photosensitizer for its performance in photodynamic
      therapy.

PMID- 23163842
TI  - Green tea and incidence of colorectal cancer: evidence from prospective cohort
      studies.
AB  - A systematic meta-analysis of prospective cohort studies on green tea consumption
      and colorectal cancer was performed to determine whether green tea has a
      chemopreventive effect against colorectal cancer. Six eligible cohort studies
      involving 352,275 participants and 1675 cases of colorectal cancer were
      identified. Combined relative risk (RR) ratios for the highest vs. lowest and
      increment of 1 cup/day green tea consumption levels were calculated. The combined
      RR of 0.90 (95% CI: 0.72-1.08) was found comparing highest vs. lowest green tea
      consumption levels for colorectal cancer. No significant differences by cancer
      site were found, but an inverse association between green tea and incidence of
      colorectal cancer (RR: 0.70; 95% CI: 0.55-0.85) and colon cancer (RR: 0.69; 95%
      CI: 0.48-0.98) was demonstrated in Shanghai population. Singapore men had a
      higher risk of colorectal cancer (RR: 1.36; 95% CI: 1.06-1.74). Furthermore, an
      increase in green tea consumption of 1 cup/day was not associated with incidence
      of colorectal cancer (RR: 0.97; 95% CI: 0.91-1.03). Despite the limited evidence
      from Shanghai studies in support of green tea as potential chemopreventive agents
      against colorectal cancer, available data from prospective cohort studies are
      insufficient to conclude that green tea may protect against colorectal cancer.

PMID- 23163843
TI  - Selenium and colorectal adenomas risk: a meta-analysis.
AB  - Selenium, as an important component of some antioxidants, has been suggested to
      have protective effects against colorectal adenomas. This meta-analysis examined
      the association between selenium level in blood and risk of colorectal adenomas.
      Data from 7 studies (3 cross-sectional studies, 3 case-control studies, 1 nested
      case-control study) published before December 2011 was included in this meta
      analysis. Fixed and random-effects model was explored to calculate odds ratio
      (OR) and 95% confidence intervals (CI). Heterogeneity among studies was measured
      using Cochrane Q-test together with the I (2) statistic. There was a significant
      inverse correlation between selenium level and colorectal adenomas risk according
      to fixed-effects model. The overall OR of highest selenium level to lowest for
      colorectal adenomas is 0.67 (95% CI: 0.55-0.81). Heterogeneity was moderate among
      the pooled studies (P = 0.05 for the Q test, I (2) = 48%). These results
      suggested a protective effect of selenium for colorectal adenomas. Some factors,
      such as age, gender, smoking, and characteristics of the adenomas need to be
      further considered within the association between selenium levels and risk of
      colorectal adenomas.

PMID- 23163844
TI  - Whole grain, dietary fiber, and incidence of endometrial cancer in a Danish
      cohort study.
AB  - Whole grains and dietary fiber might be inversely associated with endometrial
      cancer risk through their effects on sex hormone metabolism and body fat. We
      investigated whether a higher intake of whole grains and dietary fiber was
      associated with a lower incidence of endometrial cancer in the Diet, Cancer and
      Health cohort of 29,875 women aged 50-64 years at enrollment in 1993-1997.
      Information on diet and lifestyle was derived from self-administered
      questionnaires. The incidence rate ratios and 95% confidence intervals were
      estimated based on a Cox proportional hazards model. Of the 24,418 women included
      as cohort members, 217 had a diagnosis of endometrial cancer. No clear
      associations were found between intake of whole grains or dietary fiber and the
      incidence of endometrial cancer.

PMID- 23163845
TI  - Serum albumin is superior to prealbumin for predicting short-term recurrence in
      patients with operable colorectal cancer.
AB  - The relationship between preoperative prealbumin and cancer survival has not been
      fully elucidated. The purpose of this study was to examine the relationship
      between preoperative nutritional conditions, including prealbumin and albumin
      concentrations, and the risk of recurrence in cases with operable colorectal
      carcinoma. One hundred fifty-eight patients who underwent elective colorectal
      resection were analyzed in this study. Of the eligible cases, 56 (35.4%) had
      decreased serum prealbumin and 15 (9.5%) had decreased serum albumin
      preoperatively. Among 158 cases in this study, 18 (11.4%) had disease recurrence.
      In the univariate analysis, the depth of tumor invasion, lymph node metastasis,
      lymphovascular invasion, serum albumin, prealbumin, and carcinoembryonic antigen
      were the factors significantly associated with disease recurrence. Multivariate
      analysis demonstrated that only serum albumin was a predictor of the recurrence;
      however, serum prealbumin lost its significance on multivariate analysis. Time to
      tumor recurrence by Kaplan-Meier curves significantly differed among patients
      with low serum albumin and prealbumin level. Our results suggest that prealbumin
      and albumin may be sensitive indicators of the risk of recurrent disease;
      however, low serum albumin levels are more useful than prealbumin in predicting
      short-term disease recurrence in operable colorectal cancer.

PMID- 23163846
TI  - Preoperative nutritional assessment and prognosis in patients with foregut
      tumors.
AB  - Malnourished patients with gastrointestinal tumours are at risk for postoperative
      complications and death. The aim of this study was to determine which nutritional
      assessment method better predicts outcome. Seventy-four patients, 45 men and 29
      women; mean (SD) age of 63 (102) yr (range = 34 to 83), undergoing surgical
      resections for esophageal (n = 19) gastric (n = 43) and pancreatic (n = 12)
      tumors were preoperatively assessed by Patient Generated Subjective Global
      Assessment, anthropometry, and by laboratory sampling. Forty-three (58%) of them
      were unnourished; 25 Subjective Global Assessment (SGA)-A, 34 SGA-B, and 15 SGA-C
      cases. Mean (SD) of dominant hand adductor pollicis muscle thickness (DAPM) was
      13 (3.5) mm and mean (SD) serum albumin was 3.8 (0.5) g/dL. Mean (SD) hospital
      staying for patients who complicated and died was 34 (29) days and 23 (13) days
      for survivors (not significant); SGA-B cases were significantly associated with
      higher mortality (n = 12, P<0.001). Patients with a mean (SD) DAPM below 10.8
      (3.7) mm died more frequently than those with a mean (SD) greater than 14 (3) mm
      (P < 0.001). None of the methods was significantly related to hospital stay, but
      receiver operating characteristic curves (95% confidence interval) for PG-SGA and
      DAPM thickness (0.75 and 0.74) reliably predicted mortality (P<0.001) and these
      methods may be used as preoperative parameter.

PMID- 23163847
TI  - Do tobacco and alcohol modify protective effects of diet on oral carcinogenesis?
AB  - Recent systematic reviews concluded that the frequent consumption of fruits and
      vegetables is inversely associated with the risk of oral cancer. We assessed this
      association, specifically comparing results obtained to nonsmokers and smokers,
      as well to nondrinkers and drinkers. We conducted a case-control study involving
      296 patients with oral squamous cell carcinoma (cases) attended in 3 major
      hospitals of Sao Paulo, Brazil, paired with 296 controls, recruited from
      outpatient units of the same hospitals. Multivariate models assessed the effect
      of fruits and salads according to smoking and drinking. The intake of fruit was
      associated with the prevention of the disease in the specific assessment among
      light [odds ratio (OR) = 0.46; 95% confidence interval (CI) = 0.27-0.78) and
      heavy (OR = 0.30; 95% CI = 0.14-0.65) smokers. The same was observed for
      vegetables consumption. For nonsmokers, no fruit (OR = 50; 95% CI = 0.22-1.12) or
      vegetable (for tomato, OR = 0.53; 95% CI = 0.31-0.93) was associated with reduced
      risk of oral and oropharyngeal cancer. Similar results were found in the
      stratified analysis according to drinking status with OR = 0.51 (95% CI = 0.30
      0.87) and 0.18 for fruits (95% CI = 0.07-0.45), respectively, for light and heavy
      drinkers. This observation suggests that the protective effect of fruit and salad
      intake may modulate the deleterious effects from tobacco and alcohol.

PMID- 23163848
TI  - Obesity and excess protein and carbohydrate consumption are risk factors for
      thyroid cancer.
AB  - Conflicting data concerning the association between obesity and differentiated
      thyroid cancer (DTC) may be attributed to the lack of records showing dietary
      intake and inadequate evaluation of nutrient composition. We evaluated 115 DTC
      patients carefully paired with 103 healthy control individuals by using a
      structured questionnaire, including a 24-h recordatory during 3 days, to
      investigate calorie intake and macronutrient (proteins, carbohydrates, and
      lipids) composition of the diet. We observed that excess weight (body mass index
      > 25 kg/m(2)) increased individual susceptibility to DTC [odds ratio (OR) =
      3.787; 95% confidence interval (CI) = 1.115-6.814; P < 0.0001). This augmented
      risk was evident in women (OR = 1.925; 95% CI = 1.110-3.338; P = 0.0259) but not
      in men (P = 0.3498). Excess calorie intake was more frequent in patients with DTC
      than in controls (OR = 5.890; 95% CI = 3.124-11.103; P < 0.0001), and both excess
      protein (OR = 4.601; 95% CI = 1.634-12.954; P = 0.0039) and carbohydrate (OR =
      4.905; 95% CI = 2.593-9.278; P < 0.0001) consumption were associated with an
      increased risk of DTC, contrarily to lipid/fiber intake and physical activity (P
      = 0.894 and 0.5932, respectively). In conclusion, our data indicate that
      overweight and risk of DTC are associated with higher protein and carbohydrate
      consumption than the rates recommended by the World Health Organization. The
      nutritional orientation should be part of preventive strategy targets designed to
      combat the increasing incidence of both obesity and DTC.

PMID- 23163849
TI  - Effects of dietary genistein on hormone-dependent rat mammary carcinogenesis
      induced by ethyl methanesulphonate.
AB  - Genistein, a major soy isoflavone having weak estrogenic activities, has been
      suggested to reduce the risk of breast cancer incidence. However, many studies
      have yielded inconsistent results. We investigated the effects of dietary
      genistein on the development of breast cancer using ethyl methanesulphonate (EMS)
      chemically induced rat model of hormone-dependent mammary carcinoma. Female
      Wistar King A rats were orally given EMS for 12 wk and fed isoflavone-free NIH
      07PLD diets with or without genistein, beginning immediately after weaning
      period. All EMS-treated rats fed either diet developed estrogen and/or
      progesterone receptor-positive mammary carcinoma by 24 wk. The addition of either
      low or high genistein, which produced the plasma concentrations comparable with
      those observed in humans consuming high soy diets, did not show any preventive
      activity. Soy-containing pellet food, exhibiting substantial plasma
      concentrations of isoflavones such as genistein, daidzein, equol, and glycitein,
      significantly increased the latency periods, compared to either NIH-07PLD diet
      with low (P = 0.027) or high (P = 0.034) genistein. Body weights, total EMS
      uptakes, and urinary estradiol concentrations were not significantly different
      among groups. These data indicate that genistein does not exert clear preventive
      effects and that isoflavone components other than genistein might be preventive
      against hormone-dependent mammary carcinogenesis.

PMID- 23163850
TI  - All-trans-retinoic acid and the glycolipid alpha-galactosylceramide combined
      reduce breast tumor growth and lung metastasis in a 4T1 murine breast tumor
      model.
AB  - Vitamin A compounds are promising for cancer prevention and reducing risk of
      recurrence. Herein we have evaluated the combination of all-trans-retinoic acid
      (RA), a vitamin A metabolite, and alpha-galactosylceramide (alphaGalCer), a lipid
      immune activator, in Balb/C mice inoculated with syngeneic 4T1 breast tumor cells
      on reduction in breast tumor growth and lung metastasis. In Balb/c inoculated
      with the syngenic 4T1 primary tumor, and administered dendritic cells treated
      with RA + alphaGalCer, the size of the primary tumor and the number of lung
      metastatic foci were reduced. When 4T1 cells were introduced into the circulation
      as a model of hematogenous spread of tumor cells and RA and alphaCalCer were
      administered directly to mice without dendritic cells, lung metastatic foci were
      reduced 70% (P < 0.05), whereas each agent alone resulted in an intermediate
      decrease. Concomitantly, the expression of matrix metalloproteinases (MMP),
      membrane type-1 (MT1)-MMP and MMP3, were reduced by RA + alphaGalCer in lung.
      MMP3 protein was also reduced in plasma and culture supernatants from RA +
      alphaGalCer-treated 4T1 cells. Together, our results provide new evidence that a
      nutritional-immunological combination of RA + alphaGalCer may be promising for
      preventing or slowing the growth of metastatic foci, and suggest reduced MMP
      production as a possible mechanism.

PMID- 23163851
TI  - 2,4-bis (p-hydroxyphenyl)-2-butenal (HPB242) induces apoptosis via modulating E7
      expression and inhibition of PI3K/Akt pathway in SiHa human cervical cancer
      cells.
AB  - The Maillard reaction is a chemical reaction occurring between an amino acid and
      a reducing sugar, usually requiring thermal processing. Maillard reaction
      products (MRPs) have antioxidant, antimutagenic, and antibacterial effects, and
      although 2,4-bis (p-hydroxyphenyl)-2-butenal (HPB242), a fructose-tyrosine MRP,
      appears to inhibit proliferation of cancer cells, its mechanism of action has not
      been studied in detail. We found that HPB242 treatment modulated expression of
      cyclins and tumor suppressor genes in SiHa human cervical cancer cell lines:
      cyclins and phospho-pRB were downregulated, whereas the expression of CDK
      inhibitors and p53 was enhanced. HPB242 induced apoptosis dose-dependently by
      suppressing E7 expression and leading to sub-G1 cell-cycle arrest in SiHa cell
      lines; treatment also led to the proteolytic cleavage of caspase-3, -9, and poly
      (ADP-ribose) polymerase. Moreover, HPB242 upregulated Fas expression, altered
      expressions of pro- and antiapoptotic factors, and also inhibited nuclear
      translocation of nuclear factor kappaB and phosphorylation of IkappaB. HPB242
      treatment decreased phosphatidyl inositol-3 kinase and p-Akt expression levels,
      demonstrating that this survival pathway may also be inhibited by HPB242.
      Cumulatively, HPB242 promotes apoptosis by influencing E7 expression, inducing
      cell-cycle arrest at sub-G1 phase, and promoting both intrinsic (mitochondrial)
      and extrinsic (Fas-dependent) apoptosis in SiHa human cervical cancer cells.

PMID- 23163852
TI  - Effects of Thymus serpyllum extract on cell proliferation, apoptosis and
      epigenetic events in human breast cancer cells.
AB  - Thymus (T.) serpyllum (wild thyme) is an aromatic medicinal plant due to its
      several biological properties, including anticancer activity. Breast cancer is
      one of the most common malignancies and increasing evidence supports that it is
      not only a genetic but also an epigenetic disease. Epigenetics investigates
      changes in gene expression caused by mechanisms that do not involve alterations
      in DNA sequence. DNA methylation and histone acetylation are the most widely
      studied epigenetic changes in cancer cells. This study evaluated the effects of
      T. serpyllum on apoptosis and epigenetic events in breast cancer cells. XTT cell
      viability assay was used to determine cytotoxicity. DNA fragmentation and caspase
      3/7 activity assays were used in the assesment of apoptosis. DNA
      methyltransferase (DNMT) and histone deacetylase (HDAC) activities were evaluated
      by ELISA and verified by qRT-PCR. T. serpyllum extract induced significant
      cytotoxicity in breast cancer cells (MCF-7 and MDA-MB-231) but not in normal
      cells. It also induced apoptosis and inhibited the DNMT and HDAC activities in
      MDA-MB-231 cells. In the present study, the first preliminary data on the effects
      of the methanolic extract of T. serpyllum in normal and breast cancer cells were
      obtained and suggest that T. serpyllum may be a promising candidate in the
      development of novel therapeutic drugs for breast cancer treatment.

PMID- 23163853
TI  - Diallyl disulfide-induced apoptosis in a breast-cancer cell line (MCF-7) may be
      caused by inhibition of histone deacetylation.
AB  - The health benefits of garlic have been proven by epidemiological and
      experimental studies. Diallyl disulphide (DADS), the major organosulfur compound
      found in garlic oil, is known to lower the incidence of breast cancer both in
      vitro and in vivo. The studies reported here demonstrate that DADS induces
      apoptosis in the MCF-7 breast-cancer cell line through interfering with cell
      cycle growth phases in a way that increases the sub-G(0) population and
      substantially halts DNA synthesis. DADS also induces phosphatidylserine
      translocation from the inner to the outer leaflet of the plasma membrane and
      activates caspase-3. Further studies revealed that DADS modulates the cellular
      levels of Bax, Bcl-2, Bcl-xL, and Bcl-w in a dose-dependent manner, suggesting
      the involvement of Bcl-2 family proteins in DADS induced apoptosis. Histone
      deacetylation inhibitors (HDACi) are known to suppress cancer growth and induce
      apoptosis in cancer cells. Here it is shown that DADS has HDACi properties in MCF
      7 cells as it lowers the removal of an acetyl group from an acetylated substrate
      and induces histone-4 (H4) hyper-acetylation. The data thus indicate that the
      HDACi properties of DADS may be responsible for the induction of apoptosis in
      breast cancer cells.

PMID- 23163854
TI  - Effect of germinated soy protein on the growth of HeLa cervical cancer cells in
      female athymic mice.
AB  - Previous studies showed that germination could improve the antiproliferative
      effect of soy protein on cervical cancer cells and that a peptide fraction (MAPF)
      from germinated soybeans decreases the expression of PTTG1 and TOP2A (2 genes
      considered as therapeutic targets) causing apoptosis of cancer cells. The aim of
      this work was to study the effect of feeding germinated soybean protein diets on
      the tumor growth in nude mice inoculated with cervical cancer cells and identify
      the bioactive component. Mice were randomly assigned to 1 of the 6 dietary groups
      based in AIN-93G formulation with 6 protein sources: casein, ungerminated soy
      protein (SP), and SP from 2 and 6 days of germination, with and without ethanol
      soluble phytochemicals (ESPC). Compared with casein-fed controls, the tumor
      volumes after 5 wk were reduced by 44.6% by ungerminated SP, 98.9% by 2-day
      germinated SP, 97.7% by 2-day-germinated SP without ESPC, 94.7% by 6-day
      germinated SP, and 92.7% by 6-day-germinated SP without ESPC (P < 0.05). Liquid
      chromatography coupled with tandem mass spectrometry analysis of MAPF showed that
      the bioactive peptide might be the leginsulin, a peptide involved in signal
      transduction of soybean cells. Germination is a simple procedure that could help
      to increase the anticancer activity of soy protein probably through generation of
      biologically active peptides.

PMID- 23163855
TI  - Effects of Tepary bean (Phaseolus acutifolius) protease inhibitor and semipure
      lectin fractions on cancer cells.
AB  - Some natural and synthetic protease inhibitors (PI), such as the Bowman-Birk PI
      from soybean, have anticancer effects. We previously purified and characterized a
      Bowman-Birk-type PI from Tepary bean (Phaseolus acutifolius) seeds (TBPI). A
      semipure protein fraction containing this inhibitor, when tested its in vitro
      effect on transformed cells, showed a differential cytotoxic effect, as well as
      an increase in cell attachment to culture dishes. In this article we report that
      lectins were responsible for the cytotoxic effect previously observed, exhibiting
      a differential, antiproliferative effect on nontransformed cells and on different
      lineages of cancer cells. Although the purified TBPI lacked cytotoxicity, it was
      found to be responsible for the increase in cell adhesion, decreasing culture
      dishes' extracellular matrix degradation, leading to a decrease of the in vitro
      cell invasion capacity. This effect coincided with the suppression of Matrix
      Metalloproteinase-9 activity. These results indicate that Tepary bean seeds
      contain at least 2 different groups of bioactive proteins with distinct effects
      on cancer cells.

PMID- 23163856
TI  - Studies on the chemopreventive effect of carnitine on tumorigenesis in vivo,
      using two experimental murine models of colon cancer.
AB  - Carnitine is known for its essential role in intermediary metabolism. In vitro
      studies suggest that its antioxidant and anti-inflammatory properties are
      potentially beneficial toward cancer prevention. This study tested effects of
      carnitine on the development of colon cancer in vivo using 2 murine models:
      azoxymethane (AOM) treatment as a model of carcinogen-induced colon cancer and a
      genetically induced model using Apc (Min/+) mice. AOM and Apc (Min/+) mice
      divided into dietary groups varying in lipid content, with or without carnitine
      supplementation (0.08%). AOM-exposed mice on a high butterfat diet had
      significantly increased aberrant crypts (ACF) (9.3 +/- 0.88 vs. 6.3 +/- 0.65),
      and macroscopic tumors (3.8 +/- 0.95 vs. 2.0 +/- 0.25) compared to mice on a
      control diet. In AOM mice fed the high butterfat diet, carnitine supplementation
      inhibited ACF (4.9 +/- 0.7 vs. 9.3 +/- 0.88, P < 0.001), crypt multiciplicity
      (1.6 +/- 0.08 vs. 1.92 +/- 0.1, P < 0.01) and tumors (1.5 +/- 0.38 vs. 3.8 +/-
      0.95, P < 0.001). Carnitine supplementation resulted in significantly increased
      tissue carnitine and acylcarnitine levels. Carnitine inhibited the development of
      precancerous lesions and macroscopic colonic tumors in AOM-treated mice. However,
      carnitine did not exert protective effects on intestinal tumors in Apc (Min/+)
      mice.

PMID- 23163857
TI  - The association between milk consumption and bladder cancer risk: appraisal of a
      recent meta-analysis.

PMID- 23163860
TI  - Arecoline-stimulated placenta growth factor production in gingival epithelial
      cells: modulation by curcumin.
AB  - OBJECTIVE: Placenta growth factor (PlGF) is associated with the progression and
      prognosis of oral cancer. MATERIALS AND METHODS: This study used ELISA,
      quantitative polymerase chain reaction, and Western blotting to study the
      arecoline-stimulated (PlGF) protein or mRNA expression in human gingival
      epithelial S-G cells. RESULTS: Arecoline, a major areca nut alkaloid and an oral
      carcinogen, could stimulate PlGF protein synthesis in S-G cells in a dose- and
      time-dependent manner. The levels of PlGF protein secretion increased about 3.1-
      and 3.8-fold after 24-h exposure to 0.4 and 0.8 mM arecoline, respectively.
      Pretreatment with antioxidant N-acetyl-l-cysteine (NAC) and ERK inhibitor
      PD98059, but not NF-kappaB inhibitor Bay 11-7082, JNK inhibitor SP600125, p38
      MAPK inhibitor SB203580, and PI3-K inhibitor LY294002, significantly reduced
      arecoline-induced PlGF protein synthesis. ELISA analyses demonstrated that NAC
      and PD98059 reduced about 43% and 38% of the arecoline-induced PlGF protein
      secretion, respectively. However, combined treatment with NAC and PD98059 did not
      show additive effect. Moreover, 10 MUM curcumin and 4 mM NAC significantly
      inhibited arecoline-induced ERK activation. Furthermore, 10 MUM curcumin
      completely blocked arecoline-induced PlGF mRNA expression. CONCLUSION: Arecoline
      induced PlGF synthesis is probably mediated by reactive oxygen species/ERK
      pathways, and curcumin may be an useful agent in controlling oral carcinogenesis.

PMID- 23163862
TI  - Nano and molecular science and technology special issue honoring Paul Barbara.

PMID- 23163863
TI  - A NEW RESTORATIVE TECHNIQUE FOR THE PERISHING IMPLANT DUE TO ABUTMENT SCREW
      FRACTURE.
AB  - Abstract   Abutment screw fracture, although uncommon, occurs in clinical
      practice. In many cases, the fractured end can be retrieved and replaced by a new
      abutment screw. However, sometimes the screw cannot be removed conservatively. By
      using rotary instruments, internal threads of the screw hole may be damaged and
      the implant rendered useless. To overcome these problems, this article presents a
      technique of converting the screw chamber into post space and rehabilitating with
      the new crown over this post and core system.

PMID- 23163864
TI  - Medication use among inflammatory bowel disease patients: excessive consumption
      of antidepressants and analgesics.
AB  - OBJECTIVE: Little is known about differences in the use of medications between
      inflammatory bowel disease (IBD) patients and the general population. The aims of
      this study were to observe those differences and to discuss reasons for them. The
      relation between medication use and HRQoL of IBD patients was examined. MATERIAL
      AND METHODS: The use of prescribed medication of 2831 IBD patients and 5662
      control subjects were scrutinized and compared by utilizing a national
      reimbursement register. Annual costs and number of defined daily doses (DDD) of
      medications were calculated. The relationship between medications and health
      related quality of life (HRQoL) of IBD patients was examined by using a postal
      questionnaire including a generic (15D) and a disease-specific (IBDQ) HRQoL tool.
      The questionnaire also included demographic questions and questions about IBD
      patients' use of biological medications. RESULTS: Use of antidepressants (OR:
      1.44, 95% CI: 1.28-1.61), anxiolytics (OR: 1.52, 95% CI: 1.31-1.78), oral
      bisphosphonates (OR: 6.08, 95% CI: 4.56-8.11), cardiovascular medications (OR:
      1.38, 95% CI: 1.24-1.54), antibiotics (OR: 4.01, 95% CI: 3.57-4.51), proton pump
      inhibitors (OR: 3.90, 95% CI: 3.48-4.36), and nonsteroidal anti-inflammatory
      analgesics (OR: 1.17, 95% CI: 1.07-1.28) was significantly more common in IBD
      than among the controls. Those who used antidepressants, anxiolytics, or
      analgesics had significantly impaired HRQoL (p < 0.001). CONCLUSIONS: IBD
      patients and general population differ in terms of their medicine use in many
      respects, and especially use of analgesics and antidepressants is more common
      among IBD patients. Use of antidepressants, anxiolytics, and analgesics was
      related to impaired HRQoL.

PMID- 23163865
TI  - B*07:156, revealed by sequence-based typing of a leukemia patient and confirmed
      by allele-specific amplification.
AB  - We present the full-length sequence of the novel allele HLA-B*07:156, closely
      related to B*07:02:01.

PMID- 23163866
TI  - The fate of being forgotten: information that is initially forgotten is judged as
      less important.
AB  - Is forgotten information deemed less important than remembered information? The
      present study examined potential biases regarding the importance of information
      that was initially forgotten. In Experiment 1 participants studied words paired
      with varying point values that denoted their importance and were encouraged to
      recall higher value words. Participants recalled more high-value words on an
      initial test. However, on a later cued recall test for the values, initially
      forgotten words were rated as less valuable than remembered words. Experiment 2
      used a similar procedure with the exception that participants rated the
      importance of traits when evaluating a significant other (e.g., honest,
      intelligent). Participants were more likely to recall highly valued traits but
      regarded forgotten traits as less valuable than remembered traits. These results
      suggest that a forgetting bias exists: If information is initially forgotten, it
      is later deemed as less important.

PMID- 23163867
TI  - Presternal dermoid cyst mimicking lymphatic malformation: a case report and
      review of the literature.
AB  - We describe an 11-month-old boy with an unusually large presternal mass present
      since birth. The large size, fluctuant properties, transillumination,
      compressibility, and imaging of this lesion were characteristic of a lymphatic
      malformation. Although four treatments with sclerotherapy markedly reduced its
      size, it was not until definitive treatment with surgical excision and the final
      pathology report that we arrived at the ultimate diagnosis of dermoid cyst.
      Dermoid cysts, although appearing along embryologic lines of closure, are rarely
      presternal. They are usually small, thick walled, and filled with sebaceous or
      keratinous fluid, which typically allows for clinical diagnosis, and show
      characteristic features on magnetic resonance imaging (MRI) and ultrasound.
      However, this case illustrates that dermoid cysts can appear in somewhat atypical
      locations, and imaging is not always diagnostic, so dermoid cyst should remain a
      part of the differential diagnosis for any lesion presenting midsternally,
      regardless of the size and imaging characteristics.

PMID- 23163868
TI  - Bill Costerton: leader as servant.

PMID- 23163869
TI  - Structural, serological, and genetic characterization of the O-antigen of
      Providencia alcalifaciens O40.
AB  - The O-polysaccharide chain of the lipopolysaccharide (O-antigen) on the bacterial
      cell surface is one of the most structurally variable cell components and serves
      as a basis for serotyping of Gram-negative bacteria, including human
      opportunistic pathogens of the genus Providencia. In this work, the O-antigen of
      Providencia alcalifaciens O40 was obtained by mild acid degradation of the
      isolated lipopolysaccharide and studied by chemical methods and high-resolution
      NMR spectroscopy. The following structure of the O-polysaccharide was
      established: ->4)-beta-D-Quip3NFo-(1->3)-alpha-D-Galp-(1->3)-beta-D-GlcpA-(1->3)
      beta-D-GalpNAc-(1->, where GlcA stands for glucuronic acid and Qui3NFo for 3,6
      dideoxy-3-formamidoglucose. The O40-antigen was found to be structurally and
      serologically related to the O-antigens of P. alcalifaciens O5 and Providencia
      stuartii O18. The O40-antigen gene cluster between cpxA and yibK was sequenced,
      and the gene functions were predicted in silico. In agreement with the O
      polysaccharide structure established, the genes for the synthesis of dTDP-D
      Qui3NFo, UDP-D-Gal, UDP-D-GlcA, and UDP-D-GalNAc as well as those encoding three
      glycosyltransferases, flippase (Wzx), and O-antigen polymerase (Wzy) were
      recognized. In addition, homologues of wza, wzb, and wzc genes, which are
      required for the surface expression of capsular polysaccharides, were found
      within the gene cluster, suggesting that the O-polysaccharide studied is a part
      of the capsule-related form of the lipopolysaccharide called K(LPS).

PMID- 23163870
TI  - Improved diagnostic power by combined interferon-gamma release assay and nested
      PCR in tuberculous pleurisy in high tuberculosis prevalence area.
AB  - The conventional acid fast bacilli (AFB) smear and Mycobacterium tuberculosis
      (M.tb) culture of pleural effusion and tuberculin skin test (TST) in tuberculous
      pleurisy are unable to meet clinical needs because of their low sensitivities and
      specificities. To evaluate the diagnostic accuracies of QuantiFERON TB Gold In
      Tube test (QFT-GIT) and nested-PCR in tuberculous pleurisy, we conducted a cross
      sectional study in regions of China with a high tuberculosis (TB) epidemic.
      Seventy-eight participants were enrolled: 58 TB patients with diagnosis of
      confirmed or probable tuberculous pleurisy and 20 non-TB patients with a
      diagnosis of other non-TB diseases. The positive rates of AFB smear and M.tb
      culture in the pleural effusion were 5.8% (2/42) and 10.6% (5/47), respectively.
      The sensitivity and specificity of QFT-GIT were 93.1% (54/58) and 90.0% (18/20),
      whereas those of TST were 68.5% (37/54) and 86.7% (13/15), respectively; the
      sensitivity of QFT-GIT was significantly higher than TST (P = 0.013). The
      sensitivity and specificity of M.tb-specific nested-PCR in pleural effusion were
      94.8% (55/58) and 90.0% (18/20), respectively, with a turnaround time of 7 h.
      Furthermore, combined QFT-GIT and nested-PCR detection improves the specificity
      to 100% with a sensitivity of up to 90.0%. This combination of immunoassay and
      molecular detection holds promise for the clinical diagnosis of tuberculous
      pleurisy.

PMID- 23163871
TI  - Human intestinal epithelial cell-derived molecule(s) increase enterohemorrhagic
      Escherichia coli virulence.
AB  - To better understand the role of host cell-derived molecules on enterohemorrhagic
      Escherichia coli (EHEC) infection, we studied EHEC virulence gene expression when
      exposed to cell-free spent (conditioned) medium (CM) from HCT-8 intestinal
      epithelial cells. Exposure to HCT-8 CM for 1 h and 3 h increased the expression
      of 32 of 41 EHEC locus of enterocyte effacement (LEE) virulence genes compared
      with fresh medium (FM). Expression of the Shiga toxin 1 (stx1B) gene was up
      regulated at 1 h of exposure. Seventeen genes encoded by prophage 933W, including
      those for Stx2, were also up-regulated at both time-points. The increase in 933W
      prophage expression was mirrored by a 2.7-fold increase in phage titers.
      Consistent with the increase in virulence gene expression, we observed a fivefold
      increase in EHEC attachment to epithelial cells when exposed to CM. The increase
      in EHEC attachment was abolished when CM was heated to 95  degrees C or treated
      with proteinase K to degrade the proteins. The host cell-derived molecule(s) were
      larger than 3 kDa, which suggests that the molecule(s) that increase EHEC
      virulence and attachment are protein-based.

PMID- 23163872
TI  - Alcohol treatment enhances Staphylococcus aureus biofilm development.
AB  - Staphylococcus aureus forms pathogenic biofilms. Previous studies have indicated
      that ethanol supplementation during S. aureus biofilm formation results in
      increased biofilm formation and changes in gene expression. However, the impact
      of alcohols on preformed S. aureus biofilms has not been studied. In this study,
      we formed S. aureus biofilms on PVC plastic plates and then treated these
      preformed biofilms with five different alcohols. We observed that alcohol
      treatment of preformed S. aureus biofilms led to significant increases in biofilm
      levels after 24 h of treatment. Many bacteria within these biofilms were found to
      be alive and metabolically active. Alcohol treatment also resulted in increased
      transcription of the biofilm-promoting genes icaA and icaD, as well as several
      antibiotic resistance genes. These results demonstrate that treatment of S.
      aureus preformed biofilms with alcohols enhances biofilm levels if maintained for
      extended periods. Thus, alcohols might be of limited usefulness for the
      eradication of preformed S. aureus biofilms.

PMID- 23163873
TI  - Immunogenicity and therapeutic effects of Ag85A/B chimeric DNA vaccine in mice
      infected with Mycobacterium tuberculosis.
AB  - The situation of tuberculosis (TB) is very severe in China. New therapeutic
      agents or regimens to treat TB are urgently needed. In this study, Mycobacterium
      tuberculosis-infected mice were given immunotherapy intramuscularly with Ag85A/B
      chimeric DNA or saline, plasmid vector pVAX1, or Mycobacterium vaccae vaccine.
      The mice treated with Ag85A/B chimeric DNA showed significantly higher numbers of
      T cells secreting interferon-gamma (IFN-gamma), more IFN-gamma in splenocyte
      culture supernatant, more Th1 and Tc1 cells, and higher ratios of Th1/Th2 and
      Tc1/Tc2 cells in whole blood, indicating a predominant Th1 immune response to
      treatment. Infected mice treated with doses of 100 MUg Ag85A/B chimeric DNA had
      an extended time until death of 50% of the animals that was markedly longer than
      the saline and vector control groups, and the death rate at 1 month after the
      last dose was lower than that in the other groups. Compared with the saline
      group, 100 MUg Ag85A/B chimeric DNA and 100 MUg Ag85A DNA reduced the pulmonary
      bacterial loads by 0.79 and 0.45 logs, and the liver bacterial loads by 0.52 and
      0.50 logs, respectively. Pathological changes in the lungs were less, and the
      lesions were more limited. These results show that Ag85A/B chimeric DNA was
      effective for the treatment of TB, significantly increasing the cellular immune
      response and inhibiting the growth of M. tuberculosis.

PMID- 23163874
TI  - Mannose receptor, C type 1 contributes to bacterial uptake by placental
      trophoblast giant cells.
AB  - During pregnancy, maternal immune function is strictly controlled and immune
      tolerance is induced. Trophoblast giant (TG) cells exhibit phagocytic activity
      and show macrophage-like activity against microorganisms in the placenta.
      However, details of molecular receptors and mechanisms for uptake by TG cells
      have not been clarified. In this study, we investigated the involvement of the
      mannose receptor, C type 1 (MRC1), in the uptake of the abortion-inducible
      bacterium Listeria monocytogenes and abortion-uninducible bacteria Bacillus
      subtilis and Escherichia coli by TG cells differentiated from a mouse trophoblast
      stem cell line in vitro. Knockdown of MRC1 inhibited the uptake of all of these
      bacteria, as did the blocking of MRC1 by MRC1 ligands. The uptake of bacteria by
      MRC1 delayed the maturation of phagolysosomes. These findings suggest that MRC1
      plays an important role in the uptake of various bacteria by TG cells and may
      provide an opportunity for those bacteria to escape from phagosomes.

PMID- 23163876
TI  - Highly durable double sol-gel layer ratiometric fluorescent pH optode based on
      the combination of two types of quantum dots and absorbing pH indicators.
AB  - Long-term stable ratiometric fluorescent optical pH sensors (optodes) based on
      double sol-gel silica layers are prepared with the first layer embedding two
      types of quantum dots (QDs) and the second layer embedding light-absorbing pH
      indicators. The sensors are fabricated by a simple general sol-gel spin-coating
      method. The resulting double-layer pH optodes are designed as having long Stokes
      shift as well as ratiometric fluorescence emission response to pH in aqueous
      solutions of varying pH values. This optode has high durability against
      continuous light exposure, even under severe acidic condition (1 M HCl), and the
      storage stability is over a period of more than 6 months. These results indicate
      that the double-layer ratiometric fluorescence-based pH optode allows for long
      term pH sensing. When two pH indicators of different pK(a) values with an
      optimized mixing ratio are embedded into the second layer, a double-layer pH
      optode with reproducible linear response in a wide pH range of over 6 pH units
      (from pH 4 to 10) can be designed and fabricated.

PMID- 23163875
TI  - Pluronic P85 enhances the efficacy of outer membrane vesicles as a subunit
      vaccine against Brucella melitensis challenge in mice.
AB  - Brucellosis is the most common zoonotic disease worldwide, and there is no
      vaccine for human use. Brucella melitensis Rev1, a live attenuated strain, is the
      commercial vaccine for small ruminants to prevent B. melitensis infections but
      has been associated with abortions in animals. Moreover, strain Rev1 is known to
      cause disease in humans and cannot be used for human vaccination. Outer membrane
      vesicles (OMVs) obtained from B. melitensis have been shown to provide protection
      similar to strain Rev1 in mice against B. melitensis challenge. In the present
      work, we tested the efficacy of Pluronic P85 as an adjuvant to enhance the
      efficacy of Brucella OMVs as a vaccine. P85 enhanced the in vitro secretion of
      TNF-alpha by macrophages induced with OMVs and P85. Further, P85 enhanced the
      protection provided by OMVs against B. melitensis challenge. This enhanced
      protection was associated with higher total IgG antibody production but not
      increased IFN-gamma or IL-4 cytokine levels. Moreover, P85 alone provided
      significantly better clearance of B. melitensis compared to saline-vaccinated
      mice. Further studies are warranted to find the mechanism of action of P85 that
      provides nonspecific protection and enhances the efficacy of OMVs as a vaccine
      against B. melitensis.

PMID- 23163877
TI  - Detection of cerebral hyperperfusion syndrome after carotid endarterectomy with
      CT perfusion.
AB  - We present the case of a 60-year-old female patient, who developed symptomatic
      internal carotid artery stenosis and subsequently underwent carotid
      endarterectomy. Four days after an uneventful surgery the patient developed
      confusion, seizures, and was admitted to the ICU. CT perfusion revealed reduced
      ispilateral time-to-peak and mean-transient-time and increased cerebral blood
      volume and cerebral blood flow, confirming the diagnosis of cerebral
      hyperperfusion syndrome. We thus propose CT perfusion as a diagnostic means for
      cerebral hyperperfusion syndrome, a syndrome that remains underdiagnosed. 

PMID- 23163878
TI  - Highly regioselective C-N bond formation through C-H azolation of indoles
      promoted by iodine in aqueous media.
AB  - An efficient and metal-free method for the direct C-N coupling of indoles with
      azoles to produce 2-(azol-1-yl)indoles in aqueous solution has been developed.
      This reaction proceeded highly regioselectively to provide a variety of indole
      derivatives with good to excellent yields.

PMID- 23163879
TI  - Divergent cyclizations of 1-R-ethynyl-9,10-anthraquinones: use of thiourea as a
      "S2-" equivalent in an "anchor-relay" addition mediated by formal C-H activation.
AB  - The EtONa-mediated reaction of peri-R-ethynyl-9,10-anthraquinones with thiourea
      yields 2-R-7H-dibenzo[de,h]quinolin-7-ones and 2-R-anthra[2,1-b]thiophene-6,11
      diones. Although 2-R-7H-dibenzo[de,h]quinolin-7-ones were observed previously in
      reactions with other N-centered nucleophiles (hydrazine, guanidine, and urea),
      the formation of 2-R-anthra[2,1-b]thiophene-6,11-diones is a new reactivity path.
      DFT computations analyzed factors responsible for the switch in reactivity and
      the relative importance of two possible pathways: (1) the "anchor-relay"
      mechanism mediated by nucleophilic attack at the carbonyl and (2) direct attack
      at the alkyne. The two pathways converge on a vinyl sulfur anion, set up for a 5
      endo-trig cyclization at the ortho-position. Subsequent rearomatization/oxidation
      provides the fused thiophene product via formal C-H activation. The calculations
      suggest that the latter pathway, the direct attack at the alkyne, is more likely,
      due to the relatively high barrier for the 8-endo-dig cyclization (pathway 1).
      Computational insights led to a more selective synthesis of fused thiophenes,
      based on the reaction of acetylenic anthraquinones with sodium sulfide. This
      reaction does not require prefunctionalization at the ortho-position since direct
      C-H activation is efficient. The absence of fused five-membered heterocycles in
      earlier work was investigated computationally. The other N-centered nucleophiles
      form stronger anion-pi complexes with the electron-deficient quinone core,
      promoting carbonyl attack over direct alkyne attack.

PMID- 23163880
TI  - Efficacy and safety of ipragliflozin in patients with type 2 diabetes
      inadequately controlled on metformin: a dose-finding study.
AB  - AIMS: Ipragliflozin is a novel, selective inhibitor of sodium glucose co
      transporter 2 (SGLT2 inhibitor) in clinical development for type 2 diabetes
      mellitus (T2DM) treatment. This study assessed the efficacy and safety of
      different doses of ipragliflozin. METHODS: In a 12-week, multicentre, double
      blind, randomized, placebo-controlled, dose-finding study patients with
      inadequate glycaemic control on metformin monotherapy (>=1500 mg/day) were
      randomized to one of four ipragliflozin treatment groups (12.5, 50, 150 or 300 mg
      once daily) or placebo. Primary efficacy outcome was mean change from baseline in
      haemoglobin A1c (HbA1c) compared to placebo at week 12. Adverse events (AEs),
      vital signs and laboratory safety measurements were assessed. RESULTS:
      Ipragliflozin dose dependently decreased HbA1c from baseline to week 12 compared
      to placebo (-0.22, -0.34, -0.40 and -0.48% for ipragliflozin 12.5, 50, 150 and
      300 mg, respectively). Decreases in body weight and blood pressure were observed
      for all ipragliflozin groups. AEs occurred in 39.7-51.4% of the ipragliflozin
      groups and 39.4% of placebo patients. Urinary tract infections (1.4-6.9 vs.
      6.1%), genital infections (0-4.3 vs. 1.5%) and hypoglycaemia (0-5.9 vs. 3.0%)
      were similar in the ipragliflozin and placebo groups, respectively, without dose
      dependency. There were no clinically relevant effects on other safety
      measurements. CONCLUSIONS: Ipragliflozin treatment improved glycaemic control
      when added to metformin therapy and may be associated with weight loss and
      reductions in blood pressure compared to placebo. No safety or tolerability
      concerns were identified at any of the tested doses supporting the further
      development of ipragliflozin at >=50 mg doses in T2DM patients.

PMID- 23163881
TI  - In vivo distribution and toxicity of PAMAM dendrimers in the central nervous
      system depend on their surface chemistry.
AB  - Dendrimers have been described as one of the most tunable and therefore
      potentially applicable nanoparticles both for diagnostics and therapy. Recently,
      in order to realize drug delivery agents, most of the effort has been dedicated
      to the development of dendrimers that could internalize into the cells and target
      specific intracellular compartments in vitro and in vivo. Here, we describe cell
      internalization properties and diffusion of G4 and G4-C12 modified PAMAM
      dendrimers in primary neuronal cultures and in the CNS of live animals. Confocal
      imaging on primary neurons reveals that dendrimers are able to cross the cell
      membrane and reach intracellular localization following endocytosis. Moreover,
      functionalization of PAMAMs has a dramatic effect on their ability to diffuse in
      the CNS tissue in vivo and penetrate living neurons as shown by intraparenchymal
      or intraventricular injections. 100 nM G4-C12 PAMAM dendrimer already induces
      dramatic apoptotic cell death of neurons in vitro. On the contrary, G4 PAMAM does
      not induce apoptotic cell death of neural cells in the sub-micromolar range of
      concentration and induces low microglia activation in brain tissue after a week.
      Our detailed description of dendrimer distribution patterns in the CNS will
      facilitate the design of tailored nanomaterials in light of future clinical
      applications.

PMID- 23163882
TI  - Failure to detect an association between aggressive periodontitis and the
      prevalence of herpesviruses.
AB  - BACKGROUND: Herpes simplex virus type 1 (HSV-1), human cytomegalovirus (HCMV) and
      Epstein-Barr virus (EBV) have been suspected to play a causal role in
      periodontitis pathogenesis. The aim of this study was to determine the prevalence
      of these viruses in subgingival plaque samples of Caucasian patients with
      generalized aggressive periodontitis compared to periodontally healthy controls.
      METHODS: A total of 65 patients with aggressive periodontitis and 65 unmatched
      controls from Germany were investigated in the study. Subgingival plaque samples
      were analysed for the presence of HSV-1, EBV and HCMV by quantitative real-time
      polymerase chain reaction assays. Viral antibody titres were determined
      quantitatively by immunosorbent assays. RESULTS: DNA of HSV-1 and HCMV were
      detected in 1.5% of the patients and controls, whereas EBV DNA was present in
      10.8% and 13.9% respectively. Detection rates of serum IgG against HSV-1 (76.1%
      versus 73.9%), EBV (98.5% versus 96.9%), HCMV (47.7% versus 46.2%) and IgM levels
      against HSV-1 (6.2% versus 1.5%), EBV (0% versus 0%), HCMV (0% versus 1.5%) did
      not significantly differ between patients and controls. CONCLUSION: The data of
      our study do not suggest any contribution of HSV-1, EBV or HCMV to aggressive
      periodontitis in a German population. Ethnic and methodological aspects might
      have caused conflicting results of previous studies.

PMID- 23163883
TI  - The exocyst complex contributes to PIN auxin efflux carrier recycling and polar
      auxin transport in Arabidopsis.
AB  - In land plants polar auxin transport is one of the substantial processes guiding
      whole plant polarity and morphogenesis. Directional auxin fluxes are mediated by
      PIN auxin efflux carriers, polarly localized at the plasma membrane. The
      polarization of exocytosis in yeast and animals is assisted by the exocyst: an
      octameric vesicle-tethering complex and an effector of Rab and Rho GTPases. Here
      we show that rootward polar auxin transport is compromised in roots of
      Arabidopsis thaliana loss-of-function mutants in the EXO70A1 exocyst subunit. The
      recycling of PIN1 and PIN2 proteins from brefeldin-A compartments is delayed
      after the brefeldin-A washout in exo70A1 and sec8 exocyst mutants. Relocalization
      of PIN1 and PIN2 proteins after prolonged brefeldin-A treatment is largely
      impaired in these mutants. At the same time, however, plasma membrane
      localization of GFP:EXO70A1, and the other exocyst subunits studied (GFP:SEC8 and
      YFP:SEC10), is resistant to brefeldin-A treatment. In root cells of the exo70A1
      mutant, a portion of PIN2 is internalized and retained in specific, abnormally
      enlarged, endomembrane compartments that are distinct from VHA-a1-labelled early
      endosomes or the trans-Golgi network, but are RAB-A5d positive. We conclude that
      the exocyst is involved in PIN1 and PIN2 recycling, and thus in polar auxin
      transport regulation.

PMID- 23163884
TI  - Serotypes and virulence profiles of atypical enteropathogenic Escherichia coli
      (EPEC) isolated from bovine farms and abattoirs.
AB  - AIMS: The objective of this study was to examine the prevalence of
      enteropathogenic Escherichia coli (EPEC) on beef and dairy farms and in beef
      abattoirs and to characterize the isolates in terms of serogroup and virulence
      markers. METHODS AND RESULTS: Bovine faecal samples (n = 1200), farm soil samples
      (n = 600), hide samples (n = 450) and carcass samples (n = 450) were collected
      from 20 farms and three abattoirs throughout Ireland over a 12-month period.
      After selective enrichment, samples testing positive for the intimin gene (eae)
      using PCR screening were cultured, and colonies were examined for the presence of
      the eae, vt(1) and vt(2) genes. Colonies that were positive for the intimin gene
      and negative for the verotoxin genes were further screened using PCR for a range
      of virulence factors including tir, espA, espB katP, espP, etpD, saa, sab, toxB,
      iha, lpfA(O157/OI-141) , lpfA(O113) and lpfA(O157/OI-154) . PCR screening was
      also used to screen for variations in the intimin gene (eae). Of the 2700 source
      samples analysed, 3.9% (47 of 1200) of faecal, 2% (12 of 600) of soil, 6.4% (29
      of 450) of hide and 0.7% (3 of 450) of carcass samples were PCR positive (for the
      presence of the eae gene). All 140 isolates obtained were atypical EPEC (aEPEC),
      while theta and beta intimin types were common. The virulence factors hlyA, tir,
      lpfA (O113) , lpfA (O157/OI-154) , and iha were frequently detected, while
      lpfA(O157/OI-141) , saa, espA, espB and toxB were also present but to a lesser
      extent. CONCLUSIONS: It was concluded that cattle are a source of aEPEC, many of
      which have the virulence machinery necessary to be pathogenic to humans.
      SIGNIFICANCE AND IMPACT OF THE STUDY: These findings suggest the need for
      increased research on aEPEC with particular emphasis on food safety and public
      health risk.

PMID- 23163885
TI  - The clinical utility of an SCN1A genetic diagnosis in infantile-onset epilepsy.
AB  - AIM: Genetic testing in the epilepsies is becoming an increasingly accessible
      clinical tool. Mutations in the sodium channel alpha 1 subunit (SCN1A) gene are
      most notably associated with Dravet syndrome. This is the first study to assess
      the impact of SCN1A testing on patient management from both carer and physician
      perspectives. METHOD: Participants were identified prospectively from referrals
      to the Epilepsy Genetics Service in Glasgow and contacted via their referring
      clinicians. Questionnaires exploring the consequences of SCN1A genetic testing
      for each case were sent to carers and physicians. RESULTS: Of the 244 individuals
      contacted, 182 (75%) carried a SCN1A mutation. Carers of 187 (77%) patients
      responded (90 females, 97 males; mean age at referral 4 y 10 mo; interquartile
      range 9 y 1 mo). Of those participants whose children tested positive for a
      mutation, 87% reported that genetic testing was helpful, leading to treatment
      changes resulting in fewer seizures and improved access to therapies and respite
      care. Out of 187 physicians, 163 responded (87%), of whom 48% reported that a
      positive test facilitated diagnosis earlier than with clinical and
      electroencephalography data alone. It prevented additional investigations in 67%
      of patients, altered treatment approach in 69%, influenced medication choice in
      74%, and, through medication change, improved seizure control in 42%.
      INTERPRETATION: In addition to confirming a clinical diagnosis, a positive SCN1A
      test result influenced treatment choice and assisted in accessing additional
      therapies, especially in the very young.

PMID- 23163886
TI  - Relationship of symptom duration and fecal bacteriotherapy in Clostridium
      difficile infection-pooled data analysis and a systematic review.
AB  - OBJECTIVE: Clostridium difficle-associated infection (CDI) is usually treated
      with antibiotics; nevertheless, the infection has a high relapse rate. Case
      series and case reports using fecal microbiota transplant (FMT) for CDI show
      promising results. However, there are no large studies to provide evidence for
      the efficacy of this therapy. The aim of this pooled patient data meta-analysis
      was to determine the efficacy of FMT in CDI. METHODS: We performed a literature
      search for FMT for CDI or pseudomembranous colitis. Individual patient data were
      obtained from each study. The primary endpoint was to assess the rate of diarrhea
      resolution. Secondary endpoints were to identify variables associated with
      treatment failure and side effects of therapy. RESULTS: A total of 289 patients
      from 25 published articles who received FMT for CDI were included in the pooled
      data analysis. FMT had an overall success rate of 91.2%. On univariate analysis,
      shorter duration of symptoms before FMT (< 60 days) and gastroduodenal route of
      fecal instillation were associated with treatment failure. On multivariate
      regression analysis, shorter duration of symptoms (< 60 days) before the FMT (OR=
      11.08; p = 0.0009) was associated with treatment failure. Reported adverse events
      following FMT were irritable bowel syndrome (n = 1), symptoms of mild enteritis
      (n = 3), and suspected peritonitis following the procedure (n = 1). CONCLUSION:
      FMT is a safe and effective treatment option for CDI. Shorter duration of
      symptoms (< 60 days) before administering FMT is associated with treatment
      failure.

PMID- 23163887
TI  - Crystal structures of HIV-1 reverse transcriptase with picomolar inhibitors
      reveal key interactions for drug design.
AB  - X-ray crystal structures at 2.9 A resolution are reported for two complexes of
      catechol diethers with HIV-1 reverse transcriptase. The results help elucidate
      the structural origins of the extreme antiviral activity of the compounds. The
      possibility of halogen bonding between the inhibitors and Pro95 is addressed.
      Structural analysis reveals key interactions with conserved residues P95 and W229
      of importance for design of inhibitors with high potency and favorable resistance
      profiles.

PMID- 23163888
TI  - Association of CD28 and CTLA-4 gene polymorphisms with aggressive periodontitis
      in Brazilians.
AB  - OBJECTIVE: Susceptibility to and severity of periodontal disease is influenced by
      gene polymorphisms related to the immune response. Co-stimulatory molecules, such
      as CD28 and CTLA-4, are critical in the development of such responses. Our
      hypothesis is that polymorphisms in genes that code for these molecules may be
      associated with periodontitis. The aim of the study was to investigate the
      association between +17 (T/C) CD28 and +49 (A/G) CTLA-4 gene polymorphisms and
      periodontitis in Brazilians. MATERIALS AND METHODS: Genomic DNA was obtained from
      oral swabs of 424 individuals categorized into three groups (control group,
      aggressive, and chronic periodontitis) considering clinical parameters such as
      probing depth and clinical attachment loss. The genotyping was performed by
      polymerase chain reaction-restriction fragment length polymorphism. RESULTS:
      There was an association between the T(-) genotype of the CD28 polymorphism and
      aggressive periodontitis (P = 0.04). Moreover, the A(+) genotype for CTLA-4 was
      associated with greater clinical attachment loss in non-smokers with aggressive
      periodontitis (P = 0.006, OR = 16.25, CI = 2.25-117.11). CONCLUSIONS: These
      findings show that T(-) in CD28 + 17 (T/C) and the A(+) in CTLA-4 +49 (A/G)
      genotypes are associated with susceptibility to aggressive periodontal disease.
      Thus, our study highlights these polymorphisms as potential genetic
      susceptibility markers of periodontitis in Brazilians.

PMID- 23163889
TI  - Superparamagnetic iron oxide-enhanced interstitial magnetic resonance
      lymphography to detect a sentinel lymph node in tongue cancer patients.
AB  - CONCLUSION: This is the first report on human sentinel node (SN) detection by
      interstitial magnetic resonance (MR) lymphography with superparamagnetic iron
      oxide (SPIO) in tongue cancer patients who also underwent lymphoscintigraphy. Our
      results indicate that further studies are warranted, as this novel method may
      replace current scintigraphic techniques. OBJECTIVES: To examine the feasibility
      of interstitial MR lymphography using SPIO for SN detection in the head and neck
      region. METHODS: MR images were acquired sequentially at 10 min, 30 min, and 24 h
      after submucosally injecting 0.1 ml SPIO (ferucarbotran) around the tumor in
      three patients with tongue cancer without cervical lymph node metastasis
      (clinical T2N0M0). RESULTS: The SNs were clearly visualized in the 10 min
      interstitial MR lymphography images and were completely concordant with those
      visualized by (99m)Tc-radiocolloid lymphoscintigraphy and a gamma probe in all
      cases. Iron incorporation into the SNs was confirmed by pathological examination.

PMID- 23163890
TI  - The midline electroneurography method for facial palsy reflects total nerve
      degeneration.
AB  - CONCLUSION: The midline electroneurography (ENoG) method might reflect total
      facial nerve degeneration. OBJECTIVE: We compared ENoG values in patients with
      facial palsy using two different methods, the midline method and five
      electroneurogram recordings, to reveal whether the ENoG value obtained with the
      midline method reflects total facial nerve degeneration. METHODS: Forty patients
      with facial palsy were enrolled. Compound muscle action potentials (CMAPs) were
      recorded using the midline method, in which the anode was placed on the mental
      protuberance and the cathode was placed on the philtrum. Additionally, five
      electroneurogram recordings were obtained by placing the anode on the skin of the
      parietal region and five cathodes on the skin over five facial muscles
      (frontalis, orbicularis oculi, nasalis, orbicularis oris, and depressor anguli
      oris muscles). ENoG values recorded using the two methods were compared. RESULTS:
      The ENoG values of the five facial muscles did not differ from those obtained
      using the midline method. The total ENoG value calculated by summing five CMAPs
      from five facial muscles, which is considered to reflect total facial nerve
      degeneration, was not significantly different from that using midline methods;
      moreover, a strong positive correlation coefficient (r = 0.87) was found between
      them.

PMID- 23163891
TI  - Genetic analysis of PAX3 for diagnosis of Waardenburg syndrome type I.
AB  - CONCLUSION: PAX3 genetic analysis increased the diagnostic accuracy for
      Waardenburg syndrome type I (WS1). Analysis of the three-dimensional (3D)
      structure of PAX3 helped verify the pathogenicity of a missense mutation, and
      multiple ligation-dependent probe amplification (MLPA) analysis of PAX3 increased
      the sensitivity of genetic diagnosis in patients with WS1. OBJECTIVES: Clinical
      diagnosis of WS1 is often difficult in individual patients with isolated, mild,
      or non-specific symptoms. The objective of the present study was to facilitate
      the accurate diagnosis of WS1 through genetic analysis of PAX3 and to expand the
      spectrum of known PAX3 mutations. METHODS: In two Japanese families with WS1, we
      conducted a clinical evaluation of symptoms and genetic analysis, which involved
      direct sequencing, MLPA analysis, quantitative PCR of PAX3, and analysis of the
      predicted 3D structure of PAX3. The normal-hearing control group comprised 92
      subjects who had normal hearing according to pure tone audiometry. RESULTS: In
      one family, direct sequencing of PAX3 identified a heterozygous mutation, p.I59F.
      Analysis of PAX3 3D structures indicated that this mutation distorted the DNA
      binding site of PAX3. In the other family, MLPA analysis and subsequent
      quantitative PCR detected a large, heterozygous deletion spanning 1759-2554 kb
      that eliminated 12-18 genes including a whole PAX3 gene.

PMID- 23163892
TI  - Molecular typing of vancomycin-resistant Enterococcus faecium with an automated
      repetitive sequence-based PCR microbial typing system compared with pulsed-field
      gel electrophoresis and multilocus sequence typing.
AB  - BACKGROUND: Pulsed-field gel electrophoresis (PFGE) is the main typing method
      used for the molecular typing of vancomycin-resistant Enterococcus faecium
      (VREfm). However, more rapid and unambiguous typing methods are needed.
      DiversiLab, a repetitive sequence-based PCR (rep-PCR), offers an alternative
      method for strain typing. METHODS: Thirty-nine VREfm isolates with known
      epidemiological relationships were characterized by semi-automated rep-PCR
      (DiversiLab), PFGE, and multilocus sequence typing (MLST). RESULTS: The
      DiversiLab results were analysed in 2 ways: first relying solely on the
      DiversiLab software, and second by DiversiLab analysis combined with manual
      interpretation. The analysis with interpretation yielded more DiversiLab
      profiles, correlated better with PFGE and MLST, and grouped the isolates better
      according to their relatedness in time and space. However, most of the DiversiLab
      groups also included isolates with different PFGE and MLST types. CONCLUSIONS:
      DiversiLab provides rapid information when investigating a potential hospital
      outbreak. However, the interpretation of E. faecium DiversiLab results cannot be
      fully automated and is not always straightforward. Other typing methods may be
      necessary to confirm the analysis.

PMID- 23163893
TI  - Aeromonas caviae is the most frequent pathogen amongst cases of Aeromonas
      bacteremia in Japan.
AB  - BACKGROUND: Aeromonas species can cause various infections including bacteremia,
      gastroenteritis, cholangitis, and wound infections. To date, most studies on
      Aeromonas species have been reported from countries other than Japan. The aim of
      this study, therefore, was to evaluate Aeromonas bacteremia in Japan. METHODS: We
      reviewed the medical records of patients with Aeromonas bacteremia from January
      1994 to December 2010 in Toranomon Hospital, Tokyo, and Toranomon Hospital
      Kajigaya, Kanagawa, Japan. RESULTS: Thirty-six cases of Aeromonas bacteremia were
      identified. Of these 36 strains, 18 were Aeromonas caviae, 13 were Aeromonas
      hydrophila, and 5 were Aeromonas veronii biovar sobria. The underlying diseases
      were solid tumor (21 cases), chronic hepatic disease (13 cases), diabetes
      mellitus (9 cases), hematological malignancies (4 cases), autosomal dominant
      polycystic kidney disease (2 cases), and aplastic anemia (2 cases). Patients with
      a solid tumor more frequently presented with A. caviae bacteremia than non-A.
      caviae bacteremia (14/18 vs 7/18; p = 0.041). Additionally, 16 of the 36 episodes
      were polymicrobial, and of these, 12 had stenosis or stasis of the bile duct or
      pancreatic duct (75%). The overall 30-day mortality was 19%. CONCLUSIONS: To the
      best of our knowledge, this is the first report to identify A. caviae as the most
      frequent causative pathogen of Aeromonas bacteremia in Japan. Additionally,
      compared with previous studies, most patients in our study had solid tumors.
      These findings suggest that the characteristics of Aeromonas bacteremia vary
      among study populations.

PMID- 23163894
TI  - Circulating levels of interleukin (IL)-12 and IL-13 in Helicobacter pylori
      infected patients, and their associations with bacterial CagA and VacA virulence
      factors.
AB  - OBJECTIVE: The aim of this study was to determine the association of the
      Helicobacter pylori virulence factors, cytotoxin-associated gene A (CagA) and
      vacuolating cytotoxin A (VacA) antibodies, with serum levels of interleukin (IL)
      12 and IL-13 in H. pylori-infected duodenal ulcer (DU) patients and H. pylori
      infected asymptomatic (AS) carriers in order to elucidate any correlation between
      them. METHODS: A total of 67 DU patients, 48 AS individuals, and 26 healthy H.
      pylori-negative subjects were enrolled in this study. Serum concentrations of IL
      12 and IL-13 were determined by enzyme-linked immunosorbent assay (ELISA) method.
      Patient sera were tested by Western blot method to determine the presence of
      serum antibodies to bacterial virulence antigens p120 (CagA) and p95 (VacA).
      Serum concentrations of IL-12 and IL-13 were compared in 9 groups, including 4 AS
      phenotypes (CagA+VacA+, CagA+VacA-, CagA-VacA+, CagA-VacA-), 4 DU phenotypes
      (CagA+VacA+, CagA+VacA-, CagA-VacA+, CagA-VacA-), and 1 control group. RESULTS:
      The results revealed that DU patients positive for CagA, independent of the anti
      VacA antibody status, showed drastically elevated levels of IL-12 (251 +/- 43
      pg/ml) when compared with the other groups (p = 0.0001). No significant
      difference was found between groups regarding levels of IL-13 (p > 0.05).
      CONCLUSIONS: Our findings indicate that in the DU group, the serum concentrations
      of IL-12 but not of IL-13 were influenced by bacterial CagA, independent of the
      VacA status, suggesting that high IL-12 levels may contribute to susceptibility
      to DU in CagA-positive individuals. These findings could possibly be considered
      to improve the predictive or prognostic values of inflammatory cytokines for DU,
      and also to design possible novel therapeutic approaches.

PMID- 23163895
TI  - The pseudophosphatase MK-STYX inhibits stress granule assembly independently of
      Ser149 phosphorylation of G3BP-1.
AB  - The pseudophosphatase MK-STYX (mitogen-activated protein kinase
      phosphoserine/threonine/tyrosine-binding protein) has been implicated in the
      stress response pathway. The expression of MK-STYX inhibits the assembly of
      stress granules, which are cytoplasmic storage sites for mRNA that form as a
      protective mechanism against stressors such as heat shock, UV irradiation and
      hypoxia. Furthermore, MK-STYX interacts with a key component of stress granules:
      G3BP-1 (Ras-GTPase activating protein SH3 domain binding protein-1). Because G3BP
      1 dephosphorylation at Ser149 induces stress granule assembly, we initially
      hypothesized that the inhibition of stress granules by MK-STYX was G3BP-1
      phosphorylation-dependent. However, in the present study, using MK-STYX
      constructs and G3BP-1 phosphomimetic or nonphosphorylatable mutants, we show that
      MK-STYX inhibits stress granule formation independently of G3BP-1 phosphorylation
      at Ser149. The introduction of point mutations at the 'active site' of MK-STYX
      that convert serine and phenylalanine to histidine and cysteine, respectively, is
      sufficient to generate an active enzyme. In separate experiments, we show that
      this active mutant, MK-STYX(active), has opposite effects to wild-type MK-STYK.
      Not only does MK-STYX(active) induce stress granules, but also it has the
      capacity to dephosphorylate G3BP-1. Taken together, these results provide
      evidence that the pseudophosphatase MK-STYX plays a key role in the cellular
      response to stress.

PMID- 23163896
TI  - Stop interfering: Stroop task conflict independence from informational conflict
      and interference.
AB  - Performance of the Stroop task reflects two conflicts-informational (between the
      incongruent word and ink colour) and task (between relevant colour naming and
      irrelevant word reading). This is supported by findings showing that the anterior
      cingulate cortex is more activated by congruent and incongruent stimuli than by
      nonword neutral stimuli. Previously, researchers demonstrated behavioural
      evidence for task conflict-a reverse facilitation effect under a reduced task
      conflict control condition. The boundary conditions of this Stroop reverse
      facilitation effect are not yet clear. The current study aimed to investigate
      whether task conflict arises, and task control is needed, whenever there are two
      possible tasks, even if the irrelevant task cannot mislead one to give erroneous
      responses (i.e., stimuli do not contain an informational conflict). To this end,
      in both experiments no incongruent stimuli were presented. In Experiment 1,
      participants conducted a Stroop task with a high proportion of nonword neutrals
      and with a neutral/congruent cue in 50% of the trials. In Experiment 2, the
      nonword neutral was replaced by a real non-colour-word. We found the reverse
      facilitation effect in the noncued trials of Experiment 1. Moreover, as expected,
      this effect was eliminated when a noncolour neutral word that induced task
      conflict was used (Experiment 2). We conclude that task conflict control is
      reactively activated whenever there are at least two possible tasks, even in the
      absence of any possibility of informational conflict. 

PMID- 23163897
TI  - Extensive haplotype diversity in African American mothers and their cord blood
      units.
AB  - HLA-A, -B, -C, -DRB1, -DQB1 assignments were obtained for 374 pairs of African
      American mothers and their umbilical cord blood units (CBU) by DNA sequencing. An
      algorithm developed by the National Marrow Donor Program was used to assign 1122
      haplotypes by segregation. Seventy percent of the haplotypes carried assignments
      at all five loci. In the remainder, alleles at various loci, most often DQB1 in
      48% of the haplotypes with a missing assignment, could not be assigned due to
      sharing of both alleles by mother and CBU. There were 652 haplotypes carrying a
      unique combination of alleles at the five loci; the majority (74%) were
      singletons. Novel B~C and DRB1~DQB1 associations were observed. The results show
      the genetic diversity in this population and provide validation for a publically
      available tool for pedigree analysis. Our observations underscore the need for
      procurement of increased numbers of units in the national cord blood inventory in
      order to identify matching donors for all patients requiring hematopoietic stem
      cell transplantation.

PMID- 23163899
TI  - 4-Chloro-2-fluoro-5-nitrobenzoic acid as a possible building block for solid
      phase synthesis of various heterocyclic scaffolds.
AB  - 4-Chloro-2-fluoro-5-nitrobenzoic acid is a commercially available multireactive
      building block that can serve as a starting material in heterocyclic oriented
      synthesis (HOS) leading to various condensed nitrogenous cycles. This work
      describes its ability for the preparation of substituted nitrogenous heterocycles
      having 5-7-membered cycles via polymer-supported o-phenylendiamines.
      Immobilization of this compound on Rink resin followed by further chlorine
      substitution, reduction of a nitro group and appropriate cyclization afforded
      benzimidazoles, benzotriazoles, quinoxalinones, benzodiazepinediones and
      succinimides. The method developed is suitable for the synthesis of diverse
      libraries including the mentioned types of heterocycles, which have significant
      importance in current drug discovery. In this paper, we also report limitation of
      these method and unsuccessful attempt to prepare an 8-membered benzodiazocine
      cycle. 

PMID- 23163898
TI  - No evidence of drug-induced pancreatitis in rats treated with exenatide for 13
      weeks.
AB  - AIMS: The potential association of glucagon-like peptide receptor agonists (GLP
      1RAs) with the development of pancreatitis or pancreatic malignancies in patients
      with diabetes has been suggested. This study evaluated the long-term effects of
      the GLP-1RA exenatide on pancreatic exocrine structure and function in the Zucker
      diabetic fatty (ZDF) rat model of type 2 diabetes. METHODS: Rats received
      subcutaneous twice-daily injections of 0 (control), 6, 40 and 250 ug/kg/day
      exenatide for 3 months. Clinical signs, body and pancreas weight, food
      consumption, HbA1c, fasting serum amylase, lipase, glucose and insulin
      concentrations were evaluated during treatment and after a 28-day off-drug period
      to assess the reversibility of any observed effects. Morphometric analysis of
      pancreatic ductal cell proliferation and apoptosis were performed. RESULTS:
      Plasma exenatide concentrations were several-fold higher than therapeutic levels
      observed in humans. No exenatide-related effects were observed on clinical signs,
      lipase concentration, pancreatic weight, pancreatic histology, ductal cell
      proliferation or apoptosis. Exenatide improved animal survival, physical
      condition, glucose concentrations and HbA1c, decreased food intake, and increased
      serum insulin concentration. Total amylase concentrations, although within normal
      ranges, were slightly higher in exenatide-treated rats; following the off-drug
      period, total amylase concentrations were comparable in treated and untreated
      rats. Exenatide-related minimal-to-moderate islet hypertrophy was observed at
      doses >=6 ug/kg/day, with dose-related increases in incidence and degree. These
      changes were still present after the off-drug period. CONCLUSIONS: Chronic
      administration of exenatide in ZDF rats resulted in the expected metabolic
      benefits and improved animal survival, with no adverse effects noted on
      pancreatic exocrine structure and function.

PMID- 23163900
TI  - Synthesis and properties of a covalently linked angular perylene imide dimer.
AB  - Utilizing the unexplored chemistry of a monocarbon analog to perylene bisimide, a
      covalently linked angular perylene dimer was synthesized. On the basis of
      measured optical properties and molecular modeling, the spectral changes relative
      to a monomeric reference perylene can be explained by an angle-dependent oblique
      exciton coupling model. With a roughly trigonal interchromophore arrangement, the
      dimer building block is promising for larger, cyclic assemblies to mimic
      naturally occurring light harvesting complexes.

PMID- 23163901
TI  - The response threshold of Salmonella PilZ domain proteins is determined by their
      binding affinities for c-di-GMP.
AB  - c-di-GMP is a bacterial second messenger that is enzymatically synthesized and
      degraded in response to environmental signals. Cellular processes are affected
      when c-di-GMP binds to receptors which include proteins that contain the PilZ
      domain. Although each c-di-GMP synthesis or degradation enzyme metabolizes the
      same molecule, many of these enzymes can be linked to specific downstream
      processes. Here we present evidence that c-di-GMP signalling specificity is
      achieved through differences in affinities of receptor macromolecules. We show
      that the PilZ domain proteins of Salmonella Typhimurium, YcgR and BcsA,
      demonstrate a 43-fold difference in their affinity for c-di-GMP. Modulation of
      the affinities of these proteins altered their activities in a predictable manner
      in vivo. Inactivation of yhjH, which encodes a predicted c-di-GMP degrading
      enzyme, increased the fraction of the cellular population that demonstrated c-di
      GMP levels high enough to bind to the higher-affinity YcgR protein and inhibit
      motility, but not high enough to bind to the lower-affinity BcsA protein and
      stimulate cellulose production. Finally, PilZ domain proteins of Pseudomonas
      aeruginosa demonstrated a 145-fold difference in binding affinities, suggesting
      that regulation by binding affinity may be a conserved mechanism that allows
      organisms with many c-di-GMP binding macromolecules to rapidly integrate multiple
      environmental signals into one output.

PMID- 23163903
TI  - Chemical optimization of protein extraction from sweet potato (Ipomoea batatas)
      peel.
AB  - Proteins isolated from sweet potatoes (Ipomoea batatas) have been shown to
      possess antidiabetic, antioxidant, and antiproliferative properties. The
      objective of this study was to chemically optimize a process for extracting
      proteins from sweet potato peel. The extraction procedure involved mixing peel
      with saline solvent to dissolve proteins and then precipitating with CaCl(2).
      Quadratic and segmented models were used to determine the optimum NaCl
      concentration and peel to solvent ratio to maximize protein solubility while
      minimizing solvent usage. A segmented model was also used to optimize the
      concentration of CaCl(2) used for precipitation. The highest yield was obtained
      by mixing blanched peelings with 59.7 mL of 0.025 mM NaCl per g peel and then
      precipitating with 6.8 mM CaCl(2). The results of this study show that
      potentially valuable proteins can be extracted from peel generated during
      processing of sweet potatoes and industrial costs can be minimized by using these
      optimum conditions. PRACTICAL APPLICATION: Potentially valuable proteins can be
      extracted from sweet potato peel, a waste product of sweet potato processing.

PMID- 23163902
TI  - In vitro auxin treatment promotes cell division and delays endoreduplication in
      developing seeds of the model legume species Medicago truncatula.
AB  - The role of auxins in the morphogenesis of immature seeds of Medicago truncatula
      was studied, focusing on the transition from the embryo cell division phase to
      seed maturation. We analyzed seed development in vitro, by flow cytometry, and
      through the determination of the kinetics of seed fresh weight and size. Thus,
      seeds were harvested at 8, 10 and 12 days after pollination and cultured in vitro
      on a medium either without auxin or supplemented with indole-3-butyric acid (IBA)
      or naphthalene acetic acid (NAA) at 1 mg l(-1). All parameters studied were
      determined every 2 days from the start of in vitro culture. The results showed
      that both auxins increased the weight and size of seeds with NAA having a
      stronger effect than IBA. We further demonstrated that the auxin treatments
      modulate the transition between mitotic cycles and endocycles in M. truncatula
      developing seed by favoring sustained cell divisions while simultaneously
      prolonging endoreduplication, which is known to be the cytogenetical imprint of
      the transition from the cell division phase to the storage protein accumulation
      phase during seed development.

PMID- 23163904
TI  - Chocolate swelling during storage caused by fat or moisture migration.
AB  - Quantification of swelling in dark chocolate subjected to fat or moisture
      migration was conducted using a new method based on confocal chromatic
      displacement sensor. The nondestructive method allowed for the height profile of
      dark chocolate samples to be scanned with a sensitivity of +/- 2.8 MUm. By
      performing multiple scans on each sample prior to and after being subjected to
      fat or moisture migration, the induced swelling could be quantified. Applying the
      new method on confectionery systems revealed that fat and moisture migration
      generate different swelling behavior/kinetics in dark chocolate during storage.
      Moisture migration resulted in a rapid swelling once a water activity of 0.8 was
      reached in the chocolate, probably by interaction and absorption of moisture by
      the particulate solids. Fat migration also affected the swelling behavior in
      chocolate, possibly by inducing phase transitions in the continuous cocoa butter
      phase. Migrating fat also proved to induce a more pronounced swelling than the
      same amount of absorbed moisture which further consolidated that the observed
      swelling caused by fat or moisture migration is a result of significant different
      mechanisms.

PMID- 23163907
TI  - Inhibition of Clostridium perfringens spore germination and outgrowth by lemon
      juice and vinegar product in reduced NaCl roast beef.
AB  - Inhibition of Clostridium perfringens spore germination and outgrowth in reduced
      sodium roast beef by a blend of buffered lemon juice concentrate and vinegar
      (MoStatin LV1) during abusive exponential cooling was evaluated. Roast beef
      containing salt (NaCl; 1%, 1.5%, or 2%, w/w), blend of sodium pyro- and poly
      phosphates (0.3%), and MoStatin LV1 (0%, 2%, or 2.5%) was inoculated with a 3
      strain C. perfringens spore cocktail to achieve final spore population of 2.5 to
      3.0 log CFU/g. The inoculated products were heat treated and cooled exponentially
      from 54.4 to 4.4  degrees C within 6.5, 9, 12, 15, 18, or 21 h. Cooling of roast
      beef (2.0% NaCl) within 6.5 and 9 h resulted in <1.0 log CFU/g increase in C.
      perfringens spore germination and outgrowth, whereas reducing the salt
      concentration to 1.5% and 1.0% resulted in >1.0 log CFU/g increase for cooling
      times longer than 9 h (1.1 and 2.2 log CFU/g, respectively). Incorporation of
      MoStatin LV1 into the roast beef formulation minimized the C. perfringens spore
      germination and outgrowth to <1.0 log CFU/g, regardless of the salt concentration
      and the cooling time. PRACTICAL APPLICATION: Cooked, ready-to-eat meat products
      should be cooled rapidly to reduce the risk of Clostridium perfringens spore
      germination and outgrowth. Meat processors are reducing the sodium chloride
      content of the processed meats as a consequence of the dietary recommendations.
      Sodium chloride reduces the risk of C. perfringens spore germination and
      outgrowth in meat products. Antimicrobials that contribute minimally to the
      sodium content of the product should be incorporated into processed meats to
      assure food safety. Buffered lemon juice and vinegar can be incorporated into
      meat product formulations to reduce the risk of C. perfringens spore germination
      and outgrowth during abusive cooling.

PMID- 23163908
TI  - Discrimination of volatiles of refined and whole wheat bread containing red and
      white wheat bran using an electronic nose.
AB  - The principal objective of this study was to evaluate the capability of
      electronic (E) nose technology to discriminate refined and whole wheat bread made
      with white or red wheat bran according to their headspace volatiles. Whole wheat
      flour was formulated with a common refined flour from hard red spring wheat,
      blended at the 15% replacement level with bran milled from representative samples
      of one hard red and 2 hard white wheats. A commercial formula was used for
      breadmaking. Results varied according to the nature of the sample, that is,
      crust, crumb, or whole slices. Bread crust and crumb were completely
      discriminated. Crumb of whole wheat bread made with red bran was distinct from
      other bread types. When misclassified, whole wheat bread crumb with white bran
      was almost invariably identified as refined flour bread crumb. Using crust as the
      basis for comparisons, the largest difference in volatiles was between refined
      flour bread and whole wheat bread as a group. When refined flour bread crust was
      misclassified, samples tended to be confused with whole white wheat crust.
      Samples prepared from whole bread slices were poorly discriminated in general. E
      nose results indicated that whole wheat bread formulated with white bran was more
      similar in volatile makeup to refined flour bread compared to whole wheat bread
      made with red bran. The E-nose appears to be very capable to accommodate
      differentiation of bread volatiles whose composition varies due to differences in
      flour or bran type. PRACTICAL APPLICATION: Consumer preference of bread made
      using refined flour in contrast to whole wheat flour is partly due to the
      different aroma of whole wheat bread. This study used an electronic nose to
      analyze bread volatiles, and showed that whole wheat bread incorporating white
      bran was different from counterpart bread made using red bran, and was closer in
      volatile makeup to "white" bread made without bran. Commercial millers and bakers
      can take advantage of these results to formulate whole wheat flour with brans of
      preferred type in order to foster increased consumption of whole wheat products
      which confer many favorable health benefits.

PMID- 23163910
TI  - Long-term safety of linagliptin monotherapy in Japanese patients with type 2
      diabetes.
AB  - AIMS: In a phase III study conducted among Japanese patients with type 2 diabetes
      mellitus (T2DM), linagliptin 5 and 10 mg showed clinically meaningful
      improvements in glycaemic parameters after 12 and 26 weeks compared with placebo
      and voglibose, respectively. This extension study assessed long-term tolerability
      of linagliptin over 52 weeks. METHODS: Japanese patients with T2DM who completed
      either phase of a 12-week/26-week study comparing linagliptin monotherapy with
      placebo or voglibose were eligible to enrol. In the extension study, the
      comparator groups switched to linagliptin 5 or 10 mg, while the linagliptin
      groups maintained dosage. RESULTS: In all, 540 patients received at least one
      dose of linagliptin 5 or 10 mg and 494 completed the extension. Long-term
      treatment with linagliptin was well tolerated; adverse events (AEs) of special
      interest and serious AEs occurred in small percentages of patients. Drug-related
      AEs occurred in 10.2 and 10.6% of patients in the linagliptin 5- and 10-mg
      groups, respectively, and discontinuations due to drug-related AEs occurred in
      1.1 and 0.7%, respectively. Only one (0.4%) patient in each dose group
      experienced investigator-defined hypoglycaemia during the treatment period (both
      events were non-severe). Body weight was not clinically altered in either group.
      The glycated haemoglobin A1c profiles over time were similar with linagliptin 5
      and 10 mg. CONCLUSIONS: These findings provide evidence for the safety and
      tolerability of oral linagliptin at either 5 or 10 mg for up to 52 weeks for the
      treatment of Japanese patients with T2DM, without clinically relevant increase in
      the risk of hypoglycaemia or weight gain.

PMID- 23163911
TI  - A possible first use of the word astrobiology?
AB  - The word astrobiology was possibly first used in 1935, in an article published in
      a French popular science magazine. The author was Ary J. Sternfeld (1905-1980), a
      pioneer of astronautics who wrote numerous scientific books and papers. The
      article is remarkable because his portrayal of the concept is very similar to the
      way it is used today. Here I review the 1935 article and provide a brief history
      of Sternfeld's life, which was heavily influenced by the tragic events of 20(th)
      century history.

PMID- 23163912
TI  - Secular trends in weight, height and BMI in young Swedes: the 'Grow up
      Gothenburg' studies.
AB  - AIM: This study aims to document secular differences in anthropometry (level and
      variability of weight, height, BMI) in two cohorts born around 1990 and 1974 and
      examined as young adults. METHODS: Descriptive results are presented for the
      complete cohorts. The final analysis age-matched the cohorts (mean, 18.8 years)
      and employed CDC z-scores to compare means and distributions of weight, height
      and BMI. RESULTS: Z-scores for weight, height and BMI were higher in later-born
      (1990) boys, while in girls weight and height increased over this period without
      resulting in increased BMI. At the same time, in boys the BMI variances
      increased, confirming a simultaneous emergence of more overweight and more
      underweight. In girls, the BMI variance did not increase significantly.
      Sensitivity analyses, excluding subjects not born in Sweden, confirmed increasing
      BMI trends in boys. CONCLUSION: This study documents that gender differences in
      the recent childhood obesity epidemic can also be observed in young Swedes as
      they enter adulthood. Comparing two cohorts of high school students born around
      1974 or 1990, less favourable trends in weight status were seen in boys than in
      girls. Finally, secular increases in height, already observed earlier in the 20th
      century, continued in these more contemporary cohorts.

PMID- 23163913
TI  - Iodine-123 metaiodobenzylguanidine scintigraphy and iodine-123 ioflupane single
      photon emission computed tomography in Lewy body diseases: complementary or
      alternative techniques?
AB  - PURPOSE: To compare myocardial sympathetic imaging using (123)I
      Metaiodobenzylguanidine (MIBG) scintigraphy and striatal dopaminergic imaging
      using (123)I-Ioflupane (FP-CIT) single photon emission computed tomography
      (SPECT) in patients with suspected Lewy body diseases (LBD). METHODS: Ninety-nine
      patients who performed both methods within 2 months for differential diagnosis
      between Parkinson's disease (PD) and other parkinsonism (n = 68) or between
      dementia with Lewy bodies (DLB) and other dementia (n = 31) were enrolled.
      Sensitivity, specificity, accuracy, positive and negative predictive values of
      both methods were calculated. RESULTS: For (123) I-MIBG scintigraphy, the overall
      sensitivity, specificity, accuracy, positive and negative predictive values in
      LBD were 83%, 79%, 82%, 86%, and 76%, respectively. For (123)I-FP-CIT SPECT, the
      overall sensitivity, specificity, accuracy, positive and negative predictive
      values in LBD were 93%, 41%, 73%, 71%, and 80%, respectively. There was a
      statistically significant difference between these two methods in patients
      without LBD, but not in patients with LBD. CONCLUSIONS: LBD usually present both
      myocardial sympathetic and striatal dopaminergic impairments. (123)I-FP-CIT SPECT
      presents high sensitivity in the diagnosis of LBD; (123)I-MIBG scintigraphy may
      have a complementary role in differential diagnosis between PD and other
      parkinsonism. These scintigraphic methods showed similar diagnostic accuracy in
      differential diagnosis between DLB and other dementia.

PMID- 23163914
TI  - Transcriptional control of lipid metabolism by the MarR-like regulator FamR and
      the global regulator GlxR in the lipophilic axilla isolate Corynebacterium
      jeikeium K411.
AB  - Corynebacterial fatty acid metabolism has been associated with human body odour,
      and is therefore discussed as a potential target for the development of new
      deodorant additives. For this reason, the transcription levels of fad genes
      associated with lipid metabolism in the axilla isolate Corynebacterium jeikeium
      were analysed during growth on different lipid sources. The transcription of
      several fad genes was induced two- to ninefold in the presence of Tween 60,
      including the acyl-CoA dehydrogenase gene fadE6. DNA affinity chromatography
      identified the MarR-like protein FamR as candidate regulator of fadE6. DNA band
      shift assays and in vivo reporter gene fusions confirmed the direct interaction
      of FamR with the mapped fadE6 promoter region. Moreover, DNA affinity
      chromatography and DNA band shift assays detected the binding of GlxR to the
      promoter regions of fadE6 and famR, revealing a hierarchical control of fadE6
      transcription by a feed-forward loop. Binding of GlxR and FamR to additional fad
      gene regions was demonstrated in vitro by DNA band shift assays, resulting in the
      co-regulation of fadA, fadD, fadE and fadH genes. These results shed first light
      on the hierarchical transcriptional control of lipid metabolism in C. jeikeium, a
      pathway associated with the development of human axillary odour.

PMID- 23163915
TI  - Radiographic evaluation of different techniques for ridge preservation after
      tooth extraction: a randomized controlled clinical trial.
AB  - OBJECTIVE: To evaluate the radiographic changes of the alveolar ridge following
      application of different ridge preservation techniques 6 months after tooth
      extraction. MATERIALS AND METHODS: Four treatment modalities were randomly
      assigned in 40 patients: beta-tricalcium-phosphate-particles with polylactid
      coating (beta-TCP), demineralized bovine bone mineral with 10% collagen covered
      with a collagen matrix (DBBM-C/CM), DBBM-C covered with an autogenous soft-tissue
      graft (DBBM-C/PG) and spontaneous healing (control). Cone-beam computed
      tomography scans were performed after treatment and 6 months later. RESULTS:
      After 6 months, the vertical changes ranged between -0.6 mm (-10.2%) for control
      and a gain of 0.3 mm (5.6%) for DBBM-C/PG on the lingual side, and between -2.0
      mm (-20.9%) for beta-TCP and a gain of 1.2 mm (8.1%) for DBBM-C/PG on the buccal
      side. The most accentuated ridge width changes were recorded 1 mm below the
      crest: -3.3 mm (-43.3%, C), -6.1 mm (-77.5%, beta-TCP), -1.2 mm (-17.4%, DBBM
      C/CM) and -1.4 mm (-18.1%, DBBM-C/PG). At all three levels, DBBM-C with either CM
      or PG was not significantly differing (p > 0.05), while most other differences
      between the groups reached statistical significance (p < 0.05). CONCLUSIONS:
      Application of DBBM-C, covered with CM or PG, resulted in less vertical and
      horizontal changes of the alveolar ridge as compared with controls 6 months after
      extraction.

PMID- 23163916
TI  - Effects of antimicrobials fed as dietary growth promoters on faecal shedding of
      Campylobacter, Salmonella and shiga-toxin producing Escherichia coli in swine.
AB  - AIMS: To determine whether antimicrobials commonly used in swine diets affect
      zoonotic pathogen shedding in faeces. METHODS AND RESULTS: Barrows (n = 160) were
      sorted into two treatments at 10 weeks of age (week 0 of the study), and fed
      growing, grow finishing and finishing diets in 4-week feeding periods. For each
      feeding phase, diets were prepared without (A-) and with (A+) dietary
      antimicrobials (chlortetracycline, 0-8 week; bacitracin, 9-12 week) typical of
      the United States. At week 0, 4, 8, 9, 10 and 12 of the study, faecal swabs or
      grabs were collected for analyses. Campylobacter spp. was absent at week 0, but
      prevalence increased over time with most isolates being identified as
      Campylobacter coli. When chlortetracycline was used in A+ diets (week 4 and 8),
      prevalence for Campylobacter spp., pathogenic Escherichia coli O26 and stx genes
      was lower in faeces. On week 12 after the shift to bacitracin, Campylobacter spp.
      and stx genes were higher in faeces from piglets fed A+ diet. Pathogenic E. coli
      serogroups O103 and O145 were isolated throughout the study and their prevalence
      did not differ due to diet. Pathogenic E. coli serogroups O111 and O121 were
      never found in the piglets, and Salmonella spp. prevalence was low. CONCLUSIONS:
      In production swine, growing diets with chlortetracycline may have reduced
      pathogen shedding compared with the A-growing diets, whereas finishing diets with
      bacitracin may have increased pathogen shedding compared with the A-finishing
      diet. SIGNIFICANCE AND IMPACT OF THE STUDY: Inclusion of antimicrobials in the
      diet can affect zoonotic pathogen shedding in faeces of swine.

PMID- 23163917
TI  - Adaptive response to starvation in the fish pathogen Flavobacterium columnare:
      cell viability and ultrastructural changes.
AB  - BACKGROUND: The ecology of columnaris disease, caused by Flavobacterium
      columnare, is poorly understood despite the economic losses that this disease
      inflicts on aquaculture farms worldwide. Currently, the natural reservoir for
      this pathogen is unknown but limited data have shown its ability to survive in
      water for extended periods of time. The objective of this study was to describe
      the ultrastructural changes that F. columnare cells undergo under starvation
      conditions. Four genetically distinct strains of this pathogen were monitored for
      14 days in media without nutrients. Culturability and cell viability was assessed
      throughout the study. In addition, cell morphology and ultrastructure was
      analyzed using light microscopy, scanning electron microscopy, and transmission
      electron microscopy. Revival of starved cells under different nutrient conditions
      and the virulence potential of the starved cells were also investigated. RESULTS:
      Starvation induced unique and consistent morphological changes in all strains
      studied. Cells maintained their length and did not transition into a shortened,
      coccus shape as observed in many other Gram negative bacteria. Flavobacterium
      columnare cells modified their shape by morphing into coiled forms that comprised
      more than 80% of all the cells after 2 weeks of starvation. Coiled cells remained
      culturable as determined by using a dilution to extinction strategy.
      Statistically significant differences in cell viability were found between
      strains although all were able to survive in absence of nutrients for at least 14
      days. In later stages of starvation, an extracellular matrix was observed
      covering the coiled cells. A difference in growth curves between fresh and
      starved cultures was evident when cultures were 3-months old but not when
      cultures were starved for only 1 month. Revival of starved cultures under
      different nutrients revealed that cells return back to their original elongated
      rod shape upon encountering nutrients. Challenge experiments shown that starved
      cells were avirulent for a fish host model. CONCLUSIONS: Specific morphological
      and ultrastructural changes allowed F. columnare cells to remain viable under
      adverse conditions. Those changes were reversed by the addition of nutrients.
      This bacterium can survive in water without nutrients for extended periods of
      time although long-term starvation appears to decrease cell fitness and resulted
      in loss of virulence.

PMID- 23163918
TI  - Arenium acid catalyzed deuteration of aromatic hydrocarbons.
AB  - The arenium acid [mesitylene-H](+) has been shown to be an extraordinarily active
      H/D exchange catalyst for the perdeuteration of polycyclic aromatic hydrocarbons.
      The reactions take place under ambient conditions in C6D6 as an inexpensive
      deuterium source. High isolated yields and excellent degrees of deuterium
      incorporation were achieved using the substrates p-terphenyl, fluoranthene,
      pyrene, triphenylene, and corannulene.

PMID- 23163919
TI  - High-resolution computational imaging of leaf hair patterning using polarized
      light microscopy.
AB  - The leaf hairs (trichomes) on the aerial surface of many plant species play
      important roles in phytochemical production and herbivore protection, and have
      significant applications in the chemical and agricultural industries. Trichome
      formation in the model plant Arabidopsis thaliana also presents a tractable
      experimental system to study cell differentiation and pattern formation in plants
      and animals. Studies of this developmental process suggest that trichome
      positioning may be the result of a self-forming pattern, emerging from a lateral
      inhibition mechanism determined by a network of regulatory factors. Critical to
      the continued success of these studies is the ability to quantitatively
      characterize trichome pattern phenotypes in response to mutations in the genes
      that regulate this process. Advanced protocols for the observation of changes in
      trichome patterns can be expensive and/or time consuming, and lack user-friendly
      analysis tools. In order to address some of these challenges, we describe here a
      strategy based on polarized light microscopy for the quick and accurate
      measurement of trichome positions, and provide an online tool designed for the
      quantitative analyses of trichome number, density and patterning.

PMID- 23163920
TI  - Association of asthma education with asthma control evaluated by asthma control
      test, FEV1, and fractional exhaled nitric oxide.
AB  - BACKGROUND: Asthma education is an important adjunct for asthma control although
      the way asthma education affects asthma outcomes is poorly understood. The asthma
      control test (ACT), forced expiratory volume in 1 s (FEV(1)), and fractional
      exhaled nitric oxide (FeNO) have all been used as markers of asthma control.
      However, the use of FeNO as a surrogate marker remains controversial. OBJECTIVES:
      (i) To examine whether asthma education is associated with asthma control; (ii)
      to compare absolute levels and changes of ACT, FEV(1), and FeNO over a year; and
      (iii) to evaluate whether FeNO can be used as an additional marker of asthma
      control. METHODS: Fifty asthmatics with poor adherence (12 mild, 21 moderate, and
      17 severe) received asthma education at study entry. Medications were unchanged
      for the first 3 months, and ACT, FEV(1), and FeNO measurements were recorded at
      entry, 3, 6, and 12 months. Asthma control was assessed at each visit and
      patients were categorized as either "stable" or "unstable" asthmatics according
      to the global initiative for asthma (GINA) guidelines. RESULTS: A significant
      decrease in FeNO and increase in ACT score were noted in the stable asthmatic
      group at 3 months (p < .001), and this persisted over 12 months. Significant
      correlations were seen between changes (Delta) in FeNO, ACT, and FEV(1) over
      time. However, significant correlations between the absolute levels were not
      maintained over 12 months. A decrease of >=18.6% in FeNO and a >=3-point increase
      in ACT score (sensitivity: 80% and 73.3% and specificity: 83.3% and 87.5%,
      respectively) were associated with stable asthma control although the absolute
      levels were not. CONCLUSIONS: Asthma education may be useful to achieve stable
      control. In addition, changes rather than absolute levels of FeNO and ACT may be
      better markers of asthma control.

PMID- 23163921
TI  - Depsides and triterpenes in Pseudocyphellaria coriifolia (lichens) and biological
      activity against Trypanosoma cruzi.
AB  - The lichen Pseudocyphellaria coriifolia is a species endemic to southern South
      America. From the lichen thallus, methyl evernate, tenuiorin and three hopane
      triterpenoids were isolated and identified as the main lichen constituents. Their
      trypanocidal effects were screened against epimastigotes of Trypanosoma cruzi.
      The results of the biological test showed that some hopane terpenoids exhibit
      antiparasitic properties.

PMID- 23163922
TI  - Growth of polythiophene/perylene tetracarboxydiimide donor/acceptor shish-kebab
      nanostructures by coupled crystal modification.
AB  - Self-assembled crystalline organic nanostructures containing electron donor and
      acceptor materials hold promise as building blocks for photovoltaic devices. We
      show that coupled crystallization of poly(3-hexyl thiophene) (P3HT) and perylene
      tetracarboxydiimide (PDI) induced by solvent evaporation, wherein both components
      modify crystallization of the other, gives rise to donor/acceptor "shish-kebabs"
      with tunable nanostructures. P3HT kinetically stabilizes supersaturated solutions
      of PDI and modifies the growth of PDI crystals, leading to formation of extended
      PDI shish nanowires that in turn serve as heterogeneous nucleation sites for
      fibrillar P3HT kebabs during solvent casting. The dimensions of these
      nanostructures can be tailored through variations in donor/acceptor ratio or
      solvent quality, and the method is shown to be general to several other poly(3
      alkyl thiophenes) and perylene derivatives, thus providing a simple and robust
      route to form highly crystalline nanophase separated organic donor/acceptor
      assemblies.

PMID- 23163923
TI  - Open tibial fractures grade IIIC treated successfully with external fixation,
      negative-pressure wound therapy and recombinant human bone morphogenetic protein
      7.
AB  - The aim of the therapy in open tibial fractures grade III was to cover the bone
      with soft tissue and achieve healed fracture without persistent infection. Open
      tibial fractures grade IIIC with massive soft tissue damage require combined
      orthopaedic, vascular and plastic-reconstructive procedures. Negative-pressure
      wound therapy (NPWT), used in two consecutive cases with open fracture grade IIIC
      of the tibia diaphysis, healed extensive soft tissue defect with exposure of the
      bone. NPWT eventually allowed for wound closure by split skin graft within 21-25
      days. Ilizarov external fixator combined with application of recombinant human
      bone morphogenetic protein-7 at the site of delayed union enhanced definitive
      bone healing within 16-18 months. 

PMID- 23163924
TI  - A serological method for detection of Nosema ceranae.
AB  - AIMS: We developed a new method for detection of the intracellular parasite,
      Nosema ceranae, one of the most economically devastating pathogens of the
      honeybee. METHODS AND RESULTS: The SWP-32 antibody was used for the development
      of an enzyme-linked immunosorbent assay (ELISA). We also compared the efficiency
      of this ELISA to microscopy and quantitative real-time (qRT) PCR, the methods
      currently in use. CONCLUSIONS: ELISA is comparable in sensitivity with the qRT
      PCR, less expensive and faster. When this method is commercialized and made
      available to bee-keepers, it will allow them to make informed decisions for the
      application of in-hive chemicals. Hence, bee-keepers may be able to determine
      when treatments for control of N. ceranae are unnecessary and reduce the cost,
      time and possible side effects of these treatments. SIGNIFICANCE AND IMPACT OF
      THE STUDY: This assay provides the first serological method for detection of N.
      ceranae in bee colonies, which is as sensitive as DNA amplification. It can be
      easily adopted for both laboratory and field applications.

PMID- 23163925
TI  - Oleoylethanolamide dose-dependently attenuates cocaine-induced behaviours through
      a PPARalpha receptor-independent mechanism.
AB  - Oleoylethanolamide (OEA) is an acylethanolamide that acts as an agonist of
      nuclear peroxisome proliferator-activated receptor alpha (PPARalpha) to exert
      their biological functions, which include the regulation of appetite and
      metabolism. Increasing evidence also suggests that OEA may participate in the
      control of reward-related behaviours. However, direct experimental evidence for
      the role of the OEA-PPARalpha receptor interaction in drug-mediated behaviours,
      such as cocaine-induced behavioural phenotypes, is lacking. The present study
      explored the role of OEA and its receptor PPARalpha on the psychomotor and
      rewarding responsiveness to cocaine using behavioural tests indicative of core
      components of addiction. We found that acute administration of OEA (1, 5 or 20
      mg/kg, i.p.) reduced spontaneous locomotor activity and attenuated psychomotor
      activation induced by cocaine (20 mg/kg) in C57Bl/6 mice. However, PPARalpha
      receptor knockout mice showed normal sensitization, although OEA was capable of
      reducing behavioural sensitization with fewer efficacies. Furthermore,
      conditioned place preference and reinstatement to cocaine were intact in these
      mice. Our results indicate that PPARalpha receptor does not play a critical, if
      any, role in mediating short- and long-term psychomotor and rewarding
      responsiveness to cocaine. However, further research is needed for the
      identification of the targets of OEA for its inhibitory action on cocaine
      mediated responses.

PMID- 23163926
TI  - Who should treat rectal cancer and how?

PMID- 23163927
TI  - Commentary on Lewis R et al.

PMID- 23163928
TI  - Results from randomized studies may differ from those obtained from large
      prospective multi-centre databases.

PMID- 23163932
TI  - Secretory production of an FAD cofactor-containing cytosolic enzyme (sorbitol
      xylitol oxidase from Streptomyces coelicolor) using the twin-arginine
      translocation (Tat) pathway of Corynebacterium glutamicum.
AB  - Carbohydrate oxidases are biotechnologically interesting enzymes that require a
      tightly or covalently bound cofactor for activity. Using the industrial workhorse
      Corynebacterium glutamicum as the expression host, successful secretion of a
      normally cytosolic FAD cofactor-containing sorbitol-xylitol oxidase from
      Streptomyces coelicolor was achieved by using the twin-arginine translocation
      (Tat) protein export machinery for protein translocation across the cytoplasmic
      membrane. Our results demonstrate for the first time that, also for cofactor
      containing proteins, a secretory production strategy is a feasible and promising
      alternative to conventional intracellular expression strategies.

PMID- 23163933
TI  - An exploratory study investigating children's perceptions of dental behavioural
      management techniques.
AB  - BACKGROUND: Behaviour management techniques (BMTs) are utilised by dentists to
      aid children's dental anxiety (DA). Children's perceptions of these have been
      underexplored, and their feedback could help inform paediatric dentistry. AIM: To
      explore children's acceptability and perceptions of dental communication and BMTs
      and to compare these by age, gender, and DA. DESIGN: A total of sixty-two 9- to
      11-year-old school children participated in the study. Children's acceptability
      of BMTs was quantified using a newly developed Likert scale, alongside
      exploration of children's experiences and perceptions through interviews. anova
      and t-tests explored BMT acceptability ratings by age, gender, and DA. Thematic
      analysis was used to analyse interviews. FINDINGS: Statistical analyses showed no
      effect of age, gender, or DA upon BMT acceptability. Children generally perceived
      the BMTs as acceptable or neutral; stop signals were the most acceptable, and
      voice control the least acceptable BMT. Beneficial experiences of distraction and
      positive reinforcement were common. Children described the positive nature of
      their dentist's communication and BMT utilisation. CONCLUSION: Dental anxiety did
      not affect children's perceptions of BMTs. Children were generally positive about
      dentist's communication and established BMTs. Children's coping styles may impact
      perceptions and effectiveness of BMTs and should be explored in future
      investigations.

PMID- 23163934
TI  - Effect of Bizhongxiao decoction and its dismantled formulae on IL-1 and TNF
      levels in collagen-induced arthritis in rat synovial joints.
AB  - BACKGROUND: Rheumatoid arthritis (RA), a chronic autoimmune disease, affects
      sufferers in many different ways. Treatment of this chronic condition is
      particularly challenging. Traditional Chinese Medicine (TCM) provides
      alternatives. Bizhongxiao decoction (BZX) is a TCM complex, which has been used
      clinically for many years to treat RA. The purpose of this study is to compare
      the effects of BZX decoction and its dismantled formulae on IL-1 and TNF-1 levels
      in rats with RA, and to elucidate its mechanism of action. METHODS: Ninety
      healthy normal female SD rats were randomly divided into six groups: normal
      (control), model, BZX decoction, and the three dismantled formulae (I: heat
      clearing and detoxication, II: dissipating dampness, and III: blood circulation
      promotion). Apart from the normal (control) group, the rats in each group were
      injected subcutaneously with bovine type II collagen and complete Freund adjuvant
      to establish a collagen-induced arthritis model, so that inhibition of foot
      swelling in the rats by BZX decoction and its dismantled formulae could be
      observed. Immunohistochemistry was used to assess the levels of the inflammatory
      cytokines IL-1 and TNF in synovial joints at various time points. RESULTS: Twenty
      one days after the model was established, the levels of TNF and IL-1 were
      significantly higher in the model group, BZX decoction group and dismantled
      formula groups I, II and III than in the normal controls (P < 0.05). The levels
      of these cytokines were significantly higher in the model group than the BZX
      decoction or the three dismantled formula groups (P <0.01). At longer times, the
      TNF and IL-1 levels in model group rose gradually; those in the BZX decoction and
      dismantled formula groups were gradually reduced. The cytokine levels in the BZX
      decoction group were lower than in the three dismantled formula groups and
      continued to decline. CONCLUSIONS: BZX decoction and the three dismantled
      formulae examined down-regulated the inflammatory factors IL-1 and TNF in
      collagen-induced arthritis rat models, but BZX exerted the strongest effect.

PMID- 23163935
TI  - Novel skeleton transformation reaction of alpha-pyrone derivatives to
      spirobicyclo[3.1.0]hexane derivatives using dimethylsulfoxonium methylide.
AB  - By applying a skeleton transformation reaction using dimethylsulfoxonium
      methylide, a novel reaction was identified by which 5,6,7,8-tetrahydrocoumarin
      with the electron-withdrawing group at C3 was led to the
      spirobicyclo[3.1.0]hexane-cyclohexane derivative. Moreover, by establishing the
      scope of this reaction, it was confirmed that it is possible to apply this
      reaction to not only ring-fused alpha-pyrone derivatives but also alkyl-chain
      substituted alpha-pyrone derivatives in moderate to good yields.

PMID- 23163936
TI  - Optimization of hull-less pumpkin seed roasting conditions using response surface
      methodology.
AB  - Response surface methodology (RSM) was applied to optimize hull-less pumpkin seed
      roasting conditions before seed pressing to maximize the biochemical composition
      and antioxidant capacity of the virgin pumpkin oils obtained using a hydraulic
      press. Hull-less pumpkin seeds were roasted for various lengths of time (30 to 70
      min) at various roasting temperatures (90 to 130  degrees C), resulting in 9
      different oil samples, while the responses were phospholipids content, total
      phenols content, alpha- and gamma-tocopherols, and antioxidative activity [by 2,2
      diphenyl-1-picrylhydrazyl (DPPH) free-radical assay]. Mathematical models have
      shown that roasting conditions influenced all dependent variables at P < 0.05.
      The higher roasting temperatures had a significant effect (P < 0.05) on
      phospholipids, phenols, and alpha-tocopherols contents, while longer roasting
      time had a significant effect (P < 0.05) on gamma-tocopherol content and
      antioxidant capacity, among the samples prepared under different roasting
      conditions. The optimum conditions for roasting the hull-less pumpkin seeds were
      120  degrees C for duration of 49 min, which resulted in these oil
      concentrations: phospholipids 0.29%, total phenols 23.06 mg/kg, alpha-tocopherol
      5.74 mg/100 g, gamma-tocopherol 24.41 mg/100 g, and an antioxidative activity
      (EC(50)) of 27.18 mg oil/mg DPPH.

PMID- 23163937
TI  - Influence of various cooking methods on the concentrations of volatile N
      nitrosamines and biogenic amines in dry-cured sausages.
AB  - N-nitrosamines, biogenic amines, and residual nitrites are harmful substances and
      are often present in cured meats. The effects of different cooking methods
      (boiling, pan-frying, deep-frying, and microwave) were investigated on their
      contents in dry-cured sausage. The various N-nitrosamines were isolated by a
      steam distillation method and analyzed by gas chromatography mass spectrometry
      (GC-MS). The biogenic amines were determined after extraction with perchloric
      acid as dansyl derivatives by high-performance liquid chromatography (HPLC)
      method. The results showed that initial dry-cured raw sausage contained 5.31
      MUg/kg of total N-nitrosamines. Cooking by deep-frying or pan-frying resulted in
      products having the highest (P < 0.05) contents, compared with boiling or
      microwave treatments, which were not different from the raw. Although frying
      increased the content of N-nitrosodimethylamine (NDMA), N-nitrosodiethylamine
      (NDEA), and N-nitrosopyrrolidine (NPYR), it decreased the contents of histamine
      and cadaverine. Boiling and microwave treatments decreased the total biogenic
      amines significantly (P < 0.05). Residual nitrite was significantly reduced by
      cooking treatments. The results suggest that boiling and microwave treatments
      were more suitable methods for cured meat.

PMID- 23163938
TI  - Glass transition study in model food systems prepared with mixtures of fructose,
      glucose, and sucrose.
AB  - The glass transition temperature of model food systems prepared with several
      glucose/fructose/sucrose mass fractions was studied using differential scanning
      calorimetry (DSC). A distance-based experimental design for mixtures of 3
      components was used to establish the proportion of sugars of the model systems.
      Thus, 32 compositions including individual sugars and sugar mixtures, both binary
      and ternary were prepared and analyzed. Thermograms showing the complete process
      of heating-cooling-reheating were used to determine the precise glass transition
      temperature during cooling (T(g)(c)) or reheating (T(g)(H) in amorphous sugars.
      The Scheffe cubic model was applied to experimental results to determine the
      influence of sugar composition on the glass transition temperature (P < 0.05).
      The final model proved to be appropriate (R(2) > 0.97, CV < 9%, model
      significance <0.0001) to predict the T(g) values of any dry mixture of amorphous
      fructose, glucose, and sucrose.

PMID- 23163939
TI  - Effect of molecular weight, acid, and plasticizer on the physicochemical and
      antibacterial properties of beta-chitosan based films.
AB  - Effects of chitosan molecular weight (1815 and 366 kDa), type of acid (1% acetic,
      formic, and propionic acid, or 0.5% lactic acid) and plasticizer (0, 25% glycerol
      or sorbital w/w chitosan) on the mechanical, water barrier, and antibacterial
      properties of beta-chitosan films were investigated. Tensile strength (TS) of
      high molecular weight (Hw) films was 53% higher than that of low molecular weight
      (Lw) ones, acetate, and propionate films had the highest TS (43 and 40 MPa) among
      tested acids, and plasticizer-reduced film TS 34%. Film elongation at break (EL)
      was higher in Hw films than in Lw ones, in which formate and acetate films were
      the highest (9% and 8%, respectively), and plasticizer increased the film EL
      128%. Molecular weight of chitosan did not influence water vapor permeability
      (WVP) of the films. Acetate and propionate films had lower WVP than other acid
      types of films, and plasticizer increased film WVP about 35%. No difference was
      found between glycerol and sorbitol films in terms of film mechanical and water
      barrier properties. Lw beta-chitosan films showed significant antibacterial
      activity against E. coli and L. innocua. This study demonstrated that beta
      chitosan films are compatible to alpha-chitosan films in physicochemical
      properties and antibacterial activity, yet with simple sample preparation.

PMID- 23163940
TI  - Effect of supercritical carbon dioxide pasteurization on natural microbiota,
      texture, and microstructure of fresh-cut coconut.
AB  - The objective of the present study was the evaluation of the effectiveness of
      supercritical carbon dioxide (SC-CO(2)) as a nonthermal technology for the
      pasteurization of fresh-cut coconut, as an example of ready-to-eat and minimally
      processed food. First, the inactivation kinetics of microbiota on coconut were
      determined using SC-CO(2) treatments (pressures at 8 and 12 MPa, temperatures
      from 24 to 45  degrees C, treatment times from 5 to 60 min). Second, the effects
      of SC-CO(2) on the hardness and microstructure of fresh-cut coconut processed at
      the optimal conditions for microbial reduction were investigated. SC-CO(2)
      treatment of 15 min at 45  degrees C and 12 MPa induced 4 log CFU/g reductions of
      mesophilic microorganisms, lactic acid bacteria, total coliforms, and yeasts and
      molds. The hardness of coconut was not affected by the treatment but the samples
      developed an irregular and disorderly microstructure. Results suggested the
      potential of SC-CO(2) in preserving fresh-cut fruits and ready-to-eat products.

PMID- 23163942
TI  - Processed tart cherry products--comparative phytochemical content, in vitro
      antioxidant capacity and in vitro anti-inflammatory activity.
AB  - Processing of fruits and vegetables affects their phytochemical and nutrient
      content. Tart cherries are commercially promoted to possess antioxidant and anti
      inflammatory activity. However, processing affects their phytochemical content
      and may affect their related health benefits. The current study compares the in
      vitro antioxidant capacity and anti-inflammatory cyclooxygenase activity of
      processed tart cherry (Prunus cerasus) products-cherry juice concentrate,
      individually quick-frozen cherries, canned cherries, and dried cherries. Cherry
      products were analyzed for total anthocyanin and proanthocyanidin content and
      profile. On a per serving basis, total anthocyanins were highest in frozen
      cherries and total proanthocyanidins were highest in juice concentrate. Total
      phenolics were highest in juice concentrate. Juice concentrate had the highest
      oxygen radical absorbance capacity (ORAC) and peroxynitrite radical averting
      capacity (NORAC). Dried cherries had the highest hydroxyl radical averting
      capacity (HORAC) and superoxide radical averting capacity (SORAC). Processed tart
      cherry products compared very favorably to the U.S. Dept. of Agriculture-reported
      ORAC of other fresh and processed fruits. Inhibition of in vitro inflammatory COX
      1 activity was greatest in juice concentrate. In summary, all processed tart
      cherry products possessed antioxidant and anti-inflammatory activity, but
      processing differentially affected phytochemical content and in vitro
      bioactivity. On a per serving basis, juice concentrate was superior to other tart
      cherry products.

PMID- 23163941
TI  - Fabrication of reduced fat products by controlled heteroaggregation of oppositely
      charged lipid droplets.
AB  - This study describes how the rheological properties of colloidal dispersions
      formed by heteroaggregation of oppositely charged protein-coated lipid droplets
      depend on total particle concentration. Mixed-particle emulsions were formed by
      mixing single-particle emulsions containing either beta-lactoglobulin-coated
      lipid droplets (zeta~-42 mV, d(43)~ 0.35 MUm) or lactoferrin (LF)-coated lipid
      droplets (zeta~+26 mV, d(43)~ 0.32 MUm). A series of single-particle and mixed
      particle emulsions with different total fat contents (5% to 40%) were prepared,
      and their mean particle size, apparent viscosity, and shear modulus were
      measured. Mixed-particle emulsions (40% LF: 60%beta-Lg) containing relatively
      high fat contents (>10%) had high viscosities and paste-like properties. These
      rheological characteristics were attributed to extensive particle aggregation and
      network formation due to electrostatic attraction between oppositely charged
      droplets. The viscosities of mixed-particle emulsions were much higher than those
      of single-particle emulsions with equivalent fat contents. Measurements of the
      color coordinates (L*, a*, b*) of mixed-particle emulsions with low fat contents
      showed that they had similar appearances as single-particle emulsions with high
      fat contents. This study has important implications for the creation of reduced
      fat foods with similar sensory qualities as higher fat foods.

PMID- 23163944
TI  - Microencapsulation of Bifidobacterium bifidum F-35 in whey protein-based
      microcapsules by transglutaminase-induced gelation.
AB  - Bifidobacterium bifidum F-35 was microencapsulated into whey protein
      microcapsules (WPMs) by a transglutaminase (TGase)-induced method after
      optimization of gelation conditions. The performance of these WPMs was compared
      with that produced by a spray drying method (WPMs-A). WPMs produced by the TGase
      induced gelation method (WPMs-B) had larger and denser structures in
      morphological examinations. Native gel and SDS-PAGE analyses showed that most of
      the polymerization observed in WPMs-B was due to stable covalent crosslinks
      catalyzed by TGase. The degradation properties of these WPMs were investigated in
      simulated gastric juice (SGJ) with or without pepsin. In the presence of pepsin,
      WPMs-A degraded more quickly than did WPMs-B. Finally, survival rates of the
      microencapsulated cells in both WPMs were significantly better than that of free
      cells and varied with the microencapsulation method. However, WPMs-B produced by
      TGase-induced gelation could provide better protection for microencapsulated
      cells in low pH conditions and during 1 mo of storage at 4  degrees C or at
      ambient temperature.

PMID- 23163945
TI  - Application of ozonated dry ice (ALIGALTM Blue Ice) for packaging and transport
      in the food industry.
AB  - Dry ice is used by meat and poultry processors for temperature reduction during
      processing and for temperature maintenance during transportation. ALIGALTM Blue
      Ice (ABI), which combines the antimicrobial effect of ozone (O(3)) along with the
      high cooling capacity of dry ice, was investigated for its effect on bacterial
      reduction in air, in liquid, and on food and glass surfaces. Through proprietary
      means, O(3) was introduced to produce dry ice pellets to a concentration of 20
      parts per million (ppm) by total weight. The ABI sublimation rate was similar to
      that of dry ice pellets under identical conditions, and ABI was able to hold the
      O(3) concentration throughout the normal shelf life of the product. Challenge
      studies were performed using different microorganisms, including E. coli,
      Campylobacter jejuni, Salmonella, and Listeria, that are critical to food safety.
      ABI showed significant (P < 0.05) microbial reduction during bioaerosol
      contamination (up to 5-log reduction of E. coli and Listeria), on chicken breast
      (approximately 1.3-log reduction of C. jejuni), on contact surfaces
      (approximately 3.9 log reduction of C. jejuni), and in liquid (2-log reduction of
      C. jejuni). Considering the stability of O(3), ease of use, and antimicrobial
      efficacy against foodborne pathogens, our results suggest that ABI is a better
      alternative, especially for meat and poultry processors, as compared to dry ice.
      Further, ABI can potentially serve as an additional processing hurdle to guard
      against pathogens during processing, transportation, distribution, and/or
      storage.

PMID- 23163946
TI  - Expression of hilA in response to mild acid stress in Salmonella enterica is
      serovar and strain dependent.
AB  - Salmonella enterica is the leading cause of foodborne illness with poultry and
      poultry products being primary sources of infection. The 2 most common S.
      enterica serovars associated with human infection are Typhimurium and
      Enteritidis. However, Kentucky and Heidelburg and the 2 most prevalent serovars
      isolated from poultry environments. Given the prevalence of other serovars in
      poultry products and environments, research is needed to understand virulence
      modulation in response to stress in serovars other than Typhimurium and
      Enteritidis. Thus, the objective of this research was to compare hilA gene
      expression (a master regulator of the virulence pathogenicity island) in response
      to acid stress among different strains and serovars of Salmonella. A total of 11
      serovars consisting of 15 strains of S. enterica were utilized for these
      experiments. Cultures were suspended in tryptic soy broth (TSB) adjusted to pH
      7.2, 6.2, or 5.5 with HCl or acetic acid. Total RNA was extracted from cultures
      at specific time points (0, 2, 4, and 24 h). Gene expression of hilA was measured
      with quantitative reverse transcriptase real time PCR (qRT-PCR). Growth and pH
      were measured throughout the 24 h time frame. Regulation of hilA in response to
      acid stress varied by serovar and strain and type of acid. The results of these
      experiments indicate that hilA regulation may have some impact on virulence and
      colonization of S. enterica. However, these results warrant further research to
      more fully understand the significance of hilA regulation in response to mild
      acid stress in S. enterica.

PMID- 23163947
TI  - Selection of dominant NSLAB from a mature traditional cheese according to their
      technological properties and in vitro intestinal challenges.
AB  - Isolates (47) of lactobacilli from 5 different productions of Melichloro cheese
      were examined for potential use as adjunct cultures. The sodium dodecyl sulfate
      polyacrylamide gel electrophoresis (SDS-PAGE) of whole-cell proteins classified
      29 isolates as L. paraplantarum and 18 as L. paracasei subsp. paracasei. Randomly
      amplified polymorphic DNA-polymerase chain reaction (RAPD-PCR) analysis
      differentiated the L. paraplantarum and L. paracasei subsp. paracasei isolates at
      strain level and both, RAPD analysis and whole-cell protein profiling provided
      useful information about the diversity of nonstarter lactic acid bacteria (NSLAB)
      in the different cheese productions. The isolates were slow acidifiers and about
      70% of them degraded, preferentially alpha(s)-casein. The amounts of amino acids
      accumulated in the milk increased with the incubation time. A similar enzyme
      profile was exhibited by strains of both species, except for alpha-mannosidase
      and alpha-fucosidase, which were not detected in the L. paracasei subsp.
      paracasei strains. All strains grew in the presence of bile at 0.3% and the
      majority was able to withstand pH 2.5 and pancreatin at 0.1%. Moreover, all
      strains reduced cholesterol in vitro, with higher removal ability recorded for
      strains of L. paraplantarum. A narrow spectrum of antibacterial activity was
      recorded for 88% of the strains. Selected isolates with appropriate technological
      and interesting in vitro intestinal challenges could be used as adjuncts and
      deserve further studies.

PMID- 23163948
TI  - Flavor comparison of natural cheeses manufactured in different countries.
AB  - The objective of this study was to determine the main flavor components of
      different natural aged cheese types from various countries and determine whether
      a unique sensory characteristic exists within specific countries for European
      cheeses. The flavor of 152 cheeses from Estonia, France, Italy, Germany, Holland,
      Austria, England, Greece, Ireland, Spain, Switzerland, Sweden, Belgium, and
      Denmark were described during 4 independent studies. The sensory data from these
      studies were combined. The cheeses were sorted according to milk type and
      texture, and flavor characteristics of these groups were described. The main
      flavor characteristics of the cheeses tested were salty, sweet, sour, astringent,
      biting, pungent, sharp, nutty, musty/earthy, dairy fat, buttery, and dairy sweet.
      The cluster analysis divided the cheeses into 4 clusters: clusters 1 and 2 were
      sour, dairy sour, salty, astringent, biting, and varied in buttery (cluster 1)
      and sharp notes (cluster 2). Cluster 1 and 2 were mainly composed of French
      cheeses, while clusters 3 and 4 represented cheeses from various countries.
      Cluster 3 and 4 were sweet, with cooked milk and nutty characteristics and varied
      from buttery (cluster 3) to sharp notes (cluster 4). Cheeses from some countries,
      for example, France and Estonia, generally exhibited common sensory
      characteristics within the specific country, but cheeses from some other
      countries, such as Italy, varied widely, and seemed to have no common sensory
      theme. Most regional cheese standards are not specific about flavor profiles and
      these results suggest it may be possible to start a further characterization of
      cheeses in some countries.

PMID- 23163949
TI  - Extending the shelf life of edible flowers with controlled release of 1
      methylcyclopropene and modified atmosphere packaging.
AB  - Edible flowers have great sensory appeal, but their extremely short shelf life
      limits their commercial usage. Postharvest 1-methylcyclopropene (1-MCP) treatment
      is used to counter ethylene activity and delay senescence in fresh produce;
      however, its potential application in edible flowers has not been tested. The
      objective of this study was to investigate the effect of 1-MCP treatment with
      modified atmosphere packaging (MAP) on the shelf life of edible flowers. Freshly
      harvested carnations and snapdragons were packaged in trays with or without 0.5
      MUL/L of 1-MCP, sealed with a gas permeable film, and stored at 5  degrees C.
      Package atmospheres, tissue electrolyte leakage, and flower quality were
      evaluated on days 0, 7, and 14. Treatment with 1-MCP resulted in significantly
      slower changes in package headspace O(2), CO(2), and C(2)H(4) partial pressures,
      maintained higher overall quality of both flower species and reduced electrolyte
      leakage and abscission in snapdragon. All samples prepared with MAP had
      significantly reduced dehydration and higher overall quality compared to flowers
      packaged commercially in plastic clamshell containers. Treatments with controlled
      release of 1-MCP and MAP significantly extended storage life of edible carnation
      and snapdragon flowers.

PMID- 23163950
TI  - In praise of editors, new and old.

PMID- 23163951
TI  - Symptomatology of autism spectrum disorder in a population with neurofibromatosis
      type 1.
AB  - AIM: Difficulties in neurocognition and social interaction are the most prominent
      causes of morbidity and long-term disability in children with neurofibromatosis
      type 1 (NF1). Symptoms of attention-deficit-hyperactivity disorder (ADHD) have
      also been extensively recognized in NF1. However, systematic evaluation of
      symptoms of autism spectrum disorder (ASD) in children with NF1 has been limited.
      METHOD: We present a retrospective, cross-sectional study of the prevalence of
      symptoms of ASD and ADHD and their relationship in a consecutive series of 66
      patients from our NF1 clinic. The Social Responsiveness Scale and the Vanderbilt
      ADHD Diagnostic Parent Rating Scale were used to assess symptoms of ASD and ADHD.
      RESULTS: Sixty-six participants (42 males, 24 females) were included in this
      study. Mean age at assessment was 10 years 11 months (SD 5 y 4 mo). Forty percent
      of our NF1 sample had raised symptom levels reaching clinical significance on the
      Social Responsiveness Scale (T >= 60), and 14% reached levels consistent with
      those seen in children with ASDs (T >= 75). These raised levels were not
      explained by NF1 disease severity or externalizing/internalizing behavioral
      disorders. There was a statistically significant relationship between symptoms of
      ADHD and ASD (chi(2) =9.11, df=1, p=0.003, phi=0.56). Particularly salient were
      the relationships between attention and hyperactivity deficits, with impairments
      in social awareness and social motivation. INTERPRETATION: We found that symptoms
      of ASD in our NF1 population were raised, consistent with previous reports.
      Further characterization of the specific ASD symptoms and their impact on daily
      function is fundamental to the development and implementation of effective
      interventions in this population, which will probably include a combination of
      medical and behavioral approaches.

PMID- 23163952
TI  - Activation of the reward system during sympathetic concern is mediated by two
      types of empathy in a familiarity-dependent manner.
AB  - Humans work to improve the situation of others through sympathetic concern. The
      empathic joy hypothesis proposes that the urge to help is stimulated by enhanced
      sensitivity to vicarious joy achieved through helping a recipient to meet their
      needs. We further hypothesized that the positive feeling-related brain activation
      that occurs in the striatum during sympathetic concern is enhanced by empathy in
      a familiarity-dependent manner. To test this, we conducted behavioral and
      functional magnetic resonance imaging experiments in which two participants
      simultaneously played a virtual ball-toss game where either the subjects' partner
      or an unfamiliar player was isolated by the other players. The subjects showed
      sympathetic behavior by tossing the ball to the isolated player and reported
      enhancement of self-positive feelings and anticipation of feeling improvements of
      the isolated player during sympathetic behaviors. Activation in the bilateral
      dorsal striatum became more prominent during the behaviors, supporting the
      empathic joy hypothesis. Dorsal striatal activity when helping a romantic partner
      positively correlated with affective empathic traits toward that partner, whereas
      the activity measured when helping a stranger positively correlated with
      perspective-taking traits. The correlation results further revealed a familiarity
      dependent empathic enhancement of positive feelings. Therefore, sympathetic
      concern is invoked through empathic positive feeling.

PMID- 23163953
TI  - Responses of anaerobic rumen fungal diversity (phylum Neocallimastigomycota) to
      changes in bovine diet.
AB  - AIMS: Anaerobic rumen fungi (Neocallimastigales) play important roles in the
      breakdown of complex, cellulose-rich material. Subsequent decomposition products
      are utilized by other microbes, including methanogens. The aim of this study was
      to determine the effects of dietary changes on anaerobic rumen fungi diversity.
      METHODS AND RESULTS: Altered diets through increasing concentrate/forage (50 : 50
      vs 90 : 10) ratios and/or the addition of 6% soya oil were offered to steers and
      the Neocallimastigales community was assessed by PCR-based fingerprinting with
      specific primers within the barcode region. Both a decrease in fibre content and
      the addition of 6% soya oil affected Neocallimastigales diversity within solid
      and liquid rumen phases. The addition of 6% soya oil decreased species richness.
      Assemblages were strongly affected by the addition of 6% soya oil, whereas
      unexpectedly, the fibre decrease had less effect. Differences in volatile fatty
      acid contents (acetate, propionate and butyrate) were significantly associated
      with changes in Neocallimastigales assemblages between the treatments.
      CONCLUSIONS: Diet clearly influences Neocallimastigales assemblages. The data are
      interpreted in terms of interactions with other microbial groups involved in
      fermentation processes within the rumen. SIGNIFICANCE AND IMPACT OF THE STUDY:
      Knowledge on the influence of diet on anaerobic fungi is necessary to understand
      changes in microbial processes occurring within the rumen as this may impact on
      other rumen processes such as methane production.

PMID- 23163954
TI  - Identification and profiling of novel microRNAs in the Brassica rapa genome based
      on small RNA deep sequencing.
AB  - BACKGROUND: MicroRNAs (miRNAs) are one of the functional non-coding small RNAs
      involved in the epigenetic control of the plant genome. Although plants contain
      both evolutionary conserved miRNAs and species-specific miRNAs within their
      genomes, computational methods often only identify evolutionary conserved miRNAs.
      The recent sequencing of the Brassica rapa genome enables us to identify miRNAs
      and their putative target genes. In this study, we sought to provide a more
      comprehensive prediction of B. rapa miRNAs based on high throughput small RNA
      deep sequencing. RESULTS: We sequenced small RNAs from five types of tissue:
      seedlings, roots, petioles, leaves, and flowers. By analyzing 2.75 million unique
      reads that mapped to the B. rapa genome, we identified 216 novel and 196
      conserved miRNAs that were predicted to target approximately 20% of the genome's
      protein coding genes. Quantitative analysis of miRNAs from the five types of
      tissue revealed that novel miRNAs were expressed in diverse tissues but their
      expression levels were lower than those of the conserved miRNAs. Comparative
      analysis of the miRNAs between the B. rapa and Arabidopsis thaliana genomes
      demonstrated that redundant copies of conserved miRNAs in the B. rapa genome may
      have been deleted after whole genome triplication. Novel miRNA members seemed to
      have spontaneously arisen from the B. rapa and A. thaliana genomes, suggesting
      the species-specific expansion of miRNAs. We have made this data publicly
      available in a miRNA database of B. rapa called BraMRs. The database allows the
      user to retrieve miRNA sequences, their expression profiles, and a description of
      their target genes from the five tissue types investigated here. CONCLUSIONS:
      This is the first report to identify novel miRNAs from Brassica crops using
      genome-wide high throughput techniques. The combination of computational methods
      and small RNA deep sequencing provides robust predictions of miRNAs in the
      genome. The finding of numerous novel miRNAs, many with few target genes and low
      expression levels, suggests the rapid evolution of miRNA genes. The development
      of a miRNA database, BraMRs, enables us to integrate miRNA identification, target
      prediction, and functional annotation of target genes. BraMRs will represent a
      valuable public resource with which to study the epigenetic control of B. rapa
      and other closely related Brassica species. The database is available at the
      following link: http://bramrs.rna.kr [1].

PMID- 23163955
TI  - Analysis of stress-induced duplex destabilization (SIDD) properties of
      replication origins, genes and intergenes in the fission yeast,
      Schizosaccharomyces pombe.
AB  - BACKGROUND: Replication and transcription, the two key functions of DNA, require
      unwinding of the DNA double helix. It has been shown that replication origins in
      the budding yeast, Saccharomyces cerevisiae contain an easily unwound stretch of
      DNA. We have used a recently developed method for determining the locations and
      degrees of stress-induced duplex destabilization (SIDD) for all the reported
      replication origins in the genome of the fission yeast, Schizosaccharomyces
      pombe. RESULTS: We have found that the origins are more susceptible to SIDD as
      compared to the non-origin intergenic regions (NOIRs) and genes. SIDD analysis of
      many known origins in other eukaryotes suggests that SIDD is a common property of
      replication origins. Interestingly, the previously shown deletion-dependent
      changes in the activities of the origins of the ura4 origin region on chromosome
      3 are paralleled by changes in SIDD properties, suggesting SIDD's role in origin
      activity. SIDD profiling following in silico deletions of some origins suggests
      that many of the closely spaced S. pombe origins could be clusters of two or
      three weak origins, similar to the ura4 origin region. CONCLUSION: SIDD appears
      to be a highly conserved, functionally important property of replication origins
      in S. pombe and other organisms. The distinctly low SIDD scores of origins and
      the long range effects of genetic alterations on SIDD properties provide a unique
      predictive potential to the SIDD analysis. This could be used in exploring
      different aspects of structural and functional organization of origins including
      interactions between closely spaced origins.

PMID- 23163956
TI  - Proton pump inhibitors: potential cost reductions by applying prescribing
      guidelines.
AB  - BACKGROUND: There are concerns that proton pump inhibitors (PPI) are being over
      prescribed in both primary and secondary care. This study aims to establish
      potential cost savings in a community drug scheme for a one year period according
      to published clinical and cost-effective guidelines for PPI prescribing. METHODS:
      Retrospective population-based cohort study in the Republic of Ireland using the
      Health Services Executive (HSE) Primary Care Reimbursement Services (PCRS)
      pharmacy claims database. The HSE-PCRS scheme is means tested and provides free
      health care including medications to approximately 30% of the Irish population.
      Prescription items are WHO ATC coded and details of every drug dispensed and
      claimants' demographic data are available. Potential cost savings (net ingredient
      cost) were estimated according to UK NICE clinical guidelines for all HSE-PCRS
      claimants on PPI therapy for >=3 consecutive months starting in 2007 with a one
      year follow up (n=167,747). Five scenarios were evaluated; (i) change to PPI
      initiation (cheapest brand); and after 3 months (ii) therapeutic switching
      (cheaper brand/generic equivalent); (iii) dose reduction (maintenance therapy);
      (iv) therapeutic switching and dose reduction and (v) therapeutic substitution
      (H2 antagonist). RESULTS: Total net ingredient cost was ?88,153,174 for claimants
      on PPI therapy during 2007. The estimated costing savings for each of the five
      scenarios in a one year period were: (i) ?36,943,348 (42% reduction); (ii)
      ?29,568,475 (34%); (iii) ?21,289,322 (24%); (iv) ?40,505,013 (46%); (v)
      ?34,991,569 (40%). CONCLUSION: There are opportunities for substantial cost
      savings in relation to PPI prescribing if implementation of clinical guidelines
      in terms of generic substitution and step-down therapy is implemented on a
      national basis.

PMID- 23163957
TI  - Oral health condition and treatment needs among young athletes with intellectual
      disabilities in Indonesia.
AB  - BACKGROUND: Data on the oral situation of young people with intellectual
      disabilities are scarce, especially data of children from a developing country.
      AIM: To describe and to evaluate the oral treatment needs of Special Olympics
      Special Smiles Athletes in Indonesia between 2004 and 2009. DESIGN: A cross
      sectional study data were collected through interviews and clinical examinations
      using the Special Olympics Special Smiles CDC protocol. PARTICIPANTS: Indonesian
      Special Smiles athletes; their mean age was 13.46 years +/- 2.97. RESULTS: More
      than 70% of athletes had visible untreated decay. Almost 30% (29.8%) of the
      athletes had gingival inflammation. Pain in the oral cavity was reported by
      28.6%. Athletes who had untreated decay reported 6.67 times (95% CI OR; 4.00
      11.14) more pain compared to those who did not have untreated decay. Athletes
      living in provinces on Java Island had 1.54 times (95% CI OR; 1.15-2.07) more
      untreated decay compared to the athletes who live in provinces in outer Java
      Island. 21.63% of the screened athletes were referred to the dentist for urgent
      treatment. CONCLUSION: The results suggest that there is an elevated oral
      treatment need in Indonesian Special Smiles population.

PMID- 23163958
TI  - Phosphatidylserine exposure on the surface of Leishmania amazonensis amastigotes
      modulates in vivo infection and dendritic cell function.
AB  - Leishmania amazonensis parasites can cause diverse forms of leishmaniasis in
      humans and persistent lesions in most inbred strains of mice. In both cases, the
      infection is characterized by a marked immunosuppression of the host. We
      previously showed that amastigote forms of the parasite make use of surface
      exposed phosphatidylserine (PS) molecules to infect host cells and promote
      alternative macrophage activation, leading to uncontrolled intracellular
      proliferation of the parasites. In this study, we demonstrated that treatment of
      infected mice with a PS-targeting monoclonal antibody ameliorated parasite loads
      and lesion development, which correlated with increased proliferative responses
      by lymphocytes. In addition, we observed an enhanced dendritic cell (DC)
      activation and antigen presentation in vitro. Our data imply that the recognition
      of PS exposed on the surface of amastigotes plays a role in down-modulating DC
      functions, in a matter similar to that of apoptotic cell clearance. This study
      provides new information regarding the mechanism of immune suppression in
      Leishmania infection.

PMID- 23163959
TI  - Olopatadine versus levocetirizine in chronic urticaria: an observer-blind,
      randomized, controlled trial of effectiveness and safety.
AB  - OBJECTIVES: Chronic urticaria (CU) is characterized by frequent appearance of
      wheals for >= 6 weeks. This study was undertaken to compare effectiveness and
      safety of olopatadine, a newer antihistamine with additional anti-inflammatory
      properties, in treating CU in comparison to the established second-generation
      antihistamine levocetirizine. METHODS: A single center, assessor-blind,
      randomized (1:1), active-controlled, parallel group, Phase IV trial
      (CTRI/2011/08/001965) was conducted with 120 adult CU patients of either sex.
      Subjects received either olopatadine (5 mg b.i.d.) or levocetirizine (5 mg/day)
      for 9 weeks, continuously for first 4 weeks and then on demand basis for last 5
      weeks. Primary outcome measures were urticaria activity score (UAS) and urticaria
      total severity score (TSS). Routine hematological and biochemical tests and
      treatment-emergent adverse events were monitored for safety. RESULTS: Data from
      54 subjects on olopatadine and 51 on levocetirizine were analyzed for
      effectiveness. UAS and TSS values declined significantly with both drugs over the
      treatment period but the reduction was greater with olopatadine. Adverse event
      profiles were comparable with sedation being the commonest complaint.
      CONCLUSIONS: Olopatadine is a safe and more effective alternative to
      levocetirizine in the treatment of CU.

PMID- 23163960
TI  - Intimate interactions with carbonyl groups: dipole-dipole or n->pi*?
AB  - Amide carbonyl groups in proteins can engage in C?O...C?O and C-X...C?O
      interactions, where X is a halogen. The putative involvement of four poles
      suggests that these interactions are primarily dipolar. Our survey of crystal
      structures with a C-X...C?O contact that is short (i.e., within the sum of the X
      and C van der Waals radii) revealed no preferred C-X...C?O dihedral angle.
      Moreover, we found that structures with a short X(-)...C?O contact display the
      signatures of an n->pi* interaction. We conclude that intimate interactions with
      carbonyl groups do not require a dipole.

PMID- 23163961
TI  - Improving quality of care among COPD outpatients in Denmark 2008-2011.
AB  - OBJECTIVE: To examine whether the quality of care among Danish patients with
      chronic obstructive pulmonary disease (COPD) has improved since the initiation of
      a national multidisciplinary quality improvement program. METHODS: We conducted a
      nationwide, population-based prospective cohort study using data from the Danish
      Clinical Register of COPD. Since 2008, the register has systematically monitored
      and audited the use of recommended processes of COPD care. RESULTS: Substantial
      improvements were observed for all processes of care and registration fulfillment
      increased to well above 85% for all indicators. Compared with 2008, a higher
      proportion of COPD outpatients in 2011 received annual measurements of the forced
      expiratory volume in 1 s in percent of predicted [relative risk (RR) 2.14, 95%
      confidence interval (CI), 2.09; 2.19], assessment of body mass index (RR 2.24,
      95% CI, 2.19; 2.29), assessment of dyspnea using the Medical Research Council
      scale (RR 2.25, 95% CI, 2.20; 2.31), registration of smoking status (RR 2.41, 95%
      CI, 2.35; 2.47), smoking cessation recommendation (RR 3.40, 95% CI, 3.18; 3.64)
      and offering of pulmonary rehabilitation (RR 2.78, 95% CI, 2.65; 2.90). Moderate
      variation in quality of care fulfillment between regions and hospital clinics
      still existed in 2011. The proportion of patients with mild to moderate COPD
      increased during the study period (P < 0.0001). CONCLUSION: Based on increased
      registration practice of important processes of care, the present study indicates
      a substantial improvement in the quality of care of COPD in Danish hospitals
      following the initiation of a national multidisciplinary quality improvement
      program in 2008. In the forthcoming years, it will be interesting to observe if
      this will translate into a better prognosis for Danish patients with COPD.

PMID- 23163962
TI  - A retrospective cohort study evaluating efficacy in high-risk patients with
      chronic lower extremity ulcers treated with negative pressure wound therapy.
AB  - The purpose of this study was to evaluate the efficacy of negative pressure wound
      therapy (NPWT) compared with standard of care on wound healing in high-risk
      patients with multiple significant comorbidities and chronic lower extremity
      ulcers (LEUs) across the continuum of care settings. A retrospective cohort study
      of 'real-world' high-risk patients was conducted using Boston University Medical
      Center electronic medical records, along with chart abstraction to capture
      detailed medical history, comorbidities, healing outcomes and ulcer
      characteristics. A total of 342 patients, 171 NPWT patients with LEUs were
      matched with 171 non-NPWT patients with respect to age and gender, were included
      in this cohort from 2002 to 2010. The hazard ratios (HRs) were estimated by COX
      proportional hazard models after adjusting for potential confounders. The NPWT
      patients were 2.63 times (95% CI = 1.87-3.70) more likely to achieve wound
      closure compared with non-NPWT patients. Moreover, incidence of wound closure in
      NPWT patients were increased in diabetic ulcers (HR = 3.26, 95% CI = 2.21-4.83),
      arterial ulcers (HR = 2.27, CI = 1.56-3.78) and venous ulcers (HR = 6.31, 95% CI
      = 1.49-26.6) compared with non-NPWT patients. In addition, wound healing appeared
      to be positively affected by the timing of NPWT application. Compared with later
      NPWT users (1 year or later after ulcer onset), early NPWT users (within 3 months
      after ulcer onset) and intermediate NPWT users (4-12 months after ulcer onset)
      were 3.38 and 2.18 times more likely to achieve wound healing, respectively. This
      study showed that despite the greater significant comorbidities, patients
      receiving NPWT healed faster. Early use of NPWT demonstrated better healing. The
      longer the interval before intervention is with NPWT, the higher the correlation
      is with poor outcome. 

PMID- 23163964
TI  - Preventing child marriages: first international day of the girl child "my life,
      my right, end child marriage".
AB  - On 17 November 2011, the United Nations General Assembly adopted a resolution
      (A/RES/66/170) designating 11 October as the first International Day of the Girl
      Child choosing ending child marriages as the theme of the day. Child marriage is
      a fundamental human rights violation and impacts all aspects of a girl's life.
      These marriages deny a girl of her childhood, disrupts her education, limits her
      opportunities, increases her risk of violence and abuse, and jeopardizes her
      health. The article presents data about the prevalence and effects, contributing
      factors and recommends action for prevention.

PMID- 23163965
TI  - Development of an automated method for Folin-Ciocalteu total phenolic assay in
      artichoke extracts.
AB  - We developed a system to run the Folin-Ciocalteu (F-C) total phenolic assay, in
      artichoke extract samples, which is fully automatic, consistent, and fast. The
      system uses 2 high performance liquid chromatography (HPLC) pumps, an
      autosampler, a column heater, a UV/Vis detector, and a data collection system. To
      test the system, a pump delivered 10-fold diluted F-C reagent solution at a rate
      of 0.7 mL/min, and 0.4 g/mL sodium carbonate at a rate of 2.1 mL/min. The
      autosampler injected 10 MUL per 1.2 min, which was mixed with the F-C reagent and
      heated to 65  degrees C while it passed through the column heater. The heated
      reactant was mixed with sodium carbonate and color intensity was measured by the
      detector at 600 nm. The data collection system recorded the color intensity, and
      peak area of each sample was calculated as the concentration of the total
      phenolic content, expressed in MUg/mL as either chlorogenic acid or gallic acid.
      This new method had superb repeatability (0.7% CV) and a high correlation with
      both the manual method (r(2) = 0.93) and the HPLC method (r(2) = 0.78). Ascorbic
      acid and quercetin showed variable antioxidant activity, but sugars did not. This
      method can be efficiently applied to research that needs to test many numbers of
      antioxidant capacity samples with speed and accuracy.

PMID- 23163963
TI  - NMR solution structure and condition-dependent oligomerization of the
      antimicrobial peptide human defensin 5.
AB  - Human defensin 5 (HD5) is a 32-residue host-defense peptide expressed in the
      gastrointestinal, reproductive, and urinary tracts that has antimicrobial
      activity. It exhibits six cysteine residues that are regiospecifically oxidized
      to form three disulfide bonds (Cys(3)-Cys(31), Cys(5)-Cys(20), and Cys(10)
      Cys(30)) in the oxidized form (HD5(ox)). To probe the solution structure and
      oligomerization properties of HD5(ox), and select mutant peptides lacking one or
      more disulfide bonds, NMR solution studies and analytical ultracentrifugation
      experiments are reported in addition to in vitro peptide stability assays. The
      NMR solution structure of HD5(ox), solved at pH 4.0 in 90:10 H(2)O/D(2)O, is
      presented (PDB: 2LXZ ). Relaxation T(1)/T(2) measurements and the rotational
      correlation time (tau(c)) estimated from a (15)N-TRACT experiment demonstrate
      that HD5(ox) is dimeric under these experimental conditions. Exchange broadening
      of the Halpha signals in the NMR spectra suggests that residues 19-21 (Val(19)
      Cys(20)-Glu(21)) contribute to the dimer interface in solution. Exchange
      broadening is also observed for residues 7-14 comprising the loop. Sedimentation
      velocity and equilibrium studies conducted in buffered aqueous solution reveal
      that the oligomerization state of HD5(ox) is pH-dependent. Sedimentation
      coefficients of ca. 1.8 S and a molecular weight of 14 363 Da were determined for
      HD5(ox) at pH 7.0, supporting a tetrameric form ([HD5(ox)] >= 30 MUM). At pH 2.0,
      a sedimentation coefficient of ca. 1.0 S and a molecular weight of 7079 Da,
      corresponding to a HD5(ox) dimer, were obtained. Millimolar concentrations of
      NaCl, CaCl(2), and MgCl(2) have a negligible effect on the HD5(ox) sedimentation
      coefficients in buffered aqueous solution at neutral pH. Removal of a single
      disulfide bond results in a loss of peptide fold and quaternary structure. These
      biophysical investigations highlight the dynamic and environmentally sensitive
      behavior of HD5(ox) in solution, and provide important insights into HD5(ox)
      structure/activity relationships and the requirements for antimicrobial action.

PMID- 23163966
TI  - What's so insidious about "Peace, Love, and Understanding"? A system
      justification perspective.
AB  - We agree that promoting intergroup harmony "carries insidious, often
      unacknowledged, 'system-justifying' consequences" (sect. 4.1.3, para. 2) and
      identify several ways in which "benevolent" and "complementary" stereotypes,
      superordinate identification, intergroup contact, and prejudice reduction
      techniques can undermine social change motivation by reinforcing system
      justifying beliefs. This may "keep the peace," but it also prevents individuals
      and groups from tackling serious social problems, including inequality and
      oppression.

PMID- 23163967
TI  - Hand sensation in adults with conservatively treated obstetric brachial plexus
      lesion.

PMID- 23163968
TI  - The physiological roles and metabolism of ascorbate in chloroplasts.
AB  - Ascorbate is a multifunctional metabolite in plants. It is essential for growth
      control, involving cell division and cell wall synthesis and also involved in
      redox signaling, in the modulation of gene expression and regulation of enzymatic
      activities. Ascorbate also fulfills crucial roles in scavenging reactive oxygen
      species, both enzymatically and nonenzymatically, a well-established phenomenon
      in the chloroplasts stroma. We give an overview on these important physiological
      functions and would like to give emphasis to less well-known roles of ascorbate,
      in the thylakoid lumen, where it also plays multiple roles. It is essential for
      photoprotection as a cofactor for violaxanthin de-epoxidase, a key enzyme in the
      formation of nonphotochemical quenching. Lumenal ascorbate has recently also been
      shown to act as an alternative electron donor of photosystem II once the oxygen
      evolving complex is inactivated and to protect the photosynthetic machinery by
      slowing down donor-side induced photoinactivation; it is yet to be established if
      ascorbate has a similar role in the case of other stress effects, such as high
      light and UV-B stress. In bundle sheath cells, deficient in oxygen evolution,
      ascorbate provides electrons to photosystem II, thereby poising cyclic electron
      transport around photosystem I. It has also been shown that, by supporting linear
      electron transport through photosystem II in sulfur-deprived Chlamydomonas
      reinhardtii cells, in which oxygen evolution is largely inhibited, externally
      added ascorbate enhances hydrogen production. For fulfilling its multiple roles,
      Asc has to be transported into the thylakoid lumen and efficiently regenerated;
      however, very little is known yet about these processes.

PMID- 23163969
TI  - EEG reveals an early influence of social conformity on visual processing in group
      pressure situations.
AB  - Humans are social beings and often have to perceive and perform within groups. In
      conflict situations, this puts them under pressure to either adhere to the group
      opinion or to risk controversy with the group. Psychological experiments have
      demonstrated that study participants adapt to erroneous group opinions in visual
      perception tasks, which they can easily solve correctly when performing on their
      own. Until this point, however, it is unclear whether this phenomenon of social
      conformity influences early stages of perception that might not even reach
      awareness or later stages of conscious decision-making. Using
      electroencephalography, this study has revealed that social conformity to the
      wrong group opinion resulted in a decrease of the posterior-lateral P1 in line
      with a decrease of the later centro-parietal P3. These results suggest that group
      pressure situations impact early unconscious visual perceptual processing, which
      results in a later diminished stimulus discrimination and an adaptation even to
      the wrong group opinion. These findings might have important implications for
      understanding social behavior in group settings and are discussed within the
      framework of social influence on eyewitness testimony.

PMID- 23163970
TI  - Implementation science in the real world: a streamlined model.
AB  - The process of quality improvement may involve enhancing or revising existing
      practices or the introduction of a novel element. Principles of Implementation
      Science provide key theories to guide these processes, however, such theories
      tend to be highly technical in nature and do not provide pragmatic nor
      streamlined approaches to real-world implementation. This paper presents a
      concisely comprehensive six step theory-based Implementation Science model that
      we have successfully used to launch more than two-dozen self-sustaining
      implementations. In addition, we provide an abbreviated case study in which we
      used our streamlined theoretical model to successfully guide the development and
      implementation of an HIV testing/linkage to care campaign in homeless shelter
      settings in Los Angeles County.

PMID- 23163971
TI  - Development and assessment of quality improvement education for medical students
      at The Ohio State University Medical Center.
AB  - This study tested the feasibility of a quality improvement (QI) program that
      provided first and second year medical students with education in QI processes
      and demonstrate their utility within the framework of a real-world QI project.
      Medical students assessed the use of the Surgical Safety Checklist at The Ohio
      State University Medical Center. Before performing audits students were required
      to complete a self-paced online program that provided preliminary education in
      QI, patient safety, leadership, teamwork, and patient-centered care. A 2.5-hr
      orientation introduced basic operating room protocol, and the surgical checklist
      audit tool. Orientation included a multimedia simulation of checklist usage and a
      role-playing exercise simulating its use. Students completed pre- and
      postparticipation assessments. Results included an increased knowledge of QI
      methodology, an improved understanding of the evidence supporting the need for QI
      projects within health systems, and a greater awareness of available QI projects.
      Students' perspectives changed to indicate an increased belief that QI is the
      responsibility of all health professionals including physicians, administrators
      and other staff. This study concluded that QI education can be effectively
      disseminated to medical students early in their education using existing online
      tools and experiential QI projects, and can result in actionable QI data
      supporting hospital improvement initiatives.

PMID- 23163972
TI  - Contextual and time dependent pain in fibromyalgia: an explorative study.
AB  - BACKGROUND: Little is known about contextual effects on chronic pain, and how
      vulnerability factors influence pain in different contexts. We wanted to examine
      if fibromyalgia (FM) pain varied between two social contexts, i.e. at home versus
      in a doctor office, when it was measured the same day, and if pain was stable for
      14 years when measured in similar contexts (doctor office). Our secondary aim was
      to explore if pain vulnerability factors varied in the two different contexts.
      FINDINGS: Fifty-five female FM patients were included in the study and scored
      pain in both contexts at baseline. Their age ranged between 21-68 years (mean
      45.7), mean education level was 11 years and mean FM-duration was 15.6 years.
      Their mean pain was perceived significantly lower at home than in a doctor
      context the same day. However, pain was much more stable when measured in two
      similar contexts 14 year apart where 30 subjects (54.5%) completed. Predictor
      analyses revealed that pain vulnerability factors apparently varied by home and
      doctor contexts. CONCLUSION: Pain and pain predictors seem to vary by contexts
      and time, with less pain at home than to a doctor the same day, but with
      unchanged pain in the same context after 14 years. Thus, contextual pain cues
      should be accounted for when pain is measured and treated, e.g. by focusing more
      on home-measured pain and by optimizing the doctor office context. This
      explorative study should be followed up by a larger full-scale study.

PMID- 23163973
TI  - Comprehensive dental evaluation of children with congenital or acquired heart
      disease.
AB  - OBJECTIVE: The aims of this case-control study were to (a) compare the caries
      experience and oral hygiene, and (b) quantify the persistence of a delay in the
      dental age in children with cardiac disease and a group of healthy children.
      METHODS AND MATERIALS: The study population comprised a group of 268 3- to 16
      year-old children and adolescents with a cardiac disease and a group of 268 age-
      and sex-matched healthy children and adolescents. Specifically, the decayed,
      missed, and filled teeth indices, simplified oral hygiene index, and the dental
      ages of the two groups of children were calculated and then compared. RESULTS:
      Although the oral health of the children with either a congenital or an acquired
      heart disease was the same as that of the healthy children, there were
      significant differences in the decayed, missed, and filled teeth indices. Dental
      ages of the children with a congenital heart disease were significantly lower
      than those of healthy children. The findings showed that complex univentricular
      heart diseases had the highest negative impact on dental development (21.1),
      followed by complex biventricular (20.9), simple surgical (20.5), and mild (20.4)
      heart disease patients. CONCLUSION: Once thorough knowledge of the child's
      cardiac status is gained, a definitive dental treatment plan for the child with a
      cardiac disease can be established.

PMID- 23163974
TI  - Diabetic retinopathy in patients with newly diagnosed type 2 diabetes mellitus in
      Jordan: prevalence and associated factors.
AB  - BACKGROUND: To determine the prevalence of diabetic retinopathy (DR) in patients
      with newly diagnosed type 2 diabetes mellitus (T2DM) in Jordan, as well as the
      factors associated with DR. METHODS: A cross-sectional study was conducted among
      127 consecutive newly diagnosed (within the past 6 months) patients with T2DM
      attending one of two diabetic care centers. Complete ocular examinations were
      performed by an ophthalmologist and relevant data were collected. A fundus
      examination was performed using slit lamp indirect ophthalmoscopy after pupillary
      dilation with 1% tropicamide drops, with DR defined and classified according to
      the scale developed by the Global Diabetic Retinopathy Project Group. RESULTS: Of
      all the patients examined, 7.9% had DR. Of those with DR, 40% already had
      clinically significant macular edema necessitating laser photocoagulation or
      intravitreal injections. Multivariate analysis revealed that age and HbA1c were
      significantly associated with DR. The odds of DR increased by 11% for each 1 year
      increase in age (odds ratio [OR] 1.11; 95% confidence interval [CI] 1.02-1.20).
      For each 1% increase in HbA1c, the odds of DR increased by 43% (OR 1.43; 95% CI
      1.09-1.88). CONCLUSIONS: Fewer than one-tenth of newly diagnosed Jordanian
      patients with T2DM had DR, but more than one-third of these patients had
      significant maculopathy. Therefore, early screening is strongly recommended for
      all newly diagnosed T2DM patients. Increased age and HbA1c values are associated
      with increased odds of DR. A study with a larger sample size is needed to
      elucidate the risk factors for DR in newly diagnosed T2DM.

PMID- 23163975
TI  - Stability of human mesenchymal stem cells during in vitro culture: considerations
      for cell therapy.
AB  - Ex vivo expansion and manipulation of human mesenchymal stem cells are important
      approaches to immunoregulatory and regenerative cell therapies. Although these
      cells show great potential for use, issues relating to their overall nature
      emerge as problems in the field. The need for extensive cell quantity
      amplification in vitro to obtain sufficient cell numbers for use, poses a risk of
      accumulating genetic and epigenetic abnormalities that could lead to sporadic
      malignant cell transformation. In this study, we have examined human mesenchymal
      stem cells derived from bone marrow, over extended culture time, using
      cytogenetic analyses, mixed lymphocyte reactions, proteomics and gene expression
      assays to determine whether the cultures would retain their potential for use in
      subsequent passages. Results indicate that in vitro cultures of these cells
      demonstrated chromosome variability after passage 4, but their immunomodulatory
      functions and differentiation capacity were maintained. At the molecular level,
      changes were observed from passage 5 on, indicating initiation of
      differentiation. Together, these results lead to the hypothesis that human
      mesenchymal stem cells cultures can be used successfully in cell therapy up to
      passage 4. However, use of cells from higher passages would have to be analysed
      case by case.

PMID- 23163977
TI  - Synthesis of the 1-monoester of 2-ketoalkanedioic acids, for example, octyl alpha
      ketoglutarate.
AB  - Oxidative cleavage of cycloalkene-1-carboxylates, made from the corresponding
      carboxylic acids, and subsequent oxidation of the resulting ketoaldehyde afforded
      the important 1-monoesters of 2-ketoalkanedioic acids. Thus ozonolysis of octyl
      cyclobutene-1-carboxylate followed by sodium chlorite oxidation afforded the 1
      monooctyl 2-ketoglutarate. This is a cell-permeable prodrug form of alpha
      ketoglutarate, an important intermediate in the tricarboxylic acid (TCA, Krebs)
      cycle and a promising therapeutic agent in its own right.

PMID- 23163976
TI  - A framework for organizing and selecting quantitative approaches for benefit-harm
      assessment.
AB  - BACKGROUND: Several quantitative approaches for benefit-harm assessment of health
      care interventions exist but it is unclear how the approaches differ. Our aim was
      to review existing quantitative approaches for benefit-harm assessment and to
      develop an organizing framework that clarifies differences and aids selection of
      quantitative approaches for a particular benefit-harm assessment. METHODS: We
      performed a review of the literature to identify quantitative approaches for
      benefit-harm assessment. Our team, consisting of clinicians, epidemiologists, and
      statisticians, discussed the approaches and identified their key characteristics.
      We developed a framework that helps investigators select quantitative approaches
      for benefit-harm assessment that are appropriate for a particular decisionmaking
      context. RESULTS: Our framework for selecting quantitative approaches requires a
      concise definition of the treatment comparison and population of interest,
      identification of key benefit and harm outcomes, and determination of the need
      for a measure that puts all outcomes on a single scale (which we call a benefit
      and harm comparison metric). We identified 16 quantitative approaches for benefit
      harm assessment. These approaches can be categorized into those that consider
      single or multiple key benefit and harm outcomes, and those that use a benefit
      harm comparison metric or not. Most approaches use aggregate data and can be used
      in the context of single studies or systematic reviews. Although the majority of
      approaches provides a benefit and harm comparison metric, only four approaches
      provide measures of uncertainty around the benefit and harm comparison metric
      (such as a 95 percent confidence interval). None of the approaches considers the
      actual joint distribution of benefit and harm outcomes, but one approach
      considers competing risks when calculating profile-specific event rates. Nine
      approaches explicitly allow incorporating patient preferences. CONCLUSION: The
      choice of quantitative approaches depends on the specific question and goal of
      the benefit-harm assessment as well as on the nature and availability of data. In
      some situations, investigators may identify only one appropriate approach. In
      situations where the question and available data justify more than one approach,
      investigators may want to use multiple approaches and compare the consistency of
      results. When more evidence on relative advantages of approaches accumulates from
      such comparisons, it will be possible to make more specific recommendations on
      the choice of approaches.

PMID- 23163978
TI  - Species-specific real-time PCR detection of Colletotrichum kahawae.
AB  - AIMS: Colletotrichum kahawae is a strongly aggressive pathogen causing coffee
      berry disease and is specific to Arabica coffee (Coffea arabica) in Africa. In
      this article, we developed a real-time PCR assay for the species-specific
      diagnosis of C. kahawae by designing the primers and a TaqMan probe derived from
      the single nucleotide polymorphism-rich region of glyceraldehyde-3-phosphate
      dehydrogenase (GAPDH) gene. METHODS AND RESULTS: DNA markers from rDNA internal
      transcribed spacer, actin, beta-tubulin and GAPDH genes of the ex-type culture of
      C. kahawae and 10 reference strains of Colletotrichum species were analysed for
      intra- and interspecific variations. The GAPDH gene was selected to develop a
      species-specific DNA marker. A TaqMan real-time PCR assay for species-specific
      detection of C. kahawae was developed, and its accuracy was tested against type
      strains of other phylogenetically closely related species in the C.
      gloeosporioides species complex, with the detection sensitivity of 80 fg MUl(-1)
      of genomic DNA. CONCLUSIONS: This real-time PCR assay is highly specific and
      sensitive for the diagnosis of C. kahawae and can be applied in qualitative and
      quantitative tests. SIGNIFICANCE AND IMPACT OF THE STUDY: This protocol allows
      for a rapid and sensitive detection of C. kahawae and will be useful in disease
      management and pest detection to prevent further spread of this pathogen.

PMID- 23163979
TI  - Is social exclusion pushing the Pakistani Hijras (Transgenders) towards
      commercial sex work? a qualitative study.
AB  - BACKGROUND: The Hijra is a distinct type of gender role in South Asia where men
      act like women. This group of people is socially excluded by the general
      community, in terms of attainment of an opportunity for a socially productive
      life. Often this sort of deprivation forces these individuals towards professions
      like sex trade, in pursuit of sustenance, which as a consequence places them as a
      key block in the puzzle of an impending generalized HIV epidemic in Pakistan.
      METHODS: This study is a qualitative study, which involved 8 in-depth interviews
      and four focus group discussions, conducted in Rawalpindi and Islamabad
      (Pakistan) from February to April 2012. The data was audio taped and transcribed.
      Key themes were identified and built upon. The respondents were contacted through
      a gate keeper Hijra who was a member of the hijra community. Multiple interview
      sessions were conducted with each respondent. RESULTS: Two key categories of the
      Hijras were identified as Khusrapan and Zananapan, during the in-depth interview
      sessions. This initial information paved way for the four focus group
      discussions. The data was presented using key themes which were identified. The
      study participants explained their life histories to us which made it obvious
      that they had been socially excluded at many stages of their lives from
      performing normal social functions. This lack of occupational and educational
      opportunities pushed them towards entering the risky business of selling sex.
      CONCLUSION: The transgender community is socially excluded by the Pakistani
      society which is leading them to indulge in commercial sex and putting their
      lives at risk. Prudent measures are needed to form community based organizations
      managed and led by hijra community and addressing their social exclusion and
      risky behaviors.

PMID- 23163980
TI  - Relevance of improved epidemiological knowledge to sustainable control of
      Haemonchus contortus in Nigeria.
AB  - Nigeria experiences losses in small ruminant production as a result of a high
      prevalence of infection with Haemonchus contortus, but there have been very few
      investigative studies into the epidemiology of H. contortus in Nigeria,
      particularly in the south and western parts of the country. For successful
      planning and execution of control of hemonchosis in Nigeria, there is a need for
      insight into the epidemiology of free-living stages under the prevailing local
      conditions and models for climatic and environmental factors that control the
      risk of hemonchosis and distribution of H. contortus. In this review, we assess
      previous studies on the epidemiology of H. contortus in Nigeria, evaluate the
      present climatic and epidemiological situation, and highlight areas that require
      further investigative studies. The goal is to identify factors that underpin
      better control strategies and holistic integrated farm-management practice.
      Previous studies on H. contortus provided important information for formulation
      of control strategies and development toward integrated parasite management.
      However, this review has revealed the need for holistic evaluation of the current
      epidemiology and prevalence of H. contortus in Nigeria, particularly in relation
      to climate change. Accurate information is needed to build useful predictive
      models of the population dynamics of all free-living stages, particularly the L3.

PMID- 23163981
TI  - Inferred calcification rate of a Mediterranean azooxanthellate coral is uncoupled
      with sea surface temperature along an 8 degrees  latitudinal gradient.
AB  - INTRODUCTION: Correlations between sea surface temperature (SST) and growth
      parameters of the solitary azooxanthellate Dendrophylliid Leptopsammia pruvoti
      were assessed along an 8 degrees  latitudinal gradient on western Italian coasts
      (Mediterranean Sea), to check for possible negative effects of increasing
      temperature as the ones reported for a closely related, sympatric but
      zooxanthellate species. RESULTS: Calcification rate was correlated with skeletal
      density but not with linear extension rate, indicating that calcium carbonate
      deposition was preferentially allocated to keep a constant skeletal density.
      Unlike most studies on both temperate and tropical zooxanthellate corals, where
      calcification rate is strongly related to environmental parameters such as SST,
      in the present study calcification rate was not correlated with SST. CONCLUSIONS:
      The lower sensitivity of L. pruvoti to SST with respect to other sympatric
      zooxanthellate corals, such as Balanophyllia europaea, may rely on the absence of
      a temperature induced inhibition of photosynthesis, and thus the absence of an
      inhibition of the calcification process. This study is the first field
      investigation of the relationship between SST and the three growth parameters of
      an azooxanthellate coral. Increasing research effort on determining the effects
      of temperature on biological traits of the poorly studied azooxanthellate
      scleractinians may help to predict the possible species assemblage shifts that
      are likely to occur in the immediate future as a consequence of global climatic
      change.

PMID- 23163982
TI  - A pilot study evaluating non-contact low-frequency ultrasound and underlying
      molecular mechanism on diabetic foot ulcers.
AB  - Non-contact low-frequency ultrasound (NCLF-US) devices have been increasingly
      used for the treatment of chronic non-healing wounds. The appropriate dose for
      NCLF-US is still in debate. The aims of this pilot study were to evaluate the
      relationship between dose and duration of treatment for subjects with non-healing
      diabetic foot ulcers (DFUs) and to explore the correlation between wound healing
      and change of cytokine/proteinase/growth factor profile. This was a prospective
      randomised clinical study designed to evaluate subjects with non-healing DFUs for
      5 weeks receiving standard of care and/or NCLF-US treatment. Subjects were
      randomly assigned to one of the three groups: application of NCLF-US thrice per
      week (Group 1), NCLF-US once per week (Group 2) and the control (Group 3) that
      received no NCLF-US. All subjects received standard wound care plus offloading
      for a total of 4 weeks. Percent area reduction (PAR) of each wound compared with
      baseline was evaluated weekly. Profiles of cytokines/proteinase/growth factors in
      wound fluid and biopsied tissue were quantified to explore the correlation
      between wound healing and cytokines/growth factor expression. Twelve DFU
      patients, 2 (16.7%) type 1 and 10 (83.3%) type 2 diabetics, with an average age
      of 58 +/- 10 years and a total of 12 foot ulcers were enrolled. Average ulcer
      duration was 36.44 +/- 24.78 weeks and the average ABI was 0.91 +/- 0.06. Group 1
      showed significant wound area reduction at weeks 3, 4 and 5 compared with
      baseline, with the greatest PAR, 86% (P < 0.05); Groups 2 and 3 showed 25% PAR
      and 39% PAR, respectively, but there were no statistically significant
      differences between Groups 2 and 3 over time. Biochemical and histological
      analyses indicated a trend towards reduction of pro-inflammatory cytokines (IL-6,
      IL-8, IL-1beta, TNF-alpha and GM-CSF), matrix metalloproteinase-9 (MMP-9),
      vascular endothelial growth factor (VEGF) and macrophages in response to NCLF-US
      consistent with wound reduction, when compared with control group subjects. This
      proof-of-concept pilot study demonstrates that NCLF-US is effective in treating
      neuropathic diabetic foot ulcers through, at least in part, inhibiting pro
      inflammatory cytokines in chronic wound and improving tissue regeneration.
      Therapeutic application of NFLU, thrice (3) per week, renders the best wound area
      reduction. 

PMID- 23163983
TI  - Insulin sensitivity, androgens and isotretinoin therapy in women with severe
      acne.
AB  - BACKGROUND: Androgens appear to play a role in the development of acne, and
      presence of acne is a potential marker of hyperandrogenism. OBJECTIVE: The
      authors evaluated androgens and insulin sensitivity markers before and after
      treatment with isotretinoin in women with post-adolescent severe acne who do not
      have hirsutism and/or ovulatory dysfunction. METHODS: Androgens, lipids, glucose
      and insulin levels were measured in 26 patients and 21 controls during oral
      glucose tolerance test. Homeostasis model assessment for insulin resistance, area
      under curve (AUC)glucose and AUCinsulin were calculated. Twenty patients
      completed a minimum of 6-month isotretinoin treatment. RESULTS: All studied
      parameters were similar in patients and controls at baseline. Isotretinoin
      therapy increased body mass index and triglyceride levels without any effect on
      androgens or insulin sensitivity. CONCLUSION: Severe acne itself is not
      associated with hyperandrogenemia and/or insulin resistance. Isotretinoin
      treatment does not alter serum androgens or insulin sensitivity, although it
      increases body weight and serum triglycerides.

PMID- 23163984
TI  - GPR30 regulates the EGFR-Akt cascade and predicts lower survival in patients with
      ovarian cancer.
AB  - OBJECTIVES: G protein-coupled receptor 30 (GPR30) is a 7-transmembrane estrogen
      receptor that functions alongside traditional estrogen receptors to regulate the
      cellular responses to estrogen. Recent studies suggest that GPR30 expression is
      associated with a poor prognosis, and that this is due to the GPR30-mediated
      transactivation of the EGFR in breast cancer. However, the biological
      contribution of GPR30 in ovarian cancer remains unclear. The purpose of this
      study was to elucidate the relationships between GPR30 expression and the
      clinicopathological findings, and to determine how the signaling cascade
      influences the prognosis of ovarian cancer. METHODS: The expression levels of
      GPR30, EGFR, ERalpha, and ERbeta were analyzed using an immunohistochemical
      analysis, and their correlations with the clinicopathological features were
      examined in 10 patients with borderline malignant tumors and 152 patients with
      epithelial ovarian cancer. We also examined whether GPR30 signaling activates the
      EGFR-Akt pathway in an ovarian cancer cell line (Caov-3) by a Western blotting
      analysis. RESULTS: The GPR30 expression in ovarian carcinomas was significantly
      higher than that in borderline malignancies (p=0.0016), and was not associated
      with the expression of the EGFR, ERalpha, or ERbeta. The expression of GPR30 in
      clear cell carcinomas was significantly lower than that in other subtypes of
      cancer (P <; 0.001). The expression of both GPR30 and EGFR was significantly
      associated with a poor prognosis in terms of the progression-free survival rate.
      The phosphorylation of the EGFR and Akt could be significantly enhanced by G1 (p
      <; 0.05) and inhibited by a Src family kinase inhibitor. CONCLUSION: The
      expression of both GPR30 and EGFR is associated with a poor outcome in ovarian
      cancer, and GPR30 increases the phosphorylation of Akt via the EGFR in ovarian
      cancer cells. The regulation of GPR30 might be a potentially useful new
      therapeutic target in ovarian cancer.

PMID- 23163986
TI  - Respiratory morbidity and growth after open thoracotomy or thoracoscopic repair
      of esophageal atresia.
AB  - BACKGROUND: Respiratory morbidity has been described in patients who underwent
      repair of esophageal atresia as a neonate. We compared the influence of open
      thoracotomy or thoracoscopy on lung function, respiratory symptoms, and growth.
      METHODS: Functional residual capacity (FRC(p)), indicative of lung volume, and
      maximal expiratory flow at functional residual capacity (V'max(FRC)), indicative
      of airway patency, of 37 infants operated for esophageal atresia were measured
      with Masterscreen Babybody at 6 and 12 months. SD scores were calculated for
      V'max(FRC). RESULTS: Repair was by thoracotomy in 21 cases (57%) and by
      thoracoscopy in 16 cases (43%). Lung function parameters did not differ between
      the types of surgery (FRC(p); P = .384 and V'max(FRC); P = .241). FRC(p) values
      were in the upper normal range and increased from 6 to 12 months (22.5 and 25.4
      mL/kg respectively, P = .010). Mean (SD) V'max(FRC) was below the norm without
      significant change in SD scores from 6 to 12 months (-1.9 and -2.3, respectively,
      P = .248). Neither lung function nor type of repair was associated with clinical
      evolution up to 2 years. CONCLUSION: Lung function during the first year was
      similar in EA infants repaired by thoracotomy or thoracoscopy. Ongoing follow-up
      including pulmonary function testing is needed to determine whether differences
      occur at a later age in this cohort.

PMID- 23163987
TI  - Using serial oxygenation index as an objective predictor of survival for
      antenatally diagnosed congenital diaphragmatic hernia.
AB  - INTRODUCTION: Best oxygenation index on day 1 (BOId1) had been shown to predict
      survival in congenital diaphragmatic hernia (CDH). Serial oxygenation index (OI)
      may enable better assessment of response to cardiorespiratory support than BOId1.
      METHODS: All antenatally diagnosed CDH from one tertiary neonatal unit were
      retrospectively reviewed. Oxygenation index at 6, 12, 24, and 48 hours from
      birth, as well as BOId1, were compared between survivors and nonsurvivors. The
      area under the curve and receiver operating characteristic (ROC) curves were used
      to compare serial OI within the first 24 hours and BOId1 between survivors and
      nonsurvivors. Statistical significance was set at P < .05. RESULTS: Twenty-four
      patients with CDH (13 survivors, 11 nonsurvivors) were included. Both groups were
      comparable in demographics and variables that could affect outcome. In terms of
      nonsurvival, ROC curve analysis demonstrated a sensitivity of 78% for serial OI
      greater than 252 and 56% for BOId1 greater than 8.5, both having a specificity of
      100%. The area under the ROC curve for serial OI and BOId1 were 0.96 and 0.85,
      respectively. The positive predictive value of serial OI (>252) and BOId1 (>11)
      for nonsurvival were both 100%, with an negative predictive value of 87% and 76%,
      respectively. CONCLUSIONS: Our preliminary study showed that serial OI in the
      first 24 hours of life is a good predictor of survival. It is simple to use and
      has the added advantage of assessing response to medical support in CDH. The
      results support the need for a large prospective study exploring the potential of
      serial OI to guide management and prognosis.

PMID- 23163988
TI  - Thirty-day outcome in children randomized to open and laparoscopic Nissen
      fundoplication.
AB  - BACKGROUND: Laparoscopic Nissen fundoplication (LNF) is considered by some to be
      superior to open Nissen fundoplication (ONF). To test this hypothesis, we
      compared early results after LNF and ONF in a randomized trial. METHODS: All
      children accepted for antireflux surgery for gastroesophageal reflux disease were
      offered enrollment. Ethical approval and parental consent were obtained.
      Anesthesia, surgical methods, and postoperative treatment were standardized.
      Patient demographics, length of hospital stay (LOS), and complications occurring
      the first 30 postoperative days were registered. RESULTS: Eighty-eight children
      were randomized to LNF (n = 44) or ONF (n = 44). The groups were comparable with
      regard to age, weight, and comorbidity. Duration of surgery was 150 +/- 34
      minutes for LNF and 89 +/- 25 minutes for ONF (P < .001). Median LOS was 7.0 days
      (range, 3-57 days) and 7.5 days (range, 2-20 days) after LNF and ONF,
      respectively (P = .74). Postoperative complications occurred in 48 patients, 24
      in both groups. Twenty-four patients (LNF: n = 12, ONF: n = 11) were readmitted
      to hospital because of complications occurring after discharge. CONCLUSIONS: This
      study failed to show that LNF is superior to ONF when surgery duration, LOS, and
      complications occurring during the first postoperative month were compared. Apart
      from surgery duration, the results were surprisingly similar.

PMID- 23163989
TI  - An animal model study for repair of tracheal defects with autologous stem cells
      and differentiated chondrocytes from adipose-derived stem cells.
AB  - BACKGROUND: Stenosis of trachea with mucosal and cartilage lesions is a
      challenging problem in tracheal surgery. Owing to ease of harvest and abundance,
      adipose-derived stem cells (ADSCs) are attractive and increasingly used in tissue
      engineering. The aim of this study was to evaluate the repair of trachea with
      autologous stem cells and differentiated chondrocytes from adipose-derived stem
      cells in an animal model. METHODS AND MATERIAL: Six canine ADSCs were isolated
      and proliferated in monolayer culture and CD44; CD90 markers were investigated by
      flow cytometry. ADSCs were seeded in alginate beads and were differentiated into
      chondrocytes by TGF-beta3. Cartilage-specific markers with reverse transcriptase
      polymerase chain reaction were demonstrated in differentiated cells. These
      differentiated cells and stem cells in alginate scaffold were separately
      transferred to a defect created in canine's trachea. After 8 weeks, the healing
      and cartilage formation in the trachea was evaluated by histological methods.
      RESULTS: We identified formed cartilage pieces and chondrocytes with lacuna and
      extracellular matrix in defects implanted with differentiated cells, but in other
      groups, staining of the sections did not show the presence of cartilage in the
      engineered tracheal wall. CONCLUSION: We showed that cartilage- engineered from
      differentiated adipose-derived stem cells in alginate biodegradable scaffold
      could repair tracheal cartilage defects.

PMID- 23163990
TI  - Diagnosis and treatment of tracheobronchial foreign bodies in 1024 children.
AB  - OBJECTIVE: This study sought to summarize the experience of diagnosis and
      treatment of tracheobronchial foreign bodies in children to effectively reduce
      complications and mortality. METHODS: The medical records of 1024 pediatric
      patients admitted to our hospital from January 1997 to September 2011 and
      diagnosed with clinically suspected tracheobronchial foreign body aspiration were
      retrospectively analyzed. RESULTS: Of the 1024 children patients, 674 were boys
      (65.8%) and 350 girls (34.2%). Two died of respiratory and circulatory failure
      (foreign bodies detected upon bronchoscopy but not retrieved) before surgery, 65
      patients underwent direct bronchoscopic removal of foreign bodies due to their
      critical status, and 957 received chest radiographs and chest fluoroscopy or
      multidetector spiral computed tomographic scans (941 positive). Foreign bodies
      were expectorated before surgery in 3 cases. There were 953 cases of
      bronchoscopically proven airway foreign body aspiration, with a diagnostic
      accuracy of 94.5%. Ninety-eight foreign bodies were lodged in the main bronchus
      and/or bilateral bronchi, 506 in the right main bronchus, and 349 in the left
      main bronchus. Atelectasis was noted in 42 patients, including 11 with pulmonary
      consolidation, whose lungs were re-expanded by endobronchial lavage and sputum
      aspiration. In 3 patients with bronchiectasis, conservative treatment following
      foreign body removal was followed by no improvement, and pulmonary lobectomy was
      performed. Foreign bodies were successfully extracted at the first bronchoscopic
      attempt in 948 cases, accounting for 99.7% of the total. However, 3 patients had
      to undergo another bronchoscopy to remove the foreign bodies. The most common
      types of foreign bodies were peanuts, melon seeds, and beans. CONCLUSIONS: Timely
      accurate diagnosis and treatment of tracheobronchial foreign bodies in children
      can avoid delay in treatment and effectively reduce complications and mortality.

PMID- 23163991
TI  - Predictors of posttraumatic growth among parents of children undergoing inpatient
      corrective surgery for congenital disease.
AB  - BACKGROUND/PURPOSE: Posttraumatic growth (PTG) is a positive psychological
      change, or benefit, as a result of a major life trauma and/or loss. The role of
      emotional intelligence (EI), social support, self-efficacy, posttraumatic stress
      symptoms (PTSS), and resilience in PTG was evaluated in parents of children
      undergoing a surgical procedure for congenital disease. METHODS: A questionnaire
      survey was conducted in 208 parents of children undergoing inpatient surgery for
      correction of congenital disease at the Departments of Pediatric Surgery, Qilu
      and Shandong Province Hospital, China, between May and September. Posttraumatic
      growth was measured using the Posttraumatic Growth Inventory. The study variables
      were measured using the Emotional Intelligence Scale, Perceived Social Support
      Scale, General Self-Efficacy Scale, Posttraumatic Stress Disorder Checklist
      Civilian Version, and the 10-item Connor-Davidson Resilience Scale, respectively.
      Hierarchical multiple regression analyses were used to identify the significant
      predictors. RESULTS: Posttraumatic growth was reported in 54.3% (113) of parents.
      Posttraumatic growth was positively associated with EI, self-efficacy,
      resilience, and PTSS (total P < .05). Social support was positively associated
      with the domain of relating to others in the Posttraumatic Growth Inventory (r =
      .208, P < .01). Hierarchical multiple regression analyses indicated EI was the
      main predictor of posttraumatic growth, whereas resilience and PTSS were the
      mediators of personal resources (EI and self-efficacy), perceived social support,
      and the growth. CONCLUSIONS: The relationship between PTG and other variables
      have been examined at only one point in time. Longitudinal studies in exploring
      the impact of EI and other variables affecting PTG can be used to reduce the
      impact of bidirectionality that may have impact on the conclusions drawn.
      Emotional management programs should focus on the use of EI as a proactive
      measure for enhancing emotional well-being and promoting positive emotions.

PMID- 23163992
TI  - Influence of location of delivery on outcome in neonates with gastroschisis.
AB  - BACKGROUND: It is not clear in the literature whether infants with a prenatal
      diagnosis of gastroschisis should be delivered in a perinatal center with level 3
      neonatal intensive care unit (NICU) and surgical facilities ("inborn") or if they
      could be safely delivered in a more local hospital and then transferred to a
      perinatal center ("outborn"). Our goal was to determine the impact of delivery
      site on outcomes for neonates diagnosed as having gastroschisis. METHODS: Data
      were obtained from the Canadian Pediatric Surgery Network, covering the years
      2005 to 2008 for 18 pediatric surgical centers. Inborn was defined as birth in a
      hospital with a NICU or connected to a NICU by a bridge or tunnel. Outborn was
      defined as requiring transfer by ambulance or flight. A P value less than .05 was
      considered significant. RESULTS: Of 395 infants with prenatally diagnosed
      gastroschisis, 237 were inborn and 158 were outborn. Univariate analysis
      demonstrated no significant difference between groups with respect to gestational
      age, birth weight, days on total parenteral nutrition, or length of hospital
      stay. There was a significant difference with regard to Score for Neonatal Acute
      Physiology-Version II, complication rates, comorbidities, and age at final
      closure. Logistic regression showed that location of delivery was a significant
      independent predictor for incidence of complications, as were Score for Neonatal
      Acute Physiology-Version II, comorbidities, and presence of bowel atresia or
      necrosis. The odds ratio of developing a complication when outborn was 1.6 (P =
      .05). CONCLUSIONS: Delivery outside a perinatal center is a significant predictor
      of complications for infants born with gastroschisis.

PMID- 23163993
TI  - Malrotation beyond infancy.
AB  - OBJECTIVE: The aim of this work was to study the various presentations of
      malrotation and management in patients older than 1 year. MATERIALS AND METHODS:
      Medical records of patients operated on over the last 6 years who were older than
      1 year with a diagnosis of intestinal malrotation were evaluated retrospectively.
      Data about age at presentation, sex, presenting symptoms, time to diagnosis,
      radiographic imaging performed, surgical intervention, complications, and
      postoperative follow-up were collected and evaluated. RESULTS: The study
      population included 35 children and 3 adults. About three-fourths of pediatric
      patients were younger than 5 years, and about half of these presented in the
      second year of life. All patients who presented in the second year of life had a
      classical presentation of malrotation. Older patients presented more commonly
      with atypical symptoms. Of these, 5 older children were previously treated for
      suspected diagnosis of abdominal tuberculosis. Two patients were referred for
      acute pancreatitis and 1 for severe gastroesophageal reflux disease. Three adults
      presented with acute small intestinal obstruction and were diagnosed to have
      malrotation intraoperatively. Upper gastrointestinal contrast study was
      diagnostic of malrotation in all pediatric patients. Ultrasound and color Doppler
      study of the abdomen revealed abnormal relationship of the superior mesenteric
      artery and vein in about one-third of the patients. All patients underwent a
      standard Ladd procedure. Midgut volvulus was present in about one-fourth of
      patients. Forty percent of patients with atypical presentation had persistence of
      preoperative symptoms postoperatively. Two adults developed complications
      postoperatively. There was no mortality in the present study. CONCLUSION:
      Malrotation should be suspected in all patients with varied acute or chronic
      abdominal symptoms, and the upper gastrointestinal contrast study should be
      conducted. If the existence of typical malrotation is confirmed, surgical
      correction is mandatory to avoid volvulus and intestinal obstruction
      independently of the patient's age.

PMID- 23163994
TI  - Management of gallstone disease in children: a new protocol based on the
      experience of a single center.
AB  - BACKGROUND/PURPOSE: Gallstones and cholelithiasis are being increasingly
      diagnosed in children owing to the widespread use of ultrasonography. The
      treatment of choice is cholecystectomy, and routine intraoperative
      cholangiography is recommended to explore the common bile duct. The objectives of
      this study were to describe our experience with the management of gallstone
      disease in childhood over the last 18 years and to propose an algorithm to guide
      the approach to cholelithiasis in children based on clinical and ultrasonographic
      findings. METHODS: The data for this study were obtained by reviewing the records
      of all patients with gallstone disease treated between January 1994 and October
      2011. The patients were divided into the following 5 groups based on their
      symptoms: group 1, asymptomatic; group 2, nonbiliary obstructive symptoms; group
      3, acute cholecystitis symptoms; group 4, a history of biliary obstructive
      symptoms that were completely resolved by the time of surgery; and group 5,
      ongoing biliary obstructive symptoms. Patients were treated according to an
      algorithm based on their clinical, ultrasonographic, and endoscopic retrograde
      cholangiopancreatography (ERCP) findings. RESULTS: A total of 223 patients were
      diagnosed with cholelithiasis, and comorbidities were present in 177 patients
      (79.3%). The most common comorbidities were hemolytic disorders in 139 patients
      (62.3%) and previous bariatric surgery in 16 (7.1%). Although symptoms were
      present in 134 patients (60.0%), cholecystectomy was performed for all patients
      with cholelithiasis, even if they were asymptomatic; the surgery was laparoscopic
      in 204 patients and open in 19. Fifty-six patients (25.1%) presented with
      complications as the first sign of cholelithiasis (eg, pancreatitis,
      choledocolithiasis, or acute calculous cholecystitis). Intraoperative
      cholangiography was indicated in 15 children, and it was positive in only 1
      (0.4%) for whom ERCP was necessary to extract the stone after a laparoscopic
      cholecystectomy (LC). Preoperative ERCP was performed in 11 patients to extract
      the stones, and a hepaticojejunostomy was indicated in 2 patients. There were no
      injuries to the hepatic artery or common bile duct in our series. CONCLUSIONS:
      Based on our experience, we can propose an algorithm to guide the approach to
      cholelithiasis in the pediatric population. The final conclusion is that LC
      results in limited postoperative complications in children with gallstones. When
      a diagnosis of choledocolithiasis or dilation of the choledocus is made, ERCP is
      necessary if obstructive symptoms persist either before or after an LC.
      Intraoperative cholangiography and laparoscopic common bile duct exploration are
      not mandatory.

PMID- 23163995
TI  - A rare microduplication in a familial case of annular pancreas and duodenal
      stenosis.
AB  - BACKGROUND/PURPOSE: We describe a 3-day-old male infant that was operated on for
      annular pancreas causing duodenal stenosis. The family history revealed that the
      mother also underwent surgery as a neonate owing to duodenal stenosis with an
      annular pancreas. The aim of our study was to perform molecular investigations in
      this rare and familial congenital malformation. METHODS: We performed high
      resolution (180 K) array comparative genomic hybridization using the infant's DNA
      and multiplex ligation-dependent probe amplification (MLPA) using the parents'
      and the affected mother's siblings' and parents' DNA. RESULTS: Array comparative
      genomic hybridization revealed previously unreported duplications on chromosome
      6q24.2 and 17q22-q23.1, respectively, in the infant's DNA, and the latter
      duplication was also found in the healthy father using MLPA, whereas the affected
      mother carried the 6q24 duplication (0.7 Mb) containing parts of the utrophin
      gene. We further performed MLPA analysis of the 6q24 region and found that the
      clinically unaffected grandfather was a carrier of the microduplication, and so
      were 2 asymptomatic siblings of the affected mother. CONCLUSIONS: The 6q24.2
      mircoduplication of the utrophin gene is a potential risk factor for the
      development of annular pancreas, but further studies will clarify the exact role
      and if this is a true risk factor or a rare normal variant.

PMID- 23163996
TI  - Characterization of endothelium-dependent relaxations in the mesenteric
      vasculature: a comparative study with potential pathophysiological relevance.
AB  - BACKGROUND: Endothelium-dependent relaxations in human adult mesenteric
      microvessels involve 3 different main mechanisms: cyclooxygenase (COX)-derived
      prostanoids, nitric oxide (NO), and endothelium-derived hyperpolarizing factor
      (EDHF), which elicits vascular smooth muscle hyperpolarization and relaxation.
      There are some pathological conditions with an abnormal balance between
      mesenteric vasoconstriction and vasodilatation inputs leading to endothelial
      dysfunction and tissue injury. PURPOSE: The purpose was to characterize the
      mechanisms mediating endothelium-dependent relaxation and differences in children
      and adult mesenteric microvessels. METHODS: Microvessels were dissected from
      omentum obtained from children (3-6 years old) and adults (25-41 years old) and
      mounted as ring preparations in a small vessel myograph. RESULTS: In microvessels
      precontracted with a thromboxane analogue, the endothelium-dependent relaxations
      to bradykinin (10 nmol/L to 30 MUmol/L) mediated by EDHF, that is, nonsensitive
      to COX (10 MUmol/L indomethacin) and NO synthase blockade (100 MUmol/L N-nitro-L
      arginine methyl ester), were higher in children than in adults. When EDHF was
      blunted by a depolarizing precontraction with KCl, the remaining COX- and NO
      dependent relaxations were significantly lower in children. CONCLUSIONS: The
      EDHF's role in the endothelium-dependent relaxations is higher in children's
      vasculature. This suggests that endothelial dysfunction in mesenteric
      microvessels in children is likely more dependent on EDHF-related mechanisms
      rather than on NO- or COX-derived prostanoids.

PMID- 23163997
TI  - Evaluation of omental inflammatory response with P-/E-selectin levels and
      histopathologic findings in experimental model.
AB  - AIM: The omentum plays a crucial role in abdominal defense mechanism by adhering
      to sites of inflammation and absorbing bacteria and debris from the peritoneal
      cavity. An experimental study was conducted to evaluate the inflammatory response
      of omentum in different abdominal events with omental P-/E-selectin levels and
      histopathologic findings. MATERIALS AND METHODS: Thirty Wistar rats were placed
      into 5 groups (n = 6), including a control group (CG), sham group (SG), bladder
      perforation (BP) group, splenic laceration (SL) group, and cecal ligation and
      puncture (CLP) group. Omental samples were obtained in CG after median
      laparotomy. In accordance with described models, BP, SL, and CLP were performed
      in experimental groups. Twenty-four hours after the first laparotomy,
      localization of the omental pad was noted, and omental samples were obtained for
      biochemical analysis of levels and histopathologic findings (no. of vessels in
      sections, polymorphic nuclear leukocytes [PMLs], lymphocytes). The mean P-/E
      selectin levels and histopathologic findings of inflammation were compared
      between groups. RESULTS: Although omentum was adhered to the cecum in all
      subjects after CLP, similar findings were not detected in other groups. P
      selectin and E-selectin levels and number of PML were significantly increased in
      the CLP group when compared with other groups (P < .05). The number of vessels in
      sections was significantly increased in CLP group when compared with SG and BP
      groups (P < .05), and the BP group had a decreased number of vessels than CG (P <
      .05). The number of PML was significantly increased in SG and SL and BP groups
      with respect to CG (P < .05). CONCLUSION: Among different experimental
      intraabdominal catastrophes, only CLP caused an inflammatory response and
      increased levels of adhesion molecules in the omentum. These findings suggest
      that the nature of the inflammation is the main determining factor for the
      omental function in intraabdominal events.

PMID- 23163998
TI  - Bacterial studies of complicated appendicitis over a 20-year period and their
      impact on empirical antibiotic treatment.
AB  - BACKGROUND: Multiresistant bacterial strains tend to develop, especially
      enterobacteriacae, in intraabdominal infections. The aim of this study was to
      characterize the evolution of the bacterial biota in complicated appendicitis in
      children over the past 20 years and their acquired resistance rates to
      antibiotics. MATERIALS AND METHODS: All pediatric patients admitted in the
      emergency unit for complicated appendicitis were retrospectively reviewed during
      3 periods: 1989 to 1991, 1999 to 2000, and 2009 to 2010. Results of peritoneal
      swabs were analyzed regarding bacterial species and resistance to antibiotics.
      Statistical significance was set at P < .05. RESULTS: Thirty-four, 48, and 85
      patients from the 3 periods, respectively, were included, with 1 to 6 bacterial
      strains found in each peritoneal sample. During the first period, 80% of the
      biota was composed of enterobacteriacae and anaerobes and then decreased to 65%,
      whereas streptococci levels increased from 0 to 22%. Pansusceptibility rates
      remained stable (17%, 16.8%, and 15.6% for the 3 periods, respectively).
      Piperacillin, vancomycin, ticarcillin-clavulanic acid, and fluoroquinolones were
      associated with increased resistance rates, unlike antibiotic associations
      currently used as postoperative treatments. CONCLUSION: No significant increase
      in resistance rates of bacteriacae in complicated appendicitis in children was
      found over the last 20 years. Empirical antibiotherapy protocols currently
      recommended remain efficient on this particular biota.

PMID- 23163999
TI  - Postoperative complications and health care use in children undergoing surgery
      for ulcerative colitis.
AB  - OBJECTIVES: Medical and surgical approaches toward children with ulcerative
      colitis (UC) vary and have differing implications for health care use. The goal
      of this study was to define hospital use and complications for children with UC
      before and after staged restorative proctocolectomy. PATIENTS AND METHODS: A
      retrospective study of the California Patient Discharge Dataset from 1999 to 2007
      of children aged 2 to 18 years with UC who underwent colectomy was performed (N =
      218). Surgical staging was determined alongside hospital type (children's vs non
      children's) and surgical case volume. Postoperative complications and hospital
      length of stay were analyzed using multivariate regression. RESULTS: The cohort
      was mostly male (56%) and white (80%), had private insurance (78%), and underwent
      colectomy at a children's hospital (62%). Overall, 65% required a separate
      hospital admission before admission for colectomy. Single-, 2-, and 3-stage
      procedures were performed in 19 (9%), 144 (66%), and 38 (17%) children. The mean
      admissions per patient were 1.8 +/- 2.4 before colectomy and 0.7 +/- 1.6 after
      surgical completion. Surgical complications occurred in 100 (49%) children, with
      39% being attributed to postoperative infection. Children with public insurance
      (odds ratio, 2.18; 95% confidence interval, 1.0-4.85) and those who underwent
      colectomy at a non-children's hospital (odds ratio, 2.53; 95% confidence
      interval, 1.0-6.37) had increased likelihood of surgical complications. Finally,
      nonwhite race, surgical staging, and undergoing colectomy at a low- or medium
      volume hospital resulted in prolonged hospitalization (P < .05). CONCLUSIONS:
      Children with UC who undergo colectomy use a large number of hospital resources
      before surgery and exhibit decreased hospital use after surgical completion.
      Children undergoing colectomy at children's and high-volume hospitals experience
      fewer surgical complications and shorter hospitalization.

PMID- 23164000
TI  - Ovarian torsion: diagnosis of inclusion mandates earlier intervention.
AB  - PURPOSE: The treatment of ovarian torsion (OT) is often delayed because of
      diagnostic uncertainty and dependence on radiologic confirmation. In contrast,
      when testicular torsion (TT) is suspected, diagnosis and management are expedited
      despite lack of certainty, and operative exploration is not delayed by radiologic
      investigations. We compared the management of torsion in both sexes to define a
      better clinical pathway for suspected OT. METHODS: A 2.5-year review of the
      Pediatric Health Information System database was performed to determine the
      incidence of TT and OT at large children's hospitals. A 10-year retrospective
      review of children (0-19 years) diagnosed with TT or OT at a single academic
      center was performed to identify differences in diagnosis and management and
      determine the impact on gonadal salvage rates. RESULTS: The incidence of TT was
      comparable with OT in the Pediatric Health Information System database (0.03% vs
      0.02%). A total of 158 patients with TT and 90 patients with OT were managed at
      our center with a median age of 12 years in both groups. Boys presented earlier
      after the onset of pain (36 vs 72 hours, P < .0001) and were imaged more quickly
      (0.77 vs 1.86 hours, P < .0001). Time to operating room (OR) was also shorter for
      TT (2.3 vs 6.3 hours, P < .0001). The salvage rate for TT was 30.3% vs 14.4% for
      OT (P < .01). CONCLUSIONS: Girls with suspected OT waited 2.5 times as long for
      diagnostic imaging and 2.7 times as long to be taken to the operating room. In
      addition, the gonadal salvage rate was significantly worse for girls compared
      with boys with TT. More urgent intervention for OT, with liberal use of
      diagnostic laparoscopy and without reliance on a definitive diagnosis by imaging,
      should be considered in girls with lower abdominal pain.

PMID- 23164002
TI  - Genitourinary rhabdomyosarcoma: lessons from a developing-world series.
AB  - OBJECTIVE: The objective was to retrospectively review a large series of
      pediatric patients with genitourinary rhabdomyosarcoma from a developing country.
      METHODS: A total of 49 children were treated over a 47-year period (1961-2008).
      Analysis of the clinical presentation, demographics, surgical records,
      histological results, and oncological management was performed. The patients were
      analyzed as a whole and also in 2 separate groups (pre- and post-1992). RESULTS:
      The median age at clinical presentation was 31/2 years. The majority (59%) of
      patients were Intergroup Rhabdomyosarcoma Study group 3, with locally advanced
      disease at presentation. Twenty (41%) of the 49 patients presented with primary
      tumors greater than 10 cm in diameter. Sixteen (33%) of the 49 patients had
      positive regional lymph nodes at presentation. The overall survival of the series
      was 30 (65%) of 46. The survival for those treated after 1992 in Intergroup
      Rhabdomyosarcoma Study group 3 was superior (P = .04) to those treated before
      1992 (80% vs 56%). CONCLUSION: Children in this large African series of
      genitourinary rhabdomyosarcoma present with greater locally advanced disease
      (node positive and bulky disease) when compared with the developed world.
      Improvements in the last 2 decades in local surgical and oncological care have
      led to an improvement in survival in children with locally advanced disease.

PMID- 23164001
TI  - Partial adrenalectomy minimizes the need for long-term hormone replacement in
      pediatric patients with pheochromocytoma and von Hippel-Lindau syndrome.
AB  - PURPOSE: Children with von Hippel-Lindau syndrome (VHL) are at an increased risk
      for developing bilateral pheochromocytomas. In an effort to illustrate the
      advantage of partial adrenalectomy (PA) over total adrenalectomy in children with
      VHL, we report the largest single series on PA for pediatric patients with VHL,
      demonstrating a balance between tumor removal and preservation of adrenocortical
      function. METHODS: From 1994 to 2011, a prospectively maintained database was
      reviewed to evaluate 10 pediatric patients with hereditary pheochromocytoma for
      PA. Surgery was performed if there was clinical evidence of pheochromocytoma and
      if normal adrenocortical tissue was evident on preoperative imaging and/or
      intraoperative ultrasonography. Perioperative data were collected, and patients
      were observed for postoperative steroid use and tumor recurrence. RESULTS: Ten
      pediatric patients with a diagnosis of VHL underwent 18 successful partial
      adrenalectomies (4 open, 14 laparoscopic). The median tumor size removed was 2.6
      cm (range, 1.2-6.5 cm). Over a median follow-up of 7.2 years (range, 2.6-15.8
      years), additional tumors in the ipsilateral adrenal gland were found in 2
      patients. One patient underwent completion adrenalectomy, and 1 underwent a
      salvage PA with resection of the ipsilateral lesion. One patient required short
      term steroid replacement therapy. At last follow-up, 7 patients had no
      radiographic or laboratory evidence of pheochromocytoma. CONCLUSION: At our
      institution, PA is the preferred form of management for pheochromocytoma in the
      (VHL) pediatric population. This surgical approach allows for removal of tumor
      while preserving adrenocortical function and minimizing the adverse effects of
      long-term steroid replacement on puberty and quality of life.

PMID- 23164003
TI  - The discovery of lymphatic stomata and its ultrastructure in mouse tunica
      vaginalis.
AB  - BACKGROUND/PURPOSE: The communicating hydrocele is caused by the failure of the
      processus vaginalis closure. After the patent processus vaginalis is closed, the
      hydrocele can subside spontaneously, but the mechanism responsible for the
      drainage of hydrocele has not been expounded. Former studies showed that
      lymphatic stomata between the mesothelial cells lining the peritoneum and pleura
      were responsible for the drainage of ascites and pleural effusion. Although the
      tunica vaginalis is also lined by mesothelial cells, the existence of lymphatic
      stomata in it has never been reported. Therefore, we investigated the presence
      and ultrastructure of lymphatic stomata in mouse tunica vaginalis. METHODS: We
      studied the ultrastructure of mouse tunica vaginalis by scanning and transmission
      electron microscopy. The submesothelial connective tissue with foramina were
      investigated after the mesothelial cells were digested by NaOH solution. Typan
      blue was used as a tracer to show the absorptive function of lymphatic stomata.
      RESULTS: The lymphatic stomata were found between the mesothelial cells. The
      trypan blue was directly absorbed by the lymphatic stomata. Milky spots which
      possessed immune function were observed, and the lymphatic stomata were found
      within the milky spots. CONCLUSION: Our study is the first to report the presence
      and ultrastructure of lymphatic stomata in mouse tunica vaginalis. They might be
      related to the lymphatic drainage in the tunica vaginalis cavity.

PMID- 23164004
TI  - Laparoscopic approach for inguinal hernia in children: resection without suture.
AB  - BACKGROUND/PURPOSE: The laparoscopic treatment of inguinal hernia in children
      presents a higher frequency of relapse when suture technique procedures are used.
      Here, we present an alternative technique consisting of laparoscopic resection of
      the hernia sac without suture according to the physiopathology of pediatric
      inguinal hernia. METHODS: In prospective studies from June 2006 to January 2011,
      pediatric patients with a diagnosis of inguinal hernia were subjected to surgery
      as follows: resection of the hernia sac without suture was performed with a 3
      port laparoscopic approach. Age, surgical time, recurrence, and complications
      were analyzed. RESULTS: We analyzed 285 patients, who ranged from 1 month to 15
      years old. They included 233 males, and 52 females. A percentage of 31.92 were
      bilateral (375 inguinal canals). The surgery time ranged from approximately 5 to
      12 minutes. They were followed up 6 to 55 months, with an optimal evolution in
      99.2%. Recurrence was observed in only 2 patients (0.53%), both of whom underwent
      incomplete resection. CONCLUSIONS: In this study, we demonstrate that resection
      of the hernia sac without sutures allows for the treatment of inguinal hernia
      with a low recurrence rate.

PMID- 23164005
TI  - Surgical treatment of perianal abscess and fistula-in-ano in childhood, with
      emphasis in children older than 2 years.
AB  - BACKGROUND: Anal sepsis in children ranges from perianal abscess to fistula-in
      ano. It is mostly observed in boys younger than 2 years. Most are treated
      conservatively. In contrast, anal sepsis in older children presents significant
      similarities to that of adults and is predominantly treated surgically. We report
      our outcomes after surgical treatment of anal abscess and fistula-in-ano in
      children older than 2 years. PATIENTS AND METHODS: Ninety-eight (98) children
      were operated on for anal abscess (46 patients; 47%) and/or fistula-in-ano (52
      patients; 53%). Incision and drainage of the abscess was performed as
      outpatients. In patients with fistulas, fistulotomy was the main treatment
      approach. All patients were healthy without risk factors for anal sepsis.
      RESULTS: In patients with anal abscess treated with incision and drainage, low
      recurrence (13%) or fistula formation rates were observed. Most anal fistulas
      were simple entities. Significant involvement of the anal sphincter was found in
      3 (6%) of 52 patients. An abscess cavity between the anal canal and the perianal
      skin was found in 4 (8%) of 52 patients, and an enlarged cryptic gland was found
      in 5 (10%) of 52 cases. Fistulotomy was performed in all patients with additional
      seton placement in 3 (6%) of 52 and a cryptotomy in 5 (10%) of 52 patients.
      CONCLUSIONS: Anal abscesses in children are easily treated by incision and
      drainage with low recurrence of perianal sepsis. Fistulas can be treated
      successfully in most patients with a fistulotomy, whereas complex fistulas are
      uncommon.

PMID- 23164006
TI  - The diagnosis and management of empyema in children: a comprehensive review from
      the APSA Outcomes and Clinical Trials Committee.
AB  - The aim of this study is to review the current evidence on the diagnosis and
      management of empyema. The American Pediatric Surgical Association Outcomes and
      Clinical Trials Committee compiled 8 questions to address. A comprehensive review
      was performed on each topic. Topics included the distinction between
      parapneumonic effusion and empyema, the optimal imaging modality in evaluating
      pleural space disease, when and how pleural fluid should be managed, the first
      treatment option and optimal timing in the management of empyema, the optimal
      chemical debridement agent for empyema, therapeutic options if chemical
      debridement fails, therapy for parenchymal abscess or necrotizing pneumonia and
      duration of antibiotic therapy after an intervention. The evidence was graded for
      each topic to provide grade of recommendation where appropriate.

PMID- 23164007
TI  - Treatment of necrotizing enterocolitis: an American Pediatric Surgical
      Association Outcomes and Clinical Trials Committee systematic review.
AB  - OBJECTIVE: The optimal treatment of necrotizing enterocolitis (NEC) is a common
      challenge for pediatric surgeons. Although many studies have evaluated prevention
      and medical therapy for NEC, few guidelines for surgical care exist. The aim of
      this systematic review is to review and evaluate the currently available evidence
      for the surgical care of patients with NEC. METHODS: Data were compiled from a
      search of PubMed, OVID, the Cochrane Library database, and Web of Science from
      January 1985 until December 2011. Publications were screened, and their
      references were hand-searched to identify additional studies. Clinicaltrials.gov
      was also searched to identify ongoing or unpublished trials. The American
      Pediatric Surgical Association Outcomes and Clinical Trials Committee proposed
      six questions deemed pertinent to the surgical treatment of NEC. Recent Cochrane
      Reviews examined three of these topics; a literature review was performed to
      address the additional three specific questions. RESULTS: The Cochrane Reviews
      support the use of prophylactic probiotics in preterm infants less than 2500
      grams to reduce the incidence of NEC, as well as the use of human breast milk
      rather than formula when possible. There is no clear evidence to support delayed
      initiation or slow advancement of feeds. For surgical treatment of NEC with
      perforation, there is no clear support of peritoneal drainage versus laparotomy.
      Similarly, there is a lack of evidence comparing enterostomy versus primary
      anastomosis after resection at laparotomy. There are little data to determine the
      length of treatment with antibiotics to prevent recurrence of NEC. CONCLUSION:
      Based on available evidence, probiotics are advised to decrease the incidence of
      NEC, and human milk should be used when possible. The other reviewed questions
      are clinically relevant, but there is a lack of evidence-based data to support
      definitive recommendations. These areas of NEC treatment would benefit from
      future investigation.

PMID- 23164008
TI  - Bilateral lower extremity acute thromboembolism as first presentation for cancer
      in a child: an interesting report.
AB  - Although it rarely occurs in children, acute arterial thromboembolism can cause
      significant morbidity and mortality. Rapid diagnosis and prompt treatment can
      increase the chances of survival with a functional limb. We describe the case of
      a 10-year-old boy with acute bilateral lower extremity ischemia due to arterial
      thromboemboli originating from a rare cancer. We discuss diagnosis of and
      treatment strategies for acute arterial thromboembolism in the pediatric
      population, as well as the rare cancer the patient was diagnosed with.

PMID- 23164009
TI  - Cardiac compression secondary to a massively dilated substernal colon conduit.
AB  - With the growing success of surgical repairs of congenital defects previously
      incompatible with life, it is expected of these patients to live longer and
      experience the complications of these corrective procedures. Esophageal atresia
      is a congenital defect that occurs in 1 out of 4000 births and is oftentimes a
      surgical emergency in which colonic conduits are routinely used for esophageal
      reconstruction. Colonic conduit redundancy and dilatation are well-recognized
      late complications of colon conduit surgeries for esophageal reconstructions. We
      report a rare case of symptomatic cardiac compression secondary to a massively
      dilated substernal colon conduit occurring 44 years after the initial childhood
      surgery in 1964 with rapid reversal of hemodynamic compromise after conduit
      removal.

PMID- 23164010
TI  - Laparoscopic resection of an intradiaphragmatic pulmonary sequestration: a case
      report and review of the literature.
AB  - Extralobar pulmonary sequestrations have been occasionally described in the
      abdomen but rarely in the diaphragm. We present the case of a 10 month old girl
      with an intradiaphragmatic pulmonary sequestration. The minimally invasive
      operative technique is outlined in detail, including the combine use of
      laparoscopy and thoracoscopy. The case is discussed and the literature is
      reviewed.

PMID- 23164011
TI  - Gastroschisis, ileal atresia, and Hirschsprung's disease in a newborn: the first
      reported case.
AB  - Gastroschisis and intestinal atresia are rare congenital gastrointestinal tract
      anomalies that coincide with each other in 5%-15% of cases. In contrast, there
      are only two reported cases of Hirschsprung's with simultaneous gastroschisis. We
      report the first case of gastroschisis, ileal atresia, and Hirschsprung's disease
      in a newborn. Despite the high morbidity and mortality associated with
      simultaneous congenital gastrointestinal tract anomalies, surgical management of
      these patients is feasible.

PMID- 23164012
TI  - Superior mesenteric artery syndrome after minimally invasive correction of pectus
      excavatum: impact of post-operative weight loss.
AB  - We report the case of a 14-year-old boy with pectus excavatum and mild scoliosis.
      The patient underwent a minimally invasive Nuss repair with excellent cosmetic
      result. He returned 3 weeks post-operatively with bilious emesis and a 3.6-kg
      weight loss (5.5% of total body weight). Radiographic evaluation was consistent
      with the diagnosis of superior mesenteric artery syndrome and the child
      ultimately required nasojejunal feedings. Following return to his baseline
      weight, he was transitioned to oral feedings and has done well in follow-up. This
      is the first report of SMA syndrome following minimally invasive pectus excavatum
      repair.

PMID- 23164013
TI  - Incomplete unilateral polyorchidism (bilobed testicle) mimicking testicular
      tumour.
AB  - Incomplete polyorchidism (also called bilobed testicle) is an extremely uncommon
      congenital anomaly. Only 3 cases of bilobed testicle were previously reported in
      the available literature. We describe a case of a 4-year-old boy who presented
      with a 6-month history of an asymptomatic scrotal mass located in the upper pole
      of the left testicle mimicking testicular tumour. After partial orchiectomy,
      macroscopic and pathological examination of the lesion confirmed the diagnosis of
      normal testicular tissue.

PMID- 23164014
TI  - Congenital sternal cleft.
AB  - We describe a rare case of congenital sternal cleft. Multidetector computed
      tomography showed the counterclockwise rotation of the heart. Primary surgical
      correction was successfully performed using the Sabiston technique when the
      patient was 20 days old. Although the circulatory and respiratory status was
      unstable in the immediate postoperative period, this abated, and the patient was
      discharged without complications on the 13th postoperative day. Postoperative
      multidetector computed tomography showed that the heart approached the normal
      position.

PMID- 23164015
TI  - Hepatic lobectomy and mucosectomy of intrahepatic cyst for type IV-A choledochal
      cyst.
AB  - OBJECTIVE: Excision of extrahepatic cyst with wide biliary-enteric anastomosis is
      the treatment of choice in choledochal cyst. The diseased mucosa of the residual
      cyst may be the cause for postoperative complications. Mucosectomy of the cyst
      wall may prevent such complications in type IV-A choledochal cyst. PATIENTS AND
      METHODS: Five cases (male:female, 3:2) of type IV-A choledochal cyst, aged
      between 15 and 120 months, are presented. The intrahepatic cyst was confined to
      only the left lobe in 1 patient and the left and part of the right lobe in 4
      patients. Excision of the extrahepatic cyst, left hemihepatectomy, mucosectomy of
      the residual intrahepatic cyst wall, and wide hepaticojejunostomy were done.
      RESULTS: Median hospital stay was 20 days. Postoperative biliary leak in 1
      patient stopped spontaneously after 3 weeks. Postoperative MRCP (magnetic
      resonance cholangiopancreatography) scan in 1 patient showed shrinkage of
      intrahepatic residual cyst and good biliary drainage. Liver function tests at 3
      months, 6 months, and at yearly intervals were within reference range in all
      patients. Cholangitis, hepatolithiasis, or malignancy was not noted in any of the
      patients. Median follow-up period was 36 months. CONCLUSION: Excision of the
      diseased mucosa from residual intrahepatic cyst wall may prevent long-term
      complications in patients with type IV-A choledochal cyst.

PMID- 23164016
TI  - Proximal hypospadias with small flat glans: the lateral-based onlay flap
      technique.
AB  - PURPOSE: The lateral-based onlay (LABO) technique for patients with proximal
      hypospadias associated with flat glans and report of the follow-up. MATERIALS AND
      METHODS: Between January 2004 and December 2010, the LABO technique was performed
      in 107 patients. The principle is to use the lateral foreskin adjacent to the
      glans as the onlay flap. Patient age ranged between 8 months and 2 years (mean,
      11 months). The records of 98 patients who maintained regular follow-up were
      reviewed. All the patients had proximal hypospadias with flat or incomplete cleft
      glans and did not have a deep chordee. Follow-up period ranged from 12 months to
      8 years (mean, 32 months). A transurethral silastic catheter was used for 7 days.
      RESULTS AND COMPLICATIONS: Satisfactory results were obtained in 93 patients
      (95%). Two children developed fistula, 2 developed glans dehiscence, and 1 child
      had skin prolapsing from the meatus that required excision. CONCLUSIONS: The LABO
      technique is a reliable technique for patients with proximal hypospadias in the
      absence of a deep chordee. It has particular value in patients with small or flat
      glans. With multiple layer closure and careful attention to technical details, a
      low complication rate (5%) was achieved in correcting this type of proximal
      hypospadias.

PMID- 23164017
TI  - A case of successful surgical repair for solid segment type pyloric atresia using
      a novel gastroduodenostomy procedure.
AB  - We present a case of successful surgical repair for solid segment type pyloric
      atresia using a novel gastroduodenal procedure.

PMID- 23164018
TI  - Surgical compliance with guidelines for paratesticular rhabdomyosarcoma (RMS).
      Data from the European Study on non-metastatic RMS.

PMID- 23164019
TI  - Re: Needle core vs open biopsy for diagnosis of intermediate- and high-risk
      neuroblastoma in children.

PMID- 23164021
TI  - Laparoscopic management of colonic complications in Ehlers-Danlos syndrome type
      IV.
AB  - Ehlers-Danlos syndrome type IV, also known as the vascular type, is the most
      severe form of the disease. It may cause spontaneous bowel perforation and
      rupture of major arteries. The treatment of bowel perforation in this population
      remains controversial because they are at risk for major wound complications
      owing to poor healing. We report the first use of laparoscopy in children with
      Ehlers-Danlos syndrome.

PMID- 23164022
TI  - Double H-type tracheoesophageal fistulas identified and repaired in 1 operation.
AB  - Isolated tracheoesophageal ("H-type") fistula is a relatively uncommon congenital
      anomaly that can be difficult to identify and, at times, challenging to repair.
      We present a very unusual case of an infant with 2 distinct H-type
      tracheoesophageal fistulas (TEFs) identified and repaired in 1 operation. A
      newborn male infant presented with coughing with feeds. Contrast esophagram
      demonstrated an intrathoracic H-type fistula without esophageal atresia. In the
      operating room, rigid bronchoscopy was performed, and a second TEF was identified
      in the cervical region. A separate balloon catheter was placed in each fistula.
      The intrathoracic fistula was repaired through a thoracotomy incision, and the
      more proximal fistula was repaired through a cervical incision. Each repair was
      uncomplicated, and recovery was uneventful. Double H-type tracheoesophageal
      appears to be extremely rare. This case underscores the importance of searching
      for a second fistula by bronchoscopy before undertaking definitive repair of a
      TEF.

PMID- 23164023
TI  - Stump appendicitis after childhood incidental appendectomy.
AB  - Stump appendicitis is a rare late complication of appendectomy. Most cases
      present months to years following surgery for acute appendicitis. Cases of stump
      appendicitis after incidental appendectomy are very rare. We present a case of
      stump appendicitis after incidental appendectomy during a procedure for duodenal
      obstruction as an infant.

PMID- 23164024
TI  - Brachial plexus palsy, a rare delayed complication of the Nuss procedure for
      pectus excavatum: a case report.
AB  - We report a rare complication after the Nuss procedure for the correction of
      pectus excavatum in a 15-year-old adolescent boy. He began to have delayed right
      brachial plexus injury on the 15th postoperative day. Careful physical check-up
      revealed a painful and enlarged subaxillary lymph node. He was successfully
      treated using anti-inflammatory medications and physical therapy.

PMID- 23164025
TI  - Wandering liver: ultrasound and magnetic resonance imaging diagnosis.
AB  - "Wandering liver" describes an excessive mobility of the liver caused by
      abnormalities of hepatic fixation that could lead to hepatic pedicle torsion or
      bowel obstruction. It is considered a rare entity, but because of the evolution
      in medical imaging techniques, this unusual condition is being identified more
      often. We report 2 cases presenting with chronic vague abdominal pain, diagnosed
      by abdominal ultrasonography and the use of cine-magnetic resonance imaging
      sequences with dynamic maneuvers. We tried to correlate our ultrasound and
      magnetic resonance imaging findings to peroperative findings and insist on the
      usefulness of dynamic maneuvers when confronted with atypical symptoms and a
      normal abdominal ultrasound scan finding.

PMID- 23164026
TI  - Management of pulse oximeter probe-induced finger injuries in children: report of
      two consecutive cases and review of the literature.
AB  - Pulse oximetry is a standard noninvasive procedure for monitoring arterial oxygen
      saturation. Finger injuries related to pulse oximeter use have been reported as
      chemical or thermal burns, sun-tanning, pressure erosion, sensory loss, and
      gangrene. The mechanisms of these complications have not been definitively
      explained; but pressure ischemia, prolonged use, overheating of the probe,
      inappropriate use of the probe, and short circuiting are considered to be the
      main factors. We describe 2 cases of pulse oximeter probe-induced finger
      injuries, propose the possible mechanisms and factors related to the injury, and
      discuss the management.

PMID- 23164027
TI  - Bilateral pharyngeal apparatus (branchial) sinuses in a set of identical twins--a
      case report.
AB  - Defective closure of the pharyngeal apparatus during the second week of gestation
      results in pharyngeal arch anomalies. Although pharyngeal apparatus (branchial)
      anomalies are frequently seen, bilateral cases are rare (only 2% to 3%).
      Bilaterality has a familial predisposition. Our patients, a set of identical
      twins, presented with bilateral discharging cervical sinuses noticed at 3 months
      of age. Physical examination was suggestive of bilateral pharyngeal apparatus
      (branchial) sinuses. Both patients were managed with surgical excision in the
      same operative sitting. To the best of our knowledge, ours is the first case of
      bilateral pharyngeal apparatus (branchial) sinuses in a set of identical twins.

PMID- 23164028
TI  - Endoscopic management of a duodenal duplication cyst.
AB  - Gastrointestinal duplications are rare congenital anomalies. Five percent to 10%
      of them are found in the duodenum. Traditionally, these lesions are treated
      surgically using either a laparoscopic or open transduodenal approach. We present
      the successful endoscopic treatment of a symptomatic duodenal duplication cyst in
      a 9-year-old girl.

PMID- 23164029
TI  - Forearm compartment syndrome owing to being stuck in the birth canal: a case
      report.
AB  - Neonatal compartment syndrome is a rare condition mainly involving the upper
      extremity associated with necrotic lesions. It is often initially misdiagnosed
      because the skin lesions mimic several other conditions of the newborn. Early
      diagnosis and timely intervention are of paramount importance to achieve the best
      outcome. In the present case, we describe a newborn with forearm compartment
      syndrome owing to being stuck in the birth canal.

PMID- 23164030
TI  - Pancreatic hydatid cyst masquerading as a choledochal cyst.
AB  - A 6-year-old boy presented with repeated attacks of fever, abdominal pain, and
      obstructive jaundice. Clinical examination and preoperative imaging suggested the
      diagnosis of a type I choledochal cyst. During surgery, a hydatid cyst was found
      occupying the head of pancreas, causing obstruction of the common bile duct. The
      authors emphasize that in endemic areas, hydatid cyst should be included in the
      list of conditions in the differential diagnoses of obstructive jaundice and
      cystic lesions located around the bilio-pancreatic junction in children.

PMID- 23164031
TI  - Hepatic mesenchymal hamartoma in a neonate with a Bochdalek diaphragmatic hernia:
      a case report.
AB  - The Bochdalek diaphragmatic hernia (BDH) is a common birth defect that is
      associated with other congenital malformations. Hepatic mesenchymal hamartoma
      (HMH) is the second most common benign hepatic tumor in children. The association
      between BDH and HMH or ectopic hepatic tissue is uncommon. We report a case of a
      female newborn with a left BDH that at surgery was incidentally found to have a
      tumor of 3.5 cm in maximum dimension with a serous muscular membrane. The
      histopathological study revealed vascular-mesenchymal stroma with bile ducts
      entrapped and peripheral normal hepatic tissue. These findings correlate with the
      diagnosis of hepatic mesenchymal hamartoma (HMH) in ectopic hepatic tissue. Our
      objective is to report a case of a rare association between HMH and BDH as well
      as discuss its differential diagnosis.

PMID- 23164032
TI  - Cystic mesenchymal hamartoma arising in intrathoracic heterotopic liver: a case
      report.
AB  - Intrathoracic heterotopic liver tissue is an exceedingly rare clinical entity. In
      most patients, it is associated with other congenital defects, including cardiac
      anomalies, congenital diaphragmatic hernia, pectus excavatum, and intralobar
      pulmonary sequestration. Although heterotopic liver could potentially lead to the
      same benign liver diseases that can affect the mother liver, the association of
      heterotopic liver tissue with tumors in childhood is extremely rare. We describe
      a unique case of cystic mesenchymal hamartoma arising from an intrathoracic
      heterotopic liver that was found incidentally during a diaphragmatic eventration
      repair. Association of ectopic liver tissue with mesenchymal hamartoma has not
      previously been reported in the literature.

PMID- 23164033
TI  - Chronic biloma after right hepatectomy for stage IV hepatoblastoma managed with
      Roux-en-Y biliary cystenterostomy.
AB  - We report the complex case of a 12-month-old girl with stage IV hepatoblastoma
      accompanied by thrombosis and cavernous transformation of the portal vein. After
      neoadjuvant chemotherapy, she underwent right hepatectomy, which was complicated
      by iatrogenic injury of her left hepatic duct, and subsequently developed a
      postoperative biloma and chronic biliocutaneous fistula. Concomitant with
      multiple percutaneous interventions to manage the biloma nonoperatively while the
      child completed her adjuvant chemotherapy, she progressed to develop chronic
      malnutrition, jaundice, and failure to thrive. Once therapy was completed and the
      child was deemed free of disease, she underwent exploratory laparotomy with Roux
      en-Y biliary cystenterostomy for definitive management, resulting in resolution
      of her biliary fistula, jaundice, and marked improvement in her nutritional
      status. Roux-en-Y biliary cystenterostomy is a unique and efficacious management
      option in the highly selected patient population with chronic biliary leak
      refractory to minimally invasive management.

PMID- 23164034
TI  - Transrectal small bowel evisceration after abdominal crush injury.
AB  - Transrectal small bowel evisceration (TSBE) is a rare entity that can occur after
      traumatic injuries. It has been described after impalement, sexual assault, blunt
      abdominal trauma, and swimming pool drain suction. The authors encountered such a
      case in a 4-year-old by following a crush abdominal injury. A laparotomy was
      performed. The eviscerated bowel was pulled inside the abdominal cavity,
      revealing the rectal perforation. A portion of devascularized ileum was resected,
      a primary bowel anastomosis was performed, and the longitudinal rectal laceration
      was repaired with a two-layered closure. There was no fecal soilage, and no
      protective colostomy was performed. The mortality and morbidity of TSBE are
      usually related with the severity and type of trauma. The mesenteric laceration
      and concomitant injuries can cause significant bleeding leading to a hemorrhagic
      shock and multiorgan failure.

PMID- 23164035
TI  - Finding a new normal: a grounded theory study of rehabilitation after treatment
      for upper gastrointestinal or gynaecological cancers--the patient's perspective.
AB  - This paper reports on a study of perspectives of rehabilitation needs by 33
      people treated for upper gastrointestinal and gynaecological cancers. This study
      used focus groups informed by grounded theory and involved adult participants who
      had completed radical treatment at a UK cancer centre. Patients were involved in
      the design. Findings indicate that these patients are likely to have ongoing
      rehabilitation needs and that there was poor awareness of possible treatment of
      symptoms and of rehabilitation services. Novel findings include distinct
      perspectives of adults who have completed treatment for upper gastrointestinal
      and gynaecological cancers regarding their rehabilitation needs. Patients on
      surgical pathways, or who had longer hospital stays, had a better understanding
      of the rehabilitation services available to them and they accessed them more
      easily to ameliorate their post-treatment symptoms. Furthermore rehabilitation
      services are not equally accessed by patients on different treatment pathways. A
      grounded theory of cancer rehabilitation was developed with core categories of:
      impacts on the person, adjustment after treatment, individualised tailored
      support and information sources. The overarching theme is 'seeking a new normal'.
      Individualised tailored support is integral to seeking and establishing a new
      normal. Routine assessment and referral for rehabilitation treatment warrants
      further evaluation in these groups.

PMID- 23164036
TI  - Not different is not the same as the same: how can we tell?

PMID- 23164037
TI  - Driving dangerously to save lives.

PMID- 23164038
TI  - Production and characterization of rhamnolipid biosurfactant from waste frying
      coconut oil using a novel Pseudomonas aeruginosa D.
AB  - AIM: To improve biosurfactant production economics by the utilization of
      potential low-cost materials. METHODS AND RESULTS: In an attempt to utilize cost
      effective carbon sources in the fermentative production of biosurfactants,
      various pure and waste frying oils were screened by a standard biosurfactant
      producing strain. Considering the regional significance, easy availability and
      the economical advantages, waste frying coconut oil was selected as the substrate
      for further studies. On isolation of more competent strains that could use waste
      frying coconut oil efficiently as a carbon source, six bacterial strains were
      isolated on cetyltrimethyl ammonium bromide-methylene blue agar plate, from a
      soil sample collected from the premises of a coconut oil mill. Among these,
      Pseudomonas aeruginosa D was selected as the potential producer of rhamnolipid.
      Spectrophotometric method, TLC, methylene blue active substance assay, drop
      collapse technique, surface tension measurement by Du Nouy ring method and
      emulsifying test confirmed the rhamnolipid producing ability of the selected
      strain and various process parameters were optimized for the production of
      maximum amount of biosurfactant. Rhamnolipid components purified and separated by
      ethyl acetate extraction, preparative silica gel column chromatography, HPLC and
      TLC were characterized by fast atom bombardment mass spectrometry as a mixture of
      dirhamnolipids and monorhamnolipids. The rhamnolipid homologues detected were Rha
      Rha-C(10) -C(10) , Rha-C(12) -C(10)  and Rha-C(10) -C(8) /Rha-C(8) -C(10) .
      CONCLUSION: These results indicated the possibility of waste frying coconut oil
      to be used as a very effective alternate substrate for the economic production of
      rhamnolipid by a newly isolated Ps. aeruginosa D. SIGNIFICANCE AND IMPACT OF THE
      STUDY: Results of this study throws light on the alternate use of already used
      cooking oil as high-energy source for producing a high value product like
      rhamnolipid. This would provide options for the food industry other than the
      recycling and reuse of waste frying oils in cooking and also furthering the value
      of oil nuts.

PMID- 23164039
TI  - Diagnostic value of respiratory virus detection in symptomatic children using
      real-time PCR.
AB  - BACKGROUND: Acute respiratory tract infections are an important public health
      problem. Sensitive and rapid diagnostic techniques have been developed and are
      used in daily clinical practice. Here we evaluate the clinical relevance of
      detecting 20 common respiratory pathogens by molecular methods in a general
      pediatric clinic. METHODS: Nasopharynx samples of children < 18 years of age with
      respiratory symptoms referred to a general pediatric clinic were tested for the
      presence of 19 viruses and Mycoplasma pneumoniae, using real-time polymerase
      chain reaction. RESULTS: Of 177 patients included in this retrospective study,
      73% were positive for at least one virus. Respiratory syncytial virus (36.6%) and
      human rhinovirus (24%) were most frequently detected. Patients in whom a
      respiratory virus or Mycoplasma pneumoniae was detected, were younger (6 versus
      24 months; p < 0.001) and more often hospitalized (116 versus 34; p = 0.001) than
      patients in whom no respiratory pathogen was detected. Also they were more likely
      to present with feeding problems, dyspnea, rhinorrhea and wheezing (all p < 0.05)
      than patients without a respiratory pathogen.In the majority of cases, clinicians
      did not change their antibiotic management after detecting a viral respiratory
      pathogen. No difference in mean Ct value was found between patients with one
      respiratory pathogen and those with >1 respiratory pathogen (30.5 versus 31.2; p
      = 0.573). CONCLUSION: Routine testing of common respiratory pathogens could lead
      to a better understanding of their role in disease in children with respiratory
      symptoms.

PMID- 23164040
TI  - Anthocyanins, but not anthocyanidins, from bilberry (Vaccinium myrtillus L.)
      alleviate pruritus via inhibition of mast cell degranulation.
AB  - We have previously reported that bilberry anthocyanins exhibit an anti-pruritic
      effect in a mouse model of allergic contact dermatitis. It has been reported that
      anthocyanins are particularly sensitive to thermal treatment and are easily
      hydrolyzed to anthocyanidins when exposed to high temperatures. The objective of
      this study was to compare the anti-pruritic effect of anthocyanin-rich quality
      controlled bilberry extract and anthocyanidin-rich degraded extract using a mouse
      model of allergic contact dermatitis. BALB/c mice with allergic contact
      dermatitis induced by 4 weeks of repeated application of 2,4,6-trinitro-1
      chlorobenzene (TNCB) were administered Bilberon-25 orally for 4 weeks after
      sensitization with TNCB. The effect of Bilberon-25 on pruritus was evaluated by
      measurement of scratching behavior. RBL-2H3 mast cells were used to investigate
      the effect of Bilberon-25 on degranulation in 48/80-stimulated mast cells.
      Compared with nonheated Bilberon-25, the proportion of anthocyanins in heated
      Bilberon-25 decreased, and the proportion of anthocyanidins was increased in
      heated-time dependent manner. Treatment with non-heated Bilberon-25 significantly
      attenuated the TNCB-induced increase in scratching behavior, whereas treatment
      with 2 h-heated Bilberon-25 did not. Moreover, 300 MUg/mL nonheated Bilberon-25
      showed significant inhibition of degranulation in RBL-2H3 mast cells, whereas 2 h
      heated Bilberon-25 had no effect at any concentration studied. It is assumed that
      the inhibitory effect of bilberry anthocyanins on pruritus might be mediated, at
      least in part, by its inhibitory effect on mast cell degranulation. In
      conclusion, the anthocyanin-rich but not anthocyanidin-rich bilberry extract may
      be a useful dietary supplement for skin diseases involving pruritic symptoms,
      such as chronic allergic contact dermatitis, atopic dermatitis, and rhinitis.

PMID- 23164041
TI  - Heterosexism, homonegativity, and the sociopolitical dangers of orthodox models
      of prejudice reduction.
AB  - Criticism of orthodox models of prejudice reduction is particularly relevant for
      lesbians, gay men, and bisexuals, particularly when considering stage models of
      coming-out. If social change is to be effected regarding endemic homonegativity
      and heterosexism, then it is argued that a radical rethink is needed to the
      understandable but misinformed desire to get us to like each other more.

PMID- 23164043
TI  - Synthesis of vertex-differentiated icosahedral closo-boranes: polyfunctional
      scaffolds for targeted drug delivery.
AB  - We report methods for the synthesis of vertex-differentiated icosahedral closo
      boranes. A single B-OH vertex of the icosahedral borane [closo-B(12)(OH)(12)](2-)
      was derivatized to prepare [closo-B(12)(OR)(OH)(11)](2-) using optimized
      alkylation conditions and purification procedures. Several representative vertex
      differentiated icosahedral closo-boranes were prepared utilizing carbonate ester
      and azide-alkyne click chemistries on the surface of the closo-B(12)(2-) core.

PMID- 23164042
TI  - Regional evidence of modulation of cardiac adiponectin level in dilated
      cardiomyopathy: pilot study in a porcine animal model.
AB  - BACKGROUND: The role of systemic and myocardial adiponectin (ADN) in dilated
      cardiomyopathy is still debated. We tested the regulation of both systemic and
      myocardial ADN and the relationship with AMP-activated protein kinase (AMPK)
      activity in a swine model of non-ischemic dilated cardiomyopathy. METHODS AND
      RESULTS: Cardiac tissue was collected from seven instrumented adult male minipigs
      by pacing the left ventricular (LV) free wall (180 beats/min, 3 weeks), both from
      pacing (PS) and opposite sites (OS), and from five controls. Circulating ADN
      levels were inversely related to global and regional cardiac function. Myocardial
      ADN in PS was down-regulated compared to control (p < 0.05), yet ADN receptor 1
      was significantly up-regulated (p < 0.05). No modifications of AMPK were observed
      in either region of the failing heart. Similarly, myocardial mRNA levels of
      PPARgamma, PPARalpha, TNFalpha, iNOS were unchanged compared to controls.
      CONCLUSIONS: Paradoxically, circulating ADN did not show any cardioprotective
      effect, confirming its role as negative prognostic biomarker of heart failure.
      Myocardial ADN was reduced in PS compared to control in an AMPK-independent
      fashion, suggesting the occurrence of novel mechanisms by which reduced cardiac
      ADN levels may regionally mediate the decline of cardiac function.

PMID- 23164044
TI  - The effect of problem-based learning in patient education after an event of
      CORONARY heart disease--a randomised study in PRIMARY health care: design and
      methodology of the COR-PRIM study.
AB  - BACKGROUND: Even though there is convincing evidence that self-care, such as
      regular exercise and/or stopping smoking, alters the outcomes after an event of
      coronary heart disease (CHD), risk factors remain. Outcomes can improve if core
      components of secondary prevention programmes are structurally and pedagogically
      applied using adult learning principles e.g. problem-based learning (PBL). Until
      now, most education programs for patients with CHD have not been based on such
      principles. The basic aim is to discover whether PBL provided in primary health
      care (PHC) has long-term effects on empowerment and self-care after an event of
      CHD. METHODS/DESIGN: A randomised controlled study is planned for patients with
      CHD. The primary outcome is empowerment to reach self-care goals. Data collection
      will be performed at baseline at hospital and after one, three and five years in
      PHC using quantitative and qualitative methodologies involving questionnaires,
      medical assessments, interviews, diaries and observations. Randomisation of 165
      patients will take place when they are stable in their cardiac condition and have
      optimised cardiac medication that has not substantially changed during the last
      month. All patients will receive conventional care from their general
      practitioner and other care providers. The intervention consists of a patient
      education program in PHC by trained district nurses (tutors) who will apply PBL
      to groups of 6-9 patients meeting on 13 occasions for two hours over one year.
      Patients in the control group will not attend a PBL group but will receive home
      sent patient information on 11 occasions during the year. DISCUSSION: We expect
      that the 1-year PBL-patient education will improve patients' beliefs, self
      efficacy and empowerment to achieve self-care goals significantly more than one
      year of standardised home-sent patient information. The assumption is that PBL
      will reduce cardiovascular events in the long-term and will also be cost
      effective compared to controls. Further, the knowledge obtained from this study
      may contribute to improving patients' ability to handle self-care, and
      furthermore, may reduce the number of patients having subsequent CHD events in
      Sweden. TRIAL REGISTRATION: NCT01462799.

PMID- 23164045
TI  - Is ability to hepatic steatosis influenced by age at the beginning of the
      overfeeding period in Muscovy and Pekin ducks?
AB  - The aim of this study was to analyse the effects of species (Muscovy and Pekin
      ducks) and age at the beginning of the overfeeding period on fatty liver
      production, carcass composition and lipid and moisture content of the liver and
      breast muscle. We reared four groups of 40 ducks per species for the study,
      starting at 2-week intervals in order to have four different ages together at the
      beginning of the overfeeding period (10, 12, 14 and 16 weeks). At the end of the
      overfeeding period, all ducks were slaughtered. Our results confirmed the high
      levels of difference in carcass composition and lipid content in the plasma,
      liver and breast muscle between Muscovy and Pekin ducks at all ages. Pekin ducks
      were not able to develop a high degree of hepatic steatosis, but had increased
      lipid storage in peripheral adipose and muscle tissues than Muscovy ducks.
      However, the fatty liver weight of Pekin ducks increased with age, with lipid
      deposition in the liver and peripheral tissues. The ability of Muscovy ducks to
      produce fatty livers remained unchanged with age in line, with lipid deposition
      in the liver and peripheral tissues. The sites of lipid deposition thus depend on
      species and not on the physiological maturity of ducks.

PMID- 23164046
TI  - A therapeutic approach for female, relapsing genital lichen sclerosus: a single
      center study.
AB  - OBJECTIVE: To assess the efficacy of methylprednisolone aceponate 0.1% (MPA 0.1%)
      in female genital lichen sclerosus (GLS) and efficacy of MPA, tacrolimus or
      emollient for prevention of flares. METHODS: A single-center, retrospective study
      was conducted. At baseline, female patients with relapsing GLS (n = 46) were
      treated with MPA 0.1% applied once daily for 8 weeks. Visual Analog Scale (VAS)
      score for vulvar pruritus and Investigator's Global Assessment (IGA) score were
      recorded at baseline, weeks 8 and 20. At week 8, patients responsive to treatment
      (n = 38) were further treated with MPA 0.1% twice weekly (n = 15), tacrolimus
      once daily (n = 13) or topical emollient once daily (n = 10), as maintenance
      therapy until week 20. RESULT: Both VAS and IGA median score was significantly
      decreased from baseline to week 8 (p = 0.000). At week 20, both median VAS and
      IGA scores differed significantly between patients treated with emollient and
      patients treated with MPA 0.1% (p = 0.000) and patients treated with emollient
      and patients treated with tacrolimus (p = 0.000); patients treated with MPA 0.1%
      presented no significant difference in either median VAS score (p = 0.032) or
      median IGA score (p = 0.636) at week 20 compared to patients treated with
      tacrolimus. CONCLUSIONS: MPA 0.1% is effective in relapsing female GLS. MPA 0.1%
      and tacrolimus have equal efficacy in preventing relapses.

PMID- 23164047
TI  - Markers of stem cells in human ovarian granulosa cells: is there a clinical
      significance in ART?
AB  - BACKGROUND: The purpose of the study was to determine the incidence of gene
      expression of Oct-4 and DAZL, which are typical markers for stem cells, in human
      granulosa cells during ovarian stimulation in women with normal FSH levels
      undergoing IVF or ICSI and to discover any clinical significance of such
      expression in ART. METHODS: Twenty one women underwent ovulation induction for
      IVF or ICSI and ET with standard GnRH analogue-recombinant FSH protocol.
      Infertility causes were male and tubal factor. Cumulus-mature oocyte complexes
      were denuded separately and granulosa cells were analyzed for each patient
      separately using quantitative reverse-transcription-polymerase chain reaction
      analysis for Oct-4 and DAZL gene expression with G6PD gene as internal standard.
      RESULTS: G6PD and Oct-4 mRNA was detected in the granulosa cells in 47.6%
      (10/21). The median of Oct-4 mRNA/G6PD mRNA was 1.75 with intra-quarteral range
      from 0.10 to 98.21. The OCT-4 mRNA expression was statistically significantly
      correlated with the number of oocytes retrieved; when the Oct-4 mRNA expression
      was higher, then more than six oocytes were retrieved (p=0.037, Wilcoxon rank
      sum). No detection of DAZL mRNA was found in granulosa cells. There was no
      additional statistically significant correlation between the levels of Oct-4
      expression and FSH basal levels or estradiol peak levels or dosage of FSH for
      ovulation induction. No association was found between the presence or absence of
      Oct-4 mRNA expression in granulosa cells and ovarian response to gonadotropin
      stimulation. Also, no influence on pregnancy was observed between the presence or
      absence of Oct-4 mRNA expression in granulosa cells or to its expression levels
      accordingly. CONCLUSIONS: Expression of OCT-4 mRNA, which is a typical stem cell
      marker and absence of expression of DAZL mRNA, which is a typical germ cell
      marker, suggest that a subpopulation of luteinized granulosa cells in healthy
      ovarian follicles (47.6%) consists of stem cells, which are not originated from
      primordial germ cells. Absence of Oct-4 gene expression in more than half of the
      cases means probably the end of the productive journey of these cells, towards
      the oocyte.

PMID- 23164048
TI  - Early life socio-economic position and later alcohol use: birth cohort study.
AB  - AIMS: To investigate associations between socio-economic position in early life
      and later alcohol use and problem use among male and female adolescents. DESIGN:
      Birth cohort study. SETTING: South West England. PARTICIPANTS: A total of 2711
      girls and 2379 boys with one or more measures of alcohol use or problem use at
      age 15 years. MEASUREMENTS: Exposure measures were highest parental social class,
      maternal education and household disposable income (all maternal self-report
      before school-age); outcome measures were heavy typical drinking, frequent
      drinking, regular binge drinking, alcohol-related psychosocial problems and
      alcohol-related behavioural problems. FINDINGS: Alcohol use and related problems
      were relatively common amongst adolescent girls and boys. Boys were slightly more
      likely to report frequent drinking and girls were slightly more likely to drink
      heavily and to experience alcohol-related psychosocial problems. Higher maternal
      education appeared protective in relation to alcohol-related problems,
      particularly among boys. Higher household income was associated with greater risk
      of alcohol use and problem use, most apparently among girls. CONCLUSIONS:
      Children from higher-income households in England appear to be at greater risk of
      some types of adolescent alcohol problems, and these risks appear different in
      girls compared to boys. Childhood social advantage may not generally be
      associated with healthier behaviour in adolescence.

PMID- 23164050
TI  - Treatment of postoperative cystoid macular oedema with dexamethasone intravitreal
      implant in a vitrectomized eye -- a case report.

PMID- 23164049
TI  - The alpha5 neuronal nicotinic acetylcholine receptor subunit plays an important
      role in the sedative effects of ethanol but does not modulate consumption in
      mice.
AB  - BACKGROUND: Alcohol use disorders (AUDs) are a major public health problem, and
      the few treatment options available to those seeking treatment offer only modest
      success rates. There remains a need to identify novel targets for the treatment
      of AUDs. The neuronal nicotinic acetylcholine receptors (nAChRs) represent a
      potential therapeutic target in the brain, as recent human genetic studies have
      implicated gene variants in the alpha5 nAChR subunit as high risk factors for
      developing alcohol dependence. METHODS: Here, we evaluate the role of the alpha5*
      nAChR for ethanol (EtOH)-mediated behaviors using male alpha5+/+ and alpha5-/-
      transgenic mice. We characterized the effect of hypnotic doses of EtOH and
      investigated drinking behavior using an adapted drinking-in-the-dark (DID)
      paradigm that has been shown to induce high EtOH consumption in mice. RESULTS: We
      found the alpha5 subunit to be important in mediating the sedative effects of
      EtOH. The alpha5-/- mice showed slower recovery from EtOH-induced sleep, as
      measured by loss of righting reflex. Additionally, the alpha5-/- mice showed
      enhanced impairment to EtOH-induced ataxia. We found the initial sensitivity to
      EtOH and EtOH metabolism to be similar in both alpha5+/+ and alpha5-/- mice.
      Hence, the enhanced sedation is likely due to a difference in the acute tolerance
      of EtOH in alpha5-/- mice. However, the alpha5 subunit did not play a role in
      EtOH consumption for EtOH concentrations ranging from 5 to 30% using the DID
      paradigm. Additionally, varenicline was effective in reducing EtOH intake in
      alpha5-/- mice. CONCLUSIONS: Together, our data suggest that the alpha5 nAChR
      subunit is important for the sedative effects of EtOH but does not play a role in
      EtOH consumption in male mice. Varenicline can be a treatment option even when
      there is loss of function of the alpha5 nAChR subunit.

PMID- 23164051
TI  - Malignant tumors of the penis.
AB  - BACKGROUND: Although penile cancer is rare in developed countries, it occurs more
      frequently in other parts of the world and causes significant morbidity and
      mortality. OBJECTIVE: To review the current literature on the pathogenesis, risk
      factors, clinical presentation, staging, and treatment of premalignant and
      malignant tumors of the penis. MATERIALS AND METHODS: A literature review using
      PubMed was conducted searching for articles on penile malignancies. RESULTS: The
      majority of penile cancers are in situ or invasive squamous cell carcinomas,
      although other rare tumors of the penis occur, such as melanoma, basal cell
      carcinoma, extramammary Paget's disease, and soft tissue sarcomas. CONCLUSION:
      Physicians should be aware of the risk factors and clinical presentation of
      penile malignancies because early diagnosis is essential in effective management
      and cure. Accurate staging is imperative for risk stratification and treatment
      planning. Depending on the type of tumor, size of tumor, location, staging, and
      grading, treatment modalities vary and may include topical chemotherapy, surgical
      excision, Mohs micrographic surgery, laser excision or ablation, systemic
      chemotherapy, and radiotherapy.

PMID- 23164052
TI  - The effect of massage on agitated behaviours in older people with dementia: a
      literature review.
AB  - AIMS AND OBJECTIVES: To review the literature on massage used to manage agitated
      behaviours in older people with dementia, assess its efficacy as a non
      pharmacological approach and provide recommendations for future research.
      BACKGROUND: Agitation has traditionally been managed with chemical or physical
      restraint. There has been a growing interest in complementary therapies such as
      massage. DESIGN: A literature review. METHODS:  Cooper's five-stage model of
      synthesising research guided the review process. The search terms 'massage',
      'agitation' and 'dementia' were defined, and 10 databases were searched in
      October 2011. No date limitations were applied, although searches were limited to
      articles written in English. For relevant records, full-text copies were obtained
      and assessed in terms of inclusion criteria and methodological quality using the
      Validity Rating Tool (VRT). Data were extracted using a form constructed with
      reference to the checklist of items to consider in data extraction, produced by
      the Cochrane Handbook for Systematic Reviews of Interventions. RESULTS: Thirteen
      studies met the inclusion criteria and were assessed on the VRT. One study was
      considered of adequate methodological quality to be included in the review. This
      prospective study found that massage significantly reduced levels of agitation in
      52 cognitively impaired residents in two long-term care facilities. CONCLUSIONS:
      There is a severe paucity of research that considers the effects of massage on
      managing agitated behaviours in older people with dementia. Whilst conclusions
      cannot be drawn from the one study included in this review, it did provide
      evidence to support the use of massage as a non-pharmacological approach to
      managing agitation in older people with dementia. More research, of better
      methodological quality, is needed. RELEVANCE TO CLINICAL PRACTICE: There is a
      need for health practitioners to be aware of the limited evidence for massage as
      an intervention for agitation and to provide opportunities to validate massage
      practice.

PMID- 23164053
TI  - Predisposing factors for involuntary culling in Holstein-Friesian dairy cows.
AB  - The objective was to identify predisposing factors for increased risk of
      involuntary culling in adult Holstein-Friesian dairy cows. Data were sourced from
      Scotland's Rural College (SRUC) Dairy Research Centre. Between September 2003 and
      August 2010 175 cows were culled, a herd culling rate of 33.7%. The major reasons
      for involuntary culling were fertility (27.4%) and udder problems (26.9%). In the
      analysis, the culled cows were matched with their cohorts that survived to a
      later lactation. To identify predisposing factors, a binary logistic model was
      applied. Cows with higher than average body condition score (BCS) at last service
      were five times [Odds Ratio (OR) = 4.8] more likely to be culled due to
      infertility. Cows with low protein yield on day 60 +/- 5 in lactation were ten
      times less likely (OR = 0.1) to be culled. In first lactation heifers, only BCS
      at last service increased the risk of involuntary culling due to infertility (OR
      = 13.0). A high milk yield acceleration was a significant (P = 0.04) factor in
      increasing the risk, five times (OR = 5.2) more, of culling cows due to udder
      problems. In conclusion, a high BCS at last service, high milk protein yield at
      around day 60 in lactation and acceleration of milk yield after calving exposed
      cows to a risk of being culled involuntarily. In practice, monitoring of traits
      that indicate metabolic imbalance could assist identifying cows at high risk of
      being culled and contribute to reducing the associated risk through a more
      effective timely decision.

PMID- 23164054
TI  - Identification and virulence of Chryseobacterium indologenes isolated from
      diseased yellow perch (Perca flavescens).
AB  - AIM: To identify pathogen of diseased yellow perch and determine their virulence.
      METHODS AND RESULTS: Fifteen Gram-negative bacterial isolates were recovered from
      the skin lesions of diseased yellow perch (Perca flavescens). Based on API 20NE
      test, ten isolates were found to share 67.2-99.9% homologies with
      Chryseobactertium indologenes. Based on fatty acid methyl ester analysis, 13
      isolates were found to share similarities with C. indologenes and other species
      of Chryseobacterium. Based on sequencing results of partial 16S rRNA gene, 13
      isolates shared 99% identities (e value = 2e-50) with the 16S rRNA sequence of C.
      indologenes (GenBank HQ259684). Based on the 16S-23S rRNA intergenic spacer
      region (ISR) sequence, the 13 isolates shared 88% identity (e value = 1e-165)
      with the 16S-23S ISR sequence of C. indologenes (GenBank EU014570). T-coffee
      multiple sequence alignment revealed that the partial 16S rRNA or the 16S-23S ISR
      sequence of the 13 isolates shared 100% identity with each other. When healthy
      yellow perch were exposed to the 15 isolates by bath immersion (c. 6 * 10(7) CFU
      ml(-1) for 1 h), only C. indologenes isolates killed 10-20% of fish, whereas
      other isolates were avirulent. When yellow perch were exposed to C. indologenes
      by intraperitoneal injection, mortality was dose dependent, with LD(50) and
      LD(95) values of 1.5 * 10(8) and 3.2 * 10(8) CFU per fish, respectively.
      CONCLUSIONS: Chryseobactertium indologenes could be pathogenic to yellow perch.
      SIGNIFICANCE AND IMPACT OF THE STUDY: This is the first report on the isolation
      of C. indologenes from diseased yellow perch. Virulence studies suggested that C.
      indologenes could become pathogenic to yellow perch.

PMID- 23164055
TI  - Improving panicle exsertion of rice cytoplasmic male sterile line by combination
      of artificial microRNA and artificial target mimic.
AB  - The adoption of hybrid rice caused the second leap in rice yield after the 'green
      revolution' and contributes substantially to food security of China and the
      world. However, almost all cytoplasmic male sterile lines (A lines) as females of
      hybrid rice have a natural deficiency of 'panicle enclosure', which blocks
      pollination between the A line and the fertility restorer line as the male (R
      line) of hybrid rice and decreases seed yield. In hybrid rice seed production,
      exogenous '920' (the active ingredient is gibberellin A3 ) must be applied to
      eliminate or alleviate panicle enclosure of the A line; however, this not only
      increases production cost and pollutes the environment, it also decreases seed
      quality. In this study, we designed a transgenic approach to improve plant height
      and panicle exsertion of the A line to facilitate hybrid rice production and
      maintain the semi-dwarf plant type of the hybrid. This approach comprising two
      components-artificial microRNA (amiRNA) and artificial target mimicry-can
      manipulate the differential expression of the endogenous Eui1 gene that is
      associated with rice internode elongation in the A line and the hybrid. amiRNA is
      a recently developed gene silencing method with high specificity, while target
      mimicry is a natural mechanism inhibiting the miRNA function that was also
      recently characterized. This approach provides a paradigm to tune the expression
      of endogenous genes to achieve the desired phenotype by combining amiRNA and
      artificial target mimicry technologies.

PMID- 23164056
TI  - Effect of salt reduction on growth of Listeria monocytogenes in meat and poultry
      systems.
AB  - Reducing sodium in food could have an effect on food safety. The objective was to
      determine differences in growth of Listeria monocytogenes in meat and poultry
      systems with salt substitutes. For phase 1, fresh ground beef, pork, and turkey
      with NaCl, KCl, CaCl(2), MgCl(2), sea salt, or replacement salt added at 2.0%
      were inoculated with L. monocytogenes to determine growth/survival during 5 d at
      4  degrees C to simulate a pre-blend process. L. monocytogenes populations
      significantly decreased (0.41 log CFU/g) during the storage time in beef, but no
      differences (P > 0.05) were observed over time in pork or turkey. Salt type did
      not affect (P > 0.05) L. monocytogenes populations during pre-blend storage.
      MgCl(2) and NaCl allowed significant growth of aerobic populations during
      storage. For phase 2, emulsified beef and pork products were processed with 2%
      NaCl, KCl, sea salt, or a NaCl/KCl blend and post-process surface-inoculated with
      L. monocytogenes to determine growth/survival at 4  degrees C for 28 d. Pork
      products showed significantly greater L. monocytogenes population growth at all
      sampling times (0, 7, 14, 21, and 28 d) than beef products, but salt type had no
      effect on L. monocytogenes populations with sampling times pooled for data
      analysis. Although salt types had no impact on L. monocytogenes populations in
      preblend and emulsified meat products, pork and turkey preblends and emulsified
      pork had greater L. monocytogenes populations compared with beef products. These
      studies demonstrate that sodium may not affect the safety of preblends and
      emulsified meat and poultry products.

PMID- 23164057
TI  - The dangers of prejudice reduction interventions: empirical evidence from
      encounters between Jews and Arabs in Israel.
AB  - This commentary focuses on Dixon et al.'s discussion on the dangers of employing
      prejudice-reduction interventions that seek to promote intergroup harmony in
      historically unequal societies. Specifically, it illustrates these dangers by
      discussing my work in Israel (now mentioned in Dixon et al.'s note 6) on the
      processes and practices through which reconciliation-aimed encounters between
      Jews and Arabs mitigate sociopolitical change.

PMID- 23164058
TI  - Mathematical outcomes and working memory in children with TBI and orthopedic
      injury.
AB  - This study compared mathematical outcomes in children with predominantly moderate
      to severe traumatic brain injury (TBI; n550) or orthopedic injury (OI; n547) at 2
      and 24 months post-injury. Working memory and its contribution to math outcomes
      at 24 months post-injury was also examined. Participants were administered an
      experimental cognitive addition task and standardized measures of calculation,
      math fluency, and applied problems; as well as experimental measures of verbal
      and visual-spatial working memory. Although children with TBI did not have
      deficits in foundational math fact retrieval, they performed more poorly than OIs
      on standardized measures of math. In the TBI group, performance on standardized
      measures was predicted by age at injury, socioeconomic status, and the duration
      of impaired consciousness. Children with TBI showed impairments on verbal, but
      not visual working memory relative to children with OI. Verbal working memory
      mediated group differences on math calculations and applied problems at 24 months
      post-injury. Children with TBI have difficulties in mathematics, but do not have
      deficits in math fact retrieval, a signature deficit of math disabilities.
      Results are discussed with reference to models of mathematical cognition and
      disability and the role of working memory in math learning and performance for
      children with TBI.

PMID- 23164060
TI  - Reversible generation of metastable enols in the 1,4-addition of thioacetic acid
      to alpha,beta-unsaturated carbonyl compounds.
AB  - Addition of thioacetic acid to reactive alpha,beta-unsaturated carbonyl compounds
      like acrolein or crotonaldehyde in acetone-d(6) generates metastable (E)- and (Z)
      1-alkenols, which tautomerize slowly at ambient temperature. The 1,4-addition of
      thioacetic acid and crotonaldehyde to (Z)-3-(acetylsulfanyl)-1-propen-1-ol is
      reversible with K(eq) = 5.5 +/- 0.5 L/mol. A concerted, cyclic 1,4-addition mode
      is proposed to explain the preferred (Z)-stereoselectivity in lower polarity,
      nonprotic solvents.

PMID- 23164059
TI  - Human immunodeficiency virus type 1 Vpu and cellular TASK proteins suppress
      transcription of unintegrated HIV-1 DNA.
AB  - BACKGROUND: Unintegrated HIV-1 DNA serves as transcriptionally active templates
      in HIV-infected cells. Several host factors including NF-kappabeta enhance HIV-1
      transcription. HIV-1 induced NF-kappabeta activation can be suppressed by viral
      protein U (Vpu). Interestingly HIV-1 Vpu shares amino acid homology with cellular
      Twik-related Acid Sensitive K+ (TASK) channel 1 and the proteins physically
      interact in cultured cells and AIDS lymphoid tissue. Furthermore, the first
      transmembrane domain of TASK-1 is functionally interchangeable with Vpu and like
      Vpu enhances HIV-1 release. RESULTS: Here we further characterize the role of
      TASK channels and Vpu in HIV-1 replication. We demonstrate that both TASK
      channels and Vpu can preferentially inhibit transcription of unintegrated HIV-1
      DNA. Interestingly, TASK-1 ion channel function is not required and suppression
      of HIV-1 transcription by TASK-1 and Vpu was reversed by overexpression of RelA
      (NF-kappabeta p65). CONCLUSION: TASK proteins and Vpu suppress transcription of
      unintegrated HIV-1 DNA through an NF-kappabeta-dependent mechanism. Taken
      together these findings support a possible physiological role for HIV-1 Vpu and
      TASK proteins as modulators of transcription of unintegrated HIV-1 DNA genomes.

PMID- 23164061
TI  - An expanded age range for meningococcal meningitis: molecular diagnostic evidence
      from population-based surveillance in Asia.
AB  - BACKGROUND: To understand epidemiologic patterns of meningococcal disease in
      Asia, we performed a retrospective molecular analysis of cerebrospinal fluid
      (CSF) specimens collected in prospective surveillance among children aged < 5
      years of age in China, South Korea, and Vietnam. METHODS: A total of 295 isolates
      and 2,302 CSFs were tested by a meningococcal species- and serogroup-specific
      polymerase chain reaction (PCR) assay targeting the Neisseria meningitidis (Nm)
      ctrA gene. Multi-locus sequence typing (MLST) was performed in Nm gene
      amplification analysis and incidence rates for meningococcal meningitis were
      estimated. RESULTS: Among 295 isolates tested, 10 specimens from Vietnam were
      confirmed as serogroup B and all were Sequence Type (ST) 1576 by MLST. Among the
      2,032 CSF specimen tested, 284 (14%) were confirmed by PCR (ctrA gene), including
      67 (23.6%) from China, 92 (32.4%) from Korea, and 125 (44.0%) from Vietnam.
      Neonates and infants aged < 6 months of age accounted for more than 50% of Nm-PCR
      positive CSF. Two CSF specimens from Vietnam were identified as serogroup B using
      MLST. In addition, 44 specimens underwent sequencing to confirm meningococcal
      serogroup; of these, 21 (48%) were serogroup C, 12 (27%) were serogroup X, 9
      (20%) were serogroup Y and 2 (5%) were serogroup B. The incidence rates of
      meningococcal meningitis among children < 5 years of age was highest in Vietnam
      (7.4/100,000 [95% CI, 3.6-15.3] followed by Korea (6.8/100,000 [95% CI, 3.5-13.5]
      and China (2.1/100,000) [95% CI, 0.7-6.2]). CONCLUSIONS: These results suggest
      that there is a previously undetected, yet substantial burden of meningococcal
      meningitis among infants and young children. Standardized, sensitive and specific
      molecular diagnostic assays with Nm serogrouping capacity are needed throughout
      Asia to understand the true burden of N. meningitidis disease.

PMID- 23164062
TI  - Implications of bio-efficacy and persistence of insecticides when indoor residual
      spraying and long-lasting insecticide nets are combined for malaria prevention.
AB  - BACKGROUND: Bio-efficacy and residual activity of insecticides used for indoor
      residual spraying (IRS) and long-lasting insecticide nets (LLINs) were assessed
      against laboratory-reared and wild populations of the malaria vector, Anopheles
      arabiensis in south eastern Tanzania. Implications of the findings are examined
      in the context of potential synergies and redundancies where IRS and LLINs are
      combined. METHODS: Bioassays were conducted monthly for six months on three LLIN
      types (Olyset(r) PermaNet 2.0(r),and Icon Life(r)) and three IRS treatments (2
      g/m2 pirimiphos-methyl, 2 g/m2 DDT and 0.03 g/m2 lambda-cyhalothrin, sprayed on
      mud walls and palm ceilings of experimental huts). Tests used susceptible
      laboratory-reared An. arabiensis exposed in cones (nets and IRS) or wire balls
      (nets only). Susceptibility of wild populations was assessed using WHO diagnostic
      concentrations and PCR for knock-down resistance (kdr) genes. RESULTS: IRS
      treatments killed >= 85% of mosquitoes exposed on palm ceilings and >= 90% of
      those exposed on mud walls, but up to 50% of this toxicity decayed within 1-3
      months, except for DDT. By 6th month, only 7.5%, 42.5% and 30.0% of mosquitoes
      died when exposed to ceilings sprayed with pirimiphos-methyl, DDT or lambda
      cyhalothrin respectively, while 12.5%, 36.0% and 27.5% died after exposure to mud
      walls sprayed with the same insecticides. In wire-ball assays, mortality
      decreased from 98.1% in 1st month to 92.6% in 6th month in tests on PermaNet
      2.0(r), from 100% to 61.1% on Icon Life(r) and from 93.2% to 33.3% on Olyset(r)
      nets. In cone bioassays, mortality reduced from 92.8% in 1st month to 83.3% in
      6th month on PermaNet 2.0(r), from 96.9% to 43.80% on Icon Life(r) and from 85.6%
      to 14.6% on Olyset(r). Wild An. arabiensis were 100% susceptible to DDT, 95.8% to
      deltamethrin, 90.2% to lambda cyhalothrin and 95.2% susceptible to permethrin. No
      kdr gene mutations were detected. CONCLUSIONS: In bioassays where sufficient
      contact with treated surfaces is assured, LLINs and IRS kill high proportions of
      susceptible An. arabiensis mosquitoes, though these efficacies decay gradually
      for LLINs and rapidly for IRS. It is, therefore, important to always add intact
      nets in sprayed houses, guaranteeing protection even after the IRS decays, and to
      ensure accurate timing, quality control and regular re-spraying in IRS
      programmes. By contrast, adding IRS in houses with intact LLINs is unlikely to
      improve protection relative to LLINs alone, since there is no guarantee that
      unfed vectors would rest long enough on the sprayed surfaces, and because of the
      rapid IRS decay. However, there is need to clarify these effects using data from
      observations of free flying mosquitoes in huts. Physiological susceptibility of
      An. arabiensis in the area remains 100% against DDT, but is slightly reduced
      against pyrethroids, necessitating caution over possible spread of resistance.
      The loss of LLIN toxicity, particularly Olyset(r) nets suggests that protection
      offered by these nets against An. arabiensis may be primarily due to physical
      bite prevention rather than insecticidal efficacy.

PMID- 23164063
TI  - Deficits in social perception in opioid maintenance patients, abstinent opioid
      users and non-opioid users.
AB  - AIMS: This study aimed to compare emotion perception and social inference in
      opioid maintenance patients with abstinent ex-users and non-heroin-using
      controls, and determine whether any deficits in could be accounted for by
      cognitive deficits and/or risk factors for brain damage. DESIGN: Case-control.
      SETTING: Sydney, Australia. PARTICIPANTS: A total of 125 maintenance patients
      (MAIN), 50 abstinent opiate users (ABST) and 50 matched controls (CON).
      MEASUREMENTS: The Awareness of Social Inference Test (TASIT) was used to measure
      emotion perception and social inference. Measures were also taken of executive
      function, working memory, information processing speed, verbal/non-verbal
      learning and psychological distress. FINDINGS: After adjusting for age, sex, pre
      morbid IQ and psychological distress, the MAIN group was impaired relative to CON
      (beta = -0.19, P < 0.05) and ABST (beta = -0.19, P < 0.05) on emotion perception
      and relative to CON (beta = -0.25, P < 0.001) and ABST (beta = -0.24, P < 0.01)
      on social inference. In neither case did the CON and ABST groups differ. For both
      emotion perception (P < 0.001) and social inference (P < 0.001), pre-morbid IQ
      was a significant independent predictor. Cognitive function was a major predictor
      of poor emotion perception (beta = -0.44, P < 0.001) and social inference (beta =
      -0.48, P < 0.001). Poor emotion recognition was also predicted by number of
      heroin overdoses (beta = -0.14, P < 0.05). Neither time in treatment or type of
      maintenance medication (methadone or buprenorphine) were related to performance.
      CONCLUSIONS: People in opioid maintenance treatment may have an impaired capacity
      for emotion perception and ability to make inferences about social situations.

PMID- 23164064
TI  - Treatment of two cases of Fournier's gangrene and review of the literature.
AB  - Fournier's gangrene is a rare polymicrobial necrotising soft tissue infection
      affecting the perineum and scrotum. It is rapidly progressive, destructive and
      associated with high morbidity and mortality. Management protocol includes prompt
      diagnosis, early institution of antibiotic therapy and adequate wound
      debridement, usually requiring multiple operations. Rapid accurate diagnosis is
      crucial for successful outcome, while early aggressive surgical intervention
      together with fluid, hemodynamic and nutritional support and broad-spectrum
      antibiotics are essential to reduce mortality. Dermatologists are often the first
      specialist consulted. Two cases of Fournier's gangrene are reported in this
      report. The aim of the report is to underline the importance of an immediate
      diagnostic approach to save patients, favoured by a close collaboration among
      dermatologist, surgeon and urologist. 

PMID- 23164065
TI  - Challenges of cardiopulmonary bypass-a review of the veterinary literature.
AB  - Cardiopulmonary bypass (CPB) has been used in veterinary medicine in experimental
      surgery and to address congenital and acquired diseases. We review the veterinary
      literature and expose common challenges of CPB in dogs and cats. Specifically, we
      describe the most specific elements of this technique in veterinary patients. The
      variety in animal size has made it difficult to standardize cannulation
      techniques, oxygenators, and priming volumes and solutions. The fact that one of
      the most common cardiovascular disorders, mitral valve disease, occurs
      predominantly in small dogs has limited the use of bypass in these patients
      because of the need for small, low prime oxygenators and pumps that have been
      unavailable until recently. Coagulation, hemostasis, and blood product
      availability have also represented important factors in the way CPB has developed
      over the years. The cost and the challenges in operating the bypass machine have
      represented substantial limitations in its broader use.

PMID- 23164066
TI  - Systematic review of clinical trials of small- and large-gel-particle hyaluronic
      acid injectable fillers for aesthetic soft tissue augmentation.
AB  - BACKGROUND: Hyaluronic acid (HA) is the most frequently injected filler for soft
      tissue augmentation in the United States. OBJECTIVE: To systematically review
      published evidence for aesthetic use of small- and large-gel-particle HA. METHODS
      AND MATERIALS: Clinical data on anatomic area, level of evidence, patient
      population, trial design, endpoints, efficacy, and safety were extracted from
      PubMed. RESULTS: Fifty-three primary clinical reports were analyzed. The highest
      quality efficacy evidence was for the nasolabial folds (NLFs), with 10
      randomized, blind, split-face, comparative trials. Several randomized, blind
      trials supported treatment of the glabella, lips, and hands. Lower-level evidence
      (from studies with nonrandomized, open-label, or retrospective designs) was
      recorded for the nasojugal folds (tear troughs), upper eyelids, nose,
      infraorbital hollows, oral commissures, marionette lines, perioral rhytides,
      temples, and cheeks. Common adverse events (AEs) across anatomic areas were pain,
      bruising, swelling, and redness. Serious AEs were uncommon (8 events in 8
      patients of 4,605 total patients) and were considered to be unrelated (7 events)
      or probably unrelated (1 event) to treatment. CONCLUSION: The efficacy and safety
      of small- and large-gel-particle HA are well established for NLFs; evidence for
      the glabella, lips, and hands is more limited. Preliminary reports in other
      anatomic regions suggest efficacy without major complications.

PMID- 23164067
TI  - Evaluation of photographs supporting an FFQ developed for adolescents.
AB  - OBJECTIVE: To evaluate the validity of food photographs used to support the
      reporting of food intake with an FFQ designed for adolescents from Rio de
      Janeiro, Brazil. DESIGN: A set of ninety-five food photographs was elaborated.
      The photographs' evaluation process included the acknowledgement of foods and
      portions in the pictures. In the identification of foods (ninety-five
      photographs) and typical portions (twelve photographs), the adolescents were
      requested to answer a structured questionnaire related to the food photographs.
      The identification of the portion size of amorphous foods (forty-three
      photographs) was performed using three different portion sizes of actual
      preparations. The proportions (and 95% confidence intervals) of adolescents who
      correctly identified foods and portion size in each photograph were estimated.
      SETTING: A public school in Niteroi, Rio de Janeiro State, Brazil. SUBJECTS:
      Sixty-two adolescents between 11.0 and 18.9 years old, randomly selected.
      RESULTS: At least 90% of adolescents correctly identified the food in ninety-two
      photographs and the food in the three remaining photographs was recognized by 80
      89% of the adolescents. At least 98% of the adolescents correctly identified
      eleven typical or natural portions in the food photographs. For amorphous foods,
      at least 70% of teenagers correctly identified the portion size in the photograph
      of thirty-one foods; for the other photographs, the portion size was correctly
      recognized by 50-69% of the adolescents for eight foods and by less than 50% of
      adolescents for four foods. CONCLUSIONS: The analysed photographs are appropriate
      visual aids to the reporting of food consumption by adolescents.

PMID- 23164068
TI  - Huvariome: a web server resource of whole genome next-generation sequencing
      allelic frequencies to aid in pathological candidate gene selection.
AB  - BACKGROUND: Next generation sequencing provides clinical research scientists
      with direct read out of innumerable variants, including personal, pathological
      and common benign variants. The aim of resequencing studies is to determine the
      candidate pathogenic variants from individual genomes, or from family-based or
      tumor/normal genome comparisons. Whilst the use of appropriate controls within
      the experimental design will minimize the number of false positive variations
      selected, this number can be reduced further with the use of high quality whole
      genome reference data to minimize false positives variants prior to candidate
      gene selection. In addition the use of platform related sequencing error models
      can help in the recovery of ambiguous genotypes from lower coverage data.
      DESCRIPTION: We have developed a whole genome database of human genetic
      variations, Huvariome, determined by whole genome deep sequencing data with high
      coverage and low error rates. The database was designed to be sequencing
      technology independent but is currently populated with 165 individual whole
      genomes consisting of small pedigrees and matched tumor/normal samples sequenced
      with the Complete Genomics sequencing platform. Common variants have been
      determined for a Benelux population cohort and represented as genotypes alongside
      the results of two sets of control data (73 of the 165 genomes), Huvariome Core
      which comprises 31 healthy individuals from the Benelux region, and Diversity
      Panel consisting of 46 healthy individuals representing 10 different populations
      and 21 samples in three Pedigrees. Users can query the database by gene or
      position via a web interface and the results are displayed as the frequency of
      the variations as detected in the datasets. We demonstrate that Huvariome can
      provide accurate reference allele frequencies to disambiguate sequencing
      inconsistencies produced in resequencing experiments. Huvariome has been used to
      support the selection of candidate cardiomyopathy related genes which have a
      homozygous genotype in the reference cohorts. This database allows the users to
      see which selected variants are common variants (> 5% minor allele frequency) in
      the Huvariome core samples, thus aiding in the selection of potentially
      pathogenic variants by filtering out common variants that are not listed in one
      of the other public genomic variation databases. The no-call rate and the
      accuracy of allele calling in Huvariome provides the user with the possibility of
      identifying platform dependent errors associated with specific regions of the
      human genome. CONCLUSION: Huvariome is a simple to use resource for validation of
      resequencing results obtained by NGS experiments. The high sequence coverage and
      low error rates provide scientists with the ability to remove false positive
      results from pedigree studies. Results are returned via a web interface that
      displays location-based genetic variation frequency, impact on protein function,
      association with known genetic variations and a quality score of the variation
      base derived from Huvariome Core and the Diversity Panel data. These results may
      be used to identify and prioritize rare variants that, for example, might be
      disease relevant. In testing the accuracy of the Huvariome database, alleles of a
      selection of ambiguously called coding single nucleotide variants were
      successfully predicted in all cases. Data protection of individuals is ensured by
      restricted access to patient derived genomes from the host institution which is
      relevant for future molecular diagnostics.

PMID- 23164069
TI  - Enucleation in Iceland 1992-2004: study in a defined population.
AB  - PURPOSE: To determine the incidence rate as well as causative diagnoses and
      surgical indications of enucleation in Iceland during the years 1992-2004.
      METHODS: A retrospective population-based incidence study involving the entire
      population of Iceland. Medical records of all patients who underwent enucleation
      in Iceland from January 1992 through December 2004 were reviewed. The annually
      updated Icelandic census was used as a denominator data. RESULTS: Fifty-six eyes
      were enucleated during 1992-2004. No eviscerations were done, and the three
      exenterations performed were not included in the study. The mean annual age
      adjusted incidence rate of enucleation in Iceland was 1.48 enucleations per 100
      000 population in comparison with 2.66 enucleations per 100 000 for the time
      period 1964-1991. With advancing age, a significant increasing linear trend
      existed (p < 0.001). The median age at enucleation was 51 years (SD 22; mean 55
      years; 16-91 years). The three most common surgical indications for enucleation
      were blind painful eye, suspected ocular malignancy and acute trauma. The most
      common causative diagnosis for enucleation was traumatic lesion (39%). The annual
      incidence was 2.00 enucleations per 100 000 for men and 0.95 for women. There
      were significantly more men in the traumatic lesion group (p < 0.001), but no
      gender predominance was found in the other groups of causative diagnoses (p =
      0.8). CONCLUSION: The overall mean annual incidence of enucleation in Iceland is
      continually decreasing, although the incidence of severe ocular trauma and ocular
      malignancy is fairly stable.

PMID- 23164070
TI  - Development of multiplex real-time PCR for simultaneous detection of three
      Potyviruses in tobacco plants.
AB  - AIMS: To develop a multiplex real-time PCR assay using TaqMan probes for the
      simultaneous detection and quantification of Tobacco etch virus (TEV), Potato
      virus Y (PVY) and Tobacco vein banding mosaic virus (TVBMV). METHODS AND RESULTS:
      Specific primer and probe combinations for TEV and TVBMV were developed from the
      coat protein region of the viral genome. To detect PVY, a primer and probe
      combination PVY-Univ F, PVY-Univ R and PVY-Univ P for amplifying the coat protein
      region of the virus genome was employed. The detection limit of multiplex real
      time PCR for these viruses was 10 copies MUl(-1) of the standard plasmid. The
      multiplex reaction was successful in the detection of these three pathogens, with
      no non-specific amplification and cross-reaction. CONCLUSIONS: This multiplex
      real-time PCR provides a rapid, effective, specific and sensitive method for the
      simultaneous detection and quantification of the three pathogens on infected
      tobacco plants. SIGNIFICANCE AND IMPACT OF THE STUDY: This multiplex real-time
      PCR will be useful not only for diagnostic, ecological, epidemiological and
      pathogenesis studies, but also for investigating host/virus or virus/virus
      interactions, in particular during mix infection.

PMID- 23164072
TI  - The dominance of the individual in intergroup relations research: understanding
      social change requires psychological theories of collective and structural
      phenomena.
AB  - Dixon et al. suggest that the psychological literature on intergroup relations
      should shift from theorizing "prejudice reduction" to "social change." A focus on
      social change exposes the importance of psychological theories involving
      collective phenomena like social norms and institutions. Individuals' attitudes
      and emotions may follow, rather than cause, changes in social norms and
      institutional arrangements.

PMID- 23164071
TI  - The structure of volcanic cristobalite in relation to its toxicity; relevance for
      the variable crystalline silica hazard.
AB  - BACKGROUND: Respirable crystalline silica (RCS) continues to pose a risk to human
      health worldwide. Its variable toxicity depends on inherent characteristics and
      external factors which influence surface chemistry. Significant population
      exposure to RCS occurs during volcanic eruptions, where ashfall may cover
      hundreds of square km and exposure may last years. Occupational exposure also
      occurs through mining of volcanic deposits. The primary source of RCS from
      volcanoes is through collapse and fragmentation of lava domes within which
      cristobalite is mass produced. After 30 years of research, it is still not clear
      if volcanic ash is a chronic respiratory health hazard. Toxicological assays have
      shown that cristobalite-rich ash is less toxic than expected. We investigate the
      reasons for this by determining the physicochemical/structural characteristics
      which may modify the pathogenicity of volcanic RCS. Four theories are considered:
      1) the reactivity of particle surfaces is reduced due to co-substitutions of Al
      and Na for Si in the cristobalite structure; 2) particles consist of aggregates
      of cristobalite and other phases, restricting the surface area of cristobalite
      available for reactions in the lung; 3) the cristobalite surface is occluded by
      an annealed rim; 4) dissolution of other volcanic particles affects the surfaces
      of RCS in the lung. METHODS: The composition of volcanic cristobalite crystals
      was quantified by electron microprobe and differences in composition assessed by
      Welch's two sample t-test. Sections of dome-rock and ash particles were imaged by
      scanning and transmission electron microscopy, and elemental compositions of rims
      determined by energy dispersive X-ray spectroscopy. RESULTS: Volcanic
      cristobalite contains up to 4 wt. % combined Al(2)O(3) and Na(2)O. Most
      cristobalite-bearing ash particles contain adhered materials such as feldspar and
      glass. No annealed rims were observed. CONCLUSIONS: The composition of volcanic
      cristobalite particles gives insight into previously-unconsidered inherent
      characteristics of silica mineralogy which may affect toxicity. The structural
      features identified may also influence the hazard of other environmentally and
      occupationally produced silica dusts. Current exposure regulations do not take
      into account the characteristics that might render the silica surface less
      harmful. Further research would facilitate refinement of the existing simple,
      mass-based silica standard by taking into account composition, allowing higher
      standards to be set in industries where the silica surface is modified.

PMID- 23164073
TI  - Prevalence of otomycosis in Khouzestan Province, south-west Iran.
AB  - BACKGROUND: This study aimed to investigate the prevalence of otomycosis and
      aetiological agents in Khouzestan province, south-west Iran. METHODS: This cross
      sectional study examined and cultured 881 swabs from suspected external otitis
      cases, collected from throughout Khouzestan province. Fungal agents were
      identified by slide culture and complementary tests when necessary. RESULTS: The
      mean patient age was 37 years. The 20-39 year age group had the highest
      prevalence of otomycosis: 293 cases, comprising 162 (55.3 per cent) women and 131
      (44.7 per cent) men. The seasonal distribution of cases was: summer, 44.7 per
      cent; autumn, 28.7 per cent; winter, 14.7 per cent; and spring, 11.9 per cent.
      The fungal agents isolated were Aspergillus niger (67.2 per cent), Aspergillus
      flavus (13 per cent), Candida albicans (11.6 per cent), Aspergillus fumigatus
      (6.2 per cent) and penicillium species (2 per cent). CONCLUSION: Fungal
      otomycosis is still one of the most important external ear diseases. In this
      study in south-west Iran, Aspergillus niger was the predominant aetiological
      agent. However, clinicians should be cautious of candidal otomycosis, which has a
      lower rate of incidence but is more prevalent among 20-39 year olds.

PMID- 23164076
TI  - Keeping the channels open: allogeneic endothelial cells modulate restenosis of
      injured blood vessels.

PMID- 23164077
TI  - Inner ear progenitor cells can be generated in vitro from human bone marrow
      mesenchymal stem cells.
AB  - AIM: Mouse mesenchymal stem cells (MSCs) can generate sensory neurons and produce
      inner ear hair cell-like cells. An equivalent source from humans is highly
      desirable, given their potential application in patient-specific regenerative
      therapies for deafness. In this study, we explored the ability of human MSCs
      (hMSCs) to differentiate into otic lineages. MATERIALS & METHODS: hMSCs were
      exposed to culture media conditioned by human fetal auditory stem cells. RESULTS:
      Conditioned media induced the expression of otic progenitor markers PAX8, PAX2,
      GATA3 and SOX2. After 4 weeks, cells coexpressed ATOH1, MYO7A and POU4F3
      (indicators of hair cell lineage) or neuronal markers NEUROG1, POU4F1 and NEFH.
      Inhibition of WNT signaling prevented differentiation into otic progenitors,
      while WNT activation partially phenocopied results seen with the conditioned
      media. CONCLUSION: This study demonstrates that hMSCs can be driven to express
      key genes found in the otic lineages and thereby promotes their status as
      candidates for regenerative therapies for deafness.

PMID- 23164078
TI  - Generation of inner ear sensory cells from bone marrow-derived human mesenchymal
      stem cells.
AB  - AIM: Hearing loss is the most common sensory disorder in humans, its main cause
      being the loss of cochlear hair cells. We studied the potential of human
      mesenchymal stem cells (hMSCs) to differentiate towards hair cells and auditory
      neurons. MATERIALS & METHODS: hMSCs were first differentiated to neural
      progenitors and subsequently to hair cell- or auditory neuron-like cells using in
      vitro culture methods. RESULTS: Differentiation of hMSCs to an intermediate
      neural progenitor stage was critical for obtaining inner ear sensory lineages.
      hMSCs generated hair cell-like cells only when neural progenitors derived from
      nonadherent hMSC cultures grown in serum-free medium were exposed to EGF and
      retinoic acid. Auditory neuron-like cells were obtained when treated with
      retinoic acid, and in the presence of defined growth factor combinations
      containing Sonic Hedgehog. CONCLUSION: The results show the potential of hMSCs to
      give rise to inner ear sensory cells.

PMID- 23164079
TI  - Host induction by transplanted neural stem cells in the spinal cord: further
      evidence for an adult spinal cord neurogenic niche.
AB  - AIM: To explore the hypothesis that grafts of exogenous stem cells in the spinal
      cord of athymic rats or rats with transgenic motor neuron disease can induce
      endogenous stem cells and initiate intrinsic repair mechanisms that can be
      exploited in amyotrophic lateral sclerosis therapeutics. MATERIALS & METHODS:
      Human neural stem cells (NSCs) were transplanted into the lower lumbar spinal
      cord of healthy rats or rats with transgenic motor neuron disease to explore
      whether signals related to stem cells can initiate intrinsic repair mechanisms in
      normal and amyotrophic lateral sclerosis subjects. Patterns of migration and
      differentiation of NSCs in the gray and white matter, with emphasis on the
      central canal region and ependymal cell-driven neurogenesis, were analyzed.
      RESULTS: Findings suggest that there is extensive cross-signaling between
      transplanted NSCs and a putative neurogenic niche in the ependyma of the lower
      lumbar cord. The formation of a neuronal cord from NSC-derived cells next to
      ependyma suggests that this structure may serve a mediating or auxiliary role for
      ependymal induction. CONCLUSION: These findings raise the possibility that NSCs
      may stimulate endogenous neurogenesis and initiate intrinsic repair mechanisms in
      the lower spinal cord.

PMID- 23164080
TI  - Functional motor recovery after peripheral nerve repair with an aligned nanofiber
      tubular conduit in a rat model.
AB  - AIM: Current synthetic tubular conduits are inferior to nerve autograft for the
      repair of segmental peripheral nerve injuries. We examined motor outcomes with
      the use of longitudinally aligned poly (L-lactide-co-caprolactone) nanofiber
      conduits for repair of nerve gap injury in a rat model. METHODS: Ten-millimeter
      segments of sciatic nerve were resected in 44 Lewis rats. The gaps were either
      left unrepaired (n = 6), repaired with nerve autograft (n = 19), or repaired with
      conduit (n = 19). After 12 weeks, nerve conduction latency, compound muscle
      action potential amplitude, muscle force and muscle mass were measured. The
      numbers of axons and axon diameters both within the grafts and distally were
      determined. RESULTS: After 12 weeks, gastrocnemius isometric tetanic force and
      muscle mass for the conduit group reached 85 and 82% of autograft values,
      respectively. Nerve conduction and compound muscle action potential were not
      significantly different between these two groups, although the latter approached
      significance. There was no recovery in the unrepaired group. CONCLUSION: Muscle
      recovery for the animals treated with this aligned nanofiber conduit approached
      that of autograft, suggesting the importance of internal conduit structure for
      nerve repair.

PMID- 23164081
TI  - Human tissue-engineered colon forms from postnatal progenitor cells: an in vivo
      murine model.
AB  - AIM: Loss of colon reservoir function after colectomy can adversely affect
      patient outcomes. In previous work, human fetal intestinal cells developed
      epithelium without mesenchyme following implantation in mice. However, for
      humans, postnatal tissue would be the preferred donor source. We generated tissue
      engineered colon (TEC) from postnatal human organoid units. MATERIALS & METHODS:
      Organoid units were prepared from human colon waste specimens, loaded onto
      biodegradable scaffolds and implanted into immunocompromised mice. After 4 weeks,
      human TEC was harvested. Immunofluorescence staining confirmed human origin,
      identified differentiated epithelial cell types and verified the presence of
      supporting mesenchyme. RESULTS: Human TEC demonstrated a simple columnar
      epithelium. Immunofluorescence staining demonstrated human origin and the three
      differentiated cell types of mature colon epithelium. Key mesenchymal components
      (smooth muscle, intestinal subepithelial myofibroblasts and ganglion cells) were
      seen. CONCLUSION: Colon can form from human progenitor cells on a scaffold in a
      mouse host. This proof-of-concept experiment is an important step in
      transitioning TEC to human therapy.

PMID- 23164082
TI  - Isolation and characterization of mesenchymal stem cell-like cells from healthy
      and inflamed gingival tissue: potential use for clinical therapy.
AB  - AIM: Postnatal mesenchymal stem cell (MSC)-like cells have previously been
      isolated and ex vivo-expanded from healthy gingival tissues. The aim of this
      research was to isolate and characterize MSC-like cells from inflamed gingival
      tissues and determine whether they retain the characteristics of MSC-like cells
      from healthy gingival tissues. MATERIALS & METHODS: Fifteen clonal lines of MSC
      like cells from three healthy gingival tissues (GMSC-H) and fifteen from three
      inflamed gingival tissues (GMSC-I) were generated. Bulk-cultured cell lines from
      healthy and inflamed gingival tissues were also established. In vitro and in vivo
      characterization studies of GMSC-Is were performed relative to GMSC-Hs. RESULTS:
      The incidence of clonogenic colony forming units-fibroblast was comparable
      between healthy and inflamed gingival tissues. GMSC-H and GMSC-I clones expressed
      MSC-associated markers CD44, CD73, CD90, CD105 and CD166. While the population
      doubling capacity of GMSC-Is was reduced compared with GMSC-Hs, both populations
      displayed a similar capacity to undergo osteogenic, adipogenic and chondrogenic
      differentiation in vitro. Following subcutaneous implantation in NOD/SCID mice,
      both GMSC-Hs and GMSC-Is formed dense connective tissue-like structures in vivo
      resembling natural gingival tissue. CONCLUSION: MSC-like populations exist within
      inflamed gingival tissue that are functionally equivalent to MSC-like cells
      derived from healthy gingival tissue. Given the relative abundance of inflamed
      gingival tissue and ease of accessibility, MSC-like cells from inflamed gingival
      tissues represent a newly identified population of postnatal stem cells with
      immense potential in tissue engineering applications.

PMID- 23164084
TI  - Cell sources for trachea tissue engineering: past, present and future.
AB  - Trachea tissue engineering has been one of the most promising approaches to
      providing a potential clinical application for the treatment of long-segment
      tracheal stenosis. The sources of the cells are particularly important as the
      primary factor for tissue engineering. The use of appropriate cells seeded onto
      scaffolds holds huge promise as a means of engineering the trachea. Furthermore,
      appropriate cells would accelerate the regeneration of the tissue even without
      scaffolds. Besides autologous mature cells, various stem cells, including bone
      marrow-derived mesenchymal stem cells, adipose tissue-derived stem cells,
      umbilical cord blood-derived mesenchymal stem cells, amniotic fluid stem cells,
      embryonic stem cells and induced pluripotent stem cells, have received extensive
      attention in the field of trachea tissue engineering. Therefore, this article
      reviews the progress on different cell sources for engineering tracheal cartilage
      and epithelium, which can lead to a better selection and strategy for engineering
      the trachea.

PMID- 23164085
TI  - Towards retinal ganglion cell regeneration.
AB  - Traumatic optic nerve injury and glaucoma are among the leading causes of
      incurable vision loss across the world. What is worse, neither pharmacological
      nor surgical interventions are significantly effective in reversing or halting
      the progression of vision loss. Advances in cell biology offer some hope for the
      victims of optic nerve damage and subsequent partial or complete visual loss.
      Retinal ganglion cells (RGCs) travel through the optic nerve and carry all visual
      signals to the brain. After injury, RGC axons usually fail to regrow and die,
      leading to irreversible loss of vision. Various kinds of cells and factors
      possess the ability to support the process of axon regeneration for RGCs. This
      article summarizes the latest advances in RGC regeneration.

PMID- 23164087
TI  - Novel heterocyclic analogues of firefly luciferin.
AB  - Five novel firefly luciferin analogues in which the benzothiazole ring system of
      the natural substrate was replaced with benzimidazole, benzofuran,
      benzothiophene, benzoxazole, and indole were synthesized. The fluorescence,
      bioluminescence, and kinetic properties of the compounds were evaluated with
      recombinant Photinus pyralis wild type luciferase. With the exception of indole,
      all of the substrates containing heterocycle substitutions produced readily
      measurable flashes of light with luciferase. Compared to that of luciferin, the
      intensities ranged from 0.3 to 4.4% in reactions with varying pH optima and times
      to reach maximal intensity. The heteroatom changes influenced both the
      fluorescence and bioluminescence emission spectra, which displayed maxima of 479
      528 and 518-574 nm, respectively. While there were some interesting trends in the
      spectroscopic and bioluminescence properties of this group of structurally
      similar substrate analogues, the most significant findings were associated with
      the benzothiophene-containing compound. This synthetic substrate produced slow
      decay glow kinetics that increased the total light-based specific activity of
      luciferase more than 4-fold versus the luciferin value. Moreover, over the pH
      range of 6.2-9.4, the emission maximum is 523 nm, an unusual 37 nm blue shift
      compared to that of the natural substrate. The extraordinary bioluminescence
      properties of the benzothiophene luciferin should translate into greater
      sensitivity for analyte detection in a wide variety of luciferase-based
      applications.

PMID- 23164088
TI  - The impact of stroke aphasia on health and well-being and appropriate nursing
      interventions: an exploration using the Theory of Human Scale Development.
AB  - AIMS AND OBJECTIVES: This paper considers the impact of aphasia on health and
      well-being and provides suggestions for appropriate nursing interventions.
      Background.  Effective communication is essential to holistic care and positive
      outcomes for individuals affected by aphasia. When verbal communication is
      absent, nurses fail to adequately use alternative strategies so that the standard
      of nurse/patient communication is frequently poor. DESIGN: This is a discursive
      paper which reviews relevant literature and uses the Theory of Human Scale
      Development as a framework for discussion. METHOD: The Theory of Human Scale
      Development is introduced. This theory emphasises that quality of life depends as
      much upon self-actualisation and relation building as on physical health. The
      theory is used within the discussion to highlight the significance of
      communication to quality of life and how its loss has profound psychological and
      social consequences. RESULTS: Aphasia results in 'loss of self'. The situation is
      exacerbated by inadequate healthcare communication strategies. Suggestions are
      offered regarding more appropriate strategies. Efficacy of family input is
      considered; nursing competence regarding language practice therapies is
      discussed, and the 'quest approach' is explored. Aphasia has a negative impact on
      relationships by denying access to support networks, which results in isolation.
      The individual's predicament is worsened by negative nursing responses. Positive
      nursing strategies, which alleviate effects of aphasia on individuals' social
      health, are investigated. Concept analysis and self-awareness exercises as
      methods of enhancing compassion skills are explored. The social model of
      disability is discussed to highlight the benefits to individuals of environmental
      adaptations. The social benefits of aphasia-group affiliation are discussed.
      CONCLUSION: The paper concludes by emphasising that fundamental human needs
      involve social and psychological as well as physical aspects. RELEVANCE TO
      CLINICAL PRACTICE: Nursing interventions must address all needs to provide
      holistic care in its fullest sense.

PMID- 23164083
TI  - Stem cell recruitment after injury: lessons for regenerative medicine.
AB  - Tissue repair and regeneration are thought to involve resident cell proliferation
      as well as the selective recruitment of circulating stem and progenitor cell
      populations through complex signaling cascades. Many of these recruited cells
      originate from the bone marrow, and specific subpopulations of bone marrow cells
      have been isolated and used to augment adult tissue regeneration in preclinical
      models. Clinical studies of cell-based therapies have reported mixed results,
      however, and a variety of approaches to enhance the regenerative capacity of stem
      cell therapies are being developed based on emerging insights into the mechanisms
      of progenitor cell biology and recruitment following injury. This article
      discusses the function and mechanisms of recruitment of important bone marrow
      derived stem and progenitor cell populations following injury, as well as the
      emerging therapeutic applications targeting these cells.

PMID- 23164089
TI  - Choice architecture as a means to change eating behaviour in self-service
      settings: a systematic review.
AB  - The primary objective of this review was to investigate the current evidence base
      for the use of choice architecture as a means to change eating behaviour in self
      service eating settings, hence potentially reduce calorie intake. Twelve
      databases were searched systematically for experimental studies with predefined
      choice architecture interventions in the period of June 2011-March 2012. The 12
      included studies were grouped according to type of interventions and underwent a
      narrative synthesis. The evidence indicates that (i) health labelling at point of
      purchase is associated with healthier food choice, while (ii) manipulating the
      plate and cutlery size has an inconclusive effect on consumption volume. Finally,
      (iii) assortment manipulation and (iv) payment option manipulation was associated
      with healthier food choices. The majority of studies were of very weak quality
      and future research should emphasize a real-life setting and compare their
      results with the effect of other more well-established interventions on food
      behaviour in self-service eating settings.

PMID- 23164090
TI  - Leave entitlements, time off work and the household financial impacts of
      quarantine compliance during an H1N1 outbreak.
AB  - BACKGROUND: The Australian state of Victoria, with 5.2 million residents,
      enforced home quarantine during a H1N1 pandemic in 2009. The strategy was
      targeted at school children. The objective of this study was to investigate the
      extent to which parents' access to paid sick leave or paid carer's leave was
      associated with (a) time taken off work to care for quarantined children, (b)
      household finances, and (c) compliance with quarantine recommendations. METHODS:
      We conducted an online and telephone survey of households recruited through 33
      schools (85% of eligible schools), received 314 responses (27%), and analysed the
      subsample of 133 households in which all resident parents were employed. RESULTS:
      In 52% of households, parents took time off work to care for quarantined
      children. Households in which no resident parent had access to leave appeared to
      be less likely to take time off work (42% vs 58%, p=0.08) although this
      difference had only borderline significance. Among parents who did take time off
      work, those in households without access to leave were more likely to lose pay
      (73% vs 21%, p<0.001). Of the 26 households in which a parent lost pay due to
      taking time off work, 42% experienced further financial consequences such as
      being unable to pay a bill. Access to leave did not predict compliance with
      quarantine recommendations. CONCLUSIONS: Future pandemic plans should consider
      the economic costs borne by households and options for compensating quarantined
      families for income losses.

PMID- 23164091
TI  - Tenosynoviotomy for sepsis of the digital flexor tendon sheath in 9 horses.
AB  - OBJECTIVE: To describe a tenosynoviotomy technique for treatment of sepsis of the
      digital flexor tendon sheath (DFTS) in horses and report long-term outcome. STUDY
      DESIGN: Case series. ANIMALS: Horses (n = 9). METHODS: Horses were positioned in
      lateral recumbency with the affected limb uppermost. A linear incision was made
      just lateral to the mesotenon beginning 5 cm proximal to the apices of the
      proximal sesamoid bones, extending 2 cm distal to the bifurcation of the
      superficial digital flexor tendon (SDFT). The incision was continued through the
      skin, subcutaneous tissue, palmar/plantar annular ligament, and DFTS. Tenotomy of
      the distal lateral branch of the SDFT was also performed. The site was thoroughly
      debrided, lavaged, and packed with gauze and allowed to heal by second intention.
      Follow-up was obtained via owner telephone interview. RESULTS: Mean surgery time
      was 32 minutes (range, 10-64 minutes). Systemic antibiotics were administered
      postoperatively (range, 11-46 days; mean, 23 days). Mean hospitalization was 11
      days (range, 0-49 days). Follow-up was available for 7 (70%) horses. One year
      postoperatively, 5 (71%) horses were serviceable for their intended use, and 2
      (29%) had been euthanatized. Of 5 survivors, 3 returned to ridden exercise, 1 was
      retired as a broodmare, and 1 was a broodmare. All owners were satisfied with the
      cosmetic appearance of the surgery site. CONCLUSION: Open drainage via
      tenosynoviotomy, performed as a salvage procedure, represents a feasible
      treatment for DFTS sepsis.

PMID- 23164092
TI  - CM-AVM syndrome in a neonate: case report and treatment with a novel flow
      reduction strategy.
AB  - Mutations in the RASA-1 gene underlie several related disorders of
      vasculogenesis. Capillary malformation-arteriovenous malformation (CM-AVM) is one
      such entity and was recently encountered in a neonate who demonstrated its
      clinical and radiologic features. A single mutation in the RASA-1 gene was
      detected.A novel flow reduction strategy was employed to a large AVM affecting
      the patient's upper limb. The imaging findings, surgical procedure and patient's
      improved post-operative state are described.

PMID- 23164093
TI  - Participation and service access rights for people with intellectual disability:
      a role for law?
AB  - BACKGROUND: Supported decision-making and personal budgets for services are the
      new paradigms. METHOD: Supported decision-making proposals from the Australian
      State of Victoria are analysed against international trends to determine the
      viability of laws reflecting new international norms of the United Nations
      Convention on the Rights of Persons with Disabilities 2006 (CRPD).
      RESULTS/CONCLUSIONS: The article concludes that it is desirable to pursue
      supported decision-making and allied legal reforms, but the contribution of the
      law is small and the new supported decision-making paradigms have similarities to
      old paternalist guardianship, as well as possible unintended consequences. It is
      suggested that realising the equality, support, protection, and socioeconomic
      service aspirations of the CRPD raise important practical challenges for
      governments, for service providers, for families, and-centrally-for people with
      intellectual disability (ID).This article examines the limited contribution law
      can make to this enterprise.

PMID- 23164094
TI  - From Denmark to Delhi: the multisectoral challenge of regulating trans fats in
      India.
AB  - OBJECTIVE: India has proposed legislating an upper limit of trans fat in
      partially hydrogenated vegetable oils and mandating trans fat labelling in an
      effort to reduce intakes. The objective of the present study was to examine the
      complexities of regulating trans fat in India by examining the policy processes
      involved and the perceived implementation challenges. DESIGN: Semi-structured
      interviews (n 18) were conducted with key informants from various sectors.
      Interviewees were asked about sources of trans fat in the food supply, existing
      policies that may influence trans fats and perceived challenges related to the
      proposed trans fat regulation, in addition to questions tailored to their area of
      expertise. Interview data were organised based on common themes. SETTING:
      Interviews were conducted in India. SUBJECTS: Interviewees were key informants
      from various sectors including agriculture, trade, industry and health. RESULTS:
      Several themes were identified related to the complexity of regulating trans fat
      in India. A lack of trans fat awareness, the large unorganised retail sector, a
      need for suitable alternative products that are both acceptable to consumers and
      affordable, and a need to build capacity were crucial factors affecting India's
      ability to successfully regulate trans fat. The limited number of food inspectors
      will create an additional challenge in terms of enforcement of trans fat
      regulation. CONCLUSIONS: Although India will face challenges in regulating trans
      fat, legislating an upper limit of trans fat in partially hydrogenated vegetable
      oils will likely be the most effective approach to reducing it in the food
      supply. Ongoing engagement with industry, agriculture, trade and processing
      sectors will prove essential in terms of product reformulation.

PMID- 23164095
TI  - The development and evaluation of the Australian child and adolescent recommended
      food score: a cross-sectional study.
AB  - BACKGROUND: Diet quality tools have been developed to assess the adequacy of
      dietary patterns for predicting future morbidity and mortality. This study
      describes the development and evaluation of a brief food-based diet quality index
      for use with children at the individual or population level. The Australian Child
      and Adolescent Recommended Food Score (ACARFS) was developed to reflect adherence
      to the Dietary Guidelines for Children and Adolescents in Australia and modelled
      on the approach of the US Recommended Food Score. METHODS: The ACARFS has eight
      sub-scales and is scored from zero to 73. The diet quality score was evaluated by
      assessing correlation (Spearman's correlations) and agreement (weighted kappa
      statistics) between ACARFS scores and nutrient intakes, derived from a food
      frequency questionnaire in 691 children (mean age 11.0, SD 1.1) in New South
      Wales, Australia. Nutrient intakes for ACARFS quartiles were compared with the
      relevant Australian nutrient reference values. RESULTS: ACARFS showed slight to
      substantial agreement (kappa 0.13-0.64) with nutrient intakes, with statistically
      significant moderate to strong positive correlations with all vitamins, minerals
      and energy intake (r = 0.42-0.70). ACARFS was not related to BMI.Participants who
      scored less than the median ACARFS were more likely to have sub-optimal intakes
      of fibre, folic acid and calcium. CONCLUSION: ACARFS demonstrated sufficient
      accuracy for use in future studies evaluating diet quality. Future research on
      its utility in targeting improvements in the nutritional quality of usual eating
      habits of children and adolescents is warranted.

PMID- 23164096
TI  - Contrast recognizability during brilliant blue G - and heavier-than-water
      brilliant blue G-assisted chromovitrectomy: a quantitative analysis.
AB  - PURPOSE: To evaluate the potential of heavier-than-water brilliant blue G (BBG
      D(2) 0) to stain the internal limiting membrane (ILM) during chromovitrectomy.
      METHODS: In a nonrandomized, prospective, clinical multicentre study, 71
      consecutive chromovitrectomy interventions in 71 patients were analysed. During
      routine 23-gauge vitrectomy, conventional 0.25 mg/ml BBG was employed in 21 and
      0.25 mg/ml BBG-D(2) 0 in 50 patients. All interventions were videotaped. Post
      operatively, video frames were viewed and dye performance assessed subjectively
      and objectively. Main outcome measure was the chromaticity difference between the
      stained ILM and the unstained underlying retina, measured by means of an
      objective and quantitative analysis method to describe colour contrast strengths
      as they are perceived by the human eye. RESULTS: Removal of the ILM was possible
      in all interventions without additional vital dyes. BBG-D(2) 0 readily sank to
      the retinal surface, while conventional BBG tended to swirl up throughout the
      vitreous cavity. Conventional BBG was removed either with active suction or with
      a flute needle. Brilliant blue G-D(2) 0 needed to be whirled up from the retinal
      surface with a flute needle before aspiration. Objective chromaticity
      measurements yielded a mean chromaticity score of 7.98 for BBG-D(2) 0 and 6.51
      for BBG (p = 0.09). CONCLUSIONS: Brilliant blue G-D(2) 0 readily sinks to the
      retinal surface after injection and can be conveniently removed with a flute
      needle or active suction during chromovitrectomy. Based on the premises of the
      chromaticity measurements in this study, BBG's ILM staining capacity was not
      significantly improved through the recent revision its preparation, although a
      tendency towards slightly improved contrasts between the ILM and the underlying
      retina was observed.

PMID- 23164098
TI  - Short-term laryngeal electromyography and histopathological findings after
      primary reconstruction of the inferior laryngeal nerve in rabbits: prospective
      study.
AB  - INTRODUCTION: The recurrent laryngeal nerve can be injured during surgery. This
      study investigated recurrent laryngeal nerve reinnervation. OBJECTIVE: To study
      the short-term effects of primary anastomosis of the recurrent laryngeal nerve,
      by laryngeal electromyography and histopathological analysis, in a rabbit model.
      METHOD: Twenty Zealand rabbits underwent either right recurrent laryngeal nerve
      (1) transection with excision of 1 cm or (2) transection and end-to-end primary
      anastomosis. Vocal fold movements, laryngeal electromyography results and
      histological changes were recorded. RESULTS: Vocal fold analysis showed a
      paramedian vocal fold in both groups, with perceptible vibratory movements in
      group two. Electromyography revealed total denervation potentials in group one,
      but denervation and regeneration signs in group two. Histopathologically,
      hyperkeratosis and parakeratosis of the vocal fold mucosa were seen in group one,
      and signs of parakeratosis and hyperplasia in group two. CONCLUSION: Even under
      ideal conditions for primary recurrent laryngeal nerve anastomosis, a return to
      normal muscle function is unlikely. However, such anastomosis prevents muscle
      atrophy, and should be performed as soon as possible. The degree of nerve
      recovery is associated with the number, amplitude and myelination level of
      fibrils returning to the original motor end-plaque.

PMID- 23164097
TI  - DISCOVER: Dutch Iliac Stent trial: COVERed balloon-expandable versus uncovered
      balloon-expandable stents in the common iliac artery: study protocol for a
      randomized controlled trial.
AB  - BACKGROUND: Iliac artery atherosclerotic disease may cause intermittent
      claudication and critical limb ischemia. It can lead to serious complications
      such as infection, amputation and even death. Revascularization relieves symptoms
      and prevents these complications. Historically, open surgical repair, in the form
      of endarterectomy or bypass, was used. Over the last decade, endovascular repair
      has become the first choice of treatment for iliac arterial occlusive disease. No
      definitive consensus has emerged about the best endovascular strategy and which
      type of stent, if any, to use. However, in more advanced disease, that is, long
      or multiple stenoses or occlusions, literature is most supportive of primary
      stenting with a balloon-expandable stent in the common iliac artery (Jongkind V
      et al., J Vasc Surg 52:1376-1383,2010). Recently, a PTFE-covered balloon
      expandable stent (Advanta V12, Atrium Medical Inc., Hudson, NH, USA) has been
      introduced for the iliac artery. Covering stents with PTFE has been shown to lead
      to less neo-intimal hyperplasia and this might lower restenosis rates (Dolmatch B
      et al. J Vasc Interv Radiol 18:527-534,2007, Marin ML et al. J Vasc Interv Radiol
      7:651-656,1996, Virmani R et al. J Vasc Interv Radiol 10:445-456,1999). However,
      only one RCT, of mediocre quality has been published on this stent in the common
      iliac artery (Mwipatayi BP et al. J Vasc Surg 54:1561-1570,2011, Bekken JA et al.
      J Vasc Surg 55:1545-1546,2012). Our hypothesis is that covered balloon-expandable
      stents lead to better results when compared to uncovered balloon-expandable
      stents. METHODS/DESIGN: This is a prospective, randomized, controlled, double
      blind, multi-center trial. The study population consists of human volunteers aged
      over 18 years, with symptomatic advanced atherosclerotic disease of the common
      iliac artery, defined as stenoses longer than 3 cm and occlusions. A total of 174
      patients will be included. The control group will undergo endovascular dilatation
      or revascularization of the common iliac artery, followed by placement of one or
      more uncovered balloon-expandable stents. The study group will undergo the same
      treatment, however one or more PTFE-covered balloon-expandable stents will be
      placed. When necessary, the aorta, external iliac artery, common femoral artery,
      superficial femoral artery and deep femoral artery will be treated, using the
      standard treatment. The primary endpoint is absence of binary restenosis rate.
      Secondary endpoints are reocclusion rate, target-lesion revascularization rate,
      clinical success, procedural success, hemodynamic success, major amputation rate,
      complication rate and mortality rate. Main study parameters are age, gender,
      relevant co-morbidity, and several patient, disease and procedure-related
      parameters. TRIAL REGISTRATION: Dutch Trial Register, NTR3381.

PMID- 23164099
TI  - [Malignant mixed tumors of the parotid gland: a review of the Department of
      Otolaryngology Medical University of Warsaw experience].
AB  - OBJECTIVES: Pleomorphic adenoma (PA), or benign mixed tumor, is the most common
      salivary gland neoplasm. One of the factors influencing the management strategy
      in parotid PA is the risk of malignant transformation of this tumor. The
      objective of this study was the clinical and pathological analysis of malignant
      mixed tumors treated surgically at the Department of Otolaryngology, Medical
      University of Warsaw. MATERIALS AND METHODS: Retrospectively analysed clinical
      material included 12 patients with malignant mixed tumors selected from the group
      of 423 patients who underwent surgical treatment for parotid pleomorphic adenoma
      at the Department of Otolaryngology, Medical University of Warsaw, between
      January 1988 and June 2010. There were 7 women and 5 men; age ranged from 39 to
      67 years, with a mean of 56 years. The following parameters were analysed:
      demographic data, symptoms and disease duration, results of diagnostic tests,
      intraoperative data, results of histopathological examination, and adjunctive
      therapy. Four patients with a follow-up shorter than 5 years were excluded from
      the analysis of treatment results. RESULTS: A group of 12 patients with malignant
      mixed tumours included 10 (83.3%) cases of a primary tumor and 2 (16.7%) cases of
      a recurrent tumor. In the complete study sample (n=423), patients with malignant
      mixed tumor comprised: 2.8% of all patients, 2.5% of patients with primary PA and
      5.1% of patients with recurrent PA. Patients with malignant mixed tumor were
      significantly older than patients with benign PA (an average patient age was 56.0
      and 43.2 years, respectively p<0.001). 83.3% (n=10) patients were older than 50
      years. An average disease duration was longer in patients with malignant tumors.
      Considering all data from preoperative patient assessment (medical history,
      physical examination, FNAB, imaging studies), a preliminary diagnosis of
      malignant disease was made in 6 (50%) patients. All patients were treated
      surgically and 10 also had radiation therapy. The group of patients (n=8),
      subjected to evaluation of treatment results, included three patients with non
      invasive carcinoma and five patients with invasive carcinoma. All patients with
      non-invasive carcinoma were free from disease symptoms during the follow-up of 9
      to 21 years after the treatment. Five-year survival was 80% (4 of 5 patients) in
      a group of patients with invasive carcinoma. The rate of death for the underlying
      disease was the same (80%). An overall 5-year survival in patients with malignant
      mixed tumor was 87.5%. CONCLUSIONS: 1. Malignant transformation of pleomorphic
      adenoma more frequently occurs in recurrent tumors and in older patients. 2.
      Uncharacteristic clinical picture of malignant mixed tumors allows to make an
      accurate initial diagnosis only in half of the patients. 3. Extracapsular cancer
      invasion is a vital prognostic factor. Overall 5-year survival for invasive and
      noninvasive carcinoma was 80 % and 100 % respectively.

PMID- 23164100
TI  - [Sialendoscopy in treatment of sialolithiasis--our own experience based on group
      of 95 patients].
AB  - OBJECTIVES: The introduction of minimally invasive surgical procedures has
      significantly reduced the rate of major salivary gland removal due to
      sialolithiasis. The aim of the analysis was to assess the effectiveness of
      sialoendoscopy and combined approach in most difficult cases. MATERIAL AND
      METHODS: prospective study, tertiary university centre (Department of
      Otorhinolaryngology, Head and Neck Surgery, Poznan), between XII 2008 and V 2012,
      207 sialendoscopies were performed in 197 patients. In this number 158 patients
      had obstructive pathology of salivary glands, 95 confirmed gland or duct
      sialolithiasis: parotid - 31 and submandibular - 64. RESULTS: In the group of
      submandibular lithaiasis in 40 cases (62.5%) stones were removed endoscopically.
      Double approach (sialendoscopy and incision of mucosa of the floor of the mouth
      with removal of the stone was performed in 21 cases (32.8%). Only in 3 cases
      removal of submandibular gland was necessary. In the group of parotid
      sialolithiasis in 17 cases (54%) endoscopy was the definite treatment, in 9
      litothrypsy (ESWL) were necessary and in 5 combined approach. This five patients
      who failed SE were treated by combined transcutaneous (open surgery) and
      endoscopic procedure. We observed no incidence of salivary fistula after the
      incision of the duct; there was also no stenosis of the natural ostium due to the
      insertion of a stent. CONCLUSIONS: Sialoendoscopy is method of choice with high
      rate of success and gland preservation in small and moderate stones. The combined
      approach is indicated for large stones, complications and where there is a
      contraindication to established minimally invasive procedures.

PMID- 23164101
TI  - [The role of carbocystein in the treatment of sinusitis].
AB  - Chronic sinusitis is one of the most common presenting complaints of all doctor
      visits in the United States and Europe, with more than 13% of people affected in
      any given year. This disease has a wide range of impact on communities. Patients
      with recurrent or chronic sinusitis report a deteriorative sense of general
      health and vitality, when compared to general population. In our Department we
      perform about 600 functional endoscopic sinus surgeries (FESS) per year. Chronic
      rhinosinusitis represents a spectrum of inflammatory and infectious processes
      concurrently affecting the nose and paranasal sinuses. Among chronic paranasal
      sinusitis one must single out paranasal sinusitis with and without polyps. In the
      paranasal sinusitis patomechanism the blockage of natural ostium plays one of the
      most important roles. The closure of sinus proper ventilation passages leads to
      the triggering of many pathological occurrences within mucous membrane of this
      region. The treatment of paranasal sinusitis is diversified and involves a
      surgical procedure as well as anti-inflammatory and antiallergic drugs
      (medications) and mucolytics. Its purpose is to clear the nose through the
      elimination of bacterial infection, liquidating and removal of lying discharge
      and the restoration of the proper muco-ciliary transportation, and through this
      the improvement of local condition and faster recovery. In this work the usage of
      carboxycysteine to treat paranasal sinus conditions has been presented.

PMID- 23164102
TI  - [Assessment of Tumor Necrosis Factor alpha gene expression profile in selected
      structures of middle ear in patients with tympanosclerosis].
AB  - AIM OF THE STUDY: Tympanosclerosis is a middle ear disease located in submucous
      membrane. It leads to the tympanic membrane and ear ossicles fixation which
      results in severe conductive hearing impairment. The etiology of tympanosclerosis
      remains unclear. Cytokines play very important role in development of
      tympanosclerosis. The research aimed to assess gene expression level of pro
      inflammatory cytokine TNF-alpha in selected structures of middle ear in patients
      with chronic otitis media with tympanosclerosis. METHODOLOGY: The research was
      performed on middle ear tissues with tympanosclerosis achieved from 30 patients
      operated on in the Otolaryngology Department of the Medical University of Gdansk.
      The control group was formed by tympanic membranes sampled from 17 corpses of
      patients who died suddenly. Advancement of tympanosclerotic changes were grouped
      based on Tos classification. The TNF-alpha gene expression level was measured by
      real time PCR with specific hydrolysed probes (TaqMan). The gene expression level
      for TNF-alpha was correlated with clinical classification of tympanosclerosis.
      RESULTS: The level of gene profile expression for TNF-alpha in selected
      structures of the middle ear with tympanosclerosis was statistically significant,
      higher in comparison with the control group. The highest level of expression was
      observed in group two which is relevant to more advanced tympanosclerosis.
      CONCLUSION: Tympanosclerosis is a result of constant inflammatory process and it
      is modulated by cytokines including TNF-alpha. The positive correlation between
      gene expression level of TNF-alpha and tympanosclerosis could in the future
      contribute to antiinflammatory, medical treatment of tympanosclerosis.

PMID- 23164103
TI  - [Treatment results of otosclerosis regarding different types of prosthesis].
AB  - Surgery is the most effective method of improving hearing in patients with
      otosclerosis. The level of improvement depends on the stage of the disease and
      the chosen surgical method. THE AIM OF THIS STUDY: is to present hearing results
      in patients treated surgically by means of different types of prostheses and
      methods of vestibule sealing. MATERIAL AND METHODS: 230 cases (160 men, 70 women)
      between the age of 21 and 64 (median 36 years) treated for the first time in the
      Department of Otolaryngology of Medical University in Gdansk underwent
      epidemiologic and clinical analysis. The researches took into account the level
      of hearing improvement based on the reduced air-bone reserve for frequencies 0.5,
      1.0, 2.0 i 4.0 kHz in groups with where prostheses type 1 and 2 were used.
      RESULTS: 230 stapedotomies were performed. In 110 patients prosthesis type 1 was
      used (PTFE) and in 120 type 2 (piston PTFE with platinum tape). Each vestibule
      was sealed with homogenic fat tissue or fibrin sponge. After 6 weeks from the
      operation the air-bone reserve was reduced by 5 to 30 dB, the reserve existed
      after one year from the operation in some patients. 35% of the patients presented
      with vertigo after the operation and 5% with tinnitus. CONCLUSIONS: Stapedotomy
      is a method of hearing improvement in patients with otosclerosis. Best results
      are achieved when prosthesis type 2 is used and homogenic fat tissue serves to
      seal the vestibule. Broad opening of the vestibule may be the cause for vertigo
      and lack of hearing improvement occurrence.

PMID- 23164104
TI  - [Polymorphism of metalloproteinases MMP-1 and MMP-2 in risk of laryngeal cancer].
AB  - INTRODUCTION: The laryngeal cancer is the most common malignancy of the head and
      neck squamous cell carcinoma. Recent studies have revealed the role of genetic
      variations in the risk for laryngeal cancer. Polymorphic genes of matrix
      metalloproteinases may affect an individual genetic predisposition to the
      occurrence and clinical implications of the disease. THE AIM OF THE PRESENT
      STUDY: was to evaluate the role of polymorphic variants of MMP-1 and MMP-2 genes
      in the development of laryngeal carcinoma. MATERIAL AND METHODS: DNA was
      extracted from 633 individuals including 261 patients with laryngeal carcinoma
      and 372 healthy volunteers. Genotyping was carried out using TaqMan((r)) SNP
      Genotyping Assays (Applied Biosystems, USA). The distribution of polymorphisms of
      metalloproteinases were analysed: -1607 1G/2G MMP-1 and -1306 C/T MMP-2 gene.
      RESULTS: The distribution of genotypes of -1607 1G/2G MMP-1 polymorphism was
      significantly different in controls vs patients (chi(2) 15.05, p<0.001). The 2G
      allele carriers of MMP-1 -1607 1G/2G polymorphism were at higher risk for
      laryngeal carcinoma development (p<0.001). In the present study, 2G/2G
      polymorphic variant was the independent factor of cancer development (p=0.0015).
      CONCLUSION: Presented data suggest an implication of MMP-1 polymorphisms in the
      laryngeal carcinoma susceptibility. The presence of the MMP-1 2G allele seemed to
      be associated with increased risk for the disease. In summary, the current study
      have provided the evidence that an individual's risk for carcinoma of larynx is
      modulated by genetic factors.

PMID- 23164105
TI  - [Intraoperative navigation system in endoscopic sinus surgery].
AB  - Intraoperative navigation systems have been developed to increase the safety and
      efficiency of endoscopic sinus surgery. The objective of this study was to
      compare the application and utilization of optical and electromagnetical
      navigation systems in our own experience during the endoscopic surgery. MATERIAL
      AND METHODS: An optical-based image guidance systems (MatrixPolar Navigation
      System, Xion, Germany; Karl Storz Surgical Cockpit Navigation Panel Unit, Karl
      Storz, Germany; Stryker Navigation CartII ENT, Stryker, USA) and electromagnetic
      (Fusion ENT Navigation System, Medtronic, USA; Fiagon, fiagon GmbH, Germany) was
      used to performed 40 sinonasal and skull base surgeries. We compared the
      precision and accuracy of both types of systems and additional time necessary for
      setting up the system and real operating room time. We also analysed the
      convenience of navigation according to possibilities of easy instruments
      manipulation and fluency of navigation process. RESULTS: The mean measured
      accurancy of anatomical localization at start of the surgery for optical systems
      was 1.62 +/- 0.4mm and for electromagnetic respectively 1.79 +/- 0.39 mm. The
      time to set up the optical system was longer than for electromagnetic one (12 vs
      5 minutes). Operating room time was increased for both systems, for optical to 22
      vs 8 minutes for electromagnetic one. Surgeon's working comfort during operation
      was better for electromagnetic systems and allowed for fluently movements with
      instruments. CONCLUSIONS: Intraoperative navigation systems assist the surgeon
      with anatomical localization during endoscopic sinus surgery and improve its
      safety and efficacy. The choice of optical or electromagnetic system should be
      compared of effective costs and surgeon's preferences.

PMID- 23164106
TI  - [Importance of donor site vascular imaging in free fibula flap reconstruction].
AB  - INTRODUCTION: Free fibula flap is widely used in head and neck reconstruction.
      Imaging studies of the donor site can reveal vascular abnormalities and therefore
      prevent acute leg ischemia. AIM: Evaluation of the role of donor site vascular
      imaging studies for free fibula flap planing. MATERIAL AND METHODS: Out of 35
      free flap reconstructions performed in Otolaryngology Head and Neck Surgery
      Department in Medical University in Lublin in 2011-2012, there were 10 fibula
      flaps. Each patient had preoperative lower leg subtraction angiography performed.
      RESULTS: Lower leg angiography revealed vascular abnormalities in two out of 10
      patients scheduled for free fibula flap transfer. One had dominant peroneal
      artery and second occlusion of anterior tibial artery. In both cases fibula was
      harvested from the other leg. CONCLUSIONS: Imaging studies reveal lower leg
      vascular abnormalities in 20% of cases thus facilitate surgical plans
      alternations and prevent serious complications in free fibula flap patients.

PMID- 23164107
TI  - [The use of MRI DWI-imaging in assessment of cholesteatoma recurrences after
      canal wall up technique].
AB  - INTRODUCTION: The use of closed technique in cholesteatoma treatment carries a
      significant risk of development of residual disease thus requires a second look
      operation in a proportion of patients. In those with no residual cholesteatoma
      the second surgery could be avoided. THE AIM OF THE STUDY: was to evaluate the
      use of non-echo planar HASTE diffusion-weighted MR imaging in the detection of
      cholesteatoma in patients after canal wall up surgery due to cholesteatoma.
      MATERIAL AND METHODS: We evaluate the results of half-Fourier-acquisition single
      shot turbo-spin-echo (HASTE) diffusion-weighted magnetic resonance imaging in 18
      patients after canal wall up surgery performed 6 to 20 months after primary
      surgery. 16 patients were operated in our center and 2 elsewhere. All the
      patients underwent second look surgery that verified the result of MRI scanning.
      RESULTS: MRI DWI detected 2 cholesteatomas in patients operated elsewhere and
      none in patients operated in our center. Four cholesteatomas were found during
      second look operations. Two false negatives were in 1 patient with cholesteatoma
      pearl of less than 2mm in diameter and in 1 patient with mural cholesteatoma.
      There were no false positive results. CONCLUSION: Non EPI MRI DWI can be used as
      a screening tool to detect residual or recurrent cholesteatoma and may substitute
      the need of second look surgery.

PMID- 23164108
TI  - [The involvement of RCAS1 in creating a suppressive tumor microenvironment in
      patients with pharyngeal squamous cell carcinoma].
AB  - INTRODUCTION: Tumor microenvironment makes up the stroma of the neoplasm and is
      the tissue that determines the growth and progression of the tumor and its
      ability to create metastases. THE AIM OF THE PRESENT STUDY: has been to evaluate
      the potential role of RCAS1 protein in creating the suppressive tumor
      microenvironment in pharyngeal squamous cell carcinomas. The immunoreactivity of
      RCAS1, CD3, CD25, CD68, CD69 and Foxp3 was assessed in the tissue samples of the
      tumor, in tumor microenvironment and in the reference samples of palatine tonsils
      in chronic inflammation. RESULTS: A statistically significantly higher RCAS1
      antigen immunoreactivity was identified in pharyngeal cancer samples than in the
      stromal samples, the presence of RCAS1 positive macrophages infiltrating the
      tumor and its stroma was also noticed. The statistically significantly higher
      RCAS1 antigen immunoreactivity level was identified in the pharyngeal cancer
      samples in patients with the presence of lymph node metastases in comparison to
      patients without metastases. The infiltration of CD68 positive cells
      (macrophages) was significantly higher in the stromal tissue samples than in
      cancer samples and it was in both, the tumor and the stroma, significantly higher
      in patients with the presence of lymph node metastases than in patients without
      metastases. Additionally the presence of CD3 positive TILs was noticed in the
      tissue of the tumor and in its stroma, the cells were activated, typified by CD69
      immunoreactivity which was higher than in the reference samples, and impaired
      cytotoxicity with low CD25 antigen immunoreactivity. This observation confirmed
      the presence of selective immune suppression within the tumor and the stroma.
      CONCLUSION: RCAS1, an active factor secreted by the tumor and present in its
      stroma may play an important role in the phenomenon of tumor escape from host
      immunological surveillance and in creating the immune tolerance for the tumor
      cells, as well as in the tumor microenvironment remodeling with creating its
      suppressive profile enabling the further tumor growth and metastases.

PMID- 23164110
TI  - Inequality is a relationship.
AB  - A view of inequality as a relationship between the advantaged and the
      disadvantaged has gained considerable currency in psychological research.
      However, the implications of this view for theories and interventions designed to
      reduce inequality remain largely unexplored. Drawing on the literature on close
      relationships, we identify several key features that a relational theory of
      social change should include.

PMID- 23164109
TI  - [The sonoelastography of major salivary glands in chosen pathological
      conditions].
AB  - INTRODUCTION: Sonoelastography is a novel technique useful in noninvasive
      assessment of tissue elasticity. This method was found to date to be useful in
      noninvasive differentiation of benign and malignant lesions of multiple organs:
      thyroid gland, liver, prostate and breast. Elastograms were scored upon
      conventional subjective color scale and the detailed stiffness values in kPa were
      collected. THE AIM OF THE STUDY: was to examine usefulness of sonoelastography in
      assessment of salivary glands lesions. Material and Methods the group consisted
      of 99 patients treated in Department of Otolaryngology. 52 patients after
      radiotherapy for head and neck cancer, 4 treated for inflammatory disease - 2
      Sjoegren syndrome, 2 acute sialoadenitis and 43 consecutive patients with parotid
      tumors. The control group constituted 54 healthy volunteers. RESULTS: the mean
      stiffness value in 10 malignant tumors was 146.6 kPa and 88.7 kPa in 33 benign,
      the mean stiffness value of glandular parenchyma after radiotherapy was 43.18 kPa
      and in inflammatory disease 63.66 kPa. Mean elasticity of reference glandular
      tissue was 24.23 kPa. CONCLUSIONS: sonoelastography is fast, repetitive,
      noninvasive and objective method and it is useful in assessment of salivary
      glands lesions.

PMID- 23164111
TI  - Acute bacterial meningitis during and after pregnancy.

PMID- 23164112
TI  - International comparisons of preterm birth: higher rates of late preterm birth
      are associated with lower rates of stillbirth and neonatal death.
AB  - OBJECTIVE: To examine international rates of preterm birth and potential
      associations with stillbirths and neonatal deaths at late preterm and term
      gestation. DESIGN: Ecological study. SETTING: Canada, USA and 26 countries in
      Europe. POPULATION: All deliveries in 2004. METHODS: Information on preterm birth
      (<37, 32-36, 28-31 and 24-27 weeks of gestation) and perinatal deaths was
      obtained for 28 countries. Data sources included files and publications from
      Statistics Canada, the EURO-PERISTAT project and the National Center for Health
      Statistics. Pearson correlation coefficients and random-intercept Poisson
      regression were used to examine the association between preterm birth rates and
      gestational age-specific stillbirth and neonatal death rates. Rate ratios with
      95% confidence intervals were estimated after adjustment for maternal age, parity
      and multiple births. MAIN OUTCOME MEASURES: Stillbirths and neonatal deaths >= 32
      and >= 37 weeks of gestation. RESULTS: International rates of preterm birth (<37
      weeks) ranged between 5.3 and 11.4 per 100 live births. Preterm birth rates at 32
      36 weeks were inversely associated with stillbirths at >= 32 weeks (adjusted rate
      ratio 0.94, 95% CI 0.92-0.96) and >= 37 weeks (adjusted rate ratio 0.88, 95% CI
      0.85-0.91) of gestation and inversely associated with neonatal deaths at >= 32
      weeks (adjusted rate ratio 0.88, 95% CI 0.85-0.91) and >= 37 weeks (adjusted rate
      ratio 0.82, 95% CI 0.78-0.86) of gestation. CONCLUSIONS: Countries with high
      rates of preterm birth at 32-36 weeks of gestation have lower stillbirth and
      neonatal death rates at and beyond 32 weeks of gestation. Contemporary rates of
      preterm birth are indicators of both perinatal health and obstetric care
      services.

PMID- 23164114
TI  - Predicting live birth outcomes after in vitro fertilisation.

PMID- 23164115
TI  - Danish studies suggesting low and moderate prenatal alcohol exposure has no
      adverse effects on children aged 5 years did not use appropriate or effective
      measures of executive functioning.

PMID- 23164116
TI  - The effect of different alcohol drinking patterns in early to mid-pregnancy.

PMID- 23164117
TI  - Low and moderate alcohol consumption during pregnancy: effects on social
      behaviour and propensity to develop substance abuse in later life.

PMID- 23164118
TI  - Another perspective on 'the effect of different alcohol drinking patterns in
      early to mid pregnancy on the child's intelligence, attention, and executive
      function'.

PMID- 23164119
TI  - Authors' response to: Different perspectives on the methodology of studying the
      potential effects of different alcohol drinking patterns in early pregnancy on
      the neuropsychological development of young children.

PMID- 23164120
TI  - Elective birth at 37 weeks of gestation versus standard care for women with an
      uncomplicated twin pregnancy at term: the Twins Timing of Birth Randomised Trial.

PMID- 23164122
TI  - Elective birth at 37 weeks of gestation versus standard care for women with an
      uncomplicated twin pregnancy at term: the Twins Timing of Birth Randomised Trial.

PMID- 23164123
TI  - Women's health--what's new worldwide.

PMID- 23164124
TI  - Editor's choice: female genital mutilation and another real world.

PMID- 23164125
TI  - Bridging the gap between neuroscientific and psychodynamic models in child and
      adolescent psychiatry.
AB  - This article provides a selective review of the neuroscience and child
      psychoanalytic literature, focusing on areas of significant overlap and
      emphasizing comprehensive theories in developmental neuroscience and child
      psychoanalysis with testable mechanisms of action. Topics include molecular
      biology and genetics findings relevant to psychotherapy research, neuroimaging
      findings relevant to psychotherapy, brain regions of interest for psychotherapy,
      neurobiologic changes caused by psychotherapy, use of neuroimaging to predict
      treatment outcome, and schemas as a bridging concept between psychodynamic and
      cognitive neuroscience models. The combined efforts of neuroscientists and
      psychodynamic clinicians and theorists are needed to unravel the mechanisms of
      human mental functioning.

PMID- 23164126
TI  - The contemporary psychodynamic developmental perspective.
AB  - Authors address the transformations taking place in the last 25 years in the
      theory and practice of developmental psychoanalysis. They emphasize the role of
      attachment theory in this process and its clinical applications to the work with
      children and families and the social systems supporting them. The article also
      describes and explores a move toward an integrative and systemic developmental
      psychodynamic approach and its relevance to today's practitioner.

PMID- 23164127
TI  - Treating childhood trauma.
AB  - This review begins with the question "What is childhood trauma?" Diagnosis is
      discussed next, and then the article focuses on treatment, using 3 basic
      principles-abreaction, context, and correction. Treatment modalities and
      complications are discussed, with case vignettes presented throughout to
      illustrate. Suggestions are provided for the psychiatrist to manage
      countertransference as trauma therapy proceeds.

PMID- 23164128
TI  - Psychodynamic psychotherapy as treatment for depression in adolescence.
AB  - This article presents a psychodynamic approach to understanding and treating
      adolescent depression, based largely on the manual for short-term psychoanalytic
      psychotherapy (STPP) for adolescents (11-17 years old) with moderate to severe
      depression, developed for the IMPACT Study from Great Britain. Although the
      authors make reference to longer-term psychodynamic treatments, the 28-session
      model (plus 7 sessions of parent/carer work) used in the IMPACT Study informs the
      psychodynamic approach presented herein. In the course of discussing the
      analytical framework for depression and the treatment, a single case study is
      presented throughout to graphically illustrate the clinical course and outcomes.

PMID- 23164129
TI  - Treatment of anxiety in children and adolescents: using child and adolescent
      anxiety psychodynamic psychotherapy.
AB  - This article presents information on child and adolescent psychodynamic
      psychotherapy (CAPP). Following a definition of anxiety, the authors present
      study outcomes of nonpsychodynamic treatment approaches, alone and in combination
      with psychopharmacologic treatment, then explore psychodynamic approaches. A
      detailed overview of psychodynamic psychotherapy is presented, along with 2 cases
      illustrating the use of CAPP in young patients with anxiety. Also presented are
      tables and boxes summarizing CAPP therapeutic processes and strategies as
      intervention for anxious youth.

PMID- 23164130
TI  - Eating disorders in adolescents: review of treatment studies that include
      psychodynamically informed therapy.
AB  - In clinical practice, psychodynamic approaches represent an important component
      of the treatment for young people with eating disorders (EDs), even though the
      research literature remains modest regarding the most effective treatment for
      children, adolescents, or adults with an ED. Although there are very few clinical
      research studies of individual or family psychodynamic treatments of EDs, there
      is some evidence for efficacy from clinical trials. This article reviews studies
      of psychodynamically informed therapies for the treatment of EDs and discusses
      how the findings, although limited, suggest that further research into
      psychodynamic treatments of EDs in youth is warranted.

PMID- 23164131
TI  - Psychodynamic approaches to medically ill children and their traumatically
      stressed parents.
AB  - This article describes the authors' clinical experience of integrating
      psychodynamic therapeutic approaches in the care of medically ill children and
      their families. A case report of a boy with severe, chronic liver disease
      requiring a double organ transplant is described as an illustration of how such
      approaches cannot only improve quality of life and functioning but may also be
      life saving. The authors describe original research investigating how parents'
      traumatic stress and related interference with children's emotional regulation
      can compromise their ability to make meaning of their experience, thus posing a
      risk for adherence to the prescribed medical regimen.

PMID- 23164132
TI  - A fresh look at psychodynamic approaches to psychopathology in children and
      adolescents.

PMID- 23164133
TI  - Multidimensional life-table analysis of the effect of child mortality on total
      fertility in India,  1992-93, 1998-99, 2005-06.
AB  - This paper presents a new method for estimating the effect of child mortality on
      the total fertility rate (TFR). The method is based on discrete-time survival
      models of parity progression that allow construction of a multivariate
      multidimensional life table of fertility with four dimensions: woman's age,
      parity, duration in parity, and number of previous child deaths. Additional socio
      economic variables are included in the set of predictor variables in the
      underlying survival models of parity progression. The life table yields a
      replacement rate, which measures the effect of one additional child death on the
      TFR. The method is illustrated by applying it to three Indian National Family
      Health Surveys. Major findings are that dead children are incompletely replaced,
      and that the replacement rate rises as the TFR falls, reflecting women's
      increasing ability to control their fertility.

PMID- 23164134
TI  - The overall impairment of core executive function components in patients with
      amnestic mild cognitive impairment: a cross-sectional study.
AB  - BACKGROUND: It remains unclear how executive function (EF) is affected in the
      stage of amnestic mild cognitive impairment (aMCI). Previous studies using
      different methods to assess EF in patients with aMCI have reached inconsistent
      conclusions. The aim of the study was to explore the characteristics of EF
      impairments in patients with aMCI. METHODS: We investigated three core components
      of EF (i.e., working memory, response inhibition and task switching) based on the
      theoretical model of EF proposed by Miyake et al. (2000) in 34 aMCI patients and
      36 healthy elderly controls using computerized tasks programmed with E-prime (the
      2-back task and the keep track task for working memory, the stop-signal task and
      the Stroop task for response inhibition and the more-odd shifting task for task
      switching). The overall EF and the three individual EF components were compared
      between groups. For EF components that were impaired, the extent of impairment
      was compared using a paired analysis. The aMCI group was further divided into EF
      intact and EF-deficit groups according to their performances on the EF tests in
      clinical neuropsychological assessments. We tested for group differences among
      the normal controls and the EF-intact and EF-deficit aMCI groups and paid special
      attention to the comparisons between the EF-intact aMCI group and the control
      group. RESULTS: Compared to the control group, overall EF was significantly
      impaired in patients with aMCI (Wilks' lambda=0.572,P<0.001). Four tasks (the 2
      back task, the keep track task, the stop-signal task and the more-odd shifting
      task) that tapped the three core components of EF displayed group differences
      that favored the normal controls. The results of the Stroop task revealed no
      differences in performance between the two groups. The EF-intact aMCI patients
      also exhibited significantly impaired capabilities in the four tasks compared to
      the normal controls. There were no significant differences in the extent of
      impairment between the four affected tasks in the aMCI group, suggesting that the
      three core EF components were impaired to the same extent. CONCLUSIONS: Both the
      overall EF and all of the core EF components in the Miyake model of EF (working
      memory, response inhibition and task switching) were significantly impaired in
      aMCI patients, regardless of whether they had shown obvious clinical executive
      dysfunction.

PMID- 23164135
TI  - Quantitative analysis of the intra- and inter-subject variability of the whole
      salivary proteome.
AB  - BACKGROUND AND OBJECTIVE: Interest in human saliva is increasing for disease
      specific biomarker discovery studies. However, protein composition of whole
      saliva can grossly vary with physiological and environmental factors over time
      and it comprises human as well as bacterial proteins. MATERIAL AND METHODS: We
      compared intra- and inter-subject variabilities using complementary gel-based
      (two-dimensional difference gel electrophoresis, 2-D DIGE) and gel-free (liquid
      chromatography tandem mass spectrometry, LC-MS/MS) proteomics profiling of
      saliva. Unstimulated whole saliva of four subjects was examined at three
      different time-points (08.00 h, 12.00 h and 17.00 h) and variability of the
      saliva proteome was analyzed on two successive days by LC-MS/MS. RESULTS: In the
      2-D DIGE experiment, the median coefficient of variation (CV) for intra-subject
      variability was significantly lower (CV of 0.39) than that for inter-subject
      variability (CV of 0.57; CV of technical replicates 0.17). LC-MS/MS data
      confirmed the significantly lower variation within subjects over time (CV of
      0.37) than the inter-subject variability (CV of 0.53; CV of technical replicates
      0.11), and that the inter-subject variability was not time-dependent. CONCLUSION:
      Both techniques revealed similar trends of variations on technical, intra- and
      inter-subject level but provided peptide and protein focused information and
      should thus be used as complementary approaches. The data presented indicate that
      2-D DIGE as well as LC-MS/MS approaches are suitable for biomarker screening in
      saliva.

PMID- 23164136
TI  - Large scale extraction of poly(3-hydroxybutyrate) from Ralstonia eutropha H16
      using sodium hypochlorite.
AB  - Isolation of polyhydroxyalkanoates (PHAs) from bacterial cell matter is a
      critical step in order to achieve a profitable production of the polymer.
      Therefore, an extraction method must lead to a high recovery of a pure product at
      low costs. This study presents a simplified method for large scale poly(3
      hydroxybutyrate), poly(3HB), extraction using sodium hypochlorite. Poly(3HB) was
      extracted from cells of Ralstonia eutropha H16 at almost 96% purity. At different
      extraction volumes, a maximum recovery rate of 91.32% was obtained. At the
      largest extraction volume of 50 L, poly(3HB) with an average purity of 93.32% +/-
      4.62% was extracted with a maximum recovery of 87.03% of the initial poly(3HB)
      content. This process is easy to handle and requires less efforts than previously
      described processes.

PMID- 23164137
TI  - Food cost and nutritional quality. In reaction to the paper by Katz and
      colleagues.

PMID- 23164138
TI  - Beyond prejudice to prejudices.
AB  - Different groups, because they are perceived to pose different threats, elicit
      different prejudices. Collective action by disadvantaged groups can amplify the
      perception of specific threats, with predictable and potentially
      counterproductive consequences. It is important to carefully consider the threat
      based psychology of prejudice(s) before implementing any strategy intended to
      promote positive social change.

PMID- 23164139
TI  - Role of Montgomery salivary stent placement during pharyngolaryngectomy, to
      prevent pharyngocutaneous fistula in high-risk patients.
AB  - OBJECTIVE: To evaluate the incidence of pharyngocutaneous fistula after
      pharyngolaryngectomy with and without a Montgomery salivary stent. DESIGN:
      Retrospective analysis of patients with factors that predispose to the
      development of pharyngocutaneous fistula (i.e. disease extending to the
      supraglottic region, base of the tongue or pyriform sinuses, and/or
      radiochemotherapy). SUBJECTS: Between 2002 and 2008, 85 pharyngolaryngectomies
      were performed in our clinic. Of these patients, 31 were at increased risk of
      fistula development, of whom 45 per cent developed fistulas post-operatively.
      This subgroup of 31 patients was compared with a second subgroup of 22 patients
      at high risk of fistula development, treated between 2009 and 2011 with
      pharyngolaryngectomy and with a Montgomery salivary stent placed in advance
      during closure of the neopharynx. RESULTS: Statistical analysis showed a
      significant reduction in the rate of fistula development, from 45 to 9 per cent
      (p < 0.01), with application of the salivary stent. CONCLUSION: These data
      confirm the preventive effect of a salivary stent placed during
      pharyngolaryngectomy, for patients at high risk of fistula development.

PMID- 23164140
TI  - Serum beta-carotene and the risk of sudden cardiac death in men: a population
      based follow-up study.
AB  - OBJECTIVES: To examine whether serum concentrations of carotenoids are related to
      the risk of sudden cardiac death (SCD) in middle-aged men. METHODS: The study
      population consisted of 1031 Finnish men aged 46-65 years of the Kuopio Ischemic
      Heart Disease Risk Factor (KIHD) cohort. Serum concentrations of carotenoids were
      measured by high-performance liquid chromatography. The hazard ratios (HR) of
      serum beta-carotene, lycopene and alpha-carotene were estimated by using the Cox
      proportional hazard model after adjusting for age and other potential confounding
      factors. RESULTS: During a median follow-up of 15.9 years a total of 59 incidents
      of SCD occurred. After controlling for age, systolic blood pressure, waist
      circumference, smoking, alcohol consumption, years of education, serum LDL
      cholesterol, serum hs-CRP, diabetes, prevalent coronary heart disease (CHD) and
      congestive heart failure (CHF), men in the lowest tertile of serum concentrations
      of beta-carotene had a 2-fold increased risk of SCD (HR=2.15, 95% CI: 1.02-4.51;
      p=0.044) as compared to those in the highest tertile. The risk of SCD was
      borderline significant for lycopene. In addition, low serum beta-carotene
      concentrations increased the risk of cardiovascular disease (CVD) and total
      mortality. Lycopene and alpha-carotene were not related to the risk of SCD.
      CONCLUSIONS: Our findings suggest that low serum beta-carotene concentrations may
      increase the risk of SCD in middle-aged Finnish men. Furthermore, low serum beta
      carotene concentrations may be related to the risk of CVD and total mortality.

PMID- 23164141
TI  - Surgical site infection prevention: a qualitative analysis of an individualized
      audit and feedback model.
AB  - BACKGROUND: Surgical site infection (SSI) adversely affects patient outcomes and
      health care costs, so prevention of SSI has garnered much attention worldwide.
      Surgical site infection is recognized as an important quality indicator of
      patient care and safety. The purpose of this study was to use qualitative
      research methods to evaluate staff perceptions of the utility and impact of
      individualized audit and feedback (AF) data on SSI-related process metrics for
      their individual practice, as well as on overall communication and teamwork as
      they relate to SSI prevention. STUDY DESIGN: This study was performed in a
      tertiary care center, based on patients treated in the colorectal and hepatic
      pancreatic-biliary surgical oncology services. Eighteen clinicians were
      interviewed. Analysis of interviews via comparative analysis techniques and
      coding strategies were used to identify themes. RESULTS: The most important
      finding of this study was that although nearly all participants believed that the
      individualized AF model was useful in effecting individual practice change as
      well as improving awareness and accountability around individual roles in
      preventing SSIs, it was not seen as a means to enable the multidisciplinary
      teamwork required for sustainable practice changes. Moreover, such teamwork
      requires a team leader. CONCLUSIONS: Provision of individualized AF data had a
      significant impact on promoting individual practice change. Despite this, we
      concluded that practice change is a shared responsibility, requiring a team
      leader. So, AF had little bearing on establishing a necessary multidisciplinary
      team approach to SSI prevention, to create more effective and sustainable
      practice change among an entire team.

PMID- 23164142
TI  - Comparative effectiveness of magnetic resonance imaging in breast cancer.

PMID- 23164143
TI  - Repeat head CT scan in blunt trauma patients.

PMID- 23164145
TI  - Behavioral interpretation of absence of Hawthorne effect for turnover times.

PMID- 23164147
TI  - Laparoscopic distal pancreatectomy: trends in surgical technique.

PMID- 23164149
TI  - Life, liberty, the pursuit of happiness, and the Patient Protection and
      Affordable Care Act.

PMID- 23164151
TI  - Developing novel evidence-based interventions to promote asthma action plan use:
      a cross-study synthesis of evidence from randomised controlled trials and
      qualitative studies.
AB  - BACKGROUND: Long-standing randomised controlled trial (RCT) evidence indicates
      that asthma action plans can improve patient outcomes. Internationally, however,
      these plans are seldom issued by professionals or used by patients/carers. To
      understand how the benefits of such plans might be realised clinically, we
      previously investigated barriers and facilitators to their implementation in a
      systematic review of relevant RCTs and synthesised qualitative studies exploring
      professional and patient/carer views. Our final step was to integrate these two
      separate studies. METHODS: First, a theoretical model of action plan
      implementation was proposed, derived from our synthesis of 19 qualitative
      studies, identifying elements which, if incorporated into future interventions,
      could promote their use. Second, 14 RCTs included in the quantitative synthesis
      were re-analysed to assess the extent to which these elements were present within
      their interventions (that is, 'strong', 'weak' or 'no' presence) and with what
      effect. Matrices charted each element's presence and strength, facilitating
      analysis of element presence and action plan implementation. RESULTS: Four
      elements (professional education, patient/carer education, (patient/carer and
      professional) partnership working and communication) were identified in our model
      as likely to promote asthma plan use. Thirteen interventions reporting increased
      action plan implementation contained all four elements, with two or more strongly
      present. One intervention reporting no effect on action plan implementation
      contained only weakly present elements. Intervention effectiveness was reported
      using a narrow range of criteria which did not fully reflect the four elements.
      For example, no study assessed whether jointly developed action plans increased
      use. Whilst important from the professional and patient/carer perspectives, the
      integral role of these elements in intervention delivery and their effect on
      study outcomes was under-acknowledged in these RCTs. CONCLUSIONS: Our novel
      approach provides an evidence-base for future action plan interventions. Such
      interventions need to ensure all elements in our implementation model
      (patient/carer and professional education to support development of effective
      partnership working and communication) are strongly present within them and a
      wider range of criteria better reflecting the realities of clinical practice and
      living with asthma are used to measure their effectiveness. We now intend to test
      such a complex intervention using a cluster trial design.

PMID- 23164152
TI  - Metal-mediated targeting in the body.
AB  - Metal ions are important for many biological processes and are steadily available
      in the human body. Metal concentrations can be extremely high in diseased areas
      of various pathological conditions. Some synthetic and natural drugs need to be
      activated by metal ions as prodrugs. In this review, we provide a few examples to
      illustrate how metal ions activate and mediate drug targeting in the body. This
      knowledge may be helpful for the development of more effective drugs and
      pharmaceutical formulations.

PMID- 23164153
TI  - Release of neurotransmitters from glia.
AB  - There is no question about the fact that astrocytes and other glial cells release
      neurotransmitters that activate receptors on neurons, glia and vascular cells,
      and that calcium is an important second messenger regulating the release. This
      occurs in cell culture, tissue slice and in vivo. Negative results from
      informative experiments designed to test the mechanism of calcium-dependent
      neurotransmitter release from astrocytes and the ensuing effects on synaptic
      transmission, have been cited as evidence calling into question whether
      astrocytes release neurotransmitters under normal circumstances with effects on
      synaptic transmission. The special feature section in this issue of Neuron Glia
      Biology addresses these issues and other aspects of neurotransmitter release from
      astrocytes in communicating with neurons and glial cells. Together these studies
      suggest that application of vocabulary and concepts developed for synaptic
      communication between neurons can lead to confusion and apparent paradoxes with
      respect to communication by extracellular signaling molecules released from glia
      in response to functional activity.

PMID- 23164154
TI  - Visual fatigue and discomfort after stereoscopic display viewing.
AB  - PURPOSE: Different types of stereoscopic video displays have recently been
      introduced. We measured and compared visual fatigue and visual discomfort induced
      by viewing two different stereoscopic displays that either used the pattern
      retarder-spatial domain technology with linearly polarized three-dimensional
      technology or the circularly polarized three-dimensional technology using shutter
      glasses. METHODS: During this observational cross-over study performed at two
      subsequent days, a video was watched by 30 subjects (age: 20-30 years). Half of
      the participants watched the screen with a pattern retard three-dimensional
      display at the first day and a shutter glasses three-dimensional display at the
      second day, and reverse. The study participants underwent a standardized
      interview on visual discomfort and fatigue, and a series of functional
      examinations prior to, and shortly after viewing the movie. Additionally, a
      subjective score for visual fatigue was given. RESULTS: Accommodative magnitude
      (right eye: p < 0.001; left eye: p = 0.01), accommodative facility (p = 0.008),
      near-point convergence break-up point (p = 0.007), near-point convergence recover
      point (p = 0.001), negative (p = 0.03) and positive (p = 0.001) relative
      accommodation were significantly smaller, and the visual fatigue score was
      significantly higher (1.65 +/- 1.18 versus 1.20 +/- 1.03; p = 0.02) after viewing
      the shutter glasses three-dimensional display than after viewing the pattern
      retard three-dimensional display. CONCLUSIONS: Stereoscopic viewing using pattern
      retard (polarized) three-dimensional displays as compared with stereoscopic
      viewing using shutter glasses three-dimensional displays resulted in
      significantly less visual fatigue as assessed subjectively, parallel to
      significantly better values of accommodation and convergence as measured
      objectively.

PMID- 23164155
TI  - Assessing risk of breast cancer in an ethnically South-East Asia population
      (results of a multiple ethnic groups study).
AB  - BACKGROUND: Gail and others developed a model (GAIL) using age-at-menarche, age
      at-birth of first live child, number of previous benign breast biopsy
      examinations, and number of first-degree-relatives with breast cancer as well as
      baseline age-specific breast cancer risks for predicting the 5-year risk of
      invasive breast cancer for Caucasian women. However, the validity of the model
      for projecting risk in South-East Asian women is uncertain. We evaluated GAIL and
      attempted to improve its performance for Singapore women of Chinese, Malay and
      Indian origins. METHODS: Data from the Singapore Breast Screening Programme
      (SBSP) are used. Motivated by lower breast cancer incidence in many Asian
      countries, we utilised race-specific invasive breast cancer and other cause
      mortality rates for Singapore women to produce GAIL-SBSP. By using risk factor
      information from a nested case-control study within SBSP, alternative models
      incorporating fewer then additional risk factors were determined. Their accuracy
      was assessed by comparing the expected cases (E) with the observed (O) by the
      ratio (E/O) and 95% confidence interval (CI) and the respective concordance
      statistics estimated. RESULTS: From 28,883 women, GAIL-SBSP predicted 241.83
      cases during the 5-year follow-up while 241 were reported (E/O=1.00, CI=0.88 to
      1.14). Except for women who had two or more first-degree-relatives with breast
      cancer, satisfactory prediction was present in almost all risk categories. This
      agreement was reflected in Chinese and Malay, but not in Indian women. We also
      found that a simplified model (S-GAIL-SBSP) including only age-at-menarche, age
      at-birth of first live child and number of first-degree-relatives performed
      similarly with associated concordance statistics of 0.5997. Taking account of
      body mass index and parity did not improve the calibration of S-GAIL-SBSP.
      CONCLUSIONS: GAIL can be refined by using national race-specific invasive breast
      cancer rates and mortality rates for causes other than breast cancer. A revised
      model containing only three variables (S-GAIL-SBSP) provides a simpler approach
      for projecting absolute risk of invasive breast cancer in South-East Asia women.
      Nevertheless its role in counseling the individual women regarding their risk of
      breast cancer remains problematical and needs to be validated in independent
      data.

PMID- 23164156
TI  - Intrahepatic mRNA levels of SOCS1 and SOCS3 are associated with cirrhosis but do
      not predict virological response to therapy in chronic hepatitis C.
AB  - BACKGROUND: Antiviral treatment of chronic hepatitis C is not invariably
      successful, costly and associated with serious side-effects, and therefore should
      be indicated only when the chances of benefitting patients exceed the potential
      risks. The suppressor of cytokine signalling (SOCS) family members have been
      suggested to affect the rate of virological response to therapy, but the
      published evidence is conflicting. METHODS: We measured the intrahepatic SOCS1,
      SOCS3 and SOCS7 mRNA levels in 107 chronic hepatitis C patients and assessed
      their clinical and histological correlates with the virological response to
      therapy and with some factors known for affecting treatment outcome. RESULTS: By
      multivariate analysis, SOCS1, SOCS3 and SOCS7 mRNA levels were not associated
      with rapid or sustained virological response. Similarly, no association was found
      between the levels of any intrahepatic SOCS mRNA and those of the homeostasis
      model assessment of insulin resistance. Conversely, SOCS1 (OR 2.185, 95% CI 1.223
      3.906, P=0.0083) and SOCS3 (OR 40.601, 95% CI 2.357-699.25, P=0.0108) mRNA level
      (but not SOCS7), together with age (OR 1.156, 95% CI 1.049-1.275, P=0.0036), were
      independently associated with cirrhosis. CONCLUSIONS: Intrahepatic SOCS1, SOCS3
      and SOCS7 mRNA levels do not predict virological response to therapy in chronic
      hepatitis C. The association between SOCS1, SOCS3 and cirrhosis warrants further
      study.

PMID- 23164157
TI  - The morphology of the digestive tract and respiratory organs of the holothurian
      Cladolabes schmeltzii (Holothuroidea, Dendrochirotida).
AB  - The microanatomy of the digestive and respiratory systems of the holothurian
      Cladolabes schmeltzii was studied. The digestive tube of C. schmeltzii is divided
      into seven parts. The pharynx, esophagus, and stomach are lined with cuticular
      immersed epithelium. In these regions, the epithelial cells are connected via
      desmosomes, septate junctions, and rivet-like structures. The presence of the
      cuticle and rivet-like structures suggests an ectodermal origin for these parts
      of the digestive tube. The luminal intestinal epithelium is formed by vesicular
      enterocytes, which have different structures in different intestinal regions.
      Moreover, the epithelium of the first descending part of the intestine contains
      the granular enterocytes. The respiratory system consists of paired respiratory
      trees lined by a luminal epithelium that is formed by cells of irregular shape.
      The apical surface of these epithelial cells has few lamellae. The cells are
      connected to each other through a system of intercellular junctions, consisting
      of both desmosomes and well-developed septate junctions. The coelomic epithelium
      of the intestine and the respiratory trees consists of peritoneal and
      myoepithelial cells.

PMID- 23164158
TI  - Aquaporin 1 (AQP1) expression in experimentally induced osteoarthritic knee
      menisci: an in vivo and in vitro study.
AB  - Osteoarthritis (OA) of the knee is a major problem in our society. The
      development of new treatment options for OA is limited, because the
      pathophysiological mechanisms are not clearly understood, especially on the
      molecular level. Aquaporin 1 (AQP1) is a specific protein channels for water
      transport; it is expressed in articular chondrocytes, human synovitis, in
      chondrocytes of patients with rheumatoid arthritis or OA and in chondrocyte-like
      cells of human intervertebral disc. The aim of this study was to investigate the
      expression of AQP1, through immunohistochemistry, immunocytochemistry and Western
      blot, in experimentally induced OA knee menisci. AQP1 was studied in vivo in knee
      OA menisci from 36 rats that underwent medial or lateral meniscectomy, and in
      vitro on fibrochondrocytes derived from knee OA menisci rats. OA in rats was
      experimentally induced and tested by histomorphometric analysis. Histological
      results demonstrated structural alterations in OA menisci accompanied by a very
      strong AQP1 immunohistochemical and immunocytochemical staining. The Western blot
      analysis confirmed a strong expression of AQP1 in OA fibrochondrocytes cells. The
      results of the present research suggest that an activation of AQP1, induced by
      the OA process, may represent an endogenous mechanism, which can be used to
      control the tissue degeneration within OA articular joints.

PMID- 23164159
TI  - Intravitreal injection of expansile perfluoropropane (c(3)f(8)) for the treatment
      of vitreomacular traction.
AB  - PURPOSE: To study the efficacy of a single intravitreal injection of expansile
      gas in releasing vitreomacular traction. DESIGN: Retrospective, interventional
      case series. METHODS: Fifteen eyes of 14 consecutive patients with symptomatic
      and persistent vitreomacular traction (>3 months' duration) on spectral-domain
      optical coherence tomography (SD OCT) received a single intravitreal injection of
      0.3 mL 100% perfluoropropane (C(3)F(8)) as an alternative to pars plana
      vitrectomy (PPV). Primary outcome was the number of eyes with complete
      vitreomacular traction release on OCT 1 month following treatment. Secondary
      outcomes included changes in visual acuity (VA), foveal contour, central foveal
      thickness, and maximal foveal thickness 1 month following treatment, and final
      VA. RESULTS: Mean age (+/- SD) was 72.1 +/- 12.6 years. Mean follow-up was 398.7
      +/- 174.4 days. Vitreomacular traction was idiopathic in 7 eyes and associated
      with diabetes in 6. One month following treatment, vitreomacular traction was
      released in 6 eyes (40%). Three further eyes (20%) had resolution of
      vitreomacular traction within 6 months, 4 (27%) underwent PPV, and 2 (13%)
      subsequently declined surgery. Foveal contour was restored in 7 eyes (47%). VA
      and central foveal thickness were similar 1 month following treatment, but
      maximal foveal thickness decreased by 65.8 MUm (P = .041). Mean final VA
      decreased 0.03 logMAR units from baseline (P = .536). Eyes with vitreomacular
      traction release within 1 month had less extensive vitreomacular traction (P =
      .037), low vitreous face reflectivity, and maximal foveal thickness <500 MUm (P =
      .004) pretreatment. There were no associated adverse events. CONCLUSIONS:
      Intravitreal C(3)F(8) injection could offer a minimally invasive alternative to
      PPV in patients with symptomatic and persistent vitreomacular traction. It
      appears particularly effective in eyes with less extensive vitreomacular traction
      and low vitreous face reflectivity on SD OCT. Further studies are warranted.

PMID- 23164160
TI  - In depth analysis of risk factors for coeliac disease amongst children under 18
      years old in the Gaza strip. A cross sectional study.
AB  - Coeliac disease is an important clinical disorder affecting the human
      gastrointestinal tract leading to multiple signs and symptoms in different body
      organs. This disease was the subject of a cross sectional descriptive-analytic
      study conducted in the Gaza Strip during 2010. Objectives were oriented to
      identify and verify several variables and attributes affecting the prognosis of
      coeliac disease in the patients. Ninety five children out of 113 patients were
      arranged into two groups according to age from 2 to 11 years and from 12 to 18
      years old. Results showed the poor interest of health professionals regarding
      coeliac disease in the Gaza Strip. The mean age of study population was 5.47
      years for males and 8.93 years for females. The lifestyle of coeliac patients was
      directly proportional with better nutritional indictors. Poor recognition of the
      emblem illustrating gluten in foods implicates effective health awareness or
      promotion. The more knowledgeable patients or mothers (P = 0.036) were the more
      compliant. The compliance to giving gluten free foods outside home was
      statistically significant (P = 0.037). Similarly, cautious approach when buying
      foods or detergents (P = 0.011). According to BMI 74.4%, 23.4% and 3.2% of all
      patients were normal, underweight and overweight respectively. Albumin blood
      level was normal in 32.6% and low in 67.4%. Meanwhile, blood calcium level was
      normal in 76.8%, low in 21.1% and high in 2.1% of all patients. CONCLUSION: The
      study showed that recreation and social activities for coeliac patients are
      substantially missing in the Gaza Strip. Moreover, the study proved that AEI is a
      reliable centre for care of coeliac disease patients and conducting relevant
      studies. RECOMMENDATION: There is a need for thorough and continuous community
      and institutional mobilization regarding coeliac disease in the Gaza Strip and in
      Palestine.

PMID- 23164161
TI  - Food cost and nutritional quality. Reply to: 'In reaction to the paper by Katz
      and colleagues'.

PMID- 23164163
TI  - Prejudice and personality: a role for positive-approach processes?
AB  - Individuals differ in their support for social change. We argue that examinations
      of inequality and change would benefit from consideration of underlying
      personality processes. New data suggest that Right-Wing Authoritarianism and
      Social Dominance Orientation, indicators of support for inequality, may be
      motivated by biologically driven personality processes, particularly those
      related to positive-approach motivation.

PMID- 23164162
TI  - Epigenetic contributions in the development of rheumatoid arthritis.
AB  - Rheumatoid arthritis (RA) is an autoimmune disease, characterized by chronic
      inflammation of the joints with severe pain and swelling, joint damage and
      disability, which leads to joint destruction and loss of function. Despite
      extensive research efforts, the underlying cause for RA is still unknown and
      current therapies are more or less effective in controlling symptoms but still
      fail to cure the disease. In recent years, epigenetic modifications were found to
      strongly contribute to the development of RA by affecting diverse aspects of the
      disease and modifying gene expression levels and behavior of several cell types,
      first and foremost joint resident synovial fibroblasts (SF). RASF are the most
      common cell type at the site of invasion. Owing to their aggressive,
      intrinsically activated phenotype, RASF are active contributors in joint damage.
      RASF are characterized by their ability to secrete cytokines, chemokines and
      joint-damaging enzymes. Furthermore, these cells are resistant to apoptosis,
      leading to hyperplasia of the synovium. In addition, RASF have invasive and
      migratory properties that could lead to spreading of the disease to unaffected
      joints. Epigenetic modifications, including DNA methylation and post
      translational histone modifications, such as histone (de)acetylation, histone
      methylation and histone sumoylation were identified as regulatory mechanisms in
      controlling aggressive cell activation in vitro and in disease outcome in animal
      models in vivo. In the last 5 years, the field of epigenetics in RA has
      impressively increased. In this review we consider the role of diverse epigenetic
      modifications in the development of RA, with a special focus on epigenetic
      modifications in RASF. 

PMID- 23164165
TI  - Influence of amino acid moiety accessibility on the chiral recognition of
      cyclodextrin-amino acid mixed selectors in enantioselective gas chromatography.
AB  - Original mixed selectors were synthesized by coupling a single L-valine diamide
      moiety on permethylated beta-cyclodextrin. The structures of the new selectors
      were designed to limit the interactions between the L-valine derivative and
      cyclodextrin by removing the amino acid moiety from the cyclodextrin cavity by
      means of an amide linkage on mono-6-amino permethylated beta-CD or the insertion
      of a carboxymethyl group. The accessibility of the amino acid group moiety was
      thus facilitated. The new mixed selectors exhibited better enantioselectivity
      than Chirasil-L-Val for half (selector based on mono-6-amino permethylated beta
      CD) or more (selector with the carboxymethyl group) of the 41 amino acid
      derivatives. Molecular modeling confirmed that these results could be attributed
      to an increase in the distance between the chiral center of the amino acid and
      the cyclodextrin cavity allowing better access of the amino acid moiety. These
      new mixed chiral selectors demonstrated a novel enantioselective capability with
      the successful separation of more than 90 racemic mixtures among the 105 chiral
      compounds tested. These mixed selectors exhibited enhanced enantioselectivity in
      comparison to binary selectors previously described with respect to both
      enantiomer resolution and the number of separated chiral compounds. Moreover, an
      improvement of the enantioseparation factors compared to the corresponding
      'parent phases' for the amino acid derivatives was observed in many cases. These
      mixed selectors should therefore be considered some of the most versatile
      selectors for chiral gas chromatography.

PMID- 23164164
TI  - Remission, continuation and incidence of eating disorders during early pregnancy:
      a validation study in a population-based birth cohort.
AB  - BACKGROUND: We internally validated previously published rates of remission,
      continuation and incidence of broadly defined eating disorders during pregnancy
      in the Norwegian Mother and Child Cohort (MoBa) at the Norwegian Institute of
      Public Health. METHOD: A total of 77 267 pregnant women enrolled at 17 weeks
      gestation between 2001 and 2009 were split into a training sample (n = 41 243)
      from the version 2 dataset and a validation sample (n = 36 024) from the version
      5 dataset who were not in the original study. Internal validation of original
      rate models involved fitting a calibration model to compare model parameters
      between the two samples and bootstrap estimates of bias in the entire version 5
      dataset. RESULTS: Remission, continuation and incidence estimates remained
      stable. Pre-pregnancy prevalence estimates in the validation sample were:
      anorexia nervosa (AN; 0.1%), bulimia nervosa (BN; 1.0%), binge eating disorder
      (BED; 3.3%) and eating disorder not otherwise specified-purging disorder (EDNOS
      P; 0.1%). In early pregnancy, estimates were: BN (0.2%), BED (4.8%) and EDNOS-P
      (<0.01%). Incident BN and EDNOS-P during pregnancy were rare. The highest rates
      were for full or partial remission for BN and EDNOS-P and continuation for BED.
      CONCLUSIONS: We validated previously estimated rates of remission, continuation
      and incidence of eating disorders during pregnancy. Eating disorders, especially
      BED, during pregnancy were relatively common, occurring in nearly one in every 20
      women. Pregnancy was a window of remission from BN but a window of vulnerability
      for BED. Training to detect eating disorders by obstetricians/gynecologists and
      interventions to enhance pregnancy and neonatal outcomes warrant attention.

PMID- 23164166
TI  - Boron-containing peptidomimetics--a novel class of selective anti-tubercular
      drugs.
AB  - Medical treatment for tuberculosis is complicated nowadays by the appearance of
      new multiresistant strains, and therefore, new antibiotics are in great need.
      Here, we report the synthesis and in vitro testing of a new class of highly
      selective antimicrobial boron-containing peptidomimetics with compounds
      exhibiting activity against Mycobacterium tuberculosis at <=5 MUg/mL. The new
      approach developed makes it possible to synthesize variously substituted beta
      aminoboronic acids and their derivatives with a high level of
      diastereoselectivity.

PMID- 23164167
TI  - Pulmonary haptoglobin (pHp) is part of the surfactant system in the human lung.
AB  - Since the existence of pHp was demonstrated, it has been shown that this molecule
      and its receptor CD163 are regulated by different stimuli. Furthermore, a
      comparably fast secretion of pHp was described as well as the immuno-stimulatory
      effects. The intention of this study was to elucidate the role of pHp in the
      human lungs further. Here we show, by means of confocal microscopy and immune
      electron-microscopy, a clear co-localization of pHp with surfactant protein-B in
      lamellar bodies of alveolar epithelial cells type II. These results are
      underlined by immunohistochemical stainings in differently fixed human lung
      tissues, which show pHp in vesicular and released form. The images of the
      released form resemble the intended position of surfactant in the human alveolus.
      pHp is secreted by Alveolar epithelial cells type II as previously shown.
      Moreover, pHp is co-localized with Surfactant protein-B. We conclude that the
      presented data shows that pHp is a native part of the surfactant system in the
      human lung. VIRTUAL SLIDES:
      http://www.diagnosticpathology.diagnomx.eu/vs/2563584738239912.

PMID- 23164168
TI  - Thank you but not goodbye.

PMID- 23164169
TI  - Trends in excess of weight, underweight and adiposity among Spanish children from
      2004 to 2010: the Cuenca Study.
AB  - OBJECTIVE: To examine the trends in BMI and adiposity among schoolchildren from
      Cuenca, Spain, during 2004-2010. DESIGN: Two methodologically comparable surveys
      were carried out in 2004 and 2010. SETTING: Primary schools in Cuenca, a province
      in the middle of Spain. SUBJECTS: All schoolchildren aged 8-11 years, belonging
      to 4th and 5th grades from twenty schools in the Province of Cuenca, were invited
      to participate in both cross-sectional studies. Weight, height and body fat
      percentage (BF%) from bioelectrical impedance were measured with standardized
      procedures. RESULTS: The study included 550 boys and 539 girls in 2004, and 569
      boys and 531 girls in 2010. In 2010, 8.1 % of children were underweight, 25.9 %
      overweight and 9.5 % obese. From 2004 to 2010, the prevalence of overweight rose
      from 21.6 % to 28.0 % (P = 0.004) and BF % increased from 22.6 % to 24.0 % (P =
      0.001) among boys. No change was observed in overweight and BF % in girls, or in
      underweight and obesity in either sex. In boys, most of the distribution of BMI
      and BF % shifted to the right; in contrast, among girls no substantial change was
      apparent in the distribution of BMI and BF %. CONCLUSIONS: From 2004 to 2010 the
      prevalence of overweight and adiposity has continued to increase among boys.
      However, the obesity epidemic may have levelled off in girls. Given that the
      prevalence of childhood excess weight is still very high, the current evidence
      based efforts to halt the obesity epidemic in Spain should be strengthened.

PMID- 23164170
TI  - Echoing the call to move "beyond prejudice" in search of intergroup equality.
AB  - We also critique the myopic focus on prejudice reduction, but we do not support
      the call for a reconceptualization of prejudice. Redefining key psychological
      constructs is unproductive. Also, we point to interpersonal dynamics in cross
      group interaction as a key mechanism in the prejudice reduction/collective action
      paradox and point to solutions involving intrapersonal/interpersonal processes,
      as well as broader structural intergroup relations.

PMID- 23164171
TI  - Expression of haematogenous and lymphogenous chemokine receptors and their
      ligands on uveal melanoma in association with liver metastasis.
AB  - PURPOSE: Chemokine receptors and their ligands are involved in a number of cell
      processes, including normal cell trafficking as well as metastasis in cancer.
      During metastasis, they are thought to play a role in determining cancer cell
      distribution and target organs. The aim of this study was to examine the
      expression of the chemokine receptors CXCR4, CCR7 and CCR10 as well as their
      respective chemokine ligands (CXCL12, CCL19, CCL27) in human uveal melanomas.
      METHODS: Seventy formalin-fixed paraffin-embedded uveal melanoma specimens from
      patients treated in 1996-1997 were examined using immunohistochemistry and
      evaluated using an immune reactive score (IRS). RESULTS: The chemokine receptors
      CXCR4, CCR7 and CCR10 were primarily expressed in the cytoplasm of uveal melanoma
      cells, with CXCR4 (average IRS 8.2) and CCR7 (average IRS 5.7) showing the
      strongest expression, respectively. The chemokine ligand CCL19 demonstrated a
      moderate expression (average IRS 5.3), whereas the expression of receptor CCR10
      (average IRS of 3.4), ligand CCL27 (average IRS 2.5) and ligand CXCL12 (average
      IRS 0.6) by uveal melanoma cells was low. A significant association between liver
      metastases and chemokine expression was found for CCR7 expression (p = 0.037)
      only. Comparison of liver metastasis and choroid uveal melanoma (35.3%, n = 12 of
      34) versus ciliary body involvement (72.7%, n = 8 of 11) was significant (p =
      0.030). CONCLUSION: Chemokine receptors are more strongly expressed on uveal
      melanoma cells than their ligands. Our results show new aspects of the metastatic
      process in uveal melanoma.

PMID- 23164172
TI  - Improved corner detection by ultrasonic testing using phase analysis.
AB  - In ultrasonic testing, corners are used for sensitivity calibration in the form
      of notches, for measuring the sound velocity in the material, and as known
      reference points during testing. A 90 degrees  corner will always reflect
      incoming waves in the opposite direction due to a double reflection and therefore
      give a strong echo. This article presents a method for separating the echo from a
      corner from other echoes and more accurately find the position of the corner. The
      method is based on analysing the phase of the reflected signal. The proposed
      method was tested on a steel calibration block and the width of the indication
      was reduced by up to 50% compared to the amplitude signal. This results in a more
      accurate positioning of the corner. Using the phase instead of the amplitude will
      also improve the reliability, since reflections other than from corners will
      disappear.

PMID- 23164173
TI  - Ultrasonic imaging of 3D displacement vectors using a simulated 2D array and
      beamsteering.
AB  - Most quasi-static ultrasound elastography methods image only the axial strain,
      derived from displacements measured in the direction of ultrasound propagation.
      In other directions, the beam lacks high resolution phase information and
      displacement estimation is therefore less precise. However, these estimates can
      be improved by steering the ultrasound beam through multiple angles and combining
      displacements measured along the different beam directions. Previously,
      beamsteering has only considered the 2D case to improve the lateral displacement
      estimates. In this paper, we extend this to 3D using a simulated 2D array to
      steer both laterally and elevationally in order to estimate the full 3D
      displacement vector over a volume. The method is tested on simulated and phantom
      data using a simulated 6-10MHz array, and the precision of displacement
      estimation is measured with and without beamsteering. In simulations, we found a
      statistically significant improvement in the precision of lateral and elevational
      displacement estimates: lateral precision 35.69MUm unsteered, 3.70MUm steered;
      elevational precision 38.67MUm unsteered, 3.64MUm steered. Similar results were
      found in the phantom data: lateral precision 26.51MUm unsteered, 5.78MUm steered;
      elevational precision 28.92MUm unsteered, 11.87MUm steered. We conclude that
      volumetric 3D beamsteering improves the precision of lateral and elevational
      displacement estimates.

PMID- 23164174
TI  - Fractionated radiosurgery for painful spinal metastases: DOSIS - a phase II
      trial.
AB  - BACKGROUND: One third of all cancer patients will develop bone metastases and the
      vertebral column is involved in approximately 70% of these patients. Conventional
      radiotherapy with of 1-10 fractions and total doses of 8-30 Gy is the current
      standard for painful vertebral metastases; however, the median pain response is
      short with 3-6 months and local tumor control is limited with these rather low
      irradiation doses. Recent advances in radiotherapy technology - intensity
      modulated radiotherapy for generation of highly conformal dose distributions and
      image-guidance for precise treatment delivery - have made dose-escalated
      radiosurgery of spinal metastases possible and early results of pain and local
      tumor control are promising. The current study will investigate efficacy and
      safety of radiosurgery for painful vertebral metastases and three characteristics
      will distinguish this study. 1) A prognostic score for overall survival will be
      used for selection of patients with longer life expectancy to allow for analysis
      of long-term efficacy and safety. 2) Fractionated radiosurgery will be performed
      with the number of treatment fractions adjusted to either good (10 fractions) or
      intermediate (5 fractions) life expectancy. Fractionation will allow inclusion of
      tumors immediately abutting the spinal cord due to higher biological effective
      doses at the tumor - spinal cord interface compared to single fraction treatment.
      3) Dose intensification will be performed in the involved parts of the vertebrae
      only, while uninvolved parts are treated with conventional doses using the
      simultaneous integrated boost concept. METHODS / DESIGN: It is the study
      hypothesis that hypo-fractionated image-guided radiosurgery significantly
      improves pain relief compared to historic data of conventionally fractionated
      radiotherapy. Primary endpoint is pain response 3 months after radiosurgery,
      which is defined as pain reduction of >= 2 points at the treated vertebral site
      on the 0 to 10 Visual Analogue Scale. 60 patients will be included into this two
      centre phase II trial. CONCLUSIONS: Results of this study will refine the methods
      of patient selection, target volume definition, treatment planning and delivery
      as well as quality assurance for radiosurgery. It is the intention of this study
      to form the basis for a future randomized controlled trial comparing conventional
      radiotherapy with fractionated radiosurgery for palliation of painful vertebral
      metastases. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01594892.

PMID- 23164175
TI  - Validation of an FFQ to assess short-term antioxidant intake against 30 d food
      records and plasma biomarkers.
AB  - OBJECTIVE: To validate a brief FFQ developed for capturing short-term antioxidant
      intake in a sample of US college students. DESIGN: A seventy-four-item
      antioxidant FFQ was developed based on major antioxidant sources in the American
      diet. The FFQ was validated against 30 d food records (FR) and plasma antioxidant
      concentrations. The reliability of the FFQ was evaluated by two FFQ administered
      at a 1-month interval. Settings University of Connecticut, CT, USA. SUBJECTS:
      Sixty healthy college students. RESULTS: Estimates of dietary antioxidants from
      the FFQ were moderately to highly correlated with those estimated from the 30 d
      FR (r = 0.29-0.80; P < 0.05) except for gamma-tocopherol and beta-cryptoxanthin.
      Total antioxidant capacity from diet only or from diet and supplements estimated
      by the 30 d FR and FFQ were highly correlated (r = 0.67 and 0.71, respectively; P
      < 0.0001). The FFQ categorized 91 % of participants into the same or adjacent
      tertiles of antioxidant intake as the 30 d FR. Most dietary carotenoids estimated
      from the FFQ were correlated with plasma levels (P < 0.05). Correlation
      coefficients for test-retest reliability ranged from 0.39 to 0.86. More than 94 %
      of the participants were classified in the same or adjacent tertiles between the
      two administrations of the FFQ. CONCLUSIONS: The brief FFQ demonstrated
      reasonable validity for capturing a comprehensive antioxidant intake profile.
      This FFQ is applicable in epidemiological or clinical studies to capture short
      term antioxidant intake or to simply document the variations of antioxidant
      intake in intervention trials. Cross-validation studies are warranted in other
      target populations.

PMID- 23164176
TI  - Identification, assessment and management of fetal compromise.
AB  - The main goals of fetal surveillance are to avoid fetal death and to recognize
      the fetus that will benefit from early intervention with resuscitation or
      delivery. Surveillance can occur in the antepartum or intrapartum period.
      Continuous fetal heart rate monitoring is the most common form of surveillance in
      the intrapartum period. Several techniques are used in the antepartum period,
      including nonstress test, biophysical profile, and contraction stress test.
      Multiple techniques are used once distress is noted in the fetus, with the
      ultimate resuscitation effort being delivery.

PMID- 23164178
TI  - Cellular biology of end organ injury and strategies for prevention of injury.
AB  - The interruption of placental blood flow induces circulatory responses to
      maintain cerebral, cardiac, and adrenal blood flow with reduced renal, hepatic,
      intestinal, and skin blood flow. If placental compromise is prolonged and/or
      severe, total circulatory failure is likely with cerebral hypoperfusion and
      resultant hypoxic ischemic cerebral injury with collateral renal, cardiac, and
      hepatic injury. Management strategies should be targeted at restoring cerebral
      perfusion and oxygen delivery and minimizing the extent of secondary injury.
      Specifically, the focus should include the judicious use of supplemental oxygen,
      avoidance of hypoglycemia and elevated temperature in the delivery room, and the
      early administration of therapeutic hypothermia to high-risk infants.

PMID- 23164177
TI  - Physiology of transition from intrauterine to extrauterine life.
AB  - The transition from fetus to newborn is the most complex adaptation that occurs
      in human experience. Lung adaptation requires coordinated clearance of fetal lung
      fluid, surfactant secretion, and onset of consistent breathing. The
      cardiovascular response requires striking changes in blood flow, pressures, and
      pulmonary vasodilation. Energy metabolism and thermoregulation must be quickly
      controlled. The primary mediators that prepare the fetus for birth and support
      the multiorgan transition are cortisol and catecholamine. Abnormalities in
      adaptation are frequently found following preterm birth or cesarean delivery at
      term, and many of these infants need delivery room resuscitation to assist in
      this transition.

PMID- 23164179
TI  - The role of oxygen in the delivery room.
AB  - As recently as the year 2000, 100% oxygen was recommended to begin resuscitation
      of depressed newborns in the delivery room. However, the most recent
      recommendations of the International Liaison Committee on Resuscitation counsel
      the prudent use of oxygen during resuscitation. In term and preterm infants,
      oxygen therapy should be guided by pulse oximetry that follows the interquartile
      range of preductal saturations of healthy term babies after vaginal birth at sea
      level. This article reviews the literature in this context, which supports the
      radical but judicious curtailment of the use of oxygen in resuscitation at birth.

PMID- 23164180
TI  - Delivery room management of meconium-stained infant.
AB  - This article discusses the historical background, epidemiology, and
      pathophysiology of meconium-stained amniotic fluid and provides current concepts
      in delivery room management of meconium-stained neonate including the current
      Neonatal Resuscitation Program guidelines.

PMID- 23164181
TI  - Chest compressions for bradycardia or asystole in neonates.
AB  - When effective ventilation fails to establish a heart rate of greater than 60
      bpm, cardiac compressions should be initiated to improve perfusion. The 2-thumb
      method is the most effective and least fatiguing technique. A ratio of 3
      compressions to 1 breath is recommended to provide adequate ventilation, the most
      common cause of newborn cardiovascular collapse. Interruptions in compressions
      should be limited to not diminishing the perfusion generated. Oxygen (100%) is
      recommended during compressions and can be reduced once adequate heart rate and
      oxygen saturation are achieved. Limited clinical data are available to form
      newborn cardiac compression recommendations.

PMID- 23164182
TI  - Medications in neonatal resuscitation: epinephrine and the search for better
      alternative strategies.
AB  - Epinephrine remains the primary vasopressor for neonatal resuscitation
      complicated by asystole or prolonged bradycardia not responsive to adequate
      ventilation and chest compressions. Epinephrine increases coronary perfusion
      pressure primarily through peripheral vasoconstriction. Current guidelines
      recommend intravenous epinephrine administration (0.01-0.03 mg/kg). Endotracheal
      epinephrine administration results in unpredictable absorption. High-dose
      intravenous epinephrine poses additional risks and does not result in better long
      term survival. Vasopressin has been considered an alternative to epinephrine in
      adults, but there is insufficient evidence to recommend its use in newborn
      infants. Future research will focus on the best sequence for epinephrine
      administration and chest compressions.

PMID- 23164183
TI  - Resuscitation of preterm infants: delivery room interventions and their effect on
      outcomes.
AB  - Despite advances in neonatal care, the rate of oxygen dependence at 36 weeks'
      postmenstrual age or bronchopulmonary dysplasia has not fallen. Neonatologists
      are increasingly careful to apply ventilation strategies that are gentle to the
      lung in the neonatal intensive care unit. However, there has not been the same
      emphasis applying gentle ventilation strategies immediately after birth. A lung
      protective strategy should start immediately after birth to establish a
      functional residual capacity, reduce volutrauma and atelectotrauma, facilitate
      gas exchange, and improve oxygenation during neonatal transition. This article
      discusses techniques and equipment recommended by international resuscitation
      guidelines during breathing assistance in the delivery room.

PMID- 23164184
TI  - Infants with prenatally diagnosed anomalies: special approaches to preparation
      and resuscitation.
AB  - When a fetal anomaly is suspected, a multidisciplinary approach to diagnosis,
      counseling, pregnancy management, surveillance, delivery planning, and neonatal
      care is critical to creating a comprehensive management plan. This article
      provides a basic framework for integrating prenatal diagnostic and maternal-fetal
      care considerations, delivery planning, special resuscitation needs, and
      immediate and later neonatal care and evaluation into developing a thoughtful
      management plan for infants with prenatally diagnosed complex anomalies including
      congenital heart disease, intrathoracic masses, fetal airway obstruction, neural
      tube defects, abdominal wall defects, and skeletal dysplasia.

PMID- 23164186
TI  - Neonatal stabilization and postresuscitation care.
AB  - Neonatal mortality is a major health care concern worldwide. Neonatal
      resuscitation alone does not address most causes of neonatal mortality;
      caregivers need to be trained in both neonatal resuscitation and stabilization.
      Neonatal stabilization requires caregivers to evaluate whether babies are at-risk
      or unwell, to decide what interventions are required, and to act on those
      decisions. Several programs address neonatal stabilization in a variety of levels
      of care in both well-resourced and limited health care environments. This article
      suggests a shift in clinical, educational, and implementation science from a
      focus on resuscitation to one on the resuscitation-stabilization continuum.

PMID- 23164185
TI  - Optimal timing for clamping the umbilical cord after birth.
AB  - This article provides a brief overview of pros and cons of clamping the cord too
      early (within seconds) after birth. It also highlights evolving data that suggest
      that delaying cord clamping for 30 to 60 seconds after birth is beneficial to the
      baby, with no measurable negative effects either the baby or the mother.

PMID- 23164187
TI  - Hypoxic-ischemic encephalopathy and novel strategies for neuroprotection.
AB  - This article covers the outcome of full-term infants with encephalopathy due to
      hypoxic-ischemia and pathophysiology of brain injury following hypoxic-ischemia.
      Clinical and imaging evidence for hypothermia for neuroprotection is presented.
      The outcome of infants with hypothermia for encephalopathy due to hypoxic
      ischemia from recent trials is summarized. Facts regarding the clinical
      application of cooling obtained from the randomized trials and knowledge gaps in
      hypothermic therapy are presented. The review concludes with the future of
      hypothermia for neuroprotection.

PMID- 23164188
TI  - The delivery room of the future: the fetal and neonatal resuscitation and
      transition suite.
AB  - Despite advances in the understanding of fetal and neonatal physiology and the
      technology to monitor and treat premature and full-term neonates, little has
      changed in resuscitation rooms. The authors' vision for the Fetal and Neonatal
      Resuscitation and Transition Suite of the future is marked by improvements in the
      amount of physical space, monitoring technologies, portable diagnostic and
      therapeutic technologies, communication systems, and capabilities and training of
      the resuscitation team. Human factors analysis will play an important role in the
      design and testing of the improvements for safe, effective, and efficient
      resuscitation of the newborn.

PMID- 23164190
TI  - The neonatal golden hour.

PMID- 23164189
TI  - The mathematics of morality for neonatal resuscitation.
AB  - This article discusses the ethical issues surrounding the resuscitation of
      infants who are at great risk to die or survive with significant morbidity. Data
      are introduced regarding money, outcomes, and prediction. Gestational age
      influences some of the outcomes after birth more than others do. Prediction is
      possible at four stages of the resuscitation process. Data suggest that antenatal
      and delivery room predictions are inadequate, and prediction at the time of
      discharge is too late. The predictive value (>95%) for the outcome of death or
      survival with neurodevelopmental impairment is discussed.

PMID- 23164191
TI  - Resuscitation of the fetus and newborn.

PMID- 23164192
TI  - Role of surface charge on boundary slip in fluid flow.
AB  - For a smooth hydrophobic surface, slip occurs during fluid flow close to the
      boundary, known as boundary slip which can reduce fluid drag. The surface charge
      present at the interface is believed to affect the boundary slip. In this paper,
      the effect of surface charge on the fluid flow on a hydrophobic surface is
      studied in both deionized (DI) water and saline. Positive and negative voltages
      are applied to the substrate to vary the surface charge density. The
      electrostatic force and slip lengths are measured with different applied electric
      field. Results are the subject of the paper.

PMID- 23164193
TI  - Thermodynamically controllable transition from 3D to 2D self-assembly of a
      hydrogelator induced by the phase behavior of triblock copolymers.
AB  - Triblock copolymer PE6200 (PEO(10.5)-PPO(30)-PEO(10.5)) in aqueous solution can
      undergo a transition from an isotropic micellar phase to an anisotropic lamellar
      phase at a specific temperature. Based on this feature, the self-assembly
      behavior of a benzenetetracarboxylic acid based hydrogelator in aqueous solutions
      of PE6200 has been investigated. The results of small angle X-ray scattering
      (SAXS) measurements indicated that the hydrogelator self-assembled into stable
      three-dimensional network structures below 50  degrees C. In the range of 50-60 
      degrees C, a transition from three-dimensional to two-dimensional self-assembly
      was observed, which can be attributed to the fact that PE6200 undergoes a
      transition from an isotropic micellar phase to an anisotropic lamellar phase.
      Differential scanning calorimetry (DSC) and varying temperature laser Raman
      spectroscopy further confirmed the thermodynamically controllable transition of
      3D to 2D self-assembly. Controlling the self-assembly by utilizing the phase
      behavior of triblock copolymers is a novel strategy.

PMID- 23164194
TI  - Beyond prejudice: are negative evaluations the problem and is getting us to like
      one another more the solution?
AB  - For most of the history of prejudice research, negativity has been treated as its
      emotional and cognitive signature, a conception that continues to dominate work
      on the topic. By this definition, prejudice occurs when we dislike or derogate
      members of other groups. Recent research, however, has highlighted the need for a
      more nuanced and "inclusive" (Eagly 2004) perspective on the role of intergroup
      emotions and beliefs in sustaining discrimination. On the one hand, several
      independent lines of research have shown that unequal intergroup relations are
      often marked by attitudinal complexity, with positive responses such as affection
      and admiration mingling with negative responses such as contempt and resentment.
      Simple antipathy is the exception rather than the rule. On the other hand, there
      is mounting evidence that nurturing bonds of affection between the advantaged and
      the disadvantaged sometimes entrenches rather than disrupts wider patterns of
      discrimination. Notably, prejudice reduction interventions may have ironic
      effects on the political attitudes of the historically disadvantaged, decreasing
      their perceptions of injustice and willingness to engage in collective action to
      transform social inequalities. These developments raise a number of important
      questions. Has the time come to challenge the assumption that negative
      evaluations are inevitably the cognitive and affective hallmarks of
      discrimination? Is the orthodox concept of prejudice in danger of side-tracking,
      if not obstructing, progress towards social justice in a fuller sense? What are
      the prospects for reconciling a prejudice reduction model of change, designed to
      get people to like one another more, with a collective action model of change,
      designed to ignite struggles to achieve intergroup equality?

PMID- 23164195
TI  - Clustering gene expression data using a diffraction-inspired framework.
AB  - BACKGROUND: The recent developments in microarray technology has allowed for the
      simultaneous measurement of gene expression levels. The large amount of captured
      data challenges conventional statistical tools for analysing and finding inherent
      correlations between genes and samples. The unsupervised clustering approach is
      often used, resulting in the development of a wide variety of algorithms. Typical
      clustering algorithms require selecting certain parameters to operate, for
      instance the number of expected clusters, as well as defining a similarity
      measure to quantify the distance between data points. The diffraction-based
      clustering algorithm however is designed to overcome this necessity for user
      defined parameters, as it is able to automatically search the data for any
      underlying structure. METHODS: The diffraction-based clustering algorithm
      presented in this paper is tested using five well-known expression datasets
      pertaining to cancerous tissue samples. The clustering results are then compared
      to those results obtained from conventional algorithms such as the k-means, fuzzy
      c-means, self-organising map, hierarchical clustering algorithm, Gaussian mixture
      model and density-based spatial clustering of applications with noise (DBSCAN).
      The performance of each algorithm is measured using an average external criterion
      and an average validity index. RESULTS: The diffraction-based clustering
      algorithm is shown to be independent of the number of clusters as the algorithm
      searches the feature space and requires no form of parameter selection. The
      results show that the diffraction-based clustering algorithm performs
      significantly better on the real biological datasets compared to the other
      existing algorithms. CONCLUSION: The results of the diffraction-based clustering
      algorithm presented in this paper suggest that the method can provide researchers
      with a new tool for successfully analysing microarray data.

PMID- 23164196
TI  - Outcomes of heart failure-related hospitalization in adults with congenital heart
      disease in the United States.
AB  - BACKGROUND: Heart failure (HF) accounts for >3 million hospital admissions
      annually in adults with acquired cardiovascular disease, but there are limited
      data on HF admissions in adults with congenital heart disease (ACHD). The purpose
      of this study was to test the hypotheses that HF admissions are common in ACHD
      and associated with significant morbidity and mortality. METHODS: The 2007
      Nationwide Inpatient Sample was used to assess national prevalence, morbidities,
      and risk factors for mortality during hospitalizations among ACHD with HF.
      RESULTS: Of the 84,308 (95% CI 71,345-97,272) ACHD admissions in the United
      States in 2007, 17,193 (95% CI 14,157-20,229) had a diagnosis of HF (20%). ACHD
      with HF was associated with an increased risk of death compared to ACHD without
      HF (OR 3.3, 95% CI 2.6-4.1). On multivariable analysis independent risk factors
      for mortality included nonoperative intubation (OR 6.1, 95% CI 3.3-11.4), sepsis
      (OR 4.3, 95% CI 2.4-7.4), and acute myocardial infarction (OR 3.2, 95% CI 1.8
      5.7). Cardiac defects associated with an increased risk of mortality included
      ventricular septal defects (VSDs) (OR 1.8, 95% CI 1.0-3.4). CONCLUSIONS: In this
      large population-based study, HF-related hospitalizations were common in ACHD and
      associated with an increased risk of death compared to non-HF admissions. The
      risk of mortality is increased with the diagnoses of VSDs and the presence of
      specific comorbidities such as respiratory failure and sepsis.

PMID- 23164198
TI  - Tick infestations in extensively grazed cattle and efficacy trial of high-cis
      cypermethrin pour-on preparation for control of ticks in Mvomero district in
      Tanzania.
AB  - BACKGROUND: This study aimed at determining the extent of tick infestations in
      extensively grazed cattle and assess the efficacy of Ecotix(r) acaricide (2.5%
      high cis cypermethrin) in Mvomero district in Tanzania. A total of 1200 Tanzanian
      short horn Zebu (TSHZ) from two farms in two villages were qualitatively assessed
      for tick infestations and 40 animals (grouped in 10s from each farm) were
      separated in their herds and quantitatively examined to establish the tick load.
      The animals were grouped in treatment regime groups (TxRG 1, 2, 3, and 4), TxRG 1
      being the control group was treated with water. Ecotix(r) was applied on day 0
      for TxRG 2, days 0 and 7 for TxRG 3 and days 0, 7 and 14 for TxRG 4 and tick load
      was monitored for 28 days. RESULTS: All the animals examined were infested with
      ticks. The identified ticks were Rhipicephalus appendiculatus (55%), Amblyomma
      variegatum (18%), R. (Boophilus) microplus (12.9%), R. (B) decoloratus (7.1%), R.
      evertsi evertsi (4.4%) and R. composites (2.6%). The overall mean (mean+/-SEM)
      tick density on day zero was 63+/-30 ticks per animal (ranging from 20-160). The
      mean tick density on day zero was 44.6+/-25.4, 74.6+/-30.3, 55.0+/-26.2 and 77+/
      33.5 for groups one, two, three and four respectively. Post-treatment
      quantitative assessment of tick burden revealed that the TxRG 1 animals
      maintained a tick load throughout the study period. A significant decrease in
      tick load in animals in groups TxRG 2, 3 and 4 (P=0.0001) with increasing
      frequency of Ecotix(r) application was recorded. There was however no significant
      difference in tick reduction between TxRG 3 and 4 (P=0.0986). Thus TxRG 3 would
      be sufficient for the monthly tick treatment and with this regime, the farmer
      would save up to 2.5 USD per animal during six months of dry season. CONCLUSIONS:
      The study revealed a high tick infestation among the TSHZ kept in extensive
      grazing systems in Mvomero district and that when treated with Ecotix(r) as pour
      on preparation using a two application regime per month, the tick control
      strategy was effective.

PMID- 23164197
TI  - Matrix to predict rapid radiographic progression of early rheumatoid arthritis
      patients from the community treated with methotrexate or leflunomide: results
      from the ESPOIR cohort.
AB  - INTRODUCTION: Early rheumatoid arthritis (RA) patients may show rapid
      radiographic progression (RRP) despite rapid initiation of synthetic disease
      modifying anti-rheumatic drugs (DMARDs). The present study aimed to develop a
      matrix to predict risk of RRP despite early DMARD initiation in real life
      settings. METHODS: The ESPOIR cohort included 813 patients from the community
      with early arthritis for < 6 months; 370 patients had early RA and had received
      methotrexate or leflunomide during the first year of follow-up. RRP was defined
      as an increase in the van der Heijde-modified Sharp score (vSHS) >= 5 points at 1
      year. Determinants of RRP were examined first by bivariate analysis, then
      multivariate stepwise logistic regression analysis. A visual matrix model was
      then developed to predict RRP in terms of patient baseline characteristics.
      RESULTS: We analyzed data for 370 patients. The mean Disease Activity Score in 28
      joints was 5.4 +/- 1.2, 18.1% of patients had typical RA erosion on radiographs
      and 86.4% satisfied the 2010 criteria of the American College of
      Rheumatology/European League Against Rheumatism. During the first year, mean
      change in vSHS was 1.6 +/- 5.5, and 41 patients (11.1%) showed RRP. A
      multivariate logistic regression model enabled the development of a matrix
      predicting RRP in terms of baseline swollen joint count, C-reactive protein
      level, anti-citrullinated peptide antibodies status, and erosions seen on
      radiography for patients with early RA who received DMARDs. CONCLUSIONS: The
      ESPOIR matrix may be a useful clinical practice tool to identify patients with
      early RA at high risk of RRP despite early DMARD initiation.

PMID- 23164199
TI  - User requirements for geo-collaborative work with spatio-temporal data in a web
      based virtual globe environment.
AB  - Web-based tools developed in the last couple of years offer unique opportunities
      to effectively support scientists in their effort to collaborate. Communication
      among environmental researchers often involves not only work with geographical
      (spatial), but also with temporal data and information. Literature still provides
      limited documentation when it comes to user requirements for effective geo
      collaborative work with spatio-temporal data. To start filling this gap, our
      study adopted a User-Centered Design approach and first explored the user
      requirements of environmental researchers working on distributed research
      projects for collaborative dissemination, exchange and work with spatio-temporal
      data. Our results show that system design will be mainly influenced by the nature
      and type of data users work with. From the end-users' perspective, optimal
      conversion of huge files of spatio-temporal data for further dissemination,
      accuracy of conversion, organization of content and security have a key role for
      effective geo-collaboration. 

PMID- 23164200
TI  - Interprofessional collaboration in the perianesthesia setting.

PMID- 23164201
TI  - Interprofessional collaborative practice.

PMID- 23164202
TI  - Focused anesthesia interview resource to improve efficiency and quality.
AB  - In an effort to reduce costs, many hospitals may use registered nurses (RNs) with
      little to no formal education or training in anesthetic or surgical risk to
      perform anesthesia preoperative interviews (APIs). This lack of education and
      training can result in day of surgery delays and cancellations because of
      suboptimal preparation of patients for anesthesia and surgery. The Focused
      Anesthesia Interview Resource (FAIR) establishes minimum educational preparation
      for conducting APIs through educational modules and electronic triggers that
      prompt further questions and consultation flags or comorbidities for which an
      anesthesia provider is consulted. The goal of this process improvement project
      was to determine if fidelity to the FAIR tool enhanced the ability of RNs to
      perform preoperative anesthesia interviews and, if so, did this result in
      decreased surgical cancellations and delays? Retrospectively, we assessed
      completion rates of the training modules and anesthesia preoperative records as
      well as day of surgery cancellation and delay rates before and after the
      implementation of the FAIR tool. All RNs who might rotate to the API clinic
      (n=33) were included in the sample. Nurse fidelity to completion of the training
      modules was high (91%). Five hundred anesthesia interview records were randomly
      selected, reviewed, and completion rates scored. Our pre-/post-quasi-experimental
      design compared record completion rates. After the implementation of FAIR,
      significant improvement in identification of patients with hypertension (P<.01)
      and cardiac disease (P<.05) was noted. In addition, cancellation rates declined
      from 3.33% to 2.31% (P<.05) and first case delays decreased from 7.54% to 6.99%,
      although this was not statistically significant. FAIR improved preoperative
      record completion rates and decreased surgical cancellations, which improved
      perioperative quality and efficiency.

PMID- 23164203
TI  - Perioperative pain management in the opioid-tolerant patient with chronic pain:
      an evidence-based practice project.
AB  - According to the Institute of Medicine (IOM) report on pain, chronic pain affects
      an estimated 116 million American adults and costs the nation more than $600
      billion each year in medical treatment and lost worker productivity. Many
      individuals with chronic pain undergo surgical procedures. Safe and effective
      treatment of their postoperative pain can present a significant challenge to the
      health care team but is essential to their optimal recovery. Administrators in a
      community hospital in central Pennsylvania identified a need to improve the care
      of their patients with chronic pain and supported a hospital-wide initiative to
      address various aspects of this population's hospital experience. This article
      presents the first phase of an evidence-based practice project that focused on
      improving the perioperative pain management in patients with chronic pain who
      receive long-acting opioids for the treatment of chronic pain before admission
      for surgery.

PMID- 23164204
TI  - Postanesthesia care unit discharge delay for nonclinical reasons.
AB  - Discharge of patients from the postanesthesia care unit (PACU) is often delayed
      for nonclinical reasons. This includes organizational issues such as patient
      transport, times of heavy workload for the ward and PACU nursing staff, surgical
      wards being unable to admit the patient, and clerical or administrative delays.
      We undertook a prospective study to evaluate PACU patient flow and the incidence
      and reasons behind delayed PACU discharge for nonclinical reasons in a tertiary
      referral hospital. Over a 4-month period, 2,783 patients were admitted
      postoperatively to our PACU. Delayed discharge because of nonclinical reasons was
      common, occurring in 421 (15%) patients. The median time of delayed discharge was
      70 minutes (range, 25 to 420 minutes). The most common reasons for delayed
      discharge of the patient to the ward were no bed in the designated postoperative
      ward for admittance (52%), ward nurses too busy to accept the patient (32%), and
      ward nurses' meal breaks (10%). Delayed PACU discharge for nonclinical reasons is
      common and occurs predominantly because of discharge planning and organizational
      and staffing issues in postoperative surgical wards. Improved discharge planning,
      restructured staffing, and alterations in operating room scheduling may minimize
      these nonclinical discharge delays.

PMID- 23164205
TI  - Bacteriostatic normal saline compared with buffered 1% lidocaine when injected
      intradermally as a local anesthetic to reduce pain during intravenous catheter
      insertion.
AB  - Pain associated with intravenous (IV) catheter insertion commonly causes fear and
      anxiety in presurgical patients. To reduce pain, a common procedure is
      intradermal injection of a local anesthesia. The aim of this study was to
      determine whether there is a significant difference in a patient's pain level
      after intradermal injection and IV catheter insertion when comparing
      intradermally injected bacteriostatic normal saline with 0.9% benzyl alcohol (a
      preservative added with an anesthetic component) with buffered 1% lidocaine to
      numb the IV line site. Using a double-blinded experimental design, 376 patients
      were randomly assigned to a bacteriostatic normal saline group or buffered 1%
      lidocaine group. Patients were given two needle sticks but rated only one pain
      score of either post-intradermal or post-IV injection using a 10-point numeric
      rating scale. A statistically significant difference was found in the IV pain
      scores, with subjects who received buffered 1% lidocaine reporting less pain than
      those who received bacteriostatic normal saline (P=.025). However, no significant
      difference was found in the intradermal pain scores (P=.792). Females reported
      higher IV pain scores than males only in the buffered 1% lidocaine group
      (P=.001). No statistically significant differences were found between the two
      anesthetics with intradermal and IV pain scores for IV placement side, site, IV
      within 30 days, needle gauge, previous IV experience or problems, vein
      visibility, or study nurse. This study determined that buffered 1% lidocaine was
      more effective than bacteriostatic normal saline in reducing pain during IV
      catheter insertion.

PMID- 23164206
TI  - Ambulatory perianesthesia electronic documentation--a two-part series. Part II:
      archiving your actions.

PMID- 23164207
TI  - Care of nonsurgical patients in the PACU.

PMID- 23164208
TI  - Brain gain: adolescent use of stimulants for achievement.

PMID- 23164209
TI  - The culture of nasty.

PMID- 23164210
TI  - Ketamine for pain management.

PMID- 23164211
TI  - Meaningful and useful measures of performance: ensuring an interprofessional
      approach to measure development.

PMID- 23164212
TI  - Restoration of photoreceptor structure and function in nonischaemic central
      retinal vein occlusion.

PMID- 23164214
TI  - You say you want a revolution?
AB  - I argue that Dixon et al. fail to maintain a careful distinction between the
      negative evaluation definition of "prejudice" and the implications of this
      definition for correcting the social ills that prejudice engenders. I also argue
      that they adduce little evidence to suggest that if prejudice were diminished,
      commensurate reductions in discrimination would not follow.

PMID- 23164213
TI  - Germline truncating-mutations in BRCA1 and MSH6 in a patient with early onset
      endometrial cancer.
AB  - BACKGROUND: Hereditary Breast and Ovarian Cancer Syndrome (HBOCS) and Hereditary
      Non-Polyposis Colorectal Cancer Syndrome (HNPCC, Lynch Syndrome) are two tumor
      predisposition syndromes responsible for the majority of hereditary breast and
      colorectal cancers. Carriers of both germline mutations in breast cancer genes
      BRCA1 or BRCA2 and in mismatch repair (MMR) genes MLH1, MSH2, MSH6 or PMS2 are
      very rare. CASE PRESENTATION: We identified germline mutations in BRCA1 and in
      MSH6 in a patient with increased risk for HBOC diagnosed with endometrial cancer
      at the age of 46 years. CONCLUSIONS: Although carriers of mutations in both MMR
      and BRCA genes are rare in Caucasian populations and anamnestical and
      histopathological findings may guide clinicians to identify these families, both
      syndromes can only be diagnosed through a complete gene analysis of the
      respective genes.

PMID- 23164215
TI  - Using cathodoluminescence spectroscopy of cretaceous calcareous microfossils to
      distinguish biogenic from early-diagenetic calcite.
AB  - A comparative cathodoluminescence (CL) spectroscopic study of extraordinarily
      well-preserved versus diagenetically altered Turonian (~92 Ma before present)
      calcitic and aragonitic microfossils was performed to document the
      cathodoluminescence characteristics of two common Cretaceous carbonate producers,
      foraminifera and calcareous dinoflagellates. Unaltered specimens reveal a
      conspicuous peak in the blue CL band at ~ 400 nm that has rarely been previously
      reported for biogenic carbonates. We interpret this luminescence as an indicative
      feature of the primary bio-mineralized shells of calcareous dinoflagellates and
      foraminifera. Orange luminescence as the second important CL emission band (~ 620
      nm) in calcite generally increases with diagenetic cement overgrowth and
      recrystallization but can also be present in unaltered material. Thus, orange CL
      of biogenic calcite is not an unequivocal diagenetic indicator. Accordingly,
      spectroscopic investigation of both the ~ 400 and ~ 620 nm peaks represents a
      more objective criterion to evaluate the degree of diagenetic alteration. The
      ratio of relative intensities of the blue CL versus orange CL can provide a
      semiquantitative measure with relative intensity ratios blue:orange >2 occurring
      in the least diagenetically altered microfossils. Comparison of unaltered
      specimens of separate species reveals elemental differences that potentially
      indicate species-specific biomineralization or habitats.

PMID- 23164216
TI  - Formation of N-nitrosamines from chlorination and chloramination of molecular
      weight fractions of natural organic matter.
AB  - N-Nitrosamines are a class of disinfection by-products (DBPs) that have been
      reported to be more toxic than the most commonly detected and regulated DBPs.
      Only a few studies investigating the formation of N-nitrosamines from
      disinfection of natural waters have been reported, and little is known about the
      role of natural organic matter (NOM) and the effects of its nature and reactivity
      on the formation of N-nitrosamines. This study investigated the influence of the
      molecular weight (MW) characteristics of NOM on the formation of eight species of
      N-nitrosamines from chlorination and chloramination, and is the first to report
      on the formation of eight N-nitrosamines from chlorination and chloramination of
      MW fractions of NOM. Isolated NOM from three different source waters in Western
      Australia was fractionated into several apparent MW (AMW) fractions using
      preparative-scale high performance size exclusion chromatography. These AMW
      fractions of NOM were then treated with chlorine or chloramine, and analysed for
      eight species of N-nitrosamines. Among these N-nitrosamines, N
      nitrosodimethylamine (NDMA) was the most frequently detected. All AMW fractions
      of NOM produced N-nitrosamines upon chlorination and chloramination. Regardless
      of AMW characteristics, chloramination demonstrated a higher potential to form N
      nitrosamines than chlorination, and a higher frequency of detection of the N
      nitrosamines species was also observed in chloramination. The results showed that
      inorganic nitrogen may play an important role in the formation of N-nitrosamines,
      while organic nitrogen is not necessarily a good indicator for their formation.
      Since chlorination has less potential to form N-nitrosamines, chloramination in
      pre-chlorination mode was recommended to minimise the formation of N
      nitrosamines. There was no clear trend in the formation of N-nitrosamines from
      chlorination of AMW fractions of NOM. However, during chloramination, NOM
      fractions with AMW <2.5 kDa were found to produce higher concentrations of NDMA
      and total N-nitrosamines. The precursor materials of N-nitrosamines appeared to
      be more abundant in the low to medium MW fractions of NOM, which correspond to
      the fractions that are most difficult to remove using conventional drinking water
      treatment processes. Alternative or advanced treatment processes that target the
      removal of low to medium MW NOM including activated carbon adsorption,
      biofiltration, reverse osmosis, and nanofiltration, can be employed to minimise
      the formation of N-nitrosamines.

PMID- 23164217
TI  - Source water quality shaping different fouling scenarios in a full-scale
      desalination plant at the Red Sea.
AB  - The complexity of Reverse Osmosis (RO) membrane fouling phenomenon has been
      widely studied and several factors influencing it have been reported by many
      researchers. This original study involves the investigation of two different
      fouling profiles produced at a seawater RO desalination plant installed on a
      floating mobile barge. The plant was moved along the coastline of the Red Sea in
      Saudi Arabia. The two locations where the barge was anchored showed different
      water quality. At the second location, two modules were harvested. One of the
      modules was pre-fouled by inorganics during plant operation at the previous site
      while the other was installed at the second site. Fouled membranes were subjected
      to a wide range of chemical and microbiological characterization procedures.
      Drastically different fouling patterns were observed in the two membranes which
      indicates the influence of source water quality on membrane surface modification
      and on fouling of RO membranes.

PMID- 23164218
TI  - Free chlorine inactivation of fungi in drinking water sources.
AB  - The effectiveness of free chlorine for the inactivation of fungi present in
      settled surface water was tested. In addition, free chlorine inactivation rate
      constants of Cladosporium tenuissimum, Cladosporium cladosporioides, Phoma
      glomerata, Aspergillus terreus, Aspergillus fumigatus, Penicillium griseofulvum,
      and Penicillium citrinum that were found to occur in different source waters were
      determined in different water matrices (laboratory grade water and settled
      water). The effect of using different disinfectant concentrations (1 and 3 mg/l),
      temperatures (21 and 4  degrees C), and pH levels (6 and 7) was addressed. The
      sensitivity degree of different fungi isolates to chlorine disinfection varied
      among different genera with some species showing a higher resistance to
      disinfection and others expected to be more prone to protection from inactivation
      by the water matrix components. When the disinfection efficiency measured in
      terms of the chlorine concentration and contact time (Ct) values needed to
      achieve 99% inactivation were compared with the Ct values reported as being able
      to achieve the same degree of inactivation of other microorganisms, fungi were
      found to be more resistant to chlorine inactivation than bacteria and viruses and
      less resistant than Cryptosporidium oocysts.

PMID- 23164219
TI  - Evaluation of BACTECTM MGITTM 960 and the nitrate reductase assay in the National
      Laboratory Network of Colombia.
AB  - SETTING: The Mycobacteria Group of the National Reference Laboratory, National
      Laboratory Network, National Institute of Health and the Public Health
      Laboratories of Antioquia, Atlantico and Valle del Cauca, Colombia. OBJECTIVE: To
      compare BACTECTM MGITTM (Mycobacteria  Growth Indicator Tube) 960 and the nitrate
      reductase assay (NRA) with the proportion method on Lowenstein-Jensen medium and
      to determine resistance to first-line anti-tuberculosis drugs. METHODS:
      Evaluation of diagnostic assays using time-adjusted convenience sampling. We
      analysed  183 isolates of Mycobacterium tuberculosis to compare MGIT 960 and NRA
      with the proportion method. RESULTS: MGIT 960 had a sensitivity and specificity
      of 90% for isoniazid (INH), and respectively 100% and 99.4% for rifampicin (RMP).
      NRA had a sensitivity and a specificity of respectively  86% and 94.7% for INH
      and 100% and 99% for RMP. CONCLUSION: Given its high sensitivity and specificity,
      and easy accessibility and interpretation of results, the NRA should be
      implemented in the National Laboratory Network for the detection of resistance to
      INH and RMP.

PMID- 23164220
TI  - Strategies for monitoring and updating clinical practice guidelines: a systematic
      review.
AB  - BACKGROUND: Scientific knowledge is in constant change. The flow of new
      information requires a frequent re-evaluation of the available research results.
      Clinical practice guidelines (CPGs) are not exempted from this phenomenon and
      need to be kept updated to maintain the validity of their recommendations. The
      objective of our review is to systematically identify, describe and assess
      strategies for monitoring and updating CPGs. STUDY DESIGN AND SETTING: We
      conducted a systematic review of studies evaluating one or more methods of
      updating (with or without monitoring) CPGs or recommendations. We searched
      MEDLINE (PubMed) and The Cochrane Methodology Register (The Cochrane Library)
      from 1966 to June 2012. Additionally, we hand-searched reference lists of the
      included studies and the Guidelines International Network book of abstracts. If
      necessary, we contacted study authors to obtain additional information. RESULTS:
      We included a total of eight studies. Four evaluated if CPGs were out of date,
      three updated CPGs, and one continuously monitored and updated CPGs. The most
      detailed reported phase of the process was the identification of new evidence. As
      opposed to studies updating guidelines, studies evaluating if CPGs were out of
      date applied restricted searches. Only one study compared a restricted versus an
      exhaustive search suggesting that a restricted search is sufficient to assess
      recommendations' Validity. One study analyzed the survival time of CPGs and
      suggested that these should be reassessed every three years. CONCLUSIONS: There
      is limited evidence about the optimal strategies for monitoring and updating
      clinical practice guidelines. A restricted search is likely to be sufficient to
      monitor new evidence and assess the need to update, however, more information is
      needed about the timing and type of search. Only the exhaustive search strategy
      has been assessed for the update of CPGs. The development and evaluation of more
      efficient strategies is needed to improve the timeliness and reduce the burden of
      maintaining the validity of CPGs.

PMID- 23164222
TI  - Effect of prolactin-release inhibition on milk production and mammary gland
      involution at drying-off in cows.
AB  - The end of each lactation is a challenging period for high-yielding cows as they
      are often dried off while still producing significant quantities of milk and,
      consequently, are highly susceptible to new intramammary infections. Once
      involution is complete, the mammary gland becomes much more resistant to
      infection. Therefore, it is critically important to develop strategies aimed at
      reducing milk production before drying-off and to accelerate mammary gland
      involution. This study assessed the effect of inhibition of the lactogenic signal
      driven by prolactin (PRL) on milk production and concentrations of involution
      markers in mammary secretions. Sixteen Holstein cows in late lactation were
      assigned to treatments based on milk yield, somatic cell count, and parity. Of
      those cows, 8 received twice-daily intramuscular injections (2 mg per injection)
      of quinagolide, a specific inhibitor of PRL release, from 4 d before drying-off
      to 3 d after (Quin). The other 8 cows received injections of the solvent (water,
      control). Blood and milk (mammary secretion) samples were collected on the last 5
      d before and on d 1, 3, 5, 7, 10, and 14 after the last milking. Additionally, on
      the day preceding the first injection and on the following day, several blood
      samples were collected around milking time. Quinagolide reduced basal serum PRL
      concentrations on all injection days as well as PRL released in blood during
      milking. The PRL inhibitor decreased milk production before drying-off, which
      averaged, over the last 3 d of lactation, 19.3 and 15.5 kg/d for the control and
      Quin cows, respectively. Quinagolide had no significant effect on milk
      citrate:lactoferrin and Na:K ratios, which decreased and increased, respectively,
      during the first 2 wk of the dry period. Nevertheless, the increases in the
      number of somatic cells and bovine serum albumin concentration during early
      involution were greater and matrix metalloproteinase-2 activity tended to be
      greater in mammary secretions of the Quin cows compared with the control cows.
      This experiment shows that inhibition of PRL release decreases milk production of
      cows in late lactation. Changes in the composition of mammary secretions suggest
      that this approach also hastens mammary gland involution.

PMID- 23164221
TI  - Breast cancer risk in relation to occupations with exposure to carcinogens and
      endocrine disruptors: a Canadian case-control study.
AB  - BACKGROUND: Endocrine disrupting chemicals and carcinogens, some of which may not
      yet have been classified as such, are present in many occupational environments
      and could increase breast cancer risk. Prior research has identified associations
      with breast cancer and work in agricultural and industrial settings. The purpose
      of this study was to further characterize possible links between breast cancer
      risk and occupation, particularly in farming and manufacturing, as well as to
      examine the impacts of early agricultural exposures, and exposure effects that
      are specific to the endocrine receptor status of tumours. METHODS: 1005 breast
      cancer cases referred by a regional cancer center and 1146 randomly-selected
      community controls provided detailed data including occupational and reproductive
      histories. All reported jobs were industry- and occupation-coded for the
      construction of cumulative exposure metrics representing likely exposure to
      carcinogens and endocrine disruptors. In a frequency-matched case-control design,
      exposure effects were estimated using conditional logistic regression. RESULTS:
      Across all sectors, women in jobs with potentially high exposures to carcinogens
      and endocrine disruptors had elevated breast cancer risk (OR = 1.42; 95% CI, 1.18
      1.73, for 10 years exposure duration). Specific sectors with elevated risk
      included: agriculture (OR = 1.36; 95% CI, 1.01-1.82); bars-gambling (OR = 2.28;
      95% CI, 0.94-5.53); automotive plastics manufacturing (OR = 2.68; 95% CI, 1.47
      4.88), food canning (OR = 2.35; 95% CI, 1.00-5.53), and metalworking (OR = 1.73;
      95% CI, 1.02-2.92). Estrogen receptor status of tumors with elevated risk
      differed by occupational grouping. Premenopausal breast cancer risk was highest
      for automotive plastics (OR = 4.76; 95% CI, 1.58-14.4) and food canning (OR =
      5.70; 95% CI, 1.03-31.5). CONCLUSIONS: These observations support hypotheses
      linking breast cancer risk and exposures likely to include carcinogens and
      endocrine disruptors, and demonstrate the value of detailed work histories in
      environmental and occupational epidemiology.

PMID- 23164223
TI  - Effect of milk feeding level on development of feeding behavior in dairy calves.
AB  - Evidence exists that early life experiences may influence development of
      characteristic feeding patterns in dairy cattle. The objective of this study was
      to determine the effect of milk feeding level on performance and development of
      feeding patterns in dairy calves. Twenty Holstein bull calves were assigned at
      birth to a milk replacer feeding level, fed via a teat: (1) ad libitum (ADL) or
      (2) restricted feeding at 5 L/d (0.75 kg of milk replacer) in 2 feedings/d (RES).
      All calves were offered concentrate ad libitum during the milk feeding stage.
      Calves were weaned gradually during wk 7 and then fed a pelleted diet ad libitum
      for 7 wk. Calves were weighed 2 times/wk. Feed and milk intakes were recorded
      daily. Feeding behavior was recorded from video for 5 d in each of wk 3, 6, 8,
      11, and 14. Calves fed ADL consumed 2.6 times more milk, had greater weight gain
      (1.2 vs. 0.6 kg/d), and consumed less solid feed (45.2 vs. 98.0 g/d) during the
      milk feeding period than did calves fed RES. As expected, providing milk ADL
      resulted in more frequent meals (in wk 6, 7.1 vs. 2.0) and more evenly
      distributed diurnal patterns of feeding activity compared with the RES milk
      level. When considering all sucking bouts (milk feeding and nonnutritive
      sucking), no difference was observed between treatments in daily bout frequency
      or sucking time/bout. Postweaning, calves fed RES had initially greater rate of
      intake (24.9 vs. 17.8 g/min) and meal size (160.8 vs. 117.2 g/meal). Diurnal
      feeding patterns also differed in the first week after weaning, with ADL calves
      feeding less continuously at the time of feed delivery. Meal characteristics and
      diurnal patterns of feeding activity were similar between calves by the end of
      the trial. However, milk feeding level had a longer-term effect on variability in
      feeding behavior, with calves fed RES having greater day-to-day variability in
      feeding time and meal size. Variability of meal characteristics also decreased
      over time across treatments. These results suggest that milk feeding level may
      have a short-term influence on postweaning feeding behavior. However, differences
      in early feeding patterns due to milk feeding level do not appear to affect
      longer-term development of feeding patterns.

PMID- 23164224
TI  - Short communication: Large-scale study on effects of metritis on reproduction in
      Danish Holstein cows.
AB  - A total of 398,237 lactations of Danish Holstein dairy cows were studied with the
      main objective to investigate the effects of metritis on 2 fertility variables:
      interval from calving to first insemination (CFI) and nonreturn rate at 56 d
      after first insemination (NR56), adjusting for milk production and body condition
      score as confounders. Metritis was defined as a score of at least 5 (indicating
      purulent vaginal discharge with abnormal smell) on the Danish uterine score scale
      (from 0 to 9, used to evaluate vaginal discharge in the first 19 d postpartum on
      all fresh cows in herds participating in a national herd health program). Cows
      with metritis in early lactation presented a significant delay in first
      insemination (hazard ratio of 0.80) and a significantly reduced probability of
      success at first insemination. The effect of metritis was also present after
      adjusting for possible effects of body condition score, milk production in the
      first month of lactation, parity, herd, and year-season. Only a small part of the
      observed effect of metritis could be explained by variation in body condition
      score at calving and milk production in the first month after calving. The
      results from this large-scale study underscore the deleterious effects of
      metritis on the fertility variables CFI and NR56.

PMID- 23164225
TI  - Milk protein responses in dairy cows to changes in postruminal supplies of
      arginine, isoleucine, and valine.
AB  - An ideal profile of essential AA (EAA) can improve the efficiency of
      metabolizable protein (or PDIE, the equivalent in the INRA feeding system)
      utilization in dairy cows. Compared with other EAA, existing recommendations for
      the requirements of Arg, Ile, and Val are few and inconsistent. Four multiparous
      Holstein dairy cows at 22+/-6 wk of lactation received 4 treatments (duodenal
      infusions of 445+/-22.4 g/d of an EAA mixture complementing a low-protein diet in
      a 4*4 Latin square design with a period length of 1 wk). The control treatment
      provided a balanced supply (in % of PDIE) of 5.1% Arg, 5.2% Ile, and 5.9% Val,
      whereas in the 3 subsequent treatments of -Arg, -Ile, and -Val, the
      concentrations of these 3 EAA were reduced to 3.5, 4.1, and 4.5%, respectively.
      All treatments were made isonitrogenous and were balanced to provide 7 other EAA
      (Lys, Met, His, Leu, Phe, Thr, and Trp), according to the recommendations
      described in the literature. Combined, the diet and the infusions provided 14.3+/
      0.1% crude protein on a dry matter basis, and 66.0+/-1.2 g of PDIE/Mcal of net
      energy for lactation. Neither dry matter intake (19.2 kg/d) nor milk yield
      (30.4+/-0.4 kg/d) was affected by treatments. The -Arg and -Ile treatments did
      not modify milk protein synthesis or the efficiency of N utilization. However,
      the -Val treatment decreased milk protein content by 4.9% and milk crude protein
      content by 4.3%, and tended to decrease the efficiency of N use for milk protein
      yield by 3.7% (compared with the control). These effects of Val were related to a
      decrease in the plasma concentration of Val as well as a trend toward decreasing
      plasma concentrations of Met, His, and the sum of all EAA and nonessential AA in
      the -Val treatment, which indicates a different utilization of all AA in response
      to the Val deficit. The deletion of Ile, compared with the deletion of Val,
      tended to decrease the milk protein-to-fat ratio by 3.8%. In conclusion, the
      supply of Arg at 3.5% of PDIE was not limiting for milk protein synthesis. The
      slight effect on the milk protein-to-fat ratio caused by decreasing the supply of
      Ile suggests a need to reevaluate the Ile requirement more precisely. A low Val
      supply could be limiting for milk protein synthesis, provided that the
      requirements of Lys, Met, and His are met.

PMID- 23164226
TI  - Short communication: Effect of supplementation with Lactobacillus casei Shirota
      on insulin sensitivity, beta-cell function, and markers of endothelial function
      and inflammation in subjects with metabolic syndrome--a pilot study.
AB  - Based on animal studies, intake of probiotic bacteria was suggested to improve
      insulin sensitivity by reducing endotoxinemia and inflammation. The objective of
      this study was to determine the effects of supplementation with the probiotic
      strain Lactobacillus casei Shirota (LcS) over 12 wk on insulin sensitivity, beta
      cell function, inflammation, and endothelial dysfunction parameters in subjects
      with metabolic syndrome. In a randomized-controlled study, 30 subjects with
      metabolic syndrome either received Lactobacillus casei Shirota 3 times daily for
      12 wk or served as controls with standard medical therapy. Fasting blood samples
      were taken and a 75-g oral glucose tolerance test was performed to derive indices
      for insulin sensitivity and beta-cell function. In addition, parameters to assess
      endothelial function and inflammation markers were determined. Even though the
      insulin sensitivity index significantly improved after 3 mo of probiotic
      supplementation (0.058+/-0.021 vs. 0.038+/-0.025), the change was not
      significantly different compared with the control group. No improvements were
      seen in additional indices of insulin sensitivity (quantitative insulin
      sensitivity check index, insulin sensitivity by oral glucose tolerance test, and
      homeostasis model assessment for insulin resistance) and beta-cell function
      (first and second phase insulin secretion, and homeostasis model assessment for
      beta-cell function). Probiotic supplementation resulted in a significant
      reduction in soluble vascular cell adhesion molecule-1 (sVCAM-1) level (1,614+/
      343 vs. 1,418+/-265 ng/mL). No significant changes in parameters used to assess
      low-grade inflammation or endothelial dysfunction were observed. Intake of LcS
      for 12 wk in subjects with metabolic syndrome did not improve insulin
      sensitivity, beta-cell function, endothelial function, or inflammation markers in
      this trial.

PMID- 23164227
TI  - Short communication: The effect of premilking with a teat cup-like device, in a
      novel robotic rotary, on attachment accuracy and milk removal.
AB  - This study investigated the effects of premilking teat preparation on attachment
      accuracy and milk removal characteristics for individual cows in a novel 16-bail
      prototype robotic rotary (RR; automatic milking rotary system; DeLaval AMR,
      Tumba, Sweden). The first commercial versions of the RR systems will have the
      option of purchasing and installing a teat preparation module (TPM) for
      premilking stimulation and cleaning of teats. It is expected that attachment of
      teat cups would be faster and more successful with the use of a TPM, and that the
      efficiency of milk removal, in terms of average and peak milk flow rates, would
      increase. We observed a significant effect of treatment (no wash vs. wash) and
      individual quarters on attachment success: cows exposed to the wash treatment had
      up to 1.5 times higher odds of being successfully attached. The attachment was
      not only more successful but was also found to be 4.3 s faster after cows were
      exposed to the wash treatment. Average milk flow rate was not affected by the
      wash treatment. Nevertheless, a significant interaction was found between wash
      treatment and milking interval affecting the peak milk flow (kg/min) of
      individual cows. This interaction showed that cows with a milking interval <=8 h
      subjected to the wash treatment had significantly higher peak flow rates (300
      g/min increase) compared with cows in the same milking interval category with no
      wash treatment. The relationship between premilking stimulation and attachment
      success shown in this study will increase awareness (of both farmers and
      developers of the technology) of the importance of teat cleaning within the RR.
      The effects of the improved system performance should be taken into account
      (alongside the capital investment cost) when deciding to install a RR equipped
      (or not) with a TPM.

PMID- 23164228
TI  - Effect of the inclusion of quebracho tannins in a diet rich in linoleic acid on
      milk fatty acid composition in dairy ewes.
AB  - Despite controversy surrounding the ability of tannins to modulate the fatty acid
      (FA) profile of ruminant-derived products, reports on this issue are still very
      limited for dairy sheep. This study was conducted to examine the effect of the
      inclusion of quebracho tannins in a diet rich in linoleic acid on ewe performance
      and milk FA composition. Thirty-six lactating ewes were distributed into 6 lots
      and allocated to 2 treatments (3 lots/treatment): control or quebracho. All sheep
      received a total mixed ration based on alfalfa hay and a concentrate
      (forage:concentrate ratio of 40:60) supplemented with 20 g of sunflower oil/kg of
      dry matter plus 0 (control diet) or 20 g of an extract of quebracho tannins/kg of
      dry matter (QUE diet). Milk production and composition were analyzed on d 0, 3,
      6, 9, 12, 15, 18, 21, 24, and 27 on treatments, and milk FA profile on d 0, 3, 6,
      12, 18, and 27. On d 27, samples of rumen fluid were collected for pH, and
      lactate, ammonia, and volatile FA concentration analysis. Feeding the QUE diet
      had no apparent effect on animal performance and hardly modified ruminal
      fermentation characteristics, except for a reduction in the molar proportions of
      minor volatile FA. Dietary tannins increased the milk concentration of several
      18:1 and 18:2 isomers and decreased that of branched-chain FA. Some of these
      changes were relatively constant throughout the experiment (e.g., cis-12 18:1 and
      trans-9,cis-12 18:2), whereas others varied over time (e.g., trans-10 18:1, which
      increased gradually with the QUE diet). Significant differences between
      treatments in trans-11 18:1 and cis-9,trans-11 conjugated linoleic acid were only
      observed on d 3. Overall, addition of quebracho tannins to a diet rich in
      linoleic acid did not prove useful to beneficially modify milk FA composition,
      especially over the long term.

PMID- 23164229
TI  - Effect of photoperiod and heat stress in the third trimester of gestation on milk
      production and circulating hormones in dairy goats.
AB  - The influence of photoperiod manipulation in the dry period was examined in dairy
      goats experiencing environmental heat stress. Multiparous Israeli Saanen goats
      were blocked at dry off (~60 d prepartum) into 2 groups of 4 goats each based on
      body weight, previous milk production, and detected embryo number. Treatments
      consisted of long-day (16 h light:8 h dark) and short-day (8 h light:16 h dark)
      photoperiods (LDPP and SDPP, respectively). Heat-stress conditions were applied
      by manipulating the environment of metabolic rooms to reach a maximum temperature
      of 37 degrees C between 1000 and 2200 h, and a minimum of 23 degrees C and 70.3%
      relative humidity. All goats were returned to ambient photoperiod after kidding,
      milked twice daily, and milk yield was automatically recorded. Dry matter intake
      during the dry period was similar between treatments, averaging 1,114 g/d. Milk
      production was significantly higher in the SDPP than the LDPP group (2,172 vs.
      1,550 g/d) during the 12-wk experimental period. Milk protein and fat contents
      were similar in both groups and averaged 3.63 and 4.34%, respectively, whereas
      milk lactose was higher in the LDPP group (4.77 vs. 4.67%). Heart rates were
      similar between treatments and averaged 112.6 beats per minute (BPM). Respiration
      rates were lower in the morning (58.4 BPM) compared with the afternoon (91.2 BPM)
      and were not influenced by photoperiod. Rectal temperature was higher for the
      LDPP than the SDPP group (40.4 vs. 39.6 degrees C). The thyroid hormone level
      (mean +/- SE) was similar in both groups during the dry period, but higher during
      lactation in the LDPP goats up to 40 d postpartum (110+/-6.59 vs. 156+/-8.76
      ng/mL). Plasma IGF-1 (mean +/- SE) was higher in the LDPP group (279+/-62 vs.
      162+/-27 ng/mL in SDPP) during the dry period but was similar postkidding,
      averaging 132+/-24 ng/mL. Plasma prolactin level (mean +/- SE) was higher in the
      LDPP than the SDPP group during the dry period (17.2+/-1.6 vs. 10.6+/-0.99
      ng/mL), whereas it was similar throughout lactation (0.61+/-0.28 ng/mL). These
      data support the idea that SDPP manipulation during heat load in dry goats can be
      used as an abatement strategy to reduce the carryover effect of heat stress
      observed during the subsequent lactation. The higher milk production in SDPP
      goats is explained by changes in circulating prolactin profile rather than
      differences in feed intake or secretion of insulin-like growth factor 1.

PMID- 23164230
TI  - Effect of cereal grain type and corn grain harvesting and processing methods on
      intake, digestion, and milk production by dairy cows through a meta-analysis.
AB  - A meta-analysis was performed to determine the influence of cereal grain type and
      corn grain harvesting and processing methods, dietary starch, rumen-digestible
      starch, and forage NDF concentrations on intake, digestion, and lactation
      performance by dairy cows using a data set comprising 414 treatment means from
      102 peer-reviewed journal reports from 2000 to 2011. Categories for corn
      processing were dry ground, cracked or rolled corn (DRY), high-moisture shelled
      or ear corn (ENS), and steam-flaked or -rolled corn (STM); categories for kernel
      mean particle size were 500 to 1,000, 1,000 to 1,500, 1,500 to 2,000, 3,000 to
      3,500, and 3,500 to 4,000 um for dry corn and <2,000 and >=2,000 um for ensiled
      corn. Dietary starch and forage NDF concentrations were used as continuous
      variables. Data were analyzed using PROC MIXED in SAS (SAS Institute Inc., Cary,
      NC), with treatment as fixed and trial as random effects. Total-tract starch
      digestibility was reduced and milk fat content was greater for DRY compared with
      ENS or STM. Total-tract digestibility of dietary starch was reduced for both DRY
      and ENS as particle size increased. Increased dietary starch concentrations
      increased milk yield and protein content, but decreased ruminal and total-tract
      NDF digestibilities and milk fat content. Dry matter intake, total-tract starch
      digestibility, and milk protein concentration decreased as forage NDF in the diet
      increased. Total-tract starch digestibility was positively related to ruminal
      (percentage of starch intake) and postruminal (percentage of duodenal flow)
      starch digestibilities.

PMID- 23164231
TI  - Effect of iron saturation level of lactoferrin on osteogenic activity in vitro
      and in vivo.
AB  - We studied the effect of iron saturation level on the osteogenic activity of
      lactoferrin (LF) in vitro and in vivo. Different iron saturation levels of LF
      (1.0, 9.0, 38, 58, and 96%) were prepared as the following samples: apo-LF, LF-9,
      LF-38, LF-58, and holo-LF. Using the 3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide (MTT) assay, we observed that the stimulating
      osteoblast proliferation activity of LF in vitro decreased with increasing iron
      saturation level at 100 and 1,000 MUg/mL. In vivo, 4-wk-old ICR Swiss male mice
      were randomly divided into 4 groups: blank control (physiological saline),
      negative control (BSA), apo-LF, and holo-LF. Four groups of mice were injected
      subcutaneously with physiological saline, BSA, apo-LF, or holo-LF over the
      calvarial surface twice a day for 5 consecutive days at a dose of 4 mg/kg per
      day. Bone histomorphometry showed that new bone formation (assessed using
      tetracycline-HCl labels) tended to be stronger with apo-LF than with holo-LF.
      Using fluorescence spectroscopy and circular dichroism measurements, we found
      that exposure of tryptophan increased, alpha-helix content increased, but beta
      structure content decreased with increasing iron saturation level. These findings
      indicated that the osteogenic activity of LF decreases with increasing iron
      saturation level in vitro and in vivo, which may be related to conformational
      changes in LF.

PMID- 23164232
TI  - Nitrogen partitioning and milk production of dairy cows grazing simple and
      diverse pastures.
AB  - Research was conducted to examine the effects of a diverse pasture mix on dry
      matter intake, milk yield, and N partitioning of lactating dairy cows. A pasture
      containing only ryegrass and white clover (RG), or high-sugar ryegrass and white
      clover (HS), was compared with a diverse pasture mix (HSD) including chicory,
      plantain, lotus, high-sugar ryegrass, and white clover. The experiment was
      conducted over a 10-d period using 3 groups of 12 cows in late lactation. No
      difference was observed in dry matter (14.3 kg of dry matter/cow per day) or N
      (583 g of N/cow per day) intake between treatments. The cows grazing the HSD
      pasture had an increased milk yield (16.9 kg/d) compared with those grazing the
      simple RG and HS pastures (15.2 and 14.7 kg/d, respectively). However, no
      differences were observed in milk solids yield for the 3 treatments. A tendency
      toward greater milk protein yields in the HSD group resulted in improved N use
      efficiency for milk of 20.4% from the cows fed HSD, compared with 17.8 and 16.7%
      from cows in the RG and HS treatments, respectively. Urinary N excretion was
      lower from the cows fed HSD, at 353.8 g/d, compared with 438.3 and 426.6 g/d for
      cows fed RG and HS, respectively. These results suggest that the use of pastures
      containing chicory, lotus, and plantain can contribute to the goal of reducing N
      losses from cows in late lactation.

PMID- 23164233
TI  - Evaluation of clustering of new intramammary infections in the bovine udder,
      including the impact of previous infections, herd prevalence, and somatic cell
      count on their development.
AB  - Evidence in the literature exists to support the theory that mastitis and
      intramammary infection (IMI) tend to cluster within herds, within cows, and
      within quarters, facts which may have overarching ramifications on mastitis
      management in modern dairy herds. Most previous studies, however, have been
      carried out on prevalent IMI instead of new IMI (NIMI), although reducing
      incidence of NIMI is a major step toward controlling mastitis. The Canadian
      Bovine Mastitis Research Network (Saint-Hyacinthe, QC, Canada) has a large
      mastitis database derived from a 2-yr data collection on a national cohort of
      dairy farms, and data from this initiative were used to investigate the effect of
      clustering on the acquisition of NIMI. Longitudinal milk samplings of clinically
      normal udders taken over several 6-wk periods as well as samples from cows pre
      dry-off and postcalving were used (n=73,772 quarter milk samples). Multilevel
      logistic models were used to evaluate the effect of location of IMI in quarters
      of the bovine udder previous to occurrence of an NIMI with Staphylococcus aureus,
      coagulase-negative staphylococci, and Corynebacterium spp. Several factors were
      investigated, including the number and location of quarters infected with the
      pathogen of interest before occurrence of an NIMI, the number of quarters
      infected with any other pathogen before occurrence of an NIMI (a measure of
      susceptibility), somatic cell count of the quarter before occurrence of an NIMI,
      somatic cell count of the other 3 quarters before occurrence of an NIMI,
      prevalence of the specific pathogen in the herd, and the average somatic cell
      count of the herd. The amount of variation occurring at different levels (herd,
      cow, and quarter) for the various pathogens was also calculated. The presence of
      an IMI in the ipsilateral quarter was associated with an elevated risk of an NIMI
      occurring for all pathogens investigated. Risk of an NIMI increased considerably
      as herd prevalence of the pathogen rose. Substantial clustering was found at all
      levels, with roughly equal amounts of variation found in all 3 levels for
      coagulase-negative staphylococci, most variation at the cow-level for
      Corynebacterium spp., and most variation found at the quarter-level for Staph.
      aureus. Simulation was used to calculate exact values of intraclass correlation
      coefficients to estimate clustering within cows and within quarters--these exact
      values were, for the most part, lower than estimates calculated using the latent
      variable approach, but also increased as pathogen prevalence and number of
      infections in a cow at the previous sampling increased. These results of these
      analyses can be used to inform approaches to preventing NIMI in modern dairy
      operations.

PMID- 23164234
TI  - Analysis of individual classification of lameness using automatic measurement of
      back posture in dairy cattle.
AB  - Currently, diagnosis of lameness at an early stage in dairy cows relies on visual
      observation by the farmer, which is time consuming and often omitted. Many
      studies have tried to develop automatic cow lameness detection systems. However,
      those studies apply thresholds to the whole population to detect whether or not
      an individual cow is lame. Therefore, the objective of this study was to develop
      and test an individualized version of the body movement pattern score, which uses
      back posture to classify lameness into 3 classes, and to compare both the
      population and the individual approach under farm conditions. In a data set of
      223 videos from 90 cows, 76% of cows were correctly classified, with an 83% true
      positive rate and 22% false positive rate when using the population approach. A
      new data set, containing 105 videos of 8 cows that had moved through all 3
      lameness classes, was used for an ANOVA on the 3 different classes, showing that
      body movement pattern scores differed significantly among cows. Moreover, the
      classification accuracy and the true positive rate increased by 10 percentage
      units up to 91%, and the false positive rate decreased by 4 percentage units down
      to 6% when based on an individual threshold compared with a population threshold.

PMID- 23164235
TI  - Prejudice reduction, collective action, and then what?
AB  - Despite downsides, it must, on balance, be good to reduce prejudice. Despite
      upsides, collective action can also have destructive outcomes. Improving
      intergroup relations requires multiple levels of analysis involving a broader
      approach to prejudice reduction, awareness of potential conflict escalation,
      development of intergroup understanding, and promotion of a wider human rights
      perspective.

PMID- 23164237
TI  - The micturition switch and its forebrain influences.
AB  - Dr DeGroat and Wickens has reviewed the central neural mechanisms controlling the
      lower urinary tract with a major focus on the brain stem circuitry that mediates
      the switch-like characteristics of micturition, in particular the periaqueductal
      grey and the pontine micturition centre (de 2012). The review culminates in a
      computer model of how the brainstem switch operates in animals in which forebrain
      influences on micturition have been removed by decerebration. In this
      complementary paper, we review the mechanisms of forebrain involvement in the
      voluntary control of human micturition and the maintenance of continence with
      evidence based heavily on the results of functional brain imaging experiments.

PMID- 23164238
TI  - [Application of clinical practice guidelines in chronic obstructive pulmonary
      disease].

PMID- 23164236
TI  - Polymorphisms in peptidylarginine deiminase associate with rheumatoid arthritis
      in diverse Asian populations: evidence from MyEIRA study and meta-analysis.
AB  - INTRODUCTION: The majority of our knowledge regarding disease-related mechanisms
      of uncontrolled citrullination and anti-citrullinated protein antibody
      development in rheumatoid arthritis (RA) was investigated in Caucasian
      populations. However, peptidylarginine deiminase (PADI) type 4 gene polymorphisms
      are associated with RA in East Asian populations and weak or no association was
      found in Caucasian populations. This study explores the association between the
      PADI4 polymorphisms and RA risk in a multiethnic population residing in South
      East Asia with the goal of elucidating generalizability of association in non
      Caucasian populations. METHODS: A total of 320 SNPs from the PADI locus
      (including PADI1, PADI2, PADI3, PADI4 and PADI6 genes) were genotyped in 1,238 RA
      cases and 1,571 control subjects from the Malaysian Epidemiological Investigation
      of Rheumatoid Arthritis (MyEIRA) case-control study. Additionally, we conducted
      meta-analysis of our data together with the previously published studies of RA
      from East Asian populations. RESULTS: The overall odds ratio (ORoverall) for the
      PADI4 (rs2240340) allelic model was 1.11 (95% confidence interval (CI) = 1.00 to
      1.23, P = 0.04) and for the genotypic model was 1.20 (95% CI = 1.01 to 1.44, P =
      0.04). Haplotype analysis for four selected PADI4 SNPs revealed a significant
      association of one with susceptibility (P = 0.001) and of another with a
      protective effect (P = 0.02). The RA susceptibility was further confirmed when
      combined meta-analysis was performed using these data together with data from
      five previously published studies from Asia comprising 5,192 RA cases and 4,317
      control subjects (ORoverall = 1.23 (95% CI = 1.16 to 1.31, Pheterogeneity = 0.08)
      and 1.31 (95% CI = 1.20 to 1.44, Pheterogeneity = 0.32) in allele and genotype
      based models, respectively). In addition, we also detected a novel association of
      PADI2 genetic variant rs1005753 with RA (ORoverall = 0.87 (95% CI = 0.77 to
      0.99)). CONCLUSION: Our study demonstrates an association between PADI4 and RA in
      the multiethnic population from South East Asia and suggests additional
      association with a PADI2 gene. The study thus provides further support for the
      notion that polymorphisms in genes for enzymes responsible for citrullination
      contribute to RA development in multiple populations of Asian descent.

PMID- 23164239
TI  - Tumorigenic potential of pituitary tumor transforming gene (PTTG) in vivo
      investigated using a transgenic mouse model, and effects of cross breeding with
      p53 (+/-) transgenic mice.
AB  - BACKGROUND: Pituitary tumor-transforming gene (PTTG) is an oncogene that is
      overexpressed in variety of tumors and exhibits characteristics of a transforming
      gene. Previous transgenic mouse models to access the tumorigenic potential in the
      pituitary and ovary have resulted in dysplasia without formation of visible
      tumors, possibly due to the insufficient expression of PTTG. PTTG expression
      level is critical for ovarian tumorigenesis in a xenograft model. Therefore, the
      tumorigenic function of PTTG in vivo remains unclear. We generated a transgenic
      mouse that overexpresses PTTG driven by the CMV promoter to determine whether
      PTTG functions as a transforming oncogene that is capable of initiating
      tumorigenesis. METHODS: Transgenic animals were generated by microinjection of
      PTTG transgene into the male pronucleus of FVB 0.5 day old embryos. Expression
      levels of PTTG in tissues of transgenic animals were analyzed using an
      immunohistochemical analysis. H&E staining and immunohistostaining were performed
      to examine the type of tumor in transgenic and PTTG transgenic/p53+/- animals.
      RESULTS: PTTG transgenic offspring (TgPTTG) were monitored for tumor development
      at various ages. H&E analysis was performed to identify the presence of cancer
      and hyperplastic conditions verified with the proliferation marker PCNA and the
      microvessel marker CD31. Immunohistochemistry was performed to determine
      transgene expression, revealing localization to the epithelium of the fallopian
      tube, with more generalized expression in the liver, lung, kidney, and spleen. At
      eight months of age, 2 out of 15 TgPTTG developed ovarian cancer, 2 out of 15
      developed benign tumors, 2 out of 15 developed cervical dysplasia, and 3 out of
      15 developed adenomyosis of the uterus. At ten months of age, 2 out of 10 TgPTTG
      developed adenocarcinoma of the ovary, 1 out of 10 developed a papillary serous
      adenocarcinoma, and 2 out of 10 presented with atypia of ovarian epithelial
      cells. Tumorigenesis is a multi-step process, often requiring multiple oncogenes
      and/or inactivation of tumor suppressor genes. Therefore, to understand the
      contribution of p53 to PTTG induced tumorigenesis, we crossbred TgPTTG to p53+/-
      mice and maintained those 8 to 10 months. TgPTTG/p53+/- animals developed
      sarcomas faster than p53+/- alone as well as different tumor types in addition to
      cervical carcinomas in situ in 10 out of 17 females. CONCLUSIONS: We conclude
      that while PTTG is a functional transforming oncogene, it requires an additional
      partner to effectively promote tumorigenesis through the loss of p53 include or
      between function or modulation.

PMID- 23164240
TI  - MicroRNA-203 up-regulates nitric oxide expression in temporomandibular joint
      chondrocytes via targeting TRPV4.
AB  - OBJECTIVE: MicroRNAs (miRNAs) are recognised as important regulators of a variety
      of fundamental biologic processes. Our study was undertaken to examine the role
      of MicroRNA-203 (miR-203) in modulating nitric oxide (NO) expression in female
      Sprague-Dawley rat mandibular condylar chondrocytes (MCCs) via targeting
      transient receptor potential vanilloid 4 (TRPV4) and to demonstrate the possible
      mechanism of NO inhibition by chondroprotective factor 17beta-oestradiol (E2).
      METHODS: The expression of TRPV4 in mandibular condylar cartilage tissue and MCCs
      was detected by immunohistochemistry, immunofluorescence (IF), RT-PCR and Western
      blot, respectively. Primary SD rat MCCs were exposed to lipopolysaccharide (LPS),
      plus Ruthenium Red, 4alpha-phorbol 12,13-didecanoate (4alphaPDD), over-expressed
      miR-203 or E2 (10(-9) to 10(-6)M), the cellular supernatants were used for NO
      assay, miR-203 levels were measured by quantitative RT-PCR while TRPV4 expression
      changes were analysed by Western blot. The dual luciferase activity assay was
      performed to identify the target gene of miR-203. RESULTS: TRPV4 and miR-203 were
      stably expressed in MCCs. The MCCs' expression of NO evoked by LPS could be
      enhanced or depressed by Ruthenium Red or 4alphaPDD. The dual luciferase assay
      suggested that TRPV4 was the direct target gene of miR-203. Over-expression of
      miR-203 inhibited the expression of TRPV4 and increased NO expression in MCCs. E2
      inhibited NO expression by inhibition of miR-203, which was concurrent with the
      up-regulation of TRPV4 expression level in MCCs. CONCLUSION: Our findings first
      suggested that miR-203 could up-regulate NO expression in female rat MCCs via
      targeting TRPV4. Moreover, the inhibition of NO by E2 might be at least in part
      through this mechanism.

PMID- 23164241
TI  - Computer assisted evaluation of retinal vessels tortuosity in Fabry disease.
AB  - PURPOSE: Fabry Disease (FD) is a rare X-linked metabolic disorder characterized
      by diffuse deposition of sphingolipids in many tissues. Retinal vessel tortuosity
      is a common ocular manifestation in FD and may represent a useful marker for the
      disease. Unfortunately its clinical evaluation is poorly reproducibile and
      alternative means of evaluation may be of interest. We tested a new semi
      automatic software measuring retinal vessel tortuosity from eye fundus digital
      images in a group of FD patients. METHODS: Observational case-control study
      evaluating four mathematical parameters describing tortuosity (relative length,
      sum of angle metric [SOAM], product of angle distance [PAD], triangular index)
      obtained from fundus pictures of 35 FD patients and 35 age-matched controls. Only
      the right eye was considered in order to reduce bias. Mann-Whitney test was used
      to compare the FD group versus the control group, males versus females and
      patients with versus without clinically identified retinal vessels tortuosity in
      the FD group. Linear regression analysis was performed on a subgroup of patients
      to evaluate the possible association of retinal vessels tortuosity parameters
      with age and with markers of systemic disease's progression. RESULTS: Three
      parameters (SOAM, PAD and triangular index) were significantly higher in FD
      patients in comparison with the controls (p < 0.0001, p = 0.001, p = 0.002
      respectively). In the FD group the same three parameters showed higher values in
      hemizygous males than in heterozygous females ((p < 0.0001, p = 0.002, p < 0.0001
      respectively). CONCLUSION: A computer assisted analysis of retinal vasculature
      demonstrated an increased vessels tortuosity in FD patients. The technique might
      be useful to establish disease severity and monitor its progression.

PMID- 23164242
TI  - What works to address prejudice? Look to developmental science research for the
      answer.
AB  - Developmental perspectives on prejudice provide a fundamental and important key
      to the puzzle for determining how to address prejudice. Research with
      historically disadvantaged and advantaged groups in childhood and adolescence
      reveals the complexity of social cognitive and moral judgments about prejudice,
      discrimination, bias, and exclusion. Children are aware of status and
      hierarchies, and often reject the status quo. Intervention, to be effective, must
      happen early in development, before prejudice and stereotypes are deeply
      entrenched.

PMID- 23164243
TI  - Cryopreservation increases DNA fragmentation in spermatozoa of smokers.
AB  - Smoking causes subfertility due to deterioration of spermatozoa including
      decreased concentration and abnormal morphology. Although evidence on the
      deleterious effects of smoking on spermatozoa parameters is well known, its
      interference with cryopreservation is not clear. This study aimed to investigate
      the effects of cryopreservation on sperm parameters and DNA fragmentation in non
      smokers and smokers. Semen samples were obtained from 40 normospermic male
      volunteers of whom 20 were non-smokers and 20 smokers. Samples were analyzed in
      terms of motility, concentration, morphology, and DNA fragmentation before
      freezing and 1 and 3 months after freezing and thawing. Ultrastructural
      alterations were investigated by transmission electron microscopy. Sperm
      morphology seemed to be more affected after cryopreservation in samples obtained
      from smokers. Ultrastructural examination showed alterations in the integrity of
      the membranes and increased subacrosomal swelling. Before freezing, the increase
      in DNA fragmentation rate in smokers was not statistically significant compared
      to that of non-smokers. However, after thawing, the DNA fragmentation rates were
      significantly high in both non-smokers and smokers compared to their respective
      rates before freezing. The extent of the increase in DNA fragmentation rate was
      significantly higher in smokers after thawing compared to that of non-smokers. In
      conclusion, cryopreservation causes alterations in membrane integrity and
      increases DNA fragmentation, thus triggering relatively negative effects on the
      sperm samples of smokers compared to that of non-smokers.

PMID- 23164245
TI  - Repression vs. activation of MOX, FMD, MPP1 and MAL1 promoters by sugars in
      Hansenula polymorpha: the outcome depends on cell's ability to phosphorylate
      sugar.
AB  - A high-throughput approach was used to assess the effect of mono- and
      disaccharides on MOX, FMD, MPP1 and MAL1 promoters in Hansenula polymorpha. Site
      specifically designed strains deficient for (1) hexokinase, (2) hexokinase and
      glucokinase, (3) maltose permease or (4) maltase were used as hosts for reporter
      plasmids in which beta-glucuronidase (Gus) expression was controlled by these
      promoters. The reporter strains were grown on agar plates containing varied
      carbon sources and Gus activity was measured in permeabilized cells on microtitre
      plates. We report that monosaccharides (glucose, fructose) repress studied
      promoters only if phosphorylated in the cell. Glucose-6-phosphate was proposed as
      a sugar repression signalling metabolite for H. polymorpha. Intriguingly, glucose
      and fructose strongly activated expression from these promoters in strains
      lacking both hexokinase and glucokinase, indicating that unphosphorylated
      monosaccharides have promoter-derepressing effect. We also show that maltose and
      sucrose must be internalized and split into monosaccharides to exert repression
      on MOX promoter. We demonstrate that at yeast growth on glucose-containing agar
      medium, glucose-limitation is rapidly created that promotes derepression of
      methanol-specific promoters and that derepression is specifically enhanced in
      hexokinase-negative strain. We recommend double kinase-negative and hexokinase
      negative mutants as hosts for heterologous protein production from MOX and FMD
      promoters.

PMID- 23164246
TI  - Cathodoluminescence microanalysis of irradiated microcrystalline and
      nanocrystalline samarium doped BaFCl.
AB  - BaFCl:Sm3+ is an efficient photoluminescent storage phosphor for ionizing
      radiation. Cathodoluminescence (CL) microanalysis enables the Sm2+ and Sm3+
      oxidation states of samarium doped BaFCl to be easily identified, provides
      information about electron-beam and X-ray induced modification of BaFCl:Sm, and
      enables the synthesis dependent spatial distribution of samarium dopants of <100
      ppm concentration to be determined with sub-100 nm resolution at 295 K. CL
      spectroscopy of BaFCl:Sm particles reveals broad CL emissions at ~ 360 and ~500
      nm associated with V k (Cl-) and oxygen-vacancy defects in the BaFCl host lattice
      and fine structure CL emissions associated with major 4GJ -> 6HJ (Sm3+) and 5DJ 
      > 7FJ (Sm2+) transitions. CL microanalysis shows samarium dopants are uniformly
      distributed in conventional sintered microcrystalline BaFCl:Sm. In contrast, CL
      investigations reveal that for BaFCl:Sm nanoparticles, which have been prepared
      using a co-precipitation method, with greatly improved Sm3+ -> Sm2+ conversion
      efficiency, the samarium dopants are concentrated near the particle surface
      resulting in a BaFCl:Sm3+ shell surrounding the BaFCl core, which is stable to
      energetic irradiation.

PMID- 23164244
TI  - Managing symptoms during cancer treatments: evaluating the implementation of
      evidence-informed remote support protocols.
AB  - BACKGROUND: Management of cancer treatment-related symptoms is an important
      safety issue given that symptoms can become life-threatening and often occur when
      patients are at home. With funding from the Canadian Partnership Against Cancer,
      a pan-Canadian steering committee was established with representation from eight
      provinces to develop symptom protocols using a rigorous methodology (CAN
      IMPLEMENT(c)). Each protocol is based on a systematic review of the literature to
      identify relevant clinical practice guidelines. Protocols were validated by
      cancer nurses from across Canada. The aim of this study is to build an effective
      and sustainable approach for implementing evidence-informed protocols for nurses
      to use when providing remote symptom assessment, triage, and guidance in self
      management for patients experiencing symptoms while undergoing cancer treatments.
      METHODS: A prospective mixed-methods study design will be used. Guided by the
      Knowledge to Action Framework, the study will involve (a) establishing an
      advisory knowledge user team in each of three targeted settings; (b) assessing
      factors influencing nurses' use of protocols using interviews/focus groups and a
      standardized survey instrument; (c) adapting protocols for local use, ensuring
      fidelity of the content; (d) selecting intervention strategies to overcome known
      barriers and implementing the protocols; (e) conducting think-aloud usability
      testing; (f) evaluating protocol use and outcomes by conducting an audit of 100
      randomly selected charts at each of the three settings; and (g) assessing
      satisfaction with remote support using symptom protocols and change in nurses'
      barriers to use using survey instruments. The primary outcome is sustained use of
      the protocols, defined as use in 75% of the calls. Descriptive analysis will be
      conducted for the barriers, use of protocols, and chart audit outcomes. Content
      analysis will be conducted on interviews/focus groups and usability testing with
      comparisons across settings. DISCUSSION: Given the importance of patient safety,
      patient-centered care, and delivery of quality services, learning how to
      effectively implement evidence-informed symptom protocols in oncology healthcare
      services is essential for ensuring safe, consistent, and effective care for
      individuals with cancer. This study is likely to have a significant contribution
      to the delivery of remote oncology services, as well as influence symptom
      management by patients at home.

PMID- 23164247
TI  - Schistosomiasis transmission and environmental change: a spatio-temporal analysis
      in Porto de Galinhas, Pernambuco--Brazil.
AB  - BACKGROUND: In Brazil, schistosomiasis mansoni infection is an endemic disease
      that mainly affects the country's rural populations who carry out domestic and
      social activities in rivers and water accumulations that provide shelter for the
      snails of the disease. The process of rural migration to urban centers and the
      disorderly occupation of natural environments by these populations from endemic
      areas have favored expansion of schistosomiasis to locations that had been
      considered to be disease-free. Based on environmental changes that have occurred
      in consequent to an occupation and urbanization process in the locality of Porto
      de Galinhas, the present study sought to identify the relationship between those
      chances, measure by remote-sensing techniques, and establish a new endemic area
      for schistosomiasis on the coast of Pernambuco State--Brazil. METHODS: To gather
      prevalence data, two parasitological census surveys were conducted (2000 and
      2010) using the Kato-Katz technique. Two malacological surveys were also
      conducted in the same years in order to define the density and infection rate of
      the intermediate host. Based on these data, spatial analyses were done, resulting
      in maps of the risk of disease transmission. To ascertain the environmental
      changes that have occurred at the locality, images from the QuickBird satellite
      were analyzed, thus resulting in land use maps. RESULTS: Over this 10-year
      period, the foci of schistosomiasis became more concentrated in the Salinas
      district. This area was considered to be at the greatest risk of schistosomiasis
      transmission and had the highest prevalence rates over this period. The study
      illustrated that this was the area most affected by the environmental changes
      resulting from the disorderly urbanization process, which gave rise to unsanitary
      environments that favored the establishment and maintenance of foci of
      schistosomiasis transmission, thereby consolidating the process of expansion and
      endemization of this parasitosis.

PMID- 23164248
TI  - Editorial: minority ethnic older people in nursing homes: meaning, purpose and
      well-being.

PMID- 23164249
TI  - Editorial: the role of the nurse in long-term care.

PMID- 23164250
TI  - Appreciating the 'person' in long-term care.
AB  - BACKGROUND: Internationally, approaches to the long-term care of older people are
      changing. New models are being developed that aim to de-institutionalise care
      settings, maximise opportunities for older people to participate in decision
      making and move from a predominant medical model of care to one that is community
      orientated. AIMS: The aim of this study is to highlight similarities and
      differences between the different models that exist and explore the implications
      of these for the role of the registered nurse in long-term care. METHODS: We
      chose three models for review as these represent a range of views of person
      centredness, each having distinct roots and focus. The models chosen were as
      follows: (i) culture change, (ii) person-centred practice and (iii) relationship
      centred care. RESULTS: The review highlights two key issues - (i) the
      distinctiveness of different models and frameworks and (ii) different
      interpretations of 'person'. Firstly, we identify a disconnection between
      espoused differences between models and frameworks and the reality of these
      differences. The evidence also identifies how some models and frameworks adopt a
      more inclusive conceptualisation of person and personhood and do not define
      personhood in relation to role (resident, nurse and family member). CONCLUSIONS:
      There is merit in the development of models and frameworks that try to make
      explicit the different dimensions of person centredness in long-term care.
      However, the focus on the development of these, without sufficient attention
      being paid to evidence of best practices grounded in the concept of personhood,
      person-centred care is in danger of losing its original humanistic emphasis.
      Further, models and frameworks need to take account of the personhood of all
      persons. IMPLICATIONS FOR PRACTICE: Registered nurses need to have an
      understanding of the concept of personhood to make sense of the various person
      centred practice frameworks that exist. Without this understanding, there is a
      danger that the essence of personhood may be lost in the zeal to implement
      particular models and frameworks.

PMID- 23164251
TI  - Supporting and promoting personhood in long term care settings: contextual
      factors.
AB  - The need for personhood-focused long-term care (LTC) is well-documented. A myriad
      of sociocultural, political, nursing/professional and organisational contexts
      facilitate or hinder registered nurses (RNs)' capacity to ensure personhood
      focused LTC. Complexities derive from the countless interrelated aspects of these
      contexts, blurring clear distinctions of causality, responsibility and
      accountability. Context-related complexities were highlighted at a recent
      international conference attended by invited experts in LTC leadership from six
      countries (Canada, USA, England, Northern Ireland, New Zealand and Sweden). The
      group was convened to explore the value and contributions of RNs in LTC
      (McGilton, , International Journal of Older People Nursing 7, 282). The purpose
      of this paper is to expand the discussion of personhood-focused care beyond RNs,
      to contexts that influence the RN's capacity to ensure personhood-focused
      practices are embedded in LTC settings. Consistent with key topics covered at the
      international conference, we selected four major contexts for discussion in this
      paper: (i) sociocultural, (ii) public policy/financing/regulation, (iii)
      nursing/professional and (iv) organisational. For each context, we provide a
      brief description, literature and examples from a few countries attending the
      conference, potential impact on personhood-focused practices and RN strategies to
      facilitate personhood-focused care. The knowledge gained from attending to the
      influence of contextual factors on the RN's role in facilitating personhood
      focused practices provides critical insights and directions for interventions
      aimed to maximise RN role effectiveness in LTC. In practice, understanding
      linkages between the various contexts offers indispensable insight for LTC nurse
      leaders charged with managing day-to-day operations and leading quality
      improvement initiatives that promote personhood-focused practices.

PMID- 23164252
TI  - Moving the agenda forward: a person-centred framework in long-term care.
AB  - BACKGROUND: Internationally, the role of the registered nurse (RN) in long-term
      care (LTC) settings has evolved in response to the demands of governmental and
      organisational priorities. In stark contrast to the regulatory mandates, a person
      centred care approach in LTC settings would require different outcomes, processes
      and competencies of the RN. AIMS: This article explores the implications of
      defining the RN's role in delivering person-centred care in LTC homes. METHODS:
      Based on a review of the literature, we present a framework that can be used to
      gather evidence on the outcomes, processes of care and competencies required of
      RNs to lead their teams to person-centred LTC homes. RESULTS: The development of
      the framework highlighted several issues: (i) current measures of quality in LTC
      settings focus on health outcomes and avoiding adverse events rather than on
      resident quality of life and well-being, which influences the RN's practice; (ii)
      person-centred care has emerged as a focus of care, yet measures currently
      developed are limited, and thus, new outcomes are proposed; (iii) to practice in
      a person-centred way, RNs must work through others on their team to ensure that
      staff truly relate to their residents, tailor approaches based on the remaining
      abilities of the residents and manipulate environments to match the competence of
      the individual, while focusing on residents' personhood and (iv) competencies of
      RNs to deliver person-centred care include leadership, facilitation, clinical
      excellence and critical thinking skills. CONCLUSIONS: RNs need to be supported,
      allowed and encouraged in redesigning their role, to work to their full capacity
      if they are truly to support person-centred care in LTC settings.

PMID- 23164253
TI  - Traditional prejudice remains outside of the WEIRD world.
AB  - Dixon et al. accurately describe subtle mechanisms of discrimination that inhibit
      minorities' collective action in modern democratic societies. This commentary
      suggests that in contemporary non-Western societies, where ethnic conflicts are
      more violent, traditional overt forms of prejudice still exist and predict
      discrimination of ethnic and racial minorities. Thus, prejudice reduction models
      should and do improve intergroup relations in such contexts.

PMID- 23164254
TI  - Strategies towards sequencing complex crop genomes.
AB  - A report on the Strategies for de novo assemblies of complex crop genomes
      workshop held at The Genome Analysis Centre, Norwich, UK, 8-10 October 2012. 

PMID- 23164255
TI  - Effects of oxymatrine on the neuropathic pain induced by chronic constriction
      injury in mice.

PMID- 23164256
TI  - Comparison of polymorphonuclear- and lymphocyte-rich tuberculous pleural
      effusions.
AB  - SETTING: Most patients with tuberculous pleural effusions (TPE) have more than
      50% lymphocytes in the pleural fluid. Data on patients in whom polymorphonuclear
      leukocytes (PMNLs) are the predominant cell type are scarce. OBJECTIVE: To
      compare the clinical, biochemical, microbiological  and radiological
      characteristics between patients with predominantly PMNL and those with
      lymphocytic TPE. DESIGN: Retrospective analysis of 214 consecutive patients with
      TPE. RESULTS: The pleural fluid was PMNL-rich in 24 (11%) cases at the time of
      first thoracocentesis. Compared with  those whose pleural fluid was predominantly
      lymphocytic, these patients showed a higher yield of mycobacteria in culture of
      sputum (50% vs. 25%, P = 0.03) and pleural fluid (50% vs. 10%, P < 0.01) on solid
      media, as well as higher pleural adenosine deaminase (ADA) levels (80  vs. 62
      U/l, P = 0.02) at the expense of both ADA1 and ADA2 isoenzymes. A shift towards
      pleural lymphocytic predominance was observed in more than half of the PMNL
      predominant patients subjected to repeat thoracocentesis. CONCLUSIONS: The
      finding of a predominantly PMNL exudate should  not rule out TPE, particularly
      when pleural ADA activity is elevated. The collection of sputum and pleural fluid
      samples for mycobacterial culture should be encouraged in the case of suspected
      PMNL-rich TPE, as they are frequently positive in this early stage.

PMID- 23164257
TI  - A case of simultaneous anterior and inferior ST-segment elevation myocardial
      infarction due to isolated occlusion of a wrapped right posterior descending
      artery.
AB  - We present a case of a 72-year-old man with acute coronary syndrome due to
      isolated acute occlusion of a wrapped right posterior descending artery.
      Electrocardiogram showed simultaneous anterior and inferior ST-segment
      elevations. We discuss the causes of this exceptional electrocardiographic
      pattern.

PMID- 23164258
TI  - Clinical correlates of early repolarization and J wave patterns...are they
      proarrhythmic on their own?

PMID- 23164259
TI  - Statistical learning and prejudice.
AB  - Human behavior is guided by evolutionarily shaped brain mechanisms that make
      statistical predictions based on limited information. Such mechanisms are
      important for facilitating interpersonal relationships, avoiding dangers, and
      seizing opportunities in social interaction. We thus suggest that it is essential
      for analyses of prejudice and prejudice reduction to take the predictive accuracy
      and adaptivity of the studied prejudices into account.

PMID- 23164260
TI  - Correcting and interpreting the effect of cognitive therapy versus exposure in
      anxiety disorders.
AB  - Dr. Ougrin's evaluation of cognitive therapy versus exposure in anxiety disorders
      reported a standardised mean difference [SMD] (95% confidence interval [CI]) of
      0.52 (0.37, 0.74) for short-term outcomes and 0.46 (0.29, 0.73) for long-term
      outcomes in social phobia, and 0.88 (0.69, 1.11) for short-term outcomes and 1.05
      (0.80, 1.37) for long-term outcomes in posttraumatic stress disorder (PTSD).
      These were incorrectly meta-analysed. Upon re-analysis, we found that the correct
      SMD (95% CI) was -0.66 (-1.19, -0.14) for short-term outcomes and mean difference
      (95% CI) of -29.66 (-46.13, -13.19) on the Social Phobia subscale from the Social
      Phobia Anxiety Inventory for long-term outcomes in Social Phobia. For PTSD, the
      SMD (95% CI) for short-term outcomes was -0.13 (-0.36, 0.11) and 0.05 (-0.22,
      0.32) for long-term outcomes. However, correcting the errors did not change the
      interpretation of the findings considerably.

PMID- 23164263
TI  - Update on editorial policy for contributions to Clinical Otolaryngology.

PMID- 23164264
TI  - Controversies in the specialist management of adult epistaxis:  an evidence-based
      review.

PMID- 23164265
TI  - Exercise interventions on health-related quality of life for people with cancer
      during active treatment.

PMID- 23164266
TI  - Exercise interventions on health-related quality of life for cancer survivors.

PMID- 23164267
TI  - Glottal insufficiency with thyroid cartilage implantation: our experience in
      eight patients.

PMID- 23164268
TI  - Inter-observer reliability of operative supervision coding by forty three ENT
      surgeons of twenty eight operations.

PMID- 23164269
TI  - Reconstruction of congenital inverted conchal bowl deformity: our experience in
      two of four children.

PMID- 23164270
TI  - Post-tonsillectomy pain in 24 children - utilising short message service (SMS) to
      assess postoperative outcomes.

PMID- 23164271
TI  - Preformed homologous cortical bone prostheses for ossiculoplasty: preliminary
      clinical results in eighteen patients.

PMID- 23164272
TI  - Re: the effects of disclosure of sequential rhinomanometry scores on post
      septoplasty subject scores of nasal obstruction: a randomised controlled trial.

PMID- 23164276
TI  - Re: who will have the 'guts' to quantify the decline in surgical skills of older
      surgeons? A commentary on the paper that shows that this occurs in thyroid
      surgeons.

PMID- 23164274
TI  - Re: who will have the 'guts' to quantify the decline in surgical skills of older
      surgeons? A commentary on the paper that shows that this occurs in thyroid
      surgeons.

PMID- 23164278
TI  - Reducing treatment delay by improving information flow within the
      multidisciplinary team: a muticycle audit spiral in head and neck cancer.

PMID- 23164279
TI  - A pilot randomised control trial: the effects of decaffeinated drinks on voice
      quality.

PMID- 23164280
TI  - The holistic approach--the only way to go.

PMID- 23164281
TI  - A study of cathodoluminescence and trace element compositional zoning in natural
      quartz from volcanic rocks: mapping titanium content in quartz.
AB  - This article concerns application of cathodoluminescence (CL) spectroscopy to
      volcanic quartz and its utility in assessing variation in trace quantities of Ti
      within individual crystals. CL spectroscopy provides useful details of intragrain
      compositional variability and structure but generally limited quantitative
      information on element abundances. Microbeam analysis can provide such
      information but is time-consuming and costly, particularly if large numbers of
      analyses are required. To maximize advantages of both approaches, natural and
      synthetic quartz crystals were studied using high-resolution hyperspectral CL
      imaging (1.2-5.0 eV range) combined with analysis via laser ablation inductively
      coupled plasma mass spectrometry (LA-ICPMS). Spectral intensities can be
      deconvolved into three principal contributions (1.93, 2.19, and 2.72 eV), for
      which intensity of the latter peak was found to correlate directly with Ti
      concentration. Quantitative maps of Ti variation can be produced by calibration
      of the CL spectral data against relatively few analytical points. Such maps
      provide useful information concerning intragrain zoning or heterogeneity of Ti
      contents with the sensitivity of LA-ICPMS analysis and spatial resolution of
      electron microprobe analysis.

PMID- 23164282
TI  - Definitive radiotherapy for early (T1-T2) glottic squamous cell carcinoma: a 20
      year Cleveland Clinic experience.
AB  - PURPOSE: To report our 20 yr experience of definitive radiotherapy for early
      glottic squamous cell carcinoma (SCC). METHODS AND MATERIALS: Radiation records
      of 141 patients were retrospectively evaluated for patient, tumor, and treatment
      characteristics. Cox proportional hazard models were used to perform univariate
      (UVA) and multivariate analyses (MVA). Cause specific survival (CSS) and overall
      survival (OS) were plotted using cumulative incidence and Kaplan-Meir curves,
      respectively. RESULTS: Of the 91% patients that presented with impaired voice,
      73% noted significant improvement. Chronic laryngeal edema and dysphagia were
      noted in 18% and 7%, respectively. The five year LC was 94% (T1a), 83% (T1b), 87%
      (T2a), 65% (T2b); the ten year LC was 89% (T1a), 83% (T1b), 87% (T2a), and 53%
      (T2b). The cumulative incidence of death due to larynx cancer at 10 yrs was 5.5%,
      respectively. On MVA, T-stage, heavy alcohol consumption during treatment, and
      used of weighted fields were predictive for poor outcome (p < 0.05). The five
      year CSS and OS was 95.9% and 76.8%, respectively. CONCLUSIONS: Definitive
      radiotherapy provides excellent LC and CSS for early glottis carcinoma, with
      excellent voice preservation and minimal long term toxicity. Alternative
      management strategies should be pursued for T2b glottis carcinomas.

PMID- 23164283
TI  - The genetic regulation of the terminating phase of liver regeneration.
AB  - BACKGROUND: After partial hepatectomy (PHx), the liver regeneration process
      terminates when the normal liver-mass/body-weight ratio of 2.5% has been re
      established. To investigate the genetic regulation of the terminating phase of
      liver regeneration, we performed a 60% PHx in a porcine model. Liver biopsies
      were taken at the time of resection, after three weeks and upon termination the
      sixth week. Gene expression profiles were obtained using porcine oligonucleotide
      microarrays. Our study reveals the interactions between genes regulating the cell
      cycle, apoptosis and angiogenesis, and the role of Transforming Growth Factor
      beta (TGF-beta) signalling towards the end of liver regeneration. RESULTS:
      Microarray analysis revealed a dominance of genes regulating apoptosis towards
      the end of regeneration. Caspase Recruitment Domain-Containing Protein 11
      (CARD11) was up-regulated six weeks after PHx, suggesting the involvement of the
      caspase system at this time. Zinc Finger Protein (ZNF490) gene, with a potential
      negative effect on cell cycle progression, was only up-regulated at three and six
      weeks after PHx indicating a central role at this time. TGF-beta regulation was
      not found to be significantly affected in the terminating phase of liver
      regeneration. Vasohibin 2 (VASH2) was down-regulated towards the end of
      regeneration, and may indicate a role in preventing a continued vascularization
      process. CONCLUSIONS: CARD11, ZNF490 and VASH2 are differentially expressed in
      the termination phase of liver regeneration. The lack of TGF-beta up-regulation
      suggests that signalling by TGF-beta is not required for termination of liver
      regeneration.

PMID- 23164284
TI  - Liking more or hating less? A modest defence of intergroup contact theory.
AB  - Here, I argue that Dixon et al. have overstated the prevalence of "benevolent"
      forms of prejudice; many stigmatised groups are currently the targets of overtly
      hostile evaluation and treatment by others (e.g., Muslims; immigrant groups). I
      also believe that the target article oversimplifies its presentation of prejudice
      researchers' primary theoretical and policy goals and that it overlooks important
      work in intergroup emotions.

PMID- 23164285
TI  - Poly-SNO-HSA: a safe and effective multifunctional antitumor agent.

PMID- 23164286
TI  - The development of social learning in interactive and observational contexts.
AB  - From the first year of life, imitative learning readily occurs in contexts where
      a demonstrator directly interacts with infants (i.e., "interactive contexts"),
      and at least by 18 months, imitation will also occur in third-party or
      observational contexts where infants witness a demonstration by another person
      that is not directed at them. However, it remains unclear whether imitation is
      differentially facilitated in these two contexts in young children. In the
      current experiment, we tested both imitation and emulation learning in younger
      (18 months) and older (24 months) infants in three different social learning
      conditions: interactive, social observational, and solitary observational. We
      found that the younger group imitated novel actions more after interactive
      demonstration than after solitary observational demonstration; older infants
      imitated equally in all conditions. Emulation occurred equally in all conditions
      for the younger group, but the older group emulated significantly less in the
      interactive condition than in the solitary observational condition. Furthermore,
      we found that mirror self-recognition was related to imitation in the solitary
      observational condition. These results suggest that imitation is initially
      facilitated by direct interaction but that by the end of the second year can
      occur just as easily in noninteractive contexts. This change may be dependent on
      developments in social cognition, in particular, the understanding of self-other
      equivalence.

PMID- 23164287
TI  - Faustian bargains for minorities within group-based hierarchies.
AB  - A dual-audience signaling problem framework provides a deeper understanding of
      the perpetuation of group-based inequality. We describe a model of
      underachievement among minority youth that posits a necessary trade-off between
      academic success and peer social support that creates a dilemma not typically
      encountered by nonminorities. Preliminary evidence consistent with the approach
      is discussed. Such strategic agent perspectives complement the psychological
      approach put forth by Dixon et al., but with minimal ancillary assumptions.

PMID- 23164288
TI  - International plant molecular biology: a bright future for green science.
AB  - A report on the 10th International Congress of Plant Molecular Biology, Jeju,
      South Korea, October 21-26, 2012. 

PMID- 23164290
TI  - Endoscopic stapes surgery: our experience in thirty two patients.

PMID- 23164289
TI  - Correlates of STI symptoms among female sex workers with truck driver clients in
      two Mexican border towns.
AB  - BACKGROUND: Female sex workers (FSW) are at increased risk for HIV and other STI
      due to occupation-related risks and exposures. Long-distance truck drivers have
      been implicated in the spread of HIV, but less is known about HIV/STI risks of
      FSW servicing truck drivers, especially in North America. As part of an
      international collaborative pilot study, we interviewed FSWs servicing truck
      driver clients along two major transportation corridors to explore factors
      associated with recent STI symptoms. METHODS: A cross-sectional study of 200 FSW
      was conducted in Mexico: 100 from Nuevo Laredo (U.S. border); 100 from Ciudad
      Hidalgo (Guatemalan border). Eligibility criteria included age >=18 years,
      speaking English or Spanish, and having >=1 truck driver client in the past
      month. The main outcome was reporting any recent STI symptoms, defined as
      experiencing genital/anal warts, genital ulcers/sores, genital itching, or
      abnormal vaginal discharge in the past 6 months. Logistic regression was used to
      identify correlates of recent STI symptoms. RESULTS: Median age of FSW was 29
      years, 74% were single, 87% had <9th grade education, and median income was 4000
      pesos/month ($300 USD). Sex work occurred at a bar/cantina for 70%. One-quarter
      had never been tested for HIV, 53% reported lifetime drug use, 22% reported
      drinking alcohol before/during transactional sex and 17% reported recent STI
      symptoms. After controlling for age and study site, factors associated with STI
      symptoms were lifetime drug use (AOR 2.9, 95% CI 1.2-6.9), drug use before/during
      sex (AOR 2.8, 95% CI 1.1-7.1), alcohol use before/during sex (AOR 5.2, 95% CI
      2.2, 12.6), forced sex ever (AOR 2.6, 95% CI 1.1-6.1), lifetime history of arrest
      (AOR 2.3, 95% CI 1.0-5.0), and being surveyed in Nuevo Laredo rather than Ciudad
      Hidalgo (AOR 4.8, 95% CI 2.0-10.0). CONCLUSIONS: The associations we observed
      between recent STI symptoms and drug and alcohol use suggest that interventions
      are needed that promote consistent and effective safer sex practices, especially
      while under the influence of alcohol or other substances.

PMID- 23164291
TI  - Nanomorphology of P3HT:PCBM-based absorber layers of organic solar cells after
      different processing conditions analyzed by low-energy scanning transmission
      electron microscopy.
AB  - In this study the nanomorphology of P3HT:PC61BM absorber layers of organic solar
      cells was studied as a function of the processing parameters and for P3HT with
      different molecular weight. For this purpose we apply scanning transmission
      electron microscopy (STEM) at low electron energies in a scanning electron
      microscope. This method exhibits sensitive material contrast in the high-angle
      annular dark-field (HAADF) mode, which is well suited to distinguish materials
      with similar densities and mean atomic numbers. The images taken with low-energy
      HAADF STEM are compared with conventional transmission electron microscopy and
      atomic force microscopy images to illustrate the capabilities of the different
      techniques. For the interpretation of the low-energy HAADF STEM images, a
      semiempirical equation is used to calculate the image intensities. The
      experiments show that the nanomorphology of the P3HT:PC61BM blends depends
      strongly on the molecular weight of the P3HT. Low-molecular-weight P3HT forms rod
      like domains during annealing. In contrast, only small globular features are
      visible in samples containing high-molecular-weight P3HT, which do not change
      significantly after annealing at 150 degrees C up to 30 min.

PMID- 23164292
TI  - Overweight and blood pressure: high time for action.

PMID- 23164293
TI  - The elephant moves into the sunlight: progress in childhood malnutrition.
AB  - Beginning with a historical summary of investigative work into protein-energy
      malnutrition, now termed 'severe acute malnutrition', this review ends by
      summarizing recent initiatives to tackle the global problem of malnutrition,
      specifically Scaling-Up Nutrition (SUN). In  early years, macronutrient
      deficiency or imbalance was considered the principal cause of complex metabolic
      disturbances, including kwashiorkor, whereas, now, micronutrient deficiency
      infections, including HIV, and a background of deprivation are implicated.
      Different approaches to management  are reviewed. The rehabilitation of
      individual children by protocolised-phased feeding has largely given way to
      community-based therapeutic feeding. Despite sporadic successes, the overall
      impact on morbidity and mortality has been so disappointing that the global
      community now plans a new  initiative, viz. SUN. Its focus on the critical window
      of 1000 days (from conception to 2 years) is similar to the earlier focus on
      early childhood vulnerability which inspired the under-5 clinics and their
      integration into maternal and child health programmes. 'Targeted'  interventions,
      recently more prominent than integrated community-based primary care, often
      undertaken by NGOs, have been effective, although sometimes imperfectly
      accountable. Will SUN, aiming for a broad approach, and the participation of
      recipient communities finally succeed in integrating  nutrition into child
      health?

PMID- 23164294
TI  - High prevalence of hypertension in obese children in the Caribbean.
AB  - BACKGROUND: The prevalence of obesity is increasing worldwide. Obesity in
      children and adults leads to diabetes mellitus type 2 and cardiovascular disease.
      AIM: To determine the prevalence of high blood pressure in overweight and obese
      children in the Caribbean. METHODS: In a cross-sectional study, weight and height
      were measured in all 5-16-year-old children attending public school in 2008 on
      Bonaire, an island in the Caribbean. Cut-off values for body mass index (BMI) are
      defined by the International Obesity Task Force. Blood pressure was measured in
      all overweight and obese children as well as in a control group with normal
      weight and compared with reference values from the National High Blood Pressure
      Working Group on Children. RESULTS: 94% (2023/2152) of all children participated
      in the study. 17% (335/2023) of the children were overweight (excluding obesity)
      and a further 12% (246/2023) were obese. Hypertension was found in 13% (67/526)
      of children of normal weight, in 23% (71/307) of overweight children and in 53%
      (127/242) of obese children. Compared with normal-weight children, the odds for
      hypertension were 2.1 (95% CI 1.4-3.0) for overweight children and 7.2 (95% CI
      5.0-10.3) for obese children. CONCLUSION: There is a high prevalence of
      hypertension in overweight and obese children on Bonaire. As hypertension is a
      harbinger of cardiovascular disease, early detection and treatment of overweight
      and obese children is of paramount importance and their blood pressure needs to
      be measured regularly.

PMID- 23164295
TI  - Prevalence of hypertension in primary school-children in Port Harcourt, Nigeria.
AB  - BACKGROUND: Hypertension is defined as average systolic and/or diastolic blood
      pressure (BP) >=95th per centile for gender, age and height, and pre-hypertension
      as >=90th and <95th per centile, measured on three occasions. Although the
      prevalence of hypertension during  childhood is lower than that in adulthood, it
      is not rare in children. AIMS AND OBJECTIVES: To evaluate the prevalence of
      hypertension and its severity in primary school-children in Port Harcourt.
      METHODS: A stratified, multi-staged sampling technique was used to recruit 
      pupils between 6 and 12 years of age in 13 primary schools. Data were collected
      using a pre-tested questionnaire completed by parents/guardians. The average of
      three blood pressure measurements was taken for each pupil using standardized
      techniques. RESULTS: A total of 1302 pupils  of whom 585 (44.9%) males and 717
      (55.1%) females were studied, giving a male to female ratio of 1:1.2. The
      prevalence of hypertension was 61 (4.7%), 55 (4.2%) with stage 1 and six (0.5%)
      with stage 2 hypertension. Sixty (4.6%) of the pupils  had pre-hypertension.
      Twenty-three (3.9%) of the 585 males and 38 (5.3%) of the 717 females were
      hypertensive (P = 0.25). The mean (SD) age of 8.83 (1.90) years for the
      normotensive children was higher than the mean (SD) age of 8.56  (2.05) years for
      the hypertensive children (P = 0.27). Of the study subjects, 152 (11.7%) were
      underweight, 998 (76.7%) were of normal weight, 75 (5.7%) were overweight and 77
      (5.9%) were obese. The prevalence of hypertension among  the different weight
      groups fell steadily from 13 (16.9%) in the obese children to 4 (5.3%) in the
      overweight children, to 43 (4.3%) in the normal weight children and one (0.7%) in
      the underweight children (P<0.001). CONCLUSION: The prevalence  of hypertension
      in school-children in Port Harcourt is 4.7% which is similar to that in other
      studies in Nigeria and elsewhere. A higher BMI was significantly associated with
      a higher prevalence of hypertension.

PMID- 23164296
TI  - Distribution of haematological and chemical pathology values among infants in
      Malawi and Uganda.
AB  - BACKGROUND: Data on paediatric reference laboratory values are limited for sub
      Saharan Africa. OBJECTIVE: To describe the distribution of haematological and
      chemical pathology values among healthy infants from Malawi and Uganda. METHODS:
      A cross-sectional study was  conducted among healthy infants, 0-6 months old,
      born to HIV-uninfected mothers recruited from two settings in Blantyre, Malawi
      and Kampala, Uganda. Chemical pathology and haematology parameters were
      determined using standard methods on blood samples. Descriptive analyses by age
      group  were performed based on 2004 Division of AIDS Toxicity Table age
      categories. Mean values and interquartile ranges were compared by site and age
      group. RESULTS: A total of 541 infants were included altogether, 294 from Malawi
      and 247 from Uganda. Overall, the mean laboratory values  were comparable between
      the two sites. Mean alkaline phosphatase levels were lower among infants aged
      <=21 days while aspartate aminotransferase, creatinine, total bilirubin and gamma
      glutamyl transferase were higher in those aged 0-7 days than in older infants.
      Mean haematocrit,  haemoglobin and neutrophil counts were higher in the younger
      age-groups (<35 days) and overall were lower than US norms. Red and white blood
      cell counts tended to decrease after birth but increased after ~2 months of age.
      Mean basophil counts were higher in Malawi than in Uganda in  infants aged 0-1
      and 2-7 days; mean counts for eosinophils (for age groups 8-21 or older) and
      platelets (for all age groups) were higher in Ugandan than in Malawian infants.
      Absolute lymphocyte counts increased with infant age. CONCLUSION: The chemical
      pathology  and haematological values in healthy infants born to HIV-uninfected
      mothers were comparable in Malawi and Uganda and can serve as useful reference
      values in these settings.

PMID- 23164297
TI  - Outcome of anti-retroviral treatment in HIV-infected orphans and non-orphans at
      an ART centre in North India.
AB  - BACKGROUND: Few Indian studies have reported the long-term efficacy of anti
      retroviral treatment (ART) in children and in orphaned, HIV-infected children in
      particular. AIM: To study differences in outcome of ART in HIV-infected orphans
      compared with non-orphans. METHODS: A retrospective study of 87 HIV-infected
      children who commenced ART in the period January 2006 to August 2007. The main
      measures were orphan status, absolute CD4 count and weight-for-height (WHZ) and
      height-for-age (HAZ) Z-scores. RESULTS: Median follow-up was 33 months. Forty 
      (45.9%) children were orphaned. Orphans and non-orphans had similar baseline
      median WHZ and HAZ (-2.48 vs -2.63, P = 0.65 and -2.78 vs -2.91, P = 0.77,
      respectively). The  two groups were similar in terms of WHO clinical stage and
      frequency of severe immunosuppression at presentation (P = 0.88 and 0.25,
      respectively). After ART initiation, the median absolute CD4 count increased
      progressively in both groups. Median WHZ and HAZ  increased throughout the study
      period in the orphans and reached -1 at 27 and 39 months of ART, respectively. In
      the non-orphans, WHZ remained below that of the orphan group, the difference
      becoming statistically significant from 18 months of ART. The increment in HAZ in
      the non-orphan  group was at par with the orphan group until 12 months of follow
      up, after which it fell between 18 and 30 months. Subsequently, HAZ rose but
      remained below that of the orphan group. Both WHZ and HAZ failed to reach -1 in
      the non-orphan group. In both groups, 85% reported 100% adherence  to ART.
      CONCLUSION: The outcome of ART is not affected by orphan status with the extended
      family adequately supporting orphaned children. Growth of children whose parents
      are HIV-infected may be constrained despite ART if there is inadequate family
      support.

PMID- 23164298
TI  - Coverage of the vitamin A supplementation programme for child survival in Nepal:
      success and challenges.
AB  - BACKGROUND: Nepal's national vitamin A programme, which began in 1993 and
      continues twice yearly, targets pre-school-aged children in all districts of the
      country in an effort to reduce morbidity, mortality and nutritional blindness.
      OBJECTIVE: To characterize the coverage of the Nepal National Vitamin A Programme
      (NVAP) for pre-school-aged children in Nepal and to identify risk factors for
      failure to receive vitamin A supplementation. METHODS: The relationship between
      receipt of a vitamin A capsule and demographic and health indicators was examined
      in a cross-sectional study of 4013 children aged 12-59 months and their families
      who participated in the 2011 Nepal Demographic and Health Survey (NDHS), a
      nationally representative survey. Coverage of the vitamin A programme was
      compared with coverage estimates from surveys in 2001 and 2006. RESULTS: Coverage
      estimates of the national vitamin A programme for children aged 12-59 months as
      assessed by the 2001, 2006 and 2011 NDHS were 84.3%, 96.6% and 92.1%,
      respectively. Children who missed a vitamin A capsule were more likely to be
      younger and anaemic, have less educated parents, live in rural areas, and have
      higher child and infant mortality in the family. CONCLUSIONS: The national
      vitamin A supplementation programme in Nepal has relatively high coverage of
      children aged 12-59 months but still misses children in families with high child
      mortality. Further measures might be needed to sustain a high level of programme
      coverage.

PMID- 23164299
TI  - A premature neonate with early-onset neonatal sepsis owing to Brevundimonas
      vesicularis complicated by persistent meningitis and lymphadenopathy.
AB  - Human infection by Brevundimonas vesicularis is very rare, especially in
      children. A 29-week-old neonate is reported who developed early neonatal sepsis
      owing to B. vesicularis complicated by persistent meningitis and lymphadenopathy.
      B. vesicularis may be an emerging  pathogen in neonatal infection.

PMID- 23164300
TI  - Encephalitis following purified chick embryo rabies vaccination.
AB  - Encephalitis following purified chick embryo rabies vaccination is rare and only
      a few cases have been reported. A 6-year-old boy is reported who developed
      features consistent with encephalitis following a third dose of the vaccine and
      made a complete recovery.

PMID- 23164301
TI  - Acute appendicitis in two children with Henoch-Schonlein purpura.
AB  - In Henoch-Schonlein purpura (HSP), involvement of the ileum and ascending colon
      with vasculitis can mimic appendicitis and cause unnecessary appendicectomy. A 13
      year-old boy presented with signs of HSP and abdominal pain. He was treated with
      prednisolone (2 mg/kg/day) for  10 days, but there was no improvement. At
      laparotomy he had acute suppurative appendicitis. A 12-year-old girl presented
      with HSP associated with abdominal pain and bloody diarrhoea and at laparotomy
      was also found to have suppurative appendicitis. Both patients had vasculitic
      areas in the  ileum. In HSP, although suppurative appendicitis is rare, it should
      always be considered and appropriate investigations, including ultrasonography,
      undertaken.

PMID- 23164303
TI  - Pulp polyp in traumatized primary teeth--a case-control study.
AB  - AIM: To assess clinical characteristics and other factors associated with the
      occurrence of pulp polyp in traumatized primary teeth as well to evaluate the
      impact of pulp polyp occurrence on clinical decision-making after traumatic
      injuries. MATERIAL AND METHODS: This study was divided into three phases. First,
      occurrence and clinical characteristics of pulp polyp were assessed followed by a
      descriptive analysis and categorical tests of association. Secondly, a case
      control design was used, and the occurrence of pulp polyp was set as the outcome.
      In third phase, the occurrence of pulp polyp after fracture with pulp exposure
      was investigated as a variable possibly associated with clinical decision-making
      (dental extraction/endodontic treatment). Logistic regression analyses were used,
      and odds ratios and 95% confidence interval (OR; 95% CI) were calculated in
      second and third phases. RESULTS: Occurrence of pulp polyp in traumatized primary
      teeth was of 2.3%. Hyperplastic tissue color and proliferation size were not
      associated with the time to seek treatment after injury (P > 0.05). Children up
      to 2 years of age had more chance of having pulp polyp in comparison with older
      children (3.15; 1.15-8.64). Teeth with crown-root fracture had more chance of
      dental extraction in the therapeutic approach than the teeth with only crown
      fracture (4.36; 1.10-17.32). Presence of pulp polyp was not associated with the
      treatment carried out. CONCLUSIONS: Occurrence of pulp polyp in traumatized
      primary teeth is not frequent and is associated with the age when traumatic
      dental injury occurs but does not interfere directly with the therapeutic
      approach.

PMID- 23164304
TI  - Insights from studying prejudice in the context of American atheists.
AB  - Our research on non-religion supports the proposed shift toward more interactive
      models of prejudice. Being nonreligious is easily hideable and, increasingly, of
      low salience, leading to experiences not easily understood via traditional or
      contemporary frameworks for studying prejudice and prejudice reduction. This
      context affords new opportunity to observe reverse forms of interactive
      prejudice, which can interfere with prejudice reduction.

PMID- 23164306
TI  - Uncommon cause of large paravertebral calcification in a child.

PMID- 23164307
TI  - pH effects on cardiac function and systemic vascular resistance in preterm
      infants.
AB  - OBJECTIVE: To investigate the effect of pH on cardiac function and systemic
      vascular resistance (SVR) in preterm infants. STUDY DESIGN: In this prospective
      observational study, we evaluated hemodynamically stable, <= 30 weeks' gestation
      preterm infants during the first 2 postnatal weeks. Cardiac function was assessed
      by echocardiography at the time of arterial blood draw for clinically indicated
      blood gas analysis. Data were separately analyzed for the transitional (days 1-3)
      and post-transitional (days 4-14) periods. RESULTS: We evaluated 147 pairs of
      arterial blood gases and echocardiograms in 29 preterm neonates (gestational age
      = 26.2 +/- 1.5 weeks). Arterial pH ranged from 7.02-7.46. There was no linear
      relationship between pH and shortening fraction or stress-velocity index in
      transitional or post-transitional periods. We found a weak negative linear
      relationship between pH and left ventricular output and a positive linear
      relationship between pH and SVR only during the post-transitional period. These
      relationships were maintained after adjustment for the degree of base deficit.
      Arterial CO2 had effects similar to pH on myocardial function. CONCLUSIONS:
      Unlike adults, myocardial contractility remains relatively unaffected by acidosis
      even at pH values close to 7.00 in hemodynamically stable preterm neonates during
      the first 2 postnatal weeks. However, as in adults, worsening acidosis in preterm
      neonates after the immediate transitional period is associated with a decrease in
      SVR along with an increase in left ventricular output. Thus, although myocardial
      contractility remains unaffected in preterm neonates during the first 2 postnatal
      weeks, the vascular response to acidosis undergoes a relatively rapid postnatal
      maturational process.

PMID- 23164305
TI  - Comparison of quality of life after stereotactic body radiotherapy and surgery
      for early-stage prostate cancer.
AB  - BACKGROUND: As the long-term efficacy of stereotactic body radiation therapy
      (SBRT) becomes established and other prostate cancer treatment approaches are
      refined and improved, examination of quality of life (QOL) following prostate
      cancer treatment is critical in driving both patient and clinical treatment
      decisions. We present the first study to compare QOL after SBRT and radical
      prostatectomy, with QOL assessed at approximately the same times pre- and post
      treatment and using the same validated QOL instrument. METHODS: Patients with
      clinically localized prostate cancer were treated with either radical
      prostatectomy (n = 123 Spanish patients) or SBRT (n = 216 American patients). QOL
      was assessed using the Expanded Prostate Cancer Index Composite (EPIC) grouped
      into urinary, sexual, and bowel domains. For comparison purposes, SBRT EPIC data
      at baseline, 3 weeks, 5, 11, 24, and 36 months were compared to surgery data at
      baseline, 1, 6, 12, 24, and 36 months. Differences in patient characteristics
      between the two groups were assessed using Chi-squared tests for categorical
      variables and t-tests for continuous variables. Generalized estimating equation
      (GEE) models were constructed for each EPIC scale to account for correlation
      among repeated measures and used to assess the effect of treatment on QOL.
      RESULTS: The largest differences in QOL occurred in the first 1-6 months after
      treatment, with larger declines following surgery in urinary and sexual QOL as
      compared to SBRT, and a larger decline in bowel QOL following SBRT as compared to
      surgery. Long-term urinary and sexual QOL declines remained clinically
      significantly lower for surgery patients but not for SBRT patients. CONCLUSIONS:
      Overall, these results may have implications for patient and physician clinical
      decision making which are often influenced by QOL. These differences in sexual,
      urinary and bowel QOL should be closely considered in selecting the right
      treatment, especially in evaluating the value of non-invasive treatments, such as
      SBRT.

PMID- 23164308
TI  - A randomized clinical trial evaluating nasal continuous positive airway pressure
      for acute respiratory distress in a developing country.
AB  - OBJECTIVE: Invasive mechanical ventilation is often not an option for children
      with acute respiratory infections in developing countries. An alternative is
      continuous positive airway pressure (CPAP). The authors evaluated the
      effectiveness of CPAP in children presenting with acute respiratory distress in a
      developing country. STUDY DESIGN: A randomized, controlled trial was conducted in
      4 rural hospitals in Ghana. Children, 3 months to 5 years of age, presenting with
      tachypnea and intercostal or subcostal retractions or nasal flaring were randomly
      assigned to receive CPAP immediately or 1 hour after presentation. CPAP was
      applied by locally trained nurses. The primary outcome measure was change in
      respiratory rate at 1 hour. RESULTS: The study was stopped after the enrollment
      of 70 subjects because of a predetermined stop value of P < .001. Mean
      respiratory rate of children who received immediate CPAP fell by 16 breaths/min
      (95% CI 10-21) in the first hour compared with no change in children who had CPAP
      delayed by 1 hour (95% CI -2 to +5). Thirty-five of the patients had a positive
      malaria blood smear. There were 3 deaths as a result of severe malaria. No major
      complications of CPAP use were noted. CONCLUSIONS: CPAP decreases respiratory
      rate in children with respiratory distress compared with children not receiving
      CPAP. The technology was successfully used by local nurses. No complications were
      associated with its use. CPAP is a relatively low-cost, low-technology that is a
      safe method to decrease respiratory rate in children with nonspecific respiratory
      distress.

PMID- 23164309
TI  - Functional nonretentive fecal incontinence: do enemas help?
AB  - OBJECTIVE: To assess the current treatment of functional nonretentive fecal
      incontinence, which consists of education, toilet training, and positive
      motivation. STUDY DESIGN: Patients, age 6 years and older, referred for fecal
      incontinence (FI) and diagnosed with functional nonretentive fecal incontinence
      were eligible candidates. Seventy-one children (76% boys, median age 9.3 years)
      were randomized to receive conventional therapy (control group) or conventional
      therapy in addition to daily enemas during 2 weeks. Treatment success was defined
      as <2 episodes of FI/month without use of enemas. RESULTS: At intake, the median
      FI frequency was 6.1 per week, whereas the median defecation frequency was 7.0
      per week. At the end of the treatment period, the median number of FI episodes
      was significantly decreased in both groups: from 7.0 (IQR 4.0-11.5) to 1.0 (IQR
      0.5-2.0) in the intervention group and from 6.0 (IQR 4.0-10) to 2.0 (IQR 0.5-3.5)
      in the control group. No statistical difference was found between the groups at
      the end of the treatment period (P = .08) nor during additional follow-up
      (average success rate 17% for both groups, P = .99). CONCLUSION: Temporarily
      application of additional rectal enemas did not significantly improve treatment
      success compared with conventional therapy alone.

PMID- 23164310
TI  - Infant video viewing and salivary cortisol responses: a randomized experiment.
AB  - OBJECTIVE: To test the hypothesis that salivary cortisol levels respond
      differently when infants play with blocks compared with watching a digital video
      disk (DVD). STUDY DESIGN: We conducted a randomized experiment in which 8- to 14
      month-old infants either watched a DVD or played with blocks for 30 minutes.
      Serial salivary cortisol measurements were obtained and analyzed, and parental
      and infant responses and activities were recorded. Results were converted to
      standardized effect sizes (ESs) for clarity of presentation. RESULTS: A total of
      49 infants (49% female, mean age 10.6 months) participated in the study. In
      linear regression analyses, there was a trend toward higher cortisol levels in
      the block group at the 35-minute collection point (ES = 0.47, P = .08) and
      significantly higher levels at 45 minutes (ES = 0.56, P = .04); these salivary
      cortisol levels reflect serum levels approximately 10 and 20 minutes into the
      activity period, respectively. The results were substantially the same in
      sensitivity analyses excluding the outliers. CONCLUSION: Viewing by infants of a
      DVD leads to different neuroendocrine responses than block play in a laboratory
      setting. The implications of these differences are currently unknown, but may
      suggest different means of cognitive engagement between interactive play and DVD
      viewing.

PMID- 23164312
TI  - Screening in pediatrics-more questions than answers?

PMID- 23164311
TI  - Randomized trial of early developmental intervention on outcomes in children
      after birth asphyxia in developing countries.
AB  - OBJECTIVE: To determine if early developmental intervention (EDI) improves
      developmental abilities in resuscitated children. STUDY DESIGN: This was a
      parallel group, randomized controlled trial of infants unresponsive to
      stimulation who received bag and mask ventilation as part of their resuscitation
      at birth and infants who did not require any resuscitation born in rural
      communities in India, Pakistan, and Zambia. Intervention infants received a
      parent-implemented EDI delivered with home visits by parent trainers every other
      week for 3 years starting the first month after birth. Parents in both
      intervention and control groups received health and safety counseling during home
      visits on the same schedule. The main outcome measure was the Mental Development
      Index (MDI) of the Bayley Scales of Infant Development, 2nd edition, assessed at
      36 months by evaluators unaware of treatment group and resuscitation history.
      RESULTS: MDI was higher in the EDI (102.6 +/- 9.8) compared with the control
      resuscitated children (98.0 +/- 14.6, 1-sided P = .0202), but there was no
      difference between groups in the nonresuscitated children (100.1 +/- 10.7 vs 97.7
      +/- 10.4, P = .1392). The Psychomotor Development Index was higher in the EDI
      group for both the resuscitated (P = .0430) and nonresuscitated children (P =
      .0164). CONCLUSIONS: This trial of home-based, parent provided EDI in children
      resuscitated at birth provides evidence of treatment benefits on cognitive and
      psychomotor outcomes. MDI and Psychomotor Development Index scores of both
      nonresuscitated and resuscitated infants were within normal range, independent of
      early intervention.

PMID- 23164313
TI  - Large neutral amino acid supplementation increases melatonin synthesis in
      phenylketonuria: a new biomarker.
AB  - OBJECTIVE: To determine whether levels of melatonin in blood and urine can serve
      as a peripheral biomarker to reflect brain serotonin synthesis in individuals
      with phenylketonuria (PKU). STUDY DESIGN: We measured the levels of melatonin, a
      serotonin metabolite in the pinealocytes, in the blood and urine of individuals
      with PKU in a randomized double-blind placebo controlled crossover study
      consisting of three 3-week phases in 10 adults with PKU: phase 1 (washout), phase
      2 (supplementation of large neutral amino acid [LNAA] tablets or placebo), and
      phase 3 (alternate supplementation). An overnight protocol to measure blood
      melatonin and urine 6-sulfatoxymelatonin and dopamine in first void urine
      specimens was conducted after each phase for subjects with PKU and once in 10
      controls. RESULTS: Significantly lower concentrations of these neurotransmitter
      metabolites were observed in subjects with PKU after phase 1 compared with
      controls (serum melatonin P = .008, urine melatonin P = .0043, urine dopamine P <
      .0001), with significant increases after LNAA supplementation compared with the
      placebo phase (serum melatonin P = .0008, urine melatonin P = .0008, urine
      dopamine P = .0005). The mean tryptophan/LNAA and tyrosine/LNAA ratios were
      markedly lower in subjects with PKU compared with controls, and these ratios were
      significantly increased in the LNAA phase compared with the placebo phase (P =
      .016, P = .0003, respectively). Blood phenylalanine levels in subjects with PKU
      were not significantly different between placebo and LNAA phases (P = .74).
      CONCLUSION: Blood and urine melatonin levels may serve as biomarkers reflecting
      brain serotonin synthesis in subjects with PKU. Because this cannot be evaluated
      using blood phenylalanine levels, it may provide information on neurotransmitter
      metabolism for optimal dietary management.

PMID- 23164314
TI  - High rates of resolution of cholestasis in parenteral nutrition-associated liver
      disease with fish oil-based lipid emulsion monotherapy.
AB  - OBJECTIVE: To determine factors leading to resolution of cholestasis in patients
      with parenteral nutrition-associated liver disease treated with fish oil-based
      lipid emulsion (FOLE). STUDY DESIGN: Prospective observational study of 57
      infants <6 months of age with parenteral nutrition-associated liver disease who
      received parenteral FOLE as monotherapy. RESULTS: Median gestational age of
      subjects at birth was 28 weeks (range 22.7-39.5). Median conjugated bilirubin
      level at initiation of therapy with FOLE was 7.5 mg/dL (range 2.1-25). Resolution
      of hyperbilirubinemia (conjugated bilirubin <2.0 mg/dL) and survival to hospital
      discharge occurred in 47 (82.5%) infants. Median number of days to resolution of
      cholestasis was 35 (range 7-129). Ten infants (17.5%) died. Non-survivors showed
      a trend towards being more premature than survivors at birth (25.9 vs 29.1 weeks,
      P = .056). Infants with higher conjugated bilirubin at initiation of therapy
      (>10.0 compared with <5.0 mg/dL) had longer times to resolution (98 vs 56 days, P
      < .005). Time to resolution correlated inversely with gestational age at birth
      (r(2) = 0.14, P = .02) and directly with time to receive 100% calories enterally
      (r(2) = 0.12, P = .03). CONCLUSIONS: Younger gestational age infants demonstrated
      higher degree of cholestasis, longer time to resolution of cholestasis, and
      increased mortality. Higher levels of cholestasis were associated with longer
      time to resolution. FOLE monotherapy led to resolution of cholestasis in all
      surviving infants.

PMID- 23164315
TI  - Pediatric anti-N-methyl-D-aspartate receptor encephalitis-clinical analysis and
      novel findings in a series of 20 patients.
AB  - OBJECTIVE: To report the clinical features of 20 pediatric patients with anti-N
      methyl-D-aspartate receptor (NMDAR) encephalitis. STUDY DESIGN: Review of
      clinical data, long-term follow-up, and immunologic studies performed in a single
      center in Spain in the last 4 years. RESULTS: The median age of the patients was
      13 years (range, 8 months-18 years), 70% were female. In 12 patients (60%), the
      initial symptoms were neurologic, usually dyskinesias or seizures, and in the
      other 40% psychiatric. One month into the disease, all patients had involuntary
      movements and alterations of behavior and speech. All patients received steroids,
      intravenous immunoglobulin or plasma exchange, and 7 rituximab or
      cyclophosphamide. With a median follow up of 17.5 months, 85% had substantial
      recovery, 10% moderate or severe deficits, and 1 died. Three patients had
      previous episodes compatible with anti-NMDAR encephalitis, 2 of them with
      additional relapses after the diagnosis of the disorder. Ovarian teratoma was
      identified in 2 patients, 1 at onset of encephalitis and the other 1 year later.
      Two novel observations (1 patient each) include, the identification of an
      electroencephalographic pattern ("extreme delta brush") considered characteristic
      of this disorder, and the development of anti-NMDAR encephalitis as post herpes
      simplex encephalitis choreoathetosis. CONCLUSIONS: The initial symptoms of
      pediatric anti-NMDAR encephalitis vary from those of the adults (more neurologic
      and less psychiatric in children), the development of a mono-symptomatic illness
      is extremely rare (except in relapses), and most patients respond to treatment.
      Our study suggests a link between post herpes simplex encephalitis
      choreoathetosis and anti-NMDAR encephalitis.

PMID- 23164317
TI  - Femoral fracture as a rare presentation of prepubertal graves disease.

PMID- 23164316
TI  - Health outcomes among youths and adults with spina bifida.
AB  - OBJECTIVE: To describe the health and health-related quality of life (HR-QoL)
      outcomes of youths and young adults with spina bifida. STUDY DESIGN: One global
      rating of self-rated health and 2 generic measures of HR-QoL were administered to
      a group of youths and young adults with spina bifida. HR-QoL was measured using
      the Health Utilities Index Mark 3 (HUI3) and the Assessment of Quality of Life
      version 1 (AQoL). RESULTS: Data was obtained from 40 youth (mean age 16.0 years)
      and 13 young adults (mean age 26.6 years). Most youth rated their overall health
      as either excellent or very good (65%) compared with fewer adults (23%) (P =
      .007). The mean HR-QoL scores for youths versus adults were 0.57 versus 0.36 (P =
      .03) for the HUI(3) and 0.37 versus 0.25 for the AQoL (P = .09). HUI(3) and AQoL
      scores were correlated with level of anatomic lesion (rho = 0.64 and rho = 0.42,
      respectively). CONCLUSIONS: The HR-QoL of youths and young adults with spina
      bifida was low on measures that are aggregated using societal values (the HUI3
      and AQoL). This is in contrast to their single global self-ratings of health,
      which were more favorable. These findings underscore the distinction between
      ratings of HR-QoL based on societal values versus the personal lived experiences
      of adults with childhood-onset disability.

PMID- 23164318
TI  - Active case detection in national visceral leishmaniasis elimination programs in
      Bangladesh, India, and Nepal: feasibility, performance and costs.
AB  - BACKGROUND: Active case detection (ACD) significantly contributes to early
      detection and treatment of visceral leishmaniasis (VL) and post kala-azar dermal
      leishmaniasis (PKDL) cases and is cost effective. This paper evaluates the
      performance and feasibility of adapting ACD strategies into national programs for
      VL elimination in Bangladesh, India and Nepal. METHODS: The camp search and index
      case search strategies were piloted in 2010-11 by national programs in high and
      moderate endemic districts / sub-districts respectively. Researchers
      independently assessed the performance and feasibility of these strategies
      through direct observation of activities and review of records. Program costs
      were estimated using an ingredients costing method. RESULTS: Altogether 48 camps
      (Bangladesh-27, India-19, Nepal-2) and 81 index case searches (India-36, Nepal
      45) were conducted by the health services across 50 health center areas
      (Bangladesh-4 Upazillas, India-9 PHCs, Nepal-37 VDCs). The mean number of new
      case detected per camp was 1.3 and it varied from 0.32 in India to 2.0 in
      Bangladesh. The cost (excluding training costs) of detecting one new VL case per
      camp varied from USD 22 in Bangladesh, USD 199 in Nepal to USD 320 in India. The
      camp search strategy detected a substantive number of new PKDL cases. The major
      challenges faced by the programs were inadequate preparation, time and resources
      spent on promoting camp awareness through IEC activities in the community.
      Incorrectly diagnosed splenic enlargement at camps probably due to poor clinical
      examination skills resulted in a high proportion of patients being subjected to
      rK39 testing. CONCLUSION: National programs can adapt ACD strategies for
      detection of new VL/PKDL cases. However adequate time and resources are required
      for training, planning and strengthening referral services to overcome challenges
      faced by the programs in conducting ACD.

PMID- 23164319
TI  - A feedback framework for protein inference with peptides identified from tandem
      mass spectra.
AB  - BACKGROUND: Protein inference is an important computational step in proteomics.
      There exists a natural nest relationship between protein inference and peptide
      identification, but these two steps are usually performed separately in existing
      methods. We believe that both peptide identification and protein inference can be
      improved by exploring such nest relationship. RESULTS: In this study, a feedback
      framework is proposed to process peptide identification reports from search
      engines, and an iterative method is implemented to exemplify the processing of
      Sequest peptide identification reports according to the framework. The iterative
      method is verified on two datasets with known validity of proteins and peptides,
      and compared with ProteinProphet and PeptideProphet. The results have shown that
      not only can the iterative method infer more true positive and less false
      positive proteins than ProteinProphet, but also identify more true positive and
      less false positive peptides than PeptideProphet. CONCLUSIONS: The proposed
      iterative method implemented according to the feedback framework can unify and
      improve the results of peptide identification and protein inference.

PMID- 23164320
TI  - Understanding the psychological processes involved in the demobilizing effects of
      positive cross-group contact.
AB  - A theoretical framework is required that explains why and how cross-group contact
      reduces collective action and how the demobilizing effects can be counteracted.
      We propose that at least two mechanisms are involved: an affective process
      whereby the positive affect created offsets negative emotions and action
      tendencies, and a more strategic process whereby individual advancement comes to
      seem like a possibility.

PMID- 23164321
TI  - A novel biotechnology product for the degradation of biofilm-associated
      polysaccharides produced by Streptococcus mutans.
AB  - In this study we evaluated the activity of ABR preparation, a first-in-class
      agent obtained through fermentation process by genetically unmodified Bacillus
      spp., in breaking down polysaccharide produced by Streptococcus mutans, primary
      coloniser of tooth surface and abundant in dental biofilms. Our results showed
      that ABR preparation is able in degrading sugars formed by S. mutans, both in
      broth culture and onto teeth surface. Its activity is not influenced by the
      presence of saliva, commercial mouthwashes or oral disinfectants. ABR preparation
      has the potential to remove preformed plaque and counteract its development, thus
      offering conservative control of gingival and periodontal disease.

PMID- 23164322
TI  - Microbiologic evaluation of crevicular fluid in patients treated with platform
      switching and traditional implants.
AB  - BACKGROUND: The purpose of this study was to compare the microbiota around
      natural teeth and dental implants with different restorative platforms. Attention
      was focused on whether the microbiological environment could change according to
      the implant platform used i.e. traditional or Platform Switching implants. As the
      latter show less signs of bone resorption, a correlation with the presence of
      certain periodontal bacteria was suggested. METHODS: Seven partially edentulous
      patients with dental implants, either traditional or Platform Switching, were
      included in this study. All the implants were in function at least for 1 year.
      Gingival crevicular fluid samples were obtained before any periodontal probing
      from natural teeth and different implant platforms and assayed using DNA
      extraction and PCR sequences in order to determine quality and quantity of
      microbiota. Statistical analysis included chi square test were used to establish
      differences in the microbiological distribution between the two implant
      platforms. RESULTS: There were not statistical differences neither regarding the
      distribution of microbiota around natural teeth and implants nor between the two
      implant platforms. The presence of B.forsythus was revealed in the majority of
      the samples (from 90 to 100 percent) while A.actinomycetemcomitans was rarely
      found (from 0 o 25 percent). As for the other periodontal microbiota, their
      presence or absence showed a variation according to different sites or patients,
      without a predictable pattern. CONCLUSIONS: It was not possible to find a link
      between the colonization of certain types of bacteria and the reduction of bone
      loss which occurs around Platform Switching implants. Therefore the preservation
      of bone crest is only due to biomechanical aspects, which are related to the
      reposition of the implant-abutment interface away from the outer edge of the
      implant platform and from the bone.

PMID- 23164323
TI  - Histological and histomorphometric evaluation of implant with nanometer scale and
      oxidized surface. in vitro and in vivo study.
AB  - BACKGROUND: The biological fixation of an implant to bone is influenced by
      numerous factors, including surface chemistry and surface topography. Various
      methods have been developed to create rough implant surfaces in order to improve
      the clinical performance of implants and to guarantee a stable mechanical bone
      implant interface. Anodic oxidation is a dental implant surface modification
      technique that results in oxide layer growth up to a thickness of 1?10 micron.
      The purpose of this study was to evaluate the performance of the surface through
      the osteoblasts cells growth and the influence of oxidixed surface on BIC
      percent, in the human posterior maxilla after 2 months of unloaded healing.
      MATERIAL AND METHODS: In vitro commercially available primary human osteoblasts
      (NHOst) from both femur and tibia of different donor systems (Lonza Walkersville
      Inc, Walkersville, MD, USA) were grown in Osteoblast Growth Media (OBM) (Lonza).
      Osteogenic differentiation was induced for a period of 4 weeks by the OGM medium
      (OBM basal medium supplemented with 200nM of hydrocortisone-21-hemisuccinate and
      7.5 mM of glycerophosphate). The viability of NHOst cells seeded test A and B was
      measured by the quantitative colorimetric MTT (3-[4,5-dimethyl-2-thiazolyl]-2,5
      diphenyl-2Htetrazoliumbromide test) (Promega, Milan, Italy). One custom-made 2 x
      10-mm site evaluation implant (SEI) with nanometer scale and oxidized surface
      (test) ( Evo Plan 1 Health s.r.l. - Amaro, UD, Italy), and one SEI with
      hydroxyapatite sandblasted surface (control) (Osseogrip Plan 1 Health s.r.l. ?
      Amaro, UD, Italy), were placed in the posterior maxilla of 15 patients. Patients
      received one of each type of SEI placed on controlateral side. RESULTS: The
      proliferation rate studied by the MTT assay showed that during the incubation
      time, starting at 24 h, an increased proliferation rate was evident in Test B
      respect to Test A. After 2 months of unloaded healing BIC percent was
      significantly higher in oxidized implants. BIC percent mean values for the
      Osseogrip surface was 36,133 +/-4,888 ER and 53,533 +/- 5,180 ER for the Evo
      surface(P = 0,028). CONCLUSION: These results seem to confirm that implant
      surface topography entails mechanical restrictions to the spread and locomotion
      of the cells involved in bone healing.

PMID- 23164324
TI  - Effects of bisphosphonates in orthodontic therapy:systematic review.
AB  - BACKGROUND: Currently, the use of oral and systemic bisphosphonates, in the form
      of anti-osteoporosis medications or as a part of a chemotherapeutic regimen for
      several malignant diseases, is increasing dramatically in a large group of
      orthodontic patients. Animal studies have reported adverse dental effects from
      bisphosphonates, including decreased tooth movement, impaired bone healing, and
      osteonecrosis in the mandible and the maxilla. OBJECTIVE: The objective of this
      paper was to analyze the effects of bisphosphonates on orthodontic therapy in
      humans. STRATEGY: The literature was systematically reviewed using PubMed, LILACS
      and OvidMedline up to December 31, 2011. Handsearching included several dental
      journals. STUDY SELECTION: All RCT?s, controlled trials and case reports-series
      about the effects of bisphosphonates on orthodontic therapy were analyzed and
      selected independently by two different researchers based on previously
      established inclusion and exclusion criteria. The main search terms were:
      bisphosphonates, orthodontic treatment and tooth movement. RESULTS: The search
      strategy yielded 136 titles/abstracts: 134 from PubMed and 2 from LILIACS; no
      articles from OvidMedline, Chocrane Library and manual search. Eighty three
      records were screened, after removal of duplicates. After applying the
      inclusion/exclusion criteria, 135 papers were removed: 43 studies on animals, 4
      French and Portuguese articles, 17 reviews and letters, 18 unrelated to
      orthodontic therapy or to the topic of this review. CONCLUSIONS: Further studies
      are required to assess possible adverse effects of bisphosphonate on orthodontic
      treatment in humans.

PMID- 23164325
TI  - Endodontic-orthodontic relationships: expression of no synthase in human dental
      pulp during orthodontic tooth movement.
AB  - Inflamed human pulp tissue presents an increase in the level of nitric oxide
      synthase (NOS). The aim of this study is to verify the presence of NOS in human
      pulp of teeth that are subject to orthodontic force. 20 healthy subjects, wearers
      of fixed braces on the upper arch, were selected. An open coil-spring in NiTi was
      applied on the upper premolar test tooth (TT); the controlateral control tooth
      (CCT) was subjected to orthodontic treatment but not to the further force of the
      open coil-spring; the antagonist control tooth (ACT) did not undergo any
      orthodontic treatment. Pulps were taken from test, contralateral control and
      antagonist control teeth immediately after the extractions which were done at 15
      and 30 days from the start of application of the orthodontic force. The pulp
      tissue was analyzed through immunohistochemical and molecular biology
      examinations. The results showed tooth pulps subject to orthodontic treatment
      were very inflamed in the first 15 days with high levels of iNOS and low levels
      of eNOS; after 30 days a decrease of the inflammation and an increase of the pulp
      vascularization were observed together with a reduction of iNOS and an increase
      of eNOS respectively.

PMID- 23164326
TI  - Microarray evaluation of gene expression profiles in inflamed and healthy human
      dental pulp: the role of IL1beta and CD40 in pulp inflammation.
AB  - Dental pulp undergoes a number of changes passing from healthy status to
      inflammation due to deep decay. These changes are regulated by several genes
      resulting differently expressed in inflamed and healthy dental pulp, and the
      knowledge of the processes underlying this differential expression is of great
      relevance in the identification of the pathogenesis of the disease. In this
      study, the gene expression profile of inflamed and healthy dental pulps were
      compared by microarray analysis, and data obtained were analyzed by Ingenuity
      Pathway Analysis (IPA) software. This analysis allows to focus on a variety of
      genes, typically expressed in inflamed tissues. The comparison analysis showed an
      increased expression of several genes in inflamed pulp, among which IL1&#946; and
      CD40 resulted of particular interest. These results indicate that gene expression
      profile of human dental pulp in different physiological and pathological
      conditions may become an useful tool for improving our knowledge about processes
      regulating pulp inflammation.

PMID- 23164327
TI  - Thermal analysis of laser-softened gutta-percha.
AB  - The aim of this work is to examine the behaviour of laser treated gutta-percha
      (a?b) after heating, to test the validity of a new obturation technique. Samples
      of laser- and no laser- treated gutta-percha have been examined by the
      thermal/thermogravimetric analysis and compared. All samples have been submitted
      to four runs of heating from the temperature of 25?130 C, followed by spontaneous
      cooling. It was found that some samples have shown the typical behaviour of the
      alpha-gutta-percha; others have shown characteristics similar to the conventional
      beta-gutta-percha. The laser treated gutta-percha has shown a significant mass
      loss after the first run of heating, while the mass tends to stabilize after the
      third run. It has been demonstrated that the 980 nm diode laser used with cited
      parameters does not alters thermal behaviour of gutta-percha cones.

PMID- 23164328
TI  - In vitro evaluation of mesenchymal stem cell isolation possibility from different
      intra-oral tissues.
AB  - Mesenchymal stem cells (MSCs) are of great interest for the regeneration of
      tissues and organs. Bone marrow is the first sources of MSCs, but in the recent
      years there has been interest in other tissues for the isolation of these
      pluripotent cells. In this study, we investigated the features of MSCs isolated
      from different oral regions in order to evaluate their potential application in
      the regeneration of damaged maxillofacial tissues. Sampling from human
      periodontal ligament, dental pulp, maxillary periosteum as well as bone marrow
      were collected in order to obtain different stem cell populations. Cells were
      morphologically and immunophenotipically characterized. Their proliferation
      potential and their ability to differentiate in osteoblasts were also assessed.
      All tested cell population showed a similar fibroblast-like morphology and
      superimposable immunophenotype. Slight differences were observed in proliferation
      and differentiation potential. Cells isolated from human periodontal ligament,
      dental pulp, maxillary periosteum had the characteristics of stem cells.
      Considering their peculiar feature they may alternatively represent interesting
      cell sources in stem cell-based bone/periodontal tissue regeneration approaches.

PMID- 23164329
TI  - Antibiotic-modified hydrogel coatings on titanium dental implants.
AB  - Implant-associated infections represent an occasional but serious problem in
      dental and/or orthopaedic surgery. A possible solution to prevent the initial
      bacterial adhesion may be the coating of the implant surface with a thin layer of
      antibiotic-loaded biocompatible polymer. Hydrogels are one of the promising and
      versatile materials as antibiotic controlled release systems. In this work,
      antibiotic-modified poly(ethylene-glycol diacrylate) hydrogel coatings on
      titanium substrates were prepared by electrochemical polymerization and tested
      against methicillin resistant Staphylococcus aureus (ATCC 33591). Two different
      methods to load vancomycin and ceftriaxone were used. We show that the proposed
      titanium coatings displayed an interesting antibacterial activity, however,
      further studies on their effective cytotoxicity will furnish evidence of their
      real clinical efficacy.

PMID- 23164330
TI  - Two-step impression/ injection, an alternative putty/ wash impression technique:
      case report.
AB  - We here describe a new technique for making a definitive impression that we refer
      to as the two-step impression/injection technique. This technique initially
      follows the classical one-step putty/ light-body impression technique with the
      polymerization of the putty and the light-body compound. This is then followed by
      the second step: injection of extra-light-body compound into the preparation
      through a hole in the metal stock tray. The aim of this additional step is to
      control the wash bulk and minimize the changes that can produce unfavorable
      impression results. This new two-step impression/injection technique allows
      displacement of soft tissues, such as the tongue, during the first seating of the
      putty and wash materials, while in the second step, the extra-light-body compound
      records all of the finer details without being compressed.

PMID- 23164331
TI  - Late development of a supernumerary premolar in a 17-year-old female: timing of
      mineralization and medicolegal considerations.
AB  - This report presents a case of a patient who developed a mandibular premolar
      supernumerary tooth after 14 years of age. Panoramic radiographs show the
      complete absence of the tooth (or tooth lacuna) at 14 years of age, and the crown
      as 50 percent developed at 17 years of age. The panoramic radiograph and computed
      tomography show dislocation of the roots of the adjacent teeth and a morphology
      similar to a premolar. Although the patient concluded the orthodontic treatment
      just before the premolar detection on any panoramic radiograph, the parents of
      the patient complained about the poor information received from the orthodontist.

PMID- 23164332
TI  - Micromorphometrical and histological analyses using two different oscillating
      osteotomy techniques compared with conventional rotary osteotomy.
AB  - The recently introduced ultrasonic osteotome procedure is an alternative to
      conventional rotatory burs. The aim of this study was to establish the
      differences between two ultrasonic osteotomes and conventional rotatory burs, in
      order to perform micromorphological and histological analyses of osteotomized
      bone surfaces. Bony samples were taken from adult bovine ribs including both the
      cortical and marrow bone. Soft tissues have been removed and the bone pieces were
      divided into four groups, to test four devices: a conventional osteotomy round
      bur, a Lindeman bur and piezoelectric osteotomes ES007 and the T-Black. Each
      device performed cuts that were examined via scanning electron microscope (SEM)
      and light microscopy (LM) to check respectively cut precision and bone
      architecture all along the defect borders. SEM analysis of specimens showed that
      burs created defects of greater width and with irregular edges while those
      produced by ultrasonic osteotomes were narrow and had mostly smooth cutting
      surfaces. The edges of incisions made by drills were full of bone fragments while
      less bone chips were observed on piezoincision?s ones. Dimensions of fragments
      were wider if cuts were made by burs too. LM analysis of samples showed focally,
      delicate bony trabecules crushed and pressed into the bone marrow in cutting made
      by burs. Samples cut by ultrasonic devices showed small or no smear layer and
      only partial or no crushed trabecules. Osteocytes seemed to be intact all along
      the cutting surface in all samples observed. In the present study, according to
      literature, ultrasonic surgery validity is confirmed. As a matter of fact, the
      greater the number of bone chips products, the greater the magnitude of the
      inflammatory process induced, as well as the possibility of a greater bone loss
      and delay in wound healing near the osteotomized area.

PMID- 23164333
TI  - Subjective pain response to two anesthetic systems in dental surgery: traditional
      syringe vs. a computer controlled delivery system.
AB  - The present study was conducted to evaluate human pain perception at different
      phases of dental surgery using a computer controlled device, the Single Tooth
      Anesthesia System (STA System), versus the traditional syringe technique. One
      hundred healthy patients participated in this single-blind split-mouth design
      study. Individuals provided pain ratings at needle insertion, delivery of
      anesthetic solution and tooth extraction via a numeric visual rating scale or
      NVRS. The anterior middle superior alveolar, or AMSA, injection was compared with
      traditional syringe injections in maxillary quadrants. NVRS scores for AMSA were
      significantly lower for the STA System when compared to traditional syringe
      technique at needle insertion, delivery of anesthetic solution (p less than
      0.0001) and also during tooth extractions (p=0.0002). A higher percentage of
      patients (23 percent) required a second injection after the traditional syringe
      technique. Subjects reported having less clinical pain with AMSA injection at
      every step of the dental surgery. The STA System combines an anesthetic pathway
      and controlled flow rate resulting in virtually imperceptible needle insertion
      and injection, and a rapid onset of profound anesthesia. NVRS scoring system
      facilitated patient comprehension in assessing pain value and intensity
      experienced. The two anesthetic delivery techniques were therapeutically
      equivalent for maxillary injections but AMSA/computer controlled protocol
      significantly minimizes subjective pain perception at needle insertion,
      anesthetic delivery and during tooth extraction.

PMID- 23164334
TI  - Hyperspectral cathodoluminescence imaging and analysis extending from ultraviolet
      to near infrared.
AB  - The measurement of near-infrared (NIR) cathodoluminescence (CL) with sufficient
      sensitivity to allow full spectral mapping has been investigated through the
      application of optimized grating spectrometers that allow the ultraviolet (UV),
      visible, and NIR CL spectra to be measured simultaneously. Two optical
      spectrometers have been integrated into an electron microprobe, allowing
      simultaneous collection of hyperspectral CL (UV-NIR), characteristic X-rays, and
      electron signals. Combined hyperspectral CL spectra collected from two natural
      apatite (Ca5[PO4]3[OH,F]) samples from Wilberforce (Ontario, Canada) and Durango
      (Mexico) were qualitatively analyzed to identify the emission centers and then
      deconvoluted pixel-by-pixel using least-squares fitting to produce a series of
      ion-resolved CL intensity maps. Preliminary investigation of apatite has shown
      strong NIR emissions associated primarily with the rare-earth element Nd. Details
      of growth and alteration were revealed in the NIR that were not discernable with
      electron-induced X-ray mapping. Intense emission centers from Nd3+ and Sm3+ were
      observed in the spectra from both apatites, along with minor emissions from other
      3+ rare-earth elements. Quantitative electron probe microanalysis was performed
      on points within the mapped area of the Durango apatite to produce a calibration
      line relating cathodoluminescent intensity of the fitted peak centered at 1,073
      nm (1.156 eV) to the Nd concentration.

PMID- 23164335
TI  - Fracture resistance of simulated immature maxillary anterior teeth restored with
      fiber posts and composite to varying depths.
AB  - BACKGROUND: Traumatized immature teeth present a unique challenge during
      treatment, both endodontically as well as restoratively. Hence, the purpose of
      this study is to evaluate the type and depth of restoration that would be
      effective in simulated immature maxillary anterior teeth in terms of fracture
      resistance and mode of failure. MATERIALS AND METHODS: Seventy-five extracted
      human maxillary anterior teeth were used in this study that was standardized to a
      length of 13 mm. Instrumentation of the canals was performed after which a Peezo
      no. 6 was taken 1 mm past the apex to simulate an incompletely formed root. MTA
      apexification was simulated after which all the teeth were mounted and a 3-mm
      diameter engineering twist drill extended the preparation 3 and 7 mm below the
      facial cemento-enamel junction (CEJ) to simulate Cvek's stage 3. These teeth were
      divided into seven different groups: Group 1: Negative control: intact teeth;
      Group 2: Positive control: 3 mm, no restoration; Group 3: Positive control: 7 mm,
      no restoration; Group 4: 3-mm composite; Group 5: 3-mm quartz fiber post; Group
      6: 7-mm composite; Group 7: 7-mm quartz fiber post. Fracture resistance was
      performed at 130 degrees  to the long axis of the tooth with a chisel-shaped tip
      at the cingulum with a cross-head speed of 5 mm min(-1) , and the maximum load at
      which the fracture occurred was recorded. RESULTS: Group 1 that was the negative
      control showed the highest fracture resistance. Among the experimental groups, 4
      and 5 showed the highest fracture resistance, which were significantly different
      from groups 6 and 7, respectively. CONCLUSIONS: Within the limitations of this in
      vitro study, it can be concluded that using either dual-cure composite or a
      quartz fiber post with composite resin to a depth of 3 mm would significantly
      strengthen the roots in immature teeth.

PMID- 23164336
TI  - Outbreaks and diagnosis of foot-and-mouth disease serotype O in the Republic of
      Korea, April-June 2010.
AB  - Thirteen outbreaks of foot-and-mouth disease (FMD) were reported in pigs and
      cattle in Korea between 8 April and 4 June 2010. The FMD virus (FMDV) isolates
      were of serotype O, indicating that they were related to the virus strains of the
      Southeast Asia topotype that are circulating in East Asian countries. Animals
      carrying the viruses were identified by reverse transcriptase-polymerase chain
      reaction (RT-PCR) during a 29-day period between 8 April and 6 May, 2010. Prior
      to this outbreak, these FMDVs had not been detected in Korea and may therefore
      have been introduced from neighbouring countries into Ganghwa Island and
      subsequently spread inland to other areas, including Gimpo, Chungju and
      Cheongyang. Tests conducted to lift restrictions on animal movements lead to
      detection of two additional FMD-positive farms. Through appropriate responses,
      including swift diagnoses and culling policies, Korea was able to quickly regain
      its recognition as being free of FMD, without vaccination, by the World
      Organization for Animal Health (OIE) on 27 September 2010.

PMID- 23164337
TI  - TissuePatchTM as a novel synthetic sealant for repair of superficial lung defect:
      in vitro tests results.
AB  - BACKGROUND: Controversies surrounding the efficacy of surgical sealants against
      alveolar air leaks (AAL) in lung surgery abound in the literature. We sought to
      test the sealing efficacy of a novel synthetic sealant, TissuePatchTM in an in
      vitro lung model. METHODS: The lower lobe of freshly excised swine lung (n = 10)
      was intubated and ventilated. A superficial parenchymal defect (40 * 25 mm) was
      created, followed by AAL assessment. After sealant application, AAL was assessed
      again until burst failure occurred. The length of defect was recorded to evaluate
      the elasticity of the sealant. RESULTS: Superficial parenchymal defects resulted
      in AAL increasing disproportionally with ascending maximal inspiratory pressure
      (Pmax). Multiple linear regression analysis revealed strong correlation between
      AAL and Pmax, compliance, resistance. After sealant application, AAL was sealed
      in all ten tests at an inspired tidal volume (TVi) of 400 ml, in nine tests at
      TVi = 500 ml, in seven at TVi = 600 ml and in five at TVi = 700 ml. The mean
      burst pressure was 42 +/- 9 mBar. Adhesive and cohesive sealant failures were
      found in six and three tests respectively. The length of defect before sealant
      failure was 8.9 +/- 4.9% larger than that at TVi = 400 ml, demonstrating an
      adequate elasticity of this sealant film. CONCLUSIONS: TissuePatchTM may be a
      reliable sealant for alternative or adjunctive treatment for repair of
      superficial parenchymal defects in lung surgery. The clinical benefits of this
      sealant should be confirmed by prospective, randomised controlled clinical
      trials. ABSTRAKT: HINTERGRUND: Die Wirksamkeit von chirurgischen Klebstoffen zur
      Pravention von alveolo-pleuralem Luftleck (APL) ist trotz zunehmenden klinischen
      Anwendungen in Lungenchirurgie immer noch kontrovers diskutiert. Wir evaluierten
      die Abdichtungswirksamkeit von einem neuartigen synthetischen Kleber,
      TissuePatchTM mittels eines in vitro Lungenmodels. METHODE: Der Unterlappen von
      frisch entnommenen Schweinlungen (n = 10) wurde intubiert und beatmet. Eine
      pleurale Lasion (40 * 25 mm) wurde erstellt und APL mit steigendem
      inspiratorischem Tidalvolumen (TVi) untersucht. Nach Applikation von
      TissuePatchTM wurde APL auf die gleiche Weise gemessen bis zur Auftritt von
      Kleberbruch. Zur Untersuchung der Elastizitat des Klebers wurde die Lange der
      pleuralen Lasion gemessen. ERGEBNIS: Pleurale Lasion fuhrte bei aufsteigendem
      maximalem inspiratorischem Druck (Pmax) zu uberproportionalem Anstieg von APL.
      Multiple lineare Regressionsanalyse ergab eine starke Korrelation zwischen APL
      und Pmax, Lungencompliance sowie Widerstand. Nach der Applikation von Klebstoff
      wurde APL bei TVi = 400 ml in allen zehn Testen versiegelt, bei TVi = 500 ml in
      neun Testen, bei TVi = 600 ml in sieben und bei TVi = 700 ml in funf Testen. Der
      mittlere Pmax, der zu Kleberbruch fuhrte, betrug 42 +/- 9 mBar. Bei den Versuchen
      wurden adhasiver und kohasiver Kleberbruch in jeweils sechs und drei Testen
      gefunden. Die Lange der pleuralen Lasion vor dem Kleberbruch war 8,9 +/- 4,9%
      grobetaer als die bei TVi = 400 ml. SCHLUSSFOLGERUNG: Unsere Versuche zeigten
      eine zuverlassige Versiegelung von TissuePatchTM unter mechanischer Ventilation.
      Die klinische Nutzlichkeit vom Kleber als unterstutzende Mabetanahme zur
      Pravention von alveolo-pleuralem Luftleck in Lungenchirurgie sollte durch
      prospektive, randomisierte kontrollierte klinische Studien bestatigt werden.

PMID- 23164338
TI  - The in vitro and in vivo developmental capacity of selected porcine monospermic
      zygotes.
AB  - In this study, we evaluated the in vitro and in vivo developmental capacity of
      selected monospermic zygotes produced in vitro. Cumulus-oocyte complexes were
      matured in vitro and inseminated with frozen-thawed spermatozoa. Thirteen hours
      after insemination, presumptive zygotes were centrifuged at 15,000 *g for 20
      minutes to polarize the lipids in the cytoplasm and permit the visualization of
      pronuclei. Then, the oocytes were individually classified as bipronuclear (2PN)
      or polypronuclear (three or more pronuclei, PPN). To examine embryo development,
      102 selected zygotes were cultured for 7 days. There were no differences in
      cleavage rate (93.0% and 88.9% for 2PN and PPN zygotes, respectively). However,
      the blastocyst formation rate was higher (P < 0.003) in 2PN (80.7%) zygotes than
      in PPN (53.3%) zygotes. The control (noncentrifuged, nonselected zygotes) group
      showed lower (P < 0.003) cleavage rate and blastocyst formation than the 2PN and
      PPN zygotes. In a second experiment, 2PN zygotes and control zygotes were
      transferred (30 zygotes per transfer) by laparoscopy into the oviducts of
      recipient gilts (10 recipients per group) on the first day of standing estrus.
      The farrowing rates were 70% and 40% for transfers made with 2PN and control
      zygotes, respectively. The average number of piglets born per recipient farrowed
      did not differ between groups (4.9 +/- 0.6 and 4.5 +/- 1.2, respectively), but
      the efficiency (number of live piglets per total transferred embryos) was higher
      (P < 0.01) for 2PN zygotes than for the control group (9.3% and 4.0%,
      respectively). These results demonstrate the effectiveness of centrifugation for
      the selection of monospermic zygotes as a procedure to improve in vitro embryo
      production in pigs. In addition, the results indicate that the laparoscopic
      technique described here is a simple and effective procedure for transferring
      embryos into one oviduct.

PMID- 23164339
TI  - Prejudice is about politics: a collective action perspective.
AB  - In line with Dixon et al.'s argument, I contend that prejudice should be
      understood in broadly political rather than in narrowly psychological terms.
      First, what counts as prejudice is a political judgement. Second, studies of
      collective action demonstrate that it is in "political" struggles, where
      subordinate groups together oppose dominant groups, that prejudice can be
      overcome.

PMID- 23164340
TI  - Cholesterol and phospholipids in frontal cortex and synaptosomes of suicide
      completers: relationship with endosomal lipid trafficking genes.
AB  - Cholesterol (CHL) and phospholipid (PL) levels in synaptosomal membranes in
      particular can have an impact on cell signalling. Alterations in peripheral CHL
      measures have been consistently reported in suicidal behaviour. As CHL and PL
      turnover in the brain are important in synapse maintenance and function, the
      objective of this study was to determine if differences exist in synaptosomal
      cholesterol and phospholipid levels between suicide completers and controls.
      Expression measures of genes involved in lipid trafficking suggest an association
      between Lysosomal acid lipase A, cholesteryl ester hydrolase (LIPA) and brain PL
      levels, with LIPA being significantly increased in violent suicides and
      associated with alterations in brain PL. The results of this study suggest an
      altered PL content mediated by LIPA expression in violent suicides in the
      prefrontal cortex, which would have important consequences for inhibitory
      neurotransmission.

PMID- 23164342
TI  - Inferior turbinate mucosal graft combined with radiofrequency for the treatment
      of nasal hereditary haemorrhagic telangiectasia: our experience in sixteen
      patients.

PMID- 23164341
TI  - Study of treatment using percutaneous acetabuloplasty and interstitial
      implantation of (125)I seeds for patients with metastatic periacetabular tumors.
AB  - BACKGROUND: The periacetabular area is one of the primary sites of metastatic
      tumors, which often present as osteolytic bone destruction. Bone destruction in
      the acetabulum caused by metastatic tumors will cause hip pain and joint
      dysfunction. It results in decreased quality of life for patients. The aim of our
      study was to explore the clinical effect of metastatic periacetabular tumors
      treated with percutaneous cementoplasty and interstitial implantation of (125)I
      seeds. METHODS: A retrospective analysis was performed on 24 patients with
      metastatic periacetabular tumors who underwent combined therapy of percutaneous
      acetabuloplasty and interstitial implantation of (125)I seeds between February
      2003 and June 2011. There were 13 males and 11 females aged 19-80 years with a
      mean age of 57.3. The primary tumor site was the lung in eight cases, the breast
      in six, the prostate cancer in eight, and the liver in two. The amount of
      implanted (125)I seeds was 12-20 seeds/person, with a mean of 16.5 seeds/person,
      and the matching peripheral dosage (MPD) was 80~100Gy. Routine postoperative
      chemotherapy and other combined treatments were applied to patients after the
      surgical operation. Changes in the Karnofsky Score(KPS), Harris Hip
      Score(Harris), and Visual Analog Scale(VAS) were observed during the follow-up
      period. RESULTS: The 24 patients' operations were all successful. No major
      complications occurred. Complete pain relief was achieved in 58% (14 of 24) of
      patients, and pain reduction was achieved in the 42% remaining (10) patients. The
      mean duration of pain relief was 8.3 months. Pain recurred in one patient 3
      months after surgery. Six patients had died and 18 patients were alive at the
      time of the 1-year follow-up. Comparing the KPS, Harris and VAS scores pre- and
      postoperativelyat 1, 6, and 12 months, the combined therapy method was
      significantly effective in metastatic periacetabular tumor patients (P<0.05).
      CONCLUSIONS: Percutaneous cementoplasty with interstitial implantation of (125)I
      seeds is an effective treatment method for metastatic periacetabular tumor
      patients, providing tumor resistance, pain relief, increased bone stability, and
      improved quality of life for patients.

PMID- 23164343
TI  - Effect of autologous platelet-rich plasma on bone regeneration in mandibular
      fractures.
AB  - OBJECTIVES: The aim of this study was to assess the effect of autologous platelet
      rich plasma (PRP) on bone regeneration in mandibular fractures via a cone beam
      computed tomography (CBCT). PATIENTS AND METHODS: Twenty-four patients having
      parasymphyseal fractures participated in this study. They were randomly divided
      into two equal groups. Group A was treated by two titanium miniplates and screws
      plus local application of activated PRP along the fracture line, whereas group B
      was treated by the same bone plates and screws without application of PRP. The
      patients were recalled at 1 week, 3 and 6 months after surgery for clinical
      assessment and measuring the bone density via CBCT at a region of interest (ROI)
      including the fracture line. RESULTS: The mean values of the bone density
      measurements, in both groups, were higher at 3 and 6 months than 1 week after
      surgery. At 1 week after surgery, the values were 542 +/- 93 HU and 515 +/- 81 HU
      in group A and B, respectively. In group A, the mean value of bone density
      measurements was 728 +/- 58 HU (range 620-796 HU) at 3 months after surgery and
      it was 1024 +/- 188 HU (range 825-1490 HU) 6 months later. While in group B, the
      mean values of the bone density measurements at the ROI were 600 +/- 78 HU (range
      520-790 HU) and 756 +/- 53 HU (range 710-890 HU) at 3 and 6 months after surgery,
      respectively. The increase in the bone density measurements at 3 and 6 months
      after surgery was statistically significant only in group A (P = 0.0002 and P =
      0.0001, respectively). CONCLUSIONS: It can be concluded that direct application
      of the PRP along the fracture lines may enhance the bone regeneration in
      mandibular fractures.

PMID- 23164345
TI  - Prejudicial behavior: more closely linked to homophilic peer preferences than to
      trait bigotry.
AB  - We disagree with Dixon et al. by maintaining that prejudice is primarily rooted
      in aversive reactions toward out-group members. However, these reactions are not
      indicative of negative attributes, such as trait bigotry, but rather normative
      homophily for peers with similar perceived attributes. Cognitive biases such as
      stereotype threat perpetuate perceptions of inequipotential and subsequent
      discrimination, irrespective of individuals' personality characteristics.

PMID- 23164344
TI  - Occupational and leisure time physical activity in contrasting relation to
      ambulatory blood pressure.
AB  - BACKGROUND: While moderate and vigorous leisure time physical activities are well
      documented to decrease the risk for cardiovascular disease, several studies have
      demonstrated an increased risk for cardiovascular disease in workers with high
      occupational activity. Research on the underlying causes to the contrasting
      effects of occupational and leisure time physical activity on cardiovascular
      health is lacking. The aim of this study was to examine the relation of objective
      and self-report measures of occupational and leisure time physical activity with
      24-h ambulatory systolic blood pressure (BP). METHODS: Results for self-reported
      physical activity are based on observations in 182 workers (60% male, mean age 51
      years), while valid objective physical activity data were available in 151
      participants. The usual level of physical activity was assessed by 5 items from
      the Job Content Questionnaire (high physical effort, lifting heavy loads, rapid
      physical activity, awkward body positions and awkward positions of head or arms
      at work) and one item asking about the general level of physical activity during
      non-working time. On a regular working day, participants wore an ambulatory BP
      monitor and an accelerometer physical activity monitor during 24 h. Associations
      were examined by means of Analysis of Covariance. RESULTS: Workers with an
      overall high level of self-reported occupational physical activity as well as
      those who reported to often lift heavy loads at work had a higher mean systolic
      BP at work, at home and during sleep. However, no associations were observed
      between objectively measured occupational physical activity and BP. In contrast,
      those with objectively measured high proportion of moderate and vigorous leisure
      time physical activity had a significantly lower mean systolic BP during daytime,
      while no differences were observed according to self-reported level of leisure
      time physical activity. CONCLUSIONS: These findings suggest that workers
      reporting static occupational physical activities, unlike general physically
      demanding tasks characterized by dynamic movements of large muscle groups, are
      related to a higher daily systolic BP, while high objective levels of moderate
      and vigorous leisure time physical activity are related to lower daytime systolic
      BP. Ambulatory systolic BP may be a physiological explanatory factor for the
      contrasting effects of occupational and leisure time physical activity.

PMID- 23164347
TI  - [Apoptotic effect of coix polysaccharides on A549 lung cancer cells in vitro].
AB  - BACKGROUND AND OBJECTIVE: Coix seeds are commonly used in Traditional Chinese
      Medicine and ingested through daily diet. The aim of this study is to analyze the
      apoptotic effect of coix polysaccharides on A549 cells. METHODS: A fraction of
      polysaccharides was isolated from coix seeds and extracted by ethanol
      precipitation. The extract was then purified by dialysis and DEAE-52 ion-exchange
      chromatography. Cell viability was determined by the MTT assay. Cell morphology
      was observed by scanning electronic microscopy (SEM), and cell cycle was detected
      by flow cytometry (FCM). The relative quantities of caspase-3 and caspase-9 were
      determined by RT-PCR. RESULTS: Coix polysaccharides exerted remarkable inhibitory
      effects on A549 cell proliferation. Apoptotic bodies were observed by SEM.
      Apoptotic induction was also verified by DNA accumulation using propidium iodide
      nucleus staining in the S phase by flow cytometry, as well as by DNA
      fragmentation using the comet assay. Regarding the molecular mechanism of
      apoptosis induction, the gene expression of caspase-3 and caspase-9 increased
      after coix polysaccharide treatment. CONCLUSIONS: Polysaccharide fraction CP-1
      induced A549 cell apoptosis.

PMID- 23164348
TI  - [Experimental study on A549 cell death mediated by xenoantigen alpha-gal ?in
      human serum].
AB  - BACKGROUND AND OBJECTIVE: The absence of alpha-gal in humans is caused by the
      inactivity of alpha-1,3GT gene. However, humans have pre-existing and abundant
      anti-gal antibodies. Xenotransplantation procedures have indicated the high
      potential of introducing alpha-1,3GT gene to synthesize alpha-gal for cancer gene
      therapy by mimicking hyper-acute rejection. The aim of this study is to construct
      a lung cancer A549 cell line that expressed alpha-gal, and to observe the
      antitumor mechanisms mediated by human serum. METHODS: A549 cells were
      transfected with pEGFP-N1-GT plasmids constructed in a previous study. A stable
      transgenic cell line, A549-GT, was then selected and cultivated. The biological
      characteristics of A549-GT cells, including morphology and proliferation, were
      examined. alpha-1,3GT mRNA expression was detected by RT-PCR. Direct
      immunofluorescence staining and flow cytometry (FCM) were used to analyze the
      synthesis of alpha-gal in A549-GT. The binding of human serum IgM and C3 with
      A549-GT were also detected. RESULTS: alpha-1,3GT mRNA was expressed in A549-GT.
      Direct immunofluorescence staining and FCM indicated a high and stable alpha-gal
      expression rate in A549-GT. Compared with parental A549 cells, the biological
      characteristics of A549-GT were unaltered. alpha-Gal expression was not detected
      in the human fetal lung fibroblast cell line MRC-5 even though A549-GT and its
      culture medium were cultivated with the enzyme. Immunofluorescence staining and
      FCM also indicated abundant binding between A549-GT treated with human serum and
      IgM/C3. CONCLUSIONS: alpha-Gal expression in tumor cells by gene transduction can
      induce complement-dependent cytototic antitumor effects.

PMID- 23164349
TI  - [The effect of autophagy on the radioresistance of human adenocarcinoma A549 cell
      in hypoxia condition].
AB  - BACKGROUND AND OBJECTIVE: It has been proven that cancer cell autophagy can be
      induced by hypoxia. In addition, autophagy was correlated with radiosensitivity.
      Thus, regulating the autophagy signaling pathway is a potential treatment
      strategy. The aim of this study is to investigate the effects of combined
      autophagy inhibitor 3-methyladenine (3-MA) on the radiosensitivity of human
      adenocarcinoma A549 cells in hypoxia condition. METHODS: A549 cells were cultured
      in hypoxia condition, and then divided into two groups: hypoxia group and 3-MA
      plus hypoxia group. Electronic microscopy was used to detect autophagosome levels
      at different time points. The expression of LC3 was examined by Western blot. The
      proliferation activity of A549 cells after radiotherapy (0 Gy, 2 Gy, 4 Gy, 6 Gy,
      8 Gy, and 10 Gy) was determined with an MTT assay. RESULTS: Autophagosome
      formation and the LC3II/LC3I ratio increased under hypoxic conditions. After
      treatment with the autophagy inhibitor 3-MA, the quantity of autophagosomes and
      the LC3II/LC3I ratio decreased. The proliferative activity of the cells in the 3
      MA plus hypoxia group was remarkably lower than that in the hypoxia group after
      treatment with radiotherapy. CONCLUSIONS: The level of protective autophagy of
      A549 cells increased in hypoxia condition; thus, inhibiting autophagy improves
      the radiosensitivity of A549 cells.

PMID- 23164351
TI  - [Clinical role of F-18 FDG PET/CT in differentiating malignant and benign pleural
      effusion in patients with lung cancer].
AB  - BACKGROUND AND OBJECTIVE: Pleural effusions, a common feature among patients with
      lung cancer, should be differentiated into benign or malignant pleural effusions.
      F-18 fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT)
      is one of accurate diagnostic tool for differentiating benign from malignant
      disease and for mediastinal lymph node staging. We explored the clinical role of
      PET/CT for differentiating malignant pleural effusion from benign pleural
      effusion among patients with lung cancer. METHODS: We retrospectively reviewed
      the data from all patients with lung cancer and pleural effusion who underwent F
      18 FDG PET/CT. The PET/CT results were compared with the pathologic diagnosis or
      clinical follow-up. The sensitivity, specificity, positive predictive value,
      negative predictive value, and accuracy of PET/CT for detecting malignant pleural
      metastases were calculated. RESULTS: A total of 33 patients were enrolled. The
      sensitivity, specificity, positive predictive value, negative predictive value,
      and accuracy of PET/CT were 81.5%, 83.3%, 95.7%, 50.0%, and 81.8%, respectively,
      for detecting malignant pleural effusions lung cancer patients. CONCLUSIONS: Our
      results suggest that F-18 FDG PET/CT can play a significant role in diagnosing
      lung cancer patients with pleural diffusions, with low false-positive rate.
      However, negative findings under PET/CT should be confirmed through further
      tests.

PMID- 23164350
TI  - [Bioinformatic screening of key genes controlling the development and progression
      of lung cancer].
AB  - BACKGROUND AND OBJECTIVE: Lung cancer is the most common cancer in the world. The
      gene expression profiling of lung cancer has been extensively investigated.
      However, only a few studies have identified the possible pathways and significant
      genes related to lung cancer. The aim of this study is to explore the large
      number of lung cancer-related microarray datasets and identify the crucial genes
      that can benefit the understanding of the progression and development of this
      disease. METHODS: To identify the genes that effected lung cancer at the mRNA
      level, gene set enrichment analysis was used to analyze six selected gene
      expression datasets. RESULTS: Among the six gene expression datasets, 3 up
      regulated and 26 down-regulated pathways were found by gene set enrichment
      analysis. We found 11 significant genes with P < 0.05 from the results of tight
      junction meta-analysis of the six data sets. CONCLUSIONS: The tight junction
      pathway plays an important role in the study of the occurrence and development of
      lung cancer. Significant genes within the pathways will be further discussed in
      future studies.

PMID- 23164352
TI  - [Prognostic value of lymphangiogenesis and lymphatic vessel invasion in non-small
      cell lung cancer].
AB  - BACKGROUND AND OBJECTIVE: Studies have shown that tumor metastasis in a variety
      of tumors is associated with lymphangiogenesis and lymphatic vessel invasion
      (LVI). Tumor metastasis is an important factor that affects the prognosis of
      patients. The aim of this study is to determine the prognostic value of
      lymphangiogenesis and LVI in non-small cell lung cancer (NSCLC). METHODS: We
      marked the endothelial cells of lymph vessels in lymphangiogenesis with specific
      monoclonal antibody D2-40. Immunohistochemistry was used to detect the expression
      of lymphangiogenesis and LVI in 79 cases of stage I-III NSCLC. RESULTS: The
      intratumoral lymphatic vessel density (ITLVD) was significantly higher in
      patients with N2 disease than those with N0 disease (P=0.015). The ITLVD was
      significantly higher in patients with LVI+ than that in those with LVI- (P =
      0.009). The ITLVD was also remarkably higher in poorly differentiated tumors than
      that in highly differentiated ones (P = 0.007). The ITLVD was remarkably higher
      in adenocarcinoma than that in squamous cell carcinomas (P = 0.025). Kaplan-Meier
      revealed that the survival rates of patients with higher ITLVD were remarkably
      poorer than those with lower ITLVD (P = 0.007). Thus, the ITLVD is an important
      prognostic factor of NSCLC. The peritumoral lymphatic vessel density is not
      correlated with the prognosis. CONCLUSIONS: The ITLVD level is an important
      prognostic factor of NSCLC.

PMID- 23164353
TI  - [Multiple focal pure ground-glass opacities on HRCT images: clinical significance
      in patients with lung cancer].
AB  - BACKGROUND AND OBJECTIVE: Some cases of lung cancer in addition to a primary
      tumor are associated with multiple pure ground-glass opacities (pGGOs). The
      objective of this study is to evaluate the clinical significance of multiple
      pGGOs on CT images of patients with lung cancer. The number, size, distribution,
      and morphological characteristics of the pGGOs were evaluated. Serial changes in
      pGGOs that were not surgically resected were analyzed at follow-up CT. METHODS:
      The cases of 25 patients with proven lung cancer and associated multiple pGGOs on
      CT images were retrospectively reviewed. RESULTS: In total, 207 pGGOs were
      detected. The size of the opacities ranged from 2 mm to 31 mm in largest
      diameter. Lung cancer and pGGOs were seen in the same lobe and/or in other lobes.
      Of the lesions, 183 (88.4%) had a round shape or well-defined border.
      Histological findings were obtained for 17 lesions representing 87 pGGOs that
      were surgically resected, namely, 13 atypical adenomatous hyperplasias, 3
      bronchioloalveolar carcinomas, and 1 focal fibrosis. Of the 120 pGGOs followed up
      with CT for a median duration of 61.5 months, 113 (94.2%) retained their size, 1
      decreased in size, and 6 disappeared. CONCLUSIONS: The size of most pGGOs
      associated with lung cancer did not change during the follow-up period. Most of
      the lesions histologically diagnosed were atypical adenomatous hyperplasias or
      bronchioloalveolar carcinomas. The results justify the therapeutic strategy of
      resecting the primary tumor without therapeutic intervention in the remaining
      pGGOs.

PMID- 23164354
TI  - [Advances of treatment of small cell lung cancer in 2012 American Society of
      Clinical Oncology Annual Meeting].

PMID- 23164355
TI  - Prejudice in context departs from attitudes toward groups.
AB  - The analysis offered by Dixon et al. fails to acknowledge that the attitudes that
      drive prejudice are attitudes that are constructed in particular contexts. These
      attitudes (e.g., toward men as childcare workers) can diverge strongly from
      attitudes toward the group in general. Social change is thus best achieved
      through challenging the requirements of roles and by changing group stereotypes.

PMID- 23164356
TI  - Involvement of formyl peptide receptors in receptor for advanced glycation end
      products (RAGE)--and amyloid beta 1-42-induced signal transduction in glial
      cells.
AB  - BACKGROUND: Recent studies suggest that the chemotactic G-protein-coupled
      receptor (GPCR) formyl-peptide-receptor-like-1 (FPRL1) and the receptor-for
      advanced-glycation-end-products (RAGE) play an important role in the inflammatory
      response involved in neurodegenerative disorders such as Alzheimer's disease
      (AD).Therefore, the expression and co-localisation of mouse formyl peptide
      receptor (mFPR) 1 and 2 as well as RAGE in an APP/PS1 transgenic mouse model
      using immunofluorescence and real-time RT-PCR were analysed. The involvement of
      rat or human FPR1/FPRL1 (corresponds to mFPR1/2) and RAGE in amyloid-beta 1-42
      (Abeta1-42)-induced signalling were investigated by extracellular signal
      regulated kinase 1/2 (ERK1/2) phosphorylation. Furthermore, the cAMP level in
      primary rat glial cells (microglia and astrocytes) and transfected HEK 293 cells
      was measured. Formyl peptide receptors and RAGE were inhibited by a small
      synthetic antagonist WRW4 and an inactive receptor variant delta-RAGE, lacking
      the intracytoplasmatic domains. RESULTS: We demonstrated a strong increase of
      mFPR1/2 and RAGE expression in the cortex and hippocampus of APP/PS1 transgenic
      mice co-localised to the glial cells. In addition, the Abeta1-42-induced signal
      transduction is dependant on FPRL1, but also on FPR1. For the first time, we have
      shown a functional interaction between FPRL1/FPR1 and RAGE in RAGE ligands S100B-
      or AGE-mediated signalling by ERK1/2 phosphorylation and cAMP level measurement.
      In addition a possible physical interaction between FPRL1 as well as FPR1 and
      RAGE was shown with co-immunoprecipitation and fluorescence microscopy.
      CONCLUSIONS: The results suggest that both formyl peptide receptors play an
      essential role in Abeta1-42-induced signal transduction in glial cells. The
      interaction with RAGE could explain the broad ligand spectrum of formyl peptide
      receptors and their important role for inflammation and the host defence against
      infections.

PMID- 23164357
TI  - Access to commercial destinations within the neighbourhood and walking among
      Australian older adults.
AB  - BACKGROUND: Physical activity, particularly walking, is greatly beneficial to
      health; yet a sizeable proportion of older adults are insufficiently active. The
      importance of built environment attributes for walking is known, but few studies
      of older adults have examined neighbourhood destinations and none have
      investigated access to specific, objectively-measured commercial destinations and
      walking. METHODS: We undertook a secondary analysis of data from the Western
      Australian state government's health surveillance survey for those aged 65-84
      years and living in the Perth metropolitan region from 2003-2009 (n = 2,918).
      Individual-level road network service areas were generated at 400 m and 800 m
      distances, and the presence or absence of six commercial destination types within
      the neighbourhood service areas identified (food retail, general retail, medical
      care services, financial services, general services, and social infrastructure).
      Adjusted logistic regression models examined access to and mix of commercial
      destination types within neighbourhoods for associations with self-reported
      walking behaviour. RESULTS: On average, the sample was aged 72.9 years (SD =
      5.4), and was predominantly female (55.9%) and married (62.0%). Overall, 66.2%
      reported some weekly walking and 30.8% reported sufficient walking (>=150
      min/week). Older adults with access to general services within 400 m (OR = 1.33,
      95% CI = 1.07-1.66) and 800 m (OR = 1.20, 95% CI = 1.02-1.42), and social
      infrastructure within 800 m (OR = 1.19, 95% CI = 1.01-1.40) were more likely to
      engage in some weekly walking. Access to medical care services within 400 m (OR =
      0.77, 95% CI = 0.63-0.93) and 800 m (OR = 0.83, 95% CI = 0.70-0.99) reduced the
      odds of sufficient walking. Access to food retail, general retail, financial
      services, and the mix of commercial destination types within the neighbourhood
      were all unrelated to walking. CONCLUSIONS: The types of neighbourhood commercial
      destinations that encourage older adults to walk appear to differ slightly from
      those reported for adult samples. Destinations that facilitate more social
      interaction, for example eating at a restaurant or church involvement, or provide
      opportunities for some incidental social contact, for example visiting the
      pharmacy or hairdresser, were the strongest predictors for walking among seniors
      in this study. This underscores the importance of planning neighbourhoods with
      proximate access to social infrastructure, and highlights the need to create
      residential environments that support activity across the life course.

PMID- 23164359
TI  - Mean atomic number quantitative assessment in backscattered electron imaging.
AB  - A method for obtaining quantitative mean atomic number images in a scanning
      electron microscope for different kinds of samples has been developed. The
      backscattered electron signal is monotonically increasing with the mean atomic
      number Z, and accordingly Z can be given as a function of the image gray levels.
      From results obtained from Monte Carlo simulations, an exponential function is
      fitted to convert the backscattered registered gray levels into a Z image map.
      Once this fitting was performed, the reproducibility of the Z determination was
      checked through the acquisition of backscattered electron images from metal and
      mineral standards. The developed method can be applied to any unknown sample,
      always controlling the experimental conditions, as shown here for a thin section
      of a rock in which several unknown mineral phases are present; the results
      obtained herein are compared to quantitative assessments performed with X-ray
      spectra from each mineral phase.

PMID- 23164358
TI  - Can cognitive deficits facilitate differential diagnosis between at-risk mental
      state for psychosis and depressive disorders?
AB  - AIM: Many studies have provided evidence of cognitive deficits in individuals in
      an 'At Risk Mental State' (ARMS) for psychosis, which makes neuropsychology
      potentially useful in the early detection of psychosis. As depression is an
      important differential diagnosis in prodromal states of psychosis, the
      specificity of neurocognitive deficits in ARMS individuals as compared with non
      psychotic depressive disorders is investigated. METHODS: Neurocognitive
      performance of four groups was analysed: 22 ARMS individuals with later
      transition to psychosis (ARMS-T), 25 ARMS individuals without later transition to
      psychosis (ARMS-NT), 34 controls with depressive disorders and 76 healthy
      controls. The subjects were assessed with a neurocognitive test battery covering
      the domains' intelligence, executive function and attention/ working memory.
      MANOVAs, ANOVAs and Tukey's tests were applied after adjustment for confounding
      factors. RESULTS: ARMS-T showed significant cognitive deficits in working memory
      and in certain executive function tasks compared with healthy controls as well as
      with controls with depression. Controls with depression were only impaired in
      time per move in the tower of Hanoi test when compared with healthy controls.
      CONCLUSIONS: The psychosis prodrome seems to be associated with cognitive
      deficits in the domains of working memory and executive function. In contrast,
      depressive patients showed no cognitive deficits, but slowing in one executive
      function task. Neurocognitive testing might therefore contribute to the
      differential diagnosis between prodromal psychosis and depressive disorders.

PMID- 23164360
TI  - Association of IL12B polymorphisms with susceptibility to Graves ophthalmopathy
      in a Taiwan Chinese population.
AB  - BACKGROUND: Interleukin 12B (IL12B) gene polymorphisms have been linked to
      several inflammatory diseases, but their role in the development of Graves
      ophthalmopathy (GO) in Graves disease (GD) patients is unclear. The purpose of
      this study was to investigate the disease association of IL12B single nucleotide
      polymorphisms (SNPs). METHODS: A Taiwan Chinese population comprising 200 GD
      patients with GO and 271 GD patients without GO was genotyped using an allele
      specific extension and ligation method. Hardy-Weinberg equilibrium was estimated
      using the chi-square test. Allele and genotype frequencies were compared between
      GD patients with and without GO using the chi-square test. RESULTS: The genotype
      and allele frequencies of examined SNPs did not differ between GD patients with
      and without GO. Although the genotype distribution remained nonsignificant in the
      sex-stratified analyses, the frequency of the T allele at SNP rs1003199 was
      significantly higher in patients with GO in the male cohort (P = 6.00 * 10(-3)).
      In addition, haplotypes of IL12B may be used to predict the risk of GO (P = 1.70
      * 10(-2)); however, we could not prove the statistical significance of analysis
      after applying the Bonferroni correction. CONCLUSIONS: Our results provide new
      information that the examined IL12B gene polymorphisms may be associated with
      susceptibility to GO in the Taiwan Chinese population in a sex-specific manner.
      This conclusion requires further investigation.

PMID- 23164361
TI  - Nitric oxide delivery via a permeable balloon catheter inhibits neointimal growth
      after arterial injury.
AB  - BACKGROUND: Neointimal hyperplasia limits the longevity of vascular
      interventions. Nitric oxide (NO) is well known to inhibit neointimal hyperplasia.
      However, delivery of NO to the vasculature is challenging. Our study aims to
      evaluate the efficacy of delivering NO to the site of injury using a permeable
      balloon catheter. Our hypothesis is that ultra-short duration NO delivery using a
      permeable balloon catheter will inhibit neointimal hyperplasia. MATERIALS AND
      METHODS: Ten-week-old male Sprague-Dawley rats underwent carotid artery balloon
      injury. Groups included: (1) control, (2) injury, (3) injury + periadventitial
      NO, and (4) injury + endoluminal NO via permeable balloon catheter. The catheter
      was inflated to 5 atm pressure for 5 min. Arteries were harvested 2 wk following
      injury. Morphometric assessment for neointimal hyperplasia and
      immunohistochemical staining for inflammatory markers were performed. RESULTS:
      Injury increased neointimal hyperplasia compared with control (intima/media area
      [I/M] ratio 1.07 versus 0.11, respectively, P < 0.001). Periadventitial delivery
      of NO reduced the I/M area ratio compared with injury alone (55% decrease, P <
      0.001). Endoluminal delivery of NO also reduced the I/M area ratio compared with
      injury alone (65% decrease; P < 0.001). Both endoluminal and periadventitial NO
      affected the I/M ratio by reducing the intimal area (64% and 46%, respectively, P
      < 0.001) whereas neither affected the medial area. Periadventitial NO delivery
      increased lumen area (P < 0.05), whereas endoluminal NO delivery increased
      circumference (P < 0.05). Periadventitial NO delivery inhibited macrophage
      intimal infiltration compared with injury alone (P < 0.05). CONCLUSIONS: These
      data demonstrate that short-duration endoluminal NO delivery via permeable
      balloon catheters inhibits neointimal hyperplasia following arterial
      interventions. Endoluminal delivery of NO could become a focus for future
      clinical interventions.

PMID- 23164363
TI  - Special section: 14th International Meeting on Recent Developments in
      Pharmaceutical Analysis (RDPA 2011), 21-24 September 2011, Pavia, Italy. Preface.

PMID- 23164362
TI  - Differential effect of zoledronic acid on human vascular smooth muscle cells.
AB  - INTRODUCTION: The activation of human vascular smooth muscle cell proliferation,
      adhesion and migration is essential for intimal hyperplasia formation. These
      experiments were designed to test whether zoledronic acid (ZA) would modulate
      indices of human smooth muscle cell activation, exert differential effects on
      proliferating versus quiescent cells, and determine whether these effects were
      dependent on GTPase binding proteins prenylation. ZA was chosen for testing in
      these experiments because it is clinically used in humans with cancer, and has
      been shown to modulate rat smooth muscle cell proliferation and migration.
      METHODS: Human aortic smooth muscle cells (HASMC) were cultured under either
      proliferating or growth arrest (quiescent) conditions in the presence or absence
      of ZA for 48 hours, whereupon the effect of ZA on HASMC proliferation, cellular
      viability, metabolic activity, and membrane integrity were compared. In addition,
      the effect of ZA on adhesion and migration were assessed in proliferating cells.
      The effect of increased concentration of ZA on the mevalonate pathway and
      genomic/cellular stress related poly-adenosine diphosphate ribose polymerase
      enzyme activity were assessed using the relative prenylation of Rap-1A/B protein
      and the formation of poly adenosine diphosphate-ribosylated protein,
      respectively. RESULTS: There was a dose dependent inhibition of cellular
      proliferation, adhesion and migration following ZA treatment. ZA treatment
      decreased indices of cellular viability and significantly increased membrane
      injury in proliferating versus quiescent cells. This was correlated with the
      appearance of unprenylated Rap-1A protein and dose dependent down regulation of
      activity. CONCLUSIONS: These data suggest that ZA is effective in inhibiting
      HASMC proliferation, adhesion, and migration, which coincide with the appearance
      of unprenylated RAP-1A/B protein, thereby suggesting that the mevalonate pathway
      may play a role in the inhibition of HASMC activation.

PMID- 23164364
TI  - From extreme emotions to extreme actions: explaining non-normative collective
      action and reconciliation.
AB  - A key argument of Dixon et al. in the target article is that prejudice reduction
      through intergroup contact and collective action work in opposite ways. We argue
      for a complementary approach focusing on extreme emotions to understand why
      people turn to nonnormative collective action and to understand when and under
      what conditions extreme emotions may influence positive effects of contact on
      reconciliation.

PMID- 23164365
TI  - Emerging role of the ubiquitin proteasome system in the control of shoot apical
      meristem function(f).
AB  - The shoot apical meristem (SAM) is a population of undifferentiated cells at the
      tip of the shoot axis that establishes early during plant embryogenesis and gives
      rise to all shoot organs throughout the plant's life. A plethora of different
      families of transcription factors (TFs) play a key role in establishing the
      equilibrium between cell differentiation and stem cell maintenance in the SAM.
      Fine tuning of these regulatory proteins is crucial for a proper and fast SAM
      response to environmental and hormonal cues, and for development progression. One
      effective way to rapidly inactivate TFs involves regulated proteolysis by the
      ubiquitin/26S proteasome system (UPS). However, a possible role of UPS-dependent
      protein degradation in the regulation of key SAM TFs has not been thoroughly
      investigated. Here, we summarize recent evidence supporting a role for the UPS in
      SAM maintenance and function. We integrate this survey with an in silico analysis
      of publicly-available microarray databases which identified ubiquitin ligases
      that are expressed in specific areas within the SAM, suggesting that they may
      regulate or act downstream of meristem-specific factors.

PMID- 23164366
TI  - Sustained employability of workers in a production environment: design of a
      stepped wedge trial to evaluate effectiveness and cost-benefit of the POSE
      program.
AB  - BACKGROUND: Sustained employability and health are generating awareness of
      employers in an aging and more complex work force. To meet these needs, employers
      may offer their employees health surveillance programs, to increase opportunities
      to work on health and sustained employability. However, evidence for these health
      surveillance programs is lacking. The FLESH study (Functional Labour Evaluation
      for Sustained Health and employment) was developed to evaluate a comprehensive
      workers' health promotion program on its effectiveness, cost-benefit, and process
      of the intervention. METHODS: The study is designed as a cluster randomised
      stepped wedge trial with randomisation at company plant level and is carried out
      in a large meat processing company. Every contracted employee is offered the
      opportunity to participate in the POSE program (Promotion Of Sustained
      Employability). The main goals of the POSE program are 1) providing employee's
      insight into their current employability and health status, 2) offering
      opportunities to improve employability and decrease health risks and 3) improving
      employability and health sustainably in order to keep them healthy at work. The
      program consists of a broad assessment followed by a counselling session and, if
      needed, a tailored intervention. Measurements will be performed at baseline and
      will be followed up at 20, 40, 60, 80, 106 and 132 weeks. The primary outcome
      measures are work ability, productivity and absenteeism. Secondary outcomes
      include health status, vitality, and psychosocial workload. A cost-benefit study
      will be conducted from the employers' perspective. A process evaluation will be
      conducted and the satisfaction of employer and employees with the program will be
      assessed. DISCUSSION: This study provides information on the effectiveness of the
      POSE program on sustained employment. When the program proves to be effective,
      employees benefit by improved work ability, and health. Employers benefit from
      healthier employees, reduced sick leave (costs) and higher productivity. The
      study can expose key elements for a successful implementation and execution of
      the POSE program and may serve as an example to other companies inside and
      outside the industry. TRIAL REGISTRATION: The trial is registered at the Dutch
      Trial Register (http://www.trialregister.nl): NTR3445.

PMID- 23164367
TI  - Estimating relative abundances of proteins from shotgun proteomics data.
AB  - BACKGROUND: Spectral counting methods provide an easy means of identifying
      proteins with differing abundances between complex mixtures using shotgun
      proteomics data. The crux spectral-counts command, implemented as part of the
      Crux software toolkit, implements four previously reported spectral counting
      methods, the spectral index (SI(N)), the exponentially modified protein abundance
      index (emPAI), the normalized spectral abundance factor (NSAF), and the
      distributed normalized spectral abundance factor (dNSAF). RESULTS: We compared
      the reproducibility and the linearity relative to each protein's abundance of the
      four spectral counting metrics. Our analysis suggests that NSAF yields the most
      reproducible counts across technical and biological replicates, and both SI(N)
      and NSAF achieve the best linearity. CONCLUSIONS: With the crux spectral-counts
      command, Crux provides open-source modular methods to analyze mass spectrometry
      data for identifying and now quantifying peptides and proteins. The C++ source
      code, compiled binaries, spectra and sequence databases are available at
      http://noble.gs.washington.edu/proj/crux-spectral-counts.

PMID- 23164368
TI  - Coping styles of individuals at clinical high risk for developing psychosis.
AB  - AIM: There is a wealth of evidence suggesting that patients with schizophrenia
      tend to respond to life stressors using less effective coping skills, which are
      in turn related to poor outcome. However, the contribution of coping strategies
      to outcome in youth at clinical high risk (CHR) for developing psychosis has not
      been investigated. METHODS: This longitudinal study followed CHR youth over a 12
      month period, using the Brief COPE questionnaire. CHR subjects (n = 88) were
      compared at baseline with a healthy control sample (n = 53), and then mixed
      models were used to explore the relationship of coping strategies to clinical and
      psychosocial outcomes in CHR subjects over time (n = 102). RESULTS: Cross
      sectional analyses revealed that, in comparison with healthy controls, CHR youth
      reported using more maladaptive coping strategies (P < 0.001) and fewer adaptive
      coping strategies (P < 0.01). Longitudinal analyses within the CHR group showed
      significant decreases in maladaptive coping and symptom severity over time, with
      corresponding improvements in social and role functioning. Adaptive coping was
      associated with better concurrent social functioning and less severe
      symptomatology (both P < 0.001). Over time, more maladaptive coping was
      associated with more severe positive and negative symptoms (both P < 0.005).
      CONCLUSIONS: Youth at risk for psychosis report using fewer adaptive and more
      maladaptive coping strategies relative to healthy controls. Over 1-year follow
      up, more adaptive coping styles are associated with less severe clinical
      symptomatology and better social functioning. These findings suggest that
      teaching adaptive coping styles may be an important target for intervention in
      youth at high risk for psychosis.

PMID- 23164369
TI  - Region-specific effects on BDNF expression after contingent or non-contingent
      cocaine i.v. self-administration in rats.
AB  - Brain-derived neurotrophic factor (BDNF) dynamic changes were investigated in the
      medial prefrontal cortex (mPFC) and nucleus accumbens (NAc) during use and the
      early phases of cocaine abstinence after 14 sessions (2 h self-administration/d;
      0.25 mg/0.1 ml.6 s infusion) by employing a 'yoked control-operant paradigm'. The
      effect on BDNF was region-specific and dependent on the withdrawal time. In the
      NAc, BDNF protein levels increased immediately after the last self-administration
      session, with a larger increase in passively cocaine-exposed rats. In the mPFC,
      BDNF expression was elevated 24 h after the last self-administration session,
      independently of how the drug was encountered. No changes were found in NAc and
      mPFC 7 d after the last self-administration session. Analysis of transcript
      levels in the mPFC indicated that action on exon I might contribute to BDNF's
      cortical induction. These findings indicate a finely tuned modulation of BDNF
      expression during use and early phases of cocaine abstinence.

PMID- 23164370
TI  - Corticolimbic brain reactivity to social signals of threat before and after
      sertraline treatment in generalized social phobia.
AB  - BACKGROUND: Generalized social phobia (gSP), also known as generalized social
      anxiety disorder, is characterized by excessive fear of scrutiny by others and
      pervasive avoidance of social interactions. Pathophysiologic models of gSP
      implicate exaggerated reactivity of the amygdala and insula in response to social
      evaluative threat, making them plausible targets for treatment. Although
      selective serotonin reuptake inhibitor (SSRI) treatment is known to be an
      effective treatment, little is known about the mechanism through which these
      agents exert their anxiolytic effects at a brain level in gSP. METHODS: We
      acquired functional magnetic resonance imaging data of brain response to social
      signals of threat (fearful/angry faces) in 21 gSP patients before and after they
      completed 12 weeks of open-label treatment with the SSRI sertraline. For
      comparison, 19 healthy control (HC) subjects also underwent two functional
      magnetic resonance imaging scans, 12 weeks apart. RESULTS: Whole-brain voxelwise
      analysis of variance revealed significant Group*Time interactions in the amygdala
      and the ventral medial prefrontal cortex. Follow-up analyses showed that
      treatment in gSP subjects reduced amygdala reactivity to fearful faces (which was
      exaggerated relative to HCs before treatment) and enhanced ventral medial
      prefrontal cortex activation to angry faces (which was attenuated relative to HCs
      before treatment). However, these brain changes were not significantly related to
      social anxiety symptom improvement. CONCLUSIONS: SSRI treatment response in gSP
      is associated with changes in a discrete limbic-paralimbic brain network,
      representing a neural mechanism through which SSRIs may exert their actions.

PMID- 23164371
TI  - Are attitudes the problem, and do psychologists have the answer? Relational
      cognition underlies intergroup relations.
AB  - The focus on negative attitudes toward other groups has led to a dichotomy
      between the prejudice reduction and the collective action approach. To solve the
      resulting problems identified by Dixon et al., we suggest analyzing the
      psychological processes underlying the construction of relationships (and their
      alternatives) between own and other groups.

PMID- 23164372
TI  - Regulated protein aggregation: stress granules and neurodegeneration.
AB  - The protein aggregation that occurs in neurodegenerative diseases is classically
      thought to occur as an undesirable, nonfunctional byproduct of protein
      misfolding. This model contrasts with the biology of RNA binding proteins, many
      of which are linked to neurodegenerative diseases. RNA binding proteins use
      protein aggregation as part of a normal regulated, physiological mechanism
      controlling protein synthesis. The process of regulated protein aggregation is
      most evident in formation of stress granules. Stress granules assemble when RNA
      binding proteins aggregate through their glycine rich domains. Stress granules
      function to sequester, silence and/or degrade RNA transcripts as part of a
      mechanism that adapts patterns of local RNA translation to facilitate the stress
      response. Aggregation of RNA binding proteins is reversible and is tightly
      regulated through pathways, such as phosphorylation of elongation initiation
      factor 2alpha. Microtubule associated protein tau also appears to regulate stress
      granule formation. Conversely, stress granule formation stimulates pathological
      changes associated with tau. In this review, I propose that the aggregation of
      many pathological, intracellular proteins, including TDP-43, FUS or tau, proceeds
      through the stress granule pathway. Mutations in genes coding for stress granule
      associated proteins or prolonged physiological stress, lead to enhanced stress
      granule formation, which accelerates the pathophysiology of protein aggregation
      in neurodegenerative diseases. Over-active stress granule formation could act to
      sequester functional RNA binding proteins and/or interfere with mRNA transport
      and translation, each of which might potentiate neurodegeneration. The
      reversibility of the stress granule pathway also offers novel opportunities to
      stimulate endogenous biochemical pathways to disaggregate these pathological
      stress granules, and perhaps delay the progression of disease.

PMID- 23164373
TI  - A comparison of chlorhexidine-alcohol versus povidone-iodine for eliminating skin
      flora before genitourinary prosthetic surgery: a randomized controlled trial.
AB  - PURPOSE: We defined the relevant skin flora during genitourinary prosthetic
      surgery, evaluated the safety of chlorhexidine-alcohol for use on the male
      genitalia and compared chlorhexidine-alcohol to povidone-iodine in decreasing the
      rate of positive bacterial skin cultures at the surgical skin site before
      prosthetic device implantation. MATERIALS AND METHODS: In this single
      institution, prospective, randomized, controlled study we evaluated 100
      consecutive patients undergoing initial genitourinary prosthetic implantation.
      Patients were randomized to a standard skin preparation with povidone-iodine or
      chlorhexidine-alcohol. Skin cultures were obtained from the surgical site before
      and after skin preparation. RESULTS: A total of 100 patients were randomized,
      with 50 in each arm. Pre-preparation cultures were positive in 79% of the
      patients. Post-preparation cultures were positive in 8% in the chlorhexidine
      alcohol group compared to 32% in the povidone-iodine group (p = 0.0091).
      Coagulase-negative staphylococci were the most commonly isolated organisms in
      post-preparation cultures in the povidone-iodine group (13 of 16 patients) as
      opposed to propionibacterium in the chlorhexidine-alcohol group (3 of 4
      patients). Clinical complications requiring additional operations or device
      removal occurred in 6 patients (6%) with no significant difference between the 2
      groups. No urethral or genital skin complications occurred in either group.
      CONCLUSIONS: Chlorhexidine-alcohol was superior to povidone-iodine in eradicating
      skin flora at the surgical skin site before genitourinary prosthetic
      implantation. There does not appear to be any increased risk of urethral or
      genital skin irritation with the use of chlorhexidine compared to povidone
      iodine. Chlorhexidine-alcohol appears to be the optimal agent for skin
      preparation before genitourinary prosthetic procedures.

PMID- 23164374
TI  - Editorial comment.

PMID- 23164375
TI  - Usefulness of R.E.N.A.L. nephrometry scoring system for predicting outcomes and
      complications of percutaneous ablation of 751 renal tumors.
AB  - PURPOSE: We applied the R.E.N.A.L. (radius, exophytic/endophytic, nearness to
      collecting system or sinus, anterior/posterior and location relative to polar
      lines) nephrometry scoring system to renal tumors treated with percutaneous
      ablation to determine whether this score is associated with oncological outcomes
      and complications. MATERIALS AND METHODS: A total of 751 renal tumors were
      treated at 679 percutaneous ablation sessions in 627 patients at our institution
      between 2000 and 2012. Of these renal masses 430 (57%) were treated with
      cryoablation and the remaining 321 were treated with radio frequency ablation.
      R.E.N.A.L. tumor scores were analyzed to determine the association of the score
      with ablation treatment outcomes and complications according to Clavien criteria.
      RESULTS: The mean +/- SD R.E.N.A.L. nephrometry score of all ablated tumors was
      6.7 +/- 1.9. Those treated with cryoablation had higher scores than those treated
      with radio frequency ablation (mean 7.2 +/- 1.9 vs 6.1 +/- 1.8, p <0.001). We
      identified a total of 28 local treatment failures (3.7%) in the 751 tumors during
      a mean computerized tomography/magnetic resonance imaging followup of 27.9 +/-
      27.8 months. There was a significant association between R.E.N.A.L. nephrometry
      score and local treatment failure. Mean nephrometry score was 7.6 +/- 2.2 vs 6.7
      +/- 1.9 for tumors with vs without local treatment failure (p <0.001). Of the 679
      ablation treatments 38 (5.6%) major (grade 3 or greater) patient complications
      occurred. There was a significant association between R.E.N.A.L. nephrometry
      score and major complications. Patients with vs without a major complication had
      a mean nephrometry score of 8.1 +/- 2.0 vs 6.8 +/- 1.9 (p <0.001). CONCLUSIONS:
      The R.E.N.A.L. nephrometry scoring system predicts treatment efficacy and
      complications following percutaneous renal ablation.

PMID- 23164376
TI  - Severe genitourinary toxicity following radiation therapy for prostate cancer-
      how long does it last?
AB  - PURPOSE: Radiation therapy is a common treatment for localized prostate cancer
      but long-term data are sparse on treatment related toxicity compared to
      observation. We evaluated the time course of grade 2-4 genitourinary toxicities
      in men treated with primary radiation or observation for T1-T2 prostate cancer.
      MATERIALS AND METHODS: We performed a population based cohort study using
      Medicare claims data linked to SEER (Surveillance, Epidemiology and End Results)
      data. Cumulative incidence functions for time to first genitourinary event were
      calculated based on the competing risks model with death before any genitourinary
      event as a competing event. The generalized estimating equation method was used
      to evaluate the risk ratios of recurrent events. RESULTS: Of the study patients
      60,134 received radiation therapy and 25,904 underwent observation. The adjusted
      risk ratio for genitourinary toxicity was 2.49 (95% CI 2.00-3.11) for 10 years
      and thereafter. Patients who had required prior procedures for
      obstruction/stricture, including transurethral prostate resection, before
      radiation therapy were at significantly increased risk for genitourinary toxicity
      (risk ratio 2.78, 95% CI 2.56-2.94). CONCLUSIONS: This study demonstrates that
      the increased risk of grade 2-4 genitourinary toxicities attributable to
      radiation therapy persists 10 years after treatment and thereafter. Patients who
      required prior procedures for obstruction/stricture were at higher risk for
      genitourinary toxicity than those without these preexisting conditions.

PMID- 23164377
TI  - Prostate total tumor extent versus index tumor extent--which is predictive of
      biochemical recurrence following radical prostatectomy?
AB  - PURPOSE: It is controversial whether tumor extent in radical prostatectomies
      predicts biochemical recurrence following surgery. We compared the predictive
      value of total tumor extent vs dominant nodule (index tumor) extent. MATERIALS
      AND METHODS: A mean of 32 paraffin blocks was processed from prostate surgical
      specimens step sectioned at 3 to 5 mm intervals from 300 patients treated with
      radical retropubic prostatectomy. Each transverse section was subdivided into 2
      anterolateral and 2 posterolateral quadrants. Tumor extent was evaluated by a
      semiquantitative point count method. Dominant nodule extent was recorded as the
      maximal number of positive points of the largest single focus of cancer in the
      quadrants. Time to biochemical recurrence was analyzed by Kaplan-Meier product
      limit analysis. Prediction of shorter time to biochemical recurrence was
      determined by univariate and multivariate Cox proportional hazards models.
      RESULTS: Except for age and race, total and index tumor extent was significantly
      associated with higher preoperative prostate specific antigen, clinical stage T2,
      pathological stage greater than T2, positive surgical margins and higher radical
      prostatectomy Gleason score. Total and index tumor extent was significantly
      associated with time to biochemical recurrence in Kaplan-Meier estimates. Total
      and index tumor extent significantly predicted shorter time to biochemical
      recurrence on univariate analysis but only index tumor extent was an independent
      predictor of time to biochemical recurrence on multivariate analysis.
      CONCLUSIONS: The study indicates that any tumor extent estimate in surgical
      specimens should be related to the dominant nodule (index tumor) and not to total
      tumor extent.

PMID- 23164378
TI  - Editorial comment.

PMID- 23164379
TI  - Multiparametric ultrasound of the prostate: adding contrast enhanced ultrasound
      to real-time elastography to detect histopathologically confirmed cancer.
AB  - PURPOSE: We prospectively assessed whether a combined approach of real-time
      elastography and contrast enhanced ultrasound would improve prostate cancer
      visualization. MATERIAL AND METHODS: Between June 2011 and January 2012, 100
      patients with biopsy proven prostate cancer underwent preoperative transrectal
      multiparametric ultrasound combining real-time elastography and contrast enhanced
      ultrasound. After initial elastographic screening for suspicious lesions, defined
      as blue areas with decreased tissue strain, each lesion was allocated to the
      corresponding prostate sector. The target lesion was defined as the largest
      cancer suspicious area. Perfusion was monitored after intravenous injection of
      contrast agent. Target lesions were examined for hypoperfusion, normoperfusion or
      hyperperfusion. Imaging results were correlated with final pathological
      evaluation on whole mount slides after radical prostatectomy. RESULTS: Of 100
      patients 86 were eligible for final analysis. Real-time elastography detected
      prostate cancer with 49% sensitivity and 73.6% specificity. Histopathology
      confirmed malignancy in 56 of the 86 target lesions (65.1%). Of these 56 lesions
      52 (92.9%) showed suspicious perfusion, including hypoperfusion in 48.2% and
      hyperperfusion in 48.2%, while only 4 (7.1%) showed normal perfusion patterns (p
      = 0.001). The multiparametric approach decreased the false-positive value of real
      time elastography alone from 34.9% to 10.3% and improved the positive predictive
      value of cancer detection from 65.1% to 89.7%. CONCLUSIONS: Perfusion patterns of
      prostate cancer suspicious elastographic lesions are heterogeneous. However, the
      combined approach of real-time elastography and contrast enhanced ultrasound in
      this pilot study significantly decreased false-positive results and improved the
      positive predictive value of correctly identifying histopathological cancer.

PMID- 23164380
TI  - Editorial comment.

PMID- 23164381
TI  - "Trifecta" in partial nephrectomy.
AB  - PURPOSE: We introduce the concept of trifecta outcomes during
      robotic/laparoscopic partial nephrectomy, in which the 3 key outcomes of negative
      cancer margin, minimal renal functional decrease and no urological complications
      are simultaneously realized. We report serial trifecta outcomes in patients
      treated with robotic/laparoscopic partial nephrectomy for tumor in a 12-year
      period. MATERIALS AND METHODS: A total of 534 patients had complete data
      available and were retrospectively divided into 4 chronologic eras, including the
      discovery era--139 from September 1999 to December 2003, conventional hilar
      clamping era--213 from January 2004 to December 2006, early unclamping era--104
      from January 2007 to November 2008 and anatomical zero ischemia era--78 from
      March 2010 to October 2011. Renal functional decrease was defined as a greater
      than 10% reduction in the actual vs volume predicted postoperative estimated
      glomerular filtration rate. RESULTS: Across the 4 eras tumors trended toward
      larger size (2.9, 2.8, 3.1 and 3.3 cm, p = 0.08) and yet the estimated percent of
      kidney preserved was similar (89%, 90%, 90% and 88%, respectively, p = 0.3).
      Recent eras had increasingly complex tumors that were more often 4 cm or greater
      (p = 0.03), centrally located (p <0.009) or hilar (p <0.0001). Nevertheless, with
      significant technical refinement warm ischemia time decreased serially (36, 32,
      15 and 0 minutes, respectively, p <0.0001). Renal functional outcomes were
      superior in recent eras with fewer patients experiencing a decrease (p <0.0001).
      Uniquely, actual estimated glomerular filtration rate outcomes exceeded volume
      predicted estimated glomerular filtration rate outcomes only in the zero ischemia
      cohort in regard to other eras (-9.5%, -11%, -0.9% and 4.2%, respectively, p
      <0.001). Positive cancer margins were uniformly low at less than 1%. Urological
      complications trended lower in recent eras (p = 0.01). Trifecta outcomes occurred
      more commonly in recent eras (45%, 44%, 62% and 68%, respectively, p = 0.0002).
      CONCLUSIONS: Trifecta should be a routine goal during partial nephrectomy.
      Despite increasing tumor complexity, trifecta outcomes of robotic/laparoscopic
      partial nephrectomy improved significantly in the last decade.

PMID- 23164382
TI  - Certificate of need programs, intensity modulated radiation therapy use and the
      cost of prostate cancer care.
AB  - PURPOSE: Certificate of need programs are a primary mechanism to regulate the use
      and cost of health care services at the state level. The effect of certificate of
      need programs on the use of intensity modulated radiation therapy and the
      increasing costs of prostate cancer care is unknown. We compared the use of
      intensity modulated radiation therapy and change in prostate cancer health care
      costs in regions with vs without active certificate of need programs. MATERIALS
      AND METHODS: This population based, observational study using SEER (Surveillance,
      Epidemiology, and End Results)-Medicare linked data from 2002 through 2009 was
      comprised of 13,814 men treated for prostate cancer in 3 regions with active
      certificate of need programs (CON Yes) vs 44,541 men treated for prostate cancer
      in 9 regions without active certificate of need programs (CON No). We assessed
      intensity modulated radiation therapy use relative to other prostate cancer
      definitive therapies and overall prostate cancer health care costs with respect
      to certificate of need status. RESULTS: In propensity score adjusted analyses,
      intensity modulated radiation therapy use increased from 2.3% to 46.4% of
      prostate cancer definitive therapies in CON Yes regions vs 11.3% to 41.7% in CON
      No regions from 2002 to 2009. Furthermore, we observed greater intensity
      modulated radiation therapy use with time in CON Yes vs No regions (p <0.001).
      Annual cost growth did not differ between CON Yes vs No regions (p = 0.396).
      CONCLUSIONS: Certificate of need programs were not effective in limiting
      intensity modulated radiation therapy use or attenuating prostate cancer health
      care costs. There remains an unmet need to control the rapid adoption of new,
      more expensive therapies for prostate cancer that have limited cost and
      comparative effectiveness data.

PMID- 23164383
TI  - Pathological concordance and surgical outcomes of sporadic synchronous unilateral
      multifocal renal masses treated with partial nephrectomy.
AB  - PURPOSE: Patients with unilateral synchronous multifocal renal masses represent a
      unique population with renal cell carcinoma. While pathological concordance rates
      have been studied for bilateral cases, limited data exist on unilateral
      multifocal disease. We characterized pathological concordance rates in this
      population and evaluated the outcomes of nephron preservation. MATERIALS AND
      METHODS: Patients who underwent surgery from 2000 to 2012 for unilateral
      synchronous multifocal renal masses were identified from a prospectively
      maintained database. Demographic, surgical and pathological outcomes of this
      cohort were analyzed. Malignant concordance rates were defined as agreement of
      all malignant tumor types in a single renal unit. Histological concordance was
      defined as agreement of all resected mass histologies, eg all clear cell
      carcinomas. Nuclear grade was considered concordant if all tumors excised were
      low (Fuhrman 1 or 2, type 1) or high (Fuhrman 3 or 4, type 2) grade. RESULTS:
      Using our institutional database of 2,569 patients with renal tumors we
      identified 97 with unilateral synchronous multifocal renal masses. Malignant and
      benign concordance rates were 77.2% and 48.6%, and histological and grade
      concordance rates were 58.8% and 51.5%, respectively. In this cohort we
      identified 76 patients (76.3% male) with a median age of 62.5 years who had a
      total of 241 unilateral synchronous multifocal renal masses and underwent nephron
      sparing surgery. Median mass size was 2.0 cm (IQR 1.1-3.1), there was a median of
      3 tumors per patient and median followup was 24 months (IQR 13-40). Identified
      renal cell carcinoma histologies included clear cell in 49.4% of cases, papillary
      in 33.5%, mixed in 4.5% and chromophobe in 2.8%. CONCLUSIONS: In what is to our
      knowledge the largest published report of unilateral synchronous multifocal renal
      masses we document low pathological concordance rates. As such, percutaneous
      biopsy of a single renal mass in these patients may not help inform treatment
      decisions. Nephron sparing surgery may be performed with acceptable oncological
      and functional results in patients with unilateral synchronous multifocal renal
      masses.

PMID- 23164384
TI  - Is a sexual dysfunction domain important for quality of life in men with
      urological chronic pelvic pain syndrome? Signs "UPOINT" to yes.
AB  - PURPOSE: Clinical phenotyping to guide treatment for urological chronic pelvic
      pain syndrome is a promising strategy. The UPOINT (urinary, psychosocial, organ
      specific, infection, neurological/systemic and tenderness of the pelvic floor)
      phenotyping system evaluates men and women on 6 domains. However, this study
      focused on men only. Due to the high prevalence of sexual dysfunction in men with
      urological chronic pelvic pain syndrome, debate exists about the usefulness of
      adding an (S) (sexual dysfunction) domain to UPOINT. We examined the usefulness
      in terms of quality of life and delineated urological chronic pelvic pain
      syndrome subcategories using UPOINT(S) domains. MATERIALS AND METHODS: We
      assessed 162 men using UPOINT criteria and after adding the sexual dysfunction
      domain. Using multiple regression analysis UPOINT(S) criteria were then compared
      to quality of life, as measured by the SF-36(r) health outcome survey and Chronic
      Prostatitis Symptoms Index. Sample subgroups were assessed using k-means cluster
      analysis. RESULTS: The total number of UPOINT(S) domains correlated with SF-36
      and Chronic Prostatitis Symptoms Index scores. Using regression analysis the 2
      significant predictors of SF-36 scores were the psychosocial and sexual domains.
      Men with sexual dysfunction had significantly worse quality of life than men
      without the condition. In addition, 6 potentially clinically meaningful subgroups
      were identified using cluster analysis. Sexual dysfunction was differentially
      present in these groups. CONCLUSIONS: Adding a sexual dysfunction domain to
      UPOINT may help improve quality of life in men treated for urological chronic
      pelvic pain syndrome.

PMID- 23164385
TI  - [11C]choline positron emission tomography/computerized tomography for early
      detection of prostate cancer recurrence in patients with low increasing prostate
      specific antigen.
AB  - PURPOSE: The effectiveness of salvage therapy in prostate cancer is greater for
      low prostate specific antigen values. Therefore, early detection of tumor
      recurrence is warranted. [(11)C]choline positron emission tomography/computerized
      tomography has the potential of early restaging of prostate cancer with low
      prostate specific antigen, but the selection of patients at high risk for
      positive [(11)C]choline positron emission tomography/computerized tomography is
      desirable to optimize salvage therapy. MATERIALS AND METHODS: This retrospective
      study included 75 patients with prostate cancer with an increasing prostate
      specific antigen less than 1.5 ng/ml after radical prostatectomy who never
      received antiandrogen deprivation therapy or salvage radiotherapy who underwent
      [(11)C]choline positron emission tomography/computerized tomography for the
      restaging of disease. Binary logistic regression was used to assess predictive
      factors of positive [(11)C]choline positron emission tomography/computerized
      tomography. Included variables were trigger prostate specific antigen, prostate
      specific antigen doubling time, age, pathological stage and Gleason score.
      RESULTS: Median prostate specific antigen was 0.61 ng/ml. [(11)C]choline positron
      emission tomography/computerized tomography was positive in 16 of 75 patients
      (21%). On univariate analysis prostate specific antigen doubling time less than 6
      months was the only factor significantly associated with an increased risk of
      positive [(11)C]choline positron emission tomography/computerized tomography (OR
      7.77, 95% CI 2.34-25.80, p = 0.001). In patients with prostate specific antigen
      doubling time less than 6 months, the positive detection rate of [(11)C]choline
      positron emission tomography/computerized tomography increased to 50%.
      CONCLUSIONS: In patients with prostate cancer with biochemical failure after
      radical prostatectomy and prostate specific antigen less than 1.5 ng/ml, prostate
      specific antigen doubling time less than 6 months predicts positive
      [(11)C]choline positron emission tomography/computerized tomography. In these
      patients [(11)C]choline positron emission tomography/computerized tomography may
      reduce by 50% the number in whom salvage therapy is initiated empirically without
      knowing the disease location.

PMID- 23164386
TI  - The prevalence and overlap of interstitial cystitis/bladder pain syndrome and
      chronic prostatitis/chronic pelvic pain syndrome in men: results of the RAND
      Interstitial Cystitis Epidemiology male study.
AB  - PURPOSE: As part of the RICE (RAND Interstitial Cystitis Epidemiology) study, we
      developed validated case definitions to identify interstitial cystitis/bladder
      pain syndrome in women and chronic prostatitis/chronic pelvic pain syndrome in
      men. Using population based screening methods, we applied these case definitions
      to determine the prevalence of these conditions in men. MATERIALS AND METHODS: A
      total of 6,072 households were contacted by telephone to screen for men who had
      symptoms of interstitial cystitis/bladder pain syndrome or chronic
      prostatitis/chronic pelvic pain syndrome. An initial 296 men screened positive,
      of whom 149 met the inclusionary criteria and completed the telephone interview.
      For interstitial cystitis/bladder pain syndrome 2 case definitions were applied
      (1 with high sensitivity and 1 with high specificity), while for chronic
      prostatitis/chronic pelvic pain syndrome a single case definition (with high
      sensitivity and specificity) was used. These case definitions were used to
      classify subjects into groups based on diagnosis. RESULTS: The interstitial
      cystitis/bladder pain syndrome weighted prevalence estimates for the high
      sensitivity and high specificity definitions were 4.2% (3.1-5.3) and 1.9% (1.1
      2.7), respectively. The chronic prostatitis/chronic pelvic pain syndrome weighted
      prevalence estimate was 1.8% (0.9-2.7). These values equate to 1,986,972 (95% CI
      966,042-2,996,924) men with chronic prostatitis/chronic pelvic pain syndrome and
      2,107,727 (95% CI 1,240,485-2,974,969) men with the high specificity definition
      of interstitial cystitis/bladder pain syndrome in the United States. The overlap
      between men who met the high specificity interstitial cystitis/bladder pain
      syndrome case definition or the chronic prostatitis/chronic pelvic pain syndrome
      case definition was 17%. CONCLUSIONS: Symptoms of interstitial cystitis/bladder
      pain syndrome and chronic prostatitis/chronic pelvic pain syndrome are widespread
      among men in the United States. The prevalence of interstitial cystitis/bladder
      pain syndrome symptoms in men approaches that in women, suggesting that this
      condition may be underdiagnosed in the male population.

PMID- 23164387
TI  - Adolescent obesity and paternal country of origin predict renal cell carcinoma: a
      cohort study of 1.1 million 16 to 19-year-old males.
AB  - PURPOSE: The incidence of renal cell carcinoma has increased in recent decades,
      particularly among middle-aged adults. Early precursors of renal cancer remain
      unclear. We evaluated the association of body mass index and height determined in
      late adolescence, and paternal or grandpaternal country of origin with the risk
      of renal cell carcinoma. MATERIALS AND METHODS: Health related data on 1,110,835
      males at ages 16 to 19 years who were examined for fitness for military service
      between 1967 and 2005 were linked to the Israel National Cancer Registry in this
      nationwide, population based cohort study. We used Cox proportional hazards
      modeling to estimate the HR of renal cell carcinoma associated with birth year,
      body mass index, height, father country of origin and socioeconomic indicators.
      RESULTS: During 19,576,635 person-years of followup renal cancer developed in 274
      examinees. Substantial excess risk was conferred by a body mass index of greater
      than 27.5 kg/m(2) compared to less than 22.5 kg/m(2) (HR 2.43, 95% CI 1.54-3.83,
      p <0.0001). Asian or African origin was protective compared to European origin
      (African origin HR 0.67, 95% CI 0.49-0.92). CONCLUSIONS: Overweight in late
      adolescence is a substantial risk factor for renal cell carcinoma. European
      origin is independently associated with excess risk and it persists among Israeli
      born males. Preventing childhood obesity may be a promising target for decreasing
      the burden of renal cancer.

PMID- 23164388
TI  - Certificate of need legislation and the dissemination of robotic surgery for
      prostate cancer.
AB  - PURPOSE: The uncertainty about the incremental benefit of robotic prostatectomy
      and its higher associated costs makes it an ideal target for state based
      certificate of need laws, which have been enacted in several states. We studied
      the relationship between certificate of need laws and market level adoption of
      robotic prostatectomy. MATERIALS AND METHODS: We used SEER (Surveillance,
      Epidemiology, and End Results)-Medicare data from 2003 through 2007 to identify
      men 66 years old or older treated with prostatectomy for prostate cancer. Using
      data from the American Health Planning Association, we categorized Health Service
      Areas according to the stringency of certificate of need regulations (ie low vs
      high stringency) presiding over that market. We assessed our outcomes
      (probability of adopting robotic prostatectomy and propensity for robotic
      prostatectomy use in adopting Health Service Areas) using Cox proportional
      hazards and Poisson regression models, respectively. RESULTS: Compared to low
      stringency markets, high stringency markets were more racially diverse (54% vs
      15% nonwhite, p <0.01), and had similar population densities (886 vs 861 people
      per square mile, p = 0.97) and median incomes ($42,344 vs $39,770, p = 0.56). In
      general, both market types had an increase in the adoption and utilization of
      robotic prostatectomy. However, the probability of robotic prostatectomy adoption
      (p = 0.22) did not differ based on a market's certificate of need stringency and
      use was lower in high stringency markets (p <0.01). CONCLUSIONS: State based
      certificate of need regulations were ineffective in constraining robotic surgery
      adoption. Despite decreased use in high stringency markets, similar adoption
      rates suggest that other factors impact the diffusion of robotic prostatectomy.

PMID- 23164389
TI  - Validation of new AJCC exclusion criteria for subepithelial prostatic stromal
      invasion from pT4a bladder urothelial carcinoma.
AB  - PURPOSE: In 2010 the AJCC (American Joint Committee on Cancer) excluded
      urothelial carcinoma with subepithelial prostatic stromal invasion from the pT4a
      bladder cancer staging class, which is otherwise defined by direct prostatic
      invasion transmurally from the bladder. We determined if the new guidelines were
      reflective of differences in survival between subepithelial prostatic stromal
      invasion and transmural pT4a disease. MATERIALS AND METHODS: A retrospective,
      multi-institutional cohort of cystectomy cases with subepithelial prostatic
      stromal invasion from the University of Chicago and Cleveland Clinic were
      compared to a cohort with transmural pT4a disease. All pathological specimens
      were rereviewed at the respective institutions. Patients were excluded from the
      final cohort if variant bladder cancer histology, pT3 bladder disease or
      extraprostatic extension of urothelial carcinoma were identified. The primary end
      points were cancer specific and overall survival. RESULTS: Our study sample
      consisted of 48 patients with subepithelial prostatic stromal invasion and 49
      patients with transmural pT4a disease. Median followup was 12.8 months (IQR 4.9
      to 31.4). Patients with subepithelial prostatic stromal invasion had lower rates
      of lymph node involvement than those with transmural pT4a disease (14.6% vs
      61.2%, p <0.001) and lower rates of positive surgical margins (18.7% vs 61.2%, p
      <0.001). Rates of perioperative chemotherapy were similar in both groups. When
      comparing subepithelial prostatic stromal invasion and transmural pT4a groups,
      overall survival was 64.0 vs 9.8 months and median cancer specific survival was
      not achieved vs 16.5 months, respectively (p <0.001). CONCLUSIONS: Subepithelial
      prostatic stromal invasion from urothelial carcinoma has more favorable outcomes
      compared to transmural pT4a disease. Our results support the exclusion of
      subepithelial prostatic stromal invasion from the pT4a bladder urothelial
      carcinoma staging class.

PMID- 23164390
TI  - Nephrostomy tube related pyelonephritis in patients with cancer: epidemiology,
      infection rate and risk factors.
AB  - PURPOSE: Nephrostomy tube placement is often necessary to avert acute renal
      failure in patients with cancer with obstructive uropathy or in patients with
      ureteral leak. However, there have been limited published studies on the rate and
      risk of nephrostomy tube related pyelonephritis in patients with cancer.
      Therefore, in this study we determined rates of nephrostomy tube related
      pyelonephritis and predisposing risk factors in patients with cancer. MATERIALS
      AND METHODS: We retrospectively reviewed patients who underwent nephrostomy tube
      placement between September 1, 2009 and September 16, 2010 at MD Anderson Cancer
      Center. Patients were followed for 90 days. The primary outcome assessed was the
      development of nephrostomy tube related pyelonephritis and the secondary outcome
      was the development of asymptomatic bacteriuria. We also determined risk factors
      associated with pyelonephritis. RESULTS: Of the 200 patients analyzed 38 (19%)
      had pyelonephritis and 15 (7.5%) had asymptomatic bacteriuria. Of the nephrostomy
      tube related infections 34 cases (89%) were with the primary nephrostomy tube.
      Subsequently 4 of the patients who underwent nephrostomy tube exchange had an
      episode of pyelonephritis. Pyelonephritis developed within the first month in 19
      (10%) patients. Prior urinary tract infection and neutropenia were found to be
      significant risk factors for pyelonephritis (p = 0.047 and 0.03, respectively).
      CONCLUSIONS: The placement of nephrostomy tubes in patients with cancer is
      associated with a significant rate of pyelonephritis. Neutropenia and history of
      urinary tract infection were significant risk factors for pyelonephritis. This
      finding warrants further investigation into preventive strategies to reduce the
      infection rate.

PMID- 23164392
TI  - Clinically significant prostate cancer is rarely missed by ablative procedures of
      the prostate in men with prostate specific antigen less than 4 ng/ml.
AB  - PURPOSE: Laser vaporization of the prostate is widely used to treat lower urinary
      tract symptoms. It may decrease the hospital cost and morbidity associated with
      transurethral resection of the prostate. However, prostate cancer may go
      undetected because tissue is not taken at laser vaporization. To our knowledge
      the rate of clinically significant prostate cancer missed by laser vaporization
      has not been assessed to date. We determined the rate of clinically significant
      prostate cancer detected by transurethral resection of the prostate compared to
      the estimated number of cancers missed by laser vaporization. MATERIALS AND
      METHODS: A total of 74,505 men diagnosed with stage T1 prostate cancer between
      2004 and 2006 were identified from the SEER (Surveillance, Epidemiology and End
      Results) program in the United States. The total number of laser vaporizations
      and transurethral resections were calculated based on Medicare claims for the
      same period. Clinically significant cancer was defined as that with a Gleason
      score of 7 or greater in men 40 to 75 years old. RESULTS: If prostate specific
      antigen screening were used uniformly (excluding men with prostate specific
      antigen greater than 4 ng/ml), only 1 of 382 transurethral resections of the
      prostate would identify clinically significant prostate cancer for a total of 390
      in the American population in 3 years. Based on Medicare reported laser
      vaporization use a total of only 163 clinically significant cancers would be
      missed in more than 60,000 procedures. CONCLUSIONS: The incidence of T1a and T1b
      prostate cancer remains low and few patients have clinically significant prostate
      cancer. When prostate specific antigen screening is used, the number of
      clinically significant tumors missed by ablative procedures is low (average of
      0.26% of all procedures) and can be identified by prostate specific antigen
      screening.

PMID- 23164391
TI  - Hospitalization trends after prostate and bladder surgery: implications of
      potential payment reforms.
AB  - PURPOSE: Hospital stays have decreased for patients undergoing surgery for
      urological cancer. However, there are concerns that patients are being discharged
      from the hospital prematurely. We examined associations between hospital stay and
      short-term outcomes for a low risk procedure (prostatectomy) and high risk
      procedure (cystectomy). MATERIALS AND METHODS: We used SEER (Surveillance,
      Epidemiology and End Results)-Medicare data from 1992 through 2005 to identify
      46,781 prostatectomy and 9,035 cystectomy cases. We assessed our main outcome
      (adjusted likelihood of hospital readmission within 30 days) using a logistic
      regression model. Secondary outcomes included mortality rates and discharge
      disposition. RESULTS: In comparing patients from 1992 to 1993, to 2004 to 2005,
      hospital stay decreased approximately 3 days for both surgeries (relative
      decrease of more than 50% for prostatectomy and 21% for cystectomy). Hospital
      readmission rates were 4.5% and 25.2% for prostatectomy and cystectomy,
      respectively, and remained stable with time. Skilled nursing/intermediate care
      use was stable for patients who underwent prostatectomy (approximately 1%), but
      increased from 8.2% (95% CI 5.4-11.4) to 18.9% (95% CI 16.8-21.3) for those
      treated with cystectomy. Use of home care increased from 8.1% (95% CI 7.3-9.0) to
      11.1% (95% CI 10.1-12.1) and from 34.2% (95% CI 29.7-38.7) to 47.5% (95% CI 44.5
      50.1) for prostatectomy and cystectomy cases, respectively. CONCLUSIONS:
      Reductions in hospital stay were more dramatic for patients who underwent
      prostatectomy and were associated with stable short-term outcomes. Conversely,
      smaller reductions in hospitalization for patients undergoing cystectomy were met
      with substantial increases in the use of post-acute care. Going forward, close
      surveillance of how imminent policy reforms affect patterns and quality of care
      will be necessary.

PMID- 23164393
TI  - Effect of age on the clinical presentation of incident symptomatic urolithiasis
      in the general population.
AB  - PURPOSE: We characterized variation in the clinical presentation between older
      and younger first time symptomatic stone formers in the general population.
      MATERIALS AND METHODS: We studied a random sample of Olmsted County, Minnesota
      residents with their first diagnostic code for urolithiasis between 1984 and
      2003. Chart validated symptomatic stone formers had a confirmed stone by imaging
      or stone passage. Clinical presentation characteristics were compared between age
      groups. RESULTS: Among the 3,473 charts reviewed there were 1,590 validated
      incident symptomatic stone formers (mean age 43 years, range 18 to 96). Older
      individuals were more likely to present with atypical or no pain, fever,
      diarrhea, pyuria, urinary tract infections and bacteremia (p <0.001). Stone size
      and location did not differ by patient age. Calcium phosphate stone disease was
      associated with younger age, while uric acid stone and atypical stone composition
      was associated with older age (p <0.001). Older individuals were less likely to
      pass the stone spontaneously and were more likely to require surgical
      intervention (p <0.001). Surgical intervention was required in 516 (32.5%)
      individuals. Younger individuals were more likely to undergo ureteroscopy while
      older individuals were more likely to undergo shock wave lithotripsy, temporizing
      stent placement and percutaneous nephrolithotomy. CONCLUSIONS: The detection of
      stone disease in older individuals can be challenging due to atypical pain or
      absence of pain, as well as the presence of other comorbid conditions such as
      urinary tract infections and diarrhea. A higher index of suspicion for
      urolithiasis may be needed in the elderly for a more timely diagnosis and
      intervention to prevent morbidity.

PMID- 23164394
TI  - Occupational exposure to herbs containing aristolochic acids increases the risk
      of urothelial carcinoma in Chinese herbalists.
AB  - PURPOSE: Aristolochic acid can cause urothelial carcinoma. Herbal remedies
      containing aristolochic acids were previously categorized as proven group 1 human
      carcinogens by the WHO cancer agency, the International Agency for Research on
      Cancer. However, the health effect on workers exposed to aristolochic acid is
      unclear. Fangchi, a representative herb containing aristolochic acid, is commonly
      used in the Chinese herbal medicine industry. We determined whether workers
      exposed to fangchi are at increased risk for urothelial carcinoma. MATERIALS AND
      METHODS: We designed a case-control study based in a national representative
      cohort of Chinese herbalists. This study analyzed 6,564 Chinese herbalists
      employed between 1985 and 1998. All incident cases of urothelial carcinoma that
      occurred between 1988 and 2001 were defined as the case group. Controls were
      selected from the baseline cohort in a randomized manner. A total of 24 cases and
      140 controls were included in analysis. Information about fangchi exposure was
      obtained in a questionnaire survey administered in 2002. RESULTS: Processing,
      selling or dispensing herbs containing fangchi significantly increased the risk
      of urothelial carcinoma (HR 2.4, 95% CI 1.1-5.3, p = 0.03). This relationship was
      independent of cigarette smoking or potential arsenic exposure from drinking
      water from deep wells. CONCLUSIONS: Exposure to the Chinese herbal drug fangchi
      increases the risk of urothelial carcinoma in herbalists. Appropriate medical
      monitoring is warranted for workers who have similar exposure.

PMID- 23164395
TI  - Food ingredients and supplements: is this the future?

PMID- 23164396
TI  - History, prejudice, and the study of social inequities.
AB  - Integrating a historical perspective into studies of prejudicial attitudes
      facilitates the interpretation of paradoxical findings of the kind cited in the
      target article. History also encourages research to move beyond the study of
      prejudice and to consider institutional and structural forces that maintain
      social inequities. Multilevel approaches can study these factors in both field
      and laboratory studies.

PMID- 23164397
TI  - Expression patterns of activin, inhibin and follistatin variants in the adult
      male mouse reproductive tract suggest important roles in the epididymis and vas
      deferens.
AB  - Activin A and its inhibitors follistatin and inhibin play key roles in
      development and function of the male reproductive tract. Quantitative (q)
      polymerase chain reaction (PCR) was used to evaluate the expression of Inhba (the
      gene encoding activin A subunits), Inha and Inhbb (genes encoding the inhibin B
      subunits), as well as the genes for follistatin (Fst) and follistatin-like 3
      (Fstl3) and the activin receptor subunits, in the male mouse reproductive tract.
      A qPCR assay that discriminated between the two follistatin variants of Fst288
      (tissue-bound form) and Fst315 (circulating) was established. Activin A protein
      was measured by ELISA, whereas the inhibin alpha-subunit and total follistatin
      proteins were measured by radioimmunoassay (RIA). A screen of 22 tissues
      demonstrated tissue-specific regulation of the follistatin variants, with Fst288
      highly expressed in the vas deferens and Fst315 most highly expressed in the
      skin. The expression of Fst288 and Fst315 and follistatin protein levels
      increased progressively from the testis through to the distal vas deferens. Inhba
      and the activin receptors were highly expressed in the epididymis, but activin A
      protein was elevated in both the epididymis and vas deferens. Inhibin alpha
      subunit mRNA and protein and Inhbb expression were highest in the testis. These
      results indicate a role for activin A within the epididymis, but also that
      activin A bioactivity may be increasingly inhibited by follistatin distally along
      the male reproductive tract.

PMID- 23164398
TI  - Litter production and litter elemental composition in two rehabilitated Kandelia
      obovata mangrove forests in Jiulongjiang Estuary, China.
AB  - Spatial and seasonal variations in litter production and C, N, and P
      concentrations were compared between the 24 and 48 year old Kandelia obovata
      mangrove forests in the Jiulongjiang estuary, China. The 24 yr forest had
      significantly higher production of total, leaf and branch litter, but lower
      flower and fruit litter than the 48 yr forest. Total, leaf and branch litter
      production were significantly positively correlated to monthly temperature and
      rainfall. Spatial patterns of litter production among the inner, mid and outer
      zones in the same forest were similar to those of tree heights. C, N and P
      concentrations of leaf litter showed significant seasonality but varied little
      among these three forest zones. C/N and N/P ratios of leaf litter were
      significantly lower for the 24 yr forest than those for the 48 yr forest. During
      the entire sampling year, total litter of the 24 and 48 yr forests contained
      590.31 and 437.31 g C m(-2) yr(-1), 8.46 and 5.47 g N m(-2) yr(-1), 1.92 and 1.16
      g P m(-2) yr(-1), respectively.

PMID- 23164399
TI  - The stigma surrounding mental illness persists.

PMID- 23164400
TI  - Clinging to any bit of joy: urban, ethnically diverse, impoverished women's
      descriptions of anxiety and depression.
AB  - Depression and anxiety are mental health issues that disproportionately affect
      women. This study sought to capture perceptions of anxiety and depression in 3
      urban, ethnically diverse, underserved, and impoverished neighborhoods. Using
      community-based participatory research, in the context of long-term partnerships
      between a department of nursing and these neighborhoods, the researchers
      recruited 61 women aged 18 to 69 years. Data were collected via 6 homogeneous
      focus groups composed of Black, Hispanic, and White women, respectively. The
      women identified themes pertaining to the manifestations and effects of anxiety
      and depression as well as unique coping strategies.

PMID- 23164401
TI  - The INFORM project: a service user-led research endeavor.
AB  - Effective engagement with people who experience mental health care services, as
      research participants and as research leads, is presented. A group of volunteer
      mental health survivors, called INFORM, worked for 6 years to develop and
      complete a research project, exploring service user experience of a home
      treatment and crisis resolution service. Within the article, discussion is given
      to the significance of service continuity, alongside personal accounts of the
      impact and consequences of health care staff's interpersonal interactions. Two
      contrasting messages arise from this study: first, the articulation of what
      services users want from services, and how that relates to what they actually
      receive, continues to be a necessary debate and issue for consideration at a time
      of considerable health care reform. The second message is that such articulation,
      although necessary, is not sufficient in itself to ensure that services are
      responsive to service user needs and preferences. Findings from the evaluation
      are consistent with other service user-led research. However, what is also
      evident is that more work is required in enabling health care consumers to
      provide feedback that can then be used to inform practice and service delivery
      improvement.

PMID- 23164402
TI  - Satisfaction with and benefits of a psych-social club: development of a mixed
      method evaluation instrument.
AB  - There are no instruments for validation or evaluation of a member's satisfaction
      of and benefits with psych-social clubs. This article reports on the development
      and testing of the mixed-method instrument entitled Benefits and Satisfaction
      Tool for Members of a Psych-social Club (B&ST-MPC), which evolved from findings
      of a qualitative research study. The alpha reliability coefficient was .92. The
      Kaiser-Meyer-Olkin Test yielded a value of .812. The items loaded on 3 factors.
      Utilization of B&ST-MPC supports development of services for rural communities
      through feedback from consumers. Further testing of the B&ST-MPC in settings with
      diverse populations is recommended.

PMID- 23164403
TI  - Attitudes and beliefs regarding depression, HIV/AIDS, and HIV risk-related sexual
      behaviors among clinically depressed African American adolescent females.
AB  - Individuals' attitudes and beliefs toward behaviors are key indicators of
      behavioral performance. The purposes of this study were to elucidate attitudes
      and beliefs about depression, HIV/AIDS, and HIV risk-related sexual behaviors
      among clinically depressed African American adolescent females and to develop an
      understanding of their context for HIV risk. For this descriptive qualitative
      inquiry, semistructured interviews and surveys were employed (N = 24). The
      narratives reveal that behavioral sequelae of depression (i.e., loneliness) can
      produce risk for HIV. These findings may guide psychiatric nurse educators,
      scientists, and practitioners to modify HIV risk among clinically depressed
      African American adolescent females.

PMID- 23164404
TI  - Chronic stress, somatic and depressive symptoms following mild to moderate
      traumatic brain injury.
AB  - Despite advances in research on symptoms, stress, and depression after traumatic
      brain injury, there has been limited focus on the collective relationships
      between neurocognitive performance, chronic stress, and somatic and depressive
      symptoms. Guided by our adaptation of the allostatic load theory, we examined
      relationships between chronic stress, somatic and depressive symptoms, and
      cognitive performance using the Immediate Postconcussion Assessment and Cognitive
      Testing cognitive battery. Only somatic symptoms and chronic stress explained
      variation in depressive symptoms (R(2) = .71, P < .0001), not neurocognitive
      performance, preinjury, or injury-specific variables. Our findings suggest that
      increased chronic stress and somatic symptoms can contribute significantly to
      depressive symptoms after mild to moderate traumatic brain injury.

PMID- 23164405
TI  - Assessing aggressive behavior in forensic psychiatric patients: validity and
      clinical utility of combining two instruments.
AB  - OBJECTIVES: Accurate observation of aggressive behavior among forensic
      psychiatric patients requires valid instruments. This study examines the validity
      and clinical utility of combining the social dysfunction and aggression scale
      (SDAS) and staff observation aggression scale revised (SOAS-R). METHODS: Nurses
      weekly obtained SDAS scores of 127 patients, resulting in 6.124 assessments.
      Aggressive incidents were documented by the SOAS-R. Internal consistency,
      subscale structure, interobserver reliability of the SDAS, and convergent
      validity with SOAS-R were analyzed. CONCLUSION: A three-factor solution was
      found. Interobserver reliability was moderate, and good convergent validity was
      found. The SDAS, in conjunction with the SOAS-R, monitors changes in
      aggressiveness and may contribute to the prevention of aggressive behavior.

PMID- 23164406
TI  - Ethical problems experienced by psychiatric nurses in Korea.
AB  - This study aimed to explore the ethical problems experienced by psychiatric
      nurses in a clinical setting. Data were collected using semistructured interviews
      with a purposive sample of 12 female psychiatric nurses from 3 psychiatric
      facilities in Korea. A thematic content analysis was used to identify ethical
      problems. The study illustrated 5 categories of ethical problems: moral
      unpreparedness and blindness, moral numbness, moral complacency, moral conflict,
      and moral stress. This study provides a theoretical basis of psychiatric ethical
      problems for developing ethical guidelines that will enable psychiatric nurses to
      make decisions reasonably and behave ethically in their workplace.

PMID- 23164407
TI  - Risks, benefits and survival strategies-views from female sex workers in
      Savannakhet, Laos.
AB  - BACKGROUND: Female sex workers (FSWs) are vulnerable to sexually transmitted
      infections (STIs) and encounter socio-economic and health problems, including
      STIs/HIV, unintended pregnancy and complications from unsafe abortion, stigma,
      violence, and drug addiction. Reducing risks associated with sex work requires an
      understanding of the social and cultural context in which sex workers live and
      work. This study aimed to explore the working environment and perceived risks
      among FSWs in Savannakhet province in Laos. METHODS: Five focus group discussions
      (FGDs) and seven interviews were conducted with FSWs in Kaysone Phomvihan
      district in Laos. Latent content analysis was used to analyze the transcribed
      text. RESULTS: The results revealed that the FSWs were aware of risks but they
      also talked about benefits related to their work. The risks were grouped into six
      categories: STIs/HIV, unintended pregnancy, stigma, violence, being cheated, and
      social and economic insecurity. The reported benefits were financial security,
      fulfilling social obligations, and sexual pleasure. The FSWs reported using a
      number of strategies to reduce risks and increase benefits. CONCLUSIONS: The
      desire to be self-sufficient and earn as much money as possible put the FSWs in
      disadvantaged and vulnerable situations. Fear of financial insecurity,
      obligations to support one's family and the need to secure the future influenced
      FSWs' decisions to have safe or unsafe sex. The FSWs were, however, not only
      victims. They also had some control over their lives and working environment,
      with most viewing their work as an easy and good way of earning money.

PMID- 23164408
TI  - New role for an old rule: N-end rule-mediated degradation of ethylene responsive
      factor proteins governs low oxygen response in plants(F).
AB  - The N-end rule pathway regulates protein degradation, which depends on exposed N
      terminal sequences in prokaryotes and eukaryotes. In plants, conserved and
      specific enzymes stimulate selective proteolysis. Although a number of
      developmental and growth phenotypes have been reported for mutants in the N-end
      rule, its function has remained unrelated to specific physiological pathways. The
      first report of the direct involvement of the N-end rule in stress responses
      focused on hypoxic signaling and how the oxygen-dependent oxidation of cystein
      promotes the N-end rule-mediated degradation of ethylene responsive factor (ERF)
      VII proteins, the master regulators of anaerobic responses. It has been suggested
      that plants have evolved specific mechanisms to tune ERF-VII availability in the
      nucleus. In this review, we speculate that ERF-VII proteins are reversibly
      protected from degradation via membrane sequestration. The oxidative response in
      plants subjected to anoxic conditions suggests that reactive oxygen and nitrogen
      species (reactive oxygen species and reactive nitrogen species) may interact or
      interfere with the N-end rule pathway-mediated response to hypoxia.

PMID- 23164409
TI  - Accelerated pentose utilization by Corynebacterium glutamicum for accelerated
      production of lysine, glutamate, ornithine and putrescine.
AB  - Because of their abundance in hemicellulosic wastes arabinose and xylose are an
      interesting source of carbon for biotechnological production processes. Previous
      studies have engineered several Corynebacterium glutamicum strains for the
      utilization of arabinose and xylose, however, with inefficient xylose utilization
      capabilities. To improve xylose utilization, different xylose isomerase genes
      were tested in C. glutamicum. The gene originating from Xanthomonas campestris
      was shown to have the highest effect, resulting in growth rates of 0.14 h(-1),
      followed by genes from Bacillus subtilis, Mycobacterium smegmatis and Escherichia
      coli. To further increase xylose utilization different xylulokinase genes were
      expressed combined with X. campestris xylose isomerase gene. All combinations
      further increased growth rates of the recombinant strains up to 0.20 h(-1) and
      moreover increased biomass yields. The gene combination of X. campestris xylose
      isomerase and C. glutamicum xylulokinase was the fastest growing on xylose and
      compared with the previously described strain solely expressing E. coli xylose
      isomerase gene delivered a doubled growth rate. Productivity of the amino acids
      glutamate, lysine and ornithine, as well as the diamine putrescine was increased
      as well as final titres except for lysine where titres remained unchanged. Also
      productivity in medium containing rice straw hydrolysate as carbon source was
      increased.

PMID- 23164410
TI  - Transcriptome database resource and gene expression atlas for the rose.
AB  - BACKGROUND: For centuries roses have been selected based on a number of traits.
      Little information exists on the genetic and molecular basis that contributes to
      these traits, mainly because information on expressed genes for this economically
      important ornamental plant is scarce. RESULTS: Here, we used a combination of
      Illumina and 454 sequencing technologies to generate information on Rosa sp.
      transcripts using RNA from various tissues and in response to biotic and abiotic
      stresses. A total of 80714 transcript clusters were identified and 76611 peptides
      have been predicted among which 20997 have been clustered into 13900 protein
      families. BLASTp hits in closely related Rosaceae species revealed that about
      half of the predicted peptides in the strawberry and peach genomes have orthologs
      in Rosa dataset. Digital expression was obtained using RNA samples from organs at
      different development stages and under different stress conditions. qPCR
      validated the digital expression data for a selection of 23 genes with high or
      low expression levels. Comparative gene expression analyses between the different
      tissues and organs allowed the identification of clusters that are highly
      enriched in given tissues or under particular conditions, demonstrating the
      usefulness of the digital gene expression analysis. A web interface ROSAseq was
      created that allows data interrogation by BLAST, subsequent analysis of DNA
      clusters and access to thorough transcript annotation including best BLAST
      matches on Fragaria vesca, Prunus persica and Arabidopsis. The rose peptides
      dataset was used to create the ROSAcyc resource pathway database that allows
      access to the putative genes and enzymatic pathways. CONCLUSIONS: The study
      provides useful information on Rosa expressed genes, with thorough annotation and
      an overview of expression patterns for transcripts with good accuracy.

PMID- 23164411
TI  - Improving myelin/oligodendrocyte-related dysfunction: a new mechanism of
      antipsychotics in the treatment of schizophrenia?
AB  - Schizophrenia is a severe psychiatric disorder with complex clinical
      manifestations and its aetiological factors remain unclear. During the past
      decade, the oligodendrocyte-related myelin dysfunction was proposed as a
      hypothesis for schizophrenia, supported initially by a series of neuroimaging
      studies and genetic evidence. Recently, the effects of antipsychotics on
      myelination and oligodendroglial lineage development and their underlying
      molecular mechanisms were evaluated. Data from those studies suggest that the
      antipsychotics-resulting improvement in myelin/oligodendrocyte-related
      dysfunction may contribute, at least in part, to their therapeutic effect on
      schizophrenia. Importantly, these findings may provide the basis for a new
      insight into the therapeutic strategy by targeting the oligodendroglia lineage
      cells against schizophrenia.

PMID- 23164412
TI  - Using antimicrobial adjuvant therapy in cancer treatment: a review.
AB  - Recent clinical and pre-clinical data demonstrate that adjuvant antimicrobial
      therapy is beneficial in cancer treatment. There could be several reasons for
      this effect, which include treating cancer associated bacteria and viruses,
      prophylaxis of post-chemotherapy infections due to immunosuppression, and
      antiproliferative effect of certain antimicrobials. Targeting cancer associated
      viruses and bacteria with antimicrobial agents is currently used for gastric,
      cervical, hematopoietic, liver and brain cancer. However this treatment is
      effective only in combination with conventional therapies. Antimicrobials can
      also have a direct antiproliferative and cytotoxic effect, and can cause
      apoptosis. Moreover, some antimicrobials are known to be helpful in overcoming
      side effects of drugs commonly used in cancer treatment. Chemotherapy related
      bacteremia and neutropenia can be overcome by the appropriately timed use of
      antimicrobials. This review summarizes the data on the effects of antivirals and
      antibiotics on cancer treatment and describes their mechanisms.

PMID- 23164413
TI  - Outcome of patent ductus arteriosus ligation in premature infants in the East of
      England: a prospective cohort study.
AB  - BACKGROUND: Surgical ligation of patent ductus arteriosus is considered when
      medical treatment fails or is contraindicated. This study aims to determine the
      mortality and morbidity of preterm neonates referred for patent ductus arteriosus
      ligation. METHODS: A prospective study was conducted in the East of England to
      follow the outcome of premature infants under 37 weeks' gestation undergoing
      patent ductus arteriosus ligation. A standardised proforma was used to collect
      information before and after the procedure. RESULTS: A total of 102 premature
      infants were recruited, and patent ductus arteriosus ligation was performed in
      92. Surgical complications occurred in 8.7% (8/92), which included pneumothorax
      (5/8), recurrent laryngeal nerve palsy (2/8), and chylothorax (1/8). Morbidity
      outcome data were not available for all infants. The incidence of chronic lung
      disease was 88% (88/99); intraventricular haemorrhage was 49% (49/100);
      necrotising enterocolitis 39% (39/99), and retinopathy of prematurity 42%
      (41/97). The overall mortality rate in our study was 7.8% (8/102). Mortality rate
      in infants who had patent ductus arteriosus ligation was 4.3% (4/92). The 30-day
      survival rate after ligation was 99% (91/92). Beyond 30 days post-ligation, three
      infants died from other causes that were not directly related to surgery.
      CONCLUSION: Patent ductus arteriosus ligation in premature infants is associated
      with low mortality and complication rates; however, there is a high incidence of
      neonatal morbidity. Surgical capacity for patent ductus arteriosus ligation needs
      to be carefully planned nationally as the duration of ''waiting time'' and
      transport to another surgical centre could adversely affect outcomes in this high
      risk population.

PMID- 23164414
TI  - Clinical and pathological analysis of hepatitis B virus-related membranous
      nephropathy and idiopathic membranous nephropathy.
AB  - OBJECTIVE: The Hepatitis B virus infection rate is high in the Chinese
      population. The implications of HBV infection are widely recognized, and
      membranous glomerulonephritis is the most common renal lesion associated with HBV
      infection. We compared the clinicopathologic features of 119 HBV-related
      membranous nephropathy (HBV-MN) and 143 idiopathic membranous nephropathy (IMN)
      patients to identify those factors that facilitate their discrimination. METHODS:
      Cohort analysis of demographic information, clinical manifestations, laboratory
      parameters, renal pathology and prognostic features of the two groups. RESULTS:
      Most HBV-MN patients were young or middle-aged; the onset age in the HBVMN group
      was younger than the IMN group (p < 0.05). A male predominance was found in both
      groups. And the two groups both presented with heavy proteinuria or nephrotic
      syndrome. In contrast to IMN patients, the HBV-MN group was presented with a high
      occurrence of microscopic hematuria (73.95 vs. 35.66%) and renal insufficiency
      (47.06 vs. 24.48%). Plasma complement C3 and C4 in HBV-MN patients were
      significantly lower than in IMN patients (p < 0.05). The hyperlipidemia was more
      severe in IMN patients (p < 0.05). The occurrences of segmental glomerular
      damage, mesangial cell proliferation and tubulointerstitial damage were more
      common in the HBV-MN group (p < 0.05). Immunofluorescence staining of polyclonal
      immunoglobulin and polytypic complement immunoglobulin were more frequent in the
      HBV-MN group. The followup data showed there were no statistic differences in the
      prognosis between HBV-MN and IMN. CONCLUSION: HBV-MN patients commonly showed
      nephrotic syndrome accompanied with renal and hepatic dysfunction which was
      different from IMN patients. The primary pathological feature of HBVMN was
      atypical membranous nephropathy, which is usually associated with the
      inflammatory changes in HBV infection. The renal survival rates did not differ
      between HBVMN patients and IMN patients.

PMID- 23164415
TI  - Acute kidney injury in the pregnant patient.
AB  - Acute kidney injury (AKI) is costly and is associated with increased mortality
      and morbidity. An understanding of the renal physiologic changes that occur
      during pregnancy is essential for proper evaluation, diagnosis, and management of
      AKI. As in the general population, AKI can occur from prerenal, intrinsic, and
      post-renal causes. Major causes of pre-renal azotemia include hyperemesis
      gravidarum and uterine hemorrhage in the setting of placental abruption.
      Intrinsic etiologies include infections from acute pyelonephritis and septic
      abortion, bilateral cortical necrosis, and acute tubular necrosis. Particular
      attention should be paid to specific conditions that lead to AKI during the
      second and third trimesters, such as preeclampsia, HELLP syndrome, acute fatty
      liver of pregnancy, and TTP-HUS. For each of these disorders, delivery of the
      fetus is the recommended therapeutic option, with additional therapies indicated
      for each specific disease entity. An understanding of the various etiologies of
      AKI in the pregnant patient is key to the appropriate clinical management,
      prevention of adverse maternal outcomes, and safe delivery of the fetus. In
      pregnant women with pre-existing kidney disease, the degree of renal dysfunction
      is the major determining factor of pregnancy outcomes, which may further be
      complicated by a prior history of hypertension.

PMID- 23164416
TI  - Development of Wernicke's encephalopathy during initiation of hemodialysis in an
      elderly non-alcoholic patient.
AB  - A 79-year-old man with chronic renal failure developed general fatigue and loss
      of appetite. He was diagnosed with endstage renal disease and was started on
      hemodialysis (HD). The symptoms improved immediately, but the mental status
      deteriorated gradually, reaching Glasgow Coma Scale (GCS) 5. Computed tomography
      showed no significant intracranial lesion, but magnetic resonance images showed
      symmetric high-intensity changes in the periaqueductal area, suggestive of
      Wernicke's encephalopathy (WE). He was immediately treated with intravenous
      infusion of thiamine. Five days later, the mental status level improved up to GCS
      14, and the above MRI findings disappeared. To our knowledge, this is the first
      report describing the clinical outcome of a non-alcoholic patient who developed
      WE during initiation of HD. WE should be suspected in patients who are on chronic
      HD as well as those on initiation of HD with unexplained neurological
      abnormalities.

PMID- 23164417
TI  - Bartter syndrome type III and congenital anomalies of the kidney and urinary
      tract: an antenatal presentation.
AB  - Bartter syndrome encompasses a variety of inheritable renal tubular transport
      disorders characterized by hypokalemia and hypochloremic metabolic alkalosis.
      Bartter syndrome Type III is caused by genetic alterations in the chloride
      channel kidney B (CLCNKB) gene and often presents in the first 2 years of life,
      known as classic Bartter syndrome. However, in rare cases Bartter syndrome Type
      III has an antenatal presentation with polyhydramnios, premature delivery and
      severe dehydration in the first weeks of life. Associations between congenital
      anomalies of the kidney and urinary tract and Bartter syndrome are extremely
      rare. This case report presents a girl with Bartter syndrome Type III due to a
      homozygous CLCNKB mutation and bilateral congenital anomalies of the kidney and
      urinary tract. In addition, we describe the antenatal presentation as well as its
      perinatal management.

PMID- 23164418
TI  - Schnitzler syndrome complicated by membranous nephropathy.
AB  - Schnitzler syndrome is a rare clinical entity characterized by the association of
      chronic urticarial rash and monoclonal immunoglobulin M gammopathy. A 62-year old
      male developed nephrotic syndrome with Schnitzler syndrome. A renal biopsy
      revealed mild thickening of the glomerular basement membrane with spikes and mild
      expansion of the mesangial matrix; prominent fine granular immunoglobulin G
      depositions were found along the capillary walls by immunofluorescence study and
      electron dense deposits were observed in the subepithelial spaces and in a part
      of mesangium by electron microscopically. The histological findings were
      compatible with secondary form of membranous nephropathy. To the best of our
      knowledge this is the first renal biopsy case of Schnitzler syndrome. With
      corticosteroid treatment chronic rash and proteinuria have disappeared, but
      immunoglobulin (IgM) paraprotein has been still present.

PMID- 23164419
TI  - Reversible left ventricular dysfunction and acute kidney injury in a patient with
      nonamyloid light chain deposition disease.
AB  - Non-amyloid light chain deposition disease (LCDD) is a rare entity that most
      commonly presents as proteinuria and/or renal dysfunction. We report on a patient
      who initially presented with acutely decompensated heart failure and subsequently
      developed nephrotic range proteinuria with attendant advanced renal dysfunction.
      The diagnosis of LCCD was made on renal biopsy.She was treated with five cycles
      of bortezomib and dexamethasone followed by cyclophosphamide priming for
      peripheral blood stem cell (PBSC) mobilization and auto logousstem cell
      transplant (ASCT). Four years later, she remains in very good partial response
      (VGPR) with a left ventricular ejection fraction (LVEF) of 58% and serum
      creatinine of 1.1 mg/dl. This observation supports the approach of aggressive
      management of patients with LCDD who have multiple organ failure.

PMID- 23164420
TI  - Comment on thrombotic microangiopathy induced by interferon-beta therapy.

PMID- 23164422
TI  - Effect of BMP-2 and/or BMP-9 on preosteoblasts attached to polycaprolactone
      functionalized by adhesive peptides derived from bone sialoprotein.
AB  - Biomaterials functionalized by adhesive peptides improve the cell-substratum
      interaction. However, their influence on the response of cells to growth factors
      is still poorly understood. We have shown that bone morphogenetic protein (BMP) 2
      activates the Smad pathway only in murine MC3T3-E1 preosteoblasts attached to
      polycaprolactone (PCL) film functionalized by RGD peptides derived from bone
      sialoprotein (pRGD). We have now analysed the way recombinant human BMP-2 and/or
      BMP-9 (0.38 nM) influence the signal transduction and differentiation of MC3T3-E1
      preosteoblasts attached to PCL-pRGD. While kinetics of MAPK activation were
      similar in cells treated by BMP-2 and BMP-9, different kinetics of Smad
      activation and beta-catenin stabilization were observed. BMP-2 induced Smad1/5/8
      phosphorylation within 0.5 and BMP-9 within 4 h, while the beta-catenin was lower
      at 2 h only in cells treated with BMP-9. However, both BMPs induced the
      translocation of phosphorylated Smad1/5/8 to the nucleus at 4 h and increased
      Dlx5, osterix and osteocalcin transcripts as well as alkaline phosphatase
      activity at 72 h. A BMP-2/BMP-9 combination that maintained the beta-catenin
      amount constant but reduced that of phosphorylated Smad within 4 h had quite
      similar effect than BMP-2 alone. It is therefore important to determine how
      biomimetic materials influence the response of cells to BMPs.

PMID- 23164421
TI  - A mesoporous silica nanoparticle--PEI--fusogenic peptide system for siRNA
      delivery in cancer therapy.
AB  - RNA interference (RNAi) is widely regarded as a promising technology for disease
      treatment, yet one major obstacle for its clinical application is the lack of
      efficient siRNA delivery vehicles. In this study, we described a magnetic
      mesoporous silica nanoparticles (M-MSNs)-based, polyelectrolyte
      (polyethylenimine, PEI) and fusogenic peptide (KALA)-functionalized siRNA
      delivery system (denoted as M-MSN_siRNA@PEI-KALA), which was highly effective for
      initiating target gene silencing both in vitro and in vivo. The construction of
      this delivery system began with the encapsulation of siRNA within the mesopores
      of M-MSNs, followed by the coating of PEI on the external surface of siRNA-loaded
      M-MSNs and the chemical conjugation of KALA peptides. The as-prepared delivery
      vehicles, with notable siRNA protective effect and negligible cytotoxicity, could
      be easily internalized into cells, readily escape from the endolysosomes and
      release the loaded siRNA into the cytoplasm. As a result, the knockdown of
      enhanced green fluorescent protein (EGFP) and vascular endothelial growth factor
      (VEGF) in tumor cells were observed, both with excellent RNAi efficiencies. In
      the following in vivo experiments, the intratumoral injection of M-MSN_VEGF
      siRNA@PEI-KALA significantly inhibited the tumor growth, possibly by the
      suppression of neovascularization in tumors. To sum up, we have established a
      highly effective MSNs-based delivery system, which has great potential to serve
      as therapeutic siRNA formulation for cancer treatment.

PMID- 23164423
TI  - Improving antiangiogenesis and anti-tumor activity of curcumin by biodegradable
      polymeric micelles.
AB  - For developing aqueous formulation and improving anti-tumor activity of curcumin
      (Cur), we prepared Cur encapsulated MPEG-PCL micelles by solid dispersion method
      without using any surfactants or toxic organic solvent. Cur micelles could be
      lyophilized into powder form without any cryoprotector or excipient, and the re
      dissolved Cur micelles are homogenous and stable. Molecular modeling study
      suggested that Cur tended to interact with PCL serving as a core embraced by PEG
      as a shell. After Cur was encapsulated into polymeric micelles, cytotoxicity and
      cellular uptake were both increased. Cur micelles had a stronger inhibitory
      effect on proliferation, migration, invasion, and tube formation of HUVECs than
      free Cur. Besides, Cur micelles showed a sustained in vitro release behavior and
      slow extravasation from blood vessels in transgenic zebrafish model. Embryonic
      angiogenesis and tumor-induced angiogenesis were both dramatically inhibited by
      Cur micelles in transgenic zebrafish model. Furthermore, Cur micelles were more
      effective in inhibiting tumor growth and prolonged survival in both subcutaneous
      and pulmonary metastatic LL/2 tumor models. In pharmacokinetic and tissue
      distribution studies, Cur micelles showed higher concentration and longer
      retention time in plasma and tumors. Our findings suggested that Cur micelles may
      have promising applications in pulmonary carcinoma therapy.

PMID- 23164424
TI  - Electrical coupling of isolated cardiomyocyte clusters grown on aligned
      conductive nanofibrous meshes for their synchronized beating.
AB  - Myocardial infarction is often associated with abnormalities in electrical
      function due to a massive loss of functioning cardiomyocytes. This work develops
      a mesh, consisting of aligned composite nanofibers of polyaniline (PANI) and
      poly(lactic-co-glycolic acid) (PLGA), as an electrically active scaffold for
      coordinating the beatings of the cultured cardiomyocytes synchronously. Following
      doping by HCl, the electrospun fibers could be transformed into a conductive form
      carrying positive charges, which could then attract negatively charged adhesive
      proteins (i.e. fibronectin and laminin) and enhance cell adhesion. During
      incubation, the adhered cardiomyocytes became associated with each other and
      formed isolated cell clusters; the cells within each cluster elongated and
      aligned their morphology along the major axis of the fibrous mesh. After culture,
      expression of the gap-junction protein connexin 43 was clearly observed
      intercellularly in isolated clusters. All of the cardiomyocytes within each
      cluster beat synchronously, implying that the coupling between the cells was
      fully developed. Additionally, the beating rates among these isolated cell
      clusters could be synchronized via an electrical stimulation designed to imitate
      that generated in a native heart. Importantly, improving the impaired heart
      function depends on electrical coupling between the engrafted cells and the host
      myocardium to ensure their synchronized beating.

PMID- 23164425
TI  - Effects of poly(L-lysine)-modified Fe3O4 nanoparticles on endogenous reactive
      oxygen species in cancer stem cells.
AB  - Intracellular reactive oxygen species (ROS) have been extensively shown to play
      an important role in the regulation of cell proliferation and cell cycle
      progression. The effects of endogenous ROS on the proliferation and
      differentiation of cancer stem cells (CSCs) have received increasing attention
      because of the unique properties of these cells that allow them to drive tumor
      growth and evade conventional cancer therapies. In this study, poly(L-Lysine)
      (PLL)-modified Fe(3)O(4) nanoparticles were synthesized to label CSCs derived
      from U251 glioblastoma multiform. A featured peroxidase-like activity within PLL
      modified Fe(3)O(4) nanoparticles that could greatly reduce intracellular H(2)O(2)
      activity was identified. We also found that PLL-modified Fe(3)O(4) nanoparticles
      could accelerate the progression of CSC cell cycle, probably due to the impaired
      activity of endogenous ROS in CSCs. These results show that growth and
      proliferation of CSCs could be promoted by Fe(3)O(4) nanocarriers in an ROS
      dependent manner, and Fe(3)O(4) nanocarriers may be suitable for certain tumor
      therapies as a drug delivery system.

PMID- 23164427
TI  - All about us, but never about us: the three-pronged potency of prejudice.
AB  - Three points that are implicit in Dixon et al.'s paradigm-challenging paper serve
      to make prejudice potent. First, prejudice reflects understandings of social
      identity - the relationship of "us" to "them" - that are shared within particular
      groups. Second, these understandings are actively promoted by leaders who
      represent and advance in-group identity. Third, prejudice is identified in out
      groups, not in-groups.

PMID- 23164426
TI  - Roles of microRNA on cancer cell metabolism.
AB  - Advanced studies of microRNAs (miRNAs) have revealed their manifold biological
      functions, including control of cell proliferation, cell cycle and cell death.
      However, it seems that their roles as key regulators of metabolism have drawn
      more and more attention in the recent years. Cancer cells display increased
      metabolic autonomy in comparison to non-transformed cells, taking up nutrients
      and metabolizing them in pathways that support growth and proliferation. MiRNAs
      regulate cell metabolic processes through complicated mechanisms, including
      directly targeting key enzymes or transporters of metabolic processes and
      regulating transcription factors, oncogenes / tumor suppressors as well as
      multiple oncogenic signaling pathways. MiRNAs like miR-375, miR-143, miR-14 and
      miR-29b participate in controlling cancer cell metabolism by regulating the
      expression of genes whose protein products either directly regulate metabolic
      machinery or indirectly modulate the expression of metabolic enzymes, serving as
      master regulators, which will hopefully lead to a new therapeutic strategy for
      malignant cancer. This review focuses on miRNA regulations of cancer cell
      metabolism,including glucose uptake, glycolysis, tricarboxylic acid cycle and
      insulin production, lipid metabolism and amino acid biogenesis, as well as
      several oncogenic signaling pathways. Furthermore, the challenges of miRNA-based
      strategies for cancer diagnosis, prognosis and therapeutics have been discussed.

PMID- 23164428
TI  - Respiratory symptoms and illnesses among brick kiln workers: a cross sectional
      study from rural districts of Pakistan.
AB  - BACKGROUND: Occupational risk factors are one of the major causes of respiratory
      illnesses and symptoms, and account for 13% of chronic obstructive pulmonary
      disease and 11% of asthma worldwide. Majority of brick kilns in Pakistan use wood
      and coal for baking the bricks which makes the brick kiln workers susceptible to
      high exposure of air pollution. This study was designed to describe frequency of
      chronic respiratory symptoms and illnesses and study the association between
      these symptoms and different types of work. METHODS: This was a questionnaire
      based cross sectional survey conducted among the brick kiln workers in Larkana
      and Dadu districts, Sindh, Pakistan. A total of 340 adult men were assessed using
      translated version of the American Thoracic Society Division of Lung Disease (ATS
      DLD) questionnaire. Logistic regression analysis was done to determine the
      relationship between various socio-demographic and occupational factors (age,
      education, type of work, number of years at work, smoking status), and the
      respiratory symptoms and illnesses (chronic cough, chronic phlegm, wheeze,
      Chronic Bronchitis and asthma). RESULTS: Results of the study show that 22.4%
      workers had chronic cough while 21.2% reported chronic phlegm. 13.8% had two or
      more attacks of shortness of breath with wheezing. 17.1% workers were suffering
      from Chronic Bronchitis while 8.2% reported physician diagnosed asthma. Amongst
      the non-smoking workers 8.9% had Chronic Bronchitis. Multivariate analysis found
      that workers involved in brick baking were more likely to have Chronic Bronchitis
      (OR= 3.7, 95% CI 1.1-11.6, p=<0.05) and asthma (OR= 3.9, 95% CI 1.01-15.5,
      p=<0.05) compared to those involved in carriage and placement work. CONCLUSION: A
      high frequency of respiratory symptoms and illnesses was observed among brick
      kiln workers. Age, nature of work and smoking were strong predictors of
      developing these symptoms and illnesses.

PMID- 23164429
TI  - Inter- and intra-subtype genotypic differences that differentiate Mycobacterium
      avium subspecies paratuberculosis strains.
AB  - BACKGROUND: Mycobacterium avium subspecies paratuberculosis (Map) is the
      aetiological agent of Johne's disease or paratuberculosis and is included within
      the Mycobacterium avium complex (MAC). Map strains are of two major types often
      referred to as 'Sheep' or 'S-type' and 'Cattle' or 'C-type'. With the advent of
      more discriminatory typing techniques it has been possible to further classify
      the S-type strains into two groups referred to as Type I and Type III. This study
      was undertaken to genotype a large panel of S-type small ruminant isolates from
      different hosts and geographical origins and to compare them with a large panel
      of well documented C-type isolates to assess the genetic diversity of these
      strain types. Methods used included Mycobacterial Interspersed Repetitive Units -
      Variable-Number Tandem Repeat analysis (MIRU-VNTR), analysis of Large Sequence
      Polymorphisms by PCR (LSP analysis), Single Nucleotide Polymorphism (SNP)
      analysis of gyr genes, Pulsed-Field Gel Electrophoresis (PFGE) and Restriction
      Fragment Length Polymorphism analysis coupled with hybridization to IS900 (IS900
      RFLP) analysis. RESULTS: The presence of LSP(A)4 and absence of LSP(A)20 was
      confirmed in all 24 Map S-type strains analysed. SNPs within the gyr genes
      divided the S-type strains into types I and III. Twenty four PFGE multiplex
      profiles and eleven different IS900-RFLP profiles were identified among the S
      type isolates, some of them not previously published. Both PFGE and IS900-RFLP
      segregated the S-type strains into types I and III and the results concurred with
      those of the gyr SNP analysis. Nine MIRU-VNTR genotypes were identified in these
      isolates. MIRU-VNTR analysis differentiated Map strains from other members of
      Mycobacterium avium Complex, and Map S-type from C-type but not type I from III.
      Pigmented Map isolates were found of type I or III. CONCLUSION: This is the
      largest panel of S-type strains investigated to date. The S-type strains could be
      further divided into two subtypes, I and III by some of the typing techniques
      (IS900-RFLP, PFGE and SNP analysis of the gyr genes). MIRU-VNTR did not divide
      the strains into the subtypes I and III but did detect genetic differences
      between isolates within each of the subtypes. Pigmentation is not exclusively
      associated with type I strains.

PMID- 23164430
TI  - Identification of SUMO targets by a novel proteomic approach in plants(F).
AB  - Post-translational modifications (PTMs) chemically and physically alter the
      properties of proteins, including their folding, subcellular localization,
      stability, activity, and consequently their function. In spite of their
      relevance, studies on PTMs in plants are still limited. Small Ubiquitin-like
      Modifier (SUMO) modification regulates several biological processes by affecting
      protein-protein interactions, or changing the subcellular localizations of the
      target proteins. Here, we describe a novel proteomic approach to identify SUMO
      targets that combines 2-D liquid chromatography, immunodetection, and mass
      spectrometry (MS) analyses. We have applied this approach to identify nuclear
      SUMO targets in response to heat shock. Using a bacterial SUMOylation system, we
      validated that some of the targets identified here are, in fact, labeled with
      SUMO1. Interestingly, we found that GIGANTEA (GI), a photoperiodic-pathway
      protein, is modified with SUMO in response to heat shock both in vitro and in
      vivo.

PMID- 23164431
TI  - T-lymphocyte CREB as a potential biomarker of response to antidepressant drugs.
AB  - Response to drug treatment of major depression is variable and biomarkers of
      response are needed. Cyclic AMP response element binding protein (CREB) is
      considered a key mediator of antidepressant drug effect. We studied CREB in T
      lymphocytes as a potential predictor of response to a selective serotonin
      reuptake inhibitor (SSRI) in 69 Korean depressed patients. We determined total
      CREB (tCREB), phosphorylated CREB (pCREB) and CRE-DNA binding using immunoblot
      and electrophoretic mobility shift assays, at baseline and after 6 wk treatment.
      Thirty-four healthy controls were also studied. The rate of response was 36 of 69
      cases (52%). Baseline levels of tCREB and pCREB were lower in the total depressed
      group compared to controls (p = 0.044 and p<0.001, respectively). Baseline tCREB
      values in responders were significantly reduced in comparison to non-responders
      and to controls. After 6 wk treatment, median values of change of all CREB
      measures were greater in responders (36) than in non-responders (33; p<0.001 for
      tCREB, p = 0.003 for pCREB, and p=0.072 for CRE-DNA binding). Similar but less
      robust changes in CREB variables distinguished remitters from non-remitters. The
      optimum value of baseline tCREB predicted response with a positive predicted
      value of 0.778 [21/27; 95% confidence intervals (CI) 0.621-0.935], negative
      predictive value of 0.643 (27/42; 95% CI 0.498-0.788) and accuracy of 0.695
      (48/69; 95% CI 0.586-0.804). Patients with low baseline tCREB had a significantly
      greater rate of response (78%) than patients with high baseline tCREB (36%), p <
      0.001. Moreover, the greatest changes in tCREB with treatment were observed in
      subjects who did respond. This preliminary study suggests that T-lymphocytic CREB
      biomarkers are reduced in depressed patients and may assist in the prediction of
      response to SSRI drugs in depression.

PMID- 23164432
TI  - Latent class analysis of the diagnostic characteristics of PCR and conventional
      bacteriological culture in diagnosing intramammary infections caused by
      Staphylococcus aureus in dairy cows at dry off.
AB  - BACKGROUND: Staphylococcus aureus is one of the most common causes of
      intramammary infections in dairy cows at dry off. Reliable identification is
      important for disease management on herd level and for antimicrobial treatment of
      infected animals. Our objective was to evaluate the test characteristics of
      PathoProof TM Mastitis PCR Assay and bacteriological culture (BC) in diagnosing
      bovine intramammary infections caused by S. aureus at dry off at different PCR
      cycle threshold (Ct)-value cut-offs. METHODS: Sterile quarter samples and non
      sterile composite samples from 140 animals in seven herds were collected in
      connection with the dairy herd improvement (DHI) milk recording. All quarter
      samples were analyzed using BC whereas all composite samples were analyzed with
      PathoProof TM Mastitis PCR Assay. Latent class analysis was used to estimate test
      properties for PCR and BC in the absence of a perfect reference test. The
      population was divided into two geographically divided subpopulations and the Hui
      Walter 2-test 2-populations model applied to estimate Se, Sp for the two tests,
      and prevalence for the two subpopulations. RESULTS: The Se for PCR increased with
      increasing Ct-value cut-off, accompanied by a small decrease in Sp. For BC the Se
      decreased and Sp increased with increasing Ct-value cut-off. Most optimal test
      estimates for the real-time PCR assay were at a Ct-value cut-off of 37; 0.93 [95%
      posterior probability interval (PPI) 0.60-0.99] for Se and 0.95 [95% PPI 0.95
      0.99] for Sp. At the same Ct-value cut-off, Se and Sp for BC were 0.83 [95% PPI
      0.66-0.99] and 0.97 [95% PPI 0.91-0.99] respectively. Depending on the chosen PCR
      Ct-value cut-off, the prevalence in the subpopulations varied; the prevalence
      increased with increasing PCR Ct-value cut-offs. CONCLUSION: Neither BC nor real
      time PCR is a perfect test in detecting IMI in dairy cows at dry off. The changes
      in sensitivity and prevalence at different Ct-value cut-offs for both PCR and BC
      may indicate a change in the underlying disease definition. At low PCR Ct-value
      cut-offs the underlying disease definition may be a truly/heavily infected cow,
      whereas at higher PCR Ct-value cut-offs the disease definition may be a S. aureus
      positive cow.

PMID- 23164433
TI  - Comment on "Towards ecologically relevant targets for river pollutant loads to
      the Great Barrier Reef" by F.J. Kroon.

PMID- 23164434
TI  - Modelling biofilm-induced formation damage and biocide treatment in subsurface
      geosystems.
AB  - Biofilm growth in subsurface porous media, and its treatment with biocides
      (antimicrobial agents), involves a complex interaction of biogeochemical
      processes which provide non-trivial mathematical modelling challenges. Although
      there are literature reports of mathematical models to evaluate biofilm tolerance
      to biocides, none of these models have investigated biocide treatment of biofilms
      growing in interconnected porous media with flow. In this paper, we present a
      numerical investigation using a pore network model of biofilm growth, formation
      damage and biocide treatment. The model includes three phases (aqueous, adsorbed
      biofilm, and solid matrix), a single growth-limiting nutrient and a single
      biocide dissolved in the water. Biofilm is assumed to contain a single species of
      microbe, in which each cell can be a viable persister, a viable non-persister, or
      non-viable (dead). Persisters describe small subpopulation of cells which are
      tolerant to biocide treatment. Biofilm tolerance to biocide treatment is
      regulated by persister cells and includes 'innate' and 'biocide-induced' factors.
      Simulations demonstrate that biofilm tolerance to biocides can increase with
      biofilm maturity, and that biocide treatment alone does not reverse biofilm
      induced formation damage. Also, a successful application of biological
      permeability conformance treatment involving geologic layers with flow
      communication is more complicated than simply engineering the attachment of
      biofilm-forming cells at desired sites.

PMID- 23164435
TI  - Dilated cardiomyopathy due to hypocalcaemic rickets: is it always a reversible
      condition?
AB  - Nutritional rickets is still occasionally found in high-income countries,
      especially in populations at risk, and induced hypocalcaemia is a rare but
      possible cause of dilated cardiomyopathy. Although rare, physicians need to
      consider nutritional rickets in the differential diagnosis of hypocalcaemia
      cardiac failure, especially in high-risk populations such as immigrants. Despite
      being a reversible condition, the prognosis depends on the severity and time of
      diagnosis. We report two cases of exclusively breastfed infants with congestive
      cardiac failure due to hypokinetic dilated cardiomyopathy who had completely
      different outcomes. This report supports the need for prevention of this
      deficiency and underlies the role of vitamin D supplementation.

PMID- 23164436
TI  - History of total ankle replacement.
AB  - Attempts at ankle replacement have existed for at least 50 years. Time has
      essentially eliminated constrained, cemented, first-generation ankle
      replacements. Although some two-component, more anatomic, designs are still used
      with varying success, three-component "mobile bearing" ankle prostheses are
      winning the race of evolution. Not only have implants change over the years, but
      also the patients and surgeons. Surgeons specialize, improving their surgical
      outcomes and expanding the indications for total ankle replacement in technically
      demanding complex ankles. High-demand, younger patients, but also obese ones, are
      potential candidates for a total ankle replacement. This article provides a
      review of the history of total ankle replacement.

PMID- 23164437
TI  - Controversies in total ankle replacement.
AB  - Although there exist general guidelines regarding which patients are "suitable"
      candidates for total ankle replacement, these guidelines tend to be very
      conservative, much like those of knee and hip replacement from decades ago. There
      are also no direct comparison studies of one total ankle replacement design with
      another. Because of the paucity of data, surgeons are left to surmise the opinion
      based on limited studies, as well as industry-sponsored data and advertising
      material. This article examines several key, controversial issues that apply to
      total ankle replacement. Recommendations and points for thought are provided.

PMID- 23164438
TI  - Techniques for managing varus and valgus malalignment during total ankle
      replacement.
AB  - The ultimate goal of primary total ankle replacement is to provide a well
      balanced soft-tissue envelope around a well-aligned, well-fixated implant. Some
      surgeons have emphasized that good outcomes in total ankle replacement are more
      dependent on ligament balancing, along with the procedure itself, than the extent
      of preoperative coronal deformity in the ankle. Thus, it is imperative that the
      surgeon be familiar with additional procedures to address the varus, valgus, and
      other associated deformities commonly encountered in primary total ankle
      replacement.

PMID- 23164439
TI  - The INBONE II Total Ankle System.
AB  - The INBONE II Total Ankle System consists of modular intramedullary stem pieces
      that are supported by a tibial tray spanning the anterior and posterior tibial
      cortices. The original INBONE talar component was broad and saddle-shaped whereas
      the INBONE II design is sulcus-shaped. Both talar components have a modular stem;
      the INBONE II design also has 2 anterior pegs. This article provides a detailed
      review of the surgical technique for implantation of the INBONE II and
      perioperative insight into patient care.

PMID- 23164440
TI  - Salto Talaris fixed-bearing total ankle replacement system.
AB  - The Salto Talaris total ankle replacement is an anatomically designed fixed
      bearing prosthesis available in the United States based on the successful design
      of the mobile-bearing Salto prosthesis available outside the United States. The
      original mobile-bearing design was modified and the mobile-bearing was
      transferred to the precision instrumentation at the trial phase evaluation.
      Instrumentation and technique allow the surgeon to determine the functional joint
      axis before final implantation. The Salto Talaris total ankle replacement design
      blends minimal bone resection and optimizes surface area, cortical contact, and
      ultra-high molecular weight polyethylene conformity. The authors present an
      overview of the Salto Talaris total ankle replacement surgical technique and
      pearls for successful application.

PMID- 23164441
TI  - Agility to INBONE: anterior and posterior approaches to the difficult revision
      total ankle replacement.
AB  - Total ankle replacement is now acknowledged as a viable alternative to ankle
      arthrodesis for end-stage ankle arthritis. The authors present a series of 14
      patients who were converted from the Agility total ankle replacement to an INBONE
      total ankle replacement. This report is unique in that anterior and posterior
      approaches are discussed and detailed. Although the authors present successful
      conversion of the Agility total ankle replacement to an INBONE total ankle
      replacement, the difficulty of this procedure is demonstrated by the high
      complication rate and 2 early failures.

PMID- 23164442
TI  - Polyarticular sepsis originating from a prior total ankle replacement.
AB  - As more primary total ankle arthroplasty procedures are being performed, an
      increased awareness of potential complications is needed. One such complication
      is a deep periprosthetic infection which, if left untreated, can quickly evolve
      into a limb-threatening infection. In rare instances the infection can propagate
      into a polyarticular joint sepsis and become life threatening. By adhering to the
      basic principles of medical stabilization and surgical intervention in a staged
      approach with adequate wide resection of all necrotic tissue, this potentially
      life-threatening situation can be managed and a functional limb can be restored.

PMID- 23164443
TI  - Salvage of a failed DePuy Alvine Total Ankle Prosthesis with Agility LP custom
      stemmed tibia and talar components.
AB  - This article presents a procedure whereby a second-phase design DePuy Alvine
      Total Ankle Prosthesis underwent revision to an Agility LP custom-designed
      stemmed tibial and talar component total ankle replacement system. The rationale
      for this procedure, the process of developing the custom components, the
      operative sequence of events, and recovery course are presented in detail. Causes
      for concern regarding subsequent revision, should this be required, are raised.

PMID- 23164444
TI  - Diabetic calcaneal fractures.
AB  - Calcaneal fractures among the diabetic population are severe and complex injuries
      that warrant careful evaluation in an effort to carry out adequate conservative
      or surgical management. The complication rates associated with diabetic fracture
      management are increased and may include poor wound healing, deep infection,
      malunion, and Charcot neuroarthropathy, each of which can pose a risk for limb
      loss. The significant surgery-associated morbidity accompanying diabetic
      calcaneal fractures has led to improved methods of calcaneal fracture management.
      This article reviews the overall management of diabetic calcaneal fractures,
      complications, and outcomes.

PMID- 23164445
TI  - Primary total ankle replacement.

PMID- 23164446
TI  - Contemporary total ankle replacement devices. Preface.

PMID- 23164447
TI  - What's so crummy 'bout peace, love, and understanding?
AB  - The target article challenges standard approaches to prejudice reduction, warning
      that they may inure people to inequality and deflect them from seeking collective
      solutions to it. I argue that the collective action approach has its own risks
      and limitations and that standard contact and common identity approaches may
      complement rather than work against it.

PMID- 23164448
TI  - The toxic effects of mobile phone radiofrequency (940 MHz) on the structure of
      calf thymus DNA.
AB  - Currently, the biological effects of nonionizing electromagnetic fields (EMFs)
      including radiofrequency (RF) radiation have been the subject of numerous
      experimental and theoretical studies. The aim of this study is to evaluate the
      possible biological effects of mobile phone RF (940 MHz, 15 V/m and SAR=40 mW/kg)
      on the structure of calf thymus DNA (ct DNA) immediately after exposure and 2 h
      after 45 min exposure via diverse range of spectroscopic instruments. The UV-vis
      and circular dichroism (CD) experiments depict that mobile phone EMFs can
      remarkably cause disturbance on ct DNA structure. In addition, the DNA samples,
      immediately after exposure and 2 h after 45 min exposure, are relatively
      thermally unstable compared to the DNA solution, which was placed in a small
      shielded box (unexposed ct DNA). Furthermore, the exposed DNA samples (the DNA
      samples that were exposed to 940 MHz EMF) have more fluorescence emission when
      compared with the unexposed DNA, which may have occurred attributable to
      expansion of the exposed DNA structure. The results of dynamic light scattering
      (DLS) and zeta potential experiments demonstrate that RF-EMFs lead to increment
      in the surface charge and size of DNA. The structure of DNA immediately after
      exposure is not significantly different from the DNA sample 2 h after 45 min
      exposure. In other words, the EMF-induced conformational changes are
      irreversible. Collectively, our results reveal that 940 MHz can alter the
      structure of DNA. The displacement of electrons in DNA by EMFs may lead to
      conformational changes of DNA and DNA disaggregation. Results from this study
      could have an important implication on the health effects of RF-EMFs exposure. In
      addition, this finding could proffer a novel strategy for the development of next
      generation of mobile phone.

PMID- 23164449
TI  - Olfactory recovery of wild yellow perch from metal contaminated lakes.
AB  - Fish depend on their sense of smell for a wide range of vital life processes
      including finding food, avoiding predators and reproduction. Various
      contaminants, including metals, can disrupt recognition of chemical information
      in fish at very low concentrations. Numerous studies have investigated metal
      effects on fish olfaction under controlled laboratory conditions. However, few
      have measured olfactory acuity using wild fish in source water. In this study, we
      used electro-olfactography (EOG) to measure the olfactory acuity of wild yellow
      perch (Perca flavescens) from a clean lake (Geneva Lake) and two metal
      contaminated lakes (Ramsey and Hannah lakes) from Sudbury, ON, in their own lake
      water or in water from the other lakes. The results showed that fish from the
      clean lake had a greater olfactory acuity than those from metal contaminated
      lakes when fish were tested in their own lake water. However, when fish from the
      clean lake were held for 24h in water from each of the two contaminated lakes
      their olfactory acuity was diminished. On the other hand, fish from the
      contaminated lakes held for 24h in clean lake water showed a significant
      olfactory recovery relative to that measured in their native lake water. These
      results show that although fish from a clean lake demonstrated impaired olfaction
      after only 24h in metal-contaminated water, fish from metal contaminated lakes
      showed a rapid olfactory recovery when exposed to clean water for only hours.

PMID- 23164450
TI  - SSH gene expression profile of Eisenia andrei exposed in situ to a naturally
      contaminated soil from an abandoned uranium mine.
AB  - The effects of the exposure of earthworms (Eisenia andrei) to contaminated soil
      from an abandoned uranium mine, were assessed through gene expression profile
      evaluation by Suppression Subtractive Hybridization (SSH). Organisms were exposed
      in situ for 56 days, in containers placed both in a contaminated and in a non
      contaminated site (reference). Organisms were sampled after 14 and 56 days of
      exposure. Results showed that the main physiological functions affected by the
      exposure to metals and radionuclides were: metabolism, oxireductase activity,
      redox homeostasis and response to chemical stimulus and stress. The relative
      expression of NADH dehydrogenase subunit 1 and elongation factor 1 alpha was also
      affected, since the genes encoding these enzymes were significantly up and down
      regulated, after 14 and 56 days of exposure, respectively. Also, an EST with
      homology for SET oncogene was found to be up-regulated. To the best of our
      knowledge, this is the first time that this gene was identified in earthworms and
      thus, further studies are required, to clarify its involvement in the toxicity of
      metals and radionuclides. Considering the results herein presented, gene
      expression profiling proved to be a very useful tool to detect earthworms
      underlying responses to metals and radionuclides exposure, pointing out for the
      detection and development of potential new biomarkers.

PMID- 23164451
TI  - Juvenile systemic lupus erythematosus onset patterns in Vietnamese children: a
      descriptive study of 45 children.
AB  - BACKGROUND: Incidence and disease pattern of childhood-onset SLE is reported to
      differ among ethnic groups. METHODS: To describe disease pattern and 6 month
      follow-up in a referral based cohort of 45 Vietnamese children with SLE. Forty
      five children who were subsequently diagnosed to have systemic lupus
      erythematosus (f/m = 4/1) were referred to the Ho Chi Minh City Children's
      Hospital No.1 during a 12-month period in 2009. RESULTS: The mean age at
      diagnosis was 12.8 years (SD = 2.5). Thirty-seven (82%) fulfilled criteria for
      lupus nephritis (LN). At diagnosis, impressively high SLEDAI and ECLAM scores
      were recorded (mean and SD), 23.8 (11.6) and 6 (2.3), respectively. The mean
      renal SLEDAI score was 8.2. The mean haemoglobin (g/dL, SD) was 8.5 (2.1). The
      Coombs test was positive in 30 of 36 children (83%). The mean plasma creatinine
      was 0.98 (SD 1.2) and mean Westergren sedimentation rate was 83.6 (SD 37.4). The
      patient age at diagnosis was positively correlated to the SLEDAI (p = 0.034) and
      ECLAM (p = 0.022). At 6 month follow-up of the 45 children, 15 patients were in
      complete remission, 5 were in partial remission, 6 had stable disease, 3 had
      relapsed, 3 had evolving disease, 2 had ongoing resistant disease and 4 had died.
      Seven patients were lost to follow-up. A second renal biopsy showed an improved
      ISN class in 13 of 15; in 2 cases the ISN class remained unchanged. CONCLUSIONS:
      Forty-five Vietnamese children with SLE were referred to Ho Chi Minh Children's
      Hospital No. 1 during a16 month period from 2008-2009. These patients had a
      strikingly high prevalence of Coombs positive anaemia, a high prevalence of lupus
      nephritis, and very high SLEDAI and ECLAM scores at the time of diagnosis. While
      there may be referral biases, our Vietnamese SLE patients appear to have severe
      disease upon presentation but do reasonably well in the short-term.

PMID- 23164452
TI  - DNAGear--a free software for spa type identification in Staphylococcus aureus.
AB  - BACKGROUND: Staphylococcus aureus is both human commensal and an important human
      pathogen, responsible for community-acquired and nosocomial infections ranging
      from superficial wound infections to invasive infections, such as osteomyelitis,
      bacteremia and endocarditis, pneumonia or toxin shock syndrome with a mortality
      rate up to 40%. S. aureus reveals a high genetic polymorphism and detecting the
      genotypes is extremely useful to manage and prevent possible outbreaks and to
      understand the route of infection. One of current and expanded typing method is
      based on the X region of the spa gene composed of a succession of repeats of 21
      to 27 bp. More than 10000 types are known. Extracting the repeats is impossible
      by hand and needs a dedicated software. Unfortunately the only software on the
      market is a commercial program from Ridom. FINDINGS: This article presents
      DNAGear, a free and open source software with a user friendly interface written
      all in Java on top of NetBeans Platform to perform spa typing, detecting new
      repeats and new spa types and synchronizing automatically the files with the open
      access database. The installation is easy and the application is platform
      independent. In fact, the SPA identification is a formal regular expression
      matching problem and the results are 100% exact. As the program is using Java
      embedded modules written over string manipulation of well established algorithms,
      the exactitude of the solution is perfectly established. CONCLUSIONS: DNAGear is
      able to identify the types of the S. aureus sequences and detect both new types
      and repeats. Comparing to manual processing, which is time consuming and error
      prone, this application saves a lot of time and effort and gives very reliable
      results. Additionally, the users do not need to prepare the forward-reverse
      sequences manually, or even by using additional tools. They can simply create
      them in DNAGear and perform the typing task. In short, researchers who do not
      have commercial software will benefit a lot from this application.

PMID- 23164453
TI  - Role of the small GTPase Rab27a during herpes simplex virus infection of
      oligodendrocytic cells.
AB  - BACKGROUND: The morphogenesis of herpes simplex virus type 1 (HSV-1) comprises
      several events, of which some are not completely understood. It has been shown
      that HSV-1 glycoproteins accumulate in the trans-Golgi network (TGN) and in TGN
      derived vesicles. It is also accepted that HSV-1 acquires its final morphology
      through a secondary envelopment by budding into TGN-derived vesicles coated with
      viral glycoproteins and tegument proteins. Nevertheless, several aspects of this
      process remain elusive. The small GTPase Rab27a has been implicated in regulated
      exocytosis, and it seems to play a key role in certain membrane trafficking
      events. Rab27a also seems to be required for human cytomegalovirus assembly.
      However, despite the involvement of various Rab GTPases in HSV-1 envelopment,
      there is, to date, no data reported on the role of Rab27a in HSV-1 infection.
      RESULTS: Herein, we show that Rab27a colocalized with GHSV-UL46, a tegument
      tagged green fluorescent protein-HSV-1, in the TGN. In fact, this small GTPase
      colocalized with viral glycoproteins gH and gD in that compartment. Functional
      analysis through Rab27a depletion showed a significant decrease in the number of
      infected cells and viral production in Rab27a-silenced cells. CONCLUSIONS:
      Altogether, our results indicate that Rab27a plays an important role in HSV-1
      infection of oligodendrocytic cells.

PMID- 23164455
TI  - Genomic distribution of the small multidrug resistance protein EmrE over 29
      Escherichia coli strains reveals two forms of the protein.
AB  - Analysis of the genomes of 29 Escherichia coli strains revealed two different
      versions of the EmrE protein, a member of the small multidrug resistance family.
      The versions are different in length and contain 110 residues (EMRE(110)) and 165
      residues (EMRE(165)). The N-terminal extension found in the longer sequence has
      the properties of a signal sequence, i.e. contains at the extreme N-terminus a
      hydrophobic region followed by a predicted cleavage site. Analysis of the genetic
      context of the genes in the different strains showed that all of the genes
      encoding EMRE(165) had the same context, whereas the genes encoding EMRE(110)
      were distributed over four different, but similar, contexts. The different
      genetic contexts corresponded to the branching of the phylogenetic tree of the
      emrE genes. Membrane topology studies using translational fusions with the two
      reporter proteins alkaline phosphatase and green fluorescent protein showed the
      well-described dual topology mode of insertion of EMRE(110). In contrast, but in
      line with the presence of the signal sequence, EMRE(165) was inserted in a single
      orientation into the membrane, with the C-terminus in the periplasm. The N
      terminal region was removed from the protein after insertion into the membrane.
      In contrast to cells expressing EMRE(110), cells expressing only mature EMRE(165)
      were not able to grow on plates containing ethidium bromide. The reults suggest
      that if dimers were formed from EMRE(165) monomers with the same orientation in
      the membrane, they would not be active in drug extrusion.

PMID- 23164454
TI  - Chronic valproate attenuates some, but not all, facets of mania-like behaviour in
      mice.
AB  - Bipolar disorder (BD) mania is a psychiatric disorder with multifaceted symptoms.
      Development of targeted treatments for BD mania may benefit from animal models
      that mimic multiple symptoms, as opposed to hyperactivity alone. Using the
      reverse-translated multivariate exploratory paradigm, the behavioural pattern
      monitor (BPM), we reported that patients with BD mania exhibit hyperactivity as
      well as increased specific exploration and more linear movements through space.
      This abnormal profile is also observed in mice with reduced function of the
      dopamine transporter (DAT) through either constitutive genetic [knockdown (KD)]
      or acute pharmacological (GBR12909) means. Here, we assessed the pharmacological
      predictive validity of these models by administering the BD-treatment valproic
      acid (VPA) for 28 d. After 1.5% VPA- or regular-chow treatment for 28 d, C57BL/6J
      mice received GBR12909 (9 mg/kg) or saline and were tested in the BPM. Similarly,
      DAT KD and wild type (WT) littermates were treated with VPA-chow and tested in
      the BPM. GBR12909-treated and DAT KD mice on regular chow were hyperactive,
      exhibited increased specific exploration and moved in straighter patterns
      compared to saline-treated and WT mice respectively. Chronic 1.5% VPA-chow
      treatment resulted in therapeutic concentrations of VPA and ameliorated
      hyperactivity in both models, while specific exploration and behavioural
      organization remained unaffected. Hence, the mania-like profile of mice with
      reduced functional DAT was partially attenuated by chronic VPA treatment,
      consistent with the incomplete symptomatic effect of VPA treatment in BD
      patients. Both DAT models may help to identify therapeutics that impact the full
      spectrum of BD mania.

PMID- 23164457
TI  - Left ventricular mass by echocardiographic measures in children and adolescents.
AB  - BACKGROUND: Recent evidence in adults suggests that left ventricular mass
      measured as left ventricular mass/height predicts cardiovascular morbidity and
      mortality better than the two widely used indices, left ventricular mass/body
      surface area and left ventricular mass/height Standards of left ventricular
      mass/height have not been reported in children, for whom, owing to lack of
      significant cardiovascular morbidity and mortality, body mass index has
      traditionally been used as a potential cardiovascular risk factor. METHODS: In
      this retrospective study, 692 clinically normal children aged 1 day to 18 years
      underwent detailed echocardiographic assessment to assess whether any of the left
      ventricular mass indices--left ventricular mass/height, left ventricular
      mass/body surface area, and left ventricular mass/height--are associated with
      obesity as measured by body mass index. Correlations, t-tests, and linear
      regressions were used for statistical testing. RESULTS: Left ventricular
      mass/height was better correlated (R2 = 0.36) with body mass index than left
      ventricular mass/body surface area (R2 = 0.179) and left ventricular mass/height
      (R2 = 0.006), although all three dependent variables show a significant
      correlation (p < 0.035). In addition, a higher percentage of obese patients were
      noted to have elevated left ventricular mass as measured by left ventricular
      mass/height than by the other two methods. CONCLUSIONS: Left ventricular
      mass/height is a reliable indicator of obesity associated left ventricular
      hypertrophy. Left ventricular mass/height can be used conveniently during
      transitions from youth to adults for long-term follow-up. These findings support
      the importance of including left ventricular mass/height in future studies of
      cardiovascular risks and preventive strategies in children and adolescents.

PMID- 23164456
TI  - Cardiac rehabilitation may not provided a quality of life benefit in coronary
      artery disease patients.
AB  - BACKGROUND: Improvements in patient-reported health-related quality of life
      (HRQoL) are important goals of cardiac rehabilitation (CR). In patients
      undergoing coronary angiography for angina and with documented coronary artery
      disease (CAD), the present study compared HRQoL over 6 months in CR participants
      and non-participants. Clinical predictors of CR participants were also assessed.
      METHODS: A total of 221 consecutive patients undergoing angiography for angina
      with documented CAD and who were eligible for a CR program were recruited. CR
      participants were enrolled in a six-week Phase II outpatient CR course (31%, n =
      68) within 2 months following angiography and the non-participants were included
      as a control. At baseline (angiography), one and six months post angiography,
      clinical and HRQoL data were obtained including the Short Form-36 (SF-36) and the
      Seattle Angina Questionnaire (SAQ). The response rate for the HRQoL assessment
      was 68% (n = 150). Cross sectional comparisons were age-adjusted and performed
      using logistic or linear regression as appropriate. Longitudinal changes in HRQoL
      were assessed using least squares regression. Finally, a multiple logistic
      regression was fitted with CR participant as the final outcome. RESULTS: At
      angiography, the CR non-participants were older, and age-adjusted analyses
      revealed poorer physical (angina limitation: 54 +/- 25 versus 64 +/- 22, p <0.05)
      and mental HRQoL (significant psycho-social distress: 62%, n = 95 versus 47%, n =
      32, p <0.05) compared to the CR participants. In addition, the CR participants
      were more likely to have undergone angiography for myocardial infarction (OR =
      2.8, 95% CI 1.5-5.3, p = 0.001). By six months, all patients showed an
      improvement in HRQoL indices, however the rate of improvement did not differ
      between the controls and CR participants. CONCLUSION: Following angiography, CAD
      patients reported improvements in both generic and disease-specific HRQoL,
      however CR participation did not influence this outcome. This may be explained by
      biases in CR enrollment, whereby acute patients, who may be less limited in HRQoL
      compared to stable, chronic patients, are targeted for CR participation. Further
      investigation is required so CR programs maximize the quality of life benefits to
      all potential CR patients.

PMID- 23164458
TI  - [The challenge of anal pathology related to human papillomavirus in human
      immunodeficiency virus-infected patients].

PMID- 23164459
TI  - Vascular endothelial growth factor receptor 2 gene (KDR) polymorphisms and
      expression levels in depressive disorder.
AB  - Recent research findings suggest that vascular endothelial growth factor (VEGF)
      participates in the development of depressive disorder. VEGF is involved in
      neurogenesis and neuroprotection processes, mediated by vascular endothelial
      growth factor receptor 2 (VEGFR2). VEGFR2 also plays a role in angiogenesis, a
      process related to neurogenesis and other biological processes. We examined
      VEGFR2 (KDR) gene polymorphism, mRNA expression levels, as well as VEGFR2 protein
      levels in 268 patients diagnosed with a recurrent depressive disorder (rDD) using
      the ICD-10 criteria, and in 200 healthy controls. Genotyping and gene expression
      level analysis was performed using polymerase chain reaction (PCR)-based methods.
      An Enzyme-Linked Immunosorbent Assay (ELISA) was used for measurement of KDR
      protein levels. Our study found that distribution of KDR polymorphism +1416T/A
      differs significantly in patients with rDD when compared to healthy subjects,
      while A allele and AA genotype are risk factors for rDD. KDR mRNA and protein
      expression are higher in patients with rDD. We also observed a significant
      association between the -271A/G variant and gene and protein levels. Our study is
      the first to demonstrate that the KDR gene may serve as a novel genetic marker
      that could participate in the etiology of rDD. This new pathway may play a role
      in the inflammatory pathophysiology of depression.

PMID- 23164460
TI  - Seasonality of mood and behavior in the Old Order Amish.
AB  - BACKGROUND/OBJECTIVE: We examined seasonality and winter seasonal affective
      disorder (SAD) in the Old Order Amish of Lancaster County, Pennsylvania, a unique
      population that prohibits use of network electric light in their homes. METHODS:
      We estimated SAD using the seasonal pattern assessment questionnaire (SPAQ) in
      1306 Amish adults and compared the frequencies of SAD and total SAD (i.e.,
      presence of either SAD or subsyndromal-SAD) between men and women, young and old,
      and awareness of (ever vs. never heard about) SAD. Heritability of global
      seasonality score (GSS) was estimated using the maximum likelihood method,
      including a household effect to capture shared environmental effects. RESULTS:
      The mean (+/-SD) GSS was 4.36 (+/-3.38). Prevalence was 0.84% (95% CI: 0.36-1.58)
      for SAD and 2.59% (95% CI: 1.69-3.73) for total SAD. Heritability of GSS was
      0.14+/-0.06 (SE) (p=0.002) after adjusting for age, gender, and household
      effects. LIMITATIONS: Limitations include likely overestimation of the rates of
      SAD by SPAQ, possible selection bias and recall bias, and limited
      generalizability of the study. CONCLUSIONS: In the Amish, GSS and SAD prevalence
      were lower than observed in earlier SPAQ-based studies in other predominantly
      Caucasian populations. Low heritability of SAD suggests dominant environmental
      effects. The effects of awareness, age and gender on SAD risk were similar as in
      previous studies. Identifying factors of resilience to SAD in the face of
      seasonal changes in the Amish could suggest novel preventative and therapeutic
      approaches to reduce the impact of SAD in the general population.

PMID- 23164461
TI  - The cost of depression - a cost analysis from a large database.
AB  - BACKGROUND: Depression poses a serious economic problem. We performed a cost-of
      illness study using data from a German health insurance company to determine
      which costs are unique to that disease. METHODS: The analysis included every
      adult and continuously insured person. Using claims data from 2007 to 2009, we
      calculated the costs incurred by persons with depression, including services
      provided for inpatient and outpatient care, drugs and psychiatric outpatient
      clinics. Subgroup analyses were done using demographic and disease-specific
      variables. Longitudinal predictors of depression-related costs were obtained
      through a generalized estimating equations (GEE) analysis. RESULTS: This
      investigation involved 117,220 persons. Mean annual depression-specific costs per
      person were ?458.9, with those costs decreasing over the study period. The main
      cost component (43.9% of the total) was inpatient care. It was found that persons
      with a severe course of disease and unemployed persons are more costly than other
      persons. The GEE analysis revealed that gender, age, residency within an urban
      area, occupational status and the type of diagnosis had a significant impact on
      these costs. LIMITATIONS: Due to data constraints, we were unable to include all
      cost categories that might be related to depression and we had no control group
      of persons without depression. CONCLUSIONS: Due to the influence of the severity
      of the disease on costs, effective treatment strategies are important in order to
      prevent a progression of the disease and an increase in costs.

PMID- 23164462
TI  - Personal and familial correlates of bipolar (BP)-I disorder in children with a
      diagnosis of BP-I disorder with a positive child behavior checklist (CBCL)-severe
      dysregulation profile: a controlled study.
AB  - BACKGROUND: Although the DSM-IV provides explicit criteria for the diagnosis of
      BP-I disorder, this is a complex diagnosis that requires high levels of clinical
      expertise. Previous work shows children with a unique profile of the CBCL of high
      scores (2SD) on the attention problems (AP), aggressive behavior (AGG), and
      anxious-depressed (AD) (A-A-A) subscales are more likely than other children to
      meet criteria for BP-I disorder in both epidemiological and clinical samples.
      However, since not all BP-I disorder children have a positive profile questions
      remain as to its informativeness, particularly in the absence of an expert
      diagnostician. METHODS: Analyses were conducted comparing personal and familial
      correlates of BP-I disorder in 140 youth with a structured interview and an
      expert clinician based DSM-IV diagnosis of BP-I disorder with (N=80) and without
      (N=60) a positive CBCL- Severe Dysregulation profile, and 129 controls of similar
      age and sex without ADHD or a mood disorder. Subjects were comprehensively
      assessed with structured diagnostic interviews and wide range of functional
      measures. We defined the CBCL-severe dysregulation profile as an aggregate cut
      off score of >= 210 on the A-A-A scales. RESULTS: BP-I probands with and without
      a positive CBCL-severe dysregulation profile significantly differed from Controls
      in patterns of psychiatric comorbidity, psychosocial and psychoeducational
      dysfunction, and cognitive deficits, as well as in their risk for BP-I disorder
      in first degree relatives. LIMITATIONS: Because the sample was referred and
      largely Caucasian, findings may not generalize to community samples and other
      ethnic groups. CONCLUSION: A positive CBCL-severe dysregulation profile
      identifies a severe subgroup of BP-I disorder youth.

PMID- 23164463
TI  - Should criteria be specified for depressive disorder not otherwise specified?
AB  - BACKGROUND: Many patients have clinically significant symptoms of depression that
      do not meet the DSM-IV diagnostic thresholds for major depressive disorder (MDD)
      or dysthymic disorder. DSM-IV does not specify criteria for depressive disorder
      not otherwise specified (DDNOS). While it is not surprising that research on
      subthreshold depression has used diverse criteria, some consensus has emerged to
      define minor depression analogous to MDD, though requiring fewer than the 5
      symptoms required to diagnose MDD. In the present report from the Rhode Island
      Methods to Improve Diagnostic Assessment and Services (MIDAS) project, we
      examined how many patients diagnosed with DDNOS met the DSM-IV proposed research
      criteria for minor depression, and we compared the demographic and clinical
      profiles of patients diagnosed with DDNOS who did and did not meet the criteria
      for minor depression METHODS: Three thousand four hundred psychiatric patients
      presenting to the Rhode Island Hospital outpatient practice were evaluated with
      semi-structured diagnostic interviews for DSM-IV Axis I and Axis II disorders and
      measures of psychosocial morbidity. RESULTS: More than 6% of the 3400 patients
      were diagnosed with DDNOS (n=227). Only a minority of the patients with DDNOS met
      the criteria for minor depression (39.8%). There was no difference between
      patients with "subthreshold" depression who did and did not meet the DSM-IV
      research criteria for minor depression in demographic characteristics, the
      prevalence of comorbid Axis I or Axis II disorders, history of major depressive
      disorder, and family history of depression. LIMITATIONS: The present study was
      conducted in a single outpatient practice in which the majority of patients were
      white, female, and had health insurance. Although the study was limited to a
      single site, a strength of the recruitment procedure was that the sample was not
      selected for participation in a treatment study, and exclusion and inclusion
      criteria did not reduce the representativeness of the patient groups. While we
      examined a number of validators, we did not systematically record the treatment
      the patients received and the outcome of treatment. CONCLUSIONS: Amongst
      psychiatric outpatients with clinically significant depression not meeting
      criteria for MDD or dysthymic disorder, there was little difference between
      patients who did and did not meet the DSM-IV research criteria for minor
      depressive disorder.

PMID- 23164464
TI  - Commentary on: Prognostic significance of 18-FDG PET/CT and EUS-defined tumour
      characteristics in patients with oesophageal cancer.

PMID- 23164465
TI  - HAX-1 is a nucleocytoplasmic shuttling protein with a possible role in mRNA
      processing.
AB  - HAX-1 is a multi-functional protein that is involved in the regulation of
      apoptosis, cell motility and calcium homeostasis. It is also reported to bind
      RNA: it associates with structural motifs present in the 3' untranslated regions
      of at least two transcripts, but the functional significance of this binding
      remains unknown. Although HAX-1 has been detected in various cellular
      compartments, it is predominantly cytoplasmic. Our detailed localization studies
      of HAX-1 isoforms revealed partial nuclear localization, the extent of which
      depends on the protein isoform. Further studies demonstrated that HAX-1 is in
      fact a nucleocytoplasmic shuttling protein, dependent on the exportin 1 nuclear
      export receptor. Systematic mutagenesis allowed identification of the two nuclear
      export signals in the HAX-1 sequence. HAX-1 nuclear accumulation was observed
      after inhibition of nuclear export by leptomycin B, but also after specific
      cellular stress. The biological role of HAX-1 nuclear localization and shuttling
      remains to be established, but the HAX-1 transcript-binding properties suggest
      that it may be connected to mRNA processing and surveillance. In this study, HAX
      1 status was shown to influence mRNA levels of DNA polymerase beta, one of the
      HAX-1 mRNA targets, although this effect becomes pronounced only after specific
      stress is applied. Moreover, HAX-1 tethering to the reporter transcript caused a
      significant decrease in its expression. Additionally, the HAX-1 co-localization
      with P-body markers, reported here, implies a role in mRNA processing. These
      results suggest that HAX-1 may be involved in the regulation of expression of
      bound transcripts, possibly as part of the stress response.

PMID- 23164466
TI  - Of babies and bathwater, and rabbits and rabbit holes: a plea for conflict
      prevention, not conflict promotion.
AB  - Dixon et al. overlook the fact that contact predicts not only favorable out-group
      attitudes/evaluations, but also cognitions, affect, and behavior. The weight of
      evidence supporting the benefits of intergroup contact cautions against throwing
      the (contact) baby out with the bathwater. The goal to "ignite struggles" in
      pursuit of social equality, we argue, incautiously risks hurling us down the
      proverbial rabbit hole.

PMID- 23164467
TI  - Seeking insights into the EPidemiology, treatment and Outcome of Childhood
      Arthritis through a multinational collaborative effort: Introduction of the EPOCA
      study.
AB  - The epidemiology of juvenile idiopathic arthritis (JIA) is variable worldwide.
      In particular, a wide disparity exists in the prevalence of the diverse disease
      subtypes across different geographic areas. The therapeutic approach to JIA is
      not standardized and no established and widely accepted guidelines are available.
      In the past decade, there have been important progresses in the management of the
      disease, but the availability of the novel and costly biologic medications is not
      uniform throughout the world. This issue may have significant impact on disease
      prognosis, with children living in poorer countries being at greater risk of
      accumulating disease- and treatment-related damage than children followed in
      Western pediatric rheumatology centers. The multinational study of the
      EPidemiology, treatment and Outcome of Childhood Arthritis (EPOCA study) is aimed
      to obtain information on the frequency of JIA subtypes in different geographic
      areas, the therapeutic approaches adopted by pediatric rheumatologists practicing
      in diverse countries or continents, and the disease and health status of children
      with JIA currently followed worldwide. Parent- and child-reported outcomes are
      meant to be recorded through the administration of a new multidimensional
      questionnaire, the Juvenile Arthritis Multidimensional Assessment Report (JAMAR).
      The first step of the study is based on the translation and cross-cultural
      adaptation of the questionnaire in the national language of each participating
      country. Each center is, then, asked to enroll a sample of consecutive JIA
      patients, who should undergo a retrospective assessment and a cross-sectional
      evaluation, including completion of the JAMAR, a standardized joint examination,
      and the assessment of articular and extra-articular damage. At the end of May
      2012, 124 centers in 55 countries have agreed to participate in the study. The
      JAMAR has been or is currently being translated in 38 national languages. The
      target patient sample is more than 10,000 JIA children worldwide.

PMID- 23164468
TI  - Two decades of fluorescence in situ hybridization in systematic and applied
      microbiology.

PMID- 23164469
TI  - Stent therapy for acute and chronic obstructions in extracardiac Fontan conduits.
AB  - We describe transcatheter therapy for early onset occlusion or stenoses of
      extracardiac conduits in three children who had undergone Fontan completion.
      Successful stent implantation was associated with complete resolution of
      symptoms.

PMID- 23164470
TI  - Quality of outpatient clinical notes: a stakeholder definition derived through
      qualitative research.
AB  - BACKGROUND: There are no empirically-grounded criteria or tools to define or
      benchmark the quality of outpatient clinical documentation. Outpatient clinical
      notes document care, communicate treatment plans and support patient safety,
      medical education, medico-legal investigations and reimbursement. Accurately
      describing and assessing quality of clinical documentation is a necessary
      improvement in an increasingly team-based healthcare delivery system. In this
      paper we describe the quality of outpatient clinical notes from the perspective
      of multiple stakeholders. METHODS: Using purposeful sampling for maximum
      diversity, we conducted focus groups and individual interviews with clinicians,
      nursing and ancillary staff, patients, and healthcare administrators at six
      federal health care facilities between 2009 and 2011. All sessions were audio
      recorded, transcribed and qualitatively analyzed using open, axial and selective
      coding. RESULTS: The 163 participants included 61 clinicians, 52 nurse/ancillary
      staff, 31 patients and 19 administrative staff. Three organizing themes emerged:
      1) characteristics of quality in clinical notes, 2) desired elements within the
      clinical notes and 3) system supports to improve the quality of clinical notes.
      We identified 11 codes to describe characteristics of clinical notes, 20 codes to
      describe desired elements in quality clinical notes and 11 codes to describe
      clinical system elements that support quality when writing clinical notes. While
      there was substantial overlap between the aspects of quality described by the
      four stakeholder groups, only clinicians and administrators identified ease of
      translation into billing codes as an important characteristic of a quality note.
      Only patients rated prioritization of their medical problems as an aspect of
      quality. Nurses included care and education delivered to the patient, information
      added by the patient, interdisciplinary information, and infection alerts as
      important content. CONCLUSIONS: Perspectives of these four stakeholder groups
      provide a comprehensive description of quality in outpatient clinical
      documentation. The resulting description of characteristics and content necessary
      for quality notes provides a research-based foundation for assessing the quality
      of clinical documentation in outpatient health care settings.

PMID- 23164471
TI  - SHBG in GDM maternal serum, placental tissues and umbilical cord serum expression
      changes and its significance.
AB  - AIMS: To compare the expression of sex hormone binding globulin (SHBG) in normal
      placental tissues and serum with placental tissues from patients with gestational
      diabetes mellitus (GDM) and to deduce the mechanism affecting placental SHBG in
      GDM. METHODS: Enzyme-linked immunosorbent assay (ELISA) method were used to
      detect SHBG levels changes in normal and GDM maternal serum, umbilical cord serum
      and placental. We measured SHBG mRNA and protein using reverse-transcription
      polymerase chain reaction, and Western blotting, respectively, in normal and GDM
      placental tissues. RESULTS: In maternal serum, compared with the control group,
      GDM group: glucose, insulin increased, SHBG decreased. In the placenta, compared
      with the control group, GDM group: SHBG, SHBG mRNA and SHBG protein decreased.
      There is no correlation between placenta SHBG and maternal serum SHBG
      respectively in control and GDM group, but in GDM group maternal serum insulin
      and placenta SHBG are linear correlation. CONCLUSIONS: GDM serum and placental
      SHBG levels are reduced, hyperinsulinemia may lead to a reduction of SHBG in
      circulating blood, but also damage the placenta cells which led to placental
      synthesis and secretion of SHBG decrease.

PMID- 23164472
TI  - [Chronic limping due to calcification in a subureteric Macroplastique((r))
      implant].
AB  - Endoscopic subureteric implantation of polydimethylsiloxane (Macroplastique((r)))
      to treat vesico-ureteric reflux is known to be safe and efficient, but long-term
      complications of this technique are often unknown. A 15-year-old patient was
      admitted to several hospital services with abdominal pain in the right lower
      quadrant and chronic limping. After multiple examinations, the diagnosis of renal
      colic due to the calcification of a Macroplastique((r)) implant was made.
      Calcification of an implant after endoscopic subureteral injection has already
      been described in the literature, but the clinical presentation of this
      complication is poorly reported, which can delay the diagnosis. The treatment can
      consist in an exeresis of the implanted material or even in ureteral
      reimplantation.

PMID- 23164473
TI  - [The new drunks].

PMID- 23164474
TI  - 2012: the year of appropriateness.

PMID- 23164475
TI  - Everolimus-eluting stents compared with paclitaxel-eluting stents for treatment
      of coronary in-stent restenoses.
AB  - BACKGROUND: Everolimus-eluting stent (EES) implantation was superior to
      paclitaxel-eluting stent (PES) implantation for treatment of de-novo coronary
      artery disease. We evaluated the outcome of EES compared with PES for treatment
      of restenosis in bare-metal and drug-eluting stents (DES). METHODS AND MATERIALS:
      In a prospective observational study patients with in-stent restenosis (ISR) were
      treated with EES (N=91) or PES (N=107). Dual antiplatelet therapy was given for 6
      months. Patients were scheduled for 6 months angiographic follow-up and 24 months
      clinical follow-up. Primary outcome measure was the occurrence of major adverse
      cardiac events (MACE) defined as a composite of cardiac death, any myocardial
      infarction and target lesion revascularization (TLR). RESULTS: Baseline data
      showed some differences between groups including frequency of DES restenosis,
      length of stented segment and reference vessel diameter. For EES versus PES
      occurrence of MACE (18.7% vs. 15.0%, p=0.48) and need for TLR did not differ
      (13.2% vs. 9.3%, p=0.39). In-stent late loss was similar with 0.20+/-0.39 mm for
      EES and 0.18+/-0.31mm for PES (p=0.34). Binary angiographic restenosis rate for
      the total segment was 18.0% and 16.7% (p=0.85), respectively. In multivariable
      analysis the stented length (p=0.014), minimal lumen diameter post stenting
      (p<0.01) and repeated restenosis (p<0.001) were risk factors for a higher late
      loss but not type of DES or presence of diabetes mellitus. CONCLUSIONS: In this
      observational registry treatment of DES and BMS restenosis with EES versus PES
      implantation resulted in similar clinical and angiographic outcome.

PMID- 23164476
TI  - Clinical presentation and predictors of target vessel revascularization after
      drug-eluting stent implantation.
AB  - BACKGROUND: Drug eluting stent (DES) failure including restenosis and stent
      thrombosis, or disease progression may result in target vessel revascularization
      (TVR) but the relative contribution of these mechanisms in the DES era is not
      well described. We sought to examine the predictors and presentations of patients
      with clinically driven TVR after DES. METHODS: Patients with all lesions treated
      with a DES in the Dynamic Registry from 2004 to 2006 were analyzed. Included were
      2691 patients with 3401 lesions. Patients with and without incident clinically
      driven TVR at 2years were compared according to baseline clinical, procedural,
      and angiographic characteristics and independent predictors of TVR and target
      lesion revascularization (TLR) were determined by multivariate analysis. RESULTS:
      By 2-years, TVR occurred in 7.2% of patients and TLR in 3.8%, with 71.6% and
      82.5% of repeat revascularization events occurring in the first year,
      respectively. The indication for first TVR was myocardial infarction in 18.6%
      (n=34), unstable angina in 42.6% (n=78), stable coronary disease in 25.7% (n=47)
      and other/unknown in 13.1% (n=24). Disease progression was responsible for 47% of
      TVR. Among patients with TLR, restenosis was the mechanism in 86.6% and stent
      thrombosis in 13.4%. Independent predictors of TVR included younger age,
      diabetes, attempted graft lesion, lesion length >30mm and prior lesion
      intervention. Independent predictors of TVR and TLR were similar. CONCLUSION: The
      incidence of clinically driven TVR is low in patients treated with DES and nearly
      half is attributable to disease progression, which along with the low rate of in
      stent restenosis explains why the mode of presentation is often an acute coronary
      syndrome.

PMID- 23164477
TI  - Safety and efficacy of the cobalt chromium PRO-Kinetik coronary stent system:
      results of the MULTIBENE study.
AB  - BACKGROUND: The aim of this MULTIBENE study was to evaluate the safety and
      efficacy of the silicon carbide coated cobalt chromium PRO-Kinetik coronary stent
      system in patients with single de novo coronary lesions. METHODS AND MATERIALS:
      This prospective international multicenter study included 202 patients at 10
      European sites. Analysis was performed on the per protocol population of 197
      patients. Patients were followed until 12 months, a subset of patients (n=72)
      underwent additional coronary angiography at 6 months. Primary endpoint was 6
      months rate of target vessel failure (TVF), defined as a composite of cardiac
      death, myocardial infarction and target vessel revascularization (TVR). RESULTS:
      At 6 months, rate of TVF was 10.9% and rate of major adverse cardiac events, a
      composite of cardiac death, MI, target lesion revascularization (TLR) and
      coronary artery bypass graft, was 11.4%, both being mainly attributed to TVR
      respective TLR. No cardiac death or stent thrombosis occurred. In-segment late
      lumen loss was 0.66+/-0.61mm and binary restenosis was 20.8%, as determined by
      core laboratory in the angiographic subgroup. CONCLUSION: Based on these data,
      the PRO-Kinetik coronary stent system was found to be safe and effective.

PMID- 23164479
TI  - Neural markers of negative symptom outcomes in distributed working memory brain
      activity of antipsychotic-naive schizophrenia patients.
AB  - Since working memory deficits in schizophrenia have been linked to negative
      symptoms, we tested whether features of the one could predict the treatment
      outcome in the other. Specifically, we hypothesized that working memory-related
      functional connectivity at pre-treatment can predict improvement of negative
      symptoms in antipsychotic-treated patients. Fourteen antipsychotic-naive patients
      with first-episode schizophrenia were clinically assessed before and after 7
      months of quetiapine monotherapy. At baseline, patients underwent functional
      magnetic resonance imaging while performing a verbal n-back task. Spatial
      independent component analysis identified task-modulated brain networks. A linear
      support vector machine was trained with these components to discriminate six
      patients who showed improvement in negative symptoms from eight non-improvers.
      Classification accuracy and significance was estimated by leave-one-out cross
      validation and permutation tests, respectively. Two frontoparietal and one
      default mode network components predicted negative symptom improvement with a
      classification accuracy of 79% (p = 0.003). Discriminating features were found in
      the frontoparietal networks but not the default mode network. These preliminary
      data suggest that functional patterns at baseline can predict negative symptom
      treatment-response in schizophrenia. This information may be used to stratify
      patients into subgroups thereby facilitating personalized treatment.

PMID- 23164480
TI  - Islet-cell dysfunction induced by glucocorticoid treatment: potential role for
      altered sympathovagal balance?
AB  - AIM: Glucocorticoids impair glucose tolerance by inducing insulin resistance. We
      investigated the dose-dependent effects of glucocorticoid treatment on islet-cell
      function in healthy males and studied the role of the autonomic nervous system.
      DESIGN AND METHODS: A randomized, placebo-controlled, double-blind, dose-response
      intervention study was conducted in 32 healthy males (age: 21+/-2years; BMI:
      21.9+/-1.7kg/m(2)). Participants were allocated to prednisolone 7.5mg once daily
      (n=12), prednisolone 30mg once daily (n=12), or placebo (n=8) for two weeks. Beta
      cell function was measured by hyperglycemic clamp with arginine stimulation,
      glucagon levels were measured following a standardized meal test. RESULTS: We
      found that prednisolone treatment dose-dependently reduced C-peptide secretion
      following arginine stimulation on top of hyperglycemia (ASI-iAUCCP): -2.8 (
      5.2;0.2) and -3.1 (-8.8; -1.0) nmolL(-1)min(-1) for prednisolone 7.5mg and
      prednisolone 30mg, respectively (P=0.035 vs. placebo). Fasting glucagon levels
      increased dose-dependently (vs. placebo; P=0.001), whereas postprandial glucagon
      levels were only increased by prednisolone 30mg. Changes in parasympathetic
      activity related with changes in fasting glucose levels (r=-0.407; P=0.03) and
      showed a trend towards correlation with fasting glucagon concentrations (r=
      0.337; P=0.07). The change in sympathovagal balance was inversely related to ASI
      iAUCCP (r=-0.365; P=0.05). CONCLUSION: We conclude that in addition to inducing
      insulin resistance, prednisolone treatment dose-dependently impaired islet-cell
      function. Altered sympathovagal balance may be related to these effects.

PMID- 23164481
TI  - Sensory and sensorimotor gating in children with multiple complex developmental
      disorders (MCDD) and autism.
AB  - Multiple Complex Developmental Disorder (MCDD) is a well-defined and validated
      behavioral subtype of autism with a proposed elevated risk of developing a
      schizophrenic spectrum disorder. The current study investigated whether children
      with MCDD show the same deficits in sensory gating that are commonly reported in
      schizophrenia, or whether they are indistinguishable from children with autism in
      this respect. P50 suppression and prepulse inhibition (PPI) of the startle reflex
      were assessed in children with MCDD (n=14) or autism (n=13), and healthy controls
      (n=12), matched on age and IQ. All subjects showed high levels of PPI and P50
      suppression. However, no group differences were found. No abnormalities in
      sensory filtering could be detected in children with autism or MCDD. Since
      sensory gating deficits are commonly regarded as possible endophenotypic markers
      for schizophrenia, the current results do not support a high level of similarity
      between schizophrenia and MCDD.

PMID- 23164482
TI  - Early hospitalization of patients with TIA: a prospective, population-based
      study.
AB  - BACKGROUND: The German Stroke Society (GSS) recommends early hospitalization of
      patients with transient ischemic attack (TIA) regardless of ABCD(2) score. This
      population-based study determined the rate of stroke during hospitalization and
      within 3 months after discharge, as well as the rates of mortality and
      readmission during the 3 months after discharge in patients with TIA. METHODS:
      During a 36-month period (starting November 2007), 2200 consecutive patients
      (mean age, 70.6 +/- 12.8 years; 49% women) with TIA from 15 hospitals in the
      Federal State of Schleswig-Holstein (1 of the 16 states in Germany) were
      prospectively evaluated during hospitalization and a follow-up time of 3 months
      after discharge. The primary outcomes were stroke during hospitalization and 3
      months after discharge, as well as readmission and mortality at 3 months. Odds
      ratios (ORs) were calculated by the adjusted logistic regression analysis.
      RESULTS: Of 2200 patients (median time of admission, 6 hours from symptom onset),
      24 patients (1.1%; 95% confidence interval [CI], 0.7%-1.5%) experienced a stroke
      during hospitalization (mean, 6 days), and of 1335 patients, 38 (2.8%; 95% CI,
      2.1%-3.8%) experienced a stroke during the 3 months after discharge. Stroke
      during hospitalization was independently correlated with male sex (OR, 3.5) and
      acute brain infarction detected by brain imaging (OR, 2.6), whereas stroke within
      3 months correlated with age greater than 65 years (OR, 3.0). The readmission
      rate (11.1%; 95% CI, 9.3%-12.7%) was increased in patients who had had previous
      stroke (OR, 1.7) but decreased in patients who were discharged with statin
      medication (OR, 0.6). The 3-month mortality (1.4%; 95% CI, 0.9%-1.9%) was
      independently correlated with unilateral weakness (OR, 2.6) and atrial
      fibrillation (AF) (OR, 2.6). CONCLUSIONS: These findings may help clinicians to
      estimate the TIA prognosis in patients who were hospitalized early with TIA.

PMID- 23164483
TI  - Early neurologic improvement based on the National Institutes of Health Stroke
      Scale score predicts favorable outcome within 30 minutes after undergoing
      intravenous recombinant tissue plasminogen activator therapy.
AB  - BACKGROUND: The aim of the present study was to evaluate whether early neurologic
      improvement (within 30 minutes), as measured using the National Institutes of
      Health Stroke Scale (NIHSS) score, predicts favorable outcome at 90 days.
      METHODS: Consecutive acute ischemic stroke patients treated with intravenous
      recombinant tissue plasminogen activator (i.v. rt-PA) within 3 hours poststroke
      between March 2006 and September 2011 were analyzed retrospectively. The
      association between early neurologic improvement based on the NIHSS score (an
      improvement of >=3 points at 15 minutes and >=5 points at 30 minutes) and
      favorable outcome at 90 days was examined. A favorable outcome was defined as a
      modified Rankin scale (mRS) score of 0 or 1 at 90 days after treatment. RESULTS:
      On examination of the time course of the NIHSS score in patients with an
      improvement of >=8 points or a score of 0 on the NIHSS after 24 hours, the NIHSS
      score improved significantly from 15 minutes after i.v. rt-PA treatment (P =
      .042) and at 30 minutes (P = .014). On logistic regression analysis, an
      improvement of >=3 NIHSS points at 15 minutes (odds ratio [OR] 6.78; 95%
      confidence interval [CI] 1.72-26.70; P = .006) and an improvement of >=5 NIHSS
      points at 30 minutes (OR 4.83; 95% CI 1.05-22.28; P = .043) were associated with
      a favorable outcome. CONCLUSIONS: An improvement of at least 3 points in the
      NIHSS score at 15 minutes or of at least 5 points at 30 minutes appears to be a
      predictor of favorable outcome and helps to identify patients who will not
      respond to rt-PA therapy.

PMID- 23164484
TI  - Inflammation in COPD: implications for management.
AB  - Chronic obstructive pulmonary disease (COPD) is recognized by the Global
      Initiative for Chronic Obstructive Lung Disease guidelines as an inflammatory
      disease state, and treatment rationales are provided accordingly. However, not
      all physicians follow or are even aware of these guidelines. Research has shown
      that COPD inflammation involves multiple inflammatory cells and mediators and the
      underlying pathology differs from asthma inflammation. For these reasons,
      therapeutic agents that are effective in asthma patients may not be optimal in
      COPD patients. COPD exacerbations are intensified inflammatory events compared
      with stable COPD. The clinical and systemic consequences believed to result from
      the chronic inflammation observed in COPD suggest that inflammation intensity is
      a key factor in COPD and exacerbation severity and frequency. Although inhaled
      corticosteroids are commonly used and are essential in asthma management, their
      efficacy in COPD is limited, with only a modest effect at reducing exacerbations.
      The importance of inflammation in COPD needs to be better understood by
      clinicians, and the differences in inflammation in COPD versus asthma should be
      considered carefully to optimize the use of anti-inflammatory agents.

PMID- 23164485
TI  - Introduction of high-sensitivity troponin assays: impact on myocardial infarction
      incidence and prognosis.
AB  - OBJECTIVE: The study objective was to compare the incidence and prognosis of
      acute myocardial infarction when using high-sensitivity cardiac troponin assays
      instead of a standard cardiac troponin assay for the diagnosis of acute
      myocardial infarction. METHODS: In a prospective international multicenter study,
      we enrolled 1124 consecutive patients presenting with suspected acute myocardial
      infarction. Final diagnoses were adjudicated by 2 independent cardiologists 2
      times using all available clinical information: first using standard cardiac
      troponin levels and second using high-sensitivity cardiac troponin T levels for
      adjudication. Patients were followed up for a mean of 19+/-9 months. RESULTS: The
      use of high-sensitivity cardiac troponin T instead of standard cardiac troponin
      resulted in an increase in the incidence of acute myocardial infarction from 18%
      to 22% (242 vs 198 patients), a relative increase of 22%. Of the 44 additional
      acute myocardial infarctions, 35 were type 1 acute myocardial infarctions and 9
      were type 2 acute myocardial infarctions. This was accompanied by a reciprocal
      decrease in the incidence of unstable angina (unstable angina, 11% vs 13%). The
      most pronounced increase was observed in patients adjudicated with cardiac
      symptoms of origin other than coronary artery disease with cardiomyocyte damage
      (83 vs 31 patients, relative increase of 268%). Cumulative 30-month mortality
      rates were 4.8% in patients without acute myocardial infarction, 16.4% in
      patients with a small acute myocardial infarction detected only by high
      sensitivity cardiac troponin T but not standard cardiac troponin, and 23.9% in
      patients with a moderate/large acute myocardial infarction according to standard
      cardiac troponin assays and high-sensitivity cardiac troponin T (P<.001).
      CONCLUSIONS: The introduction of high-sensitivity cardiac troponin assays leads
      to only a modest increase in the incidence of acute myocardial infarction. The
      novel sensitive assays identify an additional high-risk group of patients with
      increased mortality, therefore appropriately classified with acute myocardial
      infarction (Advantageous Predictors of Acute Coronary Syndromes Evaluation;
      NCT00470587).

PMID- 23164486
TI  - Bleeding risk after invasive procedures in aspirin/NSAID users: polypectomy study
      in veterans.
AB  - BACKGROUND: Aspirin, by virtue of inhibition of platelet hemostatic function, is
      withheld before many invasive procedures because of the bleeding risk. American
      Society of Gastrointestinal Endoscopy guidelines acknowledge the paucity of "high
      quality data" to make recommendations regarding the use of aspirin (ASA) and
      nonsteroidal anti-inflammatory drugs (NSAIDs) before endoscopic procedures. Yet
      the majority of endoscopists hold ASA/NSAIDs before polypectomy. METHODS: This
      single-center, retrospective, cohort study was conducted at Veterans Affairs
      Medical Center, Syracuse, NY. The objectives were to assess the postpolypectomy
      bleeding risk in ASA/NSAID users in a large cohort of veterans undergoing
      colonoscopic polypectomy and to identify risk factors associated with
      postpolypectomy bleeding. All patients undergoing polypectomy between January
      2002 and October 2007 were eligible. Patients on anticoagulants/other
      antiplatelet agents were excluded. Patients were selected randomly by cluster
      sampling techniques. Electronic medical and pharmacy records were reviewed for
      patient demographics, polypectomy techniques, and postpolypectomy bleeding rates.
      Univariate analysis was performed between patients on ASA and NSAIDs (group A)
      versus those not on ASA or NSAIDs (group B). Multiple regression analysis was
      performed to identify independent risk factors associated with postpolypectomy
      bleeding. RESULTS: Five hundred two (43%) of 1174 patients (mean age 66 years,
      92% white) were on ASA or NSAIDs, or both. There was no significant difference
      between postpolypectomy bleeding rates among the 2 groups (3.2% vs 3.0%). Age,
      sex, polyp characteristics, and polypectomy techniques were comparable between
      groups A and B. In multiple logistic regression analysis, ASA or NSAID use was
      not a significant risk factor for postpolypectomy bleeding. Number of polyps
      removed per patient was the only risk factor significantly associated with
      postpolypectomy bleeding (P <.01, odds ratio 1.3, 95% confidence interval, 1.18
      1.43). CONCLUSIONS: In this large study, use of ASA or NSAIDs did not increase
      the risk of postpolypectomy bleeding. Cessation of ASA/NSAIDs before
      colonoscopy/polypectomy is therefore unnecessary.

PMID- 23164487
TI  - The role of aspirin in primary prevention of vascular events.

PMID- 23164488
TI  - Acid base: back to the basics of Henderson-Hasselbalch.

PMID- 23164489
TI  - The bias of a 'clean' comparison group.

PMID- 23164491
TI  - Tackling thermosensation with multidimensional phenotyping.
AB  - Most if not all animals sense temperature using specialized thermosensory
      neurons. Genetic studies in simple organisms have been used to identify gene
      products required for detecting temperature changes or for mediating the effects
      of temperature on behaviour. A recent study has used automated imaging and
      multidimensional phenotyping to characterize behavioural responses to aversive
      temperature changes and to identify mutants with specific defects in these
      processes.

PMID- 23164492
TI  - The politics of moving beyond prejudice.
AB  - Dixon et al. have highlighted the importance of a political conceptualisation of
      intergroup relations that challenges individualising models of social change. As
      important as this paper is for the development of critical debates in psychology,
      we can detect at least three issues that warrant further discussion: (a) the
      cultural and historical conditions of structural inequality and its perception,
      (b) the marginalisation of post-colonial works on collective mobilisation, and
      (c) acknowledging the complex perspectives and politics of those targeted by
      prejudice.

PMID- 23164493
TI  - Four-year experience with outpatient laparoscopic adjustable gastric banding.
AB  - BACKGROUND: Outpatient laparoscopic procedures have been performed in various
      fields of surgery, and laparoscopic gastric banding is no exception. We present
      our series of outpatient laparoscopic adjustable gastric banding procedures
      performed at 2 centers. METHODS: A total of 348 patients were retrospectively
      analyzed. All patients met the National Institutes of Health criteria for
      bariatric surgery. Additionally, to be included in an outpatient surgery
      procedure, patients had to meet 4 other criteria: body mass index<55, American
      Society of Anesthesiologists class <= 3, no extensive abdominal surgical history
      (in the upper gastrointestinal tract), and no untreated sleep apnea. RESULTS:
      There were 282 women and 66 men, with a mean age of 41.3 years. The mean
      preoperative weight and BMI were 266.7 pounds and 43.1 kg/m(2), respectively. The
      median operative time was 70 minutes, and the median blood loss was 5 mL. The
      median length of stay was .3 day (range .1-.4). Fifty-seven patients underwent
      additional associated procedures. During follow-up, 20 patients required a
      reoperation. Two patients required admission to the hospital. There was no
      perioperative or postoperative mortality. Before discharge, all patients
      underwent an upper gastrointestinal swallow. CONCLUSION: Outpatient laparoscopic
      adjustable gastric banding is a well-tolerated, cost-effective bariatric
      procedure for patients who meet the inclusion criteria.

PMID- 23164494
TI  - Determinants of physical activity in young adults with tetralogy of Fallot.
AB  - BACKGROUND: Although sports participation is allowed to most adult patients with
      corrected tetralogy of Fallot, a reduced exercise tolerance and reduced perceived
      physical functioning is often present in these patients. We aimed to investigate
      daily physical activity in adults with tetralogy of Fallot and to investigate the
      underlying determinants of physical activity in daily life. METHODS: We studied
      73 patients with tetralogy of Fallot (53 male; mean age 27.3 +/- 7.9 years) who
      underwent echocardiography and cardiopulmonary exercise testing, and who
      completed questionnaires about physical activity and perceived health status. All
      variables were compared with data from a general population. Relationships were
      studied by Pearson or Spearman correlation coefficients with correction for
      multiple testing. RESULTS: Patients were significantly less active compared with
      the general population (p > 0.05), 55% of all patients were sedentary, 27% had an
      active or moderately active lifestyle, and 18% of the group had a vigorously
      active lifestyle. Peak oxygen uptake (71 +/- 16%; p < 0.0001) was significantly
      reduced and related to reduced physical activity levels (r = 0.229; p = 0.017)
      and perceived physical functioning (r = 0.361; p = 0.002). CONCLUSIONS: Adult
      patients with tetralogy of Fallot have a sedentary lifestyle and are less active
      than the general population. Inactivity significantly contributes to reduced
      exercise capacity, in addition to the impairment based on the cardiac condition.
      Moreover, reduced exercise capacity and the intensity of sports performed in
      daily life are related to perceived physical functioning. Individual patient
      counselling on physical activity might be a low-cost, high-benefit measure to be
      taken in this patient population.

PMID- 23164495
TI  - Functional network connectivity in the behavioral variant of frontotemporal
      dementia.
AB  - INTRODUCTION: The aim of this study was to investigate, using resting state (RS)
      functional magnetic resonance imaging (fMRI), the functional connectivity within
      and among brain networks in patients with the behavioral variant of
      frontotemporal dementia (bvFTD), compared with healthy controls and patients with
      probable Alzheimer's disease (pAD). METHODS: Twelve bvFTD patients were compared
      with 30 controls and 18 pAD patients. Functional connectivity within the
      salience, default mode (DMN), executive (EXN), attention/working memory (ATT/WM),
      and dorsal attentional networks was assessed using independent component
      analysis. The temporal associations among RS networks (RSNs) were explored using
      the functional network connectivity toolbox. RESULTS: A decreased dorsal salience
      network (DSN) connectivity, mainly involving the anterior cingulum, was observed
      in bvFTD versus controls and pAD. BvFTD was also characterized by a decreased
      ventral salience network connectivity in the basal ganglia, and divergent
      connectivity effects versus controls in the dorsolateral prefrontal cortex
      (decreased) and precuneus (enhanced) within the right ATT/WM network. The dorsal
      attentional network had a decreased connectivity with the DMN and EXN in bvFTD
      versus controls, and a decreased connectivity with the DSN versus pAD.
      CONCLUSIONS: RSN functional abnormalities occur in bvFTD, involving not only the
      salience network, but also the DMN and fronto-parietal network associated with
      ATT and WM modulation. The pattern of functional changes differs from that seen
      in pAD. The altered interactions among RSN observed in bvFTD and pAD may provide
      a new venue to explore the functional correlates of cognitive abnormalities in
      neurodegenerative and psychiatric disorders.

PMID- 23164496
TI  - Rickettsia africae in Hyalomma dromedarii ticks from sub-Saharan Algeria.
AB  - Spotted fever group (SFG) rickettsioses are caused by obligate, intracellular
      Gram-negative bacteria of the genus Rickettsia. In recent years, several species
      and subspecies of rickettsias have been identified as emerging pathogens
      throughout the world, including sub-Saharan Africa. We report here the detection
      of Rickettsia africae, the agent responsible for African tick-bite fever, by
      amplification of fragments of gltA and ompA genes and multi-spacer typing from
      Hyalomma dromedarii ticks collected from the camel Camelus dromedarius in the
      Adrar and Bechar region (sub-Saharan Algeria). To date, R. africae has been
      associated mainly with Amblyomma spp. The role of H. dromedarii in the
      epidemiology of R. africae requires further investigation.

PMID- 23164497
TI  - MR elastography of the head and neck: driver design and initial results.
AB  - PURPOSE: The purpose was to describe the design and fabrication of a driver
      suitable for magnetic resonance elastography (MRE) of the head and neck and to
      assess its performance in evaluating human parotid gland, lymph nodes and thyroid
      at 3.0 T. MATERIALS AND METHODS: A head and neck driver was fabricated using a
      commercial transducer, headrest mould and piston extension. Driver performance
      was tested using a motion-sensitized spin-echo MRE pulse sequence. Six healthy
      volunteers and three patients (two metastatic nodes and one papillary carcinoma)
      were evaluated using MRE. Viscoelastic maps were computed to obtain storage
      modulus (G') and loss modulus (G") of the normal parotid and thyroid, metastatic
      node and thyroid cancer. Reproducibility was assessed by coefficient of
      variation. RESULTS: All subjects completed MRE examination without discomfort.
      Initial G' and G" values were as follows: normal parotid gland, 1.12 kPa and 0.48
      kPa; thyroid, 0.58 kPa and 0.42 kPa; metastatic node, 0.66 kPa and 0.58 kPa; and
      thyroid cancer, 0.17 kPa and 0.28 kPa. Based on parotid data, the coefficient of
      variation for G' and G" was 4.7% and 9.8%. CONCLUSION: A new MRE driver for head
      and neck was successfully implemented, and our initial results suggested the
      device was suitable for the mechanical assessment of tissues in the head and
      neck.

PMID- 23164498
TI  - Effect of estrogen on rat placental development depending on gestation stage.
AB  - We examined the sequential histopathological changes in the placenta from rats
      exposed to estrogen. 17 beta-estrogiol-3-benzoate was intraperitoneally
      administered at 100 MUg/animal/day during GD 6 to GD 8 (GD6-8 treated group), GD
      9 to GD 11 (GD9-11 treated group) and GD 12 to GD 14 (GD12-14 treated group), and
      the placentas were sampled on GDs 11, 13, 15, 17, and 21. Fetal mortality rates
      were increased up to approximately 50% in the GD6-8 and 9-11 treated groups, but
      there was no change of fetal weight on GD 21. An increase in placental weight and
      a reduction in fetal/placental weight ratio were detected during GD 17 to GD 21
      in the GD6-8 treated group. Histopathologically, hypoplasia of metrial gland was
      detected with defective development of spiral arteries in the GD6-8 and GD9-11
      treated groups. A decrease in the thickness of metrial gland was observed from GD
      11 onwards in the GD6-8 treated group and from GD 13 onwards in the GD9-11
      treated group. The endovascular trophoblasts invaded into the spiral arteries in
      the deep part of metrial gland in these treated groups. The number of phospho
      histone H3 positive cells was decreased on GD 11 or GD 13 in these groups. In the
      decidua basalis, transitory necrosis was observed with hemorrhage on GD 13 in the
      GD6-8 and GD9-11 treated groups. In the labyrinth zone, cystic dilatation of the
      sinusoid was observed with congestion in the GD6-8 treated group, resulting in an
      increased placental weight. Therefore, we consider that estrogen inhibits the
      proliferation of decidualized endometrial stromal cells in the metrial gland, and
      leads to metrial gland hypoplasia with less development of the spiral arteries.
      The reduced utero-placental blood flow is supposed to be one of the important
      factors for poor reproductive performance.

PMID- 23164499
TI  - Child abuse: multiple foreign bodies in gastrointestinal tract.
AB  - The incidents of foreign body ingestion in infants and children are usually
      viewed as accidents, but these events may be a form of child abuse. We are
      reporting a case of child abuse who presented with multiple foreign bodies in the
      gastrointestinal tract. Physicians are required to report abuse when they have
      reason to believe or to suspect that it occurred. The purpose of reporting is not
      punishment of the perpetrator - it is the protection of the child. It is
      certainly in the best interest of the child, because child abuse is a recurrent
      and usually escalating problem that exposes the child to substantial risk.

PMID- 23164500
TI  - Bilateral objective tinnitus in an infant with tuberous sclerosis.
AB  - This is the first report of objective tinnitus presenting as audible spontaneous
      otoacoustic emission in a patient with tuberous sclerosis. The tinnitus was loud,
      continuous, and high pitched: 7757.8 and 6257.8 Hz. The auditory system may be
      dysfunctional in patients with tuberous sclerosis. Possible causes of tinnitus in
      these patients are abnormal myelination and dysfunctional axons and neurons
      associated with tuberous sclerosis. A disturbance of the outer hair cells or the
      MOC efferent fibers innervating the outer hair cells is considered to be the
      source of the loud spontaneous otoacoustic emission.

PMID- 23164501
TI  - Paralyzed neonatal larynx in adduction. Case series, systematic review and
      analysis.
AB  - OBJECTIVE: Bilateral vocal cord abductor paralysis (BVCAbP) is considered a rare
      cause of stridor in the newborn. The goal of this work is to present a case
      series and to review systematically the literature on bilateral vocal cord
      abductor paralysis in the newborn to better characterize the current knowledge on
      this entity. METHODS: We performed a systematic literature review with Medline
      (1950-2011). The authors screened all cases of BVCAbP reported and selected those
      affecting newborns. RESULTS: Out of the 129 articles screened, 16 were included.
      A total of 69 cases could be retrieved and analyzed. Associated co-morbidities
      were found in 54% of the patients, most notably malformative conditions
      (intracranial or other), or a positive perinatal history (trauma/asphyxia,
      prematurity). Tracheostomy placement was required in 59% of children, and of
      these 44% were successfully decannulated. In terms of functional outcome full
      recovery or improvement were seen in 61% of patients. Major underlying co
      morbidities affected negatively the functional outcome (p=.004), but not the need
      for tracheostomy (p=.604) or the decannulation success rate (p=.063). CONCLUSION:
      BVCAbP in the newborn is a serious cause of airway obstruction. It can be seen
      either in a context of multisystem anomalies or as an isolated finding. Newborns
      with major co-morbidities affecting their normal development are more likely to
      have poor functional outcomes and to remain tracheostomy-dependant.

PMID- 23164502
TI  - Measurements of normal nasal airway assessed by 3-dimensional computed tomography
      in Chinese children and adolescents.
AB  - OBJECTIVE: To establish normative data of nasal airway dimensions in Chinese
      children and adolescents by age and sex. METHODS: CT images of 281 Chinese
      children and adolescents (140 girls and 141 boys) aged from 6 to 18 years (yr)
      were selected among the patients who visited in Shanghai Ninth People's Hospital
      from September 2009 to August 2010. Subjects were divided into four age groups as
      group 1 (6-9 yr), group 2 (10-12 yr), group 3 (13-15 yr), and group 4 (16-18 yr).
      Child was defined as 6-12 yr, and adolescent as 13-18 yr. Nasal parameters were
      as follow: nasal volume (NV), length of nasal airway (NL), minimal cross-section
      area (CSA 1) and its location (D 1), inferior turbinate head's location (D 2) and
      its airway cross-section area (CSA 2), and cross-sectional area of choanal (CSA
      3). RESULTS: There was no significant sex dimorphism in nasal parameters in
      children (group 1 and group 2). In adolescents, male's nasal dimension were
      larger than female's. CSA 1, D 1, CSA 2, CSA 3, NL and NV correlated with age in
      male and female respectively. CONCLUSIONS: Volume, length and cross-section area
      of nasal airway were correlated with age in Chinese children and adolescents aged
      from 6 to 18 yr. In children, nasal conformations of male and female are similar.
      In adolescents, sex dimorphisms in nasal parameters were significant.

PMID- 23164503
TI  - Aberrant DNA methylation of imprinted loci in human in vitro matured oocytes
      after long agonist stimulation.
AB  - OBJECTIVE: To evaluate the epigenetic risk linked to assisted reproductive
      technology at oocyte level by analyzing methylation status of imprinted H19, PEG1
      and KvDMR1 in human MII oocytes rescue-matured from MI/GV oocytes after long
      agonist stimulation. STUDY DESIGN: 580 MI/GV oocytes from 275 patients receiving
      an ICSI procedure were additionally cultured for 24h, and 221 rescue-matured MII
      oocytes were obtained. Pyrosequencing with confirmatory routine bisulfite
      sequencing were used to determine the methylation status of H19 DMR in 35
      oocytes, PEG1 DMR in 47 oocytes, and KvDMR1 in 34 oocytes. RESULTS: Abnormal
      methylation status were found in 22.9% oocytes at H19 DMR, 17.0% oocytes at PEG1
      DMR and 8.8% oocytes at KvDMR1. CONCLUSION: We hypothesize that the use of MII
      rescue oocytes may increase the risk of imprinting defects because they might not
      have completed full imprinting programme.

PMID- 23164504
TI  - Transobturator vaginal tape for the treatment of stress urinary incontinence in
      elderly women without concomitant pelvic organ prolapse: is it effective and
      safe?
AB  - OBJECTIVE: To evaluate the efficacy and safety of the transobturator approach
      (TVT-O) for the surgical management of stress urinary incontinence (SUI) in older
      women. STUDY DESIGN: Between 2007 and 2010, all consecutive women with SUI
      undergoing an isolated TVT-O procedure were prospectively enrolled in this study.
      Patients were divided into two groups by age: older women (>= 70 years old) were
      included in group 1, while younger women (< 70 years old) in group 2. Intra- and
      post-operative outcomes were compared between the groups. RESULTS: During the
      study period 181 women met the inclusion criteria and were included for final
      analysis. Among these women, 60 (33.1%) and 121 (66.9%) were included in groups 1
      and 2 respectively. After a median follow-up of 26 (IQR 15-41) months for the
      younger and 25 (IQR 18-40) months for older patients (p>0.99), no differences
      were observed between the two groups in terms of cure rate (92.5% vs. 88.3%;
      p=0.40). No differences were observed in terms of voiding dysfunction, vaginal
      erosion and persistent groin pain, or in terms of onset of de novo overactive
      bladder (9.0% vs. 13.3%; p=0.44). CONCLUSIONS: TVT-O appears to be a safe and
      effective procedure for the management of stress urinary incontinence also in
      elderly population.

PMID- 23164505
TI  - Behavioural and neuroplastic properties of chronic lurasidone treatment in
      serotonin transporter knockout rats.
AB  - Second-generation antipsychotics (SGA) are multi-target agents widely used for
      the treatment of schizophrenia and bipolar disorder that also hold potential for
      the treatment of impaired emotional control, thanks to their diverse receptor
      profiles as well as their potential in modulating neuroadaptive changes in key
      brain regions. The aim of this study was thus to establish the ability of
      lurasidone, a novel SGA characterized by a multi-receptor signature, to modulate
      behavioural and molecular defects associated with a genetic model of impaired
      emotional control, namely serotonin transporter knockout (SERT KO) rats. At
      behavioural level, we found that chronic lurasidone treatment significantly
      increased fear extinction in SERT KO rats, but not in wild-type control animals.
      Moreover, at molecular level, lurasidone was able to normalize the reduced
      expression of the neurotrophin brain-derived neurotrophic factor in the
      prefrontal cortex of SERT KO rats, an effect that occurred through the regulation
      of specific neurotrophin transcripts (primarily exon VI). Furthermore, chronic
      lurasidone treatment was also able to restore the reduced expression of different
      GABAergic markers that is present in these animals. Our results show that
      lurasidone can improve emotional control in SERT KO rats, with a primary impact
      on the prefrontal cortex. The adaptive changes set in motion by repeated
      treatment with lurasidone may in fact contribute to the amelioration of
      functional capacities, closely associated with neuronal plasticity, which are
      deteriorated in patients with schizophrenia, bipolar disease and major
      depression.

PMID- 23164506
TI  - Cardiac arrest and neuromuscular blockade reversal agents in the transplanted
      heart.

PMID- 23164507
TI  - Interleukin-1 beta-induced up-regulation of opioid receptors in the untreated and
      morphine-desensitized U87 MG human astrocytoma cells.
AB  - BACKGROUND: Interleukin-1beta (IL-1beta) is a pro-inflammatory cytokine that can
      be produced in the central nervous system during inflammatory conditions. We have
      previously shown that IL-1beta expression is altered in the rat brain during a
      morphine tolerant state, indicating that this cytokine may serve as a convergent
      point between the immune challenge and opiate mediated biological pathways. We
      hypothesized that IL-1beta up-regulates opioid receptors in human astrocytes in
      both untreated and morphine-desensitized states. METHODS: To test this
      hypothesis, we compared the basal expression of the mu (MOR), delta (DOR), and
      kappa (KOR) opioid receptors in the human U87 MG astrocytic cell line to SH-SY5Y
      neuronal and HL-60 immune cells using absolute quantitative real time RT-PCR (AQ
      rt-RT-PCR). To demonstrate that IL-1beta induced up-regulation of the MOR, DOR
      and KOR, U87 MG cells (2 x 105 cells/well) were treated with IL-1beta (20 ng/mL
      or 40 ng/mL), followed by co-treatment with interleukin-1 receptor antagonist
      protein (IL-1RAP) (400 ng/mL or 400 ng/mL). The above experiment was repeated in
      the cells desensitized with morphine, where U87 MG cells were pre-treated with
      100 nM morphine. The functionality of the MOR in U87 MG cells was then
      demonstrated using morphine inhibition of forksolin-induced intracellular cAMP,
      as determined by radioimmunoassay. RESULTS: U87 MG cells treated with IL-1beta
      for 12 h showed a significant up-regulation of MOR and KOR. DOR expression was
      also elevated, although not significantly. Treatment with IL-1beta also showed a
      significant up-regulation of the MOR in U87 MG cells desensitized with morphine.
      Co-treatment with IL-1beta and interleukin-1 receptor antagonist protein (IL
      1RAP) resulted in a significant decrease in IL-1beta-mediated MOR up-regulation.
      CONCLUSION: Our results indicate that the pro-inflammatory cytokine, IL-1beta,
      affects opiate-dependent pathways by up-regulating the expression of the MOR in
      both untreated and morphine-desensitized U87 MG.

PMID- 23164508
TI  - Immunofluorescence protects RNA signals in simultaneous RNA-DNA FISH.
AB  - Cell research often requires combinational detection of RNA and DNA by
      fluorescence in situ hybridization (RNA-DNA FISH). However, it is difficult to
      preserve the fragile RNA signals through the harsh conditions used to denature
      the DNA template in DNA FISH. The current protocols of RNA-DNA FISH still cannot
      work robustly in all experiments. RNA-DNA FISH remains as a technically
      challenging and tedious experiment. By incorporating protein components into the
      signal detection steps of RNA FISH, which is then followed by a post-fixation
      step, we established an improved protocol of RNA-DNA FISH. The established method
      worked satisfyingly and robustly in our studies on Xist (inactivated X chromosome
      specific transcript) RNA and Terra (telomeric repeat-containing RNA). Our results
      provided the direct evidence to show that, not all the telomeres are associated
      with Terra, and a significant fraction of Terra foci do not overlap with telomere
      DNA in interphase cell nuclei. The improved method of simultaneous RNA-DNA FISH
      is reliable and time-efficient. It can be used in a variety of biological
      studies.

PMID- 23164509
TI  - Keratin 8/18 regulation of glucose metabolism in normal versus cancerous hepatic
      cells through differential modulation of hexokinase status and insulin signaling.
AB  - As differentiated cells, hepatocytes primarily metabolize glucose for ATP
      production through oxidative phosphorylation of glycolytic pyruvate, whereas
      proliferative hepatocellular carcinoma (HCC) cells undergo a metabolic shift to
      aerobic glycolysis despite oxygen availability. Keratins, the intermediate
      filament (IF) proteins of epithelial cells, are expressed as pairs in a
      lineage/differentiation manner. Hepatocyte and HCC (hepatoma) cell IFs are made
      solely of keratins 8/18 (K8/K18), thus providing models of choice to address
      K8/K18 IF functions in normal and cancerous epithelial cells. Here, we
      demonstrate distinctive increases in glucose uptake, glucose-6-phosphate
      formation, lactate release, and glycogen formation in K8/K18 IF-lacking
      hepatocytes and/or hepatoma cells versus their respective IF-containing
      counterparts. We also show that the K8/K18-dependent glucose uptake/G6P formation
      is linked to alterations in hexokinase I/II/IV content and localization at
      mitochondria, with little effect on GLUT1 status. In addition, we find that the
      insulin-stimulated glycogen formation in normal hepatocytes involves the main PI
      3 kinase-dependent signaling pathway and that the K8/K18 IF loss makes them more
      efficient glycogen producers. In comparison, the higher insulin-dependent
      glycogen formation in K8/K18 IF-lacking hepatoma cells is associated with a
      signaling occurring through a mTOR-dependent pathway, along with an augmentation
      in cell proliferative activity. Together, the results uncover a key K8/K18
      regulation of glucose metabolism in normal and cancerous hepatic cells through
      differential modulations of mitochondrial HK status and insulin-mediated
      signaling.

PMID- 23164510
TI  - The role of endoscopy in Barrett's esophagus and other premalignant conditions of
      the esophagus.

PMID- 23164511
TI  - Barrett's esophagus: should we burn it all?

PMID- 23164512
TI  - The incidence of "silent" free air and aspiration pneumonia detected by CT after
      gastric endoscopic submucosal dissection.
AB  - BACKGROUND: Although endoscopic submucosal dissection (ESD) is feasible as a
      treatment for early gastric cancer, it requires great skill to perform and may
      place patients at increased risk of a number of complications, including
      perforation and aspiration pneumonia. OBJECTIVE: To investigate the incidence of
      "silent" free air without endoscopic perforation and aspiration pneumonia
      detected by CT after ESD and risk factors for the development of these 2
      conditions. DESIGN: Prospective cohort study. SETTING: Single academic center.
      PATIENTS: This study involved 87 patients with a total of 91 malignancies.
      INTERVENTION: All patients underwent chest and abdominal CT and blood
      biochemistry analysis before and 1 day after ESD. MAIN OUTCOME MEASUREMENTS: The
      incidence of silent free air and aspiration pneumonia after ESD and the related
      risk factors. RESULTS: Silent free air was identified in 37.3% of patients
      without perforation. Tumor location (the upper portion of the stomach), the
      presence of a damaged muscular layer during ESD, and procedure time, but not
      specimen size, were significantly associated with silent free air (P = .006, P =
      .04, P = .02, and P = .53, respectively). According to the receiver-operating
      characteristic analysis, the resulting cutoff value of the procedure time for
      silent free air was 105 minutes (67.7% sensitivity, 65.4% specificity). Only
      procedure time (>= 105 minutes) was an independent predictor of silent free air
      development (odds ratio 3.23; 95% confidence interval, 1.21-8.64; P = .02). On
      the other hand, aspiration pneumonia was seen in 6.6% of patients. Silent free
      air and aspiration pneumonia did not affect hospitalization. LIMITATIONS: Single
      center and small number of patients. CONCLUSIONS: Silent free air is frequently
      observed after ESD, and longer procedure time (>= 105 minutes) was an independent
      risk factor for silent free air. However, silent free air and aspiration
      pneumonia detected by CT are not associated with clinically significant
      complications.

PMID- 23164513
TI  - Nonsteroidal anti-inflammatory drugs for prevention of post-ERCP pancreatitis: a
      meta-analysis.
AB  - BACKGROUND: The use of nonsteroidal anti-inflammatory drugs (NSAIDs) in the
      prevention of post-ERCP pancreatitis (PEP) is still controversial. OBJECTIVE: We
      performed a meta-analysis to evaluate the efficacy and safety of NSAIDs for PEP
      prophylaxis. DESIGN: We systematically searched PubMed, EMBASE, Web of Science,
      and the Cochrane Library for relevant studies published updated to June 2012.
      SETTING: Meta-analysis. PATIENTS: Patients undergoing ERCP. INTERVENTIONS: NSAIDs
      use for the prevention of PEP. MAIN OUTCOME MEASUREMENTS: Overall incidence of
      PEP, incidence of moderate to severe PEP, and adverse events. RESULTS: Ten RCTs
      involving 2269 patients were included. Meta-analysis showed that NSAID use
      decreased the overall incidence of PEP (risk ratio [RR], 0.57; 95% CI, 0.38-0.86;
      P = .007). The absolute risk reduction was 5.9%. The number needed to treat was
      17. Heterogeneity among the studies was substantial. However, after removing the
      main source of heterogeneity, the prophylactic efficacy was similar (RR, 0.53;
      95% CI, 0.41-0.68; P < .001). NSAID use also decreased the incidence of moderate
      to severe PEP (RR 0.46; 95% CI, 0.28-0.75; P = .002). The absolute risk reduction
      was 3.0%. The number needed to treat was 34. No differences of the adverse events
      attributable to NSAIDs were observed. LIMITATIONS: Inclusion of low-quality
      studies, different type and route of administration of the NSAIDs, study
      heterogeneity, inconsistent use of pancreatic stenting. CONCLUSIONS: Prophylactic
      use of NSAIDs reduces the incidence and severity of PEP.

PMID- 23164514
TI  - Molecular imaging in GI endoscopy.

PMID- 23164515
TI  - A new accessory, endoscopic cuff, improves colonoscopic access for complex polyp
      resection and scar assessment in the sigmoid colon (with video).
AB  - BACKGROUND: Difficult and unstable endoscopic access to large sessile/flat colon
      polyps in the sigmoid colon may prevent successful and complete EMR. OBJECTIVE:
      We report our experience with the use of an endoscopic cuff, a new endoscopic
      accessory, to improve endoscopic access during endoscopic therapy and scar
      assessment. DESIGN: Single-center, retrospective, feasibility case series.
      SETTING: Tertiary referral academic endoscopy unit. PATIENTS: Nonconsecutive
      patients referred for endoscopic resection of large flat/sessile sigmoid colon
      polyps or surveillance of postpolypectomy scars in the sigmoid colon.
      INTERVENTIONS: When conventional methods to achieve stable access and
      visualization were unsuccessful, the endoscopic cuff was used to retract sigmoid
      colon folds. MAIN OUTCOME MEASUREMENTS: Safety, procedural success, and
      complications. RESULTS: Five patients (mean age 62 years, 3 male/2 female)
      underwent endoscopic cuff-assisted EMR polypectomy, and 7 patients (mean age 62
      years, 2 male/5 female) underwent post-EMR scar surveillance with an endoscopic
      cuff-assisted flexible sigmoidoscopy. All sessile/flat polyps (mean size 29 mm)
      or post-EMR scar sites (mean size 15 mm) were located at acute bends in the
      sigmoid colon. With the endoscopic cuff placed around the tip of the colonoscope,
      endoscopic access improved significantly by flattening/depressing colon folds
      close to the lesion/scar. The entire polyp/scar surface was revealed,
      facilitating a complete polyp excision and a meticulous scar assessment. No
      immediate or delayed adverse events were seen. LIMITATIONS: Single-center,
      nonrandomized case series. CONCLUSIONS: An endoscopic cuff appears to be a safe
      and easily used accessory to facilitate colonoscopic access for complex
      polypectomy and scar assessment in the sigmoid colon.

PMID- 23164516
TI  - Closure of large mucosal defects after endoscopic submucosal dissection: an
      effective technique for preventing complications?

PMID- 23164518
TI  - Sleep deprivation leads to reduction in polyp detection among endoscopy trainees.

PMID- 23164519
TI  - The effects of chelators on zinc levels in patients with thalassemia major.
AB  - Zinc which is an essential element has very important effects on growth and
      immune system in patients with thalassemia major (TM). The effects of two oral
      iron chelator agents, desferrioxamine (DFO) and deferiprone (DFP), on zinc levels
      were investigated in previous studies and they were found to cause zinc
      deficiency. Zinc level alteration by the new chelator deferasirox (DFX) is not
      present in the literature. The aim of this study was to examine the effects of
      different oral chelators on serum and urine zinc levels in TM patients. Zinc
      levels are compared in the patients who received different chelators: only DFX,
      combined chelation with DFO plus DFP and the healthy control group. A total of 56
      patients with TM were involved in this study: 39 patients received only DFX and
      17 patients were given combined treatment DFO+DFP between August 2008 and August
      2009. In addition, a control group was established from the healthy population.
      Blood was taken from all the patients for serum zinc levels and 24hour-urine
      samples were collected for urine zinc levels. Serum zinc levels were found to be
      64.8+/-14.8MUg/dL in DFX group and 66.5+/-15.1MUg/dL in DFO+DFP group. These
      levels were statistically lower than that in the control group (149+/-54.3MUg/dL)
      (p<0.05), but there was no statistically difference between the two different
      chelation groups (p>0.05). The urine zinc levels of DFX and DFO+DFP group were
      662.2+/-428.2MUg/day and 1182.3+/-980.3MUg/day respectively (p<0.05). Urinary
      zinc excretion in the chelation groups (DFX and DFO+DFP) was significantly higher
      than the control group (395.1+/-208.9MUg/day) (p<0.05). As a conclusion, the new
      chelation agent, DFX, also leads to zinc deficiency, though its urinary zinc
      excretion is lower. New studies are required to examine the effects of DFX on
      zinc extensively. Zinc levels of patients with TM should be followed up regularly
      and zinc supply should be given at early ages.

PMID- 23164520
TI  - Association of cord blood levels of lead, arsenic, and zinc with
      neurodevelopmental indicators in newborns: a birth cohort study in Chitwan
      Valley, Nepal.
AB  - In this study, we aimed to investigate the association between in utero toxic
      (lead [Pb] and arsenic [As]) and essential element (zinc [Zn]) levels and
      neurodevelopmental indicators after birth in Chitwan Valley, Nepal. We conducted
      a hospital-based birth cohort study with 100 pregnant women in Chitwan, Nepal. We
      measured Pb, As, and Zn concentrations in cord blood. We assessed 100 infants at
      1 day after birth, using the Brazelton neonatal behavioral assessment scale,
      third edition (NBAS III). Multivariate regression was performed to adjust for
      mother's age, parity, educational level, and body mass index (BMI); family
      income; and newborn's birth weight, gestational age, and age in hours at the time
      of NBAS III assessment. Among the 7 clusters of NBAS III, the motor cluster score
      was inversely associated with the cord blood levels of Pb (coefficient=-2.15, at
      95% confidence interval [CI]=-4.27 to -0.03). The cord blood levels of As were
      inversely associated with the state regulation cluster score (coefficient=-6.71,
      at 95% CI=-12.17 to -1.24). The cord blood levels of Zn were not associated with
      NBAS III scores. The cord blood levels of Pb and As, but not Zn, showed
      significant inverse association with the neurodevelopment of newborns. These
      results suggest that high levels of Pb or As exposure during the prenatal period
      may induce retardation during in utero neurodevelopment.

PMID- 23164521
TI  - Elevated cord serum manganese level is associated with a neonatal high ponderal
      index.
AB  - BACKGROUND: The effects of low-level prenatal manganese (Mn) exposure on neonatal
      growth remain unclear. The level of fetal Mn that may be considered "safe" has
      never been examined. METHODS: A multicenter study including 1377 mother-infant
      pairs was conducted from 2008 through 2009 in Shanghai. Mn concentrations were
      determined for both the cord and maternal serum, as well as neonatal birth weight
      and birth length. The ponderal index (PI) was calculated as (birth weight g/birth
      length cm(3))*100, and a ponderal index >=3.17 was defined as a high ponderal
      index (HPI). RESULTS: The median serum Mn concentration was 4.0MUg/L in the cord
      blood, and was 2.8MUg/L in maternal blood. Of 1377 infants, 135 (9.8%) had a HPI.
      After adjusting for potential confounders, cord serum Mn was not associated with
      birth weight. However, there was a linear relationship between the cord serum Mn
      and the birth length (adjusted beta=-0.5, 95% CI=-0.7 to -0.2, p<0.0001).
      Additionally, a nonlinear relationship was observed between the cord serum Mn and
      the ponderal index, and between the cord serum Mn and HPI. The ponderal index and
      the prevalence of HPI increased with Mn levels above 5.0MUg/L (Log Mn >=0.7). A
      high level of Mn in the cord (>=5.0MUg/L) was associated with a higher ponderal
      index (adjusted beta=0.2, 95% CI=0.1 to 0.2, p<0.001) and a high risk of HPI
      (adjusted OR=3.3, 95% CI=1.8-6.0, p<0.001). CONCLUSIONS: Higher prenatal Mn
      exposure, even at a low level, is associated with a higher prevalence of HPI in a
      nonlinear pattern. Cord serum Mn levels less than 5.0MUg/L may be considered safe
      with respect to neonatal ponderal index assessment.

PMID- 23164522
TI  - Evaluating iterative algebraic algorithms in terms of convergence and image
      quality for cone beam CT.
AB  - Cone beam computed tomography (CBCT) enables a volumetric image reconstruction
      from a set of 2D projection data. It plays an important role in image guided
      radiation therapy (IGRT). However, it is desirable to lower the patient radiation
      dose while maintaining good quality tomographic reconstructions. Hence, methods
      are needed even when the data is undersampled or there are limited projections.
      Iterative algorithms such as ART, SART and OS-SART are known to perform well
      under such circumstances. The performance of ART, SART and OS-SART is here
      studied based on a range of norm measurements (RMS reconstruction error, RMS
      projection error, and the L1 norm and L2 norm of the image error). Image quality
      measurements for uniformity and noise are also introduced. Since image quality
      often degrades as iterative algorithms converge, a simple function is used to
      trade off convergence with image quality. Investigations are performed using
      simulated and experimental data.

PMID- 23164523
TI  - Phase space and power spectral approaches for EEG-based automatic sleep-wake
      classification in humans: a comparative study using short and standard epoch
      lengths.
AB  - Sleep disorders in humans have become a public health issue in recent years.
      Sleep can be analysed by studying the electroencephalogram (EEG) recorded during
      a night's sleep. Alternating between sleep-wake stages gives information related
      to the sleep quality and quantity since this alternating pattern is highly
      affected during sleep disorders. Spectral composition of EEG signals varies
      according to sleep stages, alternating phases of high energy associated to low
      frequency (deep sleep) with periods of low energy associated to high frequency
      (wake and light sleep). The analysis of sleep in humans is usually made on
      periods (epochs) of 30-s length according to the original Rechtschaffen and Kales
      sleep scoring manual. In this work, we propose a new phase space-based (mainly
      based on Poincare plot) algorithm for automatic classification of sleep-wake
      states in humans using EEG data gathered over relatively short-time periods. The
      effectiveness of our approach is demonstrated through a series of experiments
      involving EEG data from seven healthy adult female subjects and was tested on
      epoch lengths ranging from 3-s to 30-s. The performance of our phase space
      approach was compared to a 2-dimensional state space approach using the power
      spectral (PS) in two selected human-specific frequency bands. These powers were
      calculated by dividing integrated spectral amplitudes at selected human-specific
      frequency bands. The comparison demonstrated that the phase space approach gives
      better performance in the case of short as well as standard 30-s epoch lengths.

PMID- 23164524
TI  - Texture and color based image segmentation and pathology detection in capsule
      endoscopy videos.
AB  - This paper presents an in-depth study of several approaches to exploratory
      analysis of wireless capsule endoscopy images (WCE). It is demonstrated that
      versatile texture and color based descriptors of image regions corresponding to
      various anomalies of the gastrointestinal tract allows their accurate detection
      of pathologies in a sequence of WCE frames. Moreover, through classification of
      single pixels described by texture features of their neighborhood, the images can
      be segmented into homogeneous areas well matched to the image content. For both,
      detection and segmentation tasks the same procedure is applied which consists of
      features calculation, relevant feature subset selection and classification
      stages. This general three-stage framework is realized using various recognition
      strategies. In particular, the performance of the developed Vector Supported
      Convex Hull classification algorithm is compared against Support Vector Machines
      run in configuration with two different feature selection methods. 

PMID- 23164525
TI  - What do we want to see and how?

PMID- 23164526
TI  - Value of a preoperative checklist for laparoscopic appendectomy and
      cholecystectomy.
AB  - Laparoscopy is a complex technique where incidents related to equipment
      failure/malfunction commonly occur. The purpose of the WHO preoperative safety
      checklist is to significantly reduce surgically associated complications and
      mortality. GOAL: The goal of this study was to show that a preoperative checklist
      for laparoscopy could improve procedure efficiency by reducing lost time due to
      these incidents. MATERIAL AND METHODS: This prospective study compared the
      occurrence of incidents related to equipment, patient installation and the time
      loss attributed to these incidents, before and after the initiation of a
      preoperative checklist. Two hundred consecutive laparoscopic procedures
      (appendectomies and cholecystectomies) were studied; the first hundred without
      the preoperative checklist and the second hundred after the initiation of this
      laparoscopic checklist. RESULTS: The risk of at least one incident to occur
      during the procedure was increased 3-fold ([1.36 vs. 6.64], P=0.007) when the
      checklist was not used compared to when the preoperative checklist was used.
      Likewise, the number of incidents increased 2.4-fold ([1.15; 5.01], P=0.02),
      compared to when the preoperative checklist was used. The checklist significantly
      reduced the proportion of incidences during which time was lost from 22% to 10%
      (P=0.03). CONCLUSION: A preoperative checklist for laparoscopic procedures is
      feasible and seems useful to prevent adverse events in the operating room.

PMID- 23164527
TI  - Mainstreaming sex and gender analysis in public health genomics.
AB  - BACKGROUND: The integration of genome-based knowledge into public health or
      public health genomics (PHG) aims to contribute to disease prevention, health
      promotion, and risk reduction associated with genetic disease susceptibility. Men
      and women differ, for instance, in susceptibilities for heart disease, obesity,
      or depression due to biologic (sex) and sociocultural (gender) factors and their
      interaction. Genome-based knowledge is rapidly increasing, but sex and gender
      issues are often not explored. OBJECTIVE: To explore the implications of a sex
      and gender analysis for PHG. METHODS: We explore genome-based knowledge in
      relation to sex and gender aspects using depression as an example, gender
      equality, and the intersection of sex and gender with other social stratifiers
      such as ethnic background or socioeconomic status. RESULTS: We advocate a sex-
      and gender-sensitive genomics research agenda alongside studies that provide sex
      disaggregated data rather than controls based on sex. Such a research agenda is
      needed to guide research on how genomics is understood and perceived by men and
      women across groups, and for the equitable and responsible translation of such
      knowledge into the public health domain. CONCLUSIONS: Including sex and gender
      analysis in PHG research will not only shed more light on phenomena such as
      diseases with a higher prevalence in either men or women, but will ultimately
      lead to gendered innovations by way of exploring how gendered and cultural
      environments increase or safeguard genetic predispositions.

PMID- 23164528
TI  - Sex and life expectancy.
AB  - BACKGROUND: A sexual dimorphism in human life expectancy has existed in almost
      every country for as long as records have been kept. Although human life
      expectancy has increased each year, females still live longer, on average, than
      males. Undoubtedly, the reasons for the sex gap in life expectancy are
      multifaceted, and it has been discussed from both sociological and biological
      perspectives. However, even if biological factors make up only a small percentage
      of the determinants of the sex difference in this phenomenon, parity in average
      life expectancy should not be anticipated. OBJECTIVE: The aim of this review is
      to highlight biological mechanisms that may underlie the sexual dimorphism in
      life expectancy. METHODS: Using PubMed, ISI Web of Knowledge, and Google Scholar,
      as well as cited and citing reference histories of articles through August 2012,
      English-language articles were identified, read, and synthesized into categories
      that could account for biological sex differences in human life expectancy.
      RESULTS: The examination of biological mechanisms accounting for the female-based
      advantage in human life expectancy has been an active area of inquiry; however,
      it is still difficult to prove the relative importance of any 1 factor.
      Nonetheless, biological differences between the sexes do exist and include
      differences in genetic and physiological factors such as progressive skewing of X
      chromosome inactivation, telomere attrition, mitochondrial inheritance, hormonal
      and cellular responses to stress, immune function, and metabolic substrate
      handling among others. These factors may account for at least a part of the
      female advantage in human life expectancy. CONCLUSIONS: Despite noted gaps in sex
      equality, higher body fat percentages and lower physical activity levels globally
      at all ages, a sex-based gap in life expectancy exists in nearly every country
      for which data exist. There are several biological mechanisms that may contribute
      to explaining why females live longer than men on average, but the complexity of
      the human life experience makes research examining the contribution of any single
      factor for the female advantage difficult. However, this information may still
      prove important to the development of strategies for healthy aging in both sexes.

PMID- 23164529
TI  - New insights into thyroglobulin gene: molecular analysis of seven novel mutations
      associated with goiter and hypothyroidism.
AB  - The thyroglobulin (TG) gene is organized in 48 exons, spanning over 270 kb on
      human chromosome 8q24. Up to now, 62 inactivating mutations in the TG gene have
      been identified in patients with congenital goiter and endemic or non-endemic
      simple goiter. The purpose of the present study was to identify and characterize
      new mutations in the TG gene. We report 13 patients from seven unrelated families
      with goiter, hypothyroidism and low levels of serum TG. All patients underwent
      clinical, biochemical and imaging evaluation. Single-strand conformation
      polymorphism (SSCP) analysis, endonuclease restriction analysis, sequencing of
      DNA, genotyping, population screening, and bioinformatics studies were performed.
      Molecular analyses revealed seven novel inactivating TG mutations: c.378C>A
      [p.Y107X], c.2359C>T [p.R768X], c.2736delG [p.R893fsX946], c.3842G>A [p.C1262Y],
      c.5466delA [p.K1803fsX1833], c.6000C>G [p.C1981W] and c.6605C>G [p.P2183R] and
      three previously reported mutations: c.886C>T [p.R277X], c.6701C>A [p.A2215D] and
      c.7006C>T [p.R2317X]. Six patients from two families were homozygous for p.R277X
      mutation, four were compound heterozygous mutations (p.Y107X/p.C1262Y,
      p.R893fsX946/p.A2215D, p.K1803fsX1832/p.R2317X), one carried three identified
      mutations (p.R277X/p.C1981W-p.P2183R) together with a hypothetical micro deletion
      and the remaining two siblings from another family with typical phenotype had a
      single p.R768X mutated allele. In conclusion, our results confirm the genetic
      heterogeneity of TG defects and the pathophysiological importance of altered TG
      folding as a consequency of truncated TG proteins and missense mutations located
      in ACHE-like domain or that replace cysteine.

PMID- 23164530
TI  - Nurse mentorship to improve the quality of health care delivery in rural Rwanda.
AB  - Quality of care at rural health centers in Rwanda is often limited by gaps in
      individual nurses' knowledge and skills, as well as systems-level issues, such as
      supply and human resource management. Typically, nurse training is largely
      didactic and supervision infrequent. Partners In Health and the Rwandan Ministry
      of Health (MOH) collaborated to implement the nurse-focused Mentoring and
      Enhanced Supervision at Health Centers (MESH) program. Rwandan nurse-mentors
      trained in quality improvement and mentoring techniques were integrated into the
      MOH's district supervisory team to provide ongoing, on-site individual mentorship
      to health center nurses and to drive systems-level quality improvement
      activities. The program targeted 21 health centers in two rural districts and
      supported implementation of MOH evidence-based protocols. Initial results
      demonstrate significant improvement in a number of quality-of-care indicators.
      Emphasis on individual provider and systems-level issues, integration within MOH
      systems, and continuous monitoring efforts were instrumental to these early
      successes.

PMID- 23164532
TI  - The effects of monovalent and divalent cations on the stability of silver
      nanoparticles formed from direct reduction of silver ions by Suwannee River humic
      acid/natural organic matter.
AB  - The formation and characterization of AgNPs (silver nanoparticles) formed from
      the reduction of Ag+ by SRNOM (Suwannee River natural organic matter) is
      reported. The images of SRNOM-formed AgNPs and the selected area electron
      diffraction (SAED) were captured by high resolution transmission electron
      microscopy (HRTEM). The colloidal and chemical stability of SRNOM- and SRHA
      (Suwannee River humic acid)-formed AgNPs in different ionic strength solutions of
      NaCl, KCl, CaCl2 and MgCl2 was investigated in an effort to evaluate the key fate
      and transport processes of these nanoparticles in natural aqueous environments.
      The aggregation state, stability and sedimentation rate of the AgNPs were
      monitored by Dynamic Light Scattering (DLS), zeta potential, and UV-vis
      measurements. The results indicate that both types of AgNPs are very unstable in
      high ionic strength solutions. Interestingly, the nanoparticles appeared more
      unstable in divalent cation solutions than in monovalent cation solutions at
      similar concentrations. Furthermore, the presence of SRNOM and SRHA contributed
      to the nanoparticle instability at high ionic strength in divalent metallic
      cation solutions, most likely due to intermolecular bridging with the organic
      matter. The results clearly suggest that changes in solution chemistry greatly
      affect nanoparticle long term stability and transport in natural aqueous
      environments.

PMID- 23164531
TI  - Sustaining rapid vesicular release at active zones: potential roles for vesicle
      tethering.
AB  - Rapid information processing in our nervous system relies on high-frequency
      fusion of transmitter-filled vesicles at chemical synapses. Some sensory synapses
      possess prominent electron-dense ribbon structures that provide a scaffold for
      tethering synaptic vesicles at the active zone (AZ), enabling sustained vesicular
      release. Here, we review functional data indicating that some central and
      neuromuscular synapses can also sustain vesicle-fusion rates that are comparable
      to those of ribbon-type sensory synapses. Comparison of the ultrastructure across
      these different types of synapses, together with recent work showing that
      cytomatrix proteins can tether vesicles and speed vesicle reloading, suggests
      that filamentous structures may play a key role in vesicle supply. We discuss
      potential mechanisms by which vesicle tethering could contribute to sustained
      high rates of vesicle fusion across ribbon-type, central, and neuromuscular
      synapses.

PMID- 23164533
TI  - Is lung transplantation survival better in infants? Analysis of over 80 infants.
AB  - BACKGROUND: There have been >1,600 pediatric lung transplantations (LTx)
      performed worldwide with a trend toward improved outcomes over the last 25 years.
      The majority of these LTxs have been in older children and adolescents. Less than
      4 infant (defined as <= 12 months of age) LTxs per year have been performed over
      the past 20 years, mostly in the USA. However, infant LTx outcomes have not been
      well documented in a multi-institutional longitudinal fashion. METHODS: The
      United Network of Organ Sharing database was queried from October 1987 to July
      2011. Of the 1,003 pediatric LTxs reported, 84 (8%) were infants. All combined
      transplantations were excluded. RESULTS: Eighty-one infants received 84 LTxs, of
      which 95% had a bilateral LTx. Median age and weight at LTx was 4 months (range 0
      to 11 months) and 5.3 kg (2.7 to 11.8 kg), respectively. Median ischemic time was
      5.2 hours (2.0 to 10.8 hours). Overall Kaplan-Meier graft survival was similar
      for infants compared with other pediatric age group (OPA: >1 to 18 years) LTx
      recipients (half-life 4.0 years vs 3.4 years, p = 0.7). Conditional 1-year graft
      survival for infants was significantly higher than OPA (half-life 7.4 years vs
      5.0 years, p = 0.024). Early (1987 to 2000, n = 46) and late (2001 to 2011, n =
      38) era graft survival was not significantly different. Graft survival in pre-LTx
      ventilated infants was significantly better than pre-LTx ventilated OPA (half
      life 6.1 years vs 0.9 year, p = 0.004) and was not statistically different from
      pre-LTx infants not on ventilatory support (half-life 6.1 years vs 2.2 years, p =
      0.152). Cox regression of 5 variables (weight, donor arterial PO(2), pre-Tx
      ventilator, organ ischemic time, center experience) showed that survival was
      associated with increased center experience (p = 0.03). CONCLUSION: Infants
      undergoing LTx have outcomes similar to those of all other pediatric LTx
      patients.

PMID- 23164534
TI  - Patients with low compared with high body mass index gain more weight after
      implantation of a continuous-flow left ventricular assist device.
AB  - BACKGROUND: Patterns of weight change after implantation of a continuous-flow
      left ventricular assist device (CF-LVAD) can affect transplant candidacy and may
      influence outcomes. We evaluated changes in weight over a 24-month period from a
      national LVAD clinical trial database. METHODS: A retrospective analysis was
      performed of 896 patients enrolled into the HeartMate II Clinical trials for
      bridge-to-transplant and destination therapy from March 2005 to January 2009. The
      patients were divided into 4 groups: underweight (body mass index [BMI] <18.5
      [kg/m(2)]); normal (BMI 18.5 to 29.9); obese (BMI 30 to 34.9); and extremely
      obese (BMI >= 35). Baseline BMI was compared with BMI at 6 months and 24 months
      after implant. BMI change >10% of baseline was considered clinically significant.
      RESULTS: At 6 months, underweight and normal-weight patients had significant
      increases in BMI, with effects sustained up to 24 months (p < 0.01). Underweight
      patients gained weight most often, with 75% showing clinically meaningful weight
      gain at 24 months. Obese and extremely obese patients, in contrast, did not
      experience weight change over the same period. Pre-albumin levels improved from
      baseline to 6 months in all patients. CONCLUSIONS: Underweight and normal-weight
      patients had an increase in BMI after LVAD implantation, and these changes
      persisted through 24 months. The BMIs of obese and extremely obese patients
      remained unchanged. Nutritional status improved in all groups.

PMID- 23164535
TI  - Accurate assessment of load-independent right ventricular systolic function in
      patients with pulmonary hypertension.
AB  - BACKGROUND: End-systolic elastance (E(es)), a load-independent measure of
      ventricular function, is of clinical interest for studies of the right ventricle
      (RV) in patients with pulmonary arterial hypertension (PAH). The objective of
      this study was to determine whether, in PAH patients, E(es) can be estimated from
      mean pulmonary artery pressure (mPAP) and end-systolic volume (ESV) only.
      METHODS: Right heart catheterization was used to measure mPAP. Maximal isovolumic
      pressure (P(iso)) was estimated from RV pressure curves with the so-called single
      beat method. Cardiac magnetic resonance imaging (MRI) was used to assess RV end
      diastolic and end-systolic volumes (EDV and ESV). E(es) was then calculated as:
      E(es) = (P(iso)-mPAP) / (EDV-ESV), and as E(es,V0 = 0) = mPAP/ESV (simplified
      method, with V0 = 0, is negligible volume at zero pressure). Right ventricular
      volume at zero pressure (V(0)) was then defined as the intercept of the end
      systolic pressure-volume relation (single-beat method) with the horizontal axis.
      RESULTS: E(es,V0 = 0) was significantly lower compared with E(es) (0.61 vs 1.34
      mm Hg/ml, respectively, p<0.01). A modified Bland-Altman analysis showed a
      contractility-dependent difference between E(es,V0 = 0) and E(es). Moreover, V(0)
      ranged from-8 up to 171 ml, and a moderate and good correlation was found between
      V(0) and EDV, and V(0) and ESV, respectively (r = 0.65 and r = 0.87, p< 0.01).
      CONCLUSIONS: These findings show that V(0) is dependent on RV dilation.
      Therefore, the assumption that V(0) is negligible in PAH is incorrect.
      Consequently, for an accurate assessment of load-independent RV systolic
      function, RV volumes and pressure curves are required.

PMID- 23164536
TI  - Photooxidation and antioxidant responses in the earthworm Amynthas gracilis
      exposed to environmental levels of ultraviolet B radiation.
AB  - Ultraviolet (UV) radiation leads to photooxidation in various organisms. Our
      previous study demonstrated that ultraviolet B (UV-B) radiation is lethal for
      particular species of earthworms, but the mechanisms responsible for the
      lethality are unclear. In our current study, we investigated that ultraviolet
      light causes photooxidative damage and reduces antioxidant responses in the
      earthworm Amynthas gracilis. Intact earthworms and skin/muscle tissue extracts
      were exposed to UV-B radiation for in vivo and in vitro studies. Both in vitro
      and in vivo results showed that the products of photooxidative damage, MDA and
      H(2)O(2), increased after UV-B exposure. Glutathione peroxidase (GPx) and
      catalase were inhibited immediately after exposure to high doses (3000J/m(2)) of
      UV-B radiation in vivo. Catalase activity was increased following a low UV-B dose
      (500J/m(2)) in vivo, but decreased in response to all dosage levels in vitro.
      These data indicate that a relationship exists between UV-B induced damage and
      photooxidation and also that catalase and GPx act as important antioxidants to
      prevent photooxidation. According to these data, A. gracilis exhibits high
      sensitivity to environmental levels of UV-B. Therefore, A. gracilis represents a
      sensitive and cost-effective model organism for investigations of UV-radiation
      damage and environmental UV stress.

PMID- 23164537
TI  - Intestinal perfusion indicates high reliance on paracellular nutrient absorption
      in an insectivorous bat Tadarida brasiliensis.
AB  - Flying vertebrates have been hypothesized to have a high capacity for
      paracellular absorption of nutrients. This could be due to high permeability of
      the intestines to nutrient-sized molecules (i.e., in the size range of amino
      acids and glucose, MW 75-180 Da). We performed intestinal luminal perfusions of
      an insectivorous bat, Tadarida brasiliensis. Using radio-labeled molecules, we
      measured the uptake of two nutrients absorbed by paracellular and transporter
      mediated mechanisms (L-proline, MW 115 Da, and D-glucose, MW 180 Da) and two
      carbohydrates that have no mediated transport (L-arabinose, MW 150 Da, and
      lactulose, MW 342 Da). Absorption of lactulose (0.61+/-0.06 nmol min(-1) cm(-1))
      was significantly lower than that of the smaller arabinose (1.09+/-0.04 nmol min(
      1) cm(-1)). Glucose absorption was significantly lower than that of proline at
      both nutrient concentrations (10mM and 75 mM). Using the absorption of arabinose
      to estimate the portion of proline absorption that is paracellular, we calculated
      that 25.1+/-3.0% to 66.2+/-7.8% of proline absorption is not transporter-mediated
      (varying proline from 1 mM to 75 mM). These results confirm our predictions that
      1) paracellular absorption is molecule size selective, 2) absorption of proline
      would be greater than glucose absorption in an insectivore, and 3) paracellular
      absorption represents a large fraction of total nutrient absorption in bats.

PMID- 23164538
TI  - Aging gonads, glands, and gametes: immutable or partially reversible changes?
AB  - Decreased ovarian testosterone production, granulosa cell dysfunction, oocyte
      telomere shortening and mitochondrial defects, and sperm DNA fragmentation all
      contribute to reproductive aging. Maneuvers aimed at correcting these
      abnormalities, including reduction of oxidative stress, improved lifestyle and
      nutrition, and the role of supplements, are reviewed.

PMID- 23164539
TI  - Null genotypes of GSTM1 and GSTT1 contribute to male factor infertility risk: a
      meta-analysis.
AB  - OBJECTIVE: To study the null of GSTM1, GSTT1, or GSTT1-GSTM1 and the risk of male
      factor infertility. DESIGN: Meta-analysis using electronic databases (Pubmed,
      Medline, Embase, and China National Knowledge Infrastructure) up to August 22,
      2011. SETTING: The strength of the relationship between the null of GSTM1, GSTT1,
      and GSTT1-GSTM1 and the risk of male factor infertility was assessed by odds
      ratios (ORs). A total of 16 studies were identified in this meta-analysis. Among
      the 16 studies, 15 studies reported GSTM1null, 10 reported GSTT1, and five
      reported GSTM1-GSTT1. PATIENT(S): Male infertility patients and a fertile control
      group. INTERVENTION(S): Meta-analyses by means of random-effects models and fixed
      effects models. MAIN OUTCOME MEASURE(S): Ratio of male factor infertility.
      RESULT(S): The studies provided overall OR estimates for GSTM1, GSTT1, and GSTM1
      GSTT1, leading to a pooled OR of 1.41 (95% confidence interval [CI], 1.10-1.81),
      1.15 (95% CI, 0.95-1.39), and 2.99 (95% CI, 2.14-4.18), respectively.
      CONCLUSION(S): There was evidence that the null of GSTM1 and GSTM1-GSTM1
      increased the risk of male factor infertility, but the null genotype of GSTT1 was
      not associated with an increased infertility risk. We still need further
      multicenter and better controlled studies to confirm these findings.

PMID- 23164540
TI  - Assessing the impacts of droughts on net primary productivity in China.
AB  - Frequency and severity of droughts were projected to increase in many regions.
      However, their effects of temporal dynamics on the terrestrial carbon cycle
      remain uncertain, and hence deserve further investigation. In this paper, the
      droughts that occurred in China during 2001-2010 were identified by using the
      standardized precipitation index (SPI). Standardized anomaly index (SAI), which
      has been widely employed in reflecting precipitation, was extended to evaluate
      the anomalies of net primary productivity (NPP). In addition, influences of the
      droughts on vegetation were explored by examining the temporal dynamics of SAI
      NPP along with area-weighted drought intensity at different time scales (1, 3, 6,
      9 and 12 months). Year-to-year variability of NPP with several factors, including
      droughts, NDVI, radiation and temperature, was analyzed as well. Consequently,
      the droughts in the years 2001, 2006 and 2009 were well reconstructed. This
      indicates that SPI could be applied to the monitoring of the droughts in China
      during the past decade (2001-2010) effectively. Moreover, strongest correlations
      between droughts and NPP anomalies were found during or after the drought
      intensities reached their peak values. In addition, some droughts substantially
      reduced the countrywide NPP, whereas the others did not. These phenomena can be
      explained by the regional diversities of drought intensity, drought duration,
      areal extents of the droughts, as well as the cumulative and lag responses of
      vegetation to the precipitation deficits. Besides the drought conditions,
      normalized difference vegetation index (NDVI), radiation and temperature also
      contribute to the interannual variability of NPP.

PMID- 23164541
TI  - Potential distribution of an invasive species under climate change scenarios
      using CLIMEX and soil drainage: a case study of Lantana camara L. in Queensland,
      Australia.
AB  - Invasive species pose a major threat to biodiversity which may be intensified by
      the effects of climate change, particularly if favourable climate conditions
      allow invasives to spread to new areas. This research explores the combined
      effects of climate change and soil drainage on the potential future distribution
      of Lantana camara L. (lantana) in Queensland, Australia. Lantana is an invasive
      woody shrub species that has a profound economic and environmental impact
      worldwide. CLIMEX was used to develop a process-based niche model of lantana to
      estimate its potential distribution under current and future climate. Two Global
      Climate Models (GCMs), CSIRO-Mk3.0 and MIROC-H, were used to explore the impacts
      of climate change. These models were run with the A1B and A2 scenarios for 2030,
      2070 and 2100. Further refinements of the potential distributions were carried
      out through the integration of fine scale soil drainage data in a Geographic
      Information System (GIS). The results from both GCMs show a progressive reduction
      in climatic suitability for lantana in Queensland. The MIROC-H projects a larger
      area as remaining at risk of lantana invasion in 2100 compared to CSIRO-Mk3.0.
      Inclusion of soil drainage data results in a more refined distribution. Overall
      results show a dramatic reduction in potential distribution of lantana in
      Queensland in the long term (2100). However, in the short term (2030), areas such
      as South East Queensland and the Wet Tropics, both regions of significant
      ecological importance, remain at risk of invasion consistently under both GCMs
      and with both the climate only and climate and soil drainage models. Management
      of lantana in these regions will need to be prioritized to protect environmental
      assets of ecological significance.

PMID- 23164542
TI  - The economic efficiency of conservation measures for amphibians in organic
      farming--results from bio-economic modelling.
AB  - This paper presents a whole farm bio-economic modelling approach for the
      assessment and optimisation of amphibian conservation conditions applied at the
      example of a large scale organic farm in North-Eastern Germany. The assessment
      focuses mainly on the habitat quality as affected by conservation measures such
      as through specific adapted crop production activities (CPA) and in-field buffer
      strips for the European tree frog (Hyla arborea), considering also interrelations
      with other amphibian species (i.e. common spadefoot toad (Pelobates fuscus), fire
      bellied toad (Bombina bombina)). The aim of the approach is to understand,
      analyse and optimize the relationships between the ecological and economic
      performance of an organic farming system, based on the expectation that
      amphibians are differently impacted by different CPAs. The modelling system
      consists of a set of different sub-models that generate a farm model on the basis
      of environmentally evaluated CPAs. A crop-rotation sub-model provides a set of
      agronomically sustainable crop rotations that ensures overall sufficient nitrogen
      supply and controls weed, pest and disease infestations. An economic sub-model
      calculates the gross margins for each possible CPA including costs of inputs such
      as labour and machinery. The conservation effects of the CPAs are assessed with
      an ecological sub-model evaluates the potential negative or positive effect that
      each work step of a CPA has on amphibians. A mathematical programming sub-model
      calculates the optimal farm organization taking into account the limited factors
      of the farm (e.g. labour, land) as well as ecological improvements. In sequential
      model runs, the habitat quality is to be improved by the model, while the highest
      possible gross margin is still to be achieved. The results indicate that the
      model can be used to show the scope of action that a farmer has to improve
      habitat quality by reducing damage to amphibian population on its land during
      agricultural activities. Thereby, depending on the level of habitat quality that
      is aimed at, different measures may provide the most efficient solution. Lower
      levels of conservation can be achieved with low-cost adapted CPAs, such as an
      increased cutting height, reduced sowing density and grubbing instead of
      ploughing. Higher levels of conservation require e.g. grassland-like managed
      buffer strips around ponds in sensible areas, which incur much higher on-farm
      conservation costs.

PMID- 23164543
TI  - Upregulation of PVN CRHR1 by gestational intermittent hypoxia selectively
      triggers a male-specific anxiogenic effect in rat offspring.
AB  - We previously reported that gestational intermittent hypoxia (GIH) causes anxiety
      like behavior in neonatal rats. Here, we showed that the anxiogenic effect was
      correlated with upregulation of corticotropin-releasing hormone receptor 1
      (CRHR1) in the hypothalamic paraventricular nuclei (PVN) by GIH, and was
      selective to male offspring. The anxiety-like behavior was assessed by both the
      open field (OF) and elevated plus maze (EPM) tests. We demonstrated that GIH
      triggered anxiety-like behavior in male offspring, but not in female offspring or
      in the postpartum dams. Microinjection of antalarmin, a CRHR1-selective
      antagonist, into the PVN of the male offspring significantly increased the
      distance traveled and time spent in the central portion of the OF, and the time
      spent in the open arms in the EPM compared with controls. However, microinjection
      of the CRHR2 agonist, urocortin III, into the PVN did not affect anxiogenic
      behavior in the male offspring. These findings clearly demonstrate a gender
      selective effect of GIH to increase anxiety-like behavior and this anxiogenic
      effect might be linked to embryogenically-driven upregulation of PVN CRHR1.

PMID- 23164544
TI  - Editorial--Singapore Malaria Network Meeting (SingMalNet) 2012.

PMID- 23164545
TI  - Smurf E3 ubiquitin ligases at the cross roads of oncogenesis and tumor
      suppression.
AB  - Smad ubiquitin regulatory factors (Smurfs) belong to the HECT- family of E3
      ubiquitin ligases and comprise mainly of two members, Smurf1 and Smurf2.
      Initially, Smurfs have been implicated in determining the competence of cells to
      respond to TGF-beta/BMP signaling pathway. Nevertheless, the intrinsic catalytic
      activity has extended the repertoire of Smurf substrates beyond the TGF-beta/BMP
      super family expanding its realm further to epigenetic modifications of histones
      governing the chromatin landscape. Through regulation of a large number of
      proteins in multiple cellular compartments, Smurfs regulate diverse cellular
      processes, including cell-cycle progression, cell proliferation, differentiation,
      DNA damage response, maintenance of genomic stability, and metastasis. As the
      genomic ablation of Smurfs leads to global changes in histone modifications and
      predisposition to a wide spectrum of tumors, Smurfs are also considered to have a
      novel tumor suppressor function. This review focuses on regulation network and
      biological functions of Smurfs in connection with its role in cancer progression.
      By providing a portrait of their protein targets, we intend to link the substrate
      specificity of Smurfs with their contribution to tumorigenesis. Since the
      regulation and biological functions of Smurfs are quite complex, understanding
      the oncogenic potential of these E3 ubiquitin ligases may facilitate the
      development of mechanism-based drugs in cancer treatment.

PMID- 23164546
TI  - SLC34A2 Gene mutation of pulmonary alveolar microlithiasis: report of four cases
      and review of literatures.
AB  - Pulmonary alveolar microlithiasis (PAM) is a rare autosomal recessive disorder
      characterized by the deposition of calcium phosphate microliths throughout the
      lungs. Currently the mutation of SLC34A2 gene was considered responsible for PAM.
      Here we reported the studies on mutation analysis of the SLC34A2 gene in three
      familial members and one unrelated subject of PAM by DNA direct sequencing.
      Meanwhile, we also reviewed and analyzed the published studies of the SLC34A2
      gene mutation in PAM patients. The three familial patients were siblings of an
      inbred family whose parents were cousins. All four patients presented recurrent
      cough and exertional dyspnea. Diagnosis of PAM was made according to the typical
      manifestation of radiology. One homozygous mutation of the SLC34A2 gene, c.910A >
      T (p.K304X) was identified. The review of the SLC34A2 gene mutation showed
      multiple mutation symbols in PAM patients from China, Turkey, and Japan
      respectively. The present study supports that the clinical features, pathological
      and radiological characteristics of Chinese PAM patients are similar to those
      reported in other countries. Our investigation revealed that the c.910A > T
      mutation in the SCL34A2 gene was responsible for PAM patients in China. The
      review of literatures suggests that exon7 and exon8 seemed liable to be affected
      typical Mongoloid of PAM, and exon8 might be the screen target for Chinese
      patients.

PMID- 23164547
TI  - Muscle strength is the main associated factor of physical performance in older
      adults with knee osteoarthritis regardless of radiographic severity.
AB  - The aim of the study is to compare factors associated with physical performance
      in older individuals with severe knee osteoarthritis and those with less-severe
      osteoarthritis. This is an ancillary cross-sectional study to a population-based
      cohort study focusing on Koreans age 65 years or older. The analysis included 553
      subjects with information about knee pain, depressive symptoms, and comorbidities
      collected by self-reported questionnaire, and body weight, knee osteoarthritis
      severity, muscle strength, and physical measures by observer-rated tests.
      Stepwise logistic regression analyses were performed with physical performance as
      an outcome variable and the others as independent variables across radiographic
      knee osteoarthritis severity. In the minimal-to-moderate-severity group, muscle
      strength, knee pain, BMI, and age were related to poor performance (OR [CI] 0.81
      [0.73-0.90], 1.12 [1.03-1.21], 0.87 [0.79-0.96], and 1.09 [1.05-1.14],
      respectively). In the severe group, muscle strength was the only factor
      significantly associated with poor performance (OR [CI] 0.72 [0.58-0.89]). Muscle
      strength, knee pain, and BMI were important determinants of physical performance
      in the older population with knee osteoarthritis. In severe knee osteoarthritis
      patients, muscle strength was the only significant determinant.

PMID- 23164548
TI  - Improving Alzheimer's disease phase II clinical trials.
AB  - Over the past 30 years, many drugs have been studied as possible treatments for
      Alzheimer's disease, but only four have demonstrated sufficient efficacy to be
      approved as treatments, of which three are in the same class. This lack of
      success has raised questions both in the pharmaceutical industry and academia
      about the future of Alzheimer's disease therapy. The high cost and low success
      rate of drug development across many disease areas can be attributed, in large
      part, to late-stage clinical failures (Schachter and Ramoni, Nat Rev Drug Discov
      2007;6:107-8). Thus, identifying in phase II, or preferably phase I, drugs that
      are likely to fail would have a dramatic impact on the costs associated with
      developing new drugs. With this in mind, the Alzheimer's Association convened a
      Research Roundtable on June 23 and 24, 2011, in Washington, DC, bringing together
      scientists from academia, industry, and government regulatory agencies to discuss
      strategies for improving the probability of phase II trial results predicting
      success when considering the go/no-go decision-making process leading to the
      initiation of phase III.

PMID- 23164550
TI  - Amyloid imaging and cognitive decline in nondemented oldest-old: the 90+ Study.
AB  - BACKGROUND: The goal of this study was to examine cross-sectional and
      longitudinal associations between cognitive performance and beta amyloid (Abeta)
      load determined by florbetapir F18 positron emission tomography (PET) in
      nondemented oldest-old. METHODS: Thirteen nondemented (normal or cognitively
      impaired nondemented) participants (median age, 94.2 years) from The 90+ Study
      underwent florbetapir-PET scanning within 3 months of baseline neuropsychological
      testing. Amyloid load was measured with a semi-automated quantitative analysis of
      average cortical-to-cerebellar standardized uptake value ratio (SUVr) and a
      visual interpretation (Abeta- or Abeta+). Neuropsychological testing was repeated
      every 6 months. RESULTS: At baseline, SUVr correlated significantly with tests of
      global cognition and memory. During follow-up (median, 1.5 years), the Abeta+
      group had steeper declines on most cognitive tests, particularly global cognitive
      measures. CONCLUSION: This preliminary study suggests that greater amyloid load
      is associated with poorer cognition and faster cognitive decline in nondemented
      oldest-old. Amyloid load may identify individuals at increased risk of developing
      Alzheimer's disease.

PMID- 23164551
TI  - Prevalence of mild cognitive impairment subtypes in patients attending a memory
      outpatient clinic--comparison of two modes of mild cognitive impairment
      classification. Results of the Vienna Conversion to Dementia Study.
AB  - BACKGROUND: Early detection of dementia is becoming more and more important owing
      to the advent of pharmacologic treatment. OBJECTIVE: The goals of this study were
      to establish prevalence of mild cognitive impairment (MCI) subtypes in an
      outpatient memory clinic cohort using two different modes of MCI determination.
      DESIGN: Consecutive patients complaining of cognitive problems who came to the
      memory outpatient clinic for assessment of a possible cognitive disorder were
      included in the study. SETTING: Academic medical center. PARTICIPANTS: Six
      hundred eighty consecutive patients complaining about cognitive problems who came
      to the memory outpatient clinic for assessment of a possible cognitive disorder
      and fulfilled the inclusion criteria were included in the study. For 676
      patients, sufficient data for MCI classification were available. RESULTS:
      Categorizing MCI patients into MCI subtypes according to the minimum mode of MCI
      classification revealed the following results: 106 patients (15.7%) were
      categorized as cognitively healthy, whereas 570 patients (84.3%) met the criteria
      for MCI. MCI patients were subtyped as amnestic mild cognitive impairment (aMCI)
      single domain (31 patients; 4.6%), aMCI multiple domain (226 patients; 33.4%),
      non-aMCI single domain (125 patients; 18.5%), and non-aMCI multiple domain (188
      patients; 27.8%). Categorizing MCI patients into MCI subtypes according to the
      mean mode of MCI classification revealed the following results: 409 patients
      (60.5%) were categorized as cognitively healthy, whereas 267 patients (39.5%) met
      the criteria for MCI. MCI patients were subtyped as aMCI single domain (47
      patients; 6.9%), aMCI multiple domain (57 patients; 8.5%), non-aMCI single domain
      (97 patients; 14.3%), and non-aMCI multiple domain (66 patients; 9.8%).
      CONCLUSION: MCI diagnosis frequencies are substantially affected by the criteria
      used for estimation of MCI. The effect of modifying the presence of impairment on
      a single cognitive measure versus the presence of impairment on a mean composite
      score of a certain domain differed considerably, ranging from 39.5% to 84.3%,
      indicating the importance of the development of guidelines for operationalizing
      MCI.

PMID- 23164549
TI  - Neuropsychologic assessment in collaborative Parkinson's disease research: a
      proposal from the National Institute of Neurological Disorders and Stroke Morris
      K. Udall Centers of Excellence for Parkinson's Disease Research at the University
      of Pennsylvania and the University of Washington.
AB  - Cognitive impairment (CI) and behavioral disturbances can be the earliest
      symptoms of Parkinson's disease (PD), ultimately afflict the vast majority of PD
      patients, and increase caregiver burden. Our two Morris K. Udall Centers of
      Excellence for Parkinson's Disease Research were supported by the National
      Institute of Neurological Disorders and Stroke (NINDS) in an effort to recommend
      a comprehensive yet practical approach to cognitive and behavioral assessment to
      further collaborative research. We recommend a stepwise approach with two levels
      of standardized evaluation to establish a common battery, as well as an
      alternative testing recommendation for severely impaired subjects, and review
      supplemental tests that may be useful in specific research settings. Our flexible
      approach may be applied to studies with varying emphasis on cognition and
      behavior, does not place undue burden on participants or resources, and has a
      high degree of compatibility with existing test batteries to promote
      collaboration. 

PMID- 23164552
TI  - Impact of molecular imaging on the diagnostic process in a memory clinic.
AB  - BACKGROUND: [(11)C]Pittsburgh compound B ([(11)C]PIB) and [(18)F]-2-fluoro-2
      deoxy-D-glucose ([(18)F]FDG) PET measure fibrillar amyloid-beta load and glucose
      metabolism, respectively. We evaluated the impact of these tracers on the
      diagnostic process in a memory clinic population. METHODS: One hundred fifty-four
      patients underwent paired dynamic [(11)C]PIB and static [(18)F]FDG PET scans
      shortly after completing a standard dementia screening. Two-year clinical follow
      up data were available for 39 patients. Parametric PET images were assessed
      visually and results were reported to the neurologists responsible for the
      initial diagnosis. Outcome measures were (change in) clinical diagnosis and
      confidence in that diagnosis before and after disclosing PET results. RESULTS:
      [(11)C]PIB scans were positive in 40 of 66 (61%) patients with a clinical
      diagnosis of Alzheimer's disease (AD), 5 of 18 (28%) patients with frontotemporal
      dementia (FTD), 4 of 5 (80%) patients with Lewy body dementia, and 3 of 10 (30%)
      patients with other dementias. [(18)F]FDG uptake patterns matched the clinical
      diagnosis in 38 of 66 (58%) of AD patients, and in 6 of 18 (33%) FTD patients.
      PET results led to a change in diagnosis in 35 (23%) patients. This only occurred
      when prior diagnostic certainty was <90%. Diagnostic confidence increased from 71
      +/- 17% before to 87 +/- 16% after PET (p < .001). Two-year clinical follow-up (n
      = 39) showed that [(11)C]PIB and [(18)F]FDG predicted progression to AD for
      patients with mild cognitive impairment, and that the diagnosis of dementia
      established after PET remained unchanged in 96% of patients. CONCLUSIONS: In a
      memory clinic setting, combined [(11)C]PIB and [(18)F]FDG PET are of additional
      value on top of the standard diagnostic work-up, especially when prior diagnostic
      confidence is low.

PMID- 23164553
TI  - Cutaneous lymphangitis carcinomatosa in a patient with lung adenocarcinoma: case
      report and literature review.
AB  - We report the case of a man with a seven year history of lung adenocarcinoma who
      was diagnosed with cutaneous lymphangitis carcinomatosa. Skin examination
      revealed both an asymptomatic erysepelatoid rash localized on the posterior chest
      and an erythematous, eczematiform, itchy rash on the right anterior chest and on
      the left shoulder. Histopathologic examination of biopsies of these lesions
      revealed the same aspect with an infiltration of the dermal lymphatics by
      metastatic adenocarcinomatous cells. Cutaneous lymphangitis carcinomatosa is a
      rare condition accounting for less than 5% of skin metastases. A literature
      review identified eight other cases of cutaneous lymphangitis carcinomatosa in
      patients with lung cancer.

PMID- 23164554
TI  - Progression-free survival and overall survival in phase III trials of molecular
      targeted agents in advanced non-small-cell lung cancer.
AB  - BACKGROUND: We examined how crossover therapy might affect the association
      between progression-free survival (PFS) and overall survival (OS) in non-small
      cell lung cancer (NSCLC). METHODS: We extracted PFS- and OS-hazard ratios (HRs)
      in phase III trials of molecular-targeted agents for advanced NSCLC. Their
      relationship was modeled in a linear function with the coefficient of
      determination (R-squared) to assess the correlation between PFS and OS. RESULTS:
      Thirty-four trials with 35 pairs for the investigational and reference arms were
      identified (24,158 patients). Overall, there was little correlation between PFS-
      and OS-HRs (R-squared = 0.14), suggesting PFS-HR could account only for 14% of
      variation in OS-HR. The median proportion of crossover therapy per trial was 20%.
      If patients seldom crossed over (none or <1%), the association between PFS- and
      OS-HRs was strong (R-squared = 0.69). When the proportion of crossover was >=1%,
      however, R-squared declined considerably (>=1% to <20% crossover, R-squared =
      0.27; >=20% to <40%, R-squared = 0.06; and >=40%, R-squared = 0.27). CONCLUSIONS:
      A PFS advantage seldom is associated with an OS advantage any longer. Our
      analysis suggests this is due to a high level of crossover now that an increasing
      number of active agents are available for NSCLC.

PMID- 23164556
TI  - From tumor prevention to therapy: empowering p53 to fight back.
AB  - The p53 transcription factor was first described over three decades ago and is
      one of the most studied proteins, with over 60,000 PubMed listed publications.
      Despite being first described as an oncogene, p53 has long been recognized as a
      major tumor suppressor and the most commonly mutated gene in human cancer. The
      frequent inactivation of p53 in tumors fostered the attractive notion that its
      functional reinstatement would constitute an effective tumor-specific therapy.
      Strategies aimed at restoring wild-type p53 function in tumors are being actively
      pursued and some have reached clinical trials, highlighting the important
      translational potential of this new field of research. The therapeutic impact of
      those strategies in human cancer was recently modeled in mice where a clear, even
      if limited, therapeutic benefit of p53-targeted therapies was established. As
      unexpected aspects of p53 tumor suppressive function continue to be uncovered,
      new opportunities arise to further improve p53 therapy outcome. In this review we
      discuss the in vivo mechanisms underlying p53-mediated tumor prevention, the
      impact of p53 functional restoration in tumors and how this knowledge may be
      exploited to improve the efficacy of p53-targeted cancer therapy. A particular
      emphasis is given to the newly identified metabolic functions of p53.

PMID- 23164555
TI  - Understanding resistance to combination chemotherapy.
AB  - The current clinical application of combination chemotherapy is guided by a
      historically successful set of practices that were developed by basic and
      clinical researchers 50-60 years ago. Thus, in order to understand how emerging
      approaches to drug development might aid the creation of new therapeutic
      combinations, it is critical to understand the defining principles underlying
      classic combination therapy and the original experimental rationales behind them.
      One such principle is that the use of combination therapies with independent
      mechanisms of action can minimize the evolution of drug resistance. Another is
      that in order to kill sufficient cancer cells to cure a patient, multiple drugs
      must be delivered at their maximum tolerated dose - a condition that allows for
      enhanced cancer cell killing with manageable toxicity. In light of these models,
      we aim to explore recent genomic evidence underlying the mechanisms of resistance
      to the combination regimens constructed on these principles. Interestingly, we
      find that emerging genomic evidence contradicts some of the rationales of early
      practitioners in developing commonly used drug regimens. However, we also find
      that the addition of recent targeted therapies has yet to change the current
      principles underlying the construction of anti-cancer combinatorial regimens, nor
      have they made substantial inroads into the treatment of most cancers. We suggest
      that emerging systems/network biology approaches have an immense opportunity to
      impact the rational development of successful drug regimens. Specifically, by
      examining drug combinations in multivariate ways, next generation combination
      therapies can be constructed with a clear understanding of how mechanisms of
      resistance to multi-drug regimens differ from single agent resistance.

PMID- 23164557
TI  - Dynamics of glucose and insulin concentration connected to the beta-cell cycle:
      model development and analysis.
AB  - BACKGROUND: Diabetes mellitus is a group of metabolic diseases with increased
      blood glucose concentration as the main symptom. This can be caused by a relative
      or a total lack of insulin which is produced by the beta-cells in the pancreatic
      islets of Langerhans. Recent experimental results indicate the relevance of the
      beta-cell cycle for the development of diabetes mellitus. METHODS: This paper
      introduces a mathematical model that connects the dynamics of glucose and insulin
      concentration with the beta-cell cycle. The interplay of glucose, insulin, and
      beta-cell cycle is described with a system of ordinary differential equations.
      The model and its development will be presented as well as its mathematical
      analysis. The latter investigates the steady states of the model and their
      stability. RESULTS: Our model shows the connection of glucose and insulin
      concentrations to the beta-cell cycle. In this way the important role of glucose
      as regulator of the cell cycle and the capability of the beta-cell mass to adapt
      to metabolic demands can be presented. Simulations of the model correspond to the
      qualitative behavior of the glucose-insulin regulatory system showed in
      biological experiments. CONCLUSIONS: This work focus on modeling the
      physiological situation of the glucose-insulin regulatory system with a detailed
      consideration of the beta-cell cycle. Furthermore, the presented model allows the
      simulation of pathological scenarios. Modification of different parameters
      results in simulation of either type 1 or type 2 diabetes.

PMID- 23164558
TI  - Emergency department contrast practices for abdominal/pelvic computed tomography
      a national survey and comparison with the american college of radiology
      appropriateness criteria((r)).
AB  - BACKGROUND: Controversy exists regarding the need for contrast agents for
      emergency abdominal computed tomography (CT). OBJECTIVES: We surveyed United
      States (US) academic Emergency Departments (EDs) to document national practice.
      We hypothesized variable contrast use for abdominal/pelvic CT, including variance
      from the American College of Radiology's (ACR) Appropriateness Criteria((r)), an
      evidence-based guideline. METHODS: A survey was sent to physician leaders of US
      academic EDs, defined as primary site of an Emergency Medicine residency program.
      Respondents were asked about their institutions' use of oral, intravenous (i.v.),
      and rectal contrast for various abdominal/pelvic CT indications. Responses were
      compared with the approach given the highest appropriateness rating by the
      American College of Radiology. RESULTS: One hundred and six of 152 (70%) surveys
      were completed. Intravenous contrast was the most frequently cited contrast. At
      least 90% of respondents reported using i.v. contrast in 12 of 18 indications.
      Oral contrast use was more variable. In no indication did >=90% of respondents
      indicate use of oral contrast, and in only two indications did >=90% avoid its
      use. Rectal contrast was rarely used. The most common indications for which no
      contrast agent was used were suspected renal colic (79%), viscus perforation
      (19%), penetrating abdominal trauma (18%), and blunt abdominal trauma (15%).
      CONCLUSIONS: Contrast practices for abdominal/pelvic CT vary nationally,
      according to a survey of US academic EDs. For multiple indications, the contrast
      practices of a substantial number of respondents deviated from those
      recommendations given the highest clinical appropriateness rating by the American
      College of Radiology.

PMID- 23164559
TI  - Paving the road for public health initiatives.

PMID- 23164560
TI  - Comparison of total antibody and interferon-gamma T-cell responses in patients
      following infection with brucellosis in Georgia.
AB  - Brucellosis is an ancient disease that still remains a significant threat to
      humans and is typically linked to exposure to infected animals and/or consumption
      of unpasteurized animal products. Despite this history, we have a relatively
      limited understanding of the host characteristics of this disease; consequently,
      further research is necessary. In this study, we examined the humoral immune
      response in 43 Georgian individuals that had been diagnosed with brucellosis 3-12
      months before enrollment in the study, many of whom still had symptoms after the
      completion of antibiotic therapy. In total, 35 of 43 (83%) of the patients had
      antibodies that bound to Brucella lipopolysaccharide (LPS) by COMPELISA, and 34
      of 38 (89%) patients had demonstrable specific antibodies to BrucellergeneTM
      antigens; the results from the two ELISAs were highly correlated (p=0.031,
      r=0.851). We also studied the cellular immune responses in 15 patients. All of
      the patients generated interferon (IFN)-gamma in response to ex vivo stimulation
      with Brucella protein antigens, and the majority of the patients maintained
      measurable humoral responses to both LPS and protein antigens. From this initial
      study, we conclude that measurement of antibody and of cellular (IFN-gamma)
      responses to brucellergene OCB protein epitopes may be worthy of further
      investigation as an alternative or adjunct to current diagnostics.

PMID- 23164561
TI  - A 2010 Austrian Salmonella enteritidis PT4 outbreak associated with a laying hen
      holding previously involved in an S. enteritidis PT4 cluster: pitfalls of
      regulatory responses in risk management.
AB  - We report on an outbreak caused by Salmonella enteritidis phage type 4 (PT4)
      among 143 participants at a soccer camp in Austria in August 2010. The outbreak
      affected 34 persons, including 24 epidemiologically related cases and 10
      laboratory-confirmed cases. Food-specific cohort analyses revealed spaetzle
      (homemade noodles) (relative risks (RR): 2.68; 95% CI: 1.13-6.45), hamburger (RR:
      2.70; 95% CI: 1.13-6.45) and potato salad (RR: 2.91; 95% CI: 1.69-5.02) as the
      most biologically plausible infection sources. Eggs used as ingredients were
      considered to be the vehicle of infection for the outbreak strain. The sole egg
      producer supplying the hotel that housed the soccer camp participants with table
      eggs operated two flocks. One flock had been epidemiologically and
      microbiologically related to a previous S. enteritidis PT4 outbreak affecting the
      same Austrian province in the four months preceding the August outbreak. We
      hypothesize that eggs from this flock, already condemned for industrial use only,
      were falsely declared table eggs and sold among eggs from the non-banned flock
      causing the subsequent outbreak. In Austria, the illegal distribution of eggs
      designated for industrial use (i.e., false declaration of these eggs as table
      eggs) has been previously documented. Our findings underscore the potential of
      proper epidemiological outbreak investigation to identify the pitfalls of
      regulatory responses in risk management.

PMID- 23164562
TI  - Tuberculosis treatment default in a large tertiary care hospital in urban
      Nigeria: prevalence, trend, timing and predictors.
AB  - OBJECTIVES: Few studies have investigated tuberculosis treatment default in
      tertiary care settings. We aimed to determine the prevalence, trend, timing and
      predictors of defaulting from tuberculosis treatment in a Nigerian tertiary
      hospital. METHODS: Data entered from 2006 to 2010 in the Federal Medical Centre,
      Abakaliki, tuberculosis treatment register were sorted into six treatment
      outcomes. Five outcomes were combined into one variable called 'non-defaulters'
      and were compared with "defaulters". The statistical analysis was conducted using
      SPSS. RESULTS: Of 671 tuberculosis patients, 192 (28.6%) defaulted. Of these, 126
      (66%) were >=30 years old, and 115 (60%) had pulmonary tuberculosis. Furthermore,
      106 (55%) were males, and 125 (65%) lived in a rural area. The annual proportion
      of defaulters dropped from 34.8% to 20.6%, but the decreasing trend was not
      statistically significant (P=0.132 for trend). Of the defaulters, 148 (77.1%)
      defaulted during their intensive phase of treatment. The median default time was
      7 (IQR 5-8) weeks. The independent predictors of treatment default were older age
      (aOR 1.5), rural residence (aOR 2.3), and HIV seropositivity (aOR, 2.8).
      CONCLUSION: TB treatment default is high and must be reduced. This may be
      achieved through improved rural DOT, further patient education, and enhanced
      coordination of TB/HIV care.

PMID- 23164563
TI  - An assessment of the emergency response among health workers involved in the 2010
      cholera outbreak in northern Nigeria.
AB  - BACKGROUND: The 2010 cholera outbreak in northern Nigeria affected over 40,000
      people, with a case fatality rate (CFR) of >=3.75%. We assessed the emergency
      response of health care workers (HCWs) involved in case management. METHOD: This
      was a cross-sectional study with data collected through a self-administered
      questionnaire. Data entry and analysis were performed using Epi info software.
      RESULTS: A total of 56 HCWs were interviewed. The mean age was 31 years (SD+/
      8.16 years). The majority of the HCWs (80%; n=45) were aged 18-39 years. Most
      were community health extension workers (60%), and 3.6% (n=2) were medical
      doctors. Many of the HCWs had less than 2 years of work experience (42%).
      Additionally, 82% of the respondents had <1 week of cholera emergency response
      training, and 50% of the HCWs managed >20 suspected cases of cholera per day.
      Although 78% of HCWs reported the practice of universal safety precautions, 32%
      (n=18) knew HCWs who developed symptoms of cholera during the epidemic, most of
      which was believed to be hospital acquired (78%). We also found that 77% (n=43)
      of HCWs had no access to the required emergency response supplies. CONCLUSION:
      Inadequate training, a lack of qualified HCWs and a limited supply of emergency
      response kits were reported. Therefore, the government and stakeholders should
      address the gaps noted to adequately control and prevent future epidemics.

PMID- 23164564
TI  - Burden of pneumococcal infection in adults in Colombia.
AB  - INTRODUCTION: The burden of Streptococcus pneumoniae infections is highest in
      children. Estimates in adult population are uncommon. We determined the burden of
      disease associated with pneumococcus in adults in Colombia in year 2008.
      METHODOLOGY: Using different data sources (official mortality records, medical
      databases, published literature and local epidemiological data) we estimated
      prevalence, incidence, mortality and disability due to bacterial pneumonia,
      bacterial meningitis and bacteremia of any cause for year 2008, and the fraction
      of these that can be attributed to S. pneumoniae. RESULTS: A total of 63,463
      DALYs are lost due to S. pneumoniae in Colombians age 15 or over. Most of this
      burden (51,848 DALYs, 81.7%) is due to pneumonia, followed by meningitis (9241
      DALYs, 14.6%). The three conditions, overall, represent 2.03 DALYs per 1000
      Colombians in that age range. CONCLUSIONS: Despite the lower incidence of
      pneumococcal disease in adults, as compared with children, its burden is still
      significant, comparable to that of schizophrenia or epilepsy. This study may
      provide a benchmark for future preventive interventions.

PMID- 23164565
TI  - Diabetic status of patients with leprosy in Kuwait.
AB  - OBJECTIVE: The aim of this study was to screen for diabetes mellitus in leprosy
      patients to elucidate whether leprosy infection may play a role in the
      pathogenesis of diabetes mellitus in this population. SUBJECTS AND METHODS:
      Thirty patients of different ages and of both sexes with various types of leprosy
      were included in this study. In addition, 15 healthy individuals of comparable
      age and sex who had no family history of diabetes mellitus were identified as
      controls. In both groups, determinations of fasting and postprandial blood sugar,
      an oral glucose tolerance test (OGTT), measures of fasting serum insulin and pro
      inflammatory cytokine tumor necrosis factor alpha (TNFalpha), as well as
      calculations using the Homeostasis Model Assessment for Insulin Resistance (HOMA
      IR), were carried out. RESULT: Approximately 13.3% of the leprosy patients were
      diabetic, and 37.7% were in pre-diabetic. The highest incidences of diabetes and
      pre-diabetes were in lepromatous leprosy (10% and 20%, respectively); a lower
      incidence of pre-diabetes (6.6%) was observed in tuberculoid leprosy; and the
      lowest incidence of diabetes (0.0%) was noted in borderline leprosy patients.
      Although normal healthy persons were not diabetic (0%), 20% were pre-diabetic.
      CONCLUSION: This study revealed that the incidence of diabetes was higher in the
      leprosy patients than in the control group. As a result, we recommend that all
      leprosy patients should be screened for diabetes.

PMID- 23164566
TI  - Unsafe injection procedures and staff training.

PMID- 23164567
TI  - Brief psychotherapy for demoralization in terminal cancer: a case report.

PMID- 23164568
TI  - Direct molecular evolution of detergent-stable G protein-coupled receptors using
      polymer encapsulated cells.
AB  - G protein-coupled receptors (GPCRs) are the largest class of pharmaceutical
      protein targets, yet drug development is encumbered by a lack of information
      about their molecular structure and conformational dynamics. Most mechanistic and
      structural studies as well as in vitro drug screening with purified receptors
      require detergent solubilization of the GPCR, but typically, these proteins
      exhibit only low stability in detergent micelles. We have developed the first
      directed evolution method that allows the direct selection of GPCRs stable in a
      chosen detergent from libraries containing over 100 million individual variants.
      The crucial concept was to encapsulate single Escherichia coli cells of a
      library, each expressing a different GPCR variant, to form detergent-resistant,
      semipermeable nano-containers. Unlike naked cells, these containers are not
      dissolved by detergents, allowing us to solubilize the GPCR proteins in situ
      while maintaining an association with the protein's genetic information, a
      prerequisite for directed evolution. The pore size was controlled to permit GPCR
      ligands to permeate but the solubilized receptor to remain within the
      nanocapsules. Fluorescently labeled ligands were used to bind to those GPCR
      variants inside the nano-containers that remained active in the detergent tested.
      With the use of fluorescence-activated cell sorting, detergent-stable mutants
      derived from two different family A GPCRs could be identified, some with the
      highest stability reported in short-chain detergents. In principle, this method
      (named cellular high-throughput encapsulation, solubilization and screening) is
      not limited to engineering stabilized GPCRs but could be used to stabilize other
      proteins for biochemical and structural studies.

PMID- 23164569
TI  - A 2.1-A-resolution crystal structure of unliganded CRM1 reveals the mechanism of
      autoinhibition.
AB  - CRM1 mediates nuclear export of numerous proteins and ribonucleoproteins
      containing a leucine-rich nuclear export signal (NES). Binding of RanGTP to CRM1
      in the nucleus stabilizes cargo association with CRM1, and vice versa, but the
      mechanism underlying the positive cooperativity in RanGTP and NES binding to CRM1
      remains incompletely understood. Herein we report a 2.1-A-resolution crystal
      structure of unliganded Saccharomyces cerevisiae CRM1 (Xpo1p) that demonstrates
      that an internal loop of CRM1 (referred to as HEAT9 loop) is primarily
      responsible for maintaining the NES-binding cleft in a closed conformation,
      rendering CRM1 incapable of NES binding in the absence of RanGTP. The structure
      also shows that the C-terminal tail of CRM1 stabilizes the autoinhibitory
      conformation of the HEAT9 loop and thereby reinforces autoinhibition. Comparison
      with the structures of CRM1-NES-RanGTP complexes reveals how binding of RanGTP is
      associated with a series of allosteric conformational changes in CRM1 that lead
      to opening of the NES-binding cleft, allowing for stable binding of NES cargoes.

PMID- 23164570
TI  - When the spleen gets tough, the varices get going.

PMID- 23164571
TI  - FoxD3 is a novel, epigenetically regulated tumor suppressor in gastric
      carcinogenesis.

PMID- 23164572
TI  - Hepatitis C virus replicons volume 3 and 4.

PMID- 23164573
TI  - Nuclear factor-kappaB in pancreatitis: Jack-of-all-trades, but which one is more
      important?

PMID- 23164574
TI  - Metabolic engineering of muconic acid production in Saccharomyces cerevisiae.
AB  - The dicarboxylic acid muconic acid has garnered significant interest due to its
      potential use as a platform chemical for the production of several valuable
      consumer bio-plastics including nylon-6,6 and polyurethane (via an adipic acid
      intermediate) and polyethylene terephthalate (PET) (via a terephthalic acid
      intermediate). Many process advantages (including lower pH levels) support the
      production of this molecule in yeast. Here, we present the first heterologous
      production of muconic acid in the yeast Saccharomyces cerevisiae. A three-step
      synthetic, composite pathway comprised of the enzymes dehydroshikimate
      dehydratase from Podospora anserina, protocatechuic acid decarboxylase from
      Enterobacter cloacae, and catechol 1,2-dioxygenase from Candida albicans was
      imported into yeast. Further genetic modifications guided by metabolic modeling
      and feedback inhibition mitigation were introduced to increase precursor
      availability. Specifically, the knockout of ARO3 and overexpression of a feedback
      resistant mutant of aro4 reduced feedback inhibition in the shikimate pathway,
      and the zwf1 deletion and over-expression of TKL1 increased flux of necessary
      precursors into the pathway. Further balancing of the heterologous enzyme levels
      led to a final titer of nearly 141mg/L muconic acid in a shake-flask culture, a
      value nearly 24-fold higher than the initial strain. Moreover, this strain has
      the highest titer and second highest yield of any reported shikimate and aromatic
      amino acid-based molecule in yeast in a simple batch condition. This work
      collectively demonstrates that yeast has the potential to be a platform for the
      bioproduction of muconic acid and suggests an area that is ripe for future
      metabolic engineering efforts.

PMID- 23164575
TI  - Genome-scale identification and characterization of ethanol tolerance genes in
      Escherichia coli.
AB  - The identification of relevant gene targets for engineering a desired trait is a
      key step in combinatorial strain engineering. Here, we applied the multi-Scalar
      Analysis of Library Enrichments (SCALEs) approach to map ethanol tolerance onto
      1,000,000 genomic-library clones in Escherichia coli. We assigned fitness scores
      to each of the ~4,300 genes in E. coli, and through follow-up confirmatory
      studies identified 9 novel genetic targets (12 genes total) that increase E. coli
      ethanol tolerance (up to 6-fold improved growth). These genetic targets are
      involved in the processes related to cell membrane composition, translation,
      serine biosynthesis, and transcription regulation. Transcriptional profiling of
      the ethanol stress response in 5 of these ethanol-tolerant clones revealed a
      total of 700 genes with significantly altered expression (mapped to 615
      significantly enriched gene ontology terms) across all five clones, with similar
      overall changes in global gene expression between two clone clusters. All ethanol
      tolerant clones analyzed shared 6% of the overexpressed genes and showed
      enrichment for transcription regulation-related GO terms. iTRAQ-based proteomic
      analysis of ethanol-tolerant strains identified upregulation of proteins related
      to ROS mitigation, fatty acid biosynthesis, and vitamin biosynthesis as compared
      to the parent strain's ethanol response. The approach we outline here will be
      useful for engineering a variety of other traits and further improvements in
      alcohol tolerance.

PMID- 23164576
TI  - In-silico-driven metabolic engineering of Pseudomonas putida for enhanced
      production of poly-hydroxyalkanoates.
AB  - Here, we present systems metabolic engineering driven by in-silico modeling to
      tailor Pseudomonas putida for synthesis of medium chain length PHAs on glucose.
      Using physiological properties of the parent wild type as constraints, elementary
      flux mode analysis of a large-scale model of the metabolism of P. putida was used
      to predict genetic targets for strain engineering. Among a set of priority ranked
      targets, glucose dehydrogenase (encoded by gcd) was predicted as most promising
      deletion target. The mutant P. putida Deltagcd, generated on basis of the
      computational design, exhibited 100% increased PHA accumulation as compared to
      the parent wild type, maintained a high specific growth rate and exhibited an
      almost unaffected gene expression profile, which excluded detrimental side
      effects of the modification. A second mutant strain, P. putida Deltapgl, that
      lacked 6-phosphogluconolactonase, exhibited a substantially decreased PHA
      synthesis, as was also predicted by the model. The production potential of P.
      putida Deltagcd was assessed in batch bioreactors. The novel strain showed an
      increase of the PHA yield (+80%), the PHA titer (+100%) and cellular PHA content
      (+50%) and revealed almost unaffected growth and diminished by-product formation.
      It was thus found superior in all relevant criteria towards industrial
      production. Beyond the contribution to more efficient PHA production processes at
      reduced costs that might replace petrochemical plastics in the future, the study
      illustrates the power of computational prediction to tailor microbial strains for
      enhanced biosynthesis of added-value compounds.

PMID- 23164577
TI  - Identification and engineering of cholesterol oxidases involved in the initial
      step of sterols catabolism in Mycobacterium neoaurum.
AB  - Mycobacteria have been modified to transform sterols to produce valuable
      steroids. Here, we demonstrated that the oxidation of sterols to sterones is a
      rate-limiting step in the catabolic pathway of sterols in Mycobacterium neoaurum.
      Two cholesterol oxidases ChoM1 and ChoM2 involved in the step were identified in
      M. neoaurum and the ChoM2 shared up to 45% identity with other cholesterol
      oxidases. We demonstrated that the combination of ChoM1 and ChoM2 plays a
      significant role in this step. Accordingly, we developed a strategy to overcome
      this rate-limiting step by augmenting the activity of cholesterol oxidases in M.
      neoaurum strains to enhance their transformation productivity of sterols to
      valuable steroids. Our results indicated that the augmentation of ChoM2 achieved
      5.57g/l androst-1,4-diene-3,17-dione in M. neoaurum NwIB-01MS and 6.85g/l androst
      4-ene-3,17-dione in M. neoaurum NwIB-R10, greatly higher than the original yield,
      3.87g/l androst-1,4-diene-3,17-dione and 4.53g/l androst-4-ene-3,17-dione,
      respectively.

PMID- 23164578
TI  - Establishing a platform cell factory through engineering of yeast acetyl-CoA
      metabolism.
AB  - Production of fuels and chemicals by industrial biotechnology requires efficient,
      safe and flexible cell factory platforms that can be used for production of a
      wide range of compounds. Here we developed a platform yeast cell factory for
      efficient provision of acetyl-CoA that serves as precursor metabolite for a wide
      range of industrially interesting products. We demonstrate that the platform cell
      factory can be used to improve the production of alpha-santalene, a plant
      sesquiterpene that can be used as a perfume by four-fold. This strain would be a
      useful tool to produce a wide range of acetyl-CoA-derived products.

PMID- 23164579
TI  - Predictive design of mRNA translation initiation region to control prokaryotic
      translation efficiency.
AB  - Precise prediction of prokaryotic translation efficiency can provide valuable
      information for optimizing bacterial host for the production of biochemical
      compounds or recombinant proteins. However, dynamic changes in mRNA folding
      throughout translation make it difficult to assess translation efficiency. Here,
      we systematically determined the universal folding regions that significantly
      affect the efficiency of translation in Escherichia coli. By assessing the
      specific regions for mRNA folding, we could construct a predictive design method,
      UTR Designer, and demonstrate that proper codon optimization around the 5'
      proximal coding sequence is necessary to achieve a broad range of expression
      levels. Finally, we applied our method to control the threshold value of input
      signals switching on a genetic circuit. This should increase our understanding of
      the processes underlying gene expression and provide an efficient design
      principle for optimizing various biological systems, thereby facilitating future
      efforts in metabolic engineering and synthetic biology.

PMID- 23164580
TI  - Recombinant strains for the enhanced production of bioengineered rapalogs.
AB  - The rapK gene required for biosynthesis of the DHCHC starter acid that initiates
      rapamycin biosynthesis was deleted from strain BIOT-3410, a derivative of
      Streptomyces rapamycinicus which had been subjected to classical strain and
      process development and capable of robust rapamycin production at titres up to
      250mg/L. The resulting strain BIOT-4010 could no longer produce rapamycin, but
      when supplied exogenously with DHCHC produced rapamycin at titres equivalent to
      its parent strain. This strain enabled mutasynthetic access to new rapalogs that
      could not readily be isolated from lower titre strains when fed DHCHC analogs.
      Mutasynthesis of some rapalogs resulted predominantly in compounds lacking late
      post polyketide synthase biosynthetic modifications. To enhance the relative
      production of fully elaborated rapalogs, genes encoding late-acting biosynthetic
      pathway enzymes which failed to act efficiently on the novel compounds were
      expressed ectopically to give strain BIOT-4110. Strains BIOT-4010 and BIOT-4110
      represent valuable tools for natural product lead optimization using biosynthetic
      medicinal chemistry and for the production of rapalogs for pre-clinical and early
      stage clinical trials.

PMID- 23164581
TI  - Factors affecting the success of endoscopic treatment of sphincterotomy bleeding.
AB  - BACKGROUND AND AIM: Endoscopic methods are effective in the control of endoscopic
      sphincterotomy (ES) bleeding. Initial failure or recurrent bleeding may develop
      in some patients, which may require angiographic or surgical interventions. We
      aimed to determine the factors leading to failure of endoscopic treatment
      methods. METHODS: Forty-six patients (1.37%) had endoscopic and/or clinically
      significant bleeding among a total of 3354 ESs (2998 primary, 356 re-ES)
      performed within 3 years. Forty-one patients (21 immediate, 20 late onset
      bleeding) underwent endoscopic treatment. Nineteen patients were treated
      initially by epinephrine injection and 22 with heat probe. The relation between
      demographic, laboratory parameters, presence of comorbidity, cholangitis,
      coagulopathy, and juxtapapillary diverticula, pre-cutting, type of ES, time and
      pattern of bleeding, treatment modality, the success and relapse of endoscopic
      treatment were evaluated. RESULTS: The first method was successful in the
      treatment of bleeding in 18 patients with heat probe and epinephrine injection,
      each. Presence of cholangitis, coagulopathy and increased international
      normalized ratio (INR) levels were found to determine the success of first
      treatment method. Bleeding could be stopped in all of the patients either with
      initially preferred or combined methods. Five patients developed recurrent
      bleeding. Presence of cholangitis, coagulopathy, increased INR levels, low
      thrombocyte counts and performance of precutting were factors predicting
      recurrence. Both of the treatment methods were 100% effective in patients without
      coagulopathy and none of the patients developed recurrent bleeding. CONCLUSIONS:
      Treatment of ES bleeding in patients with high risks such as coagulopathy require
      new effective methods. Patients with coagulopathy must be carefully followed for
      the development of recurrent bleeding.

PMID- 23164582
TI  - Roles and delivery mechanisms of fungal effectors during infection development:
      common threads and new directions.
AB  - Fungal effectors have often been referred as a 'sea of diversity', but recently,
      experiments have shed some light onto effector biology, including discovery that
      unrelated fungi utilize some common methods for creating a more compatible host
      environment. A wheat pathogen and a rice pathogen, for example, have evolved
      mechanisms to suppress chitin-mediated basal defenses in their respective plant
      hosts. Smut fungi, on the other hand, might have evolved a unique mechanism to
      manipulate their host environment by altering cell metabolism. Genome mining and
      bioinformatics pipelines have streamlined the suite of effectors in important
      pathogen genomes, so researchers can make more targeted strikes on potentially
      important effectors. This combination of informatics and empirical studies will
      allow greater insight into effector function.

PMID- 23164583
TI  - Determinants and clinical significance of flow via the fenestration in the Fontan
      pathway: a multimodality study.
AB  - BACKGROUND: The use of a fenestration in the Fontan pathway remains
      controversial, partly because its hemodynamic effects and clinical consequences
      are insufficiently understood. The objective of this study was to quantify the
      magnitude of fenestration flow and to characterize its hemodynamic consequences
      after an intermediate interval after surgery. METHODS: Twenty three patients with
      a fenestrated extracardiac conduit prospectively underwent investigation by
      cardiac magnetic resonance (CMR), echocardiography, and invasive manometry under
      the same general anesthetic 12 +/- 4 months after Fontan surgery. Fenestration
      flow was determined using phase contrast CMR by subtracting flow in the Fontan
      pathway above the fenestration from Fontan flow below the fenestration. RESULTS:
      Fenestration flow constituted a mean of 31 +/- 12% (range 8-50%) of ventricular
      preload. It was associated with a lower Qp/Qs (r = -0.64, p=0.001) and oxygen
      saturation (r = -0.74, p<0.0001). Fenestration flow volume was correlated with
      pulmonary vascular resistance (r = 0.45, p = 0.04) and markers of ventricular
      diastolic function (early diastolic strain rate r = 0.57, p = 0.008 and
      ventricular untwist rate r = 0.54, p = 0.02). In 14 patients (61%) all of the net
      inferior vena cava flow and part of the superior vena cava flow were diverted
      into the systemic atrium and did not reach the lungs. CONCLUSIONS: Fenestration
      flow can be measured accurately with CMR. In two-thirds of the patients not only
      all of the inferior vena cava flow, but also some of the superior vena cava flow
      is diverted through the fenestration. Fenestration flow is driven by a balance
      between pulmonary vascular resistance and early diastolic ventricular function.

PMID- 23164584
TI  - Catheter-based renal sympathetic denervation exerts acute and chronic effects on
      renal hemodynamics in swine.
AB  - OBJECTIVES: We investigated the acute and chronic effects of catheter-based renal
      sympathetic denervation (RSD) on renal hemodynamics assessed by average peak
      velocity (APV), renal blood flow (RBF), renal flow reserve (RFR) and resistive
      index (RI). BACKGROUND: Sympathetic overdrive is accompanied by impaired RBF,
      whereas there is no data on the effects of transcatheter RSD on renal hemodynamic
      balance. METHODS: Before and post-RSD (acutely and after 1 month), in 9 farm
      swines we measured APV by a 0.014-inch Doppler flow wire placed in the stem of
      the renal artery under baseline and hyperemic conditions, induced by intrarenal
      dopamine (50 MUg/kg). RFR was calculated as the ratio of hyperemic to basal peak
      velocity, and RI was estimated as (peak systolic velocity-end-diastolic
      velocity)/peak systolic velocity. RSD was achieved via the lumen of the main
      renal artery with a specifically designed catheter connected to a radiofrequency
      generator according to prespecified algorithm. RESULTS: APV and RBF increased
      acutely post ablation in all animals, compared to APV and RBF before ablation
      (61.44 +/- 32.6 vs 20.44 +/- 6.38 cm/s, p<0.001 and 407.4 +/- 335.1 vs 161.1 +/-
      76.6 ml/min, p=0.003; respectively), whereas RFR and RI were reduced (1.51 +/-
      0.59 vs 2.85 +/- 1.33, p<0.001 and 0.67 +/- 0.07 vs 0.74 +/- 0.07, p=0.005;
      respectively). One month post ablation APV and RBF compared to APV and RBF before
      ablation remained significantly higher whereas RFR and RI remained lower as
      compared to baseline. CONCLUSIONS: Catheter-based RSD exerts acute and chronic
      effects on renal hemodynamics in a large animal model. If confirmed in humans RBF
      parameters may be used as direct markers of successful RSD.

PMID- 23164585
TI  - Incidence and clinical outcome of prosthesis-patient mismatch after transcatheter
      aortic valve implantation with the CoreValve prosthesis.

PMID- 23164586
TI  - Reversible left ventricular apical ballooning after heavy alcohol consumption in
      a patient with hypertrophic cardiomyopathy.

PMID- 23164587
TI  - Transcatheter renal sympathetic ablation for resistant hypertension: in vivo
      insights in humans from optical coherence tomography.

PMID- 23164589
TI  - Consult for heart block in a heart transplant recipient.

PMID- 23164588
TI  - Thigh circumference and low ankle brachial index in US adults: results from the
      National Health and Nutrition Examination Survey 1999-2004.
AB  - OBJECTIVE: Recent studies have suggested that smaller thighs are a disadvantage
      for health and survival, but the association of thigh circumference with
      atherosclerosis remains uncertain. The purpose of this study was to investigate
      the association between thigh circumference and peripheral arterial disease
      (PAD), as measured by ankle brachial index (ABI). METHODS: This study used data
      from the National Health and Nutrition Examination Survey (1999-2004), in which
      participants' ABI and thigh circumference were measured simultaneously. A total
      of 5716 participants (2959 men and 2757 women) were included in the final
      analysis. A diagnosis of PAD was determined on the basis of ABI <0.9. RESULTS:
      The overall prevalence of PAD in this sample was 6.6%. Thigh circumference of
      those with PAD was 50.1cm compared to 52.2 cm for those without PAD (p < 0.0001).
      After adjusting for potential covariates, the prevalence of PAD generally
      decreased as thigh circumference increased up to 55 cm. In the first quantile
      (smallest thigh circumference), men and women had as much as a 4.8-fold (95% CI,
      2.28-10.29) and a 3-fold (95% CI, 1.45-6.18) increased risk of PAD, respectively.
      Above 55 cm, PAD was no longer related to thigh circumference. CONCLUSIONS: Small
      thigh circumference may be associated with PAD, as measured by ABI.

PMID- 23164590
TI  - Congenital valvular aortic stenosis in young adults: predictors for rate of
      progression of stenosis and aortic dilatation.
AB  - BACKGROUND: Congenital aortic stenosis (AS) is the most common obstructive left
      sided cardiac lesion in young adults, however little is known about the
      progression in adults. Therefore, we aimed to evaluate the progression rate of AS
      and aortic dilatation in a large multicenter retrospective cohort of asymptomatic
      young adults with congenital valvular AS. METHODS: Data were obtained from chart
      abstraction. Linear mixed-effects models were used to evaluate the progression of
      AS and aortic dilatation over time. A joint model combining longitudinal
      echocardiographic and survival data was used for survival analysis. RESULTS: A
      total of 414 patients (age 29 +/- 10 years, 68% male) were included. Median
      follow-up duration was 4.1 (2.5-5.1) years (1587 patient-years). Peak aortic
      velocity was 3.4 +/- 0.7 m/s at baseline and did not change over time in the
      total patient population (-0.01 +/- 0.03 m/s/year). Increased left ventricular
      mass was significantly associated with faster AS progression (p<0.001). Aortic
      dilatation was present in 34% at baseline and 48% at follow-up (p<0.001). The
      aortic diameter linearly increased over time with a rate of 0.7 +/- 0.2mm/year.
      Rate of aortic dissection was 0.06% per patient-year. Seventy patients required
      an aortic valve intervention (4.4% per patient-year), with AS progression rate as
      most powerful predictor (HR 5.11 (95% CI 3.47-7.53)). CONCLUSIONS: In the
      majority of patients with mild-to-moderate congenital AS, AS severity does not
      progress over time. However patients with left ventricular hypertrophy are at
      risk for faster progression and should be monitored carefully. Although aortic
      dissections rarely occur, aortic dilatation is common and steadily progresses
      over time, warranting serial aortic imaging.

PMID- 23164591
TI  - Five-year outcomes of surgical or percutaneous myocardial revascularization in
      diabetic patients.
AB  - BACKGROUND: The study compares five-year clinical outcomes of CABG vs PCI in a
      real world population of diabetic patients with multivessel coronary disease
      since it is not clear whether to prefer surgical or percutaneous
      revascularization. METHODS: Between July 2002 and December 2008, 2885 multivessel
      coronary diabetic patients underwent revascularization (1466 CABG and 1419 PCI)
      at hospitals in Emilia-Romagna Region, Italy and were followed for 1827 +/- 617
      days by record linkage of two clinical registries with the regional
      administrative database of hospital admissions and the mortality registry. Five
      year incidences of MACCE (mortality, acute myocardial infarction [AMI], stroke,
      and repeat revascularization [TVR]) were assessed with Kaplan-Meier estimates,
      Cox proportional hazards regression and cumulative incidence functions of death
      and TVR, to evaluate the competing risk of AMI on death and TVR. The same
      analyses were applied to the propensity score matched subgroup of patients
      undergoing CABG or PCI with DES and with complete revascularization. RESULTS: PCI
      had higher mortality for all causes (HR: 1.8, 95% CI 1.4-2.2 p<0.0001), AMI (HR:
      3.3, 95% CI 2.4-4.6 p<0.0001) and TVR (HR: 4.5, 95% CI 3.4-6.1 p<0.0001). No
      significant differences emerged for stroke (HR: 0.8, 95% CI 0.5-1.2 p=0.26). The
      higher incidence of AMI caused higher mortality in PCI group. Results did not
      change comparing CABG with PCI patients receiving complete revascularization or
      DES only. CONCLUSIONS: Diabetics show a higher incidence of MACCE with PCI than
      with CABG: thus diabetes and its degree of control should be considered when
      choosing the type of revascularization.

PMID- 23164592
TI  - Elderly patients diagnosed with idiopathic pulmonary arterial hypertension:
      results from the COMPERA registry.
AB  - BACKGROUND: Originally reported to occur predominantly in younger women,
      idiopathic pulmonary arterial hypertension (IPAH) is increasingly diagnosed in
      elderly patients. We aimed to describe the characteristics of such patients and
      their survival under clinical practice conditions. METHODS: Prospective registry
      in 28 centers in 6 European countries. Demographics, clinical characteristics,
      hemodynamics, treatment patterns and outcomes of younger (18-65 years) and
      elderly (>65 years) patients with newly diagnosed IPAH (incident cases only) were
      compared. RESULTS: A total of 587 patients were eligible for analysis. The median
      (interquartile, [IQR]) age at diagnosis was 71 (16) years. Younger patients
      (n=209; median age, 54 [16] years) showed a female-to-male ratio of 2.3:1 whereas
      the gender ratio in elderly patients (n=378; median age, 75 [8] years) was almost
      even (1.2:1). Combinations of PAH drugs were widely used in both populations,
      albeit less frequently in older patients. Elderly patients were less likely to
      reach current treatment targets (6 min walking distance>400 m, functional class I
      or II). The survival rates 1, 2, and 3 years after the diagnosis of IPAH were
      lower in elderly patients, even when adjusted for age- and gender-matched
      survival tables of the general population (p=0.006 by log-rank analysis).
      CONCLUSIONS: In countries with an aging population, IPAH is now frequently
      diagnosed in elderly patients. Compared to younger patients, elderly patients
      present with a balanced gender ratio and different clinical features, respond
      less well to medical therapy and have a higher age-adjusted mortality. Further
      characterization of these patients is required. CLINICAL TRIALS REGISTRATION:
      NCT01347216.

PMID- 23164593
TI  - Intravascular ultrasound assessed incomplete stent apposition and stent fracture
      in stent thrombosis after bare metal versus drug-eluting stent treatment the
      Nordic Intravascular Ultrasound Study (NIVUS).
AB  - BACKGROUND: This prospective multicenter registry used intravascular ultrasound
      (IVUS) in patients with definite stent thrombosis (ST) to compare rates of
      incomplete stent apposition (ISA), stent fracture and stent expansion in patients
      treated with drug-eluting (DES) versus bare metal (BMS) stents. ST is a rare, but
      potential life threatening event after coronary stent implantation. The etiology
      seems to be multifactorial. METHODS: 124 patients with definite ST were assessed
      by IVUS during the acute ST event. The study was conducted in 15 high-volume
      percutaneous coronary intervention -centers in the Nordic-Baltic countries.
      RESULTS: In early or late ST there were no differences in ISA between DES and
      BMS. In very late ST, ISA was a more frequent finding in DES than in BMS (52%
      vs.16%; p=0.005) and the maximum ISA area was larger in DES compared to BMS (1.1
      +/- 2.3mm(2) vs. 0.1 +/- 0.5mm(2); p=0.004). Further, ISA was more prevalent in
      sirolimus-eluting than in paclitaxel-eluting stents (58% vs. 37%; p=0.02). Stent
      fractures were found both in DES (16%) and BMS (24%); p=0.28, and not related to
      time of stent thrombosis occurrence. For stents with nominal diameters >= 2.75
      mm, 38% of the DES and 22% of the BMS had a minimum stent area of less than
      5mm(2); p=0.14. CONCLUSIONS: Very late stent thrombosis was more prevalent and
      associated with more extensive ISA in DES than in BMS treated patients. Stent
      fracture was a common finding in ST after DES and BMS implantation.

PMID- 23164594
TI  - Acute kidney injury following transcatheter aortic valve implantation: incidence,
      predictors and clinical outcome.
AB  - BACKGROUND: Limited data exist on renal complications of transcatheter aortic
      valve implantation (TAVI) within a comprehensive program using different valves
      with transfemoral, transapical, and trans-subclavian approach. METHODS:
      Prospective single-center registry of 102 consecutive patients undergoing TAVI
      using both approved bioprostheses and different access routes. The main objective
      was to assess the incidence, predictors and the clinical impact of acute kidney
      injury (AKI). AKI was defined according to the valve academic research consortium
      (VARC) indications. RESULTS: Mean age was 83.7 +/- 5.3 years, logistic EuroSCORE
      22.6 +/- 12.4%, and STS score 8.2 +/- 4.1%. Chronic kidney disease at baseline
      was present in 87.3%. Periprocedural AKI developed in 42 patients (41.7%): 32.4%
      stage 1, 4.9% stage 2 and 3.9% stage 3. The incidence of AKI was 66.7% in
      transapical, 30.3% in transfemoral, and 50% in trans-subclavian procedures. The
      only independent predictor of AKI was transapical access, with a hazard ratio
      (HR) between 4.57 and 5.18 based on the model used. Cumulative 1-year survival
      was 88.2%. At Cox regression analysis, the only independent predictor of 30-day
      mortality was diabetes mellitus (HR 7.05, 95% CI 1.07-46.32; p=0.042), whilst the
      independent predictors of 1-year death were baseline glomerular filtration
      rate<30 mL/min (HR 5.74, 95% CI 1.42-23.26; p=0.014) and post-procedural AKI 3
      (HR 8.59, 95% CI 1.61-45.86, p=0.012). CONCLUSIONS: TAVI is associated with a
      high incidence of AKI. Although in the majority of the cases AKI is of mild
      entity and reversible, AKI 3 holds a strong negative impact on 1-year survival.
      The incidence of AKI is higher with transapical access.

PMID- 23164595
TI  - Cardiomyopathies and congenital heart diseases in Shwachman-Diamond syndrome: a
      national survey.

PMID- 23164596
TI  - Takotsubo cardiomyopathy versus ST-elevation myocardial infarction in a large
      case-control study: proposing a new mechanism.

PMID- 23164597
TI  - Comparisons of detailed arterial healing response at seven months following
      implantation of an everolimus- or sirolimus-eluting stent in patients with ST
      segment elevation myocardial infarction.
AB  - BACKGROUND: The difference of arterial healing response following everolimus
      eluting stent (EES) or sirolimus-eluting stent (SES) implantation in patients
      with ST-segment elevated myocardial infarction (STEMI) has not been compared in
      detail. METHODS: Thirty-five patients with STEMI were randomly implanted with an
      EES or SES (23 EES, 12 SES). At seven months, neointimal thickness (NIT) and
      strut malapposition were evaluated by optical coherence tomography (OCT) and the
      grade and heterogeneity of neointimal coverage (NIC) and development of intra
      stent thrombi were evaluated by angioscopy. RESULTS: No significant differences
      were noted in clinical events experienced by the two groups, although one patient
      with an EES died following a papillary muscle rupture and one patient with a SES
      experienced sub-acute stent thrombosis. On OCT, although the EES implants showed
      a greater NIT than the SES implants (94.8 +/- 88.8 MUm vs 65.6 +/- 63.3 MUm,
      P<0.0001), both the EES and SES showed an excellent suppression of neointimal
      proliferation in the culprit lesion of STEMI. The frequency of uncovered and
      malapposed struts of EES was significantly lower than that of SES (2.7% vs.
      15.7%, P<0.0001, 0.7% vs. 2.3%, P<0.0001, respectively). The ratio of stents
      fully covered with neointima of EES group was significantly higher than that of
      SES group (P=0.04). Angioscopic analysis also showed greater dominant NIC grade
      with homogenous NIC in EES than in SES (P=0.03, P=0.0002, respectively). The
      incidence of massive intra-stent thrombus of EES was lower than that of SES
      (P=0.05). CONCLUSION: For patients with STEMI, EES may promote better arterial
      healing response than SES.

PMID- 23164598
TI  - people who inject drugs, HIV risk, and HIV testing uptake in sub-Saharan Africa.
AB  - Dramatic rises in injection drug use (IDU) in sub-Saharan Africa account for
      increasingly more infections in a region already overwhelmed by the HIV epidemic.
      There is no known estimate of the number of people who inject drugs (PWID) in the
      region, or the associated HIV prevalence in PWID. We reviewed literature with the
      goal of describing high-risk practices and exposures in PWID in sub-Saharan
      Africa, as well as current HIV prevention activities aimed at drug use. The
      literature search looked for articles related to HIV risk, injection drug users,
      stigma, and HIV testing in sub-Saharan Africa. This review found evidence
      demonstrating high rates of HIV in IDU populations in sub-Saharan Africa, high
      risk behaviors of the populations, lack of knowledge regarding HIV, and low HIV
      testing uptake. There is an urgent need for action to address IDU in order to
      maintain recent decreases in the spread of HIV in sub-Saharan Africa. 

PMID- 23164600
TI  - Science denial: a guide for scientists.
AB  - Evolution, climate change, and vaccination: in these cases and more, scientists,
      policymakers, and educators are confronted by organized campaigns to spread
      doubt, denial, and rejection of the scientific community's consensus on central
      scientific principles. To overcome these threats, scientists not only need to
      spread scientific knowledge, but must also address the social drivers of science
      denial.

PMID- 23164599
TI  - Derivation of endothelial cells from human embryonic stem cells in fully defined
      medium enables identification of lysophosphatidic acid and platelet activating
      factor as regulators of eNOS localization.
AB  - The limited availability of human vascular endothelial cells (ECs) hampers
      research into EC function whilst the lack of precisely defined culture conditions
      for this cell type presents problems for addressing basic questions surrounding
      EC physiology. We aimed to generate endothelial progenitors from human
      pluripotent stem cells to facilitate the study of human EC physiology, using a
      defined serum-free protocol. Human embryonic stem cells (hESC-ECs) differentiated
      under serum-free conditions generated CD34(+)KDR(+) endothelial progenitor cells
      after 6days that could be further expanded in the presence of vascular
      endothelial growth factor (VEGF). The resultant EC population expressed CD31 and
      TIE2/TEK, took up acetylated low-density lipoprotein (LDL) and up-regulated
      expression of ICAM-1, PAI-1 and ET-1 following treatment with TNFalpha.
      Immunofluorescence studies indicated that a key mediator of vascular tone,
      endothelial nitric oxide synthase (eNOS), was localised to a perinuclear
      compartment of hESC-ECs, in contrast with the pan-cellular distribution of this
      enzyme within human umbilical vein ECs (HUVECs). Further investigation revealed
      that that the serum-associated lipids, lysophosphatidic acid (LPA) and platelet
      activating factor (PAF), were the key molecules that affected eNOS localisation
      in hESC-ECs cultures. These studies illustrate the feasibility of EC generation
      from hESCs and the utility of these cells for investigating environmental cues
      that impact on EC phenotype. We have demonstrated a hitherto unrecognized role
      for LPA and PAF in the regulation of eNOS subcellular localization.

PMID- 23164601
TI  - The prognosis of periprocedural myocardial infarction after percutaneous coronary
      interventions.
AB  - An increase of biomarkers of myocardial necrosis is observed frequently after
      percutaneous coronary interventions (PCI) even when the procedure seems
      angiographically successful and otherwise uncomplicated. The recently updated
      Universal Definition of Myocardial infarction (MI) arbitrarily defined
      periprocedural MI (type 4a) by elevation of cardiac troponin (cTn) values >5 *
      the upper reference limit (URL) in patients with normal baseline values or a rise
      of cTn values >20% if the baseline values are elevated, together with either
      angina or new ECG changes or angiographic loss of patency of a coronary artery or
      a side branch or persistent slow or no-flow or embolization, or imaging
      demonstration of new loss of viable myocardium. Most frequent causes of such
      event are side-branch closure and/or plaque microembolization. The present review
      is focused on the prognostic implication of periprocedural necrosis. The risk
      related to a PCI-induced MI is significantly lower as compared to a spontaneous
      event where a similar increase of biomarkers is detected. Moreover, although an
      association between CK-MB elevations and adverse prognosis after PCI has been
      documented, existing data do not support the statement that an isolated elevation
      of troponins after PCI is associated with an adverse prognosis after PCI;
      increased troponin levels before PCI seem far more predictive of future events
      than a peri-procedural itself. Caution should be paid in the interpretation of
      clinical trials using type 4a MI as a primary endpoint. Nevertheless, patients
      with periprocedural myocardial damage should be treated as a higher-risk cohort,
      carefully monitored and receive an intensified secondary prevention program.

PMID- 23164602
TI  - A new ganoderic acid from Ganoderma lucidum mycelia and its stability.
AB  - A new ganoderic acid (GA), 3alpha,22beta-diacetoxy-7alpha-hydroxyl-5alpha-lanost
      8,24E-dien-26-oic acid (1), together with four known compounds GA-Mk (2), -Mc
      (3), -S (4) and -Mf (5), was isolated and characterized from Ganoderma lucidum
      mycelia. The structure of compound 1 was elucidated on the basis of
      interpretation of extensive spectroscopic data (HRMS, IR, UV, 1D and 2D NMR). Due
      to its apparent degradation during preparation procedures, the stability of
      compound 1 was assessed in several solvents in a short-term study that
      demonstrated the optimal stability in aproptic environment. A possible mechanism
      of acid-catalyzed degradation of compound 1 in methanol was proposed, consisting
      of a fast protonation, followed by a committed step of hydroxyl group removal. In
      addition, all isolated compounds were tested in vitro for their cytotoxic
      activities against 95D and HeLa tumor cell lines, with IC(50) values ranging
      from14.7 to 38.5MUM. The results may improve the understanding of chemical
      stability of GAs and provide valuable information on their separation, analysis
      and application.

PMID- 23164603
TI  - Anti-HBV agents derived from botanical origin.
AB  - There are 350,000 hepatitis B virus (HBV) carriers all over the world. Chronic
      HBV infection is at a high risk of developing liver cirrhosis and hepatocelluar
      carcinoma (HCC), and heavily threatened people's health. Two kinds of drugs
      approved by FDA for anti-HBV therapy are immunomodulators (interferon alpha,
      pegylated-interferon alpha) and nucleos(t)ide analogues (lamivudine, adefovir
      dipivoxil, entecavir, telbivudine, and tenofovir disoproxil fumarate). These
      drugs have been proved to be far from being satisfactory due to their low
      specificity, side effects, and high rate of drug resistance. There is an urgent
      need to discover and develop novel effective anti-HBV drugs. With vast resources,
      various structures, diverse biological activities and action mechanisms, as well
      as abundant clinical experiences, botanical agents become a promising source of
      finding new anti-HBV drugs. This review summarizes the recent research and
      development of anti-HBV agents derived from botanical origin on their sources and
      active components, inhibitory effects and possible toxicities, as well as action
      targets and mechanisms, and also addresses the advantages and the existing
      shortcomings in the development of botanical inhibitors. This information may not
      only broaden the knowledge of anti-HBV therapy, and offer possible alternative or
      substitutive drugs for CHB patients, but also provides considerable information
      for developing new safe and effective anti-HBV drugs.

PMID- 23164604
TI  - Sasanquasaponin from Camellia oleifera Abel. induces cell cycle arrest and
      apoptosis in human breast cancer MCF-7 cells.
AB  - Sasanquasaponin (SQS) is a triterpenoid extracted from the Chinese medicinal
      plant Camellia oleifera Abel. Little knowledge about the role of SQS in the
      prevention and treatment of cancer is available. Recent studies have shown that
      SQS possesses potent anti-tumor activities in human leukemia Jurkat cells and
      human hepatoma HepG2 cells. However, research on the effects and mechanisms of
      SQS on the treatment of breast cancer, a major cause of mortality in women
      worldwide, is not available. In this work, the effects of SQS on cell growth
      characteristics, including proliferation, cell cycle progression, and apoptosis,
      in MCF-7 cells were investigated. SQS reduced the viability of MCF-7 cells,
      induced G1 phase arrest in the cell cycle, and triggered the apoptosis of MCF-7
      cells. Stimulation of MCF-7 with SQS induced upregulation of p21 and
      downregulation of cyclin D1, which can cause G1 cell cycle arrest. Stimulation
      also induced activation of E2F1 and downregulation of p53, indicating that SQS
      induces cell cycle arrest and apoptosis via a p53-independent pathway; p53
      independent apoptosis may be mediated by E2F1 activation. Our results demonstrate
      the potential application of SQS as an anti-breast cancer agent.

PMID- 23164605
TI  - Crystal structure of the human IgG4 C(H)3 dimer reveals the role of Arg409 in the
      mechanism of Fab-arm exchange.
AB  - Antibodies of the human IgG4 subclass uniquely undergo a process of Fab-arm
      exchange in which the heavy-chains of antibodies of different specificities can
      dissociate and then recombine. The mechanism by which the resulting functionally
      monovalent but bi-specific antibodies are formed is not only key to understanding
      their biological role, but is also important for the design of therapeutic
      monoclonal antibodies. Both the hinge region and the C(H)3 domain interface are
      known to be involved, and of the residues that differ between human IgG1 and IgG4
      in C(H)3, residue 409, the only difference at the interface itself, has been
      implicated. We report the high resolution (1.8A) structure of the C(H)3 domain
      dimer of IgG4, and find that Arg409 in IgG4, when compared with Lys409 observed
      in high resolution IgG1 structures, disrupts a network of water-mediated hydrogen
      bonding that is conserved in IgG1. Other conformational differences were detected
      that are a consequence of the presence of Arg409, such as a widening of the
      separation between residues Asn390 in one domain and Ser 400 in the other, which
      opens up a groove at the edge of the interface in IgG4 compared with IgG1. The
      effect of all these differences on the C(H)3 interface, doubled as a result of
      the interface's two-fold symmetry, is weakening of the inter-domain interaction
      in IgG4 compared with IgG1. This suggests a mechanism by which Arg409 weakens the
      C(H)3 interface in IgG4, predisposing this human antibody subclass to Fab-arm
      exchange.

PMID- 23164606
TI  - Differences in readmissions after open repair versus endovascular aneurysm
      repair.
AB  - OBJECTIVE: Reintervention rates after repair of abdominal aortic aneurysm (AAA)
      are higher for endovascular repair (EVAR) than for open repair, mostly due to
      treatment for endoleaks, whereas open surgical operations for bowel obstruction
      and abdominal hernias are higher after open repair. However, readmission rates
      after EVAR or open repair for nonoperative conditions and complications that do
      not require an intervention are not well documented. We sought to determine
      reasons for all-cause readmissions within the first year after open repair and
      EVAR. METHODS: Patients who underwent elective AAA repair in California during a
      6-year period were identified from the Health Care and Utilization Project State
      Inpatient Database. All patients who had a readmission in California <=1 year of
      their index procedure were included for evaluation. Readmission rates and primary
      and secondary diagnoses associated with each readmission were analyzed and
      recorded. RESULTS: From 2003 to 2008, there were 15,736 operations for elective
      AAA repair, comprising 9356 EVARs (60%) and 6380 open repairs (40%). At 1 year
      postoperatively, the readmission rate was 52.1% after open repair and 55.4% after
      EVAR (P=.0003). The three most common principle diagnoses associated with
      readmission after any type of AAA repair were failure to thrive, cardiac issues,
      and infection. When stratified by repair type, patients who underwent open repair
      were more likely to be readmitted with primary diagnoses associated with failure
      to thrive, cardiac complications, and infection compared with EVAR (all P<.001).
      Those who underwent EVAR were more likely, however, to be readmitted with primary
      diagnoses of device-related complications (P=.05), cardiac complications, and
      infection. CONCLUSIONS: Total readmission rates within 1 year after elective AAA
      repair are greater after EVAR than after open repair. Reasons for readmission
      vary between the two cohorts but are related to the magnitude of open surgery
      after open repair, device issues after EVAR, and the usual cardiac and infectious
      complications after either intervention. Systems-based analysis of these causes
      of readmission can potentially improve patient expectations and care after
      elective aneurysm repair.

PMID- 23164607
TI  - Dissociative semantic breakdown in Alzheimer's disease: evidence from multiple
      category fluency test.
AB  - BACKGROUND: Category-specific semantic dissociation particularly in terms of
      biological and non-biological dichotomy has been described in Alzheimer's disease
      (AD). We re-examine above finding by performing multiple superordinate category
      verbal fluency test in AD patients. METHOD: We analyze the baseline
      neuropsychological assessment performance of food and animal fluency test of AD
      patients from a tertiary hospital that collected prospectively over 5 years
      period and correlation was calculated by Kappa test. The analysis is stratified
      according to literacy level (primary: 0-6 years education and secondary: >6 years
      education) and disease severity (MMSE score: mild 19-24, moderate 13-18 and
      severe <13). RESULT: A total of 296 AD patients were analyzed and only fair to
      moderate agreement between food and animal category fluency test was found
      especially in the mild AD cases (primary: kappa 0.42; secondary: kappa 0.40).
      Kappa agreement level increases when disease progress especially in the secondary
      education group. Food category, which is a more relevant semantic knowledge to
      Singapore population, is generally more affected. Higher educated subjects
      appeared to have less semantic dissociation effect when disease progress.
      CONCLUSION: Despite less primed in daily life, biological category of semantic
      knowledge appears to be affected less during AD process in highly urbanized
      Singapore society. Brain appears to have special protective mechanism towards
      living things. However, education level seems have a modulation effect towards
      the biological protective mechanism.

PMID- 23164608
TI  - Localization of centromeric breaks in head and neck squamous cell carcinoma.
AB  - Head and neck squamous cell carcinoma (HNSCC) have very complex karyotypes that
      show all types of structural rearrangements. The most frequent aberrations are
      whole-arm translocations, which appear to have their breakpoints in centromeric
      or pericentromeric regions. We aimed to pinpoint the exact location of the
      breakpoints of these marker chromosomes with high-resolution cytogenetic and
      genetic analyses using microarray comparative genomic hybridization (CGH),
      multiplex ligation-dependent probe amplification (MLPA), and fiber fluorescence
      in situ hybridization (FISH). Among the seven cell lines in this study, six (84%)
      harbored one or more centromeric breakpoints or whole-arm translocations. In
      total, microarray CGH identified 163 breakpoints, 47 (29%) of which were in
      centromeric regions. Microarray CGH and MLPA results indicated that the
      translocation breakpoints were localized between the microarray oligonucleotide
      clones and MLPA probes closest to the centromere. High-resolution fiber-FISH
      revealed adjacent or minimally overlapping signals of probes that recognize the
      pericentromeric sequences of the two participating chromosomes. This indicates
      that whole chromosome arm translocation breakpoints occur within the
      pericentromeric chromatin and not the centromere core sequences.

PMID- 23164609
TI  - Whole genome sequencing in the prevention and control of Staphylococcus aureus
      infection.
AB  - BACKGROUND: Staphylococcus aureus remains a leading cause of hospital-acquired
      infection but weaknesses inherent in currently available typing methods impede
      effective infection prevention and control. The high resolution offered by whole
      genome sequencing has the potential to revolutionise our understanding and
      management of S. aureus infection. AIM: To outline the practicalities of whole
      genome sequencing and discuss how it might shape future infection control
      practice. METHODS: We review conventional typing methods and compare these with
      the potential offered by whole genome sequencing. FINDINGS: In contrast with
      conventional methods, whole genome sequencing discriminates down to single
      nucleotide differences and allows accurate characterisation of transmission
      events and outbreaks and additionally provides information about the genetic
      basis of phenotypic characteristics, including antibiotic susceptibility and
      virulence. However, translating its potential into routine practice will depend
      on affordability, acceptable turnaround times and on creating a reliable
      standardised bioinformatic infrastructure. CONCLUSION: Whole genome sequencing
      has the potential to provide a universal test that facilitates outbreak
      investigation, enables the detection of emerging strains and predicts their
      clinical importance.

PMID- 23164610
TI  - Chlamydia pneumoniae modulates human monocyte-derived dendritic cells functions
      driving the induction of a Type 1/Type 17 inflammatory response.
AB  - Chlamydia pneumoniae is a respiratory pathogen involved in the onset of chronic
      inflammatory pathologies. Dendritic cells (DC), are major players in spreading of
      C. pneumoniae from the lungs, a crucial step leading to disseminated infections.
      Less is known concerning modulation of DC functions consequent to encounter with
      the bacterium. In order to address this aspect, human monocyte-derived (MD)DC
      were infected with C. pneumoniae. After internalization bacterial counts
      increased in MDDC, as well as the expression of CPn1046, a gene involved in
      bacterial metabolism, with a peak 48 h after the infection. Infected MDDC
      switched to the mature stage, produced IL-12p70, IL-1beta, IL-6, and IL-10, and
      drove a mixed Type 1/Type 17 polarization. Intracellular pathways triggered by C.
      pneumoniae involved Toll-like receptor (TLR) 2. Indeed, TLR2 was activated by C.
      pneumoniae in transfected HEK 293 cells, and C. pneumoniae-mediated
      phosphorylation of ERK1/2 was inhibited by an anti-TLR2 antibody in MDDC. When an
      ERK1/2 inhibitor was used, IL-12p70 and IL-10 release by MDDC was reduced and T
      cell polarization shifted towards a Type 2 profile. Overall, our findings
      unveiled the role played by TLR2 and ERK1/2 induced by C. pneumoniae to affect DC
      functions in a way that contributes to a Type 1/Type 17 pro-inflammatory
      response.

PMID- 23164611
TI  - Study on clinical epidemiology of male HIV/AIDS patients in a tertiary Chinese
      hospital, Shanghai, China.

PMID- 23164612
TI  - Pulmonary tuberculosis and lung cancer mortality in a historical cohort of
      workers with asbestosis.
AB  - OBJECTIVES: To examine pulmonary tuberculosis (PTB) infection and lung cancer
      mortality among workers with asbestosis in Hong Kong. STUDY DESIGN: Historical
      cohort study. METHODS: All 124 male incident cases of asbestosis registered at
      the Pneumoconiosis Clinic of the Tuberculosis and Chest Service of the Department
      of Health between 1981 and 2008 were recruited and followed-up until 2008 to
      ascertain vital status and underlying causes of death. Standardized mortality
      ratios (SMRs) were calculated using the person-year method. Axelson's indirect
      method was used to adjust for the potential confounding effect of cigarette
      smoking. RESULTS: Forty-five patients (36.29%) had a history of PTB at the time
      of asbestosis diagnosis. The SMR of lung cancer was 5.22 [95% confidence interval
      (CI) 1.08-15.25] for subjects with a history of PTB, and this was reduced to 2.35
      (95% CI 0.49-6.85) after indirect adjustment for smoking. Among asbestosis
      workers without a history of PTB, the SMR after indirect adjustment for smoking
      was 4.25 (95% CI 1.55-9.25) and 5.92 (95% CI 1.92-13.79) for those with
      comorbidities and those without comorbidities, respectively. Compared with other
      workers, those with a history of PTB had the highest all-cause SMR (6.73, 95% CI
      4.55-9.63) and very high mortality due to heart diseases. CONCLUSIONS: This
      historical cohort study revealed that the prevalence of PTB infection was high
      among workers with asbestosis in Hong Kong. An excess risk of lung cancer
      mortality was observed among workers with a history of PTB, but the risk was
      lower than that seen among workers without a history of PTB. These interesting
      findings need to be confirmed by future studies.

PMID- 23164613
TI  - The serotonin receptor 7 promotes neurite outgrowth via ERK and Cdk5 signaling
      pathways.
AB  - Serotonergic neurotransmission is mediated by at least 14 subtypes of 5-HT
      receptors. Among these, the CNS serotonin receptor 7 (5-HTR7) is involved in
      diverse physiological processes. Here we show that treatment of murine striatal
      and cortical neuronal cultures with 5-HTR7 agonists (8-OH-DPAT and LP-211)
      significantly enhances neurite outgrowth. This effect is abolished by the
      selective 5-HTR7 antagonist SB-269970, by the ERK inhibitor U0126, by the cyclin
      dependent kinase 5 (Cdk5) inhibitor roscovitine, as well as by cycloheximide, an
      inhibitor of protein synthesis. These data indicate that 5-HTR7 activation
      stimulates extensive neurite elongation in CNS primary cultures, subserved by ERK
      and Cdk5 activation, and de novo protein synthesis. Two-dimensional (2D) gel
      electrophoresis coupled to Western blot analyses reveals both qualitative and
      quantitative expression changes in selected cytoskeletal proteins, following
      treatment of striatal primary cultures with LP-211. In particular, the 34 kDa
      isoform of MAP1B is selectively expressed in stimulated cultures, consistent with
      a role of this protein in tubulin polymerization and neurite elongation. In
      summary, our results show that agonist-dependent activation of the endogenous 5
      HTR7 in CNS neuronal primary cultures stimulates ERK- and Cdk5-dependent neurite
      outgrowth, sustained by modifications of cytoskeletal proteins. These data
      support the hypothesis that the 5-HTR7 might play a crucial role in shaping
      neuronal morphology and behaviorally relevant neuronal networks, paving the way
      to new approaches able to modulate CNS connectivity.

PMID- 23164614
TI  - Chronic escalating cocaine exposure, abstinence/withdrawal, and chronic re
      exposure: effects on striatal dopamine and opioid systems in C57BL/6J mice.
AB  - Cocaine addiction is a chronic relapsing disease with periods of chronic
      escalating self-exposure, separated by periods of abstinence/withdrawal of
      varying duration. Few studies compare such cycles in preclinical models. This
      study models an "addiction-like cycle" in mice to determine
      neurochemical/molecular alterations that underlie the chronic, relapsing nature
      of this disease. Groups of male C57BL/6J mice received acute cocaine exposure (14
      day saline/14-day withdrawal/13-day saline + 1-day cocaine), chronic cocaine
      exposure (14 day cocaine) or chronic re-exposure (14-day cocaine/14-day
      withdrawal/14-day cocaine). Escalating-dose binge cocaine (15-30 mg/kg/injection
      * 3/day, i.p. at hourly intervals) or saline (14-day saline) was administered,
      modeling initial exposure. In "re-exposure" groups, after a 14-day injection-free
      period (modeling abstinence/withdrawal), mice that had received cocaine were re
      injected with 14-day escalating-dose binge cocaine, whereas controls received
      saline. Microdialysis was conducted on the 14th day of exposure or re-exposure to
      determine striatal dopamine content. Messenger RNA levels of preprodynorphin
      (Pdyn), dopamine D1 (Drd1) and D2 (Drd2) in the caudate putamen were determined
      by real-time PCR. Basal striatal dopamine levels were lower in mice after 14-day
      escalating exposure or re-exposure than in those in the acute cocaine group and
      controls. Pdyn mRNA levels were higher in the cocaine groups than in controls.
      Long-term adaptation was observed across the stages of this addiction-like cycle,
      in that the effects of cocaine on dopamine levels were increased after re
      exposure compared to exposure. Changes in striatal dopaminergic responses across
      chronic escalating cocaine exposure and re-exposure are a central feature of the
      neurobiology of relapsing addictive states.

PMID- 23164615
TI  - Differential modulation of retinal ganglion cell light responses by orthosteric
      and allosteric metabotropic glutamate receptor 8 compounds.
AB  - To investigate the role of mGluR8 in modulating the synaptic responses of retinal
      ganglion cells, we used a recently identified positive allosteric modulator of
      mGluR8, AZ12216052 (AZ) and the mGluR8-specific orthosteric agonist (S)-3,4
      dicarboxyphenylglycine (DCPG). These agents were applied to whole-cell voltage
      clamped ganglion cells from an isolated, superfused mouse retina preparation.
      DCPG reduced OFF-ganglion cell excitatory currents, whereas AZ enhanced the peak
      excitatory currents in ON-, OFF-, and ON-OFF-ganglion cells. The effects on
      ganglion cell inhibitory currents were more varied. The effects of the allosteric
      modulator were stronger for bright stimuli than for dim stimuli, consistent with
      receptor stimulation by endogenous glutamate being stronger during bright light
      stimulation and with mGluR8 receptors mainly being localized away from glutamate
      release sites, immuno-labeled with VGLUT1. The differential sensitivity of
      ganglion cell light responses to DCPG and AZ supports multiple sites where mGluR8
      modulates the light responses of ganglion cells.

PMID- 23164617
TI  - Ipsilateral feeding-specific circuits between the nucleus accumbens shell and the
      lateral hypothalamus: regulation by glutamate and GABA receptor subtypes.
AB  - The nucleus accumbens shell (AcbSh) and the lateral hypothalamus (LH) are both
      involved in the control of food intake. Activation of GABA(A) receptors or
      blockade of AMPA and kainate receptors within the AcbSh induces feeding, as does
      blockade of GABA(A) receptors or activation of NMDA receptors in the LH. Further,
      evidence suggests that feeding induced via the AcbSh can be suppressed by LH
      inhibition. However, it is unclear if this suppression is specific to feeding.
      Adult male Sprague-Dawley rats with 3 intracranial guide cannulas, one
      unilaterally into the AcbSh and two bilaterally into the LH, were used to explore
      this issue. DNQX (1.25 MUg) or muscimol (100 ng) infused into the AcbSh
      unilaterally elicited feeding, and this elicited intake was suppressed by
      bilateral LH injection of d-AP5 (2 MUg) or muscimol (25 ng). The effectiveness of
      d-AP5 or muscimol infusion into either the LH site ipsilateral or contralateral
      to the AcbSh injection was compared. Ipsilateral LH injection of d-AP5 or
      muscimol was significantly more effective than contralateral injection in
      suppressing food intake initiated by AcbSh injection of DNQX or muscimol. These
      results add to the prior evidence that inhibition of the LH through
      pharmacological modulation of NMDA or GABA(A) receptors specifically suppresses
      feeding initiated by AcbSh inhibition, and that these two regions communicate via
      an ipsilateral circuit to specifically regulate feeding.

PMID- 23164616
TI  - Synaptic plasticity in the hippocampus shows resistance to acute ethanol exposure
      in transgenic mice with astrocyte-targeted enhanced CCL2 expression.
AB  - It has been shown that ethanol exposure can activate astrocytes and microglia
      resulting in the production of neuroimmune factors, including the chemokine CCL2.
      The role of these neuroimmune factors in the effects of ethanol on the central
      nervous system has yet to be elucidated. To address this question, we
      investigated the effects of ethanol on synaptic transmission and plasticity in
      the hippocampus from mice that express elevated levels of CCL2 in the brain and
      their non-transgenic littermate controls. The brains of the transgenic mice
      simulate one aspect of the alcoholic brain, chronically increased levels of CCL2.
      We used extracellular field potential recordings in acutely isolated hippocampal
      slices to identify neuroadaptive changes produced by elevated levels of CCL2 and
      how these neuroadaptive changes affect the actions of acute ethanol. Results
      showed that synaptic transmission and the effects of ethanol on synaptic
      transmission were similar in the CCL2-transgenic and non-transgenic hippocampus.
      However, long-term potentiation (LTP), a cellular mechanism thought to underlie
      learning and memory, in the CCL2-transgenic hippocampus was resistant to the
      ethanol-induced depression of LTP observed in the non-transgenic hippocampus.
      Consistent with these results, ethanol pretreatment significantly impaired cued
      and contextual fear conditioning in non-transgenic mice, but had no effect in
      CCL2-transgenic mice. These data show that chronically elevated levels of CCL2 in
      the hippocampus produce neuroadaptive changes that block the depressing effects
      of ethanol on hippocampal synaptic plasticity and support the hypothesis that
      CCL2 may provide a neuroprotective effect against the devastating actions of
      ethanol on hippocampal function.

PMID- 23164618
TI  - Supra-normal stimulation of dopamine D1 receptors in the prelimbic cortex blocks
      behavioral expression of both aversive and rewarding associative memories through
      a cyclic-AMP-dependent signaling pathway.
AB  - Dopamine (DA) receptor transmission through either D(1) or D(2)-like subtypes is
      involved critically in the processing of emotional information within the medial
      prefrontal cortex (mPFC). However the functional role of specific DA D(1)-like
      receptor transmission in the expression of emotionally salient associative
      memories (either aversive or rewarding) is not currently understood. Here we
      demonstrate that specific activation of DA D(1) receptors in the prelimbic (PLC)
      division of the mPFC causes a transient block in the behavioral expression of
      both aversive and rewarding associative memories. We report that intra-PLC
      microinfusions of a selective D(1) receptor agonist block the spontaneous
      expression of an associative olfactory fear memory, without altering the
      stability of the original memory trace. Furthermore, using an unbiased place
      conditioning procedure (CPP), intra-PLC D(1) receptor activation blocks the
      spontaneous expression of an associative morphine (5 mg/kg; i.p.) reward memory,
      while leaving morphine-primed memory expression intact. Interestingly, both intra
      PLC D(1)-receptor mediated block of either fear-related or reward-related
      associative memories were dependent upon downstream cyclic-AMP (cAMP) signaling
      as both effects were rescued by co-administration of a cAMP signaling inhibitor.
      The blockade of both rewarding and aversive associative memories is mediated
      through a D(1)-specific signaling pathway, as neither forms of spontaneous memory
      expression were blocked by intra-PLC microinfusions of a D(2)-like receptor
      agonist. Our results demonstrate that the spontaneous expression of either
      rewarding or aversive emotionally salient memories shares a common, D(1)-receptor
      mediated substrate within the mPFC.

PMID- 23164620
TI  - Induction of Dickkopf-1 contributes to the neurotoxicity of MPP+ in PC12 cells
      via inhibition of the canonical Wnt signaling pathway.
AB  - The secreted glycoprotein Dickkopf-1 (Dkk1), an antagonist of the Wnt/beta
      catenin pathway, has been implicated in many neurodegenerative diseases. However,
      it is unknown whether Dkk1 is involved in the pathogenesis of Parkinson's disease
      (PD). In this study, we discovered that Dkk1 was induced in MPP(+)-treated PC12
      cells and the increase of Dkk1 preceded PC12 cell loss. RhDkk1 aggravated the
      neurotoxicity of MPP(+) in PC12 cells. Furthermore, the level of Dkk1 was
      correlated with the number of apoptotic PC12 cells. The apoptosis could be
      decreased by Dkk1-siRNA in MPP(+)-induced PC12 cells and Dkk1-siRNA regulated the
      expression of beta-catenin and p-Ser9-GSK-3beta in MPP(+)-induced PC12 cells.
      LiCl (an inhibitor of GSK-3beta) also rescued the loss of PC12 cell viability and
      the apoptosis induced by MPP(+). These data suggest that the induction of Dkk1
      contributes to the MPP(+)-induced neurotoxicity in PC12 cells via inhibition of
      the canonical Wnt pathway and Dkk1 antagonists which could rescue the Wnt pathway
      might be neuroprotective in PD.

PMID- 23164619
TI  - Glucose attenuates impairments in memory and CREB activation produced by an
      alpha4beta2 but not an alpha7 nicotinic receptor antagonist.
AB  - Glucose improves memory for a variety of tasks when administered to rats and mice
      near the time of training. Prior work indicates glucose may enhance memory by
      increasing the synthesis and release of the neurotransmitter acetylcholine in the
      brain. To investigate if specific acetylcholine receptor subtypes may mediate
      some of the memory-enhancing actions of glucose, we examined the effects of
      subtype-specific nicotinic acetylcholine receptor antagonists on memory in
      Fischer-344 rats and also examined the ability of glucose to reverse drug-induced
      impairments. Pre-training peripheral injections of methyllycaconitine (MLA) or
      dihydro-beta-erythroidine (DHbetaE), which are specific alpha7 and alpha4beta2
      nicotinic receptor antagonists, respectively, dose-dependently impaired retention
      latencies in an inhibitory avoidance task when tested 7-days but not 1 h after
      training. Immediate post-training glucose injections attenuated the impairments,
      but were more effective in attenuating the DHbetaE-induced impairments. Likewise,
      peripheral or direct intrahippocampal injections of MLA or DHbetaE dose
      dependently impaired spatial working memory scores on a spontaneous alternation
      task. Concurrent administration of glucose reversed DHbetaE- but not MLA-induced
      impairments. CREB phosphorylation downstream of cholinergic signaling was
      assessed 30 min after spontaneous alternation testing and intrahippocampal drug
      infusions. Both MLA and DHbetaE impaired hippocampal CREB phosphorylation;
      glucose reversed DHbetaE- but not MLA-induced deficits. The effectiveness of
      glucose in reversing DHbetaE- but not MLA-induced impairments in behavioral
      performance and CREB phosphorylation suggests that activation of alpha7 receptors
      may play an important role in memory enhancement by glucose.

PMID- 23164621
TI  - Neighborhood effects on heat deaths: social and environmental predictors of
      vulnerability in Maricopa County, Arizona.
AB  - BACKGROUND: Most heat-related deaths occur in cities, and future trends in global
      climate change and urbanization may amplify this trend. Understanding how
      neighborhoods affect heat mortality fills an important gap between studies of
      individual susceptibility to heat and broadly comparative studies of temperature
      mortality relationships in cities. OBJECTIVES: We estimated neighborhood effects
      of population characteristics and built and natural environments on deaths due to
      heat exposure in Maricopa County, Arizona (2000-2008). METHODS: We used 2000 U.S.
      Census data and remotely sensed vegetation and land surface temperature to
      construct indicators of neighborhood vulnerability and a geographic information
      system to map vulnerability and residential addresses of persons who died from
      heat exposure in 2,081 census block groups. Binary logistic regression and
      spatial analysis were used to associate deaths with neighborhoods. RESULTS:
      Neighborhood scores on three factors-socioeconomic vulnerability,
      elderly/isolation, and unvegetated area-varied widely throughout the study area.
      The preferred model (based on fit and parsimony) for predicting the odds of one
      or more deaths from heat exposure within a census block group included the first
      two factors and surface temperature in residential neighborhoods, holding
      population size constant. Spatial analysis identified clusters of neighborhoods
      with the highest heat vulnerability scores. A large proportion of deaths occurred
      among people, including homeless persons, who lived in the inner cores of the
      largest cities and along an industrial corridor. CONCLUSIONS: Place-based
      indicators of vulnerability complement analyses of person-level heat risk
      factors. Surface temperature might be used in Maricopa County to identify the
      most heat-vulnerable neighborhoods, but more attention to the socioecological
      complexities of climate adaptation is needed.

PMID- 23164622
TI  - Prognostic improvement of reexcision for positive resection margins in patients
      with advanced gastric cancer.
AB  - AIM: The aim of this study was to investigate the effect of reexcision for
      advanced gastric cancer (GC) with positive resection margins on prognosis and to
      identify the selection criteria for the reexcision of patients with positive
      margins. PATIENTS AND METHODS: This was a retrospective study of 122 patients
      with positive margins who underwent potentially curative resection for locally
      advanced GC. The clinicopathological factors and survival among 50 patients who
      were reexcised to a negative resection margin (NR group) and 72 patients who were
      left with a positive resection margin (PR group) were compared using univariate
      and multivariate analyses. RESULTS: Median survival in the PR group was 18 months
      compared with 23 months in the NR group (p = 0.019). In the <= pN2-category
      subset, the PR group had a significantly worse prognosis compared with the NR
      group (median survival of 25 months vs. 44 months; p = 0.021). This difference
      was not observed in the pN3-category subset. In the univariate analysis,
      variables including pTNM stage, pN-category, and positive resection margin had
      adverse effects on OS among the entire population of 122 patients. A positive
      margin was confirmed as an independent prognostic factor for OS in the
      multivariate analysis. CONCLUSIONS: The reexcision of a positive margin improves
      the prognosis of patients with advanced GC, especially in those paitents with <=
      pN2-category disease and in patients undergoing D2 lymphadenectomy. Obtaining
      routine frozen sections of samples from the resection margin should be mandatory
      in the treatment of all GC patients undergoing potentially curative surgery.

PMID- 23164623
TI  - Iron telluride nanorods-based system for the detection of total mercury in blood.
AB  - We have developed a simple, colorimetric iron telluride (FeTe) nanorods (NRs)
      based system for the detection of mercury, mainly based on the cation exchange
      reaction between FeTe NRs and Hg(2+). FeTe NRs (length, 105 +/- 21 nm) react with
      Hg(2+) to form HgTe NRs (length, 112 +/- 26 nm) and consequently release Fe(2+)
      ions that catalyzes the oxidation between a peroxidase substrate 2,2'-azino-bis(3
      ethylbenzo-thiazoline-6-sulfonic acid) diammonium salt (ABTS) and H(2)O(2). The
      concentration of Fe(2+) and thereby Hg(2+) can be determined by measuring the
      absorbance of the ABTS oxidized product at 418 nm. This approach allows the
      detection of Hg(2+), with a limit of detection of 1.31 nM at a signal-to-noise
      ratio 3 and a linear range 5-100 nM (R(2)=0.99). The low-cost, simple, sensitive,
      and reproducible assay has been validated for the detection of Hg(2+) in a blood
      sample (SRM 955c), with the result being in good agreement with that provided by
      National Institute of Standards and Technology.

PMID- 23164624
TI  - Molasses enhanced phyto and bioremediation treatability study of explosives
      contaminated Hawaiian soils.
AB  - A 15-week treatability study was conducted in a greenhouse to evaluate the
      potential effects of molasses on the bioremediation and phytoremediation
      potential of Guinea Grass (Panicum maximum) for treating energetic contaminated
      soil from the open burn/open detonation area of the Makua Military Reservation,
      Oahu, HI (USA). The energetics in the soil were royal demolition explosive (RDX)
      and high-melting explosive (HMX). Among the 6 treatments employed in this study,
      enhanced removal of RDX was observed from treatments that received molasses and
      went to completion. The RDX degradation rates in treatments with molasses diluted
      1:20 and 1:40 were comparable suggesting that the lower dose worked as well as
      the higher dose. Treatments without molasses degraded RDX slowly and residuals
      remained after 15 weeks. The bacterial densities in molasses-treated units were
      much greater than those without molasses. Phytoremediation alone seems to have
      little effect on RDX disappearance. For HMX, neither bioremediation nor
      phytoremediation was found to be useful in reducing the concentration within the
      experimental period. The concentrations of nitrogen and phosphorous in the soil
      did not change significantly during the experiment, however, a slight increase in
      soil pH was observed in all treatments. The study showed that irrigating with
      diluted molasses is effective at enhancing RDX degradation mainly in the root
      zone and just below it. The long term sustainability of active training ranges
      can be enhanced by bioremediation using molasses treatments to prevent RDX
      deposited by on-going operations from migrating through the soil to groundwater
      and off-site.

PMID- 23164625
TI  - When allowed, females prefer novel males in the polygynous subterranean rodent
      Ctenomys talarum (tuco-tuco).
AB  - The ability to recognize familiar conspecifics plays an important role at the
      time of choosing a mating partner in rodents. A laboratory study using preference
      test was used in order to test the hypothesis that, in the polygynous
      subterranean rodent Ctenomys talarum, females prefer novel males when offered two
      odors, or individuals (one familiar and one novel) limited in their movements so
      that male aggression is prevented. Our findings show that females prefer novel
      tuco-tucos at three levels of male assessment: odor samples (consisting of
      shavings soiled with urine, feces, and presumably, other body secretions
      collected from the male home cage), confined males behind a wire mesh, and full
      contact with tethered males. Previous studies of this species demonstrated that
      in the wild, male-male competition and male coercion severely limit the
      possibility of females mating non-neighbors, i.e. novel males. Females mating
      neighbors to whom they are familiarized, obtain high quality mating since they
      are territorial, highly competitive males. Nonetheless, when females have the
      opportunity, as shown in the two-choice experiments, they choose novel males,
      probably benefiting their progeny from novel genetic combinations. Hence,
      combining evidence from laboratory and field studies in C. talarum, it is
      possible to better understand female preferences in modeling individual
      reproductive strategies.

PMID- 23164626
TI  - Persistent and anti-persistent pattern in stride-to-stride variability of
      treadmill walking: influence of rhythmic auditory cueing.
AB  - It has been observed that long time series of Stride Time (ST), Stride Length
      (SL) and Stride Speed (SS=SL/ST) exhibited statistical persistence (long-range
      auto-correlation) in overground walking. Rhythmic auditory cueing induced anti
      persistent (or anti-correlated) patterns in ST series, while SL and SS remained
      persistent. On the other hand, it has been shown that SS became anti-persistent
      in treadmill walking, while ST and SL remained persistent. The aim of this study
      was to analyze the effect of the combination of treadmill walking (imposed speed)
      and auditory cueing (imposed cadence) on gait dynamics. Twenty middle-aged
      subjects performed 6*5 min walking trials at various imposed speeds on an
      instrumented treadmill. Freely chosen walking cadences were measured during the
      first three trials, and then imposed accordingly in the last three trials by
      using a metronome. Detrended fluctuation analysis (DFA) was performed on the
      times series of ST, SL, and SS. Treadmill induced anti-persistent dynamics in the
      time series of SS, but preserved the persistence of ST and SL. On the contrary,
      all the three parameters were anti-persistent under dual-constraints condition.
      Anti-persistent dynamics may be related to a tighter control: deviations are
      followed by a rapid over-correction, which produces oscillations around target
      values. Under single constraint condition, while SS is tightly regulated in order
      to follow the treadmill speed, redundancy between ST and SL would likely allow
      persistent pattern to occur. Conversely, under dual constraint conditions, the
      absence of redundancy among SL, ST and SS would explain the generalized anti
      persistent pattern.

PMID- 23164627
TI  - Age-related changes in motor imagery from early childhood to adulthood: probing
      the internal representation of speed-accuracy trade-offs.
AB  - The purpose of this study was to chart the development of motor imagery ability
      between 5 and 29 years of age and its relationship to fine-motor skill. 237
      participants performed a computerized Virtual Radial Fitts Task (VRFT) as a
      measure of Motor Imagery (MI) ability. Participants aimed at five targets,
      positioned along radial axes from a central target circle. The targets differed
      in width over trials (2.5, 5, 10, 20 or 40 mm). Performance was indexed by the
      relationship between the movement time (MT) in executed and imagined movements. A
      subset of participants (11-19 years old, n=22) also performed the task with their
      non-preferred hand. We also examined if manual skill (measured by peg board task
      and posting coins) was related to the executed and imagined MT on the VRFT. Our
      results showed that the accuracy of the imagined movement improved steadily over
      childhood, reaching an asymptote during adolescence and into early adulthood. The
      correlation between the real and virtual MT using the preferred hand did not
      differ appreciably from that using the non-preferred hand. If the children could
      perform the tasks with their non-preferred hand (11 years and older), they also
      scaled performance in relatively precise terms using the less dextrous non
      preferred hand. The correlation between real MT on the VRFT and fine-motor
      performance ranged between .53 and .42, while that for virtual movement was
      between .37 and .34. MI ability predicts manual skill to a moderate degree.

PMID- 23164628
TI  - Self-controlled knowledge of results: age-related differences in motor learning,
      strategies, and error detection.
AB  - Research has demonstrated that a self-controlled KR schedule is advantageous for
      motor learning; however, the usefulness of a self-controlled KR context in older
      adults remains unknown. To address this gap in knowledge, we examined whether (1)
      the learning benefits of a self-controlled KR schedule are modulated by the age
      of the learner; (2) practicing in a self-controlled KR context concurrently
      strengthens the learner's error detection mechanism, and (3) the KR strategy
      during acquisition changes as a function of practice trials completed and age. As
      a function of age, participants were quasirandomly assigned to either the self
      control or yoked group resulting in four experimental groups (Self-Young, Yoked
      Young, Self-Old, and Yoked-Old). The results revealed the Self-Young group: (1)
      demonstrated superior retention performance than all other groups (p<.05); (2)
      was more accurate in estimating motor performance than all other groups during
      retention (p<.05), and (3) self-reported a switch in their strategy for
      requesting KR during acquisition based on the number of practice trials
      completed. Collectively, our findings suggest that older adults do not
      demonstrate the same learning benefits of a self-controlled KR context as younger
      adults which may be attributed to differences in KR strategies.

PMID- 23164629
TI  - Management of neck metastases in T2N0 lip squamous cell carcinoma.
AB  - BACKGROUND: Prophylactic neck dissection (PND) is indicated when the chance of
      occult lymph node metastases from head and neck tumors is significant. There is
      no consensus regarding which tumor size PND would be indicated in cases of lip
      cancer. METHODS: A total of 139 patients with surgically treated lip cancer were
      selected. The size of the lesion (T) and the presence of lymph node metastases
      (N) were assessed by examining the medical records. For analysis purposes, the T2
      group was divided into T2a (2 to 3 cm) and T2b (3 to 4 cm). RESULTS: The
      following distribution of incidence of neck metastases was observed in the study
      groups: 11.7% in T1, 9% in T2a, 43.7% in T2b, and 52.2% in T3+T4. Statistical
      comparison of the groups (p) revealed the following results: T2aXT2b=0.03;
      T2aXT3+T4=0.001. CONCLUSION: PND is indicated for tumors larger than 3 cm.

PMID- 23164630
TI  - The value of resident presentations at scientific meetings.

PMID- 23164631
TI  - Diabetes and cancer: Could vitamin D provide the link?
AB  - Diabetes and cancer are common diseases that may co-exist in the same individual.
      There is significant evidence that patients with diabetes have increased risk of
      developing certain cancers, especially colorectal, pancreatic and primary hepatic
      cancer. There is also good evidence that low levels of vitamin D are associated
      with increased risk of diabetes and increased risk of colorectal, and possibly
      other, cancers. In this article we propose that low levels of vitamin D may
      increase the risk of cancer in people with diabetes and describe potential
      molecular pathways. We suggest that large scale randomised trials of vitamin D
      supplementation in patients at risk of diabetes, and in patients with established
      diabetes to examine the effect on cancer risk, are required.

PMID- 23164632
TI  - Measuring the transition to diabetes.

PMID- 23164633
TI  - A simple greedy algorithm for reconstructing pedigrees.
AB  - This paper introduces a simple greedy algorithm for searching for high likelihood
      pedigrees using micro-satellite (STR) genotype information on a complete sample
      of related individuals. The core idea behind the algorithm is not new, but it is
      believed that putting it into a greedy search setting, and specifically the
      application to pedigree learning, is novel. The algorithm does not require age or
      sex information, but this information can be incorporated if desired. The
      algorithm is applied to human and non-human genetic data and in a simulation
      study.

PMID- 23164634
TI  - Resource transfers and evolution: helpful offspring and sex allocation.
AB  - In some vertebrates, offspring help their parents produce additional offspring.
      Often individuals of one sex are more likely to become "helpers at the nest". We
      analyze how such sex-biased offspring helping can influence sex-ratio evolution.
      It is essential to account for age-structure because the sex ratios of early
      broods influence how much help is available for later broods; previous authors
      have not correctly accounted for this fact. When each female produces the same
      sex ratio in all broods (as assumed in all previous analyses of sex-biased
      helping), the optimal investment strategy is biased towards the more-helpful sex.
      When a female has facultative control over the sex ratio in each brood and each
      helper of a given sex increases the resource available for offspring production
      by a fixed amount, the optimal strategy is to produce only the more-helpful sex
      in early broods and only the less-helpful sex in later broods. When there are
      nonlinear returns from helping, i.e., each helper increases the amount of
      resource available for reproduction by an amount dependent upon the number of
      helpers, the optimal strategy is to maximize resource accrual from helping in
      early broods (which may involve the production of both sexes) and then switch to
      the exclusive production of the less-helpful sex in later broods. The population
      sex ratio is biased towards the more-helpful sex regardless of whether the sex
      ratio is fixed or age-dependent. When fitness returns from helping exhibit
      environmental patchiness, females are selected to produce only males on some
      patches and only females on others, and the population sex ratio may be biased in
      either direction. We discuss our results in light of empirical information on
      offspring helping, and we show via meta-analysis that there is no support for the
      claim of Griffin et al. [Griffin, A.S., Sheldon, B.C., West, S.A., 2005.
      Cooperative breeders adjust offspring sex ratios to produce helpful helpers.
      Amer. Nat. 166, 628-632] that parents produce more of the helpful sex when that
      sex is rare or absent.

PMID- 23164635
TI  - Production of antisera against porcine haptoglobin: potential for distinguishing
      haptoglobin subunits.
AB  - Haptoglobin (Hp) is one of the acute phase proteins (APPs) that help to alleviate
      the immune oxidative damage. The present study expressed a truncated porcine Hp
      in Escherichia coli and produced rabbit and mouse antisera to the recombinant
      protein, in order to investigate Hp levels in sera from piglets infected with
      porcine reproduction and respiratory syndrome virus (PRRSV). Antisera prepared
      revealed both chains of porcine Hp in Western blot, and mouse antisera showed
      stronger binding activities than the rabbit antisera. With the combination of Hp
      monoclonal antibodies, this study confirmed that serum Hp was increased in
      piglets infected with PRRSV and offered a tool to know about subunit levels of Hp
      in porcine serum. But Hp itself could not be used as a specific biomarker for
      PRRSV infection, for elevated Hp levels were also obtained from pigs infected
      with other pathogens.

PMID- 23164636
TI  - Characterization of cytotoxicity-related gene expression in response to virulent
      Marek's disease virus infection in the bursa of Fabricius.
AB  - Cell-mediated cytotoxic responses are critical for control of Marek's disease
      virus (MDV) infection and tumour development. However, the mechanisms of virus
      clearance mediated by cytotoxic responses in the bursa of Fabricius of chickens
      during MDV infection are not fully understood. In this study, the host cytotoxic
      responses during MDV infection in the bursa were investigated by examining the
      expression of genes in the cell lysis pathways. Partial up-regulation existed in
      the expression of the important cytolytic molecule granzyme A (GzmA), Fas, NK
      lysin and DNA repair enzyme Ape1, whereas little or no expression appeared in
      other cytolytic molecules, including perforin (PFN) and Fas ligand (FasL), and
      molecules involved in DNA repair and apoptosis in the bursa during MDV infection.
      These results suggest that less sustained cytotoxic activities are generated in
      the bursa of MDV-infected chickens. The findings of this study provide a more
      detailed insight into the host cytotoxic responses to MDV infection.

PMID- 23164637
TI  - Diabetes mellitus remission after resolution of inflammatory and progesterone
      related conditions in bitches.
AB  - Canine diabetes mellitus (CDM) remission is a rare event that is possible after
      the resolution of insulin resistance conditions, especially those related to the
      estrus cycle. A retrospective study was carried out at the Division of Veterinary
      Endocrinology from 2006 to 2011 to assess CDM remission rates after the
      resolution of problems associated with ovarian activity. Out of 117 female dogs
      diagnosed with CDM, six diabetes remission cases were identified and described
      after resolution of diestrus (1), or after ovariohysterectomy for pregnancy (1),
      ovarian remnant syndrome (1), and pyometra (3), even after initial presentation
      in severe diabetic ketosis or long after diagnosis (ovariohysterectomy was
      performed from 3 to 81 days after diagnosis, and diabetes resolution was achieved
      within 4-39 days after gonadectomy). Several factors may lead to diabetes
      remission. However, in these cases, ovariohysterectomy was crucial for the
      restoration of normal blood glucose levels, suggesting that diabetic bitches be
      spayed independently of the length of time after diagnosis.

PMID- 23164638
TI  - Tips and traps in neurological imaging: imaging the perimedullary spaces.
AB  - The spinal canal is frequently a source of difficulties, traps and diagnostic
      errors. Pitfalls related to artifacts are resolved by using appropriate
      sequences. Good knowledge of the appearance of certain particular anatomical
      structures (the cauda equina roots, the radicular veins of the lumbar spine and
      conus medullaris, the dorsal root ganglion) and of frequent variants (fibrolipoma
      of the filum terminale, common root sheaths, root cysts) will avoid a good many
      errors. Dilatation of epidural veins in intracranial hypotension can simulate the
      contrast enhancement of a tumour. An increase in epidural fat can induce
      pathogenic stenosis of the dural sheath.

PMID- 23164639
TI  - Functional interaction of glutathione S-transferase pi and peroxiredoxin 6 in
      intact cells.
AB  - Peroxiredoxin 6 (Prdx6) is a 1-Cys member of the peroxiredoxin superfamily that
      plays an important role in antioxidant defense. Glutathionylation of recombinant
      Prdx6 mediated by pi glutathione S-transferase (GST) is required for reduction of
      the oxidized Cys and completion of the peroxidatic catalytic cycle in vitro. This
      study investigated the requirement for piGST in intact cells. Transfection with a
      plasmid construct expressing piGST into MCF7, a cell line that lacks endogenous
      piGST, significantly increased phospholipid peroxidase activity as measured in
      cell lysates and protected intact cells against a peroxidative stress. siRNA
      knockdown indicated that this increased peroxidase activity was Prdx6 dependent.
      Interaction between piGST and Prdx6, evaluated by the Duolink Proximity Ligation
      Assay, was minimal under basal conditions but increased dramatically following
      treatment of cells with the oxidant, tert-butyl hydroperoxide. Interaction was
      abolished by mutation of C47, the active site for Prdx6 peroxidase activity.
      Depletion of cellular GSH by treatment of cells with buthionine sulfoximine had
      no effect on the interaction of Prdx6 and piGST. These data are consistent with
      the hypothesis that oxidation of the catalytic cysteine in Prdx6 is required for
      its interaction with piGST and that the interaction plays an important role in
      regenerating the peroxidase activity of Prdx6.

PMID- 23164640
TI  - Answer to the letter to the editor "Quantitative bone ultrasound in pediatric
      patients with cystic fibrosis".

PMID- 23164641
TI  - Expression of the inflammatory regulator A20 correlates with lung function in
      patients with cystic fibrosis.
AB  - BACKGROUND: A20 and TAX1BP1 interact to negatively regulate NF-kappaB-driven
      inflammation. A20 expression is altered in F508del/F508del patients. Here we
      explore the effect of CFTR and CFTR genotype on A20 and TAX1BP1 expression. The
      relationship with lung function is also assessed. METHODS: Primary nasal
      epithelial cells (NECs) from CF patients (F508del/F508del, n=7, R117H/F508del,
      n=6) and controls (age-matched, n=8), and 16HBE14o- cells were investigated. A20
      and TAX1BP1 gene expression was determined by qPCR. RESULTS: Silencing of CFTR
      reduced basal A20 expression. Following LPS stimulation A20 and TAX1BP1
      expression was induced in control NECs and reduced in CF NECs, broadly reflecting
      the CF genotype: F508del/F508del had lower expression than R117H/F508del. A20,
      but not TAX1BP1 expression, was proportional to FEV(1) in all CF patients
      (r=0.968, p<0.001). CONCLUSIONS: A20 expression is reduced in CF and is
      proportional to FEV1. Pending confirmation in a larger study, A20 may prove a
      novel predictor of CF inflammation/disease severity.

PMID- 23164642
TI  - Intraoperative hypercyanosis in a patient with pulmonary artery band: case report
      and review of the literature.
AB  - A case of intraoperative cyanosis in a patient with a common atrioventricular
      canal palliated with a pulmonary artery (PA) band is presented. The patient's
      physiology was consistent with cyanosis due to inadequate pulmonary blood flow,
      and responded quickly to typical interventions used for a hypercyanotic episode
      in a patient with unrepaired Tetralogy of Fallot. Differences and similarities in
      the physiology of PA banding compared with Tetralogy of Fallot are presented,
      including a rationale for treatment options for hemodynamic decompensation
      occurring in the setting of anesthesia and surgery.

PMID- 23164643
TI  - A novel way to repurpose waste to improve operating room hygiene.

PMID- 23164644
TI  - Severe anaphylactoid reaction to thymoglobulin in a pediatric renal transplant
      recipient.
AB  - Intraoperative administration of thymoglobulin is an integral part of the anti
      rejection regimen during organ transplantation. However, its administration may
      be associated with complications. An anaphylactoid reaction that occurred in a
      pediatric recipient of a living-related renal transplant, on initiating an
      intravenous infusion of thymoglobulin, is presented.

PMID- 23164645
TI  - BrainLAB interference with pulse oximetry during stereotactic brain biopsy.

PMID- 23164646
TI  - Analysing the development of road safety using demographic data.
AB  - The purpose of this paper is to show that time series analyses of road safety and
      risk can be improved by using demographic data. We demonstrate that the distance
      travelled by drivers or riders of a certain age reflects the fluctuations over
      the years of the number of people of that age within the population. We further
      demonstrate that the change over time of per capita distance travelled, i.e.
      distance travelled per person, is often less subject to stochastic fluctuations,
      and therefore more smooth than the total distance travelled for drivers of that
      age. This smoothness is used to obtain forecasts of distance travelled, or to
      average out year-to-year fluctuations of data of distance travelled. Analysis of
      such data stratified by age group, gender or both reveals that, for most travel
      modes, per capita distance travelled is to a large extent constant or slowly
      changing over time. The consequences for the evaluation of risk, i.e. casualties
      per distance travelled, with and without the use of population data, are
      explored. Dutch data are used to illustrate the model concept. It is shown that
      the analyses and forecasts of distance travelled could gain substantially by
      incorporating demographic data, as compared to an analysis with data of distance
      travelled alone. The paper further shows that, for an analysis of risk and
      therefore for traffic safety forecasts in the absence of any data of distance
      travelled, stratified analysis of mortality, i.e. casualties per inhabitant, may
      be a reasonable alternative. 

PMID- 23164647
TI  - Oral creatine supplementation's decrease of blood lactate during exhaustive,
      incremental cycling.
AB  - PURPOSE: To determine the effects of creatine supplementation on blood lactate
      during incremental cycling exercise. METHODS: Thirteen male subjects (M +/- SD 23
      +/- 2 yr, 178.0 +/- 8.1 cm, 86.3 +/- 16.0 kg, 24% +/- 9% body fat) performed a
      maximal, incremental cycling test to exhaustion before (Pre) and after (Post) 6 d
      of creatine supplementation (4 doses/d of 5 g creatine + 15 g glucose). Blood
      lactate was measured at the end of each exercise stage during the protocol, and
      the lactate threshold was determined as the stage before achieving 4 mmol/L.
      Lactate concentrations during the incremental test were analyzed using a 2
      (condition) * 6 (exercise stage) repeated-measures ANOVA. Differences in power at
      lactate threshold, power at exhaustion, and total exercise time were determined
      by paired t tests and are presented as M +/- SD. RESULTS: Lactate concentrations
      were reduced during exercise after supplementation, demonstrating a significant
      condition effect (p = .041). There was a tendency for increased power at the
      lactate threshold (Pre 128 +/- 45 W, Post 143 +/- 26 W; p = .11). Total time to
      fatigue approached significant increases (Pre 22.6 +/- 3.2 min, Post 23.3 +/- 3.3
      min; p = .056), as did maximal power output (Pre 212.5 +/- 32.5 W, Post 220 +/-
      34.6 W; p = .082). CONCLUSIONS: Our findings demonstrate that creatine
      supplementation decreases lactate during incremental cycling exercise and tends
      to raise lactate threshold. Therefore, creatine supplementation could potentially
      benefit endurance athletes.

PMID- 23164648
TI  - Measuring surface temperature and grading pathological changes of airway tissue
      in a canine model of inhalational thermal injury.
AB  - BACKGROUND: Airway tissue shows unexpected invulnerability to heated air. The
      mechanisms of this phenomenon are open to debate. OBJECTIVE: This study was
      designed to measure the surface temperatures at different locations of the
      airway, and to explore the relationship between the tissue's surface temperature
      and injury severity. METHOD: Twenty dogs were randomly divided into four groups,
      including three experimental groups (six dogs in each) to inhale heated air at 70
      80  degrees C (group I), 150-160  degrees C (group II) and 310-320  degrees C
      (group III) and a control group (two dogs, only for histological observation).
      Injury time was 20 min. Mucosal surface temperatures of the epiglottis (point A),
      cricoid cartilage (point B) and lower trachea (point C) were measured. Dogs in
      group I-III were divided into three subgroups (two in each), to be assayed at 12,
      24 and 36 h after injury, respectively. For each dog, four tissue parts
      (epiglottis, larynx, lower trachea and terminal bronchiole) were microscopically
      observed and graded according to an original pathological scoring system (score
      range: 0-27). RESULT: Surface temperatures of the airway mucosa increased slowly
      to 40.60+/-3.29  degrees C, and the highest peak temperature was 48.3  degrees C
      (group III, point A). The pathological score of burned tissues was 4.12+/-4.94
      (0.0-18.0), suggesting slight to moderate injuries. Air temperature and airway
      location both influenced mucosal temperature and pathological scores very
      significantly, and there was a very significant positive correlation between
      tissue temperature and injury severity. CONCLUSION: Compared to the inhalational
      air hyperthermia, airway surface temperature was much lower, but was still
      positively correlated with thermal injury severity.

PMID- 23164650
TI  - [Gestational recurrent of ischemic stroke event].

PMID- 23164649
TI  - Thyroid hormones in relation to lead, mercury, and cadmium exposure in the
      National Health and Nutrition Examination Survey, 2007-2008.
AB  - BACKGROUND: Heavy metals, such as lead (Pb), mercury (Hg), and cadmium (Cd), are
      known toxicants, but their associations with the thyroid axis have not been well
      quantified at U.S. background levels. OBJECTIVES: We investigated the
      relationships between thyroid hormones (total and free thyroxine [TT4 and FT4],
      total and free triiodothyronine [TT3 and FT3], thyroid-stimulating hormone [TSH],
      and thyroglobulin [Tg]) and levels of Pb, Hg, and Cd in blood and Cd in urine.
      METHODS: We separately analyzed a sample of 1,109 adolescents (12-19 years of
      age) and a sample of 4,409 adults from the U.S. National Health and Nutrition
      Examination Survey (NHANES) 2007-2008. We estimated associations after adjusting
      for age, sex, race, urinary iodine, body mass index, and serum cotinine. RESULTS:
      The geometric mean (GM) levels of blood Pb (BPb), total Hg, and Cd were 0.81
      ug/dL, 0.47 ug/L, and 0.21 ug/L in adolescents and 1.43 ug/dL, 0.96 ug/L, and
      0.38 ug/L in adults, respectively. The GMs of urinary Cd were 0.07 and 0.25 ug/g
      creatinine in adolescents and adults, respectively. No consistent pattern of
      metal and thyroid hormone associations was observed in adolescents. In adults,
      blood Hg was inversely related to TT4, TT3, and FT3 and urinary Cd was positively
      associated with TT4, TT3, FT3, and Tg, but there were no associations with Pb.
      Associations were relatively weak at an individual level, with about 1-4% change
      in thyroid hormones per interquartile range increase in Hg or Cd. CONCLUSIONS:
      Our analysis suggests an inverse association between Hg exposure and thyroid
      hormones, and a positive association between Cd exposure and thyroid hormones in
      adults.

PMID- 23164651
TI  - [Prehospital use of haemostatic dressing QuikClot ACS+TM for hemorrhage control
      of a perineal trauma].
AB  - First responders are sometimes confronted with external uncontrolled haemorrhage
      despite compression, bandages, and tourniquets. Several topical haemostatic
      agents were developed to try to face these situations. Their application was
      mainly described and studied in military environment. We report the case of a
      worker victim of an accident of construction site with hemorrhagic perineal
      trauma for whom the use of a haemostatic bandage QuikClot ACS+TM (Z-Medica)
      seemed to us particularly useful in prehospital setting.

PMID- 23164652
TI  - [Breakage of the interface blade-laryngoscope handle during a laryngoscopy
      (context of surgical recovery and potentially difficult tracheal intubation)].

PMID- 23164653
TI  - [Phaeochromocytoma revealed by a cardiogenic shock treated by extracorporeal life
      support].
AB  - Phaeochromocytoma is a catecholamine-secreting tumour that originates from the
      chromaffin cells in the adrenal medulla in 85% of the cases. Phaeochromocytoma
      typically presents with the classic signs and symptoms of paroxysmal
      hypertension, tachycardia, and episodic headache in young adults. However, it
      rarely may manifest as cardiogenic shock due to a catecholamine induced
      cardiomyopathy. We report the use of central extracorporeal life support (ECLS)
      in a young man admitted to our department because of cardiogenic shock caused by
      phaeochromocytoma.

PMID- 23164654
TI  - [Videolaryngoscopy: benefits for double-lumen tube insertion].

PMID- 23164655
TI  - Bilateral recurrent motor branch of median nerve neuropathy following long
      distance cycling.

PMID- 23164656
TI  - Synthesis, structure-activity relationships, and docking studies of N
      phenylarylformamide derivatives (PAFAs) as non-nucleoside HIV reverse
      transcriptase inhibitors.
AB  - A series of N-phenylarylformamide derivatives (PAFAs) with anti-wild-type HIV-1
      activity (EC(50) values) ranging from 0.3 nM to 5.1 nM and therapeutic index (TI)
      ranging from 10 616 to 271 000 were identified as novel non-nucleoside reverse
      transcriptase inhibitors. Among them, compound 13g (EC(50) = 0.30 nM, TI = 184
      578), 13l (EC(50) = 0.37 nM, TI = 212 819), 13m (EC(50) = 0.32 nM, TI = 260 617)
      and 13r (EC(50) = 0.27 nM, TI = 271 000) displayed the highest activity against
      this type virus nearly as potent as lead compound GW678248. Moreover, all of them
      were also active to inhibit the double mutant strain A(17) (K103N + Y181C) with
      EC(50) values of 0.29 MUM, 0.14 MUM, 0.10 MUM and 0.27 MUM, respectively. In
      particular, compound 13m, which showed broad-spectrum anti-HIV activity, was also
      effective to inhibit the HIV-2 ROD replication within 4.37 MUM concentration.

PMID- 23164657
TI  - beta-Lactam synthon-interceded diastereoselective synthesis of functionalized
      octahydroindole-based molecular scaffolds and their in vitro cytotoxic
      evaluation.
AB  - A convenient and unprecedented synthesis of functionally enriched octahydroindole
      based scaffolds has been developed via inter- and intra-molecular amidolysis of C
      3 functionalized beta-lactams. The cytotoxic evaluation on oesophageal cancer
      cell line WHCO1 has revealed 7d as the most potent of the test compounds
      exhibiting an IC(50) value of 12.97 MUM. The developed strategy further assumes
      significance as it entails the preparation of highly functionalized indoles
      without the aid of transition metal catalysis or pre-functionalization of
      substrates.

PMID- 23164658
TI  - 2-Arylbenzofuran-based molecules as multipotent Alzheimer's disease modifying
      agents.
AB  - The complex etiology of Alzheimer's disease prompts scientists to develop multi
      target strategies to combat causes and symptoms. In line with this modern
      paradigm and as a follow-up to our previous studies, we designed and synthesized
      a focused collection of new 2-arylbenzofurans and evaluated their biological
      properties towards specific targets involved in AD, namely human AChE and human
      BuChE, and Abeta fibril formation. Selected compounds were also tested for their
      ability to inhibit Abeta neurotoxicity in terms of neuronal viability loss, and
      to prevent Abeta peptide-binding to cell membrane and intracellular reactive
      oxygen species (ROS) formation. The different modifications introduced in the
      structure of our lead compound led to an increase in activity towards one or more
      of the selected targets: the anticholinesterase activity of some compounds was
      found to be significantly higher than previously obtained related molecules, and
      the compounds also proved to possess Abeta anti-aggregating properties and
      neuroprotective effects. The most interesting multi-target compounds were 18, and
      1. Interestingly, 1 also showed good selectivity and moderate affinity for CB1
      receptor, opening new perspectives in the field of research on AD, since
      cannabinoid ligands have been widely reported to have neuroprotective properties.

PMID- 23164659
TI  - Synthesis, structural characterization and in vitro cytotoxicity of diorganotin
      (IV) diimido complexes.
AB  - Reactions of the diorganotin with two N-OH diimide ligands (N-hydroxyphthalimide
      and N-hydroxysuccinimide) yielded five new dimeric tetraorganostannoxanes
      formulated as R(8)Sn(4)O(2)L(2)X(2). The crystal structures of the complexes
      reveal the formation of the tetranuclear species contains a planar Sn(4)O(4)
      core, consisting of three adjacent rhombs with bridging oxo and N-OH diimide
      ligands. The central tin atoms are five-coordinated to assume a distorted
      trigonal bipyramidal configuration and the N-OH diimide ligands act as
      monodentate O-bound planar. In vitro cytotoxic activities of the title compounds
      have been determined against three cell lines (A549, HCT-8 and HL-60). Studies
      reveal that three di-n-butyltin(IV) diimido complexes show higher cytotoxic
      activities than cisplatin. The structure-activity relationship of the
      cytotoxicity of the title complexes has also been discussed.

PMID- 23164660
TI  - Synthesis and biological evaluation of 2,3-diarylimidazo[1,2-a]pyridines as
      antileishmanial agents.
AB  - A novel series of 2,3-diarylimidazo[1,2-a]pyridines was synthesized and evaluated
      for their antileishmanial activities. Four derivatives exhibited good activity
      against the promastigote and intracellular amastigote stages of Leishmania major,
      coupled with a low cytotoxicity against the HeLa human cell line. The impact of
      compound lipophilicity on antiparasitic activities was investigated by Log D
      comparison. Although LmCK1 could be the parasitic target for three compounds (13,
      18, 21), the inhibition of another target is under study to explain the
      antileishmanial effect of the most promising compounds.

PMID- 23164662
TI  - Burkitt lymphomagenesis linked to MYC plus PI3K in germinal center B cells.

PMID- 23164663
TI  - DNA photolyases and SP lyase: structure and mechanism of light-dependent and
      independent DNA lyases.
AB  - Light is essential for many critical biological processes including vision,
      circadian rhythms, photosynthesis and DNA repair. DNA photolyases use light
      energy and a fully reduced flavin cofactor to repair the major UV-induced DNA
      damages, the cis-syn cyclobutane pyrimidine dimers (CPDs) and the pyrimidine
      pyrimidone (6-4) photoproducts. Catalysis involves two photoreactions, the
      photoactivation which leads to the conversion of the flavin cofactor to its
      catalytic active form and the photorepair whose efficiency depends on a light
      harvesting antenna chromophore. Very interestingly, an alternative and light
      independent direct reversal mechanism to repair a distinct photolesion is found
      in bacterial spores, catalyzed by spore photoproduct lyase. This radical SAM
      enzyme uses an iron-sulfur cluster and S-adenosyl-l-methionine (SAM) to split a
      specific photoproduct, the so-called spore photoproduct (SP), back to two
      thymidine residues. The recently solved crystal structure of SP lyase provides
      new insights into this unique DNA repair mechanism and allows a detailed
      comparison with DNA photolyases. Similarities as well as divergences between DNA
      photolyases and SP lyase are highlighted in this review.

PMID- 23164661
TI  - Differential gene expression profile of the calanoid copepod, Pseudodiaptomus
      annandalei, in response to nickel exposure.
AB  - To better understand the underlying mechanisms of reactions of copepods exposed
      to elevated level of nickel, the suppression subtractive hybridization (SSH) was
      used to elucidate the response of the copepod Pseudodiaptomus annandalei to
      nickel exposure at the gene level. P. annandale is one of a few copepod species
      that can be cultured relatively easy under laboratory condition, and it is
      considered to be a potential model species for toxicity study. In the present
      study, P. annandalei were exposed to nickel at a concentration of 8.86 mgL(-1)
      for 24h, after which the RNA was prepared for SSH using unexposed P. annandalei
      as drivers. A total of 474 clones on the middle scale in the SSH library were
      sequenced. Among these genes, 129 potential functional genes were recognized
      based on the BLAST searches in NCBI and Uniprot databases. These genes were then
      categorized into nine groups in association with different biological processes
      using AmiGO against the Gene Ontology database. Of the 129 genes, 127
      translatable DNA sequences were predicted to be proteins, and the putative amino
      acid sequences were searched for conserved domains (CD) and proteins using the CD
      Search service and BLASTp. Among 129 genes, 119 (92.2%) were annotated to be
      involved in different biological processes, while 10 genes (7.8%) were classified
      as an unknown-function gene group. To further confirm the up-regulation of
      differentially expressed genes, the quantitative real time PCR were performed to
      test eight randomly selected genes, in which five of them, i.e. alpha-tubulin,
      ribosomal protein L13, ferritin, separase and Myohemerythrin-1, exhibited clear
      up-regulation after nickel exposure. In addition, MnSOD was further studied for
      the differential expression pattern after nickel exposure and the results showed
      that MnSOD had a time- and dose-dependent expression pattern in the copepod after
      nickel exposure. To the best of our knowledge, this is the first attempt to
      investigate the toxicity effects of nickel on a copepod at molecular level.

PMID- 23164665
TI  - Nickel-regulated heart rate variability: the roles of oxidative stress and
      inflammation.
AB  - Heart rate variability (HRV) has been reported to be a putative marker of cardiac
      autonomic imbalance caused by exposure to ambient particulate matter (PM). Our
      objective in this study was to determine the effects on HRV from exposure to
      nickel, an important chemical component of ambient PM that results in oxidative
      stress and inflammation. HRV data were collected for 72 h before lung exposure
      (baseline) and 72 h after intratracheal exposure (response) to nickel sulphate
      (NiSO(4); 526 MUg) in Wistar Kyoto (WKY) and spontaneously hypertensive (SH)
      rats. The antioxidant N-acetyl-L-cysteine (NAC) and the anti-inflammatory
      celecoxib were intraperitoneally injected to examine post-exposure oxidative and
      inflammatory responses. Self-controlled experiments examined the effects of
      NiSO(4) exposure on average normal-to-normal intervals (ANN), natural logarithm
      transformed standard deviation of the normal-to-normal intervals (LnSDNN) and
      root mean square of successive differences of adjacent normal-to-normal intervals
      (LnRMSSD); the resulting data were sequentially analysed using the generalised
      estimating equation model. HRV effects on NiSO(4)-exposed SH rats were greater
      than those on NiSO(4)-exposed WKY rats. After adjusted the HRV responses in the
      WKY rats as control, ANN and LnRMSSD were found to be quadratically increased
      over 72 h after exposure to NiSO(4). Both NAC and celecoxib mitigated the NiSO(4)
      induced alterations in HRV during the exposure period. The results suggest that
      concurrent Ni-induced oxidative stress and inflammatory responses play important
      roles in regulating HRV. These findings help bridge the gap between
      epidemiological and clinical studies on the plausible mechanisms of the
      cardiovascular consequences induced by chemical components in ambient PM.

PMID- 23164664
TI  - 2,3,7,8-TCDD enhances the sensitivity of mice to concanavalin A immune-mediated
      liver injury.
AB  - Inflammation plays a major role in immune-mediated liver injury, and exposure to
      environmental pollutants such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) has
      been reported to alter the inflammatory response as well as affect immune cell
      activity. In this study, we tested the hypothesis that TCDD pretreatment
      exacerbates hepatotoxicity in a murine model of immune-mediated liver injury
      induced by concanavalin A (Con A) administration. Mice were pretreated with 30
      MUg/kg TCDD or vehicle control on day zero and then given either Con A or saline
      intravenously on day four. Mice treated with TCDD did not develop liver injury;
      however, TCDD pretreatment increased liver injury resulting from moderate doses
      of Con A (4-10 mg/kg). TCDD-pretreated mice had altered plasma concentrations of
      inflammatory cytokines, including interferon gamma (IFNgamma), and TCDD/Con A
      induced hepatotoxicity was attenuated in IFNgamma knockout mice. At various times
      after treatment, intrahepatic immune cells were isolated, and expression of cell
      activation markers as well as cytolytic proteins was determined. TCDD
      pretreatment increased the proportion of activated natural killer T (NKT) cells
      and the percent of cells expressing Fas ligand (FasL) after Con A administration.
      In addition FasL knockout mice and mice treated with CD18 antiserum were both
      protected from TCDD/Con A-induced hepatotoxicity, suggesting a requirement for
      direct cell-cell interaction between effector immune cells and parenchymal cell
      targets in the development of liver injury from TCDD/Con A treatment. In summary,
      exposure to TCDD increased NKT cell activation and exacerbated immune-mediated
      liver injury induced by Con A through a mechanism involving IFNgamma and FasL
      expression.

PMID- 23164666
TI  - Inorganic arsenic impairs differentiation and functions of human dendritic cells.
AB  - Experimental studies have demonstrated that the antileukemic trivalent inorganic
      arsenic prevents the development of severe pro-inflammatory diseases mediated by
      excessive Th1 and Th17 cell responses. Differentiation of Th1 and Th17 subsets is
      mainly regulated by interleukins (ILs) secreted from dendritic cells (DCs) and
      the ability of inorganic arsenic to impair interferon-gamma and IL-17 secretion
      by interfering with the physiology of DCs is unknown. In the present study, we
      demonstrate that high concentrations of sodium arsenite (As(III), 1-2 MUM)
      clinically achievable in plasma of arsenic-treated patients, block
      differentiation of human peripheral blood monocytes into immature DCs (iDCs) by
      inducing their necrosis. Differentiation of monocytes in the presence of non
      cytotoxic concentrations of As(III) (0.1 to 0.5 MUM) only slightly impacts
      endocytotic activity of iDCs or expression of co-stimulatory molecules in cells
      activated with lipopolysaccharide. However, this differentiation in the presence
      of As(III) strongly represses secretion of IL-12p70 and IL-23, two major
      regulators of Th1 and Th17 activities, from iDCs stimulated with different toll
      like receptor (TLR) agonists in metalloid-free medium. Such As(III)-exposed DCs
      also exhibit reduced mRNA levels of IL12A and/or IL12B genes when activated with
      TLR agonists. Finally, differentiation of monocytes with non-cytotoxic
      concentrations of As(III) subsequently reduces the ability of activated DCs to
      stimulate the release of interferon-gamma and IL-17 from Th cells. In conclusion,
      our results demonstrate that clinically relevant concentrations of inorganic
      arsenic markedly impair in vitro differentiation and functions of DCs, which may
      contribute to the putative beneficial effects of the metalloid towards
      inflammatory autoimmune diseases.

PMID- 23164667
TI  - [Inferior alveolar nerve block with ropivacaine: effect on nausea and vomiting
      after mandibular osteotomy].
AB  - INTRODUCTION: Our objective was to evaluate the contribution of bilateral
      inferior alveolar nerve block (BIANB) in patients before mandibular sagittal
      osteotomy for postoperative pain management, consumption of opioids, treatment of
      nausea and vomiting. MATERIALS AND METHODS: We included 30 patients undergoing
      mandibular sagittal osteotomy in a prospective, randomized, double blind study.
      The first group of patients (n=14) underwent a standard procedure (general
      anesthesia with postoperative morphine treatment). The second group of patients
      (n=16) underwent BIANB before surgery, in addition to the standard procedure. The
      postsurgical management was evaluated every four hours for the first 24hours,
      according to the following criteria: postoperative nausea and vomiting (PONV),
      visual analogue scale (VAS) assessment of pain, consumption of morphine
      (cumulative dose) and antiemetic drugs, and need for releasing inter-maxillary
      blockage. RESULTS: PONV was significantly less frequent in the second group (6.3
      % versus 42.9 %, P=0.031). The frequency of releasing inter-maxillary blockage
      and the consumption of antiemetic drugs were not significantly different in the
      two groups. The mean VAS pain score was significantly lower in the second group
      (1.6 versus 0.9 avec P=0.045). There was no significant difference in cumulative
      morphine requirements between the two groups at 24hours. DISCUSSION: BIANB during
      mandibular osteotomy increases the patient comfort by decreasing PONV and
      improving postsurgical analgesia.

PMID- 23164669
TI  - Drug-induced lupus erythematosus.
AB  - Drug-induced lupus erythematosus (DILE) refers to a condition whose clinical,
      histological, and immunological features are similar to those seen in idiopathic
      lupus erythematosus but that occurs when certain drugs are taken and resolves
      after their withdrawal. Over 90 drugs have been linked to DILE to date and the
      list is growing. Like idiopathic lupus erythematosus, DILE has systemic, subacute
      cutaneous, and chronic cutaneous forms. A correct diagnosis is very important, as
      this condition usually resolves after withdrawal of the offending drug. 

PMID- 23164670
TI  - The 12th International Congress of Shoulder and Elbow Surgery.

PMID- 23164671
TI  - The usefulness of densitometry as a method of assessing the nutritional status of
      athletes. Comparison with body mass index.
AB  - The body mass index (BMI) is used to assess nutritional status. The result in
      athletes may be overestimated due to increase in muscle mass. OBJECTIVE: To
      assess the usefulness of fat mass index (FMI) and lean mass index (LMI)
      determination as indicators of nutritional status and to compare the results with
      BMI. MATERIAL AND METHODS: We studied 28 amateur rugby players, male. After being
      subjected to whole body densitometry by dual X-ray absorptiometry, we determined
      fat and lean body mass together with other parameters. FMI (fat in kg/height in
      meters(2)), LMI (lean in kg/height in meters(2)) and appendicular muscle mass
      index (AMMI, arms and legs musculature in kg/height in meters(2)) were
      calculated. RESULTS: Using BMI, 18 players were overweight and 4 obese type I.
      Considering FMI, 7 of them had normal values and high LMI and AMMI, one of them
      changed from overweight to obese and another one from obese to overweight. Of the
      6 players with normal BMI, one of them showed fat excess and another one fat
      defect. The results changed the assessment of nutritional status in 39% of
      players. CONCLUSIONS: Although BMI is an appropriate parameter in general
      population for the assessment of nutritional status, in athletes should be taken
      into account fat and muscle body percentage and their corresponding indexes. The
      whole body densitometry appears to be a simple and reliable technique for this
      purpose.

PMID- 23164672
TI  - The dynamics of accumulation of PCBs in cultured adipocytes vary with the cell
      lipid content and the lipophilicity of the congener.
AB  - Lipophilic pollutants such as polychlorinated biphenyls (PCBs) accumulate in high
      amounts in the adipose tissue. Recent epidemiological studies correlate their
      presence in fat cells to possible alterations in the regulation of lipid
      metabolism. The factors governing their accumulation dynamics, storage and
      release in/from fat cells remain however unclear. Several in vitro models of
      cultured adipocytes can be used to address these questions. Nevertheless, the
      cell culture system as well as the PCB congener may influence the behavior of
      such pollutants toward adipocytes and thus the results obtained. In the present
      study, we compared the accumulation of 3 PCB congeners (PCB-28, -118 and -153)
      during a 4-h period in two common models of cultured adipocytes (mouse embryonic
      fibroblasts (MEFs) differentiated into adipocytes and differentiated 3T3-L1
      cells). The results show that adipocytes from different models accumulate
      significantly different amounts of a same pollutant added at the same initial
      concentration in the culture medium. These amounts were strongly correlated to
      the amounts of triglycerides stored in cells. Moreover, the dynamics of
      accumulation varied between the three congeners, PCB-28 entering the cells more
      rapidly than the two other congeners. The lipophilicity of these molecules, shown
      by the partition coefficient (logP) appears to be a major parameter governing
      their uptake dynamics in fat cells.

PMID- 23164673
TI  - The glycogen synthase kinase-3beta/nuclear factor-kappa B pathway is involved in
      cinobufagin-induced apoptosis in cultured osteosarcoma cells.
AB  - Cinobufagin, a major component of cinobufacini (huachansu), is an important
      cardenolidal steroid. Several studies have suggested that cinobufagin has potent
      anti-cancer effects. The present study examines the apoptosis-inducing activity
      and the underlying mechanism of action of cinobufagin in osteosarcoma (OS) cells.
      Our results showed that cinobufagin potently inhibited the proliferation of U2OS,
      MG63 and SaOS-2 cells. Significant increases in G2/M cell-cycle arrest and
      apoptosis in OS cells were also observed. The expression levels of several
      apoptotic proteins were assessed after cinobufagin treatment in U2OS cells. Among
      them, xIAP, cIAP-1, survivin and Bcl-2 levels decreased remarkably, while the
      levels of Bax and cleaved-PARP increased. Furthermore, we validated the
      inhibition of GSK-3beta/NF-kappaB signaling following cinobufagin treatment.
      Western blots showed a decrease in nuclear p65 protein expression after exposure
      to different concentrations of cinobufagin, while the phosphorylation of GSK
      3beta was simultaneously increased. Transduction with constitutively active forms
      of GSK-3beta could protect against the downregulation of p65 and upregulation of
      cleaved-PARP that are induced by cinobufagin treatment. However, combined
      treatment with cinobufagin and SB216367 resulted in a significant reduction in
      p65 and an increase in cleaved-PARP in U2OS cells. Altogether, these results show
      that cinobufagin is a promising agent for the treatment of OS. These studies are
      the first to reveal the involvement of the GSK-3beta/NF-kappaB pathway in
      cinobufagin-induced apoptosis.

PMID- 23164675
TI  - Human reference values for acute airway effects of five common ozone-initiated
      terpene reaction products in indoor air.
AB  - Ozone-initiated monoterpene reaction products have been hypothesized to cause eye
      and airway complaints in office environments and some have been proposed to cause
      skin irritation and sensitization. The respiratory effects of 60 min exposures to
      five common oxidation products from abundant terpenoids (e.g. limonene), used as
      solvent and fragrance in common household products or present in skin lipids
      (e.g. squalene), were studied in a head out mouse bioassay. This allowed
      determination of acute upper airway (sensory) irritation, airflow limitation in
      the conducting airways, and pulmonary irritation in the alveolar region. Derived
      human reference values (RFs) for sensory irritation were 1.3, 0.16 and 0.3 ppm,
      respectively, for 4-acetyl-1-methylcyclohexene ( 0.2 ppm) [corrected], 3
      isopropenyl-6-oxo-heptanal (IPOH), and 6-methyl-5-heptene-2-one (6-MHO). Derived
      RFs for airflow limitation were 0.8, 0.45, 0.03, and 0.5 ppm, respectively, for
      dihydrocarvone (DHC), 0.2 ppm [corrected], 4-oxo-pentanal (0.3 ppm) [corrected],
      and 6-MHO. Pulmonary irritation was unobserved as a critical effect. The RFs
      indicate that the oxidation products would not contribute substantially to
      sensory irritation in eyes and upper airways in office environments. Reported
      concentrations in offices of 6-MHO and 0.3 ppm [corrected]would not result in
      airflow limitation. However, based upon the RFs for IPOH and 0.3 ppm [corrected],
      precautionary actions should be considered that disfavor their formation in
      excess.

PMID- 23164674
TI  - Early life exposure to air pollution: how bad is it?
AB  - Increasing concentrations of air pollution have been shown to contribute to an
      enormity of adverse health outcomes worldwide, which have been observed in
      clinical, epidemiological, and animal studies as well as in vitro investigations.
      Recently, studies have shown that air pollution can affect the developing fetus
      via maternal exposure, resulting in preterm birth, low birth weight, growth
      restriction, and potentially adverse cardiovascular and respiratory outcomes.
      This review will provide a summary of the harmful effects of air pollution
      exposure on the developing fetus and infant, and suggest potential mechanisms to
      limit the exposure of pregnant mothers and infants to air pollution.

PMID- 23164676
TI  - Percutaneous cerclage wiring, does it disrupt femoral blood supply? A cadaveric
      injection study.
AB  - BACKGROUND: A percutaneous cerclage wiring technique has been developed to reduce
      iatrogenic soft tissue and vascular disruption associated with classic cerclage
      fixation. OBJECTIVES: The purpose of this study was to evaluate the extent of
      femoral vascular disruption resulting iatrogenically from the application of two
      percutaneous cerclage wire loops. METHODS: Pairs of cerlage wire loops were
      percutaneously inserted on 18 fresh cadaveric femurs. The position of the wire
      loops varied. The wire loops were either inserted 10 and 15cm, 10 and 20cm, or 15
      and 20cm distal to the tip of the greater trochanter. Each study group had 6
      cadavers. Contralateral femurs without cerclage wiring were used as controls.
      Liquid contrast-gelatin was injected into the common femoral artery. Using axial
      and 3D CT scan images the superficial femoral artery (SFA), deep femoral artery
      (DFA), perforating arteries and their anastomotic patterns as well as endosteal
      perfusion were identified and their patency was graded. RESULTS: Percutaneous
      cerclage wiring did not disrupt femoral endosteal blood supply and maintained the
      integrity of all of the superficial femoral arteries. Four specimens demonstrated
      maintenance of all 4 perforators, 11 showed disruption of 1 perforator, and 3
      showed disruption of 2 perforators. One deep femoral artery was disrupted after
      its first perforator branched off; however, perfusion was maintained by fill from
      an alternative anastamosis. There was no significant difference between
      disruption of deep femoral arteries and perforating arteries (P=1.000), location
      of wiring (P=0.905) or spacing between wire loops (P=1.000). CONCLUSION:
      Percutaneous cerclage wiring resulted in minimal disruption of the femoral blood
      supply. When partial disruption occurred the SFA, DFA, and their associated
      perforators compensated to maintain femoral perfusion through their anastomoses.
      The location of the cerclage wire and the distance between the wire loops in the
      proximal femur showed no significant difference in the rate of iatrogenic
      perforator injury.

PMID- 23164677
TI  - Introduction to 'steroid hormone actions in the CNS: the role of brain-derived
      neurotrophic factor (BDNF)'.

PMID- 23164678
TI  - Urinary biomarkers for phthalates associated with asthma in Norwegian children.
AB  - BACKGROUND: High-molecular-weight phthalates in indoor dust have been associated
      with asthma in children, but few studies have evaluated phthalate biomarkers in
      association with respiratory outcomes. OBJECTIVES: We explored the association
      between urinary concentrations of phthalate metabolites and current asthma.
      METHODS: In a cross-sectional analysis, 11 metabolites of 8 phthalates [including
      four metabolites of di(2-ethylhexyl) phthalate] were measured in one first
      morning void collected from 2001 through 2004 from 623 10-year-old Norwegian
      children. Logistic regression models controlling for urine specific gravity, sex,
      parental asthma, and income were used to estimate associations between current
      asthma and phthalate metabolite concentrations by quartiles or as log10
      transformed variables. RESULTS: Current asthma was associated with both
      mono(carboxyoctyl) phthalate (MCOP) and mono(carboxynonyl) phthalate (MCNP),
      although the association was limited to those in the highest quartile of these
      chemicals. The adjusted odds ratio (aOR) for current asthma was 1.9 (95% CI: 1.0,
      3.3) for the highest MCOP quartile compared with the lowest quartile, and 1.3
      (95% CI: 0.98, 1.7) for an interquartile-range increase. The aOR for current
      asthma was 2.2 (95% CI: 1.2, 4.0) for the highest MCNP quartile and 1.3 (95% CI:
      1.0, 1.7) for an interquartile-range increase. The other phthalate metabolites
      were not associated with current asthma. CONCLUSIONS: Current asthma was
      associated with the highest quartiles of MCOP and MCNP, metabolites of two high
      molecular weight phthalates, diisononyl phthalate and diisodecyl phthalate,
      respectively. Given the short biological half-life of the phthalates and the
      cross-sectional design, our findings should be interpreted cautiously.

PMID- 23164679
TI  - Thyroid autoimmunity.
AB  - This overview of the thyroid autoimmunity in human presents the various facets of
      a very common pathology. Focus is rather on fundamental than clinical aspects,
      although some specific clinical situations are discussed. Epidemiology,
      pathophysiology and pathology of AITD are detailed. One of the peculiarities of
      AITD is that they express two opposed phenotypes, hypothyroid thyroiditis and
      hyperthyroid Graves' disease. The latter is characterised by the presence of a
      unique type of autoantibodies, the anti-TSH receptor antibodies. Those are
      capable to activate the TSH receptor leading to the gland hypertrophy and
      hyperfunction. On the contrary, the autoimmune thyroiditis processus
      progressively and slowly tends to the necrosis/apoptosis of thyroid cells and
      their functional impairment. Other forms of autoimmune thyroiditis, postpartum
      thyroiditis and silent thyroiditis are also described. This review, which is not
      exhaustive, aims at providing a wide scope on the AITD, a basis from which the
      interested reader or the specialist will be able to find routes towards deeper
      knowledge.

PMID- 23164680
TI  - Electrochemical and phylogenetic analyses of current-generating microorganisms in
      a thermophilic microbial fuel cell.
AB  - To explore diversity of thermophilic exoelectrogens, a thermophilic microbial
      fuel cell was constructed. Population analysis of the anodic microorganisms
      suggested possible involvement of Caloramator-related bacteria in electricity
      generation. Pure culture of Caloramator australicus showed electricity-generating
      ability, indicating that the bacterium is a new thermophilic exoelectrogen.

PMID- 23164681
TI  - Recent progress in biocatalysis using supercritical carbon dioxide.
AB  - The latest advances in biocatalysis using supercritical carbon dioxide (scCO(2))
      are reviewed. Stability and stabilization methodologies of enzymes in scCO(2) as
      well as reactions for organic synthesis are described. Especially, varieties of
      examples for lipase-catalyzed synthesis of chiral compounds using scCO(2) are
      given. Furthermore, asymmetric reduction by alcohol dehydrogenase in scCO(2) and
      carboxylation by decarboxylase in scCO(2) are also introduced.

PMID- 23164682
TI  - Effect of gallic acid on peptides released by trypsin digestion of bovine alpha
      casein.
AB  - In this study, the effects of gallic acid (GA) on trypsin digestion of commercial
      alpha-casein (alpha-CN), which contains alpha(s1)-CN and alpha(s2)-CN, and the
      peptides released during digestion were investigated. Gallic acid showed no
      effect on the initial rate of digestion. However, the apparent degree of
      hydrolysis achieved its maximum value after 1 h, then decreased in the presence
      of GA, suggesting the cross-linking between peptides once released from alpha-CN
      during digestion. In the presence of GA, three peaks derived from alpha(s1)-CN
      disappeared and three new peaks appeared in high-performance liquid
      chromatography (HPLC) analysis. In these peptides, two Met residues corresponding
      to the Met(135) and Met(196) in alpha(s1)-CN were oxidized to Met sulfoxide
      residues. The oxidation of Met(196) was quicker than that of Met(135). The
      inhibitory activity of TTMPLW (alpha(s1)-CN 193-199) against angiotensin I
      converting enzyme was reduced slightly by the oxidation of its Met residue.

PMID- 23164683
TI  - Bevacizumab as rescue treatment for severe recurrent gastrointestinal bleeding in
      hereditary hemorrhagic telangiectasia.
AB  - Hereditary hemorrhagic telangiectasia (HHT) also known as Rendu Osler syndrome is
      a vascular hereditary autosomal dominant disease, leading to a dysfunction in the
      development of arteriovenous capillaries, usually resulting in epistaxis,
      gastrointestinal (GI) bleeding, and iron deficiency anemia. It is believed that
      by interfering and stopping angiogenesis, anti-vascular endothelial growth factor
      molecules could be an option for HHT patients. Indeed, an intranasal treatment
      regime of diluted Avastin (bevacizumab; recombinant humanized antivascular
      epithelial growth factor immunoglobin G1) has proven clinically efficacious in
      patients with HHT1. However, there are no data available regarding bevacizumab's
      effect in patients with HHT and GI bleeding. We report here the case of an 85
      year-old woman, suffering from life-threatening GI bleeding due to HHT with an
      impressive clinical response using anti-vascular endothelial growth factor
      infusion.

PMID- 23164684
TI  - Mucin function in inflammatory bowel disease: an update.
AB  - MUC2 is the primary component of the mucin barrier that separates the intestinal
      microbiota and the intestinal epithelium. This mucous barrier is affected by both
      luminal/microbial factors and host/immune factors, both of which have genetic and
      environmental determinants. The complex interactions between these players in
      health and disease states are not fully understood. Inflammatory bowel disease
      (IBD) has both genetic and environmental etiologies that lead to the breakdown of
      the epithelial barrier. In this review, we explore the up-to-date evidence that
      implicates mucin in the pathogenesis of IBD. In IBD, quantitative changes in
      mucin secretion occur, as well as structural changes in mucin's glycoprotein core
      and the sulfation and sialylation of mucin's oligosaccharide residues. These
      changes are associated with a diminished functionality of the mucous barrier. We
      identify the various genetic mutations associated with these changes and outline
      the animal models that have enhanced the current understanding of the genetic
      basis for IBD. Further study is needed to better characterize the immune and
      genetic influences on mucin expression and secretion and role of endoplasmic
      reticulum stress and a defective unfolded protein response in mediating these
      changes.

PMID- 23164685
TI  - Alcohol consumption is a risk factor for colonic diverticulosis.
AB  - BACKGROUND AND AIM: The exact factors predisposing to colonic diverticulosis
      other than age are unknown. METHODS: Cross-sectional study of asymptomatic
      subjects undergoing screening colonoscopy. A detailed dietary and social
      questionnaire was completed on all participants. A worldwide review of the
      literature was performed to further investigate any association between
      identified risk factors and diverticulosis. RESULTS: Seven hundred forty-six
      consecutive individuals were enrolled (mean age, 61.1+/-8.3 y; female:
      male=0.98). Overall, the prevalence of diverticulosis was 32.8% (95% CI, 29.5
      36.2). Diverticula were left-sided, right-sided, or both in 71.5%, 5.8%, and
      22.7% of affected subjects, respectively. On univariate analysis, age, sex,
      adenomatous polyps, advanced neoplasia (adenoma>=1 cm, villous histology, or
      cancer), aspirin, and alcohol use were significantly associated with
      diverticulosis. Diet, body mass index, physical activity, and bowel habits were
      not associated with the disease. On multivariate analysis, increasing age
      (P<0.001), advanced neoplasia (P=0.021), and alcohol consumption (P<0.001) were
      significantly associated with diverticulosis. The adjusted odds ratio for
      diverticulosis in alcohol users was 1.91 (1.36 to 2.69), with increasing
      prevalence with higher alcohol consumption (P-value for trend=0.001). When the
      prevalence of diverticulosis reported from 18 countries was analyzed against
      alcohol use, there was a strong correlation with national per-capita alcohol
      consumption rates (Pearson correlation coefficient r=0.68; P=0.002). CONCLUSIONS:
      Alcohol use is a significant risk factor for colonic diverticulosis and may offer
      a partial explanation for the existing East-West paradox in disease prevalence
      and phenotype. Further studies are needed to investigate this association and its
      putative pathophysiological mechanisms.

PMID- 23164686
TI  - Video capsule endoscopy in patients with nonresponsive celiac disease.
AB  - GOALS AND BACKGROUND: Discriminating between patients with nonresponsive but
      otherwise uncomplicated celiac disease (CD) and patients with refractory celiac
      disease (RCD) and/or lymphoma is difficult, especially as many abnormalities
      encountered in complicated CD are not within reach of conventional
      gastroduodenoscopy. We aimed to describe video capsule endoscopy (VCE) findings
      in patients with CD and persisting or relapsing symptoms despite a gluten-free
      diet and to identify VCE findings associated with poor prognosis. METHODS: We
      retrospectively analyzed 48 VCE studies performed in adult patients with CD
      because of persisting or relapsing symptoms despite adherence to a gluten-free
      diet. Patients with either uncomplicated CD or RCD type I were considered to have
      a good prognosis, whereas patients with either RCD type II or enteropathy
      associated T-cell lymphoma were considered to have a poor prognosis. Multivariate
      analysis was performed to identify VCE findings independently associated with
      either good or poor prognosis. RESULTS: Proximal focal erythema (odds ratio, 6.7;
      95% confidence interval, 1.2-38.7; P=0.033) and absence of progression of the
      capsule to the distal intestine (odds ratio, 16.5; 95% confidence interval, 1.2
      224.9; P=0.035) were independently associated with poor prognosis. Of the 28
      patients with none of these 2 features, none died during follow-up, compared with
      2 (13.3%) of the 15 patients with one of both features, and 4 (80.0%) of the 5
      patients with both the features. CONCLUSIONS: VCE is a minimally invasive
      endoscopic modality that could be of use in identifying patients with
      nonresponsive CD who are at risk of poor prognosis.

PMID- 23164687
TI  - Diurnal variation in serum alanine aminotransferase activity in the US
      population.
AB  - GOALS AND BACKGROUND: Serum alanine aminotransferase (ALT) activity has been
      reported to be greater in the afternoon than the early morning, but data are
      scarce. We examined diurnal variation of ALT in a national population-based
      sample. STUDY: Participants in the 1999 to 2008 US National Health and Nutrition
      Examination Survey were randomly assigned to morning (AM; n = 4474 adolescents,
      11,235 adults) or afternoon/evening (PM; n = 4887 adolescents, 11,735 adults)
      examinations. We examined ALT distributions graphically and compared both
      geometric mean ALT and the prevalence of elevated ALT, defined as >31 IU/L for
      adolescent boys, >24 IU/L for adolescent girls, >43 IU/L for adult men, and >30
      IU/L for adult women, between AM and PM examination groups. RESULTS: The
      examination groups were similar with the exception in the AM group of a longer
      fasting time and slightly higher prevalence of diabetes among adolescents and
      viral hepatitis B among adult women. ALT distributions were similar between
      examination sessions among the 4 groups. Among adolescents and men, neither mean
      ALT nor prevalence of abnormal ALT differed by examination group. Among women,
      mean ALT was statistically significant, but minimally higher in the PM group
      (19.6 IU/L) than the AM group (19.1 IU/L; P = 0.009). Among 1 subgroup, women
      with chronic viral hepatitis, there was a higher prevalence of abnormal ALT in
      the PM group (P = 0.018 in unadjusted analysis). Adjusting for liver injury risk
      factors had little effect on the difference in mean ALT. CONCLUSIONS: In general,
      clinically significant diurnal variation in ALT activity was not found in the US
      population.

PMID- 23164688
TI  - Seasonal distribution and eosinophilic esophagitis:  the experience in children
      living in rural communities.

PMID- 23164689
TI  - Significance of proton pump inhibitor types for Clostridium difficile infection.

PMID- 23164690
TI  - Orally bioavailable small molecule drug protects memory in Alzheimer's disease
      models.
AB  - Oligomers of beta-amyloid (Abeta) are implicated in the early memory impairment
      seen in Alzheimer's disease before to the onset of discernable neurodegeneration.
      Here, the capacity of a novel orally bioavailable, central nervous system
      penetrating small molecule 5-aryloxypyrimidine, SEN1500, to prevent cell-derived
      (7PA2 [conditioned medium] CM) Abeta-induced deficits in synaptic plasticity and
      learned behavior was assessed. Biochemically, SEN1500 bound to Abeta monomer and
      oligomers, produced a reduction in thioflavin-T fluorescence, and protected a
      neuronal cell line and primary cortical neurons exposed to synthetic soluble
      oligomeric Abeta(1-42). Electrophysiologically, SEN1500 alleviated the in vitro
      depression of long-term potentiation induced by both synthetic Abeta(1-42) and
      7PA2 CM, and alleviated the in vivo depression of long-term potentiation induced
      by 7PA2 CM, after systemic administration. Behaviorally, oral administration of
      SEN1500 significantly reduced memory-related deficits in operant responding
      induced after intracerebroventricular injection of 7PA2 CM. SEN1500 reduced
      cytotoxicity, acute synaptotoxicity, and behavioral deterioration after in vitro
      and in vivo exposure to synthetic Abeta and 7PA2 CM, and shows promise for
      development as a clinically viable disease-modifying Alzheimer's disease
      treatment.

PMID- 23164691
TI  - Isobavachalcone suppresses expression of inducible nitric oxide synthase induced
      by Toll-like receptor agonists.
AB  - Toll-like receptors (TLRs) play an important role by recognizing many pathogen
      associated molecular patterns and inducing innate immunity. Dysregulated
      activation of TLR signaling pathways induces the activation of various
      transcription factors such as nuclear factor-kappaB, leading to the induction of
      pro-inflammatory gene products such as inducible nitric oxide synthase (iNOS).
      The present study investigated the effect of isobavachalcone (IBC), a natural
      chalcone component of Angelica keiskei, on inflammation by modulating iNOS
      expression induced by TLR agonists in murine macrophages. IBC suppressed iNOS
      expression induced by macrophage-activating lipopeptide 2-kDa, polyriboinosinic
      polyribocytidylic acid, or lipopolysaccharide. These results indicate the
      potential of IBC as a potent anti-inflammatory drug.

PMID- 23164692
TI  - LAFARA: a new underground laboratory in the French Pyrenees for ultra low-level
      gamma-ray spectrometry.
AB  - We describe a new underground laboratory, namely LAFARA (for "LAboratoire de
      mesure des FAibles RAdioactivites"), that was recently created in the French
      Pyrenees. This laboratory is primarily designed to analyze environmental samples
      that display low radioactivity levels using gamma-ray spectrometry. Two high
      purity germanium detectors were placed under 85 m of rock (ca. 215 m water
      equivalent) in the tunnel of Ferrieres (Ariege, France). The background is thus
      reduced by a factor of ~20 in comparison to above-ground laboratories. Both
      detectors are fully equipped so that the samples can be analyzed in an automatic
      mode without requiring permanent presence of a technician in the laboratory. Auto
      samplers (twenty positions) and systems to fill liquid nitrogen automatically
      provide one month of autonomy to the spectrometers. The LAFARA facility allows us
      to develop new applications in the field of environmental sciences based on the
      use of natural radionuclides present at low levels in the environment. As an
      illustration, we present two of these applications: i) dating of marine sediments
      using the decay of (226)Ra in sedimentary barite (BaSO(4)), ii) determination of
      (227)Ac ((231)Pa) activities in marine sediment cores.

PMID- 23164693
TI  - Soil and building material as main sources of indoor radon in Baita-Stei radon
      prone area (Romania).
AB  - Radon contributes to over than 50% of the natural radiation dose received by
      people. In radon risk areas this contribution can be as high as 90-95%, leading
      to an exposure to natural radiation 5-10 times higher than normal. This work
      presents results from radon measurements (indoor, soil and exhalation from
      building materials) in Baita-Stei, a former uranium exploitation area in NW
      Romania. In this region, indoor radon concentrations found were as high as 5000
      Bq m(-3) and soil radon levels ranged from 20 to 500 kBq m(-3). An important
      contribution from building materials to indoor radon was also observed. Our
      results indicate two independent sources of indoor radon in the surveyed houses
      of this region. One source is coming from the soil and regular building
      materials, and the second source being uranium waste and local radium reached
      material used in building construction. The soil as source of indoor radon shows
      high radon potential in 80% of the investigated area. Some local building
      materials reveal high radon exhalation rate (up to 80 mBq kg(-1) h(-1) from a
      sandy-gravel material, ten times higher than normal material). These measurements
      were used for the radon risk classification of this area by combining the radon
      potential of the soil with the additional component from building materials. Our
      results indicate that Baita-Stei area can be categorized as a radon prone area.

PMID- 23164694
TI  - Arrival of radionuclides released by the Fukushima accident to Tenerife (Canary
      Islands).
AB  - Two weeks after the accident at the Fukushima-Daichi nuclear power plant, 131I,
      137Cs and 134Cs activities were measured in two different stations located in
      Tenerife (Canary Islands), situated at 300 (FIMERALL) and 2400 (IZANA) m.a.s.l,
      respectively. Peak measured activity concentrations were: 1.851 mBq/m3 (131I);
      0.408 mBq/m3 (137Cs) and 0.382 mBq/m3 (134Cs). The activities measured at the
      FIMERALL station were always higher than at IZANA station, suggesting that the
      radioactive plume arrived to the island associated with low altitude air masses.
      Simulations of potential dispersion of the radioactive cloud (137Cs) after the
      nuclear accident in reactor Fukushima I show that radioactive pollution reached
      remote regions such as the Canary Islands in the Eastern subtropical North
      Atlantic. The corresponding effective dose to the local population was 1.17 nSv,
      a value less than one millionth of the annual limit for the general public.
      Therefore, there was no risk to public health.

PMID- 23164695
TI  - IL28B rs12979860 polymorphism influences serum TNFalpha levels in chronic
      hepatitis C.

PMID- 23164696
TI  - Comparison of the independent and combined metabolic effects of subchronic
      modulation of CCK and GIP receptor action in obesity-related diabetes.
AB  - OBJECTIVE: Compromise of gastric inhibitory polypeptide (GIP) receptor action and
      activation of cholecystokinin (CCK) receptors represent mechanistically different
      approaches to the possible treatment of obesity-related diabetes. In the present
      study, we have compared the individual and combined effects of (Pro(3))GIP[mPEG]
      and (pGlu-Gln)-CCK-8 as an enzymatically stable GIP receptor antagonist and CCK
      receptor agonist molecule, respectively. RESULTS: Twice-daily injections of (pGlu
      Gln)-CCK-8 alone and in combination with (Pro(3))GIP[mPEG] in high-fat-fed mice
      for 34 days significantly decreased the energy intake throughout the entire study
      (P<0.05 to P<0.01). Body weights were significantly depressed (P<0.05 to P<0.01)
      in all treatment groups from day 18 onwards. Administration of (pGlu-Gln)-CCK-8,
      (Pro(3))GIP[mPEG] or a combination of both peptides significantly (P<0.01 to
      P<0.001) decreased the overall glycaemic excursion in response to both oral and
      intraperitoneal glucose challenge when compared with the controls. Furthermore,
      oral glucose tolerance returned to lean control levels in all treatment groups.
      The beneficial effects on glucose homeostasis were not associated with altered
      insulin levels in any of the treatment groups. In keeping with this, the
      estimated insulin sensitivity was restored to control levels by twice-daily
      treatment with (pGlu-Gln)-CCK-8, (Pro(3))GIP[mPEG] or a combination of both
      peptides. The blood lipid profile on day 34 was not significantly different
      between the high-fat controls and all treated mice. CONCLUSION: These studies
      highlight the potential of (pGlu-Gln)-CCK-8 and (Pro(3))GIP[mPEG] in the
      treatment of obesity-related diabetes, but there was no evidence of a synergistic
      effect of the combined treatment.

PMID- 23164697
TI  - Adolescents bullying and young adults body mass index and obesity: a longitudinal
      study.
AB  - OBJECTIVE: To examine whether adolescent males and females who were victims of
      bullying were at greater risk of a higher body mass index (BMI) and obesity by
      young adulthood. DESIGN: Secondary analysis of data from a community-based cohort
      study. SUBJECTS: A sub-sample of 1694 offspring (50% males) who were participants
      in the Mater-University of Queensland Study of Pregnancy (MUSP), Brisbane, and
      who provided bullying information at 14 years and physical assessment at 21
      years. MAIN OUTCOME MEASURES: BMI and its categories as normal, overweight or
      obese at 21 years. RESULTS: One in two adolescent males and one in three
      adolescent females reported that they had been bullied at school by others. We
      found that adolescent males and females who were bullied were at a significantly
      greater risk of a higher BMI and obesity by young adulthood. Fourteen-year-old
      males who were occasionally/often bullied at school had 0.64 (95% confidence
      interval (CI): 0.02, 1.27) kg m(2) greater mean BMI by 21 years compared with
      males who were never bullied by 14 years. This mean difference in BMI was 1.52,
      (95% CI: 0.75, 2.29) kg m(2) for females. Similarly, the odds of being obese were
      2.54 (95% CI: 1.58, 4.09) times at 21 years for those males who were bullied
      occasionally/often compared with adolescent males who were never bullied. For
      females, this was 2.18 (95% CI: 1.40, 3.39). Overweight adolescents who
      experienced bullying had the greatest increase in BMI by young adulthood.
      Adjusting for potential confounding or mediating factors, the associations remain
      strong for males but are attenuated for females. CONCLUSIONS: The findings of
      this study suggest that both male and female adolescents who were bullied
      often/sometimes by their peer group at 14 years were at greater risk of higher
      BMI and obesity by young adulthood.

PMID- 23164698
TI  - Diet-induced obesity alters the differentiation potential of stem cells isolated
      from bone marrow, adipose tissue and infrapatellar fat pad: the effects of free
      fatty acids.
AB  - INTRODUCTION: Obesity is a major risk factor for several musculoskeletal
      conditions that are characterized by an imbalance of tissue remodeling. Adult
      stem cells are closely associated with the remodeling and potential repair of
      several mesodermally derived tissues such as fat, bone and cartilage. We
      hypothesized that obesity would alter the frequency, proliferation, multipotency
      and immunophenotype of adult stem cells from a variety of tissues. MATERIALS AND
      METHODS: Bone marrow-derived mesenchymal stem cells (MSCs), subcutaneous adipose
      derived stem cells (sqASCs) and infrapatellar fat pad-derived stem cells (IFP
      cells) were isolated from lean and high-fat diet-induced obese mice, and their
      cellular properties were examined. To test the hypothesis that changes in stem
      cell properties were due to the increased systemic levels of free fatty acids
      (FFAs), we further investigated the effects of FFAs on lean stem cells in vitro.
      RESULTS: Obese mice showed a trend toward increased prevalence of MSCs and sqASCs
      in the stromal tissues. While no significant differences in cell proliferation
      were observed in vitro, the differentiation potential of all types of stem cells
      was altered by obesity. MSCs from obese mice demonstrated decreased adipogenic,
      osteogenic and chondrogenic potential. Obese sqASCs and IFP cells showed
      increased adipogenic and osteogenic differentiation, but decreased chondrogenic
      ability. Obese MSCs also showed decreased CD105 and increased platelet-derived
      growth factor receptor alpha expression, consistent with decreased chondrogenic
      potential. FFA treatment of lean stem cells significantly altered their
      multipotency but did not completely recapitulate the properties of obese stem
      cells. CONCLUSIONS: These findings support the hypothesis that obesity alters the
      properties of adult stem cells in a manner that depends on the cell source. These
      effects may be regulated in part by increased levels of FFAs, but may involve
      other obesity-associated cytokines. These findings contribute to our
      understanding of mesenchymal tissue remodeling with obesity, as well as the
      development of autologous stem cell therapies for obese patients.

PMID- 23164699
TI  - A patient-centred approach to estimate total annual healthcare cost by body mass
      index in the UK Counterweight programme.
AB  - BACKGROUND: Previous studies, based on relative risks for certain secondary
      diseases, have shown greater healthcare costs in higher body mass index (BMI)
      categories. The present study quantifies the relationship between BMI and total
      healthcare expenditure, with the patient as the unit of analysis. METHODS:
      Analyses of cross-sectional data, collected over 18-months in 2002-2003, from
      3324 randomly selected patients, in 65 general practices across UK. Healthcare
      costs estimated from primary care, outpatient, accident/emergency and
      hospitalisation attendances, weighted by unit costs taken from standard sources.
      RESULTS: In univariate analyses, significant associations (P<0.05) were found
      between total healthcare expenditure and all dependent variables (women>men,
      drinker<non-drinkers, smokers>non-smokers, and increasing with greater physical
      activity, age and BMI. In multivariate analysis, age, sex, BMI, smoking and
      alcohol consumption remained significantly associated with healthcare cost, and
      together explained just 9% of the variance in healthcare expenditure. Adjusted
      total annual healthcare cost was L16 (95% CI L11-L21) higher per unit BMI. All
      cost categories were significantly (P<0.003) higher for those with BMI >40
      compared with BMI <20 kg m(-2): prescription drugs (men: L390 versus L16; women:
      L211 versus L73), hospitalisation (men: L72 versus L0; women: L243 versus L107),
      primary care (men: L191 versus L69; women: L268 versus L153) and outpatient care
      (L234 versus L107 women only). CONCLUSIONS: Annual healthcare expenditure rose a
      mean of L16 per unit greater BMI, doubling between BMI 20-40 kg m(-2). This
      gradient may be an underestimate if the lower-BMI patients with heights and
      weights recorded had other costly diseases.

PMID- 23164700
TI  - Pubertal timing and adult obesity and cardiometabolic risk in women and men: a
      systematic review and meta-analysis.
AB  - Obesity has complex multifactorial aetiology. It has been suggested by many, but
      not all, reports that earlier pubertal maturation may increase adult obesity
      risk. We conducted a systemic review and meta-analysis in both women and men, and
      hypothesised that any association between pubertal timing and adult obesity is
      likely to be confounded by childhood adiposity. In addition, we investigated
      whether pubertal timing is related to other cardiometabolic risk and long-term
      cardiovascular morbidity/mortality. Literature search was undertaken using
      MEDLINE, EMBASE, Web of Knowledge and TRIP databases, with a hand search of
      references. Both authors independently reviewed and extracted pre-defined data
      from all selected papers. Meta-analyses were conducted using Review Manager
      (RevMan) 5.0.24. A total of 48 papers were identified. Out of 34 studies, 30
      reported an inverse relationship between pubertal timing and adult body mass
      index (BMI), the main adiposity measure used. Meta-analysis of 10 cohorts showed
      association between early menarche (menarche <12 vs >=12 years) and increased
      adult BMI, with a standardised mean difference of 0.34 kg m(-2) (95% confidence
      interval: 0.33-0.34). Heterogeneity was large (I(2)=92%) but reduced
      significantly when grouped by outcome age. Late menarche (menarche >=15 vs <15
      years) was associated with decreased adult BMI, with a standardised mean
      difference of -0.26 kg m(-2) (95% confidence interval: -0.36, -0.21) (seven
      cohorts). Only eight papers included data on childhood BMI; the majority reported
      that childhood BMI only partially attenuated association between early menarche
      and later obesity. Although not suitable for meta-analysis, data on
      cardiometabolic risk factors and puberty suggested negative association between
      earlier pubertal timing and cardiovascular mortality, hypertension, metabolic
      syndrome (MetS) and abnormal glycaemia. Earlier pubertal timing is predictive of
      higher adult BMI and greater risk of obesity. This effect appears to be partially
      independent of childhood BMI. Earlier pubertal development appears to also be
      inversely correlated with risk of other cardiometabolic risk factors and
      cardiovascular mortality. Further work is needed to examine potential mechanisms
      and the level at which interventions may be targeted.

PMID- 23164703
TI  - Relationship between surface properties determined by inverse gas chromatography
      and ibuprofen release from hybrid materials based on fumed silica.
AB  - The ability of organic-inorganic hybrid materials to act as drug release
      modifying agents was examined. In this study, ibuprofen, a non-steroidal anti
      inflammatory drug was used as a model active pharmaceutical ingredient. The
      physicochemical properties of individual components of the hybrids, as well as
      these for two- and three-component systems were examined by inverse gas
      chromatography. The dispersive component of the free surface energy
      (gamma(S)(D)), K(A) and K(D) parameters describing acidity and basicity of hybrid
      materials, respectively, as well as Flory-Huggins parameters were determined.
      chi(12)(infinity) and [Formula: see text] parameters characterize the
      interactions between the hybrids and a test solute, or interactions between the
      drug and inorganic-organic materials, respectively. Additionally, Brunauer-Emmett
      Teller (BET) method was used to characterize adsorption activity of the studied
      materials. The prepared hybrid materials were also characterized by Fourier
      transform infra-red (FTIR) spectroscopy. The release profiles of ibuprofen for
      the created hybrid materials were determined. Relationship between the
      physicochemical activity of hybrid materials and ibuprofen release was presented
      and discussed.

PMID- 23164701
TI  - Diet-induced obesity: dopamine transporter function, impulsivity and motivation.
AB  - OBJECTIVE: A rat model of diet-induced obesity (DIO) was used to determine
      dopamine transporter (DAT) function, impulsivity and motivation as
      neurobehavioral outcomes and predictors of obesity. DESIGN: To evaluate
      neurobehavioral alterations following the development of DIO induced by an 8-week
      high-fat diet (HF) exposure, striatal D2-receptor density, DAT function and
      expression, extracellular dopamine concentrations, impulsivity, and motivation
      for high- and low-fat reinforcers were determined. To determine predictors of
      DIO, neurobehavioral antecedents including impulsivity, motivation for high-fat
      reinforcers, DAT function and extracellular dopamine were evaluated before the 8
      week HF exposure. METHODS: Striatal D2-receptor density was determined by in
      vitro kinetic analysis of [(3)H]raclopride binding. DAT function was determined
      using in vitro kinetic analysis of [(3)H]dopamine uptake, methamphetamine-evoked
      [(3)H]dopamine overflow and no-net flux in vivo microdialysis. DAT cell-surface
      expression was determined using biotinylation and western blotting. Impulsivity
      and food-motivated behavior were determined using a delay discounting task and
      progressive ratio schedule, respectively. RESULTS: Relative to obesity-resistant
      (OR) rats, obesity-prone (OP) rats exhibited 18% greater body weight following an
      8-week HF-diet exposure, 42% lower striatal D2-receptor density, 30% lower total
      DAT expression, 40% lower in vitro and in vivo DAT function, 45% greater
      extracellular dopamine and twofold greater methamphetamine-evoked [(3)H]dopamine
      overflow. OP rats exhibited higher motivation for food, and surprisingly, were
      less impulsive relative to OR rats. Impulsivity, in vivo DAT function and
      extracellular dopamine concentration did not predict DIO. Importantly, motivation
      for high-fat reinforcers predicted the development of DIO. CONCLUSION: Human
      studies are limited by their ability to determine if impulsivity, motivation and
      DAT function are causes or consequences of DIO. The current animal model shows
      that motivation for high-fat food, but not impulsive behavior, predicts the
      development of obesity, whereas decreases in striatal DAT function are exhibited
      only after the development of obesity.

PMID- 23164702
TI  - Effects of fruit and vegetable, consumed in solid vs beverage forms, on acute and
      chronic appetitive responses in lean and obese adults.
AB  - BACKGROUND: The effects of fruits and vegetables in solid vs beverage forms on
      human appetite and food intake, acutely and chronically, are unclear. METHODS:
      This 21-week, randomized, crossover study assessed appetitive ratings following
      the inclusion of fruits and vegetables, in solid and beverage form, into the
      habitual diet of healthy lean (n=15) and overweight/obese (n=19) adults with low
      customary consumption. The primary acute outcomes were satiation (amount of
      challenge meal consumed), satiety (latency of subsequent eating event) and
      dietary compensation after a 400 kcal fruit preload. Ratings of appetite were
      also obtained before and after 8 weeks of required increased fruit and vegetable
      consumption (20% estimated energy requirement). RESULTS: Acutely,
      overweight/obese participants reported smaller reductions of hunger after
      consuming the fruit preload in beverage compared with solid form (preload * form
      * body mass index effects, P=0.03). Participants also consumed significantly less
      of a challenge meal (in both gram and energy) after the ingestion of the solid
      fruit preload (P<0.005). However, the subsequent meal latency was not
      significantly different between the solid and the beverage fruit preloads. Total
      daily energy intake was significantly higher when the obese participants consumed
      the beverage fruit preload compared with the solid (P<0.001). Daily energy intake
      was markedly, but not significantly, higher among the lean with the beverage vs
      solid food form. Hunger and fullness ratings remained stable when participants
      consumed fruits and vegetables in solid or beverage form for 8 weeks each.
      CONCLUSION: Acute post-ingestive appetitive responses were weaker following
      consumption of fruits in beverage vs solid food forms. Consumption of beverage or
      solid fruit and vegetable food loads for 8 weeks did not chronically alter
      appetitive responses.

PMID- 23164704
TI  - Technology of stable, prolonged-release eye-drops containing Cyclosporine A,
      distributed between lipid matrix and surface of the solid lipid microspheres
      (SLM).
AB  - The aim of this study was to prepare solid lipid microspheres (SLM) with
      incorporated Cyclosporine A (Cs), suitable for ocular application. For this
      purpose, SLM were formulated by using different lipids and three different
      nonionic surfactants. The SLM were produced using a hot emulsification method.
      The SLM dispersions contained 10, 20 or 30% of lipid (w/w) and up to 2% (w/w) of
      Cs. The size of the microspheres with Cs ranged from 1 to 15 MUm. Physically
      stable SLM with Cs were prepared using Compritol, as a lipid matrix, and Tween
      80, as a surfactant. In contrast, dispersion with Precirol alone, formed semi
      solid gels during storage, while in formulations with Precirol and Miglyol,
      crystals of Cs were observed. In vitro release profile of Compritol formulations
      showed that 40% of Cs is released within 1h, while the release of the following
      40% takes more time, depending on lipid content in the formulations. The large
      part of Cs, added to SLM formulations (from 45 to 80%), was found on the surface
      of microparticles, but no drug crystallization occurred during a long-term
      storage.

PMID- 23164705
TI  - Selection of PLA polymers for the development of injectable prilocaine controlled
      release microparticles: usefulness of thermal analysis.
AB  - The use of injectable local anaesthetics for the treatment of severe
      postoperative pain is limited by the short duration of the painkilling effect.
      Pre-formulation studies were carried out for the development of an injectable
      microparticle formulation for controlled release of prilocaine, an amino-amide
      type local anaesthetic suitable for intravenous, subcutaneous and intramuscular
      administration. To the best of our knowledge, the encapsulation of prilocaine
      into microparticles has not been investigated yet. Three different poly-lactic
      acid (PLA) polymers were separately employed for the preparation of the
      microparticles. Thermal analyses by differential scanning calorimetry (DSC) were
      carried out for the characterization of the raw materials, to assess the drug
      polymer compatibility and miscibility, to investigate the effects of the
      production process on the components. Empty and prilocaine loaded microparticles
      were prepared by double emulsion method. All formulations were fully
      characterized in terms of drug content, morphology, size and in vitro drug
      release. The preliminary value of PRL solubility in the polymer material
      determined by DSC was evaluated and discussed as a predictive value for
      encapsulation efficiency and controlled release. DSC analysis turned out to be a
      usefulness tool for a fast polymer selection. Microparticles prepared with PLA
      R202 and R203S showed desirable characteristics for subcutaneous administration
      and could represent two promising formulations for the development of innovative
      pharmacological tools in the treatment of postoperative pain.

PMID- 23164707
TI  - Synthesis and antibacterial activity of novel water-soluble nocathiacin analogs.
AB  - Semi-synthetic water-soluble analogs were synthesized from nocathiacin I through
      the formation of a versatile intermediate nocathiacin amine 5, and subsequent
      transformation via reductive amination, acylation or urea formation. Several of
      the novel analogs displayed much improved aqueous solubility over 1, while
      retained antibacterial activity. Compound 15 and 16 from the amide series,
      demonstrated excellent in vitro and in vivo antibacterial activity.

PMID- 23164706
TI  - Identification of inhibitors against interaction between pro-inflammatory sPLA2
      IIA protein and integrin alphavbeta3.
AB  - Increased concentrations of secreted phospholipase A2 type IIA (sPLA2-IIA), have
      been found in the synovial fluid of patients with rheumatoid arthritis. It has
      been shown that sPLA2-IIA specifically binds to integrin alphavbeta3, and
      initiates a signaling pathway that leads to cell proliferation and inflammation.
      Therefore, the interaction between integrin and sPLA2-IIA could be a potential
      therapeutic target for the treatment of proliferation or inflammation-related
      diseases. Two one-bead-one-compound peptide libraries were constructed and
      screened, and seven target hits were identified. Herein we report the
      identification, synthesis, and biological testing of two pyrazolylthiazole
      tethered peptide hits and their analogs. Biological assays showed that these
      compounds were able to suppress the sPLA2-IIA-integrin interaction and sPLA2-IIA
      induced migration of monocytic cells and that the blockade of the sPLA2-IIA
      integrin binding was specific to sPLA2-IIA and not to the integrin.

PMID- 23164708
TI  - Heat-initiated detection for reduced glutathione with 19F NMR probes based on
      modified gold nanoparticles.
AB  - For detecting reduced glutathione (GSH) with a (19)F NMR spectroscopy with time
      specificity, we developed the probes based on gold nanoparticles modified with
      the fluorinated groups via the thermally-cleavable linkers. Before the heating
      treatment with the probe, the maleimide moiety as a binding site with GSH in the
      probe is inactivated by cycloaddition of furan. At this silent state, the
      magnitude of (19)F NMR signals from the fluorinated groups was suppressed. By
      heating for the activation of the probe, the maleimide moiety was produced via
      retro Diels-Alder reaction, and (19)F NMR signals were observed. From this
      moment, GSH started the reaction with the probe via Michael addition to the
      maleimide moiety, leading to the observation of the new peak in (19)F NMR
      spectra. Finally, the amounts of GSH were determined from the increase of the
      magnitude of (19)F NMR signals.

PMID- 23164709
TI  - Xanthone derivatives as potential inhibitors of miRNA processing by human Dicer:
      targeting secondary structures of pre-miRNA by small molecules.
AB  - In recent years, various biological processes have been found to be regulated by
      miRNA-mediated gene silencing. A small molecule that modulate the miRNA pathway
      will provide the biological tool for elucidating mechanisms of miRNA-mediated
      gene regulation, and can be the drug lead for miRNA related diseases. In this
      study, we demonstrated that an aminoalkoxy-substituted thioxanthone derivative
      interferes Dicer-mediated processing of pre-miRNA. Information about the
      interaction between these xanthone derivatives and pre-miRNAs will enable us to
      design and develop new small molecule-based inhibitors for miRNA pathway.

PMID- 23164710
TI  - Venezuelines A-G, new phenoxazine-based alkaloids and aminophenols from
      Streptomyces venezuelae and the regulation of gene target Nur77.
AB  - Five new phenoxazine-based alkaloids venezuelines A-E (1-5) and two new
      aminophenols venezuelines F-G (6-7), as well as three known analogues
      exfoliazone, chandrananimycin D and carboxyexfoliazone were isolated from the
      fermentation broth of the marine-derived bacterium Streptomyces venezuelae. The
      structures of new compounds were determined on the basis of extensive
      spectroscopic analysis. The cytotoxic activity of these compounds against a panel
      of tumor cell lines were tested, while the regulation of gene target Nur77 of 2
      and exfoliazone (8) were evaluated.

PMID- 23164711
TI  - On scaffold hopping: challenges in the discovery of sulfated small molecules as
      mimetics of glycosaminoglycans.
AB  - The design of sulfated, small, nonsaccharide molecules as modulators of proteins
      is still in its infancy as standard drug discovery tools such as library of
      diverse sulfated molecules and in silico docking and scoring protocol have not
      been firmly established. Databases, such as ZINC, contain too few sulfate
      containing nonsaccharide molecules, which severely limits the identification of
      new hits. Lack of a generally applicable protocol for scaffold hopping limits the
      development of sulfated small molecules as synthetic mimetics of the highly
      sulfated glycosaminoglycans. We explored a sequential ligand-based (LBVS) and
      structure-based virtual screening (SBVS) approach starting from our initial
      discovery of monosulfated benzofurans to discover alternative scaffolds as
      allosteric modulators of thrombin, a key coagulation enzyme. Screening the ZINC
      database containing nearly 1 million nonsulfated small molecules using a
      pharmacophore developed from the parent sulfated benzofurans followed by a
      genetic algorithm-based dual-filter docking and scoring screening identified a
      group of 10 promising hits, of which three top-scoring hits were synthesized.
      Each was found to selectively inhibit human alpha-thrombin suggesting the
      possibility of this approach for scaffold hopping. Michaelis-Menten kinetics
      showed allosteric inhibition mechanism for the best molecule and human plasma
      studies confirmed good anticoagulation potential as expected. Our simple
      sequential LBVS and SBVS approach is likely to be useful as a general strategy
      for identification of sulfated small molecules hits as modulators of
      glycosaminoglycan-protein interactions.

PMID- 23164712
TI  - Synthesis and antiplasmodial activity of some 1-azabenzanthrone derivatives.
AB  - Some synthetic 1-azabenzanthrones (7H-dibenzo[de,h]quinolin-7-ones) are weakly to
      moderately cytotoxic, suggesting that they might also show antiparasitic
      activity. We have now tested a small collection of these compounds in vitro
      against a chloroquine-resistant Plasmodium falciparum strain, comparing their
      cytotoxicity against normal human fibroblasts. Our results indicate that 5
      methoxy-1-azabenzanthrone and its 2,3-dihydro analogue have low micromolar
      antiplasmodial activities and showed more than 10-fold selectivity against the
      parasite, indicating that the dihydro compound, in particular, might serve as a
      lead compound for further development.

PMID- 23164713
TI  - Enantioselective synthesis of derivatives and structure-activity relationship
      study in the development of NA255 as a novel host-targeting anti-HCV agent.
AB  - Hepatitis C virus (HCV) infection represents a serious health-care problem.
      Previously we reported the identification of NA255 from our natural products
      library using a HCV sub-genomic replicon cell culture system. Herein, we report
      how the absolute stereochemistry of NA255 was determined and an enantioselective
      synthetic method for NA255 derivatives was developed. The structure-activity
      relationship of the NA255 derivatives and rat pharmacokinetic profiles of the
      representative compounds are disclosed.

PMID- 23164714
TI  - Molecular cloning and antifibrinolytic activity of a serine protease inhibitor
      from bumblebee (Bombus terrestris) venom.
AB  - Bumblebee (Bombus spp.) venom contains a variety of components, including
      bombolitin, phospholipase A(2) (PLA(2)), serine proteases, and serine protease
      inhibitors. In this study, we identified a bumblebee (Bombus terrestris) venom
      serine protease inhibitor (Bt-KTI) that acts as a plasmin inhibitor. Bt-KTI
      consists of a 58-amino acid mature peptide that displays features consistent with
      snake venom Kunitz-type inhibitors, including six conserved cysteine residues and
      a P1 site. Recombinant Bt-KTI was expressed as a 6.5-kDa peptide in baculovirus
      infected insect cells. The recombinant peptide demonstrated properties similar to
      Kunitz-type trypsin inhibitors. Bt-KTI showed no detectable inhibitory effects on
      factor Xa, thrombin, or tissue plasminogen activator; however, Bt-KTI strongly
      inhibited plasmin, indicating that it acts as an antifibrinolytic agent. These
      findings demonstrate the antifibrinolytic role of Bt-KTI as a plasmin inhibitor.

PMID- 23164715
TI  - Raloxifene, arterial function and Ockham's razor.

PMID- 23164716
TI  - Carboplatin delays mammary cancer 4T1 growth in mice.
AB  - Carboplatin is commonly used to treat a variety of tumors. We investigated the
      effects of carboplatin (100mg/kg) in the development and metastatic dissemination
      of the 4T1 mice mammary carcinoma. Carboplatin was able to reduce tumor volume
      and the number of lung metastases in 50% compared to the control animals. Mitotic
      and apoptotic indices were also decreased by the treatment. Assessment of the
      vascularization of the tumors revealed a significant decrease in blood vessel
      formation by carboplatin. A decrease in nuclear positivity of CDC47 and cyclin D1
      was observed in the group treated with carboplatin when compared to the control
      group. Positivity for p53 was observed in the control group (2/28; 5%) and the
      treated group (5/71; 4%). Carboplatin has been demonstrated to be an efficient
      regulator of 4T1MMT growth and dissemination. The action of this chemotherapeutic
      agent seems to be related to the induction of apoptosis and inhibition of
      angiogenesis and cell proliferation.

PMID- 23164717
TI  - Osteogenic differentiation of bone marrow mesenchymal stem cells of
      ovariectomized and non-ovariectomized female rats with thyroid dysfunction.
AB  - The objective of this study was to verify the osteogenic potential of the bone
      marrow mesenchymal stem cells (MSCs) of ovariectomized and non-ovariectomized
      female rats with hypo- and hyperthyroidism. Sixty two-month-old female rats were
      assigned to the following groups: (1) control (sham-operated), (2) ovariectomized
      (OVX'd), (3) hypothyroid sham-operated (Hypo-), (4) hypothyroid OVX'd, (5)
      hyperthyroid sham-operated (Hyper-) and (6) hyperthyroid OVX'd. After 135 days of
      treatment, the female rats were euthanized. We collected plasma to measure the
      levels of free T4, and the femur for extraction of MSCs. At 7 and 21 days of
      osteogenic differentiation of MSCs, 3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide (MTT) conversion, alkaline phosphatase activity,
      mineralized nodule number and gene expression for collagen I, osteocalcin, bone
      sialoprotein and osteopontin were analyzed. The hypothyroid group presented a
      significant reduction in the osteogenic differentiation of MSCs. The hyperthyroid
      group did not present changes in the synthesis of mineralized nodules for MSCs at
      day 21 of differentiation. However, in ovariectomized rats, hyperthyroidism
      increased the osteogenic differentiation of MSCs characterized by the increase of
      the alkaline phosphatase activity, the number of mineralized nodules and the
      expression of osteocalcin, sialoprotein and osteopontin. Our results demonstrated
      that the hypothyroidism reduces the osteogenic differentiation of MSCs only in
      non-ovariectomized rats and that the hyperthyroidism increases the osteogenic
      differentiation of MSCs only in ovariectomized rats.

PMID- 23164718
TI  - MSI1 overexpression in diffuse type of gastric cancer.
AB  - Being the third most frequent cause of cancer mortality in the world, gastric
      cancer is the major cause of cancer-related mortality in Iran. Musashi1
      recognizes a motif in the 3'UTR of target mRNAs - involved in cell cycle
      regulation, proliferation and apoptosis - and represses the translation of the
      mRNAs. As tissue stem cells exist in many adult tissues other than the CNS,
      Musashi is considered to be associated with many malignancies. In the current
      study, we aimed to assess Musashi1 gene expression in human stomach cancer. In
      total, 30 paired gastric tumoral and adjacent non-tumoral tissue specimens were
      examined for gene expression by qReal-Time RT-PCR. Our results demonstrated that
      the expression of the gene did not significantly change between tumor/non-tumor
      tissues (p value: 16*10(-2)) and different grades (p value: 36*10(-2)). However,
      there was a statistical difference between the MSI1 gene expression in different
      tumor types, i.e., intestinal versus diffuse type (p value: 3*10(-2)). All
      together, further investigations should be done to elucidate the precise
      molecular mechanisms by which MSI1 contribute to the pathogenesis of gastric
      cancer.

PMID- 23164719
TI  - Perspective of family caregivers on self-care independence among older people
      living in long-term care facilities: a qualitative study.
AB  - BACKGROUND: Long-term care facilities have difficulty facilitating elders'
      independent self-care. Promoting self-care independence among residents of long
      term care facilities cannot be ignored and needs to be further understood.
      OBJECTIVES: To investigate how family caregivers' perceived building self-care
      independence among elders living in long-term care facilities. DESIGN: This study
      used a qualitative descriptive approach. The data were collected through face-to
      face interviews with 44 elders' family caregivers. SETTINGS: The data was
      collected from family caregivers of elders living in long-term care facilities in
      southern Taiwan. PARTICIPANTS: Eligibility criteria for family-caregivers were:
      (1) residents' family members living in community settings, (2) able to speak
      Mandarin or Taiwanese, (3) willing to be tape-recorded during interviews, and (4)
      aged 18 and over. RESULTS: The findings showed that three interrelated factors
      promoted self-care independence among residents in long-term care facilities.
      They included: (1) family members' attitudes/behaviors and concerns, (2)
      residents' characteristics and attitudes, and (3) staff's attitudes/behaviors.
      Hence, to promote elders' self-care independence, family caregivers indicated
      that staff, family caregivers and elders should work together. This included:
      setting goals, building trustful relationships between staff and family
      caregivers, and routinely reporting the elder's condition to families.
      CONCLUSION: This study provided important information that, elders, family
      members, and staff caregivers of long-term care facilities should build a
      partnership and set a mutual goal, to improve self-care performance among
      residents in long-term care facilities.

PMID- 23164720
TI  - Engineering three-dimensional cell mechanical microenvironment with hydrogels.
AB  - Cell mechanical microenvironment (CMM) significantly affects cell behaviors such
      as spreading, migration, proliferation and differentiation. However, most studies
      on cell response to mechanical stimulation are based on two-dimensional (2D)
      planar substrates, which cannot mimic native three-dimensional (3D) CMM.
      Accumulating evidence has shown that there is a significant difference in cell
      behavior in 2D and 3D microenvironments. Among the materials used for engineering
      3D CMM, hydrogels have gained increasing attention due to their tunable
      properties (e.g. chemical and mechanical properties). In this paper, we provide
      an overview of recent advances in engineering hydrogel-based 3D CMM. Effects of
      mechanical cues (e.g. hydrogel stiffness and externally induced stress/strain in
      hydrogels) on cell behaviors are described. A variety of approaches to load
      mechanical stimuli in 3D hydrogel-based constructs are also discussed.

PMID- 23164721
TI  - A pooled analysis of the effect of endovascular cooling on infarct size in
      patients with ST-elevation myocardial infarction.
AB  - AIMS: Prior evaluations of endovascular cooling during primary percutaneous
      coronary intervention (PCI) for acute myocardial infarction (AMI) have suggested
      variability in treatment effect related to core temperature at the time of
      reperfusion, to infarct location and time from symptom onset to reperfusion.
      Recent results from a randomised feasibility study suggest rapid induction of
      hypothermia in primary PCI results in a significant reduction in infarct size
      (IS). METHODS AND RESULTS: Outcomes from two randomised trials of hypothermia in
      primary PCI were pooled to examine IS as a percentage of left ventricular
      myocardium assessed by SPECT or magnetic resonance imaging. Compared with
      controls (n=103), hypothermia (n=94) was associated with a significant 24%
      relative reduction (RR) in IS (10.7+/-1.3% vs. 14.1+/-1.6%, mean+/-SEM, p=0.049).
      Among hypothermia-treated patients for whom core temperature <35C degrees  was
      achieved before reperfusion, IS was reduced by 37% (8.8+/-1.7% vs. 14.1+/-1.6%,
      p=0.01), a benefit observed for both anterior (14.9+/-2.9% vs. 22.2+/-2.7%, RR
      33%; p=0.03) and inferior infarcts (4.5+/-1.4% vs. 7.7+/-1.3%, RR 42%; p=0.04).
      CONCLUSIONS: In a pooled analysis of randomised trials evaluating adjunctive
      hypothermia in primary PCI, achievement of core body temperature <35 degrees C
      before reperfusion may reduce infarct size with a similar efficacy for both
      anterior and inferior MI.

PMID- 23164722
TI  - Outcomes of the modified Brostrom procedure using suture anchors for chronic
      lateral ankle instability--a prospective, randomized comparison between single
      and double suture anchors.
AB  - The present prospective, randomized study was conducted to compare the clinical
      outcomes of the modified Brostrom procedure using single and double suture
      anchors for chronic lateral ankle instability. A total of 50 patients were
      followed up for more than 2 years after undergoing the modified Brostrom
      procedure. Of the 50 procedures, 25 each were performed using single and double
      suture anchors by 1 surgeon. The Karlsson scale had improved significantly to
      89.8 points and 90.6 points in the single and double anchor groups, respectively.
      Using the Sefton grading system, 23 cases (92%) in the single anchor group and 22
      (88%) in the double anchor group achieved satisfactory results. The talar tilt
      angle and anterior talar translation on stress radiographs using the Telos device
      had improved significantly to an average of 5.7 degrees  and 4.6 mm in the single
      anchor group and 4.5 degrees  and 4.3 mm in the double anchor group,
      respectively. The double anchor technique was superior with respect to the
      postoperative talar tilt. The single and double suture anchor techniques produced
      similar clinical and functional outcomes, with the exception of talar tilt as a
      reference of mechanical stability. The modified Brostrom procedure using both
      single and double suture anchors appears to be an effective treatment method for
      chronic lateral ankle instability.

PMID- 23164723
TI  - [Thrombosis of the superior vena cava revealing a protein S deficiency].
AB  - Thrombosis of the superior vena cava is attached to several causes including
      deficiency of the protein S. It occurs gradually by a superior vena cava
      syndrome. We report a patient aged 22 years, no toxic habits or bipolar
      aphthosis, which presented for 3 months a superior vena cava syndrome. The
      radiological and biological assessments confirmed thrombosis of the superior vena
      cava and a deficit of the protein S for which the patient was put under
      anticoagulant therapy with good clinical and radiological improvement. Through
      this observation, the authors report a rare cause of thrombosis of the superior
      vena cava which is the isolated protein S deficiency and provide a review of the
      literature.

PMID- 23164724
TI  - New insights from China on the efficacy of ECT in schizophrenia.

PMID- 23164725
TI  - Rumpel Leede phenomenon.

PMID- 23164726
TI  - One anesthesia mump: another possible mechanism.

PMID- 23164727
TI  - Within-subject comparison of propofol and methohexital anesthesia.

PMID- 23164729
TI  - Noninvasive determination of arterial elasticity and blood pressure. Part II: 
      elastogram and blood pressure determination.
AB  - OBJECTIVE: The oscillometric method is used in the medical practice for
      measurement of arterial blood pressure and, rarely, for estimation of arterial
      elasticity. In the previous paper of this series, the relations between arterial
      volume pulsations and volume-to-pressure curve (elastogram) were examined
      resolving the problem for evaluation of arterial volume pulsations from known
      elastogram and systolic (ps)/diastolic (pd) blood pressure. Some features were
      found that are considered to be elastogram attributes. The aim of the present
      work is to resolve the inverse problem - graphical reconstruction of the
      elastogram from oscillometric data and determination of blood pressure.
      PARTICIPANTS AND METHODS: The elastograms of an idealized arterial model as well
      as of experimental oscillometric records (five men, five women) are processed
      graphically. RESULTS: The method for reconstruction is developed with the
      idealized volume pulsations of the arterial model, establishing full
      correspondence of the elastogram fixed in the model with those determined here.
      The accuracy of this reconstruction is assessed: a pulse pressure variability of
      12% leads to an ~2-9% error of the reconstructed elastogram. Thereafter,
      experimental elastograms are reconstructed graphically, and the correct pulse
      pressure and blood pressure are determined. The experimentally determined blood
      pressure is statistically compared with that simultaneously auscultatory
      measured. Satisfactory correspondence between values of ps/pd is found. A method
      of objective comparison between elastograms after normalization is suggested.
      CONCLUSION: A novel graphical, nonempirical method for a noninvasive
      reconstruction of the elastogram and determination of blood pressure is
      presented. The method can be applied easily in automated blood pressure
      measurement devices.

PMID- 23164730
TI  - Is 'object-centred neglect' a homogeneous entity?
AB  - The nature of object-centred (allocentric) neglect and the possibility of
      dissociating it from egocentric (subject-centred) forms of neglect are
      controversial. Originally, allocentric neglect was described by Gainotti, D'Erme,
      Monteleone & Silveri (1986) and Gainotti, Messerli, & Tissot (1972) in patients
      who reproduced all the elements of a multi-object scene, but left unfinished the
      left side of one or more of them. More recently, however, Karnath, Mandler, and
      Clavagnier (2011) have claimed that the severity of allocentric neglect worsens
      when a complex 'object' shifts from an ipsilesional to a contralesional
      egocentric position. On the basis of these and of other clinical data, showing
      that allocentric and egocentric neglect are strongly associated, they have
      questioned the possibility of dissociating these two forms of neglect, suggesting
      that egocentric and allocentric neglect constitute different manifestations of
      the same disturbed system. Since these statements were inconsistent with the
      clinical findings which had prompted the construct of object-centred neglect, we
      checked in a group of right brain-damaged patients, who had copied the original
      multi-object scene, if the degree of neglect for the left side of figures varied
      as a function of their position on the horizontal axis. Furthermore, we reviewed
      all papers where copies of other multi-object scenes had been reported. Results
      of both studies failed to confirm the assumption of a relationship between
      spatial location of the stimulus and severity of object-centred neglect. This
      discrepancy between our data and those obtained by Karnath et al. (2011) could be
      due to the characteristics of stimuli and of procedures used to evaluate 'object
      centred' neglect. If the stimulus is complex and the task requires its thorough
      exploration, the spatial location of the stimulus will influence the severity of
      'object-centred neglect'. If, on the contrary, the stimulus is simple and can be
      identified with few eye fixations, the spatial location of the stimulus should
      not influence the severity of 'object-centred neglect'. In any case, our data
      confirm the possibility of dissociating allocentric from egocentric neglect.

PMID- 23164731
TI  - Personal and impersonal stimuli differentially engage brain networks during moral
      reasoning.
AB  - Moral decision making has recently attracted considerable attention as a core
      feature of all human endeavors. Previous functional magnetic resonance imaging
      studies about moral judgment have identified brain areas associated with
      cognitive or emotional engagement. Here, we applied graph theory-based network
      analysis of event-related potentials during moral decision making to reveal the
      personal/impersonal distinction in the organization of functional connectivity.
      Our results indicated that the personal task had more larger long-range
      connections involved in frontal regions and the right hemisphere, and higher
      network efficiency of some frontal electrodes such as F2 than the impersonal.
      These might be related to brain resource reorganization contributing to efficient
      conflict resolution. These findings provide new insights into neural mechanisms
      of moral dilemmas.

PMID- 23164733
TI  - Targeting membrane trafficking in infection prophylaxis: dynamin inhibitors.
AB  - Many pathogens hijack existing endocytic trafficking pathways to exert toxic
      effects in cells. Dynamin controls various steps of the intoxication process used
      by numerous pathogenic bacteria, viruses, and toxins. Targeting dynamin with
      pharmaceutical compounds may therefore have prophylactic potential. Here we
      review the growing number of pathogens requiring dynamin-dependent trafficking to
      intoxicate cells, outline the mode of internalization that leads to their
      pathogenicity, and highlight the protective effect of pharmacological and genetic
      approaches targeting dynamin function. We also assess the methodologies used to
      investigate the role of dynamin in the intoxication process and discuss the
      validity and potential pitfalls of using dynamin inhibitors (DIs) as
      therapeutics.

PMID- 23164732
TI  - A model of amygdala-hippocampal-prefrontal interaction in fear conditioning and
      extinction in animals.
AB  - Empirical research has shown that the amygdala, hippocampus, and ventromedial
      prefrontal cortex (vmPFC) are involved in fear conditioning. However, the
      functional contribution of each brain area and the nature of their interactions
      are not clearly understood. Here, we extend existing neural network models of the
      functional roles of the hippocampus in classical conditioning to include
      interactions with the amygdala and prefrontal cortex. We apply the model to fear
      conditioning, in which animals learn physiological (e.g. heart rate) and
      behavioral (e.g. freezing) responses to stimuli that have been paired with a
      highly aversive event (e.g. electrical shock). The key feature of our model is
      that learning of these conditioned responses in the central nucleus of the
      amygdala is modulated by two separate processes, one from basolateral amygdala
      and signaling a positive prediction error, and one from the vmPFC, via the
      intercalated cells of the amygdala, and signaling a negative prediction error. In
      addition, we propose that hippocampal input to both vmPFC and basolateral
      amygdala is essential for contextual modulation of fear acquisition and
      extinction. The model is sufficient to account for a body of data from various
      animal fear conditioning paradigms, including acquisition, extinction,
      reacquisition, and context specificity effects. Consistent with studies on
      lesioned animals, our model shows that damage to the vmPFC impairs extinction,
      while damage to the hippocampus impairs extinction in a different context (e.g.,
      a different conditioning chamber from that used in initial training in animal
      experiments). We also discuss model limitations and predictions, including the
      effects of number of training trials on fear conditioning.

PMID- 23164735
TI  - Resolution of nebivolol-induced coronary vasospasm by intracoronary nitroglycerin
      during a coronary angiogram.
AB  - Nebivolol is a novel beta1-selective beta-blocker with vasodilator properties
      mediated through activation of the l-arginine-nitric oxide pathway. There is no
      published report of coronary artery spasm associated with nebivolol. We describe
      a 64-year-old female patient who developed unstable angina secondary to nebivolol
      induced vasospastic angina which was also visible during coronary angiography.

PMID- 23164737
TI  - First experience of 3D rotational angiography fusion with NavX electroanatomical
      mapping to guide catheter ablation of atrial fibrillation.
AB  - BACKGROUND: Rotational angiography of the left atrium with 3-dimensional
      reconstruction (3DATG) is a new imaging tool to guide atrial fibrillation (AF)
      ablation. Its role as part of a complex imaging strategy with NavX has not yet
      been evaluated. OBJECTIVE: To determine the feasibility of using 3DATG fusion
      with NavX in guiding AF ablation. METHODS: 3DATG was performed in 24 consecutive
      patients undergoing AF ablation by using the Philips Allura Xper FD 10 system.
      The 3DATG anatomical shell was fused with NavX data (fusion group). Procedural
      characteristics of the fusion group were compared to 12 patients (control group)
      who underwent AF ablation guided by NavX only during the preceding 6 months.
      RESULTS: 3DATG/NavX fusion was successful in all patients and required 12 +/- 2
      fiducial points. Total radiation dose, fluoroscopy, and procedural times were
      significantly lower in the fusion group despite additional time and radiation
      exposure from 3DATG (total radiation dose of 20.4 mSv in the fusion group vs 34.0
      mSv in the control group; P = .04; fluoroscopy time 50.5 minutes vs 69.7 minutes;
      procedural time 4.3 hours vs 5.1 hours). Ablation was successful acutely in 35 of
      36 patients. At follow-up, 14 of 24 (58.3%) patients in the fusion group and 6 of
      12 (50%) patients in the control group were in sinus rhythm. There was 1
      complication in each group. CONCLUSIONS: AF ablation guided by 3DATG/NavX fusion
      is associated with reduced procedural time and radiation exposure and similar
      clinical outcomes when compared with NavX mapping only. 3DATG/NavX fusion may
      provide a lower radiation alternative to NavX only or preprocedural cardiac
      computed tomography as part of complex imaging strategies.

PMID- 23164738
TI  - [Inhibiting contractility without necrosis: would it be helpful for hypertrophic
      cardiomyopathy? Experimental model of intramyocardial botulinum toxin and
      wortmannin].
AB  - The purpose of this paper is to introduce a new idea: local inhibition of
      contractility without necrosis. It's potential usefulness in hypertrophic
      cardiomyopathy treatment is discussed and 2 pharmacological models,
      administrating botulinum toxin and wortmannin directly in the myocardium are
      disclosed.

PMID- 23164739
TI  - [Postoperative evolution of pulmonary arterial hypertension associated with
      patent ductus arteriosus at an altitude of 2680 meters above sea level].
AB  - INTRODUCTION: Patent ductus arteriosus in Toluca can cause pulmonary hypertension
      and ranks first surgery of congenital heart disease in Toluca, Mexico. METHODS:
      In the period between January 2006 and December 51 patients with patent ductus
      arteriosus went to surgery: 34 (66.7%) were female. We study the reversibility of
      pulmonary arterial pressure and the left cavities dilatation after surgical
      closure of the ductus arteriosus and postoperative complications are described in
      a population of Toluca, located at an altitude of 2680 meters over the sea.
      RESULTS: The reversibility of pulmonary pressure ocurred in 88% of cases. We also
      observed a decrease in the diameters of the left chambers manifested by a ratio
      of left atrium/aortic annulus before surgery of 2.0 +/- 0.41 SD and after surgery
      of 1.36 +/- 0.25 SD, (p<0.001). The successful closure of the ductus arteriosus
      was 94.1% immediately and mediate 98.0%. Postoperative complications ocurred in
      13.8%, being the main infection and surgical wound hematoma (5.9%), pneumothorax
      (3.9%), pneumonia (2.0%) and pleural efusion (2.0%). CONCLUSIONS: Pulmonary
      arterial hypertension secundary to patent ductus arteriosus is reversible in the
      mayority of cases after surgical closure, including residents of village above
      2500 meters over the sea.

PMID- 23164740
TI  - [Circumflex angioplasty in a patient with type IV dual left anterior descending
      coronary artery. Proposal for updating the classification of Spindola-Franco].
AB  - The normal anatomy of coronary arteries includes a kind of variants with regard
      to its origin, distribution and route, which makes that 2 patients do not have
      coronary arteries exactly alike. Left anterior descending artery could have
      anatomical variations that do not affect the normal supply of blood to the
      corresponding myocardial territory. In our 25 years of experience, and more than
      11,000 coronary angiographies, we have found only one patient with a type IV dual
      left anterior descending coronary artery. In this article we show the case of a
      patient with the described coronary anomaly, presenting a severe stenosis of the
      circumflex artery which was successfully treated percutaneously. Besides, a
      proposal for updating the classification of Spindola-Franco is made, where the 4
      types previously described were kept invariable, and 7 anatomical variants or
      subtypes were added.

PMID- 23164734
TI  - Postnatal development, maturation and aging in the mouse cochlea and their
      effects on hair cell regeneration.
AB  - The organ of Corti in the mammalian inner ear is comprised of mechanosensory hair
      cells (HCs) and nonsensory supporting cells (SCs), both of which are believed to
      be terminally post-mitotic beyond late embryonic ages. Consequently, regeneration
      of HCs and SCs does not occur naturally in the adult mammalian cochlea, though
      recent evidence suggests that these cells may not be completely or irreversibly
      quiescent at earlier postnatal ages. Furthermore, regenerative processes can be
      induced by genetic and pharmacological manipulations, but, more and more reports
      suggest that regenerative potential declines as the organ of Corti continues to
      age. In numerous mammalian systems, such effects of aging on regenerative
      potential are well established. However, in the cochlea, the problem of
      regeneration has not been traditionally viewed as one of aging. This is an
      important consideration as current models are unable to elicit widespread
      regeneration or full recovery of function at adult ages yet regenerative
      therapies will need to be developed specifically for adult populations. Still,
      the advent of gene targeting and other genetic manipulations has established mice
      as critically important models for the study of cochlear development and HC
      regeneration and suggests that auditory HC regeneration in adult mammals may
      indeed be possible. Thus, this review will focus on the pursuit of regeneration
      in the postnatal and adult mouse cochlea and highlight processes that occur
      during postnatal development, maturation, and aging that could contribute to an
      age-related decline in regenerative potential. Second, we will draw upon the
      wealth of knowledge pertaining to age related senescence in tissues outside of
      the ear to synthesize new insights and potentially guide future research aimed at
      promoting HC regeneration in the adult cochlea.

PMID- 23164741
TI  - [Successful endovascular treatment of nutcracker's syndrome with self-expanding
      stent].
AB  - Nutcracker's syndrome is caused by compression of the left renal vein between
      aorta and superior mesenteric artery, causing extrinsic compression generated
      functional stenosis. This causes congestion and hypertension of the left renal
      vein resulting in insufficiency and left gonadal vein varicose, unilateral
      hematuria and left flank pain, diagnosis is rarely identified by their low
      frequency and difficulty of suspecting, treatment of nutcracker's syndrome
      include renal autotransplantation, transposition of superior mesenteric artery
      revascularization and recently stenting in renal vein, we present the case of a
      patient, who showed this pathology by diagnostic support by image studies, was
      performed successfully implant a self-expanding stent with immediate success
      criteria by angiography, collateral reduction and by disappearance of cava/renal
      gradient.

PMID- 23164742
TI  - [Is salt sensitive hypertension an inflammatory disease? Role of lymphocytes and
      macrophages].
AB  - High blood pressure is a public health problem. This entity affects 43% of the
      mexican population and is considered a major risk factor for development of
      stroke, cardiac failure and chronic kidney disease. Hypertension prevalence has
      increased over the last decades, mainly because of high salt diet. There is
      evidence showing that salt-sensitive hypertension develops structural changes as
      tubular dilation, patchy interstitial fibrosis, osteopontin expression and
      lymphocytic/macrophage tubulointerstitial infiltrate that blunts urinary sodium
      excretion and therefore promotes HBP. It has been shown that this structural
      damage has an inflammatory origin and that immunosuppresant drugs down-regulates
      tissular injury and improves blood pressure control. In summary, this salt
      sentitive hypertension data can be used in development of new and potent blood
      pressure drugs.

PMID- 23164743
TI  - [Double outlet right ventricle. Embryological approach].
AB  - OBJECTIVE: It is proposed a pathogenetic explanation that explains the
      morphogenesis of the anatomic variants of double outlet right ventricle. METHOD:
      An anatomic embryological correlation was made in which the plane separating the
      outlets and great arteries in the types of this cardiopathy was compared with the
      normal truncoconal septum in the embryonic heart. Thirty five hearts with double
      outlet right ventricle were described, fifteen with great arteries slightly
      crossed, ten with side by side great arteries and ten with anterior aorta and
      posterior pulmonary artery. The cephalic border of the truncoconal septum was
      compared with its inferior border in each group. With this procedure we
      calculated the type of torsion of the truncoconal septum. RESULTS: In the
      slightly crossed great arteries the truncoconal twist was of 135 degrees  in side
      by side great arteries the twist was of 90 degrees  and in anterior right aorta
      the truncoconal septum was straight with 0 degrees  of rotation, and with left
      anterior aorta the rotation was of -90 degrees . CONCLUSION: Embryologically
      double outlet right ventricle is originated by the persisting continuity between
      the right ventricle with the truncus and conus which form the great arteries and
      their outlets. The anatomic variations are the consequence of progressive
      detortion of the truncoconal septum followed by a torsion of -90 degrees .

PMID- 23164744
TI  - [The electrophysiology of Wolff-Parkinson-White in the asymptomatic patient with
      activity or with high professional risk].
AB  - OBJECTIVE: Describe the electrophysiological characteristics in subjects with
      asymptomatic Wolff-Parkinson-White with sports activities or high professional
      responsibility. METHODS: Nineteen subjects, mean age 33 +/- 13 years (group A).
      The electrophysiological characteristics were compared with a matched group with
      symptomatic WPW (group B). RESULTS: At baseline the anterograde refractory period
      and the anterograde conduction 1:1 over the accessory pathway were longer in
      group A (300 +/- 48 ms vs 262 +/- 32 ms, p < 0.05 and 355 +/- 108 ms vs 307 +/-
      86 ms, p < 0.05), respectively. None of group A had a anterograde refractory
      period< 250 ms and 58% showed absence of retrograde conduction over the accessory
      pathway vs 4% of group B (p < 0.001). Induction of tachycardia was significantly
      less in group A (5%) than in group B (92%) (p < 0.001). Atrial fibrillation was
      induced in only one of group A vs 32% of group B (p < 0.001). CONCLUSION: We
      confirm the benign electrophysiological characteristics in asymptomatic compared
      to symptomatic subjects. Poor anterograde conduction along with absence of
      retrograde conduction explains the low frequency of tachyarrhythmias and would
      not support the routine investigation of all asymptomatic subjects. But, due to
      possible consequences, remains the systematic indication for preventive ablation
      in the subgroup of asymptomatic subjects with sporting activities or high
      professional responsibility.

PMID- 23164745
TI  - [Characterization of the vascular pulsatile flow through in vitro observations on
      biologic and mechanical models].
AB  - OBJECTIVE: The evidence accumulated on the use of pulsatile and non-pulsatile
      flow-dependent devices raises a controversy concerning the effects of the flow
      type on the Circulatory system. This paper proposes to characterize the
      properties of pulsatile flow in elastic conduits in order to determine how the
      pulse affects the system and to determine the specific details of the flow in the
      vascular bed. METHODS: The biomechanical properties of pulsatile flow were
      measured on flexible (calf venous vessel), and rigid (plastic pipe) conduits in
      which the flow was implemented using a pneumatic elastic sack-like pumping
      device. RESULTS: The experimental data and the biomechanical analysis of the
      pulsing flow was used to determine the flow pattern in order to develop a
      mechanical model explaining the effects of the pulse on the vascular system. The
      resulting model includes the flow's general condition (mechanical component) and
      its effects on the vascular system (biological/physiological component).
      CONCLUSIONS: The model proposed here allows determining the relationship between
      the flow conditions and the reaction on the wall; it also allows unifying the
      interpretation of fluid-dynamic factors affecting these phenomena and represents
      a warning system about the effects of flow changes on the operation of
      circulatory assistance devices.

PMID- 23164746
TI  - Spatial and temporal attention revealed by microsaccades.
AB  - We compared the spatial and temporal allocation of attention as revealed by
      microsaccades. Observers viewed several concurrent "rapid serial visual
      presentation" (RSVP) streams in the periphery while maintaining fixation. They
      continually attended to, and discriminated targets in one particular, cued
      stream. Over and above this continuous allocation, spatial attention transients
      ("attention shifts") were prompted by changes in the cued stream location and
      temporal attention transients ("attentional blinks") by successful target
      discriminations. Note that the RSVP paradigm avoided the preparatory suppression
      of microsaccades in anticipation of stimulus or task events, which had been
      prominent in earlier studies. Both stream changes and target discriminations
      evoked residual modulations of microsaccade rate and direction, which were
      consistent with the presumed attentional dynamics in each case (i.e., attention
      shift and attentional blink, respectively). Interestingly, even microsaccades
      associated with neither stream change nor target discrimination reflected the
      continuous allocation of attention, inasmuch as their direction was aligned with
      the meridian of the target stream. We conclude that attentional allocation shapes
      microsaccadic activity continuously, not merely during dynamic episodes such as
      attentional shifts or blinks.

PMID- 23164747
TI  - Vibrio cholerae non-O1 and non-O139 bacteremia in a non-traveler Portuguese
      cirrhotic patient: first case report.
AB  - Bacteremia due to Vibrio cholerae non-O1 and non-O139 is a rare condition and
      potentially fatal. We report a case of bacteremia due to V. cholerae non-O1 and
      non-O139 in a Portuguese male with Hepatitis C cirrhosis, admitted due to acute
      diarrhea, after consuming shrimp. He had no recent travels. To our knowledge,
      this is the first reported case of bacteremia due to V. cholerae non-O1 and non
      O139 in Portugal.

PMID- 23164748
TI  - Comparison of intravenous adenosine and intravenous regadenoson for the
      measurement of pressure-derived coronary fractional flow reserve.
AB  - AIMS: Defining the clinical and physiologic significance of an intermediate
      coronary artery stenosis is aided by measurement of fractional flow reserve
      (FFR). Adenosine is the most common agent used in the cardiac catheterisation
      laboratory for the measurement of FFR. Regadenoson, a selective adenosine
      receptor agonist, with fewer side effects than adenosine has been used
      extensively in stress testing to induce hyperaemia. We postulated that FFR
      measurements would be equivalent following administration of regadenoson and
      adenosine. METHODS AND RESULTS: Twenty patients with an angiographic intermediate
      coronary artery stenosis (50% to 80%) were included in the study. FFR was
      measured during three minutes of intravenous (IV) adenosine infusion and for five
      minutes after an injection of regadenoson. The mean difference between the FFR
      measured by IV adenosine and IV regadenoson was 0.0040 (min -0.04, max +0.04,
      standard deviation [SD] 0.025). There was a strong linear correlation between the
      FFR measured by IV adenosine and IV regadenoson (R2 linear=0.933). The FFR at
      maximum hyperaemia was achieved earlier using regadenoson than adenosine (59+/
      24.5 sec vs. 93+/-44.5 sec, p=0.01). CONCLUSIONS: Regadenoson produces similar
      pressure-derived FFR compared to IV adenosine infusion.

PMID- 23164749
TI  - Ab initio thermal transport properties of nanostructures from density functional
      perturbation theory.
AB  - We present a comprehensive first-principles study of the thermal transport
      properties of low-dimensional nanostructures such as polymers and nanowires. An
      approach is introduced where the phonon quantum conductance is computed from the
      combination of accurate plane-wave density functional theory electronic structure
      calculations, the evaluation of the interatomic force constants through density
      functional perturbation theory for lattice dynamics, and the calculation of
      transport properties by a real-space Green's function method based on the
      Landauer formalism. This approach is computationally very efficient, can be
      straightforwardly implemented as a post-processing step in a standard electronic
      structure calculation (Quantum ESPRESSO and WanT in the present implementation),
      and allows us to directly link the thermal transport properties of a device to
      the coupling, dimensionality, and atomistic structure of the system. It provides
      invaluable insight into the mechanisms that govern heat flow at the nanoscale and
      paves the way  to the fundamental understanding of phonon engineering in
      nanostructures.

PMID- 23164750
TI  - Zero-quantum filtered pure shift TOCSY.
AB  - The high spectral resolution provided by the pure shift TOCSY experiment can be
      significantly improved by zero-quantum filtering which eliminates dispersive anti
      phase contributions from the spectrum.

PMID- 23164751
TI  - Reversal modes and magnetostatic interactions in Fe3O4/ZrO2/Fe3O4 multilayer
      nanotubes.
AB  - Reversal modes and magnetostatic interactions of multilayered
      Fe(3)O(4)/ZrO(2)/Fe(3)O(4) nanotubes consisting of a ferromagnetic internal tube,
      an intermediate non-magnetic spacer and an external magnetic shell are
      investigated as a function of their geometric parameters and compared with those
      produced inside the pores of anodic alumina membranes by atomic layer deposition.
      Based on a continuum approach we obtained analytical expressions that underline
      the first experimental results and support their interpretation that the system
      of multilayer tubes behaves as the reversal of two isolated systems. It is
      observed that the magnetostatic interaction between both phases depends on the
      magnetic configurations in each phase and also on the geometrical parameters
      considered. These structures have potential applications in novel spintronics
      devices, ultra-small magnetic media and other nano-devices.

PMID- 23164752
TI  - Natriuretic peptides in acute chest pain and acute coronary syndrome:  from
      pathophysiology to clinical and prognostic applications.
AB  - BACKGROUND: Plasma levels of natriuretic peptides (NPs) appear to have an
      important prognostic value in many clinical settings including coronary artery
      disease and provide additional information about cardiovascular risk. CONTENT:
      The aim of this study was to review the literature on the role of NPs in the
      prognosis and management of patients with acute chest pain and acute coronary
      syndrome (ACS). Several trials have assessed the prognostic value of NPs as
      biomarkers of myocardial injury for risk stratification in patients with acute
      chest pain and ACS. The additional prognostic information on measurement of NP
      levels is independent of that provided by cardiac troponin and the various
      clinical and ECG features and traditional risk markers available at hospital
      admission. CONCLUSION: Although measurement of the level of NPs is not
      recommended as a diagnostic tool in ACS management, their concentrations seem to
      distinguish patients at a higher risk not only for heart failure but also for
      ACS. NPs are a good risk marker for ACS, in addition to troponins, but have not
      yet been proved suitable for guiding therapy.

PMID- 23164753
TI  - Electrospinning of carboxyethyl chitosan/poly(vinyl alcohol)/silk fibroin
      nanoparticles for wound dressings.
AB  - Composite nanofibrous membranes of water-soluble N-carboxyethyl
      chitosan/poly(vinyl alcohol)/silk fibroin nanoparticles were successfully
      fabricated by electrospinning. The composite nanofibers were subjected to
      detailed analysis by scanning electron microscopy (SEM), X-ray diffraction (XRD)
      and differential scanning calorimetry (DSC). SEM results investigated that the
      morphology and diameter of the nanofibers were affected by silk fibroin
      nanoparticles content. XRD and DSC demonstrated that there was intermolecular
      hydrogen bonding among the molecules of carboxyethyl chitosan, silk fibroin and
      PVA. The crystalline microstructure of the electrospun fibers was not well
      developed. The indirect cytotoxicity assessments of the nanofibers were studied.
      The result showed the nanofibers had good biocompatibility. This novel
      electrospun matrix would be used as potential wound dressing for skin
      regeneration.

PMID- 23164754
TI  - Phenolic antioxidants-functionalized quaternized chitosan: synthesis and
      antioxidant properties.
AB  - In this work, two kinds of phenolic antioxidants-functionalized quaternized
      chitosan were synthesized in order to develop aqueous soluble antioxidant-polymer
      conjugates. Quaternized chitosan conjugated with gallic acid or caffeic acid was
      carried out and the antioxidant properties of the products (namely gallic acid
      quaternized chitosan and caffeic acid-quaternized chitosan) against hydroxyl
      radical, superoxide-radical and DPPH-radical were evaluated in vitro,
      respectively. The scavenging activities of the obtained gallic acid-quaternized
      chitosan and caffeic acid-quaternized chitosan exhibit a remarkable improvement
      over those of either chitosan or quaternized chitosan. And the scavenging effect
      indices of the products were all higher than 90% at a concentration of 1000
      MUg/mL. Because gallic acid-quaternized chitosan and caffeic acid-quaternized
      chitosan are convenient to prepare and possess improved potential activities,
      these materials may represent an attractive new platform for utilizations of
      chitosan.

PMID- 23164755
TI  - Maturation of murine bone marrow dendritic cells induced by acidic Ginseng
      polysaccharides.
AB  - In this study, we report that a acidic polysaccharide (AGP) isolated from a
      Chinese medicinal herb, named Ginseng (Panax giseng C.A. Meyer), induces
      maturation of bone marrow dendritic cells (BMDCs) via concrete changes both
      inside and outside BMDCs. The impacts of AGP on BMDCs were assessed with use of
      conventional scanning electronic microscopy (SEM), transmission electronic
      microscopy (TEM) for morphology, flow cytometry (FCM) for key surface molecules,
      cytochemistry assay, FITC-dextran, bio-assay for phagocytosis and enzyme linked
      immunosorbent assay (ELISA) for production of cytokines. Our results elucidated
      that PPS promoted maturation of BMDCs via changes as reflected by the down
      regulation of acid phosphatase (ACP) activity inside the BMDCs, which occurs when
      phagocytosis of BMDCs to antigen decreased, while antigen presentation increased
      upon maturation, higher expression of key surface molecules of MHC II, CD80,
      CD86, CD83, and CD40, and releasing higher level of cytokines IL-12 and low level
      of TNF-alpha. Our study suggest that AGP play marked immunostimulating role on
      the maturation of murine BMDCs through precise regulation of phagocytosis and
      enzyme activities inside the BMDCs.

PMID- 23164756
TI  - Characterization and antitumor activities of a polysaccharide from the rhizoma of
      Menispermum dauricum.
AB  - The rhizome of Menispermum dauricum DC (Menispermaceae) is one of the most
      commonly used traditional Chinese medicines officially listed in Chinese
      Pharmacopeia. In present study, we purified a water-soluble polysaccharide (WMDP)
      from this plant and investigated its physicochemical properties. WMDP was a
      homogeneous polysaccharide, with an average molecular weight of approximately
      3.5*10(4)Da, as determined by high-performance gel-permeation chromatography
      (HPGPC). Gas chromatography (GC) analysis identified that WMDP was composed of
      Glc, Gal, Xyl, Rha, Ara and Man in the ratio of 2.45:2.13:1.05:1.29:1.63:1.45.
      The interreaction between Gongo Red and WMDP in NaOH solutions resulted in the
      shift of maximum absorption, indicating WMDP had a triple-helix conformation. We
      also investigated the antitumor activities and mechanisms of WMDP in human
      ovarian carcinoma SKOV3 cells. The experimental evidence showed that WMDP
      significantly inhibited cell proliferation and DNA synthesis in SKOV3 cells in a
      concentration-dependent manner, due to a significant increase in the number of
      apoptotic cells. Furthermore, treatment with WMDP caused a rapid loss of
      intracellular glutathione (GSH) content and stimulation of reactive oxygen
      species (ROS). In addition, nuclear factor-kappa B (NF-kappaB) in SKOV3 cells
      received WMDP treatment was inactivated. Taken together, induction of apoptosis
      on SKOV3 cells by WMDP was mainly associated with ROS production, GSH depletion
      and NF-kappaB inactivation.

PMID- 23164757
TI  - Biomechanics of sit-to-stand transition after muscle damage.
AB  - The purpose of the study was to examine the effects of exercise-induced muscle
      damage on the biomechanics of the sit-to-stand transition (STST). Seventeen
      volunteers participated in an intense, eccentric based, muscle damage protocol of
      knee flexors and extensors via an isokinetic dynamometer. Kinematic and kinetic
      data were collected using a 10-camera optoelectronic system and a force plate 24h
      before and 48h after exercise. Statistical analysis showed significant
      differences in kinematic and kinetic parameters after exercise. Forty-eight hours
      after exercise, the strategy did change and the knee joint relative effort level
      increased significantly. Pelvic and hip kinematics, in conjunction with the knee
      extension joint moment, provided an efficient mechanism to support the
      participants' locomotor system during the STST. These results may be of great
      significance in designing supportive devices, as well as composing rehabilitation
      programs for young or elderly individuals, with various musculoskeletal
      pathologies.

PMID- 23164758
TI  - Association of inflammatory bowel disease with familial Mediterranean fever in
      Turkish children.
AB  - BACKGROUND AND AIMS: Inflammatory bowel disease (IBD) and familial Mediterranean
      fever (FMF) share common clinical and biological features. The prevalence of
      other inflammatory diseases, including IBD, is increased in FMF. We investigated
      the presence of IBD accompanying FMF in patients who were being followed up with
      a diagnosis of FMF and the relation of IBD with the MEFV gene mutation. METHODS:
      A total of 78 children with FMF were enrolled in the study. The patients were
      included in the study independent of the presence of complaints. Colonoscopy for
      IBD was performed if any of the following was present: blood mixed with mucus in
      the stool; chronic diarrhea (loose and frequent stools lasting >4 weeks);
      abdominal pain incompatible with FMF (localized in a certain part of the abdomen,
      not occurring during attacks, >3 days); and positive IgA and IgG anti
      Saccharomyces cerevisiae antibodies and perinuclear antineutrophil cytoplasmic
      antibodies. MEFV gene mutations were analyzed in patients diagnosed as having IBD
      and FMF. RESULTS: Of the 78 patients with a diagnosis of FMF, colonoscopy was
      performed and biopsy samples were taken in 20 patients (25.6%) who had abdominal
      pain incompatible with FMF, chronic diarrhea, bloody stools, and/or positive
      perinuclear anti-neutrophil cytoplasmic antibody or anti-Saccharomyces cerevisiae
      antibody. Histopathological examination resulted in a diagnosis of IBD in 12 of
      the 78 patients (15.4%). MEFV gene mutations were present in all 12 patients
      diagnosed as having IBD. We observed M694 V mutations in 5 of 12 patients
      (41.7%), M680I mutations in 3 (25%), K695R mutations in 3 (25%), and E148Q
      mutations in 1 (8.3%). CONCLUSIONS: We found that the number of patients with FMF
      was higher than the number with IBD in the general population. When IBD
      accompanied FMF, the most common mutation was M694 V; however, the high rate
      (25%) of K695R mutation in our patients with FMF and IBD was not observed in
      previous studies.

PMID- 23164760
TI  - Evaluation of a quantitative fetal fibronectin test for spontaneous preterm birth
      in symptomatic women.
AB  - OBJECTIVE: The purpose of this study was to determine whether quantification of
      cervicovaginal fluid fetal fibronectin (fFN) improves diagnostic accuracy of
      spontaneous preterm birth (sPTB) in symptomatic women. STUDY DESIGN: A
      prospective blinded predefined secondary analysis of a larger study of
      cervicovaginal fluid fFN concentration (nanograms per milliliter) in women
      symptomatic of preterm labor (n =300 women; 22-35 weeks' gestation) with a
      Hologic 10Q system (Hologic, Marlborough, MA). Clinicians were blinded to the
      result until after the delivery, but the qualitative Hologic TLI(IQ) fFN result
      was made available. RESULTS: The positive predictive value for sPTB (<34 weeks'
      gestation) increased from 19%, 32%, 61%, and 75% with increasing thresholds (10,
      50, 200, and 500 ng/mL, respectively). Compared with <10 ng/mL fFN, the relative
      risk of delivery was 5.6 (95% confidence interval [CI], 1.05-29.57), 7.9 (95% CI,
      1.38-45.0), 22.8 (95% CI, 3.84-135.5), and 51.3 (95% CI, 12.49-211.2; P < .01).
      CONCLUSION: Quantitative fFN provides thresholds (10 and 200 ng/mL) in addition
      to the qualitative method (50 ng/mL) to discriminate the risk of sPTB in
      symptomatic women.

PMID- 23164759
TI  - Increased procoagulant function of microparticles in pediatric inflammatory bowel
      disease: role in increased thrombin generation.
AB  - OBJECTIVES: Patients with inflammatory bowel disease (IBD) have a higher risk for
      venous thromboembolism compared with non-IBD subjects. The pathogenic mechanisms
      of the thrombotic events are not fully understood. We investigated levels of
      circulating microparticles and their influence on thrombin generation in
      pediatric patients with IBD during active and quiescent disease compared with
      healthy controls. METHODS: Plasma samples were collected from 33 pediatric
      patients with Crohn disease (CD), 20 pediatric patients with ulcerative colitis
      (UC), and 60 healthy controls. Microparticles' procoagulant activity was measured
      by enzyme-linked immunosorbent assay, and the dependency of thrombin generation
      on microparticles-derived tissue factor was determined by means of calibrated
      automated thrombography. RESULTS: The procoagulant function of microparticles was
      significantly increased in patients with active and inactive CD, and active UC
      compared with controls. Endogenous thrombin potential was significantly higher in
      patients with CD and UC compared with controls. A minor influence of
      microparticles on thrombin generation was only observed for patients with active
      UC. CONCLUSIONS: Our study shows increased procoagulant function of
      microparticles in pediatric patients with active and quiescent CD and active UC
      compared with controls, but demonstrates that they are not a major cause for the
      higher thrombin generation in pediatric patients with IBD.

PMID- 23164761
TI  - Antispasmodic effect of shakuyakukanzoto extract on experimental muscle cramps in
      vivo: role of the active constituents of Glycyrrhizae radix.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Shakuyakukanzoto (SKT) composed of Glycyrrhizae
      radix (G. radix) and Paeoniae radix (P. radix) has been traditionally used in
      Japan, Korea and China as an antispasmodic drug for the treatment of skeletal
      muscle cramps and intestinal cramps. AIM OF THIS STUDY: To evaluate the
      antispasmodic activity of SKT and its two components, as well as to identify the
      key constituents of the components which mediate this effect in skeletal muscles
      in vivo. MATERIALS AND METHODS: An experimental cramp model was constructed to
      evaluate the effects of peripherally-acting muscle relaxants on electrically
      induced cramps under physiological conditions. This was accomplished by
      surgically isolating the motor supply to the gastrocnemius muscle in an
      anesthetized rat and delivering electrical stimuli to an isolated tibial nerve to
      induce tetanic contractions. We first tested dantrolene, a well-known
      peripherally-acting relaxant, to determine the sensitivity and reliability of our
      experimental model. We then evaluated the effects of SKT, P. radix, G. radix, and
      the eight active constituents of G. radix against tetanic contractions. RESULTS:
      We found that dantrolene (10 and 30 mg/kg, i.d.) rapidly and significantly
      inhibited tetanic contractions (P<0.01) irrespective of dose. SKT (0.5, 1.0, and
      2.0 g/kg, i.d.) and G. radix (0.5 and 1.0 g/kg, i.d.) also significantly
      inhibited tetanic contractions (P<0.01) but in a dose-dependent manner owing to
      the actions of six of the eight active constituents in G. radix (liquiritin
      apioside, liquiritigenin, isoliquiritin apioside, isoliquiritigenin,
      glycycoumarin, and glycyrrhetinic acid, 20 MUmol/kg, i.v.). These constituents,
      which include flavonoids, a triterpenoid, and a courmarin derivative,
      demonstrated temporal variations in their inhibitory activity. In contrast, P.
      radix (0.5 and 1.0 g/kg, i.d.) did not show a statistically significant
      antispasmodic effect in our study; however, we previously found that it had a
      significant antinociceptive effect. CONCLUSIONS: Our findings show that SKT
      inhibits tetanic contractions in vivo and that G. radix is the main antispasmodic
      component due to the actions of its active constituents, thus supporting the
      traditional use of SKT. We further propose that SKT containing the antispasmodic
      G. radix and antinociceptive P. radix is a pharmaceutically elegant option for
      muscle cramps as treatment requires a two-pronged approach, i.e., inhibition of
      hyperexcitable skeletal tissues and modulation of the pain accompanying cramps.

PMID- 23164762
TI  - The possible mechanisms of Picrasma quassiodes (D. Don) Benn. in the treatment of
      colitis induced by 2,4,6-trinitrobenzene sulfonic acid in mice.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Picrasma quassiodes (D. Don) Benn.(PQB) is used
      in folk medicines for the treatment of colds, upper respiratory infection, acute
      tonsillitis, acute gastroenteritis, bacillary dysentery and a variety of acute
      infectious diseases in Asia. Although recent reports indicate that PQB has
      antibacterial, and anti-inflammatory effects, its effects on colitis and its
      inhibitory mechanisms have not been previously reported. AIM OF THE STUDY: To
      assess the effects and the mode of action of the extract of Picrasma quassiodes
      (D. Don) Benn.(PQB) on a model of colitis in mice induced by trinitrobenzene
      sulfonic acid (TNBS). MATERIALS AND METHODS: We induced mice colitis using
      TNBS/ethanol, then different doses of Picrasma quassiodes (D. Don) Benn.(PQB)
      extract (100, 200 and 400 mg/kg/day) and sulfasalazine (500 mg/kg/day) were
      administered by gavage for 7 days after the induction of colitis. The mice body
      weight, colonic wet weight, colonic lengths, myeloperoxidase (MPO) activity,
      macroscopic and histological colon injury were observed. Pro-inflammatory
      cytokines such as: tumor necrosis factor-alpha (TNF-alpha) and interleukin-8 (IL
      8) were assayed by enzyme-linked immunoassay. The protein expression of
      cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) in the colons
      were determined by immunohistochemical analysis. RESULTS: PQB administration
      effectively prevented mice diarrhea, decreasing of the body weights, shortening
      of colon length and increasing of colon wet weight. Macroscopic and histological
      examinations also indicated that it was protected against colonic edema,
      ulceration and MPO activity elevation. Furthermore, PQB inhibited the abnormal
      secretions of pro-inflammatory cytokines, such as TNF-alpha and IL-8.
      Additionally, administration of PQB effectively inhibited COX-2 and iNOS protein
      expression. CONCLUSIONS: These results suggest that PQB has an anti-inflammatory
      effect on TNBS-induced colitis due to the down-regulations of the productions and
      expressions of inflammatory mediators, and that it may be a potential
      inflammatory bowel disease (IBD) drug candidate.

PMID- 23164763
TI  - Hexane extract from Polygonum multiflorum attenuates glutamate-induced apoptosis
      in primary cultured cortical neurons.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Polygonum multiflorum has traditionally had wide
      use as an anti-aging treatment in East Asian countries. We investigated the
      neuroprotective effects of Polygonum multiflorum against glutamate-induced
      neurotoxicity with a focus on the anti-apoptotic mechanism in primary cultured
      cortical neurons. MATERIAL AND METHODS: Cell viability, cytotoxicity,
      morphological, flow cytometry, Western blot, and caspase activity assays were
      performed for examination of the neuroprotective effects of active hexane extract
      from Polygonum multiflorum (HEPM). RESULTS: Pretreatment with HEPM resulted in
      significantly decreased glutamate-induced neurotoxicity in a concentration
      dependent manner and also resulted in drastically inhibited glutamate-induced
      apoptosis. Treatment with HEPM resulted in decreased expression of glutamate
      induced death receptor (DR)4, and enhanced expression of glutamate-attenuated
      anti-apoptotic proteins, including Bcl-2, XIAP, and cIAP-1, and slightly reduced
      glutamate-induced cleavage of Bid. In addition, treatment with HEPM resulted in
      suppressed glutamate-induced activation of caspase-8, caspase-9, and caspase-3,
      and, subsequently, decreased degradation of poly(ADP-ribose) polymerase, beta
      catenin, and phospholipase Cgamma1 protein, which are downstream targets of
      activated caspase-3. CONCLUSIONS: The results of this study demonstrated that
      HEPM exerts a neuroprotective effect against glutamate-induced neurotoxicity via
      inhibition of apoptosis. This protection may be mediated through suppression of
      DR4 and up-regulation of Bcl-2, XIAP, and cIAP-1, as well as inhibition of
      caspase activation, resulting in prevention of apoptosis of cortical neurons.

PMID- 23164764
TI  - Hydrogen peroxide-mediated oxidative stress and collagen synthesis in cardiac
      fibroblasts: blockade by tanshinone IIA.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: We have recently reported that tanshinone IIA
      attenuated cardiac fibrosis in two-kidney, two-clip renovascular hypertensive
      rats via inhibiting NAD(P)H oxidase. However, little is known about the cellular
      and molecular mechanisms of tanshinone IIA mediated anti-fibrotic effects in
      cardiac fibroblasts after H(2)O(2) stimulation. The present study was performed
      to investigate whether H(2)O(2) may increase collagen synthesis in cardiac
      fibroblasts by affecting the expression and activity of NAD(P)H oxidase and
      whether the effects of H(2)O(2) on cardiac fibroblasts can be blocked by
      treatment of tanshinone IIA. MATERIALS AND METHODS: Cardiac fibroblasts were
      treated with H(2)O(2) (100 MUmol/L) in the presence or absence of tanshinone IIA
      (1 MUmol/L), NAD(P)H oxidase inhibitors diphenyleneiodonium (10 MUmol/L), siRNA
      p47phox, siRNA-Nox2 and siRNA-Nox4. Collagen synthesis was measured by
      [(3)H]proline incorporation, O(2)(-) production were determined by flow cytometry
      and DHE fluorescence microscopy. NAD(P)H oxidase activity was measured by
      lucigenin-enhanced chemiluminescence. RESULTS: H(2)O(2) induced the activity of
      NAD(P)H oxidase, O(2)(-) production, collagen synthesis and fibronectin
      expression in cardiac fibroblasts, and DPI abolished this induction. Exposure of
      adult rat cardiac fibroblasts to H(2)O(2) had time-dependent increase in the
      expression of p47phox, Nox2 and Nox4 oxidases. In addition, tanshinone IIA
      significantly inhibited H(2)O(2)-induced collagen synthesis via attenuation of
      O(2)(-) generation and NAD(P)H oxidase activity. Moreover, siRNA-mediated
      knockdown of p47phox, Nox2 and Nox4 inhibited H(2)O(2)-induced NADPH oxidase
      activity. H(2)O(2)-induced collagen synthesis and fibronectin expression were
      also inhibited by p47phox, Nox2 and Nox4 knock down. CONCLUSIONS: Our data show
      that NAD(P)H oxidase plays a significant role in regulating collagen synthesis in
      H(2)O(2)-stimulated cardiac fibroblasts. Inhibition of NAD(P)H oxidase with
      tanshinone IIA completely blocked the H(2)O(2)-stimulated collagen production,
      which will raise the experimental basis for using tanshinone IIA to cardiac
      fibrosis in clinic.

PMID- 23164765
TI  - Macrophage activating activity of pyrrole alkaloids from Morus alba fruits.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: The fruits of Morus alba have been traditionally
      used as a tonic to enhance immune responses. MATERIALS AND METHODS: The
      macrophage activating constituents of Morus alba fruits were purified using
      various column chromatography techniques. The structures of isolated compounds
      were determined on the basis of spectroscopic data interpretation such as 1D and
      2D NMR analysis. The macrophage activating activities of isolated compounds were
      evaluated by measuring the production of nitric oxide, TNF-alpha and IL-12 in RAW
      264.7 cells. The phagocytic activity was also evaluated. RESULTS: Five pyrrole
      alkaloids, 5-(hydroxymethyl)-1H-pyrrole-2-carboxaldehyde (1), 2-formyl-1H-pyrrole
      1-butanoic acid (2), 2-formyl-5-(hydroxymethyl)-1H-pyrrole-1-butanoic acid (3), 2
      formyl-5-(methoxymethyl)-1H-pyrrole-1-butanoic acid (4) and Morrole A (5) were
      isolated from the fruits of Morus alba. Morrole A (5) is first reported in nature
      and other pyrrole alkaloids (1-4) are first reported from Morus species. Among
      the isolated compounds, compounds 3 and 4 significantly activated macrophage
      activity by the enhancement of nitric oxide, TNF-alpha and IL-12 production, and
      the stimulation of phagocytic activity in RAW 264.7 cells. CONCLUSION: Pyrrole
      alkaloids, including a new compound, were isolated from Morus alba fruits. These
      compounds activated macrophage activity in RAW 264.7 cells.

PMID- 23164766
TI  - Pulmonary embolism in mechanically ventilated patients requiring computed
      tomography: Prevalence, risk factors, and outcome.
AB  - OBJECTIVE: To estimate the rate of pulmonary embolism among mechanically
      ventilated patients and its association with deep venous thrombosis. DESIGN:
      Prospective cohort study. SETTING: Medical intensive care unit of a university
      affiliated teaching hospital. PATIENTS:  INCLUSION CRITERIA: mechanically
      ventilated patients requiring a thoracic contrast-enhanced computed tomography
      scan for any medical reason. EXCLUSION CRITERIA: a diagnosis of pulmonary
      embolism before intensive care unit admission, an allergy to contrast agents, and
      age younger than 18 yrs. INTERVENTIONS: All the mechanically ventilated patients
      requiring a thoracic computed tomography underwent the standard imaging protocol
      for pulmonary embolism detection. Therapeutic anticoagulation was given
      immediately after pulmonary embolism diagnosis. All the included patients
      underwent a compression ultrasound of the four limbs within 48 hrs after the
      computed tomography scan to detect deep venous thrombosis. RESULTS: Of 176
      included patients, 33 (18.7%) had pulmonary embolism diagnosed by computed
      tomography, including 20 (61%) with no clinical suspicion of pulmonary embolism.
      By multiple logistic regression, independent risk factors for pulmonary embolism
      were male gender, high body mass index, history of cancer, past medical history
      of deep venous thrombosis, coma, and high platelet count. Previous prophylactic
      anticoagulant use was not a risk factor for pulmonary embolism. Of the 176
      patients, 35 (19.9%) had deep venous thrombosis by compression ultrasonography,
      including 20 (57.1%) in the lower limbs and 24 (68.6%) related to central venous
      catheters. Of the 33 pulmonary embolisms, 11 (33.3%) were associated with deep
      venous thrombosis. The pulmonary embolism risk was increased by lower-limb deep
      venous thrombosis (odds ratio 4.0; 95% confidence interval 1.6-10) but not upper
      limb deep venous thrombosis (odds ratio 0.6; 95% confidence interval 0.1-2.9).
      Crude comparison of patients with and without pulmonary embolism shows no
      difference in length of stay or mortality. CONCLUSIONS: In mechanically
      ventilated patients who needed a computed tomography, pulmonary embolism was more
      common than expected. Patients diagnosed with pulmonary embolism were all treated
      with therapeutic anticoagulation, and their intensive care unit or hospital
      mortality was not impacted by the pulmonary embolism occurrence. These results
      invite further research into early screening and therapeutic anticoagulation of
      pulmonary embolism in critically ill patients.

PMID- 23164767
TI  - Guidelines for the use of an insulin infusion for the management of hyperglycemia
      in critically ill patients.
AB  - OBJECTIVE: To evaluate the literature and identify important aspects of insulin
      therapy that facilitate safe and effective infusion therapy for a defined
      glycemic end point. METHODS: Where available, the literature was evaluated using
      Grades of Recommendation, Assessment, Development, and Evaluation (GRADE)
      methodology to assess the impact of insulin infusions on outcome for general
      intensive care unit patients and those in specific subsets of neurologic injury,
      traumatic injury, and cardiovascular surgery. Elements that contribute to safe
      and effective insulin infusion therapy were determined through literature review
      and expert opinion. The majority of the literature supporting the use of insulin
      infusion therapy for critically ill patients lacks adequate strength to support
      more than weak recommendations, termed suggestions, such that the difference
      between desirable and undesirable effect of a given intervention is not always
      clear. RECOMMENDATIONS: The article is focused on a suggested glycemic control
      end point such that a blood glucose >= 150 mg/dL triggers interventions to
      maintain blood glucose below that level and absolutely <180 mg/dL. There is a
      slight reduction in mortality with this treatment end point for general intensive
      care unit patients and reductions in morbidity for perioperative patients,
      postoperative cardiac surgery patients, post-traumatic injury patients, and
      neurologic injury patients. We suggest that the insulin regimen and monitoring
      system be designed to avoid and detect hypoglycemia (blood glucose <= 70 mg/dL)
      and to minimize glycemic variability.Important processes of care for insulin
      therapy include use of a reliable insulin infusion protocol, frequent blood
      glucose monitoring, and avoidance of finger-stick glucose testing through the use
      of arterial or venous glucose samples. The essential components of an insulin
      infusion system include use of a validated insulin titration program,
      availability of appropriate staffing resources, accurate monitoring technology,
      and standardized approaches to infusion preparation, provision of consistent
      carbohydrate calories and nutritional support, and dextrose replacement for
      hypoglycemia prevention and treatment. Quality improvement of glycemic management
      programs should include analysis of hypoglycemia rates, run charts of glucose
      values <150 and 180 mg/dL. The literature is inadequate to support
      recommendations regarding glycemic control in pediatric patients. CONCLUSIONS:
      While the benefits of tight glycemic control have not been definitive, there are
      patients who will receive insulin infusion therapy, and the suggestions in this
      article provide the structure for safe and effective use of this therapy.

PMID- 23164768
TI  - What can we learn from international ventilator-associated pneumonia rates?.

PMID- 23164769
TI  - Critical care in the age of the duty hour regulations: circadian-based
      scheduling, standardized handoffs, and the flipped classroom?.

PMID- 23164770
TI  - Postresuscitation treatment targets-time to emphasize normoxia?

PMID- 23164771
TI  - Transfusion triggers: getting it right!

PMID- 23164772
TI  - Good old physiology in a modern jacket.

PMID- 23164773
TI  - Diagnosis of ventilator-associated pneumonia: do we need surrogate parameters?

PMID- 23164774
TI  - Can we predict cytomegalovirus reactivation in critically ill patients?

PMID- 23164775
TI  - Low 25-hydroxyvitamin D: a significant risk factor for acute kidney injury in
      critically ill patients.

PMID- 23164776
TI  - Tight glycemic control: the baby and the bath water.

PMID- 23164777
TI  - Don't confuse us with the evidence-are we doing the best we can?

PMID- 23164778
TI  - Is it not self-evident that all venous saturations are not created equal?

PMID- 23164779
TI  - Pulmonary embolism in mechanically ventilated patients: what the eye doesn't see,
      the heart can still grieve over.

PMID- 23164780
TI  - Should our crystal ball after cardiac arrest include one of the building blocks
      of life?

PMID- 23164781
TI  - G protein-coupled estrogen receptor: a new therapeutic target in stroke and
      traumatic brain/spinal cord injury?

PMID- 23164782
TI  - Acute respiratory distress syndrome in children: Fortunately uncommon!

PMID- 23164783
TI  - Managing stress in critical illness: a question of balance.

PMID- 23164784
TI  - Percutaneous tracheostomy program: other options exist.

PMID- 23164786
TI  - Trying to win the war against antibiotics resistance.

PMID- 23164788
TI  - Adherence to evidence-based clinical management guidelines: more bang for the
      buck.

PMID- 23164789
TI  - Transcranial echography: an interesting tool for aeromedical evacuations.

PMID- 23164791
TI  - What is the gold standard method for midline structures shift assessment using
      computed tomography?

PMID- 23164793
TI  - Low angiopoietin-1 as a predisposing factor for cerebral vasospasm in cerebral
      malaria.

PMID- 23164795
TI  - [Surgical tetanus in Abidjan, Cote d'Ivoire].
AB  - OBJECTIVE: To describe the epidemiological and clinical features and the outcome
      of tetanus with a surgical wound (open fracture, burn, incision, curettage, etc)
      as the portal of entry. METHODS: Cross-sectional analysis of records of patients
      hospitalized in the department of infectious and tropical diseases in Abidjan for
      surgical tetanus from 2003 to 2008. RESULTS: During the 6-year study period, 29
      cases were identified. They accounted for 11% of all tetanus cases admitted to
      the hospital: 8% from 2003 through 2006 and 14% in 2007 and 2008. The patients'
      average age was 36 years (range: 11-72). Most cases (86%) involved recent
      surgery, in both public (51%) and private (49%) health facilities. All patients
      had generalized tetanus at admission, and 24 (86%) paroxysms. Moderate forms
      predominated (69%). The lethality of tetanus in these surgical wound cases was
      45%. The characteristics statistically associated with death were: age >44 years,
      time of hospitalization >4 days, the presence of paroxysms, and a Dakar prognosis
      score >=4. CONCLUSION: The severity of surgical tetanus remains a concern for
      practitioners. Its high prevalence in recent years demonstrates the need to
      increase surgeons' awareness of tetanus prevention.

PMID- 23164796
TI  - [Cardiovascular risk of immigrants living in Spain according to origin and years
      of stay].
AB  - OBJECTIVE: To assess whether there are differences in the immigrant population in
      terms of the years since their arrival in Spain and their geographical area of
      origin. DESIGN: A cross-sectional study was conducted in three immigrant groups.
      PARTICIPANTS: The groups selected were: a group of Latin American immigrants
      (298), a group of North African immigrants (130) and a group from Eastern Europe
      (114). A control group of 100 from a Spanish population of similar age and sex
      was also included. METHODS: Anthropometric variables were measured, including
      biochemical inflammatory markers, blood pressure and cardiovascular risk
      estimation according to the tables of the European Societies of Hypertension and
      Cardiology. RESULTS: The cardiovascular risk of the three groups of immigrants is
      similar between them (added cardiovascular risk high or very high at 5.5% in
      Latin Americans, 4.3% in North Africans, and 1.6% in immigrants from eastern
      countries), but significantly lower than the Spanish control group (28%). After 8
      years in Spain, cardiovascular risk increases in the three groups of immigrants,
      with those from North Africa and eastern countries being comparable to the
      Spanish group (added cardiovascular risk high or very high of 18.5% in North
      Africans, and 20% in group from eastern countries). This cardiovascular risk was
      higher than the other groups, including the Spanish control group (Latin American
      immigrants 48.7% vs 28% in Spanish group). CONCLUSIONS: The cardiovascular risk
      of immigrants increases over the years in Spain, with this increase being higher
      if they come from Latin America. This increase becomes clinically significant
      after the 8 years of stay in Spain.

PMID- 23164797
TI  - Vaccination to prevent varicella.

PMID- 23164798
TI  - Mitochondrial respiration in human viable platelets--methodology and influence of
      gender, age and storage.
AB  - Studying whole cell preparations with intact mitochondria and respiratory
      complexes has a clear benefit compared to isolated or disrupted mitochondria due
      to the dynamic interplay between mitochondria and other cellular compartments.
      Platelet mitochondria have a potential to serve as a source of human viable
      mitochondria when studying mitochondrial physiology and pathogenic mechanisms, as
      well as for the diagnostics of mitochondrial diseases. The objective of the
      present study was to perform a detailed evaluation of platelet mitochondrial
      respiration using high-resolution respirometry. Further, we aimed to explore the
      limits of sample size and the impact of storage as well as to establish a wide
      range of reference data from different pediatric and adult cohorts. Our results
      indicate that platelet mitochondria are well suited for ex-vivo analysis with the
      need for minute sample amounts and excellent reproducibility and stability.

PMID- 23164799
TI  - A multi-center comparison of diagnostic methods for the biochemical evaluation of
      suspected mitochondrial disorders.
AB  - A multicenter comparison of mitochondrial respiratory chain and complex V enzyme
      activity tests was performed. The average reproducibility of the enzyme assays is
      16% in human muscle samples. In a blinded diagnostic accuracy test in patient
      fibroblasts and SURF1 knock-out mouse muscle, each lab made the correct diagnosis
      except for two complex I results. We recommend that enzyme activities be
      evaluated based on ratios, e.g. with complex IV or citrate synthase activity. In
      spite of large variations in observed enzyme activities, we show that inter
      laboratory comparison of patient sample test results is possible by using
      normalization against a control sample.

PMID- 23164800
TI  - Edelfosine and perifosine disrupt hepatic mitochondrial oxidative phosphorylation
      and induce the permeability transition.
AB  - Edelfosine and perifosine are alkylphospholipids that have been intensively
      studied as potential antitumor agents. Apoptotic cell death caused by these two
      compounds is mediated, at least in part, through mitochondria. Additionally,
      previous works demonstrated that edelfosine induces changes in mitochondrial
      membrane permeability that are somehow reduced by using cyclosporin A. Therefore,
      the objective of the present study was not only to confirm mitochondrial
      permeability transition but also identify direct effects of both ether lipids on
      mitochondrial hepatic fractions, namely on mitochondrial oxidative
      phosphorylation and generation of hydrogen peroxide (H(2)O(2)) through the
      respiratory chain. Results show that edelfosine and perifosine inhibit
      mitochondrial respiration and decrease transmembrane electric potential. However,
      despite these effects, edelfosine and perifosine were still able to induce
      mitochondrial permeability transition in non-energized mitochondria.
      Interestingly, edelfosine decreased H(2)O(2) production through the respiratory
      chain. In conclusion, the present work demonstrates previously unknown
      alterations of mitochondrial physiology directly induced by edelfosine and
      perifosine. The study is relevant in the understanding of mitochondrial-target
      effects of both compounds, as well as to acknowledge possible toxic responses in
      non-tumor organs.

PMID- 23164801
TI  - Developing outcome measures for pediatric mitochondrial disorders: which
      complaints and limitations are most burdensome to patients and their parents?
AB  - Since some drug intervention effects are only experienced by the patient,
      organizations such as the Food and Drug Administration prefer clinically
      meaningful outcome measures. Here, we evaluated which symptoms and limitations in
      daily life are most burdensome to pediatric patients with mitochondrial disorders
      and their parents, using two questionnaires. In a study of 78 patients, the most
      burdensome complaints included fatigue, behavior and speech disturbances,
      epilepsy and muscle weakness and a high degree of limitations in daily activities
      was found. Importantly, there was a discrepancy between what symptoms metabolic
      pediatricians estimated would be most burdensome compared to the
      patients'/caretakers' opinion. To include feasible and relevant outcome measures
      in intervention studies, the experience and opinions of patients and caretakers
      should therefore be heard.

PMID- 23164802
TI  - Monosomal karyotype predicts poor survival after allogeneic stem cell
      transplantation in chromosome 7 abnormal myelodysplastic syndrome and secondary
      acute myeloid leukemia.
AB  - Treatment algorithms for poor cytogenetic-risk myelodysplastic syndrome (MDS),
      defined by chromosome 7 abnormalities or complex karyotype (CK), include
      allogeneic stem cell transplantation (alloSCT). We studied outcome of alloSCT in
      chromosome 7 abnormal MDS patients as this data are scarce in literature. We
      specifically focused on the impact of the extra presence of CK and monosomal
      karyotype (MK). The European Group for Blood and Marrow Transplantation database
      contained data on 277 adult MDS patients with a chromosome 7 abnormality treated
      with alloSCT. Median age at alloSCT was 45 years. Median follow-up of patients
      alive was 5 years. Five-year progression-free survival (PFS) and overall survival
      (OS) were 22% and 28%, respectively. In multivariate analysis, statistically
      significant predictors for worse PFS were higher MDS stages treated, but not in
      complete remission (CR) (hazards ratio (HR) 1.7), and the presence of CK (HR 1.5)
      or MK (HR 1.8). Negative predictive factors for OS were higher MDS stages
      treated, but not in CR (HR 1.8), and the presence of CK (HR 1.6) or MK (HR 1.7).
      By means of the cross-validated log partial likelihood, MK showed to have a
      better predictive value than CK. The results are relevant when considering
      alloSCT for higher-stage MDS patients having MK including a chromosome 7
      abnormality.

PMID- 23164803
TI  - Proton pump inhibitors significantly increase the intracellular concentration of
      nilotinib, but not imatinib in target CML cells.

PMID- 23164804
TI  - Multi-ethnic cytochrome-P450 copy number profiling: novel pharmacogenetic alleles
      and mechanism of copy number variation formation.
AB  - To determine the role of CYP450 copy number variation (CNV) beyond CYP2D6, 11
      CYP450 genes were interrogated by multiplex ligation-dependent probe
      amplification and quantitative PCR in 542 African-American, Asian, Caucasian,
      Hispanic and Ashkenazi Jewish individuals. The CYP2A6, CYP2B6 and CYP2E1 combined
      deletion/duplication allele frequencies ranged from 2 to 10% in these
      populations. High-resolution microarray-based comparative genomic hybridization
      (aCGH) localized CYP2A6, CYP2B6 and CYP2E1 breakpoints to directly oriented low
      copy repeats. Sequencing localized the CYP2B6 breakpoint to a 529-bp intron 4
      region with high homology to CYP2B7P1, resulting in the CYP2B6*29 partial
      deletion allele and the reciprocal, and novel, CYP2B6/2B7P1 duplicated fusion
      allele (CYP2B6*30). Together, these data identified novel CYP450 CNV alleles
      (CYP2B6*30 and CYP2E1*1Cx2) and indicate that common CYP450 CNV formation is
      likely mediated by non-allelic homologous recombination resulting in both full
      gene and gene-fusion copy number imbalances. Detection of these CNVs should be
      considered when interrogating these genes for pharmacogenetic drug selection and
      dosing. 

PMID- 23164805
TI  - Human papillomavirus proteins as prospective therapeutic targets.
AB  - Human papillomaviruses (HPV) are the causative agents of a subset of cervical
      cancers that are associated with persistent viral infection. The HPV genome is an
      ~8 kb circle of double-stranded DNA that encodes eight viral proteins, among
      which the products of the E6 and E7 open reading frames are recognized as being
      the primary HPV oncogenes. E6 and E7 are expressed in pre-malignant lesions as
      well as in cervical cancers; hence these proteins have been extensively studied
      as potential targets for HPV therapies and novel vaccines. Here we review the
      expression and functions of E6 and E7 in the viral vegetative cycle and in
      oncogenesis. We also explore the expression and functions of other HPV proteins,
      including those with oncogenic properties, and discuss the potential of these
      molecules as alternative therapeutic targets.

PMID- 23164806
TI  - Provision of vascular surgery in England in 2012.
AB  - INTRODUCTION: In 2009 the Vascular Society of Great Britain and Ireland reported
      its recommendations for The Provision of Vascular Services for Patients with
      Vascular Disease. The objective is to halve the UK elective surgery mortality
      rate for Abdominal Aortic Aneurysm to 3.5% by 2013. From 16th March 2012,
      statutory approval has been given by Parliament to recognise Vascular Surgery as
      a Specialty in the UK. This study assesses the provision of vascular surgery in
      acute trusts across England. METHOD: From the Department of Health, 169 acute
      trusts were identified in England and each acute trust was emailed under the
      Freedom of Information Act. RESULTS: There was a 98.8% response rate. There are
      currently 80 trusts in England providing acute and elective arterial and aortic
      surgery, with 48 vascular hubs and 32 trusts which either provide a local on call
      network or are currently under review. Within the 48 vascular hubs there are a
      mean of 4.8 consultants and 3.75 middle grades. The on call rota was on average a
      1 in 6. CONCLUSION: This study has shown that currently 80 trusts in England
      provide acute and elective arterial and aortic surgery with 48 centralised
      complex and arterial vascular services. An integrated vascular service will
      provide the best quality of care, develop the latest techniques and improve
      clinical standards.

PMID- 23164807
TI  - Successful treatment by transcatheter aortic valve implantation of severe aortic
      regurgitation in a patient with ascending aorta prosthesis.
AB  - Severe aortic regurgitation (AR), when intervention is required, is managed by
      surgical aortic valve replacement (SAVR). Recently, transcatheter aortic valve
      replacement (TAVR) for severe aortic stenosis (AS) has shown non-inferiority to
      SAVR and superiority to medical management. TAVR could be a valid "off label"
      option to treat severe AR for patients unsuitable for SAVR due to their high
      surgical risk. Among aortic pathologies leading to severe AR, those involving the
      aortic root are considered as high risk procedures and thus prohibit TAVR. For
      these reasons TAVR is not an option for severe AR due to concomitant aortic root
      dilatation and degeneration. We report a successful case of TAVR for severe AR
      due to dilatation of degenerated tract of aortic root.

PMID- 23164808
TI  - Mechanisms of network collapse in GeO2 glass: high-pressure neutron diffraction
      with isotope substitution as arbitrator of competing models.
AB  - The structure of the network forming glass GeO(2) is investigated by making the
      first application of the method of in situ neutron diffraction with isotope
      substitution at pressures increasing from ambient to 8 GPa. Of the various
      models, the experimental results are in quantitative agreement only with
      molecular dynamics simulations made using interaction potentials that include
      dipole-polarization effects. When the reduced density rho/rho(0) > or
      approximately equal to 1.16, where rho(0) is the value at ambient pressure,
      network collapse proceeds via an interplay between the predominance of distorted
      square pyramidal GeO(5) units versus octahedral GeO(6) units as they replace
      tetrahedral GeO(4) units. This replacement necessitates the formation of
      threefold coordinated oxygen atoms and leads to an increase with density in the
      number of small rings, where a preference is shown for sixfold rings when
      rho/rho(0) = 1 and fourfold rings when rho/rho(0) = 1.64.

PMID- 23164809
TI  - The importance of biomarkers in neonatology.
AB  - Despite a 35% decline in the mortality rate for infants aged <5 years over the
      past two decades, every year nearly 40% of all deaths in this age group occur in
      the neonatal period, defined as the first 28 days of life. New knowledge on
      molecular and biochemical pathways in neonatal diseases will lead to the
      discovery of new candidate biomarkers potentially useful in clinical practice. In
      the era of personalized medicine, biomarkers may play a strategic role in
      accelerating the decline in neonatal mortality by assessing the risk of
      developing neonatal diseases, by implementing tailored therapeutic treatment, and
      by predicting the clinical outcome. However, there is an urgent need to reduce
      the gap in translating newly acquired knowledge from bench to bedside.
      Traditional and candidate biomarkers for neonatal sepsis and necrotizing
      enterocolitis will be discussed in this review, such as C-reactive protein (CRP),
      procalcitonin (PCT), serum amyloid A (SAA), soluble form of CD14 subtype
      presepsin (sCD14-ST), lipolysaccharide binding protein (LBP), angiopoietins (Ang)
      1 and -2, soluble form of triggering receptor expressed on myeloid cells (sTREM
      1), soluble form of urokinase-type plasminogen activator receptor (suPAR),
      platelet-activating factor (PAF) and calprotectin. New frontiers in managing
      critically ill newborns may be opened by metabolomics, a diagnostic tool based on
      the recognition of metabolites contained in biological fluids. Metabolomics
      represents the passage from a descriptive science to a predictive science, having
      the potential to translate benchtop research to real clinical benefits.

PMID- 23164810
TI  - Metabolic and mitochondrial effects of antiretroviral drug exposure in pregnancy
      and postpartum: implications for fetal and future health.
AB  - Antiretroviral drugs (ARVs) are indispensable in the treatment and prevention of
      human immunodeficiency virus infection. Although their use before, during and
      after pregnancy is considered safe for mother and child, there are still
      lingering concerns about their long-term health consequences and the
      ramifications of their effects on lipid, glucose, intermediary and mitochondrial
      metabolism. This article reviews the known effects of ARVs on macromolecular and
      mitochondrial metabolism as well as the potential maternal, fetal, neonatal and
      adult health risks associated with abnormal energy metabolism during gestation.
      Recommendations about enhanced monitoring for these risks in affected populations
      are being provided.

PMID- 23164811
TI  - The effects of size and synthesis methods of gold nanoparticle-conjugated
      MalphaHIgG4 for use in an immunochromatographic strip test to detect brugian
      filariasis.
AB  - This study describes the properties of colloidal gold nanoparticles (AuNPs) with
      sizes of 20, 30 and 40 nm, which were synthesized using citrate reduction or
      seeding-growth methods. Likewise, the conjugation of these AuNPs to mouse anti
      human IgG(4) (MalphaHIgG(4)) was evaluated for an immunochromatographic (ICG)
      strip test to detect brugian filariasis. The morphology of the AuNPs was studied
      based on the degree of ellipticity (G) of the transmission electron microscopy
      images. The AuNPs produced using the seeding-growth method showed lower
      ellipticity (G <= 1.11) as compared with the AuNPs synthesized using the citrate
      reduction method (G <= 1.18). Zetasizer analysis showed that the AuNPs that were
      synthesized using the seeding-growth method were almost monodispersed with a
      lower polydispersity index (PDI; PDI<=0.079), as compared with the AuNPs
      synthesized using the citrate reduction method (PDI<=0.177). UV-visible
      spectroscopic analysis showed a red-shift of the absorbance spectra after the
      reaction with MalphaHIgG(4), which indicated that the AuNPs were successfully
      conjugated. The optimum concentration of the BmR1 recombinant antigen that was
      immobilized on the surface of the ICG strip on the test line was 1.0 mg ml(-1).
      When used with the ICG test strip assay and brugian filariasis serum samples, the
      conjugated AuNPs-MalphaHIgG(4) synthesized using the seeding-growth method had
      faster detection times, as compared with the AuNPs synthesized using the citrate
      reduction method. The 30 nm AuNPs-MalphaHIgG(4), with an optical density of 4
      from the seeding-growth method, demonstrated the best performance for labelling
      ICG strips because it displayed the best sensitivity and the highest specificity
      when tested with serum samples from brugian filariasis patients and controls.

PMID- 23164812
TI  - Presence of antiseptic resistance genes in porcine methicillin-resistant
      Staphylococcus aureus.
AB  - Numerous studies have documented the presence of methicillin-resistant
      Staphylococcus aureus (MRSA) in meat-producing animals, which has led to concern
      about its spread into the community. Disinfectants play an important role in
      reduction of contamination in both animal husbandry and food-preparation, helping
      control spread of organisms from foodstuffs, including raw meat. Plasmid-borne
      antiseptic resistance (AR) genes increasing tolerance to several disinfectants
      have been reported in S. aureus of human origin (qacA/B and smr) and from bovine,
      equine, and caprine staphylococcal isolates (qacG, qacH, and qacJ). This study
      investigated the presence of AR genes in porcine MRSA isolates. Plasmid DNA from
      100 MRSA ST9 strains isolated from pig carcasses was amplified for the presence
      of AR genes. Minimum inhibitory concentrations (MICs) and minimum bactericidal
      concentrations (MBCs) to benzalkonium chloride (BC) and chlorhexidine gluconate
      (CHX) were determined in AR gene-positive isolates. qacG was present in 45
      strains, eight of which also harbored smr. No strains carried qacA/B, qacH or
      qacJ. Presence of smr increased MICs to both BC and CHX and MBCs of CHX, but qacG
      presence only resulted in elevated MBC for CHX. This is the first report of AR
      genes from a porcine source. AR gene positivity has previously been associated
      with methicillin resistance and AR gene presence in these strains may increase
      their ability to persist in the environment. Improved implementation of hygiene
      measures during transportation and pre- and post-slaughter should be considered
      to prevent spread in the community.

PMID- 23164813
TI  - Have we been asking the right questions when assessing response inhibition in
      go/no-go tasks with fMRI? A meta-analysis and critical review.
AB  - The popular go/no-go paradigm is supposed to ensure a reliable probing of
      response inhibition mechanisms. Functional magnetic resonance imaging (fMRI)
      studies have repeatedly found a large number of structures, usually including a
      right lateralized parieto-frontal network and the pre-supplementary motor area
      (pre-SMA). However, it is unlikely that all these regions are directly related to
      the mechanism that actively suppresses the motor command. Since most go/no-go
      designs involve complex stimulus identification/detection processes, these
      activations may rather reflect the engagement of different cognitive processes
      that are intrinsically related and quite difficult to disentangle. The current
      critical review is based on repeated meta-analyses of 30 go/no-go fMRI
      experiments using the Activation Likelihood Estimate method to contrast studies
      using simple vs. complex stimuli. The results show that most of the activity
      typically elicited by no-go signals, including pre-SMA hemodynamic response, is
      actually driven by the engagement of high attentional or working memory
      resources, not by inhibitory processes per se. Implications for current methods
      and theories of inhibitory control are discussed, and new lines of inquiry are
      proposed.

PMID- 23164814
TI  - Psychostimulants and motivated behavior: arousal and cognition.
AB  - Motivated, goal-directed behavior requires the coordination of multiple
      behavioral processes that facilitate interacting with the environment, including
      arousal, motivation, and executive function. Psychostimulants exert potent
      modulatory influences on these processes, providing a useful tool for
      understanding the neurobiology of motivated behavior. The neural mechanisms
      underlying the reinforcing effects of psychostimulants have been extensively
      studied over the past 50 years. In contrast, the study of the neurobiology of the
      arousal-enhancing and executive-modulating actions of psychostimulants was only
      initiated relatively recently. This latter work identifies a series of dose
      dependent actions of psychostimulants within a network of prefrontal cortical and
      subcortical sites that coordinate the arousal-promoting and cognition-modulating
      effects of these drugs. These actions are dependent on a variety of catecholamine
      receptor subtypes, including noradrenergic alpha1 and alpha2 receptors and
      dopaminergic D1 receptors. In the prefrontal cortex, psychostimulants exert
      inverted-U shaped modulatory actions that are apparent at the levels of the
      neuron and behavior. Collectively, these observations provide new insight into
      the neurobiology underlying motivated, goal-directed behavior.

PMID- 23164816
TI  - Multiple effects of physical activity on molecular and cognitive signs of brain
      aging: can exercise slow neurodegeneration and delay Alzheimer's disease?
AB  - Western countries are experiencing aging populations and increased longevity;
      thus, the incidence of dementia and Alzheimer's disease (AD) in these countries
      is projected to soar. In the absence of a therapeutic drug, non-pharmacological
      preventative approaches are being investigated. One of these approaches is
      regular participation in physical activity or exercise. This paper reviews
      studies that have explored the relationship between physical activity and
      cognitive function, cognitive decline, AD/dementia risk and AD-associated
      biomarkers and processes. There is now strong evidence that links regular
      physical activity or exercise to higher cognitive function, decreased cognitive
      decline and reduced risk of AD or dementia. Nevertheless, these associations
      require further investigation, more specifically with interventional studies that
      include long follow-up periods. In particular, relatively little is known about
      the underlying mechanism(s) of the associations between physical activity and AD
      neuropathology; clearly this is an area in need of further research, particularly
      in human populations. Although benefits of physical activity or exercise are
      clearly recognised, there is a need to clarify how much physical activity
      provides the greatest benefit and also whether people of different genotypes
      require tailored exercise regimes. 

PMID- 23164815
TI  - Electrographic status epilepticus is associated with mortality and worse short
      term outcome in critically ill children.
AB  - OBJECTIVES: Electrographic seizures and electrographic status epilepticus are
      common in critically ill children. We aimed to determine whether electrographic
      seizures and electrographic status epilepticus are associated with higher
      mortality or worse short-term neurologic outcome. DESIGN: Prospective
      observational study. SETTING: PICU of a tertiary children's hospital. PATIENTS:
      Non-neonatal children admitted to a PICU with acute encephalopathy underwent
      continuous electroencephalographic monitoring. Electroencephalographs were scored
      as 1) no seizures, 2) electrographic seizures, or 3) electrographic status
      epilepticus. Covariates included age, acute neurologic disorder category, prior
      neurodevelopmental status, sex, and electroencephalographic background category.
      Outcomes were mortality and worsening of pediatric cerebral performance category
      from preadmission to PICU discharge. Chi-square analysis, Fisher's exact test,
      and multivariable logistic regression were used to evaluate the associations
      between electrographic seizures or electrographic status epilepticus and
      mortality or short-term neurologic outcome, using odds ratios and 95% confidence
      intervals. INTERVENTIONS: None. MAIN RESULTS: Two hundred children underwent
      continuous electroencephalographic monitoring. Eighty-four (42%) had seizures,
      which were categorized as electrographic seizures in 41 (20.5%) and
      electrographic status epilepticus in 43 (21.5%). Thirty-six subjects (18%) died,
      and 88 subjects (44%) had pediatric cerebral performance category worsening. In
      multivariable analysis, electrographic status epilepticus was associated with an
      increased risk of mortality (odds ratio 5.1; 95% confidence interval 1.4, 18; p =
      0.01) and pediatric cerebral performance category worsening (odds ratio 17.3; 95%
      confidence interval 3.7, 80; p < 0.001), whereas electrographic seizures were not
      associated with an increased risk of mortality (odds ratio 1.3; 95% confidence
      interval 0.3, 5.1; p = 0.74) or pediatric cerebral performance category worsening
      (odds ratio 1.2; 95% confidence interval 0.4, 3.9; p = 0.77). CONCLUSIONS:
      Electrographic status epilepticus, but not electrographic seizures, is associated
      with mortality and worse short-term neurologic outcome in critically ill children
      with acute encephalopathy.

PMID- 23164817
TI  - The protective effect of the obesity-associated rs9939609 A variant in fat mass-
      and obesity-associated gene on depression.
AB  - Candidate gene and genome-wide association studies have not identified common
      variants, which are reliably associated with depression. The recent
      identification of obesity predisposing genes that are highly expressed in the
      brain raises the possibility of their genetic contribution to depression. As
      variation in the intron 1 of the fat mass- and obesity-associated (FTO) gene
      contributes to polygenic obesity, we assessed the possibility that FTO gene may
      contribute to depression in a cross-sectional multi-ethnic sample of 6561
      depression cases and 21,932 controls selected from the EpiDREAM, INTERHEART, DeCC
      (depression case-control study) and Cohorte Lausannoise (CoLaus) studies. Major
      depression was defined according to DSM IV diagnostic criteria. Association
      analyses were performed under the additive genetic model. A meta-analysis of the
      four studies showed a significant inverse association between the obesity risk
      FTO rs9939609 A variant and depression (odds ratio=0.92 (0.89, 0.97), P=3 * 10(
      4)) adjusted for age, sex, ethnicity/population structure and body-mass index
      (BMI) with no significant between-study heterogeneity (I(2)=0%, P=0.63). The FTO
      rs9939609 A variant was also associated with increased BMI in the four studies
      (beta 0.30 (0.08, 0.51), P=0.0064) adjusted for age, sex and ethnicity/population
      structure. In conclusion, we provide the first evidence that the FTO rs9939609 A
      variant may be associated with a lower risk of depression independently of its
      effect on BMI. This study highlights the potential importance of obesity
      predisposing genes on depression.

PMID- 23164819
TI  - Inflammatory and immune response genes have significantly altered expression in
      schizophrenia.

PMID- 23164820
TI  - Genome-wide analysis of rare copy number variations reveals PARK2 as a candidate
      gene for attention-deficit/hyperactivity disorder.
AB  - Attention-deficit/hyperactivity disorder (ADHD) is a common, highly heritable
      neurodevelopmental disorder. Genetic loci have not yet been identified by genome
      wide association studies. Rare copy number variations (CNVs), such as chromosomal
      deletions or duplications, have been implicated in ADHD and other
      neurodevelopmental disorders. To identify rare (frequency <=1%) CNVs that
      increase the risk of ADHD, we performed a whole-genome CNV analysis based on 489
      young ADHD patients and 1285 adult population-based controls and identified one
      significantly associated CNV region. In tests for a global burden of large (>500
      kb) rare CNVs, we observed a nonsignificant (P=0.271) 1.126-fold enriched rate of
      subjects carrying at least one such CNV in the group of ADHD cases. Locus
      specific tests of association were used to assess if there were more rare CNVs in
      cases compared with controls. Detected CNVs, which were significantly enriched in
      the ADHD group, were validated by quantitative (q)PCR. Findings were replicated
      in an independent sample of 386 young patients with ADHD and 781 young population
      based healthy controls. We identified rare CNVs within the parkinson protein 2
      gene (PARK2) with a significantly higher prevalence in ADHD patients than in
      controls (P=2.8 * 10(-4) after empirical correction for genome-wide testing). In
      total, the PARK2 locus (chr 6: 162 659 756-162 767 019) harboured three deletions
      and nine duplications in the ADHD patients and two deletions and two duplications
      in the controls. By qPCR analysis, we validated 11 of the 12 CNVs in ADHD
      patients (P=1.2 * 10(-3) after empirical correction for genome-wide testing). In
      the replication sample, CNVs at the PARK2 locus were found in four additional
      ADHD patients and one additional control (P=4.3 * 10(-2)). Our results suggest
      that copy number variants at the PARK2 locus contribute to the genetic
      susceptibility of ADHD. Mutations and CNVs in PARK2 are known to be associated
      with Parkinson disease.

PMID- 23164822
TI  - Surgical management of large and giant cavernous sinus hemangiomas.
AB  - Cavernous sinus hemangiomas (CSH) are rare vascular tumors within the cavernous
      sinus. Gamma Knife radiosurgery (GKS) is less effective for large and giant CSH
      than for smaller ones. In one of the largest single-institution series reported
      thus far, we present 22 patients with large (3-4 cm-diameter, six patients) and
      giant (>4 cm, 16 patients) CSH treated surgically between 1994 and 2011. We also
      review related reports published since 1999 and further compare the treatment
      outcomes of surgery and radiosurgery. In the present study, a modified Dolenc's
      epidural approach was performed in 18 patients and the intradural approach was
      used in four. Gross total or near-total resection was achieved in 18 patients,
      subtotal resection was achieved in three patients and partial resection was
      achieved in one patient. Postoperative ophthalmoparesis occurred in seven
      patients (two improved, four unchanged to preoperative, one new deficit), and
      decreased visual acuity occurred in one patient. The reviewed literature and our
      experience suggest that surgical treatment of large and giant CSH is a reasonable
      option. A relatively low postoperative morbidity can be achieved with minimal
      disturbance of cranial nerve (CN) III, particularly with early localization and
      preservation of CN VI. GKS could be an adjunct treatment for residual tumor.

PMID- 23164823
TI  - Multiple intracranial metastases from a gastric gastrointestinal stromal tumor.
AB  - Intracranial metastases are rare from gastrointestinal stromal tumor (GIST). We
      report a 60-year-old male with a history of stomach GIST who presented with
      ataxia 2.5 years after a partial gastrectomy. MRI revealed enhancing masses in
      the cerebellum and frontal lobe. A suboccipital craniotomy revealed metastatic
      GIST. With subsequent radiosurgical boost to the resection cavity and frontal
      lobe lesion, the patient is doing well 15 months postoperatively. To our
      knowledge, this is one of only a few reports on cerebral GIST metastases from the
      stomach.

PMID- 23164821
TI  - Clusterin regulates beta-amyloid toxicity via Dickkopf-1-driven induction of the
      wnt-PCP-JNK pathway.
AB  - Although the mechanism of Abeta action in the pathogenesis of Alzheimer's disease
      (AD) has remained elusive, it is known to increase the expression of the
      antagonist of canonical wnt signalling, Dickkopf-1 (Dkk1), whereas the silencing
      of Dkk1 blocks Abeta neurotoxicity. We asked if clusterin, known to be regulated
      by wnt, is part of an Abeta/Dkk1 neurotoxic pathway. Knockdown of clusterin in
      primary neurons reduced Abeta toxicity and DKK1 upregulation and, conversely,
      Abeta increased intracellular clusterin and decreased clusterin protein
      secretion, resulting in the p53-dependent induction of DKK1. To further elucidate
      how the clusterin-dependent induction of Dkk1 by Abeta mediates neurotoxicity, we
      measured the effects of Abeta and Dkk1 protein on whole-genome expression in
      primary neurons, finding a common pathway suggestive of activation of wnt-planar
      cell polarity (PCP)-c-Jun N-terminal kinase (JNK) signalling leading to the
      induction of genes including EGR1 (early growth response-1), NAB2 (Ngfi-A-binding
      protein-2) and KLF10 (Kruppel-like factor-10) that, when individually silenced,
      protected against Abeta neurotoxicity and/or tau phosphorylation. Neuronal
      overexpression of Dkk1 in transgenic mice mimicked this Abeta-induced pathway and
      resulted in age-dependent increases in tau phosphorylation in hippocampus and
      cognitive impairment. Furthermore, we show that this Dkk1/wnt-PCP-JNK pathway is
      active in an Abeta-based mouse model of AD and in AD brain, but not in a tau
      based mouse model or in frontotemporal dementia brain. Thus, we have identified a
      pathway whereby Abeta induces a clusterin/p53/Dkk1/wnt-PCP-JNK pathway, which
      drives the upregulation of several genes that mediate the development of AD-like
      neuropathologies, thereby providing new mechanistic insights into the action of
      Abeta in neurodegenerative diseases. 

PMID- 23164824
TI  - Inter-rater reliability of the A-S-C-O classification system for ischemic stroke.
AB  - Atherosclerosis-small vessel disease-cardiac source-other (A-S-C-O) is a new
      phenotypic system that categorizes stroke according to a combination of etiologic
      characteristics. The purpose of this study was to establish the inter-rater
      reliability of ischemic stroke subtyping by applying A-S-C-O criteria to
      retrospectively reviewed medical records. A total of 419 patients with acute
      ischemic stroke were classified according to A-S-C-O criteria by two stroke
      neurologists independently. Inter-rater reliability was assessed by means of the
      kappa statistic. The neurologists agreed on A-S-C-O subtype diagnosis for only
      190 of the 419 patients (45.3%). The kappa statistics for four stroke phenotypes
      were: (i) atherosclerosis, 0.786; (ii) small vessel disease, 0.798; (iii) cardiac
      source, 0.870; and (iv) other causes, 0.860. All p values were <0.001. Ischemic
      stroke can be reliably described with regard to four etiologic categories using
      the A-S-C-O system based on a review of medical records, whereas the overall
      agreement for stroke subtype diagnosis was only moderate.

PMID- 23164825
TI  - Acute tension pneumocephalus secondary to whole spine pneumorrhachis as an
      unusual presentation of a colon cancer complicated by a transsacral cerebrospinal
      fluid leak.
AB  - A 52-year-old woman who was having chemotherapy for treatment of an
      adenocarcinoma of the colon, was admitted to the emergency department because of
      a moderate neurological impairment. Head CT scan showed bifrontal pneumocephalus
      without fractures or discontinuities of the skull base. A few hours later,
      following the patient's neurologic deterioration, a new CT scan showed tension
      pneumocephalus with air diffusion throughout the posterior cranial fossa and
      cervical spine. Because of air bubbles into the cervical spine, an MRI of the
      entire spinal canal was done. This exam revealed a whole spine pneumorrhachis
      along with a transforaminal air passage through the first right sacral foramen
      and a pyogenic collection anterior to sacral bone. An abdomen CT scan showed a
      massive relapse of the colon cancer and confirmed a hypodense collection
      contiguous to the anterior sacral surface, causing erosion of the sacral bone and
      dural layer with air penetration into the spinal canal. Neurosurgical treatment
      by a lumbosacral laminectomy and duraplasty was followed by tumour removal and
      omental covering of the pelvis. Her neurological symptoms were resolved
      completely. One month later, the patient began adjuvant chemotherapy.

PMID- 23164826
TI  - Acute onset distal symmetrical vasculitic polyneuropathy associated with acute
      hepatitis B.
AB  - Hepatitis B can have varied extrahepatic manifestations involving the skin,
      renal, haematological and nervous systems. Neurological manifestations in
      hepatitis B may take the form of Guillain-Barre syndrome and secondary systemic
      vasculitis-related mononeuritis multiplex. The clinical course of hepatitis B
      related, vasculitis-related neuropathy is usually subacute to chronic and
      clinical evolution is relatively benign. To our knowledge, acute hepatitis B
      associated vasculitis manifesting as acute distal symmetric polyneuropathy has
      not been reported. We report a 60-year-old man who presented with fever, mild
      hepatomegaly, skin lesions in the form of non-palpable purpura and acute onset
      distal symmetric sensorimotor polyneuropathy. Serum transaminase levels were
      raised and viral serological markers revealed acute hepatitis B. The patient
      remained anicteric throughout his clinical course. Nerve conduction studies
      showed severe axonal sensorimotor polyneuropathy and histopathological
      examination of sural nerve biopsy was suggestive of vasculitic neuropathy. The
      patient was first given a course of intravenous immunoglobulin with the antiviral
      drug entecavir. The fever subsided after 1 week of treatment. The patient was
      started on prednisolone in addition to the entecavir, and showed significant
      improvement in motor power and marked resolution in paresthesia after 2 weeks of
      treatment. Thus, acute onset distal symmetric sensorimotor polyneuropathy of
      vasculitic etiology can be a manifestation of acute hepatitis B.

PMID- 23164818
TI  - Common variant at 16p11.2 conferring risk of psychosis.
AB  - Epidemiological and genetic data support the notion that schizophrenia and
      bipolar disorder share genetic risk factors. In our previous genome-wide
      association study, meta-analysis and follow-up (totaling as many as 18 206 cases
      and 42 536 controls), we identified four loci showing genome-wide significant
      association with schizophrenia. Here we consider a mixed schizophrenia and
      bipolar disorder (psychosis) phenotype (addition of 7469 bipolar disorder cases,
      1535 schizophrenia cases, 333 other psychosis cases, 808 unaffected family
      members and 46 160 controls). Combined analysis reveals a novel variant at
      16p11.2 showing genome-wide significant association (rs4583255[T]; odds
      ratio=1.08; P=6.6 * 10(-11)). The new variant is located within a 593-kb region
      that substantially increases risk of psychosis when duplicated. In line with the
      association of the duplication with reduced body mass index (BMI), rs4583255[T]
      is also associated with lower BMI (P=0.0039 in the public GIANT consortium data
      set; P=0.00047 in 22 651 additional Icelanders). 

PMID- 23164827
TI  - Polycranial neuropathy and sensory ataxia with IgG anti-GD1a antibody as a
      variant of Guillain-Barre syndrome.
AB  - Immunoglobulin G (IgG) anti-GD1a ganglioside antibody is an important marker of
      Guillain-Barre syndrome (GBS). This antibody is highly associated with disease
      severity, the need for mechanical ventilation, and axonal degeneration of
      peripheral nerves. We report a 46-year-old female patient manifesting the IgG
      anti-GD1a antibody with polycranial neuropathy and sensory ataxia as a variant of
      GBS. She presented with slurred speech, swallowing difficulties, and gait
      disturbance following diarrhea. Decreased sensations of vibration and position
      were found in her distal limbs and she had an ataxic gait with a positive Romberg
      sign. Her serum was positive for IgG anti-GD1a ganglioside antibody (1:640). Her
      neurological examination at the third month after intravenous Ig treatment showed
      complete recovery.

PMID- 23164828
TI  - Serum uric acid levels and their correlation with clinical and cerebrospinal
      fluid parameters in patients with neuromyelitis optica.
AB  - Although uric acid (UA) concentration has been considered a surrogate marker for
      monitoring the progression of multiple sclerosis (MS), less is known about the
      relationship between UA and the progression of neuromyelitis optica (NMO). We
      therefore investigated the correlations between serum UA concentrations and the
      clinical and cerebrospinal fluid (CSF) parameters in patients with NMO. Factors
      assessed in patients with NMO included gender, disease duration, disease
      disability, CSF white blood cell (WBC) counts, oligoclonal bands (OB), 24 hour
      immunoglobulin (Ig)G index, and myelin basic protein (MBP) concentration. Mean
      serum UA concentrations were compared in patients with NMO and in a control group
      of patients with cerebral infarction (CI). We found that mean serum UA
      concentrations were significantly lower in patients with NMO compared to those
      with CI (206.81 compared to 274.00 MUmol/L, p=0.00). Serum UA concentration was
      correlated directly with NMO duration (p=0.013) and was inversely correlated with
      the Expanded Disability Status Scale score (p=0.021). Patients with NMO with
      lower serum UA concentrations tended to be positive for OB, to have higher CSF
      protein and MBP concentrations, and to have higher WBC counts and 24 hour IgG
      index, but no correlation was statistically significant. UA may be a useful
      surrogate marker for monitoring NMO activity.

PMID- 23164829
TI  - Spinal cord compression in a patient with blue rubber bleb nevus syndrome.
AB  - Blue rubber bleb nevus syndrome is a rare condition characterised by venous
      malformations that affect the gastrointestinal tract and skin. There may be
      involvement of other organs. We describe a 70-year-old male with multiple
      extradural venous malformations resulting in spinal cord compression.

PMID- 23164830
TI  - Response to another comment on Slipped capital femoral epiphysis:  reduction as a
      risk factor for avascular necrosis.

PMID- 23164831
TI  - Bilateral pediatric Kienbock's disease:  a case report.
AB  - Bilateral Kienbock's disease in pediatrics is extremely rare. We report a case of
      a 14-year-old boy with bilateral pediatric Kienbock's disease who was treated by
      temporary scaphotrapeziotrapezoidal joint fixation, with a good clinical result
      and radiographic results.

PMID- 23164832
TI  - Percutaneous reduction and intramedullary fixation technique for displaced
      pediatric radial neck fractures.
AB  - This study investigated the outcome of displaced pediatric radial neck fractures
      treated by percutaneous leverage reduction and intramedullary fixation using
      Kirschner wires. Twenty-three patients with displaced radial neck fractures were
      treated following this technique. Adequate reduction was achieved in each
      patient. Twenty-one patients were followed up for 37 months on average. All
      fractures healed. Malunion occurred in three patients with an average residual
      angulation of 7.3 degrees . According to the MEPI, excellent outcome was achieved
      in 15 patients and good outcome in six. Therefore, this technique is an effective
      alternative for the treatment of pediatric radial neck fractures.

PMID- 23164833
TI  - Shelf acetabuloplasty for Perthes disease in patients older than eight years of
      age:  an observational cohort study.
AB  - This is a retrospective review of 24 patients with late-onset Perthes disease
      treated with shelf acetabuloplasty. The mean age of the patients was 9.8 years.
      The medial joint space ratio improved from 1.66 to 1.47 (P<0.05) and the
      acetabular cover ratio improved from 0.87 to 1.18 (P<0.001). At maturity, five
      hips were Stulberg II, 13 were Stulberg III and six were Stulberg IV. The study
      suggests that shelf acetabuloplasty favourably affects long-term Stulberg grading
      and therefore outcome compared with historic nonoperative treatment regimens. We
      believe that the procedure deserves further evaluation in any future randomized
      controlled trial of the management of late-onset Perthes disease.

PMID- 23164834
TI  - [Tuberculosis of the breast: a rare often unrecognized diagnosis].
AB  - Tuberculosis of the breast (BT) is a rare extrapulmonary localization for
      tuberculosis that mainly affects young women during their child-bearing years.
      OBJECTIVE: We report eight cases of BT and describe its clinical characteristics,
      outcomes, and differential diagnoses. PATIENTS AND METHODS: This retrospective
      study collected all cases of BT diagnosed at our hospital's infectious disease
      department in Tunisia from 2000 through 2009. We assessed the epidemiologic and
      clinical findings and reviewed the laboratory, histology, and radiology results,
      treatment data, and outcomes. RESULTS: Eight women (mean age: 52.5 years, range:
      31-75) had BT. Clinical features included retracted erythematous lesions in four
      cases, a fluctuating abscess in two, and a well-defined nodule in two. The biopsy
      culture was positive in two cases. Histology results showed a tuberculoid
      granuloma with caseous necrosis in all cases. Antituberculosis drugs were
      administered for 8 to 12 months. Two patients underwent surgery. Outcome included
      total regression of BT for all women. CONCLUSION: Clinical features of BT are
      often misleading and can easily be mistaken for those of breast cancer.
      Identification of the Koch bacillus or the presence of a tuberculoid granuloma
      with caseous necrosis on histology facilitates diagnosis. The treatment consists
      essentially of antituberculosis drugs. Despite its rarity, BT must not be
      misjudged, especially in countries where tuberculosis is endemic.

PMID- 23164835
TI  - Bone marrow mononuclear cell therapy in experimental allergic asthma:
      intratracheal versus intravenous administration.
AB  - We hypothesized that the route of administration would impact the beneficial
      effects of bone marrow-derived mononuclear cell (BMDMC) therapy on the
      remodelling process of asthma. C57BL/6 mice were randomly assigned to two main
      groups. In the OVA group, mice were sensitized and challenged with ovalbumin,
      while the control group received saline using the same protocol. Twenty-four
      hours before the first challenge, control and OVA animals were further randomized
      into three subgroups to receive saline (SAL), BMDMCs intravenously (2*10(6)), or
      BMDMCs intratracheally (2*10(6)). The following changes were induced by BMDMC
      therapy in OVA mice regardless of administration route: reduction in resistive
      and viscoelastic pressures, static elastance, eosinophil infiltration, collagen
      fibre content in airways and lung parenchyma; and reduction in the levels of
      interleukin (IL)-4, IL-13, transforming growth factor-beta and vascular
      endothelial growth factor. In conclusion, BMDMC modulated inflammatory and
      remodelling processes regardless of administration route in this experimental
      model of allergic asthma.

PMID- 23164836
TI  - Evaluation of total knee arthroplasty performed with and without computer
      navigation: a bilateral total knee arthroplasty study.
AB  - Sequential bilateral total knee arthroplasty performed on 54 patients utilizing
      navigation (CAS-TKA) in one knee and traditional instrumentation (T-TKA) in the
      contralateral knee was reviewed at a mean follow-up duration of 2.5years. There
      were no differences with regard to KSS, ROM, postoperative anatomic alignment,
      mechanical axis, or tibial angle. There was a statistically significant decrease
      in outliers for the CAS-TKA group with respect to anatomic alignment (3.7% vs.
      17.0%, P=0.024), mechanical axis (6.1 vs. 20.4%, P=0.037) and tibial component
      alignment (0% vs. 7.5%, P=0.042). There is no apparent benefit of CAS-TKA with
      regards to KSS, ROM, or alignment in the hands of fellowship-trained total joint
      specialists. The clinical relevance of reduced outliers in the CAS-TKA group is
      unknown with the current follow-up interval.

PMID- 23164837
TI  - Revision total hip arthroplasty using an alumina-on-alumina bearing surface in
      patients with osteolysis.
AB  - We evaluated the outcomes of 64 consecutive revision total hip arthroplasties
      with an alumina-on-alumina bearing surface in 61 patients with osteolysis. No
      implants had been rerevised nor was osteolysis detected at a mean of 9.8 years
      (range, 7.0-13.1 years) postoperatively. There was 1 case of stem loosening but
      no cup loosening or alumina bearing fractures. Two surgical procedures were
      performed for an infection in 1 patient. Three dislocations occurred in 3 hips;
      all were treated with closed reduction and abduction bracing for 3 months. No
      further dislocations occurred. With any reoperation or radiographic evidence of
      osteolysis or loosening as the end point, the 7-year survival rate was 96.9% (95%
      confidence interval, 90.8%-100%). The alumina-on-alumina bearing surfaces used
      for revision total hip arthroplasty in patients with osteolysis were found to
      produce encouraging clinical results and implant survival rates at a minimum of 7
      years postoperatively.

PMID- 23164838
TI  - Dislocation after total hip arthroplasty: a randomized clinical trial of a
      posterior approach and a modified lateral approach.

PMID- 23164840
TI  - Simultaneous refractive index and temperature measurements using a tapered bend
      resistant fiber interferometer.
AB  - Simultaneous measurements of refractive index (RI) and temperature are proposed
      and experimentally demonstrated by using a tapered bend-resistant fiber
      interferometer. Different phase shifts of an inner and outer cladding mode of the
      fiber interferometer are measured to determine the temperature compensated RI of
      a glycerol solution. The temperature coefficients of the inner and outer cladding
      modes are -0.0253 rad/ degrees C and -0.0523 rad/ degrees C, and the RI
      coefficients are 4.0403 rad/RIU and 44.823 rad/RIU, respectively. The minimum
      errors of temperature and RI are 0.6 degrees C and 0.001 RIU, respectively.

PMID- 23164839
TI  - Production and characterization of a monoclonal antibody against recombinant
      saposin-like protein 2 of Fasciola gigantica.
AB  - A monoclonal antibody (MoAb) against recombinant Fasciola gigantica saposin-like
      protein 2 (rFgSAP-2) was produced by hybridoma technique using spleen cells from
      BALB/c mice immunized with rFgSAP-2. This MoAb is an IgG1, kappa light chain
      isotype. By immunoblotting and indirect ELISA, the MoAb reacted specifically with
      rFgSAP-2, the natural FgSAP-2 at 10kDa in whole body (WB) and excretory-secretory
      (ES) fractions of F. gigantica. It did not cross react with antigens in WB
      fractions from other parasites, including Opisthorchis viverrini, Schistosoma
      mansoni which are human parasites, Haemonchus placei, Setaria labiato-papillosa,
      Eurytrema pancreaticum, Cotylophoron cotylophorum, Fischoederius cobboldi,
      Gigantocotyle explanatum, Gastrothylax crumenifer, and Paramphistomum cervi which
      are ruminant parasites. By immunohistochemistry, the FgSAP-2 protein was
      localized only in the cytoplasm of caecal epithelial cells of 4-week-old juvenile
      and adult stages, but not in metacercariae, newly excysted juvenile (NEJ), 2- and
      3-week-old juveniles. This finding indicated that FgSAP-2 is an abundantly
      expressed parasite protein that is released into the ES, hence SAP-2 and its MoAb
      may be used for immunodiagnosis of ruminant and human fasciolosis.

PMID- 23164841
TI  - Temperature-insensitive fiber-optic devices using multimode interference effect.
AB  - We show theoretically that the fiber-optic devices using single-multi-single mode
      fiber structures can be made temperature insensitive by properly adjusting the
      concentration of P(2)O(5) in the core region of the multimode fiber used. Taking
      an example of a parabolic index multimode fiber, we obtain the temperature
      insensitive transmission spectrum and fiber-optic lens action for a core
      composition of 1.57 mol. % P(2)O(5) and 13.5 mol. % GeO(2) in the SiO(2) host.

PMID- 23164842
TI  - In vivo optical-resolution photoacoustic computed tomography with compressed
      sensing.
AB  - Optical-resolution photoacoustic microscopy is becoming a powerful research tool
      for studying microcirculation in vivo. Moreover, ultrasonic-array-based optical
      resolution photoacoustic computed tomography (OR-PACT), providing comparable
      resolution at an improved speed, has opened up new opportunities for studying
      microvascular dynamics. In this Letter, we have developed a compressed sensing
      with partially known support (CS-PKS) photoacoustic reconstruction strategy for
      OR-PACT. Compared with conventional backprojection reconstruction, the CS-PKS
      strategy was shown to produce high-quality in vivo OR-PACT images with threefold
      less measurement data, which can be leveraged to improve the data acquisition
      speed and costs of OR-PACT systems.

PMID- 23164843
TI  - Wavelength conversion in a highly nonlinear chalcogenide microstructured fiber.
AB  - We report on all-optical wavelength conversion of a 56 Gb/s differential
      quadrature phase shift keying signal and a 42.7 Gb/s on-off keying signal.
      Wavelength conversion is based on four-wave mixing effect in a 1 m long highly
      nonlinear GeAsSe chalcogenide fiber. The high nonlinearity of the fiber allows
      low-power penalty operation with a total average power of less than 60 mW.

PMID- 23164844
TI  - Low-power plasmon-soliton in realistic nonlinear planar structures.
AB  - We study the propagation of nonlinear waves in layered nonlinear
      dielectric/linear dielectric/metal planar structures. We develop vector models
      that describe the light propagation in such configurations and allow us to obtain
      both one- and two-dimensional solutions. We compute the nonlinear dispersion
      relation and the field profiles, and estimate losses. We use our models to design
      realistic structures, in terms of linear and nonlinear properties, which support
      soliton waves with a plasmon tail at low peak power around or below 1 GW/cm(2).
      These results open the way for potential observation of such states in
      chalcogenide waveguides associated with silica and metal films. In the proposed
      structures, the nonlinearity confines the field in both transverse directions. A
      recordable plasmonic part of the field extends in air.

PMID- 23164845
TI  - Fabry-Perot-based surface plasmon resonance sensors.
AB  - A new sensing approach based on the use of an optical Fabry-Perot (FP) cavity in
      conjunction with surface plasmon resonance (SPR) is proposed and theoretically
      investigated. The impact of the SPR on the intensity and phase response of the
      proposed sensor structure is evaluated using a modified FP model that takes into
      account the SPR effect. Compared to the conventional optical-phase-detection
      based Kretschmann configuration, the proposed sensing approach requires only the
      measurement of the output power spectrum over a narrow wavelength span of several
      nanometers to evaluate the phase responses of the sensor, making it more
      attractive for practical high-sensitivity sensing applications.

PMID- 23164846
TI  - Optimization of the storage capacity of slow light photonic crystal waveguides.
AB  - The storage capacity of slow light photonic crystal waveguides is maximized using
      a systematic procedure based on the optimization of various parameters of the
      structure. Both optical loss and dispersion-induced broadening are incorporated
      into the model. The results indicate that this procedure can provide up to a
      threefold increase in storage capacity.

PMID- 23164848
TI  - Double-pulse and calibration-free laser-induced breakdown spectroscopy at low
      ablative energies.
AB  - The use of double-pulse laser-induced breakdown spectroscopy (DP-LIBS) in
      quantitative analysis generally depends on standards and calibration curves. To
      our knowledge, in this Letter, we report the first quantitative analysis based on
      DP-LIBS at low ablative energies with a self-calibrated method. We compare the
      effects of plasmas on the calibration-free LIBS technique, generated by DP-LIBS,
      and the traditional single-pulse (SP) LIBS on a steel sample. Our analyses reveal
      that when SP-LIBS and DP-LIBS reach comparable emission line intensities, plasma
      parameters and quantitative analysis are practically the same for both
      experiments. Additionally, we report the behavior of the emission enhancement of
      some elements (Fe and Cr) at low ablative pulse energies (0.2-8 mJ) using the
      orthogonal reheating DP-LIBS configuration.

PMID- 23164847
TI  - Near-infrared characterization of gallium nitride photonic-crystal waveguides and
      cavities.
AB  - We report the design and optical characterization of fully suspended wire
      waveguides and photonic crystal (PhC) membranes fabricated on a gallium nitride
      layer grown on silicon substrate operating at 1.5 MUm. W1-type PhC waveguides are
      coupled with suspended wires and are investigated using a standard end-fire
      setup. The experimental and theoretical dispersion properties of the propagating
      modes in the wires and photonic-crystal waveguides are shown. Modified L3
      cavities with quality factors of up to 2200 and heterostructure cavities with
      quality factors of up to 5400 are experimentally demonstrated.

PMID- 23164849
TI  - On the time evolution of the cloaking effect of a metamaterial slab.
AB  - We investigated the time evolution of the cloaking behavior of a small particle
      placed in front of a meta-material slab with epsilon=MU=-1+idelta. We found that
      the dipole excitation would be suppressed in the long time limit. While on the
      way to being cloaked, the excitation will exhibit oscillatory behavior as the
      result of the interference between particle-slab resonances and high density-of
      states surface modes.

PMID- 23164850
TI  - Concentration dependence of upconversion emission from Er:YAG fibers.
AB  - Fibers of Er:YAG have been grown using the laser-heated pedestal growth method.
      Fibers with Er concentrations ranging from 0.5 to 10 mol. % have been produced
      and excitation at 965 nm has been used to produce intense upconversion emission
      at green and red wavelengths. The dependence of ground state absorption and
      upconversion emission on dopant concentration has been studied and shown to
      exhibit lower levels of self-absorption than previously reported. At Er
      concentrations of 5 mol. % and above; however, the variation of upconversion
      emission intensity with pump power deviates from theoretical predictions,
      exhibiting saturation behavior consistent with concentration quenching.

PMID- 23164851
TI  - Discrete solitons in coupled active lasing cavities.
AB  - We examine the existence and stability of discrete spatial solitons in coupled
      nonlinear lasing cavities (waveguide resonators), addressing the case of active
      defocusing media, where the gain exceeds damping in the low-amplitude limit. A
      new family of stable localized structures is found: these are bright and gray
      cavity solitons representing the connections between homogeneous and
      inhomogeneous states. Solitons of this type can be controlled by discrete
      diffraction and are stable when the bistability of homogenous states is absent.

PMID- 23164852
TI  - Polarization effects on contrast in structured illumination microscopy.
AB  - In this Letter, we present an analysis of the effects of polarization state on
      the pattern contrast in a structured illumination microscope. Using vectorial ray
      tracing methods, we show that the contrast varies nonmonotonically with both the
      numerical aperture of the microscope objective lens and the orientation of the
      electric field with respect to the meridional plane. By careful selection of
      these two parameters, high pattern contrast can be obtained without polarization
      rotation, reducing the cost and complexity of structured illumination imaging
      systems and increasing light throughput and imaging speed. We present
      experimental results that show good agreement with theoretical predictions and
      discuss the implications for super-resolution imaging.

PMID- 23164853
TI  - Simultaneous photoacoustic and optically mediated ultrasound microscopy: phantom
      study.
AB  - An experimental setup for combined photoacoustic (PA) and optically mediated
      ultrasound (US) microscopy is presented. A spherically focused 35 MHz
      polyvinylidene fluoride (PVDF) ultrasonic detector with a numerical aperture of
      0.28, a focal distance of 9 mm, and a bandwidth (-6 dB level) of 24 MHz was used
      to obtain PA and US data with a 3 mm imaging depth. A fiber-optic system was
      employed to deliver laser excitation pulses from a tunable laser to the studied
      medium. A single optical pulse was used to form both PA and US A-scans. The
      probing US pulses were generated thermoelastically due to absorption of
      backscattered laser radiation by the metalized surface of a PVDF film.

PMID- 23164854
TI  - Exploring the spatio-temporal dynamics of an optically pumped semiconductor laser
      with intracavity second harmonic generation.
AB  - We experimentally observe an intriguing phenomenon of complex spatio-temporal
      dynamics in a commercial optically pumped semiconductor laser with intracavity
      second harmonic generation. We numerically verify that the experimental results
      come from the total mode locking of transverse electromagnetic modes
      (TEM<sub>00</sub>) and higher-order modes with significant astigmatism. The
      scenarios of the spatio-temporal dynamics are quite similar to the phenomena in
      soft-aperture Kerr-lens mode locked Ti:sapphire lasers.

PMID- 23164855
TI  - Higher-order Kerr effect and harmonic cascading in gases.
AB  - The higher-order Kerr effect (HOKE) has recently been advocated to explain
      measurements of the saturation of the nonlinear refractive index in gases. Here
      we show that cascaded third-harmonic generation results in an effective fifth
      order nonlinearity that is negative and significant. Higher-order harmonic
      cascading will also occur from the HOKE, and the cascading contributions may
      significantly modify the observed nonlinear index change. At lower wavelengths,
      cascading increases the HOKE saturation intensity, while for longer wavelengths
      cascading will decrease the HOKE saturation intensity.

PMID- 23164856
TI  - Compact hybrid plasmonic polarization rotator.
AB  - We propose a novel ultracompact (5 MUm) hybrid plasmonic polarization rotator
      operating at telecommunication wavelength for integrated silicon photonic
      circuits. The polarization mode of a silicon waveguide is rotated with >14 dB
      polarization extinction ratio and low total insertion losses of 2.1 dB.

PMID- 23164857
TI  - Optimization and phase matching of fiber-laser-driven high-order harmonic
      generation at high repetition rate.
AB  - High-repetition-rate sources are very attractive for high-order harmonic
      generation (HHG). However, due to their pulse characteristics (low energy, long
      duration), those systems require a tight focusing geometry to achieve the
      necessary intensity to generate harmonics. In this Letter, we investigate
      theoretically and experimentally the optimization of HHG in this geometry, to
      maximize the extreme UV (XUV) photon flux and improve the conversion efficiency.
      We analyze the influence of atomic gas media (Ar, Kr, or Xe), gas pressure, and
      interaction geometries (a gas jet and a finite and a semi-infinite gas cell).
      Numerical simulations allow us to define optimal conditions for HHG in this tight
      focusing regime and to observe the signature of on-axis phase matching. These
      conditions are implemented experimentally using a high-repetition-rate Yb-doped
      fiber laser system. We achieve optimization of emission with a recorded XUV
      photon flux of 4.5*10(12) photons/s generated in Xe at 100 kHz repetition rate.

PMID- 23164858
TI  - Preserving a diffraction-limited beam in Ho:YAG laser using coherent polarization
      locking.
AB  - We overcome several thermal issues present in Ho:YAG lasers by distributing the
      gain over a larger volume and achieve a diffraction-limited beam using coherent
      polarization locking. Increased single-pass absorption, suppression of output
      power saturation, and improvement in beam quality were shown using the coherent
      polarization locking technique as compared to a conventional Ho:YAG laser cavity
      with the same pump and cavity configuration. Ten watts of CW Ho:YAG laser power
      was generated with >96% coherent combining efficiency.

PMID- 23164860
TI  - Visualizing orbital angular momentum of plasmonic vortices.
AB  - Plasmonic vortices (PVs) are generated by focusing a radially polarized optical
      vortex (OV) beam onto a metal surface. The intensity distribution of the PV is
      registered with a near-field scanning optical microscopy and agrees well with a
      theoretical prediction as well as numerical calculation. Beside the dark central
      spot, the numerical calculation also shows an azimuthal Poynting vector belonging
      to the PV, implying that the orbital angular momentum (OAM) was transferred from
      the radially polarized OV. To directly verify the OAM, plasmonic trapping
      experiments with gold micrometer particles are performed and the particle
      rotation is visualized. Further experiments by varying the topological charge of
      radially polarized OVs show the corresponding changes in rotation in terms of
      speed and radius.

PMID- 23164859
TI  - Diffractive chains of plasmonic nanolenses: combining near-field focusing and
      collective enhancement mechanisms.
AB  - We study, by means of full-electrodynamic calculations using the layer-multiple
      scattering method, the effect of diffractive coupling on the enhancement of the
      local electromagnetic field in periodic arrays of nanolenses consisting of three
      silver spheres with progressively decreasing sizes and separations. The
      interaction between the hot-spot modes of an isolated nanolens with the Rayleigh
      Wood anomalies of the periodic lattice leads to a further enhancement of the
      local field intensity, which can be controlled by an appropriate choice of the
      geometrical parameters involved.

PMID- 23164861
TI  - Tunable, continuous-wave Ti:sapphire channel waveguide lasers written by
      femtosecond and picosecond laser pulses.
AB  - Fabrication and cw lasing at 798.25 nm is reported for femtosecond (fs) and
      picosecond (ps) laser-inscribed channel waveguides in Ti:sapphire crystals.
      Lasing in channels written by fs (ps) pulses was obtained above a threshold of 84
      mW (189 mW) with a maximum output power and a slope efficiency of 143 mW (45 mW)
      and 23.5% (7.1%), respectively. The emission wavelength was tuned over a 170 nm
      range by using a birefringent filter in an external cavity.

PMID- 23164862
TI  - 201 W picosecond green laser using a mode-locked fiber laser driven cryogenic
      Yb:YAG amplifier system.
AB  - We have generated 201 W of green (514.5 nm) average power from a frequency
      doubled picosecond cryogenic Yb:YAG laser system driven by a 50 MHz, 12.4 ps mode
      locked Yb fiber laser producing 430 W of average power at 1029 nm, using direct
      pulse amplification. The fundamental beam produced was near-diffraction-limited
      (M(2)<1.3). Second-harmonic-generation is achieved using a 20 mm long
      noncritically phase-matched Lithium triborate (LiB3O5) crystal; conversion
      efficiencies as high as 58% have been observed. At 100 W of 514.5 nm output
      power, the average M(2) value was 1.35. To the best of our knowledge, this is the
      highest average power picosecond green pulsed laser.

PMID- 23164863
TI  - Microwave spectral analysis based on photonic compressive sampling with random
      demodulation.
AB  - In this Letter, we present a photonic compressive sampling scheme based on
      optical sampling and random demodulation for microwave spectral analysis. A novel
      (to our knowledge) approach to realizing the multiplication of a pseudorandom
      binary sequence and the input microwave signal of interest in the optical domain
      is proposed, which largely simplifies the implementation of the compressive
      sampling. A spectrally sparse signal can be successfully captured by an
      electrical digitizer with a sampling rate much lower than the Nyquist rate with
      the help of random demodulation and the sparse reconstruction algorithm.
      Identification of the signals with multiple frequency components is successfully
      demonstrated.

PMID- 23164864
TI  - Octave-spanning infrared supercontinuum generation in robust chalcogenide
      nanotapers using picosecond pulses.
AB  - We report on infrared supercontinuum generation extending over more than one
      octave of bandwidth, from 850 nm to 2.35 MUm, produced in a single spatial mode
      from a robust, compact, composite chalcogenide glass nanotaper. A picosecond
      laser at 1.55 MUm pumps a high-index-contrast, all-solid nanotaper that strongly
      confines the field to a 480 nm diameter core, while a thermally compatible built
      in polymer jacket lends the nanotaper mechanical stability.

PMID- 23164865
TI  - Raman detection of cell proliferation probes with antiresonance-guiding hollow
      fibers.
AB  - Antiresonance-guiding hollow-core fibers are shown to enable highly sensitive
      detection of cell proliferation probes using Raman scattering within the region
      where the cellular Raman activity is minimal. We demonstrate that such fibers can
      substantially reduce the level of the background compared to standard index
      guiding optical fibers, thus radically improving the sensitivity of Raman
      detection of DNA synthesis in cells and offering a powerful tool for fiber-based
      live-cell imaging.

PMID- 23164866
TI  - Shape-induced anisotropy of intraband luminescence from a semiconductor
      nanocrystal.
AB  - Nonspherical semiconductor nanocrystals (NCs) may exhibit strongly anisotropic
      photoluminescence due to the intraband transitions, whose matrix elements depend
      critically on the envelope wave functions of the confined electrons and holes. We
      demonstrate that this anisotropy may be used as the basis for a new type of
      polarization spectroscopy, enabling one to reliably determine the shape and
      spatial orientation of individual NCs, as well as providing important information
      on the symmetry of quantum states involved in optical transitions.

PMID- 23164867
TI  - Guided-mode resonance filter with high-index substrate.
AB  - We report that a narrow guided-mode resonance (GMR) filter with high-index
      substrate can be achieved by introducing an added layer on the substrate. For
      this type of GMR filter, the refractive index and thickness of the added layer
      are the critical parameters for the GMR effect to occur. We demonstrate that this
      filter has good fabrication tolerances for the grating thickness and fill factor.
      Our design may promote the application of GMR filters in practice.

PMID- 23164868
TI  - Direct nanopatterning of 100 nm metal oxide periodic structures by Deep-UV
      immersion lithography.
AB  - Deep-UV lithography using high-efficiency phase mask has been developed to print
      100 nm period grating on sol-gel based thin layer. High efficiency phase mask has
      been designed to produce a high-contrast interferogram (periodic fringes) under
      water immersion conditions for 244 nm laser. The demonstration has been applied
      to a new developed immersion-compatible sol-gel layer. A sol-gel photoresist
      prepared from zirconium alkoxides caped with methacrylic acids was developed to
      achieve 50 nm resolution in a single step exposure. The nanostructures can be
      thermally annealed into ZrO(2). Such route considerably simplifies the process
      for elaborating nanopatterned surfaces of transition metal oxides, and opens new
      routes for integrating materials of interest for applications in the field of
      photocatalysis, photovoltaic, optics, photonics or microelectronics.

PMID- 23164869
TI  - Microwave collimation based on zero index metamaterials with Dirac point.
AB  - The microwave zero index metamaterials (ZIMs) can be realized by loading lumped
      elements into two-dimensional transmission lines (TLs) with Dirac cones whose
      linear dispersion can appear around the center of the Brillouin zone. Based on
      Snell's law, the refracted angle of waves nearly equals zero when a point source
      radiates from the ZIM TL into the double positive (DPS) one in the ZIM-DPS TL
      structure. Experimental results demonstrate that at Dirac point the curved
      wavefronts in the ZIM region are transformed into planar ones in DPS region.

PMID- 23164870
TI  - Neck instability of bright solitons in normally dispersive Kerr media.
AB  - The neck instability of bright solitons of the hyperbolic nonlinear Shrodinger
      equation is investigated. It is shown that this instability originates from a
      four-wave mixing interaction that links on-axis to off-axis radiation at opposite
      frequency bands. Our experiment supports this interpretation.

PMID- 23164871
TI  - All-optical Brillouin dynamic grating generation in few-mode optical fiber.
AB  - We report, for the first time (to our knowledge), generation of Brillouin dynamic
      gratings (BDGs) in few-mode optical fibers. A moving acoustic grating is
      generated by stimulated Brillouin scattering using a writing beam in one fiber
      mode, which is used to reflect a reading beam at a different wavelength in
      another fiber mode. With single-end pumping, a BDG with a tunable reflectance of
      up to 0.1% is demonstrated in a 15 km specially designed two-mode optical fiber.

PMID- 23164872
TI  - Polarization control of multiply scattered light through random media by
      wavefront shaping.
AB  - We show that the polarization state of coherent light propagating through an
      optically thick multiple scattering medium can be controlled by wavefront
      shaping, that is, by controlling only the spatial phase of the incoming field
      with a spatial light modulator. Any polarization state of light at any spatial
      position behind the scattering medium can be attained with this technique. Thus,
      transforming the random medium to an arbitrary optical polarization component
      becomes possible.

PMID- 23164873
TI  - Monolithic active-passive 16 * 16 optoelectronic switch.
AB  - We present what is to our knowledge the first active-passive monolithically
      integrated 16*16 switch. The active InP/InGaAsP elements provide semiconductor
      optical amplifier gates in a multistage rearrangeably nonblocking switch design.
      Thirty-two representative connections, including the shortest, longest, and
      comprehensive range of intermediate paths have been assessed across the switch
      circuit. The 10 Gb/s signal routing is demonstrated with an optical signal-to
      noise ratio up to 28.3 dB/0.1 nm and a signal extinction ratio exceeding 50 dB.

PMID- 23164874
TI  - Two-step phase demodulation algorithm based on the extreme value of interference.
AB  - Using the maximum and the minimum of interference, a novel two-step phase
      demodulation algorithm is proposed to perform the phase extraction in phase
      shifting interferometry. By means of the simulation calculation and the
      experimental research, it is proved that both the measured phase and the phase
      shift with high precision can be obtained in the proposed algorithm.

PMID- 23164875
TI  - Tuning operating point of extrinsic Fabry-Perot interferometric fiber-optic
      sensors using microstructured fiber and gas pressure.
AB  - Intensity-based demodulation of extrinsic Fabry-Perot interferometric (EFPI)
      fiber-optic sensors requires the light wavelength to be on the quadrature point
      of the interferometric fringes for maximum sensitivity. In this Letter, we
      propose a novel and remote operating-point tuning method for EFPI fiber-optic
      sensors using microstructured fibers (MFs) and gas pressure. We demonstrated the
      method using a diaphragm-based EFPI sensor with a microstructured lead-in fiber.
      The holes in the MF were used as gas channels to remotely control the gas
      pressure inside the Fabry-Perot cavity. Because of the deformation of the
      diaphragm with gas pressure, the cavity length and consequently the operating
      point can be remotely tuned for maximum sensitivity. The proposed operating-point
      tuning method has the advantage of reduced complexity and cost compared to
      previously reported methods.

PMID- 23164876
TI  - Compressive sensing of sparse radio frequency signals using optical mixing.
AB  - We demonstrate an optical mixing system for measuring properties of sparse radio
      frequency (RF) signals using compressive sensing (CS). Two types of sparse RF
      signals are investigated: (1) a signal that consists of a few 0.4 ns pulses in a
      26.8 ns window and (2) a signal that consists of a few sinusoids at different
      frequencies. The RF is modulated onto the intensity of a repetitively pulsed,
      wavelength-chirped optical field, and time-wavelength-space mapping is used to
      map the optical field onto a 118-pixel, one-dimensional spatial light modulator
      (SLM). The SLM pixels are programmed with a pseudo-random bit sequence (PRBS) to
      form one row of the CS measurement matrix, and the optical throughput is
      integrated with a photodiode to obtain one value of the CS measurement vector.
      Then the PRBS is changed to form the second row of the mixing matrix and a second
      value of the measurement vector is obtained. This process is performed 118 times
      so that we can vary the dimensions of the CS measurement matrix from 1*118 to
      118*118 (square). We use the penalized l(1) norm method with stopping parameter
      lambda (also called basis pursuit denoising) to recover pulsed or sinusoidal RF
      signals as a function of the small dimension of the measurement matrix and
      stopping parameter. For a square matrix, we also find that penalized l(1) norm
      recovery performs better than conventional recovery using matrix inversion.

PMID- 23164877
TI  - Optical modes in oxide-apertured micropillar cavities.
AB  - We present a detailed experimental characterization of the spectral and spatial
      structure of the confined optical modes for oxide-apertured micropillar cavities,
      showing good-quality Hermite-Gaussian profiles, easily mode-matched to external
      fields. We further derive a relation between the frequency splitting of the
      transverse modes and the expected Purcell factor. Finally, we describe a
      technique to retrieve the profile of the confining refractive index distribution
      from the spatial profiles of the modes.

PMID- 23164878
TI  - Using carrier-depletion silicon modulators for optical power monitoring.
AB  - Defect-mediated subbandgap absorption is observed in ion-implanted silicon-on
      oxide waveguides that experience a rapid thermal annealing at 1075 degrees C.
      With this effect, general carrier-depletion silicon modulators exhibit the
      capability of optical power monitoring. Responsivity is measured to be 22 mA/W
      for a 3 mm long Mach-Zehnder modulator of 2*10(18) cm(-3) doping concentration at
      -7.1 V bias voltage and 5.9 mA/W for a ring modulator of 1*10(18) cm(-3) doping
      concentration at -10 V bias voltage. The former is used to demonstrate data
      detection of up to 35 Gbits/s.

PMID- 23164879
TI  - Phase conjugation and slow light in dye-doped chiral nematics.
AB  - Optical phase conjugation and slow light are obtained in dye-doped chiral
      nematics via degenerate four-wave mixing. The creation of the light-induced
      dynamical grating is described and the amplitude of the phase-conjugate wave is
      shown to follow the changes of the input signal, hence providing efficient
      distortion correction. Associated to these capabilities, slowing down of light
      pulses is obtained thanks to the dispersive properties of the wave mixing
      occurring in the cholesteric liquid crystals, opening the way to applications in
      interferometry and imaging through highly scattering media.

PMID- 23164880
TI  - Beam-quality measurements using a spatial light modulator.
AB  - We present a fast and easy technique for measuring the beam propagation ratio,
      M(2), of laser beams using a spatial light modulator. Our technique is based on
      digitally simulating the free-space propagation of light, thus eliminating the
      need for the traditional scan in the propagation direction. We illustrate two
      approaches to achieving this, neither of which requires any information of the
      laser beam under investigation nor necessitates any moving optical components.
      The comparison with theoretical predictions reveals excellent agreement and
      proves the accuracy of the technique.

PMID- 23164881
TI  - Fiber-based multiple-access ultrastable frequency dissemination.
AB  - We demonstrate a fiber-based multiple-access ultrastable frequency dissemination
      scheme over an 83 km fiber link. As a performance test, we reproduce the
      disseminated 9.1 GHz radio-frequency modulation signal at an arbitrary point in
      the dissemination channel. Relative frequency stability of 7*10(-14)/s and 5*10(
      18)/day is obtained. Highly synchronized frequency signals can be regenerated
      along the entire fiber pathway and its applications are discussed.

PMID- 23164882
TI  - Simple method to characterize nonlinear refraction and loss in optical
      waveguides.
AB  - We describe a technique for accurately measuring the ratio between the imaginary
      and real parts of the third-order nonlinearity in optical waveguides. Unlike most
      other methods, it does not depend on precise knowledge of the coupling
      efficiencies, optical propagation loss, or optical pulse shape. We apply the
      method to characterize a silicon waveguide, a GaAs waveguide, and AlGaAs
      waveguides with different alloy concentrations.

PMID- 23164883
TI  - Controlling cavity solitons by means of photorefractive soliton electro
      activation.
AB  - We consider a hybrid system consisting of a centrosymmetric photorefractive
      crystal in contact with a vertical-cavity surface-emitting laser. We numerically
      investigate the generation and control of cavity solitons (CSs) by propagating a
      plane wave through electro-activated solitonic waveguides in the crystal. In such
      a compound scheme, which couples a propagative/conservative field dynamics to a
      bistable/dissipative one, we show that by changing the electro-activation voltage
      of the crystal, the CSs can be turned on and shifted with controlled velocity
      across the device section, on the scale of tens of nanoseconds. The configuration
      can be exploited for applications to optical information encoding and processing.

PMID- 23164884
TI  - Single passband microwave photonic filter with wideband tunability and adjustable
      bandwidth.
AB  - A new and simple structure for a single passband microwave photonic filter is
      presented. It is based on using an electro-optical phase modulator and a tunable
      optical filter and only requires a single wavelength source and a single
      photodetector. Experimental results are presented that demonstrate a single
      passband, flat-top radio-frequency filter response without free spectral range
      limitations, along with the capability of tuning the center frequency and filter
      bandwidth independently.

PMID- 23164885
TI  - Distance measurement technique using tilted interference fringe systems and
      receiving optic matching.
AB  - The precise measurement of the distance of fast laterally moving rough surfaces
      is important in several applications such as lathe monitoring. A nonincremental
      interferometer based on two tilted interference fringe systems and a precise
      phase-difference estimation has been realized for this task. However, due to the
      speckle effect, the two scattered light signals exhibit different phase jumps and
      random envelopes causing small correlation coefficients and high uncertainties of
      the phase difference as well as the distance. In this Letter we present for the
      first time a method to enhance the signal correlation coefficient significantly.
      The interference signals are generated by scattered light of a rough surface from
      two different directions. A matching of illumination and receiving optic is
      performed. By this novel method, distance measurements with an uncertainty down
      to 1.2 MUm at about 10 m/s lateral moving velocity have been achieved. Together
      with the simultaneously measured lateral velocity, the shape of rotating objects
      can be precisely determined.

PMID- 23164886
TI  - High dynamic range microscope infrared imaging of silicon nanophotonic devices.
AB  - A noninvasive diagnostic technique based on wavelength-resolved and magnified
      infrared images of weakly scattered light from a silicon photonic device may be
      useful to infer component characteristics, such as waveguide-resonator coupling,
      loss, quality factor, etc., at multiple locations, without the constraint of
      input/output couplers. Here, we demonstrate the benefit of high dynamic range
      microscope imaging for a silicon coupled microresonator device.

PMID- 23164888
TI  - In-plane remote photoluminescence excitation of carbon nanotube by propagating
      surface plasmon.
AB  - In this work, we demonstrate propagating surface plasmon polariton (SPP) coupled
      photoluminescence (PL) excitation of single-walled carbon nanotube (SWNT). SPPs
      were launched at a few micrometers from individually marked SWNT, and plasmon
      coupled PL was recorded to determine the efficiency of this remote in-plane
      addressing scheme. The efficiency depends upon the following factors: (i)
      longitudinal and transverse distances between the SPP launching site and the
      location of the SWNT and (ii) orientation of the SWNT with respect to the plasmon
      propagation wave vector (k(SPP)). Our experiment explores the possible
      integration of carbon nanotubes as a plasmon sensor in plasmonic and nanophotonic
      devices.

PMID- 23164889
TI  - Multichannel optical frequency-locked multicarrier source generation based on
      multichannel recirculation frequency shifter loop.
AB  - We propose and experimentally demonstrate a novel scheme to generate multichannel
      optical frequency-locked multicarrier by using multichannel recirculating
      frequency shifter (MC-RFS) loop. By using MC-RFS loop, we can generate N channels
      subcarriers each round trip without interference. These subcarriers of each
      channel are stable and frequency-locked, which can be used for a multichannel WDM
      source. Finally, the double channels RFS loop is carried out for demonstration in
      our experiment with double-carriers source. Using this scheme, we successfully
      generate 54 frequency-locked subcarriers with 25 GHz frequency spacing in two
      channels and each channel has 27 tones.

PMID- 23164887
TI  - Nonlinear photoacoustic signal increase from endocytosis of gold nanoparticles.
AB  - Nonlinear photoacoustic effects, rarely seen in biomedical photoacoustic imaging
      of tissues, can manifest themselves strongly when plasmonic nanoparticles are
      used as imaging contrast agents. Specifically, nonlinear behavior of
      photoacoustic signal with modest laser fluences can occur when nanoparticles
      undergo cellular endocytosis and aggregation leading to thermal coupling and
      subsequent localized temperature enhancement. Our study demonstrated this effect
      using in vitro tissue models containing cells. While the photoacoustic signal
      amplitude was linearly proportional to the cell/nanoparticle concentration, the
      photoacoustic signal increased nonlinearly as the laser fluence increased. Our
      results, therefore, suggest that the nonlinear effects can be exploited in
      molecular/cellular photoacoustic imaging.

PMID- 23164890
TI  - High-power pulse recirculation in a stable pseudo-confocal geometry.
AB  - A stable pseudo-confocal geometry for recirculation injection by nonlinear gating
      (RING) of high-energy ultrashort pulses is demonstrated. Implementation of RING
      in this robust geometry will benefit the development of ultrabright light sources
      based on inverse Compton scattering by increasing their efficiency. A detailed
      cavity analysis is presented, and a cavity enhancement factor of 17 has been
      experimentally observed.

PMID- 23164891
TI  - Compact acoustic sensor based on air-backed mandrel coiled with optical
      microfiber.
AB  - We propose and demonstrate a compact acoustic sensor comprising a 2 MUm diam, 35
      mm length optical microfiber coiled around a 3 mm diam air-backed mandrel.
      Acoustic waves induce local pressure variations that change the mandrel diameter
      and thus the optical path length of the mode propagating in the microfiber. The
      phase modulation is detected via a single-fiber polarimetric interferometer. The
      low stiffness and minimum bend radii of microfibers gives rise to extremely small
      package sizes without compromising acoustic responsivity.

PMID- 23164892
TI  - Modeling of the optical system illuminated by quasi-monochromatic spatially
      incoherent light: new numerical approach.
AB  - This Letter presents a new method for modeling of complex optical setups
      illuminated by quasi monochromatic spatially incoherent light. The algorithm
      provides better performance and quality than other modeling methods both for
      isoplanatic and nonisoplanatic systems. The algorithm maintains energy relations,
      image orientation, and magnification of the system. Computer modeling and
      experimental results are presented.

PMID- 23164893
TI  - Three-dimensional photonic crystals by large-area membrane stacking.
AB  - We designed and analyzed a "mesh-stack" three-dimensional photonic crystal of a
      12.4% bandgap with a dielectric constant ratio of 12 : 1. The mesh-stack consists
      of four offset identical square-lattice air-hole patterned membranes in each
      vertical period that is equal to the in-plane period of the square lattice. This
      design is fully compatible with the membrane-stacking fabrication method, which
      is based on alignment and stacking of large-area single-crystal membranes
      containing engineered defects. A bandgap greater than 10% is preserved as long as
      the membranes are subjected to in-plane misalignment less than 3% of the square
      period. By introducing a linear defect with a nonsymmorphic symmetry into the
      mesh-stack, we achieved a single-mode waveguide over a wide bandwidth.

PMID- 23164894
TI  - High-finesse cavity external optical feedback DFB laser with hertz relative
      linewidth.
AB  - We report hertz level relative linewidth distributed feedback diode lasers with
      external optical feedback from a high finesse F-P cavity, and demonstrate the
      efficient phase noise suppression and laser linewidth reduction of the optical
      feedback technique. The laser phase noise is dramatically suppressed throughout
      the measurement frequency range. Especially at the Fourier frequency of 17 kHz,
      approximately the linewidth of the F-P reference cavity, the laser phase noise is
      significantly suppressed by more than 92 dB. Above this Fourier frequency, the
      noise maintains a white phase noise plateau as low as -124.4 dBc/Hz. The laser's
      FWHM linewidth is reduced from 7 MHz to 4.4 Hz, and its instantaneous linewidth
      is 220 mHz in the Lorentzian fitting.

PMID- 23164895
TI  - Ultrashort Q-switched pulses from a passively mode-locked distributed Bragg
      reflector semiconductor laser.
AB  - A compact semiconductor mode-locked laser (MLL) is presented that demonstrates
      strong passive Q-switched mode-locking over a wide range of drive conditions. The
      Q-switched frequency is tunable between 1 and 4 GHz for mode-locked pulses widths
      around 3.5 ps. The maximum ratio of peak to average power of the pulse-train is
      >120, greatly exceeding that of similarly sized passively MLLs.

PMID- 23164896
TI  - High-gain wavelength-selective amplification and cavity ring down spectroscopy in
      a fluoride glass erbium-doped microsphere.
AB  - We experimentally demonstrate a compact optical amplifier consisting of a rare
      earth-doped whispering-gallery-mode microsphere coupled via a tapered fiber. A
      gain up to 20 dB is reported in an erbium-doped fluoride glass microsphere 135
      MUm in diameter. Below the amplification regime, the optical gain is used to
      compensate for unavoidable losses due to surface contamination or scattering.
      Quality factor as high as 2*10(9) has been measured by analyzing the transient
      response of the microsphere excited by a dynamically shifted frequency input
      signal.

PMID- 23164897
TI  - Tunable integrated variable bit-rate DPSK silicon receiver.
AB  - We integrate a wavelength-tunable microring resonator with a monolithic Ge-on-Si
      photodetector for use as a variable bit-rate silicon receiver. The integrated
      receiver has a responsivity of 0.7 A/W. We achieved error-free operation for a
      wide range of bit rates from 5 Gb/s to 12.5 Gb/s. The wavelength tuning was
      realized by a TiN-based thermal heater, which enabled tuning of up to ~1 free
      spectral range.

PMID- 23164898
TI  - Third-harmonic spectroscopy and modeling of the nonlinear response of plasmonic
      nanoantennas.
AB  - We perform third-harmonic (TH) spectroscopy on rod-type gold nanoantenna arrays
      using widely tunable sub-30 fs laser pulses. We find the peak of the TH
      generation efficiency of the antenna arrays always slightly redshifted with
      respect to the peak of their linear extinction spectrum. We model the wavelength
      dependent TH response quantitatively using a nonlinear harmonic oscillator model.

PMID- 23164899
TI  - Highly selective two-color mid-wave and long-wave infrared detector hybrid based
      on Type-II superlattices.
AB  - We report a two-color mid-wave infrared (MWIR) and long-wave infrared (LWIR) co
      located detector with 3 MUm active region thickness per channel that is highly
      selective and can perform under high operating temperatures for the MWIR band.
      Under back-side illumination, a temperature evolution study of the MWIR
      detector's electro-optical performance found the 300 K background-limit with 2pi
      field-of-view to be achieved below operating temperatures of 160 K, at which the
      temperature's 50% cutoff wavelength was 5.2 MUm. The measured current reached the
      system limit of 0.1 pA at 110 K for 30 MUm pixel-sized diodes. At 77 K, where the
      LWIR channel operated with a 50% cutoff wavelength at 11.2 MUm, an LWIR
      selectivity of ~17% was achieved in the MWIR wave band between 3 and 4.7 MUm,
      making the detector highly selective.

PMID- 23164900
TI  - Embedded coupler based on selectively infiltrated photonic crystal fiber for
      strain measurement.
AB  - A photonic crystal fiber (PCF) with embedded coupler is demonstrated for strain
      measurement. The embedded coupler is constructed by the selective filling of one
      of the air holes in the PCF. Light propagated in the fiber core can be
      efficiently coupled to the liquid-filled rod waveguide under phase-matching
      conditions, resulting in sharp decreasing of resonant wavelength intensity. The
      highest strain sensitivity is calculated to be ~23.8 pm/MUepsilon due to the
      coupling between core mode and fundamental mode of the liquid rod, when the
      refractive index (RI) of the liquid is 1.46. With the increase of the RI, the
      resonance can also be observed between the core mode and the higher-order modes
      of the liquid rod, whereas the strain sensitivity drops to ~6.4 pm/MUepsilon. The
      experimentally obtained static strain sensitivity values are ~22 and ~3.8
      pm/MUepsilon for the coupling between the core mode and the fundamental mode or
      linearly polarized LP(11) modes of the liquid rod, respectively, which are in
      good agreement with the simulations. The dynamic strain measurement resolution
      obtained is ~1.2 nepsilon/(Hz)(1/2).

PMID- 23164901
TI  - Passively mode-locked Yb3+:Sc2SiO5 thin-disk laser.
AB  - Experimental investigations on a passively mode-locked Yb(3+):Sc(2)SiO(5)
      (Yb:SSO) thin-disk laser are presented. The mode-locking was performed with a
      commercially available semiconductor saturable absorber mirror. The laser was
      operated at a repetition rate of 27 MHz and generated a maximum average output
      power of 27.8 W with a pulse duration of 298 fs. The spectrum was centered at
      1036 nm. The beam was measured to be close to diffraction limited (M(2)<1.1). The
      promising results confirm the suitability of Yb:SSO for mode-locked thin-disk
      laser oscillators and indicate that this comparably new material deserves further
      attention by optimizing the crystal quality (growth and polishing) and doping
      levels for further power scaling.

PMID- 23164902
TI  - 2 Tbit/s free-space data transmission on two orthogonal orbital-angular-momentum
      beams each carrying 25 WDM channels.
AB  - We demonstrate a 2 Tbit/s free-space data link using two orthogonal orbital
      angular momentum beams each carrying 25 different wavelength-division
      multiplexing channels. We measure the performance for different modulation
      formats, including directly detected 40 Gbit/s nonreturn-to-zero (NRZ)
      differential phase-shift keying, 40 Gbit/s NRZ on-off keying, and coherently
      detected 10 Gbaud NRZ quadrature phase-shift keying, and achieve low bit error
      rates with penalties less than 5 dB.

PMID- 23164903
TI  - Whispering gallery mode laser based on antitumor drug-dye complex gain medium.
AB  - Optofluidic lasers have emerged as a new research field over the past few years.
      Most frequently they use conventional dye molecules as the gain medium. In this
      Letter, we demonstrate a laser emission produced by the coupling of the
      evanescent whispering gallery modes that resonate in a cylindrical microresonator
      to a newly developed gain medium. This medium is formed by attachment of a 7
      nitrobenzo [c] [1,2,5]-oxadiazol-4-yl fluorescent tag to tamoxifen, the most
      widely used drug in the treatment of breast cancer. The antitumor character of
      the gain medium paves the way to novel biophotonic applications.

PMID- 23164904
TI  - Multicorelike guidance in a triangular-core hollow optical fiber and spectral
      evolution of its eigenmode degeneracy.
AB  - A unique multicorelike guidance was achieved in a microstructured optical fiber
      composed of a circular air hole at the center surrounded by a high-index
      triangular core. Unique spectral evolution of the degeneracy was theoretically
      investigated using a vectorial finite element method to find a threefold
      degeneracy in both the fundamental and the first excited modes in the visible
      range, which evolved to twofold degeneracy as the wavelength increased to IR.
      Experimental measurements also confirmed evolution of the modal intensity from
      three spatially isolated patterns confined to individual corners into a supermode
      combining the three corners.

PMID- 23164905
TI  - Terahertz tuning of whispering gallery modes in a PDMS stand-alone, stretchable
      microsphere.
AB  - We report on tuning the optical whispering gallery modes (WGMs) in a poly
      dimethyl siloxane-based (PDMS) microsphere resonator by more than 1 THz. The PDMS
      microsphere system consists of a solid spherical resonator directly formed with
      double stems on either side. The stems act like tie-rods for simple mechanical
      stretching of the microresonator, resulting in tuning of the WGMs by one free
      spectral range. Further investigations demonstrate that the WGM shift has a
      higher sensitivity (0.13 nm/MUN) to an applied force when the resonator is in its
      maximally stretched state compared to its relaxed state.

PMID- 23164906
TI  - Spectral characteristics of quantum-cascade laser operating at 10.6 MUm
      wavelength for a seed application in laser-produced-plasma extreme UV source.
AB  - In this Letter, we investigate, for the first time to our knowledge, the spectral
      properties of a quantum-cascade laser (QCL) from a point of view of a new
      application as a laser seeder for a nanosecond-pulse high-repetition frequency
      CO(2) laser operating at 10.6 MUm wavelength. The motivation for this work is a
      renewed interest in such a pulse format and wavelength driven by a development of
      extreme UV (EUV) laser-produced-plasma (LPP) sources. These sources use pulsed
      multikilowatt CO(2) lasers to drive the EUV-emitting plasmas. Basic spectral
      performance characteristics of a custom-made QCL chip are measured, such as
      tuning range and chirp rate. The QCL is shown to have all essential qualities of
      a robust seed source for a high-repetition nanosecond-pulsed CO(2) laser required
      by EUV LPP sources.

PMID- 23164907
TI  - Acoustic vibration sensor based on nonadiabatic tapered fibers.
AB  - A simple and low-cost vibration sensor based on single-mode nonadiabatic fiber
      tapers is proposed and demonstrated. The environmental vibrations can be detected
      by demodulating the transmission loss of the nonadiabatic fiber taper.
      Theoretical simulations show that the transmission loss is related to the
      microbending of the fiber taper induced by vibrations. Unlike interferometric
      sensors, this vibration sensor does not need any feedback loop to control the
      quadrature point to obtain a stable performance. In addition, it has no
      requirement for the coherence of the light source and is insensitive to
      temperature changes. Experimental results show that this sensing system has a
      wide frequency response range from a few hertz to tens of kilohertz with the
      maximal signal to noise ratio up to 73 dB.

PMID- 23164908
TI  - Surface passivation dependent photoluminescence from silicon quantum dot
      phosphors.
AB  - We demonstrate wavelength-tunable, air-stable and nontoxic phosphor materials
      based on silicon quantum dots (SiQDs). The phosphors, which are composed of
      micrometer-size silicon particles with attached SiQDs, are synthesized by an
      electrochemical etching method under ambient conditions. The photoluminescence
      (PL) peak wavelength can be controlled by the SiQD size due to quantum
      confinement effect, as well as the surface passivation chemistry of SiQDs. The
      red-emitting phosphors have PL quantum yield equal to 17%. The SiQD-phosphors can
      be embedded in polymers and efficiently excited by 405 nm light-emitting diodes
      for potential general lighting applications.

PMID- 23164909
TI  - Virtual source for an Airy beam.
AB  - We identify a virtual source for generating an Airy wave. A spectral integral
      expression is derived to describe the Airy wave, which, in the paraxial limit,
      yields the freely accelerating, nondiffracting, and finite energy Airy beam. From
      the spectral representation of the Airy wave, the first two orders of nonparaxial
      corrections to the paraxial Airy beam are determined. Also, a connection between
      the obtained Airy wave and the well-known complex source point spherical wave is
      given.

PMID- 23164910
TI  - Pulse dynamics of dissipative soliton resonance with large duration-tuning range
      in a fiber ring laser.
AB  - The pulse dynamics operating in dissipative soliton resonance (DSR) region is
      experimentally investigated in a fiber ring laser. With the increase of pump
      power, the pulse profile transit from sech-like to rectangular shape was
      observed. The generated pulse in DSR region exhibits the conventional soliton
      spectrum with sideband generation. The duration-tuning range of the rectangular
      pulse is up to the cavity roundtrip time. Particularly, during the process of
      pulse duration broadening it was found that the rectangular pulse would trap a
      weak pulse generated from cw background. The obtained results may be useful for
      better understanding the DSR phenomenon.

PMID- 23164911
TI  - Physical-optics approximation of near-critical-angle scattering by spheroidal
      bubbles.
AB  - A first-order approximation is derived for the near-critical-angle scattering of
      a large spheroidal bubble illuminated by a plane wave propagating along the
      bubble axis of symmetry. The intensity of the far-field scattering pattern is
      expressed as a function of the relative refractive index and the two radii of
      curvature of the spheroidal bubble at the critical impact point.

PMID- 23164912
TI  - Direct Monte Carlo computation of time-resolved fluorescence in heterogeneous
      turbid media.
AB  - We show that a multiexponential model for time-resolved fluorescence allows the
      use of an absorption-perturbation Monte Carlo (MC) approach based on stored
      photon path histories. This enables the rapid fitting of fluorescence yield,
      lifetimes, and background tissue absorptions in complex heterogeneous media
      within a few seconds, without the need for temporal convolutions or MC
      recalculation of photon path lengths. We validate this method using simulations
      with both a slab and a heterogeneous model of the mouse head.

PMID- 23164913
TI  - Lens equation for flat lenses made with hyperbolic metamaterials.
AB  - This study aims to give a general theory that enables the design of flat lenses
      based on hyperbolic metamaterials. We derive a lens equation that is demonstrated
      to involve the curvature of the dispersion relation. Guided by this theory,
      hyperbolic lenses of focal length ranging from zero to a few wavelength are
      simulated. High transmission efficiency is also obtained by reducing the amount
      of metal compared to the dielectric material.

PMID- 23164914
TI  - Phenomenon in an alcohol not full-filled temperature sensor based on an optical
      fiber Sagnac interferometer.
AB  - An alcohol not full-filled high-birefringence photonic crystal fiber (HiBi-PCF)
      temperature sensor based on an optical fiber Sagnac interferometer (OFSI) is
      demonstrated and investigated in detail. A new phenomenon that the resonant dip
      wavelengths of the temperature sensor blueshift with temperature increasing is
      observed, which is contrary to that of the previously reported alcohol filled
      HiBi-PCF OFSI temperature sensor. By considering the influences of the group
      birefringence and the thermo expansion of alcohol, this phenomenon is explained
      very well. The temperature sensitivity of the proposed sensor is about -1.17 nm/
      degrees C and is only one-sixth of that of the alcohol full-filled HiBi-PCF OSFI.

PMID- 23164915
TI  - Phase conjugation based on single backward second-order nonlinear parametric
      process.
AB  - We show that backward difference-frequency generation can be exploited to achieve
      phase conjugation in a second-order nonlinear medium. The backward configuration
      can be utilized to achieve broadband quasi-phase-matching, compared with the
      forward counterpart. Our calculation shows that a nonlinear reflectivity of close
      to 100% is achievable from a laser emitting an output power of ~1 mW. Such an
      efficient phase conjugator is made feasible by placing the nonlinear medium
      inside a pump laser cavity. In addition, a Fabry-Perot resonator at the input
      frequency is used to significantly improve the nonlinear reflectivity.

PMID- 23164917
TI  - Stimulated-Brillouin-scattering-suppressed high-power single-frequency
      polarization-maintaining Raman fiber amplifier with longitudinally varied strain
      for laser guide star.
AB  - An up to 44 W, 1 MHz linewidth, 1178 nm CW laser is obtained by Raman
      amplification of a distributed feedback diode laser in a variably strained
      polarization-maintaining fiber with a record-high optical efficiency of 52%,
      pumped by a linearly polarized 1120 nm fiber laser. A polarization extinction
      ratio of 30 dB is achieved due to the all-polarization-maintaining configuration
      and the polarization dependence of Raman gain. The strain distribution is
      designed according to the signal power evolution along the fiber. A 20 times
      reduction in the effective stimulated Brillouin scattering coefficient is
      achieved. A 24.3 W 589 nm laser is generated by an external resonant doubling
      cavity with an optical efficiency of 68.5%. The laser is locked to 589.1591 nm
      for a laser guide star.

PMID- 23164918
TI  - Stokes vector characterization of the polarization behavior of vertical-cavity
      surface-emitting lasers.
AB  - We demonstrate that a full polarization analysis in terms of the Stokes vector
      parameters is necessary to determine the polarization state of light emitted by
      vertical-cavity surface-emitting lasers (VCSELs). For three selected
      representative VCSEL devices, we measured the injection current dependence of the
      three Stokes parameters and compared these results with linearly selected
      polarization P-I curves, clearly demonstrating that a complete polarization
      analysis is required to unveil the full polarization behavior.

PMID- 23164919
TI  - Subpixel smoothing finite-difference time-domain method for material interface
      between dielectric and dispersive media.
AB  - In this Letter, we have shown that the subpixel smoothing technique that
      eliminates the staircasing error in the finite-difference time-domain method can
      be extended to material interface between dielectric and dispersive media by
      local coordinate rotation. First, we show our method is equivalent to the
      subpixel smoothing method for dielectric interface, then we extend it to a more
      general case where dispersive/dielectric interface is present. Finally, we
      provide a numerical example on a scattering problem to demonstrate that we were
      able to significantly improve the accuracy.

PMID- 23164920
TI  - Generation of carrier-envelope phase-stable two optical-cycle pulses at 2 MUm
      from a noncollinear beta-barium borate optical parametric amplifier.
AB  - We report on the generation of two optical-cycle, carrier-envelope phase-stable
      pulses with energy of 15 MUJ at central wavelength of 2 MUm. Pulses of 15 fs (2.3
      optical cycles) duration are obtained by difference-frequency generation, which
      at the same time provides passive carrier-envelope phase stabilization, and
      noncollinear optical parametric amplification in beta-barium borate crystal,
      which is shown to provide broad phase-matching bandwidth if seeded by pulses in
      the 1.6-2.6 MUm wavelength range. Pulse compression is achieved by means of a
      simple propagation through the optical setup and by precisely controlling the
      initial chirp of the pulses to be frequency downconverted.

PMID- 23164921
TI  - Catalpol inhibits LPS plus IFN-gamma-induced inflammatory response in astrocytes
      primary cultures.
AB  - A large body of evidence suggests that the inflammatory reaction plays an
      important role in the pathogenesis of neurodegenerative diseases. Our previous
      studies described the neuroprotective effects of catalpol in lipopolysaccharide
      (LPS)-induced inflammatory models, in which catalpol was shown to prevent
      mesencephalic neuron death and ameliorate cognitive ability animals. To further
      investigate the protective effect and underlying mechanism of catalpol,
      astrocytes were pretreated with low (0.1mM) and high dose (0.5mM) catalpol for 1h
      prior to LPS plus interferon-gamma stimulation. Biochemical analyses showed that
      NO and ROS production and iNOS activity were significantly reduced by catalpol.
      Data at transcriptional level also demonstrated that catalpol potently attenuated
      gene expressions involved in inflammation, such as iNOS, COX-2 and TLR4. In
      addition, our exploration further revealed that the suppressive action of
      catalpol on inflammation was mediated via inhibiting nuclear factor-kappaB (NF
      kappaB) activation. Collectively, these results suggest that catalpol can exert
      inhibitory effects on the inflammatory reaction in astrocytes and that
      inactivation of NF-kappaB could be the major determinant for its anti
      inflammatory mechanism. Therefore, catalpol may potentially be a highly effective
      therapeutic agent in treating neurodegenerative diseases associated with
      inflammation.

PMID- 23164922
TI  - Alveolar corticotomy: a new surgical approach based on bone activation: principle
      and protocol.
AB  - Alveolar corticotomy has proven effective in shortening orthodontic treatments in
      adults. A new non-invasive and flapless surgical approach has, however, yielded
      the same results. This technique, based on prior osteogenic alveoli preparation,
      entails neither anatomical risk nor post-op pain. The present article describes
      this new protocol and uses a case report to illustrate it.

PMID- 23164924
TI  - Development of an oral assessment tool to evaluate appetite in patients with head
      and neck cancer receiving radiotherapy.
AB  - PURPOSE: The objective of this study was to develop an oral assessment tool for
      evaluating the appetite of patients with head and neck cancer receiving
      radiotherapy, who had dysgeusia, xerostomia, and oral mucositis, as well as to
      verify its validity and reliability. METHODS AND SAMPLE: A draft oral assessment
      tool, which included a 5-point scale and 19 items, was prepared based on an
      interview survey of 30 patients. The resultant questionnaire survey was provided
      to 209 subjects. RESULTS: On the basis of factor analysis of construct validity,
      3 factors (dysgeusia and loss of favors), (salivation abnormality and loss of
      moisture in the oral cavity), and (pain in the oral cavity and lack of
      motivation) comprising 14 items were adopted for the final survey. During a
      review of criteria validity, a correlation was found between the scores of the
      three factors and overall oral assessment tool, and the scores of taste
      sensitivity, xerostomia, oral mucositis, and appetite with a correlation
      coefficient of r = 0.41-0.89 (p < 0.01). With regard to reliability, stability
      was determined as 0.87 (p < 0.01) according to test-retest study results.
      Internal consistency was confirmed by a Cronbach's alpha coefficient of 0.83 (p <
      0.01) and an interclass correlation coefficient of 0.80 (p < 0.01). CONCLUSIONS:
      On the basis of the validity and reliability of the oral assessment tool
      developed, it has been found to be practical for use in the assessment of
      appetite of patients with head and neck cancer.

PMID- 23164925
TI  - Provision of cancer information as a "support for navigating the knowledge
      landscape": findings from a critical interpretive literature synthesis.
AB  - PURPOSE OF THE RESEARCH: Information is often seen as a crucial tool for the
      support of cancer patients, facilitating their involvement in care management and
      in decision-making. The importance of theory in guiding provision of cancer
      information has been widely accepted, but there is a growing need for critical
      reflection on the concepts underlying approaches to information provision. This
      paper presents findings from a critical review of literature related to
      information in cancer care. METHODS: Critical interpretive synthesis (CIS) was
      employed to review and synthesise published literature. 57 publications were
      selected in a multi-step systematic process. Their content was analysed and
      synthesised using established methodology consistent with primary qualitative
      research. KEY RESULTS: The synthesis identified and characterised a concept of
      cancer information provision as a "support for navigating the knowledge
      landscape". This concept recognises the diverse, changing and relational nature
      of patients' values, needs and preferences. It promotes a view of information
      provision as an ongoing and flexible process of navigating different resources,
      which in turn support the navigation of patients' broader experiences of their
      health and care. This process recognises various levels of patient involvement
      with healthcare services, and ensures timely provision of selected and personally
      relevant information. CONCLUSION: The concept of "support for navigating the
      knowledge landscape" offers a useful way of envisaging information services for
      people with cancer (and possibly also with other chronic illnesses), which would
      be responsive to patients' needs and preferences.

PMID- 23164926
TI  - Fabrication of platinum-decorated single-walled carbon nanotube based hydrogen
      sensors by aerosol jet printing.
AB  - The coffee ring effect is reduced effectively and a hydrogen sensor with platinum
      decorated single-walled carbon nanotubes (SWCNTs) is prepared by aerosol jet
      printing (AJP) technology. The stable aqueous solution of platinum functional
      SWCNTs is prepared by a series of chemical and physical processes and the
      electrode array is formed by micro-fabrication technology. The AJP process is
      also researched in detail including the number of printing passes and the
      printing distance between electrodes. Then, the functional SWCNT aqueous solution
      is printed on the electrode array and the response of this sensor to the hydrogen
      is measured carefully.  The results show that a functional SWCNT sensor has
      excellent sensing properties toward hydrogen.

PMID- 23164927
TI  - Kinetics of protein unfolding at interfaces.
AB  - The conformation of protein molecules is determined by a balance of various
      forces, including van der Waals attraction, electrostatic interaction, hydrogen
      bonding, and conformational entropy. When protein molecules encounter an
      interface, they are often adsorbed on the interface. The conformation of an
      adsorbed protein molecule strongly depends on the interaction between the protein
      and the interface. Recent time-resolved investigations have revealed that protein
      conformation changes during the adsorption process due to the protein-protein
      interaction increasing with increasing interface coverage. External conditions
      also affect the protein conformation. This review considers recent dynamic
      observations of protein adsorption at various interfaces and their implications
      for the kinetics of protein unfolding at interfaces.

PMID- 23164928
TI  - Synthesis of borasiloxane-based macrocycles by multicomponent condensation
      reactions in solution or in a ball mill.
AB  - Large macrocycles containing imine and borasiloxane links are obtained in
      polycondensation reactions of 4-formylbenzeneboronic acid, t-Bu(2)Si(OH)(2), and
      diamines. The multicomponent reactions can be performed in solution or-
      advantageously--by mechanochemical syntheses in a ball mill.

PMID- 23164929
TI  - Measurement of systemic oxygen delivery and inotropy in healthy term neonates
      with the Ultrasonic Cardiac Output Monitor (USCOM).
AB  - INTRODUCTION: The aim of this study was to assess the normal values for Smith
      Madigan inotropy (SMI), Smith-Madigan inotropy index (SMII), oxygen delivery
      (DO2) and oxygen delivery index DO2I in healthy term neonates on the first day of
      life and during circulatory adaptation over the first three days of life.
      METHODS: Hemodynamics of the left heart were measured non-invasively in 71 normal
      full-term neonates over the first three days using the Ultrasonic Cardiac Output
      Monitor (USCOM). This was combined with hemoglobin concentration from umbilical
      cord blood and pulse oximetry to calculate DO2 and DO2I. Blood pressure was
      measured using automated oscillometry and combined with the hemodynamic measures
      and hemoglobin concentration using the Smith-Madigan method to calculate inotropy
      (SMI) and inotropy index (SMII). RESULTS: SMI and SMII showed no significant
      change during the study period, ranging from 154 to 168 mW and 694 to 731
      mW/m(2). Mean (SD) DO2 and DO2I showed a significant fall over three days from
      131 (63) ml/min and 596 (278) ml/m(2)/min to 118 (46) ml/min and 517 (173)
      ml/m(2)/min (p<0.01 and <0.001 respectively) with a corresponding decrease in
      cardiac output from 758 (143) ml/min to 658 (131) ml/min, (p=0.002). There was no
      significant change in stroke volume, heart rate, SMI or SMII within the first
      day. DO2 and DO2I showed small but significant decreases within the first day
      from 153 (46) ml/min and 699 (174) ml/min/m(2) to 129 (36) ml/min and 609 (141)
      ml/min/m(2) (p=0.017 and 0.048 respectively). CONCLUSIONS: Normal inotropy of the
      left heart and systemic DO2 values in healthy full-term neonates over the first
      three days of life were assessed using the USCOM. Subjects showed stable
      myocardial contractility over the first three days with decreasing DO2 and DO2I
      in line with the decrease in cardiac output (CO). DO2 and DO2I showed small but
      significant reductions during the first 24 h. USCOM proved to be a feasible and
      convenient non-invasive bedside tool to assess inotropy and oxygen delivery in
      neonates.

PMID- 23164930
TI  - c-Fos immunoreactivity in the pig brain following deoxynivalenol intoxication:
      focus on NUCB2/nesfatin-1 expressing neurons.
AB  - Deoxynivalenol (DON), produced by the cereal-contaminating Fusarium fungi, is a
      major trichothecene responsible for mycotoxicoses in farm animals, including
      swine. The main effect of DON-intoxication is food intake reduction and the
      consequent body weight loss. The present study aimed to identify brain structures
      activated during DON intoxication in pigs. To this goal, we used c-Fos staining
      which constitutes a useful approach to identify activated neurons. We showed that
      per os administration of Fusarium graminearum extracts (containing the equivalent
      of 1mg DON per kg of body weight) induced an increase in c-Fos immunoreactivity
      in several central structures, including the ventrolateral medulla (VLM), dorsal
      vagal complex (DVC), paraventricular nucleus of the hypothalamus (PVN), arcuate
      nucleus (Arc), supraoptic nucleus (SON) and amygdala (CeA). Moreover, we coupled
      c-Fos staining with phenotypic markers detection in order to specify the neuronal
      populations activated during DON intoxication. This phenotypic characterization
      revealed the activation of catecholaminergic but not of serotoninergic neurons in
      response to the toxin. In this context, we also paid a particular attention to
      NUCB2/nesfatin-1 positive cells, since nesfatin-1 is known to exert a satiety
      effect. We report here, for the first time in the pig brain, the presence of
      NUCB2/nesfatin-1 neurons in the VLM, DVC, PVN, Arc and SON, and their activation
      during DON intoxication. Taken together, these data show that DON stimulates the
      main structures involved in food intake in pigs and suggest that
      catecholaminergic and NUCB2/nesfatin-1 neurons could contribute in the
      anorexigenic effects of the mycotoxin.

PMID- 23164931
TI  - The perirhinal cortex of rats: an intricate area for microinfusion of
      anticonvulsants against soman-induced seizures.
AB  - Microinfusion of anticonvulsants into the perirhinal cortex through 1 guide
      cannula in each hemisphere only invades a small area of this seizure controlling
      site in rats exposed to soman. The purpose of the present study was to examine
      whether infusions made through 2 cannulas in each perirhinal cortex may produce
      more efficacious anticonvulsant action against soman intoxication than the use of
      1 cannula only in rats infused with the ionotropic antagonists procyclidine and
      caramiphen or the metabotropic glutamate modulators DCG-IV and MPEP. The results
      showed that the mere presence of indwelling double cannulas caused proconvulsant
      effect in response to subsequent systemic administration of soman. Both the
      control and caramiphen groups with double cannulas had significantly shorter
      latencies to seizure onset than the corresponding groups with single cannula.
      Procyclidine resulted in anticonvulsant efficacy, even in rats with double
      cannulas. In rats that received twin infusions of DCG-IV or MPEP, the
      anticonvulsant impact was very high, inasmuch as a majority of the rats in each
      group was protected against seizure activity. Drugs possessing powerful
      anticonvulsant potency can apparently counteract the proconvulsant effect of
      double cannulas, and some can even gain enhanced anticonvulsant capacity when
      invading a larger area of the perirhinal cortex. Perirhinal EEG recordings
      (electrodes in indwelling cannulas) in a separate set of rats not exposed to
      soman or drugs showed no differences in basal electrical activity (total power
      0.5-25Hz or the theta band 4-12Hz) between groups with single or double cannulas.
      The intrinsic excitability and synaptic connectivity of the perirhinal cortex may
      be associated with the proconvulsant impact observed in rats with double cannulas
      when exposed to soman.

PMID- 23164932
TI  - Korean red ginseng ameliorates acute 3-nitropropionic acid-induced cochlear
      damage in mice.
AB  - 3-Nitropropionic acid (3-NP), a mitochondrial toxin, has been reported to induce
      an acute cochlear damage. Korean red ginseng (KRG) is known to have protective
      effects from some types of hearing loss. This study aimed to observe the
      protective effect of KRG in an ototoxic animal model using 3-NP intratympanic
      injection. BALB/c mice were classified into 5 groups (n=15) and dose-dependent
      toxic effects after intratympanic injection with 3-NP (300-5000 mM) on the left
      ear were investigated to determine the appropriate toxicity level of 3-NP. For
      observation of the protective effects of KRG, 23 mice were grouped into 3-NP (500
      mM, n=12) and KRG+3-NP groups (300 mg/kg KRG for 7 days before 500 mM 3-NP
      administration, n=11). Auditory brain response (ABR) and cochlear morphological
      evaluations were performed before and after drug administration. The ABR
      thresholds in the 800-5000 mM groups exceeded the maximum recording limit at 16
      and 32 kHz 1 day after 3-NP administration. The ABR threshold in the 500 mM 3
      NP+KRG group was significantly lower than that in the 500 mM 3-NP group from post
      1 week to 1 month. The mean type II fibrocyte counts significantly differed
      between the control and 3-NP groups and between the 3-NP and 3-NP+KRG groups.
      Spiral ganglion cell degeneration in the 3-NP group was more severe than that in
      the 3-NP+KRG group. This animal model exhibited a dose-dependent hearing loss
      with histological changes. KRG administration ameliorated the deterioration of
      hearing by 3-NP.

PMID- 23164933
TI  - Proteomic and functional analyses of protein-DNA complexes during gene transfer.
AB  - One of the barriers to successful nonviral gene delivery is the crowded
      cytoplasm, which plasmids need to actively traverse for gene expression.
      Relatively little is known about how this process occurs, but our lab and others
      have shown that the microtubule network and motors are required for plasmid
      movement to the nucleus. To further investigate how plasmids exploit normal
      physiological processes to transfect cells, we have taken a proteomics approach
      to identify the proteins that comprise the plasmid-trafficking complex. We have
      developed a live cell DNA-protein pull-down assay to isolate complexes at certain
      time points post-transfection (15 minutes to 4 hours) for analysis by mass
      spectrometry (MS). Plasmids containing promoter sequences bound hundreds of
      unique proteins as early as 15 minutes post-electroporation, while a plasmid
      lacking any eukaryotic sequences failed to bind many of the proteins. Specific
      proteins included microtubule-based motor proteins (e.g., kinesin and dynein),
      proteins involved in protein nuclear import (e.g., importin 1, 2, 4, and 7, Crm1,
      RAN, and several RAN-binding proteins), a number of heterogeneous nuclear
      ribonucleoprotein (hnRNP)- and mRNA-binding proteins, and transcription factors.
      The significance of several of the proteins involved in protein nuclear
      localization and plasmid trafficking was determined by monitoring movement of
      microinjected fluorescently labeled plasmids via live cell particle tracking in
      cells following protein knockdown by small-interfering RNA (siRNA) or through the
      use of specific inhibitors. While importin beta1 was required for plasmid
      trafficking and subsequent nuclear import, importin alpha1 played no role in
      microtubule trafficking but was required for optimal plasmid nuclear import.
      Surprisingly, the nuclear export protein Crm1 also was found to complex with the
      transfected plasmids and was necessary for plasmid trafficking along microtubules
      and nuclear import. Our results show that various proteins involved in nuclear
      import and export influence intracellular trafficking of plasmids and subsequent
      nuclear accumulation.

PMID- 23164934
TI  - Targeting gonadotropin-releasing hormone receptor inhibits the early step of
      ovarian cancer metastasis by modulating tumor-mesothelial adhesion.
AB  - Ovarian cancer has a clear predilection to metastasize to the peritoneum, which
      represents one of the most important prognostic factors of poor clinical outcome.
      Gonadotropin-releasing hormone (GnRH) receptor is significantly overexpressed
      during the malignant progression of human ovarian cancer. Here, using lentiviral
      based small interfering RNA (siRNA) technology to downregulate GnRH receptor in
      metastatic ovarian cancer cells, we show that GnRH receptor is an important
      mediator of ovarian cancer peritoneal metastasis. GnRH receptor downregulation
      dramatically attenuated their adhesion to the peritoneal mesothelium. By
      inhibiting the expression of GnRH receptor, we showed decreased expression of
      alpha2beta1 and alpha5beta1 integrin and adhesion to specific extracellular
      matrix (ECM) proteins. This was also associated with a reduction of P-cadherin.
      Furthermore, adhesion of ovarian cancer cells to different ECMs and the
      mesothelium were abrogated in response to beta1 integrin and P-cadherin
      reduction, confirming that the effects were beta1 integrin- and P-cadherin
      specific. Using a mouse model of human ovarian cancer metastasis, we found that
      the inhibition of GnRH receptor, beta1 integrin, and P-cadherin significantly
      attenuated tumor growth, ascites formation, and the number of metastatic
      implants. These results define a new role for GnRH receptor in early metastasis
      and offer the possibility of novel therapeutic targets.

PMID- 23164935
TI  - Functional in vivo delivery of multiplexed anti-HIV-1 siRNAs via a chemically
      synthesized aptamer with a sticky bridge.
AB  - One of the most formidable impediments to clinical translation of RNA
      interference (RNAi) is safe and effective delivery of the siRNAs to the desired
      target tissue at therapeutic doses. We previously described in vivo cell type
      specific delivery of anti-HIV small-interfering RNAs (siRNAs) through covalent
      conjugation to an anti-gp120 aptamer. In order to improve the utility of aptamers
      as siRNA delivery vehicles, we chemically synthesized the gp120 aptamer with a 3'
      7-carbon linker (7C3), which in turn is attached to a 16-nucleotide 2' OMe/2' Fl
      GC-rich bridge sequence. This bridge facilitates the noncovalent binding and
      interchange of various siRNAs with the same aptamer. We show here that this
      aptamer-bridge-construct complexed with three different Dicer substrate siRNAs
      (DsiRNAs) results in effective delivery of the cocktail of DsiRNAs in vivo,
      resulting in knockdown of target mRNAs and potent inhibition of HIV-1
      replication. Following cessation of the aptamer-siRNA cocktail treatment, HIV
      levels rebounded facilitating a follow-up treatment with the aptamer cocktail of
      DsiRNAs. This follow-up injection resulted in complete suppression of HIV-1 viral
      loads that extended several weeks beyond the final injection. Collectively, these
      data demonstrate a facile, targeted approach for combinatorial delivery of
      antiviral and host DsiRNAs for HIV-1 therapy in vivo.

PMID- 23164936
TI  - Adipose-derived stromal cells overexpressing vascular endothelial growth factor
      accelerate mouse excisional wound healing.
AB  - Angiogenesis is essential to wound repair, and vascular endothelial growth factor
      (VEGF) is a potent factor to stimulate angiogenesis. Here, we examine the
      potential of VEGF-overexpressing adipose-derived stromal cells (ASCs) for
      accelerating wound healing using nonviral, biodegradable polymeric vectors. Mouse
      ASCs were transfected with DNA plasmid encoding VEGF or green fluorescent protein
      (GFP) using biodegradable poly (beta-amino) esters (PBAE). Cells transfected
      using Lipofectamine 2000, a commercially available transfection reagent, were
      included as controls. ASCs transfected using PBAEs showed enhanced transfection
      efficiency and 12-15-fold higher VEGF production compared with cells transfected
      using Lipofectamine 2000 (*P < 0.05). When transplanted into a mouse wild-type
      excisional wound model, VEGF-overexpressing ASCs led to significantly accelerated
      wound healing, with full wound closure observed at 8 days compared to 10-12 days
      in groups treated with ASCs alone or saline control (*P < 0.05). Histology and
      polarized microscopy showed increased collagen deposition and more mature
      collagen fibers in the dermis of wound beds treated using PBAE/VEGF-modified ASCs
      than ASCs alone. Our results demonstrate the efficacy of using nonviral
      engineered ASCs to accelerate wound healing, which may provide an alternative
      therapy for treating many diseases in which wound healing is impaired.

PMID- 23164937
TI  - Particle tracking analysis for the intracellular trafficking of nanoparticles
      modified with African swine fever virus protein p54-derived peptide.
AB  - Previous studies showed that the cytoplasmic transport of nanoparticles to the
      nucleus is driven by a vesicular sorting system. Artificial approaches for
      targeting a microtubule-associating motor complex is also a challenge. We
      describe herein the development of a liposomal nanoparticle, the surface of which
      is modified with stearylated octa-arginine (STR-R8), and a dynein light chain
      (LC8)-associated peptide derived from an African swine fever virus protein p54
      (p54(149-161)) with polyethyleneglycol (PEG) as a spacer (p54(149-161)-PEG/R8
      liposomal nanoparticles (LNPs)). The p54(149-161)-PEG/R8-LNPs preferentially gain
      access to the nucleus, resulting in a one- to two-order of magnitude higher
      transfection activity in comparison with p54(149-161)-free nanoparticles (PEG/R8
      LNPs). Further studies of particle tracking in HeLa cells stably expressing green
      fluorescent protein (GFP)-tagged tubulin (GFP/Tub-HeLa) indicate that p54(149
      161) stimulated the transport of nanoparticles along fibrous tubulin structures.
      Moreover, a part of the p54(149-161)-PEG/R8-LNPs appeared to undergo quasi
      straight transport without sharing the tracks corresponding to PKH67, the plasma
      membrane of which had been prestained with a marker just before transfection,
      while corresponding movement was never observed in the case of PEG/R8-LNPs. These
      findings suggest that a portion of the p54(149-161)-modified nanoparticles can
      use microtubule-dependent transport without the need for an assist by a vesicular
      sorting system.

PMID- 23164938
TI  - Polyethylenimine-modified pluronics (PCMs) improve morpholino oligomer delivery
      in cell culture and dystrophic mdx mice.
AB  - We investigated a series of small-sized polyethylenimine (PEI, 0.8/1.2 k)
      conjugated pluronic copolymers (PCMs) for their potential to enhance delivery of
      an antisense phosphorodiamidate morpholino oligomer (PMO) in vitro and in
      dystrophic mdx mice. PCM polymers containing pluronics of molecular weight (Mw)
      ranging 2-6 k, with hydrophilic-lipophilic balance (HLB) 7-23, significantly
      enhanced PMO-induced exon-skipping in a green fluorescent protein (GFP) reporter
      based myoblast culture system. Application of optimized formulations of PCMs with
      PMO targeted to dystrophin exon 23 demonstrated a significant increase in exon
      skipping efficiency in dystrophic mdx mice. Consistent with our observations in
      vitro, optimization of molecular size and the HLB of pluronics are important
      factors for PCMs to achieve enhanced PMO delivery in vivo. Observed cytotoxicity
      of the PCMs was lower than Endo-porter and PEI 25 k. Tissue toxicity of PCMs in
      muscle was not clearly detected with the concentrations used, indicating the
      potential of the PCMs as effective and safe PMO carriers for treating diseases
      such as muscular dystrophy.

PMID- 23164939
TI  - Survival after segmentectomy and wedge resection in stage I non-small-cell lung
      cancer.
AB  - INTRODUCTION: Although lobectomy is considered the standard surgical treatment
      for stage IA non-small-cell lung cancer (NSCLC), wedge resection or segmentectomy
      are frequently performed on patients who are not lobectomy candidates. The
      objective of this study was to compare survival among patients with stage IA
      NSCLC, who are undergoing these procedures. METHODS: Using the Surveillance,
      Epidemiology and End Results registry, we identified 3525 patients. We used
      logistic regression to determine propensity scores for patients undergoing
      segmentectomy, based on the patient's preoperative characteristics. Overall and
      lung cancer-specific survival of patients treated with wedge resection versus
      segmentectomy was compared after adjusting, stratifying, or matching patients
      based on propensity score. RESULTS: Overall, 704 patients (20%) underwent
      segmentectomy. Analyses, adjusting for propensity scores, showed that
      segmentectomy was associated with significant improvement in overall (hazard
      ratio: 0.80, 95% confidence interval: 0.69-0.93) and lung cancer-specific
      survival (hazard ratio: 0.72, 95% confidence interval: 0.59-0.88) compared with
      wedge resection. Similar results were obtained when stratifying and matching by
      propensity score and when limiting analysis to patients with tumors sized less
      than or equal to 2 cm, or aged 70 years or younger. CONCLUSIONS: These results
      suggest that segmentectomy should be the preferred technique for limited
      resection of patients with stage IA NSCLC. The study findings should be confirmed
      in prospective studies.

PMID- 23164940
TI  - Underuse of radiotherapy in lung cancer has negative consequences for patients.
AB  - INTRODUCTION: Radiotherapy has proven to be an effective treatment when used
      alone or with other therapies. However, underuse of radiotherapy has been
      observed in various studies. The objective of this investigation was to assess
      the use of radiotherapy as initial treatment for lung cancer in a southern region
      of Europe. METHODS: A systematic review of lung cancer treatment guidelines and
      observational studies was performed to estimate expected radiation rates and the
      associated survival outcomes. We then reviewed the clinical and treatment records
      of all patients undergoing radiotherapy for lung cancer during 2007 in all the 12
      public hospitals in Andalusia with radiotherapy facilities. Data were grouped
      according to type of hospital, patient, treatment characteristics, histological
      type, and tumor stage. RESULTS: In 2007, of the 3051 patients estimated to be
      diagnosed with lung cancer, 610 were treated with initial radiotherapy with an
      overall radiation rate of 20%, which significantly differed among provinces
      (range, 8.5%-25.6%, p < 0.001). Given the expected radiation rate of 1383
      patients, 773 more patients of lung cancer (25%) should have been treated.
      According to the literature, the maximum increased survival attributable to the
      use of radiotherapy in patients diagnosed with non-small-cell lung cancer ranges
      from 1.8 to 14.1 months. The underuse estimated in the region would correspond to
      a loss of more than 3000 months in survival time. CONCLUSIONS: The observed
      underuse of radiotherapy in lung cancer in our region should be a matter of
      concern, given its negative and measurable impact on the survival of the
      patients.

PMID- 23164941
TI  - [Intestinal parasite diagnoses in Chad and North Cameroon, 1963-2009].
AB  - The authors report the results of parasitological analyses of stool samples in
      N'Djamena (Chad) since 1963 and in Garoua (North Cameroon) since 1990. The number
      of positive stool examinations has fallen, with a significant decline in
      helminthiases, although the level of protozoan infections has remained
      essentially the same.

PMID- 23164942
TI  - Exploring the diversity of SPRY/B30.2-mediated interactions.
AB  - The SPla/Ryanodine receptor (SPRY)/B30.2 domain is one of the most common folds
      in higher eukaryotes. The human genome encodes 103 SPRY/B30.2 domains, several of
      which are involved in the immune response. Approximately 45% of human SPRY/B30.2
      containing proteins are E3 ligases. The role and function of the majority of
      SPRY/B30.2 domains are still poorly understood, however, in several cases
      mutations in this domain have been linked to congenital disorders. The recent
      characterization of SPRY/B30.2-mediated protein interactions has provided
      evidence for a role of this domain as an adaptor module to assemble
      macromolecular complexes, analogous to Src homology (SH)2, SH3, and WW domains.
      However, functional and structural evidence suggests that SPRY/B30.2 is a more
      versatile fold, allowing a wide range of binding modes.

PMID- 23164943
TI  - Pulmonary hypertension in CKD.
AB  - Pulmonary arterial hypertension is a rare disease often associated with positive
      antinuclear antibody and high mortality. Pulmonary hypertension, which rarely is
      severe, occurs frequently in patients with chronic kidney disease (CKD). The
      prevalence of pulmonary hypertension ranges from 9%-39% in individuals with stage
      5 CKD, 18.8%-68.8% in hemodialysis patients, and 0%-42% in patients on peritoneal
      dialysis therapy. No epidemiologic data are available yet for earlier stages of
      CKD. Pulmonary hypertension in patients with CKD may be induced and/or aggravated
      by left ventricular disorders and risk factors typical of CKD, including volume
      overload, an arteriovenous fistula, sleep-disordered breathing, exposure to
      dialysis membranes, endothelial dysfunction, vascular calcification and
      stiffening, and severe anemia. No specific intervention trial aimed at reducing
      pulmonary hypertension in patients with CKD has been performed to date.
      Correcting volume overload and treating left ventricular disorders are factors of
      paramount importance for relieving pulmonary hypertension in patients with CKD.
      Preventing pulmonary hypertension in this population is crucial because even
      kidney transplantation may not reverse the high mortality associated with
      established pulmonary hypertension.

PMID- 23164944
TI  - Controlling protein-particle adsorption by surface tailoring colloidal alumina
      particles with sulfonate groups.
AB  - In this study, we demonstrate the control of protein adsorption by tailoring the
      sulfonate group density on the surface of colloidal alumina particles. The
      colloidal alumina (d(50)=179+/-8nm) is first accurately functionalized with
      sulfonate groups (SO(3)H) in densities ranging from 0 to 4.7SO(3)H nm(-2). The
      zeta potential, hydrophilic/hydrophobic properties, particle size, morphology,
      surface area and elemental composition of the functionalized particles are
      assessed. The adsorption of three model proteins, bovine serum albumin (BSA),
      lysozyme (LSZ) and trypsin (TRY), is then investigated at pH 6.9+/-0.3 and an
      ionic strength of 3mM. Solution depletion and zeta potential experiments show
      that BSA, LSZ and TRY adsorption is strongly affected by the SO(3)H surface
      density rather than by the net zeta potential of the particles. A direct
      correlation between the SO(3)H surface density, the intrinsic protein amino acid
      composition and protein adsorption is observed. Thus a continuous adjustment of
      the protein adsorption amount can be achieved between almost no coverage and a
      theoretical monolayer by varying the density of SO(3)H groups on the particle
      surface. These findings enable a deeper understanding of protein-particle
      interactions and, moreover, support the design and engineering of materials for
      specific biotechnology, environmental technology or nanomedicine applications.

PMID- 23164945
TI  - Contact nanofatigue shows crack growth in amorphous calcium phosphate on Ti, Co
      Cr and Stainless steel.
AB  - Fatigue testing of load-bearing coated implants is usually very time-consuming
      and so a new contact nanofatigue test using a nanoindenter has been evaluated. A
      cube corner indenter provided the fastest indication of failure, through crack
      formation, compared to a spherical indenter. Contact nanofatigue was performed on
      a sintered hydroxyapatite and then on amorphous calcium phosphate splats produced
      on titanium, stainless steel and Co-Cr surfaces, made either at room temperature
      or on 250 degrees C preheated surfaces. Sintered hydroxyapatite showed continual
      plastic deformation, but this is not that apparent for splats on metal surfaces.
      Substrate preheating was found to induce cracking in splats, explained by greater
      thermal residual stresses. Endurance during contact nanofatigue, measured as time
      to crack formation, was the lowest for splats on titanium followed by Co-Cr and
      stainless steel. The splat on titanium showed both cracking and plastic
      deformation during testing. Good agreement has been reached with previous studies
      with cracking directed to the substrate without splat delamination. Contact
      nanofatigue with the nanoindenter easily and quickly identifies cracking events
      that previously required detection with acoustic emission, and shows good
      feasibility for mechanical testing of discs and splats produced by thermal
      spraying, spray forming, laser-ablation, aerosol jet and ink jet printing.

PMID- 23164946
TI  - Doxorubicin-conjugated dendrimer/collagen hybrid gels for metastasis-associated
      drug delivery systems.
AB  - Metastasis is a characteristic property of cancer cells, which degrade
      extracellular matrix containing collagen. We prepared a polymer prodrug-embedded
      collagen gel for metastasis-associated drug delivery. A collagen peptide-modified
      dendrimer that attached doxorubicin (Dox) via a pH-degradable linkage was
      synthesized as a polymer prodrug. Compared with free Dox, the diffusion of the
      dendrimer prodrug from the collagen gel was suppressed. Highly invasive MDA-MB
      231 cells were more sensitive to the prodrug-hybrid collagen gel than poorly
      invasive MCF-7 cells, even though the cytotoxicity of the dendrimer prodrug by
      itself against these cells was almost identical. The cytotoxicity against MDA-MB
      231 cells decreased in the presence of a matrix metalloproteinase (MMP)
      inhibitor, suggesting that the dendrimer prodrug/collagen hybrid gel was affected
      by MMP activity. The dendrimer prodrug/collagen hybrid gel not only suppressed
      tumor growth but also attenuated metastatic activity in vivo. Therefore, the
      dendrimer prodrug-embedded collagen gel is useful for cancer chemotherapy.

PMID- 23164947
TI  - Advances in modifying fluorescein and rhodamine fluorophores as fluorescent
      chemosensors.
AB  - The fluorophores based on xanthene scaffolds, mainly containing rhodamine and
      fluorescein dyes, have attracted considerable interest from chemists due to their
      excellent photophysical properties such as high absorption coefficient, high
      fluorescence quantum yield, high photostability and relatively long wavelengths
      of fluorescence emission spectra. In this feature article, we overview the
      strategies in the development of fluorescent probes that are operating through
      the modification of the skeletons of fluorescein and rhodamine dyes, and the
      fluorescent behaviors of these probes toward specific analyte are discussed.

PMID- 23164948
TI  - An efficient dehydroxymethylation reaction by a palladium catalyst.
AB  - A general method for selective dehydroxymethylation has been discovered by using
      widely available Pd(OAc)(2). The present study offers a new synthetic strategy
      for the regioselective functionalization by employing the steric, electronic and
      coordinating nature of the hydroxymethyl (-CH(2)OH) group temporarily.

PMID- 23164949
TI  - Synergistic and antagonistic actions of acute or chronic social stressors and an
      endotoxin challenge vary over time following the challenge.
AB  - Acute stressor exposure and immunogenic challenges can synergistically increase
      behavioral, endocrine and neuroinflammatory responses, but much less is known
      about how chronic stressors influence the actions of immune challenges. In the
      present investigation we assessed the influence of bacterial endotoxin,
      lipopolysaccharide (LPS), administered on an acute chronic stressors backdrop, on
      sickness behavior, changes of circulating corticosterone and cytokine levels, and
      cytokine mRNA expression in the prefrontal cortex (PFC) and hippocampus. In this
      regard, it was of particular interest to determine whether the stressors would
      alter the temporal biological effects (onset and normalization) of LPS. There was
      a leftward shift in the temporal curve, in that sickness behavior, corticosterone
      and plasma IL-6 elevations among stressed mice appeared sooner after LPS
      treatment, but 3h after treatment corticosterone and IL-6 were lower than in
      nonstressed mice. In contrast, the stressor, especially when applied chronically,
      diminished the effects of LPS on TNF-alpha over the course of measurement,
      whereas effects on IL-10 were enhanced. In contrast to these peripheral effects,
      central cytokine mRNA expression, especially IL-1beta and TNF-alpha, were
      diminished 1.5h following stressor and LPS administration, but were then
      synergistically enhanced at 3h compared to non-stressed controls. Although acute
      and chronic stressors provoked similar behavioral and neuroendocrine responses
      when combined with LPS, the effects of chronic stressors and LPS on brain
      cytokines were generally diminished, particularly in the PFC. The implications of
      the temporal changes related to stressors and immune activation are discussed,
      and several possible mechanisms for these effects are suggested.

PMID- 23164950
TI  - The influence of glucocorticoid signaling on tumor progression.
AB  - The diagnosis of cancer elicits a broad range of well-characterized stress
      related biobehavioral responses. Recent studies also suggest that an individual's
      neuroendocrine stress response can influence tumor biology. One of the major
      physiological pathways altered by the response to unrelenting social stressors is
      the hypothalamic-pituitary-adrenal or HPA axis. Initially following acute stress
      exposure, an increased glucocorticoid response is observed; eventually, chronic
      stress exposure can lead to a blunting of the normal diurnal cortisol pattern.
      Interestingly, recent evidence also links high primary tumor glucocorticoid
      receptor expression (and associated increased glucocorticoid-mediated gene
      expression) to more rapid estrogen-independent breast cancer progression.
      Furthermore, animal models of human breast cancer suggest that glucocorticoids
      inhibit tumor cell apoptosis. These findings provide a conceptual basis for
      understanding the molecular mechanisms underlying the influence of the
      individual's stress response, and specifically glucocorticoid action, on breast
      cancer and other solid tumor biology. How this increased glucocorticoid signaling
      might contribute to cancer progression is the subject of this review.

PMID- 23164951
TI  - Short-term corticosterone treatment decreases the early CD8+ T cell response to
      simian virus 40 tumor antigen but has no impact on the late CD8+ T cell response.
AB  - CD8+ T cells (T(CD8)) help control tumor growth in vivo through recognition of
      distinct tumor antigens and cytolysis of tumor cells. The T(CD8) immune response
      in C57BL/6 mice to the Simian Virus 40 oncoprotein, large tumor antigen (Tag),
      targets multiple epitopes and is well-characterized. Epitope IV, an H-2K(b)
      restricted epitope, is immunodominant while epitope I, an H-2D(b)-restricted
      epitope is subdominant. GCs alter many aspects of T cell function. Indeed, the
      current studies demonstrate that exposure of mice to the immunosuppressive GC,
      corticosterone (CORT), over the entire course of the primary immune response
      limits activation of endogenous Tag-specific T(CD8). Even short-term CORT
      treatment from day -1 to day +2 post-immunization significantly reduced splenic
      size and the absolute number of Tag-specific T(CD8) on day 6 post-immunization.
      In vivo killing activity was also reduced. However, by day 10 post-immunization,
      the peak of the immune response, the absolute number of Tag-specific T(CD8) and
      their in vivo killing of epitope I or epitope IV-expressing target cells had
      recovered in CORT treated mice. Adoptive transfer of transgenic T cells post-CORT
      removal demonstrated that CORT decreased the ability of the endogenous antigen
      presenting cells to induce proliferation of the exogenous transgenic T cells.
      Combined, these studies have implications about the timing of clinical steroid
      treatment relative to immunization or adoptive transfer for cancer immunotherapy.

PMID- 23164952
TI  - Effect of HIV on survival in patients with non-small-cell lung cancer in the era
      of highly active antiretroviral therapy: a population-based study.
AB  - BACKGROUND: HIV-infected patients with lung cancer have been reported to have
      poorer survival than uninfected patients. Whether this outcome holds true in the
      era of highly active antiretroviral therapy (HAART) is unclear. We examined the
      effect of HIV infection on clinical outcome in patients with lung cancer who are
      also receiving HAART. METHODS: Patients diagnosed with non-small-cell lung cancer
      (NSCLC) from Jan 1, 2000, to Dec 31, 2005, with or without HIV infection were
      identified by querying the Surveillance, Epidemiology, and End Results registry
      and the Medicare lung cancer database. Survival analysis by stage and treatment
      delivered comparing the HIV-infected patients with uninfected controls was done
      with Kaplan-Meier and Cox models with propensity score adjustments. FINDINGS:
      71,976 patients with NSCLC were identified as uninfected controls and 322
      patients with NSCLC were identified in the HIV group; median age was 75 years for
      both groups. Median overall survival for all stages was 7.0 months (95% CI 7.0
      7.0) for uninfected controls versus 8.0 months (6.0-10.0) for the HIV group
      (p=0.16); for those with stage I/II disease it was 37.0 months (36.0-39.0) versus
      43.0 months (26.0-58.0; p=0.37); for those with stage IIIA/IIIB disease it was
      7.0 months (7.0-7.0) versus 3.0 months (2.0-8.0; p=0.051); and for those with
      stage IV disease it was 3.0 months for both groups (95% CI 3.0-3.0 for controls;
      2.0-5.0 for HIV group; p=0.77). After propensity score adjustment, the survival
      difference in stage IIIA/IIIB was no longer seen (hazard ratio 0.88; 95% CI 0.71
      1.09). The median survival for HIV infected patients with stage I or II NSCLC who
      underwent surgical resection was 58.0 months (95% CI 57.0-60.0) for uninfected
      controls versus 50.0 months (42.0 to unestimable) for the HIV group (p=0.88).
      INTERPRETATION: We noted no significant difference in clinical outcome between
      patients with HIV and uninfected controls with NSCLC. Survival after curative
      surgical resection in early-stage patients was similar in HIV-infected
      individuals and uninfected controls. These data suggest that HIV status should
      not affect therapeutic decision making in NSCLC. FUNDING: US National Cancer
      Institute (award number UC2CA148310).

PMID- 23164954
TI  - High signal contrast gating with biomodified Gd doped mesoporous nanoparticles.
AB  - Internally Gd doped mesoporous nanoparticles have been prepared and exhibit
      unprecedented relaxivities that are retained on external biomodification. In
      tuning diffusive water access, image contrast can be reversibly switched in the
      presence of a specific protein target.

PMID- 23164955
TI  - Five times novel aspects in cardiovascular anesthesia:  is this scary?

PMID- 23164956
TI  - Viruses and cancer, cats and cattle: a tribute to Bill Jarrett.

PMID- 23164958
TI  - Real-time transmission electron microscope observation of nanofriction at a
      single Ag asperity.
AB  - The observation of nanoscale deformation in real time is a significant step
      toward understanding the mechanisms of friction and lubrication. Our experimental
      setup of a micromachine combined with a transmission electron microscope allowed
      us to measure the deformation, force and cross-sectional area of a single Ag
      asperity during shear testing. The experimental results provided insight into one
      of the parameters that determines the frictional coefficient. Furthermore, we
      demonstrated that the energy loss associated with a shear fracture event is
      strongly correlated with the increase in total surface energy of the two surfaces
      formed here after the fracture of the nanocontact.

PMID- 23164957
TI  - Relationship between airborne detection of influenza A virus and the number of
      infected pigs.
AB  - Influenza A virus infects a wide range of species including both birds and
      mammals (including humans). One of the key routes by which the virus can infect
      populations of animals is by aerosol transmission. This study explored the
      relationship between number of infected pigs and the probability of detecting
      influenza virus RNA in bioaerosols through the course of an acute infection.
      Bioaerosols were collected using a cyclonic collector in two groups of 7 week-old
      pigs that were experimentally infected by exposure with a contact infected pig
      (seeder pig). After contact exposure, individual pig nasal swab samples were
      collected daily and air samples were collected three times per day for 8 days.
      All samples were tested for influenza by real-time reverse transcriptase (RRT)
      PCR targeting the influenza virus matrix gene. All pigs' nasal swabs became
      influenza virus RRT-PCR positive upon exposure to the infected seeder pig.
      Airborne influenza was detected in 28/43 (65%) air samples. The temporal dynamics
      of influenza virus detection in air samples was in close agreement with the nasal
      shedding pattern in the infected pigs. First detection of positive bioaerosols
      happened at 1 day post contact (DPC). Positive bioaerosols were consistently
      detected between 3 and 6 DPC, a time when most pigs were also shedding virus in
      nasal secretions. Overall, the odds of detecting a positive air sample increased
      2.2 times for every additional nasal swab positive pig in the group. In summary,
      there was a strong relationship between the number of pigs shedding influenza
      virus in nasal secretions and the generation of bioaerosols during the course of
      an acute infection.

PMID- 23164959
TI  - A procedure for testing across-condition rhythmic spike-field association change.
AB  - Many experiments in neuroscience have compared the strength of association
      between neural spike trains and rhythms present in local field potential (LFP)
      recordings. The measure employed in these comparisons, "spike-field coherence",
      is a frequency dependent measure of linear association, and is shown to depend on
      overall neural activity (Lepage et al., 2011). Dependence upon overall neural
      activity, that is, dependence upon the total number of spikes, renders comparison
      of spike-field coherence across experimental context difficult. In this paper, an
      inferential procedure based upon a generalized linear model is shown to be
      capable of separating the effects of overall neural activity from spike train-LFP
      oscillatory coupling. This separation provides a means to compare the strength of
      oscillatory association between spike train-LFP pairs independent of differences
      in spike counts. Following a review of the generalized linear modelling framework
      of point process neural activity a specific class of generalized linear models
      are introduced. This model class, using either a piece-wise constant link
      function, or an exponential function to relate an LFP rhythm to neural response,
      is used to develop hypothesis tests capable of detecting changes in spike train
      LFP oscillatory coupling. The performance of these tests is validated, both in
      simulation and on real data. The proposed method of inference provides a
      principled statistical procedure by which across-context change in spike train
      LFP rhythmic association can be directly inferred that explicitly handles between
      condition differences in total spike count.

PMID- 23164961
TI  - A general framework for extracting fetal magnetoencephalogram and audio-evoked
      responses.
AB  - The analysis of auditory evoked cortical responses in fetal
      magnetoencephalography (fMEG) can be used as an early marker of functional
      cerebral development. A major obstacle for this objective is the very low signal
      to-noise ratio of the fMEG recordings in presence of other biological
      contaminants (mainly maternal and fetal cardiac activities). Due to the fMEG
      nonstationarity and noise, the purpose of the present study is to improve the
      detection of the fetal auditory evoked response (fAER) by proposing a multi-stage
      framework for removing maternal and fetal artifacts using quasi-periodicity of
      cardiac activities, semi-blind source separation methods and detection of fAER
      using an ad hoc matched filter. The validation stage is performed using
      synchronous averaging, energy ratio comparison, statistical analysis of signal
      distribution, and the geometric localization of the fetal head and heart. The
      validation results show that the method can be effectively used in high precision
      fMEG and fAER applications.

PMID- 23164960
TI  - Novel technology for modulating locomotor activity as an operant response in the
      mouse: implications for neuroscience studies involving "exercise" in rodents.
AB  - We have developed a novel, low-cost device designed to monitor and modulate
      locomotor activity in murine subjects. This technology has immediate application
      to the study of effects of physical exercise on various neurobiological
      endpoints, and will also likely be useful in the study of psychomotor
      sensitization and drug addiction. Here we demonstrate the capacity of these
      devices to establish locomotor activity as an operant response reinforced by food
      pellet presentations, and show that schedules of reinforcement can reliably
      control this behavior. Importantly, these data show that varying degrees of
      increased locomotor activity (in other words, "exercise") can be elicited and
      maintained in mice by manipulating the schedule of reinforcement. Our findings
      argue that the present technology might reduce the imposition of stress and
      motivational bias inherent in more traditional procedures for establishing
      exercise in laboratory rodents, while allowing for true random assignment to
      experimental groups. As interest in physical exercise as a modulating factor in
      numerous clinical conditions continues to grow, technologies like the one
      proposed here are likely to become critical in conducting future experiments
      along these lines.

PMID- 23164962
TI  - Cultures of astroglial cells derived from brain of adult cichlid fish.
AB  - Astroglial cells in teleost fish occur mostly as radial glia. We established a
      culture system derived from brain tissue of mature cichlid fish Astatotilapia
      burtoni to study fish astroglial cells in more detail. Cells were passaged
      several times to expand the cultures, and could be kept in vitro for several
      months. The cell identity was tested by the presence of glial fibrillary acidic
      protein (GFAP); in addition, cells expressed the tight junction adaptor protein
      zonula occludens-1 (ZO-1) known to be present on astroglial cells in fish brain.
      This is consistent with the radial and epithelial nature of fish astroglial cells
      derived from neuroepithelium. To characterize the properties of cultured
      astroglial cells we challenged them in hypo-osmotic conditions. Cells reacted
      with volume increase, slower but similar to mammalian astrocytes. We also tested
      whether astroglial cells support growth during axonal elongation. We placed
      retinal explants on astroglial cultures and found neurites extending readily on
      these cells, compared to controls which showed no or little growth. Thus, we
      established a culture system for astroglial cells from the mature fish brain that
      demonstrates their neuroepithelial properties. This culture system will be useful
      to study functions in which glial cells are thought to play an important role:
      e.g. regulation of water homeostasis and supporting axonal regeneration.

PMID- 23164963
TI  - [Profession and research: an invitation to dis- and/or con-sent].

PMID- 23164964
TI  - [Hand hygiene of medical and nursing students during clinica rotations: a pilot
      study on knowledge, attitudes and impact on bacterial contamination].
AB  - Hand hygiene in nursing and medical students during training: a pilot study on
      knowledge, practices and impact on bacterial contamination. INTRODUCTION: Despite
      exhaustive guidelines on hand hygiene (HH), compliance in health care
      professionals is reported to be low. In order to improve adherence with HH,
      interventions on students' education should be effective. AIM: To describe the
      knowledge, behavior and hand hygiene (HH) practices in nursing and medical
      students. The results of the pilot study are presented. METHODS: A questionnaire
      designed to investigate knowledge on HH and its practical implementation was
      administered to a sample of 50 nursing and 50 medical students. Data collected
      were associated with hand contamination measured at the beginning and at the end
      of the training shift. RESULTS: All nursing students performed HH with a
      significantly higher frequency compared to medical students. At the end of
      training, total bacterial counts were significantly reduced in both groups, but
      more in nursing students. Total bacterial count increased in absence of hygienic
      practices and the most effective procedure was the alternate use of conventional
      hand washing and alcohol-based hands rubs. The knowledge of both groups was
      adequate, although some differences were observed. CONCLUSIONS: At the beginning
      of their course, nursing students are educated to correct practices that
      implement during practical training. Medical students receive information on HH
      later in their education and pay less attention to these aspects, also due to the
      limited number of physical contacts with patients. Thus, the contents on HH
      should be anticipated before the start of the training activity.

PMID- 23164965
TI  - [Randomized controlled trial on the effectiveness of Corpitolinol 60 in the
      prevention of pressure sores in patients undergoing surgery].
AB  - Randomized controlled trial on the effectiveness of Corpitolinol 60 in the
      prevention of pressure sores in surgical patients. INTRODUCTION: The risk of
      pressure sores in surgical patients is widely recognised. The Corpitolinol 60
      (Sanyrene(r)) applied on compressed areas seems to reduce the risk of pressure
      sores. AIM: To assess the efficacy of Corpitolinol 60 in preventing pressure
      sores in the operatory theatre. METHODS: The open label randomized clinical trial
      was conducted in 5 operating theatres of Northen Italy. Patients were randomized
      to receive Corpitolinol 60 in areas undergoing compression. Experimental group
      and controls were treated with usual measures for preventing pressure sores. The
      lesions were staged according to NPUAP up to 24 hours after surgery. RESULTS:
      Three-hundred-one patients were randomized (155 in the Sanyrene(r) group and 143
      controls). The main variables predictive of pressure sores risk (ASA class, sex,
      age, duration of the surgery, and BMI) were comparable across groups. At the end
      of the surgery 71 patients (23.8%) in the experimental group and 47 controls
      (30.8%) had a pressure sore (p 0.006; RR 1.81 IC95% 1.17-2.79). Twelve and 24
      hours after surgery the differences between groups were not significant.
      CONCLUSIONS: The aim of reducing pressure sores was not reached for patients
      treated with Corpitolinol 60.

PMID- 23164966
TI  - [The observation as a strategy to generate research questions: experience in
      psychiatry].
AB  - The observation as a strategy to generate research questions: an experience in a
      psychiatric ward. INTRODUCTION: The daily activity could, and should, be the
      natural setting where research hypotheses are generated, specifically in areas of
      care where the frequency of problems Evidence Based Practice "orphans" is high,
      such as psychiatry. AIMS: To test the possibility and the yeld of identifying
      formulating research needs and hypotheses from - within nursing duties. METHODS:
      Prospective registration of clinical conditions decisions to be taken from a
      position of substantial uncertainty over a pilot period of 7 working days.
      RESULTS: Up to 39 diagnostic, therapeutic, rehabilitation, organizational,
      behavioral problems have been and included in the diary and associated with one
      or more hypothesis considered to be a potential need/opportunity for
      observational and/or experimental research. CONCLUSIONS: Psychiatry is very
      rarely among the priorities of nursing attention and research, thus exposing
      nursing care to a systematic risk of empirical-uncontrolled practices.

PMID- 23164967
TI  - [Hypodermoclysis hydration in the elderly].
AB  - Hydration with hypodermoclysis in elderly patients. Hypodermoclysis is a
      technique which consists in the administration of fluids into the subcutaneous
      tissue for the treatment of mild to moderate dehydration. The article starts from
      the case of a 74 year old man that, after a stroke, was unable to eat or drink,
      and was then hydrated with continuous hypodermoclysis for 45 days, obtaining a
      recovery of the clinical and psychological conditions. An update of the available
      knowledge on hypodermoclisis, together with some comments on the clinical case
      are presented.

PMID- 23164968
TI  - [The role of the mind and survival in cancer patients].
AB  - The role of mind and survival in cancer patients. A relationship between
      psychological reactions and survival in cancer patients has been shown in several
      studies. A recent editorial illustrates how interventions providing social and
      emotional support at the end of life may positively influence the physiological
      stress response systems that can affect survival.

PMID- 23164969
TI  - [An extreme case of family violence against a child].
AB  - An extreme case of family violence against a child. Marianna is a child dead by
      hardships. The case, apparently far from nursing daily practice, is the occasion
      for reflecting how often the nursing profession witnesses situations at risk of
      remaining invisible unless somebody decides to take them on by collecting data,
      reporting signals, carefully observing.

PMID- 23164970
TI  - [Report SVIMEZ: population, education and the labor market and migration].
AB  - SVIMEZ REPORT: Population, school, job market, migrations. The Svimez, a private
      non profit institution, is an association for the development of business and
      industries in the south of Italy, whose aim is the study of the economy of the
      South of Italy to propose development programs. The report on the Economy in the
      South of Italy is the main annual yearly report since 1974. The main indicators
      and the development of southern economy in several key sectors are presented and
      discussed, each year focusing on different specific problems. AIR has already
      proposed contributions on the gap between north and south to reflect on
      inequalities. The relationship between economy, wellbeing and health has been
      demonstrated. The section on school, job market and migrations is presented.

PMID- 23164972
TI  - Disparities in work, risk and health between immigrants and native-born
      Spaniards.
AB  - The probability of acquiring a permanent disability is partly determined by
      working and contractual conditions, particularly exposure to job risks. We
      postulate a model in which this impact is mediated by the choice of occupation,
      with a level of risk associated with it. We assume this choice is endogenous and
      that it depends on preferences and opportunities in the labour market, both of
      which may differ between immigrants and natives. To test this hypothesis we apply
      a bivariate probit model, in which we control for personal and firm
      characteristics, to data for 2006 from the Continuous Sample of Working Lives
      provided by the Spanish Social Security system, containing records for over a
      million workers. We find that risk exposure increases the probability of
      permanent disability--arising from any cause--by almost 5%. Temporary employment
      and low-skilled jobs also have a positive impact. Increases in education reduce
      the likelihood of disability, even after controlling for the impact of education
      on the choice of (lower) risk. Females have a greater probability of becoming
      disabled. Migrant status--with differences among regions of origin--significantly
      affects both disability and the probability of being employed in a high-risk
      occupation. In spite of immigrants' working conditions being objectively worse,
      they exhibit a lower probability of becoming disabled than natives because the
      impact of such conditions on disability is much smaller in their case. Time
      elapsed since first enrolment in the Social Security system increases the
      probability of disability in a proportion similar to that of natives, which is
      consistent with the immigrant assimilation hypothesis. We finally conclude that
      our theoretical hypothesis that disability and risk are jointly determined is
      only valid for natives and not valid for immigrants, in the sense that, for them,
      working conditions are not a matter of choice in terms of health.

PMID- 23164973
TI  - Liquid immiscibility in an Fe-Cu alloy by molecular dynamics simulation.
AB  - Liquid-liquid phase segregation in an Fe-Cu melt is investigated by molecular
      dynamics (MD) simulation based upon a newly developed embedded atom method due to
      Bonny. The partial pair correlation functions (PPCF) of liquid Fe(50)Cu(50) at a
      temperature of 1873 K show stronger interaction of homogeneous atom pairs. The
      coordination number (CN) of Cu-Cu and Fe-Fe in Fe(50)Cu(50) melt is about 11,
      much higher than that of Fe-Cu. Liquid-liquid phase segregation has also been
      observed clearly by the atom snapshot method. The calculated enthalpy of mixing
      is positive in the whole concentration range and the Bhatia-Thornton (BT)
      structure factor S(CC)(q) increases sharply at lower q, which are all typical
      features of dense fluid that exhibits a phase segregation tendency. Our present
      work provides an understanding of atomic-scale phase segregation in liquid Fe-Cu
      alloy.

PMID- 23164974
TI  - On the role of extracellular polymeric substances during early stages of Xylella
      fastidiosa biofilm formation.
AB  - The structural integrity and protection of bacterial biofilms are intrinsically
      associated with a matrix of extracellular polymeric substances (EPS) produced by
      the bacteria cells. However, the role of these substances during biofilm adhesion
      to a surface remains largely unclear. In this study, the influence of EPS on
      Xylella fastidiosa biofilm formation was investigated. This bacterium is
      associated with economically important plant diseases; it presents a slow growth
      rate and thus allows us to pinpoint more precisely the early stages of cell
      surface adhesion. Scanning electron microscopy and atomic force microscopy show
      evidence of EPS production in such early stages and around individual bacteria
      cells attached to the substrate surface even a few hours after inoculation. In
      addition, EPS formation was investigated via attenuated total reflectance (ATR)
      Fourier transform infrared spectroscopy (FTIR). To this end, X. fastidiosa cells
      were inoculated within an ATR liquid cell assembly. IR-ATR spectra clearly reveal
      EPS formation already during the early stages of X. fastidiosa biofilm formation,
      thereby providing supporting evidence for the hypothesis of the relevance of the
      EPS contribution to the adhesion process.

PMID- 23164975
TI  - Development of an integrative practice placement model for students in health
      care.
AB  - VireTori, the interprofessional Empowerment Market, is both an easily accessible
      health service point for citizens and a provider of placements for students. This
      study describes undergraduate health care students' experiences of learning at
      VireTori, and explores how the integrative pedagogy model was executed during
      student placements. The integrative pedagogy model was developed for the
      educational framework of the placement. The participants of the study were 42
      undergraduate students. The data were collected in 2010 through six focus-group
      interviews and background questionnaires, and were analysed using inductive
      content analysis. The results were categorised into personal, collaborative and
      organisational learning contexts and reported as the experiences of happy and
      unhappy students. Third-year students with a five-week or longer placement had
      more positive experiences than the fourth-year students with a one-week
      placement. There were great differences between the experiences of happy and
      unhappy students concerning professional roles, work orientations and scopes of
      action, and these were not entirely connected with the length of placement.
      Health care students can gain expertise through a practice placement in which the
      principles of integrative pedagogy have been adopted. Critique concerning the
      model and VireTori framework will be presented. 

PMID- 23164976
TI  - Practical coaching by mentors: student midwives' perceptions.
AB  - OBJECTIVE: The objective of this paper was to explore some of the specific
      strategies used by midwife mentors to mediate practice learning from the
      perspective of a sample of student midwives. DESIGN: Audio-diaries were completed
      by student midwives over ten days in practice and were transcribed using
      discourse analysis. A sub-sample from 19 students' learning diaries from a
      national midwifery education study conducted by Pope et al. (2003) has been
      selected as the diaries informed a separate study. PARTICIPANTS: The sample of
      student midwives were studying on degree and diploma programmes at five case
      study sites in England. MAIN FINDINGS: Students described how their mentors
      apparently successfully tailored their teaching to the students' needs. However,
      there was perceived disparity in techniques used by individual mentors to pass on
      their practice know-how. The findings demonstrate the pivotal role of the mentor
      for 'scaffolding' learning and also using 'fading' techniques within a cognitive
      apprenticeship model. KEY CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: Mentors need
      assistance to adapt their mentoring styles and to use a wider range of
      instruction strategies for student midwives. This has practical implications for
      mentor preparation programmes and mentorship models.

PMID- 23164977
TI  - Self-reported depression and physical activity in adults with mobility
      impairments.
AB  - OBJECTIVE: To test hypothesized associations between depression and physical
      activity among adults with multiple sclerosis (MS), spinal cord injury (SCI),
      muscular dystrophy (MD), and postpolio syndrome (PPS). DESIGN: Cross-sectional
      survey. SETTING: Survey responses collected from individuals in the Washington
      state area (participants with SCI) and across the United States (participants
      with MS, MD, and PPS). PARTICIPANTS: Convenience sample of participants were
      surveyed (N=1676; MD, n=321; PPS, n=388; MS, n=556; SCI, n=411). INTERVENTIONS:
      Not applicable. MAIN OUTCOME MEASURES: The Patient Health Questionnaire-9 (PHQ-9)
      assessing depressive symptoms and the International Physical Activity
      Questionnaire (IPAQ) and Godin Leisure Time Exercise Questionnaire (GLTEQ)
      assessing physical activity. RESULTS: The average age was 56 years, 64% were
      women, 92% were white, 86% had a high school degree or higher, and 56% walked
      with an assistive device or had limited self-mobility. The IPAQ and GLTEQ
      explained a small but statistically significant and unique amount of the variance
      in PHQ-9 scores in all diagnostic groups, with no significant differences in the
      relation by condition, age, or mobility status (IPAQ R(2)=.004; GLTEQ R(2)=.02;
      both P<.02). CONCLUSIONS: Both physical activity measures demonstrated a small
      but statistically significant association with depression in all 4 diagnostic
      groups. Research is needed to determine longitudinal relations and whether
      physical activity interventions could promote improved mood in adults with
      physical disabilities.

PMID- 23164978
TI  - Interobserver agreement of magnetic resonance imaging signs of osteomyelitis in
      pelvic pressure ulcers in patients with spinal cord injury.
AB  - OBJECTIVE: To examine the interobserver reliability of magnetic resonance imaging
      (MRI) signs of osteomyelitis in complex chronic pressure ulcers in patients with
      spinal cord injury (SCI). DESIGN: Retrospective review study. SETTING: Specialist
      SCI rehabilitation center. PARTICIPANTS: Adult patients with SCI and pressure
      ulceration investigated with MRI. INTERVENTIONS: Analysis of MRI examinations and
      clinical records collected over a 4-year period. Images were independently
      assessed by 2 experienced radiologists for osteomyelitis based on assigned
      predictive indicators including cortical bone erosion, soft tissue edema, deep
      collections, heterotopic new bone, hip effusion, and abnormal signal change of
      the marrow. MAIN OUTCOME MEASURES: Interobserver agreement for indicative MRI
      signs of osteomyelitis in complex pressure ulcers. RESULTS: Thirty-seven patients
      underwent 41 MRI scans. Concordance for marrow edema was 71% on both short tau
      inversion recovery and T1-weighted sequences, and for cortical erosion was 85%.
      CONCLUSIONS: For the assessment of pelvic osteomyelitis related to pressure
      ulcers, the T1-weighted MRI signal for marrow edema and cortical erosion has
      strong interobserver agreement.

PMID- 23164979
TI  - Defining substantial clinical benefit for patient-rated outcome tools for
      shoulder impingement syndrome.
AB  - OBJECTIVE: To define for 2 shoulder outcomes scales the substantial clinical
      benefit (SCB)-a metric that defines the change amount associated with patient
      perception of a large meaningful improvement and that can be used to interpret
      change over time in the outcome score. DESIGN: Cohort. SETTING: Clinic.
      PARTICIPANTS: Patients (N=74) with shoulder impingement syndrome. INTERVENTIONS:
      Standardized exercise and manual therapy for 6 weeks, and outcome measures
      completed at initial evaluation, discharge, and 6 to 8 weeks postdischarge. MAIN
      OUTCOME MEASURES: Disabilities of the Arm, Shoulder and Hand (DASH), Pennsylvania
      Shoulder Score (Penn), and a 13-point Global Rating of Change (GROC). Patients
      were classified as "substantially improved" when they reported "quite a bit
      better" (11) or greater on the GROC at discharge and again 6 to 8 weeks after
      discharge. Patients with GROC <11 at discharge or follow-up were classified as
      "nonsubstantially improved." The percentage and raw points change in the Penn and
      DASH that corresponded with patient-rated substantial improvement was determined
      with receiver operator characteristic (ROC) analyses. RESULTS: ROC analyses
      revealed the SCB for the DASH was 40% (area under the curve [AUC]=.79; confidence
      interval [CI], .69-.89) and 11 points (AUC=.63; CI, .50-.76); and for the Penn,
      20% (AUC=.76; CI, .65-.87) and 21 points (AUC=.80; CI, .69-.90). CONCLUSIONS: The
      SCB of 40% for the DASH, and 20% and 21 points for the Penn represents
      substantial improvement over 6 weeks of care, which was sustained at 12 weeks.
      The SCB of 11 points for the DASH is not recommended for use because of poor
      discrimination. The SCB can be used to enable clinical decision-making and in
      future clinical trials. Alternative approaches such as the within- and between
      group change values can produce different SCB values.

PMID- 23164980
TI  - Predicting 3-year incident mobility disability in middle-aged and older adults
      using physical performance tests.
AB  - OBJECTIVE: To identify a standard physical performance test, which can predict 3
      year incident mobility disability independent of demographics. DESIGN:
      Longitudinal cohort study. SETTING: Population-based middle-aged and older adult
      cohort assessment performed at a local geriatric clinical center. PARTICIPANTS:
      Community-living middle-aged and older persons (age, 50-85y) without baseline
      mobility disability (N=622). INTERVENTIONS: Not applicable. MAIN OUTCOME
      MEASURES: Mobility disability was ascertained at baseline and at 3-year follow-up
      using an established self-report method: self-reported inability to walk a
      quarter mile without resting or inability to walk up a flight of stairs
      unsupported. Physical performance tests included self-selected usual gait speed,
      time required to complete 5 times sit-to-stand (5TSTS), and 400-m brisk walking.
      Demographic variables age, sex, height, and weight were recorded. RESULTS:
      Overall, 13.5% participants reported 3-year incident mobility disability. Usual
      gait speed <1.2m/s, requiring >13.6 seconds to complete 5TSTS, and completing
      400m at <1.19m/s walking speed were highly predictive of future mobility
      disability independent of demographics. CONCLUSIONS: Inability to complete 5TSTS
      in <13.7 seconds can be a clinically convenient guideline for monitoring and for
      further assessment of middle-aged and older persons, in order to prevent or delay
      future mobility disability.

PMID- 23164981
TI  - A photoconductive charge-transfer crystal with mixed-stacking donor-acceptor
      heterojunctions within the lattice.
AB  - A pyrene derivative as the donor and a butyl-viologen as the acceptor were used
      to construct a novel charge-transfer cocrystal consisting of mixed-stacking
      structure and having switchable photoconductivity stemming from the donor
      acceptor heterojunctions within the lattice.

PMID- 23164982
TI  - Detection of small differences in the hydrophilicity of ions using the LCST-type
      phase transition of an ionic liquid-water mixture.
AB  - The phase separation temperature of the tetrabutylphosphonium trifluoroacetate
      water mixture, which undergoes a lower critical solution temperature-type phase
      transition, is highly sensitive to the hydrophilicity of added salts; this system
      can be used to compare the hydrophilicity of the added ions.

PMID- 23164983
TI  - Improvement of the cellular quality of cryopreserved bovine blastocysts
      accompanied by enhancement of the ATP-binding cassette sub-family B member 1
      expression.
AB  - The ATP-binding cassette sub-family B member 1 (ABCB1) plays a critical role in
      maintaining the metabolic capability of cells as an efflux transporter that pumps
      xenobiotics out of cells. We investigated the effects of highly expressed ABCB1
      on the development and viability of cryopreserved bovine embryos. The ABCB1 level
      in cultured bovine embryos was decreased during development to blastocyst-stage
      compared to germinal vesicle- and second metaphase-stage oocytes. When bovine
      embryos were cultured with forskolin and/or rifampicin, the ABCB1 level was
      significantly increased in blastocysts but embryo development was not
      significantly improved. After embryo cryopreservation, highly ABCB1-expressed
      blastocysts exhibited significant increases in viability and hatching rates. The
      high viability of the cryopreserved blastocysts was accompanied by a significant
      increase in cell proliferation during culture for 48 h. Thus, ABCB1 is expressed
      in bovine oocytes and embryos, and the cellular quality of bovine blastocysts is
      improved by the enhancement of ABCB1 expression.

PMID- 23164984
TI  - Placental concentrations of mercury, lead, cadmium, and arsenic and the risk of
      neural tube defects in a Chinese population.
AB  - To examine whether in utero exposure to mercury (Hg), cadmium (Cd), lead (Pb) and
      arsenic (As) is associated with an elevated neural tube defects (NTDs) risk,
      placental concentrations of total Hg, Cd, Pb and As were measured with an
      inductively coupled plasma mass spectrometer (ICP-MS) in 36 anencephaly and 44
      spina bifida cases as well as in 50 healthy controls. The median Hg concentration
      in the NTD cases (2.25 ng/g) was higher than that of the controls (1.16 ng/g).
      The odds ratio (OR) for an Hg concentration above the median was 8.80 (95% CI
      3.80-20.36) for the NTD cases. NTD risks increased for the second and third high
      levels of the concentrations, with ORs of 2.70 (95% CI 1.13-6.43) and 18.20 (95%
      CI 5.45-60.73), respectively. Therefore, higher placental levels of Hg are
      associated with an elevated risk of NTDs.

PMID- 23164985
TI  - Reproductive and developmental toxicity screening test of 3-cyanopyridine in
      rats.
AB  - Crl:CD(SD)rats were given 3-cyanopyridine by gavage at 0, 5, 30 or 180 mg/kg/day.
      Males were dosed for 42 days beginning 14 days before mating, and females for 40
      53 days beginning 14 days before mating to day 3 of lactation, including
      throughout the mating and gestation periods. General toxicity, mainly liver
      damage, was observed in males at >=30 mg/kg/day and in females at >=5 mg/kg/day.
      Sertoli cell vacuolation was observed at 180 mg/kg/day, and spermatocyte damages
      were observed at >=30 mg/kg/day. Effects on estrous cycles, corpora lutea and
      implantations, and unsuccessfully mated females, despite additional mating, were
      observed at 180 mg/kg/day. Delayed initiation of delivery, dystocia, and deaths
      or moribundities of pregnant females were observed at 180 mg/kg/day, and only two
      pregnant rats delivered live pups at that dose. The NOAEL for
      reproductive/developmental toxicity was concluded to be 30 mg/kg/day.

PMID- 23164987
TI  - Ageing:  biology and nutrition.

PMID- 23164986
TI  - L-arginine, tetrahydrobiopterin, nitric oxide and diabetes.
AB  - PURPOSE OF REVIEW: The endothelial isoform of nitric oxide synthase (eNOS) is
      constitutively expressed but dynamically regulated by a number of factors.
      Building our knowledge of this regulation is necessary to understand and modulate
      the bioavailability of nitric oxide, central to the cardiovascular complications
      of diabetes and other diseases. This review will focus on the eNOS substrate (L
      arginine), its cofactor (tetrahydrobiopterin), and mechanisms related to the
      uncoupling of eNOS activity. RECENT FINDINGS: The global arginine bioavailability
      ratio has been proposed as a biomarker reflective of L-arginine availability,
      arginase activity, and citrulline cycling, as all of these processes impact eNOS
      activity. The failure of oral supplementation of tetrahydrobiopterin to recouple
      eNOS has emphasized the importance of the tetrahydrobiopterin to dihydrobiopterin
      ratio. Identification of transporters for biopterin species as well as signals
      that regulate endogenous arginine production have provided insight for
      alternative strategies to raise endothelial tetrahydrobiopterin levels while
      reducing dihydrobiopterin and alter eNOS activity. Finally, new information about
      redox regulation of eNOS itself may point to ways of controlling oxidative stress
      in the vasculature. SUMMARY: Restoring proper eNOS activity is key to
      ameliorating or preventing cardiovascular complications of diabetes. Continued
      investigation is needed to uncover new means for maintaining endothelial nitric
      oxide bioavailability.

PMID- 23164988
TI  - Influence of uracil on bacterial translocation in an intestinal obstruction model
      in rats.
AB  - INTRODUCTION: Bacterial translocation occurs when intestinal mucosa and the
      intestinal wall lose their barrier properties against bacteria such as in the
      case of intestinal obstruction. Enteral nutrition with immunonutrients
      strengthens the immune system and thickens the intestinal barrier thus preventing
      bacterial translocation. AIM: The purpose of this study is to investigate the
      effect of uracil which is an immunonutrient on bacterial translocation using rats
      with intestinal obstruction as a model. METHODS: Wistar albino rats were divided
      into three groups. The control group was fed with standard chow diet, while the
      other two groups were fed with uracil-supplemented chow diet. The rats were fed
      with these diets for seven days. And the end of the feeding period all groups
      were submitted intestinal obstruction and injected with (99m)Tc labeled
      Escherichia coli into the rats' terminal ileum under anesthetic. The rats were
      sacrificed 24 h later. Their blood, mesenteric lymph nodes (MLN), liver, spleen,
      lung and ileum were removed to determine level of radioactivity. RESULTS: When
      compared with the control group it was determined that uracil supplementation
      reduced the level of bacterial translocation. CONCLUSION: Uracil may be used in
      the prevention of bacterial translocation in cases of intestinal obstruction
      because it strengthens the intestinal barrier and the immune system. However,
      more studies are needed to clearly explain the mechanism behind uracil's
      beneficial role here.

PMID- 23164989
TI  - Effect of standard anthracycline based neoadjuvant chemotherapy on circulating
      levels of serum IL-6 in patients of locally advanced carcinoma breast - a
      prospective study.
AB  - BACKGROUND: Elevated IL-6 levels have been associated with advanced stage of
      breast cancer and metastasis-related morbidity. The present prospective study was
      carried out to assess the effect of neoadjuvant chemotherapy on circulating
      levels of serum IL-6 in patients of locally advanced carcinoma breast. MATERIALS:
      All locally advanced carcinoma breast cases presenting to the surgery out
      patient's department were included in the study excluding pregnant or lactating
      females and those patients who were unfit for anthracycline based chemotherapy. A
      total of 30 cases were included. The various parameters that were evaluated
      include detailed clinico-pathological profile and IL-6 levels. Clinical staging
      using TNM classification was performed in all enrolled patients. This included
      documenting tumor size (on USG), node status and metastatic workup. First blood
      sample was collected before start of any treatment. Second blood sample was
      collected after 3 cycles of chemotherapy. Blood was centrifuged within 30 min and
      serum kept at -80  degrees C until analysis for IL-6. IL-6 levels were quantified
      by ELISA. RESULTS: Majority of patients presented in stage T3N1M0 (66.66%). The
      serum level of IL-6 increased as the disease progressed from T3N1M0 to T4dN2M0
      (41.4 +/- 31.9 pg/ml vs. 164.0 +/- 31.1 pg/ml respectively). A progressive
      reduction in IL-6 levels with subsequent cycles of chemotherapy was observed
      which was statistically significant (from 72.8 +/- 56.0 pg/ml to 47.0 +/- 61.9
      pg/ml; p value 0.002 wilcoxan signed rank test). CONCLUSION: Our study shows a
      consistent decline in the IL-6 levels with chemotherapy. Upon ratification of our
      findings by large population based multi centric studies, we may state with
      conviction that a single blood test as serum level of IL6 will prove beneficial
      in assessing the efficacy of chemotherapy.

PMID- 23164990
TI  - Effects of a cost-effective surgical workflow on cosmesis and patient's
      satisfaction in open thyroid surgery.
AB  - PURPOSE: In thyroid surgery, minimally invasive procedures are thought to improve
      cosmesis and patient's satisfaction. However, studies using standardized tools
      are scarce, and results are controversial. Moreover, minimally invasive
      techniques raise the question of material costs in a context of health spending
      cuts. The aim of the present study is to test a cost-effective surgical workflow
      to improve cosmesis in conventional open thyroid surgery. METHODS: Our study ran
      between January 2009 and November 2010, and was based on a prospectively
      maintained thyroid surgery register. Patients operated for benign thyroid
      diseases were included. Since January 2010, a standardized surgical workflow was
      used in addition to the reference open procedure to improve the outcome. Two
      groups were created: (1) G1 group (patients operated with the reference
      technique), (2) G2 group (patients operated with our workflow in addition to
      reference technique). Patients were investigated for postoperative outcomes, self
      evaluated body image, cosmetic and self-confidence scores. RESULTS: 820 patients
      were included in the present study. The overall body image and cosmetic scores
      were significantly better in the G2 group (P < 0.05). No significant difference
      was noted in terms of surgical outcomes, scar length, and self-confidence.
      CONCLUSIONS: Our surgical workflow in conjunction with the reference technique is
      safe and shows significant better results in terms of body image and cosmesis
      than do the reference technique alone. Thus, we recommend its implementation in
      order to improve outcomes in a cost-effective way. The limitations of the present
      study should be kept in mind in the elaboration of future studies.

PMID- 23164991
TI  - A medical school experience with three port laparoscopic cholecystectomy with a
      new modification in technique.
AB  - INTRODUCTION: The three port laparoscopic cholecystectomy is a recognized entity
      in the surgical management of gallstone disease. We report our experience and
      feasibility of three port laparoscopic cholecystectomy with a new modification in
      technique. METHODS: To assess the feasibility and safety of three-port
      laparoscopic cholecystectomy with a different port placement, we undertook a
      prospective study with 50 patients at government medical college, Srinagar,
      Kashmir, India between Jan 2010 and Jan 2011. Our study offered a benefit of
      concealed third port designed around umbilicus over the conventional three port
      laparoscopic cholecystectomy. A single surgeon did all the cases and definite
      criteria of simple cases of gallstone disease patterned on clinical and
      radiological grounds. RESULTS: 50 cases of gallstone disease were subjected to
      the new technique of three port laparoscopic cholecystectomy during a period one
      year. 34 cases were females and 16 were males. The age range of our patients was
      between 20 and 55 years with the median age of 33 years. Mean Body mass index 30
      (range 25-35). Mean operative time was 30 min (range 15-45 min) and a follow up
      [period ranged from 9 to 12 months]. No cases were converted to open though two
      cases required an additional port in the right hypochondrium for retraction. We
      did not encounter any untoward mishaps during surgery. CONCLUSION: Three port
      laparoscopic cholecystectomy with our modification of the third port placement at
      a different site received good results and patient satisfaction. Moreover the
      placement of third port at a consealed area around umbilicus apparently gives it
      an appearance of two port laparoscopic cholecystectomy with an addition of
      technical ease.

PMID- 23164992
TI  - Hepatic resection for metastatic melanoma in The Netherlands:  survival and
      prognostic factors.
AB  - Patients with hepatic metastases of melanoma have a very poor prognosis, with a
      median overall survival of less than 6 months. There are several small
      heterogeneous studies that have shown an association with prolonged survival in
      those patients treated with hepatic resection, but the role of surgery remains
      unclear. We evaluated the safety and efficacy of hepatic resection in a
      population-based study in the Netherlands for patients with metastatic melanoma
      and assessed the factors that could affect disease-free and overall survival.
      Patients with hepatic melanoma metastases who underwent potentially curative
      resection were identified between 1994 until 2010 using the PALGA database, a
      nation-wide network and registry of histopathology and cytopathology in the
      Netherlands. They were retrospectively evaluated for clinical and pathological
      factors with respect to recurrence and survival using Kaplan-Meier curves to
      assess survival and univariate regression analysis for the assessment of
      potential prognostic factors. A total of 32 patients were identified in 15
      hospitals, 19 men and 13 women. The median age of the patients at the time of
      hepatic resection was 52 years (range 27-69). Postoperative complications
      occurred in five patients (15%), without postoperative mortality. The median
      follow-up was 21 months (range 3-65). The median disease-free survival was 11
      months (range 0-57) and the median overall survival was 29 months (range 4-66).
      Significant prognostic factors for overall survival in univariate analysis were
      the distribution and number of metastases, as well as the type of hepatic
      resection (major or minor). Hepatic resection in patients with resectable
      metastatic melanoma is safe and might be associated with a prolonged survival in
      a highly selected group of patients.

PMID- 23164993
TI  - Somatostatin receptor scintigraphy in patients with metastatic uveal melanoma.
AB  - As uveal melanoma originates in the neural crest, we aimed to explore whether
      somatostatin receptor (SSTR) expression is present and plays any role in these
      patients. Heavily pretreated metastatic uveal melanoma patients were tested with
      somatostatin receptor scintigraphy (SRS). Planar images of the whole body
      complemented by single-photon emission computed tomography on suspected sites
      were acquired between 4 and 24 h after an intravenous administration of 185-222
      MBq (5-6 mCi) of indium-octeotride. SSTR expression in metastatic tissues was
      confirmed by immunohistochemistry. In seven patients, sandostatin LAR was used
      with therapeutic intention. Thirty white patients were tested. All had extensive
      metastatic disease and the median number of previous treatments was three. SRS
      was found to be positive in 14 (46%) of the patients, but was not related to sex,
      type of previous treatments, tumor site, or histological type. In 10 patients,
      sufficient tumor specimens were available to perform immunohistochemical staining
      for SSTR. All cases with positive SSTR-2A staining were also positive by SRS. Two
      of the seven patients who received sandostatin LAR died within a month after
      receiving the first dose, whereas another two (28.5%) had stable disease for more
      than 5 months. The median time to progression after starting sandostatin was 2.1
      months (range: 0.2-5.5 months). Approximately 50% of the uveal melanoma patients
      with extensive metastatic disease were positive for SSR, which was consistent
      with immunohistochemical staining for SSTR-2A. Therapeutic approaches targeting
      SSTR might be beneficial in patients with metastatic uveal melanoma.

PMID- 23164994
TI  - Fluorescence polarization-based assay using N-glycan-conjugated quantum dots for
      screening in hemagglutinin blockers for influenza A viruses.
AB  - Attachment of influenza virus to susceptible cells is mediated by viral protein
      hemagglutinin (HA), which recognizes cell surface glycoconjugates that terminate
      in alpha-sialosides. To develop anti-influenza drugs based on inhibition of HA
      mediated infection, novel fluorescent nanoparticles displaying multiple
      biantennary N-glycan chains with alpha-sialosides (A2-PC-QDs) that have high
      affinity for the HA were designed and constructed. The A2-PC-QDs enabled an easy
      and efficient fluorescence polarization (FP) assay for detection of interaction
      with the HA and competitive inhibition even by small molecule compounds against
      A2-PC-QDs-HA binding. The quantum dot (QD)-based FP assay established in the
      present study is a useful tool for high-throughput screening and to accelerate
      the development of novel and more effective blockers of the viral attachment of
      influenza virus.

PMID- 23164995
TI  - New methods for the concentration of viruses from urban sewage using quantitative
      PCR.
AB  - Viruses are among the most important pathogens present in water contaminated with
      feces or urine and represent a serious risk to human health. Four procedures for
      concentrating viruses from sewage have been compared in this work, three of which
      were developed in the present study. Viruses were quantified using PCR
      techniques. According to statistical analysis and the sensitivity to detect human
      adenoviruses (HAdV), JC polyomaviruses (JCPyV) and noroviruses genogroup II (NoV
      GGII): (i) a new procedure (elution and skimmed-milk flocculation procedure
      (ESMP)) based on the elution of the viruses with glycine-alkaline buffer followed
      by organic flocculation with skimmed-milk was found to be the most efficient
      method when compared to (ii) ultrafiltration and glycine-alkaline elution, (iii)
      a lyophilization-based method and (iv) ultracentrifugation and glycine-alkaline
      elution. Through the analysis of replicate sewage samples, ESMP showed
      reproducible results with a coefficient of variation (CV) of 16% for HAdV, 12%
      for JCPyV and 17% for NoV GGII. Using spiked samples, the viral recoveries were
      estimated at 30-95% for HAdV, 55-90% for JCPyV and 45-50% for NoV GGII. ESMP was
      validated in a field study using twelve 24-h composite sewage samples collected
      in an urban sewage treatment plant in the North of Spain that reported 100%
      positive samples with mean values of HAdV, JCPyV and NoV GGII similar to those
      observed in other studies. Although all of the methods compared in this work
      yield consistently high values of virus detection and recovery in urban sewage,
      some require expensive laboratory equipment. ESMP is an effective low-cost
      procedure which allows a large number of samples to be processed simultaneously
      and is easily standardizable for its performance in a routine laboratory working
      in water monitoring. Moreover, in the present study, a CV was applied and
      proposed as a parameter to evaluate and compare the methods for detecting viruses
      in sewage samples.

PMID- 23164996
TI  - Monoclonal antibodies against Caprine arthritis-encephalitis virus epitopes in
      the p28 and p55(gag) viral proteins.
AB  - The genome of the Caprine Arthritis-Encephalitis Virus (CAEV) encodes the
      polycistronic precursor protein p55(gag). Proteolytic cleavage of p55(gag)
      generates the viral core proteins. Some studies suggest that the CAEV p55(gag)
      protein contains epitopes or antigenic determinants for these core proteins. This
      work reinforces this hypothesis and demonstrates that monoclonal antibodies
      (MAbs) that are directed against the capsid protein (p28) of CAEV are also
      reactive against the precursor p55(gag) protein and the intermediate cleavage
      products, p44, p36 and p22. The major activity of the MAbs was directed against
      p28. The MAbF12 binding site in p28 was found to be a linear epitope with a
      structure that is stable after SDS treatment and remains unaltered after beta
      mercaptoethanol (beta-ME) treatment. The MAbF12 binding site in the p55(gag), p36
      and p22 proteins was found to be a linear epitope with cross-linked sulphide
      bonds. In conclusion, these findings suggest that the p28 epitope is presented
      differently from the epitope in the polycistronic precursor protein p55(gag). The
      highly immunogenic p28 contains a linear epitope that is detergent-stable and is
      not altered by beta-ME treatment, whereas the p55(gag) epitope contains a linear
      epitope susceptible to denaturing agents.

PMID- 23164997
TI  - Clinical evaluation of application of polyglycolic acid sheet and fibrin glue
      spray for partial glossectomy.
AB  - PURPOSE: The aim of this study was to evaluate the usefulness of covering open
      wounds with a polyglycolic acid (PGA) sheet and a fibrin glue spray after partial
      glossectomy. MATERIALS AND METHODS: We clinically evaluated postoperative pain
      and scar contracture in 44 patients who underwent partial glossectomy followed by
      covering with a PGA sheet and a fibrin glue spray (PGA sheet group), as compared
      with 29 patients who were closed primarily (primary closure group). RESULTS:
      Duration of nonsteroidal anti-inflammatory drugs was almost the same between the
      PGA sheet group and the primary closure group. The degree of scar contracture was
      mild in many cases in both groups. In the case in which the excision area was
      wide and depth was shallow, there was a tendency for the scar contracture to be
      less in the PGA sheet group. CONCLUSIONS: Our findings showed that the use of a
      PGA sheet and fibrin glue spray for open wounds resulting from partial
      glossectomy was useful in terms of rapid relief from postoperative pain and
      prevention of scar contracture.

PMID- 23164998
TI  - Mandibular reconstruction using computer-aided design and computer-aided
      manufacturing: an analysis of surgical results.
AB  - PURPOSE: The purpose of this study was to analyze the accuracy of virtual
      surgical planning in mandibular reconstruction. MATERIALS AND METHODS: This is a
      retrospective study involving 8 consecutive patients reconstructed with
      nonvascularized iliac crest bone grafts and free fibula osteomyocutaneous flaps.
      DICOM data from a maxillofacial skeleton computed tomography (CT) scan were sent
      to a medical modeling company and used to map the mandibular resection,
      anatomically place the mandibular reconstruction plate, and create surgical
      guides. After surgery a postoperative CT compared the virtual plan to the
      surgical result. Linear measurements [2 transverse and 1 anterior-posterior (A
      P)] were performed to determine if the virtual surgical result was achieved. The
      transverse measurements were made from the condylar head to condylar head and
      from the gonial angle to gonial angle. The A-P analysis was made by measuring a
      perpendicular line drawn from the anterior inferior mandibular border to the
      center point on the condylar head to condylar head measurement. RESULTS: The
      average surgical error in the A-P dimension for the iliac crest bone grafts and
      free fibula flap was 0.2 mm (range 0.0 mm to 0.7 mm) and 0.9 mm (range 0.2 mm to
      1.9 mm), respectively. In the transverse dimension the average surgical error was
      1.6 mm (range 0.7 mm to 2.4 mm) and 2.7 mm (range 1.9 mm to 4.5 mm) from condyle
      to condyle, and 1.7 mm (range 0.7 mm to 2.7 mm) and 2.5 mm (range 0.4 to 4.8 mm)
      from gonial angle to gonial angle. CONCLUSION: The use of CAD-CAM (Medical
      Modeling, Golden, Colorado) technology for the fabrication of surgical resection
      guides and mandibular reconstruction plates resulted in an accurate surgical
      result.

PMID- 23164999
TI  - Role of surface charge in cytotoxicity of charged manganese ferrite nanoparticles
      towards macrophages.
AB  - Amphiphilic surfactants have been used to disperse magnetic nanoparticles in
      biological media, because they exhibit a dual hydrophobic/hydrophilic affinity
      that facilitates the formation of a nanoemulsion, within which nanoparticle
      surfaces can be modified to achieve different physicochemical properties. For the
      investigation of the interactions of cells with charged magnetic nanoparticles in
      a biological medium, we selected the nanoemulsion method to prepare water-soluble
      magnetic nanoparticles using amphiphilic surfactant (polysorbate 80). The
      hydroxyl groups of polysorbate 80 were modified to carboxyl or amine groups. The
      chemical structures of carboxylated and aminated polysorbate 80 were confirmed,
      and water-soluble manganese ferrite nanoparticles (MFNPs) were synthesized with
      three types of polysorbate 80. Colloidal size, morphology, monodispersity,
      solubility and T2 relaxivity were found to be similar between the three types of
      MFNP. However, cationic MFNPs exhibited greater cytotoxicity in macrophages
      (RAW264.7 cells) and lower cellular membrane effective stiffness than anionic and
      non-ionic MFNPs. Moreover, cationic MFNPs exhibited large uptake efficiency for
      RAW264.7 cells compared with anionic or non-ionic MFNPs under the same
      conditions. Therefore, we propose that surface charge should be a key
      consideration factor in the design of magnetic nanoparticles for theragnostic
      applications.

PMID- 23165000
TI  - Composition and temperature-induced structural changes in lead-tellurite glasses
      on different length scales.
AB  - Processes occurring at macroscopic and microscopic length scales across the glass
      transition (T(g)) in lead-tellurite glass (PbO)(x)(TeO(2))(1-x) (x = 0.1-0.3) are
      investigated using Brillouin and Raman spectroscopy, respectively. For all the
      samples, the temperature dependence of the longitudinal acoustic (LA) mode is
      found to exhibit a universal scaling below T(g) and a rapid softening above T(g).
      The lower value of elastic modulus at a higher concentration of network modifier
      PbO, estimated from Brillouin data, arises due to loss of network rigidity. From
      quantitative analysis of the reduced Raman spectra, several modes are found to
      exhibit anomalous changes across T(g). Instead of the expected anharmonic
      behaviour, several modes exhibit hardening, suggesting stiffening of the
      stretching force constants with temperature, the effect being more pronounced in
      glasses with higher x. In addition, incorporation of PbO in the glass is also
      found to narrow down the bond-length distribution, as evident from the sharpening
      of the Raman bands. The stiffening of the force constants of molecular units at a
      microscopic length scale and the decrease of elastic constant attributed to loss
      of network rigidity on a macroscopic length scale appear to be opposite. These
      different behaviours at two length scales are understood on the basis of a
      microscopic model involving TeO(n) and PbO units in the structure.

PMID- 23165001
TI  - Inhibition of HIV-1 integrase dimerization and activity with crosslinked
      interfacial peptides.
AB  - Alternative modes of inhibition for the design of anti-HIV therapies are sought
      due to the resistance of HIV to a number of the currently approved drugs. A non
      active site strategy for generating potent inhibitors of HIV-1 integrase is
      described based on blocking protein association. Peptides alpha5 and alpha6
      derived from the HIV-1 integrase dimeric interface have previously demonstrated
      efficacious dimerization inhibition of HIV-1 integrase. Due to the proximity of
      the termini of these peptides within the integrase structure, a focused library
      of tethered agents was designed based on crosslinking the peptides alpha5 and
      alpha6 to mimic a larger interfacial region. The best crosslinked inhibitors are
      approximately five-fold more potent against HIV-1 integrase than the individual
      peptides alone or in combination. The most active agents have an inhibitory
      constant in the mid-nM range and function via a dissociative mechanism of
      inhibition.

PMID- 23165007
TI  - A dispermic chimera was identified in a healthy man with mixed field
      agglutination reaction in ABO blood grouping and mosaic 46, XY/46, XX karyotype.
AB  - BACKGROUND: Chimerism is the presence of two or more genetically distinct cell
      populations in one organism. Here, we reported the identification of dispermic
      chimerism in a 25-year-old male. METHODS: Blood grouping was performed with
      standard gel centrifugation test cards. ABO and HLA-A,-B,-C,-DRB1 and -DQB1 loci
      genotyping was determined with PCR sequence-based typing. A quantitative analysis
      of dual red cells populations was measured by flow cytometer. The karyotype was
      analyzed by G-banded chromosomes. Short tandem repeat (STR) analysis was
      performed on blood, buccal mucosal and hair shafts samples. RESULTS: A mixed
      field agglutination with anti-B antibody was observed with gel centrifugation
      tests, which showed a double populations of O and B groups RBCs. Two groups RBCs
      were also observed by flow cytometer with nearly 90% O group cells and 10% B
      group cells. The normal O01,O02,B101 alleles were identified in DNA sample of the
      proband. STR analysis revealed three alleles for
      D8S1179,D3S1358,TH01,D13S317,D16S539,D2S1338,D19S433,TPOX and D18S51 loci. HLA
      DRB1 and -DQB1 loci had three alleles and a karyotypic mosaic was found with 60%
      46, XY and 40% 46, XX karyotype in the proband. In all studies, the third allele
      was attributable to a dual paternal contribution. CONCLUSION: A individual with
      dispermic chimerism was identified, which would generate by fertilization of an
      oocyte and the corresponding second polar body by two different sperms.

PMID- 23165002
TI  - Thyroid nodules in pediatrics: which ones can be left alone, which ones must be
      investigated, when and how.
AB  - Thyroid nodules are less frequent in childhood than in adulthood, but are more
      often malignant. Recent estimates suggest that up to 25% of thyroid nodules in
      children are malignant, therefore, a more aggressive approach is recommended. In
      this review, we suggest an approach based on a first-step clinical, laboratory,
      and sonographic evaluation. A history of irradiation of the neck, cranium or
      upper thorax, previous thyroid diseases or thyroid neoplasms in the family should
      alert clinicians as being associated with a greater likelihood of malignant
      nodules. Signs or symptoms of hyperthyroidism and dysmorphic features should be
      carefully considered during the physical examination. Palpable firm lymph nodes,
      found in some 70% of cases, are the most significant clinical finding in children
      with malignant nodules. Although the routine determination of calcitonin levels
      is not uniformly practiced, it can help recognize sporadic or familial medullary
      thyroid neoplasms. Blood thyroid stimulating hormone, free thyroxine, and free
      triiodothyronine determinations (the latter in case of symptoms of
      hyperthyroidism) are aimed at identifying the few hyperthyroid patients, for whom
      the next step should be scintiscan. Hyperthyroid patients usually disclose an
      increased uptake, and a diagnosis of toxic adenoma is commonly made. Cases with
      normal thyroid function or hypothyroidism (which is usually subclinical) should
      be evaluated by fine-needle aspiration biopsy (FNAB). In eu/hypo-thyroid
      patients, scintiscan provides poor diagnostic information and should not be
      routinely employed. Thyroid ultrasonography is used to select cases for FNAB.
      Although ultrasound cannot reliably discriminate between benign and malignant
      lesions, it does provide an index of suspicion. Sonographic features that
      increase the likelihood of malignancy are microcalcifications, lymph node
      alterations, nodule growth under levothyroxine treatment, and increased
      intranodular vascularization demonstrated by color Doppler. There is growing
      evidence that elastography may provide further information on nodule
      characteristics. FNAB is indicated in all cases with a likelihood of malignancy.
      FNAB has a diagnostic accuracy of approximately 90% and is used in selection of
      patients which require surgery. Recently, histological markers and elastography
      have been introduced to increase the specificity of FNAB and ultrasound,
      respectively. The pitfall in FNAB cytology is the follicular cytology, in which
      it is not possible to distinguish between adenoma and carcinoma and therefore
      thyroidectomy is advised.

PMID- 23165008
TI  - The unexpected and facile molybdenum mediated formation of tri- and tetracyclic
      pentathiepins from pyrazine-alkynes and sulfur.
AB  - The synthesis of a novel family of pentathiepino-pyrrolo[1,2-a]pyrazine
      derivatives is reported. These compounds are formed by the reaction of alkynyl
      substituted heterocyclic precursors with elemental sulfur in the presence of
      molybdenum oxo bis-tetrasulfide under very mild conditions.

PMID- 23165009
TI  - A CO2-switchable polymer brush for reversible capture and release of proteins.
AB  - We report on a polymer brush that can be switched between extended (hydrated) and
      collapsed (dehydrated) chain conformational states just by passing CO(2) and an
      inert gas like N(2) in solution alternately. This conformational change allows
      for reversible adsorption and release of a protein. In contrast to adding acids
      and bases for pH change, using gases as the trigger makes it possible to repeat
      the switching cycle many times without salt accumulation.

PMID- 23165010
TI  - Calcium channels and migraine.
AB  - Missense mutations in CACNA1A, the gene that encodes the pore-forming alpha1
      subunit of human voltage-gated Ca(V)2.1 (P/Q-type) calcium channels, cause a rare
      form of migraine with aura (familial hemiplegic migraine type 1: FHM1). Migraine
      is a common disabling brain disorder whose key manifestations are recurrent
      attacks of unilateral headache that may be preceded by transient neurological
      aura symptoms. This review, first, briefly summarizes current understanding of
      the pathophysiological mechanisms that are believed to underlie migraine
      headache, migraine aura and the onset of a migraine attack, and briefly describes
      the localization and function of neuronal Ca(V)2.1 channels in the brain regions
      that have been implicated in migraine pathogenesis. Then, the review describes
      and discusses i) the functional consequences of FHM1 mutations on the biophysical
      properties of recombinant human Ca(V)2.1 channels and native Ca(V)2.1 channels in
      neurons of knockin mouse models carrying the mild R192Q or severe S218L mutations
      in the orthologous gene, and ii) the functional consequences of these mutations
      on neurophysiological processes in the cerebral cortex and trigeminovascular
      system thought to be involved in the pathophysiology of migraine, and the
      insights into migraine mechanisms obtained from the functional analysis of these
      processes in FHM1 knockin mice. This article is part of a Special Issue entitled:
      Calcium channels.

PMID- 23165012
TI  - Variable weighted ordered subset image reconstruction algorithm.
AB  - We propose two variable weighted iterative reconstruction algorithms (VW-ART and
      VW-OS-SART) to improve the algebraic reconstruction technique (ART) and
      simultaneous algebraic reconstruction technique (SART) and establish their
      convergence. In the two algorithms, the weighting varies with the geometrical
      direction of the ray. Experimental results with both numerical simulation and
      real CT data demonstrate that the VW-ART has a significant improvement in the
      quality of reconstructed images over ART and OS-SART. Moreover, both VW-ART and
      VW-OS-SART are more promising in convergence speed than the ART and SART,
      respectively.

PMID- 23165013
TI  - A general formula for fan-beam lambda tomography.
AB  - Lambda tomography (LT) is to reconstruct a gradient-like image of an object only
      from local projection data. It is potentially an important technology for medical
      X-ray computed tomography (CT) at a reduced radiation dose. In this paper, we
      prove the first general formula for exact and efficient fan-beam LT from data
      collected along any smooth curve based on even and odd data extensions. As a
      result, an LT image can be reconstructed without involving any data extension.
      This implies that structures outside a scanning trajectory do not affect the
      exact reconstruction of points inside the trajectory even if the data may be
      measured through the outside features. The algorithm is simulated in a collinear
      coordinate system. The results support our theoretical analysis.

PMID- 23165014
TI  - Mechanical strains induced in osteoblasts by use of point femtosecond laser
      targeting.
AB  - A study demonstrating how ultrafast laser radiation stimulates osteoblasts is
      presented. The study employed a custom made optical system that allowed for
      simultaneous confocal cell imaging and targeted femtosecond pulse laser
      irradiation. When femtosecond laser light was focused onto a single cell, a rise
      in intracellular Ca(2+) levels was observed followed by contraction of the
      targeted cell. This contraction caused deformation of neighbouring cells leading
      to a heterogeneous strain field throughout the monolayer. Quantification of the
      strain fields in the monolayer using digital image correlation revealed local
      strains much higher than threshold values typically reported to stimulate
      extracellular bone matrix production in vitro. This use of point targeting with
      femtosecond pulse lasers could provide a new method for stimulating cell activity
      in orthopaedic tissue engineering.

PMID- 23165015
TI  - BOLD Noise Assumptions in fMRI.
AB  - This paper discusses the assumption of Gaussian noise in the blood-oxygenation
      dependent (BOLD) contrast for functional MRI (fMRI). In principle, magnitudes in
      MRI images follow a Rice distribution. We start by reviewing differences between
      Rician and Gaussian noise. An analytic expression is derived for the null
      (resting-state) distribution of the difference between two Rician distributed
      images. This distribution is shown to be symmetric, and an exact expression for
      its standard deviation is derived. This distribution can be well approximated by
      a Gaussian, with very high precision for high SNR, and high precision for lower
      SNR. Tests on simulated and real MR images show that subtracting the time-series
      mean in fMRI yields asymmetrically distributed temporal noise. Subtracting a
      resting-state time series from the first results in symmetric and nearly Gaussian
      noise. This has important consequences for fMRI analyses using standard
      statistical tests.

PMID- 23165016
TI  - Probabilistic model-based cell tracking.
AB  - The study of cell behavior is of crucial importance in drug and disease research.
      The fields of bioinformatics and biotechnology rely on the collection,
      processing, and analysis of huge numbers of biocellular images, including cell
      features such as cell size, shape, and motility. However manual methods of
      inferring these values are so onerous that automated methods of cell tracking and
      segmentation are in high demand. In this paper, a novel model-based cell tracker
      is designed to locate and track individual cells. The proposed cell tracker has
      been successfully applied to track hematopoietic stem cells (HSCs) based on
      identified cell locations and probabilistic data association.

PMID- 23165017
TI  - Controlled cardiac computed tomography.
AB  - Cardiac computed tomography (CT) has been a hot topic for years because of the
      clinical importance of cardiac diseases and the rapid evolution of CT systems. In
      this paper, we propose a novel strategy for controlled cardiac CT that may
      effectively reduce image artifacts due to cardiac and respiratory motions. Our
      approach is radically different from existing ones and is based on controlling
      the X-ray source rotation velocity and powering status in reference to the
      cardiac motion. We theoretically show that by such a control-based intervention
      the data acquisition process can be optimized for cardiac CT in the cases of
      periodic and quasiperiodic cardiac motions. Specifically, we formulate the
      corresponding coordination/control schemes for either exact or approximate
      matches between the ideal and actual source positions, and report representative
      simulation results that support our analytic findings.

PMID- 23165018
TI  - Local ROI Reconstruction via Generalized FBP and BPF Algorithms along More
      Flexible Curves.
AB  - We study the local region-of-interest (ROI) reconstruction problem, also referred
      to as the local CT problem. Our scheme includes two steps: (a) the local
      truncated normal-dose projections are extended to global dataset by combining a
      few global low-dose projections; (b) the ROI are reconstructed by either the
      generalized filtered backprojection (FBP) or backprojection-filtration (BPF)
      algorithms. The simulation results show that both the FBP and BPF algorithms can
      reconstruct satisfactory results with image quality in the ROI comparable to that
      of the corresponding global CT reconstruction.

PMID- 23165019
TI  - Parallel Implementation of Katsevich's FBP Algorithm.
AB  - For spiral cone-beam CT, parallel computing is an effective approach to resolving
      the problem of heavy computation burden. It is well known that the major
      computation time is spent in the backprojection step for either filtered
      backprojection (FBP) or backprojected-filtration (BPF) algorithms. By the cone
      beam cover method [1], the backprojection procedure is driven by cone-beam
      projections, and every cone-beam projection can be backprojected independently.
      Basing on this fact, we develop a parallel implementation of Katsevich's FBP
      algorithm. We do all the numerical experiments on a Linux cluster. In one typical
      experiment, the sequential reconstruction time is 781.3 seconds, while the
      parallel reconstruction time is 25.7 seconds with 32 processors.

PMID- 23165020
TI  - The application of diffusion- and perfusion-weighted magnetic resonance imaging
      in the diagnosis and therapy of acute cerebral infarction.
AB  - Diffusion- and perfusion-weighted magnetic resonance imaging (DWI and PWI) was
      applied for stroke diagnose in 120 acute (< 48 h) ischemic stroke patients. At
      hyperacute (< 6 h) stage, it is difficult to find out the infarction zone in
      conventional T1 or T2 image, but it is easy in DWI, apparent diffusion
      coefficient (ADC) map; when at 3-6-hour stage it is also easy in PWI, cerebral
      blood flow (CBF) map, cerebral blood volume (CBV) map, and mean transit time
      (MTT) map; at acute (6-48 h) stage, DWI or PWI is more sensitive than
      conventional T1 or T2 image too. Combining DWI with ADC, acute and chronic
      infarction can be distinguished. Besides, penumbra which should be developed in
      meaning was used as an indication or to evaluate the therapeutic efficacy. There
      were two cases (< 1.5 h) that broke the model of penumbra because abnormity was
      found in DWI but not that in PWI, finally they recovered without any sequela.

PMID- 23165021
TI  - Intervention models in functional connectivity identification applied to FMRI.
AB  - Recent advances in neuroimaging techniques have provided precise spatial
      localization of brain activation applied in several neuroscience subareas. The
      development of functional magnetic resonance imaging (fMRI), based on the BOLD
      signal, is one of the most popular techniques related to the detection of
      neuronal activation. However, understanding the interactions between several
      neuronal modules is also an important task, providing a better comprehension
      about brain dynamics. Nevertheless, most connectivity studies in fMRI are based
      on a simple correlation analysis, which is only an association measure and does
      not provide the direction of information flow between brain areas. Other proposed
      methods like structural equation modeling (SEM) seem to be attractive
      alternatives. However, this approach assumes prior information about the
      causality direction and stationarity conditions, which may not be satisfied in
      fMRI experiments. Generally, the fMRI experiments are related to an activation
      task; hence, the stimulus conditions should also be included in the model. In
      this paper, we suggest an intervention analysis, which includes stimulus
      condition, allowing a nonstationary modeling. Furthermore, an illustrative
      application to real fMRI dataset from a simple motor task is presented.

PMID- 23165022
TI  - An Approximate Cone Beam Reconstruction Algorithm for Gantry-Tilted CT Using
      Tangential Filtering.
AB  - FDK algorithm is a well-known 3D (three-dimensional) approximate algorithm for CT
      (computed tomography) image reconstruction and is also known to suffer from
      considerable artifacts when the scanning cone angle is large. Recently, it has
      been improved by performing the ramp filtering along the tangential direction of
      the X-ray source helix for dealing with the large cone angle problem. In this
      paper, we present an FDK-type approximate reconstruction algorithm for gantry
      tilted CT imaging. The proposed method improves the image reconstruction by
      filtering the projection data along a proper direction which is determined by CT
      parameters and gantry-tilted angle. As a result, the proposed algorithm for
      gantry-tilted CT reconstruction can provide more scanning flexibilities in
      clinical CT scanning and is efficient in computation. The performance of the
      proposed algorithm is evaluated with turbell clock phantom and thorax phantom and
      compared with FDK algorithm and a popular 2D (two-dimensional) approximate
      algorithm. The results show that the proposed algorithm can achieve better image
      quality for gantry-tilted CT image reconstruction.

PMID- 23165023
TI  - Modeling and reconstruction of mixed functional and molecular patterns.
AB  - Functional medical imaging promises powerful tools for the visualization and
      elucidation of important disease-causing biological processes in living tissue.
      Recent research aims to dissect the distribution or expression of multiple
      biomarkers associated with disease progression or response, where the signals
      often represent a composite of more than one distinct source independent of
      spatial resolution. Formulating the task as a blind source separation or
      composite signal factorization problem, we report here a statistically principled
      method for modeling and reconstruction of mixed functional or molecular patterns.
      The computational algorithm is based on a latent variable model whose parameters
      are estimated using clustered component analysis. We demonstrate the principle
      and performance of the approaches on the breast cancer data sets acquired by
      dynamic contrast-enhanced magnetic resonance imaging.

PMID- 23165024
TI  - A prospective study on algorithms adapted to the spatial frequency in tomography.
AB  - The use of iterative algorithms in tomographic reconstruction always leads to a
      frequency adapted rate of convergence in that low frequencies are accurately
      reconstructed after a few iterations, while high frequencies sometimes require
      many more computations. In this paper, we propose to build frequency adapted (FA)
      algorithms based on a condition of incomplete backprojection and propose an FA
      simultaneous algebraic reconstruction technique (FA-SART) algorithm as an
      example. The results obtained with the FA-SART algorithm demonstrate a very fast
      convergence on a highly detailed phantom when compared to the original SART
      algorithm. Though the use of such an FA algorithm may seem difficult, we specify
      in which case it is relevant and propose several ways to improve the
      reconstruction process with FA algorithms.

PMID- 23165025
TI  - Optimization of spiral MRI using a perceptual difference model.
AB  - We systematically evaluated a variety of MR spiral imaging acquisition and
      reconstruction schemes using a computational perceptual difference model (PDM)
      that models the ability of humans to perceive a visual difference between a
      degraded "fast" MRI image with subsampling of k-space and a "gold standard" image
      mimicking full acquisition. Human subject experiments performed using a modified
      double-stimulus continuous-quality scale (DSCQS) correlated well with PDM, over a
      variety of images. In a smaller set of conditions, PDM scores agreed very well
      with human detectability measurements of image quality. Having validated the
      technique, PDM was used to systematically evaluate 2016 spiral image conditions
      (six interleave patterns, seven sampling densities, three density compensation
      schemes, four reconstruction methods, and four noise levels). Voronoi (VOR) with
      conventional regridding gave the best reconstructions. At a fixed sampling
      density, more interleaves gave better results. With noise present more
      interleaves and samples were desirable. With PDM, conditions were determined
      where equivalent image quality was obtained with 50% sampling in noise-free
      conditions. We conclude that PDM scoring provides an objective, useful tool for
      the assessment of fast MR image quality that can greatly aid the design of MR
      acquisition and signal processing strategies.

PMID- 23165026
TI  - Increased depth of cellular imaging in the intact lung using far-red and near
      infrared fluorescent probes.
AB  - Scattering of shorter-wavelength visible light limits the fluorescence imaging
      depth of thick specimens such as whole organs. In this study, we report the use
      of four newly synthesized near-infrared and far-red fluorescence probes
      (excitation/emission, in nm: 644/670; 683/707; 786/814; 824/834) to image tumor
      cells in the subpleural vasculature of the intact rat lungs. Transpelural imaging
      of tumor cells labeled with long-wavelength probes and expressing green
      fluorescent protein (GFP; excitation/emission 488/507 nm) was done in the intact
      rat lung after perfusate administration or intravenous injection. Our results
      show that the average optimum imaging depth for the long-wavelength probes is
      higher (27.8 +/- 0.7  MUm) than for GFP (20 +/- 0.5  MUm; p = 0.008; n = 50),
      corresponding to a 40% increase in the volume of tissue accessible for high
      resolution imaging. The maximum depth of cell visualization was significantly
      improved with the novel dyes (36.4 +/- 1  MUm from the pleural surface) compared
      with GFP (30.1 +/- 0.5  MUm; p = 0.01; n = 50). Stable binding of the long
      wavelength vital dyes to the plasma membrane also permitted in vivo tracking of
      injected tumor cells in the pulmonary vasculature. These probes offer a
      significant improvement in the imaging quality of in situ biological processes in
      the deeper regions of intact lungs.

PMID- 23165027
TI  - Assessment of Left Ventricular Function in Cardiac MSCT Imaging by a 4D
      Hierarchical Surface-Volume Matching Process.
AB  - Multislice computed tomography (MSCT) scanners offer new perspectives for cardiac
      kinetics evaluation with 4D dynamic sequences of high contrast and spatiotemporal
      resolutions. A new method is proposed for cardiac motion extraction in multislice
      CT. Based on a 4D hierarchical surface-volume matching process, it provides the
      detection of the heart left cavities along the acquired sequence and the
      estimation of their 3D surface velocity fields. A Markov random field model is
      defined to find, according to topological descriptors, the best correspondences
      between a 3D mesh describing the left endocardium at one time and the 3D acquired
      volume at the following time. The global optimization of the correspondences is
      realized with a multiresolution process. Results obtained on simulated and real
      data show the capabilities to extract clinically relevant global and local motion
      parameters and highlight new perspectives in cardiac computed tomography imaging.

PMID- 23165028
TI  - Development of computed tomography algorithms.

PMID- 23165029
TI  - Comparison of quadratic- and median-based roughness penalties for penalized
      likelihood sinogram restoration in computed tomography.
AB  - We have compared the performance of two different penalty choices for a penalized
      likelihood sinogram-restoration strategy we have been developing. One is a
      quadratic penalty we have employed previously and the other is a new median-based
      penalty. We compared the approaches to a noniterative adaptive filter that
      loosely but not explicitly models data statistics. We found that the two
      approaches produced similar resolution-variance tradeoffs to each other and that
      they outperformed the adaptive filter in the low-dose regime, which suggests that
      the particular choice of penalty in our approach may be less important than the
      fact that we are explicitly modeling data statistics at all. Since the quadratic
      penalty allows for derivation of an algorithm that is guaranteed to monotonically
      increase the penalized-likelihood objective function, we find it to be preferable
      to the median-based penalty.

PMID- 23165030
TI  - A decision support framework for automated screening of diabetic retinopathy.
AB  - The early signs of diabetic retinopathy (DR) are depicted by microaneurysms among
      other signs. A prompt diagnosis when the disease is at the early stage can help
      prevent irreversible damages to the diabetic eye. In this paper, we propose a
      decision support system (DSS) for automated screening of early signs of diabetic
      retinopathy. Classification schemes for deducing the presence or absence of DR
      are developed and tested. The detection rule is based on binary-hypothesis
      testing problem which simplifies the problem to yes/no decisions. An analysis of
      the performance of the Bayes optimality criteria applied to DR is also presented.
      The proposed DSS is evaluated on the real-world data. The results suggest that by
      biasing the classifier towards DR detection, it is possible to make the
      classifier achieve good sensitivity.

PMID- 23165031
TI  - Extending Three-Dimensional Weighted Cone Beam Filtered Backprojection (CB-FBP)
      Algorithm for Image Reconstruction in Volumetric CT at Low Helical Pitches.
AB  - A three-dimensional (3D) weighted helical cone beam filtered backprojection (CB
      FBP) algorithm (namely, original 3D weighted helical CB-FBP algorithm) has
      already been proposed to reconstruct images from the projection data acquired
      along a helical trajectory in angular ranges up to [0, 2 pi]. However, an
      overscan is usually employed in the clinic to reconstruct tomographic images with
      superior noise characteristics at the most challenging anatomic structures, such
      as head and spine, extremity imaging, and CT angiography as well. To obtain the
      most achievable noise characteristics or dose efficiency in a helical overscan,
      we extended the 3D weighted helical CB-FBP algorithm to handle helical pitches
      that are smaller than 1: 1 (namely extended 3D weighted helical CB-FBP
      algorithm). By decomposing a helical over scan with an angular range of [0, 2pi +
      Deltabeta] into a union of full scans corresponding to an angular range of [0,
      2pi], the extended 3D weighted function is a summation of all 3D weighting
      functions corresponding to each full scan. An experimental evaluation shows that
      the extended 3D weighted helical CB-FBP algorithm can improve noise
      characteristics or dose efficiency of the 3D weighted helical CB-FBP algorithm at
      a helical pitch smaller than 1: 1, while its reconstruction accuracy and
      computational efficiency are maintained. It is believed that, such an efficient
      CB reconstruction algorithm that can provide superior noise characteristics or
      dose efficiency at low helical pitches may find its extensive applications in CT
      medical imaging.

PMID- 23165032
TI  - Anisotropic elastography for local passive properties and active contractility of
      myocardium from dynamic heart imaging sequence.
AB  - Major heart diseases such as ischemia and hypertrophic myocardiopathy are
      accompanied with significant changes in the passive mechanical properties and
      active contractility of myocardium. Identification of these changes helps
      diagnose heart diseases, monitor therapy, and design surgery. A dynamic cardiac
      elastography (DCE) framework is developed to assess the anisotropic viscoelastic
      passive properties and active contractility of myocardial tissues, based on the
      chamber pressure and dynamic displacement measured with cardiac imaging
      techniques. A dynamic adjoint method is derived to enhance the numerical
      efficiency and stability of DCE. Model-based simulations are conducted using a
      numerical left ventricle (LV) phantom with an ischemic region. The passive
      material parameters of normal and ischemic tissues are identified during LV
      rapid/reduced filling and artery contraction, and those of active contractility
      are quantified during isovolumetric contraction and rapid/reduced ejection. It is
      found that quasistatic simplification in the previous cardiac elastography
      studies may yield inaccurate material parameters.

PMID- 23165033
TI  - An Optimized Spline-Based Registration of a 3D CT to a Set of C-Arm Images.
AB  - We have developed an algorithm for the rigid-body registration of a CT volume to
      a set of C-arm images. The algorithm uses a gradient-based iterative minimization
      of a least-squares measure of dissimilarity between the C-arm images and
      projections of the CT volume. To compute projections, we use a novel method for
      fast integration of the volume along rays. To improve robustness and speed, we
      take advantage of a coarse-to-fine processing of the volume/image pyramids. To
      compute the projections of the volume, the gradient of the dissimilarity measure,
      and the multiresolution data pyramids, we use a continuous image/volume model
      based on cubic B-splines, which ensures a high interpolation accuracy and a
      gradient of the dissimilarity measure that is well defined everywhere. We show
      the performance of our algorithm on a human spine phantom, where the true
      alignment is determined using a set of fiducial markers.

PMID- 23165034
TI  - Progressive magnetic resonance image reconstruction based on iterative solution
      of a sparse linear system.
AB  - Image reconstruction from nonuniformly sampled spatial frequency domain data is
      an important problem that arises in computed imaging. Current reconstruction
      techniques suffer from limitations in their model and implementation. In this
      paper, we present a new reconstruction method that is based on solving a system
      of linear equations using an efficient iterative approach. Image pixel
      intensities are related to the measured frequency domain data through a set of
      linear equations. Although the system matrix is too dense and large to solve by
      direct inversion in practice, a simple orthogonal transformation to the rows of
      this matrix is applied to convert the matrix into a sparse one up to a certain
      chosen level of energy preservation. The transformed system is subsequently
      solved using the conjugate gradient method. This method is applied to reconstruct
      images of a numerical phantom as well as magnetic resonance images from
      experimental spiral imaging data. The results support the theory and demonstrate
      that the computational load of this method is similar to that of standard
      gridding, illustrating its practical utility.

PMID- 23165035
TI  - A Review on MR Image Intensity Inhomogeneity Correction.
AB  - Intensity inhomogeneity (IIH) is often encountered in MR imaging, and a number of
      techniques have been devised to correct this artifact. This paper attempts to
      review some of the recent developments in the mathematical modeling of IIH field.
      Low-frequency models are widely used, but they tend to corrupt the low-frequency
      components of the tissue. Hypersurface models and statistical models can be
      adaptive to the image and generally more stable, but they are also generally more
      complex and consume more computer memory and CPU time. They are often formulated
      together with image segmentation within one framework and the overall performance
      is highly dependent on the segmentation process. Beside these three popular
      models, this paper also summarizes other techniques based on different
      principles. In addition, the issue of quantitative evaluation and comparative
      study are discussed.

PMID- 23165036
TI  - Elasto-mammography: Theory, Algorithm, and Phantom Study.
AB  - A new imaging modality framework, called elasto-mammography, is proposed to
      generate the elastograms of breast tissues based on conventional X-ray
      mammography. The displacement information is extracted from mammography
      projections before and after breast compression. Incorporating the displacement
      measurement, an elastography reconstruction algorithm is specifically developed
      to estimate the elastic moduli of heterogeneous breast tissues. Case studies with
      numerical breast phantoms are conducted to demonstrate the capability of the
      proposed elasto-mammography. Effects of noise with measurement, geometric
      mismatch, and elastic contrast ratio are evaluated in the numerical simulations.
      It is shown that the proposed methodology is stable and robust for
      characterization of the elastic moduli of breast tissues from the projective
      displacement measurement.

PMID- 23165037
TI  - 3D Brain Segmentation Using Dual-Front Active Contours with Optional User
      Interaction.
AB  - Important attributes of 3D brain cortex segmentation algorithms include
      robustness, accuracy, computational efficiency, and facilitation of user
      interaction, yet few algorithms incorporate all of these traits. Manual
      segmentation is highly accurate but tedious and laborious. Most automatic
      techniques, while less demanding on the user, are much less accurate. It would be
      useful to employ a fast automatic segmentation procedure to do most of the work
      but still allow an expert user to interactively guide the segmentation to ensure
      an accurate final result. We propose a novel 3D brain cortex segmentation
      procedure utilizing dual-front active contours which minimize image-based
      energies in a manner that yields flexibly global minimizers based on active
      regions. Region-based information and boundary-based information may be combined
      flexibly in the evolution potentials for accurate segmentation results. The
      resulting scheme is not only more robust but much faster and allows the user to
      guide the final segmentation through simple mouse clicks which add extra seed
      points. Due to the flexibly global nature of the dual-front evolution model,
      single mouse clicks yield corrections to the segmentation that extend far beyond
      their initial locations, thus minimizing the user effort. Results on 15 simulated
      and 20 real 3D brain images demonstrate the robustness, accuracy, and speed of
      our scheme compared with other methods.

PMID- 23165038
TI  - Mathematical study and numerical simulation of multispectral bioluminescence
      tomography.
AB  - Multispectral bioluminescence tomography (BLT) attracts increasingly more
      attention in the area of optical molecular imaging. In this paper, we analyze the
      properties of the solutions to the regularized and discretized multispectral BLT
      problems. First, we show the solution existence, uniqueness, and its continuous
      dependence on the data. Then, we introduce stable numerical schemes and derive
      error estimates for numerical solutions. We report some numerical results to
      illustrate the performance of the numerical methods on the quality of
      multispectral BLT reconstruction.

PMID- 23165039
TI  - A hybrid approach of using wavelets and fuzzy clustering for classifying
      multispectral florescence in situ hybridization images.
AB  - Multicolor or multiplex fluorescence in situ hybridization (M-FISH) imaging is a
      recently developed molecular cytogenetic diagnosis technique for rapid
      visualization of genomic aberrations at the chromosomal level. By the
      simultaneous use of all 24 human chromosome painting probes, M-FISH imaging
      facilitates precise identification of complex chromosomal rearrangements that are
      responsible for cancers and genetic diseases. The current approaches, however,
      cannot have the precision sufficient for clinical use. The reliability of the
      technique depends primarily on the accurate pixel-wise classification, that is,
      assigning each pixel into one of the 24 classes of chromosomes based on its six
      channel spectral representations. In the paper we introduce a novel approach to
      improve the accuracy of pixel-wise classification. The approach is based on the
      combination of fuzzy clustering and wavelet normalization. Two wavelet-based
      algorithms are used to reduce redundancies and to correct misalignments between
      multichannel FISH images. In comparison with conventional algorithms, the wavelet
      based approaches offer more advantages such as the adaptive feature selection and
      accurate image registration. The algorithms have been tested on images from
      normal cells, showing the improvement in classification accuracy. The increased
      accuracy of pixel-wise classification will improve the reliability of the M-FISH
      imaging technique in identifying subtle and cryptic chromosomal abnormalities for
      cancer diagnosis and genetic disorder research.

PMID- 23165040
TI  - Multispectral bioluminescence tomography: methodology and simulation.
AB  - Bioluminescent imaging has proven to be a valuable tool for monitoring
      physiological and pathological activities at cellular and molecular levels in
      living small animals. Using biological techniques, target cells can be tagged
      with reporters encoding several kinds of luciferase enzymes, which generate
      characteristic photons in a wide spectrum covering the infrared range. Part of
      the diffused light can reach the body surface of the small animal, be separated
      into several spectral bands using appropriate filters, and collected by a
      sensitive CCD camera. Here we present a bioluminescence tomography (BLT) method
      for a bioluminescent source reconstruction from multispectral data measured on
      the external surface, and demonstrate the advantages of multispectral BLT in a
      numerical study using a heterogeneous mouse chest phantom. The results show that
      the multispectral approach significantly improves the accuracy and stability of
      the BLT reconstruction even if the data are highly noisy.

PMID- 23165041
TI  - Unsupervised Detection of Suspicious Tissue Using Data Modeling and PCA.
AB  - Breast cancer is a major cause of death and morbidity among women all over the
      world, and it is a fact that early detection is a key in improving outcomes.
      Therefore development of algorithms that aids radiologists in identifying changes
      in breast tissue early on is essential. In this work an algorithm that
      investigates the use of principal components analysis (PCA) is developed to
      identify suspicious regions on mammograms. The algorithm employs linear structure
      and curvelinear modeling prior to PCA implementations. Evaluation of the
      algorithm is based on the percentage of correct classification, false positive
      (FP) and false negative (FN) in all experimental work using real data. Over 90%
      accuracy in block classification is achieved using mammograms from MIAS database.

PMID- 23165042
TI  - The first bioluminescence tomography system for simultaneous acquisition of
      multiview and multispectral data.
AB  - We describe the system design of the first bioluminescence tomography (BLT)
      system for parallel acquisition of multiple bioluminescent views around a mouse
      in a number of spectral channels simultaneously. The primary component of this
      BLT system is a novel mirror module and a unique mouse holder. The mirror module
      consists of a mounting plate and four mirrors with stages. These mirror stages
      are right triangular blocks symmetrically arranged and attached to the mounting
      plate such that the hypotenuse surfaces of the triangular blocks all make 45(?)
      to the plate surface. The cylindrical/polygonal mouse holder has semitransparent
      rainbow bands on its side surface for the acquisition of spectrally resolved
      data. Numerical studies and experiments are performed to demonstrate the
      feasibility of this system. It is shown that bioluminescent signals collected
      using our system can produce a similar BLT reconstruction quality while reducing
      the data acquisition time, as compared to the sequential data acquisition mode.

PMID- 23165043
TI  - Automated analysis of fluorescence microscopy images to identify protein-protein
      interactions.
AB  - The identification of protein interactions is important for elucidating
      biological networks. One obstacle in comprehensive interaction studies is the
      analyses of large datasets, particularly those containing images. Development of
      an automated system to analyze an image-based protein interaction dataset is
      needed. Such an analysis system is described here, to automatically extract
      features from fluorescence microscopy images obtained from a bacterial protein
      interaction assay. These features are used to relay quantitative values that aid
      in the automated scoring of positive interactions. Experimental observations
      indicate that identifying at least 50% positive cells in an image is sufficient
      to detect a protein interaction. Based on this criterion, the automated system
      presents 100% accuracy in detecting positive interactions for a dataset of 16
      images. Algorithms were implemented using MATLAB and the software developed is
      available on request from the authors.

PMID- 23165044
TI  - Recent advances in mathematical methods for the analysis of biomedical image.

PMID- 23165045
TI  - A parallel reconstruction scheme in fluorescence tomography based on contrast of
      independent inversed absorption properties.
AB  - Based on an independent forward model in fluorescent tomography, a parallel
      reconstructed scheme for inhomogeneous mediums with unknown absorption property
      is proposed in this paper. The method considers the two diffusion equations as
      separately describing the propagation of excited light in tissues with and
      without fluorescent probes inside. Then the concentration of fluorophores is
      obtained directly through the difference between two estimations of absorption
      coefficient which can be parallel inversed. In this way, the multiparameter
      estimation problem in fluorescent tomography is transformed into two independent
      single-coefficient determined schemes of diffusion optical tomography (DOT). Any
      algorithms proved to be efficient and effective in DOT can be directly applied
      here. In this study the absorption property is estimated from the independent
      diffusion equations by a gradient-based optimization method with finite element
      method (FEM) solving the forward model. Simulation results of three
      representative occasions show that the reconstructed method can well estimate
      fluorescent property and tissue absorption distribution.

PMID- 23165046
TI  - Nonrigid medical image registration by finite-element deformable sheet-curve
      models.
AB  - Image-based change quantitation has been recognized as a promising tool for
      accurate assessment of tumor's early response to chemoprevention in cancer
      research. For example, various changes on breast density and vascularity in
      glandular tissue are the indicators of early response to treatment. Accurate
      extraction of glandular tissue from pre- and postcontrast magnetic resonance (MR)
      images requires a nonrigid registration of sequential MR images embedded with
      local deformations. This paper reports a newly developed registration method that
      aligns MR breast images using finite-element deformable sheet-curve models.
      Specifically, deformable curves are constructed to match the boundaries
      dynamically, while a deformable sheet of thin-plate splines is designed to model
      complex local deformations. The experimental results on both digital phantoms and
      real MR breast images using the new method have been compared to point-based thin
      plate-spline (TPS) approach, and have demonstrated a significant and robust
      improvement in both boundary alignment and local deformation recovery.

PMID- 23165047
TI  - Reciprocal Benefits of Mass-Univariate and Multivariate Modeling in Brain
      Mapping: Applications to Event-Related Functional MRI, H(2) (15)O-, and FDG-PET.
AB  - In brain mapping studies of sensory, cognitive, and motor operations, specific
      waveforms of dynamic neural activity are predicted based on theoretical models of
      human information processing. For example in event-related functional MRI (fMRI),
      the general linear model (GLM) is employed in mass-univariate analyses to
      identify the regions whose dynamic activity closely matches the expected
      waveforms. By comparison multivariate analyses based on PCA or ICA provide
      greater flexibility in detecting spatiotemporal properties of experimental data
      that may strongly support alternative neuroscientific explanations. We
      investigated conjoint multivariate and mass-univariate analyses that combine the
      capabilities to (1) verify activation of neural machinery we already understand
      and (2) discover reliable signatures of new neural machinery. We examined
      combinations of GLM and PCA that recover latent neural signals (waveforms and
      footprints) with greater accuracy than either method alone. Comparative results
      are illustrated with analyses of real fMRI data, adding to Monte Carlo simulation
      support.

PMID- 23165048
TI  - Analysis of Cone-Beam Artifacts in off-Centered Circular CT for Four
      Reconstruction Methods.
AB  - Cone-beam (CB) acquisition is increasingly used for truly three-dimensional X-ray
      computerized tomography (CT). However, tomographic reconstruction from data
      collected along a circular trajectory with the popular Feldkamp algorithm is
      known to produce the so-called CB artifacts. These artifacts result from the
      incompleteness of the source trajectory and the resulting missing data in the
      Radon space increasing with the distance to the plane containing the source
      orbit. In the context of the development of integrated PET/CT microscanners, we
      introduced a novel off-centered circular CT cone-beam geometry. We proposed a
      generalized Feldkamp formula (alpha-FDK) adapted to this geometry, but
      reconstructions suffer from increased CB artifacts. In this paper, we evaluate
      and compare four different reconstruction methods for correcting CB artifacts in
      off-centered geometry. We consider the alpha-FDK algorithm, the shift-variant FBP
      method derived from the T-FDK, an FBP method based on the Grangeat formula, and
      an iterative algebraic method (SART). The results show that the low contrast
      artifacts can be efficiently corrected by the shift-variant method and the SART
      method to achieve good quality images at the expense of increased computation
      time, but the geometrical deformations are still not compensated for by these
      techniques.

PMID- 23165049
TI  - Message from the Editor-in-Chief.

PMID- 23165050
TI  - A table-based random sampling simulation for bioluminescence tomography.
AB  - As a popular simulation of photon propagation in turbid media, the main problem
      of Monte Carlo (MC) method is its cumbersome computation. In this work a table
      based random sampling simulation (TBRS) is proposed. The key idea of TBRS is to
      simplify multisteps of scattering to a single-step process, through randomly
      table querying, thus greatly reducing the computing complexity of the
      conventional MC algorithm and expediting the computation. The TBRS simulation is
      a fast algorithm of the conventional MC simulation of photon propagation. It
      retained the merits of flexibility and accuracy of conventional MC method and
      adapted well to complex geometric media and various source shapes. Both MC
      simulations were conducted in a homogeneous medium in our work. Also, we present
      a reconstructing approach to estimate the position of the fluorescent source
      based on the trial-and-error theory as a validation of the TBRS algorithm. Good
      agreement is found between the conventional MC simulation and the TBRS
      simulation.

PMID- 23165051
TI  - Evolution-operator-based single-step method for image processing.
AB  - This work proposes an evolution-operator-based single-time-step method for image
      and signal processing. The key component of the proposed method is a local
      spectral evolution kernel (LSEK) that analytically integrates a class of
      evolution partial differential equations (PDEs). From the point of view PDEs, the
      LSEK provides the analytical solution in a single time step, and is of spectral
      accuracy, free of instability constraint. From the point of image/signal
      processing, the LSEK gives rise to a family of lowpass filters. These filters
      contain controllable time delay and amplitude scaling. The new evolution operator
      based method is constructed by pointwise adaptation of anisotropy to the
      coefficients of the LSEK. The Perona-Malik-type of anisotropic diffusion schemes
      is incorporated in the LSEK for image denoising. A forward-backward diffusion
      process is adopted to the LSEK for image deblurring or sharpening. A coupled PDE
      system is modified for image edge detection. The resulting image edge is utilized
      for image enhancement. Extensive computer experiments are carried out to
      demonstrate the performance of the proposed method. The major advantages of the
      proposed method are its single-step solution and readiness for multidimensional
      data analysis.

PMID- 23165052
TI  - FDK Half-Scan with a Heuristic Weighting Scheme on a Flat Panel Detector-Based
      Cone Beam CT (FDKHSCW).
AB  - A cone beam circular half-scan scheme is becoming an attractive imaging method in
      cone beam CT since it improves the temporal resolution. Traditionally, the
      redundant data in the circular half-scan range is weighted by a central scanning
      plane-dependent weighting function; FDK algorithm is then applied on the weighted
      projection data for reconstruction. However, this scheme still suffers the
      attenuation coefficient drop inherited with FDK when the cone angle becomes
      large. A new heuristic cone beam geometry-dependent weighting scheme is proposed
      based on the idea that there exists less redundancy for the projection data away
      from the central scanning plane. The performance of FDKHSCW scheme is evaluated
      by comparing it to the FDK full-scan (FDKFS) scheme and the traditional FDK half
      scan scheme with Parker's fan beam weighting function (FDKHSFW). Computer
      simulation is employed and conducted on a 3D Shepp-Logan phantom. The result
      illustrates a correction of FDKHSCW to the attenuation coefficient drop in the
      off-scanning plane associated with FDKFS and FDKHSFW while maintaining the same
      spatial resolution.

PMID- 23165053
TI  - Brain structure segmentation from MRI by geometric surface flow.
AB  - We present a method for semiautomatic segmentation of brain structures such as
      thalamus from MRI images based on the concept of geometric surface flow. Given an
      MRI image, the user can interactively initialize a seed model within region of
      interest. The model will then start to evolve by incorporating both boundary and
      region information following the principle of variational analysis. The
      deformation will stop when an equilibrium state is achieved. To overcome the low
      contrast of the original image data, a nonparametric kernel-based method is
      applied to simultaneously update the interior probability distribution during the
      model evolution. Our experiments on both 2D and 3D image data demonstrate that
      the new method is robust to image noise and inhomogeneity and will not leak from
      spurious edge gaps.

PMID- 23165054
TI  - Improving Non-Cartesian MRI Reconstruction through Discontinuity Subtraction.
AB  - Non-Cartesian sampling is widely used for fast magnetic resonance imaging (MRI).
      Accurate and fast image reconstruction from non-Cartesian k-space data becomes a
      challenge and gains a lot of attention. Images provided by conventional direct
      reconstruction methods usually bear ringing, streaking, and other leakage
      artifacts caused by discontinuous structures. In this paper, we tackle these
      problems by analyzing the principal point spread function (PSF) of non-Cartesian
      reconstruction and propose a leakage reduction reconstruction scheme based on
      discontinuity subtraction. Data fidelity in k-space is enforced during each
      iteration. Multidimensional nonuniform fast Fourier transform (NUFFT) algorithms
      are utilized to simulate the k-space samples as well as to reconstruct images.
      The proposed method is compared to the direct reconstruction method on computer
      simulated phantoms and physical scans. Non-Cartesian sampling trajectories
      including 2D spiral, 2D and 3D radial trajectories are studied. The proposed
      method is found useful on reducing artifacts due to high image discontinuities.
      It also improves the quality of images reconstructed from undersampled data.

PMID- 23165055
TI  - A Multiresolution PDE-Based Deformable Surface for Medical Imaging Applications.
AB  - We recently developed a multiresolution PDE-based deformable surface whose
      deformation behavior is governed by partial differential equations (PDEs) such as
      the weighted minimal surface flow. Comparing with the level-set approach, our new
      model has better control of the mesh quality and model resolution, and is much
      simpler to implement since all the computations are local. The new deformable
      model is very useful for a variety of medical imaging applications including
      boundary reconstruction, surface visualization, data segmentation, and topology
      discovery. In this paper, we demonstrate both the accuracy and robustness of our
      model on areas such as medical image segmentation through a number of experiments
      on both real (MRI/CT) and synthetic volumetric datasets.

PMID- 23165056
TI  - Comparison of Lesion Detection and Quantification in MAP Reconstruction with
      Gaussian and Non-Gaussian Priors.
AB  - Statistical image reconstruction methods based on maximum a posteriori (MAP)
      principle have been developed for emission tomography. The prior distribution of
      the unknown image plays an important role in MAP reconstruction. The most
      commonly used prior are Gaussian priors, whose logarithm has a quadratic form.
      Gaussian priors are relatively easy to analyze. It has been shown that the effect
      of a Gaussian prior can be approximated by linear filtering a maximum likelihood
      (ML) reconstruction. As a result, sharp edges in reconstructed images are not
      preserved. To preserve sharp transitions, non-Gaussian priors have been proposed.
      However, their effect on clinical tasks is less obvious. In this paper, we
      compare MAP reconstruction with Gaussian and non-Gaussian priors for lesion
      detection and region of interest quantification using computer simulation. We
      evaluate three representative priors: Gaussian prior, Huber prior, and Geman
      McClure prior. We simulate imaging a prostate tumor using positron emission
      tomography (PET). The detectability of a known tumor in either a fixed background
      or a random background is measured using a channelized Hotelling observer. The
      bias-variance tradeoff curves are calculated for quantification of the total
      tumor activity. The results show that for the detection and quantification tasks,
      the Gaussian prior is as effective as non-Gaussian priors.

PMID- 23165057
TI  - Total variation wavelet-based medical image denoising.
AB  - We propose a denoising algorithm for medical images based on a combination of the
      total variation minimization scheme and the wavelet scheme. We show that our
      scheme offers effective noise removal in real noisy medical images while
      maintaining sharpness of objects. More importantly, this scheme allows us to
      implement an effective automatic stopping time criterion.

PMID- 23165058
TI  - Partial volume reduction by interpolation with reverse diffusion.
AB  - Many medical images suffer from the partial volume effect where a boundary
      between two structures of interest falls in the midst of a voxel giving a signal
      value that is a mixture of the two. We propose a method to restore the ideal
      boundary by splitting a voxel into subvoxels and reapportioning the signal into
      the subvoxels. Each voxel is divided by nearest neighbor interpolation. The gray
      level of each subvoxel is considered as "material" able to move between subvoxels
      but not between voxels. A partial differential equation is written to allow the
      material to flow towards the highest gradient direction, creating a "reverse"
      diffusion process. Flow is subject to constraints that tend to create step edges.
      Material is conserved in the process thereby conserving signal. The method
      proceeds until the flow decreases to a low value. To test the method, synthetic
      images were downsampled to simulate the partial volume artifact and restored.
      Corrected images were remarkably closer both visually and quantitatively to the
      original images than those obtained from common interpolation methods: on
      simulated data standard deviation of the errors were 3.8%, 6.6%, and 7.1% of the
      dynamic range for the proposed method, bicubic, and bilinear interpolation,
      respectively. The method was relatively insensitive to noise. On gray level,
      scanned text, MRI physical phantom, and brain images, restored images processed
      with the new method were visually much closer to high-resolution counterparts
      than those obtained with common interpolation methods.

PMID- 23165059
TI  - A stochastic-variational model for soft mumford-shah segmentation.
AB  - In contemporary image and vision analysis, stochastic approaches demonstrate
      great flexibility in representing and modeling complex phenomena, while
      variational-PDE methods gain enormous computational advantages over Monte Carlo
      or other stochastic algorithms. In combination, the two can lead to much more
      powerful novel models and efficient algorithms. In the current work, we propose a
      stochastic-variational model for soft (or fuzzy) Mumford-Shah segmentation of
      mixture image patterns. Unlike the classical hard Mumford-Shah segmentation, the
      new model allows each pixel to belong to each image pattern with some
      probability. Soft segmentation could lead to hard segmentation, and hence is more
      general. The modeling procedure, mathematical analysis on the existence of
      optimal solutions, and computational implementation of the new model are explored
      in detail, and numerical examples of both synthetic and natural images are
      presented.

PMID- 23165060
TI  - Complete sets of radiating and nonradiating parts of a source and their fields
      with applications in inverse scattering limited-angle problems.
AB  - Many algorithms applied in inverse scattering problems use source-field systems
      instead of the direct computation of the unknown scatterer. It is well known that
      the resulting source problem does not have a unique solution, since certain parts
      of the source totally vanish outside of the reconstruction area. This paper
      provides for the two-dimensional case special sets of functions, which include
      all radiating and all nonradiating parts of the source. These sets are used to
      solve an acoustic inverse problem in two steps. The problem under discussion
      consists of determining an inhomogeneous obstacle supported in a part of a disc,
      from data, known for a subset of a two-dimensional circle. In a first step, the
      radiating parts are computed by solving a linear problem. The second step is
      nonlinear and consists of determining the nonradiating parts.

PMID- 23165061
TI  - High-speed fluorescence imaging and intensity profiling of femtosecond-induced
      calcium transients.
AB  - We have demonstrated a combined imaging system, where the physiology of
      biological specimens can be imaged and profiled at 10-20 frames per second whilst
      undergoing femtosecond laser irradiation. Individual GH3 cells labeled with the
      calcium fluorophore Fluo-3 were stimulated using a counter-propagating focused
      femtosecond beam with respect to the imaging system. As a result of the
      stimulation, calcium waves can be generated in COS cells, and laser-induced
      calcium oscillations are initiated in the GH3 cells. Single-photon fluorescence
      images and intensity profiles of the targeted specimens are sampled in real-time
      using a modified PerkinElmer UltraView LCI microscope.

PMID- 23165062
TI  - Virtual contrast for coronary vessels based on level set generated subvoxel
      accurate centerlines.
AB  - We present a tool for tracking coronary vessels in MRI scans of the human heart
      to aid in the screening of heart diseases. The vessels are identified through a
      single click inside each vessel present in a standard orthogonal view. The vessel
      identification results from a series of computational steps including eigenvalue
      analysis of the Hessian of the MRI image followed by a level set-based extraction
      of the vessel centerline. All identified vessels are highlighted using a virtual
      contrast agent and displayed simultaneously in a spherical curved reformation
      view. In cases of over segmentation, the vessel traces can be shortened by a
      click on each vessel end point. Intermediate analysis results of the vessel
      computation steps can be displayed as well. We successfully validated the tool on
      40 MRI scans demonstrating accuracy and significant time savings over manual
      vessel tracing.

PMID- 23165063
TI  - Impacts of Filtration on Contrast-Detail Detectability of an X-ray Imaging
      System.
AB  - The purpose of this study is to investigate the impacts of added filtration on
      the contrast-detail detectability of a digital X-ray imaging system for small
      animal studies. A digital X-ray imaging system specifically designed for small
      animal studies was used. This system is equipped with a micro X-ray source with a
      tungsten target and a beryllium window filtration and a CCD-based digital
      detector. Molybdenum filters of 0 mm, 0.02 mm, and 0.05 mm in thickness were
      added. The corresponding X-ray spectra and contrast-detail detectabilities were
      measured using two phantoms of different thicknesses simulating breast tissue
      under different exposures. The added Mo filters reduced the low-energy as well as
      the high-energy photons, hence providing a narrowband for imaging quality
      improvement. In the experiments with a 1.15 cm phantom, the optimal image
      detectability was observed using 22 kVp and the 0.05 mm Mo filter. With the 2.15
      cm phantom, the best detectability was obtained with 22 kVp and the 0.02 mm Mo
      filter. Our experiments showed that appropriate filtrations could reduce certain
      low- and high-energy components of X-ray spectra which have limited contributions
      to image contrast. At the same time, such filtration could improve the contrast
      detail detectability, particularly at relatively low kVp and high filtration.
      Therefore, optimal image quality can be obtained with the same absorbed radiation
      dose by the subjects when appropriate filtration is used.

PMID- 23165064
TI  - A wavelet packets approach to electrocardiograph baseline drift cancellation.
AB  - Baseline wander elimination is considered a classical problem. In
      electrocardiography (ECG) signals, baseline drift can influence the accurate
      diagnosis of heart disease such as ischemia and arrhythmia. We present a wavelet
      transform- (WT-) based search algorithm using the energy of the signal in
      different scales to isolate baseline wander from the ECG signal. The algorithm
      computes wavelet packet coefficients and then in each scale the energy of the
      signal is calculated. Comparison is made and the branch of the wavelet binary
      tree corresponding to higher energy wavelet spaces is chosen. This algorithm is
      tested using the data record from MIT/BIH database and excellent results are
      obtained.

PMID- 23165066
TI  - Prevention. Multivitamins do not reduce the risk of cardiovascular disease.

PMID- 23165065
TI  - Potential biological chemistry of hydrogen sulfide (H2S) with the nitrogen
      oxides.
AB  - Hydrogen sulfide, an important gaseous signaling agent generated in numerous
      biological tissues, influences many physiological processes. This biological
      profile seems reminiscent of nitric oxide, another important endogenously
      synthesized gaseous signaling molecule. Hydrogen sulfide reacts with nitric oxide
      or oxidized forms of nitric oxide and nitric oxide donors in vitro to form
      species that display distinct biology compared to both hydrogen sulfide and NO.
      The products of these interesting reactions may include small-molecule S
      nitrosothiols or nitroxyl, the one-electron-reduced form of nitric oxide. In
      addition, thionitrous acid or thionitrite, compounds structurally analogous to
      nitrous acid and nitrite, may constitute a portion of the reaction products. Both
      the chemistry and the biology of thionitrous acid and thionitrite, compared to
      nitric oxide or hydrogen sulfide, remain poorly defined. General mechanisms for
      the formation of S-nitrosothiols, nitroxyl, and thionitrous acid based upon the
      ability of hydrogen sulfide to act as a nucleophile and a reducing agent with
      reactive nitric oxide-based intermediates are proposed. Hydrogen sulfide
      reactivity seems extensive and could have an impact on numerous areas of redox
      controlled biology and chemistry, warranting more work in this exciting and
      developing area.

PMID- 23165067
TI  - Stem cells. Could it be TIME to abandon BMCs?

PMID- 23165068
TI  - Biomarkers. Screening for C-reactive protein in CVD prediction.
AB  - Adding C-reactive protein (CRP) level to conventional cardiovascular risk models
      has been suggested to improve risk prediction for cardiovascular events. However,
      evaluation of the potential impact of CRP measurement in cardiovascular risk
      management will require studies designed to quantify the effect of additional CRP
      assessment on medical decision-making, patient outcomes, and cost-effectiveness.

PMID- 23165069
TI  - Diabetes. Dual RAAS blocker trial stopped prematurely.

PMID- 23165070
TI  - Antiplatelet therapy. ARCTIC leaves platelet testing out in the cold.

PMID- 23165071
TI  - Venous thromboembolism. Aspirin ASPIREs to reduce vascular events after VTE.

PMID- 23165073
TI  - Lipids. Antibodies against PCSK9--a new era of therapy.

PMID- 23165072
TI  - Timely and optimal treatment of patients with STEMI.
AB  - Fibrinolysis is recommended in European and US guidelines for patients with ST
      segment elevation myocardial infarction (STEMI) when a strategy of primary
      percutaneous coronary intervention (PPCI) is associated with >=120 min delay from
      first medical contact (FMC), defined as call to the emergency medical services or
      self-presentation at hospital. Current evidence indicates that reperfusion
      therapy should be initiated as soon as possible after FMC. However, fibrinolysis
      cannot be initiated instantaneously at FMC, and PPCI is superior to fibrinolysis
      in reducing mortality if the extra time needed to perform PPCI instead of
      fibrinolysis (so-called PCI-related delay) is <120 min. During the past 10 years,
      the terms 'FMC-to-PPCI delay' and 'PCI-related delay' have been used in
      guidelines synonymously; however, a distinction should be made between the
      recommended FMC-to-PPCI delay and the acceptable PCI-related delay. In the
      future, an ideal recommendation would be to initiate reperfusion as soon as
      possible, preferably within 120 min of FMC in the case of PPCI. When the expected
      PCI-related delay is <120 min, PPCI should be the preferred reperfusion strategy,
      even if the FMC-to-PPCI delay is >120 min. Setting up a health-care system
      enabling prehospital diagnosis of STEMI with field triage of patients directly to
      catheterization laboratories at large-volume PCI centres (bypassing local
      hospitals, coronary care units, emergency departments, and intensive care units)
      will help to increase the proportion of patients with STEMI who will benefit from
      PPCI.

PMID- 23165074
TI  - Lipids. Dalcetrapib raises HDL-cholesterol level, but does not reduce cardiac
      risk.

PMID- 23165075
TI  - Heart failure. Optimal postdischarge management of chronic HF.
AB  - Not all strategies for the management of chronic heart failure have been shown to
      be equally effective in improving outcomes, and the ideal programme has yet to be
      defined. The WHICH? trial sheds some light on whether a clinical, in-hospital or
      a home-based strategy of care is superior and cost-effective.

PMID- 23165076
TI  - Heart failure. Drugs outperform ultrafiltration in acute cardiorenal syndrome.

PMID- 23165078
TI  - Heart failure. Promising data for serelaxin.

PMID- 23165080
TI  - Physiological interference in effective connectivity of action network.
AB  - The effect of temporal interference of physiological signals on time-lag
      effective connectivity, derived from a functional network connectivity tool box
      (FNC), was examined by a blood-oxygen-level-dependent functional MRI study of
      action. The known effect of physiological signals on time-lag FNC was verified by
      (a) comparison of time-lag FNC analyses without and with retrospective image
      based correction (RETROICOR) and (b) the other time-lag FNC analysis including
      the ventricular component related to the cerebrospinal fluid with dominant
      physiological effects. Twenty-five right-handed normal individuals performed
      motor task with motor response by the right middle/index fingers. Behavioral data
      of the reaction time (RT) and physiological signals (electrocardiogram,
      respiration, and pulsation) were recorded during neuroimaging studies of a 2-s
      repetition time at 3T. After standard image preprocessing, RETROICOR of the
      physiological effects and group independent component analysis (ICA), five action
      related components were selected from 59 ICA components according to spatial
      extension involving known functional correlates of visuomotor tasks. Time-lag FNC
      was constructed by calculating the maximal correlation coefficients among five
      selected components. Attenuation of the physiological effect at 0.02-0.25 Hz was
      an average of 0.63 dB after RETROICOR (P<0.0005). Results of FNC analyses without
      and with RETROICOR were compatible with the action networks using the right hand.
      On the basis of the time-lag FNC after RETROICOR, the connectivity among the
      ventricular component and other components of action network attenuated. The FNC
      map with RETROICOR was more explicable with known action networks, for example
      interhemispheric inhibition. The effects of physiological signals significantly
      misled the interpretation of time-lag FNC in terms of direction and connectivity
      strength.

PMID- 23165081
TI  - [Was the current surplus of neurosurgeons predictable in 2009? Analysis of the
      situation based on the Report of supply and demand of medical specialists in
      Spain (2008-2025)].
AB  - INTRODUCTION: In 2009 the Spanish Ministry of Health (SMH) published the report
      of supply and demand of medical specialists in Spain (2008-2025), in which our
      specialty was considered as presenting a moderate deficit of consultants.
      However, Spanish neurosurgery is currently in a situation of having a surplus of
      neurosurgeons. OBJECTIVES: To determine whether it was possible to predict the
      current excess of neurosurgeons in 2009 and to forecast the most likely
      perspective of supply and demand in 2017. MATERIAL AND METHODS: Raw data
      extracted from the SMH report, information on the ages of the Spanish
      neurosurgeons obtained from the study performed by our Board of Directors in
      2001, and annual mortality rates for different age ranges provided by the
      National Institute of Statistics, were used to predict the evolution of supply
      and demand of neurosurgeons for the periods 2008-2012 and 2013-2017. RESULTS: The
      current situation of an excess of specialists was predictable in 2009, and if
      appropriate measures are not taken, a surplus of more than 100 neurosurgeons is
      likely in 2017, with an unemployment rate above 26% in the worst scenario.
      CONCLUSIONS: In order to match the actual and future demand of specialists, it is
      necessary and urgent to reduce the number of neurosurgical in-training positions.
      To achieve this goal, it is essential to obtain periodical and up-to-date
      structural information of the different Neurosurgery Departments and Units, and
      to revisit the accreditation terms of the more than fifty current teaching units.

PMID- 23165085
TI  - The role of dietary protein in blood pressure regulation.
AB  - PURPOSE OF REVIEW: Despite a considerable amount of research, the blood pressure
      (BP) lowering effect of dietary proteins is still not fully established. This
      review discusses the most recent findings on BP lowering of dietary proteins and
      protein sources, the possible mechanisms and the safety of increasing protein
      intake. RECENT FINDINGS: Recent short-term, strictly controlled, randomized
      clinical trials show a BP lowering effect of increased protein intake. Longer
      term trials, however, show inconsistent results. Because all recent trials
      exchanged carbohydrates, and not fats, for proteins, the question remains whether
      potential beneficial effects of high protein diets are due to increased protein
      intake or decreased carbohydrate intake. No clear differences between plant
      protein and animal protein are found in observational studies, and trials
      comparing plant versus animal protein are lacking. Different protein sources may
      lower BP via different mechanisms, which might explain divergent findings.
      Potential harms of high protein diets are not confirmed in recent trials in
      healthy persons. SUMMARY: Increasing dietary protein intake or decreasing
      carbohydrate intake within reasonable limits may be beneficial for BP. The most
      and least beneficial protein sources still need to be determined.

PMID- 23165086
TI  - Plant sterols and atherosclerosis.
AB  - PURPOSE OF REVIEW: Plant sterols as ingredients to functional foods are
      recommended for lowering LDL cholesterol. However, there is an ongoing discussion
      whether the use of plant sterols is safe. RECENT FINDINGS: Genetic analyses
      showed that common variants of the ATP binding cassette transporter G8 (ABCG8)
      and ABO genes are associated with elevated circulating plant sterols and higher
      risk for cardiovascular disease. However, these data do not prove a causal role
      for plant sterols in atherosclerosis because the risk alleles in ABCG8 and ABO
      are also related to elevated total and LDL cholesterol levels. The ABO locus
      exhibits still further pleiotropy. Moreover, analyses in the general population
      indicated that moderately elevated circulating plant sterols are not correlated
      with present or future vascular disease. In agreement, novel studies using food
      frequency questionnaires, studies in experimental animals, and dietary
      intervention studies support that ingestion of plant sterols may be beneficial to
      cardiovascular health. SUMMARY: Taken together, current evidence supports the
      recommendations for the use of plant sterols as LDL cholesterol-lowering agents.
      Nevertheless, a prospective, randomized, controlled, double-blinded, intervention
      trial conclusively showing that plant sterol supplementation will prevent hard
      cardiovascular endpoints is not available to date.

PMID- 23165087
TI  - Brain imaging in the context of food perception and eating.
AB  - PURPOSE OF REVIEW: Eating behavior depends heavily on brain function. In recent
      years, brain imaging has proved to be a powerful tool to elucidate brain function
      and brain structure in the context of eating. In this review, we summarize recent
      findings in the fast growing body of literature in the field and provide an
      overview of technical aspects as well as the basic brain mechanisms identified
      with imaging. Furthermore, we highlight findings linking neural processing of
      eating-related stimuli with obesity. RECENT FINDINGS: The consumption of food is
      based on a complex interplay between homeostatic and hedonic mechanisms. Several
      hormones influence brain activity to regulate food intake and interact with the
      brain's reward circuitry, which is partly mediated by dopamine signaling.
      Additionally, it was shown that food stimuli trigger cognitive control mechanisms
      that incorporate internal goals into food choice. The brain mechanisms observed
      in this context are strongly influenced by genetic factors, sex and personality
      traits. SUMMARY: Overall, a complex picture arises from brain-imaging findings,
      because a multitude of factors influence human food choice. Although several key
      mechanisms have been identified, there is no comprehensive model that is able to
      explain the behavioral observations to date. Especially a careful
      characterization of patients according to genotypes and phenotypes could help to
      better understand the current and future findings in neuroimaging studies.

PMID- 23165088
TI  - Correlation between genotypic (V3 population sequencing) and phenotypic (Trofile
      ES) methods of characterizing co-receptor usage of HIV-1 from 200 treatment-naive
      HIV patients screened for Study A4001078.
AB  - Assessment of HIV-1 co-receptor usage is essential to identify patients who are
      likely to respond to maraviroc (MVC)-containing regimens. Co-receptor usage of
      plasma virus from all treatment-naive patients screened for a MVC clinical trial
      was assessed using phenotypic and genotypic methodologies to evaluate concordance
      between testing methods and to assess the quantity of CXCR4-using (non-R5) virus
      in samples giving discordant results. Co-receptor usage was prospectively
      measured using the enhanced sensitivity Trofile assay (Trofile ES) to screen
      patients for enrollment in Study A4001078. Population and deep sequencing
      methodologies were utilized retrospectively to analyze all screening samples,
      with co-receptor usage determined using the geno2pheno algorithm. Concordance
      between methods was explored using descriptive statistics. The quantity of non-R5
      virus in all samples was measured using deep sequencing. Trofile ES and matched
      genotype results were obtained for 199screening samples. Concordance of Trofile
      ES with population genotyping (5.75% false-positive rate [FPR]) and deep
      sequencing (3.5% FPR; 2% non-R5 threshold) was 91.7% and 89.6%, respectively.
      Population genotype data were available for all samples with non-reportable
      Trofile ES results; the distribution of co-receptor usage in this set was
      consistent with that in the overall population: 75% (12/16) R5 and 25% (4/16) non
      R5. The majority of samples contained non-R5 plasma HIV-1 RNA estimated at either
      <1 log(10) (62.0%) or ?4 log(10) (30.5%) copies/mL; the absolute amount of
      detectable non-R5 virus remained stable between screening and baseline visits.
      Samples originally classified as non-R5 by Trofile ES but R5 by population
      sequencing had a relatively low absolute amount of non-R5 virus (mean 2.1%,
      median 0.1%). The determination of co-receptor usage using either Trofile ES or
      genotyping methodologies showed similar frequencies of R5 and non-R5 virus in
      this treatment-naive study population. For both concordant and discordant
      samples, population sequencing appropriately identified R5 samples with low
      levels of non-R5-using virus.

PMID- 23165089
TI  - Catheterized guinea pigs infected with Ebola Zaire virus allows safer sequential
      sampling to determine the pharmacokinetic profile of a phosphatidylserine
      targeting monoclonal antibody.
AB  - Sequential sampling from animals challenged with highly pathogenic organisms,
      such as haemorrhagic fever viruses, is required for many pharmaceutical studies.
      Using the guinea pig model of Ebola virus infection, a catheterized system was
      used which had the benefits of allowing repeated sampling of the same cohort of
      animals, and also a reduction in the use of sharps at high biological
      containment. Levels of a PS-targeting antibody (Bavituximab) were measured in
      Ebola-infected animals and uninfected controls. Data showed that the
      pharmacokinetics were similar in both groups, therefore Ebola virus infection did
      not have an observable effect on the half-life of the antibody.

PMID- 23165090
TI  - Design, implementation, and application of a microresonator platform for
      measuring energy dissipation by internal friction in nanowires.
AB  - Accurate measurements of internal friction in nanowires are required for the
      rational design of high-Q resonators used in nanoelectromechanical systems and
      for fundamental studies of nanomechanical behavior. However, measuring internal
      friction is challenging because of the difficulties associated with identifying
      the contributions of material dissipation to structural damping. Here, we present
      an approach for overcoming these difficulties by using a composite microresonator
      platform that is calibrated against the ultimate limits of thermoelastic damping.
      The platform consists of an array of nanowires patterned at the root of a low
      loss single-crystal silicon microcantilever. The structure is processed using a
      lift-off technique, implemented using electron-beam lithography, to achieve
      excellent control over the size, alignment, dispersion and location of the
      nanowire array. As the first application of this platform, we measured internal
      friction at room temperature in aluminum nanowires that ranged from 50 to 100 nm
      in thickness and 100 to 400 nm in width. Internal friction is ~0.03 at
      frequencies of 6.5-21 kHz. Transmission electron microscopy of the
      nanocrystalline grain structure, and comparison with previously measured values
      of internal friction in continuous thin films of aluminum, suggest that grain
      boundary sliding is a major source of internal friction in these nanowires.

PMID- 23165091
TI  - The effects of stoichiometry on the mechanical properties of icosahedral boron
      carbide under loading.
AB  - The  effects of stoichiometry on the atomic structure and the related mechanical
      properties of boron carbide (B(4)C) have been studied using density functional
      theory and quantum molecular dynamics simulations. Computational cells of boron
      carbide containing up to 960 atoms and spanning compositions ranging from 6.7% to
      26.7% carbon were used to determine the effects of stoichiometry on the atomic
      structure, elastic properties, and stress-strain response as a function of
      hydrostatic, uniaxial, and shear loading paths. It was found that different
      stoichiometries, as well as variable atomic arrangements within a fixed
      stoichiometry, can have a significant impact on the yield stress of boron carbide
      when compressed uniaxially (by as much as 70% in some cases); the significantly
      reduced strength of boron carbide under shear loading is also demonstrated.

PMID- 23165093
TI  - RNA/DNA co-analysis from human saliva and semen stains--results of a third
      collaborative EDNAP exercise.
AB  - A third collaborative exercise on RNA/DNA co-analysis for body fluid
      identification and STR profiling was organized by the European DNA Profiling
      Group (EDNAP). Twenty saliva and semen stains, four dilution series (10-0.01 MUl
      saliva, 5-0.01 MUl semen) and, optionally, bona fide or mock casework samples of
      human or non-human origin were analyzed by 20 participating laboratories using an
      RNA extraction or RNA/DNA co-extraction method. Two novel mRNA multiplexes were
      used: a saliva triplex (HTN3, STATH and MUC7) and a semen pentaplex (PRM1, PRM2,
      PSA, SEMG1 and TGM4). The laboratories used different chemistries and
      instrumentation and a majority (16/20) were able to successfully isolate and
      detect mRNA in dried stains. The simultaneous extraction of RNA and DNA from
      individual stains not only permitted a confirmation of the presence of
      saliva/semen (i.e. tissue/fluid source of origin), but allowed an STR profile of
      the stain donor to be obtained as well. The method proved to be reproducible and
      sensitive, with as little as 0.05 MUl saliva or semen, using different analysis
      strategies. Additionally, we demonstrated the ability to positively identify the
      presence of saliva and semen, as well as obtain high quality DNA profiles, from
      old and compromised casework samples. The results of this collaborative exercise
      involving an RNA/DNA co-extraction strategy support the potential use of an mRNA
      based system for the identification of saliva and semen in forensic casework that
      is compatible with current DNA analysis methodologies.

PMID- 23165094
TI  - IT Future of Medicine: from molecular analysis to clinical diagnosis and improved
      treatment.
AB  - The IT Future of Medicine (ITFoM, http://www.itfom.eu/) initiative will produce
      computational models of individuals to enable the prediction of their future
      health risks, progression of diseases and selection and efficacy of treatments
      while minimising side effects. To be able to move our health care system to treat
      patients as individuals rather than as members of larger, divergent groups, the
      ITFoM initiative, proposes to integrate molecular, physiological and anatomical
      data of every person in 'virtual patient' models. The establishment of such
      'virtual patient' models is now possible due to the enormous progress in
      analytical techniques, particularly in the '-omics' technology areas and in
      imaging, as well as in sensor technologies, but also due to the immense
      developments in the ICT field. As one of six Future and Emerging Technologies
      (FET) Flagship Pilot Projects funded by the European Commission, ITFoM with more
      than 150 academic and industrial partners from 34 countries, will foster the
      development in functional genomics and computer technologies to generate 'virtual
      patient' models to make them available for clinical application. The increase in
      the capacity of next generation sequencing systems will enable the high
      throughput analysis of a large number of individuals generating huge amounts of
      genome, epigenome and transcriptome data, but making it feasible to apply deep
      sequencing in the clinic to characterise not only the patient's genome, but also
      individual samples, for example, from tumours. The genome profile will be
      integrated with proteome and metabolome information generated via new powerful
      chromatography, mass spectrometry and nuclear magnetic resonance techniques. The
      individualised model will not only enable the analysis of the current situation,
      but will allow the prediction of the response of the patient to different therapy
      options or intolerance for certain drugs.

PMID- 23165095
TI  - From genetic discovery to future personalized health research.
AB  - During the past ten years the field of human disease genetics has made major
      leaps, including the completion of the Human Genome Project, the HapMap Project,
      the development of the genome-wide association (GWA) studies to identify common
      disease-predisposing variants and the introduction of large-scale whole-genome
      and whole-exome sequencing studies. The introduction of new technologies has
      enabled researchers to utilize novel study designs to tackle previously
      unexplored research questions in human genomics. These new types of studies
      typically need large sample sizes to overcome the multiple testing challenges
      caused by the huge number of interrogated genetic variants. As a consequence,
      large consortia-studies are at present the default in disease genetics research.
      The systematic planning of the GWA-studies was a key element in the success of
      the approach. Similar planning and rigor in statistical inferences will probably
      be beneficial also to future sequencing studies. Already today, the next
      generation exome sequencing has led to the identification of several genes
      underlying Mendelian diseases. In spite of the clear benefits, the method has
      proven to be more challenging than anticipated. In the case of complex diseases,
      next-generation sequencing aims to identify disease-associated low-frequency
      alleles. However, their robust detection will require very large study samples,
      even larger than in the case of the GWA-studies. This has stimulated study
      designs that capitalize on enriching sets of low-frequency alleles, for example,
      studies focusing on population isolates such as Finland or Iceland. One example
      is the collaborative SISu Project (Sequencing Initiative Suomi) that aims to
      provide near complete genome variation information from Finnish study samples and
      pave the way for large, nationwide genome health initiative studies.

PMID- 23165096
TI  - DNA sequencing - spanning the generations.
AB  - Nucleic acid sequencing is the mainstay of biological research. There are several
      generations of DNA sequencing technologies that can be well characterized through
      their nature and the kind of output they provide. Dideoxy terminator sequencing
      developed by Sanger dominated for 30 years and was the workhorse used for the
      Human Genome Project. In 2005 the first 2nd generation sequencer was presented
      with an output orders of magnitude higher than Sanger sequencing and dramatically
      decreased cost. We are now at the dawn of 3rd generation with nanopore systems
      that are being developed for DNA sequencing. Meanwhile the field is also
      broadening into applications that complement 1st, 2nd and 3rd generation
      sequencing systems to get high resolution genetic information. The REvolutionary
      Approaches and Devices for Nucleic Acid analysis (READNA) consortium funded by
      the European Commission under FP7 has made great contributions to the development
      of new nucleic acid analysis methodology.

PMID- 23165097
TI  - Experimental and computational methods for the analysis and modeling of signaling
      networks.
AB  - External cues are processed and integrated by signal transduction networks that
      drive appropriate cellular responses. Characterizing these programs, as well as
      how their deregulation leads to disease, is crucial for our understanding of cell
      biology. The past ten years have witnessed a gradual increase in the number of
      molecular parameters that can be simultaneously measured in a sample. Moreover
      our capacity to handle multiple samples in parallel has expanded, thus allowing a
      deeper profiling of cellular states under diverse experimental conditions. These
      technological advances have been complemented by the development of computational
      methods aimed at mining, analyzing and modeling these data. In this review we
      give a general overview of the most important experimental and computational
      techniques used in the field and describe several interesting application of
      these methodologies. We conclude by highlighting the issues that we think will
      keep researchers in the field busy in the next few years.

PMID- 23165098
TI  - The progress of proteomic approaches in searching for cancer biomarkers.
AB  - Biomarkers are indicators of a specific biological state. Their detection in
      pathological conditions, such as cancer, is important for clinical disease
      management. One of their greatest values could be in early diagnosis and
      detection of neoplasms when the cancer is more manageable. Protein biomarkers are
      expected to be reliable predictors of pathological conditions, as they represent
      the endpoint of biological processes. The proteomic methodology has rapidly
      evolved in the past ten years, thus enabling discovery of a vast amount of
      potential biomarker candidates. However, the majority of novel candidates have
      not yet reached the integration into clinical environment. To do that, well
      constructed large population validation studies are necessary as well as
      development of new algorithms for deciphering complex biological interactions and
      their involvement in pathological processes. This review focuses on advances in
      classical proteomic approaches and emerging high-throughput proteomic
      technologies for identifying cancer biomarkers.

PMID- 23165099
TI  - The emergence of Semantic Systems Biology.
AB  - Over the past decade the biological sciences have been widely embracing Systems
      Biology and its various data integration approaches to discover new knowledge.
      Molecular Systems Biology aims to develop hypotheses based on integrated, or
      modelled data. These hypotheses can be subsequently used to design new
      experiments for testing, leading to an improved understanding of the biology; a
      more accurate model of the biological system and therefore an improved ability to
      develop hypotheses. During the same period the biosciences have also eagerly
      taken up the emerging Semantic Web as evidenced by the dedicated exploitation of
      Semantic Web technologies for data integration and sharing in the Life Sciences.
      We describe how these two approaches merged in Semantic Systems Biology: a data
      integration and analysis approach complementary to model-based Systems Biology.
      Semantic Systems Biology augments the integration and sharing of knowledge, and
      opens new avenues for computational support in quality checking and automated
      reasoning, and to develop new, testable hypotheses.

PMID- 23165100
TI  - Regulation of Pichia pastoris promoters and its consequences for protein
      production.
AB  - The methylotrophic yeast Pichia pastoris is a widely used host for heterologous
      protein production. Along with favorable properties such as growth to high cell
      density and high capacities for protein secretion, P. pastoris provides a strong,
      methanol inducible promoter of the alcohol oxidase 1 (AOX1) gene. The regulation
      of this promoter has been extensively studied in recent years by characterizing
      cis-acting sequence elements and trans-acting factors, revealing insights into
      underlying molecular mechanisms. However, new alternative promoters have also
      been identified and characterized by means of their transcriptional regulation
      and feasibility for protein production using P. pastoris. Besides the often
      applied GAP promoter, these include a variety of constitutive promoters from
      housekeeping genes (e.g. TEF1, PGK1, TPI1) and inducible promoters from
      particular biochemical pathways (e.g. PHO89, THI11, AOD). In addition to these
      promoter sequence/function based studies, transcriptional regulation has also
      been investigated by characterizing transcription factors (TFs) and their modes
      of controlling bioprocess relevant traits. TFs involved in such diverse cellular
      processes such as the unfolded protein response (UPR) (Hac1p), iron uptake
      (Fep1p) and oxidative stress response (Yap1p) have been studied. Understanding of
      these natural transcriptional regulatory networks is a helpful basis for
      synthetic biology and metabolic engineering approaches that enable the design of
      tailor-made production strains.

PMID- 23165101
TI  - Challenges and perspectives to improve crop drought and salinity tolerance.
AB  - Drought and high salinity are two major abiotic stresses affecting crop
      productivity. Therefore, the development of crops better adapted to cope with
      these stresses represents a key goal to ensure global food security to an
      increasing world population. Although many genes involved in the response to
      these abiotic stresses have been extensively characterised and some stress
      tolerant plants developed, the success rate in producing stress-tolerant crops
      for field conditions has been thus far limited. In this review we discuss
      different factors hampering the successful transfer of beneficial genes from
      model species to crops, emphasizing some limitations in the phenotypic
      characterisation and definition of the stress tolerant plants developed so far.
      We also highlight some technological advances and different approaches that may
      help in developing cultivated stress tolerant plants.

PMID- 23165102
TI  - A novel image processing method to determine the nutritional condition of
      lobsters.
AB  - The digestive gland of crustacean is involved in various metabolic activities,
      including the synthesis and secretion of digestive enzymes that begin the process
      of food digestion, intracellular digestion and absorption of nutrients, storage
      of reserves, and disposal of waste products. It consists of two glandular lobes
      which extensively subdivide to form a complex of blind-ending tubules, whose
      size, surface area, and digestive cells are associated with intracellular
      digestion and the nutritional status of the organism. The aim of this paper was
      to study the morphology of the digestive gland in various lobster species and
      calculate the surface area of tubules, lumen and digestive cells (R-, F-, and B
      cells) and their ratios to total tubule surface area. The similarity in ratios
      obtained in this study between individual lobsters suggests that the method
      developed in this study can be successfully applied to a range of species. This
      study describes a novel image processing algorithm for the automatic measurement
      of the hepatopancreas structure using stained cross sections of digestive gland
      tubules. The proposed new methodology could be used for studying the physiology
      and nutrient metabolism of lobsters and other crustaceans. The computer-aided
      analysis described in this paper is accurate for the quantitative assessment of
      the lobster's digestive gland structure.

PMID- 23165103
TI  - Stapled anopexy as a day surgery procedure: our experience over 400 cases.
AB  - BACKGROUND: In 1988, Longo proposed a new treatment for haemorrhoidal disease. In
      western countries day surgery procedures are becoming more and more common. We
      propose a new protocol for outpatient haemorrhoidopexy. PATIENTS AND METHODS:
      From 2003 to 2010, we performed 403 out-patient stapled haemorrhoidopexies under
      spinal anaesthesia, on patients with symptomatic grade III and IV haemorrhoid
      disease. We used PPH 01 and PPH 03 staplers (Ethicon Endosurgery, Cincinnati, OH,
      USA). We assessed early and late postoperative pain with a Visual Analogue Scale
      (VAS), and clinical postoperative examinations were performed 7 days, 6 months,
      and 1, 3 and 5 years after surgery. RESULTS: The mean surgery time was about 20
      min (range 13-39 min). Out of 403 patients, 41 were not dischargeable as a result
      of urine retention, severe pain or mild bleeding. Twenty-two patients reported
      transient faecal urgency, while no patient complained of anal incontinence.
      CONCLUSIONS: Our experience with 403 patients demonstrated that stapled
      haemorrhoidopexy is feasible and safe as a day surgery procedure. However,
      careful preoperative planning is necessary in order to evaluate the patients'
      health status and the consequent perioperative and postoperative risk. Our
      results are positive in terms of surgical safety and postoperative recovery time.

PMID- 23165104
TI  - N(2)O emission in a partial nitrification system: dynamic emission
      characteristics and the ammonium-oxidizing bacteria community.
AB  - This study attempts to elucidate the dynamics of nitrous oxide (N(2)O) emission
      and investigate the evolution of the ammonium-oxidizing bacteria (AOB) community
      in a partial nitrification system producing an influent suitable for the anammox
      process. Based on long-term monitoring, (0.80 +/- 0.19, n = 7)% of the incoming
      nitrogen load was emitted as N(2)O. During the partial nitrification process, the
      N(2)O emission rate reached a maximum at the beginning of the aerobic period and
      stabilized at a low level after an initial peak. Moreover, the quantity of N(2)O
      emission increased quickly at the beginning of the cycle operation and then
      production slowed after 30 min. According to polymerase chain reaction (PCR) and
      denaturing gradient gel electrophoresis (DGGE) analysis, the dominant AOB causing
      the N(2)O emission from the partial nitrification system were Nitrosomonas sp.
      Both Nitrosomonas sp. Nm33 and Nitrosomonas sp. Nm58 were enriched at high
      ammonia concentrations.

PMID- 23165105
TI  - Le Fort I osteotomies using Bio-Oss(r) collagen to promote bony union: a
      prospective clinical split-mouth study.
AB  - The purpose of this study was to evaluate whether a bone substitute can be used
      to promote bony union in patients undergoing maxillary advancement after Le Fort
      l osteotomy. Nine patients were treated bilaterally with Le Fort I osteotomies
      and maxillary advancements of 5mm or less. In each patient, one gap was grafted
      with the bone substitute Bio-Oss((r)) Collagen (BOC). The contralateral site was
      left empty and served as control. After 6 months there were still empty gaps in
      the control sites of three patients, while in the grafted sites all gaps were
      completely filled with bone. The histomorphometric analysis performed with
      biopsies from the region of the original gap showed a similar amount of new bone
      in both groups, however, in the test group the mean overall amount of the
      mineralized fraction was higher compared to the control group (test site 65.0+/
      6.2%, control site 38.9+/-32.6%). The bone substitute seemed to be a suitable
      material to promote bony union in Le Fort I osteotomies. Further studies are
      needed to analyse whether this technique is efficient in preventing relapse and
      promoting bony union in larger advancements.

PMID- 23165106
TI  - The use of suture-less technique following third molar surgery.

PMID- 23165107
TI  - Predisposition for self-destruction? Affective temperaments as a suicide risk
      factor in patients with mood disorders.

PMID- 23165109
TI  - Impaired pressure natriuresis is associated with interstitial inflammation in
      salt-sensitive hypertension.
AB  - PURPOSE OF REVIEW: Impairment of the pressure natriuresis relationship is a
      central event in the pathogenesis of hypertension. Renal tubulointerstitial
      inflammation results in salt-sensitive hypertension and, until recently, the
      changes in pressure natriuresis induced by renal inflammation received little
      attention. RECENT FINDINGS: Oxidative stress and increased intrarenal angiotensin
      II activity, in association with rarefaction and loss of peritubular vascular
      network, may be involved in the inflammation-induced blunting of the natriuresis
      resulting from increments in renal perfusion pressure. SUMMARY: Here, we review
      the mechanisms for the impairment in pressure natriuresis resulting from renal
      tubulointerstitial inflammation in reference to the normal physiologic mechanisms
      involved in this response.

PMID- 23165110
TI  - Visit-to-visit blood pressure variability and risk for progression of
      cardiovascular and renal diseases.
AB  - PURPOSE OF REVIEW: Recent data have highlighted the shortcomings of the usual
      blood pressure hypothesis in posthoc analyses of randomized controlled trials led
      in populations at high cardiovascular risk and have emphasized the importance of
      an increased visit-to-visit variability of blood pressure in predicting
      cardiovascular events. RECENT FINDINGS: Over the last 2 years, the prognostic
      value of visit-to-visit blood pressure variability has been substantially
      confirmed in a wide spectrum of clinical populations, in studies investigating
      both cardiovascular outcomes and target organ damage. SUMMARY: There is an
      obvious need to design studies to prospectively determine the causes of increased
      visit-to-visit blood pressure variability, its best estimate and whether or not
      treatments that reduce blood pressure variability (and to what extent/target)
      improve clinical outcome.

PMID- 23165111
TI  - The evolving role of renal pericytes.
AB  - PURPOSE OF REVIEW: The purpose of this review is to focus on the most recent
      developments in our understanding of the physiological and pathophysiological
      role(s) that renal pericytes play in the kidney. We will highlight the most
      important and interesting advances made in the last 12 months and aim to provide
      a concise summary of the exciting progress in this field. RECENT FINDINGS:
      Pericytes have increasingly been the subject of much interest in the renal field,
      with particular attention focusing on their key role as regulators of medullary
      blood flow (MBF), their ability to coordinate tubular and vascular function via
      tubulovascular cross-talk mechanisms, and most recently, their role in the
      pathogenesis of renal diseases such as fibrosis and associated forms of chronic
      disease. SUMMARY: Pericyte-mediated regulation of vasa recta diameter provides
      compelling evidence to support regulated MBF, a notoriously controversial
      subject. Coordination of tubular and vascular function by pericytes, particularly
      in salt-sensitive animal models, provides important mechanistic information
      regarding the physiological workings of the medulla in health and renal disease.
      Moreover, the emergent role of renal pericytes in vessel rarefication during
      fibrosis promises to reveal novel therapeutic targets to counteract
      devascularization, disease progression and loss of kidney function.

PMID- 23165112
TI  - IHG-1 amplifies TGF-beta1 signalling and mitochondrial biogenesis and is
      increased in diabetic kidney disease.
AB  - PURPOSE OF REVIEW: This review focuses on the role of the mitochondrial protein
      induced in high glucose 1 (IHG-1) in kidney fibrosis. RECENT FINDINGS: Diabetic
      nephropathy is the most common cause of end-stage renal disease. Transforming
      growth factor-beta1 (TGF-beta1) is a pivotal mediator of fibrosis and diabetic
      nephropathy. IHG-1 was identified in a screen for genes differentially expressed
      in renal cells exposed to high glucose. Here we review the biology of this novel
      functionally uncharacterized gene transcript. Data from human biopsy material and
      experimental models indicate increased expression of IHG-1 is a critical
      component of fibrogenesis as it amplifies TGF-beta1 signalling. IHG-1 is
      expressed in mitochondria, stabilizes PGC-1alpha protein and increases
      mitochondrial biogenesis. Recently the crystal structure of IHG-1 has been
      determined revealing structural homology with canonical 5'-> 3' DNA polymerases
      and adenylyl/guanylyl cyclases, whereas the closely related yeast homologue has
      been shown to function as a tRNA(HIS) guanyltransferase. SUMMARY: IHG-1 is a
      transcript up-regulated in renal cells exposed to high glucose, in animal models
      of renal fibrosis and in human diabetic nephropathy. IHG-1 encodes a
      mitochondrial protein that amplifies fibrotic responses to TGF-beta1 and promotes
      mitochondrial biogenesis. Investigation of the functional significance of the
      highly conserved domains of IHG-1 may lead to new therapeutic strategies.

PMID- 23165113
TI  - Effects of angiotensin II on kinase-mediated sodium and potassium transport in
      the distal nephron.
AB  - PURPOSE OF REVIEW: The aim is to review the recently reported effects of
      angiotensin II (Ang II) on sodium and potassium transport in the aldosterone
      sensitive distal nephron, including the signaling pathways between receptor and
      transporter, and the (patho)physiological implications of these findings. RECENT
      FINDINGS: Ang II can activate the sodium chloride cotransporter (NCC) through
      phosphorylation by Ste20-related, proline-alanine rich kinase (SPAK), an effect
      that is independent of aldosterone but dependent on with no lysine kinase 4
      (WNK4). A low-sodium diet (high Ang II) activates NCC, whereas a high-potassium
      diet (low Ang II) inhibits NCC. NCC activation also contributes to Ang-II
      mediated hypertension. Ang II also activates the epithelial sodium channel (ENaC)
      additively to aldosterone, and this effect appears to be mediated through protein
      kinase C and superoxide generation by nicotinamide adenine dinucleotide phosphate
      oxidase. While aldosterone activates the renal outer medullary potassium channel
      (ROMK), this channel is inhibited by Ang II. The key kinase responsible for this
      effect is c-Src, which phosphorylates ROMK and leaves WNK4 unphosphorylated to
      further inhibit ROMK. SUMMARY: The effects of Ang II on NCC, ENaC, and ROMK help
      explain the renal response to hypovolemia which is to conserve both sodium and
      potassium. Pathophysiologically, Ang-II-induced activation of NCC appears to
      contribute to salt-sensitive hypertension.

PMID- 23165114
TI  - Electron transparent graphene windows for environmental scanning electron
      microscopy in liquids and dense gases.
AB  - Due to its ultrahigh electron transmissivity in a wide electron energy range,
      molecular impermeability, high electrical conductivity and excellent mechanical
      stiffness, suspended graphene membranes appear to be a nearly ideal window
      material for in situ (in vivo) environmental electron microscopy of nano- and
      mesoscopic objects (including bio-medical samples) immersed in liquids and/or in
      dense gaseous media. In this paper, taking advantage of a small modification of
      the graphene transfer protocol onto metallic and SiN supporting orifices,
      reusable environmental cells with exchangeable graphene windows have been
      designed. Using colloidal gold nanoparticles (50 nm) dispersed in water as model
      objects for scanning electron microscopy in liquids as proof of concept,
      different conditions for imaging through the graphene membrane were tested.
      Limiting factors for electron microscopy in liquids, such as electron beam
      induced water radiolysis and damage of the graphene membrane at high electron
      doses, are discussed.

PMID- 23165115
TI  - A TaqMan-based real time PCR assay for specific detection and quantification of
      Xylella fastidiosa strains causing bacterial leaf scorch in oleander.
AB  - A TaqMan-based real-time PCR assay was developed for specific detection of
      strains of X. fastidiosa causing oleander leaf scorch. The assay uses primers WG
      OLS-F1 and WG-OLS-R1 and the fluorescent probe WG-OLS-P1, designed based on
      unique sequences found only in the genome of oleander strain Ann1. The assay is
      specific, allowing detection of only oleander-infecting strains, not other
      strains of X. fastidiosa nor other plant-associated bacteria tested. The assay is
      also sensitive, with a detection limit of 10.4fg DNA of X. fastidiosa per
      reaction in vitro and in planta. The assay can also be applied to detect low
      numbers of X. fastidiosa in insect samples, or further developed into a multiplex
      real-time PCR assay to simultaneously detect and distinguish diverse strains of
      X. fastidiosa that may occupy the same hosts or insect vectors. Specific and
      sensitive detection and quantification of oleander strains of X. fastidiosa
      should be useful for disease diagnosis, epidemiological studies, management of
      oleander leaf scorch disease, and resistance screening for oleander shrubs.

PMID- 23165116
TI  - Pax2+ astrocytes in the fish optic nerve head after optic nerve crush.
AB  - The transcription factor Pax2 actively participates in the development of the
      vertebrate visual system. In adults, Pax2 expression persists in a subpopulation
      of Muller cells and/or astrocytes in the retina and optic nerve head (ONH),
      although its function remains elusive. In a previous work we showed that the pax2
      gene expression is modified and the Pax2(+) astrocyte population in the ONH
      strongly reacted during the regeneration of the retina after a lesion in
      goldfish. In the present work we have analyzed Pax2 expression in the goldfish
      ONH after optic nerve (ON) crush. At one week post-injury, when the regenerating
      axons arrive at the ONH, the pax2 gene expression level increases as well as the
      number of Pax2(+) astrocytes in this region. These Pax2(+) astrocytes show a
      higher number of Cytokeratin (Ck)(+)/GFAP(+) processes compared with control
      animals. In contrast, a different S100(+) astrocyte population is not modified
      and persists similar to that of controls. Furthermore, we find a ring that
      surrounds the posterior ONH that is formed by highly reactive astrocytes,
      positive to Pax2, GFAP, Ck, S100, GS and ZO1. In this region we also find a
      source of new astrocytes Pax2(+)/PCNA(+) that is activated after the injury. We
      conclude that Pax2(+) astrocytes constitute a subpopulation of ONH astrocytes
      that strongly reacts after ON crush and supports our previous results obtained
      after retina regeneration. Altogether, this suggests that pax2 gene expression
      and Pax2(+) astrocytes are probably directly involved in the process of axonal
      regeneration.

PMID- 23165117
TI  - Separable processes before, during, and after the N400 elicited by previously
      inferred and new information: evidence from time-frequency decompositions.
AB  - Successful comprehension during reading often requires inferring information not
      explicitly presented. This information is readily accessible when subsequently
      encountered, and a neural correlate of this is an attenuation of the N400 event
      related potential (ERP). We used ERPs and time-frequency (TF) analysis to
      investigate neural correlates of processing inferred information after a causal
      coherence inference had been generated during text comprehension. Participants
      read short texts, some of which promoted inference generation. After each text,
      they performed lexical decisions to target words that were unrelated or inference
      related to the preceding text. Consistent with previous findings, inference
      related words elicited an attenuated N400 relative to unrelated words. TF
      analyses revealed unique contributions to the N400 from activity occurring at 1-6
      Hz (theta) and 0-2 Hz (delta), supporting the view that multiple, sequential
      processes underlie the N400.

PMID- 23165118
TI  - The effects of bilateral common carotid artery occlusion on expression of
      peripherin and choline acetyltransferase activity in C57BL/6 mice.
AB  - Peripherin is a 57-kDa type III neuronal intermediate filament protein that
      appears to play a role in neurite elongation during development and axonal
      regeneration. Its role in the pathogenesis of cognitive deficits caused by
      cerebral ischemia is unknown. The purpose of this study was to investigate the
      location and level of peripherin expression in the central nervous system in
      response to transient global cerebral ischemia, and the resultant effect of
      peripherin expression on the cholinergic neurons and Choline acetyltransferase
      (ChAT) activity in this mouse model of ischemia. Transient global cerebral
      ischemia was induced in C57BL/6 mice by 20-min bilateral common carotid artery
      occlusion (BCCAO) with microclips. The resulting impairment of spatial learning
      and memory was investigated by Morris water maze testing. Peripherin expression
      was evaluated by immunostaining and Western Blot assay of brain sections.
      Peripherin expression increased in neurons of the cortex, hippocampus, and
      thalamus after BCCAO. By double immunofluorescence staining, neurons showed a
      cytoplasmic co-localization of peripherin and MAP-2, but not of peripherin and
      GFAP. ChAT activity was determined spectrophotometrically using the assay kit.
      There was significantly decreased ChAT activity in the cerebral cortex,
      hippocampus and thalamus in mice of the BCCAO group (p<0.05), compared with the
      sham group. After BCCAO, peripherin overexpression was significantly correlated
      with reduction in ChAT activity (r=-0.929; p<0.01), spatial learning and memory
      were impaired, and peripherin expression was induced in neurons but not
      astrocytes. Thus, peripherin appears to be a participant in learning and memory
      impairment in mice.

PMID- 23165119
TI  - Metabotropic glutamate receptor 5 (mGluR5) regulates proliferation and
      differentiation of neuronal progenitors in the developmental hippocampus.
AB  - Metabotropic glutamate receptor 5 (mGluR5) is involved in neural stem cell self
      renewal, proliferation, differentiation and survival. In this study, we aimed to
      further determine the role of mGluR5 in the development of hippocampus using
      mGluR5 deficit (mGluR5(-/-)) and wild type (mGluR5(+/+)) mice at different
      developmental ages. We showed that the number of BrdU, NeuroD and DCX
      immunopositive cells was reduced significantly in mGluR5(-/-) than in mGluR5(+/+)
      mice from postnatal 7 days (P7) to P28, but not at P60. The length and intensity
      of DCX immunopositive apical dendrites in the dentate gyrus of mGluR5(-/-) mice
      were much shorter and lower than in mGluR5(+/+) mice respectively at P14, P21 and
      P28. NeuN immunostaining indicated an accelerated maturation of hippocampal
      neurons in mGluR5(-/-) mice. When mGluR5(+/+) mice were treated with 2-methyl-6
      (phenylethynyl) pyridine (MPEP), a selective antagonist of mGluR5, decreased
      proliferation of progenitor cells was observed in the hippocampus at early
      postnatal developmental stages. At P14, there were more BrdU(+) cells in the
      stratum granulosum and subgranular layer of the dentate gyrus in mGluR5(+/+) than
      in mGluR5(-/-) mice, but the percentage of BrdU(+)+NeuroD(+)/BrdU(+) in the
      dentate gyrus did not change significantly between the two genotypes of mice.
      Western Blot study suggested that programmed neuronal death was p53-dependent
      apoptosis in the developmental hippocampus in mGluR5(+/+) mice.

PMID- 23165120
TI  - Event-related potential evidence of accessing gender stereotypes to aid source
      monitoring.
AB  - Source memory for the speaker's voice (male or female) was investigated when
      semantic knowledge (gender stereotypes) could and could not inform the episodic
      source judgment while event-related potentials (ERPs) were recorded. Source
      accuracy was greater and response times were faster when stereotypes could
      predict the speaker's voice at test. Recollection supported source judgments in
      both conditions as indicated by significant parietal "old/new" ERP effects (500
      800ms). Prototypical late ERP effects (the right frontal "old/new" effect and the
      late posterior negativity, LPN) were evident when source judgment was based
      solely on episodic memory. However, these two late ERP effects were diminished
      and a novel, frontal-negative ERP with left-central topography was observed when
      stereotypes aided source judgments. This pattern of ERP activity likely reflects
      activation of left frontal or left temporal lobes when semantic knowledge, in the
      form of a gender stereotype, is accessed to inform the episodic source judgment.

PMID- 23165121
TI  - Symptomatic duodenal Crohn's disease: is strictureplasty the right choice?
AB  - Primary duodenal localization of Crohn's disease (CD) is rare. Medical therapy
      can control symptoms, but surgery is required when progressive obstructive
      symptoms occur. Surgical options include bypass, resection, or strictureplasty,
      but it is still not clear which should be the treatment of choice. Reviewing the
      medical records of 1253 patients undergoing surgery for CD between January 1986
      and December 2011 at the Digestive Surgery Unit of the Department of Clinical
      Physiopathology of the University of Florence, 10 patients (6 males and 4
      females) underwent operations for duodenal CD. Four patients had only a duodenal
      localization, 6 patients had synchronous involvement of other intestinal tracts.
      Strictures were distributed in all the duodenal portions: in 7 patients there
      were single lesions, in 3 patients there were multiple lesions. Eight patients
      were treated with strictureplasty: 5 with the Heineke-Mikulicz technique, 2 with
      Jaboulay, and 1 with a pedunculated jejunal patch. Two patients were treated with
      resection: one with a B2 gastro-duodenal resection, and 1 with a duodenal-jejunal
      resection and an end to side duodeno-jejunal anastomosis. Follow up of the
      patients was from 2 to 18 years. No recurrence of duodenal CD was observed in the
      2 patients treated with resection, while 2 of the 8 patients treated with
      strictureplasty had a recurrence. In our experience, strictureplasty is indicated
      when less than 2 strictures are present in the 2nd or 3rd duodenal portion. In
      cases with multiple strictures localized in the 1st or the distal duodenal
      portion, resection is preferable.

PMID- 23165122
TI  - Refractory chronic cough: new perspectives in diagnosis and treatment.
AB  - In patients with chronic cough, nearly 40% of the population does not experience
      definitive improvement of their cough despite correctly applying the anatomic
      diagnosis. In many of these patients with refractory cough, laryngeal symptoms
      are frequent. The region of the larynx/pharynx is configured as a bridge between
      the esophagus and the upper and lower respiratory tract. The association of
      reflux in patients with chronic cough and symptoms such as globus pharyngis,
      itchiness or the need to clear one's throat have recently been given attention
      due to the possibility of joint therapeutic intervention of the gastroesophageal
      reflux and larynx, both with new medications as well as with laryngeal
      rehabilitation therapies, with observed benefits in the disappearance of chronic
      cough in cases that had been previously labeled as refractory.

PMID- 23165125
TI  - Urological cancer. The benefits of intermittent androgen-deprivation therapy.
AB  - The large randomized study by Crook et al. demonstrated that intermittent
      administration of androgen deprivation therapy should be considered the standard
      of care when patients with moderate and well-differentiated localized prostate
      cancer are treated for rising PSA levels after definitive radiotherapy.

PMID- 23165124
TI  - Image-guided radiotherapy: from current concept to future perspectives.
AB  - Radiotherapy is a highly effective, targeted therapy for the management of
      cancer. Technological innovations have enabled the direct integration of imaging
      technology into the radiation treatment device to increase the precision and
      accuracy of radiation delivery. As well as addressing a clinical need to better
      control the placement of the dose within the body, image-guided radiotherapy has
      enabled innovators in the field to accelerate their exploration of a number of
      different paradigms of radiation delivery, including toxicity reduction, dose
      escalation, hypofractionation, voxelization, and adaptation. Although these
      approaches are already innovative trends in radiation oncology, it is anticipated
      that they will work synergistically with other innovations in cancer management
      (including biomarker strategies, novel systemic and local therapies) as part of
      the broader goal of personalized cancer medicine. This Review discusses the
      rationale for adopting image-guidance approaches in radiotherapy, and the
      technology for achieving precision and accuracy in the context of different
      paradigms within the evolving radiation oncology practice. It also examines
      exciting advances in radiotherapy technology that suggest a convergence of
      radiotherapy practice in which patient-specific radiotherapy treatment courses
      are one of the most personalized forms of intervention in cancer medicine.

PMID- 23165126
TI  - A multilevel approach for assessing the variability of hepatitis C prevalence in
      injection drug users by their gathering places.
AB  - OBJECTIVES: The aim of this study was to investigate the variation in hepatitis C
      virus (HCV) prevalence in injection drug users (IDUs) by their gathering places,
      using a multilevel approach. METHODS: IDUs recruited from their gathering places
      were invited to respond to a questionnaire on demographics, drug use history,
      injection behaviors, and methadone treatment. Dried blood spots were collected
      for HCV antibody testing by ELISA. Factors associated with the anti-HCV test
      result were explored by linear logistic regression, followed by the evaluation of
      heterogeneity between gathering places by multilevel analysis. RESULTS: A total
      of 622 respondents from 19 gathering places in Hong Kong, recruited between
      August and September 2011, were evaluated. Anti-HCV seroprevalence was 81.7% (95%
      confidence interval 78.6-84.7%), ranging from 67% to 100% by gathering place. HCV
      infection was associated with current practice of injection, needle-sharing, and
      midazolam injection. On multilevel analysis, there was a modest but significant
      variation in HCV antibody prevalence by gathering place, adjusted by midazolam
      injection (adjusted odds ratio (AOR) 3.91) and current injection (AOR 2.88) or
      injection over a long duration (AOR 3.17). CONCLUSIONS: There was heterogeneity
      in HCV antibody prevalence in IDUs by gathering place, while the influence of
      injection behaviors varied, suggesting interactivity between factors at the
      individual and group levels.

PMID- 23165127
TI  - Disappearance of 6-acetylmorphine, morphine and codeine from human scalp hair
      after discontinuation of opiate abuse.
AB  - Opiates continue to be used at high rates in East and Southeast Asia. Hair
      analysis for drugs of abuse has been developed into a powerful and widely used
      tool in forensic and clinical toxicology. Specifically, testing the proximal
      segment of scalp hair to confirm morphine (MOR) positive urine samples could
      solve the poppy seed problem. Human scalp hair grows approximately 1cm per month
      and can therefore reflect a retrospective timeline of drug exposure. This study
      is the first to investigate the disappearance of 6-acetylmorphine (6-AM), MOR and
      codeine (COD) from human scalp hair after the discontinuation of drug use. Thirty
      two healthy women (ages 21-51 years) with a known history of heroin abuse, who
      went to a rehabilitation centre and ceased consuming heroin (for 4-5 months),
      were recruited into the study. A pharmacokinetic analysis in seven individual
      hair segments was performed using a first-order kinetic. Assuming a rate of hair
      growth of 1cm/month, the mean hair elimination half-lives of 6-AM, MOR and COD
      were 0.88 months (95% CI, 0.74-1.03), 0.73 months (95% CI, 0.64-0.81), and 0.61
      months (95% CI, 0.54-0.69), respectively. Our results suggest that to evaluate
      the discontinuation of opiate abuse after a 6-month period of abstinence, the
      results from a 3-cm proximal hair segment should be free of 6-AM at the proposed
      0.2 ng/mg cutoff level. This finding should become the basis for the
      interpretation of results from segmental hair analyses in the evaluation of drug
      abstinence.

PMID- 23165129
TI  - Keeping practice knowledge current: part 1.
AB  - Today's fast-paced healthcare environment can make it challenging for nurse
      practitioners (NPs) to keep abreast of information they need to practice
      effectively. To make the task easier, NPs should set up a system to capture
      relevant information and evaluate it for applicability to clinical practice.

PMID- 23165128
TI  - Magnetic properties of Mn-doped Ge46 and Ba8Ge46 clathrates.
AB  - We present  a detailed study of the magnetic properties of unique cluster
      assembled solids, namely Mn-doped Ge(46) and Ba(8)Ge(46) clathrates using density
      functional theory. We find that ferromagnetic ground states may be realized in
      both compounds when doped with Mn. In Mn(2)Ge(44), ferromagnetism is driven by
      hybridization-induced negative exchange splitting, a generic mechanism operating
      in many diluted magnetic semiconductors. However, for Mn-doped Ba(8)Ge(46)
      clathrates incorporation of conduction electrons via Ba encapsulation results in
      RKKY-like magnetic interactions between the Mn ions. We show that our results are
      consistent with the major experimental observations for this system.

PMID- 23165123
TI  - Predicting outcomes in radiation oncology--multifactorial decision support
      systems.
AB  - With the emergence of individualized medicine and the increasing amount and
      complexity of available medical data, a growing need exists for the development
      of clinical decision-support systems based on prediction models of treatment
      outcome. In radiation oncology, these models combine both predictive and
      prognostic data factors from clinical, imaging, molecular and other sources to
      achieve the highest accuracy to predict tumour response and follow-up event
      rates. In this Review, we provide an overview of the factors that are correlated
      with outcome-including survival, recurrence patterns and toxicity-in radiation
      oncology and discuss the methodology behind the development of prediction models,
      which is a multistage process. Even after initial development and clinical
      introduction, a truly useful predictive model will be continuously re-evaluated
      on different patient datasets from different regions to ensure its population
      specific strength. In the future, validated decision-support systems will be
      fully integrated in the clinic, with data and knowledge being shared in a
      standardized, instant and global manner.

PMID- 23165130
TI  - A primer on Medicaid and its expansion in 2014.

PMID- 23165131
TI  - Mirabegron for overactive bladder.

PMID- 23165134
TI  - STI screening and treatment in pregnancy.
AB  - Nurse practitioners provide care for pregnant women with sexually transmitted
      infections. This article discusses the latest guidelines for treatment of
      sexually transmitted infections in pregnant women and provides recommendations
      for screening, treatment, prophylaxis, and follow-up.

PMID- 23165135
TI  - The face of lupus.
AB  - Systemic lupus erythematosus--a chronic, complex autoimmune disease without a
      definitive diagnostic test--often requires burdensome procedures to confirm
      diagnosis. Nurse practitioners must understand lupus' clinical and serologic
      manifestations to make a diagnosis; some cases may not be identified using only
      the American College of Rheumatology's criteria.

PMID- 23165136
TI  - Dizziness, vertigo, and presyncope: what's the difference?
AB  - Dizziness is a general term used to express subjective patient complaints related
      to changes in sensation, movement, perception, or consciousness. There are four
      types of dizziness: vertigo, disequilibrium, presyncope/syncope, and dizziness as
      a result of psychological disturbances. Differentiating the type of dizziness
      will assist in the course of the evaluation.

PMID- 23165138
TI  - Identification and utility of innate immune system evasion mechanisms of ASFV.
AB  - The interferon (IFN) system is an early innate anti-virus host defense mechanism
      that takes place shortly after entry of the pathogen and long before the onset of
      adaptive immunity. Thus, African swine fever virus (ASFV), as an acute and
      persistent virus in pigs, is predicted to have evolved multiple genes for the
      manipulation and evasion of interferon. Although, ASFV is known to interfere with
      signaling pathways controlling the transcription of cytokines, surprisingly no
      individual virus gene manipulating the induction or impact of IFN has been
      described. Since an initial bioinformatics search of the ASFV genome failed to
      identify potential antagonists of the IFN response, our strategy was to
      functionally screen early expressed, "unassigned" ASFV genes without existing
      homologies, particularly from MGFs 360 and 530, in luciferase reporter assays for
      their inhibition of the induction and impact of IFN. Specifically, we used
      reporter plasmids containing the luciferase gene under the control of: (1) the
      IFN-beta promoter, to screen for inhibition of induction of type I IFN stimulated
      by the addition of Poly(I:C); (2) the ISRE DNA elements, to screen for the
      inhibition of the impact of type I IFN; and (3) the GAS DNA elements to screen
      for the inhibition of the impact of type II IFN. Our initial experiments revealed
      six ASFV genes inhibiting one or more of the three luciferase assays. From these,
      we have selected a total of 3 genes for presentation. The ASFV A276R gene from
      MGF360 inhibited the induction of IFN-beta via both the TLR3 and the cytosolic
      pathways, targeting IRF3, but not IRF7 or NF-kappaB. The ASFV A528R inhibited the
      induction of both NF-kappaB and IRF3 branches of the type I IFN induction
      signaling pathway and the impact of IFN response via both IFN type I and type II
      stimulation. The ASFV I329L gene is a functional viral TLR3 homologue inhibiting
      the induction of IFN at the level of TRIF. Thus, these genes reduce the IFN
      response by targeting different intracellular signaling intermediates. Their
      deletion from wild type virus may strengthen the host interferon response and so
      provide an attenuated form with more restricted virus spread after the initial
      infection, perhaps "buying" sufficient time to allow the development of a
      protective adaptive immune response. The demonstration of multiple ASFV genes for
      the evasion of IFN responses will demand technology to construct viruses with
      multiple gene deletions. An alternative would be a multigene DNA vaccine.
      Finally, our work clearly demonstrates that unassigned viral genes may be viewed
      as a repository of host evasion strategies, only identifiable through functional
      assays. These may be considered to be "ready-made tools" for the experimental
      manipulation of cell biology and immune responses in health and disease and, as
      proof of concept, we have constructed a T-cell restricted transgenic mouse
      expressing the ASFV gene A238L, a dual inhibitor of NF-kappaB and NFAT
      activation. The resulting T cell restricted A238L transgenic mice developed a
      lymphoma with a phenotype reminiscent of some acute lymphoblastic lymphomas. In
      contrast, transgenic mice similarly expressing a mutant A238L solely inhibiting
      transcription mediated by NF-kappaB were indistinguishable from wild type mice,
      suggesting a transgene-NFAT-dependent transformation. Elucidation of the
      molecular events associated with the development of this virus host evasion
      molecule induced tumor may clarify some mechanisms of tumorigenesis in general,
      and in the development of T cell acute lymphoblastic leukemia in particular.

PMID- 23165139
TI  - Analysis of the pX region of bovine leukemia virus in different clinical stages
      of Enzootic Bovine Leukemia in Argentine Holstein cattle.
AB  - Bovine leukemia virus (BLV) infection in cattle causes Enzootic Bovine Leukemia
      (EBL). About 30% of infected cattle develop persistent lymphocytosis (PL), a 0.1
      5% develops tumors, and a 70% remains asymptomatic in an aleukemic stage (AL).
      Regulatory genes of BLV (Tax, Rex, R3 and G4) are located in a region known as
      pX(BLV). The variability of those genes had been postulated with the progression
      of the disease. The aim of this work was to compare the wild-type proviral
      pX(BLV) region at different stages of BLV natural infected cattle from Argentine
      Holstein. Pairs of primers were designed to amplify the proviral pX region of 12
      cattle by PCR, and products were then sequenced, aligned and compared both with
      each other and with the reference sequence. Results show a divergence percentage
      from 0 to 6.1 for the Tax gene, from 0 to 9.4% for the Rex gene, from 0 to 12.1%
      for the R3 gene and finally from 0 to 6.5% for the G4 gene. Results obtained with
      hierarchical clustering showed two clusters well differentiated, where the
      members of each cluster are cattle that had tumor, PL and AL, not allowing
      differentiate those two cluster by clinical stage.

PMID- 23165140
TI  - Radiolabelling and PET brain imaging of the alpha1-adrenoceptor antagonist Lu
      AE43936.
AB  - Cerebral alpha1-adrenoceptors are a common target for many antipsychotic drugs.
      Thus, access to positron emission tomography (PET) brain imaging of alpha1
      adrenoceptors could make important contributions to the understanding of
      psychotic disorders as well as to the pharmacokinetics and occupancy of drugs
      targeting the alpha1-adrenoceptors. However, so far no suitable PET radioligand
      has been developed for brain imaging of alpha1-adrenoceptors. Here, we report the
      synthesis of both enantiomers of the desmethyl precursors of the high affinity
      alpha1-adrenoceptor ligand (1). The two enantiomers of 1 were subsequently [11C]
      radiolabelled and evaluated for brain uptake and binding by PET imaging in Danish
      Landrace pigs. (S)-[11C]-1 and (R)-[11C]-1 showed very limited brain uptake. Pre
      treatment with cyclosporine A (CsA) resulted in a large increase in brain uptake,
      indicating that (R)-[11C]-1 is a substrate for active efflux-transporters. This
      was confirmed in Madin Darby canine kidney (MDCK) cells overexpressing
      permeability glycoprotein (Pgp). In conclusion, the limited brain uptake of both
      (S)-[11C]-1 and (R)-[11C]-1 in the pig brain necessitates the search for
      alternative radioligands for in vivo PET brain imaging of alpha1-adrenoceptors.

PMID- 23165141
TI  - Psychogenic nonepileptic seizures and chronic pain: a retrospective case
      controlled study.
AB  - PURPOSE: Psychogenic nonepileptic seizures (PNES) can be challenging to diagnose,
      but certain clinical features can help to distinguish PNES from epileptic
      seizures. The purpose of this study is to assess chronic pain and prescribed pain
      medication use in PNES patients. METHODS: A case-controlled, retrospective
      analysis was performed examining pain medication use in 85 PNES patients versus
      an active control group of 85 patients with idiopathic generalized epilepsy
      (IGE). RESULTS: Chronic pain was more frequent among PNES patients (N=40) than
      active controls (N=10) (p<0.0001). Reported use of prescription pain medication
      was higher among PNES patients (N=20) versus active controls (N=6) (p=0.0048).
      The Positive Predictive Value of prescription pain medications for PNES patients
      was 76.9%. Opioid use in the PNES population was higher compared with active
      controls (p=0.0096). When excluding patients with a dual diagnosis of PNES and
      epilepsy from the latter two analyses and comparing these results to those that
      included this patient population, no statistically significant difference in
      results was found. CONCLUSIONS: Patients with PNES are more likely than those
      with IGE to report chronic pain disorders. A history of chronic pain and opioid
      use among patients with seizures raises the possibility of PNES. Among patients
      with PNES and chronic pain, a psychogenic etiology for pain and non-opiate pain
      management strategies should be considered.

PMID- 23165142
TI  - Tumor-cell-derived microvesicles as carriers of molecular information in cancer.
AB  - PURPOSE OF REVIEW: Exosomes and microvesicles are secreted particles of 30-200 
      nm in diameter, delimited by a lipid bilayer and containing a wide range of
      membrane-bound or free proteins and nucleic acids (in particular mRNA and miRNA).
      Here, we review the properties of tumor-cell-derived microvesicles as carriers of
      molecular information in relation to cancer progression and promotion of
      metastasis. RECENT FINDINGS: Microvesicles from tumor cells operate as signaling
      platforms that diffuse in the extracellular space to target cells in the
      microenvironment, modulating the interactions of tumor cells with stromal,
      inflammatory, dendritic, immune or vascular cells and priming the formation of
      the metastatic niche. SUMMARY: Because of their stability, exosomes and
      microvesicles can be retrieved in bodily fluids as biomarkers for cancer
      detection and monitoring. They offer a range of molecular targets for controlling
      cell-cell interactions during invasion and metastasis.

PMID- 23165143
TI  - Lessons from tumor reversion for cancer treatment.
AB  - PURPOSE OF REVIEW: Tumor reversion is the biological process by which highly
      tumorigenic cells lose at great extent or entirely their malignant phenotype. The
      purpose of our research is to understand the molecular program of tumor reversion
      and its clinical application. We first established biological models of
      reversion, which was done by deriving revertant cells from different tumors.
      Secondly, the molecular program that could override the malignant phenotype was
      assessed. Differential gene-expression profiling showed that at least 300 genes
      are implicated in this reversion process such as SIAH-1, PS1, TSAP6, and, most
      importantly, translationally controlled tumor protein (TPT1/TCTP). Decreasing
      TPT1/TCTP is key in reprogramming malignant cells, including cancer stem cells.
      RECENT FINDINGS: Recent findings indicate that TPT1/TCTP regulates the P53-MDM2
      Numb axis. Notably, TPT1/TCTP and p53 are implicated in a reciprocal negative
      feedback loop. TPT1/TCTP is a highly significant prognostic factor in breast
      cancer. Sertraline and thioridazine interfere with this repressive feedback by
      targeting directly TPT1/TCTP and inhibiting its binding to MDM2, restoring
      wildtype p53 function. Combining sertraline with classical drugs such as Ara-C in
      acute myeloid leukemia may be also beneficial. SUMMARY: In this review, we
      discuss some of these reversion pathways and how this approach could open a new
      route to cancer treatment.

PMID- 23165145
TI  - 1alpha,25-Dihydroxyvitamin D3 reduces several types of UV-induced DNA damage and
      contributes to photoprotection.
AB  - Vitamin D production requires UVB. In turn, we have shown that vitamin D
      compounds reduce UV-induced damage, including inflammation, sunburn, thymine
      dimers, the most frequent type of cyclobutane pyrimidine dimer,
      immunosuppression, and photocarcinogenesis. Our previous studies have shown most
      of the photoprotective effects by 1alpha,25-dihydroxyvitamin D3 (1,25(OH)2D3)
      occurred through the nongenomic pathway because similar protection was seen with
      an analog, 1alpha,25-dihydroxylumistrol3 (JN), which has little ability to alter
      gene expression and also because a nongenomic antagonist of 1,25(OH)2D3 abolished
      protection. In the current study, we tested whether this photoprotective effect
      would extend to other types of DNA damage, and whether this could be demonstrated
      in human ex vivo skin, as this model would be suited to pre-clinical testing of
      topical formulations for photoprotection. In particular, using skin explants, we
      examined a time course for thymine dimers (TDs), the most abundant DNA
      photolesion, as well as 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG), which is a
      mutagenic DNA base lesion arising from UV-induced oxidative stress, and 8
      nitroguanosine (8-NG). Nitric oxide products, known markers for chronic
      inflammation and carcinogenesis, are also induced by UV. This study showed that
      1,25(OH)2D3 significantly reduced TD and 8-NG as early as 30min post UV, and 8
      oxodG at 3h post UV, confirming the photoprotective effect of 1,25(OH)2D3 against
      DNA photoproducts in human skin explants. At least in part, the mechanism of
      photoprotection by 1,25(OH)2D3 is likely to be through the reduction of reactive
      nitrogen species and the subsequent reduction in oxidative and nitrosative
      damage. This article is part of a Special Issue entitled 'Vitamin D Workshop'.

PMID- 23165146
TI  - The novel purification and biochemical characterization of a reversible
      CYP24A1:adrenodoxin complex.
AB  - Novel paradigms for CYP24A1 inhibitor development are needed to circumvent
      existing efficacy and toxicity issues related to human therapeutics in this
      class. We hypothesize that improved structural knowledge of CYP24A1 in complex
      with natural substrates, inhibitors and/or its redox partner protein, adrenodoxin
      (Adx) is required to facilitate the next generation of CYP24A1 inhibitor design.
      To this end, we have developed truncated expression constructs for both rat
      CYP24A1 (Delta51) and bovine Adx (Delta108), which allow us to purify a stable
      and reversible state of the CYP24A1:Adx complex, for use in ongoing X-ray
      crystallographic studies. Spectral characterization of the reversible complex
      revealed that Adx binding enhanced the stability of the enzyme-substrate complex,
      despite lowering the ligand binding affinity of the free enzyme, for 1,25(OH)2D2,
      over 9-fold. Truncation of CYP24A1's flexible N-terminus (Delta51) improved the
      enzyme's ability to recruit substrate, without altering Adx's ability to
      stabilize the ligand-bound form. We also found that several common
      crystallization detergents, including CHAPS, inhibit ligand binding to the
      CYP24A1:Adx complex at concentrations well below their reported critical micelle
      concentration (CMC) values. Ultimately, this research provides a useful platform
      and framework for the study of conformationally complex, membrane-protein
      complexes, in the ligand-bound state.

PMID- 23165147
TI  - Cardiac device-related endocarditis: 31-Years' experience.
AB  - BACKGROUND: Cardiac device-related endocarditis (CDE) is a major complication of
      the implantation of a pacemaker and defibrillator. The experience in a single
      high-volume tertiary center is reported. METHODS: Thirty one years (1980-2011) of
      cases of CDE were analyzed retrospectively and compared to overall insertion
      data; the clinical course and management strategies of these patients have been
      reviewed. RESULTS: A total of 23 cases (16 male, median age 72 years) were
      identified, 20 of these cases were determined at our institution where 5287
      procedures were performed (endocarditis rate 0.38%). Thirteen patients were
      determined to have a cardiac device pocket infection. Infection in 7 cases (30%)
      was caused by lead(s). However, in 16 cases (70%) both leads and the pocket of
      devices were the reason of infection. Median time was 13.5 months for
      presentation. Patients who had undergone the last procedure within 6 months were
      admitted earlier than those with longer post procedure time (p<0.05).
      Transesophageal echocardiography demonstrated lead vegetations in 13 of the 16
      cases (81%). Organisms were identified in 18 cases (78%)-78% Staphylococci (56%
      Staphylococcus aureus). Leads of the device were removed in 17 cases (74%); seven
      cases by percutaneous simple traction and 10 cases by sternotomy. Six major
      complications attributable to device-related endocarditis were observed: four
      deaths (mortality 17.4%); one splenic abscess requiring splenectomy; and one
      septic pulmonary embolism; median follow-up 49 months. CONCLUSION: A CDE
      endocarditis rate of 0.38% was demonstrated. It remains a rare but potentially
      lethal complication of device implantation.

PMID- 23165148
TI  - The current status of lipoprotein (a) in pregnancy: a literature review.
AB  - BACKGROUND AND PURPOSE: Lipoprotein (Lp) (a) is a neglected element of the blood
      lipid profile. It is now recognized as a determinant of coronary heart disease
      progression and its role in atherosclerosis and its ability to induce thrombosis
      make it potentially important in the course of normal and complicated
      pregnancies. Pregnancy involves a major transformation of metabolism to sustain
      fetal growth. Multiple studies have been conducted on Lp(a) in pregnancy, and it
      is timely to synthesize and evaluate this evidence. METHODS AND SUBJECTS: We
      reviewed the MEDLINE database for all articles published concerning "lipoprotein
      a" and "pregnancy" from May 2003 to May 2012. A previous comprehensive review
      assessed the literature up to May 2003. RESULTS: We critically analyzed 14
      studies detailing the effect of complications in pregnancy on Lp(a) profile, and
      subsequent pregnancy outcomes where available. Studies evaluating the normal
      metabolic response to pregnancy, pregnancies complicated by pre-eclampsia and
      intra-uterine growth restriction were reviewed. CONCLUSIONS: A substantial mass
      of data has accumulated describing Lp(a) changes in pregnancy. The diversity of
      study design limits the ability to draw broad-ranging conclusions, but brings
      into focus the important questions remaining, which we discuss.

PMID- 23165149
TI  - Extent of heart rate reduction during hospitalization using beta-blockers, not
      the achieved heart rate itself at discharge, predicts the clinical outcome in
      patients with acute heart failure syndromes.
AB  - AIM: It has been uncertain whether patients with acute heart failure syndromes
      (AHFSs) benefit from a lower heart rate (HR) itself or from treatment for heart
      failure (HF) that reduces sympathetic tone with consequent HR reduction (HRR).
      The present study investigated the influence of HRR during hospitalization on the
      prognosis of AHFS patients. METHODS AND RESULTS: In 421 AHFS patients, we
      analyzed the relationship between HRR during hospitalization and the prognosis
      after discharge. During a mean follow-up period of 1.9 years, 76 and 55 patients
      died or were re-hospitalized for HF, respectively. Although HR at discharge did
      not influence cardiac events (hazard ratio [HR]: 1.00 [95% CI; 0.99-1.02],
      p=0.22), the extent of HRR was a predictor of cardiac events (HR: 0.89 [0.84
      0.96], p<0.001). Kaplan-Meier analysis revealed that the cardiac event rate of
      the HRR-positive group (>= 27 bpm reduction of HR from 114 +/- 24 at admission to
      65 +/- 11 bpm at discharge) was significantly lower than that of the HRR-negative
      group (<= 26 bpm (=median value) reduction of HR from 74 +/- 14 to 71 +/- 14
      bpm). In the HRR-positive group, the cardiac event rate was significantly lower
      in patients receiving beta-blockers. Furthermore, the extent of HR change was an
      important predictor of cardiac events among other markers, compared with the
      change in systolic blood pressure or B-type natriuretic peptide. CONCLUSION: The
      HR itself at discharge was not associated with the prognosis, but the extent of
      HRR achieved by treatment of HF with beta-blockers was a strong predictor for the
      clinical outcome in AHFS patients.

PMID- 23165151
TI  - An intelligent anticorrosion coating based on pH-responsive supramolecular
      nanocontainers.
AB  - The hollow mesoporous silica nanoparticles (HMSNs), which have been used as the
      nanocontainers for the corrosion inhibitor, benzotriazole, were fabricated using
      the hard-template method. Alkaline-responsive HMSNs based on cucurbit[6]uril
      (CB[6])/bisammonium supramolecular complex and acid-responsive HMSNs based on
      alpha-cyclodextrin (alpha-CD)/aniline supramolecular complex, which operate in
      water, have been achieved and characterized by solid-state NMR, thermogravimetry
      analysis, scanning electron microscopy, transmission electron microscopy and N(2)
      adsorption-desorption analysis. The two elaborately designed nanocontainers show
      the pH-controlled encapsulation/release behaviors for benzotriazole molecules.
      Equal amounts of the alkaline- and acid-responsive nanocontainers were uniformly
      distributed in the hybrid zirconia-silica sol-gel coating and thus formed the
      intelligent anticorrosion coating. The self-healing property of AA2024 alloy
      coated with the intelligent anticorrosion coating is evaluated by electrochemical
      impedance spectroscopy (EIS). The sol-gel coating doped with the pH-responsive
      nanocontainers clearly demonstrates long-term corrosion protection performances
      when compared to the undoped sol-gel coating, which is attributed to the release
      of corrosion inhibitor from the nanocontainers after feeling the changes of
      environmental pH values near the corroded areas.

PMID- 23165152
TI  - Information and communication technology to support self-management of patients
      with mild acquired cognitive impairments: systematic review.
AB  - BACKGROUND: Mild acquired cognitive impairment (MACI) is a new term used to
      describe a subgroup of patients with mild cognitive impairment (MCI) who are
      expected to reach a stable cognitive level over time. This patient group is
      generally young and have acquired MCI from a head injury or mild stroke. Although
      the past decade has seen a large amount of research on how to use information and
      communication technology (ICT) to support self-management of patients with
      chronic diseases, MACI has not received much attention. Therefore, there is a
      lack of information about what tools have been created and evaluated that are
      suitable for self-management of MACI patients, and a lack of clear direction on
      how best to proceed with ICT tools to support self-management of MACI patients.
      OBJECTIVE: This paper aims to provide direction for further research and
      development of tools that can support health care professionals in assisting MACI
      patients with self-management. An overview of studies reporting on the design
      and/or evaluation of ICT tools for assisting MACI patients in self-management is
      presented. We also analyze the evidence of benefit provided by these tools, and
      how their functionality matches MACI patients' needs to determine areas of
      interest for further research and development. METHODS: A review of the existing
      literature about available assistive ICT tools for MACI patients was conducted
      using 8 different medical, scientific, engineering, and physiotherapy library
      databases. The functionality of tools was analyzed using an analytical framework
      based on the International Classification of Functioning, Disability and Health
      (ICF) and a subset of common and important problems for patients with MACI
      created by MACI experts in Sweden. RESULTS: A total of 55 search phrases applied
      in the 8 databases returned 5969 articles. After review, 7 articles met the
      inclusion criteria. Most articles reported case reports and exploratory research.
      Out of the 7 articles, 4 (57%) studies had less than 10 participants, 5 (71%)
      technologies were memory aids, and 6 studies were mobile technologies. All 7
      studies fit the profile for patients with MACI as described by our analytical
      framework. However, several areas in the framework important for meeting patient
      needs were not covered by the functionality in any of the ICT tools. CONCLUSIONS:
      This study shows a lack of ICT tools developed and evaluated for supporting self
      management of MACI patients. Our analytical framework was a valuable tool for
      providing an overview of how the functionality of these tools matched patient
      needs. There are a number of important areas for MACI patients that are not
      covered by the functionality of existing tools, such as support for interpersonal
      interactions and relationships. Further research on ICT tools to support self
      management for patients with MACI is needed.

PMID- 23165153
TI  - Pathophysiological roles of aldo-keto reductases (AKR1C1 and AKR1C3) in
      development of cisplatin resistance in human colon cancers.
AB  - Cisplatin (cis-diamminedichloroplatinum, CDDP) is widely used for treatment of
      patients with solid tumors formed in various organs including the lung, prostate
      and cervix, but is much less sensitive in colon and breast cancers. One major
      factor implicated in the ineffectiveness has been suggested to be acquisition of
      the CDDP resistance. Here, we established the CDDP-resistant phenotypes of human
      colon HCT15 cells by continuously exposing them to incremental concentrations of
      the drug, and monitored expressions of aldo-keto reductases (AKRs) 1A1, 1B1,
      1B10, 1C1, 1C2 and 1C3. Among the six AKRs, AKR1C1 and AKR1C3 are highly induced
      with the CDDP resistance. The resistance lowered the sensitivity toward cellular
      damages evoked by oxidative stress-derived aldehydes, 4-hydroxy-2-nonenal and 4
      oxo-2-nonenal that are detoxified by AKR1C1 and AKR1C3. Overexpression of AKR1C1
      or AKR1C3 in the parental HCT15 cells mitigated the cytotoxicity of the aldehydes
      and CDDP. Knockdown of both AKR1C1 and AKR1C3 in the resistant cells or treatment
      of the cells with specific inhibitors of the AKRs increased the sensitivity to
      CDDP toxicity. Thus, the two AKRs participate in the mechanism underlying the
      CDDP resistance probably via detoxification of the aldehydes resulting from
      enhanced oxidative stress. The resistant cells also showed an enhancement in
      proteolytic activity of proteasome accompanied by overexpression of its catalytic
      subunits (PSMbeta9 and PSMbeta10). Pretreatment of the resistant cells with a
      potent proteasome inhibitor Z-Leu-Leu-Leu-al augmented the CDDP sensitization
      elicited by the AKR inhibitors. Additionally, the treatment of the cells with Z
      Leu-Leu-Leu-al and the AKR inhibitors induced the expressions of the two AKRs and
      proteasome subunits. Collectively, these results suggest the involvement of up
      regulated AKR1C1, AKR1C3 and proteasome in CDDP resistance of colon cancers and
      support a chemotherapeutic role for their inhibitors.

PMID- 23165150
TI  - Regulation of pol III transcription by nutrient and stress signaling pathways.
AB  - Transcription by RNA polymerase III (pol III) is responsible for ~15% of total
      cellular transcription through the generation of small structured RNAs such as
      tRNA and 5S RNA. The coordinate synthesis of these molecules with ribosomal
      protein mRNAs and rRNA couples the production of ribosomes and their tRNA
      substrates and balances protein synthetic capacity with the growth requirements
      of the cell. Ribosome biogenesis in general and pol III transcription in
      particular is known to be regulated by nutrient availability, cell stress and
      cell cycle stage and is perturbed in pathological states. High throughput
      proteomic studies have catalogued modifications to pol III subunits, assembly,
      initiation and accessory factors but most of these modifications have yet to be
      linked to functional consequences. Here we review our current understanding of
      the major points of regulation in the pol III transcription apparatus, the
      targets of regulation and the signaling pathways known to regulate their
      function. This article is part of a Special Issue entitled: Transcription by Odd
      Pols.

PMID- 23165154
TI  - Three-month subchronic intramuscular toxicity study of rotigotine-loaded
      microspheres in Cynomolgus monkeys.
AB  - Continuous dopaminergic stimulation (CDS) is an important drug development
      strategy in the treatment of Parkinson's disease (PD). Rotigotine is a non
      ergoline D(3)/D(2)/D(1) dopamine receptor agonist for treating PD. As a new
      treatment option for CDS, rotigotine-loaded microspheres (RoMS), long-acting
      sustained-release microspheres with poly(lactide-co-glycolide) as drug carrier,
      are now being evaluated in clinical trial. In the present study, the subchronic
      toxicity in Cynomolgus monkeys has been characterized via intramuscular
      administration with RoMS at 0, 10, 40 and 160 mg/kg, weekly for 3 months with a 1
      month recovery period. The NOAEL was 10 mg/kg/week. One male at 160 mg/kg died
      from an extensive pulmonary embolism. The major toxicological effects were
      associated with dopamine agonist-related pharmacodynamic properties of rotigotine
      (e.g., hyperactivity and stereotype, decreased serum prolactin level) and foreign
      body removal reaction induced by poly(lactide-co-glycolide) and
      carboxymethycellulose sodium (e.g., increased mononuclear cells and neutrophils,
      thymus atrophy and vacuolar degeneration of adrenal cortex, foreign body
      granuloma with foam cells accumulation at injection sites and foam cells
      accumulation in spleen and multiple lymph sinuses). At the end of recovery
      period, above findings recovered to a normal level or to a certain degree except
      vacuolar degeneration of adrenal gland. RoMS has exhibited high safety on
      monkeys.

PMID- 23165155
TI  - In vitro combined cytotoxic effects of pesticide cocktails simultaneously found
      in the French diet.
AB  - Although human populations may be constantly exposed to complex pesticide
      mixtures through their diet, the human health risk of pesticide exposure is
      currently assessed on the basis of toxicity data on individual compounds. To
      investigate the combined toxic effects of pesticide cocktails previously
      identified in the French diet, we first studied the cytotoxicity induced by seven
      cocktails composed of two to six pesticides on human hepatic (HepG2) and colon
      (Caco-2) cell lines using the MTT and neutral red uptake assays. Secondly, we
      challenged to assess the combined effects of the two most cytotoxic cocktails by
      comparing the measured effects of the mixtures with the predictions based on
      additive effects on two concepts-independent action (IA) and concentration
      addition (CA). For the cocktail composed of dichlorodiphenyltrichloroethane (DDT)
      and dieldrin, the cytotoxicity of the equimolar cocktail proved greater than the
      additive effect estimated by the two concepts. Furthermore, apoptosis induction
      was higher in equimolar cocktail than predicted by summing the effects of DDT and
      dieldrin. Thus, some supra-additive toxicity was found in the DDT-dieldrin
      cocktail. Nevertheless, if IA and CA models could reveal combined effects of
      pesticide cocktails, an accurate evaluation remains challenging.

PMID- 23165156
TI  - The SFPT feels compelled to point out weaknesses in the paper by Seralini et al.
      (2012).

PMID- 23165158
TI  - Dynamical equations for time-ordered Green's functions: from the Keldysh time
      loop contour to equilibrium at finite and zero temperature.
AB  - We study the dynamical equation of the time-ordered Green's function at finite
      temperature. We show that the time-ordered Green's function obeys a conventional
      Dyson equation only at equilibrium and in the limit of zero temperature. In all
      other cases, i.e. finite temperature at equilibrium or non-equilibrium, the time
      ordered Green's function obeys instead a modified Dyson equation. The derivation
      of this result is obtained from the general formalism of the non-equilibrium
      Green's functions on the Keldysh time-loop contour. At equilibrium, our result is
      fully consistent with the Matsubara temperature Green's function formalism and
      also justifies rigorously the correction terms introduced in an ad hoc way with
      Hedin and Lundqvist. Our results show that one should use the appropriate
      dynamical equation for the time-ordered Green's function when working beyond the
      equilibrium zero-temperature limit.

PMID- 23165159
TI  - Diabetes: Add-on aliskiren has limited benefit.

PMID- 23165160
TI  - Therapy: An antibody therapy lowers LDL cholesterol levels.

PMID- 23165162
TI  - Bone: Risk of osteoporotic fractures in irritable bowel syndrome.

PMID- 23165161
TI  - Global obesity: trends, risk factors and policy implications.
AB  - The worldwide increase in obesity and related chronic diseases has largely been
      driven by global trade liberalization, economic growth and rapid urbanization.
      These factors continue to fuel dramatic changes in living environments, diets and
      lifestyles in ways that promote positive energy balance. Nutritional transitions
      in low-income and middle-income countries are typically characterized by
      increases in the consumption of animal fat and protein, refined grains, and added
      sugar. This change is coupled with reductions in physical activity owing to more
      mechanized and technologically driven lifestyles. Given the high costs of obesity
      and comorbidities in terms of health-care expenditure and quality of life,
      prevention strategies are paramount, particularly in low-income and middle-income
      countries that must manage coexisting infectious diseases and undernutrition in
      addition to the obesity epidemic. As countries become increasingly urbanized,
      undernutrition and obesity can exist side by side within the same country,
      community or household, which is a particular challenge for health systems with
      limited resources. Owing to the scope and complexity of the obesity epidemic,
      prevention strategies and policies across multiple levels are needed in order to
      have a measurable effect. Changes should include high-level global policies from
      the international community and coordinated efforts by governments,
      organizations, communities and individuals to positively influence behavioural
      change.

PMID- 23165163
TI  - Therapy: Thyroid hormone receptor agonists to reduce cholesterol levels?

PMID- 23165164
TI  - Selecting the best instruments to measure quality of end-of-life care and quality
      of dying in long term care.
AB  - OBJECTIVES: To compare available instruments and investigate which best measure
      the quality of end-of-life care (QOC) and quality of dying (QOD) in long term
      care settings, in terms of validity, reliability, and feasibility. DESIGN: Family
      and professional caregivers of long term care decedents completed postdeath
      interviews and questionnaires between November 2007 and April 2009. SETTING:
      Nursing home and residential care/assisted living settings in the United States
      and the Netherlands. PARTICIPANTS: Two hundred and sixty four families of
      decedents with (48%) and without (52%) dementia in the United States, and 70
      families and 103 professional caregivers of decedents with dementia in The
      Netherlands. MEASUREMENTS: Ten instruments to evaluate the QOC and QOD in long
      term care, an additional overall assessment of QOC/QOD, and an assessment of the
      perception of the relevance and ease of use of each instrument. Criteria for
      validity, reliability, and feasibility were set forth for good, intermediate, and
      poor performance. RESULTS: None of the instruments scored positively on all
      criteria. In both countries, of the QOC instruments, the End-of-Life in Dementia
      Satisfaction With Care (EOLD-SWC) best met the criteria, followed by the Family
      Assessment of Treatment at the End-of-Life Short Version, the Family Perception
      of Care Scale, and Family Perception of Physician-Family Caregiver Communication.
      Of the QOD instruments, the End-of-Life in Dementia-Comfort Assessment at Dying
      (EOLD-CAD) and Mini-Suffering State Examination (MSSE) met more of the criteria
      than others. The EOLD-CAD performed better on content and construct validity than
      the MSSE. The MSSE performed better on feasibility. CONCLUSION: We recommend the
      EOLD-SWC to measure QOC, and the EOLD-CAD and MSSE to measure QOD in populations
      with dementia and in mixed long term care populations of nursing home or
      residential care home/assisted living residents, because they performed best in
      both countries. Use of the same instruments allows for comparison of the results
      between studies.

PMID- 23165165
TI  - Mutant laboratory mice with abnormalities in hair follicle morphogenesis,
      cycling, and/or structure: an update.
AB  - Human hair disorders comprise a number of different types of alopecia, atrichia,
      hypotrichosis, distinct hair shaft disorders as well as hirsutism and
      hypertrichosis. Their causes vary from genodermatoses (e.g. hypotrichoses) via
      immunological disorders (e.g. alopecia areata, autoimmune cicatrical alopecias)
      to hormone-dependent abnormalities (e.g. androgenetic alopecia). A large number
      of spontaneous mouse mutants and genetically engineered mice develop
      abnormalities in hair follicle morphogenesis, cycling, and/or hair shaft
      formation, whose analysis has proven invaluable to define the molecular
      regulation of hair growth, ranging from hair follicle development, and cycling to
      hair shaft formation and stem cell biology. Also, the accumulating reports on
      hair phenotypes of mouse strains provide important pointers to better understand
      the molecular mechanisms underlying human hair growth disorders. Since numerous
      new mouse mutants with a hair phenotype have been reported since the publication
      of our earlier review on this matter a decade ago, we present here an updated,
      tabulated mini-review. The updated annotated tables list a wide selection of
      mouse mutants with hair growth abnormalities, classified into four categories:
      Mutations that affect hair follicle (1) morphogenesis, (2) cycling, (3)
      structure, and (4) mutations that induce extrafollicular events (for example
      immune system defects) resulting in secondary hair growth abnormalities. This
      synthesis is intended to provide a useful source of reference when studying the
      molecular controls of hair follicle growth and differentiation, and whenever the
      hair phenotypes of a newly generated mouse mutant need to be compared with
      existing ones.

PMID- 23165166
TI  - Association of melanogenesis genes with skin color variation among Japanese
      females.
AB  - BACKGROUND: Skin color mainly reflects pigmentation resulting from melanin.
      Although many of the detailed molecular mechanisms involved in melanin
      pigmentation are being revealed, little is understood about the genetic
      components responsible for variations in skin color within or between human
      populations. OBJECTIVE: To investigate the contribution of the melanogenesis
      genes to skin color variation in Japanese population. METHODS: We examined the
      association between 12 variants of four pigmentation-related genes (TYR, OCA2,
      SLC45A2, MC1R) and variations in the melanin index of 456 Japanese females using
      a multiple regression analysis. RESULTS: OCA2 A481T (p=6.18*10(-8)) and, OCA2
      H615R (p=5.72*10(-6)) were strongly associated with the melanin index. In
      addition, our results yielded evidence for a significant association in a
      combined analysis of males and females (OCA2 A481T p=2.1*10(-11), and OCA2 H615R
      p=1.0*10(-7)). Then five surviving variants including A481T, H615R, T387M in
      OCA2, D125Y in TYR, and T500P in SLC45A2, accounted for contribution to about 11%
      of the melanin index. CONCLUSION: The skin color analysis among Japanese was
      successfully carried out to determine the association with genetic components by
      using the melanin index as an objective indicator. We believe that a better
      understanding of the genetic basis of skin color variation will be valuable for
      elucidating the correlation of pigmentation phenotype with skin-cancer risk.

PMID- 23165167
TI  - pi-Core tailoring for new high performance thieno(bis)imide based n-type
      molecular semiconductors.
AB  - The synthesis and characterization of two thieno(bis)imide based n-type
      semiconductors with electron mobilities of up to 0.3 cm(2) V(-1) s(-1) are
      described. The relationships between the electronic features of the pi-inner core
      and the functional properties of the new materials are also discussed.

PMID- 23165168
TI  - Response to UVB radiation and oxidative stress of marine bacteria isolated from
      South Pacific Ocean and Mediterranean Sea.
AB  - Marine bacterial strains isolated from South Pacific and Mediterranean Sea were
      studied for their resistance to UVB radiation, their repair capacity under
      photoreactivating light, as well as their oxidative stress response using
      concentrated hydrogen peroxide (H(2)O(2)), as an oxidizer. A total of 30 marine
      bacteria were isolated from the hyper-oligotrophic waters of the South Pacific
      Gyre to the eutrophic waters of the Chilean coast during the BIOSOPE cruise
      (2004), and 10 strains from surface Mediterranean coastal waters. One third of
      bacteria presented a high resistance to UVB and almost all isolates presented an
      efficient post-irradiation recovery. Only few strains showed cell survival to
      high concentration of H(2)O(2). No correlation between the sampling sites and the
      bacterial UVB resistance was observed. Two marine bacteria, Erythrobacter flavus
      and Ruegeria mobilis, were of particular interest, presenting a good response to
      the three parameters (UVB and H(2)O(2) resistance/efficient repair).
      Unexpectedly, two resistant strains were again identified as Ruegeria species
      underlining that this geographically widespread genus, resist to UVB regardless
      the environment from which the isolates originate.

PMID- 23165169
TI  - New kinetic model for predicting the photoreactivation of bacteria with sunlight.
AB  - Exposure to ultraviolet radiation is a disinfection process that is used
      worldwide for the treatment of wastewater in order to minimize microbial
      contamination caused by wastewater discharge to natural waters. Once organisms
      have been exposed to ultraviolet radiation, they are able to repair the damage
      through two processes - dark repair and photoreactivation. In the work described
      here, the photoreactivation process after ultraviolet disinfection has been
      studied in pure culture of Escherichia coli ATCC 11229, ATCC 15597 and in real
      wastewater, using both a laboratory plant and a pilot plant. A new kinetic model
      is proposed that is a modification of the model proposed by Kashimada et al. [15]
      including a first order decay phase. This model was applied to the
      photoreactivation process with sunlight. The new model incorporates a decay rate
      constant (M(s)) for solar reactivation in order to explain correctly the decay
      phase detected in the experimental data for photoreactivation with sunlight. The
      new model fits the data obtained in reactivation experiments, thus allowing the
      interpretation of the kinetic parameters S(m), S(m)-S(o), k(s), and M(s) and
      their relationship with UV dose.

PMID- 23165170
TI  - Oxidative degradation of acid orange 7 using Ag-doped zinc oxide thin films.
AB  - Ag-doped ZnO thin films with preferred c-axis orientation along (002) have been
      prepared by spray pyrolysis technique in aqueous medium on to the corning glass
      substrates. The effect of Ag-doping on to the photoelectrochemical, structural,
      morphological, optical, luminescence, electrical and thermal properties has been
      investigated. XRD and Raman study indicates that the films have hexagonal
      (wurtzite) crystal structure. The effect of Ag loading on the photocatalytic
      activity of Ag-doped ZnO in the degradation of azo dye is studied and results are
      compared with pure ZnO. The results show that the rate of degradation of azo dye
      over Ag-doped ZnO is much higher as compared to pure ZnO. Ag doping in ZnO is
      highly effective and can significantly enhance the photocatalytic degradation and
      mineralization of azo dye. The enhancement of photocatalytic activity of Ag-doped
      ZnO thin films is mainly due to their smaller crystallite size and capability for
      reducing the electron-hole pair recombination. Kinetic parameters have been
      investigated in terms of a first order rate equation. The rate constant (-k) for
      this heterogeneous photocatalysis is evaluated as a function of the initial
      concentration of original species. Substantial reduction in azo dye is achieved
      as analyzed from COD and TOC studies.

PMID- 23165171
TI  - Light scattering on the structural characterization of DMPG vesicles along the
      bilayer anomalous phase transition.
AB  - Highly charged vesicles of the saturated anionic lipid dimyristoyl
      phosphatidylglycerol (DMPG) in low ionic strength medium exhibit a very peculiar
      thermo-structural behavior. Along a wide gel-fluid transition region, DMPG
      dispersions display several anomalous characteristics, like low turbidity, high
      electrical conductivity and viscosity. Here, static and dynamic light scattering
      (SLS and DLS) were used to characterize DMPG vesicles at different temperatures.
      Similar experiments were performed with the largely studied zwitterionic lipid
      dimyristoyl phosphatidylcholine (DMPC). SLS and DLS data yielded similar
      dimensions for DMPC vesicles at all studied temperatures. However, for DMPG,
      along the gel-fluid transition region, SLS indicated a threefold increase in the
      vesicle radius of gyration, whereas the hydrodynamic radius, as obtained from
      DLS, increased 30% only. Despite the anomalous increase in the radius of
      gyration, DMPG lipid vesicles maintain isotropy, since no light depolarization
      was detected. Hence, SLS data are interpreted regarding the presence of isotropic
      vesicles within the DMPG anomalous transition, but highly perforated vesicles,
      with large holes. DLS/SLS discrepancy along the DMPG transition region is
      discussed in terms of the interpretation of the Einstein-Stokes relation for
      porous vesicles. Therefore, SLS data are shown to be much more appropriate for
      measuring porous vesicle dimensions than the vesicle diffusion coefficient. The
      underlying nanoscopic process which leads to the opening of pores in charged DMPG
      bilayer is very intriguing and deserves further investigation. One could envisage
      biotechnological applications, with vesicles being produced to enlarge and
      perforate in a chosen temperature and/or pH value.

PMID- 23165172
TI  - Comparative assessment of therapeutic response to physiotherapy with or without
      botulinum toxin injection using diffusion tensor tractography and clinical scores
      in term diplegic cerebral palsy children.
AB  - The present study was to compare the effects of combined therapy [botulinum (BTX)
      plus physiotherapy] with physiotherapy alone using diffusion tensor imaging (DTI)
      derived fractional anisotropy (FA) values of motor and sensory fiber bundles and
      clinical grade of the disability to see the value of BTX in term children with
      spastic diplegic cerebral palsy (CP). Clinically diagnosed 36 children
      participated in the study. All these children were born at term, and had no
      history of seizures. The study was randomly categorized into two groups: group I
      (n=18) - physiotherapy alone and group II (n=18) - physiotherapy plus BTX
      injection. Quantitative diffusion tensor tractography on all these children was
      performed on motor and sensory fiber bundles on baseline as well as after 6months
      of therapy. Motor function and clinical grades were also measured by gross motor
      function measures (GMFM) scale on both occasions. We observed significant change
      in FA value in motor and sensory fiber bundle as well as in GMFM scores at
      6months compared to baseline study in both the groups. However, delta change and
      relative delta change in FA values of sensory and motor fiber bundle as well as
      GMFM score between group I and group II was statistically insignificant. We
      conclude that addition of BTX to physiotherapy regimen does not influence the
      outcome at 6months with similar insult in children with term diplegic spastic CP.
      This information may influence management of diplegic CP especially in developing
      countries, where BTX is beyond the reach of these children. 

PMID- 23165173
TI  - The endoscopic endonasal approach for recurrent pituitary lesions.

PMID- 23165174
TI  - Refocusing continuing medical education in neurosurgery.

PMID- 23165175
TI  - The pediatrics milestones: initial evidence for their use as learning road maps
      for residents.
AB  - OBJECTIVE: As the next step in competency-based medical education, the Pediatrics
      Milestone Project seeks to provide a learner-centered approach to training and
      assessment. To help accomplish this goal, this study sought to determine how
      pediatric residents understand, interpret, and respond to the Pediatrics
      Milestones. METHODS: Cognitive interviews with 48 pediatric residents from all
      training levels at 2 training programs were conducted. Each participant reviewed
      one Pediatrics Milestone document (PMD). Eight total Pediatrics Milestones,
      chosen for their range of complexity, length, competency domain, and primary
      author, were included in this study. Six residents, 2 from each year of residency
      training, reviewed each PMD. Interviews were transcribed and coded using
      inductive methods, and codes were grouped into themes that emerged. RESULTS: Four
      major themes emerged through coding and analysis: 1) the participants' degree of
      understanding of the PMDs is sufficient, often deep; 2) the etiology of
      participants' understanding is rooted in their experiences; 3) there are
      qualities of the PMD that may contribute to or detract from understanding; and 4)
      participants apply their understanding by noting the PMD describes a
      developmental progression that can provide a road map for learning. Additionally,
      we learned that residents are generally comfortable being placed in the middle of
      a series of developmental milestones. Two minor themes focusing on interest and
      practicality were also identified. CONCLUSIONS: This study provides initial
      evidence for the Pediatrics Milestones as learner-centered documents that can be
      used for orientation, education, formative feedback, and, ultimately, assessment.

PMID- 23165176
TI  - Trends in medical error education: are we failing our residents?
AB  - BACKGROUND: The Institute of Medicine has called for physician education as a key
      step in medical error prevention. In our 2002 national survey, pediatric resident
      education about medical error prevention was sporadic. We sought to describe the
      amount and type of pediatric resident training about medical errors and to assess
      the change in training since 2002. METHODS: We surveyed a national sample of 50
      pediatric chief residents randomly selected from the 198 Accreditation Council
      for Graduate Medical Education-accredited residency programs from August to
      November 2010. The 31-item telephone survey was developed from the 2002 survey,
      with the addition of 10 items about electronic learning and resident quality
      improvement projects. The survey included 4 domains: current patient safety
      curriculum, chief resident knowledge, learning from medical errors, and
      demographics. RESULTS: We phoned 55 chief residents and contacted 51. Fifty
      participated (90% participation rate). Ninety-four percent of chief residents
      stated that their program had a formalized curriculum to discuss medical errors,
      compared to only 50% (P < .001) in 2002. Ninety-six percent understood that the
      response to a medical error should be systemic change. The primary method for
      educating residents about medical error reported was informal teaching. Ninety
      two percent reported never or rarely discussing medical error in an outpatient
      setting. Seventy-four percent of chief residents reported that they never or
      rarely learn from an error made by an attending physician, and 50% never or
      rarely learned from an error made by a fellow resident. CONCLUSIONS: Although
      resident education about medical errors has improved since 2002, opportunities to
      model learning from mistakes are frequently missed.

PMID- 23165177
TI  - New perspectives on the surgical anatomy and nomenclature of the temporal region:
      literature review and dissection study.
AB  - BACKGROUND: Understanding of the temporal region remains confused, largely
      because of the ambiguous nomenclature. Aspects of the anatomy also remain unclear
      and are variably reported in the literature. The aim of this study was twofold:
      (1) to clarify details of the anatomy, using fresh cadaver dissections; and (2)
      to propose a standardized nomenclature that is based on recognized principles of
      nomenclature, contemporary use, and correct anatomical detail. METHODS: A cadaver
      dissection study on 24 fresh hemifaces (13 male, 11 female; mean age, 72 years)
      was undertaken at the University of Melbourne to clarify the anatomy of the
      tissue layers and dissection planes of the region. A comprehensive literature
      review was undertaken to clarify the nomenclature of the region and to
      investigate the current understanding of the anatomy itself. RESULTS: The tissue
      layers, ligamentous structures, and anatomy of two separate soft-tissue
      compartments within the temporal region were consistently identified across all
      dissection specimens. A standardized nomenclature system for the temporal region
      has been proposed. CONCLUSIONS: The use of consistent nomenclature to describe
      the structures in the temporal region facilitates understanding and discussion of
      the anatomy. Two separate soft-tissue compartments exist in the temporal region,
      bounded by ligamentous structures. The tissue layers differ considerably between
      the two compartments, and anatomical landmarks within these layers provide useful
      information to the surgeon operating in the temporal region.

PMID- 23165179
TI  - Online home self-assessment: a tool for improving future treatment trials?

PMID- 23165180
TI  - Reply to the comment by Verhoeven et al. about the article "Efficacy of anakinra
      in articular chondrocalcinosis--report of three cases" Joint Bone Spine
      2012;79:330-1.

PMID- 23165181
TI  - BAFF levels in patients with ankylosing spondylitis and response to anti-tumor
      necrosis factor treatment.

PMID- 23165178
TI  - Insect microRNAs: biogenesis, expression profiling and biological functions.
AB  - MicroRNAs (miRNA) are a class of endogenous regulatory RNA molecules 21-24
      nucleotides in length that modulate gene expression at the post-transcriptional
      level via base pairing to target sites within messenger RNAs (mRNA). Typically,
      the miRNA "seed sequence" (nucleotides 2-8 at the 5' end) binds complementary
      seed match sites within the 3' untranslated region of mRNAs, resulting in either
      translational inhibition or mRNA degradation. MicroRNAs were first discovered in
      Caenorhabditis elegans and were shown to be involved in the timed regulation of
      developmental events. Since their discovery in the 1990s, thousands of potential
      miRNAs have since been identified in various organisms through small RNA cloning
      methods and/or computational prediction, and have been shown to play functionally
      important roles of gene regulation in invertebrates, vertebrates, plants, fungi
      and viruses. Numerous functions of miRNAs identified in Drosophila melanogaster
      have demonstrated a great significance of these regulatory molecules. However,
      elucidation of miRNA roles in non-drosophilid insects presents a challenging and
      important task.

PMID- 23165182
TI  - Update on gout 2012.
AB  - Significant scientific advances have been made over the last five years in the
      pathogenesis of hyperuricemia and understanding how monosodium urate (MSU)
      crystals provoke gout. New detection methods using ultrasound (US) have been
      evaluated and may become part of our routine diagnostic approach in a patient
      presenting with gout. This review will concentrate on the latest developments in
      the field, and discuss how these data may impact on clinical practice. Finally, a
      brief review of the therapeutic implications and new therapies that have become
      available will be presented.

PMID- 23165183
TI  - Systematic review of manual therapies for nonspecific neck pain.
AB  - OBJECTIVE: To evaluate the effectiveness of manual therapies in the treatment of
      nonspecific neck pain. MATERIALS AND METHODS: Medline and the Cochrane Library
      were searched for randomized controlled trials of manual therapy or mobilization,
      used alone or with exercises to treat pain and functional impairment related to
      nonspecific neck pain. Cochrane Back Review Group criteria were used to assess
      the quality of the trials and the level of evidence (unclear, limited, moderate,
      or high) for short-, medium-, and long-term effects. RESULTS: Of 27 identified
      trials, 18 were of high quality. In acute neck pain, effective treatments were
      thoracic manipulation combined with electrothermal therapy in the short term and
      cervical manipulation in the long term. In chronic neck pain and neck pain of
      variable duration, both pain and function improved consistently at all follow-up
      time points. None of the manual therapies used alone or in combination was
      superior over the others. In the long term, exercises alone or combined with
      manual therapies were superior over manual therapies used alone. CONCLUSION:
      Manual therapies contribute usefully to the management of nonspecific neck pain.
      The level of evidence is moderate for short-term effects of upper thoracic
      manipulation in acute neck pain, limited for long-term effects of neck
      manipulation, and limited for all techniques and follow-up durations in chronic
      neck pain.

PMID- 23165185
TI  - The nature of confounding in genome-wide association studies.
AB  - The authors argue that population structure per se is not a problem in genome
      wide association studies - the true sources are the environment and the genetic
      background, and the latter is greatly underappreciated. They conclude that mixed
      models effectively address this issue.

PMID- 23165186
TI  - Small RNA: RNAi doesn't overdo it.

PMID- 23165187
TI  - Applying quantitative structure-activity relationship approaches to
      nanotoxicology: current status and future potential.
AB  - The potential (eco)toxicological hazard posed by engineered nanoparticles is a
      major scientific and societal concern since several industrial sectors (e.g.
      electronics, biomedicine, and cosmetics) are exploiting the innovative properties
      of nanostructures resulting in their large-scale production. Many consumer
      products contain nanomaterials and, given their complex life-cycle, it is
      essential to anticipate their (eco)toxicological properties in a fast and
      inexpensive way in order to mitigate adverse effects on human health and the
      environment. In this context, the application of the structure-toxicity paradigm
      to nanomaterials represents a promising approach. Indeed, according to this
      paradigm, it is possible to predict toxicological effects induced by chemicals on
      the basis of their structural similarity with chemicals for which toxicological
      endpoints have been previously measured. These structure-toxicity relationships
      can be quantitative or qualitative in nature and they can predict toxicological
      effects directly from the physicochemical properties of the entities (e.g.
      nanoparticles) of interest. Therefore, this approach can aid in prioritizing
      resources in toxicological investigations while reducing the ethical and monetary
      costs that are related to animal testing. The purpose of this review is to
      provide a summary of recent key advances in the field of QSAR modelling of
      nanomaterial toxicity, to identify the major gaps in research required to
      accelerate the use of quantitative structure-activity relationship (QSAR)
      methods, and to provide a roadmap for future research needed to achieve QSAR
      models useful for regulatory purposes. 

PMID- 23165188
TI  - Prognostic factors in gastrointestinal stromal tumors: multicenter experience of
      333 cases from Turkey.
AB  - BACKGROUND/AIMS: Gastrointestinal stromal tumors (GISTs) are the most common
      mesenchymal neoplasm of the gastrointestinal tract. In an attempt to survey the
      approximate incidence, clinicopathological characteristics, and immunophenotypic
      features of GISTs in Turkey, we conducted a clinicopathological and
      immunohistochemical analysis of GISTs. METHODOLOGY: Three hundred and thirty
      three patients with GIST from nine institutions in Turkey were retrospectively
      evaluated. RESULTS: Between January 2001 and March 2011, a total of 333 patients
      with GISTs were included; of these, 204 (61.2%) were male and 129 (38.8%) were
      female. The median age was 55 years (range; 22-102 years). At the median follow
      up of 26 months (range; 4-166 months), the 1-, 3- and 5-year OS rates of the 333
      patients were 96.9%, 85.8% and 78.5%, respectively. The 5-year DFS rate was 40%.
      The 5-year OS rate and median OS time for the patients with R0 resection were
      significantly higher than for patients with metastatic diseases (79.7 vs. 75.7%
      and not reached vs. 115 months, respectively, p=0.04). CONCLUSION: Although our
      results should be confirmed by prospective studies, we believe that they
      contribute to the literature because the study included both resectable and
      metastatic or unresectable GIST patients and multicenter findings from Turkey.

PMID- 23165189
TI  - Efficacy of sunitinib in Turkish patients with gastrointestinal stromal tumors;
      retrospective multicenter experience.
AB  - BACKGROUND/AIMS: Sunitinib is a multi-targeted thyrosine kinase receptor
      inhibitor used in patients with advanced gastrointestinal stromal tumours
      (GISTs). We evaluated the efficacy and tolerability of sunitinib therapy in
      Turkish patients with GISTs. METHODOLOGY: Between January 2001 and April 2012, 57
      patients who had progressive disease or experienced unacceptable toxicity during
      imatinib treatment from multiple centers were investigated retrospectively.
      RESULTS: Thirty-three patients were male and 24 were female. The median age was
      55 years (range; 16-84 years). Thirty-eight of the patients received imatinib for
      longer than 12 months, 13 patients received for 6-12 months, and 6 patients
      received for less than six months. The clinical benefit of sunitinib was 73.7%.
      Treatment-related adverse events were reported in 78% of the patients. Adverse
      events were generally mild to moderate in intensity. The median progression free
      survival (PFS) and overall survival (OS) of the patients that received sunitinib
      were 10.8 months and 23.9 months, respectively. The time of imatinib usage and
      response to sunitinib were independent prognostic factors for PFS and OS. Also,
      tumor size was an independent prognostic factor for PFS. CONCLUSIONS: Sunitinib
      is an effective treatment in Turkish patients with GISTs, with a clinical benefit
      of 73.7% and shows an acceptable tolerability.

PMID- 23165190
TI  - eEF1A2 protein expression correlates with lymph node metastasis and decreased
      survival in pancreatic ductal adenocarcinoma.
AB  - BACKGROUND/AIMS: To examine eukaryotic elongation factor1A2 (eEF1A2) expression
      in pancreatic ductal adenocarcinoma (PDA) and to analyze its relationship with
      the clinicopathol!ogy of PDA. METHODOLOGY: eEF1A2 expression was examined in 97
      PDA specimens by immunohistochemistry. We also analyzed the association between
      FAP expression in PDAC cells and the clinicopathology of PDA patients. RESULTS:
      eEF1A2 expression was absent in normal pancreatic tissue. In contrast, in PDA,
      eEF1A2 showed positive immunoreactivity in 76 of 97 (77.8%) PDA cases. We found
      significant associations between increased eEF1A2 expression and the presence of
      nodal metastasis (p=0.039) and perineural invasion (p=0.043). Univariate analysis
      of survival showed that the median overall survival time of eEF1A2-positive PDA
      patients (11.7 months) was significantly shorter than that of eEF1A2-negative
      PDAC patients (17.5 months; p<0.001). In addition, when the Cox proportion hazard
      model was used in multivariate survival analysis, we revealed that eEF1A2
      expression (p<0.001; hazard rate, 95%CI 2.91-13.61) and TNM stage (p<0.001 hazard
      rate, 95%CI 0.18-0.23) still remained statistically significant. CONCLUSIONS:
      eEF1A2 is highly expressed in PDA, and its expression is associated with nodal
      metastasis and perineural invasion, as well as worse prognosis.

PMID- 23165191
TI  - A comparison of the clinical features and prognosis of pancreatic head cancer
      with that of other periampullary cancers.
AB  - BACKGROUND/AIMS: Our purpose was to compare the clinical features and prognosis
      of pancreatic head cancer with that of other periampullary cancers. METHODOLOGY:
      The medical records of 82 patients (mean age of 61.67+/-10.52 years) with ductal
      adenocarcinoma of the head of pancreas and 73 patients (mean age of 60.52+/-11.72
      years) with other periampullary adenocarcinomas, all of whom had received radical
      surgery, were retrospectively analyzed. RESULTS: There were no significant
      differences in age and gender between the groups (both, p>0.05). However, there
      were significant differences in lymph node metastasis, TNM stage, clear surgical
      margins, tumor size, and neural invasion between the 2 groups (all p<0.05).
      Patients with pancreatic head adenocarcinoma had significantly higher red blood
      cell (RBC) count and hemoglobin (Hb), albumin and pre-albumin levels, and higher
      platelet and white blood cell (WBC) counts than the patients with other
      periampullary adenocarcinomas (all p<0.05). No differences in carcinoembryonic
      antigen (CEA) or CA19-9 were noted between the groups. The 1-year survival rates
      were not different between the groups (p=0.299). CONCLUSIONS: Pancreatic head
      carcinoma has different clinical manifestations and biological features than
      other periampullary cancers.

PMID- 23165192
TI  - CCR7: A metastasis and prognosis indicator of postoperative patients with
      esophageal carcinoma.
AB  - BACKGROUND/AIMS: To investigate the expression of CC chemokine receptor 7 (CCR7)
      and its relationship to the metastasis and prognosis in esophageal squamous cell
      carcinoma (ESCC) after esophagectomy. METHODOLOGY: CCR7 expression was detected
      by immunohistochemistry. Kaplan-Meier method was performed to calculate the
      survival rate, Cox regression multivariate analysis was performed to determine
      independent prognostic factors. RESULTS: CCR7 expression rate in T1, T2 and T3
      patients was 27.3%, 64.7% and 75.2%, respectively, the difference of CCR7 protein
      expression was statistically significant (p=0.000). The positive expression of
      CCR7 in patients with lymph node metastasis was significantly higher than those
      without metastasis (p=0.000). CCR7 expression correlated with significantly
      worsened 5-year survival for all patients as well as those with T2 and T3 tumors,
      N0 nodal status or N1 nodal status. The result of Cox analysis demonstrated that
      N stage, T stage and CCR7 expression were independent prognostic factors.
      CONCLUSIONS: CCR7 expression was detected in ESCC and was found to be
      significantly associated with T stage and lymph node metastasis. The 5-year
      survival rate was significantly lower in patients with CCR7 expression in those
      without. Invasion, lymph node metastasis and CCR7 expression were independent
      factors.

PMID- 23165193
TI  - Perioperative immunological differentiation in liver cirrhotic patients who
      underwent living related liver transplantation.
AB  - BACKGROUND/AIMS: Liver cirrhotic patients are immunological compromised hosts.
      Preoperative status in cirrhotic patients affects postoperative infection
      complications. This study investigates the perioperative immunological changes in
      the differentiation by MELD score. METHODOLOGY: Fifteen patients underwent LDLT
      and were divided two groups, Group I (n=5, MELD score >=20) and Group II (n=10,
      MELD score <20). Immunological status of cirrhotic patients was analyzed for Th1,
      Th2, Treg and Th17 by flow cytometry using monoclonal antibody CD3/CD19,CD4/8,
      FoxP3, IL-17, IFN-gamma and TNF-alpha. RESULTS: T cell decreased and increased
      gradually following LDLT. The preoperative T cell count of MELD score 33 patients
      was very low. CD4 and CD8 T cells also decreased after LDLT. The preoperative
      CD8+ T cell count of MELD score 33 patients was very low. Th17 decreased and
      recovered gradually in the all patients after LDLT. However Th17 of MELD score 33
      did not recover. IFN-gamma-producing cells in naive T cells decreased after LDLT.
      Preoperatively those in the Group I was lower than those in the Group II. The
      population of Treg decreased in the Group I, however, it increased in the Group
      II on 7 days after LDLT. CONCLUSIONS: The patients with MELD score >20 showed a
      decrease of cytotoxic immunity with both diminution and delay of CD8+ T cells and
      Th17 helper T cells. The cytotoxic immunity of the patients with MELD score <20
      was maintained and recovered in the early period after LDLT. The patients with
      MELD score >20 might be at high risk of infection after LDLT.

PMID- 23165194
TI  - Correlations between obesity/metabolic syndrome-related factors and risk of
      developing colorectal tumors.
AB  - BACKGROUND/AIMS: Colorectal cancer/adenoma development may correlate with
      obesity/metabolic syndrome in the Japanese. We sought to clarify the relation
      between colorectal adenoma prevalence and various factors to develop a better
      colorectal tumor screening strategy. METHODOLOGY: Of 2668 patients who underwent
      colonoscopy, medical records of 837 patients (467 men, 370 women; age, 40-80
      years) with available data on measured values of body mass index, waist
      circumference, body fat percentage, and prior history of hypertension, diabetes
      and hyperlipidemia were reviewed and analyzed. RESULTS: Of these patients, 460
      (55.0%) had colorectal tumor or prior history thereof (lesions >=1mm).
      Multivariate analysis revealed significant differences in gender, age and waist
      circumference between patients with/without colorectal adenoma, with men at
      significantly higher risk than women of developing colorectal tumor (OR=2.57, 95%
      CI: 1.84-4.65; p<0.001). In patients with/without colorectal tumor, age, waist
      circumference and body fat percentage were significantly different among men, but
      only age was significantly different among women. CONCLUSIONS: Present findings
      that waist circumference and body fat percentage correlated with prevalence of
      colorectal tumor among men may contribute to more accurate prediction of
      colorectal tumor risk and an efficient colorectal cancer screening system.

PMID- 23165196
TI  - Chemically orthogonal trifunctional Janus beads by photochemical "sandwich"
      microcontact printing.
AB  - The combination of topographic and chemical orthogonality on polymer particles by
      site selective immobilization of functional thiols via thiol-ene chemistry
      provides a trifunctional particle surface with azide and acid functionalities on
      opposing poles and alkenes in the equatorial area. These Janus beads are
      accessible for site selective orthogonal chemical reactions as well as
      biomolecular recognition on the same particle.

PMID- 23165195
TI  - SAA does not induce cytokine production in physiological conditions.
AB  - SAA has been shown to have potential proinflammatory properties in inflammatory
      diseases such as atherosclerosis. These include induction of tumor necrosis
      factor alpha, interleukin-6, and monocyte chemoattractant protein 1 in vitro.
      However, concern has been raised that these effects might be due to use of
      recombinant SAA with low level of endotoxin contaminants or its non-native forms.
      Therefore, physiological relevance has not been fully elucidated. In this study,
      we investigated the role of SAA in the production of inflammatory cytokines.
      Stimulation of mouse monocyte J774 cells with lipid-poor recombinant human SAA
      and purified SAA derived from cardiac surgery patients, but not ApoA-I and ApoA
      II, elicited pro-inflammatory cytokines like granulocyte colony stimulating
      factor (G-CSF). However, HDL-associated SAA failed to stimulate production of
      these cytokines. Using neutralizing antibodies against toll like receptor (TLR) 2
      and 4, we could evaluate that TLR 2 is responsible for G-CSF production by lipid
      poor SAA. To confirm these data in vivo, we expressed mouse SAA in SAA deficient
      C57BL/6 mice using an adenoviral vector. G-CSF was identically expressed in SAA
      Adenoviral infected mice as well as in control null-Adenoviral mice at the early
      time points (4-8h) and could not be detected in plasma 24h after infection when
      plasma SAA levels were maximally elevated, indicating that adenoviral vector
      rather than SAA affected G-CSF levels. Taken together, our findings suggest that
      lipid-poor SAA, but not HDL-associated SAA, stimulates G-CSF production and this
      stimulation is mediated through TLR 2 in J774 cells. However, its physiological
      role in vivo remains ambiguous.

PMID- 23165197
TI  - How sweet it isn't: a new formulation of sodium phenylbutyrate and the challenge
      of palatability for medicines for children.

PMID- 23165198
TI  - [Development of indicators to promote measures for the prevention and
      rehabilitation of functional decline in older people].
AB  - BACKGROUND: In Europe and Asia, long-term care funding is disability-based. This
      introduces a perverse effect by inappropriately adding value to functional
      decline among beneficiaries. To support the efforts in prevention and
      rehabilitation made by personnel in long-term care services, indicators have to
      be developed to promote functional improvement of beneficiaries. As people
      receiving those services are already experiencing a functional decline process,
      it is essential to know the natural magnitude of functional decline in order to
      assess deviation from this expected decline. The objective of the study was to
      estimate the natural decrease of autonomy in beneficiaries of home care services
      and nursing homes. METHODS: Two databases were used: for home-dwelling people,
      1235 subjects over 75 years old who participated in the PRISMA study; for
      institutions, 1330 residents over 65 years old of a nursing home in Sherbrooke
      (QC, Canada). These subjects were assessed several times over many years with the
      Functional Autonomy Measurement System (SMAF). Growth analyses were used to
      estimate the annual decrease in the SMAF score according to age, gender and the
      initial autonomy status. RESULTS: At home, only age was significantly associated
      with the slope of functional decline. The average annual decrease of subjects 75
      84 years old was 2.4 points on the SMAF score (out of 87); for those aged over
      85, the annual loss was 3.8 points. In institutions, gender and the initial
      autonomy profile were associated with the annual decrease. For men, the annual
      decrease varied between 0.7 for the most disabled subjects to 5.2 for the most
      autonomous. For women, those values varied from 0.2 to 6.6, respectively.
      CONCLUSION: A decrease in the SMAF score less than these expected values should
      be associated with a bonus to support personnel training, prevention activities,
      rehabilitation and activities aimed at supporting the autonomy of the
      beneficiaries. Such a strategy requires the implementation of a precise and
      reliable assessment instrument like the SMAF and also the availability of a
      longitudinal database where data for each beneficiary could be linked over time.

PMID- 23165199
TI  - A simple Fourier transform-based reconstruction formula for photoacoustic
      computed tomography with a circular or spherical measurement geometry.
AB  - Photoacoustic computed tomography (PACT), also known as optoacoustic tomography,
      is an emerging imaging modality that has great potential for a wide range of
      biomedical imaging applications. In this note, we derive a hybrid reconstruction
      formula that is mathematically exact and operates on a data function that is
      expressed in the temporal frequency and spatial domains. This formula explicitly
      reveals new insights into how the spatial frequency components of the sought
      after object function are determined by the temporal frequency components of the
      data function measured with a circular or spherical measurement geometry in two-
      and three-dimensional implementations of PACT, respectively. The structure of the
      reconstruction formula is surprisingly simple compared with existing Fourier
      domain reconstruction formulae. It also yields a straightforward numerical
      implementation that is robust and two orders of magnitude more computationally
      efficient than filtered backprojection algorithms.

PMID- 23165200
TI  - The effect of working memory capacity on conflict monitoring.
AB  - The conflict adaptation effect, a reduced interference effect upon the detection
      of a conflict signal (e.g., following an incongruent trial), has been interpreted
      as evidence for active regulation of top-down cognitive control. We hypothesized
      that the extent of conflict adaptation should be related to individuals' working
      memory capacity (WMC), which has been repeatedly demonstrated to reflect the
      level of cognitive control. Using the Simon task, in Experiment 1, we quantified
      the conflict adaptation ratio (CAR) transiently as the ratio of the conflict
      effect following an incongruent trial to the conflict effect following a
      congruent trial, controlling for the reaction time that often correlates with
      WMC. We observed that the CAR varied from highly negative with low WMC scores to
      near-zero with high WMC scores. This result suggests that high WMC individuals,
      when detecting conflict, adjust the level of cognitive control optimally so that
      their performance is less susceptible to the presence of a distractor. In
      Experiment 2, we quantified the CAR in a sustained manner as the ratio of the
      conflict effect from predominantly incongruent blocks to the conflict effect from
      predominantly congruent blocks. Again, the CAR varied from negative to zero as
      WMC increased. These results suggest that WMC may reflect, in addition to the
      ability to maintain a level of control, the ability to adjust the level of
      control appropriately to the contextual demands.

PMID- 23165201
TI  - Can readers ignore implausibility? Evidence for nonstrategic monitoring of event
      based plausibility in language comprehension.
AB  - We present evidence for a nonstrategic monitoring of event-based plausibility
      during language comprehension by showing that readers cannot ignore the
      implausibility of information even if it is detrimental to the task at hand. In
      two experiments using a Stroop-like paradigm, participants were required to
      provide positive and negative responses independent of plausibility in an
      orthographical task (Experiment 1) or a nonlinguistic color judgment task
      (Experiment 2) to target words that were either plausible or implausible in their
      context. We expected a nonstrategic assessment of plausibility to interfere with
      positive responses to implausible words. ANOVAs and linear mixed models analyses
      of the response latencies revealed a significant interaction of plausibility and
      required response that supported this prediction in both experiments, despite the
      use of two very different tasks. Moreover, it could be shown that the effect was
      not driven by the differential predictability of plausible and implausible words.
      These results suggest that plausibility monitoring is an inherent component of
      information processing.

PMID- 23165202
TI  - Far-IR excitations in Cd2Re2O7 in the normal and superconducting states.
AB  - Cd(2)Re(2)O(7) is a pyrochlore superconductor with a transition temperature T(c)
      near 1 K. We report on the far-infrared optical properties of Cd(2)Re(2)O(7) at
      temperatures above and below T(c) with a particular emphasis on changes in the
      spectrum below T(c). Seventeen phonon modes are observed in the normal state
      optical conductivity spectrum of Cd(2)Re(2)O(7) at low temperatures in good
      agreement with a factor group analysis. In the superconducting state, a softening
      (~1 cm(-1)) of the phonon modes at 35 and 61 cm(-1) occurs and thermal
      reflectance spectra show the development of two additional strong absorption
      features, near 9.6 and 19.3 cm(-1). The dominant presence of lattice vibrational
      modes in the optical spectrum suggests that electron-phonon interaction plays an
      important role in the normal and superconducting state properties of
      Cd(2)Re(2)O(7).

PMID- 23165203
TI  - Transdifferentiation by defined factors as a powerful research tool to address
      basic biological questions.

PMID- 23165204
TI  - Oncogenic pathway utilizes mitochondrial fusion machinery to support growth.

PMID- 23165205
TI  - Control of seed germination in the shade.

PMID- 23165206
TI  - Telomere-binding proteins play roles in control of replication timing.
AB  - Comment on: Tazumi A, et al. Genes Dev 2012; 26:2050-62.

PMID- 23165207
TI  - Uncovering the interplay between DNA sequence preferences of transcription
      factors and nucleosomes.

PMID- 23165209
TI  - A coordinated codon-dependent regulation of translation by Elongator.
AB  - More than a decade ago, the purification of the form of the RNA polymerase II
      (PolII) engaged in elongation led to the discovery of an associated, multi
      subunit (Elp1-6) complex named "Elongator" by the Svejstrup lab. Although further
      evidence supported the original notion that Elongator is involved in
      transcription, Elongator lacked some of the expected features for a regulator of
      the elongating PolII. The discovery by the Bystrom lab, based on genetic
      dissection, that Elongator is pivotal for tRNA modifications, and that all the
      reported phenotypes of Elongator mutants are suppressed by the overexpression of
      two tRNAs added to the confusion. The increasing range of both potential
      substrates and biological processes regulated by Elongator in higher eukaryotes
      indicates that the major challenge of the field is to determine the biologically
      relevant function of Elongator. Our recent proteome-wide study in fission yeast
      supports a coordinated codon-dependent regulation of translation by Elongator.
      Here we provide additional analyses extending this hypothesis to budding yeast
      and worm.

PMID- 23165208
TI  - A role for polyamine regulators in ESC self-renewal.
AB  - Embryonic stem cells (ESCs) depend on extensive regulatory networks to coordinate
      their self-renewal and differentiation. The polyamine pathway regulator AMD1 was
      recently implicated in ESC self-renewal and directed differentiation of ESCs to
      neural precursor cells (NPCs). The polyamines spermine and spermidine are
      essential for a wide range of biological processes, and their levels are tightly
      regulated. Here, we review the polyamine pathway and discuss how it can impact
      polyamine levels, cellular methylation and hypusinated EIF5A levels. We discuss
      how it could feed into regulation of ESC self-renewal and directed
      differentiation. We show that in addition to AMD1, a second rate-limiting enzyme
      in the polyamine pathway, ODC1, can also promote ESC self-renewal, and that both
      Amd1 and Odc1 can partially substitute for Myc during cellular reprogramming. We
      propose that both Amd1 and Odc1 are essential regulators of ESCs and function to
      ensure high polyamine levels to promote ESC self-renewal.

PMID- 23165210
TI  - p53 contributes to T cell homeostasis through the induction of pro-apoptotic SAP.
AB  - Lack of functional SAP protein, due to gene deletion or mutation, is the cause of
      X-linked lymphoproliferative disease (XLP), characterized by functionally
      impaired T and NK cells and a high risk of lymphoma development. We have
      demonstrated earlier that SAP has a pro-apoptotic function in T and B cells.
      Deficiency of this function might contribute to the pathogenesis of XLP. We have
      also shown that SAP is a target of p53 in B cell lines. In the present study, we
      show that activated primary T cells express p53, which induces SAP expression.
      p53 is functional as a transcription factor in activated T cells and induces the
      expression of p21, PUMA and MDM2. PARP cleavage in the late phase of activation
      indicates that T cells expressing high levels of SAP undergo apoptosis. Modifying
      p53 levels using Nutlin-3, which specifically dissociates the MDM2-p53
      interaction, was sufficient to upregulate SAP expression, indicating that SAP is
      a target of p53 in T cells. We also demonstrated p53's role as a transcription
      factor for SAP in activated T cells by ChIP assays. Our result suggests that p53
      contributes to T cell homeostasis through the induction of the pro-apoptotic SAP.
      A high level of SAP is necessary for the activation-induced cell death that is
      pivotal in termination of the T cell response.

PMID- 23165211
TI  - Pro- and anti-apoptotic effects of p53 in cisplatin-treated human testicular
      cancer are cell context-dependent.
AB  - In murine testicular cancer (TC) cells wild-type p53 contributes to sensitivity
      to DNA-damaging drugs in a dose-dependent way. In human TC, however, the role of
      wild-type p53 functionality in chemotherapeutic response remains elusive. We
      analyzed functionality of wild-type p53 in cisplatin sensitivity in the human TC
      setting using a p53 short interfering (si)RNA approach. The cisplatin-sensitive
      TC cell line (Tera), the subline with acquired cisplatin resistance (Tera-CP) and
      a panel of intrinsically resistant TC cell lines (Scha and 2102EP), all
      expressing wild-type p53, were used. p53 and p53 transcriptional targets MDM2 and
      p21 (Waf1/Cip1)  (p21) were expressed in a p53 transactivation-dependent way in
      all TC cell lines. Following cisplatin exposure, expression levels of p53
      increased, with a subsequent increase in MDM2 and p21 mRNA and protein levels and
      Fas cell membrane levels. Downregulation of p53 with siRNA lowered cisplatin
      induced apoptosis in Tera and Tera-CP, which was associated with a diminished Fas
      membrane expression. In contrast, p53 suppression augmented cisplatin-induced
      apoptosis in Scha and 2102EP and concomitantly strongly suppressed MDM2 and p21
      mRNA and protein expression. Our results indicate that p53 is involved in
      transactivation of pro- and anti-apoptotic genes in untreated and cisplatin
      treated TC cells, but subtle differences are present between TC cell lines. The
      opposite role of p53 in cisplatin-induced apoptosis among TC cell lines
      demonstrates the importance of the cellular context for the p53 transactivation
      phenotype in TC cells.

PMID- 23165212
TI  - Transcriptional regulation of thymine DNA glycosylase (TDG) by the tumor
      suppressor protein p53.
AB  - Thymine DNA glycosylase (TDG) belongs to the superfamily of uracil DNA
      glycosylases (UDG) and is the first enzyme in the base-excision repair pathway
      (BER) that removes thymine from G:T mismatches at CpG sites. This glycosylase
      activity has also been found to be critical for active demethylation of genes
      involved in embryonic development. Here we show that wild-type p53
      transcriptionally regulates TDG expression. Chromatin immunoprecipitation (ChIP)
      and luciferase assays indicate that wild-type p53 binds to a domain of TDG
      promoter containing two p53 consensus response elements (p53RE) and activates its
      transcription. Next, we have used a panel of cell lines with different p53 status
      to demonstrate that TDG mRNA and protein expression levels are induced in a p53
      dependent manner under different conditions. This panel includes isogenic breast
      and colorectal cancer cell lines with wild-type or inactive p53, esophageal
      squamous cell carcinoma cell lines lacking p53 or expressing a temperature
      sensitive p53 mutant and normal human bronchial epithelial cells. Induction of
      TDG mRNA expression is accompanied by accumulation of TDG protein in both nucleus
      and cytoplasm, with nuclear re-localization occurring upon DNA damage in p53
      competent, but not -incompetent, cells. These observations suggest a role for p53
      activity in TDG nuclear translocation. Overall, our results show that TDG
      expression is directly regulated by p53, suggesting that loss of p53 function may
      affect processes mediated by TDG, thus negatively impacting on genetic and
      epigenetic stability.

PMID- 23165213
TI  - Effects of mycophenolic acid on highly sensitized patients awaiting kidney
      transplant.
AB  - BACKGROUND: 10-30% of dialysis population awaiting renal transplantation is
      sensitized. Mycophenolic acid (MPA) has been shown to reduce panel reactive
      antibody (PRA) formation in kidney transplant recipients. Our aim was to
      investigate whether MPA could effectively reduce anti-HLA antibody levels and
      allow successful transplantation. METHODS: A total of 40 highly sensitized
      patients were treated orally with MPA. All patients had T-cell PRA values greater
      than 30% (73% of patients were >= 75%). The PRAs, T-cell/B-cell flow cytometry
      crossmatch (FCXM) mean channel shift (MCS), patient/graft survival, acute
      rejection, and serum creatinine (SCr) were recorded. RESULTS: All 40 patients
      showed a decrease in PRA levels. Eighteen of the 40 patients (40%) received a
      transplant. All four living donor recipients converted to a negative crossmatch.
      There was a significant decrease in FCXM MCS in all 18 transplanted patients. The
      mean SCr at 24 months was 1.00 +/- 0.25mg/dL. Five patients (28%) experienced
      acute rejection. The overall one year actuarial patient and graft survival were
      94% and 88%, respectively. CONCLUSIONS: These findings suggest that MPA therapy
      is effective in reducing PRAs and increases the likelihood of successful
      transplantation in sensitized recipients in a potentially simpler and more cost
      effective manner than the current regimens employed.

PMID- 23165214
TI  - Sirolimus-based regimen promotes inhibitory costimulatory signal of
      HVEM/BTLA/CD160/LIGHT pathway in allo-renal recipients.
AB  - HVEM/BTLA/CD160/LIGHT pathway is a very special costimulatory molecule system
      which can regulate T-cell immune responses by activating both inflammatory and
      inhibitory signalings. The regulatory effect of Sirolimus on HVME costimulatory
      system in allo-renal recipients has not been reported. In this study, we analyzed
      the expression of HVEM, BTLA, CD160 and LIGHT on circulating T cell subgroups and
      the expression of HVEM on CD4+ Tregs by flow cytometry and also the pre-dose
      concentration of Sirolimus by automatic analyzer. Both the allo-renal recipients
      receiving Sirolimus immunosuppressive regimen and health volunteers were
      included. The expression of both BTLA and CD160 on T cells increased
      significantly while the expression of LIGHT on T cells decreased significantly in
      allo-renal recipients receiving Sirolimus regimen (p<0.05). The expression of
      HVEM on T cells and CD4+ T-cell subgroup decreased (p<0.05) while that on CD8+ T
      cell subgroup remained roughly normal (p>0.05).The expression of HVEM on CD4+
      Tregs increased significantly (p<0.05) in allo-renal recipients receiving
      Sirolimus regimen (p<0.05). Though regulating the expression of
      HVEM/BTLA/CD160/LIGHT costimulatory system, Sirolimus-based regimen promotes
      inhibitory costimulatory signal in T cells and enhances the function of CD4+
      Tregs in allo-renal recipients, which are in benefit of the control of transplant
      rejection as well as the induction and maintenance of transplant tolerance.

PMID- 23165215
TI  - Local structure and dynamics of benzene confined in the IRMOF-1 nanocavity as
      studied by molecular dynamics simulation.
AB  - The local structure and dynamic behaviour of a benzene molecular assembly
      confined within the nano-cavities of a zinc-based metal-organic framework,
      [Zn(4)O(CO(2)C(6)H(4)CO(2))(3)](n) (IRMOF-1), were investigated by means of
      molecular dynamics (MD) simulations. The local structure of the confined benzene
      molecules was evaluated using radial distribution functions. The sites for
      adsorption of benzene in IRMOF-1 were well defined by the simulation. The
      diffusion coefficients at ambient temperature suggested that the mobility of the
      confined benzene was high, comparable to the bulk fluid. Decreasing the
      temperature gave rise to the aggregation of benzene in the IRMOF-1 frameworks.
      Molecular aggregation was attributed to the localization of benzene in the large
      and the small cavities of IRMOF-1, respectively. Both the translational diffusion
      coefficient and the trajectory of benzene provided evidence that the localization
      of benzene in the large and the small cavities takes place at ca. 200 K.
      Furthermore, at high benzene loading, the migration of benzene in the small
      cavities was prevented (frozen) below 135 K. Thus, the translational degree of
      freedom of the benzene molecules changed drastically, depending on the
      temperature.

PMID- 23165216
TI  - Transoral approach for percutaneous vertebroplasty in the treatment of osteolytic
      tumor lesions of the lateral mass of the atlas: feasibility and initial
      experience in 2 patients.
AB  - STUDY DESIGN: Case series. OBJECTIVE: To report our early experience of
      percutaneous vertebro-plasty via a transoral approach of the lesions of the
      lateral mass of C1. SUMMARY OF BACKGROUND DATA: Percutaneous vertebroplasty has
      gained acceptance for the treatment of osteolytic lesions of the spine. However,
      scant data are available on the percutaneous vertebroplasty of the C1 lesions.
      METHODS: Two patients (a 74-yr-old female and a 53-yr-old male) presenting
      respectively a metastasis of the left lateral mass of C1 from a pancreatic
      adenocarcinoma and a hemangioma of the left lateral mass of C1 underwent a
      percutaneous vertebroplasty via a transoral approach in a hybrid angio suite
      associating a monoplane flat panel and a computed tomography scan, using
      polymethylmetacrilate bone cement.For the second patient, a nondetachable balloon
      was used to protect the vertebral artery from cement leakage. RESULTS:
      Satisfactory filing of the lesions was obtained in both patients. No complication
      was recorded. Both patients experienced pain improvement. CONCLUSION: Transoral
      approach for the treatment of osteolytic tumor lesions of the lateral mass of the
      atlas is feasible and seems to be a safe and effective technique.

PMID- 23165217
TI  - Detection and monitoring of ovarian cancer.
AB  - Ovarian cancer is the fifth leading cause of death among women in the United
      States and remains the most common cause of death from a gynecologic malignancy.
      Most ovarian cancers are diagnosed at an advanced stage in which 5-year survival
      rate is approximately 30%. Given that the 5-year survival rate is greater than
      90% for women diagnosed at an early stage, early detection in women presenting
      with vague symptoms is crucial to improve outcome. Diagnosis of ovarian cancer is
      largely based on symptoms, imaging, and laboratory biomarkers. Overall, more than
      200 potential biomarkers differentially expressed in ovarian cancer have been
      identified (Lokshin, 2012). However, no single marker has been found useful for
      the diagnosis of ovarian cancer. Increased sensitivity and specificity for the
      diagnosis of ovarian cancer are observed when multiple markers are used in
      combination. The Food and Drug Administration (FDA) recently cleared two
      algorithms to evaluate the risk of ovarian cancer for women who present with
      pelvic mass. In this review, we will summarize the most recent serum biomarkers
      and clinical applications of biomarkers for the early detection and treatment
      monitoring of ovarian cancers. We will also discuss the algorithms for predicting
      the risk of ovarian cancers.

PMID- 23165218
TI  - Biologic variation of copper, ceruloplasmin and copper/ceruloplasmin ratio
      (Cu:Cp) in serum.

PMID- 23165219
TI  - Haloperidol modulates midbrain-prefrontal functional connectivity in the rat
      brain.
AB  - Dopamine D2 receptor antagonists effectively reduce positive symptoms in
      schizophrenia, implicating abnormal dopaminergic neurotransmission as an
      underlying mechanism of psychosis. Despite the well-established, albeit
      incomplete, clinical efficacies of D2 antagonists, no studies have examined their
      effects on functional interaction between brain regions. We hypothesized that
      haloperidol, a widely used antipsychotic and D2 antagonist, would modulate
      functional connectivity in dopaminergic circuits. Ten male Sprague-Dawley rats
      received either haloperidol (1 mg/kg, s.c.) or the same volume of saline a week
      apart. Resting-state functional magnetic resonance imaging data were acquired 20
      min after injection. Connectivity analyses were performed using two complementary
      approaches: correlation analysis between 44 atlas-derived regions of interest,
      and seed-based connectivity mapping. In the presence of haloperidol, reduced
      correlation was observed between the substantia nigra and several brain regions,
      notably the cingulate and prefrontal cortices, posterodorsal hippocampus, ventral
      pallidum, and motor cortex. Haloperidol induced focal changes in functional
      connectivity were found to be the most strongly associated with ascending
      dopamine projections. These included reduced connectivity between the midbrain
      and the medial prefrontal cortex and hippocampus, possibly relating to its
      therapeutic action, and decreased coupling between substantia nigra and motor
      areas, which may reflect dyskinetic effects. These data may help in further
      characterizing the functional circuits modulated by antipsychotics that could be
      targeted by innovative drug treatments.

PMID- 23165220
TI  - MR imaging of the effects of methylphenidate on brain structure and function in
      attention-deficit/hyperactivity disorder.
AB  - Methylphenidate is the first-choice pharmacological intervention for the
      treatment of Attention-Deficit/Hyperactivity Disorder (ADHD). The pharmacological
      and behavioral effects of methylphenidate are well described, but less is known
      about neurochemical brain changes induced by methylphenidate. This level of
      analysis may be informative on how the behavioral effects of methylphenidate are
      established. This paper reviews structural and functional MRI studies that have
      investigated effects of methylphenidate in children with ADHD. Structural MRI
      studies provide evidence that long-term stimulant treatment may normalize
      structural brain changes found in the white matter, the anterior cingulate
      cortex, the thalamus, and the cerebellum in ADHD. Moreover, preliminary evidence
      suggests that methylphenidate treatment may normalize the trajectory of cortical
      development in ADHD. Functional MRI has provided evidence that methylphenidate
      administration has acute effects on brain functioning, and even suggests that
      methylphenidate may normalize brain activation patterns as well as functional
      connectivity in children with ADHD during cognitive control, attention, and
      during rest. The effects of methylphenidate on the developing brain appear highly
      specific and dependent on numerous factors, including biological factors such as
      genetic predispositions, subject-related factors such as age and symptom
      severity, and task-related factors such as task difficulty. Future studies on
      structural and functional brain changes in ADHD may benefit from inclusion
      strategies guided by current medication status and medication history. Further
      studies on the effects of methylphenidate treatment on structural and functional
      MRI parameters are needed to address unresolved issues of the long-term effects
      of treatment, as well as the mechanism through which medication-induced brain
      changes bring about clinical improvement. 

PMID- 23165222
TI  - Percutaneous fixation of thoracolumbar fractures: current concepts.
AB  - Numerous improvements in minimally invasive spine surgery (MISS) have been made
      during the last decade. MISS in thoracolumbar spine trauma management must
      achieve the same results as conventional treatment but with less morbidity. The
      increased use of MISS technologies in spine trauma has been correlated to the
      availability of more versatile instrumentation, which makes the fixation of all
      thoracic and lumbar levels possible. Balloon-assisted techniques have been used
      to support the anterior column in a stand-alone manner or in combination with
      open or percutaneous pedicle screw fixation. Fluoroscopy-assisted pedicle screw
      insertion is associated with less pedicle wall violation when compared to open
      surgery, but with increased radiation exposure for the surgeon and patient.
      Surgeons must be aware of this issue and new technologies are available to
      decrease irradiation. The advantages of percutaneous pedicle screw fixation
      relative to open surgery are discussed: preservation of posterior musculature,
      less blood loss, shorter operative time, lower infection risk, less postoperative
      pain, shorter rehabilitation time as well as shorter hospital stay. Limitations
      of percutaneous fixation include the inability to achieve direct spinal canal
      decompression and not having the option to perform a fusion. Nevertheless, these
      limitations can be addressed by combining MISS with open techniques. Indications
      for percutaneous spine fixation alone or in combination with MISS or open
      techniques are discussed based on the AO classification. The benefits of
      percutaneous spinal fixation for unstable spine fractures in polytrauma patients
      are also discussed. Posterior instrumentation can be easily removed after bone
      union to allow young patients to regain their mobility. Large well-controlled
      prospective studies are needed to draw up guidelines for less invasive procedures
      in spine trauma. In the future, development of new technologies can expand the
      scope of indications and treatment possibilities using MISS techniques in spine
      trauma.

PMID- 23165223
TI  - Reconstructing wholes from parts:  effects of modality, age, and hearing loss on
      word recognition.
AB  - OBJECTIVE: In this study, the effects of age, hearing loss, and modality on the
      ability to integrate partial information in degraded stimuli, either speech or
      text, were examined using isolated words. It was hypothesized that the ability to
      make use of partial information in speech diminishes with age. It was also
      hypothesized that additional contributions of cochlear pathology underlying
      hearing loss would be manifest as a further decrement in performance for older
      adults with hearing loss, relative to older adults with normal hearing.
      Furthermore, it was hypothesized that, if the ability to integrate partial
      information in speech is amodal, then recognition performance for degraded speech
      would be associated with recognition performance for parallel measures of
      degraded text. Last, it was hypothesized that, if the nature of the amodal
      ability to integrate partial information is cognitive, then the performance on
      auditory and visual measures of word recognition would be correlated with
      performance on measures of working memory. DESIGN: Twenty-five young adults with
      normal hearing, 20 older adults with normal hearing, and 21 older adults with
      hearing loss participated in this study. All participants completed three
      auditory and two parallel visual tasks consisting of listening to or reading
      degraded words or text. Older participants also completed a working-memory test
      battery. Group effects were examined for each of the auditory and visual
      measures. Performance of older participants on cognitive measures was compared
      with available data from a younger group participating in a different study in
      our laboratory (with similar protocol). Correlations between auditory and visual
      measures of speech recognition were examined for all participants. In addition,
      correlations between perceptual and cognitive measures were computed for the
      older participants. Finally, the relationship between dependent auditory measures
      and other independent measures in older adults were further examined using
      stepwise linear regression analyses. RESULTS: Of the 10 possible comparisons
      between the young and the two older groups for the five primary dependent
      measures, the young performed significantly better than the elderly did, 8 of the
      10 times. The two older groups performed similarly for most tasks. In young
      adults, performance among the auditory tasks and between the two visual tasks was
      significantly and moderately to strongly correlated. In addition, performance on
      one of the visual tasks was weakly to moderately significantly correlated with
      performance on each of the three auditory tasks. Similar moderate to strong
      correlations were found within the auditory and visual modalities in older
      adults. However, none of the between-modality correlations were significant in
      the elderly. CONCLUSIONS: In summary, the results of this study suggest that the
      ability to integrate partial information in degraded words diminishes with age.
      Once audibility is accounted for, this ability does not seem to diminish with
      cochlear pathology. In young adults, both modality-specific factors and amodal
      cognitive factors seem to contribute to this ability. In older adults, although
      modality-specific factors continue to be important, it seems that the perceptual
      mechanisms that underlie the processing of degraded speech and text are separate,
      at least for isolated words. Our results suggest that, when peripheral factors
      are accounted for, some higher-level, yet-to-be identified, age-related factors
      contribute to speech-communication difficulties in the elderly.

PMID- 23165224
TI  - Using a vocoder-based frequency-lowering method and spectral enhancement to
      improve place-of-articulation perception for hearing-impaired listeners.
AB  - OBJECTIVES: This study describes a vocoder-based frequency-lowering system that
      enhances spectral cues for nonsonorant consonants differing in place of
      articulation. The goal of this study was to evaluate the efficacy of this system
      for speech recognition by hearing-impaired listeners. DESIGN: Experiment 1
      evaluated fricative consonant recognition in quiet. Eight fricatives in /VCV/
      context were used. Experiment 2 evaluated consonant recognition in quiet with 22
      consonants. Six listeners with steeply sloping high-frequency sensorineural
      hearing loss participated in experiment 1. The same six listeners and three
      additional listeners with flat/mid-frequency sensorineural hearing loss
      participated in experiment 2. Two processing conditions-frequency lowering and
      conventional amplification-were tested in each experiment. Insertion gains based
      on the NAL-RP formula were provided up to 8000 Hz for each processing condition.
      In addition, speech stimuli were low-pass (LP) filtered at 1000, 1500, and 2000
      Hz to evaluate the effect of lack of high-frequency speech information on
      consonant perception with and without frequency lowering. For these LP speech
      conditions, amplification was provided up to the cutoff frequencies. Overall
      percent correct and percent information transmission were calculated for each
      processing and speech condition. RESULTS: The frequency-lowering system provided
      significant benefit for the perception of fricative consonants and perception of
      the place-of-articulation feature for hearing-impaired listeners without
      affecting their perception of sonorant consonants and other consonant features
      (i.e., voicing and nasality). The improvement of fricative consonant perception
      was observed for both wideband and LP speech conditions for the steeply sloping
      hearing-loss listeners. CONCLUSIONS: The results indicate that individuals with
      unaidable hearing loss above 1000 to 2000 Hz would receive significant benefit
      with the system compared with conventional amplification for the perception of
      fricative consonants, and more importantly, significant benefit for the
      perception of place of articulation.

PMID- 23165225
TI  - [Place of hand-held gamma-cameras in breast cancer].
AB  - Non-palpable breast cancers are more and more frequent. Their surgical management
      requires the excision of the tumor and sentinel lymph node (SLN) needing a
      technical preoperative organization combining preoperative identification of the
      tumor by wire guide and injection of a radioactive tracer for the identification
      of SLN. The implementation of this minimally invasive surgery is sometimes
      paradoxically complicated due to the presurgical organization requiring several
      medical teams. It is for this reason that hand-held gamma-cameras have been
      developed, used either preoperatively or during surgery to replace
      lymphoscintigraphy but also as a help to excision of the tumor after radioisotope
      injection. The objective of this study was to evaluate the interest of the main
      hand-held gamma-cameras used in breast cancer.

PMID- 23165226
TI  - [Feasibility of laparoendoscopic single-site surgery in gynecology with
      conventional laparoscopic instruments].
AB  - OBJECTIVES: To describe the safety and efficacy of single-port access for
      laparoscopic surgery in gynecology with conventional laparoscopic instruments.
      PATIENTS AND METHODS: In this prospective study, we report our experience with 90
      patients who underwent Single Port Access (SPA) laparoscopic surgery for
      gynecologic pathology with the use of the SILS((r)) Port Multiple Instrument
      Access Port (Covidien((r)), Mansfield, MA). RESULTS: We realised 15 ovarian
      cystectomies, 30 salpingo-oophrectomies with 14 one side, 9 lysis of adhesions, 7
      distal tubal repairs, 6 salpingectomy, 8 other procedures. The mean surgical time
      is 47 min (25-120). One conversion to conventional laparoscopy and one in
      laparotomy were performed. The mean duration stay is 2 days [1-3]. DISCUSSION AND
      CONCLUSION: SPA in gynecology is feasible with conventional laparoscopic
      instruments. SPA surgery represents the newest frontier in minimally invasive
      surgery.

PMID- 23165228
TI  - Eradication of Helicobacter pylori reduces metachronous gastric cancer after
      endoscopic resection of early gastric cancer.
AB  - BACKGROUND/AIMS: Although some studies have shown improvement of precancerous
      lesions and a decrease of metachronous gastric cancer after eradication of H.
      pylori, this is still controversial. METHODOLOGY: We identified 74 patients with
      early gastric cancer and who had their H. pylori eradicated after undergoing
      endoscopic resection between September, 2003 and September, 2010. The endoscopic
      biopsy specimens, campylobacter-like organism test and urea breath test were
      reviewed. Relapse of gastric cancer was assessed from medical records. RESULTS:
      Among the 74 patients, 61 (82.4%) were successfully eradicated. The mean duration
      of follow-up was 27.2+/-18.7 months. H. pylori colonization, neutrophil
      infiltration, mononuclear cell infiltration and intestinal metaplasia decreased
      after eradication (all p<0.05). For all the patients, metachronous gastric cancer
      showed a decrease in the eradicated group, but this did not reach statistical
      significance (odds ratio: 0.36, 95% CI: 0.08-1.70, p=0.189). However, when
      restricted to those who were followed-up for more than 18 months, metachronous
      gastric cancer was significantly decreased in the eradicated group (odds ratio:
      0.108, 95% CI: 0.016-0.726, p=0.035). CONCLUSIONS: Eradication of H. pylori
      decreased precancerous lesions, and when following-up for more than 18 months,
      eradication also reduced metachronous gastric cancer.

PMID- 23165229
TI  - Motion in radiotherapy: photon therapy.
AB  - This review considers the management of motion in photon radiation therapy. An
      overview is given of magnitudes and variability of motion of various structures
      and organs, and how the motion affects images by producing artifacts and
      blurring. Imaging of motion is described, including 4DCT and 4DPET. Techniques
      for monitoring motion in real time by use of surrogates are reviewed. Treatment
      planning for various motion-management treatment delivery strategies is
      discussed, including choice of planning image, treatment field margins and dose
      calculation. Imaging techniques displaying motion in the treatment room for pre
      treatment as well as real-time imaging for localization and verification are
      covered, and their use for various motion-management treatment delivery
      techniques is discussed. Use of motion management for different treatment sites
      breast, lung and other sites-is elaborated, and gating, breath-hold and beam
      tracking strategies are described. Suggestions are given for breast and lung for
      practicable protocols for routine clinical use of motion management, including
      decision strategies. Finally, a perspective of the future of motion management in
      photon radiation therapy is given.

PMID- 23165230
TI  - Solar fuels generation and molecular systems: is it homogeneous or heterogeneous
      catalysis?
AB  - Catalysis is a key enabling technology for solar fuel generation. A number of
      catalytic systems, either molecular/homogeneous or solid/heterogeneous, have been
      developed during the last few decades for both the reductive and oxidative multi
      electron reactions required for fuel production from water or CO(2) as renewable
      raw materials. While allowing for a fine tuning of the catalytic properties
      through ligand design, molecular approaches are frequently criticized because of
      the inherent fragility of the resulting catalysts, when exposed to extreme redox
      potentials. In a number of cases, it has been clearly established that the true
      catalytic species is heterogeneous in nature, arising from the transformation of
      the initial molecular species, which should rather be considered as a pre
      catalyst. Whether such a situation is general or not is a matter of debate in the
      community. In this review, covering water oxidation and reduction catalysts,
      involving noble and non-noble metal ions, we limit our discussion to the cases in
      which this issue has been directly and properly addressed as well as those
      requiring more confirmation. The methodologies proposed for discriminating
      homogeneous and heterogeneous catalysis are inspired in part by those previously
      discussed by Finke in the case of homogeneous hydrogenation reaction in
      organometallic chemistry [J. A. Widegren and R. G. Finke, J. Mol. Catal. A, 2003,
      198, 317-341].

PMID- 23165231
TI  - Early events in cell adhesion and polarity during epithelial-mesenchymal
      transition.

PMID- 23165232
TI  - Bandwidth-limited control and ringdown suppression in high-Q resonators.
AB  - We describe how the transient behavior of a tuned and matched resonator circuit
      and a ringdown suppression pulse may be integrated into an optimal control theory
      (OCT) pulse-design algorithm to derive control sequences with limited ringdown
      that perform a desired quantum operation in the presence of resonator distortions
      of the ideal waveform. Inclusion of ringdown suppression in numerical pulse
      optimizations significantly reduces spectrometer deadtime when using high quality
      factor (high-Q) resonators, leading to increased signal-to-noise ratio (SNR) and
      sensitivity of inductive measurements. To demonstrate the method, we
      experimentally measure the free-induction decay of an inhomogeneously broadened
      solid-state free radical spin system at high Q. The measurement is enabled by
      using a numerically optimized bandwidth-limited OCT pulse, including ringdown
      suppression, robust to variations in static and microwave field strengths. We
      also discuss the applications of pulse design in high-Q resonators to universal
      control of anisotropic-hyperfine coupled electron-nuclear spin systems via
      electron-only modulation even when the bandwidth of the resonator is
      significantly smaller than the hyperfine coupling strength. These results
      demonstrate how limitations imposed by linear response theory may be vastly
      exceeded when using a sufficiently accurate system model to optimize pulses of
      high complexity.

PMID- 23165233
TI  - Evaluation of the 2010 American Heart Association Guidelines for infant CPR
      finger/thumb positions for chest compression: a study using computed tomography.
AB  - INTRODUCTION: We sought to verify, using computed tomography (CT) examinations of
      infants, which the left ventricle (LV) is compressed and abdominal compression
      avoided by using the chest compression landmarks recommended by the 2010 American
      Heart Association (AHA) Guidelines for infant cardiopulmonary resuscitation
      (CPR). METHODS: Using CT examinations of 63 infants performed between March 2002
      and July 2011, we retrospectively measured the distance between the INL and the
      xiphoid process, and the distance of the lower third (LT) of the sternum. The
      distances between LV maximal diameter (LVMD) and xiphoid processes were also
      measured to determine whether LVs would be compressed by chest compressions.
      These distances were compared with the finger placements by 20 adults, when
      placed on infant mannequins for simulated two-finger or two-thumb infant CPR.
      RESULTS: The mean distances of the INL and the LT of the sternum were 32 +/- 8 mm
      and 12 +/- 2 mm from the xiphoid, respectively. The LVMD was placed 15 +/- 6 mm
      from the xiphoid process. When we overlaid the width of adult finger placement (a
      mean of 28 mm for two-finger technique, and 23 mm for two-thumb technique), the
      LV was compressed in 57 patients (90.5%) and 59 patients (93.7%), respectively.
      The upper abdomen was compressed in 22 patients (34.9%) by the two-finger
      technique and in 16 patients (25.3%) by the two-thumb technique with the range of
      0.3-10.8mm. CONCLUSION: When applying the 2010 AHA Guidelines for infant CPR,
      recommended finger placement allows for adequate compression of the LV in more
      than 90% of patients. In 23-35% of infants, the upper abdomen is compressed from
      0.3mm to 10.7 mm.

PMID- 23165234
TI  - Colorectal cancer: CRC--all about microbial products and barrier function?

PMID- 23165238
TI  - Gallbladder: Loss of interstitial Cajal-like cells in the gallbladder might
      contribute to gallstone formation.

PMID- 23165237
TI  - Management of subcentimetric polyps detected by CT colonography.
AB  - The advent of CT colonography (CTC) has generated conservative policies for the
      management of diminutive (<5 mm) and small (6-9 mm) polyps to prevent inefficient
      duplication of screening tests. The effect of not referring subcentimetric polyps
      for polypectomy on the efficacy of colorectal cancer screening is still uncertain
      but depends on the natural history of diminutive and small polyps, as well as on
      the distribution of advanced neoplasia within these lesions. Simulation modelling
      enables the efficacy and cost-effectiveness of conservative strategies for the
      management of subcentimetric lesions to be tested (such as nonreferral to
      polypectomy for diminutive polyps and early CTC surveillance for small polyps).
      These policies might be further refined by the inclusion of patient and polyp
      related predictive factors for advanced neoplasia, enabling a patient-tailored
      approach for the management of these lesions.

PMID- 23165235
TI  - The role of microRNAs in cancers of the upper gastrointestinal tract.
AB  - Cancers of the oesophagus, gastro-oesophageal junction and stomach (upper
      gastrointestinal tract cancers; UGICs) pose a major health risk around the world.
      Collectively, the 5-year survival rate has remained <15%, and therapeutic
      improvements have been very slow and small. Novel molecules for early diagnosis,
      prognosis and therapy are, therefore, urgently needed. The role that microRNA
      (miRNA) molecules have in UGICs are worth pursuing to this end. miRNAs are small
      noncoding RNA molecules that regulate ~60% of coding genes in humans and,
      therefore, are pivotal in mediating and regulating many physiologic processes.
      miRNAs are deregulated in many disease states, particularly in cancer, making
      them important targets. Here, we review the growing body of evidence regarding
      the alterations of miRNAs in UGICs. By suppressing translation and/or promoting
      degradation of mRNAs, miRNAs can contribute to carcinogenesis and progression of
      UGICs. In-depth studies of miRNAs in UGICs might yield novel insights and
      potential novel therapeutic strategies.

PMID- 23165239
TI  - IBD: Elafin--a potential IBD therapy.

PMID- 23165240
TI  - Sulfonic acid functionalized nano gamma-Al2O3 catalyzed per-O-acetylated of
      carbohydrates.
AB  - A simple and clean synthesis of per-O-acetylation carbohydrate derivatives has
      been accomplished by treatment of sugars with a stoichiometric quantity of acetic
      anhydride under solvent-free conditions in the presence of sulfonic acid
      functionalized nano gamma-Al(2)O(3) as an efficient and environmentally benign
      catalyst.

PMID- 23165236
TI  - The digestive neuronal-glial-epithelial unit: a new actor in gut health and
      disease.
AB  - The monolayer of columnar epithelial cells lining the gastrointestinal tract--the
      intestinal epithelial barrier (IEB)--is the largest exchange surface between the
      body and the external environment. The permeability of the IEB has a central role
      in the regulation of fluid and nutrient intake as well as in the control of the
      passage of pathogens. The functions of the IEB are highly regulated by luminal as
      well as internal components, such as bacteria or immune cells, respectively.
      Evidence indicates that two cell types of the enteric nervous system (ENS),
      namely enteric neurons and enteric glial cells, are potent modulators of IEB
      functions, giving rise to the novel concept of a digestive 'neuronal-glial
      epithelial unit' akin to the neuronal-glial-endothelial unit in the brain. In
      this Review, we summarize findings demonstrating that the ENS is a key regulator
      of IEB function and is actively involved in pathologies associated with altered
      barrier function.

PMID- 23165241
TI  - First ever isolation of bacterial prolipoprotein diacylglyceryl transferase in
      single step from Lactococcus lactis.
AB  - The unique bacterial enzyme phosphatidylglycerol: prolipoprotein diacylglyceryl
      transferase (Lgt) is the least studied enzyme of the ubiquitous bacterial
      lipoprotein synthetic pathway, mostly due to the low abundance of the enzyme. So
      far, Lgt has been studied to a limited extent in gram-negative bacteria, mainly
      in Escherichia coli. We, for the first time, report the isolation of an adequate
      amount of Lgt from the gram-positive lactic acid bacteria, Lactococcus lactis and
      compare this wild-type bacterial enzyme with the E. coli enzyme. The L. lactis
      Lgt, when purified by cationic-exchange chromatography, showed a 20-fold increase
      in the specific activity compared to that of the load, and 75% of the total Lgt
      activity loaded was recovered. Kinetically, L. lactis Lgt was found to be similar
      to the E. coli enzyme with matching K(m) and V(max), whereas the specific
      activity of the L. lactis enzyme was about 20 times less than that of the E. coli
      enzyme. Comparative bioinformatic analysis of L. lactis, E. coli and
      Staphylococcus aureus Lgt revealed that the conserved and catalytically important
      His-103 residue in E. coli Lgt, was altered to Tyr in L. lactis. Investigations
      showed that other bacteria where this alteration is visible, form a diversion
      within the gram-positive bacteria in evolution. Further analysis revealed
      Mycobacterium smegmatis to be the species which evolved with the alteration of
      His to Tyr.

PMID- 23165242
TI  - Visualization of clusters in polymer electrolyte membranes by electron
      microscopy.
AB  - The morphology of ionic clusters that form in polyelectrolyte membranes has a
      strong effect on transport and electrical properties. In spite of considerable
      research effort the link between morphology and properties has not been clearly
      established, mainly due to difficulties in assessing nanoscale morphology.
      Electron microscopy (EM) has the potential to visualize morphology. However
      success in visualization has so far been moderate. In this review we focus on the
      potential of EM techniques to characterize the ionic domains. We use both
      experimental data and models to compare the capabilities of several EM
      techniques: BF TEM, HAADF, core-loss EELS, and low-loss EELS in projection
      imaging and STEM modes. The main problems common for all these EM modes are
      radiation damage and overlap of features in projection. Our models show that core
      loss EELS with exposures that are below the typical damage threshold is incapable
      of resolving 2 nm diameter sulfur-rich clusters in PEMs. While low loss EELS
      requires lower exposure, the insight it can provide is quite limited. HAADF and
      BF TEM present the most effective modes for imaging the sulfur clusters in PEMs.
      While BF TEM uses scattered electrons more efficiently, HAADF using slightly
      higher doses can provide unique information due to in-focus imaging and
      transparent interpretation of the images. Fortunately, in at least some
      interesting cases the clusters themselves are much more radiation resistant than
      the polymer and can be studied at exposures high enough to obtain clear images.
      Our simulations also show that tomographic 3D reconstruction provides the best
      approach for solving the overlap problem. In spite of the abilities of electron
      tomography, data obtained from all EM techniques improve if thin sections are
      studied. We briefly discuss methods for obtaining such sections.

PMID- 23165244
TI  - Surfactant-free synthesis of Fe3O4@PANI and Fe3O4@PPy microspheres as adsorbents
      for isolation of PCR-ready DNA.
AB  - Magnetic separation with composite microspheres presents an alternative strategy
      for applications in biomedical and bioengineering fields. However, the synthesis
      of core-shell structured magnetic composites universally assumes the surfactant
      directing and/or silica-assisting polymerization approach to modify and stabilize
      the magnetic cores. In this paper, we report on the surfactant-free synthesis of
      well-defined core-shell structured Fe(3)O(4)@PANI and Fe(3)O(4)@PPy microspheres
      with high magnetization. The temperature dependence of magnetization of the
      samples was examined as a function of temperature between 3 and 300 K in an
      applied field of 500 Oe. It was found that the blocking temperature (T(B)) values
      of the composite spheres are well above the room temperature. The small variation
      in magnetization as the temperature changes renders the composite spheres a
      suitable candidate when used at elevated temperatures. Also, the genomic DNA can
      be effectively isolated from Aspergillus niger (A. niger) cells with the
      composite microspheres, using a PEG-NaCl binding buffer and a phosphate eluting
      buffer. The magnetic isolation of genomic DNA with the composite microspheres was
      shown to be superior to the conventional phenol-chloroform extraction, which was
      confirmed by agarose gel eletrophoresis and polymerase chain reaction (PCR)
      diagnosis. The Fe(3)O(4)@PANI and Fe(3)O(4)@PPy microspheres presented here have
      great potential in enzyme immobilization, drug delivery, catalysis, and sensors.

PMID- 23165246
TI  - The role of head stabilization in locomotion in children with cerebral palsy.
AB  - OBJECTIVE: The objective of the present study was to highlight the role of head
      stabilization and to analyze multisegment head-trunk coordination during gait in
      children with cerebral palsy (CP). MATERIAL AND METHOD: Postural control was
      measured and compared in a group of 16 CP subjects and a control group of 16
      healthy subjects. The subjects had to walk along an out-and-back course at their
      freely chosen gait speed. For each gait cycle, motion analysis techniques were
      used to calculate the amplitude of the head angle (relative to the trunk) in the
      sagittal and frontal planes. RESULTS: Kinematic analysis revealed a number of
      significant intergroup differences, with a more pronounced variation in the head
      angle (relative to the trunk) in the CP group than in the control group. There
      were no significant intergroup differences in terms of the angular amplitude of
      the head in the sagittal plane. CONCLUSION: The greater variability of the head
      angle in the frontal plane in the CP subjects might reflect the presence of
      greater head roll as a compensatory strategy. These finding suggest that the
      clinical evaluation of posture during gait in children with CP should be
      reconsidered.

PMID- 23165243
TI  - p63 the guardian of human reproduction.
AB  - p63 is a transcriptional factor implicated in cancer and development. The
      presence in TP63 gene of alternative promoters allows expression of one isoform
      containing the N-terminal transactivation domain (TA isoform) and one N-terminal
      truncated isoform (DeltaN isoform). Complete ablation of all p63 isoforms
      produced mice with fatal developmental abnormalities, including lack of epidermal
      barrier, limbs and other epidermal appendages. Specific TAp63-null mice, although
      they developed normally, failed to undergo in DNA damage-induced apoptosis during
      primordial follicle meiotic arrest, suggesting a p63 involvement in maternal
      reproduction. Recent findings have elucidated the role in DNA damage response of
      a novel Hominidae p63 isoform, GTAp63, specifically expressed in human spermatic
      precursors. Thus, these findings suggest a unique strategy of p63 gene, to evolve
      in order to preserve the species as a guardian of reproduction. Elucidation of
      the biological basis of p63 function in reproduction may provide novel approaches
      to the control of human fertility.

PMID- 23165247
TI  - Raman scattering evidence of hydrohalite formation on frozen yeast cells.
AB  - We studied yeast cells in physiological solution during freezing by Raman
      microspectroscopy technique. The purpose was to find out the origin of a sharp
      peak near ~3430cm(-1) in Raman spectrum of frozen mammalian cells, observed
      earlier (J. Dong et al., Biophys. J. 99 (2010) 2453), which presumably could be
      used as an indicator of intracellar ice appearance. We have shown that this line
      (actually doublet of 3408 and 3425cm(-1)) corresponds to Raman spectrum of
      hydrohalite (NaCl?2H(2)O), which is formed as the result of the eutectic
      crystallization of the liquid solution around the cells. We also show that the
      spatial distribution of hydrohalite in the sample significantly depends on the
      cooling rate. At lower cooling rate (1 degrees C/min), products of eutectic
      crystallization form layer on the cell surface which thickness varies for
      different cells and can reach ~1MUm in thickness. At higher cooling rate (20
      degrees C/min), the hydrohalite distribution appears more homogeneous, in the
      sample, and the eutectic crystallization layer around the cells was estimated to
      be less than ~20nm. These experimental results are consistent with scenarios
      predicted by the two-factor hypothesis for freezing induced cell injury. This
      work demonstrates a potential of Raman microspectroscopy to study peculiarities
      of the eutectic crystallization around single cells in vivo with the high spatial
      resolution.

PMID- 23165249
TI  - Titanium pyridonates and amidates: novel catalysts for the synthesis of random
      copolymers.
AB  - A series of pyridonate and amidate supported titanium alkoxides have been
      isolated. These complexes can be readily prepared in high yield, under mild
      reaction conditions in only two steps from commercially available
      (Ti(NMe(2))(4)). We have furnished one of the rare examples of discrete catalysts
      for random copolymer synthesis.

PMID- 23165248
TI  - Postmortem serum levels of amylase and gamma glutamyl transferase (GGT) as
      markers of systemic tissue damage in forensic autopsy.
AB  - Serum amylase (AMY) and gamma glutamyl transferase (GGT) are routine clinical
      markers for investigating pancreatic and hepatobiliary disorders, respectively,
      but are also increased in systemic deterioration following critical trauma and
      diseases. The present study investigated the postmortem levels in bilateral
      cardiac blood of medicolegal autopsy cases without decomposition (n=163),
      excluding those with pancreatic or hepatic injury, or preexisting pathologies, as
      well as prolonged death cases, to evaluate the changes due to systemic
      deterioration in the death process after fatal insults with special regard to
      intoxication, hyperthermia (heatstroke) and hypothermia (cold exposure). Serum
      AMY and GGT levels were virtually independent of postmortem interval. Serum AMY
      level was mostly higher than the clinical reference range, predominantly
      including salivary fractions, but was usually below 1000U/L except for fatal
      intoxication, which showed significant increases of total AMY as well as salivary
      and pancreatic fractions in bilateral cardiac blood. Serum levels of salivary and
      pancreatic AMY fractions showed tendencies to be related to pancreatic
      subcapsular and interstitial bleeding, respectively, which were relatively
      frequent and evident in mechanical asphyxiation, intoxication and hyperthermia
      (heatstroke). Serum GGT was often elevated (mostly below 300U/L) in cases other
      than hypothermia (cold exposure). These findings suggest postmortem serum AMY and
      GGT as indicators of the severity of systemic organ damage in death processes,
      especially in intoxication; however, elevated serum AMY and GGT levels over 1000
      and 300U/L might indicate significant pancreatic and hepatobiliary pathologies,
      respectively, except for an elevated serum AMY level in intoxication.

PMID- 23165251
TI  - Synaptic plasticity: Neuroligin 1 does the splits.

PMID- 23165250
TI  - Rare extragonadal teratomas in children: complete tumor excision as a reliable
      and essential procedure for significant survival. Clinical experience and review
      of the literature.
AB  - BACKGROUND: Extragonadal teratomas are rare tumors in neonates and infants and
      can sometimes show unusual, distinctive feature such as an unusual location, a
      clinical sometimes acute, presentation and a "fetiform" histotype of the lesion.
      We have extrapolated, from our entire experience of teratomas, 4 unusual cases,
      mostly operated as emergencies; 2 of them were treated just after birth. Aim of
      this paper is to report the clinical and pathological findings, to evaluate the
      surgical approach and the long-term biological behaviour in these cases, in the
      light of survival and current insights reported in the literature. MATERIAL AND
      METHODS: The Authors reviewed the most significant (Tables I and II) clinical,
      laboratory, radiologic, and pathologic findings, surgical procedures, early and
      long-term results in 4 children, 1 male and 3 females (M/F ratio: 1/3), suffering
      from extragonadal teratomas, located in the temporo-zygomatic region of the head
      (Case n. 1, Fig. 1), retroperitoneal space (Case n. 2, Fig. 2) ,liver (Case n. 3,
      Figg. 3-5), kidney (Case n. 4, Fig. 6, 7), respectively. Of the 4 patients, 2
      were treated neonatally (1 T. of the head, 1 retroperitoneal T.) A prenatal
      diagnosis had already been made in 2 of the 4 patients, between the 2nd and 3rd
      trimester of pregnancy, All the infants were born by scheduled caesarean section
      in a tertiary care hospital and were the immediately referred to thew N.I.C.Us.
      Because of a mostly acute clinical presentation, the 4 patients were then
      referred to the surgical unit at different ages: 7 days, 28 days, 7 months, and 4
      years respectively. The initial clinical presentation (Table II) was consistent
      with the site of the mass and/or its side effects. The 2 newborns (Case 1 and 2)
      both with a prenatally diagnosed mass located at the temporozygomatic region and
      in the abdominal cavite respectively, already displayed, at birth a mass with a
      tendency to further growth. The symptoms and signs described to the primary care
      physician by the parents of the 2 patients suffering from intra-abdominal tumours
      (Cases n. 3, 4) were: swelling of the epigastrium and left hypochondrium due to a
      progressively growing hard mass, without impairment of the general, conditions in
      case n.3 (teratoma of the liver),while recurrent abdominal pain lasting for the 5
      months was described in case n.4(retroperitoneal teratoma), followed by the
      development of an evident hard mass occupying the entire abdomen. In this case
      the symptoms suddenly worsened, with acute pain extending to the entire abdomen,
      high fever (>39 degrees  C), polypnea, anemia, deterioration of the general
      conditions and a rapid further enlargement of the mass. Antibiotic therapy was
      ansuccessful. The young child underwent a radiologic investigation (Fig. 6) that
      showed a large calcified mass in the left retroperitoneal space, associated with
      pleural effusion, In all the patients except for the Case n. 3, emergency
      surgical management was required and, in accordance with recommended practice,
      the procedure was complete exeresis. RESULTS (TABLE I): All the 4 patients had an
      uneventful postoperative course. Clinical surveillance and tests of AFP and other
      markers were scheduled every 6 months for the first years and annually
      thereafter. At the current date they are alive, disease-free and have not
      suffered any recurrence with a follow-up as reported in Table I, of 7 years in
      case n. 2; 23 years in case n. 1; 42 years in case n. 3 and 36 years in case n.
      4. CONCLUSIONS: Some extragonadal teratomas of childhood of may rarely arise in
      the solid organs (liver, kidney), in the retroperitoneal space or the cranio
      facial region, and also show unique histotype childhood characteristics
      ("fetiform") which distinguish them from more common cases. Being congenital
      tumours, prenatal diagnosis by US scan is extremely important in order to
      organize proper perinatal care in appropriate facilities where it is possible to
      define the diagnosis and carry out emergency surgery. An emergency procedure is
      frequently dictated both by complications related to the mass eddect and by the
      need to define the histology of the whole mass rather than just small biopsy
      specimens, Some teratomatas can hide more or less extensive islands of immaturity
      signs of malignant transformation that are clinically evident. It should be
      remembered that high serum levels of alpha-fetoprotein and calcficationof the
      imaging study, that are usually pathognomonic elements for fiagnosis, nay be
      lacking in abdominal lesions. Moreover, some additional specific diagnostic
      problems can be faced by either the radiologist (differential diagnosis from
      acquired or congenital cystic lesions, identification of the primary site of
      origin in the liver kidney or retroperitoneal space). Or the histopathologist
      (exclusion of renal metastasis of a primary gonadal teratomas of a glomerular and
      tubular differentiation a Wilm's tumour). The prognosis is generally benign,
      although the AIEOP guideline pointed out that high levels of circulating markers,
      including AFP, in children affected by mature or immature teratomas, could
      indicate rhe presence of micro-foci of YST, marking them out as at high risk. The
      UKCCSG II and the SFOP indicates AFP values exceeding 10,000 ng/ml as the
      threshold identifying a group of patients with a severe prognosis. The treatment
      indicated is early, complete exeresis, followed by a careful, exstensive,
      microscopic examination, associated, if necessary, with adjuvant chemotherapy.
      Finally, to improve the prognosis, close, long-term clinical, laboratory and
      imaging surveillance is necessary, at shorter intervals during the first 5 years
      after the exeresis and annually thereafter.

PMID- 23165252
TI  - Spatial processing: Monkey brains make space for grid cells.

PMID- 23165253
TI  - Reward: Finding the paths to food reward.

PMID- 23165254
TI  - Behavioural neuroscience: Ancient behavioural modulators.

PMID- 23165259
TI  - Separated at birth? The functional and molecular divergence of OLIG1 and OLIG2.
AB  - The basic helix-loop-helix transcription factors oligodendrocyte transcription
      factor 1 (OLIG1) and OLIG2 are structurally similar and, to a first
      approximation, coordinately expressed in the developing CNS and postnatal brain.
      Despite these similarities, it was apparent from early on after their discovery
      that OLIG1 and OLIG2 have non-overlapping developmental functions in patterning,
      neuron subtype specification and the formation of oligodendrocytes. Here, we
      summarize more recent insights into the separate roles of these transcription
      factors in the postnatal brain during repair processes and in neurological
      disease states, including multiple sclerosis and malignant glioma. We discuss how
      the unique functions of OLIG1 and OLIG2 may reflect their distinct genetic
      targets, co-regulator proteins and/or post-translational modifications.

PMID- 23165260
TI  - Encoding asymmetry within neural circuits.
AB  - Genetic and environmental factors control morphological and functional
      differences between the two sides of the nervous system. Neural asymmetries are
      proposed to have important roles in circuit physiology, cognition and species
      specific behaviours. We propose two fundamentally different mechanisms for
      encoding left-right asymmetry in neural circuits. In the first, asymmetric
      circuits share common components; in the second, there are unique unilateral
      structures. Research in both vertebrates and invertebrates is helping to reveal
      the mechanisms underlying the development of neural lateralization, but less is
      known about the function of circuit asymmetries. Technical advances in the coming
      years are likely to revolutionize our understanding of left-right asymmetry in
      the nervous system.

PMID- 23165261
TI  - Down syndrome: the brain in trisomic mode.
AB  - Down syndrome is the most common form of intellectual disability and results from
      one of the most complex genetic perturbations that is compatible with survival,
      trisomy 21. The study of brain dysfunction in this disorder has largely been
      based on a gene discovery approach, but we are now moving into an era of
      functional genome exploration, in which the effects of individual genes are being
      studied alongside the effects of deregulated non-coding genetic elements and
      epigenetic influences. Also, new data from functional neuroimaging studies are
      challenging our views of the cognitive phenotypes associated with Down syndrome
      and their pathophysiological correlates. These advances hold promise for the
      development of treatments for intellectual disability.

PMID- 23165262
TI  - Sex differences in pain and pain inhibition: multiple explanations of a
      controversial phenomenon.
AB  - A clear majority of patients with chronic pain are women; however, it has been
      surprisingly difficult to determine whether this sex bias corresponds to actual
      sex differences in pain sensitivity. A survey of the currently available
      epidemiological and laboratory data indicates that the evidence for clinical and
      experimental sex differences in pain is overwhelming. Various explanations for
      this phenomenon have been given, ranging from experiential and sociocultural
      differences in pain experience between men and women to hormonally and
      genetically driven sex differences in brain neurochemistry.

PMID- 23165264
TI  - Integrating clinical medicine into biomedical graduate education to promote
      translational research: strategies from two new PhD programs.
AB  - For several decades, a barrier has existed between research and clinical
      medicine, making it difficult for aspiring scientists to gain exposure to human
      pathophysiology and access to clinical/translational research mentors during
      their graduate training. In 2005, the Howard Hughes Medical Institute announced
      the Med Into Grad initiative to support graduate programs that integrate clinical
      knowledge into PhD biomedical training, with the goal of preparing a new cadre of
      translational researchers to work at the interface of the basic sciences and
      clinical medicine. Two institutions, Baylor College of Medicine and the Cleveland
      Clinic/Case Western Reserve University, developed new PhD programs in
      translational biology and/or molecular medicine. These programs teach the topics
      and skills that today's translational researchers must learn and expose students
      to clinical medicine. In this article, the authors compare and contrast the
      history, implementation, and evaluation of the Translational Biology and
      Molecular Medicine program at Baylor College of Medicine and the Molecular
      Medicine program at the Cleveland Clinic/Case Western Reserve University. The
      authors also demonstrate the feasibility of creating a multidisciplinary graduate
      program in molecular medicine that integrates pathophysiology and clinical
      medicine without extending training time. They conclude with a discussion of the
      similarities in training approaches that exist despite the fact that each program
      was independently developed and offer observations that emerged during their
      collaboration that may benefit others who are considering developing similar
      programs.

PMID- 23165263
TI  - The mechanobiology of brain function.
AB  - All cells are influenced by mechanical forces. In the brain, force-generating and
      load-bearing proteins twist, turn, ratchet, flex, compress, expand and bend to
      mediate neuronal signalling and plasticity. Although the functions of
      mechanosensitive proteins have been thoroughly described in classical sensory
      systems, the effects of endogenous mechanical energy on cellular function in the
      brain have received less attention, and many working models in neuroscience do
      not currently integrate principles of cellular mechanics. An understanding of
      cellular-mechanical concepts is essential to allow the integration of
      mechanobiology into ongoing studies of brain structure and function.

PMID- 23165265
TI  - Assessing the evolving definition of underrepresented minority and its
      application in academic medicine.
AB  - PURPOSE: To assess how U.S. academic health centers (AHCs) define the term
      underrepresented minority (URM) and apply it to their diversity programs,
      following the 2003 revision of the Association of American Medical Colleges'
      (AAMC's) definition of URM. METHOD: In 2010, the authors developed and deployed a
      cross-sectional survey of diversity leaders at 106 AHCs. The survey included
      questions about the diversity leader and institution's diversity program;
      institution's URM definition; application of that definition; and the diversity
      leader's perceptions of the representation and institutional contribution of
      various ethnic/racial groups. The authors used descriptive statistics to analyze
      the results. RESULTS: Of the 106 diversity leaders invited, 89 (84.0%) responded
      and 78 (73.6%) provided a working definition of URM. Most programs (40/78; 51%)
      used the 2003 AAMC definition of URM, which includes racial/ethnic groups that
      are underrepresented in medicine relative to local and national demographics.
      Only 14.1% (11/78) used the pre-2003 AAMC definition, which included only African
      Americans, Mexican Americans, Native Americans, and mainland Puerto Ricans.
      Approximately one-third (23/78; 29.5%) also considered other diversity factors,
      such as socioeconomic status, sexual orientation, and disability, in defining
      URM. Fifty-eight respondents (74.4%) confirmed that their diversity programs
      targeted specific groups. CONCLUSIONS: The definition of URM used by diversity
      programs at U.S. AHCs varied widely. Although some classified URMs by
      racial/ethnic categories, the majority defined URM more broadly to encompass
      other demographic and personal characteristics. This shift should prepare
      academic medicine to eliminate health disparities and meet the health needs of an
      increasingly diverse population.

PMID- 23165266
TI  - Characteristics of successful and failed mentoring relationships:  a qualitative
      study across two academic health centers.
AB  - PURPOSE: To explore the mentor-mentee relationship with a focus on determining
      the characteristics of effective mentors and mentees and understanding the
      factors influencing successful and failed mentoring relationships. METHOD: The
      authors completed a qualitative study through the Departments of Medicine at the
      University of Toronto Faculty of Medicine and the University of California, San
      Francisco, School of Medicine between March 2010 and January 2011. They conducted
      individual, semistructured interviews with faculty members from different career
      streams and ranks and analyzed transcripts of the interviews, drawing on grounded
      theory. RESULTS: The authors completed interviews with 54 faculty members and
      identified a number of themes, including the characteristics of effective mentors
      and mentees, actions of effective mentors, characteristics of successful and
      failed mentoring relationships, and tactics for successful mentoring
      relationships. Successful mentoring relationships were characterized by
      reciprocity, mutual respect, clear expectations, personal connection, and shared
      values. Failed mentoring relationships were characterized by poor communication,
      lack of commitment, personality differences, perceived (or real) competition,
      conflicts of interest, and the mentor's lack of experience. CONCLUSIONS:
      Successful mentorship is vital to career success and satisfaction for both
      mentors and mentees. Yet challenges continue to inhibit faculty members from
      receiving effective mentorship. Given the importance of mentorship on faculty
      members' careers, future studies must address the association between a failed
      mentoring relationship and a faculty member's career success, how to assess
      different approaches to mediating failed mentoring relationships, and how to
      evaluate strategies for effective mentorship throughout a faculty member's
      career.

PMID- 23165267
TI  - Remediation of residents in difficulty:  a retrospective 10-year review of the
      experience of a postgraduate board of examiners.
AB  - PURPOSE: To determine, through a 10-year review, (1) the prevalence of residents
      in difficulty, (2) characteristics of these residents, (3) areas of residents'
      weakness, and (4) outcomes of residents who undergo remediation. METHOD: A
      retrospective review of resident records for the University of Toronto Faculty of
      Medicine's (UT-FOM) Board of Examiners for Postgraduate Programs (BOE-PG) was
      done from July 1, 1999 to June 30, 2009 using predetermined data elements entered
      into a standardized form and analyzed for trends and significance. Outcomes for
      residents in difficulty were tracked through university registration systems and
      licensure databases. RESULTS: During 10 years, 103 UT-FOM residents were referred
      to the BOE-PG, representing 3% of all residents enrolled. The annual prevalence
      of residents referred to the BOE-PG ranged from 0.2% to 1.5%. The CanMEDS
      framework was used to classify areas of residents' weaknesses and organize
      remediation plans. All 100 residents studied had either medical expertise (85%)
      or professionalism (15%) weaknesses or both. Residents had difficulties with an
      average of 2.6 CanMEDS Roles, with highest frequencies of Medical Expert (85%)
      Professional (51%), Communicator (49%), Manager (43%), and Collaborator (20%).
      Often, there were multiple remediation periods, with an average of six months'
      duration. Usually, remediation was successful; 78% completed residency education,
      17% were unsuccessful, and 5% remained in training. CONCLUSION: Residents in
      difficulty have multiple areas of weakness. The CanMEDS framework is an effective
      approach to classifying problems and designing remediation plans. Successful
      completion of residency education after remediation is the most common outcome.

PMID- 23165268
TI  - Perspective: One Health: a compelling convergence.
AB  - One Health has been defined as "the collaborative effort of multiple disciplines-
      working locally, nationally, and globally--to attain optimal health for people,
      animals, plants, and our environment." The broadly based One Health movement
      includes domains as diverse as agricultural and animal science, environmental
      science, climatology, veterinary medicine, human medicine, and public health. One
      Health, previously espoused by Virchow, Osler, and other pioneers in medical
      education, is not a new idea, but, as an approach for dealing with the many
      global health problems in an increasingly interconnected world, it has become
      more important than ever. The 1999 North American West Nile virus epidemic
      illustrates that pathogens can, and frequently do, have major effects on animal
      and human populations simultaneously and that the interface between humans and
      animals is frequently the source of new or resurgent diseases. Further, climate
      change will result in widespread alterations to environmental conditions
      worldwide. How humanity addresses the resulting challenges to human and animal
      health as well as to the world's water and food supplies will have a major impact
      on how, or even if, the global community survives.One Health touches on all the
      missions of academic health centers: population or public health, the care of
      individual patients, biomedical research, and health education. Texas A&M
      University is working to break down the barriers that have impeded collaboration
      among the scientific disciplines now encompassed under the One Health banner to
      create a whole greater than the sum of its component parts.

PMID- 23165269
TI  - Perspective: Teaching and mentoring the history of medicine: an Oslerian
      perspective.
AB  - Many predict a takeover (seen by some as hostile, and by others as inadvertent)
      of professional virtues and values by government and capitalism. One source of
      professional virtues and values consists of lessons from the history of medicine
      as taught and mentored by Sir William Osler. Some medical schools have required
      courses in medical history, but proposing a new requirement would probably be a
      tough sell to most curriculum committees. Osler himself argued against compulsory
      courses in medical history. The authors propose that exposing medical students to
      the history of medicine promotes at least two of the seven types of
      professionalism identified by Hafferty and Castellani. Exposure to the evolution
      of medical science and to exemplary physicians of bygone eras promotes nostalgic
      professionalism, which, although in some ways suspect and naive, fosters a sense
      of belonging and solidarity as members of a profession, not a trade, whereas
      exposure to the evolution of medicine as a public service, to the sad history of
      health care disparities, and to patients' perspectives promotes activist
      professionalism, fostering a sense of civic responsibility and opposition to
      excessive commercialism.Steps to promote such exposure include (1) identifying
      faculty, community physicians, and others interested in the history of medicine,
      (2) including the history of medicine in faculty development programs, (3)
      considering a segment in the history of medicine during the introduction to each
      major course, (4) sponsoring history clubs, and (5) promoting environments
      favorable for mentor-protege relationships for faculty and students with further
      interest.

PMID- 23165270
TI  - Perspective: Entering uncharted waters: navigating the transition from trainee to
      career for the nonphysician clinician-scientist.
AB  - The transition from trainee to career clinician-scientist can be a stressful and
      challenging time, particularly for those entering the less established role of
      nonphysician clinician-scientist. These individuals are typically PhD-prepared
      clinicians in the allied health professions, who have either a formal or informal
      joint appointment between a clinical institution and an academic or research
      institution. The often poorly defined boundaries and expectations of these
      developing roles can pose additional challenges for the trainee-to-career
      transition.It is important for these trainees to consider what they want and need
      in a position in order to be successful, productive, and fulfilled in both their
      professional and personal lives. It is also critical for potential employers,
      whether academic or clinical (or a combination of both), to be fully aware of the
      supports and tools necessary to recruit and retain new nonphysician clinician
      scientists. Issues of relevance to the trainee and the employer include finding
      and negotiating a position; the importance of mentorship; the value of effective
      time management, particularly managing clinical and academic time commitments;
      and achieving work-life balance. Attention to these issues, by both the trainee
      and those in a position to hire them, will facilitate a smooth transition to the
      nonphysician clinician-scientist role and ultimately contribute to individual and
      organizational success.

PMID- 23165271
TI  - Structured global health programs in U.S. medical schools: a web-based review of
      certificates, tracks, and concentrations.
AB  - PURPOSE: To determine the prevalence and requirements of structured,
      longitudinal, nondegree global health (GH) programs (e.g., certificates, tracks,
      concentrations) in U.S. MD-granting medical schools. METHOD: In March 2011, two
      reviewers independently searched the Web sites of all 133 U.S. MD-granting
      medical schools and reviewed Google search results seeking evidence of,
      information about, and the requirements of structured GH programs. The authors
      excluded programs that were not open to medical students, granted a degree,
      and/or required medical students to extend training time. RESULTS: Of 133
      institutions analyzed, 32 (24%) had evidence of a structured GH program. Of the
      30 (94%) programs for which the authors could find further information online,
      16/30 (53%) were administered by the medical school, whereas 13/30 (43%) were
      administered by a different entity within the university; 1/30 (3%) was jointly
      administered. All 30 of the programs required additional didactic course work.
      The median number of courses was 4 (range: 1-12). Of the 30 schools with GH
      programs, 22 (73%) required an international experiential component, but only
      12/30 (40%) specifically required an international clinical experience. Only 1
      school (3%) directly addressed language or cultural proficiency. CONCLUSIONS:
      Although structured GH programs were offered at one-quarter of U.S. medical
      schools, little standardization across programs existed in terms of requirements
      for didactic, clinical, scholarly, and cultural components. Online GH program
      information is not easily accessible, but it may be valuable in the development
      of new structured programs, the refinement of programs that already exist, and
      students' selection of medical schools.

PMID- 23165272
TI  - The minority student voice at one medical school:  lessons for all?
AB  - PURPOSE: Although the minority population of the United States is projected to
      increase, the number of minority students in medical schools remains stagnant.
      The University of Chicago Pritzker School of Medicine (PSOM) matriculates
      students underrepresented in medicine (URM) above the national average. To
      identify potential strategies through which medical schools can support the
      success of URM medical students, interviews with URM students/graduates were
      conducted. METHOD: Students/recent graduates (within six years) who participated
      in this study self-identified as URMs in medicine and were selected for
      participation using random quota sampling. Participants completed a
      semistructured, qualitative interview in 2009-2010 about their experiences at
      PSOM. Key themes were identified and independently analyzed by investigators to
      ensure intercoder agreement. RESULTS: Participants identified five facets of
      their medical school experiences that either facilitated or hindered their
      academic success. Facilitators of support clustered in three categories: the
      collaborative learning climate at PSOM, the required health care disparities
      course, and student body diversity. Inhibitors of support clustered in two
      categories: insufficiently diverse faculty; and expectations-from self and others
      to fulfill additional responsibilities, or carry a disproportionate burden.
      CONCLUSIONS: Intentional cultivation of a collaborative learning climate, formal
      inclusion of health care disparities curriculum, and commitment to fostering
      student body diversity are three routes by which PSOM has supported URM students.
      Additionally, recognizing the importance of building a diverse faculty and
      extending efforts to decrease the disproportionate burden and stereotype threat
      felt by URM students are institutional imperatives.

PMID- 23165273
TI  - How do gender and anxiety affect students' self-assessment and actual performance
      on a high-stakes clinical skills examination?
AB  - PURPOSE: Research suggests that medical students are not accurate in self
      assessment, but it is not clear whether students over- or underestimate their
      skills or how certain characteristics correlate with accuracy in self-assessment.
      The goal of this study was to determine the effect of gender and anxiety on
      accuracy of students' self-assessment and on actual performance in the context of
      a high-stakes assessment. METHOD: Prior to their fourth year of medical school,
      two classes of medical students at Johns Hopkins University School of Medicine
      completed a required clinical skills exam in fall 2010 and 2011, respectively.
      Two hundred two students rated their anxiety in anticipation of the exam and
      predicted their overall scores in the history taking and physical examination
      performance domains. A self-assessment deviation score was calculated by
      subtracting each student's predicted score from his or her score as rated by
      standardized patients. RESULTS: When students self-assessed their data gathering
      performance, there was a weak negative correlation between their predicted scores
      and their actual scores on the examination. Additionally, there was an
      interaction effect of anxiety and gender on both self-assessment deviation scores
      and actual performance. Specifically, females with high anxiety were more
      accurate in self-assessment and achieved higher actual scores compared with males
      with high anxiety. No differences by gender emerged for students with moderate or
      low anxiety. CONCLUSIONS: Educators should take into account not only gender but
      also the role of emotion, in this case anxiety, when planning interventions to
      help improve accuracy of students' self-assessment.

PMID- 23165274
TI  - Competency-based curricula to transform global health:  redesign with the end in
      mind.
AB  - PURPOSE: To define the education and training priorities for a new 21st-century,
      competency-based, global health curriculum for the University of Washington's
      Department of Global Health (DGH). METHOD: In 2008 and 2009, the authors
      conducted 26 in-depth interviews with global health leaders. They asked
      interviewees to envision key roles and competencies for global health
      professionals at least 20 years from now. The authors also explored training
      approaches and recruitment priorities with the interviewees. The majority of
      interviews were conducted by telephone and audio-recorded. Transcriptions were
      analyzed and coded to identify themes. RESULTS: Interviewees viewed determinants
      of health and systems thinking as two essential areas of knowledge; they
      identified analytical, leadership and management, and policy-development skills
      as priority skill sets. Participants emphasized that training should focus on
      experiential learning, on interdisciplinary and interprofessional collaboration,
      and on information analysis and synthesis. CONCLUSIONS: The University of
      Washington's DGH is currently revising its curriculum across programs and mapping
      it to interrelated competencies: (1) knowledge of social, economic, and
      environmental determinants of health, (2) knowledge of the architecture and
      levers of health, health-relevant systems, and health service delivery, (3)
      skills in epidemiology and in monitoring and evaluation, (4) capacity to manage
      and lead, and (5) skills in policy analysis and development. The curriculum,
      which provides evidence-based education and training in these areas, is designed
      with the end-global health competency in the 21st century-in mind.

PMID- 23165275
TI  - Outcomes of different clerkship models:  longitudinal integrated, hybrid, and
      block.
AB  - PURPOSE: To examine student perceptions and learning outcomes of three different
      third-year clerkship models: a yearlong, longitudinal, integrated clerkship
      (LIC); six-month clerkships with continuity (hybrid); and traditional, discipline
      specific block clerkships (BCs). METHOD: The authors compared the perceptions
      regarding the clerkship year and the hidden curriculum, as well as the pre- and
      postclerkship academic performance, of third-year medical students participating
      in LIC, hybrid, and BC models between 2006 and 2010. RESULTS: Generally, LIC
      students rated the following clerkship experiences higher than did the hybrid and
      BC students: faculty teaching, faculty observation of clinical skills, feedback,
      and the clerkship overall. Students in the LIC observed more positive role
      modeling behaviors and had more patient-centered experiences than BC students.
      All students preferred to see patients more than once, work within a consistent
      site or system, and work with a stable group of peers and faculty mentors over
      time. Whereas students in both the LIC and the hybrid models outperformed their
      BC counterparts in clinical skills, student performance on the U.S. Medical
      Licensing Exam Step 2 (clinical knowledge) was equivalent across models.
      CONCLUSIONS: Key differences in student experiences and outcomes between the
      continuity clerkship models (LIC and hybrid) and BCs reinforce the literature and
      the educational framework for continuity in clinical learning. The benefits to
      student outcomes seem to increase with greater opportunities for continuity.

PMID- 23165276
TI  - Perspective: A framework for career paths in health systems improvement.
AB  - The difference between the U.S. health care system's potential and the outcomes
      it delivers is vast and well documented. Fortunately, many medical trainees
      recognize this challenge and aspire to careers that will enable them to help
      close this gap by improving the systems of care around them. However, the career
      paths in health systems improvement are not well defined, and interested trainees
      are frequently left without clear direction. The circuitous and often
      serendipitous routes that many current leaders in health systems improvement-
      including medical researchers, health system managers, and policy experts--have
      navigated to reach their positions of influence do not provide consistent road
      maps for the trainees who wish to follow in their footsteps.The authors of this
      Perspective propose a framework to guide career development in health systems
      improvement. The framework is designed to help medical trainees and their mentors
      critically analyze various career options in three core focus areas (research,
      policy, management) and the intersections where those areas overlap (policy
      advising, implementation science, policy translation).The authors provide
      examples of the types of work done in each focus area and each intersection to
      help trainees make explicit decisions concerning skill development and to select
      opportunities that best fit their interests and strengths. In all, the authors
      intend the framework to support the development of a generation of physician
      leaders equipped to drive the improvement that the U.S. heath care system
      requires.

PMID- 23165277
TI  - The attributes of the clinical trainer as a role model:  a systematic review.
AB  - PURPOSE: Medical trainees (interns and residents) and their clinical trainers
      need to be aware of the differences between positive and negative role modeling
      to ensure that trainees imitate and that trainers demonstrate the professional
      behavior required to provide high-quality patient care. The authors
      systematically reviewed the medical and medical education literature to identify
      the attributes characterizing clinical trainers as positive and negative role
      models for trainees. METHOD: The authors searched the MEDLINE, EMBASE, ERIC, and
      PsycINFO databases from their earliest dates until May 2011. They included
      quantitative and qualitative original studies, published in any language, on role
      modeling by clinical trainers for trainees in graduate medical education. They
      assessed the methodological quality of and extracted data from the included
      studies, using predefined forms. RESULTS: Seventeen articles met inclusion
      criteria. The authors divided attributes of role models into three categories:
      patient care qualities, teaching qualities, and personal qualities. Positive role
      models were frequently described as excellent clinicians who were invested in the
      doctor-patient relationship. They inspired and taught trainees while carrying out
      other tasks, were patient, and had integrity. These findings confirm the implicit
      nature of role modeling. Positive role models' appearance and scientific
      achievements were among their least important attributes. Negative role models
      were described as uncaring toward patients, unsupportive of trainees, cynical,
      and impatient. CONCLUSIONS: The identified attributes may help trainees recognize
      which aspects of the clinical trainer's professional behavior to imitate, by
      adding the important step of apperception to the process of learning professional
      competencies through observation.

PMID- 23165278
TI  - Policies, activities, and structures supporting research mentoring:  a national
      survey of academic health centers with clinical and translational science awards.
AB  - PURPOSE: To document the frequency of policies and activities in support of
      mentoring practices at institutions receiving a U.S. National Institutes of
      Health's Clinical and Translational Science Award (CTSA). METHOD: The study
      consisted of a 69-item survey with questions about the inclusion (formal or
      informal) of policies, activities, and structures supporting mentoring within
      CTSA-sponsored research (i.e., KL2 programs) and, more broadly, in the CTSA's
      home institution. The survey, conducted from November 2010 through January 2011,
      was sent to the 55 institutions awarded CTSAs at the time of the survey. Follow
      up phone interviews were conducted to clarify responses as needed. RESULTS: Fifty
      one of 55 (92%) institutions completed the survey for institutional programs and
      53 of 55 (96%) for KL2 programs. Responses regarding policies and activities
      involving mentor criteria, mentor-mentee relationship, incentives, and evaluative
      mechanisms revealed considerable variability between KL2 and institutional
      programs in some areas, such as having mentor qualification criteria and
      processes to evaluate mentors. The survey also identified areas, such as training
      and women and minority mentoring programs, where there was frequent sharing of
      activities between the institutional and KL2 programs. CONCLUSIONS: KL2 programs
      and institutional programs tend to have different preferences for policies versus
      activities to optimize qualification of mentors, the mentor-mentee relationship,
      incentives, and evaluation mechanisms. Frequently, these elements are informal.
      Individuals in charge of implementing and maintaining mentoring initiatives can
      use the results of the study to consider their current mentoring policies,
      structures, and activities by comparing them with national patterns within CTSA
      institutions.

PMID- 23165279
TI  - Can medical students afford to choose primary care? An economic analysis of
      physician education debt repayment.
AB  - PURPOSE: Some discussions of physician specialty choice imply that indebted
      medical students avoid choosing primary care because education debt repayment
      seems economically unfeasible. The authors analyzed whether a physician earning a
      typical primary care salary can repay the current median level of education debt
      and meet standard household expenses without incurring additional debt. METHOD:
      In 2010-2011, the authors used comprehensive financial planning software to model
      the annual finances for a fictional physician's household to compare the impact
      of various debt levels, repayment plans, and living expenses across three
      specialties. To accurately develop this spending model, they used published data
      from federal and local agencies, real estate sources, and national organizations.
      RESULTS: Despite growing debt levels, the authors found that physicians in all
      specialties can repay the current level of education debt without incurring more
      debt. However, some scenarios, typically those with higher borrowing levels,
      required trade-offs and compromises. For example, extended repayment plans
      require large increases in the total amount of interest repaid and the number of
      repayment years required, and the use of a federal loan forgiveness/repayment
      program requires a service obligation such as working at a nonprofit or
      practicing in a medically underserved area. CONCLUSIONS: A primary care career
      remains financially viable for medical school graduates with median levels of
      education debt. Graduates pursuing primary care with higher debt levels need to
      consider additional strategies to support repayment such as extended repayment
      terms, use of a federal loan forgiveness/repayment program, or not living in the
      highest-cost areas.

PMID- 23165280
TI  - Physician shadowing:  a review of the literature and proposal for guidelines.
AB  - PURPOSE: Premedical students commonly shadow physicians to gain an understanding
      of what careers in medicine entail. The authors reviewed the literature to
      explore (1) whether shadowing achieves this goal consistently and effectively,
      (2) the ethical issues involved, and (3) other reasons that individuals shadow
      physicians. METHOD: The authors searched the MEDLINE database via Ovid for
      English-language articles published from 1948 to March 2011. Eligible articles
      described physician shadowing programs and/or assessed the value of physician
      shadowing independently or in comparison with other educational methods. RESULTS:
      Of 770 articles identified, 13 articles about physician shadowing programs met
      inclusion criteria. Two of the 13 programs involved shadowing only, whereas 11
      included other educational initiatives. Participants varied; shadowers included
      students (high school, college, medical school), recent medical school graduates,
      or international medical graduates. Few studies addressed shadowing by premedical
      students. Most studies involved programs outside the United States. Shadowing
      program objectives and characteristics differed. Data reported from focus groups,
      interviews, and surveys suggest that shadowing experiences generally increased
      participants' interest in medicine (or a specialty) or improved participants'
      confidence in transitioning to a new position. Some articles raised ethical and
      practical concerns related to shadowing. CONCLUSIONS: The few shadowing programs
      described in the literature were heterogeneous and often involved other
      activities. Further research is warranted; objective outcomes measures would be
      useful. The authors propose developing guidelines and introducing a code of
      conduct for premedical students, to enhance the consistency of shadowing
      experiences and address ethical and practical considerations.

PMID- 23165281
TI  - Transformative learning in a professional development course aimed at addressing
      disruptive physician behavior:  a composite case study.
AB  - Disruptive physician behavior presents a challenge to the academic medical
      center. Such behaviors threaten the learning environment through increasing staff
      conflict, role modeling poor behaviors to trainees, and, ultimately, posing a
      risk to patient safety. Given that these physicians are often respected and
      valued for their clinical skills, many institutions struggle with how to best
      manage their behaviors. The authors present a composite case study of an academic
      physician referred to a professional development program for his disruptive
      behavior. They outline how transformative learning was applied to the development
      of concrete learning objectives, activities, and assessments for a curriculum
      aimed at promoting behavior change. Important themes include a safe group process
      in which the physician's assumptions are critically examined so that through
      experiential exercises and reflection, new roles, skills, and behaviors are
      learned, explored, and practiced. Timely feedback to the physician from the
      institution, colleagues, and administrators is critical to the physician's
      understanding of the impact of his or her behavior. Ultimately, the physician
      returns to practice demonstrating more professional behavior. Implications for
      medical education, prevention, and other professional development programs are
      discussed.

PMID- 23165283
TI  - Strong optical coupling between mutually orthogonal plasmon oscillations in a
      silver nanosphere-nanowire joined system.
AB  - A top-to-bottom joined system consisting of a silver nanowire and nanospheres was
      fabricated by embedding silver nanospheres on a glass or silicon substrate on
      which 3-aminothiophenol as an analyte molecule was adsorbed, and then placing
      silver nanowires on the substrate to make gap sites between a nanowire and
      nanospheres. In the far-field Raman measurements, the sphere under the wire
      exhibited more than 60 times higher Raman enhancement than isolated spheres. The
      surface enhanced Raman scattering (SERS) spectra obtained by the 647.1 nm
      excitation showed highly polarized feature, exhibiting ca. 4 times higher SERS
      intensity for the electric field parallel to the wire axis than that
      perpendicular to the wire axis while those by the 514.5 nm excitation showed non
      polarized feature against the incident electric field direction. The polarized
      feature by the 647.1 nm excitation is explained in terms of optical coupling in a
      vertical direction to the substrate plane, between the silver nanosphere and the
      longitudinal surface plasmon mode of the nanowire. The longitudinal plasmon of
      the nanowire functions as an antenna of the incident radiation field in this type
      of coupled plasmon mode, to yield the confined field. Near-field two-photon
      excitation imaging measurements as well as numerical calculations of the
      localized electric field around the system support this idea and indicate that
      the coupling between the surface plasmon of silver nanospheres and the
      longitudinal mode of silver nanowires is site-selective.

PMID- 23165284
TI  - Codopant ion-induced tunable upconversion emission in beta-NaYF4:Yb3+/Tm3+
      nanorods.
AB  - An innovative route to tune upconversion (UC) emission in beta
      NaYF(4):Yb(3+)/Tm(3+) nanorods through codoping a third rare-earth ion upon
      continuous wave excitation near 976 nm is reported. The dependence of UC emission
      on codopant concentration and environment temperature shows that tailored local
      environment and readjustable depopulation of excited-state ions are responsible
      for the tuning of UC luminescence. Codopant ions introduce a new distribution of
      active ions and a modified distance between Tm(3+) and Yb(3+) ions, making UC
      systems more sensitive to impurity ions than downconversion systems.

PMID- 23165282
TI  - Fig4 deficiency: a newly emerged lysosomal storage disorder?
AB  - FIG4 (Sac3 in mammals) is a 5'-phosphoinositide phosphatase that coordinates the
      turnover of phosphatidylinositol-3,5-bisphosphate (PI(3,5)P(2)), a very low
      abundance phosphoinositide. Deficiency of FIG4 severely affects the human and
      mouse nervous systems by causing two distinct forms of abnormal lysosomal
      storage. The first form occurs in spinal sensory neurons, where vacuolated
      endolysosomes accumulate in perinuclear regions. A second form occurs in
      cortical/spinal motor neurons and glia, in which enlarged endolysosomes become
      filled with electron dense materials in a manner indistinguishable from other
      lysosomal storage disorders. Humans with a deficiency of FIG4 (known as Charcot
      Marie-Tooth disease type 4J or CMT4J) present with clinical and
      pathophysiological phenotypes indicative of spinal motor neuron degeneration and
      segmental demyelination. These findings reveal a signaling pathway involving FIG4
      that appears to be important for lysosomal function. In this review, we discuss
      the biology of FIG4 and describe how the deficiency of FIG4 results in lysosomal
      phenotypes. We also discuss the implications of FIG4/PI(3,5)P(2) signaling in
      understanding other lysosomal storage diseases, neuropathies, and acquired
      demyelinating diseases.

PMID- 23165285
TI  - TACI mutation p.Lys154Ter identified in Good Syndrome.

PMID- 23165286
TI  - Hepatitis B virus status and the risk of pancreatic cancer: a meta-analysis.
AB  - OBJECTIVE: Whether hepatitis B virus (HBV) infection increases the risk of
      pancreatic cancer (PaC) is controversial. We carried out a meta-analysis to
      evaluate the association between HBV status and the risk of PaC. METHODS: PubMed,
      Embase, and the China National Knowledge Infrastructure were searched from their
      inception through April 2012 for case-control and cohort studies that have
      reported an association between HBV status and the risk of PaC. The reference
      lists of pertinent publications were also reviewed for potential studies.
      Methodological quality was assessed using the Newcastle-Ottawa Quality Assessment
      Scale. A random-effects model was used to summarize odd ratios (ORs) and 95%
      confidence intervals (CIs). RESULTS: We included seven case-control studies and
      three cohort studies, involving 5883 PaC cases. The summary OR of developing PaC
      was 1.22 (95% CI: 0.90-1.67) for individuals who were HBV surface antigen (HBsAg)
      positive. Compared with the individuals who were never exposed to HBV infection,
      the summary OR of the risk of PaC was 1.60 (95% CI: 1.26-2.05) for chronic or
      inactive HBsAg carriers (HBsAg-positive) and 1.76 (95% CI: 1.05-2.93) for anti
      HBc-positive but anti-HBs-negative individuals. CONCLUSION: Inactive HBsAg
      carrier status and possible occult HBV infection may increase the risk of PaC.
      Large population-based multicenter prospective studies are required to further
      confirm this finding.

PMID- 23165287
TI  - The cloning and inducible expression of the rainbow trout ERp57 gene.
AB  - ERp57 is a member of a protein disulfide isomerase family and is a chaperone
      responsible for the correct folding of newly synthesized glycoproteins in the
      endoplasmic reticulum and in the assembly of the major histocompatibility complex
      class I in the endogenous pathway of antigen presentation. This study reports the
      identification of a full length ERp57 cDNA in rainbow trout that encodes a
      putative 477aa mature protein with an additional signal sequence of 16aa. The
      trout protein shared 75% identity with the human homolog, but interestingly did
      not include either a C terminal endoplasmic reticulum retention signal, Q/KEDL in
      humans, or a nuclear localization signal which is highly conserved in mammals.
      Amino acid sequence alignment revealed conservation of four classical domains in
      trout ERp57 and two conserved active CXXC redox motifs. Trout ERp57 protein was
      identified as a single band around 57 kDa. Southern blotting analysis revealed
      that there two copies of the ERp57 gene in the trout genome and northern blotting
      showed a wide tissue distribution of gene expression in various tissues with the
      highest expression in liver and egg. This study showed for the first time in
      teleost that ERp57 transcript is upregulated in response to immune stimuli such
      as double stranded RNA or phytohemagglutinin. Furthermore, upon treatment with ER
      stress inducer A23187, trout ERp57 protein expression levels were increased both
      in peripheral blood leukocytes and the RTS11 macrophage like cell line after 6
      and 8 h respectively. These findings suggest a possible conserved function for
      trout ERp57 in the ER and during the activation of the immune response.

PMID- 23165288
TI  - High ordered biomineralization induced by carbon nanoparticles in the sea urchin
      Paracentrotus lividus.
AB  - A surprising and unexpected biomineralization process was observed  during
      toxicological assessment of carbon nanoparticles on Paracentrotus lividus (sea
      urchin) pluteus larvae. The larvae activate a process of defense against external
      material, by incorporating the nanoparticles into microstructures of aragonite
      similarly to pearl oysters. Aiming at a better understanding of this phenomenon,
      the larvae were exposed to increasing concentrations of carbon nanoparticles and
      the biomineralization products were analyzed by electron microscopy, x-ray
      diffraction and Raman spectroscopy. In order to evaluate the possible influence
      of Sp-CyP-1 expression on this biomineralization process by larvae, analyses of
      gene expression (Sp-CyP-1) and calcein labeling were performed. Overall, we
      report experimental evidence about the capability of carbon nanoparticles to
      induce an increment of Sp-CyP-1 expression with the consequent activation of a
      biomineralization process leading to the production of a new pearl-like
      biomaterial never previously observed in sea urchins.

PMID- 23165289
TI  - Hierarchical TiO2 microspheres comprised of anatase nanospindles for improved
      electron transport in dye-sensitized solar cells.
AB  - Hierarchical TiO(2) microspheres assembled by nanospindles were prepared via a
      two-step hydrothermal method. The as-prepared products have uniform diameters of
      ~450 nm and surface area of ~88 m(2) g(-1). The optical investigation evidenced
      that the photoanode film has a prominent light scattering effect at a wavelength
      range of 600-800 nm and possesses enhanced dye loading capacity. In addition, the
      electron recombination and transport dynamic measurements indicated that these
      hierarchical products could suppress the recombination and improve the diffusion
      coefficient of the photoelectrons, which can be attributed to the improvement of
      the connectivity by bridging the neighbouring microspheres through the embedded
      nanospindles. As a result, a high power conversion efficiency of 8.5% was
      demonstrated, indicating a ~30% improvement compared with the cell derived from
      the well-defined nanocrystalline microspheres (6.5%).

PMID- 23165290
TI  - Amperometric immunobiosensor for alpha-fetoprotein using Au
      nanoparticles/chitosan/TiO(2)-graphene composite based platform.
AB  - A simple label-free amperometric immunosensor for protein detection is developed
      based on TiO(2)-graphene (TiO(2)-Gr), chitosan and gold nanoparticles (AuNPs)
      composite film modified glassy carbon electrode (GCE). The negatively charged
      AuNPs can be adsorbed on the positively charged chitosan/TiO(2)-Gr composite film
      by electrostatic adsorption, and then is used to immobilize alpha-fetoprotein
      antibody for the assay of alpha-fetoprotein (AFP). The interaction of antigen and
      antibody on the electrode interface makes a barrier for electrons and inhibits
      the electro-transfer, resulting in the decreased DPV signals of probe Fe(CN)(6)(3
      /4-). Using this strategy, a wide detection range (0.1-300 ng mL(-1)) with the
      correlation coefficients of 0.992-0.994 for model target AFP is obtained. The
      limit of detection is 0.03 ng mL(-1) at a signal-to-noise ratio of 3. The results
      prove that the sensing strategy possesses sensitivity, selectivity, stability and
      generality, and it may be used to immobilize other biomoleculars to develop
      biosensor for the detection of other antigens or biocompounds.

PMID- 23165291
TI  - Solvent nanostructure, the solvophobic effect and amphiphile self-assembly in
      ionic liquids.
AB  - The ability of ionic liquids (ILs) to support amphiphile self-assembly into a
      range of mesophase structures has been established as a widespread phenomenon.
      From the ILs evaluated as self-assembly media, the vast majority have supported
      some lyotropic liquid crystal phase formation. Many neat ionic liquids have been
      shown to segregate into polar and non-polar domains to form a nanostructured
      liquid. A very strong correlation between the nanostructure of the ionic liquid
      and its characteristics as an amphiphile self-assembly solvent has been found. In
      this review we discuss ionic liquids as amphiphile self-assembly media, and
      identify trends that can be used to distinguish which ionic liquids are likely to
      have good promotion properties as self-assembly media. In particular these trends
      focus on the nanostructure of neat ionic liquids, their solvent cohesive energy
      density, and the related solvophobic effect. We forecast that many more ILs will
      be identified as amphiphile self-assembly solvents in the future.

PMID- 23165292
TI  - Sp1 modifies leg-to-wing transdetermination in Drosophila.
AB  - During Drosophila development, the transcription factor Sp1 is necessary for
      proper leg growth and also to repress wing development. Here we test the role of
      Sp1 during imaginal disc regeneration. Ubiquitous expression of wg induces a
      regeneration blastema in the dorsal aspect of the leg disc. Within this
      outgrowth, the wing selector gene vg is activated in some cells, changing their
      fate to wing identity in a process known as transdetermination. In this report we
      demonstrate that reducing the gene copy number of Sp1 significantly increases
      both the frequency and the area of transdetermination in regenerating leg discs.
      By examining the expression of known Sp1 target genes, we also show that the
      proximo-distal patterning gene dachshund is downregulated dorsally, leading to a
      break in its normal ring-shaped expression pattern. We further report that
      transdetermination, as evidenced by Vg expression, is only observed when there is
      a broken ring of Dachshund expression. Combined, these studies establish a role
      for Sp1 in leg-to-wing transdetermination.

PMID- 23165294
TI  - Whole-organ cell shape analysis reveals the developmental basis of ascidian
      notochord taper.
AB  - Here we use in toto imaging together with computational segmentation and analysis
      methods to quantify the shape of every cell at multiple stages in the development
      of a simple organ: the notochord of the ascidian Ciona savignyi. We find that
      cell shape in the intercalated notochord depends strongly on anterior-posterior
      (AP) position, with cells in the middle of the notochord consistently wider than
      cells at the anterior or posterior. This morphological feature of having a
      tapered notochord is present in many chordates. We find that ascidian notochord
      taper involves three main mechanisms: Planar Cell Polarity (PCP) pathway
      independent sibling cell volume asymmetries that precede notochord cell
      intercalation; the developmental timing of intercalation, which proceeds from the
      anterior and posterior towards the middle; and the differential rates of
      notochord cell narrowing after intercalation. A quantitative model shows how the
      morphology of an entire developing organ can be controlled by this small set of
      cellular mechanisms.

PMID- 23165293
TI  - Evolutionary conservation of Nkx2.5 autoregulation in the second heart field.
AB  - The cardiac homeobox gene Nkx2.5 plays a key and dosage-sensitive role in the
      differentiation of outflow tract and right ventricle from progenitors of the
      second heart field (SHF) and Nkx2.5 mutation is strongly associated with human
      outflow tract congenital heart disease (OFT CHD). Therefore defining the
      regulatory mechanisms controlling Nkx2.5 expression in SHF populations serves an
      important function in understanding the etiology of complex CHD. Through a
      comparative analysis of regulatory elements controlling SHF expression of Nkx2.5
      in the chicken and mouse, we have found evidence that Nkx2.5 autoregulation is
      important for maintaining Nkx2.5 expression during SHF differentiation in both
      species. However the mechanism of Nkx2.5 maintenance differs between placental
      mammals and non-mammalian vertebrates: in chick Nkx2.5 binds directly to a
      genomic enhancer element that is required to maintain Nkx2.5 expression in the
      SHF. In addition, it is likely that this is true in other non-mammalian
      vertebrates given that they possess a similar genomic organization. By contrast,
      in placental mammals, Nkx2.5 autoregulation in the SHF functions indirectly
      through Mef2c. These data underscore a tight relationship in mammals between
      Nkx2.5 and Mef2c in SHF transcriptional regulation, and highlight the potential
      for evolutionary cis-regulatory analysis to identify core, conserved components
      of the gene networks controlling heart development.

PMID- 23165295
TI  - Thyroid hormone and retinoic acid interact to regulate zebrafish craniofacial
      neural crest development.
AB  - Craniofacial and ocular morphogenesis require proper regulation of cranial neural
      crest migration, proliferation, survival and differentiation. Although
      alterations in maternal thyroid hormone (TH) are associated with congenital
      craniofacial anomalies, the role of TH on the neural crest has not been
      previously described. Using zebrafish, we demonstrate that pharmacologic and
      genetic alterations in TH signaling disrupt cranial neural crest migration,
      proliferation, and survival, leading to craniofacial, extraocular muscle, and
      ocular developmental abnormalities. In the rostral cranial neural crest that
      gives rise to the periocular mesenchyme and the frontonasal process, retinoic
      acid (RA) rescued migratory defects induced by decreased TH signaling. In the
      caudal cranial neural crest, TH and RA had reciprocal effects on anterior and
      posterior pharyngeal arch development. The interactions between TH and RA
      signaling were partially mediated by the retinoid X receptor. We conclude that TH
      regulates both rostral and caudal cranial neural crest. Further, coordinated
      interactions of TH and RA are required for proper craniofacial and ocular
      development.

PMID- 23165297
TI  - Chronic kidney disease: The effect of age on CKD outcomes.

PMID- 23165298
TI  - Chronic kidney disease: No significant effect of cinacalcet on cardiovascular
      outcomes in patients undergoing dialysis--EVOLVE results.

PMID- 23165296
TI  - Hyponatraemia: more than just a marker of disease severity?
AB  - Hyponatraemia--the most common serum electrolyte disorder--has also emerged as an
      important marker of the severity and prognosis of important diseases such as
      heart failure and cirrhosis. Acute hyponatraemia can cause severe encephalopathy,
      but the rapid correction of chronic hyponatraemia can also profoundly impair
      brain function and even cause death. With the expanding elderly population and
      the increased prevalence of hyponatraemia in this segment of society, prospective
      studies are needed to examine whether correcting hyponatraemia in the elderly
      will diminish cognitive impairment, improve balance and reduce the incidence of
      falls and fractures. Given that polypharmacy is also common in the elderly
      population, the various medications that may stimulate arginine vasopressin
      release and/or enhance the hormone's action to increase water absorption must
      also be taken into consideration. Whether hyponatraemia in a patient with cancer
      is merely a marker of poor prognosis or whether its presence may alter the
      patient's quality of life remains to be examined. In any case, hyponatraemia can
      no longer be considered as just a biochemical bystander in the ill patient. A
      systematic diagnostic approach is necessary to determine the specific aetiology
      of a patient's hyponatraemia. Therapy must then be dictated not only by
      recognized reversible causes such as advanced hypothyroidism, adrenal
      insufficiency, diuretics or other medicines, but also by whether the
      hyponatraemia occurred acutely or chronically. Information is emerging that the
      vast majority of cases of hyponatraemia are caused by the nonosmotic release of
      arginine vasopressin. Now that vasopressin V2-receptor blockers are available, a
      new era of clinical investigation is necessary to examine whether hyponatraemia
      is just a marker of severe disease or whether correction of hyponatraemia could
      improve a patient's quality of life. Such an approach must involve prospective
      randomized studies in different groups of patients with hyponatraemia, including
      those with advanced heart failure, those with cirrhosis, patients with cancer,
      and the elderly.

PMID- 23165299
TI  - Assessing risk in chronic kidney disease: a methodological review.
AB  - Chronic kidney disease (CKD) is an increasingly common public health issue
      associated with substantial morbidity and mortality. Risk prediction models
      provide a useful clinical and research framework for forecasting the probability
      of adverse events and stratifying patients with CKD according to risk; however,
      accurate absolute risk prediction requires careful model specification. Competing
      events that preclude the event of interest (for example, death in studies of end
      stage renal disease) must be taken into account. Functional forms of predictor
      variables and underlying effect modification must be accurately specified;
      nonlinearity and possible interactions should be evaluated. The potential effect
      of measurement error should also be considered. Misspecification of any of these
      components can dramatically affect absolute risk prediction. Evaluation of
      prognostic models should encompass not only traditional tests of calibration and
      discrimination, such as the Hosmer-Lemeshow test of 'goodness of fit' and the
      area under the receiver operating curve, but also newer metrics, such as risk
      reclassification tables and net reclassification indices. The latter two tests
      are particularly useful when considering the addition of novel predictors to
      established models. Finally, models of absolute risk prediction should be
      internally and externally validated as they typically generalize only to
      populations with similar baseline characteristics and rates of competing events.

PMID- 23165300
TI  - Diabetes: Dual RAAS blocker trial stopped prematurely.

PMID- 23165301
TI  - Heart failure: Drugs outperform ultrafiltration in acute cardiorenal syndrome.

PMID- 23165303
TI  - Resistant hypertension--its identification and epidemiology.
AB  - Resistant hypertension is currently defined as the failure to achieve a goal
      blood pressure <140/90 mmHg in patients who are compliant with maximal tolerated
      doses of a minimum of three antihypertensive drugs, one of which must be a
      diuretic. The increasing prevalence of obesity and hypertension in the general
      population mean that this disorder has gained attention in the past decade. In
      the past 2 years, large-scale population-based studies such as the US National
      Health and Nutrition Examination Survey (NHANES) have specifically examined the
      prevalence and incidence of resistant hypertension, and associated risk factors.
      The findings suggest the prevalence of resistant hypertension is 8-12% of adult
      patients with hypertension (6-9 million people). The increasing prevalence of
      resistant hypertension contrasts with the improvement in blood pressure control
      rates during the same period. Studies also show that patients with resistant
      hypertension aged >55 years, of black ethnicity, with high BMI, diabetes or
      chronic kidney disease have an increased risk of cardiovascular events compared
      to nonresistant hypertensive patients. Analyses that exclude the effects of white
      coat hypertension and pseudoresistant hypertension are also needed to clarify the
      epidemiology of true resistant hypertension.

PMID- 23165302
TI  - Key developments in renin-angiotensin-aldosterone system inhibition.
AB  - The renin-angiotensin-aldosterone system (RAAS) was initially thought to be
      fairly simple. However, this idea has been challenged following the development
      of RAAS blockers, including renin inhibitors, angiotensin-converting-enzyme (ACE)
      inhibitors, type 1 angiotensin II (AT(1))-receptor blockers and mineralocorticoid
      receptor antagonists. Consequently, new RAAS components and pathways that might
      contribute to the effectiveness of these drugs and/or their adverse effects have
      been identified. For example, an increase in renin levels during RAAS blockade
      might result in harmful effects via stimulation of the prorenin receptor (PRR),
      and prorenin-the inactive precursor of renin-might gain enzymatic activity on PRR
      binding. The increase in angiotensin II levels that occurs during AT(1)-receptor
      blockade might result in beneficial effects via stimulation of type 2 angiotensin
      II receptors. Moreover, angiotensin 1-7 levels increase during ACE inhibition and
      AT(1)-receptor blockade, resulting in Mas receptor activation and the induction
      of cardioprotective and renoprotective effects, including stimulation of tissue
      repair by stem cells. Finally, a role of angiotensin II in sodium and potassium
      handling in the distal nephron has been identified. This finding is likely to
      have important implications for understanding the effects of RAAS inhibition on
      whole body sodium and potassium balance.

PMID- 23165305
TI  - Vasculitis: Refining phenotypes in ANCA-associated vasculitis.

PMID- 23165306
TI  - Glomerular disease: Gain-of-glycosylation mutation in ITGA3 causes nephrotic
      syndrome.

PMID- 23165304
TI  - Alport syndrome--insights from basic and clinical research.
AB  - In 1927, Arthur C. Alport first published his description of a triad of symptoms
      in a family with hereditary congenital haemorrhagic nephritis, deafness and
      ocular changes. A few years after his death, this group of symptoms was renamed
      Alport syndrome. To this day, Alport syndrome still inevitably leads to end-stage
      renal disease and the need for renal replacement therapy, starting in young
      adulthood. During the past two decades, research into this rare disease has
      focused on the effects of mutations in collagen type IV and the role of changes
      in podocytes and the glomerular basement membrane that lead to early kidney
      fibrosis. Animal models of Alport syndrome also demonstrate the pathogenetic
      importance of interactions between podocytes and the extracellular matrix. Such
      models might also help researchers to answer basic questions about podocyte
      function and the development of fibrosis, and to develop new therapeutic
      approaches that might be of use in other kidney diseases. In this Review, we
      discuss the latest basic and clinical research on Alport syndrome, focusing on
      the roles of podocyte pathology and the extracellular matrix. We also highlight
      early diagnosis and treatment options for young patients with this disorder.

PMID- 23165308
TI  - Synthesis and antimicrobial activity of some new pyrimidinone and oxazinone
      derivatives fused with thiophene rings using 2-chloro-6-ethoxy-4-acetylpyridine
      as starting material.
AB  - A series of pyridines, pyrimidinones, oxazinones and their derivatives were
      synthesized as antimicrobial agents using citrazinic acid (2,6
      dihydroxyisonicotinic acid) as a starting material. alpha,beta-Unsaturated
      ketones 3a-c were condensed with cyanothio-acetamide in the presence of ammonium
      acetate to give 2-cyanopyridinethiones 4a-c, which were reacted with ethyl
      chloroacetate to yield the corresponding cyano esters 5a-c. The esters 5a-c were
      cyclized by action of sodium methoxide to aminoesters 6a-c, which were aminolyzed
      with ammonia to corresponding aminoamide derivatives 7a-c. Also, the esters 6a-c
      were hydrolyzed with NaOH to the corresponding sodium salt 8a-c, which were
      treated with acetic anhydride to afford 2-methyloxazinones 9a-c. The latter
      compounds were treated with ammonium acetate to afford 2-methylpyrimidinones 10a
      c, followed by methylation with methyl iodide to yield 2,3-dimethyl-pyrimidinones
      11a-c. The antimicrobial screening showed that many of these compounds have good
      antibacterial and antifungal activities comparable to streptomycin and fusidic
      acid used as reference drugs.

PMID- 23165309
TI  - Clerodendranoic acid, a new phenolic acid from Clerodendranthus spicatus.
AB  - Phenolic acid derivatives are typical constituents of Clerodendranthus spicatus
      which were considered to the active principles of this medicinal plant. These
      chemical constituents with their interesting frameworks and biological
      significance attracted our attention. As part of our ongoing chemical
      investigation of C. spicatus using various column chromatography techniques, a
      new phenolic compound, named clerodendranoic acid (1), was isolated from the
      aerial parts of C. spicatus together with five known ones, including rosmarinic
      acid (2), methyl rosmarinate (3), caffeic acid (4), methyl caffeate (5), ethyl
      caffeate (6). Their structures, including stereochemical configurations, were
      completely established by extensive spectroscopic methods, mainly inclvolving 1D,
      2D NMR, as well as HRESIMS.

PMID- 23165311
TI  - Modulation of excimer formation of 9-(dicyano-vinyl)julolidine by the macrocyclic
      hosts.
AB  - This article reports the alteration of the excited state photophysics of a
      molecular rotor, namely 9-(dicyano-vinyl)julolidine (DCVJ), which has been
      extensively used to report protein aggregation and protein conformational
      changes, by the various cavity sizes of cyclodextrin (CD) macrocyclic hosts, with
      the help of steady state, time-resolved fluorescence techniques. It is observed
      that, in the presence of alpha-CD, the characteristic features of both the
      monomer and excimer emissions of DCVJ are almost unperturbed. However, in the
      presence of beta-CD, the excited photophysics of the molecule is significantly
      perturbed, and it is noted that beta-CD inhibits the excimer formation drift of
      DCVJ by incorporation of a DCVJ monomer inside its cavity. The most striking
      findings are observed in the case of gamma-CD. Initially, the excimer peak
      intensity drops and the monomer intensity increases, due to the 1 : 1 DCVJ/gamma
      CD inclusion complex formation. Above a certain concentration, another DCVJ
      molecule is accommodated inside the gamma-CD cavity and forms an excimer, which
      is reflected in the intensification of the excimer peak. At higher gamma-CD
      concentration the fluorescence intensity of the excimer shoots up, due to the
      formation of 2 : 2 host-guest complex, in which an additional gamma-CD molecule
      provides extra stabilization to the excimer. Insight on the molecular picture of
      this host-guest interaction has been provided by docking studies followed by
      quantum chemical calculations.

PMID- 23165310
TI  - The emerging role of Interleukin 27 in inflammatory arthritis and bone
      destruction.
AB  - Although the causes of inflammatory arthritis elude us, aberrant cytokine
      expression has been linked to joint pathology. Consequently, several approaches
      in the clinic and/or in clinical trials are targeting cytokines, e.g. tumor
      necrosis factor (TNF), Interleukin 23 (IL-23) and Interleukin 17 (IL-17), with
      the goal of antagonizing their respective biologic activity through therapeutic
      neutralizing antibodies. Such, cytokine signaling-dependent molecular networks
      orchestrate synovial inflammation on multiple levels including differentiation of
      myeloid cells to osteoclasts, the central cellular players in arthritis
      associated pathologic bone resorption. Hence, understanding of the cellular and
      molecular mechanisms elicited by synovial cytokine networks that dictate
      recruitment, differentiation and activation of osteoclast precursors and
      osteoclasts, respectively, is central to shaping novel therapeutic options for
      inflammatory arthritis patients. In this article we are discussing the complex
      signaling interactions involved in the regulation of inflammatory arthritis and
      it's associated bone loss with a focus on Interleukin 27 (IL-27). The present
      review will discuss the primary bone-degrading cell, the osteoclast, and on how
      IL-27, directly or indirectly, modulates osteoclast activity in autoimmune-driven
      inflammatory joint diseases.

PMID- 23165312
TI  - Computer simulation study of nanoparticle interaction with a lipid membrane under
      mechanical stress.
AB  - Pore formation of lipid bilayers under mechanical stress is critical to
      biological processes. A series of coarse grained molecular dynamics simulations
      of lipid bilayers with carbon nanoparticles different in size have been
      performed. Surface tension was applied to study the disruption of lipid bilayers
      by nanoparticles and the formation of pores inside the bilayers. The presence of
      small nanoparticles enhances the probability of water penetration thus decreasing
      the membrane rupture tension, while big nanoparticles have the opposite effect.
      Nanoparticle volume affects bilayer strength indirectly, and particle surface
      density can complicate the interaction. The structural, dynamic, elastic
      properties and lateral densities of lipid bilayers with nanoparticles under
      mechanical stress were analyzed. The results demonstrate the ability of
      nanoparticles to adjust the structural and dynamic properties of a lipid
      membrane, and to efficiently regulate the pore formation behavior and
      hydrophobicity of membranes.

PMID- 23165313
TI  - Atrioventricular and interventricular delay optimization and response
      quantification in biventricular pacing: arrival of reliable clinical algorithms
      and research protocols, and how to distinguish them from unreliable counterparts.

PMID- 23165314
TI  - The Peru cervical cancer prevention study (PERCAPS): community-based
      participatory research in Manchay, Peru.
AB  - OBJECTIVE: Cervical cancer is a preventable disease which causes significant
      morbidity and mortality, particularly in developing countries. Although
      technology for early detection continues to improve, prevention programs suffer
      from significant barriers. Community-based participatory research is an approach
      to research which focuses on collaboration with the community to surmount these
      barriers. The objective of this study was to evaluate the utility of community
      based participatory research techniques in a mother-child screen/treat and
      vaccinate program for cervical cancer prevention in Manchay, Peru. MATERIALS AND
      METHODS: Human papillomavirus (HPV) self-sampling and cryotherapy were used for
      the screen/treat intervention, and the Gardasil vaccine was used for the vaccine
      intervention. Community health workers from Manchay participated in a 3-day
      educational course, designed by the research team. The community health workers
      then decided how to implement the interventions in their community. The success
      of the program was measured by (1) the ability of the community health workers to
      determine an implementation plan, (2) the successful use of research forms
      provided, (3) participation and retention rates, and (4) satisfaction of the
      participants. RESULTS: (1) The community health workers used a door-to-door
      approach through which participants were successfully registered and both
      interventions were successfully carried out; (2) registration forms, consent
      forms, and result forms were used correctly with minimal error; (3) screen/treat
      intervention: 97% of registered participants gave an HPV sample, 94% of HPV
      positive women were treated, and 90% returned for 6-month follow-up; vaccine
      intervention: 95% of registered girls received the first vaccine, 97% of those
      received the second vaccine, and 93% the third; (4) 96% of participants in the
      screen/treat intervention reported high satisfaction. CONCLUSIONS: Community
      based participatory research techniques successfully helped to implement a
      screen/treat and vaccinate cervical cancer prevention program in Manchay, Peru.
      These techniques may help overcome barriers to large-scale preventive health-care
      interventions.

PMID- 23165315
TI  - Edge-state-dependent tunneling of dipole-exchange spin waves in submicrometer
      magnetic strips with an air gap.
AB  - We have investigated the tunneling of dipole-exchange spin waves across an air
      gap in submicrometer-sized permalloy magnetic strips by means of micromagnetic
      simulations. The magnetizations beside the gap could form three distinct end
      domain states with various strengths of dipolar coupling. Spin-wave tunneling
      through the gap at individual end-domain states is studied. It is found that the
      tunneling behavior is strongly dependent on these domain states. Nonmonotonic
      decay of transmission of spin waves with the increase of the gap width is
      observed. The underlying mechanism for these behaviors is proposed. The tunneling
      characteristics of the dipole-exchange spin waves differ essentially from those
      of the magnetostatic ones reported previously.

PMID- 23165316
TI  - Association of aspirin resistance with increased stroke severity and infarct
      size.
AB  - OBJECTIVE: To investigate the relationship between aspirin resistance and
      clinical and neuroimaging measures of stroke severity in acute stroke patients.
      DESIGN: Prospective single-center survey of acute ischemic stroke patients
      receiving aspirin therapy. SETTING: The Royal Melbourne Hospital, Parkville,
      Victoria, Australia. PATIENTS: Ninety acute stroke patients who previously
      received aspirin therapy were enrolled. MAIN OUTCOME MEASURES: Clinical stroke
      severity was measured using the National Institutes of Health Stroke Scale
      (NIHSS) and stroke infarct size was measured using the Alberta Stroke Program
      Early CT Score (ASPECTS). Aspirin resistance was measured using the VerifyNow
      system. RESULTS: The mean (SD) age was 75 (9.9) years and 64.4% were male. The
      median NIHSS score and ASPECTS were 4 (interquartile range [IQR], 3-10) and 9
      (IQR, 6-10), respectively. Aspirin resistance was detected in 28.9% (95% CI, 0.19
      to 0.38) of all patients. The median aspirin reaction unit (ARU) was 486.0 (IQR,
      432.3-557.0). Every 1-point increase in ARU was associated with a 0.03-point
      increase in NIHSS score (95% CI, 0.01 to 0.04; P<.001) and a 0.02-point decrease
      in ASPECTS (95% CI, -0.03 to -0.01; P<.001). This corresponded to an approximate
      median increase of 1 point in NIHSS score for every 33-point increase in ARU or a
      decrease of 1 point in ASPECTS for every 50-point increase in ARU. CONCLUSIONS:
      Aspirin resistance is associated with increased clinical severity and stroke
      infarct volume in acute stroke patients. Our results support the need for a
      randomized controlled study to investigate alternative antiplatelet therapy in
      patients with aspirin resistance.

PMID- 23165317
TI  - Targeting SHP2 phosphatase in myeloproliferative neoplasms.

PMID- 23165318
TI  - Modified PADSS (Post Anaesthetic Discharge Scoring System) for monitoring
      outpatients discharge.
AB  - The decision to discharge a patient undergoing day surgery is a major step in the
      hospitalization pathway, because it must be achieved without compromising the
      quality of care, thus ensuring the same assistance and wellbeing as for a long
      term stay. Therefore, the use of an objective assessment for the management of a
      fair and safe discharge is essential. The authors propose the Post Anaesthetic
      Discharge Scoring System (PADSS), which considers six criteria: vital signs,
      ambulation, nausea/vomiting, pain, bleeding and voiding. Each criterion is given
      a score ranging from 0 to 2. Only patients who achieve a score of 9 or more are
      considered ready for discharge. Furthermore, PADSS has been modified to ensure a
      higher level of safety, thus the "vital signs" criteria must never score lower
      than 2, and none of the other five criteria must ever be equal to 0, even if the
      total score reaches 9. The effectiveness of PADSS was analyzed on 2432 patients,
      by recording the incidence of postoperative complications and the readmission to
      hospital. So far PADDS has proved to be an efficient system that guarantees safe
      discharge.

PMID- 23165319
TI  - Pretreatment of therapeutic cells with poly(ADP-ribose) polymerase inhibitor
      enhances their efficacy in an in vitro model of cell-based therapy in myocardial
      infarct.
AB  - The potential of cell-based therapies in diseases involving ischemia-reperfusion
      is greatly hampered by the excessive loss of administered cells in the harsh and
      oxidative environment where these cells are supposed to act. Therefore, we
      investigated if inhibition of poly(ADP-ribose) polymerase (PARP) in the
      therapeutically added cells would lead to their increased viability and,
      subsequently, to an enhanced effect in an in vitro simulated ischemia-reperfusion
      (I-R) setting. Ischemic conditions were simulated by oxygen and glucose
      deprivation for 160 min using H9c2 rat cardiomyoblast cells. After 30 min of
      reperfusion, these cells received 4 types of treatments: no added cells (I-R
      model), fluorescently labeled (Vybrant DiD) therapeutic H9c2 cells with vehicle
      (H9c2) or PARP inhibitor (10 uM or 100 uM PJ34) pretreatment. We assessed
      viability (live, apoptotic and necrotic) of both 'postischemic' and therapeutic
      cells with flow cytometric analysis using calcein-AM/ethidium homodimer-2
      fluorescent staining after 24 h of co-culture. Further measurements on necrosis
      and metabolic activity were performed using lactate dehydrogenase (LDH) release
      and resazurin based assays. The percentage of surviving therapeutic cells
      increased significantly with PARP inhibition (untreated, 52.02+/-5.01%; 10 uM
      PJ34, 63.38+/-4.50%; 100 uM PJ34, 64.99+/-3.47%). The percentage of necrotic
      cells decreased in a similar manner (untreated, 37.23+/-4.40%; 10 uM PJ34,
      26.83+/-3.49%; 100 uM PJ34, 24.96+/-2.43%). Notably, the survival of the cells
      that suffered I-R injury was also significantly higher when treated with PARP
      inhibited therapeutic cells (I-R model, 36.44+/-5.05%; H9c2, 42.81+/-5.11%; 10 uM
      PJ34, 52.07+/-5.80%; 100 uM PJ34, 54.95+/-5.55%), while necrosis was inhibited (I
      R model, 43.64+/-4.00%; H9c2, 37.29+/-4.55%; 10 uM PJ34, 30.18+/-4.60%; 100 uM
      PJ34, 25.52+/-3.47%). In subsequent experiments, PARP inhibition decreased LDH
      release of the observed combined cell population and enhanced the metabolic
      activity. Thus, our results suggest that pretreating the therapeutically added
      cells with a PARP inhibitor could be beneficial in the setting of cell-based
      therapies.

PMID- 23165320
TI  - Critical role of aquaporin-3 in epidermal growth factor-induced migration of
      colorectal carcinoma cells and its clinical significance.
AB  - Aquaporins (AQPs) are a family of small, integral membrane proteins that have
      been shown to play an important role in tumor development and metastasis. Several
      studies have demonstrated that expression of AQP3 contributes to the enhanced
      migration of epithelial cells and is related to differentiation, metastasis and
      vascular invasion in lung and gastric cancer. Therefore, we investigated whether
      AQP3 could enhance human colorectal carcinoma cell migration and we examined the
      role of AQP3 in the prognosis of colorectal carcinoma. Our results showed that
      human epidermal growth factor (hEGF) increased the expression of AQP3 and,
      subsequently, the migration ability of human colorectal carcinoma cells HCT116 in
      a dose- and time-dependent manner. The enhanced migration ability of HCT116 cells
      was blocked by the AQP3 inhibitor, CuSO(4). Overexpression of AQP3 induced by
      hEGF was inhibited by a PI3K/AKT inhibitor, LY294002, but the ERK inhibitor U0126
      had a minor effect on the hEGF-induced AQP3 upregulation. Immunohistochemical
      staining of the cancer tissues and corresponding normal tissues showed that AQP3
      expression in cancer tissue was higher compared to that in normal tissue. The
      expression intensity of AQP3 was associated with the differentiation, lymph node
      and distant metastasis of colorectal carcinoma patients. Our results suggest that
      AQP3 overexpression could facilitate colorectal carcinoma cell migration and AQP3
      may be considered a potential indicator and therapeutic target for colon tumor
      metastasis and prognosis.

PMID- 23165321
TI  - Effect of novel antibacterial gallium-carboxymethyl cellulose on Pseudomonas
      aeruginosa.
AB  - Gallium has emerged as a new therapeutic agent due partly to the scarcity in
      development of new antibiotics. In this study, a novel antibacterial gallium
      exchanged carboxymethyl cellulose (Ga-CMC) has been developed and tested for the
      susceptibility on a common bacteria, Pseudomonas aeruginosa. The results show
      that an increase in average molecular weight (MW) from 90 k, 250 k to 700 k of Ga
      CMC caused a decrease in antimicrobial activity against planktonic P. aeruginosa.
      Gallium loading of the Ga-CMC (250 k) samples was altered by varying the amount
      of functionality (0.7, 0.9 and 1.2 acid groups per mole of carbohydrate) which
      affected also its antimicrobial activity against planktonic P. aeruginosa.
      Further, the ability to prevent the growth of biofilms of P. aeruginosa was
      tested on MW = 250 k samples with 0.9 acid groups per mole of carbohydrate as
      this sample showed the most promising activity against planktonic P. aeruginosa.
      Gallium was found to reduce biofilm growth of P. aeruginosa with a maximum effect
      (0.85 log(10) CFU reduction compared to sodium-carboxymethyl cellulose, Na-CMC)
      after 24 h. Results of the solubility and ion exchange studies show that this
      compound is suitable for the controlled release of Ga(3+) upon their breakdown in
      the presence of bacteria. SEM EDX analysis confirmed that Ga(3+) ions are evenly
      exchanged on the cellulose surface and systematic controls were carried out to
      ensure that antibacterial activity is solely due to the presence of gallium as
      samples intrinsic acidity or nature of counterion did not affect the activity.
      The results presented here highlight that Ga-CMC may be useful in controlled drug
      delivery applications, to deliver gallium ions in order to prevent infections due
      to P. aeruginosa biofilms.

PMID- 23165322
TI  - Prior knowledge on cortex organization in the reconstruction of source current
      densities from EEG.
AB  - The reconstruction of the generators of electroencephalographic (EEG) signals is
      important for understanding brain processes. Since the inverse problem has no
      unique solution, additional knowledge or assumptions are needed. Often, results
      from other anatomical or functional measurement modalities are difficult to
      interpret directly in terms of EEG source strengths, but they provide valuable
      information about the functional similarity between brain regions, for example,
      in form of parcellations. We propose a novel approach to the incorporation of
      such parcellations as priors into the reconstruction of distributed source
      current densities from EEG. Two algorithms are described, based on a surface
      constrained LORETA (Low Resolution Electromagnetic TomogrAphy) approach. The
      first, patchLORETA1, uses both topological neighborhood and prior information to
      define smoothness, while the second, patchLORETA2, neglects topological
      neighborhood. Computer simulations, using a smooth reconstruction surface on the
      brain envelope, reveal important aspects of the algorithms' performance, in
      particular the influences of noise and incongruence between measurements and
      prior information. It turns out that patchLORETA1 makes efficient use of the
      provided prior information and at the same time is quite robust towards faulty
      priors as well as noise. The algorithms are also tested on the localization of
      the sources of event-related potentials. Here, both the smooth brain and folded
      cortical surfaces serve as reconstruction spaces. We find that patchLORETA1
      becomes ineffective on the folded cortex, while patchLORETA2 yields plausible
      results. We also discuss the extension of the proposed algorithms to other types
      of priors and propose ways to overcome shortcomings of the current
      implementation.

PMID- 23165323
TI  - Using variance information in magnetoencephalography measures of functional
      connectivity.
AB  - The use of magnetoencephalography (MEG) to assess long range functional
      connectivity across large scale distributed brain networks is gaining popularity.
      Recent work has shown that electrodynamic networks can be assessed using both
      seed based correlation or independent component analysis (ICA) applied to MEG
      data and further that such metrics agree with fMRI studies. To date, techniques
      for MEG connectivity assessment have typically used a variance normalised
      approach, either through the use of Pearson correlation coefficients or via
      variance normalisation of envelope timecourses prior to ICA. Here, we show that
      the use of variance information (i.e. data that have not been variance
      normalised) in source space projected Hilbert envelope time series yields
      important spatial information, and is of significant functional relevance.
      Further, we show that employing this information in functional connectivity
      analyses improves the spatial delineation of network nodes using both seed based
      and ICA approaches. The use of variance is particularly important in MEG since
      the non-independence of source space voxels (brought about by the ill-posed MEG
      inverse problem) means that spurious signals can exist in areas of low signal
      variance. We therefore suggest that this approach be incorporated into future
      studies.

PMID- 23165324
TI  - A robust variational approach for simultaneous smoothing and estimation of DTI.
AB  - Estimating diffusion tensors is an essential step in many applications - such as
      diffusion tensor image (DTI) registration, segmentation and fiber tractography.
      Most of the methods proposed in the literature for this task are not
      simultaneously statistically robust and feature preserving techniques. In this
      paper, we propose a novel and robust variational framework for simultaneous
      smoothing and estimation of diffusion tensors from diffusion MRI. Our variational
      principle makes use of a recently introduced total Kullback-Leibler (tKL)
      divergence for DTI regularization. tKL is a statistically robust dissimilarity
      measure for diffusion tensors, and regularization by using tKL ensures the
      symmetric positive definiteness of tensors automatically. Further, the
      regularization is weighted by a non-local factor adapted from the conventional
      non-local means filters. Finally, for the data fidelity, we use the nonlinear
      least-squares term derived from the Stejskal-Tanner model. We present
      experimental results depicting the positive performance of our method in
      comparison to competing methods on synthetic and real data examples.

PMID- 23165326
TI  - Native amorphous nanoheterogeneity in gallium germanosilicates as a tool for
      driving Ga2O3 nanocrystal formation in glass for optical devices.
AB  - Nanoparticles in amorphous oxides are a powerful tool for embedding a wide range
      of functions in optical glasses, which are still the best solutions in several
      applications in the ever growing field of photonics. However, the control of the
      nanoparticle size inside the host material is often a challenging task, even more
      challenging when detrimental effects on light transmittance have to be avoided.
      Here we show how the process of phase separation and subsequent
      nanocrystallization of a Ga-oxide phase can be controlled in germanosilicates -
      prototypal systems in optical telecommunications - starting from a Ga-modified
      glass composition designed to favour uniform liquid-liquid phase separation in
      the melt. Small angle neutron scattering data demonstrate that nanosized
      structuring occurs in the amorphous as-quenched glass and gives rise to initially
      smaller nanoparticles, by heating, as in a secondary phase separation. By further
      heating, the nanophase evolves with an increase of nanoparticle gyration radius,
      from a few nm to a saturation value of about 10 nm, through an initial growing
      process followed by an Ostwald ripening mechanism. Nanoparticles finally
      crystallize, as indicated by transmission electron microscopy and X-ray
      diffraction, as gamma-Ga(2)O(3)- a metastable gallium oxide polymorph. Infrared
      reflectance and photoluminescence, together with the optical absorption of Ni
      ions used as a probe, give an indication of the underlying interrelated processes
      of the structural change in the glass and in the segregated phase. As a result,
      our data give for the first time a rationale for designing Ga-modified
      germanosilicates at the nanoscale, with the perspective of a detailed
      nanostructuring control.

PMID- 23165327
TI  - Patient optimization for gastrointestinal cancer surgery.
AB  - BACKGROUND: Although surgical resection remains the central element in curative
      treatment of gastrointestinal cancer, increasing emphasis and resource has been
      focused on neoadjuvant or adjuvant therapy. Developments in these modalities have
      improved outcomes, but far less attention has been paid to improving oncological
      outcomes through optimization of perioperative care. METHODS: A narrative review
      is presented based on available and updated literature in English and the
      authors' experience with enhanced recovery research. RESULTS: A range of
      perioperative factors (such as lifestyle, co-morbidity, anaemia, sarcopenia,
      medications, regional analgesia and minimal access surgery) are modifiable, and
      can be optimized to reduce short- and long-term morbidity and mortality, improve
      functional capacity and quality of life, and possibly improve oncological
      outcome. The effect on cancer-free and overall survival may be of equal magnitude
      to that achieved by many adjuvant oncological regimens. Modulation of core
      factors, such as nutritional status, systemic inflammation, and surgical and
      disease-mediated stress, probably influences the host's immune surveillance and
      defence status both directly and through reduced postoperative morbidity.
      CONCLUSION: A wider view on long-term effects of expanded or targeted enhanced
      recovery protocols is warranted.

PMID- 23165325
TI  - The triterpenoid cucurbitacin B augments the antiproliferative activity of
      chemotherapy in human breast cancer.
AB  - Despite recent advances in therapy, breast cancer remains the second most common
      cause of death from malignancy in women. Chemotherapy plays a major role in
      breast cancer management, and combining chemotherapeutic agents with
      nonchemotherapeutic agents is of considerable clinical interest. Cucurbitacins
      are triterpenes compounds found in plants of the Cucurbitaceae family, reported
      to have anticancer and anti-inflammatory activities. Previously, we have shown
      antiproliferative activity of cucurbitacin B (CuB) in breast cancer, and we
      hypothesized that combining CuB with chemotherapeutic agents can augment their
      antitumor effect. Here, we show that a combination of CuB with either docetaxel
      (DOC) or gemcitabine (GEM) synergistically inhibited the proliferation of MDA-MB
      231 breast cancer cells in vitro. This antiproliferative effect was accompanied
      by an increase in apoptosis rates. Furthermore, in vivo treatment of human breast
      cancer orthotopic xenografts in immunodeficient mice with CuB at either low (0.5
      mg/kg) or high (1 mg/kg) doses in combination with either DOC (20 mg/kg) or GEM
      (12.5mg/kg) significantly reduced tumor volume as compared with monotherapy of
      each drug. Importantly, no significant toxicity was noted with low-dose CuB in
      combination with either DOC or GEM. In conclusion, combination of CuB at a
      relatively low concentration with either of the chemotherapeutic agents, DOC or
      GEM, shows prominent antiproliferative activity against breast cancer cells
      without increased toxicity. This promising combination should be examined in
      therapeutic trials of breast cancer.

PMID- 23165328
TI  - Advances in analytical methods to study cholesterol metabolism: the determination
      of serum noncholesterol sterols.
AB  - Cholesterol biosynthesis precursors and plant sterols are noncholesterol sterols
      currently used as relative surrogate markers of cholesterol synthesis and
      absorption, respectively. Its determination in serum samples is a way of
      diagnosing inherited disorders and also a tool for health evaluation during lipid
      lowering lifestyle/drug therapy monitoring. This approach is the only one that
      can be used for large-scale clinical trials or population based studies, but,
      nevertheless, there is no reference method for the quantification of
      noncholesterol sterols in human serum samples and only analysis by GC-FID and GC
      MS has been reported to be completely validated. Although there has been a wider
      use of noncholesterol sterols for the measurement and characterization of
      cholesterol metabolism, there is a lack of harmonization of measurements and of
      standardization of the methodology, which is essential for routine measurements
      of diagnostic utility. New recent advances in analytical methods for the
      determination of serum noncholesterol sterols are highlighted, focusing on the
      sample preparation, separation and detection techniques, which will enhance the
      range of applications in clinical practice.

PMID- 23165329
TI  - Dosing of antibiotics in critically ill patients: are we left to wander in the
      dark?
AB  - Critically ill patients are frequently affected by acute kidney injury
      accompanied by dysfunction of other systems and organs. Sepsis is common in this
      population and remains a major cause of multiorgan dysfunction syndrome,
      indicating a crucial role in efficient antibiotic treatment. However, such
      treatment is particularly difficult due to altered pharmacokinetic profile in
      these patients, dynamic changes in their clinical status and, in many cases, need
      for renal replacement therapy (RRT). Current guidelines concerning the dosing of
      antibiotics in this patient population are not particularly reliable because they
      are based on studies involving small and heterogeneous groups of patients, often
      treated with different RRT modalities. Our paper reviews the basic
      pharmacokinetic and pharmacodynamic parameters as well as other factors that
      should be considered while devising a proper therapeutic approach for this
      patient population.

PMID- 23165330
TI  - Asteroid bodies in soft-tissue amyloidoma.

PMID- 23165331
TI  - Study of EWS/FLI-1 rearrangement in 18 cases of CK20+/CM2B4+ Merkel cell
      carcinoma using FISH and correlation to the differential diagnosis of Ewing
      sarcoma/peripheral neuroectodermal tumor.
AB  - Merkel cell carcinoma (MCC) and primary cutaneous Ewing sarcoma/primitive
      neuroectodermal tumors (PCES/PNET) pose a challenging morphologic differential
      diagnosis. Approximately 90% of Ewing sarcoma/primitive neuroectodermal tumors
      (PNETs) have a specific translocation, t(11;22) (q24;q12). The EWS-friend
      leukemia integration-1 (FLI-1) fusion results in FLI-1 overexpression. EWS/FLI-1
      rearrangement has been suggested as a useful tool in the diagnosis of PCES/PNET.
      In contrast, Merkel cell polyomavirus was found to be an infective agent related
      to the pathogenesis of MCC. Merkel cell polyomavirus can be immunohistochemically
      detected with the antibody CM2B4. To the best of our knowledge, there is no case
      of any cytokeratin (CK)20-/CM2B4+ PNET. The goal of our study was to investigate
      whether EWS/FLI-1 rearrangement was present in cases of MCC. We have studied 18
      cases of MCC. To make sure that the cases investigated by fluorescent in situ
      hybridization were genuine MCC, we considered only CK20+/CM2B4+ cases. Six cases
      met this criterion. EWS/FLI-1 rearrangement was not evidenced in any of the 18
      cases (including the 6 "genuine" cases of MCC). Although our findings were
      somewhat expected, we think that they fill a gap in the literature: the
      confirmation that MCC is devoid of the EWS/FLI-1 rearrangement.

PMID- 23165332
TI  - Morphologic features do not influence response to trastuzumab-containing
      neoadjuvant chemotherapy in HER2-positive breast cancer.
AB  - Trastuzumab-containing neoadjuvant chemotherapy in patients with HER2-positive
      breast cancer is highly effective in reducing tumor volume and enables more
      patients to have breast-conserving surgery. The tumor hormone receptor level has
      been shown to significantly influence response to trastuzumab-containing
      neoadjuvant chemotherapy. In this study, we comprehensively evaluated various
      morphologic features and proliferative activity in 50 HER2-positive invasive
      breast carcinomas treated with trastuzumab-containing neoadjuvant chemotherapy to
      determine whether any of these features have the same predictive value as tumor
      hormone receptor content. The tumor proliferation activity as measured by Ki-67
      and various morphologic parameters were compared between tumors that achieved
      >50% tumor volume reduction including pathologic complete response (pCR) and
      tumors that showed <=50% tumor volume reduction. Thirty-seven cases (74%) showed
      >50% tumor volume reduction including 18 cases with pCR. Thirteen cases (26%)
      showed <=50% tumor volume reduction. Neither morphologic variables nor Ki-67
      labeling index were predictive of >50% tumor volume reduction. In contrast,
      hormone receptor status and semiquantitative H scores for hormone receptors were
      predictive of>50% tumor volume reduction. The mean estrogen and progesterone
      receptor H scores for tumors that showed >50% tumor volume reduction (including
      pCR) were 77 (median 10) and 31 (median 0), respectively, compared with 168
      (median 200) and 79 (median 75) for cases that showed <=50% tumor volume
      reduction. Semiquantitative scoring for hormone receptors provides useful
      information in terms of therapeutic response in HER2-positive tumors. 

PMID- 23165333
TI  - Evaluation of SF-1 expression in testicular germ cell tumors: a tissue microarray
      study of 127 cases.
AB  - Differentiating testicular germ cell tumors from sex-cord stromal tumors can be
      difficult in certain cases because of overlapping morphologic features and/or an
      absence of clinically apparent hormonal symptoms. Immunohistochemistry may be
      needed as an ancillary diagnostic tool in this differential diagnostic setting.
      Steroidogenic factor-1 (SF-1) is a nuclear transcription factor controlling
      steroidogenesis and is expressed in developing Sertoli and Leydig cells. Although
      1 recent study has reported SF-1 nuclear immunoreactivity in testicular sex-cord
      stromal tumors, the specificity for this marker in germ cell tumors has not been
      evaluated. After encountering several problematic cases (including some on
      testicular biopsy), we sought to determine the diagnostic specificity of SF-1 in
      a large series of germ cell tumors. Nuclear immunohistochemical expression of SF
      1 was evaluated in 127 germ cell tumors using tissue microarray technology with
      23 non-germ cell tumor tissues as positive internal controls. No nuclear SF-1
      expression was identified in any of the 127 germ cell tumors [including
      choriocarcinoma (3), embryonal carcinoma (25), epidermal inclusion cyst (1),
      intratubular germ cell neoplasia unclassified (4), seminoma (72), spermatocytic
      seminoma (2), teratoma (8), and yolk sac tumor (12)]. All 23 non-germ cell tumor
      tissues showed strong nuclear SF-1 expression in Sertoli and/or Leydig cells
      [including testicular atrophy (10), cryptorchidism (2), normal testis (4),
      hypospermatogenesis (1), immature testis (1), intratubular large cell calcifying
      Sertoli cell tumor (1), Leydig cell tumor (3), and Sertoli only (1)]. This study
      documents the absence of SF-1 expression in testicular germ cell tumors and
      supports its specificity for sex-cord stromal lesions in this diagnostic context.

PMID- 23165334
TI  - The correlations of LMX1A and osteopontin expression to the clinicopathologic
      stages in pancreatic adenocarcinoma.
AB  - AIM: To test the association of LMX1A and osteopontin (OPN) expression with
      histologic differentiation or pathologic stage in pancreatic ductal
      adenocarcinoma. METHODS: Immunohistochemical analysis was performed to determine
      LMX1A and OPN expression in 100 surgical specimens obtained from Chinese patients
      with well-differentiated (n=15), moderately differentiated (n=65), and poorly
      differentiated (n=20) pancreatic ductal adenocarcinomas. RESULTS: LMX1A and OPN
      immunoreactivities were undetectable in normal pancreatic glandular epithelia.
      Stronger immunostaining for LMX1A and OPN was associated with advanced nuclear
      grades of pancreatic ductal adenocarcinomas (70.7 and 87.1 for grade I, 109.8 and
      118.3 for grade II, and 171.3 and 183.8 for grade III), and advanced TNM and
      American Joint Committee on Cancer stages of pancreatic ductal adenocarcinomas.
      CONCLUSIONS: A higher expression of LMX1A and OPN is well correlated with
      histologic grade and pathologic stage of pancreatic ductal adenocarcinomas.

PMID- 23165336
TI  - Alzheimer disease: New insights into preclinical Alzheimer disease.

PMID- 23165335
TI  - Patellar maltracking is prevalent among patellofemoral pain subjects with patella
      alta: an upright, weightbearing MRI study.
AB  - The purpose of this study is to determine if patellar maltracking is more
      prevalent among patellofemoral (PF) pain subjects with patella alta compared to
      subjects with normal patella height. We imaged 37 PF pain and 15 pain free
      subjects in an open-configuration magnetic resonance imaging scanner while they
      stood in a weightbearing posture. We measured patella height using the Caton
      Deschamps, Blackburne-Peel, Insall-Salvati, Modified Insall-Salvati, and
      Patellotrochlear indices, and classified the subjects into patella alta and
      normal patella height groups. We measured patella tilt and bisect offset from
      oblique-axial plane images, and classified the subjects into maltracking and
      normal tracking groups. Patellar maltracking was more prevalent among PF pain
      subjects with patella alta compared to PF pain subjects with normal patella
      height (two-tailed Fisher's exact test, p<0.050). Using the Caton-Deschamps
      index, 67% (8/12) of PF pain subjects with patella alta were maltrackers, whereas
      only 16% (4/25) of PF pain subjects with normal patella height were maltrackers.
      Patellofemoral pain subjects classified as maltrackers displayed a greater
      patella height compared to the pain free and PF pain subjects classified as
      normal trackers (two-tailed unpaired t-tests with Bonferroni correction,
      p<0.017). This study adds to our understanding of PF pain in two ways-(1) we
      demonstrate that patellar maltracking is more prevalent in PF pain subjects with
      patella alta compared to subjects with normal patella height; and (2) we show
      greater patella height in PF pain subjects compared to pain free subjects using
      four indices commonly used in clinics.

PMID- 23165337
TI  - Epigenetic changes in patients with multiple sclerosis.
AB  - Epigenetic changes influence gene expression without altering the DNA sequence.
      DNA methylation, histone modification and microRNA-associated post
      transcriptional gene silencing are three key epigenetic mechanisms. Multiple
      sclerosis (MS) is a disease of the CNS with both inflammatory and
      neurodegenerative features. Although studies on epigenetic changes in MS only
      began in the past decade, a growing body of literature suggests that epigenetic
      changes may be involved in the development of MS, possibly by mediating the
      effects of environmental risk factors, such as smoking, vitamin D deficiency and
      Epstein-Barr virus infection. Such studies are also beginning to deliver
      important insights into the pathophysiology of MS. For example, inflammation and
      demyelination in relapsing-remitting MS may be related to the increased
      differentiation of T cells toward a T-helper 17 phenotype, which is an important
      epigenetically regulated pathophysiological mechanism. In progressive MS, other
      epigenetically regulated mechanisms, such as increased histone acetylation and
      citrullination of myelin basic protein, might exacerbate the disease course. In
      this Review, we summarize current knowledge on the role of epigenetic changes in
      the pathophysiology of MS.

PMID- 23165339
TI  - Genetics: expanding the spectrum of neurological disorders associated with PRRT2
      mutations.

PMID- 23165338
TI  - High-pressure headaches: idiopathic intracranial hypertension and its mimics.
AB  - Idiopathic intracranial hypertension (IIH) is a rare disorder that typically
      affects obese women of childbearing age, but can also occur in paediatric
      populations. Patients usually present with diffuse, daily headache and visual
      disturbances, but either symptom can occur in isolation. Patients with IIH often
      have papilloedema; however, IIH without papilloedema is fairly common in patients
      with chronic daily headache. The pathogenesis of IIH is unknown; the high
      incidence of comorbid bilateral transverse sinus stenosis (BTSS) in patients with
      IIH suggests that the two conditions are linked, although no direct causal
      relationship has been established. Cerebrospinal fluid (CSF) pressure monitoring
      or lumbar puncture-which provides immediate symptomatic relief-are important in
      making a diagnosis of IIH. Current treatments for IIH include weight reduction,
      medical treatment, CSF diversion surgery, optic nerve sheath fenestration and,
      potentially, endovascular stenting (in patients with BTSS). Prevention of visual
      loss (which can be substantial) is the main goal of treatment. Residual headache
      and IIH recurrence are not uncommon after treatment, and regular follow-up is,
      therefore, warranted even in patients who achieve remission. This Review provides
      an update of current knowledge of the aetiology, pathophysiology and treatment of
      IIH.

PMID- 23165341
TI  - Lab-on-graphene: graphene oxide as a triple-channel sensing device for protein
      discrimination.
AB  - The fluorescence, catalytic activity and assembly behavior of GO could be
      simultaneously changed after interaction with proteins, leading to distinct
      response patterns related to each specific protein. Based on the phenomenon, a
      triple-channel optical sensor has been proposed in the present communication for
      protein discrimination with GO as a single sensing element.

PMID- 23165342
TI  - The formation of overlooked compounds in the reaction of methyl amine with the
      diethyl ester of o-phenylenebis(oxamic acid) in MeOH.
AB  - The treatment of the diethyl ester of o-phenylenebis(oxamic acid) (opbaH(2)Et(2))
      with 2/3 of an equivalent of MeNH(2) in MeOH does not result in the formation of
      the methyl ester of o-phenylene(N'-methyloxamide)(oxamic acid) (opooH(3)Me, 1) in
      pure state, as reported previously. The colourless crude material formed by this
      reaction was confirmed to be composed of 1 (89% content), the dimethyl ester of o
      phenylenebis(oxamic acid) (opbaH(2)Me(2), 2, 6%), 1,4-dihydro-2,3
      quinoxalinedione (3, 3%) and o-phenylenebis(N'-methyloxamide) (opboH(4)Me(2), 4,
      1%), respectively. The identities of 1-4 have been verified by IR, (1)H and (13)C
      NMR spectroscopy as well as elemental analysis. In addition, the solid state
      structures of 1 and 2.2DMSO, respectively, were determined by single-crystal X
      ray diffraction studies. Successive recrystallization of the crude material from
      MeOH and MeOH : THF (1 : 1), respectively, does not give pure 1, but a mixture of
      1 and 2. It is shown further that out of this mixture pure bis(oxamato) complexes
      cannot be obtained, as previously reported. Instead, treatment of the mixture
      with Ni(II) or Cu(II) salts, followed by the addition of [(n)Bu(4)N]OH, results
      in the formation of two mixtures of [(n)Bu(4)N](2)[Ni(opba)] (5) and
      [(n)Bu(4)N](2)[Ni(opooMe)] (6) as well as [(n)Bu(4)N](2)[Cu(opba)] (7) and
      [(n)Bu(4)N](2)[Cu(opooMe)] (8), respectively. The simultaneous formation of 5/6
      and 7/8, respectively, has been verified by crystallization of the obtained
      mixtures and X-ray diffraction studies of the obtained single crystals. Co
      crystallization of mixtures of 5/6 (99 mass%) and 7/8 (1 mass%), respectively,
      results in the formation of single-crystals of diamagnetically diluted 7 in the
      host lattice of 5 (7@5) accompanied by single-crystal formation of
      diamagnetically diluted 8 in the host lattice of 6 (8@6), as verified by EPR
      spectroscopy. It is finally shown that the ethyl ester of o-phenylene(N'
      methyloxamide)(oxamic acid) (opooH(3)Et, 9), a homologue of 1, can be obtained in
      pure state by the treatment of opbaH(2)Et(2) with 5/6 of an equivalent of MeNH(2)
      in EtOH.

PMID- 23165343
TI  - Effects of falls experience on cognitive functions and physical activities in
      community-dwelling individuals with chronic stroke.
AB  - The purpose of this study was to examine the effects of falls experience on
      cognitive functions and physical activities in community-dwelling patients with
      chronic hemiparetic stroke. Further, the feasibility of using the Montreal
      Cognitive Assessment (MoCA) to predict falls in the patients was evaluated. Forty
      seven patients with chronic stroke participated in this study. The participants
      included 25 patients with falls experience (faller group) and 22 patients without
      falls experience (nonfaller group) in the previous 6 months. The participants
      were assessed clinically using the MoCA, the Berg Balance Scale, the Dynamic Gait
      Index (DGI), the Timed Up-and-Go Test, the 10 Meter Walk Test, and the 6 Minute
      Walk Test. The individuals in the nonfaller group performed significantly better
      in all clinical measures than those in the faller group. In the nonfaller group,
      the MoCA was moderately correlated with only two measurements, that is, the 10
      Meter Walk Test and the DGI. In the faller group, the MoCA was moderately
      correlated with four measurements, including the Timed Up-and-Go Test, the 6
      Minute Walk Test, the Berg Balance Test, and the DGI. Physical and cognitive
      functions play a role in falls. Therefore, to decrease the risk of falls among
      community-dwelling stroke patients, clinicians should consider their physical
      activities and cognitive functions irrespective of their falls experience.

PMID- 23165340
TI  - The retina as a window to the brain-from eye research to CNS disorders.
AB  - Philosophers defined the eye as a window to the soul long before scientists
      addressed this cliche to determine its scientific basis and clinical relevance.
      Anatomically and developmentally, the retina is known as an extension of the CNS;
      it consists of retinal ganglion cells, the axons of which form the optic nerve,
      whose fibres are, in effect, CNS axons. The eye has unique physical structures
      and a local array of surface molecules and cytokines, and is host to specialized
      immune responses similar to those in the brain and spinal cord. Several well
      defined neurodegenerative conditions that affect the brain and spinal cord have
      manifestations in the eye, and ocular symptoms often precede conventional
      diagnosis of such CNS disorders. Furthermore, various eye-specific pathologies
      share characteristics of other CNS pathologies. In this Review, we summarize data
      that support examination of the eye as a noninvasive approach to the diagnosis of
      select CNS diseases, and the use of the eye as a valuable model to study the CNS.
      Translation of eye research to CNS disease, and deciphering the role of immune
      cells in these two systems, could improve our understanding and, potentially, the
      treatment of neurodegenerative disorders.

PMID- 23165344
TI  - Other origins for the fluorescence modulation of single dye molecules in open
      circuit and short-circuit devices.
AB  - Fluorescence intensity modulation of single Atto647N dye molecules in a short
      circuit device and a defective device, caused by damaging an open-circuit device,
      is due to a variation in the excitation light focus as a result of the formation
      of an alternating electric current.

PMID- 23165346
TI  - Coupled analysis of steady-state and dynamic characteristics of dye-sensitized
      solar cells for determination of conduction band movement and recombination
      parameters.
AB  - A new research strategy for determining the conduction band movement of TiO(2)
      films and charge recombination between electrons in the TiO(2) film and electron
      acceptors in the electrolyte was proposed. Steady-state short-circuit current
      density versus open-circuit voltage was employed to attain the exchange current
      density and recombination reaction order. Transient photovoltage decay and open
      circuit voltage decay measurements were carried out to obtain the energetic
      distribution of trapped electrons. Reduced voltage-dependent trapped electron
      concentration and trapped electron concentration-dependent recombination current
      density were used to analyze influence factors of open-circuit voltage, including
      contributions from conduction band movement and charge recombination. The
      simulated and measured electron concentration were in agreement and confirmed the
      validity of this method for extracting conduction band movement and recombination
      parameters. This new approach provides a physical insight which could help us to
      more conveniently and efficiently understand the operation of DSCs.

PMID- 23165345
TI  - InP/ZnS as a safer alternative to CdSe/ZnS core/shell quantum dots: in vitro and
      in vivo toxicity assessment.
AB  - We show that water soluble InP/ZnS core/shell QDs are a safer alternative to
      CdSe/ZnS QDs for biological applications, by comparing their toxicity in vitro
      (cell culture) and in vivo (animal model Drosophila). By choosing QDs with
      comparable physical and chemical properties, we find that cellular uptake and
      localization are practically identical for these two nanomaterials. Toxicity of
      CdSe/ZnS QDs appears to be related to the release of poisonous Cd(2+) ions and
      indeed we show that there is leaching of Cd(2+) ions from the particle core
      despite the two-layer ZnS shell. Since an almost identical amount of In(III) ions
      is observed to leach from the core of InP/ZnS QDs, their very low toxicity as
      revealed in this study hints at a much lower intrinsic toxicity of indium
      compared to cadmium.

PMID- 23165347
TI  - Cytotoxicity of herbal extracts used for treatment of prostatic disease on head
      and neck carcinoma cell lines and non-malignant primary mucosal cells.
AB  - Previously, a growth inhibiting effect of PC-Spes on head and neck carcinoma cell
      lines had been demonstrated. In order to determine the toxic impact of particular
      herbs in the mixture, we exposed the head and neck cancer cell lines FADU, HLaC79
      and its Paclitaxel-resistant subline HLaC79-Clone1 as well as primary mucosal
      keratinocytes to increasing concentrations of the herbal mixture Prostaprotect,
      which has a similar formulation as PC-Spes, as well as its single herbal
      components Dendranthema morifolium, Ganoderma lucidium, Glycyrrhiza glabra,
      Isatis indigotica, Panax pseudo-ginseng, Rabdosia rubescens, Scutellaria
      baicalensis and Pygeum africanum. Growth inhibition was measured using the MTT
      assay. Expression of P-glycoprotein (P-GP), multidrug resistance protein-1 (MRP
      1), multidrug resistance protein-2 (MRP-2), breast cancer resistance protein
      (BCRP) and androgen receptor (AR) were examined by western blot analysis. Pygeum
      africanum extract clearly turned out as the main cytotoxic component of the
      Prostaprotect prescription mixture, and initated apoptosis in sensitive cell
      lines. All other extracts had only minor toxic effects. Western blot analysis
      revealed increased expression of P-GP in HLaC79-Clone1 cells, while HLaC79 and
      FADU cells were negative. All three cell lines were negative for MRP-1 and BCRP
      but positive for MRP-2. HLaC79 and its descendant HLaC79-Clone1 both expressed
      AR, as verified by western blotting and immunofluorescence staining. Primary
      mucosal keratinocytes were negative for all multidrug resistance markers as well
      as for AR. Growth inhibition rates of the single herbal extracts were compared
      with previously published results in prostate carcinoma cell lines. The
      relationship between expression levels of AR and multidrug resistance markers in
      relation to the measured toxicity of herbal extracts in our head and neck cancer
      cell system is critically discussed.

PMID- 23165349
TI  - Rigidity and flexibility of biological networks.
AB  - The network approach became a widely used tool to understand the behaviour of
      complex systems in the last decade. We start from a short description of
      structural rigidity theory. A detailed account on the combinatorial rigidity
      analysis of protein structures, as well as local flexibility measures of proteins
      and their applications in explaining allostery and thermostability is given. We
      also briefly discuss the network aspects of cytoskeletal tensegrity. Finally, we
      show the importance of the balance between functional flexibility and rigidity in
      protein-protein interaction, metabolic, gene regulatory and neuronal networks.
      Our summary raises the possibility that the concepts of flexibility and rigidity
      can be generalized to all networks.

PMID- 23165348
TI  - The role of CSM3, MRC1, and TOF1 in minisatellite stability and large loop DNA
      repair during meiosis in yeast.
AB  - Double-stranded break (DSB) repair during meiotic recombination in yeast
      Saccharomyces cerevisiae leads to the formation of heteroduplex DNA, a hybrid DNA
      molecule composed of single strands from two homologous chromosomes. Differences
      in sequence between the strands within heteroduplex DNA generate mismatches or
      large unpaired loops that are substrates for repair. At least two pathways
      function to repair large loops that form within heteroduplex DNA: the RAD1
      dependent large loop repair (LLR) pathway and another as yet uncharacterized RAD1
      independent LLR pathway. Repair of large loops during meiotic recombination is
      especially important for the genomic stability of the repetitive DNA sequences
      known as minisatellites. Minisatellite DNA tracts are generally stable during
      mitotic cell divisions but frequently alter in length during meiosis. Using a
      yeast minisatellite system in which the human minisatellite associated with the
      HRAS1 proto-oncogene has been inserted into the recombination hotspot region
      upstream of HIS4 in S. cerevisiae, our lab previously showed that the RAD1
      dependent LLR pathway controls minisatellite length expansions, but not
      contractions. Here we show that minisatellite length expansions are controlled by
      the products of the CSM3 and TOF1 genes, while contractions are controlled by
      MRC1. By examining meiotic segregation patterns in yeast strains heterozygous for
      the 26bp his4-lopd insert, we found that deleting CSM3 caused a loss of LLR
      activity similar to that seen in a RAD1 mutant. Double mutant analysis revealed
      that failure to repair loops is exacerbated upon deleting both RAD1 and CSM3 -
      specifically the type of repair that fills in loops, which would generate
      minisatellite length expansions. A model for minisatellite length alteration
      based on these results is presented.

PMID- 23165350
TI  - From single splicing events to thousands: the ambiguous step forward in splicing
      research.
AB  - Since the discovery of RNA splicing in 1977 the knowledge of this important
      biological process has increased steadily following the identification of many of
      the mechanistic features of splicing: from the basic cis-acting splicing signals,
      through the detail composition and dynamics of the spliceosome, to the role
      played by accessory splicing factors and their interactions. Moreover, the
      realization that most genes undergo alternative splicing has had a strong impact
      in the overall cell proteome and metabolism research fields and also in better
      appraising the fundamental role played by splicing defects in human disease. This
      robust growth of knowledge is due in particular to the development of new
      powerful technical tools that range from methodologies useful to focus on single
      events in extreme detail to microarray and high-throughput RNA sequencing
      approaches that aim at providing a global vision of splicing changes. Here, we
      will discuss how these techniques relate to each other in terms of their
      respective strengths and weaknesses. In particular, we will focus on their value
      for evaluating the biological significance of splicing events. Finally, we
      provide some views on how these methodologies should move forward to improve our
      basic and applied knowledge of RNA splicing.

PMID- 23165351
TI  - Genomic analysis reveals novel connections between alternative splicing and
      circadian regulatory networks.
AB  - Circadian clocks, the molecular devices present in almost all eukaryotic and some
      prokaryotic organisms, phase biological activities to the most appropriate time
      of day. These devices are synchronized by the daily cycles of light and
      temperature, and control hundreds of processes, ranging from gene expression to
      behavior as well as reproductive development. For a long time, these clocks were
      considered to operate primarily through regulatory feedback loops that act at the
      transcriptional level. Recent studies, however, conclusively show that circadian
      rhythms can persist in the absence of transcription, and it is evident that
      robust and precise circadian oscillations require multiple regulatory mechanisms
      operating at the co-/post-transcriptional, translational, post-translational and
      metabolic levels. Furthermore, these different regulatory loops exhibit strong
      interactions, which contribute to the synchronization of biological rhythms with
      environmental changes throughout the day and year. Here, we describe recent
      advances that highlight the role of alternative splicing (AS) in the operation of
      circadian networks, focusing on molecular and genomic studies conducted in
      Arabidopsis thaliana. These studies have also enhanced our understanding of the
      mechanisms that control AS and of the physiological impact of AS.

PMID- 23165352
TI  - The TP53 signaling network in mammals and worms.
AB  - The nematode worm Caenorhabditis elegans has been an invaluable model organism
      for studying the molecular mechanisms that govern cell fate, from fundamental
      aspects of multicellular development to programmed cell death (apoptosis). The
      transparency of this organism permits visualization of cells in living animals at
      high resolution. The powerful genetics and functional genomics tools available in
      C. elegans allow for detailed analysis of gene function, including genes that are
      frequently deregulated in human diseases such as cancer. The TP53 protein is a
      critical suppressor of tumor formation in vertebrates, and the TP53 gene is
      mutated in over 50% of human cancers. TP53 suppresses malignancy by integrating a
      variety of cellular stresses that direct it to activate transcription of genes
      that help to repair the damage or trigger apoptotic death if the damage is beyond
      repair. The TP53 paralogs, TP63 and TP73, have distinct roles in development as
      well as overlapping functions with TP53 in apoptosis and repair, which
      complicates their analysis in vertebrates. C. elegans contains a single TP53
      family member, cep-1, that shares properties of all three vertebrate genes and
      thus offers a simple system in which to study the biological functions of this
      important gene family. This review summarizes major advances in our understanding
      of the TP53 family using C. elegans as a model organism.

PMID- 23165353
TI  - Predictors of pain among patients with head and neck cancer.
AB  - OBJECTIVE To determine predictors of pain 1 year after the diagnosis of head and
      neck cancer. DESIGN Prospective, multisite cohort study. SETTING Three
      academically affiliated medical centers. PATIENTS The study population comprised
      374 previously untreated patients with carcinoma of the upper aerodigestive
      tract. MAIN OUTCOME MEASURES Participants were surveyed before treatment and 1
      year thereafter. Multivariate analyses were conducted to determine predictors of
      the 36-Item Short-Form Instrument (SF-36) bodily pain score 1 year after
      diagnosis. RESULTS The mean SF-36 bodily pain score at 1 year was 65, compared
      with 61 at the time of diagnosis (P = .004), and 75, the population norm (lower
      scores indicate worse pain). Variables independently associated with pain
      included pretreatment pain score (P < .001), less education (P = .02), neck
      dissection (P = .001), feeding tube (P = .05), xerostomia (P < .001), depressive
      symptoms (P < .001), taking more pain medication (P < .001), less physical
      activity (P = .02), and poor sleep quality (P = .006). The association between
      head and neck cancer pain and current smoking and problem drinking did not reach
      significance (P = .07 and P = .08, respectively). CONCLUSIONS Aggressive pain
      management may be indicated for patients with head and neck cancer who undergo
      neck dissections, complain of xerostomia, require feeding tubes, and have medical
      comorbidities. Treatment of modifiable risk factors such as depression, poor
      sleep quality, tobacco use, and alcohol abuse may also reduce pain and improve
      quality of life among patients with head and neck cancer.

PMID- 23165354
TI  - New strategies for the treatment of lysosomal storage diseases (review).
AB  - The lysosomal storage diseases (LSDs) are a group of inherited metabolic
      disorders caused by the deficiency of any of the lysosomal functions, in most
      cases of lysosomal hydrolases. LSDs are typically characterized by storage of a
      variety of substrates in multiple tissues and organs and by the variable
      association of unusual clinical manifestations that are often responsible for
      physical and neurological handicaps. During the past two decades, research in the
      field of LSDs has made marked progress, particularly with the development of a
      variety of innovative therapeutic approaches. These include several strategies
      aimed at increasing the residual activity of the missing enzyme, such as
      hematopoietic stem cell transplantation, enzyme replacement therapy,
      pharmacological chaperone therapy and gene therapy. An alternative approach is
      based on reducing the synthesis of the stored substrate. More recently, the
      improved knowledge on LSD pathophysiology has indicated additional targets of
      therapy. The recent progress made in the treatment of LSDs represents a good
      model that may be extended to other genetic disorders.

PMID- 23165355
TI  - Fabrication of nanobeads from nanocups by controlling scission/crosslinking in
      organic polymer materials.
AB  - The development of several kinds of micro/nanofabrication techniques has resulted
      in many innovations in the micro/nanodevices that support today's science and
      technology. With feature miniaturization, the fabrication tools have shifted from
      light to ionizing radiation. Here, we propose a simple micro/nanofabrication
      technique for organic materials using a scanning beam (SB) of ionizing radiation.
      By controlling the scission/crosslinking of the material via three-dimensional
      energy-deposition distribution of the SB, appropriate solvents can easily peel
      off only the crosslinked region from the bulk material. The technique was
      demonstrated using a focused ion beam and a chlorinated organic polymer. The
      polymer underwent main-chain scission upon irradiation, but it crosslinked after
      high-dose irradiation. Appropriate solvents could easily peel off only the
      crosslinked region from the bulk material. The technique, 'nanobead from
      nanocup', enabled the production of desired structures such as nanowires and
      nanomembranes. It can be also applied to the micro/nanofabrication of functional
      materials.

PMID- 23165356
TI  - Caring for women with gynecologic cancers around the world: the need for global
      health training in gynecologic oncology fellowship programs.

PMID- 23165357
TI  - American College of Radiology (ACR) and American Society for Radiation Oncology
      (ASTRO) Practice Guideline for Intensity-modulated Radiation Therapy (IMRT).
AB  - Intensity-modulated radiation therapy (IMRT) is a complex technique for the
      delivery of radiation therapy preferentially to target structures while
      minimizing doses to adjacent normal critical structures. It is widely utilized in
      the treatment of a variety of clinical indications in radiation oncology,
      including tumors of the central nervous system, head and neck, breast, prostate,
      gastrointestinal tract, and gynecologic organs, as well as in situations where
      previous radiation therapy has been delivered, and has allowed for significant
      therapeutic advances in many clinical areas. IMRT treatment planning and delivery
      is a complex process. Safe and reliable delivery of IMRT requires appropriate
      process design and adherence to quality assurance (QA) standards. A collaborative
      effort of the American College of Radiology and American Society for Therapeutic
      Radiation Oncology has produced a practice guideline for IMRT. The guideline
      defines the qualifications and responsibilities of all the involved personnel,
      including the radiation oncologist, physicist, dosimetrist, and radiation
      therapist. Factors with respect to the QA of the treatment planning system,
      treatment-planning process, and treatment-delivery process are discussed, as are
      issues related to the utilization of volumetric modulated arc therapy. Patient
      specific QA procedures are presented. Successful IMRT programs involve
      integration of many processes: patient selection, patient
      positioning/immobilization, target definition, treatment plan development, and
      accurate treatment delivery. Appropriate QA procedures, including patient
      specific QA procedures, are essential to ensure quality in an IMRT program and to
      assure patient safety.

PMID- 23165359
TI  - Spondyloarthritis: A conundrum: classifying patients with SpA in daily practice.

PMID- 23165360
TI  - Osteoarthritis: Evaluating strontium ranelate treatment for knee OA.

PMID- 23165361
TI  - Pathology: Autophagy defect traps mutant TNF receptor in TRAPS.

PMID- 23165358
TI  - Facet joint pain--advances in patient selection and treatment.
AB  - Facetogenic pain, also known as zygapophysial joint pain, is a frequent cause of
      mechanical spine pain. Diagnostic blocks (for example, medial branch blocks
      [MBBs]) are the only reliable approach to identify facet joints as the source of
      neck or back pain. In the absence of a reference standard, MBBs actually serve
      more of a prognostic than diagnostic role, enabling the selection of patients who
      might respond to radiofrequency denervation treatment--the standard treatment for
      facet joint pain. Using double blocks reduces the false-positive rate of MBBs,
      but will invariably reduce the overall treatment success rate. No studies have
      evaluated non-interventional treatments for confirmed facetogenic pain, but data
      from studies in non-specific back pain suggest a modest, short-term beneficial
      effect for pharmacotherapy and some non-traditional treatments. Trials of intra
      articular steroid injections for lumbar and cervical facet joint pain have
      yielded disappointing results, but evidence suggests that a subpopulation of
      patients with acute inflammation derive intermediate-term benefit from this
      therapy. Radiofrequency denervation provides some benefit for up to a year in
      approximately 60% of individuals. Increasing this success rate might involve
      enhancing diagnostic specificity and phenotyping, as well as techniques that
      increase the likelihood of successful nerve ablation, such as maximizing lesion
      size.

PMID- 23165362
TI  - Disease activity in patients with long-lasting rheumatoid arthritis is associated
      with changes in peripheral blood lymphocyte subpopulations.
AB  - INTRODUCTION: Rheumatoid arthritis (RA) is a chronic autoimmune disease and it is
      known that lymphocytes play a major role in its pathogenesis. However, there have
      been no comprehensive studies on the changes in peripheral blood lymphocyte (PBL)
      subpopulations expressing different clusters of differentiation (CD) in patients
      with long-lasting RA. OBJECTIVES: The aim of our study was to measure the main
      subpopulations of PBL, expression of costimulatory marker CD28, and activation
      status of CD4+ T cells depending on clinical disease activity in long-lasting RA.
      PATIENTS AND METHODS: The study comprised 60 patients with RA and 19 healthy
      volunteers. Disease activity, the proportion and number of the main PBL
      subpopulations (T, B, natural killer [NK], and NK T cells [NKT]), the expression
      of costimulatory marker CD28, and the activation status of CD4+ T cells were
      evaluated on the same day. A multicolor flow cytometry with marked monoclonal
      antibodies was used for the assessment of lymphocyte subpopulations. RESULTS: The
      percentage of CD3+CD4+, NKT, CD4+CD28-, CD8+CD28-, CD4+CD69+, CD4+CD25+, and
      CD4+HLA-DR+ was significantly higher in RA compared with the control group. A
      higher proportion of CD4+CD28- was associated with more active disease, while an
      inverse correlation was observed for B cells. The proportion of CD4+CD28- was not
      associated with disease activity. The number of CD4+CD69+ cells in RA patients
      increased with increasing DAS28, while the number of CD4+HLA-DR+ T cells showed
      no such association. CONCLUSIONS: Our results have shown for the first time an
      association between the phenotype patterns of PBL T, B, and NKT and RA activity
      in patients with long-lasting disease, which reinforces the hypothesis that PBL
      play an important role in modifying or maintaining the disease activity.

PMID- 23165363
TI  - From time series to biological network regulations: an evolutionary approach.
AB  - In this paper we present a new methodology, based on genetic algorithms and
      multiple linear regression, for discovering regulation mechanisms responsible for
      observed time series in biological networks. The modeling framework employed is
      called Metabolic P systems; they are deterministic and time-discrete dynamical
      systems proposed as an effective alternative to ordinary differential equations
      for modeling biochemical systems. Our methodology is here successfully applied to
      the mitotic oscillator in early amphibian embryos. Starting from the time series
      of substances involved in this system, we are able to reconstruct an MP system
      reproducing the observed dynamics, where the regulatory components were
      discovered by our evolutionary methodology. In particular, genetic algorithms are
      used as a variable selection technique to identify the best representation of any
      regulation function in terms of some given primitive functions.

PMID- 23165364
TI  - Screening of carbonaceous nanoporous materials for capture of nerve agents.
AB  - A strategy for combined experimental and computational screening of candidate
      carbonaceous materials for capturing highly volatile nerve agents at ambient
      temperature using physisorption. Based on theoretical calculations of Henry
      constants and zero-coverage adsorption enthalpies for sarin and DMMP (its common
      stimulant) adsorbed in model slit-shaped carbon pores at 298 K, we found the
      following. Slit-shaped carbon pores with pore width ~0.5 nm are optimal for agent
      adsorption due to strong confinement of adsorbed molecules. Agent adsorption
      enthalpy at zero coverage computed for optimal pore width is very high and
      reaches ~83 kJ mol(-1). Widening of pore width above ~1 nm results in a
      significant decrease of the Henry constant and zero-coverage adsorption enthalpy
      (~44 kJ mol(-1)). Polydispersity of studied candidate carbonaceous materials
      strongly affects adsorption capacity for DMMP under the operating conditions. The
      optimal carbonaceous adsorbent, pitch-based P7 activated carbon fiber, adsorbed
      ~100 MUg g(-1) DMMP at 0.03 MUg m(-3). Commercial Norit activated carbon adsorbed
      only ~20 MUg g(-1) DMMP at 0.03 MUg m(-3). Surprisingly, a small shift of the
      pore size distribution towards wider micropores has a great impact on agent
      adsorption. Because the adsorption enthalpies computed at zero coverage weakly
      dependent on pore size, the heat released during agent adsorption is similar for
      all studied candidate adsorbents (i.e.~55-60 kJ mol(-1)).

PMID- 23165366
TI  - Efficacy and safety of second-generation long-acting injections in schizophrenia:
      a meta-analysis of randomized-controlled trials.
AB  - The aim of the present article is to test at a meta-analytical level the efficacy
      and safety of second-generation long-acting antipsychotic injections (SGLAI) in
      schizophrenia. Thirteen randomized-controlled trials comparing SGLAI with either
      placebo or oral antipsychotics were included in a quantitative meta-analysis
      (6313 patients). Efficacy and safety measures as well as demographic and clinical
      variables were extracted from each publication or obtained directly from authors.
      Publication bias was assessed with funnel plots and Egger's intercept.
      Heterogeneity was addressed with the Q statistic and the I2 index. SGLAI were
      more effective than placebo injections [Hedges's g=0.336, 95% confidence interval
      (CI) 0.246-0.426, Z=7.325, P<0.001] in reducing the Positive and Negative
      Syndrome Scale (PANSS) scores, but no differences were observed compared with
      oral antipsychotics (Hedges's g=0.072, 95% CI -0.072 to 0.217, Z=0.983, P=0.326).
      There were more responders under SGLAI than placebo (47 vs. 24%, NNT 4, 95% CI 3
      6), but no differences in comparison with oral antipsychotics [relative risk
      (RR)=0.962, P=0.094]. SGLAI and controls groups shared a common safety profile
      with respect to the number of deaths, overall number of treatment-adverse events,
      insomnia, QT prolongation, or pain in the injection site. There was a greater
      risk of developing extrapyramidal side effects with SGLAI than with placebo
      (RR=2.037, P<0.001) or with oral antipsychotics (RR=1.451, P=0.048). There was no
      evidence of publication bias (Egger's P=0.476), and sensitivity analysis
      confirmed the robustness of results. The present meta-analysis shows superior
      efficacy for the SGLAI over placebo on psychotic symptoms, although with a
      relatively small effect size; no evidence of superiority in efficacy over oral
      antipsychotics; and modest evidence of greater symptoms of extrapyramidal side
      effects. These data suggest that SGLAI lack an advantage in reducing psychotic
      symptoms over oral medications. Their potential effects on relapse prevention
      should be better addressed by future randomized-controlled trials.

PMID- 23165367
TI  - Regulation of the p53 by Helicobacter pylori.

PMID- 23165368
TI  - Mechanistic investigation of the oxidation of hydrazides: implications for the
      activation of the TB drug isoniazid.
AB  - Aryl hydrazides are oxidised to acyl radicals through a mechanism involving
      diimide intermediates that are prone to nucleophilic acyl substitution. This
      oxidation occurs regardless of the oxidant involved, however there is no evidence
      that the acyl radical formed undergoes further oxidation to the corresponding
      acylium ion, even in the presence of strong oxidants. This study may provide
      insight into the mechanism of isoniazid resistance in Mycobacterium tuberculosis.

PMID- 23165369
TI  - Shape-controlled TiO2 nanoparticles and TiO2 P25 interacting with CO and H2O2
      molecular probes: a synergic approach for surface structure recognition and
      physico-chemical understanding.
AB  - Integrated studies of CO on truncated bipyramidal TiO(2) anatase nanoparticles
      mainly exposing smooth (101) surfaces provide the missing link between TiO(2)
      single crystals and commercial TiO(2) nanopowders with complex morphology. The
      synergy among high resolution transmission electron microscopy, IR spectroscopy
      and modeling correlates adsorbed CO stretching frequency to anatase surface
      types, and reveals how disorder of the adsorbed CO layer affects CO/TiO(2) IR
      bands. Comparison of the two TiO(2) nanoparticle types highlights the role of low
      coordination Ti(4+) sites selectively present on TiO(2) P25 in the photocatalytic
      decomposition of H(2)O(2), an important Reactive Oxygen Species (ROS) formed in
      photocatalytic processes.

PMID- 23165370
TI  - Inactivation of lysyl oxidase by beta-aminopropionitrile inhibits hypoxia-induced
      invasion and migration of cervical cancer cells.
AB  - Tumor invasion and migration are major causes of mortality in patients with
      cervical carcinoma. Tumors under hypoxic conditions are more invasive and have a
      higher metastasic activity. Lysyl oxidase (LOX) is a hypoxia-responsive gene. LOX
      has been shown to be essential for hypoxia-induced metastasis in breast cancer.
      However, the direct impact of LOX on cervical cancer cell motility remains poorly
      understood. Our study revealed that LOX expression at protein and catalytic
      levels is upregulated in cervical cancer cells upon exposure to hypoxia. Hypoxia
      induced mesenchymal-like morphological changes in HeLa and SiHa cells which were
      accompanied by upregulation of alpha-SMA and vimentin, two mesenchymal markers,
      and downregulation of E-cadherin, an epithelial marker, indicating the epithelial
      mesenchymal transition (EMT) of cervical cancer cells occurred under hypoxic
      conditions. Treatment of tumor cells with beta-aminopropionitrile (BAPN), an
      active site inhibitor of LOX, blocked the hypoxia-induced EMT morphological and
      marker protein changes, and inhibited invasion and migration capacities of
      cervical carcinoma cells in vitro. Collectively, these findings suggest LOX
      enhances hypoxia-induced invasion and migration in cervical cancer cells mediated
      by the EMT which can be inhibited by BAPN.

PMID- 23165371
TI  - Forty years of USAID health cooperation in Bolivia. A lose-lose game?
AB  - The present article proposes an analysis of the USA-Bolivia relationships in the
      health sector between 1971 and 2010 based on a grey and scientific literature
      review and on interviews. We examined United States Agency for International
      Development (USAID) interventions, objectives, consistency with Bolivian needs,
      and impact on health system integration. USAID operational objectives-
      decentralization, fertility and disease control, and maternal and child health-
      may have worked against each other while competing for limited Ministry of Health
      resources. They largely contributed to the segmentation and fragmentation of the
      Bolivian health system. US cooperation in health did not significantly improve
      health status while the USAID failed to properly tackle anti-drugs, political,
      and economic US interests in Bolivia.

PMID- 23165374
TI  - Surgical margins in the genomic era: The Hayes Martin Lecture, 2012.
AB  - One of the highest honors of one's career is to be asked to address colleagues,
      mentors, and students who represent the world's leading health professionals
      dedicated to reducing the morbidity and mortality associated with head and neck
      cancer. Hayes Martin would certainly share this feeling of honor and humility in
      having a lecture given in his name on the occasion of the Eighth International
      Conference on Head and Neck Cancer. I am so very pleased to share with you some
      thoughts on the assessment, adequacy, and application of surgical resection
      margins in an era in which personalized surgery and molecular medicine will have
      a major impact on patient outcomes. My thoughts about surgical margins have
      evolved over nearly 40 years of performing surgical resections for cancer. A
      discussion of margins may seem somewhat mundane to many of you; however, I hope
      to provide a futuristic and somewhat theoretical view of how surgical margin
      issues will relate to the personalization of modern head and neck cancer
      treatment and how the biology of the tumor microenvironment may be instructive in
      the application of our surgical approaches. This is particularly relevant because
      of the rapid expansion of functional surgical approaches utilizing minimally
      invasive endoscopic resections and robotic techniques that may not achieve the
      same wide oncologic margins that have been emphasized historically.(1,2) Proper
      selection of patients for such procedures is critical if we are to improve
      overall treatment results.

PMID- 23165375
TI  - The effect of hospital safety-net burden status on short-term outcomes and cost
      of care after head and neck cancer surgery.
AB  - OBJECTIVE: To determine the association between safety-net hospital care and
      short-term outcomes after head and neck cancer surgery. DESIGN: Cross-sectional
      analysis. Safety-net burden was calculated as the percentage of patients with
      head and neck cancer with Medicaid or no insurance. SETTING: Nationwide Inpatient
      Sample database. PATIENTS: Adults who underwent an ablative procedure for a
      malignant oral cavity, laryngeal, hypopharyngeal, or oropharyngeal neoplasm in
      2001 through 2008. MAIN OUTCOME MEASURES: Associations between hospital safety
      net burden and short-term morality, medical and surgical complications, length of
      hospitalization, and costs. RESULTS: Overall, 123 662 patients underwent surgery
      in 2001 through 2008. Patients treated at high-safety-net burden hospitals were
      significantly more likely to be admitted urgently or emergently (odds ratio [OR],
      1.54; 95% CI, 1.06-1.15 [P = .03]), undergo major surgical procedures (OR, 1.24;
      95% CI, 1.09-1.39 [P = .001]), have advanced comorbidity (OR, 1.35; 95% CI, 1.06
      1.72 [P = .02]), and be black (OR, 1.70; 95% CI, 1.29-2.23 [P < .001]), but less
      likely to be elderly (OR, 0.66; 95% CI, 0.53-0.82 [P < .001]). High safety-net
      burden hospitals were significantly more likely to be teaching hospitals (OR,
      2.04; 95% CI, 1.26-3.29 [P = .004]) and less likely to be located in the West
      (OR, 0.18; 95% CI, 0.07-0.44 [P < .001]). Safety-net burden was not associated
      with in-hospital mortality, acute medical complications, surgical complications,
      or hospital-related costs after controlling for all other variables including
      hospital volume status, but was associated with a mean increase in length of
      hospitalization of 24 hours (P < .001). CONCLUSIONS: These data suggest that
      safety-net hospitals provide valuable specialty care to a vulnerable population
      without an increase in complications or costs. Health care reform must address
      the economic challenges that threaten the viability of these institutions at the
      same time that demand for their services increases.

PMID- 23165376
TI  - Predictors of level II and Vb neck disease in metastatic papillary thyroid
      cancer.
AB  - OBJECTIVE: To identify predictors of levels II and Vb involvement in papillary
      thyroid cancer (PTC) with lateral neck metastasis. DESIGN: Large case series.
      SETTING: High-volume tertiary care hospital. PATIENTS: Consecutive sample of 185
      patients who underwent 248 selective neck dissections of at least levels II to V
      for pathologically proven PTC. MAIN OUTCOME MEASURES: Significant independent
      predictors of level II and Vb metastasis, including age and pathologic variables
      (tumor diameter, dominant nodule cellular pathology, multifocality, extracapsular
      invasion, positive margins, and lymphovascular invasion). RESULTS: Levels II and
      Vb were involved in 49.3% and 29.2% of our cohort, respectively. Age and
      lymphovascular invasion were independent predictors of level Vb involvement with
      metastasis (logistic regression: odds ratio for age = 0.92, SE = 0.03, P = .02;
      and odds ratio for lymphovascular invasion = 5.52, SE = 0.80, P = .03). No
      significant predictors were identified for level II involvement. CONCLUSIONS:
      Levels II and Vb were involved in a significant number of patients with PTC and
      lateral neck disease. Younger age and lymphovascular involvement were independent
      risk factors for level Vb involvement in patients with PTC and lateral neck
      metastasis. The increased risk might be of marginal clinical significance. No
      significant predictors were identified for level II involvement. Our findings do
      not favor a limited neck dissection on the basis of any of the study's clinical
      or pathologic variables, and we therefore recommend the routine excision of
      levels IIa to Vb in all patients with PTC presenting with lateral neck disease.

PMID- 23165377
TI  - Significant invasion of the pharyngeal constrictor muscle in early squamous cell
      carcinoma of the tonsil: prediction of multiple regional metastasis.
AB  - OBJECTIVE: To determine whether invasion of the pharyngeal constrictor muscle in
      early squamous cell carcinoma of the tonsil is correlated with lymph node
      metastasis. DESIGN: Retrospective analysis of medical records and pathology
      specimens. SETTING: Tertiary care referral center. PATIENTS: Forty-eight patients
      who were diagnosed as having T2 squamous cell carcinoma of the tonsil and who
      underwent surgery. They were divided into 2 groups: an invasive group with
      invasion of the pharyngeal constrictor muscle and a noninvasive group without
      invasion of the pharyngeal constrictor muscle. MAIN OUTCOME MEASURES: Comparison
      of regional metastasis, 5-year locoregional recurrence, and 5-year disease
      specific survival between the 2 groups. RESULTS: Invasion of the pharyngeal
      constrictor muscle was found in 36 patients (75%) with T2 squamous cell carcinoma
      of the tonsil. The rate of lymph node metastasis, the mean (SD) number of
      positive nodes, and the mean (SD) lymph node density were 81%, 5.47 (9.27), and
      0.15 (0.22) in the invasive group, respectively, and 50%, 1.33 (1.72), and 0.04
      (0.04) in the noninvasive group, respectively (P = .04, P = .02, and P = .01,
      respectively). Five-year locoregional recurrence was significantly correlated
      with invasion of the pharyngeal constrictor muscle (P = .05) and with multiple
      lymph node metastasis (>=5 nodes) (P = .04) in the univariate analyses. No factor
      was correlated with 5-year locoregional recurrence in the multivariate analysis.
      Five-year disease-specific survival was significantly correlated with multiple
      lymph node metastasis (>=5 nodes) in the univariate analyses (P = .009). Five
      year disease-specific survival was not significantly correlated with any
      clinicopathological factor in the multivariate analysis. CONCLUSION: Higher risk
      for multiple lymph node metastasis and 5-year locoregional recurrence seems to be
      predicted in patients with extratonsillar invasion of the pharyngeal constrictor
      muscle, even in early squamous cell carcinoma of the tonsil.

PMID- 23165379
TI  - Outcomes of adenotonsillectomy in patients with Prader-Willi syndrome.
AB  - OBJECTIVE: To assess the efficacy of upper airway surgical intervention in
      patients with Prader-Willi syndrome (PWS). Due to reports of sudden death in
      children undergoing treatment with growth hormone for PWS, detection of sleep
      disordered breathing by polysomnography (PSG) has been recommended. DESIGN:
      Retrospective study. SETTING: Multidisciplinary PWS Center at a tertiary care
      children's hospital. PATIENTS: Thirteen pediatric patients with PWS who underwent
      adenotonsillectomy (T&A) with pre-PSG and post-PSG. MAIN OUTCOME MEASURES:
      Comparison of PSG results before and after T&A. RESULTS: Six of our patients were
      girls (46%); 8 had genetic characteristics consistent with deletion (61%), and
      the remaining 5 had genetic characteristics consistent with uniparental disomy
      (39%). The median age at T&A was 3 years (age range, 6 months to 11 years), and
      the median age at start of growth hormone treatment was 8.5 months (range, 2
      months to 6 years). Nine of the 13 patients had mild to moderate obstructive
      sleep apnea (OSA) or obstructive hypoventilation (69%); in 8 of these 9,
      breathing normalized after T&A. Four children had severe OSA prior to surgery
      (31%). Breathing normalized in 2 of these after surgery, but 2 had PSG findings
      of residual combined obstructive and central apneas postoperatively. CONCLUSIONS:
      Adenotonsillectomy, while effective in most children with PWS who demonstrate
      mild to moderate OSA, may not be curative in children with severe OSA. An
      increase in central apneas can occur in some children with PWS postoperatively,
      and it is important to repeat PSG after surgery. Further studies are necessary to
      determine optimal treatment for some children with PWS and sleep-disordered
      breathing.

PMID- 23165378
TI  - Retrospective review of positron emission tomography with contrast-enhanced
      computed tomography in the posttreatment setting in human papillomavirus
      associated oropharyngeal carcinoma.
AB  - OBJECTIVE: To determine the value of positron emission tomography (PET) with
      contrast-enhanced computed tomography (CT) in assessing the need for neck
      dissection by retrospectively reviewing the pathology reports of patients with
      human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma
      (SCC). DESIGN: Retrospective cohort study. SETTING: Tertiary medical center.
      PATIENTS: Seventy-seven patients with HPV-related SCC. MAIN OUTCOME MEASURES:
      Seventy-seven consecutive patients with a diagnosis of HPV-related SCC who were
      treated with radiotherapy as the primary treatment between August 2007 and
      October 2010 were retrospectively evaluated for radiologic and pathologic rate of
      persistence of nodal metastasis after completion of definitive radiotherapy.
      Pretreatment and posttreatment imaging included contrast-enhanced CT and PET.
      Response to treatment was measured on CT, PET at standardized uptake value (SUV)
      thresholds of 2 and 2.5, and PET/CT by a neuroradiologist in a blinded fashion.
      Then, the pathology report of the patients who underwent neck dissections was
      reviewed for nodal status after resection and correlated with the imaging
      findings. RESULTS: Of the 77 patients, 67 met the study criteria, with an average
      follow-up PET/CT scan at 90.5 days after completion of radiotherapy. Ten patients
      did not undergo follow-up PET/CT imaging. Twenty patients underwent neck
      dissections after completion of radiation therapy. Of these 20 patients, 4 had
      persistent tumor and 16 did not have viable tumor. Using the final pathology
      report to correlate with imaging responses, CT had a negative predictive value
      (NPV) of 85.7% (95% CI, 48.7%-97.4%), PET with SUV thresholds of 2 had an NPV of
      91.7% (95% CI, 64.6%-98.5%), PET with a cutoff SUV of 2.5 had an NPV of 85.7%
      (95% CI, 60.1%-96.0%), PET/CT with an SUV of 2 had an NPV of 100% (95% CI, 59.8%
      100.0%), and PET/CT with an SUV of 2.5 had an NPV of 85.7% (95% CI, 48.7%-97.4%).
      The 47 patients who did not undergo neck dissection had a median follow-up of 26
      months without an isolated neck failure. Analysis of all 67 patients in the
      cohort revealed the following values: CT had an NPV of 95.7% (95% CI, 85.8%
      98.8%), PET with an SUV of 2 had an NPV of 98.2% (95% CI, 90.4%-99.7%), PET with
      an SUV of 2.5 had an NPV of 95.0% (95% CI, 86.3%-98.3%), PET/CT with an SUV of 2
      had an NPV of 100.0% (95% CI, 92.0%-100.0%), and PET/CT with an SUV of 2.5 had an
      NPV of 95.7% (95% CI, 85.8%-98.8%). CONCLUSIONS: Positron emission tomography
      combined with contrast-enhanced CT has a better NPV than either imaging modality
      alone in patients with HPV-associated oropharyngeal SCC. Furthermore, PET/CT with
      an SUV threshold of 2 used in patients with HPV-related SCC offers an imaging
      modality with a high NPV that may obviate the need for unnecessary neck
      dissections.

PMID- 23165380
TI  - Diagnostic and prognostic utility of measuring tumor necrosis factor in the
      peripheral circulation of patients with immune-mediated sensorineural hearing
      loss.
AB  - OBJECTIVES: To characterize levels of tumor necrosis factor (TNF; formerly known
      as tumor necrosis factor alpha), a well-established proinflammatory cytokine, in
      patients with immune-mediated sensorineural hearing loss (IM-SNHL) and to
      determine the role of this cytokine in identifying steroid-responsive hearing
      loss. DESIGN: Prospective case-control study. SETTING: Tertiary care academic
      medical center. PATIENTS: A total of 11 control subjects and 85 patients with
      clinical and audiometric characteristics of IM-SNHL (autoimmune inner ear disease
      and sudden SNHL combined) treated with corticosteroids were enrolled in the
      study. Patients were categorized as steroid responders (n = 47) and steroid
      nonresponders (n = 38). Peripheral venous blood was used to determine the total
      amount of plasma TNF by enzyme-linked immunosorbent assay. Peripheral blood
      mononuclear cells (PBMCs) were isolated and treated with in vitro dexamethasone.
      Treated and untreated PBMCs were then analyzed for release of soluble TNF protein
      into conditioned supernatants as well as expression of TNF messenger RNA (mRNA).
      MAIN OUTCOME MEASURES: Mean plasma levels of TNF, unstimulated and dexamethasone
      stimulated PBMC-secreted levels of TNF, and TNF mRNA levels in unstimulated and
      dexamethasone-stimulated PBMCs. RESULTS: Steroid nonresponders had the highest
      mean baseline plasma levels of TNF compared with steroid responders and control
      subjects (27.6, 24.1, and 14.4 pg/mL, respectively) (P = .03). For patients with
      IM-SNHL with a high baseline plasma levels of TNF (>14.4 pg/mL), the mean TNF
      secreted by PBMCs was 59.1 pg/mL, which decreased to 7.2 pg/mL with in vitro
      dexamethasone stimulation in the responder group, while the mean TNF secreted by
      PBMCs was 11.2 pg/mL, which slightly increased to 11.7 pg/mL with in vitro
      dexamethasone stimulation in the nonresponder group (P = .04). CONCLUSIONS: The
      level of TNF can be used as both a diagnostic and prognostic cytokine for IM
      SNHL. For patients presenting with a sudden change in hearing threshold, a high
      baseline plasma TNF from the peripheral circulation is supportive of the
      diagnosis if it is greater than 18.8 pg/mL, with a positive predictive value
      higher than 97%. In addition, this study demonstrates that for patients with IM
      SNHL and high plasma levels of TNF, their clinical response to oral
      glucocorticoids can be predicted by their in vitro PBMC response to
      dexamethasone. This algorithm may further guide optimal medical treatment and
      possibly avoid the deleterious adverse effects of administering glucocorticoids
      to those patients who would not benefit from their effect.

PMID- 23165381
TI  - Intranasal theophylline treatment of hyposmia and hypogeusia: a pilot study.
AB  - OBJECTIVE: To determine whether intranasal theophylline methylpropyl paraben can
      correct hyposmia and hypogeusia. DESIGN: We performed an open-label pilot study
      in patients with hyposmia and hypogeusia under the following 3 conditions: (1)
      before treatment, (2) after oral theophylline anhydrous treatment, and (3) after
      intranasal theophylline treatment. Under each condition, we performed subjective
      evaluations of taste and smell functions, quantitative measurements of taste
      (gustometry) and smell (olfactometry), and measurements of serum theophylline
      level and body weight. SETTING: The Taste and Smell Clinic in Washington, DC.
      PATIENTS: Ten patients with hyposmia and hypogeusia clinically related to the
      effects of viral illness, allergic rhinitis, traumatic brain injury, congenital
      hyposmia, and other chronic disease processes were selected. INTERVENTIONS: Oral
      theophylline anhydrous, 200 to 800 mg/d for 2 to 12 months, was administered to
      each patient. This treatment was discontinued for 3 weeks to 4 months when
      intranasal theophylline methylpropyl paraben, 20 MUg/d in each naris, was
      administered for 4 weeks. MAIN OUTCOME MEASURES: At termination of each
      condition, taste and smell function was determined subjectively, by means of
      gustometry and olfactometry, with measurement of serum theophylline levels and
      body weight. RESULTS: Oral theophylline treatment improved taste and smell acuity
      in 6 patients after 2 to 12 months of treatment. Intranasal theophylline
      treatment improved taste and smell acuity in 8 patients after 4 weeks, with
      improvement greater than after oral administration. No adverse effects
      accompanied intranasal drug use. Body weight increased with each treatment but
      was greater after intranasal than after oral administration. CONCLUSIONS:
      Intranasal theophylline treatment is safer and more effective in improving
      hyposmia and hypogeusia than oral theophylline anhydrous treatment.

PMID- 23165382
TI  - Improvements in sensorineural hearing loss after cord blood transplant in
      patients with mucopolysaccharidosis.
AB  - OBJECTIVE: To objectively determine changes in sensorineural hearing in children
      with mucopolysaccharidosis (MPS) by comparing audiological data before and after
      hematopoietic stem cell transplantation (HSCT). DESIGN: Retrospective medical
      chart analysis. SETTING: Tertiary referral hospital. PATIENTS: Thirty pediatric
      patients with the diagnosis of MPS who underwent HSCT and had audiological data
      before and after HSCT. Data were extracted from medical charts for patients seen
      at our institution from January 1, 1999, to December 1, 2009. MAIN OUTCOMES
      MEASURES: Hearing was assessed using behavioral audiometry testing and auditory
      brainstem responses (ABR) before and after HSCT. Patient demographics, diagnosis,
      and age at HSCT were also evaluated. RESULTS: Thirty patients with MPS were
      included. Four (13%) had MPS type 3a, 2 (7%) had MPS type 2, and 24 (80%) had MPS
      type 1. The average age at HSCT was 19 months (range, 5-44 months). Hearing
      improvement was evaluated by audiogram (20 patients), ABR (8 patients), and
      qualitative measures (30 patients). On average, patients did not show improvement
      on audiogram (P = .28; paired t test). The ABR click threshold improved 19 dB on
      average (P < .001). Qualitatively, 3 patients had normal hearing before and after
      HSCT. Of the remaining 27 patients, 20 (67%) showed improvement in sensorineural
      hearing (P < .001). Five (17%) had hearing loss and did not improve. Two (7%) had
      worsening hearing. Hematopoietic stem cell transplantation at the age of 25
      months or younger was significantly correlated with hearing improvement (P =
      .03). CONCLUSIONS: Hematopoietic stem cell transplantation may provide
      improvement in MPS-associated sensorineural hearing loss. Hearing improvement is
      more likely to occur in patients who undergo transplantation at 25 months or
      younger.

PMID- 23165383
TI  - Balloon dilation of the sinuses.

PMID- 23165384
TI  - To balloon or not to balloon?

PMID- 23165385
TI  - Gongylonema: a parasitic nematode of the oral cavity.
AB  - We report a rare parasitic nematode infection in a 26-year-old healthy African
      American man. Gongylonema nematode infections in humans are unique in their
      ability to localize in the submucosa of the oral cavity and oropharynx. Humans
      are incidental hosts for the Gongylonema nematode, which is more commonly found
      in rudimentary animals, birds, and rodents. Approximately 50 cases of human
      Gongylonema infections have been reported worldwide, including 11 documented
      cases in the United States.(1) The pathogenesis, characteristic clinic findings,
      and identification features will be discussed.

PMID- 23165386
TI  - Radiology quiz case 1. Diagnosis: Cholesteatoma of the frontal sinus.

PMID- 23165388
TI  - Radiology quiz case 2. Diagnosis: Middle ear hemangioma.

PMID- 23165390
TI  - Pathology quiz case 1. Diagnosis: Intravascular papillary endothelial hyperplasia
      (IPEH).

PMID- 23165392
TI  - Pathology quiz case 2. Diagnosis: Papillary thyroid carcinoma arising in the
      setting of black thyroid.

PMID- 23165394
TI  - Coronary artery calcium in type 2 diabetes: a nested case-control study.
AB  - INTRODUCTION: The use of classic risk scores in patients with type 2 diabetes
      have numerous limitations. Relationships between coronary artery calcium score
      (CACS) and traditional risk factors are derived from statistical analyses. At
      present, there are no data on the evaluation of the CACS on 64-slice multi
      detector computed tomography in patients with type 2 diabetes and ischemic
      symptoms based on a head-to-head comparison with matched nondiabetics.
      OBJECTIVES: We aimed to examine the associations between traditional risk factors
      and the CACS in a nested case-control study. PATIENTS AND METHODS: We performed a
      retrospective analysis of data from 2482 consecutive symptomatic subjects with
      known CACS. We identified 325 patients with type 2 diabetes. From the remaining
      subjects, 325 controls matched for age, sex, and risk factors were selected.
      RESULTS:  Higher CACS values were observed in patients with diabetes (median, 50
      Agatston units [AU]; range, 0-4330) compared with nondiabetic controls (9 AU, 0
      3036, P <0.001). Positive CACS values were more common in diabetic patients
      (73.5%) compared with nondiabetic controls (60.9%, P <0.001). The highest CACS
      value was observed in men (95.5 AU, 0-3755). The median CACS value in nondiabetic
      men was comparable to those in diabetic women (24.5 AU, 0-3036 vs. 24.5 AU, 0
      3755). The lowest CACS values were observed in control women (3 AU, 0-2144).
      Coronary artery calcium was more diffused in diabetic patients compared with
      controls (P <0.01). A multivariate analysis showed that older age and male sex
      were independent predictors of the CACS. Traditional risk factors accounted only
      for 10% of interindividual variance in the presence of calcified atherosclerotic
      plaques. CONCLUSIONS: Coronary calcified lesions are more frequent in symptomatic
      patients with type 2 diabetes compared with matched nondiabetic subjects. Our
      results seem to provide evidence that traditional risk factors do not explain
      more common, diffuse, and extensive calcified lesions in diabetic subjects.

PMID- 23165395
TI  - Arrays of nanoelectromechanical biosensors functionalized by microcontact
      printing.
AB  - The biofunctionalization of nanoelectromechanical systems (NEMS) is critical for
      the development of new classes of biosensors displaying improved performance and
      higher levels of integration. In this paper we propose a modified microcontact
      process (MUCP) in order to biofunctionalize arrays of NEMS with a probe molecule
      on the active sensing areas together with an anti-fouling layer on the passive
      areas in a single, self-aligned step. We demonstrate the adequate
      functionalization/anti-fouling of arrays of freestanding nanocantilevers as dense
      as 10(5) nanostructures cm(-2) by using both fluorescence microscopy and dynamic
      measurements of the structures' resonant frequency. The proper bioactivity of an
      antibody deposited onto the cantilevers and the blocking property of a bovine
      serum albumin layer are both assessed by incubating specific and non-specific
      tagged secondary antibodies followed by fluorescence imaging. Furthermore,
      measurement of the resonant frequency of the nanocantilevers before and after
      functionalization and biological recognition demonstrate that using MUCP for
      device functionalization does not damage the nanostructures and preserves the
      mechanical sensing capability of our NEMS.

PMID- 23165397
TI  - Prostate cancer: 'Galectin signature' reveals gal-1 as key player in
      angiogenesis.

PMID- 23165396
TI  - The link between benign prostatic hyperplasia and prostate cancer.
AB  - Benign prostatic hyperplasia (BPH) and prostate cancer are among the most common
      diseases of the prostate gland and represent significant burdens for patients and
      health-care systems in many countries. The two diseases share traits such as
      hormone-dependent growth and response to antiandrogen therapy. Furthermore, risk
      factors such as prostate inflammation and metabolic disruption have key roles in
      the development of both diseases. Despite these commonalities, BPH and prostate
      cancer exhibit important differences in terms of histology and localization.
      Although large-scale epidemiological studies have shown that men with BPH have an
      increased risk of prostate cancer and prostate-cancer-related mortality, it
      remains unclear whether this association reflects a causal link, shared risk
      factors or pathophysiological mechanisms, or detection bias upon statistical
      analysis. Establishing BPH as a causal factor for prostate cancer development
      could improve the accuracy of prognostication and expedite intervention,
      potentially reducing the number of men who die from prostate cancer.

PMID- 23165398
TI  - Sexual dysfunction: The potential of stem cell therapy for Peyronie disease.

PMID- 23165399
TI  - Preventing stone retropulsion during intracorporeal lithotripsy.
AB  - Several studies of ureteroscopic treatment for ureteral stones have reported that
      most stone clearance failures can be attributed to stone fragment retropulsion.
      Stone retropulsion can result in increased operative time and cost-resulting from
      the need to change from the semi-rigid ureteroscope to a flexible instrument to
      chase migrated calculi-and additional procedures to treat residual migrated
      fragments are often required. The degree of migration depends mainly on the
      energy source used for lithotripsy; pneumatic and electrohydraulic lithotripters
      are associated with a greater degree of retropulsion than lasers. Different stone
      trapping strategies and devices have been developed to minimize stone migration.
      Novel devices include the Lithovac((r)) suction device, the Passport(TM) balloon,
      the Stone Cone(TM), the PercSys Accordion((r)), the NTrap((r)), and stone baskets
      such as the LithoCatch(TM), the Parachute(TM), and the Escape((r)). Some authors
      have also reported on the use of lubricating jelly and BackStop((r)) gel (a
      reverse thermosensitive polymeric plug); these devices are instilled proximal to
      the stone prior to the application of kinetic energy in order to prevent
      retrograde stone migration.

PMID- 23165401
TI  - Bladder cancer: Toxic effects--a BCG balancing act.

PMID- 23165402
TI  - Surgery: Tranexamic acid reduces bleeding during percutaneous nephrolithotomy.

PMID- 23165400
TI  - Insight into oxidative stress in varicocele-associated male infertility: part 2.
AB  - Varicocele, the leading cause of male infertility, can impair spermatogenesis
      through several pathophysiological mechanisms. Of these, current evidence
      suggests that oxidative stress is the central element contributing to infertility
      in men with varicocele, to which the testis responds by way of heat stress,
      ischaemia or production of vasodilators, such as nitric oxide. Surgical
      varicocele repair (varicocelectomy) is beneficial not only for alleviating
      oxidative stress-associated infertility, but also for preventing and protecting
      against the progressive character of varicocele and its consequent upregulations
      of systemic oxidative stress. However, antioxidant therapy in infertile men with
      surgically treated and those with untreated varicocele is poorly studied, and
      well-designed trials are needed.

PMID- 23165404
TI  - Bladder cancer: Lack of progress in bladder cancer--what are the obstacles?

PMID- 23165405
TI  - Prostate cancer: the androgen receptor-a novel target for vaccines.

PMID- 23165406
TI  - Theoretical investigation on Pt(II)- and Au(I)-mediated cycloisomerizations of
      propargylic 3-indoleacetate: [3 + 2]- versus [2 + 2]-cycloaddition products.
AB  - With the aid of density functional theory (DFT) calculations, we have performed a
      detailed mechanism study for the catalytic cycloisomerization reactions of
      propargylic 3-indoleacetate to better understand the observed divergent
      reactivities of two catalysts, PtCl(2) and (PPh(3))AuSbF(6), which result in [3 +
      2]- and [2 + 2]-cycloaddition products, respectively. The calculated results
      confirm that the lactone intermediates are common and necessary species for the
      formation of the two products and that PtCl(2) and (PH(3))AuSbF(6) respectively
      favor the formation of the [3 + 2]- and [2 + 2]-products. The intrinsic reasons
      for the divergent reactivities of the two catalysts have been analyzed in detail.
      We believe that the essentially different metal-ligand interactions in PtCl(2)
      and (PPh(3))AuSbF(6) are mainly responsible for their divergent
      regioselectivities, while the solvent effects have little impact on the catalyst
      activity. Starting from lactone intermediates, PtCl(2) induces the intramolecular
      nucleophilic addition to give the [3 + 2] cycloisomerization product due to the
      strong pi-electron-donating ability of chlorine ligands, while (PPh(3))AuSbF(6)
      results in the intramolecular nucleophilic addition reaction to form the [2 + 2]
      cycloisomerization product because of the strong sigma-electron-donating ability
      of phosphine ligands.

PMID- 23165403
TI  - Insight into oxidative stress in varicocele-associated male infertility: part 1.
AB  - Varicocele is recognized as the leading cause of male infertility because it can
      impair spermatogenesis through several distinct pathophysiological mechanisms.
      Current evidence supports oxidative stress as a key element in the
      pathophysiology of varicocele-related infertility, although these mechanisms have
      not yet been fully described. Measurement of the reactive oxygen species and
      other markers of oxidative stress, including the levels of the antioxidant
      enzymes catalase and superoxide dismutase, can provide valuable information on
      the extent of oxidative stress and might guide therapeutic management strategies.
      The testis can respond to varicocele-associated cell stressors, such as heat
      stress, ischaemia or production of vasodilators (for example, nitric oxide) at
      the expense of the generation of excessive reactive oxygen species. These
      responses have their own implications in exacerbating the underlying oxidative
      stress and on the subsequent infertility.

PMID- 23165407
TI  - Simple naphthalimide-based fluorescent sensor for highly sensitive and selective
      detection of Cd2+ and Cu2+ in aqueous solution and living cells.
AB  - A novel naphthalimide-based fluorescent sensor bearing the N,N'
      bis(salicylidene)diethylenetriamine receptor was developed, which exhibited dual
      signaling behaviors for Cd(2+) and Cu(2+), and was applicable to the
      environmental and biological milieus. Upon addition of Cd(2+), the fluorescence
      intensity enhanced in a linear fashion with the maximum fluorescence intensity
      increase of about 4-fold. Moreover, with the sensor 1 and 1-Cd(2+) complex,
      Cu(2+) was easily recognized by marked fluorescence quenching. The selectivity
      and sensitivity of the sensor 1 for Cd(2+) were satisfactory and achieving a
      detection limit at the nanomolar level. The living cell image experiments
      demonstrated the value of sensor 1 in fluorescent visualization of Cd(2+) ions in
      biological systems.

PMID- 23165408
TI  - Prevalence and clinical characteristics of adult patients with congenital heart
      disease in Tuscany.
AB  - AIMS: The clinical features of the adult population with congenital heart disease
      (CHD) are still not well characterized, particularly in the subset with more
      severe lesions. We report the data collected in the National Association of
      Hospital Cardiologists Toscana grown-up CHD (GUCH) registry over its first 8
      month enrolment period. METHODS: The Registry included consecutive patients aged
      more than 16 years with a documented diagnosis of CHD, enrolled in seven
      different Tuscan hospitals using a web-based electronic form. Severe CHD was
      defined as cyanotic CHD, or acyanotic lesion with significant haemodynamic impact
      requiring surgical and/or percutaneous correction. RESULTS: Between November 2009
      and June 2010 a total of 1641 patients (mean age 41.8 +/- 19.3 years, 52.2%
      women) were enrolled. Atrial septal defect was the most common lesion, accounting
      for more than one-third of cases. Atrial and ventricular septal defects together
      accounted for about half of all CHDs. Nearly one-third of patients had New York
      Heart Association (NYHA) class 2 or more. A history of recurrent arrhythmias was
      reported in 15% of cases, and 12% of patients were on oral anticoagulants at the
      time of enrolment. The prevalence of pulmonary hypertension was 6%, and the
      prevalence of Eisenmenger syndrome was 1.2%. Severe CHD was present in 42% of
      patients. Younger age, higher NYHA class, male sex, and the need for oral
      anticoagulants were the only independent predictors of severe CHD. CONCLUSION:
      Information about the clinical characteristics and the CHD type distribution of a
      sample of Tuscan GUCH population was provided. Severe CHD accounts for about 40%
      of all CHDs in this population. CHD severity is associated with younger age, male
      gender, worse NYHA class, and need for oral anticoagulation.

PMID- 23165410
TI  - Cognitive and executive functions in ADHD.
AB  - INTRODUCTION: Some studies have reported that attention-deficit/hyperactivity
      disorder (ADHD) children show alterations in different cognitive functions.
      Recently, a deficiency in the executive functions (EF) is proposed as the cause
      underlying all of these symptoms. However discrepancies exist about these
      findings. OBJECTIVE: Assessment of cognitive and executive functions of subjects
      with both ADHD hyperactive-impulsive type and combined type, in order to reveal
      their neuropsychological characteristics and analyze if those functions are
      related to hyperactive-impulsive behavior. METHOD: Neuropsychological Battery,
      Stroop test, Wisconsin Card Sorting test and London Tower test were applied to 51
      children between 7 and 12 years old (25 controls and 26 ADHD). RESULTS: ADHD
      children showed worst performance in sustained attention, rapid serial naming of
      figures and colors, comprehension of written instructions, word dictation, number
      comparison, arithmetical problems, visual working memory, long term memory and
      the scores of WCST. Variables related to hyperactivity-impulsivity were: errors
      and decreased velocity in rapid serial naming of colors and figures,
      comprehension of written instructions, arithmetical problems and the scores of
      total errors, perseverating errors and perseverating responses of WCST.
      CONCLUSION: ADHD children show a great variety of cognitive deficiencies and had
      deficit only in some domains of executive functions. These deficiencies could
      explain to some extent the hyperactive and impulsive behavior.

PMID- 23165409
TI  - High-throughput chemical screens identify disulfiram as an inhibitor of human
      glioblastoma stem cells.
AB  - Glioblastoma Multiforme (GBM) continues to have a poor patient prognosis despite
      optimal standard of care. Glioma stem cells (GSCs) have been implicated as the
      presumed cause of tumor recurrence and resistance to therapy. With this in mind,
      we screened a diverse chemical library of 2,000 compounds to identify therapeutic
      agents that inhibit GSC proliferation and therefore have the potential to extend
      patient survival. High-throughput screens (HTS) identified 78 compounds that
      repeatedly inhibited cellular proliferation, of which 47 are clinically approved
      for other indications and 31 are experimental drugs. Several compounds (such as
      digitoxin, deguelin, patulin and phenethyl caffeate) exhibited high cytotoxicity,
      with half maximal inhibitory concentrations (IC50) in the low nanomolar range. In
      particular, the FDA approved drug for the treatment of alcoholism, disulfiram
      (DSF), was significantly potent across multiple patient samples (IC50 of 31.1
      nM). The activity of DSF was potentiated by copper (Cu), which markedly increased
      GSC death. DSF-Cu inhibited the chymotrypsin-like proteasomal activity in
      cultured GSCs, consistent with inactivation of the ubiquitin-proteasome pathway
      and the subsequent induction of tumor cell death. Given that DSF is a relatively
      non-toxic drug that can penetrate the blood-brain barrier, we suggest that DSF
      should be tested (as either a monotherapy or as an adjuvant) in pre-clinical
      models of human GBM. Data also support targeting of the ubiquitin-proteasome
      pathway as a therapeutic approach in the treatment of GBM.

PMID- 23165411
TI  - Symbol Digit Modalities Test: normative values for Spanish home care residents: a
      pilot study.
AB  - INTRODUCTION: The Symbol Digit Modalities Test (SDMT) is a widely used test for
      the evaluation of neurological disorders. Normative data have been published for
      this test in different populations, however there are no values regarding elderly
      persons residing in geriatric homes. This study has aimed to apply the SDMT on a
      sample made up of Spanish elderly people living in geriatrics home care residents
      to obtain normative values, considering gender, age and education level.
      METHODOLOGY: The standard pen and paper version of the SDMT was administered to
      821 home care residents older than 55 years. Information regarding age, gender
      and education was obtained by means of personal health records provided by each
      institution. A descriptive analysis was made to generate tables including
      normative data. The final values were adjusted based on age and educational level
      of the participants and presented in weighted scales. RESULTS: The SDMT was
      filled out by 321 participants. Final distribution of the sample made it possible
      to calculate normative values based on age. A negative correlation was observed
      between the SDMT mean score and age of the participants while education
      significantly affected the results obtained. CONCLUSIONS: The SDMT normative data
      obtained after the application of the SDMT in the elderly living in home care
      residents were found to be strongly influenced by age and education. Use of the
      oral version is recommended for future studies of this kind.

PMID- 23165412
TI  - Agomelatine in elderly--finally a patient friendly antidepressant in
      psychogeriatry?
AB  - BACKGROUND: Geriatric depression is a serious psychiatric conditions with
      prevalence from 10-40% in community living seniors. Polymorbidity and potential
      vulnerability of seniors towards medication is a challenge for seeking newer,
      well tolerated antidepressant with good clinical efficiency and safety.
      Agomelatine is new promising antidepressant which could fulfill these criteria.
      OBJECTIVE: Evaluation of effectiveness, safety and side effects of agomelatine
      used for treatment senior patients with major depression hospitalized in
      inpatient psychogeriatric ward in Mental hospital in Kromeriz (2010-2011).
      METHODS: Psychiatric scales Montgomery-Asberg Depression Scale (MADRS) and
      Clinical Global Impression (CGI) were used initially before starting with
      agomelatine treatment, then after 4 and 8 weeks and finally after 12 weeks of
      using agomelatine. Potential side effects caused by agomelatine (side effects
      according AISL databasis--Automatized Information system of Registered Drugs in
      the Czech republic) were monitored after 12 weeks of treatment with agomelatine.
      RESULTS: While treating major depression in seniors with agomelatine, decrease in
      Montgomery-Asberg Depression Scale (MADRS), Clinical Global Impression scale
      (CGI) was evident after 4 weeks of treatment and continued constantly after 8 and
      12 weeks of treatment. Clinical remission was achieved in all studied patients.
      CONCLUSION: Agomelatine proved excellent efficiency in treating severe major
      depression in seniors with no serious averse effects.

PMID- 23165413
TI  - Cyber-Neuropsychology: application of new technologies in neuropsychological
      evaluation.
AB  - Neuropsychological evaluation deals with the study of cerebral functioning
      through the persons' performance. It makes it possible to collaborate the
      clinical diagnosis and to provide information on deficit and skills. Specialized
      care in rural environments is uncommon, and often means impossibility to access
      some services. This study has aimed to evaluate the possibility of using
      neuropsychological evaluation by internet videoconferences. Our research was
      based on the traditional and online application of the SCIP-S to 30 subjects who
      were diagnosed with schizophrenia. The 30 subjects were randomly divided into two
      groups (Group A and B). Both groups underwent the two conditions inversely. The
      results show some differences and similarities when the results in both types of
      applications SCIP-S are compared. In conclusion, cyber-neuropsychology is
      possible and may be a complement and alternative to traditional assessment when
      they cannot develop.

PMID- 23165414
TI  - Effects of temperament and emotion regulation styles in determining negative
      emotional states.
AB  - INTRODUCTION: The interplay of reactive and regulatory temperamental processes
      appears to be essential for a better understanding of emotional states and
      disorders. In this study we explored the prospective relationship between
      reactive temperament (negative affect), regulatory temperament (effortful
      control), negative emotion regulation styles (rumination and suppression) and
      self-recorded anxiety, worry, and avoidance in naturalistic conditions. METHOD:
      Thirty-two young adults were first assessed through questionnaires on negative
      affectivity, effortful control, and two forms of negative emotion regulation
      (rumination and suppression). After this they recorded anxiety, worry, and
      avoidance three times a day over 50 consecutive days through an on-line access
      electronic diary. RESULTS: High levels of negative affect and low levels of
      effortful control were associated with higher levels of anxiety, worry, and
      avoidance (p<.01). The prospective association between negative affectivity and
      avoidance was moderated by effortful control (Total R(2)=.49). Moreover, the
      brooding facet of rumination totally mediated the association between negative
      affect and anxiety with a significant indirect effect (Effect=.30, Boot CI95%=.09
      to .69). CONCLUSIONS: Avoidance patterns are significantly determined by negative
      affect--effortful control interaction and rumination, especially brooding,
      totally mediates the relationship between negative affect and anxiety.

PMID- 23165415
TI  - Community alternatives to acute inpatient care for severe psychiatric patients.
AB  - OBJECTIVES: Community psychiatry has mainly relied upon intermediate long term
      care services while there is a large gap between patient's needs and availability
      of acute care services. Taking this into consideration, the main aim of this
      paper is to review the evidence supporting the efficacy and feasibility of
      implementing the new models of care developed to fulfil the gap in the provision
      of community and hospital care for acute and severely ill patients. Finally the
      paper will propose a "care balanced approach" to integrate the key elements of
      the new alternatives of acute community and hospital care in the mental health
      system. MATERIAL AND METHOD: A review of the current literature was used to
      identify the key components of acute care for psychiatric illness. For this
      purpose Medline (1966-2010), EMBASE (1980-2010), and PsycINFO (1985-2010)
      databases were reviewed using key terms relating to assertive outreach, home
      treatment/crisis resolution, psychiatric acute day care, deinstitutionalization,
      Mental Health Service Models. RESULTS: Three main types of acute care have been
      identified: Acute Continuous Day Care (ACDC) -day hospitals -, Assertive Outreach
      Care (AOC) -Assertive Community and Assertive Outreach teams-, and Home Acute
      Care (HAC) -Crisis resolution, Home treatment teams-. The feasibility of these
      alternatives is supported by available evidence. Although these acute care
      alternatives may be complementary and could be combined for achieving a greater
      positive impact on the clinical and social recovery of the patients, there are
      usually implemented independently. CONCLUSIONS: An integrative acute care
      subsystem combining these three strategies in a balanced care system should be
      formally incorporated to the advanced community model in mental health care.

PMID- 23165416
TI  - Clinical and epidemiological aspects of suicide in patients with schizophrenia.
AB  - Suicide is a major cause of death among patients with schizophrenia. Suicide
      phenomenon's characterization is the best available approach for improved
      prediction and prevention of suicide. Patients at high risk for suicide need a
      more intensive monitoring and intervention. The aim of this review is to
      characterize, from a clinical-epidemiological point of view, the phenomenon of
      completed suicide in schizophrenia. We performed a systematic review to identify
      the most relevant studies published between 1994 and 2009, by searching on the
      international database Medline and among previous reviews references. Patients
      with schizophrenia experience higher mortality rates than the general population,
      especially due to the suicide. Most patients with schizophrenia who commit
      suicide are likely to be young and males, with a higher risk around illness onset
      and hospitalization periods. Previous suicide attempts are an important risk
      factor for completed suicide. Suicide risk is associated to psychotic positive
      symptoms, affective symptoms, depression and substance abuse. Treatment adherence
      is as protective factor. Patients with schizophrenia are likely to commit suicide
      by violent means. Suicide prevention should focus on treating affective symptoms
      and syndromes, improving treatment compliance and providing intensive monitoring
      to those patients at high risk of suicide, specially around hospitalization
      periods. Further studies are needed to clarify differential characteristics
      between suicide behaviour and completed suicide.

PMID- 23165417
TI  - Concurrence of multiples factors in the occurrence of ventricular arrhythmia in
      patient treated with aripiprazole.
AB  - INTRODUCTION: The Importance of the cardiovascular effects, fundamentally the
      ventricular arrhythmias, produced by the antipsychotic ones, is discussed.
      CLINICAL CASE: 28 year old patient with morbid obesity, operated by bariatric
      surgery, with good result, suffers a ventricular no supported polymorphic
      tachycardia while he was heightening treatment with aripiprazole and fluoxetine.
      CONCLUSIONS: To value the influence of diverse factors for the production of
      ventricular arrhythmias emphasizing fundamentally the interactions of
      aripiprazole and the loss of weight.

PMID- 23165418
TI  - Combustion resistance of the 129Xe hyperpolarized nuclear spin state.
AB  - Using a methane-xenon mixture for spin exchange optical pumping, MRI of
      combustion was enabled. The (129)Xe hyperpolarized nuclear spin state was found
      to sufficiently survive the complete passage through the harsh environment of the
      reaction zone. A velocity profile (V(z)(z)) of a flame was recorded to
      demonstrate the feasibility of MRI velocimetry of transport processes in
      combustors.

PMID- 23165421
TI  - Prospects for hydrogen storage in graphene.
AB  - Hydrogen-based fuel cells are promising solutions for the efficient and clean
      delivery of electricity. Since hydrogen is an energy carrier, a key step for the
      development of a reliable hydrogen-based technology requires solving the issue of
      storage and transport of hydrogen. Several proposals based on the design of
      advanced materials such as metal hydrides and carbon structures have been made to
      overcome the limitations of the conventional solution of compressing or
      liquefying hydrogen in tanks. Nevertheless none of these systems are currently
      offering the required performances in terms of hydrogen storage capacity and
      control of adsorption/desorption processes. Therefore the problem of hydrogen
      storage remains so far unsolved and it continues to represent a significant
      bottleneck to the advancement and proliferation of fuel cell and hydrogen
      technologies. Recently, however, several studies on graphene, the one-atom-thick
      membrane of carbon atoms packed in a honeycomb lattice, have highlighted the
      potentialities of this material for hydrogen storage and raise new hopes for the
      development of an efficient solid-state hydrogen storage device. Here we review
      on-going efforts and studies on functionalized and nanostructured graphene for
      hydrogen storage and suggest possible developments for efficient storage/release
      of hydrogen under ambient conditions.

PMID- 23165420
TI  - Autoantibodies against insulin-like growth factor-binding protein-2 as a
      serological biomarker in the diagnosis of lung cancer.
AB  - Insulin-like growth factor-binding protein-2 (IGFBP-2) is considered to be a
      human tumor antigen, and the tumor-specific immunity of IGFBP-2 has been reported
      in several types of cancer. The purpose of this study was to evaluate whether
      autoantibodies to IGFBP-2 can be used as diagnostic markers in lung cancer. The
      results demonstrated that serum anti-IGFBP-2 autoantibody levels were
      significantly elevated in lung cancer (mean, 1,633.318 ng/ml; median, 1,651.462
      ng/ml; range, 342.732-4932.582 ng/ml) compared with benign lung disease
      (1,210.139, 1,035.900, 547.596-2,331.167 ng/ml) and normal controls (1,303.369,
      1,194.800, 528.200-2140.500 ng/ml). The sensitivity and specificity of anti-IGFBP
      2 autoantibodies in diagnosing lung cancer was 73.2 and 60.6%, respectively. When
      serum IGFBP-2 and anti-IGFBP-2 autoantibody were used together in the diagnosis
      of lung cancer, it can increase the discriminative power for lung cancer with a
      sensitivity of 85.7% and a specificity of 57.5%. In conclusion, this study
      demonstrates that circulating anti-IGFBP-2 autoantibodies can be used as a
      potential biomarker in diagnosing lung cancer.

PMID- 23165422
TI  - Integration of clinical and patient-reported outcomes in surgical oncology.
AB  - BACKGROUND: Patient-reported outcomes (PROs) provide information about the
      patient perspective and experience of undergoing surgery for cancer, but evidence
      suggests that they are not used widely to influence practice. This review
      considers key challenges and opportunities for using PROs effectively in
      gastrointestinal surgical oncology, drawing on principles learnt from surgical
      oncology in general. METHODS: Systematic reviews of randomized controlled trials
      (RCTs) in surgical oncology reporting PROs as primary or secondary outcomes, and
      studies examining methods to communicate PRO information, were identified. Common
      themes are summarized and the future of PRO studies considered. RESULTS: Reviews
      highlighted the need for improved design, conduct and reporting of PROs in RCTs
      in surgical oncology. Main issues related to the multiplicity of PRO measures
      hindering data synthesis and clinical understanding, problems with missing data
      risking bias, and limited integration of clinical and PRO data undermining the
      role of PRO data in practice. Reviews indicated that patients want PRO data to
      meet information needs and early work shows that graphically displayed PROs are
      understood by patients. CONCLUSION: PROs have a role in the evaluation of
      surgical oncology, but increased consensus and collaboration between surgeons and
      methodologists is needed to improve the design, conduct and reporting of PROs
      with clinical outcomes in trials. Possible solutions include investing more
      effort and systematic thought into the PRO rationale in RCTs, the development and
      use of 'core outcome sets' with PROs, and implementation of the extension to the
      Consolidated Standards of Reporting Trials (CONSORT) guidelines for reporting
      PROs in RCTs.

PMID- 23165423
TI  - Cell type specific interleukin-6 induced responses in tumor keratinocytes and
      stromal fibroblasts are essential for invasive growth.
AB  - Interleukin-6 (IL-6) is one of the major inflammatory interleukins that has been
      linked to cancer progression. In our model for human skin squamous cell carcinoma
      (SCC), IL-6 expression is strongly upregulated upon progression from benign
      tumors to highly malignant, metastasizing SCCs. We now demonstrate that IL-6
      promotes malignant and invasive tumor growth in human skin SCCs by inducing cell
      type specific cytokine profiles in tumor keratinocytes and stromal fibroblasts,
      activating the latter towards a tumor associated fibroblast (TAF) phenotype. In
      three-dimensional organotypic cocultures in vitro invasive growth of IL-6
      overexpressing tumor keratinocytes, is associated with increased expression of
      matrix metalloproteinase-2 (MMP-2), MMP-14 and tissue inhibitor of
      metalloproteinases-2, and clearly depends on IL-6 activated fibroblasts. IL-6
      induced secretion of monocyte chemotactic protein-1 (MCP-1) in tumor
      keratinocytes and of hepatocyte growth factor in fibroblasts is crucial for
      regulating expression and activation of MMP-2. This functional role of IL-6 is
      confirmed in vivo. Here MMP-14 and MMP-2 expression occur exclusively in surface
      transplants of IL-6 overexpressing keratinocytes and fibroblasts are identified
      as important source of MMP-2. Our data indicate that tumor keratinocytes derived
      IL-6 activates stromal fibroblasts towards a TAF phenotype, promoting tumor
      invasion via enhanced expression and activation of MMP-2. 

PMID- 23165424
TI  - Silencing the expression of connexin 43 decreases inflammation and joint
      destruction in experimental arthritis.
AB  - The objective of the present study was to determine whether the expression of
      connexin 43 (Cx43) effected on inflammatory conditions in rat fibroblast-like
      synoviocytes (FLS) and on rat model of rheumatoid arthritis (RA). The expression
      of Cx43 in rat FLS stimulated with lipopolysaccharide (LPS) was confirmed by real
      time reverse transcriptase polymerase chain reaction (RT-PCR). The effects of
      small-interfering RNA targeting Cx43 (siCx43) on pro-inflammatory cytokines and
      chemokine were assessed by real-time RT-PCR and enzyme-linked immunosorbent assay
      (ELISA). The therapeutic and side effects of siCx43 in a rat model of collagen
      induced arthritis (CIA) were examined by in vivo electroporation method. LPS
      markedly enhanced Cx43 gene expression in rat FLS, with transfection of siCx43
      suppressing the over-expression of pro-inflammatory cytokines and the chemokine.
      Treatment of CIA rats with siCx43 significantly ameliorated paw swelling, and
      significantly reduced histological arthritis scores and radiographic scores. In
      histological appearance of rat ankle joints, siCx43 treatment significantly
      decreased the number of tartrate-resistant acid phosphatase (TRAP)-positive
      (osteoclast-like) cells. These findings indicated that siCx43 had anti
      inflammatory effects in rat FLS and efficiently inhibited the development of CIA.
      Cx43 may play an important role in the pathophysiology of RA, and may be a
      potential target molecule for novel RA therapies.

PMID- 23165425
TI  - With a little help from my friends.

PMID- 23165426
TI  - Safety of osteoanabolic therapy: a decade of experience.

PMID- 23165427
TI  - An ELIXIR for bone loss?

PMID- 23165429
TI  - Effect of solution conductivity and electrode shape on the deposition of carbon
      nanotubes from solution using dielectrophoresis.
AB  - Dielectrophoresis (DEP) is a popular technique for fabricating carbon nanotube
      (CNT) devices. The electric current passing through the solution during DEP
      creates a temperature gradient, which results in electrothermal fluid flow
      because of the presence of the electric field. CNT solutions prepared with
      various methods can have different conductivities and the motion of the solution
      because of the electrothermal phenomenon can affect the DEP deposition
      differently in each case. We investigated the effect of this movement in
      solutions with various levels of conductivity through experiments as well as
      numerical modeling. Our results show that electrothermal motion in the solution
      can alter the deposition pattern of the nanotubes drastically for high
      conductivity solutions, while DEP remains the dominant force when a low
      conductivity (surfactant-free) solution is used. The extent of effectiveness of
      each force is discussed in the various cases and the fluid movement model is
      investigated using two- and three-dimensional finite element simulations.

PMID- 23165428
TI  - The psychosis high-risk state: a comprehensive state-of-the-art review.
AB  - CONTEXT: During the past 2 decades, a major transition in the clinical
      characterization of psychotic disorders has occurred. The construct of a clinical
      high-risk (HR) state for psychosis has evolved to capture the prepsychotic phase,
      describing people presenting with potentially prodromal symptoms. The importance
      of this HR state has been increasingly recognized to such an extent that a new
      syndrome is being considered as a diagnostic category in the DSM-5. OBJECTIVE: To
      reframe the HR state in a comprehensive state-of-the-art review on the progress
      that has been made while also recognizing the challenges that remain. DATA
      SOURCES: Available HR research of the past 20 years from PubMed, books, meetings,
      abstracts, and international conferences. STUDY SELECTION AND DATA EXTRACTION:
      Critical review of HR studies addressing historical development, inclusion
      criteria, epidemiologic research, transition criteria, outcomes, clinical and
      functional characteristics, neurocognition, neuroimaging, predictors of psychosis
      development, treatment trials, socioeconomic aspects, nosography, and future
      challenges in the field. DATA SYNTHESIS: Relevant articles retrieved in the
      literature search were discussed by a large group of leading worldwide experts in
      the field. The core results are presented after consensus and are summarized in
      illustrative tables and figures. CONCLUSIONS: The relatively new field of HR
      research in psychosis is exciting. It has the potential to shed light on the
      development of major psychotic disorders and to alter their course. It also
      provides a rationale for service provision to those in need of help who could not
      previously access it and the possibility of changing trajectories for those with
      vulnerability to psychotic illnesses.

PMID- 23165430
TI  - Association between DNA methylation of HSPB1 and death in low Gleason score
      prostate cancer.
AB  - BACKGROUND: Heat shock protein 27 (Hsp-27) encoded by gene HSPB1 is a critical
      regulator of the behavioral phenotype of human prostate cancer (PCa) cells,
      enhanced expression being associated with highly aggressive disease and poor
      clinical outcome. In contrast, the protein is not expressed in PCas of low
      malignant potential. To gain insight into the mechanism regulating its
      expression, we tested the hypothesis that differential methylation of CpG islands
      within HSPB1 controls transcription and subsequent translation of the gene.
      METHODS: We studied prostate epithelial cell lines and tissue biopsies, including
      59 BPH and 415 PCas, of which 367 were a cohort of men with up to 20 years of
      follow-up. Methylation across the gene (DNA methylation (DNAme)) was assayed by
      pyrosequencing. Hsp-27 expression was assessed by western blot and
      immunohistochemistry. RESULTS: In cancer tissues, methylation increased in a 3'
      direction (P < 0.0001) whereas in benign hyperplasia methylation was constantly
      below 5%, a cutoff giving a specificity of 100% and sensitivity of 50%. Although
      methylation of the promoter region was significantly discriminating between
      benign and malignant prostatic epithelia, it compared poorly with methylation of
      the first intron. The prognostic value of HSPB1 DNAme was confirmed by both
      univariate (hazard ratio 1.77 per 50% increment, P = 0.02) and multivariate
      models. Interaction between HSPB1 methylation and Gleason score revealed high
      DNAme to be a reliable prognostic marker of poor outcome in men with low Gleason
      score (P = 0.014). CONCLUSIONS: Our data indicate CpG methylation of the first
      HSPB1 intron to be an important biomarker that identifies aggressive PCas
      otherwise regarded as low risk by current clinical criteria but that,
      biologically, require immediate active management.

PMID- 23165431
TI  - Metabolic syndrome and lower urinary tract symptoms: the role of inflammation.
AB  - BACKGROUND: Epidemiological data indicate that lower urinary tract symptoms
      (LUTS)/BPH can be associated with metabolic syndrome (MetS). Chronic inflammation
      has been proposed as a candidate mechanism at the crossroad between these two
      clinical entities.Aim of study is to examine the correlation among pre-operatory
      LUTS/BPH severity, MetS features and inflammatory infiltrates in prostatectomy
      specimens. METHODS: A total of 271 consecutive men treated with simple
      prostatectomy were retrospectively selected for this study in two tertiary
      referral centers for LUTS/BPH. Prostate diameters and volume were measured by
      transrectal ultrasound, LUTS scored by International Prostate Symptom Score
      (IPSS) and obstruction by uroflowmetry. The International Diabetes Federation and
      American Heart Association and the National Heart, Lung and Blood Institute was
      used to define MetS. The inflammatory infiltrate was investigated combining
      anatomic location, grade and extent of flogosis into the overall inflammatory
      score (IS); the glandular disruption (GD) was used as a further marker. RESULTS:
      Eighty-six (31.7%) men were affected by MetS. Prostatic volume and anterior
      posterior (AP) diameter were positively associated to the number of MetS
      components. Among MetS determinants, only dyslipidaemia (increased serum
      triglycerides and reduced serum high-density lipoprotein) was associated with an
      increased risk of having a prostatic volume >60 cm(3) (hazard ratio (HR) = 3.268,
      P < 0.001). A significant positive correlation between the presence of MetS and
      the IS was observed. MetS patients presented lower uroflowmetric parameters as
      compared with those without MetS (Maximum flow rate (Q(max)): 8.6 vs 10.1, P =
      0.008 and average flow rate (Q(ave)): 4.6 vs 5.3, P = 0.033, respectively), and
      higher obstructive urinary symptoms score (P = 0.064). A positive correlation
      among both IS-GD and IPSS Score was also observed (adjusted r = 0.172, P = 0.008
      and adjusted r = 0.128, P = 0.050). CONCLUSIONS: MetS is associated with prostate
      volume, prostatic AP diameter and intraprostatic IS. The significantly positive
      association between MetS and prostatic AP diameter could support the observation
      that MetS patients presented lower uroflowmetric parameters. In conclusion, MetS
      can be regarded as a new determinant of prostate inflammation and BPH
      progression.

PMID- 23165433
TI  - Structural, magnetic and optical properties of an Fe(III) dimer bridged by the
      meridional planar divergent N,N'-bis(salicyl)hydrazide and its photo- and electro
      chemistry in solution.
AB  - {Fe(III)Cl(DMF)(2)}(2)(L) where L is N,N'-bis(salicyl)hydrazide has been
      synthesized as red crystals and characterized using single-crystal diffraction,
      infrared and UV-vis spectroscopies, and its magnetic properties studied. The
      dimeric unit in the structure is formed through the two meridional sets of
      divergent O, N, O coordinating atoms of the hexacoordinated and quadruply charged
      ligand. With the presence of the inversion symmetry the Fe atoms are strictly
      planar with the ligand. The magnetic exchange interaction is found to be
      antiferromagnetic with a J = -5.98(3) cm(-1) through the rare Fe-N-N-Fe pathway.
      Irradiation of the FeCl(3)/H(4)L red DMF solution in the visible region of the
      spectrum resulted in its complete discoloration and from which the unknown
      colorless salt [Fe(II)(DMF)(6)][Fe(II)Cl(4)] and the neutral ligand have been
      identified by single crystal diffraction. The UV-visible spectra of FeCl(3),
      H(4)L and their mixture in DMF solution indicate that the iron complex is the
      absorbing species and the presence of the free ligand in the irradiated solution
      suggests that the ligand is potentially acting as a catalyst to the
      photoreduction of Fe(III) to Fe(II), while electrochemistry points to a mixed
      valent (Fe(II)-Fe(III)) intermediate in the process.

PMID- 23165435
TI  - Prevention of chemotherapy-induced nausea and vomiting and the role of neurokinin
      1 inhibitors:  from guidelines to clinical practice in solid tumors.
AB  - A significant proportion of cancer patients experience nausea or vomiting during
      the course of their disease, either because of the cancer itself or because of
      the treatment received. Highly or moderately emetogenic drugs are part of the
      standard chemotherapy regimens frequently used in patients with lung cancer,
      breast cancer, ovarian cancer, and several other common solid tumors. In this
      review, we describe the impact of nausea and vomiting in patients receiving
      chemotherapy, and the main progress achieved in the prophylaxis of chemotherapy
      induced nausea and vomiting with the introduction of neurokinin 1 inhibitors. The
      adherence to existing guidelines is particularly important to avoid suboptimal
      prophylaxis and maximize patients' outcome. This review is focused on lung,
      breast, ovarian, and colorectal cancer, which are among the solid tumors
      characterized by a numeric and clinical relevance of the chemotherapy-induced
      nausea and vomiting issue because of the wide use of highly and/or moderately
      emetogenic chemotherapy regimens.

PMID- 23165440
TI  - Self-decarboxylation of trichloroacetic acid redox catalyzed by trichloroacetate
      ions in acetonitrile solutions.
AB  - In mixtures of trichloroacetate ion and trichloroacetic acid in acetonitrile,
      trichloromethyl radicals are produced as a result of the redox reaction between
      the acid and its conjugate base. The reaction follows a loop mechanism in which
      the trichloroacetic acid is slowly consumed by proton reduction while the
      trichloroacetate ion is oxidized like in an electrochemical Kolbe reaction. The
      hydroquinone-trichloroacetate complex was a good sensor of this unexpected self
      decarboxylation redox reaction.

PMID- 23165441
TI  - Exploiting the mTOR paradox for disease prevention.

PMID- 23165442
TI  - Assessment of contrast-enhanced computed tomography for imaging of cartilage
      during fracture healing.
AB  - Assessment of the early stages of fracture healing via X-rays and computed
      tomography is limited by the low radio-opacity of cartilage. We validated a
      method of contrast-enhanced computed tomography (CECT) for non-destructive
      identification of cartilage within a healing fracture callus. Closed, stabilized
      fractures in femora of C57BL/6 mice were harvested on post-operative day 9.5 and
      imaged ex vivo with micro-computed tomography (uCT) before and after incubation
      in a cationic contrast agent that preferentially accumulates in cartilage due to
      the high concentration of sulfated glycosaminoglycans in the tissue. Co
      registration of the pre- and post-incubation images, followed by image
      subtraction, enabled two- and three-dimensional delineation of mineralized
      tissue, soft callus, and cartilage. The areas of cartilage and callus identified
      with CECT were compared to those identified with the gold-standard method of
      histomorphometry. No difference was found between the areas of cartilage measured
      by the two methods (p = 0.999). Callus area measured by CECT was smaller than,
      but strongly predictive of (R(2) = 0.80, p < 0.001), the corresponding
      histomorphometric measurements. CECT also enabled qualitative identification of
      mineralized cartilage. These findings indicate that the CECT method provides
      accurate, quantitative, and non-destructive visualization of the shape and
      composition of the fracture callus, even during the early stages of repair when
      little mineralized tissue is present. The non-destructive nature of this method
      would allow subsequent analyses, such as mechanical testing, to be performed on
      the callus, thus enabling higher-throughput, comprehensive investigations of bone
      healing.

PMID- 23165444
TI  - Assembly of alternating spin-chains with magnetically anisotropic cobalt(II)
      dimers.
AB  - A dimeric carboxylato complex of cobalt(II), [Co(2)(II)(1,2-chedc)(2)(Im)(2)] (1)
      (1,2-chedc = cyclohex-1-ene-1,2-dicarboxylate and Im = imidazole), has been
      isolated. This complex can be further linked by chloro- or carboxylato-ligands,
      affording respectively one-dimensional chain structures of
      (1)(infinity)[Co(2)(II)(MU-Cl)(2)(1,2-chedc)(Im)(2)] (2) and
      (1)(infinity)[Co(II)(1,2-chedc)(Im)] (3). Compound 1 shows weak antiferromagnetic
      interactions passing through the body of the dicarboxylate as well as substantial
      single-ion magnetic anisotropy (zero-field splitting energy Delta = 8.5 cm(-1)).
      Both 2 and 3 exhibit typical alternating spin-chain behaviour in the higher
      temperature region, but they display disparate behaviours at lower temperatures.
      For 2, alternating F-AF interactions compete (J(1) = 6.7 K and J(2) = -8.2 K),
      resulting in paramagnet-like behaviour with no clear evidence of three
      dimensional contact. Compound 3 exhibits stronger intrachain AF-AF exchange
      coupling interactions (J(1) = -9.3 K and J(2) = -4.3 K), leading to non
      diamagnetic ground state due to the tiling of adjacent spins. Long-range magnetic
      ordering was observed below 10 K. Its narrow hysteresis loop suggests the use of
      3 as a soft magnet.

PMID- 23165443
TI  - Protein kinase B/AKT isoform 2 drives migration of human mesenchymal stem cells.
AB  - This study was designed to investigate the migratory behavior of adult human
      mesenchymal stem cells (MSC) and the underlying mechanism. Cell migration was
      assessed by transwell, wound healing and time-lapse in vivo motility assays.
      Pharmacological inhibitors were used to determine the potential mechanism
      responsible for cell migration and invasion. The tests that were implemented
      revealed that MSC were fairly migratory. Protein kinase B (AKT) was strongly
      activated at the basal level. Through our analyses we demonstrated that
      pharmacological inactivation of AKT2 but not AKT1 significantly decreased cell
      migration and invasion. Although preliminary, collectively our results indicate
      that AKT2 activation plays a critical role in enabling MSC migration.

PMID- 23165446
TI  - Contemporary perioperative care strategies.
AB  - BACKGROUND: Historically, the preoperative and postoperative care of patients
      with gastrointestinal cancer was provided by surgeons. Contemporary perioperative
      care is a truly multidisciplinary endeavour with implications for cancer-specific
      outcomes. METHODS: A literature review was performed querying PubMed and the
      Cochrane Library for articles published between 1966 to 2012 on specific
      perioperative interventions with the potential to improve the outcomes of
      surgical oncology patients. Keywords used were: fast-track, enhanced recovery,
      accelerated rehabilitation, multimodal and perioperative care. Specific
      interventions included normothermia, hyperoxygenation, surgical-site infection,
      skin preparation, transfusion, non-steroidal anti-inflammatory drugs,
      thromboembolism and antibiotic prophylaxis, laparoscopy, radiotherapy,
      perioperative steroids and monoclonal antibodies. Included articles had to be
      randomized controlled trials, prospective or nationwide series, or systematic
      reviews/meta-analyses, published in English, French or German. RESULTS: Important
      elements of modern perioperative care that improve recovery of patients and
      outcomes in surgical oncology include accelerated recovery pathways,
      thromboembolism and antibiotic prophylaxis, hyperoxygenation, maintenance of
      normothermia, avoidance of blood transfusion and cautious use of non-steroidal
      anti-inflammatory drugs, promotion of laparoscopic surgery, chlorhexidine-alcohol
      skin preparation and multidisciplinary meetings to determine multimodal therapy.
      CONCLUSION: Multidisciplinary management of perioperative patient care has
      improved outcomes.

PMID- 23165447
TI  - Use of multivariate analysis to suggest a new molecular classification of
      colorectal cancer.
AB  - Molecular classification of colorectal cancer (CRC) is currently based on
      microsatellite instability (MSI), KRAS or BRAF mutation and, occasionally,
      chromosomal instability (CIN). Whilst useful, these categories may not fully
      represent the underlying molecular subgroups. We screened 906 stage II/III CRCs
      from the VICTOR clinical trial for somatic mutations. Multivariate analyses
      (logistic regression, clustering, Bayesian networks) identified the primary
      molecular associations. Positive associations occurred between: CIN and TP53
      mutation; MSI and BRAF mutation; and KRAS and PIK3CA mutations. Negative
      associations occurred between: MSI and CIN; MSI and NRAS mutation; and KRAS
      mutation, and each of NRAS, TP53 and BRAF mutations. Some complex relationships
      were elucidated: KRAS and TP53 mutations had both a direct negative association
      and a weaker, confounding, positive association via TP53-CIN-MSI-BRAF-KRAS. Our
      results suggested a new molecular classification of CRCs: (1) MSI(+) and/or BRAF
      mutant; (2) CIN(+) and/or TP53(-) mutant, with wild-type KRAS and PIK3CA; (3)
      KRAS- and/or PIK3CA-mutant, CIN(+) , TP53-wild-type; (4) KRAS(-) and/or PIK3CA
      mutant, CIN(-) , TP53-wild-type; (5) NRAS-mutant; (6) no mutations; (7) others.
      As expected, group 1 cancers were mostly proximal and poorly differentiated,
      usually occurring in women. Unexpectedly, two different types of CIN(+) CRC were
      found: group 2 cancers were usually distal and occurred in men, whereas group 3
      showed neither of these associations but were of higher stage. CIN(+) cancers
      have conventionally been associated with all three of these variables, because
      they have been tested en masse. Our classification also showed potentially
      improved prognostic capabilities, with group 3, and possibly group 1,
      independently predicting disease-free survival.

PMID- 23165448
TI  - Decreasing colectomy rates for ulcerative colitis: a population-based time trend
      study.
AB  - OBJECTIVES: Colectomy rates for ulcerative colitis (UC) have been inconsistently
      reported. We assessed temporal trends of colectomy rates for UC, stratified by
      emergent vs. elective colectomy indication. METHODS: From 1997 to 2009, we
      identified adults hospitalized for a flare of UC. Medical charts were reviewed.
      Temporal changes were evaluated using linear regression models to estimate the
      average annual percent change (AAPC) in surgical rates. Logistic regression
      analysis compared: (i) UC patients responding to medical management in hospital
      to those who underwent colectomy; (ii) UC patients who underwent an emergent vs.
      elective colectomy; and (iii) temporal trends of drug utilization. RESULTS: From
      1997 to 2009, colectomy rates significantly dropped for elective colectomies with
      an AAPC of -7.4% (95% confidence interval (CI): -10.8%, -3.9%). The rate of
      emergent colectomies remained stable with an AAPC of -1.4% (95% CI: -4.8%, 2.0%).
      Azathioprine/6-mercaptopurine prescriptions increased from 1997 to 2009 (odds
      ratio (OR)=1.15; 95% CI: 1.09-1.22) and infliximab use increased after 2005
      (OR=1.68; 95% CI: 1.25-2.26). A 13% per year risk adjusted reduction in the odds
      of colectomy (OR=0.87; 95% CI: 0.83-0.92) was observed in UC patients responding
      to medical management compared with those who required colectomy. Emergent
      colectomy patients had a shorter duration of flare (<2 weeks vs. 2-8 weeks,
      OR=5.31; 95% CI: 1.58-17.81) and underwent colectomy early after diagnosis (<1
      year vs. 1-3 years, OR=5.48; 95% CI: 2.18-13.79). CONCLUSIONS: From 1997 to 2009,
      use of purine anti-metabolites increased and elective colectomy rates in UC
      patients decreased significantly. In contrast, emergent colectomy rates were
      stable, which may have been due to rapid progression of disease activity.

PMID- 23165449
TI  - Expression of NO synthases and redox enzymes in umbilical arteries from newborns
      born small, appropriate, and large for gestational age.
AB  - BACKGROUND: Modified expression of nitric oxide synthases (NOSs) and an imbalance
      between the pro-oxidative and the antioxidative system accompany endothelial
      dysfunction, the first stage of atherosclerosis. Humans born small (SGA) or large
      (LGA) for gestational age are at higher risk of developing atherosclerosis later
      in life than humans born appropriate for gestational age (AGA). We hypothesized
      that indicators of endothelial dysfunction could be detectable at birth. The
      purpose of this study was to find out whether the expression patterns of NO
      synthases (endothelial NOS (eNOS), inducible NOS (iNOS), and neuronal NOS
      (nNOS)), pro-oxidative enzymes (components of nicotinamide adenine dinucleotide
      phosphate (NADPH) oxidases, NADPH oxidase 1 (NOX1), NOX2, NOX4, p22phox, and
      p47phox), and antioxidative enzymes (superoxide dismutase 1-3 (SOD1-3),
      glutathione peroxidase 1 (GPX1), and catalase) in umbilical arteries differ among
      SGA, LGA, and AGA newborns. METHODS: Thirty-six umbilical cords were obtained
      from healthy, normal, full-term SGA, AGA, and LGA newborns. The umbilical
      arteries were dissected and homogenized. mRNA expression was analyzed with
      quantitative real-time PCR. Western blotting was performed to determine protein
      expression. RESULTS: mRNA and protein expression of NO synthases, pro-oxidative
      enzymes, and antioxidative enzymes did not differ in the umbilical arteries from
      newborns of the three groups. CONCLUSION: Indicators of endothelial dysfunction
      in terms of differences in enzyme expression in SGA or LGA newborns vs. AGA
      newborns were not present at birth.

PMID- 23165450
TI  - CD4+ T-cell counts and interleukin-8 and CCL-5 plasma concentrations discriminate
      disease severity in children with RSV infection.
AB  - BACKGROUND: Current tools to predict the severity of respiratory syncytial virus
      (RSV) infection might be improved by including immunological parameters. We
      hypothesized that a combination of inflammatory markers would differentiate
      between severe and mild disease in RSV-infected children. METHODS: Blood and
      nasopharyngeal samples from 52 RSV-infected children were collected during acute
      infection and after recovery. Retrospectively, patients were categorized into
      three groups based on disease severity: mild (no supportive treatment), moderate
      (supplemental oxygen and/or nasogastric feeding), and severe (mechanical
      ventilation). Clinical data, number of flow-defined leukocyte subsets, and
      cytokine concentrations were compared. RESULTS: Children with severe RSV
      infection were characterized by young age; lymphocytopenia; increased interleukin
      (IL)-8, granulocyte colony-stimulating factor (G-CSF), and IL-6 concentrations;
      and decreased chemokine (C-C motif) ligand (CCL-5) concentrations in plasma. The
      combination of plasma levels of IL-8 and CCL-5, and CD4+ T-cell counts, with
      cutoff values of 67 pg/ml, 13 ng/ml, and 2.3 * 10(6)/ml, respectively,
      discriminated severe from mild RSV infection with 82% sensitivity and 96%
      specificity. CONCLUSION: This study demonstrates that the combination of CD4+ T
      cell counts and IL-8 and CCL-5 plasma concentrations correlates with disease
      severity in RSV-infected children. In addition to clinical features, these
      immunological markers may be used to assess severity of RSV infection and guide
      clinical management.

PMID- 23165451
TI  - Mathematics difficulties in extremely preterm children: evidence of a specific
      deficit in basic mathematics processing.
AB  - BACKGROUND: Extremely preterm (EP, <26 wk gestation) children have been observed
      to have poor academic achievement in comparison to their term-born peers,
      especially in mathematics. This study investigated potential underlying causes of
      this difficulty. METHODS: A total of 219 EP participants were compared with 153
      term-born control children at 11 y of age. All children were assessed by a
      psychologist on a battery of standardized cognitive tests and a number estimation
      test assessing children's numerical representations. RESULTS: EP children
      underperformed in all tests in comparison with the term controls (the majority of
      Ps < 0.001). Different underlying relationships between performance on the number
      estimation test and mathematical achievement were found in EP as compared with
      control children. That is, even after controlling for cognitive ability, a
      relationship between number representations and mathematical performance
      persisted for EP children only (EP: r = 0.346, n = 186, P < 0.001; control: r =
      0.095, n = 146, P = 0.256). CONCLUSION: Interventions for EP children may target
      improving children's numerical representations in order to subsequently remediate
      their mathematical skills.

PMID- 23165452
TI  - Tracking of clustered cardiovascular disease risk factors from childhood to
      adolescence.
AB  - BACKGROUND: Clustering of cardiovascular disease (CVD) risk factors has been
      found in children as young as 9 y of age. However, the stability of this
      clustering over the course of childhood has yet to be determined. The purpose of
      this study was to determine the tracking of clustered CVD risk from young school
      age through adolescence and to examine differences in tracking between levels of
      overweight/obesity and cardiorespiratory fitness (VO(2peak)). METHODS: Beginning
      at 6 y, children (n = 434) were measured three times in 7 y. Anthropometrics,
      blood pressure, and VO(2peak) were measured. Fasting blood samples were analyzed
      for CVD risk factors. A clustered risk score (z-score) was constructed by adding
      sex-specific z-scores for blood pressure, homeostatic model assessment (HOMA-IR),
      triglyceride (TG), skinfolds, and negative values of high-density lipoprotein
      cholesterol (HDLc) and VO(2peak). RESULTS: Significant tracking coefficients were
      found between clustered z-score at all time intervals (r = 0.514, 0.559, and
      0.381 between ages 6-9, 9-13, and 6-13 y, respectively, all P < 0.0001). Tracking
      was higher for low-fit children, whereas no clear pattern was found for different
      levels of body fat. CONCLUSION: We found that clustered z-score is a fairly
      stable characteristic through childhood. Implementation of preventive strategies
      could therefore start at early school age.

PMID- 23165453
TI  - Formation of an electron hole doped film in the alpha-Fe2O3 photoanode upon
      electrochemical oxidation.
AB  - Solar hydrogen generation by water splitting in photoelectrochemical cells (PEC)
      is an appealing technology for a future hydrogen economy. Hematite is a
      prospective photoanode material in this respect because of its visible light
      conjugated band gap, its corrosion stability, its environmentally benign nature
      and its low cost. Its bulk and surface electronic structure has been under
      scrutiny for many decades and is considered critical for improvement of
      efficiency. In the present study, hematite films of nominally 500 nm thickness
      were obtained by dip-coating on fluorine doped tin oxide (FTO) glass slides and
      then anodised in 1 molar KOH at 500, 600, and 700 mV for 1, 10, 120 and 1440
      minutes under dark conditions. X-ray photoelectron spectra recorded at the Fe 3p
      resonant absorption threshold show that the e(g) transition before the Fermi
      energy, which is well developed in the pristine hematite film, becomes depleted
      upon anodisation. The spectral weight of the e(g) peak decreases with the square
      root of the anodisation time, pointing to a diffusion controlled process. The
      speed of this process increases with the anodisation potential, pointing to
      Arrhenius behaviour. Concomitantly, the weakly developed t(2g) peak intensity
      becomes enhanced in the same manner. This suggests that the surface of the
      photoanode contains Fe(2+) species which become oxidized toward Fe(3+) during
      anodisation. The kinetic behaviour derived from the experimental data suggests
      that the anodisation forms an electron hole doped film on and below the hematite
      surface.

PMID- 23165454
TI  - [Hospital-acquired pneumonia].

PMID- 23165455
TI  - Tricyclic antidepressant use and risk of fractures: a meta-analysis of cohort and
      case-control studies.
AB  - Because studies of the association between tricyclic antidepressant (TCA)
      treatment and risk of fracture have shown inconsistent findings, we sought to
      assess whether people who take TCAs are at increased risk of fracture. Relevant
      studies published by June 2012 were identified through database searches of
      Scopus, MEDLINE, EMBASE, PsycINFO, ISI Web of Science, and WorldCat Dissertations
      and Theses from their inception, and manual searching of reference lists. Only
      original studies that examined the association between TCA treatment and risk of
      fracture were included. Two investigators independently conducted literature
      searches, study selection, study appraisal, and data abstraction using a
      standardized protocol. Disagreements were resolved by consensus. Twelve studies
      met inclusion criteria. Because of the heterogeneity of these studies, random
      effects models were used to pool estimates of effect. Overall, TCA use was
      associated with significantly increased fracture risk (relative risk [RR], 1.45;
      95% confidence interval [CI], 1.31-1.60; p < 0.001). Increased fracture risk
      associated with TCA use was also observed in studies that adjusted for bone
      mineral density (RR, 1.54; 95% CI, 1.24-1.90; p < 0.001) or depression (RR, 1.49;
      95% CI, 1.28-1.67; p < 0.001). Strength of association with TCA exposure duration
      >=6 weeks (RR, 1.13; 95% CI, 1.00-1.28) was substantially weaker than association
      with TCA exposure duration <6 weeks (RR, 2.40; 95% CI, 1.41-4.08). Prior TCA
      exposure had no significant effect on fracture risk (RR, 1.04; 95% CI, 0.86-1.26;
      p = 0.70). After accounting for publication bias, we found the overall
      association between TCA use and fracture risk to be slightly weaker (RR, 1.36;
      95% CI, 1.24-1.50) but still significant (p < 0.001). Findings of this meta
      analysis indicate that treatment with TCAs may convey an increased risk of
      fracture, independent of depression and bone mineral density.

PMID- 23165457
TI  - Steric and electronic effects on the configurational stability of residual chiral
      phosphorus-centered three-bladed propellers: tris-aryl phosphane oxides.
AB  - A series of tris-aryl phosphane oxides existing as residual enantiomers or
      diastereoisomers with substituents on the aryl rings differing in size and
      electronic properties were synthesized and characterized. Their electronic
      properties were evaluated on the basis of their electrochemical oxidation and
      reduction potentials together with those of the corresponding "blade bromides"
      (i.e., the naphthalene derivatives displaying the same substitution pattern of
      the tris-naphthyl phosphane oxide blades, with a bromo substituent where the
      phosphorus atom is located) determined by CV. The residual stereoisomeric
      phosphane oxides were isolated in a stereochemically pure state and were found to
      be highly configurationally stable at room temperature (stereoisomerization
      barriers of about 27 kcal mol(-1)). The chiroptical properties of the residual
      stereoisomers and the assignments of absolute configuration are discussed. The
      configurational stability of residual tris-aryl phosphane oxides was found to be
      scarcely influenced by the electronic properties of the substituents present on
      the aromatic rings constituting the blades, while steric effects play the most
      relevant role. Detailed theoretical calculations are in agreement with the
      experimental results and also contribute to a rational interpretation of the
      stereodynamics of these systems.

PMID- 23165459
TI  - Anisotropic lithiation behavior of crystalline silicon.
AB  - In this paper we demonstrate the anisotropic lithiation of silicon (Si).
      Therefore specimens with radiating Si beams were selectively covered with pure
      lithium (Li) and lithiation was investigated at different temperatures. Due to
      the radial arrangement, Si beams underwent a crystallographic orientation
      dependent lithiation. The experiments showed up to 40% faster lithiation in (110)
      crystallographic directions compared to (100) oriented Si, and a temperature
      dependence of the lithiation propagation with lithiation rates of up to 337 nm s(
      1) at 100  degrees C. These results were reflected in prior observation of (110)
      orientated Li-Si dendrites, formed after mechanical contact of Li with a Si
      device layer of a silicon-on-insulator wafer.

PMID- 23165461
TI  - Resistance studies of a dithiazol analogue, DBPR110, as a potential hepatitis C
      virus NS5A inhibitor in replicon systems.
AB  - Hepatitis C virus (HCV), a member of the Flaviviridae family, affects
      approximately 3% of the world's population and is becoming the leading cause of
      liver disease in the world. Therefore, the development of novel or more effective
      treatment strategies to treat chronic HCV infection is urgently needed. In our
      previous study, we identified a potential HCV NS5A inhibitor, BP008. After
      further systemic optimization, we discovered a more potent HCV inhibitor,
      DBPR110. DBPR110 reduced the reporter expression of the HCV1b replicon with a 50%
      effective concentration (EC(50)) and a selective index value of 3.9 +/- 0.9 pM
      and >12,800,000, respectively. DBPR110 reduced HCV2a replicon activity with an
      EC(50) and a selective index value of 228.8 +/- 98.4 pM and >173,130,
      respectively. Sequencing analyses of several individual clones derived from the
      DBPR110-resistant RNAs purified from cells harboring genotype 1b and 2a HCV
      replicons revealed that amino acid substitutions mainly within the N-terminal
      region (domain I) of NS5A were associated with decreased inhibitor
      susceptibility. P58L/T and Y93H/N in genotype 1b and T24A, P58L, and Y93H in the
      genotype 2a replicon were the key substitutions for resistance selection. In the
      1b replicon, V153M, M202L, and M265V play a compensatory role in replication and
      drug resistance. Moreover, DBPR110 displayed synergistic effects with alpha
      interferon (IFN-alpha), an NS3 protease inhibitor, and an NS5B polymerase
      inhibitor. In summary, our results present an effective small-molecule inhibitor,
      DBPR110, that potentially targets HCV NS5A. DBPR110 could be part of a more
      effective therapeutic strategy for HCV in the future.

PMID- 23165462
TI  - Systematic review and meta-analysis of vancomycin-induced nephrotoxicity
      associated with dosing schedules that maintain troughs between 15 and 20
      milligrams per liter.
AB  - In an effort to maximize outcomes, recent expert guidelines recommend more
      intensive vancomycin dosing schedules to maintain vancomycin troughs between 15
      and 20 mg/liter. The widespread use of these more-intensive regimens has been
      associated with an increase in vancomycin-induced nephrotoxicity reports. The
      purpose of this systematic literature review is to determine the nephrotoxicity
      potential of maintaining higher troughs in clinical practice. All studies
      pertaining to vancomycin-induced nephrotoxicity between 1996 and April 2012 were
      identified from PubMed, Embase, Cochrane Controlled Trial Registry, and Medline
      databases and analyzed according to Cochrane guidelines. Of the initial 240
      studies identified, 38 were reviewed, and 15 studies met the inclusion criteria.
      Overall, higher troughs (>= 15 mg/liter) were associated with increased odds of
      nephrotoxicity (odds ratio [OR], 2.67; 95% confidence interval [CI], 1.95 to
      3.65) relative to lower troughs of <15 mg/liter. The relationship between a
      trough of >= 15 mg/liter and nephrotoxicity persisted when the analysis was
      restricted to studies that examined only initial trough concentrations (OR, 3.12;
      95% CI, 1.81 to 5.37). The relationship between troughs of >= 15 mg/liter and
      nephrotoxicity persisted after adjustment for covariates known to independently
      increase the risk of a nephrotoxicity event. An incremental increase in
      nephrotoxicity was also observed with longer durations of vancomycin
      administration. Vancomycin-induced nephrotoxicity was reversible in the majority
      of cases, with short-term dialysis required only in 3% of nephrotoxic episodes.
      The collective literature indicates that an exposure-nephrotoxicity relationship
      for vancomycin exists. The probability of a nephrotoxic event increased as a
      function of the trough concentration and duration of therapy.

PMID- 23165463
TI  - Case report of exposure to voriconazole in the second and third trimesters of
      pregnancy.

PMID- 23165464
TI  - Role of the Mmr efflux pump in drug resistance in Mycobacterium tuberculosis.
AB  - Efflux pumps are membrane proteins capable of actively transporting a broad range
      of substrates from the cytoplasm to the exterior of the cell. Increased efflux
      activity in response to drug treatment may be the first step in the development
      of bacterial drug resistance. Previous studies showed that the efflux pump Mmr
      was significantly overexpressed in strains exposed to isoniazid. In the work to
      be described, we constructed mutants lacking or overexpressing Mmr in order to
      clarify the role of this efflux pump in the development of resistance to
      isoniazid and other drugs in M. tuberculosis. The mmr knockout mutant showed an
      increased susceptibility to ethidium bromide, tetraphenylphosphonium, and
      cetyltrimethylammonium bromide (CTAB). Overexpression of mmr caused a decreased
      susceptibility to ethidium bromide, acriflavine, and safranin O that was
      obliterated in the presence of the efflux inhibitors verapamil and carbonyl
      cyanide m-chlorophenylhydrazone. Isoniazid susceptibility was not affected by the
      absence or overexpression of mmr. The fluorometric method allowed the detection
      of a decreased efflux of ethidium bromide in the knockout mutant, whereas the
      overexpressed strain showed increased efflux of this dye. This increased efflux
      activity was inhibited in the presence of efflux inhibitors. Under our
      experimental conditions, we have found that efflux pump Mmr is mainly involved in
      the susceptibility to quaternary compounds such as ethidium bromide and
      disinfectants such as CTAB. The contribution of this efflux pump to isoniazid
      resistance in Mycobacterium tuberculosis still needs to be further elucidated.

PMID- 23165465
TI  - Limited activity of miltefosine in murine models of cryptococcal
      meningoencephalitis and disseminated cryptococcosis.
AB  - Miltefosine is an alkyl phosphocholine with good oral bioavailability and in
      vitro activity against Cryptococcus species that has gained interest as an
      additional agent for cryptococcal infections. Our objective was to further
      evaluate the in vivo efficacy of miltefosine in experimental in vivo models of
      cryptococcal meningoencephalitis and disseminated cryptococcosis. Mice were
      infected intracranially or intravenously with either C. neoformans USC1597 or
      H99. Miltefosine treatment (1.8 to 45 mg/kg of body weight orally once daily)
      began at either 1 h or 1 day postinoculation. Fluconazole (10 mg/kg orally twice
      daily) or amphotericin B deoxycholate (3 mg/kg intraperitoneally once daily)
      served as positive controls. In our standard models, miltefosine did not result
      in significant improvements in survival or reductions in fungal burden against
      either C. neoformans isolate. There was a trend toward improved survival with
      miltefosine at 7.2 mg/kg against disseminated cryptococcosis with the H99 strain
      but only at a low infecting inoculum. In contrast, both fluconazole and
      amphotericin B significantly improved survival in mice with cryptococcal
      meningoencephalitis and disseminated cryptococcosis due to USC1597. Amphotericin
      B also improved survival against both cryptococcal infections caused by H99.
      Combination therapy with miltefosine demonstrated neither synergy nor antagonism
      in both models. These results demonstrate limited efficacy of miltefosine and
      suggest caution with the potential use of this agent for the treatment of C.
      neoformans infections.

PMID- 23165466
TI  - In vitro activity of calcineurin and heat shock protein 90 Inhibitors against
      Aspergillus fumigatus azole- and echinocandin-resistant strains.
AB  - Due to the limited number of antifungals and the emergence of resistance, new
      therapies against invasive aspergillosis are needed. We show that calcineurin
      inhibitors are active in vitro against both azole- and echinocandin-resistant
      Aspergillus fumigatus strains. The heat shock protein 90 (Hsp90) inhibitor
      geldanamycin had modest activity when used alone, but its combination with
      caspofungin or tacrolimus (FK506) resulted in fungicidal activity against azole
      resistant strains. Targeting the Hsp90-calcineurin axis is a promising
      alternative strategy against azole-resistant A. fumigatus strains.

PMID- 23165468
TI  - Anthelmintic avermectins kill Mycobacterium tuberculosis, including multidrug
      resistant clinical strains.
AB  - Avermectins are a family of macrolides known for their anthelmintic activities
      and traditionally believed to be inactive against all bacteria. Here we report
      that members of the family, ivermectin, selamectin, and moxidectin, are
      bactericidal against mycobacterial species, including multidrug-resistant and
      extensively drug-resistant clinical strains of Mycobacterium tuberculosis.
      Avermectins are approved for clinical and veterinary uses and have documented
      pharmacokinetic and safety profiles. We suggest that avermectins could be
      repurposed for tuberculosis treatment.

PMID- 23165469
TI  - blaCTX-M-32 on an IncN plasmid in Escherichia coli from beef cattle in the United
      States.

PMID- 23165470
TI  - First report of blaNDM-1 in Raoultella ornithinolytica.

PMID- 23165471
TI  - Analysis of the posterior ramus of the lumbar spinal nerve: the structure of the
      posterior ramus of the spinal nerve.
AB  - BACKGROUND: Knowledge of neural anatomy is fundamental for safe, efficacious use
      of regional anesthesia. Spinal column procedures, such as a facet joint block,
      require an accurate understanding of neural pathways relative to anatomic
      structure. Since Bogduk's report it has been known that human lumbar posterior
      ramus of the spinal nerve (PRSN) comprises three, equally sized primary branches.
      However, inconsistencies and controversy remain over the exact locations and
      pathways of the peripheral portions of the PRSN branches. In this study, the
      authors investigated the detailed anatomy of the human PRSN. METHODS: The authors
      performed ventral dissection in seven cadavers to determine the layout of the
      PRSN between T10 and L4 spinal segments. They captured three-dimensional images
      with a laser scanner. For fine detail analysis, specimens from another cadaver
      were subjected to a modified Spalteholz technique to render all nonnerve tissue
      transparent. Computer graphics were used to create a three-dimensional structural
      model. RESULTS: All three PRSN branches emanated from an ipsilateral origin and
      passed posterior to the transverse process. The medial PRSN branch consistently
      passed between the mammillary and accessory processes under the mammilloaccessory
      ligament. The intermediate branch passed between the longissimus and iliocostalis
      muscles and extended to the skin. The lateral branch traveled far lateral from
      the origin. CONCLUSIONS: The authors created a 3D model of the PRSN in the lumbar
      segment, which may be useful for planning surgical approaches to dorsal areas of
      the vertebral column. In addition, this knowledge may improve the accuracy of
      procedures involving the spinal column, particularly radiofrequency neurolysis of
      the facet joint.

PMID- 23165472
TI  - Counting backward.

PMID- 23165473
TI  - Airway management in a child with a large retropharyngeal mass--a lesson learned:
      How conventional rules of endotracheal tube fixation can be deceptive.

PMID- 23165467
TI  - Intensification of antiretroviral therapy through addition of enfuvirtide in
      naive HIV-1-infected patients with severe immunosuppression does not improve
      immunological response: results of a randomized multicenter trial (ANRS 130
      Apollo).
AB  - We studied whether addition of enfuvirtide (ENF) to a background combination
      antiretroviral therapy (cART) would improve the CD4 cell count response at week
      24 in naive patients with advanced HIV disease. ANRS 130 Apollo is a randomized
      study, conducted in naive HIV-1-infected patients, either asymptomatic with CD4
      counts of <100/mm(3) or stage B/C disease with CD4 counts of <200/mm(3). Patients
      received tenofovir-emtricitabine with lopinavir-ritonavir (LPV/r) or efavirenz
      and were randomized to receive ENF for 24 weeks (ENF arm) or not (control arm).
      The primary endpoint was the proportion of patients with CD4 counts of >=
      200/mm(3) at week 24. A total of 195 patients were randomized: 73% had stage C
      disease, 78% were male, the mean age was 44 years, the median CD4 count was
      30/mm(3), and the median HIV-1 RNA load was 5.4 log(10) copies/ml. Eighty-one
      percent of patients received LPV/r. One patient was lost to follow-up, and eight
      discontinued the study (four in each arm). The proportions of patients with CD4
      counts of >= 200/mm(3) at week 24 were 34% and 38% in the ENF and control arms,
      respectively (P = 0.53). The proportions of patients with HIV-1 RNA loads of <50
      copies/ml were 74% and 58% at week 24 in the ENF and control arms, respectively
      (P < 0.02), and the proportion reached 79% in both arms at week 48. Twenty (20%)
      and 12 patients (13%) in the ENF and control arms, respectively, experienced at
      least one AIDS event during follow-up (P = 0.17). Although inducing a more rapid
      virological response, addition of ENF to a standard cART does not improve the
      immunological outcome in naive HIV-infected patients with severe
      immunosuppression.

PMID- 23165474
TI  - Transesophageal echocardiography: a novel technique for guidance and placement of
      an epidural catheter in infants.

PMID- 23165475
TI  - Glucose-neopentyl glycol (GNG) amphiphiles for membrane protein study.
AB  - The development of a new class of surfactants for membrane protein manipulation,
      "GNG amphiphiles", is reported. These amphiphiles display promising behavior for
      membrane proteins, as demonstrated recently by the high resolution structure of a
      sodium-pumping pyrophosphatase reported by Kellosalo et al. (Science, 2012, 337,
      473).

PMID- 23165477
TI  - Improving overall survival and overcoming adverse prognosis in the treatment of
      cytogenetically high-risk multiple myeloma.
AB  - Multiple myeloma (MM) is a heterogeneous disease with certain genetic features
      [e.g., t(4;14), del17p] associated with worse outcome. The introduction of
      thalidomide, lenalidomide, and bortezomib has dramatically improved the outlook
      for patients with MM, but their relative benefit (or harm) for different genetic
      patient subgroups remains unclear. Unfortunately, the small number of patients in
      each subgroup frequently limits the analysis of high-risk patients enrolled in
      clinical trials. Strategies that result in survival of high-risk genetic
      subgroups approximating that of patients lacking high-risk features are said to
      overcome the poor prognostic impact of these high-risk features. This outcome has
      been difficult to achieve, and studies in this regard have so far been limited by
      inadequate sample size. In contrast, strategies that compare the survival of high
      risk genetic subgroups randomized to different treatment arms can identify
      approaches that improve survival. This type of analysis is clinically useful,
      even if the absolute gains do not improve outcomes to levels seen in patients
      without high-risk cytogenetics. Reviewing available data in high-risk MM from
      this perspective, it appears that bortezomib has frequently been associated with
      improved survival, whereas thalidomide maintenance has sometimes been associated
      with a shorter survival.

PMID- 23165478
TI  - Targeted nanoparticle delivery overcomes off-target immunostimulatory effects of
      oligonucleotides and improves therapeutic efficacy in chronic lymphocytic
      leukemia.
AB  - Several RNA-targeted therapeutics, including antisense oligonucleotides (ONs),
      small interfering RNAs, and miRNAs, constitute immunostimulatory CpG motifs as an
      integral part of their design. The limited success with free antisense ONs in
      hematologic malignancies in recent clinical trials has been attributed to the CpG
      motif-mediated, TLR-induced prosurvival effects and inefficient target modulation
      in desired cells. In an attempt to diminish their off-target prosurvival and
      proinflammatory effects and specific delivery, as a proof of principle, in the
      present study, we developed an Ab-targeted liposomal delivery strategy using a
      clinically relevant CD20 Ab (rituximab)-conjugated lipopolyplex nanoparticle (RIT
      INP)- and Bcl-2-targeted antisense G3139 as archetypical antisense therapeutics.
      The adverse immunostimulatory responses were abrogated by selective B cell
      targeted delivery and early endosomal compartmentalization of G3139-encapsulated
      RIT-INPs, resulting in reduced NF-kappaB activation, robust Bcl-2 down
      regulation, and enhanced sensitivity to fludarabine-induced cytotoxicity.
      Furthermore, significant in vivo therapeutic efficacy was noted after RIT-INP
      G3139 administration in a disseminated xenograft leukemia model. The results of
      the present study demonstrate that CD20-targeted delivery overcomes the
      immunostimulatory properties of CpG-containing ON therapeutics and improves
      efficient gene silencing and in vivo therapeutic efficacy for B-cell
      malignancies. The broader implications of similar approaches in overcoming
      immunostimulatory properties of RNA-directed therapeutics in hematologic
      malignancies are also discussed.

PMID- 23165479
TI  - Haploidentical, unmanipulated, G-CSF-primed bone marrow transplantation for
      patients with high-risk hematologic malignancies.
AB  - Eighty patients with high-risk hematologic malignancies underwent unmanipulated,
      G-CSF-primed BM transplantation from an haploidentical family donor. Patients
      were transplanted in first or second complete remission (CR, standard-risk: n
      =45) or in > second CR or active disease (high-risk: n =35). The same regimen for
      GVHD prophylaxis was used in all cases. The cumulative incidence (CI) of
      neutrophil engraftment was 93% 0.1%. The 100-day CIs for II-IV and III-IV grade
      of acute GVHD were 24% 0.2% and 5% 0.6%, respectively. The 2-year CI of extensive
      chronic GVHD was 6% 0.1%. The 1-year CI of treatment-related mortality was 36%
      0.3%. After a median follow-up of 18 months, 36 of 80 (45%) patients are alive in
      CR. The 3-year probability of overall and disease-free survival for standard-risk
      and high-risk patients was 54% 8% and 33% 9% and 44% 8% and 30% 9%, respectively.
      In multivariate analysis, disease-free survival was significantly better for
      patients who had standard-risk disease and received transplantations after 2007.
      We conclude that unmanipulated, G-CSF-primed BM transplantation from
      haploidentical family donor provides very encouraging results in terms of
      engraftment rate, incidence of GVHD and survival and represents a feasible, valid
      alternative for patients with high-risk malignant hematologic diseases, lacking
      an HLA identical sibling and in need to be urgently transplanted. KEY POINTS:
      Haploidentical, unmanipulated, G-CSF-primed bone marrow transplantation.
      Haploidentical hematopoietic stem cell transplantation for hematologic
      malignancies.

PMID- 23165480
TI  - Discovery and validation of graft-versus-host disease biomarkers.
AB  - Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the most
      effective tumor immunotherapy available. Although allo-HSCT provides beneficial
      graft-versus-tumor effects, acute GVHD (aGVHD) is the primary source of morbidity
      and mortality after HSCT. Diagnosis of aGVHD is typically based on clinical
      symptoms in one or more of the main target organs (skin, liver, gastrointestinal
      tract) and confirmed by biopsy. However, currently available diagnostic and
      staging tools often fail to identify patients at higher risk of GVHD progression,
      unresponsiveness to therapy, or death. In addition, there are shortcomings in the
      prediction of GVHD before clinical signs develop, indicating the urgent need for
      noninvasive and reliable laboratory tests. Through the continuing evolution of
      proteomics technologies seen in recent years, plasma biomarkers have been
      identified and validated as promising diagnostic tools for GVHD and prognostic
      tools for nonrelapse mortality. These biomarkers may facilitate timely and
      selective therapeutic intervention but should be more widely validated and
      incorporated into a new grading system for risk stratification of patients and
      better-customized treatment. This review identifies biomarkers for detecting
      GVHD, summarizes current information on aGVHD biomarkers, proposes future
      prospects for the blinded evaluation of these biomarkers, and discusses the need
      for biomarkers of chronic GVHD.

PMID- 23165482
TI  - SPIB, a novel immunohistochemical marker for human blastic plasmacytoid dendritic
      cell neoplasms: characterization of its expression in major hematolymphoid
      neoplasms.
AB  - SPIB is an Ets transcription factor that is expressed exclusively in mature B
      cells, T-cell progenitors, and plasmacytoid dendritic cells. In the present
      study, we developed a novel mAb against the SPIB protein and characterized its
      expression in major hematolymphoid neoplasms, including a series of 45 cases of
      blastic plasmacytoid dendritic cell (BPDC) neoplasms and their potential
      cutaneous mimics. We found that SPIB is expressed heterogeneously among B- and T
      cell lymphoma types. Interestingly, SPIB is expressed in a large proportion of
      nongerminal center type DLBCLs. In cutaneous neoplasms, SPIB is overexpressed in
      all BPDC neoplasms, but none of its cutaneous mimics. SPIB remains overexpressed
      in all cases that lack 1 or 2 of the markers used for BPDC neoplasms (ie, CD4,
      CD56, TCL1, and CD123). We conclude that SPIB expression can be used as a tool
      for diagnosing BPDC neoplasms, but it needs to be tested in conjunction with the
      growing arsenal of markers for human plasmacytoid dendritic cells.

PMID- 23165483
TI  - Too much AKT turns PAX3-FKHR dead: a prospect of novel therapeutic strategy for
      alveolar rhabdomyosarcoma.

PMID- 23165481
TI  - Allogeneic, but not autologous, hematopoietic cell transplantation improves
      survival only among younger adults with acute lymphoblastic leukemia in first
      remission: an individual patient data meta-analysis.
AB  - Hematopoietic cell transplantation (HCT) and prolonged chemotherapy are standard
      postremission strategies for adult acute lymphoblastic leukemia in first complete
      remission, but the optimal strategy remains controversial. There are no
      randomized trials of allogeneic HCT. In the present study, updated individual
      patient data were collected and analyzed from studies with information on
      availability of matched sibling donor (used to mimic randomization) and from
      randomized trials of autograft versus chemotherapy. Data from 13 studies
      including 2962 patients, excluding Philadelphia chromosome-positive patients,
      showed a survival benefit for having a matched sibling donor for patients < 35
      years of age (OR = 0.79; 95% CI, 0.70-0.90, P = .0003) but not for those >= 35
      years of age (OR = 1.01; 95% CI, 0.85-1.19, P = .9; heterogeneity P = .03)
      because of the higher absolute risk of nonrelapse mortality for older patients.
      No differences were seen by risk group. There was a trend toward inferior
      survival for autograft versus chemotherapy (OR = 1.18; 95% CI, 0.99-1.41; P =
      .06). No beneficial effect of autografting was seen compared with chemotherapy in
      this analysis. We conclude that matched sibling donor myeloablative HCT improves
      survival only for younger patients, with an absolute benefit of approximately 10%
      at 5 years. Improved chemotherapy outcomes and reduced nonrelapse mortality
      associated with allogeneic HCT may change the relative effects of these
      treatments in the future.

PMID- 23165484
TI  - Evaluation of a fast-track programme for patients undergoing liver resection.
AB  - BACKGROUND: Recent developments in perioperative pathophysiology and care have
      documented evidence-based, multimodal rehabilitation (fast-track) to hasten
      recovery and to decrease morbidity and hospital stay for several major surgical
      procedures. The aim of this study was to investigate the effect of introducing
      fast-track principles for perioperative care in unselected patients undergoing
      open or laparoscopic liver resection. METHODS: This was a prospective study
      involving the first 100 consecutive patients who followed fast-track principles
      for liver resection. Catheters and drains were systematically removed early, and
      patients were mobilized and started eating and drinking from the day of surgery.
      An opioid-sparing multimodal pain treatment was given for the first week.
      Discharge criteria were: pain sufficiently controlled by oral analgesics alone,
      patient comfortable with discharge and no untreated complications. RESULTS:
      Median length of stay (LOS) for all patients was 5 days, with 2 days after
      laparoscopic versus 5 days following open resection (P < 0.001). Median LOS after
      minor open resections (fewer than 3 segments) was 5 days versus 6 days for major
      resections (3 or more segments) (P < 0.001). Simple right or left
      hemihepatectomies had a median LOS of 5 days. The readmission rate was 6.0 per
      cent and 30-day mortality was zero. CONCLUSION: Fast-track principles for
      perioperative care were introduced successfully and are safe after liver
      resection. Routine discharge 2 days after laparoscopic resection and 4-5 days
      after open liver resection may be feasible.

PMID- 23165485
TI  - Theoretical model of the effect of combined glenohumeral bone defects on anterior
      shoulder instability: a finite element approach.
AB  - The presence of either a Hill-Sachs or a bony Bankart defect has been indicated
      as a possible cause of subluxation and anterior shoulder dislocation. Previous
      studies investigated only the effects of isolated humeral or glenoid defects on
      glenohumeral instability. We investigated the effects on shoulder stability of
      both glenoid and humeral defects in the glenohumeral joint. A computer-based
      finite element approach was used to model the joint. A generic model was
      developed for cartilage and bone of the glenoid and humerus, using previously
      published data, and experiments were analyzed using static analysis with
      displacement control in the anterior-inferior direction. Simulations were run
      with a 50-N compressive load in the presence of both isolated and combined
      defects to analyze reaction forces and distance to dislocation. The distance to
      dislocation for normal joint was 13.6 mm at 90 degrees  abduction, which reduced
      to 9.7, 0, and 0 mm for largest isolated humerus defect, glenoid defect, and
      certain combined defects, respectively. For combined defects, stability ratio was
      decreased to 0% from 43%. Our results suggest that in the setting of combined
      bone defects, stability may be reduced more than what is known for isolated
      defects alone.

PMID- 23165486
TI  - Patterns of alcohol and tobacco use in Cambodia.
AB  - Few studies have considered whether the habitual use of tobacco in Southeast Asia
      is part of an established pattern of addiction that includes regular alcohol use.
      As part of a national survey of adult tobacco use in Cambodia (n = 13 988), we
      found that men who smoked were 2 times more likely to have drank alcohol in the
      past week (odds ratio = 2.53, 95% confidence interval = 2.10-3.03). By age 18 to
      25 years, 47% of male smokers drank alcohol, and this pattern of alcohol and
      tobacco use increased to >55% through the fifth decade. Women using smokeless
      tobacco with betel quid were more likely to be alcohol drinkers (odds ratio =
      1.49, 95% confidence interval = 1.12-1.98). Past week's drinking declined by late
      middle age and was associated with lower education and being currently married;
      the behavior was lower in some ethnic groups (ie, Cham). Our findings indicate an
      important association between alcohol and tobacco use, and raise the possibility
      that reducing alcohol consumption can be an important component of tobacco
      control. 

PMID- 23165487
TI  - Differentiating the associations of waist circumference and body mass index with
      cardiovascular disease risk in a Chinese population.
AB  - It is not known which obesity index best explains variations in cardiovascular
      disease risk across populations. The objective of this study was to differentiate
      the associations of waist circumference (WC) and body mass index (BMI) with
      cardiovascular disease risk in a Chinese population. Cardiovascular risk factors,
      WC, and BMI were measured in 13 817 adults aged more than 18 years in Shanghai.
      Higher WC tertiles were associated with higher blood pressure and higher
      cholesterol, triacylglycerol, and glucose concentrations within each tertile of
      BMI and vice versa. The odds ratios (ORs) of hypertension, dyslipidemia, and
      metabolic syndrome increased with successive WC (or BMI) tertiles after
      adjustment for BMI (or WC) and several covariates. However, BMI tertiles were not
      associated with the ORs of diabetes after adjustment for WC. WC may be better
      than BMI as an alternative measure of body fatness or fat distribution for
      predicting diabetic risks in Chinese adults. 

PMID- 23165488
TI  - Parental awareness and coverage of mass measles vaccination drive 2011: cross
      sectional survey in the metropolitan city of Karachi, Pakistan.
AB  - High measles incidence and frequent epidemics are reported in Pakistan, given the
      low coverage for measles vaccine. This study evaluated coverage of mass measles
      campaign 2011 and estimated parental awareness and determinants for low/no
      coverage. Household survey was conducted 4 months after the measles campaign in
      Karachi, Pakistan. Parents of children younger than 5 years were administered
      structured questionnaire about their knowledge and participation in measles
      campaign. Of 1020 eligible households, only 282 (28%) parents knew about measles
      supplementary immunization activity, mainly from public announcements (49%). Of
      these, 174 (62%) children received measles vaccine, whereas, 108 (38%) parents
      refused measles vaccine. Overall, only 17% children received measles vaccine
      during this campaign. Low maternal education, not having received DPT/Pentavalent
      3 vaccine, and routine vaccination from public Expanded Program on Immunization
      facility were significant determinants for low coverage. Measles vaccine coverage
      in Karachi remains low, and sporadic outbreaks of measles every 2 to 3 years are
      expected unless population coverage can be rapidly increased. 

PMID- 23165489
TI  - Musculoskeletal disorders among Thai women in construction-related work.
AB  - A cross-sectional study was conducted to determine the prevalence of
      musculoskeletal disorder symptoms and its risk factors among women rebar workers.
      A simple random sampling method was used and data were collected by face-to-face
      interview and ergonomic assessment from February to March 2011. A total of 272
      women rebar workers with at least 6 months' job experience participated in this
      study. The findings revealed that 57.7% of workers reported musculoskeletal
      disorder symptoms with low back and shoulders as the most common body parts
      affected (46.0%). Multiple logistic regression analysis indicated 2 variables
      that are significantly associated with musculoskeletal disorders: prolonged
      working hours (adjusted odds ratio = 7.63; 95% confidence interval = 2.06-28.31)
      and awkward posture (adjusted odds ratio = 43.79; 95% confidence interval = 17.09
      112.20). The high prevalence of musculoskeletal disorders among women rebar
      workers suggests that an appropriate ergonomic workstation design and ergonomic
      training for women rebar workers are necessary. 

PMID- 23165490
TI  - A stochastic model for early identification of infectious disease epidemics with
      application to measles cases in Bangladesh.
AB  - In this article, a stochastic modeling approach was employed for the detection of
      epidemics in advance that was based on a negative binomial model with 2
      components: an endemic component and an epidemic component. This study used
      monthly measles cases from January 2000 to August 2009 collected from the
      Expanded Program on Immunization, Bangladesh. General optimization routines
      provided the maximum likelihood estimates with corresponding standard errors. The
      negative binomial model with both seasonal endemic and epidemic components was
      shown to provide adequate fit with no measles epidemic during September 2008 to
      August 2009. 

PMID- 23165491
TI  - Toxic erythema of chemotherapy following i.v. BU plus fludarabine for allogeneic
      PBSC transplant.
AB  - I.v. BU plus fludarabine is an effective conditioning regimen for myeloid
      neoplasias with low treatment-related mortality. At standard doses, cutaneous
      toxicity has been reported in <5% of cases. As we observed a much higher
      incidence of cutaneous toxicity in patients who received predominantly
      pharmacokinetically based doses of BU, we performed a retrospective analysis of
      61 patients who received i.v. BU plus fludarabine (+/- antithymocyte globulin;
      ATG) as a conditioning regimen before allogeneic PBSC transplant. Of the 58
      evaluable patients, 33 (57%) developed cutaneous toxicity that fell within the
      spectrum of toxic erythema of chemotherapy (TEC). The median onset of TEC was 22
      days and most patients had multiple sites of involvement, with the groin, axillae
      and palms/soles being the favored sites. In men, scrotal involvement, sometimes
      severe, was also commonly observed. Initially, allergic reactions to antibiotics,
      fungal infections and GVHD were also considered until the clinical presentation
      of TEC became well recognized. In all patients, the skin healed without specific
      therapy but resolution often required several weeks. This series suggests that
      TEC is common after BU/fludarabine+/- ATG and it is important for transplant
      physicians to recognize, particularly as misdiagnosis could lead to inappropriate
      treatment.

PMID- 23165492
TI  - Allostimulatory activity of CD133+ hematopoietic cells.

PMID- 23165493
TI  - Front-line immunosuppressive treatment of acquired aplastic anemia.
AB  - In this article, front-line immunosuppressive therapy (IST) for acquired plastic
      anemia (AA) is illustrated and discussed. Also second-line and salvage options
      are briefly illustrated. First-line IST should consist of horse anti-thymocyte
      globulin (ATG) and CsA that has been shown to result in response rates between 60
      and 80%. CsA should be given for 12 months until transfusion independence is
      achieved and then tapered very slowly in the presence of a CR. Patients with a
      partial response are usually continued on CsA. Tight monitoring of the blood
      count during CsA tapering is necessary to identify early loss of response. G-CSF
      5 MUg/kg/day s.c. in the first 30 days has been shown to reduce infections and
      hospitalization and to identify early responders, as those who achieve
      neutrophils count of?0.5 * 10(9)/L by day +30. This schedule is recommended in
      the first month of therapy. Afterward, G-CSF can be considered in neutropenic
      febrile episodes. Patients not achieving transfusion independence after a first
      course of IST may be considered for second-line IST, or for an allogeneic
      hematopoietic SCT depending on patient age, ongoing infection, neutrophil count
      and transfusion requirements. Third-line IST is rarely given, but some options
      are discussed.

PMID- 23165494
TI  - Standard treatment of acquired SAA in adult patients 18-40 years old with an HLA
      identical sibling donor.
AB  - Matched related donor allo-SCT is the treatment of choice for patients with
      severe aplastic anemia (SAA) younger than 40 years of age. The standard
      conditioning regimen for such patients is cyclophosphamide with antithymocyte
      globulin. Unmanipulated BM is the best stem cell source for aplastic anemia
      patients going for SCT. Post-transplant GVHD prophylaxis with cyclosporine should
      be continued for 1 year. Early graft failure is rare but potentially life
      threatening complication of SCT that can be managed with salvage SCT using more
      intense conditioning regimen.

PMID- 23165495
TI  - Diagnosis of acquired aplastic anemia.
AB  - Since the introduction of the concept of aplastic anemia (AA) by Paul Ehrlich in
      1888 and despite the current better understanding of the underlying mechanisms
      involved in this disease, a clear delimitation among BM failure syndromes is
      still a matter of debate. The diagnosis of AA can be difficult basically due to
      the overlapping morphological characteristics with other BM failure disorders.
      This paper reviews critical data relevant to the diagnosis of acquired AA and
      recommends work out steps and main considerations to determine severity and
      characterization of the disease. The diagnostic challenge in the differentiation
      between AA and hypoplastic myelodysplastic syndromes is also addressed. The
      definition of the response criteria to treatment belongs to the diagnostic tasks
      and it is included in this review as well as an overview of novel tools for the
      diagnosis of AA.

PMID- 23165496
TI  - Treatment and hematopoietic SCT in aplastic anemia.

PMID- 23165497
TI  - Treatment of adult ALL with central nervous system involvement at diagnosis using
      autologous and allogeneic transplantation: a study from the Societe Francaise de
      Greffe de Moelle et de Therapie Cellulaire.
AB  - To assess the role of hematopoietic SCT (HSCT) in adult ALL patients with central
      nervous system involvement at diagnosis, we retrospectively analyzed 90 patients
      who underwent autologous HSCT (auto-HSCT group; n=27) or allogeneic HSCT (allo
      HSCT group; n=63) and reported to the Societe Francaise de Greffe de Moelle et de
      Therapie Cellulaire registry between 1994 and 2008. At the time of
      transplantation, 67 patients (74%) were in first CR, 15 (17%) in CR?2 and 8 (9%)
      with progressive disease. The 5-year probabilities of overall survival (OS) and
      disease-free survival (DFS) were 52% and 46% for the allo-HSCT and 37% and 33%
      for the auto-HSCT groups, respectively (P=NS). The TRM at 5 years was 29.8% for
      the allo-HSCT group and 3.7% for the auto-HSCT group. Using univariate analysis,
      a time for transplantation of <12 months, the remission status at
      transplantation, the use of high-dose TBI and the number of the transplant were
      all determined to be prognostic factors for improved DFS and OS probabilities.
      Using multivariate analysis, we demonstrated that both the use of high-dose TBI
      and the remission status had a favorable impact on OS. Although the DFS and OS
      were better in the allo-HSCT group, the differences were not statistically
      significant.

PMID- 23165498
TI  - Pediatric allo-SCT for malignant and non-malignant diseases: impact on health
      related quality of life outcomes.
AB  - The objective of this study was prospectively to investigate the health-related
      quality of life (HRQOL) of 80 pediatric recipients of allo-SCT for malignant and
      non-malignant diseases. The PedsQL 4.0 was used to assess self-reported physical,
      emotional and social functioning of children ?5 years old once, pre-allo-SCT and
      on days +100, +180, +365 and +730. Emotional and social functioning was stable
      pre-to-post-allo-SCT and comparable to the normative sample (P>0.05), and
      physical functioning was 17 points lower pre-allo-SCT (P?0.01) with improved
      scores equivalent to the norms by day +730. Lower physical scores were reflected
      by 50-54% of children reporting difficulties with movement, strength, pain and
      fatigue. At baseline, children ages 5-7 reported lower social functioning
      (P<0.05) and patients with non-malignant disease reported better physical
      functioning (P<0.05). Emotional functioning in ages 8-12 improved over time
      (P<0.05). More than 50% of the participants were minority and their HRQOL was
      similar to non-minority participants. Physical functioning significantly improved
      for recipients of reduced-toxicity conditioning (P?0.01), significantly worsened
      for patients with chronic GVHD (cGVHD; P<0.05), and significantly decreased in
      recipients of matched-unrelated donor transplant who developed cGVHD (P<0.05).
      Multidisciplinary efforts are necessary to identify and support pediatric
      patients' physical needs to improve functional outcomes.

PMID- 23165499
TI  - Frequency of CD4(+)FOXP3(+) regulatory T-cells at early stages after HLA
      mismatched allogeneic hematopoietic SCT predicts the incidence of acute GVHD.
AB  - Acute GVHD (aGVHD) is a major obstacle to allogeneic hematopoietic SCT
      (alloHSCT). Although it is thought that aGVHD is initiated in secondary lymphoid
      organs at a very early stage of alloHSCT, whether CD4(+)FOXP3(+) regulatory T
      cells (Tregs) have an impact on aGVHD development during this period remains
      unclear. Here, we measured Tregs in peripheral blood as early as possible after
      HLA-mismatched alloHSCT, and assessed the incidence of aGVHD. Flow cytometric
      analyses revealed that at the second week after HSCT, patients with aGVHD had
      significantly (P=0.018) lower Treg:CD4(+)T-cell ratios than those without aGVHD.
      As these differences were seen before the development of aGVHD, these ratios can
      predict the incidence of aGVHD. The cumulative incidence of aGVHD in patients
      with ratios of <9% was significantly higher than that in patients with ratios of
      ?9% (P=0.0082, log-rank test). Additionally, the specific ratio of Tregs:CD4(+)T
      cells was the most significant value among all other possible lymphocyte
      associated ratios and absolute cell counts. These findings suggest that the ratio
      of Tregs:CD4(+)T-cells at the second week post HLA-mismatched alloHSCT might be a
      potent predictor of aGVHD in these patients. The practical efficacy of this
      finding should be verified in further interventional studies.

PMID- 23165500
TI  - Chest health surveillance utility in the early detection of bronchiolitis
      obliterans syndrome in children after allo-SCT.
AB  - To prospectively assess whether periodic chest health surveillance is beneficial
      for the early detection of bronchiolitis obliterans syndrome (BOS) in children
      after allo-SCT. Children up to 18 years of age receiving allo-SCT from September
      2009 to September 2011 were included. Surveillance consisted of the following: a
      7-item respiratory system questionnaire of cough, wheeze and shortness of breath;
      focused physical examination; and pulmonary function test (PFT) conducted before
      SCT and at 1, 3, 6, 9, 12, 18 and 24 months after SCT. Thirty-nine patients were
      enrolled. Five children developed BOS at a median time of 192 days (range 94
      282). Positive response comparisons between the BOS group vs the non-BOS group
      were NS for history questionnaire (P=0.2), heart rate (P=0.3), respiratory rate
      (P=0.3) and oxygen saturation monitoring (P=0.8). Differences between the two
      groups for chest auscultation and PFT were statistically significant (P=0.03 and
      P=0.01, respectively). However, chest auscultation in the BOS group was only
      positive after BOS diagnosis. PFT reduction was evident in the asymptomatic phase
      (BOS group 33%; non-BOS group 4.5%, P=0.01). Changes in PFT, but not
      history/physical examination, allow the early detection of BOS in children after
      SCT. Our study is limited by the small sample size.

PMID- 23165501
TI  - Effectiveness of etoposide chemomobilization in lymphoma patients undergoing auto
      SCT.
AB  - The effectiveness of stem cell mobilization with G-CSF in lymphoma patients is
      suboptimal. We reviewed our institutional experience using chemomobilization with
      etoposide (VP-16; 375 mg/m(2) on days +1 and +2) and G-CSF (5 MUg/kg twice daily
      from day +3 through the final day of collection) in 159 patients with lymphoma.
      This approach resulted in successful mobilization (>2 * 10(6) CD34+ cells
      collected) in 94% of patients (83% within 4 apheresis sessions). Fifty-seven
      percent of patients yielded at least 5 * 10(6) cells in ?2 days and were defined
      as good mobilizers. The regimen was safe with a low rate of rehospitalization.
      Average costs were $14 923 for good mobilizers and $27 044 for poor mobilizers
      (P<0.05). Using our data, we performed a 'break-even' analysis that demonstrated
      that adding two doses of Plerixafor to predicted poor mobilizers at the time of
      first CD34+ cell count would achieve cost neutrality if the frequency of good
      mobilizers were to increase by 21%, while the frequency of good mobilizers would
      need to increase by 25% if three doses of Plerixafor were used. We conclude that
      chemomobilization with etoposide and G-CSF in patients with lymphoma is
      effective, with future opportunities for cost-neutral improvement using novel
      agents.

PMID- 23165503
TI  - Persistent human rhinovirus type C infection of the lower respiratory tract in a
      pediatric cord blood transplant recipient.

PMID- 23165502
TI  - IL15 levels on day 7 after hematopoietic cell transplantation predict chronic
      GVHD.
AB  - Chronic GVHD (cGVHD) is an important complication of allogeneic hematopoietic
      cell transplantation (HCT). As preemptive therapy might be efficacious if
      administered early post transplant, we set out to determine whether cGVHD can be
      predicted from the serum level of a biomarker on day 7 or 28. In a discovery
      cohort of 153 HCT recipients conditioned with BU, fludarabine and rabbit
      antithymocyte globulin (ATG), we determined serum levels of B-cell-activating
      factor, vascular endothelial growth factor, soluble TNF-alpha receptor 1, soluble
      IL2 receptor alpha, IL5, IL6, IL7, IL15, gamma-glutamyl transpeptidase,
      cholinesterase, total protein, urea and ATG. Patients with low levels of IL15
      (<30.6 ng/L) on day 7 had 2.7-fold higher likelihood of developing significant
      cGVHD (needing systemic immunosuppressive therapy) than patients with higher IL15
      levels (P<0.001). This was validated in a validation cohort of 105 similarly
      treated patients; those with low IL15 levels had 3.7-fold higher likelihood of
      developing significant cGVHD (P=0.001). Low IL15 was not associated with relapse;
      it trended to be associated with acute GVHD and was associated with low infection
      rates. In conclusion, low IL15 levels on day 7 are predictive of cGVHD, and thus
      could be useful in guiding preemptive therapy.

PMID- 23165504
TI  - The first examples of thiogermanate anion [GeS3(SH)](3-) as a bridging ligand to
      a lanthanide complex.
AB  - Two new lanthanoid thiogermanates [Ln(dien)(2)(MU-eta(1),eta(2)-GeS(3)(SH))](n)
      {Ln = La(), Nd(); dien = diethylenetriamine} were solvothermally synthesized and
      structurally characterized. Both and represent the first examples of the soft
      Lewis basic [GeS(3)(SH)](3-) anions as tridentate bridging ligand to hard Lewis
      acidic Ln(3+) ions. Both and exhibit semiconducting properties with absorption
      band edges of 2.11 eV for and 2.28 eV for . The DFT study of indicates a direct
      band gap with an electronic transfer excitation of S 3p to both Ge 4s and La 5d
      orbital electrons.

PMID- 23165505
TI  - Clinical trials in spinal cord injury: lessons learned on the path to
      translation. The 2011 International Spinal Cord Society Sir Ludwig Guttmann
      Lecture.
AB  - After three decades of clinical research on interventions to improve neurological
      outcomes in persons with spinal cord injury (SCI), the promise of preclinical
      discovery has yet to be translated into a consensus standard of care treatment.
      Nonetheless, SCI researchers remain hopeful that advances in preclinical
      discovery coupled with improved clinical trial performance will yield effective
      restorative treatment. This historical review of key studies in SCI over the past
      30 years illustrates the progress that has been achieved in establishing a high
      standard in the conduct of clinical research while providing important lessons
      for improving trial design, conduct and reporting. Through application of these
      lessons, the performance of SCI trials can be improved, thereby shortening the
      pathway to successful translation and the development of effective therapies.

PMID- 23165506
TI  - The emulsified perfluorocarbon Oxycyte improves spinal cord injury in a swine
      model of decompression sickness.
AB  - STUDY DESIGN: A prospective, animal model for pharmacological intervention of
      decompression sickness (DCS), including spinal cord (SC) injury. BACKGROUND:
      Signs and symptoms of DCS can include joint pain, skin discoloration,
      cardiopulmonary congestion and SC injury; severity ranges from trivial to fatal.
      Non-recompressive therapy for DCS may improve time-to-treatment and therefore
      impact mortality and morbidity. OBJECTIVES: Oxycyte at 5 cc kg(-1) provides both
      SC protection and statistically significant survival benefit in a swine model of
      DCS. The purpose of this study was to test whether a reduced dose of Oxycyte (3
      cc kg(-1)) would provide similar benefit. SETTING: Silver Spring, MD, USA
      METHODS: Male Yorkshire swine (N=50) underwent a non-linear compression profile
      to 200 fsw (feet of sea water), which was identical to previous work using the 5
      cc kg(-1) dose of Oxycyte. After 31 min of bottom time, decompression was
      initiated at 30 fsw per minute until surface pressure was reached. Following
      decompression and the onset of DCS, intravenous Oxycyte or saline was
      administered with concurrent 100% O(2) for 1 h. The primary end point was DCS
      induced mortality, with Tarlov score and SC histopathology as secondary end
      points. RESULTS: Oxycyte administration of 3 cc kg(-1) following surfacing
      produced no significant detectable survival benefit. Animals that received
      Oxycyte, however, had reduced SC lesion area. CONCLUSION: Further studies to
      determine the lowest fully efficacious dose of Oxycyte for the adjunct treatment
      of DCS are warranted.

PMID- 23165507
TI  - Falls in patients with HTLV-I-associated myelopathy/tropical spastic paraparesis
      (HAM/TSP).
AB  - STUDY DESIGN: Cross-sectional study. OBJECTIVES: To determine the prevalence of
      falls in human T-cell lymphotropic virus type I (HTLV-I)-associated
      myelopathy/tropical spastic paraparesis (HAM/TSP) patients and possible factors
      associated to their occurrence. SETTING: Instituto de Pesquisa Clinica Evandro
      Chagas, Fundacao Oswaldo Cruz (FIOCRUZ) - Brazil. METHODS: Thirty-six HAM/TSP
      patients able to walk at least 20 m were assessed by a questionnaire. Data
      regarding gender, age, duration of disease (DD), HTLV-I proviral load (HPL),
      frequency of physical activity (FCA), use of walking aids, functional ambulation
      level, the number of falls and associated injuries in the last year were
      reviewed. Multiple correspondence analysis was used to group characteristics of
      this sample according to the fall occurrence. RESULTS: The prevalence of falls
      was 63.9% and we observed injuries in 47.8% of the cases. Four groups were
      identified in the descriptive analysis. One group was formed by faller
      individuals, men <60 years, independent ambulation, FCA>=3 times per week and HPL
      <6.6 copies per 100 cells (group B). The other one comprised non-faller patients,
      women >=60 years, restricted ambulation, DD >=7 years, use of orthosis, FCA 0-1
      time per week and HPL >=6.6 copies per 100 cells (group D). The others two groups
      comprised individuals that did not use orthosis (group A) and those that FCA was
      two times per week and DD <7 years (group C). CONCLUSION: Falls occur in roughly
      two-thirds of ambulatory HAM/TSP patients and are associated with significant
      morbidity. Further studies with a larger number of patients are necessarily to
      identify risk factors in order to elaborate specific programs to prevent falls in
      this population.

PMID- 23165508
TI  - Secondary mutations in BRCA2 associated with clinical resistance to a PARP
      inhibitor.
AB  - PARP inhibitors (PARPi) for the treatment of BRCA1 or BRCA2 deficient tumours are
      currently the focus of seminal clinical trials exploiting the concept of
      synthetic lethality. Although clinical resistance to PARPi has been described,
      the mechanism underlying this has not been elucidated. Here, we investigate
      tumour material from patients who had developed resistance to the PARPi olaparib,
      subsequent to showing an initial clinical response. Massively parallel DNA
      sequencing of treatment-naive and post-olaparib treatment biopsies identified
      tumour-specific BRCA2 secondary mutations in olaparib-resistant metastases. These
      secondary mutations restored full-length BRCA2 protein, and most likely cause
      olaparib resistance by re-establishing BRCA2 function in the tumour cells.

PMID- 23165509
TI  - Laparoscopic repyloromyotomy following open pyloromyotomy for recurrent pyloric
      stenosis: a case report and review of the literature.

PMID- 23165510
TI  - Fetal surgery in Zurich: key features of our first open in utero repair of
      myelomeningocele.

PMID- 23165511
TI  - Late presentation of congenital diaphragmatic hernia: report of three cases.

PMID- 23165512
TI  - Biliary atresia and inguinal hernia.

PMID- 23165513
TI  - Congenital spigelian hernia and undescended testis: pitfalls in the
      transformation of a "coexistence" to "sequence" and "new syndrome".

PMID- 23165514
TI  - Epispadias repair after failed surgery in childhood.
AB  - INTRODUCTION: Redo surgery in failed epispadias presents a great challenge. Our
      aim was to present a radical approach for correction of penile deformities as
      well as urethral reconstruction in patients after failed epispadias repair.
      MATERIALS AND METHODS: Between January 2006 and January 2011, 13 patients, aged
      13 to 22 years, underwent redo surgery due to failed epispadias repair in
      childhood. All patients presented with severe dorsal curvature and short urethra.
      First stage included penile disassembly technique with complete separation of
      corporal bodies, urethral dissection, and transposition and subtotal glans
      mobilization. Residual dorsal curvature was corrected by tunical incision and
      grafting of the defect. Short urethra was dissected and transposed ventrally with
      opening at the base of the penis. Penile entities were reassembled in normal
      anatomical relationship. Penile body was covered using available vascularized
      skin flaps. After 6 months, second stage was performed and included
      reconstruction of the penile urethra using buccal mucosa graft and scrotal
      hairless skin flap. RESULTS: Follow-up ranged from 12 to 60 months (mean 33
      months). Acceptable outcome is achieved in all the patients. Complete penile
      lengthening and straightening is obtained in 10 out of 13 patients. Mild
      curvature is noted in three patients without consequences. Satisfactory sexual
      activity was reported from nine patients. One patient developed fistula that was
      closed after 4 months, whereas all other patients reported normal voiding with no
      difficulties. CONCLUSIONS: Redo surgery of failed epispadias is very demanding
      procedure. Radical approach in these cases is necessary for complete repair of
      all penile deformities with satisfactory postoperative outcome.

PMID- 23165515
TI  - Day-case laparoscopic cholecystectomy in childhood: outcomes from a clinical care
      pathway.
AB  - AIM: The aim of this study was to report clinical outcomes following the use of a
      pediatric day-case laparoscopic cholecystectomy (DCLC) clinical care pathway. The
      pathway was modified in September 2009 and we compare the clinical outcomes
      before and after this modification. METHODS: A care pathway for DCLC was
      introduced in 2008 with emphasis on the day of admission, timing of surgery,
      choice of anesthetic agents, analgesia, postoperative feeding, mobilization, and
      pain scoring. Demographic and clinical data were recorded prospectively from
      January 2008 to January 2012. In September 2009, two modifications were made to
      the pathway. Induction of anesthesia was changed to total intravenous anesthesia,
      using propofol (target 4 to 6 ug/mL) and remifentanil (target 3 to 5 ng/mL) and
      the use of the gaseous anesthetic sevoflurane was eliminated with the aim of
      reducing the risk of postoperative nausea and vomiting (PONV). The postoperative
      feeding regime was changed from unrestricted to light diet for 72 hours. The rest
      of the pathway was unchanged. Data before (group 1) and following the
      modifications (group 2) were compared. RESULTS: We admitted 25 children with
      symptomatic cholelithiasis for DCLC under the care of one surgeon: 12 in group 1
      and 13 in group 2. There were no significant differences in age between group 1
      (median 13 [range 6 to 15] years) and group 2 (median 15 [9 to 16] years) (p =
      0.07). There were no intra- or postoperative complications. The day-case rate
      increased from 6/12 (50%) in group 1 to 12/13 (92%) in group 2 (p = 0.03). The
      incidence of PONV reduced from 7/12 (58%) in group 1 to 0/13 in group 2 (p =
      0.002). PONV in group 1 resulted in overnight stay (n = 6) and readmission (n =
      1). One patient in group 2 had an overnight stay due to poor mobilization.
      CONCLUSIONS: Adoption of a DCLC pathway is feasible and safe for children.
      Emphasis on adequate pain management and avoidance of PONV results in a high rate
      of day-case surgery equivalent to that achieved in adult practice.

PMID- 23165516
TI  - Donor hypernatremia influences outcomes following pediatric liver
      transplantation.
AB  - INTRODUCTION: With the rising demand for liver transplantations (LTs), and the
      shortage of organs, extended criteria including donor hypernatremia have been
      adopted to increase the donor pool. Currently, there is conflicting evidence on
      the effect of donor hypernatremia on outcomes following LT. Our aim was to
      investigate differences in outcome in patients receiving grafts from
      hypernatremic donors compared with patients receiving grafts from normonatremic
      donors in the pediatric population. METHODS: We retrospectively reviewed 94
      pediatric patients with LTs from 1994 to 2011. We divided the patients into two
      groups: patients receiving organs from donors with sodium levels < 150 umol/L, n
      = 67 (group 1), and patients receiving organs from donors with sodium levels >=
      150 umol/L, n = 27 (group 2). Using proportions and means, we analyzed patient
      age, sex, weight, model for end-stage liver disease (MELD) score, primary
      diagnosis, emergency of procedure, intraoperative transfusion volume, cold
      ischemia time, donor age, graft type, and postoperative graft function. Rates of
      mortality, rejection, early biliary, infectious, and vascular complications were
      calculated. RESULTS: Mean age was 3.9 years in group 1 and 3.7 years in group 2
      (p = 0.69). Mean weight and MELD scores were similar in the two study groups
      (16.0 vs. 15.9 and 21.2 vs. 22.0, respectively). There were no significant
      differences in mean cold ischemia times 6.4 versus 6.9 hours (p = 0.29), and mean
      intraoperative transfusion volumes 1,068.5 mL versus 1,068.8 mL (p = 0.89). There
      were no statistically significant differences in mortality rates (7.3 vs. 11.1%,
      p = 0.68). Prothrombin time (PT) at day 10 post-LT was significantly lower in
      group 2 (79 vs. 64, p = 0.017), and there was a higher relative risk (RR) for
      early thrombotic vascular complications in group 2 (RR = 2.48); however, this was
      not significant (p = 0.26). No significant differences in RR for rejection (0.97,
      p = 0.86), viral infections (1.24, p = 0.31), bacterial infections (0.86, p =
      0.62), or early biliary complications (1.03, p = 1.00) were observed. CONCLUSION:
      In pediatric LT patients receiving grafts from hypernatremic donors, there are no
      significant increases in rates of mortality, rejection, early biliary, and
      infectious complications. However, there is a statistically significant lower PT
      at postoperative day 10 following transplantation, and a more than double RR for
      early thrombotic vascular complications although this was not statistically
      significant.

PMID- 23165518
TI  - Laparoscopic extravesical ureteral reimplantation (LEVUR): a multicenter
      experience with 95 cases.
AB  - INTRODUCTION: Minimally invasive techniques have been used to treat
      vesicoureteral reflux (VUR) on pediatric patients. The aim of this study is to
      review the experience of the laparoscopic approach for VUR by the laparoscopic
      extravesical ureteral reimplantation (LEVUR) Lich-Gregoir technique. MATERIALS
      AND METHODS: We performed a multicentric retrospective study. From 2001 to 2009,
      81 pediatric patients with VUR constituting 95 ureteral units underwent LEVUR.
      Reflux was grade II in 32%, grade III in 55%, and grade IV in 8%. RESULTS: LEVUR
      was performed successfully on the 81 patients with 95 ureteral units. Mean
      operative time was 105 minutes for left-sided reimplants, 70 minutes for right
      sided, and 180 minutes for bilateral reimplants. Mean hospital stay was 1.6 days.
      Urinary catheter was kept in place for a mean time of 0.5 days. Follow-up was
      achieved for at least 1 year with regular clinic visits, urinalysis, ultrasound,
      and voiding cystourethrogram. Four patients (4.2%) had evidence of recurrent VUR
      in a follow-up of 6 to 36 months after antireflux surgery. CONCLUSIONS: Although
      new endoscopic techniques have been widely available for VUR, they have a lower
      success rate and might require multiple attempts before success. We report that
      LEVUR has an acceptable success rate (95.8%) and durability compared with open
      and endoscopic procedures.

PMID- 23165517
TI  - Early enteral stressors in newborns increase inflammatory cytokine expression in
      a neonatal necrotizing enterocolitis rat model.
AB  - INTRODUCTION: Inflammation in the premature intestine is a key factor that leads
      to the development of necrotizing enterocolitis (NEC). Activation of nuclear
      factor kappa B (NF-kappaB) and subsequent inflammation increases the severity of
      NEC. The aim of this study was to investigate the early temporal expression of
      inflammatory markers and activation of NF-kappaB in a neonatal rat model of NEC.
      METHODS: Pre- and full-term newborn Sprague-Dawley rat pups were sacrificed at
      birth, 1.5, 4, 8, and 24 hours after receiving their first feed. Control pups
      were vaginally delivered and mother fed; NEC was induced by a combination of
      gavage feeding formula, hypoxia, and enteral lipopolysaccharide (LPS); and
      formula fed pups were fed every 4 hours with infant formula. Ileal tissue was
      collected for immunohistochemistry, real-time polymerase chain reaction (RT-PCR)
      and enzyme-linked immunosorbent assay. Serum was collected for cytokine content.
      Fold change of expression of inducible nitric oxide synthase (iNOS), interleukin
      (IL)-1beta, IL-6, tumor necrosis factor-alpha (TNF-alpha), IL-10, NF-kappaB p65,
      and IkappaBalpha used RT-PCR. Data were analyzed by paired two-tailed t test,
      expressed as mean +/- standard error of the mean, and p <= 0.05 considered
      significant. RESULTS: No histologic injury was evident in ileal sections. At 1.5
      h, iNOS expression increased twofold over control in NEC pups (2.1 vs. 1.0, p <=
      0.05) and remained elevated at 24 h (0.7 vs. 9.4, p <= 0.05). IL-1beta and IL-6
      reached a peak at 24 h in NEC tissue compared with control. IL-10 expression rose
      in NEC pups after 4 h of insult and remained elevated in formula and NEC stressed
      pups. Coincident with an increase in p65 translocation into the nucleus and a
      reduction of IkappaBalpha detected in the cytoplasm, increased transcription of
      IkappaBalpha occurs. CONCLUSION: These findings suggest that NF-kappaB activation
      initiates inflammation early in the course of NEC resulting in increased
      proinflammatory protein expression, underscoring the importance of the
      inflammatory response in this NEC model, which precedes evidence of histological
      injury.

PMID- 23165519
TI  - "The umbilical fat sign": an important and consistent landmark during single
      port/incision laparoscopic surgery and standard laparoscopy.
AB  - INTRODUCTION: During single port laparoscopic surgery (SPLS), access is obtained
      through the umbilicus and the scar is hidden within the scar of the umbilicus for
      providing good cosmesis. It is essential that the incision be well planned so as
      to get the maximum exposure through the umbilical incision. The umbilical fat
      sign is an important landmark to achieve this. PURPOSE: The aim of this study is
      to retrospectively review importance of the umbilical fat sign as a landmark for
      peritoneal access during SPLS in children. METHOD: A retrospective chart review
      of 57 children (33 males and 24 females) who underwent single port access surgery
      at Texas Children's Hospital from April 2009 to December 2010 was conducted. The
      median age of the patients was 10.8 years, ranging from 4 to 17 years. TECHNIQUE:
      The limits of the umbilicus were marked using a marking pen. A vertical incision
      is made through the center of the umbilical scar. It is of vital importance to
      maintain the incision in the exact center of the scar tissue. Skiving away from
      the center makes the entry in the peritoneal cavity harder and prolongs
      peritoneal access time. During all the single port cases, we have done so far we
      have noted that if we are in the center of the scar then we always see a blob of
      fat ("umbilical fat" sign) in the center. If we use a probe or grooved director
      through this fat direct access is obtained in the peritoneal cavity. Incision can
      then be extended on both sides and be kept to the limits of the umbilical ring.
      Peritoneal access can be obtained in 1 to 2 minutes using this approach.
      Umbilical reconstruction is the best performed with this approach. RESULTS: One
      child developed signs of wound infection and was treated successfully with
      antibiotics for 5 days. Scars healed well in all cases with no wound dehiscence.
      No umbilical scars were visible at follow-up (3 to 4 weeks postoperatively).
      CONCLUSION: Umbilical fat sign is an important landmark for surgeons during SPLS
      for direct and quick peritoneal access and better reconstruction of the
      umbilicus.

PMID- 23165520
TI  - Serial intravesical pressure measurements can predict the presence and the
      severity of necrotizing enterocolitis.
AB  - BACKGROUND AND AIMS: Necrotizing enterocolitis (NEC) which is accompanied with
      gastrointestinal ulceration and necrosis is one of the most important problems of
      preterm infants in neonatal intensive care unit (NICU). Increased intra-abdominal
      pressure (IAP) is detected among most of the pediatric patients hospitalized in
      intensive care unit and undergoing surgery or trauma. This pathology, namely,
      abdominal compartment syndrome, causes ischemia and hypoperfusion of abdominal
      organs. Recently, the effect of increased IAP on NEC is under focus and this
      increase is thought to be related with the onset of NEC by leading to intestinal
      ischemia and necrosis. In this study, we aimed to investigate if serial
      intravesical pressure (IVP) measurements as an indirect indicator of IAP may help
      to early diagnosis in NEC and to decision for surgery besides to predict the
      mortality of NEC. MATERIAL AND METHOD: A total number of 61 preterm infants with
      a birth weight of <= 1,500 g hospitalized in NICU were included to the study. IVP
      values were measured by the same nurse twice daily during their hospitalization
      through urinary catheter. The IVP values of the preterm infants with and without
      NEC were compared. RESULTS: Totally 61 premature infants included in the study
      were grouped as follows: group 0, the control group without NEC (n = 38); group
      1, medically treated NEC patients (n = 14); and group 2, NEC patients undergoing
      surgery (n = 9). The median IVP measurements of group 0 were lower than the other
      groups (p = 0.001). No statistically significant difference in IVP measurements
      was detected between group 1 and group 2 (p = 0.155). A 10% of increase in IVP
      measurement was significant in predicting the development of NEC with consecutive
      serial measurements. The mean IVP measurements were higher in infants with NEC
      who died during their follow-up at NICU compared with NEC patients who survived
      (p = 0.043). CONCLUSION: Serial IVP measurements may help for early diagnosis and
      surgery decision of NEC and high IVP levels also may predict mortality in cases
      with NEC.

PMID- 23165521
TI  - Matrix and interaction effects on the magnetic properties of Co nanoparticles
      embedded in gold and vanadium.
AB  - The study of the magnetic properties of Co nanoparticles (with an average
      diameter of 10.3 nm) grown using a gas-phase aggregation source and embedded in
      Au and V matrices is presented. We investigate how the matrix, the number of
      embedded nanoparticles (counted by coverage percentage), the interparticle
      interactions and the complex nanoparticles/matrix interface structure define the
      magnetic properties of the studied systems. A threshold coverage of 3.5% of a
      monolayer was found in both studied systems: below this coverage, nanoparticles
      behave as an assembly of independent single-domain magnetic entities with
      uniaxial anisotropy. Above the threshold it is found that the magnetic behavior
      of the systems is more matrix dependent. While magnetic relaxation and Henkel
      plots measurements stress the importance of the dipolar interactions and the
      formation of coherent clusters in the case of the Au matrix, the magnetic
      behavior of cobalt clusters embedded in the vanadium matrix is explained through
      the formation of a spin glass-like state at the V-Co interface that screens the
      magnetic interactions between NPs.

PMID- 23165522
TI  - H. pylori infection and gastric cancer: state of the art (review).
AB  - Gastric cancer (GC) is one of the leading types of cancer worldwide, particularly
      in East Asian populations. Helicobacter pylori (HP) infection has been
      established as a major risk factor for GC. Although more than 50% of the world
      population is infected with this bacterium, less than 2% develop GC. Therefore,
      further risk factors (such as host genetic polymorphisms and lifestyle, as well
      as environmental and epigenetic factors) may also play a role in its occurrence.
      The correlation between HP infection and GC represents a typical model of a multi
      step process, characterized by some pre-neoplastic lesions with a high risk of
      progression (atrophic gastritis, intestinal metaplasia and dysplasia). In
      addition, HP also plays an oncogenic role in the development of mucosa-associated
      lymphoid tissue (MALT) lymphoma, that accounts for approximately 3% of all
      gastric tumors. Hyperplastic polyps often arise in patients with atrophic gastric
      mucosa and HP-associated gastritis (25% of cases); however, their malignant
      transformation is rare (<3% of cases). A number of trials have demonstrated the
      possibility of cancer prevention through HP screening and eradication,
      particularly in high-risk populations, whereas it may not be cost-effective in
      areas of low risk. In this review, we discuss i) the complex pathogenetic
      mechanisms of gastric carcinogenesis in which HP is involved; ii) the main
      approaches to the diagnosis, prevention, surveillance and treatment of pre
      malignant lesions associated with HP infection; iii) the most effective way to
      detect GC in its earlier stages; and iv) the most important contribution to
      reducing the burden of GC.

PMID- 23165523
TI  - Sulfidated TiO2 nanotubes: a potential 3D cathode material for Li-ion micro
      batteries.
AB  - In this work, self-organized titania nanotubes are sulfidated by an annealing
      treatment to produce TiOxSy nanotubes. Morphological, structural and
      electrochemical analyses show that this 3D nanostructured electrode is a
      potential cathode material for Li-ion microbatteries.

PMID- 23165526
TI  - Partial reductions in mechanical loading yield proportional changes in bone
      density, bone architecture, and muscle mass.
AB  - Although the musculoskeletal system is known to be sensitive to changes in its
      mechanical environment, the relationship between functional adaptation and below
      normal mechanical stimuli is not well defined. We investigated bone and muscle
      adaptation to a range of reduced loading using the partial weight suspension
      (PWS) system, in which a two-point harness is used to offload a tunable amount of
      body weight while maintaining quadrupedal locomotion. Skeletally mature female
      C57Bl/6 mice were exposed to partial weight bearing at 20%, 40%, 70%, or 100% of
      body weight for 21 days. A hindlimb unloaded (HLU) group was included for
      comparison in addition to age-matched controls in normal housing. Gait kinematics
      was measured across the full range of weight bearing, and some minor alterations
      in gait from PWS were identified. With PWS, bone and muscle changes were
      generally proportional to the degree of unloading. Specifically, total body and
      hindlimb bone mineral density, calf muscle mass, trabecular bone volume of the
      distal femur, and cortical area of the femur midshaft were all linearly related
      to the degree of unloading. Even a load reduction to 70% of normal weight bearing
      was associated with significant bone deterioration and muscle atrophy. Weight
      bearing at 20% did not lead to better bone outcomes than HLU despite less muscle
      atrophy and presumably greater mechanical stimulus, requiring further
      investigation. These data confirm that the PWS model is highly effective in
      applying controllable, reduced, long-term loading that produces predictable,
      discrete adaptive changes in muscle and bone of the hindlimb.

PMID- 23165528
TI  - Steric and electronic effects on the configurational stability of residual chiral
      phosphorus-centered three-bladed propellers: tris-aryl phosphanes.
AB  - A series of tris-aryl phosphanes, structurally designed to exist as residual
      enantiomers or diastereoisomers, bearing substituents differing in size and
      electronic properties on the aryl rings, were synthesized and characterized.
      Their electronic properties were evaluated on the basis of their electrochemical
      oxidation potential determined by voltammetry. The configurational stability of
      residual phosphanes, evaluated by dynamic HPLC on a chiral stationary phase
      or/and by dynamic (1)H and (31)P NMR spectroscopy, was found to be rather modest
      (barriers of about 18-20 kcal mol(-1)), much lower than that shown by the
      corresponding phosphane oxides (barriers of about 25-29 kcal mol(-1)). For the
      first time, the residual antipodes of a tris-aryl phosphane were isolated in
      enantiopure state and the absolute configuration assigned to them by single
      crystal anomalous X-ray diffraction analysis. In this case, the racemization
      barrier could be calculated also by CD signal decay kinetics. A detailed
      computational investigation was carried out to clarify the helix reversal
      mechanism. Calculations indicated that the low configurational stability of tris
      aryl phosphanes can be attributed to an unexpectedly easy phosphorus pyramidal
      inversion which, depending upon the substituents present on the blades, can occur
      even on the most stable of the four conformers constituting a single residual
      stereoisomer.

PMID- 23165527
TI  - Late outgrowth endothelial cells resemble mature endothelial cells and are not
      derived from bone marrow.
AB  - A decade of research has sought to identify circulating endothelial progenitor
      cells (EPC) in order to harness their potential for cardiovascular regeneration.
      Endothelial outgrowth cells (EOC) most closely fulfil the criteria for an EPC,
      but their origin remains obscure. Our aim was to identify the source and
      precursor of EOC and to assess their regenerative potential compared to mature
      endothelial cells. EOC are readily isolated from umbilical cord blood (6/6
      donors) and peripheral blood mononuclear cells (4/6 donors) but not from bone
      marrow (0/6) or peripheral blood following mobilization with granulocyte-colony
      stimulating factor (0/6 donors). Enrichment and depletion of blood mononuclear
      cells demonstrated that EOC are confined to the CD34(+)CD133(-)CD146(+) cell
      fraction. EOC derived from blood mononuclear cells are indistinguishable from
      mature human umbilical vein endothelial cells (HUVEC) by morphology, surface
      antigen expression, immunohistochemistry, real-time polymerase chain reaction,
      proliferation, and functional assessments. In a subcutaneous sponge model of
      angiogenesis, both EOC and HUVEC contribute to de novo blood vessel formation
      giving rise to a similar number of vessels (7.0 +/- 2.7 vs. 6.6 +/- 3.7 vessels,
      respectively, n = 9). Bone marrow-derived outgrowth cells isolated under the same
      conditions expressed mesenchymal markers rather than endothelial cell markers and
      did not contribute to blood vessels in vivo. In this article, we confirm that EOC
      arise from CD34(+)CD133(-)CD146(+) mononuclear cells and are similar, if not
      identical, to mature endothelial cells. Our findings suggest that EOC do not
      arise from bone marrow and challenge the concept of a bone marrow-derived
      circulating precursor for endothelial cells.

PMID- 23165529
TI  - [Relation of -55CT polymorphism of UCP3 gene with weight loss and metabolic
      changes after a high polyunsaturated fat diet in obese patients].
AB  - BACKGROUND AND OBJECTIVES: The alteration in the protein expression of UCP3 could
      reduce energy consumption and increase energy storage as fat. The aim of our
      study was to investigate the influence of -55CT polymorphism of UCP3 gene in the
      metabolic response, weight loss and serum levels of adipokines following a
      hypocaloric diet rich in polyunsaturated fat in obese patients. DESIGN: A sample
      of 133 obese patients were analyzed prospectively for 3 months. The hypocaloric
      diet was 1459 kcal, 45.7% carbohydrate, 34.4% from 19.9% lipids and proteins. The
      fat distribution was, a 21.8% saturated fat, 55.5% monounsaturated and 22.7% of
      polyunsaturated fat (7 g per day of fatty acids w6, 2 g per day of w -3 and a
      ratio w6/w3 of 3.5). RESULTS: A total of 100 patients (28 males/72 females)
      (75.2%) had genotype - 55CC (wild genotype group) and 33 patients (8 males/25
      females) (24.8%) -55CT genotype (group mutant genotype). In the wild genotype,
      body mass index (-2.5 +/- 5.3 kg/m2), weight (-4.2 +/- 3.7 kg), fat mass (-3,7 +/
      3.3 kg), waist circumference (-4.1 +/- 2.9 cm), systolic blood pressure (-4.9 +/
      10.1 mmHg), total cholesterol levels (- 16.1 +/- 23.6 mg / dl), LDL cholesterol
      (-11.1 +/- 26.8 mg/dl), triglycerides (-12.0 +/- 46.8 mg/dl), insulin (-1.8 +/-
      4.5 IU/L), HOMA-R (-0.6 +/- 1.5) and leptin (-6.2 +/- 8.4 ng/ml) decreased. In
      the mutant genotype anthropometric parameters were significantly decreased
      without significant changes in biochemical parameters. CONCLUSION: The T allele
      carriers of -55CT UCP3 polymorphism exhibit no metabolic response to weight loss
      induced by a hypocaloric diet rich in polyunsaturated fatty acids.

PMID- 23165530
TI  - [The food and nutrition program (1961-1982) and the training of housewives as
      family welfare managers].
AB  - This study provides a gender-based analysis of the Food and Nutrition Education
      Program, developed in Spain over the last decades of the 20th century, to explore
      nutrition education messages and strategies aimed at improving the skills of
      housewives as guardians of family welfare and experts in all areas of household
      management. The Program's specific approach to housewives, and the assumptions on
      which it was based, further entrenched a social model of gender in which men were
      solely responsible for household income and women were family carers.

PMID- 23165531
TI  - [Efectiveness of long-term consumption of nuts, seeds and seeds' oil on glucose
      and lipid levels; systematic review].
AB  - OBJECTIVE: The aim of this study was to determine the effectiveness of long-term
      consumption of nuts, seeds and vegetable oil (NSO) on weight, glucose, and lipid
      levels. METHODS: We searched English articles published in Pubmed and Ebsco up to
      May 2011. Studies were included if they were randomized clinical trials, and had
      an intervention period of 24 or more weeks. Search terms include: "diabetes
      mellitus", "Nuts", "Diet Mediterranean", "Seeds", "Oils", "Canola oil", "Olive
      oil","Walnut", "Almond", "Pistachio", "Paleolithic diet", "High monounsaturated
      diet", "High polyunsaturated diet", "Soya" and "Sunflower". RESULTS: Thirteen
      studies met the inclusion criteria; eight studies had a 24 weeks intervention
      period, one had 42 weeks, one had 48 weeks, and for the other three the
      intervention lasted 52 or more weeks. At 24 weeks a consistent increase of HDL
      levels and inconsistent improvement of weight, BMI, waist to hip index, A1C,
      total cholesterol, LDL: HDL, LDL, triglycerides, and diastolic blood pressure was
      observed. Four studies with an intervention >= 48 weeks showed no statistical
      difference, and in one study a reduction of weight, BMI, waist hip index,
      glucose, insulin, total cholesterol, HDL: cholesterol, triglycerides, and blood
      pressure was observed. CONCLUSION: No evidence of long-term improvement of NSO on
      weight, glucose or lipids in the adult population was found.

PMID- 23165532
TI  - [Relation of serum levels of C-reactive protein to anthropometric meaurements; a
      sustematic review of studies in South America].
AB  - In many studies the Body Mass Index (BMI) is associated with serum markers of
      inflammation such as CRP. In obesity there is an increase of adipose tissue
      resulting in an increase in BMI. It has been reported that adipose tissue has a
      high production and secretion of a variety of proinflammatory molecules such as
      tumor necrosis factor-alpha, interleukin-6, interleukin-8 and C-reactive protein,
      which may have local effects on the physiology of fat cell and systemic effects
      on other organs. OBJECTIVE: To conduct a systematic review of studies conducted
      in South America where they relate serum levels of CRP and anthropometric
      measurements, BMI and waist circumference (CC) in the healthy adult population.
      METHODS: We searched the PubMed database for articles published until January
      2012, in English, Spanish and Portuguese, which relates serum levels of CRP and
      anthropometric measurements, BMI and WC. Search for words used PCR, BMI and WC
      and the names of each of the South American countries (Argentina, Bolivia,
      Brazil, Chile, Colombia, Ecuador, Guyana, Paraguay, Peru, Suriname, Uruguay and
      Venezuela). RESULTS: We identified 141 potential studies, of which 8 met the
      inclusion criteria. In studies serum levels of CRP were positively correlated
      with BMI (r 0.08 to 0.84) and CC (r 0.27 to 1.03), being highly relevant
      correlation between BMI and CC with CRP serum levels observed in obese people in
      South America. CONCLUSION: Serum levels of CRP, and therefore subclinical
      inflammation seems to be related to increased rates of anthropometric measures in
      the South American population. A better understanding of the mechanisms and
      molecular components of the inflammatory response induced by an increase in BMI
      may lead to identifying new therapeutic targets that can prevent the
      complications associated with obesity.

PMID- 23165533
TI  - Role of oleic acid in immune system; mechanism of action; a review.
AB  - INTRODUCTION: Although n-3 polyunsaturated fatty acids have been widely described
      as anti-inflammatory fats, little is known about the role of oleic acid in immune
      system. AIM: The aim of the present review is to join all the reports available
      in order to analyze where exactly the knowledge concerning this topic is and what
      the causes of the controversial data could be. METHODS: We searched electronic
      databases and bibliographies of selected articles were inspected for further
      reference. RESULTS: Diets rich in oleic acid have beneficial effects in
      inflammatory-related diseases. In addition, a wide range of studies evaluate the
      effect of oleic acid in different cellular functions thus reporting a potential
      mechanism for the biological effect of such a fat. However, some controversial
      data can be found in literature, maybe related to the kind of study or even the
      dose of the reagent added. CONCLUSION: In conclusion, oleic acid could be
      reported as an anti-inflammatory fatty acid playing a role in the activation of
      different pathways of immune competent cells.

PMID- 23165534
TI  - Possible molecular mechanisms soy-mediated in preventing and treating
      nonalcoholic fatty liver disease.
AB  - The aim of this review is to describe the molecular mechanisms of nonalcoholic
      fatty liver disease (NAFLD) and to present evidence regarding the mechanisms of
      soy-mediated therapeutic activity in preventing and treating NAFLD. NAFLD is
      induced by multiple metabolic pathways, including an increase in the release of
      fatty acids from the adipose tissue (lipolysis), insulin resistance (IR), and an
      increase in "de novo" fatty acid synthesis. Furthermore, NAFLD is correlated with
      a decrease in liver beta-oxidation, an increase in oxygen free radical
      production, and an increase in pro-inflammatory cytokine production, which leads
      to an increase in liver fat and, subsequently, to tissue damage. The bioactive
      compounds in soy can prevent and treat NAFLD by modulating lipid metabolism and
      regulating the expression of related transcription factors. Soy intake decreases
      the expression of sterol regulatory-element binding protein-lc (SREBP-1) and
      increases the expression of SREBP-2, which are transcription factors associated
      with the regulation of hepatic lipogenesis and reduction of cholesterol synthesis
      and absorption in the liver, respectively. Besides, interactions between soy
      components, such as standard amino acids, polyunsaturated fat, and the
      isoflavonoid-enriched fraction, are believed to improve fatty acid oxidation in
      the liver parenchyma by increasing the expression of peroxisome proliferator
      activated receptor alpha (PPARalpha)-regulated genes, thus decreasing lipid
      accumulation in the liver. Therefore, including soy-derived foods in the diet as
      a therapeutic tool for patients with NAFLD might improve their clinical
      evolution.

PMID- 23165535
TI  - Enteral nutrition therapy for critically ill adult patients; critical review and
      algorithm creation.
AB  - INTRODUCTION: Undernutrition directly affects critically ill patient's clinical
      outcome and mortality rates. OBJECTIVE: Interdisciplinar algorithm creation
      aiming to optimize the enteral nutrition therapy for critically ill adult
      patients. DATA SOURCE: Pubmed, SciELO, Scholar Google, Web of Science, Scopus,
      with research of these key words: protocols, enteral nutrition, nutritional
      support, critical care, undernutrition, fasting. SETTING: Intensive Care Unit,
      Hospital de Clinicas, Federal University of Uberlandia, MG, Brazil. MEASUREMENTS
      AND MAIN RESULTS: Were established in the algorithm a following sequential steps:
      After a clinical-surgical diagnosis, including the assessment of hemodynamic
      stability, were requested passage of a feeding tube in post-pyloric position and
      a drainage tube in gastric position. After hemodynamic stability it should be
      done the nutritional status diagnosis, calculated nutritional requirements, as
      well as chosen formulation of enteral feeding. Unless contraindicated, aiming to
      increase tolerance was started infusion with small volumes (15 ml/h) of a semi
      elemental diet, normocaloric, hypolipidic (also hyperproteic, with addition of
      glutamine). To ensure infusion of the diet, as well as the progressive increase
      of infusion rates, the patient was monitored for moderate or severe intestinal
      intolerance. The schedule and infusion rates were respected and diet was not
      routinely suspended for procedures and diagnostic tests, unless indicated by the
      medical team. CONCLUSIONS: For nutrition therapy success it is essential routine
      monitoring and extensive interaction between the professionals involved.
      Nutritional conducts should be reevaluated and improved, seeking complete and
      specialized care to the critically ill patients. Adherence to new practices is
      challenging, though instruments such as protocols and algorithms help making
      information more accessible and comprehensible.

PMID- 23165536
TI  - Chemical composition, antioxidant capacity and content of phenolic compounds in
      meals collected in hospitals in Bolivia and Sweden.
AB  - The objective of this study was to evaluate the proximal composition, as well as
      Total Antioxidant Capacity (TAC) and Total Phenols (TPH) in meals that represent
      a complex food matrix, from different hospitals in Bolivia and Sweden. Protein,
      fat, ash, dietary fiber and carbohydrate contents were measured in 29 samples: 20
      from two Bolivian hospitals and 9 from the university hospital in Lund, Sweden.
      The antioxidant capacity was measured by three spectrophotometric methods: the
      ferric reducing antioxidant power (FRAP) method, the 2, 2'- azinobis-3
      ethylbenzotiazoline-6-sulfonic acid (ABTS) method and Total Phenolic Compounds
      (TPH) using the Folin-Ciocalteu reagent. The results show that fat, protein,
      carbohydrate and dietary fiber in Bolivian and Swedish hospital meals are
      following internationally established recommendations. Regarding the main
      courses, TPH contents in both countries were in the same range. However, TAC and
      dietary fiber content were higher in Swedish meals than in Bolivian meals and the
      TAC was far lower, in both cases, in comparison with the value obtained from
      individual food items reported from literature. The results show that antioxidant
      levels can be easily overestimated by considering only individual uncooked
      ingredients. An interesting consideration is, the fiber content in the meals,
      which can be an important source of antioxidants and non-extractable phenolic
      compounds.

PMID- 23165537
TI  - Mushrooms of the genus Agaricus as functional foods.
AB  - Mushrooms of the genus Agaricus are noted for their pharmacological and culinary
      properties. In this study, it was performed a critical literature review,
      focusing primarily on aspects of the chemical composition of these mushrooms
      whose pharmacological properties and nutritional composition characterize them as
      functional foods. It was also discussed articles conducted in vitro and in vivo
      proving the high antioxidant potential of the Agaricaceae family, in addition to
      articles which emphasize the toxicity characteristics and safety for its use in
      therapy or in human nutrition. These mushrooms exhibit numerous bioactive
      substances as well as safety regarding toxicity, which characterize them as
      functional foods. Despite the countless beneficial effects on human health,
      mushrooms of the genus Agaricus are little known by the population, making it
      necessary partnership and combined efforts among producers, industries and
      researchers in order to disseminate, research and consumption of these foods.

PMID- 23165538
TI  - [Minimally invasive emergent techniques in obesity treatment].
AB  - INTRODUCTION: Obesity is a chronic disease for which several modalities of
      treatment are investigated today. One of them is the set of minimally aggressive
      techniques that have been added to the intragastric balloon. OBJECTIVE: To review
      the minimally invasive techniques described in the last years for the treatment
      of obesity. MATERIAL AND METHOD: It consisted in reviewing the bibliography
      through the habitual finders, in addition to the obtained data of the companies.
      They are classified in restrictive and malabsortive, and the restrictive are
      divides in mechanical or functional restriction. RESULT: Between mechanical
      restrictive the classified as we included in the restrictive emergent techniques
      the adjustable intragastric balloon, the intragastric prosthesis, the vertical
      endoluminal gastroplasty and the transoral gastroplasty. In order to obtain a
      functional restriction, we have the gastric pacemaker and the botulinic toxin.
      And finally, the endoluminal duodenojejunal bypass is described as a malabsortive
      technique. DISCUSSION: With less than 10 years of existence, it seems that the
      described techniques compensate their smaller effectiveness compared to the
      surgical techniques, with the absence of substantial modifications in the anatomy
      of the alimentary tract. None of these techniques is free of risks and
      complications.

PMID- 23165539
TI  - [Food and diabetes].
AB  - A low glycemic diet may improve metabolic control in type 2 diabetes, but the
      debate continues. Fruits, despite the fructose they contain, may also lower the
      glycemic index, as well as its consumption has been associated with a reduction
      in A1c levels and can positively influence HDL cholesterol, blood pressure and
      risk of coronary heart disease in general. There is no relationship between fat
      intake and A1c. On the consumption of alcohol has been reported that moderate
      alcohol consumption is associated with a lower prevalence of metabolic syndrome,
      although there is information that relates to the A1c. This article reviews the
      published evidence on the effect of consumption of fruits, fats and alcohol on
      metabolic control in diabetics.

PMID- 23165540
TI  - [Prebiotics and nucleotides in infant nutrition; review of the evidence].
AB  - INTRODUCTION: Most of the initiation and maintenance pediatric formulas
      commercialized in Spain contain prebiotics and/or nucleotides aiming at achieving
      beneficial effects on prevention of different pathologies and immune protection,
      similar to human breast milk. However, according to the current legislation, its
      inclusion is optional since sufficient scientific evidences supporting its
      mandatory inclusion is lacking. OBJECTIVE: To systematically review the
      scientific evidence from randomized clinical studies with a control group
      allowing determining the beneficial role for infant health derived from the
      inclusion of prebiotics and/or nucleotides in pediatric formulas. METHODOLOGY: We
      looked for and selected both original papers and reviews in Spanish and English
      language of placebo controlled randomized clinical studies published in the
      databases MEDLINE/PubMed, Scielo, Science Direct, and Scopus, until October of
      2011. RESULTS: We found 43 randomized clinical trials meeting the inclusion
      criteria. CONCLUSIONS: More long-term randomized studies with higher number of
      patients, and standardized supplemental amounts and experimental conditions are
      needed to establish healthy statements with stronger scientific support regarding
      the addition of a mixture of prebiotics (GOS/FOS) and/or nucleotides in pediatric
      formulas. The current trend to include them in pediatric formulas may be
      justified based on the currently available evidence, as well as their safety and
      their presence in human breast milk.

PMID- 23165541
TI  - Prevalence and costs of malnutrition in hospitalized patients; the PREDyCES
      Study.
AB  - BACKGROUND AND AIMS: The main objective of the PREDyCES study was twofold. First,
      to analyse the prevalence of hospital malnutrition in Spain, both at admission
      and at discharge, and second, to estimate the hospital costs associated with
      disease-related malnutrition. METHODS: The study was a nationwide, cross
      sectional, observational, multicentre study in routine clinical practice, which
      assessed the prevalence of hospital malnutrition both at patient admission and
      discharge using NRS-2002. A study extension analysed the incidence of
      complications associated with malnutrition, excess hospital stay and healthcare
      costs associated with hospital malnutrition. RESULTS: Malnutrition was observed
      in 23.7% of patients according to NRS-2002. Multivariate analysis revealed that
      age, gender, presence of malignant disease, diabetes mellitus, dysphagia and
      polymedication were the main factors associated with the presence of
      malnutrition. Malnutrition was associated with an increase in length of hospital
      stay, especially in patients admitted without malnutrition but who presented
      malnutrition at discharge (15.2 vs. 8.0 days, p < 0.001), with an associated
      additional cost of ?5,829 per patient. CONCLUSION: In Spanish hospitals, almost
      one in four patients is malnourished. This condition is associated with increased
      length of hospital stay and associated costs, especially in patients developing
      malnutrition during hospitalization. Systematic screening for malnutrition should
      be generalised in order to implement nutritional interventions with well-known
      effectiveness.

PMID- 23165542
TI  - [Aging and hyponutrition; a challenge for the sustainability of the NHS.
      Conclusions of the 9th ABBOT-SENPE Debate Forum].
AB  - Hyponutrition is a common problem at all health care levels, from primary to
      specialized care, as well as in geriatric care. Its incidence in a hospital
      setting is 40% and 60% in nursing homes. This is very important, it is highly
      related with progressive aging of the European population, and is the biggest and
      most frequent cause of disability among the elderly population living at home or
      institutions. Countries such as Holland, Denmark, or the United Kingdom have
      developed Comprehensive Strategic Plans to fight against hyponutrition by
      developing and implementing guidelines, establishing mandatory screenings at the
      moment of hospital admission and discharge, at nursing homes, etc. In our
      country, a combined action of SENPE and Abbott Foundation is developing a
      Comprehensive Strategic Plan (+ nutridos Project) in which clear, precise, and
      validated recommendations are established to perform nutritional screening both
      in hospitalized patients and institutionalized and ambulatory elderly people.
      This issue has to take into account the social and financial aspects.
      Hyponutrition is many times insufficiently recognized and treated. This has a
      negative impact on the individual patient in terms of morbidity, mortality,
      independence, and quality of life, as well as on the health care systems in terms
      of use of health care resources and costs.

PMID- 23165543
TI  - [Nutricional adequacy of students of compulsory secondary education in Badajoz].
AB  - OBJECTIVE: To evaluate nutricional adequacy of students of compulsory secondary
      education (ESO) in Badajoz, Spain. METHODS: We included 1197 students of ESO from
      12 to 18 years old, 49.9% male and 50.1% female, which is a representative sample
      of this population. They filled in a food frequency questionnaire (FFQ) self
      administered and previously validated in a pilot study. Nutrients were quantified
      from FFQ with a food composition table (Novartis, 2004) and nutritional Adequacy
      Index (AI) was calculated according to Spanish Recommended Dietary Allowances
      (RDA). Nutritional adequacy of a nutrient was measured by the following relation:
      mean daily intake of the nutrient / RDA of that nutrient * 100. RESULTS: Average
      caloric intake of secondary education students is not very high, protein AI is
      over 200%, and cholesterol over 150%, being appropriate the intake of
      carbohydrates and lipids. The intake of fiber, vitamin E and iodine was lower
      than 50% in both genders; the one of iron less than 90% in females and there were
      no other differences between both genders. Only 1% to 3% of students reach RDA of
      fiber, iodine and vitamin E, and 37.3% of female reach RDA of iron. Cholesterol
      dietary intake of 17.2% males and 25.3% females is high, and saturated fatty
      acids intake is high in 46.1% males and 50.0% females. CONCLUSIONS: Diet of
      students of secondary education in Badajoz is normocaloric, hyperproteic,
      appropriate in carbohydrates and lipids, without differences between genders; it
      is very deficient in fiber, iodine and vitamin E in both genders and deficient in
      iron in females. We can see their diet is far from Mediterranean diet, and this
      is why education plans about food intake are advised to the students and their
      families.

PMID- 23165544
TI  - Eating style, television viewing and snacking in pre-adolescent children.
AB  - INTRODUCTION: Television viewing is considered to be a risk factor for overweight
      in children because of its association with reduced physical activity and
      increased calorie intake. OBJECTIVE: The aim of the present study is to examine
      whether eating styles affect the relationship between television viewing (TV
      viewing) and snacking. METHOD: In a sample of 962 pre-adolescents, self-reported
      television viewing and snacking were assessed in relation to dietary restraint,
      external eating and emotional eating, as measured with the child version of the
      Dutch Eating Behavior Questionnaire. With regression analyses we assessed the
      possible moderating role of emotional, external and restrained eating on the
      relation between TV-viewing and snacking. In all analyses we controlled for age,
      sex, BMI and the possible confounding effects of the other eating styles.
      RESULTS: Emotional eating, and not dietary restraint or external eating,
      moderated the relationship between TV-viewing and snacking. CONCLUSION: TV
      viewing seems to be more strongly related to snacking in children with higher
      levels of emotional eating. TV-viewing may also be a risk factor for the
      development of emotional eating.

PMID- 23165545
TI  - [Methods of body composition and four compartiments model in obese school
      children].
AB  - INTRODUCTION: In Chile, the prevalence of obesity in schoolchildren is 21.3%. The
      study and individual intervention of this malnutrition, it is necessary to have
      not only global indicators of nutritional status, but also indicators that give
      information on body composition. OBJECTIVE: To compare estimates of body fat
      isotopic dilution, plethysmography and radiographic absorptiometry 4C model in
      overweight schoolchildren. METHODS: We worked with 61 obese (BMI >= p 95) of both
      sexes, between 8 and 13 years, enrolled in a school in a district of the city of
      Santiago. The multicompartmental body composition determination, considered
      isotopic dilution, plethysmography and radiographic absorptiometry. Using as a
      reference standard four compartment model of Fuller. RESULTS: In both sexes, the
      method showed better agreement with the reference of 4 compartments was isotope
      dilution (r = 0.98, p < 0.01). In children, the isotopic dilution underestimates
      body fat in -0.40 kg. By contrast, DEXA and plethysmography overestimate body fat
      by 0.81 kg and 1.89 kg respectively. In women, all methods overestimate body fat,
      with less emphasis isotopic dilution value 0.46 kg, 0.52 kg after DEXA and
      plethysmography 1.31 kg. CONCLUSIONS: The deuterium isotopic dilution would be
      the most sensitive method for estimating body fat in research studies because it
      shows the best agreement with the gold standard multicompartmental model.

PMID- 23165546
TI  - Nutritional risk and status of surgical patients; the relevance of nutrition
      training of medical students.
AB  - BACKGROUND: The prevalence of undernutrition among surgical patients is thought
      to be high, and negatively influencing outcomes. However, recent evidence shows
      the increase of overweight/obesity in hospitalised patients. AIMS: A pilot cross
      sectional study was conducted in 50 patients of a Surgical Department of the
      University Hospital of Santa Maria (CHLN) that aimed: 1) to assess nutritional
      risk and status through validated methods; 2) to explore the presence of
      overweight/obesity; 3) to evaluate the prevalence of metabolic risk associated
      with obesity. METHODS: Nutritional risk was assessed by Malnutrition Universal
      Screening Tool (MUST), nutritional status by Body Mass Index (BMI), waist
      circumference (WC), & Subjective Global Assessment (SGA). Statistical
      significance was set for p < 0.05. RESULTS: 58% of patients were overweight/obese
      and 54% had high cardio-metabolic risk, according to waist circumference; 30% of
      patients had significantly lost weight (>= 5%), whereas 28% gained weight. By
      MUST, 46% of patients were at low risk and 34% at high risk. By SGA, 58% patients
      were well nourished and 40% had moderate/severe undernutrition. A longer length
      of stay was associated with moderate/high risk by MUST, and undernutrition by SGA
      (p = 0.01). CONCLUSIONS: Undernutrition or obesity pose surgical risks. The lack
      of nutrition discipline in the medical curricula, limits the multiprofessional
      management and a better understanding of the more adequate approaches to these
      patients. Further, the change in the clinical scenario argues for more studies to
      clarify the prevalence and consequences of sarcopenic obesity in surgical
      patients.

PMID- 23165547
TI  - [Folate status in Spanish schoolchildren and its association with parental
      smoking habits].
AB  - AIM: To study the folate status in a group of Spanish schoolchildren and its
      association with parental smoking habits. METHODS: A group of 511 schoolchildren
      between 9 and 12 years old from Madrid (Spain) were studied. Parental smoking
      habits were self-reported by a questionnaire. Energy and nutrients intake
      (especially folates) were calculated with a "3-day diet record" and during two
      days (Monday and Tuesday) the food consumption was controlled in the school
      canteen using the "precise weighing method" (recording the weights of food served
      and leftovers on the plate). Folate intake of the sample was compared with the
      recommended intakes (RI) for this vitamin. Folate, vitamin B12 and homocysteine
      were determined. Student's t-test, Mann Whitney Test, Pearson and Spearman
      correlation, ANCOVA, MANCOVA and multiple linear regression were applied for
      statistical analysis. Significance was set at P < 0.05. RESULTS: Vegetable and
      fruit consumption, folate intake and its coverage to recommended folate intake
      (I/RI%) and serum folate levels were higher in children of nonsmoking mothers
      than in children of smoking mothers. Serum folate level in 13.3% of the children
      studied was below 6 ng/mL (moderate deficit), and in 0.26% was below 3 ng/mL
      (severe deficit). Taking into account others confounding factors a negative and
      significant correlation was observed between serum folate levels of children and
      smoking habits in mothers (r = -0.257, p = 0.01). CONCLUSION: The maternal
      smoking habits might determine folate intake and serum folate levels on their
      offspring.

PMID- 23165548
TI  - Nutritional status and adequacy of enteral nutrition in pediatric cancer patients
      at a reference center in northeastern Brazil.
AB  - INTRODUCTION: Individualized nutritional support is important to pediatric cancer
      patients and should be integrated to the overall treatment of these patients.
      OBJECTIVE: Analyze the nutritional status of cancer patients submitted to enteral
      nutrition (EN) and assess the adequacy of this form of nutrition. METHODS: A case
      series study was carried out at the Pediatric Oncology Unit of the Institute of
      Integrative Medicine Professor Fernando Figueira (IMIP, Brazil, Recife-PE)
      between January and December 2009. Clinical and anthropometric data were obtained
      from medical charts and nutritional follow-up charts. Z scores for height for
      age, weight for age and body mass index for age indicators (H/A, W/A and BMI/A,
      respectively) were calculated using the AnthroPlus program. Caloric and protein
      requirements were calculated based on the recommendations of the Brazilian
      National Council of Oncologic Nutrition. RESULTS: At the beginning of EN, 32.4%
      of the sample had short stature and 23.9% were underweight based on the BMI/A
      indicator. The assessment of EN adequacy demonstrated that 49.3% reached the
      caloric requirements and 76.1% reached the protein requirements, with maximal
      intakes of 65.6 Kcal/Kg/day and 1.95 g of protein/kg/day. Malnourished patients
      had greater mean Z scores for W/A and BMI/A at the end of EN, whereas no
      significant changes were found among patients with adequate nutritional status
      and significant reductions in these indicators were found among those with
      overweight or obesity. CONCLUSION: The patients either maintained or achieved a
      significant improvement in nutritional status, which demonstrates the importance
      of nutritional support and follow up during hospitalization.

PMID- 23165549
TI  - [Anthropometric study and evaluation of the nutritional status of a population
      school children in Granada; comparison of national and international reference
      standards].
AB  - Recent studies show an alarming increase in levels of overweight and obesity
      among children and adolescents. The main objectives of this research were the
      following: (i) to carry out an anthropometric evaluation of the nutritional
      status and body composition of school children in the city and province of
      Granada; (ii) to compare the nutritional status of this population sample with
      national and international reference standards. The results obtained in this
      study showed that the general prevalence of overweight in both sexes was 22.03%
      and that 9.12% of the children were obese. Statistically significant differences
      were found between the variable, weight for age and sex (p < 0.05) and the
      variable, height for age and sex (p < 0.05). Regarding the body mass index, no
      statistically significant differences were found for the variable, sex (p =
      0.182). This contrasted with the variable, age, which did show statistically
      significant differences (p < 0.05). As a conclusion, the results of our study
      highlighted the fact that these anthropometric values were much higher than
      national and international reference standards.

PMID- 23165550
TI  - Validation of a food frequency questionnaire for children and adolescents aged 4
      to 11 years living in Salvador, Bahia.
AB  - OBJECTIVE: To assess the validity of a food frequency questionnaire (FFQ) by
      applying it to children and adolescents living in Salvador, Bahia. METHODS: The
      validity of this FFQ with 98 food items was investigated among 108 children and
      adolescents who were selected from a sample of 1445 that had been planned for a
      study on the risk factors for asthma and other allergic diseases. The adults
      responsible for these children and adolescents gave responses for a 24-hour
      recall (R24h) and an FFQ. The average energy and nutrient values from the FFQ
      were compared with those from the R24h by means of the paired t test and Pearson
      correlation coefficients. The concordance was evaluated using the Bland-Altman
      method and kappa statistics. RESULTS: The energy and nutrient intake estimated
      using the FFQ was significantly higher than what was obtained using the R24h. The
      correlation coefficients adjusted for energy were statistically significant for
      protein, fat, vitamin C and zinc. The weighted kappa values ranged from 0.06 for
      vitamin A (p = 0.24) to 0.34 for energy (p < 0.00). The results from the Bland
      Altman plots for lipid, protein and zinc showed the most significant validity
      parameters, and zinc was found to show the best concordance. CONCLUSION: The
      results suggest that the FFQ showed satisfactory validity for use in studies
      involving children and adolescents.

PMID- 23165551
TI  - [Delay in the acquisition of sucking-swallowing-breathing in the preterm; efects
      of early stimulation].
AB  - INTRODUCTION: Premature baby's oral feeding is not possible until the reflex of
      sucking-swallowing-breathing adquisition. Its delay extends hospital stay and
      increases the incidence of oral motor disorders in early childhood. AIMS: To
      analyze the transition from enteral to oral nutrition, the comorbidity associated
      with its delay and the impact of an early suction stimulation in a cohort of
      premature babies. PATIENTS AND METHODS: Retrospective checking of 95 infants less
      than 32 gestation weeks (GW) admitted to a neonatal ICU in the last 4 years. It
      was revised the gestational age, anthropometric at birth and discharge,
      comorbidity, duration of mechanical ventilation, oxygen requirements, time of
      beginning and end of enteral/oral nutrition, beginning of Kangaroo method and the
      suction stimulation and the daily weight gain average. RESULTS: Suction
      stimulation began between weeks 29 and 40 GW (average and median 32 GW). Oral
      nutrition was initiated between 31-40 GW (average and median 33 GW) and completed
      between 33-44 GW (average and median 35 GW). Oral nutrition was delayed in
      patients who required longer mechanical ventilation and oxygen therapy. There was
      a positive correlation between the beginning of suction stimulation and the time
      of acquisition of a complete oral nutrition (84% Spearman correlation test) and
      length of hospital stay (80% Spearman correlation test). CONCLUSIONS: [corrected]
      Early suction stimulation in a preterm patient seems to facilitate full oral
      nutrition at an early stage and it is associated with a hospital stay decrease
      and the improvement in the daily weight gain average.

PMID- 23165552
TI  - Comparison of the biochemical, anthropometric and body composition variables
      between adolescents from 10 to 13 years old and their parents.
AB  - OBJECTIVE: The present study had the objective of comparing the lipid profile,
      nutritional status and body composition of adolescents and their parents.
      METHODS: A cross-sectional study was conducted with 120 adolescents from 10 to 13
      years old, public schools students from the city of Vicosa, Minas Gerais, Brazil
      and their respective biological parents (104 mothers and 82 fathers). Data was
      collected regarding weight, height, waist and hip circumference, body fat,
      triglycerides, total and fraction cholesterol. Besides, taking the skinfold
      measurements (bicipital, tricipital, subscapular and suprailiac) of the
      adolescents; and evaluation of sexual maturity, excluding those that were in
      stage 1 according to Tanner. The statistical treatment includes descriptive
      analysis, the use of the Student's t-test, Mann Whitney, and Pearson and Spearman
      correlation. An Odds Ratio was conducted with a confidence interval of 95%,
      considering p < 0.05 significant. RESULTS: A positive and significant correlation
      was seen for weight, BMI and total cholesterol between father and son; for all
      the variables, except body fat and wait/hip ratio between father and daughter;
      for weight and height between mother and son and BMI between mother and daughter.
      Adolescents that had both parents with hypertriglyceridemia, with inadequacies of
      LDL or HDL presented, respectively 19, 20 and 4 times more chances of presenting
      the same alterations. CONCLUSION: This study confirmed differences in the
      anthropometric measurements, body composition and lipid profile between children
      of overweight, eutrophic and underweight parents, as well as greater chance for
      the adolescent to present an altered lipid profile when the parents also have
      presented that alteration.

PMID- 23165553
TI  - Evolution of nutritional, hematologic and biochemical changes in obese women
      during 8 weeks after Roux-en-Y gastric bypasss.
AB  - Obesity is a chronic disease of multifactorial origin and currently is a serious
      public health problem. The treatment of morbid obesity can be effectively done by
      bariatric surgery. The present study aimed to evaluate the influence of changes
      in food intake on body composition and some hematologic and biochemical variables
      in the period of eight weeks after Roux-en-Y gastric bypass (RYGB). The study
      included 22 women submitted to RYGB. We evaluated anthropometric, nutritional,
      hematologic and biochemical variables before and 14, 28, 42 and 56 days after
      surgery. The patients showed a decrease in caloric intake and hence macro- and
      micronutrients, with significant loss of weight and decrease in body mass index
      (BMI). Decreases in body weight and BMI were associated with reduced blood levels
      of total cholesterol, VLDL-C, LDL-C, triglycerides and glucose with time after
      surgery. The decrease in caloric intake was also associated with decreased intake
      of protein, iron and calcium, with a decline in hemoglobin, hematocrit and red
      blood count, and RDW increased after surgery.

PMID- 23165554
TI  - Group dialectical behavior therapy adapted for obese emotional eaters; a pilot
      study.
AB  - Dialectical Behavior Therapy (DBT) has been shown to effectively target binge
      eating disorder (BED). This study pilots the effectiveness of group DBT for obese
      "emotional eaters" to reduce eating psychopathology and achieve weight
      maintenance. Thirty-five obese male and female emotional eaters receiving 20
      group psychotherapy sessions of DBT adapted for emotional eating were assessed at
      end-of-treatment and 6 month follow-up for reductions in eating psychopathology
      and weight maintenance. DBT resulted in significant reductions in emotional
      eating and other markers of eating psychopathology at the end-of-treatment that
      were maintained at follow-up. The drop-out rate was very low, with only 1
      participant dropping from treatment. Thirty-three (94%) of the sample provided
      data at every assessment point. Of these, 80% achieved either weight reduction or
      weight maintenance after treatment and throughout the follow-up period. The
      effect size for weight reduction was small. This pilot study demonstrates group
      DBT targeting emotional eating in the obese to be a highly acceptable and
      effective intervention for reducing eating related psychopathology at both at end
      of-treatment and during follow-up. The ability of DBT to limit the upward
      trajectory of weight gain in obese patients with high degrees of emotional eating
      suggests that DBT may also help limit the increase or even prevent onset of
      obesity related morbidity in these patients.

PMID- 23165555
TI  - [From fear of obesity to the obsesion with thinness; attitudes and diet].
AB  - OBJECTIVE: Investigate the relationship between body satisfaction, attitudes
      toward body and obesity, diet quality and emotional health in a group of
      university students. The initial hypothesis was that attitudes to thinness and
      fear of obesity induces weight control behaviours and lower diet quality.
      METHODS: 55 women of 19-25 years. The relationship between body mass index (BMI),
      diet quality (DQ), restrictive behaviours, eating attitudes (EDI-2, CIMEC) and
      attitudes toward obesity (AFA) was analyzed. Measures of health (SF-12) and
      emotional state (PNA) were also collected. RESULTS: 10.9% of the sample had a
      diet classified as "poor", 83.6% "needs improvement" and 5.5% followed a "good"
      diet. Most of participants were dissatisfied with their weight even when their
      BMI was located in the normal range. Weight-restrictive behaviors were associated
      with risk attitudes to eating disorders, but DQ did not discriminate among high
      and low BMI groups, nor was related to attitudes. The more was the anxiety
      (negative affect), the more were the body dissatisfaction and pressures on body
      image. Idealized social image of thinness was linked to the stigmatization of
      obesity, lower dietary diversity and more restrictive practices. CONCLUSION: The
      results of this pilot study contributes to clarify the relationship between
      psychological and behavioral indices related to diet in university women
      students.

PMID- 23165556
TI  - [Obesity and seric levels of strogens; the importance of early development of
      breast cancer].
AB  - Many studies have analyzed the possible association between the development of
      obesity and hormone levels, as well as their relation with the early development
      of breast cancer. As part of this study, we performed a retrospective collection
      of data from the clinical histories of 524 women in Granada (Spain), who had been
      diagnosed with breast cancer. The objectives were to verify an association
      between the nutritional state of the women and their age at breast cancer
      diagnosis as well as a possible relation between their nutritional state and
      seric levels of estrogens. The results obtained in this study show that obesity
      and the levels of certain hormones, such as estrogens, are closely associated
      with the early development of breast cancer.

PMID- 23165557
TI  - [Roux-en-Y gastric bypass for treatment of patients with DM type 2 and BMI of 30
      to 35 Kg/m2].
AB  - BACKGROUND: The incidence of obesity and its most feared comorbidity, diabetes
      mellitus type 2, is increasing and there would not seem to be any medical
      treatment to help control these pandemics. However, there is a bariatric surgery
      technique, the Roux-en-Y Gastric Bypass (RYGB), which is safe and not only helps
      control excess weight, but produces encouraging results in the control and
      remission of diabetes. METHODS: We present 15 selected patients with a BMI
      between 30 and 35 kg/mt2 and diabetes type 2 who underwent a laparoscopic RYGB
      with of one-year follow-up. RESULTS: A total of 14 women and one man were
      operated with the following average values: age: 37 years, weight: 88.3 kg, BMI:
      32.8 kg/mt2, blood glucose: 120 +/- 38.8 mg%, HbA1c: 7.6 +/- 0.73. Forty percent
      (40%) suffered from high blood pressure and 33.3% were dyslipidemic. Average
      surgical time was 75 minutes, hospital length of stay was two days, and there was
      a low rate of complications and no mortality. Diabetes remission was achieved in
      93% of cases with significant drops in blood glucose and HbA1c (p <= 0.05 and p
      <= 0.001 respectively), dyslipidemia was 100% controlled and hypertension was
      83.3% controlled. CONCLUSIONS: RYGB in selected patients with obesity type 1 and
      diabetes mellitus type 2 is a safe and effective technique for metabolic control
      and obesity control.

PMID- 23165558
TI  - [Overweight and obesity as a prognosis factor of desmotivation in children and
      adolescents].
AB  - Spain has become the country in the European Union with the fourth highest number
      of overweight and obese children. This condition directly affects physical health
      as well as mental health. The objective of this research study was to evaluate
      motivational aspects in one group of obese or overweight adolescents and another
      group of normal-weight adolescents. For this purpose a descriptive observational
      study was carried out in an educational institution in Guadix (Granada). The
      universe was composed of 200 children of ages 10 to 14. A sample of 24 children
      was selected by means of proportional random sampling with an error of 0.19, and
      was divided into the following groups (i) 12 normal-weight children; (ii) 12
      obese children. Motivation was measured by means of the School Motivation
      Analysis Test (SMAT), a multidimensional measuring instrument based on Cattell's
      dynamic model of motivation and emotions. Our study evaluated five motivational
      parameters: TAO (total autism-optimism), TGI (total general information), TIN
      (total integration), TPI (total personal interest), and TCO (total conflict). Our
      results showed that for each of the SMAT variables, the overweight and obese
      children obtained an average value of 4.5 in contrast to the normal-weight
      children, who obtained an average value of 5.9. This indicates that overweight
      and obese children have low motivational states and a higher level of
      frustration. They also tend to distort reality by alleging the existence of
      obstacles that prevent them from achieving their goals.

PMID- 23165559
TI  - Qualifying instrument for evaluation of food and nutritional care in hospital.
AB  - Establishing criteria for hospital nutrition care ensures that quality care is
      delivered to patients. The responsibility of the Hospital Food and Nutrition
      Service (HFNS) is not always well defined, despite efforts to establish
      guidelines for patient clinical nutrition practice. This study describes the
      elaboration of an Instrument for Evaluation of Food and Nutritional Care (IEFNC)
      aimed at directing the actions of the Hospital Food and Nutrition Service. This
      instrument was qualified by means of a comparative analysis of the categories
      related to hospital food and nutritional care, published in the literature.
      Elaboration of the IEFNC comprised the following stages: (a) a survey of
      databases and documents for selection of the categories to be used in nutrition
      care evaluation, (b) a study of the institutional procedures for nutrition
      practice at two Brazilian hospitals, in order to provide a description of the
      sequence of actions that should be taken by the HFNS as well as other services
      participating in nutrition care, (c) design of the IEFNC based on the categories
      published in the literature, adapted to the sequence of actions observed in the
      routines of the hospitals under study, (d) application of the questionnaire at
      two different hospitals that was mentioned in the item (b), in order to assess
      the time spent on its application, the difficulties in phrasing the questions,
      and the coverage of the instrument, and (e) finalization of the instrument. The
      IEFNC consists of 50 open and closed questions on two areas of food and
      nutritional care in hospital: inpatient nutritional care and food service
      quality. It deals with the characterization and structure of hospitals and their
      HFNS, the actions concerning the patients' nutritional evaluation and monitoring,
      the meal production system, and the hospital diets. "This questionnaire is a tool
      that can be seen as a portrait of the structure and characteristics of the HFNS
      and its performance in clinical and meal management dietitian activities."

PMID- 23165560
TI  - The consumption of low glycemic meals reduces abdominal obesity in subjects with
      excess body weight.
AB  - OBJECTIVE: To evaluate the effect of the glycemic index (GI) on food intake,
      anthropometric measurements and body composition in subjects with excess body
      weight. METHODS: Crossover study, in which 17 subjects participated in two study
      sessions (high GI or low GI). Two daily meals were consumed in laboratory for 30
      consecutive days in each session. Subjects also consumed under free living
      conditions 3 daily isocaloric servings of fruits, presenting the same GI as the
      session in which they were participating. At each 15 days, subjects were
      submitted to body composition (lean mass and fatty mass) and anthropometric
      indexes (weight, height, body mass index, waist circumference (WC), hip
      circumference, hip-waist relation (WHC)) assessment. Habitual food intake was
      assessed before and at the end of each session. Subjects were instructed to
      maintain the same level of physical activity during the study. RESULTS: There was
      a significant reduction on WC and WHC after the low GI session. The other
      parameters did not differ between the treatments applied in this study.
      CONCLUSION: These results suggest that the consumption of low GI foods may favor
      the prevention and control abdominal obesity and the associated metabolic
      diseases.

PMID- 23165561
TI  - [Relation of the rs9939609 gene variant in FTO with cardiovascular risk factor
      and serum adipokine levels in morbid obese patients].
AB  - BACKGROUND: Common polymorphisms of the fat mass and obesity associated gene
      (FTO) have been linked to obesity in some populations. The aim of our study was
      to analyze the relationship of the rs9939609 FTO gene polymorphism on body
      weight, cardiovascular risk factors and serum adipokine levels in morbid obese
      patients. MATERIAL AND METHODS: A sample of 129 patients with obesity was
      analyzed in a cross sectional design. Weight, blood pressure, basal glucose, c
      reactive protein (CRP), insulin, insulin resistance (HOMA), total cholesterol,
      LDL-cholesterol, HDL-cholesterol, triglycerides blood and adipocytokines (leptin,
      adiponectin, resistin, TNF alpha, and interleukin 6) levels were measured. A
      tetrapolar bioimpedance and a prospective serial assessment of nutritional intake
      with 3 days written food records were realized. Genotype of FTO gene polymorphism
      (rs9939609) was studied. RESULTS: Forty three patients (31.8%) had TT genotype,
      55 patients (42.6%) TA genotype and 33 patients (25.6%) AA genotype. Body mass
      index (43.6 (2.6) kg/m2 vs. 44.1 (2.9) kg/m2; p < 0.05), fat mass (52.0 (12.5) kg
      vs. 56.3 (11.7) kg: p < 0.05), weight (111.6 (16.2) kg vs. 114.9 (18.9) kg; p <
      0.05), levels of C reactive protein (6.1 (4.3) mg/dl vs. 9.8 (7.1) mg/dl; p <
      0.05) and levels of leptin (65.9 (52.2) ng/ml vs. 110.9 (74.1); < 0.05) were
      higher in mutant type group (A allele) than wild genotype group (TT). CONCLUSION:
      The FTO gene polymorphism, rs9939609, was found to be associated with weight, fat
      mass, C reactive protein and leptin levels in morbid obese patients with A
      allele.

PMID- 23165562
TI  - Mice fed with a high fat diet show a decrease in the expression of "toll like
      receptor (TLR)2 and TLR6 mRNAs in adipose and hepatic tissues.
AB  - INTRODUCTION: Pattern-recognition receptors (PRRs), which include Toll-like
      Receptor (TLRs) and Nacht leucine-rich repeat proteins (NLRP/NALPs), are
      molecules of innate immunity able to recognize a wide variety of ligands present
      in microorganisms and human tissues. Adipocytes (fat cells) may play an important
      role in the physiological regulation of their own immune responses via TLRs.
      During obesity, the inflammatory pathway is triggered and insulin responsiveness
      is altered in fat tissue as a result of TLR4 activation by dietary lipids.
      OBJECTIVE: Here, we investigate if other PRR family members could also
      participate in the inflammatory processes in the adipose tissue of obese mice.
      METHODS: The mRNA expression of TLRs, the NLRP3-inflammasome (NLRP3, ASC, caspase
      1 and IL-lbeta), IL-6, and TNFalpha in the hepatic and adipose tissues of mice
      fed with a high fat diet (HFD) were studied by RT-PCR. RESULTS: Adipose tissue
      from mice fed with a HFD had decreased expression levels of TLR2, TLR6 and TLR7
      and was similar to the pattern in hepatic tissue HFD mice. IL-6 and TNF-alpha
      expression also were decreased in adipose tissue of mice fed with a HFD. NLRP3
      inflammasome expression was not modified. CONCLUSION: These results suggest that
      the low expression of TLR2, and TLR6 in the mice fed with a HFD could be
      regulating the inflammation induced by the diet employed in this study.

PMID- 23165563
TI  - [Green tea and its role on chemoprevention in vivo of genotoxic damage induced by
      carcinogenic metals (chromium [VI])].
AB  - BACKGROUND: Consumption of green tea, by its antioxidant properties, has been
      associated with beneficial health effects, because antioxidant may play a role in
      the risk and pathogenesis of several chronic diseases, especially cardiovascular
      disease and cancer. On the other hand, it has been reported that metal compounds
      such as chromium [VI] are carcinogenic and can induce genotoxic damage through
      the Oxidative Stress. Therefore, it is possible that green tea has a protective
      effect against the genotoxic damage induced by this compounds. OBJECTIVE: To
      evaluate the effect of oral administration of green tea over the genotoxic damage
      induced by Cr [VI] by quantification of micronucleus (MN) in polychromatic
      erythrocytes (EPC). MATERIALS AND METHODS: We use mice of CD-1 strain that were
      randomly divided into the following groups: (i) control, (ii) treatment with
      green tea, (iii) treatment with chromium trioxide, (iv) treatment with green tea
      and chromium trioxide. The green tea was administrated via intragastric tube
      every 12 hours over two days (4 doses of 0.25 ml infusions 1.6 g/7.5 ml) and ad
      libitum (5.6 ml/day for 10 days infusions of 3.2 g/100 ml), while chromium
      trioxide was administrated via intraperitoneal (20 mg/kg). Blood samples were
      obtained from the caudal vein, the number of MN in EPC was assessed at 0, 24, 48
      and 72 hours after the treatments. RESULTS: The group treated with green tea
      showed no significant statistical changes in the average of MN. On the other
      hand, the group that was dosed with the chromium trioxide showed an increase
      between 4 and 8 MN, which was statistically significant when compared with
      control group, which confirmed the genotoxic damage. When the green tea treatment
      was administered before the application of chromium trioxide, there was a
      decrease in MN frequencies of 31 and 62% at 72 hours, 20 and 35% at 48 hours and
      18 and 31% at 24 hours with intragastric and ad libitum respectively, compared
      with the group treated only with chromium trioxide. Hence, green tea reduced the
      genotoxic damage induced by chromium trioxide, and the highest protection was
      presented at 72 hours. CONCLUSIONS: Our findings support the protective effects
      of green tea against the damage of genetic material, induced by metal compounds
      such as chromium [VI], suggesting that its antioxidant compounds are those that
      have a chemopreventive effect on the EOX generated by the Cr [VI] during its
      reduction to Cr (III). The fact that the largest decrease in the frequency of MN
      was observed at 72 hours and ad libitum treatment, suggests that, the protective
      effect depends on the bioavailability, pharmacodynamics and pharmacokinetics of
      the active ingredient in green tea, so the administration of green tea for a long
      period of time before the exposure to Cr [VI] could have a more consistent
      preventive effect.

PMID- 23165564
TI  - [Nutritional support response in critically ill patients; differences between
      medical and surgical patients].
AB  - OBJECTIVE: To assess the nutritional response of a group of critically ill
      patients, as well as the differences in the response to nutritional support
      between medical and surgical patients. METHODS: One-year long retrospective study
      including critically ill patients on artificial nutrition for 7 days. Throughout
      the first week, three nutritional biochemical controls were done that included
      albumin, prealbumin, transferrin, cholesterol, and electrolytes. Other data
      gathered were: nutritional risk index, age, gender, weight, height, APACHE, delay
      of onset of nutritional support, access route, predicted and real caloric intake,
      medical or surgical patient, hospital stay, duration of the central venous
      catheter, urinary tube, and/or mechanical ventilation, incidence and density of
      incidence of nosocomial infections. RESULTS: Sixty-three patients were studied,
      30 (47%) medical and 33 (53%) surgical/trauma patients, with a usage of EN higher
      among medical patients (16/30, 53% vs. 5/33, 15%), PN higher among surgical
      patients (25/33, 76%), and mixed nutrition similar in both groups (5 medical and
      3 surgical patients) (p = 0.001). There were no differences between medical and
      surgical patients regarding: both predicted and real caloric and nitrogenous
      intake, APACHE, delay of onset of nutrition, phosphorus, magnesium or glucose
      levels, mortality and incidence of nosocomial infections. There were no
      differences either in hospital stay or use of mechanical ventilation, although
      these tended to be lower in surgical patients. The baseline biochemical
      parameters did not show differences between both groups, although they were worse
      among surgical patients. These patients presented during the study period steady
      albumin levels with improvement in the remaining parameters, whereas medical
      patients showed a decrease in albumin and transferrin levels, steady prealbumin
      levels, and slightly improvement in cholesterol levels. CONCLUSIONS: We have
      observed higher usage of PN among surgical patients, which showed worse baseline
      nutritional biochemical parameters and responded better to nutritional support
      and having a trend towards shorter hospital stay and lower mechanical ventilation
      use than medical patients. We have not observed differences regarding the
      mortality or nosocomial infection.

PMID- 23165565
TI  - [Impact of quality improvement process upon the state of nutritional support in a
      critical care unit].
AB  - INTRODUCTION: In a preceding article the state of Nutritional support (NS) in an
      Intensive Care Unit (ICU) was documented [Martinuzzi A et al. Estado del soporte
      nutricional en una unidad de Cuidados criticos. RNC 2011; 20: 5-17]. In this
      follow-up work we set to assess the impact of several organizational, recording
      and educational interventions upon the current state of NS processes. MATERIALS
      AND METHODS: Interventions comprised presentation of the results of the audit
      conducted at the ICU before the institution's medical as well as paramedical
      personnel; their publication in a periodical, peer-reviewed journal; drafting and
      implementation of a protocol regulating NS schemes to be carried out at the ICU;
      and conduction of continuous education activities on Nutrition (such as "experts
      talks", interactive courses, and training in the implementation of the NS
      protocol). The state of NS processes documented after the interventions was
      compared with the results annotated in the preceding article. Study observation
      window ran between March the 1st, 2011 and May 31th, 2011, both included.
      RESULTS: Study series differed only regarding overall-mortality: Phase 1: 40.0%
      vs. Phase 2: 20.5%; Difference: 19.5%; Z = 1.927; two-tailed-p = 0.054.
      Interventions resulted in a higher fulfillment rate of the prescribed NS
      indication; an increase in the number of patients receiving >= 80% of prescribed
      energy; and a reduction in the number of NS lost days. Mortality was
      (numerically) lower in patients in which the prescribed NS scheme was fulfilled,
      NS was early initiated, and whom received >= 80% of prescribed energy. Adopted
      interventions had no effect upon average energy intakes: Phase 1: 574.7 +/- 395.3
      kcal/24 h-1 vs. Phase 2: 591.1 +/- 315.3 kcal/24 h-1; two-tailed-p > 0.05.
      CONCLUSIONS: Educational, recording and organizational interventions might result
      in a better conduction of NS processes, and thus, in a lower mortality.
      Hemodynamic instability is still the most formidable obstacle for initiating and
      completing NS.

PMID- 23165566
TI  - Anthropometric indices: predictors of dyslipidemia in children and adolescents
      from north of Brazil.
AB  - INTRODUCTION: Atherosclerosis represents a disease that begins in childhood, and
      alterations in lipid concentration play a fundamental role in the development of
      this condition. OBJECTIVE: To evaluate which of the currently applied obesity
      parameters (the body index mass, the percentage of body fat, the waist
      circumference and the upper arm fat area) can predict the risk for dyslipidemia
      in Brazilian children and adolescents. METHODS: Cross-sectional study,
      standardized anthropometric data and lipid profile were collected from 874
      subjects between the ages of 6 and 19 years. Logistic regression models were used
      to evaluate the degree of association between the anthropometric measurements and
      the lipid profile, controlling for potentially confounding variables, such as age
      and gender. RESULTS: Individuals with excess body weight, elevated percentage of
      body fat, waist circumference and upper arm fat above the 90th percentile showed
      a positive correlation with alterations in the lipid profile. After adjusting for
      age and income, a body mass index above the 85th percentile and an elevated
      percentage of body fat were the variables most strongly associated with
      dyslipidemia in the youngest subjects (odds ratio (OR) = 2.00, p < 0.001 and OR =
      1.47, p = 0.014, respectively). Children (64.5%) and adolescents aged 10-12 years
      (51.0%) had the highest rates of dyslipidemia. CONCLUSION: Compared with other
      variables, such as the percentage of body fat, the body mass index was the best
      predictor of dyslipidemia in children and adolescents.

PMID- 23165567
TI  - [Body composition related with health in veteran athletes].
AB  - OBJECTIVE: To analyze the corporal composition of veteran athletes of resistance
      and his relation with the health and quality of life. METHODOLOGY: It is a
      question of a descriptive and transverse study with a sample of 91 males (44.1 +/
      6.9 years) and 16 women (41.4 +/- 5.5 years) healthy medical instructors of
      career of resistance. For the analysis of the corporal composition there has been
      used an eight-electrode impedance meter (Inbody 720). The health and quality of
      life was analyzed by means of the scale SF-36, Spanish version. There were
      registered the values of athletic practice as for number of weekly meetings and
      duration of the session. RESULTS: The IMC, the abdominal fat and the percentage
      of fat place in healthy values, for below even of the normative values.
      Significant differences do not exist in any parameter of the corporal composition
      in relation with the number of weekly meetings of athletic practice. A negative
      correlation exists between the percentage of fat and the social function of the
      scale SF-36. The health and quality of life perceived of the veteran athletes
      presents superior values to the Spanish modals normative. CONCLUSION: The
      practice of four weekly meetings of 60 minutes of career of resistance allows to
      keep healthy parameters of composition corporal in spite of the age.

PMID- 23165568
TI  - [Comparative study of total energy expenditure estimated by Sense Wear Armband
      and Harris-Benedict equation in healthy ambulatory population; utility in clincal
      practice].
AB  - INTRODUCTION: Different methodologies for estimating total energy expenditure
      (TEE) are currently used. OBJECTIVE: To know which tool is most useful to
      estimate TEE in healthy subjects: SenseWearArmband (SWA) or Harris-Benedict (HB).
      METHODOLOGY: Cross-sectional study in 32 volunteers. SWA was placed for 24 hours
      and TEE was estimated with HB and the activity factor calculated with a 24-h
      activity questionnaire. RESULTS: The difference between both estimates of TEE was
      351.9 (95% CI 222.2 to 481.6) kcal/day (p < 0.001). This difference was
      associated with obesity, but not with sex. The value of ICC was 65.0% (95% CI
      7.8% to 86.2%) being statistically significant (p < 0.001). There was a
      significant difference in the estimation of the activity between both techniques
      [0.4 (CI 95% 0.1 to 0.7) hours (p = 0.007)]. CONCLUSIONS: A significant
      difference in the estimation of TEE using HB and SWA has been found.

PMID- 23165569
TI  - Association between nutritional risk based on the NRS-2002 test and hospital
      morbidity and mortality.
AB  - OBJECTIVE: To analyse the relationship between the presence of malnutrition (MN),
      as measured by the NRS-2002 nutritional evaluation, and the rate of morbidity and
      mortality. DESIGN: Cross-sectional study. SETTING: Patients admitted to Mateu
      Orfila Hospital, the regional hospital for the island of Menorca, Spain.
      SUBJECTS: 1,075 patients who were admitted to Mateu Orfila Hospital (Menorca) who
      had laboratory studies and a nutritional risk (NR) evaluation available were
      studied. Those who had a clinical suspicion of MN or those at risk were studied.
      INTERVENTION: Demographic (age, gender) and clinical (current weight, normal
      weight, body mass index, weight loss, oral intake, presence of intestinal
      failure, fistula, renal failure, respiratory infection, urinary infection,
      hyperglycaemia, admission to the ICU, hospital stay, days of parenteral nutrition
      treatment and reason for admission) were collected during hospitalisation, as
      well as hospital mortality and mortality at 6 months following discharge. All
      underwent the NRS-2002 test. RESULTS: The mean patient age was 67.9 years and
      58.3% were men. 62% of patients met the criteria for manutrition according to the
      NRS-2002 test. A statistically significant association was seen between
      malnutrition according to the NRS-2002 and intestinal failure, fistula, renal
      failure, respiratory infection, hyperglycemia, hospital mortality and mortality
      at 6 months. CONCLUSION: Malnutrition affects more than half of the patients who
      are admitted to a medium-long admission hospital and it is associated with
      increased morbidity and mortality. The results underscore the need to establish
      an update plan and preventative and therapeutic nutritional follow-up. These
      measures reduce the rate of avoidable complications and save the costs associated
      with them.

PMID- 23165570
TI  - [Risk factors for metabolic syndrome in a population with sleep apnea; evaluation
      in a population of Granada; the Granada study].
AB  - INTRODUCTION: The Metabolic Syndrome is one of the first health problems in the
      public health of the century. It's consider that the beginning of the syndrome is
      determined by numerous factors that developed two main metabolic disturbances:
      the insulin resistance and the central obesity. This relationship is
      concentrating the scientific world. As the cause-effect relationship has to be
      answered, the epidemiologic research has focused on without results. MATERIAL AND
      METHODS: 1,016 subjects were recruited in the sleep disorders laboratory in San
      Cecilio Hospital with sleep apnea suspicion. RESULTS: Significant correlation (p
      < 0,001) was found between sleep apnea severity and nocturnal saturation values
      and the different metabolic disturbances related to the metabolic syndrome
      (Hypertension, Diabetes and obesity). By the contrary, we doesn't found
      significant differences between No-Sleep apnea group and moderate sleep apnea
      group in the majority of the variables. CONCLUSIONS: Subjects with sleep apnea
      have significantly more possibilities to develop metabolic syndrome, and
      cardiovascular pathology. These subjects had to be evaluated in this sense to
      reduce the impact associated to this pathology.

PMID- 23165571
TI  - Hypoglycemic effect of cooked Lupinus mutabilis and its purified alkaloids in
      subjects with type-2 diabetes.
AB  - Developing countries are experiencing an epidemic of chronic non-communicable
      chronic diseases with high socio-economic costs. Studies of traditional foods
      with beneficial health properties could contribute to diminish these problems.
      Legumes rich in proteins like Lupinus mutabilis decreases blood glucose and
      improves insulin sensitivity in animals and humans. We report the results of a
      phase II clinical trial conducted to assess the role of cooked L. mutabilis and
      its purified alkaloids on blood glucose and insulin in volunteers with diabetes.
      Results indicate that consumption of cooked L. mutabilis or its purified
      alkaloids decreased blood glucose and insulin levels. The decreases in serum
      glucose concentrations from base line to 90 minutes were statistically
      significant within both treatment groups; however, there were not differences
      between groups. Serum insulin levels were also decreased in both groups however
      the differences were not statistically significant. None of the volunteers in
      either group presented side effects.

PMID- 23165572
TI  - [Metoclopramide as a risk factor for postprandial hyperglycemia in type 2
      diabetes].
AB  - Diabetes mellitus is a pathology that has widely spread througout the world in
      the past decades. Postprandial hyperglycemia plays an important role in the
      progress of the disease due to the fact that increases the risk for
      cardiovascular events. This study's aim was to determine if the use of
      intravenous metoclopramide in patients with Diabetes Mellitus increases the
      postprandial glycemia. MATERIAL AND METHODS: A cohort of patients hospitalized
      with type 2 diabetes mellitus. Patients were classified as exposed
      (metoclopramide 10 mg IV) and not exposed, and glycemia preprandial and
      postprandial at 30, 60 and 120 minutes was measured. RESULTS: There were 80
      patients in each group, and in both groups the general characteristics were
      homogeneous. The postprandial glycemia in the exposed group was higher at 30, 60,
      90 and 120 minutes, being only statistically significant at 120 minutes
      postprandial (p = < 0,001). CONCLUSIONS: In conclusion, the use of intravenous
      metoclopramide is a risk factor to develop postprandial hyperglycemia in diabetic
      patients.

PMID- 23165573
TI  - Dietary intake increases serum levels of carboxymethil-lysine (CML) in diabetic
      patients.
AB  - INTRODUCTION: Advanced glycation end products are produced endogenously, in
      association with hyperglycemia and oxidative stress. They can also be generated
      during cooking or food processing and, once absorbed, alter protein function and
      promote inflammation. METHODS: We selected 40 healthy male subjects, 17 patients
      with type 2 diabetes of both sexes and 15 patients with type 1 diabetes of both
      sexes. Each participant underwent both a food frequency questionnaire (FFQ) and
      24-hour dietary recall specially adapted for measuring CML intake, anthropometry,
      measurement of blood pressure and biochemical parameters in blood and urine.
      RESULTS: Serum CML levels were significantly higher in patients with diabetes
      compared to healthy subjects (p 0.04), showing a direct relationship between
      dietary intake and serum levels of CML in T2D patients (r 0.53 p 0.03). sCML
      levels correlated positively with length of diabetes mellitus, and inversely with
      body mass index (BMI). The most important dietary factor contributing to raise
      CML levels in these patients with diabetes was the consumption of milk powder.
      CONCLUSION: Serum levels of CML were found to be higher among diabetic subjects,
      associated to length of diabetes as expected, but also with the ingestion of
      foods containing higher amounts of ML. The consumption of milk powder in this
      group is a major determinant of increased serum levels.

PMID- 23165574
TI  - Liver function test alterations associated with parenteral nutrition in
      hospitalized adult patients: incidence and risk factors.
AB  - BACKGROUND: Parenteral nutrition-associated liver dysfunction can be progressive
      and irreversible, particularly in children and patients with long-term treatment.
      This study has assessed the incidence of abnormal liver function tests in
      hospitalized adults during short term parenteral nutrition (PN) and has
      investigated risk factors for developing alterations of each parameter. METHODS:
      A prospective cohort study of parenteral nutrition treated patients with
      preserved liver function at baseline. Variables examined included nutritional and
      clinical data and laboratory parameters. Determinations were performed before
      starting PN and weekly until liver function test alteration was observed. Risk
      factors were investigated by four stepwise forward logistical regressions.
      RESULTS: Eighty patients were included, 57.5% had liver function test
      alterations. PN mean duration was 15.9 (8-54) days. Mean days with PN and
      additional enteral/ oral nutrition were 1.5 (0-20). The following associations
      were found: gamma-glutamyl-transferase increased with soybean lipid intake and
      absolute diet; alkaline phosphatase increased with septic shock; alanine
      transaminase increased with septic shock, hyperglycemia and elevated creatinine;
      total bilirubin increased with septic shock, absolute diet, low prealbumin and
      glucose, and high creatinine. CONCLUSIONS: The incidence of altered liver
      function tests is high in adult hospitalized patients treated with short-term PN.
      However, the effect of nutritional factors in this alteration is low.
      Oral/enteral nutrition and reduction of soybean lipid supply can reduce increases
      in some liver function tests such as gamma-glutamyl-transferase and total
      bilirubin. The high association between all liver function tests and clinical
      systemic-hypermetabolic variables suggest the importance of specific nutritional
      strategies for this condition.

PMID- 23165575
TI  - Nutritional supplementation assessment with whey proteins and TGF-beta in
      patients with Crohn's disease.
AB  - Crohn's disease (CD) is a chronic inflammatory disorder that primarily affects
      the intestines, resulting in breakage of the intestinal barrier, pathological
      inflammation and nutritional disorders that encompass from trace elements
      deficiency to severe malnutrition. Nutritional interventions either alone or
      associated to drug therapy may be effective to achieve and maintain inflammation
      remission. OBJECTIVE: To evaluate usual food intake as quantitative and
      qualitatively, in CD patients; and describe the effect of a supplement containing
      whey proteins and TGF- on their body composition. PATIENTS AND METHODS: Dietary
      intake was assessed considering 42 consecutive patients, followed in a tertiary
      center, and by using the 3-day food recall and food intake frequency
      questionnaire. Body composition was assessed previously and 8 weeks after
      supplementation with a diet containing whey proteins and TGF-beta (N = 22).
      RESULTS AND DISCUSSION: Considering carbohydrates and lipids, most patients had
      adequate dietary intake according recommendations. Protein, saturated fat, B12
      vitamin and zinc intakes were higher than the recommended values. The dietary
      fiber, A, D, C and E vitamins, calcium, iron, folate, potassium and sodium
      intakes did not reach the recommended requirements in most patients. Patients
      supplemented with the whey protein and TGF-beta dietary presented a positive
      increment in their lean body mass, when compared to non-supplemented group.
      CONCLUSION: CD patients require nutritional orientation. Whey protein intake
      resulted in significant differences, such as improvement in Lean Body Mass and
      reduction in Fat percentage.

PMID- 23165576
TI  - [Quality of life and diagnosis process in adult celiacs from the Valencian
      Community].
AB  - INTRODUCTION: In adult patients, the diagnostic process for celiac disease (CD)
      is often very late and generates health complications that would be avoided by
      earlier diagnosis. The diseases of wich these patients were diagnosed before
      setting the diagnosis of CD were many and diverse. In addition, following a
      gluten-free diet (GFD) leads to a reduction in the quality of life for patients,
      who find it difficult to travel, to find accredited restaurants with menus
      without gluten, to interpretate food labels or to go to friends' houses.
      OBJECTIVE: To determine the delay in diagnosis, the satisfaction of the
      information provided by different sources and circumstances related to the
      quality of life. METHOD: A retrospective cross-sectional observational study in
      98 adult celiac through a validated questionnaire for celiac patientes. RESULTS:
      The average delay in diagnosis was 11 years and the average of doctors consulted
      prior to confirmation of the CD was 6. Osteoporosis or osteopenia were nearly
      twice as common among those who took more than five years to be diagnosed. Some
      90% say they transgress the dietary pattern, however, 58% show clinical symptoms
      due to unnoticed consumption of gluten. The impact of GFD on the quality of life
      is very high. CONCLUSIONS: Long delays in diagnosis suggest the need for greater
      awareness among physicians about the EC and the use of serological tests in
      potential patients or risk groups.

PMID- 23165577
TI  - [Viscosity changes in thickened water due to the addition of highly prescribed
      drugs in geriatrics].
AB  - INTRODUCTION: Dysphagia is a swallowing disorder with a high incidence in the
      geriatric patient related with an increased risk for undernutrition and pneumonia
      due to bronchial aspiration. In this condition, it is usual to add commercial
      thickeners in liquids, as well as the addition of drugs in this mixture to
      improve their administration. However, there are no studies regarding the
      possible change in viscosity produced by their addition. OBJECTIVES: To assess
      the change in viscosity of water thickened with commercial products by adding the
      drugs frequently used in elderly patients. METHODS: Samples of water mixed with
      the commercial thickener Resource (modified corn starch) or Nutilis (modified
      corn starch, maltodextrin, and gums: tara, xhantan, and guar) to achieve an
      intermediate consistence as "honey". The viscosity of these samples was measured
      as well as for similar samples to which one of the following drugs was added:
      galantamine, rivastigmin, ciprofloxacin, cholecalciferol, memantine, fosfomycin,
      calcium, and amoxicillin/clavulanic acid. RESULTS: In the samples with Resource
      thickener we observed decreased viscosity by adding galantamine, memantine,
      fosfomycin or calcium, and increased viscosity with amoxicillin/clavulanic acid.
      The viscosity of the samples with Nutilis(r) decreased with galantamine,
      rivastigmine, amoxicillin/clavulanic acid, fosfomycin and calcium. CONCLUSION:
      The viscosity of water with commercial thickeners may be affected by some drugs
      or their preservatives, which may influence the swallowing capability. It is
      recommended to perform further in vitro and in vivo studies in order to adjust
      these formulations if necessary.

PMID- 23165578
TI  - [Comparison of two types of surgical gastrostomies, open and laparoscopic in home
      enteral nutrition].
AB  - AIM: Exposing the complications of surgical gastrostomies used as way of home
      enteral nutritional support (HEN) and detecting the differences between the two
      techniques used in our environment: Open Surgery vs Laparoscopic Surgery.
      MATERIAL AND METHODS: Retrospective descriptive observational study of the
      surgical gastrostomies performed between 1994 and 2009 followed up by our unit.
      Have been analyzed the complications detected in our practice during the follow
      up of patients with HEN performed via open laparotomy vs. laparoscopic tecniques,
      assessing: leaks of gastric fluid to the exterior, abdominal wall irritation,
      presence of exudate, presence of exudate with positive culture that required
      antibiotical treatment, burning or loss of substance of the periostomic zone,
      breach of balloon, decubitus ulcer caused by the tube and formation of granuloma.
      RESULTS: Between 1994 and 2009, 57 surgical gastrostomies were performed: 47
      using the conventional laparotomic (open) tecnique and 10 laparoscopies. The
      average age of the patients was 57.51 +/- 17.29 years old. The most common cause
      for the performance of surgical gastrostomy was esophageal cancer (38.6%)
      followed by neurologic alterations (26.3%) and head and neck tumors (26.3%).
      97.9% of the patients who underwent to surgical gastrostomy presented at least
      one complication, meaning that only 2.1% were free of complications; meanwhile,
      50% of the patients were laparoscopic gastrostomy was performed had none of these
      complications. The most common complications were the presence of leaks of
      gastric fluid and abdominal wall irritation that appeared on 89.4% and 83%
      respectively of the laparotomic gastrostomies versus the presence of only 30% of
      both complications in laparoscopic gastrostomies being the difference
      statistically significant (p < 0.01). CONCLUSIONS: After the introduction of the
      laparoscopic technique in the performance of surgical gastrostomies has been
      observed a decrease of the complications occured during the home enteral
      nutritional support related to surgical gastrostomies.

PMID- 23165579
TI  - Drug administration through feeding tubes; an integrated qualification program.
AB  - INTRODUCTION: The literature documents numerous inconveniences of drug
      administration through feeding tubes. Actions to improve the quality of this
      practice are of great importance. OBJECTIVE: The objective of this study is to
      describe the implementation process and results of an Integrated Program to
      improve drug administration through feeding tubes in a Brazilian general
      hospital. METHODS: This is a descriptive study of a clinic quality improvement
      program which proceeded in four steps: (1) design of a data base with technical
      characteristics of oral drugs; (2) application of an identification label on non
      crushable tablets; (3) evaluation, through focal groups, of nursing technicians'
      knowledge of drug administration through feeding tubes, and formal training; (4)
      prescription review of patients prescribed enteral nutrition and subsequent
      pharmaceutical intervention. RESULTS: A list with 131 oral drugs used within the
      hospital was compiled with recommendations for their administration through
      feeding tubes. Seven non-crushable drugs were identified with "do not crush"
      labels. Formal training regarding drug administration through feeding tubes was
      elaborated incorporating findings from the focal groups and applied to the
      nursing team. Over eight months, we analyzed 888 prescriptions written for 185
      patients and addressed 263 pharmaceutical interventions to the medical team
      (which they accepted in 100% of the cases), and 105 interventions to the nursing
      team. CONCLUSIONS: Qualification programs with multiple strategies, as the one
      described here, may directly improve drug administration through feeding tubes
      and help to solve and prevent problems related to this practice.

PMID- 23165580
TI  - Randomised, double-blind and placebo-controlled study of the effect of a
      synbiotic dairy product on orocecal transit time in healthy adult women.
AB  - OBJECTIVE: To evaluate oro-cecal intestinal transit time (ITT) before and after
      administration of a dairy product containing Bifidobacterium BB12, Lactobacillus
      casei CRL 431 and fiber in healthy women. METHODS: A prospective, randomised,
      double-blind and cross-over study with a 4-phase design (run-in: time 0 [T0], two
      intervention periods: time 1 [T1] and time 3 [T3] and a wash-out: time 2, [T2])
      was performed. Participants were asked about bowel movement and fiber
      consumption. ITT was assessed by the carmine red dye method. RESULTS: Mean age
      was 40.7 years (n = 102 healthy women; 83 completed the study). In women with
      initial ITT (IITT) >= 48 h consuming the synbiotic product, mean IITT and final
      ITT (FITT) was 86.9 +/- 38.5 h and 51.2 +/- 29.8 h (-40.9%), as compared to women
      consuming the control yoghurt (IITT, 80.8 +/- 31.7 h; FITT, 69.5 +/- 31.5 h; 
      13.8%) (p = 0.001). IITT in women with functional constipation consuming the
      control yoghurt was 57.0 +/- 30.0 h; such figure increased 2.8 h after yoghurt
      consumption (FITT, 59.8 +/- 3 0.2 h; +4.9%). Conversely, IITT in women who
      received the synbiotic yoghurt was 69.0 +/- 49.6 h, with a -27.5% decrease 19 h
      later (FITT, 50.0 +/- 27.5 h; p = 0.023). Enteric lactic flora stabilization was
      significantly higher in women who initially consumed the synbiotic product (p <
      0.1). CONCLUSION: ITT decreased significantly after consumption of the synbiotic
      product. Such beneficial effect was more evident in women with IITT >= 48 h and
      with functional constipation.

PMID- 23165581
TI  - [Validation of a questionnaire of lycopene frequency intake].
AB  - INTRODUCTION: An inverse relationship between some chronic degenerative diseases
      and plasma lycopene levels has been demonstrated. Dietary intake questionnaires
      are one of the current methods most used to ascertain dietary patterns and
      explore their association with the disease risk. The main drawback of their use
      is the need for previous validation. The purpose of this study was to validate a
      frequency questionnaire in order to assess the intake of licopene, in the
      population of the Canary Islands. METHODS: A food intake frequency questionnaire
      was designed and administered to 70 patients of the Plastic Surgery Service of
      the Hospital Universitario Insular de Gran Canaria. Estimated lycopene intake
      from the food intake frequency questionnaire was examined in relation to plasma
      lycopene levels, measured by HPLC. RESULTS: The Spearman correlation coefficient
      between estimated lycopene intake and plasma levels was 0,421 and the validity of
      the questionnaire was demonstrated. Furthermore, an association between obesity
      and some pathologies with plasma lycopene levels was observed, although not
      statistically significant. CONCLUSIONS: The food intake frequency questionnaire
      is valid and it could be useful in epidemiological studies in the population of
      the Canary Islands.

PMID- 23165582
TI  - Does treatment guided by vitamin K in the diet alter the quality of life of
      anticoagulated patients?
AB  - PURPOSE: To compare whether health-related quality of life (HRQoL) is altered in
      patients undergoing a treatment strategy guided by changes in dietary vitamin K.
      METHODS: This study is a randomized clinical trial carried out with chronic oral
      anticoagulation outpatients randomized into a control group (conventional dose
      adjustment of oral anticoagulants) (n = 66) and an intervention group (strategy
      based on changes in dietary vitamin K intake) (n = 66). HRQoL was measured using
      the Duke Anticoagulation Satisfaction Scale (DASS) at baseline and 90 days of
      follow-up. RESULTS: Patients with worse HRQoL were younger (p = 0.005) and were
      using a higher dose of baseline oral anticoagulants (p = 0.008), while those with
      better HRQoL scores had a higher level of education (p = 0.01). Both groups had
      significant improvements in HRQoL from baseline to 90 days in the global DASS
      score (p < 0.001), as well as in the negative and positive psychological impact
      (p < 0.001) domains. We did not observe differences in the variations of HRQoL
      scores in any of the DASS domains (p values > 0.05) between groups of
      interventions. Patients who achieved oral anticoagulation stability (n = 23) had
      significantly better HRQoL scores than patients who did not achieve stability (p
      = 0.003). CONCLUSION: Patients receiving the treatment strategy based on changes
      in dietary vitamin K intake did not have better HRQoL scores; however, both
      treatment approaches to manage oral anticoagulation improved HRQoL. Patients with
      greater oral anticoagulation stability had better HRQoL scores.

PMID- 23165583
TI  - [Carotenoid data base to assess dietary intake of carotenes, xanthophyls and
      vitamin A; its use in a comparative study of vitamin A nutritional status in
      young adults].
AB  - OBJECTIVES: 1) Develop a database of carotenoids (BD-carotenoids) in foods widely
      consumed in Spain. 2) To assess the vitamin A nutritional status (expressed as
      retinol equivalents [RE] and retinol activity equivalents [RAE]) in young adults.
      METHODS: The BD-carotenoids includes data on carotenes (beta-carotene, alpha
      carotene and lycopene) and xanthophylls (beta-cryptoxanthin, lutein and
      zeaxanthin) generated by HPLC. Vitamin A intake was assessed by a 3-day food
      record in 54 adults (20-35 years of age, not obese and with serum retinol > 30
      ug/dl), using the BD-carotenoids and a Food Composition Table widely used in
      Spain. RESULTS: The BD-carotenoids includes data on 89 foods (9 raw or boiled and
      14 processed). The intake of provitamin-A carotenoids is 2.5 mg/p/d, that of RE
      682 ug/p/d and that of RAE 499 ug/p/d. The vitamin A intake expressed as RAE is
      27% lower than that expressed as RE. Seventy-six percent of the intake meets the
      daily intake recommendations and 63% meets the reference daily intakes of vitamin
      A. CONCLUSIONS: Data on individual carotenoids ensure greater accuracy in studies
      on diet and health, and provide easier assessment of the vitamin A intake,
      expressed as RE, RAE, or any other future forms. The vitamin A intake expressed
      as RAE represents a substantial reduction in the carotenoid contribution to
      vitamin A intake, which enhances the detection of inadequacies of that intake.

PMID- 23165584
TI  - Risk factors associated with hepatic steatosis: a study in patients in the
      Northeast Brazil.
AB  - INTRODUCTION: Although there are several studies in the international literature
      regarding hepatic steatosis, few large-scale studies of risk factors are
      available. OBJECTIVE: To verify potential risk factors associated with hepatic
      steatosis, such as: alcohol consumption, overweight, dyslipidemia, hypertension,
      and type 2 diabetes mellitus. METHODS: This is a case series study including a
      control group (without hepatic steatosis), carried out at the gastroenterology
      outpatient clinic in Northeast Brazil. The sample was composed of 219 patients
      with hepatic steatosis and 82 without the disease. RESULTS: There was an
      association between hepatic steatosis and socioeconomic status. Prevalence Ratio
      (PR) for family income <= 2 minimum wage was (PR = 1.35 CI 95%, 1.18-1.54) and
      education level < primary education (PR = 1.44, CI 95%,1.27-1.64). Regarding
      anthropometric and clinical characteristics and lipid profile, there was an
      association with overweight (PR = 1.59, CI 95%, 1.38-1.83), abdominal
      circumference in the range of very high risk (PR = 2.28, IC 95%,1.68-3.09),
      hypertension (PR = 1.30, CI 95%, 1.15-1.48) and type 2 diabetes mellitus (PR =
      1.23, CI 95%, 1.07-1.64), low HDL-cholesterol (PR = 1,96, CI 95%, 1.55-2.48),
      hypertriglyceridemia (PR = 2.10, CI 95%, 1.64-2.68). In the regression model
      three variables remained independently associated to hepatic steatosis, abdominal
      circumference in the range of very high risk (PRadjusted = 1.74), low HDL
      cholesterol (PRadjusted = 1.39) and overweight (PRadjusted = 1.28). CONCLUSION:
      The results showed an association of hepatic steatosis with some risk factors,
      being abdominal circumference (very high risk) the most strongly associated,
      followed by low HDL-cholesterol and overweight.

PMID- 23165585
TI  - Overweight, obesity and weight gain up to three years after liver
      transplantation.
AB  - INTRODUCTION: Previous studies have shown that weight gain commonly occurs after
      liver transplantation (LTx). Few risk factors have been studied. OBJECTIVES: The
      aim of this study was to assess the weight changes and incidence excessive weight
      up to 3 years after surgery. METHODS: Post-LTx patients were assessed for their
      weight changes and incidence of excessive weight before liver disease; on the
      first outpatient appointment after LTx; 3 and 6 mo after LTx; 1; 2 and 3y after
      LTx. Demographic, socioeconomic, lifestyle and clinical variables were collected
      to assess risk factors for weight gain, overweight and obesity using linear and
      logistic regression analysis. RESULTS: Eighty patients undergoing LTx between
      1997/2006 were assessed. Patients lost an average of 9.1 kg during liver disease.
      This weight was recovered within 1 year after surgery; after 3 years, patients
      had gained an average of 11.6 kg. The incidence of excessive weight increased
      over the years, and 56.4% of patients were overweight in the 3 years after LTx;
      most of them were obese (30.0%). Risk factors for weight gain on the third year
      after LTx were greater BMI before liver disease (p < 0.01); former smoker (p <
      0.01); family history of overweight (p = 0.04); being hosewife/unemployed/retired
      (p = 0.08); alcoholic indication for LTx (p = 0.02). Risk factors for incidence
      of excessive weight on the third year after LTx were being married (RR: 13.13;
      CI: 1.33-125.0); being former smoker (RR: 4.68; CI: 1.16-18.85); greater age at
      LTx (RR: 1.1; CI: 1.02-1.20). CONCLUSIONS: Post-LTx patients experienced weight
      gain after surgery, mainly during the 1 year after operation and increased
      progressive incidence up to 3 years, due to different risk factors, some of them
      can be prevented.

PMID- 23165586
TI  - [The registry of home artificial nutrition and ambulatory of the Spanish Society
      of Parenteral and Enteral Nutrition; SWOT analysis].
AB  - OBJECTIVE: To evidence by means of a SWOT-R analysis performed by an expert
      consensus the most worrying characteristics of the register on Home-based and
      Outpatient Artificial Nutrition. MATERIAL AND METHODS: SWOT-R analysis with
      expert consensus. We requested the participation of the active members of the
      NADYA group within the last 5 years with the premise of structuring the SWOT-R
      based on the characteristics of the NADYA registry from its beginning. RESULTS:
      18 experts from hospitals all over Spain have participated. The internal analysis
      seems to be positive, presenting the registry as having important resources. The
      external analysis did not show a great number of threats, there are very potent
      factors, "the voluntariness" of the registry and the "dependence on external
      financing". The opportunities identified are important. The recommendations are
      aimed at stabilizing the system by decreasing the threats as one of the main
      focus of the strategies to develop as well as promoting the items identified as
      opportunities and strengths. CONCLUSIONS: The analysis shows that the NADYA
      register shows a big potentiality for improvement. The proposed recommendations
      should be structured in order to stay on the track of development and quality
      improvement that has characterized the NADYA register from the beginning.

PMID- 23165587
TI  - [Percutaneous gastrostomy complicated with abdominal wall hematoma; severe anemia
      secondary to percutaneous endoscopic gastrostomy].
AB  - Endoscopic percutaneous gastrostomy (PEG) is a safe and effective procedure that
      offers clear advantages over nasogastric tube feeding to ensure adequate
      nutrition in patients with swallowing problems who have an intact digestive
      tract. With proper placement and monitoring methodology there are few
      complications in both the peritrack procedure as in the long run. However,
      despite being considered a safe technique it is not devoided of serious
      complications. We report a patient with dysphagia, requiring percutaneous
      endoscopic gastrostomy placement developing a severe anemia with severe
      subcutaneous hematoma, given the exceptional case and literature review.

PMID- 23165588
TI  - [Acute gastric dilatation in a bulimic patient; systemic efects].
AB  - OBJECTIVES: To demonstrate through a clinical case the systemic effetcss and
      complications that can arise after an acute gastric dilatation caused by an
      eating binge. CLINICAL CASE: A young woman diagnosed of bulimia nervosa presents
      to the emergency room after a massive food intake. She shows important abdominal
      distention and refers inability to self-induce vomit. A few hours later she
      commences to show signs of hemodynamic instability and oliguria. A CT scan is
      performed; it shows bilateral renal infarctions due to compression of the
      abdominal aorta and some of its visceral branches. INTERVENTIONS: The evaluation
      procedures included quantification of the gastric volume by CT. A decompression
      gastrostomy was performed; it allowed the evacuation of a large amount of gastric
      content and restored blood supply to the abdomen, which improved renal perfusion.
      CONCLUSIONS: CT is a basic diagnostic tool that not only allows us to quantify
      the degree of acute gastric dilatation but can also evaluate the integrity of the
      adjacent organs which may be suffering compression hypoperfusion.

PMID- 23165589
TI  - [Evaluation of scientific publications and professional life of a scientist].

PMID- 23165590
TI  - Facile synthesis and characterization of highly fluorescent and biocompatible N
      acetyl-L-cysteine capped CdTe/CdS/ZnS core/shell/shell quantum dots in aqueous
      phase.
AB  - The synthesis of water-soluble quantum dots (QDs) in aqueous phase has received
      much attention recently. To date various kinds of QDs such as CdTe, CdSe,
      CdTe/CdS and CdSe/ZnS have been synthesized by aqueous methods. However,
      generally poor-quality QDs (photoluminescent quantum yield (PLQY) lower than 30%)
      are obtained via this method and the 3-mercaptopropionic acid stabilizer is
      notorious for its toxicity and awful odor. Here we introduce a novel thiol
      ligand, N-acetyl-L-cysteine, as an ideal stabilizer that is successfully employed
      to synthesize high-quality CdTe/CdS/ZnS QDs via a simple aqueous phase. The
      core/shell/shell structures of the CdTe/CdS/ZnS QDs were verified by x-ray
      photoelectron spectroscopy, energy dispersive x-ray spectroscopy, x-ray powder
      diffraction and transmission electron microscopy. These QDs not only possess a
      high PLQY but also have excellent photostability and favorable biocompatibility,
      which is vital for many biological applications. This type of water-dispersed QD
      is a promising candidate for fluorescent probes in biological and medical fields.

PMID- 23165591
TI  - Development of automated paper-based devices for sequential multistep sandwich
      enzyme-linked immunosorbent assays using inkjet printing.
AB  - To the best of our knowledge, this is the first report on paper-based devices for
      automating the sequential multistep procedures of a sandwich-type enzyme-linked
      immunosorbent assay (ELISA) that require only a single-step application of the
      sample solution. The device was based on a piece of nitrocellulose (NC) membrane
      with specially designed channels, where all the reagents are applied at different
      locations in order to control the fluid travel to the detection region. The
      inkjet printing method, a simple and low-cost process, was used to create the
      flow channel and device barrier patterns. The fabricated barrier was found to be
      an efficient boundary for the liquid along the printed design in the NC membrane,
      enabling direct control of the reagent flow time. ELISA results were obtained
      with a single-step sample application. The developed devices (so-called automated
      paper-based devices) provided a simple procedure for the sandwich ELISA, while
      reducing assay time and reagent consumption. Colorimetric results were measured
      using digital camera imaging with software processing. The capability of the
      method developed herein was successfully used to determine the levels of human
      chorionic gonadotropin (hCG) by ELISA.

PMID- 23165592
TI  - Structural transformation of Sb-based high-speed phase-change material.
AB  - The crystal structure of a phase-change recording material (the compound
      Ag(3.4)In(3.7)Sb(76.4)Te(16.5)) enclosed in a vacuum capillary tube was
      investigated at various temperatures in a heating process using a large Debye
      Scherrer camera installed in BL02B2 at SPring-8. The amorphous phase of this
      material turns into a crystalline phase at around 416 K; this crystalline phase
      has an A7-type structure with atoms of Ag, In, Sb or Te randomly occupying the 6c
      site in the space group. This structure was maintained up to around 545 K as a
      single phase, although thermal expansion of the crystal lattice was observed.
      However, above this temperature, phase separation into AgInTe(2) and Sb-Te
      transpired. The first fragment, AgInTe(2), reliably maintained its crystal
      structure up to the melting temperature. On the other hand, the atomic
      configuration of the Sb-Te gradually varied with increasing temperature. This
      gradual structural transformation can be described as a continuous growth of the
      modulation period gamma.

PMID- 23165593
TI  - On the structural relations of malachite. II. The brochantite MDO polytypes.
AB  - The structural relation between malachite and the brochantite MDO (maximum degree
      of order) polytypes is discussed. It is demonstrated that the same building
      blocks which form the basis of brochantite polytypism also occur in malachite.
      The different arrangements of these building blocks in the two mineral structures
      are rationalized as a result of the different coordination geometries required by
      the respective non-metal atoms acting as linkers. The compound stoichiometries
      are discussed in light of a common structured formula scheme, in which pairs of H
      atoms can play a similar role as single non-H atoms. An overview on the
      occurrence of malachite-like building blocks in several other crystal structures
      is given.

PMID- 23165594
TI  - Comparative structural study of decagonal quasicrystals in the systems Al-Cu-Me
      (Me = Co, Rh, Ir).
AB  - A comparative single-crystal X-ray diffraction structure analysis of the family
      of Al-Cu-Me (Me = Co, Rh and Ir) decagonal quasicrystals is presented. In
      contrast to decagonal Al-Cu-Co, the other two decagonal phases do not show any
      structured disorder diffuse scattering indicating a higher degree of order.
      Furthermore, the atomic sites of Rh and Ir can be clearly identified, while Cu
      and Co cannot be distinguished because of their too similar atomic scattering
      factors. The structure models, derived from charge-flipping/low-density
      elimination results, were refined within the tiling-decoration method but also
      discussed in the five-dimensional embedding approach. The basic structural
      building units of the closely related structures are decagonal clusters with 33 A
      diameter, which are consistent with the available electron-microscopic images.
      The refined structure models agree very well with the experimental data.

PMID- 23165595
TI  - Mode-crystallography analysis and magnetic structures of SrLnFeRuO6 (Ln = La, Pr,
      Nd) disordered perovskites.
AB  - The crystal and magnetic structures of SrLnFeRuO(6) (Ln = La, Pr, Nd) double
      perovskites have been investigated. All compounds crystallize with an
      orthorhombic Pbnm structure at room temperature. These materials show complete
      chemical disorder of Fe and Ru cations for all compounds. The distortion of the
      structure, relative to the ideal cubic perovskite, has been decomposed into
      distortion modes. It has been found that the primary modes of the distortion are
      octahedral tilting modes: R(4)(+) and M(3)(+). The crystal structure of
      SrPrFeRuO(6) has been studied from room temperature up to 1200 K by neutron
      powder diffraction. There is a structural phase transition from orthorhombic
      (space group Pbnm) to trigonal (space group R3c) at T = 1075 K. According to
      group theory no second-order transition is possible between these symmetries.
      Magnetic ordering for all the compounds is described by the magnetic propagation
      vector (0,0,0). SrPrFeRuO(6) shows ferrimagnetic order below ca 475 K, while
      SrLaFeRuO(6) (below ca 450 K) and SrNdFeRuO(6) (below ca 430 K) exhibit canted
      antiferromagnetic order. The magnetic moments at low temperatures are m(Fe/Ru) =
      1.88 (3)MU(B) for SrLaFeRuO(6) (2 K), m(Pr) = 0.46 (4)MU(B) and m(Fe/Ru) =
      2.24MU(B) for SrPrFeRuO(6) (2 K), and m(Fe/Ru) = 1.92MU(B) for SrNdFeRuO(6) (10
      K).

PMID- 23165596
TI  - Dinuclear oxofluorometallates as a new structural type of d(0) transition metal
      oxofluoride compound.
AB  - Five isomorphous d(0) transition metal oxofluoride compounds A(3)[M(2)O(x)F(11
      x)].(AF)(0.333) (A = K, Rb, NH(4); M = Nb, Mo, W; x = 2, 4) have been synthesized
      from acid fluoride solutions, and their crystal structures have been determined
      by single-crystal X-ray diffraction. The basic structural building units are
      dinuclear M(2)X(11) (dimers) formed from NbOF(5) or Mo(W)O(2)F(4) octahedra
      connected by the fluorine bridging atom. In the Nb(2)O(2)F(9) dimer, the O atoms
      occupy apical corners. In the M(2)O(4)F(7) (M = Mo, W) dimers two O atoms are
      also apically placed, whereas the other two O atoms are statistically disordered
      in equatorial planes. The arrangement of dimers is so that the hexagonal tunnels
      containing 'free' fluoride ions are formed. During the irradiation process the
      orthorhombic structure of K(3)Nb(2)O(2)F(9).(KF)(0.333) transforms into a pseudo
      trigonal one with a = 23.15 A, which is the [101] diagonal of the orthorhombic
      unit cell. The other four trigonal crystals are merohedral twins.

PMID- 23165597
TI  - Structures from MnX2 and proline: isomorphous racemic compounds and a series of
      chiral non-isomorphous chain polymers.
AB  - Reactions of manganese(II) chloride, bromide and iodide with proline as an
      enantiopure and racemic ligand result in six crystalline solids for which
      diffraction experiments have been performed at 100 K. For two of these compounds,
      crystal structures at ambient temperature had been reported previously. The most
      surprising outcome of our systematic comparison lies in the role of chirality:
      with enantiopure proline three different coordination polymers have been
      obtained, whereas racemic proline yields isomorphous mononuclear complexes under
      the same reaction conditions.

PMID- 23165598
TI  - Hydrothermal synthesis and crystal structure of novel bis(6-carboxypyridine-2
      carboxylato-kappa3O2,N,O6)nickel(II) trihydrate, Ni(Hpydc)2.3H2O.
AB  - The synthesis and crystal structure of the compound bis(6-carboxypyridine-2
      carboxylato-kappa(3)O(2),N,O(6))nickel(II) trihydrate, Ni(Hpydc)(2).3H(2)O, with
      a supramolecular network is reported (H(2)pydc is pyridine-2,6-dicarboxylic
      acid). The compound has been prepared by hydrothermal methods. The crystal
      structure has been solved by direct methods using single-crystal X-ray
      diffraction data collected at 293 K and refined by full-matrix least-squares
      procedures to a final R value of 0.0323 for 2779 observed reflections. The
      compound has distorted octahedral geometry around the metal centre. The complex
      contains two identical singly ionized ligand molecules. The nickel(II) is bonded
      to four O atoms and two N atoms from the tridentate ligand molecules, which are
      nearly perpendicular to each other. Hydrogen-bonded interactions create a three
      dimensional supramolecular porous network. The supramolecular structure accounts
      for the porous structure of the compound as is evident from the Brunauer, Emmett
      & Teller (BET) surface area of 80 m(2) g(-1). Thermal degradation of the compound
      shows that lattice water molecules give stability to the crystal structure.

PMID- 23165599
TI  - Charge-density distribution in potassium dihydrogen phosphoglycolate--a
      comparison of phosphate and phosphonate groups.
AB  - Analysis of the experimental and theoretical charge-density distribution in
      potassium dihydrogen phosphoglycolate has been performed. The P-O bonds in the
      phosphate group are more polarized and the P atom is more positively charged than
      in phosphonate groups. The P-O bonds belong to a transit closed-shell (or polar
      covalent) class, while the ester C-O bond is a covalent (or shared-shell) bond.
      The coordination of potassium exerts a small effect on the phosphate group,
      whereas more pronounced changes, e.g. concerning the ellipticities of the C-O
      bonds, may be observed. The profiles of Laplacians and ellipticities give more
      insight in the polarization of the bonds.

PMID- 23165600
TI  - The first report of the crystal structure of non-solvated MU-oxo boron
      subphthalocyanine and the crystal structures of two solvated forms.
AB  - The first instance of the solvent-free X-ray determined single-crystal structure
      of the oxygen-bridged boron subphthalocyanine dimer [MU-oxo-(BsubPc)(2),
      C(48)H(24)B(2)N(12)O] is reported. Single crystals obtained by train sublimation
      were found to have MU-oxo-(BsubPc)(2) organized into a C2/c space group. The
      crystal structure obtained by sublimation is of particular interest as it is
      highly symmetric and also of notably high density when compared with other BsubPc
      crystals. The acquisition of this crystal structure came about from the direct
      chemical synthesis of MU-oxo-(BsubPc)(2) followed by a work-up which culminated
      in obtaining the single crystals by sublimation. Several methods for the direct
      chemical synthesis of MU-oxo-(BsubPc)(2) were also investigated each using
      dichlorobenzene as the solvent. On standing, these reaction mixtures produced a
      crystal of the dichlorobenzene (DCB) solvate of MU-oxo-(BsubPc)(2) [MU-oxo
      (BsubPc)(2).2DCB]. It is also reported that the conversion of bromo-boron
      subphthalocyanine (Br-BsubPc) to MU-oxo-(BsubPc)(2) happens on train sublimation
      which resulted in the acquisition of a partially hydrated crystal [MU-oxo
      (BsubPc)(2).0.25H(2)O].

PMID- 23165601
TI  - Experimental and database-transferred electron-density analysis and evaluation of
      electrostatic forces in coumarin-102 dye.
AB  - The electron-density distribution of a new crystal form of coumarin-102, a laser
      dye, has been investigated using the Hansen-Coppens multipolar atom model. The
      charge density was refined versus high-resolution X-ray diffraction data
      collected at 100 K and was also constructed by transferring the charge density
      from the Experimental Library of Multipolar Atom Model (ELMAM2). The topology of
      the refined charge density has been analysed within the Bader 'Atoms In
      Molecules' theory framework. Deformation electron-density peak heights and
      topological features indicate that the chromen-2-one ring system has a
      delocalized pi-electron cloud in resonance with the N (amino) atom. The molecular
      electrostatic potential was estimated from both experimental and transferred
      multipolar models; it reveals an asymmetric character of the charge distribution
      across the molecule. This polarization effect is due to a substantial charge
      delocalization within the molecule. The molecular dipole moments derived from the
      experimental and transferred multipolar models are also compared with the liquid
      and gas-phase dipole moments. The substantial molecular dipole moment
      enhancements observed in the crystal environment originate from the crystal field
      and from intermolecular charge transfer induced and controlled by C-H...O and C
      H...N intermolecular hydrogen bonds. The atomic forces were integrated over the
      atomic basins and compared for the two electron-density models.

PMID- 23165602
TI  - Structures of four polymorphs of the pesticide dithianon solved from X-ray powder
      diffraction data.
AB  - The crystal structures of four polymorphs of the pesticide dithianon (5,10
      dihydro-5,10-dioxonaphtho[2,3-b]-1,4-dithiine-2,3-dicarbonitrile) have been
      solved from powder diffraction data and refined using the Rietveld method. Three
      polymorphs crystallize in non-centrosymmetric space groups. Two polymorphs have
      Z' > 1. The structures are assembled via interactions between carbonyl groups of
      quinoid fragments into layers which further interact only by weak interactions.

PMID- 23165603
TI  - Solvatomorphism of 9,9'-[1,3,4-thiadiazole-2,5-diylbis(2,3-thiophendiyl-4,1
      phenylene)]bis[9H-carbazole]: isostructurality, modularity and order-disorder
      theory.
AB  - During a systematic investigation of the crystallization behaviour of 9,9'-[1,3,4
      thiadiazole-2,5-diylbis(2,3-thiophendiyl-4,1-phenylene)]bis[9H-carbazole] (I),
      six single crystalline solvates were obtained and characterized by X-ray
      diffraction at 100 K. The structure of the hemi-2-butanone (MEK) solvate contains
      two crystallographically independent molecules of (I) related by pseudo-inversion
      symmetry. The structure is polytypic and composed of non-polar (I) layers and
      polar solvent layers. It can be described according to an extended order-disorder
      (OD) theory with relaxed vicinity condition. The observed polytype is of a
      maximum degree of order (MDO). Layer triples of the second MDO polytype are shown
      by twinning by inversion. The mono-benzene and mono-toluene solvates are
      isostructural. Whereas the (I) layers are isostructural to those of the idealized
      description of the hemi-MEK solvate, the solvent layers are non-polar, resulting
      in a fully ordered structure. The toluene molecule is ordered, the benzene
      molecule features disorder. The (I) layers in the sesqui-dioxane and sesqui
      benzene solvates are isostructural and unrelated to those in the hemi-MEK, mono
      benzene and mono-toluene solvates. The solvent layers are isopointal in both
      sesqui-solvates, but the stacking differs significantly. The hemi
      dideuterodichloromethane (DCM-d(2)) solvate is made up of two kinds of (I) rods,
      spaced by DCM-d(2) molecules. Rods of one kind are similar to analogous rods in
      the sesqui-dioxane and the sesqui-benzene solvates, whereas rods of the other
      kind are only remotely related to rods in the hemi-MEK solvate.

PMID- 23165604
TI  - The polymorphs of ROY: application of a systematic crystal structure prediction
      technique.
AB  - We investigate the ability of current ab initio crystal structure prediction
      techniques to identify the polymorphs of 5-methyl-2-[(2-nitrophenyl)amino]-3
      thiophenecarbonitrile, also known as ROY because of the red, orange and yellow
      colours of its polymorphs. We use a methodology combining the generation of a
      large number of structures based on a computationally inexpensive model using the
      CrystalPredictor global search algorithm, and the further minimization of the
      most promising of these structures using the CrystalOptimizer local minimization
      algorithm which employs an accurate, yet efficiently constructed, model based on
      isolated-molecule quantum-mechanical calculations. We demonstrate that this
      approach successfully predicts the seven experimentally resolved structures of
      ROY as lattice-energy minima, with five of these structures being within the 12
      lowest energy structures predicted. Some of the other low-energy structures
      identified are likely candidates for the still unresolved polymorphs of this
      molecule. The relative stability of the predicted structures only partially
      matches that of the experimentally resolved polymorphs. The worst case is that of
      polymorph ON, whose relative energy with respect to Y is overestimated by 6.65 kJ
      mol(-1). This highlights the need for further developments in the accuracy of the
      energy calculations.

PMID- 23165605
TI  - Evidence from regression-discontinuity analyses for beneficial effects of a
      criterion-based increase in alcohol treatment.
AB  - Brief interventions effectively reduce alcohol problems; however, it is
      controversial whether longer interventions result in greater improvement. This
      study aims to determine whether an increase in treatment for people with more
      severe problems resulted in better outcome. We employed regression-discontinuity
      analyses to determine if drinking driver clients (n = 22,277) in Ontario
      benefited when they were assigned to a longer treatment program (8-hour versus 16
      hour) based on assessed addiction severity criteria. Assignment to the longer16
      hour program was based on two addiction severity measures derived from the
      Research Institute on Addictions Self-inventory (RIASI) (meeting criteria for
      assignment based on either the total RIASI score or the score on the recidivism
      subscale). The main outcome measure was self-reported number of days of alcohol
      use during the 90 days preceding the six month follow-up interview. We found
      significant reductions of one or two self-reported drinking days at the point of
      assignment, depending on the severity criterion used. These data suggest that
      more intensive treatment for alcohol problems may improve results for individuals
      with more severe problems.

PMID- 23165606
TI  - Mesenchymal stromal cells: radio-resistant members of the bone marrow.
AB  - Mesenchymal stromal cells (MSCs) are multi-potent adult stem cells located in
      various tissues, including the bone marrow. MSCs are key components of the
      haematopoietic stem cell (HSC) niche within the bone marrow where they function
      to maintain haematopoietic homoeostasis by regulating HSC self-renewal and
      function. Bone marrow exposure to ionising radiation causes rapid depletion of
      radio-sensitive HSCs and their progenitors, leading to haematopoietic failure.
      However, host-/patient-derived MSCs can survive radiation doses lethal to the
      haematopoietic system. The mechanisms underlying MSC radio-resistance are
      currently under intense investigation. Here, we review the current knowledge of
      MSC radio-biology. The DNA damage response (DDR) represents an orchestrated
      network of signalling pathways that enable cells to respond to genotoxic damage.
      We discuss in detail the emerging importance of the DDR in mediating MSC radio
      resistance and examine the DDR of MSCs in the context of other stem cell types.
      Finally, we examine future advances in understanding MSC radio-resistance and
      discuss the potential impact of the radio-resistance of these stem cells for the
      clinic.

PMID- 23165607
TI  - P38 and JNK have opposing effects on persistence of in vivo leukocyte migration
      in zebrafish.
AB  - The recruitment and migration of macrophages and neutrophils is an important
      process during the early stages of the innate immune system in response to acute
      injury. Transgenic pu.1:EGFP zebrafish permit the acquisition of leukocyte
      migration trajectories during inflammation. Currently, these high-quality live
      imaging data are mainly analysed using general statistics, for example, cell
      velocity. Here, we present a spatio-temporal analysis of the cell dynamics using
      transition matrices, which provide information of the type of cell migration. We
      find evidence that leukocytes exhibit types of migratory behaviour, which differ
      from previously described random walk processes. Dimethyl sulfoxide treatment
      decreased the level of persistence at early time points after wounding and
      ablated temporal dependencies observed in untreated embryos. We then use
      pharmacological inhibition of p38 and c-Jun N-terminal kinase mitogen-activated
      protein kinases to determine their effects on in vivo leukocyte migration
      patterns and discuss how they modify the characteristics of the cell migration
      process. In particular, we find that their respective inhibition leads to
      decreased and increased levels of persistent motion in leukocytes following
      wounding. This example shows the high level of information content, which can be
      gained from live-imaging data if appropriate statistical tools are used.

PMID- 23165608
TI  - [Memorandum prevention research - research areas and methods].
AB  - From 2004 to 2012, the German Ministry of Education and Research (BMBF)
      established its first funding programme for the promotion of prevention research.
      60 projects on primary prevention and health promotion and the meta-project
      entitled "Cooperation for Sustainable Prevention Research" (KNP) received BMBF
      grants under this programme during this period. The experience and knowledge
      gained and recommendations arising from the research funded under this programme
      are compiled in memorandum format. The "Memorandum on Prevention Research -
      Research Areas and Methods" highlights 5 research areas that are considered to be
      especially relevant from the perspective of the involved scientists and practice
      partners.The promotion of structural development and sustainability enhancement
      in disease prevention and health promotion are central areas that should branch
      out from existing nuclei of crystallization. Improving the health competence of
      the population and of specific subpopulations is another major area. Research in
      these areas should contribute to the development of theoretical concepts and to
      the empirical testing of these concepts. The transfer of knowledge for effective
      use of developed disease prevention and health promotion programmes and measures
      is still a scarcely researched area. Among other things, studies of the transfer
      of programmes from one context to another, analyses of the coop-eration between
      politics and science, and the continued theoretical and conceptual development of
      transfer research are needed. Long-term data on the effects of intervention
      studies are also needed for proper evaluation of sustainability. The latter dem
      onstrates the importance of method development in disease prevention and health
      promotion research as an area that should receive separate funding and support.
      This research should include, in particular, studies of the efficacy of complex
      interventions, health economic analyses, and participative health research.

PMID- 23165609
TI  - Effect of exercise training combined with isoflavone supplementation on bone and
      lipids in postmenopausal women: a randomized clinical trial.
AB  - We determined the effects of 2 years of exercise training and soy isoflavone
      supplementation on bone mass and lipids in postmenopausal women provided with
      calcium and vitamin D. Women were randomized to four groups: exercise training
      (Ex); isoflavone supplementation (Iso: 165 mg/d [105 mg/d aglycone equivalent]);
      combined Ex and Iso (ExIso); and placebo (control). Exercise included resistance
      training (2 days/week) and walking (4 days/week). Our primary outcomes were
      lumbar spine and hip bone mineral density (BMD). Secondary outcomes included hip
      geometry, tibia and radius speed of sound (SOS), dynamic balance (6 m backward
      tandem walking), blood lipids, mammography, and endometrial thickness. A total of
      351 women (Ex = 86, Iso = 90, ExIso = 87, control = 88) were randomized, with 298
      analyzed at 2 years (Ex = 77, Iso = 76, ExIso = 72, control = 73). There was a
      significant interaction for total hip BMD (p < 0.001) such that ExIso had a
      greater rate of decrease (absolute change [95% confidence interval] = -0.018 [
      0.024, -0.012] g/cm(2) ) than either the Ex or Iso groups alone (-0.005 [-0.01,
      0.001] and -0.005 [-0.011, 0.001] g/cm(2) , respectively). There were no
      differences between groups for changes in lumbar spine BMD and minimal
      significant changes in hip geometric properties and bone SOS. Exercise groups
      improved dynamic balance as measured by a decrease in backward tandem walking
      time over 6 m (p = 0.017). Isoflavone groups decreased low density lipoproteins
      (Iso: -0.20 [-0.37, -0.02] mmol/L; ExIso: -0.23 [-0.40, -0.06] mmol/L; p = 0.003)
      compared to non-isoflavone groups (Ex: 0.01 [-0.16, 0.18] mmol/L; control: -0.09
      [-0.27, 0.08] mmol/L) and had lower adverse reports of menopausal symptoms (14%
      versus 33%; p = 0.01) compared to non-isoflavone groups. Isoflavone
      supplementation did not increase endometrial thickness or abnormal mammograms. We
      conclude exercise training and isoflavone supplementation maintain hip BMD
      compared to control, but these two interventions interfere with each other when
      combined. Isoflavone supplementation decreased LDL and adverse events related to
      menopausal symptoms.

PMID- 23165611
TI  - Effective perioperative management of multiple endocrine neoplasia type 1
      associated insulinomas.

PMID- 23165612
TI  - Comparative effectiveness of unfractionated and low-molecular-weight heparin for
      prevention of venous thromboembolism following bariatric surgery.
AB  - OBJECTIVE: To evaluate the effectiveness and safety of 3 predominant venous
      thromboembolism (VTE) prophylaxis strategies among patients undergoing bariatric
      surgery. DESIGN: Cohort study. SETTING: The Michigan Bariatric Surgery
      Collaborative, a statewide clinical registry and quality improvement program.
      PATIENTS: Twenty-four thousand seven hundred seventy-seven patients undergoing
      bariatric surgery between 2007 and 2012. INTERVENTIONS: Unfractionated heparin
      preoperatively and postoperatively (UF/UF), UF heparin preoperatively and low
      molecular-weight heparin postoperatively (UF/LMW), and LMW heparin preoperatively
      and postoperatively (LMW/LMW). MAIN OUTCOME MEASURES: Rates of VTE, hemorrhage,
      and serious hemorrhage (requiring >4 U of blood products or reoperation)
      occurring within 30 days of surgery. RESULTS: Overall, adjusted rates of VTE were
      significantly lower for the LMW/LMW (0.25%; P < .001) and UF/LMW (0.29%; P = .03)
      treatment groups compared with the UF/UF group (0.68%). While UF/LMW (0.22%; P =
      .006) and LMW/LMW (0.21%; P < .001) were similarly effective in patients at low
      risk of VTE (predicted risk <1%), LMW/LMW (1.46%; P = .10) seemed more effective
      than UF/LMW (2.36%; P = .90) for high-risk (predicted risk >=1%) patients. There
      were no significant differences in rates of hemorrhage or serious hemorrhage
      among the treatment strategies. CONCLUSION: Low-molecular-weight heparin is more
      effective than UF heparin for the prevention of postoperative VTE among patients
      undergoing bariatric surgery and does not increase rates of bleeding.

PMID- 23165613
TI  - Venous thromboembolism prophylaxis: one size does not fit all: comment on
      "Comparative effectiveness of unfractionated and low-molecular-weight heparin for
      prevention of venous thromboembolism following bariatric surgery".

PMID- 23165614
TI  - Association of postdischarge complications with reoperation and mortality in
      general surgery.
AB  - OBJECTIVES: To describe procedure-specific types, rates, and risk factors for
      postdischarge (PD) complications occurring within 30 days after 21 groups of
      inpatient general surgery procedures. DESIGN: Retrospective cohort study.
      SETTING: American College of Surgeons National Surgical Quality Improvement
      Program 2005 through 2010 Participant Use Data Files. PATIENTS: A total of
      551,510 adult patients who underwent one of 21 groups of general surgery
      procedures in the inpatient setting. MAIN OUTCOME MEASURES: Postdischarge
      complications, reoperation, and mortality. RESULTS: Of 551,510 patients (mean
      age, 54.6 years), 16.7% experienced a complication; 41.5% occurred PD. Of the PD
      complications, 75.0% occurred within 14 days PD. Proctectomy (14.5%), enteric
      fistula repair (12.6%), and pancreatic procedures (11.4%) had the highest PD
      complication rates. Breast, bariatric, and ventral hernia repair procedures had
      the highest proportions of complications that occurred PD (78.7%, 69.4%, and
      62.0%, respectively). For all procedures, surgical site complications,
      infections, and thromboembolic events were the most common. Occurrence of an
      inpatient complication increased the likelihood of a PD complication (12.5% vs
      6.2% without an inpatient complication; P < .001). Compared with patients without
      a PD complication, those with a PD complication had higher rates of reoperation
      (4.6% vs 17.9%, respectively; P < .001) and death (2.0% vs 6.9%, respectively; P
      < .001) within 30 days after surgery; those whose PD complication was preceded by
      an inpatient complication had the highest rates of reoperation (33.7%) and death
      (24.7%) (all P < .001). After adjustment, PD complications were associated with
      procedure type, American Society of Anesthesiologists class higher than 3, and
      steroid use. CONCLUSIONS: The PD complication rates vary by procedure, are
      commonly surgical site related, and are associated with mortality. Fastidious,
      procedure-specific patient triage at discharge as well as expedited patient
      follow-up could improve PD outcomes.

PMID- 23165615
TI  - Short-term outcomes after esophagectomy at 164 American College of Surgeons
      National Surgical Quality Improvement Program hospitals: effect of operative
      approach and hospital-level variation.
AB  - HYPOTHESIS: When assessing the effect of operative approach on outcomes, it may
      be less relevant whether a transhiatal or an Ivor Lewis esophagectomy was
      performed and may be more important to focus on patient selection and the quality
      of the hospital performing the operation. DESIGN: Observational study. SETTING:
      Hospitals participating in the American College of Surgeons National Surgical
      Quality Improvement Program. PATIENTS: Individuals undergoing esophagectomy were
      identified from January 1, 2005, to December 31, 2010. The following 4 groups
      were created based on operative approach: transhiatal, Ivor Lewis, 3-field, and
      any approach with an intestinal conduit. MAIN OUTCOME MEASURES: Risk-adjusted 30
      day outcomes and hospital-level variation in performance. RESULTS: At 164
      hospitals, 1738 patients underwent an esophageal resection: 710 (40.9%) were
      transhiatal, 497 (28.6%) were Ivor Lewis, 361 (20.8%) were 3-field, and 170
      (9.8%) were intestinal conduits. Compared with the transhiatal approach, Ivor
      Lewis esophagectomy was not associated with increased risk for postoperative
      complications; however, 3-field esophagectomy was associated with increased
      likelihood of postoperative pneumonia (odds ratio [OR], 1.88; 95% CI, 1.28-2.77)
      and prolonged ventilation exceeding 48 hours (OR, 1.68; 95% CI, 1.16-2.42).
      Intestinal conduit use was associated with increased 30-day mortality (OR, 2.65;
      95% CI, 1.08-6.47), prolonged ventilation exceeding 48 hours (OR, 1.61; 95% CI,
      1.01-2.54), and return to the operating room for any indication (OR, 1.85; 95%
      CI, 1.16-2.96). Patient characteristics were the strongest predictive factors for
      30-day mortality and serious morbidity. After case-mix adjustment, hospital
      performance varied by 161% for 30-day mortality and by 84% for serious morbidity.
      CONCLUSIONS: Compared with transhiatal dissection, Ivor Lewis esophagectomy did
      not result in worse postoperative complications. After controlling for case-mix,
      hospital performance varied widely for all outcomes assessed, indicating that
      reductions in short-term outcomes will likely result from expanding other aspects
      of hospital quality beyond a focus on specific technical maneuvers.

PMID- 23165617
TI  - Is insurance status a modifiable factor in brain tumor treatment outcomes?:
      comment on "Postoperative mortality after surgery for brain tumors by patient
      insurance status in the United States".

PMID- 23165616
TI  - Postoperative mortality after surgery for brain tumors by patient insurance
      status in the United States.
AB  - OBJECTIVE: To examine whether being uninsured is associated with higher in
      hospital postoperative mortality when undergoing surgery in the United States for
      a brain tumor. DESIGN: Retrospective cohort study using the Nationwide Inpatient
      Sample, January 1, 1999, through December 31, 2008. SETTING: The Nationwide
      Inpatient Sample contains all inpatient records from a stratified sample of 20%
      of hospitals in 37 states. PATIENTS: A total of 28,581 patients, aged 18 to 65
      years, who underwent craniotomy for a brain tumor. Three groups were studied:
      Medicaid recipients and privately insured and uninsured patients. MAIN OUTCOME
      MEASURE: The main outcome measure was in-hospital postoperative death.
      Associations between this outcome and insurance status were examined within the
      full cohort and within the subset of patients with no comorbidity using Cox
      proportional hazards models. These models were stratified by hospital to control
      for any clustering effects that could arise from differing access to care.
      RESULTS: In the unadjusted analysis, the mortality rate for privately insured
      patients was 1.3% (95% CI, 1.1%-1.4%) compared with 2.6% for uninsured patients
      (95% CI, 1.9%-3.3%; P < .001) and 2.3% for Medicaid recipients (95% CI, 1.8%
      2.8%; P < .001). After adjusting for patient characteristics and stratifying by
      hospital in patients with no comorbidity, uninsured patients still had a higher
      risk of experiencing in-hospital death (hazard ratio, 2.62; 95% CI, 1.11-6.14; P
      = .03) compared with privately insured patients. In this adjusted analysis, the
      disparity was not conclusively present in Medicaid recipients (hazard ratio,
      2.03; 95% CI, 0.97-4.23; P = .06). CONCLUSIONS: Uninsured patients who underwent
      craniotomy for a brain tumor experienced the highest in-hospital mortality.
      Differences in overall health do not fully account for this disparity.

PMID- 23165618
TI  - Irreversible electroporation for the ablation of liver tumors: are we there yet?
AB  - OBJECTIVE: To explore irreversible electroporation (IRE) as a novel, nonthermal
      form of tissue ablation using high-voltage electrical current to induce pores in
      the lipid bilayer of cells, resulting in cell death. DATA SOURCES: PubMed
      searches were performed using the keywords electroporation, IRE, and ablation.
      The abstracts for the 2012 meetings of both the American Hepato-Pancreato-Biliary
      Association and the Society for Interventional Radiology were also searched. All
      articles and abstracts with any reference to electroporation were identified and
      reviewed. STUDY SELECTION: All studies and abstracts pertaining to
      electroporation. DATA EXTRACTION: All data pertaining to the safety and efficacy
      of IRE were extracted from preclinical and clinical studies. Preclinical data
      detailing the theory and design of IRE systems were also extracted. DATA
      SYNTHESIS: Preclinical studies have suggested that IRE may have advantages over
      conventional forms of thermal tumor ablation including no heat sink effect and
      preservation of the acellular elements of tissue, resulting in less unwanted
      collateral damage. The early clinical experience with IRE demonstrates safety for
      the ablation of human liver tumors. Short-term data regarding oncologic outcome
      is now emerging and appears encouraging. CONCLUSION: Irreversible electroporation
      is likely to fill a niche void for the ablation of small liver tumors abutting a
      major vascular structure and for ablation of tumors abutting a major portal
      pedicle where heat sink and collateral damage must be avoided for maximum
      efficacy and safety. Studies are still needed to define the short-term and long
      term oncologic efficacy of IRE.

PMID- 23165619
TI  - Another club in the bag: comment on "Irreversible electroporation for the
      ablation of liver tumors".

PMID- 23165620
TI  - Image of the month. PNET of the pancreas.

PMID- 23165622
TI  - Image of the month. Hernia containing omentum and right gastroepiploic artery.

PMID- 23165624
TI  - Publication of postdischarge and readmission complications: failure, folly, or
      funding opportunity?: comment on "Association of postdischarge complications with
      reoperation and mortality in general surgery".

PMID- 23165625
TI  - A VUV photoionization study of the multichannel reaction of phenyl radicals with
      1,3-butadiene under combustion relevant conditions.
AB  - We studied the reaction of phenyl radicals (C(6)H(5)) with 1,3-butadiene
      (H(2)CCHCHCH(2)) exploiting a high temperature chemical reactor under combustion
      like conditions (300 Torr, 873 K). The reaction products were probed in a
      supersonic beam by utilizing VUV radiation from the Advanced Light Source and by
      recording the experimental PIE curves at mass-to-charge ratios of m/z = 130
      (C(10)H(10)(+)), 116 (C(9)H(8)(+)), and 104 (C(8)H(8)(+)). Our data suggest that
      the atomic hydrogen (H), methyl (CH(3)), and vinyl (C(2)H(3)) losses are open
      with estimated branching ratios of about 86 +/- 4%, 8 +/- 2%, and 6 +/- 2%,
      respectively. The isomer distributions were probed further by fitting the
      experimentally recorded PIE curves with a linear combination of the PIE curves of
      individual C(10)H(10), C(9)H(8), and C(8)H(8) isomers. These fits indicate the
      formation of three C(10)H(10) isomers (trans-1,3-butadienylbenzene, 1,4
      dihydronaphthalene, 1-methylindene), three C(9)H(8) isomers (indene,
      phenylallene, 1-phenyl-1-methylacetylene), and a C(8)H(8) isomer (styrene). A
      comparison with results from recent crossed molecular beam studies of the 1,3
      butadiene-phenyl radical reaction and electronic structure calculations suggests
      that trans-1,3-butadienylbenzene (130 amu), 1,4-dihydronaphthalene (130 amu), and
      styrene (104 amu) are reaction products formed as a consequence of a bimolecular
      reaction between the phenyl radical and 1,3-butadiene. 1-Methylindene (130 amu),
      indene (116 amu), phenylallene (116 amu), and 1-phenyl-1-methylacetylene (116
      amu) are synthesized upon reaction of the phenyl radical with three C(4)H(6)
      isomers: 1,2-butadiene (H(2)CCCH(CH(3))), 1-butyne (HCCC(2)H(5)), and 2-butyne
      (CH(3)CCCH(3)); these C(4)H(6) isomers can be formed from 1,3-butadiene via
      hydrogen atom assisted isomerization reactions or via thermal rearrangements of
      1,3-butadiene involving hydrogen shifts in the high temperature chemical reactor.

PMID- 23165627
TI  - First paramagnetic Pd(II) complex with a PdN4S2 coordination core.
AB  - Reaction of the potassium salt of N-thiophosphorylated thiourea 2
      PyNHC(S)NHP(S)(OiPr)(2) (HL) with PdCl(2) in aqueous MeOH leads to the formation
      of two mononuclear homoleptic complexes [Pd{2-PyNHC(S)NP(S)(OiPr)(2)-1,5
      S,S'}(2)] ([Pd(L-1,5-S,S')(2)]) and [Pd{2-PyNHC(S)NP(S)(OiPr)(2)-1,5,7
      N,N',S}(2)] ([Pd(L-1,5,7-N,N',S)(2)]), while the mechanically induced solid-state
      reaction of KL and PdCl(2) leads to the exclusive formation of [Pd(L-1,5,7
      N,N',S)(2)]. The dithiocoordinated desmotrope is square-planar and diamagnetic,
      while the second desmotrope is unprecedentedly octahedrally configured and
      paramagnetic.

PMID- 23165626
TI  - Expression of integrin alpha2 receptor in human cord blood CD34+CD38-CD90+ stem
      cells engrafting long-term in NOD/SCID-IL2Rgamma(c) null mice.
AB  - Human hematopoietic stem cells reside in the CD34+CD38-CD90+ population in cord
      blood and bone marrow. However, this cell fraction is heterogeneous, and the
      phenotype of the rare primitive stem cells remains poorly defined. We here report
      that primitive cord blood CD34+CD38-CD90+ stem cells, with the ability to
      reconstitute NOD/SCID-IL2Rgamma(c) null (NSG) mice long-term, at 24 weeks after
      transplantation, can be prospectively isolated at an increased purity by using
      integrin alpha2 receptor as an additional stem cell marker. Using a limiting
      dilution transplantation assay, we found a highly significant enrichment of
      multilineage reconstituting stem cells in the CD34+CD38-CD90+ cell fraction
      expressing the integrin alpha2 receptor, with a frequency of 1/29 cells, as
      compared to a frequency of 1/157 in the corresponding integrin alpha2- cells. In
      line with this, long-term reconstituting stem cells within the cord blood
      CD34+CD38- cell population were significantly enriched in the integrin alpha2+
      fraction, while stem cells and progenitors reconstituting short-term, at 8-12
      weeks, were heterogeneous in integrin alpha2 expression. Global gene expression
      profiling revealed that the lineage-marker negative (Lin-) CD34+CD38-CD90+CD45RA-
      integrin alpha2+ cell population was molecularly distinct from the integrin
      alpha2- cell population and the more mature Lin-CD34+CD38-CD90-CD45RA- cell
      population. Our findings identify integrin alpha2 as a novel stem cell marker,
      which improves prospective isolation of the primitive human hematopoietic stem
      cells within the CD34+CD38-CD90+ cell population for experimental and therapeutic
      stem cell applications.

PMID- 23165628
TI  - Expression of LRIG1 and LRIG3 correlates with human papillomavirus status and
      patient survival in cervical adenocarcinoma.
AB  - The incidence of cervical adenocarcinoma, which accounts for 10-20% of all
      cervical cancers, has increased continuously in developed countries during the
      last two decades, unlike squamous cell cervical carcinoma. This increasing trend,
      noted particularly among women under the age of 40 years, has occurred despite
      extensive cytological Pap smear screening. A deeper understanding of the etiology
      of cervical adenocarcinoma, better preventive measures and reliable prognostic
      markers are urgently needed. The human leucine-rich repeats and immunoglobulin
      like domains (LRIG) gene family includes: LRIG1, LRIG2 and LRIG3. LRIG expression
      has proven to be of prognostic value in different types of human cancers,
      including breast cancer, early stage invasive squamous cervical cancer, cutaneous
      squamous cell carcinoma, oligodendroglioma and astrocytoma. LRIG1 functions as a
      tumor suppressor, while less is known about the functions of LRIG2 and LRIG3.
      This study evaluated the expression of the three LRIG proteins in tumor specimens
      from 86 women with pure cervical adenocarcinoma by immunohistochemistry. Possible
      correlations between LRIG expression and known prognostic factors, including
      human papillomavirus (HPV) status, FIGO stage and histology were investigated.
      Patient survival data were collected retrospectively and the possible prognostic
      value of LRIG protein expression was investigated. High staining intensity of
      LRIG1 and high fraction of LRIG3-positive cells were significantly associated
      with patient survival, and positive correlations were found between LRIG1 and
      LRIG3 staining intensity and HPV status. Thus, the LRIG proteins may be important
      determinants of cervical adenocarcinoma progression and their diagnostic and
      prognostic potential should be studied further.

PMID- 23165629
TI  - [Vaccinations in the prison environment].

PMID- 23165630
TI  - [Study of the prevalence of severe mental disorder in the penitentiaries Puerto
      I, II and III of Puerto de Santa Maria (Cadiz): new strategies of psychiatric
      care in prison].
AB  - INTRODUCTION: In recent years it has been observed that there is a high level of
      severe mental disorder within the Spanish prison system. METHODS AND MATERIALS: A
      one year descriptive and transversal study of the psychiatric health care demand
      in the prisons Puerto I, II and III of Puerto de Santa Maria (Cadiz). RESULTS: Of
      the 128 patients studied, the psychiatric diagnostics with highest prevalence
      were personality disorders (F60-69) at 35.16%, the next group was psychosis (F20
      29) at 25.78%, and in third place mental and behaviour disorders due to use of
      psychotropic substances (F10-19) at 16.41%. 46.09% suffered conditions which are
      categorised as severe mental disorders. DISCUSSION: This study confirms the high
      levels of severe mental disorder in prisons located in the area of the Puerto
      Real Hospital. We are making efforts to improve on psychiatric health care
      provided to these patients by working closely with the Prison system.

PMID- 23165631
TI  - [Evolution of the need and coverage of syringe exchange programs in Spanish
      prisons, 1992-2009: A revised estimation].
AB  - INTRODUCTION: The objective of this paper is to amend the bias included in our
      previous work, presenting a corrected estimation of the need and coverage of
      syringes/needles in Spanish prisons between 1992 and 2009. METHODS: Data on the
      provision of the needles exchange programs (NEPs) in prison is taken from
      official publications. The need was calculated by applying multiplicative methods
      to secondary data from several sources. Coverage was estimated as the quotient
      between provision and need and the difference between these magnitudes. The
      detected need estimate bias has been corrected. RESULTS: NEP's in prisons started
      in 1997. Their maximum coverage reached 36% in 2005, which is much higher than
      the initially estimated value. However, it decreased by half in the next four
      years, reaching 17.4% in 2009. CONCLUSION: The remarkable coverage reached by
      these programmes must be valued, but more recent evolution leads us to emphasize
      the need to be imaginative so that new epidemiological and economic circumstances
      do not lead to their disappearance.

PMID- 23165632
TI  - [A new prison health care model: the experience of the Basque Country].
AB  - A year after the transfer of prison health care functions and services from the
      State Administration to the Autonomous Community of the Basque Country, the
      process up to completion of the transfer, the current status of the transferred
      services and remaining challenges are described.

PMID- 23165633
TI  - [Vaccination in the prison population: a review].
AB  - From the first day in prison, convicts are exposed to several types of diseases,
      many of which can be prevented by vaccination. During captivity, the risk of
      acquiring these types of diseases is known to be higher than outside prison. This
      increased risk can be explained by structural and logistical factors in prison,
      as well as by acquired behaviour before and during captivity. Furthermore, for
      many prisoners captivity is an opportunity to access the health care system and
      therefore a chance to update their adult vaccination status. The traditional
      concept suggesting that prisons are primarily designed to ensure public safety
      should be complemented by this aspect of health, which is a broader approach to
      public safety.

PMID- 23165634
TI  - [Overcrowding in prisons and its impact on health].
AB  - Overcrowding in prisons is a common problem that affects many countries. It is
      difficult to define this term because there is no single internationally accepted
      standard. However, this is a situation that must be counteracted, because
      people's behaviour can be affected to the extent that it leads to self-harm or
      violent behaviour to others. But prison overcrowding also has other effects on
      the health and well being of the people living in these conditions and may also
      adversely affect public health and the prison system. It can increase the
      prevalence of diseases, particularly infectious and psychiatric disorders. It may
      also hinder the work of social rehabilitation and lead to inhuman, cruel or
      degrading treatment. This paper reviews the scant literature about overcrowding
      in prisons. Increasing awareness about the issue in the international community
      and prison administrations and above all, assigning specific economic resources,
      are key elements in preventing this deficit in social welfare and health care.

PMID- 23165636
TI  - [Comments on the article: Evolution of the need and coverage of opioid
      substitution and needle exchange programs in Spanish, 1992-2009].

PMID- 23165635
TI  - [Comments on the article: Evolution of the need and coverage of opioid
      substitution and needle exchange programs in Spanish, 1992-2009].

PMID- 23165638
TI  - Reversible intramolecular coupling of the terminal borylene and a carbonyl ligand
      of [Cp(CO)2Mn=B-tBu].
AB  - Cyclic complex 2 with bridging carbonyl ligands was synthesized from a facile and
      reversible intermolecular carbonyl-borylene ligand coupling reaction at room
      temperature. Complex 2 exhibits an unprecedented coordination mode for boron
      metal complexes, which is also reflected in its remarkable (11)B NMR chemical
      shift of -57.2 ppm. Findings from spectroscopic, X-ray, and computational studies
      are presented, along with a proposed mechanism.

PMID- 23165639
TI  - A homoleptic tetravalent cerium silylamide.
AB  - Treatment of Ce[N(SiHMe(2))(2)](3)(thf)(2) with the chlorinating agents PhICl(2),
      Ph(3)CCl or C(2)Cl(6) gave the homoleptic Ce(IV) silylamide
      Ce[N(SiHMe(2))(2)](4). When performed in the absence of donating (solvent)
      molecules, the trivalent cluster Ce(5)[N(SiHMe(2))(2)](8)Cl(7) was isolated.

PMID- 23165641
TI  - Guest covalent capture by a host: a biomimetic strategy for the selective
      functionalization of a cavity.
AB  - A biomimetic strategy for the monofunctionalization of a calix[6]arene core is
      described. It is based on host-guest chemistry (mimicking the Michaelis-Menten
      adduct in enzymes) and allows the finely tuned pre-organization of the substrate
      (an alkyne) with respect to the reactant (three azido groups introduced at the
      calixarene large rim). It is shown that the thermal Huisgen reaction implemented
      in this work proceeds under very mild conditions with total regioselectivity of
      the cycloaddition process. The scope of the reaction was explored and the results
      suggest that such a supramolecular strategy is quite versatile and could be
      applied to the selective functionalization of other cavitands bearing different
      recognition patterns. A detailed structural, thermodynamic, and kinetic study is
      also reported, highlighting interesting biomimetic features: The importance of
      the host-guest adduct strength, the high sensitivity of the reaction to the pre
      organization of the reactive partners (alkyne vs. azide), and a significant
      impact of the embedment on the transition state. The self-coordination of the
      monofunctionalized products was also studied and an "endo/exo" switch of the
      internal side-chain could be triggered by adding competitive ligands.

PMID- 23165642
TI  - Platinum complexes bearing a boron-based PBP pincer ligand: synthesis, structure,
      and application as a catalyst for hydrosilylation of 1-decene.
AB  - Four platinum(II) complexes bearing a boron-based PBP pincer ligand and chloride,
      hydride, triflate, and bis(trifluoromethanesulfonyl)imide were synthesized and
      structurally characterized. PBP-platinum chloride was proven to be an active
      catalyst for the hydrosilylation reaction using 1-decene and triethylsilane.

PMID- 23165643
TI  - Quantitative magnetic resonance imaging can distinguish remodeling mechanisms
      after acute myocardial infarction based on the severity of ischemic insult.
AB  - The type and extent of myocardial infarction encountered clinically is primarily
      determined by the severity of the initial ischemic insult. The purpose of the
      study was to differentiate longitudinal fluctuations in remodeling mechanisms in
      porcine myocardium following different ischemic insult durations. Animals (N = 8)
      were subjected to coronary balloon occlusion for either 90 or 45 min, followed by
      reperfusion. Imaging was performed on a 3 T MRI scanner between day-2 and week-6
      postinfarction with edema quantified by T2, hemorrhage by T2*, vasodilatory
      function by blood-oxygenation-level-dependent T2 alterations and
      infarction/microvascular obstruction by contrast-enhanced imaging. The 90-min
      model produced large transmural infarcts with hemorrhage and microvascular
      obstruction, while the 45 min produced small nontransmural and nonhemorrhagic
      infarction. In the 90-min group, elevation of end-diastolic-volume, reduced
      cardiac function, persistence of edema, and prolonged vasodilatory dysfunction
      were all indicative of adverse remodeling; in contrast, the 45-min group showed
      no signs of adverse remodeling. The 45- and 90-min porcine models seem to be
      ideal for representing the low- and high-risk patient groups, respectively,
      commonly encountered in the clinic. Such in vivo characterization will be a key
      in predicting functional recovery and may potentially allow evaluation of novel
      therapies targeted to alleviate ischemic injury and prevent microvascular
      obstruction/hemorrhage.

PMID- 23165644
TI  - Development of super-dense transfected cell microarrays generated by
      piezoelectric inkjet printing.
AB  - Super-dense transfected cell microarrays (TCMs) were created by a piezoelectric
      inkjet printer on a glass substrate that had been grafted with poly(ethylene
      glycol) (PEG). The micro-spots that contained plasmid and extra-cellular matrix
      (ECM) protein were separated from one another by a hydrophilic barrier generated
      by PEG. We successfully constructed the densest TCMs with spots of 50 MUm in
      diameter and 150 MUm in pitch.

PMID- 23165645
TI  - Floating-Harbor syndrome and polycystic kidneys associated with SRCAP mutation.
AB  - Floating-Harbor syndrome (FHS) is a rare genetic disorder recently shown to be
      caused by mutations in the Snf2-related CREB-binding protein activator protein
      gene (SRCAP). It comprises three key clinical features of characteristic facies,
      expressive and receptive speech impairment and short stature. We report on a
      patient with this syndrome associated with early adult-onset hypertension and
      bilateral polycystic kidneys. Family screening for polycystic kidney disease was
      negative and mutations in polycystic kidney disease 1 and 2 genes (PKD1 and PKD2)
      were absent. Sequencing of the SRCAP gene demonstrated a de novo mutation
      matching one of the known FHS-associated mutations. The patient required
      treatment with anti-hypertensives and will require lifelong renal monitoring. We
      suggest this patient's presentation may be due to the pleiotropic effects of
      SRCAP mutations. Further, the protein encoded by SRCAP is known to interact with
      CREB-binding protein, the product of the gene mutated in Rubinstein-Taybi
      syndrome, which is associated with renal abnormalities. A literature review of
      the renal findings in patients with Floating-Harbor syndrome identified another
      patient with possible polycystic kidneys, two patients with early onset
      hypertension, and a young patient with a ruptured intracranial aneurysm, which
      can be a feature of classic adult polycystic kidney disease. Collectively, these
      findings suggest that all patients with Floating-Harbor syndrome should undergo
      regular blood pressure monitoring and screening for polycystic kidneys by
      ultrasound at the time of the FHS diagnosis with imaging to be repeated during
      adulthood if a childhood ultrasound was negative.

PMID- 23165647
TI  - Sports performance research under the spotlight.

PMID- 23165646
TI  - Biodegradable internal fixation plates enabled with X-ray visibility by a
      radiopaque layer of beta-tricalcium phosphate and poly (lactic-co-glycolic acid).
AB  - Biodegradable polymer plates can be clinically used as an alternative to metal
      plates (e.g., titanium) for internal fixation, which, however, are not visible
      with X-ray imaging, often used for post-operative diagnostics. In this study,
      therefore, we prepared a biodegradable plate enabled with X-ray visibility by
      attaching a radiopaque layer on a biodegradable fixation plate in clinical use
      (Inion, Finland). A radiopaque layer was made of a fine powder of a radiopaque
      agent, beta-tricalcium phosphate (TCP) and a biodegradable binder material, poly
      (lactic-co-glycolic acid) (PLGA), which were physically mixed without change in
      their chemical structure. The radiopacity increased as we increased the layer
      thicknesses from 0.5 mm to 1.3 mm. Regardless of layer thickness, however, the
      radiopacity decreased with time both in vitro and in vivo due to decreasing
      density of TCP in the layer by swelling and degradation of a binder material,
      PLGA. The in vivo study with rabbits revealed that a discernible image of the
      radiopaque plate could be obtained by X-ray for up to 21 days, also showing the
      overall biocompatibility 6 months after implantation. Therefore, we conclude that
      the radiopaque plate prepared in this work is a promising fixation device enabled
      with both X-ray visibility and biodegradability.

PMID- 23165648
TI  - p53 as a target in myeloproliferative neoplasms.

PMID- 23165649
TI  - Administer tranexamic acid early to injured patients at risk of substantial
      bleeding.

PMID- 23165650
TI  - Doctor is allowed back to work after five year suspension with 16 conditions on
      his registration.

PMID- 23165651
TI  - Competition in NHS is driving patients towards private providers.

PMID- 23165652
TI  - MYC expression and distribution in normal mature lymphoid cells.
AB  - The distribution of the product of the proto-oncogene MYC in lymphoid tissue has
      not been established in three decades, due to a combination of factors including
      low abundance, short half-life, and antibody sensitivity and specificity. We
      sought to validate antibodies in order to define the expression and distribution
      of MYC in mature normal lymphoid cells by multiparametric immunophenotyping.
      Having validated two antibodies for flow cytometry and for immunohistochemistry,
      we analysed normal tonsil tissue. MYC is expressed predominantly in B cells, some
      of which are interfollicular large, activated, and cycling CD30+, IRF4+, AID+/-
      blasts. Follicular mantle, isotype-switched memory B cells and FcRH4/IRTA1+ B
      cells express MYC in a wide range of levels and are small non-proliferating
      CDKN1B/p27-positive or -negative resting B lymphocytes. Germinal centre founder
      cells, CD30+ BCL6+/- AID+/- germinal centre blasts, and a population of GC cells
      in the apical light zone express MYC. MYC is expressed in all phases of the cell
      cycle in activated and mature B cells, but rarely in other lymphoid types and
      only partially fulfils the predictions derived from extractive and ex vivo
      experiments of the past 30 years.

PMID- 23165653
TI  - Ethyl acetate extraction from a Chinese herbal formula, Jiedu Xiaozheng Yin,
      inhibits the proliferation of hepatocellular carcinoma cells via induction of
      G0/G1 phase arrest in vivo and in vitro.
AB  - Jiedu Xiaozheng Yin (JXY), a polyherbal formula of traditional Chinese medicine
      (TCM), has been used to treat various kinds of cancer in China. However, the
      mechanism of its anticancer activity has yet to be elucidated. Air-dried herbs
      were extracted with reagents of different polarity. HepG2 cells were treated with
      different doses of ethyl acetate extract (EE-JXY) and chloroform extract (CE-JXY)
      for 24 h. Cell viability was detected by MTT assay. Colony formation ability was
      also evaluated. Cell cycle was evaluated by FACS. Tumor bearing BALB/c nude mice
      was treated with EE-JXY (0.06 g/kg) for 20 days. Tumor volume and weight were
      monitored. The percentage of PCNA-positive cells and the level of G1 phase
      proteins [cyclin-dependent kinase2 (CDK2), cyclin-dependent kinase4 (CDK4),
      cyclin D and cyclin E and G2 phase proteins [cyclin-dependent kinase1 (CDK1),
      cyclin A and cyclin B] were detected by immunohistochemistry and western
      blotting. EE-JXY and CE-JXY dose-dependently inhibited the growth of HepG2 cells
      (P<0.01 for both). Furthermore, EE-JXY inhibited the formation of cell colonies
      and blocked the cell cycle to G1 phase in a dose-dependent manner (P<0.01 for
      all). EE-JXY showed an obviously antitumor effect in vivo (P<0.05). Further
      investigation showed that EE-JXY decreased the proliferation index of tumors
      (P<0.01) through increasing the expression of G1-related proteins (cyclin D and
      cyclin E, P<0.05 and P<0.01). These results suggested that JXY inhibits the
      growth of HepG2 cells at least via arresting the cell cycle at the G0/G1 phase.

PMID- 23165654
TI  - Effect of maintenance immunosuppressive drugs on virus pathobiology: evidence and
      potential mechanisms.
AB  - Recent evidence suggesting a potential anti-CMV effect of mTORis is of great
      interest to the transplant community. However, the concept of an
      immunosuppressant with antiviral properties is not new, with many accounts of the
      antiviral properties of several agents over the years. Despite these reports, to
      date, there has been little effort to collate the evidence into a fuller picture.
      This manuscript was developed to gather the evidence of antiviral activity of the
      agents that comprise a typical immunosuppressive regimen against viruses that
      commonly reactivate following transplant (HHV1 and 2, VZV, EBV, CMV and HHV6, 7,
      and 8, HCV, HBV, BKV, HIV, HPV, and parvovirus). Appropriate immunosuppressive
      regimens posttransplant that avoid acute rejection while reducing risk of viral
      reactivation are also reviewed. The existing literature was disparate in nature,
      although indicating a possible stimulatory effect of tacrolimus on BKV,
      potentiation of viral reactivation by steroids, and a potential advantage of
      mammalian target of rapamycin (mTOR) inhibition in several viral infections,
      including BKV, HPV, and several herpesviruses.

PMID- 23165655
TI  - Mechanistic aspects of the linear stabilization of non-stationary electrochemical
      oscillations.
AB  - The problem of non-stationarity in experimentally recorded time-series is common
      in many (electro)chemical systems. Underlying this non-stationarity is the slow
      drift in some uncontrollable parameter, and it occurs in spite of the fact that
      all controllable parameters are kept constant. Particularly for electrochemical
      systems, some of us have recently suggested [J. Phys. Chem. C, 144, (2010), 22262
      22268] an empirical method to stabilize experimental time-series. The method was
      exemplified for the electro-oxidation of methanol and different patterns were
      satisfactorily stabilized. In this paper we further elaborate some mechanistic
      aspects of this method and test it for the electro-oxidation of formaldehyde, a
      system that has some resemblance with the electro-oxidation of methanol, but
      produces a richer dynamics. In terms of the reaction mechanism, we were able to
      describe the coupling and to separate the surface processes of the two sub
      systems: the fast one (or the core-oscillator) and the slow one, responsible for
      the drift.

PMID- 23165656
TI  - Cost-effectiveness of bazedoxifene compared with raloxifene in the treatment of
      postmenopausal osteoporotic women.
AB  - Bazedoxifene is a novel selective estrogen receptor modulator (SERM) for the
      prevention and treatment of osteoporosis. In addition to the therapeutic value of
      a new agent, evaluation of the cost-effectiveness compared with relevant
      alternative treatment(s) is an important consideration to facilitate healthcare
      decision making. This study evaluated the cost-effectiveness of bazedoxifene
      compared with raloxifene for the treatment of postmenopausal women with
      osteoporosis. The cost-effectiveness of treatment for 3 years with bazedoxifene
      was compared with raloxifene using an updated version of a previously validated
      Markov microsimulation model. Analyses were conducted from a Belgian healthcare
      payer perspective and, the base-case population was women (aged 70 years) with
      bone mineral density T-score <= -2.5. The effects of bazedoxifene and raloxifene
      on fracture risk were derived from the 3-year results of a randomized, double
      blind, placebo-controlled and active-controlled study, including postmenopausal
      women with osteoporosis. The cost-effectiveness analysis based on efficacy data
      from the overall clinical trial indicated that bazedoxifene and raloxifene were
      equally cost-effective. When the results were examined based on the subgroup
      analysis of women at higher risk of fractures, bazedoxifene was dominant (lower
      cost for higher effectiveness) compared with raloxifene in most of the
      simulations. Sensitivity analyses confirmed the robustness of the results, which
      were largely independent of starting age of treatment, fracture risk, cost, and
      disutility. In addition, when the cost of raloxifene was reduced by one-half or
      when incorporating the raloxifene effects on reducing breast cancer, bazedoxifene
      remained cost-effective, at a threshold of ?35,000 per quality-adjusted life
      years gained, in 85% and 68% of the simulations, respectively. Under the
      assumption of improved antifracture efficacy of bazedoxifene over raloxifene in
      women with high risk of fractures, this study suggests that bazedoxifene can be
      considered cost-effective, and even dominant, when compared with raloxifene in
      the treatment of postmenopausal osteoporotic women.

PMID- 23165657
TI  - Stratum corneum drying drives vertical compression and lipid organization and
      improves barrier function in vitro.
AB  - The stratum corneum dehydrates after exogenous hydration due to skincare or
      bathing. In this study, sheets of stratum corneum were isolated from
      reconstructed human epidermis and the barrier function and structure of these
      sheets were assessed during drying with the aim of improving our understanding of
      skincare. Water diffusion through the sheets of stratum corneum decreased with
      drying, accompanied by decreased thickness and increased visible light
      transmission through the sheets. Electron paramagnetic resonance revealed that
      the order parameter values of stratum corneum lipids increased with drying. X-ray
      diffraction analysis revealed increases in the diffraction intensity of lamellar
      structures, with an 11-12 nm periodicity and spacing of 0.42 nm for lattice
      structures with drying. These results suggest that the drying process improves
      the barrier function of the stratum corneum by organizing the intercellular
      lipids in a vertically compressed arrangement.

PMID- 23165658
TI  - Ephrin-A3 suppresses Wnt signaling to control retinal stem cell potency.
AB  - The ciliary epithelium (CE) of adult mammals has been reported to provide a
      source of retinal stem cells (RSCs) that can give rise to all retinal cell types
      in vitro. A recent study, however, suggests that CE-derived cells possess
      properties of pigmented ciliary epithelial cells and display little neurogenic
      potential. Here we show that the neurogenic potential of CE-derived cells is
      negatively regulated by ephrin-A3, which is upregulated in the CE of postnatal
      mice and presents a strong prohibitory niche for adult RSCs. Addition of ephrin
      A3 inhibits proliferation of CE-derived RSCs and increases pigment 349 cell 359.
      In contrast, absence of ephrin-A3 promotes proliferation and increases expression
      of neural progenitor cell markers and photoreceptor progeny. The negative effects
      of ephrin-A3 on CE-derived RSCs are mediated through activation of an EphA4
      receptor and suppression of Wnt3a/beta-catenin signaling. Together, our data
      suggest that CE-derived RSCs contain the intrinsic machinery to generate
      photoreceptors and other retinal neurons, while the CE of adult mice expresses
      negative regulators that prohibit the proliferation and neural differentiation of
      RSCs. Manipulating ephrin and Wnt/beta-catenin signaling may, thus, represent a
      viable approach in activating the endogenous neurogenic potential of CE-derived
      RSCs for treating photoreceptor damage and retinal degenerative disorders.

PMID- 23165659
TI  - Effect of testosterone replacement on response to sildenafil citrate in men with
      erectile dysfunction: a parallel, randomized trial.
AB  - BACKGROUND: Erectile dysfunction and low testosterone levels frequently occur
      together. OBJECTIVE: To determine whether addition of testosterone to sildenafil
      therapy improves erectile response in men with erectile dysfunction and low
      testosterone levels. DESIGN: Randomized, double-blind, parallel, placebo
      controlled trial. (ClinicalTrials.gov registration number: NCT00512707) SETTING:
      Outpatient academic research center. PARTICIPANTS: Men aged 40 to 70 years with
      scores of 25 or less for the erectile function domain (EFD) of the International
      Index of Erectile Function, total testosterone levels less than 11.45 nmol/L
      (<330 ng/dL), or free testosterone levels less than 173.35 pmol/L (<50 pg/mL).
      INTERVENTION: Sildenafil dose was optimized, and 140 participants were then
      randomly assigned to 14 weeks of daily transdermal gel that contained 10-g
      testosterone for 70 participants and placebo for the remaining 70 participants.
      All participants were included in the primary analysis, although 10 in the
      testosterone group and 12 in the placebo group did not complete the study.
      RESULTS: At baseline, the 2 groups had similar EFD scores. Administration of
      sildenafil alone was associated with a substantial increase in EFD score (mean,
      7.7 [95% CI, 6.5 to 8.8]), but change in EFD score after randomization did not
      differ between the groups (difference, 2.2 [CI, -0.8 to 5.1]; P = 0.150). The
      findings were similar for other domains of sexual function in younger men, more
      obese men, and men with lower baseline testosterone levels or an inadequate
      response to sildenafil alone. Frequency of adverse events was similar for
      testosterone and placebo groups. LIMITATION: Whether testosterone could improve
      erectile function without sildenafil was not studied. CONCLUSION: Sildenafil plus
      testosterone was not superior to sildenafil plus placebo in improving erectile
      function in men with erectile dysfunction and low testosterone levels. PRIMARY
      FUNDING SOURCE: National Institute of Child Health and Human Development.

PMID- 23165661
TI  - Pharmacy dispensing of electronically discontinued medications.
AB  - BACKGROUND: Most physician offices do not transmit orders for medication
      discontinuation to the pharmacy, creating the potential for errors in dispensing
      of previously prescribed medications. Electronic health records offer the
      potential to assess this patient safety concern. OBJECTIVE: To assess the
      frequency of and potential patient harm associated with pharmacy dispensing of
      discontinued medications in the ambulatory setting. DESIGN: Retrospective cohort
      study. SETTING: Multispecialty group practice in eastern Massachusetts using an
      electronic health record. PATIENTS: 30 406 adult patients with an electronic
      discontinuation order for antihypertensive, antiplatelet, anticoagulant, oral
      hypoglycemic, and statin medications between November 2008 and October 2009.
      MEASUREMENTS: Dispensing of discontinued medications within 12 months and
      associated potential patient harm. RESULTS: Among 83 902 targeted medications
      that were electronically discontinued, 1218 (1.5% [95% CI, 1.4% to 1.5%]) were
      subsequently dispensed by the pharmacy a mean of 1.0 (SD, 0.3) time during the 12
      month follow-up. Among the top 10 most frequently electronically discontinued
      medications, the rate of subsequent dispensing by a pharmacy ranged from 0.9% for
      metformin to 2.5% for metoprolol. Manual chart review of 416 medication
      dispensing events that were predefined as high risk according to an automated
      algorithm identified potential harm in 50 (12%) cases, including clinical
      reactions (n = 18), laboratory abnormalities (n = 17), duplicated medication
      classes dispensed (n = 8), and potential allergic reactions (n = 7). LIMITATION:
      Information on pharmacy dispensing was available for only 52% of medication
      orders. CONCLUSION: The dispensing of discontinued medications represents an
      important ambulatory patient safety concern. Electronic health records should be
      used to facilitate better communication between providers and pharmacies and
      improve medication safety. PRIMARY FUNDING SOURCE: National Institutes of Health.

PMID- 23165660
TI  - Effects of an intervention to increase bed alarm use to prevent falls in
      hospitalized patients: a cluster randomized trial.
AB  - BACKGROUND: Bed alarm systems intended to prevent hospital falls have not been
      formally evaluated. OBJECTIVE: To investigate whether an intervention aimed at
      increasing bed alarm use decreases hospital falls and related events. DESIGN:
      Pair-matched, cluster randomized trial over 18 months. Nursing units were
      allocated by computer-generated randomization on the basis of baseline fall
      rates. Patients and outcome assessors were blinded to unit assignment; outcome
      assessors may have become unblinded. (ClinicalTrials.gov registration number:
      NCT00183053) SETTING: 16 nursing units in an urban community hospital. PATIENTS:
      27 672 inpatients in general medical, surgical, and specialty units.
      INTERVENTION: Education, training, and technical support to promote use of a
      standard bed alarm system (intervention units); bed alarms available but not
      formally promoted or supported (control units). MEASUREMENTS: Pre-post difference
      in change in falls per 1000 patient-days (primary end point); number of patients
      who fell, fall-related injuries, and number of patients restrained (secondary end
      points). RESULTS: Prevalence of alarm use was 64.41 days per 1000 patient-days on
      intervention units and 1.79 days per 1000 patient-days on control units (P =
      0.004). There was no difference in change in fall rates per 1000 patient-days
      (risk ratio, 1.09 [95% CI, 0.85 to 1.53]; difference, 0.41 [CI, -1.05 to 2.47],
      which corresponds to a greater difference in falls in control vs. intervention
      units) or in the number of patients who fell, injurious fall rates, or the number
      of patients physically restrained on intervention units compared with control
      units. LIMITATION: The study was conducted at a single site and was slightly
      underpowered compared with the initial design. CONCLUSION: An intervention
      designed to increase bed alarm use in an urban hospital increased alarm use but
      had no statistically or clinically significant effect on fall-related events or
      physical restraint use. PRIMARY FUNDING SOURCE: National Institute on Aging.

PMID- 23165662
TI  - Screening for HIV: systematic review to update the 2005 U.S. Preventive Services
      Task Force recommendation.
AB  - BACKGROUND: A 2005 U.S. Preventive Services Task Force (USPSTF) review found good
      evidence that HIV screening is accurate and that antiretroviral therapy (ART) for
      immunologically advanced disease is associated with substantial clinical
      benefits, but insufficient evidence to determine the effects on transmission or
      in less immunologically advanced disease. PURPOSE: To update the 2005 USPSTF
      review on benefits and harms of HIV screening in adolescents and adults, focusing
      on research gaps identified in the prior review. DATA SOURCES: MEDLINE (2004 to
      June 2012) and the Cochrane Library (through the second quarter of 2012). STUDY
      SELECTION: Randomized trials and observational studies that compared HIV
      screening strategies and reported clinical outcomes, evaluated the effects of
      starting ART at different CD4 cell count thresholds and long-term harms, or
      reported the effects of interventions on transmission risk. DATA EXTRACTION: 2
      authors abstracted and checked study details and quality using predefined
      criteria. DATA SYNTHESIS: No study directly evaluated the effects on clinical
      outcomes of screening versus no screening for HIV infection. A randomized trial
      and a subgroup analysis from a randomized trial found that ART initiation at CD4
      counts less than 0.250 * 109 cells/L was associated with a higher risk for death
      or AIDS-defining events than initiation at CD4 counts greater than 0.350 * 109
      cells/L (hazard ratios, 1.7 [95% CI, 1.1 to 2.5] and 5.3 [CI, 1.3 to 9.6]).
      Large, fair-quality cohort studies also consistently found that ART initiation at
      CD4 counts of 0.350 to 0.500 * 109 cells/L was associated with lower risk for
      death or AIDS-defining events than delayed initiation. New evidence from good
      quality cohorts with longer-term follow-up confirms a previously observed small
      increased risk for cardiovascular events associated with certain antiretrovirals.
      Strong evidence from 1 good-quality randomized trial and 7 observational studies
      found that ART was associated with a 10- to 20-fold reduction in risk for sexual
      transmission of HIV. LIMITATIONS: Only English-language articles were included.
      Observational studies were included. Studies done in resource-poor or high
      prevalence settings were included but might have limited applicability to general
      screening in the United States. CONCLUSION: Previous studies have shown that HIV
      screening is accurate, targeted screening misses a substantial proportion of
      cases, and treatments are effective in patients with advanced immunodeficiency.
      New evidence indicates that ART reduces risk for AIDS-defining events and death
      in persons with less advanced immunodeficiency and reduces sexual transmission of
      HIV. PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality.

PMID- 23165663
TI  - Screening for HIV in pregnant women: systematic review to update the 2005 U.S.
      Preventive Services Task Force recommendation.
AB  - BACKGROUND: A 2005 U.S. Preventive Services Task Force (USPSTF) review found good
      evidence that prenatal HIV screening is accurate and can lead to interventions
      that reduce the risk for mother-to-child transmission. PURPOSE: To update the
      2005 USPSTF review, focusing on previously identified research gaps and new
      evidence on treatments. DATA SOURCES: MEDLINE (2004 to June 2012) and the
      Cochrane Library (2005 to the second quarter of 2012). STUDY SELECTION:
      Randomized trials and cohort studies of pregnant women on risk for mother-to
      child transmission or harms associated with prenatal HIV screening or
      antiretroviral therapy during pregnancy. DATA EXTRACTION: 2 reviewers abstracted
      and confirmed study details and quality by using predefined criteria. DATA
      SYNTHESIS: No studies directly evaluated effects of prenatal HIV screening on
      risk for mother-to-child transmission or maternal or infant clinical outcomes.
      One fair-quality, large cohort study (HIV prevalence, 0.7%) found that rapid
      testing during labor was associated with a positive predictive value of 90%. New
      cohort studies of nonbreastfeeding women in the United States and Europe confirm
      that full-course combination antiretroviral therapy reduces rates of mother-to
      child transmission (<1% to 2.4% vs. 9% to 22% with no antiretroviral therapy).
      New cohort studies found antiretroviral therapy during pregnancy to be associated
      with increased risk for preterm delivery (<37 weeks' gestation); there were no
      clear associations with low birthweight, congenital abnormalities, or infant
      neurodevelopment. Evidence on long-term maternal harms after short-term
      antiretroviral therapy exposure during pregnancy remains sparse. LIMITATIONS:
      Only English-language articles were included. Studies conducted in resource-poor
      settings may be of limited applicability to screening in the United States.
      CONCLUSION: Antiretroviral therapy in combination with avoidance of breastfeeding
      and elective cesarean section in women with viremia reduces risk for mother-to
      child transmission. Use of certain antiretroviral therapy regimens during
      pregnancy may increase risk for preterm delivery. PRIMARY FUNDING SOURCE: Agency
      for Healthcare Research and Quality.

PMID- 23165664
TI  - Diagnosis of stable ischemic heart disease: summary of a clinical practice
      guideline from the American College of Physicians/American College of Cardiology
      Foundation/American Heart Association/American Association for Thoracic
      Surgery/Preventive Cardiovascular Nurses Association/Society of Thoracic
      Surgeons.
AB  - DESCRIPTION: The American College of Physicians (ACP) developed this guideline in
      collaboration with the American College of Cardiology Foundation (ACCF), American
      Heart Association (AHA), American Association for Thoracic Surgery, Preventive
      Cardiovascular Nurses Association, and Society of Thoracic Surgeons to help
      clinicians diagnose known or suspected stable ischemic heart disease. METHODS:
      Literature on this topic published before November 2011 was identified by using
      MEDLINE, Embase, Cochrane CENTRAL, PsychINFO, AMED, and SCOPUS. Searches were
      limited to human studies published in English. This guideline grades the evidence
      and recommendations according to a translation of the ACCF/AHA grading system
      into ACP's clinical practice guidelines grading system. RECOMMENDATIONS: This
      guideline includes 28 recommendations that address the following issues: the
      initial diagnosis of the patient who might have stable ischemic heart disease,
      cardiac stress testing to assess the risk for death or myocardial infarction in
      patients diagnosed with stable ischemic heart disease, and coronary angiography
      for risk assessment.

PMID- 23165665
TI  - Management of stable ischemic heart disease: summary of a clinical practice
      guideline from the American College of Physicians/American College of Cardiology
      Foundation/American Heart Association/American Association for Thoracic
      Surgery/Preventive Cardiovascular Nurses Association/Society of Thoracic
      Surgeons.
AB  - DESCRIPTION: The American College of Physicians (ACP) developed this guideline
      with the American College of Cardiology Foundation (ACCF), American Heart
      Association (AHA), American Association for Thoracic Surgery, Preventive
      Cardiovascular Nurses Association, and Society of Thoracic Surgeons to present
      the available evidence on the management of stable known or suspected ischemic
      heart disease. METHODS: Literature on this topic published before November 2011
      was identified by using MEDLINE, Embase, Cochrane CENTRAL, PsychINFO, AMED, and
      SCOPUS. Searches were limited to human studies published in English. This
      guideline grades the evidence and recommendations according to a translation of
      the ACCF/AHA grading system into ACP's clinical practice guidelines grading
      system. RECOMMENDATIONS: The guideline includes 48 specific recommendations that
      address the following issues: patient education, management of proven risk
      factors (dyslipidemia, hypertension, diabetes, physical activity body weight, and
      smoking), risk factor reduction strategies of unproven benefit, medical therapy
      to prevent myocardial infarction and death and to relieve symptoms, alternative
      therapy, revascularization to improve survival and symptoms, and patient follow
      up.

PMID- 23165667
TI  - Guidelines on diagnosis and treatment of stable ischemic heart disease: keeping
      up with a constantly evolving evidence base.

PMID- 23165668
TI  - Arise and judge the earth.

PMID- 23165669
TI  - Red blood cell transfusion.

PMID- 23165670
TI  - Improving the efficiency of advanced life support training.

PMID- 23165673
TI  - Sinus arrest from mad honey disease.

PMID- 23165674
TI  - Fatal laughter.

PMID- 23165675
TI  - Summary for patients. Effect of testosterone on response to sildenafil in men
      with erectile dysfunction.

PMID- 23165676
TI  - Summary for patients. Diagnosis of stable ischemic heart disease: recommendations
      from the American College of Physicians, American College of Cardiology
      Foundation, American Heart Association, American Association for Thoracic
      Surgery, Preventive Cardiovascular Nurses Association, and Society of Thoracic
      Surgeons.

PMID- 23165677
TI  - Summary for patients. Management of stable ischemic heart disease:
      recommendations from the American College of Physicians, American College of
      Cardiology Foundation, American Heart Association, American Association for
      Thoracic Surgery, Preventive Cardiovascular Nurses Association, and Society of
      Thoracic Surgeons.

PMID- 23165678
TI  - ACP Journal Club. Review: ACE inhibitors reduce risk for pneumonia.

PMID- 23165679
TI  - ACP Journal Club. Preexposure prophylaxis reduced HIV-1 spread in serodiscordant
      heterosexual couples.

PMID- 23165680
TI  - ACP Journal Club. Review: statins decrease mortality and major CV events in
      adults with CKD not receiving dialysis.

PMID- 23165682
TI  - ACP Journal Club. Review: intensive glucose control reduces surrogate, but not
      clinical, renal outcomes in type 2 diabetes.

PMID- 23165681
TI  - ACP Journal Club. Review: lipid-lowering drugs decrease all-cause and cardiac
      mortality and CV events in CKD.

PMID- 23165684
TI  - ACP Journal Club. Review: femoral and subclavian or internal jugular venous
      catheters do not differ for bloodstream infections.

PMID- 23165683
TI  - ACP Journal Club. rt-PA within 6 hours of acute ischemic stroke did not improve
      clinical outcomes at 6 months.

PMID- 23165685
TI  - ACP Journal Club. Fractional flow reserve-guided PCI reduced urgent
      revascularization at 7 months in coronary artery disease.

PMID- 23165686
TI  - ACP Journal Club. A single FIT (>= 50 ng Hb/mL) detected 38% of screen-detected
      advanced colorectal neoplasia.

PMID- 23165687
TI  - ACP Journal Club. Refusal of transfusions for cardiac surgery was not associated
      with shorter long-term survival.

PMID- 23165688
TI  - CKD-EPI eGFR categories were better than MDRD categories for predicting mortality
      in a range of populations.

PMID- 23165689
TI  - An 8-factor prognostic model predicted early death in patients with traumatic
      bleeding.
AB  - QUESTION: Does a prognostic model accurately estimate risk for early death in
      patients with traumatic bleeding? METHODS:  DESIGN: 2 cohort studies: Clinical
      Randomisation of an Antifibrinolytic in Significant Haemorrhage (CRASH-2) trial
      (derivation) and Trauma Audit and Research Network (TARN) dataset (validation).
      SETTING: 274 hospitals in 40 countries (derivation cohort) and 60% of hospitals
      that received trauma patients in England and Wales and some hospitals in Europe
      (validation cohort). PATIENTS: Derivation cohort: 20 127 trauma patients with, or
      at risk for, significant bleeding within 8 hours of injury (median age 30 y,
      median 2 h from injury). Validation cohort: 14 220 patients > 15 years of age
      (median age 39 y, median 1 h from injury) who arrived at hospital alive and had
      >= 1 of death from injury during admission, hospitalization > 3 days, need for
      intensive or high-dependency care, or need for interhospital transfer for
      specialist care. Patients who had isolated closed limb injuries or were > 65
      years of age with isolated fractured neck of femur or pubic ramus fracture were
      excluded. DESCRIPTION OF PREDICTION GUIDE: The prognostic model included country
      (low, middle, or high income), age, time since injury, Glasgow coma score,
      systolic blood pressure, respiratory rate, heart rate, and type of injury (blunt
      or penetrating) (available at www.crash2.lshtm.ac.uk). OUTCOME: Early death (in
      hospital death within 4 wk of injury). MAIN RESULTS: 15% and 12% of patients from
      the derivation and validation cohorts died. The operating characteristics of the
      model in the derivation and validation cohorts are in the Table. CONCLUSION: An 8
      factor prognostic model predicted early death in patients with traumatic
      bleeding.

PMID- 23165690
TI  - Single-nucleotide polymorphisms reveal patterns of allele sharing across the
      species boundary between rhesus (Macaca mulatta) and cynomolgus (M. fascicularis)
      macaques.
AB  - Both phenotypic and genetic evidence for asymmetric hybridization between rhesus
      (Macaca mulatta) and cynomolgus (Macaca fascicularis) macaques has been observed
      in the region of Indochina where both species are sympatric. The large-scale
      sharing of major histocompatibility complex (MHC) class II alleles between the
      two species in this region supports the hypothesis that genes, and especially
      genes involved in immune response, are being transferred across the species
      boundary. This differential introgression has important implications for the
      incorporation of cynomolgus macaques of unknown geographic origin in biomedical
      research protocols. Our study found that for 2,808 single-nucleotide polymorphism
      (SNP) markers, the minor allele frequencies (MAF) and observed heterozygosity
      calculated from a sample of Vietnamese cynomolgus macaques was significantly
      different from those calculated from samples of both Chinese rhesus and
      Indonesian cynomolgus macaques. SNP alleles from Chinese rhesus macaques were
      overrepresented in a sample of Vietnamese cynomolgus macaques relative to their
      Indonesian conspecifics and located in genes functionally related to the primary
      immune system. These results suggest that Indochinese cynomolgus macaques
      represent a genetically and immunologically distinct entity from Indonesian
      cynomolgus macaques.

PMID- 23165692
TI  - Light-harvesting ytterbium(III)-porphyrinate-BODIPY conjugates: synthesis,
      excitation-energy transfer, and two-photon-induced near-infrared-emission
      studies.
AB  - Based on a donor-acceptor framework, several conjugates have been designed and
      prepared in which an electron-donor moiety, ytterbium(III) porphyrinate (YbPor),
      was linked through an ethynyl bridge to an electron-acceptor moiety, boron
      dipyrromethene (BODIPY). Photoluminescence studies demonstrated efficient energy
      transfer from the BODIPY moiety to the YbPor counterpart. When conjugated with
      the YbPor moiety, the BODIPY moiety served as an antenna to harvest the lower
      energy visible light, subsequently transferring its energy to the YbPor
      counterpart, and, consequently, sensitizing the Yb(III) emission in the near
      infrared (NIR) region with a quantum efficiency of up to 0.73% and a lifetime of
      around 40 MUs. Moreover, these conjugates exhibited large two-photon-absorption
      cross-sections that ranged from 1048-2226 GM and strong two-photon-induced NIR
      emission.

PMID- 23165693
TI  - Copper(II) catalysis of water oxidation.
AB  - Copper leads to a breakup: simple Cu(II) salts are shown to be highly reactive as
      water oxidation electrocatalysts in neutral to weakly basic aqueous buffer
      solutions of CO(2)/HCO(3)(-)/CO(3)(2-) or HPO(4)(2-)/PO(4)(3-). Coordination to
      the buffer anions under these conditions prevents the precipitation of Cu(OH)(2),
      CuCO(3), or Cu(3)(PO(4))(2) and appears to stabilize higher oxidation states of
      copper.

PMID- 23165694
TI  - A {Cr2Dy4} compressed octahedron: the first sulfate-based single-molecule magnet.
AB  - A unique compressed octahedral {Cr(III)(2)Dy(III)(4)} aggregate is the first
      sulfate-based single-molecule magnet (SMM) with U(eff)/k(B) = 39.7 K and tau(0) =
      2.9 * 10(-9) s. Its synthesis opens a new avenue to prepare 3d-4f coordination
      clusters.

PMID- 23165695
TI  - Secondary chronic cluster headache treated by posterior hypothalamic deep brain
      stimulation: first reported case.
AB  - INTRODUCTION: Deep brain stimulation (DBS) of the posterior hypothalamus (pHyp)
      has been reported as an effective treatment for primary, drug-refractory and
      chronic cluster headache (CCH). We here describe the use of such a procedure for
      the treatment of secondary CCH due to a neoplasm affecting the soft tissues of
      the right hemiface. METHODS: A 27-year-old man affected by infiltrating
      angiomyolipoma of the right hemiface who subsequently developed drug refractory
      homolateral CCH underwent DBS of the right pHyp region at the Fondazione IRCCS
      Istituto Nazionale Neurologico Carlo Besta. RESULTS: After surgery, the patient
      presented a significant reduction in frequency of pain bouts. However, because of
      a subsequent infection, the entire system was removed. After re-implantation of
      the system, successful outcome was observed at 2 years follow-up. DISCUSSION:
      This brief report shows the feasibility of pHyp DBS in secondary drug-refractory
      CCH syndromes; future reports are needed in order to confirm our positive result.

PMID- 23165696
TI  - Randomized, double-blind, placebo-controlled, phase II trial of gabapentin
      enacarbil for migraine prophylaxis.
AB  - OBJECTIVE: The objective of this article is to evaluate the efficacy and safety
      of gabapentin enacarbil (GEn) for migraine prophylaxis. METHODS: In this
      randomized, double-blind, parallel-group study, patients with International
      Headache Society-defined migraine who met criteria suggesting the need for
      prophylactic therapy were randomized 2:1:2:2:1 to one of the following five
      groups, designated according to target daily dose of study medication during the
      20-week treatment period: placebo, GEn 1200 mg, GEn 1800 mg, GEn 2400 mg, or GEn
      3000 mg. RESULTS: The intent-to-treat population included 523 patients (n = 128
      placebo, n = 66 GEn 1200 mg, n = 134 GEn 1800 mg, n = 133 GEn 2400 mg, n = 62 GEn
      3000 mg). No statistically significant difference between active treatment (the
      average of 1800 mg and 2400 mg treatment groups) and placebo was found for change
      from baseline in the number of migraine headache days during the last four weeks
      of treatment prior to taper (the primary endpoint). Results of analyses of the
      primary endpoint using the per protocol population, analyses using imputation
      methods different from those of the primary analysis, and nonparametric analyses
      were consistent with the primary analysis in showing no difference between active
      treatment and placebo. The pattern of results was similar for the secondary
      efficacy endpoints. Pharmacokinetic data demonstrate that patients had adequate
      estimated exposure to GEn. The adverse event profile of GEn was consistent with
      that in previous studies. CONCLUSION: GEn did not significantly differ from
      placebo for migraine headache prophylaxis. A high placebo effect should be
      considered when interpreting these results.

PMID- 23165697
TI  - Effect of geometrical structure on the in vivo quality change of a three
      dimensionally perforated porous bone cell scaffold made of apatite/collagen
      composite.
AB  - Biodegradable artificial bone blocks with interconnective pores were prepared
      using a self-setting apatite/collagen composite cement as a cell scaffold for
      bone regenerative medicine. The biological behavior of the blocks was tested in
      rats, and the change in their properties after implantation was measured. One
      cubic block [10 mm X 10 mm X 10 mm; porous composite (PC)] was obtained from
      apatite cement (apatite/collagen cement; 80% of apatite:20% of collagen) with 60
      interconnecting holes, 500 um in diameter. The other blocks (NC and NN) without
      holes were obtained from the apatite/collagen and plain apatite cements,
      respectively. All blocks were implanted in the rats for 56 days. Changes in the
      amount and density (block mineral mass and block mineral density) of the blocks
      were evaluated based on dual energy X-ray absorptiometry images, and the order of
      biodegradation was PC < NC < NN. After implantation, the blocks were removed, and
      subjected to an X-ray diffraction (XRD) analysis, Fourier-transformed infrared
      (FT-IR) spectroscopy and thermogravimetry (TG). The XRD peaks of all blocks
      increased significantly. TG revealed that the amount of carbonated apatite also
      increased with time. However, the organic component of PC depended on the
      implantation period, consistent with the FT-IR results. Because PC had
      interconnective macro- and micropores in the apatite/collagen matrices, the
      results indicated that soft tissue penetrated the block carbonated apatite was
      generated, bone remodeling was accelerated in the implant.

PMID- 23165698
TI  - Linked in: ASCO, NCI tap health information technology to improve cancer
      prevention, care, and research.

PMID- 23165699
TI  - Strides in personalized medicine.

PMID- 23165700
TI  - Cutaneous myeloid sarcoma: natural history and biology of an uncommon
      manifestation of acute myeloid leukemia.
AB  - We conducted a retrospective study of patients with cutaneous myeloid sarcoma,
      from 2 tertiary care institutions. Eighty-three patients presented, with a mean
      age of 52 years. Diagnosis of myeloid sarcoma in the skin was difficult due to
      the low frequency of myeloperoxidase and/or CD34+ cases (56% and 19% of tested
      cases, respectively). Seventy-one of the 83 patients (86%) had >= 1 bone marrow
      biopsy. Twenty-eight (39%) had acute myeloid leukemia with monocytic
      differentiation. Twenty-three had other de novo acute myeloid leukemia subtypes.
      Thirteen patients had other myeloid neoplasms, of which 4 ultimately progressed
      to an acute myeloid leukemia. Seven had no bone marrow malignancy. Ninety-eight
      percent of the patients received chemotherapy, and approximately 89% died of
      causes related to their disease. Cutaneous myeloid sarcoma in most cases
      represents an aggressive manifestation of acute myeloid leukemia. Diagnosis can
      be challenging due to lack of myeloblast-associated antigen expression in many
      cases, and difficulty in distinguishing monocyte-lineage blasts from neoplastic
      and non-neoplastic mature monocytes.

PMID- 23165701
TI  - [Brown tumor of the maxilla].

PMID- 23165702
TI  - [Short-term sentence memory in children with auditory processing disorders].
AB  - BACKGROUND: Based on the study of Nickisch et al. [1] the 4 discriminatory
      variables of second-year elementary school-age children with and without APD
      should now be investigated with respect to the variable "sentence memory".
      MATERIAL AND METHODS: Retrospective analysis. Sentence memory was tested via the
      subtest "IS" of the Heidelberger Sprachentwicklungstest [2]. All children were
      examined with the 4 APD-tests (see results) and the subtest "IS". PARTICIPANTS:
      n=24 with monosymptomatic APD; n=21 with APD + Specific Language Impairment
      [SLI]; n=48 controls [developmentally normal]. RESULTS: Mean sentence memory
      achievement of the clinical groups differed statistically from the control group
      (p<0.001). The comparison of mean values in the 4 discriminatory variables in
      each case revealed distinctly significant differences (p<0.001) in favour of the
      control group (word-comprehension in background noise; dichotic word listening;
      phonological digit span; nonword repetition). Children with APD, by contrast, did
      not statistically differ in any meaningful in their mean achievement from those
      with APD + SLI. Between the mean value of the clinical groups and the control
      group effect sizes d were calculated. The effects were not only statistically
      significant but also of clinical and practical relevance given that the CI was
      small. CONCLUSION: High mean value differences in sentence memory as well as in
      nonword repetition in children with APD as in those with APD + SLI to normally
      typically developed control children shed new light on questions regarding a
      fluent transition between APD and SLI or a comorbid appearance.

PMID- 23165703
TI  - [The role of CT in the diagnosis of peritonsillar abscesses after Punctio Sicca].
AB  - BACKGROUND: Peritonsillar abscesses are considered to be complications of a
      peritonsillar inflammation and are a frequently occurring condition. Often, to
      confirm the presence of an abscess and to locate it following a dry-tap aspirate,
      computed tomography (CT) is performed. No validated data has been published to
      date concerning the role of CT in the diagnosis of peritonsillar abscesses.
      MATERIAL AND METHODS: In a retrospective analysis, the records of patients
      presenting at a German university hospital with a suspected peritonsillar abscess
      between 2006 and 2011 were evaluated. A particular focus was placed on the
      diagnostic procedure for patients with dry tap. The CT images were evaluated by 2
      neuroradiologists. RESULTS: 310 patients with a suspected peritonsillar abscess
      from the period 2006-2011 were evaluated. In 51 cases (31 male and 20 female
      patients; 16.5 %), a dry tap was found to have occurred. Of these, in 42 patients
      (82.3 %) a CT scan was performed to rule out or locate an abscess. In 36 patients
      (85.7 %), an abscess was verified by CT imaging. CONCLUSION: Where there are
      clinical grounds for suspecting a peritonsillar abscess, and where a dry tap
      occurs, our data indicate that performing a CT scan to verify and locate an
      abscess is an effective diagnostic procedure. However, greater attention should
      be paid to additional diagnostic methods.

PMID- 23165706
TI  - Commentary on community-led total sanitation and human rights: should the right
      to community-wide health be won at the cost of individual rights?
AB  - The Millennium Development Goals (MDGs) set out to halve the proportion of the
      population without access to basic sanitation between 1990 and 2015. The slow
      pace of progress has lead to a search for innovative responses, including social
      motivation approaches. One example of this type of approach is 'Community-led
      Total Sanitation' (CLTS). CLTS represents a major shift for sanitation projects
      and programmes in recognising the value of stopping open-defecation across the
      whole community, even when the individual toilets built are not necessarily
      wholly hygienic. However, recent publications on CLTS document a number of
      examples of practices which fail to meet basic ethical criteria and infringe
      human rights. There is a general theme in the CLTS literature encouraging the use
      of 'shame' or 'social stigma' as a tool for promoting behaviours. There are
      reported cases where monetary benefits to which individuals are otherwise
      entitled or the means to practice a livelihood are withheld to create pressures
      to conform. At the very extreme end of the scale, the investigation and
      punishment of violence has reportedly been denied if the crime occurred while
      defecating in the open, violating rights to a remedy and related access to
      justice. While social mobilisation in general, and CLTS in particular, have
      drastically and positively changed the way we think about sanitation, they
      neither need nor benefit from an association with any infringements of human
      rights.

PMID- 23165705
TI  - Sinomenine hydrochloride inhibits human hepatocellular carcinoma cell growth in
      vitro and in vivo: involvement of cell cycle arrest and apoptosis induction.
AB  - Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide.
      However, therapies against HCC to date have not been completely effective.
      Sinomenine hydrochloride (SH), an anti-arthritis drug applied in clinical
      practice, has been reported to have in vitro anti-neoplastic activity in various
      cancer cells. Whether SH inhibits HCC remains unknown. For this purpose, in this
      study, MTT assay was used to determine cell growth. Flow cytometry, Hoechst
      staining, DNA fragmentation, western blot analysis, immunohistochemisty and TUNEL
      staining were performed to investigate the mechanisms involved. The in vivo
      activity of SH was determined using a mouse xenograft model. SH inhibited the
      growth of various types of human HCC cells in vitro. We found that SH promoted
      cell cycle arrest in the G1 phase and sub-G1 formation, associated with the
      increased p21/WAF1/Cip1 expression. Additionally, SH induced caspase-dependent
      apoptosis, which involved the disruption of mitochondrial membrane potential, the
      increased release of cytochrome c and Omi/HtrA2 from the mitochondria into the
      cytoplasm, the downregulation of Bcl-2 and the upregulation of Bax, the
      activation of a caspase cascade (caspase-8, -10, -9 and -3) and PARP, as well as
      the decreased expression of survivin. The SH-suppressed growth of human HCC
      xenografts in vivo occurred due to the decrease in proliferation and the
      induction of apoptosis, implicating the activation of caspase-3, the upregulation
      of p21 and the downregulation of survivin. These findings suggest that SH
      exhibits anticancer efficacy in vitro and in vivo involving cell cycle and
      caspase-dependent apoptosis and may serve as a potential drug candidate against
      HCC.

PMID- 23165704
TI  - Human pericytes for ischemic heart repair.
AB  - Human microvascular pericytes (CD146(+)/34(-)/45(-)/56(-)) contain multipotent
      precursors and repair/regenerate defective tissues, notably skeletal muscle.
      However, their ability to repair the ischemic heart remains unknown. We
      investigated the therapeutic potential of human pericytes, purified from skeletal
      muscle, for treating ischemic heart disease and mediating associated repair
      mechanisms in mice. Echocardiography revealed that pericyte transplantation
      attenuated left ventricular dilatation and significantly improved cardiac
      contractility, superior to CD56+ myogenic progenitor transplantation, in acutely
      infarcted mouse hearts. Pericyte treatment substantially reduced myocardial
      fibrosis and significantly diminished infiltration of host inflammatory cells at
      the infarct site. Hypoxic pericyte-conditioned medium suppressed murine
      fibroblast proliferation and inhibited macrophage proliferation in vitro. High
      expression by pericytes of immunoregulatory molecules, including interleukin-6,
      leukemia inhibitory factor, cyclooxygenase-2, and heme oxygenase-1, was sustained
      under hypoxia, except for monocyte chemotactic protein-1. Host angiogenesis was
      significantly increased. Pericytes supported microvascular structures in vivo and
      formed capillary-like networks with/without endothelial cells in three
      dimensional cocultures. Under hypoxia, pericytes dramatically increased
      expression of vascular endothelial growth factor-A, platelet-derived growth
      factor-beta, transforming growth factor-beta1 and corresponding receptors while
      expression of basic fibroblast growth factor, hepatocyte growth factor, epidermal
      growth factor, and angiopoietin-1 was repressed. The capacity of pericytes to
      differentiate into and/or fuse with cardiac cells was revealed by green
      fluorescence protein labeling, although to a minor extent. In conclusion,
      intramyocardial transplantation of purified human pericytes promotes functional
      and structural recovery, attributable to multiple mechanisms involving paracrine
      effects and cellular interactions.

PMID- 23165707
TI  - Solar inactivation of four Salmonella serovars in fresh and marine waters.
AB  - Sunlight-mediated disinfection of water is of interest to both the drinking and
      recreational water quality community of researchers due to its potential to
      reduce microbial contamination and waterborne illness. Photo-inactivation of
      enteric bacteria has primarily been investigated using Escherichia coli and
      laboratory strains of model bacteria. The present study sought to document the
      photo-inactivation of environmental isolates of Salmonella in filter-sterilized
      natural seawater and freshwater and to test the hypothesis that diverse
      Salmonella serovars decay at similar rates both within and between water
      matrices. The inactivation of Salmonella enterica Typhimurium LT2, Typhimurium
      ST19, Heidelberg, and Mbandaka was examined in sunlit and dark microcosms. First
      order decay was observed in sunlit microcosms; the time until 90% inactivation
      was of the order of 10 min. A significant shoulder, of the order of 1 hr in
      length, was observed in the freshwater microcosms during which concentrations
      were stable. Serovar Mdandaka decayed more slowly than other serovars in both
      seawater and freshwater. The serovars were extremely stable in the dark
      microcosms showing little to no decay over 53 days. The results document intra
      species variation in photo-inactivation, likely owing to differences in
      intracellular concentrations of photo-sensitizing molecules or molecules that
      quench reactive species.

PMID- 23165708
TI  - Research considerations for more effective groundwater monitoring.
AB  - Since numerous pathogens occur in feces, water is monitored for fecal
      contamination using indicator organisms rather than individual pathogens.
      Although this approach is supported by health effects data in recreational
      waters, it is questionable when used for drinking water. Most outbreaks in
      groundwater occur in systems that have not violated the US EPA's maximum
      contaminant limit (MCL) for total coliforms within 12 months before the outbreak.
      Additionally, environmentally stable viruses and parasites are often detected in
      drinking water samples with no detectable indicators. Recent detections of
      Escherichia coli O157:H7 and Campylobacter jejuni in groundwaters in the apparent
      absence of indicators also cast some doubt on the worth of indicators for fecal
      bacterial pathogens. Individual pathogen monitoring is now technically achievable
      but currently unreasonable due to the number of possible pathogens and the costs
      involved. Several alternatives to pathogen monitoring could significantly reduce
      the frequency at which pathogens occur in waters testing negative for indicators:
      (i) increasing sample volumes for indicators, (ii) increasing monitoring
      frequency, (iii) using a suite of indicators, (iv) using a more conservative
      polymerase chain reaction (PCR) method, (v) sampling when fecal contamination is
      most likely present or (vi) any combination of these options.

PMID- 23165709
TI  - Proapoptotic effect of a micropollutant (tris-(2-chloroethyl)-phosphate) at
      environmental level in primary cultured renal proximal tubule cells.
AB  - Being a typical micropollutant, tris-(2-chloroethyl)-phosphate (TCEP) is often
      found in aquatic environments. However, the potential effects of TCEP at
      environmental concentrations on apoptotic mechanisms are mostly unknown. Thus,
      the purpose of this study is to investigate the apoptotic regulatory protein
      expression of TCEP at environmental concentration in primary cultured renal
      proximal tubule cells (PTCs). The results show that TCEP at 0.01 and 1 mg L(-1)
      significantly increased the phosphorylation of c-Jun-NH2-terminal kinase (JNK)
      (135.5 and 138.0% of the control, respectively), and significantly decreased the
      expression of Bcl-2 and cIAP-2 at all tested concentrations, except for a slight
      decrease of Bcl-2 at 0.01 mg L(-1). In addition, TCEP significantly increased the
      expression of caspase-3 at all three concentrations (132.6, 172.6 and 167.9% of
      the control, respectively) and caspase-9 at 1 and 10 mg L(-1) (128.3 and 144.5%
      of the control, respectively). Furthermore, TCEP increased the apoptotic cell
      population in a flow cytometry analysis. In conclusion, environmental TCEP might
      have a dose-dependent proapoptotic effect with a decrease of DNA synthesis and
      cell number in primary cultured renal PTCs.

PMID- 23165710
TI  - The efficacy of simulated solar disinfection (SODIS) against coxsackievirus,
      poliovirus and hepatitis A virus.
AB  - The antimicrobial activity of simulated solar disinfection (SODIS) against
      enteric waterborne viruses including coxsackievirus-B5, poliovirus-2 and
      hepatitis A virus was investigated in this study. Assays were conducted in
      transparent 12-well polystyrene microtitre plates containing the appropriate
      viral test suspension. Plates were exposed to simulated sunlight at an optical
      irradiance of 550 Wm(-2) (watts per square metre) delivered from a SUNTESTTM CPS+
      solar simulator for 6 hours. Aliquots of the viral test suspensions were taken at
      set time points and the level of inactivation of the viruses was determined by
      either culture on a HeLa cell monolayer for coxsackievirus-B5 and poliovirus-2 or
      by utilising a chromogenic antibody-based approach for hepatitis A virus. With
      coxsackievirus-B5, poliovirus-2 and hepatitis A virus, exposure to SODIS at an
      optical irradiance of 550 Wm(-2) for 1-2 hours resulted in complete inactivation
      of each virus. The findings from this study suggest that under appropriate
      conditions SODIS may be an effective technique for the inactivation of enteric
      viruses in drinking water. However, further verification studies need to be
      performed using natural sunlight in the region where the SODIS technology is to
      be employed to validate our results.

PMID- 23165711
TI  - Direct and indirect QMRA of infectious Cryptosporidium oocysts in reclaimed
      water.
AB  - Water scarcity leads to an increased use of reclaimed water, which in turn calls
      for an improvement in water reclamation procedures to ensure adequate quality of
      the final effluent. The presence of infectious Cryptosporidium oocysts (IOO) in
      reclaimed water is a health hazard for users of this resource. Here, we gathered
      information on Cryptosporidium (concentrations, infectivity and genotype) in
      order to perform quantitative microbial risk assessment (QMRA). Moreover, data
      concerning the spores of sulphite-reducing clostridia (SRC) were used to
      undertake QMRA at a screening level. Our results show that the probability of
      infection (PI) by Cryptosporidium depends on the tertiary treatment type. The
      mean PI using the exponential dose-response model was 3.69 * 10(-6) in tertiary
      effluents (TE) treated with UV light, whereas it was 3 log(10) units higher, 1.89
      * 10(-3), in TE not treated with this disinfection method. With the beta-Poisson
      model, the mean PI was 1.56 * 10(-4) in UV-treated TE and 2 log(10) units higher,
      4.37 * 10(-2), in TE not treated with UV. The use of SRC to perform QMRA of
      Cryptosporidium showed higher PI than when using directly IOO data. This
      observation suggests the former technique is a conservative method of QMRA.

PMID- 23165712
TI  - Removal and relationships of microbial indicators in a water treatment and
      reclamation facility.
AB  - A wastewater treatment and reclamation facility in north-east Spain was monitored
      over 1 year to determine the occurrence and concentrations of different microbial
      indicators (Escherichia coli, fecal enterococci, somatic bacteriophages and
      spores of sulfite-reducing clostridia). The removal of the indicators and its
      relationships through the wastewater treatment and reclamation trains were
      evaluated. The results obtained show that the reclamation treatments evaluated
      present a different efficiency in indicator microorganisms' removal depending on
      the type of microorganism. The E. coli and enterococci present an average
      reduction slightly higher than the other indicators, followed by somatic
      bacteriophages and spores of sulfite-reducing clostridia. The Spearman's
      correlations indicate that it is not suitable to use any of the bacterial
      indicators evaluated to predict the content of virus or spores of sulfite
      reducing clostridia. Therefore, in order to evaluate the microbiological risk of
      the reclaimed effluent use, it is necessary to monitor the three types of
      indicator microorganisms (bacteria, virus and protozoa).

PMID- 23165713
TI  - The synergistic effect of Escherichia coli inactivation by sequential
      disinfection with low level chlorine dioxide followed by free chlorine.
AB  - To the best of our knowledge, there was little information available on pathogen
      removal using low level disinfectant followed by free chlorine in sequential
      disinfection (SD). This study investigated Escherichia coli inactivation by four
      types of disinfection: single step disinfection (SSD), SD, traditional sequential
      disinfection (TSD) and mixed disinfectant disinfection (MDD). Results indicated
      that SD had higher ability to inactivate E. coli than the others, indicating
      there was a positive synergistic effect on chlorine disinfection by prior dosing
      with a low level of chlorine dioxide (ClO(2)). The ONPG assay suggested that the
      permeability of cell wall rather than the viability of E. coli were changed under
      0.02 mg/l ClO(2) treatment. The coexistence of residual ClO(2) and free chlorine
      also plays an active synergistic effect. Additionally, temperature had a positive
      effect on E. coli inactivation in SD, while inactivation was reduced in alkaline
      compared to neutral and acidic conditions.

PMID- 23165714
TI  - Unsealed tubewells lead to increased fecal contamination of drinking water.
AB  - Bangladesh is underlain by shallow aquifers in which millions of drinking water
      wells are emplaced without annular seals. Fecal contamination has been widely
      detected in private tubewells. To evaluate the impact of well construction on
      microbial water quality 35 private tubewells (11 with intact cement platforms, 19
      without) and 17 monitoring wells (11 with the annulus sealed with cement, six
      unsealed) were monitored for culturable Escherichia coli over 18 months.
      Additionally, two 'snapshot' sampling events were performed on a subset of wells
      during late-dry and early-wet seasons, wherein the fecal indicator bacteria (FIB)
      E. coli, Bacteroidales and the pathogenicity genes eltA (enterotoxigenic E. coli;
      ETEC), ipaH (Shigella) and 40/41 hexon (adenovirus) were detected using
      quantitative polymerase chain reaction (qPCR). No difference in E. coli detection
      frequency was found between tubewells with and without platforms. Unsealed
      private wells, however, contained culturable E. coli more frequently and higher
      concentrations of FIB than sealed monitoring wells (p < 0.05), suggestive of
      rapid downward flow along unsealed annuli. As a group the pathogens ETEC,
      Shigella and adenovirus were detected more frequently (10/22) during the wet
      season than the dry season (2/20). This suggests proper sealing of private
      tubewell annuli may lead to substantial improvements in microbial drinking water
      quality.

PMID- 23165715
TI  - Seasonal variations in the risk of gastrointestinal illness on a tropical
      recreational beach.
AB  - The objectives of this study were to examine the seasonal changes in the risk of
      gastrointestinal (GI) illness of beachgoers in the tropics, to compare the
      association between GI illness and water quality using various indicator
      organisms, and to study other beach health hazards. A prospective cohort study
      during two seasonal periods (summer and autumn) was conducted in a beach
      surrounded by intensive residential development. Analyses demonstrated that
      although densities of indicators were well below water quality standards
      throughout the study, they were significantly higher during the autumn season.
      The incidence of GI illness among beachgoers was also higher during the rainy
      season. A higher incidence of GI illness was observed for bathers during the
      autumn season when compared to non-bathers, while a somewhat lower incidence was
      observed during the summer. This study showed that rainfall contributes to higher
      levels of microbial contaminants and GI risk to beachgoers. The association
      between GI illness and Enterococcus using culture counts showed the highest odds
      ratio among all indicator parameters including those using molecular methods. A
      much higher risk of GI illness among children under 5 years was observed among
      all beachgoers.

PMID- 23165716
TI  - Enumeration of viable and non-viable larvated Ascaris eggs with quantitative PCR.
AB  - The goal of this study was to further develop an incubation-quantitative
      polymerase chain reaction (qPCR) method for quantifying viable Ascaris eggs by
      characterizing the detection limit and number of template copies per egg,
      determining the specificity of the method, and testing the method with viable and
      inactivated larvated eggs. The number of template copies per cell was determined
      by amplifying DNA from known numbers of eggs at different development stages; the
      value was estimated to be 32 copies. The specificity of the method was tested
      against a panel of bacteria, fungi, protozoa and helminths, and no amplification
      was found with non-target DNA. Finally, fully larvated eggs were inactivated by
      four different treatments: 254 nm ultraviolet light, 2,000 ppm NH(3)-N at pH 9,
      moderate heat (48  degrees C) and high heat (70  degrees C). Concentrations of
      treated eggs were measured by direct microscopy and incubation-qPCR. The qPCR
      signal decreased following all four treatments, and was in general agreement with
      the decrease in viable eggs determined by microscopy. The incubation-qPCR method
      for enumerating viable Ascaris eggs is a promising approach that can produce
      results faster than direct microscopy, and may have benefits for applications
      such as assessing biosolids.

PMID- 23165717
TI  - Synergistic effect of heat and solar UV on DNA damage and water disinfection of
      E. coli and bacteriophage MS2.
AB  - The response of a representative virus and indicator bacteria to heating, solar
      irradiation, or their combination, was investigated in a controlled solar
      simulator and under real sun conditions. Heating showed higher inactivation of
      Escherichia coli compared to the bacteriophage MS2. Heating combined with natural
      or simulated solar irradiation demonstrated a synergistic effect on the
      inactivation of E. coli, with up to 3-log difference for 50  degrees C and
      natural sun insolation of 2,000 kJ m(-2) (compared to the sum of the separate
      treatments). Similar synergistic effect was also evident when solar-UV induced
      DNA damage to E. coli was assessed using the endonuclease sensitive site assay
      (ESS). MS2 was found to be highly resistant to irradiation and heat, with a
      slightly synergistic effect observed only at 59  degrees C and natural sun
      insolation of 5,580 kJ m(-2). Heat treatment also hindered light-dependent
      recovery of E. coli making the treatment much more effective.

PMID- 23165718
TI  - The effect of poultry manure application rate and AlCl(3) treatment on bacterial
      fecal indicators in runoff.
AB  - Increasing costs associated with inorganic fertilizer have led to widespread use
      of broiler litter. Proper land application, typically limiting nutrient loss, is
      essential to protect surface water. This study was designed to evaluate litter
      borne microbial runoff (heterotrophic plate count bacteria, staphylococci,
      Escherichia coli, enterococci, and Clostridium perfringens) while applying
      typical nutrient-control methods. Field studies were conducted in which plots
      with high and low litter rates, inorganic fertilizer, AlCl(3)-treated litter, and
      controls were rained on five times using a rain generator. Overall, microbial
      runoff from poultry litter applied plots was consistently greater (2-5 log(10)
      plot(-1)) than controls. No appreciable effect on microbial runoff was noted from
      variable litter application rate or AlCl(3) treatments, though rain event, not
      time, significantly affected runoff load. C. perfringens and staphylococci runoff
      were consistently associated with poultry litter application, during early rain
      events, while other indicators were unreliable. Large microbial runoff pulses
      were observed, ranging from 10(2) to 10(10) CFU plot(-1); however, only a small
      fraction of litter-borne microbes were recoverable in runoff. This study
      indicated that microbial runoff from litter-applied plots can be substantial, and
      that methods intended to reduce nutrient losses do not necessarily reduce
      microbial runoff.

PMID- 23165719
TI  - Characteristics of small residential and commercial water systems that influence
      their likelihood of being on drinking water advisories in rural British Columbia,
      Canada: a cross-sectional study using administrative data.
AB  - Health officials often lack information about characteristics that predict which
      water systems are most likely to be placed on and to persist on drinking water
      advisories (e.g. health warnings offering advice or information). This study uses
      data collected by the Interior Health Authority in British Columbia to
      characterize water systems on advisory for microbiological threats and to
      identify the variables associated with advisory status and length. By
      systematically extracting key characteristics, this study explores advisory
      status by examining associated variables: water systems size, administrative
      area, governance structure, water source, treatment level, and service type (e.g.
      residential or commercial systems). Results show residential and commercial water
      systems have different characteristics associated with advisory status and
      length. For residential systems, certain governance structures are more likely to
      be placed on and to stay on advisory, especially the cooperative governance
      structures not operated by local governments. For commercial systems,
      administrative area and system size were associated with advisory status, but not
      advisory length. The overall results highlight the influence of governance
      structure and support the need for targeted interventions to improve residential
      small water systems not operated by local governments or utilities. Lastly, these
      results show how health officials can use administrative data for program
      planning and evaluation.

PMID- 23165720
TI  - Thermotolerant Acanthamoeba spp. isolated from therapeutic hot springs in
      Northwestern Iran.
AB  - This study was conducted to address the distribution of Acanthamoeba genotypes in
      therapeutic hot springs in Iran. Sixty water and sediment samples were collected
      from bicarbonate, sulphur, and sodium chloride thermal springs in the northwest.
      All hot springs examined are used mainly for health purposes in Iran.
      Acanthamoeba were identified by both morphology and PCR (polymerase chain
      reaction). Genotype identification was based on the sequencing of a highly
      variable and informative region of Diagnostic Fragment 3 (stem 29-1 of 18S rRNA
      gene) within Acanthamoeba-specific amplimer (ASA.S1). Twenty percent of hot
      springs were contaminated with thermotolerant Acanthamoeba belonging to the
      potentially pathogenic T4 and T3 genotypes. A high number (91.7%) of strains
      showed growth at 37  degrees C, and eight isolates showed growth at 42  degrees
      C. A single isolate (HSNW2) was detected in waters at 70  degrees C. The presence
      of thermotolerant Acanthamoeba highlights a risk factor for susceptible
      individuals, as Acanthamoeba-related keratitis continues to rise in Iran.
      Periodic surveillance of thermal waters as well as improved filtration and
      disinfection is recommended to prevent disease related to pathogenic
      Acanthamoeba. This is the first comprehensive molecular study of Acanthamoeba
      genotypes in hot springs in Iran and the first to report the occurrence of the T3
      genotype (corresponding to Acanthamoeba griffini) in thermal water sources in
      this country.

PMID- 23165721
TI  - Analysis and retention behavior of isoflavone glycosides and aglycones in Radix
      Astragali by HPLC with hydroxypropyl-beta-cyclodextrin as a mobile phase
      additive.
AB  - In order to determine isoflavone glycosides (calycosin-7-O-beta-D-glucoside and
      formononetin-7-O-beta-D-glucoside) and aglycones (calycosin and formononetin), a
      simple HPLC method with isocratic elution employing hydroxypropyl-beta
      cyclodextrin (HP-beta-CD) as a mobile phase additive was developed. Various
      factors affecting the retention of isoflavone glycosides and aglycones in the
      C(18) reversed-phase column, such as the nature of cyclodextrins, HP-beta-CD
      concentration, and methanol concentration, were systematically studied. The
      results show that HP-beta-CD, as a very effective mobile phase additive, can
      markedly reduce the retention of isoflavone glycosides and aglycones, and the
      decrease magnitudes of isoflavone aglycones are more than those of their
      glycosides. The role of HP-beta-CD in the developed HPLC method is attributed to
      the formation of the inclusion complexes between isoflavone glycosides (or
      aglycones) and HP-beta-CD. So, the apparent formation constants of the isoflavone
      glycosides (or aglycones)/HP-beta-CD inclusion complexes also were investigated.
      Isoflavone glycosides (and aglycones) form the 1:1 inclusion complexes with HP
      beta-CD, and the isoflavone aglycones/HP-beta-CD complexes are more stable than
      the isoflavone glycosides/HP-beta-CD complexes. Finally, the optimized method was
      successfully applied for the determination of isoflavone glycosides and aglycones
      in Radix Astragali samples.

PMID- 23165722
TI  - Initial feasibility testing of limited field of view magnetic resonance
      thermometry using a local cardiac radiofrequency coil.
AB  - The visualization of lesion formation in real time is one potential benefit of
      carrying out radiofrequency ablation under magnetic resonance (MR) guidance in
      the treatment of atrial fibrillation. MR thermometry has the potential to detect
      such lesions. However, performing MR thermometry during cardiac radiofrequency
      ablation requires high temporal and spatial resolution and a high signal-to-noise
      ratio. In this study, a local MR coil (2-cm diameter) was developed to
      investigate the feasibility of performing limited field of view MR thermometry
      with high accuracy and speed. The local MR coil allowed high-resolution (1 * 1 *
      3 mm(3)) image acquisitions in 76.3 ms with a field of view 64 * 32 mm(2) during
      an open-chest animal experiment. This represents a 4-fold image acquisition
      acceleration and an 18-fold field of view reduction compared to that achieved
      using external MR coils. The signal sensitivity achieved using the local coil was
      over 20 times greater than that achievable using external coils with the same
      scan parameters. The local coil configuration provided fewer artifacts and
      sharper and more stable images. These results demonstrate that MR thermometry can
      be performed in the heart wall and that lesion formation can be observed during
      radiofrequency ablation procedures in a canine model.

PMID- 23165724
TI  - What controls the composition and the structure of nanomaterials generated by
      laser ablation in liquid solution?
AB  - Laser ablation synthesis in liquid solution (LASiS) is a "green" technique that
      gives access to the preparation of a library of nanomaterials. Bare noble metal
      spherical particles, multiphase core-shell oxides, metal-semiconductor
      heterostructures, layered organometallic compounds and other complex
      nanostructures can be obtained with the same experimental set up, just by varying
      a few synthetic parameters. How to govern such versatility is one of the current
      challenges of LASiS and requires a thorough understanding of the physical and
      chemical processes involved in the synthesis. In this perspective, the
      fundamental mechanisms of laser ablation in liquids are summarized, organized
      according to their temporal sequence and correlated with relevant examples taken
      from the library of nanomaterials disclosed by LASiS, in order to show how
      synthesis parameters influence the composition and the structure of products. The
      resulting framework suggests that, to date, much attention has been devoted to
      the physical aspects of laser-matter interaction and to the characterization of
      the final products of the synthesis. Conversely, the clarification of chemical
      processes active during LASiS deserves more research efforts and requires the
      synergy among multiple investigation techniques.

PMID- 23165723
TI  - Serum-free culture of primary human hepatocytes in a miniaturized hollow-fibre
      membrane bioreactor for pharmacological in vitro studies.
AB  - Primary human hepatocytes represent an important cell source for in vitro
      investigation of hepatic drug metabolism and disposition. In this study, a multi
      compartment capillary membrane-based bioreactor technology for three-dimensional
      (3D) perfusion culture was further developed and miniaturized to a volume of less
      than 0.5 ml to reduce demand for cells. The miniaturized bioreactor was composed
      of two capillary layers, each made of alternately arranged oxygen and medium
      capillaries serving as a 3D culture for the cells. Metabolic activity and
      stability of primary human hepatocytes was studied in this bioreactor in the
      presence of 2.5% fetal calf serum (FCS) under serum-free conditions over a
      culture period of 10 days. The miniaturized bioreactor showed functions
      comparable to previously reported data for larger variants. Glucose and lactate
      metabolism, urea production, albumin synthesis and release of intracellular
      enzymes (AST, ALT, GLDH) showed no significant differences between serum-free and
      serum-supplemented bioreactors. Activities of human-relevant cytochrome P450
      (CYP) isoenzymes (CYP1A2, CYP3A4/5, CYP2C9, CYP2D6, CYP2B6) analyzed by
      determination of product formation rates from selective probe substrates were
      also comparable in both groups. Gene expression analysis showed moderately higher
      expression in the majority of CYP enzymes, transport proteins and enzymes of
      Phase II metabolism in the serum-free bioreactors compared to those maintained
      with FCS. In conclusion, the miniaturized bioreactor maintained stable function
      over the investigated period and thus provides a suitable system for
      pharmacological studies on primary human hepatocytes under defined serum-free
      conditions.

PMID- 23165725
TI  - Producing ethnographies: workplace ethnographies in history.
AB  - Data on a large set of workplace ethnographies published from 1940 to 2002,
      compiled by Randy Hodson, are analyzed to show the trends over time in the
      production of such ethnographic work, its shifting disciplinary base, the
      relevance of the personal backgrounds of its authors, the contributions made by
      academic amateurs, the changing roles of gender and political stances, and the
      nature of different routes to publication. The definition of what counts as an
      ethnography is important to the character of the set available and has
      implications for its potential uses in secondary analysis. It is found that both
      personal and disciplinary identities and wider social factors have played roles
      in the production of ethnographic work that need to be understood to account for
      its history, though it is to be expected that the forms these take will differ
      for work in different subfields. 

PMID- 23165728
TI  - Direct nucleophilic addition to N-alkoxyamides.
AB  - While the synthesis of amide bonds is now one of the most reliable organic
      reactions, functionalization of amide carbonyl groups has been a long-standing
      issue due to their high stability. As an ongoing program aimed at practical
      transformation of amides, we developed a direct nucleophilic addition to N
      alkoxyamides to access multisubstituted amines. The reaction enabled installation
      of two different functional groups to amide carbonyl groups in one pot. The N
      alkoxy group played important roles in this reaction. First, it removed the
      requirement for an extra preactivation step prior to nucleophilic addition to
      activate inert amide carbonyl groups. Second, the N-alkoxy group formed a five
      membered chelated complex after the first nucleophilic addition, resulting in
      suppression of an extra addition of the first nucleophile. While
      diisobutylaluminum hydride (DIBAL-H) and organolithium reagents were suitable as
      the first nucleophile, allylation, cyanation, and vinylation were possible in the
      second addition including inter- and intramolecular reactions. The yields were
      generally high, even in the synthesis of sterically hindered alpha-trisubstituted
      amines. The reaction exhibited wide substrate scope, including acyclic amides,
      five- and six-membered lactams, and macrolactams.

PMID- 23165727
TI  - EphrinB2/EphB4 inhibition in the osteoblast lineage modifies the anabolic
      response to parathyroid hormone.
AB  - Previous reports indicate that ephrinB2 expression by osteoblasts is stimulated
      by parathyroid hormone (PTH) and its related protein (PTHrP) and that
      ephrinB2/EphB4 signaling between osteoblasts and osteoclasts stimulates
      osteoblast differentiation while inhibiting osteoclast differentiation. To
      determine the role of the ephrinB2/EphB4 interaction in the skeleton, we used a
      specific inhibitor, soluble EphB4 (sEphB4), in vitro and in vivo. sEphB4
      treatment of cultured osteoblasts specifically inhibited EphB4 and ephrinB2
      phosphorylation and reduced mRNA levels of late markers of osteoblast/osteocyte
      differentiation (osteocalcin, dentin matrix protein-1 [DMP-1], sclerostin, matrix
      extracellular phosphoglycoprotein [MEPE]), while substantially increasing RANKL.
      sEphB4 treatment in vivo in the presence and absence of PTH increased osteoblast
      formation and mRNA levels of early osteoblast markers (Runx2, alkaline
      phosphatase, Collagen 1alpha1, and PTH receptor [PTHR1]), but despite a
      substantial increase in osteoblast numbers, there was no significant change in
      bone formation rate or in late markers of osteoblast/osteocyte differentiation.
      Rather, in the presence of PTH, sEphB4 treatment significantly increased
      osteoclast formation, an effect that prevented the anabolic effect of PTH,
      causing instead a decrease in trabecular number. This enhancement of
      osteoclastogenesis by sEphB4 was reproduced in vitro but only in the presence of
      osteoblasts. These data indicate that ephrinB2/EphB4 signaling within the
      osteoblast lineage is required for late stages of osteoblast differentiation and,
      further, restricts the ability of osteoblasts to support osteoclast formation, at
      least in part by limiting RANKL production. This indicates a key role for the
      ephrinB2/EphB4 interaction within the osteoblast lineage in osteoblast
      differentiation and support of osteoclastogenesis.

PMID- 23165729
TI  - Sequence-dependent assembly to control molecular interface properties.
AB  - Variation's what you need: variation of the assembly sequence in which layers of
      two isostructural metal complexes are built up leads to molecular materials with
      electrochemical properties that depend on the assembly sequence. These properties
      vary from reversible electron transfer to unidirectional current flows and even
      charge trapping. The sequence-dependent assembly strategy has implications for
      various disciplines that involve self-assembly.

PMID- 23165726
TI  - Clinical geneticists' views of VACTERL/VATER association.
AB  - VACTERL association (sometimes termed "VATER association" depending on which
      component features are included) is typically defined by the presence of at least
      three of the following congenital malformations, which tend to statistically co
      occur in affected individuals: Vertebral anomalies, Anal atresia, Cardiac
      malformations, Tracheo-Esophageal fistula, Renal anomalies, and Limb
      abnormalities. Although the clinical criteria for VACTERL association may appear
      to be straightforward, there is wide variability in the way clinical geneticists
      define the disorder and the genetic testing strategy they use when confronted
      with an affected patient. In order to describe this variability and determine the
      most commonly used definitions and testing modalities, we present the results of
      survey responses by 121 clinical geneticists. We discuss the results of the
      survey responses, provide a literature review and commentary from a group of
      physicians who are currently involved in clinical and laboratory-based research
      on VACTERL association, and offer an algorithm for genetic testing in patients
      with this association.

PMID- 23165730
TI  - Priorities, satisfaction and treatment goals in psychosis patients: an online
      consumer's survey.
AB  - BACKGROUND: An insight into preferences, satisfaction and treatment goals of
      patients is important for reaching treatment alliance and may increase the
      success of initiated treatment. METHODS: Participants from the Netherlands,with
      at least one psychotic episode, were asked to fill in an online questionnaire.
      Participants ranked their priorities in treatment content, stated whether they
      were satisfied on these items and ranked a list of treatment goals. RESULTS: 462
      respondents ranked their treatment preferences regarding treatment content(mean
      age: 40.3 years; mean duration of illness: 13.5 years). Items ranked most
      important: "prompt assistance, preferably in own environment", "attention for
      medication", "appropriate attitude of the professional caregiver". More than 50 %
      rated "unsatisfied" or "very unsatisfied" for: "practical help in
      resocialization", "aid to acquire autonomy" and "help with physical health". 345
      participants ranked treatment goals (mean age: 40.4 years; mean duration of
      illness: 13.7 years). Items ranked most important: "reducing apathy and lack of
      initiative", "reducing disturbing or unusual experiences", "reducing confusion
      and concentration problems". CONCLUSION: Psychiatric services should pay great
      attention to early outpatient intervention with supportive counseling and an
      appropriate attitude of the caregiver with attention for medication use.
      Improvement is warranted for practical assistance, help in regaining autonomy and
      help with physical health.

PMID- 23165731
TI  - Brain perfusion imaging: How does it work and what should I use?
AB  - In the last 15 years there has been a relative explosion in the number of
      magnetic resonance imaging (MRI) techniques and developments related to cerebral
      perfusion. Given the variety of perfusion methods available, it is often
      difficult to decide which technique would be best for a particular clinical
      question or patient. In this review article we discuss the more common
      techniques, review how they are performed, and summarize the optimal technique or
      techniques for a variety of clinical situations.

PMID- 23165732
TI  - Evaluation of chondral repair using quantitative MRI.
AB  - Various quantitative magnetic resonance imaging (qMRI) biomarkers, including but
      not limited to parametric MRI mapping, semiquantitative evaluation, and
      morphological assessment, have been successfully applied to assess cartilage
      repair in both animal and human studies. Through the interaction between
      interstitial water and constituent macromolecules the compositional and
      structural properties of cartilage can be evaluated. In this review a
      comprehensive view of a variety of quantitative techniques, particularly those
      involving parametric mapping, and their relationship to the properties of
      cartilage repair is presented. Some techniques, such as T2 relaxation time
      mapping and delayed gadolinium-enhanced MRI of cartilage (dGEMRIC), are well
      established, while the full potential of more recently introduced techniques
      remain to be demonstrated. A combination of several MRI techniques is necessary
      for a comprehensive characterization of chondral repair.

PMID- 23165733
TI  - Hyperpolarized 13C metabolic imaging using dissolution dynamic nuclear
      polarization.
AB  - This article describes the basic physics of dissolution dynamic nuclear
      polarization (dissolution-DNP), and the impact of the resulting highly
      nonequilibrium spin states, on the physics of magnetic resonance imaging (MRI)
      detection. The hardware requirements for clinical translation of this technology
      are also presented. For studies that allow the use of externally administered
      agents, hyperpolarization offers a way to overcome normal magnetic resonance
      sensitivity limitations, at least for a brief T(1)-dependent observation window.
      A 10,000-100,000-fold signal-to-noise advantage provides an avenue for real-time
      measurement of perfusion, metabolite transport, exchange, and metabolism. The
      principles behind these measurements, as well as the choice of agent, and
      progress toward the application of hyperpolarized (13)C metabolic imaging in
      oncology, cardiology, and neurology are reviewed.

PMID- 23165736
TI  - Two-photon microscopy of the mouse cochlea in situ for cellular diagnosis.
AB  - Sensorineural hearing loss is the most common type of hearing loss worldwide, yet
      the underlying cause is typically unknown because the inner ear cannot be
      biopsied today without destroying hearing, and intracochlear cells have not been
      imaged with resolution sufficient to establish diagnosis. Intracochlear imaging
      has been technologically challenging because of the cochlea's small size and
      encasement in bone. We report, for the first time, imaging of the mouse cochlea
      in situ without exogenous dyes, through a membranous round window, using a near
      infrared femtosecond laser as the excitation and endogenous two-photon excitation
      fluorescence (TPEF) and second harmonic generation as the contrast mechanisms. We
      find that TPEF exhibits strong contrast allowing cellular, and even subcellular
      resolution, and detection of specific, noise-induced pathologic changes. Our
      results demonstrate that the round window provides a useful access to the cochlea
      through the middle ear, and they motivate future development of a new and
      efficient diagnostic tool based on two-photon micro-endoscopy.

PMID- 23165737
TI  - Bipyridine and phenanthroline IR-spectral bands as indicators of metal spin state
      in hexacoordinated complexes of Fe(II), Ni(II) and Co(II).
AB  - Possible stable structures of various 2,2'-bipyridine (bpy) and 1,10
      phenanthroline (phen) complexes, [Ni(bpy)(3)](2+), [Co(bpy)(3)](2+),
      [Fe(bpy)(3)](2+) and Fe(phen)(2)(NCS)(2), were optimized for different spin
      states of the metals, and the spectra computed for every form were compared with
      the experimental IR spectra of the compounds. It is demonstrated that the changes
      in spin states of the metals influence both geometry and vibrational spectra of
      the complexes. Spectral changes are predicted not only in the low frequency
      range, corresponding to metal-ligand vibrations, but also in the mid-IR range,
      where ligand vibrations are active. Detailed computational analysis in
      combination with the corresponding spectroscopic experiment shows that the
      spectral changes are of a similar character for complexes with the same ligands
      independent on the central metal and can be used as spectroscopic markers of the
      electronic state of the latter. Found spectral markers have been validated at a
      number of complexes of Fe(II), Ni(II), Co(II), Zn(II) and Cu(II) with bpy and
      phen ligands.

PMID- 23165739
TI  - Pruritic and vascular responses induced by serotonin in patients with atopic
      dermatitis and in healthy controls.
AB  - Atopic dermatitis (AD) is a chronic inflammatory skin disease with often severe
      itch. The aim of this study was to determine the pruritogenic and vascular effect
      of serotonin (5-hydroxytryptamine; 5-HT) in patients with AD and in healthy
      controls. A 50 ug dose of 5-HT was injected intradermally into non-lesional skin
      of 25 patients with AD and 25 healthy control individuals, and the effect
      compared with 0.2 ug histamine as a positive control, and buffer as a negative
      control. Pruritus was recorded by the subjects, using a computerized visual
      analogue scale, while flare and wheal were recorded by the investigator. There
      was no qualitative or quantitative difference in 5-HT-induced itch between
      patients and control subjects, or between males and females. However, reduced
      flare and wheal were found in the patient group for 5-HT. There were no
      correlations between clinical findings (i.e. eczema severity, clinical pruritus)
      and recorded experimental itch, or flare or wheal responses for 5-HT, in the
      patients with AD. In both groups a shorter itch latency was found for 5-HT
      compared with histamine. Through the use of intradermal injections, making it
      possible to calculate the dose of substance delivered, a lower vascular response
      to 5-HT was shown in patients with AD compared with healthy controls. In addition
      to confirming a pruritogenic role of 5-HT in both patients with AD and healthy
      controls, we found a shorter itch latency for 5-HT compared with histamine in
      both groups. The short itch latency time may indicate a direct effect of 5-HT on
      itch receptors.

PMID- 23165740
TI  - From Wald to Savage: homo economicus becomes a Bayesian statistician.
AB  - Bayesian rationality is the paradigm of rational behavior in neoclassical
      economics. An economic agent is deemed rational when she maximizes her subjective
      expected utility and consistently revises her beliefs according to Bayes's rule.
      The paper raises the question of how, when and why this characterization of
      rationality came to be endorsed by mainstream economists. Though no definitive
      answer is provided, it is argued that the question is of great historiographic
      importance. The story begins with Abraham Wald's behaviorist approach to
      statistics and culminates with Leonard J. Savage's elaboration of subjective
      expected utility theory in his 1954 classic The Foundations of Statistics. The
      latter's acknowledged fiasco to achieve a reinterpretation of traditional
      inference techniques along subjectivist and behaviorist lines raises the puzzle
      of how a failed project in statistics could turn into such a big success in
      economics. Possible answers call into play the emphasis on consistency
      requirements in neoclassical theory and the impact of the postwar transformation
      of U.S. business schools. 

PMID- 23165741
TI  - Stiffness- and wettability-dependent myoblast cell compatibility of transparent
      poly(vinyl alcohol) hydrogels.
AB  - This study reports the in vitro compatibility of muscle cells (C2C12 mouse
      myoblast cell line) with the transparent poly(vinyl alcohol) (PVA) hydrogels and
      the results are explained on the basis of surface wettability, crystallinity, and
      nanoscale elastic stiffness property. Nanoindentation was carried out with a
      maximum load of 100 MUN for all the hydrogel compositions and the properties such
      as elastic stiffness, hardness and total work done during indentation were
      computed. The difference in cell viability as well as adhesion of cultured
      myoblast cells on the investigated hydrogel substrates were discussed in
      reference to the difference in the nanoscale elastic properties, crystallinity,
      and surface wettability. An important result has been that both elastic stiffness
      and surface wettability synergistically influence myoblast viability/adhesion on
      PVA hydrogels.

PMID- 23165742
TI  - Seroprevalence of Trypanosoma cruzi and Leishmania mexicana in free-ranging
      howler monkeys in southeastern Mexico.
AB  - Natural infection of wild mammals by protozoa parasites is quite common in
      nature. For Neotropical Primates different infections of parasites that are
      etiological agent of disease in human have been identified. In particular,
      infections by Trypanosoma cruzi and Leishmania sp., have been reported for some
      New World primate species, but there are no reports of infection with these
      parasites in any primate species in Mexico. A serological study was conducted on
      two howler monkey species (Alouatta pigra and A. palliata) from the Mexican
      states of Campeche and Tabasco. A total of 55 serum samples (20 samples from A.
      pigra, 20 samples from A. palliata, and 15 samples from semifree ranging A.
      palliata of Los Tuxtlas, Veracruz as negative controls) were analyzed for the
      detection of immunoglobulin G antibodies against T. cruzi and Leishmania mexicana
      through enzyme linked immunosorbent assay test, indirect immunofluorescence assay
      and Western blot. The overall prevalence of antibodies in howler monkeys was
      17.5% for T. cruzi and 30% for L. mexicana. Our results also indicate that A.
      pigra is more susceptible to develop leishmaniasis than A. palliata. Finally, the
      finding of positive serology in these primates should be given serious
      consideration for public health, given the potential role of these primate
      species as wild reservoirs for these diseases and the increasing contact of
      monkeys with human populations due to habitat loss and fragmentation.

PMID- 23165743
TI  - Single-fraction radiotherapy versus multifraction radiotherapy for palliation of
      painful vertebral bone metastases-equivalent efficacy, less toxicity, more
      convenient: a subset analysis of Radiation Therapy Oncology Group trial 97-14.
AB  - BACKGROUND: The Radiation Therapy Oncology Group (RTOG) trial 97-14 revealed no
      difference between radiation delivered for painful bone metastases at a dose of 8
      gray (Gy) in 1 fraction (single-fraction radiotherapy [SFRT]) and 30 Gy in 10
      fractions (multifraction radiotherapy [MFRT]) in pain relief or narcotic use 3
      months after randomization. SFRT for painful vertebral bone metastases (PVBM) has
      not been well accepted, possibly because of concerns about efficacy and toxicity.
      In the current study, the authors evaluated the subset of patients that was
      treated specifically for patients with PVBM. METHODS: PVBM included the cervical,
      thoracic, and/or lumbar spine regions. Among patients with PVBM, differences in
      retreatment rates and in pain relief, narcotic use, and toxicity 3 months after
      randomization were evaluated. RESULTS: Of 909 eligible patients, 235 (26%) had
      PVBM. Patients with and without PVBM differed in terms of the percentage of men
      (55% vs 47%, respectively; P = .03) and the proportion of patients with multiple
      painful sites (57% vs 38%, respectively; P < .01). Among those with PVBM, more
      patients who received MFRT had multiple sites treated (65% vs 49% for MFRT vs
      SFRT, respectively; P = .02). There were no statistically significant treatment
      differences in terms of pain relief (62% vs 70% for MFRT vs SFRT, respectively; P
      = .59) or freedom from narcotic use (24% vs 27%, respectively; P = .76) at 3
      months. Significant differences in acute grade 2 through 4 toxicity (20% vs 10%
      for MFRT vs SFRT, respectively; P = .01) and acute grade 2 through 4
      gastrointestinal toxicity (14% vs 6%, respectively; P = .01) were observed at 3
      months, with lower toxicities seen in the patients treated with SFRT. Late
      toxicity was rare. No myelopathy was recorded. SFRT produced higher 3-year
      retreatment rates (5% vs 15%; P = .01). CONCLUSIONS: Results for the subset of
      patients with PVBM in the RTOG 94-17 randomized controlled trial were comparable
      to those for the entire population. SFRT produced less acute toxicity and a
      higher rate of retreatment than MFRT. SFRT and MFRT resulted in comparable pain
      relief and narcotic use at 3 months.

PMID- 23165744
TI  - Purification and characterization of a novel antifungal protein with
      antiproliferation and anti-HIV-1 reverse transcriptase activities from Peganum
      harmala seeds.
AB  - A novel antifungal protein, designated as PHP, was isolated from the seeds of
      Peganum harmala, by cationic exchange chromatography on Resource S column and gel
      filtration on Sephadex 75 10/300 GL column. PHP was found to form a homodimer of
      about 16 kDa. Isoelectric focusing polyacrylamide gel electrophoresis analysis
      showed that the isoelectric point of PHP was ~8.4. The N-terminal 20-amino acid
      sequence of PHP, ITCPQVTQSLAPCVPYLISG, resembles the non-specific lipid transfer
      proteins in certain plants. PHP exhibited lipid-binding activity. Furthermore,
      PHP exerted antifungal activity against Alternaria alternate, Penicillium
      degitatum, Rhizopus stuolonifer, and Magnaporthe grisea, and its antifungal
      activity was stable in the temperature range 4-60 degrees C, and in the pH range
      4-10. It inhibited the mycelial growth in A. alternate, P. degitatum, R.
      stuolonifer, and M. grisea with 50% inhibitory concentration (IC(50)) of 1.5,
      37.5, 8.44, and 12.19 MUM, respectively. PHP was also able to inhibit the
      proliferation of esophagus carcinoma (Eca-109), cervical carcinoma (HeLa),
      gastric carcinoma (MGC-7), and melanoma (B16) cells with IC(50) of 0.7, 2.74,
      3.13, and 1.47 MUM, respectively. Moreover, PHP significantly inhibited HIV-1
      reverse transcriptase (RT) with an IC(50) of 1.26 MUM. It did not have
      hemagglutinating and antibacterial activities. In conclusion, a novel antifungal
      protein with antiproliferation and anti-HIV-1 RT activities was obtained from P.
      harmala seeds.

PMID- 23165745
TI  - Endosomal cholesterol trafficking: protein factors at a glance.
AB  - The delivery of low-density lipoprotein-derived cholesterol (LDL-C) from
      endosomal compartments to the plasma membrane and the endoplasmic reticulum (ER)
      is an important yet poorly understood cellular process. Niemann-Pick C1 (NPC1), a
      multi-pass integral membrane protein on the limiting membranes of late endosomes
      (LE)/lysosomes (Ly), is known to insert lumenal LDL-C to the limiting membrane of
      LE/Ly. Recent progress has identified novel cytoplasmic proteins that regulate
      the exit of LDL-C from LE/Ly, such as ORP5, a member of the oxysterol-binding
      protein-related protein (ORPs) family, and Hrs/VPS27, a well-established
      regulator of the endosomal sorting complex required for transport pathway.
      Whereas ORP5/ORPs may serve as cytosolic cholesterol carriers and deliver
      cholesterol in a non-vesicular manner, how Hrs/VPS27 regulate endosomal
      cholesterol sorting remains enigmatic. We discuss the functional relationship
      between NPC1, Hrs, and ORP5, and formulate possible schemes on how LDL-C may be
      moved from endosomal compartments to other cellular organelles.

PMID- 23165746
TI  - Adeno-associated virus Rep78 restricts adenovirus E1B55K-mediated p53 nuclear
      exportation.
AB  - Inactivation of p53 is needed during adenovirus type 5 DNA replication. E1B55K,
      an adenovirus early protein, has been reported to interact with p53 and inhibit
      p53 transactivation. Previous studies have shown that adeno-associated virus
      (AAV) type 2 could reduce the transforming potential of adenovirus by rescuing
      p53 from adenovirus-mediated degradation, but the details are not clear yet. We
      detected the Rep78-p53 interaction by co-immunoprecipitation assay. The co
      localization assay revealed that Rep78 inhibits E1B55K-mediated p53 nuclear
      exportation. However, Rep78 did not detectably influence p53 stability and could
      not relieve the transcriptional inactivation of p53, as E1B55K could not be
      replaced from the p53-E1B55K complex by Rep78. Our results reveal a new possible
      mechanism that AAV-2 Rep78 inhibits adenovirus 5 by relocalizing p53 in the
      nucleus, which may shed some light on the regulatory mechanism of AAV-2 on its
      helper virus, adenovirus.

PMID- 23165747
TI  - Tensor tympani motoneurons receive mostly excitatory synaptic inputs.
AB  - The tensor tympani is a middle ear muscle that contracts in two different
      situations: in response to sound or during voluntary movements. To gain insight
      into the inputs and neural regulation of the tensor tympani, we examined the
      ultrastructure of synaptic terminals on labeled tensor tympani motoneurons
      (TTMNs) using transmission electron microscopy. Our sample of six TTMNs received
      79 synaptic terminals that formed 126 synpases. Two types of synapses are
      associated with round vesicles and form asymmetric junctions (excitatory
      morphology). One of these types has vesicles that are large and round (Lg Rnd)
      and the other has vesicles that are smaller and round (Sm Rnd) and also contains
      at least one dense core vesicle. A third synapse type has inhibitory morphology
      because it forms symmetric synapses with pleomorphic vesicles (Pleo). These
      synaptic terminals can be associated with TTMN spines. Two other types of synapse
      are found on TTMNs but they are uncommon. Synaptic terminals of all types form
      multiple synapses but those from a single terminal are always the same type.
      Terminals with Lg Rnd vesicles formed the most synpases per terminal (avg. 2.73).
      Together, the synaptic terminals with Lg Rnd and Sm Rnd vesicles account for 62%
      of the terminals on TTMNs, and they likely represent the pathways driving the
      contractions in response to sound or during voluntary movements. Having a high
      proportion of excitatory inputs, the TTMN innervation is like that of stapedius
      motoneurons but proportionately different from other types of motoneurons.

PMID- 23165748
TI  - Trichostatin A induces apoptotic cell death of HeLa cells in a Bcl-2 and
      oxidative stress-dependent manner.
AB  - Trichostatin A (TSA) as a HDAC inhibitor can regulate many biological properties
      including apoptosis and cell proliferation in various cancer cells. Here, we
      evaluated the effect of TSA on the growth and death of HeLa cervical cancer cells
      in relation to reactive oxygen species (ROS) and glutathione (GSH) levels. Dose-
      and time-dependent growth inhibition was observed in HeLa cells with an IC50 of
      approximately 20 nM at 72 h. This agent also induced apoptotic cell death, as
      evidenced by annexin V-FITC staining cells, caspase-3 activation and the loss of
      mitochondrial membrane potential (MMP; ?psim). In addition, the administration of
      Bcl-2 siRNA intensified TSA-induced HeLa cell death. All of the tested caspase
      inhibitors significantly rescued some cells from TSA-induced HeLa cell death. TSA
      increased O2*- level and induced GSH depletion in HeLa cells. Caspase inhibitors
      significantly attenuated O2*- level and GSH depletion in TSA-treated HeLa cells.
      In addition, N-acetyl cysteine (NAC; a well known antioxidant) significantly
      prevented cell death and GSH depletion in TSA-treated HeLa cells via decreasing
      O2*- level. In conclusion, TSA inhibited the growth of HeLa cells via Bcl-2
      mediated apoptosis, which was closely related to O2*- and GSH content levels.

PMID- 23165749
TI  - High-throughput profiling of N-myristoylation substrate specificity across
      species including pathogens.
AB  - One of the most critical modifications affecting the N-terminus of proteins is N
      myristoylation. This irreversible modification affects the membrane-binding
      properties of crucial proteins involved in signal transduction cascades. This
      cotranslational modification, catalyzed by N-myristoyl transferase, occurs both
      in lower and higher eukaryotes and is a validated therapeutic target for several
      pathologies. However, this lipidation proves very difficult to be evidenced in
      vivo even with state-of-the-art proteomics approaches or bioinformatics tools. A
      large part of N-myristoylated proteins remains to be discovered and the rules of
      substrate specificity need to be established in each organism. Because the
      peptide substrate recognition occurs around the first eight residues, short
      peptides are used for modeling the reaction in vitro. Here, we provide a novel
      approach including a dedicated peptide array for high-throughput profiling
      protein N-myristoylation specificity. We show that myristoylation predictive
      tools need to be fine-tuned to organisms and that their poor accuracy should be
      significantly enhanced. This should lead to strongly improved knowledge of the
      number and function of myristoylated proteins occurring in any proteome.

PMID- 23165751
TI  - Medical complications, clinical findings, and educational outcomes in adults with
      Noonan syndrome.
AB  - Noonan syndrome (NS) is a heterogeneous developmental disorder caused by missense
      mutations in genes involved in the Ras/MAPK signaling pathway, a major mediator
      of early and late developmental processes. The diagnosis of NS is made on
      clinical grounds with molecular confirmation of a mutation found in 63% of cases.
      Key clinical features include short stature, cardiac defects, developmental
      delay, lymphatic dysplasias, bleeding tendency, and a constellation of
      distinctive facial features and physical exam findings. The prevalence of medical
      issues or the development of new ones in adults with NS is not well-studied. This
      cross-sectional study reports on the prevalence of clinical conditions and their
      ages of onset in a cohort of 35 adolescents and adults with NS aged 16-68 years
      old (mean age 28 years). In this cohort, 34 of 35 subjects (97%) had had full
      PTPN11 sequencing; 37% were PTPN11 positive, 23% were SOS1 positive, and 3% were
      BRAF positive. Mean adult height in both men and women was at the 3rd-10th
      centile. The most prevalent clinical findings in this cohort included pulmonary
      valve stenosis (71%), easy bruising (63%), GERD (60%), constipation (51%),
      scoliosis (54%), chronic joint pain (54%), lymphedema (49%), depression (49%),
      anxiety (49%), Chiari malformation (20%), and osteopenia/osteoporosis (14%). In
      summary, adults with NS are affected by multi-organ morbidity and require special
      medical management aimed towards the most prevalent and serious known medical
      complications. Larger studies characterizing the clinical conditions found in NS
      adults are needed to provide potential genotype-phenotype correlations that may
      aid in clinical management.

PMID- 23165750
TI  - Localization errors in MR spectroscopic imaging due to the drift of the main
      magnetic field and their correction.
AB  - PURPOSE: To analyze the effect of B0 field drift on multivoxel MR spectroscopic
      imaging and to propose an approach for its correction. THEORY AND METHODS: It is
      shown, both theoretically and in a phantom, that for ~30 min acquisitions a
      linear B0 drift (~0.1 ppm/h) will cause localization errors that can reach
      several voxels (centimeters) in the slower varying phase encoding directions. An
      efficient and unbiased estimator is proposed for tracking the drift by
      interleaving short (~ T2*), nonlocalized acquisitions on the nonsuppressed water
      each pulse repetition time, as shown in 10 volunteers at 1.5 and 3 T. RESULTS:
      The drift is shown to be predominantly linear in both the phantom and volunteers
      at both fields. The localization errors are observed and quantified in both
      phantom and volunteers. The unbiased estimator is shown to reliably track the
      instantaneous frequency in vivo despite only using a small portion of the FID.
      CONCLUSION: Contrary to single-voxel MR spectroscopy, where it leads to line
      broadening, field drift can lead to localization errors in the longer chemical
      shift imaging experiments. Fortunately, this drift can be obtained at a
      negligible cost to sequence timing, and corrected for in post processing.

PMID- 23165752
TI  - Image analysis tools to quantify cell shape and protein dynamics near the leading
      edge.
AB  - We present a set of flexible image analysis tools to analyze dynamics of cell
      shape and protein concentrations near the leading edge of cells adhered to glass
      coverslips. Plugins for ImageJ streamline common analyses of microscopic images
      of cells, including the calculation of leading edge speeds, total and average
      intensities of fluorescent markers, and retrograde flow rate measurements of
      fluorescent single-molecule speckles. We also provide automated calculations of
      auto- and cross-correlation functions between velocity and intensity
      measurements. The application of the methods is illustrated on images of XTC
      cells.

PMID- 23165753
TI  - Pentaquinone based probe for nanomolar detection of zinc ions: chemosensing
      ensemble as an antioxidant.
AB  - A pentaquinone based compound 3a has been synthesized which undergoes significant
      fluorescence enhancement in the presence of Zn(2+) ions with a detection limit up
      to nanomolar range in THF. Further, the zinc ensemble of 3a is evaluated for its
      anti-oxidizing property which is better than commercially available antioxidants.

PMID- 23165754
TI  - EphB4 enhances the process of endochondral ossification and inhibits remodeling
      during bone fracture repair.
AB  - Previous reports have identified a role for the tyrosine kinase receptor EphB4
      and its ligand, ephrinB2, as potential mediators of both bone formation by
      osteoblasts and bone resorption by osteoclasts. In the present study, we examined
      the role of EphB4 during bone repair after traumatic injury. We performed femoral
      fractures with internal fixation in transgenic mice that overexpress EphB4 under
      the collagen type 1 promoter (Col1-EphB4) and investigated the bone repair
      process up to 12 weeks postfracture. The data indicated that Col1-EphB4 mice
      exhibited stiffer and stronger bones after fracture compared with wild-type mice.
      The fractured bones of Col1-EphB4 transgenic mice displayed significantly greater
      tissue and bone volume 2 weeks postfracture compared with that of wild-type mice.
      These findings correlated with increased chondrogenesis and mineral formation
      within the callus site at 2 weeks postfracture, as demonstrated by increased
      safranin O and von Kossa staining, respectively. Interestingly, Col1-EphB4 mice
      were found to possess significantly greater numbers of clonogenic mesenchymal
      stromal progenitor cells (CFU-F), with an increased capacity to form mineralized
      nodules in vitro under osteogenic conditions, when compared with those of the
      wild-type control mice. Furthermore, Col1-EphB4 mice had significantly lower
      numbers of TRAP-positive multinucleated osteoclasts within the callus site. Taken
      together, these observations suggest that EphB4 promotes endochondral
      ossification while inhibiting osteoclast development during callus formation and
      may represent a novel drug target for the repair of fractured bones.

PMID- 23165755
TI  - A luminescent metal-organic framework as a turn-on sensor for DMF vapor.
AB  - A real turn-on: a luminescent lanthanide metal-organic framework shows strong and
      fast turn-on responses to N,N-dimethylformamide (DMF) vapor. The selective turn
      on effect is triggered mainly by DMF-ligand interactions, along with the removal
      of quencher, water, from the metal coordination sphere.

PMID- 23165756
TI  - Stepwise degradation of trifluoromethyl platinum(II) compounds.
AB  - The action of moisture on the homoleptic organoplatinum(II) compound
      [NBu(4)](2)[Pt(CF(3))(4)] (1) gives rise to the carbonyl derivative
      [NBu(4)][Pt(CF(3))(3)(CO)] (2), which is itself moisture stable. However,
      treatment of compound 2 with HCl(aq) results in the formation of [NBu(4)][cis
      Pt(CF(3))(2)Cl(CO)] (3), which undergoes degradation of an additional CF(3) group
      by further treatment with HCl(aq) in large excess, affording [NBu(4)][cis
      Pt(CF(3))Cl(2)(CO)] (4). The carbonyl derivatives 2-4 are fairly stable species,
      in which the CO ligand, however, can be readily extruded by reaction with
      trimethylamine N-oxide (ONMe(3)). Thus, compound 2 reacts with ONMe(3) in the
      presence of a number of neutral or anionic ligands affording a series of singly
      or doubly charged derivatives with the general formulae [NBu(4)][Pt(CF(3))(3)(L)]
      [L = CNtBu (5), PPh(3) (6), P(o-tolyl)(3) (7), tht (8; tht =
      tetrahydrothiophene)] and [NBu(4)](2)[Pt(CF(3))(3)X] [X = Cl (9), Br (10), I
      (11)], respectively. Compound 2 also reacts with ONMe(3) and pyridin-2-thiol
      (C(5)H(5)NS) giving rise to the five-membered metallacyclic derivative
      [NBu(4)][Pt(CF(3))(2)(CF(2)NC(5)H(4)S-kappaC,kappaS)] (12), which can be viewed
      as a difluorocarbene species stabilized by intramolecular base coordination. On
      the other hand, treatment of compound 3 with ONMe(3) in the presence of
      C(5)H(5)NS yields the four-membered metallacyclic compound
      [NBu(4)][Pt(CF(3))(2)(NC(5)H(4)S-kappaN,kappaS)] (13). The geometries of the
      metallacycles in compounds 12 and 13 are compared. In the absence of any
      additional ligand, compound 3 undergoes dimerization producing the dinuclear
      species [NBu(4)](2)[{Pt(CF(3))(2)}(2)(MU-Cl)(2)] (14). Halide abstraction in the
      latter compound with AgClO(4) in THF yields the solvento compound cis
      [Pt(CF(3))(2)(thf)(2)] (15). The highly labile character of the THF ligands in
      compound 15 makes this species a convenient synthon of the "cis-Pt(CF(3))(2)"
      unit.

PMID- 23165757
TI  - Downward trend in the risk of second myocardial infarction in Sweden, 1987-2007:
      breakdown by socioeconomic position, gender, and country of birth.
AB  - BACKGROUND: Second myocardial infarction (SMI) is a significant health problem.
      There are no nationwide studies on SMI among foreign-born populations that
      include detailed information about country of birth. DESIGN: Nationwide cohort
      study of 331,748 men and 186,755 women aged 30-84, living in Sweden, and
      diagnosed with first myocardial infarction (FMI) between January 1987 and
      December 2007. METHODS: Trends in, and risk of, SMI after day 28 of FMI
      association with gender, educational level, and country of birth were analysed. A
      hazard ratio (HR) with a 95% confidence interval (CI) yielded a risk estimate of
      SMI among FMI patients based on the Cox proportional hazard model. RESULTS: Men
      had a higher risk of SMI than women (HR 1.14, 95% CI 1.12-1.55) with a downward
      trend over time, regardless of country of birth (p-trend <0.0001). Low
      educational level increased the HR of SMI irrespective of gender or country of
      birth. Foreign-born men and women had a slightly increased HR than Sweden-born.
      Men born in India, Palestine, Uganda, Algeria, and Tunisia and women born in
      India, Palestine, and Lebanon had approximately a 2-fold risk. Men born in the
      Netherlands had the lowest risk (HR 0.65, 95% CI 0.44-0.94). Foreign-born who had
      lived in Sweden for less than 35 years had a higher risk than those that had
      lived there for 35 years or longer. CONCLUSIONS: Although the risk of SMI
      continued to decrease over time, low socioeconomic position independent of
      country of birth and gender remained an important risk indicator deserving
      further attention.

PMID- 23165758
TI  - Recurrent chylous pericardial effusion and left neck mass.
AB  - We present a case of a woman initially presenting with a neck mass and
      subsequently found to have generalized lymphatic anomaly with diffuse lymphatic
      dilation and proliferation involving the mediastinum and pericardium.
      Intrathoracic involvement of generalized lymphatic anomalies can lead to
      recurrent pleural effusions, pericardial effusions, and severe respiratory
      infections. These anomalies cannot be cured and significantly impact quality of
      life. Multidisciplinary involvement is crucial to maximize symptom relief as
      surgery to remove lymphatics can be morbid and the disease is usually recurrent.

PMID- 23165759
TI  - Management and outcomes of patients on preoperative plavix (clopidogrel)
      undergoing general thoracic surgery.
AB  - OBJECTIVES: Plavix (clopidogrel) is a potent antiplatelet agent used to prevent
      thrombosis in a variety of clinical settings. The perioperative management of
      thoracic surgery patients who are on clopidogrel at the time of surgery is not
      well defined. We conducted this review to examine the perioperative management
      and outcomes of patients undergoing general thoracic surgical procedures.
      METHODS: From January 2005 to January 2010, 165 patients on clopidogrel underwent
      182 operative procedures. Three management strategies were identified: Group I:
      clopidogrel continued through surgery (n = 17), Group II: clopidogrel
      discontinued with a bridging agent (n = 44) and Group III clopidogrel
      discontinued without a bridging agent (n = 121). Propensity score matched cohorts
      (17 clopidogrel continued; 34 clopidogrel discontinued) were constructed based on
      age, clopidogrel indication, American Society of Anesthesiology status, and
      procedure and used to compare the impact of clopidogrel management on
      postoperative bleeding and cardiovascular morbidity. RESULTS: Unmatched analysis
      revealed a significantly higher rate of transfusion in the group of patients who
      continued on clopidogrel throughout the perioperative period, compared with
      patients who had clopidogrel discontinued. Although there were more
      cardiovascular events in Groups II and III, there were no significant differences
      between groups in postoperative mortality, myocardial infarction, stroke, or
      reoperation for bleeding. In propensity matched patients only the rate of
      postoperative transfusions was significantly higher in patients continued on
      clopidogrel compared with patients whose clopidogrel was discontinued (35.3 vs.
      2.9%), p < 0.004. CONCLUSIONS: In selected patients, some thoracic surgical
      procedures can be performed safely on clopidogrel but are associated with higher
      rates of postoperative transfusion.

PMID- 23165760
TI  - Hydrogen storage of a novel combined system of LiNH2-NaMgH3: synergistic effects
      of in situ formed alkali and alkaline-earth metal hydrides.
AB  - Bimetallic hydride NaMgH(3) is used for the first time as a vehicle to enhance
      hydrogen release and uptake from LiNH(2). The combination of NaMgH(3) with
      LiNH(2) at a molar ratio of 1 : 2 can release about 4.0 wt% of hydrogen without
      detectable NH(3) emission in the temperature range of 45  degrees C to 325 
      degrees C and exhibiting superior dehydrogenation as compared to individual NaH
      and/or MgH(2) combined with LiNH(2). A high capacity retention of about 75%
      resulting from the introduction of NaMgH(3) is also achieved in LiNH(2) as well
      as re-hydrogenation under milder conditions of 180  degrees C and 5 MPa H(2)
      pressure. These significant improvements are attributed to synergistic effects of
      in situ formed NaH and MgH(2)via the decomposition of NaMgH(3) where a succession
      of competing reactions from the cyclic consumption/recovery of NaH are involved
      and serve as a "carrier" for the ultra-rapid conveyance of the N-containing
      species between the [NH(2)](-) amide and the resulting [NH](2-) imide complexes.

PMID- 23165761
TI  - Vibrational spectroscopy and microscopic imaging: novel approaches for comparing
      barrier physical properties in native and human skin equivalents.
AB  - Vibrational spectroscopy and imaging have been used to compare barrier properties
      in human skin, porcine skin, and two human skin equivalents, Epiderm 200X with an
      enhanced barrier and Epiderm 200 with a normal barrier. Three structural
      characterizations were performed. First, chain packing and conformational order
      were compared in isolated human stratum corneum (SC), isolated porcine SC, and in
      the Epiderm 200X surface layers. The infrared (IR) spectrum of isolated human SC
      revealed a large proportion of orthorhombically packed lipid chains at
      physiological temperatures along with a thermotropic phase transition to a state
      with hexagonally packed chains. In contrast, the lipid phase at physiological
      temperatures in both porcine SC and in Epiderm 200X, although dominated by
      conformationally ordered chains, lacked significant levels of orthorhombic
      subcell packing. Second, confocal Raman imaging of cholesterol bands showed
      extensive formation of cholesterol-enriched pockets within the human skin
      equivalents (HSEs). Finally, IR imaging tracked lipid barrier dimensions as well
      as the spatial disposition of ordered lipids in human SC and Epiderm 200X. These
      approaches provide a useful set of experiments for exploring structural
      differences between excised human skin and HSEs, which in turn may provide a
      rationale for the functional differences observed among these preparations.

PMID- 23165762
TI  - Advanced chemical imaging and comparison of human and porcine hair follicles for
      drug delivery by confocal Raman microscopy.
AB  - Hair follicles have recently gained a lot of interest for dermal drug delivery.
      They provide facilitated penetration into the skin and a high potential to serve
      as a drug depot. In this area of research, excised pig ear is a widely accepted
      in vitro model to evaluate penetration of drug delivery into hair follicles.
      However, a comparison of human and porcine follicles in terms of chemical
      composition has not been performed so far. In this study, we applied confocal
      Raman microscopy as a chemically selective imaging technique to compare human and
      porcine follicle composition and to visualize component distribution within
      follicle cross-sections. Based on the evaluation of human and porcine Raman
      spectra optical similarity for both species was successfully confirmed.
      Furthermore, cyanoacrylate skin surface biopsies, which are generally used to
      determine the extent of follicular penetration, were imaged by a novel
      complementary analytical approach combining confocal Raman microscopy and optical
      profilometry. This all-encompassing analysis allows investigation of intactness
      and component distribution of the excised hair bulb in three dimensions. Confocal
      Raman microscopy shows a high potential as a noninvasive and chemically selective
      technique for the analysis of trans-follicular drug delivery.

PMID- 23165763
TI  - Fractionation of ethylcellulose oleogels during setting.
AB  - The use of ethylcellulose (EC) polymers as a means to structure edible oils for
      fat replacement is beginning to show great promise and the use of these
      'oleogels' has recently been shown to be feasible in food products. These gels
      are very versatile, as the mechanical properties can be tailored by altering
      either the fatty acid profile of the oil component, or the viscosity or
      concentration of the polymer component. Here we report the observation that
      certain formulation of EC oleogels tend to separate into two distinct phases; a
      soft interior core surrounded by a firm exterior sheath. It was found that the
      extent of this effect depends on EC viscosity, and can also be induced through
      the addition of certain surfactants, such as sorbitan monostearate and sorbitan
      monooleate, though not by glycerol monooleate. Although the two visually distinct
      regions were shown to be chemically indistinct, the cooling rate during gel
      setting was found to play a large role; rapid setting of the gels reduces the
      fractionation effect, while slow cooling produced a completely homogeneous
      structure. In addition, by reheating only the soft region of the gel, a firm and
      soft fractionated gel could again be produced. Finally, it was observed that
      oleogels prepared with castor oil or mineral oil have the ability to remove or
      induce the gel separation, respectively. Taken together, these results indicate
      chemical interactions may incite the separation into two distinct phases, but the
      process also seems to be driven by the cooling conditions during gel setting.
      These findings lend insight into the EC-oleogel gelation process and should
      provide a stepping stone for future research into the manufacturing of these
      products.

PMID- 23165764
TI  - Gating of the designed trimeric/tetrameric voltage-gated H+ channel.
AB  - The voltage-gated H(+) channel functions as a dimer, a configuration that is
      different from standard tetrameric voltage-gated channels. Each channel protomer
      has its own permeation pathway. The C-terminal coiled-coil domain has been shown
      to be necessary for both dimerization and cooperative gating in the two channel
      protomers. Here we report the gating cooperativity in trimeric and tetrameric Hv
      channels engineered by altering the hydrophobic core sequence of the coiled-coil
      assembly domain. Trimeric and tetrameric channels exhibited more rapid and less
      sigmoidal kinetics of activation of H(+) permeation than dimeric channels,
      suggesting that some channel protomers in trimers and tetramers failed to produce
      gating cooperativity observed in wild-type dimers. Multimerization of trimer and
      tetramer channels were confirmed by the biochemical analysis of proteins,
      including crystallography. These findings indicate that the voltage-gated H(+)
      channel is optimally designed as a dimeric channel on a solid foundation of the
      sequence pattern of the coiled-coil core, with efficient cooperative gating that
      ensures sustained and steep voltage-dependent H(+) conductance in blood cells.

PMID- 23165765
TI  - Cardiac-locked bursts of muscle sympathetic nerve activity are absent in familial
      dysautonomia.
AB  - Familial dysautonomia (Riley-Day syndrome) is an hereditary sensory and autonomic
      neuropathy (HSAN type III), expressed at birth, that is associated with reduced
      pain and temperature sensibilities and absent baroreflexes, causing orthostatic
      hypotension as well as labile blood pressure that increases markedly during
      emotional excitement. Given the apparent absence of functional baroreceptor
      afferents, we tested the hypothesis that the normal cardiac-locked bursts of
      muscle sympathetic nerve activity (MSNA) are absent in patients with familial
      dysautonomia. Tungsten microelectrodes were inserted percutaneously into muscle
      or cutaneous fascicles of the common peroneal nerve in 12 patients with familial
      dysautonomia. Spontaneous bursts of MSNA were absent in all patients, but in five
      patients we found evidence of tonically firing sympathetic neurones, with no
      cardiac rhythmicity, that increased their spontaneous discharge during emotional
      arousal but not during a manoeuvre that unloads the baroreceptors. Conversely,
      skin sympathetic nerve activity (SSNA), recorded in four patients, appeared
      normal. We conclude that the loss of phasic bursts of MSNA and the loss of
      baroreflex modulation of muscle vasoconstrictor drive contributes to the poor
      control of blood pressure in familial dysautonomia, and that the increase in
      tonic firing of muscle vasoconstrictor neurones contributes to the increase in
      blood pressure during emotional excitement.

PMID- 23165766
TI  - Reverse myocardial effects of intermedin in pressure-overloaded hearts: role of
      endothelial nitric oxide synthase activity.
AB  - Intermedin (IMD) is a cardiac peptide synthesized in a prepro form, which
      undergoes a series of proteolytic cleavages and amidations to yield the active
      forms of 47 (IMD(1-47)) and 40 amino acids (IMD(8-47)). There are several lines
      of evidence of increased IMD expression in rat models of cardiac pathologies,
      including congestive heart failure and ischaemia; however, its myocardial effects
      upon cardiac disease remain unexplored. With this in mind, we investigated the
      direct effects of increasing concentrations of IMD(1-47) (10(-10) to10(-6) m) on
      contraction and relaxation of left ventricular (LV) papillary muscles from two
      rat models of chronic pressure overload, one induced by transverse aortic
      constriction (TAC), the other by nitric oxide (NO) deficiency due to chronic NO
      synthase inhibition (NG-nitro-l-arginine, l-NAME), and respective controls (Sham
      and Ctrl). In TAC and l-NAME rats, exogenous administration of IMD(1-47) elicited
      concentration-dependent positive inotropic and lusitropic effects. By contrast,
      in Sham and Ctrl rats, IMD(1-47) induced a negative inotropic response without a
      significant effect on relaxation. Both TAC and l-NAME rats presented LV
      hypertrophy, elevated LV systolic pressures, preserved systolic function and
      elevated peroxynitrite levels. In the normal myocardium (Ctrl and Sham), IMD(1
      47) induced a 3-fold increase of endothelial nitric oxide synthase (eNOS)
      phosphorylation at Ser(1177), indicating enhanced eNOS activity. In TAC and l
      NAME rats, eNOS phosphorylation was increased at baseline, and its response to
      IMD(1-47) was blunted. In addition, the distinct myocardial response to IMD(1-47)
      was accompanied by distinct subcellular mechanisms. While in Sham rats the
      addition of IMD(1-47) induced the phosphorylation of cardiac troponin I due to
      NO/cGMP activation, in TAC rats IMD(1-47) induced phospholamban phosphorylation
      possibly associated with cAMP/protein kinase A activation. Therefore, we
      demonstrated for the first time a reversed myocardial response to IMD(1-47)
      neurohumoral stimulation due to impairment of eNOS activation in TAC and l-NAME
      rats. These results not only reveal the distinct myocardial effects and
      subcellular mechanisms for IMD(1-47) in normal and hypertrophic hearts, but also
      highlight the potential pathophysiological relevance of cardiac endothelial
      dysfunction in neurohumoral myocardial action.

PMID- 23165767
TI  - CLC-3 chloride channels moderate long-term potentiation at Schaffer collateral
      CA1 synapses.
AB  - The chloride channel CLC-3 is expressed in the brain on synaptic vesicles and
      postsynaptic membranes. Although CLC-3 is broadly expressed throughout the brain,
      the CLC-3 knockout mouse shows complete, selective postnatal neurodegeneration of
      the hippocampus, suggesting a crucial role for the channel in maintaining normal
      brain function. CLC-3 channels are functionally linked to NMDA receptors in the
      hippocampus; NMDA receptor-dependent Ca(2+) entry, activation of
      Ca(2+)/calmodulin kinase II and subsequent gating of CLC-3 link the channels via
      a Ca(2+)-mediated feedback loop. We demonstrate that loss of CLC-3 at mature
      synapses increases long-term potentiation from 135 +/- 4% in the wild-type slice
      preparation to 154 +/- 7% above baseline (P < 0.001) in the knockout; therefore,
      the contribution of CLC-3 is to reduce synaptic potentiation by ~40%. Using a
      decoy peptide representing the Ca(2+)/calmodulin kinase II phosphorylation site
      on CLC-3, we show that phosphorylation of CLC-3 is required for its regulatory
      function in long-term potentiation. CLC-3 is also expressed on synaptic vesicles;
      however, our data suggest functionally separable pre- and postsynaptic roles.
      Thus, CLC-3 confers Cl(-) sensitivity to excitatory synapses, controls the
      magnitude of long-term potentiation and may provide a protective limit on Ca(2+)
      influx.

PMID- 23165768
TI  - On-off asymmetries in oxygen consumption kinetics of single Xenopus laevis
      skeletal muscle fibres suggest higher-order control.
AB  - The mechanisms controlling skeletal muscle oxygen consumption (V(o)2) during
      exercise are not well understood. We determined whether first-order control could
      explain V(o)2kinetics at contractions onset (V(o)2(on)) and cessation (V(o)2off))
      in single skeletal muscle fibres differing in oxdidative capacity, and across
      stimulation intensities up to V(o)2(max). Xenopus laevis fibres (n = 21) were
      suspended in a sealed chamber with a fast response P(o)2 electrode to measure
      V(o)2 every second before, during and after stimulated isometric contractions. A
      first-order model did not well characterize on-transient V(o)2 kinetics.
      Including a time delay (TD) in the model provided a significantly improved
      characterization than a first-order fit without TD (F-ratio; P < 0.05), and
      revealed separate 'activation' and 'exponential' phases in 15/21 fibres
      contracting at V(o)2(max) (mean +/- SD TD: 14 +/- 3s). On-transient kinetics
      (tauV(o)2(on)) was weakly and linearly related to V(o)2(max) (R2 = 0.271, P =
      0.015). Off-transient kinetics, however, were first-order, and tauV(o)2(off) was
      greater in low-oxidative (V(o)2max < 0.05 nmol mm-3s-1 than high-oxidative fibres
      (V(o)2(max > 0.10 nmol mm -3 s-1; 170 +/- 70 vs. 29 +/- 6 s, P < 0.001). 1/
      tauV(o)2(off) was proportional to V(o)2(max) (R2 = 0.727, P < 0.001), unlike in
      the on-transient. The calculated oxygen deficit was larger (P < 0.05) than the
      post-contraction volume of consumed oxygen at all intensities except V(o)2(max).
      These data show a clear dissociation between the kinetic control of V(o)2at the
      onset and cessation of contractions and across stimulation intensities. More
      complex models are therefore required to understand the activation of
      mitochondrial respiration in skeletal muscle at the start of exercise.

PMID- 23165769
TI  - Mammalian target of rapamycin signalling modulates amino acid uptake by
      regulating transporter cell surface abundance in primary human trophoblast cells.
AB  - Abnormal fetal growth increases the risk for perinatal complications and
      predisposes for the development of obesity, diabetes and cardiovascular disease
      later in life. Emerging evidence suggests that changes in placental amino acid
      transport directly contribute to altered fetal growth. However, the molecular
      mechanisms regulating placental amino acid transport are largely unknown. Here we
      combined small interfering (si) RNA-mediated silencing approaches with protein
      expression/localization and functional studies in cultured primary human
      trophoblast cells to test the hypothesis that mammalian target of rapamycin
      complex 1 (mTORC1) and 2 (mTORC2) regulate amino acid transporters by post
      translational mechanisms. Silencing raptor (inhibits mTORC1) or rictor (inhibits
      mTORC2) markedly decreased basal System A and System L amino acid transport
      activity but had no effect on growth factor-stimulated amino acid uptake.
      Simultaneous inhibition of mTORC1 and 2 completely inhibited both basal and
      growth factor-stimulated amino acid transport activity. In contrast, mTOR
      inhibition had no effect on serotonin transport. mTORC1 or mTORC2 silencing
      markedly decreased the plasma membrane expression of specific System A (SNAT2,
      SLC38A2) and System L (LAT1, SLC7A5) transporter isoforms without affecting
      global protein expression. In conclusion, mTORC1 and mTORC2 regulate human
      trophoblast amino acid transporters by modulating the cell surface abundance of
      specific transporter isoforms. This is the first report showing regulation of
      amino acid transport by mTORC2. Because placental mTOR activity and amino acid
      transport are decreased in human intrauterine growth restriction our data are
      consistent with the possibility that dysregulation of placental mTOR plays an
      important role in the development of abnormal fetal growth.

PMID- 23165770
TI  - Responses of glomus cells to hypoxia and acidosis are uncoupled, reciprocal and
      linked to ASIC3 expression: selectivity of chemosensory transduction.
AB  - Carotid body glomus cells are the primary sites of chemotransduction of
      hypoxaemia and acidosis in peripheral arterial chemoreceptors. They exhibit
      pronounced morphological heterogeneity. A quantitative assessment of their
      functional capacity to differentiate between these two major chemical signals has
      remained undefined. We tested the hypothesis that there is a differential sensory
      transduction of hypoxia and acidosis at the level of glomus cells. We measured
      cytoplasmic Ca(2+) concentration in individual glomus cells, isolated in clusters
      from rat carotid bodies, in response to hypoxia ( mmHg) and to acidosis at pH
      6.8. More than two-thirds (68%) were sensitive to both hypoxia and acidosis, 19%
      were exclusively sensitive to hypoxia and 13% exclusively sensitive to acidosis.
      Those sensitive to both revealed significant preferential sensitivity to either
      hypoxia or to acidosis. This uncoupling and reciprocity was recapitulated in a
      mouse model by altering the expression of the acid-sensing ion channel 3 (ASIC3)
      which we had identified earlier in glomus cells. Increased expression of ASIC3 in
      transgenic mice increased pH sensitivity while reducing cyanide sensitivity.
      Conversely, deletion of ASIC3 in the knockout mouse reduced pH sensitivity while
      the relative sensitivity to cyanide or to hypoxia was increased. In this work, we
      quantify functional differences among glomus cells and show reciprocal
      sensitivity to acidosis and hypoxia in most glomus cells. We speculate that this
      selective chemotransduction of glomus cells by either stimulus may result in the
      activation of different afferents that are preferentially more sensitive to
      either hypoxia or acidosis, and thus may evoke different and more specific
      autonomic adjustments to either stimulus.

PMID- 23165771
TI  - Hyperpolarization of resting membrane potential causes retraction of spontaneous
      Ca(i)2+ transients during mouse embryonic circuit development.
AB  - Abstract  Spontaneous activity supports developmental processes in many brain
      regions during embryogenesis, and the spatial extent and frequency of the
      spontaneous activity are tightly regulated by stage. In the developing mouse
      hindbrain, spontaneous activity propagates widely and the waves can cover the
      entire hindbrain at E11.5. The activity then retracts to waves that are spatially
      restricted to the rostral midline at E13.5, before disappearing altogether by
      E15.5. However, the mechanism of retraction is unknown. We studied passive
      membrane properties of cells that are spatiotemporally relevant to the pattern of
      retraction in mouse embryonic hindbrain using whole-cell patch clamp and  
      imaging techniques. We find that membrane excitability progressively decreases
      due to hyperpolarization of resting membrane potential and increased resting
      conductance density between E11.5 and E15.5, in a spatiotemporal pattern
      correlated with the retraction sequence. Retraction can be acutely reversed by
      membrane depolarization at E15.5, and the induced events propagate similarly to
      spontaneous activity at earlier stages, though without involving gap junctional
      coupling. Manipulation of [K(+)](o) or [Cl(-)](o) reveals that membrane potential
      follows E(K) more closely than E(Cl), suggesting a dominant role for K(+)
      conductance in the membrane hyperpolarization. Reducing membrane excitability by
      hyperpolarization of the resting membrane potential and increasing resting
      conductance are effective mechanisms to desynchronize spontaneous activity in a
      spatiotemporal manner, while allowing information processing to occur at the
      synaptic and cellular level.

PMID- 23165772
TI  - Expanding role of ATP as a versatile messenger at carotid and aortic body
      chemoreceptors.
AB  - In mammals, peripheral arterial chemoreceptors monitor blood chemicals (e.g.
      O(2), CO(2), H(+), glucose) and maintain homeostasis via initiation of
      respiratory and cardiovascular reflexes. Whereas chemoreceptors in the carotid
      bodies (CBs), located bilaterally at the carotid bifurcation, control primarily
      respiratory functions, those in the more diffusely distributed aortic bodies
      (ABs) are thought to regulate mainly cardiovascular functions. Functionally, CBs
      sense partial pressure of O(2) ( ), whereas ABs are considered sensors of O(2)
      content. How these organs, with essentially a similar complement of chemoreceptor
      cells, differentially process these two different types of signals remains
      enigmatic. Here, we review evidence that implicates ATP as a central mediator
      during information processing in the CB. Recent data allow an integrative view
      concerning its interactions at purinergic P2X and P2Y receptors within the
      chemosensory complex that contains elements of a 'quadripartite synapse'. We also
      discuss recent studies on the cellular physiology of ABs located near the aortic
      arch, as well as immunohistochemical evidence suggesting the presence of pathways
      for P2X receptor signalling. Finally, we present a hypothetical 'quadripartite
      model' to explain how ATP, released from red blood cells during hypoxia, could
      contribute to the ability of ABs to sense O(2) content.

PMID- 23165773
TI  - The utility of serum tryptase as a marker in chronic spontaneous urticaria.

PMID- 23165774
TI  - Influence of surface topography and surface physicochemistry on wettability of
      zirconia (tetragonal zirconia polycrystal).
AB  - Surface modification technologies are available for tetragonal zirconia
      polycrystal (TZP) to enhance its bioactivity and osseointegration capability. The
      surface wettability of an implant material is one of the important factors in the
      process of osseointegration, possibly regulating protein adsorption, and
      subsequent cell behavior. The aim of this study was to clarify the effect of
      topographical or physicochemical modification of TZP ceramics on wettability to
      determine the potential of such treatment in application to implants. Several
      types of surface topography were produced by alumina blasting and acid etching
      with hydrofluoric acid; surface physicochemistry was modified with oxygen (O(2))
      plasma, ultraviolet (UV) light, or hydrogen peroxide treatment. The obtained
      specimens were also subjected to storage under various conditions to evaluate
      their potential to maintain superhydrophilicity. The results showed that surface
      modification of surface topography or physicochemistry, especially of blast/acid
      etching as well as O(2) plasma and UV treatment, greatly increased the surface
      wettability, resulting in superhydrophilicity. X-ray photoelectron spectroscopy
      revealed that a remarkable decrease in carbon content and the introduction of
      hydroxyl groups were responsible for the observed superhydrophilicity.
      Furthermore, superhydrophilicity was maintained, even after immersion in an
      aqueous solution, an important consideration in the clinical application of this
      technology.

PMID- 23165775
TI  - Effect of temperature and pH on postmortem color development of porcine M.
      longissimus dorsi and M. semimembranosus.
AB  - BACKGROUND: Purchasing pork that is boned within 1 h postmortem and not aged is
      customary in China, and final pork color would not be fully realized. The
      relationship between early postmortem, pre-rigor meat color and 24 h postmortem,
      post-rigor pork color was investigated and related to the rate of pH and
      temperature decline within the longissimus dorsi (LD) and the semimembranosus
      (SM) muscles of pork carcasses. Muscle color, pH and temperature were measured at
      45 min and at 3, 9, 15 and 24 h postmortem in carcasses of F2 White Duroc and
      Chinese Erhualian pigs. RESULTS: Pork color at 45 min postmortem was not
      indicative of that at 24 h postmortem in LD and SM, although muscle pH values and
      temperature at 45 min postmortem were significantly correlated with the LD and SM
      ultimate color. High muscle pH was associated with decreased L*, whereas high
      muscle temperature increased L*. Muscle pH and temperature had little effect on
      a* and b* in LD and color evolution in SM. CONCLUSIONS: Results indicated that
      meat color inspected shortly after slaughter does not reflect post-rigor meat
      quality.

PMID- 23165776
TI  - Immunocytochemical localization of the translocase of the outer mitochondrial
      membrane (Tom20) in the human cochlea.
AB  - Mitochondrial degeneration in the inner ear is likely a contributing factor in
      age-related hearing loss and other otopathologies such as Meniere's disease. Most
      mitochondrial proteins are synthesized in the cytosol and imported through the
      mitochondrial membranes by translocators. The translocase of the outer membrane
      (Tom) is the universal entry gate for all proteins that are imported into
      mitochondria. Altered function of the translocator could alter protein transport
      into the mitochondria, and disrupt function. In this study, we determined the
      immunolocalization of Tom20, a major mitochondrial protein import receptor, in
      microdissected human cochlea frozen sections obtained from postmortem autopsy and
      celloidin-embedded archival specimens. We used affinity purified rabbit
      polyclonal antibodies against Tom20. We also determined the Tom20
      immunolocalization in the mouse inner ear. In the human and mouse cochlea, Tom20
      was ubiquitously distributed in the organ of Corti, allowing well-delineated
      visualization of inner and outer hair cells. Tom20 immunoreactivity localized in
      the cytoplasm of spiral ganglia neurons. In the inner ear of aged subjects with
      Meniere's disease, there was decreased expression of Tom20. These results suggest
      that Tom20 can be used in the inner ear as a marker for mitochondrial protein
      import.

PMID- 23165777
TI  - Differential expression of IGF-1 mRNA isoforms in colorectal carcinoma and normal
      colon tissue.
AB  - The insulin-like growth factor (IGF)-1 gene consists of 6 exons resulting in the
      expression of 6 variant forms of mRNA (IA, IB, IC, IIA, IIB and IIC) due to an
      alternative splicing. The mechanisms of IGF-1 gene splicing and the role of local
      expression manifested by IGF-1 mRNA variants in colorectal carcinoma (CRC) have
      not been extensively investigated. Therefore, the aim of our study was to analyse
      the expression of IGF-1 mRNA isoforms [A, B, C, P1 (class I) and P2 (class II)],
      as well as the protein expression in CRC and control samples isolated from 28
      patients. The expression of Ki-67 was also analysed and clinical data were
      obtained. For this purpose, we used quantitative real-time PCR (qPCR) and
      immunocytochemistry. The expression of mRNAs coding for all splicing isoforms of
      IGF-1 was observed in every tissue sample studied, with a significantly lower
      expression noted in the CRC as compared to the control samples. The cytoplasmic
      expression of IGF-1 protein was found in 50% of the CRC and in ~40% of the non
      tumor tissues; however, no significant quantitative inter-group differences were
      observed. The expression of the IGF-1 gene in the 2 groups of tissues was
      controlled by the P1 and P2 promoters in a similar manner. No significant
      differences were detected in the expression of the IGF-1 A and B isoforms;
      however, their expression was significantly higher compared to that of isoform C.
      No significant differences were observed between the expression of Ki-67 mRNA in
      the CRC and control tissue even though the expression of the Ki-67 protein was
      higher in the CRC compared to the control samples. Ki-67 protein expression was
      associated with the macroscopic and microscopic aspects of CRC. A significant
      positive correlation was found between the local production of total mRNA and
      isoform A and the expression of Ki-67 mRNA, although only in the non-tumor
      tissues. In CRC samples, the local expression of the total IGF-1 mRNA and all
      splicing isoforms of IGF-1 mRNA decreased as compared to the normal colon
      tissues, although however, with conservation of both gene promoter activities and
      with the continued principal splicing IGF-1 mRNA isoforms.

PMID- 23165779
TI  - Simultaneous in vivo pH and temperature mapping using a PARACEST-MRI contrast
      agent.
AB  - Altered tissue temperature and/or pH is a common feature in pathological
      conditions, where metabolic demand exceeds oxygen supply such as in tumors and
      following stroke. Therefore, in vivo tissue temperature and pH may become
      valuable biomarkers for disease detection and the monitoring of disease
      progression or treatment response in conditions with altered metabolic demand. In
      this study, pH is measured using the amide protons of a thulium (Tm(3+)) complex
      with a DOTAM-Glycine-Lysine (ligand: Tm(3+)-DOTAM-Gly-Lys). The pH was uniquely
      determined from the linewidth of the asymmetry curve of the chemical exchange
      saturation transfer spectrum, independent of contrast agent concentration, or
      temperature for a given saturation pulse. pH maps with an inter-pixel standard
      deviation of less than 0.1 pH units were obtained in 10 mM Tm(3+)-DOTAM-Gly-Lys
      solutions with pH ranging from 6.0 to 8.0 pH units at 37 degrees C. Temperature
      maps were simultaneously obtained using the chemical shift of the chemical
      exchange saturation transfer peak. Temperature and pH maps are demonstrated in
      the mouse leg (N = 3), where the mean and standard deviation for pH was 7.2 +/-
      0.2 pH unit and temperature was 37.4 +/- 0.5 degrees C.

PMID- 23165778
TI  - Psychological factors predict local and referred experimental muscle pain: a
      cluster analysis in healthy adults.
AB  - BACKGROUND: Recent studies suggest an underlying three- or four-factor structure
      explains the conceptual overlap and distinctiveness of several negative
      emotionality and pain-related constructs. However, the validity of these latent
      factors for predicting pain has not been examined. METHODS: A cohort of 189 (99
      female, 90 male) healthy volunteers completed eight self-report negative
      emotionality and pain-related measures (Eysenck Personality Questionnaire -
      Revised, Positive and Negative Affect Schedule, State-Trait Anxiety Inventory,
      Pain Catastrophizing Scale, Fear of Pain Questionnaire; Somatosensory
      Amplification Scale, Anxiety Sensitivity Index and Whiteley Index). Using
      principal axis factoring, three primary latent factors were extracted: general
      distress, catastrophic thinking and pain-related fear. Using these factors,
      individuals clustered into three subgroups of high, moderate and low negative
      emotionality responses. Experimental pain was induced via intramuscular acidic
      infusion into the anterior tibialis muscle, producing local (infusion site)
      and/or referred (anterior ankle) pain and hyperalgesia. RESULTS: Pain outcomes
      differed between clusters (multivariate analysis of variance and multinomial
      regression), with individuals in the highest negative emotionality cluster
      reporting the greatest local pain (p = 0.05), mechanical hyperalgesia (pressure
      pain thresholds; p = 0.009) and greater odds (2.21 odds ratio) of experiencing
      referred pain when compared to the lowest negative emotionality cluster.
      CONCLUSION: Our results provide support for three latent psychological factors
      explaining the majority of the variance between several pain-related
      psychological measures, and that individuals in the high negative emotionality
      subgroup are at increased risk for (1) acute local muscle pain; (2) local
      hyperalgesia; and (3) referred pain using a standardized nociceptive input.

PMID- 23165780
TI  - Clinical and radiological features of Japanese patients with a severe phenotype
      due to CASK mutations.
AB  - Heterozygous loss of function mutations of CASK at Xp11.4 in females cause severe
      intellectual disability (ID) and microcephaly with pontine and cerebellar
      hypoplasia (MICPCH). However, the longitudinal clinical and radiological course
      of affected patients, including patterns of postnatal growth, has not been
      described. Neurodevelopmental and imaging information was retrospectively accrued
      for 16 Japanese (15 female and 1 male) patients with ID and MICPCH associated
      with CASK mutations. All records were analyzed; patient age ranged from 2 to 16
      years at the time of the most recent examinations. The growth pattern,
      neurological development, neurological signs/symptoms, and facial features were
      similar in the 15 female patients. Their head circumference at birth was within
      the normal range in about half, and their height and weight were frequently
      normal. This was followed by early development of severe microcephaly and
      postnatal growth retardation. The patients acquired head control almost normally
      between 3 and 6 months, followed by motor delay. More than half of the female
      patients had epilepsy. Their MRIs showed microcephaly, brainstem, and cerebellar
      hypoplasia in early infancy, and a normal or large appearing corpus callosum. The
      male patient showed a more severe clinical phenotype. These uniform clinical and
      radiological features should facilitate an early diagnosis and be useful for
      medical care of females with ID and MICPCH associated with CASK mutations.

PMID- 23165781
TI  - Neoadjuvant therapy with weekly docetaxel and cisplatin, 5-fluorouracil
      continuous infusion, and concurrent radiotherapy in patients with locally
      advanced esophageal cancer produced a high percentage of long-lasting
      pathological complete response: a phase 2 study.
AB  - BACKGROUND: This phase 2 study was aimed at defining the pathological response
      rate of a neoadjuvant schedule including weekly docetaxel and cisplatin,
      continuous infusion (c.i.) of 5-fluorouracil (5-FU) and concomitant radiotherapy
      (RT) in untreated stage II-III adenocarcinoma and squamous cell carcinoma of mid
      distal thoracic esophagus. METHODS: The schedule consisted of a first phase of
      chemotherapy alone and of a second phase of concurrent chemoradiation. Doses were
      as follows: docetaxel 35 mg/m(2) and cisplatin 25 mg/m(2) on days 1, 8, 15, 29,
      36, 43, 50, and 57 plus 5-FU c.i. (180 mg/m(2) on days 1-21 and 150 mg/m(2) on
      days 29-63); RT (50 Gy) started at day 29. Surgery was planned 6 to 8 weeks after
      the completion of chemoradiation. RESULTS: A total of 74 patients were enrolled;
      pathological complete remission (pCR) was found in 47% (35 of 74) and near pCR
      (microfoci of tumor cells on the primary tumor without lymph nodal metastases)
      (pnCR) in 15% of the patients (11 of 74). Grade 3-4 neutropenia, nonhematological
      toxicity, and toxic deaths occurred in 13.5%, 32.4%, and 4% of the patients,
      respectively. Median follow-up was 55 months (range, 3-108 months). Median
      survival of all 74 patients was 55 months, whereas it was not reached in the pCR
      subset. The 3- and 5-year survival rates were, respectively, 83% and 77% for pCR,
      73% and 44% for pnCR, and 21% and 14% for Residual Tumor subsets (P < .001).
      CONCLUSIONS: This study shows that 1) this intensive weekly schedule produced a
      high pathological response rate, 2) responders had high and long-term durable
      survival rates.

PMID- 23165782
TI  - Host response to intravenous injection of epsilon toxin in mouse model: a
      proteomic view.
AB  - Epsilon toxin (ETX) is an extremely potent pore-forming toxin and a category B
      biological agent. ETX is a major virulence determinant of Clostridium perfringens
      toxinotypes B and D, and is implicated in pathogenesis of rapidly fatal
      economically important pulpy kidney disease in lambs caused by toxinotype D.
      Despite being a toxin, ETX can be utilized as a tool to target glutamatergic
      neurons and for drug delivery into the CNS. 2DE-MS approach was employed to
      elucidate the host response to ETX following intravenous injection in mouse
      model. In total, 136 proteins were identified either differentially expressed in
      brain (18) and kidney (33); showing specific interaction with ETX from lysates of
      brain (4), kidney (21), or from plasma (42); and urine markers (18) of
      intoxication. Differentially expressed proteins in kidney included those involved
      in calcium homeostasis and cytoskeletal organization. Proteins involved in ER and
      oxidative stress and energy metabolism also showed differential levels in the
      target tissue after ETX treatment. The known functions of the proteins
      differentially expressed and those interacting with ETX indicate involvement of
      interlinked pathways. This study provides first proteomic account of host
      response to ETX exposure providing clues to mechanism of toxicity and potential
      therapeutic targets.

PMID- 23165783
TI  - Nonlinear amplification of a supramolecular complex at a multivalent interface.
AB  - Competition with a monovalent cyclodextrin host (blue cones) in solution drives
      the multivalent binding of a Eu(3+) complex and a sensitizer molecule to
      cyclodextrin monolayers through a nonlinear self-assembly process. Adamantyl
      groups (light-blue spheres) are attached to the EDTA ligand (black) and the
      antenna molecule (orange), which has a carboxylate group for coordination to the
      Eu(3+) ion (yellow or red in free or complexed form, respectively).

PMID- 23165784
TI  - 4,10-Dibromoanthanthrone as a new building block for p-type, n-type, and
      ambipolar pi-conjugated materials.
AB  - New p-type, n-type, and ambipolar molecules were synthesized from commercially
      available 4,10-dibromoanthanthrone dye. Substitution at the 4,10- and 6,12
      positions with different electron-rich and electron-poor units allowed the
      modulation of the optoelectronic properties of the molecules. A
      bis(dicyanovinylene)-functionalized compound was also prepared with a reduction
      potential as low as -50 mV versus Ag(+)  with a crystalline two-dimensional
      lamellar packing arrangement. These characteristics are important prerequisites
      for air-stable n-type organic field-effect transistor applications.

PMID- 23165785
TI  - Guidelines for Secondary Prevention of Myocardial Infarction (JCS 2011).

PMID- 23165786
TI  - Guidelines for Non-Pharmacotherapy of Cardiac Arrhythmias (JCS 2011).

PMID- 23165788
TI  - Effects of Maillard reaction on allergenicity of buckwheat allergen Fag t 3
      during thermal processing.
AB  - BACKGROUND: Fag t 3 is a major allergenic protein in tartary buckwheat. The
      Maillard reaction commonly occurs in food processing, but few studies have been
      conducted on the influence of thermal processing on the allergenic potential of
      buckwheat allergen. The aim of the present study was to investigate the effects
      of autologous plant polysaccharides on the immunoreactivity of buckwheat Fag t 3
      (11S globulin) following the Maillard reaction. RESULTS: Fag t 3 and crude
      polysaccharides were prepared from tartary buckwheat (Fagopyrum tataricum) flour.
      After heating, the polysaccharides were covalently linked to Fag t 3 via a
      Maillard reaction, and the IgE/IgG-binding properties of Fag t 3 decreased
      dramatically, with significant changes also being observed in the electrophoretic
      mobility, secondary structure and solubility of the glycated Fag t 3. The great
      influence of glycation on IgE/IgG binding to Fag t 3 was correlated with a
      significant change in the structure and epitopes of the allergenic protein. These
      data indicated that conjugation of polysaccharides to Fag t 3 markedly reduced
      the allergen's immunoreactivity. CONCLUSION: Glycation that occurs via the
      Maillard reaction during the processing of buckwheat food may be an efficient
      method to reduce Fag t 3 allergenicity.

PMID- 23165789
TI  - Contrast-enhanced ultrasonography in the diagnosis of upper urinary tract
      urothelial cell carcinoma: a preliminary study.
AB  - PURPOSE: The main objective was to assess the effectiveness of contrast-enhanced
      ultrasonography (CEUS) in the diagnosis of upper urinary tract malignancies by
      comparing with multidetector computed tomographic urography (MDCTU) and magnetic
      resonance urography (MRU). Secondary objectives were to compare the tumor size
      measured with CEUS, MDCTU and MRU and to assess the usefulness of CEUS in
      distinguishing high-grade tumors from low-grade ones. MATERIALS AND METHODS: In
      connection with this prospective study carried out from January 2009 to September
      2011, 18 patients underwent MDCTU or MRU, grayscale ultrasonography (US), color
      Doppler ultrasonography and CEUS followed by surgery and histological examination
      of the specimen. Quantitative analysis was performed using perfusion software.
      Time intensity curves were extracted and the following parameters were
      considered: wash-in time, time-to-peak, maximum signal intensity and wash-out
      time. RESULTS: Grayscale US identified 15/18 lesions; color Doppler showed no
      flow signal in 8 lesions, low color signal in 9 lesions and an intense color
      signal in 1 lesion; CEUS identified 17/18 lesions with the undetected lesion
      being the smallest one (1.2 cm) located in the upper pelvicalyceal system. Semi
      quantitative analysis produced different data for high-grade and low-grade
      urothelial cell carcinoma (UCC). All detected upper urinary tract masses were
      UCCs. MRU, MDCTU and grayscale US overestimated the tumor size, while CEUS was
      the most accurate. CONCLUSION: CEUS is useful for evaluating upper urinary tract
      masses as this method permits differentiation between high-grade and low-grade
      tumors as well as distinction of the tumor from the adjacent structures and
      accurate mass measurements.

PMID- 23165790
TI  - Reference values for testicular volume, epididymal head size and peak systolic
      velocity of the testicular artery in adult males measured by ultrasonography.
AB  - PURPOSE: To obtain ultrasonography-based reference values for testicular volume,
      epididymal head size and peak systolic velocity (PSV) of the testicular artery in
      adult males of all ages. MATERIALS AND METHODS: Between 2009 and 2011, 306
      Caucasian adult males (median age: 51 years; range: 18-88 years) without scrotal
      pathology underwent prospective scrotal ultrasonography. The testicular volume
      was calculated from the length (L), width (W), and height (H) using three
      formulas: a) 0.52 * L * W * H, b) 0.52 * L * W2, and c) 0.71 * L * W * H.
      Thickness and height of the epididymal head and PSV of the testicular artery were
      measured. RESULTS: The median testicular volumes on the right (left) side were
      13.9 (12.7) ml, 18.1 (16.5) ml, and 18.9 (17.3) ml for formula a), b), and c)
      respectively, and thus significantly different (p < 0.01 for all). The left
      testes were significantly smaller than the right testes (p < 0.01). The thickness
      and height of the right (left) epididymal head measured 7.5 (7.7) mm and 11.6
      (11.3) mm, respectively. Median PSV of the right (left) testicular artery was 8.7
      (8.6) cm/sec. No significant side-specific differences were documented with
      respect to epididymal size and PSV. CONCLUSION: It was possible to obtain
      virtually age-independent reference values for testicular volume, epididymal head
      size and PSV of the testicular artery in adults. With regard to testicular
      volumetry, it is essential to consider which formula has been used, since the
      calculated volumes differ significantly from formula to formula.

PMID- 23165791
TI  - Influence of cement stiffness and bone morphology on the compressive properties
      of bone-cement composites in simulated vertebroplasty.
AB  - Vertebroplasty is widely used to treat vertebral compression fractures. Little is
      known about the influence of morphological parameters of the bone on the
      properties of the bone-cement composite. Furthermore, although generic finite
      element (FE) models have been suggested as a way to compute the values of these
      properties, their accuracy has not been established. In the experimental part of
      this study, we tested bovine cancellous bone and three different
      polymethylmethacrylate bone cements and determined six quasi-static uniaxial
      compressive properties of bone-cement composite specimens and 10 morphological
      parameters of the bone. For the FE work, we used two simulations, one being MUFE
      and the other unit cell FE. In conclusion, we found that (1) for composite
      specimens, that relative contribution of the cement to the overall response of
      the composite increases with increasing cement stiffness; (2) the anisotropy
      ratio is the bone morphological property that exerts the most significant
      influence on the experimentally obtained compressive properties of the bone
      cement composites determined; (3) the accuracy of the computed compressive
      properties of the composites ranged from low to high, depending on simulation
      method used. The largest errors, however, can partially be explained by
      difference in boundary conditions between the experimental testing and the
      simulation techniques. The lattermost finding points to the potential for
      simplified FE models being incorporated into automatic material mapping schemes
      in whole bone vertebra FE simulations.

PMID- 23165792
TI  - Protective effects of Houttuynia cordata aqueous extract in mice consuming a high
      saturated fat diet.
AB  - The protective effects of Houttuynia cordata aqueous extract (HCAE) in mice
      consuming a high saturated fat diet (HFD) were examined. HCAE, at 0.5, 1, or 2%,
      was supplied in drinking water for 8 weeks. HCAE was rich in phenolic acids and
      flavonoids. HCAE intake at 1 and 2% decreased body weight, epididymal fat,
      insulin resistance, triglyceride and total cholesterol contents in plasma and
      liver from HFD-treated mice (p < 0.05). HFD enhanced hepatic activity of malic
      enzyme, fatty acid synthase (FAS) and 3-hydroxy-3-methylglutaryl coenzyme A
      reductase; and augmented the hepatic level of saturated fatty acids (p < 0.05).
      HCAE intake at 2% reduced malic enzyme and FAS activities, and lowered saturated
      fatty acids content in liver (p < 0.05). HCAE suppressed HFD induced oxidative
      and inflammatory stress in the heart and liver via reducing the malondialdehyde
      level, retaining glutathione content and glutathione peroxidase activity,
      decreasing tumor necrosis factor-alpha, interleukin (IL)-1beta and IL-6
      production (p < 0.05). These results support that Houttuynia cordata is a potent
      food against HFD induced obesity, and oxidative and inflammatory injury.

PMID- 23165793
TI  - The presence of two different target-site resistance mechanisms in individual
      plants of Alopecurus myosuroides Huds., identified using a quick molecular test
      for the characterisation of six ALS and seven ACCase SNPs.
AB  - BACKGROUND: Target-site resistance to ALS- and ACCase-inhibiting herbicides in
      the grass weed Alopecurus myosuroides is associated with well-characterised
      allelic variants encoding ALS- and ACCase-based resistance. The potential for
      combined ALS and ACCase resistance presents a threat to future control, given the
      extent to which these herbicides are used. The authors present a primer extension
      method for rapid detection of known resistance-conferring substitutions. RESULTS:
      Individuals showing combined resistance to field-rate mesosulfuron + iodosulfuron
      and cycloxydim were identified in four field-collected populations, with
      proportions ranging from 30 to 100%. Genotyping with the SNaPshot primer
      extension kit showed the T197 and L574 ALS and L1781 ACCase isoforms to be
      associated with ALS and ACCase resistance whenever they occurred. CONCLUSION:
      Combined ALS and ACCase target-site resistance threatens future control of A.
      myosuroides. The SNaPshot extension assay provides a reliable new multiplexable
      method for characterising known allelic variants of the ALS and ACCase genes of
      A. myosuroides. The method offers significant advantages over both CAPS/dCAPS and
      PASA in that full genotyping can be accomplished at any nucleotide position using
      a single extension primer.

PMID- 23165794
TI  - Ulcerated nodules on the oral mucosa and fingers: lymphomatoid papulosis, type A.

PMID- 23165795
TI  - Neuroimaging and neurological findings in patients with hypochondroplasia and
      FGFR3 N540K mutation.
AB  - Hypochondroplasia (HCH), an autosomal dominant skeletal dysplasia caused by
      mutations in the FGFR3 gene, has not been commonly associated with neurological
      problems. Temporal lobe dysgenesis associated with epilepsy was recently
      described in single patients. In this retrospective study, we assessed
      neurological and neuroimaging aspects of 13 FGFR3 (N540K) mutation verified HCH
      patients in Finland. Eight patients had neurocognitive difficulties, ranging from
      specific learning disorder (2/13) to mild intellectual disability (5/13) or
      global developmental delay (1/13). Six of 13 patients had a history of seizures
      or epilepsy. Eight patients had undergone MRI. They all had structural
      abnormalities consistent with temporal lobe dysgenesis. Six patients had
      peritrigonal white matter reduction, and 4 had abnormally shaped lateral
      ventricles. We recommend a close follow-up of development in patients with HCH
      and a low threshold for neuroimaging.

PMID- 23165796
TI  - T2 relaxometry with indirect echo compensation from highly undersampled data.
AB  - PURPOSE: To develop an algorithm for fast and accurate T2 estimation from highly
      undersampled multi-echo spin-echo data. METHODS: The algorithm combines a model
      based reconstruction with a signal decay based on the slice-resolved extended
      phase graph (SEPG) model with the goal of reconstructing T2 maps from highly
      undersampled radial multi-echo spin-echo data with indirect echo compensation. To
      avoid problems associated with the nonlinearity of the SEPG model, principal
      component decomposition is used to linearize the signal model. The proposed CUrve
      Reconstruction via principal component-based Linearization with Indirect Echo
      compensation (CURLIE) algorithm is used to estimate T2 curves from highly
      undersampled data. T2 maps are obtained by fitting the curves to the SEPG model.
      RESULTS: Results on phantoms showed T2 biases (1.9% to 18.4%) when indirect
      echoes are not taken into account. The T2 biases were reduced (< 3.2%) when the
      CURLIE reconstruction was performed along with SEPG fitting even for high degrees
      of undersampling (4% sampled). Experiments in vivo for brain, liver, and heart
      followed the same trend as the phantoms. CONCLUSION: The CURLIE reconstruction
      combined with SEPG fitting enables accurate T2 estimation from highly
      undersampled multi-echo spin-echo radial data thus, yielding a fast T2 mapping
      method without errors caused by indirect echoes.

PMID- 23165797
TI  - Correlation of TP53 and MDM2 genotypes with response to therapy in sarcoma.
AB  - BACKGROUND: Relatively few sarcomas harbor TP53 (tumor protein p53) mutations,
      but in many cases, amplification of MDM2 (murine double minute 2) effectively
      inactivate p53. The p53 pathway activity can also be affected by normal genetic
      variation. METHODS: The mutation status of TP53 and expression of MDM2, TP53, and
      their genetic variants SNP309 and R72P (Arg72Pro) were investigated in 125
      sarcoma patient samples and 18 sarcoma cell lines. Association of the different
      genotypes and gene aberrations with chemotherapy response and survival, as well
      as response to MDM2 antagonists in vitro was evaluated. RESULTS: Twenty-two
      percent of the tumors had mutant TP53 and 20% MDM2 gene amplification. Patients
      with wild-type TP53 (TP53(Wt) ) tumors had improved survival (P < .001) and
      TP53(Wt) was an independent prognostic factor (hazard ratio = 0.41; 95%
      confidence interval = 0.23-0.74; P = .03). Interestingly, there was a trend
      toward longer time to progression after chemotherapy for tumors with the
      apoptosis-prone p53 variant R72 (P = .07), which was strongest with
      doxorubicin/ifosfamide-based regimens (P = .01). Liposarcomas had low R72
      frequency (33% versus 56%), but increased levels of MDM2 and MDM4 (51% and 11%, P
      < .001). MDM2 overexpression on a TP53(Wt) background predicted better response
      to MDM2 antagonist Nutlin-3a, irrespective of R72P or SNP309 status. CONCLUSIONS:
      Improved survival after chemotherapy was found in patients with TP53(Wt) tumors
      harboring the R72 variant. MDM2 overexpression in TP53(Wt) tumors predicted good
      response to MDM2 antagonists, irrespective of R72P or SNP309 status. Thus,
      detailed TP53 and MDM2 genotype analyses prior to systemic therapy are
      recommended.

PMID- 23165798
TI  - Drug-induced gynecomastia.
AB  - Drugs account for about 20% of gynecomastia cases in men. As a number of factors
      can alter the estrogen:androgen ratio, several pathophysiologic mechanisms are
      associated with drugs causing this disorder. Antiandrogens, protease inhibitors,
      and nucleoside reverse transcriptase inhibitors are the most common drug causes
      of gynecomastia, whereas first-generation antipsychotics, spironolactone,
      verapamil, and cimetidine are less common causes. Other drugs have been reported
      rarely as causes. Treatment may involve switching to an alternative agent or may
      require surgery or irradiation if the causative agent cannot be discontinued. We
      reviewed the literature on drug-induced gynecomastia and provided another
      perspective by reviewing data from the United States Food and Drug
      Administration's Adverse Event Reporting System. Epidemiologic studies are needed
      to provide a more accurate description of the frequency of drug-induced
      gynecomastia.

PMID- 23165799
TI  - Course and risk factors of functional impairment in subthreshold depression and
      anxiety.
AB  - BACKGROUND: Although persons with subthreshold depression or anxiety are known to
      be at risk for full-syndromal disorders, little is known about their functioning
      over time. In this study, we investigate the functional impairment of persons
      with subthreshold depression or anxiety over time, compared to that of controls.
      Furthermore, we evaluate which illness, personal, and environmental risk factors
      influence its course. METHODS: Data come from the Netherlands Study of Depression
      and Anxiety (N = 1,266, aged 18-65). Linear mixed models were used to identify
      predictors of functional impairment at baseline, 1-, and 2-year follow-up. Risk
      factors were evaluated in their overall effect on functioning and on change in
      functioning over time, and whether they differed for respondents with and without
      subthreshold depression or anxiety. RESULTS: Functional impairment in
      subthreshold respondents improved over time, but remained much higher than in
      controls. Prior anxiety disorder, high neuroticism, low conscientiousness, more
      somatic conditions, and more childhood trauma all predicted greater functional
      impairment. Older age predicted lower functioning only in subthreshold
      respondents, while the effect of neuroticism was stronger in subthreshold
      respondents relative to controls. CONCLUSIONS: Functional impairment in
      subthreshold respondents improved over time, but remained elevated compared to
      that of controls. Given continuously elevated levels of impairment, preventive
      interventions should be focused on persons with subthreshold symptoms; in
      particular those with prior anxiety disorder, high neuroticism, low
      conscientiousness, somatic conditions, or childhood trauma.

PMID- 23165800
TI  - Development of mucoadhesive drug delivery system using phenylboronic acid
      functionalized poly(D,L-lactide)-b-dextran nanoparticles.
AB  - Mucoadhesive NP drug carriers have attracted substantial interest as a potential
      treatment for anterior eye diseases. NPs composed of PLA-Dex surface
      functionalized with a mucoadhesive ligand, PBA, were developed as drug carriers
      with particle sizes ranging from 25 to 28 nm. Using CycA as a model drug, we
      showed that NPs encapsulated up to 13.7 wt% CycA and exhibited sustained release
      for up to 5 d in vitro at a clinically relevant dose. We fine-tuned the PBA
      density on the NP surface to maximize the mucin-NP interaction without
      compromising the particle stability in vitro. This block copolymer conjugate may
      be useful to improve the bioavailability of topical formulations.

PMID- 23165802
TI  - Role of big mitogen-activated protein kinase 1 (BMK1) / extracellular signal
      regulated kinase 5 (ERK5) in the pathogenesis and progression of atherosclerosis.
AB  - Big mitogen-activated protein kinase 1 (BMK1), also known as extracellular signal
      regulated kinase 5 (ERK5), is a newly identified member of the mitogen-activated
      protein (MAP) kinase family. BMK1 has been reported to be sensitive to various
      neuro-humoral factors and oxidative stress in various cells. In this review, we
      focused on the role of BMK1 in atherosclerosis in a cultured rat aortic smooth
      muscle cell model. Treatment with platelet-derived growth factor caused vascular
      smooth muscle cell (VSMC) migration in a BMK1 activation-dependent manner.
      H(2)O(2) caused BMK1 activation and VSMC death, including apoptosis of VSMCs. An
      inhibitory function for BMK1 against cell death from oxidative stress was
      discovered using siRNA techniques to downregulate the expression of BMK1. These
      findings suggest a role for BMK1 in the pathogenesis and/or progression of
      atherosclerosis.

PMID- 23165803
TI  - Endocytic regulation of voltage-dependent potassium channels in the heart.
AB  - Understanding the regulation of cardiac ion channels is critical for the
      prevention of arrhythmia caused by abnormal excitability. Ion channels can be
      regulated by a change in function (qualitative) and a change in number
      (quantitative). Functional changes have been extensively investigated for many
      ion channels including cardiac voltage-dependent potassium channels. By contrast,
      the regulation of ion channel numbers has not been widely examined, particularly
      with respect to acute modulation of ion channels. This article briefly summarizes
      stimulus-induced endocytic regulation of major voltage-dependent potassium
      channels in the heart. The stimuli known to cause their endocytosis include
      receptor activation, drugs, and low extracellular [K(+)], following which the
      potassium channels undergo either clathrin-mediated or caveolin-mediated
      endocytosis. Receptor-mediated endocytic regulation has been demonstrated for
      Kv1.2, Kv1.5, KCNQ1 (Kv7.1), and Kv4.3, while drug-induced endocytosis has been
      demonstrated for Kv1.5 and hERG. Low [K(+)](o)-induced endocytosis might be
      unique for hERG channels, whose electrophysiological characteristics are known to
      be under strong influence of [K(+)](o). Although the precise mechanisms have not
      been elucidated, it is obvious that major cardiac voltage-dependent potassium
      channels are modulated by endocytosis, which leads to changes in cardiac
      excitability.

PMID- 23165804
TI  - Recombinant human brain natriuretic peptide therapy combined with bone
      mesenchymal stem cell transplantation for treating heart failure in rats.
AB  - This study aimed to investigate the effects of combined recombinant human brain
      natriuretic peptide (rhBNP) therapy and bone mesenchymal stem cell (BMSC)
      transplantation on cell survival in myocardial tissues and on heart function in a
      rat model of heart failure (HF). Rat BMSCs were isolated, amplified and adherent
      cultured in vitro. A rat model of HF was established via the intraperitoneal
      injection of doxorubicin (Adriamycin). The rats were randomly divided into
      normal, HF, BMSC, rhBNP and BMSC plus rhBNP groups. The BMSCs were administered
      once via tail vein injection and rhBNP was infused via the jugular vein.
      Echocardiography and polygraphy were used to evaluate heart function. An enzyme
      linked immunosorbent assay was used to detect the changes in brain natriuretic
      peptide (BNP) concentration prior to and following intervention. Western blot
      analysis was used to detect the expression of the myocardium-specific proteins
      GATA-binding protein 4 (GATA-4), connexin 43 (Cx43) and cardiac troponin I
      (cTnI). The results of cardiac echocardiography and the hemodynamic data show
      that various indicators of left ventricular systolic function in the BMSC plus
      rhBNP group were significantly improved compared with those in the other groups
      (P<0.05). No significant differences in the improvement of cardiac function were
      observed between the BMSC and rhBNP groups (P>0.05). Following treatment, a
      significant difference in BNP levels was observed between the BMSC plus rhBNP and
      the BMSC groups (P<0.05). The GATA-4, Cx43 and cTnI expression levels in the BMSC
      plus rhBNP group were higher than those in the BMSC group. Compared with rhBNP
      treatment, BMSC transplantation alone does not significantly improve heart
      function. However, combining rhBNP therapy and BMSC transplantation increases the
      expression levels of GATA-4 and other proteins to improve cardiac systolic and
      diastolic function.

PMID- 23165805
TI  - Synthetic and computational study of geminally bis(supermesityl) substituted
      phosphorus compounds.
AB  - Reaction chemistry of an extremely sterically encumbered phosphinic chloride
      (Mes*)(2)P(=O)Cl (Mes* = 2,4,6-tri-t-butylphenyl, supermesityl) was investigated.
      This compound, as well as other compounds bearing two supermesityl groups placed
      geminally at the central phosphorus atom, shows extremely low reactivity at the
      phosphorus centre. Nevertheless, some synthetically significant transformations
      were possible. Reduction with hydridic reagents under forcing conditions yielded
      the phosphine oxide (Mes*)(2)P(=O)H and a secondary phosphine Mes*(2,4
      tBu(2)C(6)H(3))PH. Deprotonation of (Mes*)(2)P(=O)H gave the corresponding
      phosphinite, which afforded very crowded tertiary phosphine oxides
      (Mes*)(2)P(=O)R (R = Me and Et) on reactions with electrophiles. While the
      reaction of the phosphine Mes*(2,4-tBu(2)C(6)H(3))PH with sulfur was surprisingly
      facile (although under forcing conditions), we have been unable to chlorinate or
      deprotonate this phosphine. All new compounds were fully characterised with
      multinuclear NMR, IR, Raman, MS, microanalyses and single crystal X-ray
      diffraction. Our computations (B3LYP and M06-2X level) show that strain energies
      of (synthetically accessible) geminally substituted compounds are extremely high
      (180 to 250 kJ mol(-1)), the majority of the strain is stored as boat distortions
      to the phenyl rings in Mes* substituents.

PMID- 23165806
TI  - Effect of topical application of silymarin (Silybum marianum) on excision wound
      healing in albino rats.
AB  - Silymarin, an extract from Silybum marianum, has been shown to have antioxidant
      properties. However, there is no scientific report on wound healing activity of
      the silymarin. The purpose of this study was to evaluate the effect of topical
      administration of silymarin on excision wound healing in rats. Excision wounds
      were made on the back of rats. Rats were divided into three groups, as control,
      vehicle, and treatment. Vehicle and treatment groups received polyethylene glycol
      and silymarin dissolved in polyethylene glycol, respectively. The control group
      did not receive any treatment. The wound tissues were removed on 5th, 10th and
      15th day for histopathological analysis and total collagen determination by
      hydroxyproline assay. Results showed that silymarin increased epithelialization
      and decreased inflammation but did not have any effect on percentage of wound
      contraction, collagenization and hydroxyproline levels. It was concluded that
      silymarin can significantly stimulate epithelialization and reduce inflammation
      in full-thickness wounds in rats.

PMID- 23165807
TI  - Effect of aqueous extract of Elaeagnus angustifolia fruit on experimental
      cutaneous wound healing in rats.
AB  - The present study was conducted to investigate the histological changes and wound
      healing effect of aqueous extract of Elaeagnus angustifolia. After creating full
      thickness skin wounds on the back of 45 male Sprague-Dawley rats they were
      randomly divided into three groups. Treated group received the extract, positive
      control group were treated with mupirocin ointment 2% and control group did not
      receive any treatment. Wound healing rates were calculated on days 3, 5, 8, 10,
      12 and 15 post-wounding and the wound tissues were harvested at 5, 10, and 15
      days for histological analysis and hydroxyproline content measurement. The
      results indicated a significant increase in the percentage of wound contraction
      and hydroxyproline content in the treated group comparing to the control and
      positive control groups. A significant increase in the assigned histological
      scores was observed at 10 and 15 days in the treated and positive control groups
      compared to the control group. The results demonstrate that aqueous extract of
      Elaeagnus angustifolia accelerates cutaneous wound healing, and its effect may be
      due to the increased re-epithelialization and collagen deposition in wound and so
      it can be considered as a therapeutic agent for wound healing.

PMID- 23165808
TI  - Novel biochemical markers: early detection and prevention of malignant
      transformation a pilot study.
AB  - The role of oxygen free radicals in the initiation, promotion and progression of
      carcinogenesis and the protective role of anti-oxidant defenses has been the
      subject of much speculation in the recent past with conflicting reports in the
      literature. In recent years, increasing experimental and clinical data have
      provided compelling evidence for the involvement of oxidative stress in a large
      number of pathological states including cancers. The aim of this study was to
      measure the concentration of serum total proteins and albumin as potent anti
      oxidants in the sera of patients diagnosed with speckled leukoplakia, one of the
      oral pre-cancerous lesions reported to have significantly high malignant
      transformation rates and well-differentiated oral squamous cell carcinoma. The
      study consisted of sera analysis of total protein and albumin levels in patients
      with speckled leukoplakia and histologically proven, well-differentiated oral
      squamous cell carcinoma. One way analyses of variance (ANOVA) was used to test
      the difference between groups. To find out which of the two groups' means were
      significantly different; post-hoc test of Scheffe was used. The study revealed
      variations in sera levels of albumin to be statistically significant. The results
      obtained emphasize the need for more studies with larger sample sizes to be
      conducted before a conclusive role for sera levels of total protein and albumin
      could be drawn as markers of transition from the various oral pre-cancerous
      lesions and conditions to frank oral squamous cell carcinoma.

PMID- 23165809
TI  - Clinical, high resolution computed tomography and pulmonary function in sulphur
      mustard victims.
AB  - We aimed to evaluate clinical, high resolution computed tomography (HRCT) and
      pulmonary function test (PFT) findings after 18-23 years of exposure in veterans
      of sulphur mustard (SM) exposure. We performed a cross-sectional study of 106
      patients. Inclusion criteria were 1: documented exposure to SM as confirmed by
      toxicological analysis of their urine and vesicular fluid after exposure 2:
      single exposure to SM that cause skin blisters and subsequent transient or
      permanent sequel. Cigarette smoking and pre-exposure lung diseases were of
      exclusion criteria. After taking history and thorough respiratory examination,
      patients underwent high resolution computed tomography and spirometry. Clinical
      diagnoses were made considering the findings. More than 85% of the patients were
      complaining of dyspnea and cough. Obstructive pattern (56.6%) was main finding in
      spirometry followed by restrictive and normal patterns. HRCT revealed air
      trapping (65.09%) and mosaic parenchymal attenuation patterns (58.49%) as most
      common results. Established diagnoses mainly were chronic obstructive pulmonary
      disease (COPD) (54.71%), bronchiolitis obliterans (27.35%) and asthmatic
      bronchitis (8.49%). There were not any significant association between the
      clinical findings and results of PFT and HRCT imaging and also between PFT and
      HRCT findings (P-values were more than 0.05). Considering debilitating and
      progressive nature of the respiratory complications of SM exposure, attempts are
      needed for appropriate diagnosis and treatment.

PMID- 23165810
TI  - Comparison of effects of ephedrine, lidocaine and ketamine with placebo on
      injection pain, hypotension and bradycardia due to propofol injection: a
      randomized placebo controlled clinical trial.
AB  - Propofol is a widely used anesthetic drug because of its minor complication and
      also its fast effect. One of most popular complication in using this drug is pain
      during injection that is more sever in new generation of its components (lipid
      free microemulsion). Other complications of propofol are bradycardia and
      hypotension. This study compares 3 drugs with placebo in control of these
      complications of propofol. In this double blinded randomized placebo controlled
      trial 140 patient who were candidates for elective surgery were divided in 4
      groups (35 patients in each groups) and drugs (ephedrine, lidocaine, ketamine and
      NaCl solution (as placebo) were tried on each group by a blinded technician and
      responses to drugs were evaluated under supervision of a blinded
      anesthesiologist. Pain after injection, systolic blood pressure (SBP), diastolic
      blood pressure (DBP), mean arterial pressure (MAP) and heart rate (HR) were
      measured 5 times during anesthesia process of each patient. All gathered data
      were analyzed using t-test and Chi-square under SPSS software. Our data shows
      that in pain management all tested drugs can decrease pain significantly
      comparing with placebo (P=0.017). In control of hemodynamic parameters ephedrine
      could efficiently control SBP, DBP, MAP at the time 1 min after intubation. Based
      on our study ephedrine can be an appropriate suggestion for control of both pain
      and hemodynamic changes induced by propofol, although because of inconsistent
      result in other studies it is recommended to design a systematic review to draw a
      broader view on this issue.

PMID- 23165811
TI  - Effect of preoperative anemia on short term clinical outcomes in diabetic
      patients after elective off-pump CABG surgery.
AB  - Diabetic mellitus (DM) is a major risk factor of morbidity, mortality and
      economic cost to society. Diabetic patients are at risk of having microvascular
      or macrovascular disorders of diabetes. Postoperative anemia have wide spectrum
      of some early complications that require more care in hospitalization stays.
      Therefore, this study was designed to evaluate effect of preoperative anemia on
      short-term clinical outcomes in diabetic patients undergoing elective off-pump
      CABG. This study conducted on 86 diabetic patients underwent elective off-pump
      CABG surgery from August to October 2011, in Afshar Cardiovascular Center, Yazd,
      Iran. The patients had hemoglobin concentration between 10-12 mg/dl, patients
      with preoperative atrial fibrillation and renal and respiratory dysfunction were
      excluded from this study. Participants were randomly assigned into two groups;
      the normal group (n=42) that had hemoglobin concentration ~ 12-15 g/dl and the
      anemic group (n=44) had hemoglobin concentration~7-10 g/dl. We evaluated post
      CABG variables including incidence of atrial fibrillation and early morbidity
      such as infection, vomiting, renal and respiratory dysfunctions, ICU or hospital
      stay and early mortality. Data were analyzed by ANOVA, Chi-square and Fisher's
      exact test for quantitative and qualitative variables. The mean age of the
      patients was 52.51+/-6.9 years, from all of patients 64 cases (74.4%) were male
      and 22 cases (445.6%) were female. Postoperative atrial fibrillation was observed
      in 17 cases (19.8%), 7 cases (16.7%) of whom were in normal group and 10 cases
      (22.7%) of whom were in anemia group. anemia could significantly increase
      hospital stay (P=0.0001) but no ICU stay. Preoperative anemia did not affect the
      incidence of atrial fibrillation and early complications and mortality in
      patients undergoing off-pump CABG. However, anemia could increase postoperative
      hospital stay and renal dysfunction significantly.

PMID- 23165812
TI  - Evaluation of maximum O2 consumption: using ergo-spirometry in severe heart
      failure.
AB  - Although sport-physiologists have repeatedly analyzed respiratory gases through
      exercise, it is relatively new in the cardiovascular field and is obviously more
      acceptable than standard exercise test, which gives only information about the
      existence or absence of cardiovascular diseases (CVDs). Through the new method of
      exercise test, parameters including aerobic and anaerobic are checked and
      monitored. 22 severe cases of heart failure, who were candidates of heart
      transplantation, referring to Massih Daneshvari Hospital in Tehran from Nov. 2007
      to Nov. 2008 enrolled this study. The study was designed as a cross-sectional
      performance and evaluated only patients with ejection fraction less than 30%. O2
      mean consumption was 6.27+/-4.9 ml/kg/min at rest and 9.48+/-3.38 at anaerobic
      threshold (AT) exceeding 13 ml/kg/min in maximum which was significantly more
      than the expected levels. Respiratory exchange ratio (RER) was over 1 for all
      patients. This study could not find any statistical correlations between VO2 max
      and participants' ergonomic factors such as age, height, weight, BMI, as well as
      EF. This study showed no significant correlation between VO2 max and maximum
      heart rate (HR max), although O2 maximum consumption was rationally correlated
      with expiratory ventilation. This means that the patients achieved maximum
      ventilation through exercise in this study, but failed to have their maximum
      heart rate being led probably by HF-induced brady-arrhythmia or deconditioning of
      skeletal muscles.

PMID- 23165813
TI  - Root-cause analysis of a potentially sentinel transfusion event: lessons for
      improvement of patient safety.
AB  - Errors prevention and patient safety in transfusion medicine are a serious
      concern. Errors can occur at any step in transfusion and evaluation of their root
      causes can be helpful for preventive measures. Root cause analysis as a
      structured and systematic approach can be used for identification of underlying
      causes of adverse events. To specify system vulnerabilities and illustrate the
      potential of such an approach, we describe the root cause analysis of a case of
      transfusion error in emergency ward that could have been fatal. After reporting
      of the mentioned event, through reviewing records and interviews with the
      responsible personnel, the details of the incident were elaborated. Then, an
      expert panel meeting was held to define event timeline and the care and service
      delivery problems and discuss their underlying causes, safeguards and preventive
      measures. Root cause analysis of the mentioned event demonstrated that certain
      defects of the system and the ensuing errors were main causes of the event. It
      also points out systematic corrective actions. It can be concluded that health
      care organizations should endeavor to provide opportunities to discuss errors and
      adverse events and introduce preventive measures to find areas where resources
      need to be allocated to improve patient safety.

PMID- 23165815
TI  - Musculoskeletal disorders in female dentists and pharmacists: a cross-sectional
      study.
AB  - Musculoskeletal disorders are an important occupational health problem in
      dentistry. Few studies have compared these disorders in dentists with other
      occupational groups. We assessed musculoskeletal disorders in female dentists in
      comparison with female pharmacists. A cross-sectional study by means of
      Musculoskeletal Nordic Questionnaire was performed among 191 female general
      dentists and 211 female general pharmacists who were at least one year in
      clinical practice and selected using the random sampling method. Those with a
      history of a traumatic event causing fracture in spinal column or extremities and
      connective tissue diseases excluded. The data were analyzed by univariate and
      multivariate logistic regression analyses. 91.6% of the female dentists and 87.7%
      of the female pharmacists reported having at least one musculoskeletal symptom in
      the previous 12 months. 12-month period prevalence symptoms of neck (OR=3.17),
      upper back (OR=2.19) and upper extremity (OR=1.99) had the most ORs in comparison
      of dentists to pharmacists. In summary, female dentists are at risk of developing
      musculoskeletal disorders particularly in the neck, upper back and upper
      extremities.

PMID- 23165814
TI  - Anal sphincter injuries during hemorrhoidectomy: a multi center study.
AB  - Hemorrhoidectomy is the treatment of choice for patients with third or fourth
      degree hemorrhoids. Although the majority of surgeons believe that surgical
      hemorrhoidectomy is the most effective approach with excellent results in the
      management of hemorrhoid disease, but hemorrhoidectomy is not a simple procedure.
      One of the complications of this surgery is an injury to anal sphincters that can
      lead to incontinency in some patients. In this study, we aimed to reveal the
      percentage of external and internal anal sphincter injuries in surgical
      hemorrhoidectomy. We prospectively enrolled 128 patients from April 2006 to
      February 2007. They underwent hemorrhoidectomy in three general hospitals in
      Tehran. All patients were in grade III or IV and underwent open hemorrhoidectomy
      (Milligan-Morgan). After surgery, all resected material was histopathologically
      examined by two expert pathologists and the results confirmed by other one if
      there is any discrepancy. From all specimens which sent to the pathology
      department 15.8% (21 Pts.) had muscle fibers that Smooth muscle fibers were seen
      in 80.5% (17 Pts.) of them and striated muscle fibers were found in 19.5% (4
      Pts.). Although hemorrhoidectomy is a safe and effective method for treatment of
      hemorrhoid, but the inadvertent removal of smooth and striated muscle during open
      hemorrhoidectomy had raised concerns about its effects on postoperative anorectal
      function.

PMID- 23165816
TI  - Attitudes, concerns, perceived impact and coping strategies for avian influenza
      among the first year medical students and interns in Tehran University of Medical
      Sciences.
AB  - To study and compare the attitudes, concerns, perceived impact and coping
      strategies for avian influenza (AI) among the first year medical students (FYMS)
      and interns in Tehran University of Medical Sciences. This was a cross sectional
      study carried out on FYMS (n=158) and interns (n=158) in 2008. The data
      collection tool was a questionnaire containing 37 questions in five parts. The
      three choices including "agree, disagree and unsure" were considered for all
      questions. We used Chi-square and Fisher's exact tests for analysis. Most of FYMS
      and interns (78.2%) believed their health would be depended on the care of their
      selves. Most of them (95.3%) believed that if they knew avian flu better, they
      could be more prepared for it. The majority were concerned about risk to their
      health from their work (62.7%). Most (67.7%) accepted the risk and only 5 (1.6%)
      would consider stopping work. For non-work concerns, 70.9% were concerned about
      their spouses/sexual partners and 65.8% about their children. For perceived
      impact, most (66.5%) believed that they would feel stressed at work and the
      majority (74.4%) expected an increased workload. FYMS and interns have positive
      attitudes but major concerns about contracting AI and its relation to medical
      practice.

PMID- 23165817
TI  - Unusual manifestation of cutaneous sarcoidosis: a case report of morpheaform
      sarcoidosis.
AB  - Sarcoidosis is multi organ disease with cutaneous manifestation in 20%-35%
      patients. Cutaneous sarcoidosis has variable manifestations that make it
      difficult to diagnose. So clinical, histopathologic and laboratory evaluation is
      needed for diagnosis. Most of cutaneous lesions presents as nodul, maculopapule
      and plaque. Morpheaform lesion is a rare presentation of cutaneous sarcoidosis.
      This case had multiple indurated scaly plaques resemble morphea with
      granulomatous pattern in histopathologic examination. The patient responded to
      prednisolone in addition to hydroxychloroquine.

PMID- 23165818
TI  - Intraoperative atelectasis due to endotracheal tube cuff herniation: a case
      report.
AB  - Endotracheal tube (ETT) cuff herniation is a rare, and often difficult to
      diagnose, cause of bronchial obstruction. We present a case of outside cuff
      herniation of an endotracheal tube that caused pulmonary right lung atelectasis.
      A 29-year-old man ,a case of car accident with multiple fractures, was admitted
      to the emergency ward and transferred to the operating room(OR) for open
      reduction and internal fixation (ORIF) of all fractures .The procedures were done
      under general anesthesia (G/A). The past medical history of the patient did not
      indicate any problem. Anesthesia was induced with thiopental, atracurium and then
      maintained by propofol and remifentanyl infusions and 100% O2 via orally inserted
      ETT. The patient was positioned in left lateral decubitus position for operation.
      Two hours after induction of anesthesia, the oxygen saturation level dropped to
      85 % and the breath sounds in the right side of the chest were weakened. The
      chest x-ray images showed right lung atelectasis especially in the upper lobe.
      The problem was disappeared after removal of the ETT. In this case, we observed
      that an ETT cuff herniation can be a cause of airway obstruction. If there is a
      decreased unilateral breath sounds, we recommend replacement or repositioning of
      ETT.

PMID- 23165819
TI  - "On water": efficient iron-catalyzed cycloaddition of aziridines with
      heterocumulenes.
AB  - In suspension: the reaction of aziridines with heterocumulenes in the presence of
      Fe(NO(3))(3)?9H(2)O in aqueous suspension provides access to functionalized five
      membered heterocycles in good to high yields. This protocol has a wide substrate
      scope, is simple, and uses a nontoxic and cheap catalyst.

PMID- 23165820
TI  - Hot water-promoted S(N)1 solvolysis reactions of allylic and benzylic alcohols.
AB  - During the studies of hydrolysis of epoxides in water, we found that the
      hydrolysis of (-)-alpha-pinene oxide at 20  degrees C gave enantiomerically pure
      trans-(-)-sobrerol, whereas the same reaction in water heated at reflux
      unexpectedly gave a racemic mixture of trans- and cis-sobrerol (trans/cis = 6:4).
      We have examined this remarkable difference in detail and found that hot water,
      whose behavior is quite different compared with room- or high-temperature water,
      could promote S(N)1 solvolysis reactions of allylic alcohols and thus caused the
      racemization of trans-(-)-sobrerol. The effect of reaction temperature, the
      addition of organic co-solvent, and the concentration of the solute on the rate
      of the racemization of trans-(-)-sobrerol were further examined to understand the
      role that hot water played in the reaction. It was proposed that the catalytic
      effects of hot water are owing to its mild acidic characteristic, thermal
      activation, high ionizing power, and better solubility of organic reactant.
      Further investigation showed that the racemization of other chiral
      allylic/benzylic alcohols could efficiently proceed in hot water.

PMID- 23165821
TI  - pH responsive PEGylation through metal affinity for gene delivery mediated by
      histidine-grafted polyethylenimine.
AB  - Polyethylene glycol (PEG) has been used to enhance the stability of a gene
      delivery system. The most commonly used approach is to add the PEG molecule by
      way of chemical conjugation. In this study, we prepared PEG-bearing
      nitrilotriacetic acid (ntaPEG) followed by chelation with either nickel or zinc
      ions. Polyethylenimine was grafted with histidine (hisPEI) and used as a primary
      gene carrier to form complexes with DNA. PEGylation was performed by incubating
      the complexes with chelated ntaPEG. It was noted that the coating of the chelated
      ntaPEG could provide a shielding effect against aggregation induced by bovine
      serum albumin and DNA release induced by heparin displacement, respectively. The
      coating was also found to improve cellular viability and maintain the
      transfection efficiency at a moderate level. The coated ntaPEG could dissociate
      from the complexes in an acidic condition of pH 4, suggesting that dePEGylation
      might occur in some acidic intracellular organelles, such as endosomes. This
      simple and effective PEGylation approach could be extended to other delivery
      systems to enhance the stability and to facilitate the dePEGylation process.

PMID- 23165822
TI  - Intertriginous orange-to-brownish papules and plaques: a quiz. Xanthoma
      disseminatum.

PMID- 23165823
TI  - Depressive symptoms in late life and cerebrovascular disease: the importance of
      intelligence and lesion location.
AB  - BACKGROUND: The influence of white matter lesions on depressive symptoms in
      healthy ageing populations remains unclear. In this study, we examined the
      relationship between depressive symptoms and magnetic resonance imaging (MRI)
      detected cerebrovascular disease in a normal population living independently in
      the community, and measured the influence of location of brain abnormalities,
      fluid intelligence, living alone, and sex. METHODS: Prospective cohort: 497
      community dwelling individuals all born in 1936, who took part in the Scottish
      Mental Survey of 1947, were followed up in 2000 and at biannual intervals in a
      longitudinal study of health and cognitive aging. Two hundred forty-four
      volunteered for brain MRI in 2004-2006. Suitable data were available in 219/244,
      of whom 115 were men. Brain hyperintensities in lobar white matter, basal ganglia
      , periventricular, and infratentorial regions were measured using Scheltens'
      scale. Depressed mood was assessed using the Hospital Anxiety and Depression
      Scale (HADS) on three biannual intervals. Relationships between Scheltens'
      scores, HADS-D scores, fluid intelligence, living alone, and sex were assessed
      using general linear modeling. RESULTS: The main predictor of depressive symptom
      scores was poorer fluid intelligence (partial eta(2)  =0.023-0.028, P < .05).
      Ischemic change in the brainstem (partial eta(2)  = 0.026, P <=.05) and basal
      ganglia (partial eta(2)  =0.018, P <= .05) also predicted HADS-D scores. There
      was no relationship with sex or living alone. CONCLUSIONS: Hyperintensities in
      the brainstem and basal ganglia are associated with depressive symptoms. Higher
      fluid intelligence is associated with lower depressive symptoms in this normal,
      ageing population.

PMID- 23165827
TI  - Successful treatment of bullous pemphigoid with omalizumab.

PMID- 23165828
TI  - The Person-Centered Dermatology Self-Care Index: a tool to measure education and
      support needs of patients with long-term skin conditions.
AB  - OBJECTIVE: To validate the Person-Centered Dermatology Self-Care Index (PeDeSI)
      as a tool for clinical assessment and for potential use in research evaluation.
      DESIGN: To date, no validated assessment measures exist to identify the education
      and support needs of patients living with long-term dermatological conditions and
      to enable them to self-manage as effectively as possible. The PeDeSI assessment
      tool was developed to meet this need using the self-efficacy construct and a
      model of concordance within prescribing practice. In total, 200 copies of the
      PeDeSI were distributed for validation, and 145 (72.5%) were returned completed.
      Data were analyzed using statistical software. Frequency distributions of all
      items were examined, and internal consistency was summarized using Cronbach
      alpha. Exploratory factor analysis was used to disclose any underlying structure
      among the data items. SETTING Three specialist dermatology centers in acute care
      hospitals. PARTICIPANTS: Dermatology specialist nurses treating patients with
      chronic dermatoses. INTERVENTION: A PeDeSI was completed with each patient during
      his or her usual outpatient consultation. MAIN OUTCOME MEASURE: Cronbach alpha.
      RESULTS: Cronbach alpha was 0.90, indicating good internal consistency.
      Eliminating individual items in turn made little difference in Cronbach alpha
      (range, 0.89-0.90). Item total correlations ranged from 0.44 to 0.76 (median,
      0.68). Exploratory factor analysis extracted just one factor (eigenvalue, 5.37),
      with no other factors having eigenvalues exceeding 1.00. Factor loadings on
      individual items ranged from 0.47 to 0.80. CONCLUSION The PeDeSI is a valid,
      reliable, and clinically practical tool to systematically assess the education
      and support needs of patients with long-term dermatological conditions and to
      promote treatment concordance.

PMID- 23165829
TI  - Practice gap in patient education: comment on "the person-centered dermatology
      self-care index".

PMID- 23165832
TI  - Validation of a new international quality-of-life instrument specific to
      cosmetics and physical appearance: BeautyQoL questionnaire.
AB  - OBJECTIVE: To develop a new quality-of-life (QoL) instrument with international
      validity that specifically assesses cosmetic products and physical appearance.
      DESIGN: In the first phase, semidirected interviews involved 309 subjects. In the
      second stage, an acceptability study was performed on 874 subjects. Thereafter,
      we recruited a total of 3231 subjects, each of whom completed the BeautyQoL
      questionnaire, a clinical checklist for the skin, the generic QoL 36-Item Short
      Form Health Survey, and a sociodemographic questionnaire. A retest was performed
      8 days later on a subgroup of 652 subjects. SETTING: Populations in France, the
      United Kingdom, Germany, Spain, Sweden, Italy, Russia, the United States, Brazil,
      Japan, India, China, and South Africa, representing 16 languages. PARTICIPANTS:
      The general adult healthy population, including women and men. MAIN OUTCOME
      MEASURES: Psychometric properties, construct validity, reproducibility, and
      internal and external consistency. RESULTS: General acceptability was very good
      in the 16 languages, with a very low rate of no answers. The validation phase
      reduced the questionnaire to 42 questions structured in the following 5
      dimensions that explained 76.7% of the total variance: social life, self
      confidence, mood, energy, and attractiveness. Internal consistency was high
      (Cronbach alpha coefficients, 0.93-0.98). Reproducibility at 8 days was
      satisfactory in all dimensions. Results of external validity testing revealed
      that BeautyQoL scores correlated significantly with all 36-Item Short Form Health
      Survey scores except for physical function. CONCLUSION: These results demonstrate
      the validity and reliability of the BeautyQoL questionnaire as the very first
      international instrument specific to cosmetic products and physical appearance.

PMID- 23165833
TI  - High prevalence of stump dermatoses 38 years or more after amputation.
AB  - OBJECTIVE: To highlight the prevalence and impact of skin disease at the stump
      site in patients who have undergone amputation. DESIGN: A cross-sectional health
      questionnaire of Vietnam War veterans with stump dermatoses at least 38 years
      after major limb amputation. SETTING: A research registry of veterans with combat
      related amputations who agreed to participate. PARTICIPANTS: Recruitment began
      January 1, 2006, and ended December 31, 2009, with a registry of 416 veterans.
      MAIN OUTCOME MEASURES: Results of a self-reported 35-item questionnaire.
      Participants were later contacted by telephone or asked to complete a Web survey.
      RESULTS: Of the 247 veterans, 119 (48.2%) reported at least 1 skin problem within
      the preceding year. The most common were skin breakdown (25.2%), rash (21.8%),
      and abrasion (21.0%). In addition, 25.2% experienced skin problems more than 50%
      of the time, and 37.1% had to alter or replace their prosthesis. Stump dermatoses
      limited or prevented prosthesis use in the preceding year for 55.6% and caused
      pain or discomfort at the stump site in 61.5%. CONCLUSIONS: More than 38 years
      after major limb amputation, skin complications at the stump site continue to
      cause significant morbidities and contribute to prosthesis abandonment. The high
      prevalence of stump dermatoses stresses the importance of disease prevention,
      early management, and advanced treatment of skin disease.

PMID- 23165834
TI  - Rapid healing of scar-associated chronic wounds after ablative fractional
      resurfacing.
AB  - BACKGROUND: Skin compromised by traumatic scars and contractures can manifest
      decreased resistance to shearing and other forces, while increased tension and
      skin fragility contribute to chronic erosions and ulcerations. Chronic wounds
      possess inflammatory mediator profiles and other characteristics, such as the
      presence of biofilms, that can inhibit healing. OBSERVATIONS: Three patients with
      multiple traumatic scars related to blast injuries initiated a course of ablative
      fractional laser therapy for potential mitigation of contractures, poor
      pliability, and textural irregularity. Patients also had chronic focal erosions
      or ulcerations despite professional wound care. All patients experienced
      incidental rapid healing of their chronic wounds within 2 weeks of their initial
      ablative fractional laser treatment. Healing was sustained throughout the
      treatment course and beyond and was associated with gradual enhancements in scar
      pliability, texture, durability, and range of motion. CONCLUSIONS: The unique
      pattern of injury associated with ablative fractional laser treatment may have
      various potential wound-healing advantages. These advantages include the novel
      concept of photomicrodebridement, including biofilm disruption and the
      stimulation of de novo growth factor secretion and collagen remodeling. If
      confirmed, ablative fractional resurfacing could be a potent new addition to
      traditional wound and scar treatment paradigms.

PMID- 23165836
TI  - Neutrophilic and eosinophilic dermatitis caused by contact allergic reaction to
      paraphenylenediamine in hair dye.
AB  - BACKGROUND: Paraphenylenediamine (PPD) in hair dyes can cause systemic as well as
      cutaneous allergic reactions such as neutrophilic and eosinophilic dermatitis.
      The symptoms are often severe. The acute lesion is normally histologically
      indistinguishable from any eczematous reaction with marked spongiosis.
      OBSERVATIONS: We report a case of allergic contact dermatitis caused by the use
      of hair dye containing PPD that developed in a patient who had been using the
      same hair dye for many years. Her symptoms included scalp dermatitis and
      widespread skin lesions as well as lymphadenopathy and quite possibly dyspnea
      resembling asthma. What is most remarkable about this case is the histopathologic
      finding of neutrophilic cellulitis and a marked neutrophilic infiltrate with
      variable spongiosis. This unique finding was confirmed by histologic analysis of
      a patch test lesion specimen. CONCLUSION: It is always important to consider
      contact allergic dermatitis as a cause of dermatitis because of the variable
      presentation of the disease, including unique histologic findings that do not fit
      the conventional picture, as in the present case.

PMID- 23165837
TI  - Comparative effectiveness of cryotherapy and salicylic acid for plantar warts.

PMID- 23165838
TI  - Is vulval erosive lichen planus a premalignant condition?

PMID- 23165839
TI  - Fleshy papules in areas of friction in a man with endocrine neoplasms.

PMID- 23165840
TI  - Progressive sclerotic skin lesions in a 49-year-old man.

PMID- 23165841
TI  - Scaly pruritic plaques in an HIV-positive patient.

PMID- 23165842
TI  - Diffuse skin thickening and linear papules in a 59-year-old woman.

PMID- 23165847
TI  - Computerized interactive educational tools used to improve use of sun-protective
      clothing and sunscreen: a randomized controlled study.

PMID- 23165848
TI  - Impact of bar-code labeling of clinical photographs on patient care and practice
      workflow.

PMID- 23165849
TI  - Interleukin 12/23 agents and major adverse cardiovascular events.

PMID- 23165851
TI  - Umbilical endometriosis with urachal remnant.

PMID- 23165850
TI  - Metastatic adenocarcinoma from the lung diagnosed by presenting sign of a
      hemangioma-like cutaneous lesion.

PMID- 23165852
TI  - Peripheral lymph node recurrence of tuberculosis after ustekinumab treatment.

PMID- 23165853
TI  - Paclitaxel-induced acral erythema.

PMID- 23165854
TI  - Multifocal capillary malformations due to RASA1 mutation misdiagnosed as
      cutaneous mastocytosis.

PMID- 23165855
TI  - A case of multifocal idiopathic fibrosclerosis with cutaneous involvement.

PMID- 23165857
TI  - Rorschach dermoscopy.

PMID- 23165858
TI  - Bacteriophages as templates for manufacturing supramolecular structures.
AB  - SS phages are genetically enginnered by replacing 2 N-terminal amino acids of the
      p8 coat protein of the fd phage. AGE and zeta potential measurements show that SS
      phages carry at least 1/4 less net negative surface charge than fd phages.
      Morphology and thickness of phages are studied at different counterion
      concentrations (10(-3) , 10(-2) and 10(-1)  M) by AFM, SEM and immunofluorescence
      analyses. Bundles induced by CoCl2 and CaCl2 are either metallized by chemical
      reduction or biomineralized for apatite-like material formation. EDX spectroscopy
      confirms the presence of Co, P and Ca peaks in mineralized samples. Such bottom
      up manufactured phage scaffolds might be applied in bioengineering studies.

PMID- 23165859
TI  - The risk of primary and contralateral breast cancer after ovarian cancer in
      BRCA1/BRCA2 mutation carriers: Implications for counseling.
AB  - BACKGROUND: The objective of this study was to assess the incidence of primary
      breast cancer (PBC) and contralateral breast cancer (CBC) in patients who had
      BRCA1/BRCA2-associated epithelial ovarian cancer (OC). METHODS: From the database
      of the Rotterdam Family Cancer Clinic, patients who had BRCA-associated OC
      without a history of unilateral breast cancer (BC) (at risk of PBC; n = 79) or
      with a history of unilateral BC (at risk of CBC; n = 37) were selected. The
      control groups consisted of unaffected BRCA mutation carriers (n = 351) or
      mutation carriers who had a previous unilateral BC (n = 294), respectively. The
      risks of PBC and CBC were calculated using the Kaplan-Meier survival method with
      death considered as a competing risk event. RESULTS: Women with BRCA-associated
      OC had lower 2-year, 5-year, and 10-year risks of PBC (3%, 6%, and 11%,
      respectively) compared with unaffected mutation carriers (6%, 16%, and 28%,
      respectively; P = .03), although they had a considerably higher mortality rate at
      similar time points (13%, 33%, and 61%, respectively, vs 1%, 2%, and 2%,
      respectively; P < .001). In BRCA mutation carriers with a previous unilateral BC,
      the 2-year, 5-year, and 10-year risks of CBC were nonsignificantly lower in
      patients with OC than in those without OC (0%, 7%, and 7%, respectively, vs 6%,
      16%, and 34%, respectively; P = .06), whereas the mortality rate was higher in
      patients with OC (19%, 34%, and 55%, respectively, vs 4%, 11%, and 21%,
      respectively; P < .001). CONCLUSIONS: Patients with BRCA-associated OC had a
      lower risk of developing a subsequent PBC or CBC than mutation carriers without
      OC, whereas the risk of dying from OC was greater than the risk of developing BC.
      These data may facilitate more tailored counseling for this patient subgroup,
      although confirmative studies are warranted.

PMID- 23165860
TI  - Fatal clindamycin-induced drug rash with eosinophilia and systemic symptoms
      (DRESS) syndrome.
AB  - Drug rash with eosinophilia and systemic symptoms (DRESS) syndrome is a rare,
      complex, idiosyncratic drug reaction that can be fatal. Systemic symptoms include
      lymphadenopathy, hepatic failure, and possibly renal failure. The syndrome has
      been primarily associated with anticonvulsants, whereas antimicrobials are less
      commonly associated. We describe a 63-year-old woman who initially presented with
      rash and acute kidney injury secondary to treatment with clindamycin for a
      methicillin-susceptible Staphylococcus aureus prosthetic hip infection. Her rash
      progressed to desquamation of over 90% of her body surface area. Her renal
      function progressively declined during her hospital stay, and continuous renal
      replacement therapy was started. Peripheral eosinophilia was present, and urine
      studies were consistent with intrinsic renal failure. The patient also developed
      pancreatitis, hepatic failure with elevated liver enzyme levels and coagulopathy,
      respiratory failure necessitating mechanical ventilation, and hypotension. After
      a 16-day hospitalization, life-sustaining measures were withdrawn, and the
      patient died. Use of a cutaneous adverse drug reaction scale indicated that
      clindamycin was the definite cause of this patient's DRESS syndrome. To our
      knowledge, this is the first case report of fatal clindamycin-induced DRESS
      syndrome and only the second case report of DRESS attributable to clindamycin
      therapy. Although commonly linked with anticonvulsants, clinicians should
      consider the possibility of this reaction with antimicrobials, including
      clindamycin.

PMID- 23165861
TI  - The pore size of PLGA bone implants determines the de novo formation of bone
      tissue in tibial head defects in rats.
AB  - PURPOSE: The influence of the pore size of biodegradable poly(lactic-co-glycolic
      acid) scaffolds on bone regeneration was investigated. METHODS: Cylindrical
      poly(lactic-co-glycolic acid) scaffolds were implanted into a defect in the
      tibial head of rats. Pore sizes of 100-300, 300-500, and 500-710 MUm were tested
      and compared to untreated defects as control. Two and four weeks after
      implantation, the specimens were explanted and defect regeneration and de novo
      extracellular matrix generation were investigated by MRI, quantitative solid
      state NMR, and mass spectrometry. RESULTS: The pore size of the scaffolds had a
      pronounced influence on the quantity of the extracellular matrix synthesized in
      the graft; most collagen was synthesized within the first 2 weeks of
      implantation, while the amount of hydroxyapatite increased in the second 2 weeks.
      After 4 weeks, the scaffolds contained large quantities of newly formed lamellar
      bone while the control defects were filled by inhomogenous woven bone. Best
      results were obtained for scaffolds of a pore size of 300-500 MUm. CONCLUSION:
      Our analysis showed that the structure and dynamics of the regenerated
      extracellular matrix was very similar to that of the native bone, suggesting that
      biomineralization was significantly enhanced by the choice of the most
      appropriate implant material.

PMID- 23165862
TI  - mTOR and tau phosphorylated proteins in the hippocampal tissue of rats with type
      2 diabetes and Alzheimer's disease.
AB  - This study explored the effects of mammalian target of rapamycin (mTOR) on the
      increased risk of developing Alzheimer's disease (AD) in rats with type 2
      diabetes mellitus (T2DM). Male Sprague-Dawley rats were randomly divided into
      four groups: control, T2DM, AD and T2DM+AD. Changes in the learning and memory
      abilities of the rats were observed using the Morris water maze. mTOR activity
      and tau protein hyperphosphorylation in the hippocampus were analyzed by
      immunohistochemical staining and RT-PCR. The learning and memory abilities of the
      experimental rats were weakened compared with those of the control group. The
      T2DM+AD group revealed significant changes over the T2DM and AD groups. Compared
      with the control, T2DM and AD groups, the mTOR protein and mRNA levels,
      hyperphosphorylation of tau protein and total tau protein mRNA levels were
      significantly increased in the T2DM+AD group. T2DM may excessively activate mTOR
      in the hippocampal tissue by impairing insulin signaling, thereby increasing the
      extent of tau hyperphosphorylation and promoting the occurrence of AD.

PMID- 23165863
TI  - Congenital high airway obstruction sequence (CHAOS): a new case and a review of
      phenotypic features.
AB  - Congenital high airway obstruction sequence (CHAOS) has traditionally been
      defined as airway obstruction with ultrasound evidence of distal airway
      dilatation, expanded lungs, ascites, and hydrops. It can result from aplasia or
      intrinsic obstruction to the formation of the upper airway (larynx and trachea)
      during development. CHAOS is commonly sporadic and there is no known causative
      gene. In this comprehensive review on CHAOS, we examined 117 reported cases of
      this sequence and describe a new case. Malformations in addition to high airway
      obstruction were present in 64/118 (54.2%) of patients. The most frequent
      anomalies affected the digits and musculoskeletal system, but there was no
      distinct phenotype or characteristic dysmorphic appearance associated with CHAOS.
      The ex utero intrapartum therapy (EXIT) procedure has greatly improved survival
      for these patients and 36/118 (30.5%) were alive at the time of reporting. Only 2
      patients out of 12 who underwent laryngotracheoplasty were tracheostomy-free at
      the time of their reporting. Six out of 13 were able to produce some speech. Our
      review provides valuable information on associated anomalies and survival in this
      complex sequence. The phenotypic variability seen in this review of patients
      makes it likely that the causes of CHAOS are genetically heterogeneous.

PMID- 23165864
TI  - Clinical evidence of pharmacokinetic changes in thalidomide therapy.
AB  - The teratogenic effects of thalidomide have been studied for more than 50 years.
      However, there have been few studies of the pharmacokinetic changes occurring
      during thalidomide therapy. Thalidomide was originally developed as a sedative.
      However, thalidomide induces multiple birth defects when used in pregnant women.
      Thalidomide is now used in the treatment of multiple myeloma (MM) and erythema
      nodosum leprosum (ENL) in Japan. Rational use of thalidomide is problematic due
      to a lack of basic research regarding its mechanism of action and serum
      concentration/effect relationships. There are a number of hypotheses for
      pharmacokinetic changes in thalidomide therapy. Genetic factors including single
      nucleotide polymorphisms (SNPs) that change cytochrome P450 (CYP) activity and
      epigenetic regulation that modifies CYP expression levels may contribute to the
      changes in pharmacokinetics and adverse drug reactions (ADRs) of thalidomide.
      Environmental factors include the pharmacological context of drug-drug
      interactions and the physiological context of liver diseases. Liver and kidney
      diseases do not play important roles in pharmacokinetic changes or ADRs in
      thalidomide therapy. To date, most research has focused on teratogenic activity,
      while the impact of polymorphisms in genes encoding drug metabolic enzymes and
      drug-drug interactions could mediate ADRs. Here, we discuss clinical evidence of
      pharmacokinetic changes in thalidomide therapy.

PMID- 23165865
TI  - Impact of genetic polymorphisms in CYP2C9 and CYP2C19 on the pharmacokinetics of
      clinically used drugs.
AB  - Human cytochrome P450 (CYP) is a superfamily of hemoproteins which oxidize a
      number of endogenous compounds and xenobiotics. The human CYP2C subfamily
      consists of four members: CYP2C8, CYP2C9, CYP2C18 and CYP2C19. CYP2C9 and CYP2C19
      are important drug-metabolizing enzymes and together metabolize approximately 20%
      of therapeutically used drugs. Forty-two allelic variants for CYP2C9 and 34 for
      CYP2C19 have been reported. The frequencies of these variants show marked inter
      ethnic variation. The functional consequences of genetic polymorphisms have been
      examined, and many studies have shown the clinical importance of these
      polymorphisms. Current evidence suggests that taking the genetically determined
      metabolic capacity of CYP2C9 and CYP2C19 into account has the potential to
      improve individual risk/benefit relationships. However, more prospective studies
      with clinical endpoints are needed before the paradigm of "personalized medicine"
      based on the variants can be established. This review summarizes the currently
      available important information on this topic.

PMID- 23165866
TI  - Transition metal-induced self-assembly of small molybdenum clusters.
AB  - The first-row transition metals (TMs) are applied to induce the assembly of small
      molybdenum clusters (SMCs) in the molybdenum/TM/phosphate system, and eight SMC
      based compounds are synthesized: [(V(2)O(2))(H(2)PMo(8)V(4)O(40))].2(en).12H(2)O
      (1), [CrMo(6)O(18)(OH)(6)].1.5(H(2)en).5H(2)O (2),
      [MnMo(12)O(24)(OH)(6)(HPO(4))(2)(PO(4))(6)].7(H(2)en).6H(2)O (3),
      {[Co(H(2)O)](2)[CoMo(12)O(24)(OH)(6)(H(2)PO(4))(2)(PO(4))(6)]}.4(H(2)en).4H(2)O
      (4), [Ni(5)(H(2)O)(22)(Mo(2)O(4))(8)(HPO(4))(20)(PO(4))(6)].32H(2)O (5),
      Cu(2)(en)(4)(Mo(8)O(26)) (6), [Cu(en)(2)Mo(5)O(15)(HPO(4))(2)].(H(2)en).2H(2)O
      (7) and
      {Zn(2)[Na(H(2)O)(2)][NaMo(12)O(24)(OH)(6)(H(2)PO(4))(6)(PO(4))(2)]}.5(en).11H(2)O
      (8) (en = ethylenediamine). Six kinds of SMCs as molecular building blocks have
      been observed within these eight compounds, namely, Mo(2)V, Mo(4), Mo(5),
      Mo(6)(1), Mo(6)(2) and Mo(8). In present reaction system, these TMs not only
      induce the assembly of SMCs, but also regulate the dimensionality of these
      compounds, ranging from discrete 0D to infinite 1D, 2D and 3D frameworks.
      Moreover, the electrochemical properties of compounds 1-8 are also investigated.

PMID- 23165867
TI  - Integrated information theory of consciousness: an updated account.
AB  - This article presents an updated account of integrated information theory of
      consciousness (IIT) and some of its implications. IIT stems from thought
      experiments that lead to phenomenological axioms and ontological postulates. The
      information axiom asserts that every experience is one out of many, i.e. specific
      - it is what it is by differing in its particular way from a large repertoire of
      alternatives. The integration axiom asserts that each experience is one, i.e.
      unified - it cannot be reduced to independent components. The exclusion axiom
      asserts that every experience is definite - it is limited to particular things
      and not others and flows at a particular speed and resolution. IIT formalizes
      these intuitions with three postulates. The information postulate states that
      only "differences that make a difference" from the intrinsic perspective of a
      system matter: a mechanism generates cause-effect information if its present
      state has specific past causes and specific future effects within a system. The
      integration postulate states that only information that is irreducible matters:
      mechanisms generate integrated information only to the extent that the
      information they generate cannot be partitioned into that generated within
      independent components. The exclusion postulate states that only maxima of
      integrated information matter: a mechanism specifies only one maximally
      irreducible set of past causes and future effects - a concept. A complex is a set
      of elements specifying a maximally irreducible constellation of concepts, where
      the maximum is evaluated at the optimal spatio-temporal scale. Its concepts
      specify a maximally integrated conceptual information structure or quale, which
      is identical with an experience. Finally, changes in information integration upon
      exposure to the environment reflect a system's ability to match the causal
      structure of the world. After introducing an updated definition of information
      integration and related quantities, the article presents some theoretical
      considerations about the relationship between information and causation and about
      the relational structure of concepts within a quale. It also explores the
      relationship between the temporal grain size of information integration and the
      dynamic of metastable states in the corticothalamic complex. Finally, it
      summarizes how IIT accounts for empirical findings about the neural substrate of
      consciousness, and how various aspects of phenomenology may in principle be
      addressed in terms of the geometry of information integration.

PMID- 23165868
TI  - Unresponsive wakefulness syndrome.
AB  - Recent studies providing evidence for preserved awareness in some behaviorally
      unresponsive patients stress the need to improve diagnosis in patients with
      disorders of consciousness - and stress the possible dissociation between
      responsiveness and preserved consciousness. Because active paradigms can only
      bring information in the few cases where they return positive, a major effort is
      needed to setup ancillary markers evaluating the brain's ability to generate
      consciousness without requiring the patients' collaboration - in this context,
      research on neural correlates of consciousness and coma science progress hand in
      hand.

PMID- 23165869
TI  - Clinical assessment of patients with disorders of consciousness.
AB  - The study of pathological impairments of consciousness, as they can appear in
      severely brain injured patients, can be particularly useful to better clarify
      cognitive processes and cerebral substrates which underlie consciousness. In this
      review, we will introduce the disorders of consciousness that can be presented by
      severely brain-injured patients and the behavioural scales that can be used to
      assess their level of consciousness. We will also discuss the difficulty to
      assess and detect remnant cognitive functioning in these patients.

PMID- 23165870
TI  - Cortical mechanisms of loss of consciousness: insight from TMS/EEG studies.
AB  - In a recent series of experiments we recorded the electroencephalogram (EEG)
      response to a direct cortical stimulation in humans during wakefulness, NREM
      sleep, REM sleep and anesthesia by means of a combination of transcranial
      magnetic stimulation (TMS) and high-density EEG (hd-EEG). TMS/hd-EEG measurements
      showed that, while during wakefulness and REM sleep the brain is able to sustain
      long-range specific patterns of activation, during NREM sleep and Midazolam
      induced anesthesia, when consciousness fades, this ability is lot: the
      thalamocortical system, despite being active and reactive, either breaks down in
      causally independent modules (producing a local slow wave), or it bursts into an
      explosive and non-specific response (producing a global EEG slow wave). We
      hypothesize that, like spontaneous sleep slow waves, the slow waves triggered by
      TMS during sleep and anaesthesia are due to bistability between upand down-states
      in thalamocortical circuits. In this condition, the inescapable occurrence of a
      silent, down state after an initial activation impairs the ability of
      thalamocortical circuits to sustain long-range, differentiated patterns of
      activation, a theoretical requisite for consciousness. According to animal
      experiments and computer simulations, thalamocortical bistability may result from
      increased K-currents, from alterations of the balance between excitation and
      inhibition and from partial cortical de-afferentation. We hypothesize that these
      factor may play an important role in determining loss, and recovery, of
      consciousness also in brain-injured subjects. If this is the case, some types of
      brain lesions may impair information transmission, above and beyond the
      associated anatomical disconnection, by inducing bistability in portions of the
      thalamocortical system that are otherwise healthy.

PMID- 23165871
TI  - Imaging neural signatures of consciousness: 'what', 'when', 'where' and 'how'
      does it work?
AB  - 'What' do we call consciousness? 'When' and 'Where' in the brain do conscious
      states occur, and 'How' conscious processing and conscious access to a given
      content work? In the present paper, we present a non-exhaustive overview of each
      of these 4 major issues, we provide the reader with a brief description of the
      major difficulties related to these issues, we highlight the current theoretical
      points of debate, and we advocate for the explanatory power of the "global
      workspace" model of consciousness (Baars 1989; Dehaene and Naccache 2001;
      Dehaene, Changeux et al. 2006) which can accommodate for a fairly large
      proportion of current experimental findings, and which can be used to reinterpret
      apparent contradictory findings within a single theoretical framework. Most
      notably, we emphasize the crucial importance to distinguish genuine neural
      signatures of conscious access from neural events correlated with consciousness
      but occurring either before ('upstream') or after ('downstream').

PMID- 23165872
TI  - A default mode of brain function in altered states of consciousness.
AB  - Using modern brain imaging techniques, new discoveries are being made concerning
      the spontaneous activity of the brain when it is devoid of attention-demanding
      tasks. Spatially separated patches of neuronal assemblies have been found to show
      synchronized oscillatory activity behavior and are said to be functionally
      connected. One of the most robust of these is the default mode network, which is
      associated with intrinsic processes like mind wandering and self-projection.
      Furthermore, activity in this network is anticorrelated with activity in a
      network that is linked to attention to external stimuli. The integrity of both
      networks is disturbed in altered states of consciousness, like sleep, general
      anesthesia and hypnosis. In coma and related disorders of consciousness,
      encompassing the vegetative state (unresponsive wakefulness syndrome) and
      minimally conscious state, default mode network integrity correlates with the
      level of remaining consciousness, offering the possibility of using this
      information for diagnostic and prognostic purposes. Functional brain imaging is
      currently being validated as a valuable addition to the standardized behavioral
      assessments that are already in use.

PMID- 23165873
TI  - Electrophysiological investigations of brain function in coma, vegetative and
      minimally conscious patients.
AB  - Electroencephalographic activity in the context of disorders of consciousness is
      a swiss knife like tool that can evaluate different aspects of cognitive residual
      function, detect consciousness and provide a mean to communicate with the outside
      world without using muscular channels. Standard recordings in the neurological
      department offer a first global view of the electrogenesis of a patient and can
      spot abnormal epileptiform activity and therefore guide treatment. Although
      visual patterns have a prognosis value, they are not sufficient to provide a
      diagnosis between vegetative state/unresponsive wakefulness syndrome (VS/UWS) and
      minimally conscious state (MCS) patients. Quantitative electroencephalography
      (qEEG) processes the data and retrieves features, not visible on the raw traces,
      which can then be classified. Current results using qEEG show that MCS can be
      differentiated from VS/UWS patients at the group level. Event Related Potentials
      (ERP) are triggered by varying stimuli and reflect the time course of information
      processing related to the stimuli from low-level peripheral receptive structures
      to high-order associative cortices. It is hence possible to assess auditory,
      visual, or emotive pathways. Different stimuli elicit positive or negative
      components with different time signatures. The presence of these components when
      observed in passive paradigms is usually a sign of good prognosis but it cannot
      differentiate VS/UWS and MCS patients. Recently, researchers have developed
      active paradigms showing that the amplitude of the component is modulated when
      the subject's attention is focused on a task during stimulus presentation.  Hence
      significant differences between ERPs of a patient in a passive compared to an
      active paradigm can be a proof of consciousness. An EEG-based brain-computer
      interface (BCI) can then be tested to provide the patient with a communication
      tool. BCIs have considerably improved the past two decades. However they are not
      easily adaptable to comatose patients as they can have visual or auditory
      impairments or different lesions affecting their EEG signal. Future progress will
      require large databases of resting state-EEG and ERPs experiment of patients of
      different etiologies. This will allow the identification of specific patterns
      related to the diagnostic of consciousness. Standardized procedures in the use of
      BCIs will also be needed to find the most suited technique for each individual
      patient.

PMID- 23165874
TI  - Cognitive processing during the transition to sleep.
AB  - Dramatic physiological and behavioural changes occur during the transition from
      wakefulness to sleep. The process is regarded as a grey area of consciousness
      between attentive wakefulness and slow wave sleep. Although there is evidence of
      neurophysiological integration decay as signalled by sleep EEG elements, changes
      in power spectra and coherence, thalamocortical connectivity in fMRI, and single
      neuron changes in firing patterns, little is known about the cognitive and
      behavioural dynamics of these transitions. Hereby we revise the body and brain
      physiology, behaviour and phenomenology of these changes of consciousness and
      propose an experimental framework to integrate the two aspects of consciousness
      that interact in the transition, wakefulness and awareness.

PMID- 23165875
TI  - Neural correlates of consciousness during general anesthesia using functional
      magnetic resonance imaging (fMRI).
AB  - This paper reviews the current knowledge about the mechanisms of anesthesia
      induced alteration of consciousness. It is now evident that hypnotic anesthetic
      agents have specific brain targets whose function is hierarchically altered in a
      dose-dependent manner. Higher order networks, thought to be involved in mental
      content generation, as well as sub-cortical networks involved in thalamic
      activity regulation seems to be affected first by increasing concentrations of
      hypnotic agents that enhance inhibitory neurotransmission. Lower order sensory
      networks are preserved, including thalamo-cortical connectivity into those
      networks, even at concentrations that suppress responsiveness, but cross-modal
      sensory interactions are inhibited. Thalamo-cortical connectivity into the
      consciousness networks decreases with increasing concentrations of those agents,
      and is transformed into an anti-correlated activity between the thalamus and the
      cortex for the deepest levels of sedation, when the subject is non responsive.
      Future will tell us whether these brain function alterations are also observed
      with hypnotic agents that mainly inhibit excitatory neurotransmission. The link
      between the observations made using fMRI and the identified biochemical targets
      of hypnotic anesthetic agents still remains to be identified.

PMID- 23165876
TI  - Coherent neural activity and brain synchronization during seizure-induced loss of
      consciousness.
AB  - Epileptic seizures are often characterized by profound alteration of
      consciousness (AOC). This is particularly frequent in temporal lobe seizures
      (TLS), a subgroup of seizures originating in the temporal (and usually mesial
      temporal) brain areas. The mechanisms of AOC in TLS have long been discussed and
      several theories have been proposed. Recent investigations have provided new
      hypotheses linking abnormal synchrony provoked by epileptic discharges and the
      dysfunction of brain regions involved in consciousness processing. In particular,
      the global workspace (GW) theory proposes that conscious processing results from
      coherent neuronal activity between widely distributed brain regions, with fronto
      parietal associative cortices as key elements. Recently, we have shown that AOC
      was contemporary to non-linear increases of neural synchrony within distant
      cortico-cortical and cortico-thalamic networks. We have interpreted these results
      in the light of GW theory, and suggest that excessive synchrony could prevent
      this distributed network from reaching the minimal level of differentiation and
      complexity necessary to the coding of conscious representations.

PMID- 23165877
TI  - Modes and models in disorders of consciousness science.
AB  - The clinical assessment of non-communicative brain damaged patients is extremely
      difficult and there is a need for paraclinical diagnostic markers of the level of
      consciousness. In the last few years, progress within neuroimaging has led to a
      growing body of studies investigating vegetative state and minimally conscious
      state patients, which can be classified in two main approaches. Active
      neuroimaging paradigms search for a response to command without requiring a motor
      response. Passive neuroimaging paradigms investigate spontaneous brain activity
      and brain responses to external stimuli and aim at identifying neural correlates
      of consciousness. Other passive paradigms eschew neuroimaging in favour of
      behavioural markers which reliably distinguish conscious and unconscious
      conditions in healthy controls. In order to furnish accurate diagnostic criteria,
      a mechanistic explanation of how the brain gives rise to consciousness seems
      desirable. Mechanistic and theoretical approaches could also ultimately lead to a
      unification of passive and active paradigms in a coherent diagnostic approach. In
      this paper, we survey current passive and active paradigms available for
      diagnosis of residual consciousness in vegetative state and minimally conscious
      patients. We then review the current main theories of consciousness and see how
      they can apply in this context. Finally, we discuss some avenues for future
      research in this domain.

PMID- 23165878
TI  - Sleep-dependent consolidation of motor skills in patients with narcolepsy
      cataplexy.
AB  - BACKGROUND AND OBJECTIVES: This study investigated whether the altered
      organization of post-training sleep in patients with narcolepsy-cataplexy (NC) is
      associated with a lower off-line improvement in the consolidation of motor skills
      compared with normal subjects. STUDY DESIGN: Fourteen drug-naive NC patients,
      fulfilling the international clinical and polysomnographic diagnostic criteria,
      and 14 individually-matched controls underwent training at a sequential finger
      tapping task (FTT) and were re-tested on the next morning (after a night with
      polysomnographic recording) and after another six nights (spent at home).
      SETTING: Training and retrieval sessions were performed in a controlled
      laboratory setting. RESULTS: FTT performance was worse in NC patients than
      controls at training and at both retrieval sessions and showed a fairly different
      time course (slower than in controls) of consolidation. Several sleep indices
      (lower values of stage-2 NREM sleep and SWS) were compatible with a lower
      effectiveness of sleep for consolidation of motor skills in NC patients, although
      no statistically significant relationship was found between such indices and
      improvement rate. CONCLUSION: The consolidation process of motor skills results
      less effective in NC patients since training and slower than in normal subjects
      over the week following training. The wider variations in performance scores and
      sleep parameters of post.-training night in NC patients relative to controls
      suggest that a) the lower initial consolidation may be due to a less effective
      encoding consequent to altered prior sleep, and b) the consolidation process over
      the 24 h following training is negatively influenced not only by the altered
      characteristics of post-training sleep, but also by the daytime sleepiness
      following training.

PMID- 23165879
TI  - A subcellular analysis of genetic modulation of PINK1 on mitochondrial
      alterations, autophagy and cell death.
AB  - Mutations in the PTEN-induced putative kinase1 (PINK1) represent the second most
      frequent cause of autosomal recessive Parkinson's disease. The PINK1 protein
      mainly localizes to mitochondria and interacts with a variety of proteins,
      including the pro-autophagy protein beclin1 and the ubiquitin-ligase parkin. Upon
      stress conditions, PINK1 is known to recruit parkin at the surface of
      dysfunctional mitochondria and to activate the mitophagy cascade. Aim of this
      study was to use a simple and highly reproducible catecholamine cell model and
      transmission electron microscopy to characterize whether PINK1 could affect
      mitochondrial homeostasis, the recruitment of specific proteins at mitochondria,
      mitophagy and apoptosis. Samples were analyzed both in baseline conditions and
      following treatment with methamphetamine (METH), a neurotoxic compound which
      strongly activates autophagy and produces mitochondrial damage. Our data provide
      robust sub-cellular evidence that the modulation of PINK1 levels dramatically
      affects the morphology and number of mitochondria and the amount of cell death.
      In particular, especially upon METH exposure, PINK1 is able to increase the total
      number of mitochondria, concurrently recruit beclin1, parkin and ubiquitin and
      enhance the clearance of damaged mitochondria. In the absence of functional PINK1
      and upon autophagy stress, we observe a failure of the autophagy system at large,
      with marked accumulation of dysfunctional mitochondria and dramatic increase of
      apoptotic cell death. These findings highlight the strong neuroprotective role of
      PINK1 as a key protein in the surveillance and regulation of mitochondrial
      homeostasis.

PMID- 23165880
TI  - Anthropologia transscendentalis. Kant's theory of human nature.
AB  - In recent years mankind has greatly extended its knowledge of living things, in
      general, and itself, in particular. Such a wide-ranging body of knowledge has
      consequently led to the need for a theory to encompass it, that is, a coherent
      framework in which to systematically arrange mankind's understanding of itself,
      not only with regard to its physical nature, but to its individuality and
      sociality as well. Such a theory would moreover provide the means to mediate
      between the various domains of scientific and technological enquiry, on the one
      hand, and the cultural dimensions of human society, on the other. Already in the
      18th century, Immanuel Kant strove to establish a discipline that was systematic,
      yet at the same time accessible. It was due to his efforts that philosophical
      anthropology was introduced into university curricula, to the benefit not only of
      philosophers, but of physicians and jurists as well. Kant's position is by no
      means prejudicial towards science. To the contrary, he was quite careful to
      appraise the impact of the sciences on the overall cognitive horizons of mankind
      and therefore on their potential to influence humankind's idea of itself. Clearly
      such a perspective is relevant to today's strongly felt need to reconcile modern
      neuroscience's revolutionary findings on the biological bases of the mind - of
      man's experience and behaviour - with the idea man needs of himself in order to
      orient his actions not only as individual but also as "citizen of the world" as
      well - something on which Kant worked with unremitting commitment throughout his
      entire research career. This article traces Kant's anthropological conception
      with regard to four specific issues: (1) its relation to science; (2) the
      relationship between empirical and transcendental in the speculative use and in
      practical use of reason; (3) the dialectic between what nature does and what
      human beings does, in the construction of humanity itself; (4) and finally about
      the character of the person and the character of the human species.

PMID- 23165881
TI  - Highly chemoselective carbon-carbon sigma-bond activation: nickel/Lewis acid
      catalyzed polyfluoroarylcyanation of alkynes.

PMID- 23165882
TI  - Lyotropic supramolecular helical columnar phases formed by C3-symmetric and
      unsymmetric rigid molecules.
AB  - Unlike thermotropic liquid-crystalline C(3)-symmetric molecules with flexible
      chains, the herein-designed fully rigid three-armed molecules (C(3)-symmetric and
      unsymmetric) create a fancy architecture for the formation of lyotropic liquid
      crystals in water. First, hollow columns with triple-stranded helices, analogous
      to helical rosette nanotubes, are spontaneously constructed by self-organization
      of the rigid three-armed molecules. Then, the helical nanotubes arrange into
      hexagonal liquid-crystalline phases, which show macroscopic chirality as a result
      of supramolecular chiral symmetry breaking. Interestingly, the helical nanotubes
      constructed by the fully rigid molecules are robust and stable over a wide
      concentration range in water. They are hardly affected by ionic defects at the
      molecular periphery, that is, further decoration of functional groups on the
      molecular arms can presumably be realized without changing the helical
      conformation. In addition, the formed columnar phases can be aligned
      macroscopically by simple shear and show anisotropic ionic conductivity, which
      suggests promising applications for low-dimensional ion-conductive materials.

PMID- 23165883
TI  - Sonochemical synthesis of nanomaterials.
AB  - High intensity ultrasound can be used for the production of novel materials and
      provides an unusual route to known materials without bulk high temperatures, high
      pressures, or long reaction times. Several phenomena are responsible for
      sonochemistry and specifically the production or modification of nanomaterials
      during ultrasonic irradiation. The most notable effects are consequences of
      acoustic cavitation (the formation, growth, and implosive collapse of bubbles),
      and can be categorized as primary sonochemistry (gas-phase chemistry occurring
      inside collapsing bubbles), secondary sonochemistry (solution-phase chemistry
      occurring outside the bubbles), and physical modifications (caused by high-speed
      jets or shock waves derived from bubble collapse). This tutorial review provides
      examples of how the chemical and physical effects of high intensity ultrasound
      can be exploited for the preparation or modification of a wide range of
      nanostructured materials.

PMID- 23165885
TI  - The influence of environmental factors on bone tissue engineering.
AB  - Bone repair and regeneration are dynamic processes that involve a complex
      interplay between the substrate, local and systemic cells, and the milieu.
      Although each constituent plays an integral role in faithfully recreating the
      skeleton, investigators have long focused their efforts on scaffold materials and
      design, cytokine and hormone administration, and cell-based therapies. Only
      recently have the intangible aspects of the milieu received their due attention.
      In this review, we highlight the important influence of environmental factors on
      bone tissue engineering.

PMID- 23165886
TI  - Nasal tip recontouring in primary rhinoplasty: the endonasal complete release
      approach.
AB  - OBJECTIVE: Surgery of the nasal tip is a particular challenging aspect of
      rhinoplasty. We describe a surgical concept in nasal tip surgery that is novel in
      certain aspects. It combines maneuvers that are typically reserved for the open
      approach with the minimally invasive concept of endonasal rhinoplasty. METHODS:
      Integral to the concept are the complete dissection and delivery of the lateral
      crus, repositioning of the dome, placement of alar strut grafts that extend far
      medially, and lateral advancement of the lateral crus. RESULTS: This concept of
      nasal tip recontouring through the endonasal complete release approach is
      illustrated in detail. Representative cases are displayed, and outcomes in a
      population of 100 consecutive young female primary rhinoplasty patients are
      presented. CONCLUSIONS: The concept allows for excellent cosmetic and functional
      outcomes through a minimally invasive approach with preservation of a naturally
      soft nasal tip. Patient comfort is maximized by reduced swelling, avoidance of
      nasal packing, and obviation of external incisions.

PMID- 23165884
TI  - Defining critical roles for NF-kappaB p65 and type I interferon in innate
      immunity to rhinovirus.
AB  - The importance of NF-kappaB activation and deficient anti-viral interferon
      induction in the pathogenesis of rhinovirus-induced asthma exacerbations is
      poorly understood. We provide the first in vivo evidence in man and mouse that
      rhinovirus infection enhanced bronchial epithelial cell NF-kappaB p65 nuclear
      expression, NF-kappaB p65 DNA binding in lung tissue and NF-kappaB-regulated
      airway inflammation. In vitro inhibition of NF-kappaB reduced rhinovirus-induced
      pro-inflammatory cytokines but did not affect type I/III interferon induction.
      Rhinovirus-infected p65-deficient mice exhibited reduced neutrophilic
      inflammation, yet interferon induction, antiviral responses and virus loads were
      unaffected, indicating that NF-kappaB p65 is required for pro-inflammatory
      responses, but redundant in interferon induction by rhinoviruses in vivo.
      Conversely, IFNAR1(-/-) mice exhibited enhanced neutrophilic inflammation with
      impaired antiviral immunity and increased rhinovirus replication, demonstrating
      that interferon signalling was critical to antiviral immunity. We thus provide
      new mechanistic insights into rhinovirus infection and demonstrate the
      therapeutic potential of targeting NF-kappaB p65 (to suppress inflammation but
      preserve anti-viral immunity) and type I IFN signalling (to enhance deficient
      anti-viral immunity) to treat rhinovirus-induced exacerbations of airway
      diseases.

PMID- 23165887
TI  - Medication errors and adverse drug events in kidney transplant recipients:
      incidence, risk factors, and clinical outcomes.
AB  - STUDY OBJECTIVE: To determine the incidence, risk factors, and clinical outcomes
      associated with clinically significant medication errors or adverse drug events
      in kidney transplant recipients. DESIGN: Retrospective observational study.
      SETTING: Transplant center at an academic medical center. PATIENTS: A total of
      476 adults who received kidney transplants between June 2006 and July 2009.
      MEASUREMENTS AND MAIN RESULTS: Severe or significant medication errors and
      adverse drug events (medication-related problems [MRPs]) were identified by
      medical record review. Only patient-induced medication errors (e.g., took wrong
      dose or frequency of drug, took drug not prescribed) were captured. Clinical
      outcomes included patient and graft survival, infections (including
      cytomegalovirus), readmissions, and acute rejection episodes. Thirty-seven (8%)
      of the 476 patients developed a clinically significant MRP. Univariate and
      confirmatory multivariate analyses revealed that female sex, African-American
      race, pretransplantation diabetes mellitus, delayed graft function, and
      retransplant recipients were independent risk factors for developing an MRP.
      Patients with MRPs had significantly higher rates of acute rejection (11% vs 30%,
      p=0.004), cytomegalovirus infection (15% vs 30%, p=0.033), and 30-day
      readmissions (5% vs 16%, p=0.018). Graft survival was also significantly lower in
      patients who had MRPs (p<0.001). CONCLUSION: Patient-induced medication errors
      and associated adverse drug events were common in kidney transplant recipients.
      General and transplant-specific risk factors were associated with the development
      of these MRPs, and MRPs were associated with increased risk of rejection and
      graft loss.

PMID- 23165888
TI  - Functional diffusion-weighted magnetic resonance spectroscopy of the human
      primary visual cortex at 7 T.
AB  - PURPOSE: Microstructural and metabolic changes directly related to neuronal
      activation have been investigated using functional diffusion-weighted
      spectroscopy. METHODS: The volume of interest was positioned in the primary
      visual cortex. A time series of alternating diffusion- and non-diffusion-weighted
      (1)H spectra was acquired at 7 T employing stimulated echo acquisition mode
      sequence and a long diffusion time (Delta = 245 ms). Time-resolved series of
      metabolite apparent diffusion coefficient values were derived. RESULTS:
      Significant increases in apparent diffusion coefficient of 3.3 +/- 1.4% (p =
      0.05) and 3.9 +/- 0.9% (p = 0.002) for total n-acetyl aspartate and total
      creatine, respectively, and 8.1 +/- 2.5% (p = 0.03) for total choline were
      observed in response to visual stimulation. CONCLUSION: The increase in apparent
      diffusion coefficient for these metabolites is a potential indication for
      microstructural changes in neurons during neural activation and/or for an
      increase in the energy-dependent cytoplasmic streaming associated with enhanced
      metabolism during visual stimulation.

PMID- 23165889
TI  - Prospective investigation of mental health following sexual assault.
AB  - BACKGROUND: Comorbidity in psychological disorders is common following exposure
      to a traumatic event. Relatively little is known about the manner in which
      changes in the symptoms of a given type of psychological disorder in the acute
      period following a trauma impact changes in symptoms of another disorder. This
      study investigated the relationship between changes in posttraumatic stress
      disorder (PTSD), depression, and anxiety symptoms in the first 12 weeks following
      sexual assault. METHODS: Participants were 126 women who had been sexually
      assaulted in the previous 4 weeks. RESULTS: Lower level mediation analyses
      revealed that changes in PTSD symptoms had a greater impact on changes in
      depression and anxiety than vice versa. CONCLUSIONS: The finding highlights the
      role of PTSD symptoms in influencing subsequent change in other psychological
      symptoms. These findings are discussed in the context of models detailing the
      trajectory of psychological disorders following trauma, and clinical implications
      are considered.

PMID- 23165890
TI  - Expression of pancreatic regenerating gene in lung and intestinal tissue
      correlates with the severity of disease in rats with acute necrotizing
      pancreatitis.
AB  - The aim of this study was to investigate the expression pattern of regenerating
      gene I (Reg I) in the lung and intestinal tissues of rats with acute necrotizing
      pancreatitis (ANP), as well as the correlation of Reg I expression with lung and
      intestinal injury. Sprague-Dawley rats were randomly allocated to control (n=40)
      and ANP (n=80) groups. The rats in the control group received laparotomy only. In
      the ANP group, 3% sodium taurocholate was injected into the pancreatic duct to
      develop the ANP model. Reverse transcription-polymerase chain reaction (RT-PCR)
      was performed to detect the Reg I mRNA levels in the pancreas, intestine and
      lung. The pathological changes in the pancreas, intestine and lung were observed
      and the serum amylase levels, the wet/dry weight ratio of the lung and the
      permeability of the intestinal mucosa were measured. The measured parameters were
      found to correlate with the Reg I mRNA levels. Reg I mRNA was more highly
      expressed in the pancreas, intestine and lung in the ANP rats than in the control
      group. The Reg I expression levels were positively correlated with the
      pathological scores, serum amylase levels, lung pathological scores, lung tissue
      wet/dry ratios, intestinal pathological scores and intestinal permeability. The
      levels of Reg I were increased in the lung and intestinal tissue of the ANP rats
      and the expression levels of Reg I correlated closely with the severity of the
      lung and intestinal injury.

PMID- 23165891
TI  - Pigmented necrobiosis lipoidica accompanied by insulin-dependent diabetes
      mellitus induces CD163+ proinflammatory macrophages and interleukin-17-producing
      cells.

PMID- 23165892
TI  - 1.15 Mb microdeletion in chromosome band 20p13 associated with moderate
      developmental delay-additional case and data's review.
AB  - We report on a 9-year-old girl with subtelomeric 20p microdeletion. She was
      referred for genetic counseling because of learning difficulties/school problems.
      During the evaluation short stature, hypoplastic fingernails, submucous cleft
      palate with cleft uvula, flat feet, and frequent upper respiratory infections, as
      well as the large fontanelle after birth were observed. No facial dysmorphic
      features specific for chromosomal aberrations were present. The diagnosis of
      deletion of 20p13 was established by MLPA, and delineated by arrayCGH. Our report
      describes the third individual with this approximate deletion, and presents
      detailed molecular and phenotypic characteristics providing new data supporting
      future genotype-phenotype study.

PMID- 23165893
TI  - Risk of metachronous breast cancer after BRCA mutation-associated ovarian cancer.
AB  - BACKGROUND: This study sought to estimate the risk of breast cancer (BC) after a
      diagnosis of ovarian cancer (OC) associated with mutation of the BRCA1/2 (breast
      cancer, early onset) genes (BRCA-OC). METHODS: The Memorial Sloan-Kettering
      Cancer Center and the University of Pennsylvania, clinical genetics databases
      were searched to identify women with BRCA-OC who participated in genetic testing
      and follow-up studies from 1995 to 2009. The primary objective was to determine
      the risk of developing BC after BRCA-OC. Overall survival (OS) and BC-free
      survival (BCFS) were determined by the Kaplan-Meier method; patients were
      censored at the time of last follow-up. RESULTS: A total of 164 patients had BRCA
      OC (115 with BRCA1; 49 with BRCA2). Of these 164 patients, 152 developed OC prior
      to BRCA testing (median time to testing, 2.4 years [0.01-55 years]). Median
      follow-up from OC for those not developing BC was 5.8 years (0.25-55.6 years).
      There were 46 deaths, but none were due to BC. The 5- and 10-year OS were 85%
      (95% confidence interval [CI] = 0.78, 0.90) and 68% (95% CI = 0.59, 0.76),
      respectively. There were 18 metachronous BC diagnoses. The 5- and 10-year BCFS
      were 97% (95% CI = 0.92, 0.99) and 91% (95% CI = 0.82, 0.95), respectively. A
      subset of 64 women were tested either before or within 12 months of BRCA-OC. In
      this pseudo-incident subset, 5- and 10- year OS was 71% (95% CI = 0.53, 0.83) and
      62% (95% CI = 0.44, 0.75), respectively, and 5- and 10-year BCFS were 100% and
      87% (95% CI = 0.56, 0.96), respectively. CONCLUSIONS: OS was dominated by OC
      deaths. Metachronous BC risk was lower than reported for unaffected BRCA mutation
      carriers. These results support nonsurgical management of BC risk in women with
      BRCA-OC.

PMID- 23165894
TI  - A generic one-pot route to acyclic two-coordinate silylenes from silicon(IV)
      precursors: synthesis and structural characterization of a silylsilylene.
AB  - Si in sight: a one-pot, single-step synthesis of an acyclic silylsilylene,
      Si{Si(SiMe(3))(3)}{N(SiMe(3))Dipp} (Dipp=2,6-iPr(2)C(6)H(3)), from a silicon(IV)
      starting material is reported, together with evidence for a mechanism involving
      alkali metal silylenoid intermediates.

PMID- 23165895
TI  - A cyclometallated platinum complex as a selective optical switch for quadruplex
      DNA.
AB  - Hits the spot: A cyclometalled platinum(II) complex with a substituted
      phenanthroline ligand is reported. The complex has high in vitro affinity for
      quadruplex DNA and upon binding its emission is switched on. The complex can be
      easily delivered to the cell by using a metallo-cage as a carrier (see
      illustration). By means of confocal microscopy, it is shown that the complex is
      released inside the cell, penetrates the nucleus and localises in the nucleoli.

PMID- 23165897
TI  - Antifungal susceptibility testing: a primer for clinicians.
AB  - Antifungal susceptibility testing is not as commonly performed as antibacterial
      susceptibility testing. The methodology for detecting antifungal resistance is
      newer and requires different testing supplies that may not be readily available
      in a clinical laboratory setting. Breakpoints for molds are lacking. Yeast
      breakpoints are available for most antifungals but are continually updated based
      on epidemiologic surveillance. Reliable and reproducible antifungal
      susceptibility testing methods, as well as more research on the role of
      susceptibility testing in patient care, are necessary in order to provide the
      clinician with information that can be translated into positive clinical outcomes
      at the bedside. There are nuances with current testing methods that, if
      unrecognized, could lead to misinterpretation of results and inappropriate
      antifungal selection. Clinicians who have an understanding of qualitative and
      quantitative methods, automated susceptibility testing systems, and other
      commercial tests can successfully engage this knowledge to improve antifungal use
      and patient outcomes. This primer describes the common antifungal susceptibility
      tests used in the clinical microbiology laboratory and reviews literature related
      to the impact of appropriate drug selection, timing, fungal resistance
      mechanisms, pharmacokinetics, and pharmacodynamics on clinical outcomes. Both
      conventional and modern testing methods are discussed.

PMID- 23165896
TI  - The exposure of autoantigens by microparticles underlies the formation of potent
      inflammatory components: the microparticle-associated immune complexes.
AB  - Immunoglobulins, antigens and complement can assemble to form immune complexes
      (IC). ICs can be detrimental as they propagate inflammation in autoimmune
      diseases. Like ICs, submicron extracellular vesicles termed microparticles (MP)
      are present in the synovial fluid from patients affected with autoimmune
      arthritis. We examined MPs in rheumatoid arthritis (RA) using high sensitivity
      flow cytometry and electron microscopy. We find that the MPs in RA synovial fluid
      are highly heterogeneous in size. The observed larger MPs were in fact MP
      containing ICs (mpICs) and account for the majority of the detectable ICs. These
      mpICs frequently express the integrin CD41, consistent with platelet origin.
      Despite expression of the Fc receptor FcgammaRIIa by platelet-derived MPs, we
      find that the mpICs form independently of this receptor. Rather, mpICs display
      autoantigens vimentin and fibrinogen, and recognition of these targets by anti
      citrullinated peptide antibodies contributes to the production of mpICs.
      Functionally, platelet mpICs are highly pro-inflammatory, eliciting leukotriene
      production by neutrophils. Taken together, our data suggest a unique role for
      platelet MPs as autoantigen-expressing elements capable of perpetuating formation
      of inflammatory ICs.

PMID- 23165898
TI  - Peak stress intensity factor governs crack propagation velocity in crosslinked
      ultrahigh-molecular-weight polyethylene.
AB  - Ultrahigh-molecular-weight polyethylene (UHMWPE) has been successfully used as a
      bearing material in total joint replacement components. However, these bearing
      materials can fail as a result of in vivo static and cyclic loads. Crack
      propagation behavior in this material has been considered using the Paris
      relationship which relates fatigue crack growth rate, da/dN (mm/cycle) versus the
      stress intensity factor range, DeltaK (Kmax - Kmin , MPa?m). However, recent work
      suggests that the crack propagation velocity of conventional UHMWPE is driven by
      the peak stress intensity (Kmax ), not DeltaK. The hypothesis of this study is
      that the crack propagation velocity of highly crosslinked and remelted UHMWPE is
      also driven by the peak stress intensity, Kmax , during cyclic loading. To test
      this hypothesis, two highly crosslinked (65 kGy and 100 kGy) and remelted UHMWPE
      materials were examined. Frequency, waveform, and R-ratio were varied between
      test conditions to determine the governing factor for fatigue crack propagation.
      It was found that the crack propagation velocity in crosslinked UHMWPE is also
      driven by Kmax and not DeltaK, and is dependent on loading waveform and frequency
      in a predictable quasistatic manner. This study supports that crack growth in
      crosslinked UHMWPE materials, even under cyclic loading conditions, can be
      described by a relationship between the velocity of crack growth, da/dt and the
      peak stress intensity, Kmax . The findings suggest that stable crack propagation
      can occur as a result of static loading only and this should be taken into
      consideration in design of UHMWPE total joint replacement components.

PMID- 23165899
TI  - Reproducibility and biological basis of in vivo T(2)* magnetic resonance imaging
      of liver metastasis of colorectal cancer.
AB  - In this study, the reproducibility of T2* MR imaging in colorectal liver
      metastases was assessed and T2* values were correlated with the expression of the
      hypoxia-related markers GLUT-1 and CA-IX as well as the relative vascular area,
      and the vessel density in resected tumors. The reproducibility of T2* was
      analyzed in 18 patients with in total 22 colorectal liver metastases using the
      Bland and Altman method for the 16th, 50th, and 84th percentile values.
      Immunohistochemical staining was performed on 17 resected tumors obtained from 16
      patients. The median T2* of all liver metastases was 25.0 +/- 5.6 ms vs. 23.0 +/-
      4.1 ms (median +/- st.dev.) in normal liver. The coefficient of repeatability was
      11.2 ms and the limits of agreement were -13.2 ms and 9.1 ms for median T2*
      values. On average, T2* showed fair reproducibility. No correlations between T2*
      values, hypoxia- and vascularity-related markers were observed.

PMID- 23165902
TI  - Update in wound healing in facial plastic surgery.
AB  - Many advances in wound healing have relevance to facial plastic surgery. We
      briefly highlight some of these advances, including new biological and synthetic
      products and other potential technologies to improve wound healing, as well as
      the literature describing them.

PMID- 23165903
TI  - Use of carbon dioxide laser to treat lentigo maligna and malignant melanoma in
      situ, lentigo maligna type.

PMID- 23165904
TI  - Leonardo da Vinci's aesthetic analysis of nasal tip prominence.

PMID- 23165905
TI  - Internal nasal valve functional surgery.

PMID- 23165907
TI  - The "inverted V" technique for rib cartilage L-shaped struts in rhinoplasty.

PMID- 23165908
TI  - Inability of speculation to explain dose effect differences between botulinum
      toxin products.

PMID- 23165911
TI  - Colloidal semiconductor nanocrystals: the aqueous approach.
AB  - This article summarizes the main achievements and challenges in the field of the
      aqueous synthesis of semiconductor quantum dots in colloidal solutions.
      Developments in the last two decades demonstrate the great potential of this
      approach to synthesize nanocrystalline materials with superior properties such as
      strong photoluminescence, long time stability and compatibility with biological
      media, and the variability in assembling and self-assembling into larger
      structures or on surfaces. Being relatively straightforward, the aqueous approach
      provides some advantages such as versatility, scalability, environmental
      friendliness and cost effectiveness, leading in summary to very attractive
      application perspectives.

PMID- 23165912
TI  - Confluent brownish papules and plaques on the neck, upper chest and back: a quiz.
      Confluent and reticulated papillomatosis of Gougerot and Carteaud.

PMID- 23165913
TI  - Antioxidant protective effects of lactitol against endotoxemia in patients with
      chronic viral hepatitis.
AB  - Although antiviral drugs are widely used in the clinic, progression to liver
      cirrhosis and hepatocellular carcinoma cannot yet be entirely prevented. The aim
      of this study was to determine the effects of lactitol in chronic viral hepatitis
      patients with endotoxemia. Ninety-four patients with chronic viral hepatitis were
      separated into two groups based on plasma endotoxin levels: one group with
      endotoxemia (>= 45 ng/l, n=60) and one group without endotoxemia (<45 ng/l,
      n=34). Sixty patients with gut-derived endotoxemia were randomly and evenly
      divided into a lactitol treatment group and a control group. Plasma endotoxin
      levels in patients with chronic viral hepatitis exhibited a negative correlation
      with superoxide dismutase (SOD) activity (P<0.001) and a positive correlation
      with levels of malondialdehyde (MDA) (P<0.001). The levels of SOD in the lactitol
      treated group increased (P<0.01), while the levels of MDA decreased (P<0.01).
      Plasma endotoxin levels decreased (P<0.01) and the number of lactobacilli and
      bifidobacteria in the intestinal tract increased (P<0.01 for all). These results
      suggest that lactitol administration is capable of reducing injury caused by
      oxidants through regulating intestinal flora and decreasing gut-derived
      endotoxemia in patients with chronic viral hepatitis.

PMID- 23165914
TI  - Outcome of children treated for relapsed acute lymphoblastic leukemia in Central
      America.
AB  - BACKGROUND: Outcomes for relapsed childhood acute lymphoblastic leukemia (ALL)
      have not been documented in resource-limited settings. This study examined
      survival after relapse for children with ALL in Central America. METHODS: A
      retrospective cohort study was performed and included children with first relapse
      of ALL in Guatemala, Honduras, or El Salvador between 1990 and 2011. Predictors
      of subsequent event-free survival (EFS) and overall survival (OS) were examined.
      RESULTS: There were 755 children identified with relapsed disease. The median
      time from diagnosis to relapse was 1.7 years (interquartile range, 0.8-3.1
      years). Most relapses occurred during (53.9%) or following (24.9%) maintenance
      chemotherapy, and the majority occurred in the bone marrow (63.1%). Following the
      initial relapse, subsequent 3-year EFS (+/- standard error) and OS were 22.0% +/-
      1.7%, and 28.2% +/- 1.9%, respectively. In multivariable analysis, worse
      postrelapse survival was associated with age >= 10 years, white blood cell count
      >= 50 * 10(9) /L, and positive central nervous system status at the original ALL
      diagnosis, relapse that was not isolated central nervous system or testicular,
      and relapse < 36 months following diagnosis. Site and time to relapse were used
      to identify a favorable risk group whose 3-year EFS and OS were 50.0% +/- 8.9%
      and 68.0% +/- 8.1%, respectively. CONCLUSIONS: Prognosis after relapsed ALL in
      Central America is poor, but a substantial number of those with favorable risk
      features have prolonged survival, despite lack of access to stem cell
      transplantation. Stratification by risk factors can guide therapeutic decision
      making. Cancer 2013. (c) 2012 American Cancer Society.

PMID- 23165915
TI  - An additional family with association of hereditary thrombocytosis and transverse
      limb deficiency: confirmation of a rare clinical spectrum.

PMID- 23165916
TI  - Programming in situ immunofluorescence intensities through interchangeable
      reactions of dynamic DNA complexes.
AB  - The regulation of antibody reporting intensities is critical to various in situ
      fluorescence-imaging analyses. Although such control is often necessary to
      visualize sparse molecular targets, the ability to tune marker intensities is
      also essential for highly multiplexed imaging strategies in which marker
      reporting levels must be tuned both to optimize dynamic detection ranges and to
      minimize crosstalk between different signals. Existing chemical amplification
      approaches generally lack such control. Here, we demonstrate that linear and
      branched DNA complexes can be designed to function as interchangeable building
      blocks that can be assembled into organized, fluorescence-reporting complexes. We
      show that the ability to program DNA-strand-displacement reactions between these
      complexes offers new opportunities to deterministically tune the number of dyes
      that are coupled to individual antibodies in order both to increase and
      controllably balance marker reporting levels within fixed cells.

PMID- 23165917
TI  - Key articles and guidelines in the management of acute coronary syndrome and in
      percutaneous coronary intervention: 2012 update.
AB  - More than 1 million people in the United States experience an acute coronary
      syndrome (ACS) every year, and almost 600,000 undergo percutaneous coronary
      intervention (PCI) for treatment of cardiovascular disease. There is a large
      amount of evidence-based literature to guide appropriate management of these
      patients. There have been a number of advances in the treatment of these patients
      over the last several years. Due to the large amount of rapidly available
      literature concerning the care of patients with ACS or undergoing PCI, clinicians
      can often find it difficult to keep up with the information needed for optimizing
      care of these patients. Therefore, we provide the second update to the first
      compiled bibliography of key articles and guidelines relative to patients with
      ACS published in Pharmacotherapy in 2004. The initial update was published in
      Pharmacotherapy in 2007 and also included bibliographies concerning management of
      patients undergoing PCI. A number of guidelines and practice-changing literature
      have been published since the update in 2007. Specific areas included in this
      review are updated summaries of clinical practice guidelines and clinical trials
      of anticoagulants, antiplatelets, platelet aggregation testing, pharmacogenomics
      testing in patients taking clopidogrel, clopidogrel loading dose comparisons,
      clopidogrel and proton pump inhibitor drug interactions, the impact of bleeding
      in ACS, and statins. As with previous versions of this document, we hope that
      this compilation will serve as a resource for pharmacists, physicians, nurses,
      residents, and students responsible for the care of patients with coronary heart
      disease.

PMID- 23165918
TI  - Enhanced CO2 adsorption over polymeric amines supported on heteroatom
      incorporated SBA-15 silica: impact of heteroatom type and loading on sorbent
      structure and adsorption performance.
AB  - Silica supported amine materials are promising compositions that can be used to
      effectively remove CO(2) from large stationary sources, such as flue gas
      generated from coal-fired power plants (ca. 10 % CO(2)) and potentially from
      ambient air (ca. 400 ppm CO(2)). The CO(2) adsorption characteristics of
      prototypical poly(ethyleneimine)-silica composite adsorbents can be significantly
      enhanced by altering the acid/base properties of the silica support by heteroatom
      incorporation into the silica matrix. In this study, an array of
      poly(ethyleneimine)-impregnated mesoporous silica SBA-15 materials containing
      heteroatoms (Al, Ti, Zr, and Ce) in their silica matrices are prepared and
      examined in adsorption experiments under conditions simulating flue gas (10 %
      CO(2) in Ar) and ambient air (400 ppm CO(2) in Ar) to assess the effects of
      heteroatom incorporation on the CO(2) adsorption properties. The structure of the
      composite adsorbents, including local information concerning the state of the
      incorporated heteroatoms and the overall surface properties of the silicate
      supports, are investigated in detail to draw a relationship between the adsorbent
      structure and CO(2) adsorption/desorption performance. The CO(2)
      adsorption/desorption kinetics are assessed by thermogravimetric analysis and in
      situ FT-IR measurements. These combined results, coupled with data on adsorbent
      regenerability, demonstrate a stabilizing effect of the heteroatoms on the
      poly(ethyleneimine), enhancing adsorbent capacity, adsorption kinetics,
      regenerability, and stability of the supported aminopolymers over continued
      cycling. It is suggested that the CO(2) adsorption performance of silica
      aminopolymer composites may be further enhanced in the future by more precisely
      tuning the acid/base properties of the support.

PMID- 23165920
TI  - Computational approaches to predicting essential proteins: a survey.
AB  - Essential proteins are indispensable to support cellular life. Identifying
      essential proteins can help us understand the minimal requirements for cell
      survival, which plays a significant role in the emerging field of synthetic
      biology. Moreover, essential proteins also serve as candidates of drug targets
      for developing novel therapy of diseases, such as cancer or infectious disease
      caused by emerging pathogens. However, it is expensive and time consuming to
      experimentally identify essential proteins. With accumulation of sequenced
      genomes, the gap between genome-wide essential protein data and sequence data
      become increasingly wide. Thus, computational approaches for detecting essential
      proteins are useful complements to limited experimental methods. There are many
      features related to protein essentiality. By taking advantage of these features,
      many computational approaches have been proposed to identify essential proteins.
      In this paper, we review the state-of-the-art techniques for computational
      detection of essential proteins, and discuss some challenges for future research
      in this field.

PMID- 23165919
TI  - Val66Met BDNF genotypes in melancholic depression: effects on brain structure and
      treatment outcome.
AB  - BACKGROUND: A brain-derived neurotrophic factor (BDNF) prodomain single
      nucleotide polymorphism resulting in a valine to methionine substitution
      (Val66Met) has been associated with depression-related phenotypes and brain
      alterations involving regions consistently associated with major depressive
      disorder (MDD). The aim of our study was to evaluate the association of regional
      gray matter (GM) volume within the hippocampus and other unpredicted regions at
      the whole-brain level with the BDNF Val66Met polymorphism in MDD patients with
      melancholic features and their impact on treatment outcome. METHODS: A sample of
      37 MDD inpatients was assessed with three-dimensional magnetic resonance imaging
      (1.5-T scanner). GM volume was analyzed with voxel-based morphometry (VBM) using
      Statistical Parametric Mapping (SPM5). The BDNF Val66Met variant was genotyped
      using SNPlex technology. MDD patients were classified according to genotype
      distribution under a dominant model of inheritance and thus comparing Val66
      homozygotes (n = 22) versus Met66 carriers (n = 15). RESULTS: A significant GM
      volume reduction in the left hippocampus was observed in Met66 carriers.
      Conversely, in the same group, a volume increase in the right orbitofrontal
      cortex was detected. Moreover, a significant negative correlation between left
      hippocampal volume and days to remission was found in Val66 homozygotes, whereas
      right orbitofrontal volume was inversely correlated to days to remission in Met66
      carriers. CONCLUSIONS: Our results suggest that the Val66Met BDNF variant may
      have a differential impact on the brain structure of melancholic patients with
      possible treatment outcome implications.

PMID- 23165923
TI  - The risk of hip fracture after initiating antihypertensive drugs in the elderly.
AB  - BACKGROUND: Initiating antihypertensive drugs in the elderly has been associated
      with an immediate increased risk of falls. However, it is unknown whether
      initiation of antihypertensive drugs (eg, thiazide diuretics, angiotensin II
      converting-enzyme inhibitors, angiotensin II receptor blockers, calcium channel
      blockers, or beta-adrenergic blockers) is associated with an immediate increased
      risk of hip fractures. METHODS: A population-based, self-controlled case series
      design using health care administrative databases identifying patients initiating
      an antihypertensive drug in Ontario, Canada. A cohort of newly treated
      hypertensive elderly patients was linked to the occurrence of hip fractures from
      April 1, 2000, to March 31, 2009, to create exposed cases. The risk period was
      the first 45 days following antihypertensive therapy initiation with control
      periods before and after treatment in a 450-day observation period. The outcome
      measure was the first occurrence for a proximal femoral fracture during the risk
      period. The analysis determined the relative incidence (incidence rate ratio),
      defined as the hip fracture rate in the risk period compared with control
      periods. RESULTS: Among the 301,591 newly treated hypertensive community-dwelling
      elderly patients, 1463 hip fractures were identified during the observation
      period. Hypertensive elderly persons who began receiving an antihypertensive drug
      had a 43% increased risk of having a hip fracture during the first 45 days
      following treatment initiation relative to the control periods (incidence rate
      ratio, 1.43; 95% CI, 1.19-1.72). CONCLUSIONS: Antihypertensive drugs were
      associated with an immediate increased hip fracture risk during the initiation of
      treatment in hypertensive community-dwelling elderly patients. Caution is advised
      when initiating antihypertensive drugs in the elderly.

PMID- 23165922
TI  - Mechanical and biocompatible characterizations of a readily available multilayer
      vascular graft.
AB  - There is always a considerable clinical need for vascular grafts. Considering the
      availability, physical and mechanical properties, and regenerative potential, we
      have developed and characterized readily available, strong, and compliant
      multilayer grafts that support cell culture and ingrowth. The grafts were made
      from heterogeneous materials and structures, including a thin, dense, nanofibrous
      core composed of poly-epsilon-caprolactone (PCL), and a thick, porous, hydrogel
      sleeve composed of genipin-crosslinked collagen-chitosan (GCC). Because the
      difference in physicochemical properties between PCL and GCC caused layer
      separation, the layer adhesion was identified as a determinant to graft property
      and integrity under physiological conditions. Thus, strategies to modify the
      layer interface, including increasing porosity of the PCL surface, decreasing
      hydrophobicity, and increasing interlayer crosslinking, were developed. Results
      from microscopic images showed that increasing PCL porosity was characterized by
      improved layer adhesion. The resultant graft was characterized by high compliance
      (4.5%), and desired permeability (528 mL/cm(2)/min), burst strength (695 mmHg),
      and suture strength (2.38 N) for readily grafting. Results also showed that PCL
      mainly contributed to the graft mechanical properties, whereas GCC reduced the
      water permeability. In addition to their complementary contributions to physical
      and mechanical properties, the distinct graft layers also provided layer-specific
      structures for seeding and culture of vascular endothelial and smooth muscle
      cells in vitro. Acellular graft constructs were readily used to replace abdominal
      aorta of rabbits, resulting in rapid cell ingrowth and flow reperfusion. The
      multilayer constructs capable of sustaining physiological conditions and
      promoting cellular activities could serve as a platform for future development of
      regenerative vascular grafts.

PMID- 23165924
TI  - Short-term and long-term effects of electrical stimulation on skin properties.
AB  - BACKGROUND: Electrical stimulation (ES) has been used in treating different
      medical conditions; however, not much is known about the effect of this
      application on skin properties. The purpose of this study was to investigate the
      short-term and long-term effects of ES on biophysical properties of the skin.
      METHODS: A pretest-posttest control design was used in the study. Thirteen men (N
      = 13, age (M +/- SD), 19 +/- 5.6 years) were free of skin abnormality on the
      volar aspect of both forearms. Four areas were allocated and marked with a layout
      template of two circles 2 cm in diameter and 2 cm apart. Areas 1 and 2 were
      allocated on the experimental forearm and area 3 and 4 on the control forearm. ES
      was applied for 15 minutes with two rubber electrodes 8 cm apart surrounding
      areas 1 and 2 on the experimental forearm three times a week for 2 weeks. Skin
      properties including transepidermal water loss (TEWL), melanin content, erythema,
      elasticity and pH were measured pre-ES, during ES and post-ES, and after 2 weeks
      of applying ES to find out the short-term and long-term effects on skin. RESULTS:
      The TEWL was increased during ES at 7, 15 and 15-minutes post-ES compared with
      the baseline (p < 0.01) and to the control forearm (p = 0.04) measurements, and
      no increase have been noticed of TEWL on the control forearm (p = 0.11). Also, we
      found no difference in the other skin properties (p > 0.05) on both forearms, and
      there were no long-term effects (p > 0.05) in any tested variable. CONCLUSION:
      Electrical stimulation caused temporary increase in TEWL with no effects on other
      skin properties.

PMID- 23165925
TI  - Competitive formation of both long-range 5'-5' and short-range antiparallel 3'-3'
      DNA interstrand cross-links by a trinuclear platinum complex on binding to a 10
      mer duplex.
AB  - 2D [(1)H, (15)N] HSQC NMR spectroscopy has been used to monitor the reaction of
      fully (15)N-labelled [{trans-PtCl(NH(3))(2)}(2)(MU-trans
      Pt(NH(3))(2){NH(2)(CH(2))(6)NH(2)}(2))](4+) (Triplatin, BBR3464 or 1,0,1/t,t,t
      ((15)N-1)) with the self-complementary 10-mer DNA duplex 5'-{d(ACGTATACGT)(2)}
      (duplex I) at pH 5.4 and 298 K. Initial electrostatic interactions were observed
      in the minor groove of the duplex, followed directly by aquation to form the
      monoaqua monochloro species. There was evidence for two discrete monofunctional
      adducts, through covalent binding at the guanine N7 sites, and one had distinctly
      different (1)H/(15)N chemical shifts to those observed previously in analogous
      reactions. Bifunctional adduct formation followed by binding at a second guanine
      N7 site with evidence for both the 3'-3' 1,2-GG and 5'-5' 1,6-GG interstrand
      cross-links in a ratio of 2 : 1. The results show that cross-link preference is
      kinetically controlled and will depend critically on the reaction conditions,
      explaining why in a previous reaction of 1 with duplex I the major adduct
      isolated by HPLC had two simultaneous 3'-3' 1,2-interstrand cross-links.

PMID- 23165926
TI  - Structural characterization of bacterial lipopolysaccharides with mass
      spectrometry and on- and off-line separation techniques.
AB  - The focus of this review is the application of mass spectrometry to the
      structural characterization of bacterial lipopolysaccharides (LPSs), also
      referred to as "endotoxins," because they elicit the strong immune response in
      infected organisms. Recently, a wide variety of MS-based applications have been
      implemented to the structure elucidation of LPS. Methodological improvements, as
      well as on- and off-line separation procedures, proved the versatility of mass
      spectrometry to study complex LPS mixtures. Special attention is given in the
      review to the tandem mass spectrometric methods and protocols for the analyses of
      lipid A, the endotoxic principle of LPS. We compare and evaluate the different
      ionization techniques (MALDI, ESI) in view of their use in intact R- and S-type
      LPS and lipid A studies. Methods for sample preparation of LPS prior to mass
      spectrometric analysis are also described. The direct identification of intrinsic
      heterogeneities of most intact LPS and lipid A preparations is a particular
      challenge, for which separation techniques (e.g., TLC, slab-PAGE, CE, GC, HPLC)
      combined with mass spectrometry are often necessary. A brief summary of these
      combined methodologies to profile LPS molecular species is provided.

PMID- 23165927
TI  - A family-based paradigm to identify candidate chromosomal regions for isolated
      congenital diaphragmatic hernia.
AB  - Congenital diaphragmatic hernia (CDH) is a developmental defect of the diaphragm
      that causes high newborn mortality. Isolated or non-syndromic CDH is considered a
      multifactorial disease, with strong evidence implicating genetic factors. As low
      heritability has been reported in isolated CDH, family-based genetic methods have
      yet to identify the genetic factors associated with the defect. Using the Utah
      Population Database, we identified distantly related patients from several
      extended families with a high incidence of isolated CDH. Using high-density
      genotyping, seven patients were analyzed by homozygosity exclusion rare allele
      mapping (HERAM) and phased haplotype sharing (HapShare), two methods we developed
      to map shared chromosome regions. Our patient cohort shared three regions not
      previously associated with CDH, that is, 2q11.2-q12.1, 4p13 and 7q11.2, and two
      regions previously involved in CDH, that is, 8p23.1 and 15q26.2. The latter
      regions contain GATA4 and NR2F2, two genes implicated in diaphragm formation in
      mice. Interestingly, three patients shared the 8p23.1 locus and one of them also
      harbored the 15q26.2 segment. No coding variants were identified in GATA4 or
      NR2F2, but a rare shared variant was found in intron 1 of GATA4. This work shows
      the role of heritability in isolated CDH. Our family-based strategy uncovers new
      chromosomal regions possibly associated with disease, and suggests that non
      coding variants of GATA4 and NR2F2 may contribute to the development of isolated
      CDH. This approach could speed up the discovery of the genes and regulatory
      elements causing multifactorial diseases, such as isolated CDH.

PMID- 23165929
TI  - Pigmented epithelioid melanocytoma: immunohistochemical profiles of tumour
      infiltrating histiocytes.

PMID- 23165931
TI  - Dynamics of a microliquid prism actuated by electrowetting.
AB  - A microliquid prism is a microchannel filled with two immiscible liquids, whose
      interface acts as a refractive surface. To steer a light beam that constructs
      optical images, the interface profile or the contact angle is modulated through
      electrowetting on a dielectric. Accurate, yet agile actuation of the liquid prism
      critically depends on the understanding of dynamics of the fluid interface. Here
      we fabricate liquid prisms, visualize the shape evolution of the interface, and
      theoretically model its dynamics. By comparing the magnitude of capillary forces
      to those of viscous, inertial and hydrostatic forces, we find that the meniscus
      motion within submillimetric channels is dominated by the capillary effect. The
      theoretical predictions for microscale meniscus dynamics are shown to agree well
      with the experimental measurements. We then discuss the formation of waves in
      millimetric liquid prisms, which may significantly limit fast and reliable
      operation of the optofluidic device.

PMID- 23165930
TI  - Identification, characterization, and isolation of a common progenitor for
      osteoclasts, macrophages, and dendritic cells from murine bone marrow and
      periphery.
AB  - Osteoclasts are specialized bone-resorbing cells that derive from monocyte
      precursors. We have identified three populations of cells with high
      osteoclastogenic potential in murine bone marrow, which expressed the phenotype
      B220(-) CD3(-) CD11b(-/low) CD115(+) and either CD117(hi), CD117(intermediate),
      or CD117(low). We have evaluated these populations for their ability to also
      generate macrophages and dendritic cells. At a single-cell level, the population
      expressing higher CD117 levels was able to generate bone-resorbing osteoclasts,
      phagocytic macrophages, and antigen-presenting dendritic cells in vitro with
      efficiencies of more than 90%, indicating that there exists a common
      developmental pathway for these cell types. Cells with osteoclastogenic potential
      also exist in blood and peripheral hematopoietic organs. Their functional meaning
      and/or their relationship with bone marrow progenitors is not well established.
      Hence, we characterized murine peripheral cell populations for their ability to
      form osteoclasts, macrophages, and dendritic cells in vitro. The spleen and
      peripheral blood monocyte progenitors share phenotypic markers with bone marrow
      progenitors but differ in their expression of CD11b, which was low in bone marrow
      but high in periphery. We propose that circulating monocyte progenitors are
      derived from a common bone marrow osteoclasts/macrophage/dendritic cell
      progenitor (OcMDC), which we have now characterized at a clonal level. However,
      the lineage relationship between the bone marrow and peripheral monocyte
      progenitors has yet to be defined.

PMID- 23165932
TI  - Direct identification of rat iNKT cells reveals remarkable similarities to human
      iNKT cells and a profound deficiency in LEW rats.
AB  - iNKT cells are a particular lymphocyte population with potent immunomodulatory
      capa-city; by promoting or suppressing immune responses against infections,
      tumors, and autoimmunity, iNKT cells are a promising target for immunotherapy.
      The hallmark of iNKT cells is the expression of a semiinvariant TCR (with an
      invariant alpha-chain comprising AV14 and AJ18 gene segments), which recognizes
      glycolipids presented by CD1d. Here, we identified iNKT cells for the first time
      in the rat using rat CD1d-dimers and PLZF staining. Importantly, in terms of
      frequencies (1.05% +/- 0.52 SD of all intrahepatic alphabeta T cells), coreceptor
      expression and in vitro expansion features, iNKT cells from F344 inbred rats more
      closely resemble human iNKT cells than their mouse counterparts. In contrast, in
      LEW inbred rats, which are often used as models for organ-specific autoimmune
      diseases, iNKT cell numbers are near or below the detection limit. Interestingly,
      the usage of members of the rat AV14 gene family differed between F344 and LEW
      inbred rats. In conclusion, the similarities between F344 rat and human iNKT
      cells and the nearly absent iNKT cells in LEW rats make the rat a promising
      animal model for the study of iNKT cell-based therapies and of iNKT-cell biology.

PMID- 23165933
TI  - Functional independence of Taiwanese children with VACTERL association.
AB  - VACTERL association is a non-random association of birth defects, which may
      include anomalies of the vertebral column, limbs, kidneys, and heart; anal
      atresia; tracheoesophageal fistula; and esophageal atresia. The presence of two
      or more of the defects establishes the diagnosis. The aim of our study is to
      describe the functional independence of children with VACTERL association and
      compare the results to unaffected children. These results will enable clinicians
      to provide more realistic prognostic information to parents and families. We used
      the WeeFIM questionnaire to assess the functional skills of 23 patients who had
      been diagnosed with VACTERL association at Mackay Memorial Hospital, Taipei,
      Taiwan, from June 1994 to June 2009. The total WeeFIM scores and sub-scores for
      three domains (self-care, mobility, and cognition) correlated significantly with
      age (P < 0.01). The scores were generally within the same range as those of
      unaffected Chinese children, although our subjects had slightly inferior scores
      on six items, including bowel, chair transfer, stairs, expression, social
      interaction, and problem solving. In conclusion, the daily functional skills of
      Taiwanese children with VACTERL association were similar to those of unaffected
      children.

PMID- 23165934
TI  - Comparison of R2* correction methods for accurate fat quantification in fatty
      liver.
AB  - PURPOSE: To compare the performance of fat fraction quantification using single
      R(2)* and dual-R(2)* correction methods in patients with fatty liver, using MR
      spectroscopy (MRS) as the reference standard. MATERIALS AND METHODS: From a group
      of 97 patients, 32 patients with hepatic fat fraction greater than 5%, as
      measured by MRS, were identified. In these patients, chemical shift encoded fat
      water imaging was performed, covering the entire liver in a single breathhold.
      Fat fraction was measured from the imaging data by postprocessing using 6
      different models: single- and dual-R(2)* correction, each performed with complex
      fitting, magnitude fitting, and mixed magnitude/complex fitting to compare the
      effects of phase error correction. Fat fraction measurements were compared with
      co-registered spectroscopy measurements using linear regression. RESULTS: Linear
      regression demonstrated higher agreement with MRS using single-R(2)* correction
      compared with dual-R(2)* correction. Among single-R(2)* models, all 3 fittings
      methods performed similarly well (slope = 1.0 +/- 0.06, r(2) = 0.89-0.91).
      CONCLUSION: Single-R(2)* modeling is more accurate than dual-R(2)* modeling for
      hepatic fat quantification in patients, even in those with high hepatic fat
      concentrations.

PMID- 23165935
TI  - Exchange-linked dissolution agents in dissolution-DNP (13)C metabolic imaging.
AB  - PURPOSE: The use of unlabeled exchange-linked dissolution agents in
      hyperpolarized metabolic imaging was studied to examine pool size limits and
      saturation relative to the availability of NADH. METHODS: Three-dimensional
      dynamic metabolic images were obtained, and compared following injection of a
      bolus of hyperpolarized [1-(13)C]pyruvate, prepared with and without unlabeled
      sodium lactate in the dissolution buffer. Comparisons were made on the basis of
      apparent rate constants and [1-(13)C]lactate signal-to-noise ratio. Range finding
      data were obtained for different bolus compositions. Isotope exchange was also
      probed in the reverse direction, following injection of a bolus of hyperpolarized
      [1-(13)C]lactate, with and without unlabeled sodium pyruvate in the dissolution
      buffer. RESULTS: Liver, kidney, and vascular regions of interest all showed an
      increase in [1-(13)C]lactate signal with addition of unlabeled sodium lactate in
      the dissolution buffer. Injection of hyperpolarized [1-(13)C]lactate with
      unlabeled sodium pyruvate in the dissolution buffer, provided exchange rate
      constants Klp for kidney and vascular regions of interest. CONCLUSIONS: These
      results are consistent with a high level of (13)C-exchange, and with labeling
      rates that are limited by steady-state pool sizes in vivo.

PMID- 23165936
TI  - Roughness statistical influence on cell adhesion using profilometry and
      multiscale analysis.
AB  - In this study, two series of 11 samples of TiAl6V4 titanium alloy and 316L
      stainless steel have been polished in an isotropic manner at different levels in
      order to quantify the influence of biomaterial roughness on cell behavior.
      Topography was measured by a tactile profilometer and a multiscale analysis has
      been carried out. Human osteoblasts have been cultured on those samples. It
      appears that roughness has no reproducible effect on the cell behavior except an
      influence on cell orientation on the wider grooves. As a conclusion, biomaterial
      surface damage, in the roughness range between Ra = 0.01 and 0.1 MUm, has no
      influence on cell-adhesion mechanisms when roughness is isotropic and groove
      width is inferior to a critical value.

PMID- 23165928
TI  - Ribosomally synthesized and post-translationally modified peptide natural
      products: overview and recommendations for a universal nomenclature.
AB  - This review presents recommended nomenclature for the biosynthesis of ribosomally
      synthesized and post-translationally modified peptides (RiPPs), a rapidly growing
      class of natural products. The current knowledge regarding the biosynthesis of
      the >20 distinct compound classes is also reviewed, and commonalities are
      discussed.

PMID- 23165937
TI  - Dicer-processed small RNAs: rules and exceptions.
AB  - Canonical microRNAs are excised from their hairpin-shaped precursors by Dicer. In
      order to find possible exceptions to this rule and to identify additional
      substrates for Dicer processing we re-evaluate the small RNA sequencing data of
      the Dicer knockdown experiment in MCF-7 cells orignally published by Friedlander
      et al. [Friedlander et al., 2012, Nucleic Acids Res 40:37-52]. While the well
      known non-Dicer mir-451 is not sufficiently expressed in these experiments, there
      are several additional Dicer-independent microRNAs, among them the important
      tumor supressor mir-663a. We recover previously described examples of non-miRNA
      Dicer substrates such as tRNA-Gln and several snoRNAs. Interestingly, sdRNAs
      derived from box C/D snoRNAs are Dicer-independent, while those derived from box
      H/ACA snoRNAs are often Dicer dependent. Several pol-III transcripts, in
      particular the vault RNAs and the great ape specific snaRs are processed by
      Dicer, while the small RNAs originating from Y RNAs seem to be Dicer independent.

PMID- 23165938
TI  - Biosynthesis of archetypal plant self-defensive oxylipins by an endophytic fungus
      residing in mangrove embryos.
AB  - A tree's travel companion: a fungal endophyte (Fusarium incarnatum) isolated from
      a viviparous propagule (embryo) of a mangrove tree produces typical plant defense
      oxylipins. Stable-isotope labeling experiments revealed that the endophyte
      biosynthesizes coriolic acid, didehydrocoriolic acid, and an epoxy fatty acid
      derived from linoleic acid by a process involving Delta(15)-desaturation and 13
      lipoxygenation.

PMID- 23165939
TI  - Glycyrrhiza uralensis flavonoids present in anti-asthma formula, ASHMITM, inhibit
      memory Th2 responses in vitro and in vivo.
AB  - Allergic asthma is associated with Th2-mediated inflammation. Several flavonoids
      were isolated from Glycyrrhiza uralensis, one of the herbs in the anti-asthma
      herbal medicine intervention. The aim of this investigation was to determine
      whether Glycyrrhiza uralensis flavonoids have inhibitory effects on memory Th2
      responses in vitro and antigen-induced Th2 inflammation in vivo. The effects of
      three Glycyrrhiza uralensis flavonoids on effector memory Th2 cells, D10.G4.1
      (D10 cells), were determined by measuring Th2 cytokine production.
      Isoliquiritigenin, 7, 4'-dihydroxyflavone (7, 4'-DHF) and liquiritigenin
      significantly suppressed IL-4 and IL-5 production in a dose-dependent manner, 7,
      4'-DHF being most potent. It was also evaluated for effects on D10 cell
      proliferation, GATA-3 expression and IL-4 mRNA expression, which were suppressed,
      with no loss of cell viability. Chronic treatment with 7, 4'-DHF in a murine
      model of allergic asthma not only significantly reduced eosinophilic pulmonary
      inflammation, serum IgE levels, IL-4 and IL-13 levels, but also increased IFN
      gamma production in lung cell cultures in response to antigen stimulation.

PMID- 23165940
TI  - Core2 O-glycan-expressing prostate cancer cells are resistant to NK cell
      immunity.
AB  - Core2 beta-1,6-N-acetylglucosaminyltransferase (C2GnT) forms an N
      acetylglucosamine branch in the O-glycans (core2 O-glycans) of cell surface
      glycoproteins. We previously revealed that the expression of C2GnT is positively
      correlated with poor prognosis in prostate cancer patients. However, the detailed
      mechanisms underlying their poor prognosis remain unclear. In the current study,
      we report that the core2 O-glycans carried by the surface MUC1 glycoproteins of
      prostate cancer cells play an important role in the evasion of NK cell immunity.
      In C2GnT-expressing prostate cancer cells, the MUC1 core2 O-glycans are modified
      with poly-N-acetyllactosamine. MUC1 glycoproteins carrying poly-N
      acetyllactosamine attenuated the interaction of the cancer cells with NK cells,
      resulting in decreased secretion of granzyme B by the NK cells. Poly-N
      acetyllactosamine also interfered with the ability of tumor necrosis factor
      related apoptosis-inducing ligand (TRAIL) to access the cancer cell surface.
      These effects of poly-N-acetyllactosamine on NK cells render C2GnT-expressing
      prostate cancer cells resistant to NK cell cytotoxicity. By contrast, C2GnT
      deficient prostate cancer cells carrying a lower amount of poly-N
      acetyllactosamine than the C2GnT-expressing prostate cancer cells were
      significantly more susceptible to NK cell cytotoxicity. Our results strongly
      suggest that C2GnT-expressing prostate cancer cells evade NK cell immunity and
      survive longer in the host blood circulation, thereby resulting in the promotion
      of prostate cancer metastasis.

PMID- 23165941
TI  - Dysfunctional cortico-basal ganglia-thalamic circuit and altered hippocampal
      amygdala activity on cognitive set-shifting in non-neuropsychiatric systemic
      lupus erythematosus.
AB  - OBJECTIVE: To explore sequential brain activities throughout cognitive set
      shifting, which is critical to understanding the basic pathophysiology of
      cognitive dysfunction, in patients with new-onset systemic lupus erythematosus
      (SLE) without neuropsychiatric symptoms. METHODS: Fourteen patients with new
      onset SLE but without neuropsychiatric symptoms and 14 healthy controls matched
      for age, sex, education level, and intelligence quotient with the patients
      performed a cognitive set-shifting task derived from the Wisconsin Card Sorting
      Test while they were undergoing event-related functional magnetic resonance
      imaging of the brain. Blood oxygen level-dependent signals were compared between
      different stages of cognitive set-shifting in the lupus patients and in the
      healthy subjects. RESULTS: Lupus patients and healthy subjects demonstrated
      comparable cognitive function performance, but the cortico-basal ganglia-thalamic
      cortical circuit and amygdala-hippocampus coupling, which were involved in
      response inhibition and active forgetting-learning dynamics, respectively, were
      demonstrated to be compromised in patients with SLE. Moreover, an increase in
      contralateral cerebellar-frontal activity was found to compensate for the
      compromised cortico-basal ganglia-thalamic-cortical circuit in lupus patients in
      order to maintain their cognitive test performance as comparable to that of the
      healthy subjects. CONCLUSION: Our study revealed significant differences in the
      sequential brain signals during cognitive set-shifting between patients with SLE
      without neuropsychiatric symptoms and healthy subjects. The results prompt
      further in-depth investigation for the functional neural basis of cognitive
      dysfunction involving the aforementioned neural circuits and compensatory
      pathways in patients with SLE.

PMID- 23165942
TI  - Infrasound sensitizes human glioblastoma cells to cisplatin-induced apoptosis.
AB  - The development of nontoxic agents that can selectively enhance the cytotoxicity
      of chemotherapy is an important aim in oncology. This study evaluates the ability
      of infrasound exposure to sensitize glioblastoma cells to cisplatin-induced
      apoptosis. The infrasound was delivered using a device designed to replicate the
      unique infrasound emissions measured during external Qigong treatments. Human
      glioblastoma cell lines harboring wild-type p53 (U87) or mutant p53 (U251, SF210,
      and SF188) were treated in culture with cisplatin, infrasound emissions, or the
      combination of the 2 agents. Induction of apoptosis was quantified after 24 hours
      by flow cytometry following annexin V/propidium iodide staining. Infrasound
      emissions alone, delivered at moderate levels (~10 mPa) with dynamic frequency
      content (7-13 Hz), did not induce apoptosis, yet combining infrasound with
      cisplatin augmented the induction of apoptosis by cisplatin in all the 4 cell
      lines (P < .05). Increased cellular uptake of the fluorophore calcein associated
      with infrasound exposure was quantified by fluorescence microscopy as well as
      flow cytometry, demonstrating increased cell membrane permeability. The 4 cell
      lines differed in the degree to which infrasound exposure increased calcein
      uptake, and these differences were predictive of the extent to which infrasound
      enhanced cisplatin-induced apoptosis. When exposed to specific frequencies,
      membrane permeabilization also appeared to be differentially responsive for each
      cell line, suggesting the potential for selective targeting of tissue types using
      isolated infrasonic frequencies. Additionally, the pressure amplitudes used in
      this study were several orders of magnitude less than those used in similar
      studies involving ultrasound and shock waves. The results of this study provide
      support for using infrasound to enhance the chemotherapeutic effects of cisplatin
      in a clinical setting.

PMID- 23165943
TI  - Evolution of research on the effect of unemployment on acute myocardial
      infarction risk.

PMID- 23165944
TI  - Morphogenesis of the manubrium of sternum in human embryos: a new concept.
AB  - To revisit many theories on fetal development of the manubrium of the sternum, we
      examined 25 mid-term fetuses at 6-9 weeks of gestation. The initial developmental
      stage of the manubrium was characterized by a distinct interclavicular mesenchyme
      that was continuous with the developing clavicles. Because parts of the clavicle
      in which endochondral ossification occurs originate from the neural crest, the
      interclavicular mesenchyme seems to be of the same origin. The sternal bands,
      possibly of the lateral plate origin, were restricted at the anterior ends of the
      ribs in the paired thoracic walls. The interclavicular mesenchyme extended
      caudally and laterally to reach the anterior ends of the first ribs, and thus the
      interclavicular mesenchyme expanded into the intercostoclavicular mesenchyme.
      Then, the primitive manubrium was delimited by the sternoclavicular joint and its
      related ligaments, all of which developed from the interclavicular and
      intercostoclavicular mesenchymes. Although the first ribs were attached to the
      intercostoclavicular mesenchyme, the former was vimentin-negative in contrast to
      the latter, positive mesenchyme. Soon afterwards, the small upper end of the
      sternal bands was integrated into the intercostoclavicular mesenchyme to form the
      primitive manubrium. The infrahyoid muscles and their supplying nerves maintained
      a close topographical relation to the interclavicular or intercostoclavicular
      mesenchyme, whereas the pectoralis major muscle kept attachments to the sternal
      bands. Consequently, the manubrium of sternum appeared to develop in a complex
      way at a junction area between derivatives of the neural crest, lateral plate,
      and somite.

PMID- 23165945
TI  - Unsymmetrical octanuclear Schiff base clusters: synthesis, characterization and
      catalysis.
AB  - The synthesis and characterization of nonsymmetrical octanuclear Schiff base
      clusters derived from nonsymmetrical diamine precursors is reported. These
      cluster complexes, typically assemblies comprising of four bimetallic salphen
      units, are isolated as a mixture of geometrical isomers as a result of different
      relative positions of the peripheral groups present in the diamine connectors
      within each cluster compound. A variety of peripheral groups can be installed
      including aryl bromides, protected carboxylic acids and pyridyl functionalities.
      The analysis of these octanuclear systems has been challenging, though mass
      spectrometric analysis provides a useful and diagnostic tool for the
      straightforward determination of the mono-disperse nature of these products. The
      presence of various electron-withdrawing and -donating groups on the peripheral
      aryl fragment allows for electronic modulation as supported by the application of
      these cluster derivatives in the homogeneous catalytic conversion of epoxides
      into their respective cyclic carbonates.

PMID- 23165947
TI  - So long, and thanks for all the papers.

PMID- 23165946
TI  - Congenital diaphragmatic hernia interval on chromosome 8p23.1 characterized by
      genetics and protein interaction networks.
AB  - Chromosome 8p23.1 is a common hotspot associated with major congenital
      malformations, including congenital diaphragmatic hernia (CDH) and cardiac
      defects. We present findings from high-resolution arrays in patients who carry a
      loss (n = 18) or a gain (n = 1) of sub-band 8p23.1. We confirm a region involved
      in both diaphragmatic and heart malformations. Results from a novel CNVConnect
      algorithm, prioritizing protein-protein interactions between products of genes in
      the 8p23.1 hotspot and products of previously known CDH causing genes, implicated
      GATA4, NEIL2, and SOX7 in diaphragmatic defects. Sequence analysis of these genes
      in 226 chromosomally normal CDH patients, as well as in a small number of
      deletion 8p23.1 patients, showed rare unreported variants in the coding region;
      these may be contributing to the diaphragmatic phenotype. We also demonstrated
      that two of these three genes were expressed in the E11.5-12.5 primordial mouse
      diaphragm, the developmental stage at which CDH is thought to occur. This
      combination of bioinformatics and expression studies can be applied to other
      chromosomal hotspots, as well as private microdeletions or microduplications, to
      identify causative genes and their interaction networks.

PMID- 23165948
TI  - Bragg extraction of light in 2D photonic Thue-Morse quasicrystals patterned in
      active CdSe/CdS nanorod-polymer nanocomposites.
AB  - In this paper two-dimensional (2D) photonic Thue-Morse quasicrystals (ThMo-PQCs)
      in active CdSe/CdS nanorod (NR) doped polymer nanocomposites are proposed and
      experimentally demonstrated. Active PQCs and undoped lattices have been prepared
      in a one-step fabrication process by an electron beam lithography technique (EBL)
      and the effects on light extraction and emission directionality are studied
      experimentally. Vertical extraction of light was found to be strongly dependent
      on both the geometric parameters of the ThMo-PQCs and the presence of NR dopants.
      By changing the geometrical parameters of the photonic structures, the resonance
      peak could be tuned from a narrow bluish green emission at 543 nm up to a red-NIR
      emission at 711 nm with a full width at half-maximum of 22 nm which is in good
      agreement with Bragg's diffraction theory and free photon band structure. Angular
      resolved measurements revealed a directional profile in the far-field
      distribution with guided mode extraction in both doped and undoped PQCs and an
      enhancement as high as 6.5-fold in light extraction was achieved in the doped
      photonic structures. These experimental results indicate the critical role of the
      CdSe/CdS NRs in improving the light extraction efficiency of 2D ThMo-PQCs for
      solid-state lighting and lasing.

PMID- 23165949
TI  - Proteomics analysis of tumor microenvironment: Implications of metabolic and
      oxidative stresses in tumorigenesis.
AB  - Tumorigenesis is always concomitant with microenvironmental alterations. The
      tumor microenvironment is a heterogeneous and complex milieu, which exerts a
      variety of stresses on tumor cells for proliferation, survival, or death.
      Recently, accumulated evidence revealed that metabolic and oxidative stresses
      both play significant roles in tumor development and progression that converge on
      a common autophagic pathway. Tumor cells display increased metabolic autonomy,
      and the hallmark is the exploitation of aerobic glycolysis (termed Warburg
      effect), which increased glucose consumption and decreased oxidative
      phosphorylation to support growth and proliferation. This characteristic renders
      cancer cells more aggressive; they devour tremendous amounts of nutrients from
      microenvironment to result in an ever-growing appetite for new tumor vessel
      formation and the release of more "waste," including key determinants of cell
      fate like lactate and reactive oxygen species (ROS). The intracellular ROS level
      of cancer cells can also be modulated by a variety of stimuli in the tumor
      microenvironment, such as pro-growth and pro-inflammatory factors. The
      intracellular redox state serves as a double-edged sword in tumor development and
      progression: ROS overproduction results in cytotoxic effects and might lead to
      apoptotic cell death, whereas certain level of ROS can act as a second-messenger
      for regulation of such cellular processes as cell survival, proliferation, and
      metastasis. The molecular mechanisms for cancer cell responses to metabolic and
      oxidative stresses are complex and are likely to involve multiple molecules or
      signaling pathways. In addition, the expression and modification of these
      proteins after metabolic or oxidative stress challenge are diverse in different
      cancer cells and endow them with different functions. Therefore, MS-based high
      throughput platforms, such as proteomics, are indispensable in the global
      analysis of cancer cell responses to metabolic and oxidative stress. Herein, we
      highlight recent advances in the understanding of the metabolic and oxidative
      stresses associated with tumor progression with proteomics-based systems biology
      approaches.

PMID- 23165950
TI  - Recurrence of hepatitis C virus infection during pityriasis rosea.

PMID- 23165951
TI  - A stress MRI of the shoulder for evaluation of ligamentous stabilizers in acute
      and chronic acromioclavicular joint instabilities.
AB  - PURPOSE: To show the feasibility of a stress magnetic resonance imaging (MRI) as
      a new method for simultaneous evaluation of the morphology and the functional
      integrity of the acromioclavicular joint (ACJ) ligamentous stabilizers. MATERIALS
      AND METHODS: MRI of four volunteers, 10 patients with acute, and six with chronic
      ACJ injuries was performed using a 0.25 T open MRI scanner. A 2D-proton-density
      and a 3D-gradient-echo sequence at rest and under 6.5 kg shoulder traction were
      performed. Comparative measurements of the coracoclavicular and the
      acromioclavicular distance were performed. Additionally, the conoid and trapezoid
      ligament lengths were measured with multiplanar reconstructions. RESULTS: MRI at
      rest correctly identified tears of the coracoclavicular and the acromioclavicular
      ligaments in eight patients suffering acute ACJ injuries. Stress application
      helped to distinguish between partial and complete coracoclavicular ligament
      tears in two cases. Insufficiency of the ACJ ligaments was present in all acute
      and chronic ACJ injuries. Stress application in chronic ACJ ligaments revealed
      isolated insufficiency of the conoid ligament in three cases and of the trapezoid
      ligament in one case. Combined insufficiency was present in two cases.
      CONCLUSION: Stress MRI facilitates simultaneous acquisition of morphologic and
      functional information of the ACJ stabilizers. In acute ACJ injuries it helps to
      distinguish between partial and complete ligament tears. In chronic ACJ injuries
      it provides functional information of the ligament regrinds.

PMID- 23165952
TI  - Lower fracture risk in older men with higher sclerostin concentration: a
      prospective analysis from the MINOS study.
AB  - Sclerostin is synthesized by osteocytes and inhibits bone formation. We measured
      serum sclerostin levels in 710 men aged 50 years and older. Bone mineral density
      (BMD) was measured at the lumbar spine, hip, and distal forearm. Serum sclerostin
      increased with age (unadjusted r = 0.30, p < 0.001). After adjustment for age,
      weight, and bioavailable 17beta-estradiol, serum sclerostin correlated positively
      with BMD (r = 0.24 to 0.35, p < 0.001) and negatively with the levels of bone
      turnover markers (r = - 0.09 to - 0.23, p < 0.05 to 0.001). During a 10-year
      follow-up, 75 men sustained fragility fractures. Fracture risk was lower in the
      two upper quintiles of sclerostin combined versus three lower quintiles combined
      (6.1 versus 13.5%, p < 0.01). We compared fracture risk in the two highest
      quintiles combined versus three lower quintiles combined using the Cox model
      adjusted for age, weight, leisure physical activity, BMD, bone width (tubular
      bones), prevalent fracture, prevalent falls, ischemic heart disease, and severe
      abdominal aortic calcification. Men with higher sclerostin concentration had
      lower fracture risk (adjusted for hip BMD, hazard ratio [HR] = 0.55, 95%
      confidence interval [CI] 0.31 to 0.96, p < 0.05). The results were similar in 47
      men with major fragility fractures (adjusted for lumbar spine BMD: HR = 0.39, 95%
      CI 0.17 to 0.90, p < 0.05). Men who had higher sclerostin and higher BMD (two
      highest quintiles) had lower risk of fracture compared with men who had lower BMD
      and lower sclerostin levels (three lower quintiles) (HR = 0.24, 95% CI 0.10 to
      0.62, p < 0.005). Circulating sclerostin was not associated with mortality rate
      or the incidence of major cardiovascular events. Thus, in older men, higher serum
      sclerostin levels are associated with lower risk of fracture, higher BMD, and
      lower bone turnover rate.

PMID- 23165953
TI  - Increased risk of breast cancer in women with NF1.
AB  - Neurofibromatosis type 1 (NF1) is a common autosomal dominant disorder associated
      with increased risk for neoplasms. Two studies in the United Kingdom have
      indicated that women with NF1 (particularly women under 50) may also be at
      increased risk of breast cancer. No such study has been done to date in the
      United States. Chart review for breast cancer diagnoses was undertaken for 126
      women with NF1 followed at Johns Hopkins who were 20 years of age or older. Four
      of 126 women who met eligibility criteria were diagnosed with breast cancer (3.2%
      over 15 years). The unadjusted standardized incidence ratio (SIR) for breast
      cancer in the NF1 population between the ages of 20 and 49 was 2.68 (P = 0.076,
      95% CI 0.68-7.29) based on incidence rates of breast cancer in the general
      population taken from the Surveillance Epidemiology and End Results (SEER)
      database. The unadjusted SIR for women with NF1 >=50 was 0.81 (P = 0.84, 95% CI
      0.041-4.01). When adjusted for race, the rate of NF1 in the general population
      and time of diagnosis, the SIR was 4.41 (P = 0.0049, 95% CI 1.12-12.00) for women
      <50 versus 0.94 (P = 0.95, 95% CI 0.047-4.65) for women >=50. The trend of a
      higher-than-expected number of breast cancer cases in women <50 with NF1 agrees
      with the prior studies from the literature. Cumulatively, the data suggests an
      increased risk of breast cancer for women with NF1 < 50 years old, implying a
      need for closer surveillance and the establishment of screening guidelines for
      this patient population.

PMID- 23165954
TI  - Structure of the high-pressure phase IV of KH2PO4 (KDP).
AB  - The high-pressure phase IV of potassium dihydrogen phosphate (KH(2)PO(4), KDP)
      has been determined at 1.62 GPa/296 K. It is monoclinic, space group P2(1)/c, Z =
      12, and on decompression transforms into monoclinic phase I. The interplay of
      OH...O bonding networks and K(+) coordination types leads to an exceptionally
      large number of KDP polymorphs, at least 13 according to the literature.

PMID- 23165955
TI  - Differential gene expression profiles in spontaneously hypertensive rats induced
      by administration of enalapril and nifedipine.
AB  - Enalapril and nifedipine are used as antihypertensive drugs; however, the
      therapeutic target molecules regulated by enalapril and nifedipine have yet to be
      fully identified. The aim of this study was to identify novel target genes that
      are specifically regulated by enalapril and nifedipine in tissues from
      spontaneously hypertensive rats (SHR) using DNA microarray analysis. We found
      that administration of SHR with enalapril and nifedipine differentially regulated
      33 genes involved in the pathogenesis of cardiovascular diseases. Furthermore, we
      identified 16 genes that have not previously been implicated in cardiovascular
      diseases, including interleukin-24 (IL-24). Among them, exogenous administration
      of IL-24 attenuated the expression of vascular inflammation and hypertension
      related genes induced by H2O2 treatment in mouse vascular smooth muscle (MOVAS)
      cells. This study provides valuable information for the development of novel
      antihypertensive drugs. In addition, the genes identified may be of use as
      biomarkers and therapeutic targets for cardiovascular diseases, including
      hypertension.

PMID- 23165956
TI  - Zolpidem is independently associated with increased risk of inpatient falls.
AB  - BACKGROUND: Inpatient falls are associated with significant morbidity and
      increased healthcare costs. Zolpidem has been reported to decrease balance and is
      associated with falls. Yet, it is a commonly used hypnotic agent in the inpatient
      setting. Zolpidem use in hospitalized patients may be a significant and
      potentially modifiable risk factor for falling. OBJECTIVE: To determine whether
      inpatients administered zolpidem are at greater risk of falling. DESIGN:
      Retrospective cohort study. SETTING: Adult non-intensive care unit (non-ICU)
      inpatients at a tertiary care center. METHODS: Adult inpatients who were
      prescribed zolpidem were identified. Electronic medical records were reviewed to
      capture demographics and other risk factors for falls. The fall rate was compared
      in those administered zolpidem versus those only prescribed zolpidem.
      Multivariate analyses were performed to determine whether zolpidem was
      independently associated with falls. RESULTS: The fall rate among patients who
      were prescribed and received zolpidem (n = 4962) was significantly greater than
      among patients who were prescribed but did not receive zolpidem (n = 11,358)
      (3.04% vs 0.71%; P < 0.001). Zolpidem use continued to remain significantly
      associated with increased fall risk after accounting for age, gender, insomnia,
      delirium status, dose of zolpidem, Charlson comorbidity index, Hendrich's fall
      risk score, length of hospital stay, presence of visual impairment, gait
      abnormalities, and dementia/cognitive impairment (adjusted odds ratio [OR] 4.37,
      95% confidence interval [CI] = 3.34-5.76; P < 0.001). Additionally, patients
      taking zolpidem who experienced a fall did not differ from other hospitalized
      adult patients who fell in terms of age, opioids, antidepressants, sedative
      antidepressants, antipsychotics, benzodiazepine, or antihistamine use.
      CONCLUSION: Zolpidem use was a strong, independent, and potentially modifiable
      risk factor for inpatient falls.

PMID- 23165958
TI  - WONCA Europe in Vienna 2012--what have we learned?

PMID- 23165957
TI  - Parkinson's disease duration determines effect of dopaminergic therapy on ventral
      striatum function.
AB  - We investigated the hypothesis that variation in endogenous dopamine (DA) across
      brain regions explains dissimilar effects of dopaminergic therapy on aspects of
      cognition in early Parkinson's disease (PD). Extensive degeneration of DA
      producing cells in the substantia nigra cause dorsal striatum (DS) DA deficiency
      and movement abnormalities. Particularly in early PD, this contrasts with
      relative sparing of the dopaminergic cells of the ventral tegmental area (VTA).
      The hypothesis predicts that DS-mediated cognitive functions are deficient at
      baseline and improved by DA replacement, whereas functions depending upon VTA
      innervated brain regions are normal off medication and worsen with treatment. The
      latter pattern presumably owes to overdose of relatively DA-replete VTA-supplied
      brain regions with medication levels titrated to DS-mediated motor symptoms. As
      PD progresses, however, VTA degeneration increases. Impairment in cognitive
      operations performed by VTA-innervated brain regions, such as the ventral
      striatum (VS), is expected. We compared the performance of early and late PD
      patients, on and off dopaminergic medication, relative to age-matched controls,
      on reward learning, previously shown to implicate the VS. As expected, in early
      PD, stimulus-reward learning was normal off medication, but worsened with DA
      replacement. At more advanced disease stages, PD patients learned stimulus-reward
      contingencies more poorly than controls and early PD patients off medication.
      Furthermore, dopaminergic medication did not worsen reward learning in late PD
      patients, in line with the dopamine overdose hypothesis. Unlike its effect on DS
      mediated functions, however, DA-replacement therapy did not improve reward
      learning in late PD patients.

PMID- 23165960
TI  - Electroacupuncture exerts anti-inflammatory effects in cerebral ischemia
      reperfusion injured rats via suppression of the TLR4/NF-kappaB pathway.
AB  - Inflammatory response has been shown to play a critical role in brain damage
      after cerebral ischemia-reperfusion (I/R) injury, which is tightly regulated by
      the Toll-like receptor (TLR)4/nuclear factor (NF)-kappaB pathway; therefore,
      suppression of TLR4/NF-kappaB signaling has become a promising target for the
      anti-inflammatory treatment in ischemic stroke. Acupuncture has been used as a
      complementary and alternative therapy practice that supplements conventional
      medicine. Numerous studies have demonstrated the clinical efficacy of acupuncture
      in stroke rehabilitation. However, the precise mechanism of its neuroprotective
      effect remains poorly understood. Using a focal cerebral I/R injured rat model,
      in the present study we evaluated the neuroprotective and anti-inflammatory
      activities of electroacupuncture at Quchi and Zusanli, and investigated the
      underlying molecular mechanisms. We found that electroacupuncture at Quchi (LI11)
      and Zusanli (ST36) acupoints significantly improved the ischemia-associated
      scores of neurological deficits, reduced cerebral infarction and alleviated
      inflammatory responses. Moreover, the crucial signaling molecules in the TLR4/NF
      kappaB signaling pathway were regulated by acupuncture, which coincided with
      suppressed secretion levels of inflammatory cytokines such as TNF-alpha, IL-1beta
      and IL-6. Our data suggest that electroacupuncture exerts a neuroprotective
      function in ischemic stroke through inhibition of TLR4/NF-kappaB-mediated
      inflammation.

PMID- 23165961
TI  - Effects of Acer okamotoanum sap on the function of polymorphonuclear neutrophilic
      leukocytes in vitro and in vivo.
AB  - Sap is a plant fluid that primarily consists of water and small amounts of
      mineral elements, sugars, hormones and other nutrients. Acer mono (A. mono) is an
      endemic Korean mono maple which was recently suggested to have health benefits
      due to its abundant calcium and magnesium ion content. In the present study, we
      examined the effects of sap from Acer okamotoanum (A. okamotoanum) on the
      phagocytic response of mouse neutrophils in vivo and rat and canine neutrophils
      in vitro. We tested the regulation of phagocytic activity, oxidative burst
      activity (OBA) and the levels of filamentous polymeric actin (F-actin) in the
      absence and presence of dexamethasone (DEX) in vitro and in vivo. Our results
      showed that DEX primarily reduced OBA in the mouse neutrophils, and that this was
      reversed in the presence of the sap. By contrast, the phagocytic activity of the
      mouse cells was not regulated by either DEX or the sap. Rat and canine
      polymorphonuclear neutrophilic leukocytes (PMNs) responded in vitro to the sap in
      a similar manner by increasing OBA. However, regulation of phagocytic activity by
      the sap was different between the species. In canine PMNs, phagocytic activity
      was enhanced by the sap at a high dose, while it did not significantly modulate
      this activity in rat PMNs. These findings suggest that the sap of A. okamotoanum
      stimulates neutrophil activity in the mouse, rat and canine by increasing OBA in
      vivo and in vitro, and thus may have a potential antimicrobial effect in the PMNs
      of patients with infections.

PMID- 23165962
TI  - Application of mass spectrometry to hair analysis for forensic toxicological
      investigations.
AB  - The increasing role of hair analysis in forensic toxicological investigations
      principally owes to recent improvements of mass spectrometric instrumentation.
      Research achievements during the last 6 years in this distinctive application
      area of analytical toxicology are reviewed. The earlier state of the art of hair
      analysis was comprehensively covered by a dedicated book (Kintz, 2007a.
      Analytical and practical aspects of drug testing in hair. Boca Raton: CRC Press
      and Taylor & Francis, 382 p) that represents key reference of the present
      overview. Whereas the traditional organization of analytical methods in forensic
      toxicology divided target substances into quite homogeneous groups of drugs, with
      similar structures and chemical properties, the current approach often takes
      advantage of the rapid expansion of multiclass and multiresidue analytical
      procedures; the latter is made possible by the fast operation and extreme
      sensitivity of modern mass spectrometers. This change in the strategy of
      toxicological analysis is reflected in the presentation of the recent literature
      material, which is mostly based on a fit-for-purpose logic. Thus, general
      screening of unknown substances is applied in diverse forensic contexts than
      drugs of abuse testing, and different instrumentation (triple quadrupoles, time
      of-flight analyzers, linear and orbital traps) is utilized to optimally cope with
      the scope. Other key issues of modern toxicology, such as cost reduction and high
      sample throughput, are discussed with reference to procedural and instrumental
      alternatives.

PMID- 23165963
TI  - Scores of scores.

PMID- 23165964
TI  - Effect of formalin fixation on biexponential modeling of diffusion decay in
      prostate tissue.
AB  - PURPOSE: To evaluate the effect of formalin fixation on biexponential modeling of
      diffusion decay in prostate tissue. METHODS: Three whole prostate specimens were
      imaged unfixed immediately postsurgery, and again after formalin fixation.
      Diffusion-weighted imaging was performed over an extended range of b-values and a
      biexponential model fitted to the signal decay curves. RESULTS: Tissue fixation
      resulted in a 35%, 20%, and 20% reduction in mean apparent diffusion coefficient
      of the higher diffusivity fit component for the three organs, respectively, and a
      64%, 57%, and 45% reduction in mean apparent diffusion coefficient of the lower
      diffusivity component. The mean signal fraction of the higher diffusivity
      component was increased by 23%, 5%, and 1%, respectively. The effect of fixation
      did not appear to vary according to tissue type or glandular zone. CONCLUSION:
      Formalin fixed tissue appears to provide a stable model for detailed
      investigation of the microscopic biophysical basis of diffusion phenomena
      observed in vivo. Diffusivity changes that result from fixation may provide
      information about the microscopic environments of the biexponential components.

PMID- 23165965
TI  - Sex-specific consequences of experimental cortisol elevation in pre-reproductive
      wild largemouth bass.
AB  - Experimental implants were used to investigate the effect of elevated cortisol
      (the primary stress hormone in teleost fish) on energetic and physiological
      condition prior to reproduction in male and female largemouth bass (Micropterus
      salmoides). Fish were wild-caught from lakes in Illinois, and held in
      experimental ponds for the duration of the study. Between 9 and 13 days after
      cortisol treatment, and immediately prior to the start of the reproductive
      period, treated and control animals were sampled. Females exhibited lower muscle
      lipid content, lower liver glycogen content, and higher hepatosomatic indices
      than males, regardless of treatment. Also, cortisol-treated females had higher
      hepatosomatic indices and lower final mass than control females, whereas males
      showed no differences between treatment groups. Finally, cortisol-treated females
      had higher gonadal cortisol concentrations than control females. In general, we
      found evidence of reduced energetic stores in female fish relative to male fish,
      likely due to timing differences in the allocation of resources during
      reproduction between males and females. Perhaps driven by the difference in
      energetic reserves, our data further suggest that females are more sensitive than
      males to elevated cortisol during the period immediately prior to reproduction.

PMID- 23165966
TI  - Mosaic 18q21.2 deletions including the TCF4 gene: a clinical report.
AB  - Pitt-Hopkins syndrome (PTHS) is characterized by distinctive facial dysmorphism,
      profound intellectual disability, and the possible occurrence of epilepsy and
      breathing anomalies. It is caused by haploinsufficiency of the TCF4 gene. No
      significant difference in clinical severity has been reported to date between
      PTHS patients carrying 18q21 deletions including the TCF4 gene, and those
      harboring TCF4 point mutations, suggesting a lack of genotype/phenotype
      correlation. Moreover, the size of 18q21 deletions including the TCF4 gene does
      not appear to have a significant effect on the phenotypic severity, suggesting
      that TCF4 haploinsufficiency is the most important prognostic factor in 18q
      deletions. We describe two unrelated patients presenting with clinical features
      reminiscent of PTHS and carrying mosaic interstitial 18q21 deletions
      characterized by array comparative genomic hybridization. One of the patients
      presented the lowest level of mosaic 18q21 deletion reported to date (5-10%). Our
      report and a review of the literature show that the mosaic status does not appear
      to have a significant effect on the clinical severity of 18q21 deletions, which
      are associated with a poor neurological outcome, whereas a mosaic TCF4 point
      mutation can result in a significantly milder phenotype. Malformations of
      internal organs are currently considered to be rare in PTHS. The patients
      described here had visceral anomalies, suggesting that a full morphological
      assessment, including heart and abdominal ultrasound scans, should be performed
      systematically in PTHS patients.

PMID- 23165967
TI  - Cool, or simple and cheap? Why not both?

PMID- 23165968
TI  - MRI tracking of transplanted iron-labeled mesenchymal stromal cells in an immune
      compromised mouse model of critical limb ischemia.
AB  - Peripheral arterial disease is a clinical problem in which mesenchymal stromal
      cell (MSC) transplantation may offer substantial benefit by promoting the
      generation of new blood vessels and improving limb ischemia and wound healing via
      their potent paracrine activities. MRI allows for the noninvasive tracking of
      cells over time using iron oxide contrast agents to label cells before they are
      injected or transplanted. However, a major limitation of the tracking of iron
      oxide-labeled cells with MRI is the possibility that dead or dying cells will
      transfer the iron oxide label to local bystander macrophages, making it very
      difficult to distinguish between viable transplanted cells and endogenous
      macrophages in the images. In this study, a severely immune-compromised mouse,
      with limited macrophage activity, was investigated to examine cell tracking in a
      system in which bystander cell uptake of dead, iron-labeled cells or free iron
      particles was minimized. MRI was used to track the fate of MSCs over 21 days
      after their intramuscular transplantation in mice with a femoral artery ligation.
      In all mice, a region of signal loss was observed at the injection site and the
      volume of signal hypointensity diminished over time. Fluorescence and light
      microscopy showed that iron-positive MSCs persisted at the transplant site and
      often appeared to be integrated in perivascular niches. This was compared with
      MSC transplantation in immune-competent mice with femoral artery ligation. In
      these mice, the regions of signal loss caused by iron-labeled MSC cleared more
      slowly, and histology revealed iron particles trapped at the site of cell
      transplantation and associated with areas of inflammation.

PMID- 23165969
TI  - Gate-induced modification of water adsorption on dielectrics probed by EFM and
      carbon nanotube FETs.
AB  - Humidity plays an important role in molecular electronics. It facilitates charge
      movement on top of dielectric layers and modifies the device transfer
      characteristics. Using two different methods to probe temporal charge
      redistribution on the surface of dielectrics, we were able to extract the surface
      humidity for the first time. The first method is based on the relaxation time
      constants of the current through carbon nanotube field-effect transistors
      (CNTFETs), and the second is based on electric force microscopy (EFM)
      measurements. Moreover, we found that applying external gate biases modifies the
      surface humidity. A theoretical model based on dielectrophoretic attraction
      between the water molecules and the substrate is introduced to explain this
      observation, and the results support our hypothesis. Furthermore, it is found
      that upon the adsorption of two to three layers of water the surface conductivity
      saturates.

PMID- 23165970
TI  - Direct tri-constituent co-assembly of highly ordered mesoporous carbon counter
      electrode for dye-sensitized solar cells.
AB  - Controlling over ordered porosity by self-assembly is challenging in the area of
      materials science. Materials with highly ordered aperture are favorable
      candidates in catalysis and energy conversion device. Here we describe a facile
      process to synthesize highly ordered mesoporous carbon (OMC) by direct tri
      constituent co-assembly method, which uses resols as the carbon precursor, tri
      block copolymer F127 as the soft template and tetraethoxysilane (TEOS) as the
      inorganic precursor. The obtained products are characterized by small-angle X-ray
      diffraction (SAXD), Brunauer-Emmett-Teller (BET) nitrogen sorption-desorption
      measurement and transmission electron microscope (TEM). The results indicate that
      the OMC possesses high surface areas of 1209 m(2) g(-1), homogeneous pore size of
      4.6 nm and a large pore volume of 1.65 cm(3) g(-1). The advantages of high
      electrochemical active surface area and favorable accessible porosity of OMC
      benefit the catalysis of I(3)(-) to I(-). As a result, the OMC counter electrode
      displays a remarkable property when it was applied in dye-sensitized solar cells
      (DSSCs). For comparison, carbon black (CB) counter electrode and Pt counter
      electrode have also been prepared. When these different counter electrodes were
      applied for dye-sensitized solar cells (DSSCs), the power-conversion efficiency
      (eta) of the DSSCs with CB counter electrode are measured to be 5.10%, whereas
      the corresponding values is 6.39% for the DSSC with OMC counter electrode, which
      is comparable to 6.84% of the cell with Pt counter electrode under the same
      experimental conditions.

PMID- 23165971
TI  - Stalking of psychiatrists: psychopathological characteristics and gender
      differences in an Italian sample.
AB  - Research has indicated that medical doctors and paramedics are at higher risk of
      being stalked than the general population. In particular, mental health care
      professionals alone represent one third of the victims of harassment. Because of
      the lack of studies in this specific sector, especially in Italy, in this study,
      we examined the stalking of psychiatrists by their patients, considering gender
      differences and the incidence of stalking in private practice and public mental
      health clinics in Rome. We found that the rate of stalking in private mental
      health settings is higher than that in public settings and that the perpetrators
      of stalking are mainly women who mostly target mental health professionals
      working in private practice. Implications of the findings are noted and
      discussed.

PMID- 23165972
TI  - (1) H magnetic resonance spectroscopy of neurodegeneration in a mouse model of
      niemann-pick type C1 disease.
AB  - PURPOSE: To evaluate brain metabolite levels as in vivo indicators of disease
      progression in a widely studied mouse model of Niemann-Pick type C1 (NPC1)
      disease with quantitative (1) H magnetic resonance spectroscopy (MRS). MATERIALS
      AND METHODS: Single voxel MRS experiments were carried out in vivo in a mouse
      model of NPC1 disease and in control mice in two brain regions (central and
      posterior) at two timepoints (presymptomatic and endstage) to examine changes in
      metabolite levels in NPC1 disease. Concentrations of nine metabolites were
      quantified by fitting a simulated basis set of metabolite signals to the acquired
      spectra. RESULTS: The only differences found in brain metabolite levels between
      NPC1 disease model and control mice were increased myo-inositol and decreased
      taurine in the posterior region of the brain at the endstage of the disease.
      Metabolite changes reported in past clinical MRS studies of NPC disease were not
      found in the current study of the mouse model. CONCLUSIONS: The (1) H spectra
      obtained from NPC1 mice and control mice were very similar, even at endstages of
      the disease. Although differences in two metabolites associated with
      neurodegenerative diseases were found and could inform future studies of the
      disease model, it appears that MRS in this mouse model of NPC1 disease does not
      have the sensitivity desired for a biomarker.

PMID- 23165973
TI  - Fast direct fourier reconstruction of radial and PROPELLER MRI data using the
      chirp transform algorithm on graphics hardware.
AB  - PURPOSE: To develop and test a new algorithm for fast direct Fourier transform
      (DrFT) reconstruction of MR data on non-Cartesian trajectories composed of lines
      with equally spaced points. THEORY AND METHODS: The DrFT, which is normally used
      as a reference in evaluating the accuracy of other reconstruction methods, can
      reconstruct images directly from non-Cartesian MR data without interpolation.
      However, DrFT reconstruction involves substantially intensive computation, which
      makes the DrFT impractical for clinical routine applications. In this article,
      the Chirp transform algorithm was introduced to accelerate the DrFT
      reconstruction of radial and Periodically Rotated Overlapping ParallEL Lines with
      Enhanced Reconstruction (PROPELLER) MRI data located on the trajectories that are
      composed of lines with equally spaced points. The performance of the proposed
      Chirp transform algorithm-DrFT algorithm was evaluated by using simulation and in
      vivo MRI data. RESULTS: After implementing the algorithm on a graphics processing
      unit, the proposed Chirp transform algorithm-DrFT algorithm achieved an
      acceleration of approximately one order of magnitude, and the speed-up factor was
      further increased to approximately three orders of magnitude compared with the
      traditional single-thread DrFT reconstruction. CONCLUSION: Implementation the
      Chirp transform algorithm-DrFT algorithm on the graphics processing unit can
      efficiently calculate the DrFT reconstruction of the radial and PROPELLER MRI
      data.

PMID- 23165974
TI  - Pitch variability in patients with Parkinson's disease: effects of deep brain
      stimulation of caudal zona incerta and subthalamic nucleus.
AB  - PURPOSE: The purpose of the present study was to examine the effect of deep brain
      stimulation (DBS) of the subthalamic nucleus (STN) and the caudal zona incerta
      (cZi) pitch characteristics of connected speech in patients with Parkinson's
      disease (PD). METHOD: The authors evaluated 16 patients preoperatively and 12
      months after DBS surgery. Eight patients were implanted in the STN (ages 51-72
      years;   M = 63 years). Six received bilateral implantation and 2 unilateral
      (left) implantation. Eight patients were bilaterally implanted in the cZi (ages
      49-71 years;   M = 60.8 years). Preoperative assessments were made after a
      levodopa challenge (approximately 1.5 times the ordinary dose). All postoperative
      examinations were made off and on stimulation with a clinically optimized dose of
      levodopa. Measurements of pitch range and variability were obtained from each
      utterance in a recorded read speech passage. RESULTS: Pitch range and coefficient
      of variation showed an increase in patients under STN-DBS. Patients under cZi-DBS
      showed no significant effects of treatment on investigated pitch properties.
      CONCLUSION: STN-DBS was shown to increase pitch variation and range. The results
      provided no evidence of cZi-DBS having a beneficial effect on PD patients' pitch
      variability.

PMID- 23165975
TI  - Further evidence of auditory extinction in aphasia.
AB  - PURPOSE: Preliminary research (Shisler, 2005) suggests that auditory extinction
      in individuals with aphasia (IWA) may be connected to binding and attention. In
      this study, the authors expanded on previous findings on auditory extinction to
      determine the source of extinction deficits in IWA. METHOD: Seventeen IWA (M(age)
      = 53.19 years) and 17 neurologically intact controls (M(age) = 55.18 years)
      participated. Auditory stimuli were spoken letters presented in a free-field
      listening environment. Stimuli were presented in single-stimulus stimulation
      (SSS) or double-simultaneous stimulation (DSS) trials across 5 conditions
      designed to determine whether extinction is related to binding, inefficient
      attention resource allocation, or overall deficits in attention. All participants
      completed all experimental conditions. RESULTS: Significant extinction was
      demonstrated only by IWA when sounds were different, providing further evidence
      of auditory extinction. However, binding requirements did not appear to influence
      the IWA's performance. CONCLUSIONS: Results indicate that, for IWA, auditory
      extinction may not be attributed to a binding deficit or inefficient attention
      resource allocation because of equivalent performance across all 5 conditions.
      Rather, overall attentional resources may be influential. Future research in
      aphasia should explore the effect of the stimulus presentation in addition to the
      continued study of attention treatment.

PMID- 23165976
TI  - Real-time cell viability assays using a new anthracycline derivative DRAQ7(r).
AB  - The exclusion of charged fluorescent dyes by intact cells has become a well
      established assay for determining viability of cells. In search for a noninvasive
      fluorescent probe capable of long-term monitoring of cell death in real-time, we
      evaluated a new anthracycline derivative DRAQ7. The novel probe does not
      penetrate the plasma membrane of living cells but when the membrane integrity is
      compromised, it enters and binds readily to nuclear DNA to report cell death. It
      proved to be nontoxic to a panel of cancer cell lines grown continuously for up
      to 72 h and did not induce any detectable DNA damage signaling when analyzed
      using laser scanning microscopy and flow cytometry. The DRAQ7 provided a
      sensitive, real-time readout of cell death induced by a variety of stressors such
      as hypoxia, starvation, and drug-induced cytotoxicity. The overall responses to
      anticancer agents and resulting pharmacological dose-response profiles were not
      affected by the growth of tumor cells in the presence DRAQ7. Moreover, we for the
      first time introduced a near real-time microflow cytometric assay based on
      combination of DRAQ7 and mitochondrial inner membrane potential (DeltaPsi(m) )
      sensitive probe TMRM. We provide evidence that this low-dosage, real-time
      labeling procedure provides multiparameter and kinetic fingerprint of anticancer
      drug action.

PMID- 23165977
TI  - Management of the axilla in early breast cancer patients in the genomic era.
AB  - Management of the axilla in early breast cancer (EBC) patients has dramatically
      evolved in recent years from more radical to increasingly conservative
      approaches. Classically, the EBC patients with a clinically positive axilla are
      offered axillary lymph node dissection (ALND) and those with a clinically
      negative axilla (cN0) are offered sentinel lymph node (SLN) biopsy, which
      obviates the complications related to ALND and provides adequate surgical staging
      and comparable locoregional control and survival. The need for performing ALND
      when the SLN is positive and contemporary adjuvant treatment is delivered has
      been questioned in recent years. On the other hand, ongoing trials are testing
      whether node-positive patients can be spared chemotherapy, based on intrinsic
      primary tumor biology. Because the integration of novel surgical management and
      tumor biology is needed, this article provides an overview of the current
      challenges that a more detailed knowledge of tumor biology has brought to EBC
      staging and treatment. We propose that breast cancer oncologists (surgeons,
      radiation therapists, and medical oncologists) should focus their efforts on
      offering therapy tailored to each patient's needs in such a way that no matter
      which treatment is used, no overtreatment occurs.

PMID- 23165979
TI  - Construction of a novel oncolytic adenoviral vector and its biological
      characteristics.
AB  - In this study, we aimed to construct an effective and safe oncolytic adenoviral
      vector for cancer treatment with gene therapy. First, the promoter of the
      catalytic subunit of human telomerase (hTERTp), adenovirus early region 1a gene
      (E1A) and thymidine kinase gene of human herpes virus type 1 (HSV-1-TK) were
      amplified by using PCR from genomic DNA of 293A cells and wild-type HSV-1 (wHSV
      1). These specially-prepared elements were inserted into an adenoviral shuttle
      vector in the opposite and the same directions of left inverted terminal repeat
      (L-ITR), respectively, to construct pENTR-E1A-IRES-TK-hTERTp (pEITH) and pENTR
      hTERTp-E1A-IRES-TK (pHEIT). LR reaction between adenoviral shuttle vectors (pEITH
      and pHEIT) and the backbone vector DEST was carried out to establish adenoviral
      expression vectors pAd-E1A-IRES-TK-hTERTp (pAd-EITH) and pAd-hTERTp-E1A-IRES-TK
      (pAd-HEIT). Recombinant adenovirus Ad-EITH and Ad-HEIT were produced by
      transfecting 293A cells and purified for the subsequent studies of titer
      measurement, replication capability with and without acyclovir (ACV) and
      antitumor ability with and without ganciclovir (GCV) to evaluate the biological
      characteristics. Adenoviral shuttle vectors pEITH and pHEIT and expression
      vectors pAd-EITH and pAd-HEIT were successfully constructed, and recombinant
      adenoviruses Ad-EITH and Ad-HEIT with high titer were produced. The results of
      replication and cytotoxicity assays showed that Ad-EITH and Ad-HEIT replicated in
      the hTERTp (+) human nasopharyngeal carcinoma cell line CNE and expressed the TK
      gene effectively leading to the death of tumor cells. In addition, there were
      still some Ad-HEIT particles replicating in the hTERTp (-) human osteosarcoma U
      2OS cells and human lung HFL-1 fibroblasts compared to Ad-EITH which was hardly
      able to replicate in U-2OS and HFL-1 cells. In addition, we also observed an
      interesting phenomenon, that the replication of Ad-EITH could be inhibited by
      antiviral drug ACV on account of the expression of HSV-1-TK gene making Ad-EITH
      sensitive to ACV. In conclusion, a novel oncolytic adenoviral vector Ad-EITH was
      produced which can be used for cancer-specific and efficient viral replication,
      and its safety is potentially improved as replication can be inhibited by ACV in
      vitro.

PMID- 23165978
TI  - Coagulase-negative staphylococci as reservoirs of genes facilitating MRSA
      infection: Staphylococcal commensal species such as Staphylococcus epidermidis
      are being recognized as important sources of genes promoting MRSA colonization
      and virulence.
AB  - Recent research has suggested that Staphylococcus epidermidis is a reservoir of
      genes that, after horizontal transfer, facilitate the potential of Staphylococcus
      aureus to colonize, survive during infection, or resist antibiotic treatment,
      traits that are notably manifest in methicillin-resistant S. aureus (MRSA). S.
      aureus is a dangerous human pathogen and notorious for acquiring antibiotic
      resistance. MRSA in particular is one of the most frequent causes of morbidity
      and death in hospitalized patients. S. aureus is an extremely versatile pathogen
      with a multitude of mechanisms to cause disease and circumvent immune defenses.
      In contrast, most other staphylococci, such as S. epidermidis, are commonly
      benign commensals and only occasionally cause disease. Recent findings highlight
      the key importance of efforts to better understand how genes of staphylococci
      other than S. aureus contribute to survival in the human host, how they are
      transferred to S. aureus, and why this exchange appears to be uni-directional.

PMID- 23165980
TI  - Patterns of survival in lymphoplasmacytic lymphoma/Waldenstrom macroglobulinemia:
      a population-based study of 1,555 patients diagnosed in Sweden from 1980 to 2005.
AB  - Clinical management of lymphoplasmacytic lymphoma (LPL)/Waldenstrom
      macroglobulinemia (WM) has changed considerably over recent years, reflected in
      the use of new therapeutic agents (purine analogs, monoclonal antibodies,
      thalidomide- and bortezomib-based therapies). No population-based studies and few
      randomized trials have been performed to assess survival in newly diagnosed
      LPL/WM. We performed a large population-based study in Sweden including 1,555
      LPL/WM patients diagnosed from 1980 to 2005. Relative survival ratios (RSRs) and
      excess mortality rate ratios (EMRR) were computed as measures of survival.
      Survival of LPL/WM patients has improved significantly (P = 0.007) over time with
      5-year RSR = 0.57 (95% confidence interval [CI] 0.46-0.68), 0.65 (0.57-0.73),
      0.74 (0.68-0.80), 0.72 (0.66-0.77), and 0.78 (0.71-0.85) for patients diagnosed
      during the calendar periods 1980-1985, 1986-1990, 1991-1995, 1996-2000, and 2001
      2005, respectively. Improvement in 1- and 5-year relative survival was found in
      all age groups and for LPL and WM separately. Patients with WM had lower excess
      mortality compared to LPL (EMRR = 0.38; 95% CI 0.30-0.48). Older age at diagnosis
      was associated with a poorer survival (P < 0.001). Taken together, we found a
      significant improvement in survival in LPL/WM over time. Despite this progress,
      new effective agents with a more favourable toxicity profile are needed to
      further improve survival in LPL/WM, especially in the elderly.

PMID- 23165981
TI  - Effectiveness of multidisciplinary care for Parkinson's disease: a randomized,
      controlled trial.
AB  - Multidisciplinary care is considered an optimal model to manage Parkinson's
      disease (PD), but supporting evidence is limited. We performed a randomized,
      controlled trial (RCT) to establish whether a multidisciplinary/specialist team
      offers better outcomes, compared to stand-alone care from a general neurologist.
      Patients with PD were randomly allocated to an intervention group (care from a
      movement disorders specialist, PD nurses, and social worker) or a control group
      (care from general neurologists). Both interventions lasted 8 months. Clinicians
      and researchers were blinded for group allocation. The primary outcome was the
      change in quality of life (Parkinson's Disease Questionnaire; PDQ-39) from
      baseline to 8 months. Other outcomes were the UPDRS, depression (Montgomery
      Asberg Depression Scale; MADRS), psychosocial functioning (Scales for Outcomes in
      Parkinson's disease-Psychosocial; SCOPA-PS), and caregiver strain (Caregiver
      Strain Index; CSI). Group differences were analyzed using analysis of covariance
      adjusted for baseline values and presence of response fluctuations. A total of
      122 patients were randomized and 100 completed the study (intervention, n = 51;
      control, n = 49). Compared to controls, the intervention group improved
      significantly on PDQ-39 (difference, 3.4; 95% confidence interval [CI]: 0.5-6.2)
      and UPDRS motor scores (4.1; 95% CI: 0.8-7.3). UPDRS total score (5.6; 95% CI:
      0.9-10.3), MADRS (3.7; 95% CI: 1.4-5.9), and SCOPA-PS (2.1; 95% CI: 0.5-3.7) also
      improved significantly. This RCT gives credence to a multidisciplinary/specialist
      team approach. We interpret these positive findings cautiously because of the
      limitations in study design. Further research is required to assess teams
      involving additional disciplines and to evaluate cost-effectiveness of integrated
      approaches. (c) 2012 Movement Disorder Society.

PMID- 23165983
TI  - Energy/hole transfer phenomena in hybrid alpha-sexithiophene (alpha-STH)
      nanoparticle-CdTe quantum-dot nanocomposites.
AB  - Considerable attention has been paid to hybrid organic-inorganic nanocomposites
      for designing new optical materials. Herein, we demonstrate the energy and hole
      transfer of hybrid hole-transporting alpha-sexithiophene (alpha-STH) nanoparticle
      CdTe quantum dot (QD) nanocomposites using steady-state and time-resolved
      spectroscopy. Absorption and photoluminescence studies confirm the loss of
      planarity of the alpha-sexithiophene molecule due to the formation of polymer
      nanoparticles. Upon photoexcitation at 370 nm, a nonradiative energy transfer (73
      %) occurs from the hole-transporting alpha-STH nanoparticles to the CdTe
      nanoparticles with a rate of energy transfer of 6.13*10(9) s(-1). However,
      photoluminescence quenching of the CdTe QDs in the presence of the hole
      transporting alpha-STH nanoparticles is observed at 490 nm excitation, which is
      due to both static-quenching and hole-transfer-based dynamic-quenching phenomena.
      The calculated hole-transporting rate is 7.13*10(7) s(-1) in the presence of
      42*10(-8)  M alpha-STH nanoparticles. Our findings suggest that the interest in
      alpha-sexithiophene (alpha-STH) nanoparticle-CdTe QD hybrid nanocomposites might
      grow in the coming years because of various potential applications, such as solar
      cells, optoelectronic devices, and so on.

PMID- 23165982
TI  - Involvement of Nrf2 activation in the upregulation of S100A9 by exposure to
      inorganic arsenite.
AB  - This study examined whether S100A8 and S100A9, which comprise a complex called
      calprotectin, are upregulated by exposure to sodium arsenite [As(III)] in nine
      lines of human-derived cells. HaCaT skin keratinocyte cells, U937 leukemic
      monocyte cells, and UROtsa urothelial cells showed increased mRNA levels of
      S100A8 and S100A9 after a 2-week exposure to As(III). To understand the
      mechanisms regulating S100A9 upregulation in response to As(III), we tested
      S100A9 promoter-dependent luciferase activity in HaCaT cells transfected with
      S100A9 promoter (-1000/+429)-fused luciferase cDNA. The results indicated that
      exposure to As(III) stimulated S100A9 promoter-dependent luciferase activity. In
      addition, the transcription NF-E2-related factor 2 (Nrf2) was strongly activated
      in HaCaT cells exposed to As(III). Since two putative antioxidant response
      elements were found in the S100A9 promoter (ARE1, 5'-ACAGGCAGGG-3' from -897 to 
      887; ARE2, 5'-ATCTTCCGGAG-3' from -78 to -67), we constructed deletion mutants of
      each ARE on S100A9 promoter-fused luciferase cDNA. The results indicated that
      ARE2 is the responsible element for the activation of S100A9 transcription in
      response to As(III). This report is the first to demonstrate that As(III)
      enhanced S100A8 and S100A9 expression in human-derived cells and As(III)-induced
      S100A9 expression is dependent on Nrf2 activation.

PMID- 23165984
TI  - Enzymatic amine acyl exchange in peptides on gold surfaces.
AB  - Reversible as well as stereo- and chemoselective: various proteases such as
      thermolysin and chymotrypsin catalyze amine acyl exchange in peptides. This acyl
      exchange can be used to modify amino-functionalized surfaces under physiological
      reaction conditions and provides an alternative mechanism for posttranslational
      transpeptidation reactions such as peptide-splicing reactions in the proteasome.

PMID- 23165985
TI  - Studies of the humoral factors produced by layered chondrocyte sheets.
AB  - The authors aimed to repair and regenerate articular cartilage with layered
      chondrocyte sheets, produced using temperature-responsive culture dishes. The
      purpose of this study was to investigate the humoral factors produced by layered
      chondrocyte sheets. Articular chondrocytes and synovial cells were harvested
      during total knee arthroplasty. After co-culture, the samples were divided into
      three groups: a monolayer, 7 day culture sheet group (group M); a triple-layered,
      7 day culture sheet group (group L); and a monolayer culture group with a cell
      count identical to that of group L (group C). The secretion of collagen type 1
      (COL1), collagen type 2 (COL2), matrix metalloproteinase-13 (MMP13), transforming
      growth factor-beta (TGFbeta), melanoma inhibitory activity (MIA) and
      prostaglandin E2 (PGE2) were measured by enzyme-linked immunosorbent assay
      (ELISA). Layered chondrocyte sheets produced the most humoral factors. PGE2
      expression declined over time in group C but was significantly higher in groups M
      and L. TGFbeta expression was low in group C but was significantly higher in
      groups M and L (p<0.05). Our results suggest that the humoral factors produced by
      layered chondrocyte sheets may contribute to cartilaginous tissue repair and
      regeneration.

PMID- 23165986
TI  - The Human Microbiome Project strategy for comprehensive sampling of the human
      microbiome and why it matters.
AB  - The Human Microbiome Project used rigorous good clinical practice standards to
      complete comprehensive body site sampling in healthy 18- to 40-yr-old adults,
      creating an unparalleled reference set of microbiome specimens. To ensure that
      specimens represented minimally perturbed microbiomes, we first screened
      potential participants using exclusion criteria based on health history,
      including the presence of systemic diseases (e.g., hypertension, cancer, or
      immunodeficiency or autoimmune disorders), use of potential immunomodulators, and
      recent use of antibiotics or probiotics. Subsequent physical examinations
      excluded individuals based on body mass index (BMI), cutaneous lesions, and oral
      health. We screened 554 individuals to enroll 300 (149 men and 151 women, mean
      age 26 yr, mean BMI 24 kg/m, 20.0% racial minority, and 10.7% Hispanic). We
      obtained specimens from the oral cavity, nares, skin, gastrointestinal tract, and
      vagina (15 specimens from men and 18 from women). The study evaluated
      longitudinal changes in an individual's microbiome by sampling 279 participants
      twice (mean 212 d after the first sampling; range 30-359 d) and 100 individuals 3
      times (mean 72 d after the second sampling; range 30-224 d). This sampling
      strategy yielded 11,174 primary specimens, from which 12,479 DNA samples were
      submitted to 4 centers for metagenomic sequencing. Our clinical design and well
      defined reference cohort has laid a foundation for microbiome research.

PMID- 23165987
TI  - Speech and hearing in adults with 22q11.2 deletion syndrome.
AB  - The purpose of the study was to investigate the prevalence of velopharyngeal
      impairment, compensatory articulation, reduced intelligibility, and to rate the
      general impression of speech in adults with 22q11.2 deletion syndrome. The second
      purpose was to study the prevalence and type of hearing impairment in these
      adults. A referred, consecutive series of 24 adults with confirmed 22q11.2
      deletion, 16 female and 8 males, with a mean age of 25 years (19-38 years) was
      included in the study. A blind assessment of speech by three experienced speech
      language pathologists was performed. Sixteen (66%) patients had a mild to severe
      velopharyngeal impairment. The most prevalent symptoms of velopharygeal
      impairment were hypernasality and audible nasal airflow. The mean nasalance score
      was 33% (6-66%). Only two patients had disordered articulation; one of these had
      glottal articulation. A mean of 96% (88-100%) of single words were rated to be
      intelligible. To achieve these results half of the patients previously had
      velopharyngeal flap surgery. Forty-one percent (9/22) had mild-moderate hearing
      impairment; three had sensorineural type, four conductive and two had a mixed
      type. In conclusion the majority of the patients had no articulation errors and
      good intelligibility; while one-third still had moderate to severe problems with
      velopharyngeal impairment. Around 40% still had some hearing impairment, in most
      cases with a mild to moderate conductive component. Thus, a high prevalence of
      speech and hearing problems seems to be a part of the phenotype in adults with
      22q11.2DS.

PMID- 23165988
TI  - Classification of breast lesions pre-contrast injection using water resonance
      lineshape analysis.
AB  - Inhomogeneously broadened, non-Lorentzian water resonances have been observed in
      small image voxels of breast tissue. The non-Lorentzian components of the water
      resonance are probably produced by bulk magnetic susceptibility shifts caused by
      dense, deoxygenated tumor blood vessels (the 'blood oxygenation level-dependent'
      effect), but can also be produced by other characteristics of local anatomy and
      physiology, including calcifications and interfaces between different types of
      tissue. Here, we tested the hypothesis that the detection of non-Lorentzian
      components of the water resonance with high spectral and spatial resolution
      (HiSS) MRI allows the classification of breast lesions without the need to inject
      contrast agent. Eighteen malignant lesions and nine benign lesions were imaged
      with HiSS MRI at 1.5 T. A new algorithm was developed to detect non-Lorentzian
      (or off-peak) components of the water resonance. After a Lorentzian fit had been
      subtracted from the data, the largest peak in the residual spectrum in each voxel
      was identified as the major off-peak component of the water resonance. The
      difference in frequency between these off-peak components and the main water
      peaks, and their amplitudes, were measured in malignant lesions, benign lesions
      and breast fibroglandular tissue. Off-peak component frequencies were
      significantly different between malignant and benign lesions (p < 0.001).
      Receiver operating characteristic (ROC) analysis was used to assess the
      diagnostic performance of HiSS off-peak component analysis compared with dynamic
      contrast-enhanced (DCE) MRI parameters. The areas under the ROC curves for the
      'DCE rapid uptake fraction', 'DCE washout fraction', 'off-peak component
      amplitude' and 'off-peak component frequency' were 0.75, 0.83, 0.50 and 0.86,
      respectively. These results suggest that water resonance lineshape analysis
      performs well in the classification of breast lesions without contrast injection
      and could improve the diagnostic accuracy of clinical breast MR examinations. In
      addition, this approach may provide an alternative to DCE MRI in women who are at
      risk for adverse reactions to contrast media.

PMID- 23165989
TI  - Neonatal brainstem function and 4-month arousal-modulated attention are jointly
      associated with autism.
AB  - The authors evaluated the contribution of initially abnormal neonatal auditory
      brainstem responses (ABRs) and 4-month arousal-modulated attention visual
      preference to later autism spectrum disorder (ASD) behaviors in neonatal
      intensive care unit (NICU) graduates. A longitudinal study design was used to
      compare NICU graduates with normal ABRs (n = 28) to those with initially abnormal
      ABRs (n = 46) that later resolved. At 4 months postterm age, visual preference
      (measured after feeding) for a random check pattern flashing at 1, 3, or 8 Hz and
      gestational age (GA) served as additional predictors. Outcome measures were PDD
      Behavior Inventory (PDDBI) scores at 3.4 years (standard deviation = 1.2), and
      developmental quotients (DQ) obtained around the same age with the Griffiths
      Mental Development Scales (GMDS). Preferences for higher rates of stimulation at
      4 months were highly correlated with PDDBI scores (all P-values < 0.01) and the
      GMDS Hearing and Speech DQ, but only in those with initially abnormal ABRs.
      Effects were strongest for a PDDBI social competence measure most associated with
      a diagnosis of autism. For those with abnormal ABRs, increases in preference for
      higher rates of stimulation as infants were linked to nonlinear increases in
      severity of ASD at 3 years and to an ASD diagnosis. Abnormal ABRs were associated
      with later reports of repetitive and ritualistic behaviors irrespective of 4
      month preference for stimulation. The joint occurrence of initially abnormal
      neonatal ABRs and preference for more stimulation at 4 months, both indices of
      early brainstem dysfunction, may be a marker for the development of autism in
      this cohort.

PMID- 23165990
TI  - Murine and human very small embryonic-like cells: a perspective.
AB  - In 2006, very small embryonic-like (VSEL) stem cells were described as a
      pluripotent population of prospectively isolated stem cells in adult murine bone
      marrow (mBM) and human umbilical cord blood (hUCB). While rigorous proof of
      pluripotency is still lacking, murine VSEL cells have been shown to overlap with
      an independently identified population of neural crest derived mesenchymal stem
      cells (MSC). The presence of primitive mesenchymal precursors within the VSEL
      cell population may partially explain the findings that have led to the concept
      of an "embryonic-like" stem cell in mBM. However, our own studies on human VSEL
      cells revealed very little similarity between murine VSEL cells and their
      reportedly equivalent population in hUCB. On the contrary, our data strongly
      suggest that human VSEL cells are an aberrant and inactive population that cannot
      expand in vitro and has neither embryonic nor adult stem cell like properties.
      Here we critically re-examine the data supporting stemness and pluripotency of
      murine and human VSEL cells, respectively.

PMID- 23165991
TI  - Bio-inspired magnetic swimming microrobots for biomedical applications.
AB  - Microrobots have been proposed for future biomedical applications in which they
      are able to navigate in viscous fluidic environments. Nature has inspired
      numerous microrobotic locomotion designs, which are suitable for propulsion
      generation at low Reynolds numbers. This article reviews the various swimming
      methods with particular focus on helical propulsion inspired by E. coli bacteria.
      There are various magnetic actuation methods for biomimetic and non-biomimetic
      microrobots, such as rotating fields, oscillating fields, or field gradients.
      They can be categorized into force-driven or torque-driven actuation methods.
      Both approaches are reviewed and a previous publication has shown that torque
      driven actuation scales better to the micro- and nano-scale than force-driven
      actuation. Finally, the implementation of swarm or multi-agent control is
      discussed. The use of multiple microrobots may be beneficial for in vivo as well
      as in vitro applications. Thus, the frequency-dependent behavior of helical
      microrobots is discussed and preliminary experimental results are presented
      showing the decoupling of an individual agent within a group of three
      microrobots.

PMID- 23165992
TI  - Selective detection of endotoxin using an impedance aptasensor with
      electrochemically deposited gold nanoparticles.
AB  - Using a single-stranded DNA (ssDNA) aptamer exhibiting high binding affinity (Kd
      = 12 nM) to endotoxin as a probe, an impedance sensor where aptamer-conjugated
      gold nanoparticles (AuNPs) were electrochemically deposited on a gold electrode
      was fabricated and its performance in regard to endotoxin detection assessed.
      AuNPs have been employed widely as biosensors because of their unique physical
      and chemical properties. In order to maximize the performance of the impedance
      aptasensor on endotoxin detection, some critical factors affecting aptamer
      conjugation to AuNPs and target recognition ability (i.e. concentrations of
      aptamer coupled with AuNPs, pH, ion strength and cation effect at the time of
      aptamer-endotoxin interaction) were optimized. Electrochemical impendence
      spectroscopy, cyclic voltametry, atomic force microscope, scanning electron
      microscope and quartz crystal microbalance were employed to characterize all the
      modification/detection procedures during the sensor fabrication. The developed
      aptasensor showed a broad linear dynamic detection range (0.01-10.24 ng/ml) with
      a very low detection limit for endotoxin (0.005 ng/ml), despite the presence of
      several biomolecules (e.g. plasmid DNA, RNA, serum albumin, Glc and sucrose)
      known to interfere with other endotoxin assays. The demonstrated aptasensor
      required a detection time of only 10 min, providing a simple and fast analytical
      method to specifically detect endotoxin from complex biological liqors. 

PMID- 23165993
TI  - Targeted biopsy based on ADC map in the detection and localization of prostate
      cancer: a feasibility study.
AB  - PURPOSE: To investigate the feasibility of targeted biopsy based on an apparent
      diffusion coefficient (ADC) map in the detection and localization of prostate
      cancer. MATERIALS AND METHODS: This study included 288 consecutive patients with
      high or increasing serum prostate-specific antigen (PSA) levels who underwent
      prostatic magnetic resonance imaging (MRI) examination with an ADC map. Four core
      targeted biopsies of low ADC lesions were performed under transrectal-ultrasound
      guidance with reference to ADC map. The positive predictive values (PPVs) of low
      ADC lesions were calculated and compared for the peripheral zone (PZ), transition
      zone (TZ), and anterior portion, respectively. Comparisons of ADC values and
      sizes between malignant and nonmalignant lesions were also performed. RESULTS: A
      total of 313 low ADC lesions were detected in 195 patients and sampled by
      targeted biopsies. The PPVs were 55.3% (95% confidence interval [CI]: 50-61) in
      total, 61.0% (95% CI: 53-69) for PZ, 50.6% (95% CI: 43-58) for TZ, and 90.9% (95%
      CI: 81-100) for the anterior portion. The most common nonmalignant pathology of
      low ADC lesions was hyperplasia, followed by chronic prostatitis. There were
      significant differences in ADC values and sizes between malignant and
      nonmalignant low ADC lesions. CONCLUSION: Targeted biopsies could be capable of
      detecting cancers well wherever they may be in the prostate, although the PPVs
      varied depending on the location of low ADC lesions.

PMID- 23165994
TI  - A new in vivo model to analyze hepatic metastasis of the human colon cancer cell
      line HCT116 in NOD/Shi-scid/IL-2Rgamma(null) (NOG) mice by (18)F-FDG PET/CT.
AB  - Clinically, (18)F-fluorodeoxyglucose positron emission tomography/computed
      tomography ((18)F-FDG-PET/CT) is useful in the evaluation of various types of
      human cancers. While PET analysis has been established to evaluate subcutaneous
      lesions of human cancers in mice, its applications for internal lesions are still
      being developed. We are currently evaluating new PET approaches for the effective
      evaluation of in vivo metastatic lesions in the internal organs of small
      experimental animals. In this study, we analyzed in vivo hepatic metastases of
      human colonic cancer in immunodeficient mice (NOD/Shi-scid/IL-2Rgamma(null), NOG)
      using PET imaging. This new PET approach has been proposed for the evaluation of
      in vivo metastatic lesions in internal organs. The human colon cancer line HCT116
      (1.0x10(5) and 1.0x10(6) cells/mouse) was transplanted by intrasplenic injection.
      (18)F-FDG-PET/CT scans were performed 2 weeks after transplantation. After PET/CT
      scans, histopathological examinations were performed. PET/CT analysis disclosed
      multiple metastatic foci and increased standardized uptake values (SUV) of FDG in
      the livers of NOG mice (control, SUVmean 0.450+/-0.033, SUVmax 0.635+/-0.017;
      1.0x10(5) cells, 0.853+/-0.087, 1.254+/-0.237; 1.0x10(6) cells, 1.211+/-0.108,
      1.701+/-0.158). There were significant differences in FDG uptakes between the
      three groups (ANOVA, P=0.017 in SUVmean; P=0.044 in SUVmax, n=2). We clearly and
      quantitatively detected images of hepatic metastasis in the livers of NOG mice by
      (18)F-FDG-PET/CT in vivo. PET/CT analysis of internal organ lesions of human
      cancerous xenografts is a new reliable experimental system to simulate
      metastases. This model system is useful for analyzing metastatic mechanisms and
      for developing new novel drugs targeting hepatic metastases of cancer.

PMID- 23165995
TI  - miRNAs, polyphenols, and chronic disease.
AB  - MicroRNAs (miRNAs) are small noncoding RNAs, approximately 18-25 nucleotides in
      length, that modulate gene expression at the posttranscriptional level. Thousands
      of miRNAs have been described, and it is thought that they regulate some aspects
      of more than 60% of all human cell transcripts. Several polyphenols have been
      shown to modulate miRNAs related to metabolic homeostasis and chronic diseases.
      Polyphenolic modulation of miRNAs is very attractive as a strategy to target
      numerous cell processes and potentially reduce the risk of chronic disease.
      Evidence is building that polyphenols can target specific miRNAs, such as miR
      122, but more studies are necessary to discover and validate additional miRNA
      targets.

PMID- 23165996
TI  - A circuit-based gatekeeper for adult neural stem cell proliferation: Parvalbumin
      expressing interneurons of the dentate gyrus control the activation and
      proliferation of quiescent adult neural stem cells.
AB  - Newborn neurons are generated in the adult hippocampus from a pool of self
      renewing stem cells located in the subgranular zone (SGZ) of the dentate gyrus.
      Their activation, proliferation, and maturation depend on a host of environmental
      and cellular factors but, until recently, the contribution of local neuronal
      circuitry to this process was relatively unknown. In their recent publication,
      Song and colleagues have uncovered a novel circuit-based mechanism by which
      release of the neurotransmitter, gamma-aminobutyric acid (GABA), from parvalbumin
      expressing (PV) interneurons, can hold radial glia-like (RGL) stem cells of the
      adult SGZ in a quiescent state. This tonic GABAergic signal, dependent upon the
      activation of gamma(2)  subunit-containing GABA(A)  receptors of RGL stem cells,
      can thus prevent their proliferation and subsequent maturation or return them to
      quiescence if previously activated. PV interneurons are thus capable of
      suppressing neurogenesis during periods of high network activity and facilitating
      neurogenesis when network activity is low.

PMID- 23165997
TI  - Promises and problems for the new paradigm for risk assessment and an alternative
      approach involving predictive systems models.
AB  - The need for cost-effective risk assessment of chemicals is leading to the
      development of a reductionist paradigm that tries to assess impacts on humans and
      ecosystems from molecular changes. However, the biggest challenge for this
      paradigm comes from the emergence of properties that arise out of the
      interactions of the parts that are not included and yet which are key for
      assessing likely impacts. Although identifying key events and adverse outcome
      pathways can shed light on the involvement of important metabolic processes in
      toxicity, this does not mean that particular molecular initiating events are
      likely to be robust or accurate predictors of impacts that matter. There are even
      greater challenges for the new paradigm applied to ecological systems than to
      human health because of the need to link across more levels of biological
      organization. The present study argues for a predictive systems approach that
      makes the linkages through systems models in a mechanistic way that allows for
      emergence and that also has the potential for reducing the costs and use of
      animals in ecological risk assessments.

PMID- 23165998
TI  - Determining the impacts of contaminants of emerging concern in marine ecosystems.

PMID- 23165999
TI  - Linear no threshold (LNT)--the new homeopathy.

PMID- 23166000
TI  - Review of vascularised bone tissue-engineering strategies with a focus on co
      culture systems.
AB  - Poor angiogenesis within tissue-engineered grafts has been identified as a main
      challenge limiting the clinical introduction of bone tissue-engineering (BTE)
      approaches for the repair of large bone defects. Thick BTE grafts often exhibit
      poor cellular viability particularly at the core, leading to graft failure and
      lack of integration with host tissues. Various BTE approaches have been explored
      for improving vascularisation in tissue-engineered constructs and are briefly
      discussed in this review. Recent investigations relating to co-culture systems of
      endothelial and osteoblast-like cells have shown evidence of BTE efficacy in
      increasing vascularization in thick constructs. This review provides an overview
      of key concepts related to bone formation and then focuses on the current state
      of engineered vascularized co-culture systems using bone repair as a model. It
      will also address key questions regarding the generation of clinically relevant
      vascularized bone constructs as well as potential directions and considerations
      for research with the objective of pursuing engineered co-culture systems in
      other disciplines of vascularized regenerative medicine. The final objective is
      to generate serious and functional long-lasting vessels for sustainable
      angiogenesis that will enable enhanced cellular survival within thick voluminous
      bone grafts, thereby aiding in bone formation and remodelling in the long term.
      However, more evidence about the quality of blood vessels formed and its
      associated functional improvement in bone formation as well as a mechanistic
      understanding of their interactions are necessary for designing better
      therapeutic strategies for translation to clinical settings.

PMID- 23166001
TI  - PANK2 and C19orf12 mutations are common causes of neurodegeneration with brain
      iron accumulation.
AB  - BACKGROUND: Neurodegeneration with brain iron accumulation (NBIA) constitutes a
      group of neurodegenerative disorders with pronounced iron deposition in the basal
      ganglia. PANK2 mutations are the most common cause of these disorders. C19orf12
      was recently reported as another causative gene. We present phenotypic data and
      results of screening of PANK2 and C19orf12 in 11 unrelated Iranian NBIA patients.
      METHODS: Phenotypic data were obtained by neurologic examination, magnetic
      resonance imaging, and interviews. Mutation screening of PANK2 and C19orf12 was
      performed by sequencing. RESULTS: PANK2 and C19orf12 mutations were found in 7
      and 4 patients, respectively. Phenotypic comparisons suggest that C19orf12
      mutations as compared with PANK2 mutations result in a milder disease course.
      CONCLUSIONS: Mutations in both PANK2 and C19orf12 contributed significantly to
      NBIA in the Iranian patients. To the best of our knowledge, this is the first
      genetic analysis reported on a cohort of NBIA patients from the Middle East.

PMID- 23166002
TI  - Impact of targeted neoadjuvant therapies in the treatment of solid organ tumours.
AB  - BACKGROUND: The advent of affordable technologies to perform detailed molecular
      profiling of tumours has transformed understanding of the specific genetic events
      that promote carcinogenesis and which may be exploited therapeutically. The
      application of targeted therapeutics has led to improved outcomes in advanced
      disease and this approach is beginning to become established in the management of
      potentially curable disease for surgical patients. METHODS: This review article
      focuses on recent developments in the management of operable cancers of the
      gastrointestinal (GI) tract, specifically discussing the currently available data
      that evaluate the incorporation of targeted therapies in this setting. RESULTS: A
      variety of targeted molecules are now available as treatment options in the
      management of GI cancers. Most are aimed at growth inhibition by acting on cell
      surface targets or intracellular pathways. Treatment paradigms are gradually
      shifting towards more prevalent use of systemic treatment prior to surgical
      intervention for operable disease with the aim of tumour downsizing and improved
      rates of long-term cure. CONCLUSION: A large number of ongoing clinical trials
      are evaluating novel targeted agents as neoadjuvant therapy in operable GI
      tumours. Therefore, further progress in the management of early-stage disease
      will undoubtedly be made over the next few years as these trials continue to
      report potentially practice-changing results.

PMID- 23166005
TI  - Discrimination of pseudo-meta and pseudo-para diamino
      octafluoro[2.2]paracyclophanes by (1)H, (19)F, and (13)C NMR.
AB  - Pseudo-meta and pseudo-para diamino-octafluoro[2.2]paracyclophanes are
      challenging to separate either by chromatography or recrystallization, but
      through the use of a mixture of the two isomers, the (1)H, (19)F, and (13)C NMR
      spectra of these compounds have been fully and unambiguously assigned using (1)H
      COSY, (1)H-(19)F HOESY, (1)H-(13)C HSQC, (1)H-(13)C HMBC, and (19)F-(13)C HSQC
      techniques. This permits the easy identification of either of the individual
      isomers. In addition, the (13)C spectrum of the pseudo-ortho analogue is reported
      and assigned for the first time. The gem shift effect in this series of bridge
      fluorinated paracyclophanes serves to deshield (1)H resonances and shield (13)C.

PMID- 23166003
TI  - Increased glutamate concentration in the auditory cortex of persons with autism
      and first-degree relatives: a (1)H-MRS study.
AB  - Increased glutamate levels have been reported in the hippocampal and frontal
      regions of persons with autism using proton magnetic resonance spectroscopy ((1)H
      MRS). Although autism spectrum disorders (ASDs) are highly heritable, MRS studies
      have not included relatives of persons with ASD. We therefore conducted a study
      to determine if glutamate levels are elevated in people with autism and parents
      of children with autism. Single-voxel, point-resolved spectroscopy data were
      acquired at 3T for left and right hemisphere auditory cortical voxels in 13
      adults with autism, 15 parents of children with autism, and 15 adult control
      subjects. The primary measure was glutamate + glutamine (Glx). Additional
      measures included n-acetyl-aspartate (NAA), choline (Cho), myoinositol (mI), and
      creatine (Cr). The autism group had significantly higher Glx, NAA, and Cr
      concentrations than the control subjects. Parents did not differ from control
      subjects on any measures. No significant differences in Cho or mI levels were
      seen among groups. No reliable correlations between autism symptom measures, and
      MRS variables were seen after Bonferroni correction for multiple comparisons. The
      elevation in Glx in autism is consistent with prior MRS data in the hippocampus
      and frontal lobe and may suggest increased cortical excitability. Increased NAA
      and Cr may indicate brain metabolism disturbances in autism. In the current
      study, we found no reliable evidence of a familial effect for any spectroscopy
      measure. This may indicate that these metabolites have no heritable component in
      autism, the presence of a compensatory factor in parents, or sample-specific
      limitations such as the participation of singleton families.

PMID- 23166006
TI  - Bright and stable alloy core/multishell quantum dots.
AB  - Color conversion: a quantum dot (QD) structure consisting of an alloy core
      (CdSe//ZnS) and multishells (CdSZnS) was prepared. The photoluminescence of the
      QDs could be tuned especially in the green-light region by controlling the
      thickness of the inner CdS shell. The alloy core/multishell (AC/MS) QDs showed a
      quantum efficiency of 100 % and a narrow spectrum width.

PMID- 23166007
TI  - OMIP-015: human regulatory and activated T-cells without intracellular staining.

PMID- 23166008
TI  - New routes to Cu(I)/Cu nanocatalysts for the multicomponent click synthesis of
      1,2,3-triazoles.
AB  - An array of copper and copper-zinc based nanoparticles (NPs) have been fabricated
      employing a variety of polymeric capping agents. Analysis by TEM, XRPD and XPS
      suggests that by manipulating reagent, reductant and solvent conditions it is
      possible to achieve materials that are mono-/narrow disperse with mean particle
      sizes in the <=10 nm regime. Oxidative stability in air is achieved for
      monometallic NPs using poly(methyl methacrylate) (PMMA) anti-agglomerant in
      conjunction with a variety of reducing conditions. In contrast, those
      encapsulated by either poly(1-vinylpyrrolidin-2-one) (PVP) or poly(4
      vinylpyridine) (PVPy) rapidly show Cu(2)O formation, with all data suggesting
      progressive oxidation from Cu to Cu@Cu(2)O core-shell structure and finally
      Cu(2)O. Bimetallic copper-zinc systems, reveal metal segregation and the
      formation of Cu(2)O and ZnO. Catalysts have been screened in the synthesis of
      1,2,3-triazoles through multicomponent azide-alkyne 1,3-dipolar cycloaddition.
      Whereas PMMA- and PVPy-coating results in reduced catalytic activity, those
      protected by PVP are highly active, with quantitative triazole syntheses achieved
      at room temperature and with catalyst loadings of 0.03 mol% metal for Cu and CuZn
      systems prepared using NaH(2)PO(2), N(2)H(4) or NaBH(4) reductants.

PMID- 23166009
TI  - Role of intestinal microflora in xenobiotic-induced toxicity.
AB  - In addition to its role in digestion of food in the gastrointestinal tract, the
      intestinal microflora is also capable of biotransforming numerous drugs.
      Likewise, the intestinal microflora may significantly modulate xenobiotic-induced
      toxicity by either activating or inactivating xenobiotics via metabolism. To
      date, most investigations of xenobiotic metabolism have focused not only on
      metabolism in host tissues, but the modulation of the pharmacological activity of
      drugs by the intestinal microflora. Despite its importance, the presumed role of
      intestinal microflora metabolism in xenobiotic-induced toxicity has been
      understudied. Therefore, it is appropriate to briefly review our current
      situation, and state which research in xenobiotic metabolism by intestinal
      microflora, particularly in the field of toxicology, is needed.

PMID- 23166011
TI  - Neurosyphilis orofacial dyskinesia: the candy sign.

PMID- 23166010
TI  - Phelan-McDermid syndrome: clinical report of a 70-year-old woman.
AB  - Phelan-McDermid or 22q13.3 deletion syndrome is characterized by global
      intellectual disability, childhood hypotonia, severely delayed or absent speech,
      features of autism spectrum disorder, without any major dysmorphisms or somatic
      anomalies. It is typically diagnosed before adolescence and data about adult
      patients are virtually absent. The expression of its phenotypical characteristics
      appears to be linearly related to the deletion size. Here, an intellectually
      disabled geriatric female patient is described with a long history of challenging
      behaviors in whom Phelan-McDermid syndrome was demonstrated. Detailed analysis of
      the patient's history and functioning resulted in a psychiatric diagnosis of
      atypical bipolar disorder and her behavior significantly improved upon
      maintenance treatment with a mood stabilizing agent. The present article confirms
      recent findings that atypical bipolar disorder may be part of the
      psychopathological phenotype of Phelan-McDermid syndrome, reason why careful
      etiological search is warranted, also in the geriatric population.

PMID- 23166012
TI  - Toxicity evaluation of two typical surfactants to Dunaliella bardawil, an
      environmentally tolerant alga.
AB  - Sodium dodecyl benzene sulfonate (SDBS) and cetyl trimethyl ammonium chloride
      (CTAC) are two kinds of surfactants widely applied in various industries. The
      tremendous direct discharge of these surfactants into natural waters has posed a
      significant threat to ecosystems. Dunaliella bardawil was employed in the present
      research to test the toxic effects of SDBS, CTAC, and their mixture on cell
      growth, cellular morphology, beta-carotene accumulation, and enzymatic activities
      of superoxide dismutase (SOD) and catalase (CAT). The results showed that SDBS at
      200, 550, 900, 1,350, 1,800, and 2,400 mg/L and CTAC at 0.4, 0.7, 1.0, 1.3, 2.8,
      and 3.5 mg/L inhibited algal growth and beta-carotene accumulation, both of which
      declined and then increased. In particular, CTAC (median inhibitory concentration
      at 10 days [IC50](10 d)  = 2.8 +/- 1.49 mg/L) was more hazardous than SDBS
      (IC50(10 d)  = 2,044 +/- 637.3 mg/L). The additive index (AI) calculated from
      carotene content data was (-4.10, -1.67) < 0, indicating an antagonistic effect
      between SDBS and CTAC. Algae cultivated at level 6 of the binary system showed
      hormesis due to the mitigated toxicity; SDBS at 2,400 mg/L, CTAC at 3.5 mg/L, and
      combined surfactants at level 6 exerted lethal effects on D. bardawil. Both SOD
      and CAT activities showed similar associations with varied concentrations of
      surfactants: SOD was significantly promoted by 550 to 1,800 mg/L SDBS, 0.7 to 1.3
      mg/L CTAC, and mixtures at levels 2 to 4; CAT was clearly promoted by 900 mg/L
      SDBS, 0.4 to 1.3 mg/L CTAC, and mixtures at levels 2 to 4.

PMID- 23166013
TI  - Association between iron content and gray matter missegmentation with voxel-based
      morphometry in basal ganglia.
AB  - PURPOSE: To show an association between T2-weighted signal intensity (T2-SI)
      variation and missegmentation in the putamen of healthy adults, using 3.0-tesla
      magnetic resonance scanner and voxel-based morphomery (VBM). MATERIALS AND
      METHODS: Contiguous sagittal T1-weighted images and axial T2-weighted images of
      the brain were obtained from 1380 healthy participants using a 3.0 Tesla (T) MR
      scanner. After image preprocessing with Statistical Parametric Mapping 5, the
      association between T2-SI ratio (= A/B, where A is the mean of the T2-SI in the
      putamen, and B is that in the thalamus) variation and gray matter missegmentation
      was assessed using VBM. RESULTS: A significant positive correlation was revealed
      between T2-SI ratio and bilateral putamen volume on the gray matter images. In
      addition, we found a significant negative correlation between T2-SI ratio and
      bilateral putamen volume on the white matter images. We consider that these
      results show the influence of missegmentation. CONCLUSION: To the best of our
      knowledge, this is the first VBM study to demonstrate an association between T2
      SI variation and gray matter missegmentation. These results indicate the
      possibility that VBM may be more affected by individual differences in iron
      content levels than by individual differences in tissue volumes if detected
      regions with VBM contained substantial iron deposition.

PMID- 23166014
TI  - Whole-cell vaccine coated with recombinant calreticulin enhances activation of
      dendritic cells and induces tumour-specific immune responses.
AB  - It has been reported that calreticulin (CRT) plays an important role in mediating
      immunogenic tumour cell death. In the process of tumour cell apoptosis induced by
      specific stimuli, CRT is quickly transferred from the endoplasmic reticulum to
      the cell membrane. As a specific ligand, CRT on the surface of apoptotic tumour
      cells could mediate the recognition and clearance of apoptotic tumour cells by
      professional and non-professional phagocytes. In our previous studies, we used
      B16-F1 mouse melanoma cells coated with mCRT-vGPCR (a recombinant fusion protein
      of mouse CRT and virus G-protein-coupled receptor) as a whole-cell tumour vaccine
      to immunise experimental animals and found that this whole-cell vaccine could
      strongly inhibit the growth of homologous tumours. In this study, we further
      evaluated immune responses induced by this mCRT-vGPCR-coated whole-cell vaccine
      both in vivo and in vitro. An in vitro phagocytosis assay showed that the mCRT
      vGPCR on the cell surface greatly enhanced the engulfment of B16-F1 cells by
      dendritic cells (DCs). The specific antitumour immune response was observed when
      the mCRT-vGPCR-coated B16-F1 cells were used as a whole-cell tumour vaccine to
      immune mice, which included significantly enhanced cytotoxic T lymphocyte (CTL)
      activities and increased the number of IFN-gamma-producing T cells. These results
      indicate that the mCRT-vGPCR-coated whole-cell vaccine can induce specific
      antitumour immunity though the activation of DCs. These results may provide an
      experimental basis for the development of new tumour vaccines.

PMID- 23166015
TI  - Liquid chromatography tandem mass spectrometry method for the simultaneous
      stereoselective determination of venlafaxine and its major metabolite, O
      desmethylvenlafaxine, in human plasma.
AB  - A sensitive, accurate and highly stereoselective assay for the simultaneous
      determination of venlafaxine (VEN) and its equipotent metabolite, O-desmethyl
      venlafaxine (ODV), in human plasma was developed and validated. Analytes were
      simultaneously extracted from plasma using solid-phase extraction and detected by
      tandem mass spectrometry in positive ion mode with a turbo ion spray interface.
      Deuterium-labeled VEN and ODV were used as internal standards. Chromatographic
      separation was performed on a Chiral AGP column, using a time programmed gradient
      flow with a total run time of 16 min. The method has a lower limit of
      quantitation of 0.60 ng/mL. The assay was linear over a range 0.60-300.00 ng/mL
      for both the enantiomers of VEN and ODV, respectively, with coefficient of
      correlation > 0.99. The extraction recoveries were >77.0% on an average for all
      the four analytes. The analytes were found stable in plasma through three freeze
      (-15  degrees C) and thaw cycles and under storage at room temperature for 8 h,
      and also in mobile phase at 10  degrees C for 54 h. The method has shown good
      reproducibility, with intra- and inter-day variation coefficients < 9%, for all
      the analytes, and has proved to be very reliable for analysis of VEN and its
      metabolite in clinical study samples.

PMID- 23166016
TI  - 2-(trimethylammonium)ethyl (R)-3-methoxy-3-oxo-2-stearamidopropyl phosphate
      promotes megakaryocytic differentiation of myeloid leukaemia cells and primary
      human CD34+ haematopoietic stem cells.
AB  - In this study we showed that 2-(trimethylammonium)ethyl (R)-3-methoxy-3-oxo-2
      stearamidopropyl phosphate [(R)-TEMOSPho], a derivative of an organic chemical
      identified from a natural product library, promotes highly efficient
      differentiation of megakaryocytes. Specifically, (R)-TEMOSPho induces cell cycle
      arrest, cell size increase and polyploidization from K562 and HEL cells, which
      are used extensively to model megakaryocytic differentiation. In addition,
      megakaryocyte-specific cell surface markers showed a dramatic increase in
      expression in response to (R)-TEMOSPho treatment. Importantly, we demonstrated
      that such megakaryocytic differentiation can also be induced from primary human
      CD34(+) haematopoietic stem cells. Activation of the PI3K-AKT pathway and, to a
      lesser extent, the MEK-ERK pathway appears to be required for this process, as
      blocking with specific inhibitors interferes with the differentiation of K562
      cells. A subset of (R)-TEMOSPho-treated K562 cells undergoes spontaneous
      apoptosis and produces platelets that are apparently functional, as they bind to
      fibrinogen, express P-selectin and aggregate in response to SFLLRN and AYPGFK,
      the activating peptides for the PAR1 and PAR4 receptors, respectively. Taken
      together, these results indicate that (R)-TEMOSPho will be useful for dissecting
      the molecular mechanisms of megakaryocytic differentiation, and that this class
      of compounds represents potential therapeutic reagents for thrombocytopenia.

PMID- 23166017
TI  - Object-directed imitation in children with high-functioning autism: testing the
      social motivation hypothesis.
AB  - Children with autism show clear deficits in copying others' bodily oriented
      actions whereas their capacity for replicating others' object-directed actions
      appears relatively spared. One explanation is that unlike bodily oriented
      actions, object-directed actions have tangible, functional outcomes and hence
      rely far less on social motivations for their production. To investigate this, we
      compared the performance of a group of children with high-functioning autism
      (HFA) and a group of typically developing (TD) children on two distinct object
      directed tasks that are considered highly social: overimitation and synchronic
      imitation. Our findings were surprising. The HFA children copied all of a
      modeling adult's actions, including those that had no function or purpose (i.e.
      they overimitated), and they entered into extended bouts repeating an arbitrary
      action along with the adult who had a similar object to play with (i.e. they
      engaged in synchronic imitation). Moreover, they did so at rates
      indistinguishable from the TD children. This work demonstrates that the capacity
      and propensity for overimitation and synchronic imitation are intact in children
      with HFA, and questions whether socially based imitation should be considered an
      autism-specific deficit.

PMID- 23166018
TI  - Generating extracellular amyloid aggregates using E. coli cells.
AB  - Diverse proteins are known to be capable of forming amyloid aggregates, self
      seeding fibrillar assemblies that may be biologically functional or pathological.
      Well-known examples include neurodegenerative disease-associated proteins that
      misfold as amyloid, fungal prion proteins that can transition to a self
      propagating amyloid form and certain bacterial proteins that fold as amyloid at
      the cell surface and promote biofilm formation. To further explore the diversity
      of amyloidogenic proteins, generally applicable methods for identifying them are
      critical. Here we describe a cell-based method for generating amyloid aggregates
      that relies on the natural ability of Escherichia coli cells to elaborate amyloid
      fibrils at the cell surface. We use several different yeast prion proteins and
      the human huntingtin protein to show that protein secretion via this specialized
      export pathway promotes acquisition of the amyloid fold specifically for proteins
      that have an inherent amyloid-forming propensity. Furthermore, our findings
      establish the potential of this E. coli-based system to facilitate the
      implementation of high-throughput screens for identifying amyloidogenic proteins
      and modulators of amyloid aggregation.

PMID- 23166020
TI  - Decrease in RNA folding cooperativity by deliberate population of intermediates
      in RNA G-quadruplexes.
AB  - Keeping a broad (RNA) perspective: conventional biochemical detection systems
      only have a 100-fold linear response range. The range of potassium concentrations
      detected by an RNA G-quadruplex sequence can be broadened by intentionally
      populating multiple intermediate folding states. The folding of the RNA G
      quadruplexes was monitored by both circular dichroism and intrinsic fluorescence
      spectroscopy.

PMID- 23166019
TI  - Enhancer-associated H3K4 monomethylation by Trithorax-related, the Drosophila
      homolog of mammalian Mll3/Mll4.
AB  - Monomethylation of histone H3 on Lys 4 (H3K4me1) and acetylation of histone H3 on
      Lys 27 (H3K27ac) are histone modifications that are highly enriched over the body
      of actively transcribed genes and on enhancers. Although in yeast all H3K4
      methylation patterns, including H3K4me1, are implemented by Set1/COMPASS (complex
      of proteins associated with Set1), there are three classes of COMPASS-like
      complexes in Drosophila that could carry out H3K4me1 on enhancers: dSet1,
      Trithorax, and Trithorax-related (Trr). Here, we report that Trr, the Drosophila
      homolog of the mammalian Mll3/4 COMPASS-like complexes, can function as a major
      H3K4 monomethyltransferase on enhancers in vivo. Loss of Trr results in a global
      decrease of H3K4me1 and H3K27ac levels in various tissues. Assays with the cut
      wing margin enhancer implied a functional role for Trr in enhancer-mediated
      processes. A genome-wide analysis demonstrated that Trr is required to maintain
      the H3K4me1 and H3K27ac chromatin signature that resembles the histone
      modification patterns described for enhancers. Furthermore, studies in the
      mammalian system suggested a role for the Trr homolog Mll3 in similar processes.
      Since Trr and mammalian Mll3/4 complexes are distinguished by bearing a unique
      subunit, the H3K27 demethylase UTX, we propose a model in which the H3K4
      monomethyltransferases Trr/Mll3/Mll4 and the H3K27 demethylase UTX cooperate to
      regulate the transition from inactive/poised to active enhancers.

PMID- 23166021
TI  - Soliton-like thermophoresis of graphene wrinkles.
AB  - We studied the thermophoretic motion of wrinkles formed in substrate-supported
      graphene sheets by nonequilibrium molecular dynamics simulations. We found that a
      single wrinkle moves along applied temperature gradient with a constant
      acceleration that is linearly proportional to temperature deviation between the
      heating and cooling sides of the graphene sheet. Like a solitary wave, the atoms
      of the single wrinkle drift upwards and downwards, which prompts the wrinkle to
      move forwards. The driving force for such thermophoretic movement can be mainly
      attributed to a lower free energy of the wrinkle back root when it is transformed
      from the front root. We establish a motion equation to describe the soliton-like
      thermophoresis of a single graphene wrinkle based on the Korteweg-de Vries
      equation. Similar motions are also observed for wrinkles formed in a Cu-supported
      graphene sheet. These findings provide an energy conversion mechanism by using
      graphene wrinkle thermophoresis.

PMID- 23166022
TI  - Students' understanding of external representations of the potassium ion channel
      protein, part I: affordances and limitations of ribbon diagrams, vines, and
      hydrophobic/polar representations.
AB  - Research on external representations in biochemistry has uncovered student
      difficulties in comprehending and interpreting external representations. This
      project focuses on students' understanding of three external representations of
      the potassium ion channel protein. This is part I of a two-part study, which
      focuses on the affordances and limitations of representations of the potassium
      ion channel according to students across the chemistry and biochemistry
      curriculum. Analysis showed that if the students do not possess the required
      prior knowledge then they are stymied in their interpretations of the
      representations. Students were able to easily interpret the familiar ribbon
      diagram representation; however, they found the vines and hydrophobic/polar
      representations to be less informative. Suggestions for instruction are to probe
      student understanding and to help students activate prior knowledge to build a
      more connected set of concepts pertaining to protein structure.

PMID- 23166023
TI  - Students' understanding of external representations of the potassium ion channel
      protein part II: structure-function relationships and fragmented knowledge.
AB  - Research that has focused on external representations in biochemistry has
      uncovered student difficulties in comprehending and interpreting external
      representations. This study focuses on students' understanding of three external
      representations (ribbon diagram, wireframe, and hydrophobic/hydrophilic) of the
      potassium ion channel protein. Analysis of the interview data demonstrates that
      students were able to use the ribbon structures and polarity of the cell membrane
      to help support claims about the protein's orientation and interactions within
      the cell membrane. Students expressed fragmented understandings of the
      interactions between the potassium ion and the aqueous solution outside/inside of
      the cell membrane. Suggestions for instruction are to probe student understanding
      to help students activate prior knowledge and to help them build a more connected
      set of concepts pertaining to protein structure and function.

PMID- 23166024
TI  - A laboratory course for teaching laboratory techniques, experimental design,
      statistical analysis, and peer review process to undergraduate science students.
AB  - This article describes a 13-week laboratory course called Human Toxicology taught
      at the University of Otago, New Zealand. This course used a guided inquiry based
      laboratory coupled with formative assessment and collaborative learning to
      develop in undergraduate students the skills of problem solving/critical
      thinking, data interpretation and written discussion of results. The laboratory
      practices were a guided inquiry based around retinol's ability to potentiate
      acetaminophen-mediated hepatotoxicity. To induce critical thinking, students were
      given a choice as to which assay they could use to determine how retinol affected
      acetaminophen hepatotoxicity. Short summaries were handed in following each assay
      and formed the bases of the formative assessment. To complete the feedback loop,
      a summative assessment that consisted of all the graphs and concepts from the
      short summaries were combined into a manuscript. To give the students exposure to
      science communication, the manuscript had to be written in accordance to the
      submission guidelines for Toxicological Sciences. Evaluation of this course was
      determined by a student questionnaire using a Likert scale and students'
      responses were very favorable. While the subject matter was toxicological
      centric, the content could be easily modified to suit another subject matter in
      biochemistry and molecular biology.

PMID- 23166025
TI  - Protein analysis by dynamic light scattering: methods and techniques for
      students.
AB  - Dynamic light scattering (DLS) analyses are routinely used in biology
      laboratories to detect aggregates in macromolecular solutions, to determine the
      size of proteins, nucleic acids, and complexes or to monitor the binding of
      ligands. This article is written for graduate and undergraduate students with
      access to DLS and for faculty members who wish to incorporate DLS into a lab
      activity, a practical course or research. It reviews the basic concepts of light
      scattering measurements and addresses four critical aspects of the analysis and
      interpretation of DLS results. To ensure reproducible quantitative data,
      attention should be paid to controlling the preparation and handling of proteins
      or assemblies because variations in the state of aggregation, induced by minor
      changes in experimental condition or technique, might compromise DLS results and
      affect protein activity. Variables like temperature, solvent viscosity, and inter
      particle interactions may also influence particle size determination. Every point
      is illustrated by case studies, including a commercially available albumin, a
      small RNA virus isolated from plants, as well as four soluble proteins and a
      ribonucleoprotein assembly purified and characterized by students in the frame of
      their master degree.

PMID- 23166026
TI  - Using electrophoretic mobility shift assays to measure equilibrium dissociation
      constants: GAL4-p53 binding DNA as a model system.
AB  - An undergraduate biochemistry laboratory experiment is described that will teach
      students the practical and theoretical considerations for measuring the
      equilibrium dissociation constant (K(D) ) for a protein/DNA interaction using
      electrophoretic mobility shift assays (EMSAs). An EMSA monitors the migration of
      DNA through a native gel; the DNA migrates more slowly when bound to a protein.
      To determine a K(D)  the amount of unbound and protein-bound DNA in the gel is
      measured as the protein concentration increases. By performing this experiment,
      students will be introduced to making affinity measurements and gain experience
      in performing quantitative EMSAs. The experiment describes measuring the K(D) 
      for the interaction between the chimeric protein GAL4-p53 and its DNA recognition
      site; however, the techniques are adaptable to other DNA binding proteins. In
      addition, the basic experiment described can be easily expanded to include
      additional inquiry-driven experimentation. (c) 2012 by The International Union of
      Biochemistry and Molecular Biology.

PMID- 23166027
TI  - Using a scholarly approach to improve teaching and learning in biochemistry
      higher education.

PMID- 23166028
TI  - Problem-solving test: nucleocytoplasmic shuttling of pre-mRNA binding proteins.
AB  - Terms to be familiar with before you start to solve the test: transcription, pre
      mRNA, RNA processing, RNA transport, RNA polymerase II, direct and indirect
      immunofluorescence staining, cell fractionation by centrifugation, oligo(dT)
      cellulose chromatography, washing and elution of the column, ribonuclease, SDS
      polyacrylamide gel electrophoresis, Western-blotting, pre-ribosomal particles,
      nuclear envelope, heterokaryon, phase contrast microscopy, polyadenylated RNA.

PMID- 23166029
TI  - Simulation of two dimensional electrophoresis and tandem mass spectrometry for
      teaching proteomics.
AB  - In proteomics, complex mixtures of proteins are separated (usually by
      chromatography or electrophoresis) and identified by mass spectrometry. We have
      created 2DE Tandem MS, a computer program designed for use in the biochemistry,
      proteomics, or bioinformatics classroom. It contains two simulations-2D
      electrophoresis and tandem mass spectrometry. The two simulations are integrated
      together and are designed to teach the concept of proteome analysis of
      prokaryotic and eukaryotic organisms. 2DE-Tandem MS can be used as a freestanding
      simulation, or in conjunction with a wet lab, to introduce proteomics in the
      undergraduate classroom. 2DE Tandem MS is a free program available on Sourceforge
      at https://sourceforge.net/projects/jbf/. It was developed using Java Swing and
      functions in Mac OSX, Windows, and Linux, ensuring that every student sees a
      consistent and informative graphical user interface no matter the computer
      platform they choose. Java must be installed on the host computer to run 2DE
      Tandem MS. Example classroom exercises are provided in the Supporting
      Information.

PMID- 23166030
TI  - Proteopedia: 3D visualization and annotation of transcription factor-DNA readout
      modes.
AB  - 3D visualization assists in identifying diverse mechanisms of protein-DNA
      recognition that can be observed for transcription factors and other DNA binding
      proteins. We used Proteopedia to illustrate transcription factor-DNA readout
      modes with a focus on DNA shape, which can be a function of either nucleotide
      sequence (Hox proteins) or base pairing geometry (p53). (c) 2012 by The
      International Union of Biochemistry and Molecular Biology.

PMID- 23166034
TI  - DNA microarray analysis identified molecular pathways mediating the effects of
      supplementation of branched-chain amino acids on CCl4-induced cirrhosis in rats.
AB  - SCOPE: This study addresses the effects of branched-chain amino acids (BCAA) on
      global gene expression in liver and skeletal muscle and the molecular mechanisms
      underlying the improvement in liver cirrhosis using DNA microarray analysis
      combined with RNase protection assay. METHODS AND RESULTS: Male Wistar rats
      administered carbon tetrachloride (CCl(4) ) repeatedly for 19 weeks as a
      decompensated cirrhosis model were thereafter given BCAA-enriched diet (AL) or
      normal diet (LC) for 5 weeks. The control-diet rats without CCl(4) 
      administration were used as a normal control group. Gene expression in AL was
      reversed by twofold greater than in LC in the microarray were selected to
      elucidate the improvements in nutritional and metabolic disorders. Downregulation
      of fatty acid translocase (FAT)/Cd36, glutamine synthetase, and pyruvate
      dehydrogenase kinase isoenzyme 4 is believed to promote lower uptake of fatty
      acids, lower ammonia incorporation, and higher uptake of glucose, and thus to
      provide an energy source without using BCAA. Ultimately, the catabolism of BCAA
      and skeletal muscle protein would be slowed, maintaining BCAA concentrations in
      blood. CONCLUSION: We established, for the first time, the regulatory gene
      pathways of processes involved in hepatic fibrosis and energy metabolism
      (hypoalbuminemia, hyperammonemia, and carbohydrate catabolism, and their
      relationships) under BCAA supplementation.

PMID- 23166035
TI  - Improving alginate-poly-L-ornithine-alginate capsule biocompatibility through
      genipin crosslinking.
AB  - DIABECELL(r) capsules comprise an inner core of alginate (Alg) coated with a
      polycationic polymer, poly-L-ornithine (PLO), designed as a stabilizing agent for
      strengthening the capsule wall, which is masked by an outer layer of
      biocompatible Alg. These polymeric microcapsules have demonstrated excellent
      mechanical properties and a reduction in hypoglycemia after tranplantation in
      human clinical trials; however, degradation of the outer Alg layer leaves the
      underlying layers of PLO exposed, which ultimately leads to reduced
      biocompatibility in vivo. Here we aim to improve capsule biocompatibility and to
      increase the hydrophilic properties of the capsule surface through chemical
      crosslinking/modification of the PLO layer using genipin. Fluorescence microscopy
      established crosslinking was limited to the layers of PLO. In vitro experiments
      confirmed islet viability and insulin release within chemically modified capsules
      over the course of a month and in vivo investigations demonstrated improved
      biocompatibility when comparing standard Alg/PLO/Alg capsules with genipin
      modified capsules.

PMID- 23166036
TI  - Brothers with hypospadias, vertebral segmentation defects, and intellectual
      disability: new syndrome?
AB  - We report on two brothers (born to nonconsanguineous parents) with short stature,
      hypospadias, scoliosis, vertebral segmentation defects of "spondylocostal
      dysostosis" type, and intellectual disability. Results of cytogenetic and
      molecular genetic tests performed, including routine karyotype, MLPA (multiplex
      ligation-dependent probe amplification) for common microdeletions and
      subtelomeric copy number variants, microarray-CGH analysis, and sequencing of
      four Notch signaling pathway genes (DLL3, MESP2, LFNG, and HES7), were all
      normal. We present a comparison of the condition in the two boys with known
      syndromes and suggest that they may represent a hitherto unreported syndrome,
      most likely following autosomal recessive inheritance, though X-linked
      inheritance is not excluded.

PMID- 23166037
TI  - Safety of SSRIs during pregnancy: a controlled study.
AB  - OBJECTIVE: The objective of our study was to analyze the efficacy and the safety
      of SSRIs during pregnancy. METHODS: A group of 30 pregnant women affected by
      Major Depressive Disorder by SCID I interview (Diagnostic and Statistical Manual
      of Mental Disorders, Fourth Edition Text Revision criteria) and treated with
      selective serotonin reuptake inhibitor (SSRI) were included in the study. They
      were matched to a comparison group of 26 pregnant women. RESULTS: There were no
      statistically significant differences in any of the pregnancy outcomes of
      interest between the treated women and comparison group. There was no
      statistically significant association in newborns of women treated with an SSRI
      and the control group in the first and fifth minute Apgar score, and no newborns
      were admitted to neonatal Intensive Care Units. CONCLUSIONS: No definitive
      association between use of SSRIs during pregnancy and an increased risk of birth
      defects or other adverse outcomes could be found.

PMID- 23166038
TI  - Observation of two N2-isobutyrylguanine tautomers by NMR spectroscopy.
AB  - N(2)-isobutyrylguanine was prepared by treatment of guanine with isobutyryl
      chloride. Two tautomers, 1,7-dihydro-2-(isobutyroyl)amino-6H-purin-6-one and 1,9
      dihydro-2-(isobutyroyl)amino-6H-purin-6-one, were identified in almost 1:1 ratio
      in dichloromethane-dimethyl sulfoxide (1:1 v/v) by NMR spectroscopy. By using the
      selective-inversion experiments, enthalpy, entropy, and free energy for
      activation were determined. This work represents the first report of guanine
      tautomers observed directly by NMR spectroscopy.

PMID- 23166039
TI  - Stabilization of zeylenone in rat plasma by the presence of esterase inhibitors
      and its LC-MS/MS assay for pharmacokinetic study.
AB  - Six esterase inhibitors, namely EDTA.2Na(+), NaF, phenylmethanesulfonyl fluoride,
      dichlorvos, bis-nitrophenyl phosphate (BNPP) and thenoyltrifluoroacetone, and the
      mixture of NaF and BNPP, were evaluated for the stabilization of labile benzoate
      containing zeylenone in rat plasma. The mixture appeared to exhibit the most
      effectively stabilizing effect with the degraded content of zeylenone decreasing
      from >60% (in the absence of inhibitors) to <6%. Following the stabilization by
      the addition of NaF (5 mM) and BNPP (5 mM), the analytes in rat plasma were
      acidified by formic acid and extracted into ethyl acetate at 0 degrees C. After
      chromatographic separation, the detection of zeylenone was performed on a 3200 Q
      Trap with positive ion electrospray mode, monitoring the ion transition m/z 383.2
      -> 105.0. The method was validated over the range from 2.68 to 1340 ng/mL with
      inter- and intra-run precision for the quality control samples being less than
      6.8%. The assay accuracy was within 100 +/- 7.0%. The validated method was
      successfully applied to a pharmacokinetic study in rats after the intratracheal
      administration of zeylenone in free drug or polymeric micellar solutions. The
      results showed that the pulmonary absorption of zeylenone loaded in micelles was
      significantly retarded compared with that of free drug solutions.

PMID- 23166040
TI  - MRI of carotid atherosclerosis to identify TIA and stroke patients who are at
      risk of a recurrence.
AB  - PURPOSE: To evaluate the potential of carotid plaque MRI to predict transient
      ischemic attack (TIA) and stroke recurrence in previously symptomatic patients.
      MATERIALS AND METHODS: One hundred twenty-six TIA/stroke patients with
      ipsilateral 30-69% carotid stenosis underwent multisequence carotid plaque MRI.
      The presence of a lipid-rich necrotic core (LRNC), fibrous cap (FC) status, and
      intraplaque hemorrhage (IPH) were assessed. Patients were followed to determine
      the recurrence of ipsilateral TIA and/or stroke within 1 year after inclusion.
      RESULTS: Thirteen patients suffered from recurrent ipsilateral clinical ischemic
      events (10 TIAs and 3 strokes). Carotid stenosis grade was not associated with
      recurrent events (hazard ratio [HR] for 50-69% versus 30-49% stenosis = 1.198;
      95% confidence interval [CI], 0.383 to 3.749; P = 0.756). The presence of an LRNC
      (HR = 3.2001; 95% CI, 1.078 to 9.504; P = 0.036), a thin and/or ruptured FC (HR =
      5.756; 95% CI, 1.913 to 17.324; P = 0.002), and IPH (HR = 3.542; 95% CI, 1.058 to
      11.856; P = 0.040) were associated with recurrence. CONCLUSION: The presence of
      MRI-depicted LRNC, a thin and/or ruptured FC, and IPH are associated with the
      recurrence of clinical cerebrovascular ischemic events in TIA and stroke patients
      with carotid atherosclerosis.

PMID- 23166041
TI  - Efficacy of a dose-intensified CHOP (Double-CHOP) regimen for peripheral T-cell
      lymphomas.
AB  - Peripheral T-cell lymphomas (PTCLs) are a rare and heterogeneous group of non
      Hodgkin lymphomas, often resulting in poor prognoses. The CHOP chemotherapy
      regimen, which includes cyclophosphamide, doxorubicin, vincristine and
      prednisone, has been used previously to treat other types of lymphomas. Here, we
      examined the efficacy and safety of a dose-intensified CHOP regimen (Double
      CHOP), which was followed by autologous stem-cell transplantation (ASCT) or high
      dose methotrexate (HDMTX), in PTCL patients. Twenty-eight PTCL patients, who
      received 3 courses of Double-CHOP at our institution, were retrospectively
      studied from 1996 to 2012. Patients with anaplastic lymphoma kinase-positive
      anaplastic large-cell lymphoma (ALK+-ALCL) were excluded from this study. The
      median age of patients was 58 years (range: 17-69). They had low-intermediate
      (n=11), high-intermediate (n=10) or high (n=7) risk according to the
      International Prognostic Index (IPI). The overall complete remission (CR) rate
      following Double-CHOP treatment was 68%. Of the CR patients, 10 successfully
      tolerated a consolidated high-dose chemotherapy followed by ASCT and 7 received
      HDMTX. A single case of treatment-related mortality was recorded during the
      study. On a median 31-month follow-up, the estimated 3- or 5-year overall
      survival (OS) rates were 68 or 63%, respectively, while 3- or 5-year relapse-free
      survival (RFS) rates after CR were 60 or 43%, respectively. Although this study
      included elderly and excluded low-risk IPI and ALK+-ALCL patients, OS results
      were superiorly favourable, indicating the efficacy of this Double-CHOP regimen.
      However, an effective treatment strategy for refractory or relapsing patients
      needs to be validated and established.

PMID- 23166042
TI  - The postural autonomic regulation of pulpal blood flow.
AB  - Evidence suggests that postural changes in systemic blood pressure may
      significantly affect blood flow in the dental pulp. This in vivo study examined
      the responses of pulpal perfusion, systemic blood pressure, and heart rate to
      postural changes in humans. The experiments were done on 21 premolars in 16
      participants aged 20-31 yrs. Pulpal blood flow recordings were measured by means
      of a laser Doppler Flowmeter. A blood pressure monitor was used to record blood
      pressure and heart rate. All measurements were simultaneously recorded for 1 min,
      5 min after participants made postural changes. Changing from supine to standing
      caused a significant reduction in pulpal perfusion, while heart rate and
      diastolic blood pressure increased significantly. A significant non-linear
      relationship was found between percentage changes in pulpal perfusion and heart
      rate resulting from standing up. We speculate that when patients arise from the
      supine position, the shift in venous blood to the legs transiently (2-10 sec)
      lowers venous return and cardiac output, causing less inhibition of the vasomotor
      center, which, in turn, results in increased heart rate and blood pressure, but a
      decrease in pulpal blood flow. These results suggest that pulpal blood flow is
      affected by postural change, presumably via the autonomic nervous system.

PMID- 23166043
TI  - Shear mechanics of the TMJ disc: relationship to common clinical observations.
AB  - The temporomandibular joint (TMJ) is a complex hinge and gliding joint that
      induces significant shear loads onto the fibrocartilage TMJ disc during jaw
      motion. The purpose of this study was to assess regional variation in the disc's
      shear loading characteristics under physiologically relevant loads and to
      associate those mechanical findings with common clinical observations of disc
      fatigue and damage. Porcine TMJ discs were compressed between an axially
      translating bottom platen and a 2.5-cm-diameter indenter within a hydrated
      testing chamber. Discs were cyclically sheared at 0.5, 1, or 5 Hz to 1, 3, or 5%
      shear strain. Within the anterior and intermediate regions of the disc when
      sheared in the anteroposterior direction, both shear and compressive moduli
      experienced a significant decrease from instantaneous to steady state, while the
      posterior region's compressive modulus decreased approximately 5%, and no
      significant loss of shear modulus was noted. All regions retained their shear
      modulus within 0.5% of instantaneous values when shear was applied in the
      mediolateral direction. The results of the disc's regional shear mechanics
      suggest an observable and predictable link with the common clinical observation
      that the posterior region of the disc is most often the zone in which fatigue
      occurs, which may lead to disc damage and perforation.

PMID- 23166044
TI  - Inhibiting periapical lesions through AAV-RNAi silencing of cathepsin K.
AB  - Dental caries, one of the most prevalent infectious diseases worldwide, affects
      approximately 80% of children and the majority of adults. Dental caries may
      result in endodontic disease, leading to dental pulp necrosis, periapical
      inflammation and bone resorption, severe pain, and tooth loss. Periapical
      inflammation may also increase inflammation in other parts of the body. Although
      many studies have attempted to develop therapies for this disease, there is still
      an urgent need for effective treatments. In this study, we applied a novel gene
      therapeutic approach using recombinant adeno-associated virus (AAV)-mediated RNAi
      knockdown of Cathepsin K (Ctsk) gene expression, to target osteoclasts and
      periapical bone resorption in a mouse model. We found that AAV-sh-Cathepsin K
      (AAV-sh-Ctsk) impaired osteoclast function in vivo and furthermore reduced
      bacterial infection-stimulated bone resorption by 88%. Reduced periapical lesion
      size was accompanied by decreases in mononuclear leukocyte infiltration and
      inflammatory cytokine expression. Our study shows that AAV-RNAi silencing of
      Cathepsin K in periapical tissues can significantly reduce endodontic disease
      development, bone destruction, and inflammation in the periapical lesion. This is
      the first demonstration that AAV-mediated RNAi knockdown gene therapy may
      significantly reduce the severity of endodontic disease.

PMID- 23166045
TI  - Cell viability and angiogenic potential of a bioartificial adipose substitute.
AB  - An implantable scaffold pre-seeded with cells needs to remain viable and
      encourage rapid angiogenesis in order to replace injured tissues, especially for
      tissue defect repairs. We created a bioartificial adipose graft composed of an
      electrospun 3D nanofibrous scaffold and fat tissue excised from New Zealand white
      rabbits. Cell viability and angiogenesis potential of the bioartificial
      substitute were examined during four weeks of culture in Dulbecco's Modified
      Eagle Medium by immunohistochemical staining with LIVE/DEAD(r) cell kit and PECAM
      1 antibody, respectively. In addition, a Matrigel(r) assay was performed to
      examine the possibility of blood vessels sprouting from the bioartificial graft.
      Our results showed that cells within the graft were viable and vascular tubes
      were present at week 4, while cells in a fat tissue block were dead in vitro. In
      addition, capillaries were observed sprouting from the graft into the Matrigel,
      demonstrating its angiogenic potential. We expect that improved cell viability
      and angiogenesis in the bioartificial substitute, compared to intact autologous
      graft, could potentially contribute to its survival following implantation.

PMID- 23166046
TI  - External regulation of controlled polymerizations.
AB  - Polymer chemists, through advances in controlled polymerization techniques and
      reliable post-functionalization methods, now have the tools to create materials
      of almost infinite variety and architecture. Many relevant challenges in
      materials science, however, require not only functional polymers but also on
      demand access to the properties and performance they provide. The power of such
      temporal and spatial control of polymerization can be found in nature, where the
      production of proteins, nucleic acids, and polysaccharides helps regulate
      multicomponent systems and maintain homeostasis. Here we review existing
      strategies for temporal control of polymerizations through external stimuli
      including chemical reagents, applied voltage, light, and mechanical force. Recent
      work illustrates the considerable potential for this emerging field and provides
      a coherent vision and set of criteria for pursuing future strategies for
      regulating controlled polymerizations.

PMID- 23166047
TI  - Technical review of the da Vinci surgical telemanipulator.
AB  - BACKGROUND: The da Vinci robotic surgical telemanipulator has been utilized in
      several surgical specialties for varied procedures, and the users' experiences
      have been widely published. To date, no detailed system technical analyses have
      been performed. METHODS: A detailed review was performed of all publications and
      patents about the technical aspects of the da Vinci robotic system. RESULTS:
      Published technical literature on the da Vinci system highlight strengths and
      weaknesses of the robot design. While the system facilitates complex surgical
      operations and has a low malfunction rate, the lack of haptic (especially
      tactile) feedback and collisions between the robotic arms remain the major
      limitations of the system. Accurate, preplanned positioning of access ports is
      essential. CONCLUSION: Knowledge of the technical aspects of the da Vinci robot
      is important for optimal use. We confirmed the excellent system functionality and
      ease of use for surgeons without an engineering background. Research and
      development of the surgical robot has been predominant in the literature. Future
      trends address robot miniaturization and intelligent control design.

PMID- 23166048
TI  - Surface treatment, corrosion behavior, and apatite-forming ability of Ti-45Nb
      implant alloy.
AB  - The low modulus beta-type Ti-45Nb alloy is a promising new implant alloy due to
      its excellent mechanical biocompatibility and composition of non-toxic elements.
      The effect of surface treatments on the evolution of controlled topography and
      roughness was investigated by means of scanning electron microscopy and optical
      profilometry. Severe mechanical treatments, for example sand-blasting, or etching
      treatments in strongly oxidizing acidic solutions, like HF:HNO(3) (4:1) or
      H(2)SO(4):H(2)O(2) (1:1) piranha solution were found to be very effective. In
      particular, the latter generates a nanopatterned surface topography which is
      expected to be promising for the stimulation of bone tissue growth. Compared to
      Ti and Ti-6Al-4V, the beta-type Ti-45Nb alloy requires significantly longer
      etching durations due to the high chemical stability of Nb. Severe surface
      treatments alter the passive film properties, but do not deteriorate the
      outstanding corrosion resistance of the Ti-45Nb alloy in synthetic body fluid
      environments. The Ti-45Nb appears to have a lower apatite-formation ability
      compared to Ti. Etching with H(2)SO(4):H(2)O(2) (1:1) piranha solution inhibits
      apatite formation on Ti, but not on Ti-45Nb.

PMID- 23166049
TI  - Evaluation of cell function upon nanovector internalization.
AB  - In vitro toxicity assays based on the evaluation and retention of advanced and
      specific cellular functions are proposed to investigate mesoporous silicon
      nanovectors. This approach provides greater insight compared to simple cellular
      viability and toxicity assays. Electron microscopy images demonstrate
      internalized nanovectors altering the curvature of the nuclear envelope with
      minimal effect on viability or biological function.

PMID- 23166050
TI  - Intelligent, self-powered, drug delivery systems.
AB  - Self-propelled nano/micromotors and pumps are considered to be next generation
      drug delivery systems since the carriers can either propel themselves ("motor"
      based drug delivery) or be delivered ("pump"-based drug delivery) to the target
      in response to specific biomarkers. Recently, there has been significant
      advancement towards developing nano/microtransporters into proof-of-concept tools
      for biomedical applications. This review encompasses the progress made to date on
      the design of synthetic nano/micromotors and pumps with respect to transportation
      and delivery of cargo at specific locations. Looking ahead, it is possible to
      imagine a day when intelligent machines navigate through the human body and
      perform challenging tasks.

PMID- 23166051
TI  - Development and characterization of a vector set with regulated promoters for
      systematic metabolic engineering in Saccharomyces cerevisiae.
AB  - A set of vectors was constructed that enable combined and systematic testing of
      metabolic pathway genes in Saccharomyces cerevisiae. The vectors are available as
      CEN/ARS and 2 u-based plasmids with a choice of three inducible promoters,
      P(GAL1) , P(CUP1) and P(ADH2) . These features offer control over the initiation
      and level of gene expression. In addition, the vectors can be used as templates
      to generate PCR fragments for targeted chromosomal integration of gene expression
      cassettes. Selection markers are flanked by loxP elements to allow efficient CreA
      mediated marker removal and recycling after genomic integration. For each
      promoter, expression of a bacterial lacZ reporter gene was characterized from
      plasmid-based and integrated chromosomal cassettes, and compared to that of the
      glycolytic P(PGK1) promoter. Plasmid stabilities were also determined. The
      promoters showed distinct activity profiles useful for modulating expression of
      metabolic pathway genes. This series of plasmids with inducible promoters extends
      our previous vector set carrying the constitutive promoters P(PGK1) , P(TEF1) and
      P(HXT7-391) .

PMID- 23166052
TI  - Executive functioning in individuals with schizophrenia and/or cocaine
      dependence.
AB  - OBJECTIVE: Although little is known about neurocognition in Dual Diagnosis, it
      has been suggested that Schizophrenia (SZ) patients with comorbid substance use
      belong to a subgroup with lower genetic vulnerability to develop SZ and,
      consequently, they show better executive and social premorbid functioning. The
      first aim of this study was to assess the executive functioning, and the second
      one was to explore the effect of age of onset of substance use in neurocognition
      in SZ patients with cocaine dependence. METHODS: The total sample consisted of 95
      male patients, aged 20 to 60 years, divided in three groups: one group with SZ
      and cocaine dependence (SZ+; n = 30), another group with SZ without cocaine
      dependence (SZ-; n = 30), and a control group with cocaine dependence without
      psychiatric comorbidity (COC; n = 35). RESULTS: We found a better executive
      functioning in both SZ+ and COC than SZ-. We observed a worse performance of SZ+
      patients compared with COC in cognitive set-shifting regardless the age of onset
      of consumption. CONCLUSIONS: The results agree with the hypothesis of a lower
      genetic vulnerability in SZ+ patients to develop psychosis compared with SZ-, who
      develop it without any additional trigger. However, future research is needed to
      clarify the current knowledge gaps.

PMID- 23166053
TI  - Choice of the denominator in case population studies: event rates for
      registration for liver transplantation after exposure to NSAIDs in the SALT study
      in France.
AB  - PURPOSE: The effect of denominator options on event rates was tested on the
      French part of the Study of Acute Liver Transplant (SALT). METHODS: SALT is a
      case population study of acute liver failure registered for transplantation
      (ALFT), exposed to non-steroidal anti-inflammatory drugs (NSAIDs) or non-overdose
      paracetamol, from 2005 to 2007. Population exposure was computed from the
      Intercontinental Medical Services' (IMS) and the French national healthcare
      insurance system's data as the number of defined daily doses (DDDs) sold or
      dispensed and the number of exposed patients. RESULTS: Nine ALFT cases were
      exposed to 10 NSAIDs and 49 to non-overdose paracetamol. NSAID sales ranged from
      0.04 billion (niflumic acid) to 0.5 billion (ibuprofen) DDDs, amounting to 2.5
      billion DDDs for all NSAIDs. The mean per-person exposure ranged from 13.1
      (niflumic acid) to 43.2 (ketoprofen) DDDs, reaching 60.5 DDDs for any NSAID. The
      number of users ranged from 2 million (niflumic acid) to 13 million (ibuprofen),
      which was 26.6 million for all NSAIDs. The ALFT rates per billion DDDs ranged
      from 0 to 26 for individual NSAIDs and amounted to 4.6 for all NSAIDs. The ALFT
      rates per billion DDDs were inversely correlated with the average per-patient
      exposure (R(2)  = 0.935, p = 0.0016). The ALFT rates per million users ranged
      from 0.31 to 0.49, which was 0.41 for all NSAIDs, with no difference between
      drugs and no effect of mean per-patient exposure (R(2)  = 0.01, p = 0.9). Whether
      measured per DDD or per user, the event rate with paracetamol was three to five
      times higher than with NSAIDs. CONCLUSION: ALFT risk with NSAID seems to be user
      dependent rather than person-time (exposure) dependent. Choosing the wrong
      denominator in case population studies might give erroneous results.

PMID- 23166054
TI  - Incidental findings in genetic research and clinical diagnostic tests: a
      systematic review.
AB  - Incidental findings arise when clinically relevant genetic information about a
      research participant or patient is identified outside the scope of the original
      research objective or diagnostic test being performed. These findings can relate
      to carrier status for a heritable condition, misattributed paternity or increased
      susceptibility to a medical condition. The decision whether to disclose these
      findings to the research subject or patient is underpinned by many ethical,
      moral, and potentially legal considerations. There is an urgent need for
      definitive guidelines for researchers and healthcare professionals. We performed
      a systematic review of the relevant literature concerning the disclosure of
      incidental findings, based on the Preferred Reporting Items for Systematic
      Reviews and Meta-Analyses recommendations, using the prescribed flowchart and
      checklist. At initial screening, 473 articles were retrieved. The inclusion and
      exclusion criteria aimed at obtaining data that were relevant and of sufficient
      quality were applied and a total of four relevant studies were identified,
      comprising 2,680 individual participants and 1,023 guidance documents. Major
      themes emerging from the included articles include patient autonomy, patient
      welfare, harmful secrets, and genetic literacy. The lack of relevant studies
      emphasizes the urgent need for empirical investigations into the disclosure or
      non-disclosure of genetic incidental findings, and the provision of guidelines to
      assist healthcare professionals and researchers.

PMID- 23166055
TI  - Hydrogels as feeder-free scaffolds for long-term self-renewal of mouse induced
      pluripotent stem cells.
AB  - Expanding undifferentiated induced pluripotent stem (iPS) cells in vitro is a
      basic requirement for application of iPS cells in both fundamental research and
      clinical regeneration. In this study, we intended to establish a simple, low cost
      and efficient method for the long-term self-renewal of mouse induced pluripotent
      stem (miPS) cells without using feeder-cells and adhesive proteins. Three
      scaffolds were selected for the long-term subculture of miPS cells over two
      months starting from passages 14 to 29: 1) a gelatin coated polystyrene (Gelatin
      PS) that is a widely used scaffold for self-renewal of mouse embryonic stem (mES)
      cells; 2) a neutral hydrogel poly(N,N-dimethylacrylamide) (PDMAAm); and 3) a
      negatively charged hydrogel poly(2-acrylamido-2-methyl-propane sulfonic acid
      sodium salt) (PNaAMPS). Each passaged miPS cells on these scaffolds were
      cryopreserved successfully and the revived cells showed high viability and
      proliferation. The passaged miPS cells maintained a high undifferentiated state
      on all three scaffolds and a high level of pluripotency by expressing
      differentiation markers in vitro and forming teratomas in SCID mice with
      derivatives of all three germ layers. Compared to Gelatin-PS, the two hydrogels
      exhibited much better self-renewal performance in terms of high proliferation
      rate and level of expression of undifferentiated gene markers as well as
      efficiency in pluripotent teratoma formation. Furthermore, the PNaAMPS hydrogel
      demonstrated a slightly higher efficiency and simpler operation of cell expansion
      than the PDMAAm hydrogel. To conclude, PNaAMPS hydrogel is an excellent feeder
      free scaffold because of its simplicity, low cost and high efficiency in
      expanding a large number of miPS cells in vitro.

PMID- 23166056
TI  - The bis(allyl)bismuth cation: a reagent for direct allyl transfer by Lewis acid
      activation and controlled radical polymerization.
AB  - A positive effect: the bis(allyl)bismuth cation in
      [Bi(C(3)H(5))(2)(thf)(2)][B(C(6)H(3)Cl(2))(4)] is superior to neutral
      tris(allyl)bismuth in the additive-free allylation of unsaturated C-heteroatom
      functionalities and the controlled living radical polymerization of activated
      olefins.

PMID- 23166057
TI  - The effect of plaster (CaSO4 .1/2H2O) on the compressive strength, self-setting
      property, and in vitro bioactivity of silicate-based bone cement.
AB  - Bone cements have been widely used for orthopedic applications. Previous studies
      have shown that calcium silicon-based bone cements (CSC) were injectable,
      bioactive, biodegradable, and mechanically strong in the long term, while their
      short-term compressive strength was low and setting time was too long. On the
      other hand, plaster (CaSO(4).1/2H(2)O, POP) sets quickly upon contact with water
      and has excellent short-term compressive strength. The aim of this study is to
      prepare CSC/POP composite cements and investigate the effect of POP on the
      compressive strength, setting time, injectability, degradation, and in vitro
      bioactivity of the composite cements. The results have shown that POP content
      plays an important role to modulate the physicochemical property of CSC. The
      addition of POP into CSC significantly decreased the initial and final setting
      time and enhanced the short-term compressive strength and degradation rate. The
      obtained composite cement with 30% POP has been found to possess optimal setting
      time and short-term compressive strength. In addition, the prepared composite
      cements still maintain apatite-mineralization ability in simulated body fluids
      and their ionic extracts have no significant cytotoxicity to L929 cells. The
      results suggested that the addition of POP into CSC is a viable method to improve
      their setting properties and short-term compressive strength. The obtained
      composite cements with the optimized composition of 70% CSC and 30% POP could be
      potentially used for bone repair application.

PMID- 23166058
TI  - ZnO/TiO2 nanocable structured photoelectrodes for CdS/CdSe quantum dot co
      sensitized solar cells.
AB  - Photoelectrode made of nanocable structure of ZnO nanorods (NR) coated with
      TiO(2) nanosheets (NSs) was investigated for CdS/CdSe quantum dot co-sensitized
      solar cells. ZnO NRs prepared solution reaction at 60  degrees C served as the
      backbone for direct electron transport in view of the single crystallinity of the
      ZnO NRs and the high electron mobility of ZnO semiconductor. Anatase TiO(2) NSs
      with the thickness of ~10 nm and the length of ~100 nm were assembled onto the
      surface of ZnO NRs via a solvothermal method. It was found that the thin shell of
      TiO(2) might have remarkable influence on the quantum dot sensitized solar cells
      (QDSCs) through (a) increasing the surface area of ZnO NRs to allow for adsorbing
      more quantum dots (QDs), which led to high short current density, (b) forming an
      energy barrier that hindered the electrons in the ZnO from being back to the
      electrolyte and QDs, and thus, reduced the charge recombination rate, resulting
      in prolonged electron lifetime and enhanced open voltage. In comparison with the
      case of ZnO NRs, the short-circuit current density, open-circuit voltage, fill
      factor and charge recombination resistance of ZnO/TiO(2) nanocable photoelectrode
      increase by 3%, 44%, 48% and 220%, respectively. As a result, a power conversion
      efficiency of 2.7% of QDSCs with core-shell structural nanocable photoelectrode
      has been obtained, which is as much as 230% of that of 1.2% obtained for ZnO NR
      photoelectrode.

PMID- 23166059
TI  - Highly selective dispersion of carbon nanotubes by using
      poly(phenyleneethynylene)-guided supermolecular assembly.
AB  - Isolation of single-walled carbon nanotubes (SWNTs) with specific chirality and
      diameters is critical for achieving optimum performance of SWNTs in various
      applications. A water-soluble pi-conjugated polymer, poly[(m-phenyleneethynylene)
      alt-(p-phenyleneethynylene)], 3, is found to exhibit high selectivity in
      dispersing SWNT (6,5). The polymer's ability to sort out SWNT (6,5) appears to be
      related to the carbon-carbon triple bond, whose free rotation allows a unique
      assembly of chromophores in a helical conformation. The observation is
      consistently supported by fluorescence, Raman, and UV-vis-NIR absorption spectra.
      The intriguing selectivity of 3 to SWNT (6,5), however, is not observed for the
      vinylene analogue polymer 1, showing that the carbon-carbon triple bond could
      play a unique role in sorting out a specific SWNT. The observed selectivity from
      3 could be attributed to a combination of the helical cavity size restrain and
      electronic interaction associated with the local chromophore arrangement. This
      strategy could be expanded for efficient SWNT sorting when the helical
      conformation is further finely tuned.

PMID- 23166060
TI  - Describing perceived stigma against Alzheimer's disease in a general population
      in France: the STIG-MA survey.
AB  - BACKGROUND: Alzheimer's disease (AD) causes progressive loss of memory and
      disability, especially in older people. As worldwide population grows older, AD
      is responsible for an important social and economical burden in many nations.
      People suffering from AD may experience health-related stigma that influences
      their attitudes towards seeking assistance. The STIG-MA survey describes
      perceived stigma against AD in a French population. METHODS: The STIG-MA
      questionnaire was completed anonymously by people attending an awareness campaign
      about AD in Creuse, France, in September 2010. Participants answered 10 questions
      about how they would feel or react if they had AD. Stigma scores were compared by
      age, activity, and interest in AD. RESULTS: Thirty-three percent of people
      attending the campaign filled out the survey. Most were women (85%) younger than
      50 years (59%); 10% were older people (older than 75 years). Twenty-one percent
      worked in health or social fields. Interest in AD was professional (48%), related
      to family (41%), or personal (11%). Professionals in health fields expressed the
      highest levels of stigma (p = 0.02). Low stigma was most frequent in older people
      (p = 0.05). Type of interest did not influence stigma. Shame, loss of self
      esteem, and fear of exclusion were expressed the most. CONCLUSION: The STIG-MA
      survey confirms that AD is a stigmatizing condition in France. The difference
      between perceived stigma of older people, those most exposed to AD, and that of
      health professionals may influence attitudes towards screening and care. Further
      studies of perceived stigma in these populations are necessary to adapt
      intervention strategies.

PMID- 23166061
TI  - Sociodemographic factors influencing the use of injections in South Korean
      outpatient care.
AB  - PURPOSE: This study explored the relationship between sociodemographic factors
      and injection utilization in South Korea. METHODS: We conducted a retrospective
      cross-sectional analysis using 2009 prescription claims for Korean National
      Health Insurance beneficiaries. We analyzed the utilization, costs, and
      proportion of injections in the insured market for oral-injection dual-dose-form
      ingredients (DFIs). We included outpatients who were prescribed DFIs with no age
      limits. Descriptive analysis and multivariate logistic regression were performed
      to evaluate the predictive factors of injection use. RESULTS: Injections
      accounted for about 5% of outpatient utilization and costs of the study drugs.
      The odds of having injections were 1.3-1.6 times higher among those patients who
      are 70 years and older compared with those in the 20s, in smaller-sized hospitals
      and clinics than that in larger, and among medical institutions in rural areas
      than those in the capital area. The odds of having injections were increased
      stepwise for the age groups of 30-69 years. Injections were more likely to be
      prescribed for systematic hormonal preparations and drugs for the musculoskeletal
      system. CONCLUSIONS: The use of injections was higher among older groups, among
      smaller medical institutions, and among institutions in rural areas in Korean
      outpatient care. The difference between prescribing defined daily doses and
      prescribing rate for injections of the audit reports implies that Korean doctors
      prescribed injections often, but small doses for momentary effects in outpatient
      settings. Further studies are required to uncover the underlying causes of the
      high prevalence of injection use in older or rural populations and smaller
      institutions.

PMID- 23166062
TI  - Type 2 diabetes patients educated by other patients perform at least as well as
      patients trained by professionals.
AB  - BACKGROUND: Diabetes education can improve the quality of care of people with
      diabetes, but many organizations are not equipped to manage its implementation.
      Involving people with diabetes in the education process can overcome the problem.
      Thus, we compared clinical, metabolic and psychological outcomes in people with
      type 2 diabetes 1 year after attending a structured diabetes education programme
      implemented by professional educators versus the same programme implemented by
      trained peers with diabetes that also provided ongoing peer support. METHODS:
      People with type 2 diabetes (25-75 years) were randomly assigned to attend a 4
      week structured diabetes education course delivered by professional educators
      (control) or previously trained peers (peer). Peers also received continuing
      psychological support, including examples on how to apply diabetes knowledge in
      daily life via weekly peer cellular phone calls and bimonthly face-to-face
      interviews in small groups (ten patients), using a structured questionnaire
      related to the patient's clinical, metabolic and psychological progress.
      Identical outcome data from both groups were used for follow-up. RESULTS: Both
      groups had a comparable positive effect on clinical, metabolic and psychological
      indicators immediately following the programme. Over the following year, peer
      educated subjects had lower A(1C) and systolic blood pressure and showed higher
      adherence to physical activity and better control of hypoglycaemic episodes.
      CONCLUSION: The non-inferiority of the peer outcomes and the mentioned
      improvements in this group suggest that volunteer trained peer educators and
      ongoing support can be successful. This approach provides an effective
      alternative method of education, especially in areas with limited availability of
      professionals and economic resources.

PMID- 23166063
TI  - An emerging phenotype of interstitial 15q25.2 microdeletions: clinical report and
      review.
AB  - Interstitial deletions of chromosome 15q25.2 are rare. To date, only nine
      patients with microdeletions within this chromosomal region have been described.
      Here, we report on a girl with severe speech and psychomotor delay, behavioral
      problems and mild dysmorphic features with a 1.6 Mb deletion in 15q25.2 region.
      In order to study the parental origin of the rearrangement, we analyzed selected
      SNPs in the deleted area in the patient and her parents, showing Mendelian
      incompatibilities suggesting a de novo deletion on the chromosome of maternal
      origin. By comparing the clinical and molecular features of our patient with five
      previously reported cases of an overlapping deletion, we suggest that 15q25.2
      deletion is an emerging syndrome characterized by a distinct although variable
      spectrum of clinical manifestations, including mild dysmorphic features,
      neurodevelopmental delay, and a recognizable pattern of congenital malformation.
      Furthermore, our patient is the second one in which a behavioral phenotype
      characterized by hyperactivity, anxiety, and autistic features was reported,
      indicating that these features might be part of this new syndromic condition.
      Breakpoints of the deletion in the patient reported here are useful to better
      define the smallest region of overlap (SRO) among all the patients. Selected
      genes that are present in the hemizygous state and which might be important for
      the phenotype of these patients, are discussed in context of the clinical
      features. In conclusion, our patient increases the knowledge about the molecular
      and phenotypic consequences of interstitial 15q25.2 deletions, highlighting that
      deletions of this region may be responsible for a new microdeletion syndrome.

PMID- 23166064
TI  - A mixed co-culture of mesenchymal stem cells and transgenic chondrocytes in
      alginate hydrogel for cartilage tissue engineering.
AB  - To regenerate articular cartilage tissue from degeneration and trauma, synovial
      mesenchymal stem cells (SMSCs) were used in this study as therapeutic progenitor
      cells to induce therapeutic chondrogenesis. To accomplish this, chondrocytes pre
      transduced with adenoviral vectors carrying the transforming growth factor (TGF)
      beta3 gene were selected as transgenic companion cells and co-cultured side-by
      side with SMSCs in a 3D environment to provide chondrogenic growth factors in
      situ. We adopted a mixed co-culture strategy for this purpose. Transgenic
      delivery of TGF-beta3 in chondrocytes was performed via recombinant adenoviral
      vectors. The mixed co-culture of SMSCs and transgenic chondrocytes was produced
      in alginate gel constructs. Gene expression in both SMSCs and chondrocytes were
      characterized. Biochemical assays in vitro and in vivo showed that release of TGF
      beta3 from transgenic chondrocytes not only induced SMSC differentiation into
      chondrocytic cells but also preserved the chondrocytic phenotype of chondrocytes
      from suspected dedifferentiation. As a result, this mixed co-culture strategy in
      conjunction with TGF-beta3 gene delivery could be a promising approach in
      cartilage tissue engineering.

PMID- 23166065
TI  - A polymacrocyclic oligoarylamine with a pseudobeltane motif: towards a
      cylindrical multispin system.

PMID- 23166066
TI  - Single- and double-sided chemical functionalization of bilayer graphene.
AB  - An experimental study on the interaction between the top and bottom layer of a
      chemically functionalized graphene bilayer by mild oxygen plasma is reported.
      Structural, chemical, and electrical properties are monitored using Raman
      spectroscopy, transport measurements, conductive atomic force microscopy and X
      ray photoelectron spectroscopy. Single- and double-sided chemical
      functionalization are found to give very different results: single-sided modified
      bilayers show relatively high mobility (200-600 cm(2)  V(-1)  s(-1)  at room
      temperature) and a stable structure with a limited amount of defects, even after
      long plasma treatment (>60 s). This is attributed to preferential modification
      and limited coverage of the top layer during plasma exposure, while the bottom
      layer remains almost unperturbed. This could eventually lead to decoupling
      between top and bottom layers. Double-sided chemical functionalization leads to a
      structure containing a high concentration of defects, very similar to graphene
      oxide. This opens the possibility to use plasma treatment not only for etching
      and patterning of graphene, but also to make heterostructures (through single
      sided modification of bilayers) for sensors and transistors and new graphene
      derivatives materials (through double-sided modification).

PMID- 23166067
TI  - Corrosion behavior of novel Ti-24Nb-4Zr-7.9Sn alloy for dental implant
      applications in vitro.
AB  - Ti-24Nb-4Zr-7.9Sn (TNZS) alloy is a newly developed beta-titanium alloy
      considered suitable for dental implant applications due to its low elastic
      modulus and high strength. The aim of this study was to investigate the corrosion
      behavior of TNZS alloy through a static immersion test in various simulated
      physiological solutions, namely, artificial saliva, lactic acid solution,
      fluoridated saliva, and fluoridated acidified saliva for 7 days. The corrosion
      behavior of commercially pure titanium and Ti-6Al-4V alloy were also examined for
      comparison. The elemental release was measured with inductively coupled plasma
      mass spectroscopy, and the changes of alloy surface were observed with scanning
      electron microscopy (SEM). The test results showed that the quantity of each
      metal element released from TNZS alloy into fluoridated solutions was much higher
      than the solutions without fluoride ions. It was highest in fluoridated acidified
      saliva and lowest in artificial saliva (p < 0.01). The total elemental release
      from TNZS alloy was lower than commercially pure titanium and Ti-6Al-4V alloy in
      the same solution (p < 0.01). SEM micrographs indicated that TNZS alloy possessed
      better corrosion resistant performance. It can be concluded that fluoridated
      solutions have a negative influence on the corrosion behavior of TNZS alloy.
      Compared with commercially pure titanium and Ti-6Al-4V alloy, TNZS alloy
      demonstrates better corrosion resistance in various simulated physiological
      solutions, so it has greater potential for dental implant applications.

PMID- 23166068
TI  - Exploring the validity and statistical utility of a racism scale among Black men
      who have sex with men: a pilot study.
AB  - The primary purpose of this two-phased study was to examine the structural
      validity and statistical utility of a racism scale specific to Black men who have
      sex with men (MSM) who resided in the Washington, DC, metropolitan area and
      Baltimore, Maryland. Phase I involved pretesting a 10-item racism measure with 20
      Black MSM. Based on pretest findings, the scale was adapted into a 21-item racism
      scale for use in collecting data on 166 respondents in Phase II. Exploratory
      factor analysis of the 21-item racism scale resulted in a 19-item, two-factor
      solution. The two factors or subscales were the following: General Racism and
      Relationships and Racism. Confirmatory factor analysis was used in testing
      construct validity of the factored racism scale. Specifically, the two racism
      factors were combined with three homophobia factors into a confirmatory factor
      analysis model. Based on a summary of the fit indices, both comparative and
      incremental were equal to .90, suggesting an adequate convergence of the racism
      and homophobia dimensions into a single social oppression construct. Statistical
      utility of the two racism subscales was demonstrated when regression analysis
      revealed that the gay-identified men versus bisexual-identified men in the sample
      were more likely to experience increased racism within the context of intimate
      relationships and less likely to be exposed to repeated experiences of general
      racism. Overall, the findings in this study highlight the importance of
      continuing to explore the psychometric properties of a racism scale that accounts
      for the unique psychosocial concerns experienced by Black MSM. 

PMID- 23166069
TI  - Once weekly rosuvastatin is useful in statin intolerance.

PMID- 23166070
TI  - No treatment is often the best treatment.

PMID- 23166071
TI  - Barriers to expressing concern about inquiries into homicides by psychiatric
      patients.

PMID- 23166072
TI  - Consider the risks of working in the UAE carefully.

PMID- 23166073
TI  - New citizens' juries in breast screening review are biased.

PMID- 23166074
TI  - Prostitutes I have had.

PMID- 23166075
TI  - Ultrasound guided core biopsy is the diagnostic tool of choice in salivary gland
      swellings.

PMID- 23166076
TI  - The new vicious circle of malnutrition and nutraceuticals.

PMID- 23166077
TI  - Replace clonazepam with an alternative antiepileptic drug to reduce drug misuse.

PMID- 23166078
TI  - Time to debate rapid molecular testing for tuberculosis?

PMID- 23166079
TI  - Reversing the WHO crisis: transparent priority matching of global needs with
      donor objectives.

PMID- 23166080
TI  - Antithrombosis stockings must have non-slip soles.

PMID- 23166081
TI  - European Antibiotic Awareness Day and access to antibiotics.

PMID- 23166082
TI  - Care not health should be centre of more integrated system, former health
      ministers agree.

PMID- 23166083
TI  - Governments are told not to skimp on preventive strategies as health budgets
      fall.

PMID- 23166084
TI  - Belief not science is behind flu jab promotion, new report says.

PMID- 23166085
TI  - Experts urge commissioners to invest in self management courses for patients with
      chronic disease.

PMID- 23166086
TI  - More regulation is not the answer to poor care, ministers are told.

PMID- 23166087
TI  - Assessment of early diabetic renal changes with hyperpolarized [1-(13)
      C]pyruvate.
AB  - BACKGROUND: This experimental study explores a novel magnetic resonance
      imaging/spectroscopic (MRI/MRS) method that measures changes in renal metabolism
      in a diabetic rat model. This hyperpolarized metabolic MRI/MRS method allows
      monitoring of metabolic processes in seconds by >10 000-fold enhancement of the
      MR signal. The method has shown that the conversion of pyruvate to bicarbonate,
      i.e. pyruvate dehydrogenase (PDH) activity, is significantly altered in the
      myocardium already at the onset of diabetes, and the predominant Warburg effect
      is a valuable cancer maker via the lactate dehydrogenase (LDH) activity. We
      hypothesize that a similar change in PDH and LDH could be found in the early
      diabetic kidney. METHODS: In a streptozotocin rat model of type 1 diabetes,
      hyperpolarized (13) C-MRI and blood oxygenation level-dependent (1) H-MRI was
      employed to investigate the changes in renal metabolism in the diabetic and the
      control kidneys in vivo. RESULTS: The diabetic kidney showed a 149% increase in
      the lactate/pyruvate ratio compared with the control rat kidney, whereas the
      bicarbonate/pyruvate ratio was unchanged between the diabetic and the control rat
      kidneys, consistent with literature findings. These metabolic findings paralleled
      a reduced intrarenal oxygen availability as found by blood oxygenation level
      dependent MRI. DISCUSSION: Hyperpolarized (13) C-MRI shows promise in the
      diagnosis and monitoring of early renal changes associated with diabetes, with
      the pyruvate/lactate ratio as an imaging biomarker for regional renal changes.

PMID- 23166088
TI  - Epilepsy due to 20q13.33 subtelomere deletion masquerading as pyridoxine
      dependent epilepsy.
AB  - A cause of antiepileptic medication resistant seizures presenting in neonates and
      young infants is pyridoxine-dependent epilepsy (PDE), an organic aciduria, which
      is due to recessive mutations in the ALDH7A1 gene, resulting in deficiency of
      antiquitin. Since the discovery of molecular basis of this disorder, a few
      patients have been reported with a similar clinical phenotype but without
      evidence of antiqutin dysfunction. We report on a patient who had carried a
      clinical diagnosis of PDE for 7 years, but who was than shown to have normal
      ALDH7A1 sequencing and the absence of biomarkers characteristic of this familial
      epilepsy. Array comparative genomic hybridization (CGH) demonstrated a 1.5-Mb
      terminal deletion of the long arm of chromosome 20, which included deletion of
      the KCNQ2 and CHRNA4 genes, both of which have been associated with specific
      epilepsy syndromes. We suggest that this boy's neonatal epilepsy and
      neurodevelopmental disabilities are secondary to this deletion and that his
      clinical response to pyridoxine was coincidental. This patient's history
      emphasizes the utility of array CGH in the evaluation of children with epilepsy
      of unknown etiology.

PMID- 23166089
TI  - Drugs by numbers: reaction-driven de novo design of potent and selective
      anticancer leads.
AB  - A potent and selective inhibitor of the anticancer target Polo-like kinase 1 was
      found by computer-based molecular design. This type II kinase inhibitor was
      synthesized as suggested by the design software DOGS and exhibited significant
      antiproliferative effects against HeLa cells without affecting nontransformed
      cells. The study provides a proof-of-concept for reaction-based de novo design as
      a leading tool for drug discovery.

PMID- 23166090
TI  - Force-controlled fluidic injection into single cell nuclei.

PMID- 23166091
TI  - In vitro evaluation of dentinal hydraulic conductance and tubule sealing by a
      novel calcium-phosphate desensitizer.
AB  - In the current trend of materials used for dentin hypersensitivity treatment,
      calcium-phosphate-containing desensitizers are expected to have advantages in
      oral environment. A newly formulated desensitizer containing tetracalcium
      phosphate and dicalcium phosphate anhydrous (CPD-100) was evaluated in comparison
      to oxalate containing desensitizer (SS) regarding permeability reduction (PR%) by
      measuring hydraulic conductance on the etched dentin discs in vitro. CPD-100
      exhibited mean PR% of 91%, which significantly increased to 98% after immersion
      in artificial saliva (AS) for 4 weeks (p < 0.001), while SS showed a significant
      decrease from 99% to 93% (p < 0.01). SEM observation showed newly formed
      crystallites on CPD-100 treated dentin, which did not exist in SS treated dentin
      after AS immersion, suggesting that calcium oxalate inhibited formation of new
      calcium-phosphate minerals. Five-minute acid challenge did not significantly
      affect PR% of dentin treated by any of the desensitizers. The energy dispersive X
      ray spectroscopy (EDS) analysis indicated that the formed layer of CPD-100 were
      minerals with similar Ca/P ratio to hydroxyapatite. In conclusion, the newly
      developed calcium-phosphate desensitizer has the potential to exhibit long-term
      stability in the oral environment, owing to its chemical properties that promote
      the crystal growth in salivary fluid.

PMID- 23166092
TI  - Long-term high density lipoprotein infusion ameliorates metabolic phenotypes of
      diabetic db/db mice.
AB  - BACKGROUND: Lower quantity and quality of high density lipoprotein (HDL) are
      important characteristics of type 2 diabetes mellitus. Acute HDL infusion results
      in a greater fall of plasma glucose in diabetes patients. Here, we aim to
      investigate the influence of long-term HDL infusion on metabolic phenotypes of
      diabetic db/db mice. METHODS: High density lipoprotein was introduced to db/db
      mice twice a week for 4 weeks. The phenotypes of the mice were monitored by
      analyzing metabolic parameters. Glycogen analysis was performed with
      amyloglucosidase. The corresponding signaling molecules were detected by western
      blot. RESULTS: Long-term introduction of HDL decreased plasma glucose levels of
      db/db mice. Glycogen deposition was enhanced in gastrocnemius muscle, paralleling
      the elevated glycogen synthase kinase-3 phosphorylation. Meanwhile, increased Akt
      Ser473 and adenosine monophosphate-activated protein kinase phosphorylations were
      detected in the muscle. Moreover, HDL reduced blood glucose and free fatty acids
      and improved pancreatic islet structure and function with increased C-peptide.
      Furthermore, decreased interleukin-6, C-reactive protein, monocyte
      chemoattractant protein-1, resistin, and malondialdehyde, as well as enhanced
      leptin levels were detected in HDL-treated mice. CONCLUSION: Results of the
      present study suggest that long-term HDL infusion has positive therapeutic
      effects on the metabolic disturbances of db/db diabetic mice.

PMID- 23166093
TI  - Editors' preface: microglia--a new era dawns.

PMID- 23166094
TI  - Three polymorphisms in IRF6 and 8q24 are associated with nonsyndromic cleft lip
      with or without cleft palate: evidence from 20 studies.
AB  - Nonsyndromic cleft lip with or without cleft palate (NSCL/P) is one of the most
      common craniofacial malformation in humans. Three polymorphisms, rs2235371 and
      rs642961 in interferon regulatory factor 6 (IRF6), rs987525 on 8q24, have been
      shown to be associated with NSCL/P risk in several studies. However, the
      magnitudes of the association varied between studies. We therefore performed a
      meta-analysis to investigate this relationship. Two authors independently
      extracted information on the characteristics of the eligible studies. Either a
      fixed- or a random-effects model was used to calculate the overall combined risk
      estimates. Overall, 20 published case-control studies were included in the meta
      analysis. We found that rs2235371 A allele had a significantly decreased risk
      (OR: 0.73, 95% CI: 0.61-0.88), whereas rs642961 A allele had a significantly
      increased risk of NSCL/P (OR: 1.44, 95% CI: 1.30-1.59), compared with the G
      allele. For 8q24 rs987525, the A allele was associated with a significantly
      increased risk of NSCL/P, compared with the C allele (OR: 1.71, 95% CI: 1.40
      2.09). Furthermore, in the stratified analysis by ethnicity and types of NSCL/P,
      significant associations were still observed in the subgroups of ethnicity and
      types. Taken together, the results suggest that the IRF6 rs2235371, rs642961, and
      8q24 rs987525 polymorphisms are associated with NSCL/P risk.

PMID- 23166095
TI  - Development of sustained-release antibacterial urinary biomaterials through using
      an antimicrobial as an organic modifier in polyurethane nanocomposites.
AB  - Urinary catheters are among the most frequently used medical devices in clinical
      practice. However, their use is associated with high rates of nosocomial
      infection. This study investigates the use of polyurethane nanocomposites (PUNCs)
      incorporating an antimicrobial agent, chlorhexidine diacetate (CHX), behaving as
      nanoparticle dispersant and model drug/active agent, as sustained-release
      antibacterial biomaterials in urinary devices. A range of PUNCs incorporating
      organically modified silicate (OMS) nanoparticles with CHX was fabricated using a
      solution-cast method. PUNCs with free CHX added into the bulk polymer were also
      made. Materials were assessed for antibacterial activity in an in vitro urinary
      tract (UT) model and release kinetics of CHX was studied. PUNCs demonstrated
      sustained antibacterial activity against Staphylococcus epidermidis in the UT
      model, reaching ~50 days infection-free in materials with 2 wt % free CHX
      loading. Drug-release profiles demonstrated that, compared with microcomposite
      and unfilled polyurethane, the initial burst effect was significantly reduced in
      PUNCs. Prolonged drug release was achieved through incorporation of OMS,
      hypothesized to be due to a combination of barrier properties created by the
      nanoinclusions and strong interactions between CHX and MMT within the PUNCs. Use
      of PUNCs for sustained drug release in long-term urinary applications shows
      promise in addressing catheter-related nosocomial infections.

PMID- 23166096
TI  - Real-time, sensitive, and specific detection of promoter-polymerase interactions
      in gene transcription using a nanoplasmonic sensor.

PMID- 23166097
TI  - Temperature-controlled ionic liquid dispersive liquid-phase microextraction
      combined with HPLC with ultraviolet detector for the determination of fungicides.
AB  - Present study described a simple, environmental benign, easy to operate, and
      determination method for fungicides including thiram, metalaxyl, diethofencarb,
      myclobutanil, and tebuconazole. The method is based on temperature-controlled
      ionic liquid dispersive liquid phase microextraction coupled to HPLC with
      ultraviolet detector. In the enrichment procedure, ionic liquid 1-octyl-3
      methylimidazolium hexafluorophosphate [C(8)MIM][PF(6)] was used as the extraction
      solvent. Variable affecting parameters such as the volume of [C(8)MIM][PF(6)],
      temperature, extraction time, centrifuging time, and salting-out effect have been
      optimized in detail. Under the optimal conditions, this method has been found to
      have good linear relationship in the concentration range of 1.0-100 MUg/L and
      excellent detection sensitivity with LODs (S/N = 3) in the range of 0.32-0.79
      MUg/L. Precisions of proposed method were in the range of 3.7-5.9% for intraday
      and 7.8-11.0% for interday (RSDs, n = 6). The proposed method was used for the
      analysis of real water samples and good spiked recoveries at two different spiked
      levels were achieved in the range of 84.6-102%.

PMID- 23166098
TI  - Zotarolimus-eluting stents among patients with renal impairment undergoing
      percutaneous coronary intervention.

PMID- 23166099
TI  - Closure of perimembranous ventricular septal defects with aneurysmal tissue using
      the Amplazter Duct Occluder I.

PMID- 23166100
TI  - The identification of a high-risk subset for balloon aortic valvuloplasty.

PMID- 23166101
TI  - Provisional transesophageal echocardiography during transcatheter aortic valve
      implantation.

PMID- 23166102
TI  - Use of intraprocedural CT imaging to guide alcohol septal ablation. Combining
      complementary imaging modalities.

PMID- 23166103
TI  - Embolic protection for renal stenting: should it be standard of care?

PMID- 23166104
TI  - Novel strategies for the diagnosis and treatment of arterial access perforations.

PMID- 23166105
TI  - Emotion coupling and regulation in anorexia nervosa.
AB  - OBJECTIVE: The present study sought to investigate emotion regulation strategies
      in people with anorexia nervosa (AN) and whether the theoretical concept of
      'emotion coupling' between anger and disgust could help to explain some of the
      specific eating disorder symptomatology in people with AN. METHOD: This 'emotion
      coupling' hypothesis was tested using a mood induction procedure within
      laboratory conditions, where individuals with AN (n = 22) were matched with
      control participants (n = 19). Participants completed a bank of different
      measures prior to the study, and these included measures of eating pathology,
      core beliefs about the self and others, and emotion regulation strategies. Within
      the experimental part of this study, anger, disgust and body size estimation were
      measured prior to and after an anger induction procedure (i.e., a repeated
      measures design). RESULTS: People with AN demonstrated a significantly more
      internal-dysfunctional way to regulate their emotional states, when compared with
      matched controls. Within the 'emotional coupling' part of the study, participants
      showed a significant increase in levels of disgust and body size estimation
      following an anger induction when compared with matched controls. DISCUSSION: The
      significance of these results was considered in the light of the new Schematic,
      Propositional, Analogical and Associative Representation Systems in eating
      disorders model.

PMID- 23166106
TI  - Endothelial cells (ECs) for vascular tissue engineering: venous ECs are less
      thrombogenic than arterial ECs.
AB  - Primary endothelial cells (ECs) are the preferred cellular source for luminal
      seeding of tissue-engineered (TE) vascular grafts. Research into the potential of
      ECs for vascular TE has focused particularly on venous rather than arterial ECs.
      In this study we evaluated the functional characteristics of arterial and venous
      ECs, relevant for vascular TE. Porcine ECs were isolated from femoral artery
      (PFAECs) and vein (PFVECs). The proliferation rate was comparable for both EC
      sources, whereas migration, determined through a wound-healing assay, was less
      profound for PFVECs. EC adhesion was lower for PFVECs on collagen I, measured
      after 10 min of arterial shear stress. Gene expression was analysed by qRT-PCR
      for ECs cultured under static conditions and after exposure to arterial shear
      stress and revealed differences in gene expression, with lower expression of
      EphrinB2 and VCAM-1 and higher levels of vWF and COUP-TFII in PFVECs than in
      PFAECs. PFVECs exhibited diminished platelet adhesion under flow and cell-based
      thrombin generation was delayed for PFVECs, indicating diminished tissue factor
      (TF) activity. After stimulation, prostacyclin secretion, but not nitric oxide
      (NO), was lower in PFVECs. Our data support the use of venous ECs for TE because
      of their beneficial antithrombogenic profile.

PMID- 23166107
TI  - Characterization of novel akermanite:poly-epsilon-caprolactone scaffolds for
      human adipose-derived stem cells bone tissue engineering.
AB  - In this study, three different akermanite:poly-epsilon-caprolactone (PCL)
      composite scaffolds (wt%: 75:25, 50:50, 25:75) were characterized in terms of
      structure, compression strength, degradation rate and in vitro biocompatibility
      to human adipose-derived stem cells (hASC). Pure ceramic scaffolds [CellCeramTM,
      custom-made, 40:60 wt%; beta-tricalcium phosphate (beta-TCP):hydroxyapatite (HA);
      and akermanite] and PCL scaffolds served as experimental controls. Compared to
      ceramic scaffolds, the authors hypothesized that optimal akermanite:PCL
      composites would have improved compression strength and comparable
      biocompatibility to hASC. Electron microscopy analysis revealed that PCL
      containing scaffolds had the highest porosity but CellCeramTM had the greatest
      pore size. In general, compression strength in PCL-containing scaffolds was
      greater than in ceramic scaffolds. PCL-containing scaffolds were also more stable
      in culture than ceramic scaffolds. Nonetheless, mass losses after 21 days were
      observed in all scaffold types. Reduced hASC metabolic activity and increased
      cell detachment were observed after acute exposure to akermanite:PCL extracts
      (wt%: 75:25, 50:50). Among the PCL-containing scaffolds, hASC cultured for 21
      days on akermanite:PCL (wt%: 75:25) discs displayed the highest viability,
      increased expression of osteogenic markers (alkaline phosphatase and osteocalcin)
      and lowest IL-6 expression. Together, the results indicate that akermanite:PCL
      composites may have appropriate mechanical and biocompatibility properties for
      use as bone tissue scaffolds.

PMID- 23166108
TI  - Cytologic diagnosis of thyroid-like follicular carcinoma of the kidney: a case
      report.
AB  - Thyroid-like follicular carcinoma of the kidney (TLFCK) is a recently described
      subtype of renal-cell carcinoma that is not currently included in the World
      Health Organization classification. Few sporadic case reports and one series have
      been reported with emphasis on histopathologic features. However, cytological
      features have not been described in the literature to date. A 34-year-old male
      presented with a renal mass. An intraoperative smear preparation of the tumor
      revealed a hypercellular smear with cells arranged in sheets without any
      follicular, papillary, or acinar arrangement. The most striking feature was the
      presence of acellular eosinophilic material associated with the neoplastic
      epithelial cells in the background of the smear. Individual tumor cells were
      oval, round, and plasmacytoid with mild nuclear pleomorphism, finely stippled
      nuclear chromatin, and inconspicuous nucleoli with moderate amount of
      eosinophilic cytoplasm and rare nuclear grooves. It was unclear at the time of
      the intraoperative assessment of the smear if the acellular eosinophilic material
      represented metachromatic matrix-like extracellular material, mucin, colloid,
      amyloid, or hyaline material. The differential diagnoses included a primary renal
      cell carcinoma versus a metastatic tumor. Subsequent histopathologic examination
      was diagnostic of a rare, recently described primary neoplasm of the kidney
      called TLFCK. This work is a retrospective evaluation of the cytological features
      of TLFCK. It is important for cytopathologists to be aware of this entity and its
      cytological features to render a correct diagnosis for adequate management of
      these patients.

PMID- 23166109
TI  - Novel naturally crosslinked electrospun nanofibrous chitosan mats for guided bone
      regeneration membranes: material characterization and cytocompatibility.
AB  - Guided bone regeneration (GBR) barrier membranes are used to prevent soft tissue
      infiltration into the graft space during dental procedures that involve bone
      grafting. Chitosan materials have shown promise as GBR barrier membranes, due to
      their biocompatibility and predictable biodegradability, but degradation rates
      may still be too high for clinical applications. In this study, chitosan GBR
      membranes were electrospun using chitosan (70% deacetylated, 312 kDa, 5.5 w/v%),
      with or without the addition of 5 or 10 mm genipin, a natural crosslinking agent,
      in order to extend the degradation to meet the clinical target time frame of 4-6
      months. Membranes were evaluated for fibre diameter, tensile strength,
      biodegradation rate, bond structure and cytocompatibility. Genipin addition, at 5
      or 10 mm, resulted in median fibre diameters 184, 144 and 154 nm for
      uncrosslinked, 5 mm and 10 mm crosslinked, respectively. Crosslinking, examined
      by Fourier transform infrared spectroscopy, showed a decrease in N-H stretch as
      genipin levels were increased. Genipin-crosslinked mats exhibited only 22%
      degradation based on mass loss, as compared to 34% for uncrosslinked mats at 16
      weeks in vitro. The ultimate tensile strength of the mats was increased by 165%
      to 32 MPa with 10 mm crosslinking as compared to the uncrosslinked mats. Finally,
      genipin-crosslinked mats supported the proliferation of SAOS-2 cells in a 5 day
      growth study, similar to uncrosslinked mats. These results suggest that
      electrospun chitosan mats may benefit from genipin crosslinking and have the
      potential to meet clinical degradation time frames for GBR applications.

PMID- 23166110
TI  - Adenomatoid mesothelioma with intranuclear inclusion bodies: a case report with
      cytological and histological findings.
AB  - We report a very unusual cytologic feature, intranuclear inclusion bodies, in
      mesothelioma of a predominantly adenomatoid type. The patient, a 57-year-old
      woman, was presented with dyspnea and right pleural effusion. Pleural aspiration
      cytology revealed many cohesive ball-like clusters, with a tubular pattern,
      composed of small atypical cells displaying a high-nuclear-cytoplasmic ratio.
      They had a nuclear groove and irregular intranuclear inclusion bodies. Right lung
      partial resection with thoracoscopy revealed that a white tumor had proliferated
      along the pleural surface at S(8) . Histology revealed nodular tumor cells
      forming dilated structures mixed with small tubular or glandular structures
      similar to those seen in benign adenomatoid tumors. These tumor cells had invaded
      peripheral lung tissues. Such inclusion bodies have not been reported earlier in
      mesothelioma. On the basis of this observation, we propose that the adenomatoid
      type of malignant mesothelioma be added to the differential diagnosis of
      malignant effusions when tumor cells with nuclear grooves and intranuclear
      inclusions are found in pleural aspiration cytology.

PMID- 23166111
TI  - Pulmonary neuroendocrine tumors: an entity in search of cytologic criteria.
AB  - Pulmonary neuroendocrine tumors (PNET) are histologically subclassified into
      typical carcinoid (TC), atypical carcinoid (AC), large cell neuroendocrine
      carcinoma (LCNEC), and small cell carcinoma (SCLC). The criteria for
      subclassification in cytological specimens are not well defined. In this study,
      we reviewed histologically confirmed 18 TC, 8 AC, 10 LCNEC, and 10 SCLC cytologic
      specimens from 45 patients. The following features were reviewed: small clusters,
      geographic sheets, trabecular structures, pseudo-rosettes, single cells,
      doublets, triplets or short cords, papillary-like structures, capillary
      vasculatures, necrosis, smear background, cell size, cell pleomorphism, amount of
      cytoplasm, plasmacytoid cells, spindle cells, nuclear atypia, molding, palisading
      and smearing, chromatin textures, nucleoli, and mitotic figure count. Based on
      our results, geographic clusters and necrosis were often seen in LCNEC and SCLC;
      while AC only showed scattered single cell necrosis. TC and AC commonly exhibited
      trabecular structures. Papillary-like structures and capillary vasculature were
      only present in TC, AC, and LCNEC. Cells forming doublets, triplets, and short
      cords were more commonly seen in SCLC and rarely seen in other entities.
      Plasmacytoid and spindle cells were only seen in TC and AC. Nuclear smearing was
      not identified in TC, rare in AC, focally present in LCNEC and obvious in SCLC.
      Mitotic figures were nearly absent in TC, <=5/10 HPF in AT, and >=10/10 HPF in
      SCLC. LCNEC showed a wide span of mitotic count ranging between 2 and 16/10 HPF.
      In this study, we propose a set of cytological features that are essential for
      subclassification of PNETs in cytologic specimens.

PMID- 23166112
TI  - Cytological features of clear cell thyroid tumors, including a papillary thyroid
      carcinoma with prominent hobnail features.
AB  - Primary thyroid tumors with extensive clear cell changes are extremely rare. More
      than 10,000 ultrasound-guided thyroid fine needle aspirations examined over a
      period of 17 years by the first author, only one of the 530 (<0.2%) papillary
      thyroid carcinomas (PTCs) and three of the 42 (7.1%) follicular thyroid
      carcinomas (FTCs) had extensive cytoplasmic clearing. Thyroidectomies were
      performed for these cases at four different hospitals in New York City. Final
      pathology was available for review in each of the four cases. Histology showed a
      1.5-cm PTC with prominent hobnail features and clear cell change in a 31-year-old
      woman, a 4.3-cm FTC without angioinvasion in a 31-year-old woman, a 4.5-cm
      angioinvasive FTC in a 45-year-old man, and a 2-cm FTC with extensive
      angioinvasion in a 41-year-old woman with McCune-Albright syndrome (previously
      published). On ultrasound, the FTCs were solid circumscribed nodules and the PTC
      had an irregular margin. In these cases, the etiology for the cytoplasmic
      clearing included accumulation of glycogen in the PTC, accumulation of vesicles
      in two of the FTCs, and accumulation of lipid droplets in a FTC with extensive
      angioinvasion. Review of the cytologic literature showed 17 cases of follicular
      derived thyroid tumors with extensive clear cell change. To the best of our
      knowledge, this is the first cytologic report of PTC with hobnail features and
      extensive clear cell change.

PMID- 23166113
TI  - Reply to Dr Onal: the importance of serum angiotensin-converting enzyme level in
      chronic hepatitis B.

PMID- 23166114
TI  - New therapeutic pathways in the RAS.

PMID- 23166115
TI  - Eml4-alk-positive lung adenocarcinoma with signet-ring cells.

PMID- 23166116
TI  - Pseudofungal tap water contaminants in sputum cytology.

PMID- 23166117
TI  - Cognitive functioning in pediatric transverse myelitis.
AB  - BACKGROUND: Transverse myelitis (TM) is an inflammatory disease of the spinal
      cord. In pediatric TM patients, cognitive and psychological problems have been
      described only anecdotally. OBJECTIVES: Study aims include describing cognitive
      dysfunction among a cohort of pediatric TM patients as well as qualitatively
      exploring the impact of depression, medication, and fatigue on cognitive
      functioning. METHODS: Twenty-four consecutive TM patients referred to a pediatric
      demyelinating diseases clinic completed neuropsychological screening. Means,
      standard deviations (SD), and percentages of patients performing at or below 1.0,
      1.5, and 2.0 SD from the mean on tests administered are presented. RESULTS: Means
      were generally average across domains; however, scores ranged widely across
      subjects within each domain. The highest rate of deficits was observed in fine
      motor speed/dexterity. Slightly higher frequencies of impairment were observed in
      attention and memory as compared to processing speed and verbal fluency. Results
      did not suggest a clear association between cognitive problems and depression or
      medication use but did suggest that fatigue may impact cognitive functioning.
      CONCLUSIONS: This study is the first to document cognitive deficits in pediatric
      TM and raises questions regarding our understanding of the central nervous system
      (CNS) injury associated with TM. Findings warrant further exploration of
      neuropsychological outcomes in TM to inform appropriate intervention.

PMID- 23166118
TI  - Recognition performance differentiates between elderly patients in the long term
      course of secondary progressive multiple sclerosis and amnestic mild cognitive
      impairment.
AB  - BACKGROUND: Cognitive impairment is a common symptom of multiple sclerosis (MS),
      but little is known about cognitive decline in patients in the long-term course
      of progressive MS. Because advancing age is the most significant risk factor for
      Alzheimer's Disease (AD), AD-related pathology must be considered in elderly
      patients with MS. Amnestic mild cognitive impairment (aMCI) represents the
      prodromal phase of AD with subjects showing memory impairment that does not
      improve with recognition testing. OBJECTIVE: We sought to identify disease
      dependent deterioration patterns by comparing elderly patients with secondary
      progressive MS (SPMS) and with aMCI using the Consortium to Establish a Registry
      for Alzheimer's Disease test battery. METHODS: This study included 120 age-,
      education- and gender-matched participants, including healthy controls (n=40),
      SPMS patients (n=40), and aMCI patients (n=40). RESULTS: Episodic memory deficits
      appeared in the long-term course of SPMS. Deficits were associated with
      deterioration of executive function, but not impairment of memory storage as
      recognition was preserved in SPMS in contrast to the patients with aMCI.
      CONCLUSION: Through neuropsychological testing, MS-related episodic memory
      impairment due to deteriorated executive function can be distinguished from AD
      related encoding and storage deficits. Hence, neuropsychological testing may help
      to identify AD-related pathology in SPMS patients.

PMID- 23166119
TI  - Heat sensitive persons with multiple sclerosis are more tolerant to resistance
      exercise than to endurance exercise.
AB  - BACKGROUND: Heat sensitivity (HS) is reported by 58% of all persons with multiple
      sclerosis (MS), causing symptom exacerbation possibly limiting exercise
      participation. OBJECTIVE: The purpose of this study was to test the hypotheses
      that (a) a relationship between exercise-induced changes in core-temperature
      (C(temp)) and changes in symptom intensity exists, and (b) that resistance
      exercise (RE), as a consequence of a minor increase in core temperature, will
      induce a lesser worsening of symptoms than endurance exercise (EE) in HS persons
      with MS. METHODS: On two separate days, 16 HS persons with MS randomly completed
      a session of RE and EE, or EE and RE, respectively. Testing was conducted pre,
      post and one hour after exercise and consisted of Visual Analogue Scale (VAS)
      scoring (fatigue, spasticity, pain, strength, walking and balance), the 5-time
      sit-to-stand (5STS), the Multiple Sclerosis Functional Composite (MSFC) and Body
      Sway. Composite scores describing average subjective symptom intensity (SI) and
      total number of symptoms (SN) were calculated from VAS scores. RESULTS: C(temp)
      (0.9+/-0.4 degrees C vs 0.3+/-0.1 degrees C, p<0.001), SI (1.7+/-1.9 cm vs 0.6+/
      1.5 cm, p<0.05) and SN (1.6+/-1.9 vs 0.6+/-2.1, p<0.05) increased significantly
      more during EE than RE. Changes in C(temp) correlated to changes in SI (r=0.50,
      p<0.01). No differences were observed in 5STS, MSFC and Body Sway scores after EE
      when compared to RE. CONCLUSION: An exercise-induced increase in C(temp) is
      associated with increased number and severity of perceived symptoms in HS persons
      with MS. Based on these findings it is expected that HS persons with MS do
      tolerate RE better than EE.

PMID- 23166120
TI  - A preliminary prospective study of nutritional, psychological and combined
      therapies for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) in a
      private care setting.
AB  - BACKGROUND: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a
      condition characterised by severe and persistent fatigue, neurological
      disturbances, autonomic and endocrine dysfunctions and sleep difficulties that
      have a pronounced and significant impact on individuals' lives. Current National
      Institute for Health and Clinical Excellence guidelines within the UK suggest
      that this condition should be treated with cognitive behavioural therapy and/or
      graded exercise therapy, where appropriate. There is currently a lack of an
      evidence base concerning alternative techniques that may be beneficial to those
      with ME/CFS. OBJECTIVES: This study aimed to investigate whether three modalities
      of psychology, nutrition and combined treatment influenced symptom report
      measures in those with ME/CFS over a 3-month time period and whether there were
      significant differences in these changes between groups. DESIGN AND SETTING: This
      is a preliminary prospective study with one follow-up point conducted at a
      private secondary healthcare facility in London, UK. PARTICIPANTS: 138
      individuals (110 females, 79.7%; 42 participants in psychology, 44 in nutrition
      and 52 in combined) participated at baseline and 72 participants completed the
      battery of measures at follow-up (52.17% response rate; 14, 27 and 31
      participants in each group, respectively). OUTCOME MEASURES: Self-reported
      measures of ME/CFS symptoms, functional ability, multidimensional fatigue and
      perceived control. RESULTS: Baseline comparisons showed those in the combined
      group had higher levels of fatigue. At follow-up, all groups saw improvements in
      fatigue, functional ability and symptomatology; those within the psychology group
      also experienced a shift in perceived control over time. CONCLUSIONS: This study
      provides early evidence that psychological, nutritional and combined techniques
      for the treatment of ME/CFS may influence symptomatology, fatigue, function and
      perceived control. However, these results must be viewed with caution as the
      allocation to groups was not randomised, there was no control group and the study
      suffered from high drop-out rates.

PMID- 23166121
TI  - The essential elements of health impact assessment and healthy public policy: a
      qualitative study of practitioner perspectives.
AB  - OBJECTIVES: This study uses critical realist methodology to identify the
      essential and contingent elements of Health Impact Assessment (HIA) and Healthy
      Public Policy (HPP) as operationalised by practitioners. DESIGN: Data collection
      qualitative interviews and a workshop were conducted with HIA and HPP
      practitioners working in differing contexts. DATA ANALYSIS: Critical realist
      analytical questions identified the essential elements of HIA and HPP, the
      relationship between them, and the influences of public policy and other
      contingencies on the practice of both. PARTICIPANTS: Nine interviews were
      conducted with purposively sampled participants working in Europe, USA and
      Australasia. 17 self-selected participants who worked in Europe, South East Asia
      and Australasia attended the workshop. RESULTS: The results clarify that HIA and
      HPP are different but mutually supporting. HIA has four characteristics:
      assessing a policy proposal to predict population health and equity impacts, a
      structured process for stakeholder dialogue, making recommendations and flexibly
      adapting to the policy process. HPP has four characteristics: concern with a
      broad definition of health, designing policy to improve people's health and
      reduce health inequities, intersectoral collaboration and influencing the policy
      cycle from inception to completion. HIA brings to HPP prediction about a policy's
      broad health impacts, and a structured space for intersectoral engagement, but is
      one approach within a broader suite of HPP activities. Five features of public
      policy and seven contingent influences on HIA and HPP practice are identified.
      CONCLUSIONS: This study clarifies the core attributes of HIA and HPP as separate
      yet overlapping while subject to wider influences. This provides the necessary
      common language to describe the application of both and avoid conflated
      expectations of either. The findings present the conceptual importance of public
      policy and the institutional role of public health as distinct and important
      influences on the practice of HIA and HPP.

PMID- 23166122
TI  - Linking road casualty and clinical data to assess the effectiveness of mobile
      safety enforcement cameras: a before and after study.
AB  - OBJECTIVES: To use police STATS19 road casualty data and accident and emergency
      and in-patient information to estimate the impact of mobile safety cameras on the
      cost of treating individuals injured in road traffic collisions. DESIGN: A data
      matching and costing exercise to link casualty and clinical information in a
      'before' and 'after' study of 56 mobile safety cameras. SETTING: The Northumbria
      Police Force area of the UK covering six local authority districts. PARTICIPANTS:
      Slight, serious and fatal casualties involved in road traffic collisions at
      mobile camera sites in the case-study area between April 2001-March 2003 and
      April 2004-March 2006. PRIMARY AND SECONDARY OUTCOME MEASURES: Changes in the
      number and severity of casualties at the mobile camera sites between the 'before'
      and 'after' period that can be attributed to mobile safety camera activity, and
      any impacts these changes had on the 'cost of treatment saved' by the secondary
      healthcare service in the case-study area. RESULTS: Using tariff values for
      accident and emergency and In-patient Health Resource Groups, the impacts of the
      cameras in terms of the 'cost of treatment saved' are in the range L12 500-L15
      000 per annum. However, inconsistencies between databases resulted in
      approximately one-third of the casualties not being matched successfully in the
      clinical databases. The number of closed fractures requiring investigations,
      treatment and follow-up care reduced considerably, although this was offset by an
      increase in head injury contusions and open fractures that require high-cost
      investigations and extensive in-patient care. CONCLUSIONS: Road safety cameras
      could have a significant impact in terms of 'cost of treatment saved'. However,
      it is argued that investigating the impacts of road safety measures in the future
      should be based on Fully Bayesian techniques as they can produce more reliable
      estimates of the effects of regression to mean and general trends in casualty
      statistics.

PMID- 23166123
TI  - Comparing the validity of the Modified Modified Ashworth Scale (MMAS) and the
      Modified Tardieu Scale (MTS) in the assessment of wrist flexor spasticity in
      patients with stroke: protocol for a neurophysiological study.
AB  - INTRODUCTION: Reliable and valid tools must be used to assess spasticity in
      clinical practise and research settings. There is a paucity of literature
      regarding the validity of the Modified Modified Ashworth Scale (MMAS) and the
      Modified Tardieu Scale (MTS). No study, to date, has been performed to compare
      the validity of the MMAS and the MTS. This neurophysiological study protocol will
      compare the validity of the MMAS and the MTS in the assessment of poststroke
      wrist flexor spasticity. METHODS AND ANALYSIS: Thirty-two patients with stroke
      from the University Rehabilitation clinics will be recruited to participate in
      this cross-sectional, non-interventional study. All measurements will be taken in
      the Physical Medicine and Rehabilitation Department of Shafa University Hospital
      in Tehran, Iran. First, wrist flexor spasticity will be assessed clinically using
      the MMAS and MTS. The tests will be applied randomly. For the MTS, the components
      of R1, R2, R2-R1 and quality of muscle reaction will be measured. Second,
      neurophysiological measures of H-reflex latency, H(max)/M(max) ratio, H(slp) and
      H(slp)/M(slp) ratio will be collected from the affected side. The results will be
      analysed using Spearman's rho test or Pearson's correlation test to determine the
      validity of the MMAS and the MTS as well as to compare the validity between the
      MMAS and the MTS. ETHICS AND DISSEMINATION: The Research Council, School of
      Rehabilitation and the Ethics Committee of Tehran University of Medical Sciences
      (TUMS) approved the study protocol.  The study results will be disseminated in
      peer-reviewed publications and presented at international congresses.

PMID- 23166124
TI  - How are drug regimen changes during hospitalisation handled after discharge: a
      cohort study.
AB  - OBJECTIVES: To investigate drug regimen changes during hospitalisation and
      explore how these changes are handled after patients are transferred back into
      the care of their general practitioners (GPs). DESIGN: Cohort study. SETTING:
      Patients in this multicentre study had undergone at least one change in their
      drug regimens at discharge from the general medicine departments at six hospitals
      in Norway. These changes were altered doses, discontinuation of drugs or start of
      new drugs. Clinical pharmacists visited the patients' GPs 4-5 months after
      patient discharge and recorded any additional drug regimen changes. RESULTS: In
      total, 105 patients (mean age 76.1 years, 54.3% women) completed the study. On
      average, they used 5.6 drugs at admission (range 0-16) and 7.6 drugs at discharge
      (range 1-17). On average, 4.4 drug changes per patient (SD 2.7, range 1-16) were
      made at the hospital, and 3.4 drug changes per patient (SD 2.9, range 0-14)
      within 4-5 months of discharge. Of the 465 drug changes made in hospital, 153
      were changed again after discharge (mean 1.5 per patient, SD 1.8, range 0-13).
      The drug regimens of 90 of these 105 patients were changed after discharge. The
      OR for extensive drug changes after discharge (>= 4 changes) increased
      significantly with the number of drugs used at discharge from hospital (OR=1.29,
      95% CI 1.04 to 1.59). Only 68 of 105 discharge notes contained complete drug
      lists, and only 24 of the discharge notes were received by the GPs within 7 days.
      CONCLUSIONS: In addition to the extensive changes in drug regimens during
      hospitalisation, almost equally extensive changes were made in the initial months
      after discharge. Surveillance of drug regimens is particularly necessary in the
      period immediately after hospital discharge.

PMID- 23166125
TI  - Does cheese intake blunt the association between soft drink intake and risk of
      the metabolic syndrome? Results from the cross-sectional Oslo Health Study.
AB  - OBJECTIVES: A high soft drink intake may promote, whereas intake of cheese may
      reduce risk of the metabolic syndrome (MetS), but will cheese intake blunt the
      soft drink versus MetS association? DESIGN: Cross-sectional study. SETTING: The
      Oslo Health Study. PARTICIPANTS: Among the 18 770 participants of the Oslo Health
      Study there were 5344 men and 6150 women having data on cheese and soft drink
      intake and on risk factors for MetS, except for fasting glucose. The MetSRisk
      index=the weighted sum of triglycerides (TG), systolic blood pressure, diastolic
      blood pressure, waist circumference and body mass index (BMI) divided by high
      density lipoprotein (HDL) were used as a combined risk estimate to examine the
      cheese/soft drink versus MetS interaction, and the SumRisk index was used to
      assess whether increasing intake of soft drinks/cheese would include an
      increasing number of MetS factors being above the cut-off values. We analysed the
      data using non-parametric correlation and analysis of covariance (ANCOVA).
      RESULTS: In all three groups of soft drink intake (seldom/rarely, 1-6
      glasses/week, >=1 glass/day), there was a negative cheese versus MetSRisk
      correlation (p<=0.003), but in the highest intake group the influence of cheese
      seemed to level off, suggesting interaction. However, there was no interaction
      between cheese and soft drinks within the fully adjusted models. Conversely, at
      all four levels of cheese intake, MetSRisk increased with an increasing intake of
      soft drinks (p<=0.001 at all cheese levels). Similar associations were found with
      the SumRisk index. When controlling for a large number of covariates (eg, sex,
      age group, smoking, education, physical activity, intake of fruits/berries and
      vegetables), the above associations prevailed. CONCLUSIONS: Cheese intake blunted
      the association between soft drink intake and MetS, an influence possibly related
      to fatty acid desaturation, or to undetected covariates.

PMID- 23166126
TI  - Geographical variation in certification rates of blindness and sight impairment
      in England, 2008-2009.
AB  - OBJECTIVES: To examine and interpret the variation in the incidence of blindness
      and sight impairment in England by PCT, as reported by the Certificate of Vision
      Impairment (CVI). DESIGN: Analysis of national certification data. SETTING: All
      Primary Care Trusts, England. PARTICIPANTS: 23 773 CVI certifications issued from
      2008 to 2009. MAIN OUTCOME MEASURES: Crude and Age standardised rates of CVI data
      for blindness and sight loss by PCT. METHODS: The crude and age standardised CVI
      rates per 100 000 were calculated with Spearman's rank correlation used to assess
      whether there was any evidence of association between CVI rates with Index of
      Multiple Deprivation (IMD) and the Programme Spend for Vision. RESULTS: There was
      high-level variation, almost 11-fold (coefficient of variation 38%) in
      standardised CVI blindness and sight impairment annual certification rates across
      PCTs. The mean rate was 43.7 and the SD 16.7. We found little evidence of an
      association between the rate of blindness and sight impairment with either the
      IMD or Programme Spend on Vision. CONCLUSIONS: The wide geographical variation we
      found raises questions about the quality of the data and whether there is genuine
      unmet need for prevention of sight loss. It is a concern for public health
      practitioners who will be interpreting these data locally and nationally as the
      CVI data will form the basis of the public health indicator 'preventable sight
      loss'. Poor-quality data and inadequate interpretation will only create confusion
      if not addressed adequately from the outset. There is an urgent need to address
      the shortcomings of the current data collection system and to educate all public
      health practitioners.

PMID- 23166127
TI  - Vaccination coverage and out-of-sequence vaccinations in rural Guinea-Bissau: an
      observational cohort study.
AB  - OBJECTIVE: The WHO aims for 90% coverage of the Expanded Program on Immunization
      (EPI), which in Guinea-Bissau included BCG vaccine at birth, three doses of
      diphtheria-tetanus-pertussis vaccine (DTP) and oral polio vaccine (OPV) at 6, 10
      and 14 weeks and measles vaccine (MV) at 9 months when this study was conducted.
      The WHO assesses coverage by 12 months of age. The sequence of vaccines may have
      an effect on child mortality, but is not considered in official statistics or
      assessments of programme performance. We assessed vaccination coverage and
      frequency of out-of-sequence vaccinations by 12 and 24 months of age. DESIGN:
      Observational cohort study. SETTING AND PARTICIPANTS: The Bandim Health Project's
      (BHP) rural Health and Demographic Surveillance site covers 258 randomly selected
      villages in all regions of Guinea-Bissau. Villages are visited biannually and
      vaccination cards inspected to ascertain vaccination status. Between 2003 and
      2009 vaccination status by 12 months of age was assessed for 5806 children aged
      12-23 months; vaccination status by 24 months of age was assessed for 3792
      children aged 24-35 months. OUTCOME MEASURES: Coverage of EPI vaccinations and
      frequency of out-of-sequence vaccinations. RESULTS: Half of 12-month-old children
      and 65% of 24-month-old children had completed all EPI vaccinations. Many
      children received vaccines out of sequence: by 12 months of age 54% of BCG
      vaccinated children had received DTP with or before BCG and 28% of measles
      vaccinated children had received DTP with or after MV. By 24 months of age the
      proportion of out-of-sequence vaccinations was 58% and 35%, respectively, for BCG
      and MV. CONCLUSIONS: In rural Guinea-Bissau vaccination coverage by 12 months of
      age was low, but continued to increase beyond 12 months of age. More than half of
      all children received vaccinations out of sequence. This highlights the need to
      improve vaccination services.

PMID- 23166128
TI  - Does mild cognitive impairment affect the occurrence of radiographic knee
      osteoarthritis? A 3-year follow-up in the ROAD study.
AB  - OBJECTIVE: To determine whether mild cognitive impairment (MCI) increases the
      risk of occurrence or progression of radiographic knee osteoarthritis (KOA) in a
      general population. DESIGN: Population-based cohort study. SETTING: Residents in
      mountain and seaside areas of Wakayama Prefecture, Japan. PARTICIPANTS: 1690
      participants (596 men, 1094 women; mean age 65.2 years old) were enrolled from
      the large-scale cohort for the Research on Osteoarthritis (OA)/osteoporosis
      Against Disability (ROAD) study initiated in 2005 to investigate epidemiological
      features of OA in Japan. Of these, 1384 individuals (81.9%; 466 men, 918 women)
      completed the second survey including knee radiography 3 years later. PRIMARY
      OUTCOME MEASURES: Radiographic KOA was defined as Kellgren-Lawrence (KL) grade >=
      2 using paired x-ray films. Incidence of KOA during follow-up defined on
      radiographs as KL grade >=2, progression of KOA defined as a higher KL grade
      (either knee) at follow-up compared with baseline. MCI defined as a summary mini
      mental state examination (MMSE) score <=23. Associations between MCI and
      incidence or progression of KOA were analysed. RESULTS: The annual cumulative
      incidence of KOA was 3.3%; for progression of OA it was 8.0%. On logistic
      regression analysis adjusted for age, gender, regional differences, body mass
      index, grip strength (worse side), smoking, alcohol consumption, regular exercise
      and history of knee injury, baseline MMSE summary score was significantly
      associated with the incidence of KOA (+1 MMSE score; OR 0.83, p=0.010). Baseline
      MCI was also significantly associated with the incidence of KOA (vs non
      occurrence of KOA; OR 4.90, p=0.027). There was no significant association
      between MMSE scores, the presence of MCI and progression of KOA (+1 MMSE score;
      OR 0.96, p=0.232; vs non-progression of KOA; OR 1.38, p=0.416). CONCLUSIONS: MCI
      significantly increases the risk of incident radiographic KOA, but not the
      progression of KOA.

PMID- 23166129
TI  - Hospital episode statistics: improving the quality and value of hospital data: a
      national internet e-survey of hospital consultants.
AB  - HYPOTHESIS: Senior hospital clinicians are poorly engaged with clinical coding
      and hospital episode statistics (HES). AIMS:  ? To understand the current level
      of clinical engagement with collection of national data and clinical coding. ? To
      gain the views of frontline staff on proposed improvements to hospital
      statistics. ? To gain an indication of likely clinical engagement in change. ? To
      understand the clinical priority for improvement. DESIGN: Internet e-survey
      accessible from Academy of Royal Medical College Website. SETTING: National
      Health Service (NHS) Trusts. PARTICIPANTS: 1081 NHS hospital consultants and two
      general practitioners who volunteered to take part. RESULTS: 3.4% of the sample
      regularly access HES data; 21% are regularly involved in clinical coding and 6.2%
      meet coding staff at least monthly. 95% would like to access HES data and there
      was a strong support for using this data for appraisal, revalidation and
      improving the quality of patient care. In terms of improvements, 91.9% would be
      prepared to code diagnosis in outpatients given the right tools. The highest
      priority for improvement is clinical validation of diagnostic data. CONCLUSIONS:
      Clinical engagement with coding and access to HES data is poor. However, there is
      professional support for improvement. Clinical requirements should be considered
      in all future developments of national data collection to provide the quality and
      scope of data that is required to deliver the information revolution.

PMID- 23166130
TI  - Life event stress and chronic obstructive pulmonary disease (COPD): associations
      with mental well-being and quality of life in a population-based study.
AB  - OBJECTIVES: To investigate whether life event stress was associated with greater
      psychological distress and poorer quality of life in older individuals with
      chronic obstructive pulmonary disease (COPD), in comparison with their
      counterparts without COPD. DESIGN: Cross-sectional study. PARTICIPANTS: A
      population-based sample (N=497) of individuals aged 65 and above with COPD
      (postbronchodilatation FEV1/FVC<0.70, N=136) and without COPD (N=277).
      MEASUREMENTS: We measured life event stress, depressive symptoms (GDS, Geriatric
      Depression Scale), cognitive symptoms and function (CFQ, Cognitive Failures
      Questionnaire and MMSE, Mini-Mental State Examination), and physical and mental
      health functional status (SF36-PCS, Physical Health Component Summary and SF36
      MCS, Mental Health Component Summary) in participants with and without COPD.
      RESULTS: In two-way analysis of variance controlling for potential confounders,
      life event stress was associated with significant main effects of worse GDS
      (p<0.001), SF36-PCS (p=0.008) and SF36-MCS scores (p<0.001), and with significant
      interaction effects on GDS score (p<0.001), SF36-PCS (p=0.045) and SF36-MCS
      (p=0.034) in participants with COPD, more than in non-COPD participants. The main
      effect of COPD was found for postbronchodilator FEV1 (p<0.001) and cognitive
      symptoms (p=0.02). CONCLUSIONS: Our findings indicate that life event stress was
      associated with more depressive symptoms and worse quality of life in individuals
      with COPD, much more than in those without COPD. Further studies should explore
      the role of cognitive appraisal of stress, coping resources and psycho-social
      support in this relationship.

PMID- 23166131
TI  - Low income is associated with poor adherence to a Mediterranean diet and a higher
      prevalence of obesity: cross-sectional results from the Moli-sani study.
AB  - OBJECTIVES: To examine cross-sectional associations of socioeconomic status (ie,
      income and education) with an adherence to a Mediterranean dietary pattern and
      obesity prevalence. DESIGN: Cross-sectional study on a sample of Italian subjects
      enrolled in the Moli-sani Project, a population-based cohort study. The Italian
      EPIC food frequency questionnaire was used to determine food intake. Adherence to
      a Mediterranean diet (MD) was appraised according to both the Mediterranean score
      elaborated by Trichopoulou (MDS) and the novel Italian Mediterranean Index (IMI)
      and to the a posteriori scores derived from principal component analysis. Four
      income categories were identified. SETTING: Molise region, Italy. PARTICIPANTS:
      13 262 subjects (mean age 53+/-11, 50% men) out of 24 318 citizens (age >=35)
      randomly enrolled in the Moli-sani Project. MAIN OUTCOMES: Dietary patterns and
      risk factors for cardiovascular disease. RESULTS: Household higher income were
      significantly associated with greater adherence to an MD (p<0.0001) and to Olive
      oil and Vegetables dietary pattern in a multivariable model including age, sex,
      daily energy intake, body mass index, physical activity, smoking, alcohol
      consumption, education and marital status. The odds of having the highest
      adherence to an MD clearly increased according to income levels. People having
      the highest income had 54% (95% CI 21% to 97%, MDS) or 72% (95% CI 34% to 121%,
      IMI) higher probability to stick to an MD-like eating pattern than those in the
      lowest-income group. Obesity prevalence was higher in the lowest-income group
      (36%) in comparison with the highest-income category (20%, p<0.0001). Income was
      associated with dietary patterns in all categories of education. CONCLUSIONS: A
      higher income and education are independently associated with a greater adherence
      to MD-like eating patterns and a lower prevalence of obesity.

PMID- 23166132
TI  - Risk factors for injury mortality in rural Tanzania: a secondary data analysis.
AB  - BACKGROUND: Injuries rank high among the leading causes of death and disability
      annually, injuring over 50 million and killing over 5 million people globally.
      Approximately 90% of these deaths occur in developing countries. OBJECTIVES: To
      estimate and identify the risk factors for injury mortality in the Rufiji Health
      and Demographic Surveillance System (RHDSS) in Tanzania. METHODS: Secondary data
      from the RHDSS covering the period 2002 and 2007 was examined. Verbal autopsy
      data was used to determine the causes of death based on the 10th revision of the
      International Classification of Diseases (ICD-10). Trend and Poisson regression
      tests were used to investigate the associations between risk factors and injury
      mortality. RESULTS: The overall crude injury death rate was 33.4/100 000
      population. Injuries accounted for 4% of total deaths. Men were three times more
      likely to die from injuries compared with women (adjusted IRR (incidence risk
      ratios)=3.04, p=0.001, 95% CI (2.22 to 4.17)). The elderly (defined as 65+) were
      2.8 times more likely to die from injuries compared with children under 15 years
      of age (adjusted IRR=2.83, p=0.048, 95% CI (1.01 to 7.93)). The highest frequency
      of deaths resulted from road traffic crashes. CONCLUSIONS: Injury is becoming an
      important cause of mortality in the Rufiji district. Injury mortality varied by
      age and gender in this area. Most injuries are preventable, policy makers need to
      institute measures to address the issue.

PMID- 23166133
TI  - HIV incidence among men who have sex with men in Beijing: a prospective cohort
      study.
AB  - OBJECTIVES: (1) To assess the HIV incidence rate among men who have sex with men
      (MSM) in a large cohort study in Beijing, China and (2) to identify
      sociodemographic and behavioural risk factors of HIV seroconversion among MSM in
      Beijing, China. DESIGN: A prospective cohort study. SETTING: Baseline and follow
      up visits were conducted among MSM in Beijing, China. PARTICIPANTS: A cohort of
      797 HIV-seronegative MSM was recruited from August to December 2009, with follow
      up occurring after 6 and 12 months. PRIMARY AND SECONDARY OUTCOME MEASURES: At
      baseline and follow-up visits, participants reported sociodemographic and sexual
      behaviour information, and were tested for HIV, herpes simplex virus-2 (HSV-2)
      and syphilis with whole blood specimens. Cox regression analysis was used to
      identify factors associated with HIV seroconversion. RESULTS: Most study
      participants (86.8%) were retained by the 12-month follow-up. The HIV, HSV-2 and
      syphilis incidence rates were 8.09 (95% CI 6.92 to 9.26), 5.92 (95% CI 5.44 to
      6.40) and 8.06 (95% CI 7.56 to 8.56) cases per 100 person-years, respectively.
      HIV seroconversion was significantly associated with being <25 years old, having
      <12 years of education, having >1 male sex partner in the past 6 months, and
      being syphilis positive or HSV-2 positive. CONCLUSIONS: The HIV incidence among
      MSM in Beijing is serious. Interventions and treatment of sexually transmitted
      diseases (STD) should be combined with HIV control and prevention measures among
      MSM.

PMID- 23166134
TI  - Childhood motocross truncal injuries: high-velocity, focal force to the chest and
      abdomen.
AB  - OBJECTIVES: To review the need for operative intervention and critical care
      services for motocross truncal injuries in children.   DESIGN COHORT: 
      Retrospective review of patients identified via the hospital trauma registry.
      SETTING: Our Level 1 Pediatric Trauma Center serves five motocross tracks. These
      patients require frequent medical care for injuries. PARTICIPANTS: All patients
      <=17 years of age with truncal injuries sustained during motocross activities,
      between 2000 and 2011, were identified through the trauma registry. PRIMARY AND
      SECONDARY OUTCOME MEASURES: Operative intervention, intensive care unit (ICU)
      admission, length of stay, morbidity and demographics were reviewed. RESULTS:
      Motocross injured 162 children. Thirty (18.5%) were thoracic or abdominal
      injuries. Operative intervention was required in eight (27%) patients. Mean
      injury severity score (ISS) was 11.8. ICU admission was required in 50% and
      average hospital length of stay was 4.1 days. The most common injuries include
      pulmonary contusion, pneumothorax, spleen and liver lacerations. 13% of subjects
      suffered truncal injury from motocross on more than one occasion. CONCLUSIONS:
      Paediatric motocross-related truncal injuries are significant. Surgical
      intervention is required in 27% of patients. The lower ISS incurred from
      motocross combined with high surgical and ICU admission rates suggests focal high
      impact injuries to the chest and abdomen. Despite significant injury, 13% of
      motocross patients suffer recurrent injuries. Parents and children need injury
      prevention education.

PMID- 23166135
TI  - The PREVENT study: a prospective cohort study to identify mid-life biomarkers of
      late-onset Alzheimer's disease.
AB  - INTRODUCTION: Epidemiological studies indicate that significant decreases in the
      incidence of Alzheimer's disease (AD) may be obtained by targeting multiple
      middle-age risk factors. However, as dementia is unlikely to be diagnosed for
      decades, short-term outcome measures are required. AD biomarker changes precede
      clinical symptoms by many years, but their sensitivity to mid-life change remains
      unknown. METHODS AND ANALYSIS: PREVENT is a prospective cohort study examining
      biomarker status at mid-life in at least 150 individuals genetically at high,
      medium or low risk of late-onset AD. Participants are children of individuals
      with or without a diagnosed AD allocated to high, medium and low-risk groups
      according to parental clinical status and ApoE genotype. The biomarkers examined
      over 2 years are plasma and CSF Abeta42 amyloid, Tau and pTau, proinflammatory
      cytokines, acute-phase proteins, medial temporal-lobe atrophy, white matter
      lesion volume, cognitive performance related to transentorhinal and hippocampal
      functioning and hypothalamic-pituitary-adrenal and sympathetic axes regulation.
      ETHICS AND DISSEMINATION: Detected pathologies are communicated to the
      participant's general practitioner with their permission. Risk status by genotype
      would not be revealed. The results of the study would be published in peer
      reviewed journals and validated biomarkers used to construct a randomised
      controlled intervention study.

PMID- 23166136
TI  - Risk factors for stress fracture in female endurance athletes: a cross-sectional
      study.
AB  - OBJECTIVE: To identify psychological and physiological correlates of stress
      fracture in female endurance athletes. DESIGN: A cross-sectional design was used
      with a history of stress fractures and potential risk factors assessed at one
      visit. METHODS: Female-endurance athletes (58 runners and 12 triathletes) aged
      26.0+/-7.4 years completed questionnaires on stress fracture history, menstrual
      history, athletic training, eating psychopathology and exercise cognitions. Bone
      mineral density, body fat content and lower leg lean tissue mass (LLLTM) were
      assessed using dual-x-ray absorptiometry. Variables were compared between
      athletes with a history of stress fracture (SF) and those without (controls; C)
      using chi&sup2;, analysis of variance and Mann-Whitney U tests. RESULTS: Nineteen
      (27%) athletes had previously been clinically diagnosed with SFs. The prevalence
      of current a/oligomenorrhoea and past amenorrhoea was higher in SF than C
      (p=0.008 and p=0.035, respectively). SF recorded higher global scores on the
      eating disorder examination questionnaire (p=0.049) and compulsive exercise test
      (p=0.006) and had higher LLLTM (p=0.029) compared to C. These findings persisted
      with weight and height as covariates. In multivariate logistic regression,
      compulsive exercise, amenorrhoea and LLLTM were significant independent
      predictors of SF history (p=0.006, 0.009 and 0.035, respectively). CONCLUSIONS:
      Eating psychopathology was associated with increased risk of SF in endurance
      athletes, but this may be mediated by menstrual dysfunction and compulsive
      exercise. Compulsive exercise, as well as amenorrhoea, is independently related
      to SF risk.

PMID- 23166137
TI  - Eliciting symptoms interpreted as normal by patients with early-stage lung
      cancer: could GP elicitation of normalised symptoms reduce delay in diagnosis?
      Cross-sectional interview study.
AB  - OBJECTIVES: To investigate why symptoms indicative of early-stage lung cancer
      (LC) were not presented to general practitioners (GPs) and how early symptoms
      might be better elicited within primary care. DESIGN, SETTING AND PARTICIPANTS: A
      qualitative cross-sectional interview study about symptoms and help-seeking in 20
      patients from three south England counties, awaiting resection of LC (suspected
      or histologically confirmed). Analysis drew on principles of discourse analysis
      and constant comparison to identify processes involved in interpretation and
      communication about symptoms, and explain non-presentation. RESULTS: Most
      participants experienced health changes possibly indicative of LC which had not
      been presented during GP consultations. Symptoms that were episodic, or
      potentially caused by ageing or lifestyle, were frequently not presented to GPs.
      In interviews, open questions about health changes/symptoms in general did not
      elicit these symptoms; they only emerged in response to closed questions
      detailing specific changes in health. Questions using disease-related labels, for
      example, pain or breathlessness, were less likely to elicit symptoms than
      questions that used non-disease terminology, such as aches, discomfort or
      'getting out of breath'. Most participants described themselves as feeling well
      and were reluctant to associate potentially explained, non-specific or episodic
      symptoms with LC, even after diagnosis. CONCLUSIONS: Patients with early LC are
      unlikely to present symptoms possibly indicative of LC that they associate with
      normal processes, when attending primary care before diagnosis. Faced with
      patients at high LC risk, GPs will need to actively elicit potential LC symptoms
      not presented by the patient. Closed questions using non-disease terminology
      might better elicit normalised symptoms.

PMID- 23166139
TI  - Health literacy, health empowerment and health information search in the field of
      MMR vaccination: a cross-sectional study protocol.
AB  - OBJECTIVES: Although public health offices have a detailed record of the
      vaccination coverage among adolescents in Switzerland, little is known about the
      factors that determine the decisions of parents to get their children vaccinated.
      Based on Schulz & Nakamoto's Extended Health Empowerment Model, the present study
      aims at surveying parents of adolescents in Ticino (Switzerland) to get insights
      into the role of health literacy, health empowerment, information search
      behaviour and potential confounding variables that influence whether adolescents
      are not at all vaccinated, undervaccinated or fully covered against measles,
      mumps and rubella (MMR). METHODS AND ANALYSIS: A survey including concepts of the
      Extended Health Empowerment Model will be administered to all families with
      adolescents attending the third year of middle school in Ticino. Subsequently,
      survey responses will be matched with actual data on MMR vaccination coverage of
      adolescents collected from the Cantonal Office of Public Health in Ticino.
      DISCUSSION: The results of this study will allow one to draw more comprehensive
      conclusions about the factors that play a role in parents' decisions regarding
      the vaccination of their children. At the same time, the study will provide
      useful insights on which are the main issues to be considered when addressing
      parents (on an interpersonal as well as a mass communication level) regarding the
      vaccination of their children.

PMID- 23166138
TI  - 'Are decisions about discharge of elderly hospital patients mainly about freeing
      blocked beds?' A qualitative observational study.
AB  - OBJECTIVE: To explore the interactions concerning the frail and elderly patients
      having to do with discharge from acute hospital wards and their participation in
      medical decision-making. The views of the patients and the medical staff were
      both investigated. DESIGN: A qualitative observational and interview study using
      the grounded theory. SETTING AND PARTICIPANTS: The setting was three hospitals in
      rural and urban areas of two counties in Sweden of which one was a teaching
      hospital. The data comprised observations, healthcare staff interviews and
      patient interviews. The selected patients were all about to be informed that they
      were going to be discharged. RESULTS: The patients were seldom invited to
      participate in the decision-making regarding discharge. Generally, most
      communications regarding discharge were between the doctor and the nurse, after
      which the patient was simply informed about the decision. It was observed that
      the discharge information was often given in an indirect way as if other, albeit
      absent, people were responsible for the decision. Interviews with the healthcare
      staff revealed their preoccupation with the need to free up beds: 'thinking about
      discharge planning all the time' was the core category. This focus not only
      failed to fulfil the complex needs of elderly patients, it also generated
      feelings of frustration and guilt in the staff, and made the patients feel
      unwelcome. CONCLUSIONS: Frail elderly patients often did not participate in the
      medical decision-making regarding their discharge from hospital. The staff was
      highly focused on patients getting rapidly discharged, which made it difficult to
      fulfil the complex needs of these patients.

PMID- 23166140
TI  - The Treatment of cardiovascular Risk in Primary care using Electronic Decision
      supOrt (TORPEDO) study-intervention development and protocol for a cluster
      randomised, controlled trial of an electronic decision support and quality
      improvement intervention in Australian primary healthcare.
AB  - BACKGROUND: Large gaps exist in the implementation of guideline recommendations
      for cardiovascular disease (CVD) risk management. Electronic decision support
      (EDS) systems are promising interventions to close these gaps but few have
      undergone clinical trial evaluation in Australia. We have developed
      HealthTracker, a multifaceted EDS and quality improvement intervention to improve
      the management of CVD risk. METHODS/DESIGN: It is hypothesised that the use of
      HealthTracker over a 12-month period will result in: (1) an increased proportion
      of patients receiving guideline-indicated measurements of CVD risk factors and
      (2) an increased proportion of patients at high risk will receive guideline
      indicated prescriptions for lowering their CVD risk. Sixty health services (40
      general practices and 20 Aboriginal Community Controlled Health Services (ACCHSs)
      will be randomised in a 1:1 allocation to receive either the intervention package
      or continue with usual care, stratified by service type, size and participation
      in existing quality improvement initiatives. The intervention consists of point
      of-care decision support; a risk communication interface; a clinical audit tool
      to assess performance on CVD-related indicators; a quality improvement component
      comprising peer-ranked data feedback and support to develop strategies to improve
      performance. The control arm will continue with usual care without access to
      these intervention components. Quantitative data will be derived from cross
      sectional samples at baseline and end of study via automated data extraction.
      Detailed process and economic evaluations will also be conducted. ETHICS AND
      DISSEMINATION: The general practice component of the study is approved by the
      University of Sydney Human Research Ethics Committee (HREC) and the ACCHS
      component is approved by the Aboriginal Health and Medical Research Council HREC.
      Formal agreements with each of the participating sites have been signed. In
      addition to the usual scientific forums, results will be disseminated via
      newsletters, study websites, face-to-face feedback forums and workshops. TRIAL
      REGISTRATION: The trial is registered with the Australian Clinical Trials
      Registry ACTRN 12611000478910.

PMID- 23166141
TI  - Protocol for a randomised clinical study comparing the effect of Roux-en-Y
      gastric bypass and sleeve gastrectomy on reactive hypoglycaemia in morbidly obese
      subjects.
AB  - INTRODUCTION: Roux-en-Y gastric bypass (RYGB) is the most performed bariatric
      operation. Reactive hypoglycaemia is a frequent late complication occurring in
      about 72% of RYGB patients, which can present with various intensities up to the
      serious form of neuroglycopaenia. However, it seems to occur also after sleeve
      gastrectomy (SG) although much more rarely. METHODS AND ANALYSIS: A single
      centre, open, 1-year randomised trial to compare the incidence of hypoglycaemia
      after RYGB or SG. A secondary objective is the assessment of the comparative
      ability of the two surgical procedures in determining the improvement or
      normalisation of insulin sensitivity, given the established relevance of insulin
      resistance in the cardiometabolic syndrome of obesity. ETHICS AND DISSEMINATION:
      The study will be published and presented to international meetings and, due to
      the safety issue, it will represent a relevant information for national
      healthcare systems. The protocol was approved by the Catholic University Ethical
      Committee (A1534/CE/2012). Clinicaltrials.gov Registration n. NCT01581801.

PMID- 23166142
TI  - Moral sensitivity relating to the application of the code of ethics.
AB  - This study investigated the clinical application of the 2006 Third Revised Korean
      Nurses' Code of Ethics and the moral sensitivity of nurses. A total of 303
      clinical nurses in South Korea participated in the survey in May and June 2011.
      As instruments of this study, we used the 15 statements of the Korean Nurses'
      Code of Ethics and Korean Moral Sensitivity Questionnaire. The mean score for
      application was 3.77 +/- 0.59 (out of 5), and the mean score for moral
      sensitivity was 5.14 +/- 0.55 (out of 7). The correlation coefficient (r) of the
      application and moral sensitivity was 0.336 (p < 0.001). Nurses who scored high
      on moral sensitivity also scored high on application (t = -5.018, p < 0.001). In
      clinical settings, educational programmes to develop the moral sensitivity of
      nurses are necessary for improving the application of the code of ethics.

PMID- 23166143
TI  - Equality for followers of South Asian religions in end-of-life care.
AB  - Significant minority populations confer richness and diversity to British
      society. Responsive end-of-life care is a universal need that has ascended the
      public agenda following myriad reports of inadequate provision. Nevertheless, the
      potential exists for unwitting discrimination when caring for terminally ill
      patients on the basis of their religion or faith. Recent implementation of the
      Equality Act 2010, together with the government and professional initiatives,
      promises to positively impact upon this area of contemporary relevance and
      concern, although the extent to which facilitative policies can truly enhance
      patient care will depend upon how these are translated into care at the bedside.
      The contributions of health professionals will be central in meeting the
      challenges and seizing the opportunities for meeting the religion and faith
      interests of patients of South Asian descent.

PMID- 23166144
TI  - 'Working behind the scenes'. An ethical view of mental health nursing and first
      episode psychosis.
AB  - The aim of this study was to explore and reflect upon mental health nursing and
      first-episode psychosis. Seven multidisciplinary focus group interviews were
      conducted, and data analysis was influenced by a grounded theory approach. The
      core category was found to be a process named 'working behind the scenes'. It is
      presented along with three subcategories: 'keeping the patient in mind',
      'invisible care' and 'invisible network contact'. Findings are illuminated with
      the ethical principles of respect for autonomy and paternalism. Nursing care is
      dynamic, and clinical work moves along continuums between autonomy and
      paternalism and between ethical reflective and non-reflective practice. 'Working
      behind the scenes' is considered to be in a paternalistic area, containing an
      ethical reflection. Treating and caring for individuals experiencing first
      episode psychosis demands an ethical awareness and great vigilance by nurses. The
      study is a contribution to reflection upon everyday nursing practice, and the
      conclusion concerns the importance of making invisible work visible. 

PMID- 23166145
TI  - The importance of moral sensitivity when including persons with dementia in
      qualitative research.
AB  - The aim of this article is to show the importance of moral sensitivity when
      including persons with dementia in research. The article presents and discusses
      ethical challenges encountered when a total of 15 persons with dementia from two
      nursing homes and seven proxies were included in a qualitative study. The
      examples show that the ethical challenges may be unpredictable. As researchers,
      you participate with the informants in their daily life and in the interviews,
      and it is not possible to plan all that may happen during the research. A
      procedural proposal to an ethical committee at the beginning of a research
      project based on traditional research ethical principles may serve as a
      guideline, but it cannot solve all the ethical problems one faces during the
      research process. Our main argument in this article is, therefore, that moral
      sensitivity is required in addition to the traditional research ethical
      principles throughout the whole process of observing and interviewing the
      respondents.

PMID- 23166146
TI  - Professional values, self-esteem, and ethical confidence of baccalaureate nursing
      students.
AB  - Professional identity and competent ethical behaviors of nursing students are
      commonly developed through curricular inclusion of professional nursing values
      education. Despite the enactment of this approach, nursing students continue to
      express difficulty in managing ethical conflicts encountered in their practice.
      This descriptive correlational study explores the relationships between
      professional nursing values, self-esteem, and ethical decision making among
      senior baccalaureate nursing students. A convenience sample of 47 senior nursing
      students from the United States were surveyed for their level of internalized
      professional nursing values (Revised Professional Nursing Values Scale), level of
      self-esteem (Rosenberg's Self-Esteem Scale), and perceived level of confidence in
      ethical decision making. A significant positive relationship (p < 0.05) was found
      between nursing students' professional nursing values and levels of self-esteem.
      The results of this study can be useful to nursing educators whose efforts are
      focused on promoting professional identity development and competent ethical
      behaviors of future nurses.

PMID- 23166147
TI  - Long-term quality of sleep after remifentanil-based anaesthesia: a randomized
      controlled trial.
AB  - BACKGROUND: Clinical and pre-clinical data agree that opioids disrupt sleep
      architecture. Recently, remifentanil has been suggested to cause possible long
      term disturbances of sleep quality. This randomized controlled clinical trial was
      designed to substantiate or refute a possible long-term effect of remifentanil on
      the quality of sleep. METHODS: One hundred patients undergoing elective surgery
      were randomized to receive either fentanyl or remifentanil-based anaesthesia.
      Before operation (T0) and 3 (T3) and 6 (T6) months after operation, the quality
      of sleep was assessed by the Pittsburgh Sleep Quality Index (PSQI). RESULTS:
      Overall, the quality of sleep for patients in the remifentanil or fentanyl group
      was not significantly different at any time point. Patients in the fentanyl group
      screened as good sleepers before operation showed no differences across time
      course of the study in PSQI scores. In contrast, good sleepers in the
      remifentanil group had significantly impaired sleep quality for at least 3 months
      after operation. Patients who were before operation screened as poor sleepers
      showed no significant changes in PSQI scores at T3 and T6 in both groups.
      CONCLUSIONS: The intraoperative use of remifentanil in a general patient
      population does not significantly alter the quality of sleep in the postoperative
      period. However, it may result in a significant reduction in the quality of sleep
      in patients before operation considered good sleepers. These changes were not
      observed in the group of patients receiving fentanyl. The relevance of these
      findings in terms of patient recovery and quality-of-life warrants further
      investigation. Trial Registration. ACTRN12610000362099.

PMID- 23166148
TI  - Influence of drugs on the response characteristics of the LiDCO sensor: an in
      vitro study.
AB  - BACKGROUND: In a previous study, the authors found a large bias (50%) for lithium
      (LiDCO) compared with thermodilution cardiac output measurement methods in ponies
      receiving i.v. infusions of xylazine, ketamine, and midazolam. This prompted the
      authors to examine the effect of drugs on the LiDCO sensor. METHODS: Drugs and
      lithium were dissolved in 0.9% saline to produce the following solutions: saline,
      saline-lithium, saline-drug, and saline-drug-lithium. The drug concentrations
      were overlapping the range of clinical interest as estimated from the published
      literature. These 38 degrees C solutions were pumped through the LiDCO sensor in
      predetermined order. Sensor voltages were measured. Differences between lithium
      induced voltage changes in the absence and presence of drugs indicated erroneous
      lithium detections that, if they occurred in vivo, may cause biases in LiDCO
      measurements. RESULTS: Clonidine, detomidine, dexmedetomidine, medetomidine,
      romifidine, xylazine, ketamine, S-ketamine, lidocaine, and rocuronium caused
      concentration-dependent increases in sensor voltages and negative biases in
      lithium detection that were mathematically equivalent to greater than +10% biases
      in LiDCO. The drug-induced voltage changes correlated with calculated biases in
      LiDCO (r(2)=0.91). Atipamezole, acepromazine, butorphanol, diazepam, midazolam,
      and guaifenesin caused minimal or no interaction in this study. CONCLUSIONS: A
      number of drugs influenced the accuracy of the LiDCO sensor in vitro but, based
      on published pharmacokinetic data, only xylazine, ketamine, lidocaine, and
      rocuronium may cause biases at clinically relevant concentrations. These findings
      need to be confirmed in vivo. Relevant (>3 mV) changes in sensor voltages due to
      the presence of drugs may indicate possible interactions with the LiDCO sensor.

PMID- 23166149
TI  - Bispectral index-guided induction of general anaesthesia in patients undergoing
      major abdominal surgery using propofol or etomidate: a double-blind, randomized,
      clinical trial.
AB  - BACKGROUND: In a double-blind, randomized trial, we compared the haemodynamic
      effects of a bispectral index (BIS)-guided etomidate and propofol infusion for
      anaesthesia induction in patients undergoing major abdominal surgery. METHODS:
      Forty-six patients were randomly assigned to two groups based on the induction of
      anaesthesia, performed with a BIS value of 60 titrated infusion of etomidate (E
      group) or propofol (P group). Mean arterial pressure (MAP), cardiac index (CI),
      heart rate, and systemic vascular resistance index (SVRI) measurements were taken
      1 min before induction and recorded at 1-min intervals for 20 min. P<0.05 was
      considered statistically significant. RESULTS: Before intubation, no significant
      differences between the two groups regarding the haemodynamics were noticed. At
      intubation and up to 7 min after intubation MAP (P=0.019) was significantly
      higher in the E group. CI was significantly higher in the E group with respect to
      the P group 2, 6, and 7 min after intubation. Twenty-three patients developed
      complications. The incidence of hypotension was higher in the P group than that
      in the E group (8 vs 3; P=0.08), and the incidence of hypertension was
      significantly higher in the E group than that in the P group (10 vs 2; P=0.007).
      CONCLUSIONS: Our study showed that the use of propofol resulted in less
      hypertension and tachycardia at and after intubation than etomidate. But even
      with the reduced doses given with the BIS-guided protocol, it often caused
      significant hypotension.

PMID- 23166150
TI  - Molecular subclasses of breast cancer: how do we define them? The IMPAKT 2012
      Working Group Statement.
AB  - The 2012 IMPAKT task force investigated the medical usefulness of current methods
      for the classification of breast cancer into the 'intrinsic' molecular subtypes
      (luminal A, luminal B, basal-like and HER2). A panel of breast cancer and/or gene
      expression profiling experts evaluated the analytical validity, clinical validity
      and clinical utility of two approaches for molecular subtyping of breast cancer:
      the prediction analysis of microarray (PAM)50 assay and an immuno-histochemical
      (IHC) surrogate panel including oestrogen receptor (ER), HER2 and Ki67. The panel
      found the currently available evidence on the analytical validity and clinical
      utility of Ki67 based on a 14% cut-off and PAM50 to be inadequate. The majority
      of the working group members found the available evidence on the analytical
      validity, clinical validity and clinical utility of ER/HER2 to be convincing. The
      panel concluded that breast cancer classification into molecular subtypes based
      on the IHC assessment of ER, HER2 and Ki67 with a 14% cut-off and on the PAM50
      test does not provide sufficiently robust information to modify systemic
      treatment decisions, and recommended the use IHC for ER and HER2 for the
      identification of clinically relevant subtypes of breast cancers. Methods for
      breast cancer classification into molecular subtypes should, however, be
      incorporated into clinical trial design.

PMID- 23166152
TI  - Empowerment and bariatric surgery: negotiations of credibility and control.
AB  - Today obesity is understood as a chronic illness. Programs developed to deal with
      obesity often build on an explicit aim to "empower" patients to take increased
      responsibility for their health, in line with contemporary neoliberal discourses.
      There is little empirically based knowledge about this so-called empowering
      process. In this article we focus on how an empowering program for patients
      diagnosed as morbidly obese worked on individuals' identity. The program
      encompassed a course in lifestyle change, bariatric surgery, and aftercare. We
      conducted qualitative interviews with 9 individuals at different stages of their
      treatment process and applied discourse analysis to interpret their constructions
      and negotiations as they progressed through the program. We found that dimensions
      of control and credibility framed the respondents' identity work. Based on the
      findings we suggest that contemporary discourses of empowerment as practice might
      leave the participants "trapped" within the ambivalence of freedom and control.

PMID- 23166153
TI  - Desired mental health resources for urban, ethnically diverse, impoverished women
      struggling with anxiety and depression.
AB  - Depression and anxiety are mental health issues that disproportionately affect
      women-particularly when access to culturally sensitive care is limited. The
      purpose of this study was to identify mental health concerns in three urban,
      ethnically diverse, underserved, and impoverished neighborhoods using the
      ideological perspective of community-based participatory research. In the context
      of long-term partnerships between a department of nursing and these
      neighborhoods, we recruited 61 women aged 18 to 69 years and collected data via
      homogeneous focus groups comprised of Black, Hispanic, and White women,
      respectively. We conducted five of the focus groups in English and one in
      Spanish. The women perceived anxiety and depression as significant concerns for
      themselves, their families, and their communities. They used unique community
      resources to manage mental health issues and desired new resources, including
      support groups and education.

PMID- 23166154
TI  - The entrepreneurial rationalities of governing and the construction of the
      enterprising nurse.
AB  - Drawing from a wider study exploring the role of registered nurses (RNs) in
      managing hospital care of older people, I present an analysis of some discursive
      mechanisms through which an enterprising nursing subjectivity was cultivated in
      RNs working in an Australian hospital. Data comprised information from the
      hospital Web site, policy documents, job descriptions, and interviews with 26
      RNs. The analysis highlighted how texts such as nursing vision statements and job
      descriptions were not neutral or innocuous, but mechanisms that individually and
      collectively specified norms of enterprising conduct for RNs working in that
      hospital. Although the findings detailed how entrepreneurial rationalities and
      discourses governing health care actively transformed the meaning and practice of
      nursing, they also illustrated how factors such as role location and ward culture
      diluted the take up of enterprise discourses, suggesting that it was not possible
      to guarantee RNs as particular kinds of enterprising subjects.

PMID- 23166151
TI  - The initial hours of metastasis: the importance of cooperative host-tumor cell
      interactions during hematogenous dissemination.
AB  - Tumor cells transit from the primary tumor via the blood circulation to form
      metastases in distant organs. During this process, tumor cells encounter a number
      of environmental challenges and stimuli that profoundly impact their metastatic
      potential. Here, we review the cooperative and dynamic host-tumor cell
      interactions that support and promote the hematogenous dissemination of cancer
      cells to sites of distant metastasis. In particular, we discuss what is known
      about the cross-talk occurring among tumor cells, platelets, leukocytes, and
      endothelial cells and how these cell-cell interactions are organized both
      temporally and spatially at sites of extravasation and in the early metastatic
      niche. SIGNIFICANCE: Metastasis is a function not only of tumor cells but also
      involves cooperative interactions of those cells with normal cells of the body,
      in particular platelets and leukocytes. These other cell types alter the behavior
      of the tumor cells themselves and of endothelial cells lining the vasculature and
      assist in tumor cell arrest and extravasation at sites of metastasis and
      subsequently in the establishment of tumor cells in the early metastatic niche. A
      better understanding of the important role that these contact and paracrine
      interactions play during metastasis will offer new opportunities for therapeutic
      intervention.

PMID- 23166155
TI  - Maps, models, and narratives: the ways people talk about depression.
AB  - Many researchers within the social sciences, medicine, and humanities have
      examined the ways people talk and think about depression. In their research and
      published literature they have attempted to determine the theoretical frameworks
      and appropriate language for categorizing such concepts and understandings.
      Drawing from mental health and broader social science scholarship, in this
      article we examine three approaches to developing an inclusive understanding of
      depression experiences: explanatory models, exploratory maps, and illness
      narratives. Utilizing these terms in the analysis of a single dataset, we
      identified multiple conceptual terms with potential analytical validity.
      Furthermore, we argue that variable usage and meanings of these concepts among
      lay people might contribute to a shared understanding of depression between lay
      people and experts, and ultimately have positive consequences for clinical
      practice.

PMID- 23166156
TI  - Desperately seeking dissonance: identifying the disconfirming case in qualitative
      evidence synthesis.
AB  - Actively seeking the disconfirming or deviant case is properly regarded as a
      hallmark of trustworthiness in primary qualitative research. The need to subject
      emergent theory to such testing is no less important within qualitative
      systematic reviews. There is, as yet, little available guidance on how to
      implement such strategies. Few researchers have described the practicalities of
      seeking the disconfirming case. We survey the methodological literature to gain a
      better understanding of how systematic reviews of qualitative research handle the
      disconfirming case. We reflect on our own experience from three recent
      qualitative evidence syntheses. We describe how reviewers might actively
      manufacture opportunities to identify discrepant or refutational findings. We
      conclude by outlining possible methods by which a team might integrate active
      seeking of a disconfirming case within the overall review process.

PMID- 23166157
TI  - Madeleine M. Leininger, 1925-2012.

PMID- 23166158
TI  - Fare well, Human Reproduction.

PMID- 23166159
TI  - A comparison of incomplete-data methods for categorical data.
AB  - We studied four methods for handling incomplete categorical data in statistical
      modeling: (1) maximum likelihood estimation of the statistical model with
      incomplete data, (2) multiple imputation using a loglinear model, (3) multiple
      imputation using a latent class model, (4) and multivariate imputation by chained
      equations. Each method has advantages and disadvantages, and it is unknown which
      method should be recommended to practitioners. We reviewed the merits of each
      method and investigated their effect on the bias and stability of parameter
      estimates and bias of the standard errors. We found that multiple imputation
      using a latent class model with many latent classes was the most promising method
      for handling incomplete categorical data, especially when the number of variables
      used in the imputation model is large.

PMID- 23166160
TI  - Maximum likelihood estimation of time to first event in the presence of data gaps
      and multiple events.
AB  - We propose a novel likelihood method for analyzing time-to-event data when
      multiple events and multiple missing data intervals are possible prior to the
      first observed event for a given subject. This research is motivated by data
      obtained from a heart monitor used to track the recovery process of subjects
      experiencing an acute myocardial infarction. The time to first recovery, T1, is
      defined as the time when the ST-segment deviation first falls below 50% of the
      previous peak level. Estimation of T1 is complicated by data gaps during
      monitoring and the possibility that subjects can experience more than one
      recovery. If gaps occur prior to the first observed event, T, the first observed
      recovery may not be the subject's first recovery. We propose a parametric gap
      likelihood function conditional on the gap locations to estimate T1 Standard
      failure time methods that do not fully utilize the data are compared to the gap
      likelihood method by analyzing data from an actual study and by simulation. The
      proposed gap likelihood method is shown to be more efficient and less biased than
      interval censoring and more efficient than right censoring if data gaps occur
      early in the monitoring process or are short in duration.

PMID- 23166161
TI  - TRIF mediates Toll-like receptor 2-dependent inflammatory responses to Borrelia
      burgdorferi.
AB  - TRIF is an adaptor molecule important in transducing signals from intracellularly
      signaling Toll-like receptor 3 (TLR3) and TLR4. Recently, TLR2 was found to
      signal from intracellular compartments. Using a synthetic ligand for TLR2/1
      heterodimers, as well as Borrelia burgdorferi, which is a strong activator of
      TLR2/1, we found that TLR2 signaling can utilize TRIF. Unlike TRIF signaling by
      other TLRs, TLR2-mediated TRIF signaling is dependent on the presence of another
      adaptor molecule, MyD88. However, unlike MyD88 deficiency, TRIF deficiency does
      not result in diminished control of infection with B. burgdorferi in a murine
      model of disease. This appears to be due to the effects of MyD88 on phagocytosis
      via scavenger receptors, such as MARCO, which are not affected by the loss of
      TRIF. In mice, TRIF deficiency did have an effect on the production of
      inflammatory cytokines, suggesting that regulation of inflammatory cytokines and
      control of bacterial growth may be uncoupled, in part through transduction of
      TLR2 signaling through TRIF.

PMID- 23166162
TI  - RNA interference-mediated silencing of Atp6i prevents both periapical bone
      erosion and inflammation in the mouse model of endodontic disease.
AB  - Dental caries is one of the most prevalent infectious diseases in the United
      States, affecting approximately 80% of children and the majority of adults.
      Dental caries may lead to endodontic disease, where the bacterial infection
      progresses to the root canal system of the tooth, leading to periapical
      inflammation, bone erosion, severe pain, and tooth loss. Periapical inflammation
      may also exacerbate inflammation in other parts of the body. Although
      conventional clinical therapies for this disease are successful in approximately
      80% of cases, there is still an urgent need for increased efficacy of treatment.
      In this study, we applied a novel gene-therapeutic approach using recombinant
      adeno-associated virus (AAV)-mediated Atp6i RNA interference (RNAi) knockdown of
      Atp6i/TIRC7 gene expression to simultaneously target periapical bone resorption
      and periapical inflammation. We found that Atp6i inhibition impaired osteoclast
      function in vitro and in vivo and decreased the number of T cells in the
      periapical lesion. Notably, AAV-mediated Atp6i/TIRC7 knockdown gene therapy
      reduced bacterial infection-stimulated bone resorption by 80% in the mouse model
      of endodontic disease. Importantly, Atp6i(+/-) mice with haploinsufficiency of
      Atp6i exhibited protection similar to that in mice with bacterial infection
      stimulated bone erosion and periapical inflammation, which confirms the potential
      therapeutic effect of AAV-small hairpin RNA (shRNA)-Atp6i/TIRC7. Our results
      demonstrate that AAV-mediated Atp6i/TIRC7 knockdown in periapical tissues can
      inhibit endodontic disease development, bone resorption, and inflammation,
      indicating for the first time that this potential gene therapy may significantly
      improve the health of those who suffer from endodontic disease.

PMID- 23166163
TI  - Adult-onset Still's disease revealed by perimyocarditis and a concomitant
      reactivation of an EBV infection.
AB  - We describe a 17-year-old patient presenting perimyocarditis as the initial
      manifestation of the adult-onset Still's disease. Corticotherapy was rapidly
      successful but induced major acute hepatitis in relation with Epstein-Barr virus
      reactivation. After 1 year, even if the global outcome is favourable, a slightly
      lowered ejection fraction still persists. Former case reports and differential
      diagnosis with reactive haemophagocytic syndrome would be discussed.

PMID- 23166164
TI  - A fatal mongoose bite.
AB  - Animal bite is a bite wound from a pet, farm or wild animal. Dog bites make up 80
      85% of all reported incidents. Cats amount for about 10% of reported bites and
      other animals such as rodents, rabbits, horses, raccoons, bats and monkeys amount
      to 5-10%. Bites by mongoose are uncommon. Here, we present a case of fatal
      mongoose bite to an elderly woman who died as a complication of streptococcal
      infection at the bite site.

PMID- 23166165
TI  - Uncommon presentation of a common cancer papillary thyroid cancer in paediatric
      population.
AB  - Carcinoma of thyroid gland is rare in the paediatric age group before the age of
      15 years. A 12-year-old girl presented with a swelling in the midline of neck,
      with no exposure of radiation in the past. On ultrasonography and fine needle
      aspiration cytology, the findings were suggestive of papillary carcinoma of
      thyroid. The case is being reported on account of its rarity.

PMID- 23166166
TI  - Heterotopic pregnancy: should we instrument the uterus at laparoscopy for ectopic
      pregnancy.
AB  - The coexistence of intrauterine and ectopic pregnancy (heterotopic pregnancy)
      occurs in 1/30,000 of spontaneous pregnancies. However, it is getting more common
      at 1/900 in clomiphene citrate-induced pregnancies and rises to 1% in assisted
      reproduction. It is a potentially life-threatening condition with diagnostic and
      therapeutic complexities. Our patient is a 40-year-old who has been trying to get
      pregnant for 3 years. A planned non-instrumentation of the uterus at laparoscopy
      despite clear signs of a ruptured ectopic pregnancy has given her a chance of a
      continuing intrauterine pregnancy. With the increasing number of in vitro
      fertilisation-embryo transfers, the incidence of heterotopic pregnancies is also
      increasing, hence issues discussed here is whether the uterus should be
      instrumented at all during laparoscopy in early pregnancy and misdiagnosis with
      its sequel.

PMID- 23166167
TI  - An unusual method of diagnosing a common disease.
AB  - A 34-year-old woman presented with non-bloody diarrhoea of 14 days duration and
      vomiting. Physical examination was unremarkable. She had hypokalaemia and
      metabolic acidosis. Stool studies were negative for Clostridium difficile toxin,
      faecal leucocytes and parasites. Colon appeared normal on colonoscopy. Pronounced
      scalloping of ileal folds was noted on ileoscopy. Ileal biopsies revealed villous
      blunting, crypt hyperplasia, marked intraepithelial lymphocytosis and lymphocytic
      infiltration of the lamina propria, consistent with lymphocytic ileitis in
      coeliac disease. Serology revealed elevated antitissue transglutaminase IgA
      antibodies (>100 U/ml). Institution of a strict gluten free diet resulted in
      complete resolution of symptoms. Although rare, coeliac disease can present as an
      acute diarrhoeal illness and should be considered after infectious aetiologies
      are excluded.

PMID- 23166168
TI  - TURP syndrome and severe hyponatremia under general anaesthesia.
AB  - Transurethral resection of prostate (TURP) syndrome is a complication
      characterised by symptoms changing from an asymptomatic hyponatremic state to
      convulsions, coma and death due to absorption of irrigation fluid during TURP.
      The syndrome appears to be related to the amount of fluid that enters the
      circulation via the blood vessels in the resection area. The first step in the
      course of action for therapy is to control bleeding and suspend the operation. In
      the case presented, we aimed to emphasise the importance of an early diagnosis
      and treatment of TURP syndrome in a patient that developed hyponatremia (90
      mmol/l) while under general anaesthesia during a TURP procedure. In addition,
      multiple cystoscopic applications in the same session may facilitate development
      of the TURP syndrome.

PMID- 23166170
TI  - An unusual presentation of cholecystoduodenal fistula: vomiting of gallstones.
AB  - Bouveret's syndrome is defined as gastric outlet obstruction secondary to an
      impacted gallstone in the duodenum via a cholecystoduodenal or cholecystogastric
      fistula. Common radiological findings include pneumobilia, calcified right upper
      quadrant mass, pyloric or duodenal obstruction and cholecystoduodenal fistula.
      Initial attempts through endoscopic retrieval may be successful; however, results
      can vary. Surgical options include enterolithotomy or gastrotomy with or without
      cholecystectomy and fistula repair. We describe a unique case of Bouveret's
      syndrome with short-lived obstruction followed by vomiting of gallstones in a
      morbidly obese patient and discuss the complexities of investigation and
      management of these patients.

PMID- 23166169
TI  - Juvenile cystic adenomyoma.
AB  - The purpose of this paper is to describe a case of juvenile cystic adenomyoma in
      a 17 year-old female patient with severe dysmenorrhoea unresponsive to non
      steroidal anti-inflammatory drugs. The patient presents progressively worsening
      dysmenorrhoea that started 2 years after menarche and a cystic uterine lesion in
      MRI. The cyclic nature of symptoms, the similarity of the lesion and endometrium
      in MRI signal intensity and response to hormone suppression are consistent with
      juvenile cystic adenomyoma. The treatment depends on the age of the patient,
      severity of her symptoms and size and localisation of the cyst. This is a rare
      condition in young nulliparous women with a challenging differential diagnosis.
      This case highlights the relevance of MRI in the patient's study, featuring
      important characteristics of the lesion that disclosed the final diagnosis.

PMID- 23166171
TI  - A delayed diagnosis of a retained guidewire during central venous
      catheterisation: a case report and review of the literature.
AB  - Central venous catheterisation allows delivery of medications, intravenous
      fluids, parenteral nutrition, haemodialysis and monitoring of haemodynamic
      variables. Various complications may occur during and after the procedure.
      However, the complete guidewire retention has rarely been reported. In this
      report, we have presented a complete guidewire retention as a result of
      inadvertent catheter insertion. After 17 months of the first operation performed
      upon the diagnosis of Fournier's gangrene, the patient was admitted to the
      cardiology polyclinic with a recurrent chest pain. Echocardiography showed a wire
      shaped foreign body within the right part of the heart, and a fluoroscopic
      examination showed a guidewire reaching from the superior vena cava to the right
      external iliac vein. In retrospect, the wire was already visible on the
      postoperative chest x-rays and CT taken while the patient was still in intensive
      care unit, but its presence was overlooked at that time. The guidewire was
      retrieved completely during a surgery.

PMID- 23166172
TI  - Large ameloblastic fibro-odontoma in an 18-year-old girl and review of
      literature.
AB  - The ameloblastic fibro-odontoma is a rare, benign, mixed neoplasm composed of
      proliferating odontogenic epithelium, ectomesenchymal tissue and varying degrees
      of dental hard tissue formation. It occurs exclusively as an intraosseous lesion.
      It usually exhibits slow growth and is commonly seen in children and young
      adults. Radiologically, ameloblastic fibro-odontoma appears as a circumscribed
      radiolucency which may contain radiopaque foci. Most cases of ameloblastic fibro
      odontoma exhibit benign behaviour, but cases of malignant transformation have
      been reported. The treatment modality in most cases involves conservative
      surgery, but in cases with malignant transformation more radical treatment will
      be required. A massive ameloblastic fibro-odontoma involving the mandible is
      being described here with its clinical, radiological and histopathological
      features.

PMID- 23166173
TI  - Fungal myocarditis in a preterm neonate.
AB  - A male infant born at 25 weeks gestation presented with abdominal distension, was
      transferred to our institution for surgical management following suspected bowel
      perforation with severe sepsis. Umbilical catheter cultures grew Candida
      parapsilosis. At laparotomy, there was a large ileal perforation with
      peritonitis, he was treated with amphotericin, antibiotics and had an ileostomy.
      He had persistent pulmonary hypertension, requiring nitric oxide and high
      frequency oscillatory ventilation. Serial echocardiograms revealed a patent
      ductus arteriosus (PDA), but also demonstrated increasing left ventricular
      hypertrophy and the development of bright areas within the septal myocardium.
      Further bright areas developed over a course of 2 weeks in his right ventricular
      outflow tract. After treatment for candidal infection, there was improvement in
      left ventricular thickness and brightness of the echogenic lesions was reduced.
      Biopsy of the lesions was discounted due to the risk of the procedure, the size
      of the infant and his improving clinical status.

PMID- 23166174
TI  - Occlusion of the artery of Percheron: an unusual cause of bilateral stroke.
AB  - The artery of Percheron is a rare anatomical variant whereby a single vessel
      arising from the proximal segment of one posterior cerebral artery supplies both
      medial thalami. This is a rare example of a single arterial supply to brain
      structures on both sides of the midline. Occlusion of the artery of Percheron
      results in bilateral medial thalamic infarction, which is manifest clinically as
      gaze paresis, cognitive disturbance and altered consciousness. The presentation
      can mimic subarachnoid haemorrhage, drug intoxication, encephalitis and other
      inflammatory or infective conditions. The presentation is similar to the 'top of
      the basilar syndrome' and early recognition should prompt further investigation
      for underlying stroke aetiologies and consideration can be given to thrombolysis
      if vascular occlusion can be confirmed.

PMID- 23166175
TI  - Temporal arteritis presenting with tongue necrosis.
AB  - Spontaneous glossodynia is uncommon and glossodynia progressing to necrosis is
      especially rare. Although the commonest cause of lingual necrosis is giant cell
      arteritis, only a few cases of a new diagnosis of giant cell arteritis,
      clinically presenting with isolated lingual necrosis, have been reported.

PMID- 23166176
TI  - Hypertension, secondary to a renal artery aneurysm, treated by ex vivo aneurysm
      repair and autotransplantation.
AB  - Hypertension is becoming a more common problem in childhood and adolescence.
      About 5-10% of paediatric patients with hypertension have underlying renovascular
      disease. Although renal artery aneurysms (RAAs) are an uncommon cause of disease
      of the renal vessels, they are recognised as a cause of hypertension. We describe
      a 15-year-old man with symptomatic hypertension who after extensive investigation
      was found to have a right RAA. Our patient responded to conservative management
      with two antihypertensive agents, but as a young sports enthusiast, he was keen
      to pursue more definitive options. Complex anatomy of the aneurysm precluded the
      use of endovascular treatment. Surgical options were explored, and after
      counselling, our patient underwent a nephrectomy, ex vivo aneurysm repair and
      autotransplantation with which his hypertension resolved. Our case highlights the
      difficulty of diagnosing RAAs in hypertensive patients and that, in carefully
      selected patients, invasive surgical intervention of RAAs is a viable treatment
      option.

PMID- 23166177
TI  - Diagnostic use of MRI in the non-mobile infant.

PMID- 23166178
TI  - Syndrome of inappropriate antidiuresis in doxylamine overdose.
AB  - Doxylamine succinate, an H(1)-antihistamine drug, is commonly used as sleep
      inducing agent as well as therapy for nausea and vomiting in pregnancy. At usual
      doses, it may cause impairment of cognitive and psychomotor performance,
      anticholinergic effects, agitation and postural hypotension. Besides, since this
      drug is frequently involved in either accidental or intentional overdoses, it
      seems relevant to bear in mind other possible toxic effects. We report a case of
      acute severe hyponatremia in the setting of a syndrome of inappropriate
      antidiuresis (SIAD), an apparent new adverse effect linked to doxylamine
      overdose. The Naranjo adverse drug reaction probability scale indicated a
      probable relationship between doxylamine intake and SIAD development. SIAD may be
      considered as a potential, serious adverse reaction of doxylamine overdose.
      Clinicians should consider this aetiological possibility when attending patients
      suffering from hyponatremia.

PMID- 23166179
TI  - Occlusion of a clival dural arteriovenous fistula using a novel approach through
      the foramen ovale.
AB  - Dural arteriovenous fistulas (DAVFs) are abnormal connections between arteries
      and veins that are classified by location, morphology or direction of venous
      drainage. Treatment of DAVFs is undertaken in patients with severe symptoms or
      those with retrograde cortical venous drainage and/or venous ectasia. Much is
      written regarding the treatment of DAVFs involving the transverse sigmoid
      sinuses, cavernous sinus and tentorium, but little is written concerning the
      treatment of clival DAVFs. We demonstrate a novel transforaminal percutaneous
      approach through the foramen ovale as a viable method to occlude a clival vein.
      Specialised software was used to create a safe trajectory to the DAVF via the
      foramen ovale. The patient then underwent successful occlusion of the clival
      DAVF, thus further increasing the neurointerventionalist's armamentarium when
      attempting to treat difficult to reach clival DAVFs.

PMID- 23166180
TI  - Value of histopathology, immunohistochemistry, and real-time polymerase chain
      reaction in the confirmatory diagnosis of Encephalitozoon cuniculi infection in
      rabbits.
AB  - Morphological lesions in kidneys and brain are all too often considered
      diagnostic for confirmation of encephalitozoonosis in rabbits. The current study
      evaluated the diagnostic value of histology versus other etiological tests,
      including immunohistochemistry and real-time polymerase chain reaction (PCR) for
      Encephalitozoon cuniculi infection diagnosis. Samples of brain, heart, lungs,
      intestine, liver, and kidneys from 81 rabbits were examined for morphological
      lesions attributed to E. cuniculi infection as well as for the presence of spores
      and E. cuniculi antigen. Of these, 55 rabbits were tested for E. cuniculi DNA.
      Histological changes consistent with E. cuniculi infection were seen in 33
      rabbits (41%, 33/81) representing 87% (33/38) of all rabbits with confirmed E.
      cuniculi infection. Brains of these rabbits displayed 6 different types of focal
      lesions corresponding to the stage of infection and specific tissue response. In
      5 rabbits that were tested positive, histology was either inconclusive or
      inconspicuous. Etiological diagnosis was based on histological spore detection in
      16% (6/38) of infected rabbits. Immunohistochemistry was more sensitive (42%,
      16/38) than histological spore detection, and real-time PCR proved to be the most
      sensitive of all investigated methods (30/35, 86% of the examined rabbits with E.
      cuniculi infection). Encephalitozoon cuniculi infection rarely occurs without
      characteristic kidney and brain lesions. However, the spectrum of brain changes
      is wider than previously reported. Based on these findings, confirmation of
      pathogenic E. cuniculi infection should include standard histology of the
      predilection sites and a specific etiological assay, preferably real-time PCR.

PMID- 23166181
TI  - Comparison of fecal DNA extraction kits for the detection of Mycobacterium avium
      subsp. paratuberculosis by polymerase chain reaction.
AB  - Culture of Mycobacterium avium subsp. paratuberculosis (MAP) from feces has been
      considered the gold standard for the diagnosis of paratuberculosis for many
      years. However, direct fecal polymerase chain reaction (PCR) is becoming more
      widely used, demonstrating similar sensitivity and specificity to culture. To
      ensure efficient and reproducible PCR results from a difficult sample matrix such
      as feces, there are many obstacles that a DNA extraction method must overcome,
      including the presence of inhibitors and the thick waxy cell wall of MAP. In the
      current study, 6 commercial DNA extraction kits were evaluated using fecal
      samples from naturally infected cattle shedding various amounts of MAP. Upon
      extraction, DNA purity and yield were measured, and real-time PCR was performed
      for detection of the insertion sequence (IS)900 and ISMAP02 targets. The kits
      evaluated showed significant differences in the purity and yield of DNA obtained.
      The best results were observed with kits E and A, having identified 94% (16/17)
      and 76% (13/17) of the positive samples by IS900 PCR, respectively. Both of these
      kits utilized bead beating in a lysis solution for cell disruption, followed by
      spin column technology (kit E) or magnetic bead-based technology (kit A) for
      nucleic acid isolation and purification. Two kits (A and F) demonstrated improved
      performance when used in conjunction with the respective manufacturer's PCR test.
      The present study demonstrates the importance of choosing the correct methodology
      for the most accurate diagnosis of paratuberculosis through fecal PCR.

PMID- 23166182
TI  - Myocardial fibrosis associated with previous ingestion of yew (Taxus sp.) in a
      Holstein heifer: evidence for chronic yew toxicity in cattle.
AB  - Twenty-six 5-month-old Holstein calves were accidentally exposed to discarded
      branches of yew bushes (Taxus sp.). Several calves were found dead approximately
      24 hr after exposure; however, a few calves died several days after exposure. One
      calf died 18 days after the initial exposure to Taxus sp. and was examined on the
      farm via necropsy. Gross lesions included ascites, and dilated and flaccid
      myocardial ventricles. Sections of formalin-fixed heart were submitted to the
      Indiana Animal Disease Diagnostic Laboratory for histopathologic examination;
      fresh rumen contents were submitted for toxicologic testing. Histologically,
      large areas of myocardium were replaced by fibrous connective tissue, suggesting
      previous myocardial necrosis. Taxus alkaloids were identified in the rumen
      contents using gas chromatography-mass spectrometry. Based on the clinical
      history, the gross and histologic lesions, the identification of Taxus alkaloids
      in the rumen contents, and lack of exposure to other known cardiotoxic agents,
      yew toxicity was considered the cause of death in this calf. Ingestion of taxines
      is known to cause acute and subacute toxicity in human beings and animals;
      however, a chronic clinical course and severe histologic lesions have not been
      previously associated with yew toxicity. Although only 1 calf was examined, this
      case suggests that yew toxicity can result in a prolonged clinical course in
      cattle and can cause histologic myocardial lesions.

PMID- 23166183
TI  - Leishmania amastigotes in the central nervous system of a naturally infected dog.
AB  - A 4-year-old male Labrador Retriever dog was presented with a 10-day history of
      tetraplegia, depression, and absent postural reflexes. The cerebrospinal fluid
      was positive for Leishmania spp. DNA. At necropsy, a 2-cm long mass was observed
      adhered to C(7) and C(8) left spinal nerves. Microscopically, nerve fiber
      destruction together with mixed inflammatory infiltration was observed in the
      spinal nerves. Cervical spinal cord sections showed multifocal, diffuse
      granulomatous inflammation in the white matter. In the brain, perivascular
      infiltrates were observed in some areas together with subtle pallor of the
      parenchyma. Immunohistochemistry for Leishmania infantum confirmed the presence
      of amastigotes in the spinal nerves, spinal cord, brain parenchyma, and choroid
      plexuses. The current study describes the presence of Leishmania amastigotes in
      nervous tissue inciting radiculoneuritis, myelitis, and mild meningoencephalitis,
      suggesting a likely route by which L. infantum amastigotes reach and affect the
      central nervous system parenchyma.

PMID- 23166184
TI  - A case of umbilical cord teratoma in an aborted foal.
AB  - A 16-year-old primiparous mare aborted an apparently normal fetus at 240 days of
      gestation. A large, oval mass, measuring approximately 20 cm * 30 cm * 20 cm, was
      detected attached to the umbilical cord of the fetus. On the cut surface, the
      mass showed multifocal cystic structures, foci of mineralization, and diffuse
      hemorrhages. Histological examination of the mass revealed haphazardly arranged
      cartilage, bone, mesenchymal stroma, adipose tissue, vascular structures, smooth
      muscle, ciliated epithelium, squamous cornifying epithelium, and undifferentiated
      germ cells with areas of necrosis and mineralization. The mass was diagnosed as
      an umbilical cord teratoma, which is an extremely rare tumor in human beings and,
      to the authors' knowledge, has only described in the veterinary literature on one
      occasion.

PMID- 23166185
TI  - Retrospective swine influenza serological surveillance in the four highest pig
      density provinces of Thailand before the introduction of the 2009 pandemic
      Influenza A virus subtype H1N1 using various antibody detection assays.
AB  - Genetic characterization of the hemagglutinin gene of the 6 selected Thai Swine
      influenza virus (SIV) isolates (4 H1 and 2 H3 isolates) used in the establishment
      of a hemagglutination inhibition (HI) assay was analyzed. Based on the
      phylogenetic analysis, Thai SIVs could be divided into 3 clusters of the H1
      viruses (clusters I and II belonging to classical swine H1alpha, and cluster III
      belonging to classical swine H1gamma), and 2 clusters of the H3 viruses both
      belonging to human-like 1970s. The serological results indicated that swH1N1-06
      (H1 cluster I) is a suitable representative SIV for the HI test antigen to detect
      H1 SIV-specific antibodies in the Thai swine population, while both swH3N2-05 and
      swH3N2-07 should be used for Thai H3 SIV-specific antibody detection. The HI test
      results of swine sera collected from pigs in the 4 highest pig population
      provinces of Thailand indicated that the percentage of pigs seropositive to
      swH3N2-07 was highest compared to swH1N1-06, swH1N1-09, and swH3N2-05 (85.4%,
      50.1%, 18.6%, and 15.8%, respectively). It should be noted that countries lacking
      SIV genetic information should be concerned with determining the most suitable HI
      test antigens to use when performing the tests due to the genetic variation and
      limited cross-reaction of SIVs. The results of the current study demonstrated
      that HI tests should be implemented with the suitable field strains as the
      representative test antigen to ascertain accurate SIV serostatus in Thailand and
      that test antigens should be genetically analyzed and compared with circulating
      strains regularly.

PMID- 23166186
TI  - A comparison of family interventions to address adolescent risky behaviors: a
      literature review.
AB  - The purpose of this integrative review is to describe, compare, and synthesize
      traditional and computer-based family interventions that aim to change
      adolescents' risky sexual behaviors and substance abuse. Family interventions
      have been shown to generate protective effects for preventing adolescents from
      risky behaviors. It is not clear, however, whether there are significant
      differences or similarities in the designs and effects of traditional and
      computer-based family interventions. An integrative literature review was
      conducted to describe and compare the designs and effects of traditional and
      computer-based family interventions. Both interventions have generated
      significant effects on reducing risky behavior among adolescents. Interventions
      guided by theory, tailored to participants' culture/gender, and which included
      sufficient boosting dosages in their designs demonstrated significant short- or
      long-term effects in terms of reducing adolescents' risky behaviors. Regardless
      of delivery method, well-designed family interventions are noted to maximize
      familial protective effects and reduce risky behaviors.

PMID- 23166187
TI  - Diagnosis of acute deer tick virus encephalitis.
AB  - BACKGROUND: Deer tick virus (DTV) is a tick-borne flavivirus that has only
      recently been appreciated as a cause of viral encephalitis. We describe the
      clinical presentation of a patient who had DTV encephalitis diagnosed before
      death and survived for 8 months despite severe neurologic dysfunction. METHODS:
      Diagnosis was made from a cerebrospinal fluid specimen, using a flavivirus
      specific polymerase chain-reaction assay followed by sequence confirmation, and
      the phylogeny was analyzed. Serologic testing, including plaque reduction
      neutralization testing, was also performed. RESULTS: Molecular analysis indicated
      that the virus was closely related to 2 strains of DTV that had been detected in
      Ixodes scapularis ticks from Massachusetts in 1996 and in the brain of a patient
      from New York in 2007. CONCLUSIONS: DTV encephalitis should be considered in the
      differential diagnosis of encephalitis in geographic areas that are endemic for
      Lyme disease.

PMID- 23166189
TI  - The safety of amphotericin B lipid complex in patients with prior severe
      intolerance to liposomal amphotericin B.
AB  - The tolerability of amphotericin B lipid complex in patients with previous severe
      infusion reactions to liposomal amphotericin B is unclear. We reviewed the charts
      of 40 such patients at a tertiary care cancer center and found that amphotericin
      B lipid complex administration was uneventful in 34 patients (85% [95% confidence
      interval, 69%-93%]).

PMID- 23166188
TI  - The "decline and fall" of nontyphoidal salmonella in the United kingdom.
AB  - Remarkable changes in the epidemiology of human nontyphoidal salmonellosis have
      occurred in the United Kingdom over the last century. Between 1981 and 1991, the
      incidence of nontyphoidal salmonellosis in the United Kingdom rose by >170%,
      driven primarily by an epidemic of Salmonella enterica subspecies enterica
      serovar Enteritidis phage type (PT) 4, which peaked in 1993. Measures introduced
      to control this epidemic included legislation, food safety advice, and an
      industry-led vaccination program in broiler-breeder and laying poultry flocks.
      The incidence of Salmonella Enteritidis has been falling since 1997, and levels
      of Salmonella Enteritidis PT4 have fallen to preepidemic levels and have stayed
      low. The temporal relationship between vaccination programs and the reduction in
      human disease is compelling and suggests that these programs have made a major
      contribution to improving public health.

PMID- 23166191
TI  - Telaprevir to boceprevir switch highlights lack of cross-reactivity.
AB  - Hepatitis C viral protease inhibitors increase sustained virologic response rates
      compared to interferon and ribavirin but also add side effects. Telaprevir and
      boceprevir are structurally similar, and share cross-resistant mutations. This
      case report highlights successful management of telaprevir skin rash and anal
      discomfort by switching to boceprevir.

PMID- 23166192
TI  - The nose knows not: poor predictive value of stool sample odor for detection of
      Clostridium difficile.

PMID- 23166193
TI  - Birthweight in offspring of mothers with high prevalence of helminth and malaria
      infection in coastal Kenya.
AB  - Results of studies on the associations of maternal helminth infection and malaria
      helminth co-infection on birth outcomes have been mixed. A group of 696 pregnant
      women from the Kwale district in Kenya were recruited and tested for malaria and
      helminth infection at delivery. Birthweight was documented for 664 infants. A
      total of 42.7% of the mothers were infected with Plasmodium falciparum, 30.6%
      with Schistosoma haematobium, 36.2% with filariasis, 31.5% with hookworm, and
      5.9% with Trichuris trichiura; co-infection was present in 46.7%. Low birthweight
      (LBW) (weight < 2,500 grams) was present in 15.4% of the offspring, and 8.3% had
      a weight z-score <= 2 SD below the World Health Organization mean. Only gravida,
      age, and locale had a significant association with LBW. The high prevalence of
      maternal infection coupled with a higher than expected percentage of LBW
      highlight a need for further investigation of the association of maternal co
      infection with LBW.

PMID- 23166194
TI  - Seasonal differences in retinopathy-negative versus retinopathy-positive cerebral
      malaria.
AB  - Children with traditionally defined cerebral malaria (CM) can be subcategorized
      by the presence or absence of malaria retinopathy. We retrospectively reviewed
      the seasonal pattern of retinopathy status in patients admitted with CM in
      Blantyre, Malawi from 1997 to 2010. The proportion of children with CM who were
      retinopathy-positive was significantly greater during the peak seasonal rains
      when the community incidence of uncomplicated malaria is higher. This finding
      supports the hypothesis that retinopathy-negative and retinopathy-positive CM
      categories have different underlying etiologies.

PMID- 23166195
TI  - A cluster-randomized trial of insecticide-treated curtains for dengue vector
      control in Thailand.
AB  - The efficacy of insecticide-treated window curtains (ITCs) for dengue vector
      control was evaluated in Thailand in a cluster-randomized controlled trial. A
      total of 2,037 houses in 26 clusters was randomized to receive the intervention
      or act as control (no treatment). Entomological surveys measured Aedes
      infestations (Breteau index, house index, container index, and pupae per person
      index) and oviposition indices (mean numbers of eggs laid in oviposition traps)
      immediately before and after intervention, and at 3-month intervals over 12
      months. There were no consistent statistically significant differences in
      entomological indices between intervention and control clusters, although
      oviposition indices were lower (P < 0.01) in ITC clusters during the wet season.
      It is possible that the open housing structures in the study reduced the
      likelihood of mosquitoes making contact with ITCs. ITCs deployed in a region
      where this house design is common may be unsuitable for dengue vector control.

PMID- 23166196
TI  - Alterations in Plasmodium falciparum genetic structure two years after increased
      malaria control efforts in western Kenya.
AB  - The impact of malaria intervention measures (insecticide-treated net use and
      artemisinin combination therapy) on malaria genetics was investigated at two
      sites in western Kenya: an endemic lowland and an epidemic highland. The genetic
      structure of the parasite population was assessed by using microsatellites, and
      the prevalence of drug-resistant mutations was examined by using the polymerase
      chain reaction-restriction fragment length polymorphism method. Two years after
      intervention, genetic diversity remained high in both populations. A significant
      decrease in the prevalence of quintuple mutations conferring resistance to
      sulfadoxine-pyrimethamine was detected in both populations, but the mutation
      prevalence at codon 1246 of the Plasmodium falciparum multidrug resistance 1 gene
      had increased in the highland population. The decrease in sulfadoxine
      pyrimethamine-resistant mutants is encouraging, but the increase in P. falciparum
      multidrug resistance 1 gene mutations is worrisome because these mutations are
      linked to resistance to other antimalarial drugs. In addition, the high level of
      genetic diversity observed after intervention suggests transmission is still high
      in each population.

PMID- 23166197
TI  - Weather-driven variation in dengue activity in Australia examined using a process
      based modeling approach.
AB  - The impact of weather variation on dengue transmission in Cairns, Australia, was
      determined by applying a process-based dengue simulation model (DENSiM) that
      incorporated local meteorologic, entomologic, and demographic data. Analysis
      showed that inter-annual weather variation is one of the significant determinants
      of dengue outbreak receptivity. Cross-correlation analyses showed that DENSiM
      simulated epidemics of similar relative magnitude and timing to those
      historically recorded in reported dengue cases in Cairns during 1991-2009, (r =
      0.372, P < 0.01). The DENSiM model can now be used to study the potential impacts
      of future climate change on dengue transmission. Understanding the impact of
      climate variation on the geographic range, seasonality, and magnitude of dengue
      transmission will enhance development of adaptation strategies to minimize future
      disease burden in Australia.

PMID- 23166198
TI  - Case report: Molecular diagnosis of subcutaneous Spirometra erinaceieuropaei
      sparganosis in a Japanese immigrant.
AB  - We report a case of subcutaneous sparganosis in a 68-year-old female Japanese
      immigrant in Germany. The patient complained of a painless erythema caudal of the
      umbilicus with a palpable subcutaneous cherry-sized lump. Polymerase chain
      reaction on formalin-fixed parasite tissue identified Spirometra erinaceieuropaei
      as the causative agent; the proliferative form of sparganosis, which is caused by
      the branching and disseminating Sparganum proliferum, could, thus, be excluded.
      From the excised sparganum, an immunofluorescence test was established and
      revealed an antibody response directed against the parasite's tegument.
      Histological key features of the plerocercoid that facilitate diagnosis with
      different stains are presented.

PMID- 23166200
TI  - Ad libitum fluid intake does not prevent dehydration in suboptimally hydrated
      young soccer players during a training session of a summer camp.
AB  - There is a lack of studies concerning hydration status of young athletes
      exercising in the heat. PURPOSE: To assess preexercise hydration status in young
      soccer players during a summer sports camp and to evaluate body- water balance
      after soccer training sessions. METHODS: Initial hydration status was assessed in
      107 young male soccer players (age 11-16 yr) during the 2nd day of the camp.
      Seventy-two athletes agreed to be monitored during 2 more training sessions (3rd
      and 5th days of the camp) to calculate dehydration via changes in body weight,
      while water drinking was allowed ad libitum. Hydration status was assessed via
      urine specific gravity (USG), urine color, and changes in total body weight. Mean
      environmental temperature and humidity were 27.2 +/- 2  degrees C and 57% +/- 9%,
      respectively. RESULTS: According to USG values, 95 of 107 of the players were
      hypohydrated (USG >= 1.020) before practice. The prevalence of dehydration
      observed was maintained on both days, with 95.8% and 97.2% of the players being
      dehydrated after the training sessions on the 3rd and 5th days, respectively.
      Despite fluid availability, 54 of the 66 (81.8%) dehydrated players reduced their
      body weight (-0.35 +/- 0.04 kg) as a response to training, while 74.6% (47 out of
      the 63) further reduced their body weight (-0.22 +/- 0.03 kg) after training on
      the 5th day. CONCLUSION: Approximately 90% of the young soccer players who began
      exercising under warm weather conditions were hypohydrated, while drinking ad
      libitum during practice did not prevent further dehydration in already dehydrated
      players.

PMID- 23166199
TI  - Identification of Blastocystis subtype 1 variants in the Home for Girls, Bangkok,
      Thailand.
AB  - A cross-sectional study of Blastocystis infection was conducted to evaluate the
      prevalence, risk factors, and subtypes of Blastocystis at the Home for Girls,
      Bangkok, Thailand in November 2008. Of 370 stool samples, 118 (31.9%) were
      infected with Blastocystis. Genotypic characterization of Blastocystis was
      performed by polymerase chain reaction and sequence analysis of the partial small
      subunit ribosomal RNA (SSU rRNA) gene. Subtype 1 was the most predominant
      (94.8%), followed by subtype 6 (3.5%) and subtype 2 (1.7%). Sequence analyses
      revealed nucleotide polymorphisms for Blastocystis subtype 1, which were
      described as subtype 1/variant 1, subtype 1/variant 2. Blastocystis subtype
      1/variant 1 was the most predominant infection occurring in almost every house.
      The results showed that subtype analysis of Blastocystis was useful for molecular
      epidemiological study.

PMID- 23166201
TI  - Growth Hormone Responses to Consecutive Exercise Bouts with Ingestion of
      Carbohydrate plus Protein.
AB  - Endocrine responses to repeated exercise have hardly been investigated and no
      data are available regarding the mediating influence of nutrition. On three
      occasions, participants ran for 90 min at 70% VO2max (R1) before a second
      exhaustive treadmill run at the same intensity (R2; 91.6 +/- 17.9 min). During
      the intervening 4 h recovery, participants ingested either: (i) 0.8 g sucrose.kg
      1.h-1 with 0.3 g.kg-1.h-1 whey protein isolate (CHO-PRO); (ii) 0.8 g sucrose.kg
      1.h-1 (CHO) or; (iii) 1.1 g sucrose.kg-1.h-1 (CHO-CHO). The latter two solutions
      therefore matched the former for carbohydrate or for available energy,
      respectively. Serum growth hormone concentrations increased from 1.7+/-0.9 MUg.l
      1 to 16.7+/-7.8 MUg.l-1 during R1 considered across all treatments (means+/
      standard deviations; P<=0.01). Concentrations were similar immediately after R2
      irrespective of whether CHO or CHO-CHO was ingested (19+/-4 MUg.l-1 and 19+/
      5MUg.l-1, respectively), whereas ingestion of CHO-PRO produced an augmented
      response (31+/-4MUg.l-1; P<=0.05). Growth hormone binding protein concentrations
      were unaffected by R1 but increased similarly across all treatments during R2
      (414+/-202 pmol.l-1 to 577+/-167 pmol.l-1; P<=0.01), as was the case for plasma
      total testosterone (9.3+/-3.3 nmol.l-1 to 14.7+/-4.6 nmol.l-1; P<=0.01). There
      was an overall treatment effect for serum cortisol (P<=0.05), with no specific
      differences at any given time-point but lower concentrations immediately after R2
      with CHO-PRO (608+/-133 nmol.l-1) than CHO (796+/-278 nmol.l-1) or CHO-CHO (838+/
      134 nmol.l-1). Ingesting carbohydrate with added whey protein isolate during
      short-term recovery from 90 minutes of treadmill running increases the growth
      hormone response to a second exhaustive exercise bout of similar duration.

PMID- 23166202
TI  - Stable haemodynamics associated with no significant electrocardiogram
      abnormalities is a good prognostic factor of survival for acute type A aortic
      dissection repair.
AB  - OBJECTIVES: Acute type A aortic dissection (AAD) is a medical emergency with high
      mortality even with emergency repair. We explored the prognostic factors of in
      hospital mortality for AAD repair. METHODS: One hundred and thirty-three
      consecutive patients operated on for AAD between 1997 and 2011 were enrolled in
      our study. They were assigned to the in-hospital mortality or the survival group.
      We evaluated 101 variables to predict in-hospital mortality. All data were
      collected retrospectively. RESULTS: The 30-day mortality, including
      intraoperative deaths, was 12.8% (17/133 patients) and in-hospital mortality was
      18.0% (24/133). Univariate analysis disclosed 10 significant prognostic factors.
      Multivariate analysis confirmed that preoperative shock or hypotension (odds
      ratio (OR) = 4.71; P = 0.004), an initial 24 h of bleeding >1500 ml (OR = 5.17; P
      = 0.01) and age >= 75 years (OR = 3.70; P = 0.019) were independent prognostic
      factors of in-hospital mortality. On the contrary, an electrocardiogram (ECG)
      showing no abnormalities (OR = 0.22; P = 0.008) is a good prognostic factor for
      survival. Interestingly, patients with stable haemodynamics without abnormal ECG
      findings had an excellent result of 1.6% (1/63) in-hospital mortality.
      CONCLUSIONS: Stable haemodynamics and no significant abnormal ECG findings
      predicted excellent in-hospital survival. Cardiac surgeons and cardiologists
      should be aware of these positive predictors when treating patients diagnosed
      with AAD.

PMID- 23166203
TI  - A simple method for increasing levels of high-density lipoprotein cholesterol: a
      pilot study of combination aerobic- and resistance-exercise training.
AB  - Evidence suggests that physical activity has a beneficial effect of elevated high
      density lipoprotein cholesterol (HDL-C) on reducing coronary artery risk.
      However, previous studies show contrasting results for this association between
      different types of exercise training (i.e., aerobic, resistance, or combined
      aerobic and resistance training). The aim of this study was to determine which
      type of exercise training is more effective in increasing HDL-C levels. Forty
      obese men, age 18-29 yr, were randomized into 4 groups: an aerobic-training group
      (n = 10), a resistance-training group (n = 10), a combined-exercise-training
      group (n = 10), and a control group (n = 10). After a 12-wk exercise program,
      anthropometrics, blood biochemical variables, and physical-fitness components
      were compared with the data obtained at the baseline. Multiple-regression
      analysis was used to evaluate the association between different types of exercise
      training and changes in HDL-C while adjusting for potential confounders. The
      results showed that with the control group as the comparator, the effects of
      combined-exercise training (beta = 4.17, p < .0001), aerobic training (beta =
      3.65, p < .0001), and resistance training (beta = 2.10, p = .0001) were
      positively associated with increase in HDL-C after adjusting for potential
      confounders. Our findings suggested that a short-term exercise program can play
      an important role in increasing HDL-C levels; either aerobic or resistance
      training alone significantly increases the HDL-C levels, but the improvements are
      greatest with combined aerobic and resistance training.

PMID- 23166205
TI  - Photo Quiz. Primary amebic meningoencephalitis.

PMID- 23166210
TI  - 2012 ACCF/AHA/ACP/AATS/PCNA/SCAI/STS guideline for the diagnosis and management
      of patients with stable ischemic heart disease: executive summary: a report of
      the American College of Cardiology Foundation/American Heart Association task
      force on practice guidelines, and the American College of Physicians, American
      Association for Thoracic Surgery, Preventive Cardiovascular Nurses Association,
      Society for Cardiovascular Angiography and Interventions, and Society of Thoracic
      Surgeons.

PMID- 23166211
TI  - 2012 ACCF/AHA/ACP/AATS/PCNA/SCAI/STS guideline for the diagnosis and management
      of patients with stable ischemic heart disease: a report of the American College
      of Cardiology Foundation/American Heart Association task force on practice
      guidelines, and the American College of Physicians, American Association for
      Thoracic Surgery, Preventive Cardiovascular Nurses Association, Society for
      Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons.

PMID- 23166212
TI  - Bilateral internal mammary artery grafting enhances survival in diabetic
      patients: a 30-year follow-up of propensity score-matched cohorts.
AB  - BACKGROUND: The prevalence of diabetes mellitus is increasing at an unprecedented
      rate, affecting nearly 8% of the population. Previous studies have demonstrated a
      potential benefit for surgical over interventional revascularization in this
      group of patients. Similarly, studies have shown the superiority of bilateral
      internal mammary artery (BIMA) grafting over single internal mammary artery
      (SIMA) grafting in select populations. However, concerns about sternal wound
      infection have discouraged the use of BIMA grafting in diabetics. Therefore, we
      studied the long-term results of BIMA versus SIMA grafting in a large population
      of diabetic patients in whom BIMA grafting was broadly applied. METHODS AND
      RESULTS: Between February 1972 and May 1994, 1107 consecutive diabetic patients
      underwent coronary artery bypass grafting with either SIMA (n=646) or BIMA
      (n=461) grafting. Optimal matching with the propensity score was used to create
      matched SIMA (n=414) and BIMA (n=414) cohorts. Cross-sectional follow-up (6 weeks
      to 30.1 years; mean, 8.9 years) determined long-term survival. There was no
      difference in operative mortality, sternal wound infection, or total
      complications between matched SIMA and BIMA groups (operative mortality, 10 of
      414 [2.4%] versus 13 of 414 [3.1%]; P=0.279; sternal wound infection, 7 of 414
      [1.7%] versus 13 of 414 [3.1%]; P=0.179); total complications, 71 of 414 [17.1%]
      versus 71 of 414 [17.1%]; P=1.000). Late survival was significantly enhanced with
      the use of BIMA grafting (median survival: SIMA, 9.8 years versus BIMA, 13.1
      years; P=0.001). Use of BIMA was found to be associated with late survival on Cox
      regression (P=0.003). CONCLUSION: Compared with SIMA grafting, BIMA grafting in
      propensity score-matched patients provides diabetics with enhanced survival
      without any increase in perioperative morbidity or mortality.

PMID- 23166209
TI  - Impact of ancestry and common genetic variants on QT interval in African
      Americans.
AB  - BACKGROUND: Ethnic differences in cardiac arrhythmia incidence have been
      reported, with a particularly high incidence of sudden cardiac death and low
      incidence of atrial fibrillation in individuals of African ancestry. We tested
      the hypotheses that African ancestry and common genetic variants are associated
      with prolonged duration of cardiac repolarization, a central pathophysiological
      determinant of arrhythmia, as measured by the electrocardiographic QT interval.
      METHODS AND RESULTS: First, individual estimates of African and European ancestry
      were inferred from genome-wide single-nucleotide polymorphism (SNP) data in 7
      population-based cohorts of African Americans (n=12,097) and regressed on
      measured QT interval from ECGs. Second, imputation was performed for 2.8 million
      SNPs, and a genome-wide association study of QT interval was performed in 10
      cohorts (n=13,105). There was no evidence of association between genetic ancestry
      and QT interval (P=0.94). Genome-wide significant associations (P<2.5 * 10(-8))
      were identified with SNPs at 2 loci, upstream of the genes NOS1AP (rs12143842,
      P=2 * 10(-15)) and ATP1B1 (rs1320976, P=2 * 10(-10)). The most significant SNP in
      NOS1AP was the same as the strongest SNP previously associated with QT interval
      in individuals of European ancestry. Low probability values (P<10(-5)) were
      observed for SNPs at several other loci previously identified in genome-wide
      association studies in individuals of European ancestry, including KCNQ1, KCNH2,
      LITAF, and PLN. CONCLUSIONS: We observed no difference in duration of cardiac
      repolarization with global genetic indices of African American ancestry. In
      addition, our genome-wide association study extends the association of
      polymorphisms at several loci associated with repolarization in individuals of
      European ancestry to include individuals of African ancestry.

PMID- 23166213
TI  - Why did you not use both internal thoracic arteries?

PMID- 23166215
TI  - eComment. Should persistent N2/N3 non-small cell lung cancer be treated by
      surgery?

PMID- 23166216
TI  - eComment. The problem of anaemia correction in cardiac surgery patients.

PMID- 23166218
TI  - eComment. Retained temporary epicardial pacing wires in cardiac surgery.

PMID- 23166219
TI  - eComment. Early surgery in preventing stroke in left-sided infective
      endocarditis.

PMID- 23166220
TI  - eComment. Early surgery for patients with uncomplicated prosthetic valve
      endocarditis.

PMID- 23166221
TI  - eComment. Cardiopulmonary bypass and pregnancy.

PMID- 23166222
TI  - eComment. Surgical complications of permanent cardiac pacemaker insertion.

PMID- 23166223
TI  - eComment. Massive pulmonary air embolism during pacemaker implantation: better
      preoperative exams?

PMID- 23166224
TI  - eComment. Catheter-induced acute aortic syndrome.

PMID- 23166226
TI  - Recognizing the top 25 peer reviewers for the Journal of Virology.

PMID- 23166225
TI  - Sphingosine kinase 1 overexpression contributes to cetuximab resistance in human
      colorectal cancer models.
AB  - PURPOSE: Although the anti-EGF receptor (EGFR) monoclonal antibody cetuximab is
      an effective strategy in colorectal cancer therapy, its clinical use is limited
      by intrinsic or acquired resistance. Alterations in the "sphingolipid rheostat"
      the balance between the proapoptotic molecule ceramide and the mitogenic factor
      sphingosine-1-phosphate (S1P)-due to sphingosine kinase 1 (SphK1) overactivation
      have been involved in resistance to anticancer-targeted agents. Moreover, cross
      talks between SphK1 and EGFR-dependent signaling pathways have been described.
      EXPERIMENTAL DESIGN: We investigated SphK1 contribution to cetuximab resistance
      in colorectal cancer, in preclinical in vitro/in vivo models, and in tumor
      specimens from patients. RESULTS: SphK1 was found overexpressed and overactivated
      in colorectal cancer cells with intrinsic or acquired resistance to cetuximab.
      SphK1 contribution to resistance was supported by the demonstration that SphK1
      inhibition by N,N-dimethyl-sphingosine or silencing via siRNA in resistant cells
      restores sensitivity to cetuximab, whereas exogenous SphK1 overexpression in
      sensitive cells confers resistance to these agents. Moreover, treatment of
      resistant cells with fingolimod (FTY720), a S1P receptor (S1PR) antagonist,
      resulted in resensitization to cetuximab both in vitro and in vivo, with
      inhibition of tumor growth, interference with signal transduction, induction of
      cancer cells apoptosis, and prolongation of mice survival. Finally, a correlation
      between SphK1 expression and cetuximab response was found in colorectal cancer
      patients.

PMID- 23166228
TI  - Genome sequence of canine parvovirus strain SC02/2011, isolated from a puppy with
      severe diarrhea in south China.
AB  - A widespread hemorrhagic gastroenteritis in young dogs occurred in South China. A
      virulent field canine parvovirus (CPV) strain, SC02/2011, was isolated from a
      puppy showing enteric signs in Guangdong, China. The genome of CPV strain
      SC02/2011 was sequenced and analyzed, which will promote a better understanding
      of the molecular epidemiology and genetic diversity of CPV field isolates in
      South China.

PMID- 23166229
TI  - Complete genome sequence of Cronobacter sakazakii bacteriophage vB_CsaM_GAP161.
AB  - Cronobacter sakazakii is an opportunistic pathogen that causes infant meningitis
      and is often associated with milk-based infant formula. We have fully sequenced
      the genome of a newly isolated lytic C. sakazakii myovirus, vB_CsaM_GAP161,
      briefly named GAP161. It consists of 178,193 bp and has a G+C content of 44.5%. A
      total of 277 genes, including 275 open reading frames and two tRNA-encoding
      genes, were identified. This phage is closely related to coliphages RB16 and RB43
      and Klebsiella pneumoniae phage KP15.

PMID- 23166230
TI  - Complete genome sequence of dengue virus serotype 2 Cosmopolitan genotype strain
      in Guangdong, China.
AB  - Here we report the complete genome sequence of a dengue virus serotype 2 (DENV-2)
      strain, GZ40, isolated in Guangdong, China, in 2010. A phylogenetic analysis
      classified GZ40 into the Cosmopolitan genotype, while previous Chinese DENV-2
      isolates belong to the Asian I genotype. The reemergence of the Cosmopolitan
      genotype of DENV-2 in China deserves further investigation.

PMID- 23166231
TI  - Complete genome sequence of human respiratory syncytial virus genotype A with a
      72-nucleotide duplication in the attachment protein G gene.
AB  - The complete genome sequence of human respiratory syncytial virus genotype A
      (HRSV-A) with a 72-nucleotide duplication in the C-terminal part of the
      attachment protein G gene was determined and analyzed. The genome was 15,277 bp
      in length, and 0.46 to 6.03% variations were identified at the nucleotide level
      compared with the previously reported complete genome of HRSV-A. Characterization
      of the genome will improve understanding of the diversity of the HRSV-A major
      antigens and enable an in-depth analysis of its genetics.

PMID- 23166232
TI  - Complete genome sequence of a recombinant nephropathogenic infectious bronchitis
      virus strain in China.
AB  - Recently, nephropathogenic infectious bronchitis virus (IBV) outbreaks have
      occurred in commercial broiler flocks and have been associated with a high
      incidence and morbidity in China. The CK/CH/Zhejiang/06/10 strain (IBV-YX10) was
      isolated from a 12-day-old broiler chicken in a flock of chickens with swollen
      speckled kidneys and distended ureters filled with uric acid in China in 2010.
      Here we reported the complete genomic sequence of the IBV-YX10 which was a
      natural recombinant nephropathogenic infectious bronchitis virus strain. These
      findings will contribute additional insights into the molecular characteristics
      of evolving IBV genomes and the need for effective control of IBV in China.

PMID- 23166233
TI  - Complete genome sequence of Newcastle disease virus mesogenic vaccine strain R2B
      from India.
AB  - Mesogenic vaccine strains of Newcastle disease virus (NDV) are widely used in
      many countries of Asia and Africa to control the Newcastle disease of poultry. In
      India, the mesogenic strain R2B was introduced in 1945; it protects adult
      chickens that have been preimmunized with a lentogenic vaccine virus and provides
      long-lasting immunity. In this article, we report the complete genome sequence of
      the hitherto unsequenced Indian vaccine virus strain R2B. The viral genome is
      15,186 nucleotides in length and contains the polybasic amino acid motif in the
      fusion protein cleavage site, indicating that this vaccine strain has evolved
      from a virulent virus. Phylogenetic analysis of this mesogenic vaccine virus
      classified it with the viruses belonging to genotype III of the class cluster II
      of NDV.

PMID- 23166234
TI  - Complete genome sequence of an amur virus isolated from Apodemus peninsulae in
      Northeastern China.
AB  - Amur virus was recently identified as the causative agent of hemorrhagic fever
      with renal syndrome. Here we report the complete genome sequence of an Amur virus
      isolated from Apodemus peninsulae in Northeastern China. The sequence information
      provided here is critical for the molecular epidemiology and evolution of Amur
      virus in China.

PMID- 23166235
TI  - Complete genome sequence of a recombinant Marek's disease virus field strain with
      one reticuloendotheliosis virus long terminal repeat insert.
AB  - Marek's disease virus (MDV) Chinese strain GX0101, isolated in 2001 from a
      vaccinated flock of layer chickens with severe tumors, was the first reported
      recombinant MDV field strain with one reticuloendotheliosis virus (REV) long
      terminal repeat (LTR) insert. GX0101 belongs to very virulent MDV (vvMDV) but has
      higher horizontal transmission ability than the vvMDV strain Md5. The complete
      genome sequence of GX0101 is 178,101 nucleotides (nt) and contains only one REV
      LTR insert at a site 267 nt upstream of the sorf2 gene. Moreover, GX0101 has 5
      repeats of a 217-nt fragment in its terminal repeat short (TRS) region and 3
      repeats in internal repeat short (IRS) region, compared to the other 10 strains
      with only 1 or 2 repeats in both TRS and IRS.

PMID- 23166236
TI  - Complete genome of a novel porcine astrovirus.
AB  - Astroviruses have been widely described in mammalian and avian species. Here, we
      report a complete genome sequence of a novel porcine astrovirus (PoAstV) isolated
      from a porcine fecal sample in China. The genome consists of 6,611 nucleotides,
      excluding the 3' poly(A) tail, and has two open reading frames (ORFs). ORF1 maps
      between nucleotide positions 19 and 4211 and encodes a 1,396-amino-acid (aa)
      polyprotein precursor consisting of nonstructural protein and putative RNA
      dependent RNA polymerase, and ORF2 maps between nucleotide positions 4202 and
      6531 and encodes a 775-aa polyprotein which is a capsid precursor protein. The
      genome sequence of the virus was distinct enough from those of the known PoAstVs
      to be considered a novel sequence. Phylogenetic analysis based on the predicted
      amino acid sequence of the complete capsid region showed that this strain may be
      a novel porcine astrovirus.

PMID- 23166237
TI  - Complete genome sequence of equine herpesvirus type 9.
AB  - Equine herpesvirus type 9 (EHV-9), which we isolated from a case of epizootic
      encephalitis in a herd of Thomson's gazelles (Gazella thomsoni) in 1993, has been
      known to cause fatal encephalitis in Thomson's gazelle, giraffe, and polar bear
      in natural infections. Our previous report indicated that EHV-9 was similar to
      the equine pathogen equine herpesvirus type 1 (EHV-1), which mainly causes
      abortion, respiratory infection, and equine herpesvirus myeloencephalopathy. We
      determined the genome sequence of EHV-9. The genome has a length of 148,371 bp
      and all 80 of the open reading frames (ORFs) found in the genome of EHV-1. The
      nucleotide sequences of the ORFs in EHV-9 were 86 to 95% identical to those in
      EHV-1. The whole genome sequence should help to reveal the neuropathogenicity of
      EHV-9.

PMID- 23166238
TI  - Complete genome of a porcine calicivirus strain in Anhui province, China, is
      significantly shorter than that of the other Chinese strain.
AB  - Caliciviruses that cause diarrhea have been reported in both industrial and
      developing countries, including China, in recent years. Here, we report the
      complete genome of a porcine calicivirus strain, Ah-1, which is prevalent in
      swine groups in Anhui Province. This viral genome is 7,342 nucleotides (nt) long,
      excluding the poly(A) of the 3' end, which is 202 nt shorter in the 3'
      untranslated region (UTR) than that of the other Chinese porcine calicivirus
      strain (Ch-sw-sav1; GenBank accession number FJ387164), previously isolated in
      the Shanghai area, China, though they shared 98.8% sequence identity over the
      whole genome excluding the 202-nt-shorter region.

PMID- 23166239
TI  - Complete genome sequence of novel porcine epidemic diarrhea virus strain GD-1 in
      China.
AB  - Porcine epidemic diarrhea virus (PEDV) infection, which causes acute diarrhea and
      dehydration in suckling piglets, has become a serious problem for the swine
      industry of China in recent years. In this study, a virulent PEDV strain, GD-1,
      was obtained from fecal samples from suckling piglets that suffered from severe
      diarrhea in 2011 in Guangdong, China. Here we describe the complete genome
      sequence of strain GD-1, which may be helpful in further understanding the
      molecular epidemiology and genetic diversity of PEDV field isolates in China.

PMID- 23166240
TI  - Complete genomes of three human bocavirus strains from children with
      gastroenteritis and respiratory tract illnesses in Jiangsu, China.
AB  - Human bocavirus (HBoV) is a newly discovered parvovirus associated with acute
      respiratory tract illness (ARTI) and gastrointestinal illness. No previous
      reports indicated the presence of HBoV infection in Jiangsu Province, China. Here
      we report three complete genomic sequences of HBoV strains from children with
      gastroenteritis and respiratory tract illnesses in Jiangsu, China. Phylogenetic
      analysis indicated that the three HBoV strains in the present study belong to the
      HBoV1 lineage, where jz-42 clustered separately, forming a single branch, while
      zj-68 and zj-92 existed in two separate branches, clustering with several other
      Chinese HBoV1 strains.

PMID- 23166241
TI  - Complete genome sequencing of a velogenic viscerotropic avian paramyxovirus 1
      isolated from pheasants (Pucrasia macrolopha) in Lahore, Pakistan.
AB  - We report the complete genome sequence of avian paramyxovirus 1 (APMV-1) isolated
      from an acute and highly contagious outbreak in pheasants (Pucrasia macrolopha)
      in Lahore, Pakistan. Biological and serological characterization showed a
      velogenic strain of APMV-1, which was further confirmed by the sequence analysis
      of the cleavage site in the fusion protein. Complete genome sequencing and
      phylogenetic analysis indicated that this isolate belonged to genotype VII,
      specifically to subgenotype VIIa, and clustered closely with isolates
      characterized from Indonesia. Notably, the isolate showed significant differences
      from previously characterized APMV-1 from Pakistani commercial and rural chicken.

PMID- 23166242
TI  - Genome sequence of Cronobacter sakazakii myovirus vB_CsaM_GAP31.
AB  - Cronobacter sakazakii is a pathogen that predominantly infects immunocompromised
      individuals, especially infants, where it causes meningitis. The genome of lytic
      C. sakazakii myovirus vB_CsaM_GAP31 has been fully sequenced. It consists of
      147,940 bp and has a G+C content of 46.3%. A total of 295 genes, including 269
      open reading frames and 26 tRNA genes, were identified. This phage is related to
      Salmonella phage PVP-SE1 and coliphages vB_EcoM-FV3 and rV5.

PMID- 23166243
TI  - Complete genome sequence of Bp7, an Escherichia coli bacteriophage with a wide
      host range.
AB  - Chicken colibacillosis is caused by some pathogenic Escherichia coli strains.
      Thirty-five pathogenic antibiotic-resistant E. coli strains were used in the host
      range detection of bacteriophage Bp7. The phage showed a wide range of E. coli
      hosts (46%). The complete genome of bacteriophage Bp7 was sequenced, assembled,
      and analyzed. The results revealed a linear double-stranded DNA sequence of
      168,066 bp harboring 791 open reading frames. The major findings from its
      annotation are described.

PMID- 23166244
TI  - Complete genome sequence of a duck astrovirus discovered in eastern China.
AB  - We report here the complete genome sequence of a duck astrovirus (DAstV) isolated
      from a dead duckling in eastern China. Sequence analyses indicated that the
      genome of the astrovirus possessed a typical astrovirus organization. Comparison
      of the partial polymerase gene sequences of DAstV-1 and DAstV-2 showed that the
      astrovirus shared 94.4% and 64.2% nucleotide identity, respectively. The whole
      nucleotide sequence of the astrovirus had the highest homology with the sequence
      of DAstV-1 strain C-NGB (98.7%). Therefore, the strain we describe here is a
      DAstV-1 isolate.

PMID- 23166245
TI  - Complete genome sequence of a mink calicivirus in China.
AB  - We report the complete genome sequence of a novel calicivirus isolated from a
      diseased mink in China. The complete viral genome is approximately 8.4 kb in
      length and consists of three open reading frames. The availability of the
      complete genome sequence is helpful for further investigation into the molecular
      characteristics and epidemiology of calicivirus in mink.

PMID- 23166246
TI  - Genetic characterization of a novel recombinant H5N2 avian influenza virus
      isolated from chickens in Tibet.
AB  - In this report, a novel H5N2 avian influenza virus (AIV) was isolated from
      chickens in Tibet in 2010, western China. Phylogenetic analysis demonstrated that
      it was a natural reassortant between H9N2 and H5N1 subtypes. It is of note that
      this virus has an HP genotype with HA, PB2, M, and NS genes homologous to those
      of A/peregrine falcon/Hong Kong/2142/2008(H5N1)-like HPAIV isolated from dead
      wild birds. Publishing this genome information will contribute to the
      investigation of avian influenza epidemiology and to further research of AIV's
      biological properties.

PMID- 23166247
TI  - Complete genome sequence of the english isolate of rat cytomegalovirus (Murid
      herpesvirus 8).
AB  - The complete genome of the English isolate of rat cytomegalovirus (RCMV-E) was
      determined. RCMV-E has a 202,946-bp genome with noninverting repeats but without
      terminal repeats. Thus, it differs significantly in size and genomic arrangement
      from closely related rodent cytomegaloviruses (CMVs). To account for the
      differences between the rat CMV isolates of Maastricht and England, RCMV-E was
      classified as Murid herpesvirus 8 by the International Committee on Taxonomy of
      Viruses.

PMID- 23166248
TI  - Complete genome sequence of IME15, the first T7-like bacteriophage lytic to pan
      antibiotic-resistant Stenotrophomonas maltophilia.
AB  - T7-like bacteriophages are a class of virulent bacteriophages which have a
      clearer genetic background and smaller genomes than other phages. In addition, it
      grows faster and is easier to culture than other phages. At present, the numbers
      of available T7-like bacteriophage genomes and Stenotrophomonas maltophilia
      genomes are small, and IME15 is the first T7-like virulent Stenotrophomonas phage
      whose sequence has been reported. It shows effective lysis of S. maltophilia.
      Here we announce its complete genome, and major findings from its annotation are
      described.

PMID- 23166249
TI  - Comparative genomic analysis of duck enteritis virus strains.
AB  - The icosahedral virion of duck enteritis virus (DEV) is roughly spherical and
      approximately 150 nm in diameter. Here, we describe the genomic features of DEV
      CHv together with a draft genome sequence and its annotation, highlighting the
      homogeneity and heterogeneity of this genome in comparison with its reference
      genomes.

PMID- 23166250
TI  - Complete genome sequence of Klebsiella pneumoniae phage JD001.
AB  - Klebsiella pneumoniae is a member of the family Enterobacteriaceae, opportunistic
      pathogens that are among the eight most prevalent infectious agents in hospitals.
      The emergence of multidrug-resistant strains of K. pneumoniae has became a public
      health problem globally. To develop an effective antimicrobial agent, we isolated
      a bacteriophage, named JD001, from seawater and sequenced its genome. Comparative
      genome analysis of phage JD001 with other K. pneumoniae bacteriophages revealed
      that phage JD001 has little similarity to previously published K. pneumoniae
      phages KP15, KP32, KP34, and phiKO2. Here we announce the complete genome
      sequence of JD001 and report major findings from the genomic analysis.

PMID- 23166251
TI  - Complete genome sequencing of four geographically diverse strains of Batai virus.
AB  - Batai virus (BATV) is a widely distributed but poorly studied member of the
      Orthobunyavirus genus in the family Bunyaviridae and is of particular interest as
      a known participant in natural reassortment events. Both research and
      surveillance efforts on this and other related viruses have been hampered by the
      lack of available full-length sequence data covering all three genomic segments.
      Here, we report the complete genome sequence of four BATV strains (MM2222,
      Chittoor/IG-20217, UgMP-6830, and MS50) isolated from various geographical
      locations. Based on these data, we have determined that strain MS50 is in fact
      unrelated to BATV and likely represents as a novel genotype in the genus
      Orthobunyavirus.

PMID- 23166252
TI  - Complete genome sequencing of mosquito and human isolates of Ngari virus.
AB  - Ngari virus (NRIV) is a recently described, naturally occurring reassortant
      between two other orthobunyaviruses, Bunyamwera virus (BUNV) and Batai virus
      (BATV). Intriguingly, this reassortment was associated with the acquisition of
      heightened virulence, although the molecular basis for this is not understood.
      Here we report the first complete genome sequences of Ngari virus. We include
      five isolates from various geographical locations, as well as samples isolated
      from both mosquitos and human cases. Based on an analysis of these sequence data,
      NRIVs are clearly genetically distinct from all known BUNV and BATV strains but
      are very closely related to one another regardless of their source.

PMID- 23166253
TI  - Complete genome sequence of a duck hepatitis a virus type 3 identified in eastern
      China.
AB  - We report here the complete genome sequence of a novel duck hepatitis A virus
      type 3 (DHAV-3) isolated from a dead Cherry Valley duckling in eastern China. The
      whole genomic nucleotide sequence and polyprotein amino acid sequence of the
      virus had higher homology with those of Chinese DHAV-3 isolates, medium homology
      with those of Korean DHAV-3 isolates, and the lowest homology with those of
      Vietnamese isolate DN2. The result indicated that the genetic evolution of DHAV-3
      isolates had obvious geographical features.

PMID- 23166254
TI  - Complete genome sequence of a subgenotype VIId Newcastle disease virus
      circulating predominantly in chickens in China.
AB  - At least 11 genotypes of class II viruses have been identified since the
      discovery of Newcastle disease virus (NDV) in 1926. Here, we reported the
      complete genome sequence of a prevalent NDV variant from China, belonging to
      subgenotype VIId in class II. The similar viruses have been the predominant
      strains circulating in China for the past decade, which occupied over 80% of
      Chinese prevalent strains and were phylogenetically different from currently
      available vaccines.

PMID- 23166255
TI  - Genome sequence of temperate Vibrio parahaemolyticus bacteriophage vB_VpaS_MAR10.
AB  - Vibrio parahaemolyticus is recognized as one of the main causes of human
      gastroenteritis associated with seafood. We have fully sequenced the genome of a
      newly isolated phage, vB_VpaS_MAR10, which lysed 61.9% of the V. parahaemolyticus
      strains tested. Phage MAR10 is a temperate siphovirus, and its genome consists of
      double-stranded DNA (dsDNA) with a size of 78,751 bp, a G+C content of 49.70%,
      and 104 open reading frames. Bioinformatic analysis shows that phage MAR10 is
      closely related to Vibrio phage SSP002.

PMID- 23166256
TI  - Complete genome sequence of Seoul virus isolated from Rattus norvegicus in the
      Democratic People's Republic of Korea.
AB  - Seoul virus (SEOV) is responsible for 25% of cases of hemorrhagic fever with
      renal syndrome in Asia. Here we report the complete genome of strain DPRK08. The
      sequence information provided here is useful for understanding the molecular
      character of SEOV in the Democratic People's Republic of Korea (DPRK) and the
      circulation of SEOV in East Asia.

PMID- 23166257
TI  - Complete genome sequence analysis of a Newcastle disease virus isolated from a
      wild egret.
AB  - We report here the complete genomic sequence of a novel Newcastle disease virus
      (NDV) strain, egret/China/Guangxi/2011, isolated from an egret in Guangxi
      Province, southern China. A phylogenetic analysis based on a fusion gene
      comparison with different NDV strains revealed that egret/China/Guangxi/2011 was
      phylogenetically close to genotype VIIa NDV, and the deduced amino acid sequence
      was (112)R-R-R-K-R-F(117) at the fusion protein cleavage site. The whole
      nucleotide sequence had the highest homology (93.3%) with the sequence of strain
      chicken/Sukorejo/019/10 (GenBank accession number HQ697255). This study will help
      us to understand the epidemiology and molecular characteristics of Newcastle
      disease virus in a migratory egret.

PMID- 23166258
TI  - Complete genome sequence analysis of human echovirus type 30 isolated in China.
AB  - We report here the complete genome sequence of a human echovirus type 30 strain
      ECV30/GX10/05 isolated in Guangxi, China, in 2010. Phylogenetic analysis showed
      that ECV30/GX10/05 was closely related to a Korean strain isolated in 2008. The
      sequence information will help in an understanding of the molecular epidemiology
      and evolution of echovirus.

PMID- 23166259
TI  - Complete genome sequence of a Vero cell-adapted isolate of porcine epidemic
      diarrhea virus in eastern China.
AB  - In early 2012, a widespread porcine epidemic diarrhea virus (PEDV) occurred in
      eastern China. A cell-adapted isolate, SD-M, was at the four-passage level of
      virulent field strain SD, which was isolated from a 2-day-old dead suckling
      piglet that had suffered from severe diarrhea in Shandong Province, China. We
      report here the complete genome sequence of SD-M. This sequence will promote a
      better understanding of the molecular pathogenesis of PEDV.

PMID- 23166260
TI  - Genome sequence of a new Streptomyces coelicolor generalized transducing
      bacteriophage, PhiCAM.
AB  - Streptomyces coelicolor is a model system for the study of Streptomyces, a genus
      of bacteria responsible for the production of many clinically important
      antibiotics. Here we report the genome sequence of PhiCAM, a new S. coelicolor
      generalized transducing bacteriophage, isolated from a soil sample originating
      from Lincolnshire, United Kingdom. Many open reading frames within PhiCAM shared
      high levels of similarity to a prophage from Salinispora tropica and a putative
      prophage in Streptomyces sp. strain C.

PMID- 23166261
TI  - Complete genome sequence of IME11, a new N4-like bacteriophage.
AB  - N4-like bacteriophages are a class of virulent Podoviridae phages for which few
      genome sequences are present in GenBank. IME11, a novel lytic Escherichia
      bacteriophage with a wide host range, was isolated, and the whole genome was
      sequenced. It has a circular double-stranded DNA genome of 72,570 bp. Genomic
      analysis showed that it resembles another Escherichia phage, vB_EcoP_G7C. Here we
      announce its complete genome and major findings from its annotation.

PMID- 23166262
TI  - Complete genome sequence of a virulent porcine epidemic diarrhea virus strain.
AB  - In recent years, acute outbreaks of epizootic diarrhea have occurred on many
      swine farms in China. Although the putative causative virus of the disease was
      not isolated, the genomic sequence of porcine epidemic diarrhea virus (PEDV) was
      consistently detected from feces of diseased pigs by reverse transcription-PCR
      (RT-PCR). Here we report a complete genome sequence of PEDV which is apparently
      different from those of early PEDV circulated in Chinese swine herds.

PMID- 23166263
TI  - Complete genome sequence of a highly pathogenic porcine reproductive and
      respiratory syndrome virus NM1 strain from northern China.
AB  - NM1 is a highly pathogenic North American-type porcine reproductive and
      respiratory syndrome virus (PRRSV). The complete genome sequence shows that NM1
      shares high sequence identity (99.2 to 99.4%) to other HP-PRRSV isolates,
      containing two discontinuous deletions, a 1-amino-acid deletion at position 481
      and a 29-amino-acid deletion at positions 533 to 651, in nonstructural protein 2.

PMID- 23166264
TI  - Complete genome sequence of an H10N5 avian influenza virus isolated from pigs in
      central China.
AB  - An avian H10N5 influenza virus, A/swine/Hubei/10/2008/H10N5, was isolated from
      pigs in the Hubei Province of central China. Homology and phylogenetic analyses
      of all eight gene segments demonstrated that the strain was wholly of avian
      origin and closely homologous to the Eurasian lineage avian influenza virus. To
      our knowledge, this is the first report of interspecies transmission of an avian
      H10N5 influenza virus to domestic pigs under natural conditions.

PMID- 23166265
TI  - Complete genome sequence of a novel porcine parvovirus in China.
AB  - The porcine parvovirus JT strain (PPV-JT) was isolated from a piglet showing
      nonsuppurative myocarditis in Shandong, China, in 2010. The complete genomic
      sequence of PPV-JT, 4,941 bp long, was determined from clones made from
      replicative form (RF) DNA. The genomic analysis demonstrated that the PPV-JT
      might be involved in a recombination event, which will help us understand the
      molecular characteristics and evolutionary of PPV in China.

PMID- 23166266
TI  - Complete genome sequence analysis of an H6N1 avian influenza virus isolated from
      Guangxi pockmark ducks.
AB  - We report here the complete genomic sequence of a novel H6N1 avian influenza
      virus strain, A/Duck/Guangxi/GXd-5/2010(H6N1), isolated from pockmark ducks in
      Guangxi Province, Southern China. All of the 8 gene segments of
      A/Duck/Guangxi/GXd-5/2010(H6N1) are attributed to the Eurasian lineage; the amino
      acid motif of the cleavage site between HA1 and HA2 was P-Q-I-E-T-R-G. These are
      typical characteristics of the low-pathogenicity avian influenza virus. This
      study will help to understand the epidemiology and molecular characteristics of
      avian influenza virus in ducks.

PMID- 23166267
TI  - Complete genome sequence of recombinant porcine circovirus type 2 strain SD-3.
AB  - We report here the genome sequence of a recombinant porcine circovirus type 2
      strain SD-3, isolated from a commercial swine farm with an outbreak of
      postweaning multisystemic wasting syndrome (PMWS) in pigs in Shandong Province of
      China. The complete circular genome of this isolate is 1,767 nucleotides in
      length. This recombinant isolate has the ORF1 regions from PCV2a viruses and ORF2
      regions from PCV2b. The findings will help us to understand the molecular
      evolution of porcine circovirus type 2 and the relationship between porcine
      circovirus type 2 and disease.

PMID- 23166268
TI  - Complete genome sequence of T4-Like Escherichia coli bacteriophage HX01.
AB  - Phage T4 is among the best-characterized biological systems (S. Kanamaru and F.
      Arisaka, Seikagaku 74:131-135, 2002; E. S. Miller et al., Microbiol. Mol. Biol.
      Rev. 67:86-156, 2003; W. B. Wood and H. R. Revel, Bacteriol. Rev. 40:847-868,
      1976). To date, several genomes of T4-like bacteriophages are available in public
      databases but without any APEC bacteriophages (H. Jiang et al., Arch. Virol.
      156:1489-1492, 2011; L. Kaliniene, V. Klausa, A. Zajanckauskaite, R. Nivinskas,
      and L. Truncaite, Arch. Virol. 156:1913-1916, 2011; J. H. Kim et al., Vet.
      Microbiol. 157:164-171, 2012; W. C. Liao et al., J. Virol. 85:6567-6578, 2011).
      We isolated a bacteriophage from a duck factory, named HX01, that infects avian
      pathogenic Escherichia coli (APEC). Sequence and morphological analyses revealed
      that phage HX01 is a T4-like bacteriophage and belongs to the family Myoviridae.
      Here, we announce the complete genome sequence of phage HX01 and report the
      results of our analysis.

PMID- 23166269
TI  - Complete genome sequence of Serratia plymuthica bacteriophage PhiMAM1.
AB  - A virulent bacteriophage (PhiMAM1) that infects Serratia plymuthica was isolated
      from the natural environment and characterized. Genomic sequence analysis
      revealed a circular double-stranded DNA sequence of 157,834 bp, encoding 198
      proteins and 3 tRNAs. The PhiMAM1 genome shows high homology to previously
      reported ViI-like enterobacterial bacteriophage genomes.

PMID- 23166270
TI  - Complete genome sequence of the novel lytic avian pathogenic coliphage NJ01.
AB  - Bacteriophages of the C3 morphotype, characterized by very long heads that exceed
      their width several times, are extremely rare among the Podoviridae family
      members and constitute only 0.5% of over 5,500 phages that have been examined by
      the electron microscope (H. W. Ackermann, Arch. Virol. 152:227-243, 2007; H. W.
      Ackermann, Arch. Virol. 146:843-857, 2001). To date, among those phages proven to
      be C3, only coliphage phiEco32, Lactococcus phage KSY1, Vibrio phage 71A-6, and
      Salmonella enterica phage 7-11, but no avian pathogenic Escherichia coli (APEC)
      bacteriophages, have been completely sequenced (A. Chopin, H. Deveau, S. D.
      Ehrlich, S. Moineau, and M. C. Chopin, Virology 365:1-9, 2007; S. A. Khan, et
      al., Mol. Cell Probes 15:61-69, 2001; A. M. Kropinski, E. J. Lingohr, H. W.
      Ackermann, Arch. Virol. 156:149-151, 2011; D. Savalia, et al., J. Mol. Biol.
      377:774-789, 2008) and are available in public databases. We isolated a
      bacteriophage from a scale duck market in Nanjing, Jiangsu province, named NJ01,
      that infects APEC. Sequence and morphological analyses revealed that phage NJ01
      is a C3-like bacteriophage and belongs to the Podoviridae family. Here, we
      announce the complete genome sequence of phage NJ01 and submit the results of our
      analysis.

PMID- 23166271
TI  - Complete genome sequence of the bacteriophage YMC01/01/P52 PAE BP, which causes
      lysis of verona integron-encoded metallo-beta-lactamase-producing, carbapenem
      resistant Pseudomonas aeruginosa.
AB  - Multidrug-resistant Pseudomonas aeruginosa commonly causes serious nosocomial
      infections. In this study, a novel lytic bacteriophage belonging to a member of
      the family Podoviridae, YMC01/01/P52 PAE BP, which infects carbapenem-resistant
      Pseudomonas aeruginosa, was isolated and characterized. YMC01/01/P52 PAE BP
      genome was analyzed by whole-genome sequencing and putative function
      identification. The bacteriophage genome consists of a double-stranded linear DNA
      genome of 49,381 bp with a GC content of 62.16%.

PMID- 23166272
TI  - Complete genome sequence of a novel natural recombinant H5N5 influenza virus from
      ducks in central China.
AB  - We reported the complete genome sequence of an H5N5 avian influenza virus (AIV)
      that was first isolated from duck in central China in 2010. Genomic sequence and
      phylogenetic analyses showed that this virus was a recombinant between H5N1 AIV
      circulated in southeastern Asia and an N5 subtype influenza virus. These data are
      beneficial for investigating the epidemiology and ecology of AIVs in central
      China.

PMID- 23166273
TI  - Complete genome sequence of a novel H4N1 influenza virus isolated from a pig in
      central China.
AB  - Pigs are proposed to be "mixing vessel" hosts that can produce genetically novel
      reassortant viruses with pandemic potential. The appearance of any novel
      influenza viruses among pigs should pose concerns for human health. Here, we
      report the complete genome sequence of a novel H4N1 influenza virus
      [A/Swine/HuBei/06/2009(H4N1)] isolated from a pig in Central China in 2009. The
      genomic sequence analysis indicates that this virus is a wholly avian-original
      influenza virus. Each gene may come from different avian influenza viruses
      outside mainland China, suggesting the role of migratory birds in the dispersal
      of influenza virus.

PMID- 23166274
TI  - Complete genome sequence of wide-host-range Staphylococcus aureus phage JD007.
AB  - Methicillin-resistant Staphylococcus aureus-related infections have become a
      serious problem worldwide. Bacteriophage therapy is an alternative approach
      against this threat. S. aureus phage JD007, which belongs to the Myoviridae
      family according to transmission electron microscopic imaging, could lyse nearly
      30% of the S. aureus strains from Ruijin Hospital, Shanghai, China, and was
      isolated from chicken feces in Shanghai, China. The complete genome showed that
      JD007 is a linear, double-stranded DNA phage 141,836 bp in length with a GC
      content of 30.4% encoding 217 open reading frames. A BLAST search of the JD007
      genome revealed that it was very similar to that of phage GH15.

PMID- 23166275
TI  - Complete genome sequence of porcine reproductive and respiratory syndrome virus
      strain ZCYZ isolated from hybrid wild boars.
AB  - A serologic investigation of porcine reproductive and respiratory syndrome virus
      (PRRSV) in hybrid wild boar herds was conducted during 2008-2009. PRRSV isolates
      with novel genetic markers were recovered. Experimental infection of pigs
      indicated that hybrid wild boars are involved in the epidemiology of PRRSV.

PMID- 23166276
TI  - Complete genome sequence of a moderately pathogenic porcine reproductive and
      respiratory syndrome virus variant strain.
AB  - Porcine reproductive and respiratory syndrome (PRRS) has become one of the most
      economically important diseases to the global pork industry. The etiological
      agent is the PRRS virus (PRRSV). In the spring of 2006, a highly pathogenic
      porcine reproductive and respiratory syndrome virus (HP-PRRSV) appeared in China
      and caused heavy economic losses. Here we report the complete genomic sequence of
      a novel PRRSV variant with 174 amino acid deletions in the nonstructural protein
      2 (nsp2) gene.

PMID- 23166277
TI  - Complete genome sequence of porcine circovirus 2b strain Shandong.
AB  - Shandong is a porcine circovirus 2b (PCV2b) strain that was isolated and purified
      from tissue samples from pigs with postweaning multisystemic wasting syndrome
      (PMWS) in the Shandong Province of China. Here, we report the complete genome
      sequence of strain Shandong, which may aid in understanding the molecular
      characteristics of this strain.

PMID- 23166278
TI  - Complete genomic sequences of rabbit hemorrhagic disease virus G1 strains
      isolated in the European rabbit original range.
AB  - The complete genomic sequences of rabbit hemorrhagic disease virus (RHDV) strains
      isolated in 1995 (CB137) and 2006 (CB194) from wild European rabbits from
      Portugal are described. The strains were isolated in the original range of the
      European rabbit and assigned to genogroup 1 (G1), which is known to have
      persisted only in the Iberian Peninsula. ORF2 of isolate CB137 might encode a
      shorter minor structural protein, VP10.

PMID- 23166279
TI  - Complete genome sequence of an infectious bronchitis virus chimera between
      cocirculating heterotypic strains.
AB  - To date, multiple serotypes and genotypes of infectious bronchitis virus (IBV)
      have been isolated and identified. In order to provide more information on the
      viral evolution of IBVs, a new virulent strain named GX-NN09032, isolated from
      Guangxi, China, in 2009, was sequenced, and phylogenetic and recombination
      analyses were conducted. Furthermore, potential recombination events associated
      with GX-NN09032 were found in four IBV strains, including GX-YL5, DY07,
      CK/CH/SD09/005, TC07-2. The present study suggested that GX-NN09032 might
      contribute to the emergence of modern IBV variants through recombination.

PMID- 23166281
TI  - Considering cost in primary care.

PMID- 23166282
TI  - The next wave in family practice.

PMID- 23166283
TI  - Toss out those theories of medicine.

PMID- 23166284
TI  - Grappling with family practice complexities.

PMID- 23166285
TI  - The road to competitive generic drug prices in Canada.

PMID- 23166286
TI  - Logical process = smarter prescribing.

PMID- 23166287
TI  - Family docs: the power of numbers.

PMID- 23166288
TI  - Why is controlling blood pressure after stroke so difficult?

PMID- 23166289
TI  - Canadian physician supply on uptick.

PMID- 23166290
TI  - Intraosseous access.

PMID- 23166291
TI  - Cardiovascular disease after Escherichia coli O157:H7 gastroenteritis.
AB  - BACKGROUND: Escherichia coli O157:H7 is one cause of acute bacterial
      gastroenteritis, which can be devastating in outbreak situations. We studied the
      risk of cardiovascular disease following such an outbreak in Walkerton, Ontario,
      in May 2000. METHODS: In this community-based cohort study, we linked data from
      the Walkerton Health Study (2002-2008) to Ontario's large healthcare databases.
      We included 4 groups of adults: 3 groups of Walkerton participants (153 with
      severe gastroenteritis, 414 with mild gastroenteritis, 331 with no
      gastroenteritis) and a group of 11 263 residents from the surrounding communities
      that were unaffected by the outbreak. The primary outcome was a composite of
      death or first major cardiovascular event (admission to hospital for acute
      myocardial infarction, stroke or congestive heart failure, or evidence of
      associated procedures). The secondary outcome was first major cardiovascular
      event censored for death. Adults were followed for an average of 7.4 years.
      RESULTS: During the study period, 1174 adults (9.7%) died or experienced a major
      cardiovascular event. Compared with residents of the surrounding communities, the
      risk of death or cardiovascular event was not elevated among Walkerton
      participants with severe or mild gastroenteritis (hazard ratio [HR] for severe
      gastroenteritis 0.74, 95% confidence interval [CI] 0.38-1.43, mild
      gastroenteritis HR 0.64, 95% CI 0.42-0.98). Compared with Walkerton participants
      who had no gastroenteritis, risk of death or cardiovascular event was not
      elevated among participants with severe or mild gastroenteritis. INTERPRETATION:
      There was no increase in the risk of cardiovascular disease in the decade
      following acute infection during a major E. coli O157:H7 outbreak.

PMID- 23166292
TI  - Neural correlates of the encoding of multimodal contextual features.
AB  - Functional magnetic resonance imaging (fMRI) was employed to identify neural
      regions engaged during the encoding of contextual features belonging to different
      modalities. Subjects studied objects that were presented to the left or right of
      fixation. Each object was paired with its name, spoken in either a male or a
      female voice. The test requirement was to discriminate studied from unstudied
      pictures and, for each picture judged old, to retrieve its study location and the
      gender of the voice that spoke its name. Study trials associated with accurate
      rather than inaccurate location memory demonstrated enhanced activity in the
      fusiform and parahippocampal cortex and the hippocampus and reduced activity (a
      negative subsequent memory effect) in the medial occipital cortex. Successful
      encoding of voice information was associated with enhanced study activity in the
      right middle superior temporal sulcus and activity reduction in the right
      superior frontal cortex. These findings support the proposal that encoding of a
      contextual feature is associated with enhanced activity in regions engaged during
      its online processing. In addition, they indicate that negative subsequent memory
      effects can also demonstrate feature-selectivity. Relative to other classes of
      study trials, trials for which both contextual features were later retrieved
      demonstrated enhanced activity in the lateral occipital complex and reduced
      activity in the temporo-parietal junction. These findings suggest that
      multifeatural encoding was facilitated when the study item was processed
      efficiently and study processing was not interrupted by redirection of attention
      toward extraneous events.

PMID- 23166293
TI  - Relationship between increase in astrocytic GLT-1 glutamate transport and late
      LTP.
AB  - Na+-dependent high-affinity glutamate transporters have important roles in the
      maintenance of basal levels of glutamate and clearance of glutamate during
      synaptic transmission. Interestingly, several studies have shown that basal
      glutamate transport displays plasticity. Glutamate uptake increases in
      hippocampal slices during early long-term potentiation (E-LTP) and late long-term
      potentiation (L-LTP). Four issues were addressed in this research: Which
      glutamate transporter is responsible for the increase in glutamate uptake during
      L-LTP? In what cell type in the hippocampus does the increase in glutamate uptake
      occur? Does a single type of cell contain all the mechanisms to respond to an
      induction stimulus with a change in glutamate uptake? What role does the increase
      in glutamate uptake play during L-LTP? We have confirmed that GLT-1 is
      responsible for the increase in glutamate uptake during L-LTP. Also, we found
      that astrocytes were responsible for much, if not all, of the increase in
      glutamate uptake in hippocampal slices during L-LTP. Additionally, we found that
      cultured astrocytes alone were able to respond to an induction stimulus with an
      increase in glutamate uptake. Inhibition of basal glutamate uptake did not affect
      the induction of L-LTP, but inhibition of the increase in glutamate uptake did
      inhibit both the expression of L-LTP and induction of additional LTP. It seems
      likely that heightened glutamate transport plays an ongoing role in the ability
      of hippocampal circuitry to code and store information.

PMID- 23166294
TI  - The MYC-associated protein CDCA7 is phosphorylated by AKT to regulate MYC
      dependent apoptosis and transformation.
AB  - Cell division control protein A7 (CDCA7) is a recently identified target of MYC
      dependent transcriptional regulation. We have discovered that CDCA7 associates
      with MYC and that this association is modulated in a phosphorylation-dependent
      manner. The prosurvival kinase AKT phosphorylates CDCA7 at threonine 163,
      promoting binding to 14-3-3, dissociation from MYC, and sequestration to the
      cytoplasm. Upon serum withdrawal, induction of CDCA7 expression in the presence
      of MYC sensitized cells to apoptosis, whereas CDCA7 knockdown reduced MYC
      dependent apoptosis. The transformation of fibroblasts by MYC was reduced by
      coexpression of CDCA7, while the non-MYC-interacting protein Delta(156-187)-CDCA7
      largely inhibited MYC-induced transformation. These studies provide insight into
      a new mechanism by which AKT signaling to CDCA7 could alter MYC-dependent growth
      and transformation, contributing to tumorigenesis.

PMID- 23166295
TI  - Link of NTR-mediated spliceosome disassembly with DEAH-box ATPases Prp2, Prp16,
      and Prp22.
AB  - The DEAH-box ATPase Prp43 is required for disassembly of the spliceosome after
      the completion of splicing or after the discard of the spliceosome  due to a
      splicing defect. Prp43 associates with Ntr1 and Ntr2 to form the NTR complex and
      is recruited to the spliceosome via the interaction of Ntr2 and U5 component
      Brr2. Ntr2 alone can bind to U5 and to the spliceosome. To understand how NTR
      might mediate the disassembly of spliceosome intermediates, we arrested the
      spliceosome at various stages of the assembly pathway and assessed  its
      susceptibility to disassembly. We found that NTR could catalyze the disassembly
      of affinity-purified spliceosomes arrested specifically after the ATP-dependent
      action of DEAH-box ATPase Prp2, Prp16, or Prp22 but not at steps before the
      action of these ATPases or upon their binding to the spliceosome. These results
      link spliceosome disassembly to the functioning of splicing ATPases. Analysis of
      the binding of Ntr2 to each splicing complex has revealed that the presence of
      Prp16 and Slu7, which also interact with Brr2, has a negative impact on Ntr2
      binding. Our study provides insights into the mechanism by which NTR can be
      recruited to the spliceosome to mediate the disassembly of spliceosome
      intermediates when the spliceosome pathway is retarded, while disassembly is
      prevented  in normal reactions.

PMID- 23166296
TI  - Steroidogenic factor 1 (NR5A1) maintains centrosome homeostasis in steroidogenic
      cells by restricting centrosomal DNA-dependent protein kinase activation.
AB  - Steroidogenic factor 1 (SF-1 or NR5A1) is a nuclear receptor that controls
      adrenogenital cell growth and differentiation. Adrenogenital primordial cells
      from SF-1 knockout mice die of apoptosis, but the mechanism by which SF-1
      regulates cell survival is not entirely clear. Besides functioning in the
      nucleus, SF-1 also resides in the centrosome and controls centrosome homeostasis.
      Here, we show that SF-1 restricts centrosome overduplication by inhibiting
      aberrant activation of DNA-dependent protein kinase (DNA-PK) in the centrosome.
      SF-1 was found to be associated with Ku70/Ku80 only in the centrosome,
      sequestering them from the catalytic subunit of DNA-PK (DNA-PKcs). In the absence
      of SF-1, DNA-PKcs was recruited to the centrosome and activated, causing aberrant
      activation of centrosomal Akt and cyclin-dependent kinase 2 (CDK2)/cyclin A and
      leading to centrosome overduplication. Centrosome overduplication caused by SF-1
      depletion was averted by the elimination of DNA-PKcs, Ku70/80, or cyclin A or by
      the inhibition of CDK2 or Akt. In the nucleus, SF-1 did not interact with
      Ku70/80, and SF-1 depletion did not activate a nuclear DNA damage response.
      Centriole biogenesis was also unaffected. Thus, centrosomal DNA-PK signaling
      triggers centrosome overduplication, and this centrosomal event, but not the
      nuclear DNA damage response, is controlled by SF-1.

PMID- 23166298
TI  - Sonic hedgehog-dependent induction of microRNA 31 and microRNA 150 regulates
      Mycobacterium bovis BCG-driven toll-like receptor 2 signaling.
AB  - Hedgehog (HH) signaling is a significant regulator of cell fate decisions during
      embryogenesis, development, and perpetuation of various disease conditions.
      Testing whether pathogen-specific HH signaling promotes unique innate recognition
      of intracellular bacteria, we demonstrate that among diverse Gram-positive or
      Gram-negative microbes, Mycobacterium bovis BCG, a vaccine strain, elicits a
      robust activation of Sonic HH (SHH) signaling in macrophages. Interestingly,
      sustained tumor necrosis factor alpha (TNF-alpha) secretion by macrophages was
      essential for robust SHH activation, as TNF-alpha(-/-) macrophages exhibited
      compromised ability to activate SHH signaling. Neutralization of TNF-alpha or
      blockade of TNF-alpha receptor signaling significantly reduced the infection
      induced SHH signaling activation both in vitro and in vivo. Intriguingly,
      activated SHH signaling downregulated M. bovis BCG-mediated Toll-like receptor 2
      (TLR2) signaling events to regulate a battery of genes associated with divergent
      functions of M1/M2 macrophages. Genome-wide expression profiling as well as
      conventional gain-of-function or loss-of-function analysis showed that SHH
      signaling-responsive microRNA 31 (miR-31) and miR-150 target MyD88, an adaptor
      protein of TLR2 signaling, thus leading to suppression of TLR2 responses. SHH
      signaling signatures could be detected in vivo in tuberculosis patients and M.
      bovis BCG-challenged mice. Collectively, these investigations identify SHH
      signaling to be what we believe is one of the significant regulators of host
      pathogen interactions.

PMID- 23166297
TI  - Saccharomyces cerevisiae Env7 is a novel serine/threonine kinase 16-related
      protein kinase and negatively regulates organelle fusion at the lysosomal
      vacuole.
AB  - Membrane fusion depends on conserved components and is responsible for organelle
      biogenesis and vesicular trafficking. Yeast vacuoles are dynamic structures
      analogous to mammalian lysosomes. We report here that yeast Env7 is a novel
      palmitoylated protein kinase ortholog that negatively regulates vacuolar membrane
      fusion. Microscopic and biochemical studies confirmed the localization of tagged
      Env7 at the vacuolar membrane and implicated membrane association via the
      palmitoylation of its N-terminal Cys13 to -15. In vitro kinase assays established
      Env7 as a protein kinase. Site-directed mutagenesis of the Env7 alanine-proline
      glutamic acid (APE) motif Glu269 to alanine results in an unstable kinase-dead
      allele that is stabilized and redistributed to the detergent-resistant fraction
      by interruption of the proteasome system in vivo. Palmitoylation-deficient
      Env7C13-15S is also kinase dead and mislocalizes to the cytoplasm. Microscopy
      studies established that env7Delta is defective in maintaining fragmented
      vacuoles during hyperosmotic response and in buds. ENV7 function is not redundant
      with a similar role of vacuolar membrane kinase Yck3, as the two do not share a
      substrate, and ENV7 is not a suppressor of yck3Delta. Bayesian phylogenetic
      analyses strongly support ENV7 as an ortholog of the gene encoding human STK16, a
      Golgi apparatus protein kinase with undefined function. We propose that Env7
      function in fusion/fission dynamics may be conserved within the endomembrane
      system.

PMID- 23166299
TI  - Oligodeoxynucleotide binding to (CTG) . (CAG) microsatellite repeats inhibits
      replication fork stalling, hairpin formation, and genome instability.
AB  - (CTG)(n) . (CAG)(n) trinucleotide repeat (TNR) expansion in the 3' untranslated
      region of the dystrophia myotonica protein kinase (DMPK) gene causes myotonic
      dystrophy type 1. However, a direct link between TNR instability, the formation
      of noncanonical (CTG)(n) . (CAG)(n) structures, and replication stress has not
      been demonstrated. In a human cell model, we found that (CTG)(45) . (CAG)(45)
      causes local replication fork stalling, DNA hairpin formation, and TNR
      instability. Oligodeoxynucleotides (ODNs) complementary to the (CTG)(45) .
      (CAG)(45) lagging-strand template eliminated DNA hairpin formation on leading-
      and lagging-strand templates and relieved fork stalling. Prolonged cell culture,
      emetine inhibition of lagging-strand synthesis, or slowing of DNA synthesis by
      low-dose aphidicolin induced (CTG)(45) . (CAG)(45) expansions and contractions.
      ODNs targeting the lagging-strand template blocked the time-dependent or emetine
      induced instability but did not eliminate aphidicolin-induced instability. These
      results show directly that TNR replication stalling, replication stress, hairpin
      formation, and instability are mechanistically linked in vivo.

PMID- 23166300
TI  - TCPTP regulates SFK and STAT3 signaling and is lost in triple-negative breast
      cancers.
AB  - Tyrosine phosphorylation-dependent signaling, as mediated by members of the
      epidermal growth factor receptor (EGFR) family (ErbB1 to -4) of protein tyrosine
      kinases (PTKs), Src family PTKs (SFKs), and cytokines such as interleukin-6 (IL
      6) that signal via signal transducer and activator of transcription 3 (STAT3), is
      critical to the development and progression of many human breast cancers. EGFR,
      SFKs, and STAT3 can serve as substrates for the protein tyrosine phosphatase
      TCPTP (PTPN2). Here we report that TCPTP protein levels are decreased in a subset
      of breast cancer cell lines in vitro and that TCPTP protein is absent in a large
      proportion of "triple-negative" primary human breast cancers. Homozygous TCPTP
      deficiency in murine mammary fat pads in vivo is associated with elevated SFK and
      STAT3 signaling, whereas TCPTP deficiency in human breast cancer cell lines
      enhances SFK and STAT3 signaling. On the other hand, TCPTP reconstitution in
      human breast cancer cell lines severely impaired cell proliferation and
      suppressed anchorage-independent growth in vitro and xenograft growth in vivo.
      These studies establish TCPTP's potential to serve as a tumor suppressor in human
      breast cancer.

PMID- 23166302
TI  - Author response: Different efficacy of propranolol in mice with oxygen-induced
      retinopathy: could differential effects of propranolol be related to differences
      in mouse strains?

PMID- 23166301
TI  - TAK1 is essential for osteoclast differentiation and is an important modulator of
      cell death by apoptosis and necroptosis.
AB  - Transforming growth factor beta (TGF-beta)-activated kinase 1 (TAK1), a mitogen
      activated protein 3 (MAP3) kinase, plays an essential role in inflammation by
      activating the IkappaB kinase (IKK)/nuclear factor kappaB (NF-kappaB) and stress
      kinase (p38 and c-Jun N-terminal kinase [JNK]) pathways in response to many
      stimuli. The tumor necrosis factor (TNF) superfamily member receptor activator of
      NF-kappaB ligand (RANKL) regulates osteoclastogenesis through its receptor, RANK,
      and the signaling adaptor TRAF6. Because TAK1 activation is mediated through
      TRAF6 in the interleukin 1 receptor (IL-1R) and toll-like receptor (TLR)
      pathways, we sought to investigate the consequence of TAK1 deletion in RANKL
      mediated osteoclastogenesis. We generated macrophage colony-stimulating factor (M
      CSF)-derived monocytes from the bone marrow of mice with TAK1 deletion in the
      myeloid lineage. Unexpectedly, TAK1-deficient monocytes in culture died rapidly
      but could be rescued by retroviral expression of TAK1, inhibition of receptor
      interacting protein 1 (RIP1) kinase activity with necrostatin-1, or simultaneous
      genetic deletion of TNF receptor 1 (TNFR1). Further investigation using TAK1
      deficient mouse embryonic fibroblasts revealed that TNF-alpha-induced cell death
      was abrogated by the simultaneous inhibition of caspases and knockdown of RIP3,
      suggesting that TAK1 is an important modulator of both apoptosis and necroptosis.
      Moreover, TAK1-deficient monocytes rescued from programmed cell death did not
      form mature osteoclasts in response to RANKL, indicating that TAK1 is
      indispensable to RANKL-induced osteoclastogenesis. To our knowledge, we are the
      first to report that mice in which TAK1 has been conditionally deleted in
      osteoclasts develop osteopetrosis.

PMID- 23166303
TI  - Fluid in equals fluid out--evidence for circulating fluid fluxes in the lens.

PMID- 23166305
TI  - MicroRNA-145 post-transcriptionally regulates the expression and function of P
      glycoprotein in intestinal epithelial cells.
AB  - P-glycoprotein (P-gp/MDR1) is a multispecific efflux transporter regulating the
      pharmacokinetics of various drugs. Although P-gp expression in the small
      intestine is elevated after liver ischemia-reperfusion (I/R) injury, the
      regulatory mechanism remains to be clarified. MicroRNAs (miRNAs) play an
      important role in the post-transcriptional regulation of the expression of drug
      transporters. Here, we investigated the intestinal expression profile of miRNAs
      after liver I/R and the role of miRNAs in the post-transcriptional regulation of
      P-gp in intestinal epithelial cells. Microarray analysis showed that microRNA-145
      (miR-145) level was decreased in the small intestine of I/R rats. This
      downregulation of miR-145 was further confirmed by real-time polymerase chain
      reaction. In silico analysis revealed that 3'-untranslated regions (UTRs) of rat
      Mdr1a, mouse Mdr1a, and human MDR1 mRNA retain binding sites for miR-145.
      Luciferase assays using MDR1 3'-UTR reporter plasmid in HEK293 cells showed that
      luciferase activity was decreased by the overexpression of miR-145, and the
      deletion of miR-145 binding site within MDR1 3'-UTR abolished this decreased
      luciferase activity. The downregulation of miR-145 in Caco-2 cells, an epithelial
      cell line derived from human colon, increased P-gp expression and efflux activity
      of rhodamine 123, but not MDR1 mRNA level. These findings demonstrated that miR
      145 negatively regulates the expression and function of P-gp through the
      repression of mRNA by direct interaction on the 3'-UTR of MDR1 mRNA. In addition,
      the downregulation of miR-145 should significantly contribute to the elevated
      intestinal P-gp expression after liver I/R. Our results provide new insight into
      the post-transcriptional regulation of intestinal P-gp.

PMID- 23166306
TI  - Modulation of dendritic AMPA receptor mRNA trafficking by RNA splicing and
      editing.
AB  - RNA trafficking to dendrites and local translation are crucial processes for
      superior neuronal functions. To date, several alpha-amino-3-hydroxy-5-methyl-4
      isoxazolepropionate receptor (AMPAR) mRNAs have been detected in dendrites and
      are subject to local protein synthesis. Here, we report the presence of all AMPAR
      GluA1-4 mRNAs in hippocampal and cortical rat synaptic spines by
      synaptoneurosomes analysis. In particular, we showed that dendritic AMPAR mRNAs
      are present in the Flip versions in the cortex and hippocampus. To further
      confirm these data, we demonstrate, using in situ hybridization, the dendritic
      localization of the GluA2 Flip isoform in vitro and in vivo, whereas the Flop
      variant is restricted mainly to the soma. In addition, we report that dendritic
      AMPA mRNAs are edited at low levels at their R/G sites; this result was also
      supported with transfection experiments using chimeric GluA2 DNA vectors, showing
      that transcripts carrying an unedited nucleotide at the R/G site, in combination
      with the Flip exon, are more efficiently targeted to dendrites when compared with
      the edited-Flip versions. Our data show that post-transcriptional regulations
      such as RNA splicing, editing and trafficking might be mutually coordinated and
      that the localization of different AMPAR isoforms in dendrites might play a
      functional role in the regulation of neuronal transmission.

PMID- 23166307
TI  - Deep sequencing reveals unique small RNA repertoire that is regulated during head
      regeneration in Hydra magnipapillata.
AB  - Small non-coding RNAs such as miRNAs, piRNAs and endo-siRNAs fine-tune gene
      expression through post-transcriptional regulation, modulating important
      processes in development, differentiation, homeostasis and regeneration. Using
      deep sequencing, we have profiled small non-coding RNAs in Hydra magnipapillata
      and investigated changes in small RNA expression pattern during head
      regeneration. Our results reveal a unique repertoire of small RNAs in hydra. We
      have identified 126 miRNA loci; 123 of these miRNAs are unique to hydra. Less
      than 50% are conserved across two different strains of Hydra vulgaris tested in
      this study, indicating a highly diverse nature of hydra miRNAs in contrast to
      bilaterian miRNAs. We also identified siRNAs derived from precursors with perfect
      stem-loop structure and that arise from inverted repeats. piRNAs were the most
      abundant small RNAs in hydra, mapping to transposable elements, the annotated
      transcriptome and unique non-coding regions on the genome. piRNAs that map to
      transposable elements and the annotated transcriptome display a ping-pong
      signature. Further, we have identified several miRNAs and piRNAs whose expression
      is regulated during hydra head regeneration. Our study defines different classes
      of small RNAs in this cnidarian model system, which may play a role in
      orchestrating gene expression essential for hydra regeneration.

PMID- 23166308
TI  - Decline in renal functioning is associated with longitudinal decline in global
      cognitive functioning, abstract reasoning and verbal memory.
AB  - BACKGROUND: Decreased estimated glomerular filtration rate (eGFR) and higher
      serum creatinine (sCR) levels have been associated with longitudinal decline in
      global mental status measures. Longitudinal data describing change in multiple
      domains of cognitive functioning are needed in order to determine which specific
      abilities are most affected in individuals with impaired renal function. METHODS:
      We conducted a 5-year longitudinal study with 590 community-living individuals
      (mean age 62.1 years, 60.2% female, 93.2% white, 11.4% with diabetes mellitus,
      mean eGFR 78.4 mL/min/1.73 m2) free from dementia, acute stroke and end-stage
      renal disease. To measure longitudinal change-over-time, cognitive performance
      measures were regressed on eGFR adjusting for baseline eGFR and cognitive
      performance, comorbidity and vascular risk factors. Outcome measures were scores
      from 17 separate tests of cognitive abilities that were used to index 5
      theoretically relevant domains: verbal episodic memory, visual-spatial
      organization and memory, scanning and tracking, working memory and similarities
      (abstract reasoning). RESULTS: Declines in eGFR values were associated with
      cognitive declines, when adjusted for eGFR and cognitive function scores at
      baseline. Change in renal functioning over time was related to change observed in
      global cognitive ability [b=0.21SD decline per unit ln(eGFR), 95% CI: 0.04-0.38,
      P=.018], verbal episodic memory [b=0.28 SD decline per unit ln(eGFR), 95% CI:
      0.02-0.54, P=0.038] and abstract reasoning [b=0.36 SD decline per unit ln(eGFR),
      95% CI: 0.04-0.67, P=0.025]. Decline in cognitive functioning in association with
      declining renal functioning was observed despite statistical adjustment for
      demographic variables and CVD risk factors and the exclusion of persons with
      dementia or a history of acute stroke. CONCLUSIONS: Early detection of mild to
      moderate kidney disease is an important public health concern with regard to
      cognitive decline.

PMID- 23166309
TI  - Phosphate attenuates the anti-proteinuric effect of very low-protein diet in CKD
      patients.
AB  - BACKGROUND: High phosphate levels attenuate nephroprotection through angiotensin
      converting enzyme inhibition in patients with proteinuric chronic kidney disease
      (CKD). Whether this phenomenon holds true for other nephroprotective
      interventions like very-low-protein diet (VLPD) is unknown. METHODS: We tested
      the hypothesis that phosphate interferes with the anti-proteinuric response to
      VLPD in a non-randomized, sequential study in 99 proteinuric CKD patients who
      sequentially underwent low-protein diet (LPD; 0.6 g/kg) and VLPD (0.3 g/kg)
      supplemented with keto-analogues, each for periods longer than 1 year. RESULTS:
      Serum phosphate significantly reduced during VLPD (3.2 +/- 0.6 mg/dL) when
      compared with LPD (3.7 +/- 0.6 mg/dL, P < 0.001), an effect paralleled by a
      substantial decline in phosphate excretion (LPD, 649 +/- 180 mg/day; VLPD, 462 +/
      97 mg/day; P < 0.001). The median proteinuria during LPD was 1910 mg/24 h
      (interquartile range: 1445-2376 mg/24 h) and reduced to 987 mg/24 h (656-1300
      mg/24 h) during VLPD (P < 0.001). No significant change in the estimated
      glomerular filtration rate (eGFR) was observed during the two diet periods. In
      linear mixed models including the diagnosis of renal disease, eGFR, 24-h urine
      sodium and urea and other potential confounders, there was a strong interaction
      between serum phosphate (P = 0.04) and phosphaturia (P < 0.001) with the anti
      proteinuric response to VLPD. Accordingly, 24-h proteinuria reduced modestly in
      patients who maintained relatively higher serum phosphate levels or relatively
      higher phosphaturia to be maximal in those who achieved the lowest level of serum
      and urine phosphate. CONCLUSION: Phosphate is an important modifier of the anti
      proteinuric response to VLPD. Reducing phosphate burden may decrease proteinuria
      and slow the progression of renal disease in CKD patients, an issue that remains
      to be tested in specific clinical trials.

PMID- 23166310
TI  - COSMOS: the dialysis scenario of CKD-MBD in Europe.
AB  - BACKGROUND: Chronic kidney disease-mineral and bone disorders (CKD-MBD) are
      important complications of CKD5D patients that are associated with mortality.
      METHODS: COSMOS is a multicentre, open cohort, prospective, observational 3-year
      study carried out in haemodialysis patients from 20 European countries during
      2005-07. The present article describes the main characteristics of the European
      dialysis population, the current practice for the prevention, diagnosis and
      treatment of secondary hyperparathyroidism and the differences across different
      European regions. RESULTS: The haemodialysis population in Europe is an aged
      population (mean age 64.8+/-14.2 years) with a high prevalence of diabetes
      (29.5%) and cardiovascular disease (76.0%), and 28.7% of patients have been on
      haemodialysis more than 5 years. Patients from the former Eastern countries are
      younger (59.3+/-14.3 versus 66.0+/-13.9), having a lower proportion of diabetics
      (24.1 versus 30.7%). There were relevant differences in the frequency of
      measurement of the main CKD-MBD biochemical parameters [Ca, P and parathyroid
      hormone (PTH)] and the Eastern countries showed a poorer control of these
      biochemical parameters (K/DOQI and K/DIGO targets). Overall, 48.0% of the
      haemodialysis patients received active vitamin D treatment. Calcitriol use
      doubled that of alfacalcidiol in the Mediterranean countries, whereas the
      opposite was found in the non-Mediterranean countries. The criteria followed to
      perform parathyroidectomy were different across Europe. In the Mediterranean
      countries, the level of serum PTH considered to perform parathyroidectomy was
      higher than in non-Mediterranean countries; as a result, in the latter, more
      parathyroidectomies were performed in the year previous to inclusion to COSMOS.
      CONCLUSIONS: The COSMOS baseline results show important differences across Europe
      in the management of CKD-MBD.

PMID- 23166311
TI  - Impact and perceptions of tobacco tax increase in remote Australian Aboriginal
      communities.
AB  - INTRODUCTION: We sought to assess the impact of a 25% tax excise rise on tobacco
      sales in Aboriginal communities in remote Australia and to explore local
      perceptions about tobacco tax rises and their impact. METHODS: Tobacco sales data
      were collected from 18 stores in small remote Aboriginal communities from October
      2009 to December 2010. Sales in the 7 months before and after the tax increase
      were compared. Interviews were conducted with 54 informants in 6 communities.
      RESULTS: There was a nonsignificant 2.2% average reduction (95% CI = -5 to 10) in
      total tobacco sold in a store in the 7 months after the price increase compared
      with the 7 months before the price increase, with a large variation across the 18
      stores. The magnitude of this apparent impact may have been reduced by seasonal
      effects. There were increased demands to share cigarettes, with a perception that
      there was increased reliance on those with more disposable income to purchase
      cigarettes for other smokers. The main reasons given for not quitting or reducing
      smoking were dependence, the normative nature of smoking, and the lack of support
      to quit. All Aboriginal interviewees supported price increases as important in
      reducing smoking. CONCLUSIONS: The wide confidence interval around our estimated
      reduction in consumption means that the tax increase could have either been
      associated or not with a reduction in consumption. Future excise rises are
      supported but should be carefully monitored in Australian Indigenous populations.

PMID- 23166312
TI  - Nordion clarifies agreement with JSC Isotope of Russia.

PMID- 23166313
TI  - Splenectomy: reducing the risk of infection.

PMID- 23166315
TI  - Splenectomy: reducing the risk of infection.

PMID- 23166316
TI  - Clarifying the assistance provided by the CMPA.

PMID- 23166318
TI  - Differential regulation of extracellular tissue inhibitor of metalloproteinases-3
      levels by cell membrane-bound and shed low density lipoprotein receptor-related
      protein 1.
AB  - Tissue inhibitor of metalloproteinases-3 (TIMP-3) plays a key role in regulating
      extracellular matrix turnover by inhibiting matrix metalloproteinases (MMPs),
      adamalysins (ADAMs), and adamalysins with thrombospondin motifs (ADAMTSs). We
      demonstrate that levels of this physiologically important inhibitor can be
      regulated post-translationally by endocytosis. TIMP-3 was endocytosed and
      degraded by a number of cell types including chondrocytes, fibroblasts, and
      monocytes, and we found that the endocytic receptor low density lipoprotein
      receptor-related protein-1 (LRP-1) plays a major role in TIMP-3 internalization.
      However, the cellular uptake of TIMP-3 significantly slowed down after 10 h due
      to shedding of LRP-1 from the cell surface and formation of soluble LRP-1 (sLRP
      1)-TIMP-3 complexes. Addition of TIMP-3 to HTB94 human chondrosarcoma cells
      increased the release of sLRP-1 fragments of 500, 215, 160, and 110 kDa into the
      medium in a concentration-dependent manner, and all of these fragments were able
      to bind to TIMP-3. TIMP-3 bound to sLRP-1, which was resistant to endocytosis,
      retained its inhibitory activity against metalloproteinases. Extracellular levels
      of sLRP-1 can thus increase the half-life of TIMP-3 in the extracellular space,
      controlling the bioavailability of TIMP-3 to inhibit metalloproteinases.

PMID- 23166317
TI  - Compartmentalization and antiviral effect of efavirenz metabolites in blood
      plasma, seminal plasma, and cerebrospinal fluid.
AB  - Efavirenz (EFV) is one of the most commonly prescribed antiretrovirals for use in
      the treatment of human immunodeficiency virus (HIV) infection. EFV is extensively
      metabolized by cytochrome P450 to a number of oxygenated products; however, the
      pharmacologic activity and distribution of these metabolites in anatomic
      compartments have yet to be explored. The systemic distribution of EFV oxidative
      metabolites was examined in blood plasma, seminal plasma, and cerebrospinal fluid
      from subjects on an EFV-based regimen. The 8-hydroxy EFV metabolite was detected
      in blood plasma, seminal plasma, and cerebrospinal fluid, with median
      concentrations of 314.5 ng/ml, 358.5 ng/ml, and 3.37 ng/ml, respectively. In
      contrast, 7-hydroxy and 8,14-hydroxy EFV were only detected in blood plasma and
      seminal plasma with median concentrations of 8.84 ng/ml and 10.23 ng/ml, and 5.63
      ng/ml and 5.43 ng/ml, respectively. Interestingly, protein-free concentrations of
      metabolites were only detectable in seminal plasma, where a novel dihdyroxylated
      metabolite of EFV was also detected. This accumulation of protein-free EFV
      metabolites was demonstrated to be the result of differential protein binding in
      seminal plasma compared with that of blood plasma. In addition, the oxidative
      metabolites of EFV did not present with any significant pharmacologic activity
      toward HIV-1 as measured using an HIV green fluorescent protein single-round
      infectivity assay. This study is the first to report the physiologic distribution
      of metabolites of an antiretroviral into biologic compartments that the virus is
      known to distribute and to examine their anti-HIV activity. These data suggest
      that the male genital tract may be a novel compartment that should be considered
      in the evaluation of drug metabolite exposure.

PMID- 23166319
TI  - The role of UNC93B1 protein in surface localization of TLR3 receptor and in cell
      priming to nucleic acid agonists.
AB  - Translocation of nucleic acid-sensing (NAS) Toll-like receptors (TLRs) to
      endosomes is essential for response to microbial nucleic acids as well as for
      prevention of the autoimmune response. The accessory protein UNC93B1 is
      indispensable for activation of NAS TLRs because it regulates their response
      through trafficking to endosomes. We observed that poly(I:C) up-regulates
      transcription of UNC93B1 and promotes trafficking of TLR3 to the plasma membrane
      in human epithelial cell line. Up-regulation of UNC93B1 is triggered through TLR3
      activation by poly(I:C). Further studies revealed that expression of UNC93B1
      promotes trafficking of differentially glycosylated TLR3, but not other NAS TLRs,
      to the plasma membrane. UNC93B1 promoter region contains binding sites for
      poly(I:C)- and type I interferon-inducible regulatory elements. UNC93B1 also
      increases the protein lifetime of TLR3 and TLR9 and augments signaling of all NAS
      TLRs. Furthermore, we discovered that poly(I:C) pretreatment primes B-cells to
      the activation by ssDNA via up-regulation of UNC93B1. Our findings identified
      TLR3 as the important regulator of UNC93B1 that in turn governs the
      responsiveness of all NAS TLRs.

PMID- 23166320
TI  - Molecular interaction studies of HIV-1 matrix protein p17 and heparin:
      identification of the heparin-binding motif of p17 as a target for the
      development of multitarget antagonists.
AB  - Once released by HIV(+) cells, p17 binds heparan sulfate proteoglycans (HSPGs)
      and CXCR1 on leukocytes causing their dysfunction. By exploiting an approach
      integrating computational modeling, site-directed mutagenesis of p17, chemical
      desulfation of heparin, and surface plasmon resonance, we characterized the
      interaction of p17 with heparin, a HSPG structural analog, and CXCR1. p17 binds
      to heparin with an affinity (K(d) = 190 nm) that is similar to those of other
      heparin-binding viral proteins. Two stretches of basic amino acids (basic motifs)
      are present in p17 N and C termini. Neutralization (Arg->Ala substitution) of the
      N-terminal, but not of the C-terminal basic motif, causes the loss of p17 heparin
      binding capacity. The N-terminal heparin-binding motif of p17 partially overlaps
      the CXCR1-binding domain. Accordingly, its neutralization prevents also p17
      binding to the chemochine receptor. Competition experiments demonstrated that
      free heparin and heparan sulfate (HS), but not selectively 2-O-, 6-O-, and N-O
      desulfated heparins, prevent p17 binding to substrate-immobilized heparin,
      indicating that the sulfate groups of the glycosaminoglycan mediate p17
      interaction. Evaluation of the p17 antagonist activity of a panel of
      biotechnological heparins derived by chemical sulfation of the Escherichia coli
      K5 polysaccharide revealed that the highly N,O-sulfated derivative prevents the
      binding of p17 to both heparin and CXCR1, thus inhibiting p17-driven chemotactic
      migration of human monocytes with an efficiency that is higher than those of
      heparin and HS. Here, we characterized at a molecular level the interaction of
      p17 with its cellular receptors, laying the basis for the development of heparin
      mimicking p17 antagonists.

PMID- 23166321
TI  - Interaction between the elastin peptide VGVAPG and human elastin binding protein.
AB  - The elastin binding protein (EBP), a spliced variant of lysosomal beta
      galactosidase, is the primary receptor of elastin peptides that have been linked
      to emphysema, aneurysm and cancer progression. The sequences recognized by EBP
      share the XGXXPG consensus pattern found in numerous matrix proteins, notably in
      elastin where the VGVAPG motif is repeated. To delineate the elastin binding site
      of human EBP, we built a homology model of this protein and docked VGVAPG on its
      surface. Analysis of this model suggested that Gln-97 and Asp-98 were required
      for interaction with VGVAPG because they contribute to the definition of a pocket
      thought to represent the elastin binding site of EBP. Additionally, we proposed
      that Leu-103, Arg-107, and Glu-137 were essential residues because they could
      interact with VGVAPG itself. Site-directed mutagenesis experiments at these key
      positions validated our model. This work therefore provides the first structural
      data concerning the interaction of the VGVAPG with its cognate receptor. The
      present structural data should now allow the development of EBP-specific
      antagonists.

PMID- 23166322
TI  - Laminin network formation studied by reconstitution of ternary nodes in solution.
AB  - The polymerization of laminins into a cell-associated network is a key process in
      basement membrane assembly. Network formation is mediated by the homologous short
      arm tips of the laminin heterotrimer, each consisting of a globular laminin N
      terminal (LN) domain followed by a tandem of laminin-type epidermal growth factor
      like (LEa) domains. How the short arms interact in the laminin network is
      unclear. Here, we have addressed this question by reconstituting laminin network
      nodes in solution and analyzing them by size exclusion chromatography and light
      scattering. Recombinant LN-LEa1-4 fragments of the laminin alpha1, alpha2,
      alpha5, beta1, and gamma1 chains were monomeric in solution. The beta1 and gamma1
      fragments formed the only detectable binary complex and ternary complexes of
      1:1:1 stoichiometry with all alpha chain fragments. Ternary complex formation
      required calcium and did not occur at 4  degrees C, like the polymerization of
      full-length laminins. Experiments with chimeric short arm fragments demonstrated
      that the LEa2-4 regions of the beta1 and gamma1 fragments are dispensable for
      ternary complex formation, and an engineered glycan in the beta1 LEa1 domain was
      also tolerated. In contrast, mutation of Ser-68 in the beta1 LN domain
      (corresponding to a Pierson syndrome mutation in the closely related beta2 chain)
      abolished ternary complex formation. We conclude that authentic ternary nodes of
      the laminin network can be reconstituted for structure-function studies.

PMID- 23166323
TI  - Nuclear factor of activated T-cells (NFAT)C2 inhibits Notch receptor signaling in
      osteoblasts.
AB  - Notch receptors regulate osteoblastogenesis, and Notch activation induces
      cleavage and nuclear translocation of the Notch intracellular domain (NICD),
      which associates with Epstein-Barr virus latency C-promoter binding factor
      1/suppressor of hairless/lag-1 (CSL) and induces transcription of Notch target
      genes, such as hairy enhancer of split-related with YRPW motif (Hey)1 and Hey2.
      Nuclear factors of activated T-cells (NFAT) are transcription factors that
      regulate osteoclastogenesis, but their function in osteoblasts is not clear.
      Notch inhibits NFATc1 transcription, but interactions between Notch and NFAT are
      understood poorly. To determine the regulation of NFAT expression by Notch,
      osteoblasts from Rosa(Notch) mice, where NICD is transcribed following excision
      of a loxP flanked STOP cassette, were used. Alternatively, wild-type C57BL/6
      osteoblasts were exposed to the Notch ligand Delta-like (Dll)1 to induce Notch
      signaling or to bovine serum albumin as control. In Rosa(Notch) osteoblasts,
      Notch suppressed NFATc1 expression, increased Nfatc2 mRNA by post-transcriptional
      mechanisms, and had no effect on NFATc3 and NFATc4 transcripts. Induction of
      Nfatc2 transcripts by Notch was confirmed in C57BL/6 osteoblasts exposed to Dll1.
      To investigate NFATc2 function in osteoblasts, constitutively active NFATc2 was
      overexpressed in Rosa(Notch) osteoblasts. NFATc2 suppressed Notch transactivation
      and expression of Hey genes. Electrophoretic mobility shift assays revealed that
      NFATc2 and CSL bind to similar DNA sequences, and chromatin immunoprecipitation
      indicated that NFATc2 displaced CSL from the Hey2 promoter. The effects of NICD
      and NFATc2 in Rosa(Notch) osteoblasts were assessed, and both proteins inhibited
      osteoblast function. In conclusion, Notch stabilizes Nfatc2 transcripts, NFATc2
      suppresses Notch signaling, and both proteins inhibit osteoblast function.

PMID- 23166324
TI  - Irreversible heavy chain transfer to hyaluronan oligosaccharides by tumor
      necrosis factor-stimulated gene-6.
AB  - The covalent transfer of heavy chains (HCs) from inter-alpha-inhibitor (IalphaI)
      to hyaluronan (HA) via the protein product of tumor necrosis factor-stimulated
      gene-6 (TSG-6) forms the HC-HA complex, a pathological form of HA that promotes
      the adhesion of leukocytes to HA matrices. The transfer of HCs to high molecular
      weight (HMW) HA is a reversible event whereby TSG-6 can shuffle HCs from one HA
      molecule to another. Therefore, HMW HA can serve as both an HC acceptor and an HC
      donor. In the present study, we show that transfer of HCs to low molecular weight
      HA oligosaccharides is an irreversible event where subsequent shuffling does not
      occur, i.e. HA oligosaccharides from 8 to 21 monosaccharide units in length can
      serve as HC acceptors, but are unable to function as HC donors. We show that the
      HC-HA complex is present in the synovial fluid of mice subjected to systemic and
      monoarticular mouse models of rheumatoid arthritis. Furthermore, we demonstrate
      that HA oligosaccharides can be used, with TSG-6, to irreversibly shuffle HCs
      from pathological, HMW HC-HA to HA oligosaccharides, thereby restoring HC-HA
      matrices from the inflamed joint to their normal state, unmodified with HCs. This
      process was also effective for HC-HA in the synovial fluid of human rheumatoid
      arthritis patients (in vitro).

PMID- 23166325
TI  - Distinct roles in autophagy and importance in infectivity of the two ATG4
      cysteine peptidases of Leishmania major.
AB  - Macroautophagy in Leishmania, which is important for the cellular remodeling
      required during differentiation, relies upon the hydrolytic activity of two ATG4
      cysteine peptidases (ATG4.1 and ATG4.2). We have investigated the individual
      contributions of each ATG4 to Leishmania major by generating individual gene
      deletion mutants (Deltaatg4.1 and Deltaatg4.2); double mutants could not be
      generated, indicating that ATG4 activity is required for parasite viability. Both
      mutants were viable as promastigotes and infected macrophages in vitro and mice,
      but Deltaatg4.2 survived poorly irrespective of infection with promastigotes or
      amastigotes, whereas this was the case only when promastigotes of Deltaatg4.1
      were used. Promastigotes of Deltaatg4.2 but not Deltaatg4.1 were more susceptible
      than wild type promastigotes to starvation and oxidative stresses, which
      correlated with increased reactive oxygen species levels and oxidatively damaged
      proteins in the cells as well as impaired mitochondrial function. The antioxidant
      N-acetylcysteine reversed this phenotype, reducing both basal and induced
      autophagy and restoring mitochondrial function, indicating a relationship between
      reactive oxygen species levels and autophagy. Deletion of ATG4.2 had a more
      dramatic effect upon autophagy than did deletion of ATG4.1. This phenotype is
      consistent with a reduced efficiency in the autophagic process in Deltaatg4.2,
      possibly due to ATG4.2 having a key role in removal of ATG8 from mature
      autophagosomes and thus facilitating delivery to the lysosomal network. These
      findings show that there is a level of functional redundancy between the two
      ATG4s, and that ATG4.2 appears to be the more important. Moreover, the low
      infectivity of Deltaatg4.2 demonstrates that autophagy is important for the
      virulence of the parasite.

PMID- 23166326
TI  - Biochemical characterization of individual human glycosylated pro-insulin-like
      growth factor (IGF)-II and big-IGF-II isoforms associated with cancer.
AB  - Insulin-like growth factor II (IGF-II) is a major embryonic growth factor
      belonging to the insulin-like growth factor family, which includes insulin and
      IGF-I. Its expression in humans is tightly controlled by maternal imprinting, a
      genetic restraint that is lost in many cancers, resulting in up-regulation of
      both mature IGF-II mRNA and protein expression. Additionally, increased
      expression of several longer isoforms of IGF-II, termed "pro" and "big" IGF-II,
      has been observed. To date, it is ambiguous as to what role these IGF-II isoforms
      have in initiating and sustaining tumorigenesis and whether they are
      bioavailable. We have expressed each individual IGF-II isoform in their proper O
      glycosylated format and established that all bind to the IGF-I receptor and both
      insulin receptors A and B, resulting in their activation and subsequent
      stimulation of fibroblast proliferation. We also confirmed that all isoforms are
      able to be sequestered into binary complexes with several IGF-binding proteins
      (IGFBP-2, IGFBP-3, and IGFBP-5). In contrast to this, ternary complex formation
      with IGFBP-3 or IGFBP-5 and the auxillary protein, acid labile subunit, was
      severely diminished. Furthermore, big-IGF-II isoforms bound much more weakly to
      purified ectodomain of the natural IGF-II scavenging receptor, IGF-IIR. IGF-II
      isoforms thus possess unique biological properties that may enable them to escape
      normal sequestration avenues and remain bioavailable in vivo to sustain oncogenic
      signaling.

PMID- 23166327
TI  - Oncogenic microRNA-155 down-regulates tumor suppressor CDC73 and promotes oral
      squamous cell carcinoma cell proliferation: implications for cancer therapeutics.
AB  - The CDC73 gene is mutationally inactivated in hereditary and sporadic parathyroid
      tumors. It negatively regulates beta-catenin, cyclin D1, and c-MYC. Down
      regulation of CDC73 has been reported in breast, renal, and gastric carcinomas.
      However, the reports regarding the role of CDC73 in oral squamous cell carcinoma
      (OSCC) are lacking. In this study we show that CDC73 is down-regulated in a
      majority of OSCC samples. We further show that oncogenic microRNA-155 (miR-155)
      negatively regulates CDC73 expression. Our experiments show that the dramatic up
      regulation of miR-155 is an exclusive mechanism for down-regulation of CDC73 in a
      panel of human cell lines and a subset of OSCC patient samples in the absence of
      loss of heterozygosity, mutations, and promoter methylation. Ectopic expression
      of miR-155 in HEK293 cells dramatically reduced CDC73 levels, enhanced cell
      viability, and decreased apoptosis. Conversely, the delivery of a miR-155
      antagonist (antagomir-155) to KB cells overexpressing miR-155 resulted in
      increased CDC73 levels, decreased cell viability, increased apoptosis, and marked
      regression of xenografts in nude mice. Cotransfection of miR-155 with CDC73 in
      HEK293 cells abrogated its pro-oncogenic effect. Reduced cell proliferation and
      increased apoptosis of KB cells were dependent on the presence or absence of the
      3'-UTR in CDC73. In summary, knockdown of CDC73 expression due to overexpression
      of miR-155 not only adds a novelty to the list of mechanisms responsible for its
      down-regulation in different tumors, but the restoration of CDC73 levels by the
      use of antagomir-155 may also have an important role in therapeutic intervention
      of cancers, including OSCC.

PMID- 23166328
TI  - Cytokine response is determined by duration of receptor and signal transducers
      and activators of transcription 3 (STAT3) activation.
AB  - Paradoxically, the pro-inflammatory cytokine IL-6 and the anti-inflammatory
      cytokine IL-10 both activate STAT3, yet generate nearly opposing cellular
      responses. Here, we show that the temporal pattern of STAT3 activation codes for
      the specific cytokine response. A computational model of IL-6 and IL-10 signaling
      predicted that IL-6 stimulation results in transient activation of STAT3, with a
      rapid decline in phosphorylation and nuclear localization. In contrast, simulated
      IL-10 signaling resulted in sustained STAT3 activation. The predicted STAT3
      patterns produced by each cytokine were confirmed experimentally in human
      dendritic cells. Time course microarray studies further showed that the dynamic
      genome-wide transcriptional responses were nearly identical at early time points
      following stimulation (when STAT3 is active in response to both IL-6 and IL-10)
      but divergent at later times (when STAT3 is active only in response to IL-10).
      Truncating STAT3 activation after IL-10 stimulation caused IL-10 to elicit an IL
      6-like transcriptional and secretory response. That the duration of IL-10
      receptor and STAT3 activation can direct distinct responses reveals a complex
      cellular information-coding mechanism that may be relevant to improving the
      prediction of the effects of drug candidates using this mechanism.

PMID- 23166329
TI  - Neurokinin-1 receptor directly mediates glioma cell migration by up-regulation of
      matrix metalloproteinase-2 (MMP-2) and membrane type 1-matrix metalloproteinase
      (MT1-MMP).
AB  - Neurokinin-1 receptor (NK1R) occurs naturally on human glioblastomas. Its
      activation mediates glioma cell proliferation. However, it is unknown whether
      NK1R is directly involved in tumor cell migration. In this study, we found human
      hemokinin-1 (hHK-1), via NK1R, dose-dependently promoted the migration of U-251
      and U-87 cells. In addition, we showed that hHK-1 enhanced the activity of MMP-2
      and the expression of MMP-2 and MT1-matrix metalloproteinase (MMP), which were
      responsible for cell migration, because neutralizing the MMPs with antibodies
      decreased cell migration. The involved mechanisms were then investigated. In U
      251, hHK-1 induced significant calcium efflux; phospholipase C inhibitor U-73122
      reduced the calcium mobilization, the up-regulation of MMP-2 and MT1-MMP, and the
      cell migration induced by hHK-1, which meant the migration effect of NK1R was
      mainly mediated through the G(q)-PLC pathway. We further demonstrated that hHK-1
      boosted rapid phosphorylation of ERK, JNK, and Akt; inhibition of ERK and Akt
      effectively reduced MMP-2 induction by hHK-1. Meanwhile, inhibition of ERK, JNK,
      and Akt reduced the MT1-MMP induction. hHK-1 stimulated significant
      phosphorylation of p65 and c-JUN in U-251. Reporter gene assays indicated hHK-1
      enhanced both AP-1 and NF-kappaB activity; inhibition of ERK, JNK, and Akt dose
      dependently suppressed the NF-kappaB activity; only the inhibition of ERK
      significantly suppressed the AP-1 activity. Treatment with specific inhibitors
      for AP-1 or NF-kappaB strongly blocked the MMP up-regulation by hHK-1. Taken
      together, our data suggested NK1R was a potential regulator of human glioma cell
      migration by the up-regulation of MMP-2 and MT1-MMP.

PMID- 23166331
TI  - The United States Children's Bureau and pediatric medicine: a retrospective
      analysis.

PMID- 23166330
TI  - Functional expression of SCL/TAL1 interrupting locus (Stil) protects retinal
      dopaminergic cells from neurotoxin-induced degeneration.
AB  - We previously isolated a dominant mutation, night blindness b (nbb), which causes
      a late onset of retinal dopaminergic cell degeneration in zebrafish. In this
      study, we cloned the zebrafish nbb locus. Sequencing results revealed that nbb is
      a homolog of the vertebrate SCL/TAL1 interrupting locus (Stil). The Stil gene has
      been shown to play important roles in the regulation of vertebrate embryonic
      neural development and human cancer cell proliferation. In this study, we
      demonstrate that functional expression of Stil is also required for neural
      survival. In zebrafish, decreased expression of Stil resulted in increased toxic
      susceptibility of retinal dopaminergic cells to 6-hydroxydopamine. Increases in
      Stil-mediated Shh signaling transduction (i.e. by knocking down the Shh repressor
      Sufu) prevented dopaminergic cell death induced by neurotoxic insult. The data
      suggest that the oncogene Stil also plays important roles in neural protection.

PMID- 23166332
TI  - Evisceration of small bowel after cauterization of an umbilical mass.
AB  - The omphalomesenteric duct (OMD), a temporary structure essential to fetal
      development, normally involutes completely by week 8 or 9 of gestation. On
      occasion, the OMD persists, the clinical presentations of which vary widely. We
      describe a case of a 6-week-old male with a patent OMD remnant that was initially
      treated as an umbilical granuloma, which then potentially allowed for prolapse of
      the small bowel through the umbilical ring. The patient required resection of the
      incarcerated bowel but had an otherwise uneventful and complete recovery.

PMID- 23166333
TI  - Muscle-enhancing behaviors among adolescent girls and boys.
AB  - OBJECTIVE: Media images of men and women have become increasingly muscular, and
      muscle-enhancing techniques are available to youth. Identifying populations at
      risk for unhealthy muscle-enhancingbehaviors is of considerable public health
      importance. The current study uses a large and diverse population-based sample of
      adolescents to examine the prevalence of muscle-enhancing behaviors and
      differences across demographic characteristics, weight status, and sports team
      involvement. METHODS: Survey data from 2793 diverse adolescents (mean age = 14.4)
      were collected at 20 urban middle and high schools. Use of 5 muscle-enhancing
      behaviors was assessed (changing eating, exercising, protein powders, steroids
      and other muscle-enhancing substances), and a summary score reflecting use of 3
      or more behaviors was created. Logistic regression was used to test for
      differences in each behavior across age group, race/ethnicity, socioeconomic
      status, BMI category, and sports team participation. RESULTS: Muscle-enhancing
      behaviors were common in this sample for both boys and girls. For example, 34.7%
      used protein powders or shakes and 5.9% reported steroid use. Most behaviors were
      significantly more common among boys. In models mutually adjusted for all
      covariates, grade level, Asian race, BMI category, and sports team participation
      were significantly associated with the use of muscle-enhancing behaviors. For
      example, overweight (odds ratio = 1.45) and obese (odds ratio = 1.90) girls had
      significantly greater odds of using protein powders or shakes than girls of
      average BMI. CONCLUSIONS: The use of muscle-enhancing behaviors is substantially
      higher than has been previously reported and is cause for concern. Pediatricians
      and other health care providers should ask their adolescent patients about muscle
      enhancing behaviors.

PMID- 23166335
TI  - Pediatricians' use of health information technology: a national survey.
AB  - BACKGROUND AND OBJECTIVE: There are limited national data on pediatric health
      information technology adoption rates. Our objective was to determine
      pediatricians' adoption rates of electronic health record systems (EHRs),
      barriers to adoption, and features of the systems adopted. METHODS: A survey of
      1620 randomly selected US members of the American Academy of Pediatrics from
      February to July 2009 addressed use of EHRs and barriers to adoption. Bivariate
      analysis and logistic regression were used to determine associations between EHR
      use and various physician and practice characteristics. RESULTS: Six hundred
      forty-six postresidency pediatric clinicians practicing in office- or clinic
      based settings responded (57.2%). Self-reported electronic medical record/EHR use
      was 54%/41%, but far fewer used systems that met the definition of a basic (25%)
      or fully functional (6%) EHR. Only 3% used a system that was fully functional and
      pediatric-supportive. Pediatricians practicing in multispecialty practices and
      those in hospital-based practices were more likely to use basic or fully
      functional EHRs than those in solo/2-physician practices. More than half of
      respondents reported financial barriers to implementing EHRs, and more than one
      third were concerned about whether systems could meet their needs and whether an
      EHR would affect productivity. CONCLUSIONS: Pediatric adoption of fully
      functional EHRs lags general adoption. Barriers to adoption include financial and
      productivity concerns, but pediatricians are also concerned about finding systems
      that meet their needs. Few pediatricians use a system that is pediatric
      supportive. To help identify pediatric-supportive systems, EHR certification
      efforts should include these requirements.

PMID- 23166334
TI  - Single ABCA3 mutations increase risk for neonatal respiratory distress syndrome.
AB  - BACKGROUND AND OBJECTIVE: Neonatal respiratory distress syndrome (RDS) due to
      pulmonary surfactant deficiency is heritable, but common variants do not fully
      explain disease heritability. METHODS: Using next-generation, pooled sequencing
      of race-stratified DNA samples from infants >=34 weeks' gestation with and
      without RDS (n = 513) and from a Missouri population-based cohort (n = 1066), we
      scanned all exons of 5 surfactant-associated genes and used in silico algorithms
      to identify functional mutations. We validated each mutation with an independent
      genotyping platform and compared race-stratified, collapsed frequencies of rare
      mutations by gene to investigate disease associations and estimate attributable
      risk. RESULTS: Single ABCA3 mutations were overrepresented among European-descent
      RDS infants (14.3% of RDS vs 3.7% of non-RDS; P = .002) but were not
      statistically overrepresented among African-descent RDS infants (4.5% of RDS vs
      1.5% of non-RDS; P = .23). In the Missouri population-based cohort, 3.6% of
      European-descent and 1.5% of African-descent infants carried a single ABCA3
      mutation. We found no mutations among the RDS infants and no evidence of
      contribution to population-based disease burden for SFTPC, CHPT1, LPCAT1, or
      PCYT1B. CONCLUSIONS: In contrast to lethal neonatal RDS resulting from homozygous
      or compound heterozygous ABCA3 mutations, single ABCA3 mutations are
      overrepresented among European-descent infants >=34 weeks' gestation with RDS and
      account for ~10.9% of the attributable risk among term and late preterm infants.
      Although ABCA3 mutations are individually rare, they are collectively common
      among European- and African-descent individuals in the general population.

PMID- 23166336
TI  - Neurodevelopmental burden at age 5 years in patients with univentricular heart.
AB  - BACKGROUND: Despite increasing survival, patients with hypoplastic left heart
      syndrome (HLHS) and other forms of functionally univentricular heart defects
      (UVHs) remain at increased risk of long-term neurodevelopmental deficits.
      METHODS: A nationwide sample of 23 patients with HLHS, 13 with UVH, and 40
      controls were followed prospectively until the age of 5 years, when neurologic,
      neuropsychological, and motor examinations and brain MRI were performed. RESULTS:
      The median full-scale IQ was significantly lower in patients with HLHS (97, P <
      .001) and patients with UVH (112, P = .024) compared with controls (121). Major
      neurodevelopmental impairment was found in 26% of the patients with HLHS and 23%
      of those with UVH, and minor neurologic dysfunction was found in 43% and 46%,
      respectively. MRI revealed abnormalities, mostly ischemic changes of different
      degrees, in 82% of the patients with HLHS and in 56% of those with UVH. Prominent
      changes were significantly associated with neurodevelopmental findings and
      parental reports of adaptive behavior. In linear regression, significant risk
      factors for a worse outcome were a history of clinical seizures in connection
      with the primary operation, a lower diameter of the neonatal ascending aorta, and
      several pre-, peri-, and postoperative factors related to the primary and
      bidirectional Glenn operations. CONCLUSIONS: Although median cognitive
      performance was within the normal range, neurodevelopmental and brain MRI
      abnormalities were found in the majority of the patients with UVH, and especially
      in those with HLHS, at preschool age. Both a narrowed ascending aorta and
      operation-related factors contributed to these findings.

PMID- 23166337
TI  - Health care provider and caregiver preferences regarding nasogastric and
      intravenous rehydration.
AB  - OBJECTIVE: Despite evidence supporting its use, nasogastric rehydration is rarely
      used in North America. We conducted a prospective, cross-sectional, 3-phase study
      to evaluate current perspectives. METHODS: We compared the proportions of
      respondents in favor of nasogastric (as opposed to intravenous) rehydration,
      should oral rehydration fail, between clinicians and caregivers. Phase 1:
      caregivers of children aged 3 to 48 months, who presented to a Canadian pediatric
      emergency department with symptoms of gastroenteritis, were invited to complete a
      survey. Phase 2: phase 1 participants administered intravenous or nasogastric
      rehydration had the procedure observed and outcome data recorded. Phase 3:
      pediatric emergency medicine physicians, fellows, and nurses completed a survey.
      RESULTS: Four hundred thirty-five children-parent dyads and 113 health care
      providers participated. If oral rehydration were to fail, 10% (47 of 435) of
      caregivers and 14% (16 of 113) of clinicians would choose nasogastric rehydration
      (difference = 3.4%; 95% confidence interval: -2.8 to 11.4). Caregivers were more
      familiar with the term intravenous than nasogastric rehydration (80% vs 20%; P <
      .001). Sixty-four children (15%) received intravenous rehydration; none received
      nasogastric rehydration. Participating nurses have inserted 90 (interquartile
      range: 25-150) intravenous cannulas compared with 4 (interquartile range: 2-10)
      nasogastric tubes during the preceding 6 months (P < .001). After a brief
      educational intervention, the proportion recommending nasogastric rehydration
      increased to 27% (117 of 435) among caregivers (P < .001) and 43% (49 of 113)
      among health care providers (P < .001). CONCLUSIONS: In keeping with caregiver
      desires, health care providers in a Canadian emergency department employ
      intravenous rehydration when oral rehydration fails. Enhanced change management
      strategies will be required for nasogastric rehydration to become adopted in this
      environment.

PMID- 23166338
TI  - Cerebral palsy and neonatal death in term singletons born small for gestational
      age.
AB  - BACKGROUND AND OBJECTIVES: To investigate the probable timing of events leading
      to cerebral palsy (CP) in singletons born small for gestational age (SGA) at
      term, taking neonatal death into consideration. METHODS: In this registry-based
      cohort study, data on 400 488 singletons born during 1996-2003 were abstracted
      from the Medical Birth and the CP registries of Norway. Among 36 604 SGA children
      (birth weight <10th percentile), 104 died in the neonatal period and 69 developed
      CP. Apgar scores at 5 minutes, risk factors, MRI findings, and CP subtypes were
      used to assess the timing of events leading to CP or neonatal death. RESULTS:
      Intrapartum origin of CP was considered in 5 SGA children (7%; 95% confidence
      interval: 3-16) in comparison with 31 of 263 (12%; 95% confidence interval: 8-16)
      non-SGA children (P = .28). The proportions of children who died in the neonatal
      period after a probable intrapartum event did not differ between the groups when
      children with congenital malformations were excluded. Probable antenatal events
      leading to CP and neonatal death were more common among SGA than non-SGA children
      (P < .001). CONCLUSIONS: In ~90% of children born SGA the event leading to CP is
      of probable antenatal origin. The low proportion of SGA children with CP after a
      probable intrapartum event was not outweighed by a higher neonatal mortality rate
      when congenital malformations were excluded. The higher risk of CP among SGA than
      among non-SGA children is probably due to a higher prevalence of antenatal risk
      factors.

PMID- 23166339
TI  - Prevalence and characteristics of rib fractures in ex-preterm infants.
AB  - OBJECTIVES: This study aimed to identify the prevalence and characteristics of
      rib fractures in ex-preterm infants. METHODS: Infants born at <37 weeks'
      gestation and admitted before 2011 to 3 regional neonatal units were identified
      from admission registers. For 2 centers, these data were available from 2000
      onward and, for another center, from 2005. Electronic records were searched to
      identify chest radiographs performed up to age 1 year. Chest radiograph reports
      were then reviewed for evidence of rib fractures, and the case notes of all
      affected individuals were scrutinized. RESULTS: Of the 3318 eligible preterm
      infants, 1446 had a total of 9386 chest radiographs. Of these infants, 26 (1.8%)
      were identified as having a total of 62 rib fractures. Their median (range)
      gestation at birth was 26 weeks (23-34). The median chronological age of these
      infants at the time of the radiograph was 14 weeks (5 weeks to 8 months). The
      median corrected gestational age at the time of the radiograph was 39 weeks (34
      weeks to 4 months). Of the 62 fractures, 27 (36%) were sited posteriorly, and 15
      (53%) of the infants with posterior rib fractures were diagnosed with osteopathy
      of prematurity. Classic risk including conjugated hyperbilirubinemia and
      diuretics, were present in 23 of 26 (88%) infants. A full skeletal survey was
      performed in 8 of 26 (31%). Investigations for nonaccidental injury occurred in 4
      of 26 (15%) cases. CONCLUSIONS: Evidence of rib fractures is present in ~2% of ex
      preterm infants. The evaluation of these fractures in infancy requires a detailed
      neonatal history irrespective of the site of rib fracture.

PMID- 23166340
TI  - Age, academic performance, and stimulant prescribing for ADHD: a nationwide
      cohort study.
AB  - BACKGROUND: We evaluated whether younger age in class is associated with poorer
      academic performance and an increased risk of being prescribed stimulants for
      attention-deficit/hyperactivity disorder (ADHD). METHODS: This was a nationwide
      population-based cohort study, linking data from national registries of
      prescribed drugs and standardized scholastic examinations. The study population
      comprised all children born in 1994-1996 who took standardized tests in Iceland
      at ages 9 and 12 (n = 11 785). We estimated risks of receiving low test scores (0
      10th percentile) and being prescribed stimulants for ADHD. Comparisons were made
      according to children's relative age in class. RESULTS: Mean test scores in
      mathematics and language arts were lowest among the youngest children in the
      fourth grade, although the gap attenuated in the seventh grade. Compared with the
      oldest third, those in the youngest third of class had an increased relative risk
      of receiving a low test score at age 9 for mathematics (1.9; 95% confidence
      interval [CI] 1.6-2.2) and language arts (1.8; 95% CI 1.6-2.1), whereas at age
      12, the relative risk was 1.6 in both subjects. Children in the youngest third of
      class were 50% more likely (1.5; 95% CI 1.3-1.8) than those in the oldest third
      to be prescribed stimulants between ages 7 and 14. CONCLUSIONS: Relative age
      among classmates affects children's academic performance into puberty, as well as
      their risk of being prescribed stimulants for ADHD. This should be taken into
      account when evaluating children's performance and behavior in school to prevent
      unnecessary stimulant treatment.

PMID- 23166341
TI  - Long-term complications of therapeutic exposures in childhood: lessons learned
      from childhood cancer survivors.

PMID- 23166342
TI  - Predictors of persistence after a positive depression screen among adolescents.
AB  - OBJECTIVE: To examine predictors of depression persistence after a positive
      screening test to inform management protocols for screened youth. METHODS: We
      conducted a cohort study of 444 youth (aged 13-17 years) from a large health care
      delivery system. Youth with depressive symptoms, based on a 2-item depression
      screen, were oversampled for the baseline interview. Baseline assessments
      included the Patient Health Questionnaire 9-item (PHQ-9) depression screen as
      well as clinical factors that were hypothesized to influence depression
      persistence (family history of depression, functional impairment, perceived
      social support, anxiety symptoms, externalizing symptoms, and medical
      comorbidity). Logistic regression analysis was used to examine factors associated
      with the persistence of depression at 6 months postbaseline. RESULTS: Of 113
      youth with a positive baseline screen (PHQ-9 >=11), 47% and 35% continued to be
      positive at 6-week and 6-month follow-up, respectively. After controlling for
      treatment status, only 2 factors were significantly associated with depression
      persistence at 6 months: baseline depressive symptom score and continuing to have
      a positive screen at 6 weeks. For each 1-point increase on the PHQ-9 score at
      baseline, youth had a 16% increased odds of continuing to be depressed at 6
      months (odds ratio: 1.16, 95% confidence interval: 1.01-1.34). Youth who
      continued to screen positive 6 weeks later had almost 3 times the odds of being
      depressed at 6 months (odds ratio: 2.89, 95% confidence interval: 1.09-7.61).
      CONCLUSIONS: Depressive symptom severity at presentation and continued symptoms
      at 6 weeks postscreening are the strongest predictors of depression persistence.
      Patients with high depressive symptom scores and continued symptoms at 6 weeks
      should receive active treatment.

PMID- 23166344
TI  - Vaccination coverage among American Indian and Alaska native children, 2006-2010.
AB  - BACKGROUND AND OBJECTIVES: A previous study on vaccination coverage in the
      American Indian/Alaska Native (AI/AN) population found that disparities in
      coverage between AI/AN and white children existed from 2001 to 2004 but were
      absent in 2005. The objective of this study was to describe vaccination coverage
      levels for AI/AN children aged 19-35 months in the United States between 2006 and
      2010, examining whether gains found for AI/AN children in 2005 have been
      sustained. METHODS: Data from the 2006 through 2010 National Immunization Surveys
      were analyzed. Groups were defined as AI/AN (alone or in combination with any
      other race and excluding Hispanics) and white-only non-Hispanic children.
      Comparisons in demographics and vaccination coverage were made. RESULTS:
      Demographic risk factors often associated with underimmunization were
      significantly higher for AI/AN respondents compared with white respondents in
      most years studied. Overall, vaccination coverage was similar between the 2
      groups in most years, although coverage with 4 or more doses of pneumococcal
      conjugate vaccine was lower for AI/AN children in 2008 and 2009, as was coverage
      with vaccine series measures the series in 2006 and 2009. When stratified by
      geographic regions, AI/AN children had coverage that was similar to or higher
      than that of white children for most vaccines in most years studied. CONCLUSIONS:
      The gains in vaccination coverage found in 2005 have been maintained. The absence
      of disparities in coverage with most vaccines between AI/AN children and white
      children from 2006 through 2010 is a clear success. These types of periodic
      reviews are important to ensure we remain vigilant.

PMID- 23166343
TI  - Continuous Versus Bolus Infusion of Doxorubicin in Children With ALL: Long-term
      Cardiac Outcomes.
AB  - BACKGROUND AND OBJECTIVES: Doxorubicin, effective against many malignancies, is
      limited by cardiotoxicity. Continuous-infusion doxorubicin, compared with bolus
      infusion, reduces early cardiotoxicity in adults. Its effectiveness in reducing
      late cardiotoxicity in children remains uncertain. We determined continuous
      infusion doxorubicin cardioprotective efficacy in long-term survivors of
      childhood acute lymphoblastic leukemia (ALL). METHODS: The Dana-Farber Cancer
      Institute ALL Consortium Protocol 91-01 enrolled pediatric patients between 1991
      and 1995. Newly diagnosed high-risk patients were randomly assigned to receive a
      total of 360 mg/m(2) of doxorubicin in 30 mg/m(2) doses every 3 weeks, by either
      continuous (over 48 hours) or bolus-infusion (within 15 minutes). Echocardiograms
      at baseline, during, and after doxorubicin therapy were blindly remeasured
      centrally. Primary outcomes were late left ventricular (LV) structure and
      function. RESULTS: A total of 102 children were randomized to each treatment
      group. We analyzed 484 serial echocardiograms from 92 patients (n = 49
      continuous; n = 43 bolus) with >=1 echocardiogram >=3 years after assignment.
      Both groups had similar demographics and normal baseline LV characteristics.
      Cardiac follow-up after randomization (median, 8 years) showed changes from
      baseline within the randomized groups (depressed systolic function, systolic
      dilation, reduced wall thickness, and reduced mass) at 3, 6, and 8 years; there
      were no statistically significant differences between randomized groups. Ten-year
      ALL event-free survival rates did not differ between the 2 groups (continuous
      infusion, 83% versus bolus-infusion, 78%; P = .24). CONCLUSIONS: In survivors of
      childhood high-risk ALL, continuous-infusion doxorubicin, compared with bolus
      infusion, provided no long-term cardioprotection or improvement in ALL event-free
      survival, hence provided no benefit over bolus-infusion.

PMID- 23166345
TI  - Applying deep DNA sequencing to common, complex pediatric traits.

PMID- 23166347
TI  - We are still waiting for fully supportive electronic health records in
      pediatrics.

PMID- 23166346
TI  - Effectiveness of lifestyle interventions in child obesity: systematic review with
      meta-analysis.
AB  - BACKGROUND AND OBJECTIVES: The effects of lifestyle interventions on cardio
      metabolic outcomes in overweight children have not been reviewed systematically.
      The objective of the study was to examine the impact of lifestyle interventions
      incorporating a dietary component on both weight change and cardio-metabolic
      risks in overweight/obese children. METHODS: English-language articles from 1975
      to 2010, available from 7 databases, were used as data sources. Two independent
      reviewers assessed articles against the following eligibility criteria:
      randomized controlled trial, participants overweight/obese and <=18 years,
      comparing lifestyle interventions to no treatment/wait-list control, usual care,
      or written education materials. Study quality was critically appraised by 2
      reviewers using established criteria; Review Manager 5.1 was used for meta
      analyses. RESULTS: Of 38 eligible studies, 33 had complete data for meta-analysis
      on weight change; 15 reported serum lipids, fasting insulin, or blood pressure.
      Lifestyle interventions produced significant weight loss compared with no
      treatment control conditions: BMI (-1.25kg/m(2), 95% confidence interval [CI] 
      2.18 to -0.32) and BMI z score (-0.10, 95% CI -0.18 to -0.02). Studies comparing
      lifestyle interventions to usual care also resulted in significant immediate (
      1.30kg/m(2), 95% CI -1.58 to -1.03) and posttreatment effects (-0.92 kg/m(2), 95%
      CI -1.31 to -0.54) on BMI up to 1 year from baseline. Lifestyle interventions led
      to significant improvements in low-density lipoprotein cholesterol (-0.30 mmol/L,
      95% CI -0.45 to -0.15), triglycerides (-0.15 mmol/L, 95% CI -0.24 to -0.07),
      fasting insulin (-55.1 pmol/L, 95% CI -71.2 to -39.1) and blood pressure up to 1
      year from baseline. No differences were found for high-density lipoprotein
      cholesterol. CONCLUSIONS: Lifestyle interventions can lead to improvements in
      weight and cardio-metabolic outcomes. Further research is needed to determine the
      optimal length, intensity, and long-term effectiveness of lifestyle
      interventions.

PMID- 23166348
TI  - Mutual antagonism between IP(3)RII and miRNA-133a regulates calcium signals and
      cardiac hypertrophy.
AB  - Inositol 1,4,5'-triphosphate receptor II (IP(3)RII) calcium channel expression is
      increased in both hypertrophic failing human myocardium and experimentally
      induced models of the disease. The ectopic calcium released from these receptors
      induces pro-hypertrophic gene expression and may promote arrhythmias. Here, we
      show that IP(3)RII expression was constitutively restrained by the muscle
      specific miRNA, miR-133a. During the hypertrophic response to pressure overload
      or neurohormonal stimuli, miR-133a down-regulation permitted IP(3)RII levels to
      increase, instigating pro-hypertrophic calcium signaling and concomitant
      pathological remodeling. Using a combination of in vivo and in vitro approaches,
      we demonstrated that IP(3)-induced calcium release (IICR) initiated the
      hypertrophy-associated decrease in miR-133a. In this manner, hypertrophic stimuli
      that engage IICR set a feed-forward mechanism in motion whereby IICR decreased
      miR-133a expression, further augmenting IP(3)RII levels and therefore pro
      hypertrophic calcium release. Consequently, IICR can be considered as both an
      initiating event and a driving force for pathological remodeling.

PMID- 23166349
TI  - Csi1 links centromeres to the nuclear envelope for centromere clustering.
AB  - In the fission yeast Schizosaccharomyces pombe, the centromeres of each
      chromosome are clustered together and attached to the nuclear envelope near the
      site of the spindle pole body during interphase. The mechanism and functional
      importance of this arrangement of chromosomes are poorly understood. In this
      paper, we identified a novel nuclear protein, Csi1, that localized to the site of
      centromere attachment and interacted with both the inner nuclear envelope SUN
      domain protein Sad1 and centromeres. Both Csi1 and Sad1 mutants exhibited
      centromere clustering defects in a high percentage of cells. Csi1 mutants also
      displayed a high rate of chromosome loss during mitosis, significant mitotic
      delays, and sensitivity to perturbations in microtubule-kinetochore interactions
      and chromosome numbers. These studies thus define a molecular link between the
      centromere and nuclear envelope that is responsible for centromere clustering.

PMID- 23166350
TI  - Mitotic chromosomes are compacted laterally by KIF4 and condensin and axially by
      topoisomerase IIalpha.
AB  - Mitotic chromosome formation involves a relatively minor condensation of the
      chromatin volume coupled with a dramatic reorganization into the characteristic
      "X" shape. Here we report results of a detailed morphological analysis, which
      revealed that chromokinesin KIF4 cooperated in a parallel pathway with condensin
      complexes to promote the lateral compaction of chromatid arms. In this analysis,
      KIF4 and condensin were mutually dependent for their dynamic localization on the
      chromatid axes. Depletion of either caused sister chromatids to expand and
      compromised the "intrinsic structure" of the chromosomes (defined in an in vitro
      assay), with loss of condensin showing stronger effects. Simultaneous depletion
      of KIF4 and condensin caused complete loss of chromosome morphology. In these
      experiments, topoisomerase IIalpha contributed to shaping mitotic chromosomes by
      promoting the shortening of the chromatid axes and apparently acting in
      opposition to the actions of KIF4 and condensins. These three proteins are major
      determinants in shaping the characteristic mitotic chromosome morphology.

PMID- 23166351
TI  - MARCH2 promotes endocytosis and lysosomal sorting of carvedilol-bound beta(2)
      adrenergic receptors.
AB  - Lysosomal degradation of ubiquitinated beta(2)-adrenergic receptors (beta(2)ARs)
      serves as a major mechanism of long-term desensitization in response to prolonged
      agonist stimulation. Surprisingly, the betaAR antagonist carvedilol also induced
      ubiquitination and lysosomal trafficking of both endogenously expressed
      beta(2)ARs in vascular smooth muscle cells (VSMCs) and overexpressed Flag
      beta(2)ARs in HEK-293 cells. Carvedilol prevented beta(2)AR recycling, blocked
      recruitment of Nedd4 E3 ligase, and promoted the dissociation of the
      deubiquitinases USP20 and USP33. Using proteomics approaches (liquid
      chromatography-tandem mass spectrometry), we identified that the E3 ligase MARCH2
      interacted with carvedilol-bound beta(2)AR. The association of MARCH2 with
      internalized beta(2)ARs was stabilized by carvedilol and did not involve beta
      arrestin. Small interfering RNA-mediated down-regulation of MARCH2 ablated
      carvedilol-induced ubiquitination, endocytosis, and degradation of endogenous
      beta(2)ARs in VSMCs. These findings strongly suggest that specific ligands
      recruit distinct E3 ligase machineries to activated cell surface receptors and
      direct their intracellular itinerary. In response to beta blocker therapy with
      carvedilol, MARCH2 E3 ligase activity regulates cell surface beta(2)AR expression
      and, consequently, its signaling.

PMID- 23166352
TI  - Charcot-Marie-Tooth disease-linked protein SIMPLE functions with the ESCRT
      machinery in endosomal trafficking.
AB  - Mutations in small integral membrane protein of lysosome/late endosome (SIMPLE)
      cause autosomal dominant, Charcot-Marie-Tooth disease (CMT) type 1C. The cellular
      function of SIMPLE is unknown and the pathogenic mechanism of SIMPLE mutations
      remains elusive. Here, we report that SIMPLE interacted and colocalized with
      endosomal sorting complex required for transport (ESCRT) components STAM1, Hrs,
      and TSG101 on early endosomes and functioned with the ESCRT machinery in the
      control of endosome-to-lysosome trafficking. Our analyses revealed that SIMPLE
      was required for efficient recruitment of ESCRT components to endosomal membranes
      and for regulating endosomal trafficking and signaling attenuation of ErbB
      receptors. We found that the ability of SIMPLE to regulate ErbB trafficking and
      signaling was impaired by CMT-linked SIMPLE mutations via a loss-of-function,
      dominant-negative mechanism, resulting in prolonged activation of ERK1/2
      signaling. Our findings indicate a function of SIMPLE as a regulator of endosomal
      trafficking and provide evidence linking dysregulated endosomal trafficking to
      CMT pathogenesis.

PMID- 23166353
TI  - Molecular characterization of the fatty alcohol oxidation pathway for wax-ester
      mobilization in germinated jojoba seeds.
AB  - Jojoba (Simmondsia chinensis) is the only plant species known to use liquid wax
      esters (WEs) as a primary seed storage reserve. Upon germination, WE hydrolysis
      releases very-long-chain fatty alcohols, which must be oxidized to fatty acids by
      the sequential action of a fatty alcohol oxidase (FAO) and a fatty aldehyde
      dehydrogenase (FADH) before they can be beta-oxidized. Here, we describe the
      cloning and characterization of genes for each of these two activities. Jojoba
      FAO and FADH are 52% and 68% identical to Arabidopsis (Arabidopsis thaliana) FAO3
      and ALDH3H1, respectively. The genes are expressed most strongly in the
      cotyledons of jojoba seedlings following germination, but transcripts can also be
      detected in vegetative tissues. Proteomic analysis indicated that the FAO and
      FADH proteins can be detected on wax bodies, but they localized to the
      endoplasmic reticulum when they were expressed as amino-terminal green
      fluorescent protein fusions in tobacco (Nicotiana tabacum) leaves. Recombinant
      jojoba FAO and FADH proteins are active on very-long-chain fatty alcohol and
      fatty aldehyde substrates, respectively, and have biochemical properties
      consistent with those previously reported in jojoba cotyledons. Coexpression of
      jojoba FAO and FADH in Arabidopsis enhanced the in vivo rate of fatty alcohol
      oxidation more than 4-fold. Taken together, our data suggest that jojoba FAO and
      FADH constitute the very-long-chain fatty alcohol oxidation pathway that is
      likely to be necessary for efficient WE mobilization following seed germination.

PMID- 23166354
TI  - Metabolic engineering of tomato fruit organic acid content guided by biochemical
      analysis of an introgression line.
AB  - Organic acid content is regarded as one of the most important quality traits of
      fresh tomato (Solanum lycopersicum). However, the complexity of carboxylic acid
      metabolism and storage means that it is difficult to predict the best way to
      engineer altered carboxylic acid levels. Here, we used a biochemical analysis of
      a tomato introgression line with increased levels of fruit citrate and malate at
      breaker stage to identify a metabolic engineering target that was subsequently
      tested in transgenic plants. Increased carboxylic acid levels in introgression
      line 2-5 were not accompanied by changes in the pattern of carbohydrate oxidation
      by pericarp discs or the catalytic capacity of tricarboxylic acid cycle enzymes
      measured in isolated mitochondria. However, there was a significant decrease in
      the maximum catalytic activity of aconitase in total tissue extracts, suggesting
      that a cytosolic isoform of aconitase was affected. To test the role of cytosolic
      aconitase in controlling fruit citrate levels, we analyzed fruit of transgenic
      lines expressing an antisense construct against SlAco3b, one of the two tomato
      genes encoding aconitase. A green fluorescent protein fusion of SlAco3b was dual
      targeted to cytosol and mitochondria, while the other aconitase, SlAco3a, was
      exclusively mitochondrial when transiently expressed in tobacco (Nicotiana
      tabacum) leaves. Both aconitase transcripts were decreased in fruit from
      transgenic lines, and aconitase activity was reduced by about 30% in the
      transgenic lines. Other measured enzymes of carboxylic acid metabolism were not
      significantly altered. Both citrate and malate levels were increased in ripe
      fruit of the transgenic plants, and as a consequence, total carboxylic acid
      content was increased by 50% at maturity.

PMID- 23166355
TI  - Identification of two novel endoplasmic reticulum body-specific integral membrane
      proteins.
AB  - The endoplasmic reticulum (ER) body, a large compartment specific to the
      Brassicales, accumulates beta-glucosidase and possibly plays a role in the
      defense against pathogens and herbivores. Although the ER body is a subdomain of
      the ER, it is unclear whether any ER body-specific membrane protein exists. In
      this study, we identified two integral membrane proteins of the ER body in
      Arabidopsis (Arabidopsis thaliana) and termed them MEMBRANE PROTEIN OF
      ENDOPLASMIC RETICULUM BODY1 (MEB1) and MEB2. In Arabidopsis, a basic helix-loop
      helix transcription factor, NAI1, and an ER body component, NAI2, regulate ER
      body formation. The expression profiles of MEB1 and MEB2 are similar to those of
      NAI1, NAI2, and ER body beta-glucosidase PYK10 in Arabidopsis. The expression of
      MEB1 and MEB2 was reduced in the nai1 mutant, indicating that NAI1 regulates the
      expression of MEB1 and MEB2 genes. MEB1 and MEB2 proteins localize to the ER body
      membrane but not to the ER network, suggesting that these proteins are
      specifically recruited to the ER body membrane. MEB1 and MEB2 physically
      interacted with ER body component NAI2, and they were diffused throughout the ER
      network in the nai2 mutant, which has no ER body. Heterologous expression of MEB1
      and MEB2 in yeast (Saccharomyces cerevisiae) suppresses iron and manganese
      toxicity, suggesting that MEB1 and MEB2 are metal transporters. These results
      indicate that the membrane of ER bodies has specific membrane proteins and
      suggest that the ER body is involved in defense against metal stress as well as
      pathogens and herbivores.

PMID- 23166356
TI  - BCL6 positively regulates AID and germinal center gene expression via repression
      of miR-155.
AB  - The BCL6 proto-oncogene encodes a transcriptional repressor that is required for
      germinal center (GC) formation and whose de-regulation is involved in
      lymphomagenesis. Although substantial evidence indicates that BCL6 exerts its
      function by repressing the transcription of hundreds of protein-coding genes, its
      potential role in regulating gene expression via microRNAs (miRNAs) is not known.
      We have identified a core of 15 miRNAs that show binding of BCL6 in their genomic
      loci and are down-regulated in GC B cells. Among BCL6 validated targets, miR-155
      and miR-361 directly modulate AID expression, indicating that via repression of
      these miRNAs, BCL6 up-regulates AID. Similarly, the expression of additional
      genes relevant for the GC phenotype, including SPI1, IRF8, and MYB, appears to be
      sustained via BCL6-mediated repression of miR-155. These findings identify a
      novel mechanism by which BCL6, in addition to repressing protein coding genes,
      promotes the expression of important GC functions by repressing specific miRNAs.

PMID- 23166357
TI  - RAE-1 ligands for the NKG2D receptor are regulated by E2F transcription factors,
      which control cell cycle entry.
AB  - The NKG2D stimulatory receptor expressed by natural killer cells and T cell
      subsets recognizes cell surface ligands that are induced on transformed and
      infected cells and facilitate immune rejection of tumor cells. We demonstrate
      that expression of retinoic acid early inducible gene 1 (RAE-1) family NKG2D
      ligands in cancer cell lines and proliferating normal cells is coupled directly
      to cell cycle regulation. Raet1 genes are directly transcriptionally activated by
      E2F family transcription factors, which play a central role in regulating cell
      cycle entry. Induction of RAE-1 occurred in primary cell cultures, embryonic
      brain cells in vivo, and cells in healing skin wounds and, accordingly, wound
      healing was delayed in mice lacking NKG2D. Transcriptional activation by E2Fs is
      likely coordinated with posttranscriptional regulation by other stress responses.
      These findings suggest that cellular proliferation, as occurs in cancer cells but
      also other pathological conditions, is a key signal tied to immune reactions
      mediated by NKG2D-bearing lymphocytes.

PMID- 23166359
TI  - Thermographic and clinical correlation of myofascial trigger points in the
      masticatory muscles.
AB  - OBJECTIVES: The aim of the study was to identify and correlate myofascial trigger
      points (MTPs) in the masticatory muscles, using thermography and algometry.
      METHODS: 26 female volunteers were recruited. The surface facial area over the
      masseter and anterior temporalis muscles was divided into 15 subareas on each
      side (n=780). This investigation consisted of three steps. The first step
      involved thermographic facial examination, using lateral views. The second step
      involved the pressure pain threshold (PPT), marking the MTP pattern areas for
      referred pain (n=131) and local pain (n=282) with a coloured pencil, and a
      photograph of the lateral face with the head in the same position as the infrared
      imaging. The last step was the fusion of these two images, using dedicated
      software (Reporter(r) 8.5-SP3 Professional Edition and QuickReport(r) 1.2, FLIR
      Systems, Wilsonville, OR); and the calculation of the temperature of each point.
      RESULTS: PPT levels measured at the points of referred pain in MTPs (1.28+/-0.45
      kgf) were significantly lower than the points of local pain in MTPs (1.73+/-0.59
      kgf; p<0.05). Infrared imaging indicated differences between referred and local
      pain in MTPs of 0.5  degrees C (p<0.05). Analysis of the correlation between the
      PPT and infrared imaging was done using the Spearman non-parametric method, in
      which the correlations were positive and moderate (0.4<=r<0.7). The sensitivity
      and specificity in MTPs were 62.5% and 71.3%, respectively, for referred pain,
      and 43.6% and 60.6%, respectively, for local pain. CONCLUSION: Infrared imaging
      measurements can provide a useful, non-invasive and non-ionizing examination for
      diagnosis of MTPs in masticatory muscles.

PMID- 23166358
TI  - Local changes in lipid environment of TCR microclusters regulate membrane binding
      by the CD3epsilon cytoplasmic domain.
AB  - The CD3epsilon and zeta cytoplasmic domains of the T cell receptor bind to the
      inner leaflet of the plasma membrane (PM), and a previous nuclear magnetic
      resonance structure showed that both tyrosines of the CD3epsilon immunoreceptor
      tyrosine-based activation motif partition into the bilayer. Electrostatic
      interactions between acidic phospholipids and clusters of basic CD3epsilon
      residues were previously shown to be essential for CD3epsilon and zeta membrane
      binding. Phosphatidylserine (PS) is the most abundant negatively charged lipid on
      the inner leaflet of the PM and makes a major contribution to membrane binding by
      the CD3epsilon cytoplasmic domain. Here, we show that TCR triggering by peptide-
      MHC complexes induces dissociation of the CD3epsilon cytoplasmic domain from the
      plasma membrane. Release of the CD3epsilon cytoplasmic domain from the membrane
      is accompanied by a substantial focal reduction in negative charge and available
      PS in TCR microclusters. These changes in the lipid composition of TCR
      microclusters even occur when TCR signaling is blocked with a Src kinase
      inhibitor. Local changes in the lipid composition of TCR microclusters thus
      render the CD3epsilon cytoplasmic domain accessible during early stages of T cell
      activation.

PMID- 23166360
TI  - Quantitative MRI analysis of salivary glands in sickle cell disease.
AB  - OBJECTIVES: The purpose of this prospective study was to characterize the MR
      relaxometric features of the major salivary glands in patients with sickle cell
      disease (SCD). METHODS: 15 patients with SCD (aged 19.8-43.6 years) and 12
      controls were imaged with the mixed turbo-spin echo pulse sequence. The major
      salivary glands were manually segmented and T1, T2 and secular T2 relaxometry
      histograms were modelled with Gaussian functions. RESULTS: Shortened T1
      relaxation times were seen solely in the submandibular glands of patients with
      SCD (747.5+/-54.8 ms vs 807.1+/-38.3 ms, p<0.001). Slight T2 and secular T2
      shortening were seen in the parotid gland; however, this difference was not
      significant (p=0.07). The sublingual gland showed no changes under MR
      relaxometry. There was no difference in glandular volumes, and no correlation was
      demonstrated between history of blood transfusion and salivary gland relaxometry.
      CONCLUSIONS: Patients with SCD exhibited changes in quantitative MRI T1
      relaxometry histograms of the submandibular glands.

PMID- 23166361
TI  - Influence of scan setting selections on root canal visibility with cone beam CT.
AB  - OBJECTIVES: The aim of this study was to assess the influence of scan setting
      selection, including field of view (FOV) ranging from small to large, number of
      projections and scan modes on the visibility of the root canal with cone beam CT
      (CBCT). METHODS: One human mandible cadaver was scanned with CBCT (Accuitomo 170;
      J Morita MPG Corp., Kyoto, Japan) using six different FOVs (4*4 cm, 6*6 cm, 8*8
      cm, 10*10 cm, 14*10 cm and 17*12 cm) with either 360 or 180 projections in
      standard and high resolution. The right canine was selected for evaluation. Ten
      observers independently assessed the visibility of the canal space and overall
      image quality on a five-point scale. RESULTS: The results indicate that both
      selections of FOV and number of projections have significant influence on root
      canal visibility (p=0.0001), whereas scan mode, whether standard or high
      resolution, was less relevant (p=0.34). CONCLUSIONS: The smallest FOV available
      should always be used for endodontic applications, and it is not recommended to
      reduce the number of projections to 180. Using the standard scan mode instead of
      high resolution does not negatively influence the visibility of the root canal
      space and is therefore recommended.

PMID- 23166362
TI  - Effect of voxel size on the accuracy of 3D reconstructions with cone beam CT.
AB  - OBJECTIVES: The various types of cone beam CT (CBCT) differ in several technical
      characteristics, notably their spatial resolution, which is defined by the
      acquisition voxel size. However, data are still lacking on the effects of voxel
      size on the metric accuracy of three-dimensional (3D) reconstructions. This study
      was designed to assess the effect of isotropic voxel size on the 3D
      reconstruction accuracy and reproducibility of CBCT data. METHODS: The study
      sample comprised 70 teeth (from the Institut d'Anatomie Normale, Strasbourg,
      France). The teeth were scanned with a KODAK 9500 3D(r) CBCT (Carestream Health,
      Inc., Marne-la-Vallee, France), which has two voxel sizes: 200 um (CBCT 200 um
      group) and 300 um (CBCT 300 um group). These teeth had also been scanned with the
      KODAK 9000 3D(r) CBCT (Carestream Health, Inc.) (CBCT 76 um group) and the SCANCO
      Medical micro-CT XtremeCT (SCANCO Medical, Bruttisellen, Switzerland) (micro-CT
      41 um group) considered as references. After semi-automatic segmentation with
      AMIRA(r) software (Visualization Sciences Group, Burlington, MA), tooth
      volumetric measurements were obtained. RESULTS: The Bland-Altman method showed no
      difference in tooth volumes despite a slight underestimation for the CBCT 200 um
      and 300 um groups compared with the two reference groups. The underestimation was
      statistically significant for the volumetric measurements of the CBCT 300 um
      group relative to the two reference groups (Passing-Bablok method). CONCLUSIONS:
      CBCT is not only a tool that helps in diagnosis and detection but it has the
      complementary advantage of being a measuring instrument, the accuracy of which
      appears connected to the size of the voxels. Future applications of such
      measurements with CBCT are discussed.

PMID- 23166363
TI  - Synovial chondromatosis of the temporomandibular joint with calcium pyrophosphate
      dihydrate crystal deposition disease (pseudogout).
AB  - This report describes a very rare case of synovial chondromatosis with deposition
      of calcium pyrophosphate dihydrate (CPPD) crystals (pseudogout) in the
      temporomandibular joint (TMJ) of a 46-year-old male patient. Synovial
      chondromatosis is a non-neoplastic disease characterized by metaplasia of the
      connective tissue leading to chondrogenesis in the synovial membrane. Pseudogout
      is an inflammatory disease of the joints caused by the deposition of CPPD,
      producing similar symptoms to those observed in gout but not hyperuricaemia. Both
      diseases commonly affect the knee, hip and elbow joints, but rarely affect the
      TMJ.

PMID- 23166364
TI  - Effectiveness of bone scans in the diagnosis of osteoarthritis of the
      temporomandibular joint.

PMID- 23166367
TI  - The roles of glial cell line-derived neurotrophic factor, brain-derived
      neurotrophic factor and nerve growth factor during the final stage of
      folliculogenesis: a focus on oocyte maturation.
AB  - Neurotrophic factors were first identified to promote the growth, survival or
      differentiation of neurons and have also been associated with the early stages of
      ovarian folliculogenesis. More recently, their effects on the final stage of
      follicular development, including oocyte maturation and early embryonic
      development, have been reported. Glial cell line-derived neurotrophic factor
      (GDNF), brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF),
      which are expressed in numerous peripheral tissues outside of the CNS, most
      notably the ovary, are now known to stimulate oocyte maturation in various
      species, also enhancing developmental competence. The mechanisms that underlie
      their actions in antral follicles, as well as the targets ultimately controlled
      by these factors, are beginning to emerge. GDNF, BDNF and NGF, alone or in
      combination, could be added to the media currently utilized for in vitro oocyte
      maturation, thereby potentially increasing the production and/or quality of early
      embryos.

PMID- 23166368
TI  - The function of chaperone proteins in the assemblage of protein complexes
      involved in gamete adhesion and fusion processes.
AB  - The remarkable complexity of the molecular events governing adhesion and fusion
      of the male and female gametes is becoming apparent. Novel research suggests that
      these highly specific cellular interactions are facilitated by multiprotein
      complexes that are delivered to and/or assembled on the surface of the gametes by
      molecular chaperones in preparation for sperm-egg interaction. While the
      activation of these molecular chaperones and the mechanisms by which they shuttle
      proteins to the surface of the cell remain the subject of ongoing investigation,
      a compelling suggestion is that these processes are augmented by dynamic membrane
      microdomains or lipid rafts that migrate to the apical region of the sperm head
      after capacitation. Preliminary studies of the oocyte plasma membrane have also
      revealed the presence of lipid rafts comprising several molecular chaperones,
      raising the possibility that similar mechanisms may be involved in the activation
      of maternal fusion machinery and the regulation of oocyte plasma membrane
      integrity. Despite these findings, the analysis of oocyte surface multiprotein
      complexes is currently lacking. Further analyses of the intermediary proteins
      that facilitate the expression of key players in sperm-egg fusion are likely to
      deliver important insights into this unique event, which culminates in the
      cytoplasmic continuity of the male and female gametes.

PMID- 23166366
TI  - The Notch pathway controls fibrotic and regenerative repair in the adult heart.
AB  - AIMS: In the adult heart, Notch signalling regulates the response to injury.
      Notch inhibition leads to increased cardiomyocyte apoptosis, and exacerbates the
      development of cardiac hypertrophy and fibrosis. The role of Notch in the
      mesenchymal stromal cell fraction, which contains cardiac fibroblasts and cardiac
      precursor cells, is, however, largely unknown. In the present study, we evaluate,
      therefore, whether forced activation of the Notch pathway in mesenchymal stromal
      cells regulates pathological cardiac remodelling. METHODS AND RESULTS: We
      generated transgenic mice overexpressing the Notch ligand Jagged1 on the surface
      of cardiomyocytes to activate Notch signalling in adjacent myocyte and non
      myocyte cells. In neonatal transgenic mice, activated Notch sustained cardiac
      precursor and myocyte proliferation after birth, and led to increased numbers of
      cardiac myocytes in adult mice. In the adult heart under pressure overload, Notch
      inhibited the development of cardiomyocyte hypertrophy and transforming growth
      factor-beta/connective tissue growth factor-mediated cardiac fibrosis. Most
      importantly, Notch activation in the stressed adult heart reduced the
      proliferation of myofibroblasts and stimulated the expansion of stem cell antigen
      1-positive cells, and in particular of Nkx2.5-positive cardiac precursor cells.
      CONCLUSIONS: We conclude that Notch is pivotal in the healing process of the
      injured heart. Specifically, Notch regulates key cellular mechanisms in the
      mesenchymal stromal cell population, and thereby controls the balance between
      fibrotic and regenerative repair in the adult heart. Altogether, these findings
      indicate that Notch represents a unique therapeutic target for inducing
      regeneration in the adult heart via mobilization of cardiac precursor cells.

PMID- 23166369
TI  - Effect of sialylation and complexity of FSH oligosaccharides on inhibin
      production by granulosa cells.
AB  - Granulosa cell (GC) inhibin A and B production is regulated by FSH and gonadal
      factors. This gonadotrophin is released as a mixture of glycoforms, which induce
      different biological responses in vivo and in vitro. Our aim was to determine the
      effect of recombinant human FSH (rhFSH) glycosylation variants on inhibin A and B
      production by rat GCs. Preparative isoelectro focusing was used to isolate more
      acidic/sialylated (pH <4.00) and less acidic/sialylated (pH >5.00) rhFSH charge
      analogues. Concanavalin A was used to isolate unbound and firmly bound rhFSH
      glycoforms on the basis of their oligosaccharide complexity. GCs, obtained from
      oestrogen-primed immature rats, were cultured with either native rhFSH or its
      glycosylation variants. Inhibin A and B were determined using specific ELISAs.
      Results were expressed as mean+/-s.e.m. Under basal conditions, inhibin A was the
      predominant dimer produced (inhibin A: 673+/-55; inhibin B: 80+/-4  pg/ml). More
      acidic/sialylated charge analogues stimulated inhibin B production when compared
      to inhibin A at all doses studied; by contrast, less acidic/sialylated charge
      analogues stimulated inhibin A production and elicited no effect on inhibin B.
      Glycoforms bearing complex oligosaccharides showed a potent stimulatory effect on
      inhibin B when compared to inhibin A production (i.e. dose 1  ng/ml: 4.9+/-0.5 vs
      0.9+/-0.1-fold stimulation, P<0.001). Glycoforms bearing hybrid-type
      oligosaccharides favoured inhibin A production (i.e. dose 4  ng/ml 2.9+/-0.1 vs
      1.6+/-0.1-fold stimulation, P<0.05). These results show that the sialylation
      degree as well as the complexity of oligosaccharides present in the rhFSH
      molecule may be considered additional factors that differentially regulate
      dimeric inhibin production by rat GCs.

PMID- 23166370
TI  - S1P and the birth of platelets.
AB  - Recent work has highlighted the multitude of biological functions of sphingosine
      1-phosphate (S1P), which include roles in hematopoietic cell trafficking,
      organization of immune organs, vascular development, and neuroinflammation.
      Indeed, a functional antagonist of S1P(1) receptor, FTY720/Gilenya, has entered
      the clinic as a novel therapeutic for multiple sclerosis. In this issue of the
      JEM, Zhang et al. highlight yet another function of this lipid mediator:
      thrombopoiesis. The S1P(1) receptor is required for the growth of proplatelet
      strings in the bloodstream and the shedding of platelets into the circulation.
      Notably, the sharp gradient of S1P between blood and the interstitial fluids
      seems to be essential to ensure the production of platelets, and S1P appears to
      cooperate with the CXCL12-CXCR4 axis. Pharmacologic modulation of the S1P(1)
      receptor altered circulating platelet numbers acutely, suggesting a potential
      therapeutic strategy for controlling thrombocytopenic states. However, the S1P(4)
      receptor may also regulate thrombopoiesis during stress-induced accelerated
      platelet production. This work reveals a novel physiological action of the
      S1P/S1P(1) duet that could potentially be harnessed for clinical translation.

PMID- 23166372
TI  - Phenological response of grassland species to manipulative snowmelt and drought
      along an altitudinal gradient.
AB  - Plant communities in the European Alps are assumed to be highly affected by
      climate change, as the temperature rise in this region is above the global
      average. It is predicted that higher temperatures will lead to advanced snowmelt
      dates and that the number of extreme weather events will increase. The aims of
      this study were to determine the impacts of extreme climatic events on flower
      phenology and to assess whether those impacts differed between lower and higher
      altitudes. In 2010, an experiment simulating advanced and delayed snowmelt as
      well as a drought event was conducted along an altitudinal transect approximately
      every 250 m (600-2000 m above sea level) in the Berchtesgaden National Park,
      Germany. The study showed that flower phenology was strongly affected by
      altitude; however, there were few effects of the manipulative treatments on
      flowering. The effects of advanced snowmelt were significantly greater at higher
      than at lower sites, but no significant difference was found between both
      altitudinal bands for the other treatments. The response of flower phenology to
      temperature declined through the season and the length of flowering duration was
      not significantly influenced by treatments. The stronger effect of advanced
      snowmelt at higher altitudes may be a response to differences in treatment
      intensity across the gradient. Consequently, shifts in the date of snowmelt due
      to global warming may affect species more at higher than at lower altitudes, as
      changes may be more pronounced at higher altitudes. These data indicate a rather
      low risk of drought events on flowering phenology in the Bavarian Alps.

PMID- 23166371
TI  - Developmental onset of reproductive barriers and associated proteome changes in
      stigma/styles of Solanum pennellii.
AB  - Although self-incompatibility (SI) in plants has been studied extensively, far
      less is known about interspecific reproductive barriers. One interspecific
      barrier, known as unilateral incongruity or incompatibility (UI), occurs when
      species display unidirectional compatibility in interspecific crosses. In the
      wild tomato species Solanum pennellii, both SI and self-compatible (SC)
      populations express UI when crossed with domesticated tomato, offering a useful
      model system to dissect the molecular mechanisms involved in reproductive
      barriers. In this study, the timing of reproductive barrier establishment during
      pistil development was determined in SI and SC accessions of S. pennellii using a
      semi-in vivo system to track pollen-tube growth in developing styles. Both SI and
      UI barriers were absent in styles 5 days prior to flower opening, but were
      established by 2 days before flower opening, with partial barriers detected
      during a transition period 3-4 days before flower opening. The developmental
      expression dynamics of known SI factors, S-RNases and HT proteins, was also
      examined. The accumulation of HT-A protein coincided temporally and spatially
      with UI barriers in developing pistils. Proteomic analysis of stigma/styles from
      key developmental stages showed a switch in protein profiles from cell-division
      associated proteins in immature stigma/styles to a set of proteins in mature
      stigma/styles that included S-RNases, HT-A protein and proteins associated with
      cell-wall loosening and defense responses, which could be involved in pollen
      pistil interactions. Other prominent proteins in mature stigma/styles were those
      involved in lipid metabolism, consistent with the accumulation of lipid-rich
      material during pistil maturation.

PMID- 23166373
TI  - Six degrees of separation: use of social network analysis to better understand
      outbreaks of nosocomial transmission of extensively drug-resistant tuberculosis.

PMID- 23166375
TI  - Emergent magnetic monopoles in frustrated magnetic systems.

PMID- 23166376
TI  - Magnetic monopoles in field theory and cosmology.
AB  - The existence of magnetic monopoles is predicted by many theories of particle
      physics beyond the standard model. However, in spite of extensive searches, there
      is no experimental or observational sign of them. I review the role of magnetic
      monopoles in quantum field theory and discuss their implications for particle
      physics and cosmology. I also highlight their differences and similarities with
      monopoles found in frustrated magnetic systems.

PMID- 23166377
TI  - Magnetic charge and ordering in kagome spin ice.
AB  - We present a numerical study of magnetic ordering in spin ice on kagome, a two
      dimensional lattice of corner-sharing triangles. The magnet has six ground states
      and the ordering occurs in two stages, as one might expect for a six-state clock
      model. In spin ice with short-range interactions up to second neighbours, there
      is an intermediate critical phase separated from the paramagnetic and ordered
      phases by Kosterlitz-Thouless (KT) transitions. In dipolar spin ice, the
      intermediate phase has long-range order of staggered magnetic charges. The high-
      and low-temperature phase transitions are of the Ising and 3-state Potts
      universality classes, respectively. Freeze-out of defects in the charge order
      produce a very large spin correlation length in the intermediate phase. As a
      result of that, the lower-temperature transition appears to be of the KT type.

PMID- 23166374
TI  - Nosocomial transmission of extensively drug-resistant tuberculosis in a rural
      hospital in South Africa.
AB  - BACKGROUND: Extensively drug-resistant tuberculosis (XDR-tuberculosis) is a
      global public health threat, but few data exist elucidating factors driving this
      epidemic. The initial XDR-tuberculosis report from South Africa suggested
      transmission is an important factor, but detailed epidemiologic and molecular
      analyses were not available for further characterization. METHODS: We performed a
      retrospective, observational study among XDR-tuberculosis patients to identify
      hospital-associated epidemiologic links. We used spoligotyping, IS6110-based
      restriction fragment-length polymorphism analysis, and sequencing of resistance
      determining regions to identify clusters. Social network analysis was used to
      construct transmission networks among genotypically clustered patients. RESULTS:
      Among 148 XDR-tuberculosis patients, 98% were infected with human
      immunodeficiency virus (HIV), and 59% had smear-positive tuberculosis. Nearly all
      (93%) were hospitalized while infectious with XDR-tuberculosis (median duration,
      15 days; interquartile range: 10-25 days). Genotyping identified a predominant
      cluster comprising 96% of isolates. Epidemiologic links were identified for 82%
      of patients; social network analysis demonstrated multiple generations of
      transmission across a highly interconnected network. CONCLUSIONS: The XDR
      tuberculosis epidemic in Tugela Ferry, South Africa, has been highly clonal.
      However, the epidemic is not the result of a point-source outbreak; rather, a
      high degree of interconnectedness allowed multiple generations of nosocomial
      transmission. Similar to the outbreaks of multidrug-resistant tuberculosis in the
      1990s, poor infection control, delayed diagnosis, and a high HIV prevalence
      facilitated transmission. Important lessons from those outbreaks must be applied
      to stem further expansion of this epidemic.

PMID- 23166378
TI  - Generalized longitudinal susceptibility for magnetic monopoles in spin ice.
AB  - The generalized longitudinal susceptibility chi(q,omega) affords a sensitive
      measure of the spatial and temporal correlations of magnetic monopoles in spin
      ice. Starting with the monopole model, a mean field expression for chi(q,omega)
      is derived as well as expressions for the mean square longitudinal field and
      induction at a point. Monopole motion is shown to be strongly correlated, and
      both spatial and temporal correlations are controlled by the dimensionless
      monopole density x which defines the ratio of the magnetization relaxation rate
      and the monopole hop rate. Thermal effects and spin-lattice relaxation are also
      considered. The derived equations are applicable in the temperature range where
      the Wien effect for magnetic monopoles is negligible. They are discussed in the
      context of existing theories of spin ice and the following experimental
      techniques: DC and AC magnetization, neutron scattering, neutron spin echo and
      longitudinal and transverse field MUSR. The monopole theory is found to unify
      diverse experimental results, but several discrepancies between theory and
      experiment are identified. One of these, concerning the neutron scattering line
      shape, is explained by means of a phenomenological modification to the theory.

PMID- 23166379
TI  - Artificial kagome spin ice: dimensional reduction, avalanche control and emergent
      magnetic monopoles.
AB  - Artificial spin-ice systems consisting of nanolithographic arrays of isolated
      nanomagnets are model systems for the study of frustration-induced phenomena. We
      have recently demonstrated that monopoles and Dirac strings can be directly
      observed via synchrotron-based photoemission electron microscopy, where the
      magnetic state of individual nanoislands can be imaged in real space. These
      experimental results of Dirac string formation are in excellent agreement with
      Monte Carlo simulations of the hysteresis of an array of dipoles situated on a
      kagome lattice with randomized switching fields. This formation of one
      dimensional avalanches in a two-dimensional system is in sharp contrast to
      disordered thin films, where avalanches associated with magnetization reversal
      are two-dimensional. The self-organized restriction of avalanches to one
      dimension provides an example of dimensional reduction due to frustration. We
      give simple explanations for the origin of this dimensional reduction and discuss
      the disorder dependence of these avalanches. We conclude with the explicit
      demonstration of how these avalanches can be controlled via locally modified
      anisotropies. Such a controlled start and stop of avalanches will have potential
      applications in data storage and information processing.

PMID- 23166380
TI  - Magnetic dipole configurations on honeycomb lattices: effect of finite size and
      boundaries.
AB  - Artificial dipolar spin-ice patterns have attracted much attention recently
      because of their rich configurations and excitations in the form of Dirac strings
      connecting magnetic monopoles. We have analysed the distribution of excitations
      in the form of strings and vertices carrying magnetic charges Q=+/-3q in
      honeycomb artificial spin-ice patterns. Two types of patterns are compared, those
      that terminate with open hexagons and those with closed hexagons. The dipole
      configurations and the frequency of spin-ice rule-violating Q=+/-3q vertices
      depend slightly on the boundary conditions of the pattern. Upon rotation of the
      patterns by 2pi in a coercive magnetic field of 500 Oe, complete reversibility of
      the charge and string configuration is observed.

PMID- 23166381
TI  - Domain wall interactions at a cross-shaped vertex.
AB  - The interaction of two domain walls (DWs) at a cross-shaped vertex fabricated
      from two ferromagnetic nanowires has been experimentally investigated. Both
      magnetostatically repulsive and attractive interactions have been probed. It is
      found that in the repulsive case, a passing DW may directly induce the depinning
      of another that is already pinned at a vertex. This effect can be qualitatively
      described by considering only simple, magnetostatic-charge-based arguments. In
      the attractive case, however, asymmetric pinning is found, with complete
      suppression of depinning possible. This observed effect is contrary to simple
      charge-based arguments and highlights the need for full micromagnetic
      characterization of the DW interactions in more complex systems.

PMID- 23166382
TI  - Gauge fields in real and momentum spaces in magnets: monopoles and skyrmions.
AB  - Electronic states in magnets are characterized by the quantum mechanical Berry
      phase defined in both the real and momentum spaces. This Berry phase constitutes
      the gauge fields, i.e. the emergent electromagnetic fields in solids, and affects
      the motion of the electrons. In momentum space, the band crossings act as the
      magnetic monopoles, i.e. the sources or sinks of the gauge flux. In real space,
      the spin textures with non-coplanar spin configurations produce the gauge field
      by the solid angle leading to the spin chirality. Skyrmion is the representative
      structure supporting this gauge field. A typical phenomenon reflecting this gauge
      field is the anomalous Hall effect, i.e. the Hall effect produced by the
      spontaneous magnetization combined with the relativistic spin-orbit interaction.
      We discuss a few examples recently studied related to these issues with some new
      results on skyrmion formation.

PMID- 23166383
TI  - Evaluation of newspaper articles for coverage of public reporting data: a case
      study of unadjusted cancer survival data.
AB  - The Japanese Association of Clinical Cancer Centers recently published the
      unadjusted 5-year survival rates of patients receiving care at each facility. A
      primary concern is that the media may cover this topic differently than
      originally intended. We examined all 13 newspaper articles that addressed the
      topic to assess their coverage of the public reporting program's key points,
      which were identified through interviews with the leader of the program. On
      average, 4.5 of the 10 key points identified were at least superficially covered.
      Although most articles mentioned the incomparability of the unadjusted data,
      eight created comparative tables that listed the survival data across facilities
      and seven sorted the facilities in descending order of survival. Four articles
      provided potentially misleading descriptions about the use of the relative
      survival. We concluded that caution is required because newspaper reports may
      convey potentially contradicting messages and technical details may be described
      inaccurately.

PMID- 23166384
TI  - A phase II clinical trial of endoscopic submucosal dissection for early gastric
      cancer of undifferentiated type: Japan Clinical Oncology Group study
      JCOG1009/1010.
AB  - A Phase II clinical trial has been initiated to evaluate the efficacy and safety
      of endoscopic submucosal dissection for intramucosal (cT1a) gastric cancer of
      undifferentiated type. Patients with cT1a gastric cancer with undifferentiated
      type adenocarcinoma are eligible for the study. The tumor size should be 2 cm or
      less without ulceration. The study will enroll a total of 325 patients from 51
      institutions over a 4-year period. The primary endpoint is proportion of 5-year
      overall survival (% 5-year overall survival) in patients with undifferentiated
      dominant type. The secondary endpoints are overall survival, relapse-free
      survival, distant metastasis-free survival, % 5-year overall survival without
      either recurrence or gastrectomy, % en-bloc resection with endoscopic submucosal
      dissection, % pathological curative resection with endoscopic submucosal
      dissection, % 5-year overall survival in patients with differentiated dominant
      type, % 5-year overall survival in patients with pathologically curative
      resection with endoscopic submucosal dissection and adverse events.

PMID- 23166385
TI  - Prognostic value of C-reactive protein, lactase dehydrogenase and anemia in
      recurrent or refractory aggressive lymphoma.
AB  - OBJECTIVE: Prognostic predictors for newly diagnosed malignant lymphoma are well
      known. However, they have not been compared for patients with recurrent or
      refractory malignant lymphoma. METHODS: We retrospectively analyzed biological
      prognostic predictors for patients with recurrent or refractory aggressive
      lymphoma, such as serum levels of C-reactive protein, lactate dehydrogenase,
      hemoglobin, beta2-microglobulin and soluble interleukin-2 receptor before salvage
      therapy. The primary endpoint was overall survival after salvage treatment.
      First, univariate and multivariate analyses were performed for each of the
      parameters, using the log-rank test and Cox regression analysis, respectively.
      Secondly, we classified the patients into three risk groups on the basis of
      significant poor predictors. RESULTS: Sixty-three patients, including 41 patients
      with diffuse large B-cell lymphoma, were included in this study. Overall survival
      was significantly worse in patients with elevated C-reactive protein level
      (hazard ratio 3.757; P = 0.017), elevated lactate dehydrogenase level (hazard
      ratio 3.948; P = 0.010) and anemia (hazard ratio 3.925; P = 0.016) by
      multivariate analysis. We classified patients into two groups based on these
      three biological parameters. The median overall survival of the high- and low
      risk patients was 5.8 and 60.1 months, respectively (log-rank test; P < 0.001).
      The overall response rate was significantly higher among the low-risk patients
      than among the high-risk patients (71.4 versus 28.6%, P = 0.005). Those results
      were similar among all aggressive lymphoma and diffuse large B-cell lymphoma.
      CONCLUSIONS: Elevated C-reactive protein level, elevated lactate dehydrogenase
      level and anemia before salvage treatment predicted poorer outcomes among
      patients with recurrent or refractory aggressive lymphoma.

PMID- 23166386
TI  - The association between perceived social support and continued smoking in cancer
      survivors.
AB  - OBJECTIVE: With the increased survival rate of cancer patients, positive changes
      in health behaviors, including smoking cessation, are becoming progressively more
      important. While studies in the general population have demonstrated the
      beneficial effects of high perceived support of smoking cessation and continuing
      abstinence, few studies have addressed such issues in cancer survivors. We
      examined the factors related to continued smoking among cancer survivors with
      specific attention given to the role of perceived social support. METHODS: A
      nationwide, multicenter survey was conducted with 1956 cancer patients. Smoking
      status at the time of diagnosis and at the time of survey, and perceived social
      support, as measured by the Duke-UNC Functional Social Support Questionnaire,
      were collected by self-reported questionnaire. RESULTS: Among 493 participants
      who were smoking at the time of cancer diagnosis, 131 (26.6%) were continued
      smokers at the time of survey. In a multivariate logistic regression analysis,
      current alcohol consumption (odds ratio, 3.29; 95% confidence interval, 1.91
      5.65), early cancer stage (P(for trend)< 0.01), lung cancer diagnosis (odds
      ratio, 0.41; 95% confidence interval, 0.19-0.88), and high perceived social
      support (odds ratio, 0.59; 95% confidence interval, 0.37-0.96) showed significant
      associations with continued smoking. CONCLUSIONS: Cancer survivors with low
      perceived social support were more likely to continue smoking. Our study suggests
      that perceived social support may be an important factor for smoking cessation
      and maintenance of smoking cessation in this population.

PMID- 23166387
TI  - Past, present, and future of palliative care in Japan.
AB  - Palliative care in Japan has developed through a number of transition stages. The
      first of these was the recognition of costs for care received at a palliative
      care unit as eligible for reimbursement under the medical insurance system. The
      second stage was the recognition of costs for care received from a hospital-based
      palliative care team as eligible for reimbursement under the medical insurance
      system. The third stage was government policy relating to palliative care,
      including establishment of the Cancer Control Act formulation of the Basic Plan
      to Promote Cancer Control Programs and implementation of the Promotion Plan for
      the Platform of Human Resource Development for Cancer. A total of 350 000 cancer
      patients died during fiscal 2011, of which 9% made use of a palliative care unit.
      The use of palliative care is steadily growing with a trend away from palliative
      care units toward palliative care teams and care in the home. Whereas it was once
      seen as the limited treatment of terminal care, palliative care is increasingly
      becoming integrated into mainstream treatment. Basic palliative care education
      programs for physicians not specializing in palliative care and other medical
      practitioners are bringing about the spread of basic palliative care in Japan,
      thus putting in place broad foundations for the practice of palliative care.
      Improving the quality of palliative care and providing specialized palliative
      care are essential in Japan. Future challenges are (i) the construction of a
      community palliative care network, (ii) fostering specialists in palliative care
      and (iii) the provision of high-quality palliative care and end-of-life care to
      patients with life-threatening illnesses that are not limited to cancer.

PMID- 23166388
TI  - Tumor aggressiveness and patient outcome in cancer of the pancreas assessed by
      dynamic 18F-FDG PET/CT.
AB  - This study aimed to assess the role of a quantitative dynamic PET model in
      pancreatic cancer as a potential index of tumor aggressiveness and predictor of
      survival. METHODS: Seventy-one patients with (18)F-FDG-avid adenocarcinoma of the
      pancreas before treatment were recruited, including 27 with localized tumors (11
      underwent pancreatectomy, and 16 had localized nonresectable tumors) and 44 with
      metastatic disease. Dynamic (18)F-FDG PET images were acquired over a 60-min
      period, followed by a whole-body PET/CT study. Quantitative data measurements
      were based on a 2-compartment model, and the following variables were calculated:
      VB (fractional blood volume in target area), K(1) and k(2) (kinetic membrane
      transport parameters), k(3) and k(4) (intracellular (18)F-FDG phosphorylation and
      dephosphorylation parameters, respectively), and (18)F-FDG INF (global (18)F-FDG
      influx). RESULTS: The single significant variable for overall survival (OS) in
      patients with localized disease was (18)F-FDG INF. Patients with a high (18)F-FDG
      INF (>0.033 min(-1)) had a median OS of 6 and 5 mo for nonresectable and resected
      tumors, respectively, versus 15 and 19 mo for a low (18)F-FDG INF in
      nonresectable and resected tumors, respectively (P < 0.04). In metastatic
      disease, multivariate analysis found VB, K(1), and k(3) to be significant
      variables for OS (P < 0.043, <0.031, and <0.009, respectively). Prognostic
      factors for OS in the entire group of patients that were significant at
      multivariate analysis were stage of disease, VB, K(1), and (18)F-FDG INF (P <
      0.00035, <0.03, <0.024, and <0.008, respectively). Median OS for all patients
      with a high (18)F-FDG INF, low VB, and high K(1) was 3 mo, as opposed to 14 mo in
      patients with a low (18)F-FDG INF, high VB, and low K(1) (P < 0.021),
      irrespective of stage and resectability. CONCLUSION: Quantitative (18)F-FDG
      kinetic parameters measured by dynamic PET in newly diagnosed pancreatic cancer
      correlated with the aggressiveness of disease. The (18)F-FDG INF was the single
      most significant variable for OS in patients with localized disease, whether
      resectable or not.

PMID- 23166389
TI  - Amyloid-beta imaging with Pittsburgh compound B and florbetapir: comparing
      radiotracers and quantification methods.
AB  - (11)C-Pittsburgh compound B ((11)C-PiB) and (18)F-florbetapir amyloid-beta
      (Abeta) PET radioligands have had a substantial impact on Alzheimer disease
      research. Although there is evidence that both radioligands bind to fibrillar
      Abeta in the brain, direct comparisons in the same individuals have not been
      reported. Here, we evaluated PiB and florbetapir in a retrospective convenience
      sample of cognitively normal older controls, patients with mild cognitive
      impairment, and patients with Alzheimer disease from the Alzheimer's Disease
      Neuroimaging Initiative (ADNI). METHODS: From the ADNI database, 32 participants
      were identified who had undergone at least 1 PiB study and subsequently underwent
      a florbetapir study approximately 1.5 y after the last PiB study. Cortical PiB
      and florbetapir retention was quantified using several different methods to
      determine the effect of preprocessing factors (such as smoothing and reference
      region selection) and image processing pipelines. RESULTS: There was a strong
      association between PiB and florbetapir cortical retention ratios (Spearman rho =
      0.86-0.95), and these were slightly lower than cortical retention ratios for
      consecutive PiB scans (Spearman rho = 0.96-0.98) made approximately 1.1 y apart.
      Cortical retention ratios for Abeta-positive subjects tended to be higher for PiB
      than for florbetapir images, yielding slopes for linear regression of florbetapir
      against PiB of 0.59-0.64. Associations between consecutive PiB scans and between
      PiB and florbetapir scans remained strong, regardless of processing methods such
      as smoothing, spatial normalization to a PET template, and use of reference
      regions. The PiB-florbetapir association was used to interconvert cutoffs for
      Abeta positivity and negativity between the 2 radioligands, and these cutoffs
      were highly consistent in their assignment of Abeta status. CONCLUSION: PiB and
      florbetapir retention ratios were strongly associated in the same individuals,
      and this relationship was consistent across several data analysis methods,
      despite scan-rescan intervals of more than a year. Cutoff thresholds for
      determining positive or negative Abeta status can be reliably transformed from
      PiB to florbetapir units or vice versa using a population scanned with both
      radioligands.

PMID- 23166390
TI  - Advances in understanding chromosome silencing by the long non-coding RNA Xist.
AB  - In female mammals, one of the two X chromosomes becomes genetically silenced to
      compensate for dosage imbalance of X-linked genes between XX females and XY
      males. X chromosome inactivation (X-inactivation) is a classical model for
      epigenetic gene regulation in mammals and has been studied for half a century. In
      the last two decades, efforts have been focused on the X inactive-specific
      transcript (Xist) locus, discovered to be the master regulator of X-inactivation.
      The Xist gene produces a non-coding RNA that functions as the primary switch for
      X-inactivation, coating the X chromosome from which it is transcribed in cis.
      Significant progress has been made towards understanding how Xist is regulated at
      the onset of X-inactivation, but our understanding of the molecular basis of
      silencing mediated by Xist RNA has progressed more slowly. A picture has,
      however, begun to emerge, and new tools and resources hold out the promise of
      further advances to come. Here, we provide an overview of the current state of
      our knowledge, what is known about Xist RNA and how it may trigger chromosome
      silencing.

PMID- 23166391
TI  - Importance of the matriline for genomic imprinting, brain development and
      behaviour.
AB  - Mammalian brain development commences during foeto-placental development and is
      strongly influenced by the epigenetic regulation of imprinted genes. The foetal
      placenta exerts considerable influence over the functioning of the adult maternal
      hypothalamus, and this occurs at the same time as the foetus itself is developing
      a hypothalamus. Thus, the action and interaction of two genomes in one
      individual, the mother, has provided a template for co-adaptive functions across
      generations that are important for maternal care and resource transfer, while co
      adaptively shaping the mothering capabilities of each subsequent generation. The
      neocortex is complex, enabling behavioural diversity and cultural learning such
      that human individuals are behaviourally unique. Retrotransposons may, in part,
      be epigenetic mediators of such brain diversity. Interestingly some imprinted
      genes are themselves retrotransposon-derived, and retrotransposon silencing by
      DNA methylation is thought to have contributed to the evolutionary origins of
      imprint control regions. The neocortex has evolved to be adaptable and sustain
      both short-term and long-term synaptic connections that underpin learning and
      memory. The adapted changes are not themselves inherited, but the predisposing
      mechanisms for such epigenetic changes are heritable. This provides each
      generation with the same ability to make new adaptations while constrained by a
      transgenerational knowledge-based predisposition to preserve others.

PMID- 23166392
TI  - DNA methylation dynamics during the mammalian life cycle.
AB  - DNA methylation is dynamically remodelled during the mammalian life cycle through
      distinct phases of reprogramming and de novo methylation. These events enable the
      acquisition of cellular potential followed by the maintenance of lineage
      restricted cell identity, respectively, a process that defines the life cycle
      through successive generations. DNA methylation contributes to the epigenetic
      regulation of many key developmental processes including genomic imprinting, X
      inactivation, genome stability and gene regulation. Emerging sequencing
      technologies have led to recent insights into the dynamic distribution of DNA
      methylation during development and the role of this epigenetic mark within
      distinct genomic contexts, such as at promoters, exons or imprinted control
      regions. Additionally, there is a better understanding of the mechanistic basis
      of DNA demethylation during epigenetic reprogramming in primordial germ cells and
      during pre-implantation development. Here, we discuss our current understanding
      of the developmental roles and dynamics of this key epigenetic system.

PMID- 23166393
TI  - Recent advancements in cloning by somatic cell nuclear transfer.
AB  - Somatic cell nuclear transfer (SCNT) cloning is the sole reproductive engineering
      technology that endows the somatic cell genome with totipotency. Since the first
      report on the birth of a cloned sheep from adult somatic cells in 1997, many
      technical improvements in SCNT have been made by using different epigenetic
      approaches, including enhancement of the levels of histone acetylation in the
      chromatin of the reconstructed embryos. Although it will take a considerable time
      before we fully understand the nature of genomic programming and totipotency, we
      may expect that somatic cell cloning technology will soon become broadly
      applicable to practical purposes, including medicine, pharmaceutical
      manufacturing and agriculture. Here we review recent progress in somatic cell
      cloning, with a special emphasis on epigenetic studies using the laboratory mouse
      as a model.

PMID- 23166394
TI  - Reprogramming DNA methylation in the mammalian life cycle: building and breaking
      epigenetic barriers.
AB  - In mammalian development, epigenetic modifications, including DNA methylation
      patterns, play a crucial role in defining cell fate but also represent epigenetic
      barriers that restrict developmental potential. At two points in the life cycle,
      DNA methylation marks are reprogrammed on a global scale, concomitant with
      restoration of developmental potency. DNA methylation patterns are subsequently
      re-established with the commitment towards a distinct cell fate. This
      reprogramming of DNA methylation takes place firstly on fertilization in the
      zygote, and secondly in primordial germ cells (PGCs), which are the direct
      progenitors of sperm or oocyte. In each reprogramming window, a unique set of
      mechanisms regulates DNA methylation erasure and re-establishment. Recent
      advances have uncovered roles for the TET3 hydroxylase and passive demethylation,
      together with base excision repair (BER) and the elongator complex, in
      methylation erasure from the zygote. Deamination by AID, BER and passive
      demethylation have been implicated in reprogramming in PGCs, but the process in
      its entirety is still poorly understood. In this review, we discuss the dynamics
      of DNA methylation reprogramming in PGCs and the zygote, the mechanisms involved
      and the biological significance of these events. Advances in our understanding of
      such natural epigenetic reprogramming are beginning to aid enhancement of
      experimental reprogramming in which the role of potential mechanisms can be
      investigated in vitro. Conversely, insights into in vitro reprogramming
      techniques may aid our understanding of epigenetic reprogramming in the germline
      and supply important clues in reprogramming for therapies in regenerative
      medicine.

PMID- 23166395
TI  - Epigenetic inheritance mediated by histone lysine methylation: maintaining
      transcriptional states without the precise restoration of marks?
AB  - 'Epigenetics' has been defined as the study of 'mitotically and/or meiotically
      heritable changes in gene function that cannot be explained by changes in DNA
      sequence'. Chromatin modifications are major carriers of epigenetic information
      that both reflect and affect the transcriptional states of underlying genes.
      Several histone modifications are key players that are responsible for classical
      epigenetic phenomena. However, the mechanisms by which cells pass their histone
      modifications to daughter cells through mitotic division remain to be unveiled.
      Here, we review recent progress in the field and conclude that epigenetic
      modifications are not precisely maintained at a near-mononucleosome level of
      precision. We also suggest that transcription repression may be maintained by a
      buffer system that can tolerate a certain degree of fluctuation in repressive
      histone modification levels. This buffer system protects the repressed genes from
      potential improper derepression triggered by chromatin modification-level
      fluctuation resulting from cellular events, such as the cell-cycle-dependent
      dilution of the chromatin modifications and local responses to environmental
      cues.

PMID- 23166396
TI  - Stem cell therapy: an exercise in patience and prudence.
AB  - In recent times, the epigenetic study of pluripotency based on cellular
      reprogramming techniques led to the creation of induced pluripotent stem cells.
      It has come to represent the forefront of a new wave of alternative therapeutic
      approaches in the field of stem cell therapy. Progress in drug development has
      saved countless lives, but there are numerous intractable diseases where curative
      treatment cannot be achieved through pharmacological intervention alone.
      Consequently, there has been an unfortunate rise in incidences of organ failures,
      degenerative disorders and cancers, hence novel therapeutic interventions are
      required. Stem cells have unique self-renewal and multilineage differentiation
      capabilities that could be harnessed for therapeutic purposes. Although a number
      of mature differentiated cells have been characterized in vitro, few have been
      demonstrated to function in a physiologically relevant context. Despite fervent
      levels of enthusiasm in the field, the reality is that other than the employment
      of haematopoietic stem cells, many other therapies have yet to be thoroughly
      proven for their therapeutic benefit and safety in application. This review shall
      focus on a discussion regarding the current status of stem cell therapy, the
      issues surrounding it and its future prospects with a general background on the
      regulatory networks underlying pluripotency.

PMID- 23166397
TI  - New insights into establishment and maintenance of DNA methylation imprints in
      mammals.
AB  - Fundamental to genomic imprinting in mammals is the acquisition of epigenetic
      marks that differ in male and female gametes at 'imprinting control regions'
      (ICRs). These marks mediate the allelic expression of imprinted genes in the
      offspring. Much has been learnt about the nature of imprint marks, the times
      during gametogenesis at which they are laid down and some of the factors
      responsible especially for DNA methylation. Recent work has revealed that
      transcription and histone modifications are critically involved in DNA
      methylation acquisition, and these findings allow us to propose rational models
      for methylation establishment. A completely novel perspective on gametic DNA
      methylation has emerged from epigenomic profiling. Far more differentially
      methylated loci have been identified in gametes than known imprinted genes, which
      leads us to revise the notion that methylation of ICRs is a specifically targeted
      process. Instead, it seems to obey default processes in germ cells, giving rise
      to distinct patterns of DNA methylation in sperm and oocytes. This new insight,
      together with the identification of proteins that preserve DNA methylation after
      fertilization, emphasizes the key role played by mechanisms that selectively
      retain differential methylation at imprinted loci during early development.
      Addressing these mechanisms will be essential to understanding the specificity
      and evolution of genomic imprinting.

PMID- 23166398
TI  - What obesity research tells us about epigenetic mechanisms.
AB  - The pathophysiology of obesity is extremely complex and is associated with
      extensive gene expression changes in tissues throughout the body. This situation,
      combined with the fact that all gene expression changes are thought to have
      associated epigenetic changes, means that the links between obesity and
      epigenetics will undoubtedly be vast. Much progress in identifying epigenetic
      changes induced by (or inducing) obesity has already been made, with candidate
      and genome-wide approaches. These discoveries will aid the clinician through
      increasing our understanding of the inheritance, development and treatment of
      obesity. However, they are also of great value for epigenetic researchers, as
      they have revealed mechanisms of environmental interactions with epigenetics that
      can produce or perpetuate a disease state. Here, we will review the evidence for
      four mechanisms through which epigenetics contributes to obesity: as downstream
      effectors of environmental signals; through abnormal global epigenetic state
      driving obesogenic expression patterns; through facilitating developmental
      programming and through transgenerational epigenetic inheritance.

PMID- 23166399
TI  - piRNA and spermatogenesis in mice.
AB  - Transposable elements and their fossil sequences occupy about half of the genome
      in mammals. While most of these selfish mobile elements have been inactivated by
      truncations and mutations during evolution, some copies remain competent to
      transpose and/or amplify, posing an ongoing genetic threat. To control such
      mutagenic sequences, host genomes have developed multiple layers of defence
      mechanisms, including epigenetic regulation and RNA silencing. Germ cells, in
      particular, employ the piwi-small RNA pathway, which plays a central and adaptive
      role in safeguarding the germline genome from retrotransposons. Recent studies
      have revealed that a class of developmentally regulated genes, which have long
      been implicated in germ cell specification and differentiation, such as vasa and
      tudor family genes, play key roles in the piwi pathway to suppress
      retrotransposons, indicating that the piwi-mediated genome protection is at the
      core of germline development. Furthermore, while the piwi system primarily
      operates post-transcriptionally at the RNA level, it also affects the epigenetics
      of cognate genome loci, offering an intriguing link between small RNAs and
      transcriptional control in mammals. In this review, we summarize our current
      understanding of the piwi pathway in mice, which is emerging as a fundamental
      component of spermatogenesis that ensures male fertility and genome integrity.

PMID- 23166400
TI  - Is there a role for endogenous retroviruses to mediate long-term adaptive
      phenotypic response upon environmental inputs?
AB  - Endogenous retroviruses (ERVs) are long terminal repeat-containing virus-like
      elements that have colonized approximately 10 per cent of the present day
      mammalian genomes. The intracisternal A particles (IAPs) are a class of ERVs that
      is currently highly active in the rodents. IAP elements can influence the
      transcription profile of nearby genes by providing functional promoter elements
      and modulating local epigenetic landscape through changes in DNA methylation and
      histone (H3K9) modifications. Despite the potential role for IAPs in gene
      regulation, the precise genomic locations where these elements are integrated are
      not well understood. To address this issue, we have identified more than 400
      novel IAP insertion sites within/near annotated genes by searching the murine
      genome, which suggests that the impact of IAP elements on local and/or global
      gene regulation could be more profound than was previously expected. On the basis
      of our independent analyses and already published reports, here we argue that
      IAPs and ERV elements in general could have an evolutionary role for modulating
      phenotypic plasticity upon environmental inputs, and that this could be mediated
      through specific stages of embryonic development such as placentation during
      which the epigenetic constraints on IAP elements are partially relaxed.

PMID- 23166401
TI  - The origin and evolution of genomic imprinting and viviparity in mammals.
AB  - Genomic imprinting is widespread in eutherian mammals. Marsupial mammals also
      have genomic imprinting, but in fewer loci. It has long been thought that genomic
      imprinting is somehow related to placentation and/or viviparity in mammals,
      although neither is restricted to mammals. Most imprinted genes are expressed in
      the placenta. There is no evidence for genomic imprinting in the egg-laying
      monotreme mammals, despite their short-lived placenta that transfers nutrients
      from mother to embryo. Post natal genomic imprinting also occurs, especially in
      the brain. However, little attention has been paid to the primary source of
      nutrition in the neonate in all mammals, the mammary gland. Differentially
      methylated regions (DMRs) play an important role as imprinting control centres in
      each imprinted region which usually comprises both paternally and maternally
      expressed genes (PEGs and MEGs). The DMR is established in the male or female
      germline (the gDMR). Comprehensive comparative genome studies demonstrated that
      two imprinted regions, PEG10 and IGF2-H19, are conserved in both marsupials and
      eutherians and that PEG10 and H19 DMRs emerged in the therian ancestor at least
      160 Ma, indicating the ancestral origin of genomic imprinting during therian
      mammal evolution. Importantly, these regions are known to be deeply involved in
      placental and embryonic growth. It appears that most maternal gDMRs are always
      associated with imprinting in eutherian mammals, but emerged at differing times
      during mammalian evolution. Thus, genomic imprinting could evolve from a defence
      mechanism against transposable elements that depended on DNA methylation
      established in germ cells.

PMID- 23166404
TI  - Mammalian epigenetics in biology and medicine.

PMID- 23166403
TI  - Embryo manipulation via assisted reproductive technology and epigenetic asymmetry
      in mammalian early development.
AB  - The early stage of mammalian development from fertilization to implantation is a
      period when global and differential changes in the epigenetic landscape occur in
      paternally and maternally derived genomes, respectively. The sperm and egg DNA
      methylation profiles are very different from each other, and just after
      fertilization, only the paternally derived genome is subjected to genome-wide
      hydroxylation of 5-methylcytosine, resulting in an epigenetic asymmetry in
      parentally derived genomes. Although most of these differences are not present by
      the blastocyst stage, presumably due to passive demethylation, the maintenance of
      genomic imprinting memory and X chromosome inactivation in this stage are of
      critical importance for post-implantation development. Zygotic gene activation
      from paternally or maternally derived genomes also starts around the two-cell
      stage, presumably in a different manner in each of them. It is during this period
      that embryo manipulation, including assisted reproductive technology, is normally
      performed; so it is critically important to determine whether embryo manipulation
      procedures increase developmental risks by disturbing subsequent gene expression
      during the embryonic and/or neonatal development stages. In this review, we
      discuss the effects of various embryo manipulation procedures applied at the
      fertilization stage in relation to the epigenetic asymmetry in pre-implantation
      development. In particular, we focus on the effects of intracytoplasmic sperm
      injection that can result in long-lasting transcriptome disturbances, at least in
      mice.

PMID- 23166402
TI  - Epigenetic regulation in pluripotent stem cells: a key to breaking the epigenetic
      barrier.
AB  - The differentiation and reprogramming of cells are accompanied by drastic changes
      in the epigenetic profiles of cells. Waddington's classical model clearly
      describes how differentiating cells acquire their cell identity as the
      developmental potential of an individual cell population declines towards the
      terminally differentiated state. The recent discovery of induced pluripotent stem
      cells as well as of somatic cell nuclear transfer provided evidence that the
      process of differentiation can be reversed. The identity of somatic cells is
      strictly protected by an epigenetic barrier, and these cells acquire pluripotency
      by breaking the epigenetic barrier by reprogramming factors such as Oct3/4, Sox2,
      Klf4, Myc and LIN28. This review covers the current understanding of the spatio
      temporal regulation of epigenetics in pluripotent and differentiated cells, and
      discusses how cells determine their identity and overcome the epigenetic barrier
      during the reprogramming process.

PMID- 23166405
TI  - Buffering boys and boosting girls: The protective and promotive effects of Early
      Head Start for children's expressive language in the context of parenting stress.
AB  - Children's characteristics, including gender, influence their development by
      eliciting differential responses from their environments, and by influencing
      differential responses to their environments. Parenting-related stress,
      associated with poverty environments, negatively influences children's language,
      likely through its impact on parent-child interactions, but may impact boys' and
      girls' development differently. Early intervention represents one tool for
      supporting development in at-risk toddlers, but gender-differences in effects of
      intervention are rarely described. The current studies assessed the effects of
      Early Head Start (EHS) on children's productive vocabulary in the context of
      parenting stress and examined gender differences in program effects on vocbulary.
      Data were from the national EHS Research and Evaluation (EHSRE) study (Study 1, N
      = 3,001), and from a dataset associated with one EHSRE site (Study 2, N = 146)
      where additional data on productive vocabulary were collected. Study 1 found that
      at 24 months of age, the EHS program protected girls' productive vocabulary from
      the negative effects of parenting stress, but had little impact on boys'
      vocabulary. In Study 2, the local EHS site promoted girls' vocabulary development
      over time from 14 to 36 months despite the negative effects of parenting stress,
      and protected boys' vocabulary from the negative parenting stress effects. These
      results suggest differential ways in which at-risk toddlers are affected by early
      intervention.

PMID- 23166406
TI  - Health care plan for hydrogen fluoride spill, Gumi, Korea.

PMID- 23166407
TI  - Effect of additional brief counselling after periodic health examination on
      motivation for health behavior change [corrected].
AB  - This study was to evaluate the effect of additional brief counseling by a primary
      care physician on lifestyle modification of examinees after a periodic health
      examination. 1,000 participants of the 2007 Korean national health screening
      program were asked to note any variation in their health behavior after
      participating in the screening program. The degree of comprehensive motivation
      for lifestyle modification was assessed in terms of stages of health behavior
      change. We calculated odds ratio of positive change (enhanced stage of change)
      with multiple logistic regression analysis and age-adjusted proportion of
      positive changers. Of 989 respondents, 486 and 503 received the basic and
      additional programs, respectively. Additional group were more likely to be
      positive changer than basic group (adjusted OR 1.78; 95% CI 1.19-2.65), and this
      was more prominent in older age group (adjusted OR 2.38, 95% CI 1.23-4.58). The
      age-adjusted proportions of positive changers were 22.7% (95% CI, 17.9-28.3) and
      36.2% (95% CI, 30.4-42.4) in the basic and additional groups, respectively (P <
      0.001). The additional consultation led to improvements in the stage of health
      behavior change after the health examination. Thus, such a consultation should be
      considered when designing a health-screening program.

PMID- 23166408
TI  - Identifying genetic susceptibility to sensitization to cephalosporins in health
      care workers.
AB  - Exposure to cephalosporins could cause occupational allergic diseases in health
      care workers (HCWs). We evaluated the prevalence of serum specific IgE and IgG
      antibodies to cephalosporin-human serum albumin (HSA) conjugate and to identify
      potential genetic risk factors associated with sensitization to cephalosporins in
      exposed HCWs. The study population consisted of 153 HCWs who had been exposed to
      antibiotics in a single university hospital and 86 unexposed healthy controls. A
      questionnaire survey of work-related symptoms (WRS) was administered. A skin
      prick test (SPT) was performed, and serum-specific IgE and IgG antibodies to 3
      commonly prescribed cephalosporins were measured by ELISA. Four single-nucleotide
      polymorphisms of the candidate genes related to IgE sensitization were genotyped.
      The prevalence of WRS to cephalosporins was 2.6%. The prevalence rates of serum
      specific IgE and IgG antibodies to cephalosporins were 20.3% and 14.7%,
      respectively. The FcepsilonR1beta-109T > C polymorphism was significantly
      associated with IgE sensitization to cephalosporins in HCWs (P = 0.036, OR =
      3.553; CI, 1.324-9.532). The in vitro functional assay demonstrated that the T
      allele of FcepsilonR1beta-109T had greater promoter activity than did the C
      allele (P < 0.001). The FcepsilonR1beta-109T > C polymorphism may be a potential
      genetic risk factor for increased IgE sensitization to cephalosporins.

PMID- 23166409
TI  - Human amniotic fluid stem cell-derived muscle progenitor cell therapy for stress
      urinary incontinence.
AB  - The most promising treatment for stress urinary incontinence can be a cell
      therapy. We suggest human amniotic fluid stem cells (hAFSCs) as an alternative
      cell source. We established the optimum in vitro protocol for the differentiation
      from hAFSCs into muscle progenitors. These progenitors were transplanted into the
      injured urethral sphincter and their therapeutic effect was analyzed. For the
      development of an efficient differentiation system in vitro, we examined a
      commercial medium, co-culture and conditioned medium (CM) systems. After being
      treated with CM, hAFSCs were effectively developed into a muscle lineage. The
      progenitors were integrated into the host urethral sphincter and the host cell
      differentiation was stimulated in vivo. Urodynamic analysis showed significant
      increase of leak point pressure and closing pressure. Immunohistochemistry
      revealed the regeneration of circular muscle mass with normal appearance.
      Molecular analysis observed the expression of a larger number of target markers.
      In the immunogenicity analysis, the progenitor group had a scant CD8 lymphocyte.
      In tumorigenicity, the progenitors showed no teratoma formation. These results
      suggest that hAFSCs can effectively be differentiated into muscle progenitors in
      CM and that the hAFSC-derived muscle progenitors are an accessible cell source
      for the regeneration of injured urethral sphincter.

PMID- 23166410
TI  - Epidemiological and clinical characteristics of community-acquired severe sepsis
      and septic shock: a prospective observational study in 12 university hospitals in
      Korea.
AB  - A prospective multicenter observational study was performed to investigate the
      epidemiology and outcomes of community-acquired severe sepsis and septic shock.
      Subjects included 1,192 adult patients admitted to the 22 participating intensive
      care units (ICUs) of 12 university hospitals in the Korean Sepsis Registry System
      from April, 2005 through February, 2009. Male accounted for 656 (55%) patients.
      Mean age was 65.0 +/- 14.2 yr. Septic shock developed in 740 (62.1%) patients.
      Bacteremia was present in 422 (35.4%) patients. The 28-day and in-hospital
      mortality rates were 23.0% and 28.0%, respectively. Men were more likely to have
      comorbid illnesses and acute organ dysfunctions, and had higher mortality and
      clinical severity compared to women. While respiratory sources of sepsis were
      common in men, urinary sources were predominant in women. In the multivariate
      logistic regression analysis, cancer (odds ratio 1.89; 95% confidence interval
      1.13-3.17), urinary tract infection (0.25; 0.13-0.46), APACHE II score (1.05;
      1.02-1.09), SOFA score on day 1 (1.13; 1.06-1.21) and metabolic dysfunction
      (2.24, 1.45-3.45) were independent clinical factors for gender-related in
      hospital mortality. This study provided epidemiological and clinical
      characteristics of community-acquired severe sepsis and septic shock in ICUs in
      Korea, and demonstrated the impact of clinical factors on gender difference in
      mortality.

PMID- 23166411
TI  - Phylogenetic analysis of the 56-kDa type-specific protein genes of Orientia
      tsutsugamushi in Central Korea.
AB  - There are several antigenic variants of Orientia tsutsugamushi. The 56-kDa type
      specific antigen (TSA) is responsible for the antigenic variation. Nucleotide
      sequences of the 56-kDa TSA obtained from 44 eschar samples of Korean scrub
      typhus patients and from 40 representative strains retrieved from the GenBank
      database were analyzed phylogenetically. Clinical patient data were assessed
      based on the genotyping results. Of the 44 nucleotide sequences, 32 (72.7%)
      clustered with the Boryong genotype, which is the major genotype in Korea. Eleven
      nucleotide sequences (25%) clustered with the Kawasaki genotype, not identified
      in Korea until 2010. One nucleotide sequence was consistent with the Karp
      genotype. The clinical course of the patients infected with each genotype showed
      no differences. Diagnostic performance of the immunofluorescence assay (IFA)
      using the 56-kDa TSA from Gilliam, Karp and Boryong as test antigens were not
      different for the Boryong and Kawasaki genotypes. Although Boryong is still the
      predominant genotype, the results suggest that Kawasaki genotype is quite
      prevalent in Chungbuk province of Korea.

PMID- 23166412
TI  - Cord blood cellular proliferative response as a predictive factor for atopic
      dermatitis at 12 months.
AB  - Since the risk of developing allergic disease increases in individuals exposed to
      allergens previously, even during the neonatal period, the immunologic status of
      a fetus may be important in the subsequent development of allergy. We evaluated
      the fetal factors to predict atopic dermatitis (AD) at 12 months in 412 infants
      of a COhort for Childhood Origin of Asthma and Allergic Diseases (COCOA) in the
      general Korean population. Cord blood mononuclear cells (CBMCs) were stimulated
      with ovalbumin and phytohemagglutinin and cellular proliferative response and
      concentrations of interleukin-13 and interferon-gamma, were measured. The risk of
      developing AD was greater in boys than girls (OR 1.97, 95% CI 1.26-3.09), infants
      delivered by cesarean section than vaginally (OR 1.93, 95% CI 1.14-3.26) and
      infants with than without parental history of AD (OR 2.34, 95% CI 1.29-4.24). The
      CBMC proliferative response to phytohemagglutinin stimulation was higher in
      infants with than without AD (P = 0.048), but no difference was observed in
      ovalbumin-stimulated cells (P = 0.771). Risk factors for the development of AD at
      12 months include male gender, delivery by cesarean section and parental history
      of AD. Increased CBMC proliferative response to phytohemagglutinin stimulation
      may predict the development of AD at 12 months.

PMID- 23166413
TI  - Quality of life and disease severity are correlated in patients with atopic
      dermatitis.
AB  - Quantification of quality of life (QOL) related to disease severity is important
      in patients with atopic dermatitis (AD), because the assessment provides
      additional information to the traditional objective clinical scoring systems. To
      document the impact of AD on QOL for both children and adults as well as to
      quantify the relationship with disease severity, QOL assessments were performed
      over a 6-month period on 415 patients with AD. A questionnaire derived from the
      Infants' Dermatitis Quality of Life Index (IDQOL), the Children's Dermatology
      Life Quality Index (CDLQI) and the Dermatology Life Quality Index (DLQI) was used
      to determine the QOL for 71 infants, 197 children and 147 adults, respectively.
      To measure AD severity, both the Rajka & Langeland scoring system and the Scoring
      of Atopic Dermatitis (SCORAD) index were used. The mean scores were as follows:
      7.7 +/- 5.5 for IDQOL, 6.6 +/- 6.3 for CDLQI, and 10.7 +/- 7.9 for DLQI. In
      conclusion, these QOL scores are correlated with AD severity scores as estimated
      by the Rajka & Langeland severity score and the SCORAD. The outcome of the QOL
      instruments in this study demonstrates that atopic dermatitis of both children
      and adults affects their QOL.

PMID- 23166414
TI  - Association of Toll-like receptor 2 polymorphisms with papillary thyroid cancer
      and clinicopathologic features in a Korean population.
AB  - Toll-like receptors (TLRs) single nucleotide polymorphisms (SNPs) were analyzed
      in patients with papillary thyroid cancer (PTC; n = 133) and their
      clinicopathologic features and age-matched controls (n = 321) using direct
      sequencing. PTC patients were divided into subgroups according to size, number,
      location, extrathyroidal invasion and lymph node metastasis. The two SNPs of TLR2
      gene were not associated with the development of PTC. In clinical analysis, two
      SNPs were associated with location of cancer (rs3804099, P = 0.032, OR, 0.52; 95%
      CI, 0.28-0.96 in log-additive model; rs3804100, P = 0.039, OR, 0.46, 95% CI, 0.22
      0.96 in codominant1 model; P = 0.018, OR, 0.42, 95% CI, 0.21-0.87 in dominant
      model; P = 0.011, OR, 0.46, 95% CI, 0.25-0.85 in log-additive model). The allele
      frequencies of two SNPs also showed significant associations with location of
      cancer (rs3804099, P = 0.046, OR, 0.57, 95% CI, 0.33-0.99 and rs3804100, P =
      0.019, OR = 0.52, 95% CI = 0.30-0.90). However, two SNPs were not associated with
      the clinicopathologic features of PTC. It is suggested that TLR2 polymorphisms
      may contribute to the clinicopathologic features of PTC, especially the PTC in
      both lobes.

PMID- 23166415
TI  - Safety and efficacy of overlapping homogenous drug-eluting stents in patients
      with acute myocardial infarction: results from Korea Acute Myocardial Infarction
      Registry.
AB  - The aim of this study was to compare safety and efficacy of 4 homogenous
      overlapping drug-eluting stents (DES) in acute myocardial infarction (AMI)
      patients. We selected 1,349 consecutive patients (62.1 +/- 14.9 yr, 69.4% male)
      who received homogenous overlapping DESs in diffuse de novo coronary lesions from
      Korea Acute Myocardial Infarction Registry from April 2006 through September
      2010. They were divided into 4 groups based on type of DES implanted - Paclitaxel
      (PES), Sirolimus (SES), Zotarolimus (ZES) and Everolimus (EES)-eluting stents.
      Primary endpoint was 12-month MACE. We also studied EES versus other DESs (PES +
      SES + ZES). Mean stent length was 26.2 +/- 7.5 mm and mean stent diameter was 3.1
      +/- 0.4 mm. Average number of stents used per vessel was 2.2 +/- 0.5. Incidence
      of major adverse cardiac events (MACE) in PES, SES, ZES, and EES groups were
      9.5%, 9.2%, 7.5%, and 3.8%, respectively (P = 0.013). In EES group, overall MACE
      and repeat revascularization were lowest, and no incidence of stent thrombosis
      was observed. Non-fatal MI was highest in PES, almost similar in SES and EES with
      no incidence in ZES group (P = 0.044). Cox proportional hazard analysis revealed
      no differences in the incidence of primary endpoint (P = 0.409). This study shows
      no significant differences in 12-month MACE among 4 groups.

PMID- 23166417
TI  - Onodera's prognostic nutritional index as a risk factor for mortality in
      peritoneal dialysis patients.
AB  - The aim of this study was to evaluate the clinical relevance and usefulness of
      the Onodera's prognostic nutritional index (OPNI) as a prognostic and nutritional
      indicator in peritoneal dialysis (PD) patients. Patients were divided into 3
      groups based on the initial OPNI score: group A (n = 186, < 40), group B (n =
      150, 40-45), and group C (n = 186, > 45). Group A was associated with a higher
      grade according to the Davies risk index than the other groups. Serum creatinine
      and albumin levels, total lymphocyte count, and fat mass increased with an
      increase in OPNI. According to the edema index, the correlation coefficient for
      OPNI was -0.284 and for serum albumin was -0.322. Similarly, according to the C
      reactive protein (CRP), the correlation coefficient for OPNI was -0.117 and for
      serum albumin was -0.169. Multivariate analysis adjusted for age, Davies risk
      index, CRP, and edema index revealed that the hazard ratios for low OPNI, serum
      albumin, and CRP were 1.672 (P = 0.003), 1.308 (P = 0.130), and 1.349 (P =
      0.083), respectively. Our results demonstrate that the OPNI is a simple method
      that can be used for predicting the nutritional status and clinical outcome in PD
      patients.

PMID- 23166416
TI  - Comparison of clinical and imaging characteristics and outcomes between provoked
      and unprovoked acute pulmonary embolism in Koreans.
AB  - This study was performed to compare clinical and imaging parameters and prognosis
      of unprovoked pulmonary embolism (PE), provoked PE with reversible risk factors
      (provoked-rRF), and provoked PE with irreversible risk factors (provoked-iRF) in
      Koreans. Three hundred consecutive patients (mean age, 63.6 +/- 15.0 yr; 42.8%
      male) diagnosed with acute PE were included. The patients were classified into 3
      groups; unprovoked PE, provoked-rRF, and provoked-iRF; 43.7%, 14.7%, and 41.7%,
      respectively. We followed up the patients for 25.4 +/- 33.7 months. Composite
      endpoint was all-cause mortality and recurrent PE. The provoked-iRF group had
      significantly higher all-cause mortality, mortality from PE and recurrent PE than
      the unprovoked and provoked-rRF groups (P < 0.001, P < 0.001, and P = 0.034,
      respectively). Prognostic factors of composite endpoint in the unprovoked group
      were high creatinine (> 1.2 mg/dL; P < 0.001; hazard ratio [HR], 4.735; 95%
      confidence interval [CI], 1.845-12.152), C-reactive protein (CRP; > 5 mg/L; P =
      0.002; HR, 5.308; 95% CI, 1.824-15.447) and computed tomography (CT) obstruction
      index (P = 0.034; HR, 1.090; 95% CI, 1.006-1.181). In conclusion, provoked-iRF
      has a poorer prognosis than unprovoked PE and provoked-rRF. Renal insufficiency,
      high CRP, and CT obstruction index are poor prognostic factors in unprovoked PE.

PMID- 23166418
TI  - Determinants of brachial-ankle pulse wave velocity in normotensive young adults
      with type 2 diabetes mellitus.
AB  - Brachial-ankle pulse wave velocity (baPWV) is simple, noninvasive method which
      correlates well with arterial stiffness. Herein, we assessed the determinants of
      baPWV in normotensive young adults with type 2 diabetes. We retrospectively
      enrolled 103 consecutive type 2 diabetic patients aged between 30 and 39 yr who
      measured baPWV with noninvasive pulse wave analyzer. The anthropometric
      parameters, blood pressure, pulse rate, fasting plasma glucose, fasting insulin,
      fasting C-peptide, HbA1c, lipid profile, hs-CRP, albuminuria status, AST/ALT,
      gamma-GTP were checked concurrently. Also, we investigated history of smoking,
      alcohol drinking and medications by questionnaire. We found that maximal baPWV
      was positively correlated with mean blood pressure (r = 0.404, P < 0.001), heart
      rate (r = 0.285, P = 0.004), AST (r = 0.409, P < 0.001), ALT (r = 0.329, P =
      0.001), gamma-GTP (r = 0.273, P = 0.006), Urine albumin/creatinine ratio (r =
      0.321, P = 0.003). By multiple linear regression, mean blood pressure and heart
      rate were significantly associated with maximal baPWV in male and total group. In
      female group, mean blood pressure was the only variable associated with maximal
      baPWV. These factors can be surrogate markers of arterial stiffness in this
      population.

PMID- 23166419
TI  - The dipeptidyl peptidase-4 inhibitor sitagliptin improves vascular endothelial
      function in type 2 diabetes.
AB  - The vascular endothelial function is impaired in the very early stage of
      atherosclerosis in diabetic patients. The goal of this study was to identify the
      mechanism underlying the improvement in vascular endothelial function by
      sitagliptin in type 2 diabetes mellitus patients. This study was an open-labeled
      prospective observational single arm trial. Forty patients were treated with 50
      mg of sitagliptin once daily for 12-weeks. The flow-mediated dilation (FMD) and
      plasma adiponectin were measured at baseline and 12 weeks after initiating
      treatment. The %FMD was significantly increased after treatment (4.13 +/- 1.59 vs
      5.12 +/- 1.55, P < 0.001), whereas the nitroglycerin-mediated dilation (NMD) did
      not change. The plasma adiponectin levels significantly increased (13.0 +/- 11.3
      vs 14.3 +/- 12.8, P < 0.001). The changes in the FMD were significantly
      correlated with those of the plasma adiponectin (r = 0.322, P < 0.05). A
      multivariate linear regression analysis demonstrated that the improvement in the
      FMD is associated with the plasma adiponectin (P < 0.05). The treatment of type 2
      diabetes mellitus patients with sitagliptin reverses vascular endothelial
      dysfunction, as evidenced by increase in the FMD, and improvement of the
      adiponectin levels.

PMID- 23166420
TI  - Behavioral and healthcare-associated risk factors for chronic hepatitis C virus
      infection in Korea.
AB  - The risk factors related to hepatitis C virus (HCV) infection showed geographic
      and temporal differences. We investigated HCV-related risk factors in Korea where
      intravenous drug use (IVDU) is uncommon. The HCV-related risk factors were
      investigated in a prospective, multicenter chronic HCV cohort (n = 711) using a
      standardized questionnaire in four university hospitals. The results were
      compared with those of 206 patients with chronic liver diseases not related to
      either of HCV or hepatitis B virus infection (comparison group). The IVDU was
      found in 3.9% and remote blood transfusion (>= 20 yr ago) in 18.3% in HCV cohort
      group, while that in comparison group was in none and 5.3%, respectively. In a
      multivariate logistic analysis, transfusion in the remote past (odds ratio [OR],
      2.99), needle stick injury (OR, 4.72), surgery (OR, 1.89), dental procedures (OR,
      2.96), tattooing (OR, 2.07), and multiple sexual partners (2-3 persons; OR, 2.14,
      >= 4 persons; OR, 3.19), were independent risk factors for HCV infection. In
      conclusion, the major risk factors for HCV infection in Korea are mostly related
      to conventional or alterative healthcare procedures such as blood transfusion in
      the remote past, needle stick injury, surgery, dental procedure, and tattooing
      although multiple sex partners or IVDU plays a minor role.

PMID- 23166421
TI  - Successful treatment of primary central nervous system lymphoma without
      irradiation in children: single center experience.
AB  - Primary CNS lymphoma (PCNSL) is a very uncommon disease in children, and usually
      treated by chemotherapy, combined with focal or craniospinal radiotherapy (RT).
      However, adverse effects of RT are a concern. We evaluated the outcomes of
      childhood PCNSL, treated with systemic and intrathecal chemotherapy, but without
      RT. For fifteen years, six patients among 175 of non-Hodgkin lymphoma were
      diagnosed as PCNSL in Seoul National University Children's Hospital and we
      analyzed their medical records retrospectively. Their male:female ratio was 5:1,
      and median age was 10.1 yr. The primary sites were the sellar area in three
      patients, parietal area in one, cerebellum in one, and multiple areas in one.
      Their pathologic diagnoses were diffuse large B-cell lymphoma in three patients,
      Burkitt lymphoma in two, and undifferentiated B-cell lymphoma in one. Five were
      treated with the LMB96 treatment protocol, and one was treated with the CCG-106B
      protocol. None had RT as a first-line treatment. One patient had a local relapse
      and received RT and salvage chemotherapy, without success. No patient had
      treatment-related mortality. Their estimated 5-yr event-free and overall survival
      rates were both 83.3%. In conclusion, PCNSL is a rare disease in childhood, but
      successfully treated by chemotherapy without RT.

PMID- 23166422
TI  - Adolescent build plotting on body composition chart and the type of diabetes
      mellitus.
AB  - Although the prevalence of type 2 diabetes is increasing, there are cases
      difficult to categorize into certain type in pediatric diabetic patients. The
      aims of this study were to detect and choose a proper treatment modality for
      atypical cases of diabetes mellitus, using the body composition chart. We
      conducted a retrospective study from August 2005 to 2012 with patients who
      visited Konkuk University Medical Center, and were diagnosed with diabetes
      mellitus. The medical records were reviewed for the anthropometric data and
      indices of body composition. The subjects were grouped by the type of diabetes
      and gender. We constructed a body composition chart plotting fat free mass index
      and fat mass index (FMI). Body mass index and all body composition indices were
      higher in type 2 diabetes, in each gender in analysis with Mann-Whitney test.
      Significant determinant of diabetes type was revealed as FMI and contributing
      factors on FMI were analyzed with regression analysis. Six atypical cases were
      identified by a body composition chart including non-obese type 2 diabetes
      showing suboptimal growth with lower BMI related to relatively lower insulin
      secretion and type 1 diabetes with insulin resistance resulted from obesity. Body
      composition chart analysis might be useful in characterization of diabetes type
      and detection of atypical cases and early adjustment of diabetes management
      strategy.

PMID- 23166423
TI  - Localization value of magnetoencephalography interictal spikes in adult
      nonlesional neocortical epilepsy.
AB  - Few studies have included magnetoencephalography (MEG) when assessing the
      diagnostic value of presurgical modalities in a nonlesional epilepsy population.
      Here, we compare single photon emission computed tomography (SPECT), positron
      emission tomography (PET), video-EEG (VEEG), and MEG, with intracranial EEG
      (iEEG) to determine the value of individual modalities to surgical decisions. We
      analyzed 23 adult epilepsy patients with no abnormal MRI findings who had
      undergone surgical resection. Localization of individual presurgical tests was
      determined for hemispheric and lobar locations based on visual analysis. Each
      localization result was compared with the ictal onset zone (IOZ) defined by using
      iEEG. The highest to the lowest hemispheric concordance rates were MEG (83%) >
      ictal VEEG (78%) > PET (70%) > ictal SPECT (57%). The highest to lowest lobar
      concordance rates were ictal VEEG = MEG (65%) > PET (57%) > ictal SPECT (52%).
      Statistical analysis showed MEG to have a higher hemispheric concordance than
      that of ictal SPECT (P = 0.031). We analyzed the effects of MEG clustered-area
      resection on surgical outcome. Patients who had resection of MEG clusters showed
      a better surgical outcome than those without such resection (P = 0.038). It is
      suggested that MEG-based localization had the highest concordance with the iEEG
      defined IOZ. Furthermore, MEG cluster resection has prognostic significance in
      predicting surgical outcome.

PMID- 23166424
TI  - Relationship between irritable bowel syndrome, worry and stress in adolescent
      girls.
AB  - The aim of this study is to investigate prevalence of irritable bowel syndrome
      (IBS) among adolescents and difference in worry and stress between normal and IBS
      groups. Questionnaire survey was conducted at a girl's middle and high school.
      Students from seventh to eleventh grade participated in the examination on Rome
      II criteria, lifestyle and dietary habits. Worry and stress were measured with
      the Korean version Penn State Worry Questionnaire-Children and the Korean version
      Brief Encounter Psychosocial Instrument. Worry score was significantly higher in
      the IBS group (22.07 +/- 9.38, P < 0.001) than in the normal group (18.65 +/-
      8.99) and was higher in high school students than in middle school students (P =
      0.02). Stress score also was higher in the IBS group than in the normal group (P
      < 0.001) and was higher in the high school girls than in the middle school ones
      (P = 0.04). Of all the lifestyle factors influencing IBS preference for fatty
      foods, preference for salty foods, drinking alcohol and sleeping for less than
      six hours a day were found to be significant. Worry and stress seem to be
      associated with IBS symptoms. The findings of this study draw a clue that less
      worry and stress will help decrease IBS symptoms.

PMID- 23166425
TI  - Inhalation therapy of calcitonin relieves osteoarthritis of the knee.
AB  - This study was conducted to determine if nasal salmon calcitonin has additional
      beneficial effects on clinical symptoms, serum NO, IL-1beta, matrix
      metalloproteinase 3, urinary C-terminal telopeptide type II collagen (CTX-II)
      levels and MRI findings in knee osteoarthritis (OA) when used concomitantly with
      exercise therapy. Fifty female patients with knee OA were randomized into two
      groups. The first group (n = 30) received 200 IU/day nasal salmon calcitonin and
      a home exercise program; the second group (n = 20) received a home exercise
      program for 6 months. Compared with baseline,while significant improvements were
      observed in visual analogue scale (VAS), WOMAC pain, physical function scores, 20
      m walking time (P < 0.001) and WOMAC stiffness score (P = 0.041) in the first
      group, walking and resting VAS, and WOMAC physical function scores were improved
      (P = 0.029) in the second group after treatment. Significantly increased levels
      of serum NO and urinary CTX-II (P < 0.001) and significant improvements in the
      area of medial femoral condyle (P < 0.05) were noted only in the first group.
      There were significant differences in VAS activation values (P = 0.032) and NO
      levels (P < 0.001) in the favor of the first group. In conclusion, nasal salmon
      calcitonin may have possible chondroprotective effects besides its known effects
      on symptoms in patients with knee OA.

PMID- 23166426
TI  - Analgesic effects of dexmedetomidine in vincristine-evoked painful neuropathic
      rats.
AB  - Dexmedetomidine, which is a selective alpha2-adrenoceptor agonist, was recently
      introduced into clinical practice for its analgesic properties. The purpose of
      this study was to evaluate the effects of dexmedetomidine in a vincristine-evoked
      neuropathic rat models. Sprague-Dawley rats were injected intraperitoneally with
      vincristine or saline (0.1 mg/kg/day) using a 5-day-on, 2-day-off schedule for 2
      weeks. Saline and dexmedetomidine (12.5, 25, 50, and 100 ug/kg) were injected to
      rats developed allodynia 14 days after vincristine injection, respectively. We
      evaluated allodynia at before, 15, 30, 60, 90, 120, 180, and 240 min, and 24 hr
      after intraperitoneal drug (normal saline or dexmedetomidine) injection. Saline
      treatment did not show any differences for all the allodynia. Maximal paw
      withdrawal thresholds to mechanical stimuli were 3.0 +/- 0.4, 9.1 +/- 1.9, 13.0
      +/- 3.6, 16.6 +/- 2.4, and 24.4 +/- 1.6 g at saline, 12.5, 25, 50, and 100 ug/kg
      dexmedetomidine injection, respectively. Minimal withdrawal frequency to cold
      stimuli were 73.3 +/- 4.2, 57.1 +/- 6.8, 34.3 +/- 5.7, 20.0 +/- 6.2, and 14.3 +/-
      9.5 g at saline, 12.5, 25, 50, and 100 ug/kg dexmedetomidine injection,
      respectively. Dexmedetomidine shows a dose-dependent antiallodynic effect on
      mechanical and cold stimuli in vincristine-evoked neuropathic rat models (P <
      0.05).

PMID- 23166427
TI  - The incidence, causes, and prognostic significance of new-onset thrombocytopenia
      in intensive care units: a prospective cohort study in a Korean hospital.
AB  - This study was designed to investigate the incidence, causes, and outcomes of new
      onset thrombocytopenia (NOT) in Korean intensive care units (ICUs). A prospective
      cohort study was conducted in medical ICUs of Samsung Medical Center between
      August 2010 and February 2011. All newly admitted patients were included if they
      stayed in the ICU for more than 48 hr and did not have thrombocytopenia upon
      admission. A total of 186 patients were included. NOT developed in 37.1%. Most
      common cause of NOT was sepsis with disseminated intravascular coagulation
      (66.7%), followed by drug-induced thrombocytopenia (18.8%), and heparin-induced
      thrombocytopenia (2.9%). IgG-specific antibody to platelet factor 4/heparin was
      positive in 2.4% among patients treated with heparin, and thrombosis occurred in
      two patients. Twenty eight-day mortality was higher in patients that developed
      NOT compared to those that did not develop NOT (39.1% vs 12%, P < 0.001). NOT
      increased the odds ratio of 28-day mortality and was an independent risk factor
      for mortality (OR 3.52; 95% CI 1.32-9.38; P = 0.012). In conclusion, NOT is
      common and is an independent risk factor for mortality in Korean ICU patients.
      Therefore, clinicians should make every effort to correct the causes of NOT.

PMID- 23166428
TI  - Familial Mediterranean fever: the first adult case in Korea.
AB  - Familial Mediterranean fever (FMF) is known to be a genetic disorder that
      prevalent among populations surrounding the Mediterranean Sea. Since
      Mediterranean fever gene (MEFV) was discovered at 1997, some cases have been
      reported in countries not related or close to this area like Japan. In addition
      it has been generally accepted that the clinical onset of FMF begins before 20 yr
      of age in most patients. Onset of the disease at an older age may occur but is
      rare. Adult-onset FMF may be a form of disease with distinct clinical,
      demographic and molecular characteristics. We describe a case of adult-onset FMF
      confirmed by DNA analysis of the MEFV gene in a Korean patient. A 32-yr-old man,
      who has no family history of FMF, presented with periodic fever, abdominal pain
      and vomiting. Though several various tests were thoroughly performed to evaluate
      the cause of his symptoms, there was no evidence of infectious, autoimmune or
      neoplastic diseases. Several gene analysis of periodic fever syndrome was finally
      performed and two point mutations (p.Leu110Pro, p.Glu148Gln) were identified. We
      confirmed the first adult case of FMF through detection of MEFV gene mutations in
      Korea and describe his clinical characteristics.

PMID- 23166429
TI  - The return of an old worm: cerebral paragonimiasis presenting with intracerebral
      hemorrhage.
AB  - Paragonimiasis is caused by ingesting crustaceans, which are the intermediate
      hosts of Paragonimus. The involvement of the brain was a common presentation in
      Korea decades ago, but it becomes much less frequent in domestic medical
      practices. We observed a rare case of cerebral paragonimiasis manifesting with
      intracerebral hemorrhage. A 10-yr-old girl presented with sudden-onset
      dysarthria, right facial palsy and clumsiness of the right hand. Brain imaging
      showed acute intracerebral hemorrhage in the left frontal area. An occult
      vascular malformation or small arteriovenous malformation compressed by the
      hematoma was initially suspected. The lesion progressed for over 2 months until a
      delayed surgery was undertaken. Pathologic examination was consistent with
      cerebral paragonimiasis. After chemotherapy with praziquantel, the patient was
      monitored without neurological deficits or seizure attacks for 6 months. This
      case alerts practicing clinicians to the domestic transmission of a forgotten
      parasitic disease due to environmental changes.

PMID- 23166430
TI  - First case of Bartonella quintana endocarditis in Korea.
AB  - Since microbial gene sequencing was utilized for etiologic diagnosis of culture
      negative endocarditis, cases of Bartonella endocarditis have been reported in
      various countries. Herein we report the first case of Bartonella quintana
      endocarditis, which was confirmed for the first time in Korea by 16S rRNA gene
      sequencing from the excised valve. A 75-yr-old woman was hospitalized due to
      dyspnea. Echocardiography demonstrated large oscillating vegetation at the aortic
      valve. Blood culture was negative. She underwent valve replacement and sequencing
      of the 16S rRNA gene from excised valve identified Bartonella quintana. She was
      successfully treated with combined use of ceftriaxone and gentamicin.

PMID- 23166431
TI  - Membranous nephropathy in a 13-year-old boy with common variable
      immunodeficiency.
AB  - Various forms of hypogammaglobulinemia can occur in patients with autoimmune
      diseases and vice versa. We report a 13-yr-old boy with membranous nephropathy
      and common variable immunodeficiency. He presented with the nephrotic syndrome,
      pneumonia with bronchiectasis, and profound hypogammaglobulinemia. Renal biopsy
      showed diffusely thickened glomerular capillary walls with 'spikes' suggesting a
      membranous nephropathy. Secondary causes were ruled out by laboratory studies;
      however, heavy proteinuria persisted with steroid therapy. Cyclosporine and
      intravenous immunoglobulin were added, and the patient was discharged with
      decreased proteinuria. Hypogammaglobulinemia may have a deleterious impact on the
      immune dysregulation in some patients with membranous nephropathy.

PMID- 23166432
TI  - A case of congenital adrenal hyperplasia mimicking Cushing's syndrome.
AB  - Congenital adrenal hyperplasia (CAH) is characterized by decreased adrenal
      hormone production due to enzymatic defects and subsequent rise of
      adrenocorticotrophic hormone that stimulates the adrenal cortex to become
      hyperplastic, and sometimes tumorous. As the pathophysiology is basically a
      defect in the biosynthesis of cortisol, one may not consider CAH in patients with
      hypercortisolism. We report a case of a 41-yr-old man with a 4 cm-sized left
      adrenal tumorous lesion mimicking Cushing's syndrome who was diagnosed with CAH.
      He had central obesity and acanthosis nigricans involving the axillae together
      with elevated 24-hr urine cortisol level, supporting the diagnosis of Cushing's
      syndrome. However, the 24-hr urine cortisol was suppressed by 95% with the low
      dose dexamethasone suppression test. CAH was suspected based on the history of
      precocious puberty, short stature and a profound suppression of cortisol
      production by dexamethasone. CAH was confirmed by a remarkably increased level of
      serum 17-hydroxyprogesterone level. Gene mutation analysis revealed a compound
      heterozygote mutation of CYP21A2 (I173N and R357W).

PMID- 23166433
TI  - Phacomatosis pigmentokeratotica without extracutaneous abnormalities: a case
      study involving a preterm baby.
AB  - Phacomatosis pigmentokeratotica (PPK) is a rare syndrome defined by the
      association of an organoid nevus occasionally with sebaceous differentiation, a
      speckled lentiginous nevus, and other extracutaneous anomalies. A preterm male
      infant of only 830 g at 27 week gestational age had an organoid nevus showing
      sebaceous differentiation. Also, he had multiple speckled-lentiginous nevus.
      Correlating the observed clinical presentation with the histopathological
      findings, the diagnosis of PPK was established. There have been less than 10
      cases of PPK without extracutaneous manifestation. We present an uncommon case of
      a preterm patient with PPK who had no extracutaneous abnormalities.

PMID- 23166434
TI  - Visceral fat and liver fat as risk factors of metabolic syndrome.

PMID- 23166436
TI  - A novel preparation method for silicone oil nanoemulsions and its application for
      coating hair with silicone.
AB  - BACKGROUND: Silicone oil, as a major component in conditioner, is beneficial in
      the moisture preservation and lubrication of hair. However, it is difficult for
      silicone oil to directly absorb on the hair surface because of its
      hydrophobicity. Stable nanoemulsions containing silicone oil may present as a
      potential solution to this problem. METHODS: Silicone oil nanoemulsions were
      prepared using the oil-in-water method with nonionic surfactants. Emulsion
      particle size and distribution were characterized by scanning electron
      microscopy. The kinetic stability of this nanoemulsion system was investigated
      under accelerated stability tests and long-term storage. The effect of silicone
      oil deposition on hair was examined by analyzing the element of hair after
      treatment of silicone oil nanoemulsions. RESULTS: Nonionic surfactants such as
      Span 80 and Tween 80 are suitable emulsifiers to prepare oil-in-water
      nanoemulsions that are both thermodynamically stable and can enhance the
      absorption of silicone oil on hair surface. CONCLUSION: The silicone oil-in-water
      nanoemulsions containing nonionic surfactants present as a promising solution to
      improve the silicone oil deposition on the hair surface for hair care
      applications.

PMID- 23166437
TI  - Polyacrylonitrile nanofibers coated with silver nanoparticles using a modified
      coaxial electrospinning process.
AB  - BACKGROUND: The objective of this investigation was to develop a new class of
      antibacterial material in the form of nanofibers coated with silver nanoparticles
      (AgNPs) using a modified coaxial electrospinning approach. Through manipulation
      of the distribution on the surface of nanofibers, the antibacterial effect of Ag
      can be improved substantially. METHODS: Using polyacrylonitrile (PAN) as the
      filament-forming polymer matrix, an electrospinnable PAN solution was prepared as
      the core fluid. A silver nitrate (AgNO3) solution was exploited as sheath fluid
      to carry out the modified coaxial electrospinning process under varied sheath-to
      core flow rate ratios. RESULTS: Scanning electron microscopy and transmission
      electron microscopy demonstrated that the sheath AgNO3 solution can take a role
      in reducing the nanofibers' diameters significantly, a sheath-to-core flow rate
      ratio of 0.1 and 0.2 resulting in PAN nanofibers with diameters of 380 +/- 110 nm
      and 230 +/- 70 nm respectively. AgNPs are well distributed on the surface of PAN
      nanofibers. The antibacterial experiments demonstrated that these nanofibers show
      strong antimicrobial activities against Bacillus subtilis Wb800, and Escherichia
      coli dh5alpha. CONCLUSION: Coaxial electrospinning with AgNO3 solution as sheath
      fluid not only facilitates the electrospinning process, providing nanofibers with
      reduced diameters, but also allows functionalization of the nanofibers through
      coating with functional ingredients, effectively ensuring that the active
      antibacterial component is on the surface of the material, which leads to
      enhanced activity. We report an example of the systematic design, preparation,
      and application of a novel type of antibacterial material coated with AgNPs via a
      modified coaxial electrospinning methodology.

PMID- 23166438
TI  - Effect of particle size on solubility, dissolution rate, and oral
      bioavailability: evaluation using coenzyme Q10 as naked nanocrystals.
AB  - In this paper work, four naked nanocrystals (size range 80-700 nm) were prepared
      without any surfactant or polymer using the solvent/nonsolvent method. The
      effects of particle size on their solubility, dissolution, and oral
      bioavailability were investigated. Solubility and dissolution testing were
      performed in three types of dissolution medium, and the studies demonstrated that
      the equilibrium solubilities of coenzyme Q10 nanocrystals and bulk drugs were not
      affected by the dissolution media but the kinetic solubilities were. Kinetic
      solubility curves and changes in particle size distribution were determined and
      well explained by the proposed solubilization model for the nanocrystals and bulk
      drugs. The particle size effect on dissolution was clearly influenced by the
      diffusion coefficients of the various dissolution media, and the dissolution
      velocity of coenzyme Q10 increased as particle size decreased. The
      bioavailability of coenzyme Q10 after oral administration in beagle dogs was
      improved by reducing the particle size. For 700 nm nanocrystals, the AUC0-48 was
      4.4-fold greater than that for the coarse suspensions, but a further decrease in
      particle size from 700 nm to 120 nm did not contribute to improvement in
      bioavailability until the particle size was reduced to 80 nm, when
      bioavailability was increased by 7.3-fold.

PMID- 23166439
TI  - Preparation of Fe3O4 magnetic nanoparticles coated with gallic acid for drug
      delivery.
AB  - BACKGROUND AND METHODS: Magnetic iron oxide nanoparticles were prepared using a
      sonochemical method under atmospheric conditions at a Fe2+ to Fe3+ molar ratio of
      1:2. The iron oxide nanoparticles were subsequently coated with chitosan and
      gallic acid to produce a core-shell structure. RESULTS: X-ray diffraction
      demonstrated that the magnetic nanoparticles were pure Fe3O4 with a cubic inverse
      spinel structure. Transmission electron microscopy showed that the Fe3O4
      nanoparticles were of spherical shape with a mean diameter of 11 nm, compared
      with 13 nm for the iron oxide-chitosan-gallic acid (FCG) nanocarriers.
      CONCLUSION: The magnetic nanocarrier enhanced the thermal stability of the drug,
      gallic acid. Release of the active drug from the FCG nanocarrier was found to
      occur in a controlled manner. The gallic acid and FCG nanoparticles were not
      toxic in a normal human fibroblast (3T3) line, and anticancer activity was higher
      in HT29 than MCF7 cell lines.

PMID- 23166440
TI  - The amorphous solid dispersion of the poorly soluble ABT-102 forms
      nano/microparticulate structures in aqueous medium: impact on solubility.
AB  - Amorphous solid dispersions (ASDs) are a promising formulation approach for
      poorly soluble active pharmaceutical ingredients (APIs), because they ideally
      enhance both dissolution rate and solubility. However, the mechanism behind this
      is not understood in detail. In the present study, we investigated the
      supramolecular and the nano/microparticulate structures that emerge spontaneously
      upon dispersion of an ASD in aqueous medium and elucidated their influence on
      solubility. The ASD, prepared by hot melt extrusion, contained the poorly soluble
      ABT-102 (solubility in buffer, 0.05 MUg/mL), a hydrophilic polymer, and three
      surfactants. The apparent solubility of ABT-102 from the ASD-formulation was
      enhanced up to 200 times in comparison to crystalline ABT-102. At the same time,
      the molecular solubility, as assessed by inverse equilibrium dialysis, was
      enhanced two times. Asymmetrical flow field-flow fractionation in combination
      with a multiangle light-scattering detector, an ultraviolet detector, and a
      refractometer enabled us to separate and identify the various supramolecular
      assemblies that were present in the aqueous dispersions of the API-free ASD
      (placebo) and of binary/ternary blends of the ingredients. Thus, the
      supramolecular assemblies with a molar mass between 20,000 and 90,000 could be
      assigned to the polyvinylpyrrolidone/vinyl acetate 64, while two other kinds of
      assemblies were assigned to different surfactant assemblies (micelles). The
      amount of ABT-102 remaining associated with each of the assemblies upon
      fractionation was quantified offline with high-performance liquid chromatography
      ultraviolet-visible. The polymeric and the micellar fraction contributed to the
      substantial increase in apparent solubility of ABT-102. Furthermore, a
      microparticulate fraction was isolated by centrifugation and analyzed by scanning
      electron microscopy, X-ray scattering, and infrared spectroscopy. The
      microparticles were found to be amorphous and to contain two of the surfactants
      besides ABT-102 as the main component. The amorphous microparticles are assumed
      to be the origin of the observed increase in molecular solubility ("true"
      supersaturation).

PMID- 23166441
TI  - Treatment with exenatide once weekly or twice daily for 30 weeks is associated
      with changes in several cardiovascular risk markers.
AB  - BACKGROUND: Cyslipidemia and type 2 diabetes are two of the most significant risk
      factors for the development of cardiovascular disease. Measurement of lipoprotein
      subclasses provides important information about derangements in lipid metabolism
      and helps refine cardiovascular risk assessment. Exenatide, a glucagon-like
      peptide 1 receptor agonist, improved glycemic control, obesity, hypertension, and
      dyslipidemia in patients with type 2 diabetes in clinical trials. METHODS: In the
      DURATION-1 trial, patients with type 2 diabetes were treated with exenatide once
      weekly or twice daily for 30 weeks. This post hoc analysis evaluated the impact
      of exenatide on lipoprotein subclasses in 211 DURATION-1 patients using vertical
      auto profile methodology and the Statistical Package for the Social Sciences
      general linear model adjusted for glycosylated hemoglobin (HbA(1c)) and weight.
      RESULTS: Baseline lipids and high sensitivity C-reactive protein were normal
      overall based on the standard lipid panel. Once-weekly exenatide reduced
      apolipoprotein B and the apolipoprotein B to apolipoprotein A1 ratio (P < 0.05),
      independent of glycemic improvement and weight loss. A significant shift in
      lipoprotein pattern away from small, dense low-density lipoprotein-4 cholesterol
      was also observed (P < 0.05). Exenatide once weekly increased high-density
      lipoprotein-2 cholesterol, even after adjustment for changes in HbA(1c) and
      weight (P < 0.05). Triglycerides, very low-density lipoprotein cholesterol, and
      high sensitivity C-reactive protein were reduced with both the once-weekly and
      twice-daily exenatide regimens (P < 0.05). CONCLUSION: In this post hoc analysis,
      exenatide significantly improved a number of cardiovascular risk markers.
      Continuous exenatide exposure with exenatide once weekly elicited a greater
      response than did immediate-release exenatide twice daily, generally independent
      of glycemic improvement and weight loss. Thus, in addition to improving glycemic
      control, exenatide induced favorable changes in lipid and lipoprotein metabolism
      and decreased systemic inflammation.

PMID- 23166442
TI  - Tumor necrosis factor signaling is implicated in intestinal mucosal injury of
      cancer cachexic mice.
AB  - This study will examine the relationship between tumor necrosis factor (TNF) and
      intestinal mucosal injury in a cancer cachexia mouse model. The C26
      adenocarcinoma cancer model was set up, and immunohistochemistry was performed to
      investigate the histological chances of injuring the intestinal mucosa and the
      intestinal villi. The liquid-phase protein chip was employed to examine the
      changes in TNF and its receptors. The results demonstrated an intestinal mucosal
      injury in the cancer cachexia mouse model. The height of the intestinal villi
      decreased, and thinner basal membrane thickness was noted. The serum TNF-alpha
      and sTNFR1 increased, while in the mucosa, the TNF-alpha concentration increased;
      sTNFR1 and sTNFR2 decreased when compared to the control group. In conclusion,
      there is a potential association between the TNF signaling pathway and the
      intestinal mucosal injury in a cancer cachexia mouse model. Such understanding
      provides insights into the development of novel therapeutic targets for
      intestinal mucosa protection in clinical practice.

PMID- 23166443
TI  - Budget impact analysis of two immunotherapy products for treatment of grass
      pollen-induced allergic rhinoconjunctivitis.
AB  - BACKGROUND: Grass pollen-induced allergic rhinoconjunctivitis constitutes a large
      burden for society. Up to 20% of European and United States (US) populations
      suffer from respiratory allergies, including grass pollen-induced allergic
      rhinoconjunctivitis. The majority of patients are treated with symptomatic
      medications; however, a large proportion remains uncontrolled despite use of such
      treatments. Specific immunotherapy is the only treatment documented to target the
      underlying cause of the disease, leading to a sustained effect after completion
      of treatment. The aim of this study was to compare the economic consequences of
      treating patients suffering from allergic rhinoconjunctivitis with either a grass
      allergy immunotherapy tablet (AIT) or subcutaneous immunotherapy (SCIT). METHODS:
      A budget impact analysis was applied comparing SQ-standardized grass AIT
      (Grazax((r)); Phleum pratense, 75,000 SQ-T/2,800 BAU; ALK, Denmark) with SCIT
      (Alutard((r)); P. pratense, 100,000 SQ-U/mL; ALK, Denmark). Budget impact
      analysis included health care utilization measured in physical units based on
      systematic literature reviews, guidelines, and expert opinions, as well as
      valuation in unit costs based on drug tariffs, physician fees, and wage
      statistics. Budget impact analysis was conducted from a Danish health care
      perspective. RESULTS: Treating patients suffering from allergic
      rhinoconjunctivitis with grass AIT instead of grass SCIT resulted in a total
      reduction in treatment costs of ?1291 per patient during a treatment course. This
      cost saving implies that approximately 40% more patients could be treated with
      grass AIT per year without influencing the cost of treatment. CONCLUSION: Budget
      impact analysis showed that grass AIT is a cost-saving alternative to SCIT when
      treating patients with grass pollen-induced allergic rhinoconjunctivitis.

PMID- 23166444
TI  - Skin permeability and pharmacokinetics of diclofenac epolamine administered by
      dermal patch in Yorkshire-Landrace pigs.
AB  - PURPOSE: This study compared the pharmacokinetic profile, and systemic and local
      absorption of diclofenac, following dermal patch application and oral
      administration in Yorkshire-Landrace pigs. PATIENTS AND METHODS: Twelve
      anesthetized, female, Yorkshire-Landrace pigs were randomized to receive either
      the dermal patch (FLECTOR((r)) patch, 10 * 14 cm; Alpharma Pharmaceuticals, a
      subsidiary of Pfizer Inc, New York, NY) or 50 mg oral diclofenac (Voltaren((r));
      Novartis, East Hanover, NJ). Tissue (skin area of 2 * 2 cm and underlying muscles
      approximately 2-3 cm in depth) and blood (10 mL) samples were collected at timed
      intervals up to 11.5 hours after initial patch application or oral
      administration. The concentrations of diclofenac in plasma, skin, and muscle
      samples were analyzed using validated ultra performance liquid chromatography
      tandem mass spectrometric methods. RESULTS: Peak systemic exposure of diclofenac
      was very low by dermal application compared with oral administration (maximum
      concentration [C(max)] values of 3.5 vs 9640 ng/mL, respectively). Absorption of
      diclofenac into underlying muscles beneath the dermal patch was sustained, and
      followed apparently zero-order kinetics, with the skin serving as a depot with
      elevated concentrations of diclofenac. Concentrations of diclofenac in muscles
      beneath the patch application site were similar to corresponding tissues after
      oral administration (C(max) values of 879 and 1160 ng/mL, respectively). In
      contrast to the wide tissue distribution of diclofenac after oral administration,
      dermal patch application resulted in high concentrations of diclofenac only on
      the treated skin and immediate tissue underneath the patch. Low concentrations of
      diclofenac were observed in the skin and muscles collected from untreated areas
      contralateral to the site of dermal patch application. CONCLUSION: Dermal patch
      application resulted in low systemic absorption and high tissue penetration of
      diclofenac compared with oral administration.

PMID- 23166445
TI  - A large animal neuropathic pain model in sheep: a strategy for improving the
      predictability of preclinical models for therapeutic development.
AB  - BACKGROUND: Evaluation of analgesics in large animals is a necessary step in the
      development of better pain medications or gene therapy prior to clinical trials.
      However, chronic neuropathic pain models in large animals are limited. To address
      this deficiency, we developed a neuropathic pain model in sheep, which shares
      many anatomical similarities in spine dimensions and cerebrospinal fluid volume
      as humans. METHODS: A neuropathic pain state was induced in sheep by tight
      ligation and axotomy of the common peroneal nerve. The analgesic effect of
      intrathecal (IT) morphine was investigated. Interspecies comparison was conducted
      by analyzing the ceiling doses of IT morphine for humans, sheep, and rats.
      RESULTS: Peroneal nerve injury (PNI) produced an 86% decrease in von-Frey
      filament-evoked withdrawal threshold on postsurgery day 3 and the decrease lasted
      for the 8-week test period. Compared to the pre-injury, sham, and contralateral
      hindlimb, the IT morphine dose that produces 50% of maximum analgesia (ED(50))
      for injured PNI hindlimb was 1.8-fold larger and E(max), the dose that produces
      maximal analgesia, was 6.1-fold lower. The sheep model closely predicts human IT
      morphine ceiling dose by allometric scaling. This is in contrast to the
      approximately 10-fold lower morphine ceiling dose predicted by the rat spinal
      nerve ligated or spared nerve injury models. CONCLUSION: PNI sheep model has a
      fast onset and shows stable and long-lasting pain behavioral characteristics.
      Since the antinociceptive properties of IT morphine are similar to those observed
      in humans, the PNI sheep model will be a useful tool for the development of
      analgesics. Its large size and consistent chronic pain behavior will facilitate
      the development and evaluation of surgical intervention and gene therapy. The PNI
      sheep pain model provides us with the opportunity for multi-species testing,
      which will improve the success of clinical trials.

PMID- 23166446
TI  - Lifestyle-oriented non-pharmacological treatments for fibromyalgia: a clinical
      overview and applications with home-based technologies.
AB  - Fibromyalgia (FM) is a persistent and disabling widespread pain condition often
      accompanied by chronic fatigue, cognitive problems, sleep disturbance,
      depression, anxiety, and headache. To date, the most thoroughly studied non
      pharmacological approaches to managing FM are those with a focus on changing
      patient activities and beliefs that affect the illness. These interventions are
      intended to facilitate enduring improvement in pain and functional status.
      Lifestyle-oriented treatments include patient education, aerobic or other
      physical exercise, and cognitive-behavioral therapy (CBT). These interventions in
      FM can be delivered in medical or behavioral health care settings by trained
      professionals, through patient-oriented treatment manuals, or via remote-access
      technologies. Non-pharmacological treatments, in particular exercise and CBT,
      have yielded effect sizes and cost-benefit ratios comparable to medications. This
      paper describes lifestyle-oriented non-pharmacological treatments for FM and
      highlights selected literature reviews of these interventions. In addition,
      behavioral and practical issues are addressed that may affect these non
      pharmacological treatments, including patient expectations, participant burden,
      and treatment availability. Recommendations are made to facilitate these
      interventions and potentially improve outcomes. In particular, the increasing
      availability of convenient home-based mobile technologies to deliver these non
      pharmacological treatments is described.

PMID- 23166447
TI  - Therapeutic utility of palmitoylethanolamide in the treatment of neuropathic pain
      associated with various pathological conditions: a case series.
AB  - Palmitoylethanolamide (PEA), an endogenous fatty acid amide, has been
      demonstrated to bind to a receptor in the cell nucleus - the peroxisome
      proliferator-activated receptor - and performs a great variety of biological
      functions related to chronic and neuropathic pain and inflammation, as has been
      demonstrated in clinical trials. These include peripheral neuropathies such as
      diabetic neuropathy, chemotherapy-induced peripheral neuropathy, carpal tunnel
      syndrome, sciatic pain, osteoarthritis, low-back pain, failed back surgery
      syndrome, dental pains, neuropathic pain in stroke and multiple sclerosis,
      chronic pelvic pain, postherpetic neuralgia, and vaginal pains. Probably due to
      the fact that PEA is an endogenous modulator as well as a compound in food, such
      as eggs and milk, no serious side effects have been reported, nor have drug-drug
      interactions. This article presents a case series describing the application and
      potential efficacy and safety of PEA in the treatment of various syndromes
      associated with chronic pain that is poorly responsive to standard therapies.

PMID- 23166448
TI  - Neuroplastic alteration of TTX-resistant sodium channel with visceral pain and
      morphine-induced hyperalgesia.
AB  - The discovery of the tetrodotoxin-resistant (TTX-R) Na(+) channel in nociceptive
      neurons has provided a special target for analgesic intervention. In a previous
      study we found that both morphine tolerance and persistent visceral inflammation
      resulted in visceral hyperalgesia. It has also been suggested that
      hyperexcitability of sensory neurons due to altered TTX-R Na(+) channel
      properties and expression contributes to hyperalgesia; however, we do not know if
      some TTX-R Na(+) channel property changes can be triggered by visceral
      hyperalgesia and morphine tolerance, or whether there are similar molecular or
      channel mechanisms in both situations. To evaluate the effects of morphine
      tolerance and visceral inflammation on the channel, we investigated the dorsal
      root ganglia (DRG) neuronal change following these chronic treatments. Using
      whole-cell patch clamp recording, we recorded TTX-R Na(+) currents in isolated
      adult rat lumbar and sacral (L6-S2) DRG neurons from normal and pathologic rats
      with colon inflammatory pain or chronic morphine treatment. We found that the
      amplitudes of TTX-R Na(+) currents were significantly increased in small-diameter
      DRG neurons with either morphine tolerance or visceral inflammatory pain.
      Meanwhile, the result also showed that those treatments altered the kinetics
      properties of the electrical current (ie, the activating and inactivating speed
      of the channel was accelerated). Our current results suggested that in both
      models, visceral chronic inflammatory pain and morphine tolerance causes
      electrophysiological changes in voltage-gated Na channels due to the chronic
      administration of these medications. For the first time, the present
      investigation explored the adaptations of this channel, which may contribute to
      the hyperexcitability of primary afferent nerves and hyperalgesia during these
      pathologic conditions. The results also suggest that neurophysiologic mechanisms
      of morphine tolerance and visceral hyperalgesia are related at the TTX-R Na(+)
      channel.

PMID- 23166449
TI  - Subgroups based on thermal and pressure pain thresholds in women with chronic
      whiplash display differences in clinical presentation - an explorative study.
AB  - PURPOSE: To investigate the presence of subgroups in chronic whiplash-associated
      disorders (WAD) based on pain thresholds for pressure (PPT), cold (CPT), and heat
      (HPT) and to compare these subgroups with respect to symptomatology, disability,
      and health aspects. METHODS: Two groups of female subjects - patients with
      chronic WAD (n = 28) and healthy controls (CON; n = 29) - were investigated.
      Quantitative sensory testing (QST) for thermal thresholds and algometry for PPT
      at four sites in the body (over the trapezius and tibialis anterior bilaterally)
      were determined. Habitual pain intensities, psychological strain, disability, and
      health aspects were registered using a questionnaire. RESULTS: A CLUSTER ANALYSIS
      BASED ON PPT, CPT, AND HPT IDENTIFIED TWO SUBGROUPS OF CHRONIC WAD: one sensitive
      subgroup (s-WAD; n = 21), and one less sensitive subgroup (ls-WAD; n = 6). S-WAD
      displayed widespread hyperalgesia, whereas ls-WAD had localized hyperalgesia in
      the neck area, with tendencies to supernormal values in remote areas of the body.
      Generally, s-WAD had a significantly worse situation than the CON with respect to
      symptomatology, disability, and health aspects. The ls-WAD group was intermediary
      between s-WAD and CON in these aspects. CONCLUSION: Different explanations, eg,
      severity of the pain condition per se, etiological factors, and pre-trauma
      differences in pain sensitivity, may exist for the differences in pain thresholds
      between the two subgroups. Future research should investigate the role of pain
      thresholds in the chronic stage to determine the efficacy of treatment
      interventions.

PMID- 23166450
TI  - Repeat-dose steady-state pharmacokinetic evaluation of once-daily hydromorphone
      extended-release (OROS((r)) hydromorphone ER) in patients with chronic pain.
AB  - OBJECTIVE: To characterize the steady-state pharmacokinetic profile of
      hydromorphone extended-release (ER) in patients with chronic pain taking
      concomitant medications. METHODS: This open-label repeat-dose study enrolled 22
      patients (mean age, 51.4 years; 81.8% female). All patients were receiving at
      least one concomitant medication; 86.4% were receiving at least two concomitant
      medications and 81.8% were receiving at least three. Patients receiving a stable
      dose of an opioid were converted to hydromorphone ER at a 5:1 ratio (morphine
      equivalent:hydromorphone). The dose was titrated to adequate analgesia over 3-14
      days and stabilized between 8-48 mg. Oral morphine immediate-release was
      permitted for breakthrough pain. Area under the concentration-time curve from 0
      24 hours (AUC(0-24)), maximum plasma concentration (C(max)), trough plasma
      concentration (C(min)), average plasma concentration (C(avg)), and degree of
      fluctuation (100 * [(C(max) - C(min)) / C(avg)]) were calculated based on data
      from 14 patients. RESULTS: Dose-normalized to 16 mg, mean pharmacokinetic
      parameter values were: AUC(0-24), 41.1 ng . h/mL; C(max), 2.6 ng/mL; C(min), 1.1
      ng/mL; C(avg), 1.7 ng/mL; and the degree of fluctuation was 99.6%. The
      pharmacokinetic profile of hydromorphone ER was linear and consistent with dose
      proportionality. Mean pain intensity difference scores showed statistically
      significant improvement from 2-21 hours after dosing. Sixteen (72.7%) patients
      reported at least one adverse event (AE). The most common were constipation
      (31.8%), headache (22.7%), and vomiting (13.6%). One patient discontinued
      treatment due to vomiting. No deaths, serious AEs, or unexpected AEs occurred.
      CONCLUSION: These findings replicate and extend the steady-state pharmacokinetic
      profile of hydromorphone ER, previously characterized in healthy volunteers, to a
      population of chronic pain patients taking numerous concomitant medications.

PMID- 23166451
TI  - Crucial involvement of actin filaments in celecoxib and morphine analgesia in a
      model of inflammatory pain.
AB  - BACKGROUND: Celecoxib exerted analgesic effects (hypoalgesia) reversed by opioid
      receptor antagonists in a model of inflammatory pain. To analyze this celecoxib
      induced hypoalgesia further, we assessed the effects of several disruptors of
      cytoskeletal components in our model of inflammation. METHODS: Hyperalgesia to
      mechanical stimuli was induced in rat hind paws by intraplantar injection of
      carrageenan and measured using the Randall-Selitto method over the next 8 hours.
      The effects of systemic pretreatment with celecoxib and a range of cytoskeletal
      disruptors (colchicine, nocodazole, cytochalasin B, latrunculin B, acrylamide,
      each given by intraplantar injection) on carrageenan-induced hyperalgesia were
      similarly investigated. Morphine and other selective cyclo-oxygenase 1 (SC-560),
      cyclo-oxygenase 2 (SC-236), and nonselective cyclo-oxygenase (indomethacin)
      inhibitors were also tested under similar conditions. RESULTS: None of the
      cytoskeletal disruptors affected the peak intensity of carrageenan-induced
      hyperalgesia, and its duration was increased only by nocodazole and colchicine.
      Pretreatment with celecoxib 30 minutes before carrageenan reversed the
      hyperalgesia and raised the nociceptive threshold (hypoalgesia). All analgesic
      effects of celecoxib were blocked by nocodazole, colchicine, cytochalasin B, and
      latrunculin B. Pretreatment with morphine also induced hypoalgesia in carrageenan
      inflamed paws, an effect reversed by colchicine and cytochalasin B. However, the
      analgesic effects of indomethacin were not reversed by disruption of actin
      filaments with cytochalasin B or latrunculin B. CONCLUSION: These data strengthen
      the correlation between cytoskeletal structures and the processes of pain and
      analgesia.

PMID- 23166452
TI  - Evaluation of a novel, ultrathin, tip-bending endoscope in a synthetic force
      sensing pancreas with comparison to medical guide wires.
AB  - PURPOSE: Direct visualization of pancreatic ductal tissue is critical for early
      diagnosis of pancreatic diseases and for guiding therapeutic interventions. A
      novel, ultrathin (5 Fr) scanning fiber endoscope (SFE) with tip-bending
      capability has been developed specifically to achieve high resolution imaging as
      a pancreatoscope during endoscopic retrograde cholangiopancreatography (ERCP).
      This device has potential to dramatically improve both diagnostic and therapeutic
      capabilities during ERCP by providing direct video feedback and tool guidance to
      clinicians. METHODS: Invasiveness of the new tip-bending SFE was evaluated by a
      performance comparison to ERCP guide wires, which are routinely inserted into the
      pancreatic duct during ERCP. An in vitro test model with four force sensors
      embedded in a synthetic pancreas was designed to detect and compare the insertion
      forces for 0.89 mm and 0.53 mm diameter guide wires as well as the 1.7 mm
      diameter SFE. Insertions were performed through the working channel of a
      therapeutic duodenoscope for the two types of guide wires and using a
      statistically similar direct insertion method for comparison to the SFE. RESULTS:
      Analysis of the forces detected by the sensors showed the smaller diameter 0.53
      mm wire produced significantly less average and maximum forces during insertion
      than the larger diameter 0.89 mm wire. With the use of tip-bending and optical
      visualization, the 1.7 mm diameter SFE produced significantly less average force
      during insertion than the 0.89 mm wire at every sensor, despite its larger size.
      It was further shown that the use of tip-bending with the SFE significantly
      reduced the forces at all sensors, compared to insertions when tip-bending was
      not used. CONCLUSION: Combining high quality video imaging with two-axis tip
      bending allows a larger diameter guide wire-style device to be inserted into the
      pancreatic duct during ERCP with improved capacity to perform diagnostics and
      therapy.

PMID- 23166453
TI  - A magnetic resonance (MR) compatible selective brain temperature manipulation
      system for preclinical study.
AB  - There is overwhelming evidence that hypothermia can improve the outcome of an
      ischemic stroke. However, the most widely used systemic cooling method could lead
      to multiple side effects, while the incompatibility with magnetic resonance
      imaging of the present selective cooling methods highly limit their application
      in preclinical studies. In this study, we developed a magnetic resonance
      compatible selective brain temperature manipulation system for small animals,
      which can regulate brain temperature quickly and accurately for a desired period
      of time, while maintaining the normal body physiological conditions. This device
      was utilized to examine the relationship between T1 relaxation, cerebral blood
      flow, and temperature in brain tissue during magnetic resonance imaging of
      ischemic stroke. The results showed that this device can be an efficient brain
      temperature manipulation tool for preclinical studies needing local hypothermic
      or hyperthermic conditions.

PMID- 23166454
TI  - Electro interstitial scan system: assessment of 10 years of research and
      development.
AB  - BACKGROUND: Ten years of research and development have allowed an understanding
      of how the electro interstitial scan (EIS) works and what its clinical
      applications may be. MATERIALS AND METHODS: The EIS is a galvanic skin response
      device. The measurements are performed by electrical stimulation of the post
      sympathetic cholinergic fiber with weak DC current and voltage 1.28V applied
      during 2 minutes and in bipolar mode.  CURRENT SCIENTIFIC KNOWLEDGE: EIS
      ELECTRICAL MEASUREMENTS ARE RELATED TO: (1) the concentration of free chloride
      ions in the interstitial fluid, which affects the transfer of electrical current
      and the ratio intensity/voltage; (2) the morphology of the interstitial fluid,
      which is related to the electrical dispersion calculated from the Cole equation
      (alpha parameter); (3) electrical stimulation, which causes a change in sweat
      rate at the passive electrodes - post sympathetic cholinergic fiber electrical
      stimulation appears to be responsible for activating M2 receptors, which regulate
      nitric oxide (NO) production in the endothelial cell and cause vasodilation and a
      released sweat response; and (4) the electrochemical redox reactions
      (electrolysis) of the released sweat on electrodes, which are different on the
      bulk of the metal electrodes (O2 + [4H(+)] + [4e(-)]) and on the Ag/AgCl
      disposable electrodes (AgCl precipitation). RESULTS: FOR EACH OF THE EIS CLINICAL
      RESULTS, VARIOUS EXPLANATIONS WERE POSITED, SUCH AS: (1) electrical stimulation
      of the postsympathetic cholinergic fiber-activating NO production in the
      endothelial cell, which causes vasodilation and a released sweat response
      (diabetes detection); (2) estimation of interstitial fluid's acid-base balance,
      which is reflected in an electrochemical reaction on the bulk of the electrodes
      through the released sweat (prostate cancer detection); (3) estimation of
      cerebral interstitial fluid chloride ions (detection of ADHD in children); and
      (4) estimation of the morphology of the interstitial fluid (selective serotonin
      reuptake inhibitor treatment response). CONCLUSION: After 10 years of
      development, the analysis of current scientific knowledge and results of clinical
      investigations have allowed a better understanding of EIS electrical
      measurements.

PMID- 23166455
TI  - Flushing ports of totally implantable venous access devices, and impact of the
      Huber point needle bevel orientation: experimental tests and numerical
      computation.
AB  - The use of totally implantable venous access devices developed as a medical
      device allowing mid- and long-term, frequent, repeated, or continuous injection
      of therapeutic products, by vascular, cavitary, or perineural access. The
      effective flushing of these devices is a central element to assure long-lasting
      use. Our experimental work demonstrates that directing the Huber point needle
      opening in the diametrically opposite direction of the implantable port exit
      channel increases the flushing efficiency. These results are consolidated by
      numerical computations, which support recommendations not only for their
      maintenance, but also for their use.

PMID- 23166456
TI  - Decision-tree model for health economic comparison of two long-acting
      somatostatin receptor ligand devices in France, Germany, and the UK.
AB  - BACKGROUND: Long-acting somatostatin receptor ligands (SRL) with product-specific
      formulation and means of administration are injected periodically in patients
      with acromegaly and neuroendocrine tumors. A simple decision-tree model aimed at
      comparing cost savings with ready-to-use Somatuline Autogel((r)) (lanreotide) and
      Sandostatin LAR((r)) (octreotide) for the UK, France, and Germany. The drivers of
      cost savings studied were the reduction of time to administer as well as a
      reduced baseline risk of clogging during product administration reported for
      Somatuline Autogel((r)). METHODS: The decision-tree model assumed two settings
      for SRL administration, ie, by either hospital-based or community-based nurses.
      In the case of clogging, the first dose was assumed to be lost and a second
      injection performed. Successful injection depended on the probability of
      clogging. Direct medical costs were included. A set of scenarios were run,
      varying the cost drivers, such as the baseline risk of clogging, SRL
      administration time, and percentage of patients injected during a hospital stay.
      RESULTS: Costs per successful injection were less for Somatuline
      Autogel((r))/Depot, ranging from Euros (EUR) 13-45, EUR 52-108, and EUR 127-151,
      respectively, for France, Germany, and the UK. The prices for both long-acting
      SRL were the same in France, and cost savings came to 100% from differences other
      than drug prices. For Germany and the UK, the proportion of savings due to less
      clogging and shorter administration time was estimated to be around 32% and 20%,
      respectively. Based on low and high country-specific patient cohort size
      estimations of individuals eligible for SRL treatment among the patient
      population with acromegaly and neuroendocrine tumors, annual savings were
      estimated to be up to EUR 2,000,000 for France, EUR 6,000,000 for Germany, and
      EUR 7,000,000 for the UK. CONCLUSION: This model suggests that increasing usage
      of the Somatuline device for injection of SRL might lead to substantial savings
      for health care providers across Europe.

PMID- 23166457
TI  - Recent advances in noninvasive glucose monitoring.
AB  - The race for the next generation of painless and reliable glucose monitoring for
      diabetes mellitus is on. As technology advances, both diagnostic techniques and
      equipment improve. This review describes the main technologies currently being
      explored for noninvasive glucose monitoring. The principle of each technology is
      mentioned; its advantages and limitations are then discussed. The general
      description and the corresponding results for each device are illustrated, as
      well as the current status of the device and the manufacturer; internet
      references for the devices are listed where appropriate. Ten technologies and
      eleven potential devices are included in this review. Near infrared spectroscopy
      has become a promising technology, among others, for blood glucose monitoring.
      Although some reviews have been published already, the rapid development of
      technologies and information makes constant updating mandatory. While advances
      have been made, the reliability and the calibration of noninvasive instruments
      could still be improved, and more studies carried out under different
      physiological conditions of metabolism, bodily fluid circulation, and blood
      components are needed.

PMID- 23166458
TI  - A revision of Evaniscus  (Hymenoptera, Evaniidae) using ontology-based semantic
      phenotype annotation.
AB  - The Neotropical evaniid genus Evaniscus  Szepligeti currently includes six
      species. Two new species are described, Evaniscus lansdownei  Mullins, sp. n.
      from Colombia and Brazil and Evaniscus rafaeli  Kawada, sp. n. from Brazil.
      Evaniscus sulcigenis  Roman, syn. n., is synonymized under Evaniscus rufithorax 
      Enderlein. An identification key to species of Evaniscus  is provided. Thirty
      five parsimony informative morphological characters are analyzed for six ingroup
      and four outgroup taxa. A topology resulting in a monophyletic Evaniscus  is
      presented with Evaniscus tibialis  and Evaniscus rafaeli  as sister to the
      remaining Evaniscus  species. The Hymenoptera  Anatomy Ontology and other
      relevant biomedical ontologies are employed to create semantic phenotype
      statements in Entity-Quality (EQ) format for species descriptions. This approach
      is an early effort to formalize species descriptions and to make descriptive data
      available to other domains.

PMID- 23166459
TI  - A new marine gastrotrich from the State of Sao Paulo (Brazil), with a key to
      species of Pseudostomella (Gastrotricha, Thaumastodermatidae).
AB  - In previous papers, faunistic and preliminary taxonomic data on the gastrotrich
      communities along the coastline of the Brazilian states of Sao Paulo and Rio de
      Janeiro were reported; among the over 40 records, the occurrence of several
      species new to science was highlighted. One of such new taxa is described here
      based on observation carried out on living and SEM prepared specimens.
      Pseudostomella dolichopodasp. n. (Gastrotricha: Thaumastodermatidae) is the only
      species in the genus that attains 420 um in total length, is covered by
      pentancres and possesses, among others, caudal pedicles up to 45 um in length.
      Additional differences with co-generic taxa characterized by a pentancrous
      covering are discussed. Furthermore, a key to the described Pseudostomella
      species of the world based on easily discernible traits, visible in both living
      and formalin-fixed specimens, is provided.

PMID- 23166460
TI  - Doryctopambolus Nunes & Zaldivar-Riveron (Braconidae), a new neotropical
      doryctine wasp genus with propodeal spines.
AB  - The new Neotropical doryctine genus Doryctopambolusgen. n. is erected to contain
      Doryctopambolus pilcomayensis (van Achterberg & Braet, 2004), comb. n., which was
      previously placed within Pambolus (Pambolinae), as well as three new species,
      Doryctopambolus clebschisp. n., Doryctopambolus dominicanussp. n. and
      Doryctopambolus sarochensissp. n. Members of this new genus are mainly
      characterised by the presence of at least one pair of conspicuous propodeal apico
      lateral projections, which are similar to those present in all members of
      Pambolinae and in species of three Australasian doryctine genera. We generated
      DNA barcoding sequences for the three newly described species. We discuss the
      morphological similarity between species of the Australasian Echinodoryctes
      Belokobylskij, Iqbal & Austin and Doryctopambolus. A key for the described
      species of Doryctopambolus is provided.

PMID- 23166461
TI  - A revision of the genus Planinasus Cresson (Diptera, Periscelididae).
AB  - The genus Planinasus Cresson is revised and includes 18 extant and one fossil
      species. We clarify the status of the three previously described species and
      describe 15 new species as follows (type locality in parenthesis): Planinasus
      aenigmaticus (Colombia. Bogota: Bogota (04 degrees 35.8'N, 74 degrees 08.8'W)),
      Planinasus neotropicus (Panama. Canal Zone: Barro Colorado Island (09 degrees
      09.1'N, 79 degrees 50.8'W)), Planinasus kotrbae (Ecuador. Orellana: Rio Tiputini
      Biodiversity Station (0 degrees 38.2'S, 76 degrees 08.9'W)), Planinasus miradorus
      (Brazil. Maranhao: Parque Estadual Mirador, Base da Geraldina (06 degrees 22.2'S,
      44 degrees 21.8'W)), Planinasus tobagoensis (Trinidad and Tobago. Tobago. St.
      John: Parlatuvier (11 degrees 17.9'N, 60 degrees 39'W)), Planinasus xanthops
      (Ecuador. Orellana: Rio Tiputini Biodiversity Station (0 degrees 38.2'S, 76
      degrees 8.9'W)), Planinasus argentifacies (Peru. Madre de Dios: Rio Manu, Pakitza
      (11 degrees 56.6'S, 71 degrees 16.9'W; 250 m)), Planinasus insulanus (Dominican
      Republic. La Vega: near Jarabacoa, Salto Guasara (19 degrees 04.4'N, 70 degrees
      42.1'W, 680 m)), Planinasus nigritarsus (Guyana. Conservation of Ecological
      Interactions and Biotic Associations (CEIBA; ca. 40 km S Georgetown; 06 degrees
      29.9'N, 58 degrees 13.1'W)), Planinasus atriclypeus (Brazil. Rio de Janeiro: Rio
      de Janeiro, Floresta da Tijuca (22 degrees 57.6'S, 43 degrees 16.4'W)),
      Planinasus atrifrons (Bolivia. Santa Cruz: Ichilo, Buena Vista (4-6 km SSE; Hotel
      Flora y Fauna; 17 degrees 29.95'S, 63 degrees 33.15'W; 4-500 m)), P. flavicoxalis
      (West Indies. Dominica. St. David: 1.6 km N of junction of roads to Rosalie and
      Castle Bruce (15 degrees 23.8'N, 61 degrees 18.6'W)), Planinasus mcalpineorum
      (Mexico. Chiapas: Cacahoatan (7 km N; 15 degrees 04.1'N, 92 degrees 07.4'W)),
      Planinasus nigrifacies (Brazil. Sao Paulo: Mogi das Cruzes, Serra do Itapeti (23
      degrees 31.5'S, 46 degrees 11.2'W)), Planinasus obscuripennis (Peru. Madre de
      Dios: Rio Manu, Erika (near Salvacion; 12 degrees 50.7'S, 71 degrees 23.3'W; 550
      m)). In addition to external characters, we also describe and illustrate
      structures of the male terminalia and for Planinasus kotrbaesp. n., the internal
      female reproductive organs. Detailed locality data and distribution maps for all
      species are provided. For perspective and to facilitate genus-group and species
      group recognition, the family Periscelididae and subfamily Stenomicrinae are
      diagnosed and for the latter, a key to included genera is provided.

PMID- 23166462
TI  - Taxonomy, morphology, masticatory function and phylogeny of heterodontosaurid
      dinosaurs.
AB  - Heterodontosaurids comprise an important early radiation of small-bodied
      herbivores that persisted for approximately 100 My from Late Triassic to Early
      Cretaceous time. Review of available fossils unequivocally establishes Echinodon
      as a very small-bodied, late-surviving northern heterodontosaurid similar to the
      other northern genera Fruitadens and Tianyulong. Tianyulong from northern China
      has unusual skeletal proportions, including a relatively large skull, short
      forelimb, and long manual digit II. The southern African heterodontosaurid genus
      Lycorhinus is established as valid, and a new taxon from the same formation is
      named Pegomastax africanusgen. n., sp. n. Tooth replacement and tooth-to-tooth
      wear is more common than previously thought among heterodontosaurids, and in
      Heterodontosaurus the angle of tooth-to-tooth shear is shown to increase markedly
      during maturation. Long-axis rotation of the lower jaw during occlusion is
      identified here as the most likely functional mechanism underlying marked tooth
      wear in mature specimens of Heterodontosaurus. Extensive tooth wear and other
      evidence suggests that all heterodontosaurids were predominantly or exclusively
      herbivores. Basal genera such as Echinodon, Fruitadens and Tianyulong with
      primitive, subtriangular crowns currently are known only from northern
      landmasses. All other genera except the enigmatic Pisanosaurus have deeper crown
      proportions and currently are known only from southern landmasses.

PMID- 23166463
TI  - An illustrated key to the genera and subgenera of the Recent azooxanthellate
      Scleractinia (Cnidaria, Anthozoa), with an attached glossary.
AB  - The 120 presently recognized genera and seven subgenera of the azooxanthellate
      Scleractinia are keyed using gross morphological characters of the corallum. All
      genera are illustrated with calicular and side views of coralla. All termes used
      in the key are defined in an illustrated glossary. A table of all species-level
      keys, both comprehensive and faunistic, is provided covering the last 40 years.

PMID- 23166464
TI  - Profundulus kreiseri, a new species of Profundulidae (Teleostei,
      Cyprinodontiformes) from northwestern Honduras.
AB  - A new species of Profundulus, Profundulus kreiseri (Cyprinodontiformes:
      Profundulidae), is described from the Chamelecon and Ulua Rivers in the
      northwestern Honduran highlands. Based on a phylogenetic analysis using
      cytochrome b and the presence of synapomorphic characters (dark humeral spot, a
      scaled preorbital region and between 32-34 vertebrae), this new species is placed
      in the subgenus Profundulus, which also includes Profundulus (Profundulus)
      oaxacae, Profundulus (Profundulus) punctatus and Profundulus (Profundulus)
      guatemalensis. Profundulus kreiseri can be distinguished from other members of
      the subgenus Profundulus by having less than half of its caudal fin densely
      scaled. Profundulus kreiseri can further be differentiated from Profundulus
      (Profundulus) oaxacae and Profundulus (Profundulus) punctatus by the absence of
      rows of dark spots on its flanks. The new species can further be differentiated
      from Profundulus (Profundulus) guatemalensis by the presence of fewer caudal- and
      pectoral-fin rays. The new species is distinguished from congeners of the
      profundulid subgenus Tlaloc (viz., Profundulus (Tlaloc) hildebrandi, Profundulus
      (Tlaloc) labialis, Profundulus (Tlaloc) candalarius and Profundulus (Tlaloc)
      portillorum) by having a scaled preorbital region and a dark humeral spot.
      Profundulus kreiseri and Profundulus portillorum are the only two species of
      Profundulus that are endemic to the region south of the Motagua River drainage in
      southern Guatemala and northwestern Honduras.

PMID- 23166465
TI  - New Mecyclothorax spp. (Coleoptera, Carabidae, Moriomorphini) define Mont Mauru,
      eastern Tahiti Nui, as a distinct area of endemism.
AB  - Seven species of Mecyclothorax Sharp precinctive to Mont Mauru, Tahiti, Society
      Islands are newly described: Mecyclothorax tuteisp. n., Mecyclothorax tihotiisp.
      n., Mecyclothorax putaputasp. n., Mecyclothorax toretoresp. n., Mecyclothorax
      anaanasp. n., Mecyclothorax pirihaosp. n., and Mecyclothorax porosp. n. These
      seven constitute the first representative Mecyclothorax species recorded from
      Mauru, and their geographic restriction to this isolated massif defines it as a
      distinct area of endemism along the highly dissected eastern versant of the
      Tahiti Nui volcano. Each of the new species has a closest relative on another
      massif of Tahiti Nui, supporting speciation associated with vicariance caused by
      extensive erosional valley formation, especially the development of Papenoo
      Valley. Comparison of the known elevational distributions of the new discoveries
      on Mont Mauru to the elevational diversity profile of the comparatively well
      sampled Mont Marau, northwest Tahiti Nui, suggests that numerous Mecyclothorax
      species remain to be discovered in higher-elevation habitats of Mont Mauru.

PMID- 23166466
TI  - Corrigenda: Sereno PC (2012) Taxonomy, morphology, masticatory function and
      phylogeny of heterodontosaurid dinosaurs. ZooKeys 226: 1-225.

PMID- 23166467
TI  - Review of the genus Tinissa Walker, 1864 (Lepidoptera, Tineidae, Scardiinae) from
      China, with description of five new species.
AB  - The genus Tinissa Walker is reviewed for China. Seven species are recognized, of
      which Tinissa apicimaculatasp. n., Tinissa conchatasp. n., Tinissa connatasp.
      n.,Tinissa leguminellasp. n. and Tinissa spirellasp. n. are described as new; and
      Tinissa insularia Robinson, 1976 is newly recorded from China. Photographs of the
      adults and illustrations of the genitalia are given. A key to all the known
      Chinese species and a distribution map of Tinissa in China are included.

PMID- 23166468
TI  - Forever in the dark: the cave-dwelling azooxanthellate reef coral Leptoseris
      troglodyta sp. n. (Scleractinia, Agariciidae).
AB  - The coral species Leptoseris troglodytasp. n. (Scleractinia, Agariciidae) is
      described as new to science. It is the first known azooxanthellate shallow-water
      agariciid and is recorded from the ceilings of caves at 5-35 m depth in West
      Pacific coral reefs. The corals have monocentric cup-shaped calices. They may
      become colonial through extramural budding from the basal coenosteum, which may
      cause adjacent calices to fuse. The size, shape and habitat of Leptoseris
      troglodyta are unique compared to other Leptoseris species, many of which have
      been recorded from mesophotic depths. The absence of zooxanthellae indicates that
      it may survive well in darkness, but endolithic algae in some corals indicate
      that they may be able to get some light. The presence of menianes on the septal
      sides, which may help to absorb light at greater depths in zooxanthellate corals,
      have no obvious adaptive relevance in the new species and could have been
      inherited from ancestral species that perhaps were zooxanthellate. The new
      species may be azooxanthellate as derived through the loss of zooxanthellae,
      which would be a reversal in Leptoseris phylogeny.

PMID- 23166469
TI  - First record of the ant subfamily Aenictinae (Hymenoptera, Formicidae) from Saudi
      Arabia, with the description of a new species.
AB  - The ant subfamily Aenictinae is recorded for the first time from the Kingdom of
      Saudi Arabia and for the second time from the Arabian Peninsula. A new species
      Aenictus arabicussp. n., is described from the worker caste. Aenictus arabicus
      belongs to the Aenictus wroughtonii-group and appears to be most closely related
      to Aenictus rhodiensis Menozzi, but can be easily distinguished from the latter
      by the following characters: overall smaller size; cephalic index (head
      width/head length) small; occipital corners in lateral view rounded; antennal
      scape when laid back surpassing approximately two-thirds of head length;
      funicular segments 2-8 each at least 2* as long as broad; subpetiolar process
      well developed; petiole and postpetiole distinctly imbricate; gaster and clypeus
      entirely yellow, teeth of mandibles reddish- brown. Aenictus arabicus was
      collected from leaf litter, next to a tree of Psidium guajava L. The new species
      also is similar to Aenictus sagei and Aenictus wroughtonii. Affinities and a key
      to related species of the species group are given.

PMID- 23166470
TI  - A new genus of the tribe Issini (Hemiptera, Fulgoromorpha, Issidae) from China.
AB  - Macrodarumoides petalinus, a new genus and species of Issidae (Hemiptera) are
      described based on specimens from Yunnan and Guangxi, China.

PMID- 23166471
TI  - A review of the genus Megapulvinaria Young (Hemiptera, Coccoidea, Coccidae) from
      China, with a description of a new species.
AB  - Prior to this study, only Megapulvinaria maxima (Green) was known from China.
      However, a new species Megapulvinaria beihaiensis Wang & Feng, sp. n. is
      described below and Megapulvinaria maxima is redescribed. A key is provided for
      the five species now placed in this genus.

PMID- 23166472
TI  - Dental morphology of the Lesser Bamboo Rat, Cannomys badius (Rodentia,
      Spalacidae).
AB  - Cannomys and Rhizomys are the sole living genera of the tribe Rhizomyini
      (Rhizomyinae, Spalacidae, Rodentia), known in the fossil record since the Late
      Miocene. The dental morphology of fossil Rhizomyini has been described in detail
      but until recently such descriptions were unavailable for extant species. A
      detailed account of the morphology and dental wear pattern of the cheek teeth of
      Cannomys badius is provided here based on the examination of museum specimens.
      Three stages of wear are recognized. Cannomys shares with Rhizomys the
      synapomorphy of having a mesolophid that is a long continuation of the protoconid
      on the first lower molar. There are significant differences between these taxa,
      such as the much smaller size of the cheek teeth and the trilophodont dental
      pattern of the M2, M3, and m2 in Cannomys.

PMID- 23166473
TI  - Systematics of the Osteocephalusbuckleyi species complex (Anura, Hylidae) from
      Ecuador and Peru.
AB  - We present a new phylogeny, based on DNA sequences of mitochondrial and nuclear
      genes, for frogs of the genus Osteocephalus with emphasis in the Osteocephalus
      buckleyi species complex. Genetic, morphologic, and advertisement call data are
      combined to define species boundaries and describe new species. The phylogeny
      shows strong support for: (1) a basal position of Osteocephalus taurinus +
      Osteocephalus oophagus, (2) a clade containing phytotelmata breeding species, and
      (3) a clade that corresponds to the Osteocephalus buckleyi species complex. Our
      results document a large proportion of hidden diversity within a set of
      populations that were previously treated as a single, widely distributed species,
      Osteocephalus buckleyi. Individuals assignable to Osteocephalus buckleyi formed a
      paraphyletic group relative to Osteocephalus verruciger and Osteocephalus
      cabrerai and contained four species, one of which is Osteocephalus buckleyisensu
      stricto and three are new. Two of the new species are shared between Ecuador and
      Peru (Osteocephalus vilmaesp. n. and Osteocephalus cannatellaisp. n.) and one is
      distributed in the Amazon region of southern Peru (Osteocephalus germanisp. n.)
      We discuss the difficulties of using morphological characters to define species
      boundaries and propose a hypothesis to explain them.

PMID- 23166474
TI  - Revision of the freshwater genus Atyaephyra (Crustacea, Decapoda, Atyidae) based
      on morphological and molecular data.
AB  - Atyaephyra de Brito Capello, 1867 was described from the Mediterranean region
      almost 200 years ago. Since then, the genus has been recorded from various
      freshwater habitats in Europe, North Africa and the Middle East. Despite its long
      history, the taxonomic status of Atyaephyra species remains confusing and
      uncertain. Consequently numerous specimens from the known range of Atyaephyra
      were analysed using morphological characters and mitochondrial COI sequences in
      an attempt to clarify the taxonomy of this genus. The present study recognises
      seven Atyaephyra species, more than twice as many as previously recorded (three),
      four of which are considered as new. The new species are described, additional
      information to the original descriptions are provided for the remaining three
      taxa, while neotypes of Atyaephyra desmarestii Millet, 1831 and Atyaephyra
      stankoi Karaman, 1972 are designated to stabilize their taxonomy. Non-overlapping
      distinguishing morphological characters are used to discriminate the examined
      material into five species, e.g., Atyaephyra desmarestii, Atyaephyra stankoi,
      Atyaephyra orientalis Bouvier, 1913, Atyaephyra thyamisensissp. n., Atyaephyra
      strymonensissp. n. In addition, the genetic analysis supports the existence of
      multiple phylogenetic clades in the broader Mediterranean area and distinguishes
      two new cryptic species, namely Atyaephyra tuerkayisp. n. and Atyaephyra
      acheronensissp. n. The geographic distribution of these species is confirmed and
      their phylogenetic relationships are described.

PMID- 23166475
TI  - A new fossil cricket of the genus Proanaxipha in Miocene amber from the Dominican
      Republic (Orthoptera, Gryllidae, Pentacentrinae).
AB  - A new species of the cricket genus Proanaxipha Vickery & Poinar (Orthoptera:
      Gryllidae: Pentacentrinae) from Early Miocene Dominican amber is described and
      illustrated. Proanaxipha madgesuttonaesp. n. is distinguished from congeners by:
      (1) head capsule bearing a distinctive posteriorly bilobed colour spot on the
      vertex; (2) presence of crossveins in the proximal part of the mediocubital area;
      (3) apical field of tegmen entirely dark; and (4) median process of epiphallus
      short. The poorly known Proanaxipha bicolorata Vickery & Poinar, of questionable
      affinity and status, is herein regarded as a nomen inquirendum.

PMID- 23166476
TI  - Revision, cladistic analysis and biogeography of Typhochlaena C. L. Koch, 1850,
      Pachistopelma Pocock, 1901 and Iridopelma Pocock, 1901 (Araneae, Theraphosidae,
      Aviculariinae).
AB  - Three aviculariine genera endemic to Brazil are revised. Typhochlaena C. L. Koch,
      1850 is resurrected, including five species; Pachistopelma Pocock, 1901 includes
      two species; and Iridopelma Pocock, 1901, six species. Nine species are newly
      described: Typhochlaena ammasp. n., Typhochlaena costaesp. n., Typhochlaena
      curumimsp. n., Typhochlaena paschoalisp. n., Pachistopelma bromelicolasp. n.,
      Iridopelma katiaesp. n., Iridopelma marcoisp. n., Iridopelma oliveiraisp. n. and
      Iridopelma vaninisp. n. Three new synonymies are established: Avicularia pulchra
      Mello-Leitao, 1933 and Avicularia recifiensis Struchen & Brandle, 1996 are junior
      synonyms of Pachistopelma rufonigrum Pocock, 1901 syn. n., and Avicularia
      palmicola Mello-Leitao, 1945 is a junior synonym of Iridopelma hirsutum Pocock,
      1901 syn. n.Pachistopelma concolor Caporiacco, 1947 is transferred to
      Tapinauchenius Ausserer, 1871, making the new combination Tapinauchenius concolor
      (Caporiacco, 1947)comb. n. Lectotypes are newly designed for Pachistopelma
      rufonigrum Pocock, 1901 , Iridopelma hirsutum Pocock, 1901 and Pachistopelma
      concolor Caporiacco, 1947. Cladistic analyses using both equal and implied
      weights were carried out with a matrix comprising 62 characters and 38 terminal
      taxa. The chosen cladogram found with X-Pee-Wee and concavity 6 suggests they are
      monophyletic. All species are keyed and mapped and information on species habitat
      and area cladograms are presented. Discussion on biogeography and conservation is
      provided.

PMID- 23166477
TI  - A Multi-Domain Self-Report Measure of Coparenting.
AB  - OBJECTIVE: This study reports the psychometric properties of a multi-domain
      measure of the coparenting relationship in dual-parent families.  METHOD: 152
      couples participating in a transition to parenthood study completed the
      Coparenting Relationship Scale and additional measures during home visits at
      child age 6 months, 1 year, and 3 years.  RESULTS: Psychometric and construct
      validity assessments indicated the measure performed satisfactorily. The 35-item
      measure demonstrated good reliability and strong stability. Subscales measuring
      theoretically and empirically important aspects of coparenting (coparenting
      agreement, coparenting closeness, exposure of child to conflict, coparenting
      support, coparenting undermining, endorsement of partner's parenting, and
      division of labor) demonstrated good reliability as well. A 14-item brief overall
      measure showed very strong associations with the overall measure. Relations of
      the full scale with a measure of social desirability were weak, and the full
      scale was positively associated with positive dimensions of the dyadic couple
      relationship (love, sex/romance, couple efficacy) and inversely associated with
      negative dimensions (conflict, ineffective arguing)-as expected.  CONCLUSIONS:
      This initial examination of the Coparenting Relationship Scale suggests that it
      possesses good psychometric properties (reliability, stability, construct
      validity, and inter-rater agreement), can be flexibly administered in short and
      long forms, and is positioned to promote further conceptual and methodological
      progress in the study of coparenting.

PMID- 23166478
TI  - Strategy diversity stabilizes mutualism through investment cycles, phase
      polymorphism, and spatial bubbles.
AB  - There is continuing interest in understanding factors that facilitate the
      evolution and stability of cooperation within and between species. Such
      interactions will often involve plasticity in investment behavior, in response to
      the interacting partner's investments. Our aim here is to investigate the
      evolution and stability of reciprocal investment behavior in interspecific
      interactions, a key phenomenon strongly supported by experimental observations.
      In particular, we present a comprehensive analysis of a continuous reciprocal
      investment game between mutualists, both in well-mixed and spatially structured
      populations, and we demonstrate a series of novel mechanisms for maintaining
      interspecific mutualism. We demonstrate that mutualistic partners invariably
      follow investment cycles, during which mutualism first increases, before both
      partners eventually reduce their investments to zero, so that these cycles always
      conclude with full defection. We show that the key mechanism for stabilizing
      mutualism is phase polymorphism along the investment cycle. Although mutualistic
      partners perpetually change their strategies, the community-level distribution of
      investment levels becomes stationary. In spatially structured populations, the
      maintenance of polymorphism is further facilitated by dynamic mosaic structures,
      in which mutualistic partners form expanding and collapsing spatial bubbles or
      clusters. Additionally, we reveal strategy-diversity thresholds, both for well
      mixed and spatially structured mutualistic communities, and discuss factors for
      meeting these thresholds, and thus maintaining mutualism. Our results demonstrate
      that interspecific mutualism, when considered as plastic investment behavior, can
      be unstable, and, in agreement with empirical observations, may involve a
      polymorphism of investment levels, varying both in space and in time. Identifying
      the mechanisms maintaining such polymorphism, and hence mutualism in natural
      communities, provides a significant step towards understanding the coevolution
      and population dynamics of mutualistic interactions.

PMID- 23166479
TI  - This Deja vu feeling--analysis of multidomain protein evolution in eukaryotic
      genomes.
AB  - Evolutionary innovation in eukaryotes and especially animals is at least
      partially driven by genome rearrangements and the resulting emergence of proteins
      with new domain combinations, and thus potentially novel functionality. Given the
      random nature of such rearrangements, one could expect that proteins with
      particularly useful multidomain combinations may have been rediscovered multiple
      times by parallel evolution. However, existing reports suggest a minimal role of
      this phenomenon in the overall evolution of eukaryotic proteomes. We assembled a
      collection of 172 complete eukaryotic genomes that is not only the largest, but
      also the most phylogenetically complete set of genomes analyzed so far. By
      employing a maximum parsimony approach to compare repertoires of Pfam domains and
      their combinations, we show that independent evolution of domain combinations is
      significantly more prevalent than previously thought. Our results indicate that
      about 25% of all currently observed domain combinations have evolved multiple
      times. Interestingly, this percentage is even higher for sets of domain
      combinations in individual species, with, for instance, 70% of the domain
      combinations found in the human genome having evolved independently at least once
      in other species. We also show that previous, much lower estimates of this rate
      are most likely due to the small number and biased phylogenetic distribution of
      the genomes analyzed. The process of independent emergence of identical domain
      combination is widespread, not limited to domains with specific functional
      categories. Besides data from large-scale analyses, we also present individual
      examples of independent domain combination evolution. The surprisingly large
      contribution of parallel evolution to the development of the domain combination
      repertoire in extant genomes has profound consequences for our understanding of
      the evolution of pathways and cellular processes in eukaryotes and for
      comparative functional genomics.

PMID- 23166480
TI  - Chemotactic migration of T cells towards dendritic cells promotes the detection
      of rare antigens.
AB  - In many immunological processes chemoattraction is thought to play a role in
      guiding cells to their sites of action. However, based on in vivo two-photon
      microscopy experiments in the absence of cognate antigen, T cell migration in
      lymph nodes (LNs) has been roughly described as a random walk. Although it has
      been shown that dendritic cells (DCs) carrying cognate antigen in some
      circumstances attract T cells chemotactically, it is currently still unclear
      whether chemoattraction of T cells towards DCs helps or hampers scanning.
      Chemoattraction towards DCs could on the one hand help T cells to rapidly find
      DCs. On the other hand, it could be deleterious if DCs become shielded by a
      multitude of attracted yet non-specific T cells. Results from a recent simulation
      study suggested that the deleterious effect dominates. We re-addressed the
      question whether T cell chemoattraction towards DCs is expected to promote or
      hamper the detection of rare antigens using the Cellular Potts Model, a formalism
      that allows for dynamic, flexible cellular shapes and cell migration. Our
      simulations show that chemoattraction of T cells enhances the DC scanning
      efficiency, leading to an increased probability that rare antigen-specific T
      cells find DCs carrying cognate antigen. Desensitization of T cells after contact
      with a DC further improves the scanning efficiency, yielding an almost threefold
      enhancement compared to random migration. Moreover, the chemotaxis-driven
      migration still roughly appears as a random walk, hence fine-tuned analysis of
      cell tracks will be required to detect chemotaxis within microscopy data.

PMID- 23166481
TI  - A Bayesian inference framework to reconstruct transmission trees using
      epidemiological and genetic data.
AB  - The accurate identification of the route of transmission taken by an infectious
      agent through a host population is critical to understanding its epidemiology and
      informing measures for its control. However, reconstruction of transmission
      routes during an epidemic is often an underdetermined problem: data about the
      location and timings of infections can be incomplete, inaccurate, and compatible
      with a large number of different transmission scenarios. For fast-evolving
      pathogens like RNA viruses, inference can be strengthened by using genetic data,
      nowadays easily and affordably generated. However, significant statistical
      challenges remain to be overcome in the full integration of these different data
      types if transmission trees are to be reliably estimated. We present here a
      framework leading to a bayesian inference scheme that combines genetic and
      epidemiological data, able to reconstruct most likely transmission patterns and
      infection dates. After testing our approach with simulated data, we apply the
      method to two UK epidemics of Foot-and-Mouth Disease Virus (FMDV): the 2007
      outbreak, and a subset of the large 2001 epidemic. In the first case, we are able
      to confirm the role of a specific premise as the link between the two phases of
      the epidemics, while transmissions more densely clustered in space and time
      remain harder to resolve. When we consider data collected from the 2001 epidemic
      during a time of national emergency, our inference scheme robustly infers
      transmission chains, and uncovers the presence of undetected premises, thus
      providing a useful tool for epidemiological studies in real time. The generation
      of genetic data is becoming routine in epidemiological investigations, but the
      development of analytical tools maximizing the value of these data remains a
      priority. Our method, while applied here in the context of FMDV, is general and
      with slight modification can be used in any situation where both spatiotemporal
      and genetic data are available.

PMID- 23166482
TI  - Elastic energy storage and radial forces in the myofilament lattice depend on
      sarcomere length.
AB  - We most often consider muscle as a motor generating force in the direction of
      shortening, but less often consider its roles as a spring or a brake. Here we
      develop a fully three-dimensional spatially explicit model of muscle to isolate
      the locations of forces and energies that are difficult to separate
      experimentally. We show the strain energy in the thick and thin filaments is less
      than one third the strain energy in attached cross-bridges. This result suggests
      the cross-bridges act as springs, storing energy within muscle in addition to
      generating the force which powers muscle. Comparing model estimates of energy
      consumed to elastic energy stored, we show that the ratio of these two properties
      changes with sarcomere length. The model predicts storage of a greater fraction
      of energy at short sarcomere lengths, suggesting a mechanism by which muscle
      function shifts as force production declines, from motor to spring. Additionally,
      we investigate the force that muscle produces in the radial or transverse
      direction, orthogonal to the direction of shortening. We confirm prior
      experimental estimates that place radial forces on the same order of magnitude as
      axial forces, although we find that radial forces and axial forces vary
      differently with changes in sarcomere length.

PMID- 23166483
TI  - Sensorimotor learning biases choice behavior: a learning neural field model for
      decision making.
AB  - According to a prominent view of sensorimotor processing in primates, selection
      and specification of possible actions are not sequential operations. Rather, a
      decision for an action emerges from competition between different movement plans,
      which are specified and selected in parallel. For action choices which are based
      on ambiguous sensory input, the frontoparietal sensorimotor areas are considered
      part of the common underlying neural substrate for selection and specification of
      action. These areas have been shown capable of encoding alternative spatial motor
      goals in parallel during movement planning, and show signatures of competitive
      value-based selection among these goals. Since the same network is also involved
      in learning sensorimotor associations, competitive action selection (decision
      making) should not only be driven by the sensory evidence and expected reward in
      favor of either action, but also by the subject's learning history of different
      sensorimotor associations. Previous computational models of competitive neural
      decision making used predefined associations between sensory input and
      corresponding motor output. Such hard-wiring does not allow modeling of how
      decisions are influenced by sensorimotor learning or by changing reward
      contingencies. We present a dynamic neural field model which learns arbitrary
      sensorimotor associations with a reward-driven Hebbian learning algorithm. We
      show that the model accurately simulates the dynamics of action selection with
      different reward contingencies, as observed in monkey cortical recordings, and
      that it correctly predicted the pattern of choice errors in a control experiment.
      With our adaptive model we demonstrate how network plasticity, which is required
      for association learning and adaptation to new reward contingencies, can
      influence choice behavior. The field model provides an integrated and dynamic
      account for the operations of sensorimotor integration, working memory and action
      selection required for decision making in ambiguous choice situations.

PMID- 23166484
TI  - Functional connectivity and tuning curves in populations of simultaneously
      recorded neurons.
AB  - How interactions between neurons relate to tuned neural responses is a
      longstanding question in systems neuroscience. Here we use statistical modeling
      and simultaneous multi-electrode recordings to explore the relationship between
      these interactions and tuning curves in six different brain areas. We find that,
      in most cases, functional interactions between neurons provide an explanation of
      spiking that complements and, in some cases, surpasses the influence of canonical
      tuning curves. Modeling functional interactions improves both encoding and
      decoding accuracy by accounting for noise correlations and features of the
      external world that tuning curves fail to capture. In cortex, modeling coupling
      alone allows spikes to be predicted more accurately than tuning curve models
      based on external variables. These results suggest that statistical models of
      functional interactions between even relatively small numbers of neurons may
      provide a useful framework for examining neural coding.

PMID- 23166485
TI  - The dominant folding route minimizes backbone distortion in SH3.
AB  - Energetic frustration in protein folding is minimized by evolution to create a
      smooth and robust energy landscape. As a result the geometry of the native
      structure provides key constraints that shape protein folding mechanisms. Chain
      connectivity in particular has been identified as an essential component for
      realistic behavior of protein folding models. We study the quantitative balance
      of energetic and geometrical influences on the folding of SH3 in a structure
      based model with minimal energetic frustration. A decomposition of the two
      dimensional free energy landscape for the folding reaction into relevant energy
      and entropy contributions reveals that the entropy of the chain is not
      responsible for the folding mechanism. Instead the preferred folding route
      through the transition state arises from a cooperative energetic effect. Off
      pathway structures are penalized by excess distortion in local backbone
      configurations and contact pair distances. This energy cost is a new ingredient
      in the malleable balance of interactions that controls the choice of routes
      during protein folding.

PMID- 23166486
TI  - The origin of minus-end directionality and mechanochemistry of Ncd motors.
AB  - Adaptation of molecular structure to the ligand chemistry and interaction with
      the cytoskeletal filament are key to understanding the mechanochemistry of
      molecular motors. Despite the striking structural similarity with kinesin-1,
      which moves towards plus-end, Ncd motors exhibit minus-end directionality on
      microtubules (MTs). Here, by employing a structure-based model of protein
      folding, we show that a simple repositioning of the neck-helix makes the dynamics
      of Ncd non-processive and minus-end directed as opposed to kinesin-1. Our
      computational model shows that Ncd in solution can have both symmetric and
      asymmetric conformations with disparate ADP binding affinity, also revealing that
      there is a strong correlation between distortion of motor head and decrease in
      ADP binding affinity in the asymmetric state. The nucleotide (NT) free-ADP (phi
      ADP) state bound to MTs favors the symmetric conformation whose coiled-coil stalk
      points to the plus-end. Upon ATP binding, an enhanced flexibility near the head
      neck junction region, which we have identified as the important structural
      element for directional motility, leads to reorienting the coiled-coil stalk
      towards the minus-end by stabilizing the asymmetric conformation. The minus-end
      directionality of the Ncd motor is a remarkable example that demonstrates how
      motor proteins in the kinesin superfamily diversify their functions by simply
      rearranging the structural elements peripheral to the catalytic motor head
      domain.

PMID- 23166487
TI  - Egyptian H5N1 influenza viruses-cause for concern?

PMID- 23166488
TI  - Environmental regulation of prions in yeast.

PMID- 23166489
TI  - Brucella beta 1,2 cyclic glucan is an activator of human and mouse dendritic
      cells.
AB  - Bacterial cyclic glucans are glucose polymers that concentrate within the
      periplasm of alpha-proteobacteria. These molecules are necessary to maintain the
      homeostasis of the cell envelope by contributing to the osmolarity of Gram
      negative bacteria. Here, we demonstrate that Brucella beta 1,2 cyclic glucans are
      potent activators of human and mouse dendritic cells. Dendritic cells activation
      by Brucella beta 1,2 cyclic glucans requires TLR4, MyD88 and TRIF, but not CD14.
      The Brucella cyclic glucans showed neither toxicity nor immunogenicity compared
      to LPS and triggered antigen-specific CD8(+) T cell responses in vivo. These
      cyclic glucans also enhanced antigen-specific CD4(+) and CD8(+) T cell responses
      including cross-presentation by different human DC subsets. Brucella beta 1,2
      cyclic glucans increased the memory CD4(+) T cell responses of blood mononuclear
      cells exposed to recombinant fusion proteins composed of anti-CD40 antibody and
      antigens from both hepatitis C virus and Mycobacterium tuberculosis. Thus cyclic
      glucans represent a new class of adjuvants, which might contribute to the
      development of effective antimicrobial therapies.

PMID- 23166490
TI  - Therapeutic helminth infection of macaques with idiopathic chronic diarrhea
      alters the inflammatory signature and mucosal microbiota of the colon.
AB  - Idiopathic chronic diarrhea (ICD) is a leading cause of morbidity amongst rhesus
      monkeys kept in captivity. Here, we show that exposure of affected animals to the
      whipworm Trichuris trichiura led to clinical improvement in fecal consistency,
      accompanied by weight gain, in four out of the five treated monkeys. By flow
      cytometry analysis of pinch biopsies collected during colonoscopies before and
      after treatment, we found an induction of a mucosal T(H)2 response following
      helminth treatment that was associated with a decrease in activated CD4(+) Ki67+
      cells. In parallel, expression profiling with oligonucleotide microarrays and
      real-time PCR analysis revealed reductions in T(H)1-type inflammatory gene
      expression and increased expression of genes associated with IgE signaling, mast
      cell activation, eosinophil recruitment, alternative activation of macrophages,
      and worm expulsion. By quantifying bacterial 16S rRNA in pinch biopsies using
      real-time PCR analysis, we found reduced bacterial attachment to the intestinal
      mucosa post-treatment. Finally, deep sequencing of bacterial 16S rRNA revealed
      changes to the composition of microbial communities attached to the intestinal
      mucosa following helminth treatment. Thus, the genus Streptophyta of the phylum
      Cyanobacteria was vastly increased in abundance in three out of five ICD monkeys
      relative to healthy controls, but was reduced to control levels post-treatment;
      by contrast, the phylum Tenericutes was expanded post-treatment. These findings
      suggest that helminth treatment in primates can ameliorate colitis by restoring
      mucosal barrier functions and reducing overall bacterial attachment, and also by
      altering the communities of attached bacteria. These results also define ICD in
      monkeys as a tractable preclinical model for ulcerative colitis in which these
      effects can be further investigated.

PMID- 23166491
TI  - The capping domain in RalF regulates effector functions.
AB  - The Legionella pneumophila effector protein RalF functions as a guanine
      nucleotide exchange factor (GEF) that activates the host small GTPase protein ADP
      ribosylation factor (Arf), and recruits this host protein to the vacuoles in
      which this pathogen resides. GEF activity is conferred by the Sec7 domain located
      in the N-terminal region of RalF. Structural studies indicate that the C-terminal
      region of RalF makes contacts with residues in the Sec7 domain important for Arf
      interactions. Theoretically, the C-terminal region of RalF could prevent
      nucleotide exchange activity by blocking the ability of Arf to interact with the
      Sec7 domain. For this reason, the C-terminal region of RalF has been termed a
      capping domain. Here, the role of the RalF capping domain was investigated by
      comparing biochemical and effector activities mediated by this domain in both the
      Legionella RalF protein (LpRalF) and in a RalF ortholog isolated from the
      unrelated intracellular pathogen Rickettsia prowazekii (RpRalF). These data
      indicate that both RalF proteins contain a functional Sec7 domain and that the
      capping domain regulates RalF GEF activity. The capping domain has intrinsic
      determinants that mediate localization of the RalF protein inside of host cells
      and confer distinct effector activities. Localization mediated by the capping
      domain of LpRalF enables the GEF to modulate membrane transport in the secretory
      pathway, whereas, the capping domain of RpRalF enables this bacterial GEF to
      modulate actin dynamics occurring near the plasma membrane. Thus, these data
      reveal that divergence in the function of the C-terminal capping domain alters
      the in vivo functions of the RalF proteins.

PMID- 23166492
TI  - InlA promotes dissemination of Listeria monocytogenes to the mesenteric lymph
      nodes during food borne infection of mice.
AB  - Intestinal Listeria monocytogenes infection is not efficient in mice and this has
      been attributed to a low affinity interaction between the bacterial surface
      protein InlA and E-cadherin on murine intestinal epithelial cells. Previous
      studies using either transgenic mice expressing human E-cadherin or mouse-adapted
      L. monocytogenes expressing a modified InlA protein (InlA(m)) with high affinity
      for murine E-cadherin showed increased efficiency of intragastric infection.
      However, the large inocula used in these studies disseminated to the spleen and
      liver rapidly, resulting in a lethal systemic infection that made it difficult to
      define the natural course of intestinal infection. We describe here a novel mouse
      model of oral listeriosis that closely mimics all phases of human disease: (1)
      ingestion of contaminated food, (2) a distinct period of time during which L.
      monocytogenes colonize only the intestines, (3) varying degrees of systemic
      spread in susceptible vs. resistant mice, and (4) late stage spread to the brain.
      Using this natural feeding model, we showed that the type of food, the time of
      day when feeding occurred, and mouse gender each affected susceptibility to L.
      monocytogenes infection. Co-infection studies using L. monocytogenes strains that
      expressed either a high affinity ligand for E-cadherin (InlA(m)), a low affinity
      ligand (wild type InlA from Lm EGDe), or no InlA (DeltainlA) showed that InlA was
      not required to establish intestinal infection in mice. However, expression of
      InlA(m) significantly increased bacterial persistence in the underlying lamina
      propria and greatly enhanced dissemination to the mesenteric lymph nodes. Thus,
      these studies revealed a previously uncharacterized role for InlA in facilitating
      systemic spread via the lymphatic system after invasion of the gut mucosa.

PMID- 23166493
TI  - Toll-like receptor 8 ligands activate a vitamin D mediated autophagic response
      that inhibits human immunodeficiency virus type 1.
AB  - Toll-like receptors (TLR) are important in recognizing microbial pathogens and
      triggering host innate immune responses, including autophagy, and in the
      mediation of immune activation during human immunodeficiency virus type-1 (HIV)
      infection. We report here that TLR8 activation in human macrophages induces the
      expression of the human cathelicidin microbial peptide (CAMP), the vitamin D
      receptor (VDR) and cytochrome P450, family 27, subfamily B, polypeptide 1
      (CYP27B1), which 1alpha-hydroxylates the inactive form of vitamin D, 25
      hydroxycholecalciferol, into its biologically active metabolite. Moreover, we
      demonstrate using RNA interference, chemical inhibitors and vitamin D deficient
      media that TLR8 agonists inhibit HIV through a vitamin D and CAMP dependent
      autophagic mechanism. These data support an important role for vitamin D in the
      control of HIV infection, and provide a biological explanation for the benefits
      of vitamin D. These findings also provide new insights into potential novel
      targets to prevent and treat HIV infection.

PMID- 23166494
TI  - Aneuploidy and drug resistance in pathogenic fungi.

PMID- 23166495
TI  - Trypanosome motion represents an adaptation to the crowded environment of the
      vertebrate bloodstream.
AB  - Blood is a remarkable habitat: it is highly viscous, contains a dense packaging
      of cells and perpetually flows at velocities varying over three orders of
      magnitude. Only few pathogens endure the harsh physical conditions within the
      vertebrate bloodstream and prosper despite being constantly attacked by host
      antibodies. African trypanosomes are strictly extracellular blood parasites,
      which evade the immune response through a system of antigenic variation and
      incessant motility. How the flagellates actually swim in blood remains to be
      elucidated. Here, we show that the mode and dynamics of trypanosome locomotion
      are a trait of life within a crowded environment. Using high-speed fluorescence
      microscopy and ordered micro-pillar arrays we show that the parasites mode of
      motility is adapted to the density of cells in blood. Trypanosomes are pulled
      forward by the planar beat of the single flagellum. Hydrodynamic flow across the
      asymmetrically shaped cell body translates into its rotational movement.
      Importantly, the presence of particles with the shape, size and spacing of blood
      cells is required and sufficient for trypanosomes to reach maximum forward
      velocity. If the density of obstacles, however, is further increased to resemble
      collagen networks or tissue spaces, the parasites reverse their flagellar beat
      and consequently swim backwards, in this way avoiding getting trapped. In the
      absence of obstacles, this flagellar beat reversal occurs randomly resulting in
      irregular waveforms and apparent cell tumbling. Thus, the swimming behavior of
      trypanosomes is a surprising example of micro-adaptation to life at low Reynolds
      numbers. For a precise physical interpretation, we compare our high-resolution
      microscopic data to results from a simulation technique that combines the method
      of multi-particle collision dynamics with a triangulated surface model. The
      simulation produces a rotating cell body and a helical swimming path, providing a
      functioning simulation method for a microorganism with a complex swimming
      strategy.

PMID- 23166496
TI  - The quorum sensing volatile molecule 2-amino acetophenon modulates host immune
      responses in a manner that promotes life with unwanted guests.
AB  - Increasing evidence indicates that bacterial quorum sensing (QS) signals are
      important mediators of immunomodulation. However, whether microbes utilize these
      immunomodulatory signals to maintain infection remain unclear. Here, we show that
      the Pseudomonas aeruginosa QS-regulated molecule 2-amino acetophenone (2-AA)
      modulates host immune responses in a manner that increases host ability to cope
      with this pathogen. Mice treated with 2-AA prior to infection had a 90% survival
      compared to 10% survival rate observed in the non-pretreated infected mice.
      Whilst 2-AA stimulation activates key innate immune response pathways involving
      mitogen-activated protein kinases (MAPKs), nuclear factor (NF)-kappaB, and pro
      inflammatory cytokines, it attenuates immune response activation upon
      pretreatment, most likely by upregulating anti-inflammatory cytokines. 2-AA host
      pretreatment is characterized by a transcriptionally regulated block of c-JUN N
      terminal kinase (JNK) and NF-kappaB activation, with relatively preserved
      activation of extracellular regulated kinase (ERK) 1/2. These kinase changes lead
      to CCAAT/enhancer-binding protein-beta (c/EBPbeta) activation and formation of
      the c/EBPbeta-p65 complex that prevents NF-kappaB activation. 2-AA's aptitude for
      dampening the inflammatory processes while increasing host survival and pathogen
      persistence concurs with its ability to signal bacteria to switch to a chronic
      infection mode. Our results reveal a QS immunomodulatory signal that promotes
      original aspects of interkingdom communication. We propose that this
      communication facilitates pathogen persistence, while enabling host tolerance to
      infection.

PMID- 23166497
TI  - The mosquito melanization response is implicated in defense against the
      entomopathogenic fungus Beauveria bassiana.
AB  - Mosquito immunity studies have focused mainly on characterizing immune effector
      mechanisms elicited against parasites, bacteria and more recently, viruses.
      However, those elicited against entomopathogenic fungi remain poorly understood,
      despite the ubiquitous nature of these microorganisms and their unique invasion
      route that bypasses the midgut epithelium, an important immune tissue and
      physical barrier. Here, we used the malaria vector Anopheles gambiae as a model
      to investigate the role of melanization, a potent immune effector mechanism of
      arthropods, in mosquito defense against the entomopathogenic fungus Beauveria
      bassiana, using in vivo functional genetic analysis and confocal microscopy. The
      temporal monitoring of fungal growth in mosquitoes injected with B. bassiana
      conidia showed that melanin eventually formed on all stages, including conidia,
      germ tubes and hyphae, except the single cell hyphal bodies. Nevertheless,
      melanin rarely aborted the growth of any of these stages and the mycelium
      continued growing despite being melanized. Silencing TEP1 and CLIPA8, key
      positive regulators of Plasmodium and bacterial melanization in A. gambiae,
      abolished completely melanin formation on hyphae but not on germinating conidia
      or germ tubes. The detection of a layer of hemocytes surrounding germinating
      conidia but not hyphae suggested that melanization of early fungal stages is cell
      mediated while that of late stages is a humoral response dependent on TEP1 and
      CLIPA8. Microscopic analysis revealed specific association of TEP1 with surfaces
      of hyphae and the requirement of both, TEP1 and CLIPA8, for recruiting
      phenoloxidase to these surfaces. Finally, fungal proliferation was more rapid in
      TEP1 and CLIPA8 knockdown mosquitoes which exhibited increased sensitivity to
      natural B. bassiana infections than controls. In sum, the mosquito melanization
      response retards significantly B. bassiana growth and dissemination, a finding
      that may be exploited to design transgenic fungi with more potent bio-control
      activities against mosquitoes.

PMID- 23166498
TI  - Sensitivity of mitochondrial transcription and resistance of RNA polymerase II
      dependent nuclear transcription to antiviral ribonucleosides.
AB  - Ribonucleoside analogues have potential utility as anti-viral, -parasitic, 
      bacterial and -cancer agents. However, their clinical applications have been
      limited by off target effects. Development of antiviral ribonucleosides for
      treatment of hepatitis C virus (HCV) infection has been hampered by appearance of
      toxicity during clinical trials that evaded detection during preclinical studies.
      It is well established that the human mitochondrial DNA polymerase is an off
      target for deoxyribonucleoside reverse transcriptase inhibitors. Here we test the
      hypothesis that triphosphorylated metabolites of therapeutic ribonucleoside
      analogues are substrates for cellular RNA polymerases. We have used
      ribonucleoside analogues with activity against HCV as model compounds for
      therapeutic ribonucleosides. We have included ribonucleoside analogues containing
      2'-C-methyl, 4'-methyl and 4'-azido substituents that are non-obligate chain
      terminators of the HCV RNA polymerase. We show that all of the anti-HCV
      ribonucleoside analogues are substrates for human mitochondrial RNA polymerase
      (POLRMT) and eukaryotic core RNA polymerase II (Pol II) in vitro. Unexpectedly,
      analogues containing 2'-C-methyl, 4'-methyl and 4'-azido substituents were
      inhibitors of POLRMT and Pol II. Importantly, the proofreading activity of TFIIS
      was capable of excising these analogues from Pol II transcripts. Evaluation of
      transcription in cells confirmed sensitivity of POLRMT to antiviral
      ribonucleosides, while Pol II remained predominantly refractory. We introduce a
      parameter termed the mitovir (mitochondrial dysfunction caused by antiviral
      ribonucleoside) score that can be readily obtained during preclinical studies
      that quantifies the mitochondrial toxicity potential of compounds. We suggest the
      possibility that patients exhibiting adverse effects during clinical trials may
      be more susceptible to damage by nucleoside analogs because of defects in
      mitochondrial or nuclear transcription. The paradigm reported here should
      facilitate development of ribonucleosides with a lower potential for toxicity.

PMID- 23166499
TI  - Semaphorin-7A is an erythrocyte receptor for P. falciparum merozoite-specific
      TRAP homolog, MTRAP.
AB  - The motility and invasion of Plasmodium parasites is believed to require a
      cytoplasmic actin-myosin motor associated with a cell surface ligand belonging to
      the TRAP (thrombospondin-related anonymous protein) family. Current models of
      invasion usually invoke the existence of specific receptors for the TRAP-family
      ligands on the surface of the host cell; however, the identities of these
      receptors remain largely unknown. Here, we identify the GPI-linked protein
      Semaphorin-7A (CD108) as an erythrocyte receptor for the P. falciparum merozoite
      specific TRAP homolog (MTRAP) by using a systematic screening approach designed
      to detect extracellular protein interactions. The specificity of the interaction
      was demonstrated by showing that binding was saturable and by quantifying the
      equilibrium and kinetic biophysical binding parameters using surface plasmon
      resonance. We found that two MTRAP monomers interact via their tandem TSR domains
      with the Sema domains of a Semaphorin-7A homodimer. Known naturally-occurring
      polymorphisms in Semaphorin-7A did not quantitatively affect MTRAP binding nor
      did the presence of glycans on the receptor. Attempts to block the interaction
      during in vitro erythrocyte invasion assays using recombinant proteins and
      antibodies showed no significant inhibitory effect, suggesting the
      inaccessibility of the complex to proteinaceous blocking agents. These findings
      now provide important experimental evidence to support the model that parasite
      TRAP-family ligands interact with specific host receptors during cellular
      invasion.

PMID- 23166500
TI  - Tubular structure induced by a plant virus facilitates viral spread in its vector
      insect.
AB  - Rice dwarf virus (RDV) replicates in and is transmitted by a leafhopper vector in
      a persistent-propagative manner. Previous cytopathologic and genetic data
      revealed that tubular structures, constructed by the nonstructural viral protein
      Pns10, contain viral particles and are directly involved in the intercellular
      spread of RDV among cultured leafhopper cells. Here, we demonstrated that RDV
      exploited these virus-containing tubules to move along actin-based microvilli of
      the epithelial cells and muscle fibers of visceral muscle tissues in the
      alimentary canal, facilitating the spread of virus in the body of its insect
      vector leafhoppers. In cultured leafhopper cells, the knockdown of Pns10
      expression due to RNA interference (RNAi) induced by synthesized dsRNA from Pns10
      gene strongly inhibited tubule formation and prevented the spread of virus among
      insect vector cells. RNAi induced after ingestion of dsRNA from Pns10 gene
      strongly inhibited formation of tubules, preventing intercellular spread and
      transmission of the virus by the leafhopper. All these results, for the first
      time, show that a persistent-propagative virus exploits virus-containing tubules
      composed of a nonstructural viral protein to traffic along actin-based cellular
      protrusions, facilitating the intercellular spread of the virus in the vector
      insect. The RNAi strategy and the insect vector cell culture provide useful tools
      to investigate the molecular mechanisms enabling efficient transmission of
      persistent-propagative plant viruses by vector insects.

PMID- 23166501
TI  - Heterotrimeric G-protein signaling is critical to pathogenic processes in
      Entamoeba histolytica.
AB  - Heterotrimeric G-protein signaling pathways are vital components of physiology,
      and many are amenable to pharmacologic manipulation. Here, we identify functional
      heterotrimeric G-protein subunits in Entamoeba histolytica, the causative agent
      of amoebic colitis. The E. histolytica Galpha subunit EhGalpha1 exhibits
      conventional nucleotide cycling properties and is seen to interact with
      EhGbetagamma dimers and a candidate effector, EhRGS-RhoGEF, in typical,
      nucleotide-state-selective fashions. In contrast, a crystal structure of
      EhGalpha1 highlights unique features and classification outside of conventional
      mammalian Galpha subfamilies. E. histolytica trophozoites overexpressing wildtype
      EhGalpha1 in an inducible manner exhibit an enhanced ability to kill host cells
      that may be wholly or partially due to enhanced host cell attachment. EhGalpha1
      overexpressing trophozoites also display enhanced transmigration across a
      Matrigel barrier, an effect that may result from altered baseline migration.
      Inducible expression of a dominant negative EhGalpha1 variant engenders the
      converse phenotypes. Transcriptomic studies reveal that modulation of
      pathogenesis-related trophozoite behaviors by perturbed heterotrimeric G-protein
      expression includes transcriptional regulation of virulence factors and altered
      trafficking of cysteine proteases. Collectively, our studies suggest that E.
      histolytica possesses a divergent heterotrimeric G-protein signaling axis that
      modulates key aspects of cellular processes related to the pathogenesis of this
      infectious organism.

PMID- 23166502
TI  - Inference of population splits and mixtures from genome-wide allele frequency
      data.
AB  - Many aspects of the historical relationships between populations in a species are
      reflected in genetic data. Inferring these relationships from genetic data,
      however, remains a challenging task. In this paper, we present a statistical
      model for inferring the patterns of population splits and mixtures in multiple
      populations. In our model, the sampled populations in a species are related to
      their common ancestor through a graph of ancestral populations. Using genome-wide
      allele frequency data and a Gaussian approximation to genetic drift, we infer the
      structure of this graph. We applied this method to a set of 55 human populations
      and a set of 82 dog breeds and wild canids. In both species, we show that a
      simple bifurcating tree does not fully describe the data; in contrast, we infer
      many migration events. While some of the migration events that we find have been
      detected previously, many have not. For example, in the human data, we infer that
      Cambodians trace approximately 16% of their ancestry to a population ancestral to
      other extant East Asian populations. In the dog data, we infer that both the
      boxer and basenji trace a considerable fraction of their ancestry (9% and 25%,
      respectively) to wolves subsequent to domestication and that East Asian toy
      breeds (the Shih Tzu and the Pekingese) result from admixture between modern toy
      breeds and "ancient" Asian breeds. Software implementing the model described
      here, called TreeMix, is available at http://treemix.googlecode.com.

PMID- 23166503
TI  - A novel human-infection-derived bacterium provides insights into the evolutionary
      origins of mutualistic insect-bacterial symbioses.
AB  - Despite extensive study, little is known about the origins of the mutualistic
      bacterial endosymbionts that inhabit approximately 10% of the world's insects. In
      this study, we characterized a novel opportunistic human pathogen, designated
      "strain HS," and found that it is a close relative of the insect endosymbiont
      Sodalis glossinidius. Our results indicate that ancestral relatives of strain HS
      have served as progenitors for the independent descent of Sodalis-allied
      endosymbionts found in several insect hosts. Comparative analyses indicate that
      the gene inventories of the insect endosymbionts were independently derived from
      a common ancestral template through a combination of irreversible degenerative
      changes. Our results provide compelling support for the notion that mutualists
      evolve from pathogenic progenitors. They also elucidate the role of degenerative
      evolutionary processes in shaping the gene inventories of symbiotic bacteria at a
      very early stage in these mutualistic associations.

PMID- 23166504
TI  - Plant vascular cell division is maintained by an interaction between PXY and
      ethylene signalling.
AB  - The procambium and cambium are meristematic tissues from which vascular tissue is
      derived. Vascular initials differentiate into phloem towards the outside of the
      stem and xylem towards the inside. A small peptide derived from CLV-3/ESR1-LIKE
      41 (CLE41) is thought to promote cell divisions in vascular meristems by
      signalling through the PHLOEM INTERCALLATED WITH XYLEM (PXY) receptor kinase. pxy
      mutants, however, display only small reductions in vascular cell number,
      suggesting a mechanism exists that allows plants to compensate for the absence of
      PXY. Consistent with this idea, we identify a large number of genes specifically
      upregulated in pxy mutants, including several AP2/ERF transcription factors.
      These transcription factors are required for normal cell division in the cambium
      and procambium. These same transcription factors are also upregulated by ethylene
      and in ethylene-overproducing eto1 mutants. eto1 mutants also exhibit an increase
      in vascular cell division that is dependent upon the function of at least 2 of
      these ERF genes. Furthermore, blocking ethylene signalling using a variety of
      ethylene insensitive mutants such as ein2 enhances the cell division defect of
      pxy. Our results suggest that these factors define a novel pathway that acts in
      parallel to PXY/CLE41 to regulate cell division in developing vascular tissue. We
      propose a model whereby vascular cell division is regulated both by PXY
      signalling and ethylene/ERF signalling. Under normal circumstances, however, PXY
      signalling acts to repress the ethylene/ERF pathway.

PMID- 23166505
TI  - C. elegans dopaminergic D2-like receptors delimit recurrent cholinergic-mediated
      motor programs during a goal-oriented behavior.
AB  - Caenorhabditis elegans male copulation requires coordinated temporal-spatial
      execution of different motor outputs. During mating, a cloacal circuit consisting
      of cholinergic sensory-motor neurons and sex muscles maintains the male's
      position and executes copulatory spicule thrusts at his mate's vulva. However,
      distinct signaling mechanisms that delimit these behaviors to their proper
      context are unclear. We found that dopamine (DA) signaling directs copulatory
      spicule insertion attempts to the hermaphrodite vulva by dampening spurious
      stimulus-independent sex muscle contractions. From pharmacology and genetic
      analyses, DA antagonizes stimulatory ACh signaling via the D2-like receptors, DOP
      2 and DOP-3, and Galpha(o/i) proteins, GOA-1 and GPA-7. Calcium imaging and
      optogenetics suggest that heightened DA-expressing ray neuron activities coincide
      with the cholinergic cloacal ganglia function during spicule insertion attempts.
      D2-like receptor signaling also attenuates the excitability of additional mating
      circuits to reduce the duration of mating attempts with unproductive and/or
      inappropriate partners. This suggests that, during wild-type mating, simultaneous
      DA-ACh signaling modulates the activity threshold of repetitive motor programs,
      thus confining the behavior to the proper situational context.

PMID- 23166507
TI  - Genomic study of RNA polymerase II and III SNAPc-bound promoters reveals a gene
      transcribed by both enzymes and a broad use of common activators.
AB  - SNAP(c) is one of a few basal transcription factors used by both RNA polymerase
      (pol) II and pol III. To define the set of active SNAP(c)-dependent promoters in
      human cells, we have localized genome-wide four SNAP(c) subunits, GTF2B (TFIIB),
      BRF2, pol II, and pol III. Among some seventy loci occupied by SNAP(c) and other
      factors, including pol II snRNA genes, pol III genes with type 3 promoters, and a
      few un-annotated loci, most are primarily occupied by either pol II and GTF2B, or
      pol III and BRF2. A notable exception is the RPPH1 gene, which is occupied by
      significant amounts of both polymerases. We show that the large majority of
      SNAP(c)-dependent promoters recruit POU2F1 and/or ZNF143 on their enhancer
      region, and a subset also recruits GABP, a factor newly implicated in SNAP(c)
      dependent transcription. These activators associate with pol II and III promoters
      in G1 slightly before the polymerase, and ZNF143 is required for efficient
      transcription initiation complex assembly. The results characterize a set of
      genes with unique properties and establish that polymerase specificity is not
      absolute in vivo.

PMID- 23166506
TI  - Disruption of mouse Cenpj, a regulator of centriole biogenesis, phenocopies
      Seckel syndrome.
AB  - Disruption of the centromere protein J gene, CENPJ (CPAP, MCPH6, SCKL4), which is
      a highly conserved and ubiquitiously expressed centrosomal protein, has been
      associated with primary microcephaly and the microcephalic primordial dwarfism
      disorder Seckel syndrome. The mechanism by which disruption of CENPJ causes the
      proportionate, primordial growth failure that is characteristic of Seckel
      syndrome is unknown. By generating a hypomorphic allele of Cenpj, we have
      developed a mouse (Cenpj(tm/tm)) that recapitulates many of the clinical features
      of Seckel syndrome, including intrauterine dwarfism, microcephaly with memory
      impairment, ossification defects, and ocular and skeletal abnormalities, thus
      providing clear confirmation that specific mutations of CENPJ can cause Seckel
      syndrome. Immunohistochemistry revealed increased levels of DNA damage and
      apoptosis throughout Cenpj(tm/tm) embryos and adult mice showed an elevated
      frequency of micronucleus induction, suggesting that Cenpj-deficiency results in
      genomic instability. Notably, however, genomic instability was not the result of
      defective ATR-dependent DNA damage signaling, as is the case for the majority of
      genes associated with Seckel syndrome. Instead, Cenpj(tm/tm) embryonic
      fibroblasts exhibited irregular centriole and centrosome numbers and mono- and
      multipolar spindles, and many were near-tetraploid with numerical and structural
      chromosomal abnormalities when compared to passage-matched wild-type cells.
      Increased cell death due to mitotic failure during embryonic development is
      likely to contribute to the proportionate dwarfism that is associated with CENPJ
      Seckel syndrome.

PMID- 23166508
TI  - Biochemical diversification through foreign gene expression in bdelloid rotifers.
AB  - Bdelloid rotifers are microinvertebrates with unique characteristics: they have
      survived tens of millions of years without sexual reproduction; they withstand
      extreme desiccation by undergoing anhydrobiosis; and they tolerate very high
      levels of ionizing radiation. Recent evidence suggests that subtelomeric regions
      of the bdelloid genome contain sequences originating from other organisms by
      horizontal gene transfer (HGT), of which some are known to be transcribed.
      However, the extent to which foreign gene expression plays a role in bdelloid
      physiology is unknown. We address this in the first large scale analysis of the
      transcriptome of the bdelloid Adineta ricciae: cDNA libraries from hydrated and
      desiccated bdelloids were subjected to massively parallel sequencing and
      assembled transcripts compared against the UniProtKB database by blastx to
      identify their putative products. Of ~29,000 matched transcripts, ~10% were
      inferred from blastx matches to be horizontally acquired, mainly from eubacteria
      but also from fungi, protists, and algae. After allowing for possible sources of
      error, the rate of HGT is at least 8%-9%, a level significantly higher than other
      invertebrates. We verified their foreign nature by phylogenetic analysis and by
      demonstrating linkage of foreign genes with metazoan genes in the bdelloid
      genome. Approximately 80% of horizontally acquired genes expressed in bdelloids
      code for enzymes, and these represent 39% of enzymes in identified pathways. Many
      enzymes encoded by foreign genes enhance biochemistry in bdelloids compared to
      other metazoans, for example, by potentiating toxin degradation or generation of
      antioxidants and key metabolites. They also supplement, and occasionally
      potentially replace, existing metazoan functions. Bdelloid rotifers therefore
      express horizontally acquired genes on a scale unprecedented in animals, and
      foreign genes make a profound contribution to their metabolism. This represents a
      potential mechanism for ancient asexuals to adapt rapidly to changing
      environments and thereby persist over long evolutionary time periods in the
      absence of sex.

PMID- 23166509
TI  - Controls of nucleosome positioning in the human genome.
AB  - Nucleosomes are important for gene regulation because their arrangement on the
      genome can control which proteins bind to DNA. Currently, few human nucleosomes
      are thought to be consistently positioned across cells; however, this has been
      difficult to assess due to the limited resolution of existing data. We performed
      paired-end sequencing of micrococcal nuclease-digested chromatin (MNase-seq) from
      seven lymphoblastoid cell lines and mapped over 3.6 billion MNase-seq fragments
      to the human genome to create the highest-resolution map of nucleosome occupancy
      to date in a human cell type. In contrast to previous results, we find that most
      nucleosomes have more consistent positioning than expected by chance and a
      substantial fraction (8.7%) of nucleosomes have moderate to strong positioning.
      In aggregate, nucleosome sequences have 10 bp periodic patterns in dinucleotide
      frequency and DNase I sensitivity; and, across cells, nucleosomes frequently have
      translational offsets that are multiples of 10 bp. We estimate that almost half
      of the genome contains regularly spaced arrays of nucleosomes, which are enriched
      in active chromatin domains. Single nucleotide polymorphisms that reduce DNase I
      sensitivity can disrupt the phasing of nucleosome arrays, which indicates that
      they often result from positioning against a barrier formed by other proteins.
      However, nucleosome arrays can also be created by DNA sequence alone. The most
      striking example is an array of over 400 nucleosomes on chromosome 12 that is
      created by tandem repetition of sequences with strong positioning properties. In
      summary, a large fraction of nucleosomes are consistently positioned--in some
      regions because they adopt favored sequence positions, and in other regions
      because they are forced into specific arrangements by chromatin remodeling or DNA
      binding proteins.

PMID- 23166510
TI  - Blockade of pachytene piRNA biogenesis reveals a novel requirement for
      maintaining post-meiotic germline genome integrity.
AB  - Piwi-interacting RNAs are a diverse class of small non-coding RNAs implicated in
      the silencing of transposable elements and the safeguarding of genome integrity.
      In mammals, male germ cells express two genetically and developmentally distinct
      populations of piRNAs at the pre-pachytene and pachytene stages of meiosis,
      respectively. Pre-pachytene piRNAs are mostly derived from retrotransposons and
      required for their silencing. In contrast, pachytene piRNAs originate from ~3,000
      genomic clusters, and their biogenesis and function remain enigmatic. Here, we
      report that conditional inactivation of the putative RNA helicase MOV10L1 in
      mouse spermatocytes produces a specific loss of pachytene piRNAs, significant
      accumulation of pachytene piRNA precursor transcripts, and unusual polar
      conglomeration of Piwi proteins with mitochondria. Pachytene piRNA-deficient
      spermatocytes progress through meiosis without derepression of LINE1
      retrotransposons, but become arrested at the post-meiotic round spermatid stage
      with massive DNA damage. Our results demonstrate that MOV10L1 acts upstream of
      Piwi proteins in the primary processing of pachytene piRNAs and suggest that,
      distinct from pre-pachytene piRNAs, pachytene piRNAs fulfill a unique function in
      maintaining post-meiotic genome integrity.

PMID- 23166511
TI  - Lessons from model organisms: phenotypic robustness and missing heritability in
      complex disease.
AB  - Genetically tractable model organisms from phages to mice have taught us
      invaluable lessons about fundamental biological processes and disease-causing
      mutations. Owing to technological and computational advances, human biology and
      the causes of human diseases have become accessible as never before. Progress in
      identifying genetic determinants for human diseases has been most remarkable for
      Mendelian traits. In contrast, identifying genetic determinants for complex
      diseases such as diabetes, cancer, and cardiovascular and neurological diseases
      has remained challenging, despite the fact that these diseases cluster in
      families. Hundreds of variants associated with complex diseases have been found
      in genome-wide association studies (GWAS), yet most of these variants explain
      only a modest amount of the observed heritability, a phenomenon known as "missing
      heritability." The missing heritability has been attributed to many factors,
      mainly inadequacies in genotyping and phenotyping. We argue that lessons learned
      about complex traits in model organisms offer an alternative explanation for
      missing heritability in humans. In diverse model organisms, phenotypic robustness
      differs among individuals, and those with decreased robustness show increased
      penetrance of mutations and express previously cryptic genetic variation. We
      propose that phenotypic robustness also differs among humans and that individuals
      with lower robustness will be more responsive to genetic and environmental
      perturbations and hence susceptible to disease. Phenotypic robustness is a
      quantitative trait that can be accurately measured in model organisms, but not as
      yet in humans. We propose feasible approaches to measure robustness in large
      human populations, proof-of-principle experiments for robustness markers in model
      organisms, and a new GWAS design that takes differences in robustness into
      account.

PMID- 23166512
TI  - Genome-wide association studies reveal a simple genetic basis of resistance to
      naturally coevolving viruses in Drosophila melanogaster.
AB  - Variation in susceptibility to infectious disease often has a substantial genetic
      component in animal and plant populations. We have used genome-wide association
      studies (GWAS) in Drosophila melanogaster to identify the genetic basis of
      variation in susceptibility to viral infection. We found that there is
      substantially more genetic variation in susceptibility to two viruses that
      naturally infect D. melanogaster (DCV and DMelSV) than to two viruses isolated
      from other insects (FHV and DAffSV). Furthermore, this increased variation is
      caused by a small number of common polymorphisms that have a major effect on
      resistance and can individually explain up to 47% of the heritability in disease
      susceptibility. For two of these polymorphisms, it has previously been shown that
      they have been driven to a high frequency by natural selection. An advantage of
      GWAS in Drosophila is that the results can be confirmed experimentally. We
      verified that a gene called pastrel--which was previously not known to have an
      antiviral function--is associated with DCV-resistance by knocking down its
      expression by RNAi. Our data suggest that selection for resistance to infectious
      disease can increase genetic variation by increasing the frequency of major
      effect alleles, and this has resulted in a simple genetic basis to variation in
      virus resistance.

PMID- 23166513
TI  - RHOA is a modulator of the cholesterol-lowering effects of statin.
AB  - Although statin drugs are generally efficacious for lowering plasma LDL
      cholesterol levels, there is considerable variability in response. To identify
      candidate genes that may contribute to this variation, we used an unbiased genome
      wide filter approach that was applied to 10,149 genes expressed in immortalized
      lymphoblastoid cell lines (LCLs) derived from 480 participants of the Cholesterol
      and Pharmacogenomics (CAP) clinical trial of simvastatin. The criteria for
      identification of candidates included genes whose statin-induced changes in
      expression were correlated with change in expression of HMGCR, a key regulator of
      cellular cholesterol metabolism and the target of statin inhibition. This
      analysis yielded 45 genes, from which RHOA was selected for follow-up because it
      has been found to participate in mediating the pleiotropic but not the lipid
      lowering effects of statin treatment. RHOA knock-down in hepatoma cell lines
      reduced HMGCR, LDLR, and SREBF2 mRNA expression and increased intracellular
      cholesterol ester content as well as apolipoprotein B (APOB) concentrations in
      the conditioned media. Furthermore, inter-individual variation in statin-induced
      RHOA mRNA expression measured in vitro in CAP LCLs was correlated with the
      changes in plasma total cholesterol, LDL-cholesterol, and APOB induced by
      simvastatin treatment (40 mg/d for 6 wk) of the individuals from whom these cell
      lines were derived. Moreover, the minor allele of rs11716445, a SNP located in a
      novel cryptic RHOA exon, dramatically increased inclusion of the exon in RHOA
      transcripts during splicing and was associated with a smaller LDL-cholesterol
      reduction in response to statin treatment in 1,886 participants from the CAP and
      Pravastatin Inflamation and CRP Evaluation (PRINCE; pravastatin 40 mg/d) statin
      clinical trials. Thus, an unbiased filter approach based on transcriptome-wide
      profiling identified RHOA as a gene contributing to variation in LDL-cholesterol
      response to statin, illustrating the power of this approach for identifying
      candidate genes involved in drug response phenotypes.

PMID- 23166514
TI  - Lamin b1 polymorphism influences morphology of the nuclear envelope, cell cycle
      progression, and risk of neural tube defects in mice.
AB  - Neural tube defects (NTDs), including spina bifida and anencephaly, are common
      birth defects whose complex multigenic causation has hampered efforts to
      delineate their molecular basis. The effect of putative modifier genes in
      determining NTD susceptibility may be investigated in mouse models, particularly
      those that display partial penetrance such as curly tail, a strain in which NTDs
      result from a hypomorphic allele of the grainyhead-like-3 gene. Through proteomic
      analysis, we found that the curly tail genetic background harbours a polymorphic
      variant of lamin B1, lacking one of a series of nine glutamic acid residues.
      Lamins are intermediate filament proteins of the nuclear lamina with multiple
      functions that influence nuclear structure, cell cycle properties, and
      transcriptional regulation. Fluorescence loss in photobleaching showed that the
      variant lamin B1 exhibited reduced stability in the nuclear lamina. Genetic
      analysis demonstrated that the variant also affects neural tube closure: the
      frequency of spina bifida and anencephaly was reduced three-fold when wild-type
      lamin B1 was bred into the curly tail strain background. Cultured fibroblasts
      expressing variant lamin B1 show significantly increased nuclear dysmorphology
      and diminished proliferative capacity, as well as premature senescence,
      associated with reduced expression of cyclins and Smc2, and increased expression
      of p16. The cellular basis of spinal NTDs in curly tail embryos involves a
      proliferation defect localised to the hindgut epithelium, and S-phase progression
      was diminished in the hindgut of embryos expressing variant lamin B1. These
      observations indicate a mechanistic link between altered lamin B1 function,
      exacerbation of the Grhl3-mediated cell proliferation defect, and enhanced
      susceptibility to NTDs. We conclude that lamin B1 is a modifier gene of major
      effect for NTDs resulting from loss of Grhl3 function, a role that is likely
      mediated via the key function of lamin B1 in maintaining integrity of the nuclear
      envelope and ensuring normal cell cycle progression.

PMID- 23166515
TI  - HP1a recruitment to promoters is independent of H3K9 methylation in Drosophila
      melanogaster.
AB  - Heterochromatin protein 1 (HP1) proteins, recognized readers of the
      heterochromatin mark methylation of histone H3 lysine 9 (H3K9me), are important
      regulators of heterochromatin-mediated gene silencing and chromosome structure.
      In Drosophila melanogaster three histone lysine methyl transferases (HKMTs) are
      associated with the methylation of H3K9: Su(var)3-9, Setdb1, and G9a. To probe
      the dependence of HP1a binding on H3K9me, its dependence on these three HKMTs,
      and the division of labor between the HKMTs, we have examined correlations
      between HP1a binding and H3K9me patterns in wild type and null mutants of these
      HKMTs. We show here that Su(var)3-9 controls H3K9me-dependent binding of HP1a in
      pericentromeric regions, while Setdb1 controls it in cytological region 2L:31 and
      (together with POF) in chromosome 4. HP1a binds to the promoters and within
      bodies of active genes in these three regions. More importantly, however, HP1a
      binding at promoters of active genes is independent of H3K9me and POF. Rather, it
      is associated with heterochromatin protein 2 (HP2) and open chromatin. Our
      results support a hypothesis in which HP1a nucleates with high affinity
      independently of H3K9me in promoters of active genes and then spreads via H3K9
      methylation and transient looping contacts with those H3K9me target sites.

PMID- 23166517
TI  - A spatial and temporal gradient of Fgf differentially regulates distinct stages
      of neural development in the zebrafish inner ear.
AB  - Neuroblasts of the statoacoustic ganglion (SAG) initially form in the floor of
      the otic vesicle during a relatively brief developmental window. They soon
      delaminate and undergo a protracted phase of proliferation and migration (transit
      amplification). Neuroblasts eventually differentiate and extend processes bi
      directionally to synapse with hair cells in the inner ear and various targets in
      the hindbrain. Our studies in zebrafish have shown that Fgf signaling controls
      multiple phases of this complex developmental process. Moderate levels of Fgf in
      a gradient emanating from the nascent utricular macula specify SAG neuroblasts in
      laterally adjacent otic epithelium. At a later stage, differentiating SAG neurons
      express Fgf5, which serves two functions: First, as SAG neurons accumulate,
      increasing levels of Fgf exceed an upper threshold that terminates the initial
      phase of neuroblast specification. Second, elevated Fgf delays differentiation of
      transit-amplifying cells, balancing the rate of progenitor renewal with neuronal
      differentiation. Laser-ablation of mature SAG neurons abolishes feedback
      inhibition and causes precocious neuronal differentiation. Similar effects are
      obtained by Fgf5-knockdown or global impairment of Fgf signaling, whereas Fgf
      misexpression has the opposite effect. Thus Fgf signaling renders SAG development
      self-regulating, ensuring steady production of an appropriate number of neurons
      as the larva grows.

PMID- 23166516
TI  - Genome, functional gene annotation, and nuclear transformation of the heterokont
      oleaginous alga Nannochloropsis oceanica CCMP1779.
AB  - Unicellular marine algae have promise for providing sustainable and scalable
      biofuel feedstocks, although no single species has emerged as a preferred
      organism. Moreover, adequate molecular and genetic resources prerequisite for the
      rational engineering of marine algal feedstocks are lacking for most candidate
      species. Heterokonts of the genus Nannochloropsis naturally have high cellular
      oil content and are already in use for industrial production of high-value lipid
      products. First success in applying reverse genetics by targeted gene replacement
      makes Nannochloropsis oceanica an attractive model to investigate the cell and
      molecular biology and biochemistry of this fascinating organism group. Here we
      present the assembly of the 28.7 Mb genome of N. oceanica CCMP1779. RNA
      sequencing data from nitrogen-replete and nitrogen-depleted growth conditions
      support a total of 11,973 genes, of which in addition to automatic annotation
      some were manually inspected to predict the biochemical repertoire for this
      organism. Among others, more than 100 genes putatively related to lipid
      metabolism, 114 predicted transcription factors, and 109 transcriptional
      regulators were annotated. Comparison of the N. oceanica CCMP1779 gene repertoire
      with the recently published N. gaditana genome identified 2,649 genes likely
      specific to N. oceanica CCMP1779. Many of these N. oceanica-specific genes have
      putative orthologs in other species or are supported by transcriptional evidence.
      However, because similarity-based annotations are limited, functions of most of
      these species-specific genes remain unknown. Aside from the genome sequence and
      its analysis, protocols for the transformation of N. oceanica CCMP1779 are
      provided. The availability of genomic and transcriptomic data for Nannochloropsis
      oceanica CCMP1779, along with efficient transformation protocols, provides a
      blueprint for future detailed gene functional analysis and genetic engineering of
      Nannochloropsis species by a growing academic community focused on this genus.

PMID- 23166518
TI  - Evolution of minimal specificity and promiscuity in steroid hormone receptors.
AB  - Most proteins are regulated by physical interactions with other molecules; some
      are highly specific, but others interact with many partners. Despite much
      speculation, we know little about how and why specificity/promiscuity evolves in
      natural proteins. It is widely assumed that specific proteins evolved from more
      promiscuous ancient forms and that most proteins' specificity has been tuned to
      an optimal state by selection. Here we use ancestral protein reconstruction to
      trace the evolutionary history of ligand recognition in the steroid hormone
      receptors (SRs), a family of hormone-regulated animal transcription factors. We
      resurrected the deepest ancestral proteins in the SR family and characterized the
      structure-activity relationships by which they distinguished among ligands. We
      found that that the most ancient split in SR evolution involved a discrete switch
      from an ancient receptor for aromatized estrogens--including xenobiotics--to a
      derived receptor that recognized non-aromatized progestagens and corticosteroids.
      The family's history, viewed in relation to the evolution of their ligands,
      suggests that SRs evolved according to a principle of minimal specificity: at
      each point in time, receptors evolved ligand recognition criteria that were just
      specific enough to parse the set of endogenous substances to which they were
      exposed. By studying the atomic structures of resurrected SR proteins, we found
      that their promiscuity evolved because the ancestral binding cavity was larger
      than the primary ligand and contained excess hydrogen bonding capacity, allowing
      adventitious recognition of larger molecules with additional functional groups.
      Our findings provide an historical explanation for the sensitivity of modern SRs
      to natural and synthetic ligands--including endocrine-disrupting drugs and
      pollutants--and show that knowledge of history can contribute to ligand
      prediction. They suggest that SR promiscuity may reflect the limited power of
      selection within real biological systems to discriminate between perfect and
      "good enough."

PMID- 23166519
TI  - A unified method for detecting secondary trait associations with rare variants:
      application to sequence data.
AB  - Next-generation sequencing has made possible the detection of rare variant (RV)
      associations with quantitative traits (QT). Due to high sequencing cost, many
      studies can only sequence a modest number of selected samples with extreme QT.
      Therefore association testing in individual studies can be underpowered. Besides
      the primary trait, many clinically important secondary traits are often measured.
      It is highly beneficial if multiple studies can be jointly analyzed for detecting
      associations with commonly measured traits. However, analyzing secondary traits
      in selected samples can be biased if sample ascertainment is not properly
      modeled. Some methods exist for analyzing secondary traits in selected samples,
      where some burden tests can be implemented. However p-values can only be
      evaluated analytically via asymptotic approximations, which may not be accurate.
      Additionally, potentially more powerful sequence kernel association tests,
      variable selection-based methods, and burden tests that require permutations
      cannot be incorporated. To overcome these limitations, we developed a unified
      method for analyzing secondary trait associations with RVs (STAR) in selected
      samples, incorporating all RV tests. Statistical significance can be evaluated
      either through permutations or analytically. STAR makes it possible to apply more
      powerful RV tests to analyze secondary trait associations. It also enables
      jointly analyzing multiple cohorts ascertained under different study designs,
      which greatly boosts power. The performance of STAR and commonly used RV
      association tests were comprehensively evaluated using simulation studies. STAR
      was also implemented to analyze a dataset from the SardiNIA project where samples
      with extreme low-density lipoprotein levels were sequenced. A significant
      association between LDLR and systolic blood pressure was identified, which is
      supported by pharmacogenetic studies. In summary, for sequencing studies, STAR is
      an important tool for detecting secondary-trait RV associations.

PMID- 23166520
TI  - The contributions of wobbling and superwobbling to the reading of the genetic
      code.
AB  - Reduced bacterial genomes and most genomes of cell organelles (chloroplasts and
      mitochondria) do not encode the full set of 32 tRNA species required to read all
      triplets of the genetic code according to the conventional wobble rules.
      Superwobbling, in which a single tRNA species that contains a uridine in the
      wobble position of the anticodon reads an entire four-fold degenerate codon box,
      has been suggested as a possible mechanism for how tRNA sets can be reduced.
      However, the general feasibility of superwobbling and its efficiency in the
      various codon boxes have remained unknown. Here we report a complete experimental
      assessment of the decoding rules in a typical prokaryotic genetic system, the
      plastid genome. By constructing a large set of transplastomic knock-out mutants
      for pairs of isoaccepting tRNA species, we show that superwobbling occurs in all
      codon boxes where it is theoretically possible. Phenotypic characterization of
      the transplastomic mutant plants revealed that the efficiency of superwobbling
      varies in a codon box-dependent manner, but--contrary to previous suggestions--it
      is independent of the number of hydrogen bonds engaged in codon-anticodon
      interaction. Finally, our data provide experimental evidence of the minimum tRNA
      set comprising 25 tRNA species, a number lower than previously suggested. Our
      results demonstrate that all triplets with pyrimidines in third codon position
      are dually decoded: by a tRNA species utilizing standard base pairing or wobbling
      and by a second tRNA species employing superwobbling. This has important
      implications for the interpretation of the genetic code and will aid the
      construction of synthetic genomes with a minimum-size translational apparatus.

PMID- 23166521
TI  - Polyadenylation-dependent control of long noncoding RNA expression by the poly(A)
      binding protein nuclear 1.
AB  - The poly(A)-binding protein nuclear 1 (PABPN1) is a ubiquitously expressed
      protein that is thought to function during mRNA poly(A) tail synthesis in the
      nucleus. Despite the predicted role of PABPN1 in mRNA polyadenylation, little is
      known about the impact of PABPN1 deficiency on human gene expression.
      Specifically, it remains unclear whether PABPN1 is required for general mRNA
      expression or for the regulation of specific transcripts. Using RNA sequencing
      (RNA-seq), we show here that the large majority of protein-coding genes express
      normal levels of mRNA in PABPN1-deficient cells, arguing that PABPN1 may not be
      required for the bulk of mRNA expression. Unexpectedly, and contrary to the view
      that PABPN1 functions exclusively at protein-coding genes, we identified a class
      of PABPN1-sensitive long noncoding RNAs (lncRNAs), the majority of which
      accumulated in conditions of PABPN1 deficiency. Using the spliced transcript
      produced from a snoRNA host gene as a model lncRNA, we show that PABPN1 promotes
      lncRNA turnover via a polyadenylation-dependent mechanism. PABPN1-sensitive
      lncRNAs are targeted by the exosome and the RNA helicase MTR4/SKIV2L2; yet, the
      polyadenylation activity of TRF4-2, a putative human TRAMP subunit, appears to be
      dispensable for PABPN1-dependent regulation. In addition to identifying a novel
      function for PABPN1 in lncRNA turnover, our results provide new insights into the
      post-transcriptional regulation of human lncRNAs.

PMID- 23166522
TI  - Comparison of mitochondrial mutation spectra in ageing human colonic epithelium
      and disease: absence of evidence for purifying selection in somatic mitochondrial
      DNA point mutations.
AB  - Human ageing has been predicted to be caused by the accumulation of molecular
      damage in cells and tissues. Somatic mitochondrial DNA (mtDNA) mutations have
      been documented in a number of ageing tissues and have been shown to be
      associated with cellular mitochondrial dysfunction. It is unknown whether there
      are selective constraints, which have been shown to occur in the germline, on the
      occurrence and expansion of these mtDNA mutations within individual somatic
      cells. Here we compared the pattern and spectrum of mutations observed in ageing
      human colon to those observed in the general population (germline variants) and
      those associated with primary mtDNA disease. The pathogenicity of the protein
      encoding mutations was predicted using a computational programme, MutPred, and
      the scores obtained for the three groups compared. We show that the mutations
      associated with ageing are randomly distributed throughout the genome, are more
      frequently non-synonymous or frameshift mutations than the general population,
      and are significantly more pathogenic than population variants. Mutations
      associated with primary mtDNA disease were significantly more pathogenic than
      ageing or population mutations. These data provide little evidence for any
      selective constraints on the occurrence and expansion of mtDNA mutations in
      somatic cells of the human colon during human ageing in contrast to germline
      mutations seen in the general population.

PMID- 23166523
TI  - Histone methyltransferases MES-4 and MET-1 promote meiotic checkpoint activation
      in Caenorhabditis elegans.
AB  - Chromosomes that fail to synapse during meiosis become enriched for chromatin
      marks associated with heterochromatin assembly. This response, called meiotic
      silencing of unsynapsed or unpaired chromatin (MSUC), is conserved from fungi to
      mammals. In Caenorhabditis elegans, unsynapsed chromosomes also activate a
      meiotic checkpoint that monitors synapsis. The synapsis checkpoint signal is
      dependent on cis-acting loci called Pairing Centers (PCs). How PCs signal to
      activate the synapsis checkpoint is currently unknown. We show that a chromosomal
      duplication with PC activity is sufficient to activate the synapsis checkpoint
      and that it undergoes heterochromatin assembly less readily than a duplication of
      a non-PC region, suggesting that the chromatin state of these loci is important
      for checkpoint function. Consistent with this hypothesis, MES-4 and MET-1,
      chromatin-modifying enzymes associated with transcriptional activity, are
      required for the synapsis checkpoint. In addition, a duplication with PC activity
      undergoes heterochromatin assembly when mes-4 activity is reduced. MES-4 function
      is required specifically for the X chromosome, while MES-4 and MET-1 act
      redundantly to monitor autosomal synapsis. We propose that MES-4 and MET-1
      antagonize heterochromatin assembly at PCs of unsynapsed chromosomes by promoting
      a transcriptionally permissive chromatin environment that is required for meiotic
      checkpoint function. Moreover, we suggest that different genetic requirements to
      monitor the behavior of sex chromosomes and autosomes allow for the lone
      unsynapsed X present in male germlines to be shielded from inappropriate
      checkpoint activation.

PMID- 23166524
TI  - Human population admixture in Asia.
AB  - Genetic admixture in human, the result of inter-marriage among people from
      different well-differentiated populations, has been extensively studied in the
      New World, where European colonization brought contact between peoples of Europe,
      Africa, and Asia and the Amerindian populations. In Asia, genetic admixing has
      been also prevalent among previously separated human populations. However,
      studies on admixed populations in Asia have been largely underrepresented in
      similar efforts in the New World. Here, I will provide an overview of population
      genomic studies that have been published to date on human admixture in Asia,
      focusing on population structure and population history.

PMID- 23166525
TI  - Characterization of Chromatin Structure-associated Histone Modifications in
      Breast Cancer Cells.
AB  - Chromatin structure and dynamics that are influenced by epigenetic marks, such as
      histone modification and DNA methylation, play a crucial role in modulating gene
      transcription. To understand the relationship between histone modifications and
      regulatory elements in breast cancer cells, we compared our chromatin
      immunoprecipitation sequencing (ChIP-Seq) histone modification patterns for
      histone H3K4me1, H3K4me3, H3K9/16ac, and H3K27me3 in MCF-7 cells with publicly
      available formaldehyde-assisted isolation of regulatory elements (FAIRE)-chip
      signals in human chromosomes 8, 11, and 12, identified by a method called FAIRE.
      Active regulatory elements defined by FAIRE were highly associated with active
      histone modifications, like H3K4me3 and H3K9/16ac, especially near transcription
      start sites. The H3K9/16ac-enriched genes that overlapped with FAIRE signals
      (FAIRE-H3K9/14ac) were moderately correlated with gene expression levels. We also
      identified functional sequence motifs at H3K4me1-enriched FAIRE sites upstream of
      putative promoters, suggesting that regulatory elements could be associated with
      H3K4me1 to be regarded as distal regulatory elements. Our results might provide
      an insight into epigenetic regulatory mechanisms explaining the association of
      histone modifications with open chromatin structure in breast cancer cells.

PMID- 23166526
TI  - Systems Biological Approaches Reveal Non-additive Responses and Multiple
      Crosstalk Mechanisms between TLR and GPCR Signaling.
AB  - A variety of ligands differ in their capacity to bind the receptor, elicit gene
      expression, and modulate physiological responses. Such receptors include Toll
      like receptors (TLRs), which recognize various patterns of pathogens and lead to
      primary innate immune activation against invaders, and G-protein coupled
      receptors (GPCRs), whose interaction with their cognate ligands activates
      heterotrimeric G proteins and regulates specific downstream effectors, including
      immuno-stimulating molecules. Once TLRs are activated, they lead to the
      expression of hundreds of genes together and bridge the arm of innate and
      adaptive immune responses. We characterized the gene expression profile of Toll
      like receptor 4 (TLR4) in RAW 264.7 cells when it bound with its ligand, 2-keto-3
      deoxyoctonate (KDO), the active part of lipopolysaccharide. In addition, to
      determine the network communications among the TLR, Janus kinase (JAK)/signal
      transducer and activator of transcription (STAT), and GPCR, we tested RAW 264.7
      cells with KDO, interferon-beta, or cAMP analog 8-Br. The ligands were also
      administered as a pair of double and triple combinations.

PMID- 23166527
TI  - Discovery and Evaluation of Polymorphisms in the AKT2 and AKT3 Promoter Regions
      for Risk of Korean Lung Cancer.
AB  - AKT is a signal transduction protein that plays a central role in the
      tumorigenesis. There are 3 mammalian isoforms of this serine/threonine protein
      kinase-AKT1, AKT2, and AKT3-showing a broad tissue distribution. We first
      discovered 2 novel polymorphisms (AKT2 -9826 C/G and AKT3 -811 A/G), and we
      confirmed 6 known polymorphisms (AKT2 -9473 C/T, AKT2 -9151 C/T, AKT2 -9025 C/T,
      AKT2 -8618G/A, AKT3 -675 A/-, and AKT3 -244 C/T) of the AKT2 and AKT3 promoter
      region in 24 blood samples of Korean lung cancer patients using direct
      sequencing. To evaluate the role of AKT2 and AKT3 polymorphisms in the risk of
      Korean lung cancer, genotypes of the AKT2 and AKT3 polymorphisms (AKT2 -9826 C/G,
      AKT2 -9473 C/T, AKT2 -9151 C/T, AKT2 -9025 C/T, AKT2 -8618G/A, and AKT3 -675 A/-)
      were determined in 360 lung cancer patients and 360 normal controls. Statistical
      analyses revealed that the genotypes and haplotypes in the AKT2 and AKT3 promoter
      regions were not significantly associated with the risk of lung cancer in the
      Korean population. These results suggest that polymorphisms of the AKT2 and AKT3
      promoter regions do not contribute to the genetic susceptibility to lung cancer
      in the Korean population.

PMID- 23166528
TI  - Prediction of Colorectal Cancer Risk Using a Genetic Risk Score: The Korean
      Cancer Prevention Study-II (KCPS-II).
AB  - Colorectal cancer (CRC) is among the leading causes of cancer deaths and can be
      caused by environmental factors as well as genetic factors. Therefore, we
      developed a prediction model of CRC using genetic risk scores (GRS) and evaluated
      the effects of conventional risk factors, including family history of CRC, in
      combination with GRS on the risk of CRC in Koreans. This study included 187 cases
      (men, 133; women, 54) and 976 controls (men, 554; women, 422). GRS were
      calculated with most significantly associated single-nucleotide polymorphism with
      CRC through a genomewide association study. The area under the curve (AUC)
      increased by 0.5% to 5.2% when either counted or weighted GRS was added to a
      prediction model consisting of age alone (AUC 0.687 for men, 0.598 for women) or
      age and family history of CRC (AUC 0.692 for men, 0.603 for women) for both men
      and women. Furthermore, the risk of CRC significantly increased for individuals
      with a family history of CRC in the highest quartile of GRS when compared to
      subjects without a family history of CRC in the lowest quartile of GRS (counted
      GRS odds ratio [OR], 47.9; 95% confidence interval [CI], 4.9 to 471.8 for men;
      OR, 22.3; 95% CI, 1.4 to 344.2 for women) (weighted GRS OR, 35.9; 95% CI, 5.9 to
      218.2 for men; OR, 18.1, 95% CI, 3.7 to 88.1 for women). Our findings suggest
      that in Koreans, especially in Korean men, GRS improve the prediction of CRC when
      considered in conjunction with age and family history of CRC.

PMID- 23166529
TI  - Association Study between Folate Pathway Gene Single Nucleotide Polymorphisms and
      Gastric Cancer in Koreans.
AB  - Gastric cancer is ranked as the most common cancer in Koreans. A recent molecular
      biological study about the folate pathway gene revealed the correlation with a
      couple of cancer types. In the folate pathway, several genes are involved,
      including methylenetetrahydrofolate reductase (MTHFR), methyltetrahydrofolate
      homocysteine methyltransferase reductase (MTRR), and methyltetrahydrofolate
      homocysteine methyltransferase (MTR). The MTHFR gene has been reported several
      times for the correlation with gastric cancer risk. However, the association of
      the MTRR or MTR gene has not been reported to date. In this study, we
      investigated the association between the single nucleotide polymorphisms (SNPs)
      of the MTHFR, MTRR, and MTR genes and the risk of gastric cancer in Koreans. To
      identify the genetic association with gastric cancer, we selected 17 SNPs sites
      in folate pathway-associated genes of MTHFR, MTR, and MTRR and tested in 1,261
      gastric cancer patients and 375 healthy controls. By genotype analysis,
      estimating odds ratios and 95% confidence intervals (CI), rs1801394 in the MTRR
      gene showed increased risk for gastric cacner, with statistical significance both
      in the codominant model (odds ratio [OR], 1.39; 95% CI, 1.04 to 1.85) and
      dominant model (OR, 1.34; 95% CI, 1.02 to 1.75). Especially, in the obese group
      (body mass index >= 25 kg/m(2)), the codominant (OR, 9.08; 95% CI, 1.01 to 94.59)
      and recessive model (OR, 3.72; 95% CI, 0.92 to 16.59) showed dramatically
      increased risk (p < 0.05). In conclusion, rs1801394 in the MTRR gene is
      associated with gastric cancer risk, and its functional significance need to be
      validated.

PMID- 23166530
TI  - Effect of Combining Multiple CNV Defining Algorithms on the Reliability of CNV
      Calls from SNP Genotyping Data.
AB  - In addition to single-nucleotide polymorphisms (SNP), copy number variation (CNV)
      is a major component of human genetic diversity. Among many whole-genome analysis
      platforms, SNP arrays have been commonly used for genomewide CNV discovery.
      Recently, a number of CNV defining algorithms from SNP genotyping data have been
      developed; however, due to the fundamental limitation of SNP genotyping data for
      the measurement of signal intensity, there are still concerns regarding the
      possibility of false discovery or low sensitivity for detecting CNVs. In this
      study, we aimed to verify the effect of combining multiple CNV calling algorithms
      and set up the most reliable pipeline for CNV calling with Affymetrix Genomewide
      SNP 5.0 data. For this purpose, we selected the 3 most commonly used algorithms
      for CNV segmentation from SNP genotyping data, PennCNV, QuantiSNP; and BirdSuite.
      After defining the CNV loci using the 3 different algorithms, we assessed how
      many of them overlapped with each other, and we also validated the CNVs by
      genomic quantitative PCR. Through this analysis, we proposed that for reliable
      CNV-based genomewide association study using SNP array data, CNV calls must be
      performed with at least 3 different algorithms and that the CNVs consistently
      called from more than 2 algorithms must be used for association analysis, because
      they are more reliable than the CNVs called from a single algorithm. Our result
      will be helpful to set up the CNV analysis protocols for Affymetrix Genomewide
      SNP 5.0 genotyping data.

PMID- 23166531
TI  - Comparison of SNP variation and distribution in indigenous ethiopian and korean
      cattle (hanwoo) populations.
AB  - Although a large number of single nucleotide polymorphisms (SNPs) have been
      identified from the bovine genome-sequencing project, few of these have been
      validated at large in Bos indicus breeds. We have genotyped 192 animals,
      representing 5 cattle populations of Ethiopia, with the Illumina Bovine 8K SNP
      BeadChip. These include 1 Sanga (Danakil), 3 zebu (Borana, Arsi and Ambo), and 1
      zebu * Sanga intermediate (Horro) breeds. The Hanwoo (Bos taurus) was included
      for comparison purposes. Analysis of 7,045 SNP markers revealed that the mean
      minor allele frequency (MAF) was 0.23, 0.22, 0.21, 0.21, 0.23, and 0.29 for Ambo,
      Arsi, Borana, Danakil, Horro, and Hanwoo, respectively. Significant differences
      of MAF were observed between the indigenous Ethiopian cattle populations and
      Hanwoo breed (p < 0.001). Across the Ethiopian cattle populations, a common
      variant MAF (>=0.10 and <=0.5) accounted for an overall estimated 73.79% of the
      7,045 SNPs. The Hanwoo displayed a higher proportion of common variant SNPs
      (90%). Investigation within Ethiopian cattle populations showed that on average,
      16.64% of the markers were monomorphic, but in the Hanwoo breed, only 6% of the
      markers were monomorphic. Across the sampled Ethiopian cattle populations, the
      mean observed and expected heterozygosities were 0.314 and 0.313, respectively.
      The level of SNP variation identified in this particular study highlights that
      these markers can be potentially used for genetic studies in African cattle
      breeds.

PMID- 23166532
TI  - DNA barcoding of fish, insects, and shellfish in Korea.
AB  - DNA barcoding has been widely used in species identification and biodiversity
      research. A short fragment of the mitochondrial cytochrome c oxidase subunit I
      (COI) sequence serves as a DNA bio-barcode. We collected DNA barcodes, based on
      COI sequences from 156 species (529 sequences) of fish, insects, and shellfish.
      We present results on phylogenetic relationships to assess biodiversity the in
      the Korean peninsula. Average GC% contents of the 68 fish species (46.9%), the 59
      shellfish species (38.0%), and the 29 insect species (33.2%) are reported. Using
      the Kimura 2 parameter in all possible pairwise comparisons, the average
      interspecific distances were compared with the average intraspecific distances in
      fish (3.22 vs. 0.41), insects (2.06 vs. 0.25), and shellfish (3.58 vs. 0.14). Our
      results confirm that distance-based DNA barcoding provides sufficient information
      to identify and delineate fish, insect, and shellfish species by means of all
      possible pairwise comparisons. These results also confirm that the development of
      an effective molecular barcode identification system is possible. All DNA barcode
      sequences collected from our study will be useful for the interpretation of
      species-level identification and community-level patterns in fish, insects, and
      shellfish in Korea, although at the species level, the rate of correct
      identification in a diversified environment might be low.

PMID- 23166533
TI  - Electric Field Controlled Self-Assembly of Hierarchically Ordered Membranes.
AB  - Self-assembly in the presence of external forces is an adaptive, directed
      organization of molecular components under nonequilibrium conditions. While
      forces may be generated as a result of spontaneous interactions among components
      of a system, intervention with external forces can significantly alter the final
      outcome of self-assembly. Superimposing these intrinsic and extrinsic forces
      provides greater degrees of freedom to control the structure and function of self
      assembling materials. In this work we investigate the role of electric fields
      during the dynamic self-assembly of a negatively charged polyelectrolyte and a
      positively charged peptide amphiphile in water leading to the formation of an
      ordered membrane. In the absence of electric fields, contact between the two
      solutions of oppositely charged molecules triggers the growth of closed membranes
      with vertically oriented fibrils that encapsulate the polyelectrolyte solution.
      This process of self-assembly is intrinsically driven by excess osmotic pressure
      of counterions, and the electric field is found to modify the kinetics of
      membrane formation, and also its morphology and properties. Depending on the
      strength and orientation of the field we observe a significant increase or
      decrease of up to nearly 100% in membrane thickness, as well as the controlled
      rotation of nanofiber growth direction by 90 degrees, resulting in a significant
      increase in mechanical stiffness. These results suggest the possibility of using
      electric fields to control structure in self-assembly processes involving
      diffusion of oppositely charged molecules.

PMID- 23166534
TI  - Hepatocellular carcinoma in pakistan: where do we stand?
AB  - CONTEXT: From the 1970s till the mid 1990s, hepatitis B was the most common
      etiological factor for hepatocellular carcinoma (HCC) in Pakistan. Afterwards, a
      shift in HCC etiology was observed with a steady rise in hepatitis C virus (HCV)
      related HCC cases. HCV-3a, which is the most prevalent genotype, is also most
      frequent in HCV related HCC. There was an increase in the proportion of non-B non
      C (NBNC) HCC cases as well, which might be attributed to an increase in non
      alcoholic fatty liver disease. EVIDENCE ACQUISITION: The age-standardized rate
      for HCC is 7.64/100 000 in males and 2.8/100 000 in females. Male to female ratio
      is 3.6:1. Usual age of presentation is in the fifth and sixth decade. Most
      patients present with advanced disease, as they are not in a regular surveillance
      program. This is more so for patients with NBNC chronic liver disease. As many
      sonologists in Pakistan are practicing without sufficient training to pick up
      early lesions, alpha-fetoprotein is still recommended to compliment ultrasound in
      the surveillance of HCC. RESULTS: Majority of HCC patients present with
      nonresectable disease. Interventions such as transarterial chemoembolization,
      radiofrequency ablation, resection and chemotherapy including sorafenib are
      available in selected centers. Pakistan appears to be in an area of intermediate
      endemicity for HCC. There is a need for population based epidemiological studies
      to estimate the exact disease burden. CONCLUSIONS: Measures to prevent the spread
      of hepatitis C and B can slow down the epidemic rise in the incidence of HCC in
      the coming decades. There is a need to implement a proper surveillance program to
      identify HCC cases at an early stage.

PMID- 23166535
TI  - Effects of antiviral therapy on the recurrence of hepatocellular carcinoma after
      curative resection or liver transplantation.
AB  - CONTEXT: Hepatocellular carcinoma (HCC) is a fatal disease. Chronic hepatitis B
      virus (HBV) and/or hepatitis C virus (HCV) infection is the major cause of HCC.
      High viral replication rate and related hepatic/systematic inflammation are the
      major risk factors in HCC recurrence after hepatectomy or liver transplantation.
      EVIDENCE ACQUISITION: Some of the carcinogenesis-related HBV mutations are also
      associated with poor prognosis for HCC patients. Antiviral therapy is an option
      for improving HCC prognosis after surgery. In case of HBV-associated HCC,
      treatment with interferon and nucleos(t)ide analogues (NAs), especially
      interferon, is effective in improving the prognosis. However, long-term use of
      NAs increases the possibility of developing drug-resistant viral mutations such
      as the HBV rtA181T/sW172 mutation, which increases the risk of HCC recurrence.
      RESULTS: In cases of HCV-associated HCC, standard interferon with or without
      ribavirin therapy is effective in improving the prognosis of HCV-associated HCC;
      however, some HCV mutations, such as the amino acid substitution M91L, are
      associated with treatment failure and a poor prognosis. Therapeutic efficacy
      needs to be confirmed using largescale, randomized, placebo-controlled clinical
      trials. CONCLUSIONS: Surveillance of viral mutations during antiviral treatment
      and a better understanding of the associations of HCC recurrence with viral load,
      inflammation-associated signaling, and environmental factors can aid the
      development of more effective strategies for the prevention of HCC recurrence
      after surgery.

PMID- 23166537
TI  - Alpha-1 Antitrypsin Deficiency PI*Z and PI*S Gene Frequency Distribution Using on
      Maps of the World by an Inverse Distance Weighting (IDW) Multivariate
      Interpolation Method.
AB  - . BACKGROUND: Currently, there is a remarkable lack of genetic epidemiological
      studies on alpha 1-antitrypsin (AAT) deficiency in about half of the 193
      countries of the World. This fact impedes the establishment of a true prevalence
      pattern of this deleterious hereditary disorder in extensive regions of human
      population.  2. OBJECTIVES: The aim of the present study was to generate detailed
      maps of the frequency distribution of the two most frequent AAT deficiency
      alleles (i.e., PI*S and PI*Z) in all areas of the World.  3. MATERIALS AND
      METHODS: Available data provided by epidemiological studies performed in 94 of
      193 countries worldwide was used to develop detailed maps of these two alleles,
      We employed an informatics mathematical approach, namely: the ArcMap [a component
      of ESRI's ArcGIS Geographical Information System (GIS), for Microsoft Windows],
      based on the inverse distance weighting (IDW) multivariate interpolation method,
      which creates new numerical points from known data, using a simple logarithm
      based in the distance existing between them  4. RESULTS: In this method, PI*S and
      PI*Z frequencies were represented by colored scales, where qualitative colors
      were converted into quantitative data, providing information on their
      distribution in all parts of the world. This approach not only confirmed our
      previous data, but also provided digital images of the remaining regions of all
      continents.  5. CONCLUSIONS: By using this approach, striking differences were
      found among regions, and unsuspected significant values of the PI*S and PI*Z
      alleles frequencies were obtained for several geographic regions where have not
      been studied yet. In fact, some of these regions might be considered as priority
      targets for further screening studies on AAT deficiency, in order to identify,
      and properly manage, individuals at risk for the diverse adverse health effects
      associated with AAT deficiency.

PMID- 23166538
TI  - Hepatitis B virus / human immunodeficiency virus co-infection and its
      hepatocarcinogenic potential in sub-saharan black africans.
AB  - CONTEXT: Since the introduction of highly active anti-retroviral regimen for
      human immunodeficiency virus-1 infection, a significant increase in the incidence
      of hepatocellular carcinoma has been reported in patients already chronically
      infected with hepatitis B virus and then given this form of regimen for their
      retroviral infection. EVIDENCE ACQUISITION: This phenomenon was initially
      attributed to the far more prolonged survival of those patients who received this
      new regimen, which provided sufficient time, allowing hepatitis B virus-induced
      hepatocellular carcinoma to develop. RESULTS: The current belief is that the
      increased incidence of hepatocellular carcinoma is because of co-infection with
      the two viruses, one known to be hepatocarcinogenic and the other suspected to
      increase the carcinogenic potential of the other. Because both hepatitis B virus
      and human immunodeficiency virus -1 are endemic in the Black population of sub
      Saharan Africa and are transmitted in similar ways, as many as 20% of this
      population are co-infected with the two viruses. In this way, the already high
      risk of Black African patients developing hepatitis B virus-induced
      hepatocellular carcinoma is further increased. CONCLUSIONS: The pathogenetic
      mechanism or mechanisms involved in the carcinogenic interaction between the
      hepatitis B virus and the human immunodeficiency virus-1 in sub-Saharan Black
      Africans and other populations co-infected with these viruses have yet to be
      determined.

PMID- 23166539
TI  - Respiratory review of 2012: pneumonia.
AB  - Pneumonia is the cause of significant morbidity and mortality, despite advances
      in diagnosis and antibacterial treatment. Pneumonia is often misdiagnosed and
      mistreated up until recently. Recent classification of pneumonia consists of
      community-acquired pneumonia, health care-associated pneumonia, hospital-acquired
      pneumonia, and ventilator-associated pneumonia. The etiology, risk factors, and
      treatment are different among them. This article briefly introduces new concepts
      and ideas in biomarkers, diagnosis, treatment, prognosis, and prevention of
      pneumonia during the past 2 years. One of the most frequent subjects of recent
      papers was those about pandemic H1N1 in 2009.

PMID- 23166540
TI  - Asian Dust Particles Induce TGF-beta(1) via Reactive Oxygen Species in Bronchial
      Epithelial Cells.
AB  - BACKGROUND: Asian dust storms can be transported across eastern Asia. In vitro,
      Asian dust particle-induced inflammation and enhancement of the allergic reaction
      have been observed. However, the fibrotic effects of Asian dust particles are not
      clear. Production of transforming growth factor beta(1) (TGF-beta(1)) and
      fibronectin were investigated in the bronchial epithelial cells after exposure to
      Asian dust particulate matter (AD-PM10). METHODS: During Asian dust storm
      periods, air samples were collected. The bronchial epithelial cells were exposed
      to AD-PM10 with and without the antioxidant, N-acetyl-L-cysteine (NAC). Then TGF
      beta(1) and fibronectin were detected by Western blotting. The reactive oxygen
      species (ROS) was detected by the measurement of dicholorodihydrofluorescin
      (DCF), using a FACScan, and visualized by a confocal microscopy. RESULTS: The
      expression of TGF-beta(1), fibronectin and ROS was high after being exposed to AD
      PM10, compared to the control. NAC attenuated both TGF-beta(1) and fibronectin
      expression in the AD-PM10-exposed the bronchial epithelial cells. CONCLUSION: AD
      PM10 may have fibrotic potential in the bronchial epithelial cells and the
      possible mechanism is AD-PM10-induced intracellular ROS.

PMID- 23166536
TI  - S100 proteins as diagnostic and prognostic markers in colorectal and
      hepatocellular carcinoma.
AB  - CONTEXT: Clinical and experimental studies have suggested a link between S100
      gene ex-pression and neoplastic disorders, however, the molecular mechanisms of
      this associa-tion are not well understood. The aim of this review was to conduct
      a comprehensive literature search in order to understand the possible underlying
      molecular mechanisms of this association. We also discuss their application as
      diagnostic and prognostic mark-ers in colorectal and hepatocellular carcinoma.
      EVIDENCE ACQUISITIONS: We searched Pubmed (NLM) and Web of Science (ISI Web of
      Knowledge). RESULTS: S100 genes display a complex expression pattern in
      colorectal and hepatocel- lular carcinoma. They are expressed in tumor and/or
      tumor stroma cells, and they exert both pro- and antitumorigenic actions. In view
      of this complexity, it becomes clear that S100 proteins might act as both friend
      and foe. The biological role of the S100 genes is predicted to depend on the
      relative contributions of the different cell types at specific stages of tumor
      progression. CONCLUSIONS: Further research is required in order to uncover the
      functional role of S100 genes in tumorigenesis. Answers to this issue are needed
      before we can more fully un-derstand the clinical relevance of S100 protein
      expression within epithelial tumors, with regard to their potential applicability
      as biomarkers for diagnosis and therapy decisions.

PMID- 23166541
TI  - The efficacy of immediate diet for reducing local adverse events of inhaled
      corticosteroid: a pilot study.
AB  - BACKGROUND: Local adverse events associated with inhaled corticosteroid use,
      including dysphonia, pharyngitis and oral candidiasis, can affect adherence for
      treatment. 'Mouth rinsing method' has been used for reducing local adverse
      events, but it cannot ensure complete prevention. The goal of this pilot study
      was to identify whether the 'immediate diet method' can reduce local adverse
      events in a limited number of patients. METHODS: The study was conducted in a
      total of 98 patients, who had been prescribed a medium-dose fluticasone
      propionate for the first time, from January to October in 2010. One training
      nurse had performed the education on how to use the inhaler, including the mouth
      rinsing method. And with follow-ups at one month intervals, any patient who
      experienced such adverse events were educated on the immediate diet method,
      having a meal within 5 minutes after using an inhaler and they were checked on
      any incurrence of adverse events with one month intervals for 2 months. RESULTS:
      The mean age of patients was 65.9 years old. The local adverse events had
      incurred from 18.4% of the study subjects. When performed the follow-up
      observation in 18 patients with local adverse events after education on the
      immediate diet method, 14 patients (77.8%) had shown symptomatic improvements.
      Three of 4 patients did not show any improvement, in spite of implementing the
      immediate diet method. The other 1 patient did not practice the immediate diet
      method properly. CONCLUSION: The immediate diet method may be useful in reducing
      the local adverse events, caused by the use of inhaled corticosteroid.

PMID- 23166542
TI  - The impact of implementing critical care team on open general intensive care
      unit.
AB  - BACKGROUND: There are a plethora of literatures showing that high-intensity
      intensive care unit (ICU) physician staffing is associated with reduced ICU
      mortality. However, it is not widely used in ICUs because of limited budgets and
      resources. We created a critical care team (CCT) to improve outcomes in an open
      general ICU and evaluated its effectiveness based on patients' outcomes. METHODS:
      We conducted this prospective, observational study in an open, general ICU
      setting, during a period ranging from March of 2009 to February of 2010. The CCT
      consisted of five teaching staffs. It provided rapid medical services within
      three hours after calls or consultation. RESULTS: We analyzed the data of 830
      patients (157 patients of the CCT group and 673 patients of the non-CCT one).
      Patients of the CCT group presented more serious conditions than those of the non
      CCT group (acute physiologic and chronic health evaluation II [APACHE II] 20.2
      vs. 15.8, p<0.001; sequential organ failure assessment [SOFA] 5.5 vs. 4.6,
      p=0.003). The CCT group also had significantly more patients on mechanical
      ventilation than those in the non-CCT group (45.9% vs. 23.9%, p<0.001). Success
      rate of weaning was significantly higher in the CCT group than that of the non
      CCT group (61.1% vs. 44.7%, p=0.021). On a multivariate logistic regression
      analysis, the increased ICU mortality was associated with the older age, non-CCT,
      higher APACHE II score, higher SOFA score and mechanical ventilation (p<0.05).
      CONCLUSION: Although the CCT did not provide full-time services in an open
      general ICU setting, it might be associated with a reduced ICU mortality. This is
      particularly the case with patients on mechanical ventilation.

PMID- 23166543
TI  - Analysis of patients with hemoptysis in a tertiary referral hospital.
AB  - BACKGROUND: This study attempted to investigate the main causes of hemoptysis,
      the type of examinations used for diagnosis, the treatment modalities and
      outcomes. METHODS: A retrospective study was conducted on the medical records of
      221 patients admitted to the Chonnam National University Hospital, between
      January 2005 and February 2010, with hemoptysis. RESULTS: Bronchiectasis (32.6%),
      active pulmonary tuberculosis (18.5%), fungus ball (10.8%), and lung cancer
      (5.9%) accounted for most causes of hemoptysis. Computed tomography scan was the
      most sensitive diagnostic test when employed alone, with positive yield of 93.2%.
      There were 161 cases of conservative treatment (72.9%), 42 cases of bronchial
      artery embolization (BAE) (19.0%), and 18 cases of surgery (8.1%). Regarding the
      amount of hemoptysis, 70 cases, out of 221 cases, were mild (31.5%), 36 cases
      moderate (16.2%), and 115 cases massive hemoptysis (52.0%). Most of the patients
      were treated conservatively, but if there was more bleeding present, BAE or
      surgery was more commonly performed than the conservative treatment (p<=0.0001).
      In the multivariate model, severe hemoptysis and lung cancer were independently
      associated with short-term recurrence. BAE was independently associated with long
      term recurrence, and lung cancer was associated with in-hospital mortality. The
      overall in-hospital mortality rate was 11.3%. CONCLUSION: Hemoptysis is a common
      symptom with a good prognosis in most cases. However, patients exhibiting massive
      bleeding or those with malignancy had a poorer prognosis. In-hospital mortality
      was strongly related to the cause, especially in lung cancer.

PMID- 23166544
TI  - A Case of Pulmonary MALT Lymphoma Arising from Lymphocytic Interstitial
      Pneumonitis.
AB  - Pulmonary mucosa-associated lymphoid tissue-derived (MALT) lymphoma is a rare
      disease. This disorder is considered to be a model of antigen-driven lymphoma,
      which is driven either by autoantigens or by chronic inflammatory conditions. Low
      grade B-cell MALT lymphoma may develop from a nonneoplastic pulmonary
      lymphoproliferative disorder, such as lymphocytic interstitial pneumonitis (LIP).
      A recent estimate predicts that less than 5% of LIP patients acquire malignant,
      low-grade, B-cell lymphoma. In Korea, there has been no previous report of
      malignant low-grade, B-cell lymphoma, acquired from LIP. Here, we present the
      case of a patient with LIP that developed into pulmonary MALT lymphoma, six years
      after diagnosis.

PMID- 23166545
TI  - Plastic bronchitis in an adult with asthma.
AB  - Plastic bronchitis is a rare disease characterized by marked airway obstruction,
      via the formation of large gelatinous or rigid airway cast. In Korea, there were
      a few case reports with plastic bronchitis not in adults, but in children. So we
      report a case of an adult who was diagnosed as plastic bronchitis with
      eosinophilic casts, with no history of atopic and cardiac disease.

PMID- 23166546
TI  - Year-in-Review of Lung Cancer.
AB  - In the last several years, we have made slow but steady progress in understanding
      molecular biology of lung cancer. This review is focused on advances in
      understanding the biology of lung cancer that have led to proof of concept
      studies on new therapeutic approaches. The three selected topics include
      genetics, epigenetics and non-coding RNA. This new information represents
      progress in the integration of molecular mechanisms that to identify more
      effective ways to target lung cancer.

PMID- 23166547
TI  - Clinical Utility of Two Interferon-gamma Release Assays on Pleural Fluid for the
      Diagnosis of Tuberculous Pleurisy.
AB  - BACKGROUND: The release of interferon-gamma (IFN-gamma) by T lymphocytes
      increases after rechallenge with Mycobacterium tuberculosis antigen, especially,
      at a localized site of tuberculosis (TB) infection. We aimed to compare the
      clincial efficacy of two commercial IFN-gamma release assays from pleural fluid
      for the diagnosis in tuberculous pleurisy. METHODS: We performed T-SPOT.TB and
      QuantiFERON-TB Gold tests simultaneously on pleural fluid and peripheral blood
      samples from patients with pleural effusion, in South Korea, an area with
      intermediate TB burden. RESULTS: Thirty-six patients were enrolled prospectively,
      and tuberculous pleurisy was found in 21 patients. Both the numbers of IFN-gamma
      secreting T cells and the concentration of IFN-gamma were greater in the pleural
      tuberculous group, comparing with the non-tuberculous group. Moreover, in the
      tuberculous group, there was a significant difference in IFN-gamma producing spot
      forming cells using the T-SPOT.TB method between pleural fluid and peripheral
      blood. The receiver operating characteristic (ROC) curve, was the greatest for
      pleural fluid T-SPOT.TB test, followed by peripheral blood T-SPOT.TB test,
      peripheral blood QuantiFERON-TB Gold test, and pleural fluid QuantiFERON-TB Gold
      test (area under the ROC curve of 0.956, 0.890, 0.743, and 0.721, respectively).
      The T-SPOT.TB assay produced less indeterminate results than did QuantiFERON-TB
      Gold assay in both pleural fluid and peripheral blood. CONCLUSION: These findings
      suggest that the pleural fluid T-SPOT.TB test could be the most useful test among
      the IFN-gamma release assays for diagnosing tuberculous pleurisy in an area with
      an intermediate prevalence of TB infection.

PMID- 23166548
TI  - The significance of sedation control in patients receiving mechanical
      ventilation.
AB  - BACKGROUND: Adequate assessment and control of sedation play crucial roles in the
      proper performance of mechanical ventilation. METHODS: A total of 30 patients
      with various pulmonary diseases were prospectively enrolled. The study population
      was randomized into two groups. The sedation assessment group (SAG) received
      active protocol-based control of sedation, and in the empiric control group
      (ECG), the sedation levels were empirically adjusted. Subsequently, daily
      interruption of sedation (DIS) was conducted in the SAG. RESULTS: In the SAG, the
      dose of midazolam was significantly reduced by control of sedation (day 1, 1.3+/
      0.5 ug/kg/min; day 2, 0.9+/-0.4 ug/kg/min; p<0.01), and was significantly lower
      than the ECG on day 2 (p<0.01). Likewise, on day 2, sedation levels were
      significantly lower in the SAG than in the ECG. Significant relationship was
      found between Ramsay sedation scale and Richmond agitation-sedation scale (RASS;
      r(s)=-0.57), Ramsay Sedation Scale and Bispectral Index (BIS; r(s)=0.77), and
      RASS and BIS (r(s)=-0.79). In 10 patients, who didn't require re-sedation after
      DIS, BIS showed the earliest and most significant changes among the sedation
      scales. Ventilatory parameters showed significant but less prominent changes, and
      hemodynamic parameters didn't show significant changes. No seriously adverse
      events ensued after the implementation of DIS. CONCLUSION: Active assessment and
      control of sedation significantly reduced the dosage of sedatives in patients
      receiving mechanical ventilation. DIS, conducted in limited cases, suggested its
      potential efficacy and tolerability.

PMID- 23166549
TI  - Clinical predictors of survival in idiopathic pulmonary fibrosis.
AB  - BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a progressive disease.
      Effective treatment is not currently available and the prognosis is poor. The aim
      of our study was to identify clinical predictors of survival in patients with
      IPF. METHODS: By using medical record database of a university hospital, we
      reviewed the records of patients who had been diagnosed as having IPF from
      January 1996 through December 2007. RESULTS: Among 89 patients considered as
      having interstitial lung disease (ILD) on computed tomography (CT) of the chest,
      22 were excluded because of the diagnosis of other ILDs or connective tissue
      disease, and finally, 67 met the criteria of IPF. The mean age at the diagnosis
      of IPF was 70 years (range, 41~87 years) and 43 (64%) were male. The mean
      survival time following the diagnosis of IPF was 40 months (range, 0~179 months).
      Among them, 28 cases were diagnosed as the progressive state of IPF on the follow
      up CT examination, and the mean duration between diagnosis of IPF and progression
      was 31 months. Multivariate analysis using Cox regression model revealed that
      body mass index (BMI) less than 18.5 kg/m(2) (p=0.030; hazard ratio [HR], 12.085;
      95% confidence interval [CI], 1.277~114.331) and CT progression before 36 months
      from the diagnosis of IPF (p=0.042; HR, 13.564; 95% CI, 1.101~167.166) were
      independently associated with mortality. CONCLUSION: Since low BMI at the
      diagnosis of IPF and progression on follow-up CT were associated with poor
      prognosis, IPF patients with low BMI and/or progression before 36 months
      following the diagnosis should be closely monitored.

PMID- 23166550
TI  - Clinical analysis of spontaneous pneumomediastinum.
AB  - BACKGROUND: Spontaneous pneumomediastinum is a rare and benign condition that
      generally occurs in young generations without any precipitating factor or
      underlying disease. The purpose of this study is to review our experience in
      dealing with this entity and detail a reasonable course of assessment and
      management. METHODS: From December 1999 to May 2012, 32 spontaneous
      pneumomediastinum patients were managed in our hospital. We retrospectively
      reviewed the result of management. RESULTS: Patients ranged in age from 10 to 38
      years, with the mean age of 18.3+/-5.6 years. Twenty-five patients were men and
      seven were women. Initial WBC count was 10,039+/-2,993/uL and thirty-one patients
      underwent computed tomography. Twenty-two patients underwent esophagography and
      results were shown to be normal. Twenty-five patients were admitted in the
      hospital and the mean duration of admission was 3.4+/-2.0 days. All patients were
      managed conservatively and discharged without any complications. CONCLUSION:
      Spontaneous pneumomediastinum is a benign condition combined with mild
      inflammatory signs and secondary causes must to excluded to avoid unfavorable
      outcomes and select proper management modality.

PMID- 23166551
TI  - Endobronchial schwannoma treated by rigid bronchoscopy with argon plasma
      coagulation.
AB  - Primary endobronchial schwannomas are extremely rare tumors that originate from
      Schwann cells. We report a case of primary endobronchial schwannoma. A 44-year
      old woman, without respiratory symptoms, was presented with a nodule in the left
      main bronchus on her chest computed tomography scan. The nodule was removed by a
      rigid bronchoscopy with argon plasma coagulation. Biopsy confirmed the diagnosis
      of schwannoma. There was no recurrence during her 4-month follow-up.

PMID- 23166552
TI  - A Case of Streptococcus suis Infection Causing Pneumonia with Empyema in Korea.
AB  - Streptococcus suis causes meningitis and sepsis in pigs, but human infection has
      increased over the past few years in those who are exposed to pigs or raw pork.
      Most cases have occurred in Southeast Asia, but only two cases have been reported
      in South Korea, presenting with arthritis and meningitis. Here, we report a rare
      case of S. suis infection, a 60-year-old sailor, who visited the emergency room
      presenting septicemia, pneumonia with empyema and meningitis, showed full
      recovery; however, neurologic sequale of severe cognitive dysfunction was present
      after the usage of antibiotics and percutaneous drainage. S. suis was isolated
      from blood and pleural fluid and the strain was susceptible to penicillin and
      vancomycin. Increased awareness of S. suis infection and prevention are
      warranted.

PMID- 23166553
TI  - Pulmonary cryptococcosis mimicking primary lung cancer with multiple lung
      metastases.
AB  - Cryptococcosis is an invasive fungal infection, which is more common in
      immunocompromised patients. However, pulmonary cryptococcosis can occur in
      immunocompetent patients and should be considered on a differential diagnosis for
      nodular or mass-like lesions in chest radiograph. Recently, we experienced a
      patient with pulmonary cryptococcosis, successfully treated with oral fluconazole
      therapy. A 74-year-old female patient was referred for an evaluation of abnormal
      images, a large consolidative mass with multiple nodular consolidations and small
      nodules that mimics primary lung cancer with multiple lung to lung metastases.
      Computed tomography-guided lung biopsy confirmed the diagnosis of pulmonary
      cryptococcosis. The follow-up image taken after 4 months with oral fluconazole
      treatment showed marked improvement.

PMID- 23166554
TI  - Respiratory review of 2012: bronchoscopic innovations and advances.
AB  - Recent advances in bronchoscopy have led to changes in clinical diagnostics and
      therapeutics in pulmonary medicine. In diagnostic bronchoscopy, there have also
      been new developments in endobronchial ultrasound technology which may be
      incorporated into clinical practice in the near future. Functional bronchoscopy,
      which evaluates information such as airway pressure, airflow, or gas exchange,
      suggests promising clinical advances in the near future. In therapeutic
      bronchoscopy, bronchoscopic volume reduction is a novel approach for the
      treatment of severe emphysema. In this review, seven recently published articles
      representing current advances in bronchoscopy are summarized and discussed.

PMID- 23166555
TI  - Effect of Chrysin on Gene Expression and Production of MUC5AC Mucin from Cultured
      Airway Epithelial Cells.
AB  - BACKGROUND: We investigated whether chrysin affected MUC5AC mucin production and
      gene expression induced by phorbol ester (phorbol 12-myristate 13-acetate, PMA)
      or epidermal growth factor (EGF) from human airway epithelial cells. METHODS:
      Confluent NCI-H292 cells were pretreated with varying concentrations of chrysin
      for 30 minutes, and were then stimulated with PMA and EGF for 24 hours,
      respectively. MUC5AC mucin gene expression and mucin protein production were
      measured by reverse transcription polymerase chain reaction and enzyme-linked
      immunosorbent assay. RESULTS: Concentrations of 10uM and 100uM chrysin were found
      to inhibit the production of MUC5AC mucin protein induced by PMA; A concentration
      of 100uM chrysin also inhibited the production of MUC5AC mucin protein induced by
      EGF; 100uM chrysin inhibited the expression of MUC5AC mucin gene induced by PMA
      or EGF. The cytotoxicity of chrysin was checked by lactate dehydrogenase assay,
      and there was no cytotoxic effect observed for chrysin. CONCLUSION: These results
      suggest that chrysin can inhibit mucin gene expression and the production of
      mucin protein by directly acting on airway epithelial cells.

PMID- 23166556
TI  - Urine Cotinine for Assessing Tobacco Smoke Exposure in Korean: Analysis of the
      Korea National Health and Nutrition Examination Survey (KNHANES).
AB  - BACKGROUND: The level of urine cotinine is an indicator of tobacco smoke
      exposure. The purpose of this study is to investigate urine cotinine for the
      purpose of assessing the smoking status of Korean smokers and non-smokers exposed
      to tobacco smoke. METHODS: The subjects were identified from the 2007-2009 and
      the 2010 data sets of the Korea National Health and Nutrition Examination Survey
      (KNHANES). They were assigned as non-smokers, current smokers and ex-smokers. Non
      smokers were also divided into three subset groups according to the duration of
      smoke exposure. Each group was stratified by gender prior to analysis. RESULTS:
      The median value of urine cotinine in the male current smokers was 1,221.93 ng/mL
      which was the highest among all groups. The difference between levels of urine
      cotinine for male and the female groups was statistically significant (p<0.01).
      In the female group, passive smoke exposure groups reported higher urine cotinine
      levels than non-exposure groups (p=0.01). The cutoff point for the discrimination
      of current smokers from non-smokers was 95.6 ng/mL in males and 96.8 ng/mL in
      females. The sensitivity and specificity were 95.2% and 97.1%, respectively, in
      males, 96.1% and 96.5% in females. However, the determination of urine cotinine
      level was not useful in distinguishing between passive smoke exposure groups and
      non-exposure groups. CONCLUSION: Urine cotinine concentration is a useful
      biomarker for discriminating non-smokers from current smokers. However, careful
      interpretation is necessary for assessing passive smoke exposure by urine
      cotinine concentration.

PMID- 23166557
TI  - Prevalence of Latent Tuberculosis Infection among Medical Students in South
      Korea.
AB  - BACKGROUND: We investigated the prevalence of latent tuberculosis infection
      (LTBI) among medical students in South Korea. METHODS: Students from one medical
      school, who were in second- or third-year classes before clerkship course, were
      enrolled for three consecutive years in the study. A standard questionnaire was
      given to each participant, and tuberculin skin test (TST), QuantiFERON-TB GOLD In
      Tube (QFT-GIT) assay, and chest radiography were performed. RESULTS: A total of
      153 participants were enrolled in the study. The mean age of the subjects was
      21.9+/-0.9 years, 105 (68.6%) were male, and 132 (86.3%) had been vaccinated with
      Bacille Calmette-Guerin (BCG). Four students (2.6%) had a history of contact with
      tuberculosis (TB) patients during medical practice. No abnormal chest radiograph
      findings were found for any of the subjects. Of the 153 subjects, 23 (15.0%)
      tested positive for the TST, and 8 (5.2%) tested positive for the QFT-GIT. The
      agreement between the two tests was determined to be 0.34 using kappa
      coefficients. Of the four students who had a history of contact with TB patients,
      only one subject tested positive for both tests, and the other three students
      tested negative for both tests. CONCLUSION: A low prevalence of LTBI was found
      among medical students before clerkship course in South Korea.

PMID- 23166558
TI  - Prognostic factors of patients requiring prolonged mechanical ventilation in a
      medical intensive care unit of Korea.
AB  - BACKGROUND: We evaluated the clinical outcomes and prognostic factors of patients
      requiring prolonged mechanical ventilation (PMV), defined as ventilator care for
      >=21 days, who were admitted to the medical intensive care unit (ICU) of a
      university hospital in Korea. METHODS: During the study period, a total of 2,644
      patients were admitted to the medical ICU, and 136 patients (5.1%) were enrolled
      between 2005 and 2010. RESULTS: The mean age of the patients was 61.3+/-14.5
      years, and 94 (69.1%) were male. The ICU and six-month cumulative mortality rates
      were 45.6 and 58.8%, respectively. There were 96 patients with tracheostomy
      placement after admission and their mean period from admission to the day of
      tracheostomy was 21.3+/-8.4 days. Sixty-three patients (46.3%) were successfully
      weaned from ventilator care. Of the ICU survivors (n=74), 34 patients (45.9%)
      were transferred to other hospitals (not university hospitals). Two variables
      (thrombocytopenia [hazard ratio (HR), 1.964; 95% confidence interval (CI),
      1.225~3.148; p=0.005] and the requirement for vasopressors [HR, 1.822; 95% CI,
      1.111~2.986; p=0.017] on day 21) were found to be independent factors of survival
      on based on the Cox proportional hazard model. CONCLUSION: We found that patients
      requiring PMV had high six-month cumulative mortality rates, and that two
      clinical variables (measured on day 21), thrombocytopenia and requirement for
      vasopressors, may be associated with prognostic indicators.

PMID- 23166559
TI  - A case of acute pulmonary thromboembolism after taking tadalafil.
AB  - Tadalafil is a phosphodiesterase-5 inhibitor (PDE5I), which is widely used to
      treat erectile dysfunction. Although PDE5Is have excellent safety profiles, and
      most of the side effects are mild, rare serious adverse events have been reported
      in association with PDE5Is. Thrombosis is one of those events, and a few previous
      reports have suggested the association of PDE5Is with thrombosis. We report the
      case of a 61-year-old male who developed pulmonary embolism combined with
      pulmonary infarction directly after taking tadalafil. Both the patient and the
      physician suspected tadalafil as the culprit drug, as the patient was in an
      otherwise healthy condition. However, after extensive evaluation, we noticed that
      factor VIII levels were elevated. Prior reports suggesting the association
      between thrombosis and PDEIs either lack complete information on coagulation
      factors, or show inconsistencies in their results. Physicians should operate
      caution prior to accepting the diagnosis of adverse drug reaction.

PMID- 23166560
TI  - A Case of Peritoneal Tuberculosis Developed after Infliximab Therapy for
      Refractory RA.
AB  - Recently, interferon gamma releasing assay has been recommended to compensate the
      tuberculin skin test (TST) for screening for latent tuberculosis infection
      (LTBI). Although it improved the detection of LTBI before treatment with tumor
      necrosis factor blocker, its application to immune suppressed patients is
      limited. We report a case of peritoneal tuberculosis (TB) developed in a patient
      who tested positive for TST and QuantiFERON-TB Gold (QFT-G) before infliximab
      therapy, to emphasize the importance of monitoring during treatment. A 52-year
      old woman presented with abdominal distension. She had been diagnosed with
      seropositive rheumatoid arthritis six years ago. She had started taking
      infliximab six months ago. All screening tests for TB were performed and the
      results of all were negative. At admission, the results of repeated TST and QFT-G
      tests were positive. Histopathological examination confirmed peritoneal TB. The
      patient started anti-TB therapy and the symptoms were relieved.

PMID- 23166561
TI  - NMR in the Analysis of Functional Chemokine Interactions and Drug Discovery.
AB  - The involvement of chemokines and chemokine receptors in a great variety of
      pathological indications underscores their utility as therapeutic targets. In
      general, chemokine-mediated migration and signaling requires three distinct
      interactions: self-association, glycosaminoglycan (GAG) binding, and activation
      of G protein-coupled receptors (GPCRs). Solution-state nuclear magnetic resonance
      (NMR) spectroscopy has long been used to determine the apo structure of
      chemokines and monitor complex formation; however, it has never contributed
      directly to drug discovery efforts that are traditionally focused on the
      previously inaccessible chemokine receptors. Our lab recently demonstrated that
      NMR structures can be successfully utilized to direct drug discovery against
      chemokines. The ease of collecting chemokine structural data coupled with the
      increased efficiency of structure-based drug discovery campaigns makes chemokine
      directed therapies particularly attractive. In addition, recent advances in
      sample preparation, spectrometer hardware, and pulse program development are
      allowing researchers to examine interactions with previously inaccessible
      partners - including full-length chemokine receptors. These developments will
      facilitate exploration of novel ways to modulate chemokine activity using
      structure-guided drug discovery.

PMID- 23166562
TI  - Assembly and Stability of alpha-Helical Membrane Proteins.
AB  - Grease to grease - this is how one might begin to describe the tendency of
      hydrophobic stretches in protein amino acid sequences to form transmembrane
      domains. While this simple rule contains a lot of truth, the mechanisms of
      membrane protein folding, the insertion of hydrophobic protein domains into the
      lipid bilayer, and the apparent existence of highly polar residues in some
      proteins in the hydrophobic membrane core are subjects of lively debate - an
      indication that many details remain unresolved. Here, we present a historical
      survey of recent insights from experiments and computational studies into the
      rules and mechanisms of alpha-helical membrane protein assembly and stability.

PMID- 23166563
TI  - Duloxetine in affective disorders: a naturalistic study on psychiatric and
      medical comorbidity, use in association and tolerability across different age
      groups.
AB  - OBJECTIVE: Duloxetine, a selective serotonin and norepinephrine reuptake
      inhibitor (SNRI), is currently approved in many countries for the treatment of
      Major Depressive Disorder (MDD) and Generalized Anxiety Disorder (GAD). The
      present naturalistic study was aimed to investigate tolerability of Duloxetine in
      a sample of patients with affective disorders and psychiatric/medical
      comorbidity, comparing tolerability in monotherapy versus polytherapy and across
      different age groups. METHODS: The sample included 165 patients, affected by
      anxiety and/or mood disorders with or without comorbidity, who had been taken
      Duloxetine for at least 1 month. Sample variables were collected through a
      retrospective chart review. RESULTS: Most common primary diagnoses were MDD (49.1
      %), Bipolar Disorder (BD) (15.7 %) and GAD (5.5%). The 40 % of the sample had
      psychiatric comorbidity: in particular, anxiety disorders (15.8 %) (GAD 7.9%,
      Panic Disorder -PD- 7.3%) and personality disorders (9.1%) as the most frequent
      ones. With respect to medical comorbidities (68% of the sample), hypertension
      (12.1%) and diabetes (7.3%) were the most common ones. Mean duration of treatment
      and dosage of Duloxetine were, respectively, 11 months (+/- 9.1) and 70 mg/day
      (+/- 28.6). The 68 % of the sample received Duloxetine in association with other
      drugs. Minor side-effects, in particular drowsiness and gastrointestinal
      problems, were reported by 15 % of the sample. No difference in terms of
      tolerability across distinct groups, divided on the basis of mono- vs polytherapy
      as well as of different age, was found. CONCLUSION: Duloxetine, mostly
      administered in patients with affective disorders with psychiatric/ medical
      comorbidity and in association with other drugs, appeared to be well tolerated,
      showing limited rates of side effects of mild intensity. Further naturalistic
      studies are warranted to confirm present results.

PMID- 23166564
TI  - Prevalence and correlates of mental distress among working adults in ethiopia.
AB  - OBJECTIVE: To evaluate the prevalence of mental distress and its correlates among
      working Ethiopian adults. METHODS: This cross-sectional study of 2,180
      individuals (1,316 men and 864 women) was conducted among working adults in Addis
      Ababa, Ethiopia. A structured questionnaire was used to collect information on
      socio-demographic and lifestyle characteristics of participants. Mental distress
      was assessed using the self-reporting questionnaire (SRQ). Logistic regression
      was employed to estimate adjusted odds ratios (OR) and 95% confidence intervals
      (95% CI). RESULTS: The prevalence of mental distress in the study sample was
      17.7% (25.9% in women and 12.4% in men). Younger participants (age <=24 years)
      had the highest prevalence of mental distress (35.5% in women and 16.7% in men).
      The odds of mental distress was 2.47-fold higher among women as compared with men
      (OR=2.47, 95% CI 1.97-3.09). Participants reporting excellent health status had a
      50% reduced odds of mental distress (OR=0.47; 95%CI: 0.38-0.59); and moderate
      alcohol consumption was associated with a slight increased odds of mental
      distress (OR=1.26; 95%CI: 1.00-1.67). CONCLUSION: A high prevalence of mental
      distress was observed among working adults in Ethiopia. Our findings suggest that
      the workforce institutions should provide targeted prevention and intervention
      programs to improve the mental health state of their employees. National mental
      health policy that clearly outlines and addresses mental distress among working
      adults is also warranted.

PMID- 23166565
TI  - Objective Measures of Behavior Manifestations in Adult ADHD and Differentiation
      from Participants with Bipolar II Disorder, Borderline Personality Disorder,
      Participants with Disconfirmed ADHD as Well as Normative Participants.
AB  - BACKGROUND: The present study evaluated two psychometric instruments derived from
      the objective measurement of adult ADHD using the Quantified Behavior Test Plus.
      The instruments were examined in ADHD versus a clinical group with overlapping
      symptoms including borderline personality disorder and bipolar II disorder, and
      another clinical group with participants assessed for but disconfirmed a
      diagnosis of ADHD as well as adult normative participants. METHODS: The
      Quantified Behavior Test Plus includes Continuous Performance Testing and a
      Motion Tracking System with parameters related to attention and activity
      operationalized as the cardinal symptoms of ADHD and then summarized into a
      Weighed Core Symptoms scale with ten cut-points ranging from 0 to 100. A
      categorical predictor variable called Prediction of ADHD was used to examine the
      levels of sensitivity and specificity for the Quantified Behavior Test Plus with
      regard to ADHD. RESULTS: The Weighed Core Symptoms scale separated ADHD and
      normative participants from each other as well as from the two clinical reference
      groups. The scale reported highest levels of core symptoms in the ADHD group and
      the lowest level of core symptoms in the normative group. Analyses with
      Prediction of ADHD yielded 85 % specificity for the normative group, 87 %
      sensitivity for the ADHD group, 36 % sensitivity for the bipolar II and
      borderline group and 41 % sensitivity for the group with a disconfirmed diagnosis
      of ADHD. CONCLUSIONS: The Weighed Core Symptoms scale facilitated objective
      assessment of adult ADHD insofar that the ADHD group presented more core symptoms
      than the other two clinical groups and the normative group. Sensitivity for the
      Quantified Behavior Test Plus was lower in complex clinical groups with Bipolar
      II disorder, Borderline disorder and in patients with a disconfirmed diagnosis of
      ADHD. The psychometric instruments may be further evaluated with regard to well
      documented and effective treatment programs for ADHD core symptoms.

PMID- 23166566
TI  - Control of risk factors for cardiovascular disease among adults with previously
      diagnosed type 2 diabetes mellitus: a descriptive study from a middle eastern
      arab population.
AB  - BACKGROUND: Despite the high burden of type 2 diabetes mellitus (T2DM) in Oman,
      there are scarce data from a nationally representative sample on the level of
      glycaemia and other cardiovascular (CVD) risk factor control. OBJECTIVE: To
      estimate the proportion of patients with T2DM at goal for glycaemia and CVD risk
      factors using the National Diabetes Guidelines (NDG) and the American Diabetes
      Association (ADA) clinical care guidelines; and to assess the quality of selected
      services provided to patients with T2DM. METHODS: A sample of 2,551 patients (47%
      men) aged >=20 years with T2DM treated at primary health care centers was
      selected. Patient characteristics, medical history and treatment were collected
      from case notes, Diabetes Registers and computer frameworks including the use of
      the last 3 laboratory investigations results and blood pressure (BP) readings
      recorded in 2007. RESULTS: The overall mean age of the cohort was 54+/-13 years
      with an average median duration of diabetes of 4 (range 2 to 6) years. Over 80%
      of patients were overweight or obese (body mass index (BMI) of >=25 Kg/m(2)).
      Sixty-nine percent were on oral anti-diabetic medication, 52% on anti
      hypertensives and 40% on lipid lowering drugs. Thirty percent of patients were at
      goal for glycosylated haemoglobin level (<7%), 26% for BP (systolic/diastolic
      <130/80 mmHg), 55% for total cholesterol (<5.2 mmol/l), 4.5% for low-density
      lipoprotein cholesterol (<1.8 mmol/l), 52% for high-density lipoprotein
      cholesterol (>1 mmol/l for men, >1.3 mmol/l for women), and 61% for triglycerides
      (<1.7 mmol/l). Over 37% had micro-albuminuria and 5% had diabetic nephropathy.
      CONCLUSION: Control of hyperglycaemia and other CVD risk factor appears to be
      suboptimal in Omani patients with T2DM and need to be addressed in the triad of
      patient, physician and health system.

PMID- 23166567
TI  - Biodegradation of Selected Nigerian Fruit Peels by the use of a Non-pathogenic
      Rhizobium species CWP G34B.
AB  - This study was carried out to determine the ability of Rhizobium species CWP G34B
      to degrade the peels of selected Nigerian fruits. The potential of the bacterium
      to digest some carbon sources (lactose, maltose, sucrose and mannitol) and peels
      of some Nigerian fruits (pineapple, orange, plantain, banana, pawpaw and mango
      fruits) was investigated by growing the organism on the substances separately
      after which DNSA reagent method was used to quantify glucose released into the
      medium. The results showed that the bacterium was able to degrade all the
      carbohydrates with the highest and the lowest glucose concentrations of 5.52
      mg/ml for lactose and 0.50 mg/ml for mannitol. The carbohydrate-catabolic-enzyme
      (CCE) activity ranged from 0.169 mg/ml to 1.346 mg/ml glucose per mg/ml protein.
      Mannitol exhibited the highest CCE activity while the lowest activity was
      observed in the presence of sucrose. The amount of extracellular protein
      synthesized was highest (9.803 mg/ml) in the presence of maltose and lowest
      (0.925 mg/ml) in mannitol. The mean polygalacturonase activity was 0.54 unit/ml
      when the bacterium was grown in pectin in contrast to 0.28 unit/ml when it was
      grown in mannitol. The bacterium showed ability to breakdown the peels of the
      Nigerian fruits with the highest capability in banana and pineapple (0.42 and
      0.41 mg/ml glucose per mg/ml protein respectively). The fruit-peel-degrading
      enzyme activity was lowest in orange peel (0.75 unit/ml).

PMID- 23166568
TI  - Mutants of Saccharomyces cerevisiae and Bacillus citri Changed the Protein
      Content of the Nigerian Oryza sativa variety "Igbimo" during Fermentation.
AB  - Effect of mutation on protein production by Saccharomyces cerevisiae and Bacillus
      citri, the best protein producing yeast and bacterium isolated during a previous
      natural fermentation of a Nigerian rice ("Igbimo"). The two microorganisms were
      grown to logarithmic phase and mutagenized separately using ethylmethyl
      sulphonate (EMS). The wild-types and variants were inoculated individually into
      sterile "Igbimo" rice. Fermentation was allowed to take place at 27 degrees C for
      7 days after which protein released into the rice was quantified using the Biuret
      reagent method. The data obtained showed that the mutants are different from each
      other. Some mutants did form the protein at lower concentrations, others at the
      same and higher concentrations than the mother strains. The parental strains of
      S. cerevisiae and B. citri synthesized 0.89 mg/mL and 0.36 mg/mL protein
      respectively. Four groups of the mutants are recognized: classes I, II, III and
      IV which are the Poor, Average, Good and Super Protein Producers with 0-0.20,
      0.21-0.50, 0.51-1.0 and 1.0 mg/mL protein respectively The yeast mutants produced
      higher amounts of protein than those of the bacterium.

PMID- 23166569
TI  - Expiratory Flow Limitation in Obstructive Sleep Apnea and COPD: A Quantitative
      Method to Detect Pattern Differences Using the Negative Expiratory Pressure
      Technique.
AB  - BACKGROUND: Expiratory flow limitation (EFL), determined by the negative
      expiratory pressure (NEP) technique, can exhibit overlapping patterns in COPD,
      obstructive sleep apnea (OSA) and non-OSA obesity. We assessed the ability of a
      quantitative method to assess EFL to discriminate COPD from obese and OSA
      patients during NEP (-2 to -3 cm H(2)O) testing. METHODS: EFL was quantified by
      measuring the area under the preceding control tidal breath (Vt) subtended by the
      NEP curve (%AUC). To quantify mean lost flow, the ratio of %AUC to percentage of
      control Vt over which EFL occurred (%EFL) (= %AUC/%EFL) was computed. Percent
      EFL, %AUC, and %AUC/%EFL was compared in 42 patients with COPD, 28 obese subjects
      without OSA, 50 with OSA (26 mild-moderate, 24 severe) and 19 control subjects,
      in seated and supine postures. RESULTS: All patients exhibited %EFL values
      significantly higher than control subjects, corrected for age and gender (ANOVA).
      All but the COPD group exhibited higher %EFL while supine, but not %AUC or
      %AUC/%EFL. Amongst seated subjects, %EFL was highest in COPD, and amongst supine
      groups, it was greatest in OSA and COPD. %AUC/%EFL was significantly higher in
      mild-moderate OSA than in COPD only while seated. %AUC or %AUC/%EFL did not
      discriminate amongst other cohorts in either posture. CONCLUSIONS: Computation of
      %EFL helps distinguish EFL in COPD, obese and OSA patients from those of control
      subjects. Computation of %AUC and %AUC/%EFL is useful in determining the
      magnitude of extrathoracic FL in individuals with obesity and OSA, but does not
      distinguish between cohorts.

PMID- 23166570
TI  - Extra-esophageal manifestations of gastroesophageal reflux disease: controversies
      between epidemiology and clicnic.
AB  - Gastroesophageal reflux disease (GERD) is widely associated with asthma, chronic
      cough, and laryngitis. Many studies have focused on acidic reflux; however, acid
      is just one of many factors that can cause pulmonary injury. The discrepancy
      between the high frequency of GERD in asthmatic patients and the ineffective
      reflux therapy outcomes in these patients suggests that GERD may cause injury
      through other mechanisms, such as pepsinogen, pepsin, bile salts, or other
      components of reflux materials, instead of the acid. Research using appropriate
      and innovative methodologies to investigate these potential inflammatory agents
      in patients with GERD is required to determine the underlying factors associated
      with pulmonary disorders in these patients.

PMID- 23166571
TI  - Nitric oxide metabolites as biomarkers for influenza-like acute respiratory
      infections presenting to the emergency room.
AB  - AIMS: Nitric oxide (NO) is increased in the respiratory tract in pulmonary
      infections. The aim was to determine whether nasal wash NO metabolites could
      serve as biomarkers of viral pathogen and disease severity in children with
      influenza-like illness (ILI) presenting to the emergency department (ED) during
      the 2009 influenza A H1N1 pandemic. METHODS: Children <=18 years old presenting
      to the ED with ILI were eligible. Nasal wash specimens were tested for NO
      metabolites, nitrate and nitrite, by HPLC and for respiratory viruses by real
      time PCR. RESULTS: Eighty-nine patients with ILI were prospectively enrolled
      during Oct-Dec, 2009. In the entire cohort, nasal wash nitrite was low to
      undetectable (interquartile range [IQR], 0 - 2 MUM), while median nitrate was 3.4
      MUM (IQR 0-8.6). Rhinovirus (23%), respiratory syncytial virus (RSV) (20%), novel
      H1N1 (19%), and adenovirus (11%) were the most common viruses found. Children
      with RSV subtype B-associated ILI had higher nitrate compared to all other
      viruses combined (P=0.002). CONCLUSION: Concentration of NO-derived nitrate in
      nasal secretions in children in the ED is suggestive of viral pathogen causative
      for ILI, and thus might be of clinical utility. Predictive potential of this
      putative biomarker for ILI needs further evaluation in sicker patients in a
      prospective manner.

PMID- 23166572
TI  - Septic arthritis due to Staphylococcus warneri: a diagnostic challenge.
AB  - A septic arthritis due to an indolent infection is a challenge for timely
      diagnosis. In recent years septic arthritides due to Staphylococcus Warneri are
      increasingly reported, mostly as a complication in patients with prosthetic
      devices. We report on a case of a 38 year old immunocompetent male with an
      indolent infection with this commensal of the skin after a stay at an intensive
      care unit and review the available literature. Tissue cultures obtained by
      arthroscopy might be helpful in obtaining a correct diagnosis.

PMID- 23166573
TI  - Determining bone bruises of the knee with magnetic resonance imaging.
AB  - INTRODUCTION: Injuries that develop secondary to minor traumas and cannot be
      detected via direct examination methods, but are detected via advanced imaging
      methods, such as magnetic resonance (MR) imaging, are called occult bone injuries
      or bone bruises. In such injuries, diagnostic arthroscopy usually does not reveal
      any pathology. MR imaging methods are quite beneficial for the diagnosis of such
      clinical conditions, which cause acute pain and restriction of motion. The
      present study aimed to assess occult bone injuries via MR imaging in patients who
      presented with minor knee trauma. PATIENTS AND METHODS: Twelve patients who
      presented with minor knee trauma were included in the study. Etiological factors
      in these patients included walking a long distance, falls, and minor trauma. All
      patients underwent physical examinations, direct radiological imaging, MR
      imaging, and diagnostic arthroscopy. RESULTS: Direct radiographs of the patients
      showed no pathological fracture. Bone marrow changes detected on the MR images
      were classified according to Lynch's classification as Type I lesions in nine
      patients and Type II lesions in three patients. CONCLUSION: We suggest that MR
      imaging methods should be the gold standard for the diagnosis of minor traumatic
      bruise injuries of the knee.

PMID- 23166574
TI  - Post-traumatic malunion of the proximal phalanx of the finger. Medium-term
      results in 24 cases treated by "in situ" osteotomy.
AB  - We report the clinical and radiographic medium-term results obtained for 20
      patients (24 fingers) treated surgically for post-traumatic malunion of the
      proximal phalanx of the finger. In all cases we performed a corrective
      osteoclasia or osteotomy at the site of malunion, followed by miniplate and screw
      fixation or by screw fixation only. The corrective osteoclasia was performed when
      malalignment was addressed within six weeks after injury. Two patients who had
      two fractures underwent additional surgery (tenolysis and/or capsulolysis) to
      improve function and ROM. At the final follow-up, at a mean of 24 months after
      corrective surgery, good or excellent clinical and radiographic results were
      obtained in all the patients. The pseudoclaw deformity disappeared in all cases
      in which a volar angulation deformity was present. An average improvement of
      about 30% in the range of motion of the MP and PIP joints was observed; only 4
      patients complained of mild pain at the maximum degrees of articular excursion of
      the MP and PIP joints. All the patients presented an improvement in grip
      strength. The mean DASH score in our series was 5 points. In two of the four
      cases treated by an intra-articular corrective osteotomy, mild radiographic signs
      of osteoarthritis at the MP joint were present. The data for this study confirm
      that "in situ" osteotomy stabilized by miniplates and/or screws is an effective
      procedure to correct post-traumatic malunions of the proximal phalanges of the
      fingers.

PMID- 23166575
TI  - Unilateral lumbosacral dislocation: case report and a comprehensive review.
AB  - Lumbosacral fracture-dislocation is a rare occurrence. There are more than 73
      cases reported in the English literature. We report on the imaging findings and
      surgical treatment in a patient suffered of unilateral traumatic L5-S1
      dislocation associated with severe disruption of the posterior ligamentous
      complex. The patient underwent open reduction and stabilization of L4-S1
      vertebrae with posterior instrumentation system. Open reduction and internal
      fixation was mandatory as post-traumatic ligamentous insufficiency would lead to
      abnormal motion. Operative treatment managed to produce a solid arthrodesis and
      restore stability of the lumbosacral junction. Follow-up revealed excellent
      results. This study reports a rare injury of the lumbosacral junction, and the
      literature concerning this unusual condition is extensively reviewed.

PMID- 23166576
TI  - Spinal fusion in the treatment of chronic low back pain: rationale for
      improvement.
AB  - Results following fusion for chronic low back pain (CLBP) are unpredictable and
      generally not very satisfying. The major reason is the absence of a detailed
      description of the symptoms of patients with pain, if present, in a motion
      segment of the spine. Various radiological findings have been attributed to
      discogenic pain, but if these radiological signs were really true signs of such
      pain, fusion would have been very successful. If discogenic pain exists, it
      should be possible to select these patients from all others within the CLBP
      population. Even if this selection were 100% perfect, however, identification of
      the painful segment would remain, and at present there is no reliable test for
      doing so. Regardless of whether an anterior or posterior type of fusion is
      performed, or even if artificial discs are used, solving the puzzle of pain
      associated with the presumed segmental disorder must be the primary goal.

PMID- 23166577
TI  - The special electrophysiological signs of inherited retinal dystrophies.
AB  - The study aim was to analyze the electrophysiological signs of inherited retinal
      dystrophies (IRD). Full-field and multifocal (mf) electroretinography (ERG) was
      analysed in three groups: 21 normal subjects, 21 randomly selected IRD patients,
      and 21 patients randomly selected from each of eleven IRD groups. As a result,
      median, 5-95 and 25-75 interquantile intervals of each full-field and mfERG
      parameter were estimated for each of the above mentioned groups and compared
      using a Kruskal-Wallis test. Quantitative and qualitative criteria defined in
      this study will improve the precision of differential diagnosis, the detection of
      IRD severity, and the efficacy of treatment. The quantitative and qualitative
      characteristics of ERG values, established in this study, can be further applied
      to the creation of software that will allow the automatic classification of the
      recording into a specific disease and degree of severity.

PMID- 23166578
TI  - Sphenoclival intraosseous lipoma in skull base.
AB  - Intraosseous lipoma is a rare benign tumor, mostly occurring in lower limb
      especially in os calcis and the metaphyses of long bones. Intraosseous lipoma of
      the skull is even rarer, with 12 cases having been reported to involve the
      sphenoid bone in the literature. We present the third reported case of
      sphenoclival intraosseous lipoma in a 43-year-old man with headache,
      hyperprolactinemia and visual disturbance. Performed Magnetic Resonance Imaging
      (MRI) revealed pituitary macroadenoma as well as a mildly expansile lesion with
      high signal intensity on both T1- and T2-weighted sequences within the left
      greater wing of the sphenoid and the clivus. The patient refused to undergo
      surgical removal of pituitary macroadenoma and medical treatment was initiated
      instead; thereafter, follow up Computed Tomography (CT) and MRI scans revealed
      regression of the pituitary macroadenoma whereas the sphenoclival lesion was
      depicted as a welldefined fat-containing intraosseous lesion which showed no
      perceptible growth, 17 months later.

PMID- 23166580
TI  - Is Age >= 70 Years an Important Predictor of Adverse Events Among Patients
      Enrolled in Metastatic Melanoma Trials? Findings from Pooled Analyses of
      Therapeutic Trials.
AB  - BACKGROUND: The current study was undertaken to explore whether older age
      predicts adverse event rates in metastatic melanoma patients participating in
      cancer clinical trials.  METHODS: Six phase II studies conducted at our
      institution for patients with metastatic disease were used in these pooled
      analyses: 1) ABT-510; 2) bortezomib, paclitaxel, and carboplatin; 3) everolimus;
      4) bevacizumab, paclitaxel, carboplatin; 5) carboplatin and abraxane; and 6)
      temozolomide and everolimus. In total, 233 patients, 64 elderly (>= 70 years) and
      169 younger, were analyzed for age-based differences in grade 2 or worse adverse
      events and other clinical outcomes.  RESULTS: Despite the fact that older
      patients had slightly worse performance scores, based on age, no differences in
      rates of adverse events were observed. Only worse baseline performance score
      predicted a higher rate of adverse events: patients with performance scores of
      one or worse were almost 4 times more likely to experience adverse events. Median
      cancer progression free survival and overall survival were comparable between
      older and younger patients.  CONCLUSION: These findings suggest that concern for
      adverse event rates should not preclude the enrollment of elderly melanoma
      patients to cancer clinical trials. Such patients should continue to be monitored
      carefully for tumor response and toxicity.

PMID- 23166579
TI  - Brain development in childhood.
AB  - Although human brain development continues throughout childhood and adolescence,
      it is a non-linear process both structurally and functionally. Here we review
      studies of brain development in healthy children from the viewpoint of structure
      and the perfusion of gray and white matter. Gray matter volume increases and then
      decreases with age, with the developmental time of the peak volume differing
      among brain regions in the first and second decades of life. On the other hand,
      white matter volume increase is mostly linear during those periods. As regards
      fractional anisotropy, most regions show an exponential trajectory with aging. In
      addition, cerebral blood flow and gray matter volume are proportional at similar
      developmental ages. Moreover, we show that several lifestyle choices, such as
      sleeping habits and breakfast staple, affect gray matter volume in healthy
      children. There are a number of uninvestigated important issues that require
      future study.

PMID- 23166581
TI  - Comparative analysis of the recently discovered hAT transposon TcBuster in human
      cells.
AB  - BACKGROUND: Transposons are useful tools for creating transgenic organisms,
      insertional mutagenesis, and genome engineering. TcBuster, a novel hAT-family
      transposon system derived from the red flour beetle Tribolium castaneum, was
      shown to be highly active in previous studies in insect embryoes.
      METHODOLOGY/PRINCIPAL FINDINGS: We tested TcBuster for its activity in human
      embryonic kidney 293 (HEK-293) cells. Excision footprints obtained from HEK-293
      cells contained small insertions and deletions consistent with a hAT-type repair
      mechanism of hairpin formation and non-homologous end-joining. Genome-wide
      analysis of 23,417 piggyBac, 30,303 Sleeping Beauty, and 27,985 TcBuster
      integrations in HEK-293 cells revealed a uniquely different integration pattern
      when compared to other transposon systems with regards to genomic elements.
      TcBuster experimental conditions were optimized to assay TcBuster activity in HEK
      293 cells by colony assay selection for a neomycin-containing transposon.
      Increasing transposon plasmid increased the number of colonies, whereas gene
      transfer activity dependent on codon-optimized transposase plasmid peaked at 100
      ng with decreased colonies at the highest doses of transposase DNA. Expression of
      the related human proteins Buster1, Buster3, and SCAND3 in HEK-293 cells did not
      result in genomic integration of the TcBuster transposon. TcBuster, Tol2, and
      piggyBac were compared directly at different ratios of transposon to transposase
      and found to be approximately comparable while having their own ratio
      preferences. CONCLUSIONS/SIGNIFICANCE: TcBuster was found to be highly active in
      mammalian HEK-293 cells and represents a promising tool for mammalian genome
      engineering.

PMID- 23166582
TI  - Which morphological characteristics are most influenced by the host matrix in
      downy mildews? A case study in Pseudoperonospora cubensis.
AB  - Before the advent of molecular phylogenetics, species concepts in the downy
      mildews, an economically important group of obligate biotrophic oomycete
      pathogens, have mostly been based upon host range and morphology. While molecular
      phylogenetic studies have confirmed a narrow host range for many downy mildew
      species, others, like Pseudoperonospora cubensis affect even different genera.
      Although often morphological differences were found for new, phylogenetically
      distinct species, uncertainty prevails regarding their host ranges, especially
      regarding related plants that have been reported as downy mildew hosts, but were
      not included in the phylogenetic studies. In these cases, the basis for deciding
      if the divergence in some morphological characters can be deemed sufficient for
      designation as separate species is uncertain, as observed morphological
      divergence could be due to different host matrices colonised. The broad host
      range of P. cubensis (ca. 60 host species) renders this pathogen an ideal model
      organism for the investigation of morphological variations in relation to the
      host matrix and to evaluate which characteristics are best indicators for
      conspecificity or distinctiveness. On the basis of twelve morphological
      characterisitcs and a set of twelve cucurbits from five different Cucurbitaceae
      tribes, including the two species, Cyclanthera pedata and Thladiantha dubia,
      hitherto not reported as hosts of P. cubensis, a significant influence of the
      host matrix on pathogen morphology was found. Given the high intraspecific
      variation of some characteristics, also their plasticity has to be taken into
      account. The implications for morphological species determination and the
      confidence limits of morphological characteristics are discussed. For species
      delimitations in Pseudoperonospora it is shown that the ratio of the height of
      the first ramification to the sporangiophore length, ratio of the longer to the
      shorter ultimate branchlet, and especially the length and width of sporangia, as
      well as, with some reservations, their ratio, are the most suitable
      characteristics for species delimitation.

PMID- 23166584
TI  - I1 imidazoline receptor: novel potential cytoprotective target of TVP1022, the S
      enantiomer of rasagiline.
AB  - TVP1022, the S-enantiomer of rasagiline (Azilect(r)) (N-propargyl-1R-aminoindan),
      exerts cyto/cardio-protective effects in a variety of experimental cardiac and
      neuronal models. Previous studies have demonstrated that the protective activity
      of TVP1022 and other propargyl derivatives involve the activation of p42/44
      mitogen-activated protein kinase (MAPK) signaling pathway. In the current study,
      we further investigated the molecular mechanism of action and signaling pathways
      of TVP1022 which may account for the cyto/cardio-protective efficacy of the drug.
      Using specific receptor binding and enzyme assays, we demonstrated that the
      imidazoline 1 and 2 binding sites (I(1) & I(2)) are potential targets for TVP1022
      (IC(50) =9.5E-08 M and IC(50) =1.4E-07 M, respectively). Western blotting
      analysis showed that TVP1022 (1-20 uM) dose-dependently increased the
      immunoreactivity of phosphorylated p42 and p44 MAPK in rat pheochromocytoma PC12
      cells and in neonatal rat ventricular myocytes (NRVM). This effect of TVP1022 was
      significantly attenuated by efaroxan, a selective I(1) imidazoline receptor
      antagonist. In addition, the cytoprotective effect of TVP1022 demonstrated in
      NRVM against serum deprivation-induced toxicity was markedly inhibited by
      efaroxan, thus suggesting the importance of I(1)imidazoline receptor in mediating
      the cardioprotective activity of the drug. Our findings suggest that the
      I(1)imidazoline receptor represents a novel site of action for the cyto/cardio
      protective efficacy of TVP1022.

PMID- 23166583
TI  - In vitro and ex vivo inhibition of human telomerase by anti-HIV nucleoside
      reverse transcriptase inhibitors (NRTIs) but not by non-NRTIs.
AB  - Telomerase is a specialized reverse transcriptase responsible for the de novo
      synthesis of telomeric DNA repeats. In addition to its established reverse
      transcriptase and terminal transferase activities, recent reports have revealed
      unexpected cellular activities of telomerase, including RNA-dependent RNA
      polymerization. This telomerase characteristic, distinct from other reverse
      transcriptases, indicates that clinically relevant reverse transcriptase
      inhibitors might have unexpected telomerase inhibition profiles. This is
      particularly important for the newer generation of RT inhibitors designed for
      anti-HIV therapy, which have reported higher safety margins than older agents.
      Using an in vitro primer extension assay, we tested the effects of clinically
      relevant HIV reverse transcriptase inhibitors on cellular telomerase activity. We
      observed that all commonly used nucleoside reverse transcriptase inhibitors
      (NRTIs), including zidovudine, stavudine, tenofovir, didanosine and abacavir,
      inhibit telomerase effectively in vitro. Truncated telomere synthesis was
      consistent with the expected mode of inhibition by all tested NRTIs. Through dose
      response experiments, we established relative inhibitory potencies of NRTIs on in
      vitro telomerase activity as compared to the inhibitory potencies of the
      corresponding dideoxynucleotide triphosphates. In contrast to NRTIs, the non
      nucleoside reverse transcriptase inhibitors (NNRTIs) nevirapine and efavirenz did
      not inhibit the primer extension activity of telomerase, even at millimolar
      concentrations. Long-term, continuous treatment of human HT29 cells with select
      NRTIs resulted in an accelerated loss of telomere repeats. All tested NRTIs
      exhibited the same rank order of inhibitory potencies on telomerase and HIV RT,
      which, according to published data, were orders-of-magnitude more sensitive than
      other DNA polymerases, including the susceptible mitochondria-specific DNA
      polymerase gamma. We concluded that telomerase activity could be inhibited by
      common NRTIs, including currently recommended RTI agents tenofovir and abacavir,
      which warrants large-scale clinical and epidemiological investigation of the off
      target effects of long-term highly active antiretroviral therapy (HAART) with
      these agents.

PMID- 23166585
TI  - Effect of synaptic transmission on viral fitness in HIV infection.
AB  - HIV can spread through its target cell population either via cell-free
      transmission, or by cell-to-cell transmission, presumably through virological
      synapses. Synaptic transmission entails the transfer of tens to hundreds of
      viruses per synapse, a fraction of which successfully integrate into the target
      cell genome. It is currently not understood how synaptic transmission affects
      viral fitness. Using a mathematical model, we investigate how different synaptic
      transmission strategies, defined by the number of viruses passed per synapse,
      influence the basic reproductive ratio of the virus, R(0), and virus load. In the
      most basic scenario, the model suggests that R(0) is maximized if a single virus
      particle is transferred per synapse. R(0) decreases and the infection eventually
      cannot be maintained for larger numbers of transferred viruses, because multiple
      infection of the same cell wastes viruses that could otherwise enter uninfected
      cells. To explain the relatively large number of HIV copies transferred per
      synapse, we consider additional biological assumptions under which an
      intermediate number of viruses transferred per synapse could maximize R(0). These
      include an increased burst size in multiply infected cells, the saturation of
      anti-viral factors upon infection of cells, and rate limiting steps during the
      process of synapse formation.

PMID- 23166586
TI  - Expression levels of the ABCG2 multidrug transporter in human erythrocytes
      correspond to pharmacologically relevant genetic variations.
AB  - We have developed a rapid, simple and reliable, antibody-based flow cytometry
      assay for the quantitative determination of membrane proteins in human
      erythrocytes. Our method reveals significant differences between the expression
      levels of the wild-type ABCG2 protein and the heterozygous Q141K polymorphic
      variant. Moreover, we find that nonsense mutations on one allele result in a 50%
      reduction in the erythrocyte expression of this protein. Since ABCG2
      polymorphisms are known to modify essential pharmacokinetic parameters, uric acid
      metabolism and cancer drug resistance, a direct determination of the erythrocyte
      membrane ABCG2 protein expression may provide valuable information for assessing
      these conditions or for devising drug treatments. Our findings suggest that
      erythrocyte membrane protein levels may reflect genotype-dependent tissue
      expression patterns. Extension of this methodology to other disease-related or
      pharmacologically important membrane proteins may yield new protein biomarkers
      for personalized diagnostics.

PMID- 23166587
TI  - Transcriptome sequencing and annotation for the Jamaican fruit bat (Artibeus
      jamaicensis).
AB  - The Jamaican fruit bat (Artibeus jamaicensis) is one of the most common bats in
      the tropical Americas. It is thought to be a potential reservoir host of Tacaribe
      virus, an arenavirus closely related to the South American hemorrhagic fever
      viruses. We performed transcriptome sequencing and annotation from lung, kidney
      and spleen tissues using 454 and Illumina platforms to develop this species as an
      animal model. More than 100,000 contigs were assembled, with 25,000 genes that
      were functionally annotated. Of the remaining unannotated contigs, 80% were found
      within bat genomes or transcriptomes. Annotated genes are involved in a broad
      range of activities ranging from cellular metabolism to genome regulation through
      ncRNAs. Reciprocal BLAST best hits yielded 8,785 sequences that are orthologous
      to mouse, rat, cattle, horse and human. Species tree analysis of sequences from
      2,378 loci was used to achieve 95% bootstrap support for the placement of bat as
      sister to the clade containing horse, dog, and cattle. Through substitution rate
      estimation between bat and human, 32 genes were identified with evidence for
      positive selection. We also identified 466 immune-related genes, which may be
      useful for studying Tacaribe virus infection of this species. The Jamaican fruit
      bat transcriptome dataset is a resource that should provide additional candidate
      markers for studying bat evolution and ecology, and tools for analysis of the
      host response and pathology of disease.

PMID- 23166588
TI  - HMGA1 reprograms somatic cells into pluripotent stem cells by inducing stem cell
      transcriptional networks.
AB  - BACKGROUND: Although recent studies have identified genes expressed in human
      embryonic stem cells (hESCs) that induce pluripotency, the molecular
      underpinnings of normal stem cell function remain poorly understood. The high
      mobility group A1 (HMGA1) gene is highly expressed in hESCs and poorly
      differentiated, stem-like cancers; however, its role in these settings has been
      unclear. METHODS/PRINCIPAL FINDINGS: We show that HMGA1 is highly expressed in
      fully reprogrammed iPSCs and hESCs, with intermediate levels in ECCs and low
      levels in fibroblasts. When hESCs are induced to differentiate, HMGA1 decreases
      and parallels that of other pluripotency factors. Conversely, forced expression
      of HMGA1 blocks differentiation of hESCs. We also discovered that HMGA1 enhances
      cellular reprogramming of somatic cells to iPSCs together with the Yamanaka
      factors (OCT4, SOX2, KLF4, cMYC - OSKM). HMGA1 increases the number and size of
      iPSC colonies compared to OSKM controls. Surprisingly, there was normal
      differentiation in vitro and benign teratoma formation in vivo of the HMGA1
      derived iPSCs. During the reprogramming process, HMGA1 induces the expression of
      pluripotency genes, including SOX2, LIN28, and cMYC, while knockdown of HMGA1 in
      hESCs results in the repression of these genes. Chromatin immunoprecipitation
      shows that HMGA1 binds to the promoters of these pluripotency genes in vivo. In
      addition, interfering with HMGA1 function using a short hairpin RNA or a dominant
      negative construct blocks cellular reprogramming to a pluripotent state.
      CONCLUSIONS: Our findings demonstrate for the first time that HMGA1 enhances
      cellular reprogramming from a somatic cell to a fully pluripotent stem cell.
      These findings identify a novel role for HMGA1 as a key regulator of the stem
      cell state by inducing transcriptional networks that drive pluripotency. Although
      further studies are needed, these HMGA1 pathways could be exploited in
      regenerative medicine or as novel therapeutic targets for poorly differentiated,
      stem-like cancers.

PMID- 23166589
TI  - Pregnancy is associated with decreased cardiac proteasome activity and oxidative
      stress in mice.
AB  - During pregnancy, the heart develops physiological hypertrophy. Proteasomal
      degradation has been shown to be altered in various models of pathological
      cardiac hypertrophy. Since the molecular signature of pregnancy-induced heart
      hypertrophy differs significantly from that of pathological heart hypertrophy, we
      investigated whether the cardiac proteasomal proteolytic pathway is affected by
      pregnancy in mice. We measured the proteasome activity, expression of proteasome
      subunits, ubiquitination levels and reactive oxygen production in the hearts of
      four groups of female mice: i) non pregnant (NP) at diestrus stage, ii) late
      pregnant (LP), iii) one day post-partum (PP1) and iv) 7 days post-partum (PP7).
      The activities of the 26 S proteasome subunits beta1 (caspase-like), and beta2
      (trypsin-like) were significantly decreased in LP (beta1?83.26 +/- 1.96%;
      beta2?74.74 +/- 1.7%, normalized to NP) whereas beta5 (chymotrypsin-like)
      activity was not altered by pregnancy but significantly decreased 1 day post
      partum. Interestingly, all three proteolytic activities of the proteasome were
      restored to normal levels 7 days post-partum. The decrease in proteasome activity
      in LP was not due to the surge of estrogen as estrogen treatment of
      ovariectomized mice did not alter the 26 S proteasome activity. The transcript
      and protein levels of RPN2 and RPT4 (subunits of 19 S), beta2 and alpha7
      (subunits of 20 S) as well as PA28alpha and beta5i (protein only) were not
      significantly different among the four groups. High resolution confocal
      microscopy revealed that nuclear localization of both core (20S) and RPT4 in LP
      is increased ~2-fold and is fully reversed in PP7. Pregnancy was also associated
      with decreased production of reactive oxygen species and ubiquitinated protein
      levels, while the de-ubiquitination activity was not altered by pregnancy or
      parturition. These results indicate that late pregnancy is associated with
      decreased ubiquitin-proteasome proteolytic activity and oxidative stress.

PMID- 23166590
TI  - Clinical presentation of atopic dermatitis by filaggrin gene mutation status
      during the first 7 years of life in a prospective cohort study.
AB  - BACKGROUND: Filaggrin null mutations result in impaired skin barrier functions,
      increase the risk of early onset atopic dermatitis and lead to a more severe and
      chronic disease. We aimed to characterize the clinical presentation and course of
      atopic dermatitis associated with filaggrin mutations within the first 7 years of
      life. METHOD: The COPSAC cohort is a prospective, clinical birth cohort study of
      411 children born to mothers with a history of asthma followed during their first
      7 years of life with scheduled visits every 6 months, as well as visits for acute
      exacerbations of dermatitis. Atopic dermatitis was defined in accordance with
      international guidelines and described at every visit using 35 predefined
      localizations and 10 different characteristics. RESULTS: A total of 170 (43%) of
      397 Caucasian children developed atopic dermatitis. The R501X and/or 2282del4
      filaggrin null mutations were present in 26 (15%) of children with atopic
      dermatitis and were primarily associated with predilection to exposed skin areas
      (especially the cheeks and back of the hands) and an up-regulation of both acute
      and chronic dermatitis. Furthermore, we found the filaggrin mutations to be
      associated with a higher number of unscheduled visits (3.6 vs. 2.7; p=0.04) and
      more severe (moderate-severe SCORAD 44% vs. 31%; p=0.14), and widespread
      dermatitis (10% vs. 6% of the body area, p<0.001) with an earlier age at onset
      (246 vs. 473 days, p<0.0001) compared to wild-type. CONCLUSION: In children,
      filaggrin mutations seem to define a specific endotype of atopic dermatitis
      primarily characterized by predilection to exposed areas of the body, in
      particular hands and cheeks, and an up-regulation in both acute and chronic
      morphological markers. Secondary, this endotype is characterized by an early
      onset of dermatitis and a more severe course, with more generalized dermatitis
      resulting in more frequent medical consultations.

PMID- 23166592
TI  - No longer confidential: estimating the confidence of individual regression
      predictions.
AB  - Quantitative predictions in computational life sciences are often based on
      regression models. The advent of machine learning has led to highly accurate
      regression models that have gained widespread acceptance. While there are
      statistical methods available to estimate the global performance of regression
      models on a test or training dataset, it is often not clear how well this
      performance transfers to other datasets or how reliable an individual prediction
      is-a fact that often reduces a user's trust into a computational method. In
      analogy to the concept of an experimental error, we sketch how estimators for
      individual prediction errors can be used to provide confidence intervals for
      individual predictions. Two novel statistical methods, named CONFINE and CONFIVE,
      can estimate the reliability of an individual prediction based on the local
      properties of nearby training data. The methods can be applied equally to linear
      and non-linear regression methods with very little computational overhead. We
      compare our confidence estimators with other existing confidence and
      applicability domain estimators on two biologically relevant problems (MHC
      peptide binding prediction and quantitative structure-activity relationship
      (QSAR)). Our results suggest that the proposed confidence estimators perform
      comparable to or better than previously proposed estimation methods. Given a
      sufficient amount of training data, the estimators exhibit error estimates of
      high quality. In addition, we observed that the quality of estimated confidence
      intervals is predictable. We discuss how confidence estimation is influenced by
      noise, the number of features, and the dataset size. Estimating the confidence in
      individual prediction in terms of error intervals represents an important step
      from plain, non-informative predictions towards transparent and interpretable
      predictions that will help to improve the acceptance of computational methods in
      the biological community.

PMID- 23166593
TI  - Localization of a female-specific marker on the chromosomes of the brown seaweed
      Saccharina japonica using fluorescence in situ hybridization.
AB  - BACKGROUND: There is a heteromorphic alternative life in the brown seaweed,
      Saccharina japonica (Aresch.) C. E. Lane, C. Mayes et G. W. Saunders ( =
      Laminaria japonica Aresch.), with macroscopic monoecious sporophytes and
      microscopic diecious gametophytes. Female gametophytes are genetically different
      from males. It is very difficult to identify the parent of a sporophyte using
      only routine cytological techniques due to homomorphic chromosomes. A sex
      specific marker is one of the best ways to make this determination.
      METHODOLOGY/PRINCIPAL FINDINGS: To obtain clear images, chromosome preparation
      was improved using maceration enzymes and fluorochrome 4', 6-diamidino-2
      phenylindole (DAPI). The chromosome number of both male and female haploid
      gametophytes was 31, and there were 62 chromosomes in diploid sporophytes.
      Although the female chromosomes ranged from 0.77 um to 2.61 um in size and were
      larger than the corresponding ones in the males (from 0.57 um to 2.16 um), there
      was not a very large X chromosome in the females. Based on the known female
      related FRML-494 marker, co-electrophoresis and Southern blot profiles
      demonstrated that it was inheritable and specific to female gametophytes. Using
      modified fluorescence in situ hybridization (FISH), this marker could be
      localized on one unique chromosome of the female gametophytes as well as the
      sporophytes, whereas no hybridization signal was detected in the male
      gametophytes. CONCLUSIONS/SIGNIFICANCE: Our data suggest that this marker was a
      female chromosome-specific DNA sequence. This is the first report of molecular
      marker localization on algal chromosomes. This research provides evidence for the
      benefit of using FISH for identifying molecular markers for sex identification,
      isolation of specific genes linked to this marker in the females, and sex
      determination of S. japonica gametophytes in the future.

PMID- 23166595
TI  - Prevention of Parent to Child Transmission (PPTCT) program data in India: an
      emerging data set for appraising the HIV epidemic.
AB  - BACKGROUND: Evidence based resource allocation and decentralized planning of an
      effective HIV/AIDS response requires reliable information on levels and trends of
      HIV at national and sub-national geographic levels. HIV sentinel surveillance
      data from antenatal clinics (HSS-ANC) has been an important data source to assess
      the HIV/AIDS epidemic in India, but has a number of limitations. We assess the
      value of Prevention of Parent to Child Transmission (PPTCT) programme data to
      appraise the HIV epidemic in India. METHODS/FINDINGS: HIV data from PPTCT sites
      were compared to HSS-ANC and general population level surveys at various
      geographic levels in the states of Karnataka, Maharashtra and Andhra Pradesh. Chi
      square tests were used to ascertain statistical significance. PPTCT HIV
      prevalence was significantly lower than HSS-ANC HIV prevalence (0.92% vs. 1.22%
      in Andhra Pradesh, 0.65% vs. 0.89% in Karnataka, 0.52% vs. 0.60% in Maharashtra,
      p<0.001 for all three states). In all three states, HIV prevalence from PPTCT
      centres that were part of the sentinel surveillance was comparable to HSS-ANC
      prevalence but significantly higher than PPTCT centres that were not part of the
      sentinel surveillance. HIV prevalence from PPTCT data was comparable to that from
      general population surveys. In all three states, significant declines in HIV
      prevalence between 2007 and 2010 were observed with the PPTCT data set. District
      level analyses of HIV trends and sub-district level analysis of HIV prevalence
      were possible using the PPTCT and not the HSS-ANC data sets. CONCLUSION: HIV
      prevalence from PPTCT may be a better proxy for general population prevalence
      than HSS-ANC. PPTCT data allow for analysis of HIV prevalence and trends at
      smaller geographic units, which is important for decentralized planning of
      HIV/AIDS programming. With further improvements to the system, India could
      replace its HSS-ANC with PPTCT programme data for surveillance.

PMID- 23166591
TI  - Nucleolar protein trafficking in response to HIV-1 Tat: rewiring the nucleolus.
AB  - The trans-activator Tat protein is a viral regulatory protein essential for HIV-1
      replication. Tat trafficks to the nucleoplasm and the nucleolus. The nucleolus, a
      highly dynamic and structured membrane-less sub-nuclear compartment, is the site
      of rRNA and ribosome biogenesis and is involved in numerous cellular functions
      including transcriptional regulation, cell cycle control and viral infection.
      Importantly, transient nucleolar trafficking of both Tat and HIV-1 viral
      transcripts are critical in HIV-1 replication, however, the role(s) of the
      nucleolus in HIV-1 replication remains unclear. To better understand how the
      interaction of Tat with the nucleolar machinery contributes to HIV-1
      pathogenesis, we investigated the quantitative changes in the composition of the
      nucleolar proteome of Jurkat T-cells stably expressing HIV-1 Tat fused to a TAP
      tag. Using an organellar proteomic approach based on mass spectrometry, coupled
      with Stable Isotope Labelling in Cell culture (SILAC), we quantified 520
      proteins, including 49 proteins showing significant changes in abundance in
      Jurkat T-cell nucleolus upon Tat expression. Numerous proteins exhibiting a fold
      change were well characterised Tat interactors and/or known to be critical for
      HIV-1 replication. This suggests that the spatial control and subcellular
      compartimentaliation of these cellular cofactors by Tat provide an additional
      layer of control for regulating cellular machinery involved in HIV-1
      pathogenesis. Pathway analysis and network reconstruction revealed that Tat
      expression specifically resulted in the nucleolar enrichment of proteins
      collectively participating in ribosomal biogenesis, protein homeostasis,
      metabolic pathways including glycolytic, pentose phosphate, nucleotides and amino
      acids biosynthetic pathways, stress response, T-cell signaling pathways and
      genome integrity. We present here the first differential profiling of the
      nucleolar proteome of T-cells expressing HIV-1 Tat. We discuss how these proteins
      collectively participate in interconnected networks converging to adapt the
      nucleolus dynamic activities, which favor host biosynthetic activities and may
      contribute to create a cellular environment supporting robust HIV-1 production.

PMID- 23166594
TI  - RNA splicing is responsive to MBNL1 dose.
AB  - Myotonic dystrophy (DM1) is a highly variable, multi-system disorder resulting
      from the expansion of an untranslated CTG tract in DMPK. In DM1 expanded CUG
      repeat RNAs form hairpin secondary structures that bind and aberrantly sequester
      the RNA splice regulator, MBNL1. RNA splice defects resulting as a consequence of
      MBNL1 depletion have been shown to play a key role in the development of DM1
      pathology. In patient populations, both the number and severity of DM1 symptoms
      increase broadly as a function of CTG tract length. However significant
      variability in the DM1 phenotype is observed in patients encoding similar CTG
      repeat numbers. Here we demonstrate that a gradual decrease in MBNL1 levels
      results both in the expansion of the repertoire of splice defects and an increase
      in the severity of the splice alterations. Thus, MBNL1 loss does not have an all
      or none outcome but rather shows a graded effect on the number and severity of
      the ensuing splice defects. Our results suggest that once a critical threshold is
      reached, relatively small dose variations of free MBNL1 levels, which may reflect
      modest changes in the size of the CUG tract or the extent of hairpin secondary
      structure formation, can significantly alter the number and severity of splice
      abnormalities and thus contribute to the phenotype variability observed in DM1
      patients.

PMID- 23166596
TI  - High tolerance to salinity and herbivory stresses may explain the expansion of
      Ipomoea cairica to salt marshes.
AB  - BACKGROUND: Invasive plants are often confronted with heterogeneous environments
      and various stress factors during their secondary phase of invasion into more
      stressful habitats. A high tolerance to stress factors may allow exotics to
      successfully invade stressful environments. Ipomoea cairica, a vigorous invader
      in South China, has recently been expanding into salt marshes.
      METHODOLOGY/PRINCIPAL FINDINGS: To examine why this liana species is able to
      invade a stressful saline environment, we utilized I. cairica and 3 non-invasive
      species for a greenhouse experiment. The plants were subjected to three levels of
      salinity (i.e., watered with 0, 4 and 8 g L(-1) NaCl solutions) and simulated
      herbivory (0, 25 and 50% of the leaf area excised) treatments. The relative
      growth rate (RGR) of I. cairica was significantly higher than the RGR of non
      invasive species under both stress treatments. The growth performance of I.
      cairica was not significantly affected by either stress factor, while that of the
      non-invasive species was significantly inhibited. The leaf condensed tannin
      content was generally lower in I. cairica than in the non-invasive I. triloba and
      Paederia foetida. Ipomoea cairica exhibited a relatively low resistance to
      herbivory, however, its tolerance to stress factors was significantly higher than
      either of the non-invasive species. CONCLUSIONS/SIGNIFICANCE: This is the first
      study examining the expansion of I. cairica to salt marshes in its introduced
      range. Our results suggest that the high tolerance of I. cairica to key stress
      factors (e.g., salinity and herbivory) contributes to its invasion into salt
      marshes. For I. cairica, a trade-off in resource reallocation may allow increased
      resources to be allocated to tolerance and growth. This may contribute to a
      secondary invasion into stressful habitats. Finally, we suggest that I. cairica
      could spread further and successfully occupy salt marshes, and countermeasures
      based on herbivory could be ineffective for controlling this invasion.

PMID- 23166597
TI  - Selective histonedeacetylase inhibitor M344 intervenes in HIV-1 latency through
      increasing histone acetylation and activation of NF-kappaB.
AB  - BACKGROUND: Histone deacetylase (HDAC) inhibitors present an exciting new
      approach to activate HIV production from latently infected cells to potentially
      enhance elimination of these cells and achieve a cure. M344, a novel HDAC
      inhibitor, shows robust activity in a variety of cancer cells and relatively low
      toxicity compared to trichostatin A (TSA). However, little is known about the
      effects and action mechanism of M344 in inducing HIV expression in latently
      infected cells. METHODOLOGY/PRINCIPAL FINDINGS: Using the Jurkat T cell model of
      HIV latency, we demonstrate that M344 effectively reactivates HIV-1 gene
      expression in latently infected cells. Moreover, M344-mediated activation of the
      latent HIV LTR can be strongly inhibited by a NF-kappaB inhibitor aspirin. We
      further show that M344 acts by increasing the acetylation of histone H3 and
      histone H4 at the nucleosome 1 (nuc-1) site of the HIV-1 long terminal repeat
      (LTR) and by inducing NF-kappaB p65 nuclear translocation and direct RelA DNA
      binding at the nuc-1 region of the HIV-1 LTR. We also found that M344 synergized
      with prostratin to activate the HIV-1 LTR promoter in latently infected cells.
      CONCLUSIONS/SIGNIFICANCE: These results suggest the potential of M344 in anti
      latency therapies and an important role for histone modifications and NF-kappaB
      transcription factors in regulating HIV-1 LTR gene expression.

PMID- 23166599
TI  - From schooling to shoaling: patterns of collective motion in zebrafish (Danio
      rerio).
AB  - Animal groups on the move can take different configurations. For example, groups
      of fish can either be 'shoals' or 'schools': shoals are simply aggregations of
      individuals; schools are shoals exhibiting polarized, synchronized motion. Here
      we demonstrate that polarization distributions of groups of zebrafish (Danio
      rerio) are bimodal, showing two distinct modes of collective motion corresponding
      to the definitions of shoaling and schooling. Other features of the group's
      motion also vary consistently between the two modes: zebrafish schools are faster
      and less dense than zebrafish shoals. Habituation to an environment can also
      alter the proportion of time zebrafish groups spend schooling or shoaling. Models
      of collective motion suggest that the degree and stability of group polarization
      increases with the group's density. Examining zebrafish groups of different sizes
      from 5 to 50, we show that larger groups are less polarized than smaller groups.
      Decreased fearfulness in larger groups may function similarly to habituation,
      causing them to spend more time shoaling than schooling, contrary to most models'
      predictions.

PMID- 23166598
TI  - Deep sequencing reveals differences in the transcriptional landscapes of fibers
      from two cultivated species of cotton.
AB  - Cotton (Gossypium) fiber is the most prevalent natural product used in the
      textile industry. The two major cultivated species, G. hirsutum (Gh) and G.
      barbadense (Gb), are allotetraploids with contrasting fiber quality properties.
      To better understand the molecular basis for their fiber differences, EST
      pyrosequencing was used to document the fiber transcriptomes at two key
      development stages, 10 days post anthesis (dpa), representing the peak of fiber
      elongation, and 22 dpa, representing the transition to secondary cell wall
      synthesis. The 617,000 high quality reads (89% of the total 692,000 reads) from 4
      libraries were assembled into 46,072 unigenes, comprising 38,297 contigs and
      7,775 singletons. Functional annotation of the unigenes together with comparative
      digital gene expression (DGE) revealed a diverse set of functions and processes
      that were partly linked to specific fiber stages. Globally, 2,770 contigs (7%)
      showed differential expression (>2-fold) between 10 and 22 dpa (irrespective of
      genotype), with 70% more highly expressed at 10 dpa, while 2,248 (6%) were
      differentially expressed between the genotypes (irrespective of stage). The most
      significant genes with differential DGE at 10 dpa included expansins and lipid
      transfer proteins (higher in Gb), while at 22 dpa tubulins, cellulose, and
      sucrose synthases showed higher expression in Gb. DGE was compared with
      expression data of 10 dpa-old fibers from Affymetrix microarrays. Among 543
      contigs showing differential expression on both platforms, 74% were consistent in
      being either over-expressed in Gh (242 genes) or in Gb (161 genes). Furthermore,
      the unigene set served to identify 339 new SSRs and close to 21,000 inter
      genotypic SNPs. Subsets of 88 SSRs and 48 SNPs were validated through mapping and
      added 65 new loci to a RIL genetic map. The new set of fiber ESTs and the gene
      based markers complement existing available resources useful in basic and applied
      research for crop improvement in cotton.

PMID- 23166600
TI  - Influence of opinion dynamics on the evolution of games.
AB  - Under certain circumstances such as lack of information or bounded rationality,
      human players can take decisions on which strategy to choose in a game on the
      basis of simple opinions. These opinions can be modified after each round by
      observing own or others payoff results but can be also modified after
      interchanging impressions with other players. In this way, the update of the
      strategies can become a question that goes beyond simple evolutionary rules based
      on fitness and become a social issue. In this work, we explore this scenario by
      coupling a game with an opinion dynamics model. The opinion is represented by a
      continuous variable that corresponds to the certainty of the agents respect to
      which strategy is best. The opinions transform into actions by making the
      selection of an strategy a stochastic event with a probability regulated by the
      opinion. A certain regard for the previous round payoff is included but the main
      update rules of the opinion are given by a model inspired in social interchanges.
      We find that the fixed points of the dynamics of the coupled model are different
      from those of the evolutionary game or the opinion models alone. Furthermore, new
      features emerge such as the independence of the fraction of cooperators with
      respect to the topology of the social interaction network or the presence of a
      small fraction of extremist players.

PMID- 23166601
TI  - Piecewise polynomial representations of genomic tracks.
AB  - Genomic data from micro-array and sequencing projects consist of associations of
      measured values to chromosomal coordinates. These associations can be thought of
      as functions in one dimension and can thus be stored, analyzed, and interpreted
      as piecewise-polynomial curves. We present a general framework for building
      piecewise polynomial representations of genome-scale signals and illustrate some
      of its applications via examples. We show that piecewise constant segmentation, a
      typical step in copy-number analyses, can be carried out within this framework
      for both array and (DNA) sequencing data offering advantages over existing
      methods in each case. Higher-order polynomial curves can be used, for example, to
      detect trends and/or discontinuities in transcription levels from RNA-seq data.
      We give a concrete application of piecewise linear functions to diagnose and
      quantify alignment quality at exon borders (splice sites). Our software (source
      and object code) for building piecewise polynomial models is available at
      http://sourceforge.net/projects/locsmoc/.

PMID- 23166602
TI  - The nonantibiotic small molecule cyslabdan enhances the potency of beta-lactams
      against MRSA by inhibiting pentaglycine interpeptide bridge synthesis.
AB  - The nonantibiotic small molecule cyslabdan, a labdan-type diterpene produced by
      Streptomyces sp. K04-0144, markedly potentiated the activity of the beta-lactam
      drug imipenem against methicillin-resistant Staphylococcus aureus (MRSA). To
      study the mechanism of action of cyslabdan, the proteins that bind to cyslabdan
      were investigated in an MRSA lysate, which led to the identification of FemA,
      which is involved in the synthesis of the pentaglycine interpeptide bridge of the
      peptidoglycan of MRSA. Furthermore, binding assay of cyslabdan to FemB and FemX
      with the function similar to FemA revealed that cyslabdan had an affinity for
      FemB but not FemX. In an enzyme-based assay, cyslabdan inhibited FemA activity,
      where as did not affected FemX and FemB activities. Nonglycyl and monoglycyl
      murein monomers were accumulated by cyslabdan in the peptidoglycan of MRSA cell
      walls. These findings indicated that cyslabdan primarily inhibits FemA, thereby
      suppressing pentaglycine interpeptide bridge synthesis. This protein is a key
      factor in the determination of beta-lactam resistance in MRSA, and our findings
      provide a new strategy for combating MRSA.

PMID- 23166603
TI  - Indirect methods produce higher estimates of fine root production and turnover
      rates than direct methods.
AB  - The production and turnover of fine roots play substantial roles in the
      biogeochemical cycles of terrestrial ecosystems. However, the disparity among the
      estimates of both production and turnover, particularly due to technical
      limitations, has been debated for several decades. Here, we conducted a meta
      analysis to compare published estimates of fine root production and turnover
      rates derived from different methods at the same sites and at the same sampling
      time. On average, the estimates of fine root production and turnover rates were
      87% and 124% higher, respectively, by indirect methods than by direct methods.
      The substantially higher fine root production and turnover estimated by indirect
      methods, on which most global carbon models are based, indicate the necessity of
      re-assessing the global carbon model predictions for atmospheric carbon
      sequestration in soils as a result of the production and turnover of fine roots.

PMID- 23166604
TI  - Osteopontin level in synovial fluid is associated with the severity of joint pain
      and cartilage degradation after anterior cruciate ligament rupture.
AB  - OBJECTIVE: To explore the molecular function of Osteopontin (OPN) in the
      pathogenesis of human OA, we compared the expression levels of OPN in synovial
      fluid with clinical parameters such as arthroscopic observation of cartilage
      damage and joint pain after joint injury. METHODS: Synovial fluid was obtained
      from patients who underwent anterior cruciate ligament (ACL) reconstruction
      surgery from 2009 through 2011 in our university hospital. The amounts of intact
      OPN (OPN Full) and it's N-terminal fragment (OPN N-half) in synovial fluid from
      each patient were quantified by ELISA and compared with clinical parameters such
      as severity of articular cartilage damage (TMDU cartilage score) and severity of
      joint pain (Visual Analogue Scale and Lysholm score). RESULTS: Within a month
      after ACL rupture, both OPN Full and N-half levels in patient synovial fluid were
      positively correlated with the severity of joint pain. In contrast, patients with
      ACL injuries greater than one month ago felt less pain if they had higher amounts
      of OPN N-half in synovial fluid. OPN Full levels were positively correlated with
      articular cartilage damage in lateral tibial plateau. CONCLUSION: Our data
      suggest that OPN Full and N-half have distinct functions in articular cartilage
      homeostasis and in human joint pain.

PMID- 23166605
TI  - 3-dimensional examination of the adult mouse subventricular zone reveals lineage
      specific microdomains.
AB  - Recent studies suggest that the subventricular zone (SVZ) of the lateral
      ventricle is populated by heterogeneous populations of stem and progenitor cells
      that, depending on their exact location, are biased to acquire specific neuronal
      fates. This newly described heterogeneity of SVZ stem and progenitor cells
      underlines the necessity to develop methods for the accurate quantification of
      SVZ stem and progenitor subpopulations. In this study, we provide 3-dimensional
      topographical maps of slow cycling "stem" cells and progenitors based on their
      unique cell cycle properties. These maps revealed that both cell populations are
      present throughout the lateral ventricle wall as well as in discrete regions of
      the dorsal wall. Immunodetection of transcription factors expressed in defined
      progenitor populations further reveals that divergent lineages have clear
      regional enrichments in the rostro-caudal as well as in the dorso-ventral span of
      the lateral ventricle. Thus, progenitors expressing Tbr2 and Dlx2 were confined
      to dorsal and dorso-lateral regions of the lateral ventricle, respectively, while
      Mash1+ progenitors were more homogeneously distributed. All cell populations were
      enriched in the rostral-most region of the lateral ventricle. This diversity and
      uneven distribution greatly impede the accurate quantification of SVZ progenitor
      populations. This is illustrated by measuring the coefficient of error of
      estimates obtained by using increasing section sampling interval. Based on our
      empirical data, we provide such estimates for all progenitor populations
      investigated in this study. These can be used in future studies as guidelines to
      judge if the precision obtained with a sampling scheme is sufficient to detect
      statistically significant differences between experimental groups if a biological
      effect is present. Altogether, our study underlines the need to consider the SVZ
      of the lateral ventricle as a complex 3D structure and define methods to
      accurately assess neural stem cells or progenitor diversity and population sizes
      in physiological or experimental paradigms.

PMID- 23166606
TI  - Palmitoylation at two cysteine clusters on the C-terminus of GluN2A and GluN2B
      differentially control synaptic targeting of NMDA receptors.
AB  - Palmitoylation of NMDARs occurs at two distinct cysteine clusters in the carboxyl
      terminus of GluN2A and GluN2B subunits that differentially regulates retention in
      the Golgi apparatus and surface expression of NMDARs. Mutations of
      palmitoylatable cysteine residues in the membrane-proximal cluster to non
      palmitoylatable serines leads to a reduction in the surface expression of
      recombinant NMDARs via enhanced internalization of the receptors. Mutations in a
      cluster of cysteines in the middle of the carboxyl-terminus of GluN2A and GluN2B,
      leads to an increase in the surface expression of NMDARs via an increase in post
      Golgi trafficking. Using a quantitative electrophysiological assay, we
      investigated whether palmitoylation of GluN2 subunits and the differential
      regulation of surface expression affect functional synaptic incorporation of
      NMDARs. We show that a reduction in surface expression due to mutations in the
      membrane-proximal cluster translates to a reduction in synaptic expression of
      NMDARs. However, increased surface expression induced by mutations in the cluster
      of cysteines that regulates post-Golgi trafficking of NMDARs does not increase
      the synaptic pool of NMDA receptors, indicating that the number of synaptic
      receptors is tightly regulated.

PMID- 23166607
TI  - Tissue damage disrupts developmental progression and ecdysteroid biosynthesis in
      Drosophila.
AB  - In humans, chronic inflammation, severe injury, infection and disease can result
      in changes in steroid hormone titers and delayed onset of puberty; however the
      pathway by which this occurs remains largely unknown. Similarly, in insects
      injury to specific tissues can result in a global developmental delay (e.g.
      prolonged larval/pupal stages) often associated with decreased levels of ecdysone
      - a steroid hormone that regulates developmental transitions in insects. We use
      Drosophila melanogaster as a model to examine the pathway by which tissue injury
      disrupts developmental progression. Imaginal disc damage inflicted early in
      larval development triggers developmental delays while the effects are minimized
      in older larvae. We find that the switch in injury response (e.g. delay/no delay)
      is coincident with the mid-3rd instar transition - a developmental time-point
      that is characterized by widespread changes in gene expression and marks the
      initial steps of metamorphosis. Finally, we show that developmental delays
      induced by tissue damage are associated with decreased expression of genes
      involved in ecdysteroid synthesis and signaling.

PMID- 23166608
TI  - Inconsistent definitions for intention-to-treat in relation to missing outcome
      data: systematic review of the methods literature.
AB  - BACKGROUND: Authors of randomized trial reports seem to hold a variety of views
      regarding the relationship between missing outcome data (MOD) and intention to
      treat (ITT). The objectives of this study were to systematically investigate how
      authors of methodology articles define ITT in the presence of MOD, how they
      recommend handling MOD under ITT, and to make a proposal for potential
      improvement in the definition and use of ITT in relation to MOD. METHODS AND
      FINDINGS: We systematically searched MEDLINE in February 2009 for methodological
      articles written in English that devoted at least one paragraph to ITT and two
      other paragraphs to either ITT or MOD. We excluded original trial reports,
      observational studies, and clinical systematic reviews. Working in teams of two,
      we independently extracted relevant information from each eligible article. Of
      1007 titles and abstracts reviewed, 66 articles met eligibility criteria. Five
      (8%) did not provide a definition of ITT; 25 (38%) mentioned MOD but did not
      discuss its relationship to ITT; and 36 (55%) discussed the relationship of MOD
      with ITT. These 36 articles described one or more of three statements: complete
      follow-up is required for ITT (58%); ITT and MOD are separate issues (17%); and
      ITT requires a specific strategy for handling MOD (78%); 17 (47%) endorsed more
      than one relationship. The most frequently mentioned strategies for handling MOD
      within ITT were: using the last outcome carried forward (50%); sensitivity
      analysis (50%); and use of available data to impute missing data (46%).
      CONCLUSION: We found that there is no consensus on the definition of ITT in
      relation to MOD. For conceptual clarity, we suggest that both reports of
      randomized trials and systematic reviews separately consider and describe how
      they deal with participants with complete data and those with MOD.

PMID- 23166609
TI  - Building a statistical model for predicting cancer genes.
AB  - More than 400 cancer genes have been identified in the human genome. The list is
      not yet complete. Statistical models predicting cancer genes may help with
      identification of novel cancer gene candidates. We used known prostate cancer
      (PCa) genes (identified through KnowledgeNet) as a training set to build a binary
      logistic regression model identifying PCa genes. Internal and external validation
      of the model was conducted using a validation set (also from KnowledgeNet),
      permutations, and external data on genes with recurrent prostate tumor mutations.
      We evaluated a set of 33 gene characteristics as predictors. Sixteen of the
      original 33 predictors were significant in the model. We found that a typical PCa
      gene is a prostate-specific transcription factor, kinase, or phosphatase with
      high interindividual variance of the expression level in adjacent normal prostate
      tissue and differential expression between normal prostate tissue and primary
      tumor. PCa genes are likely to have an antiapoptotic effect and to play a role in
      cell proliferation, angiogenesis, and cell adhesion. Their proteins are likely to
      be ubiquitinated or sumoylated but not acetylated. A number of novel PCa
      candidates have been proposed. Functional annotations of novel candidates
      identified antiapoptosis, regulation of cell proliferation, positive regulation
      of kinase activity, positive regulation of transferase activity, angiogenesis,
      positive regulation of cell division, and cell adhesion as top functions. We
      provide the list of the top 200 predicted PCa genes, which can be used as
      candidates for experimental validation. The model may be modified to predict
      genes for other cancer sites.

PMID- 23166611
TI  - mRNA and DNA detection of human papillomaviruses in women of all ages attending
      two colposcopy clinics.
AB  - OBJECTIVE: HPV infection is a common finding, especially in young women while the
      majority of infections are cleared within a short time interval. The aim of this
      study was to examine the efficacy of HPV DNA and mRNA testing in a population
      attending colposcopy units of two University hospitals. METHODS: 1173 liquid
      based cervical samples from two colposcopy clinics were tested for HPV DNA
      positivity using a commercial typing kit and HPV E6/E7 mRNA positivity with a
      flow cytometry based commercial kit. Statistic measures were calculated for both
      molecular tests and morphological cytology and colposcopy diagnosis according to
      histology results. RESULTS: HPV DNA, high-risk HPV DNA, HPV16 or 18 DNA and HPV
      mRNA was detected in 55.5%, 50.6%, 20.1% and 29.7% of the cervical smears
      respectively. Concordance between the DNA and the mRNA test was 71.6% with their
      differences being statistically significant. Both tests' positivity increased
      significantly as lesion grade progressed and both displayed higher positivity
      rates in samples from women under 30 years old. mRNA testing displayed similar
      NPV, slightly lower sensitivity but significantly higher specificity and PPV than
      DNA testing, except only when DNA positivity for either HPV16 or 18 was used.
      CONCLUSIONS: Overall mRNA testing displayed higher clinical efficacy than DNA
      testing, either when used as a reflex test or as an ancillary test combined with
      morphology. Due to enhanced specificity of mRNA testing and its comparable
      sensitivity in ages under 25 or 30 years old, induction of mRNA testing in young
      women could be feasible if a randomized trial verifies these results.

PMID- 23166610
TI  - Transcutaneous application of carbon dioxide (CO2) induces mitochondrial
      apoptosis in human malignant fibrous histiocytoma in vivo.
AB  - Mitochondria play an essential role in cellular energy metabolism and apoptosis.
      Previous studies have demonstrated that decreased mitochondrial biogenesis is
      associated with cancer progression. In mitochondrial biogenesis, peroxisome
      proliferator-activated receptor gamma coactivator-1 alpha (PGC-1alpha) regulates
      the activities of multiple nuclear receptors and transcription factors involved
      in mitochondrial proliferation. Previously, we showed that overexpression of PGC
      1alpha leads to mitochondrial proliferation and induces apoptosis in human
      malignant fibrous histiocytoma (MFH) cells in vitro. We also demonstrated that
      transcutaneous application of carbon dioxide (CO(2)) to rat skeletal muscle
      induces PGC-1alpha expression and causes an increase in mitochondrial
      proliferation. In this study, we utilized a murine model of human MFH to
      determine the effect of transcutaneous CO(2) exposure on PGC-1alpha expression,
      mitochondrial proliferation and cellular apoptosis. PGC-1alpha expression was
      evaluated by quantitative real-time PCR, while mitochondrial proliferation was
      assessed by immunofluorescence staining and the relative copy number of
      mitochondrial DNA (mtDNA) was assessed by real-time PCR. Immunofluorescence
      staining and DNA fragmentation assays were used to examine mitochondrial
      apoptosis. We also evaluated the expression of mitochondrial apoptosis related
      proteins, such as caspases, cytochorome c and Bax, by immunoblot analysis. We
      show that transcutaneous application of CO(2) induces PGC-1alpha expression, and
      increases mitochondrial proliferation and apoptosis of tumor cells, significantly
      reducing tumor volume. Proteins involved in the mitochondrial apoptotic cascade,
      including caspase 3 and caspase 9, were elevated in CO(2) treated tumors compared
      to control. We also observed an enrichment of cytochrome c in the cytoplasmic
      fraction and Bax protein in the mitochondrial fraction of CO(2) treated tumors,
      highlighting the involvement of mitochondria in apoptosis. These data indicate
      that transcutaneous application of CO(2) may represent a novel therapeutic tool
      in the treatment of human MFH.

PMID- 23166612
TI  - A U-Box E3 ubiquitin ligase, PUB20, interacts with the Arabidopsis G-protein beta
      subunit, AGB1.
AB  - An Arabidopsis U-box E3 ubiquitin ligase Plant U-box 20 (PUB20; alternatively
      called AtCMPG1) was identified as a possible interactor of the Arabidopsis G
      protein beta subunit, AGB1, by yeast two-hybrid screening. A bimolecular
      fluorescence complementation (BiFC) assay showed that PUB20 interacted with AGB1
      in the nuclei and the cytosol. The expression levels of PUB20 and its closest
      homolog, PUB21 were stable under many conditions. GUS driven by the PUB20
      promoter was active in anthers, pollen, premature seeds and receptacles and GUS
      driven by the PUB21 promoter was active in anthers and funiculi. PUB20 was found
      to have autoubiquitination activity in vitro.

PMID- 23166613
TI  - Label-free single-particle imaging of the influenza virus by objective-type total
      internal reflection dark-field microscopy.
AB  - Here we report label-free optical imaging of single particles of the influenza
      virus attached on a glass surface with a simple objective-type total internal
      reflection dark-field microscopy (TIRDFM). The capability of TIRDFM for the
      imaging of single viral particles was confirmed from fine correlation of the
      TIRDFM images with fluorescent immunostaining image and scanning electron
      microscopy image. The density of scattering spots in the TIRDFM images showed a
      good linearity against the virus concentration, giving the limit of detection as
      1.2*10(4) plaque-forming units per milliliter. Our label-free optical imaging
      method does require neither elaborated sample preparation nor complex optical
      systems, offering a good platform for rapid and sensitive counting of viral
      particles.

PMID- 23166614
TI  - Lipoteichoic acid from Staphylococcus aureus induces lung endothelial cell
      barrier dysfunction: role of reactive oxygen and nitrogen species.
AB  - Tunneled central venous catheters (TCVCs) are used for dialysis access in 82% of
      new hemodialysis patients and are rapidly colonized with Gram-positive organism
      (e.g. Staphylococcus aureus) biofilm, a source of recurrent infections and
      chronic inflammation. Lipoteichoic acid (LTA), a cell wall ribitol polymer from
      Gram-positive organisms, mediates inflammation through the Toll-like receptor 2
      (TLR2). The effect of LTA on lung endothelial permeability is not known. We
      tested the hypothesis that LTA from Staphylococcus aureus induces alterations in
      the permeability of pulmonary microvessel endothelial monolayers (PMEM) that
      result from activation of TLR2 and are mediated by reactive oxygen/nitrogen
      species (RONS). The permeability of PMEM was assessed by the clearance rate of
      Evans blue-labeled albumin, the activation of the TLR2 pathway was assessed by
      Western blot, and the generation of RONS was measured by the fluorescence of
      oxidized dihydroethidium and a dichlorofluorescein derivative. Treatment with LTA
      or the TLR2 agonist Pam((3))CSK((4)) induced significant increases in albumin
      permeability, IkappaBalpha phosphorylation, IRAK1 degradation, RONS generation,
      and endothelial nitric oxide synthase (eNOS) activation (as measured by the p
      eNOS(ser1177):p-eNOS(thr495) ratio). The effects on permeability and RONS were
      effectively prevented by co-administration of the superoxide scavenger Tiron, the
      peroxynitrite scavenger Urate, or the eNOS inhibitor L-NAME and these effects as
      well as eNOS activation were reduced or prevented by pretreatment with an IRAK1/4
      inhibitor. The results indicate that the activation of TLR2 and the generation of
      ROS/RNS mediates LTA-induced barrier dysfunction in PMEM.

PMID- 23166615
TI  - Genome-wide survey and expression analysis of amino acid transporter gene family
      in rice (Oryza sativa L.).
AB  - BACKGROUND: Amino acid transporters (AATs) that transport amino acids across
      cellular membranes are essential for plant growth and development. To date, a
      genome-wide overview of the AAT gene family in rice is not yet available.
      METHODOLOGY/PRINCIPAL FINDINGS: In this study, a total of 85 AAT genes were
      identified in rice genome and were classified into eleven distinct subfamilies
      based upon their sequence composition and phylogenetic relationship. A large
      number of OsAAT genes were expanded via gene duplication, 23 and 24 OsAAT genes
      were tandemly and segmentally duplicated, respectively. Comprehensive analyses
      were performed to investigate the expression profiles of OsAAT genes in various
      stages of vegetative and reproductive development by using data from EST,
      Microarrays, MPSS and Real-time PCR. Many OsAAT genes exhibited abundant and
      tissue-specific expression patterns. Moreover, 21 OsAAT genes were found to be
      differentially expressed under the treatments of abiotic stresses. Comparative
      analysis indicates that 26 AAT genes with close evolutionary relationships
      between rice and Arabidopsis exhibited similar expression patterns.
      CONCLUSIONS/SIGNIFICANCE: This study will facilitate further studies on OsAAT
      family and provide useful clues for functional validation of OsAATs.

PMID- 23166616
TI  - Study of association of CD40-CD154 gene polymorphisms with disease susceptibility
      and cardiovascular risk in Spanish rheumatoid arthritis patients.
AB  - OBJECTIVE: Rheumatoid arthritis (RA) is a chronic inflammatory disease associated
      with increased cardiovascular (CV) mortality. Since CD40-CD154 binding has direct
      consequences on inflammation process initiation, we aimed to replicate previous
      findings related to disease susceptibility in Spanish RA population. Furthermore,
      as the major complication in RA disease patients is the development of CV events
      due to accelerated atherosclerosis, and elevated levels of CD40L/CD154 are
      present in patients with acute myocardial infarction, we assessed the potential
      association of CD40 and CD154/CD40L gene variants with CV risk in Spanish RA
      patients. METHODS: One thousand five hundred and seventy-five patients fulfilling
      the 1987 ACR classification criteria for RA and 1600 matched controls were
      genotyped for the CD40 rs1883832, rs4810485 and rs1535045 and CD154 rs3092952 and
      rs3092920 gene polymorphisms, using predesigned TaqMan single nucleotide
      polymorphism genotyping assays. Afterwards, we investigated the influence of CD40
      CD154 gene variants in the development of CV events. Also, in a subgroup of 273
      patients without history of CV events, we assessed the influence of these
      polymorphisms in the risk of subclinical atherosclerosis determined by carotid
      ultrasonography. RESULTS: Nominally significant differences in the allele
      frequencies for the rs1883832 CD40 gene polymorphism between RA patients and
      controls were found (p=0.038). Although we did not observe a significant
      association of CD40-CD154 gene variants with the development of CV events, an
      ANCOVA model adjusted for sex, age at the time of the ultrasonography assessment,
      follow-up time, traditional CV risk factors and anti-cyclic citrullinated peptide
      antibodies disclosed a significant association (p=0.0047) between CD40 rs1535045
      polymorphism and carotid intima media thickness, a surrogate marker of
      atherosclerosis. CONCLUSION: Data from our pilot study indicate a potential
      association of rs1883832 CD40 gene polymorphism with susceptibility to RA. Also,
      the CD40 rs1535045 gene variant may influence development of subclinical
      atherosclerosis in RA patients.

PMID- 23166617
TI  - Your space or mine? Mapping self in time.
AB  - While humans are capable of mentally transcending the here and now, this faculty
      for mental time travel (MTT) is dependent upon an underlying cognitive
      representation of time. To this end, linguistic, cognitive and behavioral
      evidence has revealed that people understand abstract temporal constructs by
      mapping them to concrete spatial domains (e.g. past=backward, future=forward).
      However, very little research has investigated factors that may determine the
      topographical characteristics of these spatiotemporal maps. Guided by the
      imperative role of episodic content for retrospective and prospective thought
      (i.e., MTT), here we explored the possibility that the spatialization of time is
      influenced by the amount of episodic detail a temporal unit contains. In two
      experiments, participants mapped temporal events along mediolateral (Experiment
      1) and anterioposterior (Experiment 2) spatial planes. Importantly, the temporal
      units varied in self-relevance as they pertained to temporally proximal or distal
      events in the participant's own life, the life of a best friend or the life of an
      unfamiliar other. Converging evidence from both experiments revealed that the
      amount of space used to represent time varied as a function of target (self, best
      friend or unfamiliar other) and temporal distance. Specifically, self-time was
      represented as occupying more space than time pertaining to other targets, but
      only for temporally proximal events. These results demonstrate the malleability
      of space-time mapping and suggest that there is a self-specific conceptualization
      of time that may influence MTT as well as other temporally relevant cognitive
      phenomena.

PMID- 23166618
TI  - A novel strain D5 isolated from Acacia confusa.
AB  - We isolated a novel strain D5 from nodules of Acacia confusa. Under strict
      sterile conditions the strain could successfully nodulate Acacia confusa, A.
      crassicarpa and A. mangium, with nitrogenase activity ranging from 18.90 to 19.86
      nmol.g(-1).min(-1). In the phylogenetic tree based on a complete 16S rRNA gene
      sequence, the sequence of strain D5 shared 99% homology with that of four species
      of genus Pseudomonas. The 685 bp nodA fragment amplified from strain D5 shared
      95% homology with the nodA sequence of 9 species of genus Bradyrhizobium, with a
      genetic distance of 0.01682. The 740 bp nifH gene fragment was amplified from
      strain D5. This strain D5 nifH gene and Bradyrhizobium spp. formed a branch,
      showing 98% homology and a genetic distance of 0. The homology between this
      branch and the Bradyrhizobium spp. DG in another branch was 99%, with a genetic
      distance of 0.007906. These results indicate that this strain D5 is a new type of
      nitrogen-fixing bacterium.

PMID- 23166619
TI  - Role of human sec63 in modulating the steady-state levels of multi-spanning
      membrane proteins.
AB  - The Sec61 translocon of the endoplasmic reticulum (ER) membrane forms an aqueous
      pore, allowing polypeptides to be transferred across or integrated into
      membranes. Protein translocation into the ER can occur co- and
      posttranslationally. In yeast, posttranslational translocation involves the
      heptameric translocase complex including its Sec62p and Sec63p subunits. The
      mammalian ER membrane contains orthologs of yeast Sec62p and Sec63p, but their
      function is poorly understood. Here, we analyzed the effects of excess and
      deficit Sec63 on various ER cargoes using human cell culture systems. The
      overexpression of Sec63 reduces the steady-state levels of viral and cellular
      multi-spanning membrane proteins in a cotranslational mode, while soluble and
      single-spanning ER reporters are not affected. Consistent with this, the knock
      down of Sec63 increases the steady-state pools of polytopic ER proteins,
      suggesting a substrate-specific and regulatory function of Sec63 in ER import.
      Overexpressed Sec63 exerts its down-regulating activity on polytopic protein
      levels independent of its Sec62-interacting motif, indicating that it may not act
      in conjunction with Sec62 in human cells. The specific action of Sec63 is further
      sustained by our observations that the up-regulation of either Sec62 or two other
      ER proteins with lumenal J domains, like ERdj1 and ERdj4, does not compromise the
      steady-state level of a multi-spanning membrane reporter. A J domain-specific
      mutation of Sec63, proposed to weaken its interaction with the ER resident BiP
      chaperone, reduces the down-regulating capacity of excess Sec63, suggesting an
      involvement of BiP in this process. Together, these results suggest that Sec63
      may perform a substrate-selective quantity control function during
      cotranslational ER import.

PMID- 23166620
TI  - Circulating MACC1 transcripts in colorectal cancer patient plasma predict
      metastasis and prognosis.
AB  - BACKGROUND: Metastasis is the most frequent cause of treatment failure and death
      in colorectal cancer. Early detection of tumors and metastases is crucial for
      improving treatment strategies and patient outcome. Development of reliable
      biomarkers and simple tests routinely applicable in the clinic for detection,
      prognostication, and therapy monitoring is of special interest. We recently
      identified the novel gene Metastasis-Associated in Colon Cancer 1 (MACC1), a key
      regulator of the HGF/Met-pathway. MACC1 is a strong prognostic biomarker for
      colon cancer metastasis and allows identification of high-risk subjects in early
      stages, when determined in patients' primary tumors. To overcome the limitation
      of a restricted number of molecular analyses in tumor tissue, the establishment
      of a non-invasive blood test for early identification of high-risk cancer
      patients, for monitoring disease course and therapy response is strongly needed.
      METHODOLOGY/PRINCIPAL FINDINGS: For the first time, we describe a non-invasive
      assay for quantification of circulating MACC1 transcripts in blood of more than
      300 colorectal cancer patients. MACC1 transcript levels are increased in all
      disease stages of the cancer patients compared to tumor-free volunteers. Highest
      MACC1 levels were determined in individuals with metastases (all P<0.05).
      Importantly, high MACC1 levels correlate with unfavorable survival (P<.0001).
      Combining MACC1 with circulating transcripts of the metastasis gene S100A4, a
      transcriptional target of the Wnt/beta-catenin-pathway, improves survival
      prediction for newly diagnosed cancer patients. CONCLUSION/SIGNIFICANCE: This
      blood-based assay for circulating MACC1 transcripts, which can be quantitated on
      a routine basis, is clinically applicable for diagnosis, prognosis, and
      therapeutic monitoring of cancer patients. Here we demonstrate the diagnostic and
      prognostic value of circulating MACC1 transcripts in patient plasma for
      metastasis and survival. Since MACC1 represents a promising target for anti
      metastatic therapies, circulating MACC1 transcripts may prove to be an ideal read
      out for monitoring therapeutic response of future interventions targeting MACC1
      induced metastasis in cancer patients.

PMID- 23166621
TI  - ERK1/2 and p38 MAPKs are complementarily involved in estradiol 17beta-D
      glucuronide-induced cholestasis: crosstalk with cPKC and PI3K.
AB  - OBJECTIVE: The endogenous, cholestatic metabolite estradiol 17beta-D-glucuronide
      (E(2)17G) induces endocytic internalization of the canalicular transporters
      relevant to bile formation, Bsep and Mrp2. We evaluated here whether MAPKs are
      involved in this effect. DESIGN: ERK1/2, JNK1/2, and p38 MAPK activation was
      assessed by the increase in their phosphorylation status. Hepatocanalicular
      function was evaluated in isolated rat hepatocyte couplets (IRHCs) by quantifying
      the apical secretion of fluorescent Bsep and Mrp2 substrates, and in isolated,
      perfused rat livers (IPRLs), using taurocholate and 2,4-dinitrophenyl-S
      glutathione, respectively. Protein kinase participation in E(2)17G-induced
      secretory failure was assessed by co-administering selective inhibitors.
      Internalization of Bsep/Mrp2 was assessed by confocal microscopy and image
      analysis. RESULTS: E(2)17G activated all kinds of MAPKs. The PI3K inhibitor
      wortmannin prevented ERK1/2 activation, whereas the cPKC inhibitor Go6976
      prevented p38 activation, suggesting that ERK1/2 and p38 are downstream of PI3K
      and cPKC, respectively. The p38 inhibitor SB203580 and the ERK1/2 inhibitor
      PD98059, but not the JNK1/2 inhibitor SP600125, partially prevented E(2)17G
      induced changes in transporter activity and localization in IRHCs. p38 and ERK1/2
      co-inhibition resulted in additive protection, suggesting complementary
      involvement of these MAPKs. In IPRLs, E(2)17G induced endocytosis of canalicular
      transporters and a rapid and sustained decrease in bile flow and biliary
      excretion of Bsep/Mrp2 substrates. p38 inhibition prevented this initial decay,
      and the internalization of Bsep/Mrp2. Contrarily, ERK1/2 inhibition accelerated
      the recovery of biliary secretion and the canalicular reinsertion of Bsep/Mrp2.
      CONCLUSIONS: cPKC/p38 MAPK and PI3K/ERK1/2 signalling pathways participate
      complementarily in E(2)17G-induced cholestasis, through internalization and
      sustained intracellular retention of canalicular transporters, respectively.

PMID- 23166622
TI  - Electrophysiological and behavioral responses of male fall webworm moths
      (Hyphantria cunea) to Herbivory-induced mulberry (Morus alba) leaf volatiles.
AB  - Volatile organic compounds (VOCs) were collected from damaged and intact mulberry
      leaves (Morus alba L., Moraceae) and from Hyphantria cunea larvae by headspace
      absorption with Super Q columns. We identified their constituents using gas
      chromatography-mass spectrometry, and evaluated the responses of male H. cunea
      antennae to the compounds using gas chromatography-flame ionization detection
      coupled with electroantennographic detection. Eleven VOC constituents were found
      to stimulate antennae of male H. cunea moths: beta-ocimene, hexanal, cis-3
      hexenal, limonene, trans-2-hexenal, cyclohexanone, cis-2-penten-1-ol, 6-methyl-5
      hepten-2-one, 4-hydroxy-4-methyl-2-pentanone, trans-3-hexen-1-ol, and 2,4
      dimethyl-3-pentanol. Nine of these chemicals were released by intact,
      mechanically-damaged, and herbivore-damaged leaves, while cis-2-penten-1-ol was
      released only by intact and mechanically-damaged leaves and beta-ocimene was
      released only by herbivore-damaged leaves. Results from wind tunnel experiments
      conducted with volatile components indicated that male moths were significantly
      more attracted to herbivory-induced volatiles than the solvent control.
      Furthermore, male moths' attraction to a sex pheromone lure was increased by
      herbivory-induced compounds and beta-ocimene, but reduced by cis-2-penten-1-ol. A
      proof long-range field trapping experiment showed that the efficiency of sex
      pheromone lures in trapping male moths was increased by beta-ocimene and reduced
      by cis-2-penten-1-ol.

PMID- 23166623
TI  - Involvement of dynamin-related protein 1 in free fatty acid-induced INS-1-derived
      cell apoptosis.
AB  - Elevated extracellular free fatty acids (FFAs) can induce pancreatic beta cell
      apoptosis, thereby contributing to the pathogenesis of type 2 diabetes mellitus
      (T2D). Mitochondrial dysfunction has been implicated in FFA-induced beta cell
      apoptosis. However, molecular mechanisms linking mitochondrial dysfunction and
      FFA-induced beta cell apoptosis are not clear. Dynamin-related protein 1 (DRP-1)
      is a mitochondrial fission modulator. In this study, we investigated its role in
      FFA-induced INS-1 beta cell apoptosis. DRP-1 protein was promptly induced in INS
      1 cells and rat islets after stimulation by FFAs, and this DRP-1 upregulation was
      accompanied by increased INS-1 cell apoptosis. Induction of DRP-1 expression
      significantly promoted FFA-induced apoptosis in DRP-1 WT (DRP-1 wild type)
      inducible INS-1-derived cell line, but not in DRP-1K38A (a dominant negative
      mutant of DRP-1) inducible INS-1-derived cell line. To validate these in vitro
      results, we transplanted DRP-1 WT or DRP-1 K38A cells into renal capsules of
      streptozotocin (STZ)-treated diabetic mice to study the apoptosis in xenografts.
      Consistent with the in vitro results, the over-expression of DRP-1 led to
      aggravated INS-1-derived cell apoptosis triggered by FFAs. In contrast, dominant
      negative suppression of DRP-1 function as represented by DRP-1 K38A significantly
      prevented FFA-induced apoptosis in xenografts. It was further demonstrated that
      mitochondrial membrane potential decreased, while cytochrome c release, caspase-3
      activation, and generation of reactive oxygen species (ROS) were enhanced by the
      induction of DRP-1WT, but prevented by DRP-1 K38A in INS-1-derived cells under
      FFA stimulation. These results indicated that DRP-1 mediates FFA-induced INS-1
      derived cell apoptosis, suggesting that suppression of DRP-1 is a potentially
      useful therapeutic strategy for protecting against beta cell loss that leads to
      type 2 diabetes.

PMID- 23166624
TI  - Characterization of small, mononuclear blood cells from salmon having high
      phagocytic capacity and ability to differentiate into dendritic like cells.
AB  - Phagocytes are the principal component of the innate immune system, playing a key
      role in the clearance of foreign particles that include potential pathogens. In
      vertebrates, both neutrophils and mononuclear cells like monocytes, macrophages
      and dendritic cells are all professional phagocytes. In teleosts, B-lymphocytes
      also have potent phagocytic ability. We have isolated a population of small (<5
      um), mononuclear blood cells from Atlantic salmon (Salmo salar L.) not previously
      characterized. In order to identify them, we have performed morphological, gene
      expression, flow cytometry, cytochemical, ultrastructural and functional
      analyses. Interestingly, they highly express the gene encoding CD83, the most
      characteristic cell surface marker for dendritic cells in mammals, and MHC class
      II limited to professional antigen presenting cells. They did not express genes
      nor did they have cell markers for B-cells, T-cells, monocytes/macrophages or
      neutrophils as shown by qRT-PCR, flow cytometry and immunoblotting. A remarkable
      feature of these cells is their potent phagocytic capacity. Their oxygen
      independent killing mechanism, as shown by intense acid phosphatase staining, is
      supported by lack of respiratory burst and myeloperoxidase activity and the acid
      phosphatase's sensitivity to tartrate. They show a high level of morphological
      plasticity, as, upon stimulation with mitogens, they change morphology and obtain
      branching protrusions similarly to dendritic cells. We suggest, based on our
      findings, that the small, round cells described here are progenitor cells with
      potential to differentiate into dendritic like cells, although we can not exclude
      the possibility that they represent a novel cell type.

PMID- 23166626
TI  - Elevated bile acids in newborns with Biliary Atresia (BA).
AB  - Biliary Atresia (BA), a result from inflammatory destruction of the intrahepatic
      and extrahepatic bile ducts, is a severe hepatobiliary disorder unique to
      infancy. Early diagnosis and Kasai operation greatly improve the outcome of BA
      patients, which encourages the development of early screening methods. Using HPLC
      coupled tandem mass spectrometry, we detected primary bile acids content in dried
      blood spots obtained from 8 BA infants, 17 neonatal jaundice and 292 comparison
      infants at 3-4 days of life. Taurocholate (TC) was significantly elevated in
      biliary atresia infants (0.98 +/- 0.62 umol/L) compared to neonatal jaundice
      (0.47 +/- 0.30 umol/L) and comparison infants (0.43 +/- 0.40 umol/L), with
      p=0.0231 and p=0.0016 respectively. The area under receiver operating
      characteristic (ROC) curve for TC to discriminate BA and comparison infants was
      0.82 (95% confidence interval: 0.72-0.92). A cutoff of 0.63 umol/L produced a
      sensitivity of 79.1% and specificity of 62.5%. The concentrations of total bile
      acids were also raised significantly in BA compared to comparison infants (6.62
      +/- 3.89 umol/L vs 3.81 +/- 3.06 umol/L, p=0.0162), with the area under ROC curve
      of 0.75 (95% confidence interval: 0.61-0.89). No significant difference was found
      between the bile acids of neonatal jaundice and that of comparison infants. The
      early increase of bile acids indicates the presentation of BA in the immediate
      newborn period and the possibility of TC as newborn screening marker.

PMID- 23166625
TI  - Evolutionary dynamics of the interferon-induced transmembrane gene family in
      vertebrates.
AB  - Vertebrate interferon-induced transmembrane (IFITM) genes have been demonstrated
      to have extensive and diverse functions, playing important roles in the evolution
      of vertebrates. Despite observance of their functionality, the evolutionary
      dynamics of this gene family are complex and currently unknown. Here, we
      performed detailed evolutionary analyses to unravel the evolutionary history of
      the vertebrate IFITM family. A total of 174 IFITM orthologous genes and 112
      pseudogenes were identified from 27 vertebrate genome sequences. The vertebrate
      IFITM family can be divided into immunity-related IFITM (IR-IFITM), IFITM5 and
      IFITM10 sub-families in phylogeny, implying origins from three different
      progenitors. In general, vertebrate IFITM genes are located in two loci, one
      containing the IFITM10 gene, and the other locus containing IFITM5 and various
      numbers of IR-IFITM genes. Conservation of evolutionary synteny was observed in
      these IFITM genes. Significant functional divergence was detected among the three
      IFITM sub-families. No gene duplication or positive selection was found in IFITM5
      sub-family, implying the functional conservation of IFITM5 in vertebrate
      evolution, which is involved in bone formation. No IFITM5 locus was identified in
      the marmoset genome, suggesting a potential association with the tiny size of
      this monkey. The IFITM10 sub-family was divided into two groups: aquatic and
      terrestrial types. Functional divergence was detected between the two groups, and
      five IFITM10-like genes from frog were dispersed into the two groups. Both gene
      duplication and positive selection were observed in aquatic vertebrate IFITM10
      like genes, indicating that IFITM10 might be associated with the adaptation to
      aquatic environments. A large number of lineage- and species-specific gene
      duplications were observed in IR-IFITM sub-family and positive selection was
      detected in IR-IFITM of primates and rodents. Because primates have experienced a
      long history of viral infection, such rapid expansion and positive selection
      suggests that the evolution of primate IR-IFITM genes is associated with broad
      spectrum antiviral activity.

PMID- 23166627
TI  - A new protein superfamily: TPPP-like proteins.
AB  - The introduction of the term 'Tubulin Polymerization Promoting Protein (TPPP)
      like proteins' is suggested. They constitute a eukaryotic protein superfamily,
      characterized by the presence of the p25alpha domain (Pfam05517, IPR008907), and
      named after the first identified member, TPPP/p25, exhibiting microtubule
      stabilizing function. TPPP-like proteins can be grouped on the basis of two
      characteristics: the length of their p25alpha domain, which can be long, short,
      truncated or partial, and the presence or absence of additional domain(s). TPPPs,
      in the strict sense, contain no other domains but one long or short p25alpha one
      (long- and short-type TPPPs, respectively). Proteins possessing truncated
      p25alpha domain are first described in this paper. They evolved from the long
      type TPPPs and can be considered as arthropod-specific paralogs of long-type
      TPPPs. Phylogenetic analysis shows that the two groups (long-type and truncated
      TPPPs) split in the common ancestor of arthropods. Incomplete p25alpha domains
      can be found in multidomain TPPP-like proteins as well. The various subfamilies
      occur with a characteristic phyletic distribution: e. g., animal
      genomes/proteomes contain almost without exception long-type TPPPs; the
      multidomain apicortins occur almost exclusively in apicomplexan parasites. There
      are no data about the physiological function of these proteins except two human
      long-type TPPP paralogs which are involved in developmental processes of the
      brain and the musculoskeletal system, respectively. I predict that the
      superfamily members containing long or partial p25alpha domain are often
      intrinsically disordered proteins, while those with short or truncated domain(s)
      are structurally ordered. Interestingly, members of this superfamily connected or
      maybe connected to diseases are intrinsically disordered proteins.

PMID- 23166628
TI  - Metformin inhibits glutaminase activity and protects against hepatic
      encephalopathy.
AB  - AIM: To investigate the influence of metformin use on liver dysfunction and
      hepatic encephalopathy in a retrospective cohort of diabetic cirrhotic patients.
      To analyze the impact of metformin on glutaminase activity and ammonia production
      in vitro. METHODS: Eighty-two cirrhotic patients with type 2 diabetes were
      included. Forty-one patients were classified as insulin sensitizers experienced
      (metformin) and 41 as controls (cirrhotic patients with type 2 diabetes mellitus
      without metformin treatment). Baseline analysis included: insulin, glucose,
      glucagon, leptin, adiponectin, TNFr2, AST, ALT. HOMA-IR was calculated. Baseline
      HE risk was calculated according to minimal hepatic encephalopathy, oral
      glutamine challenge and mutations in glutaminase gene. We performed an
      experimental study in vitro including an enzymatic activity assay where
      glutaminase inhibition was measured according to different metformin
      concentrations. In Caco2 cells, glutaminase activity inhibition was evaluated by
      ammonia production at 24, 48 and 72 hours after metformina treatment. RESULTS:
      Hepatic encephalopathy was diagnosed during follow-up in 23.2% (19/82): 4.9%
      (2/41) in patients receiving metformin and 41.5% (17/41) in patients without
      metformin treatment (logRank 9.81; p=0.002). In multivariate analysis, metformin
      use [H.R.11.4 (95% CI: 1.2-108.8); p=0.034], age at diagnosis [H.R.1.12 (95% CI:
      1.04-1.2); p=0.002], female sex [H.R.10.4 (95% CI: 1.5-71.6); p=0.017] and HE
      risk [H.R.21.3 (95% CI: 2.8-163.4); p=0.003] were found independently associated
      with hepatic encephalopathy. In the enzymatic assay, glutaminase activity
      inhibition reached 68% with metformin 100 mM. In Caco2 cells, metformin (20 mM)
      decreased glutaminase activity up to 24% at 72 hours post-treatment (p<0.05).
      CONCLUSIONS: Metformin was found independently related to overt hepatic
      encephalopathy in patients with type 2 diabetes mellitus and high risk of hepatic
      encephalopathy. Metformin inhibits glutaminase activity in vitro. Therefore,
      metformin use seems to be protective against hepatic encephalopathy in diabetic
      cirrhotic patients.

PMID- 23166629
TI  - Autoinactivation of the stargazin-AMPA receptor complex: subunit-dependency and
      independence from physical dissociation.
AB  - Agonist responses and channel kinetics of native alpha-amino-3-hydroxy-5-methyl-4
      isoxazole propionic acid (AMPA) receptors are modulated by transmembrane
      accessory proteins. Stargazin, the prototypical accessory protein, decreases
      desensitization and increases agonist potency at AMPA receptors. Furthermore, in
      the presence of stargazin, the steady-state responses of AMPA receptors show a
      gradual decline at higher glutamate concentrations. This "autoinactivation" has
      been assigned to physical dissociation of the stargazin-AMPA receptor complex and
      suggested to serve as a protective mechanism against overactivation. Here, we
      analyzed autoinactivation of GluA1-A4 AMPA receptors (all flip isoform) expressed
      in the presence of stargazin. Homomeric GluA1, GluA3, and GluA4 channels showed
      pronounced autoinactivation indicated by the bell-shaped steady-state dose
      response curves for glutamate. In contrast, homomeric GluA2i channels did not
      show significant autoinactivation. The resistance of GluA2 to autoinactivation
      showed striking dependence on the splice form as GluA2-flop receptors displayed
      clear autoinactivation. Interestingly, the resistance of GluA2-flip containing
      receptors to autoinactivation was transferred onto heteromeric receptors in a
      dominant fashion. To examine the relationship of autoinactivation to physical
      separation of stargazin from the AMPA receptor, we analyzed a GluA4-stargazin
      fusion protein. Notably, the covalently linked complex and separately expressed
      proteins expressed a similar level of autoinactivation. We conclude that
      autoinactivation is a subunit and splice form dependent property of AMPA receptor
      stargazin complexes, which involves structural rearrangements within the complex
      rather than any physical dissociation.

PMID- 23166631
TI  - Evidence for genetic variation in human mate preferences for sexually dimorphic
      physical traits.
AB  - Intersexual selection has been proposed as an important force in shaping a number
      of morphological traits that differ between human populations and/or between the
      sexes. Important to these accounts is the source of mate preferences for such
      traits, but this has not been investigated. In a large sample of twins, we assess
      forced-choice, dichotomous mate preferences for height, skin colour, hair colour
      and length, chest hair, facial hair, and breast size. Across the traits,
      identical twins reported more similar preferences than nonidentical twins,
      suggesting genetic effects. However, the relative magnitude of estimated genetic
      and environmental effects differed greatly and significantly between different
      trait preferences, with heritability estimates ranging from zero to 57%.

PMID- 23166630
TI  - Conformational changes of blood ACE in chronic uremia.
AB  - BACKGROUND: The pattern of binding of monoclonal antibodies (mAbs) to 16 epitopes
      on human angiotensin I-converting enzyme (ACE) comprise a conformational ACE
      fingerprint and is a sensitive marker of subtle protein conformational changes.
      HYPOTHESIS: Toxic substances in the blood of patients with uremia due to End
      Stage Renal Disease (ESRD) can induce local conformational changes in the ACE
      protein globule and alter the efficacy of ACE inhibitors. METHODOLOGY/PRINCIPAL
      FINDINGS: The recognition of ACE by 16 mAbs to the epitopes on the N and C
      domains of ACE was estimated using an immune-capture enzymatic plate
      precipitation assay. The precipitation pattern of blood ACE by a set of mAbs was
      substantially influenced by the presence of ACE inhibitors with the most dramatic
      local conformational change noted in the N-domain region recognized by mAb 1G12.
      The "short" ACE inhibitor enalaprilat (tripeptide analog) and "long" inhibitor
      teprotide (nonapeptide) produced strikingly different mAb 1G12 binding with
      enalaprilat strongly increasing mAb 1G12 binding and teprotide decreasing
      binding. Reduction in S-S bonds via glutathione and dithiothreitol treatment
      increased 1G12 binding to blood ACE in a manner comparable to enalaprilat. Some
      patients with uremia due to ESRD exhibited significantly increased mAb 1G12
      binding to blood ACE and increased ACE activity towards angiotensin I accompanied
      by reduced ACE inhibition by inhibitory mAbs and ACE inhibitors.
      CONCLUSIONS/SIGNIFICANCE: The estimation of relative mAb 1G12 binding to blood
      ACE detects a subpopulation of ESRD patients with conformationally changed ACE,
      which activity is less suppressible by ACE inhibitors. This parameter may
      potentially serve as a biomarker for those patients who may need higher
      concentrations of ACE inhibitors upon anti-hypertensive therapy.

PMID- 23166632
TI  - Effect of pullulan nanoparticle surface charges on HSA complexation and drug
      release behavior of HSA-bound nanoparticles.
AB  - Nanoparticle (NP) compositions such as hydrophobicity and surface charge are
      vital to determine the presence and amount of human serum albumin (HSA) binding.
      The HSA binding influences drug release, biocompatibility, biodistribution, and
      intercellular trafficking of nanoparticles (NPs). Here, we prepared 2 kinds of
      nanomaterials to investigate HSA binding and evaluated drug release of HSA-bound
      NPs. Polysaccharides (pullulan) carboxyethylated to provide ionic derivatives
      were then conjugated to cholesterol groups to obtain cholesterol-modified
      carboxyethyl pullulan (CHCP). Cholesterol-modified pullulan (CHP) conjugate was
      synthesized with a similar degree of substitution of cholesterol moiety to CHCP.
      CHCP formed self-aggregated NPs in aqueous solution with a spherical structure
      and zeta potential of -19.9 +/- 0.23 mV, in contrast to -1.21 +/- 0.12 mV of CHP
      NPs. NPs could quench albumin fluorescence intensity with maximum emission
      intensity gradually decreasing up to a plateau at 9 to 12 h. Binding constants
      were 1.12 * 10(5) M(-1) and 0.70 * 10(5) M(-1) to CHP and CHCP, respectively, as
      determined by Stern-Volmer analysis. The complexation between HSA and NPs was a
      gradual process driven by hydrophobic force and inhibited by NP surface charge
      and shell-core structure. HSA conformation was altered by NPs with reduction of
      alpha-helical content, depending on interaction time and particle surface
      charges. These NPs could represent a sustained release carrier for mitoxantrone
      in vitro, and the bound HSA assisted in enhancing sustained drug release.

PMID- 23166633
TI  - Exon 1 disruption alters tissue-specific expression of mouse p53 and results in
      selective development of B cell lymphomas.
AB  - p53 is a tumor suppressor gene mutated in >50% of human cancers, while p53
      deficiency in mice results in cancers and accelerated mortality. Thymic T cell
      lymphoma is the most common malignancy in p53-deficient mice, making it difficult
      to study the role of p53 in other malignancies. To overcome this limitation, we
      attempted to generate mice with a reversible p53 knockout (p53(rev/rev)) by
      inserting a floxed transcriptional stop into the first exon of p53, anticipating
      that this would allow tissue-specific Cre-mediated expression of p53. Contrary to
      expectations, functional p53 protein was expressed in the thymus and multiple
      other tissues of p53(rev/rev) mice in the absence of Cre, whereas B cells
      expressed p53 protein only in the presence of B cell-specific CD19-Cre. In the
      absence of Cre, 76% of p53(rev/rev) mice developed splenic marginal zone B cell
      lymphomas, indicating sensitivity of this B cell subset to transformation caused
      by p53 deficiency. 5'-RACE identified p53 mRNA transcribed from a novel start
      site utilized in thymocytes but not normal B cells or B cell lymphomas from
      p53(rev/rev) mice. The p53(rev/rev) mouse thus demonstrates an effect of p53
      deficiency in development of splenic marginal zone lymphomas and provides a model
      for study of p53-deficient human B cell lymphomas.

PMID- 23166634
TI  - Spirooxindole derivative SOID-8 induces apoptosis associated with inhibition of
      JAK2/STAT3 signaling in melanoma cells.
AB  - Melanoma is generally refractory to current chemotherapy, thus new treatment
      strategies are needed. In this study, we synthesized a series of spirooxindole
      derivatives (SOID-1 to SOID-12) and evaluated their antitumor effects on
      melanoma. Among the 12 spirooxindole derivatives, SOID-8 showed the strongest
      antitumor activity by viability screening. SOID-8 inhibited viability of A2058,
      A375, SK-MEL-5 and SK-MEL-28 human melanoma cells in a dose- and time-dependent
      manner. SOID-8 also induced apoptosis of these tumor cells, which was confirmed
      by positive Annexin V staining and an increase of poly(ADP-ribose) polymerase
      cleavage. The antiapoptotic protein Mcl-1, a member of the Bcl-2 family, was
      downregulated and correlated with SOID-8 induced apoptosis. In addition, SOID-8
      reduced tyrosine phosphorylation of Signal Tansducer and Activator of
      Transcription 3 (STAT3) in both dose- and time-dependent manners. This inhibition
      was associated with decreased levels of phosphorylation of Janus-activated kinase
      2 (JAK2), an upstream kinase that mediates STAT3 phosphorylation at Tyr705.
      Accordingly, SOID-8 inhibited IL-6-induced activation of STAT3 and JAK2 in
      melanoma cells. Finally, SOID-8 suppressed melanoma tumor growth in a mouse
      xenograft model, accompanied with a decrease of phosphorylation of JAK2 and
      STAT3. Our results indicate that the antitumor activity of SOID-8 is at least
      partially due to inhibition of JAK2/STAT3 signaling in melanoma cells. These
      findings suggest that the spirooxindole derivative SOID-8 is a promising lead
      compound for further development of new preventive and therapeutic agents for
      melanoma.

PMID- 23166635
TI  - Spatial heterogeneity in fishing creates de facto refugia for endangered Celtic
      Sea elasmobranchs.
AB  - The life history characteristics of some elasmobranchs make them particularly
      vulnerable to fishing mortality; about a third of all species are listed by the
      IUCN as Threatened or Near Threatened. Marine Protected Areas (MPAs) have been
      suggested as a tool for conservation of elasmobranchs, but they are likely to be
      effective only if such populations respond to fishing impacts at spatial-scales
      corresponding to MPA size. Using the example of the Celtic Sea, we modelled
      elasmobranch biomass (kg h(-1)) in fisheries-independent survey hauls as a
      function of environmental variables and 'local' (within 20 km radius) fishing
      effort (h y(-1)) recorded from Vessel Monitoring Systems data. Model selection
      using AIC suggested strongest support for linear mixed effects models in which
      the variables (i) fishing effort, (ii) geographic location and (iii) demersal
      fish assemblage had approximately equal importance in explaining elasmobranch
      biomass. In the eastern Celtic Sea, sampling sites that occurred in the lowest
      10% of the observed fishing effort range recorded 10 species of elasmobranch
      including the critically endangered Dipturus spp. The most intensely fished 10%
      of sites had only three elasmobranch species, with two IUCN listed as Least
      Concern. Our results suggest that stable spatial heterogeneity in fishing effort
      creates de facto refugia for elasmobranchs in the Celtic Sea. However, changes in
      the present fisheries management regime could impair the refuge effect by
      changing fisher's behaviour and displacing effort into these areas.

PMID- 23166636
TI  - Polymorphisms in ERCC1 and XPF genes and risk of gastric cancer in an eastern
      Chinese population.
AB  - BACKGROUND: Inherited functional single nucleotide polymorphisms (SNPs) in DNA
      repair genes may alter DNA repair capacity and thus contribute to cancer risk.
      METHODS: Three ERCC1 functional SNPs (rs2298881C>A, rs3212986C>A and rs11615G>A)
      and two XPF/ERCC4 functional SNPs (rs2276466C>G and rs6498486A>C) were genotyped
      for 1125 gastric adenocarcinoma cases and 1196 cancer-free controls by Taqman
      assays. Odds ratios (OR) and 95% confidence intervals (CI) were used to estimate
      risk associations, and false-positive report probabilities (FPRP) were calculated
      for assessing significant findings. RESULTS: ERCC1 rs2298881C and rs11615A
      variant genotypes were associated with increased gastric cancer risk (adjusted
      OR=1.33, 95% CI=1.05-1.67 for rs2298881 AC/CC and adjusted OR=1.23, 95% CI=1.05
      1.46 for rs11615 AG/AA, compared with their common genotype AA and GG,
      respectively). Patients with 2-3 ERCC1 risk genotypes had significant increased
      risk (adjusted OR=1.56, 95% CI=1.27-1.93), compared with those with 0-1 ERCC1
      risk genotypes, and this risk was more significantly in subgroups of never
      drinkers, non-gastric cardia adenocarcinoma (NGCA) and clinical stage I+II. All
      these risks were not observed for XPF SNPs. CONCLUSIONS: These findings suggest
      that functional ERCC1 SNPs may contribute to risk of gastric cancer. Larger and
      well-designed studies with different ethnic populations are needed to validate
      our findings.

PMID- 23166638
TI  - Facial expressions of threat influence perceived gaze direction in 8 year-olds.
AB  - Adults show reciprocal influences between the perception of gaze direction and
      emotional expression. These facilitate the understanding of facial signals,
      because the meaning of one cue can vary considerably depending on the value of
      the other. Here we ask whether children show similar reciprocal influences in the
      perception of gaze and expression. A previous study has demonstrated that gaze
      direction affects the perception of emotional expression in children. Here we
      demonstrate the opposite direction of influence, showing that expression affects
      the perception of gaze direction. Specifically, we show that the cone of gaze,
      i.e., range of gaze deviations perceived as direct, is larger for angry than
      neutral or fearful faces in 8 year-old children. Therefore, we conclude that
      children, like adults, show reciprocal influences in the perception of gaze and
      expression. An unexpected finding was that, compared with adults, children showed
      larger effects of expression on gaze perception. This finding raises the
      possibility that it is the ability to process cues independently, rather than
      sensitivity to combinations, that matures during development. Alternatively,
      children may be particularly sensitive to anger in adult faces.

PMID- 23166639
TI  - Dancing with the tides: fluctuations of coastal phytoplankton orchestrated by
      different oscillatory modes of the tidal cycle.
AB  - Population fluctuations are often driven by an interplay between intrinsic
      population processes and extrinsic environmental forcing. To investigate this
      interplay, we analyzed fluctuations in coastal phytoplankton concentration in
      relation to the tidal cycle. Time series of chlorophyll fluorescence, suspended
      particulate matter (SPM), salinity and temperature were obtained from an
      automated measuring platform in the southern North Sea, covering 9 years of data
      at a resolution of 12 to 30 minutes. Wavelet analysis showed that chlorophyll
      fluctuations were dominated by periodicities of 6 hours 12 min, 12 hours 25 min,
      24 hours and 15 days, which correspond to the typical periodicities of tidal
      current speeds, the semidiurnal tidal cycle, the day-night cycle, and the spring
      neap tidal cycle, respectively. During most of the year, chlorophyll and SPM
      fluctuated in phase with tidal current speed, indicative of alternating periods
      of sinking and vertical mixing of algal cells and SPM driven by the tidal cycle.
      Spring blooms slowly built up over several spring-neap tidal cycles, and
      subsequently expanded in late spring when a strong decline of the SPM
      concentration during neap tide enabled a temporary "escape" of the chlorophyll
      concentration from the tidal mixing regime. Our results demonstrate that the
      tidal cycle is a major determinant of phytoplankton fluctuations at several
      different time scales. These findings imply that high-resolution monitoring
      programs are essential to capture the natural variability of phytoplankton in
      coastal waters.

PMID- 23166637
TI  - A measure of the broad substrate specificity of enzymes based on 'duplicate'
      catalytic residues.
AB  - The ability of an enzyme to select and act upon a specific class of compounds
      with unerring precision and efficiency is an essential feature of life.
      Simultaneously, these enzymes often catalyze the reaction of a range of similar
      substrates of the same class, and also have promiscuous activities on unrelated
      substrates. Previously, we have established a methodology to quantify promiscuous
      activities in a wide range of proteins. In the current work, we quantitatively
      characterize the active site for the ability to catalyze distinct, yet related,
      substrates (BRASS). A protein with known structure and active site residues
      provides the framework for computing 'duplicate' residues, each of which results
      in slightly modified replicas of the active site scaffold. Such spatial
      congruence is supplemented by Finite difference Poisson Boltzmann analysis which
      filters out electrostatically unfavorable configurations. The congruent
      configurations are used to compute an index (BrassIndex), which reflects the
      broad substrate profile of the active site. We identify an acetylhydrolase and a
      methyltransferase as having the lowest and highest BrassIndex, respectively, from
      a set of non-homologous proteins extracted from the Catalytic Site Atlas. The
      acetylhydrolase, a regulatory enzyme, is known to be highly specific for platelet
      activating factor. In the methyltransferase (PDB: 1QAM), various combinations of
      glycine (Gly38/40/42), asparagine (Asn101/11) and glutamic acid (Glu59/36)
      residues having similar spatial and electrostatic profiles with the specified
      scaffold (Gly38, Asn101 and Glu59) exemplifies the broad substrate profile such
      an active site may provide. 'Duplicate' residues identified by relaxing the
      spatial and/or electrostatic constraints can be the target of directed evolution
      methodologies, like saturation mutagenesis, for modulating the substrate
      specificity of proteins.

PMID- 23166640
TI  - The co-chaperone Hch1 regulates Hsp90 function differently than its homologue
      Aha1 and confers sensitivity to yeast to the Hsp90 inhibitor NVP-AUY922.
AB  - Hsp90 is a dimeric ATPase responsible for the activation or maturation of a
      specific set of substrate proteins termed 'clients'. This molecular chaperone
      acts in the context of a structurally dynamic and highly regulated cycle
      involving ATP, co-chaperone proteins and clients. Co-chaperone proteins regulate
      conformational transitions that may be impaired in mutant forms of Hsp90. We
      report here that the in vivo impairment of commonly studied Hsp90 variants
      harbouring the G313S or A587T mutation are exacerbated by the co-chaperone Hch1p.
      Deletion of HCH1, but not AHA1, mitigates the temperature sensitive phenotype and
      high sensitivity to Hsp90 inhibitor drugs observed in Saccharomyces cerevisiae
      that express either of these two Hsp90 variants. Moreover, the deletion of HCH1
      results in high resistance to Hsp90 inhibitors in yeast that express wildtype
      Hsp90. Conversely, the overexpression of Hch1p greatly increases sensitivity to
      Hsp90 inhibition in yeast expressing wildtype Hsp90. We conclude that despite the
      similarity between these two co-chaperones, Hch1p and Aha1p regulate Hsp90
      function in distinct ways and likely independent of their roles as ATPase
      stimulators. We further conclude that Hch1p plays a critical role in regulating
      Hsp90 inhibitor drug sensitivity in yeast.

PMID- 23166641
TI  - Experimental infection of plants with an herbivore-associated bacterial
      endosymbiont influences herbivore host selection behavior.
AB  - Although bacterial endosymbioses are common among phloeophagous herbivores,
      little is known regarding the effects of symbionts on herbivore host selection
      and population dynamics. We tested the hypothesis that plant selection and
      reproductive performance by a phloem-feeding herbivore (potato psyllid,
      Bactericera cockerelli) is mediated by infection of plants with a bacterial
      endosymbiont. We controlled for the effects of herbivory and endosymbiont
      infection by exposing potato plants (Solanum tuberosum) to psyllids infected with
      "Candidatus Liberibacter solanacearum" or to uninfected psyllids. We used these
      treatments as a basis to experimentally test plant volatile emissions, herbivore
      settling and oviposition preferences, and herbivore population growth. Three
      important findings emerged: (1) plant volatile profiles differed with respect to
      both herbivory and herbivory plus endosymbiont infection when compared to
      undamaged control plants; (2) herbivores initially settled on plants exposed to
      endosymbiont-infected psyllids but later defected and oviposited primarily on
      plants exposed only to uninfected psyllids; and (3) plant infection status had
      little effect on herbivore reproduction, though plant flowering was associated
      with a 39% reduction in herbivore density on average. Our experiments support the
      hypothesis that plant infection with endosymbionts alters plant volatile
      profiles, and infected plants initially recruited herbivores but later repelled
      them. Also, our findings suggest that the endosymbiont may not place negative
      selection pressure on its host herbivore in this system, but plant flowering
      phenology appears correlated with psyllid population performance.

PMID- 23166642
TI  - New insights into the ageing of linseed oil paint binder: a qualitative and
      quantitative analytical study.
AB  - This paper presents an analytical investigation of paint reconstructions prepared
      with linseed oil that have undergone typical 19th century treatments in
      preparation for painting. The oil was mechanically extracted from the same seed
      lot, which was then processed by various methods: water washing, heat treatments,
      and the addition of driers, with and without heat. A modern process lead white
      (Dutch source, Schoonhoven) and a commercially available vine black were used as
      pigments. The reconstructions were prepared in 1999, and naturally aged from then
      onwards. We compared thermogravimetric analysis (TG), which yields macromolecular
      information, with gas chromatography-mass spectrometry (GC-MS) and direct
      exposure mass spectrometry (DEMS), which both provide molecular information. The
      study enabled us to quantitatively demonstrate, for the first time, that the
      parameters used to identify drying oils are deeply influenced by the history of
      the paint. In particular, here we show that the ratio between the relative
      amounts of palmitic and stearic acid (P/S), which is used as an index for
      differentiating between drying oils, is extremely dependent on the pigments
      present and the age of the paint. Moreover the study revealed that neither the
      P/S parameter nor the ratios between the relative amounts of the various
      dicarboxylic acids (azelaic over suberic and azelaic over sebacic) can be used to
      trace the sorts of pre-treatment undergone by the oil investigated in this study.
      The final results represent an important milestone for the scientific community
      working in the field, highlighting that further research is still necessary to
      solve the identification of drying oils in works of art.

PMID- 23166643
TI  - Comparative host specificity of human- and pig- associated Staphylococcus aureus
      clonal lineages.
AB  - Bacterial adhesion is a crucial step in colonization of the skin. In this study,
      we investigated the differential adherence to human and pig corneocytes of six
      Staphylococcus aureus strains belonging to three human-associated [ST8 (CC8),
      ST22 (CC22) and ST36(CC30)] and two pig-associated [ST398 (CC398) and
      ST433(CC30)] clonal lineages, and their colonization potential in the pig host
      was assessed by in vivo competition experiments. Corneocytes were collected from
      11 humans and 21 pigs using D-squame(r) adhesive discs, and bacterial adherence
      to corneocytes was quantified by a standardized light microscopy assay. A
      previously described porcine colonization model was used to assess the potential
      of the six strains to colonize the pig host. Three pregnant, S. aureus-free sows
      were inoculated intravaginally shortly before farrowing with different strain
      mixes [mix 1) human and porcine ST398; mix 2) human ST36 and porcine ST433; and
      mix 3) human ST8, ST22, ST36 and porcine ST398] and the ability of individual
      strains to colonize the nasal cavity of newborn piglets was evaluated for 28 days
      after birth by strain-specific antibiotic selective culture. In the corneocyte
      assay, the pig-associated ST433 strain and the human-associated ST22 and ST36
      strains showed significantly greater adhesion to porcine and human corneocytes,
      respectively (p<0.0001). In contrast, ST8 and ST398 did not display preferential
      host binding patterns. In the in vivo competition experiment, ST8 was a better
      colonizer compared to ST22, ST36, and ST433 prevailed over ST36 in colonizing the
      newborn piglets. These results are partly in agreement with previous genetic and
      epidemiological studies indicating the host specificity of ST22, ST36 and ST433
      and the broad-host range of ST398. However, our in vitro and in vivo experiments
      revealed an unexpected ability of ST8 to adhere to porcine corneocytes and
      persist in the nasal cavity of pigs.

PMID- 23166644
TI  - Two adjacent cis-regulatory elements are required for ecdysone response of
      ecdysone receptor (EcR) B1 transcription.
AB  - Three distinct classes of nuclear receptors, EcR, E75, and HR3, are key
      regulators in the ecdysone-inducible gene activation cascade in insects. The
      transcription of these genes is induced by ecdysone (20E) differently, although
      the detailed mechanisms underlying their responses to 20E are largely unknown. We
      identified ecdysone response elements (EcREs) present in the promoters of genes
      coding BmEcR-B1, BmE75-A, and BHR3-B isoforms from Bombyx mori employing
      luciferase reporter assays in an ecdysteroid-responsive cultured cell line, NIAS
      Bm-aff3 (aff3). The EcRE of BmEcR-B1 at -2800 comprises of two adjacent elements
      separated by 5 bp, E1 (15 bp) and E2 (21 bp), both of which are required for the
      20E response. Further analysis using electrophoretic mobility shift assays showed
      that E1 binds to the EcR/USP heterodimer and that E2 may bind to the E-box
      (CACGTG) binding factor such as bHLH protein. The unique E1+E2-type EcRE is also
      detected in the promoter upstream regions of EcR-B1 from seven lepidopteran
      species studied. In contrast, both a 20 bp EcRE identified in the promoter of
      BmE75-A and a 18 bp EcRE identified in the BHR3-B promoter, contained only E1
      type EcR/USP binding element but the E2 type element was not in the promoter
      regions of these genes. The combination of presence of the E2 element or other
      cis-regulatory elements in promoter regions explains the different 20E response
      of each class of nuclear receptor genes. Furthermore, the E1+E2 structure for EcR
      B1 can be involved in a possible cross-talk between ecdysteroid and other
      regulatory pathways.

PMID- 23166645
TI  - Random coil to globular thermal response of a protein (H3.1) with three knowledge
      based coarse-grained potentials.
AB  - The effect of temperature on the conformation of a histone (H3.1) is studied by a
      coarse-grained Monte Carlo simulation based on three knowledge-based contact
      potentials (MJ, BT, BFKV). Despite unique energy and mobility profiles of its
      residues, the histone H3.1 undergoes a systematic (possibly continuous)
      structural transition from a random coil to a globular conformation on reducing
      the temperature. The range over which such a systematic response in variation of
      the radius of gyration (R(g)) with the temperature (T) occurs, however, depends
      on the potential, i.e. DeltaT(MJ) ~ 0.013-0.020, DeltaT(BT) ~ 0.018-0.026, and
      DeltaT(BFKV) ~ 0.006-0.013 (in reduced unit). Unlike MJ and BT potentials,
      results from the BFKV potential show an anomaly where the magnitude of R(g)
      decreases on raising the temperature in a range DeltaT(A) ~ 0.015-0.018 before
      reaching its steady-state random coil configuration. Scaling of the structure
      factor, S(q) ? q(-1/nu), with the wave vector, q=2pi/lambda, and the wavelength,
      lambda, reveals a systematic change in the effective dimension (D(e)~1/nu) of the
      histone with all potentials (MJ, BT, BFKV): D(e)~3 in the globular structure with
      D(e)~2 for the random coil. Reproducibility of the general yet unique (monotonic)
      structural transition of the protein H3.1 with the temperature (in contrast to
      non-monotonic structural response of a similar but different protein H2AX) with
      three interaction sets shows that the knowledge-based contact potential is viable
      tool to investigate structural response of proteins. Caution should be exercise
      with the quantitative comparisons due to differences in transition regimes with
      these interactions.

PMID- 23166646
TI  - The association between intelligence and telomere length: a longitudinal
      population based study.
AB  - Low intelligence has been associated with poor health and mortality, but
      underlying mechanisms remain obscure. We hypothesized that low intelligence is
      associated with accelerated biological ageing as reflected by telomere length; we
      suggested potential mediation of this association by unhealthy behaviors and low
      socioeconomic position. The study was performed in a longitudinal population
      based cohort study of 895 participants (46.8% males). Intelligence was measured
      with the Generalized Aptitude-Test Battery at mean age 52.8 years (33-79 years,
      SD=11.3). Leukocyte telomere length was measured by PCR. Lifestyle and
      socioeconomic factors were assessed using written self-report measures. Linear
      regression analyses, adjusted for age, sex, and telomere length measured at the
      first assessment wave (T1), showed that low intelligence was associated with
      shorter leukocyte telomere length at approximately 2 years follow-up (beta= .081,
      t=2.160, p= .031). Nearly 40% of this association was explained by an unhealthy
      lifestyle, while low socioeconomic position did not add any significant
      mediation. Low intelligence may be a risk factor for accelerated biological
      ageing, thereby providing an explanation for its association with poor health and
      mortality.

PMID- 23166647
TI  - Breast cancer incidence in black and white women stratified by estrogen and
      progesterone receptor statuses.
AB  - BACKGROUND: There is increasing evidence that breast cancer is a heterogeneous
      disease presented by different phenotypes and that white women have a higher
      breast cancer incidence rate, whereas black women have a higher mortality rate.
      It is also well known that white women have lower incidence rates than black
      women until approximately age 40, when rate curves cross over and white women
      have higher rates. The goal of this study was to validate the risk of white and
      black women to breast cancer phenotypes, stratified by statuses of the estrogen
      (ER) and progesterone (PR) receptors. METHODOLOGY/PRINCIPAL FINDINGS: SEER17 data
      were fractioned by receptor status into [ER+, PR+], [ER-, PR-], [ER+, PR-], and
      [ER-, PR+] phenotypes. It was shown that in black women compared to white women,
      cumulative age-specific incidence rates are: (i) smaller for the [ER+, PR+]
      phenotype; (ii) larger for the [ER-, PR-] and [ER-, PR+] phenotypes; and (iii)
      almost equal for the [ER+, PR-] phenotype. Clemmesen's Hook, an undulation unique
      to women's breast cancer age-specific incidence rate curves, is shown here to
      exist in both races only for the [ER+, PR+] phenotype. It was also shown that for
      all phenotypes, rate curves have additional undulations and that age-specific
      incidence rates are nearly proportional in all age intervals.
      CONCLUSIONS/SIGNIFICANCE: For black and white women, risk for the [ER+, PR+], [ER
      , PR-] and [ER-, PR+] phenotypes are race dependent, while risk for the [ER+, PR
      ] phenotype is almost independent of race. The processes of carcinogenesis in
      aging, leading to the development of each of the considered breast cancer
      phenotypes, are similar in these racial groups. Undulations exhibited on the
      curves of age-specific incidence rates of the considered breast cancer phenotypes
      point to the presence of several subtypes (to be determined) of each of these
      phenotypes.

PMID- 23166648
TI  - Neuroimaging during trance state: a contribution to the study of dissociation.
AB  - Despite increasing interest in pathological and non-pathological dissociation,
      few researchers have focused on the spiritual experiences involving dissociative
      states such as mediumship, in which an individual (the medium) claims to be in
      communication with, or under the control of, the mind of a deceased person. Our
      preliminary study investigated psychography - in which allegedly "the spirit
      writes through the medium's hand" - for potential associations with specific
      alterations in cerebral activity. We examined ten healthy psychographers - five
      less expert mediums and five with substantial experience, ranging from 15 to 47
      years of automatic writing and 2 to 18 psychographies per month - using single
      photon emission computed tomography to scan activity as subjects were writing, in
      both dissociative trance and non-trance states. The complexity of the original
      written content they produced was analyzed for each individual and for the sample
      as a whole. The experienced psychographers showed lower levels of activity in the
      left culmen, left hippocampus, left inferior occipital gyrus, left anterior
      cingulate, right superior temporal gyrus and right precentral gyrus during
      psychography compared to their normal (non-trance) writing. The average
      complexity scores for psychographed content were higher than those for control
      writing, for both the whole sample and for experienced mediums. The fact that
      subjects produced complex content in a trance dissociative state suggests they
      were not merely relaxed, and relaxation seems an unlikely explanation for the
      underactivation of brain areas specifically related to the cognitive processing
      being carried out. This finding deserves further investigation both in terms of
      replication and explanatory hypotheses.

PMID- 23166649
TI  - Evaluation of the use of the polyubiquitin genes, Ubi4 and Ubi10 as reference
      genes for expression studies in Brachypodium distachyon.
AB  - BACKGROUND: Brachypodium distachyon is emerging as the model plant for temperate
      grass research and the genome of the community line Bd21 has been sequenced.
      Additionally, techniques have been developed for Agrobacterium-mediated
      transformation for the generation of T-DNA insertional lines. Recently, it was
      reported that expression of the polyubiquitin genes, Ubi4 and Ubi10 are stable in
      different tissues and growth hormone-treated plant samples, leading to the
      conclusion that both Ubi4 and Ubi10 are good reference genes for normalization of
      gene expression data using real-time, quantitative PCR (qPCR). PRINCIPAL
      FINDINGS: Mining of the Joint Genome Institute (JGI) 8X Brachypodium distachyon
      genome assembly showed that Ubi4 and Ubi10 share a high level of sequence
      identity (89%), and in silico analyses of the sequences of Ubi4 (Bradi3g04730)
      and Ubi10 (Bradi1g32860) showed that the primers used previously exhibit multiple
      binding sites within the coding sequences arising from the presence of tandem
      repeats of the coding regions. This can potentially result in over-estimation of
      steady-state levels of Ubi4 and Ubi10. Additionally, due to the high level of
      sequence identity between both genes, primers used previously for amplification
      of Ubi4 can bind to Ubi10 and vice versa, resulting in the formation of non
      specific amplification products. CONCLUSIONS: The results from this study
      indicate that the primers used previously were not sufficiently robust and
      specific. Additionally, their use would result in over-estimation of the steady
      state expression levels of Ubi4. Our results question the validity of using the
      previously proposed primer sets for qPCR amplification of Ubi4 and Ubi10. We
      demonstrate that primers designed to target the 3'-UTRs of Ubi4 and Ubi10 are
      better suited for real-time normalization of steady-state expression levels in
      Brachypodium distachyon.

PMID- 23166650
TI  - The Jak/STAT signaling pathway is downregulated at febrile temperatures.
AB  - BACKGROUND: The Janus family of kinases (JAKs), Jak1, Jak2, Jak3, and Tyk2,
      constitute a subgroup of non-receptor protein tyrosine kinases. Upon cytokine
      binding, the receptor-associated kinases are activated and phosphorylate tyrosine
      residues in their cognate cytokine receptors. Their activities are controlled at
      several levels and include cellular concentration, auto-activation, and
      degradation. PRINCIPAL FINDINGS: Our findings show that elevated temperatures in
      the fever range irreversibly aggregate Jak2 and considerably reduce functional
      Jak2 protein levels. Jak2 synthesis remains unaltered. We observed that also the
      protein level of the signal transducer and activator of transcription, STAT5b, is
      transiently decreased at temperatures above 37 degrees C. Consequently, the
      signaling response, e.g. via the growth hormone receptor, is reduced.
      CONCLUSIONS/SIGNIFICANCE: These findings predict that elevated body temperatures
      lower the responsiveness of cytokine receptors.

PMID- 23166651
TI  - Murine myeloid dendritic cells that phagocytose apoptotic T cells inhibit the
      immune response via NO.
AB  - The contraction phase of antigen-specific immune responses involves the apoptotic
      loss of numerous activated lymphocytes. While apoptotic cells are known to induce
      immune suppression, the mechanisms involved therein are still ambiguous. Some
      reports have speculated that macrophages can induce regulatory T cells (Tregs)
      after engulfing apoptotic cells. In this study, we showed that dendritic cells
      (DCs) that phagocytose apoptotic T cells acquire inhibitory function (named
      DCapos) toward CD4(+) and CD8(+) T cells. These inhibitory DCs could not induce
      the generation of Tregs, but they were found to directly inhibit mDCs that
      initiate CD4(+) and CD8(+) T cell proliferation both in vitro and in vivo.
      Soluble factors including NO play a role in the DCapos-induced suppression of
      CD4(+) and CD8(+) T cell proliferation. Further results showed that STAT3
      phosphorylation and inducible nitric oxide synthase (iNOS) generation were
      enhanced when DCs were co-cultured with apoptotic cells. Both iNOS transcription
      and NO secretion were inhibited in the presence of the specific p-STAT3 inhibitor
      JSI-124. All the data indicated that apoptotic cells could turn DCs to inhibitory
      DCs, which might play important roles in the suppression of immune responses.
      STAT3 activation and the consequent release of NO are responsible for the
      inhibitory functions of DCapos.

PMID- 23166652
TI  - Biomarkers of whale shark health: a metabolomic approach.
AB  - In a search for biomarkers of health in whale sharks and as exploration of
      metabolomics as a modern tool for understanding animal physiology, the metabolite
      composition of serum in six whale sharks (Rhincodon typus) from an aquarium
      collection was explored using (1)H nuclear magnetic resonance (NMR) spectroscopy
      and direct analysis in real time (DART) mass spectrometry (MS). Principal
      components analysis (PCA) of spectral data showed that individual animals could
      be resolved based on the metabolite composition of their serum and that two
      unhealthy individuals could be discriminated from the remaining healthy animals.
      The major difference between healthy and unhealthy individuals was the
      concentration of homarine, here reported for the first time in an elasmobranch,
      which was present at substantially lower concentrations in unhealthy whale
      sharks, suggesting that this metabolite may be a useful biomarker of health
      status in this species. The function(s) of homarine in sharks remain uncertain
      but it likely plays a significant role as an osmolyte. The presence of
      trimethylamine oxide (TMAO), another well-known protective osmolyte of
      elasmobranchs, at 0.1-0.3 mol L(-1) was also confirmed using both NMR and MS.
      Twenty-three additional potential biomarkers were identified based on significant
      differences in the frequency of their occurrence between samples from healthy and
      unhealthy animals, as detected by DART MS. Overall, NMR and MS provided
      complementary data that showed that metabolomics is a useful approach for
      biomarker prospecting in poorly studied species like elasmobranchs.

PMID- 23166653
TI  - Catching what we can't see: manual interception of occluded fly-ball
      trajectories.
AB  - Control of interceptive actions may involve fine interplay between feedback-based
      and predictive mechanisms. These processes rely heavily on target motion
      information available when the target is visible. However, short-term visual
      memory signals as well as implicit knowledge about the environment may also
      contribute to elaborate a predictive representation of the target trajectory,
      especially when visual feedback is partially unavailable because other objects
      occlude the visual target. To determine how different processes and information
      sources are integrated in the control of the interceptive action, we manipulated
      a computer-generated visual environment representing a baseball game. Twenty-four
      subjects intercepted fly-ball trajectories by moving a mouse cursor and by
      indicating the interception with a button press. In two separate sessions, fly
      ball trajectories were either fully visible or occluded for 750, 1000 or 1250 ms
      before ball landing. Natural ball motion was perturbed during the descending
      trajectory with effects of either weightlessness (0 g) or increased gravity (2 g)
      at times such that, for occluded trajectories, 500 ms of perturbed motion were
      visible before ball disappearance. To examine the contribution of previous visual
      experience with the perturbed trajectories to the interception of invisible
      targets, the order of visible and occluded sessions was permuted among subjects.
      Under these experimental conditions, we showed that, with fully visible targets,
      subjects combined servo-control and predictive strategies. Instead, when
      intercepting occluded targets, subjects relied mostly on predictive mechanisms
      based, however, on different type of information depending on previous visual
      experience. In fact, subjects without prior experience of the perturbed
      trajectories showed interceptive errors consistent with predictive estimates of
      the ball trajectory based on a-priori knowledge of gravity. Conversely, the
      interceptive responses of subjects previously exposed to fully visible
      trajectories were compatible with the fact that implicit knowledge of the
      perturbed motion was also taken into account for the extrapolation of occluded
      trajectories.

PMID- 23166654
TI  - The development of a new analytical model for the identification of saccharide
      binders in paint samples.
AB  - This paper describes a method for reliably identifying saccharide materials in
      paintings. Since the 3(rd) millennium B.C., polysaccharide materials such as
      plant gums, sugar, flour, and honey were used as binding media and sizing agents
      in paintings, illuminated manuscripts, and polychrome objects. Although it has
      been reported that plant gums have a stable composition, their identification in
      paint samples is often doubtful and rarely discussed. Our research was carried
      out independently at two different laboratories: the Getty Conservation Institute
      in Los Angeles, USA (GCI) and the Department of Chemistry and Industrial
      Chemistry of the University of Pisa, Italy (DCCI). It was shown in a previous
      stage of this research that the two methods give highly comparable data when
      analysing both reference paint samples and paint layers from art objects, thus
      the combined data was used to build a large database. In this study, the
      simultaneous presence of proteinaceous binders and pigments in fresh and
      artificially aged paint replicas was investigated, and it highlighted how these
      can affect the sugar profile of arabic, tragacanth, and fruit tree gums. The
      environmental contamination due to sugars from various plant tissues is also
      discussed. The results allowed the development of a new model for the reliable
      identification of saccharide binders in paintings based on the evaluation of
      markers that are stable to ageing and unaffected by pigments. This new model was
      applied to the sugar profiles obtained from the analysis of a large number of
      samples from murals, easel paintings, manuscripts, and polychrome objects from
      different geographical areas and dating from the 13(th) century BC to the 20(th)
      century AD, thus demonstrating its reliability.

PMID- 23166655
TI  - Structure of the type III secretion effector protein ExoU in complex with its
      chaperone SpcU.
AB  - Disease causing bacteria often manipulate host cells in a way that facilitates
      the infectious process. Many pathogenic gram-negative bacteria accomplish this by
      using type III secretion systems. In these complex secretion pathways, bacterial
      chaperones direct effector proteins to a needle-like secretion apparatus, which
      then delivers the effector protein into the host cell cytosol. The effector
      protein ExoU and its chaperone SpcU are components of the Pseudomonas aeruginosa
      type III secretion system. Secretion of ExoU has been associated with more severe
      infections in both humans and animal models. Here we describe the 1.92 A X-ray
      structure of the ExoU-SpcU complex, a full-length type III effector in complex
      with its full-length cognate chaperone. Our crystallographic data allow a better
      understanding of the mechanism by which ExoU kills host cells and provides a
      foundation for future studies aimed at designing inhibitors of this potent toxin.

PMID- 23166656
TI  - Comparing habitat suitability and connectivity modeling methods for conserving
      pronghorn migrations.
AB  - Terrestrial long-distance migrations are declining globally: in North America,
      nearly 75% have been lost. Yet there has been limited research comparing habitat
      suitability and connectivity models to identify migration corridors across
      increasingly fragmented landscapes. Here we use pronghorn (Antilocapra americana)
      migrations in prairie habitat to compare two types of models that identify
      habitat suitability: maximum entropy (Maxent) and expert-based (Analytic
      Hierarchy Process). We used distance to wells, distance to water, NDVI, land
      cover, distance to roads, terrain shape and fence presence to parameterize the
      models. We then used the output of these models as cost surfaces to compare two
      common connectivity models, least-cost modeling (LCM) and circuit theory. Using
      pronghorn movement data from spring and fall migrations, we identified potential
      migration corridors by combining each habitat suitability model with each
      connectivity model. The best performing model combination was Maxent with LCM
      corridors across both seasons. Maxent out-performed expert-based habitat
      suitability models for both spring and fall migrations. However, expert-based
      corridors can perform relatively well and are a cost-effective alternative if
      species location data are unavailable. Corridors created using LCM out-performed
      circuit theory, as measured by the number of pronghorn GPS locations present
      within the corridors. We suggest the use of a tiered approach using different
      corridor widths for prioritizing conservation and mitigation actions, such as
      fence removal or conservation easements.

PMID- 23166657
TI  - Working memory-related functional brain patterns in never medicated children with
      ADHD.
AB  - Attention Deficit/Hyperactivity Disorder (ADHD) is a pervasive neurodevelopmental
      disorder characterized by 3 clusters of age-inappropriate cardinal symptoms:
      inattention, hyperactivity and impulsivity. These clinical/behavioural symptoms
      are assumed to result from disturbances within brain systems supporting executive
      functions including working memory (WM), which refers to the ability to
      transiently store and flexibly manipulate task-relevant information. Ongoing or
      past medications, co-morbidity and differences in task performance are potential,
      independent confounds in assessing the integrity of cerebral patterns in ADHD. In
      the present study, we recorded WM-related cerebral activity during a memory
      updating N-back task using functional Magnetic Resonance Imaging (fMRI) in
      control children and never medicated, prepubescent children with ADHD but without
      comorbid symptoms. Despite similar updating performance than controls, children
      with ADHD exhibited decreased, below baseline WM-related activation levels in a
      widespread cortico-subcortical network encompassing bilateral occipital and
      inferior parietal areas, caudate nucleus, cerebellum and functionally connected
      brainstem nuclei. Distinctive functional connectivity patterns were also found in
      the ADHD in these regions, with a tighter coupling in the updating than in the
      control condition with a distributed WM-related cerebral network. Especially,
      cerebellum showed tighter coupling with activity in an area compatible with the
      brainstem red nucleus. These results in children with clinical core symptoms of
      ADHD but without comorbid affections and never treated with medication yield
      evidence for a core functional neuroanatomical network subtending WM-related
      processes in ADHD, which may participate to the pathophysiology and expression of
      clinical symptoms.

PMID- 23166658
TI  - An accessible method for implementing hierarchical models with spatio-temporal
      abundance data.
AB  - A common goal in ecology and wildlife management is to determine the causes of
      variation in population dynamics over long periods of time and across large
      spatial scales. Many assumptions must nevertheless be overcome to make
      appropriate inference about spatio-temporal variation in population dynamics,
      such as autocorrelation among data points, excess zeros, and observation error in
      count data. To address these issues, many scientists and statisticians have
      recommended the use of Bayesian hierarchical models. Unfortunately, hierarchical
      statistical models remain somewhat difficult to use because of the necessary
      quantitative background needed to implement them, or because of the computational
      demands of using Markov Chain Monte Carlo algorithms to estimate parameters.
      Fortunately, new tools have recently been developed that make it more feasible
      for wildlife biologists to fit sophisticated hierarchical Bayesian models (i.e.,
      Integrated Nested Laplace Approximation, 'INLA'). We present a case study using
      two important game species in North America, the lesser and greater scaup, to
      demonstrate how INLA can be used to estimate the parameters in a hierarchical
      model that decouples observation error from process variation, and accounts for
      unknown sources of excess zeros as well as spatial and temporal dependence in the
      data. Ultimately, our goal was to make unbiased inference about spatial variation
      in population trends over time.

PMID- 23166659
TI  - Disentangling the effects of risk factors and clinical care on subnational
      variation in early neonatal mortality in the United States.
AB  - OBJECTIVE: Between 1990 and 2010, the U.S ranking in neonatal mortality slipped
      from 29(th) to 45(th) among countries globally. Substantial subnational variation
      in newborn mortality also exists. Our objective is to measure the extent to which
      trends and subnational variation in early neonatal mortality reflect differences
      in the prevalence of risk factors (gestational age and birth weight) compared to
      differences in clinical care. METHODS: Observational study using linked birth and
      death data for all births in the United States between 1996 and 2006. We examined
      health service area (HSA) level variation in the expected early neonatal
      mortality rate, based on gestational age (GA) and birth-weight (BW), and GA-BW
      adjusted mortality as a proxy for clinical care. We analyzed the relationship
      between selected health system indicators and GA-BW-adjusted mortality. RESULTS:
      The early neonatal death (ENND) rate declined 12% between 1996 and 2006 (2.39 to
      2.10 per 1000 live births). This occurred despite increases in risk factor
      prevalence. There was significant HSA-level variation in the expected ENND rate
      (Rate Ratio: 0.73-1.47) and the GA-BW adjusted rate (Rate ratio: 0.63-1.68).
      Accounting for preterm volume (defined as <34 weeks), the number of neonatologist
      and NICU beds, 25.2% and 58.7% of the HSA-level variance in outcomes was
      explained among all births and very low birth weight babies, respectively.
      CONCLUSION: Improvements in mortality could be realized through the expansion or
      reallocation of clinical neonatal resources, particularly in HSAs with a high
      volume of preterm births; however, prevention of preterm births and low-birth
      weight babies has a greater potential to improve newborn survival in the United
      States.

PMID- 23166661
TI  - Age at adiposity rebound is associated with fat mass in young adult males-the
      GOOD study.
AB  - OBJECTIVE: Age at adiposity rebound (AR) is associated with obesity and Type 2
      Diabetes in adults. The aim of the present study was to investigate the role of
      age at AR in adult fat mass, fat distribution and pubertal timing for a Swedish
      cohort. PATIENTS AND METHODS: This is a retrospective cohort study. Detailed
      growth charts were retrieved for the men participating in the population-based
      GOOD (Gothenburg Osteoporosis and Obesity Determinants) study (n=573). Body
      composition was analysed using dual X-ray absorptiometry and computed tomography
      at 18-20 years of age. Age and BMI at AR were calculated using pediatric growth
      charts and AR was defined as the lowest BMI between 3 and 9 years of age.
      RESULTS: Subjects were divided into early (age at AR below 5.4 years of age),
      middle (age at AR 5.4 to 6.8 years of age) and late (age at AR after 6.8 years of
      age) age at AR tertiles. Subjects in the early age at AR tertile had higher young
      adult BMI (+8%), whole body fat mass (+34%) and amount of subcutaneous adipose
      tissue (+61%) than the subjects in the middle and late tertiles (p<0.01). The
      early age at AR tertile had an increased risk of obesity (Odds Ratio 4.1 [95% CI
      1.2-13.9]) compared with the middle and late tertiles. In addition, the early age
      at AR tertile had Peak Height Velocity (PHV) 7 months earlier than the late
      tertile. CONCLUSIONS: Early age at AR was associated with young adult obesity as
      a consequence of a high amount of subcutaneous adipose tissue in men. In addition
      we made the novel observation that early age at AR was associated with an early
      puberty in men.

PMID- 23166660
TI  - An approach for the identification of targets specific to bone metastasis using
      cancer genes interactome and gene ontology analysis.
AB  - Metastasis is one of the most enigmatic aspects of cancer pathogenesis and is a
      major cause of cancer-associated mortality. Secondary bone cancer (SBC) is a
      complex disease caused by metastasis of tumor cells from their primary site and
      is characterized by intricate interplay of molecular interactions. Identification
      of targets for multifactorial diseases such as SBC, the most frequent
      complication of breast and prostate cancers, is a challenge. Towards achieving
      our aim of identification of targets specific to SBC, we constructed a 'Cancer
      Genes Network', a representative protein interactome of cancer genes. Using graph
      theoretical methods, we obtained a set of key genes that are relevant for generic
      mechanisms of cancers and have a role in biological essentiality. We also
      compiled a curated dataset of 391 SBC genes from published literature which
      serves as a basis of ontological correlates of secondary bone cancer. Building on
      these results, we implement a strategy based on generic cancer genes, SBC genes
      and gene ontology enrichment method, to obtain a set of targets that are specific
      to bone metastasis. Through this study, we present an approach for probing one of
      the major complications in cancers, namely, metastasis. The results on genes that
      play generic roles in cancer phenotype, obtained by network analysis of 'Cancer
      Genes Network', have broader implications in understanding the role of molecular
      regulators in mechanisms of cancers. Specifically, our study provides a set of
      potential targets that are of ontological and regulatory relevance to secondary
      bone cancer.

PMID- 23166662
TI  - Fetal alcohol exposure and IQ at age 8: evidence from a population-based birth
      cohort study.
AB  - BACKGROUND: Observational studies have generated conflicting evidence on the
      effects of moderate maternal alcohol consumption during pregnancy on offspring
      cognition mainly reflecting problems of confounding. Among mothers who drink
      during pregnancy fetal alcohol exposure is influenced not only by mother's intake
      but also by genetic variants carried by both the mother and the fetus.
      Associations between children's cognitive function and both maternal and child
      genotype at these loci can shed light on the effects of maternal alcohol
      consumption on offspring cognitive development. METHODS: We used a large
      population based study of women recruited during pregnancy to determine whether
      genetic variants in alcohol metabolising genes in this cohort of women and their
      children were related to the child's cognitive score (measured by the Weschler
      Intelligence Scale) at age 8. FINDINGS: We found that four genetic variants in
      alcohol metabolising genes in 4167 children were strongly related to lower IQ at
      age 8, as was a risk allele score based on these 4 variants. This effect was only
      seen amongst the offspring of mothers who were moderate drinkers (1-6 units
      alcohol per week during pregnancy (per allele effect estimates were -1.80 (95%
      CI= -2.63 to -0.97) p=0.00002, with no effect among children whose mothers
      abstained during pregnancy (0.16 (95%CI= -1.05 to 1.36) p=0.80), p-value for
      interaction  =0.009). A further genetic variant associated with alcohol
      metabolism in mothers was associated with their child's IQ, but again only among
      mothers who drank during pregnancy.

PMID- 23166663
TI  - Xanthohumol prevents atherosclerosis by reducing arterial cholesterol content via
      CETP and apolipoprotein E in CETP-transgenic mice.
AB  - BACKGROUND: Xanthohumol is expected to be a potent anti-atherosclerotic agent due
      to its inhibition of cholesteryl ester transfer protein (CETP). In this study, we
      hypothesized that xanthohumol prevents atherosclerosis in vivo and used CETP
      transgenic mice (CETP-Tg mice) to evaluate xanthohumol as a functional agent.
      METHODOLOGY/PRINCIPAL FINDINGS: Two strains of mice, CETP-Tg and C57BL/6N (wild
      type), were fed a high cholesterol diet with or without 0.05% (w/w) xanthohumol
      ad libitum for 18 weeks. In CETP-Tg mice, xanthohumol significantly decreased
      accumulated cholesterol in the aortic arch and increased HDL cholesterol (HDL-C)
      when compared to the control group (without xanthohumol). Xanthohumol had no
      significant effect in wild-type mice. CETP activity was significantly decreased
      after xanthohumol addition in CETP-Tg mice compared with the control group and it
      inversely correlated with HDL-C (%) (P<0.05). Furthermore, apolipoprotein E
      (apoE) was enriched in serum and the HDL-fraction in CETP-Tg mice after
      xanthohumol addition, suggesting that xanthohumol ameliorates reverse cholesterol
      transport via apoE-rich HDL resulting from CETP inhibition. CONCLUSIONS: Our
      results suggest xanthohumol prevents cholesterol accumulation in atherogenic
      regions by HDL-C metabolism via CETP inhibition leading to apoE enhancement.

PMID- 23166664
TI  - The crystal structure of Arabidopsis VSP1 reveals the plant class C-like
      phosphatase structure of the DDDD superfamily of phosphohydrolases.
AB  - Arabidopsis thaliana vegetative storage proteins, VSP1 and VSP2, are acid
      phosphatases and belong to the haloacid dehalogenase (HAD) superfamily. In
      addition to their potential nutrient storage function, they were thought to be
      involved in plant defense and flower development. To gain insights into the
      architecture of the protein and obtain clues about its function, we have tested
      their substrate specificity and solved the structure of VSP1. The acid
      phosphatase activities of these two enzymes require divalent metal such as
      magnesium ion. Conversely, the activity of these two enzymes is inhibited by
      vanadate and molybdate, but is resistant to inorganic phosphate. Both VSP1 and
      VSP2 did not exhibit remarkable activities to any physiological substrates
      tested. In the current study, we presented the crystal structure of recombinant
      VSP1 at 1.8 A resolution via the selenomethionine single-wavelength anomalous
      diffraction (SAD). Specifically, an alpha-helical cap domain on the top of the
      alpha/beta core domain is found to be involved in dimerization. In addition,
      despite of the low sequence similarity between VSP1 and other HAD enzymes, the
      core domain of VSP1 containing conserved active site and catalytic machinery
      displays a classic haloacid dehalogenase fold. Furthermore, we found that VSP1 is
      distinguished from bacterial class C acid phosphatase P4 by several structural
      features. To our knowledge, this is the first study to reveal the crystal
      structure of plant vegetative storage proteins.

PMID- 23166665
TI  - The prognostic value of harvested lymph nodes and the metastatic lymph node ratio
      for gastric cancer patients: results of a study of 1,101 patients.
AB  - AIM: To investigate whether the recommendation to remove 15 lymph nodes that is
      used in the staging system is necessary to assess gastric cancer progression and
      to evaluate whether our metastatic lymph node ratio dividing method, adapted from
      the AJCC's (American Joint Committee on Cancer) 7(th) TNM staging system, is
      helpful for the patients with fewer than 15 harvested lymph nodes. METHODS: We
      performed a retrospective study of 1101 patients with histologically diagnosed
      gastric cancer who underwent a D2 gastrectomy at the Sun Yat-sen University
      Cancer Center between January 2001 and December 2010. The Kappa and Chi-squared
      tests were employed to compare the clinicopathological variables. The Kaplan
      Meier method and Cox regression were employed for the univariate and multivariate
      survival analyses. RESULTS: In the trial, 346, 601 and 154 patients had 0-14, 15
      30 and more than 30 lymph nodes harvested, respectively. The median survival
      times of patients with different lymph nodes harvested in N0, N1, N2 and N3a
      groups were 45.43, 54.28 and 66.95 months (p=0.068); 49.22, 44.25 and 56.72
      months (p<0.001), 43.94, 47.97 and 35.19 months (p=0.042); 32.88, 42.76 and 23.50
      months (p=0.016). Dividing the patients who had fewer than 15 lymph nodes
      harvested by the metastatic lymph node ratio at 0, 0.13 and 0.40, the median
      survival times of these 4 groups were 70.6, 50.5, 53.5 and 30.7 months (p<0.001).
      After re-categorising these 4 groups into the N0, N1, N2, N3a groups, the
      histological grade, T staging, premier N staging, and restaged N staging were the
      independent prognostic factors. CONCLUSIONS: Large numbers of lymph nodes
      harvested in radical gastrectomy do not cause stage migration. For those patients
      with a small number of harvested lymph nodes, their stage should be divided by
      the metastatic lymph node ratio, referred to in the TNM staging system, to assign
      them an accurate stage.

PMID- 23166666
TI  - Effective population size dynamics and the demographic collapse of Bornean orang
      utans.
AB  - Bornean orang-utans experienced a major demographic decline and local
      extirpations during the Pleistocene and Holocene due to climate change, the
      arrival of modern humans, of farmers and recent commercially-driven habitat loss
      and fragmentation. The recent loss of habitat and its dramatic fragmentation has
      affected the patterns of genetic variability and differentiation among the
      remaining populations and increased the extinction risk of the most isolated
      ones. However, the contribution of recent demographic events to such genetic
      patterns is still not fully clear. Indeed, it can be difficult to separate the
      effects of recent anthropogenic fragmentation from the genetic signature of
      prehistoric demographic events. Here, we investigated the genetic structure and
      population size dynamics of orang-utans from different sites. Altogether 126
      individuals were analyzed and a full-likelihood Bayesian approach was applied.
      All sites exhibited clear signals of population decline. Population structure is
      known to generate spurious bottleneck signals and we found that it does indeed
      contribute to the signals observed. However, population structure alone does not
      easily explain the observed patterns. The dating of the population decline varied
      across sites but was always within the 200-2000 years period. This suggests that
      in some sites at least, orang-utan populations were affected by demographic
      events that started before the recent anthropogenic effects that occurred in
      Borneo. These results do not mean that the recent forest exploitation did not
      leave its genetic mark on orang-utans but suggests that the genetic pool of orang
      utans is also impacted by more ancient events. While we cannot identify the main
      cause for this decline, our results suggests that the decline may be related to
      the arrival of the first farmers or climatic events, and that more theoretical
      work is needed to understand how multiple demographic events impact the genome of
      species and how we can assess their relative contributions.

PMID- 23166667
TI  - Evaluation of genotype MTBDRsl assay to detect drug resistance associated with
      fluoroquinolones, aminoglycosides and ethambutol on clinical sediments.
AB  - BACKGROUND: The emergence of resistant tuberculosis (TB) is a major setback to
      the global control of the disease as the treatment of such resistance is complex
      and expensive. Use of direct detection of mutations by molecular methods could
      facilitate rapid diagnosis of resistance to offset diagnostic delays. We
      evaluated the performance of the Genotype MTBDRsl (Hain Life Sciences) for the
      detection of second line resistant TB directly from stored smear positive sputum
      sediments. METHODOLOGY/PRINCIPAL FINDINGS: The assay showed a diverse range of
      sensitivity and specificity, 91.26% [95% CI, 84-96] and 95.5% [95% CI, 87-99] for
      FQ (PPV ~97% & NPV ~ 87.67%), 56.19% [95%CI, 46-66] and 81% [95%CI, 66-91] for
      EMB (PPV ~ 88.06% & NPV ~ 43.21%) and 100% for SLD. Diagnostic accuracy for FQ,
      SLD and EMB was 94%, 100% and 63.51%, respectively. 1.17% (2/170) were
      heteroresistance strains, where the heteroresistance was linked to rrs gene. A
      varying rate of validity was observed 100% (170/170) for FQ, 94.11% (160/170) for
      EMB, 88.23% (150/170) for SLD. CONCLUSIONS/SIGNIFICANCE: Genotype MTBDRsl is
      simple, rapid, economical assay that can be used to detect commonly known
      resistance associated with Fluoroquinolone, second line injectable drugs and
      ethambutol. The assay detects the targeted resistance in less time as compared to
      phenotypic DST. But due to low NPV to FQ (88%) and EMB (43.21%), the assay
      results must be interpreted in coordination with the phenotypic DST.

PMID- 23166668
TI  - Case-only designs in pharmacoepidemiology: a systematic review.
AB  - BACKGROUND: Case-only designs have been used since late 1980's. In these, as
      opposed to case-control or cohort studies for instance, only cases are required
      and are self-controlled, eliminating selection biases and confounding related to
      control subjects, and time-invariant characteristics. The objectives of this
      systematic review were to analyze how the two main case-only designs - case
      crossover (CC) and self-controlled case series (SCCS) - have been applied and
      reported in pharmacoepidemiology literature, in terms of applicability
      assumptions and specificities of these designs. METHODOLOGY/PRINCIPAL FINDINGS:
      We systematically selected all reports in this field involving case-only designs
      from MEDLINE and EMBASE up to September 15, 2010. Data were extracted using a
      standardized form. The analysis included 93 reports 50 (54%) of CC and 45 (48%)
      SCCS, 2 reports combined both designs. In 12 (24%) CC and 18 (40%) SCCS articles,
      all applicable validity assumptions of the designs were fulfilled, respectively.
      Fifty (54%) articles (15 CC (30%) and 35 (78%) SCCS) adequately addressed the
      specificities of the case-only analyses in the way they reported results.
      CONCLUSIONS/SIGNIFICANCE: Our systematic review underlines that implementation of
      CC and SCCS designs needs to be more rigorous with regard to validity
      assumptions, as well as improvement in results reporting.

PMID- 23166669
TI  - Finite adaptation and multistep moves in the metropolis-hastings algorithm for
      variable selection in genome-wide association analysis.
AB  - High-dimensional datasets with large amounts of redundant information are
      nowadays available for hypothesis-free exploration of scientific questions. A
      particular case is genome-wide association analysis, where variations in the
      genome are searched for effects on disease or other traits. Bayesian variable
      selection has been demonstrated as a possible analysis approach, which can
      account for the multifactorial nature of the genetic effects in a linear
      regression model.Yet, the computation presents a challenge and application to
      large-scale data is not routine. Here, we study aspects of the computation using
      the Metropolis-Hastings algorithm for the variable selection: finite adaptation
      of the proposal distributions, multistep moves for changing the inclusion state
      of multiple variables in a single proposal and multistep move size adaptation. We
      also experiment with a delayed rejection step for the multistep moves. Results on
      simulated and real data show increase in the sampling efficiency. We also
      demonstrate that with application specific proposals, the approach can overcome a
      specific mixing problem in real data with 3822 individuals and 1,051,811 single
      nucleotide polymorphisms and uncover a variant pair with synergistic effect on
      the studied trait. Moreover, we illustrate multimodality in the real dataset
      related to a restrictive prior distribution on the genetic effect sizes and
      advocate a more flexible alternative.

PMID- 23166670
TI  - Human umbilical cord blood-derived mesenchymal stem cells promote vascular growth
      in vivo.
AB  - Stem cell therapies are promising strategies to regenerate human injured tissues,
      including ischemic myocardium. Here, we examined the acquisition of properties
      associated with vascular growth by human umbilical cord blood-derived mesenchymal
      stem cells (UCBMSCs), and whether they promoted vascular growth in vivo. UCBMSCs
      were induced in endothelial cell-specific growth medium (EGM-2) acquiring new
      cell markers, increased Ac-LDL uptake, and migratory capacity as assessed by qRT
      PCR, Western blotting, indirect immunofluorescence, and invasion assays.
      Angiogenic and vasculogenic potentials could be anticipated by in vitro
      experiments showing self organization into Matrigel-mediated cell networks, and
      activation of circulating angiogenic-supportive myeloid cells. In mice, following
      subcutaneous co-injection with Matrigel, UCBMSCs modified to co-express
      bioluminescent (luciferases) and fluorescent proteins were demonstrated to
      participate in the formation of new microvasculature connected with the host
      circulatory system. Response of UCBMSCs to ischemia was explored in a mouse model
      of acute myocardial infarction (MI). UCBMSCs transplanted using a fibrin patch
      survived 4 weeks post-implantation and organized into CD31(+)network structures
      above the infarcted myocardium. MI-treated animals showed a reduced infarct scar
      and a larger vessel-occupied area in comparison with MI-control animals. Taken
      together, the presented results show that UCBMSCs can be induced in vitro to
      acquire angiogenic and vasculogenic properties and contribute to vascular growth
      in vivo.

PMID- 23166671
TI  - Discovery of a novel polyomavirus in acute diarrheal samples from children.
AB  - Polyomaviruses are small circular DNA viruses associated with chronic infections
      and tumors in both human and animal hosts. Using an unbiased deep sequencing
      approach, we identified a novel, highly divergent polyomavirus, provisionally
      named MX polyomavirus (MXPyV), in stool samples from children. The ~5.0 kB viral
      genome exhibits little overall homology (<46% amino acid identity) to known
      polyomaviruses, and, due to phylogenetic variation among its individual proteins,
      cannot be placed in any existing taxonomic group. PCR-based screening detected
      MXPyV in 28 of 834 (3.4%) fecal samples collected from California, Mexico, and
      Chile, and 1 of 136 (0.74%) of respiratory samples from Mexico, but not in blood
      or urine samples from immunocompromised patients. By quantitative PCR, the
      measured titers of MXPyV in human stool at 10% (weight/volume) were as high as
      15,075 copies. No association was found between the presence of MXPyV and
      diarrhea, although girls were more likely to shed MXPyV in the stool than boys
      (p=0.012). In one child, viral shedding was observed in two stools obtained 91
      days apart, raising the possibility of chronic infection by MXPyV. A multiple
      sequence alignment revealed that MXPyV is a closely related variant of the
      recently reported MWPyV and HPyV10 polyomaviruses. Further studies will be
      important to determine the association, if any, of MXPyV with disease in humans.

PMID- 23166672
TI  - Human BAT possesses molecular signatures that resemble beige/brite cells.
AB  - Brown adipose tissue (BAT) dissipates chemical energy and generates heat to
      protect animals from cold and obesity. Rodents possess two types of UCP-1
      positive brown adipocytes arising from distinct developmental lineages:
      "classical" brown adipocytes develop during the prenatal stage whereas "beige" or
      "brite" cells that reside in white adipose tissue (WAT) develop during the
      postnatal stage in response to chronic cold or PPARgamma agonists. Beige cells'
      inducible characteristics make them a promising therapeutic target for obesity
      treatment, however, the relevance of this cell type in humans remains unknown. In
      the present study, we determined the gene signatures that were unique to
      classical brown adipocytes and to beige cells induced by a specific PPARgamma
      agonist rosiglitazone in mice. Subsequently we applied the transcriptional data
      to humans and examined the molecular signatures of human BAT isolated from
      multiple adipose depots. To our surprise, nearly all the human BAT abundantly
      expressed beige cell-selective genes, but the expression of classical brown fat
      selective genes were nearly undetectable. Interestingly, expression of known
      brown fat-selective genes such as PRDM16 was strongly correlated with that of the
      newly identified beige cell-selective genes, but not with that of classical brown
      fat-selective genes. Furthermore, histological analyses showed that a new beige
      cell marker, CITED1, was selectively expressed in the UCP1-positive beige cells
      as well as in human BAT. These data indicate that human BAT may be primary
      composed of beige/brite cells.

PMID- 23166673
TI  - Multiple novel alternative splicing forms of FBXW7alpha have a translational
      modulatory function and show specific alteration in human cancer.
AB  - FBXW7 acts as a tumor suppressor through ubiquitination and degradation of
      multiple oncoproteins. Loss of FBXW7 expression, which could be partially
      attributed by the genomic deletion or mutation of FBXW7 locus, is frequently
      observed in various human cancers. However, the mechanisms regulating FBXW7
      expression still remain poorly understood. Here we examined the 5' region of
      FBXW7 gene to investigate the regulation of FBXW7 expression. We identified seven
      alternative splicing (AS) 5'-UTR forms of FBXW7alpha that are composed of
      multiple novel non-coding exons. A significant difference in translational
      efficiency among these 5'-UTRs variants was observed by in vivo Luciferase
      reporter assay and Western blot. Furthermore, we found that the mRNA level of the
      AS form with high translational efficiency was specifically reduced in more than
      80% of breast cancer cell lines and in more than 50% of human primary cancers
      from various tissues. In addition, we also identified mutations of FBXW7 in
      prostate cancers (5.6%), kidney cancers (16.7%), and bladder cancers (18.8%). Our
      results suggest that in addition to mutation, differential expression of
      FBXW7alpha AS forms with different translational properties may serve as a novel
      mechanism for inactivation of FBXW7 in human cancer.

PMID- 23166674
TI  - Probability of seeing increases saccadic readiness.
AB  - Associating movement directions or endpoints with monetary rewards or costs
      influences movement parameters in humans, and associating movement directions or
      endpoints with food reward influences movement parameters in non-human primates.
      Rewarded movements are facilitated relative to non-rewarded movements. The
      present study examined to what extent successful foveation facilitated saccadic
      eye movement behavior, with the hypothesis that foveation may constitute an
      informational reward. Human adults performed saccades to peripheral targets that
      either remained visible after saccade completion or were extinguished, preventing
      visual feedback. Saccades to targets that were systematically extinguished were
      slower and easier to inhibit than saccades to targets that afforded successful
      foveation, and this effect was modulated by the probability of successful
      foveation. These results suggest that successful foveation facilitates behavior,
      and that obtaining the expected sensory consequences of a saccadic eye movement
      may serve as a reward for the oculomotor system.

PMID- 23166676
TI  - High affinity humanized antibodies without making hybridomas; immunization paired
      with mammalian cell display and in vitro somatic hypermutation.
AB  - A method has been developed for the rapid generation of high-affinity humanized
      antibodies from immunized animals without the need to make conventional
      hybridomas. Rearranged IgH D(J) regions were amplified from the spleen and lymph
      tissue of mice immunized with the human complement protein C5, fused with a
      limited repertoire of human germline heavy chain V-genes to form intact humanized
      heavy chains, and paired with a human light chain library. Completed heavy and
      light chains were assembled for mammalian cell surface display and transfected
      into HEK 293 cells co-expressing activation-induced cytidine deaminase (AID).
      Numerous clones were isolated by fluorescence-activated cell sorting, and
      affinity maturation, initiated by AID, resulted in the rapid evolution of high
      affinity, functional antibodies. This approach enables the efficient sampling of
      an immune repertoire and the direct selection and maturation of high-affinity,
      humanized IgGs.

PMID- 23166675
TI  - Comparative analysis of genome sequences covering the seven cronobacter species.
AB  - BACKGROUND: Species of Cronobacter are widespread in the environment and are
      occasional food-borne pathogens associated with serious neonatal diseases,
      including bacteraemia, meningitis, and necrotising enterocolitis. The genus is
      composed of seven species: C. sakazakii, C. malonaticus, C. turicensis, C.
      dublinensis, C. muytjensii, C. universalis, and C. condimenti. Clinical cases are
      associated with three species, C. malonaticus, C. turicensis and, in particular,
      with C. sakazakii multilocus sequence type 4. Thus, it is plausible that
      virulence determinants have evolved in certain lineages. METHODOLOGY/PRINCIPAL
      FINDINGS: We generated high quality sequence drafts for eleven Cronobacter
      genomes representing the seven Cronobacter species, including an ST4 strain of C.
      sakazakii. Comparative analysis of these genomes together with the two publicly
      available genomes revealed Cronobacter has over 6,000 genes in one or more
      strains and over 2,000 genes shared by all Cronobacter. Considerable variation in
      the presence of traits such as type six secretion systems, metal resistance
      (tellurite, copper and silver), and adhesins were found. C. sakazakii is unique
      in the Cronobacter genus in encoding genes enabling the utilization of exogenous
      sialic acid which may have clinical significance. The C. sakazakii ST4 strain 701
      contained additional genes as compared to other C. sakazakii but none of them
      were known specific virulence-related genes. CONCLUSIONS/SIGNIFICANCE: Genome
      comparison revealed that pair-wise DNA sequence identity varies between 89 and
      97% in the seven Cronobacter species, and also suggested various degrees of
      divergence. Sets of universal core genes and accessory genes unique to each
      strain were identified. These gene sequences can be used for designing
      genus/species specific detection assays. Genes encoding adhesins, T6SS, and metal
      resistance genes as well as prophages are found in only subsets of genomes and
      have contributed considerably to the variation of genomic content. Differences in
      gene content likely contribute to differences in the clinical and environmental
      distribution of species and sequence types.

PMID- 23166677
TI  - Identification of novel and differentially expressed MicroRNAs of dairy goat
      mammary gland tissues using solexa sequencing and bioinformatics.
AB  - MicroRNAs are small, noncoding RNA molecules that regulate gene expression at the
      post-transcriptional level and play an important role in various biological
      processes. Although most microRNAs expression profiles studies have been
      performed in humans or rodents, relatively limited knowledge also exists in other
      mammalian species. The identification of the full repertoire of microRNAs
      expressed in the lactating mammary gland of Capra hircus would significantly
      increase our understanding of the physiology of lactating mammary glands. In this
      study, two libraries were constructed using the lactating mammary gland tissues
      of Laoshan dairy goats (Capra hircus) during peak and late lactation. Solexa high
      throughput sequencing technique and bioinformatics were used to determine the
      abundance and differential expression of the microRNAs between peak and late
      lactation. As a result, 19,044,002 and 7,385,833 clean reads were obtained,
      respectively, and 1,113 conserved known microRNAs and 31 potential novel microRNA
      candidates were identified. A total of 697 conserved microRNAs were significantly
      differentially expressed with a P-value<0.01, 272 microRNAs were up-regulated and
      425 microRNAs were down-regulated during peak lactation. The results were
      validated using real-time quantitative RT-PCR. 762,557 annotated mRNA transcripts
      were predicted as putative target gene candidates. The GO annotation and KEGG
      pathway analysis suggested that differentially expressed microRNAs were involved
      in mammary gland physiology, including signal transduction, and cell-cell and
      cell-extracellular communications. This study provided the first global of the
      microRNA in Capra hircus and expanded the repertoire of microRNAs. Our results
      have great significance and value for the elucidation of complex regulatory
      networks between microRNAs and mRNAs and for the study of mammary gland
      physiology and lactation.

PMID- 23166678
TI  - Somatic mutations of PIK3R1 promote gliomagenesis.
AB  - The phosphoinositide 3-kinase (PI3K) pathway is targeted for frequent alteration
      in glioblastoma (GBM) and is one of the core GBM pathways defined by The Cancer
      Genome Atlas. Somatic mutations of PIK3R1 are observed in multiple tumor types,
      but the tumorigenic activity of these mutations has not been demonstrated in GBM.
      We show here that somatic mutations in the iSH2 domain of PIK3R1 act as oncogenic
      driver events. Specifically, introduction of a subset of the mutations identified
      in human GBM, in the nSH2 and iSH2 domains, increases signaling through the PI3K
      pathway and promotes tumorigenesis of primary normal human astrocytes in an
      orthotopic xenograft model. Furthermore, we show that cells that are dependent on
      mutant P85alpha-mediated PI3K signaling exhibit increased sensitivity to a small
      molecule inhibitor of AKT. Together, these results suggest that GBM patients
      whose tumors carry mutant PIK3R1 alleles may benefit from treatment with
      inhibitors of AKT.

PMID- 23166679
TI  - Efficient derivation of multipotent neural stem/progenitor cells from non-human
      primate embryonic stem cells.
AB  - The common marmoset (Callithrix jacchus) is a small New World primate that has
      been used as a non-human primate model for various biomedical studies. We
      previously demonstrated that transplantation of neural stem/progenitor cells
      (NS/PCs) derived from mouse and human embryonic stem cells (ESCs) and induced
      pluripotent stem cells (iPSCs) promote functional locomotor recovery of mouse
      spinal cord injury models. However, for the clinical application of such a
      therapeutic approach, we need to evaluate the efficacy and safety of pluripotent
      stem cell-derived NS/PCs not only by xenotransplantation, but also
      allotransplantation using non-human primate models to assess immunological
      rejection and tumorigenicity. In the present study, we established a culture
      method to efficiently derive NS/PCs as neurospheres from common marmoset ESCs.
      Marmoset ESC-derived neurospheres could be passaged repeatedly and showed
      sequential generation of neurons and astrocytes, similar to that of mouse ESC
      derived NS/PCs, and gave rise to functional neurons as indicated by calcium
      imaging. Although marmoset ESC-derived NS/PCs could not differentiate into
      oligodendrocytes under default culture conditions, these cells could abundantly
      generate oligodendrocytes by incorporating additional signals that recapitulate
      in vivo neural development. Moreover, principal component analysis of microarray
      data demonstrated that marmoset ESC-derived NS/PCs acquired similar gene
      expression profiles to those of fetal brain-derived NS/PCs by repeated passaging.
      Therefore, marmoset ESC-derived NS/PCs may be useful not only for accurate
      evaluation by allotransplantation of NS/PCs into non-human primate models, but
      are also applicable to analysis of iPSCs established from transgenic disease
      model marmosets.

PMID- 23166680
TI  - Impaired olfactory associative behavior of honeybee workers due to contamination
      of imidacloprid in the larval stage.
AB  - The residue of imidacloprid in the nectar and pollens of the plants is toxic not
      only to adult honeybees but also the larvae. Our understanding of the risk of
      imidacloprid to larvae of the honeybees is still in a very early stage. In this
      study, the capped-brood, pupation and eclosion rates of the honeybee larvae were
      recorded after treating them directly in the hive with different dosages of
      imidacloprid. The brood-capped rates of the larvae decreased significantly when
      the dosages increased from 24 to 8000 ng/larva. However, there were no
      significant effects of DMSO or 0.4 ng of imidacloprid per larva on the brood
      capped, pupation and eclosion rates. Although the sublethal dosage of
      imidacloprid had no effect on the eclosion rate, we found that the olfactory
      associative behavior of the adult bees was impaired if they had been treated with
      0.04 ng/larva imidacloprid in the larval stage. These results demonstrate that a
      sublethal dosage of imidacloprid given to the larvae affects the subsequent
      associative ability of the adult honeybee workers. Thus, a low dose of
      imidacloprid may affect the survival condition of the entire colony, even though
      the larvae survive to adulthood.

PMID- 23166681
TI  - Validation of orthopedic postoperative pain assessment methods for dogs: a
      prospective, blinded, randomized, placebo-controlled study.
AB  - In the context of translational research, there is growing interest in studying
      surgical orthopedic pain management approaches that are common to humans and
      dogs. The validity of postoperative pain assessment methods is uncertain with
      regards to responsiveness and the potential interference of analgesia. The
      hypothesis was that video analysis (as a reference), electrodermal activity, and
      two subjective pain scales (VAS and 4A-VET) would detect different levels of pain
      intensity in dogs after a standardized trochleoplasty procedure. In this
      prospective, blinded, randomized study, postoperative pain was assessed in 25
      healthy dogs during a 48-hour time frame (T). Pain was managed with placebo
      (Group 1, n = 10), preemptive and multimodal analgesia (Group 2, n = 5), or
      preemptive analgesia consisting in oral tramadol (Group 3, n = 10). Changes over
      time among groups were analyzed using generalized estimating equations.
      Multivariate regression tested the significance of relationships between pain
      scales and video analysis. Video analysis identified that one orthopedic
      behavior, namely 'Walking with full weight bearing' of the operated leg,
      decreased more in Group 1 at T24 (indicative of pain), whereas three behaviors
      indicative of sedation decreased in Group 2 at T24 (all p<0.004). Electrodermal
      activity was higher in Group 1 than in Groups 2 and 3 until T1 (p<0.0003). The
      VAS was not responsive. 4A-VET showed divergent results as its orthopedic
      component (4A-VETleg) detected lower pain in Group 2 until T12 (p<0.0009), but
      its interactive component (4A-VETbeh) was increased in Group 2 from T12 to T48
      (p<0.001). Concurrent validity established that 4A-VETleg scores the painful
      orthopedic condition accurately and that pain assessment through 4A-VETbeh and
      VAS was severely biased by the sedative side-effect of the analgesics. Finally,
      the video analysis offered a concise template for assessment in dogs with acute
      orthopedic pain. However, subjective pain quantification methods and
      electrodermal activity need further investigation.

PMID- 23166682
TI  - Reproductive number and serial interval of the first wave of influenza
      A(H1N1)pdm09 virus in South Africa.
AB  - BACKGROUND/OBJECTIVE: Describing transmissibility parameters of past pandemics
      from diverse geographic sites remains critical to planning responses to future
      outbreaks. We characterize the transmissibility of influenza A(H1N1)pdm09
      (hereafter pH1N1) in South Africa during 2009 by estimating the serial interval
      (SI), the initial effective reproductive number (initial R(t)) and the temporal
      variation of R(t). METHODS: We make use of data from a central registry of all
      pH1N1 laboratory-confirmed cases detected throughout South Africa. Whenever date
      of symptom onset is missing, we estimate it from the date of specimen collection
      using a multiple imputation approach repeated 100 times for each missing value.
      We apply a likelihood-based method (method 1) for simultaneous estimation of
      initial R(t) and the SI; estimate initial R(t) from SI distributions established
      from prior field studies (method 2); and the Wallinga and Teunis method (method
      3) to model the temporal variation of R(t). RESULTS: 12,360 confirmed pH1N1 cases
      were reported in the central registry. During the period of exponential growth of
      the epidemic (June 21 to August 3, 2009), we simultaneously estimate a mean R(t)
      of 1.47 (95% CI: 1.30-1.72) and mean SI of 2.78 days (95% CI: 1.80-3.75) (method
      1). Field studies found a mean SI of 2.3 days between primary cases and
      laboratory-confirmed secondary cases, and 2.7 days when considering both
      suspected and confirmed secondary cases. Incorporating the SI estimate from field
      studies using laboratory-confirmed cases, we found an initial R(t) of 1.43 (95%
      CI: 1.38-1.49) (method 2). The mean R(t) peaked at 2.91 (95% CI: 0.85-2.91) on
      June 21, as the epidemic commenced, and R(t)>1 was sustained until August 22
      (method 3). CONCLUSIONS: Transmissibility characteristics of pH1N1 in South
      Africa are similar to estimates reported by countries outside of Africa.
      Estimations using the likelihood-based method are in agreement with field
      findings.

PMID- 23166683
TI  - Beat-to-beat vectorcardiographic analysis of ventricular depolarization and
      repolarization in myocardial infarction.
AB  - OBJECTIVES: Increased beat-to-beat variability in the QT interval has been
      associated with heart disease and mortality. The purpose of this study was to
      investigate the beat-to-beat spatial and temporal variations of ventricular
      depolarization and repolarization in vectorcardiogram (VCG) for characterising
      myocardial infarction (MI) patients. METHODS: Standard 12-lead ECGs of 84 MI
      patients (22 f, 63+/-12 yrs; 62 m, 56+/-10 yrs) and 69 healthy subjects (17 f,
      42+/-18 yrs; 52 m, 40+/-13 yrs) were investigated. To extract the beat-to-beat QT
      intervals, a template-matching algorithm and the singular value decomposition
      method have been applied to synthesise the ECG data to VCG. Spatial and temporal
      variations in the QRS complex and T-wave loops were studied by investigating
      several descriptors (point-to-point distance variability, mean loop length, T
      wave morphology dispersion, percentage of loop area, total cosine R-to-T).
      RESULTS: Point-to-point distance variability of QRS and T-loops (0.13+/-0.04 vs.
      0.10+/-0.04, p< 0.0001 and 0.16+/-0.07 vs. 0.13+/-0.06, p< 0.05) were
      significantly larger in the MI group than in the control group. The average T
      wave morphology dispersion was significantly higher in the MI group than in the
      control group (62 degrees +/-8 degrees  vs. 38 degrees +/-16 degrees , p<
      0.0001). Further, its beat-to-beat variability appeared significantly lower in
      the MI group than in the control group (12 degrees +/-5 degrees  vs. 15 degrees
      +/-6 degrees , p< 0.005). Moreover, the average percentage of the T-loop area was
      found significantly lower in the MI group than the controls (46+/-17 vs. 55+/-15,
      p< 0.001). Finally, the average and beat-to-beat variability of total cosine R-to
      T were not found statistically significant between both groups. CONCLUSIONS: Beat
      to-beat assessment of VCG parameters may have diagnostic attributes that might
      help in identifying MI patients.

PMID- 23166684
TI  - Genetic characterization of smg-8 mutants reveals no role in C. elegans nonsense
      mediated decay.
AB  - The nonsense mediated decay (NMD) pathway degrades mRNAs bearing premature
      translation termination codons. In mammals, SMG-8 has been implicated in the NMD
      pathway, in part by its association with SMG-1 kinase. Here we use four
      independent assays to show that C. elegans smg-8 is not required to degrade
      nonsense-containing mRNAs. We examine the genetic requirement for smg-8 to
      destabilize the endogenous, natural NMD targets produced by alternative splicing
      of rpl-7a and rpl-12. We test smg-8 for degradation of the endogenous, NMD target
      generated by unc-54(r293), which lacks a normal polyadenylation site. We probe
      the effect of smg-8 on the exogenous NMD target produced by myo-3::GFP, which
      carries a long 3' untranslated region that destabilizes mRNAs. None of these
      known NMD targets is influenced by smg-8 mutations. In addition, smg-8 animals
      lack classical Smg mutant phenotypes such as a reduced brood size or abnormal
      vulva. We conclude that smg-8 is unlikely to encode a component critical for NMD.

PMID- 23166685
TI  - Protection against West Nile virus infection in mice after inoculation with type
      I interferon-inducing RNA transcripts.
AB  - West Nile virus (WNV) is a neurovirulent single stranded RNA mosquito-borne
      flavivirus, whose main natural hosts are birds, but it also infects humans and
      horses. Nowadays, no human vaccine is commercially available and clinical
      treatment is only supportive. Recently, it has been shown that RNA transcripts,
      mimicking structural domains in the non-coding regions (NCRs) of the foot-and
      mouth disease virus (FMDV) induce a potent IFN response and antiviral activity in
      transfected cultured cells, and also reduced mice susceptibility to FMDV. By
      using different transcripts combinations, administration schedules, and infecting
      routes and doses, we have demonstrated that these FMDV RNA transcripts protect
      suckling and adult mice against lethal challenge with WNV. The protective
      activity induced by the transcripts was systemic and dependent on the infection
      route and dose. These results confirm the antiviral potential of these synthetic
      RNAs for fighting viruses of different families relevant for human and animal
      health.

PMID- 23166686
TI  - The FgHOG1 pathway regulates hyphal growth, stress responses, and plant infection
      in Fusarium graminearum.
AB  - Fusarium head blight (FHB) caused by Fusarium graminearum is a destructive
      disease of wheat and barley worldwide. In a previous study of systematic
      characterization of protein kinase genes in F. graminearum, mutants of three
      putative components of the osmoregulation MAP kinase pathway were found to have
      distinct colony morphology and hyphal growth defects on PDA plates. Because the
      osmoregulation pathway is not known to regulate aerial hyphal growth and
      branching, in this study we further characterized the functions of the FgHog1
      pathway in growth, pathogenesis, and development. The Fghog1, Fgpbs2, and Fgssk2
      mutants were all reduced in growth rate, aerial hyphal growth, and hyphal
      branching angle. These mutants were not only hypersensitive to osmotic stress but
      also had increased sensitivity to oxidative, cytoplasm membrane, and cell wall
      stresses. The activation of FgHog1 was blocked in the Fgpbs2 and Fgssk2 mutants,
      indicating the sequential activation of FgSsk2-FgPbs2-FgHog1 cascade.
      Interestingly, the FgHog1 MAPK pathway mutants appeared to be sensitive to
      certain compounds present in PDA. They were female sterile but retained male
      fertility. We also used the metabolomics profiling approach to identify
      compatible solutes that were accumulated in the wild type but not in the Fghog1
      deletion mutant. Overall, our results indicate that the FgSsk2-FgPbs2-FgHog1 MAPK
      cascade is important for regulating hyphal growth, branching, plant infection,
      and hyperosmotic and general stress responses in F. graminearum.

PMID- 23166688
TI  - MHD free convective boundary layer flow of a nanofluid past a flat vertical plate
      with Newtonian heating boundary condition.
AB  - Steady two dimensional MHD laminar free convective boundary layer flows of an
      electrically conducting Newtonian nanofluid over a solid stationary vertical
      plate in a quiescent fluid taking into account the Newtonian heating boundary
      condition is investigated numerically. A magnetic field can be used to control
      the motion of an electrically conducting fluid in micro/nano scale systems used
      for transportation of fluid. The transport equations along with the boundary
      conditions are first converted into dimensionless form and then using linear
      group of transformations, the similarity governing equations are developed. The
      transformed equations are solved numerically using the Runge-Kutta-Fehlberg
      fourth-fifth order method with shooting technique. The effects of different
      controlling parameters, namely, Lewis number, Prandtl number, buoyancy ratio,
      thermophoresis, Brownian motion, magnetic field and Newtonian heating on the flow
      and heat transfer are investigated. The numerical results for the dimensionless
      axial velocity, temperature and nanoparticle volume fraction as well as the
      reduced Nusselt and Sherwood number have been presented graphically and
      discussed. It is found that the rate of heat and mass transfer increase as
      Newtonian heating parameter increases. The dimensionless velocity and temperature
      distributions increase with the increase of Newtonian heating parameter. The
      results of the reduced heat transfer rate is compared for convective heating
      boundary condition and found an excellent agreement.

PMID- 23166687
TI  - The rs1024611 regulatory region polymorphism is associated with CCL2 allelic
      expression imbalance.
AB  - CC chemokine ligand 2 (CCL2) is the most potent monocyte chemoattractant and
      inter-individual differences in its expression level have been associated with
      genetic variants mapping to the cis-regulatory regions of the gene. An A to G
      polymorphism in the CCL2 enhancer region at position -2578 (rs1024611; A>G), was
      found in most studies to be associated with higher serum CCL2 levels and
      increased susceptibility to a variety of diseases such as HIV-1 associated
      neurological disorders, tuberculosis, and atherosclerosis. However, the precise
      mechanism by which rs1024611influences CCL2 expression is not known. To address
      this knowledge gap, we tested the hypothesis that rs1024611G polymorphism is
      associated with allelic expression imbalance (AEI) of CCL2. We used haplotype
      analysis and identified a transcribed SNP in the 3'UTR (rs13900; C>T) can serve
      as a proxy for the rs1024611 and demonstrated that the rs1024611G allele
      displayed a perfect linkage disequilibrium with rs13900T allele. Allele-specific
      transcript quantification in lipopolysaccharide treated PBMCs obtained from
      heterozygous donors showed that rs13900T allele were expressed at higher levels
      when compared to rs13900C allele in all the donors examined suggesting that CCL2
      is subjected to AEI and that that the allele containing rs1024611G is
      preferentially transcribed. We also found that AEI of CCL2 is a stable trait and
      could be detected in newly synthesized RNA. In contrast to these in vivo
      findings, in vitro assays with haplotype-specific reporter constructs indicated
      that the haplotype bearing rs1024611G had a lower or similar transcriptional
      activity when compared to the haplotype containing rs1024611A. This discordance
      between the in vivo and in vitro expression studies suggests that the CCL2
      regulatory region polymorphisms may be functioning in a complex and context
      dependent manner. In summary, our studies provide strong functional evidence and
      a rational explanation for the phenotypic effects of the CCL2 rs1024611G allele.

PMID- 23166689
TI  - Stain-free quantification of chromosomes in live cells using regularized
      tomographic phase microscopy.
AB  - Refractive index imaging is a label-free technique that enables long-term
      monitoring of the internal structures and molecular composition in living cells
      with minimal perturbation. Existing tomographic methods for the refractive index
      imaging lack 3-D resolution and result in artifacts that prevent accurate
      refractive index quantification. To overcome these limitations without
      compromising the capability to observe a sample in its most native condition, we
      have developed a regularized tomographic phase microscope (RTPM) enabling
      accurate refractive index imaging of organelles inside intact cells. With the
      enhanced accuracy, we quantify the mass of chromosomes in intact living cells,
      and differentiate two human colon cancer lines, HT-29 and T84 cells, solely based
      on the non-aqueous (dry) mass of chromosomes. In addition, we demonstrate
      chromosomal imaging using a dual-wavelength RTPM, which shows its potential to
      determine the molecular composition of cellular organelles in live cells.

PMID- 23166690
TI  - Drosophila RecQ4 is directly involved in both DNA replication and the response to
      UV damage in S2 cells.
AB  - The RecQ4 protein shows homology to both the S.cerevisiae DNA replication protein
      Sld2 and the DNA repair related RecQ helicases. Experimental data also suggest
      replication and repair functions for RecQ4, but the precise details of its
      involvement remain to be clarified.Here we show that depletion of DmRecQ4 by
      dsRNA interference in S2 cells causes defects consistent with a replication
      function for the protein. The cells show reduced proliferation associated with an
      S phase block, reduced BrdU incorporation, and an increase in cells with a subG1
      DNA content. At the molecular level we observe reduced chromatin association of
      DNA polymerase-alpha and PCNA. We also observe increased chromatin association of
      phosphorylated H2AvD--consistent with the presence of DNA damage and increased
      apoptosis.Analysis of DmRecQ4 repair function suggests a direct role in NER, as
      the protein shows rapid but transient nuclear localisation after UV treatment. Re
      localisation is not observed after etoposide or H2O2 treatment, indicating that
      the involvement of DmRecQ4 in repair is likely to be pathway specific.Deletion
      analysis of DmRecQ4 suggests that the SLD2 domain was essential, but not
      sufficient, for replication function. In addition a DmRecQ4 N-terminal deletion
      could efficiently re-localise on UV treatment, suggesting that the determinants
      for this response are contained in the C terminus of the protein. Finally several
      deletions show differential rescue of dsRNA generated replication and
      proliferation phenotypes. These will be useful for a molecular analysis of the
      specific role of DmRecQ4 in different cellular pathways.

PMID- 23166691
TI  - Dealing with noisy absences to optimize species distribution models: an iterative
      ensemble modelling approach.
AB  - Species distribution models (SDMs) are widespread in ecology and conservation
      biology, but their accuracy can be lowered by non-environmental (noisy) absences
      that are common in species occurrence data. Here we propose an iterative ensemble
      modelling (IEM) method to deal with noisy absences and hence improve the
      predictive reliability of ensemble modelling of species distributions. In the IEM
      approach, outputs of a classical ensemble model (EM) were used to update the raw
      occurrence data. The revised data was then used as input for a new EM run. This
      process was iterated until the predictions stabilized. The outputs of the
      iterative method were compared to those of the classical EM using virtual
      species. The IEM process tended to converge rapidly. It increased the consensus
      between predictions provided by the different methods as well as between those
      provided by different learning data sets. Comparing IEM and EM showed that for
      high levels of non-environmental absences, iterations significantly increased
      prediction reliability measured by the Kappa and TSS indices, as well as the
      percentage of well-predicted sites. Compared to EM, IEM also reduced biases in
      estimates of species prevalence. Compared to the classical EM method, IEM
      improves the reliability of species predictions. It particularly deals with noisy
      absences that are replaced in the data matrices by simulated presences during the
      iterative modelling process. IEM thus constitutes a promising way to increase the
      accuracy of EM predictions of difficult-to-detect species, as well as of species
      that are not in equilibrium with their environment.

PMID- 23166692
TI  - Secretory vesicles are preferentially targeted to areas of low molecular SNARE
      density.
AB  - Intercellular communication is commonly mediated by the regulated fusion, or
      exocytosis, of vesicles with the cell surface. SNARE (soluble N-ethymaleimide
      sensitive factor attachment protein receptor) proteins are the catalytic core of
      the secretory machinery, driving vesicle and plasma membrane merger. Plasma
      membrane SNAREs (tSNAREs) are proposed to reside in dense clusters containing
      many molecules, thus providing a concentrated reservoir to promote membrane
      fusion. However, biophysical experiments suggest that a small number of SNAREs
      are sufficient to drive a single fusion event. Here we show, using molecular
      imaging, that the majority of tSNARE molecules are spatially separated from
      secretory vesicles. Furthermore, the motilities of the individual tSNAREs are
      constrained in membrane micro-domains, maintaining a non-random molecular
      distribution and limiting the maximum number of molecules encountered by
      secretory vesicles. Together our results provide a new model for the molecular
      mechanism of regulated exocytosis and demonstrate the exquisite organization of
      the plasma membrane at the level of individual molecular machines.

PMID- 23166693
TI  - Individual differences in detecting rapidly presented fearful faces.
AB  - Rapid detection of evolutionarily relevant threats (e.g., fearful faces) is
      important for human survival. The ability to rapidly detect fearful faces
      exhibits high variability across individuals. The present study aimed to
      investigate the relationship between behavioral detection ability and brain
      activity, using both event-related potential (ERP) and event-related oscillation
      (ERO) measurements. Faces with fearful or neutral facial expressions were
      presented for 17 ms or 200 ms in a backward masking paradigm. Forty-two
      participants were required to discriminate facial expressions of the masked
      faces. The behavioral sensitivity index d' showed that the detection ability to
      rapidly presented and masked fearful faces varied across participants. The ANOVA
      analyses showed that the facial expression, hemisphere, and presentation duration
      affected the grand-mean ERP (N1, P1, and N170) and ERO (below 20 Hz and lasted
      from 100 ms to 250 ms post-stimulus, mainly in theta band) brain activity. More
      importantly, the overall detection ability of 42 subjects was significantly
      correlated with the emotion effect (i.e., fearful vs. neutral) on ERP (r = 0.403)
      and ERO (r = 0.552) measurements. A higher d' value was corresponding to a larger
      size of the emotional effect (i.e., fearful--neutral) of N170 amplitude and a
      larger size of the emotional effect of the specific ERO spectral power at the
      right hemisphere. The present results suggested a close link between behavioral
      detection ability and the N170 amplitude as well as the ERO spectral power below
      20 Hz in individuals. The emotional effect size between fearful and neutral faces
      in brain activity may reflect the level of conscious awareness of fearful faces.

PMID- 23166694
TI  - Reduced cardiac vagal modulation impacts on cognitive performance in chronic
      fatigue syndrome.
AB  - BACKGROUND: Cognitive difficulties and autonomic dysfunction have been reported
      separately in patients with chronic fatigue syndrome (CFS). A role for heart rate
      variability (HRV) in cognitive flexibility has been demonstrated in healthy
      individuals, but this relationship has not as yet been examined in CFS. The
      objective of this study was to examine the relationship between HRV and cognitive
      performance in patients with CFS. METHODS: Participants were 30 patients with CFS
      and 40 healthy controls; the groups were matched for age, sex, education, body
      mass index, and hours of moderate exercise/week. Questionnaires were used to
      obtain relevant medical and demographic information, and assess current symptoms
      and functional impairment. Electrocardiograms, perceived fatigue/effort and
      performance data were recorded during cognitive tasks. Between-group differences
      in autonomic reactivity and associations with cognitive performance were
      analysed. RESULTS: Patients with CFS showed no deficits in performance accuracy,
      but were significantly slower than healthy controls. CFS was further
      characterized by low and unresponsive HRV; greater heart rate (HR) reactivity and
      prolonged HR-recovery after cognitive challenge. Fatigue levels, perceived effort
      and distress did not affect cognitive performance. HRV was consistently
      associated with performance indices and significantly predicted variance in
      cognitive outcomes. CONCLUSIONS: These findings reveal for the first time an
      association between reduced cardiac vagal tone and cognitive impairment in CFS
      and confirm previous reports of diminished vagal activity.

PMID- 23166695
TI  - Imaging mass spectrometry visualizes ceramides and the pathogenesis of dorfman
      chanarin syndrome due to ceramide metabolic abnormality in the skin.
AB  - Imaging mass spectrometry (IMS) is a useful cutting edge technology used to
      investigate the distribution of biomolecules such as drugs and metabolites, as
      well as to identify molecular species in tissues and cells without labeling. To
      protect against excess water loss that is essential for survival in a terrestrial
      environment, mammalian skin possesses a competent permeability barrier in the
      stratum corneum (SC), the outermost layer of the epidermis. The key lipids
      constituting this barrier in the SC are the ceramides (Cers) comprising of a
      heterogeneous molecular species. Alterations in Cer composition have been
      reported in several skin diseases that display abnormalities in the epidermal
      permeability barrier function. Not only the amounts of different Cers, but also
      their localizations are critical for the barrier function. We have employed our
      new imaging system, capable of high-lateral-resolution IMS with an atmospheric
      pressure ionization source, to directly visualize the distribution of Cers.
      Moreover, we show an ichthyotic disease pathogenesis due to abnormal Cer
      metabolism in Dorfman-Chanarin syndrome, a neutral lipid storage disorder with
      ichthyosis in human skin, demonstrating that IMS is a novel diagnostic approach
      for assessing lipid abnormalities in clinical setting, as well as for
      investigating physiological roles of lipids in cells/tissues.

PMID- 23166696
TI  - Macroevolutionary dynamics and historical biogeography of primate diversification
      inferred from a species supermatrix.
AB  - Phylogenetic relationships, divergence times, and patterns of biogeographic
      descent among primate species are both complex and contentious. Here, we generate
      a robust molecular phylogeny for 70 primate genera and 367 primate species based
      on a concatenation of 69 nuclear gene segments and ten mitochondrial gene
      sequences, most of which were extracted from GenBank. Relaxed clock analyses of
      divergence times with 14 fossil-calibrated nodes suggest that living Primates
      last shared a common ancestor 71-63 Ma, and that divergences within both
      Strepsirrhini and Haplorhini are entirely post-Cretaceous. These results are
      consistent with the hypothesis that the Cretaceous-Paleogene mass extinction of
      non-avian dinosaurs played an important role in the diversification of placental
      mammals. Previous queries into primate historical biogeography have suggested
      Africa, Asia, Europe, or North America as the ancestral area of crown primates,
      but were based on methods that were coopted from phylogeny reconstruction. By
      contrast, we analyzed our molecular phylogeny with two methods that were
      developed explicitly for ancestral area reconstruction, and find support for the
      hypothesis that the most recent common ancestor of living Primates resided in
      Asia. Analyses of primate macroevolutionary dynamics provide support for a
      diversification rate increase in the late Miocene, possibly in response to
      elevated global mean temperatures, and are consistent with the fossil record. By
      contrast, diversification analyses failed to detect evidence for rate-shift
      changes near the Eocene-Oligocene boundary even though the fossil record provides
      clear evidence for a major turnover event ("Grande Coupure") at this time. Our
      results highlight the power and limitations of inferring diversification dynamics
      from molecular phylogenies, as well as the sensitivity of diversification
      analyses to different species concepts.

PMID- 23166697
TI  - Identification of novel translational urinary biomarkers for acetaminophen
      induced acute liver injury using proteomic profiling in mice.
AB  - Drug-induced liver injury (DILI) is the leading cause of acute liver failure.
      Currently, no adequate predictive biomarkers for DILI are available. This study
      describes a translational approach using proteomic profiling for the
      identification of urinary proteins related to acute liver injury induced by
      acetaminophen (APAP). Mice were given a single intraperitoneal dose of APAP (0
      350 mg/kg bw) followed by 24 h urine collection. Doses of >=275 mg/kg bw APAP
      resulted in hepatic centrilobular necrosis and significantly elevated plasma
      alanine aminotransferase (ALT) values (p<0.0001). Proteomic profiling resulted in
      the identification of 12 differentially excreted proteins in urine of mice with
      acute liver injury (p<0.001), including superoxide dismutase 1 (SOD1), carbonic
      anhydrase 3 (CA3) and calmodulin (CaM), as novel biomarkers for APAP-induced
      liver injury. Urinary levels of SOD1 and CA3 increased with rising plasma ALT
      levels, but urinary CaM was already present in mice treated with high dose of
      APAP without elevated plasma ALT levels. Importantly, we showed in human urine
      after APAP intoxication the presence of SOD1 and CA3, whereas both proteins were
      absent in control urine samples. Urinary concentrations of CaM were significantly
      increased and correlated well with plasma APAP concentrations (r = 0.97;
      p<0.0001) in human APAP intoxicants, who did not present with elevated plasma ALT
      levels. In conclusion, using this urinary proteomics approach we demonstrate CA3,
      SOD1 and, most importantly, CaM as potential human biomarkers for APAP-induced
      liver injury.

PMID- 23166698
TI  - Structural insight into inhibitor of apoptosis proteins recognition by a potent
      divalent smac-mimetic.
AB  - Genetic alterations enhancing cell survival and suppressing apoptosis are
      hallmarks of cancer that significantly reduce the efficacy of chemotherapy or
      radiotherapy. The Inhibitor of Apoptosis Protein (IAP) family hosts conserved
      proteins in the apoptotic pathway whose over-expression, frequently found in
      tumours, potentiates survival and resistance to anticancer agents. In humans,
      IAPs comprise eight members hosting one or more structural Baculoviral IAP Repeat
      (BIR) domains. Cellular IAPs (cIAP1 and 2) indirectly inhibit caspase-8
      activation, and regulate both the canonical and the non-canonical NF-kappaB
      signaling pathways. In contrast to cIAPs, XIAP (X chromosome-linked Inhibitor of
      Apoptosis Protein) inhibits directly the effector caspases-3 and -7 through its
      BIR2 domain, and initiator caspase-9 through its BIR3 domain; molecular docking
      studies suggested that Smac/DIABLO antagonizes XIAP by simultaneously targeting
      both BIR2 and BIR3 domains. Here we report analytical gel filtration,
      crystallographic and SAXS experiments on cIAP1-BIR3, XIAP-BIR3 and XIAP-BIR2BIR3
      domains, alone and in the presence of compound 9a, a divalent homodimeric Smac
      mimetic. 9a is shown to bind two BIR domains inter- (in the case of two BIR3) and
      intra-molecularly (in the case of XIAP-BIR2BIR3), with higher affinity for cIAP1
      BIR3, relative to XIAP-BIR3. Despite the different crystal lattice packing, 9a
      maintains a right handed helical conformation in both cIAP1-BIR3 and XIAP-BIR3
      crystals, that is likely conserved in solution as shown by SAXS data. Our
      structural results demonstrate that the 9a linker length, its conformational
      degrees of freedom and its hydrophobicity, warrant an overall compact structure
      with optimal solvent exposure of its two active moieties for IAPs binding. Our
      results show that 9a is a good candidate for pre-clinical and clinical studies,
      worth of further investigations in the field of cancer therapy.

PMID- 23166699
TI  - Aristolochia manshuriensis Kom inhibits adipocyte differentiation by regulation
      of ERK1/2 and Akt pathway.
AB  - Aristolochia manshuriensis Kom (AMK) is a traditional medicinal herb used for the
      treatment of arthritis, rheumatism, hepatitis, and anti-obesity. Because of
      nephrotoxicity and carcinogenicity of AMK, there are no pharmacological reports
      on anti-obesity potential of AMK. Here, we showed AMK has an inhibitory effect on
      adipocyte differentiation of 3T3-L1 cells along with significantly decrease in
      the lipid accumulation by downregulating several adipocyte-specific transcription
      factors including peroxisome proliferation-activity receptor gamma (PPAR-gamma),
      CCAAT/enhancer binding protein alpha (C/EBP-alpha) and C/EBP-beta, which are
      critical for adipogenesis in vitro. AMK also markedly activated the extracellular
      signal-regulated protein kinase 1/2 (ERK1/2) pathway including Ras, Raf1, and
      mitogen-activated protein kinase kinase 1 (MEK1), and significantly suppressed
      Akt pathway by inhibition of phosphoinositide-dependent kinase 1 (PDK1).
      Aristolochic acid (AA) and ethyl acetate (EtOAc) fraction of AMK with AA were
      significantly inhibited TG accumulation, and regulated two pathway (ERK1/2 and
      Akt) during adipocyte differentiation, and was not due to its cytotoxicity. These
      two pathways were upstream of PPAR-gamma and C/EBPalpha in the adipogenesis. In
      addition, gene expressions of secreting factors such as fatty acid synthase
      (FAS), adiponectin, lipopreotein lipase (LPL), and aP2 were significantly
      inhibited by treatment of AMK during adipogenesis. We used the high-fat diet
      (HFD)-induced obesity mouse model to determine the inhibitory effects of AMK on
      obesity. Oral administration of AMK (62.5 mg/kg/day) significantly decreased the
      fat tissue weight, total cholesterol (TC), and low density lipoprotein
      cholesterol (LDL-C) concentration in the blood. The results of this study
      suggested that AMK inhibited lipid accumulation by the down-regulation of the
      major transcription factors of the adipogensis pathway including PPAR-gamma and
      C/EBP-alpha through regulation of Akt pathway and ERK 1/2 pathway in 3T3-L1
      adipocytes and HFD-induced obesity mice, and AA may be main act in inhibitory
      effects of AMK during adipocyte differentiation.

PMID- 23166700
TI  - A truncated AdeS kinase protein generated by ISAba1 insertion correlates with
      tigecycline resistance in Acinetobacter baumannii.
AB  - Over-expression of AdeABC efflux pump stimulated continuously by the mutated
      AdeRS two component system has been found to result in antimicrobial resistance,
      even tigecycline (TGC) resistance, in multidrug-resistant Acinetobacter baumannii
      (MRAB). Although the insertion sequence, ISAba1, contributes to one of the AdeRS
      mutations, the detail mechanism remains unclear. In the present study we
      collected 130 TGC-resistant isolates from 317 carbapenem resistant MRAB (MRAB-C)
      isolates, and 38 of them were characterized with ISAba1 insertion in the adeS
      gene. The relationship between the expression of AdeABC efflux pump and TGC
      resistant was verified indirectly by successfully reducing TGC resistance with
      NMP, an efflux pump inhibitor. Further analysis showed that the remaining gene
      following the ISAba1 insertion was still transcribed to generate a truncated AdeS
      protein by the Pout promoter on ISAba1 instead of frame shift or pre-termination.
      Through introducing a series of recombinant adeRS constructs into a adeRS
      knockout strain, we demonstrated the truncated AdeS protein was constitutively
      produced and stimulating the expression of AdeABC efflux pump via interaction
      with AdeR. Our findings suggest a mechanism of antimicrobial resistance induced
      by an aberrant cytoplasmic sensor derived from an insertion element.

PMID- 23166701
TI  - Using phage and yeast display to select hundreds of monoclonal antibodies:
      application to antigen 85, a tuberculosis biomarker.
AB  - BACKGROUND: Current diagnostic methods for tuberculosis (TB), a major global
      health challenge that kills nearly two million people annually, are time
      consuming and inadequate. During infection a number of bacterial molecules that
      play a role in the infective process are released and have been proposed as
      biomarkers for early TB diagnosis. Antigen 85 (Ag85) is the most abundant
      secreted TB protein, and a potential target for this diagnostic approach. One of
      the bottlenecks in the direct detection of such bacterial targets is the
      availability of robust, sensitive, specific antibodies. METHODS: Using Ag85 as a
      model, we describe a method to select antibodies against any potential target
      using a novel combination of phage and yeast display that exploits the advantage
      of each approach. RESULTS: The efficiency of this approach was attested to by the
      111 specific antibodies identified in initial screens. These were assessed for
      binding to the different Ag85 subunits, affinity, and activity in sandwich
      assays. CONCLUSIONS: The novelty of this approach lies in the possibility of
      screening the entire output of a phage antibody selection in a single experiment
      by yeast display. This can be considered analogous to carrying out a million
      ELISAs. The monoclonal antibodies (mAbs) identified in this way show high binding
      affinity and selectivity for the antigens and offer an advantage over traditional
      mAbs produced by relatively expensive and time consuming techniques. This
      approach has wide applicability, and the affinity of selected antibodies can be
      significantly improved, if required.

PMID- 23166702
TI  - A machine learning approach for identifying amino acid signatures in the HIV env
      gene predictive of dementia.
AB  - The identification of nucleotide sequence variations in viral pathogens linked to
      disease and clinical outcomes is important for developing vaccines and therapies.
      However, identifying these genetic variations in rapidly evolving pathogens
      adapting to selection pressures unique to each host presents several challenges.
      Machine learning tools provide new opportunities to address these challenges. In
      HIV infection, virus replicating within the brain causes HIV-associated dementia
      (HAD) and milder forms of neurocognitive impairment in 20-30% of patients with
      unsuppressed viremia. HIV neurotropism is primarily determined by the viral
      envelope (env) gene. To identify amino acid signatures in the HIV env gene
      predictive of HAD, we developed a machine learning pipeline using the PART rule
      learning algorithm and C4.5 decision tree inducer to train a classifier on a meta
      dataset (n = 860 env sequences from 78 patients: 40 HAD, 38 non-HAD). To increase
      the flexibility and biological relevance of our analysis, we included 4 numeric
      factors describing amino acid hydrophobicity, polarity, bulkiness, and charge, in
      addition to amino acid identities. The classifier had 75% predictive accuracy in
      leave-one-out cross-validation, and identified 5 signatures associated with HAD
      diagnosis (p<0.05, Fisher's exact test). These HAD signatures were found in the
      majority of brain sequences from 8 of 10 HAD patients from an independent cohort.
      Additionally, 2 HAD signatures were validated against env sequences from CSF of a
      second independent cohort. This analysis provides insight into viral genetic
      determinants associated with HAD, and develops novel methods for applying machine
      learning tools to analyze the genetics of rapidly evolving pathogens.

PMID- 23166703
TI  - Induction of protective anti-CTL epitope responses against HER-2-positive breast
      cancer based on multivalent T7 phage nanoparticles.
AB  - We report here the development of multivalent T7 bacteriophage nanoparticles
      displaying an immunodominant H-2k(d)-restricted CTL epitope derived from the rat
      HER2/neu oncoprotein. The immunotherapeutic potential of the chimeric T7
      nanoparticles as anti-cancer vaccine was investigated in BALB/c mice in an
      implantable breast tumor model. The results showed that T7 phage nanoparticles
      confer a high immunogenicity to the HER-2-derived minimal CTL epitope, as shown
      by inducing robust CTL responses. Furthermore, the chimeric nanoparticles
      protected mice against HER-2-positive tumor challenge in both prophylactic and
      therapeutic setting. In conclusion, these results suggest that CTL epitope
      carrying T7 phage nanoparticles might be a promising approach for development of
      T cell epitope-based cancer vaccines.

PMID- 23166704
TI  - Temporal expression and localization patterns of variant surface antigens in
      clinical Plasmodium falciparum isolates during erythrocyte schizogony.
AB  - Avoidance of antibody-mediated immune recognition allows parasites to establish
      chronic infections and enhances opportunities for transmission. The human malaria
      parasite Plasmodium falciparum possesses a number of multi-copy gene families,
      including var, rif, stevor and pfmc-2tm, which encode variant antigens believed
      to be expressed on the surfaces of infected erythrocytes. However, most studies
      of these antigens are based on in vitro analyses of culture-adapted isolates,
      most commonly the laboratory strain 3D7, and thus may not be representative of
      the unique challenges encountered by P. falciparum in the human host. To
      investigate the expression of the var, rif-A, rif-B, stevor and pfmc-2tm family
      genes under conditions that mimic more closely the natural course of infection,
      ex vivo clinical P. falciparum isolates were analyzed using a novel quantitative
      real-time PCR approach. Expression patterns in the clinical isolates at various
      time points during the first intraerythrocytic developmental cycle in vitro were
      compared to those of strain 3D7. In the clinical isolates, in contrast to strain
      3D7, there was a peak of expression of the multi-copy gene families rif-A, stevor
      and pfmc-2tm at the young ring stage, in addition to the already known expression
      peak in trophozoites. Furthermore, most of the variant surface antigen families
      were overexpressed in the clinical isolates relative to 3D7, with the exception
      of the pfmc-2tm family, expression of which was higher in 3D7 parasites.
      Immunofluorescence analyses performed in parallel revealed two stage-dependent
      localization patterns of RIFIN, STEVOR and PfMC-2TM. Proteins were exported into
      the infected erythrocyte at the young trophozoite stage, whereas they remained
      inside the parasite membrane during schizont stage and were subsequently observed
      in different compartments in the merozoite. These results reveal a complex
      pattern of expression of P. falciparum multi-copy gene families during clinical
      progression and are suggestive of diverse functional roles of the respective
      proteins.

PMID- 23166705
TI  - Clinical utility of the cryptococcal antigen lateral flow assay in a diagnostic
      mycology laboratory.
AB  - BACKGROUND: Cryptococcus neoformans causes life-threatening meningitis. A
      recently introduced lateral flow immunoassay (LFA) to detect cryptococcal antigen
      (CRAG) is reportedly more rapid and convenient than standard latex agglutination
      (LA), but has not yet been evaluated in a diagnostic laboratory setting. METHODS:
      One hundred and six serum, 42 cerebrospinal fluid (CSF), and 20 urine samples
      from 92 patients with known or suspected cryptococcosis were tested by LA and
      LFA, and titres were compared. Results were correlated with laboratory-confirmed
      cryptococcosis. Serial samples were tested in nine treated patients. RESULTS:
      Twenty-five of 92 patients had confirmed cryptococcosis; all sera (n = 56) from
      these patients were positive by LFA (sensitivity 100%, 95% confidence interval
      (CI) 93.6-100%) compared with 51/56 positive by LA (sensitivity 91.1%, 95% CI
      80.7-96.1%). Fifty sera from 67 patients without cryptococcosis tested negative
      in both assays. While LA yielded more false negative results (5/56) this did not
      reach statistical significance (p = 0.063). Nine CSF samples from patients with
      cryptococcal meningitis yielded positive results using both assays while 17/18
      urine samples from patients with cryptococcosis were positive by the LFA. The LFA
      detected CRAG in C. gattii infection (n = 4 patients). Agreement between titres
      obtained by both methods (n = 38 samples) was imperfect; correlation between log
      transformed titres (r) was 0.84. Turn-around-time was 20 minutes for the LFA and
      2 h for LA. The cost per qualitative sample was 18USD and 91 USD, respectively
      and per quantitative sample was 38USD and 144USD, respectively. CONCLUSIONS:
      Qualitative agreement between the LFA and LA assays performed on serum and CSF
      was good but agreement between titres was imperfect. Ease of performance of the
      LFA and the capacity for testing urine suggest it has a role in the routine
      laboratory as a rapid diagnostic test or point-of-care test.

PMID- 23166706
TI  - Origin of Oryza sativa in China inferred by nucleotide polymorphisms of organelle
      DNA.
AB  - China is rich of germplasm resources of common wild rice (Oryza rufipogon Griff.)
      and Asian cultivated rice (O. sativa L.) which consists of two subspecies, indica
      and japonica. Previous studies have shown that China is one of the domestication
      centers of O. sativa. However, the geographic origin and the domestication times
      of O. sativa in China are still under debate. To settle these disputes, six
      chloroplast loci and four mitochondrial loci were selected to examine the
      relationships between 50 accessions of Asian cultivated rice and 119 accessions
      of common wild rice from China based on DNA sequence analysis in the present
      study. The results indicated that Southern China is the genetic diversity center
      of O. rufipogon and it might be the primary domestication region of O. sativa.
      Molecular dating suggested that the two subspecies had diverged 0.1 million years
      ago, much earlier than the beginning of rice domestication. Genetic
      differentiations and phylogeography analyses indicated that indica was
      domesticated from tropical O. rufipogon while japonica was domesticated from O.
      rufipogon which located in higher latitude. These results provided molecular
      evidences for the hypotheses of (i) Southern China is the origin center of O.
      sativa in China and (ii) the two subspecies of O. sativa were domesticated
      multiple times.

PMID- 23166707
TI  - A low dose of fermented soy germ alleviates gut barrier injury, hyperalgesia and
      faecal protease activity in a rat model of inflammatory bowel disease.
AB  - Pro-inflammatory cytokines like macrophage migration inhibitory factor (MIF), IL
      1beta and TNF-alpha predominate in inflammatory bowel diseases (IBD) and TNBS
      colitis. Increased levels of serine proteases activating protease-activated
      receptor 2 (PAR-2) are found in the lumen and colonic tissue of IBD patients. PAR
      2 activity and pro-inflammatory cytokines impair epithelial barrier, facilitating
      the uptake of luminal aggressors that perpetuate inflammation and visceral pain.
      Soy extracts contain phytoestrogens (isoflavones) and serine protease inhibitors
      namely Bowman-Birk Inhibitors (BBI). Since estrogens exhibit anti-inflammatory
      and epithelial barrier enhancing properties, and that a BBI concentrate improves
      ulcerative colitis, we aimed to evaluate if a fermented soy germ extract (FSG)
      with standardized isoflavone profile and stable BBI content exert cumulative or
      synergistic protection based on protease inhibition and estrogen receptor (ER)
      ligand activity in colitic rats. Female rats received orally for 15 d either
      vehicle or FSG with or without an ER antagonist ICI 182.780 before TNBS
      intracolonic instillation. Macroscopic and microscopic damages, myeloperoxidase
      activity, cytokine levels, intestinal paracellular permeability, visceral
      sensitivity, faecal proteolytic activity and PAR-2 expression were assessed 24 h,
      3 d and 5 d post-TNBS. FSG treatment improved the severity of colitis, by
      decreasing the TNBS-induced rise in gut permeability, visceral sensitivity,
      faecal proteolytic activity and PAR-2 expression at all post-TNBS points. All FSG
      effects were reversed by the ICI 182.780 except the decrease in faecal
      proteolytic activity and PAR-2 expression. In conclusion, the anti-inflammatory
      properties of FSG treatment result from two distinct but synergic pathways i.e an
      ER-ligand and a PAR-2 mediated pathway, providing rationale for potential use as
      adjuvant therapy in IBD.

PMID- 23166708
TI  - Serodiagnosis of tuberculosis in Asian elephants (Elephas maximus) in Southern
      India: a latent class analysis.
AB  - BACKGROUND: Mycobacterium tuberculosis, a causative agent of chronic tuberculosis
      disease, is widespread among some animal species too. There is paucity of
      information on the distribution, prevalence and true disease status of
      tuberculosis in Asian elephants (Elephas maximus). The aim of this study was to
      estimate the sensitivity and specificity of serological tests to diagnose M.
      tuberculosis infection in captive elephants in southern India while
      simultaneously estimating sero-prevalence. METHODOLOGY/PRINCIPAL FINDINGS: Health
      assessment of 600 elephants was carried out and their sera screened with a
      commercially available rapid serum test. Trunk wash culture of select rapid serum
      test positive animals yielded no animal positive for M. tuberculosis isolation.
      Under Indian field conditions where the true disease status is unknown, we used a
      latent class model to estimate the diagnostic characteristics of an existing
      (rapid serum test) and new (four in-house ELISA) tests. One hundred and seventy
      nine sera were randomly selected for screening in the five tests. Diagnostic
      sensitivities of the four ELISAs were 91.3-97.6% (95% Credible Interval (CI):
      74.8-99.9) and diagnostic specificity were 89.6-98.5% (95% CI: 79.4-99.9) based
      on the model we assumed. We estimate that 53.6% (95% CI: 44.6-62.8) of the
      samples tested were free from infection with M. tuberculosis and 15.9% (97.5% CI:
      9.8 - to 24.0) tested positive on all five tests. CONCLUSIONS/SIGNIFICANCE: Our
      results provide evidence for high prevalence of asymptomatic M. tuberculosis
      infection in Asian elephants in a captive Indian setting. Further validation of
      these tests would be important in formulating area-specific effective
      surveillance and control measures.

PMID- 23166709
TI  - The mitochondrial LSU rRNA group II intron of Ustilago maydis encodes an active
      homing endonuclease likely involved in intron mobility.
AB  - BACKGROUND: The a2 mating type locus gene lga2 is critical for uniparental
      mitochondrial DNA inheritance during sexual development of Ustilago maydis.
      Specifically, the absence of lga2 results in biparental inheritance, along with
      efficient transfer of intronic regions in the large subunit rRNA gene between
      parental molecules. However, the underlying role of the predicted LAGLIDADG
      homing endonuclease gene I-UmaI located within the group II intron LRII1 has
      remained unresolved. METHODOLOGY/PRINCIPAL FINDINGS: We have investigated the
      enzymatic activity of I-UmaI in vitro based on expression of a tagged full-length
      and a naturally occurring mutant derivative, which harbors only the N-terminal
      LAGLIDADG domain. This confirmed Mg2+-dependent endonuclease activity and
      cleavage at the LRII1 insertion site to generate four base pair extensions with
      3' overhangs. Specifically, I-UmaI recognizes an asymmetric DNA sequence with a
      minimum length of 14 base pairs (5'-GACGGGAAGACCCT-3') and tolerates subtle base
      pair substitutions within the homing site. Enzymatic analysis of the mutant
      variant indicated a correlation between the activity in vitro and intron homing.
      Bioinformatic analyses revealed that putatively functional or former functional I
      UmaI homologs are confined to a few members within the Ustilaginales and
      Agaricales, including the phylogenetically distant species Lentinula edodes, and
      are linked to group II introns inserted into homologous positions in the LSU
      rDNA. CONCLUSIONS/SIGNIFICANCE: The present data provide strong evidence that
      intron homing efficiently operates under conditions of biparental inheritance in
      U. maydis. Conversely, uniparental inheritance may be critical to restrict the
      transmission of mobile introns. Bioinformatic analyses suggest that I-UmaI
      associated introns have been acquired independently in distant taxa and are more
      widespread than anticipated from available genomic data.

PMID- 23166710
TI  - Concomitant release of ventral tegmental acetylcholine and accumbal dopamine by
      ghrelin in rats.
AB  - Ghrelin, an orexigenic peptide, regulates energy balance specifically via
      hypothalamic circuits. Growing evidence suggest that ghrelin increases the
      incentive value of motivated behaviours via activation of the cholinergic
      dopaminergic reward link. It encompasses the cholinergic afferent projection from
      the laterodorsal tegmental area (LDTg) to the dopaminergic cells of the ventral
      tegmental area (VTA) and the mesolimbic dopamine system projecting from the VTA
      to nucleus accumbens (N.Acc.). Ghrelin receptors (GHS-R1A) are expressed in these
      reward nodes and ghrelin administration into the LDTg increases accumbal
      dopamine, an effect involving nicotinic acetylcholine receptors in the VTA. The
      present series of experiments were undertaken directly to test this hypothesis.
      Here we show that ghrelin, administered peripherally or locally into the LDTg
      concomitantly increases ventral tegmental acetylcholine as well as accumbal
      dopamine release. A GHS-R1A antagonist blocks this synchronous neurotransmitter
      release induced by peripheral ghrelin. In addition, local perfusion of the
      unselective nicotinic antagonist mecamylamine into the VTA blocks the ability of
      ghrelin (administered into the LDTg) to increase N.Acc.-dopamine, but not VTA
      acetylcholine. Collectively our data indicate that ghrelin activates the LDTg
      causing a release of acetylcholine in the VTA, which in turn activates local
      nicotinic acetylcholine receptors causing a release of accumbal dopamine. Given
      that a dysfunction in the cholinergic-dopaminergic reward system is involved in
      addictive behaviours, including compulsive overeating and alcohol use disorder,
      and that hyperghrelinemia is associated with such addictive behaviours, ghrelin
      responsive circuits may serve as a novel pharmacological target for treatment of
      alcohol use disorder as well as binge eating.

PMID- 23166711
TI  - Modulation of antimicrobial host defense peptide gene expression by free fatty
      acids.
AB  - Routine use of antibiotics at subtherapeutic levels in animal feed drives the
      emergence of antimicrobial resistance. Development of antibiotic-alternative
      approaches to disease control and prevention for food animals is imperatively
      needed. Previously, we showed that butyrate, a major species of short-chain fatty
      acids (SCFAs) fermented from undigested fiber by intestinal microflora, is a
      potent inducer of endogenous antimicrobial host defense peptide (HDP) genes in
      the chicken (PLoS One 2011, 6: e27225). In the present study, we further revealed
      that, in chicken HD11 macrophages and primary monocytes, induction of HDPs is
      largely in an inverse correlation with the aliphatic hydrocarbon chain length of
      free fatty acids, with SCFAs being the most potent, medium-chain fatty acids
      moderate and long-chain fatty acids marginal. Additionally, three SCFAs, namely
      acetate, propionate, and butyrate, exerted a strong synergy in augmenting HDP
      gene expression in chicken cells. Consistently, supplementation of chickens with
      a combination of three SCFAs in water resulted in a further reduction of
      Salmonella enteritidis in the cecum as compared to feeding of individual SCFAs.
      More importantly, free fatty acids enhanced HDP gene expression without
      triggering proinflammatory interleukin-1beta production. Taken together, oral
      supplementation of SCFAs is capable of boosting host immunity and disease
      resistance, with potential for infectious disease control and prevention in
      animal agriculture without relying on antibiotics.

PMID- 23166712
TI  - Identification of genetic suppressors of the Sin3A knockdown wing phenotype.
AB  - The role of the Sin3A transcriptional corepressor in regulating the cell cycle is
      established in various metazoans. Little is known, however, about the signaling
      pathways that trigger or are triggered by Sin3A function. To discover genes that
      work in similar or opposing pathways to Sin3A during development, we have
      performed an unbiased screen of deficiencies of the Drosophila third chromosome.
      Additionally, we have performed a targeted loss of function screen to identify
      cell cycle genes that genetically interact with Sin3A. We have identified genes
      that encode proteins involved in regulation of gene expression, signaling
      pathways and cell cycle that can suppress the curved wing phenotype caused by the
      knockdown of Sin3A. These data indicate that Sin3A function is quite diverse and
      impacts a wide variety of cellular processes.

PMID- 23166713
TI  - The expression levels of microRNA-361-5p and its target VEGFA are inversely
      correlated in human cutaneous squamous cell carcinoma.
AB  - Vascular endothelial growth factor A (VEGFA) plays a key role in the angiogenesis
      of human skin. Elevated levels of VEGFA are associated with several pathological
      conditions, including chronic inflammatory skin diseases and several types of
      skin cancer. In particular, squamous cell carcinoma (SCC) of the skin, the second
      most common skin cancer in the general population, is characterized by invasive
      growth, pronounced angiogenesis and elevated levels of VEGFA. The processing,
      turnover and production of VEGFA are extensively regulated at the post
      transcriptional level, both by RNA-binding proteins and microRNAs (miRNAs). In
      the present study, we identified a new miRNA recognition element in a downstream
      conserved region of the VEGFA 3'-UTR. We confirmed the repressive effect of miR
      361-5p on this element in vitro, identifying the first target for this miRNA.
      Importantly, we found that miR-361-5p levels are inversely correlated with VEGFA
      expression in SCC and in healthy skin, indicating that miR-361-5p could play a
      role in cancers.

PMID- 23166715
TI  - A native-like corneal construct using donor corneal stroma for tissue
      engineering.
AB  - Tissue engineering holds great promise for corneal transplantation to treat
      blinding diseases. This study was to explore the use of natural corneal stroma as
      an optimal substrate to construct a native like corneal equivalent. Human corneal
      epithelium was cultivated from donor limbal explants on corneal stromal discs
      prepared by FDA approved Horizon Epikeratome system. The morphology, phenotype,
      regenerative capacity and transplantation potential were evaluated by hematoxylin
      eosin and immunofluorescent staining, a wound healing model, and the xeno
      transplantation of the corneal constructs to nude mice. An optically transparent
      and stratified epithelium was rapidly generated on donor corneal stromal
      substrate and displayed native-like morphology and structure. The cells were
      polygonal in the basal layer and became flattened in superficial layers. The
      epithelium displayed a phenotype similar to human corneal epithelium in vivo. The
      differentiation markers, keratin 3, involucrin and connexin 43, were expressed in
      full or superficial layers. Interestingly, certain basal cells were
      immunopositive to antibodies against limbal stem/progenitor cell markers ABCG2
      and p63, which are usually negative in corneal epithelium in vivo. It suggests
      that this bioengineered corneal epithelium shared some characteristics of human
      limbal epithelium in vivo. This engineered epithelium was able to regenerate in 4
      days following from a 4mm-diameter wound created by a filter paper soaked with 1
      N NaOH. This corneal construct survived well after xeno-transplantation to the
      back of a nude mouse. The transplanted epithelium remained multilayer and became
      thicker with a phenotype similar to human corneal epithelium. Our findings
      demonstrate that natural corneal stroma is an optimal substrate for tissue
      bioengineering, and a native-like corneal construct has been created with
      epithelium containing limbal stem cells. This construct may have great potential
      for clinical use in corneal reconstruction.

PMID- 23166714
TI  - Transcriptome analysis of renal ischemia/reperfusion injury and its modulation by
      ischemic pre-conditioning or hemin treatment.
AB  - Ischemia/reperfusion injury (IRI) is a leading cause of acute renal failure. The
      definition of the molecular mechanisms involved in renal IRI and counter
      protection promoted by ischemic pre-conditioning (IPC) or Hemin treatment is an
      important milestone that needs to be accomplished in this research area. We
      examined, through an oligonucleotide microarray protocol, the renal differential
      transcriptome profiles of mice submitted to IRI, IPC and Hemin treatment. After
      identifying the profiles of differentially expressed genes observed for each
      comparison, we carried out functional enrichment analysis to reveal transcripts
      putatively involved in potential relevant biological processes and signaling
      pathways. The most relevant processes found in these comparisons were stress,
      apoptosis, cell differentiation, angiogenesis, focal adhesion, ECM-receptor
      interaction, ion transport, angiogenesis, mitosis and cell cycle, inflammatory
      response, olfactory transduction and regulation of actin cytoskeleton. In
      addition, the most important overrepresented pathways were MAPK, ErbB, JAK/STAT,
      Toll and Nod like receptors, Angiotensin II, Arachidonic acid metabolism, Wnt and
      coagulation cascade. Also, new insights were gained about the underlying
      protection mechanisms against renal IRI promoted by IPC and Hemin treatment. Venn
      diagram analysis allowed us to uncover common and exclusively differentially
      expressed genes between these two protective maneuvers, underscoring potential
      common and exclusive biological functions regulated in each case. In summary, IPC
      exclusively regulated the expression of genes belonging to stress, protein
      modification and apoptosis, highlighting the role of IPC in controlling
      exacerbated stress response. Treatment with the Hmox1 inducer Hemin, in turn,
      exclusively regulated the expression of genes associated with cell
      differentiation, metabolic pathways, cell cycle, mitosis, development, regulation
      of actin cytoskeleton and arachidonic acid metabolism, suggesting a pleiotropic
      effect for Hemin. These findings improve the biological understanding of how the
      kidney behaves after IRI. They also illustrate some possible underlying molecular
      mechanisms involved in kidney protection observed with IPC or Hemin treatment
      maneuvers.

PMID- 23166716
TI  - The HER2-binding affibody molecule (Z(HER2?342))2 increases radiosensitivity in
      SKBR-3 cells.
AB  - We have previously shown that the HER2-specific affibody molecule (Z(HER2?342))2
      inhibits proliferation of SKBR-3 cells. Here, we continue to investigate its
      biological effects in vitro by studying receptor dimerization and clonogenic
      survival following irradiation. We found that (Z(HER2?342))2 sensitizes the HER2
      overexpressing cell line SKBR-3 to ionizing radiation. The survival after
      exposure to (Z(HER2?342))2 and 8 Gy (S(8Gy) 0.006) was decreased by a factor four
      compared to the untreated (S(8Gy) 0.023). The low HER2-expressing cell line MCF-7
      was more radiosensitive than SKBR-3 but did not respond to (Z(HER2?342))2.
      Treatment by (Z(HER2?342))2 strongly increased the levels of dimerized and
      phosphorylated HER2 even after 5 minutes of stimulation. The monomeric
      Z(HER2?342) does not seem to be able to induce receptor phosphorylation and
      dimerization or sensitize cells to irradiation.

PMID- 23166717
TI  - Do low-mercury terrestrial resources subsidize low-mercury growth of stream fish?
      Differences between species along a productivity gradient.
AB  - Low productivity in aquatic ecosystems is associated with reduced individual
      growth of fish and increased concentrations of methylmercury (MeHg) in fish and
      their prey. However, many stream-dwelling fish species can use terrestrially
      derived food resources, potentially subsidizing growth at low-productivity sites,
      and, because terrestrial resources have lower MeHg concentrations than aquatic
      resources, preventing an increase in diet-borne MeHg accumulation. We used a
      large-scale field study to evaluate relationships among terrestrial subsidy use,
      growth, and MeHg concentrations in two stream-dwelling fish species across an in
      stream productivity gradient. We sampled young-of-the-year brook trout
      (Salvelinus fontinalis) and Atlantic salmon (Salmo salar), potential competitors
      with similar foraging habits, from 20 study sites in streams in New Hampshire and
      Massachusetts that encompassed a wide range of aquatic prey biomass. Stable
      isotope analysis showed that brook trout used more terrestrial resources than
      Atlantic salmon. Over their first growing season, Atlantic salmon tended to grow
      larger than brook trout at sites with high aquatic prey biomass, but brook grew
      two-fold larger than Atlantic salmon at sites with low aquatic prey biomass. The
      MeHg concentrations of brook trout and Atlantic salmon were similar at sites with
      high aquatic prey biomass and the MeHg concentrations of both species increased
      at sites with low prey biomass and high MeHg in aquatic prey. However, brook
      trout had three-fold lower MeHg concentrations than Atlantic salmon at low
      productivity, high-MeHg sites. These results suggest that differential use of
      terrestrial resource subsidies reversed the growth asymmetry between potential
      competitors across a productivity gradient and, for one species, moderated the
      effect of low in-stream productivity on MeHg accumulation.

PMID- 23166718
TI  - Promoting physical activity and reducing sedentary behavior in disadvantaged
      neighborhoods: a qualitative study of what women want.
AB  - Since women living in socioeconomically disadvantaged neighborhoods are more
      likely to be physically inactive and engage in higher levels of sedentary
      behavior than women living in more advantaged neighborhoods, it is important to
      develop and test the feasibility of strategies aimed to promote physical activity
      and reduce sedentary behavior amongst this high-risk target group. Thirty-seven
      women (aged 19-85) living in a disadvantaged neighborhood, and five key
      stakeholders, received a suite of potential intervention materials and completed
      a qualitative questionnaire assessing the perceived feasibility of strategies
      aimed to increase physical activity and reduce sedentary behavior. Thematic
      analyses were performed. Women perceived the use of a locally-relevant
      information booklet as a feasible strategy to increase physical activity and
      reduce sedentary behavior. Including weight-loss information was suggested to
      motivate women to be active. Half the women felt the best delivery method was
      mailed leaflets. Other suggestions included reference books and websites. Many
      women mentioned that an online activity calendar was motivational but too time
      consuming to commit to. Most women preferred the information booklet as a
      strategy to increase physical activity/reduce sedentary behavior, yet several
      suggested that using the booklet together with the online calendar may be more
      effective. These findings make an important contribution to research informing
      the development of intervention strategies to increase physical activity and
      reduce sedentary behavior amongst women living in disadvantaged neighborhoods.

PMID- 23166719
TI  - Microbiological culture simplified using anti-O12 monoclonal antibody in TUBEX
      test to detect Salmonella bacteria from blood culture broths of enteric fever
      patients.
AB  - Definitive diagnosis of infectious diseases, including food poisoning, requires
      culture and identification of the infectious agent. We described how antibodies
      could be used to shorten this cumbersome process. Specifically, we employed an
      anti-Salmonella lipopolysaccharide O12 monoclonal antibody in an epitope
      inhibition 10-min test (TUBEX TP) to detect O12+Salmonella organisms directly
      from routine blood culture broths. The aim is to obviate the need to subculture
      the broth and subsequently identify the colonies. Thus, blood from 78 young
      outpatients suspected of having enteric fever was incubated in an enrichment
      broth, and after 2 or 4 days, broth samplings were examined by TUBEX TP as well
      as by conventional agar culture and identification. TUBEX TP was performed before
      the culture results. Eighteen isolates of S. Typhi (15 after 2 days) and 10
      isolates of S. Paratyphi A (4 after 2 days) were obtained by conventional
      culture. Both these Salmonella serotypes, the main causes of enteric fever, share
      the O12 antigen. In all instances where either of these organisms was present
      (cultured), TUBEX TP was positive (score 4 [light blue]--to--score 10 [dark
      blue]; negative is 0 [pink-colored]) i.e. 100% sensitive. Identification of the
      specific Salmonella serotype in TUBEX-positive cases was achieved subsequently by
      conventional slide agglutination using appropriate polyclonal antisera against
      the various serotypes. Twelve Escherichia coli, 1 Alcaligenes spp. and 1
      Enterobacter spp. were isolated. All of these cases, including all the 36 culture
      negative broths, were TUBEX-negative i.e. TUBEX TP was 100% specific. In a
      separate study using known laboratory strains, TUBEX TF, which detects S. Typhi
      but not S. Paratyphi A via the O9 antigen, was found to efficiently complement
      TUBEX TP as a differential test. Thus, TUBEX TP and TUBEX TF are useful adjuncts
      to conventional culture because they can save considerable time (>2 days), costs
      and manpower.

PMID- 23166720
TI  - Saccadic compression of symbolic numerical magnitude.
AB  - Stimuli flashed briefly around the time of saccadic eye movements are subject to
      complex distortions: compression of space and time; underestimate of numerosity.
      Here we show that saccadic distortions extend to abstract quantities, affecting
      the representation of symbolic numerical magnitude. Subjects consistently
      underestimated the results of rapidly computed mental additions and subtractions,
      when the operands were briefly displayed before a saccade. However, the
      recognition of the number symbols was unimpaired. These results are consistent
      with the hypothesis of a common, abstract metric encoding magnitude along
      multiple dimensions. They suggest that a surprising link exists between the
      preparation of action and the representation of abstract quantities.

PMID- 23166721
TI  - An altered immune response, but not individual cationic antimicrobial peptides,
      is associated with the oral attenuation of Ara4N-deficient Salmonella enterica
      serovar Typhimurium in mice.
AB  - Salmonella enterica serovar Typhimurium (S. Typhimurium) uses two-component
      regulatory systems (TCRS) to respond to stimuli in the local microenvironment.
      Upon infection, the Salmonella TCRSs PhoP-PhoQ (PhoPQ) and PmrA-PmrB (PmrAB) are
      activated by environmental signals in the intestinal lumen and within host cells.
      TCRS-mediated gene expression results in lipopolysaccharide (LPS) modification
      and cationic antimicrobial peptide resistance. The PmrA-regulated pmrHFIJKLM
      operon mediates 4-amino-4-deoxy-L-arabinose (Ara4N) production and attachment to
      the lipid A of LPS. A DeltapmrF S. Typhimurium strain cannot produce Ara4N,
      exhibits increased sensitivity to cationic antimicrobial peptide (CAMP)-mediated
      killing, and attenuated virulence in mice upon oral infection. CAMPs are
      predicted to play a role in elimination of Salmonella, and may activate PhoPQ and
      PmrAB in vivo, which could increase bacterial resistance to host defenses.
      Competition experiments between wild type (WT) and DeltapmrF mutant strains of S.
      Typhimurium indicated that selection against this mutant first occurs within the
      intestinal lumen early during infection. However, CRAMP and active cryptdins
      alone are not responsible for elimination of Ara4N-deficient bacteria in vivo.
      Investigation into the early immune response to DeltapmrF showed that it differed
      slightly from the early immune response to WT S. Typhimurium. Further
      investigation into the early immune response to infection of Peyer's patches
      suggests a role for IL-13 in the attenution of the DeltapmrF mutant strain. Thus,
      prominent CAMPs present in the mouse intestine are not responsible for the
      selection against the DeltapmrF strain in this location, but limited alterations
      in innate immune induction were observed that affect bacterial survival and
      virulence.

PMID- 23166722
TI  - The ability to enhance the solubility of its fusion partners is an intrinsic
      property of maltose-binding protein but their folding is either spontaneous or
      chaperone-mediated.
AB  - Escherichia coli maltose binding protein (MBP) is commonly used to promote the
      solubility of its fusion partners. To investigate the mechanism of solubility
      enhancement by MBP, we compared the properties of MBP fusion proteins refolded in
      vitro with those of the corresponding fusion proteins purified under native
      conditions. We fused five aggregation-prone passenger proteins to 3 different N
      terminal tags: His6-MBP, His6-GST and His6. After purifying the 15 fusion
      proteins under denaturing conditions and refolding them by rapid dilution, we
      recovered far more of the soluble MBP fusion proteins than their GST- or His
      tagged counterparts. Hence, we can reproduce the solubilizing activity of MBP in
      a simple in vitro system, indicating that no additional factors are required to
      mediate this effect. We assayed both the soluble fusion proteins and their TEV
      protease digestion products (i.e., with the N-terminal tag removed) for
      biological activity. Little or no activity was detected for some fusion proteins
      whereas others were quite active. When the MBP fusions proteins were purified
      from E. coli under native conditions they were all substantially active. These
      results indicate that the ability of MBP to promote the solubility of its fusion
      partners in vitro sometimes, but not always, results in their proper folding. We
      show that the folding of some passenger proteins is mediated by endogenous
      chaperones in vivo. Hence, MBP serves as a passive participant in the folding
      process; passenger proteins either fold spontaneously or with the assistance of
      chaperones.

PMID- 23166723
TI  - Variation in female grey seal (Halichoerus grypus) reproductive performance
      correlates to proactive-reactive behavioural types.
AB  - Consistent individual differences (CIDs) in behaviour, indicative of behavioural
      types or personalities, have been shown in taxa ranging from Cnidaria to
      Mammalia. However, despite numerous theoretical explanations there remains
      limited empirical evidence for selective mechanisms that maintain such variation
      within natural populations. We examined behavioural types and fitness proxies in
      wild female grey seals at the North Rona breeding colony. Experiments in 2009 and
      2010 employed a remotely-controlled vehicle to deliver a novel auditory stimulus
      to females to elicit changes in pup-checking behaviour. Mothers tested twice
      during lactation exhibited highly repeatable individual pup-checking rates within
      and across breeding seasons. Observations of undisturbed mothers (i.e.
      experiencing no disturbance from conspecifics or experimental test) also revealed
      CIDs in pup-checking behaviour. However, there was no correlation between an
      individuals' pup-checking rate during undisturbed observations with the rate in
      response to the auditory test, indicating plasticity across situations. The
      extent to which individuals changed rates of pup-checking from undisturbed to
      disturbed conditions revealed a continuum of behavioural types from proactive
      females, who maintained a similar rate throughout, to reactive females, who
      increased pup-checking markedly in response to the test. Variation in maternal
      expenditure (daily mass loss rate) was greater among more reactive mothers than
      proactive mothers. Consequently pups of more reactive mothers had more varied
      growth rates centred around the long-term population mean. These patterns could
      not be accounted for by other measured covariates as behavioural type was
      unrelated to a mother's prior experience, degree of inter-annual site fidelity,
      physical characteristics of their pupping habitat, pup sex or pup activity. These
      findings are consistent with the hypothesis that variation in behavioural types
      is maintained by spatial and temporal environmental variation combined with
      limits to phenotype-environment matching.

PMID- 23166724
TI  - Trial registration numbers are underreported in biomedical publications.
AB  - CONTEXT: Since September 2005, the International Committee of Medical Journal
      Editors (ICMJE) has required that randomised controlled trials (RCTs) are
      prospectively registered in a publicly accessible database. After registration, a
      trial registration number (TRN) is assigned to each RCT, which should make it
      easier to identify future publications and cross-check published results with
      associated registry entries, as long as the unique identification number is
      reported in the article. OBJECTIVE: Our primary objective was to evaluate the
      reporting of trial registration numbers in biomedical publications. Secondary
      objectives were to evaluate how many published RCTs had been registered and how
      many registered RCTs had resulted in a publication, using a sample of trials from
      the Netherlands Trials Register (NTR). DESIGN, SETTING: TWO DIFFERENT SAMPLES OF
      RCTS WERE EXAMINED: 1) RCTs published in November 2010 in core clinical journals
      identified in MEDLINE; 2) RCTs registered in the NTR with a latest expected end
      date of 31 August 2008. RESULTS: Fifty-five percent (166/302) of the reports of
      RCTs found in MEDLINE and 60% (186/312) of the published reports of RCTs from the
      NTR cohort contained a TRN. In both samples, reporting of a TRN was more likely
      in RCTs published in ICMJE member journals as compared to non-ICMJE member
      journals (MEDLINE 58% vs. 45%; NTR: 70% vs. 49%). Thirty-nine percent of
      published RCTs in the MEDLINE sample appear not to have been registered, and 48%
      of RCTs registered in the NTR seemed not to have been published at least two
      years after the expected date for study completion. CONCLUSION: Our results show
      that further promotion and implementation of trial registration and accurate
      reporting of TRN is still needed. This might be helped by inclusion of the TRN as
      an item on the CONSORT checklist.

PMID- 23166725
TI  - Ferocious fighting between male grasshoppers.
AB  - Contests among individuals over mating opportunities are common across diverse
      taxa, yet physical conflict is relatively rare. Due to the potentially fatal
      consequences of physical fighting, most animals employ mechanisms of conflict
      resolution involving signalling and ritualistic assessment. Here we provide the
      first evidence of ubiquitous escalated fighting in grasshoppers. The chameleon
      grasshopper (Kosciuscola tristis) is an Australian alpine specialist, in which
      males engage in highly aggressive combat over ovipositing females. We describe
      discrete agonistic behaviours including mandible flaring, mounting, grappling,
      kicking and biting, and their use depending on the individual's role as
      challenger or defender. We show that male role predicts damage, with challengers
      being more heavily damaged than males defending females (defenders). Challengers
      also possess wider mandibles than defenders, but are similar in other metrics of
      body size. Our data suggest that fights escalate between males matched in body
      size and that mandibles are used as weapons in this species. This system
      represents an exciting opportunity for future research into the evolution of
      costly fighting behaviour in an otherwise placid group.

PMID- 23166726
TI  - Use of four next-generation sequencing platforms to determine HIV-1 coreceptor
      tropism.
AB  - HIV-1 coreceptor tropism assays are required to rule out the presence of CXCR4
      tropic (non-R5) viruses prior treatment with CCR5 antagonists. Phenotypic (e.g.,
      TrofileTM, Monogram Biosciences) and genotypic (e.g., population sequencing
      linked to bioinformatic algorithms) assays are the most widely used. Although
      several next-generation sequencing (NGS) platforms are available, to date all
      published deep sequencing HIV-1 tropism studies have used the 454TM Life
      Sciences/Roche platform. In this study, HIV-1 co-receptor usage was predicted for
      twelve patients scheduled to start a maraviroc-based antiretroviral regimen. The
      V3 region of the HIV-1 env gene was sequenced using four NGS platforms: 454TM,
      PacBio(r) RS (Pacific Biosciences), Illumina(r), and Ion TorrentTM (Life
      Technologies). Cross-platform variation was evaluated, including number of reads,
      read length and error rates. HIV-1 tropism was inferred using Geno2Pheno, Web
      PSSM, and the 11/24/25 rule and compared with TrofileTM and virologic response to
      antiretroviral therapy. Error rates related to insertions/deletions (indels) and
      nucleotide substitutions introduced by the four NGS platforms were low compared
      to the actual HIV-1 sequence variation. Each platform detected all major virus
      variants within the HIV-1 population with similar frequencies. Identification of
      non-R5 viruses was comparable among the four platforms, with minor differences
      attributable to the algorithms used to infer HIV-1 tropism. All NGS platforms
      showed similar concordance with virologic response to the maraviroc-based regimen
      (75% to 80% range depending on the algorithm used), compared to Trofile (80%) and
      population sequencing (70%). In conclusion, all four NGS platforms were able to
      detect minority non-R5 variants at comparable levels suggesting that any NGS
      based method can be used to predict HIV-1 coreceptor usage.

PMID- 23166727
TI  - An enhanced immune response of Mclk1+/- mutant mice is associated with partial
      protection from fibrosis, cancer and the development of biomarkers of aging.
AB  - The immune response is essential for survival by destroying microorganisms and
      pre-cancerous cells. However, inflammation, one aspect of this response, can
      result in short- and long-term deleterious side-effects. Mclk1+/- mutant mice can
      be long-lived despite displaying a hair-trigger inflammatory response and
      chronically activated macrophages as a result of high mitochondrial ROS
      generation. Here we ask whether this phenotype is beneficial or simply tolerated.
      We used models of infection by Salmonella serovars and found that Mclk1+/-
      mutants mount a stronger immune response, control bacterial proliferation better,
      and are resistant to cell and tissue damage resulting from the response,
      including fibrosis and types of oxidative damage that are considered to be
      biomarkers of aging. Moreover, these same types of tissue damage were found to be
      low in untreated 23 months-old mutants. We also examined the initiation of tumour
      growth after transplantation of mouse LLC1 carcinoma cells into Mclk1+/- mutants,
      as well as during spontaneous tumorigenesis in Mclk1+/-Trp53+/- double mutants.
      Tumour latency was increased by the Mclk1+/- genotype in both models.
      Furthermore, we used the transplantation model to show that splenic CD8+ T
      lymphocytes from Mclk1+/- graft recipients show enhanced cytotoxicity against
      LLC1 cells in vitro. Mclk1+/- mutants thus display an association of an enhanced
      immune response with partial protection from age-dependent processes and from
      pathologies similar to those that are found with increased frequency during the
      aging process. This suggests that the immune phenotype of these mutants might
      contribute to their longevity. We discuss how these findings suggest a broader
      view of how the immune response might impact the aging process.

PMID- 23166728
TI  - CryoEM visualization of an adenovirus capsid-incorporated HIV antigen.
AB  - Adenoviral (Ad) vectors show promise as platforms for vaccine applications
      against infectious diseases including HIV. However, the requirements for
      eliciting protective neutralizing antibody and cellular immune responses against
      HIV remain a major challenge. In a novel approach to generate 2F5- and 4E10-like
      antibodies, we engineered an Ad vector with the HIV membrane proximal ectodomain
      region (MPER) epitope displayed on the hypervariable region 2 (HVR2) of the viral
      hexon capsid, instead of expressed as a transgene. The structure and flexibility
      of MPER epitopes, and the structural context of these epitopes within viral
      vectors, play important roles in the induced host immune responses. In this
      regard, understanding the critical factors for epitope presentation would
      facilitate optimization strategies for developing viral vaccine vectors.
      Therefore we undertook a cryoEM structural study of this Ad vector, which was
      previously shown to elicit MPER-specific humoral immune responses. A subnanometer
      resolution cryoEM structure was analyzed with guided molecular dynamics
      simulations. Due to the arrangement of hexons within the Ad capsid, there are
      twelve unique environments for the inserted peptide that lead to a variety of
      conformations for MPER, including individual alpha-helices, interacting alpha
      helices, and partially extended forms. This finding is consistent with the known
      conformational flexibility of MPER. The presence of an extended form, or an
      induced extended form, is supported by interaction of this vector with the human
      HIV monoclonal antibody 2F5, which recognizes 14 extended amino acids within
      MPER. These results demonstrate that the Ad capsid influences epitope structure,
      flexibility and accessibility, all of which affect the host immune response. In
      summary, this cryoEM structural study provided a means to visualize an epitope
      presented on an engineered viral vector and suggested modifications for the next
      generation of Ad vectors with capsid-incorporated HIV epitopes.

PMID- 23166729
TI  - In bonobos yawn contagion is higher among kin and friends.
AB  - In humans, the distribution of yawn contagion is shaped by social closeness with
      strongly bonded pairs showing higher levels of contagion than weakly bonded
      pairs. This ethological finding led the authors to hypothesize that the
      phenomenon of yawn contagion may be the result of certain empathic abilities,
      although in their most basal form. Here, for the first time, we show the capacity
      of bonobos (Pan paniscus) to respond to yawns of conspecifics. Bonobos
      spontaneously yawned more frequently during resting/relaxing compared to social
      tension periods. The results show that yawn contagion was context independent
      suggesting that the probability of yawning after observing others' yawns is not
      affected by the propensity to engage in spontaneous yawns. As it occurs in
      humans, in bonobos the yawing response mostly occurred within the first minute
      after the perception of the stimulus. Finally, via a Linear Mixed Model we tested
      the effect of different variables (e.g., sex, rank, relationship quality) on yawn
      contagion, which increased when subjects were strongly bonded and when the
      triggering subject was a female. The importance of social bonding in shaping yawn
      contagion in bonobos, as it occurs in humans, is consistent with the hypothesis
      that empathy may play a role in the modulation of this phenomenon in both
      species. The higher frequency of yawn contagion in presence of a female as a
      triggering subject supports the hypothesis that adult females not only represent
      the relational and decisional nucleus of the bonobo society, but also that they
      play a key role in affecting the emotional states of others.

PMID- 23166730
TI  - Amyloid beta levels in human red blood cells.
AB  - Amyloid beta-peptide (Abeta) is hypothesized to play a key role by oxidatively
      impairing the capacity of red blood cells (RBCs) to deliver oxygen to the brain.
      These processes are implicated in the pathogenesis of Alzheimer's disease (AD).
      Although plasma Abeta has been investigated thoroughly, the presence and
      distribution of Abeta in human RBCs are still unclear. In this study, we
      quantitated Abeta40 and Abeta42 in human RBCs with ELISA assays, and provided
      evidence that significant amounts of Abeta could be detected in RBCs and that the
      RBC Abeta levels increased with aging. The RBC Abeta levels increased with aging.
      On the other hand, providing an antioxidant supplement (astaxanthin, a polar
      carotenoid) to humans was found to decrease RBC Abeta as well as oxidative stress
      marker levels. These results suggest that plasma Abeta40 and Abeta42 bind to RBCs
      (possibly with aging), implying a pathogenic role of RBC Abeta. Moreover, the
      data indicate that RBC Abeta40 and Abeta42 may constitute biomarkers of AD. As a
      preventive strategy, therapeutic application of astaxanthin as an Abeta-lowering
      agent in RBCs could be considered as a possible anti-dementia agent. TRIAL
      REGISTRATION: Controlled-Trials.com ISRCTN42483402.

PMID- 23166731
TI  - Outer membrane protein A (OmpA): a new player in shigella flexneri protrusion
      formation and inter-cellular spreading.
AB  - Outer membrane protein A (OmpA) is a multifaceted predominant outer membrane
      protein of Escherichia coli and other Enterobacteriaceae whose role in the
      pathogenesis of various bacterial infections has recently been recognized. Here,
      the role of OmpA on the virulence of Shigella flexneri has been investigated. An
      ompA mutant of wild-type S. flexneri 5a strain M90T was constructed (strain
      HND92) and it was shown to be severely impaired in cell-to-cell spreading since
      it failed to plaque on HeLa cell monolayers. The lack of OmpA significantly
      reduced the levels of IcsA while the levels of cell associated and released IcsP
      cleaved 95 kDa amino-terminal portion of the mature protein were similar.
      Nevertheless, the ompA mutant displayed IcsA exposed across the entire bacterial
      surface. Surprisingly, the ompA mutant produced proper F-actin comet tails,
      indicating that the aberrant IcsA exposition at bacterial lateral surface did not
      affect proper activation of actin-nucleating proteins, suggesting that the
      absence of OmpA likely unmasks mature or cell associated IcsA at bacterial
      lateral surface. Moreover, the ompA mutant was able to invade and to multiply
      within HeLa cell monolayers, although internalized bacteria were found to be
      entrapped within the host cell cytoplasm. We found that the ompA mutant produced
      significantly less protrusions than the wild-type strain, indicating that this
      defect could be responsible of its inability to plaque. Although we could not
      definitely rule out that the ompA mutation might exert pleiotropic effects on
      other S. flexneri genes, complementation of the ompA mutation with a recombinant
      plasmid carrying the S. flexneri ompA gene clearly indicated that a functional
      OmpA protein is required and sufficient for proper IcsA exposition, plaque and
      protrusion formation. Moreover, an independent ompA mutant was generated. Since
      we found that both mutants displayed identical virulence profile, these results
      further supported the findings presented in this study.

PMID- 23166732
TI  - The Sec1/Munc18 protein Vps45 regulates cellular levels of its SNARE binding
      partners Tlg2 and Snc2 in Saccharomyces cerevisiae.
AB  - Intracellular membrane trafficking pathways must be tightly regulated to ensure
      proper functioning of all eukaryotic cells. Central to membrane trafficking is
      the formation of specific SNARE (soluble N-ethylmeleimide-sensitive factor
      attachment protein receptor) complexes between proteins on opposing lipid
      bilayers. The Sec1/Munc18 (SM) family of proteins play an essential role in SNARE
      mediated membrane fusion, and like the SNAREs are conserved through evolution
      from yeast to humans. The SM protein Vps45 is required for the formation of yeast
      endosomal SNARE complexes and is thus essential for traffic through the endosomal
      system. Here we report that, in addition to its role in regulating SNARE complex
      assembly, Vps45 regulates cellular levels of its SNARE binding partners: the
      syntaxin Tlg2 and the v-SNARE Snc2: Cells lacking Vps45 have reduced cellular
      levels of Tlg2 and Snc2; and elevation of Vps45 levels results in concomitant
      increases in the levels of both Tlg2 and Snc2. As well as regulating traffic
      through the endosomal system, the Snc v-SNAREs are also required for exocytosis.
      Unlike most vps mutants, cells lacking Vps45 display multiple growth phenotypes.
      Here we report that these can be reversed by selectively restoring Snc2 levels in
      vps45 mutant cells. Our data indicate that as well as functioning as part of the
      machinery that controls SNARE complex assembly, Vps45 also plays a key role in
      determining the levels of its cognate SNARE proteins; another key factor in
      regulation of membrane traffic.

PMID- 23166733
TI  - The human cytomegalovirus DNA polymerase processivity factor UL44 is modified by
      SUMO in a DNA-dependent manner.
AB  - During the replication of human cytomegalovirus (HCMV) genome, the viral DNA
      polymerase subunit UL44 plays a key role, as by binding both DNA and the
      polymerase catalytic subunit it confers processivity to the holoenzyme. However,
      several lines of evidence suggest that UL44 might have additional roles during
      virus life cycle. To shed light on this, we searched for cellular partners of
      UL44 by yeast two-hybrid screenings. Intriguingly, we discovered the interaction
      of UL44 with Ubc9, an enzyme involved in the covalent conjugation of SUMO (Small
      Ubiquitin-related MOdifier) to cellular and viral proteins. We found that UL44
      can be extensively sumoylated not only in a cell-free system and in transfected
      cells, but also in HCMV-infected cells, in which about 50% of the protein
      resulted to be modified at late times post-infection, when viral genome
      replication is accomplished. Mass spectrometry studies revealed that UL44
      possesses multiple SUMO target sites, located throughout the protein. Remarkably,
      we observed that binding of UL44 to DNA greatly stimulates its sumoylation both
      in vitro and in vivo. In addition, we showed that overexpression of SUMO alters
      the intranuclear distribution of UL44 in HCMV-infected cells, and enhances both
      virus production and DNA replication, arguing for an important role for
      sumoylation in HCMV life cycle and UL44 function(s). These data report for the
      first time the sumoylation of a viral processivity factor and show that there is
      a functional interplay between the HCMV UL44 protein and the cellular sumoylation
      system.

PMID- 23166734
TI  - CD95 is part of a let-7/p53/miR-34 regulatory network.
AB  - The death receptor CD95 (APO-1/Fas) mediates apoptosis induction upon ligation by
      its cognate ligand CD95L. Two types of CD95 signaling pathways have been
      identified, which are characterized by the absence (Type I) or presence (Type II)
      of mitochondrial involvement. Micro(mi)RNAs are small noncoding RNAs that
      negatively regulate gene expression. They are important regulators of
      differentiation processes and are found frequently deregulated in many human
      cancers. We recently showed that Type I cells express less of the differentiation
      marker miRNA let-7 and, hence, likely represent more advanced tumor cells than
      the let-7 high expressing Type II cells. We have now identified miR-34a as a
      selective marker for cells that are sensitive to CD95-mediated apoptosis. Both
      CD95 and miR-34a are p53 target genes, and consequently, both the sensitivity of
      cancer cells to CD95-mediated apoptosis and the ability to respond to p53
      mediated DNA genotoxic stress are linked. Interestingly, while miR-34a was found
      to positively correlate with the ability of cells to respond to genotoxic stress,
      let-7 was negatively correlated. The expression level of CD95 inversely
      correlated with the expression of let-7 suggesting regulation of let-7 expression
      by CD95. To test a link between p53 and miR-34a, we altered the expression of
      CD95. This affected the ability of cells to activate p53 and to regulate miR-34a.
      Our data point to a novel regulatory network comprising p53, CD95, let-7, and miR
      34a that affects cancer cell survival, differentiation, and sensitivity to
      apoptotic signals. The possible relevance of this regulatory network for cancer
      stem cells is discussed.

PMID- 23166735
TI  - Bidirectional scaling of astrocytic metabotropic glutamate receptor signaling
      following long-term changes in neuronal firing rates.
AB  - Very little is known about the ability of astrocytic receptors to exhibit
      plasticity as a result of changes in neuronal activity. Here we provide evidence
      for bidirectional scaling of astrocytic group I metabotropic glutamate receptor
      signaling in acute mouse hippocampal slices following long-term changes in
      neuronal firing rates. Plasticity of astrocytic mGluRs was measured by recording
      spontaneous and evoked Ca2+ elevations in both astrocytic somata and processes.
      An exogenous astrocytic Gq G protein-coupled receptor was resistant to scaling,
      suggesting that the alterations in astrocyte Ca2+ signaling result from changes
      in activity of the surface mGluRs rather than a change in intracellular G protein
      signaling molecules. These findings suggest that astrocytes actively detect
      shifts in neuronal firing rates and adjust their receptor signaling accordingly.
      This type of long-term plasticity in astrocytes resembles neuronal homeostatic
      plasticity and might be important to ensure an optimal or expected level of input
      from neurons.

PMID- 23166736
TI  - Mitochondrial DNA mutations provoke dominant inhibition of mitochondrial inner
      membrane fusion.
AB  - Mitochondria are highly dynamic organelles that continuously move, fuse and
      divide. Mitochondrial dynamics modulate overall mitochondrial morphology and are
      essential for the proper function, maintenance and transmission of mitochondria
      and mitochondrial DNA (mtDNA). We have investigated mitochondrial fusion in yeast
      cells with severe defects in oxidative phosphorylation (OXPHOS) due to removal or
      various specific mutations of mtDNA. We find that, under fermentative conditions,
      OXPHOS deficient cells maintain normal levels of cellular ATP and ADP but display
      a reduced mitochondrial inner membrane potential. We demonstrate that, despite
      metabolic compensation by glycolysis, OXPHOS defects are associated to a
      selective inhibition of inner but not outer membrane fusion. Fusion inhibition
      was dominant and hampered the fusion of mutant mitochondria with wild-type
      mitochondria. Inhibition of inner membrane fusion was not systematically
      associated to changes of mitochondrial distribution and morphology, nor to
      changes in the isoform pattern of Mgm1, the major fusion factor of the inner
      membrane. However, inhibition of inner membrane fusion correlated with specific
      alterations of mitochondrial ultrastructure, notably with the presence of aligned
      and unfused inner membranes that are connected to two mitochondrial boundaries.
      The fusion inhibition observed upon deletion of OXPHOS related genes or upon
      removal of the entire mtDNA was similar to that observed upon introduction of
      point mutations in the mitochondrial ATP6 gene that are associated to neurogenic
      ataxia and retinitis pigmentosa (NARP) or to maternally inherited Leigh Syndrome
      (MILS) in humans. Our findings indicate that the consequences of mtDNA mutations
      may not be limited to OXPHOS defects but may also include alterations in
      mitochondrial fusion. Our results further imply that, in healthy cells, the
      dominant inhibition of fusion could mediate the exclusion of OXPHOS-deficient
      mitochondria from the network of functional, fusogenic mitochondria.

PMID- 23166737
TI  - Quaternary structure heterogeneity of oligomeric proteins: a SAXS and SANS study
      of the dissociation products of Octopus vulgaris hemocyanin.
AB  - Octopus vulgaris hemocyanin shows a particular self-assembling pattern,
      characterized by a hierarchical organization of monomers. The highest molecular
      weight aggregate is a decamer, the stability of which in solution depends on
      several parameters. Different pH values, buffer compositions, H2O/D2O ratios and
      Hofmeister's salts result in modifications of the aggregation state of Octopus
      vulgaris hemocyanin. The new QUAFIT method, recently applied to derive the
      structure of the decameric and the monomeric assembly from small-angle scattering
      data, is used here to model the polydisperse system that results from changing
      the solution conditions. A dataset of small-angle X-rays and neutron scattering
      curves is analysed by QUAFIT to derive structure, composition and concentration
      of different assemblies present in solution. According to the hierarchy of the
      association/dissociation processes and the possible number of different
      aggregation products in solution, each sample has been considered as a
      heterogeneous mixture composed of the entire decamer, the dissociated "loose"
      monomer and all the intermediate dissociation products. Scattering curves
      corresponding to given experimental conditions are well fitted by using a linear
      combination of single particle form factors. QUAFIT has proved to be a method of
      general validity to describe solutions of proteins that, even after purification
      processes, result to be intrinsically heterogeneous.

PMID- 23166738
TI  - Adherence by Dutch public health nurses to the national guidelines for
      tuberculosis contact investigation.
AB  - OBJECTIVES: To assess whether public health nurses adhered to Dutch guidelines
      for tuberculosis contact investigations and to explore which factors influenced
      the process of identifying contacts, prioritizing contacts for testing and
      scaling up a contact investigation. METHODS: A multiple-case study (2010-2012)
      compared the contact investigation guidelines as recommended with their use in
      practice. We interviewed twice 14 public health nurses of seven Public Health
      Services while they conducted a contact investigation. RESULTS: We found more
      individuals to be identified as contacts than recommended, owing to a desire to
      gain insight into the infectiousness of the index case and prevent anxiety among
      potential contacts. Because some public health nurses did not believe the
      recommendations for prioritizing contacts fully encompassed daily practice, they
      preferred their own regular routine. In scaling up a contact investigation, they
      hardly applied the stone-in-the-pond principle. They neither regularly compared
      the infection prevalence in the contact investigation with the background
      prevalence in the community, especially not in immigrant populations.
      Nonadherence was related to ambiguity of the recommendations and a tendency to
      act from an individual health-care position rather than a population health
      perspective. CONCLUSIONS: The adherence to the contact investigation guidelines
      was limited, restraining the effectiveness, efficiency and uniformity of
      tuberculosis control. Adherence could be optimized by specifying guideline
      recommendations, actively involving the TB workforce, and training public health
      nurses.

PMID- 23166739
TI  - Evidence of Bacteroides fragilis protection from Bartonella henselae-induced
      damage.
AB  - Bartonella henselae is able to internalize endothelial progenitor cells (EPCs),
      which are resistant to the infection of other common pathogens. Bacteroides
      fragilis is a gram-negative anaerobe belonging to the gut microflora. It protects
      from experimental colitis induced by Helicobacter hepaticus through the
      polysaccharide A (PSA). The aim of our study was to establish: 1) whether B.
      fragilis colonization could protect from B. henselae infection; if this event may
      have beneficial effects on EPCs, vascular system and tissues. Our in vitro
      results establish for the first time that B. fragilis can internalize EPCs and
      competes with B. henselae during coinfection. We observed a marked activation of
      the inflammatory response by Real-time PCR and ELISA in coinfected cells compared
      to B. henselae-infected cells (63 vs 23 up-regulated genes), and after EPCs
      infection with mutant B. fragilis DeltaPSA (?90% up-regulated genes) compared to
      B. fragilis. Interestingly, in a mouse model of coinfection, morphological and
      ultrastructural analyses by hematoxylin-eosin staining and electron microscopy on
      murine tissues revealed that damages induced by B. henselae can be prevented in
      the coinfection with B. fragilis but not with its mutant B. fragilis DeltaPSA.
      Moreover, immunohistochemistry analysis with anti-Bartonella showed that the
      number of positive cells per field decreased of at least 50% in the liver (20+/-4
      vs 50+/-8), aorta (5+/-1 vs 10+/-2) and spleen (25+/-3 vs 40+/-6) sections of
      mice coinfected compared to mice infected only with B. henselae. This decrease
      was less evident in the coinfection with DeltaPSA strain (35+/-6 in the liver,
      5+/-1 in the aorta and 30+/-5 in the spleen). Finally, B. fragilis colonization
      was also able to restore the EPC decrease observed in mice infected with B.
      henselae (0.65 vs 0.06 media). Thus, our data establish that B. fragilis
      colonization is able to prevent B. henselae damages through PSA.

PMID- 23166740
TI  - Substance use disorders and adoption: findings from a national sample.
AB  - BACKGROUND: Prior research has shown that adoptees have a higher rate of
      substance use disorders (SUDs) than nonadoptees. But these findings have not been
      verified with a population-based sample of adult adoptees in the United States.
      Also, no previous adoption study has measured the prevalence of each specific
      substance use disorder (SUD). We aimed to compare lifetime prevalence rates and
      odds ratios of SUDs in adopted and nonadopted adults. METHODS AND FINDINGS: The
      data come from the National Epidemiologic Survey on Alcohol and Related
      Conditions (NESARC). The main outcome measure was the prevalence of lifetime SUDs
      in adopted (n = 378) and nonadopted adults (n = 42503). Adoptees and nonadoptees
      were compared to estimate the odds of lifetime SUDs using logistic regression
      analysis. Adoptees had higher prevalence rates of lifetime SUDs than nonadoptees.
      Overall, adoptees had a 1.87-fold increase (adjusted odds ratio [AOR] 1.87, 95%
      CI 1.51-2.31) in the odds of any lifetime SUD compared to nonadoptees. For each
      SUD, adoptees had higher odds for alcohol abuse/dependence (AOR 1.84), nicotine
      dependence (AOR 1.78), cannabis abuse/dependence (AOR 1.77), cocaine
      abuse/dependence (AOR 2.54), amphetamine abuse/dependence (AOR 3.14),
      hallucinogen abuse/dependence (AOR 2.85), opioid abuse/dependence (AOR 2.21), and
      other drug abuse/dependence (AOR 2.87) compared to nonadoptees. This study also
      identified two adoption-specific risk factors (Hispanic, never married)
      associated with any lifetime SUD. CONCLUSIONS: This study demonstrated an
      increased risk of lifetime SUDs in adopted adults. The findings can be useful for
      clinicians and policy makers to provide education, prevention, and support for
      adoptees and their families.

PMID- 23166741
TI  - Differential expression of in vivo and in vitro protein profile of outer membrane
      of Acidovorax avenae subsp. avenae.
AB  - Outer membrane (OM) proteins play a significant role in bacterial pathogenesis.
      In this work, we examined and compared the expression of the OM proteins of the
      rice pathogen Acidovorax avenae subsp. avenae strain RS-1, a Gram-negative
      bacterium, both in an in vitro culture medium and in vivo rice plants. Global
      proteomic profiling of A. avenae subsp. avenae strain RS-1 comparing in vivo and
      in vitro conditions revealed the differential expression of proteins affecting
      the survival and pathogenicity of the rice pathogen in host plants. The shotgun
      proteomics analysis of OM proteins resulted in the identification of 97 proteins
      in vitro and 62 proteins in vivo by mass spectrometry. Among these OM proteins,
      there is a high number of porins, TonB-dependent receptors, lipoproteins of the
      NodT family, ABC transporters, flagellins, and proteins of unknown function
      expressed under both conditions. However, the major proteins such as
      phospholipase and OmpA domain containing proteins were expressed in vitro, while
      the proteins such as the surface anchored protein F, ATP-dependent Clp protease,
      OmpA and MotB domain containing proteins were expressed in vivo. This may
      indicate that these in vivo OM proteins have roles in the pathogenicity of A.
      avenae subsp. avenae strain RS-1. In addition, the LC-MS/MS identification of
      OmpA and MotB validated the in silico prediction of the existance of Type VI
      secretion system core components. To the best of our knowledge, this is the first
      study to reveal the in vitro and in vivo protein profiles, in combination with LC
      MS/MS mass spectra, in silico OM proteome and in silico genome wide analysis, of
      pathogenicity or plant host required proteins of a plant pathogenic bacterium.

PMID- 23166742
TI  - Different location sampling frequencies by satellite tags yield different
      estimates of migration performance: pooling data requires a common protocol.
AB  - BACKGROUND: Migration research is in rapid expansion and increasingly based on
      sophisticated satellite-tracking devices subject to constant technological
      refinement, but is still ripe with descriptive studies and in need of meta
      analyses looking for emergent generalisations. In particular, coexistence of
      studies and devices with different frequency of location sampling and spatial
      accuracy generates doubts of data compatibility, potentially preventing meta
      analyses. We used satellite-tracking data on a migratory raptor to: (1) test
      whether data based on different location sampling frequencies and on different
      position subsampling approaches are compatible, and (2) seek potential solutions
      that enhance compatibility and enable eventual meta-analyses.
      METHODOLOGY/PRINCIPAL FINDINGS: We used linear mixed models to analyse the
      differences in the speed and route length of the migration tracks of 36 Black
      kites (Milvus migrans) satellite-tagged with two different types of devices
      (Argos vs GPS tags), entailing different regimes of position sampling frequency.
      We show that different location sampling frequencies and data subsampling
      approaches generate large (up to 33%) differences in the estimates of route
      length and migration speed of this migratory bird. CONCLUSIONS/SIGNIFICANCE: Our
      results show that the abundance of locations available for analysis affects the
      tortuosity and realism of the estimated migration path. To avoid flaws in future
      meta-analyses or unnecessary loss of data, we urge researchers to reach an
      agreement on a common protocol of data presentation, and to recognize that all
      transmitter-based studies are likely to underestimate the actual distance
      traveled by the marked animal. As ecological research becomes increasingly
      technological, new technologies should be matched with improvements in analytical
      capacity that guarantee data compatibility.

PMID- 23166743
TI  - How should we best estimate the mean recency duration for the BED method?
AB  - BED estimates of HIV incidence from cross-sectional surveys are obtained by
      restricting, to fixed time T, the period over which incidence is estimated. The
      appropriate mean recency duration (Omega(T)) then refers to the time where BED
      optical density (OD) is less than a pre-set cut-off C, given the patient has been
      HIV positive for at most time T. Five methods, tested using data for postpartum
      women in Zimbabwe, provided similar estimates of Omega(T) for C = 0.8: i) The
      ratio (r/s) of the number of BED-recent infections to all seroconversions over T
      = 365 days: 192 days [95% CI 168-216]. ii) Linear mixed modeling (LMM): 191 days
      [95% CI 174-208]. iii) Non-linear mixed modeling (NLMM): 196 days [95% CrI 188
      204]. iv) Survival analysis (SA): 192 days [95% CI 168-216]. Graphical analysis:
      193 days. NLMM estimates of Omega(T)--based on a biologically more appropriate
      functional relationship than LMM--resulted in best fits to OD data, the smallest
      variance in estimates of VT, and best correspondence between BED and follow-up
      estimates of HIV incidence, for the same subjects over the same time period. SA
      and NLMM produced very similar estimates of Omega(T) but the coefficient of
      variation of the former was .3 times as high. The r/s method requires uniformly
      distributed seroconversion events but is useful if data are available only from a
      single follow-up. The graphical method produces the most variable results,
      involves unsound methodology and should not be used to provide estimates of
      Omega(T). False-recent rates increased as a quadratic function of C: for
      incidence estimation C should thus be chosen as small as possible, consistent
      with an adequate resultant number of recent cases, and accurate estimation of
      Omega(T). Inaccuracies in the estimation of Omega(T) should not now provide an
      impediment to incidence estimation.

PMID- 23166744
TI  - A descriptive analysis of overviews of reviews published between 2000 and 2011.
AB  - BACKGROUND: Overviews of systematic reviews compile data from multiple systematic
      reviews (SRs) and are a new method of evidence synthesis. OBJECTIVES: To describe
      the methodological approaches in overviews of interventions. DESIGN: Descriptive
      study. METHODS: We searched 4 databases from 2000 to July 2011; we handsearched
      Evidence-based Child Health: A Cochrane Review Journal. We defined an overview as
      a study that: stated a clear objective; examined an intervention; used explicit
      methods to identify SRs; collected and synthesized outcome data from the SRs; and
      intended to include only SRs. We did not restrict inclusion by population
      characteristics (e.g., adult or children only). Two researchers independently
      screened studies and applied eligibility criteria. One researcher extracted data
      with verification by a second. We conducted a descriptive analysis. RESULTS: From
      2,245 citations, 75 overviews were included. The number of overviews increased
      from 1 in 2000 to 14 in 2010. The interventions were pharmacological (n = 20,
      26.7%), non-pharmacological (n = 26, 34.7%), or both (n = 29, 38.7%). Inclusion
      criteria were clearly stated in 65 overviews. Thirty-three (44%) overviews
      searched at least 2 databases. The majority reported the years and databases
      searched (n = 46, 61%), and provided key words (n = 58, 77%). Thirty-nine (52%)
      overviews included Cochrane SRs only. Two reviewers independently screened and
      completed full text review in 29 overviews (39%). Methods of data extraction were
      reported in 45 (60%). Information on quality of individual studies was extracted
      from the original SRs in 27 (36%) overviews. Quality assessment of the SRs was
      performed in 28 (37%) overviews; at least 9 different tools were used. Quality of
      the body of evidence was assessed in 13 (17%) overviews. Most overviews provided
      a narrative or descriptive analysis of the included SRs. One overview conducted
      indirect analyses and the other conducted mixed treatment comparisons.
      Publication bias was discussed in 18 (24%) overviews. CONCLUSIONS: This study
      shows considerable variation in the methods used for overviews. There is a need
      for methodological rigor and consistency in overviews, as well as empirical
      evidence to support the methods employed.

PMID- 23166745
TI  - Effects of a post-shock injection of the kappa opioid receptor antagonist
      norbinaltorphimine (norBNI) on fear and anxiety in rats.
AB  - Exposure of rats to footshocks leads to an enduring behavioral state involving
      generalized fear responses and avoidance. Recent evidence suggests that the
      expression of negative emotional behaviors produced by a stressor is in part
      mediated by dynorphin and its main receptor, the kappa opioid receptor (KOR). The
      purpose of this study was to determine if a subcutaneous injection of the long
      acting KOR antagonist norbinaltorphimine (norBNI; 15.0 and 30.0 mg/kg) given 2
      days after an acute exposure of rats to footshooks (5*2 s episodes of 1.5 mA
      delivered over 5 min) attenuates the expression of lasting fear and anxiety. We
      report that exposure of rats to acute footshock produced long-lasting (>4 weeks)
      fear (freezing) and anxiety (avoidance of an open area in the defensive
      withdrawal test). The 30 mg dose of norBNI attenuated the fear expressed when
      shock rats were placed in the shock context at Day 9 but not Day 27 post-shock.
      The same dose of norBNI had no effect on the expression of generalized fear
      produced when shock rats were placed in a novel chamber at Days 8 and 24. In
      contrast, the 30 mg dose of norBNI produced consistent anxiolytic effects in
      shock and nonshock rats. First, the 30 mg dose was found to decrease the latency
      to enter the open field in the defensive withdrawal test done 30 days after the
      shock exposure. Second, the same high dose also had anxiolytic effects in both
      nonshock and shock rats as evidence by a decrease in the mean time spent in the
      withdrawal box. The present study shows that systemic injection of the KOR
      antagonist norBNI had mixed effect on fear. In contrast, norBNI had an anxiolytic
      effect which included the attenuation of the enhanced avoidance of a novel area
      produced by a prior shock experience.

PMID- 23166746
TI  - Inflammatory cascades driven by tumor necrosis factor-alpha play a major role in
      the progression of acute liver failure and its neurological complications.
AB  - BACKGROUND/AIMS: Acute liver failure (ALF) due to ischemic or toxic liver injury
      is a clinical condition that results from massive loss of hepatocytes and may
      lead to hepatic encephalopathy (HE), a serious neuropsychiatric complication.
      Although increased expression of tumor necrosis factor-alpha (TNF-alpha) in
      liver, plasma and brain has been observed, conflicting results exist concerning
      its roles in drug-induced liver injury and on the progression of HE. The present
      study aimed to investigate the therapeutic value of etanercept, a TNF-alpha
      neutralizing molecule, on the progression of liver injury and HE in mice with ALF
      resulting from azoxymethane (AOM) hepatotoxicity. METHODS/PRINCIPAL FINDINGS:
      Mice were administered saline or etanercept (10 mg/kg; i.p.) 30 minutes prior to,
      or up to 6 h after AOM. Etanercept-treated ALF mice were sacrificed in parallel
      with vehicle-treated comatose ALF mice and controls. AOM induced severe hepatic
      necrosis, leading to HE, and etanercept administered prior or up to 3 h after AOM
      significantly delayed the onset of coma stages of HE. Etanercept pretreatment
      attenuated AOM-induced liver injury, as assessed by histological examination,
      plasma ammonia and transaminase levels, and by hepatic glutathione content.
      Peripheral inflammation was significantly reduced by etanercept as shown by
      decreased plasma IL-6 (4.1-fold; p<0.001) and CD40L levels (3.7-fold; p<0.001)
      compared to saline-treated ALF mice. Etanercept also decreased IL-6 levels in
      brain (1.2-fold; p<0.05), attenuated microglial activation (assessed by OX-42
      immunoreactivity), and increased brain glutathione concentrations. CONCLUSIONS:
      These results indicate that systemic sequestration of TNF-alpha attenuates both
      peripheral and cerebral inflammation leading to delayed progression of liver
      disease and HE in mice with ALF due to toxic liver injury. These results suggest
      that etanercept may provide a novel therapeutic approach for the management of
      ALF patients awaiting liver transplantation.

PMID- 23166747
TI  - Phylogenomic relationships between amylolytic enzymes from 85 strains of fungi.
AB  - Fungal amylolytic enzymes, including alpha-amylase, gluocoamylase and alpha
      glucosidase, have been extensively exploited in diverse industrial applications
      such as high fructose syrup production, paper making, food processing and ethanol
      production. In this paper, amylolytic genes of 85 strains of fungi from the phyla
      Ascomycota, Basidiomycota, Chytridiomycota and Zygomycota were annotated on the
      genomic scale according to the classification of glycoside hydrolase (GH) from
      the Carbohydrate-Active enZymes (CAZy) Database. Comparisons of gene abundance in
      the fungi suggested that the repertoire of amylolytic genes adapted to their
      respective lifestyles. Amylolytic enzymes in family GH13 were divided into four
      distinct clades identified as heterologous alpha-amylases, eukaryotic alpha
      amylases, bacterial and fungal alpha-amylases and GH13 alpha-glucosidases. Family
      GH15 had two branches, one for gluocoamylases, and the other with currently
      unknown function. GH31 alpha-glucosidases showed diverse branches consisting of
      neutral alpha-glucosidases, lysosomal acid alpha-glucosidases and a new clade
      phylogenetically related to the bacterial counterparts. Distribution of starch
      binding domains in above fungal amylolytic enzymes was related to the enzyme
      source and phylogeny. Finally, likely scenarios for the evolution of amylolytic
      enzymes in fungi based on phylogenetic analyses were proposed. Our results
      provide new insights into evolutionary relationships among subgroups of fungal
      amylolytic enzymes and fungal evolutionary adaptation to ecological conditions.

PMID- 23166748
TI  - A novel role of human holliday junction resolvase GEN1 in the maintenance of
      centrosome integrity.
AB  - The maintenance of genomic stability requires accurate genome replication, repair
      of DNA damage, and the precise segregation of chromosomes in mitosis. GEN1
      possesses Holliday junction resolvase activity in vitro and presumably functions
      in homology driven repair of DNA double strand breaks. However, little is
      currently known about the cellular functions of human GEN1. In the present study
      we demonstrate that GEN1 is a novel centrosome associated protein and we
      characterize the various phenotypes associated with GEN1 deficiency. We identify
      an N-terminal centrosome localization signal in GEN1, which is required and
      sufficient for centrosome localization. We report that GEN1 depletion results in
      aberrant centrosome numbers associated with the formation of multiple spindle
      poles in mitosis, an increased number of cells with multi-nuclei, increased
      apoptosis and an elevated level of spontaneous DNA damage. We find homologous
      recombination severely impaired in GEN1 deficient cells, suggesting that GEN1
      functions as a Holliday junction resolvase in vivo as well as in vitro.
      Complementation of GEN1 depleted cells with various GEN1 constructs revealed that
      centrosome association but not catalytic activity of GEN1 is required for
      preventing centrosome hyper-amplification, formation of multiple mitotic
      spindles, and multi-nucleation. Our findings provide novel insight into the
      biological functions of GEN1 by uncovering an important role of GEN1 in the
      regulation of centrosome integrity.

PMID- 23166750
TI  - A potential peptide therapeutic derived from the juxtamembrane domain of the
      epidermal growth factor receptor.
AB  - The epidermal growth factor receptor (EGFR) is involved in many cancers and EGFR
      has been heavily pursued as a drug target. Drugs targeting EGFR have shown
      promising clinical results for several cancer types. However, resistance to EGFR
      inhibitors often occurs, such as with KRAS mutant cancers, therefore new methods
      of targeting EGFR are needed. The juxtamembrane (JXM) domain of EGFR is critical
      for receptor activation and targeting this region could potentially be a new
      method of inhibiting EGFR. We hypothesized that the structural role of the JXM
      region could be mimicked by peptides encoding a JXM amino acid sequence, which
      could interfere with EGFR signaling and consequently could have anti-cancer
      activity. A peptide encoding EGFR 645-662 conjugated to the Tat sequence (TE
      64562) displayed anti-cancer activity in multiple human cancer cell types with
      diminished activity in non-EGFR expressing cells and non-cancerous cells. In nude
      mice, TE-64562 delayed MDA-MB-231 tumor growth and prolonged survival, without
      inducing toxicity. TE-64562 induced non-apoptotic cell death after several hours
      and caspase-3-mediated apoptotic cell death with longer treatment.
      Mechanistically, TE-64562 bound to EGFR, inhibited its dimerization and caused
      its down-regulation. TE-64562 reduced phosphorylated and total EGFR levels but
      did not inhibit kinase activity and instead prolonged it. Our analysis of patient
      data from The Cancer Genome Atlas supported the hypothesis that down-regulation
      of EGFR is a potential therapeutic strategy, since phospho- and total-EGFR levels
      were strongly correlated in a large majority of patient tumor samples, indicating
      that lower EGFR levels are associated with lower phospho-EGFR levels and
      presumably less proliferative signals in breast cancer. Akt and Erk were
      inhibited by TE-64562 and this inhibition was observed in vivo in tumor tissue
      upon treatment with TE-64562. These results are the first to indicate that the
      JXM domain of EGFR is a viable drug target for several cancer types.

PMID- 23166751
TI  - Live poultry trade in Southern China provinces and HPAIV H5N1 infection in humans
      and poultry: the role of Chinese New Year festivities.
AB  - BACKGROUND: The number of outbreaks of highly pathogenic avian influenza virus of
      the H5N1 subtype (HPAIV H5N1) over the past 5 years has been drastically reduced
      in China but sporadic infections in poultry and humans are still occurring. In
      this study, we aimed to investigate seasonal patterns in the association between
      the movement of live poultry originating from southern China and HPAIV H5N1
      infection history in humans and poultry in China. METHODOLOGY/PRINCIPAL FINDINGS:
      During January to April 2010, longitudinal questionnaire surveys were carried out
      monthly in four wholesale live bird markets (LBMs) in Hunan and Guangxi provinces
      of South China. Using social network analysis, we found an increase in the number
      of observed links and degree centrality between LBMs and poultry sources in
      February and March compared to the months of January and April. The association
      of some live poultry traders (LPT's) with a limited set of counties (within the
      catchment area of LBMs) in the months of February and March may support HPAIV
      H5N1 transmission and contribute to perpetuating HPAIV H5N1 virus circulation
      among certain groups of counties. The connectivity among counties experiencing
      human infection was significantly higher compared to counties without human
      infection for the months of January, March and April. Conversely, counties with
      poultry infections were found to be significantly less connected than counties
      without poultry infection for the month of February. CONCLUSIONS/SIGNIFICANCE:
      Our results show that temporal variation in live poultry trade in Southern China
      around the Chinese New Year festivities is associated with higher HPAIV H5N1
      infection risk in humans and poultry. This study has shown that capturing the
      dynamic nature of poultry trade networks in Southern China improves our ability
      to explain the spatiotemporal dissemination in avian influenza viruses in China.

PMID- 23166749
TI  - Paeoniflorin protects against ischemia-induced brain damages in rats via
      inhibiting MAPKs/NF-kappaB-mediated inflammatory responses.
AB  - Paeoniflorin (PF), the principal component of Paeoniae Radix prescribed in
      traditional Chinese medicine, has been reported to exhibit many pharmacological
      effects including protection against ischemic injury. However, the mechanisms
      underlying the protective effects of PF on cerebral ischemia are still under
      investigation. The present study showed that PF treatment for 14 days could
      significantly inhibit transient middle cerebral artery occlusion (MCAO)-induced
      over-activation of astrocytes and microglia, and prevented up-regulations of pro
      inflamamtory mediators (TNFalpha, IL-1beta, iNOS, COX(2) and 5-LOX) in plasma and
      brain. Further study demonstrated that chronic treatment with PF suppressed the
      activations of JNK and p38 MAPK, but enhanced ERK activation. And PF could
      reverse ischemia-induced activation of NF-kappaB signaling pathway. Moreover, our
      in vitro study revealed that PF treatment protected against TNFalpha-induced cell
      apoptosis and neuronal loss. Taken together, the present study demonstrates that
      PF produces a delayed protection in the ischemia-injured rats via inhibiting
      MAPKs/NF-kappaB mediated peripheral and cerebral inflammatory response. Our study
      reveals that PF might be a potential neuroprotective agent for stroke.

PMID- 23166752
TI  - Th17 effector cells support B cell responses outside of germinal centres.
AB  - Th17 cells are pro-inflammatory CD4+T cells, which are important in immune
      responses against fungal pathogens and extracellular bacteria and have also been
      implicated in various autoimmune syndromes. However, their role in supporting B
      cell responses in these scenarios remains unclear, representing a significant
      lapse in our understanding of the role Th17 play in vaccine responses and the
      regulation of autoimmunity. We employed T cell and B cell receptor transgenic
      mice specific for model antigens, and adoptive transfer approaches that allowed
      the tracking of cognate B and T cells in situ and ex vivo using immunological
      methods. We have found that T cells activated under Th17 polarising conditions
      have a greater capacity to provide cognate B cell help compared with Th1
      polarised populations, supporting higher expansion of antigen specific B cells
      and enhanced antibody titres. This advantage is associated with the increased
      persistence of Th17 polarised cells in areas of the lymph nodes where they can
      provide help (i.e. the B cell follicles). Also the Th17 cells are characterised
      by their higher expression of ICOS, a costimulatory molecule important for B cell
      help. Surprisingly, contrary to published reports, Th17 cells were not detected
      inside germinal centres, although they were found in close proximity to cognate B
      cells in the follicle early in the genesis of the humoral immune response. These
      data indicate that, Th17 cells have a more significant role earlier in the
      initiation/development of the germinal centre response and/or germinal centre
      independent events, consistent with their early effector status.

PMID- 23166753
TI  - An integrative computational framework based on a two-step random forest
      algorithm improves prediction of zinc-binding sites in proteins.
AB  - Zinc-binding proteins are the most abundant metalloproteins in the Protein Data
      Bank where the zinc ions usually have catalytic, regulatory or structural roles
      critical for the function of the protein. Accurate prediction of zinc-binding
      sites is not only useful for the inference of protein function but also important
      for the prediction of 3D structure. Here, we present a new integrative framework
      that combines multiple sequence and structural properties and graph-theoretic
      network features, followed by an efficient feature selection to improve
      prediction of zinc-binding sites. We investigate what information can be
      retrieved from the sequence, structure and network levels that is relevant to
      zinc-binding site prediction. We perform a two-step feature selection using
      random forest to remove redundant features and quantify the relative importance
      of the retrieved features. Benchmarking on a high-quality structural dataset
      containing 1,103 protein chains and 484 zinc-binding residues, our method
      achieved >80% recall at a precision of 75% for the zinc-binding residues Cys,
      His, Glu and Asp on 5-fold cross-validation tests, which is a 10%-28% higher
      recall at the 75% equal precision compared to SitePredict and zincfinder at
      residue level using the same dataset. The independent test also indicates that
      our method has achieved recall of 0.790 and 0.759 at residue and protein levels,
      respectively, which is a performance better than the other two methods. Moreover,
      AUC (the Area Under the Curve) and AURPC (the Area Under the Recall-Precision
      Curve) by our method are also respectively better than those of the other two
      methods. Our method can not only be applied to large-scale identification of zinc
      binding sites when structural information of the target is available, but also
      give valuable insights into important features arising from different levels that
      collectively characterize the zinc-binding sites. The scripts and datasets are
      available at http://protein.cau.edu.cn/zincidentifier/.

PMID- 23166754
TI  - A new way of assessing foraging behaviour at the individual level using faeces
      marking and satellite telemetry.
AB  - Heterogeneity in foraging behaviour can profoundly influence ecological processes
      shaping populations. To scale-up from individual foraging behaviour to processes
      occurring at the population scale, one needs to sample foraging behaviour at the
      individual level, and over large temporal scales or during critical seasons known
      to influence life-history traits. We developed an innovative technique to monitor
      foraging behaviour at the individual level in secretive species, a technique that
      can be ultimately used to investigate the links between foraging behaviour and
      life-history traits. First, the technique used a novel approach, namely the
      combination of telemetry tracking and biomarking of faeces with food dyes to
      locate fresh signs of presence left by individuals equipped with GPS collars.
      Second, the technique is based on the simultaneous or successive sampling of life
      history traits and individual foraging behaviour, using tracks with high
      probabilities of recovery of dyed faeces. We first describe our methodological
      approach, using a case study of a large herbivore, and then provide
      recommendations and guidelines for its use. Sampling single snow tracks of
      individuals equipped with a GPS collar was a reliable way to assess individual
      winter foraging behaviour in a white-tailed deer (Odocoileus virginianus
      Zimmermann) population. During that period, the probability of recovery of dyed
      faeces within the range of the collar precision was very high for single snow
      tracks of equipped deer (97%). Our approach is well suited to study individual
      foraging behaviour, and could ultimately be used to investigate the interplay
      between intra-population heterogeneity in foraging behaviour, life-history
      traits, and demographic processes.

PMID- 23166756
TI  - Biogeographical boundaries, functional group structure and diversity of Rocky
      Shore communities along the Argentinean coast.
AB  - We investigate the extent to which functional structure and spatial variability
      of intertidal communities coincide with major biogeographical boundaries, areas
      where extensive compositional changes in the biota are observed over a limited
      geographic extension. We then investigate whether spatial variation in the
      biomass of functional groups, over geographic (10's km) and local (10's m)
      scales, could be associated to species diversity within and among these groups.
      Functional community structure expressed as abundance (density, cover and
      biomass) and composition of major functional groups was quantified through field
      surveys at 20 rocky intertidal shores spanning six degrees of latitude along the
      southwest Atlantic coast of Argentina and extending across the boundaries between
      the Argentinean and Magellanic Provinces. Patterns of abundance of individual
      functional groups were not uniformly matched with biogeographical regions. Only
      ephemeral algae showed an abrupt geographical discontinuity coincident with
      changes in biogeographic boundaries, and this was limited to the mid intertidal
      zone. We identified 3-4 main 'groups' of sites in terms of the total and relative
      abundance of the major functional groups, but these did not coincide with
      biogeographical boundaries, nor did they follow latitudinal arrangement. Thus,
      processes that determine the functional structure of these intertidal communities
      are insensitive to biogeographical boundaries. Over both geographical and local
      spatial scales, and for most functional groups and tidal levels, increases in
      species richness within the functional group was significantly associated to
      increased total biomass and reduced spatial variability of the group. These
      results suggest that species belonging to the same functional group are
      sufficiently uncorrelated over space (i.e. metres and site-to-site ) to stabilize
      patterns of biomass variability and, in this manner, provide a buffer, or
      "insurance", against spatial variability in environmental conditions.

PMID- 23166755
TI  - Activated human T cells secrete exosomes that participate in IL-2 mediated immune
      response signaling.
AB  - It has previously been shown that nano-meter sized vesicles (30-100 nm),
      exosomes, secreted by antigen presenting cells can induce T cell responses thus
      showing the potential of exosomes to be used as immunological tools.
      Additionally, activated CD3+ T cells can secrete exosomes that have the ability
      to modulate different immunological responses. Here, we investigated what effects
      exosomes originating from activated CD3+ T cells have on resting CD3+ T cells by
      studying T cell proliferation, cytokine production and by performing T cell and
      exosome phenotype characterization. Human exosomes were generated in vitro
      following CD3+ T cell stimulation with anti-CD28, anti-CD3 and IL-2. Our results
      show that exosomes purified from stimulated CD3+ T cells together with IL-2 were
      able to generate proliferation in autologous resting CD3+ T cells. The CD3+ T
      cells stimulated with exosomes together with IL-2 had a higher proportion of CD8+
      T cells and had a different cytokine profile compared to controls. These results
      indicate that activated CD3+ T cells communicate with resting autologous T cells
      via exosomes.

PMID- 23166757
TI  - Molecular mimics of the tumour antigen MUC1.
AB  - A key requirement for the development of cancer immunotherapy is the
      identification of tumour-associated antigens that are differentially or
      exclusively expressed on the tumour and recognized by the host immune system.
      However, immune responses to such antigens are often muted or lacking due to the
      antigens being recognized as "self", and further complicated by the tumour
      environment and regulation of immune cells within. In an effort to circumvent the
      lack of immune responses to tumour antigens, we have devised a strategy to
      develop potential synthetic immunogens. The strategy, termed mirror image phage
      display, is based on the concept of molecular mimicry as demonstrated by the
      idiotype/anti-idiotype paradigm in the immune system. Here as 'proof of
      principle' we have selected molecular mimics of the well-characterised tumour
      associated antigen, the human mucin1 protein (MUC1) from two different peptide
      phage display libraries. The putative mimics were compared in structure and
      function to that of the native antigen. Our results demonstrate that several of
      the mimic peptides display T-cell stimulation activity in vitro when presented by
      matured dendritic cells. The mimic peptides and the native MUC1 antigenic
      epitopes can cross-stimulate T-cells. The data also indicate that sequence
      homology and/or chemical properties to the original epitope are not the sole
      determining factors for the observed immunostimulatory activity of the mimic
      peptides.

PMID- 23166758
TI  - Disease-dependent local IL-10 production ameliorates collagen induced arthritis
      in mice.
AB  - Rheumatoid arthritis (RA) is a chronic destructive autoimmune disease
      characterised by periods of flare and remission. Today's treatment is based on
      continuous immunosuppression irrespective of the patient's inflammatory status.
      When the disease is in remission the therapy is withdrawn but withdrawal attempts
      often results in inflammatory flares, and re-start of the therapy is commenced
      when the inflammation again is prominent which leads both to suffering and
      increased risk of tissue destruction. An attractive alternative treatment would
      provide a disease-regulated therapy that offers increased anti-inflammatory
      effect during flares and is inactive during periods of remission. To explore this
      concept we expressed the immunoregulatory cytokine interleukin (IL)-10 gene under
      the control of an inflammation dependent promoter in a mouse model of RA -
      collagen type II (CII) induced arthritis (CIA). Haematopoetic stem cells (HSCs)
      were transduced with lentiviral particles encoding the IL-10 gene (LNT-IL-10), or
      a green fluorescence protein (GFP) as control gene (LNT-GFP), driven by the
      inflammation-dependent IL-1/IL-6 promoter. Twelve weeks after transplantation of
      transduced HSCs into DBA/1 mice, CIA was induced. We found that LNT-IL-10 mice
      developed a reduced severity of arthritis compared to controls. The LNT-IL-10
      mice exhibited both increased mRNA expression levels of IL-10 as well as
      increased amount of IL-10 produced by B cells and non-B APCs locally in the lymph
      nodes compared to controls. These findings were accompanied by increased mRNA
      expression of the IL-10 induced suppressor of cytokine signalling 1 (SOCS1) in
      lymph nodes and a decrease in the serum protein levels of IL-6. We also found a
      decrease in both frequency and number of B cells and serum levels of anti-CII
      antibodies. Thus, inflammation-dependent IL-10 therapy suppresses experimental
      autoimmune arthritis and is a promising candidate in the development of novel
      treatments for RA.

PMID- 23166759
TI  - Sexual dimorphism in Sturnira lilium (Chiroptera, Phyllostomidae): can pregnancy
      and pup carrying be responsible for differences in wing shape?
AB  - Competition is one of the most cited mechanisms to explain secondary sexual
      dimorphism in animals. Nonetheless, it has been proposed that sexual dimorphism
      in bat wings is also a result of adaptive pressures to compensate additional
      weight caused by fetus or pup carrying during the reproductive period of females.
      The main objective of this study is to verify the existence of sexual dimorphism
      in Sturnira lilium wings. We employed geometric morphometrics techniques using
      anatomical landmarks superimposition to obtain size (Centroid Size) and shape
      variables of wings, which were reduced by Linear Discriminant Analysis (LDA). We
      also employed classical morphometrics using wing length measurements to compare
      efficiency between these two morphometric approaches and make comparisons using
      wing area measurements. LDA indicated significant differences between wing shapes
      of males and females, with 91% (stepwise classification) and 80% (leave-one-out
      cross validation) of correct classification. However, the size variable obtained
      did not contribute to such classifications. We have observed larger areas in
      female wings, but we found no differences in wing length measurements and no
      allometric effects in wing length, shape and area measurements. Interestingly,
      our study has provided evidences of morphological differences where classical
      morphometrics have failed. LDA and area measurements analyses revealed that
      females have a different area distribution in distinct portions of the wing, with
      wider dactylopatagia and plagiopatagia, and wingtips more triangular than males.
      No differences in body length or relative wing length were observed between the
      sexes, but pregnant females have more body weight than non-pregnant females and
      males. Our findings suggest that sexual dimorphism in the wing shape of S. lilium
      is probably related to the increase in flight efficiency of females during
      reproductive period. It decreases wing loading in specific portions of the wing
      and reduces energy cost to maintain a faster and maneuverable flight.

PMID- 23166760
TI  - Lack of genetic structure and female-specific effect of dispersal barriers in a
      rabies vector, the striped skunk (Mephitis mephitis).
AB  - Evaluating the permeability of potential barriers to movement, dispersal and gene
      exchanges can help describe spreading patterns of wildlife diseases. Here, we
      used landscape genetics methods to assess the genetic structure of the striped
      skunk (Mephitis mephitis), which is a frequent vector of rabies, a lethal
      zoonosis of great concern for public health. Our main objective was to identify
      landscape elements shaping the genetic structure of this species in Southern
      Quebec, Canada, in an area where the raccoon rabies variant has been detected. We
      hypothesised that geographic distance and landscape barriers, such as highways
      and major rivers, would modulate genetic structure. We genotyped a total of 289
      individuals sampled across a large area (22,000 km2) at nice microsatellite loci.
      Genetic structure analyses identified a single genetic cluster in the study area.
      Major rivers and highways, however, influenced the genetic relatedness among
      sampled individuals. Sex-specific analyses revealed that rivers significantly
      limited dispersal only for females while highways only had marginal effects.
      Rivers and highways did not significantly affect male dispersal. These results
      support the contention that female skunks are more philopatric than males.
      Overall, our results suggest that the effects of major rivers and highways on
      dispersal are sex-specific and rather weak and are thus unlikely to prevent the
      spread of rabies within and among striped skunk populations.

PMID- 23166761
TI  - Dietary n-3 polyunsaturated fatty acids (PUFA) decrease obesity-associated Th17
      cell-mediated inflammation during colitis.
AB  - Clinical and experimental evidence suggests that obesity-associated inflammation
      increases disease activity during colitis, attributed in part to the effects of
      Th17 cells. Using a model of concurrent obesity and colitis, we monitored changes
      in critical immune cell subsets and inflammatory biomarker expression in three
      key tissues: visceral adipose tissue, colon (local inflammatory site) and spleen
      (systemic inflammatory site), and we hypothesized that n-3 PUFA would reduce the
      percentage of inflammatory immune cell subsets and suppress inflammatory gene
      expression, thereby improving the disease phenotype. Obesity was induced in
      C57BL/6 mice by feeding a high fat (HF) diet (59.2% kcal) alone or an isocaloric
      HF diet supplemented with fish oil (HF-FO) for 12 weeks. Colitis was induced via
      a 2.5% trinitrobenzene sulfonic acid (TNBS) enema. The HF-FO diet improved the
      obese phenotype by reducing i) serum hormone concentrations (leptin and
      resistin), ii) adipose tissue mRNA expression of inflammatory cytokines (MCP-1,
      IFNgamma, IL-6, IL17F and IL-21) and iii) total (F4/80+ CD11b+) and inflammatory
      adipose tissue M1 (F4/80+ CD11c+) macrophage content compared to HF (P<0.05). In
      addition, the HF-FO diet reduced both colitis-associated disease severity and
      colonic mRNA expression of the Th17 cell master transcription factor
      (RORgammatau) and critical cytokines (IL-6, IL-17A, IL-17F, IL-21, IL-23 and
      IFNgamma) versus HF (P<0.05). Compared to HF, the percentage of both splenic Th17
      and Th1 cells were reduced by the HF-FO group (P<0.05). Under ex vivo polarizing
      conditions, the percentage of HF-FO derived CD4+ T cells that reached Th17 cell
      effector status was suppressed (P = 0.05). Collectively, these results indicate
      that n-3 PUFA suppress Th1/Th17 cells and inflammatory macrophage subsets and
      reconfigure the inflammatory gene expression profile in diverse tissue sites in
      obese mice following the induction of colitis.

PMID- 23166762
TI  - MR neurography in ulnar neuropathy as surrogate parameter for the presence of
      disseminated neuropathy.
AB  - PURPOSE: Patients with ulnar neuropathy of unclear etiology occasionally present
      with lesion extension from elbow to upper arm level on MRI. This study
      investigated whether MRI thereby distinguishes multifocal neuropathy from focal
      compressive neuropathy at the elbow. METHODS: This prospective study was approved
      by the institutional ethics committee and written informed consent was obtained
      from all participants. 122 patients with ulnar mononeuropathy of undetermined
      localization and etiology by clinical and electrophysiological examination were
      assessed by MRI at upper arm and elbow level using T2-weighted fat-saturated
      sequences at 3T. Twenty-one patients were identified with proximal ulnar nerve
      lesions and evaluated for findings suggestive of disseminated neuropathy (i)
      subclinical lesions in other nerves, (ii) unfavorable outcome after previous
      decompressive elbow surgery, and (iii) subsequent diagnosis of inflammatory or
      other disseminated neuropathy. Two groups served as controls for quantitative
      analysis of nerve-to-muscle signal intensity ratios: 20 subjects with typical
      focal ulnar neuropathy at the elbow and 20 healthy subjects. RESULTS: In the
      group of 21 patients with proximal ulnar nerve lesion extension, T2-w ulnar nerve
      signal was significantly (p<0.001) higher at upper arm level than in both control
      groups. A cut-off value of 1.92 for maximum nerve-to-muscle signal intensity
      ratio was found to be sensitive (86%) and specific (100%) to discriminate this
      group. Ten patients (48%) exhibited additional T2-w lesions in the median and/or
      radial nerve. Another ten (48%) had previously undergone elbow surgery without
      satisfying outcome. Clinical follow-up was available in 15 (71%) and revealed
      definitive diagnoses of multifocal neuropathy of various etiologies in four
      patients. In another eight, diagnoses could not yet be considered definitive but
      were consistent with multifocal neuropathy. CONCLUSION: Proximal ulnar nerve T2
      lesions at upper arm level are detected by MRI and indicate the presence of a non
      focal disseminated neuropathy instead of a focal compressive neuropathy.

PMID- 23166763
TI  - Sulforaphane inhibits prostaglandin E2 synthesis by suppressing microsomal
      prostaglandin E synthase 1.
AB  - Sulforaphane (SFN) is a dietary cancer preventive with incompletely characterized
      mechanism(s) of cancer prevention. Since prostaglandin E2 (PGE2) promotes cancer
      progression, we hypothesized that SFN may block PGE2 synthesis in cancer cells.
      We found that SFN indeed blocked PGE2 production in human A549 cancer cells not
      by inhibiting COX-2, but rather by suppressing the expression of microsomal
      prostaglandin E synthase (mPGES-1), the enzyme that directly synthesizes PGE2. We
      identified the Hypoxia Inducible Factor 1 alpha (HIF-1alpha) as the target of SFN
      mediated mPGES-1 suppression. SFN suppressed HIF-1alpha protein expression and
      the presence of HIF-1alpha at the mPGES-1 promoter, resulting in reduced
      transcription of mPGES-1. Finally, SFN also reduced expression of mPGES-1 and
      PGE2 production in A549 xenograft tumors in mice. Together, these results point
      to the HIF-1alpha, mPGES-1 and PGE2 axis as a potential mediator of the anti
      cancer effects of SFN, and illustrate the potential of SFN for therapeutic
      control of cancer and inflammation. Harmful side effects in patients taking
      agents that target the more upstream COX-2 enzyme render the downstream target
      mPGES-1 a significant target for anti-inflammatory therapy. Thus, SFN could prove
      to be an important therapeutic approach to both cancer and inflammation.

PMID- 23166764
TI  - CpLEPA is critical for chloroplast protein synthesis under suboptimal conditions
      in Arabidopsis thaliana.
AB  - LEPA is one of the most conserved translation factors and is found from bacteria
      to higher plants. However, the physiological function of the chloroplast LEPA
      homolog in higher plants remains unknown. Herein, we demonstrate the
      physiological role of cpLEPA in enabling efficient photosynthesis in higher
      plants. The cplepa-1 mutant displays slightly high chlorophyll fluorescence and
      pale green phenotypes under normal growth conditions. The growth of the cplepa-1
      mutant is reduced when grown on soil, and greater reduction is observed under
      intense light illumination. Photosynthetic activity is impaired in the cplepa-1
      mutants, which is reflected in the decreased steady-state levels of chloroplast
      proteins. In vivo protein labeling experiments explained the decrease in the
      steady-state levels of chloroplast proteins. An abnormal association of the
      chloroplast-encoded mRNAs with ribosomes suggests that the protein synthesis
      deficiencies in cplepa-1 are due to defects in translation initiation in the
      chloroplasts. The cpLEPA protein appears to be an essential translation factor
      that promotes the efficiency of chloroplast protein synthesis.

PMID- 23166765
TI  - Climate, cattle rearing systems and African Animal Trypanosomosis risk in Burkina
      Faso.
AB  - BACKGROUND: In sub-Saharan countries infested by tsetse flies, African Animal
      Trypanosomosis (AAT) is considered as the main pathological constraint to cattle
      breeding. Africa has known a strong climatic change and its population was
      multiplied by four during the last half-century. The aim of this study was to
      characterize the impact of production practices and climate on tsetse occurrence
      and abundance, and the associated prevalence of AAT in Burkina Faso.
      METHODOLOGY/PRINCIPAL FINDINGS: Four sites were selected along a South-north
      transect of increasing aridity. The study combines parasitological and
      entomological surveys. For the parasitological aspect, blood samples were
      collected from 1,041 cattle selected through a stratified sampling procedure
      including location and livestock management system (long transhumance, short
      transhumance, sedentary). Parasitological and serological prevalence specific to
      livestock management systems show a gradual increase from the Sahelian to the
      Sudano-Guinean area (P<0.05). Livestock management system had also a significant
      impact on parasitological prevalence (P<0.05). Tsetse diversity, apparent
      densities and their infection rates overall decreased with aridity, from four
      species, an apparent density of 53.1 flies/trap/day and an infection rate of
      13.7% to an absence at the northern edge of the transect, where the density and
      diversity of other biting flies were on the contrary highest (p<0.001).
      CONCLUSIONS/SIGNIFICANCE: The climatic pressure clearly had a negative impact on
      tsetse abundance and AAT risk. However, the persistency of tsetse habitats along
      the Mouhoun river loop maintains a high risk of cyclical transmission of T.
      vivax. Moreover, an "epidemic mechanical livestock trypanosomosis" cycle is
      likely to occur in the northern site, where trypanosomes are brought in by cattle
      transhuming from the tsetse infested area and are locally transmitted by
      mechanical vectors. In Burkina Faso, the impact of tsetse thus extends to a
      buffer area around their distribution belt, corresponding to the herd
      transhumance radius.

PMID- 23166767
TI  - Evolution of body elongation in gymnophthalmid lizards: relationships with
      climate.
AB  - The evolution of elongated body shapes in vertebrates has intrigued biologists
      for decades and is particularly recurrent among squamates. Several aspects might
      explain how the environment influences the evolution of body elongation, but
      climate needs to be incorporated in this scenario to evaluate how it contributes
      to morphological evolution. Climatic parameters include temperature and
      precipitation, two variables that likely influence environmental characteristics,
      including soil texture and substrate coverage, which may define the selective
      pressures acting during the evolution of morphology. Due to development of
      geographic information system (GIS) techniques, these variables can now be
      included in evolutionary biology studies and were used in the present study to
      test for associations between variation in body shape and climate in the tropical
      lizard family Gymnophthalmidae. We first investigated how the morphological
      traits that define body shape are correlated in these lizards and then tested for
      associations between a descriptor of body elongation and climate. Our analyses
      revealed that the evolution of body elongation in Gymnophthalmidae involved
      concomitant changes in different morphological traits: trunk elongation was
      coupled with limb shortening and a reduction in body diameter, and the gradual
      variation along this axis was illustrated by less-elongated morphologies
      exhibiting shorter trunks and longer limbs. The variation identified in
      Gymnophthalmidae body shape was associated with climate, with the species from
      more arid environments usually being more elongated. Aridity is associated with
      high temperatures and low precipitation, which affect additional environmental
      features, including the habitat structure. This feature may influence the
      evolution of body shape because contrasting environments likely impose distinct
      demands for organismal performance in several activities, such as locomotion and
      thermoregulation. The present study establishes a connection between morphology
      and a broader natural component, climate, and introduces new questions about the
      spatial distribution of morphological variation among squamates.

PMID- 23166768
TI  - Scale-free brain-wave music from simultaneously EEG and fMRI recordings.
AB  - In the past years, a few methods have been developed to translate human EEG to
      music. In 2009, PloS One 4 e5915, we developed a method to generate scale-free
      brainwave music where the amplitude of EEG was translated to music pitch
      according to the power law followed by both of them, the period of an EEG
      waveform is translated directly to the duration of a note, and the logarithm of
      the average power change of EEG is translated to music intensity according to the
      Fechner's law. In this work, we proposed to adopt simultaneously-recorded fMRI
      signal to control the intensity of the EEG music, thus an EEG-fMRI music is
      generated by combining two different and simultaneous brain signals. And most
      importantly, this approach further realized power law for music intensity as fMRI
      signal follows it. Thus the EEG-fMRI music makes a step ahead in reflecting the
      physiological process of the scale-free brain.

PMID- 23166766
TI  - Molecular evolution and structural features of IRAK family members.
AB  - The interleukin-1 receptor-associated kinase (IRAK) family comprises critical
      signaling mediators of the TLR/IL-1R signaling pathways. IRAKs are Ser/Thr
      kinases. There are 4 members in the vertebrate genome (IRAK1, IRAK2, IRAKM, and
      IRAK4) and an IRAK homolog, Pelle, in insects. IRAK family members are highly
      conserved in vertebrates, but the evolutionary relationship between IRAKs in
      vertebrates and insects is not clear. To investigate the evolutionary history and
      functional divergence of IRAK members, we performed extensive bioinformatics
      analysis. The phylogenetic relationship between IRAK sequences suggests that gene
      duplication events occurred in the evolutionary lineage, leading to early
      vertebrates. A comparative phylogenetic analysis with insect homologs of IRAKs
      suggests that the Tube protein is a homolog of IRAK4, unlike the anticipated
      protein, Pelle. Furthermore, the analysis supports that an IRAK4-like kinase is
      an ancestral protein in the metazoan lineage of the IRAK family. Through
      functional analysis, several potentially diverged sites were identified in the
      common death domain and kinase domain. These sites have been constrained during
      evolution by strong purifying selection, suggesting their functional importance
      within IRAKs. In summary, our study highlighted the molecular evolution of the
      IRAK family, predicted the amino acids that contributed to functional divergence,
      and identified structural variations among the IRAK paralogs that may provide a
      starting point for further experimental investigations.

PMID- 23166769
TI  - Mental health literacy of depression: gender differences and attitudinal
      antecedents in a representative British sample.
AB  - BACKGROUND: Poor mental health literacy and negative attitudes toward individuals
      with mental health disorders may impede optimal help-seeking for symptoms of
      mental ill-health. The present study examined the ability to recognize cases of
      depression as a function of respondent and target gender, as well as individual
      psychological differences in attitudes toward persons with depression. METHODS:
      In a representative British general population survey, the ability to correctly
      recognize vignettes of depression was assessed among 1,218 adults. Respondents
      also rated the vignettes along a number of attitudinal dimensions and completed
      measures of attitudes toward seeking psychological help, psychiatric skepticism,
      and anti-scientific attitudes. RESULTS: There were significant differences in the
      ability to correctly identify cases of depression as a function of respondent and
      target gender. Respondents were more likely to indicate that a male vignette did
      not suffer from a mental health disorder compared to a female vignette, and women
      were more likely than men to indicate that the male vignette suffered from a
      mental health disorder. Attitudes toward persons with depression were associated
      with attitudes toward seeking psychological help, psychiatric skepticism, and
      anti-scientific attitudes. CONCLUSION: Initiatives that consider the impact of
      gender stereotypes as well as individual differences may enhance mental health
      literacy, which in turn is associated with improved help-seeking behaviors for
      symptoms of mental ill-health.

PMID- 23166770
TI  - Association of symptoms of attention-deficit/hyperactivity disorder with physical
      activity, media time, and food intake in children and adolescents.
AB  - INTRODUCTION: The aim of the study was to assess the association between
      attention deficit/hyperactivity disorder (ADHD) symptoms and potentially
      obesogenic behaviors. METHODS: Data of 11,676 German children and adolescents (6
      17 years) were analyzed. Television/video exposure, physical activity, food
      frequency and portion size were assessed using questionnaires. A dietary quality
      index, energy density and volumes of consumed food, and total energy intake were
      calculated. The parent-rated hyperactivity/inattention subscale of the Strengths
      and Difficulties Questionnaire (SDQ-HI) was used as a continuous measure of ADHD
      symptoms. Associations were analyzed with general linear models adjusting for
      sex, age, socioeconomic status, migrant status, parental BMI, and parental
      smoking. RESULTS: SDQ-HI scores correlated positively with physical activity,
      average energy density of food, volume of beverages, total energy intake, and
      television exposure and negatively with the nutritional quality score (HuSKY)
      even after adjustment for parental variables (BMI, smoking, socioeconomic status,
      migrant status), age, sex, as well as the other SDQ subscales. The adjusted
      association of the SDQ-HI scores with the nutritional quality score was stronger
      in girls and the associations with food volume, food energy, and total energy
      intake was significant only in girls. CONCLUSIONS: Poor nutritional quality, high
      energy intake and television exposure appear to be independently associated with
      ADHD symptoms. The relationship between food energy intake and ADHD symptoms was
      especially pronounced in girls and this may help to explain the reported
      association of ADHD symptoms with overweight in adolescent girls.

PMID- 23166771
TI  - Tract profiles of white matter properties: automating fiber-tract quantification.
AB  - Tractography based on diffusion weighted imaging (DWI) data is a method for
      identifying the major white matter fascicles (tracts) in the living human brain.
      The health of these tracts is an important factor underlying many cognitive and
      neurological disorders. In vivo, tissue properties may vary systematically along
      each tract for several reasons: different populations of axons enter and exit the
      tract, and disease can strike at local positions within the tract. Hence
      quantifying and understanding diffusion measures along each fiber tract (Tract
      Profile) may reveal new insights into white matter development, function, and
      disease that are not obvious from mean measures of that tract. We demonstrate
      several novel findings related to Tract Profiles in the brains of typically
      developing children and children at risk for white matter injury secondary to
      preterm birth. First, fractional anisotropy (FA) values vary substantially within
      a tract but the Tract FA Profile is consistent across subjects. Thus, Tract
      Profiles contain far more information than mean diffusion measures. Second,
      developmental changes in FA occur at specific positions within the Tract Profile,
      rather than along the entire tract. Third, Tract Profiles can be used to compare
      white matter properties of individual patients to standardized Tract Profiles of
      a healthy population to elucidate unique features of that patient's clinical
      condition. Fourth, Tract Profiles can be used to evaluate the association between
      white matter properties and behavioral outcomes. Specifically, in the preterm
      group reading ability is positively correlated with FA measured at specific
      locations on the left arcuate and left superior longitudinal fasciculus and the
      magnitude of the correlation varies significantly along the Tract Profiles. We
      introduce open source software for automated fiber-tract quantification (AFQ)
      that measures Tract Profiles of MRI parameters for 18 white matter tracts. With
      further validation, AFQ Tract Profiles have potential for informing clinical
      management and decision-making.

PMID- 23166772
TI  - Natural or artificial? Habitat-use by the bull shark, Carcharhinus leucas.
AB  - BACKGROUND: Despite accelerated global population declines due to targeted and
      illegal fishing pressure for many top-level shark species, the impacts of coastal
      habitat modification have been largely overlooked. We present the first direct
      comparison of the use of natural versus artificial habitats for the bull shark,
      Carcharhinus leucas, an IUCN 'Near-threatened' species--one of the few truly
      euryhaline sharks that utilises natural rivers and estuaries as nursery grounds
      before migrating offshore as adults. Understanding the value of alternate
      artificial coastal habitats to the lifecycle of the bull shark is crucial for
      determining the impact of coastal development on this threatened but potentially
      dangerous species. METHODOLOGY/FINDINGS: We used longline surveys and long-term
      passive acoustic tracking of neonate and juvenile bull sharks to determine the
      ontogenetic value of natural and artificial habitats to bull sharks associated
      with the Nerang River and adjoining canals on the Gold Coast, Australia. Long
      term movements of tagged sharks suggested a preference for the natural river over
      artificial habitat (canals). Neonates and juveniles spent the majority of their
      time in the upper tidal reaches of the Nerang River and undertook excursions into
      adjoining canals. Larger bull sharks ranged further and frequented the canals
      closer to the river mouth. CONCLUSIONS/SIGNIFICANCE: Our work suggests with
      increased destruction of natural habitats, artificial coastal habitat may become
      increasingly important to large juvenile bull sharks with associated risk of
      attack on humans. In this system, neonate and juvenile bull sharks utilised the
      natural and artificial habitats, but the latter was not the preferred habitat of
      neonates. The upper reaches of tidal rivers, often under significant modification
      pressure, serve as nursery sites for neonates. Analogous studies are needed in
      similar systems elsewhere to assess the spatial and temporal generality of this
      research.

PMID- 23166773
TI  - Regulation of CD4+ and CD8+ effector responses by Sprouty-1.
AB  - TCR-induced NF-AT activation leads to the expression of both activating and
      inhibitory proteins. Previously, we had identified Egr-2 and Egr-3 as NF-AT
      induced transcription factors which promote the inhibition of T cell activation.
      In this report we identify Sprouty1 as a downstream target of Egr-3. CD4+ T cells
      lacking Spry1 demonstrate enhanced proliferation and cytokine production.
      Likewise, Spry1(Flox/Flox) Lck Cre CD8+ T cells display increased cytolytic
      activity. Mechanistically, Spry1 acts at the level of PLC-gamma promoting the
      inhibition of both Ca++ induced NF-AT activation and MAP-kinase induced AP-1
      activation while sparing NF-kappaB signaling. In vivo, mice in which Spry1 is
      selectively deleted in T cells demonstrate enhanced responses to a tumor vaccine
      and subsequently reject tumors more robustly than Wt mice. These findings suggest
      that targeting Spry1 might prove to be a novel means of enhancing tumor
      immunotherapy.

PMID- 23166774
TI  - Giant robber crabs monitored from space: GPS-based telemetric studies on
      Christmas Island (Indian Ocean).
AB  - We investigated the navigational capabilities of the world's largest land-living
      arthropod, the giant robber crab Birgus latro (Anomura, Coenobitidae); this crab
      reaches 4 kg in weight and can reach an age of up to 60 years. Populations are
      distributed over small Indo-Pacific islands of the tropics, including Christmas
      Island (Indian Ocean). Although this species has served as a crustacean model to
      explore anatomical, physiological, and ecological aspects of terrestrial
      adaptations, few behavioral analyses of it exist. We used a GPS-based telemetric
      system to analyze movements of freely roaming robber crabs, the first large-scale
      study of any arthropod using GPS technology to monitor behavior. Although female
      robber crabs are known to migrate to the coast for breeding, no such observations
      have been recorded for male animals. In total, we equipped 55 male robber crabs
      with GPS tags, successfully recording more than 1,500 crab days of activity, and
      followed some individual animals for as long as three months. Besides site
      fidelity with short-distance excursions, our data reveal long-distance movements
      (several kilometers) between the coast and the inland rainforest. These movements
      are likely related to mating, saltwater drinking and foraging. The tracking
      patterns indicate that crabs form route memories. Furthermore, translocation
      experiments show that robber crabs are capable of homing over large distances. We
      discuss if the search behavior induced in these experiments suggests path
      integration as another important navigation strategy.

PMID- 23166775
TI  - Identification of microRNAs from Eugenia uniflora by high-throughput sequencing
      and bioinformatics analysis.
AB  - BACKGROUND: microRNAs or miRNAs are small non-coding regulatory RNAs that play
      important functions in the regulation of gene expression at the post
      transcriptional level by targeting mRNAs for degradation or inhibiting protein
      translation. Eugenia uniflora is a plant native to tropical America with
      pharmacological and ecological importance, and there have been no previous
      studies concerning its gene expression and regulation. To date, no miRNAs have
      been reported in Myrtaceae species. RESULTS: Small RNA and RNA-seq libraries were
      constructed to identify miRNAs and pre-miRNAs in Eugenia uniflora. Solexa
      technology was used to perform high throughput sequencing of the library, and the
      data obtained were analyzed using bioinformatics tools. From 14,489,131 small RNA
      clean reads, we obtained 1,852,722 mature miRNA sequences representing 45
      conserved families that have been identified in other plant species. Further
      analysis using contigs assembled from RNA-seq allowed the prediction of secondary
      structures of 25 known and 17 novel pre-miRNAs. The expression of twenty-seven
      identified miRNAs was also validated using RT-PCR assays. Potential targets were
      predicted for the most abundant mature miRNAs in the identified pre-miRNAs based
      on sequence homology. CONCLUSIONS: This study is the first large scale
      identification of miRNAs and their potential targets from a species of the
      Myrtaceae family without genomic sequence resources. Our study provides more
      information about the evolutionary conservation of the regulatory network of
      miRNAs in plants and highlights species-specific miRNAs.

PMID- 23166776
TI  - Clinical, ethical and financial implications of incidental imaging findings:
      experience from a phase I trial in healthy elderly volunteers.
AB  - BACKGROUND: The detection of incidental findings (IF) in magnetic resonance
      imaging (MRI) studies is common and increases as a function of age. Responsible
      handling of IF is required, with implications for the conduct of research and the
      provision of good clinical care. AIM: To investigate the prevalence and clinical
      significance of IF in a prospective cohort of healthy elderly volunteers who
      underwent MRI of the torso as a baseline investigation for a phase I trial. We
      assessed the follow-up pathway with consequent cost implications and impact on
      trial outcomes. METHODS: A total of 29 elderly healthy volunteers (mean age 67,
      range 61-77, 59% female) were eligible at screening and underwent MRI for
      assessment of visceral and subcutaneous fat. RESULTS: IF were detected in 19
      subjects (66%). Suspected IF of high and low clinical significance were found in
      14% and 52% of participants, respectively. Follow up of IF was conducted in 18
      individuals, confirming abnormalities in 13 subjects, 3 of whom were recommended
      for deferred clinical re-evaluation. The remaining 5 subjects had false positive
      IF based on second line imaging tests. Costs of follow-up medical care were
      considerable. CONCLUSION: MRI abnormalities are common in elderly individuals, as
      a result of age and non-diagnostic quality of research scans. In the presence of
      IF in the context of clinical trials, immediate referrals and follow up
      assessments may be required to rule out suspected pathology prior to exposing
      trial participants to investigational medicine products (IMP). Unanticipated
      costs, ethical implication and the possible impact of IF on trial outcomes need
      to be taken into account when designing and conducting trials with an IMP.

PMID- 23166777
TI  - Understanding plant community responses to combinations of biotic and abiotic
      factors in different phases of the plant growth cycle.
AB  - Understanding plant community responses to combinations of biotic and abiotic
      factors is critical for predicting ecosystem response to environmental change.
      However, studies of plant community regulation have seldom considered how
      responses to such factors vary with the different phases of the plant growth
      cycle. To address this deficit we studied an aquatic plant community in an
      ecosystem subject to gradients in mute swan (Cygnus olor) herbivory, riparian
      shading, water temperature and distance downstream of the river source. We
      quantified abundance, species richness, evenness, flowering and dominance in
      relation to biotic and abiotic factors during the growth-, peak-, and recession
      phases of the plant growth cycle. We show that the relative importance of biotic
      and abiotic factors varied between plant community properties and between
      different phases of the plant growth cycle. Herbivory became more important
      during the later phases of peak abundance and recession due to an influx of swans
      from adjacent pasture fields. Shading by riparian vegetation also had a greater
      depressing effect on biomass in later seasons, probably due to increased leaf
      abundance reducing light intensity reaching the aquatic plants. The effect of
      temperature on community diversity varied between upstream and downstream sites
      by altering the relative competitiveness of species at these sites. These results
      highlight the importance of seasonal patterns in the regulation of plant
      community structure and function by multiple factors.

PMID- 23166778
TI  - Retinal neurodegeneration in Wilson's disease revealed by spectral domain optical
      coherence tomography.
AB  - BACKGROUND/OBJECTIVE: In addition to cirrhosis of the liver, Wilson's disease
      leads to copper accumulation and widespread degeneration of the nervous system.
      Delayed visual evoked potentials (VEPs) suggest changes to the visual system and
      potential structural changes of the retina. METHODS: We used the latest
      generation of spectral domain optical coherence tomography to assess the retinal
      morphology of 42 patients with Wilson's disease and 76 age- and sex-matched
      controls. We measured peripapillary retinal nerve fiber layer (RNFL) thickness
      and total macular thickness and manually segmented all retinal layers in foveal
      scans of 42 patients with Wilson's disease and 76 age- and sex-matched controls.
      The results were compared with VEPs and clinical parameters. RESULTS: The mean
      thickness of the RNFL, paramacular region, retinal ganglion cell/inner plexiform
      layer and inner nuclear layer was reduced in Wilson's disease. VEPs were altered
      with delayed N75 and P100 latencies, but the N140 latency and amplitude was
      unchanged. An analysis of the laboratory parameters indicated that the serum
      concentrations of copper and caeruloplasmin positively correlated with the
      thickness of the outer plexiform layer and with N75 and P100 VEP latencies.
      CONCLUSION: Neuronal degeneration in Wilson's disease involves the retina and
      changes can be quantified by optical coherence tomography. While the VEPs and the
      thickness of the outer plexiform layer appear to reflect the current copper
      metabolism, the thicknesses of the RNFL, ganglion cell/inner plexiform layer,
      inner nuclear layer and the total paramacular thickness may be the best
      indicators of chronic neuronal degeneration.

PMID- 23166779
TI  - Whole number, distribution and co-expression of brn3 transcription factors in
      retinal ganglion cells of adult albino and pigmented rats.
AB  - The three members of the Pou4f family of transcription factors: Pou4f1, Pou4f2,
      Pou4f3 (Brn3a, Brn3b and Brn3c, respectively) play, during development, essential
      roles in the differentiation and survival of sensory neurons. The purpose of this
      work is to study the expression of the three Brn3 factors in the albino and
      pigmented adult rat. Animals were divided into these groups: i) untouched; ii)
      fluorogold (FG) tracing from both superior colliculli; iii) FG-tracing from one
      superior colliculus; iv) intraorbital optic nerve transection or crush. All
      retinas were dissected as flat-mounts and subjected to single, double or triple
      immunohistofluorescence The total number of FG-traced, Brn3a, Brn3b, Brn3c or
      Brn3 expressing RGCs was automatically quantified and their spatial distribution
      assessed using specific routines. Brn3 factors were studied in the general RGC
      population, and in the intrinsically photosensitive (ip-RGCs) and ipsilateral RGC
      sub-populations. Our results show that: i) 70% of RGCs co- express two or three
      Brn3s and the remaining 30% express only Brn3a (26%) or Brn3b; ii) the most
      abundant Brn3 member is Brn3a followed by Brn3b and finally Brn3c; iii) Brn3 a-,
      b- or c- expressing RGCs are similarly distributed in the retina; iv) The vast
      majority of ip-RGCs do not express Brn3; v) The main difference between both rat
      strains was found in the population of ipsilateral-RGCs, which accounts for 4.2%
      and 2.5% of the total RGC population in the pigmented and albino strain,
      respectively. However, more ipsilateral-RGCs express Brn3 factors in the albino
      than in the pigmented rat; vi) RGCs that express only Brn3b and RGCs that co
      express the three Brn3 members have the biggest nuclei; vii) After axonal injury
      the level of Brn3a expression in the surviving RGCs decreases compared to control
      retinas. Finally, this work strengthens the validity of Brn3a as a marker to
      identify and quantify rat RGCs.

PMID- 23166780
TI  - IFN regulatory factor 8 is a key constitutive determinant of the morphological
      and molecular properties of microglia in the CNS.
AB  - IFN regulatory factor (IRF) 8 is a transcription factor that has a key role in
      the cellular response to IFN-gamma and is pivotal in myeloid cell
      differentiation. Whether IRF8 plays a role in the development and function of
      microglia, the tissue-resident myeloid cells of the brain, is unknown. Here, we
      show IRF8 is a constitutively produced nuclear factor in microglia, which
      suggested that IRF8 might also be a key homeostatic transcriptional determinant
      of the microglial cell phenotype. In support of this, in mice with a targeted
      disruption of the IRF8 gene, microglia were increased in number and showed gross
      alterations in morphology and surface area. In situ analysis of some key myeloid
      markers revealed that IRF8-deficient microglia had significantly reduced levels
      of Iba1, but increased levels of CD206 (mannose receptor) and F4/80 as well as
      increased tomato lectin binding. Analysis of microglia ex vivo revealed IRF8
      deficient microglia had significantly increased levels of CD45, CD11b and F4/80,
      but significantly decreased levels of the chemokine receptors CCR2, CCR5 and
      CX3CR1. The known involvement of some of these molecular markers in membrane
      dynamics and phagocytosis led us to examine the phagocytic capacity of cultured
      IRF8-deficient microglia, however, this was found to be similar to wild type
      microglia. We conclude IRF8 is a constitutively produced nuclear factor in
      resident microglia of the CNS being a crucial transcriptional determinant of the
      phenotype of these cells in the healthy brain.

PMID- 23166781
TI  - Hypoxia increases mouse satellite cell clone proliferation maintaining both in
      vitro and in vivo heterogeneity and myogenic potential.
AB  - Satellite cells (SCs) are essential for postnatal muscle growth and regeneration,
      however, their expansion potential in vitro is limited. Recently, hypoxia has
      been used to enhance proliferative abilities in vitro of various primary
      cultures. Here, by isolating SCs from single mouse hindlimb skeletal myofibers,
      we were able to distinguish two subpopulations of clonally cultured SCs (Low
      Proliferative Clones--LPC--and High Proliferative Clones--HPC), which, as shown
      in rat skeletal muscle, were present at a fixed proportion. In addition,
      culturing LPC and HPC at a low level of oxygen we observed a two fold increased
      proliferation both for LPC and HPC. LPC showed higher myogenic regulatory factor
      (MRF) expression than HPC, particularly under the hypoxic condition. Notably, a
      different myogenic potential between LPC and HPC was retained in vivo: green
      fluorescent protein (GFP)+LPC transplantation in cardiotoxin-injured Tibialis
      Anterior led to a higher number of new GFP+muscle fibers per transplanted cell
      than GFP+HPC. Interestingly, the in vivo myogenic potential of a single cell from
      an LPC is similar if cultured both in normoxia and hypoxia. Therefore, starting
      from a single satellite cell, hypoxia allows a larger expansion of LPC than
      normal O(2) conditions, obtaining a consistent amount of cells for
      transplantation, but maintaining their myogenic regeneration potential.

PMID- 23166782
TI  - Metformin reduces hepatic expression of SIRT3, the mitochondrial deacetylase
      controlling energy metabolism.
AB  - Metformin inhibits ATP production in mitochondria and this may be involved in the
      anti-hyperglycemic effects of the drug. Sirtuin 3 (SIRT3) is a mitochondrial
      protein deacetylase that regulates the function of the electron transport chain
      and maintains basal ATP yield. We hypothesized that metformin treatment could
      diminish mitochondrial ATP production through downregulation of SIRT3 expression.
      Glucagon and cAMP induced SIRT3 mRNA in mouse primary hepatocytes. Metformin
      prevented SIRT3 induction by glucagon. Moreover, metformin downregulated
      constitutive expression of SIRT3 in primary hepatocytes and in the liver in vivo.
      Estrogen related receptor alpha (ERRalpha) mediates regulation of Sirt3 gene by
      peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC
      1alpha). ERRalpha mRNA expression was regulated in a similar manner as SIRT3 mRNA
      by glucagon, cAMP and metformin. However, a higher metformin concentration was
      required for downregulation of ERRalpha than SIRT3. ERRalpha siRNA attenuated PGC
      1alpha mediated induction of SIRT3, but did not affect constitutive expression.
      Overexpression of the constitutively active form of AMP-activated protein kinase
      (AMPK) induced SIRT3 mRNA, indicating that the SIRT3 downregulation by metformin
      is not mediated by AMPK. Metformin reduced the hepatocyte ATP level. This effect
      was partially counteracted by SIRT3 overexpression. Furthermore, metformin
      decreased mitochondrial SIRT3 protein levels and this was associated with
      enhanced acetylation of several mitochondrial proteins. However, metformin
      increased mitochondrial mass in hepatocytes. Altogether, our results indicate
      that metformin attenuates mitochondrial expression of SIRT3 and suggest that this
      mechanism is involved in regulation of energy metabolism by metformin in the
      liver and may contribute to the therapeutic action of metformin.

PMID- 23166783
TI  - An attempt at a molecular prediction of metastasis in patients with primary
      cutaneous melanoma.
AB  - BACKGROUND: Current prognostic clinical and morphological parameters are
      insufficient to accurately predict metastasis in individual melanoma patients.
      Several studies have described gene expression signatures to predict survival or
      metastasis of primary melanoma patients, however the reproducibility among these
      studies is disappointingly low. METHODOLOGY/PRINCIPAL FINDINGS: We followed
      extended REMARK/Gould Rothberg criteria to identify gene sets predictive for
      metastasis in patients with primary cutaneous melanoma. For class comparison,
      gene expression data from 116 patients with clinical stage I/II (no metastasis)
      and 72 with III/IV primary melanoma (with metastasis) at time of first diagnosis
      were used. Significance analysis of microarrays identified the top 50
      differentially expressed genes. In an independent data set from a second cohort
      of 28 primary melanoma patients, these genes were analyzed by multivariate Cox
      regression analysis and leave-one-out cross validation for association with
      development of metastatic disease. In a multivariate Cox regression analysis,
      expression of the genes Ena/vasodilator-stimulated phosphoprotein-like (EVL) and
      CD24 antigen gave the best predictive value (p = 0.001; p = 0.017, respectively).
      A multivariate Cox proportional hazards model revealed these genes as a potential
      independent predictor, which may possibly add (both p = 0.01) to the predictive
      value of the most important morphological indicator, Breslow depth.
      CONCLUSION/SIGNIFICANCE: Combination of molecular with morphological information
      may potentially enable an improved prediction of metastasis in primary melanoma
      patients. A strength of the gene expression set is the small number of genes,
      which should allow easy reevaluation in independent data sets and adequately
      designed clinical trials.

PMID- 23166784
TI  - Effects of cold pressor stress on the human startle response.
AB  - Both emotion and attention are known to influence the startle response. Stress
      influences emotion and attention, but the impact of stress on the human startle
      response remains unclear. We used an established physiological stressor, the Cold
      Pressor Test (CPT), to induce stress in a non-clinical human sample (24 student
      participants) in a within-subjects design. Autonomic (heart rate and skin
      conductance) and somatic (eye blink) responses to acoustic startle probes were
      measured during a pre-stress baseline, during a three minutes stress
      intervention, and during the subsequent recovery period. Startle skin conductance
      and heart rate responses were facilitated during stress. Compared to baseline,
      startle eye blink responses were not affected during the intervention but were
      diminished afterwards. These data describe a new and unique startle response
      pattern during stress: facilitation of autonomic stress responses but no such
      facilitation of somatic startle eye blink responses. The absence of an effect of
      stress on startle eye blink responsiveness may illustrate the importance of
      guaranteeing uninterrupted visual input during periods of stress.

PMID- 23166785
TI  - Contact investigation in households of patients with tuberculosis in Hanoi,
      Vietnam: a prospective cohort study.
AB  - SETTING: Existing tuberculosis control strategies in Vietnam are based on
      symptomatic patients attending health services for investigation. This approach
      has not resulted in substantial reductions in the prevalence of tuberculosis
      disease, despite the National Tuberculosis Program achieving high treatment
      completion rates. Alternative approaches are being considered. OBJECTIVE: To
      determine the feasibility and yield of contact investigation in households of
      patients with smear positive pulmonary tuberculosis among household members of
      tuberculosis patients in Hanoi, Vietnam. METHODS: Household contacts of patients
      with smear positive pulmonary tuberculosis were recruited at four urban and rural
      District Tuberculosis Units in Hanoi. Clinical and radiological screening was
      conducted at baseline, six months and 12 months. Sputum microscopy and culture
      was performed in contacts suspected of having tuberculosis. MIRU-VNTR molecular
      testing was used to compare the strains of patients and their contacts with
      disease. RESULTS: Among 545 household contacts of 212 patients, four were
      diagnosed with tuberculosis at baseline (prevalence 734 cases per 100,000
      persons, 95% CI 17-1451) and one was diagnosed with tuberculosis during the
      subsequent 12 months after initial screening (incidence 180 cases per 100,000
      person-years, 95% CI 44-131). Two of these cases were culture positive for M.
      tuberculosis and both had identical or near-identical MIRU-VNTR strain types.
      CONCLUSION: Household contacts of patients with potentially infectious forms of
      tuberculosis have a high prevalence of disease. Household contact investigation
      is feasible in Vietnam. Further research is required to investigate its
      effectiveness.

PMID- 23166786
TI  - Interferon-beta induces hepatocyte growth factor in monocytes of multiple
      sclerosis patients.
AB  - Interferon-beta is a first-line therapy used to prevent relapses in relapsing
      remitting multiple sclerosis. The clinical benefit of interferon-beta in
      relapsing-remitting multiple sclerosis is attributed to its immunomodulatory
      effects on inflammatory mediators and T cell reactivity. Here, we evaluated the
      production of hepatocyte growth factor, a neuroprotective and neuroinflammation
      suppressive mediator, by peripheral blood mononuclear cells collected from
      interferon-beta--treated relapsing-remitting multiple sclerosis patients,
      relapsing remitting multiple sclerosis patients not treated with interferon-beta,
      and healthy volunteers. Using intracellular flow cytometry analysis, increased
      production of hepatocyte growth factor was observed in circulating CD14(+)
      monocytes from patients undergoing long-term treatment with interferon-beta
      versus untreated patients. Complementary in vitro studies confirmed that
      treatment with interferon-beta induced rapid and transient transcription of the
      hepatocyte growth factor gene in CD14(+) monocytes and that intracellular and
      secreted monocytic hepatocyte growth factor protein levels were markedly
      stimulated by interferon-beta treatment. Additional exploration revealed that
      "pro-inflammatory" (CD14(+)CD16(+)) monocytes produced similar levels of
      hepatocyte growth factor in response to interferon-beta as "classical"
      (CD14(+)CD16(-)) monocytes, and that CD14(+) monocytes but not CD4(+) T cells
      express the hepatocyte growth factor receptor c-Met. Our findings suggest that
      interferon-beta may mediate some of its therapeutic effects in relapsing
      remitting multiple sclerosis through the induction of hepatocyte growth factor by
      blood monocytes by coupling immune regulation and neuroprotection.

PMID- 23166787
TI  - Physical organization of DNA by multiple non-specific DNA-binding modes of
      integration host factor (IHF).
AB  - The integration host factor (IHF) is an abundant nucleoid-associated protein and
      an essential co-factor for phage lambda site-specific recombination and gene
      regulation in E. coli. Introduction of a sharp DNA kink at specific cognate sites
      is critical for these functions. Interestingly, the intracellular concentration
      of IHF is much higher than the concentration needed for site-specific
      interactions, suggesting that non-specific binding of IHF to DNA plays a role in
      the physical organization of bacterial chromatin. However, it is unclear how non
      specific DNA association contributes to DNA organization. By using a combination
      of single DNA manipulation and atomic force microscopy imaging methods, we show
      here that distinct modes of non-specific DNA binding of IHF result in complex
      global DNA conformations. Changes in KCl and IHF concentrations, as well as
      tension applied to DNA, dramatically influence the degree of DNA-bending. In
      addition, IHF can crosslink DNA into a highly compact DNA meshwork that is
      observed in the presence of magnesium at low concentration of monovalent ions and
      high IHF-DNA stoichiometries. Our findings provide important insights into how
      IHF contributes to bacterial chromatin organization, gene regulation, and biofilm
      formation.

PMID- 23166788
TI  - Healthier fundraising in U. S. elementary schools: associations between policies
      at the state, district, and school levels.
AB  - OBJECTIVES: We examined whether state laws and district policies pertaining to
      nutritional restrictions on school fundraisers were associated with school
      policies as reported by administrators in a nationally-representative sample of
      United States public elementary schools. METHODS: We gathered data on school
      level fundraising policies via a mail-back survey during the 2009-10 and 2010-11
      school years. Surveys were received from 1,278 public elementary schools
      (response rate = 60.9%). Data were also gathered on corresponding school district
      policies and state laws. After removing cases with missing data, the sample size
      for analysis was 1,215 schools. RESULTS: After controlling for school
      characteristics, school policies were consistently associated with state laws and
      district policies, both those pertaining to fundraising generally, as well as
      specific restrictions on the sale of candy and soda in fundraisers (all Odds
      Ratios >2.0 and Ps<.05). However, even where district policies and state laws
      required fundraising restrictions, school policies were not uniformly present;
      school policies were also in place at only 55.8% of these schools, but were more
      common at schools in the West (77.1%) and at majority-Latino schools (71.4%),
      indicating uneven school-level implementation of district policy and state law.
      CONCLUSIONS: District policies and state laws were associated with a higher
      prevalence of elementary school-level fundraising policies, but many schools that
      were subject to district policies and state laws did not have school-level
      restrictions in place, suggesting the need for further attention to factors
      hindering policy implementation in schools.

PMID- 23166789
TI  - A simplified method for the efficient refolding and purification of recombinant
      human GM-CSF.
AB  - Human granulocyte macrophage colony-stimulating factor (hGM-CSF) is a
      haematopoietic growth factor and proinflammatory cytokine. Recombinant hGM-CSF is
      important not only as a research tool but also as a biotherapeutic. However, rhGM
      CSF expressed in E. coli is known to form inclusion bodies of misfolded,
      aggregated protein. Refolding and subsequent purification of rhGM-CSF from
      inclusion bodies is difficult with low yields of bioactive protein being
      produced. Here we describe a method for the isolation, refolding and purification
      of bioactive rhGM-CSF from inclusion bodies. The method is straightforward, not
      requiring extensive experience in protein refolding nor purification and using
      standard laboratory equipment.

PMID- 23166790
TI  - A novel interplay between Rap1 and PKA regulates induction of angiogenesis in
      prostate cancer.
AB  - Angiogenesis inhibition is an important therapeutic strategy for advanced stage
      prostate cancer. Previous work from our laboratory showed that sustained
      stimulation of Rap1 by 8-pCPT-2'-O-Me-cAMP (8CPT) via activation of Epac, a Rap1
      GEF, or by expression of a constitutively active Rap1 mutant (cRap1) suppresses
      endothelial cell chemotaxis and subsequent angiogenesis. When we tested this
      model in the context of a prostate tumor xenograft, we found that 8CPT had no
      significant effect on prostate tumor growth alone. However, in cells harboring
      cRap1, 8CPT dramatically inhibited not only prostate tumor growth but also VEGF
      expression and angiogenesis within the tumor microenvironment. Subsequent
      analysis of the mechanism revealed that, in prostate tumor epithelial cells, 8CPT
      acted via stimulation of PKA rather than Epac/Rap1. PKA antagonizes Rap1 and
      hypoxic induction of 1alpha protein expression, VEGF production and, ultimately,
      angiogenesis. Together these findings provide evidence for a novel interplay
      between Rap1, Epac, and PKA that regulates tumor-stromal induction of
      angiogenesis.

PMID- 23166791
TI  - Searching the clinical fitness landscape.
AB  - Widespread unexplained variations in clinical practices and patient outcomes
      suggest major opportunities for improving the quality and safety of medical care.
      However, there is little consensus regarding how to best identify and disseminate
      healthcare improvements and a dearth of theory to guide the debate. Many consider
      multicenter randomized controlled trials to be the gold standard of evidence
      based medicine, although results are often inconclusive or may not be generally
      applicable due to differences in the contexts within which care is provided.
      Increasingly, others advocate the use "quality improvement collaboratives", in
      which multi-institutional teams share information to identify potentially better
      practices that are subsequently evaluated in the local contexts of specific
      institutions, but there is concern that such collaborative learning approaches
      lack the statistical rigor of randomized trials. Using an agent-based model, we
      show how and why a collaborative learning approach almost invariably leads to
      greater improvements in expected patient outcomes than more traditional
      approaches in searching simulated clinical fitness landscapes. This is due to a
      combination of greater statistical power and more context-dependent evaluation of
      treatments, especially in complex terrains where some combinations of practices
      may interact in affecting outcomes. The results of our simulations are consistent
      with observed limitations of randomized controlled trials and provide important
      insights into probable reasons for effectiveness of quality improvement
      collaboratives in the complex socio-technical environments of healthcare
      institutions. Our approach illustrates how modeling the evolution of medical
      practice as search on a clinical fitness landscape can aid in identifying and
      understanding strategies for improving the quality and safety of medical care.

PMID- 23166792
TI  - Reconstruction of Danio rerio metabolic model accounting for subcellular
      compartmentalisation.
AB  - Plant and microbial metabolic engineering is commonly used in the production of
      functional foods and quality trait improvement. Computational model-based
      approaches have been used in this important endeavour. However, to date, fish
      metabolic models have only been scarcely and partially developed, in marked
      contrast to their prominent success in metabolic engineering. In this study we
      present the reconstruction of fully compartmentalised models of the Danio rerio
      (zebrafish) on a global scale. This reconstruction involves extraction of known
      biochemical reactions in D. rerio for both primary and secondary metabolism and
      the implementation of methods for determining subcellular localisation and
      assignment of enzymes. The reconstructed model (ZebraGEM) is amenable for
      constraint-based modelling analysis, and accounts for 4,988 genes coding for
      2,406 gene-associated reactions and only 418 non-gene-associated reactions. A set
      of computational validations (i.e., simulations of known metabolic
      functionalities and experimental data) strongly testifies to the predictive
      ability of the model. Overall, the reconstructed model is expected to lay down
      the foundations for computational-based rational design of fish metabolic
      engineering in aquaculture.

PMID- 23166793
TI  - Maturation and activity of sterol regulatory element binding protein 1 is
      inhibited by acyl-CoA binding domain containing 3.
AB  - Imbalance of lipid metabolism has been linked with pathogenesis of a variety of
      human pathological conditions such as diabetes, obesity, cancer and
      neurodegeneration. Sterol regulatory element binding proteins (SREBPs) are the
      master transcription factors controlling the homeostasis of fatty acids and
      cholesterol in the body. Transcription, expression, and activity of SREBPs are
      regulated by various nutritional, hormonal or stressful stimuli, yet the
      molecular and cellular mechanisms involved in these adaptative responses remains
      elusive. In the present study, we found that overexpressed acyl-CoA binding
      domain containing 3 (ACBD3), a Golgi-associated protein, dramatically inhibited
      SREBP1-sensitive promoter activity of fatty acid synthase (FASN). Moreover, lipid
      deprivation-stimulated SREBP1 maturation was significantly attenuated by ACBD3.
      With cell fractionation, gene knockdown and immunoprecipitation assays, it was
      showed that ACBD3 blocked intracellular maturation of SREBP1 probably through
      directly binding with the lipid regulator rather than disrupted SREBP1-SCAP
      Insig1 interaction. Further investigation revealed that acyl-CoA domain
      containing N-terminal sequence of ACBD3 contributed to its inhibitory effects on
      the production of nuclear SREBP1. In addition, mRNA and protein levels of FASN
      and de novo palmitate biosynthesis were remarkably reduced in cells overexpressed
      with ACBD3. These findings suggest that ACBD3 plays an essential role in
      maintaining lipid homeostasis via regulating SREBP1's processing pathway and thus
      impacting cellular lipogenesis.

PMID- 23166794
TI  - Cortical and spinal excitability during and after lengthening contractions of the
      human plantar flexor muscles performed with maximal voluntary effort.
AB  - This study was designed to investigate the sites of potential specific
      modulations in the neural control of lengthening and subsequent isometric maximal
      voluntary contractions (MVCs) versus purely isometric MVCs of the plantar flexor
      muscles, when there is enhanced torque during and following stretch. Ankle joint
      torque during maximum voluntary plantar flexion was measured by a dynamometer
      when subjects (n = 10) lay prone on a bench with the right ankle tightly strapped
      to a foot-plate. Neural control was analysed by comparing soleus motor responses
      to electrical nerve stimulation (M-wave, V-wave), electrical stimulation of the
      cervicomedullary junction (CMEP) and transcranial magnetic stimulation of the
      motor cortex (MEP). Enhanced torque of 17 +/- 8% and 9 +/- 8% was found during
      and 2.5-3 s after lengthening MVCs, respectively. Cortical and spinal
      responsiveness was similar to that in isometric conditions during the lengthening
      MVCs, as shown by unchanged MEPs, CMEPs and V-waves, suggesting that the major
      voluntary motor pathways are not subject to substantial inhibition. Following the
      lengthening MVCs, enhanced torque was accompanied by larger MEPs (p <= 0.05) and
      a trend to greater V-waves (p <= 0.1). In combination with stable CMEPs,
      increased MEPs suggest an increase in cortical excitability, and enlarged V-waves
      indicate greater motoneuronal output or increased stretch reflex excitability.
      The new results illustrate that neuromotor pathways are altered after lengthening
      MVCs suggesting that the underlying mechanisms of the enhanced torque are not
      purely mechanical in nature.

PMID- 23166795
TI  - Observational study of the association of first insulin type in uncontrolled type
      2 diabetes with macrovascular and microvascular disease.
AB  - AIMS: To compare the risk of vascular disease, HbA1c and weight change, between
      first prescribed insulins in people with type 2 diabetes. METHODS: People
      included in THIN United Kingdom primary care record database who began insulin
      (2000-2007) after poor control on oral glucose-lowering agents (OGLD) were
      grouped by the number of OGLDs in their treatment regimen immediately before
      starting insulin (n = 3,485). Within OGLD group, Cox regression compared
      macrovascular (all-cause mortality, myocardial infarction, acute coronary
      syndrome and stroke) and microvascular disease (peripheral neuropathy,
      nephropathy, and retinopathy) between insulin type (basal, pre-mix or Neutral
      Protamine Hagedorn, NPH) while ANCOVAs compared haemoglobin A(1c) (HbA(1c)) and
      weight change. RESULTS: Mean follow-up was 3.6 years. Rates of incident
      macrovascular events were similar when basal insulin was compared to pre-mix or
      NPH, adjusted hazard ratio versus basal: pre-mix 1.08 (95% CI 0.73, 1.59); NPH
      1.00 (0.63, 1.58) after two OGLDs, and pre-mix 0.97 (0.46, 2.02); NPH 0.77 (0.32,
      1.86) after three OGLDs. An increased risk of microvascular disease in NPH versus
      basal after 3 OGLDs, adjusted hazard ratio 1.87 (1.04, 3.36), was not seen after
      two agents or in comparisons of basal and pre-mix. At one year, after two OGLDs,
      weight increase was less with basal compared with pre-mix. After three OGLDs,
      mean HbA(1c) had reduced less in basal versus pre-mix or NPH at 6-8 and at 9-11
      months, and versus pre-mix at 12-14 months. CONCLUSION: We found no difference in
      the risk of macrovascular events between first insulins in the medium term when
      started during poor glycaemia control. The increased risk of microvascular events
      with NPH warrants further study. In certain groups, first use of basal insulin
      was associated with less gain in weight and decrease in HbA(1c) compared to other
      insulins.

PMID- 23166796
TI  - Determinants of antimicrobial resistance in Escherichia coli strains isolated
      from faeces and urine of women with recurrent urinary tract infections.
AB  - For women with recurrent urinary tract infections (rUTI), the contribution of
      antibiotic use versus patient-related factors in determining the presence of
      antimicrobial resistance in faecal and urinary Escherichia coli, obtained from
      the same patient population, has not been assessed yet. Within the context of the
      'Non-antibiotic prophylaxis for recurrent urinary tract infections' (NAPRUTI)
      study, the present study assessed determinants of antimicrobial resistance in E.
      coli isolated from urinary and faecal samples of women with rUTIs collected at
      baseline. Potential determinants of resistance were retrieved from self
      administered questionnaires. From 434 asymptomatic women, 433 urinary and 424
      faecal samples were obtained. E. coli was isolated from 146 (34%) urinary samples
      and from 336 (79%) faecal samples, and subsequently tested for antimicrobial
      susceptibility. Multivariable analysis showed trimethoprim/sulfamethoxazole (SXT)
      use three months prior to inclusion to be associated with urine E. coli
      resistance to amoxicillin (OR 3.6, 95% confidence interval: 1.3-9.9), amoxicillin
      clavulanic acid (OR 4.4, 1.5-13.3), trimethoprim (OR 3.9, 1.4-10.5) and SXT (OR
      3.2, 1.2-8.5), and with faecal E. coli resistance to trimethoprim (OR 2.0, 1.0
      3.7). The number of UTIs in the preceding year was correlated with urine E. coli
      resistance to amoxicillin-clavulanic acid (OR 1.11, 1.01-1.22), trimethoprim (OR
      1.13, 1.03-1.23) and SXT (OR 1.10, 1.01-1.19). Age was predictive for faecal E.
      coli resistance to amoxicillin (OR 1.02, 1.00-1.03), norfloxacin and
      ciprofloxacin (both OR 1.03, 1.01-1.06). In conclusion, in women with rUTI
      different determinants were found for urinary and faecal E. coli resistance.
      Previous antibiotic use and UTI history were associated with urine E. coli
      resistance and age was a predictor of faecal E. coli resistance. These
      associations could best be explained by cumulative antibiotic use.

PMID- 23166797
TI  - Hematopoietically-expressed homeobox gene three widely-evaluated polymorphisms
      and risk for diabetes: a meta-analysis.
AB  - BACKGROUND: The hematopoietically-expressed homeobox (HHEX) gene is identified as
      a promising candidate for type 2 diabetes by genome-wide association studies,
      triggering plenty of subsequent replications; however, the results are
      conflicting. We therefore conducted a meta-analysis of three widely-evaluated
      polymorphisms in HHEX gene and diabetes risk. METHODOLOGY/PRINCIPAL FINDINGS: A
      random-effects model was adopted irrespective of heterogeneity. Data and study
      quality were assessed in duplicate. There were 49 studies (cases/controls:
      57931/74658) for rs1111875, 18 studies (18227/30366) for rs5015480 and 26 studies
      (25725/30579) for rs7923837, respectively. Overall analyses indicated that
      rs1111875-C allele (odds ratio [OR] = 1.16; 95% confidence interval [CI]: 1.13
      1.2; P<0.0005), rs5015480-C allele (OR = 1.16; 95% CI: 1.06-1.26; P = 0.001) and
      rs7923837-G allele (OR = 1.18; 95% CI: 1.12-1.24; P<0.0005) conferred
      significantly increased risk for type 2 diabetes, yet accompanying moderate to
      strong evidence of heterogeneity. Despite vast divergence in allele
      distributions, subgroup analyses by ethnicity showed comparable risk estimates
      between Asians and Caucasians for three examined polymorphisms. Moreover, results
      of studies with hospital-based controls deviated greatly from that of all
      qualified studies, especially for rs7923837-G allele carrying a doubled risk (OR
      = 1.37 versus 1.18). Furthermore, when only large studies (>= 500 case-patients)
      were considered, risk effects were identical to the overall estimates for three
      examined polymorphisms. The Begg's funnel plot and Egger's test indicated low
      probability of publication bias. CONCLUSIONS: Our results provide clarification
      to the significant association of rs1111875, rs5015480 and rs7923837 in HHEX gene
      with type 2 diabetes.

PMID- 23166799
TI  - On the contribution of binocular disparity to the long-term memory for natural
      scenes.
AB  - Binocular disparity is a fundamental dimension defining the input we receive from
      the visual world, along with luminance and chromaticity. In a memory task
      involving images of natural scenes we investigate whether binocular disparity
      enhances long-term visual memory. We found that forest images studied in the
      presence of disparity for relatively long times (7s) were remembered better as
      compared to 2D presentation. This enhancement was not evident for other
      categories of pictures, such as images containing cars and houses, which are
      mostly identified by the presence of distinctive artifacts rather than by their
      spatial layout. Evidence from a further experiment indicates that observers do
      not retain a trace of stereo presentation in long-term memory.

PMID- 23166798
TI  - Sidestream smoke exposure increases the susceptibility of airway epithelia to
      adenoviral infection.
AB  - BACKGROUND: Although significant epidemiological evidence indicates that
      cigarette smoke exposure increases the incidence and severity of viral infection,
      the molecular mechanisms behind the increased susceptibility of the respiratory
      tract to viral pathogens are unclear. Adenoviruses are non-enveloped DNA viruses
      and important causative agents of acute respiratory disease. The Coxsackievirus
      and adenovirus receptor (CAR) is the primary receptor for many adenoviruses. We
      hypothesized that cigarette smoke exposure increases epithelial susceptibility to
      adenovirus infection by increasing the abundance of apical CAR. METHODOLOGY AND
      FINDINGS: Cultured human airway epithelial cells (CaLu-3) were used as a model to
      investigate the effect of sidestream cigarette smoke (SSS), mainstream cigarette
      smoke (MSS), or control air exposure on the susceptibility of polarized
      respiratory epithelia to adenoviral infection. Using a Cultex air-liquid
      interface exposure system, we have discovered novel differences in epithelial
      susceptibility between SSS and MSS exposures. SSS exposure upregulates an eight
      exon isoform of CAR and increases adenoviral entry from the apical surface whilst
      MSS exposure is similar to control air exposure. Additionally, the level of
      cellular glycogen synthase kinase 3beta (GSK3beta) is downregulated by SSS
      exposure and treatment with a specific GSK3beta inhibitor recapitulates the
      effects of SSS exposure on CAR expression and viral infection. CONCLUSIONS: This
      is the first time that SSS exposure has been shown to directly enhance the
      susceptibility of a polarized epithelium to infection by a common respiratory
      viral pathogen. This work provides a novel understanding of the impact of SSS on
      the burden of respiratory viral infections and may lead to new strategies to
      alter viral infections. Moreover, since GSK3beta inhibitors are under intense
      clinical investigation as therapeutics for a diverse range of diseases, studies
      such as these might provide insight to extend the use of clinically relevant
      therapeutics and increase the understanding of potential side effects.

PMID- 23166800
TI  - An FMRI study of the neural systems involved in visually cued auditory top-down
      spatial and temporal attention.
AB  - Top-down attention to spatial and temporal cues has been thoroughly studied in
      the visual domain. However, because the neural systems that are important for
      auditory top-down temporal attention (i.e., attention based on time interval
      cues) remain undefined, the differences in brain activity between directed
      attention to auditory spatial location (compared with time intervals) are
      unclear. Using fMRI (magnetic resonance imaging), we measured the activations
      caused by cue-target paradigms by inducing the visual cueing of attention to an
      auditory target within a spatial or temporal domain. Imaging results showed that
      the dorsal frontoparietal network (dFPN), which consists of the bilateral
      intraparietal sulcus and the frontal eye field, responded to spatial orienting of
      attention, but activity was absent in the bilateral frontal eye field (FEF)
      during temporal orienting of attention. Furthermore, the fMRI results indicated
      that activity in the right ventrolateral prefrontal cortex (VLPFC) was
      significantly stronger during spatial orienting of attention than during temporal
      orienting of attention, while the DLPFC showed no significant differences between
      the two processes. We conclude that the bilateral dFPN and the right VLPFC
      contribute to auditory spatial orienting of attention. Furthermore, specific
      activations related to temporal cognition were confirmed within the superior
      occipital gyrus, tegmentum, motor area, thalamus and putamen.

PMID- 23166801
TI  - Identification and re-evaluation of freshwater catfishes through DNA barcoding.
AB  - BACKGROUND: Catfishes are globally demanded as human food, angling sport and
      aquariums keeping thus are highly exploited all over the world. North-East India
      possess high abundance of catfishes and are equally exploited through decades.
      The strategies for conservation necessitate understanding the actual species
      composition, which is hampered due to sporadic descriptions of the species
      through traditional taxonomy. Therefore, actual catfish diversity in this region
      is important to be studied through the combined approach of morphological and
      molecular technique of DNA barcoding. METHODOLOGY/PRINCIPAL FINDINGS: Altogether
      75 native catfish specimens were collected from across the North-East India and
      their morphological features were compared with the taxonomic keys. The detailed
      taxonomic study identified 25 species belonging to 17 genera and 9 families. The
      cytochrome oxidase c subunit-I gene fragment were then sequenced from the samples
      in accordance with the standard DNA barcoding protocols. The sequences were
      compared with public databases, viz., GenBank and BOLD. Sequences developed in
      the current study and from databases of the same and related taxa were analyzed
      to calculate the congeneric and conspecific genetic divergences using Kimura 2
      parameter distance model, and a Neighbor Joining tree was created using software
      MEGA5.1. The DNA barcoding approach delineated 21 distinct species showing 4.33
      folds of difference between the nearest congeners. Four species, viz., Amblyceps
      apangi, Glyptothorax telchitta, G. trilineatus and Erethistes pusillus, showed
      high conspecific divergence; hence their identification through molecular
      approach remained inconclusive. On the other hand, the database sequences for
      three species, viz., Mystus horai, Bagarius yarrelli and Clarias batrachus,
      appeared mislabeled. CONCLUSION: The efficiency of DNA barcoding was reaffirmed
      from its success by easily identifying the major share (84%) of the studied
      catfish into 21 distinct species. The study contributed 27 new barcodes for 7
      species and confirmed the range expansion of 2 important species in NE India.

PMID- 23166802
TI  - Integration of a systems biological network analysis and QTL results for biomass
      heterosis in Arabidopsis thaliana.
AB  - To contribute to a further insight into heterosis we applied an integrative
      analysis to a systems biological network approach and a quantitative genetics
      analysis towards biomass heterosis in early Arabidopsis thaliana development. The
      study was performed on the parental accessions C24 and Col-0 and the reciprocal
      crosses. In an over-representation analysis it was tested if the overlap between
      the resulting gene lists of the two approaches is significantly larger than
      expected by chance. Top ranked genes in the results list of the systems
      biological analysis were significantly over-represented in the heterotic QTL
      candidate regions for either hybrid as well as regarding mid-parent and best
      parent heterosis. This suggests that not only a few but rather several genes that
      influence biomass heterosis are located within each heterotic QTL region.
      Furthermore, the overlapping resulting genes of the two integrated approaches
      were particularly enriched in biomass related pathways. A chromosome-wise over
      representation analysis gave rise to the hypothesis that chromosomes number 2 and
      4 probably carry a majority of the genes involved in biomass heterosis in the
      early development of Arabidopsis thaliana.

PMID- 23166803
TI  - Metabolic adaptations may counteract ventilatory adaptations of intermittent
      hypoxic exposure during submaximal exercise at altitudes up to 4000 m.
AB  - Intermittent hypoxic exposure (IHE) has been shown to induce aspects of altitude
      acclimatization which affect ventilatory, cardiovascular and metabolic responses
      during exercise in normoxia and hypoxia. However, knowledge on altitude-dependent
      effects and possible interactions remains scarce. Therefore, we determined the
      effects of IHE on cardiorespiratory and metabolic responses at different
      simulated altitudes in the same healthy subjects. Eight healthy male volunteers
      participated in the study and were tested before and 1 to 2 days after IHE (7 * 1
      hour at 4500 m). The participants cycled at 2 submaximal workloads (corresponding
      to 40% and 60% of peak oxygen uptake at low altitude) at simulated altitudes of
      2000 m, 3000 m, and 4000 m in a randomized order. Gas analysis was performed and
      arterial oxygen saturation, blood lactate concentrations, and blood gases were
      determined during exercise. Additionally baroreflex sensitivity, hypoxic and
      hypercapnic ventilatory response were determined before and after IHE. Hypoxic
      ventilatory response was increased after IHE (p<0.05). There were no altitude
      dependent changes by IHE in any of the determined parameters. However, blood
      lactate concentrations and carbon dioxide output were reduced; minute ventilation
      and arterial oxygen saturation were unchanged, and ventilatory equivalent for
      carbon dioxide was increased after IHE irrespective of altitude. Changes in
      hypoxic ventilatory response were associated with changes in blood lactate (r = 
      0.72, p<0.05). Changes in blood lactate correlated with changes in carbon dioxide
      output (r = 0.61, p<0.01) and minute ventilation (r = 0.54, p<0.01). Based on the
      present results it seems that the reductions in blood lactate and carbon dioxide
      output have counteracted the increased hypoxic ventilatory response. As a result
      minute ventilation and arterial oxygen saturation did not increase during
      submaximal exercise at simulated altitudes between 2000 m and 4000 m.

PMID- 23166804
TI  - Chromosomal and plasmid-encoded factors of Shigella flexneri induce secretogenic
      activity ex vivo.
AB  - Shigella flexneri is a Gram-negative, facultative intracellular pathogen that
      causes millions of cases of watery or bloody diarrhea annually, resulting in
      significant global mortality. Watery diarrhea is thought to arise in the jejunum,
      and subsequent bloody diarrhea occurs as a result of invasion of the colonic
      epithelium. Previous literature has demonstrated that Shigella encodes
      enterotoxins, both chromosomally and on the 220 kilobase virulence plasmid. The
      ShigellaEnterotoxins 1 and 2 (ShET1 and ShET2) have been shown to increase water
      accumulation in the rabbit ileal loop model. In addition, these toxins increase
      the short circuit current in rabbit tissue mounted in Ussing chambers, which is a
      model for the ion exchange that occurs during watery diarrhea. In this study, we
      sought to validate the use of mouse jejunum in Ussing chamber as an alternative,
      more versatile model to study bacterial pathogenesis. In the process, we also
      identified enterotoxins in addition to ShET1 and ShET2 encoded by S. flexneri.
      Through analysis of proteins secreted from wildtype bacteria and various deletion
      mutants, we have identified four factors responsible for enterotoxin activity:
      ShET1 and Pic, which are encoded on the chromosome; ShET2 (encoded by sen or
      ospD3), which requires the type-III secretion system for secretion; and SepA, an
      additional factor encoded on the virulence plasmid. The use of mouse jejunum
      serves as a reliable and reproducible model to identify the enterotoxins
      elaborated by enteric bacteria. Moreover, the identification of all Shigella
      proteins responsible for enterotoxin activity is vital to our understanding of
      Shigella pathogenicity and to our success in developing safe and effective
      vaccine candidates.

PMID- 23166805
TI  - Low prevalence of Pneumocystis pneumonia (PCP) but high prevalence of
      pneumocystis dihydropteroate synthase (dhps) gene mutations in HIV-infected
      persons in Uganda.
AB  - Pneumocystis jirovecii pneumonia (PCP) is an important opportunistic infection in
      patients infected with HIV, but its burden is incompletely characterized in those
      areas of sub-Saharan Africa where HIV is prevalent. We explored the prevalence of
      both PCP in HIV-infected adults admitted with pneumonia to a tertiary-care
      hospital in Uganda and of putative P. jirovecii drug resistance by mutations in
      fungal dihydropteroate synthase (dhps) and dihydrofolate reductase (dhfr). In 129
      consecutive patients with sputum smears negative for mycobacteria, 5 (3.9%) were
      diagnosed with PCP by microscopic examination of Giemsa-stained bronchoalveolar
      lavage fluid. Concordance was 100% between Giemsa stain and PCR (dhps and dhfr).
      PCP was more prevalent in patients newly-diagnosed with HIV (11.4%) than in
      patients with known HIV (1.1%; p = 0.007). Mortality at 2 months after discharge
      was 29% overall: 28% among PCP-negative patients, and 60% (3 of 5) among PCP
      positive patients. In these 5 fungal isolates and an additional 8 from
      consecutive cases of PCP, all strains harbored mutant dhps haplotypes; all 13
      isolates harbored the P57S mutation in dhps, and 3 (23%) also harbored the T55A
      mutation. No non-synonymous dhfr mutations were detected. PCP is an important
      cause of pneumonia in patients newly-diagnosed with HIV in Uganda, is associated
      with high mortality, and putative molecular evidence of drug resistance is
      prevalent. Given the reliability of field diagnosis in our cohort, future studies
      in sub-Saharan Africa can investigate the clinical impact of these genotypes.

PMID- 23166806
TI  - Feeding period restriction alters the expression of peripheral circadian rhythm
      genes without changing body weight in mice.
AB  - Accumulating evidence suggests that the circadian clock is closely associated
      with metabolic regulation. However, whether an impaired circadian clock is a
      direct cause of metabolic dysregulation such as body weight gain is not clearly
      understood. In this study, we demonstrate that body weight gain in mice is not
      significantly changed by restricting feeding period to daytime or nighttime. The
      expression of peripheral circadian clock genes was altered by feeding period
      restriction, while the expression of light-regulated hypothalamic circadian clock
      genes was unaffected by either a normal chow diet (NCD) or a high-fat diet (HFD).
      In the liver, the expression pattern of circadian clock genes, including Bmal1,
      Clock, and Per2, was changed by different feeding period restrictions. Moreover,
      the expression of lipogenic genes, gluconeogenic genes, and fatty acid oxidation
      related genes in the liver was also altered by feeding period restriction. Given
      that feeding period restriction does not affect body weight gain with a NCD or
      HFD, it is likely that the amount of food consumed might be a crucial factor in
      determining body weight. Collectively, these data suggest that feeding period
      restriction modulates the expression of peripheral circadian clock genes, which
      is uncoupled from light-sensitive hypothalamic circadian clock genes.

PMID- 23166807
TI  - Treg cell resistance to apoptosis in DNA vaccination for experimental autoimmune
      encephalomyelitis treatment.
AB  - BACKGROUND: Regulatory T (Treg) cells can be induced with DNA vaccinations and
      protect mice from the development of experimental autoimmune encephalomyelitis
      (EAE), a mouse model of multiple sclerosis (MS). Tacrolimus (FK506) has been
      shown to have functions on inducing immunosuppression and augmenting apoptosis of
      pathologic T cells in autoimmune disease. Here we examined the therapeutic effect
      of DNA vaccine in conjunction with FK506 on EAE. METHODOLOGY/PRINCIPAL FINDINGS:
      After EAE induction, C57BL/6 mice were treated with DNA vaccine in conjunction
      with FK506. Functional Treg cells were induced in treated EAE mice and suppressed
      Th1 and Th17 cell responses. Infiltrated CD4 T cells were reduced while Treg
      cells were induced in spinal cords of treated EAE mice. Remarkably, the activated
      CD4 T cells augmented apoptosis, but the induced Treg cells resisted apoptosis in
      treated EAE mice, resulting in alleviation of clinical EAE severity.
      CONCLUSIONS/SIGNIFICANCE: DNA vaccine in conjunction with FK506 treatment
      ameliorates EAE by enhancing apoptosis of CD4 T cells and resisting apoptosis of
      induced Treg cells. Our findings implicate the potential of tolerogenic DNA
      vaccines for treating MS.

PMID- 23166808
TI  - Poor sleep in patients with multiple sclerosis.
AB  - BACKGROUND: Poor sleep is a frequent symptom in patients with multiple sclerosis
      (MS). Sleep may be influenced by MS-related symptoms and adverse effects from
      immunotherapy and symptomatic medications. We aimed to study the prevalence of
      poor sleep and the influence of socio-demographic and clinical factors on sleep
      quality in MS- patients. METHODS: A total of 90 MS patients and 108 sex-and age-
      matched controls were included in a questionnaire survey. Sleep complaints were
      evaluated by Pittsburgh Sleep Quality Index (PSQI) and a global PSQI score was
      used to separate good sleepers (<= 5) from poor sleepers (>5). Excessive daytime
      sleepiness, the use of immunotherapy and antidepressant drugs, symptoms of pain,
      depression, fatigue and MS-specific health related quality of life were
      registered. Results were compared between patients and controls and between good
      and poor sleepers among MS patients. RESULTS: MS patients reported a higher mean
      global PSQI score than controls (8.6 vs. 6.3, p = 0.001), and 67.1% of the MS
      patients compared to 43.9% of the controls (p = 0.002) were poor sleepers. Pain
      (p = 0.02), fatigue (p = 0.001), depression (p = 0.01) and female gender (p =
      0.04) were associated with sleep disturbance. Multivariate analyses showed that
      female gender (p = 0.02), use of immunotherapy (p = 005) and a high psychological
      burden of MS (p = 0.001) were associated with poor sleep among MS patients.
      CONCLUSIONS: Poor sleep is common in patients with MS. Early identification and
      treatment of modifiable risk factors may improve sleep and quality of life in MS.

PMID- 23166809
TI  - A comprehensive analysis of interaction and localization of Arabidopsis SKP1-like
      (ASK) and F-box (FBX) proteins.
AB  - F-Box (FBX) proteins are encoded by a multigene family present in major lineages
      of eukaryotes. A number of FBX proteins are shown to be subunits of SCF complex,
      a type of E3 ligases composed of SKP1, CULLIN, FBX and RBX1 proteins. The
      Arabidopsis SKP-LIKE (ASK) proteins are also members of a family and some of them
      interact with FBX proteins directly. To clarify how FBX and ASK proteins combine,
      we carried out a large-scale interaction analysis between FBX and ASK proteins
      using yeast two-hybrid assay (Y2H) in Arabidopsis thaliana. FBX proteins randomly
      chosen from those proteins that interacted with more than one ASK protein were
      further analyzed for their subcellular localization and in vivo interaction with
      ASK proteins. Furthermore, the expression profiles of FBX and ASK genes were
      compared. This work reveals that FBX proteins had a preference for interacting
      with ASK proteins depending on the domains they contain such as the FBX
      associated (FBA) domain, the Kelch domain and leucine rich repeat (LRR). In
      addition, it was found that a single FBX protein could form multiple SCF
      complexes by interacting with several ASK proteins in many cases. Furthermore, it
      was suggested that the variation of SCF complexes were especially abundant in
      tissues related to male gametophyte and seed development. More than half of the
      FBX proteins studied did not interact with any of the ASK proteins, implying the
      necessity for certain regulations for their interaction in vivo and/or distinct
      roles from subunits of the SCF complex.

PMID- 23166810
TI  - The O2, pH and Ca2+ microenvironment of benthic foraminifera in a high CO2 world.
AB  - Ocean acidification (OA) can have adverse effects on marine calcifiers. Yet,
      phototrophic marine calcifiers elevate their external oxygen and pH
      microenvironment in daylight, through the uptake of dissolved inorganic carbon
      (DIC) by photosynthesis. We studied to which extent pH elevation within their
      microenvironments in daylight can counteract ambient seawater pH reductions, i.e.
      OA conditions. We measured the O(2) and pH microenvironment of four
      photosymbiotic and two symbiont-free benthic tropical foraminiferal species at
      three different OA treatments (~432, 1141 and 2151 uatm pCO(2)). The O(2)
      concentration difference between the seawater and the test surface (DeltaO(2))
      was taken as a measure for the photosynthetic rate. Our results showed that O(2)
      and pH levels were significantly higher on photosymbiotic foraminiferal surfaces
      in light than in dark conditions, and than on surfaces of symbiont-free
      foraminifera. Rates of photosynthesis at saturated light conditions did not
      change significantly between OA treatments (except in individuals that exhibited
      symbiont loss, i.e. bleaching, at elevated pCO(2)). The pH at the cell surface
      decreased during incubations at elevated pCO(2), also during light incubations.
      Photosynthesis increased the surface pH but this increase was insufficient to
      compensate for ambient seawater pH decreases. We thus conclude that
      photosynthesis does only partly protect symbiont bearing foraminifera against OA.

PMID- 23166811
TI  - Function annotation of hepatic retinoid x receptor alpha based on genome-wide DNA
      binding and transcriptome profiling.
AB  - BACKGROUND: Retinoid x receptor alpha (RXRalpha) is abundantly expressed in the
      liver and is essential for the function of other nuclear receptors. Using
      chromatin immunoprecipitation sequencing and mRNA profiling data generated from
      wild type and RXRalpha-null mouse livers, the current study identifies the bona
      fide hepatic RXRalpha targets and biological pathways. In addition, based on
      binding and motif analysis, the molecular mechanism by which RXRalpha regulates
      hepatic genes is elucidated in a high-throughput manner. PRINCIPAL FINDINGS:
      Close to 80% of hepatic expressed genes were bound by RXRalpha, while 16% were
      expressed in an RXRalpha-dependent manner. Motif analysis predicted direct repeat
      with a spacer of one nucleotide as the most prevalent RXRalpha binding site. Many
      of the 500 strongest binding motifs overlapped with the binding motif of specific
      protein 1. Biological functional analysis of RXRalpha-dependent genes revealed
      that hepatic RXRalpha deficiency mainly resulted in up-regulation of steroid and
      cholesterol biosynthesis-related genes and down-regulation of translation- as
      well as anti-apoptosis-related genes. Furthermore, RXRalpha bound to many genes
      that encode nuclear receptors and their cofactors suggesting the central role of
      RXRalpha in regulating nuclear receptor-mediated pathways. CONCLUSIONS: This
      study establishes the relationship between RXRalpha DNA binding and hepatic gene
      expression. RXRalpha binds extensively to the mouse genome. However, DNA binding
      does not necessarily affect the basal mRNA level. In addition to metabolism,
      RXRalpha dictates the expression of genes that regulate RNA processing,
      translation, and protein folding illustrating the novel roles of hepatic RXRalpha
      in post-transcriptional regulation.

PMID- 23166812
TI  - A quantitative proteomic profile of the Nrf2-mediated antioxidant response of
      macrophages to oxidized LDL determined by multiplexed selected reaction
      monitoring.
AB  - The loading of macrophages with oxidized low density lipoprotein (LDL) is a key
      part of the initiation and progression of atherosclerosis. Oxidized LDL contains
      a wide ranging set of toxic species, yet the molecular events that allow
      macrophages to withstand loading with these toxic species are not completely
      characterized. The transcription factor nuclear factor (erythroid-derived 2)-like
      2 (Nrf2) is a master regulator of the cellular stress response. However, the
      specific parts of the Nrf2-dependent stress response are diverse, with both
      tissue- and treatment-dependent components. The goal of these experiments was to
      develop and use a quantitative proteomic approach to characterize the Nrf2
      dependent response in macrophages to oxidized LDL. Cultured mouse macrophages,
      the J774 macrophage-like cell line, were treated with a combination of oxidized
      LDL, the Nrf2-stabilizing reagent tert- butylhydroquinone (tBHQ), and/or Nrf2
      siRNA. Protein expression was determined using a quantitative proteomics assay
      based on selected reaction monitoring. The assay was multiplexed to monitor a set
      of 28 antioxidant and stress response proteins, 6 housekeeping proteins, and 1
      non-endogenous standard protein. The results have two components. The first
      component is the validation of the multiplexed, quantitative proteomics assay.
      The assay is shown to be fundamentally quantitative, precise, and accurate. The
      second component is the characterization of the Nrf2-mediated stress response.
      Treatment with tBHQ and/or Nrf2 siRNA gave statistically significant changes in
      the expression of a subset of 11 proteins. Treatment with oxidized LDL gave
      statistically significant increases in the expression of 7 of those 11 proteins
      plus one additional protein. All of the oxLDL-mediated increases were attenuated
      by Nrf2 siRNA. These results reveal a specific, multifaceted response of the foam
      cells to the incoming toxic oxidized LDL.

PMID- 23166814
TI  - A rapid screening assay to search for phosphorylated proteins in tissue extracts.
AB  - Reversible protein phosphorylation is an essential mechanism in the regulation of
      diverse biological processes, nonetheless is frequently altered in disease. As
      most phosphoproteome studies are based on optimized in-vitro cell culture studies
      new methods are in need to improve de novo identification and characterization of
      phosphoproteins in extracts from tissues. Here, we describe a rapid and reliable
      method for the detection of phosphoproteins in tissue extract based on an
      experimental strategy that employs 1D and 2D SDS PAGE, Western immunoblotting of
      phosphoproteins, in-gel protease digestion and enrichment of phosphorpeptides
      using metal oxide affinity chromatography (MOAC). Subsequently, phosphoproteins
      are identified by MALDI-TOF-MS/MS with the CHCA-TL or DHB ML sample matrix
      preparation method and further characterized by various bioinformatic software
      tools to search for candidate kinases and phosphorylation-dependent binding
      motifs. The method was applied to mouse lung tissue extracts and resulted in an
      identification of 160 unique phosphoproteins. Notably, TiO(2) enrichment of
      pulmonary protein extracts resulted in an identification of additional 17
      phosphoproteins and 20 phosphorylation sites. By use of MOAC, new phosphorylation
      sites were identified as evidenced for the advanced glycosylation end product
      specific receptor. So far this protein was unknown to be phosphorylated in lung
      tissue of mice. Overall the developed methodology allowed efficient and rapid
      screening of phosphorylated proteins and can be employed as a general
      experimental strategy for an identification of phosphoproteins in tissue
      extracts.

PMID- 23166813
TI  - The WSTF-ISWI chromatin remodeling complex transiently associates with the human
      inactive X chromosome during late S-phase prior to BRCA1 and gamma-H2AX.
AB  - Replicating the genome prior to each somatic cell division not only requires
      precise duplication of the genetic information, but also accurately
      reestablishing the epigenetic signatures that instruct how the genetic material
      is to be interpreted in the daughter cells. The mammalian inactive X chromosome
      (Xi), which is faithfully inherited in a silent state in each daughter cell,
      provides an excellent model of epigenetic regulation. While much is known about
      the early stages of X chromosome inactivation, much less is understood with
      regards to retaining the Xi chromatin through somatic cell division. Here we
      report that the WSTF-ISWI chromatin remodeling complex (WICH) associates with the
      Xi during late S-phase as the Xi DNA is replicated. Elevated levels of WICH at
      the Xi is restricted to late S-phase and appears before BRCA1 and gamma-H2A.X.
      The sequential appearance of WICH and BRCA1/gamma-H2A.X implicate each as
      performing important but distinct roles in the maturation and maintenance of
      heterochromatin at the Xi.

PMID- 23166815
TI  - Crustacean hyperglycemic hormone (cHH) as a modulator of aggression in crustacean
      decapods.
AB  - Biogenic amines, particularly serotonin, are recognised to play an important role
      in controlling the aggression of invertebrates, whereas the effect of
      neurohormones is still underexplored. The crustacean Hyperglycemic Hormone (cHH)
      is a multifunctional member of the eyestalk neuropeptide family. We expect that
      this neuropeptide influences aggression either directly, by controlling its
      expression, or indirectly, by mobilizing the energetic stores needed for the
      increased activity of an animal. Our study aims at testing such an influence and
      the possible reversion of hierarchies in the red swamp crayfish, Procambarus
      clarkii, as a model organism. Three types of pairs of similarly sized males were
      formed: (1) 'control pairs' (CP, n = 8): both individuals were injected with a
      phosphate saline solution (PBS); (2) 'reinforced pairs' (RP, n = 9): the alpha
      alone was injected with native cHH, and the beta with PBS; (3) 'inverted pairs'
      (IP, n = 9): the opposite of (2). We found that, independently of the crayfish's
      prior social experience, cHH injections induced (i) the expression of dominance
      behaviour, (ii) higher glycemic levels, and (iii) lower time spent motionless. In
      CP and RP, fight intensity decreased with the establishment of dominance. On the
      contrary, in IP, betas became increasingly likely to initiate and escalate fights
      and, consequently, increased their dominance till a temporary reversal of the
      hierarchy. Our results demonstrate, for the first time, that, similarly to
      serotonin, cHH enhances individual aggression, up to reverse, although
      transitorily, the hierarchical rank. New research perspectives are thus opened in
      our intriguing effort of understanding the role of cHH in the modulation of
      agonistic behaviour in crustaceans.

PMID- 23166816
TI  - Wolbachia-induced aae-miR-12 miRNA negatively regulates the expression of MCT1
      and MCM6 genes in Wolbachia-infected mosquito cell line.
AB  - BACKGROUND: Best recognized for its role in manipulating host reproduction, the
      parasitic gram-negative Wolbachia pipientis is known to colonize a wide range of
      invertebrates. The endosymbiotic bacterium has recently been shown to cause a
      life-shortening effect as well as inhibiting replication of arboviruses in Aedes
      aegypti; although the molecular mechanisms behind these effects are largely
      unknown. MicroRNAs (miRNAs) have been determined to have a wide range of roles in
      regulating gene expression in eukaryotes. A recent study showed that several A.
      aegypti mosquito miRNAs are differentially expressed when infected with
      Wolbachia. METHODOLOGY/PRINCIPAL FINDINGS: Based on the prior knowledge that one
      of these miRNAs, aae-miR-12, is differentially expressed in mosquitoes infected
      with Wolbachia, we aimed to determine any significance of this mediation. We also
      set out to characterize the target genes of this miRNA in the A. aegpyti genome.
      Bioinformatic approaches predicted a list of potential target genes and
      subsequent functional analyses confirmed that two of these, DNA replication
      licensing (MCM6) and monocarboxylate transporter (MCT1), are under the regulative
      control of aae-miR-12. We also demonstrated that aae-miR-12 is critical in the
      persistence of Wolbachia in the host cell. CONCLUSIONS/SIGNIFICANCE: Our study
      has identified two target genes of aae-miR-12, a differentially expressed
      mosquito miRNA in Wolbachia-infected cells, and determined that the miRNA affects
      Wolbachia density in the host cells.

PMID- 23166817
TI  - Peak systolic velocity of superior thyroid artery for the differential diagnosis
      of thyrotoxicosis.
AB  - AIM: The differentiation of destruction-induced thyrotoxicosis and Graves'
      disease (GD) is of great importance for selection of proper therapy. Radioactive
      iodine uptake (RAIU) is the gold standard for differentiating these two
      conditions but its application has remained somewhat limited. Thyroid color
      Doppler flow sonography (CDFS) is a potential alternative of RAIU but more
      supporting evidence is warranted. In the present study, a standard operative
      procedure was developed to measure the mean peak systolic velocity of superior
      thyroid artery (STA-PSV) and evaluate its role in the differential diagnosis of
      thyrotoxicosis. METHODS: A total of 135 patients with untreated thyrotoxicosis
      were enrolled into one retrospective study (GD, n = 103; thyroiditis, n = 32) and
      another prospective study recruited 169 patients (GD, n = 118; thyroiditis, n =
      51). Thirty normal controls were also enrolled. Thyroid function, anti-TSH
      receptor antibody (TRAb), RAIU, CFDS of thyroid and STA-PSV were performed for
      each patient. Receiver operator curve (ROC) was used to evaluate the diagnostic
      value of STA-PSV in a retrospective study so as to seek the optimal cutoff point.
      Then the cutoff point value was used to validate its diagnostic value in a
      prospective study and in another thyrotoxicosis population. RESULTS: STA-PSV of
      GD was significantly higher than that of thyroiditis in both retrospective and
      prospective studies. The area under the ROC curve of mean STA-PSV was 0.8799 and
      0.9447 in the retrospective and prospective studies respectively. If a mean STA
      PSV cutoff point of 50.5 cm/s was set from the retrospective analysis for the
      prospective study, the sensitivity and specificity in distinguishing GD from
      thyroiditis were 81.04% and 96.08% respectively. Mean STA-PSV and TRAb had
      similar area under ROC. The coefficients of variation in STA-PSV measurement were
      lower than 10% for the euthyroid, thyroiditis and GD groups. CONCLUSIONS: STA-PSV
      is a feasible supplement alternative of RAIU for differentiating the causes of
      thyrotoxicosis.

PMID- 23166818
TI  - Parameter tuning patterns for random graph coloring with quantum annealing.
AB  - Quantum annealing is a combinatorial optimization technique inspired by quantum
      mechanics. Here we show that a spin model for the k-coloring of large dense
      random graphs can be field tuned so that its acceptance ratio diverges during
      Monte Carlo quantum annealing, until a ground state is reached. We also find that
      simulations exhibiting such a diverging acceptance ratio are generally more
      effective than those tuned to the more conventional pattern of a declining and/or
      stagnating acceptance ratio. This observation facilitates the discovery of
      solutions to several well-known benchmark k-coloring instances, some of which
      have been open for almost two decades.

PMID- 23166819
TI  - Ambiguity, ambivalence, and apprehensions of taking HIV-1 pre-exposure
      prophylaxis among male couples in San Francisco: a mixed methods study.
AB  - OBJECTIVE: We conducted a mixed-methods study to examine serodiscordant and
      seroconcordant (HIV-positive/HIV-positive) male couples' PrEP awareness, concerns
      regarding health care providers offering PrEP to the community, and correlates of
      PrEP uptake by the HIV-negative member of the couple. DESIGN: Qualitative sub
      study included one-on-one interviews to gain a deeper understanding of
      participants' awareness of and experiences with PrEP and concerns regarding
      health care providers offering PrEP to men who have sex with men (MSM).
      Quantitative analyses consisted of a cross-sectional study in which participants
      were asked about the likelihood of PrEP uptake by the HIV-negative member of the
      couple and level of agreement with health care providers offering PrEP to anyone
      requesting it. METHODS: We used multivariable regression to examine associations
      between PrEP questions and covariates of interest and employed an inductive
      approach to identify key qualitative themes. RESULTS: Among 328 men (164
      couples), 62% had heard about PrEP, but approximately one-quarter were mistaking
      it with post-exposure prophylaxis. The majority of participants had low
      endorsement of PrEP uptake and 40% were uncertain if health care providers should
      offer PrEP to anyone requesting it. Qualitative interviews with 32 men suggest
      that this uncertainty likely stems from concerns regarding increased risk
      compensation. Likelihood of future PrEP uptake by the HIV-negative member of the
      couple was positively associated with unprotected insertive anal intercourse but
      negatively correlated with unprotected receptive anal intercourse. CONCLUSIONS:
      Findings suggest that those at greatest risk may not be receptive of PrEP. Those
      who engage in moderate risk express more interest in PrEP; however, many voice
      concerns of increased risk behavior in tandem with PrEP use. Results indicate a
      need for further education of MSM communities and the need to determine
      appropriate populations in which PrEP can have the highest impact.

PMID- 23166820
TI  - Increased risk of virologic rebound in patients on antiviral therapy with a
      detectable HIV load <48 copies/mL.
AB  - We investigated the independent effects of HIV-1 "target not detected"
      measurements versus those that were detectable but below the limit of
      quantification by Taqman RT-PCR assay on subsequent viral rebound as there are
      conflicting data regarding the clinical implications of arbitrary or isolated low
      level viremia. Cox proportional hazard regression modeling was used to
      investigate the independent effects of the first HIV-1 load measurement after
      introduction of the Taqman RT-PCR assay (time-point 0 [T0]), pre-T0 viral loads,
      CD4 T cell count, race/ethnicity, gender, age and NNRTI use on risk of a
      confirmed VL >50, >200, >400 and >1000 copies/mL at 22 months follow-up in
      analyses of all patients and propensity-matched baseline cohorts. 778 patients
      had a viral load that was either not detected by RT-PCR (N = 596) or detectable,
      but below the limit of quantification (N = 182) at T0. Detectable viremia, lower
      T0 CD4 count, decreased age, and having detectable or unknown VL within a year
      prior to T0 were each associated with viral rebound to >50, >200 and >400
      copies/mL. Overall failure rates were low and <5.5% of all patients had confirmed
      VL >1000 copies/mL. A majority of patients with rebound >200 copies/mL
      subsequently re-suppressed (28 of 53). A detectable VL <48 copies/mL was
      independently and significantly associated with subsequent viral rebound, and is
      cause for clinical concern.

PMID- 23166821
TI  - Phosphorylation of DeltaNp63alpha via a novel TGFbeta/ALK5 signaling mechanism
      mediates the anti-clonogenic effects of TGFbeta.
AB  - Genetic analysis of TP63 implicates DeltaNp63 isoforms in preservation of
      replicative capacity and cellular lifespan within adult stem cells.
      DeltaNp63alpha is also an oncogene and survival factor that mediates therapeutic
      resistance in squamous carcinomas. These diverse activities are the result of
      genetic and functional interactions between TP63 and an array of morphogenic and
      morphostatic signals that govern tissue and tumor stasis, mitotic polarity, and
      cell fate; however the cellular signals that account for specific functions of
      TP63 are incompletely understood. To address this we sought to identify signaling
      pathways that regulate expression, stability or activity of DeltaNp63alpha. An
      siRNA-based screen of the human kinome identified the Type 1 TGFbeta receptor,
      ALK5, as the kinase required for phosphorylation of DeltaNp63alpha at Serine
      66/68 (S66/68). This activity is TGFbeta-dependent and sensitive to either ALK5
      directed siRNA or the ALK5 kinase inhibitor A83-01. Mechanistic studies support a
      model in which ALK5 is proteolytically cleaved at the internal juxtamembrane
      region resulting in the translocation of the C-terminal ALK5-intracellular kinase
      domain (ALK5(IKD)). In this study, we demonstrate that ALK5-mediated
      phosphorylation of DeltaNp63alpha is required for the anti-clonogenic effects of
      TGFBeta and ectopic expression of ALK5(IKD) mimics these effects. Finally, we
      present evidence that ultraviolet irradiation-mediated phosphorylation of
      DeltaNp63alpha is sensitive to ALK5 inhibitors. These findings identify a non
      canonical TGFbeta-signaling pathway that mediates the anti-clonogenic effects of
      TGFbeta and the effects of cellular stress via DeltaNp63alpha phosphorylation.

PMID- 23166822
TI  - Survey of endosymbionts in the Diaphorina citri metagenome and assembly of a
      Wolbachia wDi draft genome.
AB  - Diaphorina citri (Hemiptera: Psyllidae), the Asian citrus psyllid, is the insect
      vector of Ca. Liberibacter asiaticus, the causal agent of citrus greening
      disease. Sequencing of the D. citri metagenome has been initiated to gain better
      understanding of the biology of this organism and the potential roles of its
      bacterial endosymbionts. To corroborate candidate endosymbionts previously
      identified by rDNA amplification, raw reads from the D. citri metagenome sequence
      were mapped to reference genome sequences. Results of the read mapping provided
      the most support for Wolbachia and an enteric bacterium most similar to
      Salmonella. Wolbachia-derived reads were extracted using the complete genome
      sequences for four Wolbachia strains. Reads were assembled into a draft genome
      sequence, and the annotation assessed for the presence of features potentially
      involved in host interaction. Genome alignment with the complete sequences
      reveals membership of Wolbachia wDi in supergroup B, further supported by
      phylogenetic analysis of FtsZ. FtsZ and Wsp phylogenies additionally indicate
      that the Wolbachia strain in the Florida D. citri isolate falls into a sub-clade
      of supergroup B, distinct from Wolbachia present in Chinese D. citri isolates,
      supporting the hypothesis that the D. citri introduced into Florida did not
      originate from China.

PMID- 23166825
TI  - Spontaneous reperfusion after in situ thromboembolic stroke in mice.
AB  - Injection of thrombin into the middle cerebral artery (MCA) of mice has been
      proposed as a new model of thromboembolic stroke. The present study used
      sequential multiparametric Magnetic Resonance Imaging (MRI), including Magnetic
      Resonance Angiography (MRA), Diffusion-Weighted Imaging (DWI) and Perfusion
      Weighted Imaging (PWI), to document MCA occlusion, PWI-DWI mismatch, and lesion
      development. In the first experiment, complete MCA occlusion and reproducible
      hypoperfusion were obtained in 85% of animals during the first hour after stroke
      onset. In the second experiment, 80% of animals showed partial to complete
      reperfusion during a three-hour follow-up. Spontaneous reperfusion thus
      contributed to the variability in ischemic volume in this model. The study
      confirmed the value of the model for evaluating new thrombolytic treatments, but
      calls for extended MRI follow-up at the acute stage in therapeutic studies.

PMID- 23166824
TI  - Hyaluronan (HA) interacting proteins RHAMM and hyaluronidase impact prostate
      cancer cell behavior and invadopodia formation in 3D HA-based hydrogels.
AB  - To study the individual functions of hyaluronan interacting proteins in prostate
      cancer (PCa) motility through connective tissues, we developed a novel three
      dimensional (3D) hyaluronic acid (HA) hydrogel assay that provides a flexible,
      quantifiable, and physiologically relevant alternative to current methods.
      Invasion in this system reflects the prevalence of HA in connective tissues and
      its role in the promotion of cancer cell motility and tissue invasion, making the
      system ideal to study invasion through bone marrow or other HA-rich connective
      tissues. The bio-compatible cross-linking process we used allows for direct
      encapsulation of cancer cells within the gel where they adopt a distinct, cluster
      like morphology. Metastatic PCa cells in these hydrogels develop fingerlike
      structures, "invadopodia", consistent with their invasive properties. The number
      of invadopodia, as well as cluster size, shape, and convergence, can provide a
      quantifiable measure of invasive potential. Among candidate hyaluronan
      interacting proteins that could be responsible for the behavior we observed, we
      found that culture in the HA hydrogel triggers invasive PCa cells to
      differentially express and localize receptor for hyaluronan mediated motility
      (RHAMM)/CD168 which, in the absence of CD44, appears to contribute to PCa
      motility and invasion by interacting with the HA hydrogel components. PCa cell
      invasion through the HA hydrogel also was found to depend on the activity of
      hyaluronidases. Studies shown here reveal that while hyaluronidase activity is
      necessary for invadopodia and inter-connecting cluster formation, activity alone
      is not sufficient for acquisition of invasiveness to occur. We therefore suggest
      that development of invasive behavior in 3D HA-based systems requires development
      of additional cellular features, such as activation of motility associated
      pathways that regulate formation of invadopodia. Thus, we report development of a
      3D system amenable to dissection of biological processes associated with cancer
      cell motility through HA-rich connective tissues.

PMID- 23166823
TI  - Helicobacter pylori colonization ameliorates glucose homeostasis in mice through
      a PPAR gamma-dependent mechanism.
AB  - BACKGROUND: There is an inverse secular trend between the incidence of obesity
      and gastric colonization with Helicobacter pylori, a bacterium that can affect
      the secretion of gastric hormones that relate to energy homeostasis. H. pylori
      strains that carry the cag pathogenicity island (PAI) interact more intimately
      with gastric epithelial cells and trigger more extensive host responses than cag(
      ) strains. We hypothesized that gastric colonization with H. pylori strains
      differing in cag PAI status exert distinct effects on metabolic and inflammatory
      phenotypes. METHODOLOGY/PRINCIPAL FINDINGS: To test this hypothesis, we examined
      metabolic and inflammatory markers in db/db mice and mice with diet-induced
      obesity experimentally infected with isogenic forms of H. pylori strain 26695:
      the cag PAI wild-type and its cag PAI mutant strain 99-305. H. pylori
      colonization decreased fasting blood glucose levels, increased levels of leptin,
      improved glucose tolerance, and suppressed weight gain. A response found in both
      wild-type and mutant H. pylori strain-infected mice included decreased white
      adipose tissue macrophages (ATM) and increased adipose tissue regulatory T cells
      (Treg) cells. Gene expression analyses demonstrated upregulation of gastric PPAR
      gamma-responsive genes (i.e., CD36 and FABP4) in H. pylori-infected mice. The
      loss of PPAR gamma in immune and epithelial cells in mice impaired the ability of
      H. pylori to favorably modulate glucose homeostasis and ATM infiltration during
      high fat feeding. CONCLUSIONS/SIGNIFICANCE: Gastric infection with some commensal
      strains of H. pylori ameliorates glucose homeostasis in mice through a PPAR gamma
      dependent mechanism and modulates macrophage and Treg cell infiltration into the
      abdominal white adipose tissue.

PMID- 23166826
TI  - Volumetric MRI markers and predictors of disease activity in early multiple
      sclerosis: a longitudinal cohort study.
AB  - OBJECTIVES: To compare clinical and MRI parameters between patients with
      clinically isolated syndrome and those converting to clinically definite multiple
      sclerosis within 2 years, to identify volumetric MRI predictors of this
      conversion and to assess effect of early relapses. METHODS: The SET study
      comprised 220 patients with clinically isolated syndrome treated with interferon
      beta (mean age, 29 years; Expanded Disability Status Scale, 1.5). Three patients
      with missing data were excluded from the analysis. Physical disability, time to
      clinically definite multiple sclerosis and volumetric MRI data were recorded for
      2 years. RESULTS: Patients reaching clinically definite multiple sclerosis showed
      impaired recovery of neurological function, faster decrease in corpus callosum
      cross-sectional area, higher T2 lesion volume and more contrast-enhancing
      lesions. Six-month decrease in corpus callosum cross-sectional area (>= 1%) and
      baseline T2 lesion volume (>= 5 cm(3)) predicted clinically definite multiple
      sclerosis within 2 years (hazard ratios 2.5 and 1.8, respectively). Of 22
      patients fulfilling both predictive criteria, 83% reached clinically definite
      multiple sclerosis (hazard ratio 6.5). More relapses were associated with poorer
      recovery of neurological function and accelerated brain atrophy. CONCLUSIONS:
      Neurological impairment is more permanent, brain atrophy is accelerated and focal
      inflammatory activity is greater in patients converting to clinically definite
      multiple sclerosis. Six-month corpus callosum atrophy and baseline T2 lesion
      volume jointly help predict individual risk of clinically definite multiple
      sclerosis. Early relapses contribute to permanent damage of the central nervous
      system.

PMID- 23166827
TI  - Hydrogen sulfide in paraventricular nucleus enhances sympathetic activity and
      cardiac sympathetic afferent reflex in chronic heart failure rats.
AB  - BACKGROUND: Intracerebroventricular infusion of NaHS, a hydrogen sulfide (H(2)S)
      donor, increased mean arterial pressure (MAP). This study was designed to
      determine the roles of H(2)S in the paraventricular nucleus (PVN) in modulating
      sympathetic activity and cardiac sympathetic afferent reflex (CSAR) in chronic
      heart failure (CHF). METHODOLOGY/PRINCIPAL FINDINGS: CHF was induced by left
      descending coronary artery ligation in rats. Renal sympathetic nerve activity
      (RSNA) and MAP were recorded under anesthesia. CSAR was evaluated by the RSNA and
      MAP responses to epicardial application of capsaicin. PVN microinjection of low
      doses of a H(2)S donor, GYY4137 (0.01 and 0.1 nmol), had no significant effects
      on RSNA, MAP and CSAR. High doses of GYY4137 (1, 2 and 4 nmol) increased baseline
      RSNA, MAP and heart rate (HR), and enhanced CSAR. The effects were greater in CHF
      rats than sham-operated rats. A cystathionine-beta-synthase (CBS) inhibitor,
      hydroxylamine (HA) in PVN had no significant effect on the RSNA, MAP and CSAR.
      CBS activity and H(2)S level in the PVN were decreased in CHF rats. No
      significant difference in CBS level in PVN was found between sham-operated rats
      and CHF rats. Stimulation of cardiac sympathetic afferents with capsaicin
      decreased CBS activity and H(2)S level in the PVN in both sham-operated rats and
      CHF rats. CONCLUSIONS: Exogenous H(2)S in PVN increases RSNA, MAP and HR, and
      enhances CSAR. The effects are greater in CHF rats than those in sham-operated
      rats. Endogenous H(2)S in PVN is not responsible for the sympathetic activation
      and enhanced CSAR in CHF rats.

PMID- 23166828
TI  - Identification and characterization of bacterial vaginosis-associated pathogens
      using a comprehensive cervical-vaginal epithelial coculture assay.
AB  - Bacterial vaginosis (BV) is the most commonly treated female reproductive tract
      affliction, characterized by the displacement of healthy lactobacilli by an
      overgrowth of pathogenic bacteria. BV can contribute to pathogenic inflammation,
      preterm birth, and susceptibility to sexually transmitted infections. As the
      bacteria responsible for BV pathogenicity and their interactions with host
      immunity are not understood, we sought to evaluate the effects of BV-associated
      bacteria on reproductive epithelia. Here we have characterized the interaction
      between BV-associated bacteria and the female reproductive tract by measuring
      cytokine and defensin induction in three types of FRT epithelial cells following
      bacterial inoculation. Four BV-associated bacteria were evaluated alongside six
      lactobacilli for a comparative assessment. While responses differed between
      epithelial cell types, our model showed good agreement with clinical BV trends.
      We observed a distinct cytokine and human beta-defensin 2 response to BV
      associated bacteria, especially Atopobium vaginae, compared to most lactobacilli.
      One lactobacillus species, Lactobacillus vaginalis, induced an immune response
      similar to that elicited by BV-associated bacteria, stimulating significantly
      higher levels of cytokines and human beta-defensin 2 than other lactobacilli.
      These data provide an important prioritization of BV-associated bacteria and
      support further characterization of reproductive bacteria and their interactions
      with host epithelia. Additionally, they demonstrate the distinct immune response
      potentials of epithelial cells from different locations along the female
      reproductive tract.

PMID- 23166829
TI  - MEG network differences between low- and high-grade glioma related to epilepsy
      and cognition.
AB  - OBJECTIVE: To reveal possible differences in whole brain topology of epileptic
      glioma patients, being low-grade glioma (LGG) and high-grade glioma (HGG)
      patients. We studied functional networks in these patients and compared them to
      those in epilepsy patients with non-glial lesions (NGL) and healthy controls.
      Finally, we related network characteristics to seizure frequency and cognitive
      performance within patient groups. METHODS: We constructed functional networks
      from pre-surgical resting-state magnetoencephalography (MEG) recordings of 13 LGG
      patients, 12 HGG patients, 10 NGL patients, and 36 healthy controls. Normalized
      clustering coefficient and average shortest path length as well as modular
      structure and network synchronizability were computed for each group. Cognitive
      performance was assessed in a subset of 11 LGG and 10 HGG patients. RESULTS: LGG
      patients showed decreased network synchronizability and decreased global
      integration compared to healthy controls in the theta frequency range (4-8 Hz),
      similar to NGL patients. HGG patients' networks did not significantly differ from
      those in controls. Network characteristics correlated with clinical presentation
      regarding seizure frequency in LGG patients, and with poorer cognitive
      performance in both LGG and HGG glioma patients. CONCLUSION: Lesion histology
      partly determines differences in functional networks in glioma patients suffering
      from epilepsy. We suggest that differences between LGG and HGG patients' networks
      are explained by differences in plasticity, guided by the particular lesional
      growth pattern. Interestingly, decreased synchronizability and decreased global
      integration in the theta band seem to make LGG and NGL patients more prone to the
      occurrence of seizures and cognitive decline.

PMID- 23166831
TI  - Velocity of lordosis angle during spinal flexion and extension.
AB  - The importance of functional parameters for evaluating the severity of low back
      pain is gaining clinical recognition, with evidence suggesting that the angular
      velocity of lordosis is critical for identification of musculoskeletal deficits.
      However, there is a lack of data regarding the range of functional kinematics
      (RoKs), particularly which include the changing shape and curvature of the spine.
      We address this deficit by characterising the angular velocity of lordosis
      throughout the thoracolumbar spine according to age and gender. The velocity of
      lumbar back shape changes was measured using Epionics SPINE during maximum
      flexion and extension activities in 429 asymptomatic volunteers. The difference
      between maximum positive and negative velocities represented the RoKs. The mean
      RoKs for flexion decreased with age; 114 degrees /s (20-35 years), 100 degrees /s
      (36-50 years) and 83 degrees /s (51-75 years). For extension, the corresponding
      mean RoKs were 73 degrees /s, 57 degrees /s and 47 degrees /s. ANCOVA analyses
      revealed that age and gender had the largest influence on the RoKs (p<0.05). The
      Epionics SPINE system allows the rapid assessment of functional kinematics in the
      lumbar spine. The results of this study now serve as normative data for
      comparison to patients with spinal pathology or after surgical treatment.

PMID- 23166830
TI  - Early metabolic defects in dexamethasone-exposed and undernourished intrauterine
      growth restricted rats.
AB  - Poor fetal growth, also known as intrauterine growth restriction (IUGR), is a
      worldwide health concern. IUGR is commonly associated with both an increased risk
      in perinatal mortality and a higher prevalence of developing chronic metabolic
      diseases later in life. Obesity, type 2 diabetes or metabolic syndrome could
      result from noxious "metabolic programming." In order to better understand early
      alterations involved in metabolic programming, we modeled IUGR rat pups through
      either prenatal exposure to synthetic glucocorticoid (dams infused with
      dexamethasone 100 ug/kg/day, DEX) or prenatal undernutrition (dams feeding
      restricted to 30% of ad libitum intake, UN). Physiological (glucose and insulin
      tolerance), morphometric (automated tissue image analysis) and transcriptomic
      (quantitative PCR) approaches were combined during early life of these IUGR pups
      with a special focus on their endocrine pancreas and adipose tissue development.
      In the absence of catch-up growth before weaning, DEX and UN IUGR pups both
      presented basal hyperglycaemia, decreased glucose tolerance, and pancreatic islet
      atrophy. Other early metabolic defects were model-specific: DEX pups presented
      decreased insulin sensitivity whereas UN pups exhibited lowered glucose-induced
      insulin secretion and more marked alterations in gene expression of pancreatic
      islet and adipose tissue development regulators. In conclusion, these results
      show that before any catch-up growth, IUGR rats present early physiologic,
      morphologic and transcriptomic defects, which can be considered as initial
      mechanistic basis of metabolic programming.

PMID- 23166832
TI  - Comparing alternative methods for holding virgin honey bee queens for one week in
      mailing cages before mating.
AB  - In beekeeping, queen honey bees are often temporarily kept alive in cages. We
      determined the survival of newly-emerged virgin honey bee queens every day for
      seven days in an experiment that simultaneously investigated three factors: queen
      cage type (wooden three-hole or plastic), attendant workers (present or absent)
      and food type (sugar candy, honey, or both). Ten queens were tested in each of
      the 12 combinations. Queens were reared using standard beekeeping methods
      (Doolittle/grafting) and emerged from their cells into vials held in an incubator
      at 34C. All 12 combinations gave high survival (90 or 100%) for three days but
      only one method (wooden cage, with attendants, honey) gave 100% survival to day
      seven. Factors affecting queen survival were analysed. Across all combinations,
      attendant bees significantly increased survival (18% vs. 53%, p<0.001). In
      addition, there was an interaction between food type and cage type (p<0.001) with
      the honey and plastic cage combination giving reduced survival. An additional
      group of queens was reared and held for seven days using the best method, and
      then directly introduced using smoke into queenless nucleus colonies that had
      been dequeened five days previously. Acceptance was high (80%, 8/10) showing that
      this combination is also suitable for preparing queens for introduction into
      colonies. Having a simple method for keeping newly-emerged virgin queens alive in
      cages for one week and acceptable for introduction into queenless colonies will
      be useful in honey bee breeding. In particular, it facilitates the screening of
      many queens for genetic or phenotypic characteristics when only a small
      proportion meets the desired criteria. These can then be introduced into
      queenless hives for natural mating or insemination, both of which take place when
      queens are one week old.

PMID- 23166833
TI  - Micro-halocline enabled nutrient recycling may explain extreme Azolla event in
      the Eocene Arctic Ocean.
AB  - In order to understand the physicochemical mechanisms that could explain the
      massive growth of Azolla arctica in the Eocene Arctic Ocean, we carried out a
      laboratory experiment in which we studied the interacting effects of rain and
      wind on the development of salinity stratification, both in the presence and in
      the absence of a dense Azolla cover. Additionally, we carried out a mesocosm
      experiment to get a better understanding of the nutrient cycling within and
      beneath a dense Azolla cover in both freshwater and brackish water environments.
      Here we show that Azolla is able to create a windproof, small-scale salinity
      gradient in brackish waters, which allows for efficient recycling of nutrients.
      We suggest that this mechanism ensures the maintenance of a large standing
      biomass in which additional input of nutrients ultimately result in a further
      expansion of an Azolla cover. As such, it may not only explain the extent of the
      Azolla event during the Eocene, but also the absence of intact vegetative Azolla
      remains and the relatively low burial efficiency of organic carbon during this
      interval.

PMID- 23166834
TI  - Acetaminophen induces human neuroblastoma cell death through NFKB activation.
AB  - Neuroblastoma resistance to apoptosis may contribute to the aggressive behavior
      of this tumor. Therefore, it would be relevant to activate endogenous cellular
      death mechanisms as a way to improve neuroblastoma therapy. We used the
      neuroblastoma SH-SY5Y cell line as a model to study the mechanisms involved in
      acetaminophen (AAP)-mediated toxicity by measuring CYP2E1 enzymatic activity,
      NFkB p65 subunit activation and translocation to the nucleus, Bax accumulation
      into the mitochondria, cytochrome c release and caspase activation. AAP activates
      the intrinsic death pathway in the SH-SY5Y human neuroblastoma cell line. AAP
      metabolism is partially responsible for this activation, because blockade of the
      cytochrome CYP2E1 significantly reduced but did not totally prevent, AAP-induced
      SH-SY5Y cell death. AAP also induced NFkB p65 activation by phosphorylation and
      its translocation to the nucleus, where NFkB p65 increased IL-1beta production.
      This increase contributed to neuroblastoma cell death through a mechanism
      involving Bax accumulation into the mitochondria, cytochrome c release and
      caspase3 activation. Blockade of NFkB translocation to the nucleus by the peptide
      SN50 prevented AAP-mediated cell death and IL-1beta production. Moreover,
      overexpression of the antiapoptotic protein Bcl-x(L) did not decrease AAP
      mediated IL-1beta production, but prevented both AAP and IL-1beta-mediated cell
      death. We also confirmed the AAP toxic actions on SK-N-MC neuroepithelioma and
      U87MG glioblastoma cell lines. The results presented here suggest that AAP
      activates the intrinsic death pathway in neuroblastoma cells through a mechanism
      involving NFkB and IL-1beta.

PMID- 23166835
TI  - Identification of single-copy orthologous genes between Physalis and Solanum
      lycopersicum and analysis of genetic diversity in Physalis using molecular
      markers.
AB  - The genus Physalis includes a number of commercially important edible and
      ornamental species. Its high nutritional value and potential medicinal properties
      leads to the increased commercial interest in the products of this genus
      worldwide. However, lack of molecular markers prevents the detailed study of
      genetics and phylogeny in Physalis, which limits the progress of breeding. In the
      present study, we compared the DNA sequences between Physalis and tomato, and
      attempted to analyze genetic diversity in Physalis using tomato markers. Blasting
      23180 DNA sequences derived from Physalis against the International Tomato
      Annotation Group (ITAG) Release2.3 Predicted CDS (SL2.40) discovered 3356 single
      copy orthologous genes between them. A total of 38 accessions from at least six
      species of Physalis were subjected to genetic diversity analysis using 97 tomato
      markers and 25 SSR markers derived from P. peruviana. Majority (73.2%) of tomato
      markers could amplify DNA fragments from at least one accession of Physalis.
      Diversity in Physalis at molecular level was also detected. The average Nei's
      genetic distance between accessions was 0.3806 with a range of 0.2865 to 0.7091.
      These results indicated Physalis and tomato had similarity at both molecular
      marker and DNA sequence levels. Therefore, the molecular markers developed in
      tomato can be used in genetic study in Physalis.

PMID- 23166836
TI  - Variation in patterns of metal accumulation in thallus parts of Lessonia
      trabeculata (Laminariales; Phaeophyceae): implications for biomonitoring.
AB  - Seaweeds are well known to concentrate metals from seawater and have been
      employed as monitors of metal pollution in coastal waters and estuaries. However,
      research showing that various intrinsic and extrinsic factors can influence metal
      accumulation, raises doubts about the basis for using seaweeds in biomonitoring
      programmes. The thallus of brown seaweeds of the order Laminariales (kelps) is
      morphologically complex but there is limited information about the variation in
      metal accumulation between the different parts, which might result in erroneous
      conclusions being drawn if not accounted for in the biomonitoring protocol. To
      assess patterns of individual metals in the differentiated parts of the thallus
      (blade, stipe, holdfast), concentrations of a wide range of essential and non
      essential metals (Fe, Cr, Cu, Zn, Mn, Pb, Cd, Ni and Al) were measured in the
      kelp Lessonia trabeculata. Seaweeds were collected from three sampling stations
      located at 5, 30 and 60 m from an illegal sewage outfall close to Ventanas, Chile
      and from a pristine location at Faro Curaumilla. For the majority of metals the
      highest concentrations in bottom sediment and seaweed samples were found at the
      site closest to the outfall, with concentrations decreasing with distance from
      the outfall and at control stations; the exception was Cd, concentrations of
      which were higher at control stations. The patterns of metal concentrations in
      different thallus parts were metal specific and independent of sampling station.
      These results and the available literature suggest that biomonitoring of metals
      using seaweeds must take account of differences in the accumulation of metals in
      thallus parts of complex seaweeds.

PMID- 23166837
TI  - Analysis of the native structure, stability and aggregation of biotinylated human
      lysozyme.
AB  - Fibril formation by mutational variants of human lysozyme is associated with a
      fatal form of hereditary non-neuropathic systemic amyloidosis. Defining the
      mechanistic details of lysozyme aggregation is of crucial importance for
      understanding the origin and progression of this disease and related misfolding
      conditions. In this study, we show that a biotin moiety can be introduced site
      specifically at Lys33 of human lysozyme. We demonstrate, using biophysical
      techniques, that the structure and stability of the native-state of the protein
      are not detectably altered by this modification, and that the ability to form
      amyloid fibrils is unchanged. By taking advantage of biotin-avidin interactions,
      we show that super-resolution fluorescence microscopy can generate detailed
      images of the mature fibrils. This methodology can readily enable the
      introduction of additional probes into the protein, thereby providing the means
      through which to understand, in detail, the nature of the aggregation process of
      lysozyme and its variants under a variety of conditions.

PMID- 23166838
TI  - Antagonistic and cooperative actions of Kif7 and Sufu define graded intracellular
      Gli activities in Hedgehog signaling.
AB  - Graded Hedgehog (Hh) signaling governs the balance of Gli transcriptional
      activators and repressors to specify diverse ventral cell fates in the spinal
      cord. It remains unclear how distinct intracellular Gli activity is generated.
      Here, we demonstrate that Sufu acts universally as a negative regulator of Hh
      signaling, whereas Kif7 inhibits Gli activity in cooperation with, and
      independent of, Sufu. Together, they deter naive precursors from acquiring
      increasingly ventral identity. We show that Kif7 is also required to establish
      high intracellular Gli activity by antagonizing the Sufu-inhibition of Gli2.
      Strikingly, by abolishing the negative regulatory action of Sufu, diverse ventral
      cell fates can be specified in the absence of extracellular Hh signaling. These
      data suggest that Sufu is the primary regulator of graded Hh signaling and
      establish that the antagonistic and cooperative actions of Kif7 and Sufu are
      responsible for setting up distinct Gli activity in ventral cell fate
      specification.

PMID- 23166839
TI  - Fatp1 deficiency affects retinal light response and dark adaptation, and induces
      age-related alterations.
AB  - FATP1 is involved in lipid transport into cells and in intracellular lipid
      metabolism. We showed previously that this protein interacts with and inhibits
      the limiting-step isomerase of the visual cycle RPE65. Here, we aimed to analyze
      the effect of Fatp1-deficiency in vivo on the visual cycle, structure and
      function, and on retinal aging. Among the Fatp family members, we observed that
      only Fatp1 and 4 are expressed in the control retina, in both the neuroretina and
      the retinal pigment epithelium. In the neuroretina, Fatp1 is mostly expressed in
      photoreceptors. In young adult Fatp1(-/-) mice, Fatp4 expression was unchanged in
      retinal pigment epithelium and reduced two-fold in the neuroretina as compared to
      Fatp1(+/+) mice. The Fatp1(-/-) mice had a preserved retinal structure but a
      decreased electroretinogram response to light. These mice also displayed a
      delayed recovery of the b-wave amplitude after bleaching, however, visual cycle
      speed was unchanged, and both retinal pigment epithelium and photoreceptors
      presented the same fatty acid pattern compared to controls. In 2 year-old Fatp1(
      /-) mice, transmission electron microscopy studies showed specific abnormalities
      in the retinas comprising choroid vascularization anomalies and thickening of the
      Bruch membrane with material deposits, and sometimes local disorganization of the
      photoreceptor outer segments. These anomalies lead us to speculate that the
      absence of FATP1 accelerates the aging process.

PMID- 23166840
TI  - Sensitivity to lysosome-dependent cell death is directly regulated by lysosomal
      cholesterol content.
AB  - Alterations in lipid homeostasis are implicated in several neurodegenerative
      diseases, although the mechanisms responsible are poorly understood. We evaluated
      the impact of cholesterol accumulation, induced by U18666A, quinacrine or
      mutations in the cholesterol transporting Niemann-Pick disease type C1 (NPC1)
      protein, on lysosomal stability and sensitivity to lysosome-mediated cell death.
      We found that neurons with lysosomal cholesterol accumulation were protected from
      oxidative stress-induced apoptosis. In addition, human fibroblasts with
      cholesterol-loaded lysosomes showed higher lysosomal membrane stability than
      controls. Previous studies have shown that cholesterol accumulation is
      accompanied by the storage of lipids such as sphingomyelin, glycosphingolipids
      and sphingosine and an up regulation of lysosomal associated membrane protein-2
      (LAMP-2), which may also influence lysosomal stability. However, in this study
      the use of myriocin and LAMP deficient fibroblasts excluded these factors as
      responsible for the rescuing effect and instead suggested that primarily
      lysosomal cholesterol content determineD the cellular sensitivity to toxic
      insults. Further strengthening this concept, depletion of cholesterol using
      methyl-beta-cyclodextrin or 25-hydroxycholesterol decreased the stability of
      lysosomes and cells became more prone to undergo apoptosis. In conclusion,
      cholesterol content regulated lysosomal membrane permeabilization and thereby
      influenced cell death sensitivity. Our data suggests that lysosomal cholesterol
      modulation might be used as a therapeutic strategy for conditions associated with
      accelerated or repressed apoptosis.

PMID- 23166841
TI  - Modeling huddling penguins.
AB  - We present a systematic and quantitative model of huddling penguins. In this
      mathematical model, each individual penguin in the huddle seeks only to reduce
      its own heat loss. Consequently, penguins on the boundary of the huddle that are
      most exposed to the wind move downwind to more sheltered locations along the
      boundary. In contrast, penguins in the interior of the huddle neither have the
      space to move nor experience a significant heat loss, and they therefore remain
      stationary. Through these individual movements, the entire huddle experiences a
      robust cumulative effect that we identify, describe, and quantify. This
      mathematical model requires a calculation of the wind flowing around the huddle
      and of the resulting temperature distribution. Both of these must be recomputed
      each time an individual penguin moves since the huddle shape changes. Using our
      simulation results, we find that the key parameters affecting the huddle dynamics
      are the number of penguins in the huddle, the wind strength, and the amount of
      uncertainty in the movement of the penguins. Moreover, we find that the lone
      assumption of individual penguins minimizing their own heat loss results in all
      penguins having approximately equal access to the warmth of the huddle.

PMID- 23166842
TI  - ERK1/2 signaling plays an important role in topoisomerase II poison-induced G2/M
      checkpoint activation.
AB  - Topo II poisons, which target topoisomerase II (topo II) to generate enzyme
      mediated DNA damage, have been commonly used for anti-cancer treatment. While
      clinical evidence demonstrate a capability of topo II poisons in inducing
      apoptosis in cancer cells, accumulating evidence also show that topo II poison
      treatment frequently results in cell cycle arrest in cancer cells, which was
      associated with subsequent resistance to these treatments. Results in this report
      indicate that treatment of MCF-7 and T47D breast cancer cells with topo II
      poisons resulted in an increased phosphorylation of extracellular signal
      regulated kinase 1 and 2 (ERK1/2) and an subsequent induction of G2/M cell cycle
      arrest. Furthermore, inhibition of ERK1/2 activation using specific inhibitors
      markedly attenuated the topo II poison-induced G2/M arrest and diminished the
      topo II poison-induced activation of ATR and Chk1 kinases. Moreover, decreased
      expression of ATR by specific shRNA diminished topo II poison-induced G2/M arrest
      but had no effect on topo II poison-induced ERK1/2 activation. In contrast,
      inhibition of ERK1/2 signaling had little, if any, effect on topo II poison
      induced ATM activation. In addition, ATM inhibition by either incubation of cells
      with ATM specific inhibitor or transfection of cells with ATM specific siRNA did
      not block topo II poison-induced G2/M arrest. Ultimately, inhibition of ERK1/2
      signaling greatly enhanced topo II poison-induced apoptosis. These results
      implicate a critical role for ERK1/2 signaling in the activation of G2/M
      checkpoint response following topo II poison treatment, which protects cells from
      topo II poison-induced apoptosis.

PMID- 23166843
TI  - Differentiating psychopathy from general antisociality using the P3 as a
      psychophysiological correlate of attentional allocation.
AB  - Recent studies have shown that while psychopathy and non-psychopathic
      antisociality overlap, they differ in the extent to which cognitive impairments
      are present. Specifically, psychopathy has been related to abnormal allocation of
      attention, a function that is traditionally believed to be indexed by event
      related potentials (ERPs) of the P3-family. Previous research examining
      psychophysiological correlates of attention in psychopathic individuals has
      mainly focused on the parietally distributed P3b component to rare targets. In
      contrast, very little is known about the frontocentral P3a to infrequent novel
      events in psychopathy. Thus, findings on the P3 components in psychopathy are
      inconclusive, while results in non-psychopathic antisocial populations are
      clearer and point toward an inverse relationship between antisociality and P3
      amplitudes. The present study adds to extant literature on the P3a and P3b in
      psychopathy by investigating component amplitudes in psychopathic offenders (N =
      20), matched non-psychopathic offenders (N = 23) and healthy controls (N = 16).
      Also, it was assessed how well each offender group was able to differentially
      process rare novel and target events. The offender groups showed general
      amplitude reductions compared to healthy controls, but did not differ mutually on
      overall P3a/P3b amplitudes. However, the psychopathic group still exhibited
      normal neurophysiological differentiation when allocating attention to rare novel
      and target events, unlike the non-psychopathic sample. The results highlight
      differences between psychopathic and non-psychopathic offenders regarding the
      integrity of the neurocognitive processes driving attentional allocation, as well
      as the usefulness of alternative psychophysiological measures in differentiating
      psychopathy from general antisociality.

PMID- 23166844
TI  - Spontaneous abortion and a diet drug containing caffeine and ephedrine: a study
      within the Danish national birth cohort.
AB  - BACKGROUND: Medications may be consumed periconceptionally before a woman knows
      she is pregnant. In this study, the authors evaluate the association of a
      prescription diet drug (Letigen) containing ephedrine (20 mg) and caffeine (200
      mg) with spontaneous abortion (SAB) in the Danish National Birth Cohort. METHODS:
      Women were recruited during their first prenatal visit from 1996-2002. Pre
      conception and early pregnancy medication use was reported on the enrollment
      form, and pregnancy outcome was determined by linking the mother's Civil
      Registration Number to the Medical Birth Registry and the National Hospital
      Discharge Register. Of 97,903 eligible pregnancies, 4,443 ended in SAB between 5
      and 20 completed gestational weeks, inclusive. Letigen use was reported for 565
      pregnancies. Cox regression models accounting for left truncation were fit to
      estimate the effect of pre-conception and early pregnancy Letigen use on SAB.
      PRINCIPAL FINDINGS: The estimated maternal age-adjusted hazard ratio for SAB was
      1.1 (95% confidence interval 0.8-1.6) for any periconceptional Letigen use
      compared to no periconceptional use. CONCLUSIONS: Although Letigen has high
      levels of caffeine (the recommended 3 pills/day are approximately equivalent to
      caffeine from 6 cups of coffee), periconceptional use does not appear to be
      associated with an appreciably increased hazard of clinically recognized SAB.

PMID- 23166845
TI  - Open release of male mosquitoes infected with a wolbachia biopesticide: field
      performance and infection containment.
AB  - BACKGROUND: Lymphatic filariasis (LF) is a globally significant disease, with 1.3
      billion persons in 83 countries at risk. A coordinated effort of administering
      annual macrofilaricidal prophylactics to the entire at-risk population has
      succeeded in impacting and eliminating LF transmission in multiple regions.
      However, some areas in the South Pacific are predicted to persist as transmission
      sites, due in part to the biology of the mosquito vector, which has led to a call
      for additional tools to augment drug treatments. Autocidal strategies against
      mosquitoes are resurging in the effort against invasive mosquitoes and vector
      borne disease, with examples that include field trials of genetically modified
      mosquitoes and Wolbachia population replacement. However, critical questions must
      be addressed in anticipation of full field trials, including assessments of field
      competitiveness of transfected males and the risk of unintended population
      replacement. METHODOLOGY/PRINCIPAL FINDINGS: We report the outcome of field
      experiments testing a strategy that employs Wolbachia as a biopesticide. The
      strategy is based upon Wolbachia-induced conditional sterility, known as
      cytoplasmic incompatibility, and the repeated release of incompatible males to
      suppress a population. A criticism of the Wolbachia biopesticide approach is that
      unintended female release or horizontal Wolbachia transmission can result in
      population replacement instead of suppression. We present the outcome of
      laboratory and field experiments assessing the competitiveness of transfected
      males and their ability to transmit Wolbachia via horizontal transmission.
      CONCLUSIONS/SIGNIFICANCE: The results demonstrate that Wolbachia-transfected
      Aedes polynesiensis males are competitive under field conditions during a thirty
      week open release period, as indicated by mark, release, recapture and brood
      hatch failure among females at the release site. Experiments demonstrate the
      males to be 'dead end hosts' for Wolbachia and that methods were adequate to
      prevent population replacement at the field site. The findings encourage the
      continued development and extension of a Wolbachia autocidal approach to
      additional medically important mosquito species.

PMID- 23166846
TI  - Host life history strategy, species diversity, and habitat influence Trypanosoma
      cruzi vector infection in Changing landscapes.
AB  - BACKGROUND: Anthropogenic land use may influence transmission of multi-host
      vector-borne pathogens by changing diversity, relative abundance, and community
      composition of reservoir hosts. These reservoir hosts may have varying competence
      for vector-borne pathogens depending on species-specific characteristics, such as
      life history strategy. The objective of this study is to evaluate how
      anthropogenic land use change influences blood meal species composition and the
      effects of changing blood meal species composition on the parasite infection rate
      of the Chagas disease vector Rhodnius pallescens in Panama. METHODOLOGY/PRINCIPAL
      FINDINGS: R. pallescens vectors (N = 643) were collected in different habitat
      types across a gradient of anthropogenic disturbance. Blood meal species in DNA
      extracted from these vectors was identified in 243 (40.3%) vectors by
      amplification and sequencing of a vertebrate-specific fragment of the 12SrRNA
      gene, and T. cruzi vector infection was determined by pcr. Vector infection rate
      was significantly greater in deforested habitats as compared to contiguous
      forests. Forty-two different species of blood meal were identified in R.
      pallescens, and species composition of blood meals varied across habitat types.
      Mammals (88.3%) dominated R. pallescens blood meals. Xenarthrans (sloths and
      tamanduas) were the most frequently identified species in blood meals across all
      habitat types. A regression tree analysis indicated that blood meal species
      diversity, host life history strategy (measured as r(max), the maximum intrinsic
      rate of population increase), and habitat type (forest fragments and
      peridomiciliary sites) were important determinants of vector infection with T.
      cruzi. The mean intrinsic rate of increase and the skewness and variability of
      r(max) were positively associated with higher vector infection rate at a site.
      CONCLUSIONS/SIGNIFICANCE: In this study, anthropogenic landscape disturbance
      increased vector infection with T. cruzi, potentially by changing host community
      structure to favor hosts that are short-lived with high reproductive rates. Study
      results apply to potential environmental management strategies for Chagas
      disease.

PMID- 23166848
TI  - Direct interaction between EgFABP1, a fatty acid binding protein from
      Echinococcus granulosus, and phospholipid membranes.
AB  - BACKGROUND: Growth and maintenance of hydatid cysts produced by Echinococcus
      granulosus have a high requirement for host lipids for biosynthetic processes,
      membrane building and possibly cellular and developmental signalling. This
      requires a high degree of lipid trafficking facilitated by lipid transporter
      proteins. Members of the fatty acid binding protein (FABP) family have been
      identified in Echinococcus granulosus, one of which, EgFABP1 is expressed at the
      tegumental level in the protoscoleces, but it has also been described in both
      hydatid cyst fluid and secretions of protoscoleces. In spite of a considerable
      amount of structural and biophysical information on the FABPs in general, their
      specific functions remain mysterious. METHODOLOGY/PRINCIPAL FINDINGS: We have
      investigated the way in which EgFABP1 may interact with membranes using a variety
      of fluorescence-based techniques and artificial small unilamellar vesicles. We
      first found that bacterial recombinant EgFABP1 is loaded with fatty acids from
      the synthesising bacteria, and that fatty acid binding increases its resistance
      to proteinases, possibly due to subtle conformational changes induced on EgFABP1.
      By manipulating the composition of lipid vesicles and the ionic environment, we
      found that EgFABP1 interacts with membranes in a direct contact, collisional,
      manner to exchange ligand, involving both ionic and hydrophobic interactions.
      Moreover, we observed that the protein can compete with cytochrome c for
      association with the surface of small unilamellar vesicles (SUVs).
      CONCLUSIONS/SIGNIFICANCE: This work constitutes a first approach to the
      understanding of protein-membrane interactions of EgFABP1. The results suggest
      that this protein may be actively involved in the exchange and transport of fatty
      acids between different membranes and cellular compartments within the parasite.

PMID- 23166847
TI  - A novel procedure for precise quantification of Schistosoma japonicum eggs in
      bovine feces.
AB  - Schistosomiasis japonica is a zoonosis with a number of mammalian species acting
      as reservoir hosts, including water buffaloes which can contribute up to 75% to
      human transmission in the People's Republic of China. Determining prevalence and
      intensity of Schistosoma japonicum in mammalian hosts is important for
      calculating transmission rates and determining environmental contamination. A new
      procedure, the formalin-ethyl acetate sedimentation-digestion (FEA-SD) technique,
      for increased visualization of S. japonicum eggs in bovine feces, is described
      that is an effective technique for identifying and quantifying S. japonicum eggs
      in fecal samples from naturally infected Chinese water buffaloes and from carabao
      (water buffalo) in the Philippines. The procedure involves filtration,
      sedimentation, potassium hydroxide digestion and centrifugation steps prior to
      microscopy. Bulk debris, including the dense cellulosic material present in
      bovine feces, often obscures schistosome eggs with the result that prevalence and
      infection intensity based on direct visualization cannot be made accurately. This
      technique removes nearly 70% of debris from the fecal samples and renders the
      remaining debris translucent. It allows improved microscopic visualization of S.
      japonicum eggs and provides an accurate quantitative method for the estimation of
      infection in bovines and other ruminant reservoir hosts. We show that the FEA-SD
      technique could be of considerable value if applied as a surveillance tool for
      animal reservoirs of S. japonicum, particularly in areas with low to high
      infection intensity, or where, following control efforts, there is suspected
      elimination of schistosomiasis japonica.

PMID- 23166849
TI  - Affinity is an important determinant of the anti-trypanosome activity of
      nanobodies.
AB  - BACKGROUND: The discovery of Nanobodies (Nbs) with a direct toxic activity
      against African trypanosomes is a recent advancement towards a new strategy
      against these extracellular parasites. The anti-trypanosomal activity relies on
      perturbing the highly active recycling of the Variant-specific Surface
      Glycoprotein (VSG) that occurs in the parasite's flagellar pocket.
      METHODOLOGY/PRINCIPAL FINDINGS: Here we expand the existing panel of Nbs with
      anti-Trypanosoma brucei potential and identify four categories based on their
      epitope specificity. We modified the binding properties of previously identified
      Nanobodies Nb_An05 and Nb_An33 by site-directed mutagenesis in the paratope and
      found this to strongly affect trypanotoxicity despite retention of antigen
      targeting properties. Affinity measurements for all identified anti-trypanosomal
      Nbs reveal a strong correlation between trypanotoxicity and affinity (K(D)),
      suggesting that it is a crucial determinant for this activity. Half maximal
      effective (50%) affinity of 57 nM was calculated from the non-linear dose
      response curves. In line with these observations, Nb humanizing mutations only
      preserved the trypanotoxic activity if the K(D) remained unaffected.
      CONCLUSIONS/SIGNIFICANCE: This study reveals that the binding properties of
      Nanobodies need to be compatible with achieving an occupancy of >95% saturation
      of the parasite surface VSG in order to exert an anti-trypanosomal activity. As
      such, Nb-based approaches directed against the VSG target would require binding
      to an accessible, conserved epitope with high affinity.

PMID- 23166850
TI  - Projecting the long-term impact of school- or community-based mass-treatment
      interventions for control of Schistosoma infection.
AB  - BACKGROUND: Schistosomiasis remains a significant health burden in many areas of
      the world. Morbidity control, focused on limiting infection intensity through
      periodic delivery of anti-schistosomal medicines, is the thrust of current World
      Health Organization guidelines (2006) for reduction of Schistosoma-related
      disease. A new appreciation of the lifetime impact of repeated Schistosoma
      infection has directed attention toward strategies for greater suppression of
      parasite infection per se, with the goal of transmission interruption. Variations
      in drug schedules involving increased population coverage and/or treatment
      frequency are now undergoing field trials. However, their relative effectiveness
      in long-term infection suppression is presently unknown. METHODOLOGY/PRINCIPAL
      FINDINGS: Our study used available field data to calibrate advanced network
      models of village-level Schistosoma transmission to project outcomes of six
      different community- or school age-based programs, as compared to the impact of
      current 2006 W.H.O. recommended control strategies. We then scored the number of
      years each of 10 typical villages would remain below 10% infection prevalence (a
      practicable level associated with minimal prevalence of disease). All strategies
      that included four annual treatments effectively reduced community prevalence to
      less than 10%, while programs having yearly gaps ('holidays') failed to reach
      this objective in half of the communities. Effective post-program suppression of
      infection prevalence persisted in half of the 10 villages for 7-10 years, whereas
      in five high-risk villages, program effects on prevalence lasted zero to four
      years only. CONCLUSIONS/SIGNIFICANCE: At typical levels of treatment adherence
      (60 to 70%), current WHO recommendations will likely not achieve effective
      suppression of Schistosoma prevalence unless implemented for >=6 years. Following
      more aggressive 4 year annual intervention, some communities may be able to
      continue without further intervention for 8-10 years, while in higher-risk
      communities, annual treatment may prove necessary until eco-social factors
      fostering transmission are removed. Effective ongoing surveillance and locally
      targeted annual intervention must then become their mainstays of control.

PMID- 23166851
TI  - Development of a temperature-switch PCR-based SNP typing method for Mycobacterium
      ulcerans.
AB  - Mycobacterium ulcerans (M. ulcerans), the causative agent of the devastating skin
      disease Buruli ulcer (BU), is characterized by an extremely low level of genetic
      diversity. Recently, we have reported the first discrimination of closely related
      M. ulcerans variants in the BU endemic Densu River Valley of Ghana. In the study
      real-time PCR-based single nucleotide polymorphism (SNP) typing at 89 predefined
      loci revealed the presence of ten M. ulcerans haplotypes circulating in the BU
      endemic region. Here we describe the development of temperature-switch PCR (TSP)
      assays that allow distinguishing these haplotypes by conventional agarose gel
      based analysis of the PCR products. After validation of the accuracy of typing
      results, the TSP assays were successfully established in a reference laboratory
      in Ghana. Development of the cost-effective and rapid TSP-based genetic
      fingerprinting method will thus allow investigating the spread of M. ulcerans
      clones by regular genetic monitoring in BU endemic countries.

PMID- 23166852
TI  - First attempt to validate human IgG antibody response to Nterm-34kDa salivary
      peptide as biomarker for evaluating exposure to Aedes aegypti bites.
AB  - BACKGROUND: Much effort is being devoted for developing new indicators to
      evaluate the human exposure to Aedes mosquito bites and the risk of arbovirus
      transmission. Human antibody (Ab) responses to mosquito salivary components could
      represent a promising tool for evaluating the human-vector contact.
      METHODOLOGY/PRINCIPAL FINDINGS: To develop a specific biomarker of human exposure
      to Aedes aegypti bites, we measured IgG Ab response to Ae. aegypti Nterm-34 kDa
      salivary peptide in exposed children in 7 villages of Southern Benin (West
      Africa). Results showed that specific IgG response presented high inter
      individual heterogeneity between villages. IgG response was associated with
      rainfall and IgG level increased from dry (low exposure) to rainy (high exposure)
      seasons. These findings indicate that IgG Ab to Nterm-34 kDa salivary peptide may
      represent a reliable biomarker to detect variation in human exposure to Ae.
      aegypti bites. CONCLUSION/SIGNIFICANCE: This preliminary study highlights the
      potential use of Ab response to this salivary peptide for evaluating human
      exposure to Ae. aegypti. This biomarker could represent a new promising tool for
      assessing the risk of arbovirus transmission and for evaluating the efficacy of
      vector control interventions.

PMID- 23166853
TI  - Population genetic structuring in Opisthorchis viverrini over various spatial
      scales in Thailand and Lao PDR.
AB  - Khon Kaen Province in northeast Thailand is known as a hot spot for
      opisthorchiasis in Southeast Asia. Preliminary allozyme and mitochondrial DNA
      haplotype data from within one endemic district in this Province (Ban Phai),
      indicated substantial genetic variability within Opisthorchis viverrini. Here, we
      used microsatellite DNA analyses to examine the genetic diversity and population
      structure of O. viverrini from four geographically close localities in Khon Kaen
      Province. Genotyping based on 12 microsatellite loci yielded a mean number of
      alleles per locus that ranged from 2.83 to 3.7 with an expected heterozygosity in
      Hardy-Weinberg equilibrium of 0.44-0.56. Assessment of population structure by
      pairwise F(ST) analysis showed inter-population differentiation (P<0.05) which
      indicates population substructuring between these localities. Unique alleles were
      found in three of four localities with the highest number observed per locality
      being three. Our results highlight the existence of genetic diversity and
      population substructuring in O. viverrini over a small spatial scale which is
      similar to that found at a larger scale. This provides the basis for the
      investigation of the role of parasite genetic diversity and differentiation in
      transmission dynamics and control of O. viverrini.

PMID- 23166854
TI  - Transcriptional analysis of a unique set of genes involved in Schistosoma mansoni
      female reproductive biology.
AB  - Schistosomiasis affects more than 200 million people globally. The pathology of
      schistosome infections is due to chronic tissue inflammation and damage from
      immune generated granulomas surrounding parasite eggs trapped in host tissues.
      Schistosoma species are unique among trematode parasites because they are
      dioecious; females require paring with male parasites in order to attain
      reproductive maturity and produce viable eggs. Ex vivo cultured females lose the
      ability to produce viable eggs due to an involution of the vitellarium and loss
      of mature oocytes. In order to better understand schistosome reproductive biology
      we used data generated by serial analysis of gene expression (SAGE) to identify
      uncharacterized genes which have different transcript abundance in mature
      females, those that have been paired with males, and immature females obtained
      from unisexual infections. To characterize these genes we used bioinformatics,
      transcript localization, and transcriptional analysis during the regression of in
      vitro cultured females. Genes transcribed exclusively in mature females localize
      primarily in the vitellocytes and/or the ovary. Genes transcribed exclusively in
      females from single sex infections localize to vitellocytes and subtegumental
      cells. As female reproductive tissues regress, eggshell precursor proteins and
      genes involved in eggshell synthesis largely have decreased transcript abundance.
      However, some genes with elevated transcript abundance in mature adults have
      increased gene expression following regression indicating that the genes in this
      study function both in eggshell biology as well as vitellogenesis and maintenance
      of female reproductive tissues. In addition, we found that genes enriched in
      females from single sex infections have increased expression during regression in
      ex vivo females. By using these transcriptional analyses we can direct research
      to examine the areas of female biology that are both relevant to understanding
      the overall process of female development and worm pairing while determining
      novel therapeutic approaches directed at the maturation of female schistosomes.

PMID- 23166855
TI  - Salmonella typhi in the democratic republic of the congo: fluoroquinolone
      decreased susceptibility on the rise.
AB  - BACKGROUND: Drug resistance of Salmonella enterica serovar Typhi (Salmonella
      Typhi) to first-line antibiotics is emerging in Central Africa. Although
      increased use of fluoroquinolones is associated with spread of resistance,
      Salmonella Typhi with decreased ciprofloxacin susceptibility (DCS) has rarely
      been reported in Central Africa. METHODOLOGY/PRINCIPAL FINDINGS: As part of a
      microbiological surveillance study in the Democratic Republic of the Congo (DR
      Congo), Salmonella Typhi isolates from bloodstream infections were collected
      prospectively between 2007 and 2011. The genetic relationship of the Salmonella
      Typhi isolates was assessed by pulsed-field gel electrophoresis (PFGE). The
      antimicrobial resistance profile of the isolates was determined and mutations
      associated with DCS were studied. In total, 201 Salmonella Typhi isolates were
      collected. More than half of the Salmonella Typhi isolates originated from
      children and young adults aged 5-19. Thirty different PFGE profiles were
      identified, with 72% of the isolates showing a single profile. Multidrug
      resistance, DCS and azithromycin resistance were 30.3%, 15.4% and 1.0%,
      respectively. DCS was associated with point mutations in the gyrA gene at codons
      83 and 87. CONCLUSIONS/SIGNIFICANCE: Our study describes the first report of
      widespread multidrug resistance and DCS among Salmonella Typhi isolates from DR
      Congo. Our findings highlight the need for increased microbiological diagnosis
      and surveillance in DR Congo, being a prerequisite for rational use of
      antimicrobials and the development of standard treatment guidelines.

PMID- 23166856
TI  - We need to know ... now!

PMID- 23166857
TI  - TMV-Gate vectors: gateway compatible tobacco mosaic virus based expression
      vectors for functional analysis of proteins.
AB  - Plant viral expression vectors are advantageous for high-throughput functional
      characterization studies of genes due to their capability for rapid, high-level
      transient expression of proteins. We have constructed a series of tobacco mosaic
      virus (TMV) based vectors that are compatible with Gateway technology to enable
      rapid assembly of expression constructs and exploitation of ORFeome collections.
      In addition to the potential of producing recombinant protein at grams per
      kilogram FW of leaf tissue, these vectors facilitate either N- or C-terminal
      fusions to a broad series of epitope tag(s) and fluorescent proteins. We
      demonstrate the utility of these vectors in affinity purification,
      immunodetection and subcellular localisation studies. We also apply the vectors
      to characterize protein-protein interactions and demonstrate their utility in
      screening plant pathogen effectors. Given its broad utility in defining protein
      properties, this vector series will serve as a useful resource to expedite gene
      characterization efforts.

PMID- 23166859
TI  - Constitutive law and flow mechanism in diamond deformation.
AB  - Constitutive laws and crystal plasticity in diamond deformation have been the
      subjects of substantial interest since synthetic diamond was made in 1950's. To
      date, however, little is known quantitatively regarding its brittle-ductile
      properties and yield strength at high temperatures. Here we report, for the first
      time, the strain-stress constitutive relations and experimental demonstration of
      deformation mechanisms under confined high pressure. The deformation at room
      temperature is essentially brittle, cataclastic, and mostly accommodated by
      fracturing on {111} plane with no plastic yielding at uniaxial strains up to 15%.
      At elevated temperatures of 1000 degrees C and 1200 degrees C diamond crystals
      exhibit significant ductile flow with corresponding yield strength of 7.9 and 6.3
      GPa, indicating that diamond starts to weaken when temperature is over 1000
      degrees C. At high temperature the plastic deformation and ductile flow is
      meditated by the <110>{111} dislocation glide and a very active {111} micro
      twinning.

PMID- 23166858
TI  - Hierarchical modularity in ERalpha transcriptional network is associated with
      distinct functions and implicates clinical outcomes.
AB  - Recent genome-wide profiling reveals highly complex regulation networks among
      ERalpha and its targets. We integrated estrogen (E2)-stimulated time-series
      ERalpha ChIP-seq and gene expression data to identify the ERalpha-centered
      transcription factor (TF) hubs and their target genes, and inferred the time
      variant hierarchical network structures using a Bayesian multivariate modeling
      approach. With its recurrent motif patterns, we determined three embedded
      regulatory modules from the ERalpha core transcriptional network. The GO analyses
      revealed the distinct biological function associated with each of three embedded
      modules. The survival analysis showed the genes in each module were able to
      render a significant survival correlation in breast cancer patient cohorts. In
      summary, our Bayesian statistical modeling and modularity analysis not only
      reveals the dynamic properties of the ERalpha-centered regulatory network and
      associated distinct biological functions, but also provides a reliable and
      effective genomic analytical approach for the analysis of dynamic regulatory
      network for any given TF.

PMID- 23166860
TI  - Enhancing electrochemical detection on graphene oxide-CNT nanostructured
      electrodes using magneto-nanobioprobes.
AB  - Graphene and related materials have come to the forefront of research in
      electrochemical sensors during recent years due to the promising properties of
      these nanomaterials. Further applications of these nanomaterials have been
      hampered by insufficient sensitivity offered by these nanohybrids for the type of
      molecules requiring lower detection ranges. Here, we report a signal
      amplification strategy based on magneto-electrochemical immunoassay which
      combines the advantages of carbon nanotube and reduced graphene oxide together
      with electrochemical bursting of magnetic nanoparticles into a large number of
      metal ions. Sensitive detection was achieved by precisely designing the
      nanohybrid and correlating the available metal ions with analyte concentration.
      We confirmed the ultrahigh sensitivity of this method for a new generation
      herbicide diuron and its analogues up to sub-picomolar concentration in standard
      water samples. The novel immune-detection platform showed the excellent potential
      applicability in rapid and sensitive screening of environmental pollutants or
      toxins in samples.

PMID- 23166861
TI  - Physically Abused Women's Experiences of Sexual Victimization and their
      Children's Disruptive Behavior Problems.
AB  - OBJECTIVE: Despite the substantial co-occurrence of women's experiences of
      physical and sexual violence, very little is known about their separate and
      combined effects on child functioning. The present study examines whether sexual
      victimization experienced by physically abused women is associated with their
      children's disruptive behavior problems, after controlling for mothers' physical
      victimization and parent to child aggression. It also tests the hypothesis that
      maternal distress mediates the association between women's sexual victimization
      and their children's disruptive behavior problems.  METHOD: The sample includes
      449 mothers and their children (4-8 years) who were recruited while residing in
      domestic violence shelters. Mothers reported on their experiences of physical and
      sexual victimization over the past year and their current symptoms of
      psychological distress. Trained diagnosticians interviewed mothers about their
      children's disruptive behavior problems.  RESULTS: Approximately 75% of the women
      reported experiences of sexual victimization. Physically abused women's
      experiences of sexual victimization correlated positively with their children's
      disruptive behavior problems and their own psychological distress. The results of
      path analyses indicated that maternal psychological distress mediates the
      relation between women's experiences of sexual victimization and their children's
      disruptive behavior problems.  CONCLUSIONS: This research suggests that
      physically abused women's experiences of sexual victimization are important for
      understanding their children's disruptive behavior problems. Additionally, this
      research provides further evidence that maternal psychological distress is
      important for understanding how intimate partner violence might influence
      children.

PMID- 23166862
TI  - The expression and distribution of alpha-Gal gene in various species ocular
      surface tissue.
AB  - AIM: To examine the alpha-Gal gene expression and distribution in the different
      species/genus and developing phase animal ocular surface tissue. METHODS: alpha
      Gal binding assay were carried out on various animal eye sections. Photograph,
      slit-lamp observation on various eye showed normal corneal transparence. RESULTS:
      A strong alpha-Gal expression in invertebrates and some vertebrates ocular
      tissue, but no alpha-Gal binding in birds, fish and mammal. alpha-Gal expression
      change in the development of mice ocular surface tissue (except sclera) and
      display genus dependency in the different murine ocular surface tissue.
      CONCLUSION: This study identified specific alpha-Gal epitopes binding area in the
      ocular surface of several species and may solve the problem that naive ocular
      surface may be used as natural alpha-Gal gene knockout model/high risk
      immunologic rejection model or ocular surface scaffold material.

PMID- 23166863
TI  - Effects of preservation time on proliferative potential of human limbal
      stem/progenitor cells.
AB  - AIM: To determine the proliferative potential and the maintenance of stem cell
      activity in stored human limbal tissues, and correlate this with the preservation
      time, cell viability and the expression of stem cell markers. METHODS: Thirty
      limbal rims were split into 4 parts and stored in corneal preservation medium at
      4 degrees C for 0, 1, 4, or 7 days. The limbal stem cell and mitotic markers P63,
      CK19, proliferating cell nuclear antigen (PCNA), and Ki67 were determined by
      immunohistochemical staining. The proliferative potential of limbal epithelial
      cells was assessed by cell viability, the ability of generating stratified
      epithelium, and colony forming assay. RESULTS: The stored tissues maintained
      limbal stratified structure to 7 days and exhibited comparable expression level
      of stem cell and mitotic markers. The proportion of viable cells decreased with
      the prolonged preservation time, while colony forming efficiency decreased from
      the 1(st) day and disappeared at the 4(th) day. When inoculated on amniotic
      membrane, the cells preserved for 1 day formed a stratified epithelium, while the
      cells from 4 days' preservation formed a discontinuous layer. CONCLUSION: The
      colony forming efficiency of limbal epithelial stem/progenitor cells decreased
      rapidly with the increasing preservation time, while the expression level of
      markers and capacity of forming epithelial monolayer on amniotic membrane
      decreased gradually. The limbal epithelial stem cells lost their function earlier
      than the lost expression level of stem cell markers. This may help us to better
      choose the appropriate preservation grafts for future limbal stem cell
      transplantation.

PMID- 23166864
TI  - Homemade lyophilized cross linking amniotic sustained-release drug membrane with
      anti-scarring role after filtering surgery in rabbit eyes.
AB  - AIM: To investigate the antifibrotic effect of the freeze-dried bilayered fibrin
      binding amniotic membrane as a drug delivery system on glaucoma surgery in rabbit
      model. The aim of this study was to prepare a novel local delivery system for the
      sustained and controllable release of 5-Fu. METHODS: Twenty-four Japanese white
      rabbits were randomized into three groups: the experimental group (ocular
      trabeculectomy in combination with 5-Fu loaded freeze-dried bilayered fibrin
      binding amniotic membrane transplantation), the control group (ocular
      trabeculectomy in combination with 5-Fu) and the blank group (single
      trabeculectomy). HE staining, massion staining and immunohistochemistry for alpha
      SMA were performed on days 7, 14, 21 and 30 following surgery. The concentration
      of 5-Fu in rabbit aqueous humor was examined by high performance liquid
      chromatography (HPLC) 3 days after the surgery. RESULTS: Statistical differences
      were noted in intraocular pressure among groups on day 7, 14, 21 and 30 following
      surgery. Histology further demonstrated that trabeculectomy in combination with
      freeze-dried bilayered fibrin-binding amniotic membrane yielded well wound
      healing and no scar formation and was beneficial for long term effect.
      CONCLUSION: HPLC showed a good slow-release effect with freeze-dried bilayered
      fibrin-binding amniotic membrane.

PMID- 23166865
TI  - Adenoviral 15-lipoxygenase-1 gene transfer inhibits hypoxia-induced proliferation
      of retinal microvascular endothelial cells in vitro.
AB  - AIM: To investigate whether 15-Lipoxygenase-1 (15-LOX-1) plays an important role
      in the regulation of angiogenesis, inhibiting hypoxia-induced proliferation of
      retinal microvascular endothelial cells (RMVECs) and the underlying mechanism.
      METHODS: Primary RMVECs were isolated from the retinas of C57/BL6J mice and
      identified by an evaluation for FITC-marked CD31. The hypoxia models were
      established with the Bio-bag and evaluated with a blood-gas analyzer. Experiments
      were performed using RMVECs treated with and without transfer Ad-15-LOX-1 or Ad
      vector both under hypoxia and normoxia condition at 12, 24, 48, 72 hours. The
      efficacy of the gene transfer was assessed by immunofluorescence staining. Cells
      proliferation was evaluated by the CCK-8 method. RNA and protein expressions of
      15-LOX-1, VEGF-A, VEGFR-2, eNOs and PPAR-r were analyzed by real-time reverse
      transcription polymerase chain reaction (RT-PCR) and Western blot. RESULTS:
      Routine evaluation for FITC-marked CD31 showed that cells were pure. The results
      of blood-gas analysis showed that when the cultures were exposed to hypoxia for
      more than 2 hours, the Po2 was 4.5 to 5.4 Kpa. We verified RMVECs could be
      infected with Ad-15-LOX-1 or Ad-vector via Fluorescence microscopy. CCK-8
      analysis revealed that the proliferative capacities of RMVECs in hypoxic group
      were significantly higher at each time point than they were in normoxic group
      (P<0.05). In a hypoxic condition, the proliferative capacities of RMVECs in 15
      LOX-1 group were significantly inhibited (P<0.05). Real-time RT-PCR analysis
      revealed that the expressions of VEGF-A, VEGF-R2 and eNOs mRNA increased in
      hypoxia group compared with normoxia group (P<0.01). However, the expressions of
      15-LOX-1, PPAR-r mRNA decreased in hypoxia group compared with normoxia group
      (P<0.01). It also showed that in a hypoxic condition, the expressions of VEGF-A,
      VEGF-R2 and eNOs mRNA decreased significantly in 15-LOX-1 group compared with
      hypoxia group (P<0.01). However, 15-LOX-1 and PPAR-r mRNA increased significantly
      in 15-LOX-1 group compared with hypoxia group (P<0.01). There was no significant
      difference of the mRNA expressions between vector group and hypoxia group
      (P>0.05). Western blot analysis revealed that the expressions of relative
      proteins were also ranked in that order. CONCLUSION: Our results suggested that
      15-LOX-1 and PPAR-r might act as a negative regulator of retinal angiogenesis.
      And the effect of 15-LOX-1 overexpression is an anti-angiogenic factor in hypoxia
      induced retinal neovascularization (RNV). Overexpression 15-LOX-1 on RMVECs of
      hypoxia-induced RNV blocked signaling cascades by inhibiting hypoxia-induced
      increases in VEGF family. PPAR-r effect on VEGFR(2) could be an additional
      mechanism whereby 15-LOX-1 inhibited the hypoxia-induced RNV.

PMID- 23166866
TI  - Regulation of Eaf2 in mouse lens cells apoptosis induced by ultraviolet
      radiation.
AB  - AIM: To investigate the regulation of Eaf2 protein in mouse lens cells apoptosis
      induced by ultraviolet (UV) radiation. METHODS: An eye of Eaf2 gene knockout mice
      or normal control mice was exposed to UV radiation, and the other one was non
      exposed. All of lenses were analyzed by TUNEL and caspase 3 activity assays to
      determine the difference of the apoptosis induced by UV radiation. In addition,
      exposed and non-exposed lenses were analyzed by quantified p53 expression and
      real-time reverse transcription-polymerase chain reaction (RT-PCR) of Bax, Bid,
      Apaf-1, Puma and Noxa, to compare Eaf2 gene knockout mice and normal control
      mice. RESULTS: UV radiation caused apoptosis of lens cells in normal control mice
      and Eaf2 knockout mice. Activity of caspase 3 was significantly higher in normal
      control mice than Eaf2 knockout mice. Expression of p53 protein was significantly
      higher in lenses exposed to UV radiation than nonexposed lenses, but was similar
      between Eaf2 gene knockout mice and normal control mice in the same UV condition.
      After exposing to UV radiation, the analysis of real-time RT-PCR demonstrated
      that mRNA levels of Puma and Noxa were significantly higher in lenses of normal
      control mice than Eaf2 gene knockout mice, and that mRNA levels of Bax, Bid and
      Apaf-1 were not significantly different between gene knockout mice and normal
      control mice. CONCLUSION: Eaf2 increases lens cells apoptosis induced by
      ultraviolet radiation. And Eaf2 up-regulates expression of the Puma and the Noxa
      to act on lens cells apoptosis after UV radiation.

PMID- 23166867
TI  - Interference of Y-27632 on the signal transduction of transforming growth factor
      beta type 1 in ocular Tenon capsule fibroblasts.
AB  - AIM: To investigate the interfering effect of Y-27632, a ROCK-I selective
      inhibitor, on the signal transduction pathway of transforming growth factor-beta1
      (TGF-beta1) in ocular Tenon capsule fibroblasts (OTFS) in vitro. METHODS: After
      OTFS from passages 4 to 6 in vitro were induced by TGF-beta1 and then treated by
      Y-27632, the changes of the OTFS cell cycles were analyzed via flow cytometry,
      and the proteins expression of the alpha-smooth muscular actin (alpha-SMA),
      connective tissue growth factor (CTGF), collagen I were calculated by Western
      blot. After OTFS treated by the different concentrations of Y-27632, the
      expression levels of the alpha-SMA, CTGF and collagen I mRNA were assayed by RT
      PCR. RESULTS: Y-27632 had no markedly effect on the OTFS cell cycles. After
      treated by TGF-beta1, OTFS in G1 period significantly increased. The cell cycles
      distribution by both TGF-beta1 and Y-27632 had no remarkable difference from that
      in control group. Y-27632 significantly inhibited the proteins expressions of
      both alpha-SMA and CTGF, while to some extent inhibited that of collagen I. TGF
      beta1 significantly promoted the proteins expressions of alpha-SMA, CTGF and
      collagen I. After OTFS treated by both TGF-beta1 and Y-27632, of alpha-SMA, the
      protein expression was similar with that in control group (P=0.066>0.05), but the
      protein expression of CTGF or collagen I, respectively, was significantly
      different from that in control group (P=0.000<0.01). The differences of
      expressions of the alpha-SMA, CTGF and collagen I mRNA in 30, 150, 750umol/L Y
      27632 group were statistically significant, compared with those in control group,
      respectively (alpha-SMA, P=0.002, 0.000, 0.000; CTGF, P=0.014, 0.002, 0.001;
      collagen I, P=0.003, 0.002, 0.000). CONCLUSION: Blocking the Rho/ROCK signaling
      pathway by using of Y-27632 could inhibit the cellular proliferation and the
      expression of both CTGF and alpha-SMA whatever OTFS induced by TGF-beta1 or not.
      Y-27632 suppressed the expression of collagen I mRNA without induction.

PMID- 23166868
TI  - Evaluation of the new OxyPlateTM Anaerobic System for the isolation of ocular
      anaerobic bacteria.
AB  - AIM: Anaerobic bacteria can cause ocular infections. We tested the OxyPlateTM
      Anaerobic System (OXY) to isolate pertinent anaerobic bacteria that can cause
      ocular disease. METHODS: OXY, which does not require direct anaerobic conditions
      (i.e. bags, jars), was compared to conventional isolation of incubating culture
      media in anaerobic bags. Standard colonies counts were performed on anaerobic
      ocular bacterial isolates under aerobic and anaerobic conditions (anaerobic bags)
      using agar media: 1) OXY (aerobic only), 2) 5% sheep blood (SB), 3) Chocolate,
      and 4) Schaedler. The bacteria tested were de-identified ocular isolates cultured
      from endophthalmitis and dacryocystitis that include 10 Propionibacterium acnes
      and 3 Actinomyces species. The colony counts for each bacteria isolate, on each
      culturing condition, were ranked from largest to smallest, and non-parametrically
      compared to determine the best culturing condition. RESULTS: All anaerobic
      conditions were positive for all of the anaerobic isolates. SB and Schaedler's
      agar under aerobic conditions did not support the growth of anaerobic bacteria.
      Sparse growth was noted on chocolate agar with Propionibacterium acnes. As an
      anaerobic system, SB in an anaerobic bag isolated higher colony counts than OXY
      (P=0.0028) and chocolate agar (P=0.0028). CONCLUSION: Although OXY did not test
      to be more efficient than other anaerobic systems, it appears to be a reasonable
      alternative for isolating anaerobic bacteria from ocular sites. The use of an
      agar medium in a specially designed plate, without the requirement of an
      anaerobic bag, rendered OXY as an advantage over other anaerobic systems.

PMID- 23166869
TI  - Ferrara ring segments implantation for treating keratoconus.
AB  - AIM: To investigate the efficacy of Ferrara rings (FR) implantation in the
      treatment of keratoconus. METHODS: It was a retrospective case series descriptive
      study. The sample was comprised of 50 patients 79 eyes diagnosed with progressive
      keratoconus. This included 24 (48%) males and 26 (52%) females between the age of
      13 and 44 years. All participants underwent surgical implantation of FR in the
      period between January 2009 and September 2010 at Jordan University Hospital.
      Thorough ophthalmologic examinations were applied to measure vital variables for
      each pathological condition before and after surgery. RESULTS: Findings indicated
      an overall significant postoperative improvement in both uncorrected visual
      acuity (UCVA) and best spectacle corrected visual acuity (BSCVA) throughout
      follow up visits. Moreover, results illustrated a significant decrease in
      spherical equivalent (SE) and keratometric readings (lower, higher and the
      average). CONCLUSION: Surgical intervention strategies are being frequently
      developed to meet the needs of patients with keratoconus. The implantation of
      Ferrara rings has proven to be a safe and feasible alternative procedure for the
      treatment of mild-moderate keratoconus especially for patients with contact
      lenses intolerance. We have found that this procedure has improved visual
      outcomes in all eyes studied. Nevertheless, further research is needed to
      investigate long term outcomes.

PMID- 23166870
TI  - Non-buckled vitrectomy for retinal detachment with inferior breaks and
      proliferative vitreoretinophathy.
AB  - AIM: To investigate the efficacy of non-buckled vitrectomy with classical
      endotamponade agents in the treatment of primary retinal detachment (RD)
      complicated by inferior breaks and proliferative vitreoretinophathy (PVR).
      METHODS: A retrospective, consecutive and case series study of 40 patients with
      inferior break RD and PVR >=C1 was conducted. All patients underwent a standard 3
      port 20-gauge pars plana vitrectomy (PPV) with gas or silicone oil tamponade
      without supplementary scleral buckling. The vitreous and all proliferative
      membrane were completely removed, and retinectomy was performed when necessary.
      The mean follow-up was 12.5 months. The primary and final anatomic success rate,
      visual acuity and complications were recorded and analyzed. RESULTS: Primary
      anatomic success rate was achieved in 35 of 40 eyes (87.5%) and the final
      anatomic success rate was 100%. The most common cause of redetachment was
      recurrent PVR. The best-corrected visual acuity (BCVA) at final follow-up was
      improved in 34 eyes (85%), remained stable in 1 eye (2.5%), and worsened in 5
      eyes (12.5%). The mean visual acuity at final follow-up was improved
      significantly (P=0.000). CONCLUSION: This retrospective study provides evidence
      that vitrectomy without scleral buckling seemed to be an effective treatment for
      inferior break RD with PVR. With complete removal of vitreous and proliferative
      membranes and timing of retinectomy, the inferior breaks which complicated with
      PVR could be closed successfully without additional scleral buckling.

PMID- 23166871
TI  - Effect of low molecular weight heparin (enoxaparin) on congenital cataract
      surgery.
AB  - AIM: To assess the efficacy of intracameral enoxaparin (a low-molecular-weight
      heparin) infusion, in variable doses on postoperative inflammatory response in
      congenital cataract surgery. METHODS: It is a prospective, randomized controlled
      trial. Eighty eyes of 53 children with congenital cataract were enrolled in this
      study. Every eye had primary posterior capsulorrhexis and intraocular lens (IOL)
      implantation after lens aspiration. The eyes were divided into 4 equal groups. In
      group 1 balanced salt solution (BSS) without enoxaparin was used as an irrigation
      solution. Whereas in group 2, 3 and 4, 40mg, 20mg and 10mg enoxaparin in 500mL
      BSS was used respectively. The inflammatory response in the anterior chamber was
      compared among the groups with slit-lamp biomicroscopy. RESULTS: The mean follow
      up period was (17.75+/-3.95) months in group 1, (18.00+/-5.15) months in group 2,
      (19.20+/-5.47) months in group 3 and (18.65+/-5.16) months in group 4. Mean
      number of inflammatory cells in the anterior chamber in group 1 was significantly
      higher than that of group 2, 3, 4 (P<0.001). There was fibrin formation in the
      anterior chambers of 3 eyes in group 1 and one eye in group 4. There was
      synechiae formation in 3 eyes of group 1 and one eye of group 4. There was no
      significant difference among the groups by means of fibrin or synechiae formation
      (P>0.05). There were IOL precipitates in 4 eyes of group 1 and 2 eyes of group 4.
      IOL precipitate formation was significantly higher in group 1 than that of group
      2 and 3 in which there was no IOL precipitate (P=0.048). There was IOL
      subluxation in only one eye of group 1, 3 and 4 while no subluxation was observed
      in group 2 (P>0.05). There was no statistically significant difference detected
      about IOL subluxation occurance in all 4 groups (P>0.05). CONCLUSION:
      Complications of cataract surgery in congenital cataract patients associated with
      postoperative inflammatory response found to be decreased with the use of
      enoxaparin in intraocular infusion solutions. Furthermore according to our
      results the anti-inflammatory effect of enoxaparin was dose dependant.

PMID- 23166872
TI  - Clinical presentation of a mixed 23-gauge infusion and 20-gauge pars plana
      technique for active silicone oil removal.
AB  - AIM: To present with a clinical case series of a mixed 23-gauge infusion and 20
      gauge pars plana technique for 5,700-centipoise silicone oil removal (SOR), and
      to discuss its efficacy and safety. METHODS: This is a retrospective, non
      randomized controlled study. We performed SOR with 23-gauge infusion and 20-gauge
      active suction technique on 29 patients 29 eyes from April to October, 2011
      (mixed group). During the surgeries, a 23-gauge sclerotomy was made for infusion
      and a 20-gauge sclerotomy was used for active silicone oil suction. Anterior
      segment optical coherence tomography (OCT) was applied for 23-gauge sclerotomy
      analysis 1 day post-operation. Traditional 20-gauge SOR was performed on another
      consecutive 29 patients 29 eyes, the control group (20G group). RESULTS: There
      were 2 eyes (6.9%) in mixed group and 5 eyes (17.2%) in 20G group which had
      recurrent retinal detachment after surgery. Hopytony (IOP<=6mmHg) occurred in 8
      eyes (27.6%) of mixed group and in 10 eyes (34.5%) of 20G group post-operation,
      but all of them recovered to the normal level finally. There were no statistical
      significant differences. Final visual acuity was significantly increased after
      surgery in both groups. Anterior segment OCT images were acquired from 13 eyes of
      mixed group, and all of them had a proper wound apposition. But local ciliary
      detachment was found in 9 eyes (69%). It was hard to define the OCT image of the
      sclerotomies and ciliary body because of the serious conjunctival hemorrhages and
      chemosis in 20G group. CONCLUSION: This mixed technique is a convenient and
      effective way to remove high viscosity silicone oil. Compared with traditional 20
      gauge SOR, it does not increase the risk of post-operative complications and has
      less conjunctival reactions.. Transient postoperative hypotony is common for this
      procedure and subclinical ciliochoroidal detachment is a probable cause.

PMID- 23166873
TI  - Effects of body mass index on intraocular pressure and ocular pulse amplitude.
AB  - AIM: To investigate the effects of body mass index (BMI) on intraocular pressure
      (IOP) and ocular pulse amplitude (OPA). METHODS: Totally 140 healthy individuals
      without any systemic diseases were included in the study. BMI (kg/m(2)) was
      calculated for every individual. IOP and OPA were measured with Pascal Dynamic
      contour tonometer (DCT). Blood pressure was also measured along with the DCT. The
      patients were divided into three groups according to BMI as: Group1, BMI<25;
      Group2, 25<=BMI<30; Group3, BMI>=30. Mean values of IOP, OPA, systolic blood
      pressure (SBP) and diastolic blood pressure (DBP) were used in statistical
      analysis. RESULTS: In Group1, the means of IOP, OPA, were 16.8+/-2.3mmHg, 2.7+/
      0.7mmHg respectively; and SBP, DBP were 120.0+/-6.1mmHg, and 77.4+/-5.6mmHg
      respectively. In group2, the mean IOP, OPA, SBP, and DBP were found to be 16.6+/
      2.1mmHg, 2.4+/-0.7mmHg, 121.7+/-5.3mmHg, and 79.5+/-4.9mmHg respectively. In
      group3, the mean IOP, OPA, SBP, and DBP were found to be 17.3+/-1.7mmHg, 2.1+/
      0.7mmHg, 122.4+/-5.7mmHg, and 79.7+/-5.2mmHg respectively. There were no
      statistically significant difference between groups in terms of IOP, SBP and DBP,
      while OPA values were significantly lower in group3 (P=0.001). CONCLUSION:
      Decreased OPA values in individuals with higher BMI may indicate that subjects
      with higher BMI have lower choroidal perfusion and lower ocular blood flow.

PMID- 23166874
TI  - Tissue factor with age-related macular degeneration.
AB  - Wet age-related macular degeneration which incidence increases year by year is a
      blinding eye disease, but current clinical methods of treatment on this disease
      are limited and the outcome is not ideal. Recent studies have found abnormally
      high expression of tissue factors which are targets for the treatment of wet age
      related macular degeneration to achieve a certain effect in the choroidal
      neovascularization. Related literatures are reviewed as following.

PMID- 23166875
TI  - Research progress on the negative factors of corneal endothelial cells
      proliferation.
AB  - The human corneal endothelium forms a boundary layer between anterior chamber and
      corneal stoma. The corneal endothelial cells are responsible for maintaining
      cornea transparency, which is very vital for our visual acuity, via its pump and
      barrier functions. The adult corneal endothelial cells in vivo lack proliferation
      in response to the cell loss caused by outer damages and diseases. As a result,
      in order to compensate for cell loss, corneal endothelial cells migrate and
      enlarge while not via dividing to increase the endothelial cell density.
      Therefore, it is not capable for corneal endothelium to restore the corneal
      clarity. Some researches have proved that in vitro the corneal endothelial
      maintained proliferation ability. This review describes the current research
      progress regarding the negative factors that inhibit proliferation of the corneal
      endothelial cells. This review will mainly present several genes and proteins
      that inhibit the proliferation of the corneal endothelial cells, of course
      including some other factors like enzymes and position.

PMID- 23166876
TI  - Retinoblastoma in a young adult mimicking Coats' disease.
AB  - Retinoblastoma is the most common childhood primary intraocular malignancy, with
      the majority of cases being diagnosed before 5 years of age. Retinoblastoma in
      adults is extremely rare. Here, we report the case of a 20-year-old man who
      presented with a 3 year history of blurred vision in the right eye. Imaging did
      not reveal the typical presentation of retinoblastoma. After considering Coats'
      disease, a diagnosis of late-presenting retinoblastoma was made through
      cytological analysis. Diagnosis of retinoblastoma should be considered in the
      presence of uncertain mass lesions in the fundus of an adult.

PMID- 23166877
TI  - Superglue injuries of the eye.
AB  - AIM: To report various ocular lesions caused by accidental instillation of
      superglue. METHODS: Three cases of ocular injuries are described in children aged
      6 years, 3 years and 8 months, following accidental instillation of superglue in
      the eye. RESULTS: In the first case there was sticking of eyelashes in the medial
      1/3 of eyelids in both eyes. In the second case sticking of eye lashes was
      present in the lateral 1/3 of eyelids in the left eye. In the third case,
      superglue was present on the right cheek, above the right ear and sticking of
      eyelids in medial 1/3 in right eye. The eyelids were separated by pulling the lid
      margins with fingers in the first case and later on superglue was removed by
      trimming the eyelashes; and by direct trimming the eyelashes in second and third
      cases. There was no injury to other structures of anterior segment in the first
      two cases. However, removal of the superglue on the cornea resulted in corneal
      abrasion in the third case which healed with medical treatment and patching of
      the right eye. CONCLUSION: Accidental instillation of superglue is possible
      because of the appearance of the tube like eye ointment tube. Immediate medical
      aid will prevent ocular morbidity.

PMID- 23166878
TI  - Eye health is everyone's responsibility: China's first Western-style eye hospital
      improves in the prevention of blindness.
AB  - AIM: To investigate the relationship between China's first Western-style eye
      hospital development and the prevention of blindness in China and determine the
      main factor influencing eye health today. METHODS: Data about eye health,
      blindness and cataract surgery rate of China from public website of World Health
      Organization (WHO), ORBIS International, Ministry of Health (MOH) of China,
      Pubmed center and Historical Archives of Zhongshan Ophthalmic Center (ZOC) were
      reviewed and analyzed. RESULTS: ZOC is China's first Western-style eye hospital.
      In 2012, the ORBIS Flying Eye Hospital has chosen ZOC once again as one of its
      destinations, 30 years after ORBIS expanded internationally to train eye care
      professionals and treat underserved patients in developing countries in 1982.
      During the past 30 years, cataract surgery rate and public awareness of blindness
      prevention were improved greatly in China, in which ZOC plays a very important
      role. CONCLUSION: ZOC, as China's first Western-style eye hospital, has improved
      in the prevention of blindness. Eye health has become everyone's responsibility.

PMID- 23166879
TI  - Studies of a pedigree with limbal dermoid cyst.
AB  - AIM: To study clinical features and gene mutations within the paired-like
      homeodomain transcription factor 2 (PITX2) gene in a pedigree of bilateral limbal
      dermoids. METHODS: Complete eye examinations have been performed on each
      individual of the family. Exons of paired-like homeodomain transcription factor 2
      (PITX2) were amplified by polymerase chain reaction, sequenced, and compared with
      a reference database. RESULTS: We described the phenotype, clinic findings in a
      family with two affected members. The masses of the proband's eyes were excised
      surgically demonstrating a dermoid cyst by histopathological examination. No
      mutation was detected in the gene PITX2 in this pedigree. CONCLUSION: A family of
      limbal dermoid cyst was reported. In addition, no pathogenic sequence variations
      were found in PITX2, indicating that this phenotype in this family is a
      distinctive entity.

PMID- 23166880
TI  - Multi-modality imaging on multiple evanescent white dot syndrome-A Spectralis
      Study.
AB  - AIM: To present retinal microstructure, metabolism and function abnormalities in
      the course of multiple evanescent white dot syndrome (MEWDS) by Heidelberg
      spectralis modality imaging platform and observe its outcome by EDI-SD-OCT and
      two wavelength autofluorescence. METHODS: A case of multiple evanescent white dot
      syndrome in a 23-year-old female presented initially with a 15-day history of
      floaters and a central scotoma in the right eye. To establish the diagnosis,
      multimodality imaging was performed, namely, blue light-fundus autofluorescence
      (BL-FAF, excitation 488nm, emission >500nm), near-infrared fundus
      autofluorescence (NIR-FAF, excitation 787nm, emission >800nm) using a confocal
      scanning laser ophthalmoscope, fundus fluorescein angiography (FFA), indocyanine
      green angiography (ICGA), spectrum-domain enhance depth imaging optical coherence
      tomography (SD-EDI-OCT), multifocal electroretinography (mf-ERG) and fundus
      photogragh were performed and followed up at the eighth month after initially
      visiting. RESULTS: Optical coherence tomography (OCT) showed a transient
      disruption of the foveal photoreceptor outer segments in correspondence to foveal
      granularity. NIR-FAF showed hypoautofluorescent areas, <=40um in size, mostly
      concentrated around the posterior pole and its temporal side less than that in BL
      FAF. Mf-ERG show pinnacle disappeared in fovea and macula and responses decreased
      markedly compared with the follow eye. At the eighth month follow up,
      hyperfluorescence in BL-FAF were disappear, while, NIR-FAF Hypofluorescent spots
      in early stage of such lesion were reduced. But OCT demonstrated the structure
      was recovered in residual Hypofluorescent area in NIR-FAF. The subfoveal
      choroidal thickness was decreased from 372um to 307um slightly and cost line was
      recovered. CONCLUSION: MEWDS is a benign self-healing disease and there is no
      pathological evidence to investigate the natural course of such disease. SD-OCT
      allows highly detailed images approaching histopathology to certify the
      microstructural changes. Two-wave length FAF and mf-ERG provide more information
      about metabolism in outer retina especial RPE and photoreceptor. Spectralis OCT
      combined with two-wavelength FAF and mf-ERG provide a new way to analyze this
      disease and offer more details for therapy and follow-up.

PMID- 23166881
TI  - Cataract surgery and intraocular lens implantation in anterior megalophthalmos.

PMID- 23166882
TI  - Abruptly developed large esotropia after full time occlusion therapy in
      anisometropic amblyopia.

PMID- 23166883
TI  - Jerky see-saw nystagmus in internuclear ophthalmoplegia from a lower pontine
      lesion.

PMID- 23166885
TI  - Surgical completeness of total thyroidectomy using harmonic scalpel: comparison
      with conventional total thyroidectomy in papillary thyroid carcinoma patients.
AB  - PURPOSE: THE AIM OF THIS STUDY WAS TO COMPARE THE SURGICAL COMPLETENESS AND
      OUTCOME OF TOTAL THYROIDECTOMY IN TWO PATIENT GROUPS: One treated by harmonic
      scalpel (HS) and one by conventional total thyroidectomy (CT). METHODS: Between
      March 2006 and December 2007, 104 patients had total thyroidectomy by HS and 108
      patients underwent CT. We analyzed clinicopathological characteristics and
      stimulated serum thyroid-stimulating hormone (TSH), thyroglobulin (Tg), and anti
      Tg antibodies at the time of ablation for both groups. RESULTS: Compared with the
      CT group, the HS group had shorter operating time and hospital stays and reduced
      postoperative drainage. At postsurgical ablation, mean serum TSH was 80.47 +/-
      21.77 mU/L in the HS group and 69.74 +/- 21.17 mU/L in the CT group, with
      significant between-group differences (P < 0.001). Mean serum Tg levels after TSH
      stimulation were 1.57 +/- 3.17 and 3.95 +/- 10.14 ng/mL in the HS and CT groups,
      respectively, with significant between-group differences (P = 0.028). CONCLUSION:
      Total thyroidectomy with an HS is a relatively safe and effective technique for
      use in patients with PTC. The HS provides surgical completeness and has a
      beneficial effect on successful ablation.

PMID- 23166886
TI  - Risk factors associated with delayed gastric emptying after subtotal gastrectomy
      with Billroth-I anastomosis using circular stapler for early gastric cancer
      patients.
AB  - PURPOSE: Gastric surgery may potentiate delayed gastric emptying. Billroth I
      gastroduodenostomy using a circular stapler is the most preferable reconstruction
      method. The purpose of this study is to analyze the risk factors associated with
      delayed gastric emptying after radical subtotal gastrectomy with Billroth I
      anastomosis using a stapler for early gastric cancer. METHODS: Three hundred and
      seventy-eight patients who underwent circular stapled Billroth I
      gastroduodenostomy after subtotal gastrectomy due to early gastric cancer were
      analyzed retrospectively. One hundred and eighty-two patients had Billroth I
      anastomosis using a 25 mm diameter circular stapler, and 196 patients had
      anastomosis with a 28 or 29 mm diameter circular stapler. Clinicopathological
      features and postoperative outcomes were evaluated and compared between the two
      groups. Delayed gastric emptying was diagnosed by symptoms and simple abdomen X
      ray with or without upper gastrointestinal series or endoscopy. RESULTS:
      Postoperative delayed gastric emptying was found in 12 (3.2%) of the 378
      patients. Among all the variables, distal margin and circular stapler diameter
      were significantly different between the cases with delayed gastric emptying and
      no delayed gastric emptying. There were statistically significant differences in
      sex, body mass index, comorbidity, complication, and operation type according to
      circular stapler diameter. In both univariate and multivariate logistic
      regression analyses, only the stapler diameter was found to be a significant
      factor affecting delayed gastric emptying (P = 0.040). CONCLUSION: In this study,
      the circular stapler diameter was one of the most significant predictable factors
      of delayed gastric emptying for Billroth I gastroduodenostomy. The use of a 28 or
      29 mm diameter circular stapler rather than a 25 mm diameter stapler in stapled
      gastroduodenostomy for early gastric cancer can reduce postoperative delayed
      gastric emptying associated with anastomosic stenosis or edema with relative
      safety.

PMID- 23166884
TI  - Age and prognosis of papillary thyroid carcinoma: retrospective stratification
      into three groups.
AB  - PURPOSE: We investigated the prognosis according to age in papillary thyroid
      carcinoma (PTC) patients. METHODS: We retrospectively evaluated 2,890 patients
      who underwent thyroidectomy due to PTC between May 2004 and Aug 2008. We divided
      patients into 3 groups: young (<=35 years old), middle (between 35 and 54 years
      old), and old (>=55 years old). RESULTS: Median age was 47.0 years old (range, 15
      to 82 years). Within a follow-up period median of 50 months, there were 148
      (5.1%) locoregional recurrences, 6 (0.2%) PTC-related deaths, and 18 (0.6%) PTC
      unrelated deaths. Outcomes were more favorable in the young group, with no PTC
      related death despite the frequent locoregional recurrence. In the old group
      compared to the middle, there was a higher proportion of male, and more
      aggressive types as T3 or N1b, higher mean tumor number, more multiplicity, and
      bilaterality. The old group of >=55 years did not show a significant difference
      in PTC-related deaths than other age groups in Cox analysis (OR, 0.9; P = 0.677),
      but a significant cutoff age in PTC-related deaths at 62.5 years was determined
      in ROC analysis (area under curve = 0.912). CONCLUSION: We showed that the <=35
      years group shows favorable prognosis despite the frequent locoregional
      recurrence and >=62.5 years group shows a poor prognosis regardless of other
      factors such as male sex or tumor aggressiveness. Further multiinstitutional
      studies are needed to elucidate the prognosis according to patient's age.

PMID- 23166887
TI  - Short-term outcomes after laparoscopic surgery following preoperative
      chemoradiotherapy for rectal cancer.
AB  - PURPOSE: The safety and the feasibility of performing laparoscopic surgery for
      rectal cancer after preoperative chemoradiotherapy (CRT) have not yet been
      established. Thus, the aim of this study was to evaluate the efficacy and the
      safety of laparoscopic rectal cancer surgery performed after preoperative CRT.
      METHODS: We enrolled 124 consecutive patients who underwent laparoscopic surgery
      for rectal cancer. Of these patients, 56 received preoperative CRT (CRT group),
      whereas 68 did not (non-CRT group). The patients who were found to have distant
      metastasis and open conversion during surgery were excluded. The
      clinicopathologic parameters were evaluated and the short-term outcomes were
      compared between the CRT and non-CRT groups. RESULTS: The mean operation time was
      longer in the CRT group (294 minutes; range, 140 to 485 minutes; P = 0.004). In
      the non-CRT group, the tumor sizes were larger (mean, 4.0 cm; range, 1.2 to 8.0
      cm; P < 0.001) and more lymph nodes were harvested (mean, 12.9; range, 0 to 35; P
      < 0.001). However, there was no significant difference between the two groups in
      time to first bowel movement, tolerance of a soft diet, length of hospital stay,
      and postoperative complication rate. CONCLUSION: Performing laparoscopic surgery
      for rectal cancer after preoperative CRT may be safe and feasible if performed by
      a highly skilled laparoscopic surgeon. Randomized controlled trials and long-term
      follow-up studies are necessary to support our results.

PMID- 23166888
TI  - Early postoperative and long-term oncological outcomes of laparoscopic treatment
      for patients with familial adenomatous polyposis.
AB  - PURPOSE: We evaluated the short- and long-term outcomes of laparoscopic total
      proctocolectomy with ileal pouch-anal anastomosis (TPC/IPAA) for treatment of
      familial adenomatous polyposis (FAP). Also, we assessed the oncologic outcomes in
      FAP patients with coexisting malignancy. METHODS: From August 1999 to September
      2010, 43 FAP patients with or without coexisting malignancy underwent TPC/IPAA by
      a laparoscopic-assisted or hand-assisted laparoscopic surgery. RESULTS: The
      median age was 33 years (range, 18 to 58 years) at the time of operation. IPAA
      was performed by a hand-sewn method in 21 patients (48.8%). The median operative
      time was 300 minutes (range, 135 to 610 minutes), which reached a plateau after
      22 operations. Early postoperative complications within 30 days occurred in 7
      patients (16.3%) and long-term morbidity occurred in 15 patients (34.9%)
      including 6 (14.0%) with desmoid tumors and 3 (7.0%) who required operative
      treatment. Twenty-two patients (51.2%) were diagnosed with coexisting colorectal
      malignancy. The median follow-up was 58.5 months (range, 7.9 to 97.8 months).
      There was only 1 case of local recurrence in the pelvic cavity. No cases of
      adenocarcinoma at the residual rectal mucosa developed. 5-year disease-free
      survival rate for 22 patients who had coexisting malignancy was 86.5% and 5-year
      overall survival rate was 92.6%. Three patients died from pulmonary or hepatic
      metastasis. CONCLUSION: Laparoscopic TPC/IPAA in patients with FAP is feasible
      and offers favorable postoperative outcomes. It also delivered acceptable
      oncological outcomes in patients with coexisting malignancy. Therefore,
      laparoscopic TPC/IPAA may be a favorable treatment option for FAP.

PMID- 23166889
TI  - Immediately transcripted genes in various hepatic ischemia models.
AB  - PURPOSE: To elucidate the characteristic gene transcription profiles among
      various hepatic ischemia conditions, immediately transcribed genes and the degree
      of ischemic injury were compared among total ischemia (TI), intermittent clamping
      (IC), and ischemic preconditioning (IPC). METHODS: Sprague-Dawley rats were
      equally divided into control (C, sham-operated), TI (ischemia for 90 minutes), IC
      (ischemia for 15 minutes and reperfusion for 5 minutes, repeated six times), and
      IPC (ischemia for 15 minutes, reperfusion for 5 minutes, and ischemia again for
      90 minutes) groups. A cDNA microarray analysis was performed using hepatic
      tissues obtained by partial hepatectomy after occluding hepatic inflow. RESULTS:
      THE CDNA MICROARRAY REVEALED THE FOLLOWING: interleukin (IL)-1beta expression was
      2-fold greater in the TI group than in the C group. In the IC group, IL
      1alpha/beta expression increased by 2.5-fold, and Na+/K+ ATPase beta1 expression
      decreased by 2.4-fold. In the IPC group, interferon regulatory factor-1,
      osteoprotegerin, and retinoblastoma-1 expression increased by approximately 2
      fold compared to that in the C group, but the expression of Na+/K+ ATPase beta1
      decreased 3-fold. CONCLUSION: The current findings revealed characteristic gene
      expression profiles under various ischemic conditions. However, additional
      studies are needed to clarify the mechanism of protection against IPC.

PMID- 23166890
TI  - Treatment of failing vein grafts in patients who underwent lower extremity
      arterial bypass.
AB  - PURPOSE: We attempted to determine risk factors for the development of failing
      vein graft and optimal treatment in patients with infrainguinal vein grafts.
      METHODS: We retrospectively reviewed a database of patients who underwent
      infrainguinal bypass using autogenous vein grafts due to chronic atherosclerotic
      arterial occlusive disease of lower extremity (LE) at a single institute between
      September 2003 and December 2011. After reviewing demographic, clinical, and
      angiographic features of the patients with failing grafts, we analyzed those
      variables to determine risk factors for the development of failing grafts. To
      determine an optimal treatment for the failing vein grafts, we compared results
      of open surgical repair (OSR), endovascular treatment (EVT) and conservative
      treatment. RESULTS: Two hundred and fifty-eight LE arterial bypasses using
      autogenous vein grafts in 242 patients were included in this study. During the
      follow-up period of 39 +/- 25 months (range, 1 to 89 months), we found 166 (64%)
      patent grafts with no restenosis, 41 (15.9%) failing grafts, 39 (15.1%) graft
      occlusions, and 12 (4.7%) grafts lost in follow-up. In risk factor analysis for
      the development of a failing graft, no independent risk factors were identified.
      After 50 treatments of the 41 failing grafts (24 OSR, 18 EVT, 8 conservative
      management), graft occlusion was significantly more common in conservative
      treatment group and severe (>75%) restenosis was significantly more common
      following EVT than OSR (P = 0.001). Reintervention-free graft patency was also
      superior in the OSR group to that of the EVT group (87% vs. 42%, P = 0.015).
      CONCLUSION: OSR of failing grafts has better outcomes than EVT or conservative
      management in treating failing grafts.

PMID- 23166891
TI  - Radical resection of intestinal blue rubber bleb nevus syndrome.
AB  - Blue rubber bleb nevus syndrome (BRBNS) is a rare systemic vascular disorder
      characterized by multiple venous malformations involving many organs. BRBNS can
      occur in various organs, but the most frequently involved organs are the skin and
      gastrointestinal (GI) tract. GI lesions of BRBNS can cause acute or chronic
      bleeding, and treatment is challenging. Herein, we report a case of GI BRBNS that
      was successfully treated with a combination of intraoperative endoscopy and
      radical resection.

PMID- 23166892
TI  - Sarcomatoid carcinoma of the small intestine: a rare and highly aggressive tumor.
AB  - Sarcomatoid carcinoma of the small intestine is an extremely rare malignant
      neoplasm that usually has a poor prognosis. We report a case of sarcomatoid
      carcinoma arising in the small intestine in a 62-year-old man who was
      hospitalized for abdominal pain. Computed tomography revealed wall thickening of
      the small intestine. The resected specimen showed a gray-whitish solid mass with
      hemorrhage and necrosis. Microscopically, the tumor was composed of pleomorphic
      spindle and discohesive polygonal cells with frequent mitosis. No carcinomatous
      component was recognized. Immunohistochemistry revealed coexpression of
      cytokeratin and vimentin by the tumor cells, whereas expressions of C-kit, CD34,
      HMB-45, smooth muscle actin, and desmin were negative. The diagnosis was
      sarcomatoid carcinoma of the small intestine.

PMID- 23166893
TI  - Bowel infarction due to intestinal mucormycosis in an immunocompetent patient.
AB  - Mucormycosis is a fatal opportunistic fungal infection that typically occurs in
      immunocompromised patients. The classical manifestation of mucormycosis is a
      rhinocerebral infection, and although primary gastrointestinal infection is
      uncommon, it has an extremely high mortality rate in immunocompromised patients.
      Furthermore, cases of gastrointestinal mucormycosis in an immunocompetent host
      are rarely reported. Here, we describe our experience of a male patient, with no
      underlying disease, who succumbed to a bowel infarction caused by intestinal
      mucormycosis during mechanical ventilatory care for severe pneumonia and septic
      shock.

PMID- 23166894
TI  - Pancreatic hamartoma diagnosed after surgical resection.
AB  - A pancreatic hamartoma is a rare benign lesion that may be mistaken for
      malignancy. A pancreatic hamartoma can present with vague, non-specific symptoms,
      which can be difficult to diagnose despite modern diagnostic tools. We report
      here a pancreatic hamartoma diagnosed after surgical resection. A 52-year-old
      female presented with postprandial abdominal discomfort. Abdominal computed
      tomography and pancreatic magnetic resonance imaging revealed a 2.2 * 2.5-cm
      cystic mass in the pancreatic head. The patient underwent a pylorus-preserving
      pancreaticoduodenectomy. The histopathological and immunohistochemical studies
      helped make the diagnosis of pancreatic hamartoma. Here, we report a case of
      pancreatic hamartoma and review the relevant medical literature.

PMID- 23166896
TI  - Canadian Association of Gastroenterology Research Committee Report 2012.

PMID- 23166895
TI  - Design and methods of the Adult Inuit Health Survey 2007-2008.
AB  - BACKGROUND: The Canadian International Polar Year (IPY) program made it possible
      to undertake much needed health research in 3 jurisdictions within the Canadian
      Inuit Nunangat (homeland) over a 2-year period: Inuvialuit Settlement Region
      (ISR), Nunavut Territory, and Nunatsiavut. DESIGN: The Adult Inuit Health Survey
      (IHS) was a cross-sectional survey and provides baseline data upon which future
      comparisons can be made for prospectively assessing factors leading to the
      progression of chronic diseases among Canadian Inuit. With the help of the
      Canadian Coast Guard Ship Amundsen, which was equipped with research and
      laboratory facilities, 33 coastal communities were visited; land survey teams
      visited 3 inland communities. RESULTS: The Adult IHS succeeded in obtaining
      important baseline information concerning the health status and living conditions
      of 2,595 adults living in ISR, Nunavut and Nunatsiavut. CONCLUSION: Information
      from this survey will be useful for future comparisons and the opportunity to
      link with the International Inuit Cohort, a follow-up evaluation, and for the
      development of future health policies and public health interventions.

PMID- 23166897
TI  - Gangliocytic paraganglioma of the duodenum.

PMID- 23166898
TI  - Endoscopic mucosal resection of esophageal squamous papillomatosis.

PMID- 23166899
TI  - Waiting for a consultation: Sorry, but the doctor cannot see you.

PMID- 23166900
TI  - The 'natural history' of declined outpatient gastroenterology referrals.
AB  - OBJECTIVE: To evaluate the 'natural history' of outpatients who were referred to
      the Division of Gastroenterology at the University of Alberta Hospital (Edmonton,
      Alberta) for gastrointestinal problems and were subsequently declined. METHODS:
      Patients were tracked for 12 months after they were referred and declined for the
      following indications: abdominal pain, rectal bleeding, fecal occult blood test
      positive stools and iron deficiency. For each patient, data regarding
      consultations by other gastroenterologists or surgeons working in the region,
      clinically relevant diagnoses and the number of gastrointestinal-related x-rays
      performed were obtained. RESULTS: Of a total sample size of 230 patients, 110
      (47.8%) were seen by another gastroenterologist or surgeon after decline. A
      significant diagnosis was made in 21 patients (9.1%), which had immediate
      clinical consequences in 29%. Forty per cent of patients underwent one or more
      gastointestinal-related x-rays before being declined, which increased to 55%
      after decline. CONCLUSION: Approximately 50% of declined patients were seen by
      other gastroenterologists or surgeons in the region. In 9.1% of these patients, a
      clinically important diagnosis was made, of which one-quarter had immediate
      medical consequences.

PMID- 23166901
TI  - Different screening definitions have little impact on polypectomy rate estimates.
AB  - BACKGROUND: Polypectomy rate is a surrogate quality indicator for screening
      colonoscopy. Various methods for identifying screening colonoscopies have been
      used and it is unclear how different definitions affect the estimated polypectomy
      rate. OBJECTIVE: To estimate polypectomy rates and how they vary according to the
      definition of a screening colonoscopy, using patient- and endoscopist-reported
      indications. METHODS: A cross-sectional analysis of endoscopists and their
      patients 50 to 75 years of age who underwent colonoscopy was conducted. Based on
      questionnaire responses, four patient indications were derived: perceived
      screening; perceived nonscreening; medical history indicating nonscreening; and
      combination of the three indications. Endoscopist indication was derived from a
      questionnaire completed immediately after colonoscopy. Polypectomy status was
      obtained from provincial physician billing records. Polypectomy rates were
      computed, while accounting for physician and hospital level clustering, using all
      four patient indications, endoscopist indication, and the agreement between
      patient and endoscopist indications. The effect of indications on polypectomy
      rate was estimated adjusting for age, sex and family history of colorectal
      cancer. RESULTS: A total of 2134 patients and 45 endoscopists were included. The
      proportion of colonoscopies classified as screening according to the nine
      indications ranged from 32.2% to 70.9%. Polypectomy rates ranged between 22.6%
      and 26.2% for screening colonoscopy, and between 27.1% and 30.8% for nonscreening
      colonoscopy. Adjusted ORs for indication ranged between 0.74 and 0.94.
      DISCUSSION: Although the proportion of colonoscopies identified as screening
      varied considerably among the indications, the estimated polypectomy rates were
      similar. CONCLUSION: The findings suggest that the way screening is defined does
      not greatly affect the estimates of polypectomy rate.

PMID- 23166902
TI  - Survey of perceptions and practices among Canadian gastroenterologists regarding
      the prevention of venous thromboembolism for hospitalized inflammatory bowel
      disease patients.
AB  - BACKGROUND: Patients with inflammatory bowel disease (IBD) who are hospitalized
      with disease flares are known to be at an increased risk of venous
      thromboembolism (VTE). This is a preventable complication; however, there is
      currently no standardized approach to the prevention and management of VTE.
      OBJECTIVES: To characterize the opinions and general prophylaxis patterns of
      Canadian gastroenterologists and IBD experts. METHODS: A survey questionnaire was
      sent to Canadian gastroenterologists affiliated with a medical school or IBD
      referral centre. Participants were required to be practicing physicians who had
      completed all of their training and had been involved in the care of IBD patients
      within the previous 12 months. Various clinical scenarios were presented and
      demographic data were solicited. RESULTS: The majority of respondents were
      practicing in an academic setting (95%) and considered themselves to be IBD
      experts or subspecialists (71%). Eighty-three per cent reported providing VTE
      prophylaxis most, if not all of the time, and most (96%) used pharmacological
      prophylaxis alone, usually heparin or one of its analogues. There was less
      consistency among respondents with respect to whether IBD patients in remission,
      but admitted for another condition, should be given prophylaxis. There was also
      less agreement regarding the duration of anticoagulation in patients with
      confirmed VTE. CONCLUSION: There was a general consensus among academic
      gastroenterologists that IBD inpatients are at an increased risk for VTE and
      would benefit from VTE prophylaxis. However, areas of uncertainty still exist and
      the IBD community would benefit from evidence-based clinical practice guidelines
      to standardize the management of this important problem.

PMID- 23166904
TI  - Cardiac work-up protocol for liver transplant candidates: experience from a
      single liver transplant centre.
AB  - BACKGROUND: Ischemic cardiac events can cause significant morbidity and mortality
      postliver transplantation; however, no validated protocols to screen patients
      before transplantation exist. OBJECTIVES: To report the introduction of a
      noninvasive cardiac screening protocol used at the Liver Unit, University of
      Calgary (Calgary, Alberta); to determine whether the protocol decreases use of
      coronary angiograms; and to compare cardiac outcomes using the new protocol with
      an appropriately matched historical control group. METHODS: A new cardiac
      screening protocol was introduced into the program in 2005, which uses perfusion
      scintigraphy to screen high-risk cardiac patients, reserving coronary angiograms
      for abnormal results. Transplanted patients screened using this protocol were
      compared with matched historical controls. Electronic charts were reviewed for
      cardiac outcomes intra- and postliver transplantation. RESULTS: A total of 396
      patients were screened between April 2005 and February 2009. Eighty-two were
      transplanted by February 2009 and included in the study. Eighty-one patients were
      successfully matched according to age, sex, cardiac history and presence of
      diabetes. Twelve of 82 (14.6%) and 11 of 81 (13.6%) in the study and control
      groups, respectively, underwent coronary angiograms (P=0.85). Coronary artery
      disease was found in six of 12 (50.0%) study patients and three of 11 (27.3%)
      control patients who underwent coronary angiography (P=0.27). The mean (+/- SD)
      length of the follow-up period was 1.87+/-0.91 years and 4.45+/-1.89 years in the
      study and control groups, respectively. One of 81 in the control group and zero
      of 82 in the study group experienced an acute coronary syndrome event
      postoperatively. CONCLUSIONS: Coronary events are infrequent in liver transplant
      recipients. The described protocol is an effective method of coronary artery
      disease screening before liver transplant but does not reduce the number of
      cardiac investigations performed.

PMID- 23166903
TI  - Blood cytokine, chemokine and gene expression in cholestasis patients with
      intractable pruritis treated with a molecular adsorbent recirculating system: a
      case series.
AB  - BACKGROUND: The molecular adsorbent recirculating system (MARS) is an albumin
      dialysis modality that has been investigated predominantly in patients with acute
      and acute-on-chronic liver failure. OBJECTIVES: To report the clinical efficacy
      and safety of MARS therapy for intractable pruritus in cholestasis patients with
      stable chronic liver disease, characterizing the impact of MARS on cytokine
      levels and on the transcriptome in the blood compartment. METHODS: MARS therapy
      was performed on three patients with cholestatic liver disease using 8 h runs for
      two consecutive days. The expression levels of 65 cytokines/chemokines and 24,000
      genes were profiled by Luminex (Luminex Corporation, USA) and microarray,
      respectively. RESULTS: A quality-of-life assessment demonstrated a marked
      improvement during therapy, which was sustained in two of three patients. No
      bleeding or infectious complications were observed. Bile acid levels were
      markedly reduced following MARS (mean [+/- SD] pretreatment 478.9+/-112.2 umol/L
      versus post-treatment 89.7+/-68.8 umol/L). Concordant decreases in
      cytokine/chemokine levels were noted for interleukin (IL)-1beta, IL-2, IL-6, IL
      8, IL-12 (p40), RANTES, tranforming growth factor-alpha, tumour necrosis factor
      alpha and thrombopoietin following MARS. On microarray profiling, biologically
      relevant concordant changes among all patients were evident for 20 different
      genes (10 upregulated and 10 downregulated). The upregulation of several
      potentially immune suppressive/regulatory genes (eg, early growth response 3 [EGR
      3], ephrin-A2 [EFNA2] and serum amyloid A1 [SAA1]), concurrent with
      downregulation of genes involved in innate immunity (eg, toll-like receptor 4
      interactor with leucine-rich repeats [TRIL]) and inflammation (eg, ephrin
      receptor B1 [EPHB1]), was observed. CONCLUSIONS: This investigative approach
      offers new insights into intractable pruritus and suggests future therapeutic
      targets. The clinical benefit of MARS in cholestasis patients with intractable
      pruritus may not exclusively result from filtration of pruritogens, but also from
      systemic changes in cytokine/chemokine levels and changes in gene expression of
      blood cells.

PMID- 23166905
TI  - Inflammatory bowel disease: a Canadian burden of illness review.
AB  - BACKGROUND: Inflammatory bowel diseases (IBD) - Crohn's disease (CD) and
      ulcerative colitis (UC) - significantly impact quality of life and account for
      substantial costs to the health care system and society. OBJECTIVE: To conduct a
      comprehensive review and summary of the burden of IBD that encompasses the
      epidemiology, direct medical costs, indirect costs and humanistic impact of these
      diseases in Canada. METHODS: A literature search focused on Canadian data
      sources. Analyses were applied to the current 2012 Canadian population. RESULTS:
      There are approximately 233,000 Canadians living with IBD in 2012 (129,000
      individuals with CD and 104,000 with UC), corresponding to a prevalence of 0.67%.
      Approximately 10,200 incident cases occur annually. IBD can be diagnosed at any
      age, with typical onset occurring in the second or third decade of life. There
      are approximately 5900 Canadian children <18 years of age with IBD. The economic
      costs of IBD are estimated to be $2.8 billion in 2012 (almost $12,000 per IBD
      patient). Direct medical costs exceed $1.2 billion per annum and are driven by
      cost of medications ($521 million), hospitalizations ($395 million) and physician
      visits ($132 million). Indirect costs (society and patient costs) total $1.6
      billion and are dominated by long-term work losses of $979 million. Compared with
      the general population, the quality of life patients experience is low across all
      dimensions of health. CONCLUSIONS: The present review documents a high burden of
      illness from IBD due to its high prevalence in Canada combined with high per
      patient costs. Canada has among the highest prevalence and incidence rates of IBD
      in the world. Individuals with IBD face challenges in the current environment
      including lack of awareness of IBD as a chronic disease, late or inappropriate
      diagnosis, inequitable access to health care services and expensive medications,
      diminished employment prospects and limited community-based support.

PMID- 23166907
TI  - A compact analytical formalism for current transients in electrochemical systems.
AB  - Micro- and nanostructured electrodes form an integral part of a wide variety of
      electrochemical systems for biomolecular detection, batteries, solar cells,
      scanning electrochemical microscopy, etc. Given the complexity of the electrode
      structures, the Butler-Volmer formalism of redox reactions, and the diffusion
      transport of redox species, it is hardly surprising that only a few problems are
      amenable to closed-form, compact analytical solutions. While numerical solutions
      are widely used, it is often difficult to integrate the insights gained into the
      design and optimization of electrochemical systems. In this article, we develop a
      comprehensive analytical formalism for current transients that not only
      anticipate the responses of complex electrode structures to complicated
      voltammetry measurements, but also intuitively interpret diverse experiments such
      as redox detection of molecules at nanogap electrodes, scanning electrochemical
      microscopy, etc. The results from the analytical model, well supported through
      detailed numerical simulations and experimental data from the literature, have
      broad implications in the design and optimization of nanostructured electrodes
      for healthcare and energy storage applications.

PMID- 23166908
TI  - Spot morphology of non-contact printed protein molecules on non-porous substrates
      with a range of hydrophobicities.
AB  - Non-contact inkjet printing technology is one of the most promising tools for
      producing microarrays. The quality of the microarray depends on the type of the
      substrate used for printing biomolecules. Various porous and non-porous
      substrates have been used in the past, but due to low production cost and easy
      availability, non-porous substrates like glass and plastic are preferred over
      porous substrates. On these non-porous substrates, obtaining spot uniformity and
      a high signal to noise ratio is a big challenge. In our research work, we have
      modified pristine glass slides using various silanes to produce a range of
      hydrophobic glass substrates. The hydrophobicities of the slides expressed in the
      contact angle (theta) of a sessile drop of water were 49 degrees , 61 degrees ,
      75 degrees , 88 degrees  and 103 degrees . Using a non-contact inkjet printer,
      microarrays of biotinylated biomolecules (BSA and IgG) were produced on these
      modified glass substrates, pristine (untreated) glass and also on HTA polystyrene
      slides. The uniformity of the spots, reflecting the distribution of the
      biomolecules in the spots, was analyzed and compared using confocal laser
      scanning microscopy (CLSM). The quality of the spots was superior on the glass
      slide with a contact angle of ~75 degrees . We also investigated the influence of
      the hydrophobicity of the substrate on a two-step, real diagnostic antibody
      assay. This nucleic acid microarray immunoassay (NAMIA) for the detection of
      Staphylococcus aureus showed that on highly hydrophilic (theta < 10 degrees ) and
      hydrophobic substrates (theta > 100 degrees ) the assay signal was low, whereas
      an excellent signal was obtained on the substrates with intermediate contact
      angles, theta    ~ 61 degrees  and theta    ~ 75 degrees , respectively.

PMID- 23166906
TI  - Evaluation and management of skeletal health in celiac disease: position
      statement.
AB  - OBJECTIVE: To review the evaluation and management of skeletal health in patients
      with celiac disease (CD), and to make recommendations on screening, diagnosis,
      treatment and follow-up of low bone mineral density (BMD) in CD patients.
      METHODS: A multidisciplinary team developed clinically relevant questions for
      review. An electronic search of the literature was conducted using the MEDLINE
      and EMBASE databases from 1996 to 2010. All original studies, reviews and
      guidelines, both pediatric and adult, were included. A document summarizing the
      results of the review and proposed recommendations was prepared and underwent
      multiple revisions until consensus was reached. RESULTS: At diagnosis,
      approximately one-third of adult CD patients have osteoporosis, one-third have
      osteopenia and one-third have normal BMD. Children with CD have low bone mass at
      diagnosis. Adult and pediatric CD patients are at increased risk of fractures.
      DISCUSSION: For adults, serum calcium, albumin, 25(OH) vitamin D3, parathyroid
      hormone and 24 h urine calcium testing should be performed at diagnosis; patients
      with 'classic' CD and those at risk for osteoporosis should undergo a dual x-ray
      absorptiometry scan. An abnormal baseline dual x-ray absorptiometry scan should
      be repeated one to two years after initiation of a gluten-free diet (GFD). For
      children, BMD should be assessed one year after diagnosis if GFD adherence is not
      strict. A GFD is the most important treatment for bone loss. Supplemental
      antiresorptives may be justified in those who remain at high fracture risk (eg,
      postmenopausal women, older men) after implementation of a GFD. CONCLUSION:
      Current evidence does not support the screening of all CD patients for low BMD at
      diagnosis. Follow-up BMD assessment should be performed one to two years after
      initiation of a GFD.

PMID- 23166909
TI  - A selective amperometric sensing platform for lead based on target-induced strand
      release.
AB  - A novel strategy for selective and sensitive amperometric detection of lead ion
      (Pb(2+)) was proposed based on target-induced strand release. The underlying gold
      electrode was pre-modified with dendritic gold nanoparticles by direct
      electrodeposition to afford increased electrode surface area for immobilization
      of thiol group-containing capture DNA molecules. The hybridization of the capture
      DNA molecules with Pb(2+)-specific aptamer molecules to form a DNA duplex, into
      which methylene blue was intercalated, induced measurable electrochemical signal.
      Upon addition of Pb(2+), it could specifically bind to its aptamer to form Pb(2+)
      stablized G-quadruplex and induce the aptamer strand to release from the
      electrode surface into solution, accompanied by the release of intercalated MB
      responsible for significant signal reduction. The fabricated biosensor showed a
      linear response to the logarithm of Pb(2+) concentration over the range of 1.0 *
      10(-10) M to 1.0 * 10(-7) M with a detection limit of 7.5 * 10(-11) M. In
      addition, this strategy afforded an exquisite selectivity for Pb(2+) against
      other metal ions. The excellent sensitivity and selectivity show good potential
      for Pb(2+) detection in real environmental samples.

PMID- 23166911
TI  - Shape-selective growth of silver nanoparticles under continuous flow
      photochemical conditions.
AB  - A microfluidic setup for the photochemical nucleation and growth of silver
      nanoparticles with controlled morphologies is described. The combination of
      microstructured reactors and efficient LED illumination speeds the growth process
      up and enhances the shape-wise homogeneity of the produced nanostructures.

PMID- 23166910
TI  - A bio-inspired sensor based on surfactant film and Pd nanoparticles.
AB  - A bio-inspired complex, [(bpbpmp)Fe(III)(m-OAc)(2)Cu(II)](ClO(4)), was combined
      with a zwitterionic surfactant (ImS3-14) stabilizing pre-formed palladium
      nanoparticles and coated on a glassy carbon electrode (GCE). This bio-inspired
      surfactant film was capable of catalyzing redox reactions of dihydroxybenzenes,
      thus allowing the simultaneous electrochemical quantification of CC and HQ in
      cigarette residue samples by square-wave voltammetry (SWV). The best experimental
      conditions were obtained using phosphate buffer solution (0.1 mol L(-1), pH 7.0),
      with 1.3 nmol of the bio-inspired complex, 0.15 MUmol of the surfactant and 1.08
      nmol of Pd. The best voltammetric parameters were: frequency 100 Hz, pulse
      amplitude 40 mV and step potential 8 mV. The limits of detection calculated from
      simultaneous curves were found to be 2.2 * 10(-7) and 2.1 * 10(-7) mol L(-1) for
      HQ and CC respectively.

PMID- 23166912
TI  - Blastic transformation of mantle cell lymphoma.

PMID- 23166914
TI  - IPARZINE-SKR study: randomized, double-blind clinical trial of a new topical
      product versus placebo to prevent pressure ulcers.
AB  - This study compared the efficacy of a new topical agent (IPARZINE-4A-SKR) on
      preventing category I pressure ulcers (PUs) over a 2-week period, compared with a
      placebo. A double-blind, randomised, multi-centre, placebo-controlled clinical
      trial in two parallel groups was conducted. The primary objective was to compare
      PU incidence between groups. Hospital and socio-sanitary centre patients (n =
      194) at risk of developing a PU (Braden scale) were randomised into two groups.
      The intervention group included 99 patients, and the placebo group comprised 95
      patients. Patients were comparable in terms of age, sex and PU risk. In both
      groups, patients had a high risk of developing PUs. The product was applied on
      the sacrum, trochanters and heels. Six PUs (incidence = 6.1%) were detected in
      the intervention group versus seven (incidence = 7.4%) in the placebo group.
      Differences were not statistically significant (z = 0.08; P = 0.94), relative
      risk = 0.82 (95% confidence interval = 0.29-2.36). The main limitation of the
      study was the sample size and, therefore, the main difficulty encountered was in
      determining whether the product is ineffective or simply has not been used with
      sufficient patients. In conclusion, it is not possible to confirm that there are
      any differences between the studied and the placebo treatments in the prevention
      of PUs. The results obtained were similar to those obtained in studies of PU
      prevention using products based on topical fatty acids.

PMID- 23166915
TI  - [Gambling addiction: always on the hunt for the next kicks].

PMID- 23166916
TI  - Retracted: The pre-synaptic metabotropic glutamate receptor 7 "mGluR7" is a
      critical modulator of ethanol sensitivity in mice [Neuroscience 199 (2011) 13
      23].

PMID- 23166918
TI  - Psychiatrist and journalist win prize for defending science.

PMID- 23166917
TI  - Diagnosis of rejection after liver transplantation: use of phosphorus-31 magnetic
      resonance spectroscopy ((31)P-MRS).
AB  - BACKGROUND: In vivo hepatic phosphorus-31 magnetic resonance spectroscopy (31)P
      MRS) provides non-invasive information about phospholipid metabolism. AIMS: To
      delineate (31)P-MRS abnormalities in patients with chronic rejection and to
      characterize spectral changes by pathology. PATIENTS AND METHODS: Sixty-six liver
      transplant recipients (18 with chronic rejection and 48 with normal graft
      function) and 38 controls (23 healthy volunteers and fifteen patients with
      biliary duct stricture) were studied with in vivo (31)P-MRS. All the data and
      peak values were calibrated and calculated by the software of spectroscopy
      analysis GE, and the pH values were calculated by the Malloy's formula, then the
      peak area ratios and altitudes of metabolites relative to adenosine triphosphate
      (beta-ATP)and phosphate (Pi) were measured. RESULTS: (a) The peak area ratios and
      altitudes of PME and PDE in biliary duct stricture group and chronic rejection
      group were higher than those of healthy volunteer group and normal graft function
      group. Patients with chronic rejection had significant differences in the peak
      area ratios of PME: beta-ATP (P < 0.05) and PDE: beta-ATP (P < 0.05) and in the
      altitudes of PME: beta-ATP (P < 0.05) as compared with the other groups. (b) The
      ratios of beta-ATP/Pi decreased in biliary duct stricture group, while they
      increased in chronic rejection group. There was no difference between the four
      groups. There were similar changes in the ratios of PME/Pi, but there was
      significant difference between the chronic rejection group and the other three
      groups. (c) pH values increased in biliary duct stricture group and chronic
      rejection group, though the difference was not significant with the healthy
      control group. (d) Histological specimens showed focal loss of hepatocytes,
      degeneration, and hepatocytic atrophy. CONCLUSIONS: (31)P-MRS imaging is valuable
      in detecting the metabolism of the liver after transplantation, and suggests that
      further investigation of alterations in the phospholipid metabolism may be a
      useful future direction of research.

PMID- 23166919
TI  - Uganda battles Marburg fever outbreak.

PMID- 23166920
TI  - US health reform still faces challenges.

PMID- 23166921
TI  - Europe gives gene therapy the green light.

PMID- 23166922
TI  - A secret history.

PMID- 23166923
TI  - microRNAs in colon cancer: a roadmap for discovery.
AB  - Cancer omics data are exponentially created and associated with clinical
      variables, and important findings can be extracted based on bioinformatics
      approaches which can then be experimentally validated. Many of these findings are
      related to a specific class of non-coding RNA molecules called microRNAs (miRNAs)
      (post-transcriptional regulators of mRNA expression). The related research field
      is quite heterogeneous and bioinformaticians, clinicians, statisticians and
      biologists, as well as data miners and engineers collaborate to cure stored data
      and on new impulses coming from the output of the latest Next Generation
      Sequencing technologies. Here we review the main research findings on miRNA of
      the first 10 years in colon cancer research with an emphasis on possible uses in
      clinical practice. This review intends to provide a road map in the jungle of
      publications of miRNA in colorectal cancer, focusing on data availability and new
      ways to generate biologically relevant information out of these huge amounts of
      data.

PMID- 23166924
TI  - Conformational transition of the lid helix covering the protease active site is
      essential for the ATP-dependent protease activity of FtsH.
AB  - When bound to ADP, ATP-dependent protease FtsH subunits adopt either an "open" or
      "closed" conformation. In the open state, the protease catalytic site is located
      in a narrow space covered by a lidlike helix. This space disappears in the closed
      form because the lid helix bends at Gly448. Here, we replaced Gly448 with various
      residues that stabilize helices. Most mutants retained low ATPase activity and
      bound to the substrate protein, but lost protease activity. However, a mutant
      proline substitution lost both activities. Our study shows that the
      conformational transition of the lid helix is essential for the function of FtsH.

PMID- 23166925
TI  - [Is there an optimal variant of the gastroenteroanastomosis after the distal
      subtotal gastric resection?].

PMID- 23166926
TI  - Mechanisms for preferential dopaminergic cell loss induced by alpha-synuclein.

PMID- 23166927
TI  - An important step towards translation of stem cell therapies in clinical
      applications for neurodegenerative diseases and beyond?

PMID- 23166928
TI  - Oligodendroglial dysfunction associated with lactate transport deficiency
      contributes to neurodegeneration.

PMID- 23166929
TI  - Dems step it up. Reform law gets big pre-election push.

PMID- 23166930
TI  - Largest healthcare real estate investment trusts. Publicly traded healthcare
      REITs ranked by market capitalization, as of July 31.

PMID- 23166931
TI  - It's Dems turn at bat. After listening to days of reform bashing, expect
      loyalists to fight back hard.

PMID- 23166932
TI  - Speaking out against reform. GOP leaders emphasize the need to repeal ACA.

PMID- 23166933
TI  - Largest healthcare management consulting firms. Ranked by total 2011 provider
      revenue ($ in millions).

PMID- 23166934
TI  - Doing the math. Groups say the debt-ceiling law's $11.1 billion hit to Medicare
      would lead to mass layoffs in healthcare.
AB  - As Washington wrestles with looming mandatory cuts forced by a deficit agreement,
      the AMA, AHA and ANA are warning of massive job cuts. "If I've got a choice of
      maintaining these beneficial programs or contract them for my core mission,
      you're going to choose your core mission. And that will cost the community more
      in terms of health and of dollars," says Rich Morrison, of Adventist Health
      System.

PMID- 23166936
TI  - Award of Excellence/Built: UC San Diego Health System's Sulpizio Cardiovascular
      Center, La Jolla, Calif.

PMID- 23166935
TI  - Consumer savings. HHS report: ACA provisions saved $2.1 billion.

PMID- 23166937
TI  - Award of Excellence/Built: Vivian and Seymour Milstein Family Heart Center, New
      York-Presbyterian Hospital/Columbia University Medical Center, New York.

PMID- 23166938
TI  - Largest allopathic medical schools. Ranked by total active enrollment for the
      2011-12 school year.

PMID- 23166939
TI  - Largest osteopathic medical schools. Ranked by total active enrollment for the
      2011-12 school year.

PMID- 23166940
TI  - Seeking direction. Government pressed for health-exchange details.

PMID- 23166941
TI  - Largest physician staffing firms. Based on NAPR membership, ranked by number of
      physician recruiters as of September 2012.

PMID- 23166942
TI  - Regs sought on exchanges.

PMID- 23166943
TI  - Largest medical home practices. Ranked by total number of patient visits enrolled
      in 2011.

PMID- 23166944
TI  - Physician disciplinary actions by state. Ranked by total board actions in 2011.

PMID- 23166945
TI  - A political scrum. Post-election battles shaping over healthcare costs.

PMID- 23166946
TI  - Healthcare's hottest: recognizing 40 of the fastest-growing healthcare companies.

PMID- 23166947
TI  - 2012 up & comers. Recognizing 12 rising stars who represent the next generation
      in healthcare leadership.

PMID- 23166948
TI  - Largest healthcare law firms. Based on a blended score of healthcare lawyers
      employed in 2011 and AHLA membership as of July 27.

PMID- 23166949
TI  - Taking stock of exchanges. Size of coverage is among the battles that states
      face.

PMID- 23166950
TI  - The homestretch. With a month to go in presidental race, provider groups weigh
      what's at stake in the election aftermath.

PMID- 23166952
TI  - Largest PAC donations from groups representing health professionals. Ranked by
      total political action committee contributions to federal candidates for 2012
      election cycle.

PMID- 23166951
TI  - Still seeking parity. Behavioral health providers back bill on IT funding.

PMID- 23166953
TI  - Among the best at heart.

PMID- 23166968
TI  - Research shows that blood pressure targets need individual attention.  In
      general, lower is better, but some patients can tolerate a blood pressure that is
      higher than recommended levels.  Patients with diabetes should be especially
      careful.

PMID- 23166969
TI  - Research: drug-eluting stents as safe as bare metal stents. Factors such as the
      size of the affected artery and the patient's medical history help determine
      which type of use.

PMID- 23166970
TI  - Fenofibrates get a second look.  Research shows popular drugs fail to lower
      cardiovascular risk for most patients already taking a statin.

PMID- 23166971
TI  - What you should know about statin side effects.  The benefits of these drugs far
      outweigh the risks.

PMID- 23166972
TI  - Imaging tests can lead to harmful radiation exposure. Tests designed to diagnose
      heart problems may increase your cancer risk.

PMID- 23166973
TI  - Staying social may control hypertension.  Research shows that feelings of
      loneliness can contribute to high blood pressure.

PMID- 23166974
TI  - I read recently that sleep apnea can raise the risk of stroke.  I knew it
      affected blood pressure, but what is this stroke risk, and is there still a high
      risk even if you're using a CPAP machine?  I'm especially concerned because my
      father had a stroke when he was just 67 and I'm 61 now.

PMID- 23166975
TI  - I was diagnosed with hypothyroidism several years ago, and have heard that it can
      have an effect on heart health.  I recently started taking a blood pressure
      medication and am worried how my thyroid disease might complicate my
      cardiovascular health.  Are there any special precautions I should be taking, and
      will the medications I take interact?

PMID- 23166976
TI  - Clarification and apology.

PMID- 23166977
TI  - The main facts of Moll's life are quickly told. Introduction.

PMID- 23166978
TI  - Commander's introduction.

PMID- 23166979
TI  - [Expert answer. Coronary artery patients with atrial fibrillation on
      anticoagulation treatment may need antithrombotic treatment. What kind is
      there?].

PMID- 23166981
TI  - [The relevance of C. G. Jung's work].

PMID- 23166982
TI  - [The resolution of the XXVI (89th) session of the RAMS General Meeting
      ("Neurological Sciences in modern medicine: neurophysiology, neurobiology,
      neurology, neurosurgery, psychiatry"].

PMID- 23166983
TI  - [Modern neuroendocrinology].

PMID- 23166984
TI  - [Advance of genetics and genomics in neurology].
AB  - Studies of genomic background of neurological disorders are very actual in view
      of their high population prevalence, severe course, serious impact on patients'
      disability and progressive mental and physical de-adaptation. In the paper,
      problems of genetic heterogeneity of hereditary neurological disorders and
      character of the respective genetic burden in the regions of Russian Federation
      are discussed in detail, a 'dynamic' type of mutations (increase in number of
      microsatellite repeats copies) attributable to many neurodegenerative diseases is
      analyzed, and achievements of Russian researchers in the identification of genes
      for hereditary neurological disorders and in the realization of pilot protocols
      of gene therapy are presented. Problems related to studies of genetic
      predisposition to common multifactorial diseases of the nervous system are
      discussed.

PMID- 23166985
TI  - [Intracellular brain regeneration: a new view].
AB  - Mechanism of neuron regeneration in the cortex was discovered. Heterokaryon, a
      cell with two distinct nuclei, is formed by the fusion of neuron with
      oligodendrocyte. We showed that oligodendrocyte nucleus in heterokaryons is
      exposed to neuron-specific reprogramming. Oligodendrocyte nucleus becomes similar
      to neuron nucleus and in result of reprogramming is undefined from it according
      to morphology (size, shape, chromatin structure). Reprogrammed oligodendrocyte
      nuclei begin to express the neural specific markers NeuN and MAP2. Rate of
      transcription in the oligodendrocyte nuclei increases as in neurons. After
      completion of neuron-specific reprogrammin, second nucleus appears in neuron
      which increases the functional capacity of the cell. We present evidence that
      this process is the basis of physiological and reparative regeneration of the
      brain.

PMID- 23166986
TI  - [Ontogenesis of neurocognitive development of children and adolescents].
AB  - The article represents the results of neurocognitive development study in
      progress. Clinical methods of investigation are supplemented with examination of
      children with Russian computer psychophysiological complex "Psichomat", which
      allows to examine a number of cognitive functions--perception, attention, memory,
      visual-motor coordination, processes of analysis and synthesis--in mathematical
      function expression: milliseconds and percentage of mistakes. A child's
      intrauterine and postnatal development is determined by various factors.
      Cognitive processes, which are ascending accordingly to a child's age, play
      significant role in social development. The standard charts of children
      psychoneurological development, worked out by the authors, must become key
      factors both for pediatricians of different subspecialities and for parents and
      psychologists, in order not to miss the beginning of some pathology condition-
      from development delay to retardation. During the analysis of cognitive status of
      a child, speech development, behavior and emotions should be assessed. The
      deficiency of cognitive functions causes difficulties in education and contact
      with a child, which in some cases leads to formation of syndromal pathological
      conditions and disease entities (from mild development delays to different stages
      of oligophrenia). It is necessary to educate pediatricians of various
      subspecialities and pediatric neurologists the methods of children examination in
      order to determine the "cognitive profile" according to the age, health
      condition, presence of somatic and/or psychoneurological diseases and influence
      of the drug therapy both on a child's organism and cognitive processes.

PMID- 23166987
TI  - [Vladimir Mikhailovich Bekhterev--the founder of the clinical neuropsychiatry].
AB  - The article presents main milestones in the career of Vladimir Mikhailovitch
      Bekhterev. The research in anatomy and physiology of the brain performed by V.M.
      Bekhterev gave original data of worldwide priority. V.M. Bekhterev significantly
      improved methodology of neurological examination and differential diagnosis in
      clinical neuropsychiatry. The scientific heritage of V.M. Bekhterev proves his
      outstanding role in establishment and development of the neuropsychiatry.

PMID- 23166988
TI  - [The early embryonal anomalies of human brain].
AB  - The mechanisms of early embryonic pathology of the brain in man and animals were
      studied. Analysis of the biomechanical properties of development of nervous
      tissue and embryonal experiments demonstsrated that tangential neuroepithelial
      intention is the major source of positional information. Experimental changes in
      the neuroepithelial intention system resulted in various types of embryonal
      anomalies of the nervous system. Mechanical-dependent ion channels that have
      marked periods of sensitivity and determine the histogenetic direction of
      neuroblast cell differentiation were found to underline the mechanosensitivity of
      the neuroepithelium. Experimental findings were compared with unique autopsy data
      on early development of the human brain. Human embryos were examined from
      neurulation to month 6 of development. Different types of human embryonal brain
      anomalies were shown to occur with 3 types of neurulation disordes: 1) an open
      preneuropore is responsible for anomalies of the forebrain and etmoidal area; 2)
      arrested neurulation in the postneuropore leads to anomalies of the
      diencephalons, midbrain, and occipital region; 3) impaired neurulatuion in the
      caudal region is a cause of spinal cord anomalies. The above anomalies resulted
      from local compensatory responses of the neuroepithelium due to the lack of
      intentions that are characteristic of normal development of the neural tube.

PMID- 23166989
TI  - [From I.P. Pavlov to contemporary neurosciences].

PMID- 23166990
TI  - [The informative mechanisms of systemic organization of psychic activity].
AB  - In this review on the basis of functional systems theory developed by P. Anokhin
      theoretical approaches to informative mechanisms of systemic organization of
      psychic activity are presented. Author formulates the conception on discrete
      system quantums of psychic and behavioral activity from needs to its satisfaction
      and develops its informative equivalents. It was shown that informative
      equivalents of needs and its satisfaction are reflected in structures of action
      acceptors in the form of dynamic informative images. On the basis of acceptors of
      results of action informative systemic quantums are developed which constantly
      control its manifestation in behavioral systemic quantums. Informative systemic
      quantums are extracted in advance by predominate motivations and are associated
      with negative emotions of needs and positive emotions of their satisfaction. The
      content of this review confirms I.P. Pavlov's foresight on possible confluence of
      material and idealistic processes in psychic human activity.

PMID- 23166991
TI  - [Neurology at the border of centuries: achievements and prospects].
AB  - A significant role of neurology for medicine and society is caused by severity of
      clinical presentations and consequences of the nervous system diseases, as well
      as by huge economic burden related to neurological pathology. The paper presents
      a review of the current state and prospects for the development of socially most
      important fields of modern neurology, among which one can list studies of
      cerebrovascular, neurodegenerative, demyelinating and hereditary disorders,
      discovery of molecular mechanisms of their pathogenesis, and improvement of the
      methods of treatment, neurorehabilitation and prophylaxis on the basis of new
      medical technologies. An essential link between clinical and basic research in
      expanding the existing knowledge about the structure/functions of the brain in
      normal conditions and different-type pathological processes is stressed.

PMID- 23166992
TI  - [Fundamental and applied aspects of the hematoencephalic barrier research].
AB  - The results of fundamental and applied studies of blood-brain barrier had been
      conducted by authors during the last 10 years are summarized in the publication.
      The molecular anatomy of barrier microvessels, as well as promising markers of
      BBB and other proteins involved in barrier functions are discussed. Via in vitro
      experiments with endothelial cells of cerebral microvessels we characterized the
      basic conditions required for adequate BBB modeling. The in vivo data of BBB
      permeability for macromolecules in normal and different pathological process is
      including radiation injury, hyperosmotic shock, and nervous tissue ischemia are
      properly described. A particular attention was focused upon the experimental
      studies of the permeability and functional reorganization of barrier endothelium
      during tumor neoangiogenesis. We detected a dramatically increased permeability
      of neoplastic microvessels both for horseradish peroxidase/serum albumin and
      labeled monoclonal antibodies. The increased tumor permeability for IgG and the
      overexpression of target antigens in tumor tissue and peritumoral zone make
      possible the targeted delivery of diagnostics and therapeutic agents into the
      tumor by means of monoclonal antibodies.

PMID- 23166994
TI  - Infection prevention.

PMID- 23166993
TI  - The dental savings account. Putting the dentist and the patient back in control.

PMID- 23166995
TI  - Simple steps to protect your online reputation.

PMID- 23166996
TI  - Your virtual filing cabinet.

PMID- 23166997
TI  - Diagnostic discussion. Histoplasmosis.

PMID- 23166998
TI  - Anticoagulant therapy and dentistry.

PMID- 23166999
TI  - FDAS--your health care reform resource.

PMID- 23167000
TI  - A comparative evaluation of the healing ability of bilateral periapical lesions
      treated with and without the use of platelet-rich fibrin.
AB  - Periradicular surgery aims to achieve complete wound healing and regeneration of
      the periodontal unit. Platelet-rich fibrin (PRF) is a platelet concentrate that
      is widely used to promote tissue healing and bone induction through its various
      growth factors and has been used in this study. This case report describes the
      use of PRF unilaterally in a bilateral periapical lesion in the same patient. The
      site treated with PRF showed better healing than the other site. This was
      confirmed with a 3-D X-ray.

PMID- 23167001
TI  - Dental hygiene economics. Coping with the supply and dental issues of dental
      hygiene.

PMID- 23167002
TI  - AAOMR position paper lacks foundation, harmful to dental profession.

PMID- 23167004
TI  - Inspiration for pursuing excellence.

PMID- 23167003
TI  - Using the best tool for the job.

PMID- 23167005
TI  - Compulsory cycle helmets.

PMID- 23167006
TI  - Providing comfort and support to older people.
AB  - This article reports on a scheme run by Age UK at Hillingdon Hospital, Middlesex,
      to help support emergency department (ED) staff with the care of older people.
      The A&E support-worker team assists patients with non-clinical activities, such
      as going to the toilet, eating meals and finding out care-related information.
      The support-worker scheme has been running for nine years and its success has
      prompted Age UK to consider expanding it nationally. It comes at a time when
      there is a growing focus on the care Solder patients receive in hospitals.

PMID- 23167007
TI  - Caring for people who have intellectual disabilities.

PMID- 23167008
TI  - Intermediate care for homeless people: results of a pilot project.
AB  - A year-long, nurse-led intermediate care pilot project was undertaken at a 120
      bed homeless hostel in south London to improve healthcare outcomes among the
      clients involved, and to reduce emergency department (ED) attendance, ambulance
      call outs and use of acute care services. By the end of the year, the number of
      ED and hospital admissions had dropped significantly. The project was recognised
      by the Department of Health in 2010 as an example of innovative practice in work
      with 'at-risk' groups, and was awarded the 2011 Nursing Standard Community
      Nursing Award. This article considers reasons for the success of the project and
      the lessons that can be learned from it.

PMID- 23167009
TI  - Acute supraventricular tachycardia in children.
AB  - This article describes the management in emergency departments of
      supraventricular tachycardia (SVT) in children. Of all forms of symptomatic
      arrhythmia in infants, children and adolescents, SVT is the most common. Its
      clinical presentation varies with the child's age, and it can be difficult to
      diagnose in infants and young children. It is important that the nurses in the
      emergency department consider a diagnosis of SVT in young children with histories
      of poor feeding, lethargy, irritability, excessive sweating or pallor (Zeigler
      1994) and in older children with histories of palpitations, dizziness, chest
      pain, syncope or shortness of breath (Uzun 2010). If SVT is suspected, a 12-lead
      electrocardiogram should be recorded. Vagal manoeuvre may be successful but in
      some cases intravenous adenosine is necessary. Children with Wolff-Parkinson
      White syndrome are at risk of sudden cardiac death associated with SVT, and
      should not be treated with calcium channel blockers or digoxin.

PMID- 23167010
TI  - Overcoming language barriers when teaching interprofessional groups.
AB  - The author of this article undertook a small qualitative study of the best way to
      prepare unscheduled care staff for team-based delivery of patient care. The study
      was intended to highlight problems in interprofessional training courses so that
      guidelines for the delivery of such courses can be developed. The findings show
      that trainers cannot assume that all participants in training courses understand
      the terminology used. This article discusses this finding further.

PMID- 23167011
TI  - Early warnings needed for young.

PMID- 23167012
TI  - Tuning into young people's perspectives on sexual health.

PMID- 23167013
TI  - Importance of school nurses' role promoted by government initiative.

PMID- 23167014
TI  - The impact of paediatric early warning systems.
AB  - The child who is ill enough to be admitted to a children's ward has the potential
      to deteriorate rapidly. If this deterioration is not recognised and acted on in a
      timely manner, such children may require cardiopulmonary resuscitation, high
      dependency or intensive care. A paediatric early warning tool used with routine
      nursing observations will alert staff to the need for increased monitoring, the
      support of an associated outreach team or emergency medical attention. If the
      tool is used, a nurse can provide objective, transparent evidence of the child's
      condition to experienced clinicians. Appropriate education and supervision of
      staff should be ensured through the use of an outreach team.

PMID- 23167015
TI  - A review of extracorporeal membrane oxygenation in the UK.
AB  - Extracorporeal membrane oxygenation (ECMO) is needed for a small number of sick
      infants, children and adults who fail to respond to maximum ventilator therapy
      and pharmacological support. As the technology continues to develop, indications
      for early treatment with ECMO increase and the prognosis improves. Admission to a
      specialist unit is required during therapy, but essential intensive care needs
      remain as they would for any critically ill child. Attentive communication with,
      and support for, families are more important than ever. The publication of this
      article was delayed until after the announcement of the NHS Safe and Sustainable
      review of children's cardiac surgical services in the UK.

PMID- 23167016
TI  - Respite care in seven families with children with complex care needs.
AB  - AIM: To evaluate the experience of nursing respite care in families caring for
      children with complex health needs. METHOD: Seven mothers took part in semi
      structured, in-depth interviews, which were taped, transcribed and coded. Results
      were categorised thematically. FINDINGS: Families described a positive impact on
      all aspects of life, the high value of respite care and the preference for more
      information, flexibility, choice and co-ordination of the different services.
      CONCLUSION: Respite care is highly beneficial to family life, but there need to
      be clearer communication lines and a stable, flexible and adequately resourced
      workforce. Families value a single point of contact and would prefer more respite
      care to be available.

PMID- 23167017
TI  - Clinical assessment and management of a child with bronchiolitis.
AB  - Children's nurses frequently encounter children who have bronchiolitis and the
      severity of the illness can vary from mild to severe. This article is designed to
      enable children's nurses to understand the pathophysiology of the illness and how
      to provide a high quality of care. The article aims to enhance the reader's
      clinical assessment and management of a child with bronchiolitis. There are also
      suggestions on maintaining and enhancing family-centred care and improving ward
      practice with strict barrier nursing procedures.

PMID- 23167018
TI  - Healthcare becoming most critical issue in 2012 presidential election.

PMID- 23167019
TI  - Eight reasons your practice can't afford a lunch break.
AB  - Keeping phone lines open through the mid-day hours may seem commonplace to many
      practices; however, there are still some that close down entirely during these
      important hours when patient needs and potential new patient calls don't take a
      lunch break. This article addresses how many practices violate the best practice
      of keeping phone lines open throughout business hours while discussing the impact
      to your practice, helping you understand the real cost of hanging on to this old
      school thinking, such as decreased staff efficiency, reduced customer service
      during prime hours, a compromised image, delayed medical care, and the loss of
      potential new patients. This article also provides suggestions on how to
      implement this important phone coverage in your practice and the reasons it's
      imperative that you do.

PMID- 23167020
TI  - The reinvented medical practice: eight entrepreneurial ideas to generate more
      revenue, professional rewards, and fun.
AB  - Would you like more control over your financial destiny? Here are eight
      entrepreneurial ideas to accelerate your practice's growth and help your practice
      thrive--no matter what happens with the economic recovery or healthcare reform.

PMID- 23167021
TI  - What to do before the office for civil rights comes knocking: Part II. Coping
      with breaches, enforcement, and other fallout of HIPAA: the significance of harm.
AB  - Physicians and their lawyers must review business associates that are subject to
      HIPAA and must revisit their HIPAA privacy and security efforts to comply with
      the new rules. In particular, they must: (1) review and revise their HIPAA
      privacy and security notices, policies, administrative materials, and training
      manuals; (2) review, negotiate, and revise their business associate agreements;
      and (3) train any employees who have access to PHI with respect to the changes to
      HIPAA's rules as a result of ARRA.

PMID- 23167022
TI  - E-health blood pressure control program.
AB  - Both technological and human factors design requirements for integration of home
      blood pressure monitoring (HBPM) into a patient centered medical home (PCMH)
      model primary care practice are described. Patients with uncontrolled
      hypertension were given home blood pressure (BP) monitors, and after a three
      month run-in period introduced to either a high-tech only (HBPM connectivity to
      personal health record and tailored Web portal access) or a high-tech/"high
      touch" (high-tech solution plus patient navigator [PN]) solution. Features of the
      Web portal included: BP graphing function, traffic-light feedback system of BP
      goal attainment, economic incentives for self-monitoring, and dual patient-facing
      and care-team-facing dashboard functions. The e-health BP control system with PN
      support was well received by patients, providers, and the healthcare team.
      Current e-health technology and limited technological literacy of many patients
      suggest that a PN or some other personnel resource may be required for the
      adoption of patient-facing technology in primary care.

PMID- 23167023
TI  - Be prepared in the post-PPACA liability and healthcare environment: assure, do
      not assume.

PMID- 23167024
TI  - Mastering energy to avoid drama in your healthcare practice.
AB  - Energy takes on many meanings depending on the context, but for the purposes of
      the workplace, I refer to energy as the force that serves to either propel us to
      greater purposes or destroy us with our drama. As it relates to the healthcare
      setting, our energy can help us serve our patients well, manage our staff with
      utmost clarity and civility, and nurture an environment of impeccable customer
      service. Or if not mastered properly, it can trigger workplace bullying,
      disruptive behavior, physical burnout, or, in short-drama. With literally
      hundreds of scientific studies, white papers, and expert reports on how fatigue
      leads to serious accidents and death, it seems we are still in denial about the
      impact of fatigue on patient safety and employee safety and well-being. Before we
      can address drama issues, we must first make a commitment to support policies and
      a culture that preserves the physical energy of those we manage.

PMID- 23167025
TI  - Data envelopment analysis: dynamic possibilities in an academic medical center
      application.
AB  - In a fairly short period of time, data envelopment analysis (DEA) has grown into
      a powerful quantitative, analytical tool for measuring the relative performance
      of similar organizations. DEA has been successfully applied to traditional
      service industries such as universities and hospitals as well as to trades as
      diverse as banking and manufacturing. To the best of our knowledge, however, DEA
      has not been applied in the academic medicine healthcare setting. This paper
      discusses fundamental DEA models and some of their extensions, the arena into
      which we introduced DEA, and an example from our own institution exploring how
      DEA can advance the value proposition within an academic healthcare organization.

PMID- 23167026
TI  - Let your communication skills equal your clinical skills.
AB  - Relating effectively with patients is among the most valued skills of clinical
      care. Honing your communication skills is an art that every physician needs to
      learn and understand. In this era of increased volume of patients there is a
      tendency to lose sight of the importance of having good communication skills.
      This article will review 11 suggestions for letting your communication skills
      equal your clinical skills.

PMID- 23167027
TI  - M-health: the union of technology and healthcare regulations.
AB  - As healthcare continues to become technology-based, so too does the potential for
      increased governmental regulation of mobile health (m-health). "M-health" is a
      broad term that applies to hardware or software that is mobile and delivers
      healthcare wirelessly. M-health includes consumer- and provider-oriented medical
      applications (apps), such as weight monitoring apps, and medical devices, such as
      glucose meters, that send health information back to the provider. It is
      important for anyone entering the field of mobile healthcare, whether developing
      apps, providing remote medical care, or simply investing in the future of
      healthcare technology, to understand the impact governmental oversight can have
      on this industry. Understanding the different roles to be played by the federal
      and state governments can be the difference between success and frustration.

PMID- 23167028
TI  - Facing the truth: knowing the score.

PMID- 23167029
TI  - Keeping up with ICD-10: will the extension stick?
AB  - The idea of keeping up with ICD-10 has had its ups and downs amid rumors of
      extensions and even skipping it to go directly to ICD-11. It is beginning to feel
      like a rollercoaster ride. With the recent implementation deadline extended by
      the Department of Health and Human Services to October 2014, all healthcare
      providers should be continuing with their ICD-10 implementation planning. This
      article will discuss the ICD-10 transition and includes steps to get to
      implementation compliance.

PMID- 23167030
TI  - How to be a better team player: fifty strategies.
AB  - Many medical practice employees have become skeptical of the phrase be a team
      player and with good reason. Too often the phrase means simply to keep your mouth
      shut and to go along with what everyone else wants. However, being a team player
      has real meaning and value, and it doesn't mean that you must knuckle under to
      pressure. This article suggests 50 strategies that will help you become a better
      team player in your medical practice. It explores ways for you to manage your
      emotions and to translate them into effective and strategic communication. It
      teaches you how to read the emotions of your teammates and to listen actively to
      what they say. Most of all, this article will help you develop a team attitude
      and live that attitude every day in your medical practice through your behaviors.
      This article is laced with more than a half-dozen action tips. It includes a
      description of the most pervasive, destructive, and selfish team roles that you
      will want to avoid. It offers a clear description of the difference between a
      group and a team. Finally, this article includes five fun and effective team
      building exercises for you to use in your medical practice to boost morale,
      improve your effectiveness, and strengthen your medical practice team.

PMID- 23167031
TI  - The business side of healthcare practice: retooling graduate medical students
      through medical school curriculum enhancements.
AB  - Practicing physicians often complain that medical schools failed to provide them
      with any substantive business training. And with the financial stress placed on
      today's medical practices, doctors feel unprepared for the rigors of managing a
      business and shortchanged when it comes to cashing-in on the fair value of their
      education. The University of South Florida piloted a three-credit course for
      nonbusiness-minded graduate students, aptly named "The Business Side of
      Medicine." The intent was to imprint aspiring, time-constrained graduate
      students, early in their biomedical education, with the need to develop a sound
      business acumen. Students, if made aware that the structure of healthcare
      practice is changing into a value-based and consumer-driven marketplace, will
      process in tandem with their graduate and medical schooling the notion that
      wellness and compensation are interdependent. The Business Side of Medicine
      addresses four core concepts that will logically germinate within the students'
      minds the desire to make practical, profitable career choices.

PMID- 23167032
TI  - Partnering with universities and colleges to facilitate the PCMH process. An
      innovative plan to place healthcare management students into practices to promote
      healthcare transformation.
AB  - Practices contemplating the Patient-Centered Medical Home recognition process are
      confronted with an arduous task. Perhaps the most palpable constraints are time
      management combined with staff allocation decisions. Outside consultants can be
      expensive and disruptive to practice flow. Collaborating with a local college or
      university's healthcare management or other health career students might be one
      answer. This article will explore that option.

PMID- 23167033
TI  - Using RVUs to analyze and improve your medical group.

PMID- 23167034
TI  - The most common patient complaints that the front office receives and how to
      manage them.
AB  - Every practice has issues with patients, and one of the most common contact
      points is between the patient and the receptionist. This contact point requires a
      receptionist capable of managing the patient and turning a negative into a
      positive. It also requires tact and diplomacy so that the patient is not
      embarrassed or placed on the defensive. This article will present 10 of the most
      common complaints that the receptionist is likely to receive and how to
      effectively manage and diffuse each of the issues.

PMID- 23167035
TI  - Prioritization for the practice and physician.
AB  - The physician and practice manager have much on their plate on a day-to-day
      basis. The issue then becomes what does not get accomplished today hopefully will
      be taken care of tomorrow, or the next day, or next week. Unfortunately, those
      two- to three-minute projects never seem to get accomplished; and just when you
      think you have time, you don't. Worse yet, the list of to do's continues to grow,
      making the day more stressful. Yet there are solutions to these issues, which
      involve just a bit of prioritization, time management, and organizational skills.
      This article addresses the most common problems for doctors, practice managers,
      and staff and includes practical advice, information, and resources to help
      decrease stress and increase time.

PMID- 23167036
TI  - Commonsense approach to ICD-10 implementation.

PMID- 23167037
TI  - Are you using social media to build your practice? Patient trends and healthcare
      changes give new value to online presence.
AB  - Social media is an effective, efficient tool for physicians to use to grow their
      practices, network, and distribute information to large groups of people. While
      87% of physicians use social media in their personal lives--everything from
      Facebook, to Twitter, to blogs and YouTube--only 26% use two or more sites for
      connecting professionally. What an opportunity they're missing! Healthcare
      professionals, in particular, must heed a few words of warning, but beyond that,
      there are some proven tricks for developing a respected, charismatic online
      presence.

PMID- 23167038
TI  - Computer briefs: big data.

PMID- 23167039
TI  - Why the Supreme Court race is important.

PMID- 23167040
TI  - Philosophy matters.

PMID- 23167041
TI  - The effect of payment reform on physician practices. Part 1. The shift from fee
      for-service to outcomes-based reimbursement.

PMID- 23167042
TI  - Don't get too comfortable, stage 2 meaningful use requirements have arrived.

PMID- 23167043
TI  - Recommendations for the management of HBV-infected health care providers.

PMID- 23167044
TI  - As the seasons change....

PMID- 23167045
TI  - Hemodialysis and toxins: is there a risk?

PMID- 23167046
TI  - Self-management support for peritoneal dialysis patients.
AB  - The increasing prevalence of chronic illnesses and kidney disease, in particular,
      makes it necessary to adopt new approaches towards their management (Wagner,
      1998). Evidence suggests that promoting self-management improves the health
      status of peritoneal dialysis (PD) patients, as they manage upwards of 90% of
      their own care. Patients who are unable to self-manage suffer from various
      complications. This project proposes an intervention aimed at improving self
      management skills among PD patients. GOAL: To promote self-management in
      peritoneal dialysis patients. This is achieved through the following objectives:
      (a) develop an algorithm that can improve patients' ability to solve the specific
      problem of fluid balance maintenance, (b) develop an educational session for
      patients on how to use the algorithm, and (c) develop an implementation strategy
      in collaboration with the PD nurse. METHOD AND RESULTS: Three measures evaluate
      the effectiveness of the intervention. First, a telephone call log shows that
      participating patients call the clinic less to inquire about fluid balance
      maintenance. Next, a pre- and post-intervention knowledge test measures definite
      knowledge increase. Finally, a Patient Satisfaction Questionnaire reveals overall
      satisfaction with the intervention. CONCLUSION: This project, which proved
      beneficial to our patient population, could be duplicated in other clinics. The
      algorithm "How do I choose a dialysis bag" and the slides of the educational
      sessions can be shared with PD nurses across the country for the benefit of PD
      patients.

PMID- 23167047
TI  - The community health promotion plan: a CKD prevention and management strategy.
AB  - Chronic kidney disease (CKD) is one of the top 10 causes of death. CKD is often
      caused by diabetes mellitus (DM) and hypertension (HTN). Both DM Type 2 and HTN
      are treatable and preventable and, yet, the population of individuals diagnosed
      with these two diseases is increasing. Millions of dollars are spent every year
      providing dialysis treatments for patients with CKD. This money only accounts for
      dialysis and does not include the millions spent on complications such as
      infections, medications, tests and procedures. The burden to society is
      tremendous and the quality of life for these people is often poor. Health
      promotion and early detection is a key factor in reducing the risk for and
      incidence of DM and HTN, thus reducing the incidence of CKD. Three-quarters of
      health problems are preventable. Educating and providing the community with
      resources about diet, exercise, regular physical examinations, medication, and
      smoking cessation can empower the population with the necessary knowledge to help
      prevent these diseases. Health promotion and access to health promotion
      activities can, therefore, provide an active and healthier life.

PMID- 23167048
TI  - Management of depression in hemodialysis patients.

PMID- 23167049
TI  - Establishing a successful intradialytic exercise program: Part 1.

PMID- 23167050
TI  - Does one medical school's admission policy help a rural state "grow their own"
      physicians?
AB  - CONTEXT: The University of Mississippi Medical Center (UMC) has been the only
      medical school in the state since its inception in 1955 (until the 2008
      establishment of the William Carey College of Osteopathic Medicine, yet to
      graduate its first class). Recruiting out-of-state physicians is difficult in
      Mississippi, and stakeholders frequently talk of "growing our own" physicians,
      especially challenging with a single public medical school. PURPOSE: This study
      investigates: (1) the proportion of a recent (1990-1999) cohort of UMC graduates
      practicing in Mississippi, (2) the proportion of all practicing Mississippi
      physicians who are UMC grads, (3) whether UMC graduates are more likely to
      practice in rural, small towns, or geographically isolated areas than other
      physicians, and (4) whether UMC graduates are more likely to recommend
      Mississippi as a practice location to new medical school graduates. METHODS:
      Using Mississippi Board of Medical Licensure data (2009) and Mississippi Medical
      Doctors survey data (2007-2008), we employ GIS, logistic regression, and
      multinomial logistic regression models. We also use qualitative methods to
      examine interviews from purposefully sampled minority and/or female Mississippi
      physicians from the Mississippi Medical Doctors survey. FINDINGS: Approximately
      56% of UMC 1990-1999 cohort grads are practicing in Mississippi. Moreover, UMC
      graduates--of any year--constitute about 58% of Mississippi's practicing
      physicians. UMC graduates are not more likely to practice in rural, small towns,
      or geographically isolated areas in Mississippi than physicians who graduated
      elsewhere. Controlling for other factors, UMC grads are not more likely to
      recommend practicing in Mississippi than physicians trained elsewhere.
      CONCLUSION: Health educators and policy makers should consider broadening UMC's
      enrollment policies, and greater emphasis should be placed on recruiting
      physicians.

PMID- 23167051
TI  - Top 10 facts you should know about headaches.

PMID- 23167052
TI  - Just off the press--info you want to know: probiotics--are they beneficial?

PMID- 23167053
TI  - Do the Supreme Court elections really matter?

PMID- 23167054
TI  - 401(k) changes will help physicians better understand their practice retirement
      plans.

PMID- 23167055
TI  - "It's time to change the culture of the NHS".

PMID- 23167056
TI  - "Boost patient outcomes by giving nurses the time to care".

PMID- 23167057
TI  - "If we care enough, we can teach people how to be compassionate".

PMID- 23167058
TI  - "Understanding the Liverpool Care Pathway is essential".

PMID- 23167059
TI  - How to ensure patient safety drug dose caculation.

PMID- 23167060
TI  - How accurate are X-rays to check NG tube positioning?
AB  - The position of a nasogastric tube is vitally important for patients' safety and
      wellbeing. X-rays are sometimes used to determine whether nasogastric tubes are
      correctly positioned, but how effective are they? To find out, we undertook an
      audit of data from the radiology information system, collating all reports that
      included the word "nasogastric" from 1 January 2010 until 15 May 2011. For each
      report the description of tube position was put in one of six categories from
      "fully compliant with NPSA [National Patient Safety Agency] requirements" to
      "image missing". In a second, smaller dataset (cases in which some anatomy was
      described), we investigated the position of the tube tip as classified using
      descriptions from radiology reports. None of the reports contained all of the
      information required to comply with NSPA's (2011) guidelines, but most
      nasogastric tubes (70%) were in the stomach. Twenty-one per cent were reported as
      being in the oesophagus; advice varied from advancing it further (if
      uncomplicated) to removing it (if coiled or looped). Four per cent of tubes were
      seen in the airways (lung or bronchus) with advice for immediate removal.

PMID- 23167061
TI  - New guidance on the insertion of balloon gastrostomy.

PMID- 23167062
TI  - PEG feeding tube placement and aftercare.
AB  - Some adults and children are unable to swallow or eat and drink enough. Insertion
      of a percutaneous endoscopic gastrostomy (PEG) tube may enable long-term feeding,
      fluid and/or medication administration. The procedure involves gastroscopy under
      sedation to identify tube placement site, place the tube and check it has been
      placed correctly. Serious complications include peritonitis and perforation of
      the colon. Frequent observations immediately after placement are essential. With
      good nursing care, complications can be avoided or dealt with promptly.

PMID- 23167063
TI  - Dehydration in stroke patients admitted to hospital.

PMID- 23167064
TI  - Using Rapid Spread improve hospital nutrition.
AB  - This article describes how we changed nutritional care throughout our trust. To
      carry out our "nutrition mission", we used change methodology known as Rapid
      Spread. This programme of change gave our health professionals a step-by-step
      approach to bringing in and sustaining excellent evidence-based nutritional care
      across our trust very quickly. Since the initiative, there has been a massive
      improvement in the nutritional care of patients.

PMID- 23167065
TI  - Looks good enough to eat.

PMID- 23167066
TI  - [Appeal to strength. Why there is a need for appreciation for the positive side
      of informal care].

PMID- 23167067
TI  - [Positive experience through informal care: construction of a scale].
AB  - An 8-item scale has been developed to measure positive experiences by informal
      caregivers, the Positive Experiences Scale (PES). The PES is a unidimensional
      hierarchical Mokkenscale which varies from intrinsic satisfaction and relational
      enhancement to improvement of competence and social enhancement. The scale has a
      satisfactory Loevinger's H-value (0.37) and reliability (0.74). Furthermore,
      satisfying H-values are found for large groups of informal caregivers, such as
      carers for the elderly, the chronically ill, partners, parents and people who
      live in a care facility. For informal caregivers of people with dementia or
      mental impairments, two items do not uphold ('I received appreciation for the
      care I've been giving' and 'the help brought me and my family and friends closer
      together'. For these groups a 6-item scale is advised. Solely for informal
      caregivers of people with psychological impairments, the scale as a whole does
      not uphold. Further research will have to determine how these caregivers derive
      positive experiences from caregiving. The PES is recommended because of its
      psychometric qualities and its usefulness in different populations of informal
      caregivers.

PMID- 23167068
TI  - [Dementia in documentary film: Mum by Adelheid Roosen].
AB  - This article draws attention to the fact that documentaries do not simply
      reproduce the reality that film and audience share but always present a
      particular view of this reality. This implies that organizations in Alzheimer
      care, education, and research that often recommend documentaries to inform people
      about dementia should take into account that these films might reinforce negative
      stereotypes inducing fear of dementia. An in-depth analysis of the Dutch short
      documentary Mum, directed by Adelheid Roosen, illustrates that the body of ideas
      of the personhood movement in dementia research can be translated into an
      artistic form. By highlighting instead of veiling its means of production, the
      documentary stimulates viewers to imagine people with dementia as other than lost
      selves. The original version of this article in The Gerontologist was made
      available April 26, 2012.

PMID- 23167069
TI  - [18 FDG PET imaging of the brain in the analysis of a dementia syndrome].
AB  - According to current dementia guidelines from 2005 (CBO) functional brain imaging
      by PET-scan of the brain has no place in the analysis of a dementia syndrome.
      Differential diagnosis between Alzheimer disease and other causes of dementia
      remains important because there are differences in natural course and treatment.
      Here we present three patients aged 62, 71 and 68 years with dementia syndrome
      who were assessed at an outpatient memory clinic. After geriatric assessment and
      subsequent brain MRI the etiology of the dementia remained unclear. In all three
      patients the etiology became clear after using a 18 FDG PET-scan of the brain. We
      conclude that 18 FDG PET imaging of the brain has added value in the analysis of
      dementia syndrome with an unclear etiology after initial analysis.

PMID- 23167070
TI  - [Clinimetrics: is there room for a smart scale which measures balance?].

PMID- 23167071
TI  - [Education in gynecologic surgery].

PMID- 23167072
TI  - [Endometriosis: an essential differential diagnosis of chronic pelvic pain].
AB  - In the context of chronic pelvic pain, endometriosis plays a significant role due
      to its frequency and its effects on the quality of women's lives. It affects 3
      10% of women of reproductive age. The clinical signs are part from chronic pelvic
      pain, dysmenorrhea, dyspareunia, urinary and digestive symptoms as well as
      infertility. The clinical signs and symptoms may vary and the clinical
      examination may be difficult to interpret for a physician who is not familiar
      with the condition. This explains the fact that it takes more time to make the
      diagnosis of endometriosis. Delay of diagnosis, multiple consultations and
      complex surgical procedures implicate physical and psychological suffering for
      the patient with serious complications. For all these reasons, the differential
      diagnosis of chronic pelvic pain in women should include endometriosis.

PMID- 23167073
TI  - [Indications and techniques of reconstruction after mastectomy].
AB  - Reconstructive surgery takes an important place in breast cancer treatment.
      Immediate breast reconstruction is performed during the same operation as
      mastectomy. It is contraindicated following radiotherapy. Reconstruction
      performed after mastectomy is called differed breast reconstruction. It is
      completed 6 months after chemotherapy and 1 year after radiotherapy. Prosthetic
      breast reconstruction is indicated when tissues are of good qualities and breast
      are small. Autologous reconstruction is performed in case of radiotherapy or
      large breast. After breast reconstruction, imperfections can be corrected with
      autologous fat injection.

PMID- 23167074
TI  - [Contraception and bone health in adolescence].
AB  - Adolescents' access to contraception has improved and indication for their use
      have been extended beyond pregnancy prevention. For adolescents, this implies the
      use of hormonal contraception before the accrual of peak bone mass. Sexual
      hormones, notably estrogens, play a major role in skeletal development, growth
      and acquisition of maximal bone mass density (BMD). This article will review
      different contraceptive methods and their impact on BMD, with particular
      attention to low-dose pills and medroxyprogesterone acetate, both of which seem
      to alter peak bone mass acquisition. Nevertheless, benefits from appropriate
      contraception should be weighed against safety concerns, and recommended on an
      individual basis.

PMID- 23167075
TI  - [Fast track in gynecological surgery].
AB  - The concept of fast track surgery (FT) is a multimodal strategy aiming to
      decrease postoperative pains and chirurgical stress-induced organ dysfunction.
      The key elements of this program are: information and preoperative education,
      perioperative hydric balance, optimized analgesia, early oral nutrition and early
      mobilization of the patients. A multidisciplinary teamwork is essential. FT
      program is applicable in open surgery and in laparoscopy and has proven its
      effectiveness in colorectal surgery. Using this strategy in gynecological
      surgery, which resembles it in many points, will prove its effectiveness and
      facilitate its wider implementation.

PMID- 23167076
TI  - [Cervical cancer prevention in Switzerland: the challenges of the vaccine era].
AB  - In Switzerland, cervical cancer screening has been introduced in the 60s and has
      allowed a significant reduction in the incidence and mortality of this disease.
      More recently, the HPV vaccine was introduced with public target of girls aged 11
      to 14 years. Gradually, this vaccinated population will reach the age of
      screening. Vaccinated population will present less HPV infection and less
      cytological abnormalities and consequence will conduct to a lower performance of
      cytology. In this context, the HPV test with its objectivity will become the most
      suitable means for cervical cancer screening. The aim of this paper was to
      conduct a synthesis of current knowledge about primary and secondary prevention
      of cervical cancer and define the best options for the future.

PMID- 23167077
TI  - [Performance of ultrasound estimation of fetal weight in fetuses weighing < or =
      2000 g and more than 4000 g].
AB  - Decreasing perinatal morbidity and mortality is one of the main goals of
      obstetrics. Prognosis of preterm births depends on gestational age and
      birthweight. Multidisciplinary management is discussed with the parents according
      to these two parameters. In other circumstances, a suspected macrosomy will
      influence the management of the last weeks of pregnancy. Induction of labor or
      Cesarean delivery will be considered to avoid shoulder dystocia, brachial plexus
      injury or perinatal asphyxia. Birthweight needs to be estimated with accuracy,
      and this article describes the efficiency of various ultrasound weight estimation
      formulae for small and large fetuses.

PMID- 23167078
TI  - [Vertigo].

PMID- 23167079
TI  - [Two rapid diagnostic tests for multiple antibacterial resistance].

PMID- 23167080
TI  - [Numbers and letters].

PMID- 23167081
TI  - [Badgers, oocytes and alcohol: a weekend at London].

PMID- 23167082
TI  - [Same-sex marriage].

PMID- 23167083
TI  - [Should we be wary of UpToDate?].

PMID- 23167084
TI  - The social determinants of health.

PMID- 23167085
TI  - The making of a neurosurgeon. Harvey Cushing, Halstedian technique, and the birth
      of a specialty.

PMID- 23167086
TI  - Is there a doctor Hertzler in the house?

PMID- 23167087
TI  - An afternoon with physician-poet John Stone.

PMID- 23167088
TI  - Thinking doctor. The road to healing.

PMID- 23167089
TI  - Daylon.

PMID- 23167090
TI  - Chicken fried.

PMID- 23167091
TI  - The Pharos on mentoring and coaching.

PMID- 23167092
TI  - [Effectiveness analysis of arthroscopically assisted treatment of rotator cuff
      injury].
AB  - OBJECTIVE: To explore the method and effectiveness of arthroscopically assisted
      treatment of rotator cuff injury. METHODS: Between November 2009 and March 2011,
      27 patients with rotator cuff injury were treated. There were 17 males and 10
      females with a mean age of 43.6 years (range, 29-66 years). The disease duration
      was 1 to 36 months (mean, 27 months). The location was the left shoulder in 11
      cases and the right shoulder in 16 cases. Of them, 12 cases had a history of
      trauma and 15 cases had no obvious predisposing causes. All patients had
      limitation of shoulder flexion and abduction. Anteroposterior and lateral X-ray
      films of the shoulder and the out-let X-ray films of the supraspinous muscle were
      taken. According to the acromion classification of Bigliani, there were 5 cases
      of type I, 13 cases of type II, and 9 cases of type III. MRI images showed all
      patients had rupture of the rotator cuff. The examination of shoulder arthroscope
      showed complete rupture of the supraspinatus muscle in 27 cases and acromion
      impingement in 23 cases. The patients without impingement underwent tear
      debridement, and the patients with impingement underwent acromioplasty and
      resection of subacromial bursa after tear debridement. The 3-4 cm incision was
      made with arthroscopically assisted positioning, and the metal suture anchor was
      placed on the greater tubercle of humerus to repair rotator cuff. RESULTS: All
      incisions healed primarily. All patients were followed up 13-27 months (mean, 19
      months). No infection, loosening of internal fixation, and rotator cuff re-tear
      occurred. Pain was relieved and the results was satisfactory after operation. The
      shoulder range of motion (ROM) at last follow-up was significantly improved when
      compared with preoperative ROM (P < 0.05). The visual analogue scale (VAS) score
      was significantly improved from 8.0 +/- 1.8 at preoperation to 1.6 +/- 0.7 at 2
      weeks after operation and 0.8 +/- 0.7 at last follow-up (P < 0.05); the
      University of California Los Angeles (UCLA) score of shoulder was significantly
      increased from 18.8 +/- 6.6 at preoperation to 32.2 +/- 3.3 at 3 months after
      operation and 33.6 +/- 2.1 at last follow-up (P < 0.05). CONCLUSION: The
      effectiveness of arthroscopically assisted treatment of rotator cuff injury is
      satisfactory. However, long-term effectiveness needs further follow-up
      observation.

PMID- 23167093
TI  - [Effectiveness of double-needle suture for mixed meniscus tear repair under
      arthroscope].
AB  - OBJECTIVE: To investigate the effectiveness of double-needle suture for mixed
      meniscus tear repair under arthroscope. METHODS: Between April 2006 and January
      2011, 22 patients with mixed meniscus tear were treated with double-needle suture
      under arthroscope. There were 14 males and 8 females, aged 18-41 years (mean,
      31.3 years). All injuries were caused by sports. The time between injury and
      admission ranged from 2 days to 4 years (median, 11 months). International Knee
      Documentation Committee (IKDC) score was 42.5 +/- 15.2, Lysholm score was 45.5 +/
      13.5, and Tegner score was 2.9 +/- 1.6. Seventeen cases complicated with
      anterior cruciate ligament injury. RESULTS: Healing of incision by first
      intention was achieved in all patients. No injury of nerve and blood occurred.
      The patients were followed up 12-48 months with an average of 27.6 months.
      According to Barrett et al. standard, 19 cases (86%) got clinical healing. The
      IKDC, Lysholm, and Tegner scores were improved to 77.1 +/- 8.9, 79.8 +/- 9.9, and
      6.8 +/- 1.6 respectively at last follow-up, showing significant differences when
      compared with preoperative scores (P < 0.05). Co CONCLUSION: Arthroscopic
      meniscus repair using double-needle suture can provide good effectiveness because
      it has high firmness.

PMID- 23167094
TI  - [Acetabular reconstruction surgery in treatment of pathological dislocation of
      hip joint in children].
AB  - OBJECTIVE: To investigate the effectiveness of the acetabular reconstruction
      surgery in children pathological dislocation of the hip joint. METHODS: Between
      January 2006 and January 2011, 59 patients (59 hips) with pathological
      dislocation were treated by open reduction combined with acetabular
      reconstruction surgery. There were 22 boys and 37 girls, aged from 1 to 15 years
      (mean, 4.9 years). There were 9 cases of hip subluxation and 50 cases of hip
      joint dislocation, which were caused by suppurative arthritis of the hip (33
      cases) and tuberculosis of the hip (26 cases). The diseases duration ranged from
      1 month to 10 years. At preoperation Harris hip score was 43-78 (mean, 61); 14
      cases had normal acetabular index (AI), 32 cases had slightly increased AI, and
      13 cases had significantly increased AI. The concomitant diseases included
      acetabular destruction in 28 cases; avascular necrosis of the femoral head in 25
      cases, femoral head partial defect in 12 cases, femoral head complete defect in 6
      cases, and femoral head and neck defects in 3 cases; 25 cases had increased
      anteversion angle; and 9 cases had varus deformity. RESULTS: Immediately
      postoperative X-ray films showed center reduction in all the hips. Healing of
      incision by first intention was achieved in 55 cases, and delayed healing in 4
      cases. Fifty-three children were followed up 2 to 5 years (mean, 3 years). No re
      dislocation of the hip occurred during follow-up. Thirty-eight cases had normal
      AI, 15 cases had slightly increased AI. The anteversion angle was 15-25 degrees
      (mean, 20 degrees); the neck shaft angle was 110-140 degrees (mean, 125 degrees);
      and the anatomical relation between the head and neck returned to normal. After 2
      years, 18 cases had normal function of the hip joint; 30 cases had mild
      limitation of flexion and rotation; and 5 cases had fibrous ankylosis. The Harris
      hip score was 62-95 (mean, 87). CONCLUSION: Pathological dislocation caused by
      neonatal acute suppurative arthritis of the hip and the hip joint tuberculosis is
      often associated with severe bone destruction and deformity of the acetabular and
      femoral head and neck. Treatment should strictly follow the principle of
      individual. Proper acetabular reconstruction should be selected according to
      pathological changes of the hip; if combined with the femoral head and neck
      reconstruction processing, the satisfactory results can be obtained.

PMID- 23167095
TI  - [Long-term follow-up of early-middle stage avascular necrosis of femoral head
      with core decompression and bone grafting].
AB  - OBJECTIVE: To evaluate the long-term effectiveness of treating early-middle stage
      avascular necrosis of the femoral head (ANFH) with core decompression and bone
      grafting. METHODS: Between January 2000 and December 2006, 87 ANFH patients (114
      hips) were treated with core decompression and bone grafting, including 54 cases
      (62.1%) of alcohol-induced ANFH, 26 cases (29.9%) of steroid-induced ANFH, and 7
      cases (8.0%) of idiopathic ANFH. There were 74 males (97 hips) and 13 females (17
      hips), aged 20-56 years (mean, 38 years). The disease duration was 3-46 months
      (mean, 18 months). According to Ficat staging, 16 hips were at stage I, 68 hips
      at stage II, and 30 hips at stage III. The Harris score and Ficat stage were
      compared between pre- and post-operation to assess the outcomes clinically and
      radiologically. The hip survival was analyzed by the Kaplan-Meier method.
      RESULTS: Eighty-seven patients were followed up 5 years to 11 years and 10 months
      (mean, 8 years and 9 months). The Harris hip score was significantly increased
      from 73.13 +/- 7.17 at preoperation to 81.59 +/- 13.23 at postoperation (t = 
      9.318, P = 0.000). The clinical success rate was 69.3% (79/114) and the
      radiological success rate was 54.4% (62/114). Kaplan-Meier survival analysis
      showed that the overall survival rate was 84.2% (96/114); the survival rates of
      Ficat stage I [100% (16/16)] and stage II [91.2% (62/68)] were higher than that
      of stage III [60.0%(18/30)] (P < 0.01); there was no significant difference
      between Ficat stage I and II (chi2 = 1.520, P = 0.218). CONCLUSION: Core
      decompression with bone grafting is a safe and effective procedure for the
      treatment of Ficat stages I-II (early stage) ANFH, and the long-term
      effectiveness is satisfactory. But the long-term effectiveness is unsatisfactory
      for the patients at the Ficat stage III (middle stage).

PMID- 23167096
TI  - [Two-stage revision of infected total knee arthroplasty using antibiotic
      impregnated articulating cement spacer].
AB  - OBJECTIVE: To investigate the effectiveness of two-stage revision of infected
      total knee arthroplasty (TKA) using an antibiotic-impregnated articulating cement
      spacer. METHODS: The clinical data were analyzed from 23 patients (23 knees)
      undergoing two-stage revision for late infection after primary TKA between
      January 2007 and December 2009. There were 15 males and 8 females, aged from 43
      to 75 years (mean, 65.2 years). Infection occurred at 13-52 months (mean, 17.3
      months) after TKA. The time interval between infection and admission ranged from
      15 days to 7 months (mean, 2.1 months). One-stage operation included surgical
      debridement and removal of all knee prosthesis and cement, then an antibiotic
      impregnated articulating cement spacer was implanted. The re-implantation of
      prosthesis was performed after 8-10 weeks when infections were controlled. The
      American Hospital for Special Surgery (HSS) score and Knee Society Score (KSS)
      were used to compare the function of the knee between pre- and post-revision. The
      rate of infection control and complication were analyzed. RESULTS: All incisions
      healed primarily. Re-infection occurred in 2 cases after two-stage revision, and
      infection was controlled in the other 21 cases, with an infection control rate of
      91.3%. The patients were followed up 2-5 years (mean, 3.6 years). The HSS score
      was increased from 60.6 +/- 9.8 at pre-revision to 82.3 +/- 7.4 at last follow
      up, the KSS score was increased from 110.7 +/- 9.6 at pre-revision to 134.0 +/-
      10.5 at last follow-up, all showing significant differences (P < 0.01).
      Radiographs showed that prosthesis had good position with no loosening, fracture,
      or periprosthetic radiolucent. CONCLUSION: Two-stage revision using an antibiotic
      impregnated articulating cement spacer is an effective method to control infected
      TKA and to restore the function of affected knee.

PMID- 23167097
TI  - [Impact of differences of posterior condyle cartilage wear on rotational
      positioning of femoral prosthesis in total knee arthroplasty for osteoarthritis
      patients].
AB  - OBJECTIVE: To investigate the impact of difference between the medial and lateral
      posterior condyle cartilage thickness on osteotomy in total knee arthroplasty
      (TKA) by measuring the thickness of the medial and lateral femur posterior
      condylar cartilage and the posterior condylar angle (PCA) in osteoarthritis (OA)
      patients. METHODS: Between May and December 2011, 53 OA patients (60 knees)
      scheduled for TKA met the inclusion criteria (OA group). There were 12 males (14
      knees) and 41 females (46 knees), aged 57-82 years (mean, 71.9 years). The
      tibiofemoral angle was (183.2 +/- 2.6) degrees. Fifteen healthy volunteers (30
      knees) were taken as controls (control group); there were 6 males and 9 females,
      aged 59-68 years (mean, 66.3 years). MRI scan data were imported into Mimics
      10.01 medical image control system to measure the thickness of femur posterior
      condylar cartilage and the PCA with and without femur posterior condylar
      cartilage. RESULTS: In the control group, the thickness of the medial and lateral
      femur posterior condylar cartilage was (1.85 +/- 0.33) mm and (1.92 +/- 0.27) mm
      respectively, the PCA with and without femur posterior condylar cartilage was
      (5.0 +/- 0.9) degrees and (5.1 +/- 0.8) degrees respectively, all showing no
      significant differences (P > 0.05). In OA group, the thickness of the medial and
      lateral femur posterior condylar medial cartilage was (0.45 +/- 0.40) mm and
      (1.78 +/- 0.51) mm respectively, the PCA with and without femur posterior
      condylar cartilage was (3.3 +/- 1.7) degrees and (4.8 +/- 1.8) degrees
      respectively, all showing significant differences (P < 0.05). In OA group, the
      difference between lateral and medial cartilage thickness was (1.33 +/- 0.45) mm,
      and the difference between PCA with and without femur posterior condylar
      cartilage was (1.5 +/- 1.3) degrees. There was a positive correlation between the
      difference of cartilage thickness and the difference of PCA (r = 0.75, P = 0.01).
      CONCLUSION: There is significant difference between medial and lateral femur
      posterior condylar cartilage wear, which leads to difference of PCA. The
      difference will impact knee function and longevity of the prosthesis, so the
      difference should be considered during osteotomy.

PMID- 23167098
TI  - [Treatment of fresh closed fracture-dislocation of midtarsal joint].
AB  - OBJECTIVE: To investigate the treatment method and effectiveness of fresh closed
      fracture-dislocation of the midtarsal joint. METHODS: Between April 2004 and
      April 2011, 73 patients (75 feet) with fresh closed fracture-dislocation of the
      midtarsal joint were treated with closed reduction combined with open reduction
      and internal fixation. There were 56 males (58 feet) and 17 females (17 feet),
      aged from 19 to 62 years (mean, 35.8 years). Injuries were caused by falling from
      height in 35 cases, by sprain in 4 cases, by machine twist in 5 cases, by heavy
      pound in 9 cases, and by traffic accident in 20 cases. The time from injury to
      admission ranged from 1 hour and 30 minutes to 48 hours (mean, 4.5 hours).
      According to Main's classification standard, 6 feet were rated as vertical
      compression injury, 33 feet as medial displacement injury, 17 feet as lateral
      displacement injury, 9 feet as flexion injury, and 10 feet as crush injury.
      Concomitant injuries included midfoot fracture-dislocation (34 feet), scaphoid
      fracture (6 feet), cuboid bone fracture (18 feet), calcaneal fracture (8 feet),
      talus fracture (7 feet), tibiotalar joint dislocation (2 feet), subtalar joint
      dislocation (2 feet), medial malleolus fracture (1 foot), and acute compartment
      syndrome (3 feet). RESULTS: Healing of incision by first intention was achieved
      in 65 cases (67 feet), by second intention in 8 cases (8 feet). Sixty-two cases
      (62 feet) were followed up from 11 months to 7 years and 11 months (mean, 3 years
      and 6 months). After operation, feet pain occurred in 26 cases, and stiffness or
      discomfort of the affected foot in 36 feet when walking. The X-ray examination
      showed good reduction of fracture-dislocation of the midtarsal joint and
      concomitant injuries with no re-dislocation or bone nonunion in 59 feet; 3 feet
      had flatfoot secondary to navicular necrosis, and underwent arthrodesis. The
      American Orthopaedic Foot and Ankle Society (AOFAS) score was 77-90 (mean, 88.6)
      at last follow-up. CONCLUSION: According to the preoperative evaluation of the
      damage, using the manual reduction combined with internal fixation (mini-plate or
      hollow screw with Kirschner wire) methods can obtain good effectiveness in the
      treatment of fracture-dislocation of the midtarsal joint.

PMID- 23167099
TI  - [Three-dimensional visualization of intercondylar notch based on MRI two
      dimensional images].
AB  - OBJECTIVE: To study the feasibility of virtual intercondylar notchplasty by
      applying MRI two-dimensional (2D) images to reconstruct three-dimensional (3D)
      images and measure the size of intercondylar notch. METHODS: Thirty healthy
      volunteers who had no knee joint disease and surgery history were selected. There
      were 15 females and 15 males with an age range of 20-30 years, weight range of 45
      74 kg, and height range of 150-185 cm. They were divided into male group and
      female group, and the knees of each group were divided into 2 subgroups (the left
      group and right group). MRI scan of the left and right knees was performed, and
      the 2D images of MRI were imported into Mimics 10.01 medical image control system
      for 3D reconstruction. The related anatomical data as follows were measured from
      the 3D digital model and analyzed by statistical software: notch width (NW),
      condylar width (CW), and notch width index (NWI). Then the 3D knee images of
      patients with anterior cruciate ligament (ACL) injury were collected between
      January and March 2010, and 4 patients with narrow intercondylar notch (NWI < or
      = 0.2) were selected for reconstructing the 3D model of the knee and simulating
      the intercondylar notch plasty. Then, the volume of osteotomy in 3D model was
      calculated and applied in the ACL reconstruction surgery, and whether the graft
      had impingement with intercondylar notch or not was evaluated. RESULTS: There
      were significant differences in NW and CW between male group and female group (P
      < 0.05), but no significant difference was found in the NWI (P > 0.05). And there
      was no significant difference in NW, CW, and NWI between the left and right knees
      both in male group and female group (P > 0.05). After ACL reconstruction and
      intercondylar notchplasty, the shape of intercondylar notch became normal (NWI >
      0.22), no impingement occurred between the graft and intercondylar notch under
      arthroscopy within 3-month follow-up. CONCLUSION: The shape of intercondylar
      notch of 3D model based on MRI 2D images is similar to the real intercondylar
      notch. NWI is one of important indexes which can reflect the narrow level of
      intercondylar notch. The virtual intercondylar notchplasty may provide
      preoperative plan and guidence for ACL reconstruction operation to avoid the
      impingement between graft and intercondylar notch after surgery.

PMID- 23167100
TI  - [Research progress of protective effects of alendronate on articular cartilage in
      osteoarthritis].
AB  - OBJECTIVE: To summarize the recent development on chondroprotective effect of
      alendronate (ALN) on articular cartilage in osteoarthritis (OA). METHODS: The
      related literature was reviewed and the main achievements in vitro/vivo studies
      in the fields were summarized. RESULTS: ALN can improve the metabolic
      microenvironment of the articular cartilage in OA, inhibit subchondral bone
      remodeling, so it has potential protective effect on articular cartilage.
      CONCLUSION: ALN is expected to become a disease-modifying OA drug in future, but
      OA treatment still lack a uniform basic and clinical evaluation criteria, so it
      has guiding significance in development and application of ALN to develope a
      uniform standard and obtain the clinical data.

PMID- 23167101
TI  - [Comparison of effectiveness between laminoplasty and laminectomy decompression
      and fusion with internal fixation for cervical spondylotic myelopathy].
AB  - OBJECTIVE: To compare the clinical and radiographic outcomes between laminoplasty
      and laminectomy compression and fusion with internal fixation to treat cervical
      spondylotic myelopathy. METHODS: Between September 2006 and September 2009, 143
      cases of multilevel cervical myelopathy (the affected segments were more than 3)
      were treated by laminoplasty in 87 cases (group A) and by laminectomy
      decompression and fusion with lateral mass screw fixation in 56 cases (group B).
      There was no significant difference in gender, age, disease duration,
      pathological type, and affected segments between 2 groups (P > 0.05). The
      operation time, intraoperative blood loss, improvement of neurological function
      [Japanese Orthopaedic Association (JOA) 17 score], and the incidences of
      complications were observed; the cervical curvature index (CCI), range of motion
      (ROM), and symptoms of neck and shoulder pain [visual analogue scale (VAS) and
      neck disability index (NDI) scores] were recorded and compared. RESULTS: There
      was no significant difference in operation time and intraoperative blood loss
      between 2 groups (P > 0.05). All patients were followed up 18-30 months (mean, 24
      months). C5 nerve root palsy occurred in 4 cases (4.60%) of group A and in 5
      cases (8.93%) of group B, showing no significant difference (chi2 = 0.475, P =
      0.482). No complication of deep infection, pseudarthrosis, or screw loosening
      occurred. No closure of opened laminae was observed in group A; and no screw
      extrusion, breakage, or nerve injury was observed in group B. At last follow-up,
      neck axial symptoms appeared in 35 cases (40.23%) of group A and in 11 cases
      (19.64%) of group B, showing significant difference (chi2 = 6.612, P = 0.009). No
      significant difference was found in JOA score, CCI, ROM, or VAS scores between 2
      groups at preoperation (P > 0.05); the JOA score, ROM, and VAS scores of groups A
      and B and CCI of group A at last follow-up were significantly improved when
      compared with preoperative ones (P < 0.05). No significant difference was found
      in the JOA score, improvement rate, and VAS score between 2 groups (P > 0.05);
      however, significant differences were found in ROM and CCI between 2 groups (P <
      0.05). There were significant differences (P < 0.05) in pain intensity, lifting,
      work, reaction, driving, and total score between 2 groups at last follow-up.
      CONCLUSION: Laminectomy decompression and fusion with internal fixation can
      effectively relieve pain, but it will greatly reduce the ROM; laminoplasty has
      less complications and satisfactory outcome. The two methods have similar
      effectiveness in the improvement of neurological function.

PMID- 23167102
TI  - [Restoration of thoracic kyphosis with multilevel Ponte osteotomies in thoracic
      idiopathic scoliosis surgery].
AB  - OBJECTIVE: To investigate the effectiveness of multilevel Ponte osteotomies on
      maintenance and restoration of thoracic kyphosis in idiopathic scoliosis (IS)
      surgery. METHODS: Between March 2008 and February 2010, 42 patients with thoracic
      IS (Lenke type 1 curves) were corrected with posterior pedicle screw system.
      Multilevel Ponte osteostomies for posterior release was performed in 17 cases
      (group A), and the 3 segments near the apical vertebrae were selected as the
      osteotomy site; simple posterior soft tissue release was given in 25 cases (group
      B). There was no significant difference in sex, age, disease duration, lesion
      segments, coronary Cobb angle, thoracic kyphosis, Risser index, and bending
      flexibility between 2 groups (P > 0.05). The anteroposterior and lateral standing
      radiographs of the spine were taken to compare the effectiveness between 2
      groups. RESULTS: Operation was successfully completed in all patients. The
      operation time and blood loss in group A were significantly greater than those in
      group B (P < 0.05). Spine dural injury and leakage of cerebrospinal fluid
      occurred in 1 case of group A, which was cured after compression on local area of
      the wound; the other patients had no intraoperative complications. The patients
      were followed up 2-4 years (mean, 2.8 years); no nerve injury, infection, or
      internal fixation failure occurred. No obvious correction loss was observed and
      the appearance and trunk balance were significantly improved. The coronal Cobb
      angles at 1 week and 2 years after operation were significantly improved when
      compared with preoperative ones in 2 groups (P < 0.05). There was no significant
      difference in the coronal Cobb angle and correction rate between 2 groups at 1
      week and 2 years after operation (P > 0.05). Group A was significantly better
      than group B in the thoracic kyphotic angle and angle changes at 1 week and 2
      years after operation (P < 0.05). CONCLUSION: The posterior approach surgery with
      multilevel Ponte osteotomies can restore the thoracic kyphosis in IS, but it has
      no effect on coronal correction in Lenke type 1 curves.

PMID- 23167103
TI  - [Preliminary application of absorbable fixation system on cranial bone flap
      reposition and fixation after craniotomy].
AB  - OBJECTIVE: To investigate the effectiveness and adverse effect of the absorbable
      fixation system on cranial bone flap reposition and fixation after craniotomy.
      METHODS: Between July 2010 and December 2011, 67 cases underwent cranial bone
      flap reposition and fixation with absorbable fixation system after craniotomy and
      resection of intracranial lesions. There were 38 males and 29 females with a
      median age of 32 years (range, 5 months to 73 years). The disease duration ranged
      from 3 months to 6 years (median, 25 months). Forty-one lesions were located at
      supratentorial and 26 at subtentorial, including at the frontotemporal site in 13
      cases, at the frontoparietal site in 12 cases, at the temporal oprietal site in 8
      cases, at the temporooccipital site in 5 cases, at the occipitoparietal site in 4
      cases, and at the posterior cranial fossa in 25 cases. The diagnosis results were
      glioma in 15 cases, cerebral vascular diseases (aneurysm, arteriovenous
      malformation, and cavemous angioma) in 8 cases, meningioma in 7 cases, arachnoid
      cyst in 7 cases, acoustic neurinoma in 5 cases, cholesteatoma in 3 cases, primary
      trigeminal neuralgia in 5 cases, cerebral abscess in 3 cases, hypophysoma in 2
      cases, craniopharyngioma in 2 cases, metastatic tumor in 2 cases, radiation
      encephalopathy in 2 cases, medulloblastoma in 1 case, ependymocytoma in 1 case,
      germinoma in 1 case, atypical teratoma/rhabdoid tumor in 1 case, facial spasm in
      1 case, and subdural hematoma in 1 case. Intracranial lesion size ranged from 3
      cm x 2 cm to 7 cm x 5 cm. The changes of local incision and general condition
      were observed. RESULTS: Subcutaneous effusion occurred in 2 supratentorial
      lesions and 3 subtentorial lesions, which was cured at 2 weeks after puncture and
      aspiration. All incisions healed primarily and no redness or swelling occurred.
      CT scans showed good reposition of the cranial bone flap and smooth inner and
      outer surfaces of the skull at 2 weeks after operation. All 67 patients were
      followed up 3-20 months (mean, 10.3 months). During follow-up, the skull had
      satisfactory appearance without discomfort, local depression, or effusion.
      Moreover, regular CT and MRI scans showed no subside, or displacement of the
      cranial bone flap or artifacts. CONCLUSION: Absorbable fixation system for
      reposition and fixation of the cranial bone flap not only is simple, safe, and
      reliable, but also can eliminate the postoperative CT or MRI artifact caused by
      metals fixation system.

PMID- 23167104
TI  - [One-stage repair of pharyngeal defect using tongue flaps after resection of
      advanced stage hypopharyngeal neoplasm and laryngeal neoplasm].
AB  - OBJECTIVE: To study the effectiveness of one-stage repairing pharyngeal defect
      with the tongue flaps after resection of advanced stage hypopharyngeal neoplasm
      and laryngeal neoplasm. METHODS: Between June 2006 and March 2011, 20 patients
      with hypopharyngeal neoplasm (8 cases) and laryngeal neoplasm (12 cases) with
      advanced stage were treated. There were 19 males and 1 female, aged 47-78 years
      (mean, 62.8 years). All neoplasms were squamous cell carcinomas. The disease
      duration was 1-8.5 months (mean, 3.9 months). According to the standards of
      International Union Against Cancer (UICC, 1987), 12 cases were in stage III and 8
      cases were in stage IV. The size of pharyngeal defect was 5 cm x 2 cm to 4 cm x 4
      cm after resection of tumor. Defects were repaired by the whole base of the
      tongue flaps in 16 cases and by the horizontal base of the tongue flaps in 4
      cases. The size of the flaps ranged from 5 cm x 2 cm to 4 cm x 4 cm.
      Postoperative radiotherapy and chemotherapy were regularly performed. RESULTS:
      The 20 tongue flaps were alive. Healing of incision by first intention was
      achieved in 18 cases and delayed healing in 2 cases because of subcutaneous
      fluid. The patients were followed up 12-63 months (mean, 36.7 months). The
      patients had normal feeding ability and tongue function. Of 20 cases, 12 died and
      1 of local recurrence was alive with tumor. The 3-year survival rate was 69.2%
      (9/13). CONCLUSION: One-stage repair of pharyngeal defect with the tongue flaps
      after resection of hypopharyngeal neoplasm and laryngeal neoplasm can obtain good
      effectiveness because the tongue flap is easy-to-obtain and easy-to-survive, and
      has abundant blood supply.

PMID- 23167105
TI  - [Anterolateral thigh fasciocutaneous flap for repair of open Achilles tendon
      defect].
AB  - OBJECTIVE: To explore the effectiveness of anterolateral thigh fasciocutaneous
      flap for repair of skin and soft tissue defect and simultaneous Achilles tendon
      reconstruction with modified methods of ilio-tibial bundle suture. METHODS:
      Between October 2009 and June 2011, 10 cases of Achilles tendon and soft tissue
      defects were treated. There were 7 males and 3 females, aged from 5 to 60 years
      (median, 40 years). Injury was caused by spoke in 5 cases, by heavy pound in 3
      cases, and by traffic accident in 2 cases. The time between injury and admission
      was 2-24 hours (mean, 8 hours). The size of wound ranged from 11 cm x 7 cm to 18
      cm x 10 cm; the length of Achilles tendon defect was 4-10 cm (mean, 7 cm). Three
      cases complicated by calcaneal tuberosity defect. After admission, emergency
      debridement and vacuum sealing drainage were performed for 5-7 days,
      anterolateral thigh fasciocutaneous flap transplantation of 11 cm x 7 cm to 20 cm
      x 12 cm was used to repair skin and soft tissue defects, and improved method of
      ilio-tibial bundle suture was used to reconstruct Achilles tendon. The flap donor
      site was closed directly or repaired with skin grafting to repair. RESULTS: All
      flaps and the graft skin at donor site survived, healing of wounds by first
      intention was obtained. All patients were followed up 6-18 months (mean, 10
      months). The flap was soft and flexible; the flap had slight encumbrance in 3
      cases, and the others had good appearance. At last follow-up, two-point
      discrimination was 2-4 cm (mean, 3 cm). The patients were able to walk normally.
      The range of motion (ROM) of affected side was (24.40 +/- 2.17) degrees extension
      and (44.00 +/- 1.94) degrees flexion, showing no significant difference when
      compared with ROM of normal side [(25.90 +/- 2.33) degrees and (45.60 +/-
      1.84)degrees] (t = 1.591, P = 0.129; t = 1.735, P = 0.100). According to Arner
      Lindhoim assessment method for ankle joint function, all the patients obtained
      excellent results. CONCLUSION: A combination of anterolateral thigh
      fasciocutaneous flap for repair of skin and soft tissue defects and simultaneous
      Achilles tendon reconstruction with modified methods of ilio-tibial bundle suture
      is beneficial to function recovery of the ankle joint because early function
      exercises can be done.

PMID- 23167106
TI  - [Biomechanical research of less invasive stabilization system and dynamic
      condylar screw in fixing subtrochanteric fractures of femur].
AB  - OBJECTIVE: To compare the biomechanical characteristics of the less invasive
      stabilization system (LISS) and the dynamic condylar screw (DCS) in the fixation
      of subtrochanteric fractures of the femur so as to provide theoretical basis for
      choosing internal fixator in clinical application. METHODS: Twelve cadaveric
      human femurs (35-50 years old) were selected with similar proximal femur,
      excluding deformities, fractures, and other lesions. The twelve femur specimens
      were randomly divided into 2 groups, 6 specimens per group. An 1 cm gap of
      osteotomy model was made in the proximal femur up to 1 cm below the lesser
      trochanter to simulate a comminuted subtrochanteric fracture of femur, and the
      distal end was embedded with denture acrylic and liquid for denture acrylic.
      Fracture was fixed by LISS in group A, and was fixed by DCS in group B. The
      specimens were fixed on Instron-8874 servo-hydraulic mechanical testing machine
      in a single-leg standing position, and the axial compression test and dynamic
      fatigue test were carried out to compare the compressive strength and the strain
      distribution at both sides of the fracture line. RESULTS: Axial compression test:
      the strain values of the 2 strain gauges in group A were significantly smaller
      than those in group B (P < 0.01); the vertical down displacement of the femoral
      head in group A was significantly smaller than that in group B (P < 0.01) under
      the same load; when the load was 600 N, the axial rigidity of group A was (209.06
      +/- 18.63) N/mm, which was significantly higher than that of group B [(65.79 +/-
      7.26) N/mm] (t = 3.787, P = 0.004). Dynamic fatigue test: the vertical down
      displacement of the femoral head in group A was significantly smaller than that
      in group B in the same cyclic loading cycle (P < 0.01); when the vertical down
      displacement of the femoral head was 0.5 mm, the force and the cyclic loading
      cycles in group A were significantly larger than those in group B (P < 0.01).
      CONCLUSION: LISS, which has good mechanical stability, can meet the requirements
      for subtrochanteric fracture of femur fixation in biomechanics and anatomical
      structures. It can be proven that the LISS internal fixator is firmer than the
      DCS internal fixator by biomechanical comparison.

PMID- 23167107
TI  - [A comparative study on effect of different defect diameters on healing in middle
      1/3 tibia monolayer cortical bone defect mouse model].
AB  - OBJECTIVE: To compare the effect of different defect diameters on healing in the
      middle 1/3 tibia monolayer cortical bone defect mouse model so as to establish an
      animal model for bone tissue engineering study, mechanism study on bone defect
      repair, and gene therapy research. METHODS: Ten 8-week-old C57BL/6J mice,
      weighing (20 +/- 2) g, were randomly divided into 2 groups, 5 mice in each group.
      The middle 1/3 tibiae monolayer cortical bone defect model of 0.8 mm (group A) or
      1.0 mm (group B) in diameter was established with burr drill. At 7, 21, and 28
      days after modeling, the molybdenum target X-ray radiography was used to observe
      the defect repair; at 28 days, Micro CT and three-dimensional imaging were used
      to evaluate bone defect repair, and tibia specimens were harvested for HE
      staining. RESULTS: At 7 days after modeling, tibia fracture occurred in 5 mice in
      group B, no fracture in group A. X-ray films, Micro CT scan, and HE staining
      showed bony union in group A at 28 days. The quantitative analysis of trabecular
      bone by Micro CT showed that trabecular number, connectivity density, and bone
      volume in group A were significantly greater than those in group B (P < 0.05),
      mean of segmented region--mean 2 was significantly less than that in group B (P <
      0.05), but no significant difference was found in trabecular separation and
      trabecular thickness between 2 groups (P > 0.05). CONCLUSION: The middle 1/3
      tibia monolayer cortical bone defect mouse model of 0.8 mm in diameter is the
      ideal animal model for study repair mechanism of tibia defect or bone tissue
      engineering.

PMID- 23167108
TI  - [Anatomical study on contralateral C7 root transfer for recovery of forearm
      flexor function in repairing of brachial plexus avulsion].
AB  - OBJECTIVE: To provide the anatomical basis of contralateral C7 root transfer for
      the recovery of the forearm flexor function. METHODS: Thirty sides of adult anti
      corrosion specimens were used to measure the length from the end of nerves
      dominating forearm flexor to the anastomotic stoma of contralateral C7 nerve when
      contralateral C7 nerve transfer was used for repair of brachial plexus lower
      trunk and medial cord injuries. The muscle and nerve branches were observed. The
      length of C7 nerve, C7 anterior division, and C7 posterior division was measured.
      RESULTS: The length of C7 nerve, anterior division, and posterior division was
      (58.8 +/- 4.2), (15.4 +/- 6.7), and (8.8 +/- 4.4) mm, respectively. The lengths
      from the anastomotic stoma to the points entering muscle were as follow: (369.4
      +/- 47.3) mm to palmaris longus, (390.5 +/- 38.8) mm (median nerve dominate) and
      (413.6 +/- 47.4) mm (anterior interosseous nerve dominate) to the flexor
      digitorum superficialis, (346.2 +/- 22.3) mm (median nerve dominate) and (408.2
      +/- 23.9) mm (anterior interosseous nerve dominate) to the flexor digitorum
      profundus of the index and the middle fingers, (344.2 +/- 27.2) mm to the flexor
      digitorum profundus of the little and the ring fingers, (392.5 +/- 29.2) mm
      (median nerve dominate) and (420.5 +/- 37.1) mm (anterior interosseous nerve
      dominate) to the flexor pollicis longus, and (548.7 +/- 30.0) mm to the starting
      point of the deep branch of ulnar nerve. The branches of the anterior
      interosseous nerve reached to the flexor hallucis longus, the deep flexor of the
      index and the middle fingers and the pronator quadratus muscle, but its branches
      reached to the flexor digitorum superficials in 5 specimens (16.7%). The branches
      of the median nerve reached to the palmaris longus and the flexor digitorum
      superficial, but its branches reached to the deep flexor of the index and the
      middle fingers in 10 specimens (33.3%) and to flexor hallucis longus in 6
      specimens (20.0%). CONCLUSION: If sural nerve graft is used, the function of the
      forearm muscles will can not be restored; shortening of humerus and one nerve
      anastomosis are good for forearm flexor to recover function in clinical.

PMID- 23167109
TI  - [Experiment study on ultrashort wave for treating vascular crisis after rat tail
      replantation].
AB  - OBJECTIVE: To explore the effect and mechanism of ultrashort wave (USW) for
      prevention and treatment of vascular crisis after rat tail replantation. METHODS:
      Eighty 3-month old female Sprague Dawley rats (weighing 232.8-289.6 g) were
      randomly divided into 5 groups. In each group, based on the caudal vein and the
      coccyx was retained, the tail was cut off. The tail artery was ligated in group
      A; the tail artery was anastomosed in groups B, C, D, and E to establish the tail
      replantation model. After surgery, the rats of group B were given normal
      management; the rats of group C were immediately given intraperitoneal injection
      (3.125 mL/kg) of diluted papaverine hydrochloride injection (1 mg/mL); the rats
      of groups D and E were immediately given the local USW treatment (once a day) at
      anastomotic site for 5 days at the dosage of 3 files and 50 mA for 20 minutes
      (group D) and 2 files and 28 mA for 20 minutes (group E). The survival rate of
      the rat tails was observed for 10 days after the tail replantation. The tail skin
      temperature difference between proximal and distal anastomosis was measured at
      pre- and post-operation; the change between postoperative and preoperative
      temperature difference was calculated. The blood plasma specimens were collected
      from the inner canthus before operation and from the tip of the tail at 8 hours
      after operation to measure the content of nitric oxide (NO). RESULTS: The
      survival rates of the rat tails were 0 (0/14), 36.4% (8/22), 57.1% (8/14), 22.2%
      (4/18), and 75.0% (9/12) in groups A, B, C, D, and E, respectively, showing
      significant overall differences among 5 groups (chi2 = 19.935, P = 0.001); the
      survival rate of group E was significantly higher than that of group B at 7 days
      (P < 0.05), but no significant difference was found between the other groups by
      pairwise comparison (P > 0.05). At preoperation, there was no significant
      difference in tail skin temperature difference among 5 groups (P > 0.05); at 8
      hours, 5 days, 6 days, and 7 days after operation, significant overall difference
      was found in the change of the skin temperature difference among groups (P <
      0.05); pairwise comparison showed significant differences after operation (P <
      0.05): group B > group D at 8 hours, group C > group D at 5 days, groups A, B,
      and C > group D at 6 days, groups B and C > groups A and E, and group B > group D
      at 7 days; but no significant difference was found between the other groups at
      the other time points (P > 0.05). Preoperative plasma NO content between each
      group had no significant difference (P > 0.05). The overall differences had
      significance in the NO content at postopoerative 8 hours and in the change of the
      NO content at pre- and post-operation among groups (P < 0.05). Significant
      differences were found by pairwise comparison (P < 0.05): group D > groups A, B,
      and C in the plasma NO content, group D > groups A and B in the change of the NO
      content at pre- and post-operation; but no significant difference was found
      between the other groups by pairwise comparison (P > 0.05). CONCLUSION: Rat tail
      replantation model in this experiment is feasible. USW therapy can increase the
      survival rate of replanted rat tails, reduce skin temperature at 7 days, improve
      blood supply, increase the content of nitric oxide at the early period and
      prevent vascular crisis.

PMID- 23167110
TI  - [Preliminary study on mechanisms of granulocyte macrophage-colony stimulating
      factor in enhancing impaired colonic anastomotic healing in rats treated with
      intraperitoneal oxaliplatin].
AB  - OBJECTIVE: To investigate the mechanisms of local application of granulocyte
      macrophage-colony stimulating factor (GM-CSF) on healing of colonic anastomoses
      impaired by intraperitoneal oxaliplatin in rats. METHODS: Sixty 10-week-old male
      Wistar rats were made the colonic anastomosis model and randomized into 3 groups,
      20 rats in each. The rats received intraperitoneal injection of 5% dextrose in
      group A, and intraperitoneal injection of 5% dextrose and 10 mL oxaliplatin (25
      mg/kg) in group B at 1 day; and 50 microg GM-CSF was injected into the
      perianastomotic area immediately after operation and 10 mL intraperitoneal
      oxaliplatin (25 mg/kg) was given at 1 day. The general situation of rats was
      observed after operation. Anastomotic healing was tested by measuring the
      bursting pressure in vivo at 2, 3, 5, 7 days. Anastomotic healing score was
      evaluated by histological staining. Immunohistochemical staining of the
      anastomotic site was used to determine the amount of collagen type I content.
      RESULTS: All animals survived to the experiment end. There was no significant
      difference in the bursting pressure among 3 groups at 2 and 3 days (P > 0.05);
      the bursting pressure of group B was significantly lower than that of groups A
      and C (P < 0.05). There was no significant difference in mononuclear cells
      infiltration, mucosal epithelialization, submucosa-muscle layer connection
      degree, and granulation tissue formation between groups A and C at different time
      points (P > 0.05); groups A and C were significantly better than group B in
      mucosal epithelialization and granulation tissue formation (P < 0.05). Groups A
      and C were significantly better than group B in mononuclear cells infiltration at
      2 and 3 days, and in submucosa-muscle layer connection degree at 5 and 7 days (P
      < 0.05). There was no significant difference in collagen type I content among 3
      groups at 2 and 3 days (P > 0.05); the content of collagen type I in groups A and
      C were significantly higher than that in group B (P < 0.05) at 5 and 7 days.
      CONCLUSION: Local administration of GM-CSF may enhance colonic anastomotic
      healing by early stimulating infiltration of macrophages and increasing collagen
      deposition.

PMID- 23167111
TI  - [Isolation and identification of regulatory T cells in peripheral blood of rhesus
      monkeys].
AB  - OBJECTIVE: To establish a method to isolate the CD4+CD25+ regulatory T cells
      (Tregs) and to identify the purity and function of these cells. METHODS: The
      peripheral blood (8 mL) were collected from the great saphenous vein of 10 rhesus
      monkeys (4 females and 6 males, aged 4-5 years, and weighing 5-8 kg). The
      mononuclear cells were isolated with density gradient centrifugation. CD4+ T
      cells were separated by the Magnetic cell sorting (MACS) negative selection and
      MACS positive selection. The cell yield rate, the cell viability, and the cell
      purity were compared between MACS negative selection and MACS positive selection.
      In CD4+ MACS negative selection, the anti-biotin MicroBeads and biotin-antibody
      cocktai in CD4+CD25+ Tregs isolation kit non-human primate were used, and in MACS
      positive selection, the anti-APC MicroBeads in CD4+CD25+ Tregs isolation kit non
      human primate and CD4-APC were used. The CD4+ T cells separated by positive
      selection were selected to obtain CD4+CD25 Tregs with CD25 MicroBeads. The
      purity, activity, the FoxP3 level, and the suppressive function to concanavalin A
      (ConA) activated autologous CD4+CD24 effective T cells (Teffs) of CD4+CD25+ Tregs
      were detected by flow cytometry. RESULTS: After CD4+ T cells were separated by
      MACS negative selection and MACS positive selection, the cell viabilities were
      all up to 95%, showing no significant difference (P > 0.05). The cell yield rate
      and purity of CD4+ T cells by positive selection were significantly higher than
      those of CD4+ T cells by negative selection (P < 0.05). CD4+CD25+ Tregs can be
      successfully isolated by MACS double positive selection. The classifying purity
      was 76.2% +/- 8.6%; the cell activity was 93.3% +/- 4.7%; and the level of FoxP3
      was 74.2% +/- 6.9%. The CD4+CD25+ Tregs had suppressive effect on ConA activated
      autologous CD4+CD25 Teffs. CONCLUSION: MACS double positive selection can be used
      to isolate high-purity CD4+CD25+ Tregs from the peripheral blood of rhesus
      monkeys and the process does not influence the activity of CD4+CD25+ Tregs.

PMID- 23167112
TI  - [Related issues in clinical translational application of adipose-derived stem
      cells].
AB  - OBJECTIVE: To introduce the related issues in the clinical translational
      application of adipose-derived stem cells (ASCs). METHODS: The latest papers were
      extensively reviewed, concerning the issues of ASCs production, management,
      transportation, use, and safety during clinical application. RESULTS: ASCs, as a
      new member of adult stem cells family, bring to wide application prospect in the
      field of regenerative medicine. Over 40 clinical trials using ASCs conducted in
      15 countries have been registered on the website (http://www.clinicaltrials.gov)
      of the National Institutes of Health (NIH), suggesting that ASCs represents a
      promising approach to future cell-based therapies. In the clinical translational
      application, the related issues included the quality control standard that
      management and production should follow, the prevention measures of pathogenic
      microorganism pollution, the requirements of enzymes and related reagent in
      separation process, possible effect of donor site, age, and sex in sampling, low
      temperature storage, product transportation, and safety. CONCLUSION: ASCs have
      the advantage of clinical translational application, much attention should be
      paid to these issues in clinical application to accelerate the clinical
      translation process.

PMID- 23167113
TI  - [Research progress of articular cartilage scaffold for tissue engineering].
AB  - OBJECTIVE: To review the research progress of articular cartilage scaffold
      materials and look into the future development prospects. METHODS: Recent
      literature about articular cartilage scaffold for tissue engineering was
      reviewed, and the results from experiments and clinical application about natural
      and synthetic scaffold materials were analyzed. RESULTS: The design of articular
      cartilage scaffold for tissue engineering is vital to articular cartilage defects
      repair. The ideal scaffold can promote the progress of the cartilage repair, but
      the scaffold materials still have their limitations. CONCLUSION: It is necessary
      to pay more attention to the research of the articular cartilage scaffold, which
      is significant to the repair of cartilage defects in the future.

PMID- 23167114
TI  - [Research progress of extracellular matrix material for tissue engineering].
AB  - OBJECTIVE: To review the current research status and clinical application
      progress of extracellular matrix (ECM) material in tissue engineering. METHODS:
      The literature about the latest progress in the preparation, biocompatibility,
      mechanical property, degradability, and clinical application of ECM material was
      extensively reviewed. RESULTS: The improvement of the ECM preparation method and
      thorough understanding of the immunological properties have laid the foundation
      for the repair and reconstruction of the tissue. Moreover, a series of animal
      studies also confirm that the feasibility and effectiveness of the ECM such as
      small intestinal submucosa, bladder ECM grift, and acellular dermis which have
      been applied to the repair and reconstruction of the urethra, bladder, arteries,
      and skin tissue. It shows a wide prospect of clinical application in the future.
      CONCLUSION: ECM material is a good bio-derived scaffold, which is expected to
      become an important source of alternative materials for the repair and
      reconstruction of the tissue.

PMID- 23167115
TI  - [Research progress of bone morphogenetic protein and liability of ossification of
      posterior longitudinal ligament].
AB  - OBJECTIVE: To review the research progress of bone morphogenetic protein (BMP)
      and the liability of ossification of the posterior longitudinal ligament (OPLL).
      METHODS: Recent literature concerning BMP and the liability of OPLL was reviewed,
      analysed, and summarized. RESULTS: The single nucleotide polymorphisms (SNPs) of
      BMP gene may produce a minor cumulative effect and increase individual
      susceptibility to OPLL. A variety of environmental factors can promote the
      occurrence and development of OPLL by increasing the expression of BMP gene.
      CONCLUSION: The SNPs of BMP gene may increase individual susceptibility to OPLL.
      However, interaction of cumulative effect of the SNPs and environmental factors
      can promote the liability to OPLL.

PMID- 23167116
TI  - [Progress in soft tissue reconstruction of adult-acquired flatfoot deformity].
AB  - OBJECTIVE: To review the progress in clinical and biomechanical study on soft
      tissue reconstruction of adult-acquired flatfoot deformity (AAFD). METHODS: The
      recent original articles of soft tissue repair and tendon transfer for AAFD were
      extensively reviewed. RESULTS: The soft tissue procedures for AAFD can be divided
      into two components: static restoration of medial column stability and dynamic
      reconstruction of the posterior tibial tendon. The most important static
      structure to be repaired for AAFD is the spring ligament. On the other hand,
      various methods can be used for dynamic reconstruction. The flexor digitorum
      longus transfer is widely used, but results of biomechanical studies do not
      support the advantage of this method. For patients having normal function of the
      posterior tibial muscle, the Cobb procedure may be more suitable. CONCLUSION: The
      soft tissue reconstruction procedures of AAFD should be chosen individually based
      on the stage and type of the deformity.

PMID- 23167117
TI  - [A confidence "pact"].

PMID- 23167118
TI  - [How to develop and increase nursing competencies from now until 2030].

PMID- 23167119
TI  - [Physician assisted suicide, four legislative bills relaunch the debate].

PMID- 23167120
TI  - [Pain and AIDS].
AB  - People suffering from AIDS, a chronic disease and a public health issue in France
      and throughout the world, present numerous forms of acute or chronic pain. This
      pain must be taken into account in the complex social-cultural environment
      specific to each patient.

PMID- 23167121
TI  - [Insulinotherapy education for children].
AB  - Functional insulinotherapy targets the reproduction of physiological insulin
      secretion in order to offer type 1 diabetic patients a better quality of life. It
      enables patients to adapt their insulin doses more accurately according to their
      diet and their lifestyle. In 2009, the multi-disciplinary team from the Chalon
      sur-Saone paediatrics department implemented a functional insulinotherapy
      therapeutic education method for diabetic children.

PMID- 23167122
TI  - [Seize the time].

PMID- 23167123
TI  - [Psychological time, definition and challenges].
AB  - Psychological time comprises different forms of time. Each form of time
      corresponds to different psychological mechanisms. The human being is subject to
      distortions of time under the effect of emotions. The effectiveness of social
      interaction depends on our aptitude to synchronise ourselves with others.

PMID- 23167124
TI  - [The question of time in the transcultural encounter].
AB  - The approach to and conception of time differ according to culture and the
      individual. In the nursing encounter, the reintroduction of human temporality
      helps those concerned to perceive the other person's time. The transcultural
      perspective demonstrates the need to take this specific time into account.

PMID- 23167125
TI  - [Time, education and nursing training].
AB  - Time is a complex reality. In education, time is a concept, a transversal aid and
      an omnipresent element. Using the past, practising in the present and
      anticipating the future are the objectives; but learning is often anchored in the
      "here and now".

PMID- 23167126
TI  - [Patient education, the time on the another side of nursing].
AB  - The law of 21st July 2009 known as the "Hospital, patients, health and
      territories" law integrates therapeutic education for the patient into the public
      health code. Patients must therefore be able to make adapted choices with regard
      to their health. Patient therapeutic education takes place at the heart of
      nursing care within a specific time for the patient and the nurse, giving rise to
      a new identity process for the nurse.

PMID- 23167127
TI  - [The announcement of a cancer diagnosis, a time of shock and urgency].
AB  - When the diagnosis of a serious illness is announced, time often seems to stop
      for the patient. However, often, that of the medical and nursing staff
      accelerates. Part of the role of the "diagnosis announcement" nurse is to connect
      the patient-time with the nursing-time.

PMID- 23167128
TI  - [A liver transplant, a specific temporal experience].
AB  - In the case of a liver transplant, the patient undergoes a particular space-time
      experience. From the announcement of the diagnosis and the prospect of death in
      the absence of a transplant, until the moment of the procedure, the nurse
      coordinator supports the patient who will experience successive times of waiting,
      hope, fear and survival.

PMID- 23167129
TI  - [Helping brain-injured patients with temporal disorientation].
AB  - Victims of a traumatic brain injury suffer from temporal disorientation. Nurses
      need to adopt innovative methods to help patients maintain the logic of day-to
      day time.

PMID- 23167130
TI  - [The perception of time in a palliative care unit].
AB  - Time is perceived differently depending on whether it is experienced by the
      patient, his or her family, friends, volunteer helpers or caregivers. It also
      differs according to the institute. In palliative care, it is still a time of
      life, accompanied to its end.

PMID- 23167131
TI  - [Time for benevolence for patients in palliative care].

PMID- 23167132
TI  - [Time in home nursing].
AB  - When a nurse cares for a patient in his or her home, she is working in the
      patient's living environment. Expected to be available and to provide high
      quality nursing care, she must organise her working time taking into account the
      patient's routine. She needs to ensure there is a good correlation between the
      nursing time and the quality of the relationship.

PMID- 23167133
TI  - [Impact of new technologies on the time for home care].

PMID- 23167134
TI  - [Resources for patient education].

PMID- 23167135
TI  - [Qualitative analysis of factors supporting the motivation for gastric bypass].
AB  - Half of Belgium's adult population is overweight and approximately 14% are obese.
      Apart from organic diseases associated with obesity, the psychological
      repercussion is very important and requires a specific caring. Conservative
      treatments containing diet, physical-activity and drugs often show limits in
      particular when the patient presents food behavioural disorders. The bariatric
      surgery is presented like an ultimate therapy. It is a specific treatment which
      involves risks and high cost for the patient. This study is based on a
      qualitative study including patients coming to a gastric bypass in order to
      appreciate the surgical indications and to describe the individual motivations
      which lead the patients to request this intervention. The study consists of semi
      structured interviews with hospitalized patients. The majority of the patients do
      not correspond to the criteria defined by the law. The psychological repercussion
      of obesity compared to the family sight and the society seems to constitute a
      crucial factor in the recourse to the gastric bypass. The motivations to undergo
      this intervention are: importance attached to the physique, need for being with
      the mode, for answering at the request of a spouse or for decreasing health
      risks. The social support of the family and friends, during and after the
      intervention is a key component of the success and the acceptability of the
      intervention. This study proposes to re-examine the criteria of access to the
      bariatric surgery and to ensure a psychological accompaniment before and after
      the intervention. That is important for patients who are badly informed about
      conditions and consequences of the intervention.

PMID- 23167136
TI  - [Magnesium in critical care and anesthesiology].
AB  - Magnesium (Mg) is an essential ion for life and is involved in many important
      biological processes. Mg deficiency may have serious consequences and has been
      implicated in many diseases. Assessment of Mg status is difficult because Mg is
      essentially intracellular and there is no simple, rapid and accurate laboratory
      test to determine total body Mg. New, non-invasive techniques are being developed
      that could be used in the near future. Mg therapy is clearly indicated in
      "torsade de pointes" and preeclampsia. Mg therapy is not recommended in the
      treatment of acute myocardial infarction, stroke or non-severe acute asthma.
      Nevertheless, Mg administration may be useful to reduce cerebral ischemic events
      after aneurysmal subarachnoid hemorrhage or in the treatment of severe acute
      asthma, specifically in children. Finally, the potential post-operative analgesic
      effect of Mg is still debated and results from new, larger clinical trials may
      help clarify this issue. This article reviews physiological functions and
      pharmacology of Mg status as well as the causes, clinical manifestations, and
      treatment of Mg deficiency. The possible analgesic effects of Mg in the
      postoperative period are also reviewed.

PMID- 23167137
TI  - [Posttraumatic stress disorder endophenotypes: several clinical dimensions for
      specific treatments].
AB  - Posttraumatic stress disorder is a syndrome with a very complex clinical that it
      is useful to describe according to a multidimensional approach. Following a
      critical review of the international literature, we have been able to highlight
      the genetic supports of posttraumatic stress disorder in the perspective of
      returning to the source of the clinical of this syndrome in order to steer its
      treatment better. We consider in succession the neuromodulation pathways
      involving dopamine, serotonine and noradrenaline to describe the
      hyperdomaminergic, hyposerotoninergic and hypernoradrenergic endophenotypes of
      posttraumatic stress disorder. Neurogenetic studies have affirmed two essential
      proposals. On the one hand, the pharmacological treatment of psychotraumatic
      disorders can be very closely adjusted to the different endophenotypes. On the
      other hand, the psychotherapeutic approach retains all its importance in the
      sense that it is the subjective implication that generated the trauma,
      subjectivity interacting with a genetic heritage and environmental factors
      integrating a social context. The changing definition of posttraumatic stress
      disorder over time comes from scientific exploration in part determined by a
      sociocultural context and, reciprocally, the psychic trauma is caused by the
      collapse of reassuring social values which were considered as immutable. The
      clinical is not developed according to fixed references: the evolution of
      neurogenetic techniques changes our perception of psychic traumas and the
      therapeutic possibilities.

PMID- 23167138
TI  - [Sexual violence in Congo-Kinshasa: necessity of decriminalizing abortion].
AB  - The sexual violence's committed in the Democratic Republic of Congo (DRC) are
      from their scales and consequences on women, real public health, politico-legal,
      and socio-economical challenges. More than a million of women have been victims
      of sexual violence on a period of less than fifteen years. Systematic rapes of
      women were used as war weapon by different groups involved in the Congolese war.
      Sexual violence against women has impacted public health by spreading sexually
      transmissible diseases including HIV/AIDS, causing unwanted pregnancies, leading
      to the gynaecological complications of rape-related injuries, and inflicting
      psychological trauma on the victims. Despite high level of unwanted pregnancies
      observed, the Congolese law is very restrictive and interdict induced abortion.
      This paper presents three arguments which plead in favour of legalizing abortion
      in DRC: 1) a restrictive law on abortion forces women to use unsafe abortion and
      increase incidence of injuries and maternal mortality ; 2) DRC has ratified the
      universal Declaration of human rights, the African union charter, and has than to
      promote equality between sexes, in this is included women reproductive rights; 3)
      an unwanted birth is an additional financial charge for a woman, a factor
      increasing poverty and psychologically unacceptable in case of rape. From the
      politico-legal point of view, ending rape impunity and decriminalizing abortion
      are recommended. Decriminalizing abortion give women choice and save victims and
      pregnant women from risks related to the pregnancy, a childbirth, or an eventual
      unsafe abortion. These risks increase the maternal mortality already high in DRC
      (between 950 and 3000 for 100000 live births).

PMID- 23167139
TI  - [Richard Doll. A surprising story of conflicts of interest].
AB  - Richard Doll is a very famous English physician epidemiologist. He is credited
      with discovering the link between smoking and lung cancer. His reputation was
      recently vitiated by two facts, ignorance of German studies prior to his work and
      the existence of major conflicts of interest with industry that led him to
      minimize the role of chemical products in carcinogenesis.

PMID- 23167140
TI  - [Medicine of the future: free choice or tyranny of proof?].

PMID- 23167141
TI  - [Several streets of the area around Brugmann Hospital received the names of
      distinguished professors of Medicine of the Universite Libre de Bruxelles].
AB  - Several streets in the area of the Brugmann Hospital in Brussels have received
      the names of distinguished professors of medicine of the Universite libre de
      Bruxelles. These physicians are: Jean-Joseph Crocq, Edouard Kufferath, Guillaume
      Rommelaere, Adrien Bayet, Leon Stienon, Albert Brachet and Jules Thiriar. In this
      short review, we resume their biography and locate their street.

PMID- 23167142
TI  - [Interpretation of electrocardiographic tracings presented at the AMUB Meeting].

PMID- 23167143
TI  - [The 13th Annual Thoracic Oncology Day].

PMID- 23167144
TI  - [Not Available].

PMID- 23167145
TI  - [Psychology in cardiac rehabilitation: where all problems emerge and should be
      solved].

PMID- 23167146
TI  - [Which diet for an effective cardiovascular prevention?].
AB  - Over the last years, numerous evidence on the existing relationship between
      nutrition and chronic degenerative diseases have led investigators to search for
      the optimal dietary pattern to maintain a good health status. It's well known, in
      fact, that nutrition is capable of substantially modifying the risk profile ofa
      subject in primary and/or secondary prevention. Several models of diet have been
      imposed on public attention, but the one that got the most interest is certainly
      the Mediterranean diet. Recently, several studies have shown that a strict
      adherence to a Mediterranean dietary pattern is associated with a lower incidence
      of mortality and incidence of chronic degenerative diseases such as
      cardiovascular disease and cancer. Meta-analyses conducted by our group have
      revealed, in a population of over than 2 million of people, that adherence to
      Mediterranean diet determines a significant reduction on the risk of
      cardiovascular and cerebrovascular accidents. To the best of the knowledge the
      most effective indications for an optimal therapeutic strategy in nutrition
      include: increase the consumption of fruits and vegetables up to the recommended
      5 servings a day, prefer whole grains, replace saturated and trans fats with
      unsaturated fats, reduce the consumption of sugar and sweetened beverages, and
      limit salt intake. With these simple indications, together with recommendations
      of following the principles of the traditional Mediterranean diet, a substantial
      reduction of the risk of incidence and/or mortality from cardiovascular disease
      can be easily obtained.

PMID- 23167147
TI  - [Endothelial progenitor cells and vascular health: effects of lifestyle's
      modifications].
AB  - During the last years increasing evidence showed that bone marrow-derived cells
      with angiogenic capability, named endothelial progenitor cells (EPCs), possess
      the capacity to home to sites of vascular injury, so contributing to the
      neoangiogenesis in vivo and to the maintenance of the homeostasis of vascular
      endothelium. Currently, potent triggers for the mobilisation of EPCs from bone
      marrow are known. In addition to some pharmacological treatment such as statins,
      erythropoietin, PPAR-gamma agonists and angiotensin-II receptor antagonists, the
      effects of healthy lifestyle, via mobilization and functional improvement of EPC,
      is increasingly recognized. In this review we analyze, the effects of lifestyle
      interventions on EPCs. In particular we will focus on physical activity and
      cardiac rehabilitation protocols, weight reduction, and smoking cessation.
      Moreover, the negative effects of depression, mood disturbances and type D
      personality on EPCs are also considered.

PMID- 23167149
TI  - [The bare minimum of information at discharge after acute coronary syndrome. Part
      1: Factors that affect communication].
AB  - Hospital discharge after an Acute Coronary Syndrome represents a potential
      pitfall for patients. Strict adherence to discharge instructions is sometimes
      essential for recovery and prevention of complications and patients' knowledge of
      diagnosis and treatment plan is an integral component of patient education.
      Discharge communication is an integral part of high-quality, patient-centered
      care but patients leaving hospital often fail to understand important elements of
      their discharge and home care plan. This paper describes the existing literature
      on patient understanding and implementation of discharge instructions, discusses
      previous interventions aimed at improving the discharge process, and recommends
      best practices.

PMID- 23167150
TI  - Smoking cessation interventions after acute coronary syndromes. Results of a
      cross-sectional survey in the Lazio Region of Italy.
AB  - Given the limited research on Italian hospital smoking care practices, a cross
      sectional survey was undertaken in April-May 2011 to describe the current status
      of smoking cessation interventions for ACS patients in cardiovascular
      institutions of the Lazio Region of Italy. Lazio is a region of central Italy
      with a resident population of about 5,600,000. According to the data of the
      Regional Health Authority, about 10.000 patients are admitted for ACS every year
      in this region of Italy. Acute cardiac care in the region is currently provided
      by 33 Cardiology Divisions. All of these units were considered as eligible for
      the survey. The eligible respondent for each unit was the director. A self-report
      questionnaire was developed based on previous studies that examined the specific
      features of smoking cessation care provided to hospitalised patients.
      Questionnaires were forwarded by the Lazio Regional Section of the Italian
      National Association of Hospital Cardiologists (ANMCO). Completed questionnaires
      were received from 22 of the 33 eligible Divisions (66%). These 22 responding
      units currently provide acute care to about 70% of all ACS patients of the
      region. Responding units were more likely to represent public non-teaching
      hospitals (p = 0.002), while non-responders were mostly from private non-teaching
      institutions (p = 0.04). Response rates were not influenced by the presence of
      either interventional catheterization laboratory (Cathlab) or cardiac surgery
      within the hospitals. The survey suggest that most of cardiology units fail to
      provide recommended smoking care interventions to ACS patients. In particular,
      brief smoking cessation advice before discharge represents the only
      systematically implemented approach in clinical practice (22 units; 100%).
      Smoking cessation counselling is provided only in 9 units (40%). Specific
      pharmacotherapy is prescribed in selected case only in about one third of units
      (7 units; 32%), with varenicline being the preferred drug. Structural variables
      and organizational complexity have no influence on smoking care, as hospitals
      with Cathlab and cardiac surgery do not implement more effective strategies.
      Overall, this survey shows that the majority of smoking ACS inpatients may
      receive inadequate smoking care and that hospitals have considerable opportunity
      for improvement.

PMID- 23167151
TI  - [Presentation of the Psycho-Cardiological schedule and convergence levels
      analyses among the psycho-cardiological screening and the psychological
      assessment].
AB  - In Cardiovascular Rehabilitation the increasing inpatients complexity suggests
      the necessity to develop screening methods which allow to identify those patients
      that require a psychological intervention. MATERIAL AND METHODS: A Psycho
      Cardiological Schedule (PCS) was developed with the aim of detecting the critical
      situation indicators or the presence of psychological, social and cognitive
      problems. The PCS, compiled by a nurse or cardiologist in collaboration with a
      psychologist, allows to assess the need for a deeper psychological examination,
      clinical and/or with tests. Aim of the present study is to identify the
      convergence levels among the observational and anamnestic data of the PCS
      collected by a nurse and the clinical and/or test data of the psychological
      deeper assessment. RESULTS: Among the 87 patients recruited in January-February
      2010, 28 (aged 53.5 +/- 12.6, M = 20, F = 8) fulfilled the criteria for a deeper
      psychological examination: age < or = 50, manifestation of
      psychological/behavioural problems, neuropsychological disorders, low adherence
      to prescriptions, inadequate disease knowledge/representation. From data
      comparisons emerged convergence levels with 100% concordance as to smoke habits
      and problems in social-family support. High convergence levels also resulted as
      to emotional and/or behavioural problems (92.8%) and inadequate adherence to
      prescriptions (89.3%). Lower levels of concordance (82.1%) emerged when
      considering disease knowledge/representation, issues specifically linked to
      cognition and subjective illness experience, not directly detectable from
      behaviour. CONCLUSIONS: our data confirm the synergic efficacy of the two
      evaluations: the Psycho-Cardiological Schedule reliably identifies the
      problematic macro-categories, mainly if they are characterized by behavioural
      indicators, which facilitate the detection. The psychological approach appears
      more suitable for better specifing macro-categories characteristics and for
      detecting critical aspects not overt but not less important, providing therefore
      advice for a therapeutic psychological management.

PMID- 23167148
TI  - [ICAROS (Italian survey on CardiAc RehabilitatiOn and Secondary prevention after
      cardiac revascularization): temporary report of the first prospective,
      longitudinal registry of the cardiac rehabilitation network GICR/IACPR].
AB  - The Italian survey on CardiAc RehabilitatiOn and Secondary prevention after
      cardiac revascularization (ICAROS) was a multicenter, prospective, longitudinal
      survey carried out by the Italian Association on Cardiovascular Prevention and
      Rehabilitation (GICR/IACPR) in patients on completion of a CR program after
      coronary artery by pass grafting (CABG) and percutaneous coronary intervention
      (PCI). The aim was to evaluate in the short and medium-term: i) the
      cardioprotective drug prescription, modification and adherence; ii) the
      achievement and maintenance of recommended lifestyle targets and risk factor
      control and their association with cardiovascular events; iii) the predictors of
      non-adherence to therapy and lifestyle recommendations. The ICAROS results offers
      a portrait of the "real world" of clinical practice concerning patients after
      CABG and PCI, and stresses the need to improve secondary prevention care after
      the index event: many patients after revascularization leave the acute wards
      without an optimal prescription of preventive medication but the prescription of
      cardiopreventive drugs and risk factors control is excellent after completion of
      a CR program. Following CR, the maintenance of evidence-based drugs and lifestyle
      adherence at one year is fairly good as far as the target goals of secondary
      prevention are concerned, but to investigate the influence of CR on long-term
      outcome longer-term studies are required. Last, but not least, ICAROS shows that
      some characteristics (PCI as index event, living alone, poor eating habits or
      smoking in young age, and old age, in particular with comorbidities) may identify
      patients with poor behavioral modification in the medium-term follow-up and in
      these patients further support may be warranted. In conclusion, participation in
      CR results in excellent treatment after revascularization, as well as a good
      lifestyle and medication adherence at 1 year and provides further confirmation of
      the the benefit of secondary prevention.

PMID- 23167152
TI  - [Measuring change in rehabilitative cardiology: reliability of a short
      questionnaire to assess an outcome].
AB  - The present Italian health planning demands the use of tools, care and treatments
      useful for the National Health Service, but with empirical effectiveness
      scientifically sustained. Aim of the present paper is to verify the validity, the
      reliability and the responsiveness of the factor "Perception of positive change"
      (named Schedule C) in cardiovascular rehabilitation. METHOD: The reliability of
      the Schedule C of the CBA VE has been examined comparing the mean scores obtained
      from each item at the entry and just before the discharge through the t-Student
      for paired sample. To assess the concurrent validity we used the AD Short Scale
      to measure anxiety and depression. 100 patients who underwent cardiac surgery
      were enrolled during hospitalization for a Cardiac Rehabilitation Programme.
      Cronbach's alpha was used to assess internal consistency of each item. RESULTS:
      Each item of the Schedule C demonstrated good internal consistency (Cronbach
      Alpha > .88) and elevated correlations item-total for each item. The strong
      correlation of anxiety and depression scores with the Schedule C points out
      appropriate concurrent validation. CONCLUSIONS: We believe that the Schedule C of
      the CBA VE is endowed with suitable metric validity and then useful as outcome
      evaluation in cardiovascular rehabilitation settings.

PMID- 23167153
TI  - Long-term treatment with high-dose of sildenafil in a thalassemic patient with
      pulmonary hypertension.
AB  - We report a case of a 37-years-old man, affected by thalassemia major,
      hypogonadotropic hypogonadism, chronic HCV-hepatitis, diabetes mellitus, severe
      osteoporosis, prior septic pulmonary embolism and pulmonary artery hypertension
      was performed a long-term treatment with high-dose of sildenafil (120 mg/die)
      with reduction of pulmonary arterial systolic pressure and of the dyspnea.

PMID- 23167154
TI  - Infective endocarditis or myxoma? Description of a patient with new diagnosis of
      congestive heart failure.
AB  - Infective endocarditis (IE) is an inflammatory disease which interests heart
      endothelium and mostly heart valves. IE is not a uniform disease, but presents in
      a variety of different forms that makes the diagnosis difficult. Echocardiography
      is a crucial diagnostic tool for the diagnosis, especially in those patients who
      have no typical symptoms as in the case here presented, in which the possibility
      of a myxoma was also considered.

PMID- 23167155
TI  - Early cardiac resynchronization therapy (CRT) improves the outcome in heart
      failure (HF) patients with left bundle branch block (LBBB).

PMID- 23167156
TI  - [Image of the month. Abnormal gluteal crease revealing Currarino syndrome].

PMID- 23167157
TI  - [Clinical case of the month. Spontaneous hematoma and acquired hemophilia].
AB  - Acquired haemophilia is a rare disease, 50% of the cases are idiopathic. We
      report a case admitted in cardiology for spontaneous hematoma. Observation of
      isolated prolonged activated partial thromboplastin time (aPPT) without
      anticoagulation treatment and the absence of correction with normal plasma
      suggested diagnosis. Confirmation of inhibitors to FVIII allowed perfusions of
      activated prothrombin complex concentrates.

PMID- 23167158
TI  - [Clinical case of the month. Left recurrent neck abscess revealing a fourth
      branchial cleft fistula].
AB  - The fourth branchial cleft fistula, which can be the origin of a recurrent left
      neck abscess, is a rare congenital malformation. Its diagnosis can be difficult.
      A ten-year-old girl presented with a left painful swelling of the neck. At
      ultrasonography and tomodensitometry, the diagnosis of thyroglossal cyst was
      suspected. Antibiotics were prescribed before surgical resection. The
      intervention was successful and the peroperative macroscopic aspect of the lesion
      suggested a dermoid cyst. Four months later, the same symptoms reappeared with
      fever. An intravenous antibiotic therapy was started while a magnetic resonance
      imaging demonstrated a possible aero-digestive tract fistula. Two days later, the
      patient developed an aero-cutaneous fistula. Oral antibiotics were started. Five
      months later, the girl came back for a second recurrence. A few days after her
      admission, she developed again an aero-cutaneous fistula. The diagnosis of
      surinfected fourth cleft fistula was made. An antibiotic therapy was started
      until the second intervention. After discussion about embryology, we describe the
      physiopathology, the differential diagnosis and the management of a fourth
      branchial cleft fistula causing recurrent left neck abscess.

PMID- 23167159
TI  - [2011 European guidelines for the management of cardiovascular diseases during
      pregnancy. Part II: management of hypertension].
AB  - In this article, we report the 2011 European guidelines on the management of
      cardiovascular diseases during pregnancy, with particular attention to the
      management of hypertension as hypertensive disorders are the most frequent
      cardiovascular complications in pregnancy.

PMID- 23167160
TI  - [Two bacteria and common skin infections].
AB  - Common bacterial skin infections represent frequent disorders encountered in
      general practice and in dermatology as well. They encompass a series of
      infections affecting the epidermis, dermis, hypodermis and subcutaneous tissues.
      The two main bacteria involved in these processes are Streptococcus pyogenes and
      Staphylococcus aureus. The resulting infections show various clinical
      presentations. Their management must be adapted to their gravity and to the
      putative or proven nature of the causal microorganism. Searching for any skin
      ingress possibility and any favouring factor is always of importance in order to
      stimulate healing and avoid recurrences. Of note, skin possibly allows the
      ingress way for a secondary septicemic dissemination. Conversely, skin is
      possibly involved in tissue localisation of septicemia.

PMID- 23167161
TI  - [Use of oral oxybutynin at 7.5 mg per day in primary hyperhidrosis].
AB  - Oxybutynin is being increasingly being prescribed in the treatment of
      hyperhidrosis but currently, there is no precise dosage for this treatment. Nine
      patients were treated for primary hyperhidrosis resistant to conventional
      therapies with oxybutynin between January to May 2010. The treatment was
      progressively increased at 7.5 mg per day. Oxybutynin efficacy was evaluated by
      iodine starch test and biometrological measurements at 2 and 4 weeks of
      treatment. Hyperhidrosis Disease Severity Scale (HDSS) and Dermatology Life
      Quality Index (DLQI) were obtained for each patient. The means of HDSS and DLQI
      were respectively 3.2 +/- 0.7 and 17.0 +/- 5.1 before treatment and were 1.8 +/-
      0.4 and 4.6 +/- 4.4 at 4 weeks of treatment. Oxybutynin at 7.5 mg per day
      significantly decreased intensity and area of sweat for palms but not for soles.
      Trans Epidermal Water Loss, conductance, pH and Skin temperature were modified
      with treatment. Oxybutynin at 7.5 mg per day has improved patient's quality of
      life. Efficiency of oxybutynin in primary palmar hyperhidrosis was proved by
      biometrological measurements and iodine starch test.

PMID- 23167162
TI  - [Wellens syndrome: a poorly known yet significant electrocardiographic entity].
AB  - We report the case of a 54-year-old patient admitted to an emergency department,
      because of a thoracic pain suspicious for angina pectoris. Although the patient
      had become asymptomatic on admission, his electrocardiogram presented
      abnormalities (biphasic T waves in V1 to V4 ) which prompted a diagnosis of
      unstable angina.This electrocardiophic pattern is known as Wellens' syndrome.

PMID- 23167163
TI  - [Nodular focal hyperplasia in a child].
AB  - We report the case of seven year old girl, suffering from Steinert's disease and
      developing a nodular focal hyperplasia. The latter was fortuitously discovered on
      the occasion of an echography performed during the follow up of a post
      catheterisation umbiblical vein hematoma. The lesion increased and became
      symptomatic. Nodular focal hyperplasia is a rare pathology in a child of that age
      and can be treated differently than in adults.

PMID- 23167164
TI  - [Variations of time perspective by social deprivation, what are the effects on
      smoking cessation?].
AB  - Smoking represents a major public health problem because of its high morbidity
      and mortality rates. Nearly half of the deaths in the lower class are caused by
      smoking. The socially deprived are physically and psychologically vulnerable. The
      instability of their situation increases the difficulty to invest in smoking
      cessation and certain time orientations linked to this social deprivation
      represent negative factors in the prognosis. Socially deprived populations do not
      understand the consequences of smoking unless they are in denial of the risks.
      The motivation to stop is essentially financial. The perception of smoking
      cessation is taken as a deprivation of pleasure. Independently of the social
      deprivation factors, taking into account the time perspective conveys necessary
      information of appropriate care.

PMID- 23167165
TI  - [Thoracic ultrasound: the pneumologist's new stethoscope].
AB  - We now have access to a large library of publications validating transparietal
      thoracic echography in various clinical situations. Parietal lesions, including
      osteolysis, can be detected and biopsied during the thoracic ultrasound (TUS)
      examination. To evaluate the parietal extension of lung cancers, TUS has proved
      superior to tomodensitometry. Pleural effusions can be easily diagnosed and
      aspirated. Pneumothoraces can be detected using well defined lung artifacts with
      a high frequency probe. Pleural and peripheral lung nodules can be detected and
      biopsied with real time visualization; the procedure is safe and accurate. Lung
      consolidations with a pleural contact can be diagnosed; this is particularly
      useful for pregnant women. In conclusion, TUS is a precious diagnostic tool for
      chosen applications, and can help to guide interventional procedures. The
      portable devices are also very useful for bedridden patients or for out of
      hospital use.

PMID- 23167166
TI  - [Free fat transfer--a versatile tool in reconstructive surgery].
AB  - Free fat transfer or lipofilling is a procedure quickly increasing in popularity.
      Free fat transfer offers treatment for soft tissue defects caused by trauma or
      cancer, congenital anomalies, painful scars, irradiation injuries and aesthetic
      indications. The advantages compared to, e.g., traditional flap reconstructions
      includes surgical easiness, minor donor-site morbidity, easy access, hardly no
      scars, quick recovery and avoidance of foreign bodies such as implants. The
      regenerative potential of free fat transfer is due to abundant adipose derived
      mesenchymal stem cells (ADSC). These cells are under extremely active
      investigation and have rapidly led to clinical trials and treatment modalities in
      combination with tissue engineering. Free fat transfer nowadays offers hope to
      patients that formerly could not be helped with surgical intervention.

PMID- 23167167
TI  - [Nanoscale tailoring of the surface properties of biomaterials and drug
      carriers].
AB  - Functionalities of biomaterials and drug delivery systems are improved by
      tailoring their surface properties using modern nanotechnology. Orthopedic
      implants and invasive electrodes are examples of implantable biomaterials.
      Biological interactions of orthopedic implants can be optimized by the synergetic
      effect of surface micro- and nanotexturing with a chemical composition of
      coating. Further, mechanical flexibility and electrochemical characteristics of
      invasive electrodes are improved by using micro- and nanotechnology. In nano-size
      drug delivery systems, surface properties of nanocarriers strongly affect their
      safety and efficacy. Mesoporous silicon nanoparticles are example of nanocarriers
      those properties can be tailored for drug delivery applications.

PMID- 23167168
TI  - [Foley catheter versus intravaginal misoprostol for labour induction].
AB  - BACKGROUND: Both mechanical and pharmacological methods are used for induction of
      labour. AIM OF THE STUDY: To compare the effectiveness and safety of induction of
      labour with Foley catheter vs. vaginal administration of misoprostol
      prostaglandin. MATERIAL AND METHODS: Obstetric data of 235 women with induced
      labour (142 with Foley catheter and 213 with misoprostol) were collected from
      medical records. RESULTS: There were no differences in frequency of caesarean
      section or in the rate of neonatal complications between the two groups. Oxytocin
      was used more frequently among nulliparous women in the Foley group. CONCLUSIONS:
      Labour induction with Foley catheter is as safe and effective as induction with
      misoprostol.

PMID- 23167169
TI  - [Update on current care guidelines: knee and hip osteoarthriti].
AB  - The goal of OA (osteoarthritis) treatment is to relieve pain and maintain/improve
      patient's functional capacity. First line medication is paracetamol and topical
      NSAIDs, and oral NSAIDs when needed. Tramadol and codeine may be considered in
      most severe cases. Glucosamine and chondroitin do not differ from placebo, but
      intra-articular glucocorticoids and hyaluronate may be useful. Supervised
      exercise is recommended especially for knee osteoarthritis. Cold, TENS and
      ultrasound therapies may offer short-term benefits in knee OA. Arthroscopic
      debridement does not alleviate OA symptoms. Arthroplasty is indicated if pain is
      not otherwise manageable.

PMID- 23167170
TI  - [Being prepared for acute poisonings in occupational health services].
AB  - Workplaces in which chemicals are used, should assess and be prepared for the
      risk of accidents due to the use of chemicals. The most common chemicals causing
      a risk of poisoning include various acids and bases, gases and vapors irritating
      the airways as well as systemically toxic gases and vapors such as carbon
      monoxide, hydrogen cyanide and hydrogen sulfide. Antidotes that can be given to
      the victim of poisoning at the workplace are available for a very limited number
      of industrial chemicals. First aid and treatment are therefore often symptomatic.

PMID- 23167171
TI  - [Surrogate alcohol poisonings].
AB  - Surrogate alcohols, i.e., methanol, ethylene glycol and isopropanol, still cause
      some dozens of deaths in Finland every year. Assessment of the severity of the
      intoxication is often hampered by the presence of ethanol. If ingestion of
      surrogate alcohol is suspected and the patient is diagnosed with metabolic
      acidosis, treatment should be initiated immediately, without waiting for the
      result of concentration analysis. Ethanol is commonly utilized as an antidote in
      Finland, whereas the use of a specific antidote, fomepizole, is slowly
      increasing. Reversal of acidosis and hemodialysis are also essential measures in
      the treatment of methanol and ethylene glycol poisoning.

PMID- 23167172
TI  - [Poisonings and their treatment during pregnancy].
AB  - In poisonings during pregnancy, the mother should be treated as well as possible,
      following the general principles and regimes utilized in treatments for
      poisoning. Activated charcoal can be used safely. In cases where administration
      of antidote is justified from the mother's standpoint, it can also be given to a
      pregnant mother. Risk assessment for poisonings during pregnancy can be difficult
      in individual cases. Fetal prognosis is, however, relatively good provided that
      the mother receives appropriate and timely initiated treatment.

PMID- 23167173
TI  - [Extracorporeal blood purification for poisonings].
AB  - Most poisonings that have resulted in hospitalization in Finland are alcohol,
      drug or mixed poisonings of adults. If the quantity of the drug or the poison is
      high or organ injury is anticipated, the patients may require extracorporeal
      blood purification in order to eliminate the substance or its metabolic products
      from the circulation. Hemodialysis or hemodiafiltration are used as the
      treatment, if the substance having caused the poisoning is water-soluble, binds
      to proteins only to a small extent, and has a low molecular weight and small
      distribution of volume. Fat-soluble substances are eliminated by using
      hemoperfusion, those having bound to proteins by using albumin dialysis.

PMID- 23167174
TI  - [Antidotes--often expensive and not always available].
AB  - While there is seldom need for most anti-poisoning agents and antidotes, they
      should be quickly available, when needed. Local worst-case scenarios, regional
      staggering of the treatment, and distances must be taken into account at the
      health care unit level. Hospitals are fairly well equipped with the recommended
      antidotes. Replenishment of the stocks is complicated by continual disruptions in
      supply of antidotes. New antidotes in the updated recommendation include calcium
      folinate (leucovorin) for methanol poisoning and octreotide for the treatment of
      hypoglycemia caused by intoxications resulting from antidiabetics of the sulfonyl
      urea group.

PMID- 23167175
TI  - [Compare the results of supracricoid partial laryngectomy-cricohyoidopexy and
      horizontal-vertical hemilaryngectomy in the treatment of mid and late laryngeal
      carcinoma].
AB  - OBJECTIVE: To compare the results of supracricoid partial laryngectomy
      cricohyoidopexy (SCPL-CHP) and horizontal-vertical hemilaryngectomy in the
      treatment of mid and late laryngeal carcinoma. METHOD: Retrospective analysis on
      the types of mid and late stage of laryngeal carcinoma clinical material, 22
      patients supracricoid partial laryngectomy-cricohyoidopexy, 20 patients
      horizontal-vertical hemilaryngectomy, each with the added radiotherapy. The long
      term results of operation and glottic reconstruction were evaluated by
      postoperative visiting, semi-quantitative speech intelligibility analysis,
      electroglottograph (EGG) and so on. RESULT: Forty-two cases of laryngeal cancer
      patients were decannulated, the decannulation rate was 100%. Postoperative
      decannulation time: surgical CHP for (44.0 +/- 4.6) d, 3/4 throat operation for
      (39.0 +/- 2.7) d, two groups of postoperative decannulation time difference was
      statistically significant (t = 4.2395, P < 0.01). Eight weeks after evaluation,
      two groups's swallowing function and postoperative evaluation of patients after
      one year speech intelligibility difference was not statistically significant (P >
      0.05). GRBAS in the evaluation of G rating, the difference between the two groups
      was statistically significant (P < 0.05), CHP group showed,for most patients, a
      severe hoarse degree, but 3/4 throat operation group mainly represented a
      moderate degree lever. EGG parameters were checked after 1 years. F0 comparative
      differences was not statistically significant (P > 0.05), and the jitter, shimmer
      and NNE compared CHP group to 3/4 laryngectomy group were significantly increased
      (P < 0.05). Kaplan-Meier method statistics show: CHP group and 3/4 laryngectomy
      group 3 years and 5 year accumulate survival rates were 95.5% and 89.7%, 85.1%
      and 83.7% respectively, two groups of three, five years of survival difference
      was not statistically significant (P > 0.05). CONCLUSION: According to the
      laryngeal of middle-late carcinoma, the region and the involvement of the scope
      were considered to choose appropriate surgical treatments, and both can complete
      resection of the tumor, and can retain good laryngeal functions,and CHP has a
      wider range of operation indications and clinical application prospect, is worthy
      to be popularized.

PMID- 23167176
TI  - [Clinical analysis of granulomatous capillary hemangioma of the larynx].
AB  - OBJECTIVE: To improve the acknowledgement of clinician on granulomatous capillary
      hemangioma of the larynx. METHOD: Collect patients in our hospital who were
      treated with granulomatous capillary hemangioma of the larynx from 2006 to 2011
      and the clinical data, treatment and follow-up consequence were retrospectively
      analyzed. RESULT: There are 10 cases of laryngeal granulomatous capillary. Eight
      patients with hoarseness as the chief complaint, in the eight patients three
      cases associated with foreign body sensation in the throat. One patient with
      hemoptysis as the main performance. The left one patient to hospital because of
      pharyngeal foreign body sensation associated with blood in the sputum. All were
      treated with surgery, there are several cases supplemented by CO2 laser
      treatment, so far no case of postoperative recurrence. CONCLUSION: Granulomatous
      capillary hemangioma is a benign, vascular proliferation of the skin or mucosa,
      rather than ture tumor. Recurrence is rare if completely excised. The prognosis
      is encouraging.

PMID- 23167177
TI  - [Exploration of screening scores for pediatric obstructive sleep apnea hypopnea
      syndrome].
AB  - OBJECTIVE: To evaluate the feasibility of screening for pediatric obstructive
      sleep apnea hypopnea syndrome (OSAHS) according to OSA-18,physical examination
      and electronic nasopharyngoscopy. METHOD: Outpatients with snoring received
      questionnaire, physical examination and electronic nasopharyngoscopy in Pediatric
      Sleep Center of Beijing Children's Hospital from 2009.1 to 2009.12. All children
      were divided into OSAHS or non-OSAHS group based on the results of
      polysomnography (PSG). The material was compared between these two groups.
      RESULT: The differences of age,tonsil scores, adenoid scores,total OSA-18 sores,
      the loudness of snoring scores, sleep asthma or suffocation scores, worrying lack
      of oxygen scores were significant (P < 0.05). And then put them into the logistic
      equation Y and make ROC analysis, if Y is higher than 0. 735, these children were
      more likely with OSAHS. The sensitivity was 62.7% and the specificity was 79.4%.
      CONCLUSION: It is feasible to screen for pediatric OSAHS according to
      questionnaire, physical examination and electronic nasopharyngoscopy.

PMID- 23167178
TI  - [Low-temperature plasma assisted via mouth for surgery treating styloid process
      syndrome].
AB  - OBJECTIVE: To compare the low-temperature plasma assisted way and the traditional
      method in surgery treating styloid process syndrome. METHOD: The clinical data
      from 23 patients who have a typical syndrome and need surgery treating, thirteen
      patients had been treated by low-temperature plasma way and the left cases by
      traditional one. Comparing operation time, amount of bleeding, degree of
      pain,time of the fake membrane falling and effort estimating. RESULT: The
      difference of operation time,amount of bleeding and degree of pain between low
      temperature plasma and tradition in the two operation procedures is significant
      (P < 0.01). But time of the fake membrane falling and effort estimating of low
      temperature plasma and traditional procedures are found to be similar (P > 0.05).
      And one patient who used the traditional operation bled when he was at home.
      CONCLUSION: The two operation procedures are both effective. The low-temperature
      plasma assisted via mouth for surgery treating elongated styloid process has a
      big advantage in operation time, amount of bleeding and degree of pain. For the
      more, it reserves the function and morphology of tonsil; which is more simple,
      convenient, safe and tiny wound.

PMID- 23167179
TI  - [The relationship between pleomorphic adenocarcinoma and dermatomyositis (with a
      case report and review of the literatures)].
AB  - OBJECTIVE: The purpose of this article is to improve the understanding of
      complications of pleomorphic adenocarcinoma, and the possibility of complicated
      with dermatomyositis. In order to explore whether there is a certain relationship
      between the two diseases. METHOD: Reported one patient in our hospital with the
      diagnosis of pleomorphic adenocarcinoma complicated dermatomyositis, and
      clarified the diagnosis and treatment of these two diseases during
      hospitalization. Reviewed the latest clinical literature relevant to pleomorphic
      adenocarcinoma and dermatomyositis. RESULT: The patients underwent superficial
      parotidectomy treatment. The postoperation pathologic and immunohistochemical
      examination confirmed the diagnosis of pleomorphic adenocarcinoma.
      Dermatomyositis improved better after the operation. CONCLUSION: Pleomorphic
      adenocarcinoma has the possibility of complicated with dermatomyositis which may
      misdiagnosis in clinical practice. Summarize the latest diagnosis progress of
      pleomorphic adenocarcinoma and the surgical treatment of the tumor. Also discuss
      the standards of clinical diagnosis and treatment of dermatomyositis. Analysis
      there may be a relationship between the two diseases on autoimmune mechanism.

PMID- 23167180
TI  - [Jinsangsanjie capsule for treating vocal fold polyps and vocal nodules].
AB  - OBJECTIVE: To investigate therapeutic effects of Jinsangsanjie capsule on vocal
      fold polyps and vocal nodules. METHOD: Seventy-five patients with vocal fold
      polyps and vocal nodules were treated by taking Jinsangsanjie capsule orally.
      After the therapeutic course, they were all followed up for 1 month. RESULT: The
      effective rate of vocal nodule group was 93.8%, the effective rate of vocal fold
      polyp group was 89.7%, the effective rate of vocal nodule with acute congestion
      group was 100%, the effective rate of vocal fold polyp with acute congestion
      group was 100%, and the effective rate of hypertrophy of vocal cords with chronic
      congestion group was 66.7%. CONCLUSION: Jinsangsanjie capsule has definite
      efficacy for treatment of vocal fold polyps and vocal nodules and deserved to be
      recommended.

PMID- 23167181
TI  - [Surgery added with fluconazole in treatment of fungal rhinosinusitis].
AB  - OBJECTIVE: To explore the effect of surgery added with antifungal agents in
      treatment of fungal rhinosinusitis. METHOD: One hundred and two consecutive
      patients with fungal rhinosinusitis were randomly divided into two groups: the
      control group (n=48) were treated with surgery alone, the treatment group (n=54)
      were treated with surgery plus antifungal therapy during operation and
      postoperation. The patients were followed up for 6 months and the relapse rates
      between two groups were compared. RESULT: No relapse was observed in the
      treatment group. The relapse rate of the control group was 20.8% (P < 0.01).
      CONCLUSION: Surgery plus antifungal therapy can prevent the relapse of fungal
      rhinosinusitis significantly.

PMID- 23167182
TI  - [Preliminary investigation of low-temperature radiofrequency ablation on
      treatment of tongue base cyst].
AB  - OBJECTIVE: To explore the feasibility of low-temperature radiofrequency ablation
      for the treatment of tongue base cyst. METHOD: Low-temperature radiofrequency
      ablation was used to treat 14 patients with the cyst of tongue base under general
      anesthesia with endotracheal intubation. Operation time, the volume of blood loss
      and postoperative complications were recorded and the follow-up was taken after
      surgery. RESULT: The tongue base cysts were totally resected in 14 patients,
      among which 12 patients only underwent one operation under general anesthesia and
      two patients received once again under local anesthesia. The procedure took
      approximately 5-10 min and the volume of blood loss during surgery varied from 1
      5 ml. Endotracheal catheter was extubated as usual and incision of trachea was
      not done. The VAS score of foreign pharynx sensation decreased significantly from
      preoperative 83.1 +/- 11.2 to postoperative 10.3 +/- 3.6 (P < 0.01). There were
      no significant postoperative haemorrhage, pharyngalgia, dyspnea or other
      complications. Speech and the motor function of tongue base were not affected.
      Follow-up survey ranged from 7 months to 3 years and the cure rate was about
      92.9% (13/14) as the recurrence occurred only in one out of 14 cases. CONCLUSION:
      Low-temperature radiofrequency ablation is a promising management for the cyst of
      tongue base with less trauma, complications or recurrence.

PMID- 23167183
TI  - [Effects of EGCG on the nasopharyngeal carcinoma cell line CNE-2 and the
      expression of related gene].
AB  - OBJECTIVE: To study the effects of epigallocatechin-3-gallate (EGCG) on
      proliferation and apoptosis of nasopharyngeal carcinoma CNE-2 cell line and
      analyze the expression of Bcl-2, Bax and Caspase-3 in the cell line which treated
      with EGCG. METHOD: MTT assay and flow cytometry were used to analyze cell
      proliferation and cell cycle. Hoechst33258 fluorescence staining was adopted to
      study cell apoptosis. RT-PCR was used to detect the expression of Bcl-2, Bax,
      Caspase-3. RESULT: EGCG could significantly inhibit proliferation of CNE-2 cell
      line and induce its apoptosis with dose-independent relationship. EGCG could
      suppress the expression of Bcl-2 and induce expression of Bax, Caspase-3.
      CONCLUSION: EGCG in vitro has efficacy of anti-nasopharyngeal carcinoma cells,
      which may be through regulating the expression of cell proliferation and
      apoptosis genes involved.

PMID- 23167184
TI  - [The study of expression of BRMS1 gene protein and the expression of BRMS1 gene
      promotor area methylation in supraglottic laryngeal carcinoma and its clinical
      significance].
AB  - OBJECTIVE: To investigate the expression of breast cancer metastasis suppressor 1
      (BRMS1) gene protein and the expression of BRMS1 gene promotor area methylation
      in supraglottic cancer and to evaluate its clinical significance. METHOD: The
      expression of BRMS1 protein and BRMS1 gene promotor area methylation were
      examined by using Western blotting method and methylation-specific polymerase
      chain reaction(MSP) method in 70 cases of supraglottic cancer tissues and 60
      cases of their surrounding laryngeal normal mucosa tissues (LNT) and 44 cases of
      cervical lymph node metastasis of supraglottic cancer. RESULT: Western blot
      results indicate that BRMS1 protein expression is declined expression level in
      supraglottic cancer tissue than the expression of BRMS1 protein in LNT of
      supraglottic cancer. Compared with para carcinoma normal laryngeal mucous tissue,
      BRMS1 gene protein in supraglottic cancer tissue primary lesion decreased
      obviously, and it is decreased more obviously in cervical lymph node metastasis
      lesion, the discrepancy is notable (P < 0.05). MSP results indicate BRMS1 gene
      promotor methylation is coordinated with its down-expression in supraglottic
      cancer tissue. BRMS1 promotor area methylation analysis reveal that there were 34
      patients with methylation in 70 patients' supraglottic cancer tumor primary
      lesion, hold 48.6% (34/70); 32 patients have methylation in 44 patients' cervical
      metastasis lymph node tissue, hold 72.7% (32/44); however, there is no
      methylation in 60 para carcinoma tissue (r(s) = 0.66, P < 0.05). CONCLUSION: The
      expression of BRMS1 protein in supraglottic cancer is significantly decreased. It
      had correlation with clinical stage and pathologic differentiation and cervical
      lymph node metastasis of supraglottic cancer. BRMS1 gene promotor methylation is
      related with down-expression of BRMS1 gene protein of supraglottic cancer. Maybe
      BRMS1 gene promotor methylation is one of the reasons of its down-expression.

PMID- 23167185
TI  - [Analysis on expression of survivin and PTEN in vocal cords polyps, papilloma of
      larynx and laryngeal squamous cell carcinoma].
AB  - OBJECTIVE: Through exploring the differentiation on positive expressing rates
      between oncogene survivin and tumor-suppressor gene PTEN (phosphatase and tensin
      homolog deleted on chromosome ten) on vocal cord polyps (VCP), adult type
      laryngeal papilloma (ALP), and laryngeal squamous cell carcinoma (LSCC), to
      reveal the mechanism in cancellation of human laryngeal squamous cells, from
      benign proliferative lesion, benign tumor to malignant tumor in larynx. METHOD:
      After picking out 18 cases of VCP, 10 cases of ALP, and 18 cases of LSCC for
      immunohistochemical process of Survivin and PTEN with two continuous section
      preparations, the differentiations of positive expression rates of Survivin and
      PTEN in the same human laryngeal squamous cells areas among three diseases were
      compared. RESULT: The positive expressing rates of survivin and PTEN in VCP were
      obviously more lower than in ALP and LSCC (P < 0.05), which showed no obvious
      difference between each other(P > 0.05). The positive expressing rates of
      survivin were always higher than PTEN in VCP, ALP and LSCC evidently (P < 0.05).
      CONCLUSION: PTEN, expressing for competition purpose, shows a subordinative
      relationship with Survivin. Although they have opposite functions in determine
      whether the cancellation of laryngeal squamous cells take place or not, Survivin
      is always playing the leading role and making predominant impact on development
      of benign proliferative lesion, benign and malignant tumor in larynx.

PMID- 23167186
TI  - [Combined treatments on sinuous mucosa after endoscopic sinus surgery and
      preliminary observation on the mucosa vesting].

PMID- 23167187
TI  - [Inflammatory myofibroblastic tumor of larynx: one case report].
AB  - Hoarseness, associated with a pharyngeal abnormal sensation, intermittent cough,
      without the symptoms of bloody sputum, dyspnea, fever, fatigue, weight loss and
      other symptoms. No lymphadenectasis or other abnormal symptoms. Routine tests,
      just like blood and urine routine, liver and kidney function, blood coagulation
      routine, ECG, chest radiograph, no abnormal results.

PMID- 23167188
TI  - [Combined airway disease].
AB  - The datas of epidemiological, clinical, and immunopathology demonstrate there is
      an important link between upper and lower airways. The upper airways diseases
      including the allergy rhinitis, the professional rhinitis, the sleep apnea and
      hypoventilation syndrome, nose polyposis (with/without aspirin sensitive), the
      chronic rhinosinusitis and so on, have an important contacting with lower airways
      diseases. Understanding how the upper airway does affect the lower airway
      disease, has the influential role to diagnosis, the treatment and the prognosis.
      This article made the brief summary on the important relation about among the
      nose, the paranasal sinus and the lung recent years.

PMID- 23167189
TI  - [Present research on the status and the prospect of insulin-like growth factor-I
      in head and neck cancer].
AB  - Insulin-like growth factor-I (IGF-I) is a multifunctional cell regulating factor,
      which plays an important role in the normal physiological activities and
      pathological process, This article reviewed the research status of the molecular
      structure of IGF- I and its regulatory factors, the molecular biological role of
      IGF- I in cell proliferation, cell motility, apoptosis, and reviewed the
      important role of IGF-I in head and neck tumor, as well as put forward the
      prospects of IGF-I in middle ear cholesteatoma pathogenesis.

PMID- 23167190
TI  - [Design and application of high-throughput screening tools: a review].
AB  - As an efficient and promising protein engineering strategy, directed evolution
      includes the construction of mutant libraries and screening of desirable mutants.
      A rapid and high-throughput screening method has played a critical role in the
      successful application of directed evolution strategy. We reviewed several high
      throughput screening tools which have great potential to be applied in directed
      evolution. The development of powerful high-throughput screening tools will make
      great contributions to the advancement of protein engineering.

PMID- 23167191
TI  - [Overview on duck virus hepatitis A].
AB  - This article describes the nomenclature, history and genetic evolution of duck
      hepatitis A virus, and updates the epidemiology, clinical symptom and
      surveillances of duck virus hepatitis A. It also summarizes the present status
      and progress of duck virus hepatitis A and illustrated the necessity and urgency
      of its research, which provides rationale for the control of duck hepatitis A
      virus disease in China.

PMID- 23167192
TI  - [Research progress in glucose-6-phosphate dehydrogenase in higher plants].
AB  - Glucose-6-phosphate dehydrogenase (G6PDH) catalyzes the first and rate-limiting
      step of the oxidative pentose phosphate pathway, existing in both cytosolic and
      plastidic compartments of higher plants. Its main function is to provide reducing
      power (NADPH) and pentose phosphates for reductive biosynthesis and maintenance
      of the redox state of the cell. In addition, the expression of this enzyme is
      related to different biotic and abiotic stresses. In this review, we analyzed the
      isoenzyme, regulation and biological function of G6PDH. Meanwhile, we summarized
      the progress work of G6PDH involved in stress resistance, gene cloning, enzyme
      deficiency and cluster analysis. Problems should be solved were also discussed.

PMID- 23167193
TI  - [Cloning and characterization of a thermostable urate oxidase from Microbacterium
      sp. strain ZZJ4-1].
AB  - In order to characterize a thermostable urate oxidase (Uox) from Microbacterium
      sp. strain ZZJ4-1, we cloned its gene (uox). The open reading frame of uox
      contained 894 base pairs and encoded a protein with 297 amino acids. Alignment of
      gene sequences indicated there was no obvious identity with the most reported uox
      and that 72% identity was found with uox from Arthrobacter globiformis. We
      inserted the gene into the plasmid pET-15b to construct an expression vector pET
      15b-uox and got it induced expression in Escherichia coli BL21 (DE3). After the
      purification of the recombinant Uox by the HisBind column, we studied some
      properties of it. It was composed of subunits with a molecular mass of about 35
      kDa. The optimal temperature and pH was 30 degrees C and pH 7.5. It was stable
      below 65 degrees C and from pH 8.5 to 11.0. The Km value was 0.22 mmol/L with the
      uric acid as the substrate. Ag+, Zn2+, CU2+ and SDS could totally inhibit its
      activity while Tween 20, Tween 80 and Triton X-100 had a slight promotion effect.
      The thermal stability of this enzyme was the most excellent among the reported
      recombinant Uox. Based on this property, it would be very useful in the
      application.

PMID- 23167194
TI  - [Lycopene synthesis via tri-cistronic expression of LeGGPS2, LePSY1 and crtI in
      Escherichia coli].
AB  - Studies on lycopene synthesis in Escherichia coli were not only able to gain the
      strains with high yield and less by-products, but also able to test functions of
      genes or gene clusters. In this article, the cDNA sequences of tomato LeGGPS2 and
      LePSY1 as well as the coding sequence of crtI from Erwinia uredovora, each of
      which was added a ribosome biding site, were controlled by T7 promoter and
      terminator alone or combined, and expressed in E. coli BL21 (DE3) to induce
      lycopene synthesis. The results show that only T7::crtI-LeGGPS2-LePSY1 expressed
      tri-cistronically could produce lycopene, and 2.124 mg/g dry cell weight
      oflycopene was obtained when fermented for 5 h at 30 degrees C after mixing 80
      micromol/L IPTG at the later logarithmic phase while the seed broth of 1:50 (V/V)
      was inoculated into LB medium (pH 6.8) containing 3% sucrose and cultured for 8 h
      at 37 degrees C. The results confirmed the function of the prokaryonized LeGGPS2
      and LePSY1 and their synergy with crtI, and also laid a foundation to establish
      an independent lycopene synthetic pathway in the tomato plastid.

PMID- 23167195
TI  - [Hydrogen peroxide is involved in the signal transduction of salicylic acid
      induced salvianolic acid B biosynthesis in Salvia miltiorrhiza cell cultures].
AB  - Hydrogen peroxide (H2O2), one of reactive oxygen species, is widely generated in
      many biological systems, and it mediates various physiological and biochemical
      process in plants. To investigate the role of H2O2 as a signaling molecule in the
      process of salicylic acid (SA)-induced Salvianolic acid B (Sal B) accumulation,
      we separately inspected the cultured cells of Salvia miltiorrhiza with SA, H2O2,
      catalase (CAT), 2-(4-carboxy-2-phenyl)-4,4,5,5-tetramethylimidazoline-l-oxyl-3
      oxide (DMTU) and Imidazole (IMD) to investigate the influence on the activity of
      phenylalanine ammonia-lyase (PAL) and tyrosine aminotransferase (TAT) and the
      accumulation of Sal B. Treatment of S. miltiorrhiza cells with SA resulted in an
      increase of H2O2, the increase of PAL and TAT and accumulation of Sal B.
      Exogenous application of 10-30 mmol/L H2O2 was found to effectively increase PAL
      and TAT activity as well as the Sal B content. CAT, a H2O2 scavenger, eliminated
      the Sal B-accumulating effects of exogenous H2O2 and SA. These indicated that
      H2O2 may serve as an upstream signaling molecule in the SA-induced accumulation
      of Sal B signal transduction pathway. Disposed by DMTU, a chemical trap for H2O2,
      as observed to be effective in inhibiting SA-induced accumulation of Sal B. IMD
      strongly inhibits the activity of NADPH oxidase, which is one of the main sources
      of H2O2 formation in plant cells. IMD treatment strongly inhibited the
      accumulation of Sal B in cultured cells of S. miltiorrhiza, but the effects of
      IMD, can be partially reversed by the exogenous SA. The accumulation of Sal B was
      blocked once the generation of H2O2 by NADPH oxidase was inhibited, and H2O2
      served as signaling molecule mediated the SA-induced Sal B accumulation.

PMID- 23167196
TI  - [Uptake of exogenous sugars and responses by rice root of young wild-type and
      ospk1 mutant seedlings].
AB  - How root system responds to various environmental factors has not yet been fully
      elucidated. In root, the expression of OsPK1 is mainly in the maturation zone and
      the root-hair zone of root tip. It is unknown whether the uptake of exogenous
      sugars by rice seedlings is affected by downregulation of OsPK1. In this study,
      we used wild-type (WT) and ospk1 rice mutant plants to investigate the uptake of
      exogenous sugars and the responses of rice seedlings by adding sucrose to 1/2 MS
      medium or not. The contents of sucrose, glucose, fructose and galactose in leaf
      blades, sheathes and roots of rice seedlings were measured by GC-MS analysis. The
      result revealed that direct contact between root and exogenous sugars greatly
      elevates sugar levels of rice seedlings. And the root length of these seedlings
      is much longer than that of the seedlings grown in medium omitting exogenous
      sugars, suggesting that uptake of exogenous sugars by root promotes root
      elongation. Downregulation of OsPK1 has effects on sugar metabolism and the
      uptake of exogenous sugars. Semi-quantitative RT-PCR result showed that the
      expressions of OsPIP2;4, OsPIP2;5 and OsTIP2;1 (three aquaporin genes) in root
      were greatly upregulated by the direct contact between root and exogenous sugars.

PMID- 23167197
TI  - [Evaluation of isotopic labeling of lysine residues of peptides for quantitative
      proteomics].
AB  - To evaluate the reagent 2-methoxy-4,5-dihydro-1H-imidazole used for isotopic
      labeling in quantitative proteomics, we synthesized 2-methoxy-4,5-dihydro-1H
      imidazole and its tetradeuterated analog in three steps. Prior to tryptic
      cleavage, bovine serum albumin (BSA) was reduced and alkylated. Tryptic peptides
      were derivatized with an equal volume of either DO or D4 and D4-derivatized
      peptides were mixed with at variable ratio (from 10:1 to 1:5) prior to MS and
      MS/MS analysis. We used matrix assisted laser desorption/ionization-mass
      spectrometry (MALDI-MS) and Electro spray ionization-mass spectrometry (ESI-MS)
      to evaluate the quantitative capability of labeling. The specificity of the
      reagent is excellent: only lysine side chains were modified among tryptic
      peptides. MALDI and ESI ionization modes not only could achieve the
      quantification of differentially expressed proteins but also facilitate the de
      novo sequencing. This side-chain modification can be used for quantitative
      analysis with proteomic strategies involving liquid chromatography. Reverse phase
      liquid chromatography (RPLC) kept a good resolution, and the introduction of D
      atoms did not introduce a variation of retention time between heavy and light
      peptides in RPLC.

PMID- 23167198
TI  - [Enhancement of functional expression of wheat peroxidase WP1 in prokaryotic
      system by co-transforming with hemA and hemL of Esherichia coli].
AB  - Wheat grain peroxidase 1 (WP1) belonged to class III plant peroxidase with
      cofactor heme, which not only has antifungal activity, but also influences the
      processing quality of flour. In order to enhance functional expression of WP1 in
      prokaryotic system by increasing endogenous heme synthesis, we constructed a
      recombinant plasmid pACYC-A-L containing hemA and hemL of Esherichia coli. Then,
      we co-transformed it into host strain T7 Express with secretive expression vector
      (pMAL-p4x-WP1) or non-secretive expression vector (pET21a-MBP-WP1), respectively.
      The MBP-WP1 fusion protein was further purified by amylose affinity
      chromatography and its peroxidase activity was assayed using 2,2'-azino-bis (3
      ethylbenzothiazoline-6-sulfonate) (ABTS) as substrate. At 12 h after induction at
      28 degree, the extracellular 5-aminolevulinic acid (5-ALA) production of T7
      Express/pACYC-A-L was up to 146.73 mg/L, simultaneously the extracellular
      porphrins also increased dramatically. The peroxidase activity of functional MBP
      WP1 obtained from T7 Express/ (pACYC-A-L + pMAL-p4x-WP1) was 14.6-folds of that
      purified from T7 Express/ pET21a-MBP-WP1. This study not only successfully
      enhanced functional expression of wheat peroxidase 1 in Esherichia coli, but also
      provided beneficial references for other important proteins with cofactor heme.

PMID- 23167199
TI  - [Cloning, expressing of exendin-4 analogue and bioactivity analysis in vivo].
AB  - To construct, express and purify Exendin-4 analogue and detect its biological
      activity in vivo. Insert gene sequence into fusion partner ofpED plasmid which is
      helped to purification, entitled the new recombinant plasmid 5 Exendin-4 analogue
      polypeptide gene and fusion partner gene was linked by acid hydrolysisgene,
      transformed to E. coli BL21 and the fusion protein was induced by lactose. After
      acid hydrolysis, the Exendin-4 analogue polypeptide separated from fusion
      chaperon. Anion charge chromatography were used to further purification. 6 to 8
      week-old ICR mice were injected (s.c) with Exendin-4 analogue, blood glucose and
      plasma insulin level was detected in different period after oral glucose
      tolerance test. The results show that high expression of inclusion body was
      induced by lactose, which accounted for 40% of germ proteins, the Exendin-4
      analogue was obtained with the purity of 91.8% after being purified by anion
      charge chromatography. Bioactivity assay showed that the level of blood glucose
      of mouse which treated with exendin-4 analogue was obviously decreased to normal
      (P < 0.01), and the level of plasma insulin was increased obviously (P < 0.01).

PMID- 23167200
TI  - [Colloidal gold immunochromatographic strip for rapid detection of melamine].
AB  - To develop a specific, rapid, and convenient immunochromatography assay (ICA) to
      detect melamine residues in dairy products and feed sample. Colloidal gold
      particles labeled with purified monoclonal antibody against anti-melamine were
      used as the detector reagent. The MEL-OVA (the conjugate of melamine and
      ovalbumin) and goat anti-mouse melamine IgG were blotted on the test and control
      regions of nitrocellulose membrane. The strip was then assembled with sample pad,
      absorbing pad, and dorsal shield. The limit of detection (LOD) is 50 microg/L.
      The test trip was applied to detect melamine in milk, milk powder, and animal
      feeds, with detection limits of 100 microg/L for milk, 100 ng/g for milk powder,
      200 ng/g for feeds. Compared to LC-MS/MS, the ICA could be used to screen a large
      number of dairy products and feed samples for melamine residue.

PMID- 23167201
TI  - Improving patient outcomes.

PMID- 23167202
TI  - Root fracture and its management.
AB  - Root fractures are uncommon following dental trauma but are mostly diagnosed
      shortly after the injury, although occasionally at routine dental appointments.
      This paper presents the management of the different types of root fractures and
      the types of healing response suggesting the appropriate follow-up of these
      injuries. CLINICAL RELEVANCE: A thorough clinical examination supplemented with
      radiographs, vitality tests, appropriate treatment planning and subsequent follow
      up of root fractured teeth can improve the prognosis for these teeth and also
      minimize the need for subsequent extractions. Immature teeth with root fractures
      have a better chance of healing compared to teeth with fully formed roots.

PMID- 23167203
TI  - Periodontal diseases in children and adolescents: a clinician's perspective part.
AB  - Contrasting forms of periodontal disease can affect children and adolescents with
      varying prevalence, severity and extent, leading to a diverse prognosis in these
      age groups. For an early diagnosis and treatment of periodontal conditions in
      young patients, it is essential for the dental practitioner to be able to
      identify and classify the disease correctly at the earliest opportunity, applying
      basic principles along with understanding of aetiology and risk factors. The
      first part of this article discusses the classification, plaque-induced and non
      plaque-induced gingival diseases, localized and generalized forms of chronic, as
      well as aggressive, periodontitis. CLINICAL RELEVANCE: Knowledge of different
      forms of periodontal diseases affecting children and adolescents may help to
      distinguish between different forms of diseases and have value in screening and
      early diagnosis of the disease.

PMID- 23167204
TI  - The role of the general dental practitioner (GDP) in the management of abuse of
      vulnerable adults.
AB  - Abuse of vulnerable adults is largely under reported. The most common forms of
      abuse amongst this group are neglect and financial abuse, although an individual
      may be at risk of any or all forms of abuse. Certain individuals are at an
      increased risk of abuse due to their domestic environment and any physical or
      mental disability they may have. CLINICAL RELEVANCE: Vulnerable adults constitute
      a significant proportion of the population. GDPs should be aware of the signs of
      abuse, to be able to identify those individuals at risk, and how and when to
      raise concerns of abuse to social services.

PMID- 23167205
TI  - Salivary biomarkers--an update.
AB  - Saliva is the most easily available and accessible body fluid, which makes it one
      of the most sought after tools in diagnostic pathology. Markers expressed in
      saliva can be used for diagnosis and concurrent patient follow-up of diseases
      ranging from hereditary disorders to infections, as well as malignancies and also
      analysis of therapeutic levels of drugs. The emergence of hand-held devices has
      made possible the elucidation of point-of-care methods and research in the field
      has resulted in the assimilation of knowledge useful for clinical applications.
      CLINICAL RELEVANCE: This article describes some of the latest research in saliva
      diagnostics and provides some information on the various hand-held devices
      available.

PMID- 23167206
TI  - Denture fixative cream and the potential for neuropathy.
AB  - The body requires zinc in small amounts to remain healthy. Because the body
      balances zinc and copper, people who ingest excessive zinc have resulting
      dangerously low levels of copper. An acute zinc overdose itself may be toxic and
      chronic zinc ingestion results in bone marrow suppression and degeneration of the
      spinal cord, usually resulting in crippling nerve damage. It's been called'human
      swayback disease' A case of a 54-year-old female whose nerve damage greatly
      reduced her mobility due to copper deficiency myelopathy as a result of the use
      of denture fixative cream, Fixodent, is discussed. CLINICAL RELEVANCE: Many cases
      of mysterious nerve damage turn out to be caused by overuse of popular denture
      products, e.g., Fixodent. Thus we are encouraging patients to read the
      manufacturer's leaflet and follow the instructions carefully.

PMID- 23167207
TI  - A study to assess management of patients on warfarin by general dental
      practitioners (GDPs) in the West Midlands.
AB  - Current management protocols for anticoagulated patients undergoing dental
      procedures are influenced by evidence-based guidelines. These guidelines state
      that the risk of significant bleeding is low in patients who have a stable INR
      within a therapeutic range, (2-4). The risks of interruption of anticoagulant
      therapy is greater than the risk of bleeding. This paper discusses the current
      practice of general dental practitioners (GDPs) in the West Midlands when
      treating patients taking warfarin and compares these findings with standard
      guidelines. A questionnaire was sent to 638 GDPs in West Midlands in 2010, 492
      (77%) were returned. This study was carried out three years after a similar study
      carried out in South West Wales and after the guidance updated by the BNF and
      NMWIC. Thirty-three (7%) of the respondents did not treat patients on warfarin.
      The majority of respondents (86%) considered that a dental extraction in a
      patient on warfarin is a procedure associated with a high risk of bleeding.
      Surgical implant placement (75%), subgingival debridement (49%) and inferior
      dental block (40%) administration were also considered by GDPs to be associated
      with a high risk of bleeding.The majority (88%) of the respondents check the INR
      of anticoagulated patients before carrying out treatment. Of these, 244 (52%)
      would do so within 24 hours and 78 (17%) of them within 72 hours. Only 117 (25%)
      considered 4.0 as the safe upper limit for the INR for performing high-risk
      procedures. CLINICAL RELEVANCE: The findings of this study demonstrate that there
      is general awareness about how to manage patients on warfarin but uncertainties
      still exist among general dental practitioners. Further education and training
      would improve the care of patients on warfarin in a primary care setting.

PMID- 23167208
TI  - The changing face of dentistry?

PMID- 23167209
TI  - The changing face of dentistry?/Ethical marketing series.

PMID- 23167210
TI  - The changing face of dentistry?/Ethical marketing series.

PMID- 23167211
TI  - Editorial/Kelleher series.

PMID- 23167212
TI  - The changing face of dentistry?/Ethical marketing series.

PMID- 23167213
TI  - Follow the leader: part 3--Leadership pillar 2--motivation.

PMID- 23167214
TI  - Oral medicine: 2. Ulcers: serious ulcers.

PMID- 23167215
TI  - Technique tips--ADH appliance: an alternative for patients allergic to acrylic.

PMID- 23167216
TI  - Physical signs for the general dental practitioner. Case 98. Sarcoidosis.

PMID- 23167217
TI  - Factors predicting emergency surgery in severe mitral regurgitation following
      mitral balloon valvotomy.
AB  - BACKGROUND AND AIM OF THE STUDY: Acute mitral regurgitation (MR) may cause
      adverse hemodynamics following mitral balloon valvotomy (MBV). Some patients
      become severely hemodynamically unstable and require emergency mitral valve
      replacement (MVR), while others remain relatively stable with medical management.
      The study aim was to identify factors that would predict severe acute MR leading
      to severe hemodynamic compromise requiring emergency MVR. METHODS: Between
      January 2001 and July 2009, a total of 46 patients developed acute severe MR
      following MBV at the authors' institution. Of these patients, 11 developed severe
      hemodynamic compromise and required emergency MVR within 6 h of the procedure
      (group I), while 35 were relatively stable, improved with time, and were
      discharged with advice to undergo an early MVR (group II). RESULTS: The
      demographic profile and routine echocardiographic parameters were comparable
      between the two groups. In group I, the right ventricular systolic pressure
      (RVSP) before and after MBV was significantly higher, and a significantly higher
      level of calcium was present in the mitral valve leaflets. Univariate analysis of
      the RVSP before and after MBV predicted the occurrence of hemodynamic instability
      leading to emergency MVR. The receiver operating characteristic (ROC) curve for
      RVSP before and after MBV had a significant area under the curve (0.944, p <
      0.005 and 0.940, p < 0.005, respectively). Based on the ROC data, the pre- and
      post-MBV RVSPs of 76 mmHg and 77 mmHg, respectively, predicted the possibility of
      emergency MVR, with sensitivities and specificities of 72% and 63%, and 100% and
      90%, respectively. CONCLUSION: Patients undergoing MBV with an RVSP >76 mmHg and
      the presence of non-commissural calcium on the mitral valve leaflet, or those who
      develop an RVSP of 77 mmHg following the procedure will very likely require
      emergency MVR.

PMID- 23167218
TI  - Mitral annuloplasty with IMR ETlogix ring for ischemic mitral regurgitation and
      left ventricular dysfunction.
AB  - BACKGROUND AND AIM OF THE STUDY: Chronic ischemic mitral regurgitation (IMR) is
      associated with asymmetric mitral leaflet tethering and annular dilation. The
      Carpentier-McCarthy-Adams IMR ETlogix annuloplasty ring is designed specifically
      to treat these asymmetric pathological changes. In the present study, the results
      of mitral annuloplasty with this ring in a selected subset of patients with
      significant IMR and left ventricular (LV) dysfunction were analyzed. METHODS:
      Between May 2005 and September 2009, the IMR ETlogix ring was implanted in 140
      consecutive patients with grade > OR = 2+ IMR (graded from 0 to 3+). Of these
      patients, 41 (29%) suffered from preoperative LV dysfunction (defined as LV
      ejection fraction < OR = 0.35). Ten of these 41 patients underwent combined
      aortic valve replacement or LV restoration, and thus were excluded from this
      retrospective study; consequently, 31 patients (mean age 67.1 +/- 7.7 years) were
      enrolled into the study. Preoperatively, 18 patients (58%) were in NYHA class III
      or IV, and 16 (52%) were in CCS class 3 or 4. The expected operative risk
      according to the logistic EuroSCORE was 22.4 +/- 16.5%. Using two-dimensional
      echocardiography, postoperative changes in the mitral annular diameter (MAD),
      tethering area (TA), and tenting height (TH) of the mitral valve in four-chamber,
      two-chamber, and long-axis views, were assessed at mid-systole. RESULTS: All
      patients underwent complete myocardial revascularization. One (3%) in-hospital
      (non-cardiac) death occurred. During a mean follow up of 3.4 +/- 1.5 years
      (range: 0.2 to 5.9 years), one early mitral replacement was required (due to
      endocarditis), and there were two cardiac deaths and three non-cardiac deaths.
      The four-year actuarial survival and freedom from heart failure hospital
      readmission were 82% and 75%, respectively. Heart failure symptoms were improved
      (p = 0.001), and IMR was well controlled within grade 1+ (p < 0.0001) for the 24
      remaining patients. The MAD, TA and TH were each decreased in all three
      echocardiographic views (p < OR = 0.0006). The MAD reduction was greater in the
      long-axis view than in the four-chamber (56% versus 49%, p = 0.002) and two
      chamber (56% versus 43%, p = 0.0003) views. CONCLUSION: In selected patients with
      chronic ischemic LV dysfunction, mitral annuloplasty with the IMR ETlogix ring,
      combined with complete myocardial revascularization, restored the mitral
      apparatus geometry and competence.

PMID- 23167219
TI  - The impact of percutaneous coronary intervention on ischemic mitral
      regurgitation.
AB  - BACKGROUND AND AIM OF THE STUDY: The study aim was to determine if significant
      ischemic mitral regurgitation (IMR) is adequately addressed in patients
      undergoing multi-vessel percutaneous coronary intervention (PCI). METHODS: The
      cardiac catheterization laboratory database at the authors' institution was
      accessed over a five-year interval to identify those patients who had undergone
      multi-vessel PCI. Both, pre- and post-revascularization echocardiographic data
      were retrieved, and clinical data, MR presence and severity, and outcomes were
      each assessed. RESULTS: In total, 150 patients (100 males, 50 females; mean age
      63 +/- 12 years) underwent PCI. Of these 150 patients, pre-procedural
      echocardiograms were not performed in 54 cases (35%); hence, the study group
      comprised 96 patients with both pre- and postprocedural echocardiograms. Of these
      patients, 21 (22%) had moderate or greater (2+) IMR. The severity of the IMR did
      not change significantly after multivessel PCI (2 +/- 0.8+ preoperatively versus
      1.9 +/- 1.0+ postoperatively). CONCLUSION: Clinically significant IMR occurred
      not infrequently among patients treated with multivessel PCI, but the severity
      did not change with percutaneous revascularization, despite this being
      predominantly complete. In more than one-third of the patients, adequate pre-PCI
      echocardiography was unavailable, which suggested the possibility that not all
      IMR had been identified.

PMID- 23167220
TI  - Serum 25-hydroxyvitamin D levels are correlated with mitral valve calcification
      score in patients with rheumatic mitral stenosis.
AB  - BACKGROUND AND AIM OF THE STUDY: Rheumatic mitral stenosis (RMS) is a chronic
      disease related to autoimmune heart valve damage after streptococcal infection.
      Epidemiological evidence supports an association between vitamin D and the
      susceptibility and severity of autoimmune disorders. The study aim was to assess
      the serum levels of 25-hydroxyvitamin D and their correlation with Wilkins
      calcification score in patients with RMS. METHODS: Thirty-four patients with RMS
      and 29 healthy age- and gender-matched controls were enrolled in the study. All
      subjects underwent transthoracic echocardiography after a complete medical
      evaluation and laboratory examination. The planimetric mitral valve area and
      Wilkins score were evaluated for all patients, and biochemical parameters and
      serum levels of 25-hydroxyvitamin D and calcitriol were determined. RESULTS: The
      mean patient age was similar in the RMS and control groups (50 +/- 10 versus 52
      +/- 10 years; p = NS). The serum level of 25-hydroxyvitamin D was significantly
      lower in RMS patients than in controls (8.6 ng/ml; range: 4.9-26.3 ng/ml versus
      12.3 ng/ml; range: 4-158 ng/ml; p = 0.031). A significantly moderate inverse
      correlation was identified between the serum 25-hydroxyvitamin D level and the
      Wilkins score (r = -0.567, p < 0.001), but no correlation was identified between
      25-hydroxyvitamin D levels and other echocardiographic parameters of mitral
      stenosis. The serum level of calcitriol was also significantly lower in RMS
      patients than in controls (19.8 pg/ml; range: 16.0-54.6 pg/ml versus 26.1 pg/ml;
      range: 13.2-47.0 pg/ml; p = 0.013). CONCLUSION: The study results showed that
      serum levels of 25-hydroxyvitamin D were significantly lower in RMS patients than
      in controls, and also correlated with the Wilkins calcification score. Thus, a
      link may exist between 25-hydroxyvitamin D and the calcification process in RMS.

PMID- 23167221
TI  - Aortic valve replacement in asymptomatic and symptomatic patients with preserved
      left ventricular ejection fraction.
AB  - BACKGROUND AND AIM OF THE STUDY: Patients with moderate-severe aortic stenosis
      (AS) who maintain that they have no symptoms pose a decision-making dilemma. In
      order to determine whether or not preoperative symptoms were related to outcomes
      in these patients, results were compared after aortic valve replacement (AVR) in
      asymptomatic and symptomatic AS patients with a preserved left ventricular
      ejection fraction (LVEF). METHODS: Twenty asymptomatic and 18 symptomatic AS
      patients were investigated retrospectively, with clinical and echocardiographic
      studies being performed before and at 610 +/- 409 days after AVR. The patients'
      cardiopulmonary function was monitored using spiroergometry. RESULTS: Symptomatic
      AS patients improved their exercise tolerance after surgery more than
      asymptomatic patients, although exercise tolerance and LVEF remained lower in
      symptomatic patients. On comparing all postoperative objective changes between
      the groups, a difference was observed only for aortic valve area index.
      Improvements in left ventricular structure, diastolic function, and filling
      pressures after AVR were similar in both groups. Systolic function, as assessed
      by tissue Doppler, was improved only in the symptomatic group. Regression
      analyses identified preoperative exercise tolerance as the strongest independent
      determinant of postoperative functional outcome. The postoperative LVEF was
      independently predicted by the preoperative LVEF and exercise tolerance.
      CONCLUSION: Asymptomatic patients with moderate-severe AS and preserved systolic
      function exhibited similar improvements in cardiac remodeling, diastolic
      function, and filling pressures following AVR, compared to symptomatic patients.
      Differences in exercise tolerance and systolic function observed preoperatively
      between these groups were decreased after AVR.

PMID- 23167222
TI  - Reduction aortoplasty: safe and durable treatment for borderline dilatation in
      selected patients.
AB  - BACKGROUND AND AIM OF THE STUDY: In aortic valve surgery, the management of
      ascending aortic dilatation is not clearly defined. Guidelines recommend
      replacement at diameters of 50 mm, but the handling of borderline dilatation has
      not been detailed. Reduction aortoplasty has been proposed as a less invasive and
      safe option in the case of a smaller dilatation above the sinotubular junction.
      METHODS: Between 1999 and 2009, reduction aortoplasties with or without external
      reinforcement associated with aortic valve surgery were performed in 82 patients.
      The ascending aortic diameter was measured echocardiographically at a mean follow
      up (FU) of 32 months (FU was 91% complete). RESULTS: The in-hospital mortality
      was 1.2%, and all patients were in NYHA class I or II. Echocardiography revealed
      a re-dilatation (> or = 5 mm) rate of 5.5%. One patient required reoperation. At
      univariate analysis, a preoperative dilatation >45 mm, persistent postoperative
      diameters >35 mm after reduction, and a younger age at the time of surgery (<65
      years) were significant risk factors. Multivariate analysis confirmed the
      parameters for re-dilatation, and the area under the receiver operating curve was
      0.85 for these three criteria. Mesh implantation, FU duration and bicuspid valve
      had no significant impact on outcome. CONCLUSION: Reduction aortoplasty is a less
      invasive option to handle borderline supra-coronary aneurysms in the case of
      concomitant valve surgery, compared to aortic replacement. The mortality remained
      low, and equal to that for simple aortic valve replacement. A large preoperative
      aortic diameter and age < or = 65 years favored re-dilatation. Correct downsizing
      was technically demanding, but indispensable for long-term stabilization. Regard
      for these criteria could lead to numerous patients benefiting from this operative
      strategy, with good results.

PMID- 23167223
TI  - Aortic annulus diameter and valve design each determine the valve size implanted.
AB  - BACKGROUND AND AIM OF THE STUDY: The study aim was to compare the sizing
      characteristics and hemodynamics of the Medtronic Mosaic Ultra porcine and
      Carpentier-Edwards PERIMOUNT Magna bovine pericardial bioprosthetic stented
      aortic valves in relation to the patient's true aortic annulus size. METHODS: In
      this prospective multicenter randomized study, data acquired perioperatively and
      at six months postoperatively were collected. Following aortic valve excision and
      debridement, the annulus was measured by blinded sizers prior to the
      randomization of 141 patients (Ultra, n=72; Magna, n=69). RESULTS: The median
      patient age was 75 years, and 89% of the patients had aortic stenosis. A good
      left ventricular function was present in 75% of patients, and the EuroSCORE
      predicted mortality was 9%. Concomitant procedures (coronary artery bypass
      grafting, mitral/tricuspid repair, septal myectomy, modified Maze) were performed
      in 61% of patients. The in-hospital mortality was 3%, and at six months
      postoperatively 96% of the patients were NYHA class I or II, with no intergroup
      differences. The mean 'true aortic annulus' size was 23.0 +/- 1.4 mm for the
      Ultra valve, and 22.6 +/- 1.8 mm for the Magna valve (p = NS). The implanted
      labeled valve size was > or = 23 mm for 83% of Ultra valves, and for 52% of Magna
      valves (p < 0.01), and smaller than the measured true aortic diameter (44% Magna
      versus 33% Ultra). The mean echo gradients were lower with Magna valves (11 +/- 6
      mmHg) than with Ultra (17 +/- 6 mmHg; p < 0.01), while the effective orifice area
      (EOA) was higher with Magna than with Ultra (1.6 +/- 0.4 versus 1.4 +/- 0.4 ; p <
      0.01). Both groups showed a similar left ventricular mass regression (Ultra -48
      +/- 83 g; Magna -42 +/- 70 g). Trivial to moderate regurgitation was noted in 24%
      of Ultra valves compared to 48% of Magna valves (p < 0.01). CONCLUSION: Selection
      of the Ultra bioprosthetic valve allowed the implantation of larger valve sizes.
      However, when compared to the 'true aortic annulus', the Magna was associated
      with lower transprosthetic gradients and larger EOAs. The longer term
      significance of these observations remains inconclusive in terms of bioprosthesis
      selection, however.

PMID- 23167224
TI  - One-year observation of inflammatory markers in patients with aortic valve
      stenosis who expressed high or low Chlamydia pneumoniae antibody titers.
AB  - BACKGROUND AND AIM OF THE STUDY: Aortic valve stenosis (AVS) and atherosclerosis
      can be regarded as two manifestations of the same pathological process. The study
      aim was to evaluate annually the plasma levels of C-reactive protein (CRP),
      interleukin-6 (IL-6) and tumor necrosis factor alpha (TNFalpha) in AVS patients,
      and to compare these data in AVS patients with and without high IgG, IgM, and IgA
      titers against Chlamydia pneumoniae. METHODS: Sixty patients with AVS who had
      declined the offer of remedial surgery were allocated to groups according to
      their antibody titers: group A (n=30, high IgG titer), group B (n=30, low IgG
      titer), group C (n=22, high IgA titer), group D (n=38, low IgA titer), group E
      (n=7, high IgM titer), and group F (n=53, low IgM titer) Antibody titers, serum
      levels of inflammatory markers and echocardiographic scans were monitored at 12
      month intervals. RESULTS: During a one-year observation period, a greater number
      of patients in group A showed AVS deterioration compared to group B (p < 0.02).
      The mean IgA and IgM titers in group A were higher than in group B, while mean
      serum CRP and IL-6 levels, and IgG titer, tended to be higher in group C compared
      to group D. No statistically significant differences were identified in mean
      serum levels of CRP, IL-6, and TNFalpha between groups A and B. CONCLUSION: The
      results of the study suggested a possible association between C. pneumoniae
      infection and the progression of AVS.

PMID- 23167225
TI  - Abnormal left ventricular mechanics in isolated bicuspid aortic valve disease may
      be independent of aortic distensibility: 2D strain imaging study.
AB  - BACKGROUND AIM OF THE STUDY: In this study, we hypothesized that subclinical
      impairment of left ventricular (LV) mechanical function in bicuspid aortic valve
      (BAV) patients is independent of valvular hemodynamics represented by
      valvuloarterial impedance and aortic elastic characteristics. Therefore, we aimed
      to test left ventricular mechanics in cases of isolated non-stenotic BAV with non
      dilated aorta. METHODS: Thirty-three patients with isolated BAV exhibiting non
      dilated aorta, and 25 age-and gender-matched healthy subjects were included in
      the study. Patients with aortic valve velocity > 1.5 m/s and mild-to-moderate
      aortic regurgitation or ascending aorta diameter > 3.5 cm were excluded from the
      study. Aortic elasticity parameters and valvulo-arterial impedance were
      calculated. Strain measurements were reported as the peak longitudinal strain
      (LS) for four chamber (4C), long axis (LAX) and two chamber (2C) views. Strain
      rate (Sr) measurements were reported as the peak systolic strain rate (Sr-sm),
      early diastolic strain rate (Sr-em) and late diastolic strain rate (Sr-am) for
      4C, LAX and 2C views. RESULTS: Systolic and diastolic diameters of the ascending
      aorta, aortic elastic properties (aortic strain, aortic distensibility, aortic
      stiffness and aortic elastic modulus), and valvulo-arterial impedances were found
      to be comparable between the BAV and control groups. BAV group was observed to
      have statistically significantly lower 4C (18.9 +/- 1.7 vs. 17.8 +/- 1.5, p =
      0.02), LAX (19.7 +/- 1.7 vs. 17.7 +/- 1.3, p = 0.001) and 2C (20.1 +/- 1.8 vs.
      17.7 +/- 1.2, p < 0.001) peak longitudinal strain values compared with the
      control group. Moreover, LV-GS values were found to be significantly lower in the
      BAV group than in the control group (19.6 +/- 1.1 vs. 17.7 +/- 0.9, p < 0.001).
      However, there was no statistically significant difference between the groups in
      terms of Sr-sm, Sr-em ve Sr-am values in the 4C, LAX, and 2C views. CONCLUSION:
      BAV might affect LV systolic functions, assessed by 2D strain imaging, in a
      fashion independent from the valvular dynamics and aortic elasticity. This might
      show that BAV is not only a valvular disease, but possibly a ventricular disease
      as well.

PMID- 23167226
TI  - Outcomes after valve-preserving root surgery for patients with Marfan syndrome.
AB  - BACKGROUND AND AIM OF THE STUDY: In patients with Marfan syndrome (MFS), valve
      reimplantation has been proposed as superior to root remodeling. In the present
      study, both forms of valve-preserving root repair were applied and mid-term
      results analyzed in MFS patients compared to a propensity score-matched cohort.
      METHODS: Among 604 patients who underwent valve-preserving aortic root surgery
      between 1995 and 2011 at the authors' institution, 33 MFS patients (16 males, 17
      females; mean age 31 +/- 12 years) underwent either remodeling (n=21) or
      reimplantation (n=12). All patients were followed up echocardiographically, and
      the outcome with regard to late aortic valve regurgitation (AR) grade EII and
      reoperation on the aortic valve was compared between MFS patients and the matched
      cohort (n=33). RESULTS: Baseline characteristics and operative data were similar
      between the groups. Actuarial freedom from AR > or = II at seven years was 86 +/-
      8% in MFS patients and 90 +/- 10% in matched non-MFS patients (p = 0.94).
      Actuarial freedom from reoperation at seven years was 90 +/- 7% in MFS patients
      and 100% in non-MFS patients (p = 0.79). In Cox's proportional hazard's model, no
      independent risk factor, including MFS, was found for recurrent AR or
      reoperation. Within the MFS patients, remodeling and reimplantation provided an
      almost identical freedom from late AR > or = II and reoperation up to five years
      postoperatively (p = 0.55 and 0.99, respectively). CONCLUSION: The stability of
      valve-preserving aortic root repair was comparable between patients with or
      without MFS. Both forms of valve-preserving root repair can provide similar mid
      term results for MFS patients, primarily according to their root geometry.
      However, additional long-term follow up data based on a larger number of patients
      are required to confirm the evidence obtained to date.

PMID- 23167227
TI  - Effect of concomitant asymmetric septal hypertrophy when assessing the severity
      of aortic valve stenosis: an in-vitro study.
AB  - BACKGROUND AND AIM OF THE STUDY: Aortic valve stenosis (AS) is an important
      cardiovascular disease that affects between 2% and 7% of the elderly population
      in industrialized countries. AS often coexists with asymmetric septal hypertrophy
      (ASH), which is generally caused by a protrusion of the hypertrophied left
      ventricular outflow tract (LVOT) just below the aortic valve. The study aim was
      to determine, based on measurement of the aortic valve effective orifice area
      (EOA), if ASH might potentially interfere with the assessment of AS severity.
      METHODS: The effects of different levels of ASH (from normal to 90%) on the EOA
      measured from orifices mimicking different AS severities, and from a home-built
      AS model constructed from a bioprosthetic aortic valve, were examined in a
      pulsatile flow in-vitro model. RESULTS: For the most severe AS, the level of ASH
      had no impact on the measured EOA. In contrast, for the less severe AS, beyond an
      ASH level of 50% the AS severity was progressively overestimated, and reached a
      reduction of about 60% of EOA for a ASH level of 90%. CONCLUSION: The presence of
      concomitant ASH may cause an overestimation of the hemodynamic severity of AS.
      The extent of overestimation is more important in less-severe AS. Hence, the
      presence of ASH may lead the clinician to conclude, erroneously, that the AS is
      severe and that aortic valve replacement is indicated. However, beyond an ASH
      level of 50% the AS severity can be accurately determined.

PMID- 23167228
TI  - The combined effects of clinical factors and CYP2C9 and VKORC1 gene polymorphisms
      on initiating warfarin treatment in patients after cardiac valve surgery.
AB  - BACKGROUND AND AIM OF THE STUDY: Recent studies have shown that, after heart
      valve surgery, patients may require a more precise warfarin dosage than their non
      surgical counterparts. The study aim was to analyze the influence of certain
      clinical factors and CYP2C9 and VKORC1 gene polymorphisms on the efficacy of
      initiation of warfarin treatment in patients after cardiac valve surgery.
      METHODS: Following heart valve surgery, a total of 185 patients was genotyped for
      the CYP2C9*1, *2, *3 alleles and for VKORC1 (G-1639A) gene promoter polymorphism.
      RESULTS: A hierarchical stepwise multivariate linear regression model was used to
      evaluate factors affecting the optimal warfarin dosage. Patient age and body
      weight, together with hepatic malfunction in the cohort population, accounted for
      12% of the variation in warfarin dosage (R2 = 0.119). The introduction of
      concomitant medications, more than doubled (R2 = 0.316) the accuracy of the
      dosage algorithm. Medications such as cephalosporin, amiodarone, loop diuretics,
      ibuprofen or diclofenac, omeprazole and beta-blockers had significant effects on
      the warfarin daily dosage in this model. However, the greatest accuracy was
      obtained when the patient's CYP2C9 and VKORC1 genotype was introduced into the
      formula as the critical factor (R2 = 0.429). CONCLUSION: The study results
      suggested that, after cardiac valve surgery, by combining the clinical, genetic
      and anthropometric data of a patient, the warfarin dose may be estimated to 43%
      accuracy at the initiation of anticoagulant therapy.

PMID- 23167229
TI  - Management of heparin-induced thrombocytopenia during thrombolytic therapy for
      prosthetic valve thrombosis.
AB  - BACKGROUND AND AIM OF THE STUDY: Heparin-induced thrombocytopenia (HIT) is a
      serious complication of heparin administration. As HIT may occur during the
      thrombolysis of prosthetic heart valve thrombosis (PVHT) due to the
      administration of heparin, this entity should be considered during and after
      sessions of this regimen. The study aim was to investigate the development,
      diagnosis, and management of HIT during thrombolytic therapy (TT) of PHVT.
      METHODS: A diagnosis of HIT was made on a clinical basis and laboratory
      confirmation based on a particle immunofiltration assay. Serial transthoracic
      echocardiography and two-dimensional transesophageal echocardiography were used
      to detect thrombus morphology and hemodynamic changes before and after TT
      sessions in 214 patients. RESULTS: Four patients (1.9%) who underwent TT for PHVT
      were diagnosed with HIT. The mean period of onset of HIT after heparin exposure
      was 8.7 +/- 3.9 days, while mean platelet levels before and after heparin
      infusion were 308,000/mm3 and 77,250/mm3, respectively. Fondaparinux was employed
      as bridging therapy in three patients. TT resulted in a successful outcome in two
      patients, while two other patients underwent surgery for increased valve
      gradients (due to progression of obstructive PHVT during TT in one case, and
      obstructive PHVT resulting in a cerebrovascular accident in the other case).
      CONCLUSION: Details are presented of the development of HIT during TT for PHVT,
      which resulted in an increased thrombus size immediately after successful TT.
      Fondaparinux may be considered as an effective bridging treatment in this
      regimen.

PMID- 23167230
TI  - Advanced age: a contraindication for triple-valve surgery?
AB  - BACKGROUND AND AIM OF THE STUDY: With the changing age structure of the
      population, cardiothoracic surgeons must deal with an increasing number of
      patients suffering from degenerative valve disease. Septuagenarians with triple
      valve disease may be refused surgery due to a potentially high perioperative risk
      related to co-morbidities. The study aim was to elucidate the indications and
      compare outcome, with a focus on age-related mortality and morbidity. METHODS:
      Between December 1996 and July 2010, a total of 90 consecutive patients (45
      males, 45 females; mean age 68 +/- 9 years; logistic EuroSCORE 21 +/- 16%)
      underwent triple-valve surgery at Hannover Medical School. Of these patients, 70%
      had degenerative disease, 19% endocarditis, and 11% a rheumatic cause, while 24%
      underwent cardiac redo-surgery. For further analysis, the cohort was divided into
      two groups according to age: < or = 70 years (n=44) and >70 years (n=46). The
      follow up was performed according to current guidelines for reporting mortality
      and morbidity after cardiac valve interventions, including a quality of life
      assessment (Minnesota Living With Heart Failure Questionnaire; MLHFQ). RESULTS:
      Mortality among the patients was 16%, 24%, and 26% at 30, 60, and 90 days,
      respectively. The one-year survival was 69% for the whole cohort, and no
      difference was seen between the age groups. Follow up (mean 46 months) was
      complete in 96% of all patients who survived at least three months (n=67). Valve
      related morbidity was low in both groups, with predominantly a recurrence of
      tricuspid insufficiency. The MLHFQ score was similar in both groups. CONCLUSION:
      Triple-valve surgery is associated with a high perioperative risk. However, the
      acceptance of elderly patients for this surgery is not associated with a higher
      mortality or valve-related morbidity. The patients' quality of life was
      acceptable during follow up, and not affected by age. Hence, the refusal of
      surgery should depend not on old age alone but rather on an individualized
      assessment of the patient.

PMID- 23167231
TI  - Triple valve repair in children with rheumatic heart disease: long-term
      experience.
AB  - BACKGROUND AND AIM OF THE STUDY: Triple valve replacement has poor early and long
      term results, particularly in children, and few data are available on triple
      valve repair. Herein are reported the single-center, long-term results of
      combined aortic, mitral, and tricuspid valve repair in rheumatic children.
      METHODS: Ten children (mean age 12 +/- 3 years) with severe rheumatic aortic,
      mitral, and tricuspid regurgitation underwent triple valve repair over a 17-year
      period, using a tailored cusp extension to repair the aortic valve, and ring
      annuloplasty and Carpentier's techniques to repair the mitral and tricuspid
      valves. RESULTS: There were no early deaths. During a median follow up of 58
      months (range: 3 months to 16 years), no late death occurred and four patients
      (40%) required reoperation at a median of three years (range: 2.7 to 12 years).
      Reoperations included one for mitral valve replacement, one for aortic valve
      replacement, and two for aortic and mitral valve replacements. Freedom from
      reoperation was 100% at one year, 63 +/- 17% at three, five, and 10 years, and 47
      +/- 19% at 15 years. CONCLUSION: In this particularly challenging patient group,
      triple valve repair provided satisfactory initial and mid-term results, with a
      high burden of reoperation in the long term, allowing a median of three years of
      growth and subsequent placement of a larger valve at the time of actual valve
      replacement. This strategy might be considered a good palliative surgical
      approach.

PMID- 23167232
TI  - Reduction in platelet count after aortic valve replacement: comparison of three
      bioprostheses.
AB  - BACKGROUND AND AIM OF THE STUDY: Concerns have recently been raised regarding
      postoperative decreases in platelet count (PC) after aortic valve replacement
      (AVR) with the Sorin Freedom Solo (SFS) stentless bioprosthesis. In order to
      assess the relevance and the clinical impact of this phenomenon, variations in PC
      were monitored in patients with SFS valves, and compared to changes of PC in
      patients after AVR with two other bioprostheses, the Medtronic Mosaic (MOS)
      porcine valve and the Sorin Mitroflow (MIT) pericardial valve. METHODS: Three
      groups of patients (25 in each group) who had undergone AVR with a biological
      prosthesis were compared. The patients were similar in terms of their
      preoperative characteristics, including mean age, NYHA functional class, risk
      factors, EuroSCORE, and mean PC. The PC was monitored on postoperative days 1, 3,
      and 5, and again at discharge. Thrombocytopenia was considered to be 'present'
      when the PC was < 150,000/microl, and 'severe' when the PC was < 30,000/microl.
      RESULTS: No significant inter-group differences were observed in the duration of
      extracorporeal circulation or cross-clamp times. The mean postoperative PCs for
      MOS valves were 154,000 +/- 56,000/microl, 154,000 +/- 54,000/microl, 161,000 +/-
      85,000/microl, and 228,000 +/- 95,000/microl at days 1,3, and 5, and at
      discharge, respectively. For MIT valves, these values were 126,000 +/-
      37,000/microl, 113,000 +/- 38,000/microl, 130,000 +/- 46,000/microl, and 170,000
      +/- 50,000/microl, respectively. For SFS valves, the values were 99,000 +/-
      27,000/microl, 67,000 +/- 9000/microl, 78,000 +/- 54,000/microl, and 96,000 +/-
      32,000/microl, respectively. Severe thrombocytopenia was never observed in any
      patient. A significant decrease in PC occurred with SFS when compared to MOS
      valves (on days 1, 3, 5, and at discharge, p < 0.001) and to MIT valves (on days
      3, 5, and at discharge, p < 0.005). Multivariate analysis showed older age (p =
      0.001) and the SFS valve (p = 0.0002) to be incremental risk factors for
      developing severe or moderate thrombocytopenia after AVR. CONCLUSION: A reduction
      in PC occurred with all bioprostheses on postoperative day 1, while a significant
      reduction in PC was continued for SFS valves on postoperative days 3 and 5, when
      compared to MOS and MIT valves. A normalization of PC at discharge was observed
      only with MOS valves. Thrombocytopenia after AVR with biological prostheses was
      not associated with any major postoperative complication.

PMID- 23167233
TI  - Hemodynamic characteristics of Edwards Sapien aortic valve prosthesis assessed
      with transesophageal echocardiography.
AB  - BACKGROUND AND AIM OF THE STUDY: Transcatheter aortic valve implantation (TAVI)
      has become the therapy of choice in high-risk patients with aortic stenosis.
      Transesophageal echocardiography provides important anatomic and functional
      information before, during, and after any procedure. The study aim was to
      determine the hemodynamic properties of 23 and 26 mm Edwards Sapien (ES) valves
      immediately after implantation, and to compare these data to those previously
      reported for surgically implanted valves. METHODS: A total of 284 patients
      treated with transapical TAVI (90 patients with ES 23 mm valves, 194 with ES 26
      mm valves) for severe aortic stenosis was analyzed. Quantitative
      echocardiographic data were obtained both pre- and post-procedure, and stored.
      Measurements were also made of the aortic annulus diameter, and the effective
      orifice area (EOA) was also calculated. In addition, the effective energy loss
      coefficient, as a parameter of left ventricular (LV) workload assessment, was
      determined. For risk estimation of prosthesis-patient mismatch (PPM), the EOA was
      indexed by body surface area; typically, an iEOA value < 0.65 cm2/m2 was
      considered indicative of PPM. RESULTS: The LV systolic function, assessed as
      biplane ejection fraction (EF) was improved significantly (pre-procedure 53 +/-
      17% versus post-procedure 59 +/- 14%; p < 0.0001). The improvement was more
      pronounced in patients with a reduced preoperative function (correlation between
      AEF and EF pre; R = -0.55, p < 0.00001). The peak post-procedure pressure
      gradients in the 23 mm and 26 mm groups were 11.9 +/- 6.3 and 9.5 +/- 5.2 mmHg,
      respectively, the mean pressure gradient was 6.3 +/- 3.4 and 5.0 +/- 2.6 mmHg,
      and the EOA was 1.55 +/- 0.36 and 1.85 +/- 0.42 cm2. In 7.2% of all patients
      (10.1% in the 23 mm group and 5.8% in the 26 mm group; p = 0.30), the post
      procedure iEOA was below the borderline value for PPM. CONCLUSION: The main
      hemodynamic characteristics of the Edwards Sapien valves were low peak and mean
      pressure gradients, and a low incidence of PPM after TAVI. The EOA was highly
      comparable with that of stented and stentless biological prostheses used for
      conventional aortic valve surgery. An ability to maintain these favorable
      hemodynamic characteristics of the ES valves during a long-term follow up would
      serve as a strong argument to extend the indication for TAVI to lower-risk
      patients.

PMID- 23167234
TI  - Trans-apical versus surgical implantation of autologous ovine tissue-engineered
      heart valves.
AB  - BACKGROUND AND AIM OF THE STUDY: Living tissue-engineered heart valves (TEHVs)
      based on rapidly degrading scaffolds and autologous cells might overcome the
      limitations of today's valve substitutes. Following minimally invasive trans
      apical implantation into an ovine model, TEHVs showed adequate in-vivo
      functionality, but a thickening of the leaflets was observed. In order to
      evaluate the impact of the substantial tissue deformations of TEHVs associated
      with the crimping procedure during minimally invasive delivery, trans-apical and
      conventional implantation technologies were compared in an ovine model. METHODS:
      Trileaflet heart valves (n=11) based on PGA/P4HB-scaffolds, integrated into self
      expandable stents, were engineered from autologous ovine vascular-derived cells.
      After in-vitro culture, the TEHVs were either implanted surgically (n=5),
      replacing the native pulmonary valve, or delivered trans-apically (n=6) into the
      orthotopic pulmonary valve position. In-vivo functionality was assessed by
      echocardiography and by angiography for up to eight weeks. The tissue
      compositions of the explanted TEHVs and corresponding control valves were
      analyzed. RESULTS: TEHV implantations were successful in all cases. Independent
      of the implantation method, the explants demonstrated a comparable layered tissue
      formation with thickening and deposited fibrous layers. Active remodeling of
      these layers was evident in the explants, as indicated by vascularization of the
      walls, invasion of the host cells, and the formation of a luminal endothelial
      layer on the TEHV leaflets. CONCLUSION: This direct comparison of trans-apical
      and conventional surgical implantation techniques showed that crimping had no
      adverse effect on the integrity or functional outcome of TEHVs. This suggests
      that a thickening of TEHVs in vivo is neither caused by nor enhanced by the
      crimping procedure, but represents a functional tissue remodeling process.

PMID- 23167235
TI  - Favorable evolution of a 43-year-old Starr-Edwards valve in the tricuspid
      position.
AB  - The durability of a Starr-Edwards valve implanted in the tricuspid position in
      1967 to treat Ebstein's disease with tricuspid valve regurgitation. At surgery,
      cardiac permanent pacing for postoperative complete atrioventricular block was
      achieved using a nuclear-powered pacemaker (NP). Although the 43rd year of
      cardiologic follow up was free from complications, the patient--a 74-year-old
      woman--suffered symptomatic mitral regurgitation and underwent a redo mitral
      valve replacement, during which the Starr-Edwards valve and NP were left in
      place.

PMID- 23167236
TI  - Bartonella henselae endocarditis of percutaneously implanted pulmonary valve.
AB  - Percutaneous pulmonary valve implantation (PPVI) has revolutionized the
      management of right ventricular outflow tract dysfunction after repaired
      congenital heart disease. Although the technology is considered to be safe with a
      relatively low complication rate, infection is a described complication, with
      five cases of culture-positive infective endocarditis of percutaneously implanted
      pulmonary valve having been reported to date worldwide. Herein is reported the
      first ever case of culture-negative endocarditis following PPVI, caused by
      Bartonella henselae, diagnosed five years after implantation in a 15-year-old
      patient with a repaired truncus arteriosus.

PMID- 23167237
TI  - 'American correction' resembles the 'respect or resect' approach.

PMID- 23167238
TI  - A blood cyst on the anterior mitral valve leaflet complicated by cerebrovascular
      stroke.

PMID- 23167239
TI  - A case of angina from a pseudoaneurysm after aortic root replacement.

PMID- 23167240
TI  - Gaps-in-noise (GIN(c)) test results in children with and without reading
      disabilities and phonological processing deficits.
AB  - OBJECTIVE: To determine if the gaps-in-noise (GIN((c))) test could differentiate
      children with dyslexia and significant phonological awareness deficits from a
      group of children with normal reading skills. DESIGN: A prospective study of GIN
      test performance in two groups of children. Participants were administered
      routine audiological tests, a phonological processing test, and an auditory
      temporal resolution test (GIN test). Statistical testing was completed to
      determine if significant differences existed between groups on GIN test results
      and phonological processing measures, and to examine potential relationships
      between these test measures. Routine clinical analysis procedures examined the
      performance of the two groups from a clinical perspective. STUDY SAMPLE:
      Participants included 61 children between the ages of 8 years, 1 month and 9
      years, 11 months, separated into two groups: children with dyslexia and
      significant phonological deficits (Group I); normal-reading peers with age
      appropriate phonological skills (Group II). RESULTS: Children in Group I showed
      longer gap detection (GD) thresholds and lower gap identification scores than did
      the children in Group II. Results of statistical and clinical testing revealed
      significant differences between the groups. CONCLUSION: An auditory temporal
      processing deficit is a factor to be considered in children presenting with
      dyslexia and phonological processing disorders.

PMID- 23167241
TI  - Characterization of some volatile constituents of bell peppers.

PMID- 23167242
TI  - CuI/BF3.Et2O cocatalyzed aerobic dehydrogenative reactions of ketones with
      benzylamines: facile synthesis of substituted imidazoles.
AB  - A novel CuI/BF(3).Et(2)O/O(2)-mediated reaction utilizing ketones and
      benzylamines for the construction of substituted imidazoles in one step under
      mild conditions has been demonstrated. This protocol involved the removal of
      eight hydrogen atoms, the functionalization of four C(sp(3))-H bonds and three
      new C-N bond formations.

PMID- 23167243
TI  - Pharmacological evaluation of mangiferin herbosomes for antioxidant and
      hepatoprotection potential against ethanol induced hepatic damage.
AB  - CONTEXT: Fatty liver is the first stage of alcoholic damage which is reversible
      with abstinence from alcohol. Mangiferin (MF) showed potent scavenging activity
      on diphenyl-1-picrylhydrazyl radicals which stimulate liver regeneration in
      various liver injuries. OBJECTIVE: Although, MF shows hepatoprotection against
      various liver disorders but due to rapid clearance and limited solubility in
      lipoid environment, there is problem of its poor absorption from intestine hence
      poor bioavailability. Owing to which there is a need to develop MF herbosomes to
      resolve the problem of poor bioavailability to enhance the therapeutic potential.
      METHODS: Successfully prepared MF herbosomes through complexation with
      phospholipids were characterized by physicochemical, chromatography, spectroscopy
      (differential scanning calorimetry (DSC), infrared (IR), and nuclear magnetic
      resonance (NMR)), ex vivo absorption using everted small intestine sac technique
      and in vivo studies using ethanol inducing hepatotoxicity in albino rats and
      comparing the results against plain MF. RESULTS: Ex vivo study showed significant
      increased absorption of MF from prepared MF herbosomes as compared to plain MF.
      The hepatoprotective potential of MF herbosomes evaluated by in vivo study
      revealed significantly decreased levels of serum glutamate oxaloacetate
      transminase (SGOT), serum glutamate pyruvate transminase (SGPT), total bilirubin,
      and alkaline phosphatase (ALP) in MF herbosomes as compared to plain MF. MF
      herbosomes also showed significantly decreased level of malonyl dehydrogenase
      along with increased levels of reduced glutathione, superoxide dismutase (SOD)
      and catalase as compared to plain MF which was also comparable to the standard
      drug, silymarin (SL). CONCLUSION: The above mentioned results showed that
      hepatoprotective and antioxidant potency of MF enhanced due to the preparation of
      its herbosomes.

PMID- 23167244
TI  - Mechanisms of stereomutation and thermolysis of spiro-1,2-oxaphosphetanes: new
      insights into the second step of the Wittig reaction.
AB  - The experimentally observed stereomutation of spiro-1,2-oxaphosphetanes is shown
      by DFT calculations to proceed through successive M(B2) or M(B4) and M(B3)
      mechanisms involving two, four, and three Berry pseudorotations at phosphorus,
      respectively. Oxaphosphetane decomposition takes place in a single step via a
      polar transition state. The calculated activation parameters for this reaction
      are in good agreement with those determined experimentally.

PMID- 23167245
TI  - Quantum tunneling in the quadruple proton rearrangement on a hydroxyl hydrogen
      bond ring in calix[4]arene.
AB  - Proton rearrangement rates in hydrogen bond networks are dominated by classical
      activation and quantum tunneling at higher and lower temperatures, respectively.
      Calix[4]arene (C4A) has a square-ring network composed of four hydroxyl groups
      with the O...O length of ~0.265 nm. Calorimetry and dielectric relaxation
      measurements were applied to determination of the rates in the crystals of C4A
      and its deuteron analogue (C4A-d). The rearrangement rates in C4A-d exhibited
      Arrhenius dependence in the measured temperature range. On the other hand, the
      rates in C4A showed the same dependence as those in C4A-d above 200 K, deviated
      from this dependence at around 180 K, and became independent of temperature at
      around 10(-4) s(-1) below 100 K. This evidenced that the tunneling in the
      quadruple proton rearrangement proceeds at a very slow rate of 10(-4) s(-1). This
      is the first determination by calorimetry of the proton tunneling rate.

PMID- 23167246
TI  - Immunohistochemistry in the diagnosis of malignant pleural mesothelioma: trends
      in Australia and a literature review.
AB  - AIMS: The accurate diagnosis of malignant pleural mesothelioma (MPM) is essential
      for therapeutic and legal reasons. In 2006 the International Mesothelioma Panel
      advocated the use of a panel, including two mesothelial and two non-mesothelial
      immunohistochemical (IHC) markers. We assessed the changing use of IHC for the
      diagnosis of MPM in Australia over two decades in the context of current best
      practice. METHODS: Patients with a confirmed clinico-pathological diagnosis of
      MPM who underwent extrapleural pneumonectomy or pleurectomy and/or decortication
      between 1988 and 2006 were identified from the cardiothoracic database at Royal
      Prince Alfred Hospital and combined with consecutive patients reviewed by the
      Dust Diseases Board between March 2007 and March 2009. Initial diagnostic
      pathology reports were reviewed. RESULTS: A total of 289 patients were
      identified. A median of six IHC stains per sample was performed (range 0-18): two
      (range 0-5) mesothelial markers, two (0-6) carcinoma markers and two epithelial
      markers. A trend to the higher usage of antibodies in epithelioid tumors versus
      biphasic and sarcomatoid tumors was noted (P = 0.148 and 0.389, respectively).
      Testing increased from a median of three stains per sample (1988-1997) to seven
      (2006-2009). Labeling specimens with > 2 mesothelial markers and > 2 carcinoma
      markers increased to 72 and 67 percent, respectively, after 2006. CONCLUSION:
      Reflecting the acceptance of diagnostic panels and increased availability of
      antibodies, an increase in the use of IHC stains for MPM diagnosis has occurred
      over the past two decades although uncertainty persists as to the optimal panel
      composition.

PMID- 23167248
TI  - Echocardiography and cardiac magnetic resonance-based feature tracking in the
      assessment of myocardial mechanics in tetralogy of Fallot: an intermodality
      comparison.
AB  - We investigated intermodality agreements of strains from two-dimensional
      echocardiography (2DE) and cardiac magnetic resonance (CMR) feature tracking (FT)
      in the assessment of right (RV) and left ventricular (LV) mechanics in tetralogy
      of Fallot (TOF). Patients were prospectively studied with 2DE and CMR performed
      contiguously. LV and RV strains were computed separately using 2DE and CMR-FT.
      Segmental and global longitudinal strains (GLS) for the LV and RV were measured
      from four-chamber views; LV radial (global radial strain [GRS]) and
      circumferential strains (GCS) measured from short-axis views. Intermodality and
      interobserver agreements were examined. In 40 patients (20 TOF, mean age 23 years
      and 20 adult controls), LV, GCS showed narrowest intermodality limits of
      agreement (mean percentage error 9.5%), followed by GLS (16.4%). RV GLS had mean
      intermodality difference of 25.7%. GLS and GCS had acceptable interobserver
      agreement for the LV and RV with both 2DE and CMR-FT, whereas GRS had high
      interobserver and intermodality variability. In conclusion, myocardial strains
      for the RV and LV derived using currently available 2DE and CMR-FT software are
      subject to considerable intermodality variability. For both modalities, LV GCS,
      LV GLS, and RV GLS are reproducible enough to warrant further investigation of
      incremental clinical merit.

PMID- 23167247
TI  - Azurin as a protein scaffold for a low-coordinate nonheme iron site with a small
      molecule binding pocket.
AB  - The apoprotein of Pseudomonas aeruginosa azurin binds iron(II) to give a 1:1
      complex, which has been characterized by electronic absorption, Mossbauer, and
      NMR spectroscopies, as well as X-ray crystallography and quantum-chemical
      computations. Despite potential competition by water and other coordinating
      residues, iron(II) binds tightly to the low-coordinate site. The iron(II) complex
      does not react with chemical redox agents to undergo oxidation or reduction.
      Spectroscopically calibrated quantum-chemical computations show that the complex
      has high-spin iron(II) in a pseudotetrahedral coordination environment, which
      features interactions with side chains of two histidines and a cysteine as well
      as the C?O of Gly45. In the (5)A(1) ground state, the d(z(2)) orbital is doubly
      occupied. Mutation of Met121 to Ala leaves the metal site in a similar
      environment but creates a pocket for reversible binding of small anions to the
      iron(II) center. Specifically, azide forms a high-spin iron(II) complex and
      cyanide forms a low-spin iron(II) complex.

PMID- 23167249
TI  - Interleukin-2/anti-interleukin-2 monoclonal antibody immune complex suppresses
      collagen-induced arthritis in mice by fortifying interleukin-2/STAT5 signalling
      pathways.
AB  - In this study, we investigated the effects of administration of interleukin-2 (IL
      2)/JES6-1 (anti-IL-2 monoclonal antibody) immune complexes on the expansion and
      activation of regulatory T (Treg) cells, the down-regulation of T helper type 17
      (Th17) cells, and the control of the severity of collagen-induced arthritis
      (CIA). Wild-type and CIA-induced wild-type mice were injected intraperitoneally
      (i.p.) with IL-2 or IL-2/JES6-1 complex three times at 2-day intervals. Treg cell
      surface markers were analysed by flow cytometry. After injecting IL-2 or IL
      2/JES6-1, the time kinetics of IL-2 signalling molecules was examined by FACS and
      Western blotting. Concentrations of IL-17 and IL-10 were measured by ELISA.
      Injection of IL-2/JES6-1 increased the proportion of Foxp3+ Treg cells among
      splenic CD4+ T cells, which reached the highest level on day 4 after injection.
      Up-regulation of CTLA4, GITR and glycoprotein-A repetitions predominant (GARP)
      was observed. Activation of p-signal transducer and activator of transcription 5
      (STAT5) was apparent within 3 hr after injection of IL-2/JES6-1 complexes.
      Expression of IL-2 signalling molecules, including p-AKT and p-p38/mitogen
      activated protein kinase, was also higher in splenocytes treated with IL-2/JES6-1
      complexes. Injection of IL-2/JES6-1 complexes suppressed the induction of CIA and
      the production of IL-17 and inflammatory responses while increasing the level of
      IL-10 in the spleen. The expansion of Treg cells (via STAT5) and the concomitant
      increase in IL-2 signalling pathways by IL-2/JES6-1 complexes suggests their
      potential use as a novel therapeutic agent for the treatment of autoimmune
      arthritis.

PMID- 23167250
TI  - Identification of the Mycobacterium tuberculosis protein PE-PGRS62 as a novel
      effector that functions to block phagosome maturation and inhibit iNOS
      expression.
AB  - Using a genetic screen in yeast we found that Mycobacterium tuberculosis PE
      PGRS62 was capable of disrupting yeast vacuolar protein sorting, suggesting
      effects on endosomal trafficking. To study the impact of PE-PGRS62 on macrophage
      function, we infected murine macrophages with Mycobacterium smegmatis expressing
      PE-PGRS62. Infected cells displayed phagosome maturation arrest. Phagosomes
      acquired Rab5, but displayed a significant defect in Rab7 and LAMP-1 acquisition.
      Macrophages infected with M. smegmatis expressing PE-PGRS62 also expressed two-
      to threefold less iNOS protein when compared with cells infected with wild-type
      bacteria. Consistent with this, cells infected with a Mycobacterium marinum
      transposon mutant for the PE-PGRS62 orthologue showed greater iNOS protein
      expression when compared to cells infected with wild-type organisms.
      Complementation restored the ability of the mutant to inhibit iNOS expression. No
      differences in iNOS transcript levels were observed, suggesting that PE-PGRS62
      effects on iNOS expression occurred post-transcriptionally. Marked differences in
      colony morphology were also seen in M. smegmatis expressing PE-PGRS62 and in the
      M. marinum transposon mutant, suggesting that PE-PGRS62 may affect cell wall
      composition. These findings suggest that PE-PGRS62 supports virulence via
      inhibition of phagosome maturation and iNOS expression, and these phenotypes may
      be linked to effects on bacterial cell wall composition.

PMID- 23167252
TI  - Association of internal exposure of cadmium and lead with periodontal disease: a
      study of the Fourth Korean National Health and Nutrition Examination Survey.
AB  - AIMS: This study was performed to examine the association of the internal
      exposure of cadmium and lead with periodontitis in a representative sample of
      adults, who were involved in the Fourth Korea National Health and Nutrition
      Examination Survey (KNHANES). MATERIALS AND METHODS: One thousand nine hundred
      and sixty-six subjects over the age of 19 who participated in KNHANES were
      examined. Cadmium (Cd) and lead (Pb) exposure were grouped into three categories:
      low (<25th percentile), middle (25th-75th percentile) and high (>=75th
      percentile). The periodontal status was assessed by the Community Periodontal
      Index. The multivariate logistic regression analysis was performed to get the
      adjusted odds ratio (OR), and subgroup analysis was also performed. All analyses
      considered a complex sampling design. RESULTS: The multivariate logistic
      regression analysis revealed associations of Cd with periodontitis. Subjects with
      a high Cd had a 1.57 (95% CI: 1.03-2.38) times higher OR for periodontitis than
      those with a low Cd. In the subgroup analysis, the association of Pb and Cd with
      periodontitis was different according to the strata of gender and smoking.
      CONCLUSIONS: High Cd could be associated with periodontitis in females and
      current smokers, and middle Pb showed associations in females and non-smokers
      among a representative sample of adults in Korea.

PMID- 23167251
TI  - Heat shock transcriptional factors in Malus domestica: identification,
      classification and expression analysis.
AB  - BACKGROUND: Heat shock transcriptional factors (Hsfs) play a crucial role in
      plant responses to biotic and abiotic stress conditions and in plant growth and
      development. Apple (Malus domestica Borkh) is an economically important fruit
      tree whose genome has been fully sequenced. So far, no detailed characterization
      of the Hsf gene family is available for this crop plant. RESULTS: A genome-wide
      analysis was carried out in Malus domestica to identify heat shock
      transcriptional factor (Hsf) genes, named MdHsfs. Twenty five MdHsfs were
      identified and classified in three main groups (class A, B and C) according to
      the structural characteristics and to the phylogenetic comparison with
      Arabidopsis thaliana and Populus trichocarpa. Chromosomal duplications were
      analyzed and segmental duplications were shown to have occurred more frequently
      in the expansion of Hsf genes in the apple genome. Furthermore, MdHsfs
      transcripts were detected in several apple organs, and expression changes were
      observed by quantitative real-time PCR (qRT-PCR) analysis in developing flowers
      and fruits as well as in leaves, harvested from trees grown in the field and
      exposed to the naturally increased temperatures. CONCLUSIONS: The apple genome
      comprises 25 full length Hsf genes. The data obtained from this investigation
      contribute to a better understanding of the complexity of the Hsf gene family in
      apple, and provide the basis for further studies to dissect Hsf function during
      development as well as in response to environmental stimuli.

PMID- 23167253
TI  - Mayer-Rokitansky-Kuster-Hauser syndrome with type 3 von Willebrand's disease: a
      case report and review of literature.

PMID- 23167254
TI  - Fluid intake patterns: an epidemiological study among children and adolescents in
      Brazil.
AB  - BACKGROUND: Energy from liquids is one of the most important factors that could
      impact on the high prevalence of children and adolescents obesity around the
      world. There are few data on the liquid consumption in Brazil. The aim of this
      study is to evaluate the volume and quality of liquids consumed by Brazilian
      children and adolescents and to determine the proportion of their daily energy
      intake composed of liquids. METHODS: A multicenter study was conducted in five
      Brazilian cities; the study included 831 participants between 3 and 17 years of
      age. A four-day dietary record specific to fluids was completed for each
      individual, and the volume of and Kcal from liquid intake were evaluated. The
      average number of Kcal in each beverage was determined based on label
      information, and the daily energy intake data from liquids were compared with the
      recommendations of the National Health Surveillance Agency (Agencia Nacional de
      Vigilancia Sanitaria- ANVISA), the Brazilian food regulation authority, according
      to each subject's age. RESULTS: As the children aged, the volume of carbonated
      beverages that they consumed increased significantly, and their milk intake
      decreased significantly. For children between the ages of 3 and 10, milk and
      dairy products contributed the greatest daily number of Kcal from liquids. Sugar
      sweetened beverages which included carbonated beverages, nectars and artificial
      beverages, accounted for 37% and 45% of the total Kcal from liquid intake in the
      3- to 6-year-old and 7- to 10- year-old groups, respectively. Among adolescents
      (participants 11- to 17- years old), most of the energy intake from liquids came
      from carbonated beverages, which accounted for an average of 207 kcal/day in this
      group (42% of their total energy intake from liquids). Health professionals
      should be attentive to the excessive consumption of sugar sweetened beverages in
      children and adolescents. The movement toward healthier dietary patterns at the
      individual and population levels may help to improve programs for preventing
      overweight and obesity in children and adolescents. CONCLUSION: From childhood to
      adolescence the daily volume of liquid ingested increased reaching a total of 2.0
      liters on average. Of this volume, the daily volume of milk ingested decreased
      while the carbonated drinks, sweetened, nectars and artificial beverages
      increased significantly. The proportion of water remained constant in about 1/3
      of the total volume. From 3 to 17 years of age the energy intake from carbonated
      beverages increased by about 20%. The carbonated drinks on average corresponded
      to a tenth of the daily requirements of energy of adolescents.

PMID- 23167256
TI  - Eating vegetables before carbohydrates improves postprandial glucose excursions.

PMID- 23167255
TI  - Engulfment adaptor phosphotyrosine-binding-domain-containing 1 (GULP1) is a
      nucleocytoplasmic shuttling protein and is transactivationally active together
      with low-density lipoprotein receptor-related protein 1 (LRP1).
AB  - APP (amyloid precursor protein) and LRP1 (low-density lipoprotein receptor
      related protein 1) have been implicated in the pathogenesis of AD (Alzheimer's
      disease). They are functionally linked by Fe65, a PTB (phosphotyrosine-binding)
      domain-containing adaptor protein that binds to intracellular NPxY-motifs of APP
      and LRP1, thereby influencing expression levels, cellular trafficking and
      processing. Additionally, Fe65 has been reported to mediate nuclear signalling in
      combination with intracellular domains of APP and LRP1. We have previously
      identified another adaptor protein, GULP1 (engulfment adaptor PTB-domain
      containing 1). In the present study we characterize and compare nuclear
      trafficking and transactivation of GULP1 and Fe65 together with APP and LRP1 and
      report differential nuclear trafficking of adaptors when APP or LRP1 are co
      expressed. The observed effects were additionally supported by a reporter-plasmid
      based transactivation assay. The results from the present study indicate that
      Fe65 might have signalling properties together with APP and LRP1, whereas GULP1
      only mediates LRP1 transactivation.

PMID- 23167257
TI  - Quantification of the early risk of death in elderly kidney transplant
      recipients.
AB  - To inform decision making regarding transplantation in patients >= 65 years, we
      quantified the early posttransplant risk of death by determining the time to
      equal risk and equal survival between transplant recipients and wait-listed
      dialysis patients in the United States between 1995 and 2007 (total n = 25 468).
      Survival was determined using separate multivariate nonproportional hazards
      analyses in low-, intermediate- and high-risk cardiovascular risk patients.
      Compared to wait-listed patients with similar cardiovascular risk, standard
      criteria (SCD) and expanded criteria (ECD) recipients had a higher risk of death
      in the perioperative and early-posttransplant period. In contrast, low and
      intermediate risk living donor (LD) recipients had an immediate survival
      advantage compared to similar risk wait-listed patients. In all risk groups,
      transplantation was associated with a long-term survival advantage compared to
      dialysis, but there were marked differences in time to equal risk of death, and
      time to equal survival by donor type. For example, survival in high-risk
      recipients of an LD, SCD and ECD transplant became equal to that in similar risk
      wait-listed patients 130, 368 and 521 days after transplantation. Early
      posttransplant mortality risk is eliminated in low- and intermediate-risk
      patients, and markedly reduced in high-risk patients with LD transplantation.

PMID- 23167258
TI  - Authentication of male beef by multiplex fast real-time PCR.
AB  - Meat is a significant source of high-quality nutrients, which are very important
      in the diet. Among meat products, one of the most prized is bovine meat, of which
      male beef has been designated to be of a higher quality. However, because of its
      similarity with female beef, deliberate or unintentional substitutions can occur.
      To avoid this, methodology based on the fast real-time polymerase chain reaction
      has been developed to authenticate the species and gender origin of beef. This
      technique consists of two polymerase chain reactions: one bovine-specific
      reaction and another Y-chromosome-specific multiplex reaction. This methodology
      has been validated for all kinds of beef products, including those subjected to
      intensive processing treatments, and it has subsequently been applied to 10
      commercial samples labelled as ox to determine whether they are properly
      labelled. This assay has been shown to have high specificity, sensitivity and
      rapidity, with the potential to be a powerful tool in enforcing food labelling
      regulations.

PMID- 23167259
TI  - Impact of Helicobacter pylori eradication on circulating adiponectin in humans.
AB  - BACKGROUND: The relationship between Helicobacter pylori infection and metabolic
      syndrome is not well understood. Adiponectin is an adipose-derived protein
      considered to play a significant role in the development of metabolic syndrome.
      The aim of this study was to clarify the influence of H. pylori infection on
      circulating adiponectin in humans. METHODS: In a prospective study, 456 patients
      underwent endoscopy and H. pylori testing. All of the 338 H. pylori -positive
      patients received eradication therapy. Treatment was successful in 241 patients.
      Circulating adiponectin and other metabolic parameters were measured at baseline
      in all patients and 12 weeks after eradication therapy in those initially
      positive for H. pylori. RESULTS: Circulating adiponectin levels were not
      different between H. pylori -positive and H. pylori -negative patients. In the
      group with successful eradication, levels of total adiponectin and each multimer
      form were significantly increased after therapy. Conversely, the levels of total
      adiponectin and high-molecular-weight adiponectin, but not middle-molecular
      weight and low-molecular-weight adiponectin, were increased in the group with
      unsuccessful eradication after the therapy. CONCLUSIONS: Eradication therapy of
      H. pylori increased circulating adiponectin levels in Japanese individuals and
      could be beneficial for preventing metabolic syndrome conditions.

PMID- 23167260
TI  - The plasma membrane transporter SLC5A8 suppresses tumour progression through
      depletion of survivin without involving its transport function.
AB  - SLC5A8 (solute carrier gene family 5A, member 8) is a sodium-coupled transporter
      for monocarboxylates. Among its substrates are the HDAC (histone deacetylase)
      inhibitors butyrate, propionate and pyruvate. Expression of SLC5A8 is silenced in
      cancers via DNA methylation, and ectopic expression of SLC5A8 in cancer cells
      induces apoptosis in the presence of its substrates that are HDAC inhibitors. In
      the present study we show that ectopic expression of SLC5A8 in cancer cells
      translocates the anti-apoptotic protein survivin to the plasma membrane through
      protein-protein interaction resulting in depletion of nuclear survivin and also
      decreases cellular levels of survivin through inhibition of transcription. These
      SLC5A8-induced changes in the location and levels of survivin result in cell
      cycle arrest, disruption of the chromosome passenger complex involved in mitosis,
      induction of apoptosis and enhancement in chemosensitivity. These effects are
      seen independently of the transport function of SLC5A8 and histone acetylation
      status of the cell; in the presence of pyruvate, a SLC5A8 substrate and also an
      HDAC inhibitor, these effects are amplified. Ectopic expression of SLC5A8 in the
      breast cancer cell line MB231 inhibits the ability of cells to form colonies in
      vitro and to form tumours in mouse xenografts in vivo. The suppression of
      survivin transcription occurs independently of HDAC inhibition, and the
      underlying mechanism is associated with decreased phosphorylation of STAT3
      (signal transducer and activator of transcription 3). The observed effects are
      specific for survivin with no apparent changes in expression of other inhibitor
      of-apoptosis proteins. The present study unravels a novel, hitherto unrecognized,
      mechanism for the tumour-suppressive role of a plasma membrane transporter
      independent of its transport function.

PMID- 23167262
TI  - The LMA-SupremeTM as an intubation conduit in patients with known difficult
      airways: a prospective evaluation study.
AB  - BACKGROUND: Many extraglottic airway devices allow the direct passage of an adult
      sized tracheal tube, but this is not possible with the LMA-Supreme(TM) . We
      evaluated the feasibility of using the LMA-Supreme(TM)  as a conduit for
      intubation in patients with known difficult airways. METHODS: Sixty-eight adult
      patients, with preoperative predictors of difficult intubation, were scheduled
      for elective surgery under general anaesthesia. After assessing the direct
      laryngoscopy view, 23 patients with Cormack-Lehane III/IV were included in the
      study. An LMA-Supreme(TM)  was inserted, followed by the passage of a flexible
      bronchoscope loaded with an Aintree Intubation Catheter into the trachea. The
      bronchoscope and LMA-Supreme(TM)  were removed, and a tracheal tube was
      railroaded over the Aintree Intubation Catheter into the trachea. RESULTS:
      Tracheal intubation was successful in all patients using the above technique.
      SpO(2)  was >95% during the intubation procedure. CONCLUSIONS: We conclude that
      the LMA-Supreme(TM)  is a successful conduit for bronchoscopic/Aintree Intubation
      Catheter-guided intubation in patients with known difficult airway.

PMID- 23167261
TI  - C-terminal low-complexity sequence repeats of Mycobacterium smegmatis Ku modulate
      DNA binding.
AB  - Ku protein is an integral component of the NHEJ (non-homologous end-joining)
      pathway of DSB (double-strand break) repair. Both eukaryotic and prokaryotic Ku
      homologues have been characterized and shown to bind DNA ends. A unique feature
      of Mycobacterium smegmatis Ku is its basic C-terminal tail that contains several
      lysine-rich low-complexity PAKKA repeats that are absent from homologues encoded
      by obligate parasitic mycobacteria. Such PAKKA repeats are also characteristic of
      mycobacterial Hlp (histone-like protein) for which they have been shown to confer
      the ability to appose DNA ends. Unexpectedly, removal of the lysine-rich
      extension enhances DNA-binding affinity, but an interaction between DNA and the
      PAKKA repeats is indicated by the observation that only full-length Ku forms
      multiple complexes with a short stem-loop-containing DNA previously designed to
      accommodate only one Ku dimer. The C-terminal extension promotes DNA end-joining
      by T4 DNA ligase, suggesting that the PAKKA repeats also contribute to efficient
      end-joining. We suggest that low-complexity lysine-rich sequences have evolved
      repeatedly to modulate the function of unrelated DNA-binding proteins.

PMID- 23167263
TI  - Fast-drying multi-laminate bioadhesive films for transdermal and topical drug
      delivery.
AB  - No bioadhesive patch-based system is currently marketed. This is despite an
      extensive number of literature reports on such systems detailing their advantages
      over conventional pressure sensitive adhesive-based patches in wet environments
      and describing successful delivery of a diverse array of drug substances. This
      lack of proprietary bioadhesive patches is largely due to the fact that such
      systems are exclusively water-based, meaning drying is difficult. In this paper
      we describe, for the first time, a novel multiple lamination method for
      production of bioadhesive patches. In contrast to patches produced using a
      conventional casting approach, which took 48 hours to dry, bioadhesive films
      prepared using the novel multiple lamination method were dried in 15 min and were
      folded into formed patches in a further 10 min. Patches prepared by both methods
      had comparable physicochemical properties. The multiple lamination method allowed
      supersaturation of 5-aminolevulinic acid to be achieved in formed patch matrices.
      However, drug release studies were unable to show an advantage for
      supersaturation with this particular drug, due to its water high solubility. The
      multiple lamination method allowed greater than 90% of incorporated nicotine to
      remain within formed patches, in contrast to the 48% achieved for patches
      prepared using a conventional casting approach. The procedure described here
      could readily be adapted for automation by industry. Due to the reduced time,
      energy and ensuing finance now required, this could lead to bioadhesive patch
      based drug delivery systems becoming commercially viable. This would, in turn,
      mean that pathological conditions occurring in wet or moist areas of the body
      could now be routinely treated by prolonged site-specific drug delivery, as
      mediated by a commercially produced bioadhesive patch.

PMID- 23167264
TI  - Assessment of the immunotoxic potential of trichloroethylene and
      perchloroethylene in rats following inhalation exposure.
AB  - The immunotoxic potential of trichloroethylene (TCE) and perchloroethylene (PERC)
      was assessed after inhalation exposure through the evaluation of the antibody
      forming cell (AFC) response to sheep red blood cells (SRBC). Female Sprague
      Dawley rats were exposed to TCE or PERC vapor at 0, 100, 300, or 1000 ppm for 6
      h/day, 5 days/week for 4 weeks (20 exposure days). Additional 0 ppm control
      groups were included and were dosed with cyclophosphamide via intraperitoneal
      injection to serve as positive immunosuppressive controls in the SRBC assay.
      Additional end-points evaluated included liver, kidney, spleen, and thymus
      weights, hematology, cellular differentials in bronchoalveolar lavage fluid,
      histopathology of select tissues, and assessment of the phagocytic activity of
      pulmonary alveolar macrophage (PERC only). Exposure to the high concentration of
      TCE (1000 ppm) resulted in increases in relative liver and kidney weights and
      suppression of AFC responses (AFC/spleen and AFC/10(6) spleen cells) by ~ 70%,
      while no treatment-related effects were noted at 100 and 300 ppm. Animals exposed
      to PERC at levels of 300 or 1000 ppm had statistically significant increases in
      relative liver weights that were accompanied by very slight hypertrophy of the
      centrilobular hepatocytes. Animals exposed to PERC did not demonstrate a
      treatment-related effect on the AFC response and no effect was noted on the
      phagocytic activity of pulmonary alveolar macrophages. The results of these
      studies indicate that TCE had immunotoxic potential only at high exposure
      concentrations (1000 ppm), while PERC, at similar exposure concentrations, did
      not display any evidence of immunotoxicity. 

PMID- 23167265
TI  - To cut a short test even shorter: reliability and validity of a brief assessment
      of intellectual ability in schizophrenia--a control-case family study.
AB  - BACKGROUND: The potential inclusion of cognitive assessments in the DSM-V and
      large time-consuming assessments drive a need for short tests of cognitive
      impairments. We examined the reliability and validity of a brief, 15-minute,
      version of the Wechsler Adult Intelligence Scale-III (WAIS-III). METHODS: The
      sample consisted of patients diagnosed with schizophrenia (n=75), their siblings
      without schizophrenia (n=74) and unrelated healthy controls (n=84). A short WAIS
      III consists of the Digit Symbol Coding subtest, and every second (or third) item
      of Block Design, Information, and Arithmetic. Psychometric analyses were
      implemented using item-response theory (IRT) to determine the best minimal item
      short version, while maintaining the sensitivity and reliability of the IQ score.
      RESULTS: The proposed 15-minute WAIS-III gave reliable estimates of the Full
      Scale IQ (FSIQ) in all three groups in the sample. The 15-minute (select-item)
      version yielded an overall R of.95 (R(2)=.92) and IRT yielded an R of .96
      (R(2)=.92). All four subtests performed well in differentiating patients,
      relatives, and healthy controls. Multivariate analysis showed a significant
      difference in FSIQ-estimate between patients, relatives, and healthy controls,
      F(2, 202) = 19.00, p < .0001. Regression modelling showed that the three versions
      of the WAIS had similar associations with functional outcome after a 3-year
      follow-up. CONCLUSIONS: Our proposed 15-minute version of the WAIS may serve as a
      useful screening device for general intellectual ability in research or clinical
      settings, and is recommended when a quick and accurate IQ estimate is desired.

PMID- 23167266
TI  - Holmium laser enucleation of the prostate versus transurethral resection of the
      prostate: a systematic review and meta-analysis of randomized controlled trials.
AB  - OBJECTIVES: To evaluate the efficacy and safety of holmium laser enucleation of
      the prostate (HoLEP) versus transurethral resection of the prostate (TURP) for
      relief of bladder outlet obstruction (BOO) on benign prostatic hyperplasia (BPH).
      METHODS: A systematic literature search for randomized controlled trials (RCTs)
      comparing HoLEP and TURP in several databases from 1996 to 2011 were performed.
      Meta-analysis was conducted with the Review Manager Software. RESULTS: Of 248
      potential citations, 6 RCTs were included into our meta-analysis. There was no
      significant difference between the two groups in the maximum urinary flow rate
      (Qmax) and international prostate symptom score (IPSS) at 1 month (p=0.41 and
      p=0.87) or 6 months (p=0.07 and p=0.37) after treatment. However, at 12 months
      postoperatively, the Qmax and IPSS in the HoLEP group were significantly better
      than those in the TURP group (p<0.0001 and p=0.01). The results also suggested a
      benefit of HoLEP over TURP in blood loss (p=0.001), catheterization time
      (p<0.0001), hospital stay (p=0.001), and blood transfusion rate (p=0.04), while
      the results favored TURP over HoLEP for operative time (p=0.001) and the
      incidence of postoperative dysuria (p=0.003). CONCLUSIONS: Comparing with TURP,
      HoLEP showed slightly better postoperative results in Qmax and IPSS during 12
      month follow-up, as well as significantly better perioperative results and
      similarly low complication rates. However, the operative time and the incidence
      of postoperative dysuria favor TURP. Generally, HoLEP is a promising minimal
      invasive alternative to TURP for treatment of BPH.

PMID- 23167267
TI  - Ultrasonographic characterization of cervical lymphadenopathy in chronic
      autoimmune thyroiditis.

PMID- 23167268
TI  - Nitrogen-based catalysts for the electrochemical reduction of CO2 to CO.
AB  - The synthesis and application of carbon-supported, nitrogen-based organometallic
      silver catalysts for the reduction of CO(2) is studied using an electrochemical
      flow reactor. Their performance toward the selective formation of CO is similar
      to the performance achieved when using Ag as the catalyst, but comparatively at
      much lower silver loading. Faradaic efficiencies of the organometallic catalyst
      are higher than 90%, which are comparable to those of Ag. Furthermore, with the
      addition of an amine ligand to Ag/C, the partial current density for CO increases
      significantly, suggesting a possible co-catalyst mechanism. Additional
      improvements in activity and selectivity may be achieved as greater insight is
      obtained on the mechanism of CO(2) reduction and on how these complexes assemble
      on the carbon support.

PMID- 23167269
TI  - Introduction of DNACB Bits.

PMID- 23167270
TI  - Establishment of the trimester-specific reference range for free thyroxine index.
AB  - BACKGROUND: Accurate assessment of thyroid status during pregnancy is vital for
      maternal and fetal health. Because free thyroxine (FT4) values in pregnancy vary
      widely between methods, assessment of total T4 (TT4) and FT4 index (FT4I) may be
      superior to FT4 in pregnant women. However, trimester-specific reference
      intervals for FT4I have not yet been established. In this longitudinal self
      sequential survey, we aimed at determining the trimester-specific reference range
      for FT4I in healthy Iranian women with singleton pregnancies. METHODS: A total of
      466 healthy pregnant women were evaluated. After exclusion of women with history,
      ultrasonographic, or laboratory evidence of any thyroid disorder or iodine
      deficiency and those who were positive for thyroid autoantibodies, 152 women
      entered the study. Serum thyrotropin (TSH), TT4, and triiodothyronine-resine
      uptake were measured by an immunoassay method. Reference intervals were defined
      as 5th and 95th percentiles, using the bootstrap-based procedure. RESULTS: Mean
      values in the first, second, and third trimesters were 1.7+/-1.5, 1.9+/-1.8, and
      1.9+/-1.8 mIU/L for TSH; 12.9+/-3, 14.4+/-3.1, and 13.6+/-3.3 MUg/dL for TT4; and
      12.8+/-3.5, 14.2+/-3.3, and 13.5+/-3.8 for FT4I, respectively. Reference
      intervals in the first, second, and third trimesters were as follows
      (respectively): TSH-0.2-3.9, 0.5-4.1, and 0.6-4.1 mIU/L; TT4-8.2-18.5, 10.1-20.6,
      and 9-19.4 MUg/dL; and FT4I-8.5-19, 9.7-21, and 8.7-20.4. Serum TSH had no
      significant correlation with TT4. Serum TSH had a significant but weak
      correlation with FT4I only in the first trimester (r=-0.24, p=0.006). CONCLUSION:
      This study, for the first time, establishes the trimester-specific reference
      intervals for FT4I in a reference population of normal iodine-sufficient pregnant
      Iranian women.

PMID- 23167271
TI  - Structural characterization of the highly cyclized lantibiotic paenicidin A via a
      partial desulfurization/reduction strategy.
AB  - Lantibiotics are ribosomally synthesized antimicrobial peptides produced by
      bacteria that are increasingly of interest for food preservation and possible
      therapeutic uses. These peptides are extensively post-translationally modified,
      and are characterized by lanthionine and methyllanthionine thioether cross-links.
      Paenibacillus polymyxa NRRL B-30509 was found to produce polymyxins and
      tridecaptins, in addition to a novel lantibiotic termed paenicidin A. A
      bacteriocin termed SRCAM 602 previously reported to be produced by this organism
      and claimed to be responsible for inhibition of Campylobacter jejuni could not be
      detected either directly or by genomic analysis. The connectivities of the
      thioether cross-links of paenicidin A were solved using a novel partial
      desulfurization/reduction strategy in combination with tandem mass spectrometry.
      This approach overcame the limitations of NMR-based structural characterization
      that proved mostly unsuccessful for this peptide. Paenicidin A is a highly
      cyclized lantibiotic, containing six lanthionine and methyllanthionine rings,
      three of which are interlocking.

PMID- 23167272
TI  - Expedient approach to novel N-unprotected bicyclic azapyrimidine and pyridine
      structures.
AB  - A direct route to novel bicyclic N-unprotected azapyrimidine structures including
      fused five-, six-, and seven-membered rings is described involving radical
      addition and cyclization of xanthates; this approach could be partially extended
      to pyridines.

PMID- 23167273
TI  - New evidences for old concerns with oral anticoagulation in atrial fibrillation:
      focus on dabigatran.
AB  - INTRODUCTION: Nonvalvular atrial fibrillation (NVAF) is associated with a
      fivefold excess risk of stroke. Antithrombotic therapy is crucial to reduce the
      risk of stroke. During past decades, vitamin K antagonists (warfarin or
      acenocoumarol) have been widely used for this purpose. However, they have several
      disadvantages that limit their daily use in clinical practice. AREAS COVERED: In
      patients with NVAF at risk of stroke, the randomized evaluation of long-term
      anticoagulation therapy (RE-LY) trial demonstrated that, compared with warfarin,
      dabigatran 150 mg b.i.d. was associated with lower rates of stroke and systemic
      embolism but similar rates of major hemorrhage, whereas dabigatran 110 mg b.i.d.
      exhibited similar rates of stroke and systemic embolism, but lower rates of major
      hemorrhage. Fortunately, data about dabigatran are not limited to RE-LY trial. In
      fact, many substudies have been drawn, providing new and important evidences
      about the benefits of dabigatran. EXPERT OPINION: The most recent evidences about
      efficacy and safety of dabigatran in patients with NVAF, focusing on different
      substudies of RE-LY trial, are reviewed. In summary, dabigatran is beneficial not
      only in general population with NVAF but also in different subgroups of patients
      or different clinical settings (i.e., CHADS2 score, INR control, type of AF,
      elderly, previous transient ischemic attack or stroke, cardioversion and so on).

PMID- 23167274
TI  - Metformin improves endothelial function in type 1 diabetic subjects: a pilot,
      placebo-controlled randomized study.
AB  - AIMS: Several studies have investigated the effects of metformin treatment in
      patients with type 1 diabetes mellitus (T1DM). No study has hitherto examined its
      effects on endothelial function in these patients. In this study we sought to
      evaluate the effect of metformin on endothelial function in type 1 diabetic
      patients. METHODS: Forty-two uncomplicated T1DM patients were randomized in a
      placebo-controlled, double-blind, 6-month trial to treatment with either
      metformin or placebo. Glycometabolic and clinical parameters as well as flow
      mediated dilation (FMD) and nitrate-mediated dilation (NMD) of the right brachial
      artery were measured at baseline and at the end of the study. Glycaemic
      variability (GV, calculated from continuous glucose monitoring data) and a
      biomarker of oxidative stress [urinary 8-iso-prostaglandin F2alpha (PGF2alpha)]
      were also assessed. RESULTS: Baseline data were similar in the two groups.
      Compared with placebo, metformin significantly reduced body weight [-2.27 kg (95%
      confidence interval: -3.99; -0.54); p = 0.012] whilst improved FMD [1.32% (0.30;
      2.43); p = 0.013] and increased PGF2alpha [149 pg/mg creatinine (50; 248); p =
      0.004]. Notably, the improvement of FMD did not correlate with the decrease of
      body weight (r(2)  < 1%). NMD, haemoglobin A1c, GV, daily insulin dose and other
      parameters did not significantly change after the treatment comparing the two
      groups. CONCLUSIONS: Our pilot trial showed that, in uncomplicated type 1
      diabetic subjects, metformin improved FMD and increased PGF2alpha, a marker of
      oxidative stress, irrespective of its effects on glycaemic control and body
      weight. Randomized, blinded clinical trials are needed to evaluate the benefits
      and risks of metformin added to insulin in type 1 diabetes.

PMID- 23167275
TI  - Chemical analysis and biological activities of Cupressus sempervirens var.
      horizontalis essential oils.
AB  - CONTEXT: Safe and effective antioxidants are regarded as a cornerstone for the
      prevention and treatment of several types of disorders. OBJECTIVE: The present
      study aimed to investigate the antioxidant and anti-glycation properties of
      branchlet and fruit oils of Cupressus sempervirens L. var. horizontalis (Mill.)
      Gord. (Cupressaceae). MATERIALS AND METHODS: Essential oils were extracted from
      the branchlets and fruits of C. sempervirens var. horizontalis using the steam
      distillation method. A gas chromatography-mass spectrometry method was employed
      for the compositional analysis of essential oils. In order to evaluate
      antioxidant activities of oils at different concentrations (180, 220 and 260 MUg
      mL(-1)), linoleic acid peroxidation test and peroxyl radical mediated hemolysis
      of red blood cells (RBC) assay were used. Linoleic acid peroxidation was
      monitored for 4 h and determined during each hour of incubation. Antiglycation
      effects of oils at 200, 400 and 600 MUg mL(-1) were assessed using hemoglobin and
      insulin glycation assays. RESULTS: Overall, 10 volatile components were
      identified, amounting for 88.2 and 93.2% of branchlet and fruit oils,
      respectively. alpha-Pinene and delta-3-carene were major components of both
      branchlet (46.2 and 22.7%) and fruit (59.2 and 14.9%) oils. Hemoglobin glycation
      was inhibited by both branchlet (44.8, 62.6 and 54.0% at 200, 400 and 600 MUg mL(
      1), respectively) and fruit (41.0, 62.8 and 48.5%) oils. As for the insulin
      glycation, inhibitory rates were 66.1, 69.2 and 73.8% for branchlet oil, and
      80.0, 76.9 and 81.5% for fruit oil (at 200, 400 and 600 MUg mL(-1),
      respectively). RBC hemolysis was also inhibited by both branchlet (49.9, 38.5 and
      15.0% at 180, 220 and 260 MUg mL(-1), respectively) and fruit (45.9, 38.6 and
      25.0%) oil. Finally, the oils mitigated linoleic acid peroxidation which was
      peaked after 4 h for both branchlet (39.5, 35.6 and 53.4% at 180, 220 and 260 MUg
      mL(-1), respectively) and fruit (47.5, 58.6 and 59.8%) oil. CONCLUSIONS: The
      present findings suggest that essential oils obtained from the branchlets and
      fruits of C. sempervirens var. horizontalis possess antioxidant and, in
      particular, antiglycation properties. These activities may find implication in
      the prevention of diabetic and cardiovascular complications. However, further
      investigations are required to justify the traditional medical applications of
      the plant.

PMID- 23167276
TI  - Prognostic and therapeutic relevance of c-FLIP in acute myeloid leukaemia.
AB  - Chemoresistance is a major contributor to the aggressiveness of AML and is often
      due to insufficient apoptosis. The CFLAR gene is expressed as long and short
      splice forms encoding the anti-apoptotic proteins c-FLIP(L) and c-FLIP(S)
      (CFLAR(L) and CFLAR(S) , respectively) that play important roles in drug
      resistance. In univariate analyses of CFLAR mRNA expression in adult AML
      patients, those individuals with higher than median mRNA expression of the long
      splice form CFLAR(L) (but not the short splice form) had significantly lower 3
      year overall survival (P = 0.04) compared to those with low expression. In cell
      line studies, simultaneous down-regulation of c-FLIP(L) and c-FLIP(S) proteins
      using siRNA induced apoptosis in U937 and NB-4 AML cells, but not K562 or OCI
      AML3 cells. However, dual c-FLIP(L/S) downregulation sensitized all four cell
      lines to apoptosis induced by recombinant tumour necrosis factor-related
      apoptosis-inducing ligand (rTRAIL). Moreover, specific downregulation of c
      FLIP(L) was found to recapitulate the phenotypic effects of dual c-FLIP(L/S)
      downregulation. The histone deacetylase (HDAC)1/2/3/6 inhibitor Vorinostat was
      found to potently down-regulate c-FLIP(L) expression by transcriptional and post
      transcriptional mechanisms and to sensitize AML cells to rTRAIL. Further analyses
      using more selective HDAC inhibitors revealed that HDAC6 inhibition was not
      required for c-FLIP(L) down-regulation. These results suggest that c-FLIP(L) may
      have clinical relevance both as a prognostic biomarker and potential therapeutic
      target for HDAC inhibitors in AML although this requires further study.

PMID- 23167277
TI  - Short contact therapy of acne with tretinoin.
AB  - The most frequent side effect of topical retinoids is irritant contact
      dermatitis. It occurs in approximately 85% of patients; the percentage can reach
      up to 95% in patients treated with tretinoin. Severity of this dermatitis is
      moderate to severe in approximately 20% of patients. However, 15% of patients
      stop the treatment with tretinoin because of skin irritation. The authors used
      tretinoin as short contact therapy (SCT) in mild to moderate acne, in order to
      try to reduce the incidence and severity of irritant contact dermatitis. They
      present the final results of a sponsor-free, pilot, open, multicenter study.
      Seventy-four patients were treated with 0.05% tretinoin cream. It was applied
      once daily for 30 min. Treatment duration ranged from 8 to 32 weeks (mean
      duration: 12 weeks). Acne severity and treatment efficacy were evaluated by means
      of the Global Acne Grading System. A significant clinical improvement (>=50% from
      baseline) was observed in 41 patients (55.4%). Thirteen patients (17.6%)
      developed a mild skin irritation. Four patients (5.4%) stopped the treatment
      because of severe skin irritation. Efficacy of tretinoin used as SCT seems to be
      superimposable to that of tretinoin used according to standard modality.
      Tolerability of SCT with tretinoin is very good. This tolerability allows a high
      adherence of patients to the treatment and it markedly improves compliance. 

PMID- 23167278
TI  - Arabidopsis thaliana organellar DNA polymerase IB mutants exhibit reduced mtDNA
      levels with a decrease in mitochondrial area density.
AB  - Plant organelle genomes are complex and the mechanisms for their replication and
      maintenance remain unclear. Arabidopsis thaliana has two DNA polymerase genes,
      DNA polymerase IA (polIA) and polIB, that are dual targeted to mitochondria and
      chloroplasts and are differentially expressed in primary plant tissues. PolIB
      gene expression occurs at higher levels in tissues not primary for
      photosynthesis. Arabidopsis T-DNA polIB mutants have a 30% reduction in relative
      mitochondrial DNA (mtDNA) levels, but also exhibit a 70% increase in polIA gene
      expression. The polIB mutant shows an increase in mitochondrial numbers but a
      significant decrease in mitochondrial area density within the hypocotyl
      epidermis, shoot apex and root tips. Chloroplast numbers are not significantly
      different in mesophyll protoplasts. These mutants do not have a significant
      difference in total dark mitorespiration levels but exhibit a difference in light
      respiration levels and photosynthesis capacity. Organelle-encoded genes for
      components of respiration and photosynthesis are upregulated in polIB mutants.
      The mutants exhibited slow growth in conjunction with a decreased rate of cell
      expansion and other secondary phenotypic effects. Evidence suggests that early
      plastid development and DNA levels are directly affected by a polIB mutation but
      are resolved to wild-type levels over time. However, mitochondria numbers and DNA
      levels never reach wild-type levels in the polIB mutant. We propose that both
      polIA and polIB are required for mtDNA replication. The results suggest that
      polIB mutants undergo an adjustment in cell homeostasis, enabling them to
      maintain functional mitochondria at the cost of normal cell expansion and plant
      growth. 

PMID- 23167279
TI  - Spindle-cell variant of primary cutaneous follicle center lymphoma spreading to
      the hepatobiliary tree, mimicking Klatskin tumor.
AB  - Primary cutaneous follicle center lymphoma (pcFCL) is an indolent type of primary
      cutaneous B-cell lymphoma (pcBCL) rarely disseminating to other organs. PcBCL
      with spindle-cell morphology has been described as a rare variant of pcFCL but
      the prognosis data of this variant is sparse. We report a rare case of spindle
      cell pcFCL with CD20(+), CD79a(+), CD3(+), Bcl-6(+), Mum-1(-) and CD10(-) tumor
      cells that infiltrated the hepatic hilum, mimicking a Klatskin tumor. On the
      basis of the sparse published data on spindle-cell morphology of pcBCL, this
      growth pattern should elicit awareness of an increased risk of systemic
      involvement in the otherwise indolent pcFCL.

PMID- 23167280
TI  - Central role of mitochondrial injury in the pathogenesis of acute pancreatitis.
AB  - Acute pancreatitis is an inflammatory disease with no specific treatment. One of
      the main reasons behind the lack of specific therapy is that the pathogenesis of
      acute pancreatitis is poorly understood. During the development of acute
      pancreatitis, the disease-inducing factors can damage both cell types of the
      exocrine pancreas, namely the acinar and ductal cells. Because damage of either
      of the cell types can contribute to the inflammation, it is crucial to find
      common intracellular mechanisms that can be targeted by pharmacological
      therapies. Despite the many differences, recent studies revealed that the most
      common factors that induce pancreatitis cause mitochondrial damage with the
      consequent breakdown of bioenergetics, that is, ATP depletion in both cell types.
      In this review, we summarize our knowledge of mitochondrial function and damage
      within both pancreatic acinar and ductal cells. We also suggest that colloidal
      ATP delivery systems for pancreatic energy supply may be able to protect acinar
      and ductal cells from cellular damage in the early phase of the disease. An
      effective energy delivery system combined with the prevention of further
      mitochondrial damage may, for the first time, open up the possibility of
      pharmacological therapy for acute pancreatitis, leading to reduced disease
      severity and mortality.

PMID- 23167281
TI  - Pulmonary adverse events in unrelated donors of peripheral blood stem cells.

PMID- 23167282
TI  - Primary implant stability in the atrophic sinus floor of human cadaver maxillae:
      impact of residual ridge height, bone density, and implant diameter.
AB  - OBJECTIVES: Simultaneous implant placement in conjunction with lateral or
      transcrestal maxillary sinus floor augmentation gives the benefit of reduction in
      healing times and surgical interventions. Primary implant stability, however, may
      be significantly reduced in resorbed residual ridges. Aim of the present study
      was to investigate the impact of residual bone height, bone density, and implant
      diameter on primary stability of implants in the atrophic sinus floor. MATERIAL
      AND METHODS: A total of 66 NobelActive implants were inserted in the sinus floor
      of fresh human cadaver maxillae: 22 narrow (3.5 mm), 22 regular (4.3 mm), and 22
      wide (5.0 mm) diameter implants in residual ridges of 2-6 mm height. Presurgical
      computed tomographic scans were acquired to assess bone height and density.
      Primary implant stability was evaluated by insertion torque values (ITV),
      Periotest values (PTV), and Osstell implant stability quotients (ISQ). RESULTS:
      Correlations within outcomes (ITV, PTV, ISQ) were highly significant (P < 0.001).
      Radiographic bone density was found to significantly impact all three outcome
      measures (P < 0.001), while no influence of residual bone height and implant
      diameter could be revealed by multifactorial analysis. Consistent results were
      seen in all subgroups (including residual ridges of 5-6 mm height). CONCLUSIONS:
      Bone density seems to represent the major determinant of primary stability in
      maxillary sinus augmentation with simultaneous implant placement (as well as 5-6
      mm short implants in the maxillary sinus floor). Preoperative bone density
      assessment may help to avoid stability-related complications in one-stage implant
      treatment of the atrophic posterior maxilla.

PMID- 23167283
TI  - Intensive buffering can keep pH above 7.2 for over 4 h during apnea: an
      experimental porcine study.
AB  - BACKGROUND: Ventilation with low tidal volumes reduces mortality in acute
      respiratory distress syndrome. A further reduction of tidal volumes might be
      beneficial, and it is known that apneic oxygenation (no tidal volumes) with
      arteriovenous CO(2)  removal can keep acid-base balance and oxygenation normal
      for at least 7 h in an acute lung injury model. We hypothesized that adequate
      buffering might be another approach and tested whether tris-hydroxymethyl
      aminomethane (THAM) alone could keep pH at a physiological level during apneic
      oxygenation for 4 h. METHODS: Six pigs were anesthetized, muscle relaxed, and
      normoventilated. The lungs were recruited, and apneic oxygenation as well as
      administration of THAM, 20 mmol/kg/h, was initiated. The experiment ended after
      270 min, except one that was studied for 6 h. RESULTS: Two animals died before
      the end of the experiment. Arterial pH and arterial carbon dioxide tension
      (PaCO(2) ) changed from 7.5 (7.5, 7.5) to 7.3 (7.2, 7.3) kPa, P < 0.001 at 270
      min, and from 4.5 (4.3, 4.7) to 25 (22, 28) kPa, P < 0.001, respectively. Base
      excess increased from 5 (3, 6) to 54 (51, 57) mM, P < 0.001. Cardiac output and
      arterial pressure were well maintained. The pig, which was studied for 6 h, had
      pH 7.27 and PaCO(2)  27 kPa at that time. CONCLUSION: With intensive buffering
      using THAM, pH can be kept in a physiologically acceptable range for 4 h during
      apnea.

PMID- 23167284
TI  - Comparison between pulsed ultrasound and low level laser therapy on experimental
      haemarthrosis.
AB  - The use of pulsed ultrasound (PUS) and low level laser therapy (LLLT) in patients
      with haemophilia has been recommended for supportive treatment of acute and
      chronic phases of haemarthrosis but its role has not been supported by
      experimental evidence. The purpose of the present study was to evaluate the
      effect of these modalities on joint swelling, friction and biomechanical
      parameters of articular cartilage. An experimental rabbit knee haemarthrosis
      model was used to test the hypothesis that LLLT and PUS favourably impacted on
      the biotribological and biomechanical properties of cartilage after joint
      bleeding. To test this, 35 male albino rabbits weighing 1.5-2 kg were used. The
      left knee of 30 rabbits was injected with 1 mL of fresh autologous blood two
      times per week for four consecutive weeks to simulate recurrent haemarthrosis;
      five rabbits served as non-bleeding controls. Ten rabbits were treated with PUS
      and 10 with LLLT and the remaining 10 were not treated. The treatments were
      started after 2 days and the treatment duration was planned for 5 days (sessions)
      in ultrasound and laser groups. A low level Ga-Al-As laser was applied with an
      810 nm wavelength, 25 mW power, and 1 J cm(-2) dosage for 200 s duration. The PUS
      treatment was applied with a duty cycle of 1/9, frequency of 1 MHz, and power of
      0.4 W cm(-2) for 150 s. Joint perimeter was measured before the procedure at the
      beginning of therapies and after cessation of the procedure. Friction and
      biomechanical parameters were measured immediately after the killing of the
      animals. The results demonstrate that PUS was more effective in reducing knee
      joint swelling than LLLT. Moreover, PUS had the unique ability of reducing the
      joint friction below normal values. However, it was not successful in returning
      the articular cartilage force and stiffness to normal state. LLLT was more
      effective in increasing equilibrium force of the articular cartilage than PUS,
      however, neither therapy normalized this parameter. From these data, we conclude
      that PUS is more effective than LLLT in reducing joint swelling and articular
      joint friction after experimental haemarthrosis.

PMID- 23167285
TI  - Impact of diabetes mellitus onset on sickness absence from work--a 15-year follow
      up of the GAZEL Occupational Cohort Study.
AB  - AIMS: Previous studies do not provide an accurate estimate of the burden of
      diabetes on sickness absence. The aim of this study was to measure the impact of
      diabetes onset on absenteeism starting from the earliest occurrence of the
      disease. METHODS: The authors used data from a subsample of the French GAZEL
      cohort of 506 employees with incident diabetes and 2530 matched diabetes-free
      participants. Medically certified sickness absence data were obtained from
      company records (1989-2007). Number of sickness absence days and incidence rates
      of overall and cause-specific absence spells were compared according to diabetes
      status across three 5-year periods ranging from 10 years before to 5 years after
      onset of cases' diabetes. RESULTS: The mean number of sickness absence days was
      persistently higher in participants with diabetes compared with those without
      diabetes. This difference increased from 16.4 days (95% confidence interval 7.2
      25.5) during the 5-year period preceding diabetes onset to 28.5 days (95% CI 16.1
      40.9) during the following 5-year period (P = 0.04). This was due to a steeper
      relative increase in the incidence of long (but not short) absence spells in
      participants with diabetes versus those without diabetes [incidence rate ratios
      1.33 (95% CI 1.08-1.64) and 1.75 (95% CI 1.43-2.14), respectively; P = 0.02].
      Diabetes onset was associated with increased rates of circulatory and metabolic
      absence spells. CONCLUSIONS: Onset of diabetes is associated with a substantial
      increase in sickness absence. This suggests that in addition to its burden on
      work cessation, diabetes weighs heavily on working ability among people who
      manage to remain employed.

PMID- 23167287
TI  - Models for identification of erroneous atom-to-atom mapping of reactions
      performed by automated algorithms.
AB  - Machine learning (SVM and JRip rule learner) methods have been used in
      conjunction with the Condensed Graph of Reaction (CGR) approach to identify
      errors in the atom-to-atom mapping of chemical reactions produced by an automated
      mapping tool by ChemAxon. The modeling has been performed on the three first
      enzymatic classes of metabolic reactions from the KEGG database. Each reaction
      has been converted into a CGR representing a pseudomolecule with conventional
      (single, double, aromatic, etc.) bonds and dynamic bonds characterizing chemical
      transformations. The ChemAxon tool was used to automatically detect the matching
      atom pairs in reagents and products. These automated mappings were analyzed by
      the human expert and classified as "correct" or "wrong". ISIDA fragment
      descriptors generated for CGRs for both correct and wrong mappings were used as
      attributes in machine learning. The learned models have been validated in n-fold
      cross-validation on the training set followed by a challenge to detect correct
      and wrong mappings within an external test set of reactions, never used for
      learning. Results show that both SVM and JRip models detect most of the wrongly
      mapped reactions. We believe that this approach could be used to identify
      erroneous atom-to-atom mapping performed by any automated algorithm.

PMID- 23167286
TI  - Current iodine nutrition status and progress toward elimination of iodine
      deficiency disorders in Jazan, Saudi Arabia.
AB  - BACKGROUND: The term iodine deficiency disorders (IDD) refers to all the effects
      of iodine deficiency on growth and development in human and animal populations
      that can be prevented by correction of the iodine deficiency. The objective of
      this paper was to determine the iodine nutrition status among schoolchildren in
      the Jazan Region of the Kingdom of Saudi Arabia (KSA), by measuring urinary
      iodine concentrations and by clinical assessments of goiter rate. METHODS: A
      school-based cross-sectional survey was conducted in the Jazan region of
      southwestern KSA from May to November 2010. A total of 311 children, aged 6-13
      years, drawn from 12 schools, were selected by a three-stage cluster random
      sampling method. Data on sociodemographic characteristics were collected using a
      structured questionnaire. Urine samples were collected and physical examinations
      were conducted to determine the presence or absence of goiter. Data were analyzed
      using SPSS version 17.0. Chi square and independent t-tests were used for
      proportions and mean comparisons between groups. RESULTS: Out of 360 selected
      children, 311 were examined. There were 131 males (42%) and 180 females (58%).
      The median urinary iodine concentration (UIC) of the study group was 421 MUg/L.
      The study population proportion with UIC > 300 MUg/L was 74% with a higher
      proportion among males and urban populations. The proportion of children with UIC
      of 100-300 MUg/L was only 21% and was significantly higher among females compared
      with males (p < 0.001). Only about 3% of the children had a median UIC less than
      50 MUg/L. The prevalence of total goiter rate (TGR) among the sample of
      schoolchildren in Jazan was 11%, with significant variations between rural and
      urban populations and by gender. CONCLUSIONS: The present study demonstrates a
      remarkable achievement in Universal Salt Iodization (USI) and IDD elimination
      goals in the Jazan area. However, UIC levels reflect excessive iodine intake and
      may put the population at risk of adverse health consequences like iodine-induced
      hyperthyroidism and autoimmune thyroid diseases.

PMID- 23167288
TI  - Absorption characteristics of epidural levobupivacaine with adrenaline and
      clonidine in children.
AB  - AIM: To determine if the addition of adrenaline, clonidine, or their combination
      altered the pharmacokinetic profile of levobupivacaine administered via the
      caudal epidural route in children. METHODS: Children aged <18 years old scheduled
      to undergo sub-umbilical surgery were administered caudal levobupivacaine plain
      2.5 mg . ml(-1) or with adjuvants adrenaline 5 mcg . ml(-1) or clonidine 2 mcg .
      ml(-1) or their combination. Covariate analysis included weight and postnatal age
      (PNA). Time-concentration profile analysis was undertaken using nonlinear mixed
      effects models. A one-compartment linear disposition model with first-order input
      and first-order elimination was used to describe the data. The effect of either
      clonidine or adrenaline on absorption was investigated using a scaling parameter
      (Fabs(CLON), Fabs(ADR)) applied to the absorption half-life (Tabs). RESULTS:
      There were 240 children (median weight 11.0, range 1.9-56.1 kg; median postnatal
      age 16.7, range 0.6-167.6 months). Absorption of levobupivacaine was faster when
      mixed with clonidine (Fabs(CLON) 0.60; 95%CI 0.44, 0.83) but slower when mixed
      with adrenaline (Fabs(ADR) 2.12; 95%CI 1.45, 3.08). The addition of adrenaline to
      levobupivacaine resulted in a bifid absorption pattern. While initial absorption
      was unchanged (Tabs 0.15 h 95%CI 0.12, 0.18 h), there was a late absorption peak
      characterized by a Tabs(LATE) 2.34 h (95%CI 1.44, 4.97 h). The additional use of
      clonidine with adrenaline had minimal effect on the bifid absorption profile
      observed with adrenaline alone. Neither clonidine nor adrenaline had any effect
      on clearance. The population parameter estimate for volume of distribution was
      157 l 70 kg(-1). Clearance was 6.5 l . h(-1) 70 kg(-1) at 1-month PNA and
      increased with a maturation half-time of 1.6 months to reach 90% of the mature
      value (18.5 l . h(-1) 70 kg(-1)) by 5 months PNA. CONCLUSIONS: The addition of
      adrenaline decreases the rate of levobupivacaine systemic absorption, reducing
      peak concentration by half. Levobupivacaine concentrations with adrenaline
      adjuvant were reduced compared to plain levobupivacaine for up to 3.5 hours.
      Clonidine as an adjuvant results in faster systemic absorption of levobupivacaine
      and similar concentration time profile to levobupivacaine alone. Adding
      adrenaline with clonidine does not alter the concentration profile observed with
      adrenaline alone.

PMID- 23167289
TI  - Generation and analysis of expressed sequence tags in the extreme large genomes
      Lilium and Tulipa.
AB  - BACKGROUND: Bulbous flowers such as lily and tulip (Liliaceae family) are monocot
      perennial herbs that are economically very important ornamental plants worldwide.
      However, there are hardly any genetic studies performed and genomic resources are
      lacking. To build genomic resources and develop tools to speed up the breeding in
      both crops, next generation sequencing was implemented. We sequenced and
      assembled transcriptomes of four lily and five tulip genotypes using 454 pyro
      sequencing technology. RESULTS: Successfully, we developed the first set of
      81,791 contigs with an average length of 514 bp for tulip, and enriched the very
      limited number of 3,329 available ESTs (Expressed Sequence Tags) for lily with
      52,172 contigs with an average length of 555 bp. The contigs together with
      singletons covered on average 37% of lily and 39% of tulip estimated
      transcriptome. Mining lily and tulip sequence data for SSRs (Simple Sequence
      Repeats) showed that di-nucleotide repeats were twice more abundant in UTRs
      (UnTranslated Regions) compared to coding regions, while tri-nucleotide repeats
      were equally spread over coding and UTR regions. Two sets of single nucleotide
      polymorphism (SNP) markers suitable for high throughput genotyping were
      developed. In the first set, no SNPs flanking the target SNP (50 bp on either
      side) were allowed. In the second set, one SNP in the flanking regions was
      allowed, which resulted in a 2 to 3 fold increase in SNP marker numbers compared
      with the first set. Orthologous groups between the two flower bulbs: lily and
      tulip (12,017 groups) and among the three monocot species: lily, tulip, and rice
      (6,900 groups) were determined using OrthoMCL. Orthologous groups were screened
      for common SNP markers and EST-SSRs to study synteny between lily and tulip,
      which resulted in 113 common SNP markers and 292 common EST-SSR. Lily and tulip
      contigs generated were annotated and described according to Gene Ontology
      terminology. CONCLUSIONS: Two transcriptome sets were built that are valuable
      resources for marker development, comparative genomic studies and candidate gene
      approaches. Next generation sequencing of leaf transcriptome is very effective;
      however, deeper sequencing and using more tissues and stages is advisable for
      extended comparative studies.

PMID- 23167290
TI  - Intramyocardial dissecting hematoma and postinfarction cardiac rupture.
AB  - Potentially fatal cardiac rupture is a complication of myocardial infarction
      (MI), which can appear in the first hours of the acute event and during the
      course of the first week. The intramyocardial dissecting hematoma might appear as
      a component of the rupture during the evolution process. The description of the
      myocardium as a helical muscular band facilitates the explanation of the fiber
      dissection. With echocardiography, it is possible to diagnose intramyocardial
      dissecting hematomas (IDH), determine its location, progression, potential
      complications, and in some cases its reabsorption. It is necessary to search for
      neocavitations in the infarcted myocardium and identify the intramyocardial edge
      that surrounds the defect, as well as the flow inside the myocardial dissection,
      the pathway of the dissection, and its communication with ventricular cavities,
      and also to look for the complete or partial reabsorption of the cavitary image.
      The greater the myocardial dissection is, the worse the prognosis. If the
      dissecting hematoma is confined to the apical segments, it is more likely to
      reabsorb spontaneously. Tissue characterization with magnetic resonance during an
      acute myocardial infarction allows identification of reperfusion injuries with
      altered microcirculation and intramyocardial hemorrhage (IMH). It is necessary to
      search for IMH in reperfused patients with ventricular arrhythmias, stunned
      myocardium, and no reflow. These patients may develop an increased stiffness in
      the infarcted wall and a major likelihood to develop a parietal rupture.
      Everything seems to indicate that we are facing the same physiopathological
      process which can be characterized by 2 complementary imaging methods,
      echocardiography and magnetic resonance.

PMID- 23167291
TI  - 5-aza-2'-deoxycytidine has minor effects on differentiation in human thyroid
      cancer cell lines, but modulates genes that are involved in adaptation in vitro.
AB  - BACKGROUND: In thyroid cancer, the lack of response to specific treatment, for
      example, radioactive iodine, can be caused by a loss of differentiation
      characteristics of tumor cells. It is hypothesized that this loss is due to
      epigenetic modifications. Therefore, drugs releasing epigenetic repression have
      been proposed to reverse this silencing. METHODS: We investigated which genes
      were reinduced in dedifferentiated human thyroid cancer cell lines when treated
      with the demethylating agent 5-aza-2'-deoxycytidine (5-AzadC) and the histone
      deacetylase inhibitors trichostatin A (TSA) and suberoylanilide hydroxamic acid,
      by using reverse transcriptase-polymerase chain reaction and microarrays. These
      results were compared to the expression patterns in in vitro human differentiated
      thyrocytes and in in vivo dedifferentiated thyroid cancers. In addition, the
      effects of 5-AzadC on DNA quantities and cell viability were investigated.
      RESULTS: Among the canonical thyroid differentiation markers, most were not, or
      only to a minor extent, re-expressed by 5-AzadC, whether or not combined with TSA
      or forskolin, an inducer of differentiation in normal thyrocytes. Furthermore, 5
      AzadC-modulated overall mRNA expression profiles showed only few commonly
      regulated genes compared to differentiated cultured primary thyrocytes. In
      addition, most of the commonly strongly 5-AzadC-induced genes in cell lines were
      either not regulated or upregulated in anaplastic thyroid carcinomas. Further
      analysis of which genes were induced by 5-AzadC showed that they were involved in
      pathways such as apoptosis, antigen presentation, defense response, and cell
      migration. A number of these genes had similar expression responses in 5-AzadC
      treated nonthyroid cell lines. CONCLUSIONS: Our results suggest that 5-AzadC is
      not a strong inducer of differentiation in thyroid cancer cell lines. Under the
      studied conditions and with the model used, 5-AzadC treatment does not appear to
      be a potential redifferentiation treatment for dedifferentiated thyroid cancer.
      However, this may reflect primarily the inadequacy of the model rather than that
      of the treatment. Moreover, the observation that 5-AzadC negatively affected cell
      viability in cell lines could still suggest a therapeutic opportunity. Some of
      the genes that were modulated by 5-AzadC were also induced in nonthyroid cancer
      cell lines, which might be explained by an epigenetic modification resulting in
      the adaptation of the cell lines to their culture conditions.

PMID- 23167292
TI  - Long-term functional outcome of patients with longitudinal radial deficiency:
      cross-sectional evaluation of function, activity and participation.
AB  - PURPOSE: To evaluate all functional aspects of patients with longitudinal radial
      dysplasia and to clarify the relationship between body functions on the one hand
      and limitations in activity and participation on the other hand. METHODS: Thirty
      one arms of seventeen adult patients with longitudinal radial dysplasia were
      analysed. Body function was assessed by measuring grip and pinch strength and
      active range of motion (ROM) of the hand. Activities were measured using the
      "Sequential Occupational Dexterity Assessment ", to measure perceived
      restrictions in participation the "Impact on Participation and Autonomy
      questionnaire" was used. Relationships between severity of dysplasia, body
      function, participation and activity were determined. RESULTS: Patients with a
      severe type scored significantly lower in body function scores than patients with
      a mild form. Patients with limited active finger joint motion performed worse on
      activities. We found no significant differences in activity and participation
      between mild or severe types and found no correlation in participation scores.
      CONCLUSION: Although considerable restrictions in joint mobility and strength
      were revealed, little or no limitations on the activity and participation level
      were found. Limitations in body functions hardly influenced capacity on activity
      level and did not influence participation in societal roles.

PMID- 23167293
TI  - Au40(SR)24 cluster as a chiral dimer of 8-electron superatoms: structure and
      optical properties.
AB  - We predict and analyze density-functional theory (DFT)-based structures for the
      recently isolated Au(40)(SR)(24) cluster. Combining structural information
      extracted from ligand-exchange reactions, circular dichroism and transmission
      electron microscopy leads us to propose two families of low-energy structures
      that have a chiral Au-S framework on the surface. These families have a common
      geometrical motif where a nonchiral Au(26) bi-icosahedral cluster core is
      protected by 6 RS-Au-SR and 4 RS-Au-SR-Au-SR oligomeric units, analogously to the
      "Divide and Protect" motif of known clusters Au(25)(SR)(18)(-/0), Au(38)(SR)(24)
      and Au(102)(SR)(44). The strongly prolate shape of the proposed Au(26) core is
      supported by transmission electron microscopy. Density-of-state-analysis shows
      that the electronic structure of Au(40)(SR)(24) can be interpreted in terms of a
      dimer of two 8-electron superatoms, where the 8 shell electrons are localized at
      the two icosahedral halves of the metal core. The calculated optical and
      chiroptical characteristics of the optimal chiral structure are in a fair
      agreement with the reported data for Au(40)(SR)(24).

PMID- 23167294
TI  - Proteomics and in silico approaches to extend understanding of the glutathione
      transferase superfamily of the tropical liver fluke Fasciola gigantica.
AB  - Fasciolosis is an important foodborne, zoonotic disease of livestock and humans,
      with global annual health and economic losses estimated at several billion US$.
      Fasciola hepatica is the major species in temperate regions, while F. gigantica
      dominates in the tropics. In the absence of commercially available vaccines to
      control fasciolosis, increasing reports of resistance to current chemotherapeutic
      strategies and the spread of fasciolosis into new areas, new functional genomics
      approaches are being used to identify potential new drug targets and vaccine
      candidates. The glutathione transferase (GST) superfamily is both a candidate
      drug and vaccine target. This study reports the identification of a putatively
      novel Sigma class GST, present in a water-soluble cytosol extract from the
      tropical liver fluke F. gigantica. The GST was cloned and expressed as an
      enzymically active recombinant protein. This GST shares a greater identity with
      the human schistosomiasis GST vaccine currently at Phase II clinical trials than
      previously discovered F. gigantica GSTs, stimulating interest in its immuno
      protective properties. In addition, in silico analysis of the GST superfamily of
      both F. gigantica and F. hepatica has revealed an additional Mu class GST, Omega
      class GSTs, and for the first time, a Zeta class member.

PMID- 23167295
TI  - Total synthesis of natural p-quinol cochinchinenone.
AB  - Cochinchinenone has been synthesized in only five steps and four pots and in 58%
      overall yield from commercially available 2,3-dimethoxy-4-hydroxy-benzaldehyde
      and OPMB-protected p-hydroxy acetophenone, the key step being the oxone-mediated
      oxidative dearomatization of the corresponding ketone-containing p-substituted
      phenol.

PMID- 23167296
TI  - Safety of no bowel preparation before ileal urinary diversion.
AB  - Study Type - Harm (case series) Level of Evidence 4. What's known on the subject?
      and What does the study add? Recent studies show no advantage of bowel
      preparation before ileal urinary diversion and that avoidance of bowel
      preparation led to early restoration of intestinal function and shorter hospital
      stay. However, this was not tested in a prospective comparison. The current study
      is a prospective comparison to test for the safety of omitting bowel preparation
      before ileal urinary diversion. This study also examines simultaneous effects of
      bowel preparation on the ileal flora and mucosa. OBJECTIVE: * To evaluate the
      safety of no bowel preparation before ileal reconstructive procedures of the
      lower urinary tract, in comparison to standard 3-day bowel preparation. The
      present study also examines the effects of bowel preparation on small bowel wall
      and bacterial flora. PATIENTS AND METHODS: * This study enrolled 40 patients
      scheduled for radical cystectomy and ileal urinary diversion, presenting to the
      department of urology, Alexandria University, Alexandria, Egypt during the period
      from January 2009 to September 2010. * Patients were prospectively randomized
      into two groups: Group (I) had standard 3-day bowel preparation. Group (II) had
      only over-night fasting before surgery. * Intra-operatively, one ml of ileal
      fluid was collected for bacteriological studies and an ileal wall biopsy was
      taken for histopathological examination. * Postoperative complications were
      reported for all patients using modified Clavien system. RESULTS: * Both groups
      showed insignificant difference regarding the frequency and Clavien grade of
      postoperative complications (P = 0.30). * Under aerobic and anaerobic conditions,
      5 cases in group (I) had bacterial overgrowth of E. coli (>105) versus none in
      group (II) (P = 0.04). Eight patients in group (I) had sterile ileal fluid
      cultures versus 18 patients (90%) in group (II). No correlation could be made
      between would infections and the organisms isolated in ileal fluid cultures. *
      Histopathological examination of ileal biopsies revealed mucosal edema and
      submucosal congestion in 9 cases in group (I) versus 2 cases in group (II) (P =
      0.0310). CONCLUSIONS: * Omitting bowel preparation before ileal urinary diversion
      is safe, with no added complications. * Non-preparation of the small bowel is not
      associated with bacterial overgrowth.

PMID- 23167297
TI  - The cam-path forward.

PMID- 23167298
TI  - Molecular elements of low-oxygen signaling in plants.
AB  - Oxygen and its limitation are emerging as a crucial factor in plant fitness,
      growth and development. Recent studies revealed the mechanisms by which oxygen is
      perceived by plant cells. This sensory system partly relies on an oxygen-mediated
      branch of the N-end rule pathway for protein degradation acting on a specific
      clade of ethylene responsive transcription factors (ERF-VII). A complementary
      regulative step is provided by aerobic sequestration of an ERF-VII protein at the
      plasma membrane and its timely release when hypoxia occurs. Complete absence of
      oxygen triggers the transient accumulation of reactive hydrogen peroxide and
      induces an additional set of reactive oxygen species-related genes involved in
      both signaling and attenuation of oxidative stress. Moreover, temporary hypoxic
      environments that are built up as consequence of dense cell packing have been
      demonstrated to trigger cell-fate determination in maize anthers. Similarly,
      limited oxygen delivery in bulky fruit or tuber tissues growing in aerobic
      conditions were shown to stimulate anaerobic-like responses. These advances in
      low-oxygen signaling and its effect on cell development highlight the importance
      of taking hypoxia into account in agronomical practices as well as in breeding
      programs.

PMID- 23167299
TI  - Cutaneous metastasis as the presenting sign of papillary thyroid carcinoma.
AB  - Cutaneous metastasis of visceral tumors accounts for 2% of skin tumors. We report
      the case of a 71-year-old male with a smoking history who presented to
      dermatology department with a violaceous nodule of the right sideburn skin. The
      lesion was interpreted as an adenocarcinoma that was completely excised and was
      suspicious for a metastasis. There was a recommendation for additional work-up.
      At a different institution, a positron emission tomography scan showed a left
      hilar mass and uptake in the right thyroid. He was then referred to our hospital
      for tissue diagnosis. Mediastinoscopy with biopsy of the left hilar mass showed
      metastatic follicular thyroid carcinoma. Subsequently, a thyroid fine needle
      aspirate showed suspicion for malignancy with similar morphology. Thyroidectomy
      and central neck dissection showed right thyroid papillary carcinoma extending to
      one margin and involving the lymph nodes. The left hilar metastasis mass
      resection showed similar lymph node findings. A re-review of the sideburn
      excision revealed similar histopathology to the thyroid and mediastinal
      resection. This case illustrates the opportunity of considering metastatic
      thyroid carcinoma to skin even in cases which lack the classic cytologic and
      architectural features of papillary thyroid carcinoma follicular variant.

PMID- 23167300
TI  - Current pharmacotherapy options for gastritis.
AB  - INTRODUCTION: Gastritis is a broad term, which is used for different conditions
      by clinicians, endoscopists and pathologists. Classification strategies have led
      to more congruence between specialists. The histological evaluation of the
      gastric mucosa is mandatory for diagnosing and classifying gastritis. Main
      aetiologic factor is infection with Helicobacter pylori. The clinical importance
      of gastritis lays in the fact that it predisposes to more pronounced damage to
      the gastric mucosa, in particular peptic ulcer disease, and eventually atrophic
      gastritis, intestinal metaplasia and gastric malignancy, both adenocarcinoma and
      MALT lymphoma. AREAS COVERED: This review covers the current pharmacotherapy
      options for different forms of gastritis. The main focus is on H. pylori-induced
      gastritis. Thereafter, other forms of gastritis like autoimmune gastritis and non
      steroidal anti-inflammatory drug (NSAID)-related gastropathy are covered. EXPERT
      OPINION: The emerging problem of antibiotic resistance requires an accurate
      knowledge of local eradication rates. Standard triple therapy should be abandoned
      in regions with high clarithromycin resistance. In these areas, sequential or
      quadruple therapy is best initial treatment. Further research should focus on non
      invasive and effective techniques of susceptibility testing, making a tailored
      and cost-effective approach. Primary prevention of NSAID-related gastropathy can
      be enhanced by better education for clinicians and patients, so that both right
      prescription of gastroprotective agents as therapy adherence will improve.

PMID- 23167301
TI  - Haematopoietic stem cell transplantation for SCID patients: where do we stand?
AB  - Severe combined immunodeficiencies (SCIDs) correspond to the most severe form of
      primary immunodeficiency. The extreme severity of the clinical presentation in
      SCID has legitimately led physicians to consider these conditions as medical
      emergencies. Hundreds of patients worldwide have undergone allogeneic
      haematopoietic stem cell transplantation (HCST) in the last 40 years. The
      complete absence of the T cell compartment in SCID prompted the development
      (starting in the early 1980s) of haploidentical, parental HSCT for the many
      patients who do not have a human leucocyte antigen (HLA)-identical sibling.
      Despite the undeniable progress made in this field over recent years, the long
      lasting immunodeficiency that follows partially HLA-incompatible transplantation
      is still responsible for a mortality rate of 30% at one year post
      transplantation. New approaches for reconstituting T cell compartments more
      rapidly are under intense preclinical development and are discussed herein.

PMID- 23167302
TI  - Vital dysfunctions after intensive care discharge: prevalence and impact on
      patient outcome.
AB  - BACKGROUND: Patients discharged from the intensive care unit (ICU) are at
      increased risk for serious adverse events (SAEs). Recording vital functions and
      comprehending the consequences of altered vitals on general wards may be
      suboptimal. This potentially endangers recovery after successful intensive care.
      We aimed to determine the prevalence of vital dysfunctions after ICU discharge
      and their effect on patient outcome. METHODS: A prospective observational study.
      Adult patients discharged from a tertiary referral hospital ICU to general wards
      without treatment limitations were visited 24 h afterwards; their vitals were
      measured and reported to ward staff. Attending ward nurse responsible for patient
      was interviewed. RESULTS: The cohort consisted of 184 patients who had survived
      the first 24 h on the ward without complications (age: 57 +/- 16 years; male:
      68%). The prevalence of objectively measured vital dysfunctions was 15%, and the
      attending nurse had been unusually concerned about the patient in 19% of cases.
      Of the 184 patients, 9.8% subsequently suffered an SAE. In a multivariate
      logistic regression model, only vital dysfunctions (odds ratio 3.79; 95%
      confidence interval 1.18-12.2) and nurse concern (3.63; 1.17-11.3) were
      independently associated with an increased incidence of SAE. Medical emergency
      team (MET) assistance was never considered necessary by ward staff. Sensitivity
      of observed altered vitals on SAEs was 50% and specificity 89%. Sensitivity of
      nurse concern was 26%, specificity 84%. CONCLUSIONS: Simple vital function
      measurement and attending ward nurse's subjective assessment facilitate early
      detection of post-ICU patients at risk. The threshold in seeking assistance
      through MET remains high.

PMID- 23167303
TI  - Design, development and optimization of oral colon targeted drug delivery system
      of azathioprine using biodegradable polymers.
AB  - The present study was aimed at designing a microflora triggered colon targeted
      drug delivery system (MCDDS) based on swellable polysaccharide, Sterculia gum in
      combination with biodegradable polymers with a view to specifically deliver
      azathioprine in the colonic region for the treatment of IBD with reduced systemic
      toxicity. The microflora degradation properties of Sterculia gum was investigated
      in rat caecal phosphate buffer medium. The polysaccharide tablet cores were
      coated to different film thicknesses with blends of Eudragit RLPO and chitosan
      and overcoated with Eudragit L00 to provide acid and intestinal resistance.
      Swelling and drug release studies were carried out in simulated gastric fluid,
      SGF (pH 1.2), simulated intestinal fluid, SIF (pH 6.8) and simulated colonic
      fluid, SCF (pH 7.4 under anaerobic environment), respectively. Drug release study
      in SCF revealed that swelling force of the Sterculia gum could concurrently drive
      the drug out of the polysaccharide core due to the rupture of the
      chitosan/Eudargit coating in microflora activated environment. The degradation of
      chitosan was the rate-limiting factor for drug release in the colon. Drug release
      from the MCDDS was directly proportional to the concentration of the pore former
      (chitosan), but inversely related to the Eudragit RLPO coating thickness. 

PMID- 23167304
TI  - The discovery of a new class of synaptic transmitters in smooth muscle 50 years
      ago and amelioration of coronary artery thrombosis.
AB  - Clopidogrel and ticagrelor, antagonists to P2Y(12) receptor molecules on platelet
      membranes, significantly ameliorate acute myocardial infarction due to coronary
      artery thrombosis, the most common cause of death in the developed world. A
      personal account is given here of the foundational research that lead to the
      identification of P2Y receptors, carried out 50 years ago in the Melbourne
      University Zoology Department headed by Geoffrey Burnstock. In Christmas 1962, I
      made the serendipitous observation of large hyperpolarizing changes across the
      membranes of smooth muscle cells in the taenia coli of the intestine on
      stimulating its nerve supply. I then showed that these potentials relaxed the
      muscle and were not due to noradrenaline or acetylcholine, which were then the
      only substances known to be released from nerves. I called these non-adrenergic,
      non-cholinergic (NANC) terminals in the laboratory and showed that this NANC
      transmitter acted at receptor molecules on the muscle cells, promoting efflux of
      potassium ions, and so the observed potential changes. In 1968, Graeme Campbell
      showed that ATP relaxed the taenia coli muscle, and in 1969, David Satchell,
      using purine chromatography, showed that ATP was likely to be released from NANC
      terminals. The receptor molecules involved were shown to be exceptionally
      sensitive to 2-methylthio-ATP (Satchell and Macguire, 1975, J Pharmacol Exp Ther,
      195, 540), and so belonged to the class P2Y receptors as designated by Abbracchio
      and Burnstock, with subclasses P2Y(1)-P2Y(12). The discovery of the role of
      P2Y(12) receptors in increasing thrombosis lead to the focused research that
      resulted in clopidogrel and ticagrelor.

PMID- 23167305
TI  - Sex differences in decreased limbic and cortical grey matter volume in cocaine
      dependence: a voxel-based morphometric study.
AB  - Structural neuroimaging studies have provided evidence of differences in local
      brain volume between cocaine-dependent and healthy control individuals. While sex
      differences in aetiology, course and brain dysfunction associated with chronic
      cocaine abuse have been previously documented, evidence of sex-specific
      differences in brain volume has not been examined thus far. This study examined
      sex-related differences in grey matter volume between cocaine-dependent and
      healthy control subjects using voxel-based morphometry. High-resolution T1
      structural scans were obtained from 36 inpatient, treatment-engaged 3-week
      abstinent cocaine-dependent (CD) individuals. Fifty healthy control subjects were
      also scanned. Segmentation and registration were performed in SPM8, using New
      Segment and DARTEL, respectively. The whole-brain statistical analysis was
      conducted in SPM8 using random field-based cluster-size testing and family-wise
      error rate correction for multiple comparisons. CD patients were found to have
      less grey matter volume in anterior prefrontal cortex, including frontopolar and
      orbitofrontal cortices, and a posterior region surrounding the parietal-occipital
      sulcus. Female CD patients had less grey matter volume than female controls in
      left inferior frontal gyrus, insula, superior temporal gyrus and hippocampus.
      Male CD patients had less grey matter in a superior cortical region that included
      the precentral gyrus and the mid-cingulate. These sex differences in lower grey
      matter volume add to the evidence from functional neuroimaging for sex-specific
      differences in the neurophysiological changes associated with chronic cocaine
      use.

PMID- 23167307
TI  - Efficacy of cetuximab in the treatment of squamous cell carcinoma.
AB  - BACKGROUND: Cutaneous squamous cell carcinomas (CSCC) are very common. Localized
      CSCC are cured by surgery and/or radiotherapy and have a better prognosis than
      locally inoperable advanced CSCC. Cetuximab has recently been proposed to treat
      locally advanced CSCC when surgery or radiotherapy cannot be offered. OBJECTIVE:
      The authors report results of a pilot study conducted in inoperable CSCC patients
      treated with cetuximab alone or combined with chemotherapy or radiotherapy.
      MATERIAL AND METHODS: This study was conducted in 20 CSCC patients. RECIST
      criteria were used to evaluate clinical and radiological responses. RESULTS: Five
      patients received cetuximab associated with radiotherapy (CR), nine with
      carboplatin (CC) and six as monotherapy (CM) over 1-month cycle treatment.
      Response to treatment was evaluated every two cycles. After 2 months of
      treatment, the authors observed nine partial responses, six stabilizations and
      four progressions. Disease control rate was of 78% (100% for CR, 87.5% for CC and
      50% for CM) with a 47% response rate (80% for CR, 37.5% for CC and 33% for CM).
      CONCLUSION: The authors confirm the potential interest of cetuximab to treat
      unresectable advanced CSCC alone or combined with CC and CM. These results
      justify discussing a further randomized study combining radiotherapy and
      cetuximab.

PMID- 23167306
TI  - Plant polyadenylation factors: conservation and variety in the polyadenylation
      complex in plants.
AB  - BACKGROUND: Polyadenylation, an essential step in eukaryotic gene expression,
      requires both cis-elements and a plethora of trans-acting polyadenylation
      factors. The polyadenylation factors are largely conserved across mammals and
      fungi. The conservation seems also extended to plants based on the analyses of
      Arabidopsis polyadenylation factors. To extend this observation, we systemically
      identified the orthologs of yeast and human polyadenylation factors from 10 plant
      species chosen based on both the availability of their genome sequences and their
      positions in the evolutionary tree, which render them representatives of
      different plant lineages. RESULTS: The evolutionary trajectories revealed several
      interesting features of plant polyadenylation factors. First, the number of genes
      encoding plant polyadenylation factors was clearly increased from "lower" to
      "higher" plants. Second, the gene expansion in higher plants was biased to some
      polyadenylation factors, particularly those involved in RNA binding. Finally,
      while there are clear commonalities, the differences in the polyadenylation
      apparatus were obvious across different species, suggesting an ongoing process of
      evolutionary change. These features lead to a model in which the plant
      polyadenylation complex consists of a conserved core, which is rather rigid in
      terms of evolutionary conservation, and a panoply of peripheral subunits, which
      are less conserved and associated with the core in various combinations, forming
      a collection of somewhat distinct complex assemblies. CONCLUSIONS: The multiple
      forms of plant polyadenylation complex, together with the diversified polyA
      signals may explain the intensive alternative polyadenylation (APA) and its
      regulatory role in biological functions of higher plants.

PMID- 23167308
TI  - Is socket healing conditioned by buccal plate thickness? A clinical and
      histologic study 4 months after mineralized human bone allografting.
AB  - OBJECTIVE: The aim of this study was to clinically and histologically analyze the
      healing of grafted sockets by mineralized human bone allograft (MHBA) and
      nongrafted sockets, correlating the results with buccal plate thickness. MATERIAL
      AND METHODS: Thirty-one sockets were randomly split into control (CG) and
      treatment (MHBA grafted) (TG) groups and, subsequently, into four subgroups
      according to buccal plate thickness: a <= 1 mm and b > 1 mm. Ridge thickness,
      depth, and height were monitored. Four months after, at implant placement, a bone
      core biopsy for histologic and morphometric analyses was taken. RESULTS: The
      differences of buccal height (TG-a -0.27 and CG-a -1.17 mm) and width (TG-a 0.55
      and CG-a 2.67 mm, TG-b 0.12 and CG-b 1.17 mm) were statistically significant. The
      increase in bone amount CG-b (28.17%) compared with CG-a (16.98%) was
      statistically significant. Soft tissue amount of TG-b (54.21%) and TG-a (56.91%)
      was lower than that of CG-b (71.83%) and CG-a (83.01%), both being statistically
      significant (P = 0.002). CONCLUSIONS: The results proved that thin buccal plates
      had a worse outcome on socket healing and that network formation by MBHA not only
      predisposes a successful implant insertion but also acts as size keeper.

PMID- 23167309
TI  - Does take-home analgesia improve postoperative pain after elective day case
      surgery? A comparison of hospital vs parent-supplied analgesia.
AB  - BACKGROUND: More children are undergoing same-day surgery. While advances have
      been made in pediatric pain management, there have been few studies addressing
      pain management in the home (Br J Anaesth, 82, 1999 and 319). We wished to
      investigate whether issuing parents with take-home analgesia would improve
      postoperative pain scores and/or parental satisfaction following hospital
      discharge. METHODS: Two hundred children, and their parents, attending for day
      case surgery at our institution were randomized into two groups. One group
      received advice regarding the management of postoperative pain and were given a
      pack containing discharge medications: group 'dispensed'. The other group
      received the same advice, but did not receive any medication: group 'advised'.
      Telephone interviews were conducted to assess pain scores, PONV, functional
      activity, analgesia requirements, and satisfaction rates. RESULTS: Data were
      available for 181 patients (median age, 4 years; range, 0-12 years): 89 children
      in group 'dispensed' and 92 children in group 'advised'. Postoperative
      instructions were followed by 86% in group 'advised' and 89% in group 'dispensed'
      (P = 0.68). Although all parents received analgesia advice, only 85/181 (48%)
      recalled the information. Rates for no/mild pain and moderate/severe pain were
      similar between the two groups: 59% (group 'advised') vs 62% (group 'dispensed')
      and 41% (group 'advised') vs 38% (group 'dispensed') (P = 0.78). DISCUSSION: Our
      study did not show any differences in the incidence of pain/parental satisfaction
      between the two groups. Analgesia advice given to parents was poorly retained,
      suggesting that other methods for disseminating information should be considered.

PMID- 23167311
TI  - Enhancing child survival and development in lower- and middle-income countries by
      achieving population-level behavior change.

PMID- 23167310
TI  - Economic benefits of subcutaneous rapid push versus intravenous immunoglobulin
      infusion therapy in adult patients with primary immune deficiency.
AB  - OBJECTIVE: The objective of this study is to evaluate the economic benefits of
      immunoglobulin replacement therapy achieved subcutaneously (subcutaneous
      immunoglobulin, SCIG) by the rapid push method compared to intravenous infusion
      therapy (intravenous immunoglobulin, IVIG) in primary immune deficiency (PID)
      patients from the healthcare system perspective in the context of the adult SCIG
      home infusion program based at St Paul's Hospital, Vancouver, Canada. MATERIALS
      AND METHODS: SCIG and IVIG options were compared in cost-minimisation and budget
      impact models (BIMs) over 3 years. Sensitivity analyses were performed for both
      models to evaluate the impact of varying modality of IVIG treatments and
      proportion of patients switching from IVIG to SCIG. RESULTS: The cost
      minimisation model estimated that SCIG treatment reduced cost to the healthcare
      system per patient of $5736 over 3 years, principally because of less use of
      hospital personnel. This figure varied between $5035 and $8739 depending on
      modality of IVIG therapy. Assuming 50% of patients receiving IVIG switched to
      SCIG, the BIM estimated cost savings for the first 3 years at $1.308 million or
      37% of the personnel and supply budget. These figures varied between $1.148
      million and $2.454 million (36 and 42%) with varying modalities of IVIG therapy.
      If 75% of patients switched to SCIG, the reduced costs reached $1.962 million or
      56% of total budget. CONCLUSION: This study demonstrated that from the health
      system perspective, rapid push home-based SCIG was less costly than hospital
      based IVIG for immunoglobulin replacement therapy in adult PID patients in the
      Canadian context.

PMID- 23167312
TI  - Oral health literacy: a workshop.

PMID- 23167314
TI  - Residual CO2 trapping in Indiana limestone.
AB  - We performed core flooding experiments on Indiana limestone using the porous
      plate method to measure the amount of trapped CO(2) at a temperature of 50 
      degrees C and two pressures: 4.2 and 9 MPa. Brine was mixed with CO(2) for
      equilibration, then the mixture was circulated through a sacrificial core.
      Porosity and permeability tests conducted before and after 884 h of continuous
      core flooding confirmed negligible dissolution. A trapping curve for
      supercritical (sc)CO(2) in Indiana showing the relationship between the initial
      and residual CO(2) saturations was measured and compared with that of gaseous
      CO(2). The results were also compared with scCO(2) trapping in Berea sandstone at
      the same conditions. A scCO(2) residual trapping end point of 23.7% was observed,
      indicating slightly less trapping of scCO(2) in Indiana carbonates than in Berea
      sandstone. There is less trapping for gaseous CO(2) (end point of 18.8%). The
      system appears to be more water-wet under scCO(2) conditions, which is different
      from the trend observed in Berea; we hypothesize that this is due to the greater
      concentration of Ca(2+) in brine at higher pressure. Our work indicates that
      capillary trapping could contribute to the immobilization of CO(2) in carbonate
      aquifers.

PMID- 23167315
TI  - Patterns of mortality in public and private hospitals of Addis Ababa, Ethiopia.
AB  - BACKGROUND: Ethiopia is encountering a growing burden of non-communicable
      diseases along with infectious diseases, perinatal and nutritional problems that
      have long been considered major problems of public health importance. This
      retrospective analysis was carried out to examine the mortality patterns from
      communicable diseases and non communicable diseases in public and private
      hospitals of Addis Ababa. METHODS: Approximately 47,153 deaths were captured over
      eight years (2002-2010) in forty three public and private hospitals of Addis
      Ababa, Ethiopia. Data collectors (43 hospital clerks) and coordinators (3 nurses)
      had been extensively trained on how to review hospital death records. Information
      obtained included: dates of admission and death, age, sex, address, and principal
      cause of death. Only the diseases responsible for deaths are taken as the cause
      of death. Cause of death was coded using International Classification of Diseases
      (ICD-10) and data were double entered. Diseases were classified into: Group I
      (communicable diseases, maternal conditions and nutritional deficiencies); Group
      II (non-communicable causes); and Group III (injuries). Percentages, proportional
      mortality ratios, 95% confidence intervals (CI) and Adjusted odd ratios (OR) were
      calculated. RESULTS: Overall, 59% of the deaths were attributed to Group I
      diseases, and 31% to Group II diseases and 12% to injuries. Nearly 56% of the
      males and 68% of the females deaths were due to five leading causes (conditions
      arising during perinatal period, HIV/AIDS, tuberculosis, cardiovascular diseases
      and respiratory infections). Significantly larger proportions of females died
      from Group I (67%) and Group II diseases (32%) compared with males (where the
      respective proportions were 52% and 30%). Significantly higher proportion of
      males (17%) than females (6%) were dying from Group III diseases. Deaths due to
      Group I diseases decreased while those due to Group II diseases increased with
      age. Overall Group I diseases and HIV/AIDS, tuberculosis and still birth
      mortality in particular have showed decreasing trend while Group II and III
      increasing over time. Double burden in mortality was highly observed in the age
      groups of 15-64 years. Those aged >45 years were dying more likely with non
      communicable diseases compared with children. Children aged below 15 years were
      16 times more likely to die from communicable, perinatal and nutritional
      conditions compared with elders. Mortality variation with age has been identified
      between public and private hospitals. CONCLUSIONS: The results of the present
      study shows that, in addition to the common Group I causes of death, emerging
      group II diseases are contributing to high proportions of mortality in the public
      and private hospitals of Addis Ababa, Ethiopia. Thus, priority should be given to
      the prevention and management of conditions arising during perinatal period such
      as low birth weight and still birth, HIV/AIDS; tuberculosis, respiratory
      infections, cardiovascular diseases, malignant neoplasm, chronic respiratory
      diseases and road traffic accident. The planning of health resources and
      activities should take into account the double burden in mortality due to Group I
      and Group II diseases. This calls for strengthening approaches towards the
      control and prevention of non-communicable diseases such as cardiovascular and
      malignant neoplasm.

PMID- 23167316
TI  - Delayed rupture of left ventricular apex after heart transplantation: diagnosis
      by two- and three-dimensional transthoracic echocardiography.

PMID- 23167317
TI  - Molecular involvement and prognostic importance of fms-like tyrosine kinase 3 in
      acute myeloid leukemia.
AB  - AML (Acute myeloid leukemia) is a form of blood cancer where growth of myeloid
      cells occurs in the bone marrow. The prognosis is poor in general for many
      reasons. One is the presence of leukaemia-specific recognition markers such as
      FLT3 (fms-like tyrosine kinase 3). Another name of FLT3 is stem cell tyrosine
      kinase-1 (STK1), which is known to take part in proliferation, differentiation
      and apoptosis of hematopoietic cells, usually being present on haemopoietic
      progenitor cells in the bone marrow. FLT3 act as an independent prognostic factor
      for AML. Although a vast literature is available about the association of FLT3
      with AML there still is a need of a brief up to date overview which draw a clear
      picture about this association and their effect on overall survival.

PMID- 23167318
TI  - Current status of knowledge, attitude and practice (KAP) and screening for
      cervical cancer in countries at different levels of development.
AB  - Cancer of the uterine cervix is a worldwide menace taking innumerable womens'
      lives. The literature is vast and a large number of studies have been conducted
      in this field. Analyses have shown significant differences exist in terms of
      screening and HPV testing facilities among high income and low to middle income
      countries. In addition, acute lack of awareness and knowledge among the concerned
      population is particularly noted in rural areas of the low income countries. A
      detailed review of Indian case studies revealed that early age of marriage and
      childbirth, multiparity, poor personal hygiene and low socio-economic status
      among others are the principal risk factors for this disease. This review
      concludes that a two pronged strategy involving strong government and NGO action
      is necessary to minimize the occurrence of cervical cancer especially in low and
      medium income countries.

PMID- 23167319
TI  - Omics of cancer.
AB  - With the advances in modern diagnostic expertise for cancer, certain approaches
      allowing scanning of the complete genome and the proteome are becoming very
      useful for researchers. These high throughput techniques have already proven
      power, over traditional detection methods, in differentiating disease sub-types
      and identifying specific genetic events during progression of cancer. This paper
      introduces major branches of omics-technology and their applications in the field
      of cancer. It also addresses current road blocks that need to be overcome and
      future possibilities of these methods in oncogenic detection.

PMID- 23167320
TI  - Reliability and validity of the quality of life -family version (QOL-FV) in
      Turkish family caregivers of patients with cancer.
AB  - OBJECTIVES: Family caregivers (FCs) are often the primary source of social and
      emotional support for cancer patients and play a major role in how well they
      manage their illness. The aim of this study was to create an Turkish version of
      the Quality of Life - Family Version (QOL-FV) and to evaluate its psychometric
      properties in a sample of FCs of cancer patients. MATERIALS AND METHODS: This
      study was carried out with the FCs of 218 patients with cancer. Data were
      collected with a Demographic Questionnaire and the QOL-FV and The
      Multidimentional Scale of Perceived Social Support (MSPSS). The QOL-FV was
      developed by Ferrell and Grant and is composed of 4 subdimensions. Linguistic
      validity, translation, back translation, and content validity were tested with
      expert opinions. Test-retest reliability, and internal consistency reliability
      were assessed. Construct validity was tested by factor analysis and with the
      scale of the MSPSS. RESULTS: The family caregivers were between the ages of 46-56
      (32.6%), a great number of them being male (52.8%). The scale is made up of four
      subdimensions. The result of the test-retest analysis of this scale was
      calculated as r:0.86. As a result of the reliability analysis, six items were
      eliminated from the scale, factor analyses were fulfilled according to varimax
      transformation through the method of principal components. Four new subdimensions
      were restrustured at the end of the analysis. The scale of Cronbach
      alphacoefficient was calculated as 0.90. Concurrent validity showed low
      correlations with the MSPSS (r=0.29). CONCLUSIONS: The QOL-FV, adapted into
      Turkish, was found to have sufficient reliability and validity.

PMID- 23167321
TI  - Serum kynurenic acid: possible association with invasiveness of non-small cell
      lung cancer.
AB  - The lung adenocarcinoma is considered more aggressive than other types of non
      small cell lung cancer. As metabolites of tryptophan degradation along the
      kynurenine pathway, including kynurenic acid, have been shown to induce
      immunosuppression and facilitate escape of tumor cells from immune surveillance,
      a hypothesis was set up that differences in biological behavior between types of
      lung cancer may be associated with altered activity of the kynurenine metabolic
      pathway. The aim of the study was to determine kynurenic acid levels in the serum
      of patients with bronchial adenocarcinoma for comparison with other types of non
      small cell lung cancer. A total of 227 patients with non-small cell lung cancer
      were enrolled in the study, including 71 with adenocarcinoma and 96 with squamous
      cell carcinoma. Serum kynurenic acid concentration was determined with use of
      high performance liquid chromatography and fluorometry. The level of kynurenic
      acid in the serum of patients with adenocarcinoma was significantly higher than
      in those with squamous cell lung cancer (107.1 +/- 62.8 pmol/ml; 95%CI: 92.4 to
      132.3 pmol/ml versus 82.1 +/- 47.6 pmol/ml; 95%CI: 78.5 to 91.2 pmol/ml,
      respectively; p = 0.027). Differences between other histological types of lung
      cancer were insignificant. We conclude that increased activity of kynurenine
      metabolic pathway manifested by elevated serum kynurenic acid level may be one of
      the factors associated with clinically distinct biological behavior of
      adenocarcinoma, in particular high invasiveness and rapid progression.

PMID- 23167322
TI  - Prevalence of smoking among female medical students in Saudai Arabia.
AB  - BACKGROUND: Women make up half of the world's population, and comprise 20% of the
      world's one billion smokers. The aim of this study was to assess the prevalence
      of smoking among female medical students in comparison to female non-medical
      students, and to assess the importance of medical education and knowledge in
      decreasing the prevalence of smoking among female university students in Saudi
      Arabia. METHOD: We used a self-administered questionnaire to collect cross
      sectional data from a randomly selected sample of 320 female students attending
      King Abdul-Aziz University, Jeddah. Medical students comprised 50% of the sample.
      RESULTS: A total of 310 students (96.9%) completed and returned the
      questionnaire. The prevalence of smoking was higher in non-medical female
      students (4.2%) compared to medical female students (0.32%) (P < 0.001).
      CONCLUSION: The prevalence of smoking is low among female medical students
      compared to female non-medical students, presumably because of their awareness,
      level of education, and knowledge of the risks to health associated with smoking.
      Our study highlights the need for increased knowledge, health education, and
      awareness of the risks of smoking to reduce smoking among female university
      students.

PMID- 23167323
TI  - Association between trace element and heavy metal levels in hair and nail with
      prostate cancer.
AB  - While associations between trace elements and heavy metals with prostate cancer
      are still debatable, they have been considered as risk factors for prostate
      cancer. Thus, this study aimed to detect any links between selected minerals and
      heavy metals including Se, Zn, Cu, Mn and Fe with prostate cancer. A case control
      study was carried out among 100 subjects (case n=50, control n=50), matched for
      age and ethnicity. Trace elements and heavy metals level in hair and nail samples
      were determined by ICP-MS. Mean selenium levels in hair and nail of the cases
      were significantly lower as compared to controls. A similar trend was noted for
      zinc in both hair and nail samples, whereas the mean level of copper was
      significantly higher in cases than controls. Similar elevation was noted for iron
      and manganese (p<0.05 for all parameters). Low levels of selenium and zinc and
      high levels of copper, iron and manganese appear to be associated with the risk
      of prostate cancer. Further studies to elucidate the causal mechanisms and
      appropriate chemopreventive measures are needed.

PMID- 23167324
TI  - Radioimmunoimaging with mixed monoclonal antibodies of nude mice bearing human
      lung adenocarcinoma xenografts.
AB  - The present study was conducted to evaluate radioimmunoimaging (RII) and in vivo
      distribution of mixed antibodies 99mTc-EGFR-mAb and 99mTc-CD44- mAb in nude mice
      bearing human lung adenocarcinoma xenografts. Single and mixed applications of
      the two radiolabeled monoclonal antibodies (mAbs) were compared. Direct labeling
      of 99mTc was applied to radiolabel the EGFR and CD44 mAbs. The properties of the
      radiolabeled antibodies were then characterized. RII and assessment of the
      distribution of the antibodies in nude mice bearing lung adenocarcinoma
      xenografts were achieved by applying separate and combined doses of 99mTc-EGFR
      mAb and 99mTc-CD44-mAb. The labeling rates of 99mTc for EGFR-mAb and CD44-mAb
      were 91.5% +/-3.8% and 92.3% +/- 4.1% respectively, with specific activities of
      2.8 and 2.9 MBq/MUg, respectively, and radiochemical purities (RCP) of 96.5% and
      96.2%. The radioactivity uptake of the combined application of both radiolabeled
      antibodies was clearly higher than with a single application of either alone. The
      relative values of target-to-nontarget (T/ NT) measured through the regional
      interest (ROI) technique were 5.59 +/- 0.42 (mixed antibodies), 2.78 +/-0.20
      (99mTc-EGFR-mAb), and 2.28 +/- 0.16 (99mTc-CD44-mAb) in the RII. The body
      distribution of the radiolabeled antibodies and their imaging results were
      basically identical. Application of the mixed antibodies with 99mTc- EGFR-mAb and
      99mTc-CD44-mAb can increase the radioactivity uptake of tumor tissue, leading to
      more ideal target-to-nontarget ratios, and therefore superior results.

PMID- 23167326
TI  - Acceptance of human papillomavirus vaccine by adolescent girls and their parents
      in Turkey.
AB  - PURPOSE: The aim of this study was to identify the opinions of Turkish
      adolesecent girls and their parents about HPV vaccination and the consistency.
      METHODS: This descriptive study covered 301 girls and their parents.
      Questionnares were developed by the researchers based on findings within the
      literature and applied for data collection. RESULTS: The mean age was 19.4 for
      girls, 44.2 for mothers and 47.9 for fathers. It was found that 43.5 percent of
      girls and 31.9 percent of mothers wish to be vaccinated against HPV. Also, 45.5
      percent of mothers and 44.9 percent of fathers wish for their daughters to be
      vaccinated against HPV. A moderate consistency was found between mothers and
      fathers; a low consistency was found between fathers and girls, and between
      mothers and girls. CONCLUSIONS: the study indicates that an appropriate
      background has been partially provided about the acceptability of the vaccine
      between parents and their daughters in Turkey. However, the vast majority of
      adolescent girls and parents are indecisive or reluctant about HPV vaccination.
      This study also showed that the decisions of adolescents about vaccination may be
      affected by the opinions of the parents.

PMID- 23167325
TI  - A GFP-labeled human colon cancer metastasis model featuring surgical orthotopic
      implantation.
AB  - Colorectal cancer has become a major disease threatening human health. To
      establish animal models that exhibit the characteristics of human colorectal
      cancer will not only help to study the mechanisms underlying the genesis and
      development effectively, but also provide ideal carriers for the screening of
      medicines and examining their therapeutic effects. In this study, we established
      a stable, colon cancer nude mouse model highly expressing green fluorescent
      protein (GFP) for spontaneous metastasis after surgical orthotopic implantation
      (SOI). GFP- labeled colon cancer models for metastasis after SOI were
      successfully established in all of 15 nude mice and there were no surgery-related
      complications or deaths. In week 3, primary tumors expressing GFP were observed
      in all model animals under fluoroscopy and two metastatic tumors were monitored
      by fluorescent imaging at the same time. The tumor volumes progressively
      increased with time. Seven out of 15 tumor transplanted mice died and the major
      causes of death were intestinal obstruction and cachexia resulting from malignant
      tumor growth. Eight model animals survived at the end of the experiment, 6 of
      which had metastases (6 cases to mesenteric lymph nodes, 4 hepatic, 2 pancreatic
      and 1 mediastinal lymph node). Our results indicate that our GFP-labeled colon
      cancer orthotopic transplantation model is useful with a high success rate; the
      transplanted tumors exhibit similar biological properties to human colorectal
      cancer, and can be used for real-time, in vivo, non-invasive and dynamic
      observation and analysis of the growth and metastasis of tumor cells.

PMID- 23167327
TI  - Breast, cervical, and colorectal cancer screening status of a group of Turkish
      women.
AB  - INTRODUCTION: The aim of the study was to determine the breast, cervical, and
      colorectal cancer screening rates and the influencing factors in a group of
      Turkish females. METHODS: This descriptive study was conducted in a School of
      Nursing. The study sample consisted of 603 females who were the mothers/neighbors
      or relatives of the nursing students. Data collection forms were developed by the
      investigators after the relevant literature was screened and were used to collect
      the data. RESULTS: Of the women aged 30 and over, 32.8% had undergone a pap smear
      test at least once in their life. Of those aged 50 and over, 48.2% had undergone
      mammography at least once and FOBT had been performed in 12% of these women in
      their life. Having heard of the screening tests before, knowing why they are
      done, and having information on the national cancer screening program were
      important factors influencing the rates of women having these tests done.
      DISCUSSION: The results of this study show that the rates of women participating
      in national cervical, breast, and colorectal cancer screening programs are not at
      the desired levels. Having heard of the screening tests before, knowing why they
      are done, and having information on the national cancer screening program were
      important factors influencing the rates of women having these tests done. It is
      suggested that written and visual campaigns to promote the service should be used
      to educate a larger population, thus increasing the participation rates for
      cancer screening programs.

PMID- 23167328
TI  - Incidence and survival rates among pediatric osteogenic sarcoma cases in Khon
      Kaen, Thailand, 1985-2010.
AB  - BACKGROUND: Osteosarcoma is the most common bone cancer in children, responsible
      for a high rate of amputation and death. This is the first long-term, population
      based, epidemiologic and survival study in Thailand. OBJECTIVE: To study the
      incidence and survival rates of pediatric osteosarcoma in Khon Kaen. METHOD:
      Childhood osteosarcoma cases (0-19 years) diagnosed between 1985-2010 were
      reviewed. The data were retrieved from the population-based data set of the Khon
      Kaen Cancer Registry and medical records from Srinagarind Hospital, Faculty of
      Medicine, Khon Kaen University. All cases were censored until the end of April
      2012. The age-standardized incidence rate (ASR) was calculated using the standard
      method. Survival experience was analyzed using the standard survival function
      (STATA 9.0) and presented with a Kaplan-Meier curve. RESULTS: 58 cases were
      enrolled. The overall ASR was 14.1 per million. Males and females were equally
      affected. The peak incidence was for 15-19 year-olds in both sexes (ASR=10.4 per
      million in males and 8.5 in females). The 5-year overall survival rate was 27.6%
      (95% CI: 15.8-40.8%). The median survival time was 1.6 years (95% CI: 1.2-2.1).
      In a subgroup analysis, the patients who received only chemotherapy survived
      longer (5-year survival 45.7%, median survival time 4.1 years, p=0.12).
      CONCLUSION: The incidence rate for childhood osteosarcoma was slightly less than
      those reported for Western countries. The survival rate was also lower than
      reports from developed countries. Further evaluation of the treatment protocol
      and risk factor stratification is needed.

PMID- 23167329
TI  - Community-based cross-sectional study of carcinogenic human liver fluke in
      elderly from Surin province, Thailand.
AB  - BACKGROUND: Opisthorchis viverrini infection is a serious public-health problem
      in Southeast Asia. It is associated with a number of hepatobiliary diseases and
      the evidence strongly indicates that liver fluke infection is the etiology of
      cholangiocarcinoma. OBJECTIVES: This study aimed to determine Opisthorchis
      viverrini infection in elderly people in Surin province, Northeastern Thailand.
      METHODS: A community-based cross-sectional survey was conducted among 333 elderly
      in 17 districts of Surin province, during one year period from January to
      December 2011. O. viverrini infection was determined using Kato's Thick Smear
      technique and socio-demographic were collected using predesigned semi-structured
      questionnaires, respectively. RESULTS: A total of 333 elderly including 116 males
      and 217 females were selected from different study sites. Overall intestinal
      parasitic infection was 16.2%, predominantly in O. viverrini (9.91%) and followed
      by Strongyloides stercolaris (4.80%) and hookworm (1.50%), respectively. The O.
      viverrini infection was found higher in males (13.8%) than females (7.83%), and
      frequently in elderly 60-70 year old with 14.2%. Chi-square testing indicated
      that education and occupation were significantly associated with O. viverrini
      infection (P value = 0.02). The distribution of O. viverrini infection was found
      in 11 districts which was covered 64.7% of the studies areas. The highest
      prevalence was found in Thatum with 39.1%, and followed by Sangkha (24.0%),
      Buachet (21.1%), Samrong Thap (19.1%), Si Narong (15.0%), and Ratanaburi (13.3%)
      districts. CONCLUSION: This findings stress that O viverrini is still a problem
      in Thailand. We confirmed, for the first time, the high endemicity of human O.
      viverrini infections in elderly in Surin province of Thailand, underlying the
      fact that mass treatment and health education are urgently required.

PMID- 23167330
TI  - Understanding breast cancer screening practices in Taiwan: a country with
      universal health care.
AB  - While the incidence of breast cancer (BC) has been relatively low in Asian
      countries, it has been rising rapidly in Taiwan. Within the last decade, it has
      replaced cervical cancer as the most diagnosed cancer site for women.
      Nevertheless, there is a paucity of studies reporting the attitudes and practices
      of breast cancer screening among Chinese women. The aim of this study is to
      assess Taiwanese women's knowledge of and attitudes toward BC screening and to
      identify potential factors that may influence screening behavior. The study
      population consisted of a sample of 434 Taiwanese women aged 40 and older.
      Despite access to universal health care for Taiwanese women and the fact that a
      majority of the women had heard of the breast cancer screening (mammogram,
      clinical breast exams, etc.), the actual utilization of these screening
      modalities was relatively low. In the current study, the majority of women had
      never had mammograms or ultrasound in the past 5 years. The number one most
      reported barriers were "no time, " "forgetfulness, " "too cumbersome, " and
      "laziness, " followed by the perception of no need to get screened. In addition,
      the results revealed several areas of misconceptions or incorrect information
      perceived by study participants. Based on the results from the regression
      analysis, significant predictors of obtaining repeated screening modalities
      included age, coverage for screening, barriers, self-efficacy, intention,
      family/friends diagnosed with breast cancer. The findings from the current study
      provide the potential to build evidence-based programs to effectively plan and
      implement policies in order to raise awareness in breast cancer and promote BC
      screening in order to optimize health outcomes for women affected by this
      disease.

PMID- 23167331
TI  - Human embryonic stem cells--a potential vaccine for ovarian cancer.
AB  - OBJECTIVE: To investigate the therapeutic potential of human embryonic stem cells
      (hESCs) as a vaccine to induce an immune response and provide antitumor
      protection in a rat model. METHODS: Cross-reactivity of antigens between hESCs
      and tumour cells was screened by immunohistochemistry. Fischer 344 rats were
      divided into 7 groups, with 6 rats in each, immunized with: Group 1, hESC; Group
      2, pre-inactivated mitotic NuTu-19; Group 3 PBS; Group 4, hESC; Group 5, pre
      inactivated mitotic NuTu-19; Group 6, PBS; Group 7, hESC only. At 1 (Groups 1-3)
      or 4 weeks (Groups 4-6) after the last vaccination, each rat was challenged
      intraperitoneally with NuTu-19. Tumor growth and animal survival were closely
      monitored. Rats immunized with H9 and NuTu- 19 were tested by Western blot
      analysis of rat orbital venous blood for cytokines produced by Th1 and Th2 cells.
      RESULTS: hESCs presented tumour antigens, markers, and genes related to tumour
      growth, metastasis, and signal pathway interactions. The vaccine administered to
      rats in Group 1 led to significant antitumor responses and enhanced tumor
      rejection in rats with intraperitoneal inoculation of NuTu-19 cells compared to
      control groups. In contrast, rats in Group 4 did not display any elevation of
      antitumour responses. Western blot analysis found cross-reactivity among
      antibodies generated between H9 and NuTu-19. However, the cytokines did not show
      significant differences, and no side effects were detected. CONCLUSION: hESC
      based vaccination is a promising modality for immunotherapy of ovarian cancer.

PMID- 23167332
TI  - Concurrent weekly cisplatin versus triweekly cisplatin with radiotherapy in the
      treatment of cervical cancer: a meta-analysis result.
AB  - AIMS: To evaluate the adverse effect and survival outcome of weekly and triweekly
      cisplatin with radiotherapy in treatment of cervical cancer. METHODS: After an
      extensive literature search between 1995-2011,we analyzed 7 studies to compare
      weekly cisplatin and triweekly cisplatin combined radiotherapy. RESULTS: Our
      analysis established that weekly cisplatin has a lower risk of hematologic
      toxicity than triweekly cisplatin with concurrent radiotherapy in the treatment
      of cervical cancer. However, there were no differences in progression free
      survival and overall survival between weekly cisplatin and triweekly cisplatin
      (p>0.05). CONCLUSIONS: Weekly cisplatin combined with concurrent radiation has
      lower risk in hematologic toxicity than triweekly cisplatin, but does not improve
      survival. Triweekly cisplatin treatment has longer intervals and is therefore
      more convenient. Clinicians and patients can choose either weekly cisplatin or
      triweekly cisplatin combined radiotherapy for cervical cancer.

PMID- 23167333
TI  - Association between TP53 Arg72Pro polymorphism and hepatocellular carcinoma risk:
      a meta-analysis.
AB  - BACKGROUND: Previous studies on the association between the TP53 Arg72Pro
      polymorphism and hepatocellular carcinoma (HCC) risk obtained controversial
      findings. This study aimed to quantify the strength of the association by meta
      analysis. METHODS: We searched PubMed and Wangfang databases for published
      studies on the association between the TP53 Arg72Pro polymorphism and HCC risk,
      using the pooled odds ratio (OR) with its 95% confidence intervals (95% CI) for
      assessment. RESULTS: 10 studies with a total of 2,026 cases and 2,733 controls
      were finally included into this meta-analysis. Overall, the TP53 Arg72Pro
      polymorphism was not associated with HCC risk (all P values greaterth HCC risk in
      Caucasians in three genetic models (For Pro versus Arg, OR = 1.20, 95%CI 1.03
      1.41; For ProPro versus ArgArg, OR = 1.74, 95%CI 1.23-2.47; For ProPro versus
      ArgPro/ArgArg, OR = 1.85, 95%CI 1.33-2.57). However, there was no significant
      association between the TP53 Arg72Pro polymorphism and HCC risk in East Asians
      (all P values greater than 0.10). No evidence of publication bias was observed.
      CONCLUSION: Meta-analyses of available data suggest an obvious association
      between the TP53 Arg72Pro and HCC risk in Caucasians. However, the TP53 Arg72Pro
      polymorphism may have a race-specific effect on HCC risk and further studies are
      needed to elucidate this possible effect.

PMID- 23167334
TI  - Posttraumatic growth and social support in Turkish patients with cancer.
AB  - Posttraumatic growth (PTG) is the experience of positive change that occurs as a
      result of the struggle with highly challenging life crises. The need to
      understand PTG in relation to actual changes in an individual's life has recently
      been raised. Little is known about the role of social support in the experience
      of positive outcomes. The purpose of this study is to investigate the role of
      perceived social support in enhancing PTG in cancer patients. This study involved
      105 cancer patients. The data were collected using a questionnaire that
      determined the socio-demographic features, posttraumatic growth inventory (PTGI)
      and perceived social support. Participants reported relatively high levels of PTG
      and social support. Total perceived social support, support from family, and
      friends were significantly positive associated with the development of PTG among
      cancer patients. Accordingly, the social surroundings of the patient should be
      informed about the importance of social support and how it helps the patient;
      they should be made aware of necessity of social support.

PMID- 23167335
TI  - MDM2 T309G has a synergistic effect with P21 ser31arg single nucleotide
      polymorphisms on the risk of acute myeloid leukemia.
AB  - BACKGROUND: The P53 tumor suppressor gene plays a pivotal role in maintaining
      cellular homeostasis by preventing the propagation of genome mutations. P53 in
      its transcriptionally active form is capable of activating distinct target genes
      that contribute to either apoptosis or growth arrest, like P21. However, the MDM2
      gene is a major negative regulator of P53. Single nucleotide polymorphisms (SNP)
      in codon Arg72Pro of P53 results in impairment of the tumor suppressor activity
      of the gene. A similar effect is caused by a SNP in codon 31 of P21. In contrast,
      a SNP in position 309 of MDM2 results in increased expression due to substitution
      of thymine by guanine. All three polymorphisms have been associated with
      increased risk of tumorigenesis. AIM OF THE STUDY: We aimed to study the
      prevalence of SNPs in the P53 pathway involving the three genes, P53, P21 and
      MDM2, among acute myeloid leukemia (AML) patients and to compare it to apparently
      normal healthy controls for assessment of impact on risk. RESULTS: We found that
      the P21 ser31arg heterozygous polymorphism increases the risk of AML (P
      value=0.017, OR=2.946, 95% CI=1.216-7.134). Although the MDM2 309G allele was
      itself without affect, it showed a synergistic effect with P21 ser/arg
      polymorphism (P value=0.003, OR= 6.807, 95% CI= 1.909-24.629). However, the MDM2
      309T allele abolish risk effect of the P21 polymorphic allele (P value= 0.71).
      There is no significant association of P53 arg72pro polymorphism on the risk of
      AML. CONCLUSION: We suggest that SNPs in the P53 pathway, especially the P21
      ser31arg polymorphism and combined polymorphisms especially the P21/ MDM2 might
      be genetic susceptibility factors in the pathogenesis of AML.

PMID- 23167336
TI  - Awareness of general public towards cancer prostate and screening practice in
      Arabic communities: a comparative multi-center study.
AB  - The current study aimed at exploring the knowledge and beliefs of men aged forty
      years and over towards prostate cancer screening and early detection in three
      Arab countries. The field work was conducted in three countries; Saudi Arabia,
      Egypt and Jordan, during the period February through December 2011. Our target
      population were men aged 40 years and over. It was a population-based cross
      sectional study comprising 400 subjects at each site. In addition to socio
      demographic data, history of the present and past medical illness, practice
      history of prostatic cancer examination, family history of cancer prostate;
      participants were inquired about their knowledge and attitude towards prostate
      cancer and screening behavior using two different likert scales. The percentage
      of participants who practiced regular prostate check up ranged from 8-30%. They
      had poor knowledge and fair attitude towards prostate cancer screening behavior,
      where the mean total knowledge score was 10.25+/-2.5, 10.76+/-3.39 and 11.24+/
      3.39 whereas the mean total attitude score was 18.3+/-4.08, 20.68+/-6.4 and
      17.96+/-5.3 for Saudi Arabia, Egypt and Jordan respectively. The respondents
      identified the physicians as the main sources of this information (62.4%), though
      they were not the main motives for regular checkup. Knowledge was the only
      significant predictor for participants' attitude in the multiple regression
      models. Participants' attitudes depends mainly on level of knowledge and quantity
      of information provided to the patients and their families. Such attitudes should
      rely on a solid background of proper information and motivation from physicians
      to enhance and empower behaviors towards prostate cancer screening practices.

PMID- 23167337
TI  - Meta-analysis of associations between the MDM2-T309G polymorphism and prostate
      cancer risk.
AB  - The mouse double minute 2 (MDM2) gene plays a key role in the p53 pathway, and
      the SNP 309T/G single- nucleotide polymorphism in the promoter region of MDM2 has
      been shown to be associated with increased risk of cancer. However, no consistent
      results were found concerning the relationships between the polymorphism and
      prostate cancer risk. This meta-analysis, covering 4 independent case-control
      studies, was conducted to better understand the association between MDM2-SNP
      T309G and prostate cancer risk focusing on overall and subgroup aspects. The
      analysis revealed, no matter what kind of genetic model was used, no significant
      association between MDM2-SNP T309G and prostate cancer risk in overall analysis
      (GT/TT: OR = 0.84, 95%CI = 0.60-1.19; GG/TT: OR = 0.69, 95%CI = 0.43-1.11;
      dominant model: OR = 0.81, 95%CI= 0.58-1.13; recessive model: OR = 1.23, 95%CI =
      0.95-1.59). In subgroup analysis, the polymorphism seemed more likely to be a
      protective factor in Europeans (GG/TT: OR = 0.52, 95%CI = 0.31-0.87; recessive
      model: OR = 0.58, 95%CI = 0.36-0.95) than in Asian populations, and a protective
      effect of the polymorphism was also seen in hospital-based studies in all models
      (GT/TT: OR = 0.74, 95%CI = 0.57-0.97; GG/TT: OR = 0.55, 95%CI = 0.38-0.79;
      dominant model: OR = 0.69, 95%CI = 0.54-0.89; recessive model: OR = 0.70, 95%CI =
      0.51-0.97). However, more primary studies with a larger number of samples are
      required to confirm our findings.

PMID- 23167338
TI  - Markers of bone metastases in breast and lung cancers.
AB  - AIM AND BACKGROUND: The aim of the present study was to evaluate correlations
      between serum osteocalcin, osteoprotegerin and NTX (Cross-linked N-telopeptides
      of Type I Collagen) and urinary NTX in breast and lung cancer patients with bone
      metastases. These four markers are considered to have important roles in bone
      formation, resorption and metastases. METHODS: Four markers were determined in
      the sera of 60 breast cancer and 21 lung cancer patients and healthy controls
      (n=30). Serum levels were studied using ELISA and EIA. RESULTS: The median levels
      of serum osteoprotegerin (p<0.001) and osteocalcin (p=0.003) were higher in
      patients. Significant correlations were observed between the serum NTX
      osteocalcin (r=0.431; p<0.001), serum NTX- osteoprotegerin (r=0.42; p=0.003) and
      serum NTX - urine NTX (r=0.255; p=0.022). CONCLUSION: We conclude that
      osteocalcin, osteoprotegerin and NTX are independent diagnostic tools. Due to the
      ease of urine collection, urine NTX may be applied routinely to allow early
      detection of bone metastases and indicate progression of the disease.

PMID- 23167339
TI  - Sirolimus and non-melanoma skin cancer prevention after kidney transplantation: a
      meta-analysis.
AB  - BACKGROUND: Whether sirolimus is useful in the prevention of non-melanoma skin
      cancer (NMSC) remains unclear and we therefore performed this meta-analysis of
      randomized controlled trials to test the hypothesis that Sirolimus-based
      immunosuppression is associated with a decrease in NMSC. METHODS: The main
      outcomes were NMSC, squamous-cell carcinoma and basal-cell carcinoma. The pooled
      risk ratio (RR) with its 95% confidence interval (95%CI) were used to assess the
      effects. RESULTS: 5 randomized trials involving a total of 1499 patients
      receiving kidney transplantation were included. Patients undergoing Sirolimus
      based immunosuppression had much lower risk of NMSC (RR = 0.49, 95%CI 0.32-0.76,
      P = 0.001). Subgroup analyses by tumor type showed that Sirolimus-based
      immunosuppression significantly decreased risk of both squamous-cell carcinoma
      (RR = 0.58, 95%CI 0.43-0.78, P < 0.001) and basal-cell carcinoma (RR = 0.56,
      95%CI 0.37-0.85, P = 0.006). The quality of evidence was high for NMSC, and
      moderate for squamous-cell carcinoma and basal-cell carcinoma. No evidence of
      publication bias was observed. CONCLUSION: High quality evidence suggests that
      Sirolimus-based immunosuppression decreases risk of non-melanoma skin cancer, and
      Sirolimus has an antitumoral effect among kidney-transplant recipients.

PMID- 23167340
TI  - Reduced expression of LIMD1 in ulcerative oral epithelium associated with tobacco
      and areca nut.
AB  - PURPOSE: The aim of this study was to cast light on initiating molecular events
      associated with the development of premalignant oral lesions induced by tobacco
      and/or areca nut. METHOD: Immunohistochemical analyses of cell cycle regulatory
      proteins (LIMD1, RBSP3, p16, RB, phosphorylated RB, p53), EGFR and SH3GL2 (EGFR
      associated protein) were performed with inflammatory/ ulcerative epithelium and
      adjacent hyperplastic/mild dysplastic lesions. RESULTS: No change in expression
      of the proteins was seen in inflammatory epithelium. Reduced nuclear expression
      of LIMD1 was evident in ulcerative epithelium. In hyperplastic lesions, reduced
      expression of RBSP3, p16, SH3GL2 and overexpression of p-RB and EGFR were
      apparent. Reduced nuclear expression of p53 was observed in mild dysplastic
      lesions. CONCLUSION: Our data suggest that inactivation of LIMD1 in ulcerative
      epithelium might predispose the tissues to alterations of other cell cycle
      regulatory and EGFR signaling proteins needed for the development of premalignant
      oral lesions.

PMID- 23167341
TI  - Trends of breast cancer and its management in the last twenty years in Aden and
      adjacent governorates, Yemen.
AB  - BACKGROUND: Breast cancer is the most common cancer of women and the principal
      cause of death in middle aged women. The objective of this study was to describe
      the trend of breast cancer and its management in Aden and adjacent south-eastern
      governorates of Yemen during the last 20 years. PATIENTS AND METHODS: This is a
      retrospective analysis of previous studies on patients with breast cancer in Aden
      and adjacent south-eastern governorates, Yemen (January 1989 through December
      2007). The studied variables were: sex, age, time and type of presentation,
      disease stage, pathological types and the performed surgical treatment. The
      sources of information were the treatment registry of Aden health office,
      archives of Al-Gamhouria teaching hospital; major referral and other public and
      private hospitals in Aden and Aden Cancer Registry. RESULTS: The total number of
      patients was 476, 99% being females. The age range was 19-88 years. The most
      affected age was 30-50 years (60.5%), 95% presenting after one month of having
      breast symptoms. Forty-five percent presented with signs of advanced local
      disease, while 59.2% had palpable axillary lymph nodes on presentation. Early
      breast cancer (stages I-II) occurred in 47%, and late breast cancer (stages III
      IV) in 51.5%. Invasive ductal carcinoma was the commonest pathology (89.3%). The
      main surgical treatment was mastectomy (modified radical mastectomy (50%).
      CONCLUSION: Breast cancer is predominantly a disease of young with late
      presentation and advanced disease. Improving health awareness and earlier
      diagnosis of the disease by health education, encouraging breast self
      examination, and providing the mammography equipment and mammary clinics in
      hospitals are recommended. Establishment of oncology and radiotherapy centers in
      Aden is a necessity.

PMID- 23167342
TI  - Non-enzymatic antioxidant status and biochemical parameters in the consumers of
      Pan Masala containing tobacco.
AB  - BACKGROUND: Tobacco consumption is one of the leading causes of oral submucous
      fibrosis, oral cancer and even premature death. The present study was designed to
      compare the biochemical parameters and non- enzymatic antioxidant status and the
      lipid peroxidation products in pan masala tobacco users as compared with age
      matched non-user controls. METHODS: Pan masala and tobacco users of age 33.2+/
      9.94 years and age-matched controls (31.2+/-4.73 years) were enrolled for the
      study. Plasma levels of vitamin E, vitamin C, albumin, bilirubin, uric acid,
      glucose, urea, creatinine, aspartate amino transferase (AST), alanine amino
      transferase (ALT) were measured by standard methods. Serum malondialdehyde (MDA)
      levels were estimated as a measure of lipid peroxidation. RESULTS: In the pan
      masala tobacco users, as compared to the controls, the level of vitamin C (68.5+/
      5.9 vs 97.9+/-9.03 MUmol/L, p<=0.05) vitamin E (18.4+/-5.3 vs 97.9+/-9.03
      MUmol/L, p<=0.001), albumin (37.5+/-7.01 vs 44.3+/-9.99 g/L, p<=0.001), and
      malondialdehyde (10.8+/-1.29 vs 1.72+/-1.15 nmol/ml, p<=0.001 ) were found to be
      significantly altered. Malondialdehyde was significantly correlated with vitamin
      E (r=1.00, p<0.001) and vitamin C (r =1.00, p<0.001) in pan masala tobacco users.
      Serum levels of AST (31.0+/-16.77 IU) and ALT (36.7+/-31.3 IU) in the pan masala
      tobacco users were significantly raised as compared to the controls (AST, 25.2+/
      9.51 IU, p=0.038; ALT, 26.2+/-17.9 IU, p=0.038). CONCLUSION: These findings
      suggest that pan masala tobacco users are in a state of oxidative stress
      promoting cellular damage. Non-enzymatic antioxidants are depleted in pan masala
      tobacco users with subsequent alteration in the biochemical parameters.
      Supplementation of antioxidants may prevent oxidative damage in pan masala
      tobacco users.

PMID- 23167343
TI  - Are there time-period-related differences in the prophylactic effects of Bacille
      Calmette-Guerin intravesical instillation therapy in Japan?
AB  - OBJECTIVE: The guidelines on indications for prophylactic use of Bacille Calmette
      Guerin (BCG) against non- muscle-invasive bladder cancer (NMIBC) have changed
      over the years. In order to assess the impact on outcome, the present
      retrospective comparison of BCG efficacy by time period with Japanese patients
      was conducted. PATIENTS AND METHODS: A total of 146 cases of NMIBC treated with
      BCG since February 1985 were retrospectively evaluated. All patients received 80
      mg of BCG (Tokyo 172 strain) six to eight times a week for prophylactic use.
      Comparison was made among three historical groups (Group A: 1980's, 39 cases;
      Group B: 1990's, 61 cases; Group C: 2000's, 46 cases). RESULTS: In total,
      recurrence was seen in 55 of the 146 cases (37.7%), and progression in 14 (9.6%),
      1 patient dying of cancer. These overall results were similar to those outlined
      in previous reports. However, the outcomes of this time-period-based analysis
      indicated a tendency for a shorter time to recurrence in patients after 2000,
      although a log-rank test showed no significance (P=0.229). Seven of the cases
      featuring progression (i.e., half of all such cases) were among the 46 Group C
      patients (15.2%). Excluding these progressive cases, there was no significant
      difference among the remaining 132 patients in the three groups. CONCLUSION: This
      study results revealed a tendency for a lower non-recurrence rate after 2000 in
      our series. This could stem from a number of factors, including changes in BCG
      indication criteria and the evolution of histopathological diagnostic criteria.

PMID- 23167344
TI  - Up-regulation of NICE-3 as a novel EDC gene could contribute to human
      hepatocellular carcinoma.
AB  - The epidermal differentiation complex (EDC) contains a large number of gene
      products which are crucial for the maturation of the human epidermis and can
      contribute to skin diseases, even carcinogenesis. It is generally acepted that
      activation of oncogenes and/or inactivation of tumor suppressor genes play
      pivotal roles in the process of carcinogenesis. Here, NICE-3, a novel EDC gene,
      was found to be up-regulated in human hepatocellular carcinoma (HCC) by
      quantitative real-time RT-PCR. Furthermore, overexpression of exogenous NICE-3 by
      recombinant plasmids could significantly promote cell proliferation, colony
      formation and soft agar colony formation in Focus and WRL-68 HCC cell lines.
      Reversely, NICE-3 silencing by RNA interference could markedly inhibit these
      malignant phenotypes in YY-8103 and MHCC-97H cells. Moreover, cell cycle analysis
      of MHCC-97H transfected with siRNA by flow cytometry showed that NICE-3 knockdown
      may inhibit cell growth via arrest in G0/G1 phase and hindering entry of cells
      into S phase. All data of our findings indicate that NICE-3 may contribute to
      human hepatocellular carcinoma by promoting cell proliferation.

PMID- 23167345
TI  - Metastatic bone disease as seen in our clinical practice--experience at a
      tertiary care cancer center in Pakistan.
AB  - AIM: Metastatic tumor of bone is the most common malignancy involving bone and is
      an important predictor of prognosis in advanced cancers. The prognosis depends
      upon the primary site of origin and the extent of disease. In current study, we
      present the pattern and distribution of metastatic bone disease seen in the
      leading cancer care center of Pakistan, Shaukat Khanum Cancer Hospital and
      Research Center (SKMCH and RC), Lahore. MATERIALS AND METHODS: All cases of bony
      metastatic disease were included that presented in the Pathology Department ,
      from Jan 2005 to July 2011. Patients of all ages and both sexes were included.
      Primary bone tumors, lymphomas, sarcomas and other malignancies were excluded.
      The data were recorded and analyzed with SPSS 16.0. RESULTS: A total of 146 cases
      of metastatic bone disease were included in the study. Out of the total cases, 79
      were male and 67 were female. Age range 25-82 years (median 52). Hip bone was the
      most frequent bone involved, with femur and vertebrae as second and third in the
      list. The commonest bone involved in males was vertebrae with 23 cases and in
      females was hip bone with 22 cases. Regarding primary site, cancers of breast,
      prostate and gastrointestinal tract were at the top of the list with prostate and
      breast being the most frequent primary sites of metastasis in males and females
      respectively. CONCLUSION: Bone metastasis is an important entity to consider in
      the differential diagnosis whenever a bony tumor especially carcinoma present in
      older age. Our data are comparable with international findings and the literature
      available regarding the site and distribution of skeletal metastatic lesions. A
      slight deviation noted was more common bony metastatic lesions with ovarian
      primaries in females and gastrointestinal tract cancers in males in our study.

PMID- 23167347
TI  - Comparison different methods of intraoperative and intraperitoneal chemotherapy
      for patients with gastric cancer: a meta-analysis.
AB  - PURPOSE: To investigate the efficacy and safety of intraperitoneal chemotherapy
      (IPC) for patients with gastric cancer and to compare effects between different
      regimens of IPC. METHOD: Randomized controlled trials comparing the effects of
      surgery plus intraperitoneal chemotherapy with surgery alone or comparing the
      efficacy between different regimens of intraperitoneal chemotherapy were searched
      for in Medline, Embase, Pubmed, the Cochrane Library and the Chinese BioMedical
      Disc and so on by two independent reviewers. After quality assessment and data
      extraction, data were pooled for meta-analysis using RevMan5.16 software. Tests
      of interaction were used to test for differences of effects among subgroups
      grouped according to different IPC regimens. RESULTS: Fifteen RCTs with a total
      of 1713 patients with gastric cancer were included for quality assessment and
      data extraction. Ten studies were judged to be of fair quality and entered into
      meta-analysis. Hyperthermic intraoperative intraperitoneal chemotherapy (HR=0.60,
      P<0.01), hyperthermic intraoperative intraperitoneal chemotherapy plus
      postoperative intraperitoneal chemotherapy (HR=0.47, P<0.01) and normothermic
      intraoperative intraperitoneal chemotherapy (HR=0.70, P=0.01) were associated
      with a significant improvement in overall survival. Tests of interaction showed
      that hyperthermia and additional postoperative intraperitoneal chemotherapy did
      not impact on its effect. Further analysis revealed that intraperitoneal
      chemotherapy remarkably decrease the rate of postoperative hepatic metastasis by
      73% (OR=0.27, 95% CI=0.12 to 0.67, P<0.01). However, intraperitoneal chemotherapy
      increased risks of marrow depression (OR=5.74, P<0.01), fever (OR=3.67, P=0.02)
      and intra-abdominal abscess (OR=3.57, P<0.01). CONCLUSION: The present meta
      analysis demonstrates that hyperthermic intraoperative intraperitoneal
      chemotherapy and normothermic intraoperative intraperitoneal chemotherapy should
      be recommended to treat patients with gastric cancer because of improvement in
      overall survival. However, it is noteworthy that intraperitoneal chemotherapy can
      increase the risks of marrow depression, intra-abdominal abscesses, and fever.

PMID- 23167346
TI  - Impact of chemotherapy on hypercalcemia in breast and lung cancer patients.
AB  - INTRODUCTION: Hypercalcemia is mainly caused by bone resorption due to either
      secretion of cytokines including parathyroid hormone-related protein (PTHrP) or
      bone metastases. However, hypercalcemia may occur in patients with or without
      bone metastases. The present study aimed to describe the effect of chemotherapy
      treatment, regimens and doses on calcium levels among breast and lung cancer
      patients with hypercalcemia. METHODS: We carried a review of medical records of
      breast and lung cancer patients hospitalized in years 2003 and 2009 at Penang
      General Hospital, a public tertiary care center in Penang Island, north of
      Malaysia. Patients with hypercalcemia (defined as a calcium level above 10.5
      mg/dl) at the time of cancer diagnosis or during cancer treatment had their
      medical history abstracted, including presence of metastasis, chemotherapy types
      and doses, calcium levels throughout cancer treatment, and other co-morbidity.
      The mean calcium levels at first hospitalization before chemotherapy were
      compared with calcium levels at the end of or at the latest chemotherapy
      treatment. Statistical analysis was conducted using the Chi-square test for
      categorical data, logistic regression test for categorical variables, and
      Spearman correlation test, linear regression and the paired sample t tests for
      continuous data. RESULTS: Of a total 1,023 of breast cancer and 814 lung cancer
      patients identified, 292 had hypercalcemia at first hospitalization or during
      cancer treatment (174 breast and 118 lung cancer patients). About a quarter of
      these patients had advanced stage cancers: 26.4% had mild hypercalcemia (10.5
      11.9 mg/dl), 55.5% had moderate (12-12.9 mg/dl), and 18.2% severe hypercalcemia
      (13-13.9; 14-16 mg/dl). Chemotherapy lowered calcium levels significantly both in
      breast and lung cancer patients with hypercalcemia; in particular with
      chemotherapy type 5-flurouracil+epirubicin+cyclophosphamide (FEC) for breast
      cancer, and gemcitabine+cisplatin in lung cancer. CONCLUSION: Chemotherapy
      decreases calcium levels in breast and lung cancer cases with hypercalcemia at
      cancer diagnosis, probably by reducing PTHrP levels.

PMID- 23167348
TI  - Survival of patients with lung cancer, Yazd, Iran.
AB  - BACKGROUND: Lung carcinoma is the leading cause of cancer mortality worldwide.
      Although the 5-year survival rate nearly tripled from 5-15% over the last 25
      years, the estimated number of deaths still exceeds 1.3 million annually. The
      overall 5-year survival of lung cancer is only 10% in Europe and 15% in the
      United States. The aim of the current study was to determine the long-term
      survival and the effect of certain prognostic factors on survival of patients
      with lung cancer in Yazd city, Iran. METHODS: In this cross-sectional descriptive
      study, we retrospectively reviewed hospital records and follow-up data of 148
      patients with histological proven lung cancer using the cancer data registered
      between 1998 and 2005 in the pathology department of Shahid Sadoughi educational
      hospital, Yazd, Iran. Data were extracted from patient documents that included
      sex, age, clinical manifestations, histopathological report of the tumor and type
      of treatment given. RESULTS: Overall survival time in all patients was 8.5 months
      after diagnosis and there was no significant difference in survival according to
      sex (p=0.958). Histological analysis revealed that squamous cell carcinoma was
      the most common histologic type (35%). Kaplan-Meier statistical methods estimated
      the average survival time for SCC to be better (22.6 months) in comparison with
      the other types of histology (all of them below 10 months). There was a trend
      towards significance between type of histology and duration of survival (p=0.08).
      CONCLUSION: It is reasonable to expect that early lung cancer detection, and
      appropriated treatment, may improve surgical morbidity and mortality. Low
      survival of lung cancer in our center patients show our shortages in screening
      programs for early diagnosis. Designing studies with larger sample size that take
      some other variables like staging of patients is now necessary.

PMID- 23167349
TI  - Amelioration of 1,2 Dimethylhydrazine (DMH) induced colon oxidative stress,
      inflammation and tumor promotion response by tannic acid in Wistar rats.
AB  - Colon cancer is the third most common malignant neoplasm in the world and it
      remains an important cause of death, especially in western countries. The toxic
      environmental pollutant, 1, 2-dimethylhydrazine (DMH), is also a colon-specific
      carcinogen. Tannic acid (TA) is reported to be effective against various types of
      chemically induced toxicity and also carcinogenesis. In the present study, we
      evaluated the chemopreventive efficacy of TA against DMH induced colon toxicity
      in a rat model. Efficacy of TA against the colon toxicity was evaluated in terms
      of biochemical estimation of antioxidant enzyme activities, lipid peroxidation,
      histopathological changes and expression of early molecular markers of
      inflammation and tumor promotion. DMH treatment induced oxidative stress enzymes
      (p<0.001) and an early inflammatory and tumor promotion response in the colons of
      Wistar rats. TA treatment prevented deteriorative effects induced by DMH through
      a protective mechanism that involved reduction of oxidative stress as well as COX
      2, i-NOS, PCNA protein expression levels and TNF-alpha(p<0.001) release. It could
      be concluded from our results that TA markedly protects against chemically
      induced colon toxicity and acts plausibly by virtue of its antioxidant, anti
      inflammatory and antiproliferative activities.

PMID- 23167350
TI  - Glutathione-S-transferase T1 polymorphism is associated with esophageal cancer
      risk in Chinese Han population.
AB  - BACKGROUND: Glutathione-S-Transferase T1 (GSTT1) gene has been shown to be
      involved in the development of esophageal cancer. However, the results have been
      inconsistent. In this study, the authors performed a meta- analysis to clarify
      the association between GSTT1 polymorphism and esophageal cancer risk among
      Chinese Han population. METHODS: Published literature from PubMed, the China
      National Knowledge Infrastructure and Wanfang Data were searched. Pooled odds
      ratio (OR) and 95% confidence interval (95%CI) was calculated using a fixed- or
      random-effects model. RESULTS: Eleven studies with a total of 2779 individuals
      were included in the meta-analysis. The results showed that GSTT1 null genotype
      was significantly associated with esophageal cancer risk in Chinese (OR = 1.31,
      95%CI 1.12 to 1.53, p = 0.001). Further sensitivity analyses confirmed the
      significant association. The cumulative meta-analysis showed a trend of an
      obvious association between GSTT1 null genotype and esophageal cancer risk as
      information accumulated by year. CONCLUSIONS: This meta-analysis suggests a
      significant association of GSTT1 null genotype with esophageal cancer risk in the
      Chinese Han population.

PMID- 23167351
TI  - Estimation of superoxide dismutase and glutathione peroxidase in oral submucous
      fibrosis, oral leukoplakia and oral cancer--a comparative study.
AB  - Present study was undertaken to estimate and compare erythrocyte superoxide
      dismutase (E-SOD) and Glutathione peroxidase (GPx) levels in oral submucous
      fibrosis, oral leukoplakia and oral cancer patients and age/sex matched healthy
      subjects, 25 in each group. Statistically significant (P<0.001) decrease in E-SOD
      and GPx levels were observed in OSF, oral leukoplakia and oral cancer groups as
      compared to the control group. Oral leukoplakia group showed lower levels in
      comparison with OSF (P>0.05). Oral cancer group had the lowest levels amongst the
      study groups. Imbalance in antioxidant enzyme status may be considered as one of
      the factors responsible for the pathogenesis of cancer and may serve as a
      potential biomarker and therapeutic target to reduce the malignant transformation
      in oral premalignant lesions/conditions.

PMID- 23167352
TI  - Prognostic significance of GSTP1, XRCC1 and XRCC3 polymorphisms in non-small cell
      lung cancer patients.
AB  - AIM: Individual differences in chemosensitivity and clinical outcome in non-small
      cell lung cancer (NSCLC) patients treatment with platinum-based chemotherapy may
      be due to genetic factors. Our study aimed to investigate the prognostic role of
      GSTP1, XRCC1 and XRCC3 in NSCLC patients treated with chemotherapy. METHODS: A
      total of 460 cases were consecutively selected from The Affiliated Hospital of
      Nantong University between Jan. 2003 to Nov. 2006, and all were followed-up until
      Nov. 2011. Genotyping of GSTP1 Ile105Val, XRCC1 Arg194Trp, XRCC1 Arg399Gln and
      XRCC3 Thr241Met was conducted by duplex polymerase-chain-reaction with
      confronting-two-pair primer methods. RESULTS: Patients with GSTP Val/Val
      exhibited a shorter survival time, and had a 1.89 fold greater risk of death than
      did those with the IIe/IIe genotype. For XRCC1 Arg194Trp, the variant genotype
      Trp/Trp was significantly associated with a decreased risk of death from NSCLC
      when compared with the Arg/Arg. Individuals carrying XRCC1 399Gln/Gln genotype
      had a longer survival time, with a lowered risk of death from NSCLC. CONCLUSION:
      This study indicated that GSTP1 Ile105Val, XRCC1 Arg194Trp and XRCC1Arg399Gln
      genes have a role in modifying the effect of platinum-based chemotherapy for
      NSCLC patients in a Chinese population. Our findings provide information for
      therapeutic decisions for individualized therapy in NSCLC cases.

PMID- 23167353
TI  - Relationship between GSTT1 gene polymorphism and hepatocellular carcinoma in
      patients from China.
AB  - OBJECTIVE: The results from studies on associations of the glutathione S
      transferase T1 (GSTT1) gene polymorphism and hepatocellular carcinoma (HCC) risk
      in Chinese populations are still conflicting. This meta- analysis was performed
      to evaluate the relationship in detail. METHODS: Eligible reports were recruited
      into this meta-analysis from the databases of PubMed, Embase, Cochrane Library
      and CBM-disc (China Biological Medicine Database). Results were expressed with
      odds ratios (OR) for dichotomous data, and 95% confidence intervals (CI) were
      also calculated. RESULTS: Eighteen investigations were identified for the
      analysis of association between polymorphic deletion of GSTT1 and HCC, consisting
      of 2,693 patients with HCC and 4,696 controls. Null genotype of GSTT1 was
      associated with HCC susceptibility in Chinese (OR=1.53, 95%CI: 1.28-1.82;
      P<0.00001). CONCLUSION: The GSTT1 null genotype is associated with HCC
      susceptibility in Chinese.

PMID- 23167354
TI  - Association of XPD and XRCC1 genetic polymorphisms with hepatocellular carcinoma
      risk.
AB  - AIM: XRCC1 and XPD are two major repair genes involved in nucleotide excision
      repair (NER), which is reported to be associated with risk of several cancers. We
      explored the association of XRCC1 and XPD polymorphisms with the risk of HCC.
      METHODS: A total of 410 cases with HCC and 410 health controls were collected.
      XRCC1 Arg194Trp, XRCC1 Arg399Gln, XPD Lys751Gln and XPD Asp312Asn genotyping was
      performed by duplex polymerase-chain-reaction with the confronting-two-pair
      primer (PCR-CTPP) method. RESULTS: XRCC1 194Trp/Trp was strongly significantly
      associated with an increased risk of HCC cancer when compared with the wide-type
      genotype (OR=2.26, 95% CI=(1.23-5.38). Individuals carrying the XRCC1 399Gln/ Gln
      showed increased risk of HCC (OR=1.74, 95%CI=1.06-2.74). The XPD 751Gln/Gln and
      Gln allele genotype were associated with strong elevated susceptibility to HCC
      (OR=3.51 and 1.42, respectively). CONCLUSION: These results suggest that
      polymorphisms in XRCC1 and XPD may have functional significance in risk of HCC.

PMID- 23167355
TI  - Knowledge, perception, practice and barriers of breast cancer health promotion
      activities among community pharmacists in two Districts of Selangor state,
      Malaysia.
AB  - Breast cancer is the most common cancer and the leading cause of cancer death
      among women in Malaysia. Despite the campaigns undertaken to raise the awareness
      of the public regarding breast cancer, breast cancer screening rates are still
      low in the country. The community pharmacist, as one of the most accessible
      healthcare practitioners, could play a role in the provision of breast cancer
      health promotion services to the community. However, there are no documented data
      regarding the community pharmacists' involvement in breast cancer related health
      promotion activities. Hence, this study was conducted to examine self-reported
      knowledge, practice and perception of community pharmacists on provision of
      breast cancer health promotion services and to investigate the barriers that
      limit their involvement. This cross-sectional survey conducted between May to
      September 2010, included a sample of 35 community pharmacists working in the
      districts of Hulu Langat and Sepang in state of Selangor. A 22-item validated
      questionnaire that included both closed and Lickert scale questions was used to
      interview those pharmacists who gave their informed consent to participate in the
      study. The data was analysed using SPSS. Only 11.3% of the community pharmacists
      answered all the questions on the knowledge section correctly. The mean overall
      knowledge of the community pharmacists on risk factors of breast cancer and
      screening recommendations is 56%. None of the respondents was currently involved
      in breast cancer health promotion activities. Lack of time (80%), lack of breast
      cancer educational materials (77.1%) and lack of training (62.9%) were the top
      three mentioned barriers. Despite these barriers, 94.3% (33) of the community
      pharmacists agreed that they should be involved in breast cancer health promotion
      activities. Hence, there is need to equip community pharmacists with necessary
      training and knowledge to enable them to contribute their share towards
      prevention and screening of breast cancer.

PMID- 23167356
TI  - Nature of lesions undergoing radical nephrectomy for renal cancer.
AB  - AIM: The aim of the present study was to evaluate retrospectively
      histopathologically-diagnosed lesions that were detected in the kidney after
      radical nephrectomy for a preoperative diagnosis of kidney cancer. METHODS: The
      medical records of 83 patients (51 male, 32 female) were included. Preoperative
      staging was accomplished by various methods including physical examination, blood
      hemography and biochemistry, abdominal ultrasonography (US), chest x-ray,
      abdominal computed tomography (CT) and abdominal magnetic resonance imaging
      (MRI). RESULTS: Totals of 70 patients underwent radical nephrectomy and 13
      nephron sparing surgery. Of the 83 patients, 70 had malignant lesions (renal cell
      carcinoma, squamous cell carcinoma or other malignancies) 13 had a variety of
      benign lesions, the most frequently detected being oncoytoma (6), angiomyolipoma
      (3), xanthogranulamatous pyelonephritis (2), cortical cyst (1) and chronic
      pyelonephritic change (1). CONCLUSION: It was concluded that in spite of great
      technological developments regarding radiological imaging modalities such as US,
      CT and MRI, benign lesions might still be detected pathologically in patients who
      undergo radical nephrectomy with the preoperative diagnosis of renal cancer. But,
      all renal masses should be regarded as malignant and should be managed surgically
      otherwise proven benign.

PMID- 23167357
TI  - Silencing of twist expression by RNA interference suppresses epithelial
      mesenchymal transition, invasion, and metastasis of ovarian cancer.
AB  - PURPOSE: This study aimed to explore the role of the Twist gene in the epithelial
      mesenchymal transition of ovarian cancer. METHODS: An RNA interference plasmid
      expressing a small interfering RNA (siRNA)-targeting Twist (Twist siRNA vector)
      was designed, constructed, and transfected into the human ovarian cancer cell
      line A2780. Transfection efficiency was assessed under a fluorescence microscope.
      Changes in the expression of Twist mRNA in A2780 after transfection with the
      pGenesil Twist shRNA plasmid were analyzed through RT-PCR. MTT assays and
      adhesion experiments were applied to determine changes in proliferation and
      adhesion ability of A2870 after transfection with the Twist shRNA plasmid.
      Changes in the expression of the E-cadherin and N-cadherin proteins in A2780
      after transfection with the Twist shRNA plasmid were analyzed using Western
      blotting. RESULT: The restructuring plasmid pGenesil-Twist shRNA was constructed
      successfully. After 48 h of culture, 80% of the cells expressed high-intensity
      GFP fluorescence and stability. The expression of Twist decreased significantly
      after the transfection of the Twist shRNA plasmid (P<0.05). Proliferation of the
      transfected Twist shRNA cells showed no difference with that of the A2780
      nontransfection or A2780-si-control groups (P>0.05) but the adhesion ability of
      A2780 decreased dramatically (P<0.05). Expression of the E-cadherin protein
      increased, whereas that of the N-cadherin protein decreased compared with that in
      the A2780-nontransfection or A2780- si-control groups (P<0.05). CONCLUSION: Twist
      is essential for epithelial-mesenchymal transition, invasion, and metastasis of
      ovarian cancer.

PMID- 23167358
TI  - Meta-analysis of the relation between the VDR gene TaqIpolymorphism and genetic
      susceptibility to prostate cancer in Asian populations.
AB  - BACKGROUND: Polymorphisms of the Taq I gene have been associated with prostate
      cancer risk. METHODS: We applied a fixed-effects model to combine odds ratios
      (ORs) and 95% confidence intervals (95% CI). The Egger's test was carried out to
      evaluate potential publication bias. RESULTS: A total of 10 case-control studies
      enrolling 1,141 prostate cancer patients and 1,685 controls were included in this
      meta-analysis. Compared with the T allele, the OR for the C allele was 0.81 (0.70
      0.94). The ORs for CT and CC+CT genotypes were 0.86 (0.74-1.01) and 0.84 (0.73
      0.97) compared to wide type genotype (homozygote TT). CONCLUSIONS: The present
      meta-analysis suggests that the TF gene Taq I polymorphism may reduce the
      prostate cancer risk in Asian populations.

PMID- 23167359
TI  - Characteristics of invasive breast ductal carcinoma, NOS, diagnosed in a tertiary
      institution in the East Coast of Malaysia with a focus on tumor angiogenesis.
AB  - BACKGROUND: Prognosis of breast cancer depends on classic pathological factors
      and also tumor angiogenesis. This study aimed to evaluate the clinicopathological
      factors of breast cancer in a tertiary centre with a focus on the relationship
      between tumor angiogenesis and clinicopathological factors. METHODS:
      Clinicopathological data were retrieved from the archived formal pathology
      reports for surgical specimens diagnosed as invasive ductal carcinoma, NOS.
      Microvessels were immunohistochemically stained with anti-CD34 antibody and
      quantified as microvessel density. RESULTS: At least 50% of 94 cases of invasive
      breast ductal carcinoma in the study were advanced stage. The majority had poor
      prognosis factors such as tumor size larger than 50mm (48.9%), positive lymph
      node metastasis (60.6%), and tumor grade III (52.1%). Higher percentages of
      estrogen and progesterone receptor negative cases were recorded (46.8% and 46.8%
      respectively). Her-2 overexpression cases and triple negative breast cancers
      constituted 24.5% and 22.3% respectively. Significantly higher microvessel
      density was observed in the younger patient age group (p=0.012). There were no
      significant associations between microvessel density and other
      clinicopathological factors (p>0.05). CONCLUSIONS: Majority of the breast cancer
      patients of this institution had advanced stage disease with poorer prognostic
      factors as compared to other local and western studies. Breast cancer in younger
      patients might be more proangiogenic.

PMID- 23167361
TI  - Do Saudi nurses in primary health care centres have breast cancer knowledge to
      promote breast cancer awareness?
AB  - BACKGROUND: Breast cancer is one of the leading causes of death among cancer
      patients in Saudi Arabia. It is known that nurses play a key role in promoting
      breast cancer awareness among women in any society. Nurses in primary health care
      centres (PHCC) have more direct contact with general population. This study aimed
      to investigate nurse knowledge of breast cancer and practice of early screening
      in PHCC in Jeddah city. METHODS: A cross-sectional study was conducted using a
      self-administered questionnaire to assess the general knowledge of breast cancer,
      risk factors, and practice of 210 PHCC nurses. Data were analysed using SPSS
      v.16. RESULTS: The mean age of the PHCC Nurses was 36.9 (SD +/-8.6). Only 11%
      percent scored <50% of the total score for general epidemiological knowledge on
      breast cancer, about 35% scored <50% of the total score for breast cancer risk
      factors. Sixty seven percent scored >75% of the total score on breast cancer
      signs. Majority of nurses 62.8% practiced BSE, but only 4% practiced regularly
      every month. Some 28% practiced once per year. About 81% of the nurses had not
      had a clinical breast examination and only 14% had had a mammography. The results
      of the study failed to show any correlation between the knowledge scores with
      age, education, year of experience, family history of BC and marital status of
      the nurses. CONCLUSION: The results from the study reflect that there is a need
      to provide continuing nursing education programmes for PHCC nurses to improve
      their breast cancer knowledge and practice.

PMID- 23167360
TI  - Tanshinone II--a inhibits angiogenesis through down regulation of COX-2 in human
      colorectal cancer.
AB  - Angiogenesis plays a significant role in colorectal cancer (CRC) and
      cyclooxygenase-2 (COX-2) appears to be involved with multiple aspects of CRC
      angiogenesis. Our aim was to investigate the inhibitory effects of Tan II-A
      (Tanshinone II-A, Tan II-A) on tumor growth in mice, as well as alteration of
      expression of COX-2 and VEGF in CRC. We established the mice xenograft model of
      C26 CRC cell line, and injected 0.5, 1, 2mg/kg of Tan II-A and 1mg/kg of 5-FU in
      respectively in vivo. Then, we assayed tumor weight and volume, and evaluated
      microvascular density and expression of VEGF. COX-2 promoter and COX-2 plasmids
      were transfected into HCT-116 cells, followed by detection of COX-2 promoter
      activity by chemiluminescence, and detection of COX-2 mRNA expression by
      fluorescence quantitative PCR. Taken together, the results showed Tan II-A could
      inhibit tumor growth and suppress the VEGF level in vivo. HCT-116 cell
      experiments showed marked inhibitory effects of Tan II-A on COX-2 and VEGF in a
      dose-dependent manner. The results indicate that Tan II-A can effectively inhibit
      tumor growth and angiogenesis of human colorectal cancer via inhibiting the
      expression level of COX-2 and VEGF.

PMID- 23167362
TI  - Lack of association of glutathione S-transferase M3 gene polymorphism with the
      susceptibility of lung cancer.
AB  - OBJECTIVE: The conclusions of published reports on the relationship between the
      glutathione S-transferase M3 (GSTM3) A/B gene polymorphism and the risk of lung
      cancer are still debated. This meta-analysis was performed to evaluate the
      association between GSTM3 and the risk of lung cancer. METHODS: Association
      investigations were identified from PubMed, Embase, and Cochrane Library, and
      eligible studies were included and synthesized using a meta-analysis method.
      RESULTS: Eight reports were included into this meta-analysis for the association
      of GSTM3 A/B gene polymorphism and lung cancer susceptibility, covering 1,854
      patients with lung cancer and 1,926 controls. No association between the GSTM3
      A/B gene polymorphism and lung cancer was found in this meta-analysis (B allele:
      OR = 1.25, 95% CI: 0.89-1.76, P = 0.20; BB genotype: OR = 1.53, 95% CI: 0.71
      3.32, P = 0.28; AA genotype: OR = 0.85, 95% CI: 0.59-1.23, P = 0.39).
      CONCLUSIONS: The GSTM3 A/B gene polymorphism is not associated with lung cancer
      susceptibility. However, more studies on the relationship between GSTM3 A/B gene
      polymorphism and the risk of lung cancer should be performed in the future.

PMID- 23167363
TI  - LINE-1 and Alu methylation patterns in lymph node metastases of head and neck
      cancers.
AB  - BACKGROUND: The potential use of hypomethylation of Long INterspersed Element 1
      (LINE-1) and Alu elements (Alu) as a biomarker has been comprehensively assessed
      in several cancers, including head and neck squamous cell carcinoma (HNSCC).
      Failure to detect occult metastatic head and neck tumors on radical neck lymph
      node dissection can affect the therapeutic measures taken. OBJECTIVE: The aim of
      this study was to investigate the LINE-1 and Alu methylation status and determine
      whether it can be applied for detection of occult metastatic tumors in HNSCC
      cases. METHODS: We used the Combine Bisulfite Restriction Analysis (COBRA)
      technique to analyse LINE-1 and Alu methylation status. In addition to the
      methylation level, LINE-1 and Alu loci were classified based on the methylation
      statuses of two CpG dinucleotides in each allele as follows: hypermethylation
      (mCmC), hypomethylation (uCuC), and 2 forms of partial methylation (mCuC and
      uCmC). Sixty-one lymph nodes were divided into 3 groups: 1) non-metastatic head
      and neck cancer (NM), 2) histologically negative for tumor cells of cases with
      metastatic head and neck cancer (LN), and 3) histologically positive for tumor
      cells (LP). RESULTS: Alu methylation change was not significant. However, LINE-1
      methylation of both LN and LP was altered, as demonstrated by the lower LINE-1
      methylation levels (p<0.001), higher percentage of mCuC (p<0.01), lower
      percentage of uCmC (p<0.001) and higher percentage of uCuC (p<0.001). Using
      receiver operating characteristic (ROC) curve analysis, %uCmC and %mCuC values
      revealed a high level of AUC at 0.806 and 0.716, respectively, in distinguishing
      LN from NM. CONCLUSION: The LINE-1 methylation changes in LN have the same
      pattern as that in LP. This epigenomic change may be due to the presence of
      occult metastatic tumor in LN cases.

PMID- 23167364
TI  - Absence of p53 gene mutations in exons 5 - 7 among breast cancer patients of
      Bengalee Hindu caste females, West Bengal, India.
AB  - BACKGROUND: The high incidence and relatively good prognosis of breast cancer has
      made it the most prevalent cancer in the world today. A large number of distinct
      mutations and polymorphisms in the p53 gene have been reported worldwide, but
      there is no report regarding the role of this inherited susceptibility gene in
      breast cancer risk among the Bengalee Hindu Caste females of West Bengal, India.
      AIM OF THE STUDY: We investigated the distribution and the nature of p53 gene
      mutations and polymorphisms in exons 5-7 in a cohort of 110 Bengalee Hindu breast
      cancer patients and 127 age, sex and caste matched controls by direct sequencing.
      RESULTS: We did not observe any mutations and polymorphisms in our studied
      individuals. CONCLUSION: We therefore conclude that mutations in exons 5-7 of p53
      gene are rare causes of breast cancer among Bengalee Hindu caste females, and
      therefore of little help for genetic counseling and diagnostic purposes.

PMID- 23167365
TI  - Association of chemotherapy-induced leucopenia with treatment outcomes in
      advanced non-small-cell lung cancer cases receiving the NP regimen.
AB  - BACKGROUND: Chemotherapy induced leutropenia has been shown to be associated with
      improved treatment outcomes in selected solid tumors. We studied the association
      of chemotherapy induced leutropenia with treatment related outcomes in advanced
      non-small-cell lung cancer. METHODS: This is a prospective analysis of patients
      receiving chemotherapy for advanced NSCLC at the Shandong Cancer Hospital from
      2005-07.The chemotherapy included cisplatin 35 mg/m2, IV on d1,2 and vinorelbine
      25 mg/m2 IV on d1,8 every 21 days. Patients were stratified into three groups (A)
      those experiencing grades 0 leucopenia, group (B) grades 1-2 and group (C) grades
      3-4. The outcomes studied were response rate (RR), disease control rate (DCR),
      and time to progression (TTP). RESULTS: 128 patients were studied. The RRs in
      groups A, B and C were 30.8%, 56.8% and 71.4%, respectively, p=0.010. The DCRs
      were 61.5%, 83.8% and 92.9%, respectively, p=0.009 and the median TTPs were 150
      days (95%CI: 91-209), 189 days (95%CI: 181-197) and 207 days (95%CI: 172-242),
      p=0.009. The differences in RR and TTP were significant. In patients whose CIL
      kept on 10 days at least, the TTP was significantly prolonged, p=0.0213, and the
      same was the case for those experiencing grades 1-2 leucopenia and ECOG 0,
      p=0.0412. CONCLUSIONS: Occurrence of CIL correlated with RR and TTP in patients
      with advanced NSCLC receiving cisplatin and vinorelbine chemotherapy, especially
      in patients experiencing grades 1-2 leucopenia and ECOG 0, and the same for those
      with CIL persisting for 10 days at least. CIL could be a biological measure of
      drug activity and a marker of efficacy.

PMID- 23167366
TI  - Anal cancer screening by modified liquid-based cytology in an HIV clinic.
AB  - This study aimed to screen for anal cancer and to determine its cytomorphology
      using liquid-based cytology (LBC) with specimens preserved in 95% ethyl alcohol.
      Anal swabs were collected for cytological examination from 177 adult, HIV
      infected patients. After collection, sample slides were reviewed and classified
      according to their cytomorphology using the modified Bethesda 2001 system. An
      abnormal anal Pap smear was found in 26.0% of the patients. The diagnoses were:
      66.7% negative for intraepithelial lesions (NIL), 14.1% with atypical squamous
      cells of undetermined significance (ASC-US), 10.7% (19) with low-grade squamous
      intraepithelial lesions (LSIL), and 1.13% with high-grade squamous
      intraepithelial lesions (HSIL). The cytological evaluation was an unsatisfactory
      result only with 6.67%. The present modified LBC using 95% ethyl alcohol as the
      preservative could thus be used for anal cancer screening. The number of SILs in
      Thai HIV-infected patients is lower than that in Western countries. We found anal
      cytology a satisfactory tool for early screening and detection of anal dysplasia
      commonly found in high-risk, HIV-infected patients.

PMID- 23167367
TI  - Determination of information and support needs of first degree relatives of women
      with breast cancer.
AB  - BACKGROUND: Breast cancer is the most frequent type of cancer among women in the
      world and the most common cause of deaths from cancer in females. In Turkey,
      breast cancer comes first in the list of the most frequent ten cancer types seen
      in women. As the incidence rate of breast cancer is high, many women having
      breast cancer in the family experience the breast cancer at secondhand. This
      study was carried out in an attempt to determine the information and support
      needs of women whose first-degree relatives have breast cancer and to what extent
      these needs are met. METHODS: The research sample consisted of 156 women.
      Questionnaire Form and Information and Support Needs Questionnaires were used as
      the data collection tools. RESULTS: Information need score averages (x?:3.72+/
      0.19) of women included in the research sampling were found to be higher than
      their score averages of support needs (x?:3.24+/-0.41). CONCLUSION: Information
      needs which were indicated by women as very important were related to treatment,
      symptoms of breast cancer and breast self examination (BSE), while support needs
      which were indicated by women as very important were learning how to perform BSE,
      women's anxiety for themselves and their relatives regarding breast cancer and
      having their breasts examined by a health professional. It is recommended that
      nurses and other medical staff should give information to women whose first
      degree relatives have breast cancer about the disease, its etiology, scanning,
      diagnosis, treatment options and protection as well as prevention.

PMID- 23167368
TI  - Time trends of esophageal cancer mortality in Linzhou city during the period 1988
      2010 and a Bayesian approach projection for 2020.
AB  - In recent decades, decreasing trends in esophageal cancer mortality have been
      observed across China. We here describe esophageal cancer mortality trends in
      Linzhou city, a high-incidence region of esophageal cancer in China, during 1988
      2010 and make a esophageal cancer mortality projection in the period 2011-2020
      using a Bayesian approach. Age standardized mortality rates were estimated by
      direct standardization to the World population structure in 1985. A Bayesian age
      period-cohort (BAPC) analysis was carried out in order to investigate the effect
      of the age, period and birth cohort on esophageal cancer mortality in Linzhou
      during 1988-2010 and to estimate future trends for the period 2011-2020. Age
      adjusted rates for men and women decreased from 1988 to 2005 and changed little
      thereafter. Risk increased from 30 years of age until the very elderly. Period
      effects showed little variation in risk throughout 1988-2010. In contrast, a
      cohort effect showed risk decreased greatly in later cohorts. Forecasting, based
      on BAPC modeling, resulted in a increasing burden of mortality and a decreasing
      age standardized mortality rate of esophageal cancer in Linzhou city. The
      decrease of esophageal cancer mortality risk since the 1930 cohort could be
      attributable to the improvements of social- economic environment and lifestyle.
      The standardized mortality rates of esophageal cancer should decrease
      continually. The effect of aging on the population could explain the increase in
      esophageal mortality projected for 2020.

PMID- 23167369
TI  - Post-operative treatment with cisplatin and vinorelbine in Chinese patients with
      non-small cell lung cancer: a clinical prospective analysis of 451 patients.
AB  - PURPOSE: To determine the efficacy of post-operative chemotherapy with cisplatin
      plus vinorelbine (NP) in Chinese patients with non-small cell lung cancer
      (NSCLC). METHODS: A total of 451 patients with NSCLCs at stages I, II, and IIIA
      after surgical resection were treated with cisplatin plus vinorelbine for 4
      cycles or volunteers observed between January 2002 and November 2004 and were
      followed for five years. The therapeutic efficacy was evaluated with reference to
      overall survival (OS) and disease-free survival (DFS), and adverse effects were
      also recorded. Potential factors affecting the lengths of OS and DFS were
      analyzed by multivariate analysis. RESULTS: Most patients (86.7%) completed at
      least 4 cycles of treatment. Patients with chemotherapy survived significantly
      longer than those in the observation group (p<0.001). The absolute improvements
      in the 2 and 5-year OS were 3.8% [hazard ratio (HR) =0.674, 95% confidence
      interval (CI): 0.554-0.820, P<0.0001] and 13.0% (HR=0.732, 95% CI: 0.579-0.926,
      P=0.009), respectively. The improvement at 4-year DFS was 2.1% (HR=0.327, 95% CI:
      0.214-0.500, P<0.0001). Stratification analysis revealed that older age,
      histological type, pathological degree, but not the gender and smoking status,
      are independent factors affecting the length of survival in this population. Many
      patients (63.3%) had grade 1-III tolerable adverse effects, and there was no
      treatment-related death. CONCLUSIONS: Post-operative chemotherapy with NP regimen
      is effective and tolerable in Chinese patients with NSCLC.

PMID- 23167370
TI  - Causes of delay in seeking treatment in patients with breast cancer in Iran: a
      qualitative content analysis study.
AB  - BACKGROUND: In the Middle East, including Iran, breast cancer is the most
      frequent malignancy among women. Without treatment, a malignant breast tumor
      advances in stage, diminishing a woman's chances of survival. In this study we
      aimed to gain insight into the causes of delay in seeking treatment in patients
      with breast cancer. METHODS: The participants in this qualitative, content
      analysis study were 10 women in whom a diagnosis of breast cancer in the stages
      of II b, III or IIV had been made. They were selected from patients of a major
      oncology clinic in Kerman, Iran. Data were collected by means of semi-structured
      interviews that lasted between 20 to 30 minutes. Sampling was discontinued when
      data saturation was achieved. Content analysis was conducted by classifying the
      data into themes and sub-themes. RESULTS: The results of our study revealed
      several factors that interfered with patients' professional consultation seeking
      and prompt treatment. These factors included; lack of knowledge, fear of being
      diagnosed with cancer, not seeing oneself at risk, mental preoccupation and wrong
      diagnosis by physicians. CONCLUSIONS: This study suggests that women and even
      physicians need further information about breast cancer symptoms. Women need
      encouragement to seek medical advice when they encounter suspicious symptoms.
      Additionally, women may benefit from awareness of the pros of early detection and
      reassurance about the improvements in the success of breast cancer treatment.

PMID- 23167371
TI  - Epidemiological pattern of breast cancer in Iranian women: is there an ethnic
      disparity?
AB  - INTRODUCTION: Northeastern Iran is known as a high risk area of upper
      gastrointestinal cancers. Recent reports have suggested a declining trend for
      these cancers as well as an increase in the incidence of other malignancies
      including breast cancer. Our present aim was to describe the epidemiological
      pattern of breast cancer in this region during 2004-2009. METHODS: All new cancer
      cases from public and private diagnostic and therapeutic centers of Golestan
      province were registered. A structured questionnaire was prepared and used based
      on the standards of the International Association of Cancer Registries. The
      international classification of diseases for oncology was considered for coding.
      Age standardized incidence rates (ASR) of breast cancer were calculated. RESULTS:
      A total of 11,038 new cancer cases were registered during 2004-2009, of which,
      1,101 (10%) were females with breast cancer. The median age of the breast cancer
      patients was 46 years. The ASR for breast cancer was 28 per 100,000 person-years.
      We found an unusual rapid increase in breast cancer rate at the age of 25 years.
      The ASR of breast cancer was significantly lower in females from Turkmen
      ethnicity and those from rural areas (P value <0.01). CONCLUSION: Our study
      showed high rate of breast cancer in Golestan province of Iran. We found an
      unusual peak of breast cancer in young women. So, the age of starting screening
      programs may need to be revised in this area. The rate of breast cancer was
      significantly lower in women from Turkmen ethnicity. Further studies are
      warranted to clarify the role of important determinants, especially regarding the
      ethnic disparity, on breast cancer in this region.

PMID- 23167372
TI  - Improved accuracy of cytodiagnosis using the Kato self-collection devise: the
      usefulness of smear preparation in liquid-based cytology methods.
AB  - OBJECT: In the present study, we compared the positive cytodiagnostic test rates
      with discrepancies using self-collection devices for cervical cancer screening.
      We made this survey to examine whether or not our self- smear preparation method
      using the Kato self-collection device contributed to an improved rate of
      detecting atypical cells compared with existing recommended preparation methods.
      METHODS: Specimens were collected at 14 facilities handling self-collection
      methods, and samples were collected by a physician in 2 facilities. The chi-
      squared test was performed using the SPSS ver. 20 statistical software to
      determine the relationships between the positive cytodiagnostic rate, specimen
      preparation methods, and self-collection devices. RESULTS: Collecting cells using
      the Kato self-collection device and preparing liquid-based specimens, we obtained
      a significantly higher rate of positive cytodiagnosis and our results were equal
      to those obtained with the direct method. CONCLUSIONS: Taking into consideration
      increased needs for screening using the self-collection method in future, with
      even more improved test accuracy, a screening test that is acceptable to society
      needs to be established.

PMID- 23167373
TI  - Ovarian metastasis and other ovarian neoplasms in women with cervical cancer
      stage IA-IIA.
AB  - OBJECTIVES: To determine the prevalence and predicting factors of ovarian
      metastasis, and evaluate the histology of other ovarian neoplasms in women with
      early-stage cervical cancer. METHODS: The medical records of women with cervical
      cancer stage IA-IIA who underwent primary surgical treatment at Siriraj Hospital,
      Mahidol University from January 2007 to December 2011 were used for the study.
      Demographic, clinical and histopathologic data of the women who underwent
      salpingo-oophorectomy were reviewed. RESULTS: Of 264 women, the mean age was 52.3
      years. The types of hysterectomy procedures were composed of 210 radical
      hysterectomy, 9 modified radical hysterectomy, 40 simple hysterectomy, and 5
      abandoned hysterectomy. The prevalence of ovarian metastasis was 0.76% (2/264).
      All of ovarian metastatic patients were older than 60 years old, postmenopause,
      and had macroscopical stage IB1 cervical cancer. Others ovarian tumors were found
      in 7 patients including 1 synchronous ovarian carcinoma, 1 serous cystadenoma, 1
      fibroma, and 4 teratoma. CONCLUSIONS: In cases of early-stage cervical carcinoma
      of the population studied, ovarian preservation could be another option in <60
      year-old patients, with non-neuroendocrine cell type, stage IA, and no
      extracervical or ovarian lesions.

PMID- 23167374
TI  - Intervention effects of nedaplatin and cisplatin on proliferation and apoptosis
      of human tumour cells in vitro.
AB  - OBJECTIVE: To study synergistic effects of nedaplatin and cisplatin on three
      human carcinoma cell lines (esophageal carcinoma cell line Eca-109, ovarian
      carcinoma Skov-3 and cervical carcinoma Hela). METHODS: Inhibition effects were
      evaluated by MTT assay and cell apoptosis was detected by flow cytometry. In
      addition, changes of Ki-67, Bax and Bcl-2 at mRNA and protein levels were
      quantified by RT-PCR and Western blotting. RESULTS: Growth inhibition in each
      cell lines was dose-dependent after exposure to nedaplatin or cisplatin alone.
      The interaction of the two drugs was synergistic at higher concentrations
      according to the median-effect principle. The inhibition rates with nedaplatin,
      cisplatin and combined treatment were 41.9+/-4.1%, 47.4+/-2.9%, 52.5+/-0.9%(Eca
      109), 39.0+/-1.26%, 45.0+/-1.45% , 56.2+/-1.44% (Skov-3) and 44.8+/-2.11%, 46.9+/
      0.99%, 56.6+/-1.83% (Hela) respectively, with increase in apoptosis. Compared
      with the nedaplatin or cisplatin alone treatment group, the combinative treatment
      group's Ki-67 and bcl-2 mRNA (protein) expression was decreased while that of Bax
      mRNA (protein) was increased. CONCLUSION: Compared to the effects of nedaplatin
      or cisplatin alone at high concentrations, combination of nedaplatin and
      cisplatin at low concentrations proved to be much more effective for inhibition
      of proliferation and the induction of apoptosis in the Eca-109, Skov-3 and Hela
      cell lines.

PMID- 23167375
TI  - Role of endoscopic ultrasound in evaluation of pancreatic neuroendocrine tumors-
      report of 22 cases from a tertiary center in Iran.
AB  - BACKGROUND: The pancreatic neuroendocrine tumor (pNET) is relatively rare and
      generally felt to follow an indolent course. EUS has an important role in
      detection of pNET. This is a review of clinical and radiological presentation and
      pathologic reports of 22 patients with pNET. PATIENTS AND METHODS: In this study
      we analyzed clinical and radiological presentations and pathologic reports of all
      relevant cases who were referred to Taleghani hospital for 3 years since 2008.
      RESULTS: A total of 22 patients 28-74 years old (mean=49) were enrolled between
      2008 and 2011. Among the total, 13 (59%) were male, 9 (41%) were female and 16
      (72.7%) had functional tumors. The results of CT were negative in 12 (54%) cases
      but EUS was capable of detecting the lesions in these patients, cysts being found
      in 4 (19%) patients. CONCLUSION: EUS is a highly sensitive procedure for the
      localization of functional pNETs and especially insulinomas. Nonfunctional tumors
      were detected in more advanced and late stages and cystic lesions were more
      common in this group.

PMID- 23167376
TI  - Elevated serum haptoglobin is associated with clinical outcome in triple-negative
      breast cancer patients.
AB  - BACKGROUND: Breast cancer is the most common malignancy with the highest
      incidence rates among women worldwide. Triple-negative breast cancer (TNBC)
      disease is diagnosed more frequently in younger women, and is associated with a
      poor prognosis. Elevated levels of serum haptoglobin protein (Hp) are observed in
      many malignant diseases including breast cancer. We evaluated the expression and
      prognostic value of Hp among patients with TNBC. MATERIALS AND METHODS: Serum Hp
      levels were determined by Elisa in 41 patients with TNBC and 10 normal
      individuals. Hp status was correlated with other clinico-pathological parameters
      including patient survival. RESULTS: Of the 41 patients with TNBC, Hp over
      expression was detected in 24 (59%) by Elisa. Hp up-regulation was confirmed by
      Elisa based quantification in the serum of 41 TNBC patients against lower grades
      and 10 normal individuals. Survival analysis revealed that Hp (p=2.016x10-5),
      stage (p=2.166x10-5), distant metastasis (p=2.217x10-5), tumor size (p=1.053x10
      5), and tumor grade (p=0.001), correlated with patient survival on univariate
      analysis. Multivariate analysis revealed that Hp (p=0.001), and grade of the
      disease (p=0.008) were independent predictors of survival. CONCLUSION: Our
      results indicate that serum levels of Hp may play a role as a potential serum
      biomarker and prognostic indicator among TNBC patients. Thus, Hp may present a
      new promising prognostic biomarker in TNBC patients, but independent validations
      are now necessary for confirmation.

PMID- 23167377
TI  - Serum level of MMP-3 in patients with oral squamous cell carcinoma--lack of
      association with clinico-pathological features.
AB  - BACKGROUND: MMP-3 is a proteolytic enzyme of the matrix metalloproteinase family.
      Protein degradation which is their fundamental action regulates different
      activities of tumor cell such as their growth, differentiation, apoptosis,
      migration, invasion, angiogenesis as well as their resistance to the immune
      system. AIM: The aim of this study was to determine MMP-3 serum levels in
      patients with OSCC and investigate if they correlate with clinicopathological
      features. METHOD AND MATERIALS: Using an ELISA kit, we assessed and compared the
      circulating levels of MMP-3 in blood serum of 45 oral squamous cell carcinoma
      patients with 45 healthy control samples. RESULTS: The serum MMP-3 level in OSCC
      patients was significantly higher (9.45+/-4.6 ng/ml) than healthy controls (5.9+/
      3.6 ng/ml, p<0.001), especially in females and in older patients. However, there
      was no apparent correlation in serum MMP-3 concentration with the clinico
      pathological features such as tumor location, stage, tumor size, nodal status,
      distant metastasis, histological grade and smoking. DISCUSSION: This result
      suggests that the measurement of serum MMP-3 concentration might be helpful to
      diagnose OSCC but not to predict prognosis.

PMID- 23167378
TI  - Impact of CYP2D6 polymorphisms on tamoxifen responses of women with breast
      cancer: a microarray-based study in Thailand.
AB  - This study was designed to investigate the frequency of CYP2D6 polymorphisms and
      evaluate the association between genetic polymorphisms of CYP2D6 and tamoxifen
      therapeutic outcome in Thai breast cancer patients. We recruited 48 breast cancer
      patients who received adjuvant tamoxifen for evaluating CYP2D6 genetic
      polymorphisms using microarray-based technology. Associations between genotypes
      phenotypes and disease free survival were analyzed. Median follow up time was 5.6
      years. The mean age of the subjects was 50 years. The 3 common allelic
      frequencies were 43.8% (*10), 36.5 (*1) and 10.4% (*2) which are related to
      extensive metabolizer (EM) and intermediate metabolizer (IM) with 70.8% and 29.2
      %, respectively. No association between CYP2D6 genotypes and DFS was
      demonstrated. Nevertheless, exploratory analysis showed statistically significant
      shorter DFS in the IM group of post-menopause patients (HR, 6.85; 95% CI, 1.48 
      31.69; P = 0.005). Furthermore, we observed statistically significant shorter DFS
      of homozygous CYP2D6*10 when compared with heterozygous CYP2D6*10 and other
      genotypes (P=0.005). CYP2D6*10 was the most common genotype in our subjects. Post
      menopause patients with homozygous CYP2D6*10 and IM have shorter DFS. To confirm
      this relationship, larger samples and comprehensively designed trials in Thailand
      are required.

PMID- 23167379
TI  - Oleuropein induces anti-metastatic effects in breast cancer.
AB  - Breast cancer causes death due to distant metastases in which tumor cells produce
      matrix metalloproteinase (MMP) enzymes which facilitate invasion. Oleuropein, the
      main olive oil polyphenol, has anti-proliferative effects. This study aimed to
      investigate the effect of oleuropein on the metastatic and anti-metastatic gene
      expression in the MDA human breast cancer cell line. We evaluated the MMPs and
      TIMPs gene expression by semi-quantitative reverse transcriptase polymerase chain
      reaction (RT-PCR) in treated and untreated cells. This study demonstrated that OL
      may induce anti-metastatic effects on human breast cancer cells. We found that
      TIMP1,-3, and -4 were over-expressed after all periods of incubation in treated
      cancer cells compared to untreated cells, while MMP2 and MMP9 genes were down
      regulated, at least initially. Treatment of breast cancer cells with oleuropein
      could help in prevention of cancer metastasis by increasing the TIMPs and
      suppressing the MMPs gene expressions.

PMID- 23167380
TI  - Psychological treatment for pain among cancer patients by rational-emotive
      behavior therapy--efficacy in both India and Iran.
AB  - The aim of the present study is to find out the influence of rational-emotive
      behavior therapy (REBT) on pain intensity among cancer patients in India and
      Iran. The study followed a quasi-experimental, pre-post test, carried out with a
      sample of 88 cancer patients, aged 21-52 years, referred to the Baharat cancer
      hospital of Mysore in India and Shahidzade hospital of Behbahan in Iran. They
      were randomly assigned to the experimental (n=India 21; Iran 22) and control
      (n=India 22; Iran 23) groups. Pain was measured with the McGill Pain
      Questionnaire- MPQ (1975), the intervention by REBT has given to the experimental
      group for 45 days (ten sessions) and at the end of intervention, the pain of
      patients was again evaluated. Concerning to hypothesis of the study, two
      independent sample T test and three ways mixed ANOVA is used to analyze the data.
      Results showed that the experimental group in post test had less pain than the
      control group, but there were no statistically significant differences between
      Indian and Iranian patients in pain perception. With respect the outcome of
      study, it has realized that REBT can be used in hospitals and other psychological
      clinics to reduce the pain of cancer patients.

PMID- 23167381
TI  - Clinicopathologic importance of women with squamous cell carcinoma cytology on
      Siriraj liquid-based cervical cytology.
AB  - OBJECTIVES: The purposes of this study were to determine the prevalence and
      predictive value to detect significant neoplasia and invasive lesions, and to
      evaluate the correlation between clinical and histopathology of women with
      squamous cell carcinoma (SCCA) on Siriraj liquid-based cervical cytology (Siriraj
      LBC). METHODS: The computerized database of women who underwent Siriraj-LBC at
      Siriraj Hospital, Mahidol University from January 2007 to December 2010 were
      retrieved. The hospital records of women with SCCA cytology were reviewed.
      RESULTS: The prevalence of SCCA cytology was 0.07%. A total of 86 women, mean age
      was 58.1 years. Sixty-one women (70.9%) were post-menopausal. Overall significant
      pathology and invasive gynecologic cancer were detected in 84 women (97.7%) and
      71 women (82.5%), respectively. The positive predictive values for detection of
      significant neoplasia and invasive lesion were 97.7% and 82.6%, respectively. The
      cervical cancer was diagnosed in 69 women and among these 58 women were SCCA.
      Thirteen women (15.1%) had cervical intraepithelial neoplasia (CIN) 3 and two
      women (2.3%) had cervicitis. The sensitivity and specificity of colposcopy for
      cervical cancer detection in SCCA cytology were 83.3% and 75%, respectively.
      Median follow up period was 17.6 months and 64 patients were alive without
      cytologic abnormality. CONCLUSIONS: The final histopathology of SCCA cytology in
      our populations demonstrated a wide variety, from cervicitis to invasive cancer
      and the most common diagnosis was invasive cervical cancer. Colposcopy with
      biopsy and/or endocervical curettage and loop electrosurgical excision procedure
      should be undertaken to achieve histologic diagnosis.

PMID- 23167382
TI  - Clinicopathological features in bilateral breast cancer.
AB  - INTRODUCTION AND PURPOSE: The frequency of bilateral breast cancer is 1.4-11.0%
      among all breast cancers. It can present as synchronous (SC) or metachronous
      (MC). Data regarding clinical course of bilateral breast cancer are scarce. In
      this study, we therefore evaluated demographic, pathological and clinical
      characteristics, treatments and responses in bilateral breast cancer cases;
      making distinctions between metachronous-synchronous and comparing with historic
      one-sided data for the same parameters. MATERIALS AND METHODS: One hundred fifty
      bilateral breast cancer cases from ten different centers between 2000 and 2011
      were retrospectively scanned. Age of the cases, family history, menopausal
      status, pathological features, pathological stages, neoadjuvant, surgery,
      adjuvant and palliative chemotherapy/radiotherapy were examined in the context of
      the first and second occurrence and discussed with reference to the literature.
      RESULTS: Metachronous and synchronous groups showed similar age, menopausal
      status, tumor type, HER2/neu expression; the family history tumor grade, tumor
      stage, ER-negativity rate, local and distant metastases rates, surgery, adjuvant
      chemotherapy application rates were identified as significantly different.
      Palliative chemotherapy response rate was greater in the metachronous group but
      median PFS rates did not differ between the groups. CONCLUSION: Although
      bilateral breast cancer is not frequent, MC breast cancer is different from SC
      breast cancer by having more advanced grade, stage, less ER expression, more
      frequent rates of local relapse and distant metastasis and better response to
      chemotherapy in case of relapse/metastasis.

PMID- 23167383
TI  - Prostate cancer in younger and older patients: do we treat them differently?
AB  - Diagnostic and therapeutic strategies of prostate cancer may largely influenced
      by patients' age at presentation. This study is aimed to evaluate the
      characteristics, diagnostic and treatment strategies in prostate cancer patients
      in our centres. A cross-sectional analytic study of prostate cancer data in two
      main referral cancer centres, Cipto Mangunkusumo General Hospital and Dharmais
      National Cancer Centre from 1995-2010, was therefore performed. Patients were
      divided into 2 sub-populations; below 60 years (younger patients) and 75 years
      old and above (older patients). PSA levels, diagnostic modalities, Gleason score
      and therapeutic options were analysed for both and compared using bivariate
      analysis. 152 patients were <60 years and 210 were >=75 years. There was no
      statistical difference in mean PSA level (797.9ng/mL vs 345.3 ng/mL,
      respectively; p>0.05) and diagnosis was made by biopsy in majority of patients in
      both groups (68.2% and 71.6% in younger and older groups respectively). Most
      presented with an advanced disease stage (65.1% and 66.0%, respectively) and
      there was no statistically significant difference in mean Gleason scores f (8.1
      vs 7.7; p>0.05). Primary androgen deprivation therapy (PADT) was the main
      treatment for overall patients (48.0% and 50.7%, respectively). Radiotherapy and
      radical prostatectomy are the main therapeutic modalities for younger patients
      with local and locally advanced disease (39.6% and 35.4% respectively), while the
      majority of older patients with the same disease stage were treated with
      radiotherapy and PADT (45.8% and 39.0% respectively). Differences observed in
      treatment modalities were statistically significant (p<0.0003). We conclude that
      there is no difference in disease clinical aggressiveness of the two groups but
      significant differences were obseved in therapeutic strategies utilised with
      younger and older patients.

PMID- 23167384
TI  - Molecular characterization of FLT3 mutations in acute leukemia patients in
      Pakistan.
AB  - Fms-like tyrosine kinase 3 (FLT3) performs a vital role in the pathogenesis of
      hematopoietic malignancies. Therefore in recent times, the focus of several
      studies was on use of FLT3 as a prognostic marker. The present study investigated
      the molecular characterization and incidence of FLT3 mutations in acute leukemia
      patients in Pakistan. A total of 55 patients were studied, of which 25 were
      suffering from acute lymphoblastic leukemia (ALL) and 30 were suffering from
      acute myeloid leukemia (AML). The polymerase chain reaction demonstrated FLT3/
      ITD mutations in 1 (4%) of 25 ALL patients, a male with the L2 subtype. In AML
      cases the rate was 4 (13.3%) of 30, three males and one female. The AML-M4
      subtype was found in three and the AML M2 subtype in the other. In the AML cases,
      a statistically significant (p=0.009) relationship was found between WBC (109/L)
      and FLT3/ ITD positivity. However, no significant relationship was found with
      other clinical parameters (p>0.05). In acute myeloid leukemia (AML) FLT3/ITD+
      mutation was more prevalent in elderly patients 31-40 age groups, 21-30 and 51-60
      age groups respectively. In acute lymphoblastic leukemia (ALL) statistically no
      significant relationship was found between clinical features and FLT3/ITD
      positivity (p>0.05). However, in acute lymphoblastic leukemia (ALL) FLT3/ITD+
      mutation was more commonly found in age groups of 21-30.

PMID- 23167385
TI  - Poor treatment outcome of neuroblastoma and other peripheral nerve cell tumors
      may be related to under usage of radiotherapy and socio-economic disparity: a US
      SEER data analysis.
AB  - PURPOSE: This study used receiver operating characteristic curve to analyze
      Surveillance, Epidemiology and End Results (SEER) neuroblastoma (NB) and other
      peripheral nerve cell tumors (PNCT) outcome data. This study found under usage of
      radiotherapy in these patients. MATERIALS AND METHODS: This study analyzed socio
      economic, staging and treatment factors available in the SEER database for NB and
      other PNCT. For the risk modeling, each factor was fitted by a generalized jinear
      model to predict the outcome (soft tissue specific death, yes/no). The area under
      the receiver operating characteristic curve (ROC) was computed. Similar strata
      were combined to construct the most parsimonious models. A random sampling
      algorithm was used to estimate the modeling errors. Risk of neuroendocrine (other
      endocrine including thymus as coded in SEER) death was computed for the
      predictors. RESULTS: There were 5261 patients diagnosed from 1973 to 2009 were
      included in this study. The mean follow up time (S.D.) was 83.8 (97.6) months.
      The mean (SD) age was 18 (25) years. About 30.45% of patients were un-staged. The
      SEER staging has high ROC (SD) area of 0.58 (0.01) among the factors tested. We
      simplified the 4-layered risk levels (local, regional, distant, un-staged/others)
      to a simpler 3-tiered model with comparable ROC area of 0.59 (0.01). Less than
      50% of PNCT patients received radiotherapy (RT) including the ones with localized
      disease. This avoidance of RT use occurred in adults and children. CONCLUSION:
      The high under-staging rate may have prevented patients from selecting definitive
      radiotherapy (RT) after surgery. Using RT for, especially, adult PNCT patients is
      a potential way to improve outcome.

PMID- 23167386
TI  - Comparison of teaching about breast cancer via mobile or traditional learning
      methods in gynecology residents.
AB  - INTRODUCTION: Mobile learning enables users to interact with educational
      resources while in variable locations. Medical students in residency positions
      need to assimilate considerable knowledge besides their practical training and we
      therefore aimed to evaluate the impact of using short message service via cell
      phone as a learning tool in residents of Obstetrics and Gynecology in our
      hospital. METHODS: We sent short messages including data about breast cancer to
      the cell phones of 25 residents of gynecology and obstetrics and asked them to
      study a well-designed booklet containing another set of information about the
      disease in the same period. The rate of learning derived from the two methods was
      compared by pre- and post-tests and self-satisfaction assessed by a relevant
      questionnaire at the end of the program. RESULTS: The mobile learning method had
      a significantly better effect on learning and created more interest in the
      subject. CONCLUSION: Learning via receiving SMS can be an effective and appealing
      method of knowledge acquisition in higher levels of education.

PMID- 23167387
TI  - Cytotoxicity, toxicity, and anticancer activity of Zingiber officinale Roscoe
      against cholangiocarcinoma.
AB  - Cholangiocarcinoma (CCA) is an uncommon adenocarcinoma which arises from the
      epithelial cells of the bile ducts. The aim of the study was to investigate the
      cytotoxicity, toxicity, and anticancer activity of a crude ethanolic extract of
      ginger (Zingiber officinale Roscoe) against CCA. Cytotoxic activity against a CCA
      cell line (CL-6) was assessed by calcein-AM and Hoechst 33342 assays and anti
      oxidant activity was evaluated using the DPPH assay. Investigation of apoptotic
      activity was performed by DNA fragmentation assay and induction of genes that may
      be involved in the resistance of CCA to anticancer drugs (MDR1, MRP1, MRP2, and
      MRP3) was examined by real-time PCR. To investigate anti-CCA activity in vivo, a
      total of 80 OV and nitrosamine (OV/ DMN)-induced CCA hamsters were fed with the
      ginger extract at doses of 1000, 3000, and 5000 mg/kg body weight daily or every
      alternate day for 30 days. Control groups consisting of 10 hamsters for each
      group were fed with 5-fluorouracil (positive control) or distilled water
      (untreated control). Median IC50 (concentration that inhibits cell growth by 50%)
      values for cytotoxicity and anti-oxidant activities of the crude ethanolic
      extract of ginger were 10.95, 53.15, and 27.86 MUg/ml, respectively. More than
      ten DNA fragments were visualized and up to 7-9 fold up-regulation of MDR1 and
      MRP3 genes was observed following exposure to the ethanolic extract of ginger.
      Acute and subacute toxicity tests indicated absence of any significant toxicity
      at the maximum dose of 5,000 mg/kg body weight given by intragastric gavage. The
      survival time and survival rate of the CCA-bearing hamsters were significantly
      prolonged compared to the control group (median of 54 vs 17 weeks). Results from
      these in vitro and in vivo studies thus indicate promising anticancer activity of
      the crude ethanolic extract of ginger against CCA with the absence of any
      significant toxicity. Moreover, MDR1 and MRP3 may be involved in conferring
      resistance of CCA to the ginger extract.

PMID- 23167388
TI  - Weighted gene co-expression network analysis in identification of endometrial
      cancer prognosis markers.
AB  - OBJECTIVE: Endometrial cancer (EC) is the most common gynecologic malignancy.
      Identification of potential biomarkers of EC would be helpful for the detection
      and monitoring of malignancy, improving clinical outcomes. METHODS: The Weighted
      Gene Co-expression Network Analysis method was used to identify prognostic
      markers for EC in this study. Moreover, underlying molecular mechanisms were
      characterized by KEGG pathway enrichment and transcriptional regulation analyses.
      RESULTS: Seven gene co-expression modules were obtained, but only the turquoise
      module was positively related with EC stage. Among the genes in the turquoise
      module, COL5A2 (collagen, type V, alpha 2) could be regulated by PBX (pre-B-cell
      leukemia homeobox 1)1/2 and HOXB1(homeobox B1) transcription factors to be
      involved in the focal adhesion pathway; CENP-E (centromere protein E, 312kDa) by
      E2F4 (E2F transcription factor 4, p107/p130-binding); MYCN (v-myc
      myelocytomatosis viral related oncogene, neuroblastoma derived [avian]) by PAX5
      (paired box 5); and BCL-2 (B-cell CLL/ lymphoma 2) and IGFBP-6 (insulin-like
      growth factor binding protein 6) by GLI1. They were predicted to be associated
      with EC progression via Hedgehog signaling and other cancer related-pathways.
      CONCLUSIONS: These data on transcriptional regulation may provide a better
      understanding of molecular mechanisms and clues to potential therapeutic targets
      in the treatment of EC.

PMID- 23167389
TI  - Analysis of esophageal cancer time trends in China, 1989- 2008.
AB  - National cancer incidence data were utilized to analyze trends in esophageal
      cancer incidence in China in order to provide basic information for making cancer
      control strategy. We retrieved and re-sorted valid esophageal cancer incidence
      data from National Central Cancer Registry Database over 20 years period from
      1989 to 2008. Crude incidence and age-standardized incidence rates were
      calculated for analysis, with annual percent change estimated by Joinpoint
      software for long term trend analysis. The crude incidence rate of esophageal
      cancer was found to have remained relatively stable in both urban and rural areas
      over the 20 year period. Age standardized incidence rate (ASR) in cancer
      registration areas decreased from 39.5/100,000 in 1989 to 23.0/100,000 in 2008 in
      all areas (AAPC=-3.3%, 95% CI:-2.8~-3.7). The trend was no change in urban areas
      and 2.1% average annual decrease observed in rural aras. Before the year of 2000,
      esophageal cancer incidence rates significant decreased with 2.8% annually and
      then the rates kept stable. Over 20 years from 1989 to 2008, esophageal cancer
      age standardized incidence rate in cancer registration areas decreased with time.
      However, esophageal cancer is still a big issue and efforts for control should be
      continuously enhanced. Cancer registration is playing an important role in cancer
      control with the number of registries increasing and data quality improving in
      China.

PMID- 23167390
TI  - Is level V dissection necessary for low-risk patients with papillary thyroid
      cancer metastasis in lateral neck levels II, III, and IV.
AB  - Whether it is beneficial to dissect level V in papillary thyroid cancer (PTC)
      patients with positive lateral neck lymph nodes at levels II-IV is still
      controversial, especially for low risk cases. In this study, we reviewed the
      medical records of 47 patients who underwent 47 ipsilateral selective lateral
      neck dissections (levels II-IV) for previously untreated papillary thyroid
      carcinomas between October 2006 and October 2008 to assist in establishing the
      optimal strategy for lateral neck dissection in low risk PTC patients with
      clinically negative level V nodes. All 47 patients were confirmed to have
      positive lymph nodes pathologically. Seventeen (36.12%), 36 (76.6%), and 34
      (72.34%) patients had positive lymph nodes in levels II, III, and IV,
      respectively. The mean number of pathologically positive lymph nodes was 1.7 in
      level II, 2.9 in level III, 2.8 in level IV. No death and distant metastasis were
      recorded during follow up period. Just 2 patients exhibited recurrence to lymph
      nodes, and only one showed nodal recurrence in ipsilateral level V, who had
      positive lymph nodes in all of levels II, III, and IV at initial neck surgery. In
      conclusion, for PTC low risk patients with clinically negative lymph nodes in
      level V, non-performance of level V dissection would still achieve good survival
      results as traditional modified radical neck dissection, with a "wait and see"
      strategy to be recommended.

PMID- 23167391
TI  - Risk of treatment related death and febrile neutropaenia with taxane-based
      adjuvant chemotherapy for breast cancer in a middle income country outside a
      clinical trial setting.
AB  - BACKGROUND: The risk of treatment-related death (TRD) and febrile neutropaenia
      (FN) with adjuvant taxane- based chemotherapy for early breast cancer is unknown
      in Malaysia despite its widespread usage in recent years. This study aims to
      determine these rates in patients treated in University Malaya Medical Centre
      (UMMC). PATIENTS AND METHODS: Patients who were treated with adjuvant taxane
      based chemotherapy for early breast cancer stages I, II or III from 2007-2011 in
      UMMC were identified from our UMMC Breast Cancer Registry. The TRD and FN rates
      were then determined retrospectively from medical records. TRD was defined as
      death occurring during or within 30 days of completing chemotherapy as a
      consequence of the chemotherapy treatment. FN was defined as an oral temperature
      >38.5 degrees C or two consecutive readings of >38.0 degrees C for 2 hours and an
      absolute neutrophil count <0.5x109/L, or expected to fall below 0.5x109/L.
      RESULTS: A total of 622 patients received adjuvant chemotherapy during this
      period. Of these patients 209 (33.6%) received taxane-based chemotherapy. 4
      taxane-based regimens were used namely the FEC-D, TC, TAC and AC-PCX regimens.
      The commonest regimen employed was the FEC-D regimen accounting for 79.9% of the
      patients. The FN rate was 10% and there was no TRD. CONCLUSION: Adjuvant taxane
      based chemotherapy in UMMC for early breast cancer has a FN rate of 10%. Primary
      prophylactic G-CSF should be considered for patients with any additional risk
      factor for FN.

PMID- 23167392
TI  - MTHFR gene polymorphisms are not involved in pancreatic cancer risk: a meta
      analysis.
AB  - PURPOSE: Methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms have been
      reported to be associated with pancreatic cancer, but the published studies have
      yielded inconsistent results. This study assessed the relationship between MTHFR
      gene polymorphisms and the risk for pancreatic cancer using a meta-analysis
      approach. METHODS: A search of Google scholar, PubMed, Cochrane Library and CNKI
      databases before April 2012 was performed, and then associations of the MTHFR
      polymorphisms with pancreatic cancer risk were summarized. The association was
      assessed by odds ratios (ORs) with 95% confidence intervals (CIs). Publication
      bias was also calculated. RESULTS: Four relative studies on MTHFR gene
      polymorphisms (C667T and A1298C) were included in this meta-analysis. Overall,
      C667T (TT vs. CC:OR=1.61,95%CI=0.78-3.34; TT vs. CT: OR=1.41,95%CI=0.88-2.25;
      Dominant model:OR=0.68,95%CI=0.40-1.17; Recessive model: OR=0.82,95%CI=0.52-1.30)
      and A1298C (CC vs. AA:OR=1.01,95%CI=0.47-2.17; CC vs. AC: OR=0.99,95%CI=0.46
      2.14; Dominant model:OR=1.01, 95%CI=0.47-2.20; Recessive model:
      OR=1.01,95%CI=0.80-1.26) did not increase pancreatic cancer risk. CONCLUSIONS:
      This meta-analysis indicated that MTHFR polymorphisms (C667T and A1298C) are not
      associated with pancreatic cancer risk.

PMID- 23167393
TI  - Tobacco control law enforcement and compliance in Odisha, India--implications for
      tobacco control policy and practice.
AB  - INTRODUCTION: Tobacco use is a leading cause of deaths and disabilities in India,
      killing about 1.2 lakh people in 2010. About 29% of adults use tobacco on a daily
      basis and an additional 5% use it occasionally. In Odisha, non-smoking forms are
      more prevalent than smoking forms. The habit has very high opportunity cost as it
      reduces the capacity to seek better nutrition, medical care and education. In
      line with the WHO Framework Convention on Tobacco Control (FCTC), the Cigarettes
      and Other Tobacco Products Act (COTPA) is a powerful Indian national law on
      tobacco control. The Government of Odisha has shown its commitment towards
      enforcement and compliance of COTPA provisions. In order to gauge the perceptions
      and practices related to tobacco control efforts and level of enforcement of
      COTPA in the State, this cross-sectional study was carried out in seven selected
      districts. MATERIALS AND METHODS: A semi-structured interview schedule was
      developed, translated into Odiya and field-tested for data collection. It mainly
      contained questions related to knowledge on provisions of section 4-7 of COTPA
      2003, perception about smoking, chewing tobacco and practices with respect to
      compliance of selected provisions of the Act. 1414 samples were interviewed.
      RESULTS: The highest percentage of respondents was from the government
      departments. 70% of the illiterates consumed tobacco as compared to 34% post
      graduates. 52.1% of the respondents were aware of Indian tobacco control laws,
      while 80.8% had knowledge about the provision of the law prohibiting smoking in
      public places. However, 36.6% of the respondents reported that they had 'very
      often' ' seen tobacco products being sold 'to a minor', while 31.2% had seen
      tobacco products being sold 'by a minor'. In addition, 24.8% had 'very often'
      seen tobacco products being sold within a radius of 100 yards of educational
      institutions.

PMID- 23167394
TI  - Lung cancer in Malabar Cancer Center in Kerala--a descriptive analysis.
AB  - The burden of lung cancer in terms of mortality is the highest among all types of
      cancers globally. The present study aimed to evaluate lifestyle related habits,
      clinico-pathological profile and treatment details of lung cancer patients who
      were registered at Malabar Cancer Centre (MCC), Kerala, during the calendar year
      2010. A retrospective evaluation was made from medical records to gather data
      from 281 registered lung cancer cases in 241 males and 40 females, with a male to
      female ratio of 6.03: 1. Approximately 89% of the cases were above 50 years of
      age. Among males about 91% of the cases were smokers and 62% of them had a
      chronic smoking habit. Adenocarcinomas, squamous cell carcinomas, non-small cell
      carcinomas and small cell cancers accounted for 10.7, 13.9, 17.0 and 5.7%
      respectively. Out of 281 cases around 67% were diagnosed with distant metastasis
      and the remainder had regional lymph node involvement. However, no statistically
      significant difference was observed for secondary site of tumor according to
      gender. As majority of the cases reported at MCC were in an advanced stage of the
      disease, histology of the secondary site from supraclavicular lymph nodes or
      liver was taken for diagnosis. Initiation of population based screening for early
      detection of cancer, and primary and secondary prevention strategies for reducing
      the prevalence of tobacco consumption are high priorities to reduce the lung
      cancer burden in Kerala.

PMID- 23167395
TI  - Metaplastic breast carcinoma: case series and review of the literature.
AB  - Metaplastic breast carcinoma (MpBC) is a rare disease entity, accounting for less
      than 1% of all breast carcinomas. Furthermore, it is a heterogenous disease with
      different subgroups, including malignant epithelial (carcinoma) and stromal
      (sarcoma) features. Here we evaluated, retrospectively, 14 female MpBC patients
      admitted to Ankara Oncology Training and Research Hospital between 2005 and 2011.
      Median age was 45.5 (range:16.0-76.0) and tumor size 57.5 mm (range: 20.0-80.0
      mm). Histopathological subtypes were as follows: 5 carcinosarcoma, 5 squamous and
      4 adenosquamous carcinoma. All but one with upfront lung metastasis, had their
      primary breast tumor operated. Axillary lymph nodes were involved in 64.3%. The
      most common sites of metastasis were lungs and brain. Chemotherapy including
      antracycline, taxane and even platinium was planned for adjuvant, neoadjuvant and
      palliative purposes in 9, 3 and 1 patient, respectively. Median cycles of
      chemotherapy was 6 (range:4-8). Median follow-up of the patients was 52 months
      (95%CI 10.4-93.6 month). Median 3 year progression free survival (PFS) and
      overall survival (OS) in this patients cohort were 33% and 56%, respectively. In
      conclusion, MpBC is a rare and orphan disease without standardized treatment
      approaches and the prognosis is poor so that larger studies to investigate
      different treatment schedules are urgently needed.

PMID- 23167396
TI  - Does the success of a school-based HPV vaccine programme depend on teachers'
      knowledge and religion? -- A survey in a multicultural society.
AB  - Organized introduction of prophylactic human papillomavirus (HPV) vaccination can
      reduce the burden of cervical cancer in developing countries. One of the most
      effective ways is through a national school-based program. Information on
      teachers is therefore important since this group may have a disproportionate
      influence in the success of any implementation. OBJECTIVE: To assess teachers'
      knowledge and perception of HPV, cervical cancer and HPV vaccine prior to
      commencing a school-based HPV vaccination program in a multiethnic, predominantly
      Muslim country. Factors associated with acceptability of the vaccine were
      identified. METHOD: A bilingual questionnaire was applied to 1,500 secondary
      school teachers from 20 urban schools in Malaysia. Data collected were analyzed
      using SPSS version 17. RESULTS: 1,166 questionnaires were returned. From this
      group, 46.1% had never heard of HPV while 50.9% had never had a pap smear.
      However, 73.8% have heard of the HPV vaccine with 75% agreeing to have it. 96%
      considered themselves religious with 79.8% agreeing to have the vaccine.
      CONCLUSIONS: A national school-based HPV immunization program can be implemented
      effectively in a multiethnic, cultural and religious country despite limited
      knowledge of HPV-related pathology among teachers. In addition, the perception
      that religion has a negative influence on such a program is unwarranted.

PMID- 23167397
TI  - Inhibitory effects of Opuntia humifusa on 7, 12-dimethyl- benz[a]anthracene and
      12-O-tetradecanoylphorbol-13- acetate induced two-stage skin carcinogenesis.
AB  - Opuntia humifusa, member of the Cactaceae family, was previously demonstrated to
      have radical scavenging, anti-inflammatory and anti-proliferative effects in in
      vitro models. It was suggested that O. humifusa could function in the prevention
      of carcinogenesis. To investigate the in vivo chemopreventive effect of O.
      humifusa, mice were fed a diet containing either 1% or 3% following 7, 12
      dimethylbenz[a] anthracene (DMBA) and 12-O-tetradecanoylphorbol-13-acetate (TPA)
      induction of skin carcinogenesis. Significant decrease in the numbers of
      papilloma and epidermal hyperplasia were observed in mice fed with O. humifusa,
      compared to the control group. O. humifusa also upregulated high total
      antioxidant capacity and level of phase II detoxifying enzyme such as superoxide
      dismutase and glutathione S-transferase activity in the skin. Lipid peroxidation
      activity level was measured in skin cytosol and significantly inhibited in 3% OH
      fed group compared to the control group. These results suggest that O. humifusa
      exerts chemopreventive effects on chemical carcinogenesis in mouse skin and that
      prevention effects are associated with reduction of oxidative stress via the
      modulation of cutaneous lipid peroxidation, enhancing of total antioxidant
      capacity especially in phase II detoxifying enzyme system and partial apoptotic
      influence.

PMID- 23167398
TI  - Development of a sampling strategy and sample size calculation to estimate the
      distribution of mammographic breast density in Korean women.
AB  - Mammographic breast density is a known risk factor for breast cancer. To conduct
      a survey to estimate the distribution of mammographic breast density in Korean
      women, appropriate sampling strategies for representative and efficient sampling
      design were evaluated through simulation. Using the target population from the
      National Cancer Screening Programme (NCSP) for breast cancer in 2009, we verified
      the distribution estimate by repeating the simulation 1,000 times using
      stratified random sampling to investigate the distribution of breast density of
      1,340,362 women. According to the simulation results, using a sampling design
      stratifying the nation into three groups (metropolitan, urban, and rural), with a
      total sample size of 4,000, we estimated the distribution of breast density in
      Korean women at a level of 0.01% tolerance. Based on the results of our study, a
      nationwide survey for estimating the distribution of mammographic breast density
      among Korean women can be conducted efficiently.

PMID- 23167399
TI  - First trial of cervical cytology in healthy women of urban Laos using by self
      sampling instrument.
AB  - Cervical cancer is the most common cancer in Laos women and a screening
      programme, even with the PAP smear test (PAP test), has yet to be established for
      routine use. The Pap test is accepted as the most appropriate for cervical cancer
      screening in some settings but it is not commonly available in Laos hospitals,
      because there are few cytopathologists and gynecologists have little experience.
      As a pilot program, seminars for the PAP test were given in 2007 and 2008, and
      then PAP tests were carried out using self-sampling instrument (Kato's device)
      with 200 healthy volunteers in Setthathirath hospital, Laos, in 2008. The actual
      examination number was 196, divided into class I 104 (53.1%), class II 85
      (43.3%), class IIIa 4 (2.0%), class IIIb 1 (0.5%), and class V 1 (0.5%) by
      modified Papanicolau classification. Four cases had menstruation. There were 6
      cases with epithelial cell abnormalities including malignancy. There were 7 cases
      with fungus and 2 cases with trichomonas in Class II. More than 70% volunteers
      felt comfortable with the Kato's device and wanted to use it next time, because
      of the avoidance of the embarrassment and a low cost as compared with pelvic
      examination by gynecologists. This first trial for PAP test for healthy Laos
      women related to a hospital found three percent to have abnormal cervical
      epithelial cells. Therefore, this appraoch using a self-sampling device suggests
      that it should be planned for cervical cancer prevention in Laos.

PMID- 23167401
TI  - No association between egg intake and prostate cancer risk: a meta-analysis.
AB  - OBJECTIVE: Egg consumption has been suggested to increase the risk of colorectal
      and some other cancers. The present study summarized and quantified the current
      evidence relating dietary intake of eggs and prostate cancer. MATERIALS AND
      METHODS: Literature searches were conducted to identify peer-reviewed manuscripts
      published up to July 2012. Twenty manuscripts from nine cohort studies and 11
      case-control studies were identified. Summary risk estimates with 95% confidence
      intervals (CIs) were calculated for case-control and cohort studies separately.
      RESULTS: Neither the case-control not the cohort studies showed any association
      of prostate cancer incidence with egg consumption (case-control studies: odds
      ratio 1.09, 95% CI 0.86-1.31; cohort studies: relative risk 0.97, 95% CI 0.97
      1.07). The results were consistent in subgroup analysis. Furthermore, no
      association was observed between egg consumption and prostate cancer-specific
      mortality. CONCLUSIONS: Our analyses provided no evidence of a significant
      influence of egg consumption on prostate cancer incidence and mortality. However,
      more studies, particularly large prospective studies, are needed.

PMID- 23167400
TI  - Safety assessment of ovarian cryopreservation and transplantation in nude mice
      bearing human epithelial ovarian cancer.
AB  - OBJECTIVE: Nude mice with orthotopic transplantation of human ovarian epithelial
      cancer were used to investigate screening criteria for paraneoplastic normal
      ovarian tissue and the security of the freezing and thawing for ovarian tissue
      transplantation. METHODS: Expression of CK-7, CA125, P53, survivin, MMP-2/TIMP- 2
      in paraneoplastic normal ovarian tissues were detected by RT-PCR as well as
      immunohistochemistry. The tissues of the groups with all negative indicators of
      RT-PCR, all negative indicators of immunohistochemistry, negative expression of
      CK-7, CA125 and survivin, positive expression of CK-7, CA125 and survivin, cancer
      tissues and normal ovarian tissues of nude mice were used for freezing and
      thawing transplantation, to analyze overt and occult carcinogenesis rates after
      transplantation. RESULTS: When all indicators or the main indicators, CK-7, CA125
      and survivin, were negative, tumorigenesis did not occur after transplantation.
      In addition the occult carcinogenesis rate was lower than in the group with
      positive expression of CK-7, CA125 and survivin (P<0.01). After subcutaneous and
      orthotopic transplantation of ovarian tissues, rates did not change (P>0.05).
      There was no statistical significance among rates after transplantation of
      ovarian tissues which were obtained under different severity conditions (P>0.05).
      CONCLUSION: Negative expression of CK-7, CA125 and survivin can be treated as
      screening criteria for security of ovarian tissues for transplantation.
      Immunohistochemical methods can be used as the primary detection approach. Both
      subcutaneous and orthotopic transplantation are safe. The initial severity does
      not affect the carcinogenesis rate after tissue transplantation. Freezing and
      thawing ovarian tissue transplantation in nude mice with human epithelial ovarian
      carcinoma is feasible and safe.

PMID- 23167402
TI  - Transforming growth factor beta-1 C-509T polymorphism and cancer risk: a meta
      analysis of 55 case-control studies.
AB  - AIM: To investigate the association of transforming growth factor-beta 1 (TGF
      beta1) C-509T polymorphism and susceptibility to cancer by means of meta
      analysis. METHODS: An extensive search was performed to identify eligible case
      control studies investigating such a link. The strength of the association
      between TGF-beta1 C-509T polymorphism and cancer risk was assessed by pooled odds
      ratios (ORs) and 95%confidence intervals (95%CIs) in fixed or random effects
      models. RESULTS: 55 published case-control studies with a total number of 21,639
      cases and 28,460 controls were included. Overall, there was no association
      between TGF-beta1 C-509T and cancer risk in all genetic comparison models (TT vs.
      CC: OR=1.01, 95%CI=0.89-1.15; T vs. C: OR=1.01, 95%CI=0.94-1.07). However, a
      stratified analysis by cancer type indicated -509 T allele was significantly
      associated with decreased risk of colorectal cancer (CRC) (TT vs. CT/CC: OR=0.85,
      95%CI=0.76-0.95), especially for Caucasians (TT vs. CT/CC: OR=0.83, 95%CI=0.71
      0.98) and for population-based studies (TT vs. CT/CC: OR=0.78, 95%CI=0.68- 0.89).
      CONCLUSION: This meta-analysis suggested that TGF-beta1 C-509T polymorphism might
      contribute to a decreased risk on colorectal cancer susceptibility, especially
      for Caucasians.

PMID- 23167403
TI  - Genetic variation in PDCD6 and susceptibility to lung cancer.
AB  - Lung cancer is the most common type of cancer and one of the leading causes of
      death in the world. Genetic factors play an important role in its development.
      PDCD6, the encoding gene for programmed cell death protein 6, may function as a
      tumor suppressor gene. Non-small cell lung cancer (NSCLC) contributes about 80%
      to newly histologically diagnosed lung cancer patients. To explore the
      relationship between PDCD6 and NSCLC, we examined two single nucleotide
      polymorphisms(rs3756712 G/T andrs4957014 G/T, both in the intron region) of the
      PDCD6gene.A hospital-based case-control study was carried out including 302
      unrelated NSCLC patients and 306 healthy unrelated subjects. Significantly
      increased NSCLC risk was found to be associated with the T allele of rs4957014
      (P=0.027, OR=0.760, 95%CI=0.596-0.970). The genotype and allele frequencies of
      rs3756712 did not shown any significant difference between NSCLC group and
      controls (P=0.327, OR=0.879, 95%CI=0.679- 1.137). In conclusion, we firstly
      demonstrated the association between the PDCD6 gene and risk of NSCLC in a
      Chinese Han population.

PMID- 23167404
TI  - Urinary concentrations of human epidydimis secretory protein 4 (He4) in the
      diagnosis of ovarian cancer: a case--control study.
AB  - OBJECTIVE: To analyze differential diagnostic accuracy of urinary human
      epidydimis secretory protein 4 (HE4) in patients with ovarian tumors. MATERIALS
      AND METHODS: In the case-control study 23 patients with ovarian cancer, 37
      patients with benign ovarian tumors and 18 women in the control group were
      included. Serum CA125 values and urinary concentrations of HE4were assessed
      quantitatively. Urinary creatinine concentrations and glomerular filtration rate
      were also determined and used to calculate ratios to HE4. RESULTS: Higher urinary
      HE4 concentrations were observed in patients with late stage ovarian cancer
      (p=0.001) and also in patients with early stage ovarian cancer when compared to
      patients with benign ovarian tumors (p=0.044). On analysis where all ovarian
      cancer patients were included, higher diagnostic accuracy was observed with
      calculated ratio of HE4 to glomerular filtration rate (GFR) to unchanged urinary
      HE4 concentrations -AUC 0.861 vs. 0.858. When discriminatory accuracy was
      calculated for urinary HE4/GFR ratio and unchanged urinary HE4 concentrations,
      the last demonstrated a higher area under the curve - 0.701 vs. 0.602. The
      urinary HE4/creatinine ratio had lower discriminatory characteristics than
      unchanged concentrations of urinary HE4. However, HE4 serum concentration was
      more accurate for discrimination of patients with benign and malignant ovarian
      tumors when compared to urinary HE4 and CA125 in sera (AUCs were 0.868 for serum
      HE4 and 0.856 and 0.653 for urinary HE4 and CA125, respectively). CONCLUSIONS:
      Ovarian cancer patients have higher urinary concentrations of human epidydimis
      secretory protein 4 than patients with benign ovarian tumors. Urinary HE4 has
      comparable discriminatory accuracy with serum HE4 for benign and malignant
      ovarian tumors and can be recommended as a non-invasive ovarian cancer risk
      assessment method.

PMID- 23167405
TI  - Effect of portal vein chemotherapy on liver metastasis after surgical resection
      of colorectal cancer.
AB  - OBJECTIVE: To explore the effect of portal vein chemotherapy on liver metastasis
      after surgical resection of colorectal cancer. METHODS: Patients fulfilling the
      eligibility criteria were assigned to receive either surgery plus 1-week
      continuous infusion of 5-FU (study group) or surgery alone (observational group).
      Patients in the study group received portal vein chemotherapy, whereby 5-FU (1000
      mg/d) and heparin (5000 IU/d) infusion was initiated from the day of surgery and
      lasted for 7 consecutive days. Liver metastasis was monitored during five years
      follow-up postoperatively. RESULTS: Sixty four patients were recruited and
      assigned to the study group (12 with colon and 20 with rectal cancer) or the
      control group (10 with colon and 22 with rectal cancer). Liver metastasis rate
      was 12.5% in study and 25.0% in observational group, the difference being
      significant (P<0.01). CONCLUSION: Portal vein chemotherapy could be an effective
      treatment in preventing liver metastasis after surgical resection of colorectal
      cancer.

PMID- 23167406
TI  - Comparison of vinorelbine, ifosfamide and cisplatin (NIP) and etoposide and
      cisplatin (EP) for treatment of advanced combined small cell lung cancer (cSCLC)
      patients: a retrospective study.
AB  - OBJECTIVE: To compare efficacy and safety profile of vinorelbine, ifosfamide and
      cisplatin (NIP) with etoposide and cisplatin (EP) in the treatment of advanced
      combined small cell lung cancer (c-SCLC). METHODS: From January 2006 to December
      2010, 176 patients with advanced c-SCLC were enrolled. The primary endpoint was
      overall survival (OS) and the secondary endpoints were progression free survival
      (PFS), response rate (RR) and toxicity. RESULTS: Overall RR was 30.0% in the NIP
      and 38.5% in the EP group; there was no significant difference (P=0.236). The PFS
      in the EP group was little longer than that of NIP group, with 6.5 months for EP
      and 6.0 months for NIP group, but the difference was statistically non
      significant (P=0.163). The median OS and one year survival rates were 10.4 months
      and 36.3% for NIP group, and 10.8 months and 49.0% for EP respectively, EP
      showing a survival benefit, although this was not statistically significant. Both
      groups well tolerated the adverse effects. The incidence of grade I-II leucopenia
      and alopecia in the NIP group was significantly higher than that of EP group
      (32.5% vs. 10.4% (P<0.001, 35.0% vs. 12.5%, P<0.001). CONCLUSION: the ORR, PFS
      and OS in NIP were slightly inferior to traditional regimen EP. The toxicity of
      NIP can be considered tolerable. The usage of three drugs combination in the
      treatment of mixed SCLC remains uncertain. Nevertheless, the results need to be
      further confirmed by large, prospective clinical trials.

PMID- 23167407
TI  - Prognostic significance of annexin A1 expression in pancreatic ductal
      adenocarcinoma.
AB  - Annexin A1 is a 37-kDa calcium- and phospholipid-binding protein of the annexin
      superfamily considered to play an important role in tumorigenesis. However,
      associations with clinicopathological features in pancreatic ductal
      adenocarcinoma (PDAC) cases have yet to be fully defined. We therefore
      investigated the prognostic value of annexin A1 protein as a PDAC biomarker in 83
      tumor and matched non-cancerous tissues or normal pancreas tissues. Expression
      was analyzed using real-time RT-PCR, Western blotting and immunohistochemistry.
      In non-tumor tissue, myoepithelial cells showed no or weak expression of annexin
      A1 while expression was strong and sometimes even located in the nuclei of
      endothelial cells in tumor tissue. High expression was significantly associated
      with advanced stage (P <0.05) and a worse overall survival (P <0.05). These
      results provide new insights to better understand the role of annexin A1 in PDAC
      survival, and might be relevant to prediction of prognosis and development of
      more effective therapeutic strategies aimed at improving survival.

PMID- 23167408
TI  - Dietary patterns and risk of colorectal cancer: a systematic review of cohort
      studies (2000-2011).
AB  - OBJECTIVES: This systematic review of cohort studies aimed to identify any
      association between specific dietary patterns and risk of colorectal cancer
      (CRC). Dietary patterns involve complex interactions of food and nutrients
      summarizing the total diet or key aspects of the diet for a population under
      study. METHODS AND MATERIALS: This review involves 6 cohort studies of dietary
      patterns and their association with colorectal cancer. An exploratory or a
      posteriori approach and a hypothesis-oriented or a priori approach were employed
      to identify dietary patterns. RESULTS: The dietary pattern identified to be
      protective against CRC was healthy, prudent, fruits and vegetables, fat
      reduced/diet foods, vegetables/fish/poultry, fruit/wholegrain/dairy, healthy
      eating index 2005, alternate healthy eating index, Mediterranean score and
      recommended food score. An elevated risk of CRC was associated with Western diet,
      pork processed meat, potatoes, traditional meat eating, and refined grain
      pattern. CONCLUSION: The Western dietary pattern which mainly consists of red and
      processed meat and refined grains is associated with an elevated risk of
      development of CRC. Protective factors against CRC include a healthy or prudent
      diet, consisting of vegetables, fruits, fish and poultry.

PMID- 23167409
TI  - Factors associated with cervical cancer screening amongst women of reproductive
      age from Yucatan, Mexico.
AB  - This study aimed to analyse the participation of women of reproductive age in a
      cancer screening program, and survey reasons for non-screening in a region from
      Mexico with high cervical cancer mortality. A total of 281 obstetric patients
      from a previous HPV study in a social security hospital during 2008-2009 were
      included. Reasons for not participating in the screening were directly asked. HPV
      positive patients were invited to participate in an informative workshop, and
      they filled in a knowledge questionnaire. The women ranged in age from 14-47
      years; 123 (43.8%) had never participated in screening, of which 97 (78.9%) had
      their first sexual intercourse 2 to 10 years ago, resulting in 25% HPV positive.
      Screening history was strongly associated with 2 or more gestations (OR= 10.07,
      p=0.00) and older age (OR=6.69 p=0.00). When 197 women were contacted and
      interviewed, reasons referred for non-screening were ignorance, lack of interest
      or time, recent sexual onset, shame and fear. More than 50% of the workshop
      participants showed knowledge of HPV, while 38.9% and 25% knew about Pap smear
      and cervical cancer. A high percentage of women of reproductive age have never
      had a Pap smear. Promoting the screening program in medical facilities seems to
      be important in this population. New approaches to inform vulnerable individuals
      on the benefits of screening need to be implemented, especially for young women.

PMID- 23167410
TI  - Genetic polymorphism of glutathione S-transferases M1 and T1, tobacco habits and
      risk of stomach cancer in Mizoram, India.
AB  - AIM: The incidence of stomach cancer in Mizoram is highest in India. We have
      conducted a population based matched case-control study to identify environmental
      and genetic risk factors in this geographical area. METHODS: A total of 102
      histologically confirmed stomach cancer cases and 204 matched healthy population
      controls were recruited. GSTM1 and GSTT1 genotypes were determined by PCR and H.
      pylori infections were determined by ELISA. RESULTS: Tobacco-smoking was found to
      be an important risk factor for high incidence of stomach cancer in Mizoram.
      Meiziol (local cigarette) smoking was a more important risk factor than other
      tobacco related habits. Cigarette, tuibur (tobacco smoke infused water) and betel
      nut consumption synergistically increased the risk of stomach cancer.
      Polymorphisms of GSTM1 and GSTT1 genes were not found to be directly associated
      with stomach cancer in Mizoram. However, they appeared to be effect modifiers.
      Persons habituated with tobacco smoking and/or tuibur habit had increased risk of
      stomach cancer if they carried the GSTM1 null genotype and GSTT1 non-null
      genotype. CONCLUSION: Tobacco smoking, especially meiziol is the important risk
      factor for stomach cancer in Mizoram. GSTM1 and GSTT1 genes modify the effect of
      tobacco habits. This study is a first step in understanding the epidemiology of
      stomach cancer in Mizoram, India.

PMID- 23167411
TI  - Tobacco-related chronic illnesses: a public health concern for Jamaica.
AB  - BACKGROUND: Tobacco use is a leading cause of preventable morbidity and mortality
      from non-communicable diseases. The objectives of the study were to determine the
      percentage of annual income used to purchase tobacco-related products and treat
      tobacco-related illnesses, and assess the characteristics of smokers and their
      awareness of the health-related risks of smoking. METHOD: Stratified and snowball
      sampling methods were used to obtain information (via a 17-item, close-ended
      questionnaire) from 85 adult respondents (49 males and 36 females). The
      instrument comprised of demographic characteristics, smoking
      behavioural/lifestyle, health, and micro socio-economics. RESULTS: There were no
      significant differences between individuals who were affected by chronic
      obstructive pulmonary disorder (COPD) (14.1%) and cardiovascular disease (18.8%).
      It was found that respondents spend 30-39% of their annual income on tobacco
      related products. Forty percent (40.0%) and 41.7% of respondents with lung cancer
      and COPD respectively spend more than 50% of their annual income to treat these
      diseases. The majority (80%) of those who continues to consume tobacco-related
      products were uncertain as to why they were doing it. Not all the smokers were
      aware of the dangers of tobacco consumption despite their level of education.
      CONCLUSION: The majority of the respondents who had tobacco-related illnesses
      such as lung cancer and COPD spend a significant amount of their income on their
      health care. Not all the smokers were aware of the dangers of tobacco consumption
      despite their level of education. This suggests the need for increase public
      awareness where both smokers and non smokers are being fully or adequately
      informed about the dangers or health risks of tobacco consumption.

PMID- 23167412
TI  - Involvement of FoxM1 in non-small cell lung cancer recurrence.
AB  - BACKGROUND: Predictive biomarkers for lung cancer recurrence after curative tumor
      resection remain unclear. This study set out to assess the role of FoxM1 in the
      recurrence of non-small cell lung cancer. METHODS: Immunohistochemistry for FoxM1
      expression was performed on paraffin-embedded tumor tissues from 165 NSCLC
      patients. Association of FoxM1 expression with clinicopathological parameters and
      disease free survival were evaluated. RESULTS: Our results indicated FoxM1
      expression to be significantly associated with poorer tissue differentiation (P
      =0.03), higher TNM stage (P <0.01), lymph node metastasis (P <0.01), advanced
      tumor stage (P <0.01), and poorer disease free survival (P <0.01). Multivariable
      analysis showed that FoxM1 expression increased the hazard of recurrence (hazard
      ratio= 1.96, 95% CI, 1.04-3.17, P <0.05), indicating that FoxM1 is an independent
      and significant predictor of lung cancer recurrence. CONCLUSION: Therefore, FoxM1
      is an independent risk factor for recurrence of NSCLC. Elevated FoxM1 expression
      could be used as an indicator of poor disease free survival.

PMID- 23167413
TI  - Diagnostic value of fluorescence in situ hybridization assay in malignant
      mesothelioma: a meta-analysis.
AB  - The diagnosis of malignant mesothelioma (MM) remains a clinical challenge and the
      fluorescence in situ hybridization (FISH) assay has been reported to be one
      promising tool. The present meta-analysis aimed to establish the overall
      diagnostic accuracy of FISH for diagnosing MM. After a systematic review of
      English language studies, the sensitivity, specificity and other measures of
      accuracy of FISH in the diagnosis of MM were pooled using random-effects models.
      Summary receiver operating characteristic curves were applied to summarize
      overall test performance. Nine studies met our inclusion criteria, the pooled
      sensitivity and specificity for FISH for diagnosing MM being 0.72 (95% CI 0.67
      0.76) and 1.00 (95% CI 0.98-1.00), respectively. The positive likelihood ratio
      was 34.5 (95% CI 14.5-82.10), the negative likelihood ratio was 0.24 (95% CI 0.16
      0.36), and the diagnostic odds ratio was 204.9 (95% CI 76.8-546.6), the area
      under the curve being 0.99. Our data suggest that the FISH assay is likely to be
      a useful diagnostic tool for confirming MM. However, considering the limited
      studies and patients included, further large scale studies are needed to confirm
      these findings.

PMID- 23167414
TI  - Combined EGFR and c-Src antisense oligodeoxynucleotides encapsulated with PAMAM
      Denderimers inhibit HT-29 colon cancer cell proliferation.
AB  - Colon cancer continues to be one of the most common cancers, and the importance
      and necessity of new therapies needs to be stressed. The most important proto
      oncogen factors for colon cancer appear to be epidermal growth factor receptor,
      EGFR, and c-Src with high expression and activity leading to tumor growth and
      ultimately to colon cancer progression. Application of c-Src and EGFR antisense
      agents simultaneously should theoretically therefore have major benefit. In the
      present study, anti-EGFR and c-Src specific antisense oligodeoxynucleotides were
      combined in a formulation using PAMAM dendrimers as a carrier. Nano drug entry
      into cells was confirmed by flow cytometry and fluorescence microscopy imaging
      and real time PCR showed gene expression of c-Src and EGFR, as well as downstream
      STAT5 and MAPK-1 with the tumor suppressor gene P53 to all be downregulated. EGFR
      and c-Src protein expression was also reduced when assessed by western blotting
      techniques. The effect of the antisense oligonucleotide on HT29 cell
      proliferation was determined by MTT assay, reduction beijng observed after 48
      hours. In summary, nano-drug, anti-EGFR and c-Src specific antisense
      oligodeoxynucleotides were effectively transferred into HT-29 cells and inhibited
      gene expression in target cells. Based on the results of this study it appears
      that the use of antisense EGFR and c-Src simultaneously might have a significant
      effect on colon cancer growth by down regulation of EGFR and its downstream
      genes.

PMID- 23167415
TI  - Impact of low versus conventional doses of chemotherapy during transcatheter
      arterial chemo-embolization on serum fibrosis indicators and survival of liver
      cancer patients.
AB  - OBJECTIVES: To explore the impact of low- vs conventional-dose chemotherapy via
      transcatheter arterial chemo-embolization (TACE) on serum fibrosis indicators and
      treatment efficacy of hepatocellular cancer patients (HCC). MATERIALS AND
      METHODS: Patients fulfilling the eligibility criteria were assigned to TACE in
      Group A (with low-dose chemotherapy) or Group B (conventional-dose chemotherapy).
      Four serum fibrosis related indicators, hyaluronic acid(HA), human pro-collagen
      type-III (hPC-III), laminin (LN), and collagen type-IV(IV-C) before TACE were
      compared with the values 7 days after TACE. The response rate and survival time
      were also compared between the two groups. RESULTS: Fifty patients with HCC were
      enrolled in this study, including 25 in Group A and 25 in Group B. No significant
      differences were detected between the two groups in the four indicators before
      TACE. After TACE, the value of the four serum indicators increased significantly
      in Group B. However, no significant differences regarding these four indicators
      were found in Group A after TACE. Significant differences were demonstrated
      between the two groups after TACE, but median survival time and 1 or 2 year
      overall survival rates did not differ (P>0.05). CONCLUSIONS: Low-, compared with
      conventional-dose chemotherapy exerts the same impact on the variation of
      fibrosis related indicators and has no influence on median survival time and
      survival rate after TACE in HCC patients.

PMID- 23167416
TI  - Toll-like receptor 5 agonism protects mice from radiation pneumonitis and
      pulmonary fibrosis.
AB  - Radiation pneumonitis and pulmonary fibrosis are the main complications with
      radiotherapy for thoracic neoplasms, directly limiting the efficient dose in
      clinical application and currently there are few medicines that effectively
      function as radioprotectants. However, a TLR5 agonist, CBLB502, was confirmed to
      have protective efficacy against hematopoietic and gastrointestinal radiation
      syndromes in mice and primates. This study points to a new direction for
      protection against thoracic radiation-induced pulmonary syndromes and skin injury
      by CBLB502. We utilized the TUNEL assay, pathological analysis and
      immunohistochemistry to obtain evidence that CBLB502 could alleviate the
      occurrence of radiation pneumonitis and pulmonary fibrosis as well as radiation-
      induced skin injury. It may thus play a promising role in facilitating clinical
      radiotherapy of thoracic neoplasms.

PMID- 23167417
TI  - Healthy lifestyle changes during the period before and after cancer diagnosis
      among breast cancer survivors.
AB  - AIMS: The purpose of the present study was to investigate healthy lifestyle
      changes during the period before and after breast cancer diagnosis in Taiwan.
      MATERIALS AND METHOD: Lifestyle changes during the period before and after cancer
      diagnosis were assessed by convenience sampling with a structured questionnaire
      for breast cancer survivors. RESULTS: A total of 235 breast cancer survivors
      completed the healthy lifestyle scale. The mean values before and after breast
      cancer diagnosis of the participants were 3.27 and 3.73. The final five
      dimensions for the period before breast cancer diagnosis were: had not
      experienced stress; had exercised; had maintained sleep quality; had maintained
      body weight; and had maintained relationships. The final five dimensions for the
      period after breast cancer diagnosis were: sleep quality; had not experienced
      stress; relationship; had exercised; and had maintained body weight. A paired-t
      test was applied to examine the differences before and after cancer diagnosis,
      revealing that the total average scores of the participants on the healthy
      lifestyle scale clearly differed statistically (t= -17.20, p<0.01); and the nine
      dimensions before and after testing also demonstrate a marked statistical
      difference (p<0.01). CONCLUSIONS: These findings are helpful in understanding the
      healthy lifestyle changes during the period before and after cancer diagnosis
      among breast cancer survivors. It is expected that these results can offer
      references of self-care for this group of patients.

PMID- 23167418
TI  - Clinical study on safety and efficacy of Qinin(r) (cantharidin sodium) injection
      combined with chemotherapy in treating patients with gastric cancer.
AB  - OBJECTIVES: To assess the efficacy, side effects, and the impact on quality of
      life with Qinin(r) (Cantharidin sodium) injection combined with chemotherapy for
      gastric cancer patients. METHOD: A consecutive cohort of 70 patients were divided
      into two groups: experimental group with cantharidin sodium injection combined
      with chemotherapy, while the control group received chemotherapy alone. After
      more than two courses of treatment, efficacy, quality of life and side effects
      were evaluated. RESULTS: The response rate of experimental group was not
      significantly different from that of the control group (P>0.05), but differences
      were significant in clinical benefit response and KPS score. In addition,
      gastrointestinal reactions and the incidence of leukopenia were lower than in the
      control group (P<0.05). CONCLUSIONS: Qinin(r) (Cantharidin sodium) injection
      combined with chemotherapy enhances clinical benefit response, improving quality
      of life of gastric cancer patients and reducing side effects of chemotherapy.
      Thus Qinin(r) (Cantharidin sodium) injection deserves to be further investigated
      in randomized control clinical trails.

PMID- 23167419
TI  - Clinical study of thalidomide combined with dexamethasone for the treatment of
      elderly patients with newly diagnosed multiple myeloma.
AB  - OBJECTIVE: To investigate the relationship between the efficacy and safety of
      different doses of thalidomide (Thal) plus dexamethasone (Dex) as the initial
      therapy in elderly patients with newly diagnosed multiple myeloma (MM). METHODS:
      Clinical data of 28 elderly patients with newly diagnosed MM who underwent the TD
      regimen as the initial therapy were analyzed retrospectively. The patients were
      divided into two groups according to the maximal sustained dose of Thal: lower
      dose (group A) and higher dose (group B). The overall response rate (ORR),
      progression free survival (PFS), overall survival (OS), and adverse events (AES)
      were compared between the two groups. RESULTS: A total of 28 patients were
      followed up with a median of 18 months. The ORR was 60.1%. The median response
      time and PFS were 2.0 and 17.0 months, respectively. The mean sustained dose of
      Thal in group B was significantly higher than group A (292.9 mg v 180.4 mg,
      P=0.01). There was no significantly difference in ORR (57.1% v 64.3%, P=1.00) and
      PFS (9.63months v 17.66 months, P=0.73) between groups A and B. During the follow
      up, only five patients died (<40%) and, therefore, median OS values were not
      available. It is estimated, however, that the mean survival time in the two
      groups was 35.6 and 33.4 months (P>0.05), respectively. All of the patients
      tolerated the treatment well. The incidence of AES in patients with a grading
      above 3 in group B was significantly higher than in group A (P=0.033).
      CONCLUSIONS: The TD regimen results in a high response rate and manageable AES as
      the initial therapy in elderly patients with MM. TD should be considered as the
      front line regimen for the treatment of elderly patients with MM in areas with
      financial constraints. The clinical response can be achieved at a low dose Thal
      with minimal toxicity.

PMID- 23167420
TI  - Association between XRCC1 gene polymorphisms and risk of glioma development: a
      meta-analysis.
AB  - OBJECTIVE: Previous studies of the association between X-ray cross-complementing
      group 1 (XRCC1) gene polymorphisms and the gliomas risk have yielded conflicting
      results, and thus a meta-analysis was performed to provide a more accurate
      estimation. METHODS: A computerized literature search of 5 electronic databases
      was conducted to identify the relevant studies. Fixed or random effect models
      were selected based on the heterogeneity test. Publication bias was estimated
      using Begg's funnel plots and Egger's regression test. RESULTS: A total of 11
      studies (3,810 cases and 6,079 controls), 7 studies (2,928 cases and 5,048
      controls), and 4 studies (1,461 cases and 2,593 controls) were finally included
      in the analyses of the association between XRCC1 Arg399Gln, Arg194Trp, and
      Arg280His polymorphisms and glioma risk, respectively. The pooled results showed
      that GlnGln carriage was associated with moderately increased risk of gliomas in
      Asians (GlnGln vs. ArgArg, OR=1.490, 95%CI 1.031-2.153; GlnGln/ArgGln vs. ArgArg,
      OR=1.321, 95%CI 1.037- 1.684), whereas a marginal association was revealed in
      Caucasians. For the Arg194Trp polymorphism, although a significant association
      was shown in the homozygous genotype comparisons (TrpTrp vs. ArgArg, OR = 2.209,
      95%CI 1.398- 2.945), no significant link was found on subgroup analysis
      stratified by ethnicity. With regard to the Arg280His polymorphism, no
      significant association was found in each comparison. No particular study was
      found to significantly influence the pooled results, and no potential publication
      bias was detected. CONCLUSIONS: This meta-analysis suggested that the XRCC1
      Arg399Gln polymorphism is moderately associated with increased risk of gliomas in
      Asians, while Arg194Trp and Arg280His polymorphisms demonstrated no significant
      influence. Due to the limited studies and the potential confounders, further
      studies are needed to confirm these results.

PMID- 23167421
TI  - Use of complementary and alternative medicine among breast cancer survivors in
      Taiwan.
AB  - AIMS: The purpose of this study was to investigate complementary and alternative
      medicine use among breast cancer survivors in Taiwan. MATERIALS AND METHODS: This
      study employed a descriptive research design approach to detail the CAM use among
      the target population. Convenience sampling was used along with a structured
      questionnaire. RESULTS: A total of 230 breast cancer survivors completed the use
      CAM scale. Prayer, reading books, taking antioxidants, eating various grains, and
      maintaining a vegetarian diet proved to be the five most frequently used CAM
      practices among patients in our study. More than 50.0% of the participants
      reported praying occasionally. More than 40.0% of participants read books
      occasionally, and 38.7% stated that they occasionally take antioxidants.
      CONCLUSIONS: These results provide more insight into CAM use for nurses who care
      for breast cancer patients.

PMID- 23167422
TI  - Microarray analysis of the hypoxia-induced gene expression profile in malignant
      C6 glioma cells.
AB  - Hypoxia is commonly featured during glioma growth and plays an important role in
      the processes underlying tumor progression to increasing malignancy. Here we
      compared the gene expression profiles of rat C6 malignant glioma cells under
      normoxic and hypoxic conditions by cDNA microarray analysis. Compared to normoxic
      culture conditions, 180 genes were up-regulated and 67 genes were down-regulated
      under hypoxia mimicked by CoCl2 treatment. These differentially expressed genes
      were involved in mutiple biological functions including development and
      differentiation, immune and stress response, metabolic process, and cellular
      physiological response. It was found that hypoxia significantly regulated genes
      involved in regulation of glycolysis and cell differentiation, as well as
      intracellular signalling pathways related to Notch and focal adhesion, which are
      closely associated with tumor malignant growth. These results should facilitate
      investigation of the role of hypoxia in the glioma development and exploration of
      therapeutic targets for inhibition of glioma growth.

PMID- 23167423
TI  - Health behavior after a multiprofessional intervention and training for ongoing
      volunteer-based community health programme intervention in the North-East of
      Thailand: what changed and what not?
AB  - This qualitative research within the project entitled "Multiprofessional
      Intervention and training for Ongoing Volunteer-based Community Health Programs
      in the Northeast of Thailand (MITV-NET) " was aimed at explaining changes of
      health behavior of community people in the Northeast after the intervention. The
      participants comprised 15 community volunteers and 27 villagers. Data were
      collected by indepth interview, focus group discussion, participation and non
      participation observation, and note taking. Analyses were conducted in parallel
      with data collection, through content and comparative analysis. It was found that
      the health behavior fell into 2 categories: easy-to-change and difficult-to
      change. The former involved fun activities joined by community people that
      improved their health or made them recover from illnesses after a short period
      without becoming addicted. These activities could be done by themselves, for
      example, exercising and cooking. The difficult-to- change health behavior is
      habitual, for example, chewing betel nuts or eating uncooked food. The following
      factors were found affecting behavioral changes: 1) underlying disease; 2)
      enjoyment in doing activities; 3) habitual behaviour; 4) improved health in a
      short period; 5) ability of community leaders and volunteers; and 6) community
      health-supporting resources. It is suggested that improving people's health
      requires cooperation of community people through fun activities and some initial
      external support. People who persist in bad habits should be encouraged to stop
      by showing them health deteriorating effects.

PMID- 23167424
TI  - Characterization and resistance mechanisms of a 5-fluorouracil- resistant
      hepatocellular carcinoma cell line.
AB  - PURPOSE: The chemoresistance of human hepatocellular carcinoma (HCC) to cytotoxic
      drugs, especially intrinsic or acquired multidrug resistance (MDR), still remains
      a major challenge in the management of HCC. In the present study, possible
      mechanisms involved in MDR of HCC were identified using a 5-fluorouracil (5-FU) 
      resistant human HCC cell line. METHODS: BEL-7402/5-FU cells were established
      through continuous culturing parental BEL-7402 cells, imitating the pattern of
      chemotherapy clinically. Growth curves and chemosensitivity to cytotoxic drugs
      were determined by MTT assay. Doubling times, colony formation and adherence
      rates were calculated after cell counting. Morphological alteration, karyotype
      morphology, and untrastructure were assessed under optical and electron
      microscopes. The distribution in the cell cycle and drug efflux pump activity
      were measured by flow cytometry. Furthermore, expression of potential genes
      involved in MDR of BEL-7402/5-FU cells were detected by immunocytochemistry.
      RESULTS: Compared to its parental cells, BEL-7402/5-FU cells had a prolonged
      doubling time, a lower mitotic index, colony efficiency and adhesive ability, and
      a decreased drug efflux pump activity. The resistant cells tended to grow in
      clusters and apparent changes of ultrastructures occurred. BEL-7402/5-FU cells
      presented with an increased proportion in S and G2/M phases with a concomitant
      decrease in G0/G1 phase. The MDR phenotype of BEL-7402/5-FU might be partly
      attributed to increased drug efflux pump activity via multidrug resistance
      protein 1 (MRP1), overexpression of thymidylate synthase (TS), resistance to
      apoptosis by augmentation of the Bcl-xl/Bax ratio, and intracellular adhesion
      medicated by E-cadherin (E-cad). P-glycoprotein (P-gp) might play a limited role
      in the MDR of BEL-7402/5-FU. CONCLUSION: Increased activity or expression of
      MRP1, Bcl-xl, TS, and E-cad appear to be involved in the MDR mechanism of BEL
      7402/5-FU.

PMID- 23167425
TI  - (-)-Epigallocatechin-3-gallate induces apoptosis and inhibits invasion and
      migration of human cervical cancer cells.
AB  - Invasion and metastasis are the major causes of cancer-related death.
      Pharmacological or therapeutic interventions such as chemoprevention of the
      progression stages of neoplastic development could result in substantial
      reduction in the incidence of cancer mortality. (-)-Epigallocatechin-3-gallate
      (EGCG), a promising chemopreventive agent, has attracted extensive interest for
      cancer therapy utilizing its antioxidant, anti- proliferative and inhibitory
      effects on angiogenesis and tumor cell invasion. In this study, we assessed the
      influence of EGCG on the proliferative potential of HeLa cells by cell viability
      assay and authenticated the results by nuclear morphological examination, DNA
      laddering assay and cell cycle analysis. Further we analyzed the anti-invasive
      properties of EGCG by wound migration assay and gene expression of MMP-9 and TIMP
      1 in HeLa cells. Our results indicated that EGCG induced growth inhibition of
      HeLa cells in a dose- and time- dependent manner. It was observed that cell death
      mediated by EGCG was through apoptosis. Interestingly, EGCG effectively inhibited
      invasion and migration of HeLa cells and modulated the expression of related
      genes (MMP-9 and TIMP-1) . These results indicate that EGCG may effectively
      suppress promotion and progression stages of cervical cancer development.

PMID- 23167426
TI  - Clinical predictive value of serum angiogenic factor in patients with
      osteosarcoma.
AB  - OBJECTIVE: To explore serum angiogenic factor expression in patients with
      osteosarcoma and its relationship with metastasis. METHODS: Immunohistochemistry
      was used to test the expression of CD34 and FVIII-Rag in osteosarcoma tissues of
      36 patients (osteosarcoma group) and microvessel density (MVD) was also recorded.
      In addition, ELISA was used to test the level of vascular endothelial growth
      factor (VEGF), basic fibroblast growth factor (bFGF), transforming growth factor
      beta1 (TGF-beta1) and endostatin (ES) in the osteosarcoma group and in a control
      group. RESULTS: VEGF and ES level were significantly higher than in the control
      group before operation (P<0.01), VEGF, bFGF and TGF-beta1 correlating with the ES
      level (P<.01). Serum VEGF and ES levels of osteosarcoma patients before surgery
      were closely related to relapse and metastasis; moreover, serum VEGF increased
      with MVD (P<0.01). Postoperative VEGF and ES levels were lower than the
      preoperation values (P<0.01); ES level in relapse group was significantly higher
      than that of the non-relapse group (P<0.01). CONCLUSION: Preoperative serum VEGF
      and postoperative ES levels have great predictive value with regard to relapse of
      osteosarcoma patients.

PMID- 23167427
TI  - Gelsolin induces promonocytic leukemia differentiation accompanied by
      upregulation of p21CIP1.
AB  - Tumor suppressor genes have received much attention for their roles in the
      development of human malignancies. Gelsolin has been found to be down-regulated
      in several types of human cancers, including leukemias. It is, however, expressed
      in macrophages, which are the final differentiation derivatives for the monocytic
      myeloid lineage, implicating this protein in the differentiation process of such
      cells. In order to investigate the role of gelsolin in leukaemic cell
      differentiation, stable clones over-expressing ectopic gelsolin, and a control
      clone were established from U937 leukaemia cells. Unlike the control cells, both
      gelsolin-overexpressing clones displayed retarded growth, improved monocytic
      morphology, increased NADPH and NSE activities, and enhanced surface expression
      of the beta-integrin receptor, CD11b, when compared with the parental U937 cells.
      Interestingly, RT- PCR and western blot analysis also revealed that gelsolin
      enhanced p21CIP1 mRNA and protein expression in the overexpressing clones.
      Moreover, transient transfection with siRNA silencing P21CIP1, but not the
      control siRNA, resulted in a reduction in monocytic differentiation, accompanied
      by an increase in proliferation. In conclusion, our work demonstrates that
      gelsolin, by itself, is capable of inducing monocytic differentiation in U937
      leukaemia cells, most probably through p21CIP1 activation.

PMID- 23167428
TI  - High dose rate Cobalt-60 after loading intracavitary therapy of the uterine
      cervical carcinoma in Srinagarind Hospital, analysis of residual disease.
AB  - OBJECTIVES: To evaluate residual disease in uterine cervical cancer patients
      treated with teletherapy using combined high dose rate Cobalt-60 brachytherapy.
      MATERIALS AND METHODS: A retrospective study of uterine cervical cancer patients,
      FIGO stages IB-IVB (International Federation of Gynecologists and Obstetricians
      recommendations), treated by radiotherapy alone between April 1986 and December
      1988 was conducted and the outcomes analysed. The patients were treated using
      teletherapy 50 Gy/25 fractions, five fractions per week to the whole pelvis
      together with HDR Cobalt -60 afterloading brachytherapy of 850 cGy/fraction,
      weekly to point A for 2 fractions. RESULTS: The study covered 141 patients with
      uterine cervical cancer. The mean age was 50.0 years with a range of 30-78 years.
      The mean tumor size was 4.1 cm in diameter (range 1-8 cm). Mean follow - up time
      was 2.94 years (range 1 month-6.92 years). The overall incidence of residual
      locoregional disease was 3.5%. Residual disease, according to stage IIB, IIIB and
      IVA was present in 2.78%, 3.37% and 50.0%. It was noted that there was no
      evidence of residual disease in stage IB and IIA cases. CONCLUSION: Combined
      teletherapy along with high dose rate Cobalt -60 brachytherapy of 850
      cGy/fraction, weekly to point A for 2 fractions resulted in overall 3.5% residual
      disease and a 96.5% complete response. The proposed recommendation for improving
      outcome is initiation of measurements for early detection of disease.

PMID- 23167429
TI  - Should male circumcision be advocated for genital cancer prevention?
AB  - The recent policy statement by the Cancer Council of Australia on infant
      circumcision and cancer prevention and the announcement that the quadrivalent
      human papillomavirus (HPV) vaccine will be made available for boys in Australia
      prompted us to provide an assessment of genital cancer prevention. While HPV
      vaccination of boys should help reduce anal cancer in homosexual men and cervical
      cancer in women, it will have little or no impact on penile or prostate cancer.
      Male circumcision can reduce cervical, penile and possibly prostate cancer.
      Promotion of both HPV vaccination and male circumcision will synergistically
      maximize genital cancer prevention.

PMID- 23167430
TI  - Spatial-temporal biphasic carcinogenesis--a new theory of the cancer system.
AB  - Cancer is now a worldwide problem. Although we have obtained a deeper
      understanding of the disease with the help of the science and technology, we
      still cannot reach the essence of cancer. Based on the former theory of
      carcinogenic and researches, we submit a new theory called "Spatial -Temporal
      Biphasic Carcinogenesis" to explain its development from the viewpoints of time
      and space.

PMID- 23167431
TI  - Chemotherapy through a combination of fasting and chronopharmacology.

PMID- 23167432
TI  - "The final piece of the puzzle to fit in": an interpretative phenomenological
      analysis of the return to employment in New Zealand after spinal cord injury.
AB  - PURPOSE: Little is known about employment experience after spinal cord injury
      (SCI) because most research to date concentrates on employment predictors. We
      explored the experiences of people with SCI, and vocational rehabilitation (VR)
      professionals working for a VR programme, in pursuing a return to employment in
      New Zealand (NZ) post-SCI. METHODS: Twelve people with SCI (four employed, three
      job-seeking, five unemployed) and six VR professionals were interviewed, and the
      transcripts subjected to an Interpretative Phenomenological Analysis. RESULTS:
      The core meaning of employment post-SCI was to live a normal life. Work
      advantages were social connectedness, a sense of self-worth, earning a living,
      and being occupied. Employment was the zenith of rehabilitation but not the first
      priority post-SCI. Employment barriers and facilitators were congruent with those
      found in similar studies. The role of VR was to sow the seeds of return to
      employment and to partner with the SCI client. CONCLUSIONS: For persons employed
      pre-SCI, we posit that employment identity modification is part of the return to
      employment process, alongside a supportive social context and networks, and
      adapted work environments. VR professionals may facilitate return to employment
      through understanding and fostering the process of employment identity
      modification and supporting clients to find work opportunities congruent with
      employment identity.

PMID- 23167433
TI  - UV-B impairs growth and gas exchange in grapevines grown in high altitude.
AB  - We previously demonstrated that solar ultraviolet-B (UV-B) radiation levels in
      high altitude vineyards improve berry quality in Vitis vinifera cv. Malbec, but
      also reduce berry size and yield, possibly as a consequence of increased
      oxidative damage and growth reductions (lower photosynthesis). The defense
      mechanisms toward UV-B signal and/or evoked damage promote production of
      antioxidant secondary metabolites instead of primary metabolites. Purportedly,
      the UV-B effects will depend on tissues developmental stage and interplay with
      other environmental conditions, especially stressful situations. In this work,
      grapevines were exposed to high solar UV-B (+UV-B) and reduced (by filtering) UV
      B (-UV-B) treatments during three consecutive seasons, and the effects of UV-B,
      developmental stages and seasons on the physiology were studied, i.e. growth,
      tissues morphology, photosynthesis, photoprotective pigments, proline content and
      antioxidant capacity of leaves. The +UV-B reduced photosynthesis and stomatal
      conductance, mainly through limitation in gas exchange, reducing plant's leaf
      area, net carbon fixation and growth. The +UV-B augmented leaf thickness, and
      also the amounts of photoprotective pigments and proline, thereby increasing the
      antioxidant capacity of leaves. The defense mechanisms triggered by + UV-B
      reduced lipid peroxidation, but they were insufficient to protect the
      photosynthetic pigments per leaf dry weight basis. The +UV-B effects depend on
      tissues developmental stage and interplay with other environmental conditions
      such as total radiation and air temperatures. 

PMID- 23167434
TI  - The effects of whey protein on cardiometabolic risk factors.
AB  - Obesity has reached epidemic proportions worldwide. The health consequences of
      obesity are more dangerous when associated with the metabolic syndrome and its
      components. Studies show that whey protein and its bioactive components can
      promote greater benefits compared to other protein sources such as egg and
      casein. The aim of this paper is to review the effects of whey protein on
      cardiometabolic risk factors. Using PubMed as the database, a review was
      conducted to identify current scientific literature on whey protein and the
      components of the metabolic syndrome published between 1970 and 2012. Consumption
      of whey protein seems to play an anti-obesity and muscle-protective role during
      dieting by increasing thermogenesis and maintaining lean mass. In addition, whey
      protein has been shown to improve glucose levels and insulin response, promote a
      reduction in blood pressure and arterial stiffness, and improve lipid profile.
      The collective view of current scientific literature indicates that the
      consumption of whey protein may have beneficial effects on some symptoms of the
      metabolic syndrome as well as a reduction in cardiovascular risk factors. 

PMID- 23167436
TI  - Transthoracic echocardiography for diagnosis of right pulmonary artery to left
      atrial fistula.
AB  - Right pulmonary artery to left atrial fistula (RPA-LAF) is a rare cardiovascular
      anomaly. There were no systematic and detail represent by echocardiography. We
      chose the patients who diagnosed with RPA-LAF at Fuwai Hospital from 2000 to
      2010. All patients underwent clinical examination, chest roentgenogram,
      laboratory testing, electrocardiography, transthoracic echocardiography (TTE),
      contrast echocardiography, and cardiac catheterization. In this article, we
      summarize the characteristics of the TTE for diagnosing the rare cardiovascular
      anomaly of RPA-LAF. We undertook a detailed review of their TTE and contrast
      echocardiography findings to determine the characteristic findings of this
      condition.

PMID- 23167435
TI  - ATPase active-site electrostatic interactions control the global conformation of
      the 100 kDa SecA translocase.
AB  - SecA is an intensively studied mechanoenzyme that uses ATP hydrolysis to drive
      processive extrusion of secreted proteins through a protein-conducting channel in
      the cytoplasmic membrane of eubacteria. The ATPase motor of SecA is strongly
      homologous to that in DEAD-box RNA helicases. It remains unclear how local
      chemical events in its ATPase active site control the overall conformation of an
      ~100 kDa multidomain enzyme and drive protein transport. In this paper, we use
      biophysical methods to establish that a single electrostatic charge in the ATPase
      active site controls the global conformation of SecA. The enzyme undergoes an ATP
      modulated endothermic conformational transition (ECT) believed to involve similar
      structural mechanics to the protein transport reaction. We have characterized the
      effects of an isosteric glutamate-to-glutamine mutation in the catalytic base, a
      mutation which mimics the immediate electrostatic consequences of ATP hydrolysis
      in the active site. Calorimetric studies demonstrate that this mutation
      facilitates the ECT in Escherichia coli SecA and triggers it completely in
      Bacillus subtilis SecA. Consistent with the substantial increase in entropy
      observed in the course of the ECT, hydrogen-deuterium exchange mass spectrometry
      demonstrates that it increases protein backbone dynamics in domain-domain
      interfaces at remote locations from the ATPase active site. The catalytic
      glutamate is one of ~250 charged amino acids in SecA, and yet neutralization of
      its side chain charge is sufficient to trigger a global order-disorder transition
      in this 100 kDa enzyme. The intricate network of structural interactions
      mediating this effect couples local electrostatic changes during ATP hydrolysis
      to global conformational and dynamic changes in SecA. This network forms the
      foundation of the allosteric mechanochemistry that efficiently harnesses the
      chemical energy stored in ATP to drive complex mechanical processes.

PMID- 23167437
TI  - Efficacy and safety of bendamustine for the treatment of patients with recurring
      Hodgkin lymphoma.
AB  - The management of patients with Hodgkin lymphoma (HL) recurring after stem cell
      transplantation (SCT) and multiply relapsed disease remains challenging. We
      report on 41 such patients who received bendamustine hydrochloride, a
      bifunctional mechlorethamine derivative mechanistically unrelated to traditional
      alkylators, after a median of four prior chemotherapy lines, including SCT in 85%
      of cases. Bendamustine was given at doses of 90-120 mg/m(2) every 21 or 28 d. At
      first assessment (2-4 cycles), the overall response rate (ORR) was 78% with 12
      (29%) complete (CR) and 20 (49%) partial responses (PR). Upon treatment
      prolongation to 6-8 courses, 40% of PRs progressed, yielding a final ORR of 58%
      with 31% of CRs. Eight patients (two CRs, six PRs) were subsequently
      allotransplanted. Median progression-free and overall survival exceeded 11 and 21
      months respectively; complete responders displayed a median disease-free survival
      above 9 months with a relapse rate of only 30%. Outcomes were independent of
      disease chemosensitivity, previous transplant and bendamustine dose-intensity. No
      life-threatening or unexpected adverse events occurred. Within the limits of a
      retrospective analysis and schedule heterogeneity, these results appear very
      encouraging and prompt prospective trials to confirm bendamustine as a valuable
      option in the palliative setting and in cytoreductive strategies before
      allotransplantation.

PMID- 23167438
TI  - Langerhans cell histiocytosis associated with lichen sclerosus of the vulva: case
      report and review of the literature.
AB  - Langerhans cell histiocytosis (LCH) is characterized by a clonal proliferation of
      bone marrow-derived Langerhans cells. While cutaneous involvement is relatively
      common, LCH restricted to the vulvar area is a rare phenomenon and can occur in
      different clinical settings. Occasionally, vulvar LCH heralds subsequent multi
      organ involvement with an aggressive clinical course. Even cases of LCH isolated
      to the vulvar area can present with local recurrences despite excision and
      radiation. We present a case of a 68-year-old female with a 1-month history of
      pruritic lesions on her vulva. Physical examination showed whitish plaques with
      scattered nodular areas on the labia majora. A vulvar biopsy showed a background
      of lichen sclerosus (LS) with foci of oval to polygonal cells with moderately
      abundant eosinophilic cytoplasm and folded nuclei showing frequent nuclear
      grooves. Immunohistochemical staining showed that the cells were positive for
      CD1a and S-100, confirming the diagnosis of LCH. On further workup, there was no
      evidence of disseminated disease involving other organs. While vulvar LCH is
      uncommonly seen, and with only one previous case report in the literature
      associated in the setting of lichen sclerosus, this case illustrates the
      importance of recognizing this condition and ensuring proper clinical follow-up
      to rule out a systemic involvement.

PMID- 23167440
TI  - Gonadotropins Are Related to Lean Mass in Healthy Postmenopausal Women.
AB  - Background. It has been suggested that the changes in hormone levels that occur
      with menopause and aging are related to loss of muscle mass. However, the role of
      gonadotropins in this process is unknown. Objectives. To analyze the relationship
      between follicle-stimulating hormone (FSH) and luteinizing hormone (LH) and lean
      mass in a cohort of healthy women. Methods. This is a cross-sectional study
      including 91 postmenopausal women (48-65 years old). Serum FSH, LH, and estradiol
      (E2) were measured. Lean mass was estimated by bioelectrical impedance analysis
      and expressed as appendicular skeletal muscle mass (AMM) index. Results. AMM
      index was negatively correlated with FSH levels (r = -0.33, p = 0.001) and LH (r
      = -0.293, p = 0.005), while there was no association with E2. When muscle mass
      expressed as AMM index was stratified into tertiles, there were significant
      differences between the lowest and the highest tertile for both FSH (82.4 +/- 30,
      vs. 67.9 +/- 25.8 mIU/mL, p = 0.04) and LH (40.9 +/- 15.2 vs. 36.1 +/- 12.3
      mIU/mL, p = 0.03). In logistic regression analysis adjusted for age and E2
      levels, high concentrations of FSH (OR = 1.03, 95% CI = 1.01-1.05, p = 0.008) and
      LH (OR = 1.06, 95% CI = 1.01-1.1, p = 0.01) were risk factors for having lower
      lean mass expressed as AMM index. Conclusions. Menopausal women with high levels
      of gonadotropins have lower levels of lean mass than those with lower
      gonadotropins levels.

PMID- 23167439
TI  - Proteomic characterization of the Rph15 barley resistance gene-mediated defence
      responses to leaf rust.
AB  - BACKGROUND: Leaf rust, caused by the biotrophic fungal pathogen Puccinia hordei,
      is one of the most important foliar disease of barley (Hordeum vulgare) and
      represents a serious threat in many production regions of the world. The leaf
      rust resistance gene Rph15 is of outstanding interest for resistance breeding
      because it confers resistance to over 350 Puccinia hordei isolates collected from
      around the world. Molecular and biochemical mechanisms responsible for the Rph15
      effectiveness are currently not investigated. The aim of the present work was to
      study the Rph15-based defence responses using a proteomic approach. RESULTS:
      Protein pattern changes in response to the leaf rust pathogen infection were
      investigated in two barley near isogenic lines (NILs), Bowman (leaf rust
      susceptible) and Bowman-Rph15 (leaf rust resistant), differing for the
      introgression of the leaf rust resistance gene Rph15. Two infection time points,
      24 hours and four days post inoculation (dpi), were analysed. No statistically
      significant differences were identified at the early time point, while at 4 dpi
      eighteen protein spots were significantly up or down regulated with a fold-change
      equal or higher than two in response to pathogen infection. Almost all the
      pathogen-responsive proteins were identified in the Bowman-Rph15 resistant NIL.
      Protein spots were characterized by LC-MS/MS analysis and found to be involved in
      photosynthesis and energy metabolism, carbohydrate metabolism, protein
      degradation and defence. Proteomic data were complemented by transcriptional
      analysis of the respective genes. The identified proteins can be related to
      modulation of the photosynthetic apparatus components, re-direction of the
      metabolism to sustain defence responses and deployment of defence proteins.
      CONCLUSIONS: The identification of leaf rust infection-modulated defence
      responses restricted to the resistant NIL support the hypothesis that basal
      defence responses of Bowman, but not the Rph15 resistance gene-based ones, are
      suppressed or delayed by pathogen effectors to levels below the detection power
      of the adopted proteomic approach. Additionally, Rph15-mediated resistance
      processes identified mainly resides on a modulation of primary metabolism,
      affecting photosyntesis and carbohydrate pool.

PMID- 23167441
TI  - Microcirculation inflammation associates with outcome in renal transplant
      patients with de novo donor-specific antibodies.
AB  - In renal transplant patients with de novo donor-specific antibodies (dnDSA) we
      studied the value of microcirculation inflammation (MI; defined by the addition
      of glomerulitis (g) and peritubular capillaritis (ptc) scores) to assess long
      term graft survival in a retrospective cohort study. Out of all transplant
      patients with standard immunological risk (n = 638), 79 (12.4%) developed dnDSA
      and 58/79 (73%) had an indication biopsy at or after dnDSA development. Based on
      the MI score on that indication biopsy patients were categorized, MI0 (n = 26),
      MI1 + 2 (n = 21) and MI >= 3 (n = 11). The MI groups did not differ significantly
      pretransplantation, whereas posttransplantation higher MI scores developed more
      anti-HLA class I + II DSA (p = 0.011), showed more TCMR (p < 0.001) and showed a
      trend to C4d-positive staining (p = 0.059). Four-year graft survival estimates
      from time of indication biopsy were MI0 96.1%, MI1 + 2 76.1% and MI >= 3 17.1%;
      resulting in a 24-fold increased risk of graft failure in the MI >= 3 compared to
      the MI0 group (p = 0.003; 95% CI [3.0-196.0]). When adjusted for C4d, MI >= 3
      still had a 21-fold increased risk of graft failure (p = 0.005; 95% CI [2.5
      180.0]), while C4d positivity on indication biopsy lost significance. In renal
      transplant patients with de novo DSA, microcirculation inflammation, defined by g
      + ptc, associates with graft survival.

PMID- 23167442
TI  - Phasic transition from goal-directed to habitual control over drug-seeking
      produced by conflicting reinforcer expectancy.
AB  - The transition from goal-directed to habitual control over drug-seeking has been
      experimentally demonstrated in animals, but there have been no comparable reports
      in humans. Following a recent animal design, the current study employed an
      outcome-devaluation procedure to test whether goal-directed control over tobacco
      seeking would be abolished by alcohol expectancy. Eighty smokers first learned
      that two responses earned tobacco or chocolate points, respectively, before
      tobacco was devalued by health warnings and smoking satiety. Participants were
      then presented with either a glass of beer/wine or water with instructions that
      this item could be consumed after the task (alternative reward). Then choice
      between the tobacco and chocolate response was measured in extinction to assess
      goal-directed control of tobacco seeking, in a nominal Pavlovian to instrumental
      transfer (PIT) test to assess stimulus control of tobacco seeking, and in a
      reacquisition test to assess the impact of direct feedback from the outcomes. The
      results showed that alcohol expectancy selectively abolished goal-directed
      control of tobacco seeking but not stimulus control or the impact of feedback
      from outcomes. These data suggest that 'endogenous' retrieval of low drug value
      governing goal-directed regulation of drug seeking is disrupted by conflicting
      appraisal of an alternative reinforcer, promoting habitual control, which may
      play a role in relapse.

PMID- 23167444
TI  - Mosquitoes and other aquatic insects in fallow field biotopes and rice paddy
      fields.
AB  - Fallow field biotopes that develop from abandoned rice fields are man-made
      wetlands that provide new habitats for various aquatic animals. Although
      consideration of such biotopes generally focuses on their positive aspects, this
      study evaluated the negative aspects of establishing fallow field biotopes with
      regard to mosquito breeding sites. To determine whether fallow field biotopes
      become breeding habitats for vector mosquitoes, we evaluated mosquito fauna in
      fallow field biotopes and adjacent rice fields. We found larvae of Anopheles
      lesteri, Anopheles sinensis and Culex tritaeniorhynchus (all: Diptera: Culicidae)
      in the biotopes. Although abundances of mosquito larvae in the biotopes and rice
      fields were statistically similar, mosquito abundances in rice fields increased
      dramatically in August when the water level reduced after the rainy season. The
      abundance and variety of the mosquitoes' natural predators were greater in
      biotopes than in rice fields because the former are a permanent and stable
      aquatic environment. A generalized linear mixed model showed a negative effect of
      predator diversity on mosquito larvae abundance in both habitats. Although fallow
      field biotopes become breeding habitats for vector mosquitoes, establishing
      biotopes from fallow fields in order to protect various aquatic animals,
      including mosquito insect predators, may help to control mosquito breeding.

PMID- 23167443
TI  - Oral health and obesity indicators.
AB  - BACKGROUND: In western Sweden, the aim was to study the associations between oral
      health variables and total and central adiposity, respectively, and to
      investigate the influence of socio-economic factors (SES), lifestyle, dental
      anxiety and co-morbidity. METHODS: The subjects constituted a randomised sample
      from the 1992 data collection in the Prospective Population Study of Women in
      Gothenburg, Sweden (n = 999, 38- > =78 yrs). The study comprised a clinical and
      radiographic examination, together with a self-administered questionnaire.
      Obesity was defined as body mass index (BMI) > =30 kg/m(2), waist-hip ratio (WHR)
      > =0.80, and waist circumference >0.88 m. Associations were estimated using
      logistic regression including adjustments for possible confounders. RESULTS: The
      mean BMI value was 25.96 kg/m(2), the mean WHR 0.83, and the mean waist
      circumference 0.83 m. The number of teeth, the number of restored teeth,
      xerostomia, dental visiting habits and self-perceived health were associated with
      both total and central adiposity, independent of age and SES. For instance, there
      were statistically significant associations between a small number of teeth (<20)
      and obesity: BMI (OR 1.95; 95% CI 1.40-2.73), WHR (1.67; 1.28-2.19) and waist
      circumference (1.94; 1.47-2.55), respectively. The number of carious lesions and
      masticatory function showed no associations with obesity. The obesity measure was
      of significance, particularly with regard to behaviour, such as irregular dental
      visits, with a greater risk associated with BMI (1.83; 1.23-2.71) and waist
      circumference (1.96; 1.39-2.75), but not with WHR (1.29; 0.90-1.85). CONCLUSIONS:
      Associations were found between oral health and obesity. The choice of obesity
      measure in oral health studies should be carefully considered.

PMID- 23167445
TI  - Use of heated humidified high-flow nasal cannula oxygen in neonates: a UK wide
      survey.
AB  - AIM: Heated humidified high-flow nasal cannula (HHHFNC) oxygen is a relatively
      new form of respiratory support and is increasing in popularity despite lack of
      supportive evidence and amid safety concerns. We investigated the prevalence of
      its use in tertiary neonatal units in the UK. METHOD: Electronic survey. RESULTS:
      A total of 57 units were contacted and replies received from 44 (77%). HHHFNC was
      used in 34/44 (77%) units. Vapotherm 2000i and Fisher and Paykel RT329 were the
      most popular devices. 39% units used HHHFNC without policies. Most reported use
      in infants of any gestation (24/34, 71%) and weight (26/34, 77%) and for a
      variety of indications including as an alternative to CPAP (26/34, 77%), weaning
      off CPAP (24/34, 71%) and postextubation (18/34, 53%). The flow rates, cannula
      size and mouth position varied widely. The popularity of HHHFNC appeared to be
      its perceived ease of use and improved access to the baby. CONCLUSION: This
      survey demonstrates that HHHFNC is a widely used modality in UK neonatal units.
      Its current use appears to be without clear criteria and mostly based on
      individual preference. In view of doubts about its efficacy and concerns
      regarding safety, this study highlights the urgent need for research to evaluate
      its use in newborns.

PMID- 23167446
TI  - Heat stress activates the Akt/mTOR signalling pathway in rat skeletal muscle.
AB  - AIM: It is well known that various stimuli, such as mechanical stress and
      nutrients, induce muscle hypertrophy thorough the Akt/mTOR signalling pathway,
      which is a key mediator of protein synthesis and hypertrophy in skeletal muscle.
      It was recently reported that heat stress also induces an increase in muscle
      weight and muscle protein content. In addition, heat stress enhances Akt/mTOR
      signalling after one bout of resistance exercise. However, it remains unclear
      whether increased temperature itself stimulates the Akt/mTOR signalling pathway.
      METHODS: Forty-two male Wistar rats (279.5 +/- 1.2 g) were divided into a control
      group (CON) or one of five thermal stress groups at 37, 38, 39, 40 or 41  degrees
      C (n = 7 each group). After overnight fasting, both legs were immersed in
      different temperatures of hot water for 30 min under sodium pentobarbital
      anaesthesia. The soleus and plantaris muscles were immediately removed from both
      legs after the thermal stress. RESULTS: The phosphorylation of mTOR or 4E-BP1 and
      heat shock protein (HSP) expression levels were similar among groups in both the
      soleus and plantaris muscles. However, Akt and p70S6K phosphorylation
      significantly increased at 41  degrees C in the soleus and plantaris muscles.
      Moreover, we observed a temperature-dependent increase in Akt and p70S6K
      phosphorylation in both muscles. CONCLUSION: Our data indicate that the altered
      temperature increased phosphorylation in a temperature-dependent manner in rat
      skeletal muscle and may itself be a key stimulator of Akt/mTOR signalling.

PMID- 23167447
TI  - Physician scarcity in underdeveloped areas of Turkey: what do new graduate
      physicians think?
AB  - INTRODUCTION: A sufficient and balanced distribution of physicians plays a key
      role in access to high quality healthcare services. However, this issue presents
      serious problems globally. Turkey is currently experiencing physician shortages,
      with insufficient numbers of physicians in its rural and underdeveloped areas.
      The objectives of this study were to identify the views of new graduate
      physicians, prior to employment, on working in underdeveloped areas, in order to
      discover factors impacting their desire to work in these areas, and to show the
      actual geographic distribution of physicians in Turkey. This provides the basis
      for discussing future policies. METHODS: This study was conducted in Turkey from
      September to November 2009. All physicians (N=4753) who graduated in 2009 were
      included in the study via online questionnaires. The response rate was 78%.
      Variables potentially related to physicians' decisions to work in underdeveloped
      areas were analyzed using the chi(2) test. To discover the imbalance in
      geographic distribution of physicians, data collected by the Turkish Ministry of
      Health (MoH) were re-analyzed. Physician density was calculated for the six zones
      determined by the MoH according to socioeconomic development. RESULTS: Of the
      physicians who participated, 52.5% were male and 13.5% expressed a desire to work
      in underdeveloped areas. Male physicians were more likely to work in
      underdeveloped areas (17.5% and 9.1%, respectively; p<0.05). There was a
      significant relationship between desire to work in underdeveloped areas, regions
      of longest stay and birthplace (p<0.05). Physicians who had lived for a
      significant period in areas with a high number of underdeveloped cities
      (Southeastern and Eastern Turkey) and those who were born in underdeveloped
      cities were more likely to wish to work in these areas. The most influential
      factor for working in these areas was higher salaries. CONCLUSIONS: Physicians
      who have particular socioeconomic backgrounds such as rural origin and lower
      background-family income are more likely to have be motivated to work in
      underdeveloped areas. They are also more likely to accept work in these areas if
      financial and non-financial opportunities are provided. The findings of this
      study provide guidance for those revising health workforce policies.

PMID- 23167449
TI  - Controls on the redox potential of rainwater.
AB  - Hydrogen peroxide acting as a reductant affects the redox potential of rainwater
      collected at the Bermuda Atlantic Time Series Station, the South Island of New
      Zealand, the contiguous USA, and the primary study site in Wilmington, NC.
      Analytical measurements of both halves of redox couples for dissolved iron,
      mercury, and the nitrate-nitrite-ammonium system can predict the rainwater redox
      potential measured directly by a platinum electrode. Measurements of these redox
      couples along with the pH in rain yields pe- between 8 and 11; the half reaction
      for hydrogen peroxide acting as a reductant using typical rainwater conditions of
      15 MUM H2O2 at pH 4.7 gives pe- = 9.12, where pe- = negative log of the activity
      of hydrated electrons. Of the six rainwater redox systems investigated, only
      manganese speciation appeared to be controlled by molecular oxygen (pe- = 15.90).
      Copper redox speciation was consistent with superoxide acting as a reductant (pe-
      = 2.7). The concentration of H2O2 in precipitation has more than doubled over the
      preceding decade due to a decrease in SO2 emissions, which suggests the redox
      chemistry of rainwater is dynamic and changing, potentially altering the
      speciation of many organic compounds and trace metals in atmospheric waters.

PMID- 23167448
TI  - Cortisol levels are influenced by sedation in the acute phase after subarachnoid
      haemorrhage.
AB  - BACKGROUND: Subarachnoid haemorrhage (SAH) is a life-threatening condition that
      may be aggravated by acute pituitary damage and cortisol insufficiency. Robust
      diagnostic criteria for critical illness-related corticosteroid insufficiency
      (CIRCI) are lacking. The aim of this study was to assess the frequency of CIRCI
      in the acute phase (0-240 h) after SAH and to evaluate associations between
      cortisol levels and clinical parameters (sedation, circulatory failure, gender,
      age, severity of disease, treatment). CIRCI was defined as a single morning serum
      cortisol (mSC) < 200 nmol/L. The lower limit for calculated free cortisol (cFC)
      was set at < 22 nmol/L, and for saliva cortisol at < 7.7 nmol/L. METHODS: Fifty
      patients were included. Serum/saliva cortisol and corticosteroid-binding globulin
      were obtained every second morning. A logistic regression model was used for
      multivariate analysis comparing cortisol levels with clinical parameters.
      RESULTS: Of the patients, 21/50 (42%) had an mSC < 200 nmol/L and 30/50 (60%) had
      a cFC < 22 nmol/L. In patients with continuous intravenous sedation, the odds
      ratio for a mSC to be < 200 nmol/L was 18 times higher (95% confidence interval
      4.2-85.0, P < 0.001), and the odds ratio for a cFC to be < 22 nmol/L was 2.4
      times higher (95% confidence interval 1.2-4.7, P < 0.05) compared with patients
      with no continuous intravenous sedation. CONCLUSIONS: Continuous intravenous
      sedation was significantly associated with cortisol values under defined limits
      (mSC < 200, cFC < 22 nmol/L). The possibility that sedating drugs per se may
      influence cortisol levels should be taken into consideration before CIRCI is
      diagnosed.

PMID- 23167450
TI  - Limb preferences in non-human vertebrates.
AB  - There is considerable debate about whether population-level asymmetries in limb
      preferences are uniquely human or are a common feature among vertebrates. In the
      present article the results of studies investigating limb preferences in all non
      extinct vertebrate orders are systematically analysed by employing cladographic
      comparisons. These studies analysed 119 different species, with 61 (51.26%)
      showing evidence for population-level asymmetries, 20 (16.81%) showing evidence
      for individual-level asymmetries and 38 (31.93%) showing no evidence for
      asymmetry. The cladographic comparison revealed that research in several key taxa
      in particular (e.g., Chondrichtyes, Crocodylia, Atlantogenata and Palaeognathae)
      would have important implications for our understanding of the evolution of
      vertebrate limb preferences. Furthermore, the findings of the present study
      support the position that population-level asymmetries in limb preferences as
      such represent a common vertebrate feature. Looking into the details, however,
      some important differences from human handedness become visible: Non-human limb
      preferences typically show a less-skewed lateralisation pattern and there are
      larger numbers of individuals without a preference in most species compared to
      humans. Moreover, limb preferences in non-human animals are often less task
      invariant than human handedness and are more frequently modulated by external
      factors and individual characteristics. 

PMID- 23167452
TI  - Modulation of potential respiratory pathogens by pH1N1 viral infection.
AB  - While much effort has been made to characterize influenza A pdm09 virus (pH1N1),
      the flu that was responsible for the fourth influenza pandemic, there is a lack
      of study on the composition of bacteria that lead to secondary infection. In this
      study, we recruited pneumonia patients with and without pH1N1 infection and
      characterized their oropharyngeal microbiota by the unbiased high-throughput
      sequencing method. While there were no significant differences in common
      bacterial pneumonia-causative agents (Acinetobacter and Streptococcus species),
      previously unreported Pseudomonas species equipped with chemotaxis and flagellar
      assembly genes significantly increased (>20-fold) in the pH1N1-infected group.
      Bacillus and Ralstonia species that also increased significantly (5-10-fold) were
      also found to possess similar signaling and motility genes. In contrast, no such
      genes were found in oral commensal Prevotella, Veillonella and Neisseria species,
      which decreased significantly, or in either Acinetobacter or 10 out of 21
      Streptococcus species, including Streptococcus pneumoniae. Our results support
      the notion that pH1N1 infection provides a niche for previously unnoticed
      potential respiratory pathogens that were able to access the lower respiratory
      tract with weakened immunity. 

PMID- 23167453
TI  - Sorrow, coping and resiliency: parents of children with cerebral palsy share
      their experiences.
AB  - PURPOSE: To explore the grieving, coping and resiliency experiences of parents of
      children with cerebral palsy (CP) and to investigate the suitability of chronic
      sorrow theory as a framework to understand those experiences. METHODS: This study
      combined focus groups with a web-based cross-sectional survey to explore chronic
      sorrow in parents of children with CP. Eight parents of children with CP
      participated in focus groups. The discussion was transcribed verbatim and
      thematic analysis was performed. A further 94 parents participated in the web
      based survey study in which they completed the Adapted Burke Questionnaire on
      chronic sorrow. A content analysis of responses was used to confirm the primary
      qualitative analysis. RESULTS: The reports of parents in the focus group were
      consistent with chronic sorrow theory, as were the responses of parents to the
      web-based survey. Some parents found the diagnosis itself a distressing time
      whereas others found it a relief. Parents reported that times of medical and
      allied health intervention were particularly challenging. CONCLUSION: Chronic
      sorry theory is a useful way of understanding the experiences of parents of
      children with CP. It is recommended that health practitioners are mindful that,
      even years after diagnosis, parents of children with CP may experience
      intensified chronic sorrow symptoms following a triggering event and that this is
      normal.

PMID- 23167454
TI  - Effect of remote picolinyl and picoloyl substituents on the stereoselectivity of
      chemical glycosylation.
AB  - O-picolinyl and O-picoloyl groups at remote positions (C-3, C-4, and C-6) can
      mediate glycosylation reactions by providing high or even complete facial
      selectivity for the attack of the glycosyl acceptor. The set of data presented
      herein offers a strong evidence of the intermolecular H-bond tethering between
      the glycosyl donor and glycosyl acceptor counterparts while providing a practical
      new methodology for the synthesis of either 1,2-cis or 1,2-trans linkages.
      Challenging glycosidic linkages including alpha-gluco, beta-manno, and beta
      rhamno have seen obtained with high or complete stereocontrol.

PMID- 23167455
TI  - Does ozone-water complex produce additional OH radicals in the atmosphere?
AB  - Ozone-water complex has been thought to play a role in producing atmospheric OH
      radicals through its photolysis. Here, we re-examined the absorption cross
      section of the ozone-water complex with a new method to tell whether the above
      speculation is valid. With argon solvation and photoionization by tunable vacuum
      ultraviolet light, we were able to selectively probe the ozone-water 1:1 complex.
      The measured cross-section of the complex is only similar to the sum of the cross
      sections of ozone and water monomers at 157.6, 248.4, and 308.4 nm. In addition,
      we did not observe any absorption of the complex at 351.8 nm. The results
      indicate that the OH production through the photolysis of the ozone-water complex
      is much slower than previously thought.

PMID- 23167451
TI  - Physical activity in obesity and metabolic syndrome.
AB  - Biological aging is typically associated with a progressive increase in body fat
      mass and a loss of lean body mass. Owing to the metabolic consequences of reduced
      muscle mass, it is understood that normal aging and/or decreased physical
      activity may lead to a higher prevalence of metabolic disorders. Lifestyle
      modification, specifically changes in diet, physical activity, and exercise, is
      considered the cornerstone of obesity management. However, for most overweight
      people it is difficult to lose weight permanently through diet or exercise. Thus,
      prevention of weight gain is thought to be more effective than weight loss in
      reducing obesity rates. A key question is whether physical activity can extenuate
      age-related weight gain and promote metabolic health in adults. Current
      guidelines suggest that adults should accumulate about 60 minutes of moderate
      intensity physical activity daily to prevent unhealthy weight gain. Because
      evidence suggests that resistance training may promote a negative energy balance
      and may change body fat distribution, it is possible that an increase in muscle
      mass after resistance training may be a key mediator leading to better metabolic
      control.

PMID- 23167456
TI  - Pectin-cellulose interactions in the Arabidopsis primary cell wall from two
      dimensional magic-angle-spinning solid-state nuclear magnetic resonance.
AB  - The primary cell wall of higher plants consists of a mixture of polysaccharides
      whose spatial proximities and interactions with each other are not well
      understood. We recently obtained the first two-dimensional (2D) and three
      dimensional high-resolution magic-angle-spinning (13)C solid-state nuclear
      magnetic resonance spectra of the uniformly (13)C-labeled primary cell wall of
      Arabidopsis thaliana, which allowed us to assign the majority of (13)C resonances
      of the three major classes of polysaccharides: cellulose, hemicellulose, and
      pectins. In this work, we measured the intensity buildup of (13)C-(13)C cross
      peaks in a series of 2D (13)C correlation spectra to obtain semiquantitative
      information about the spatial proximities between different polysaccharides.
      Comparison of 2D spectra measured at different spin diffusion mixing times
      identified intermolecular pectin-cellulose cross-peaks as well as interior
      cellulose-surface cellulose cross-peaks. The intensity buildup time constants are
      only modestly longer for cellulose-pectin cross-peaks than for interior cellulose
      surface cellulose cross-peaks, indicating that pectins come into direct contact
      with the cellulose microfibrils. Approximately 25-50% of the cellulose chains
      exhibit close contact with pectins. The (13)C magnetization of the wall
      polysaccharides is not fully equilibrated by 1.5 s, indicating that pectins and
      cellulose are not homogeneously mixed on the molecular level. We also assigned
      the (13)C signals of cell wall proteins, identifying common residues such as Pro,
      Hyp, Tyr, and Ala. The chemical shifts indicate significant coil and sheet
      conformations in these structural proteins. Interestingly, few cross- peaks were
      observed between the proteins and the polysaccharides. Taken together, these data
      indicate that the three major types of polysaccharides in the primary wall of
      Arabidopsis form a single cohesive network, while structural proteins form a
      relatively separate domain.

PMID- 23167457
TI  - Renal transplantation in systemic amyloidosis-importance of amyloid fibril type
      and precursor protein abundance.
AB  - Renal transplantation remains contentious in patients with systemic amyloidosis
      due to the risk of graft loss from recurrent amyloid and progressive disease.
      Outcomes were sought among all patients attending the UK National Amyloidosis
      Centre who received a renal transplant (RTx) between January 1978 and May 2011. A
      total of 111 RTx were performed in 104 patients. Eighty-nine percent of patients
      with end-stage renal disease (ESRD) due to hereditary lysozyme and apolipoprotein
      A-I amyloidosis received a RTx. Outcomes following RTx were generally excellent
      in these diseases, reflecting their slow natural history; median graft survival
      was 13.1 years. Only 20% of patients with ESRD due to AA, AL and fibrinogen
      amyloidosis received a RTx. Median graft survival was 10.3, 5.8 and 7.3 years in
      these diseases respectively, and outcomes were influenced by fibril precursor
      protein supply. Patient survival in AL amyloidosis was 8.9 years among those who
      had achieved at least a partial clonal response compared to 5.2 years among those
      who had no response (p = 0.02). Post-RTx chemotherapy was administered
      successfully to four AL patients. RTx outcome is influenced by amyloid type.
      Suppression of the fibril precursor protein is desirable in the amyloidoses that
      have a rapid natural history.

PMID- 23167458
TI  - Phagocytic blasts in B-lineage acute lymphoblastic leukaemia.

PMID- 23167459
TI  - Comparison of left atrial mechanical function in nondipper versus dipper
      hypertensive patients: a speckle tracking study.
AB  - AIM: Nondippers are known to carry a high risk of cardiovascular morbidity and
      mortality. The aim of this study was to investigate the effects of dipper and
      nondipper status of hypertension on longitudinal systolic and diastolic functions
      of left atrial (LA) myocardial tissue by means of two-dimensional speckle
      tracking echocardiography in treated hypertensive patients. METHODS: A total of
      78 outpatients treated with antihypertensive drugs for at least 1 year were
      included in the study. The patients were classified as nondippers if their
      daytime ambulatory systolic and diastolic blood pressure did not decrease by at
      least 10% during the night. Global longitudinal LA strain/strain rate data were
      obtained by two-dimensional speckle imaging with automated software and compared
      between the groups. RESULTS: LA volume index, left ventricular (LV) wall
      thickness and mass index as well as filling pressure (E/E') were significantly
      higher in nondippers (all P < 0.001), whereas systolic tissue velocity (S') was
      significantly lower in nondippers. They also had decreased values of mean peak LA
      strain (dippers = 27.6 +/- 5.5% vs. nondippers = 21.5 +/- 4.5%, P < 0.001),
      strain rate during reservoir (dippers = 1.27 +/- 0.4/sec vs. nondippers = 0.98 +/
      0.3/sec, P = 0.001), and conduit period (dippers = 1.41 +/- 0.4/sec vs.
      nondippers = 1.06 +/- 0.3/sec, P < 0.001). Moreover, we found that LA mechanical
      dysfunction was closely associated with LV mass, filling pressure, and regional
      LV contractility. CONCLUSION: Nondipping in treated hypertensive patients was
      associated with an adverse cardiac remodeling and impaired LA mechanical
      function. Further studies are warranted to demonstrate the long-term prognostic
      significance of these findings.

PMID- 23167461
TI  - Effect of Testosterone on Inflammatory Markers in the Development of Early
      Atherogenesis in the Testicular-Feminized Mouse Model.
AB  - Background. Low levels of serum testosterone in men are associated with
      cardiovascular disease. Clinical studies show that testosterone replacement
      therapy (TRT) can improve symptoms of cardiovascular disease and reduce the
      inflammatory burden evident in atherosclerosis. Aim. We used an in vivo animal
      model to determine whether testosterone influences mediators of vascular
      inflammation as part of its beneficial effects on atherogenesis. Methods.
      Testicular-feminized (Tfm) mice, which express low endogenous testosterone and a
      non-functional androgen receptor (AR), were used to assess the effect of androgen
      status on atheroma formation, serum lipids, and inflammatory mediators. Tfm mice
      were fed a high-cholesterol diet, received saline or physiological (TRT), and
      were compared to saline-treated XY littermates. Results. A total of 28 weeks of
      high-cholesterol diet caused fatty streak formation in the aortic root of XY
      littermates and Tfm mice, an effect significantly amplified in Tfm mice. Tfm mice
      on normal diet showed elevated serum tumor necrosis factor-alpha (TFN-alpha) and
      interleukin-6 compared to XY littermates. High-cholesterol diet induced increased
      monocyte chemoattractant protein-1 (MCP-1) in Tfm mice, and TFN-alpha and MCP-1
      in XY littermates. TRT reduced fatty streak formation and serum interleukin-6 in
      Tfm mice but had no significant effects on lipid profiles. Monocyte/macrophage
      staining indicated local inflammation in aortic root fatty streak areas of all
      mice, with TRT reducing local inflammation through plaque reduction in Tfm mice.
      Fractalkine (CX(3)CL1) and its receptor (CX(3)CR1) were present in fatty streaks
      of all mice fed a high-cholesterol diet, independent of androgen status.
      Conclusion. These results are consistent with AR-dependent and AR-independent
      anti-inflammatory actions of testosterone in atheroprotection, although the local
      anti-inflammatory mechanisms via which testosterone acts remain unknown.

PMID- 23167460
TI  - Tumor response evaluation criteria for HCC (hepatocellular carcinoma) treated
      using TACE (transcatheter arterial chemoembolization): RECIST (response
      evaluation criteria in solid tumors) version 1.1 and mRECIST (modified RECIST):
      JIVROSG-0602.
AB  - BACKGROUND: Two standard sets of criteria are used to evaluate the tumor response
      of hepatocellular carcinoma (HCC): RECIST (Response Evaluation Criteria in Solid
      Tumors) and modified RECIST (mRECIST). The purpose was to compare two tumor
      response evaluation criteria, RECIST version 1.1 and mRECIST, for HCC treated
      using transcatheter arterial chemoembolization (TACE). METHODS: The radiological
      findings of patients who underwent TACE for HCCs in a multicenter clinical trial
      were examined. Sixty-five lesions in 21 patients treated with TACE without mixing
      iodized-oil were evaluated. The tumor size was evaluated by measuring the entire
      lesion, including the necrotic part, using RECIST version 1.1, whereas only the
      contrast-enhanced part observed during the arterial phase was measured using
      mRECIST. Five radiologists independently measured each lesion twice. To evaluate
      the inter-criteria reproducibility, the complete response (CR) rate, the response
      rate, the kappa statistics, and the proportion of agreement (PA) for response
      categories were calculated. The same analyses were conducted for inter- and intra
      observer reproducibility. RESULTS: In the inter-criteria reproducibility study,
      the CR rate and the response rate obtained using mRECIST (56.9% and 79.7%) were
      higher than those obtained using RECIST version 1.1 (9.2% and 43.1%). In the
      inter- and intra-observer reproducibility study, mRECIST exhibited an 'almost
      perfect agreement', while RECIST version 1.1 exhibited a 'substantial agreement'.
      CONCLUSIONS: Considerable differences in the CR rate and the response rate were
      observed. From the viewpoint of the high inter- and intra-observer
      reproducibility, mRECIST may be more suitable for tumor response criteria in
      clinical trials of TACE for HCC.

PMID- 23167462
TI  - Vascular plant one-zinc-finger protein 1/2 transcription factors regulate abiotic
      and biotic stress responses in Arabidopsis.
AB  - Plants adapt to abiotic and biotic stresses by activating abscisic acid-mediated
      (ABA) abiotic stress-responsive and salicylic acid-(SA) or jasmonic acid-mediated
      (JA) biotic stress-responsive pathways, respectively. Although the abiotic stress
      responsive pathway interacts antagonistically with the biotic stress-responsive
      pathways, the mechanisms that regulate these pathways remain largely unknown. In
      this study, we provide insight into the function of vascular plant one-zinc
      finger proteins (VOZs) that modulate various stress responses in Arabidopsis. The
      expression of many stress-responsive genes was changed in the voz1voz2 double
      mutant under normal growth conditions. Consistent with altered stress-responsive
      gene expression, freezing- and drought-stress tolerances were increased in the
      voz1voz2 double mutant. In contrast, resistance to a fungal pathogen,
      Colletotrichum higginsianum, and to a bacterial pathogen, Pseudomonas syringae,
      was severely impaired. Thus, impairing VOZ function simultaneously conferred
      increased abiotic tolerance and biotic stress susceptibility. In a chilling
      stress condition, both the VOZ1 and VOZ2 mRNA expression levels and the VOZ2
      protein level gradually decreased. VOZ2 degradation during cold exposure was
      completely inhibited by the addition of the 26S proteasome inhibitor, MG132, a
      finding that suggested that VOZ2 degradation is dependent on the ubiquitin/26S
      proteasome system. In voz1voz2, ABA-inducible transcription factor CBF4
      expression was enhanced significantly even under normal growth conditions,
      despite an unchanged endogenous ABA content. A finding that suggested that VOZs
      negatively affect CBF4 expression in an ABA-independent manner. These results
      suggest that VOZs function as both negative and positive regulators of the
      abiotic and biotic stress-responsive pathways, and control Arabidopsis adaptation
      to various stress conditions.

PMID- 23167464
TI  - Cellular turnover in epithelial rests of Malassez in the periodontal ligament of
      the mouse molar.
AB  - Fragments of Hertwig's epithelial root sheath persist in the periodontal ligament
      (PDL) in small clusters known as epithelial rests of Malassez (ERM). It is
      generally agreed that ERM are maintained as a quiescent and exclusively dental
      epithelial cluster in PDL. However, we speculate that homeostasis and cellular
      turnover underlies cluster maintenance. We also hypothesize that the fate of ERM
      clusters - diminishing or remaining - might be regulated via the presence or
      absence of epithelial stem cells therein. Histological analysis of aging mouse
      molar PDL showed that ERM clusters gradually increase in size with increasing
      age. Immunocytochemistry and cell culture revealed that ERM clusters contained
      Ki67-positive cells and were able to expand when brought in culture. The TdT
      mediated biotin-dUTP nick-end labeling (TUNEL) procedure also detected signs of
      apoptosis. Finally, we identified putative epithelial stem cells in the clusters
      by 5-bromo-2'-deoxyuridine (BrdU) pulse-chase experiments and
      immunohistochemistry, using the stem-cell marker leucine-rich repeat-containing G
      protein-coupled receptor 5 (Lgr5). The results suggest that ERM clusters are
      maintained in the PDL, via cellular turnover, throughout life.

PMID- 23167463
TI  - Epithelial-mesenchymal interactions induce enamel matrix proteins and proteases
      in the epithelial cells of the rests of Malassez in vitro.
AB  - Epithelial-mesenchymal interactions influence morphogenesis and cell
      differentiation in periodontal tissue regeneration. The current study examined
      the expression of amelogenin, ameloblastin, matrix metallopeptidase-20 (MMP-20),
      and kallikrein-4 (KLK-4) and their effects on the interactions between the
      epithelial cells of Malassez and periodontal ligament fibroblasts. Explants of
      human periodontal ligament tissues produced outgrowths containing both the
      epithelial cells of Malassez and periodontal ligament fibroblasts after
      incubation in a modified serum-free medium. Both the epithelial cells and
      fibroblasts were co-cultured in the same dish. The distribution and expression of
      all four factors were evaluated using immunohistochemistry, in-situ hybridization
      and RT-PCR analysis. The epithelial cells of Malassez were cultured separately
      and were used as the control. Immunohistochemical analysis revealed weak
      expression of amelogenin, ameloblastin, MMP-20 and KLK-4 in epithelial cells of
      Malassez co-cultured with periodontal ligament fibroblasts. in-situ hybridization
      and RT-PCR confirmed significant mRNA expression of these factors in co-cultured
      cells compared with control cells. MMP20 mRNA was not expressed in control cells.
      These results suggest that the epithelial-mesenchymal interactions promote
      differentiation of human epithelial cells of Malassez and that the induction of
      enamel matrix proteases facilitates the degradation of enamel matrix proteins.

PMID- 23167465
TI  - Localization of c-MYB in differentiated cells during postnatal molar and alveolar
      bone development.
AB  - The MYB family of transcription activators has been associated with a high
      proliferation rate and an undifferentiated state of cells in a number of tissues.
      Recently emerging data suggest that these molecules may also play a role in
      differentiation. In this study, the pattern of expression of c-MYB was followed
      during postnatal stages of mouse molar odontogenesis using immunohistochemistry
      on serial sections. Along with an abundance of the c-MYB protein in proliferating
      zones, we confirmed the presence of this protein in differentiated ameloblasts,
      odontoblasts, and osteoblasts. In addition, c-MYB was also found in cementoblasts
      and alveolar fibroblasts. These findings suggest integration of c-MYB into
      regulatory networks during hard-tissue differentiation and mineralization.

PMID- 23167466
TI  - Synaptic vesicle protein 2b is expressed temporospatially in (pre)odontoblasts in
      developing molars.
AB  - The formation of dentin and enamel is initiated by the differentiation of
      odontogenic precursor cells into odontoblasts and ameloblasts, respectively. This
      study was performed to identify new molecules involved in the differentiation of
      odontogenic cells. The genes expressed differentially between the root stage
      (after the differentiation of odontogenic cells and dental hard-tissue formation)
      and the cap stage (before the differentiation of odontogenic cells and dental
      hard-tissue formation) were searched using differential display PCR. For the
      first time, synaptic vesicle protein (SV) 2b, an important transmembrane
      transporter of Ca(2+) -stimulated vesicle exocytosis, was identified as a
      differentially expressed molecule. Real-time PCR and western blotting revealed an
      increase in the transcriptional and translational levels of SV2b during or after
      the differentiation of odontogenic cells. Immunofluorescence revealed this
      molecule to be localized in not only fully differentiated odontoblasts but also
      in pre-odontoblasts before dentin matrix secretion. The expression pattern of the
      SV2a isoform was similar to that of the SV2b isoform, whereas the SV2c isoform
      showed a contrasting pattern of expression. After treatment with alendronate, an
      inhibitor of protein isoprenylation for the transport of secretory vesicles, the
      expression of SV2a and SV2b decreased, whereas that of SV2c increased. These
      results suggest that the SV2 isoforms are functional molecules of
      (pre)odontoblasts which may be involved in vesicle transport.

PMID- 23167467
TI  - Enamel matrix derivative induces production of vascular endothelial cell growth
      factor in human gingival fibroblasts.
AB  - Enamel matrix derivative (EMD) may enhance periodontal wound healing by inducing
      angiogenesis. We sought to investigate the effect and the mechanism of action of
      EMD on vascular endothelial growth factor (VEGF) production by human gingival
      fibroblasts. Cells were stimulated with EMD, transforming growth factor-beta1
      (TGF-beta1), or fibroblast growth factor 2 (FGF-2), with or without antibodies to
      TGF-beta1 or FGF-2. The levels of VEGF in the culture media were measured using
      an ELISA. We examined the effects of SB203580 [a p38 mitogen-activated protein
      kinase (MAPK) inhibitor], U0126 [an extracellular signal-regulated kinase (ERK)
      inhibitor], SP600125 [a c-Jun N-terminal kinase (JNK) inhibitor], and LY294002 [a
      phosphatidylinositol 3-kinase (PI3K)/Akt inhibitor] on EMD-induced VEGF
      production. Enamel matrix derivative stimulated the production of VEGF in a dose-
      and time-dependent manner. Treatment of human gingival fibroblasts with
      antibodies to TGF-beta1 or FGF-2 significantly decreased EMD-induced VEGF
      production, whereas the addition of exogenous TGF-beta1 and FGF-2 stimulated VEGF
      production. Enamel matrix derivative-induced VEGF production was significantly
      attenuated by SB203580, U0126, and LY294002. Our results suggest that EMD
      stimulates VEGF production partially via TGF-beta1 and FGF-2 in human gingival
      fibroblasts and that EMD-induced VEGF production is regulated by ERK, p38 MAPK,
      and PI3K/Akt pathways. Enamel matrix derivative-induced production of VEGF by
      human gingival fibroblasts may be involved in the enhancement of periodontal
      wound healing by inducing angiogenesis.

PMID- 23167468
TI  - Impact of response shift on the assessment of treatment effects using the Oral
      Health Impact Profile.
AB  - The assessment of changes in oral health-related quality of life (OHRQoL) is
      challenging because individuals' concepts and internal standards of OHRQoL may
      change over time. The aim of this study was to detect response shifts in OHRQoL
      assessments made using the Oral Health Impact Profile (OHIP). Oral health-related
      quality of life was assessed in a consecutive sample of 126 patients seeking
      prosthodontic care. Patients were asked to rate their OHRQoL before treatment
      started and 1 month after treatment was finished, using the German 49-item
      version of the OHIP. When rating their OHRQoL after treatment, patients were also
      asked to rate their pre-treatment OHRQoL without having access to their baseline
      data. The response shift was calculated as the difference in OHIP summary scores
      between the initial assessment and the retrospective baseline assessment. The
      OHIP mean scores decreased from 31.8 at the initial baseline assessment to 24.4
      after treatment. The retrospective baseline assessment resulted in an OHIP mean
      score of 38.1, corresponding to a response shift of 6.3 OHIP points. The effect
      size (Cohen's d = 0.21) of the response shift was considered small. The response
      shift phenomenon and its magnitude have important implications for dental
      practice, where patients and dentists often assess perceived treatment effects
      retrospectively.

PMID- 23167469
TI  - Effects of delayed-onset muscle soreness on masticatory function.
AB  - The aim was to clarify the effects of experimentally provoked delayed-onset
      muscle soreness (DOMS) in the jaw-closing muscles on subjective and objective
      measures of masticatory function. Twenty-one dentate female subjects, without
      pain-related signs and symptoms of temporomandibular disorders, participated.
      Delayed-onset muscle soreness was provoked with eccentric and concentric
      contractions of the jaw-closing muscles using a custom-made apparatus. At
      baseline, and 24 h and 1 wk after the exercises, data were gathered on the
      subjective measures of muscle fatigue, muscle pain, and masticatory chewing
      ability using visual analogue scale (VAS) scores, on the maximum voluntary bite
      force (MVBF), and on the food Mixing Ability Index (MAI). After 24 h, muscle
      fatigue and muscle pain had increased and the MAI had decreased. All had returned
      to baseline levels after 1 wk. There were no significant changes found in the
      chewing ability VAS scores and in the MVBF over time. After correction for its
      baseline value, the MAI after 24 h was found to be significantly related to the
      muscle pain after 24 h. In conclusion, DOMS in the jaw-closing muscles can cause
      a decrease in the objectively scored chewing ability, while the subjectively
      scored chewing ability remained the same.

PMID- 23167470
TI  - Risk indicators for dental erosive wear among 18-yr-old subjects in Oslo, Norway.
AB  - The aim was to investigate risk indicators associated with dental erosive wear
      among 18-yr-old subjects in Oslo, Norway. Of 3,206 adolescents invited to
      participate in a screening examination for erosive wear, 1,456 were examined
      (giving a response rate of 45%). As part of the examination all participants
      completed a self-administered questionnaire. Associations between the presence of
      erosive lesions and the possible risk indicators were assessed by logistic
      regression analyses, taking into account the hierarchical relationships between
      the independent variables. Of all 18-yr-old subjects examined, 38% had at least
      one tooth with erosive lesions. Multivariate analyses showed significant
      associations between the presence of erosive wear and being male, brushing teeth
      once per day or less, episodes of vomiting, daily/weekly episodes of gastro
      oesophageal reflux, consumption of fruit juice and sugary soft drinks several
      times per day, as well as consumption of sugary soft drinks daily to once per
      week. In conclusion, in addition to gender, dietary habits such as frequent
      consumption of fruit juice and sugary soft drinks, and the occurrence of reflux
      and vomiting, appear to be risk indicators for erosive wear. When counselling
      adolescents at risk, the gender-specific risk indicators should be taken into
      account.

PMID- 23167471
TI  - Longevity of posterior dental restorations and reasons for failure.
AB  - Tooth-coloured restorative materials are being used increasingly more often in
      Class II preparations in permanent teeth. Using a practice-based study design, we
      aimed to assess the survival time of Class II restorations and to identify
      factors relevant to their longevity. Class II restorations (n = 4,030),
      consisting of resin composites (81.5%), compomers (12.7%), amalgams (4.6%), and
      glass-ionomer cement restorations (1.2%), were placed in 1,873 patients with a
      median age of 15 yr. In total, 92.7% of restorations were placed due to primary
      caries and 5.8% were replacements. After an average follow-up period of 4.6 yr,
      61.6% of the restorations were successful, 11.2% had failed, and 27.2% were not
      available for evaluation (owing to patient drop-out). The mean annual failure
      rate was 2.9% for resin-composite restorations and 1.6% for amalgams. For resin
      composite restorations, secondary caries was the most common reason for
      replacement (73.9%), followed by loss (8.0%), fracture (5.3%), and marginal
      defects (2.4%). Multilevel Cox-regression analyses identified young age of the
      patient, high previous caries experience, deep cavities, and saucer-shaped
      preparation technique as predisposing to shorter longevity of resin-composite
      restorations. One brand of resin composite had a shorter survival time than the
      others.

PMID- 23167472
TI  - Dental age in patients with neurofibromatosis 1.
AB  - Neurofibromatosis type 1 (NF1) is a common, hereditary, neurocutaneous skeletal
      condition with a variety of osseous manifestations. Although NF1 also affects
      craniofacial structures, the literature has only limited information related to
      the effect of NF1 on dental development. In this study the dental age of 34
      Finnish NF1 patients, 8-17 yr of age, was estimated using the Demirjian &
      Goldstein method. The dental age of children with NF1 was similar to that of a
      Finnish control population. The findings suggest that NF1 does not affect the
      timing of tooth development.

PMID- 23167473
TI  - Further evidence of association of the ABCA4 gene with cleft lip/palate.
AB  - Non-syndromic cleft lip with or without cleft palate (CL/P) is a common birth
      defect with a complex etiology. Numerous genes and environmental factors, and
      their interactions, are thought to play a role in the susceptibility to CL/P. A
      recent genome-wide association study with several populations revealed markers
      in/near transcription factor vmaf musculoaponeurtoic fibrosarcoma oncogene
      homolog B (MAFB) and ATP-binding cassette sub-family A member 4 (ABCA4) genes as
      new susceptibility loci for CL/P. We hypothesized that these genes could also
      contribute to CL/P in a Brazilian population, and hence we evaluated if the
      associated single-nucleotide polymorphisms (SNPs) in MAFB (rs13041247 and
      rs11696257) and ABCA4 (rs560426 and rs481931) were associated with CL/P in our
      case-control data set. We genotyped 812 Caucasian individuals (400 cases and 412
      controls) from Brazil. Allele frequencies were compared for cases and controls as
      well as for cleft subgroups and controls. ABCA4 rs540426 showed strong
      associations with CL/P, unilateral and right CL/P, and bilateral CL/P, whereas
      the SNP rs481931 showed borderline associations with CL/P and bilateral CL/P . No
      association was found for MAFB. Our results support a potential role for ABCA4 in
      the etiology of CL/P in individuals from Brazil.

PMID- 23167474
TI  - Effect of hydroxyapatite film formed by powder jet deposition on dentin
      permeability.
AB  - A powder jet deposition (PJD) process can be used to create a thick
      hydroxyapatite (HA) film on the surface of a human tooth. This study aimed to
      investigate in vitro the ability of an HA film, applied using PJD, to diminish
      dentin permeability. Discs of human coronal dentin were cut perpendicular to the
      tooth axis and the smear layer was removed by EDTA treatment. The HA film was
      created by accelerating HA particles, calcinated at 1200 degrees C, onto the
      dentin discs at room temperature and atmospheric pressure. The surfaces and cross
      sections of the HA PJD-treated samples were observed using scanning electron
      microscopy. Their permeability was indirectly recorded with a split-chamber
      device utilizing a chemiluminescence technique. MS-coat, a commercial dentin
      desensitizing agent, was also evaluated for its effect on reducing liquid flow
      through the dentin. The scanning electron microscopy images showed that the HA
      particles were successfully deposited onto the dentin and solidly into the dentin
      tubules. The permeability of dentin after application of the HA films was
      significantly lower than that following application of MS-coat. This study showed
      the potential clinical application of PJD techniques in desensitizing dentin
      hypersensitivity.

PMID- 23167476
TI  - Lymphoplasmacytic plaque in children: a report of two new cases with review of
      the literature.
AB  - Lymphoplasmacytic plaque in children has been proposed as a rare, emerging
      clinicopathologic entity characterized by solitary, extratruncal, asymptomatic
      papules and plaques that are typically found in healthy young Caucasian females.
      Biopsy of these lesions reveals a dermal lymphoplasmacytic infiltrate with or
      without epithelioid granulomas. Two unique patients with lymphoplasmacytic plaque
      in children are presented in this report, including a 26-month-old female with a
      lesion on her finger, who represents both the youngest described patient and the
      first documented with a finger lesion, as well as a 17-year-old young woman with
      a left thigh lesion, who represents the patient with the longest clinically and
      histopathologically observed lesion to date. These two additional patients
      corroborate the experience of lymphoplasmacytic plaque in children in the six
      previously reported cases and further expand the clinicopathologic spectrum of
      the disease. Recognition of lymphoplasmacytic plaque in children is important to
      facilitate distinction from potential differential considerations, including
      lymphoproliferative disorders and infectious conditions, particularly as the
      experience to date appears to suggest that lymphoplasmacytic plaque in children
      represent a reactive (pseudolymphomatous) condition.

PMID- 23167477
TI  - Transports of acetate and haloacetate in Burkholderia species MBA4 are operated
      by distinct systems.
AB  - BACKGROUND: Acetate is a commonly used substrate for biosynthesis while
      monochloroacetate is a structurally similar compound but toxic and inhibits cell
      metabolism by blocking the citric acid cycle. In Burkholderia species MBA4
      haloacetate was utilized as a carbon and energy source for growth. The
      degradation of haloacid was mediated by the production of an inducible
      dehalogenase. Recent studies have identified the presence of a concomitantly
      induced haloacetate-uptake activity in MBA4. This uptake activity has also been
      found to transport acetate. Since acetate transporters are commonly found in
      bacteria it is likely that haloacetate was transported by such a system in MBA4.
      RESULTS: The haloacetate-uptake activity of MBA4 was found to be induced by
      monochloroacetate (MCA) and monobromoacetate (MBA). While the acetate-uptake
      activity was also induced by MCA and MBA, other alkanoates: acetate, propionate
      and 2-monochloropropionate (2MCPA) were also inducers. Competing solute analysis
      showed that acetate and propionate interrupted the acetate- and MCA- induced
      acetate-uptake activities. While MCA, MBA, 2MCPA, and butyrate have no effect on
      acetate uptake they could significantly quenched the MCA-induced MCA-uptake
      activity. Transmembrane electrochemical potential was shown to be a driving force
      for both acetate- and MCA- transport systems. CONCLUSIONS: Here we showed that
      acetate- and MCA- uptake in Burkholderia species MBA4 are two transport systems
      that have different induction patterns and substrate specificities. It is
      envisaged that the shapes and the three dimensional structures of the solutes
      determine their recognition or exclusion by the two transport systems.

PMID- 23167478
TI  - Interventions employing mobile technology for overweight and obesity: an early
      systematic review of randomized controlled trials.
AB  - Obesity is a global epidemic with major healthcare implications and costs. Mobile
      technologies are potential interventions to promote weight loss. An early
      systematic review of this rapidly growing area of research was conducted.
      Electronic databases were searched for articles published between January 1998
      and October 2011. Data sources included Medline, Embase and the Cochrane Central
      Register of Controlled Trials. Ongoing research was searched for using clinical
      trials databases and registers. Out of 174 articles retrieved, 21 met the
      inclusion criteria of randomized controlled trials (RCTs) on mobile technology
      interventions facilitating weight loss in overweight and obese adults with any
      other comparator. A narrative synthesis was undertaken. Seven articles were
      included and appraised using the Cochrane risk of bias tool: four presented a low
      risk of bias and three presented a high risk of bias. There is consistent strong
      evidence across the included multiple high-quality RCTs that weight loss occurs
      in the short-term because of mobile technology interventions, with moderate
      evidence for the medium-term. Recommendations for improving the reporting and
      quality of future trials are made including reporting weight loss in percent to
      meet clinical standards, and including features such as long-term follow-up, cost
      effectiveness and patient acceptability. 

PMID- 23167479
TI  - Limited predictive power of hospitalization variables for long-term cognitive
      prognosis in adult patients with severe traumatic brain injury.
AB  - OBJECTIVES: Traumatic brain injury (TBI) is a main cause of mortality and
      morbidity. Association studies between hospitalization variables and cognitive
      impairment after TBI are frequently retrospective, including non-consecutive
      patients showing variable degrees of TBI severity, and poor management of missing
      (drop out) cases. METHODS: We assessed prospectively the demographic and
      hospitalization variables of 234 consecutive patients with severe TBI (admission
      Glasgow Coma Scale [GCS] <=8) and determined their independent association with
      cognitive performance in a representative sample (n = 46) of surviving patients
      (n = 172) evaluated 3 (+/-1.8) years after hospitalization. RESULTS: In all, 85%
      of patients were male and the mean age was 34 (SD +/-13) years. The education
      level was 9 (+/-4.7) years. As expected, education and age showed a moderately to
      strong linear relationship with the cognitive performance in 14 of 15
      neuropsychological tests (R coefficient = 0.6-0.8). The cognitive test scores
      were not independently associated with gender, admission GCS, associated trauma,
      and Marshal CT classification. Admission-elevated blood glucose levels and the
      presence of sub-arachnoid haemorrhage were independently associated with lower
      scores on Rey Auditory Verbal Learning retention and Logical Memory-I tests,
      respectively. CONCLUSIONS: After correction for education and age distribution,
      the variables that are commonly associated with mortality or Glasgow Outcome
      Scale including admission pupils' examination, Marshal CT Classification, GCS,
      and serum glucose showed a limited predictive power for long-term cognitive
      prognosis. Identification of clinical, radiological, and laboratory variables as
      well as new biomarkers independently associated with cognitive outcome remains an
      important challenge for further work involving severe TBI patients.

PMID- 23167480
TI  - Extremely low birthweight infants: how neonatal intensive care unit teams can
      reduce postnatal malnutrition and prevent growth retardation.
AB  - AIM: To evaluate the impact of an improved nutritional policy for extremely low
      birthweight (ELBW) infants on nutritional deficits and postnatal growth. METHOD:
      We compared two groups of 37 ELBW infants, born before and after the introduction
      of an improved nutritional policy in April 2006. Group A (born 2005 to early
      2006) and group B (born 2009) stayed in a French neonatal intensive care unit
      (NICU) for at least 7 weeks. Optimal energy and protein intakes were 120 and 3.5
      g/kg/day, respectively, and used to calculate cumulative deficits. Delta z-scores
      for weight, length and head circumference were calculated between birth and 36
      weeks of postmenstrual age (PMA). The improved nutritional policy focused on
      earlier and higher parenteral intake of lipids and proteins, earlier and higher
      human milk fortification and earlier transition to preterm formula. RESULTS: The
      two groups did not differ in gestational age and birthweight. However, protein
      and energy deficits were significantly reduced in group B. Between birth and 36
      weeks of PMA, delta z-scores were significantly reduced for length (p = 0.012)
      but not for weight (p = 0.09) or head circumference (p = 0.83). CONCLUSION:
      Higher parenteral intake and close attention to enteral feeding reduced
      nutritional deficits and linear growth restriction in infants admitted to a
      French NICU.

PMID- 23167482
TI  - Angstrom-scale distance dependence of antenna-enhanced vibrational signals.
AB  - The resonantly enhanced near-field of micrometer-sized gold antennas has been
      probed with Angstrom-scale resolution. In situ surface-enhanced infrared
      spectroscopic vibrational signals of carbon monoxide (CO) layers cold-condensed
      on the antennas in ultrahigh-vacuum conditions are compared to the signals of CO
      layers with corresponding thicknesses on a flat gold surface. Vibrational signals
      of CO as well as the shift of the plasmonic resonance frequency were used to
      analyze the distance dependence of the near-field. The signal enhancement induced
      by the antennas not only decays monotonically from the surface but, in contrast
      to classical near-field models, shows a maximum between 10 and 15 A and decays
      also toward the surface of the antenna. This effect is attributed to the spill
      out of the electron wave function, as expected from quantum mechanical
      calculations.

PMID- 23167483
TI  - Introduction to the special issue on aging and end of life.

PMID- 23167481
TI  - Protocol for "Seal or Varnish?" (SoV) trial: a randomised controlled trial to
      measure the relative cost and effectiveness of pit and fissure sealants and
      fluoride varnish in preventing dental decay.
AB  - BACKGROUND: Dental caries remains a significant public health problem, prevalence
      being linked to social and economic deprivation. Occlusal surfaces of first
      permanent molars are the most susceptible site in the developing permanent
      dentition. Cochrane reviews have shown pit and fissure sealants (PFS) and
      fluoride varnish (FV) to be effective over no intervention in preventing caries.
      However, the comparative cost and effectiveness of these treatments is uncertain.
      The primary aim of the trial described in this protocol is to compare the
      clinical effectiveness of PFS and FV in preventing dental caries in first
      permanent molars in 6-7 year-olds. Secondary aims include: establishing the costs
      and the relative cost-effectiveness of PFS and FV delivered in a community/school
      setting; examining the impact of PFS and FV on children and their parents/carers
      in terms of quality of life/treatment acceptability measures; and examining the
      implementation of treatment in a community setting. METHODS/DESIGN: The trial
      design comprises a randomised, assessor-blinded, two-arm, parallel group trial in
      6-7 year old schoolchildren. Clinical procedures and assessments will be
      performed at 66 primary schools, in deprived areas in South Wales. Treatments
      will be delivered via a mobile dental clinic. In total, 920 children will be
      recruited (460 per trial arm). At baseline and annually for 36 months dental
      caries will be recorded using the International Caries Detection and Assessment
      System (ICDAS) by trained and calibrated dentists. PFS and FV will be applied by
      trained dental hygienists. The FV will be applied at baseline, 6, 12, 18, 24 and
      30 months. The PFS will be applied at baseline and re-examined at 6, 12, 18, 24,
      and 30 months, and will be re-applied if the existing sealant has become
      detached/is insufficient. The economic analysis will estimate the costs of
      providing the PFS versus FV. The process evaluation will assess implementation
      and acceptability through acceptability scales, a schools questionnaire and
      interviews with children, parents, dentists, dental nurses and school staff. The
      primary outcome measure will be the proportion of children developing new caries
      on any one of up to four treated first permanent molars. DISCUSSION: The
      objectives of this study have been identified by the National Institute for
      Health Research as one of importance to the National Health Service in the UK.
      The results of this trial will provide guidance on which of these technologies
      should be adopted for the prevention of dental decay in the most susceptible
      tooth-surface in the most at risk children. TRIAL REGISTRATIONS: ISRCTN ref:
      ISRCTN17029222 EudraCT: 2010-023476-23 UKCRN ref: 9273.

PMID- 23167485
TI  - A comparison of the prevalence of chronic disease among people with and without
      intellectual disability.
AB  - Some studies have reported the presence of health disparities in people with
      intellectual disability. This study compared the prevalence of chronic health
      conditions between people with and without intellectual disability (ID). Health
      related data for 791 people with ID were collected through a province-wide mail
      survey in Quebec, Canada. The distribution of chronic health conditions reported
      was compared to the data on the health status of the general population. People
      with ID had higher reported rates of heart disease and thyroid disorder than the
      general population. We also found that people with ID were less likely to report
      suffering from arthritis, migraines, back or spinal pain, and food allergies.
      Significant health differences were found when the ID sample was stratified by
      etiology (i.e., Down syndrome) and severity of intellectual deficits. We discuss
      these results and the need for future research to understand the differences
      found in the health status of people with ID.

PMID- 23167484
TI  - Prevalence of falls and risk factors in adults with intellectual disability.
AB  - The purpose of this study was to examine the prevalence of falls and risk factors
      for falls in 1,515 adults (>= 18 years) with intellectual disability using
      baseline data from the Longitudinal Health and Intellectual Disability Study.
      Nearly 25% of adults from the study were reported to have had one or more falls
      in the past 12 months. The prevalence of falls increased with advancing age. A
      series of univariate and multivariate logistic regressions were performed to
      identify risk factors for falls in the full sample and in subsamples. The risk
      factors for falls in adults with intellectual disability are being female, having
      arthritis, having a seizure disorder, taking more than 4 medications, using
      walking aids, and having difficulty lifting/carrying greater than 10 lb.

PMID- 23167487
TI  - Into the unknown: aging with autism spectrum disorders.
AB  - Research investigation of older adults with autism spectrum disorders (ASD)
      noticeably lags behind studies of children and younger adults with ASD. This
      article reviews the current literature regarding a range of quality of life
      outcomes of aging adults with ASD. Studies that have addressed life expectancy,
      comorbid physical and mental health issues, ASD symptomatology, and social,
      residential, and vocational outcomes are reviewed. Research challenges in
      identifying older cohorts of adults with ASD are also discussed, and notable
      areas of concern are highlighted. Overall, aging with ASD does present
      challenges, but there is also evidence that positive outcomes are attainable. The
      article concludes with brief recommendations on how to optimize the aging process
      for individuals with ASD.

PMID- 23167486
TI  - Self-directed support: impact of hiring practices on adults with intellectual and
      developmental disabilities and families.
AB  - The study examined the differential experiences and outcomes for people with
      intellectual and developmental disabilities and their families receiving self
      directed services based on the type of personal support worker hired (parents,
      siblings, other relatives, friends, and agency staff). The sample consisted of
      372 participants in a self-directed waiver program who used personal assistance
      services. Results indicated that the caregiver's satisfaction with the personal
      support worker, self-efficacy in managing personal support workers, and mental
      health varied significantly based on type of personal support worker hired. Also,
      the physical health and daily choice making of the adults with disabilities
      differed significantly by type of personal support worker hired.

PMID- 23167488
TI  - Active aging for individuals with intellectual disability: meaningful community
      participation through employment, retirement, service, and volunteerism.
AB  - As individuals with intellectual and developmental disabilities become more
      engaged in community employment, it will be critical to consider how their
      employment experience changes as they age. Similar to other seniors, individuals
      will need to consider whether they want to maintain their employment, reduce
      their work commitment, or retire completely. If they do choose to retire, what
      activities will they choose to engage in, and what service or supports might be
      necessary? This article considers the issues faced by all aging workers in regard
      to retirement planning and active aging as well as specific strategies for
      individuals with intellectual and developmental disabilities to remain active and
      engaged. Recommendations for service options, policy consideration, and future
      research are also discussed.

PMID- 23167489
TI  - Unique and universal barriers: hospice care for aging adults with intellectual
      disability.
AB  - As life expectancy of people with intellectual disability (ID) has increased,
      there has been a concurrent increase in age-related illnesses and conditions
      similar to that of the general population. These circumstances result in people
      with ID dying from typical life-ending conditions, and thus, they require similar
      end-of-life services such as palliative and hospice care. Although there are
      notable barriers to hospice for all, people with ID face additional challenges in
      accessing the benefits of these services. This article presents a review of the
      literature on these issues, underscoring the multiple challenges and the
      importance of a more collaborative approach between hospice and palliative care
      workers with people with ID, their families, and other important stakeholders.

PMID- 23167491
TI  - Abundances and host relationships of chigger mites in Yunnan Province, China.
AB  - This paper reports on ectoparasitic chigger mites found on small mammals in
      Yunnan Province, southwest China. Data were accumulated from 19 investigation
      sites (counties) between 2001 and 2009. A total of 10 222 small mammal hosts were
      captured and identified; these represented 62 species, 34 genera and 11 families
      in five orders. From the body surfaces of these 10 222 hosts, a total of 92 990
      chigger mites were collected and identified microscopically. These represented
      224 species, 22 genera and three subfamilies in the family Trombiculidae
      (Trombidiformes). Small mammals were commonly found to be infested by chigger
      mites and most host species harboured several species of mite. The species
      diversity of chigger mites in Yunnan was much higher than diversities reported
      previously in other provinces of China and in other countries. A single species
      of rodent, Eothenomys miletus (Rodentia: Cricetidae), carried 111 species of
      chigger mite, thus demonstrating the highest species diversity and heaviest mite
      infestation of all recorded hosts. This diversity is exceptional compared with
      that of other ectoparasites. Of the total 224 mite species, 21 species accounted
      for 82.2% of all mites counted. Two species acting as major vectors for scrub
      typhus (tsutsugamushi disease), Leptotrombidium scutellare and Leptotrombidium
      deliense, were identified as the dominant mite species in this sample. In
      addition to these two major vectors, 12 potential or suspected vector species
      were found. Most species of chigger mite had a wide range of hosts and low host
      specificity. For example, L. scutellare parasitized 30 species of host. The low
      host specificity of chigger mites may increase their probability of encountering
      humans, as well as their transmission of scrub typhus among different hosts.
      Hierarchical clustering analysis showed that similarities between different
      chigger mite communities on the 18 main species of small mammal host did not
      accord with the taxonomic affinity of the hosts. This suggests that the
      distribution of chigger mites may be strongly influenced by the environment in
      which hosts live.

PMID- 23167492
TI  - Management of a toxic cyanobacterium bloom (Planktothrix rubescens) affecting an
      Italian drinking water basin: a case study.
AB  - An extraordinary bloom of Planktothrix rubescens, which can produce microcystins
      (MCs), was observed in early 2009 in the Occhito basin, used even as a source of
      drinking water in Southern Italy. Several activities, coordinated by a task
      force, were implemented to assess and manage the risk associated to drinking
      water contaminated by cyanobacteria. Main actions were: evaluation of analytical
      protocols for screening and confirmatory purpose, monitoring the drinking water
      supply chain, training of operators, a dedicated web site for risk communication.
      ELISA assay was considered suitable for health authorities as screening method
      for MCs and to optimize frequency of sampling according to alert levels, and as
      internal control for the water supplier. A liquid chromatography-tandem mass
      spectrometric method able to quantify 9 MCs was optimized with the aim of
      supporting health authorities in a comprehensive risk evaluation based on the
      relative toxicity of different congeners. Short, medium, and long-term corrective
      actions were implemented to mitigate the health risk. Preoxidation with chlorine
      dioxide followed by flocculation and settling have been shown to be effective in
      removing MCs in the water treatment plant. Over two years, despite the high
      levels of cyanobacteria (up to 160 * 10(6) cells/L) and MCs (28.4 MUg/L)
      initially reached in surface waters, the drinking water distribution was never
      limited.

PMID- 23167493
TI  - Investigation of human parvovirus B19 occurrence and genetic variability in
      different leukaemia entities.
AB  - Human parvovirus B19V (B19V) has been associated with various haematological
      disorders, but data on its prevalence in leukaemia are scarce. In this cross
      sectional study, we investigated patients in Sao Paulo, Brazil with leukaemia to
      determine the molecular frequency of B19 variants and characterize the viral
      genetic variability by partial and complete sequencing of the coding of non
      structural protein 1 (NS1)/viral capsid proteins 1 and 2 (VP1/VP2). The presence
      of B19V infections was investigated by PCR amplification of the viral NS1 gene
      fragment and confirmed by sequencing analysis. The NS1/VP1/VP2 and partially
      larger gene fragments of the NS1-positive samples were determined by overlapping
      nested PCR and direct sequencing results. The B19V NS1 was detected in 40 (16%)
      of 249 bone marrow samples including 12/78 (15.4%) acute lymphoblastic leukaemia,
      25/155 (16.1%) acute myeloid leukaemia and 3/16 (18.7%) chronic myeloid leukaemia
      samples. Of the 40 participants, 25 (62.5%) were infected with genotype 1a and 15
      (37.5%) with genotype 3b. The phylogenetic analysis of other regions revealed
      that 12/40 (30%) of the patients with leukaemia were co-infected with genotypes
      1a and 3b. In addition, a new B19V intergenotypic recombinant (1a/3b) and an NS1
      non-recombinant genotype 1a were detected in one patient. Our findings
      demonstrated a relatively high prevalence of B19V monoinfections and dual
      infections and provide, for the first time, evidence of inter-genotypic
      recombination in adults with leukaemia that may contribute to the genetic
      diversity of B19V and may also be a source of new emerging viral strains with
      future implications for diagnosis, therapy and efficient vaccine development.

PMID- 23167494
TI  - An anthraquinone scaffold for putative, two-face Bim BH3 alpha-helix mimic.
AB  - Bim BH3 peptide features an alpha-helix with hotspot residues on multiple faces.
      Compound 5 (6-bromo-2,3-dihydroxyanthracene-9,10-dione), which adopts a rigid
      plan amphipathic conformation, was designed and evaluated as a scaffold to mimic
      two faces of Bim alpha-helix. It reproduced the functionalities of both D67 and
      I65 on two opposing helical sides. Moreover, it maintained the two-faced binding
      mode during further evolution. A putative BH3 alpha-helix mimic and nanomolar Bcl
      2/Mcl-1 dual inhibitor, 6, was obtained based on the structure of 5.

PMID- 23167495
TI  - Proinflammatory cytokines contribute to development and function of regulatory T
      cells in type 1 diabetes.
AB  - Type 1 diabetes is caused by immune-mediated loss of pancreatic beta cells. It
      has been proposed that inflammatory cytokines play a role in killing beta cells.
      Expression of interleukin (IL)-1 and tumor necrosis factor (TNF-alpha) has been
      detected in islets from patients with type 1 diabetes, and these cytokines can
      induce beta cell death in vitro. We produced nonobese diabetic (NOD) mice lacking
      receptors for these cytokines. Islets from mice lacking IL-1RI or TNFR1 were
      killed when transplanted into wild-type NOD mice, suggesting that cytokine action
      on beta cells is not required for killing. Mice lacking TNFR1 did not develop
      diabetes, and mice lacking IL-1R had delayed onset of diabetes, indicating a role
      for these cytokines in disease development. TNFR1-deficient mice had an increased
      number of CD4(+) CD25(+) FoxP3(+) regulatory T cells with enhanced suppressive
      capacity. IL-1 was produced at higher levels in NOD mice and resulted in dilution
      of suppressor function of CD4(+) CD25(+) FoxP3(+) regulatory T cells. Our data
      suggest that blocking inflammatory cytokines may increase the capacity of the
      immune system to suppress type 1 diabetes through regulatory T cells.

PMID- 23167496
TI  - Solvent-induced homochirality in surface-confined low-density nanoporous
      molecular networks.
AB  - Induction of chirality in achiral monolayers has garnered considerable attention
      in the recent past not only due to its importance in chiral resolutions and
      enantioselective heterogeneous catalysis but also because of its relevance to the
      origin of homochirality in life. In this contribution, we demonstrate the
      emergence of macroscopic chirality in multicomponent supramolecular networks
      formed by achiral molecules at the interface of a chiral solvent and an achiral
      substrate. The solvent-mediated chiral induction provides a simple, efficient,
      and versatile approach for the fabrication of homochiral surfaces using achiral
      building blocks.

PMID- 23167497
TI  - Body image and psychological outcome after severe skin and soft tissue infection
      requiring intensive care.
AB  - BACKGROUND: Patients with severe skin and soft tissue infection (SSTI) requiring
      intensive care unit (ICU) stay are commonly treated with antibiotics, surgery and
      in some centers also with hyperbaric oxygen therapy. Long-term follow-up of body
      image and psychological outcome has not been described despite extensive surgery,
      potentially altered body image and subsequent psychological problems. The aim was
      to describe perceived body image and its relation to anxiety, depression and post
      traumatic stress disorder (PTSD)-related symptoms in patients with severe SSTI 1
      year after ICU stay. Specifically, we aimed to assess potential differences
      related to gender and anatomic site of infection. METHODS: Fifty patients treated
      for severe SSTI in the General ICU, Karolinska University Hospital 2008-2010
      received the body image scale (BIS), impact of event scale (IES), and hospital
      anxiety and depression scale (HADS) 1 year after ICU discharge. RESULTS:
      Abdominoperineal SSTI was associated with more body image problems than other
      anatomic sites of infection in both men and women. Generally, women reported
      higher BIS scores than men (median 9.5 vs. 3.0 of total 30, P < 0.03) indicating
      more negative body image. A substantial number of patients reported scar
      dissatisfaction (63.9%), body dissatisfaction (51.1%) and body feeling less whole
      (51.0%). BIS scores correlated with HADS anxiety (r = 0.59, P < 0.01), depression
      (r = 0.60, P < 0.01) and IES (r = 0.61, P < 0.01) scores. CONCLUSION: One year
      after severe SSTI requiring intensive care, women and patients with
      abdominoperineal SSTI reported significantly more body image problems. Negative
      body image was associated with anxiety, depression and PTSD-related symptoms.
      Specific follow-up for SSTI patients is warranted.

PMID- 23167499
TI  - Efficacy of supervised Tai Chi exercises versus conventional physical therapy
      exercises in fall prevention for frail older adults: a randomized controlled
      trial.
AB  - PURPOSE: To compare the effectiveness of supervised Tai Chi exercises versus the
      conventional physical therapy exercises in a personalized rehabilitation program
      in terms of the incidence and severity of falls in a frail older population.
      METHOD: The participants were frail older adults living in the community,
      admitted to the day hospital program in Sherbrooke, Quebec, Canada (n = 152).
      They were randomized to receive a 15-week intervention, either by supervised Tai
      Chi exercises (n = 76) or conventional physical therapy (n = 76). Fall incidence
      and severity were assessed using both the calendar technique and phone interviews
      once a month during 12 months following the end of the intervention. Other
      variables were collected at baseline to compare the two groups: age, comorbidity,
      balance, sensory interaction on balance, and self-rated health. RESULTS: Both
      interventions demonstrated a protective effect on falls but Tai Chi showed a
      greater one (RR = 0.74; 95% CI = 0.56-0.98) as compared to conventional physical
      therapy exercises. CONCLUSIONS: Supervised Tai Chi exercises as part of a
      rehabilitation program seem to be a more effective alternative to the
      conventional physical therapy exercises for this specific population.

PMID- 23167500
TI  - Chikungunya virus and the mosquito vector Aedes aegypti in New Caledonia (South
      Pacific Region).
AB  - Chikungunya virus (CHIKV) is transmitted to humans through the bite of Aedes
      mosquitoes. During the 2005-2006 epidemic that occurred in the Indian Ocean
      Islands, a viral strain harboring a substitution of an alanine to valine at
      position 226 (E1-A226V) of the E1 glycoprotein enhanced the transmissibility of
      CHIKV by Aedes albopictus. In March 2011, autochthonous transmission of CHIKV was
      reported in New Caledonia (NC), an island located in the southwest Pacific Ocean.
      This was the first report of local chikungunya (CHIK) transmission in this region
      of the world. Phylogenetic analysis based on the complete genome demonstrated
      that the CHIKV-NC strain isolated from the first autochthonous human case belongs
      to the Asian lineage. This is consistent with the Indonesian origin of CHIK cases
      previously imported and detected. Thus the CHIKV-NC does not present a valine
      substitution at position E1-226. In New Caledonia, the putative vector of CHIKV
      is Aedes aegypti, since no other potential vector has ever been described. For
      example, A. albopictus is not found in NC. Vector competence experiments showed
      that A. aegypti from New Caledonia was able to transmit, as early as 3 days post
      infection, two CHIKV strains: CHIKV-NC belonging to the Asian lineage, and CHIKV
      RE from Reunion Island harboring the E1-A226V mutation. Thus the extrinsic
      incubation period of both CHIKV strains in this vector species could be
      considered to be quite short. These results illustrate the threat of the spread
      of CHIKV in the South Pacific region. From February to June 2011 (the end of the
      alert), only 33 cases were detected. Implementation of drastic vector control
      measures and the occurrence of the cold season probably helped to limit the
      extent of the outbreak, but other factors may have also been involved and are
      discussed.

PMID- 23167501
TI  - Seroprevalence of tick-borne infections in military working dogs in the Republic
      of Korea.
AB  - In this study we endeavored to determine the seroprevalence of tick-borne
      infections in the military working dog (MWD) population in the Republic of Korea
      (ROK). Our sample population consisted of 182 serum samples from MWDs for 3
      different years (1996, 2002, and 2007). In addition, 63 whole blood samples from
      2007 were available for polymerase chain reaction (PCR). Serum samples were
      evaluated by a commercially available enzyme-linked immunosorbent assay (ELISA)
      and immunofluorescence assay (IFA) for Ehrlichia canis and Anaplasma
      phagocytophilum, and by ELISA only for Borrelia burgdorferi. PCR amplification of
      DNA was performed to screen for Ehrlichia canis, E. chaffeensis, E. ewingii,
      Anaplasma phagocytophilum, A. platys, Borrelia burgdorferi, and Rickettsia
      rickettsii, as well as Babesia and Theileria species using previously published
      primers and probes. A total of 56 (30.8%) MWDs were positive by at least one
      serologic test. Seroprevalences for Anaplasma and Ehrlichia were 4.4% and 0.6%
      based on the ELISA, and 24.7% and 22.5% based on the IFA, respectively. ELISA
      testing for Borrelia yielded 2 (1.1%) positive results. In parallel testing using
      both the ELISA and IFA tests, the percentages of dogs with one or more positive
      results were 34.1%, 25.9%, and 28.4%, for 1996, 2002, and 2007, respectively.
      There was no significant differences in seroprevalence based on location, year,
      breed, or sex of the MWD. There was poor agreement between IFA and ELISA test
      results. No MWD sample had a positive PCR result. MWDs stationed in Korea had
      serologic evidence of exposure to several tick-borne pathogens, but PCR testing
      did not identify any active infections.

PMID- 23167502
TI  - Easily reducible materials from the reactions of diselenopheno[3,2-b:2',3'
      d]pyrrole and dithieno[3,2-b:2',3'-d]pyrrole with tetracyanoethylene.
AB  - A new core, 4H-diselenopheno[3,2-b:2',3'-d]pyrrole (DSP), was reacted with
      tetracyanoethylene, and three products, mono-tricyanovinyl, bis-tricyanovinyl,
      and quinoidal, were isolated and compared with the respective 4H-dithieno[3,2
      b:2',3'-d]pyrrole (DTP) derivatives using cyclic voltammetry, UV-vis absorption,
      and differential scanning calorimetry analyses. Organic field-effect transistors
      were fabricated using solution-processed films, and only one derivative, bis
      tricyanovinyl-DSP, exhibited transistor behavior with MU(e) reaching 8.7 * 10(-4)
      cm(2)/V.s. This enhancement of the electron-transporting properties in comparison
      with DTP derivative is attributed to stronger LUMO-LUMO interaction due to a
      larger size of selenium atom, which in the case of the bis-tricyanovinyl
      derivative, has wave function density on the chalcogen.

PMID- 23167503
TI  - Clinical significance of c.7544-7545 delCT NOTCH1 mutation in chronic lymphocytic
      leukaemia.

PMID- 23167505
TI  - Molecular testing of leukemia cutis.

PMID- 23167504
TI  - Correlation of local effects of DNA sequence and position of beta-alanine inserts
      with polyamide-DNA complex binding affinities and kinetics.
AB  - To improve our understanding of the effects of beta-alanine (beta) substitution
      and the number of heterocycles on DNA binding affinity and selectivity, we
      investigated the interactions of an eight-ring hairpin polyamide (PA) and two
      beta derivatives as well as a six-heterocycle analogue with their cognate DNA
      sequence, 5'-TGGCTT-3'. Binding selectivity and the effects of beta have been
      investigated with the cognate and five mutant DNAs. A set of powerful and
      complementary methods have been employed for both energetic and structural
      evaluations: UV melting, biosensor surface plasmon resonance, isothermal
      titration calorimetry, circular dichroism, and a DNA ligation ladder global
      structure assay. The reduced number of heterocycles in the six-ring PA weakens
      the binding affinity; however, the smaller PA aggregates significantly less than
      the larger PAs and allows us to obtain the binding thermodynamics. The PA-DNA
      binding enthalpy is large and negative with a large negative DeltaC(p) and is the
      primary driving component of the Gibbs free energy. The complete SPR binding
      results clearly show that beta substitutions can substantially weaken the binding
      affinity of hairpin PAs in a position-dependent manner. More importantly, the
      changes in the binding of PA to the mutant DNAs further confirm the position
      dependent effects on the PA-DNA interaction affinity. Comparison of mutant DNA
      sequences also shows a different effect in recognition of T.A versus A.T base
      pairs. The effects of DNA mutations on binding of a single PA as well as the
      effects of the position of beta substitution on binding tell a clear and very
      important story about sequence-dependent binding of PAs to DNA.

PMID- 23167507
TI  - Impact of preserved myocardial contractile function in the segments attached to
      the papillary muscles on reduction in functional mitral regurgitation.
AB  - BACKGROUND: Effectiveness of functional mitral regurgitation (FMR) in heart
      failure patients is of growing importance for patient prognosis. The purpose of
      this study was to investigate whether regional myocardial contractile function as
      assessed by tissue Doppler strain rate imaging can predict reduction in FMR
      caused by dobutamine. METHODS: Fifty-one patients with depressed left ventricular
      (LV) ejection fraction (32 +/- 9%) secondary to dilated cardiomyopathy and FMR
      underwent evaluation of effective regurgitant orifice (ERO) of FMR, mitral valve
      deformation, global LV remodeling, and regional myocardial contractile function
      assessed by longitudinal peak systolic strain rate (Ssr) in 6 mid-LV segments
      from standard apical views. We also determined the average Ssr of segments
      attached to the papillary muscles, that is, the inferior, inferolateral, and
      anterolateral segments (PM segments Ssr). Low-dose (10 MUg/kg per minute)
      dobutamine-induced reduction in ERO was compared with baseline variables.
      RESULTS: Baseline valve tenting was associated with dobutamine-induced reduction
      in ERO (r = -0.30, P < 0.05). Receiver operating characteristic curve analysis
      showed that baseline valve tenting, LV sphericity index, inferior Ssr,
      inferolateral Ssr, and PM segments Ssr were predictors of dobutamine-induced
      >=30% reduction in ERO. Importantly, only PM segments Ssr predicted dobutamine
      induced >=20% reduction in valve tenting with area under the curve of 0.67 (P <
      0.05). CONCLUSIONS: Preserved myocardial contractile function in the segments
      attached to the PMs was associated with dobutamine-induced reduction in mitral
      valve tenting and FMR, suggesting that our findings are important for improvement
      in cardiac function and FMR with medical treatment.

PMID- 23167509
TI  - Mycological studies of nail samples obtained by curettage vs. vertical
      perforation of the nail plate.

PMID- 23167508
TI  - Effect of corticosteroid withdrawal on tacrolimus and mycophenolate mofetil
      exposure in a randomized multicenter study.
AB  - As corticosteroid-sparing protocols are increasingly utilized in kidney
      transplant recipients, it is crucial to understand potential drug interactions
      between tacrolimus (TAC) and the effect of corticosteroid withdrawal as well as
      to characterize dose adjustments of mycophenolate mofetil (MMF) in this setting.
      This prospective, multicenter, randomized, double-blind study included 397
      patients who were randomized on posttransplant day 8 to receive either placebo
      (CSWD) or corticosteroid continuance (CCS). TAC trough levels at week two
      posttransplant were significantly greater in the CSWD group whereas TAC doses
      were comparable to the CCS group. This interaction was not observed in the
      African American subgroup. Higher serum creatinine and potassium levels were also
      observed in the CSWD group. MMF dose was significantly reduced in the CSWD group
      by the investigators because of decreased WBC counts, mostly outside of study
      protocol criteria, despite similar incidence of neutropenia and reported
      cytomegalovirus infection. Understanding TAC and MMF exposure in the context of
      corticosteroid-sparing protocols should allow for improved dosing of
      immunosuppressants and better management of posttransplant patients.

PMID- 23167510
TI  - Biogenesis of photosynthetic complexes in the chloroplast of Chlamydomonas
      reinhardtii requires ARSA1, a homolog of prokaryotic arsenite transporter and
      eukaryotic TRC40 for guided entry of tail-anchored proteins.
AB  - as1, for antenna size mutant 1, was obtained by insertion mutagenesis of the
      unicellular green alga Chlamydomonas reinhardtii. This strain has a low
      chlorophyll content, 8% with respect to the wild type, and displays a general
      reduction in thylakoid polypeptides. The mutant was found to carry an insertion
      into a homologous gene, prokaryotic arsenite transporter (ARSA), whose yeast and
      mammal counterparts were found to be involved in the targeting of tail-anchored
      (TA) proteins to cytosol-exposed membranes, essential for several cellular
      functions. Here we present the characterization in a photosynthetic organism of
      an insertion mutant in an ARSA-homolog gene. The ARSA1 protein was found to be
      localized in the cytosol, and yet its absence in as1 leads to a small chloroplast
      and a strongly decreased chlorophyll content per cell. ARSA1 appears to be
      required for optimal biogenesis of photosynthetic complexes because of its
      involvement in the accumulation of TOC34, an essential component of the outer
      chloroplast membrane translocon (TOC) complex, which, in turn, catalyzes the
      import of nucleus-encoded precursor polypeptides into the chloroplast.
      Remarkably, the effect of the mutation appears to be restricted to biogenesis of
      chlorophyll-binding polypeptides and is not compensated by the other ARSA homolog
      encoded by the C. reinhardtii genome, implying a non-redundant function.

PMID- 23167511
TI  - Smoking cessation in pregnant women with mental disorders: a cohort and nested
      qualitative study.
AB  - OBJECTIVE: To investigate whether 1) pregnant smokers with mental disorders are
      less likely to accept referrals to smoking cessation services compared with
      pregnant smokers without disorders; 2) they experience specific barriers to
      smoking cessation. DESIGN: Cohort study supplemented by cross-sectional survey
      and nested qualitative study. SETTING: Three maternity services, London, UK.
      POPULATION: Pregnant smokers with and without mental disorders. METHODS: Case
      notes were examined on a cohort of 400 consecutive pregnant smokers; data were
      triangulated with routinely collected data on 845 pregnant smokers at two other
      sites; 27 pregnant smokers were interviewed using qualitative methods. MAIN
      OUTCOME MEASURES: Acceptance of referral to smoking cessation services; perceived
      barriers to quitting. RESULTS: Pregnant smokers with a mental disorder recorded
      by midwives were one-quarter of the cohort (97, 23%), were more likely to accept
      referral to smoking cessation services (69% versus 56%, adjusted odds ratio 1.70,
      95% confidence interval 1.03-2.79), but more likely to still smoke at delivery
      (69% versus 56%, adjusted odds ratio 2.63, 95% confidence interval 1.41-4.92).
      Discussion about smoking was documented in 7.7% of subsequent antenatal visits in
      women with or without mental disorders. Pregnant smokers with diagnosed mental
      disorders reported that they and health practitioners did not prioritise smoking
      advice because of concern about adversely impacting mental health. CONCLUSIONS:
      Pregnant women with mental disorders appear more motivated, yet find it more
      difficult, to stop smoking. Prioritisation of mental health over smoking may
      therefore lead to increasing health inequality for this group. Research into
      effective smoking cessation interventions is required for those with mental
      disorders.

PMID- 23167512
TI  - Ceftaroline fosamil: a new cephalosporin active against resistant Gram-positive
      organisms including MRSA.
AB  - The growing prevalence of resistant Gram-positive pathogens such as methicillin
      resistant Staphylococcus aureus continues to pose a dilemma to clinicians. With
      strains developing reduced susceptibility to vancomycin, effective and well
      tolerated antibiotics to combat these resistant pathogens are needed. Ceftaroline
      is a new parenteral cephalosporin that has been available in the USA for almost 2
      years. Similar to other cephalosporins, it is well tolerated with mostly mild
      adverse events; however, compared with existing parenteral cephalosporins,
      ceftaroline has the unique attribute of being bactericidal against resistant Gram
      positive aerobes including both hospital- and community-acquired methicillin
      resistant S. aureus, S. aureus strains with reduced susceptibility or complete
      resistance to vancomycin, and resistant Streptococcus pneumoniae including
      multidrug-resistant strains. Current indications in the USA and Europe include
      treatment of adults with complicated skin, skin-structure infections and
      community-acquired pneumonia. This paper will review the properties of
      ceftaroline, its spectrum of activity, clinical use, safety profile and future
      role.

PMID- 23167513
TI  - Synergies between RNA degradation and trans-translation in Streptococcus
      pneumoniae: cross regulation and co-transcription of RNase R and SmpB.
AB  - BACKGROUND: Ribonuclease R (RNase R) is an exoribonuclease that recognizes and
      degrades a wide range of RNA molecules. It is a stress-induced protein shown to
      be important for the establishment of virulence in several pathogenic bacteria.
      RNase R has also been implicated in the trans-translation process. Transfer
      messenger RNA (tmRNA/SsrA RNA) and SmpB are the main effectors of trans
      translation, an RNA and protein quality control system that resolves challenges
      associated with stalled ribosomes on non-stop mRNAs. Trans-translation has also
      been associated with deficiencies in stress-response mechanisms and
      pathogenicity. RESULTS: In this work we study the expression of RNase R in the
      human pathogen Streptococcus pneumoniae and analyse the interplay of this enzyme
      with the main components of the trans-translation machinery (SmpB and
      tmRNA/SsrA). We show that RNase R is induced after a 37 degrees C to 15 degrees C
      temperature downshift and that its levels are dependent on SmpB. On the other
      hand, our results revealed a strong accumulation of the smpB transcript in the
      absence of RNase R at 15 degrees C. Transcriptional analysis of the S. pneumoniae
      rnr gene demonstrated that it is co-transcribed with the flanking genes, secG and
      smpB. Transcription of these genes is driven from a promoter upstream of secG and
      the transcript is processed to yield mature independent mRNAs. This genetic
      organization seems to be a common feature of Gram positive bacteria, and the
      biological significance of this gene cluster is further discussed. CONCLUSIONS:
      This study unravels an additional contribution of RNase R to the trans
      translation system by demonstrating that smpB is regulated by this
      exoribonuclease. RNase R in turn, is shown to be under the control of SmpB. These
      proteins are therefore mutually dependent and cross-regulated. The data presented
      here shed light on the interactions between RNase R, trans-translation and cold
      shock response in an important human pathogen.

PMID- 23167514
TI  - Utility of quantitative 18 F-fluorodeoxyglucose uptake measurement to identify
      occult tonsillar carcinoma in patients with cervical metastasis of unknown
      primary tumours: a retrospective case-control study.
AB  - OBJECTIVES: Due to relatively high (18) F-fluorodeoxyglucose accumulation in the
      tonsillar region, the detection of occult tonsillar cancers by (18) F
      fluorodeoxyglucose positron emission tomography/computerised tomography remains
      controversial. Therefore, we assessed the usefulness of quantitative tonsil (18)
      F-fluorodeoxyglucose uptake in identifying occult tonsillar squamous cell
      carcinoma. DESIGN: A case-control study of retrospective cohorts. SETTING:
      University Teaching Hospital. MAIN OUTCOME MEASURES: We assessed all patients
      diagnosed with tonsillar cancers or cervical lymph node metastasis of unknown
      primary tumours between 2005 and 2010 who underwent (18) F-fluorodeoxyglucose
      positron emission tomography/computerised tomography. The subjects were grouped
      into A (apparent early pT-stage tonsillar squamous cell carcinoma; n = 27), B
      (occult tonsillar squamous cell carcinoma, primary tumours were found by surgery;
      n = 21), C (cervical metastasis of unknown primary tumour, primary tumours were
      not found by surgery and for follow-up; n = 16) and D (33 healthy controls).
      Tonsillar maximum standardised uptake values were bilaterally measured and
      compared between groups. RESULTS: The sensitivity and specificity of qualitative
      assessment of (18) F-fluorodeoxyglucose positron emission tomography/computerised
      tomography for detection of occult tonsillar cancers were 67% and 69%,
      respectively. Mean maximum standardised uptake values of tonsils with cancer were
      11.19 +/- 5.46 in group A and 8.12 +/- 4.52 in group B, which were significantly
      higher than that of group C (4.62 +/- 1.76) or group D (4.57 +/- 1.62) (P <
      0.01). The mean maximum standardised uptake value differences of groups A (6.35)
      and B (3.11) were significantly greater than those of groups C (0.32) and D
      (0.59) (P < 0.01). Similarly, the mean maximum standardised uptake value ratios
      of groups A (2.47) and B (1.73) were significantly greater than those of groups C
      (1.06) and D (1.16) (P < 0.01). CONCLUSION: (18) F-fluorodeoxyglucose positron
      emission tomography/computerised tomography with tonsil SUVmax measurement is
      useful to identify occult tonsillar squamous cell carcinoma.

PMID- 23167515
TI  - Development and validation of a ReaxFF reactive force field for Fe/Al/Ni alloys:
      molecular dynamics study of elastic constants, diffusion, and segregation.
AB  - We have developed a ReaxFF force field for Fe/Al/Ni binary alloys based on
      quantum mechanical (QM) calculations. In addition to the various bulk phases of
      the binary alloys, the (100), (110) and (111) surface energies and adatom binding
      energies were included in the training set for the force field parametrization of
      the Fe/Al/Ni binary alloys. To validate these optimized force fields, we studied
      (i) elastic constants of the binary alloys at finite temperatures, (ii)
      diffusivity of alloy components in Al/Ni alloy, and (iii) segregation on the
      binary alloy surfaces. First, we calculated linear elastic constants of FeAl,
      FeNi(3), and Ni(3)Al in the temperature range 300 to 1100 K. The temperature
      dependences of the elastic constants of these three alloys, showing a decrease in
      C(11), C(12), and C(44) as temperature increases, were in good agreement with the
      experimental results. We also performed ReaxFF molecular dynamics (MD)
      simulations for Al or Ni diffusion in the system modeled as Al/Ni mixed layers
      with the linear composition gradients. At 1000 K, Al diffusivity at the pure Al
      end was 2 orders of magnitude larger than that in the Al trace layers, probably
      explaining the nature of different diffusion behavior between molten metals and
      alloys. However, the diffusivity of Ni at the pure Ni end was only slightly
      larger than that in the Ni trace layers at the system temperature much lower than
      the melting temperature of Ni. Third, we investigated the surface segregation in
      L1(2)-Fe(3)Al, Fe(3)Ni, and Ni(3)Al clusters at high temperature (2500 K). From
      the analysis of composition distribution of the alloy components from the bulk to
      the surface layer, it was found that the degree of segregation depended on the
      chemical composition of the alloy. Al surface segregation occurred most strongly
      in Fe(3)Al, whereas it occurred most weakly in Ni(3)Al. These results may support
      the segregation mechanism that surface segregation results from the interplay
      between the energetic stability of the ordered bulk phase and the surface
      reconstruction. In addition, the surface segregation induced the depletion layers
      of segregating metal species (Al in Fe(3)Al and Ni(3)Al, and Ni in Fe(3)Ni) next
      to the segregation layers. These simulation results qualitatively agreed with
      early experimental observations of segregation in Fe/Al/Ni binary alloys.

PMID- 23167516
TI  - Effects of nutritional supplementation combined with conventional pulmonary
      rehabilitation in muscle-wasted chronic obstructive pulmonary disease: a
      prospective, randomized and controlled study.
AB  - BACKGROUND AND OBJECTIVE: Nutritional depletion in chronic obstructive pulmonary
      disease (COPD) adversely affects health status and mortality. We aimed to
      evaluate the effects of nutritional supplementation (NS) with pulmonary
      rehabilitation (PR) on body composition, mid-thigh cross-sectional area (CSA),
      dyspnoea, exercise capacity, health-related quality of life, anxiety and
      depression in advanced COPD patients. METHODS: Forty-six patients were randomized
      to PR and nutritional support (PRNS), PR or the control group. Dyspnoea was
      measured with Medical Research Council and BORG scales. Exercise capacity was
      measured through 6-min walk test and shuttle tests; health-related quality of
      life was assessed with St. George's Respiratory Questionnaire. Psychological
      status was measured with Hospital Anxiety and Depression Scale. Body weight and
      body mass indexes (BMI) were also evaluated. Fat-free mass was measured through
      bioelectrical impedance analyser. The CSA of quadriceps was calculated in mid
      level of the thigh with magnetic resonance imaging. RESULTS: Dyspnoea and total
      scores of St. George's Respiratory Questionnaire improved in both groups (P <
      0.05). Six-minute walk test and incremental shuttle walk test distances in PRNS
      and PR patients increased significantly as (62.6 +/- 42.4 m, 43.3 +/- 59.2 m,
      both P = 0.001; and 63.3 +/- 70.1 m and 69.3 +/- 69.7 m, both P = 0.001).
      Although anxiety improved in both groups (P < 0.05), there was no change in
      depression. Body weight, BMI and fat-free mass index (FFMI) (1.1 +/- 0.9 kg, 0.2
      +/- 1.4 kg/m(2) and 0.6 +/- 0.5 kg/m(2), P < 0.05) in PRNS, whereas body weight
      and FFMI (0.6 +/- 0.7 kg, 0.1 +/- 0.6 kg/m(2) P < 0.05) increased in PR after the
      intervention. There was a significant increase in mid-thigh CSA (2.5 +/- 4.1
      cm(2)) only in PRNS (P = 0.04). CONCLUSION: The combination of NS with PR
      resulted in improvements particularly in lean body mass and mid-thigh CSA. This
      study suggests combining NS with PR in reversing weight loss and muscle wasting
      in COPD.

PMID- 23167517
TI  - Evolution of the Macondo well blowout: simulating the effects of the circulation
      and synthetic dispersants on the subsea oil transport.
AB  - During the Deepwater Horizon incident, crude oil flowed into the Gulf of Mexico
      from 1522 m underwater. In an effort to prevent the oil from rising to the
      surface, synthetic dispersants were applied at the wellhead. However,
      uncertainties in the formation of oil droplets and difficulties in measuring
      their size in the water column, complicated further assessment of the potential
      effect of the dispersant on the subsea-to-surface oil partition. We adapted a
      coupled hydrodynamic and stochastic buoyant particle-tracking model to the
      transport and fate of hydrocarbon fractions and simulated the far-field transport
      of the oil from the intrusion depth. The evaluated model represented a baseline
      for numerical experiments where we varied the distributions of particle sizes and
      thus oil mass. The experiments allowed to quantify the relative effects of
      chemical dispersion, vertical currents, and inertial buoyancy motion on oil rise
      velocities. We present a plausible model scenario, where some oil is trapped at
      depth through shear emulsification due to the particular conditions of the
      Macondo blowout. Assuming effective mixing of the synthetic dispersants at the
      wellhead, the model indicates that the submerged oil mass is shifted deeper,
      decreasing only marginally the amount of oil surfacing. In this scenario, the oil
      rises slowly to the surface or stays immersed. This suggests that other
      mechanisms may have contributed to the rapid surfacing of oil-gas mixture
      observed initially. The study also reveals local topographic and hydrodynamic
      processes that influence the oil transport in eddies and multiple layers. This
      numerical approach provides novel insights on oil transport mechanisms from deep
      blowouts and on gauging the subsea use of synthetic dispersant in mitigating
      coastal damage.

PMID- 23167518
TI  - Eyes on new product development.

PMID- 23167519
TI  - Efficiency of molar distalization associated with second and third molar eruption
      stage.
AB  - OBJECTIVE: To evaluate the efficiency of molar distalization associated with the
      second and third molar eruption stage. MATERIALS AND METHODS: A systematic
      computerized database search was conducted using several databases. Adaptations
      of the terms molar distalization and distalizing appliances were used. The
      reference lists of all the selected articles were also searched for any potential
      articles that might have been missed in the electronic search. The data provided
      in the selected publications were grouped and analyzed in terms of molar
      distalization with respect to various eruption stages of maxillary second and
      third molars. RESULTS: Out of the 13 initially identified articles only four
      fulfilled the final selection criteria. Three of the four studies showed no
      statistical significance in linear molar distalization based on the eruptive
      stage of the second and/or third molars, while one study found that the amount of
      distal movement of the first molars was significantly greater in the group with
      unerupted second molars. Only one study found that the amount of molar tipping
      that occurred as a result of distalization was related to the eruption stage of
      the maxillary molars. Similarly, three of the four studies found that molar
      distalization time was not significantly affected by eruption of the second or
      third molars. CONCLUSION: The effect of maxillary second and third molar eruption
      stage on molar distalization-both linear and angular distalization-appears to be
      minimal. This conclusion is only based on low-level of evidence clinical trials.
      The large variability in the outcomes should be considered clinically.

PMID- 23167523
TI  - JGH and me: a long and winding road-reflections of an outgoing Editor-in-Chief.

PMID- 23167521
TI  - Small rectal carcinoids: not always benign.

PMID- 23167522
TI  - Splanchnic vascular involvement and autoimmune pancreatitis.

PMID- 23167520
TI  - Expanding the therapeutic armamentarium of ulcerative proctitis.

PMID- 23167524
TI  - Education and imaging: hepatobiliary and pancreatic: Abernethy malformation
      congenital portocaval shunt.

PMID- 23167525
TI  - Cooperative organization in iron oxide multi-core nanoparticles potentiates their
      efficiency as heating mediators and MRI contrast agents.
AB  - In the pursuit of optimized magnetic nanostructures for diagnostic and
      therapeutic applications, the role of nanoparticle architecture has been poorly
      investigated. In this study, we demonstrate that the internal collective
      organization of multi-core iron oxide nanoparticles can modulate their magnetic
      properties in such a way as to critically enhance their hyperthermic efficiency
      and their MRI T(1) and T(2) contrast effect. Multi-core nanoparticles composed of
      maghemite cores were synthesized through a polyol approach, and subsequent
      electrostatic colloidal sorting was used to fractionate the suspensions by size
      and hence magnetic properties. We obtained stable suspensions of citrate
      stabilized nanostructures ranging from single-core 10 nm nanoparticles to multi
      core magnetically cooperative 30 nm nanoparticles. Three-dimensional oriented
      attachment of primary cores results in enhanced magnetic susceptibility and
      decreased surface disorder compared to individual cores, while preserving a
      superparamagnetic-like behavior of the multi-core structures and potentiating
      thermal losses. Exchange coupling in the multi-core nanoparticles modifies the
      dynamics of the magnetic moment in such a way that both the longitudinal and
      transverse NMR relaxivities are also enhanced. Long-term MRI detection of tumor
      cells and their efficient destruction by magnetic hyperthermia can be achieved
      thanks to a facile and nontoxic cell uptake of these iron oxide nanostructures.
      This study proves for the first time that cooperative magnetic behavior within
      highly crystalline iron oxide superparamagnetic multi-core nanoparticles can
      improve simultaneously therapeutic and diagnosis effectiveness over existing
      nanostructures, while preserving biocompatibility.

PMID- 23167526
TI  - Garcinia  xanthones as orally active antitumor agents.
AB  - Using a newly developed strategy whose key step is the regioselective
      propargylation of hydroxyxanthone substrates, 99 structurally diverse Garcinia
      natural-product-like xanthones based on gambogic acid were designed and
      synthesized and their in vitro antitumor activity was evaluated. A set of 40
      related compounds was chosen for determination of their physicochemical
      properties including polar surface area, log D7.4, aqueous solubility, and
      permeability at pH 7.4. In the light of the in vitro antitumor activity and the
      physicochemical properties, two compounds were advanced into in vivo efficacy
      experiments. The antitumor activity of compound 112, administered po, showed more
      potent in vivo oral antitumor activity than gambogic acid.

PMID- 23167527
TI  - Flexible silver nanowire meshes for high-efficiency microtextured organic-silicon
      hybrid photovoltaics.
AB  - Hybrid organic-silicon heterojunction solar cells promise a significant reduction
      on fabrication costs by avoiding energy-intensive processes. However, their
      scalability remains challenging without a low-cost transparent electrode. In this
      work, we present solution-processed silver-nanowire meshes that uniformly cover
      the microtextured surface of hybrid heterojunction solar cells to enable
      efficient carrier collection for large device area. We systematically compare the
      characteristics and device performance with long and short nanowires with an
      average length/diameter of 30 MUm/115 nm and 15 MUm/45 nm, respectively, to those
      with silver metal grids. A remarkable power conversion efficiency of 10.1% is
      achieved with a device area of 1 * 1 cm(2) under 100 mW/cm(2) of AM1.5G
      illumination for the hybrid solar cells employing long wires, which represents an
      enhancement factor of up to 36.5% compared to the metal grid counterpart. The
      high-quality nanowire network displays an excellent spatial uniformity of
      photocurrent generation via distributed nanowire meshes and low dependence on
      efficient charge transport under a high light-injection condition with increased
      device area. The capability of silver nanowires as flexible transparent
      electrodes presents a great opportunity to accelerate the mass deployment of high
      efficiency hybrid silicon photovoltaics via simple and rapid soluble processes.

PMID- 23167528
TI  - The clinical use of Kampo medicines (traditional Japanese herbal treatments) for
      controlling cancer patients' symptoms in Japan: a national cross-sectional
      survey.
AB  - BACKGROUND: Kampo medicines are traditional Japanese medicines produced from
      medicinal plants and herbs. Even though the efficacy of Kampo medicines for
      controlling cancer-related symptoms is being reported, their actual nationwide
      clinical use has not been comprehensively investigated. We aimed to investigate
      physicians' recognition of Kampo medicines and their clinical use for cancer
      patients in the field of palliative care. METHODS: A cross-sectional self
      administered anonymous questionnaire was distributed to 549 physicians working in
      palliative care teams at 388 core cancer treatment hospitals and 161 certified
      medical institutions that have palliative care units (PCUs). RESULTS: Valid
      responses were obtained from 311 physicians (response rate, 56.7%) who were
      evenly distributed throughout the country without significant geographical
      biases. Kampo medicines were prescribed for controlling cancer-related symptoms
      by 64.3% of the physicians. The symptoms treated with Kampo medicines were
      numbness/hypoesthesia (n = 99, 49.5%), constipation (n = 76, 38.0%),
      anorexia/weight loss (n = 72, 36%), muscle cramps (n = 71, 35.5%) and
      languor/fatigue (n = 64, 32.0%). Regarding open issues about prescription, 60.7%
      (n = 173) of the physicians raised the issue that the dosage forms need to be
      better devised. CONCLUSIONS: To increase the clinical use of Kampo medicines,
      more evidence from clinical studies is necessary. In addition, their mechanisms
      of action should be clarified through laboratory studies.

PMID- 23167530
TI  - Gut microbiota changes in rainbow trout, Oncorhynchus mykiss (Walbaum), during
      organic acid feed supplementation and Yersinia ruckeri infection.

PMID- 23167529
TI  - Efficacy of DEET and non-DEET-based insect repellents against bites of Simulium
      damnosum vectors of onchocerciasis.
AB  - Coping strategies including smoke screens are used against nuisance bites of
      Simulium damnosum Theobald (Diptera:Simuliidae) in onchocerciasis endemic
      communities. To find more effective alternatives, the efficacy of commercially
      available N,N-diethyl-3-methylbenzamide (DEET) products with active
      concentrations of 9.5, 13, 25, 50 and 98.1-100% and 'NO MAS,' (active component:
      para-menthane-3,8-diol and lemon grass oil) were tested at Bui-Agblekame, Ghana.
      A Latin square study design was implemented using eight groups of two vector
      collectors each, who used repellents (treatment), mineral oil or nothing each day
      until the end of the study. Flies were caught and their numbers each hour
      recorded using the standard methods for onchocerciasis transmission studies. T
      tests were used to compare the mean duration of protection and a one-way analysis
      of variance controlling for catchers and repellents was performed. Tukey's test
      was used to compare protection by repellents and mineral oil. The highest
      percentage protection was 80.8% by NO MAS and the least 42.5% by the 13% DEET
      product. The period of absolute protection was 5 h by NO MAS and 1 h by 50% DEET
      product. No significant increase in protection was offered beyond 25% active DEET
      products and no significance was observed in terms of catcher * repellent effect
      (F = 1.731, d.f. = 48, P = 0.209).

PMID- 23167531
TI  - Absorption, metabolism and excretion of darexaban (YM150), a new direct factor Xa
      inhibitor in humans.
AB  - 1. The absorption, metabolism and excretion of darexaban (YM150), a novel oral
      direct factor Xa inhibitor, were investigated after a single oral administration
      of [(14)C]darexaban maleate at a dose of 60 mg in healthy male human subjects. 2.
      [(14)C]Darexaban was rapidly absorbed, with both blood and plasma concentrations
      peaking at approximately 0.75 h post-dose. Plasma concentrations of darexaban
      glucuronide (M1), the pharmacological activity of which is equipotent to
      darexaban in vitro, also peaked at approximately 0.75 h. 3. Similar amounts of
      dosed radioactivity were excreted via faeces (51.9%) and urine (46.4%) by 168 h
      post-dose, suggesting that at least approximately half of the administered dose
      is absorbed from the gastrointestinal tract. 4. M1 was the major drug-related
      component in plasma and urine, accounting for up to 95.8% of radioactivity in
      plasma. The N-oxides of M1, a mixture of two diastereomers designated as M2 and
      M3, were also present in plasma and urine, accounting for up to 13.2% of
      radioactivity in plasma. In faeces, darexaban was the major drug-related
      component, and N-demethyl darexaban (M5) was detected as a minor metabolite. 5.
      These findings suggested that, following oral administration of darexaban in
      humans, M1 is quickly formed during first-pass metabolism via UDP
      glucuronosyltransferases, exerting its pharmacological activity in blood before
      being excreted into urine and faeces.

PMID- 23167532
TI  - Nociceptive stimuli responses at different levels of general anaesthesia and
      genetic variability.
AB  - BACKGROUND: Changes in skin conductance (SC), clinical stress score (CSS), the
      bispectral index spectroscopy (BIS) index and the variation in the BIS index may
      be used to monitor responses to nociceptive stimuli. We wanted to examine these
      methods during noxious stimulation during general anaesthesia and if the
      responses were associated with variability in genes related to pain. METHODS:
      Sixty patients, given propofol to a BIS level of 40-50, were stimulated with
      standardised tetanic electrical stimuli during propofol infusion, plasma level of
      3 MUg/ml alone, or together with remifentanil target plasma level of 3 ng/ml or
      10 ng/ml. The CSS, SC, BIS index and the variability of the BIS index were
      registered. The inter-individual variation in nociceptive responses was analysed
      for co-variation with genotypes of 89 single nucleotide polymorphisms from 23
      candidate genes. RESULTS: During tetanic stimuli, CSS and SC increased
      significantly and were attenuated with increasing level of remifentanil,
      different from the BIS index and the variation in the BIS index. Polymorphisms in
      the P-glycoprotein (ABCB1), tachykinin 1 receptor (TACR1), dopamine receptor D3
      (DRD3) and beta arrestin 2 (ARRB2) genes were associated with the co-variation in
      SC variables or CSS response or both during standardised nociceptive stimuli (P <
      0.05). Because of no corrections for multiple testing, the genetic analyses are
      explorative, and associations must be tested in further studies. CONCLUSION: This
      exploratory study suggests genes that may be tested further with relation to
      nociceptive response during anaesthesia. SC and CSS may be useful tools for
      monitoring nociceptive response during general anaesthesia.

PMID- 23167533
TI  - Importance of direct metal-pi coupling in electronic transport through conjugated
      single-molecule junctions.
AB  - We study the effects of molecular structure on the electronic transport and
      mechanical stability of single-molecule junctions formed with Au point contacts.
      Two types of linear conjugated molecular wires are compared: those functionalized
      with methylsulfide or amine aurophilic groups at (1) both or (2) only one of its
      phenyl termini. Using scanning tunneling and atomic force microscope break
      junction techniques, the conductance of mono- and difunctionalized molecular
      wires and its dependence on junction elongation and rupture forces were studied.
      Charge transport through monofunctionalized wires is observed when the molecular
      bridge is coupled through a S-Au donor-acceptor bond on one end and a relatively
      weak Au-pi interaction on the other end. For monofunctionalized molecular wires,
      junctions can be mechanically stabilized by installing a second aurophilic group
      at the meta position that, however, does not in itself contribute to a new
      conduction pathway. These results reveal the important interplay between
      electronic coupling through metal-pi interactions and quantum mechanical effects
      introduced by chemical substitution on the conjugated system. This study affords
      a strategy to deterministically tune the electrical and mechanical properties
      through molecular wires.

PMID- 23167534
TI  - Are the mental representations of people with osteoarthritis consistent with the
      International Classification of Functioning Disability and Health?
AB  - PURPOSE: This study examined whether the mental representations of people with
      osteoarthritis (OA) were consistent with the International Classification of
      Functioning Disability and Health (ICF) model. METHODS: A geographical cohort of
      202 people with OA about to have joint replacement surgery completed postal
      questionnaires. Mental representations were measured by asking participants what
      they were hoping for from their joint replacement. Two expert judges classified
      these illness representations to the main ICF constructs of Impairment (I),
      Activity Limitation (A) and Participation Restriction (P). RESULTS: There was
      strong agreement between the expert judges. There were a similar number of
      illness representations for each of the ICF constructs. The primary biomedical
      route of the ICF model was suggested by the ordering of the participants' illness
      representations i.e. I to A to P. CONCLUSIONS: The mental representations of
      people with OA were consistent with the ICF theoretical framework with all three
      ICF constructs of importance. It appeared that people with OA implicitly apply a
      biomedical causal model of disability, suggesting that treatments and
      interventions aimed at reducing impairment may only affect P indirectly, through
      A. Additionally, the methods provide a novel way of exploring the potential
      causal relationships between constructs of the ICF model.

PMID- 23167535
TI  - Low verbal ability predicts later violence in adolescent boys with serious
      conduct problems.
AB  - BACKGROUND: Delinquent adolescents are a known high-risk group for later
      criminality. Cognitive deficits correlate with adult criminality, and specific
      cognitive deficits might predict later criminality in the high-risk adolescents.
      AIMS: This study aimed to explore the neuropsychological performance and
      predictors of adult criminal offending in adolescents with severe behavioural
      problems. METHODS: Fifty-three adolescents (33 boys and 20 girls), aged 15-18
      years, residing in a reform school due to serious conduct problems, were examined
      for neuropsychological profile and psychiatric symptoms. Results were compared
      with a same-age general population control sample, and used for predicting
      criminality 5 years after the baseline testing. RESULTS: The reform school
      adolescents' neuropsychological performance was weak on many tasks, and
      especially on the verbal domain. Five years after the baseline testing, half of
      the reform school adolescents had obtained a criminal record. Males were
      overrepresented in both any criminality (75% vs. 10%) and in violent crime (50%
      vs. 5%). When cognitive variables, psychiatric symptoms and background factors
      were used as predictors for later offending, low verbal intellectual ability
      turned out to be the most significant predictor of a criminal record and
      especially a record of violent crime. CONCLUSIONS: Neurocognitive deficits,
      especially in the verbal and attention domains, are common among delinquent
      adolescents. Among males, verbal deficits are the best predictors for later
      criminal offending and violence. CLINICAL IMPLICATIONS: Assessing verbal
      abilities among adolescent population with conduct problems might prove useful as
      a screening method for inclusion in specific therapies for aggression management.

PMID- 23167536
TI  - Depressive symptoms, major depressive episodes and cognitive test performance
      what is the role of physical activity?
AB  - BACKGROUND: Positive associations between physical activity and cognitive test
      performance in depressed subjects have been proposed in clinical studies. The
      contribution of severity and recency of depressive symptoms at the population
      level is not known. AIMS: This study aims to examine whether regular physical
      activity associates with better verbal fluency and psychomotor speed in depressed
      subjects using a large population-based sample. METHODS: Data was obtained from
      the population-based Finnish Health 2000 Study, gathered in 2000-2001. Depressive
      symptoms and depressive disorders were assessed by the Beck Depression Inventory
      (BDI) and the Composite International Diagnostic Interview (CIDI),
      correspondingly. Cognitive test performance was assessed by the animal naming
      test and psychomotor speed with a simple and multi-choice reaction time test.
      Physical activity (Gothenburg scale) was self-reported. Complete data were
      obtained from 3658 subjects aged 30-64 years. Socio-demographic factors, health
      behaviours and use of antidepressants and anxiolytics were used as covariates in
      the linear regression models. Adjusted means were calculated using the predictive
      margins method. RESULTS: Regular physical activity associated with better
      performance in reaction time tests and better verbal fluency among men with
      depressive symptoms or with a major depressive episode. Physical activity also
      associated with cognitive test performance among non-depressed men and women, but
      among them the differences between the physical activity groups were smaller.
      CONCLUSION: Regular physical activity may be a useful tool in supporting
      neurocognitive functioning among depressed subjects.

PMID- 23167537
TI  - Haemodynamic influences on kidney oxygenation: clinical implications of
      integrative physiology.
AB  - Renal blood flow, local tissue perfusion and blood oxygen content are the major
      determinants of oxygen delivery to kidney tissue. Arterial pressure and segmental
      vascular resistance influence kidney oxygen consumption through effects on
      glomerular filtration rate and sodium reabsorption. Diffusive shunting of oxygen
      from arteries to veins in the cortex and from descending to ascending vasa recta
      in the medulla limits oxygen delivery to renal tissue. Oxygen shunting depends on
      the vascular network, renal haemodynamics and kidney oxygen consumption.
      Consequently, the impact of changes in renal haemodynamics on tissue oxygenation
      cannot necessarily be predicted intuitively and, instead, requires the
      integrative approach offered by computational modelling and multiple measuring
      modalities. Tissue hypoxia is a hallmark of acute kidney injury (AKI) arising
      from multiple initiating insults, including ischaemia-reperfusion injury,
      radiocontrast administration, cardiopulmonary bypass surgery, shock and sepsis.
      Its pathophysiology is defined by inflammation and/or ischaemia resulting in
      alterations in renal tissue oxygenation, nitric oxide bioavailability and oxygen
      radical homeostasis. This sequence of events appears to cause renal
      microcirculatory dysfunction, which may then be exacerbated by the inappropriate
      use of therapies common in peri-operative medicine, such as fluid resuscitation.
      The development of new ways to prevent and treat AKI requires an integrative
      approach that considers not just the molecular mechanisms underlying failure of
      filtration and tissue damage, but also the contribution of haemodynamic factors
      that determine kidney oxygenation. The development of bedside monitors allowing
      continuous surveillance of renal haemodynamics, oxygenation and function should
      facilitate better prevention, detection and treatment of AKI.

PMID- 23167538
TI  - Treatment of steroid-resistant acute renal allograft rejection with alemtuzumab.
AB  - Steroid-resistant renal allograft rejections are commonly treated with rabbit
      antithymocyte globulin (RATG), but alemtuzumab could be an effective, safe and
      more convenient alternative. Adult patients with steroid-resistant renal
      allograft rejection treated with alemtuzumab (15-30 mg s.c. on 2 subsequent days)
      from 2008 to 2012 (n = 11) were compared to patients treated with RATG (2.5-4.0
      mg/kg bodyweight i.v. for 10-14 days; n = 20). We assessed treatment-failure
      (graft loss, lack of improvement of graft function or need for additional anti
      rejection treatment), infections during the first 3 months after treatment and
      infusion-related side effects. In both groups, the median time-interval between
      rejection and transplantation was 2 weeks, and approximately 75% of rejections
      were classified as Banff-IIA or higher. Three alemtuzumab-treated patients (27%)
      experienced treatment failure, compared to eight RATG treated patients (40%, p =
      0.70). There was no difference in the incidence of infections. There were mild
      infusion-related side-effects in three alemtuzumab-treated patients (27%), and
      more severe infusion-related side effects in 17 RATG-treated patients (85%, p =
      0.013). Drug related costs of alemtuzumab-treatment were lower than of RATG
      treatment (?1050 vs. ?2024; p < 0.01). Alemtuzumab might be an effective therapy
      for steroid-resistant renal allograft rejections. In contrast to RATG,
      alemtuzumab is nearly devoid of infusion-related side-effects. These data warrant
      a prospective trial.

PMID- 23167539
TI  - Dephosphorylation reactions of mono-, di-, and triesters of 2,4-dinitrophenyl
      phosphate with deferoxamine and benzohydroxamic acid.
AB  - This work presents a detailed kinetic and mechanistic study of biologically
      interesting dephosphorylation reactions involving the exceptionally reactive
      nucleophilic group, hydroxamate. We compare results for hydroxamate groups
      anchored on the simple molecular backbone of benzohydroxamate (BHA) and on the
      more complex structure of the widely used drug, deferoxamine (DFO). BHA shows
      extraordinary reactivity toward the triester diethyl 2,4-dinitrophenyl phosphate
      (DEDNPP) and the diester ethyl 2,4-dinitrophenyl phosphate (EDNPP) but reacts
      very slowly with the monoester 2,4-dinitrophenyl phosphate (DNPP). Nucleophilic
      attack on phosphorus is confirmed by the detection of the phosphorylated
      intermediates formed. These undergo Lossen-type rearrangements, resulting in the
      decomposition of the nucleophile. DFO, which is used therapeutically for the
      treatment of acute iron intoxication, carries three hydroxamate groups and shows
      correspondingly high nucleophilic activity toward both triester DEDNPP and
      diester EDNPP. This result suggests a potential use for DFO in cases of acute
      poisoning with phosphorus pesticides.

PMID- 23167540
TI  - Diagnosis of silicotuberculosis by Endobronchial Ultrasound-Guided Transbronchial
      Needle Aspiration (EBUS-TBNA).

PMID- 23167541
TI  - Laser-assisted depigmentation for resistant vitiligo: a retrospective case series
      with long-term follow-up.
AB  - BACKGROUND: Blanching creams are used to depigment and to achieve uniform skin
      tone in widespread vitiligo. Length of the treatment and side-effects strongly
      limit their use in common practice. OBJECTIVES: To assess the long-term efficacy
      and tolerance of Q-Switched (QS) lasers for depigmenting the remaining unaffected
      skin in vitiligo. METHODS: Retrospective study of vitiligo patients treated with
      QS lasers in the Department of Dermatology of the University Hospital of Nice,
      France, from 2002 to 2011. Localizations and the percentage of body surface area
      of treated lesions, the total number of sessions and the possible relapses and
      side-effects, were analysed. Global satisfaction of the patients was evaluated on
      a visual analogical scale. RESULTS: Sixteen areas of normally pigmented skin were
      treated in six patients. The median number of sessions to achieve a complete
      depigmentation was 2 (1-6). The mean duration of follow-up was 36 months (19
      120). One third of the patients had no relapse. A complete repigmentation was
      observed after 21 months in one patient; a 50% repigmentation was noted in one
      patient, 7 months after the end of the treatment. Two patients showed a minimal
      repigmentation (<25%), 18 months and 9 years after the first laser treatments.
      The repigmentations were effectively treated with a maintenance session. The mean
      total number of sessions performed during this period was 3 (1-20). Side-effects
      were limited to transient purpura and crusts. The satisfaction of the patients
      was excellent (mean 9/10). conclusions: QS lasers appear as an efficient and safe
      modality for depigmenting normal skin in vitiligo.

PMID- 23167542
TI  - Unexpected effects of macromolecular crowding on protein stability.
AB  - Most theories about macromolecular crowding focus on two ideas: the
      macromolecular nature of the crowder and entropy. For proteins, the volume
      excluded by the crowder favors compact native states over expanded denatured
      states, enhancing protein stability by decreasing the entropy of unfolding. We
      tested these ideas with the widely used crowding agent Ficoll-70 and its monomer,
      sucrose. Contrary to expectations, Ficoll and sucrose have approximately the same
      stabilizing effect on chymotrypsin inhibitor 2. Furthermore, the stabilization is
      driven by enthalpy, not entropy. These results point to the need for carefully
      controlled studies and more sophisticated theories for understanding crowding
      effects.

PMID- 23167543
TI  - Effects of the Campylobacter jejuni CJIE1 prophage homologs on adherence and
      invasion in culture, patient symptoms, and source of infection.
AB  - BACKGROUND: Prophages of enteric bacteria are frequently of key importance for
      the biology, virulence, or host adaptation of their host. Some C. jejuni isolates
      carry homologs of the CJIE1 (CMLP 1) prophage that carry cargo genes potentially
      involved in virulence. Possible role(s) of CJIE1 homologs in the biology and
      virulence of C. jejuni were therefore investigated by using in vitro cell culture
      assays and by assessing the association of C. jejuni isolates with and without
      these prophages with patients' symptoms, with source, and with clonal lineages
      within the C. jejuni population. RESULTS: Four C. jejuni isolates, three carrying
      the CJIE1-like prophage and one without, were tested in cell culture assays for
      adherence and invasion. Both adherence and invasion of C. jejuni to cells in
      culture were increased by the presence of the CJIE1-family prophage. Differences
      in motility and growth rate did not appear to be responsible. The CJIE1 prophage
      was present in 23% of isolates from human and non-human sources combined that
      were obtained through sentinel-site surveillance, and the distribution of CJIE1
      in this population showed modest clonal associations. There was no correlation
      between the presence of the CJIE1 prophage in C. jejuni and patient symptoms,
      although there was some statistical support for lower rates of abdominal pain and
      fever when the prophage was present. Little evidence was found for a role of the
      prophage in host adaptation or host specificity. CONCLUSION: These biological
      effects suggest that the presence of the prophage may be a marker for
      differential virulence of some C. jejuni isolates. Ongoing research into the
      effects of the prophage on protein expression may provide additional insights
      into the roles the prophage may play in the biology of its host bacterium.

PMID- 23167544
TI  - Inactivation of Bacillus anthracis spores by single-walled carbon nanotubes
      coupled with oxidizing antimicrobial chemicals.
AB  - In this study, we investigated the sporicidal effects of single-walled carbon
      nanotubes (SWCNTs) and SWCNTs combined with oxidizing antimicrobial chemicals,
      H2O2 and NaOCl, on B. anthracis spores. The results indicated that treatment with
      SWCNTs alone exhibited little sporicidal effect on B. anthracis spores, while
      treatment with H2O2 or NaOCl alone showed moderate sporicidal effect. The
      combination treatment with SWCNTs (100 MUg/mL) and H2O2 (1.5%) or NaOCl (0.25%)
      exhibited much stronger sporicidal effect on the spores, compared to treatment
      with H2O2 or NaOCl alone at the same concentrations, doubling the log reduction
      of viable spore number (~3.3 log vs ~1.6 log). Such enhanced sporicidal
      efficiency was due to the synergistic effect contributed by the two individual
      antimicrobial mechanisms of SWCNTs and the oxidizing antimicrobial chemicals. The
      ordered sequential treatment with SWCNTs and H2O2 or NaOCl revealed that SWCNTs
      played the key role in making the spores more permeable/susceptible to chemicals.
      This study demonstrated the potential of combination treatment with SWCNTs and
      oxidizing antimicrobial agents in developing highly effective sporicidal
      agents/methods.

PMID- 23167545
TI  - Specialized functions of the PP2A subfamily II catalytic subunits PP2A-C3 and
      PP2A-C4 in the distribution of auxin fluxes and development in Arabidopsis.
AB  - Protein phosphorylation is a key molecular switch used to transmit information in
      biological signalling networks. The output of these signalling circuits is
      governed by the counteracting activities of protein kinases and phosphatases that
      determine the direction of the switch. Whereas many kinases have been
      functionally characterized, it has been difficult to ascribe precise cellular
      roles to plant phosphatases, which are encoded by enlarged gene families that may
      provide a high degree of genetic redundancy. In this work we have analysed the
      role in planta of catalytic subunits of protein phosphatase 2A (PP2A), a family
      encoded by five genes in Arabidopsis. Our results indicate that the two members
      of subfamily II, PP2A-C3 and PP2A-C4, have redundant functions in controlling
      embryo patterning and root development, processes that depend on auxin fluxes.
      Moreover, polarity of the auxin efflux carrier PIN1 and auxin distribution,
      determined with the DR5(pro) :GFP proxy, are affected by mutations in PP2A-C3 and
      PP2A-C4. Previous characterization of mutants in putative PP2A regulatory
      subunits had established a link between this class of phosphatases and PIN
      dephosphorylation and subcellular distribution. Building on those findings, the
      results presented here suggest that PP2A-C3 and PP2A-C4 catalyse this reaction
      and contribute critically to the establishment of auxin gradients for proper
      plant development.

PMID- 23167546
TI  - Cell-specific multifunctional processing of heterogeneous cell systems in a
      single laser pulse treatment.
AB  - Current methods of cell processing for gene and cell therapies use several
      separate procedures for gene transfer and cell separation or elimination, because
      no current technology can offer simultaneous multifunctional processing of
      specific cell subsets in highly heterogeneous cell systems. Using the cell
      specific generation of plasmonic nanobubbles of different sizes around cell
      targeted gold nanoshells and nanospheres, we achieved simultaneous
      multifunctional cell-specific processing in a rapid single 70 ps laser pulse bulk
      treatment of heterogeneous cell suspension. This method supported the detection
      of cells, delivery of external molecular cargo to one type of cells and the
      concomitant destruction of another type of cells without damaging other cells in
      suspension, and real-time guidance of the above two cellular effects.

PMID- 23167547
TI  - ACR Appropriateness Criteria (r) spinal bone metastases.
AB  - Abstract   The spine is a common site of involvement in patients with bone
      metastases. Apart from pain, hypercalcemia, and pathologic fracture, progressive
      tumor can result in neurologic deterioration caused by spinal cord compression or
      cauda equina involvement. The treatment of spinal bone metastases depends on
      histology, site of disease, extent of epidural disease, extent of metastases
      elsewhere, and neurologic status. Treatment recommendations must weigh the risk
      benefit profile of external beam radiation therapy (EBRT) for the particular
      individual's circumstance, including neurologic status, performance status,
      extent of spinal disease, stability of the spine, extra-spinal disease status,
      and life expectancy. Patients with spinal instability should be evaluated for
      surgical intervention. Research studies are needed that evaluate the combination
      or sequencing of localized therapies with systemic therapies including
      chemotherapy, hormonal therapy (HT), osteoclast inhibitors (OI), and
      radiopharmaceuticals. The roles of stereotactic body radiation therapy (SBRT) in
      the management of spinal oligometastasis, radioresistant spinal metastasis, and
      previously irradiated but progressive spinal metastasis are emerging, but more
      research is needed to validate the findings from retrospective studies. The
      American College of Radiology Appropriateness Criteria are evidence-based
      guidelines for specific clinical conditions that are reviewed every 2 years by a
      multidisciplinary expert panel. The guideline development and review include an
      extensive analysis of current medical literature from peer-reviewed journals and
      the application of a well-established consensus methodology (modified Delphi) 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- 23167548
TI  - Left ventricular rotation and twist assessed by four-dimensional speckle tracking
      echocardiography in healthy subjects and pathological remodeling: a single center
      experience.
AB  - BACKGROUND: Left ventricular (LV) twist represents a main aspect of ejection. It
      is defined as the difference between the apical and basal rotation and can be
      assessed by speckle tracking echocardiography (STE). Twist may be underestimated
      when assessed by two-dimensional-echocardiography due to the difficulty of
      identifying the real apex. Aim of this study was to evaluate the LV twist by
      means of three-dimensional (3D)-STE and verify if the inclusion of the apex can
      modify the assessment of the global twist. METHODS: LV volume acquisition with a
      fully sampled matrix array transducer was performed in 30 healthy subjects and 79
      patients with cardiomyopathy secondary to different etiologies. Thirty-nine
      patients had a LV ejection fraction (EF) >=50% (Group A), 16 showed an EF between
      40 and 50% (Group B), and 24 patients had an EF <=40%(Group C). LV rotation was
      assessed by 3D-STE at basal, medium, apical, and apical-cap levels. Twist was
      computed considering the apex either at the apical level (Twist(Api) ) or at the
      apical-cap level (Twist(AC) ). RESULTS: LV rotation resulted to be progressively
      higher from base to apical-cap (P < 0.0001) with a significant difference between
      the apex and the apical-cap level (6.20 +/- 3.90 degrees  vs. 10.23 +/- 7.52
      degrees ; P < 0.001). Such a difference was constantly found in all Groups (P <
      0.01 for Group A, P < 0.05 for Group B and C). Twist(Api) was also significantly
      lower than Twist(AC) both in the overall population (6.2 +/- 3.89 degrees  vs.
      10.23 +/- 7.51 degrees ; P < 0.001) and in the different subgroups ( CONTROLS:
      9.61 +/- 3.39 degrees  vs. 13.75 +/- 6.51 degrees ; Group A: 10.49 +/- 4.77
      degrees  vs. 16.37 +/- 8.49 degrees ; Group B: 6.67 +/- 3.44 degrees  vs. 9.14 +/
      5.55 degrees ; Group C: 33 +/- 2.62 degrees  vs. 5.26 +/- 3.74 degrees ; P <
      0.05 for all the comparisons). CONCLUSIONS: Identification and inclusion of
      apical-cap is relevant for twist assessment and can be carried out efficiently by
      3D-STE. The inclusion of the true apex in the calculation significantly affects
      the analysis of twist both in normal individuals and patients with different
      myocardial diseases.

PMID- 23167549
TI  - A case report describing a suspected rivaroxaban hypersensitivity reaction in a
      surgical patient.
AB  - WHAT IS KNOWN AND OBJECTIVE: Rivaroxaban is an oral anticoagulant, currently
      licensed for use as a venous thromboembolism (VTE) prophylaxis, and recommended
      by the National Institute for Clinical Excellence (NICE) for all patients
      undergoing elective hip and knee replacement surgery in the UK. We present the
      first case of a suspected hypersensitivity to rivaroxaban. CASE SUMMARY: A 57
      year-old man with no previous allergies underwent an uncomplicated, elective
      partial knee replacement, after which he was prescribed a routine 2-week course
      of rivaroxaban 10 mg. He developed an allergic response requiring readmission for
      assessment and treatment 7 days post-operatively. WHAT IS NEW AND CONCLUSION: We
      believe this to be the first published case of hypersensitivity associated with
      rivaroxaban. More research is needed to determine this association. At the same
      time, given the growing range and increasing use of anticoagulants, particular
      vigilance is required regarding potential side effects so that these may be
      managed quickly and effectively in the early stages.

PMID- 23167550
TI  - PaO2 oscillations caused by cyclic alveolar recruitment can be monitored in pig
      buccal mucosa microcirculation.
AB  - BACKGROUND: Cyclic alveolar recruitment and derecruitment play a role in the
      pathomechanism of acute lung injury and may lead to arterial partial pressure of
      oxygen (PaO(2) ) oscillations within the respiratory cycle. It remains unknown,
      however, if these PaO(2)  oscillations are transmitted to the microcirculation.
      The present study investigates if PaO(2)  oscillations can be detected in the pig
      buccal mucosa microcirculation. METHODS: Respiratory failure was induced by
      surfactant depletion in seven pigs. PaO(2)  oscillations caused by cyclic
      recruitment and derecruitment were measured in the thoracic aorta by fast
      fluorescence quenching of oxygen technology. Haemoglobin oxygen saturation,
      haemoglobin amount and blood flow in the buccal mucosa microcirculation were
      determined by combined fast white light spectrometry and laser Doppler flowmetry
      additionally to systolic arterial pressure. Measurements were performed during
      baseline conditions and during cyclic recruitment and derecruitment. RESULTS:
      Measurements remained stable during baseline. Respiratory-dependent oscillations
      occurred in the systemic circulation [PaO(2)  oscillations 92 (69-172) mmHg;
      systolic arterial pressure oscillations 33 (13-35) %] and were related to the
      respiratory rate (5.0 +/- 0.2/min) as confirmed by Fourier analysis. Synchronised
      oscillations were detected to the pig buccal mucosa microcirculation [haemoglobin
      oxygen saturation oscillations 3.4 (2.7-4.9) %; haemoglobin amount oscillations
      8.5 (2.3-13.3) %; blood flow oscillations 66 (18-87) %]. The delay between PaO(2)
      -? and microcirculatory oxygen oscillations was 7.2 +/- 2.8 s. CONCLUSION: The
      present study suggests that PaO(2)  oscillations caused by cyclic recruitment and
      derecruitment were transmitted to the buccal mucosa microcirculation. This non
      invasive approach of measuring oxygen waves as a surrogate parameter of cyclic
      recruitment and derecruitment could be used to monitor PaO(2)  oscillations at
      the bedside.

PMID- 23167551
TI  - Intrapartum nurses' perceived influence on delivery mode decisions and outcomes.
AB  - OBJECTIVE: To examine the role of the labor and delivery nurse in a nurse-managed
      practice model and nurses' perceived ability to influence decisions about mode of
      delivery and outcomes. DESIGN: Cross-sectional, descriptive, qualitative study.
      SETTING: One nurse-managed labor and delivery unit in a community-based hospital
      near a major metropolitan area. PARTICIPANTS: A purposeful sample of 13
      registered nurses with intrapartum experience. METHODS: Qualitative, in-depth
      interview data were subjected to content analysis. RESULTS: Experienced labor and
      delivery nurses perceived their role to be influential in decisions about mode of
      delivery. Negotiating for more time was integral to the way nurses exerted their
      influence, allowing for the time needed to implement practices that promote
      vaginal delivery. Knowledge of labor and physician practice patterns shaped the
      specific communication strategies used by nurses in their roles as negotiators.
      CONCLUSIONS: The responses of experienced, intrapartum nurses to actual and
      perceived time pressures and the subsequent impact on nurse-physician
      communication patterns and delivery mode outcomes are significant. Findings
      indicate the need to further explore how individual nursing practice may function
      as an independent predictor of delivery mode and how shared decision making among
      physicians, laboring women, and nurses affects rates of cesarean delivery.

PMID- 23167552
TI  - Web-based information for pregnant women and new mothers with type 1 diabetes--a
      description of the development process.
AB  - BACKGROUND: This paper describes the process of developing specifically designed
      web-based maternity information for women with type 1 diabetes. METHODS: A
      participatory design was used and the information was evaluated in seven stages
      by researchers, professional experts and users. All steps of the development
      process were noted in an online logbook. RESULTS: The information developed
      gradually and its contents were reviewed by nurse-midwives, nurses and physicians
      specializing in different key areas including diabetes care, paediatrics,
      obstetrics and breastfeeding, a clinical dietician and mothers with type 1
      diabetes. The draft was reviewed in regard to its cultural suitability and the
      information material was adjusted to meet quality criterions. Finally, the text
      was adapted for a lay audience. CONCLUSIONS: Using participatory design required
      time and resources, however; it proved a functional way of producing appropriate
      information for the target group.

PMID- 23167553
TI  - Endoscopic papillary large-balloon dilation following limited sphincterotomy for
      the removal of refractory bile duct stones: experience of 169 cases in a single
      Chinese center.
AB  - OBJECTIVE: To evaluate the efficacy and safety of endoscopic papillary large
      balloon dilation (EPLBD) combined with limited endoscopic sphincterotomy (EST)
      for the removal of large biliary duct stones (>=10 mm). METHODS: Data of patients
      who underwent an attempted removal of large bile duct stones by limited EST
      followed by EPLBD (>=12 mm in diameter) from April 2006 to October 2011 in our
      center were reviewed. Clinical characteristics, endoscopic methods and outcomes
      of the patients were collected and analyzed. RESULTS: A total of 169 patients
      with a mean age of 69.3 years (range 19-97 years) underwent 171 procedures.
      Median stone size and balloon diameter was 15 mm and 13 mm, respectively.
      Complete stone removal in a single session was achieved in 163 procedures (95.3%)
      with mechanical lithotripsy (ML) used in 66 (38.6%). Patients with a larger stone
      size required more frequent use of ML with a comparable success rate (P < 0.01).
      There were no significant differences between patients with and without
      periampullary diverticula in stone clearance (97.3% vs 93.8%), ML requirement
      (36.5% vs 40.2%) and complications (2.7% vs 6.2%) (all P > 0.05). Seven patients
      had eight procedure-related complications including moderate or mild bleeding (n
      = 4), minor perforation (n = 1), mild pancreatitis (n = 2) and cholangitis (n =
      1). CONCLUSION: EPLBD following limited EST is an effective and safe approach for
      the removal of large biliary duct stones, especially for those refractory cases.

PMID- 23167554
TI  - Structural investigation of anti-Trypanosoma cruzi 2-iminothiazolidin-4-ones
      allows the identification of agents with efficacy in infected mice.
AB  - We modified the thiazolidinic ring at positions N3, C4, and C5, yielding
      compounds 6-24. Compounds with a phenyl at position N3, 15-19, 22-24, exhibited
      better inhibitory properties for cruzain and against the parasite than 2
      iminothiazolidin-4-one 5. We were able to identify one high-efficacy trypanocidal
      compound, 2-minothiazolidin-4-one 18, which inhibited the activity of cruzain and
      the proliferation of epimastigotes and was cidal for trypomastigotes but was not
      toxic for splenocytes. Having located some of the structural determinants of the
      trypanocidal properties, we subsequently wished to determine if the exchange of
      the thiazolidine for a thiazole ring leaves the functional properties unaffected.
      We therefore tested thiazoles 26-45 and observed that they did not inhibit
      cruzain, but they exhibited trypanocidal effects. Parasite development was
      severely impaired when treated with 18, thus reinforcing the notion that this
      class of heterocycles can lead to useful cidal agents for Chagas disease.

PMID- 23167557
TI  - Cutaneous tumor cell load correlates with survival in patients with Sezary
      syndrome.
AB  - BACKGROUND: Sezary syndrome (SS) is defined by the triad of erythroderma,
      generalized lymphadenopathy and more than 1 000 circulating Sezary cells/MUl in
      the peripheral blood. PATIENTS AND METHODS: We screened the cutaneous lymphoma
      registry of our department for SS patients to identify clinical features of SS
      besides the defining criteria and to correlate them with disease survival.
      RESULTS: 24 SS patients were analyzed retrospectively. The mean age was 65 years
      with 62 % male patients. The median follow-up time was 32.5 months with an
      estimated 5-year overall survival rate of 76 %. All patients complained about
      itching and presented with palmoplantar keratoderma. 62.5 % had nail involvement,
      21 % alopecia, 12.5 % ectropion, 4 % prurigo nodularis, 8 % localized and 8 %
      generalized skin tumors, including leonine facies. In addition, 33 % had
      infections and also 33 % had venous thromboembolism. We identified cutaneous
      tumor cell load as a significant prognostic marker for SS. None of the other
      parameters were associated with disease specific survival. CONCLUSIONS:
      Clinically SS is characterized by various presentations beyond erythroderma. The
      cutaneous tumor cell load in SS is strongly associated with outcome and survival.
      We demonstrate a high risk for venous thromboembolism in SS patients who might
      benefit from anti-coagulation therapies.

PMID- 23167559
TI  - Probucol prevents blood-brain barrier dysfunction in wild-type mice induced by
      saturated fat or cholesterol feeding.
AB  - Dysfunction of the blood-brain barrier (BBB) is an early pathological feature of
      vascular dementia and Alzheimer's disease (AD) and is triggered by inflammatory
      stimuli. Probucol is a lipid-lowering agent with potent anti-oxidant properties
      once commonly used for the treatment of cardiovascular disease. Probucol therapy
      was found to stabilize cognitive symptoms in elderly AD patients, whereas in
      amyloid transgenic mice probucol was shown to attenuate amyloidosis. However, the
      mechanisms underlying the effects of probucol have note been determined. In the
      present study we investigated whether probucol can prevent BBB disturbances
      induced by chronic ingestion of proinflammatory diets enriched with either 20%
      (w/w) saturated fats (SFA) or 1% (w/w) cholesterol. Mice were fed the diets for
      12 weeks before they were killed and BBB integrity was measured. Mice maintained
      on either the SFA- or cholesterol-supplemented diets were found to have a 30- and
      sevenfold greater likelihood of BBB dysfunction, respectively, as determined by
      the parenchymal extravasation of plasma-derived immunoglobulins and endogenous
      lipoprotein enrichment with beta-amyloid. In contrast, mice fed the SFA- or
      cholesterol-enriched diets that also contained 1% (w/w) probucol showed no
      evidence of BBB disturbance. The parenchymal expression of glial fibrillary
      acidic protein, a marker of cerebrovascular inflammation, was significantly
      greater in mice fed the SFA-enriched diet. Plasma lipid, beta-amyloid and
      apolipoprotein B levels were not increased by feeding of the SFA- or cholesterol
      enriched diets. However, mice fed the SFA- or cholesterol-enriched diets did
      exhibit increased plasma non-esterified fatty acid levels that were not reduced
      by probucol. The data suggest that probucol prevents disturbances of BBB induced
      by chronic ingestion of diets enriched in SFA or cholesterol by suppressing
      inflammatory pathways rather than by modulating plasma lipid homeostasis.

PMID- 23167560
TI  - Foscarnet in the management of cytomegalovirus infections in hematopoietic stem
      cell transplant patients.
AB  - Despite significant advances in the day-to-day management of patients receiving
      hematopoietic stem cell transplantations, including the introduction of new
      antiviral drugs, cytomegalovirus (CMV) infection continues to be a major cause of
      morbidity and mortality. The aim of this article is to undertake a literature
      based review of foscarnet in this therapeutic setting and to align current best
      published evidence with recent recommendations presented at the European
      Conference on Infections in Leukaemia. Ganciclovir remains the mainstay of CMV
      infection/disease antiviral management protocols. However, approximately a third
      of patients develop severe neutropenia and others become resistant to
      ganciclovir, and thus, a reasonably large proportion of patients are not able to
      receive and/or continue with this medication. Foscarnet is a suitable option as
      both pre-emptive therapy or for the treatment of active disease in these
      patients. Randomized trials have demonstrated that foscarnet is equally effective
      when compared with ganciclovir for pre-emptive treatment of CMV infections: the
      outcome was comparable with ganciclovir in terms of control of antigenemia and
      survival rates. There is a paucity of information for its use in the prophylaxis
      of CMV, although preliminary data show that it was effective in some patients at
      high risk of CMV reactivation. The main adverse events associated with foscarnet
      are renal impairment, serum electrolyte and hemoglobin disturbances, seizures and
      local genital irritation/ulceration. Foscarnet is a well-established antiviral
      option in immunocompromised patients, and it is usually administered as a second
      line option to ganciclovir. In patients receiving hematopoietic stem cell
      transplantation, it has proven efficacy when used pre-emptively to treat CMV
      reactivation, as an alternative to and also in combination with ganciclovir.

PMID- 23167558
TI  - Self-management: a systematic review of outcome measures adopted in self
      management interventions for stroke.
AB  - PURPOSE: To systematically review the psychometric properties of outcome measures
      used in stroke self-management interventions (SMIs) to (1) inform researchers,
      clinicians and commissioners about the properties of the measures in use and (2)
      make recommendations for the future development of self-management measurement in
      stroke. METHODS: Electronic databases, government websites, generic internet
      search engines and hand searches of reference lists. Abstracts were selected
      against inclusion criteria and retrieved for appraisal and systematically scored,
      using the COSMIN checklist. RESULTS: Thirteen studies of stroke self-management
      originating from six countries were identified. Forty-three different measures
      (mean 5.08/study, SD 2.19) were adopted to evaluate self-SMIs. No studies
      measured self-management as a discreet concept. Six (46%) studies included
      untested measures. Eleven (85%) studies included at least one measure without
      reported reliability and validity in stroke populations. CONCLUSIONS: The use of
      outcome measures which are related, indirect or proxy indicators of self
      management and that have questionable reliability and validity, contributes to an
      inability to sensitively evaluate the effectiveness of stroke self-SMIs. Further
      enquiry into how the concept of self-management in stroke operates, would help to
      clarify the nature and range of specific self-management activities to be
      targeted and aid the selection of existing appropriate measures or the
      development of new measures.

PMID- 23167561
TI  - Is intravenous iron sucrose the treatment of choice for pregnant anemic women?
AB  - Anemia during pregnancy remains an important public health problem in developing
      countries like India. Anemia is the direct cause of 12-15% of maternal deaths.
      Iron deficiency is the commonest cause for anemia in the Indian subcontinent.
      Several preventive and therapeutic approaches are in practice. The available
      routes of iron supplementation are oral and intravenous. In spite of oral iron
      being least invasive, cheap and safe, the ineffectiveness of oral iron due to
      dietary inhibitors and poor compliance are well known. Intravenous iron sucrose
      can be a promising therapy for moderate to severely anemic pregnant women and has
      been in practice for quite some time in private and public health practices. In
      this article, we report the current evidence on the safety and efficacy of
      intravenous iron sucrose in anemic pregnant women on hematological and clinical
      outcomes. Though the evidence on its efficacy in improving hemoglobin and serum
      ferritin is convincing, its effect on maternal and fetal outcomes are unclear.
      This is primarily due to lack of well-designed and larger studies powered to
      detect difference in clinical outcomes. Hence, there is a need to gather evidence
      from a well-designed large randomized clinical trial conducted in a developing
      country. The results of such a study would feed into the national policy and
      would form the basis to frame guidelines for management of anemia in developing
      countries.

PMID- 23167562
TI  - Delayed diagnosis of fibrinogen Aalpha-chain amyloidosis after dual heart-kidney
      transplantation.

PMID- 23167563
TI  - Flexible all-solid-state asymmetric supercapacitors based on free-standing carbon
      nanotube/graphene and Mn3O4 nanoparticle/graphene paper electrodes.
AB  - We report the design of all-solid-state asymmetric supercapacitors based on free
      standing carbon nanotube/graphene (CNTG) and Mn(3)O(4) nanoparticles/graphene
      (MG) paper electrodes with a polymer gel electrolyte of potassium
      polyacrylate/KCl. The composite paper electrodes with carbon nanotubes or
      Mn(3)O(4) nanoparticles uniformly intercalated between the graphene nanosheets
      exhibited excellent mechanical stability, greatly improved active surface areas,
      and enhanced ion transportation, in comparison with the pristine graphene paper.
      The combination of the two paper electrodes with the polymer gel electrolyte
      endowed our asymmetric supercapacitor of CNTG//MG an increased cell voltage of
      1.8 V, a stable cycling performance (capacitance retention of 86.0% after 10,000
      continuous charge/discharge cycles), more than 2-fold increase of energy density
      (32.7 Wh/kg) compared with the symmetric supercapacitors, and importantly a
      distinguished mechanical flexibility.

PMID- 23167565
TI  - Multiple roles of extracellular polymeric substances on resistance of biofilm and
      detached clusters.
AB  - In this study, multiple roles of biofilm EPS were assessed with respect to the
      resistance of biofilm and detached biofilm clusters to chlorine disinfection.
      Strains from an opportunistic pathogen, Pseudomonas aeruginosa (wild type, EPS-
      and EPS+) with altered extracellular polymeric substances (EPS) secretion
      capabilities were tested. The impact of biofilm EPS quantity on disinfection was
      evaluated by monitoring biofilm viability, biofilm structure, removal of
      dissolved organic matter (DOM), and viability of detached biofilm simultaneously
      during chlorine disinfection. The obtained results suggested that the presence of
      EPS increased biofilm and detached biofilm resistance to chlorine in both
      presence and absence of DOM. The quantity of EPS had an effect on biofilm
      structure and the structural characteristics were closely related to both overall
      biofilm viability and the spatial distribution of viable cells within the
      biofilm. Additionally, the increased amount of EPS influenced selective removal
      of DOM with polar functional groups. However the DOM removal did not have a
      significant impact on the viability of biofilm cells during chlorine
      disinfection. Meanwhile, the viability of detached biofilm clusters, particularly
      the EPS overproducing strain, was significantly increased in the presence of DOM.
      The combined results suggested that biofilm EPS played multiple roles toward
      influencing the resistance of both biofilm and detached biofilm to disinfectant.

PMID- 23167564
TI  - Distinct disulfide isomers of MU-conotoxins KIIIA and KIIIB block voltage-gated
      sodium channels.
AB  - In the preparation of synthetic conotoxins containing multiple disulfide bonds,
      oxidative folding can produce numerous permutations of disulfide bond
      connectivities. Establishing the native disulfide connectivities thus presents a
      significant challenge when the venom-derived peptide is not available, as is
      increasingly the case when conotoxins are identified from cDNA sequences. Here,
      we investigate the disulfide connectivity of MU-conotoxin KIIIA, which was
      predicted originally to have a [C1-C9,C2-C15,C4-C16] disulfide pattern based on
      homology with closely related MU-conotoxins. The two major isomers of synthetic
      MU-KIIIA formed during oxidative folding were purified and their disulfide
      connectivities mapped by direct mass spectrometric collision-induced dissociation
      fragmentation of the disulfide-bonded polypeptides. Our results show that the
      major oxidative folding product adopts a [C1-C15,C2-C9,C4-C16] disulfide
      connectivity, while the minor product adopts a [C1-C16,C2-C9,C4-C15]
      connectivity. Both of these peptides were potent blockers of Na(V)1.2 (K(d)
      values of 5 and 230 nM, respectively). The solution structure for MU-KIIIA based
      on nuclear magnetic resonance data was recalculated with the [C1-C15,C2-C9,C4
      C16] disulfide pattern; its structure was very similar to the MU-KIIIA structure
      calculated with the incorrect [C1-C9,C2-C15,C4-C16] disulfide pattern, with an
      alpha-helix spanning residues 7-12. In addition, the major folding isomers of MU
      KIIIB, an N-terminally extended isoform of MU-KIIIA identified from its cDNA
      sequence, were isolated. These folding products had the same disulfide
      connectivities as MU-KIIIA, and both blocked Na(V)1.2 (K(d) values of 470 and 26
      nM, respectively). Our results establish that the preferred disulfide pattern of
      synthetic MU-KIIIA and MU-KIIIB folded in vitro is 1-5/2-4/3-6 but that other
      disulfide isomers are also potent sodium channel blockers. These findings raise
      questions about the disulfide pattern(s) of MU-KIIIA in the venom of Conus
      kinoshitai; indeed, the presence of multiple disulfide isomers in the venom could
      provide a means of further expanding the snail's repertoire of active peptides.

PMID- 23167566
TI  - Telomere length and dynamics predict mortality in a wild longitudinal study.
AB  - Explaining variation in life expectancy between individuals of the same age is
      fundamental to our understanding of population ecology and life history
      evolution. Variation in the length and rate of loss of the protective telomere
      chromosome caps has been linked to cellular lifespan. Yet, the extent to which
      telomere length and dynamics predict organismal lifespan in nature is still
      contentious. Using longitudinal samples taken from a closed population of
      Acrocephalus sechellensis (Seychelles warblers) studied for over 20 years, we
      describe the first study into life-long adult telomere dynamics (1-17 years) and
      their relationship to mortality under natural conditions (n = 204 individuals).
      We show that telomeres shorten with increasing age and body mass, and that
      shorter telomeres and greater rates of telomere shortening predicted future
      mortality. Our results provide the first clear and unambiguous evidence of a
      relationship between telomere length and mortality in the wild, and substantiate
      the prediction that telomere length and shortening rate can act as an indicator
      of biological age further to chronological age when exploring life history
      questions in natural conditions.

PMID- 23167567
TI  - Biotic Abstract Dual Automata (BiADA): a novel tool for studying the evolution of
      porebiotic order (and the origin of life).
AB  - Biotic Abstract Dual Automata (BiADA), a novel simulation concept for studying
      the evolution of prebiotic order, has four main attributes. (1) The energy of
      each form of organization is the sum of two stocks: entropy-associated energy
      (E(s)) and free energy (E(g)), with dissimilar meaning, energy conductive, and
      energy exchange properties; (2) E(s) and E(g) have user-defined absolute values
      and are not derived from the relative thermodynamic parameters standard entropy
      and standard Gibbs free energy; (3) BiADA analyzes changes in both units of
      transformation and units of organization; and (4) BiADA-based models analyze
      forward and reverse transformations separately and the brut production of forms
      of organization. We discuss quantitative relationships between energy,
      information, and order parameters proposed in BiADA-based simulations. The
      example we show is that of a simple system with two forms of organization. The
      model monitors the energy flow and budget, the evolution of order and information
      capacity, and the energy cost of producing and maintaining the system's state. We
      show the effect of six prebiotic factors on the evolution of order and energy
      dissipative potential of the system. These are the initial state of the system,
      energy availability, the intrinsic energy conductivity, catalysis of "A to B"
      transformations, B autocatalysis, and the terminal heat sink. We discuss benefits
      of employing BiADA principles in the study of the origin of order in more complex
      networks.

PMID- 23167568
TI  - Oxidative status and histological changes in sea bass larvae muscle in response
      to high dietary content of docosahexaenoic acid DHA.
AB  - In previous studies, we observed dystrophic alterations in muscle of 48-day-old
      sea bass fed imbalanced docosahexaenoic acid (DHA) and vitamin E diets. To
      understand the whole pathological process associated with oxidative stress, a
      histological study was performed by feeding 14-day-old sea bass larvae with
      microdiets containing different ratios of DHA/vitamin E (1/150, 5/150 and 5/300)
      for a period of 21 days. Larvae fed diet 1/150 showed no lesions in contrast to
      larvae fed diets 5/150 and 5/300 where the highest incidence of muscle lesions
      and thiobarbituric acid reactive substances (TBARS) content was observed.
      Semithin sections revealed focal lesions consisting of degenerated fibres with
      hypercontracted myofilaments and extensive sarcoplasm vacuolization affecting
      both red and white muscle. Ultrathin sections of degenerating muscle fibres
      showed diffuse dilatation of sarcoplasmic reticulum, disorganized myofilaments
      and autophagic vacuoles containing myelin figures and dense bodies. Additionally,
      some macrophages were observed among injured fibres as numerous satellite cells.
      Results from the study agree with those obtained from previous work, proving the
      pathological potential of free radicals in sea bass larvae musculature. Moreover,
      high vitamin E inclusion could not completely protect cell membranes from free
      radicals action.

PMID- 23167569
TI  - Copper(II)- and palladium(II)-catalyzed enantioselective Claisen rearrangement of
      allyloxy- and propargyloxy-indoles to quaternary oxindoles and spirocyclic
      lactones.
AB  - In this Article, a strategy to obtain highly enantioselective catalysts for the
      Claisen rearrangement of allyloxy- and propargyloxy-indoles is outlined.
      Ultimately, copper BOX and palladium BINAP or PHOX catalysts were discovered as
      superior in catalyzing Claisen rearrangements of allyloxy- or proparyloxy
      substituted indoles to generate oxindoles bearing allyl- or allenyl-substituted
      quaternary centers. This method proved to be tolerant of a broad range of
      functional groups. Tandem reactions of the silyl-allene products provide rapid
      access to a variety of spirocyclic oxindoles in one operation.

PMID- 23167571
TI  - Functional assessment of donor and recipient left atrium in heart transplant
      patients using full-volume three-dimensional echocardiography.
AB  - BACKGROUND: Atrial function plays an important role in many cardiac conditions,
      how recipient and donor compartments of left atrium (LA) of transplanted hearts
      differentially contribute to overall LA function in transplanted hearts has not
      been described. We tested whether three-dimensional transthoracic
      echocardiography (3DE) could be used to calculate these compartment-specific
      atrial functions. METHODS AND RESULTS: We analyzed 3DE images of 22 consecutive
      transplant patients who had diagnostic imaging quality (ages 59 +/- 16 years)
      using TomTec Research Arena. The contour of the recipient and total LA were
      traced frame by frame, and the donor LA volume was calculated as the difference
      of the total LA volume minus the recipient LA volume. The LA ejection fractions
      of total LA, donor LA, and recipient LA were also calculated as (LA atrial end
      diastolic volume - LA atrial end-systolic volume)/LA atrial end-diastolic volume
      of each compartment. Interobserver variability of LA volumes for the total,
      recipient, and donor compartments were 5.6 +/- 2.4, 5.4 +/- 2.0, and 9.3 +/- 3.2
      mL, respectively (n = 11). The donor LA ejection fraction was higher than that of
      recipient (41 +/- 18% vs. 30 +/- 14%, P = 0.013). When the patients were
      categorized as asymptomatic (New York Heart Association functional class [NYHA]
      functional class I) and symptomatic (NYHA functional class II-III), indexed donor
      LA atrial end-diastolic volume was significantly lower in asymptomatic patients
      as compared with symptomatic patients. CONCLUSIONS: Compartment-specific LA
      volumes can be calculated in orthotopic heart transplant patients using full
      volume 3DE. Our findings may suggest that unique contribution of each LA
      compartment of transplanted hearts toward the symptoms of these patients.

PMID- 23167570
TI  - The plant short-chain dehydrogenase (SDR) superfamily: genome-wide inventory and
      diversification patterns.
AB  - BACKGROUND: Short-chain dehydrogenases/reductases (SDRs) form one of the largest
      and oldest NAD(P)(H) dependent oxidoreductase families. Despite a conserved
      'Rossmann-fold' structure, members of the SDR superfamily exhibit low sequence
      similarities, which constituted a bottleneck in terms of identification. Recent
      classification methods, relying on hidden-Markov models (HMMs), improved
      identification and enabled the construction of a nomenclature. However,
      functional annotations of plant SDRs remain scarce. RESULTS: Wide-scale analyses
      were performed on ten plant genomes. The combination of hidden Markov model (HMM)
      based analyses and similarity searches led to the construction of an exhaustive
      inventory of plant SDR. With 68 to 315 members found in each analysed genome, the
      inventory confirmed the over-representation of SDRs in plants compared to
      animals, fungi and prokaryotes. The plant SDRs were first classified into three
      major types - 'classical', 'extended' and 'divergent' - but a minority (10% of
      the predicted SDRs) could not be classified into these general types ('unknown'
      or 'atypical' types). In a second step, we could categorize the vast majority of
      land plant SDRs into a set of 49 families. Out of these 49 families, 35 appeared
      early during evolution since they are commonly found through all the Green
      Lineage. Yet, some SDR families - tropinone reductase-like proteins (SDR65C),
      'ABA2-like'-NAD dehydrogenase (SDR110C), 'salutaridine/menthone-reductase-like'
      proteins (SDR114C), 'dihydroflavonol 4-reductase'-like proteins (SDR108E) and
      'isoflavone-reductase-like' (SDR460A) proteins - have undergone significant
      functional diversification within vascular plants since they diverged from
      Bryophytes. Interestingly, these diversified families are either involved in the
      secondary metabolism routes (terpenoids, alkaloids, phenolics) or participate in
      developmental processes (hormone biosynthesis or catabolism, flower development),
      in opposition to SDR families involved in primary metabolism which are poorly
      diversified. CONCLUSION: The application of HMMs to plant genomes enabled us to
      identify 49 families that encompass all Angiosperms ('higher plants') SDRs, each
      family being sufficiently conserved to enable simpler analyses based only on
      overall sequence similarity. The multiplicity of SDRs in plant kingdom is mainly
      explained by the diversification of large families involved in different
      secondary metabolism pathways, suggesting that the chemical diversification that
      accompanied the emergence of vascular plants acted as a driving force for SDR
      evolution.

PMID- 23167572
TI  - Investigation of chiral inversion and pharmacokinetics of laevo-ornidazole by
      high-performance liquid chromatography.
AB  - WHAT IS KNOWN AND OBJECTIVE: Laevo-ornidazole is an enantiomer of ornidazole, a 5
      nitroimidazole antimicrobial agent. It is not known whether chiral inversion of
      laevo-ornidazole occurs in humans. The objective of this study was to investigate
      the possible chiral inversion and pharmacokinetics of the drug in vivo. METHODS:
      We developed a stereo-specific high-performance liquid chromatographic method for
      investigating chiral inversion of the drug and a standard high-performance liquid
      chromatography (HPLC) for the routine assay of the drug in pharmacokinetic
      studies. We report on the pharmacokinetics of the drug following single dose and
      multiple doses and investigate the effect of food in healthy volunteers. RESULTS
      AND DISCUSSION: There was no chiral inversion of laevo-ornidazole in vivo. In the
      pharmacokinetic study of the drug in healthy Chinese volunteers, food intake
      affected the absorption rate of laevo-ornidazole but not the extent. WHAT IS NEW
      AND CONCLUSION: We present the first reported method for the chiral separation of
      ornidazole in human plasma. We demonstrate the absence of chiral inversion of
      laevo-ornidazole in vivo. Given the absence on in vivo chiral inversion, we also
      report and validate a simplified non-chiral method for the determination of laevo
      ornidazole. We show that although food can affect the absorption rate of laevo
      ornidazole, the extent was unaffected.

PMID- 23167573
TI  - Kinetics of surfactant desorption at an air-solution interface.
AB  - The kinetics of re-equilibration of the anionic surfactant sodium dodecylbenzene
      sulfonate at the air-solution interface have been studied using neutron
      reflectivity. The experimental arrangement incorporates a novel flow cell in
      which the subphase can be exchanged (diluted) using a laminar flow while the
      surface region remains unaltered. The rate of the re-equilibration is relatively
      slow and occurs over many tens of minutes, which is comparable with the dilution
      time scale of approximately 10-30 min. A detailed mathematical model, in which
      the rate of the desorption is determined by transport through a near-surface
      diffusion layer into a diluted bulk solution below, is developed and provides a
      good description of the time-dependent adsorption data. A key parameter of the
      model is the ratio of the depth of the diffusion layer, H(c), to the depth of the
      fluid, H(f), and we find that this is related to the reduced Peclet number, Pe*,
      for the system, via H(c)/H(f) = C/Pe*(1/2). Although from a highly idealized
      experimental arrangement, the results provide an important insight into the
      "rinse mechanism", which is applicable to a wide variety of domestic and
      industrial circumstances.

PMID- 23167574
TI  - Efficacy of warm showers on labor pain and birth experiences during the first
      labor stage.
AB  - OBJECTIVE: To determine the efficacy of warm showers on parturition pain and the
      birth experiences of women during the first stage of labor. DESIGN: Randomized
      controlled trial (RCT). SETTING/PARTICIPANTS: The study was conducted from July
      10, 2010 to January 12, 2011 in the maternity ward of a Taipei City regional
      teaching hospital, site of approximately 220 to 250 births per month. Ninety-two
      expectant mothers were recruited (recruitment rate: 70.8%) and allocated by block
      randomization into the two arms of the study. In total, 80 women completed the
      trial: 41 in the control group and 39 in the experimental group. METHODS:
      Participants in the experimental group received warm shower bath interventions.
      Each shower lasted 20 minutes. After a 5-minute full body or lower back shower,
      participants could spend 15 minutes directing shower water toward any body region
      that felt most comfortable. Facilities allowed participants to stand and sit as
      desired. Water was constantly monitored and maintained at a temperature of 37
      degrees C. Participants in the control group received standard childbirth care.
      RESULTS: Labor pain and the birth experience were assessed using the Visual
      Analogue Scale for Pain (VASP) and the Labour Agentry Scale, respectively. After
      adjusting for demographic and obstetric data, experimental-group women who
      participated in warm showers reported significantly lower VASP scores at 4-cm and
      7-cm cervical dilations, and higher birth experiences than the control group.
      CONCLUSION: Apart from the positive physical hygiene effects, warm showers are a
      cost-effective, convenient, easy-to-deploy, nonpharmacological approach to pain
      reduction. This intervention helps women in labor to participate fully in the
      birthing process, earn continuous caregiver support, feel cared for and
      comforted, and have a more positive overall experience.

PMID- 23167575
TI  - Designed glucopeptides mimetics of myelin protein epitopes as synthetic probes
      for the detection of autoantibodies, biomarkers of multiple sclerosis.
AB  - We previously reported that CSF114(Glc) detects diagnostic autoantibodies in
      multiple sclerosis sera. We report herein a bioinformatic analysis of myelin
      proteins and CSF114(Glc), which led to the identification of five sequences.
      These glucopeptides were synthesized and tested in enzymatic assays, showing a
      common minimal epitope. Starting from that, we designed an optimized sequence,
      SP077, showing a higher homology with both CSF114(Glc) and the five sequences
      selected using the bioinformatic approach. SP077 was synthesized and tested on 50
      multiple sclerosis patients' sera, and was able to detect higher antibody titers
      as compared to CSF114(Glc). Finally, the conformational properties of SP077 were
      studied by NMR spectroscopy and structure calculations. Thus, the immunological
      activity of SP077 in the recognition of specific autoantibodies in multiple
      sclerosis patients' sera may be ascribed to both the optimized design of its
      epitopic region and the superior surface interacting properties of its C-terminal
      region.

PMID- 23167576
TI  - Comparison of visual acuity charts identifying visual impairment among older
      people outside the eye clinic.
AB  - PURPOSE: Evaluate the construct validity and describe sensitivity, specificity
      and predictive value of two short charts of visual acuity (VA) and examine
      whether these can identify and detect signs of visual impairment among older
      people. METHOD: The study included 43 persons, >65 years, with age related eye
      disease, living in their own homes. An ophthalmologist assessed the individuals'
      VA at an eye clinic with the 5 m KM chart. A research assistant assessed
      individuals' VA by the 1 m KM chart and the Visual Acuity Screening Test in their
      home environment. RESULTS: All persons with a VA level of <0.5 were correctly
      identified by both instruments. The instruments have good positive and negative
      predictive values for the 1 m KM chart (73% and 100%) and for the Visual Acuity
      Screening Test (69% and 100%). The construct validity between the instruments was
      good, but the assessment at the eye clinic assessed the participants as having
      higher VA level. CONCLUSIONS: Both instruments have good construct validity,
      considering they were carried out in poorer lighting conditions and a good
      predictive value for screening out VA levels <0.5. The 1 m KM chart showed the
      best agreement with the 5 m KM chart.

PMID- 23167578
TI  - Drug induced QT prolongation: the measurement and assessment of the QT interval
      in clinical practice.
AB  - There has been an increasing focus on drug induced QT prolongation including
      research on drug development and QT prolongation, following the removal of drugs
      due to torsades de pointes (TdP). Although this has improved our understanding of
      drug-induced QT prolongation there has been much less research aimed at helping
      clinicians assess risk in individual patients with drug induced QT prolongation.
      This review will focus on assessment of drug-induced QT prolongation in clinical
      practice using a simple risk assessment approach. Accurate measurement of the QT
      interval is best done manually, and not using the measurement of standard ECG
      machines. Correction for heart rate (HR) using correction formulae such as
      Bazett's is often inaccurate. These formulae underestimate and overestimate the
      duration of cardiac repolarization at low and high heart rates, respectively.
      Numerous cut-offs have been suggested as an indicator of an abnormal QT, but are
      problematic in clinical practice. An alternative approach is the QT nomogram
      which is a plot of QT vs. HR. The nomogram has an 'at risk' line and QT-HR pairs
      above this line have been shown in a systematic study to be associated with TdP
      and the line is more sensitive and specific than Bazett's QTc of 440 ms or 500
      ms. Plotting the QT-HR pair for patients on drugs suspected or known to cause QT
      prolongation allows assessment of the QT interval based on normal population QT
      variability. This risk assessment then allows the safer commencement of drugs
      therapeutically or management of drug induced effects in overdose.

PMID- 23167579
TI  - The effect of pre-procedure anxiety on sedative requirements for sedation during
      colonoscopy.
AB  - This study investigated the effects of pre-procedural anxiety (assessed using the
      Beck Anxiety Inventory) on sedative requirements in 135 patients undergoing
      sedation for colonoscopy. Deep sedation was defined as loss of consciousness and
      no response to colonoscopy, and was achieved by target-controlled infusion of
      propofol. Patients' characteristics, baseline haemodynamic profiles, Beck Anxiety
      Inventory scores, effect-site propofol concentration at loss of consciousness and
      characteristics of recovery were recorded. No correlations were found between
      Beck Anxiety Inventory scores and effect-site propofol concentration at loss of
      consciousness or baseline haemodynamic profiles. There was no statistical
      difference in the characteristics of recovery among patients with different
      levels of anxiety. In conclusion, in patients receiving deep sedation for
      colonoscopies, the level of pre-procedural anxiety did not relate to the sedative
      requirement or post-procedural recovery characteristics.

PMID- 23167580
TI  - Ensuring optimal breastfeeding and improvements in complementary feeding to
      improve infant and young child nutrition in developing countries.

PMID- 23167581
TI  - Enhancing young child nutrition and development in developing countries.

PMID- 23167582
TI  - Field-testing of guidance on the appropriate labelling of processed complementary
      foods for infants and young children in South Africa.
AB  - There is a lack of formal guidance from international normative bodies on the
      appropriate marketing of processed complementary foods. Such guidance is
      necessary to protect and promote optimal infant and young child feeding
      practices. The aim of this study was to field-test, in South Africa, the interim
      guidance provided by the Maternal, Infant and Young Child Nutrition Working
      Group's Draft Guide for Marketing Complementary Foods as a potential tool for use
      by manufacturers and national governments for guiding the appropriate labelling
      (as a subset of appropriate marketing practices) of complementary foods. This
      guidance was used to develop a checklist of questions and criteria for each
      possible answer, which was tested using a comprehensive database of labels from
      products purchased in South Africa from June to August 2011. One hundred and
      sixty product labels of 35 manufacturers were analysed, none of which complied
      with all checklist criteria. Fifty-six (35%) labels did not provide an
      appropriate age of introduction while 37 (23%) used images of infants appearing
      younger than 6 months. Nineteen (12%) labels suggested a daily ration too large
      for a breastfed child, and 32 (20%) potentially promote the manufacturer's infant
      formula. Only 58 (36%) labels were easy to read. The majority (69% and 92%) of
      labels provided instructions for safe and appropriate preparation/use and
      storage, respectively. The Draft Guide for Marketing Complementary Foods was
      found to be a useful tool for guiding the appropriate labelling of complementary
      foods, although some changes and additions are recommended to improve
      understanding, ease of use and to minimise the subjective interpretation of the
      guidance.

PMID- 23167583
TI  - The focused ethnographic study 'assessing the behavioral and local market
      environment for improving the diets of infants and young children 6 to 23 months
      old' and its use in three countries.
AB  - The concept of a focused ethnographic study (FES) emerged as a new methodology to
      answer specific sets of questions that are required by agencies, policymakers,
      programme planners or by project implementation teams in order to make decisions
      about future actions with respect to social, public health or nutrition
      interventions, and for public-private partnership activities. This paper
      describes the FES on complementary feeding that was commissioned by the Global
      Alliance for Improved Nutrition and highlights findings from studies conducted in
      three very different country contexts (Ghana, South Africa and Afghanistan)
      burdened by high levels of malnutrition in older infants and young children
      (IYC). The findings are analysed from the perspective of decision-making for
      future interventions. In Ghana, a primary finding was that in urban areas the
      fortified, but not instant cereal, which was being proposed, would not be an
      appropriate intervention, given the complex balancing of time, costs and health
      concerns of caregivers. In both urban and rural South Africa, home fortification
      products such as micronutrient powders and small quantity, lipid-based nutrient
      supplements (LNS) are potentially feasible interventions, and would require
      thoughtful behaviour change communication programmes to support their adoption.
      Among the important results for future decision-making for interventions in
      Afghanistan are the findings that there is little cultural recognition of the
      concept of special foods for infants, and that within households food procurement
      for IYC are in the hands of men, whereas food preparation and feeding are women's
      responsibilities.

PMID- 23167584
TI  - Screening for anti-nutritional compounds in complementary foods and food aid
      products for infants and young children.
AB  - A range of compounds with negative nutritional impact - 'anti-nutrients' - are
      found in most plant foods. The contents of anti-nutrients in processed foods
      depend on the ingredients and processing. Anti-nutrients in complementary foods
      for children can have a negative impact on nutritional status. The aim of this
      study was to screen complementary foods from developing countries for the anti
      nutritional compounds, phytate, polyphenols, inhibitors of trypsin and
      chymotrypsin, and lectins. Commercial products based on whole grain cereals were
      included as a 'worst-case' scenario for anti-nutrient exposure in Europe.
      Contents of minerals (iron, zinc and calcium), in which absorption or utilisation
      is affected by anti-nutrients, were analysed. Thirty-six products representing
      foods used in food aid programmes, local blended foods, fortified instant
      porridges and 'baby foods' were analysed. The content of minerals indicated that
      the fortification of a number of products did not meet the declared levels of
      iron, zinc and calcium. The phytate content ranged from 68 to 1536 mg/100 g,
      confirming a persistent problem of high levels of phytate in processed cereal-
      and legume-based products. The phytate : Fe molar ratio exceeded the recommended
      level of <1.0 in 32 of the 36 products. The total polyphenols varied from 1.3 to
      9.3 mg gentisic acid equivalents g(-1) . Screening low-molecular weight soluble
      polyphenols may be more relevant in complementary foods than total polyphenolic
      compounds. Trypsin and chymotrypsin inhibitors and lectins were found in residual
      amounts in most products, indicating efficient degradation by heat processing.
      However, young infants and malnourished children may have reduced pancreatic
      function, and upper limits for residual trypsin inhibitors are needed.

PMID- 23167585
TI  - Modelling linoleic acid and alpha-linolenic acid requirements for infants and
      young children in developing countries.
AB  - Essential fatty acids (EFAs), linoleic acid (LA) and alpha-linolenic acid (ALA),
      play a critical role in the growth and development of infants and young children.
      However, national guidelines for recommended intakes of EFAs are lacking in most
      developing countries. The objective of this study was to convert international
      EFA recommendations based on % of daily energy intake to recommended daily
      amounts for children aged 6-23 months in developing countries. The Food and
      Agriculture Organization (FAO) reports adequate intakes (AIs) for ALA as 0.4-0.6%
      of energy intake for children 6-23 months of age and as 3.0-4.5% of energy intake
      for LA. In order to estimate energy intakes, FAO daily energy requirements based
      on body weight were used. The daily AI amounts for these EFAs were calculated
      using the median body weight of the World Health Organization (WHO) Growth
      Standard population and median body weights with varying levels of malnutrition.
      The AI for ALA is equivalent to 0.3-0.4, 0.3-0.5 and 0.4-0.6 g day(-1), and the
      AI for LA is equivalent to 2.1-3.1, 2.4-3.5 and 2.8-4.3 g day(-1) for children
      aged 6-8, 9-11 and 12-23 months, respectively. While the lower median body
      weights of children in developing countries and associated reduced energy intake
      recommendations give lower estimated EFA requirements, recommendations based on
      median body weights in the WHO Reference Growth Standard is suggested. The upper
      levels of these calculated AIs are lower than or equal to those in North America
      (ALA: 0.5 and 0.7 g day(-1); LA: 4.6 and 7 g day(-1) for children aged 6-12
      months and 1-3 years, respectively). The FAO AIs (g day(-1)) calculated here for
      ALA and LA can serve as a guideline for developing countries for setting national
      standards.

PMID- 23167586
TI  - Sustainability of market-based community distribution of Sprinkles in western
      Kenya.
AB  - To evaluate the sustainability of market-based community distribution of
      micronutrient powders (Sprinkles((r)), Hexagon Nutrition, Mumbai, India.) among
      pre-school children in Kenya, we conducted in August 2010 a follow-up survey, 18
      months after study-related marketing and household monitoring ended. We surveyed
      849 children aged 6-35 months randomly selected from 60 study villages.
      Nutritional biomarkers were measured by fingerstick; demographic characteristics,
      Sprinkles purchases and use were assessed through household questionnaires. We
      compared Sprinkles use, marketing efforts and biomarker levels with the data from
      surveys conducted in March 2007, March 2008 and March 2009. We used logistic
      regression to evaluate associations between marketing activities and Sprinkles
      use in the 2010 survey. At the 2010 follow-up, 21.9% of children used Sprinkles
      in the previous 7 days, compared with 64.9% in 2008 (P < 0.001). Average intake
      was 3.2 sachets week(-1) in 2008, 1.6 sachets week(-1) in 2009 and 1.1 sachets
      week(-1) in 2010 (P < 0.001). Factors associated with recent Sprinkles use in
      2010 included young age [6-23 months vs. 24-35 months, adjusted odds ratio (aOR)
      = 1.5, P = 0.02], lowest 2 quintiles of socio-economic status (aOR = 1.7, P =
      0.004), household attendance at trainings or launches (aOR = 2.8, P < 0.001) and
      ever receiving promotional items including free Sprinkles, calendars, cups and t
      shirts (aOR = 1.7, P = 0.04). In 2010, there was increased prevalence of anaemia
      and malaria (P < 0.001), but not iron deficiency (P = 0.44), compared with that
      in 2008. Sprinkles use in 2010 was associated with decreased iron deficiency (P =
      0.03). Sprinkles coverage reduced after stopping household monitoring and
      reducing marketing activities. Continued promotion and monitoring of Sprinkles
      usage may be important components to sustain the programme.

PMID- 23167587
TI  - The relation between age of attainment of motor milestones and future cognitive
      and motor development in Bangladeshi children.
AB  - There is a need for easily administered, low-cost measures to assess child
      development in large field studies. Many researchers evaluate the age of
      attainment of motor milestones, but there is little information on their
      validity. A large longitudinal study (MINIMat) was conducted in a poor rural area
      of Bangladesh and we assessed the age of attainment of motor milestones in a
      subsample of over 2000 children. We examined their association with scores on the
      Bayley psychomotor development index (PDI) and mental development index (MDI) at
      18 months and with scores on the Movement Assessment Battery for Children and
      with intelligence quotient (IQ) on the Wechsler Preschool and Primary Scale of
      Intelligence at 64 months. A field worker visited the children's homes monthly
      from 3 to 12 months of age and then at 15 months and examined the children.
      Mothers recorded the date of attainment of the milestones. Age of attainment of
      walking and standing alone was moderately correlated with the PDI and had
      significant but low associations with later motor development. They were as good
      as the PDI in predicting later motor development and could be used in field
      studies for that purpose. Milestone age of attainment had significant but low
      correlations with MDI and later IQ. Height for age at 15 months was related to
      milestones and later IQ and motor development and accounted for some of the
      association between milestones and IQ. Milestone age of attainment may not be
      sensitive enough to be used as an indicator of later IQ.

PMID- 23167588
TI  - Nutrition in pregnancy and early childhood and associations with obesity in
      developing countries.
AB  - Concerns about the increasing rates of obesity in developing countries have led
      many policy makers to question the impacts of maternal and early child nutrition
      on risk of later obesity. The purposes of the review are to summarise the studies
      on the associations between nutrition during pregnancy and infant feeding
      practices with later obesity from childhood through adulthood and to identify
      potential ways for preventing obesity in developing countries. As few studies
      were identified in developing countries, key studies in developed countries were
      included in the review. Poor prenatal dietary intakes of energy, protein and
      micronutrients were shown to be associated with increased risk of adult obesity
      in offspring. Female offspring seem to be more vulnerable than male offspring
      when their mothers receive insufficient energy during pregnancy. By influencing
      birthweight, optimal prenatal nutrition might reduce the risk of obesity in
      adults. While normal birthweights (2500-3999 g) were associated with higher body
      mass index (BMI) as adults, they generally were associated with higher fat-free
      mass and lower fat mass compared with low birthweights (<2500 g). Low birthweight
      was associated with higher risk of metabolic syndrome and central obesity in
      adults. Breastfeeding and timely introduction of complementary foods were shown
      to protect against obesity later in life in observational studies. High-protein
      intake during early childhood however was associated with higher body fat mass
      and obesity in adulthood. In developed countries, increased weight gain during
      the first 2 years of life was associated with a higher BMI in adulthood. However,
      recent studies in developing countries showed that higher BMI was more related to
      greater lean body mass than fat mass. It appears that increased length at 2 years
      of age was positively associated with height, weight and fat-free mass, and was
      only weakly associated with fat mass. The protective associations between
      breastfeeding and obesity may differ in developing countries compared to
      developed countries because many studies in developed countries used formula
      feeding as a control. Future research on the relationship between breastfeeding,
      timely introduction of complementary feeding or rapid weight gain and obesity are
      warranted in developing countries. The focus of interventions to reduce risk of
      obesity in later life in developing countries could include: improving maternal
      nutritional status during pregnancy to reduce low birthweight; enhancing
      breastfeeding (including durations of exclusive and total breastfeeding); timely
      introduction of high-quality complementary foods (containing micronutrients and
      essential fats) but not excessive in protein; further evidence is needed to
      understand the extent of weight gain and length gain during early childhood are
      related to body composition in later life.

PMID- 23167589
TI  - Contemporary perspectives on talent identification and development in soccer.

PMID- 23167590
TI  - Laparoscopic colposuspension to the Cooper's ligament after hysterectomy for
      uterovaginal prolapse.
AB  - AIM: The goal of this study was to evaluate the long-term outcomes of
      laparoscopic colposuspension to the Cooper's ligament after hysterectomy for
      uterovaginal prolapse. MATERIAL AND METHODS: We performed chart reviews of 43
      patients with uterovaginal prolapse who underwent laparoscopic colposuspension to
      the Cooper's ligament after hysterectomy at Daejeon St. Mary's Hospital, Catholic
      University of Korea from 2003 to 2009. These patients exhibited grade 3 (29
      patients) or grade 4 (14 patients) uterovaginal prolapse. RESULTS: The mean age
      was 63.2 years (range, 39-76). The mean follow-up period was 44.2 months (95% CI,
      36.8-51.5). Forty-three patients showed no sign or recurrence of prolapse.
      Postoperative complications were tolerable and curable. Urinary frequency (2
      patients, 4.7%), voiding difficulty (2 patients, 4.7%), nocturia (1 patient,
      2.3%) and vaginal spotting (1 patient, 2.3%) were reported. CONCLUSION:
      Laparoscopic colposuspension using Cooper's ligament after hysterectomy could be
      an effective surgical option for the treatment of uterovaginal prolapse.

PMID- 23167591
TI  - Accuracy of endoscopic ultrasound-guided fine needle aspiration cytology on the
      differentiation of malignant and benign pancreatic cystic lesions: a single
      center experience.
AB  - OBJECTIVES: The aim was to compare the use of endoscopic ultrasound-guided fine
      needle aspiration (EUS-FNA) in cytology and the biochemical analysis of cyst
      fluid, together with the size of the lesion in the differentiation between benign
      and malignant pancreatic cystic lesions. METHODS: Data of patients who underwent
      EUS-FNA for pancreatic cystic lesions in our center from January 2006 to October
      2010 were retrospectively analyzed. The diagnostic accuracy of EUS-FNA was
      determined. RESULTS: Of the 56 patients, 37 (66.1%) had evaluable cytology for
      diagnosis and sufficient cyst fluid was available for biochemical analysis in
      58.9% (33/56) of the patients. The sensitivity, specificity, positive predictive
      value and negative predictive value of EUS-FNA for detecting malignancy were 63%,
      100%, 100% and 85%, respectively. EUS-FNA was the most accurate diagnostic method
      for differentiating malignant and benign pancreatic cystic lesions (88%). Cyst
      fluid carcinoembryonic antigen (CEA) > 365 ng/mL had a sensitivity of 100% for
      the detection of malignant cystic lesions. CONCLUSIONS: Although the rate of
      insufficient cyst fluid aspiration is high, the combination of cytological
      evaluation and CEA analysis of cyst fluid obtained by EUS-FNA is accurate in
      differentiating malignant cystic lesions from benign ones. Safe techniques are
      essential to improve the yield of cyst fluid aspiration by EUS.

PMID- 23167592
TI  - IB-LBM simulation of the haemocyte dynamics in a stenotic capillary.
AB  - To study the behaviour of a haemocyte when crossing a stenotic capillary, the
      immersed boundary-lattice Boltzmann method was used to establish a quantitative
      analysis model. The haemocyte was assumed to be spherical and to have an elastic
      cell membrane, which can be driven by blood flow to adopt a highly deformable
      character. In the stenotic capillary, the spherical blood cell was stressed both
      by the flow and the wall dimension, and the cell shape was forced to be stretched
      to cross the stenosis. Our simulation investigated the haemocyte crossing process
      in detail. The velocity and pressure were anatomised to obtain information on how
      blood flows through a capillary and to estimate the degree of cell damage caused
      by excessive pressure. Quantitative velocity analysis results demonstrated that a
      large haemocyte crossing a small stenosis would have a noticeable effect on blood
      flow, while quantitative pressure distribution analysis results indicated that
      the crossing process would produce a special pressure distribution in the cell
      interior and to some extent a sudden change between the cell interior and the
      surrounding plasma. 

PMID- 23167593
TI  - Homozygous truncation of SIX6 causes complex microphthalmia in humans.

PMID- 23167595
TI  - Cumulative impact of chaperone-mediated folding on genome evolution.
AB  - Molecular chaperones support protein folding and unfolding along with assembly
      and translocation of protein complexes. Chaperones have been recognized as
      important mediators between an organismal genotype and phenotype as well as
      important maintainers of cellular fitness under environmental conditions that
      induce high mutational loads. Here we review recent studies revealing that the
      folding assistance supplied by chaperones is evident in genomic sequences
      implicating chaperone-mediated folding as an influential factor during protein
      evolution. Interaction of protein with chaperones ensures a proper folding and
      function, yet an adaptation to obligatory dependence on such assistance may be
      irreversible, representing an evolutionary trap. A correlation between the
      requirement for a chaperone and protein expression level indicates that the
      evolution of substrate-chaperone interaction is bounded by the required substrate
      abundance within the cell. Accumulating evidence suggests that the utility of
      chaperones is governed by a delicate balance between their help in mitigating the
      risks of protein misfolding and aggregate formation on one hand and the slower
      rate of protein maturation and the energetic cost of chaperone synthesis on the
      other.

PMID- 23167596
TI  - Reduced workfunction intermetallic seed layers allow growth of porous n-GaN and
      low resistivity, ohmic electron transport.
AB  - Porous GaN crystals have been successfully grown and electrically contacted
      simultaneously on Pt- and Au-coated silicon substrates as porous crystals and as
      porous layers. By the direct reaction of metallic Ga and NH(3) gas through
      chemical vapor deposition, intermetallic metal-Ga alloys form at the GaN-metal
      interface, allowing vapor-solid-solid seeding and subsequent growth of porous
      GaN. Current-voltage and capacitance-voltage measurements confirm that the
      intermetallic seed layers prevent interface oxidation and give a high-quality
      reduced workfunction contact that allows exceptionally low contact resistivities.
      Additionally, the simultaneous formation of a lower workfunction intermetallic
      permits ohmic electron transport to n-type GaN grown using high workfunction
      metals that best catalyze the formation of porous GaN layers and may be employed
      to seed and ohmically contact a range of III-N compounds and alloys for broadband
      absorption and emission.

PMID- 23167594
TI  - Critical role of activation induced cytidine deaminase in experimental autoimmune
      encephalomyelitis.
AB  - Multiple Sclerosis (MS) is a neurodegenerative autoimmune disorder caused by
      chronic inflammation and demyelination within the central nervous system (CNS).
      Clinical studies in MS patients have demonstrated efficacy with B cell targeted
      therapies such as anti-CD20. However, the exact role that B cells play in the
      disease process is unclear. Activation Induced cytidine deaminase (AID) is an
      essential enzyme for the processes of antibody affinity maturation and isotype
      switching. To evaluate the impact of affinity maturation and isotype switching,
      we have interrogated the effect of AID-deficiency in an animal model of MS. Here,
      we show that the severity of experimental autoimmune encephalomyelitis (EAE)
      induced by the extracellular domain of human myelin oligodendrocyte glycoprotein
      (MOG1-125) is significantly reduced in Aicda deficient mice, which, unlike wild
      type mice, lack serum IgG to myelin associated antigens. MOG specific T cell
      responses are comparable between wild-type and Aicda knockout mice suggesting an
      active role for antigen experienced B cells. Thus affinity maturation and/or
      class switching are critical processes in the pathogenesis of EAE.

PMID- 23167597
TI  - VEGF in tumor progression and targeted therapy.
AB  - Progression of solid tumors depends on vascularization and angiogenesis in a
      malignant tissue. Among a whole range of proangiogenic factors, a vascular
      endothelial growth factor A (VEGF-A) plays a key role. Blockade of VEGF may lead
      to regression of vascular network and inhibition of a tumor growth. In the
      present time, bevacizumab has been introduced into wide clinical practice in
      therapy of breast cancer, colorectal cancer and recurrent high-grade gliomas
      (HGGs). Coadministration of antiangiogenic therapy with irinotecan may increase
      probability of the response to the treatment and prolong progression-free
      survival rate (PFS). Moreover, bevacizumab is well tolerated and significantly
      improves patient's quality of life. However, in the case of brain tumors, the
      efficiency of such an approach is controversial. The antiangiogenic therapy can
      slightly delay tumor growth and does not lead to complete recovery. In addition,
      it contributes to enhanced tumor cell invasion into the normal brain. The
      mechanisms of resistance include activation of alternative proangiogenic
      signaling pathways, of an invasive population of tumor cells, metabolic change
      toward glycolysis and recruitment of myeloid bone marrow-derived cells to tumors.
      Obviously, that anti-VEGF therapy as monotherapy was not effective against HGGs.
      To enhance the antitumor treatment efficacy, it is necessary to develop a multi
      target strategy to inhibit critical processes in malignancy progression such as
      angiogenesis, invasion, autophagy, metastatic spread, recruitment of bone marrow
      derived endothelial cells and tumor stem-like cells. In addition, anti-VEGF
      antibodies have shown a promising result as a tumor-targeting vector for delivery
      therapeutic and diagnostic drugs in brain tumors.

PMID- 23167598
TI  - Transversal analysis of public policies on user fees exemptions in six West
      African countries.
AB  - BACKGROUND: While more and more West African countries are implementing public
      user fees exemption policies, there is still little knowledge available on this
      topic. The long time required for scientific production, combined with the needs
      of decision-makers, led to the creation in 2010 of a project to support
      implementers in aggregating knowledge on their experiences. This article presents
      a transversal analysis of user fees exemption policies implemented in Benin,
      Burkina Faso, Mali, Niger, Togo and Senegal. METHODS: This was a multiple case
      study with several embedded levels of analysis. The cases were public user fees
      exemption policies selected by the participants because of their instructive
      value. The data used in the countries were taken from documentary analysis,
      interviews and questionnaires. The transversal analysis was based on a framework
      for studying five implementation components and five actors' attitudes usually
      encountered in these policies. RESULTS: The analysis of the implementation
      components revealed: a majority of State financing; maintenance of centrally
      organized financing; a multiplicity of reimbursement methods; reimbursement
      delays and/or stock shortages; almost no implementation guides; a lack of support
      measures; communication plans that were rarely carried out, funded or renewed;
      health workers who were given general information but not details; poorly
      informed populations; almost no evaluation systems; ineffective and poorly funded
      coordination systems; low levels of community involvement; and incomplete
      referral-evacuation systems. With regard to actors' attitudes, the analysis
      revealed: objectives that were appreciated by everyone; dissatisfaction with the
      implementation; specific tensions between healthcare providers and patients;
      overall satisfaction among patients, but still some problems; the perception that
      while the financial barrier has been removed, other barriers persist;
      occasionally a reorganization of practices, service rationing due to lack of
      reimbursement, and some overcharging or shifting of resources. CONCLUSIONS: This
      transversal analysis confirms the need to assign a great deal of importance to
      the implementation of user fees exemption policies once these decisions have been
      taken. It also highlights some practices that suggest avenues of future research.

PMID- 23167599
TI  - Genome sequence of dwarf birch (Betula nana) and cross-species RAD markers.
AB  - New sequencing technologies allow development of genome-wide markers for any
      genus of ecological interest, including plant genera such as Betula (birch) that
      have previously proved difficult to study due to widespread polyploidy and
      hybridization. We present a de novo reference genome sequence assembly, from 66*
      short read coverage, of Betula nana (dwarf birch) - a diploid that is the
      keystone woody species of subarctic scrub communities but of conservation concern
      in Britain. We also present 100 bp PstI RAD markers for B. nana and closely
      related Betula tree species. Assembly of RAD markers in 15 individuals by
      alignment to the reference B. nana genome yielded 44-86k RAD loci per individual,
      whereas de novo RAD assembly yielded 64-121k loci per individual. Of the loci
      assembled by the de novo method, 3k homologous loci were found in all 15
      individuals studied, and 35k in 10 or more individuals. Matching of RAD loci to
      RAD locus catalogues from the B. nana individual used for the reference genome
      showed similar numbers of matches from both methods of RAD locus assembly but
      indicated that the de novo RAD assembly method may overassemble some paralogous
      loci. In 12 individuals hetero-specific to B. nana 37-47k RAD loci matched a
      catalogue of RAD loci from the B. nana individual used for the reference genome,
      whereas 44-60k RAD loci aligned to the B. nana reference genome itself. We
      present a preliminary study of allele sharing among species, demonstrating the
      utility of the data for introgression studies and for the identification of
      species-specific alleles.

PMID- 23167600
TI  - Sirolimus inhibits lymphangiogenesis in rat renal allografts, a novel mechanism
      to prevent chronic kidney allograft injury.
AB  - Lymphangiogenesis occurs in renal allografts and it may be involved in the
      maintenance of the alloreactive immune response and thus participate in the
      development of chronic kidney allograft injury. Sirolimus (SRL) has been shown to
      inhibit lymphangiogenesis. The aim of this study was to describe
      lymphangiogenesis and its regulation during the development of chronic kidney
      allograft injury and to investigate the effect of SRL on allograft
      lymphangiogenesis and chronic kidney allograft injury. A rat renal
      transplantation model was used. Allografts treated with cyclosporine A or with
      SRL were analyzed in various time points. Syngenic transplantations were used as
      controls. Kidney function was followed with serum creatinine. Histology was
      analyzed by Chronic Allograft Damage Index (CADI). Immunohistochemistry was used
      to detect lymphatic vessels, VEGF-C and VEGFR-3. In cyclosporine-treated
      allografts VEGF-C/VEGFR-3 pathway was strongly upregulated leading to extensive
      lymphangiogenesis 60 days after transplantation. Lymphangiogenesis correlated
      positively with the CADI score. Sirolimus efficiently inhibited
      lymphangiogenesis, improved graft function and attenuated the development of
      chronic kidney allograft injury when compared with cyclosporine. In conclusion,
      lymphangiogenesis is associated with chronic kidney allograft injury and SRL is a
      potent inhibitor of lymphangiogenesis in renal allografts. Inhibition of
      lymphatic proliferation could mediate the nephroprotective properties of SRL.

PMID- 23167601
TI  - Mapping the global flow of steel: from steelmaking to end-use goods.
AB  - Our society is addicted to steel. Global demand for steel has risen to 1.4
      billion tonnes a year and is set to at least double by 2050, while the steel
      industry generates nearly a 10th of the world's energy related CO2 emissions.
      Meeting our 2050 climate change targets would require a 75% reduction in CO2
      emissions for every tonne of steel produced and finding credible solutions is
      proving a challenge. The starting point for understanding the environmental
      impacts of steel production is to accurately map the global steel supply chain
      and identify the biggest steel flows where actions can be directed to deliver the
      largest impact. In this paper we present a map of global steel, which for the
      first time traces steel flows from steelmaking, through casting, forming, and
      rolling, to the fabrication of final goods. The diagram reveals the relative
      scale of steel flows and shows where efforts to improve energy and material
      efficiency should be focused.

PMID- 23167602
TI  - Trifluoromethylation of alkenes by visible light photoredox catalysis.
AB  - A method for trifluoromethylation of alkenes has been developed employing visible
      light photoredox catalysis with CF(3)I, Ru(Phen)(3)Cl(2), and DBU. This process
      works especially well for terminal alkenes to give alkenyl-CF(3) products with
      only E-stereochemistry. The mild reaction conditions enable the
      trifluoromethylation of a range of alkenes that bear various functional groups.

PMID- 23167603
TI  - Population pharmacokinetics of rifampicin in Mexican patients with tuberculosis.
AB  - WHAT IS KNOWN AND OBJECTIVE: Rifampicin (RIF) shows wide variability in its
      pharmacokinetics. The purpose of this study was to develop and validate a
      population pharmacokinetic model to characterize the inter- and intra-individual
      variability in pharmacokinetic parameters of RIF in Mexican patients. METHODS:
      Ninety-four patients receiving antituberculosis therapy participated in this
      prospective study. Plasma concentration-time data were described using a one
      compartment model with lag time, absorption and first-order elimination. The
      potential influence of demographic and clinical characteristics of the patients,
      and the pharmaceutical formulation (A, B, C and D) on the pharmacokinetics
      parameters, was evaluated by non-linear mixed-effect modelling (nonmem). Seventy
      seven additional patients participated in the validation of the model. RESULTS
      AND DISCUSSION: The final population pharmacokinetic model obtained was as
      follows: apparent clearance CL/F = 8.17 L/h (1.40 as high for males), apparent
      distribution volume V(d)/F = 50.1 L (1.29 as high for males), absorption rate
      constant K(aA) = 0.391/h, K(aB,C,D) = 2.70/h, relative bioavailability F(A) =
      0.468, F(B,C,D) = 1, lag time in the absorption phase T(lag) = 0.264 h. The final
      model improved the precision on the parameter estimates (CL/F, V(d) /F and K(a)
      by 31.9%, 16.7% and 92.9%, respectively). The residual variability was 27.3%.
      WHAT IS NEW AND CONCLUSION: Gender was associated with changes in CL/F and V(d)
      /F whereas the pharmaceutical formulation was associated with changes in F and
      altered the K(a) . The validation data set showed that the model could be used in
      clinical practice for Bayesian dose adjustment of RIF in TB patients.

PMID- 23167604
TI  - The role of substrate wettability in nanoparticle transfer from wrinkled
      elastomers: fundamentals and application toward hierarchical patterning.
AB  - We report on the role of surface wettability during the printing transfer of
      nanoparticles from wrinkled surfaces onto flat substrates. As we demonstrate,
      this parameter dominates the transfer process. This effect can further be
      utilized to transfer colloidal particles in a structured fashion, if the
      substrates are patterned in wettability. The resulting colloidal arrangements are
      highly regular over macroscopic surface areas and display distinct pattern
      features in both the micrometer and nanoscale regime. We study the obtained
      structures and discuss the potential of this approach for creating hierarchical
      particle assemblies of high complexity. Our findings not only contribute to a
      better understanding of technologically relevant colloidal assembly processes,
      but also open new avenues for the realization of novel materials consisting of
      nanoparticles. In this regard, the presented structuring method is especially
      interesting for the design of optically functional surface coatings.

PMID- 23167606
TI  - Regulation of expression of ABCB1 and LRP genes by mitogen-activated protein
      kinase/extracellular signal-regulated kinase pathway and its role in generation
      of side population cells in canine lymphoma cell lines.
AB  - The concept of the cancer stem cell (CSC) has been recognized as key for
      elucidation of the mechanisms that confer the multidrug resistance (MDR)
      phenotype to tumor cells, and the side population (SP) fraction has been shown to
      be enriched by cells with the CSC phenotype. The purpose of the present study was
      to identify the mechanism that induces a difference of phenotype between the SP
      and the remaining major population (MP) using two canine lymphoma cell lines.
      Expression levels of ABCB1 and LRP genes, which encode efflux pumps, were
      significantly higher in the SP than in the MP. Microarray analysis revealed up
      regulation of the expression of transforming growth factor-beta (TGF-beta) type
      II receptor in SP compared with MP, and the mitogen-activated protein
      kinase/extracellular signal-regulated kinase (MAPK/ERK) pathway was more up
      regulated in the SP than in the MP. Stimulation of the MAPK/ERK pathway
      significantly increased the mRNA expression of both ABCB1 and LRP genes. These
      results indicate increased expression of the efflux pumps through the MAPK/ERK
      pathway in SP cells.

PMID- 23167607
TI  - The clinical behavior of 124 leukemic ovarian tumors: clues for improving the
      poor prognosis.
AB  - The clinical behavior of acute leukemic tumors at each organ site must be
      recognized if relapse is to be prevented. The courses of 124 cases of leukemic
      ovarian tumors were analyzed with survival durations obtained from authors. Local
      expansive growth and invasion of contiguous organs similar to epithelial ovarian
      cancer was seen in both acute myeloid (AML) and lymphoid (ALL) leukemias.
      Overall, 56% survived 1 year. Tumors at other sites were clinically apparent on
      presentation in over half the cases without simultaneous marrow relapse, and next
      relapse was as common in extramedullary sites as in marrow. Leukemic ovarian
      tumors were generally resistant to chemotherapy, and lengthy survivals were seen
      most often after complete excision together with systemic therapy. This study
      documents similar behavior in AML and ALL tumors and that they are rarely
      isolated to a single ovary. It suggests that scanning could improve our ability
      to find and eradicate occult tumors which, because of chemoresistance, prevent
      the cure of leukemia for most patients who develop them.

PMID- 23167605
TI  - Stress profiling of longevity mutants identifies Afg3 as a mitochondrial
      determinant of cytoplasmic mRNA translation and aging.
AB  - Although environmental stress likely plays a significant role in promoting aging,
      the relationship remains poorly understood. To characterize this interaction in a
      more comprehensive manner, we examined the stress response profiles for 46 long
      lived yeast mutant strains across four different stress conditions (oxidative,
      ER, DNA damage, and thermal), grouping genes based on their associated stress
      response profiles. Unexpectedly, cells lacking the mitochondrial AAA protease
      gene AFG3 clustered strongly with long-lived strains lacking cytosolic ribosomal
      proteins of the large subunit. Similar to these ribosomal protein mutants,
      afg3Delta cells show reduced cytoplasmic mRNA translation, enhanced resistance to
      tunicamycin that is independent of the ER unfolded protein response, and Sir2
      independent but Gcn4-dependent lifespan extension. These data demonstrate an
      unexpected link between a mitochondrial protease, cytoplasmic mRNA translation,
      and aging.

PMID- 23167608
TI  - Exploring the genetic landscape in chronic lymphocytic leukemia using high
      resolution technologies.
AB  - Abstract During recent years, microarray-based technologies and next-generation
      sequencing (NGS) have been applied in chronic lymphocytic leukemia (CLL) in order
      to identify novel genomic aberrations that may contribute to the pathogenesis of
      the disease. Even though high-resolution microarray studies have confirmed the
      importance of the known recurrent aberrations, i.e. del(11q), trisomy 12,
      del(13q) and del(17p), and have more precisely delineated the genomic borders of
      these aberrations, only a few novel aberrations, found at a low frequency, have
      been detected with these techniques. In contrast to this, the application of NGS
      technology of the coding genome (exome sequencing) or the entire genome (whole
      genome sequencing) has unveiled a number of novel recurrent mutations in e.g. the
      NOTCH1, SF3B1 and BIRC3 genes. Importantly, mutations in these latter genes were
      reported to be associated with a particularly poor outcome, similar to TP53
      aberrations, and may play key roles in tumor development, treatment resistance
      and prognosis. In this review, we not only summarize the latest achievements
      using array-based or NGS technologies, but also point to new directions for
      research aiming to unravel the complex genetic "map" in CLL and its prognostic
      subsets. 

PMID- 23167609
TI  - Polymer microneedles for transdermal drug delivery.
AB  - A microneedle system has been developed to deliver chemical and biological agents
      through the stratum corneum, which is the main barrier to drug delivery.
      Recently, microneedles have been fabricated from various kinds of polymers,
      including biocompatible polymer, biodegradable polymer, and water-soluble
      polymer. Polymer microneedles offer the benefits of ease of fabrication, cost
      effectiveness, and mass production, as well as controlled drug release using the
      water solubility and degradation properties of polymer. In this review, the key
      features of polymer microneedles are discussed, including fabrication, materials,
      mechanical properties, drug delivery properties, and applications. Polymer
      microneedles provide a promising method for transdermal drug delivery by
      utilizing various physical and chemical properties of polymer.

PMID- 23167610
TI  - The effect of smoking on myocardial performance index in middle-aged males after
      first acute myocardial infarction.
AB  - BACKGROUND: Cigarette smoking is associated with increased rates of coronary
      artery disease and acute myocardial infarction (MI). Paradoxically, smokers had
      lower mortality after MI. The purpose of this study was to evaluate the effect of
      chronic smoking on myocardial performance index (MPI) in middle-aged men after an
      acute MI. MATERIAL AND METHODS: A total of 429 patients (325 smokers vs. 104
      nonsmokers) presenting with acute ST elevation MI were enrolled in this study.
      Thrombolysis in myocardial infarction (TIMI) flow of the infarct related artery
      was measured before and after the primary percutaneous coronary intervention
      (PCI), and Gensini score was also calculated. Conventional echocardiography and
      tissue Doppler echocardiography (TDI) were performed within 48-72 hours after
      onset of chest pain. Peak early (Em) and late (Am) diastolic velocities, peak
      systolic (Sm) mitral annular velocities and time intervals were recorded with
      TDI. The MPI, ratio of Em/Am, and E/Em were calculated. RESULTS: Baseline
      demographic and angiographic characteristics such as Gensini score, pre and, post
      PCI TIMI flow were similar in 2 groups. In contrast, LV MPI was preserved among
      smokers (0.59 +/- 0.15 vs. 0.66 +/- 0.14, P = 0.01), and Em/Am values were also
      higher in smokers (0.84 +/- 0.28 vs. 0.75 +/- 0.31, P = 0.01). Independent
      predictors of impaired MPI (>=0.60) were determined as nonsmoking status (odds
      ratio 2.940, 95% CI 0.98-5.83, P = 0.05), left anterior descending artery
      stenosis (odds ratio 3.196, 95% CI 1.73-5.91 P = 0.001), and, age (odds ratio
      1.12, 95% CI 1.03-1.22, P = 0.01). CONCLUSIONS: Despite similar demographic and
      angiographic characteristics, smoker males had a paradoxically better MPI after
      acute MI.

PMID- 23167611
TI  - Hospital staff education on severe sepsis/septic shock and hospital mortality: an
      original hypothesis.
AB  - BACKGROUND: Signs of serious clinical events overlap with those of sepsis. We
      hypothesised that any education on severe sepsis/septic shock may affect the
      outcome of all hospital patients. We designed this study to assess the trend of
      the mortality rate of adults admitted to hospital for at least one night in
      relationship with a hospital staff educational program dedicated to severe
      sepsis/septic shock. METHODS: This study was performed in six Italian hospitals
      in the same region. Multidisciplinary Sepsis Teams members were selected by each
      hospital management among senior staff. The education included the following
      steps: i) the Teams were taught about adult learning, problem based learning, and
      Surviving Sepsis guidelines, and provided with educational material (literature,
      electronic presentations, scenarios of clinical cases for training and booklets);
      ii) they started delivering courses and seminars each to their own hospital staff
      in the last quarter of 2007.To analyse mortality, we selected adult patients,
      admitted for at least one night to the wards or units present in all the study
      hospitals and responsible for 80% of hospital deaths. We fitted a Poisson model
      with monthly hospital mortality rates from December 2003 to August 2009 as
      dependent variable. The effect of the educational program on hospital mortality
      was measured as two dummy variables identifying a first (November 2007 to
      December 2008) and a second (January to August 2009) education period. The
      analysis was adjusted for a linear time trend, seasonality and monthly average
      values of age, Charlson score, length of stay in hospital and urgent/non-urgent
      admission. RESULTS: The hospital staff educated reached 30.6% at the end of June
      2009. In comparison with the pre-education period, the Relative Risk of death of
      the patient population considered was 0.93 (95% confidence interval [CI] 0.87
      0.99; p 0.025) for in-patients in the first, and 0.89 (95% CI 0.81-0.98; p 0.012)
      for those in the second period after education. CONCLUSION: Our hypothesis that a
      program educating hospital staff to early detection and treatment of severe
      sepsis/septic shock may affect the outcome of all hospital patients is original,
      but it has to be corroborated by other experiences.

PMID- 23167612
TI  - Antiviral activity of casein and alphas2 casein hydrolysates against the
      infectious haematopoietic necrosis virus, a rhabdovirus from salmonid fish.
AB  - Salmonid fish viruses, such as infectious haematopoietic necrosis virus (IHNV),
      are responsible for serious losses in the rainbow trout and salmon-farming
      industries, and they have been the subject of intense research in the field of
      aquaculture. Thus, the aim of this work is to study the antiviral effect of milk
      derived proteins as bovine caseins or casein-derived peptides at different stages
      during the course of IHNV infection. The results indicate that the 3-h fraction
      of casein and alpha(S2) -casein hydrolysates reduced the yield of infectious IHNV
      in a dose-dependent manner and impaired the production of IHNV-specific antigens.
      Hydrolysates of total casein and alpha(S2) -casein target the initial and later
      stages of viral infection, as demonstrated by the reduction in the infective
      titre observed throughout multiple stages and cycles. In vivo, more than 50%
      protection was observed in the casein-treated fish, and the kidney sections
      exhibited none of the histopathological characteristics of IHNV infection. The
      active fractions from casein were identified, as well as one of the individual
      IHNV-inhibiting peptides. Further studies will be required to determine which
      other peptides possess this activity. These findings provide a basis for future
      investigations on the efficacy of these compounds in treating other viral
      diseases in farmed fish and to elucidate the underlying molecular mechanisms of
      action. However, the present results provide convincing evidence in support of a
      role for several milk casein fractions as suitable candidates to prevent and
      treat some fish viral infections.

PMID- 23167613
TI  - Identification of the sex pheromone of the mealybug Dysmicoccus grassii Leonardi.
AB  - Studies about the sex pheromone of the mealybug  Dysmicoccus grassii , a main
      pest of Canary Islands banana cultivars, showed strong evidence that (-)-(R)
      lavandulyl propionate and acetate in a 6:1 ratio are principal components of it.
      Volatile collection and GC-MS analysis from aeration of virgin females allowed
      the structural elucidation of the compounds. The activity and stereochemistry of
      both substances were established by means of relative attraction of mealybug
      males to synthetic standards in competitive Petri dish bioassays. (R)-Lavandulyl
      propionate induced a stronger attractive effect when compared to (R)-lavandulyl
      acetate. The attractiveness of the mixture of the two compounds at the original
      source ratio showed no statistically significant difference from that of the sum
      of each of the single compounds alone, suggesting that both components are not
      synergistic but additive.

PMID- 23167614
TI  - Synthesis and biological evaluation of tylophorine-derived dibenzoquinolines as
      orally active agents: exploration of the role of tylophorine e ring on biological
      activity.
AB  - A series of novel tylophorine-derived dibenzoquinolines has been synthesized and
      their biological activity evaluated. Three assays were conducted: inhibition of
      cancer cell proliferation, inhibition of TGEV replication for anticoronavirus
      activity, and suppression of nitric oxide production in RAW264.7 cells (a measure
      of anti-inflammation). The most potent compound from these assays,
      dibenzoquinoline 33b, showed improved solubility compared to tylophorine 9a, in
      vivo efficacies in a lung A549 xenografted tumor mouse model and a murine paw
      edema model, good bioavailability, and no significant neurotoxicity (as tested by
      a rota-rod test for motor coordination). This is the first study to explore in
      detail the role of the tylophorine E ring on biological activity and very
      strongly suggests that tylophorine-derived dibenzoquinolines merit further
      development into orally active agents.

PMID- 23167615
TI  - Positive thyroid peroxidase antibody titer is associated with dysphoric moods
      during pregnancy and postpartum.
AB  - OBJECTIVE: To examine general dysphoric moods prospectively in women who tested
      positive for thyroid peroxidase autoantibodies (TPO) during pregnancy and
      postpartum. DESIGN: Longitudinal, correlational, two-group, observational study.
      SETTING: Perinatal clinics. PARTICIPANTS: Six-hundred thirty-one (631) pregnant
      women. METHODS: Participants were screened for TPO antibodies, and 63 were TPO
      euthyroid positive. All were asked to continue into a 6-month postpartum follow
      up and 47 agreed. A comparison group of TPO negative women (n = 72) was randomly
      selected for follow-up. Women were visited monthly for 6 months and a blood
      sample was obtained to measure thyroid stimulating hormone (TSH), a targeted
      physical exam was conducted, and a thyroid symptom checklist (Perceived Stress
      Scale) and the Profile of Mood States (POMS) checklist were completed. RESULTS:
      Pregnant TPO-positive women had significantly higher depressive symptoms and were
      more likely to score higher than 20 on the POMS depression (POMS-D) scale than
      TPO-negative women. The TPO-positive women had significantly higher depression,
      anger, and total mood disturbance scores postpartum than TPO-negative women,
      regardless of development of postpartum thyroiditis (n = 25). CONCLUSIONS: Our
      results suggest that the presence of TPO autoantibodies alone in euthyroid
      pregnant and postpartum women increases the possibility of negative dysphoric
      moods, especially depressive symptoms that cannot be explained by stress or
      demographic factors.

PMID- 23167616
TI  - How accurate is intraoperative frozen section in the diagnosis of ovarian tumors?
AB  - AIM: The aim of this study was to evaluate the accuracy of intraoperative frozen
      section of ovarian tumors and to analyze the factors that influence the accuracy.
      MATERIAL AND METHODS: We compared the frozen section diagnosis of 218 ovarian
      tumors with their final diagnosis in paraffin sections, over a period of 10 years
      from 1999 to 2008. RESULTS: Results were analyzed on two parameters: (i) status
      of malignancy and (ii) histological type. The overall accuracy was 95%. The
      sensitivity for benign, borderline and malignant tumors was 99.3%, 86.66% and
      96.3%, respectively. The corresponding specificities were 92.6%, 97% and 100%.
      Most of the discrepant cases were of borderline category. The overall accuracy
      for histological diagnosis was 80.7%. The number of sections examined at frozen
      and paraffin had a statistically significant association with the accuracy of
      frozen section. CONCLUSION: Frozen section diagnosis is of high quality at our
      center with a few exceptions in borderline category. The numbers of sections
      examined have a statistically significant influence on the accuracy of frozen
      section of ovarian masses.

PMID- 23167618
TI  - Computational framework to model and design surgical meshes for hernia repair.
AB  - Surgical procedures for hernia surgery are usually performed using prosthetic
      meshes. In spite of all the improvements in these biomaterials, the perfect match
      between the prosthesis and the implant site has not been achieved. Thus, new
      designs of surgical meshes are still being developed. Previous to implantation in
      humans, the validity of the meshes has to be addressed, and to date experimental
      studies have been the gold standard in testing and validating new implants.
      Nevertheless, these procedures involve long periods of time and are expensive.
      Thus, a computational framework for the simulation of prosthesis and surgical
      procedures may overcome some disadvantages of the experimental methods. The
      computational framework includes two computational models for designing and
      validating the behaviour of new meshes, respectively. Firstly, the beam model,
      which reproduces the exact geometry of the mesh, is set to design the weave and
      determine the stiffness of the surgical prosthesis. However, this implies a high
      computational cost whereas the membrane model, defined within the framework of
      the large deformation hyperelasticity, is a relatively inexpensive computational
      tool, which also enables a prosthesis to be included in more complex geometries
      such as human or animal bodies. 

PMID- 23167619
TI  - Experiences of carers supporting dying renal patients managed without dialysis.
AB  - AIM: To explore the impact of being a family carer to patients with stage 5
      chronic kidney disease managed without dialysis. BACKGROUND: Increasing numbers
      of patients with renal disease worldwide are making the decision not to embark on
      dialysis. This group has significant physical and psychological symptom burdens
      similar to or greater than those in advanced cancer patients. Little is known
      about the impact on family carers. DESIGN: Exploratory, qualitative design.
      METHODS: The study was undertaken with 19 carers caring for patients managed in a
      Renal Supportive Care Service in the UK between 2006-2008. Sixty-one semi
      structured interviews and detailed field notes inform the analysis. FINDINGS:
      'Caring from diagnosis to death' was the overarching theme illustrated by three
      sub-themes: (i) Caregiver's plight - making sense of the disease and potential
      deterioration; (ii) Having to care indefinitely; and (iii) Avoiding talk of
      death. 'Caring from diagnosis to death' coincides with an original concept
      analysis of renal supportive care, which is considered an adjunct to the
      management of patients with renal disease at all stages of their illness.
      CONCLUSION: There is a clear need for further research internationally and theory
      based nursing interventions to support carers of patients managed without
      dialysis. The development of a holistic, integrated care pathway based on carer
      perspectives, which includes identification of information needs related to
      original diagnosis, associated comorbidities, treatment options, prognosis, and
      assistance in developing strategies to manage communication with patients as the
      end of life approaches, is required.

PMID- 23167617
TI  - Building a brain in the gut: development of the enteric nervous system.
AB  - The enteric nervous system (ENS), the intrinsic innervation of the
      gastrointestinal tract, is an essential component of the gut neuromusculature and
      controls many aspects of gut function, including coordinated muscular
      peristalsis. The ENS is entirely derived from neural crest cells (NCC) which
      undergo a number of key processes, including extensive migration into and along
      the gut, proliferation, and differentiation into enteric neurons and glia, during
      embryogenesis and fetal life. These mechanisms are under the molecular control of
      numerous signaling pathways, transcription factors, neurotrophic factors and
      extracellular matrix components. Failure in these processes and consequent
      abnormal ENS development can result in so-called enteric neuropathies, arguably
      the best characterized of which is the congenital disorder Hirschsprung disease
      (HSCR), or aganglionic megacolon. This review focuses on the molecular and
      genetic factors regulating ENS development from NCC, the clinical genetics of
      HSCR and its associated syndromes, and recent advances aimed at improving our
      understanding and treatment of enteric neuropathies.

PMID- 23167620
TI  - Loss of lysophosphatidic acid receptor-3 suppresses cell migration activity of
      human sarcoma cells.
AB  - Lysophosphatidic acid (LPA) interacts with at least six G protein-coupled
      transmembrane LPA receptors (LPA(1)-LPA(6)). Recently, we have reported that
      LPA(3) indicated opposite effects on cell migration, depending on the cell types.
      In the present study, to assess an involvement of LPA(3) on cell migration of
      sarcoma cells, we generated LPA receptor-3 (LPAR3)-knockdown (HT1080-sh3 and HOS
      sh3, respectively) cells from fibrosarcoma HT1080 and osteosarcoma HOS cells, and
      measured their cell migration abilities. In cell motility assay with a Cell
      Culture Insert, both LPAR3-knockdown cells showed significantly lower cell motile
      activities than control cells. Next, to investigate the effect of LPAR3-knockdown
      on invasion activity, which degraded the extracellular matrices, the Matrigel
      coated filter was used. HT1080-sh3 cells showed significantly low invasive
      activity compared with control cells, while no invasive activity was found in HOS
      sh3 cells. In gelatin zymography, no significant difference of matrix
      metalloproteinase (MMP)-2 and MMP-9 activities were detected in all cells. The
      results indicated that LPA(3) acts as a positive regulator of cell motility and
      invasion in sarcoma cells, suggesting that LPA signaling pathway via LPA(3) may
      be involved in the progression of sarcoma cells.

PMID- 23167621
TI  - Insight into tissue unbound concentration: utility in drug discovery and
      development.
AB  - In a preclinical setting, plasma or whole tissue drug concentrations are often
      correlated with pharmacodynamics, although according to the free drug hypothesis,
      unbound drug concentration should be more pharmacologically relevant.
      Alternatively, blood concentrations may be a good surrogate for tissue
      concentration for passively permeable compounds. However, for a large number of
      compounds that are substrates for uptake and/or efflux transporters expressed at
      the tissue level, significant discrepancies are expected between unbound
      concentrations in blood and those in tissues. Consequently, attempts have been
      made to measure tissue unbound drug concentrations using tissue homogenates,
      slices and microdialysis. Mathematical expressions for calculating the rate and
      extent of drug distribution into tissues have also been established. For example,
      a ratio of unbound concentration in the tissue to that in plasma (K(p,uu)) is the
      best indicator of the extent of tissue distribution. Despite these technical
      advances, however, very few examples demonstrate a focus on tissue unbound drug
      concentrations in a preclinical setting. This review will illustrate various
      techniques to estimate tissue unbound drug concentrations, relevant parameters to
      calculate the rate and extent of tissue distribution and different factors
      affecting tissue unbound concentration. The review will also highlight various
      examples from the literature where tissue unbound drug concentrations have
      demonstrated a superior correlation with efficacy. The impact of tissue unbound
      drug concentrations on the projection of human efficacious dose is also
      discussed.

PMID- 23167623
TI  - Structural and rheological studies on growth of salt-free wormlike micelles
      formed by star-type trimeric surfactants.
AB  - We investigated the growth mechanisms of wormlike micelles formed by star-type
      trimeric surfactant (3C(12)trisQ) with a hydrocarbon chain length of 12 in an
      aqueous solution. A 3C(n)trisQ molecule consists of three hydrocarbon chains and
      three hydrophilic groups connected by spacer chains, where n is the carbon number
      in the hydrocarbon chain. Our recent studies showed that the aggregates formed by
      3C(12)trisQ exhibited sphere-to-rod transition and the growth of wormlike
      micelles in an aqueous solution in the absence of salt. We performed small-angle
      neutron scattering (SANS) and rheological measurements and investigated the
      aggregation behavior of 3C(12)trisQ with various surfactant volume fractions. All
      SANS profiles for the 3C(12)trisQ indicated peak-profiles in the q range of 0.02
      A(-1) < q < 0.05 A(-1), where the magnitude of the scattering vector q is defined
      by q = 4pi sin(theta/2)/lambda (lambda and theta represent the wavelength and
      scattering angle, respectively). These peaks were attributed to repulsive
      interparticle interactions between the micelles. The volume fraction dependence
      of the SANS peak-position was in agreement with the rheological behavior. These
      results suggest that 3C(12)trisQ shows sphere-to-rod transition and can produce
      wormlike micelles in the absence of salt. To determine the structural parameters
      quantitatively, model-fitting analysis was performed using a charged cylindrical
      or charged ellipsoidal particle scattering function. The radius, length, and
      number of water molecules per surfactant molecule (n(w)) inside the micelles were
      evaluated. The length increased and the n(w) value decreased with increasing phi,
      indicating that the growth of a wormlike micelle accompanies the extrusion of
      water from the micelle. The end-cap energies of star-type trimeric, gemini, and
      monomeric surfactants were evaluated from phi dependence of zero-shear viscosity.
      We found that wormlike micelles formed by 3C(12)trisQ exhibited a higher end-cap
      energy than gemini surfactant.

PMID- 23167622
TI  - Maternal mental health and infant dietary patterns in a statewide sample of
      Maryland WIC participants.
AB  - The study's objective was to examine the relation between maternal mental health
      and infant dietary intake. A cross-sectional, population-based telephone survey
      was employed within a statewide sample of Maryland Special Supplemental Nutrition
      Program for Women, Infants and Children participants. A 24-h diet recall was
      performed using the United States Department of Agriculture Automated Multiple
      Pass Method. Analyses presented were based on 689 mother-infant pairs. Overall,
      36.5% of mothers reported introducing solids to their infants early (<4 months of
      age), and 40% reported adding cereal to their infant's bottle. Among 0-6-month
      old infants, higher infant energy intake was associated with symptoms of maternal
      stress [beta=0.02; confidence interval (CI): 0.01, 0.04], depression (beta=0.04;
      CI: 0.01, 0.06) and overall maternal psychological distress (beta=0.02; CI:
      0.003, 0.03). With early introduction of solids in the model, the significant
      associations between infant energy intake and maternal stress and maternal
      psychological distress became marginal (P's=0.06-0.10). The association between
      infant energy intake and maternal depression remained significant (beta=0.03; CI:
      0.01, 0.06). Among 4-6-month-old infants, intakes of breads and cereals were
      higher among mothers who reported more symptoms of stress (beta=0.12; CI: 0.04,
      0.23), depression (beta=0.19; CI: 0.03, 0.34), anxiety (beta=0.15; CI: 0.02,
      0.27) and overall psychological distress (beta=0.04; CI: 0.01, 0.07). Among 7-12
      month-old infants, dietary intake was not related to mental health symptoms.
      Findings suggest poorer infant feeding practices and higher infant dietary intake
      during the first 6 months of age in the context of maternal mental health
      symptoms. Further research is needed to evaluate these effects on child dietary
      habits and growth patterns over time.

PMID- 23167624
TI  - Pteridine cleavage facilitates DNA photocleavage by Ru(II) polypyridyl compounds.
AB  - The synthesis, characterization, binding to calf thymus DNA, and plasmid DNA
      photocleavage studies of two ruthenium(II) pteridinylphenanthroline complexes are
      reported where the new pteridinylphenantholine ligands in these complexes are
      additions to a larger family designed to resemble DNA bases. [Ru(bpy)(2)(L
      keto)](PF(6))(2)1 is synthesized from ligand substitution of Ru(bpy)(2)Cl(2) by 4
      keto-pteridino[6,7-f]phenanthroline (L-keto). Increasing the reaction temperature
      during synthesis of 1 causes a ring scission of the L-keto ligand within the
      pyrimidine ring yielding a second Ru complex, [Ru(bpy)(2)(L-aap)](PF(6))(2)2
      where L-aap is 2-amino-3-amidopyrazino[5,6-f]phenanthroline. The ring cleavage
      reaction is accompanied by the loss of one carbon in the pyrimidine ring.
      Complexes 1 and 2 are characterized by (1)H NMR, UV/visible absorption and FT-IR
      spectroscopies and by cyclic voltammetry, and these results are presented in
      comparison to the previously reported related complexes [Ru(bpy)(2)(L
      allox)](PF(6))(2), [Ru(bpy)(2)(L-amino)](PF(6))(2), and
      [Ru(bpy)(2)(dppz)](PF(6))(2). In addition, 2 has been structurally characterized
      by X-ray diffraction. Both 1 and 2 are good intercalators of calf thymus DNA as
      determined by viscometry and binding constants obtained from absorption
      titrations. Only the ring-cleaved complex 2 exhibits a high degree of pBR322
      plasmid photocleavage in contrast to the other pteridinyl-phenanthroline
      complexes, which exhibit no plasmid DNA photocleavage. Complex 1, however,
      decomposes in buffer forming the photocleaver 2, demonstrating that sample age
      and reactivity can affect observed photocleavage. Complex 2 appears to
      photocleave DNA through a singlet oxygen mechanism.

PMID- 23167625
TI  - Selective COX-2 inhibitor (celecoxib) decreases cellular growth in prostate
      cancer cell lines independent of p53.
AB  - Celecoxib is a clinically available COX-2 inhibitor that has been reported to
      have antineoplastic activity. It has been proposed as a preventative agent for
      several types of early neoplastic lesions. Earlier studies have shown that
      sensitivity of prostatic carcinoma (PCa) to celecoxib is associated with
      apoptosis; however, these studies have not demonstrated adequately whether this
      effect is dependent on p53 status. We studied the relation between sensitivity to
      celecoxib and the phenotypic p53 status of PCa cells lines, LNCaP (wild type
      p53), PC3 (null p53) and DU145 (mutated p53). Cellular growth was assessed at 24,
      48, 72 and 96 h after celecoxib treatment at concentrations of 0, 10, 30, 50, 70
      and 100 MUM using an MTT assay. Cellular proliferation (Ki-67 expression) was
      determined by immunocytochemistry. Phenotypic expression of p53 was analyzed by
      western blotting. The effects of celecoxib on cellular growth and its association
      with p53 were assessed after down-regulation of p53 using synthetic interfering
      RNAs (siRNA) in LNCaP cells. Expression of p53 and COX-2 at mRNA levels was
      assessed by quantitative real time polymerase reaction (qRT-PCR). We found that
      celecoxib inhibited cellular growth and proliferation in a dose-dependent manner
      in all three cell lines; LNCaP cells with a native p53 were the most sensitive to
      celecoxib. We observed a down- regulation effect on p53 in LNCaP cells exposed to
      >= 30 MUM celecoxib for 72 h, but found no significant changes in the p53 levels
      of DU145 cells, which have a mutated p53. Reduced COX-2 expression was found with
      decreased p53 in LNCaP and PC-3 cells that were exposed to >= 20 MUM of celecoxib
      for 72 h, but COX-2 expression was increased in DU145 cells. All three cell lines
      demonstrated pan-cytotoxicity when exposed to 100 MUM celecoxib. When p53
      expression was inhibited using siRNA in LNCaP cells, the inhibitory effects on
      cellular growth usually exerted by celecoxib were not changed significantly.
      Celecoxib reduces the growth of prostate cancer cell lines in part by decreasing
      proliferation, which suggests that the inhibition of growth of LNCaP cells by
      celecoxib is independent of normal levels of native p53.

PMID- 23167626
TI  - Examination of caspase-dependent apoptotic and necrotic changes in rat kidney
      exposed to different doses of permethrin.
AB  - We investigated dose-related pathological alterations and apoptosis in rat kidney
      tissue exposed to permethrin. Histopathological findings, apoptotic cell death
      and urinary 3-phenoxybenzoic acid concentrations (3-PBA) were evaluated.
      Different doses of permethrin were administered to animals by oro-gastric gavage.
      A dose-dependent increase of urine 3-PBA concentration was observed in all the
      permethrin-treated groups. SDS-PAGE separated 30-45 kD and 100-220 kD protein
      bands in all experimental groups. Histopathologically, degenerative changes were
      observed in the epithelial lining of the S1, S2, and S3 segments of the renal
      proximal tubules. Apoptotic cells were seen in the inner stripe of the outer
      medulla in Group I, and both the cortex and medulla in Groups II and III.
      Immunohistochemical staining of caspase 3 and caspase 9 also was observed in the
      same areas. Our results suggest that damage to regions of the proximal tubules is
      dose-related, and caspase-9-dependent, mitochondria-related apoptotic cell death
      could play an important role in permethrin-induced nephrotoxicity. We also
      observed morphologically necrotic cells. We concluded that both necrosis and
      apoptosis are produced by permethrin.

PMID- 23167627
TI  - K and Au bicatalyst assisted growth of carbon nanocoils from acetylene: effect of
      deposition parameters on field emission properties.
AB  - We demonstrated the growth of carbon nanocoils (CNCs) via chemical vapor
      deposition (CVD) using Au and K metals as the catalysts to assist the thermal
      decomposition of C(2)H(2). Typical CNCs (wire diameter: 50-80 nm, coil diameter:
      110-140 nm, pitch: 100-200 nm, tens of micrometers), identified as amorphous
      coiled carbon fibers by scanning electron microscopy (SEM) and transmission
      electron microscopy (TEM), were grown at proper combinations of reaction
      parameters. Au nanoparticles (NPs), identified by energy dispersion X-ray
      spectroscopy (EDX) and electron diffraction (ED), were located at the tips of the
      CNCs. The observations suggested that a tip-growth mechanism involving the Au NPs
      as the nucleation sites was in operation. In the reaction, the liquid-phase K
      metal assisted the decomposition of C(2)H(2) by lowering the reaction
      temperature. We propose that acetylide and hydride intermediates were formed in
      the reaction. Further decomposition of the acetylide intermediates generated
      solid-phase carbon to grow the CNCs. Effects of varying the reaction conditions
      on the CNC growth were investigated. On the basis of the results, a Au and K
      bicatalyst enhanced tip-growth vapor-liquid-solid (VLS) mechanism was proposed to
      rationalize the CNC formation process. Electron field emission (EFE)
      characteristics of the CNCs were studied. The best EFE result showed a turn-on
      field (E(to)) of 3.78 V/MUm and a field enhancement factor (beta) of 1852. In
      addition, the current density (J) was as high as 43 mA/cm(2) at 6.87 V/MUm. The
      data suggest that the CNCs could be employed for field emission device
      applications.

PMID- 23167628
TI  - Macrocyclizations for medicinal chemistry: synthesis of druglike macrocycles by
      high-concentration Ullmann coupling.
AB  - Conditions have been identified for the efficient Ullmann macrocyclization of
      phenol and imidazole nucleophiles with aryl iodides at high reaction
      concentrations of up to 100 mM and using 5-10 mol % loading of an inexpensive
      copper catalyst. A range of substitution patterns and ring sizes are tolerated,
      and the method has been exemplified by the synthesis of a set of druglike
      macrocycles.

PMID- 23167629
TI  - Common genetic variants in the myeloperoxidase and paraoxonase genes and the
      related cancer risk: a review.
AB  - Modern approaches in health care are moving toward the model of "personalized
      medicine." Today, current research in molecular biology and medicine is focused
      on developing genomic markers with predictive, therapeutic, and prognostic
      significance. One of the most widespread and significant genomic markers is the
      single nucleotide polymorphism (SNP), which represents a variation in DNA
      sequence when a single nucleotide differs between members of a biological species
      or paired chromosomes in an individual. Antioxidant defense enzymes break down
      dangerous reactive compounds, called reactive oxygen species, and prevent DNA
      strand from carcinogen-specific mutations. It is well known that inherited
      variations in genes that encode antioxidant defense enzymes may modulate
      individual susceptibility to cancer. In our previous study we have determined the
      predictive significance of several SNPs of superoxide dismutase (SOD) and
      glutathione peroxidase gene families in the context of cancer risk. The present
      review includes a summary and discussion of the current findings evaluating the
      role of SNPs of the myeloperoxidase (MPO) and paraoxanase (PON) genes in cancer
      occurrence and development. We suggest that rs2333227 (MPO_ -463G/A) and rs854560
      polymorphisms have a great predictive significance; they could probably be
      utilized as cancer predictors in the future. Also, we recommend further in-depth
      research for rs11079344 (MPO), rs8178406 (MPO), rs2243828 (MPO), rs662 (PON1),
      rs705379 (PON1), and PON1_304A/G polymorphisms. These SNPs may become significant
      cancer-associated biomarkers.

PMID- 23167630
TI  - Environmental toxicants--induced epigenetic alterations and their reversers.
AB  - Epigenetics has been emphasized in the postgenome era to clarify obscure health
      risks of environmental toxicants including endocrine disrupting chemicals (EDCs).
      In addition, mixed exposure in real life can modify health consequences of the
      toxicants. Particularly, some nutritional and dietary materials modify individual
      susceptibility through changes in the epigenome. Therefore, we focused on some
      environmental toxicants that induce epigenetic alterations, and introduced
      chemopreventive materials to reverse the toxicants-induced epigenetic
      alterations. Methodologically, we used global and specific DNA methylation as
      epigenetic end points and searched epigenetic modulators in food. We reviewed
      various epigenetic end points induced by environmental toxicants including
      alcohol, asbestos, nanomaterials, benzene, EDCs, metals, and ionizing radiation.
      The epigenetic end points can be summarized into global hypomethylation and
      specific hypermethylation at diverse tumor suppress genes. Exposure timing, dose,
      sex, or organ specificity should be considered to use the epigenetic end points
      as biomarkers for exposure to the epimutagenic toxicants. Particularly, neonatal
      exposure to the epimutagens can influence their future adult health because of
      characteristics of the epimutagens, which disrupt epigenetic regulation in
      imprinting, organogenesis, development, etc. Considering interaction between
      epimutagenic toxicants and their reversers in food, we suggest that multiple
      exposures to them can alleviate or mask epigenetic toxicity in real life. Our
      present review provides useful information to find new end points of
      environmental toxicants and to prevention from environment-related diseases.

PMID- 23167631
TI  - Peroxisome proliferator-activated receptor agonists and bladder cancer: lessons
      from animal studies.
AB  - This article reviews available animal studies on the possible link between the
      use of peroxisome proliferator-activated receptor (PPAR) agonists and bladder
      cancer, with further discussion on the possible implications to humans.
      Carcinogenicity studies suggest that the PPARgamma agonist pioglitazone and dual
      PPARalpha/gamma agonists such as ragaglitazar, muraglitazar, and naveglitazar may
      increase the risk of bladder cancer in a dose-responsive pattern in rats. It is
      interesting that bladder cancer related to PPAR agonists shows remarkable species
      and sex-specificity and has a predilection to occur in the ventral dome of
      bladder in rodents. While male rats treated with pioglitazone or muraglitazar
      have a higher propensity to develop bladder cancer than female rats, mice of both
      sexes do not develop bladder cancer even when exposed to very high doses. Direct
      genotoxicity or cytotoxicity of PPAR agonists is unlikely to be the mode of
      action because most of the parent compounds or their metabolites of the PPAR
      agonists are neither mutagenic nor genotoxic, and they are rarely excreted in the
      urine; but a receptor-mediated PPAR effect cannot be excluded. Some suggest a
      "urolithiasis hypothesis" referring to the formation of urinary solids and
      calculi, which subsequently causes bladder necrosis, regenerative proliferation,
      hypertrophy, and cancer. However, whether these animal findings could have human
      relevance is not yet fully understood. Some argue that the urolithiasis-induced
      bladder cancer might be rat-specific and would probably not be applicable to
      humans. An effect of increased urinary growth factors induced by PPAR agonists
      has also been proposed, but this requires more investigations. Before fully
      clarified, a balance between the risks and benefits of the use of pioglitazone,
      an approved oral antidiabetic agent that has recently been linked to an increased
      but not yet confirmed risk of bladder cancer in humans, should be justified for
      individual use.

PMID- 23167633
TI  - No need for rescue medication (NNR) as an easily interpretable efficacy outcome
      measure in analgesic trials: validation in an individual-patient meta-analysis of
      dental pain placebo-controlled trials of naproxen.
AB  - WHAT IS KNOWN AND OBJECTIVE: In analgesic trials, pain relief is often assessed
      using a pain-relief score. We aimed to assess, through a meta-analysis, whether
      absence of need for rescue medication (NNR) is a reliable outcome measure in the
      evaluation of acute pain relief. METHODS: Individual-patient meta-analysis of
      placebo-controlled trials of single-dose naproxen sodium 220 or 440 mg in dental
      pain. Efficacy estimates were based on NNR and compared with the more commonly
      used 50% maximum total pain relief score (50% TOTPAR). The trials included were
      the full set of trials sponsored by one manufacturer. RESULTS AND DISCUSSION:
      Need for rescue medication and 50% TOTPAR gave comparable estimates of efficacy
      of naproxen sodium (220 and 440 mg) relative to placebo in dental pain at both 8
      and 12 h after dosing. WHAT IS NEW AND CONCLUSION: No need for rescue medication
      is a reliable outcome measure for use in acute pain trials. As it is more readily
      understandable than 50% TOTPAR, it should be the preferred primary outcome
      measure in acute pain trials.

PMID- 23167634
TI  - Echocardiography and coronary CT angiography imaging of variations in coronary
      anatomy and coronary abnormalities in athletic children: detection of coronary
      abnormalities that create a risk for sudden death.
AB  - In a recent publication, Maron et al. reported the causes of sudden death in
      athletes from data collected in the US National Registry of Sudden Death in
      Athletes at the Minneapolis Heart Institute Registry. It is not surprising that
      in this study, cardiovascular disease is reported as the most common cause of
      sudden death in athletes (56%). The most frequently encountered cardiac pathology
      was hypertrophic cardiomyopathy (36% of the population who died of cardiac
      disease). Coronary artery anomalies of wrong sinus origin were next in frequency
      (17%). Less common causes attributed to coronary pathology were Kawasaki disease,
      origin of the left coronary artery from the pulmonary artery, atherosclerotic
      coronary artery disease, and myocardial bridging of the left anterior descending
      artery. Echocardiographic imaging along with color and pulsed-wave Doppler has
      been widely employed to visualize the anatomy and function of the heart and
      proves to be a valuable instrument in the identification of coronary artery
      abnormalities. Moreover, coronary CT angiography provides additional confirmatory
      information. This article will discuss the scope, importance, and implications of
      echocardiographic and coronary CT angiography imaging of the major coronary
      anomalies and abnormalities in young athletes who are at risk of sudden death and
      who otherwise have a structurally normal heart.

PMID- 23167635
TI  - Protein dynamics and ion traffic in bacterioferritin.
AB  - Bacterioferritin (Bfr) is a spherical protein composed of 24 subunits and 12 heme
      molecules. Bfrs contribute to regulate iron homeostasis in bacteria by capturing
      soluble but potentially toxic Fe(2+) and by compartmentalizing it in the form of
      a bioavailable ferric mineral inside the protein's hollow cavity. When iron is
      needed, Fe(3+) is reduced and mobilized into the cytosol as Fe(2+). Hence, key to
      the function of Bfr is its ability to permeate iron ions in and out of its
      interior cavity, which is likely imparted by a flexible protein shell. To examine
      the conformational flexibility of Bfrs in a native-like environment and the way
      in which the protein shell interacts with monovalent cations, we have performed
      molecular dynamics (MD) simulations of BfrB from Pseudomonas aeruginosa (Pa BfrB)
      in K(2)HPO(4) solutions at different ionic strengths. The results indicate the
      presence of coupled thermal fluctuations (dynamics) in the 4-fold pores and B
      pores of the protein, which is key to allowing passage of monovalent cations
      through the protein shell using B-pores as conduits. The MD simulations also show
      that Pa BfrB ferroxidase centers are highly dynamic and permanently populated by
      transient cations exchanging with other cations in the interior cavity, as well
      as the solution bathing the protein. Taken together, the findings suggest that
      Fe(2+) passes across the Pa BfrB shell via B-pores and that the ferroxidase pores
      allow the capture and oxidation of Fe(2+), followed by translocation of Fe(3+) to
      the interior cavity, aided by the conformationally active H130.

PMID- 23167636
TI  - Cytogenetic analysis of human cells reveals specific patterns of DNA damage in
      replicative and oncogene-induced senescence.
AB  - Senescence is thought to be triggered by DNA damage, usually indirectly assessed
      as activation of the DNA damage response (DDR), but direct surveys of genetic
      damage are lacking. Here, we mitotically reactivate senescent human fibroblasts
      to evaluate their cytogenetic damage. We show that replicative senescence is
      generally characterized by telomeric fusions. However, both telomeric and
      extratelomeric aberrations are prevented by hTERT, indicating that even non
      telomeric damage descends from the lack of telomerase. Compared with replicative
      senescent cells, oncogene-induced senescent fibroblasts display significantly
      higher levels of DNA damage, depicting how oncogene activation can catalyze the
      generation of further, potentially tumorigenic, genetic damage.

PMID- 23167637
TI  - Endoscopist's view of the future role of the gastroenterologist in digestive
      oncology.
AB  - Improvement in digestive oncology will require the creation of multidisciplinary
      teams. Expert gastroenterologists who are super-specializing in digestive
      oncology (onco-gastroenterologists) should be in the center of such highly
      qualified teams. To fulfill this role the onco-gastroenterologist will need
      adequate training in all aspects of diagnostic and therapeutic endoscopic
      activities related to digestive cancer. This article reflects the spectrum of
      expertise that will be necessary to guarantee optimal service.

PMID- 23167638
TI  - Donor specific transplant tolerance is dependent on complement receptors.
AB  - The complement system has recently been described as a crucial component for
      transplant tolerance induction, but the underlying mechanisms are poorly
      understood. Using a rodent model of donor lymphocyte infusion-induced male
      histocompatibility antigen-specific transplant tolerance, we demonstrate that
      tolerance induction is dependent on the complement receptors decay accelerating
      factor, complement receptor 3, and complement component 3a receptor (C3aR).
      Furthermore, we have provided evidence that complement dependent tolerance is
      mediated through C3aR on infused donor splenocytes and on recipient cells. Ex
      vivo studies showed that C3aR deficiency leads to an imbalance between T
      regulatory and T effector cells. Increased numbers of antigen-specific CD8(+) 
      cells in the blood and less T regulatory cells, with reduced suppressive
      function, in the spleen and in the skin grafts were detected in C3aR deficient
      compared to wild type mice. This imbalance might be explained by the requirement
      of complement for dendritic cells to generate T regulatory cells effectively. Our
      experiments suggest that multiple complement receptors play an important role in
      transplant tolerance induction providing new insights into the mechanisms of
      complement dependent tolerance.

PMID- 23167640
TI  - Consumer genetics and addiction susceptibility testing-just what the consumer
      ordered.

PMID- 23167639
TI  - The decision-making process of young adult women with cancer who considered
      fertility cryopreservation.
AB  - OBJECTIVE: To provide an in-depth description of the decision-making process that
      women who are diagnosed with cancer undergo as they decide whether to accept or
      decline fertility cryopreservation. DESIGN: A qualitative, grounded theory
      approach. SETTING AND PARTICIPANTS: Twenty-seven women (mean age = 29 years) who
      were diagnosed with cancer and were eligible for egg, embryo, or ovarian tissue
      cryopreservation were recruited from the Internet and two university centers.
      METHODS: Each woman participated in a semistructured interview by phone (n = 21)
      or e-mail (n = 6). Data were analyzed using the constant-comparative method to
      inductively ascertain the women's decision-making process. NVivo 8 software was
      used to assist with data retrieval and analysis. RESULTS: The decision-making
      process consists of four major phases that women experience to actively formulate
      a decision: identify, contemplate, resolve, and engage. In the identify phase,
      women acquire knowledge and experience a "double hit" scenario that is often
      devastating. Within the contemplate phase, five interrelated dimensions emerged
      including constructing and/or endorsing preferences and values and undergoing
      decisional debriefing sessions. A decision is reached in the resolve phase and
      carried out in the engage phase. Among the participants, 14 declined fertility
      cryopreservation and 13 accepted egg and/or embryo cryopreservation. CONCLUSION:
      The descriptive theoretical framework clarifies the underlying processes that
      women with cancer undergo to decide about fertility cryopreservation. Quality of
      care for women with cancer can be improved by implementing appropriately timed
      information and tailored developmental and contextual counseling to support
      decision making.

PMID- 23167641
TI  - Debating the clinical utility of direct-to-consumer genetic testing for addiction
      susceptibility.

PMID- 23167642
TI  - Testing times.

PMID- 23167643
TI  - Addiction science, meet translational genomics.

PMID- 23167644
TI  - Response to commentaries: Slowing down the rush to translation in personal
      genomics.

PMID- 23167645
TI  - Commentary on Des Jarlais et al. (2012): are ethnic disparities in drug policy
      related harms relevant to the addiction medicine community?

PMID- 23167646
TI  - Commentary on Ondersma et al. (2012): beyond the quest for the perfect test-drug
      use screening in pregnancy.

PMID- 23167647
TI  - Commentary on McCarthy et al. (2012): understanding how alcohol affects decisions
      to drive while intoxicated-the need to deconstruct impulsivity.

PMID- 23167648
TI  - Commentary on Gates et al. (2012): Telehealth services to extend the reach of
      care involve more than using a telephone for intervention delivery.

PMID- 23167649
TI  - Commentary on Durkee et al. (2012): adolescents in a webbed world.

PMID- 23167650
TI  - Griffith Edwards (1928-2012).

PMID- 23167652
TI  - Piscine reovirus (PRV) in wild Atlantic salmon, Salmo salar L., and sea-trout,
      Salmo trutta L., in Norway.
AB  - This is the first comprehensive study on the occurrence and distribution of
      piscine reovirus (PRV) in Atlantic salmon, Salmo salar L., caught in Norwegian
      rivers. PRV is a newly discovered reovirus associated with heart and skeletal
      muscle inflammation (HSMI), a serious and commercially important disease
      affecting farmed Atlantic salmon in Norway. A cross-sectional survey based on
      real-time RT-PCR screening of head kidney samples from wild, cultivated and
      escaped farmed Atlantic salmon caught from 2007 to 2009 in Norwegian rivers has
      been conducted. In addition, anadromous trout (sea-trout), Salmo trutta L.,
      caught from 2007 to 2010, and anadromous Arctic char, Salvelinus alpinus (L.),
      caught from 2007 to 2009, were tested. PRV was detected in Atlantic salmon from
      all counties included in the study and in 31 of 36 examined rivers. PRV was also
      detected in sea-trout but not in anadromous Arctic char. In this study, the mean
      proportion of PRV positives was 13.4% in wild Atlantic salmon, 24.0% in salmon
      released for stock enhancement purposes and 55.2% in escaped farmed salmon.
      Histopathological examination of hearts from 21 PRV-positive wild and one
      cultivated salmon (Ct values ranging from 17.0 to 39.8) revealed no HSMI-related
      lesions. Thus, it seems that PRV is widespread in Atlantic salmon returning to
      Norwegian rivers, and that the virus can be present in high titres without
      causing lesions traditionally associated with HSMI.

PMID- 23167653
TI  - Bombesin peptide antagonist for target-selective delivery of liposomal
      doxorubicin on cancer cells.
AB  - Purpose: This study addresses novel peptide modified liposomal doxorubicin to
      specifically target tissues overexpressing bombesin (BN) receptors.   Methods:
      DOTA-(AEEA)(2)-peptides containing the [7-14]bombesin and the new BN-AA1 sequence
      have been synthesized to compare their binding properties and in serum
      stabilities. The amphiphilic peptide derivative (MonY-BN-AA1) containing BN-AA1,
      a hydrophobic moiety, polyethylenglycole (PEG), and
      diethylenetriaminepentaacetate (DTPA), has been synthesized. Liposomes have been
      obtained by mixing of MonY-BN-AA1 with 1,2-distearoyl-sn-glycero-3-phosphocholine
      (DSPC).   Results: Both (111)In labeled peptide derivatives present nanomolar Kd
      to PC-3 cells. (177)Lu labeled peptide DOTA-(AEEA)(2)-BN-AA1 is very stable (half
      life 414.1 h), while DOTA-(AEEA)(2)-BN, shows a half-life of 15.5 h. In vivo
      studies on the therapeutic efficacy of DSPC/MonY-BN-AA1/Dox in comparison to
      DSPC/MonY-BN/Dox, were performed in PC-3 xenograft bearing mice. Both
      formulations showed similar tumor growth inhibition (TGI) compared to control
      animals treated with non-targeted DSPC/Dox liposomes or saline solution. For
      DSPC/MonY-BN-AA1/Dox the maximum effect was observed 19 days after treatment.  
      Conclusions: DSPC/MonY-BN-AA1/Dox nanovectors confirm the ability to selectively
      target and provide therapeutic efficacy in mice. The lack of receptor activation
      and possible acute biological side effects provided by using the AA1 antagonist
      bombesin sequence should provide safe working conditions for further development
      of this class of drug delivery vehicles.

PMID- 23167654
TI  - Development of second-generation indole-based dynamin GTPase inhibitors.
AB  - Focused library development of our lead 2-cyano-3-(1-(3-(dimethylamino)propyl)-2
      methyl-1H-indol-3-yl)-N-octylacrylamide (2) confirmed the tertiary dimethylamino
      propyl moiety as critical for inhibition of dynamin GTPase. The cyanoamide moiety
      could be replaced with a thiazole-4(5H)-one isostere (19, IC(50(dyn I)) = 7.7
      MUM), reduced under flow chemistry conditions (20, IC(50(dyn I)) = 5.2 MUM) or
      replaced by a simple amine. The latter provided a basis for a high yield library
      of compounds via a reductive amination by flow hydrogenation. Two compounds, 24
      (IC(50 (dyn I)) = 0.56 MUM) and 25 (IC(50(dyn I)) = 0.76 MUM), stood out. Indole
      24 is nontoxic and showed increased potency against dynamin I and II in vitro and
      in cells (IC(50(CME)) = 1.9 MUM). It also showed 4.4-fold selectivity for dynamin
      I. The indole 24 compound has improved isoform selectivity and is the most active
      in-cell inhibitor of clathrin-mediated endocytosis reported to date.

PMID- 23167655
TI  - Coenzyme Q10 inhibits the release of glutamate in rat cerebrocortical nerve
      terminals by suppression of voltage-dependent calcium influx and mitogen
      activated protein kinase signaling pathway.
AB  - This study investigates the effects and possible mechanism of coenzyme Q10
      (CoQ10) on endogenous glutamate release in the cerebral cortex nerve terminals of
      rats. CoQ10 inhibited the release of glutamate evoked by the K+ channel blocker 4
      aminopyridine (4-AP). CoQ10 reduced the depolarization-induced increase in
      cytosolic [Ca2+]c but did not alter the 4-AP-mediated depolarization. The effect
      of CoQ10 on evoked glutamate release was abolished by blocking the Cav2.2 (N
      type) and Cav2.1 (P/Q-type) Ca2+ channels and mitogen-activated protein kinase
      kinase (MEK). In addition, CoQ10 decreased the 4-AP-induced phosphorylation of
      extracellular signal-regulated kinase 1 and 2 (ERK1/2) and synaptic vesicle
      associated protein synapsin I, a major presynaptic substrate for ERK. Moreover,
      the inhibition of glutamate release by CoQ10 was strongly attenuated in mice
      without synapsin I. These results suggest that CoQ10 inhibits glutamate release
      from cortical synaptosomes in rats through the suppression of the presynaptic
      voltage-dependent Ca2+ entry and ERK/synapsin I signaling pathway.

PMID- 23167656
TI  - Delay in discharge and its impact on unnecessary hospital bed occupancy.
AB  - BACKGROUND: Elderly patients are potentially more vulnerable to prolonged
      hospital stay as they frequently require additional resources to facilitate their
      discharge. In an acute hospital setting, we aimed to quantify and compare length
      of stay (LOS) for all patients over and under the age of 65, and identify the
      number and cause of days lost under the care of a single surgical unit. METHODS:
      Over a 4 month period from January to April 2010, data on the management and
      source of potential delay was collected daily on consecutive patients admitted
      and discharged under the care of one consultant surgeon at a district general
      hospital. Statistical analysis was then performed with particular focus on actual
      delays affecting elderly patients. RESULTS: A total of 99 complete inpatients
      episodes were recorded. There were 30 elective and 69 acute admissions. 10 (33%)
      elective vs. 42 (61%) acute patients encountered delays, losing 39 and 232 days
      respectively (chi2 [1, N = 99] = 6.36, p = .012). 23 of a total 39 elderly
      patients admitted acutely required specialist care of the elderly opinion and
      placement in community hospitals resulting in delays of 188 days. vs. 36 days for
      the 16 discharged home and 8 days for 30 patients under 65 (chi2 (2, N = 69) =
      26.54, p = <.001). CONCLUSIONS: Elderly patients experiencing acute surgical
      admission and discharge to community hospitals had prolonged LOS due to
      significant delays associated with care of the elderly provision. The financial
      considerations behind bed capacity in primary and secondary care and the
      provision of care of elderly services need to be balanced against unnecessary
      occupancy of acute hospital beds with its associated health and economic
      implications.

PMID- 23167657
TI  - Novel para-aortic lymphadenectomy technique for gynecological malignancies
      prevents postoperative bowel obstruction.
AB  - AIM: The aim of this study was to evaluate the effect of our novel technique on
      the prevention of postoperative ileus in patients undergoing systematic para
      aortic lymphadenectomy (PALN). MATERIAL AND METHODS: PALN was performed in 135
      gynecological cancer patients (67 with ovarian cancer, 58 with endometrial
      cancer, 8 with serous surface papillary adenocarcinoma (SSPC) and 2 with
      fallopian tube cancer) between 2006 and 2011. To prevent postoperative ileus, we
      performed our novel technique wherein the small bowel and colon are released from
      pressure and soaked in 2 L of physiological saline for 1 min every 20 min during
      the lymphadenectomy. We indicated our novel PALN technique and retrospectively
      analyzed the outcomes of the surgical procedure in terms of the surgical data,
      and postoperative incidence of gastrointestinal dysfunction in patients with
      gynecological malignancies. RESULTS: The mean blood loss was 641.2 +/- 800.3 mL
      in the PALN group and 313.9 +/- 278.9 mL in the pelvic lymphadenectomy (PLN)
      without PALN group (P < 0.0001). There was no difference in the first passage of
      flatus between the PALN group and the PLN group (1.8 +/- 0.7 days vs 1.6 +/- 0.7
      days). The mean time to tolerance of a regular diet was significantly longer in
      the PALN group than in the PLN group (P < 0.0001), whereas the incidence of
      vomiting was similar in both groups. Surprisingly, there were no cases of
      postoperative ileus in either group. CONCLUSION: Our novel technique is a safe
      and effective way to prevent the incidence and decrease the severity of
      postoperative ileus after PALN for gynecological malignancies.

PMID- 23167658
TI  - Modeling gradually changing seasonal variation in count data using state space
      models: a cohort study of hospitalization rates of stroke in atrial fibrillation
      patients in Denmark from 1977 to 2011.
AB  - BACKGROUND: Seasonal variation in the occurrence of cardiovascular diseases has
      been recognized for decades. In particular, incidence rates of hospitalization
      with atrial fibrillation (AF) and stroke have shown to exhibit a seasonal
      variation. Stroke in AF patients is common and often severe. Obtaining a
      description of a possible seasonal variation in the occurrence of stroke in AF
      patients is crucial in clarifying risk factors for developing stroke and
      initiating prophylaxis treatment. METHODS: Using a dynamic generalized linear
      model we were able to model gradually changing seasonal variation in
      hospitalization rates of stroke in AF patients from 1977 to 2011. The study
      population consisted of all Danes registered with a diagnosis of AF comprising
      270,017 subjects. During follow-up, 39,632 subjects were hospitalized with
      stroke. Incidence rates of stroke in AF patients were analyzed assuming the
      seasonal variation being a sum of two sinusoids and a local linear trend.
      RESULTS: The results showed that the peak-to-trough ratio decreased from 1.25 to
      1.16 during the study period, and that the times of year for peak and trough
      changed slightly. CONCLUSION: The present study indicates that using dynamic
      generalized linear models provides a flexible modeling approach for studying
      changes in seasonal variation of stroke in AF patients and yields plausible
      results.

PMID- 23167659
TI  - The genetics of type 2 diabetes and its clinical relevance.
AB  - The increasing worldwide prevalence of type 2 diabetes (T2D) motivates efforts to
      use genetics to define key pathways involved in disease predisposition, and
      thereby to improve management of the disease. Research over the past 5 years has
      taken the total number of genetic loci implicated in T2D susceptibility beyond
      60, and the emphasis is now shifting to the translation of these genetic insights
      into clinical value. Clinical translation may flow from the identification of
      novel therapeutic targets, but opportunities also exist with respect to
      individual prediction, diagnostic biomarkers and therapeutic optimization. To
      date, the main clinical impact has been seen for relatively rare, monogenic forms
      of diabetes rather than common T2D. However, the advent of high throughput
      sequencing approaches may herald discovery of rare and low frequency variants
      that offer greater translational potential.

PMID- 23167660
TI  - Modelling of global boundary effects on harmonic motion imaging of soft tissues.
AB  - Biomechanical imaging techniques have been developed for soft tissue
      characterisation and detection of breast tumours. Harmonic motion imaging (HMI)
      uses a focused ultrasound technology to generate a harmonic radiation force in a
      localised region inside a soft tissue. The resulting dynamic response is used to
      map the local distribution of the mechanical properties of the tissue. In this
      study, a finite element (FE) model is developed to investigate the effect of
      global boundary conditions on the dynamic response of a soft tissue during HMI.
      The direct-solution steady-state dynamic analysis procedure is used to compute
      the harmonic displacement amplitude in FE simulations. The model is parameterised
      in terms of boundary conditions and viscoelastic properties, and the
      corresponding raster-scan displacement amplitudes are captured to examine its
      response. The effect of the model's global dimensions on the harmonic response is
      also investigated. It is observed that the dynamic response of soft tissue with
      high viscosity is independent of the global boundary conditions for regions
      remote to the boundary; thus, it can be subjected to local analysis to estimate
      the underlying mechanical properties. However, the dynamic response is sensitive
      to global boundary conditions for tissue with low viscosity or regions located
      near to the boundary. 

PMID- 23167661
TI  - Interactive team cognition.
AB  - Cognition in work teams has been predominantly understood and explained in terms
      of shared cognition with a focus on the similarity of static knowledge structures
      across individual team members. Inspired by the current zeitgeist in cognitive
      science, as well as by empirical data and pragmatic concerns, we offer an
      alternative theory of team cognition. Interactive Team Cognition (ITC) theory
      posits that (1) team cognition is an activity, not a property or a product; (2)
      team cognition should be measured and studied at the team level; and (3) team
      cognition is inextricably tied to context. There are implications of ITC for
      theory building, modeling, measurement, and applications that make teams more
      effective performers.

PMID- 23167662
TI  - Maternal and child dietary patterns and their determinants in Nigeria.
AB  - Understanding the overall dietary patterns of a population is a key step in
      initiating appropriate nutritional interventions and policies. Studies
      characterising the dietary patterns of Nigerian mothers and children are lacking.
      Complete dietary data for 13,566 mothers and their 13,506 children were analysed
      from the 2008 Nigerian Demographic and Health Surveys (NDHS), a nationally
      representative sample, to identify the overall maternal and child dietary
      patterns and to study the potential determinants of such dietary patterns. The
      2008 NDHS included questions that inquired about the food items mothers and their
      children had consumed during the 24 h preceding the day of the interview. Factor
      analysis with the principal component procedure was used to construct the dietary
      patterns, and multiple multilevel logistic regression was used to investigate the
      determinants of the dietary patterns. Four ('mixed', 'traditional', 'staple foods
      and milk products' and 'beverages') and five ('mixed', 'selective', 'beverages
      and candies', 'gruels, grains and semi-solids' and 'infant formula and cereals')
      distinct dietary patterns were obtained for the mothers and children,
      respectively. The key determinants of both maternal and child dietary patterns
      were month of interview, religion, region of residence, maternal education,
      maternal occupation, wealth index and maternal body mass index. Marital status
      additionally predicted maternal patterns, while sex of the child, number of
      siblings, child's age, maternal age and place of residence additionally
      determined the child's patterns. This study has identified four and five
      different dietary patterns to characterise the dietary habits of Nigerian mothers
      and their children, respectively, and has shown the important socio
      economic/demographic factors influencing the dietary patterns, which can guide
      appropriate nutritional interventions among Nigerian mothers and children.

PMID- 23167663
TI  - Supramolecular rotators of (aniliniums)([18]crown-6) in electrically conducting
      [Ni(dmit)2] crystals.
AB  - Supramolecular assemblies of anilinium (Ani(+)) and fluoroanilinium derivatives
      (FAni(+)) with [18]crown-6 were introduced into electrically conducting
      [Ni(dmit)(2)] crystals (dmit(2-) is 2-thioxo-1,3-dithiole-4,5-dithiolate). The
      crystal structures, electrical conductivities, and magnetic susceptibilities of
      four new crystals of (Ani(+))([18]crown-6)[Ni(dmit)(2)](3) (1), (o
      FAni(+))([18]crown-6)[Ni(dmit)(2)](3) (2), (m-FAni(+))([18]crown
      6)[Ni(dmit)(2)](3) (3), and (p-FAni(+))([18]crown-6)[Ni(dmit)(2)](3) (4) were
      examined from the viewpoint of dynamic supramolecular rotator structures within
      the crystals. The crystal structures, electrical conduction, and magnetic
      properties were classified into group-I (crystals 1 and 4) and group-II (crystals
      2 and 3). The hydrogen-bonding interaction between -NH(3)(+) and the oxygen atoms
      of [18]crown-6 formed the stand-up configuration of rotator-stator structures of
      (Ani(+))([18]crown-6) and (FAni(+))([18]crown-6) supramolecules. The potential
      energy barriers for the 2-fold flip-flop motion of phenyl- and p-fluorophenyl
      rings in crystals 1 and 4 had a relatively small magnitude of ~150 kJ mol(-1),
      suggesting that rotations of Ani(+) and p-FAni(+) cations around the C-NH(3)(+)
      axis occurred in the crystals. In contrast, a large magnitude of the potential
      energy barriers for the rotations of o-FAni(+) and m-FAni(+) cations in crystals
      2 and 3 (>600 kJ mol(-1)) resulted in static supramolecular cationic structures.
      The cation:anion ratio of 1:3 in these crystals yielded a trimer pi-stack of
      [Ni(dmit)(2)] with a semiconductor-like temperature dependence. The magnetic
      susceptibilities of the static crystals 2 and 3 were reproduced by the one
      dimensional antiferromagnetic linear Heisenberg chain through the one-dimensional
      linear trimer arrangement. The magnetic susceptibilities of dynamic crystals 1
      and 4 enhanced electron delocalization through the intratrimer and intertrimer
      interactions within the trimer stack, where the molecular rotations of Ani(+) and
      p-FAni(+) cations played an important role.

PMID- 23167664
TI  - Accidental clozapine intoxication in a toddler: clinical and pharmacokinetic
      lessons learnt.
AB  - WHAT IS KNOWN AND OBJECTIVE: Clozapine, a second generation antipsychotic which
      is relatively safe in overdose, has been used as an effective treatment
      alternative to traditional antipsychotics. The therapeutic use in children
      remains controversial. However, in accordance with the increasing prescription in
      adults, the accidental ingestion in childhood becomes more frequent. We report
      the youngest case of accidental clozapine ingestion. CASE SUMMARY: A 13-month-old
      girl presented with acute respiratory insufficiency and coma of unknown origin.
      The medical history, laboratory and radiological assessment did not link to
      aetiology until an almost spontaneous arousal after 22 h pointed towards
      intoxication. The initial standard drug screening using immunoassay had been
      negative. Hence, liquid chromatography mass spectrometry/mass spectrometry (LC
      MS/MS) was performed, and clozapine was detected with a serum concentration of
      736 ng/mL. WHAT IS NEW AND CONCLUSION: This case illustrates the diagnostic and
      forensic pitfalls in a coma of unknown origin due to the limits of toxicological
      screening immunoassays. LC-MS/MS analysis by an established method showed
      clozapine metabolites (norclozapine and clozapine-N-oxide) are detectable for
      longer period, especially in urine, when compared with clozapine. The clinical
      course is presented in unique correlation with plasma and urine concentrations of
      clozapine and its metabolites. The elimination pattern of clozapine in toddlers
      is similar to adults, and the toxic dose was found to be lower when compared with
      school-age children and adults.

PMID- 23167665
TI  - Current update in the management of diabetic nephropathy.
AB  - Diabetic nephropathy is the leading cause of end-stage renal disease in the
      United States. The progression of kidney disease in patients with diabetes can
      take many years, and interventions such as glycemic control, blood pressure
      control, and inhibition of the renin-angiotensin-aldosterone system have been
      shown to slow this progression. Despite the implementation of these strategies,
      the number of patients with diabetes that ultimately develop end-stage renal
      disease remains high. Recent investigation has focused on the optimization of
      renin-angiotensin-aldosterone system blockade in patients with diabetic
      nephropathy using combinations of drugs that target this pathway. Additional
      investigation has focused on the potential of novel therapies that either target
      various pathways upregulated by hyperglycemia or other targets believed to
      promote progression of diabetic nephropathy such as the endothelin system,
      inflammation and vitamin D receptors. This review article addresses some of the
      well-established principles regarding the progression and accepted management of
      diabetic nephropathy and includes current updates on the most recent clinical
      research trials exploring novel therapeutics in this field.

PMID- 23167666
TI  - Surprising outcome of ommaya reservoir in treating cystic craniopharyngioma: a
      retrospective study.
AB  - BACKGROUND: Surgical removal (gross total or partial removal), radiotherapy and
      cyst evacuation have all been used individually or in combination to treat cystic
      craniopharyngioma, although it is unclear which is the best method. OBJECTIVE: To
      report the results of treating cystic craniopharyngioma by insertion of an Ommaya
      reservoir system (ORS) and aspiration of the cyst. PATIENTS AND METHODS: As from
      1990, patients admitted to the neurosurgical department at Assiut University
      Hospital, Egypt, with grossly cystic craniopharyngioma and who had a single cyst
      and did not have previous surgery were treated by insertion of an ORS and
      drainage of the cyst. By 2010, 52 patients had received this treatment with the
      cystic fluid aspirated completely on the day of surgery. The main presenting
      symptoms were raised intracranial pressure and visual changes with hormonal
      changes observed in some patients. The minimal follow-up period was 7 years.
      RESULTS: To our surprise, 38 (73%) patients did not develop any recollection of
      the cyst and showed significant clinical improvement. The only possible
      explanation is that the part of the catheter of the ORS, with holes in, has
      established communication between the cyst and the CSF spaces around it after the
      collapse of the cyst with no adverse effect on the patient at any time. Ten (19%)
      patients needed reaspiration every 6 months and four (8%) patients showed rapid
      recollection of cystic fluid and were treated with intracystic bleomycin.
      CONCLUSION: Treatment of cystic craniopharyngioma by drainage through an ORS is
      very effective. The majority of patients do not need any further treatment. Those
      who develop re-accumulation of cystic fluid are easily treated by simple
      aspiration of the fluid through the reservoir. It is a simple and safe method,
      which lacks the risks associated with surgery or chemotherapy.

PMID- 23167667
TI  - Isolated neurosarcoidosis in the medulla oblongata involving the fourth
      ventricle: a case report.
AB  - We report a 61-year-old woman with definite diagnosis of isolated
      neurosarcoidosis in the medulla oblongata involving the fourth ventricle. We
      could not recognize neurosarcoidosis as one of the differential diagnoses of the
      lesion before biopsy because the brainstem lesion location and periventricular
      lesion configuration were quite unusual.

PMID- 23167668
TI  - Meningioangiomatosis in a patient with progressive focal neurological deficit
      case report and review of literature.
AB  - Meningioangiomatosis (MA) represents a vascular hamartoma accompanied by
      meningothelial cell proliferation. It generally becomes symptomatic with
      difficult to control seizures, though in some patients it may be asymptomatic. We
      present the case of a 41-year-old male patient with a newly developed central
      distal monoparesis of the left leg. Cranial magnetic resonance imaging (MRI) and
      further diagnostic characterization via (18)F-Fluoro-Ethyl-Tyrosine positron
      emission tomography ((18)F-FET-PET) indicated a low-grade glioma.
      Histopathological diagnosis revealed a meningioangiomatosis. The clinical,
      radiological and neuropathological findings of this rare constellation are
      described and discussed with the actual literature.

PMID- 23167670
TI  - One-dimensional quantum confinement effect modulated thermoelectric properties in
      InAs nanowires.
AB  - We report electrical conductance and thermopower measurements on InAs nanowires
      synthesized by chemical vapor deposition. Gate modulation of the thermopower of
      individual InAs nanowires with a diameter around 20 nm is obtained over T = 40
      300 K. At low temperatures (T < ~100 K), oscillations in the thermopower and
      power factor concomitant with the stepwise conductance increases are observed as
      the gate voltage shifts the chemical potential of electrons in InAs nanowire
      through quasi-one-dimensional (1D) subbands. This work experimentally shows the
      possibility to modulate semiconductor nanowire's thermoelectric properties
      through 1D subband formation in the diffusive transport regime for electron, a
      long-sought goal in nanostructured thermoelectrics research. Moreover, we point
      out the scattering (or disorder) induced energy level broadening as the limiting
      factor in smearing out the 1D confinement enhanced thermoelectric power factor.

PMID- 23167669
TI  - Polymer separators for high-power, high-efficiency microbial fuel cells.
AB  - Microbial fuel cells (MFCs) with hydrophilic poly(vinyl alcohol) (PVA) separators
      showed higher Coulombic efficiencies (94%) and power densities (1220 mW m(-2))
      than cells with porous glass fiber separators or reactors without a separator
      after 32 days of operation. These remarkable increases in both the coublomic
      efficiency and the power production of the microbial fuel cells were made
      possible by the separator's unique characteristics of fouling mitigation of the
      air cathode without a large increase in ionic resistance in the cell. This new
      type of polymer gel-like separator design will be useful for improving MFC
      reactor performance by enabling compact cell designs.

PMID- 23167671
TI  - Three-component, one-pot sequential synthesis of functionalized cyclazines: 3H
      1,2a1,3-triazaacenaphthylenes.
AB  - An efficient tandem route to the synthesis of 3H-1,2a(1),3-triazaacenaphthylene
      derivatives of the cyclazine family has been developed. Target compounds were
      obtained in moderate to good yields by a Yb(OTf)(3)/Ag(2)CO(3)-catalyzed, three
      component domino reaction. This in turn will set the stage for a wide application
      of this useful reaction for the synthesis of structurally diverse
      polyheterocyclic skeletons containing the imidazo[1,2-a]pyridine privileged
      structure.

PMID- 23167672
TI  - Experiences of parents whose newborns undergo hypothermia treatment following
      perinatal asphyxia.
AB  - OBJECTIVE: To describe and interpret experiences of parents whose newborns are
      treated with induced hypothermia following perinatal asphyxia. DESIGN: A
      qualitative exploratory study. SETTING: Data collection in parental home
      environments (n = 8) and in a study room in a university library (n = 2).
      PARTICIPANTS: A total of 10 parents, seven mothers and three fathers,
      participated in the study. Their newborns were treated with induced hypothermia 4
      to 12 months prior to the interviews. METHODS: Recorded open-ended interviews
      with the participants lasted from 60 to 90 minutes. Field notes were made after
      each interview. The interviews were transcribed verbatim and inductive content
      analysis was used in the analyzing process. RESULTS: Four main themes emerged
      from the data: emotional landscapes, adaptation to a new situation (with
      subthemes creating control, external and internal support in a difficult
      situation, normalizing the abnormal and reconciling oneself to uncertainty),
      moments of rebirth, and change in attitude toward life and existence. CONCLUSION:
      Term newborns are treated with induced hypothermia treatment due to perinatal
      asphyxia. During the hospitalization of newborns in neonatal intensive care units
      (NICUs), parents experience high levels of stress. Parents use several strategies
      for adapting to this situation, and nurses play a pivotal role in providing
      individual support and acting as advocates for parents in the NICU. After the
      infants are rewarmed, parents experience a moment of rebirth that might help them
      attach to their infants. Further research is warranted in this area to provide
      holistic care and support to families whose neonates undergo this treatment.

PMID- 23167673
TI  - Study on drug costs associated with COPD prescription medicine in Denmark.
AB  - INTRODUCTION: Spirometric studies of the general population estimate that 430 000
      Danes have chronic obstructive pulmonary disease (COPD). COPD is mainly caused by
      smoking, and smoking cessation is the most important intervention to prevent
      disease progression. Cost-of-illness studies conclude that the costs associated
      with COPD in Denmark are significant, but costs of prescription medicine for COPD
      were not analysed. OBJECTIVES: To analyse the societal costs associated with
      prescription medicine for COPD in Denmark. METHODS: The study was designed as a
      nationwide retrospective register study of the drug costs (ATC group R03)
      associated with COPD in the period 2001-2010. Data were retrieved from the
      Prescription Database, the National Patient Register and the Centralised Civil
      Register. The population comprised individuals (40+ years) who had at least one
      prescription of selected R03 drugs and who had been either hospitalised with a
      COPD diagnosis or had at least one prescription for drugs primarily used for
      COPD. RESULTS: The study population comprised 166 462 individuals of which 97 916
      were alive on 31 December 2010. The average annual drug costs (R03) were DKK 7842
      (EUR 1055) per patient in 2010 with total costs of DKK 685 million (EUR 92
      million). The average lifetime costs associated with COPD prescription medicine
      were estimated to be DKK 70 000-75 000 (EUR 9416-10 089) per patient (2010
      prices). CONCLUSION: The costs associated with prescription medicine for COPD in
      Denmark are significant.

PMID- 23167674
TI  - Social relationships and subsequent health-related behaviours: linkages between
      adolescent peer status and levels of adult smoking in a Stockholm cohort.
AB  - AIMS: Peer status reflects the extent to which an individual is accepted by the
      group. Some studies have reported that low peer status in adolescence is
      associated with a higher risk of smoking, while others found the reverse. No
      studies have investigated peer status influences on adult smoking. The aim of the
      study was therefore to examine the relationship between adolescents' peer status
      and the intensity of smoking in adulthood. DESIGN: Prospective cohort study.
      SETTING: Stockholm, Sweden. PARTICIPANTS: A subsample (n = 2329) of the cohort
      with information about adult smoking. MEASUREMENTS: Peer status was assessed
      sociometrically at age 13 and information on smoking was gathered through a
      questionnaire at age 32. Relative risks (RR) for self-reported level of smoking
      were calculated using multinomial logistic regression. Several family-related and
      individual variables were included as control variables. FINDINGS: Lower peer
      status in adolescence was associated with smoking of any intensity in adulthood.
      For example, the risk of heavy smoking was more than threefold (RR = 3.67) among
      individuals in the lowest status positions. The association with occasional
      smoking was abolished by controlling for factors related to adolescents' attitude
      to school and cognitive ability. For regular and heavy smoking the relationship
      was attenuated by controlling for these factors. CONCLUSIONS: Low peer status in
      adolescence appears to be a risk factor for smoking in adulthood. Part of this
      association may be explained by adolescents' feelings towards school and
      cognitive ability. However, being unpopular in adolescence remains a strong risk
      factor for regular and heavy smoking in adulthood.

PMID- 23167676
TI  - Biodegradable hyperbranched amphiphilic polyurethane multiblock copolymers
      consisting of poly(propylene glycol), poly(ethylene glycol), and polycaprolactone
      as in situ thermogels.
AB  - This paper reports the synthesis and characterization of new hyperbranched
      amphiphilic polyurethane multiblock copolymers consisting of poly(propylene
      glycol) (PPG), poly(ethylene glycol) (PEG), and polycaprolactone (PCL) segments
      as in situ thermogels. The hyperbranched poly(PPG/PEG/PCL urethane)s, termed as
      HBPEC copolymers, were synthesized from PPG-diol, PEG-diol, and PCL-triol by
      using 1,6-hexamethylene diisocyanate (HMDI) as a coupling agent. The compositions
      and structures of HBPEC copolymers were determined by GPC and 1H NMR
      spectroscopy. We carried out comparative studies of the new hyperbranched
      copolymers with their linear counterparts, the linear poly(PPG/PEG/PCL urethane)
      (LPEC) copolymer and Pluronic F127 PEG-PPG-PEG block copolymer, in terms of their
      self-assembly and aggregation behaviors and thermoresponsive properties. HBPEC
      copolymers were found to show thermoresponsive micelle formation and aggregation
      behaviors. Particularly, the lower critical solution temperature (LCST) of the
      copolymers was significantly affected by the copolymer architecture. HBPEC
      copolymers showed much lower LCST than LPEC, the linear counterpart. Our studies
      revealed that the effect of hyperbranch architecture was more prominent in the
      gelation of the copolymers. The aqueous solutions of HBPEC copolymers exhibited
      thermogelling behaviors at critical gelation concentrations (CGCs) ranging from
      4.3 to 7.4 wt %. These values are much lower than those reported on other PCL
      contained linear thermogelling copolymers and Pluronic F127 copolymer. In
      addition, the CGC of HBPEC copolymers is much lower than the control LPEC
      copolymer. More interestingly, at high temperatures, while LPEC and other linear
      thermogelling copolymers formed turbid sol, HBPEC formed a dehydrated gel. Our
      data suggest that these phenomena are caused by the hyperbranched structure of
      HBPEC copolymers, which could increase the interaction of copolymer branches and
      enhance the chain association through synergetic hydrogen bonding effect. The
      thermogelling behavior of HBPEC block copolymers was further evidenced by the 1H
      NMR molecular dynamic study and rheological study, which further support the
      above hypothesis. The hydrolytic degradation study showed that the HBPEC
      copolymer hydrogels are biodegradable under physiological conditions. Together
      with the good cell biocompatibility demonstrated by the cytotoxicity study, the
      new thermogelling copolymers reported in this paper could potentially be used as
      in situ-forming hydrogels for biomedical applications.

PMID- 23167675
TI  - Nonassociative plasticity alters competitive interactions among mixture
      components in early olfactory processing.
AB  - Experience-related plasticity is an essential component of networks involved in
      early olfactory processing. However, the mechanisms and functions of plasticity
      in these neural networks are not well understood. We studied nonassociative
      plasticity by evaluating responses to two pure odors (A and X) and their binary
      mixture using calcium imaging of odor-elicited activity in output neurons of the
      honey bee antennal lobe. Unreinforced exposure to A or X produced no change in
      the neural response elicited by the pure odors. However, exposure to one odor
      (e.g. A) caused the response to the mixture to become more similar to that of the
      other component (X). We also show in behavioral analyses that unreinforced
      exposure to A caused the mixture to become perceptually more similar to X. These
      results suggest that nonassociative plasticity modifies neural networks in such a
      way that it affects local competitive interactions among mixture components. We
      used a computational model to evaluate the most likely targets for modification.
      Hebbian modification of synapses from inhibitory local interneurons to projection
      neurons most reliably produced the observed shift in response to the mixture.
      These results are consistent with a model in which the antennal lobe acts to
      filter olfactory information according to its relevance for performing a
      particular task.

PMID- 23167677
TI  - Utilizing three-dimensional echocardiography in cardioscopic left ventricular
      myxoma resection.
AB  - A 31-year-old female presented with right-sided stroke symptoms. She was found to
      have a left ventricular (LV) mass on transthoracic echocardiogram. Subsequent
      transesophageal echocardiogram (TEE) with concurrent three-dimensional (3D)
      imaging revealed a 2-cm mobile mass, suspicious for a myxoma, attached to the
      anteroseptal LV wall. Given the size and location of the mass seen on the 3D
      images, the cardiothoracic surgeons chose to avoid resection via aortotomy or
      ventriculotomy and instead performed video-assisted cardioscopic resection of the
      LV mass via left atriotomy. The mass was successfully removed, and pathology
      confirmed that it was a myxoma.

PMID- 23167678
TI  - Effect of low direct current on anaerobic multispecies biofilm adhering to a
      titanium implant surface.
AB  - PURPOSE: Peri-implantitis is caused by biofilm adhering to the implant. It has
      been shown that bactericidal electrolysis products are generated when a low
      direct current is applied to a titanium implant used as the anode. The hypothesis
      of this study was that low-current electrolysis would eradicate viable bacteria
      in a simulated subgingival multispecies biofilm adhering to a titanium implant
      surface. MATERIAL AND METHODS: Biofilms consisting of eight anaerobic species
      were grown on pellicle-coated titanium discs with sand-blasted, acid-etched,
      large-grit (SLA; Straumann, Basel, Switzerland) surface. After 40.5 hours of
      growth, discs were treated with 10 mA for 10 minutes in an electrolytical setup
      with physiological saline and gelatin. RESULTS: Low direct current at discs used
      as the cathode caused a reduction of three to four orders of magnitude in viable
      counts, while no viable bacteria were recovered from anode discs (Mann-Whitney U
      test, p < .01). Confocal laser scanning microscopy in combination with a
      live/dead stain showed biofilm detachment at the cathode and reduced viability at
      the anode. CONCLUSION: Electrochemical treatment of diseased implants appears to
      be promising and well worth investigating further.

PMID- 23167679
TI  - Glucocorticoid effects on skeletal muscle: benefit and risk in patients with
      autoimmune inflammatory rheumatoid diseases.

PMID- 23167680
TI  - From single-cell signature to prognostic factors: the case of Sezary syndrome.

PMID- 23167682
TI  - Clinical efficacy of icatibant in the treatment of acute hereditary angioedema
      during the FAST-3 trial.
AB  - Bradykinin is the key mediator of symptoms of hereditary angioedema (HAE), a rare
      genetic disorder characterized by recurrent episodes of edema of the skin, mucosa
      and muscle. Icatibant, a bradykinin B(2) receptor antagonist, is an effective and
      generally well-tolerated treatment option for acute attacks of type I and II HAE.
      A Phase III randomized, double-blind, placebo-controlled study, FAST-3
      (NCT00912093), was designed to further evaluate the efficacy and safety of
      icatibant in patients presenting with moderate to very severe cutaneous and/or
      abdominal or mild-to-moderate laryngeal symptoms. Severe laryngeal attacks were
      treated with open-label icatibant. The controlled phase of FAST-3, completed in
      October 2010 with results published in December 2011, demonstrated that compared
      with placebo, icatibant evoked clinically meaningful and statistically
      significant efficacy across multiple end points in the treatment of type I and II
      HAE attacks. In addition, icatibant was generally well tolerated and no drug
      related serious adverse events were experienced.

PMID- 23167683
TI  - Belatacept: a novel immunosuppressive agent for kidney transplant recipients.
AB  - Long-term graft and patient survival remain the most significant challenges in
      kidney transplantation, and new therapies are needed to improve long-term
      outcomes. Belatacept, a first-in-class selective costimulation blocker, has been
      approved for prophylaxis of organ rejection in kidney transplant recipients who
      are positive for EBV. In Phase III trials, belatacept demonstrated superior
      preservation of renal function and comparable patient/graft survival compared
      with cyclosporine, while avoiding the renal toxicities and other adverse events
      associated with the use of a calcineurin inhibitor. Patients treated with
      belatacept had higher rates of acute rejection than cyclosporine-treated
      patients. However, acute rejection episodes that occurred early and did not recur
      were generally not associated with donor-specific antibodies, and few belatacept
      patients had graft loss due to rejection. The improved renal benefit with
      belatacept may translate into improvements in long-term graft and patient
      outcomes. Targeting T-cell costimulation is an important new option for
      maintenance immunosuppression in kidney transplant recipients.

PMID- 23167684
TI  - An update on clinical immunology, immune mechanisms and deficiency diseases.
AB  - 29th Annual Jackson Hole, Wyoming, Update in Clinical Immunology, Microbiology
      and Infectious Diseases   Salt Lake city, UT, USA, 9-13 July 2012   The 29th
      Annual Jackson Hole, Wyoming, Update in Clinical Immunology, Microbiology and
      Infectious Diseases was held from 9 to 13 July 2012. This postgraduate,
      continuing medical education course of the University of Utah's Department of
      Pathology (UT, USA) is designed for laboratorians, clinical pathologists,
      pathologists, clinicians, clinical immunology and infectious disease specialists
      and medical technologists, as well as residents and fellows training in
      immunology, microbiology or infectious diseases.

PMID- 23167685
TI  - Adult versus pediatric eosinophilic esophagitis: important differences and
      similarities for the clinician to understand.
AB  - Eosinophilic esophagitis (EoE) is recognized as a common, allergy-associated
      cause of chronic esophageal symptoms affecting both children and adults. Research
      has begun to shed light on its epidemiology with consistent results from various
      geographical areas. Differences in clinical presentation, endoscopic aspects and
      response to treatment have all been reported for patients of different ages, and
      the question as to whether adult and pediatric EoE are manifestations of a single
      entity or in fact two distinct disorders has been posed. The most relevant
      differences between pediatric and adult EoE come from evolutionary changes in the
      consequences of the disease, including fibrous remodeling, and the ability to
      express symptoms. However, most studies support a common pathogenesis and similar
      histopathological features for adult and pediatric patients, being the same
      diagnostic criteria applied to them. This article comprehensively reviews the
      most recently published information and addresses important questions about the
      natural history of EoE.

PMID- 23167686
TI  - Mechanism of human chorionic gonadotrophin-mediated immunomodulation in
      pregnancy.
AB  - Human chorionic gonadotrophin (hCG) is released within hours of fertilization and
      has a profound ability to downregulate maternal cellular immunity against
      trophoblastic paternal antigens. It also promotes angiogenic activity of the
      extravillous trophoblast, and impairment of this function may lead to inadequate
      placentation and an increased risk of preeclampsia. There is increasing evidence
      that hCG alters the activity of dendritic cells via an upregulation of
      indoleamine 2,3-dioxygenase activity. This reduces T-cell activation and cytokine
      production, as well as encouraging Treg cell recruitment to the fetal-maternal
      interface. These changes are critical in promoting maternal tolerance. hCG is
      also able to increase the proliferation of uterine natural killer cells, while
      reducing the activity of cytotoxic peripheral blood natural killer cells. There
      are rare reports of autoantibodies directed against hCG or the luteinizing
      hormone/hCG receptor in women with recurrent miscarriage. These autoantibodies
      are more frequent in women with thyroid autoimmunity. This may explain the
      association between thyroid autoimmunity and impaired fertility. Downregulating
      these anti-hCG and anti-luteinizing hormone/hCG receptor autoantibodies may be
      helpful in some women with early miscarriage or recurrent failed in vitro
      fertilization.

PMID- 23167687
TI  - Occurrence, presentation and treatment of candidemia.
AB  - Candida is one of the most common causes of nosocomial bloodstream infections.
      Candidemia is not confined to hematological patients, intensive care units or
      abdominal surgery wards, but it is remarkably frequent in the internal medicine
      setting. High mortality associated with candidemia can be reduced by prompt,
      appropriate antifungal therapy. The epidemiology of species has been shifting
      toward non-albicans strains. Significant improvements in nonculture-based
      diagnostic methods, such as serological markers, have been made in recent years,
      and novel diagnostic techniques should be further studied to enable early pre
      emptive therapy. Treatment guidelines indicate that echinocandins are at present
      the best choice for patients who are severely ill or possibly infected with
      fluconazole-resistant strains.

PMID- 23167688
TI  - HIV-specific antibody-dependent cellular cytotoxicity: a novel vaccine modality.
AB  - A safe and effective HIV vaccine has eluded the scientific community for over
      three decades. With the failure of vaccines based on neutralizing antibody and
      cytotoxic T cells, researchers are seeking novel approaches. The partially
      successful RV144 vaccine trial focused scientific interest on binding antibodies,
      such as those that mediate antibody-dependent cellular cytotoxicity (ADCC). The
      biological importance of HIV-specific ADCC is strongly suggested by the
      generation of ADCC-escape HIV variants and passive transfer experiments. Newer
      assays for HIV-specific ADCC have defined new epitopes other than in the envelope
      protein. Such ADCC epitopes could be useful in novel HIV vaccine design.
      Researchers have shown that recombinant viral vectors such as canarypox or
      adenovirus boosted with recombinant HIV proteins can induce ADCC and lead to
      partial protection. These significant developments pave the way for trialing ADCC
      based technology in novel HIV vaccine studies.

PMID- 23167689
TI  - Natural killer cells in hepatitis C virus infection.
AB  - Hepatitis C virus (HCV) infection induces the long-term risk of liver cirrhosis
      or hepatocellular carcinoma and in adults represents the most common cause of
      liver transplantation. Natural killer (NK) cells participate in innate immune
      responses with efficient direct antitumor and antiviral defense. Over the years,
      their complex interaction with downstream adaptive responses and with the
      regulation of immune responses has been increasingly recognized. Considerable
      advances have been made particularly in understanding the role of NK cells in the
      pathophysiology of HCV infection and their possible use as biological markers for
      clinical purposes. This review summarizes the available data on the role of NK
      cells in the natural history of HCV infection and their role in the outcome of
      treatment. The main objective of this review is to summarize recent advancements
      in the basic understanding of NK cell function highlighting their possible
      translational use in clinical practice. An integrated practical view on the
      possible use of currently available predictive immunogenetic and NK cell
      functional tests is provided, to support clinical management choices for optimal
      treatment of patients with both standard and new drug regimens.

PMID- 23167691
TI  - Creation of an HDAC-based yeast screening method for evaluation of marine-derived
      actinomycetes: discovery of streptosetin A.
AB  - A histone deacetylase (HDAC)-based yeast assay employing a URA3 reporter gene was
      applied as a primary screen to evaluate a marine-derived actinomycete extract
      library and identify human class III HDAC (SIRT) inhibitors. On the basis of the
      bioassay-guided purification, a new compound designated as streptosetin A (1) was
      obtained from one of the active strains identified through the yeast assay. The
      gross structure of the new compound was elucidated from the 1D and 2D NMR data.
      The absolute stereostructure of 1 was determined based on X-ray crystal structure
      analysis and simulation of ECD spectra using time-dependent density functional
      theory calculations. This compound showed weak inhibitory activity against yeast
      Sir2p and human SIRT1 and SIRT2.

PMID- 23167692
TI  - Identification and characterization of the bacterial etiology of clinically
      problematic acute otitis media after tympanocentesis or spontaneous otorrhea in
      German children.
AB  - BACKGROUND: Acute Otitis Media (AOM) is an important and common disease of
      childhood. Bacteria isolated from cases of clinically problematic AOM in German
      children were identified and characterized. METHODS: In a prospective non
      interventional study in German children between 3 months and less than 60 months
      of age with Ear, Nose and Throat Specialist -confirmed AOM, middle ear fluid was
      obtained by tympanocentesis (when clinically indicated) or by careful sampling of
      otorrhea through/at an existing perforation. RESULTS: In 100 children with severe
      AOM, Haemophilus influenzae was identified in 21% (18/21, 85.7% were non-typeable
      [NTHi]), Streptococcus pneumoniae in 10%, S. pyogenes in 13% and Moraxella
      catarrhalis in 1%. H. influenzae was the most frequently identified pathogen in
      children from 12 months of age. H. influenzae and S. pneumoniae were equally
      prevalent in children aged 3-11 months, but S. pyogenes was most frequently
      isolated in this age group. NTHi AOM disease appeared prevalent in all ages.
      CONCLUSIONS: NTHi, S. pneumoniae and S. pyogenes are implicated as important
      causes of complicated AOM in children in Germany. NTHi disease appears prevalent
      in all ages. The impact of vaccination to prevent NTHi and S. pneumoniae AOM may
      be substantial in this population and is worth investigating.

PMID- 23167693
TI  - Nonlinear numerical analysis of the structural response of the intervertebral
      disc to impact loading.
AB  - The analysis of intervertebral disc dynamics under impact loading, using
      computational simulation, is scarcely reported. In this study, the contribution
      of the characteristic structure of the disc to its dynamic response has been
      evaluated. The influence of several model features on the dynamic response was
      investigated. A hyperelastic large deformation formulation was used to describe
      the nonlinear behaviour of the soft tissues. The material parameters were
      determined by the fitting of experimental data from the literature. The model
      demonstrated pressure wave propagation and reflection through the disc, with a
      periodic oscillation of the system in response to a single impulse load, and
      highlighted a potential primary role played by the collagen fibre reinforcement.
      Their tensioning contributes to changing the stress propagation and oscillation,
      with a faster reduction in the internal pressure peak. The natural frequency of
      the disc was predicted to be approximately 9.8 Hz for the vertical oscillation. 

PMID- 23167694
TI  - Nucleotide variants of genes encoding components of the Wnt signalling pathway
      and the risk of non-syndromic tooth agenesis.
AB  - Tooth agenesis is one of the most common dental anomalies, with a complex and not
      yet fully elucidated aetiology. Given the crucial role of the Wnt signalling
      pathway during tooth development, the purpose of this study was to determine
      whether nucleotide variants of genes encoding components of this signalling
      pathway might be associated with hypodontia and oligodontia in the Polish
      population. A set of 34 single nucleotide polymorphism (SNPs) in 13 WNT and WNT
      related genes were analyzed in a group of 157 patients with tooth agenesis and a
      properly matched control group (n = 430). In addition, direct sequencing was
      performed to detect mutations in the MSX1, PAX9 and WNT10A genes. Both single
      marker and haplotype analyses showed highly significant association between SNPs
      in the WNT10A gene and the risk for tooth agenesis. Moreover, nine pathogenic
      mutations within the coding region of the WNT10A gene were identified in 26 out
      of 42 (62%) tested patients. One novel heterozygous mutation was identified in
      the PAX9 gene. Borderline association with the risk of non-syndromic tooth
      agenesis was also observed for the APC, CTNNB1, DVL2 and WNT11 polymorphisms. In
      conclusion, nucleotide variants of genes encoding important components of the Wnt
      signalling pathway might influence the risk of tooth agenesis.

PMID- 23167695
TI  - Seasonal pasture myopathy/atypical myopathy in North America associated with
      ingestion of hypoglycin A within seeds of the box elder tree.
AB  - REASONS FOR PERFORMING STUDY: We hypothesised that seasonal pasture myopathy
      (SPM), which closely resembles atypical myopathy (AM), was caused by ingestion of
      a seed-bearing plant abundant in autumn pastures. OBJECTIVES: To identify a
      common seed-bearing plant among autumn pastures of horses with SPM, and to
      determine whether the toxic amino acid hypoglycin A was present in the seeds and
      whether hypoglycin metabolites were present in SPM horse serum or urine. METHODS:
      Twelve SPM cases, 11 SPM pastures and 23 control farms were visited to identify a
      plant common to all SPM farms in autumn. A common seed was analysed for amino
      acid composition (n = 7/7) by GC-MS and its toxic metabolite (n = 4/4) identified
      in conjugated form in serum [tandem mass spectrometry (MS/MS)] and urine [gas
      chromatography (GC) MS]. Serum acylcarnitines and urine organic acid profiles (n
      = 7) were determined for SPM horses. RESULTS: Seeds from box elder trees (Acer
      negundo) were present on all SPM and 61% of control pastures. Hypoglycin A, known
      to cause acquired multiple acyl-CoA dehydrogenase deficiency (MADD), was found in
      box elder seeds. Serum acylcarnitines and urine organic acid profiles in SPM
      horses were typical for MADD. The hypoglycin A metabolite
      methylenecyclopropylacetic acid (MCPA), known to be toxic in other species, was
      found in conjugated form in SPM horse serum and urine. Horses with SPM had longer
      turn-out, more overgrazed pastures, and less supplemental feeding than control
      horses. POTENTIAL RELEVANCE: For the first time, SPM has been linked to a toxin
      in seeds abundant on autumn pastures whose identified metabolite, MCPA, is known
      to cause acquired MADD, the pathological mechanism behind SPM and AM. Further
      research is required to determine the lethal dose of hypoglycin A in horses, as
      well as factors that affect annual seed burden and hypoglycin A content in Acer
      species in North America and Europe.

PMID- 23167696
TI  - Perinatal outcomes: intravenous patient-controlled fentanyl versus no analgesia
      in labor.
AB  - AIM: To investigate perinatal outcomes, the analgesic efficacy and maternal
      satisfaction in nulliparous women receiving fentanyl intravenous patient
      controlled analgesia (i.v.-PCA). MATERIAL AND METHODS: A total of 1401
      nulliparous women with a singleton pregnancy who received fentanyl i.v.-PCA (i.v.
      PCA group, n = 290) or no analgesia (control group, n = 1111) in labor between
      2005 and 2010 were reviewed. Fentanyl i.v.-PCA was implemented on maternal
      request during the first stage of labor over 35 weeks of gestation, and
      discontinued at full cervical dilatation. Perinatal outcomes were compared
      between the i.v.-PCA and the control groups. The numerical rating scale (NRS)
      levels during labor were also examined in the i.v.-PCA group. Additionally,
      parturients received fentanyl i.v.-PCA in 2010 (n = 73) were asked about overall
      satisfaction using a scale poor, moderate, good and excellent on postpartum day 0
      3. RESULTS: Women receiving i.v.-PCA showed significantly longer labor and more
      need of oxytocin augmentation, compared with the control. Cesarean section was
      significantly less frequent in the i.v.-PCA group compared with the control
      (11.0% v.s. 24.1%, respectively), with the vacuum-assisted delivery rate
      comparable between groups. Neonatal outcomes (i.e. Apgar score <7 at 1 min or 5
      min, umbilical artery pH <7.20) were comparable between groups, irrespective of
      mode of delivery. Significant reduction of NRS levels was noted until 3 h after
      induction of i.v.-PCA, compared to the baseline. Of the women who expressed their
      satisfaction, 72% (48/67) exhibited 'excellent' or 'good' for pain relief by i.v.
      PCA. CONCLUSION: Fentanyl i.v.-PCA could be a useful approach for labor pain
      relief in nulliparas when regional blocks are unavailable.

PMID- 23167697
TI  - A hierarchy in reprogramming capacity in different tissue microenvironments: what
      we know and what we need to know.
AB  - Ectopic expression of certain transcription factors induces reprogramming of
      somatic cells to a pluripotent state. A number of studies have shed light on the
      reprogramming capacity of various cell populations. As a result, it has been
      shown that stem/progenitor cells derived from organs of all germ layers exhibit a
      superior reprogramming efficiency compared to their differentiated progeny.
      Although proliferative capacity and endogenous expression levels of pluripotency
      factors are likely to be involved in this superiority, the detailed molecular
      understanding remains elusive so far. Recently, we have shown that the BAF
      complex (BAF155 and Brg1), mediating epigenetic changes during reprogramming, is
      critical for the increased reprogramming efficiency of liver progenitor cells. In
      this review, we summarize recently acquired findings of the increased
      reprogramming capacity of adult stem/progenitor cell populations compared to
      their differentiated counterparts and discuss the potential mechanisms involved.

PMID- 23167698
TI  - The pharmacokinetics of maropitant citrate dosed orally to dogs at 2 mg/kg and 8
      mg/kg once daily for 14 days consecutive days.
AB  - The pharmacokinetics of maropitant were evaluated in beagle dogs dosed orally
      with Cerenia(r) tablets (Pfizer Animal Health) once daily for 14 consecutive days
      at either 2 mg/kg or 8 mg/kg bodyweight. Noncompartmental pharmacokinetic
      analysis was performed on the plasma concentration data to measure the AUC(0-24)
      (after first and last doses), Ct (trough concentration-measured 24 h after each
      dose), Cmax (after first and last doses), tmax (after first and last doses),
      lambdaz (terminal disposition rate constant; after last dose), t(1/2) (after last
      dose), and CL/F (oral clearance; after last dose). Maropitant accumulation in
      plasma was substantially greater after fourteen daily 8 mg/kg doses than after
      fourteen daily 2 mg/kg doses as reflected in the AUC(0-24) accumulation ratio of
      4.81 at 8 mg/kg and 2.46 at 2 mg/kg. This is most likely due to previously
      identified nonlinear pharmacokinetics of maropitant in which high doses (8 mg/kg)
      saturate the metabolic clearance mechanisms and delay drug elimination. To
      determine the time to reach steady-state maropitant plasma levels, a nonlinear
      model was fit to the least squares (LS) means maropitant Ct values for each
      treatment group. Based on this model, 90% of steady-state was determined to occur
      at approximately four doses for daily 2 mg/kg oral dosing and eight doses for
      daily 8 mg/kg oral dosing.

PMID- 23167699
TI  - Meta-synthesis and evidence-based health care--a method for systematic review.
AB  - BACKGROUND: Even the systematic reviews of qualitative studies are discussed
      health literature, the significance of their results is not fully recognised in
      evidence-based practice. AIM: The aim of this article is to describe the
      systematic reviews of qualitative studies, metasynthesis and its process and
      consider the meaning of meta-synthesis in evidence-based practice. CONCLUSIONS:
      Meta-synthesis is a method for synthesising knowledge, for example, relating to
      service users' healthcare-related experiences and the factors that facilitate
      their involvement in their own care and commitment to a healthy lifestyle. This
      type of knowledge is needed in evidence-based practice. Meta-synthesis is a
      concept that includes several methodologies in synthesising qualitative research
      findings. This article focuses on meta-synthesis with meta-aggregation as a
      method for combining data from original studies. Following the principles of
      scientific rigour, systematic reviews synthesise the best available and
      critically appraised knowledge. The article describes the process and the role of
      systematic review of qualitative studies and discusses its significance for
      evidence-based practice when making clinical and administrative decisions, as
      well as more widely in social and political decision-making.

PMID- 23167700
TI  - Validity of anthropometric measurements to assess body composition, including
      muscle mass, in 3-year-old children from the SKOT cohort.
AB  - Nutritional status of children is commonly assessed by anthropometry both in
      under and overnutrition. The link between anthropometry and body fat, the body
      compartment most affected by overnutrition, is well known, but the link with
      muscle mass, the body compartment most depleted in undernutrition, associated
      with infections, remains unknown. In this study, we examined the relationship
      between common anthropometric indices and body composition measured by dual
      energy X-ray absorptiometry (DEXA) in a sample of 121 healthy 3-year-old Danish
      children. Appendicular (arms and legs) lean mass was used to estimate muscle
      mass. Overall, anthropometric measures were more effective to measure absolute
      size of fat, lean and muscle mass than their relative sizes. Proportion of the
      variance explained by anthropometry was 79% for lean mass, 76% for fat mass and
      74% for muscle mass. For fat mass and lean mass expressed as percentage of total
      body mass, this proportion was 51% and 66%, respectively; and for muscle mass as
      percentage of lean mass it was 34%. All the best reduced multivariate models
      included weight, skinfold and gender except the model estimating the proportion
      of muscle mass in lean body mass, which included only mid-upper arm circumference
      and subscapular skinfold. The power of height in the weight-to-height ratio to
      determine fat mass proportion was 1.71 with a 95% confidence interval (0.83-2.60)
      including the value of 2 used in body mass index (BMI). Limitations of
      anthropometry to assess body composition, and especially for muscle mass as a
      proportion of lean mass, should be acknowledged. 

PMID- 23167701
TI  - Assessment of factors influencing retention in the Philippine National Rural
      Physician Deployment Program.
AB  - BACKGROUND: The 'Doctors to the Barrios' (DTTB) Program was launched in 1993 in
      response to the shortage of doctors in remote communities in the Philippines.
      While the Program has attracted physicians to work in such areas for the
      prescribed 2-year period, ongoing monitoring shows that very few chose to remain
      there for longer and be absorbed by their Local Government Unit (LGU). This
      assessment was carried out to explore the reasons for the low retention rates and
      to propose possible strategies to reverse the trend. METHODS: A mixed methods
      approach was used comprising a self-administered questionnaire for members of the
      current cohort of DTTBs, and oral interviews with former DTTBs. RESULTS: Among
      former DTTBs, the wish to serve rural populations was the most widely cited
      motivation. By comparison, among the current cohort of DTTBs, more than half
      joined the Program due to return of service obligations; a quarter to help rural
      populations, and some out of an interest in public health. Those who joined the
      Program to return service experienced significantly less satisfaction, whilst
      those who joined out of an interest in public health were significantly more
      satisfied with their rural work. Those who graduated from medical schools in the
      National Capital Region were significantly more critical about their compensation
      and perceived there to be fewer options for leisure in rural areas. With regard
      to the factors impeding retention, lack of support from the LGU was most
      frequently mentioned, followed by concerns about changes in compensation upon
      absorption by the LGU, family issues and career advancement. CONCLUSIONS: Through
      improved collaboration with the Department of Health, LGUs need to strengthen the
      support provided to DTTBs. Priority could be given to those acting out of a
      desire to help rural populations or having an interest in public health, and
      those who have trained outside of the National Capital Region. Whether physicians
      should be able to use the Program to fulfil return service obligations should be
      critically assessed.

PMID- 23167702
TI  - Eu(2+)-activated Sr8ZnSc(PO4)7: a novel near-ultraviolet converting yellow
      emitting phosphor for white light-emitting diodes.
AB  - The crystal structure of Eu(2+)-activated Sr(8)ZnSc(PO(4))(7):Eu(2+) phosphor was
      refined and determined from XRD profiles by the Rietveld refinement method using
      a synchrotron light source. This phosphor crystallizes in the monoclinic
      structure with the I2/a space group. The SZSP:xEu(2+) phosphors showed a broad
      yellow emission band centered at 511 and 571 nm depending on the concentration of
      Eu(2+), and the composition-optimized concentration of Eu(2+) in the
      Sr(8)ZnSc(PO(4))(7):Eu(2+) phosphor was determined to be 2 mol %. The estimated
      crystal-field splitting and CIE chromaticity coordinates of
      Sr(8)ZnSc(PO(4))(7):xEu(2+) (x = 0.001-0.05 mol) were 20181-20983 cm(-1) and
      (0.3835, 0.5074) to (0.4221, 0.5012), respectively, and the emission band showed
      a redshift from 547 to 571 nm with increasing Eu(2+) concentration. The
      nonradiative transitions between the Eu(2+) ions in the Sr(8)ZnSc(PO(4))(7) host
      were attributable to dipole-dipole interactions, and the critical distance was
      approximately 19.8 A. The combination of a 400 nm NUV chip with a blend of
      Sr(8)ZnSc(PO(4))(7):0.02Eu(2+) and BAM:Eu(2+) phosphors (light converters) gave
      high color rendering indices between 79.38 and 92.88, correlated color
      temperatures between 4325 and 7937 K, and tuned CIE chromaticity coordinates in
      the range (0.381, 0.435) to (0.294, 0.310), respectively, depending on the
      SZSP:0.02Eu(2+)/BAM:Eu(2+) weight ratio. These results suggest that the
      Sr(8)ZnSc(PO(4))(7):0.02Eu(2+)/BAM:Eu(2+) phosphor blend has potential
      applications in white NUV LEDs.

PMID- 23167703
TI  - Urinary L-FABP and its combination with urinary NGAL in early diagnosis of acute
      kidney injury after cardiac surgery in adult patients.
AB  - BACKGROUND/AIM: The early detection of acute kidney injury (AKI) may be become
      possible by several promising early biomarkers which may facilitate the early
      detection, differentiation and prognosis prediction of AKI. In this study, we
      investigated the value of urinary liver-type fatty acid-binding protein (L-FABP),
      neutrophil gelatinase-associated lipocalin (NGAL) and their combination in
      predicting the occurrence and the severity of AKI following cardiac surgery.
      METHODS: We prospectively followed 109 patients undergoing open heart surgery and
      identified 26 that developed AKI, defined as an increase in serum creatinine of
      >=0.3 mg/dl or >=150% of baseline creatinine. Serum creatinine (SCr), urinary L
      FABP, and NGAL corrected by urine creatinine were tested pre-operation, at 0 hour
      and 2 hours post-operation. Each marker was assessed at each time point between
      patients with and without AKI. Receiver operating characteristic (ROC) curves and
      area under curves (AUC) were used to evaluate the diagnostic accuracy of urinary
      L-FABP, NGAL and their combination for predicting AKI. RESULTS: Patients were
      aged 63.0 +/- 11.3 years, 66.1% were male and baseline SCr was 70.5 +/- 19.1
      umol/L. Of 109 patients, 26(23.9%) developed AKI (AKIN stage I, II and III were
      46.2%, 34.6% and 19.2% separately). The levels of urinary L-FABP and NGAL were
      significantly higher in AKI patients than non-AKI patients at 0 hour and 2 hours
      postoperative. AUCs for L-FABP was 0.844 (sensitivity (ST) 0.846, specificity
      (SP) 0.819, cut-off (CO) 2226.50 MUg/g Ucr) at 0 hours and 0.832 at 2 hours (ST
      0.808, SP 0.747, CO 673.09 MUg/g Ucr) while 0.866 for NGAL at 0 hours (ST 0.769,
      SP 0.819, CO 131.12 MUg/g Ucr) and 0.871 at 2 hours (ST 0.808, SP 0.831, CO 33.73
      MUg/g Ucr) to predict AKI occurrence. Using a combination of L-FABP and NGAL
      analyzed at the same timepoint as above, we were able to obtain an AUC of 0.911
      0.927, p < 0.001. Similar AUCs of 0.81-0.87 were found to predict AKI stage II
      III. CONCLUSIONS: Urinary L-FABP and NGAL increased at an early stage after
      cardiac surgery. The combination of the two biomarkers enhanced the accuracy of
      the early detection of postoperative AKI after cardiac surgery before a rise in
      SCr.

PMID- 23167704
TI  - Is Trichophyton simii endemic to the Indian subcontinent?
AB  - Trichophyton simii is considered to be prevalent only in the Indian subcontinent
      where it was isolated from soil, as well as from infections of humans and
      animals. We have investigated a case of onychomycosis caused by this exotic
      dermatophyte, not traceable to endemic areas. This case, as in others due to this
      fungus in man or animals, that have been previously and sporadically reported
      worldwide, suggests infections caused by T. simii might be underestimated,
      especially outside its primary geographic areas. Indeed, there are isolates that
      do not show species-specific morphology, as in our case isolate, and as a result
      may be misidentified by classical methods. By checking the identity of some
      strains preserved in the collection BCCM/IHEM, we found several that proved to be
      T. simii, originating from non-endemic areas (Belgium, France and Ivory Coast).
      Therefore, the natural distribution of T. simii is probably not as restricted as
      has previously been proposed.

PMID- 23167705
TI  - Genetic diversity of Coccidioides posadasii from Brazil.
AB  - Studies of the genetic variation within populations of Coccidioides posadasii are
      scarce, especially for those recovered from South America. Understanding the
      distribution of genotypes among populations is important for epidemiological
      surveillance. This study evaluated the genetic diversity of 18 Brazilian strains
      of C. posadasii through the sequencing of the 18-28S region of nuclear rDNA, as
      well as through RAPD and M13-PCR fingerprinting techniques. The sequences
      obtained were compared to Coccidioides spp. previously deposited in GenBank. The
      MEGA5 program was used to perform phylogenetic analyses. Within the C. posadasii
      clade, a single cluster was observed, containing seven isolates from Ceara, which
      presented a single nucleotide polymorphism. These isolates were from the same
      geographical area. The strains of C. posadasii showed a lower rate of genetic
      diversity in the ITS1 and ITS2 regions. The results of M13 and RAPD-PCR
      fingerprinting indicated a similar electrophoretic profile. No differences
      between clinical and environmental isolates were detected. This was the first
      study assessing the genetic variability of a larger number of C. posadasii
      isolates from Brazil.

PMID- 23167706
TI  - Molecular analysis of Malassezia pachydermatis isolated from canine skin and ear
      in Korea.
AB  - We investigated Malassezia species and genotypes colonizing dogs, comparing those
      recovered from the ear canal with those from other anatomical body sites, as well
      as from diseased and healthy skin. The Malassezia isolates were obtained from
      four types of skin samples, i.e., diseased ear, diseased skin, healthy ear, and
      healthy skin. Sequences of the 26S ribosomal DNA region, the intergenic spacer 1
      (IGS-1) and the internal transcribed spacer 1 (ITS-1) DNA region were analyzed.
      These confirmed the presence of Malassezia pachydermatis, which could be
      separated into three main sequence genotype groups (A, B, C). Genotype A was the
      most common, only two genotype B isolates were recovered from diseased skin
      lesion and genotype C was more likely to be isolated from ear samples than from
      other healthy or diseased-skin sites. The present findings provide the basis for
      further studies of genotypic diversity in M. pachydermatis, as well as their
      pathogenic potential.

PMID- 23167707
TI  - Dishwashers are a major source of human opportunistic yeast-like fungi in indoor
      environments in Mersin, Turkey.
AB  - The natural habitat of opportunistic fungal pathogens is outside of the host;
      therefore, it is crucial to understand their ecology and routes of transmission.
      In this study, we investigated the presence of black and filamentous fungi in
      moist indoor environments in the city of Mersin in subtropical Turkey. In total,
      177 private dwellings were screened and 893 samples obtained using cotton swabs
      and moistened with physiological saline from dishwashers, washing machines,
      refrigerators, bath-tubs, bathroom walls, and shower heads. These were then
      inoculated onto malt extract agar supplemented with chloramphenicol, followed by
      incubation at 37 degrees C. Thirty samples (3.4%) were positive for fungi, which
      were then identified by sequencing the rDNA internal transcribed spacer region.
      Exophiala dermatitidis was the most common species (23), followed by E.
      phaeomuriformis (three), Magnusiomyces capitatus (two), and Candida parapsilosis
      (two). Genotype A of E. dermatitidis (14) was more prevalent than genotypes B
      (eight) and C (one) and E. phaeomuriformis was also represented by two genotypes.
      Our findings suggest that dishwashers are a major indoor niche for thermophilic
      black yeasts. The occurrence of the opportunistic filamentous fungus M. capitatus
      in dishwashers is consistent with a recent report.

PMID- 23167708
TI  - A trifluoroacetic acid-labile sulfonate protecting group and its use in the
      synthesis of a near-IR fluorophore.
AB  - Sulfonated molecules exhibit high water solubility, a property that is valuable
      for many biological applications but often complicates their synthesis and
      purification. Here we report a sulfonate protecting group that is resistant to
      nucleophilic attack but readily removed with trifluoroacetic acid (TFA). The use
      of this protecting group improved the synthesis of a sulfonated near-IR
      fluorophore and the mild deprotection conditions allowed isolation of the product
      without requiring chromatography.

PMID- 23167709
TI  - Quantitative current-voltage characteristics in molecular junctions from first
      principles.
AB  - Using self-energy-corrected density functional theory (DFT) and a coherent
      scattering-state approach, we explain current-voltage (IV) measurements of four
      pyridine-Au and amine-Au linked molecular junctions with quantitative accuracy.
      Parameter-free many-electron self-energy corrections to DFT Kohn-Sham eigenvalues
      are demonstrated to lead to excellent agreement with experiments at finite bias,
      improving upon order-of-magnitude errors in currents obtained with standard DFT
      approaches. We further propose an approximate route for prediction of
      quantitative IV characteristics for both symmetric and asymmetric molecular
      junctions based on linear response theory and knowledge of the Stark shifts of
      junction resonance energies. Our work demonstrates that a quantitative,
      computationally inexpensive description of coherent transport in molecular
      junctions is readily achievable, enabling new understanding and control of charge
      transport properties of molecular-scale interfaces at large bias voltages.

PMID- 23167710
TI  - Detection of multiple waterborne pathogens using microsequencing arrays.
AB  - AIMS: A microarray was developed to simultaneously detect Cryptosporidium parvum,
      Cryptosporidium hominis, Enterococcus faecium, Bacillus anthracis and Francisella
      tularensis in water. METHODS AND RESULTS: A DNA microarray was designed to
      contain probes that specifically detected C. parvum, C. hominis, Ent. faecium, B.
      anthracis and F. tularensis. The microarray was then evaluated with samples
      containing target and nontarget DNA from near-neighbour micro-organisms, and tap
      water spiked with multiple organisms. Results demonstrated that the microarray
      consistently detected Ent. faecium, B. anthracis, F. tularensis and C. parvum
      when present in samples. Cryptosporidium hominis was only consistently detected
      through the use of shared probes between C. hominis and C. parvum. CONCLUSIONS:
      This study successfully developed and tested a microarray-based assay that can
      specifically detect faecal indicator bacteria and human pathogens in tap water.
      SIGNIFICANCE AND IMPACT OF THE STUDY: The use of indicator organisms has become a
      practical solution for monitoring for water quality. However, they do not always
      correlate well with the presence of many microbial pathogens, thus necessitating
      direct monitoring for most pathogens. This microarray can be used to
      simultaneously detect multiple organisms in a single sample. More importantly, it
      can provide occurrence information that may be used in assessing potential
      exposure risks to waterborne pathogens.

PMID- 23167711
TI  - The D2/3 dopamine receptor in pathological gambling: a positron emission
      tomography study with [11C]-(+)-propyl-hexahydro-naphtho-oxazin and
      [11C]raclopride.
AB  - AIMS: Pathological gambling (PG) shares diagnostic features with substance use
      disorder (SUD), but the neurochemical mechanisms underlying PG are poorly
      understood. Because dopamine (DA), a neurotransmitter implicated in reward and
      reinforcement, is probably involved, we used positron emission tomography (PET)
      to test whether PG is associated with abnormalities in D2 and D3 receptor levels,
      as observed in SUD. DESIGN: Case-control study comparing PG to healthy control
      (HC) subjects. SETTING: Academic research imaging centre. PARTICIPANTS: Thirteen
      non-treatment-seeking males meeting DSM-IV criteria for PG, and 12 matched HC (11
      of whom completed PET). MEASUREMENTS: Two PET scans (one with the D3 receptor
      preferring agonist [11C]-(+)-propyl-hexahydro-naphtho-oxazin (PHNO) and the other
      with [11C]raclopride) to assess D(2/3) DA receptor availability, and behavioural
      measures (self-report questionnaires and slot-machine game) to assess subjective
      effects and relationships to PET measures. FINDINGS: Binding of both radiotracers
      did not differ between groups in striatum or substantia nigra (SN) (all P > 0.1).
      Across PG, [11C]-(+)-PHNO binding in SN, where the signal is attributable
      primarily to D3 receptors, correlated with gambling severity (r = 0.57, P = 0.04)
      and impulsiveness (r = 0.65, P = 0.03). In HC, [11C]raclopride binding in dorsal
      striatum correlated inversely with subjective effects of gambling (r = -0.70, P =
      0.03) and impulsiveness (r = -0.70, P = 0.03). CONCLUSIONS: Unlike with substance
      use disorder, there appear to be no marked differences in D2 /D3 levels between
      healthy subjects and pathological gamblers, suggesting that low receptor
      availability may not be a necessary feature of addiction. However, relationships
      between [11C]-(+)-PHNO binding and gambling severity/impulsiveness suggests
      involvement of the D3 receptor in impulsive/compulsive behaviours.

PMID- 23167712
TI  - Affect-specific modulation of the N1m to shock-conditioned tones:
      magnetoencephalographic correlates.
AB  - Despite its fundamental relevance for representing the emotional world
      surrounding us, human affective neuroscience research has widely neglected the
      auditory system, at least in comparison to the visual domain. Here, we have
      investigated the spatiotemporal dynamics of human affective auditory processing
      using time-sensitive whole-head magnetoencephalography. A novel and highly
      challenging affective associative learning procedure, 'MultiCS conditioning',
      involving multiple conditioned stimuli (CS) per affective category, was adopted
      to test whether previous findings from intramodal conditioning of multiple click
      tones with an equal number of auditory emotional scenes (Brockelmann et al., 2011
      J. Neurosci., 31, 7801) would generalise to crossmodal conditioning of multiple
      click-tones with an electric shock as single aversive somatosensory unconditioned
      stimulus (UCS). Event-related magnetic fields were recorded in response to 40
      click-tones before and after four contingent pairings of 20 CS with a shock and
      the other half remaining unpaired. In line with previous findings from intramodal
      MultiCS conditioning we found an affect-specific modulation of the auditory N1m
      component 100-150 ms post-stimulus within a distributed frontal-temporal-parietal
      neural network. Increased activation for shock-associated tones was lateralised
      to right-hemispheric regions, whereas unpaired safety-signalling tones were
      preferentially processed in the left hemisphere. Participants did not show
      explicit awareness of the contingent CS-UCS relationship, yet behavioural
      conditioning effects were indicated on an indirect measure of stimulus valence.
      Our findings imply converging evidence for a rapid and highly differentiating
      affect-specific modulation of the auditory N1m after intramodal as well
      crossmodal MultiCS conditioning and a correspondence of the modulating impact of
      emotional attention on early affective processing in vision and audition.

PMID- 23167713
TI  - Images in cardiovascular medicine: caseous calcification of the mitral annulus.
AB  - A 78-year-old woman was admitted to our emergency department for subarachnoid
      hemorrhage. Since a month ago, she was taking warfarin after diagnosis, on
      transthoracic echocardiogram (TTE), of a suspected large atrial thrombus. The
      patient, referred to our institution for further investigation, presented
      asymptomatic; electrocardiogram showed sinus rhythm. TTE revealed an echo dense
      spherical mass located in the mitral periannular posterior region with moderate
      mitral regurgitation. Transesophageal echocardiography and cardiac computed
      tomography confirmed a calcified round mass (2.0 * 2.9 cm) with central areas of
      echolucency-like liquefaction surrounded by a hyperechogenic structure without
      systolic flow inside the cavity. The mass was diagnosed as caseous calcification
      of the mitral annulus (CCMA), a rare finding associated with a benign prognosis,
      requiring surgery only in the presence of mitral valve dysfunction. The diagnosis
      of CCMA is, often, misconstrued as thrombus, tumor, or abscess, leading to
      unnecessary investigations or interventions. Our patient was discharged after
      discontinuation of warfarin.

PMID- 23167714
TI  - Nutritional antioxidants and their applications in cardiometabolic diseases.
AB  - There is an increasing global trend in cardiometabolic disorders being a leading
      cause of morbidity and mortality. Adverse dietary habits and sedentary lifestyles
      contribute to cardiovascular disease (CVD) and diabetes mellitus (DM). Dietary
      nutrients in nuts have attracted attention in recent literature due to their
      beneficial effects on CVD by attenuating lipid profiles, inflammation and
      oxidative stress. There is well-established evidence of the pharmacological
      properties of micronutrients that render them therapeutically effective in
      chronic inflammatory diseases. Although caution should be exercised in using
      antioxidant supplementation, antioxidant foods as dietary components play an
      important role in the management of cardiometabolic disorders. There is
      documented evidence of disease-modifying effects of nutritional compounds with
      anti-inflammatory and antioxidant effects. They have specific applications in
      ameliorating oxidative stress- induced inflammatory diseases such as DM and CVD.
      It is relevant that dietary components that influence risk of DM, have similar
      effects on inflammatory biomarkers of cardiovascular risk. Polyphenolic compounds
      such as flavonoids, isoflavones, phenolic acids and lignan contribute to
      increased plasma antioxidant capacity, decreased oxidative stress markers and
      reduced total and LDL cholesterol. They modulate genes associated with
      metabolism, stress defence, detoxification and transporter proteins. Their
      antioxidant and anti-inflammatory actions have specific applications for
      pathologies associated with chronic low-grade systemic inflammation that
      underpins progression of DM and CVD. Mechanisms involved depend on the structure
      of the compound, redox status of the inflammatory milieu and other interactions.
      Bioactive phytochemicals play an important therapeutic role in attenuating
      oxidative damage induced by metabolic syndrome associated with atherogenic
      dyslipidaemia and a pro-inflammatory, pro-thrombotic state, at a sub-cellular
      level. It would be critical to formulate optimal proportions and their
      combinations for therapeutic efficacy, based on synergistic interactions. Some of
      these mechanisms and potential actions are discussed.

PMID- 23167716
TI  - Biomimetic catalysis of a porous iron-based metal-metalloporphyrin framework.
AB  - A porous metal-metalloporphyrin framework, MMPF-6, based upon an iron(III)
      metalated porphyrin ligand and a secondary binding unit of a zirconium oxide
      cluster was constructed; MMPF-6 demonstrated interesting peroxidase activity
      comparable to that of the heme protein myoglobin as well as exhibited solvent
      adaptability of retaining the peroxidase activity in an organic solvent.

PMID- 23167717
TI  - The CAG repeat polymorphism in the androgen receptor gene modifies the risk for
      hypospadias in Caucasians.
AB  - BACKGROUND: Hypospadias is a birth defect of the urethra in males, and a milder
      form of 46,XY disorder of sexual development (DSD). The disease is characterized
      by a ventrally placed urinary opening due to a premature fetal arrest of the
      urethra development. Moreover, the Androgen receptor (AR) gene has an essential
      role in the hormone-dependent stage of sexual development. In addition, longer AR
      polyglutamine repeat lengths encoded by CAG repeats are associated with lower
      transcriptional activity in vitro. In the present study, we aimed at
      investigating the role of the CAG repeat length in the AR gene in hypospadias
      cases as compared to the controls. Our study included 211 hypospadias and 208
      controls of Caucasian origin. METHODS: We amplified the CAG repeat region with
      PCR, and calculated the difference in the mean CAG repeat length between the
      hypospadias and control group using the T-test for independent groups. RESULTS:
      We detected a significant increase of the CAG repeat length in the hypospadias
      cases when compared to the controls (contrast estimate: 2.29, 95% Confidence
      Interval (1.73-2.84); p-value: 0.001). In addition, the odds ratios between the
      hypospadias and controls revealed that the hypospadias cases are two to 3 times
      as likely to have longer CAG repeats than a shorter length for each repeat length
      investigated. CONCLUSIONS: We have investigated the largest number of hypospadias
      cases with regards to the CAG repeat length, and we provide evidence that a
      higher number of the CAG repeat sequence in the AR gene have a clear effect on
      the risk of hypospadias in Caucasians.

PMID- 23167718
TI  - Oxytocin versus sustained-release dinoprostone vaginal pessary for labor
      induction of unfavorable cervix with Bishop score >= 4 and <= 6: a randomized
      controlled trial.
AB  - AIM: To compare the efficacy and safety of high-dose intravenous oxytocin and
      sustained-release dinoprostone vaginal pessaries for cervical ripening and labor
      induction in pregnant patients at term with poor Bishop scores. MATERIAL AND
      METHODS: Women at term with a Bishop score >= 4 and <= 6 were randomized into two
      groups to undergo induction of labor with either high-dose oxytocin administered
      intravenously (n = 90) or dinoprostone-only vaginal pessary without oxytocin
      augmentation (n = 90). The main outcome measures were rate of cesarean delivery,
      induction to delivery interval, number of deliveries achieved within 4, 8, 12,
      and 16 h of labor induction, maternal complications during induction, fetal
      outcome, and total hospital stay. In this study, per-protocol analysis was
      performed. RESULTS: There were fewer cesarean deliveries with oxytocin compared
      to dinoprostone-only groups (7/79 vs 14/89); however, the difference was not
      statistically significant. The induction-delivery intervals (7.9 h vs 12.0 h, P <
      0.001; and 5.7 vs 10.4 h, P < 0.001; oxytocin vs dinoprostone-only for
      primiparous and multiparous patients, respectively) were significantly shorter in
      oxytocin-induced patients compared to dinoprostone-only. A significantly higher
      percentage of patients delivered in the oxytocin group compared to the
      dinoprostone-only group in 4, 8, 12, 16, and 20 h. CONCLUSION: Intravenous
      oxytocin is effective to stimulate labor at term for patients with Bishop scores
      >= 4 and <= 6, with a shorter time interval from induction to vaginal delivery.

PMID- 23167720
TI  - New flavan-3-ol dimer from green tea produced from Camellia taliensis in the Ai
      Lao mountains of Southwest China.
AB  - Camellia taliensis (W. W. Smith) Melchior, belonging to the genus Camellia sect.
      Thea (Theaceae), is an endemic species distributed from the west and southwest of
      Yunnan province, China, to the north of Myanmar. Known as a wild tea tree, its
      leaves have been used commonly for producing tea beverages by the local people of
      its growing area. One new flavan-3-ol dimer, talienbisflavan A (1), was isolated
      from green tea prepared from the leaves of C. taliensis collected from the east
      side of the Ai-Lao mountains, Yuanjiang county of Yunnan province, China. In
      addition, five hydrolyzable tannins (2-6), five flavonols and flavonol glycosides
      (9-13), three flavan-3-ols (14-16), nine simple phenolic compounds and glycosides
      (7, 8, and 17-23), and caffeine (24) were identified. Their structures were
      determined by detailed spectroscopic analysis. All of the isolated phenolic
      compounds were tested for their antioxidant activities by DPPH and ABTS(+)
      radical scavenging assays. The contents of its main chemical compositions were
      also compared with those collected from the Lincang area of Yunnan province by
      high-performance liquid chromatography analysis.

PMID- 23167715
TI  - Withdrawn
AB  - Withdrawn by the publisher.

PMID- 23167721
TI  - Predictors and outcomes of nurse leader job stress experienced by AWHONN members.
AB  - OBJECTIVE: To measure the relationships among stressors (personal factors,
      job/role factors, hospital factors), job stress, and outcomes experienced by
      nurse leaders and examine moderation of autonomy and leadership style on outcomes
      of job stress. DESIGN: A cross-sectional, quantitative design. SETTING: Acute and
      nonacute care settings throughout North America. PARTICIPANTS: A nonprobability
      convenience sample of 392 was drawn from a population of nurse leaders across the
      United States and Canada who were members of the Association of Women's Health,
      Obstetric and Neonatal Nurses (AWHONN). METHODS: A mailing list was obtained from
      AWHONN, and a total of 3,986 recruitment and follow-up postcards were sent to
      nurse leaders. Participants were asked to complete the survey online or request a
      hard copy to return by mail. Study variables were measured using previously
      published scales with demonstrated psychometric properties. RESULTS: Nurse
      leaders reported stress averages above the midpoint of the scales. Personal
      factors did not significantly predict stress, but role overload, organizational
      constraints, and role ambiguity were found to be the best predictors of stress.
      Job satisfaction, intent to quit, and mental health symptoms were the most
      significant outcomes of stress. Autonomy moderated relationships between
      perceptions of stress and outcomes with low autonomy showing greater negative
      outcomes when levels of stress are higher. CONCLUSION: Nurse leaders experience
      significant job stress that may suggest a need to design and implement evidence
      based interventions to reduce stress among this group.

PMID- 23167722
TI  - Deviations between placed and planned implant positions: an accuracy pilot study
      of skeletally supported stereolithographic surgical templates.
AB  - PURPOSE: The aim of the present study was to evaluate deviations between
      virtually planned and placed implants by the use of skeletally supported
      stereolithographic templates. MATERIALS AND METHODS: Ten consecutive patients
      were selected for virtual three-dimensional implant planning using the
      Facilitate(TM) software (Astra Tech AB, Molndal, Sweden). Computer tomography
      images were obtained in the pre- and postoperative phase. Four deviation
      parameters (i.e. global, angular, depth, and lateral deviation) were defined and
      calculated between the planned and the placed implants, using the coordinates of
      their respective apical and coronal points. RESULTS: Deviations at the coronal
      positions appeared to be smaller (95% confidence interval: 0.15-1.0) as compared
      with apical positions (95% confidence interval: 0.14-1.1). But only the
      difference with regard to lateral measurements appeared to be statistically
      significant (p = .03). Except for depth (p = .01), no significant association
      between mesial or more distal locations could be detected concerning global (p =
      .07), lateral (p = .87), and angular (p = .56) values in mixed model analyses.
      Overall, there was a slight tendency for higher values for more distal locations.
      CONCLUSION: As slight deviations between planned and placed implants especially
      may occur even with skeletal-supported templates, the clinician should be aware
      not to overestimate advocated surgical safety by using static navigation tools.

PMID- 23167723
TI  - Force and torque modelling of drilling simulation for orthopaedic surgery.
AB  - The advent of haptic simulation systems for orthopaedic surgery procedures has
      provided surgeons with an excellent tool for training and preoperative planning
      purposes. This is especially true for procedures involving the drilling of bone,
      which require a great amount of adroitness and experience due to difficulties
      arising from vibration and drill bit breakage. One of the potential difficulties
      with the drilling of bone is the lack of consistent material evacuation from the
      drill's flutes as the material tends to clog. This clogging leads to significant
      increases in force and torque experienced by the surgeon. Clogging was observed
      for feed rates greater than 0.5 mm/s and spindle speeds less than 2500 rpm. The
      drilling simulation systems that have been created to date do not address the
      issue of drill flute clogging. This paper presents force and torque prediction
      models that account for this phenomenon. The two coefficients of friction
      required by these models were determined via a set of calibration experiments.
      The accuracy of both models was evaluated by an additional set of validation
      experiments resulting in average R2 regression correlation values of 0.9546 and
      0.9209 for the force and torque prediction models, respectively. The resulting
      models can be adopted by haptic simulation systems to provide a more realistic
      tactile output.

PMID- 23167724
TI  - Aging in Rett syndrome: a longitudinal study.
AB  - Little is known about the aging process of people with specific syndromes, like
      Rett syndrome (RTT). Recognition of the clinical and behavioral characteristics
      of the adult RTT is needed in order to improve future management of the RTT girl
      and counseling of parents. In association with the Dutch RTT parent association,
      a 5-year longitudinal study was carried out. The study population consisted of 53
      adult women with a clinical diagnosis of RTT. Postal questionnaires were sent,
      including demographic features, skills, physical and psychiatric morbidity. At
      the time of the second measurement seven women had died. In 2012, 80% of the
      questionnaires (37/46) were returned. Mean age of the women was 31.4 years.
      Molecular confirmation was possible for 83% of the women for whom analyses were
      carried out. The adult RTT woman has a more or less stable condition. The general
      disorder profile is that of a slow on-going deterioration of gross motor
      functioning in contrast to a better preserved cognitive functioning, less
      autonomic and epileptic features and good general health. This is the first
      longitudinal cohort study about aging in RTT. Continuing longitudinal studies are
      needed to gain more insight into the aging process in RTT.

PMID- 23167725
TI  - Hope for a forgotten people?

PMID- 23167726
TI  - Direct restorative treatment of anterior weared teeth after re-establishment of
      occlusal vertical dimension: a case report.
AB  - OBJECTIVE: The loss of posterior teeth resulting in a lack of stability may lead
      to excessive mandibular load on some points of occlusion of the remaining teeth,
      causing wear. The rehabilitation of these cases must be carefully planned and the
      treatment requires a period of adaptation with a new vertical dimension.
      BACKGROUND: This case report describes the treatment of a patient with a loss of
      almost all posterior inferior teeth and a consequential loss of occlusal vertical
      dimension and accentuated wear of anterior elements. MATERIALS AND METHODS:  
      Provisional removable partial dentures were manufactured and the patient used
      them for a period of adaptation prior to restoration of the anterior teeth. After
      the patient's adaptation with the new occlusal dimension, anterior restorations
      were made using a mycrohibrid resin composite with different color aspects for an
      optimal stratification. RESULTS: The restorations achieved an aesthetic
      configuration with ideal function as the final result and the occlusion showed a
      satisfactory stability for a provisional removable partial dentures. CONCLUSION:
      This article presents an anterior direct rehabilitation approach not only as an
      alternative option, but also as viable and less expensive treatment option with
      an optimally aesthetic and functional result.

PMID- 23167727
TI  - Hyperbaric oxygen therapy treatment for the fixation of implant prosthesis in
      oncology patients irradiated.
AB  - OBJECTIVES: This study aimed to present a clinical report of an irradiated
      oncologic patient who underwent hyperbaric oxygen therapy to be rehabilitated
      with implant-supported prosthesis. MATERIALS AND METHODS: A 67-year-old man was
      admitted at Oral Oncology Center (FOA-UNESP) presenting a lesion on the mouth
      floor. After clinical evaluation, incisional biopsy and histopathological exam, a
      grade II squamous cell carcinoma was diagnosed. The patient was subjected to
      surgery to remove the lesion and partial glossectomy. Afterwards, the
      radiotherapy, in the left/right cervicofacial area of the supraclavicular fossa,
      was conducted. After 3 years of the surgery, the patient was submitted to
      hyperbaric oxygen therapy. Then, four implants were installed in patient's
      mandible. Five months later, an upper conventional complete denture and lower
      full-arch implant-supported prosthesis were fabricated. CONCLUSION: The treatment
      resulted in several benefits such as improving his chewing efficiency, swallowing
      and speech, less denture trauma on the mucosa and improving his self-esteem.

PMID- 23167728
TI  - Nutrition, oral status and dementia.

PMID- 23167730
TI  - Breastfeeding and early brain development: the Generation R study.
AB  - Breastfeeding during infancy is associated with a range of short- and long-term
      health benefits. We examine whether breastfeeding in the first 2 months of life
      is associated with structural markers of brain development in infants from the
      general population. This study was embedded within the Generation R study.
      Cranial ultrasounds were obtained at approximately 7 weeks post-natal age. The
      diameter of the gangliothalamic ovoid, corpus callosum length, ventricular volume
      and head circumference were measured. Maternal reports of breastfeeding were
      obtained at 2 months of age. We examined associations in relation to current
      breastfeeding practices (exclusively breastfed, n = 318, breast- and bottle-fed,
      n = 119, and bottle-fed, n = 243). Analyses were adjusted for head size and
      relevant covariates. Secondary analyses were conducted for breastfeeding history
      (exclusively breastfed, n = 318, breast- and bottle-fed, n = 281, and never
      breastfed, n = 81). Exclusive breastfeeding was associated with more optimal
      brain development compared with babies who were bottle-fed or never breastfed.
      Results were most consistent for gangliothalamic ovoid diameter. Larger
      gangliothalamic ovoid diameters were evident in babies who were exclusively
      breastfed compared with bottle-fed babies [difference between means (95%
      confidence interval) = 0.21(0.02, 0.39), P = 0.02]. Smaller ventricular volume
      and larger head circumference were also found for exclusively breastfed babies.
      Breastfeeding was not significantly associated with corpus callosum length.
      Maternal reports of breastfeeding are associated with more mature brain
      development within the first 2 months of life. Results are most consistent for
      gangliothalamic ovoid diameter, a subcortical structure rich in docosahexaenoic
      acid. Findings also pointed to non-specific neural developmental advantage for
      exclusively breastfed babies.

PMID- 23167731
TI  - The effect of plant identity and the level of plant decay on molecular gut
      content analysis in a herbivorous soil insect.
AB  - Plant roots represent an important food source for soil-dwelling animals, but
      tracking herbivore food choices below-ground is difficult. Here, we present an
      optimized PCR assay for the detection of plant DNA in the guts of invertebrates,
      using general plant primers targeting the trnT-F chloroplast DNA region. Based on
      this assay, we assessed the influence of plant identity on the detectability of
      ingested plant DNA in Agriotes click beetle larvae. Six different plant species
      were fed to the insects, comprising a grass, a legume and four nonlegume forbs.
      Moreover, we examined whether it is possible to amplify DNA of decaying plants
      and if DNA of decayed plant food is detectable in the guts of the larvae. DNA of
      the ingested roots could be detected in the guts of the larvae for up to 72-h
      post-feeding, the maximum digestion time tested. When fed with living plants, DNA
      detection rates differed significantly between the plant species. This may be
      ascribed to differences in the amount of plant tissue consumed, root
      palatability, root morphology and/or secondary plant components. These findings
      indicate that plant identity can affect post-feeding DNA detection success, which
      needs to be considered for the interpretation of molecularly derived feeding
      rates on plants. Amplification of plant DNA from decaying plants was possible as
      long as any tissue could be retrieved from the soil. The consumption of decaying
      plant tissue could also be verified by our assay, but the insects seemed to
      prefer fresh roots over decaying plant material.

PMID- 23167732
TI  - Nurses' perceptions of working according to standardized care plans: a
      questionnaire study.
AB  - AIMS: The aim of this study was to investigate nurses' perceptions of working
      according to standardized care plans (SCPs), regarding usability, documentation,
      quality of care and the implementation process. BACKGROUND: Administrative work
      is an extensive part of nursing practice which leads to decreased time for the
      near patient-related care. In addition, the number of very sick patients with
      short hospital stays has increased. This places new demands on healthcare teams
      to guarantee a high quality of care. For this reason development and use of
      standardized care plans has increased in Sweden during recent years. METHOD: This
      was a cross-sectional survey and 116 registered nurses who had experience of
      working according SCPs answered a questionnaire with the option of providing
      written comments. RESULT: The nurses reported that the use of SCPs facilitated
      their daily work, especially for new employees and worked well as a checklist
      ensuring the quality of care. The documentation was experienced as easy, less
      time consuming with less redundant information. The implementation process of
      SCPs was reported as satisfactory but a majority reported that they were not
      involved in the development of the SCP. However, even though 85.5% reported a
      positive attitude towards working according to an SCP, it was also sometimes
      experienced as inflexible. CONCLUSION: The nurses had overall positive
      perceptions of working according to an SCP mainly in terms of usability,
      documentation and quality of care. The implementation process was not optimal and
      it was doubtful whether the SCP rendered any positive side effects.

PMID- 23167733
TI  - Research that matters - root canal filling and leakage studies.

PMID- 23167735
TI  - Synthesis of enantioenriched aza-proline derivatives through gold(I)-catalyzed
      cyclization of chiral alpha-hydrazino esters.
AB  - A selective gold(I)-catalyzed synthesis of chiral aza-proline derivatives has
      been developed by ring closure of enantioenriched alpha-hydrazino esters bearing
      an alkyne group. These are easily prepared through a synthetic strategy involving
      two key steps: organocatalyzed electrophilic amination of pent-4-ynal with
      dialkyl azodicarboxylate promoted by l-proline and functionalization of the
      triple bond by Sonogashira cross-coupling. This strategy allowed the preparation
      of a range of enantioenriched alpha-hydrazino esters that underwent ring closure
      by using Ph(3)PAuCl/AgBF(4) as a catalytic system. Under these conditions, 5-exo
      dig cyclization was favored over 6-endo-dig and aza-proline derivatives were
      obtained in good yields without epimerization at the stereogenic center.
      Influence of the catalytic system, hydrazine protecting group and alkyne
      substitution on the cyclization step has also been investigated.

PMID- 23167734
TI  - Cord-blood-derived mesenchymal stromal cells downmodulate CD4+ T-cell activation
      by inducing IL-10-producing Th1 cells.
AB  - The mechanisms by which mesenchymal stromal cells (MSCs) induce immunomodulation
      are still poorly understood. In the current work, we show by a combination of
      polymerase chain reaction (PCR) array, flow cytometry, and multiplex cytokine
      data analysis that during the inhibition of an alloantigen-driven CD4+ T-cell
      response, MSCs induce a fraction of CD4+ T-cells to coexpress interferon-gamma
      (IFNgamma) and interleukin-10 (IL-10). This CD4+ IFNgamma+ IL-10+ cell population
      shares properties with recently described T-cells originating from switched Th1
      cells that start producing IL-10 and acquire a regulatory function. Here we
      report that IL-10-producing Th1 cells accumulated with time during T-cell
      stimulation in the presence of MSCs. Moreover, MSCs caused stimulated T-cells to
      downregulate the IFNgamma receptor (IFNgammaR) without affecting IL-10 receptor
      expression. Further, the inhibitory effect of MSCs could be reversed by an anti
      IFNgammaR-blocking antibody, indicating that IFNgamma is one of the major players
      in MSC-induced T-cell suppression. Stimulated (and, to a lesser extent, resting)
      CD4+ T-cells treated with MSCs were able to inhibit the proliferation of
      autologous CD4+ T-cells, demonstrating their acquired regulatory properties.
      Altogether, our results suggest that the generation of IL-10-producing Th1 cells
      is one of the mechanisms by which MSCs can downmodulate an immune response.

PMID- 23167736
TI  - Interaction with culture medium components, cellular uptake and intracellular
      distribution of cobalt nanoparticles, microparticles and ions in Balb/3T3 mouse
      fibroblasts.
AB  - The mechanistic understanding of nanotoxicity requires the physico-chemical
      characterisation of nanoparticles (NP), and their comparative investigation
      relative to the corresponding ions and microparticles (MP). Following this
      approach, the authors studied the dissolution, interaction with medium
      components, bioavailability in culture medium, uptake and intracellular
      distribution of radiolabelled Co forms (CoNP, CoMP and Co(2+)) in Balb/3T3 mouse
      fibroblasts. Co(2+) first saturates the binding sites of molecules in the
      extracellular milieu (e.g., albumin and histidine) and on the cell surface. Only
      after saturation, Co(2+) is actively uptaken. CoNP, instead, are predicted to be
      internalised by endocytosis. Dissolution of Co particles allows the formation of
      Co compounds (CoNP-rel), whose mechanism of cellular internalisation is unknown.
      Co uptake (ranking CoMP > CoNP > Co(2+)) reached maximum at 4 h. Once inside the
      cell, CoNP spread into the cytosol and organelles. Consequently, massive amounts
      of Co ions and CoNP-rel can reach subcellular compartments normally unexposed to
      Co(2+). This could explain the fact that the nuclear and mitochondrial Co
      concentrations resulted significantly higher than those obtained with Co(2+).

PMID- 23167738
TI  - Sealed-capsule irrigation with distilled deionized water to prevent posterior
      capsule opacification--prospective, randomized clinical trial.
AB  - PURPOSE: To evaluate the efficacy and safety of sealed-capsule irrigation (SCI)
      using distilled water (DW) to prevent posterior capsule opacification (PCO).
      MATERIALS AND METHODS: Phacoemulsification was performed in 60 patients. Patients
      were randomly selected into groups. In the control the capsular bag was
      mechanically cleaned (MC), in the DW group DW for 3' in SCI was additionally
      applied. SN60WF IOL was implanted in all eyes. Examinations were performed before
      and 1, 30, 180 days, one and two years after surgery. Uncorrected and corrected
      distance visual acuity (UDVA, CDVA), intraocular pressure (IOP), surgically
      induced astigmatism (K2-SIA), spherical equivalent (SEQ), endothelial cell and
      the complications were examined. Total PCO score in the area of 1 and 3 mm zone
      and capsulorhexis (CAPS) were determined using EPCO 2000. One patient was
      withdrawn from the DW group as he did not report for the examinations. RESULTS:
      As far as safety parameters are concerned, no differences were observed between
      groups in two-year follow-up (p > 0.05). However, in the DW group the endothelial
      cell loss was higher (p < 0.05). Total PCO score differences were observed in
      both groups between the areas (p < 0.05). In the CAPS area, both Total PCO score
      and PCO area were decreased in the DW group (p < 0.05). PCO was also lower within
      3 mm zone in the DW group (p < 0.05). CONCLUSIONS: SCI is a safe procedure and
      the endothelial cells loss can be associated with the Perfect CapsuleTM device
      (Milvella) in the anterior chamber insertion. DW irrigated for 3' reduces PCO in
      long-term follow-up.

PMID- 23167740
TI  - Shrinking and growing: grain boundary density reduction for efficient polysilicon
      thin-film solar cells.
AB  - Polycrystalline Si (poly-Si) thin-film, due to its low Si consumption, low
      substrate cost, and good stability, is an attractive candidate for cost-effective
      solar cells, but the as-deposited poly-Si typically has a columnar structure with
      grain boundaries in between, severely limiting the efficiency of the poly-Si.
      Here, we report a micropillar poly-Si solar cell that utilizes the columnar
      structure of the as-deposited poly-Si grains. We first formed submicrometer
      diameter poly-Si pillars, smaller than the initial grain sizes, and used these
      pillars as the seeds for the subsequent epitaxial growth of Si, which effectively
      reduces grain boundary density in the final poly-Si crystal. In addition, the
      vertically aligned micropillar arrays form radial p-n junctions that further
      mitigate the grain boundary recombination losses by improving the light
      absorption and charge-carrier collection efficiencies. Consequently, the maximum
      efficiency of micropillar poly-Si thin-film solar cells is 6.4%, that is, ~1.5
      times higher than that of the planar cells.

PMID- 23167739
TI  - Combined targeting of AKT and mTOR synergistically inhibits proliferation of
      hepatocellular carcinoma cells.
AB  - BACKGROUND: Due to the frequent dysregulation of the PI3K/AKT/mTOR signaling
      pathway, mTOR represents a suitable therapeutic target in hepatocellular
      carcinoma (HCC). However, emerging data from clinical trials of HCC patients
      indicate that mTOR inhibition by RAD001 (Everolimus) alone has only moderate
      antitumor efficacy which may be due to the feedback activation of AKT after mTOR
      inhibition. In this study, we analyzed the effects of dual inhibition of mTOR and
      AKT on the proliferation of HCC cell lines. In addition, we measured the feedback
      activation of each of the AKT isoforms after mTOR inhibition in HCC cell lines
      and their enzymatic activity in primary samples from HCC patients. METHODS: The
      activation status of specific AKT isoforms in human HCC samples and corresponding
      healthy liver tissue was analyzed using an AKT isoform specific in vitro kinase
      assay. AKT isoform activation after mTOR inhibition was analyzed in three HCC
      cell lines (Hep3B, HepG2 and Huh7), and the impact of AKT signaling on
      proliferation after mTOR inhibition was investigated using the novel AKT
      inhibitor MK-2206 and AKT isoform specific knockdown cells. RESULTS: AKT isoforms
      become differentially activated during feedback activation following RAD001
      treatment. The combination of mTOR inhibition and AKT isoform knockdown showed
      only a weak synergistic effect on proliferation of HCC cell lines. However, the
      combinatorial treatment with RAD001 and the pan AKT inhibitor MK-2206 resulted in
      a strong synergism, both in vitro and in vivo. Moreover, by analyzing primary HCC
      tissue samples we were able to demonstrate that a hotspot mutation (H1047R) of
      PI3KCA, the gene encoding the catalytic subunit of PI3K, was associated with
      increased in vitro kinase activity of all AKT isoforms in comparison to healthy
      liver tissue of the patient. CONCLUSION: Our results demonstrate that dual
      targeting of mTOR and AKT by use of RAD001 and the pan AKT inhibitor MK-2206 does
      effectively inhibit proliferation of HCC cell lines. These data suggest that
      combined treatment with RAD001 and MK-2206 may be a promising therapy approach in
      the treatment of hepatocellular carcinoma.

PMID- 23167741
TI  - Modified agar diffusion bioassay for better quantification of Nisaplin((r)).
AB  - AIMS: To investigate the effect of different well sizes and pre-diffusion times
      at 4  degrees C, on the sensitivity, accuracy and precision of nisin
      quantification by agar diffusion bioassay. METHODS AND RESULTS: Nisin solution
      (0.625-125 MUg ml(-1) ) was filled in wells (3.5 mm or 7 mm diameter) made on
      agar plates inoculated with Micrococcus luteus, followed by pre-diffusion (0, 24,
      48 or 72 h), incubation and measurement of inhibition zone. Regression analysis
      indicated that wells with 3.5 mm diameter had smaller standard deviation and
      higher predictive accuracy, compared to wells with 7 mm diameter. Based on
      Tukey's test, pre-diffusion resulted in significantly different inhibition zones
      at different nisin concentrations. Pre-diffusion also improved sensitivity of the
      assay. Different regression models were considered to explore the relationship
      between inhibition zone and nisin concentration for different pre-diffusion
      times. A spline model was determined to be the best-fit model, and 48 h was the
      best pre-diffusion time. CONCLUSIONS: Wells with 3.5 mm diameter demonstrated
      higher accuracy for nisin quantification compared to wells with 7 mm diameter. 48
      h was the best pre-diffusion time for nisin concentration in the range 0.625-125
      MUg ml(-1) . SIGNIFICANCE AND IMPACT OF THE STUDY: The findings from this study
      will be helpful in quantifying nisin and compounds with antimicrobial properties
      accurately over a wide range of concentrations using agar diffusion bioassay.

PMID- 23167742
TI  - Reversible double oxidation and protonation of the non-innocent bridge in a
      nickel(II) salophen complex.
AB  - Substitution on the aromatic bridge of a nickel(II) salophen complex with
      electron-donating dimethylamino substituents creates a ligand with three stable,
      easily and reversibly accessible oxidation states. The one-electron-oxidized
      product is characterized as a nickel(II) radical complex with the radical bore by
      the central substituted aromatic ring, in contrast to other nickel(II) salen or
      salophen complexes that oxidize on the phenolate moieties. The doubly oxidized
      product, a singlet species, is best described as having an iminobenzoquinone
      bridge with a vinylogous distribution of bond lengths between the dimethylamino
      substituents. Protonation of the dimethylamino substituents inhibits these redox
      processes on the time scale of cyclovoltammetry, but electrolysis and chemical
      oxidation are consistent with deprotonation occurring concomitantly with electron
      transfer to yield the mono- and dioxidized species described above.

PMID- 23167743
TI  - New in silico and conventional in vitro approaches to advance HIV drug discovery
      and design.
AB  - INTRODUCTION: Recently, the new concept of the long-range intermolecular
      interactions in biological systems has been proposed. Combined use of molecular
      modeling techniques and the screening techniques based on the long-range
      interaction concept could significantly improve and accelerate discovery of new
      HIV drugs. However, any hit identified in silico needs to be characterized with
      respect to its biological target by enzymatic studies. Combined use of the in
      silico screening and the enzymatic studies allows an efficient selection of new
      anti-HIV drugs. AREAS COVERED: The focus of this article is on the in silico
      screening of molecular libraries for candidate new HIV drugs, which is based on
      the molecular descriptors determining the long-range interaction between the
      drugs and their therapeutic target. This article also reviews the techniques for
      enzyme kinetic studies which are required for optimization of in silico selected
      candidate anti-HIV drugs. EXPERT OPINION: The novel approach of combining in
      silico screening techniques with enzymatic studies enables the accurate
      measurement of the quantitative descriptors of ligand-enzyme interactions. This
      novel method is a powerful tool for new anti-HIV drug discovery which can also
      reduce the drug development costs.

PMID- 23167745
TI  - Pulmonary hemorrhage in horses seroreactive to leptospirosis in Rio de Janeiro,
      Brazil.

PMID- 23167744
TI  - Downregulation of cannabinoid receptor 1 from neuropeptide Y interneurons in the
      basal ganglia of patients with Huntington's disease and mouse models.
AB  - Cannabinoid receptor 1 (CB(1)  receptor) controls several neuronal functions,
      including neurotransmitter release, synaptic plasticity, gene expression and
      neuronal viability. Downregulation of CB(1)  expression in the basal ganglia of
      patients with Huntington's disease (HD) and animal models represents one of the
      earliest molecular events induced by mutant huntingtin (mHtt). This early
      disruption of neuronal CB(1)  signaling is thought to contribute to HD symptoms
      and neurodegeneration. Here we determined whether CB(1)  downregulation measured
      in patients with HD and mouse models was ubiquitous or restricted to specific
      striatal neuronal subpopulations. Using unbiased semi-quantitative
      immunohistochemistry, we confirmed previous studies showing that CB(1) 
      expression is downregulated in medium spiny neurons of the indirect pathway, and
      found that CB(1)  is also downregulated in neuropeptide Y (NPY)/neuronal nitric
      oxide synthase (nNOS)-expressing interneurons while remaining unchanged in
      parvalbumin- and calretinin-expressing interneurons. CB(1)  downregulation in
      striatal NPY/nNOS-expressing interneurons occurs in R6/2 mice, Hdh(Q150/Q150) 
      mice and the caudate nucleus of patients with HD. In R6/2 mice, CB(1) 
      downregulation in NPY/nNOS-expressing interneurons correlates with diffuse
      expression of mHtt in the soma. This downregulation also occludes the ability of
      cannabinoid agonists to activate the pro-survival signaling molecule cAMP
      response element-binding protein in NPY/nNOS-expressing interneurons. Loss of
      CB(1)  signaling in NPY/nNOS-expressing interneurons could contribute to the
      impairment of basal ganglia functions linked to HD.

PMID- 23167747
TI  - Antimicrobial use in horses undergoing colic surgery.
AB  - BACKGROUND: Recommendations for antimicrobial prophylaxis for surgery are well
      described in human medicine, but information is limited for veterinary practice.
      OBJECTIVE: To characterize antimicrobial use in horses undergoing emergency colic
      surgery. ANIMALS: A total of 761 horses undergoing emergency colic surgery (2001
      2007). METHODS: Retrospective case review. Antimicrobial dose and timing,
      surgical description, and duration of treatment were collected from medical
      records. Associations between antimicrobial use and the occurrence of fever,
      incisional inflammation or infection, catheter-associated complications, or
      Salmonella shedding during hospitalization were analyzed using rank-sum methods
      and logistic regression. RESULTS: A total of 511 (67.2%) horses received an
      inappropriate amount of drug preoperatively. Median time from preoperative dose
      to incision was 70 (IQR 55-90) minutes; median total surgery time was 110 (IQR 80
      160) minutes. Seventy-three horses were euthanized under anesthesia because of
      poor prognosis. Of 688 horses, 438 should have been redosed intraoperatively
      based on the duration of surgery. Only 8 (1.8%) horses were redosed correctly.
      Horses remained on perioperative antimicrobials a median of 3 (IQR 2-4.5) days.
      Antimicrobial therapy was reinstituted in 193 (28.9%) horses, and median days of
      total treatment were 3.8 (IQR 2-6). Signs that led to reinstituting therapy were
      fever (OR 3.13, P = .001) and incisional inflammation/infection (OR 2.95, P =
      .001). Horses in which treatment was reinstituted had 2.3 greater odds of
      shedding Salmonella (P = .003). Increased surgical time was associated with
      longer duration of antimicrobial therapy (OR 1.02, P = .001). CONCLUSIONS AND
      CLINICAL RELEVANCE: Despite published recommendations regarding antimicrobial
      prophylaxis, compliance is poor; improvement might reduce postoperative
      complications.

PMID- 23167750
TI  - Whole exome sequencing in a patient with uniparental disomy of chromosome 2 and a
      complex phenotype.
AB  - Whole exome sequencing and chromosomal microarrays are two powerful technologies
      that have transformed the ability of researchers to search for potentially causal
      variants in human disease. This study combines these tools to search for causal
      variants in a patient found to have maternal uniparental isodisomy of chromosome
      2. This subject has a complex phenotype including skeletal and renal dysplasia,
      immune deficiencies, growth failure, retinal degeneration and ovarian
      insufficiency. Eighteen non-synonymous, rare homozygous variants were identified
      on chromosome 2. Additionally, five genes with compound heterozygous mutations
      were detected on other chromosomes that could lead to a disease phenotype
      independent of the uniparental disomy found in this case. Several candidate genes
      with potential connection to the phenotype are described but none are
      definitively proven to be causal. This study highlights the potential for
      detection of a large number of candidate genes using whole exome sequencing
      complicating interpretation in both the research and clinical settings. Forums
      must be created for publication and sharing of detailed phenotypic and genotypic
      reports to facilitate further biological discoveries and clinical counseling. 

PMID- 23167752
TI  - No effect of host-parasite co-evolution on host range expansion.
AB  - Antagonistic co-evolution between hosts and parasites (reciprocal selection for
      resistance and infectivity) is hypothesized to play an important role in host
      range expansion by selecting for novel infectivity alleles, but tests are
      lacking. Here, we determine whether experimental co-evolution between a bacterium
      (Pseudomonas fluorescens SBW25) and a phage (SBW25Phi2) affects interstrain host
      range: the ability to infect different strains of P. fluorescens other than
      SBW25. We identified and tested a genetically and phenotypically diverse suite of
      co-evolved phage variants of SBW25Phi2 against both sympatric and allopatric co
      evolving hosts (P. fluorescens SBW25) and a large set of other P. fluorescens
      strains. Although all co-evolved phage had a greater host range than the
      ancestral phage and could differentially infect co-evolved variants of P.
      fluorescens SBW25, none could infect any of the alternative P. fluorescens
      strains. Thus, parasite generalism at one genetic scale does not appear to affect
      generalism at other scales, suggesting fundamental genetic constraints on
      parasite adaptation for this virus.

PMID- 23167751
TI  - Leukotriene B4 receptor locus gene characterisation and association studies in
      asthma.
AB  - BACKGROUND: Polymorphisms spanning genes involved in the production of
      leukotriene B4 (LTB4) e.g. ALOX5AP and LTA4H are associated with asthma
      susceptibility, suggesting a role for LTB4 in disease. The contribution of
      LTB4receptor polymorphism is currently unknown. The aim of this study was to
      characterise the genes for the two pivotal LTB4 receptors, LTB4R1 and LTB4R2 in
      lung tissue and determine if polymorphisms spanning these genes are associated
      with asthma and disease severity. METHODS: Rapid amplification of cDNA ends
      (RACE) was used to characterise the LTB4R1 and LTB4R2 gene structure in lung. The
      LTB4R1/2 locus on chromosome 14q11.2 was screened for polymorphic variation. Six
      LTB4R single nucleotide polymorphisms (SNPs) were genotyped in 370 Caucasian
      asthma families and 299 Adult Asthma Individuals (n=1877 total) and were
      evaluated for association with asthma and severity (BTS) outcome measures using
      Family Based Association Test, linear regression and chi square. RESULTS: LTB4R1
      has complex mRNA arrangement including multiple 5'-untranslated exons, suggesting
      additional levels of regulation. Three potential promoter regions across the
      LTB4R1/2 locus were identified with some airway cell specificity. 22 SNPs
      (MAF>0.01) were validated across the LTB4R locus in the Caucasian population.
      LTB4R1 and LTB4R2 SNPs were not associated with asthma susceptibility, FEV1 or
      severity. CONCLUSIONS: LTB4R1 and LTB4R2 shows splice variation in the 5'
      untranslated region and multiple promoter regions. The functional significance of
      this is yet to be determined. Both receptor genes were shown to be polymorphic.
      LTB4R polymorphisms do not appear to be susceptibility markers for the
      development of asthma in Caucasian subjects.

PMID- 23167753
TI  - pH and effects on Streptococcus mutans growth of denture adhesives: an in vitro
      study.
AB  - OBJECTIVES: To evaluate the pH and effects on Streptococcus mutans growth of
      denture adhesives. BACKGROUND: There is little information regarding the pH of
      contemporary adhesives and their influences on S. mutans growth. MATERIALS AND
      METHODS: The adhesives tested were Polident(r) cream, Protefix(r) cream and
      Protefix(r) powder. Samples of each adhesive were added to deionized water to
      produce solutions of 10.0, 5.0, 2.5 and 1.0% w/v (cream formulations) or 5.0,
      2.5,1.0 and 0.5% (powder formulation). The pH values were measured immediately
      after preparation and at 1-, 2-, 3-, 6-, 12-, and 24-h intervals using a digital
      pH meter. Streptococcus mutans UA159 was inoculated in the Brain Heart Infusion
      medium with or without the adhesive extracts (control). Bacterial growth was
      observed by measuring absorption at 600 nm every 1 h for 12 h using a
      spectrophotometer. RESULTS: The tested adhesives generally remained relatively pH
      stable over 24 h, ranging from 5.5 to 7.0. There were no statistically
      significant differences in S. mutans growth rates between the extract-treated and
      control cultures (p>0.5). CONCLUSIONS: Some adhesives produce a pH below the
      critical pH of hydroxyapatite and may not be suitable for patients with natural
      teeth. None of the tested adhesives significantly affect S. mutans growth.

PMID- 23167754
TI  - The World Health Organization-United Nations Population Fund Strategic
      Partnership Programme's implementation of family planning guidelines and tools in
      Asia-Pacific countries.
AB  - AIM: The aim of this study was to assess the impact of the Strategic Partnership
      Programme, a collaboration between the World Health Organization and the United
      Nations Population Fund to improve evidence-based guidance for country programs
      through the introduction of selected practice guidelines to improve sexual and
      reproductive health. METHODS: Information for this report is from questionnaires
      sent to Ministries of Health in 2004 (baseline assessment) and in 2007
      (assessment of outcome), annual country reports and personal communication with
      focal points from Ministries of Health and World Health Organization regional and
      country offices. RESULTS: Following the Strategic Partnership Programme, family
      planning guidance was used extensively to: formulate and update reproductive
      health policy; update standards and guidelines; improve training curricula;
      conduct training activities; develop advocacy and communication materials; and
      promote change in service. CONCLUSION: The Strategic Partnership Programme was
      successful in promoting the introduction of evidence-based guidelines for
      reproductive health in several Asian countries. The countries that adapted the
      family planning guidance observed an increase in demand for contraceptives
      commodities.

PMID- 23167755
TI  - Clinical investigation on axial versus tilted implants for immediate fixed
      rehabilitation of edentulous arches: preliminary results of a single cohort
      study.
AB  - PURPOSE: The purpose of this clinical investigation was to evaluate full-arch
      fixed-dental restorations supported by immediate loaded axial and tilted implants
      in a single-cohort study. Survival rate of axial and tilted implants was
      compared. MATERIALS AND METHODS: From 2006 to 2010, 30 patients were recruited
      and treated with dental implants. Provisional fixed-dental prostheses were screw
      retained over axial or axial and tilted implants within 24 hours after surgery.
      Follow-ups at 6, 12, and 24 months and annually up to 5 years were scheduled, and
      radiographic evaluation of peri-implant bone level changes was conducted.
      RESULTS: Thirty patients (20 females and 10 males) were followed up for an
      average of 44 months (range 18-67 months). Six patients received both upper and
      lower implant rehabilitations, resulting in 36 restorations. A total of two
      hundred two implants were placed (maxilla = 118; mandible = 84) and 46% of the
      fixtures were evaluated at the 4-year recall. Four axial implants were lost in
      three patients, leading to 98.02% implant (97.56% axial implants and 100% tilted
      implants) and 100% prosthetic cumulative survival rate, respectively. No
      significant difference in marginal bone loss was found between tilted and axial
      implants in both jaws at 1-year evaluation. CONCLUSIONS: Midterm results
      confirmed that immediate loading of axial and tilted implants provides a viable
      treatment modality for the rehabilitation of edentulous arches.

PMID- 23167757
TI  - N-linked glycosylation modulates dimerization of protein disulfide isomerase
      family A member 2 (PDIA2).
AB  - Protein disulfide isomerase (PDI) family members are important enzymes for the
      correct folding and maturation of proteins that transit or reside in the
      endoplasmic reticulum (ER). The human PDI family comprises at least 19 members
      that differ in cell type expression, substrate specificity and post-translational
      modifications. PDI family A member 2 (PDIA2, previously known as PDIp) has a
      similar domain structure to prototypical PDI (also known as PDIA1), but the
      function and post-translational modifications of PDIA2 remain poorly understood.
      Unlike most PDI family members, PDIA2 contains three predicted N-linked
      glycosylation sites. By site-directed mutagenesis and enzymatic deglycosylation,
      we show here that all three Asn residues within the potential N-linked
      glycosylation sites of human PDIA2 (N127, N284 and N516) are glycosylated in
      human cells. Furthermore, mutation of N284 to glycosylation-null Gln increases
      formation of a highly stable disulfide-bonded PDIA2 dimer. Nevertheless, in HeLa
      cells, both wild-type and N127/284/516Q mutant PDIA2 proteins localize to the ER,
      but not the ER-Golgi intermediate compartment, suggesting that glycosylation is
      important for PDIA2 protein-protein interactions but not subcellular
      localization. Finally, we identified human major histocompatibility complex class
      1 antigens (HLA-A,B,C) as potential binding partners of PDIA2, suggesting an
      involvement for PDIA2 in antigen presentation in addition to its previously
      described roles in autoimmunity and Parkinson's disease. These results further
      characterize this poorly defined member of the PDI family.

PMID- 23167758
TI  - Essential oils composition of two Sicilian cultivars of Opuntia ficus-indica (L.)
      Mill. (Cactaceae) fruits (prickly pear).
AB  - The essential oils composition of the skin, pulp and seeds from fruits of two
      Sicilian cultivars of Opuntia ficus-indica (cv. Sanguigna and cv. Surfarina) has
      been obtained by hydrodistillation and the possible antioxidant, antimicrobial
      and semiochemical roles have been investigated comparing the data with those
      reported in the literature. The presence of antioxidants and antimicrobials found
      in this study increases the spectrum of compounds that have beneficial properties
      in O. ficus-indica. In addition, several compounds identified in this study have
      been reported to influence the behaviour of Ceratitis capitata, a phytophagous
      pest which causes severe damages to several crops including O. ficus-indica and
      the kairomonal activity of the odour of the fruits seems provided by a blend of
      compounds found in the various matrices analysed. 

PMID- 23167759
TI  - Internationally educated nurses' experiences in a hospital in England: an
      exploratory study.
AB  - BACKGROUND: The recruiting of internationally educated nurses (IENs) to work in
      the National Health Service (NHS) in the United Kingdom (UK) is not a new
      phenomenon. Such practices have its roots in the 1940s when the NHS was first
      incepted. OBJECTIVE: The aim of this study was to gain an understanding of IENs'
      experiences of working in the NHS in England. METHODS: Phenomenology in
      particular, Heidegger, was the approach adopted, and the study consisted of two
      phases in which twelve individuals' interviews were conducted in phase one. The
      findings from this phase informed the second phase where four focus group
      interviews were used. The data for both phases were thematically analysed.
      RESULTS: Six themes emerged following data analysis, namely Leaving a familiar
      world, Being thrown into an unfamiliar world, Encountering marginalisation and
      experiencing inequalities in the world, Surviving in an everyday world, Living in
      an everyday world and Making a new world. CONCLUSION: Internationally educated
      nurses encountered a number of challenges to their working practices in an
      English hospital, and there is a need for both IENs and home-grown nurses to
      adapt to each other cultural differences.

PMID- 23167760
TI  - Characterization of protein higher order structure using vibrational circular
      dichroism spectroscopy.
AB  - Better understanding of protein higher order structures (HOS) is of major
      interest to researchers in the field of biotechnology and biopharmaceutics.
      Monitoring a protein's HOS is crucial towards understanding the impact of
      molecular conformation on the biotechnological application. In addition,
      maintaining the HOS is critical for achieving robust processes and developing
      stable formulations of therapeutic proteins. Loss of HOS contributes to increased
      aggregation, enhanced immunogenicity and loss of function. Selecting the proper
      biophysical methods to monitor the secondary and tertiary structures of
      therapeutic proteins remains the central question in this field. In this study,
      both Fourier Transform Infrared (FTIR) and vibrational circular dichroism (VCD)
      spectroscopy are employed to characterize the secondary structures of various
      proteins as a function of temperature and pH. Three proteins with different
      secondary structures were examined, human serum albumin (HSA), myoglobin, and the
      monoclonal antibody, ofatumumab. This work demonstrates that VCD is useful
      technique for monitoring subtle secondary structure changes of protein
      therapeutics that may occur during processing or handling.

PMID- 23167761
TI  - Chloramphenicol enhances IDUA activity on fibroblasts from mucopolysaccharidosis
      I patients.
AB  - Mucopolysaccharidosis I (MPS I) is a genetic disorder caused by mutations on
      alpha-L-iduronidase (IDUA) gene, leading to low or null enzyme activity. As
      nonsense mutations are present in about two thirds of the patients, stop codon
      read through (SCRT) is a potential alternative to achieve enhanced enzyme
      activity. This mechanism suppresses premature stop codon mutations allowing the
      protein to be fully translated. Chloramphenicol is a peptidyl transferase
      inhibitor able to induce readthrough and is efficient in cross the blood brain
      barrier. In this work, fibroblasts from MPS I patients (p.W402X/p.W402X;
      p.R89W/p.W402X and p.Q70X/c.1739-1g > t) were treated with chloramphenicol, which
      resulted in 100-fold increase on IDUA activity on compound heterozygous
      fibroblasts. cDNA sequencing showed that only the alleles without the nonsense
      mutation were being amplified, even after treatment, leading us to suggest that
      the nonsense alleles were targeted to nonsense-mediated mRNA decay and that
      chloramphenicol acts through a mechanism other than SCRT.

PMID- 23167762
TI  - Association of CYP46 gene polymorphism with sporadic Alzheimer's disease in
      Chinese Han populations: a meta-analysis.
AB  - It is well known that genetic variants play an important role in the pathogenesis
      of Alzheimer's disease (AD). Recently, several studies have found that an
      intronic single-nucleotide polymorphism (SNP) in cholesterol 24S-hydroxylase
      (CYP46) gene was associated with sporadic AD (SAD). Within the CYP46 gene, the
      most well-studied SNP that has been found to be associated with an increased risk
      for SAD in Caucasians is the intronic SNP rs754203. Subsequently, other
      researchers have attempted to validate this finding in Chinese Han populations.
      However, these studies have produced both negative and positive results. To
      derive a more precise estimation for whether an association exists between
      rs754203 and SAD in the Chinese Han population, we performed the present meta
      analysis of six case-control studies published up to July 2012 by searching the
      Medline, AlzGene, CNKI, and Wan Fang databases. Pooled odds ratios (ORs) and 95%
      confidence intervals (95% CIs) were calculated for four genetic models (allelic
      model: T vs. C; additive model: TT vs. CC; recessive model: TT + TC vs. CC;
      dominant model: TC + CC vs. TT) in the six studies, which included a total of
      1187 cases and 1283 controls. The statistical analysis showed no significant
      differences in rs754203 between patients and controls for any of the four genetic
      models (p > 0.05 for each model). In conclusion, despite several limitations,
      this meta-analysis indicates that the CYP46 gene SNP rs754203 is not
      significantly associated with SAD susceptibility in Chinese Han populations.

PMID- 23167763
TI  - Diminished vagal activity and blunted diurnal variation of heart rate dynamics in
      posttraumatic stress disorder.
AB  - Affected autonomic heart regulation is implicated in the pathophysiology of
      cardiovascular diseases and is associated with posttraumatic stress disorder
      (PTSD). However, although sympathetic hyperactivation has been repeatedly shown
      in PTSD, research has neglected parasympathetic function. The objective of this
      study is the long-term assessment of heart rate (HR) dynamics and its diurnal
      changes as an index of autonomic imbalance in PTSD. Since tonic parasympathetic
      activity underlies long-range correlation of heartbeat interval fluctuations in
      the healthy state, we included nonlinear (unifractal) analysis as an important
      and sensitive readout to assess functional alterations. We conducted
      electrocardiogram recordings over a 24-h period in 15 deployed male subjects with
      moderate to high levels of combat exposure (PTSD: n = 7; combat controls: n = 8)
      in the supine position. HR dynamics were assessed in two 5-h sub-epochs in the
      time and frequency domains, and by nonlinear analysis based on detrended
      fluctuation analysis. Psychiatric symptoms were assessed using structured
      interviews, including the Clinician Administered PTSD Scale. Subjects with PTSD
      showed significantly higher baseline HR, higher LF/HF ratio in the frequency
      domain, blunted differences between day and night-time measures, as well as a
      higher scaling coefficient alphafast during the day, indicating diminished tonic
      parasympathetic activity. Diminished diurnal differences and blunted tonic
      parasympathetic activity altering HR dynamics suggest central neuroautonomic
      dysregulation that could represent a possible link to increased cardiovascular
      disease in PTSD.

PMID- 23167764
TI  - Impaired systemic vascular endothelial function in patients with branch retinal
      vein occlusion.
AB  - PURPOSE: To evaluate systemic endothelial function in patients with branch
      retinal vein occlusion (BRVO). METHODS: Twenty-seven patients with BRVO (BRVO
      group, 8 men, 19 women; mean age, 65.4 +/- 1.3), 10 patients with systemic
      hypertension and no other systemic or ocular disease (hypertension group, 6 men,
      4 women; mean age, 70.4 +/- 2.2), and 10 healthy volunteers (healthy group, 3
      men, 7 women; mean age, 63.8 +/- 2.1) were enrolled. We excluded patients with
      diabetes mellitus and current smokers. Using high-resolution ultrasonographic
      imaging, we evaluated the brachial artery (mm) to evaluate the flow-mediated
      vasodilation (FMD) by measuring the diameter of the brachial artery during
      reperfusion after arterial occlusion. RESULTS: There were no significant
      differences among the three groups in age (p = 0.98), sex (p = 0.21), or the
      baseline diameter of the brachial artery (p = 0.11). The group-averaged FMD value
      decreased significantly in the BRVO group (4.6 +/- 0.4%) compared to the
      hypertension group (8.0 +/- 0.8%, p < 0.01) and the healthy group (6.9 +/- 0.6%,
      p < 0.05). Multiple logistic regression analysis identified lower FMD as an
      independent risk factor for BRVO. CONCLUSIONS: The results suggested that BRVO is
      associated with generalized endothelial dysfunction and that impaired systemic
      endothelial function may be associated with BRVO.

PMID- 23167765
TI  - Nanostructured lipid carriers: a potential drug carrier for cancer chemotherapy.
AB  - Nanotechnology having developed exponentially, the aim has been on therapeutic
      undertaking, particularly for cancerous disease chemotherapy. Nanostructured
      lipid carriers have attracted expanding scientific and commercial vigilance in
      the last couple of years as alternate carriers for the pharmaceutical
      consignment, particularly anticancer pharmaceuticals. Shortcomings often came
      across with anticancer mixtures, such as poor solubility, normal tissue toxicity,
      poor specificity and steadiness, as well as the high incidence rate of
      pharmaceutical resistance and the rapid degradation, need of large-scale output
      procedures, a fast release of the pharmaceutical from its carrier scheme,
      steadiness troubles, the residues of the organic solvents utilized in the output
      method and the toxicity from the polymer with esteem to the carrier scheme are
      anticipated to be overcome through use of the Nanostructured Lipid Carrier. In
      this review the benefits, types, drug release modulations, steadiness and output
      techniques of NLCs are discussed. In supplement, the function of NLC in cancer
      chemotherapy is presented and hotspots in research are emphasized. It is foreseen
      that, in the beside future, nanostructured lipid carriers will be further
      advanced to consign cytotoxic anticancer compounds in a more efficient, exact and
      protected manner.

PMID- 23167766
TI  - Lung cancer chemoprevention: difficulties, promise and potential agents?
AB  - INTRODUCTION: In a variety of cancers there is evidence that specific regimens
      can prevent or significantly delay the development of cancer. Thus, for breast
      cancer (ER+) use of SERMs or aromatase inhibitors can substantially decrease
      tumor incidence. For cervical cancer, HPV vaccination will inhibit long term
      cancer incidence. For colon cancer, the second greatest cancer killer,
      administration of aspirin and other NSAIDs decreases advanced colon adenomas in
      Phase II trials and epidemiologic data support their ability to prevent colon
      cancer. To date prevention trials in the area of lung cancer have shown minimal
      efficacy. AREAS COVERED: The paper examines and discusses in greater detail
      certain promising agents which the authors have tested either preclinically and
      or in early phase clinical trials. These agents include RXR agonists, EGFr
      inhibitors, NSAIDs and Triterpenoids. Other agents including glucocorticoids,
      pioglitazone and iloprost are briefly mentioned. In addition, the paper presents
      various types of potential Phase II lung cancer prevention trials and describes
      their strengths and weaknesses. The potential use of various biomarkers as
      endpoints in trials e.g. histopathology, non-specific biomarkers (e.g., Ki67,
      cyclin D expression, apoptosis) and molecular biomarkers (e.g. specific
      phosphorylated proteins, gene expression etc.) is presented. Finally, we examine
      at least one approach, the use of aerosols, which may diminish the systemic
      toxicity associated with certain of these agents. EXPERT OPINION: The manuscript
      presents: a) a number of promising agents which appear applicable to further
      Phase II prevention trials; b) approaches to defining potential preventive agents
      as well; c) approaches which might mitigate the side effects associated with
      potential agents most specifically the use of aerosols. Finally, we discuss
      biomarker studies both preclinical and clinical which might help support
      potential Phase II trials. The particular appeal to the preclinical studies is
      that they can be followed to a tumor endpoint. We hope that this will give the
      reader further background and allow one to appreciate the potential and some of
      the hurdles associated with lung cancer chemoprevention.

PMID- 23167767
TI  - Fabrication of 3-dimensional cellular constructs via microstereolithography using
      a simple, three-component, poly(ethylene glycol) acrylate-based system.
AB  - A novel method for the production of inhibitor- and solvent-free resins suitable
      for three-dimensional (3D) microstereolithography is reported. Using an exemplar
      poly(ethylene glycol)-based resin, the control of features in the X, Y, and Z
      planes is demonstrated such that complex structures can be manufactured. Human
      mesenchymal stem cells cultured on the manufactured scaffolds remained viable
      during the 7 day assessment period, with proliferation rates comparable to those
      observed on tissue culture polystyrene. These data suggest that this novel, yet
      simple, method is suitable for the production of 3D scaffolds for tissue
      engineering and regenerative medicine applications.

PMID- 23167768
TI  - Salmonella serotype diversity and seasonality in urban and rural streams.
AB  - AIMS: To investigate the prevalence, seasonality and genetic diversity of
      Salmonella enterica serotypes, particularly those of human and veterinary health
      significance, in urban and rural streams. METHODS AND RESULTS: Using a swab
      collection technique and multiple culture media for isolation, Salmonella were
      detected in 78.4% of water samples (November 2003 to July 2005) taken from urban
      and rural/agricultural streams in the Grand River watershed (Ontario, Canada).
      Among 235 isolates, there were 38 serotypes, with the predominant serotypes and
      phagetypes (PT) being Salmonella Typhimurium PT 104 and Salmonella Heidelberg PT
      19. These are also the most common Salmonella serotypes found in humans and farm
      animals locally and across Canada, a trend not commonly reported. The urban
      stream had more frequent Salmonella occurrence, greater serotype diversity and
      greater genetic variability (based on pulsed field gel electrophoresis) of
      specific strains compared with the rural/agricultural streams. Distinct
      seasonality in serotypes of health significance was observed only in the
      rural/agricultural streams, which is likely a reflection of seasonal source
      inputs in these watersheds. Despite the lower occurrence of these strains in
      stream water in the colder months, laboratory studies did not support reduced
      survival of Salm. Typhimurium and Salm. Heidelberg at lower temperatures,
      although survival differences were observed with other serotypes. CONCLUSIONS: A
      diverse range of Salmonella serotypes and PT were obtained from both urban and
      rural/agricultural streams, with the predominant strains being those most
      frequently associated with human and veterinary disease in Canada. SIGNIFICANCE
      AND IMPACT OF THE STUDY: The ubiquitous nature of Salmonella in water and the
      predominance of serotypes/PT of human or veterinary health significance suggest
      that the aquatic environment is a reservoir for this bacterium and could be
      involved in the transport and dissemination of this pathogen between hosts.

PMID- 23167769
TI  - Informal musical activities are linked to auditory discrimination and attention
      in 2-3-year-old children: an event-related potential study.
AB  - The relation between informal musical activities at home and electrophysiological
      indices of neural auditory change detection was investigated in 2-3-year-old
      children. Auditory event-related potentials were recorded in a multi-feature
      paradigm that included frequency, duration, intensity, direction, gap deviants
      and attention-catching novel sounds. Correlations were calculated between these
      responses and the amount of musical activity at home (i.e. musical play by the
      child and parental singing) reported by the parents. A higher overall amount of
      informal musical activity was associated with larger P3as elicited by the gap and
      duration deviants, and smaller late discriminative negativity responses elicited
      by all deviant types. Furthermore, more musical activities were linked to smaller
      P3as elicited by the novel sounds, whereas more paternal singing was associated
      with smaller reorienting negativity responses to these sounds. These results
      imply heightened sensitivity to temporal acoustic changes, more mature auditory
      change detection, and less distractibility in children with more informal musical
      activities in their home environment. Our results highlight the significance of
      informal musical experiences in enhancing the development of highly important
      auditory abilities in early childhood.

PMID- 23167770
TI  - The effects of serum potassium and magnesium levels in a patient with Gitelman's
      syndrome on the timing of ventricular wall motion and the pattern of ventricular
      strain and torsion.
AB  - Gitelman's syndrome is a primary renal tubular hypokalemic metabolic alkalosis.
      Hypokalemia and hypomagnesemia can cause cardiac tissue excitability and
      conduction. Global ventricular mechanical function is directly related to the
      contractile properties of cardiac myocytes, which are largely dependent on the
      flow of ions such as potassium and magnesium. Here, we show that increased levels
      of potassium, in addition to magnesium, in a patient with Gitelman's syndrome
      significantly impacts the timing of ventricular wall motion and the pattern of
      ventricular strain and torsion. Two-dimensional speckle tracking echocardiography
      was used for evaluation of the hypokalemic-hypomagnesemic period (first day) and
      third day after potassium chloride and magnesium replacement therapy. The
      transthoracic echocardiography showed that the percent ejection fraction was
      similar in hypokalemic-hypomagnesemic (63%) and normokalemic-normomagnesemic
      (after potassium and magnesium therapy, 67%) hearts. However, decreased left
      ventricular apical 4-chamber peak systolic longitudinal strain, left ventricle
      global peak systolic strain, and global torsion values increased after potassium
      chloride and magnesium replacement therapy.

PMID- 23167771
TI  - Antiproteinuric effect of add-on paricalcitol in CKD patients under maximal
      tolerated inhibition of renin-angiotensin system: a prospective observational
      study.
AB  - BACKGROUND: Whether paricalcitol (PCT) reduces proteinuria in the presence of
      intensified inhibition of Renin-Angiotensin-System (RAS) is poorly studied. We
      evaluated the antiproteinuric effect of PCT in non-dialysis chronic kidney
      disease (CKD) patients with proteinuria greater than 0.5 g/24 h persisting
      despite anti-RAS therapy titrated to minimize proteinuria in the absence of
      adverse effects. METHODS: Forty-eight CKD patients were studied in the first six
      months of add-on oral PCT (1 mcg/day) and three months after drug withdrawal.
      RESULTS: Males were 87.5%, age 63 +/- 14 yrs, systolic/diastolic blood pressure
      (BP) 143 +/- 22/78 +/- 11 mmHg, eGFR 29.7 +/- 14.5 mL/min/1.73 m(2), diabetes
      40%, and cardiovascular disease 38%. At referral in the center (28 months prior
      to study baseline), proteinuria was 2.44 (95% CI 1.80-3.04) g/24 h with 6
      patients not receiving any anti-RAS and 42 treated with a single agent, at low
      dosage in most cases. At study baseline, twenty patients were under 2-3 anti-RAS
      drugs while twenty-eight received 1 agent at full dose and proteinuria resulted
      to be reduced versus referral to 1.23 g/24 h (95%CI 1.00-1.51). Six months of add
      on PCT significantly decreased proteinuria to 0.61 g/24 h (95%CI 0.40-0.93), with
      levels less than 0.5 g/24 h achieved in 37.5% patients, in the absence of changes
      of BP and GFR. Proteinuria recovered to basal value after drug withdrawal. The
      extent of antiproteinuric response to PCT was positively associated with
      diabetes, eGFR and daily Na excretion (R(2) = 0.459, P < 0.0001). PTH decreased
      from 201 (IQR 92-273) to 83 (IQR 50-189) pg/mL. CONCLUSIONS: In CKD patients, add
      on PCT induces a significant reduction of proteinuria that is evident despite
      intensified anti-RAS therapy and larger in the presence of diabetes, higher GFR
      and unrestricted salt intake.

PMID- 23167772
TI  - Organocatalytic asymmetric Michael addition of oxindoles to nitroolefins for the
      synthesis of 2,2-disubstituted oxindoles bearing adjacent quaternary and tertiary
      stereocenters.
AB  - A bifunctional thiourea-catalyzed Michael addition of activated indolin-3-ones to
      nitroolefins has been developed. The synthetically useful 2,2-disubstituted
      indolin-3-one derivatives with vicinal chiral quaternary-tertiary stereocenters
      were obtained in high yields with excellent stereoselectivities. The adduct can
      be readily transformed into a structurally interesting heterocyclic architecture
      by means of further synthetic elaboration.

PMID- 23167773
TI  - Electrical probing of magnetic phase transition and domain wall motion in single
      crystalline Mn5Ge3 nanowire.
AB  - In this Letter, the magnetic phase transition and domain wall motion in a single
      crystalline Mn(5)Ge(3) nanowire were investigated by temperature-dependent
      magneto-transport measurements. The ferromagnetic Mn(5)Ge(3) nanowire was
      fabricated by fully germaniding a single-crystalline Ge nanowire through the
      solid-state reaction with Mn contacts upon thermal annealing at 450  degrees C.
      Temperature-dependent four-probe resistance measurements on the Mn(5)Ge(3)
      nanowire showed a clear slope change near 300 K accompanied by a magnetic phase
      transition from ferromagnetism to paramagnetism. The transition temperature was
      able to be controlled by both axial and radial magnetic fields as the external
      magnetic field helped maintain the magnetization aligned in the Mn(5)Ge(3)
      nanowire. Near the magnetic phase transition, the critical behavior in the 1D
      system was characterized by a power-law relation with a critical exponent of
      alpha = 0.07 +/- 0.01. Besides, another interesting feature was revealed as a
      cusp at about 67 K in the first-order derivative of the nanowire resistance,
      which was attributed to a possible magnetic transition between two noncollinear
      and collinear ferromagnetic states in the Mn(5)Ge(3) lattice. Furthermore,
      temperature-dependent magneto-transport measurements demonstrated a hysteretic,
      symmetric, and stepwise axial magnetoresistance of the Mn(5)Ge(3) nanowire. The
      interesting features of abrupt jumps indicated the presence of multiple domain
      walls in the Mn(5)Ge(3) nanowire and the annihilation of domain walls driven by
      the magnetic field. The Kurkijarvi model was used to describe the domain wall
      depinning as thermally assisted escape from a single energy barrier, and the
      fitting on the temperature-dependent depinning magnetic fields yielded an energy
      barrier of 0.166 eV.

PMID- 23167774
TI  - Complete remission of recurrent ovarian clear cell carcinoma by chemotherapy with
      bevacizumab, trabectedin and oxaliplatin.
AB  - Clear cell carcinoma of the ovary has shown an exceedingly chemo-resistant
      phenotype, especially in cases that are recurrent or refractory to previous
      therapy. Also, progression-free survival was less than 6 months, even in the
      patients that achieved response when they were treated with conventional anti
      cancer cytotoxic agents. We present a case with recurrent and refractory ovarian
      clear cell carcinoma that achieved complete remission using a combination of
      bevacizumab, trabectedin and oxaliplatin. The progression-free interval of the
      patient is over 30 months, and she is still receiving the combination therapy
      without toxicities of more than grade 2.

PMID- 23167775
TI  - Knowledge of the Genetic Information Nondiscrimination act among individuals
      affected by Huntington disease.
AB  - The Genetic Information Nondiscrimination Act (GINA) of 2008 was the first US
      legislation to address genetic discrimination. We sought to assess understanding
      of GINA among individuals affected by the autosomal dominant condition,
      Huntington disease (HD). We conducted a cross-sectional survey of individuals
      with varying risk of HD to assess their familiarity with GINA. As a control,
      individuals were surveyed about their familiarity with the Health Insurance
      Portability and Accountability Act (HIPAA). Those who reported familiarity with
      GINA were asked about their knowledge of specific provisions of the legislation.
      The survey was offered to 776 participants and completed by 410 (response rate
      53%). Respondents across all groups were less familiar with GINA (41% slightly,
      somewhat, or very familiar) than with HIPAA (65%; p < 0.0001). Of individuals
      with or at risk for HD who reported some familiarity with GINA, less than half
      correctly identified GINA's protections, and less than 15% correctly identified
      its limitations. Thus, among individuals affected by HD, familiarity with and
      knowledge of GINA are low. The effectiveness of the legislation may be limited by
      this lack of knowledge. 

PMID- 23167776
TI  - Prevalence of torus mandibularis among a group of elderly Japanese and its
      relationship with occlusal force.
AB  - OBJECTIVE: To examine the prevalence of torus mandibularis (TM) and identify
      clinical factors associated with its presence. MATERIALS AND METHODS: A total of
      664 Japanese adults over age 60 were studied by means of a questionnaire and
      clinical examination. RESULTS: In all, 197 subjects (29.7%) had TM. We found a
      significant association between the presence of TM and torus palatinus (TP; 45.1%
      vs. 26.5%, p<0.001). Moreover, occlusal force with TM was significantly higher
      than without TM (p<0.05). Logistic regression adjusted for age and occlusal force
      revealed a significant relationship between TM and occlusal force and TP
      [p=0.005, odds ratio (OR)=2.44; p<0.001, OR=2.66, respectively]. CONCLUSION: This
      study suggests that there is a relationship between TM and factors related to
      occlusal factor.

PMID- 23167777
TI  - Hexagonally ordered KLaF4 host: phase-controlled synthesis and luminescence
      studies.
AB  - Experiments resulting in the successful synthesis of hexagonally ordered KLaF(4)
      have been described for the first time. Syntheses from three different lanthanum
      precursors and KF under nonaqueous conditions and at atmospheric pressure are
      presented. The temperature, time of the fluorination reactions, and lanthanum
      precursor influenced the formation of hexagonal KLaF(4). While La(O(i)Pr)(3) and
      La(acac)(3) yielded hexagonal KLaF(4) by their reaction with KF in methanol at 65
      degrees C, LaCl(3) favored only the formation of cubic KLaF(4) at 25  degrees C
      (room temperature). Size-induced phase transformation from cubic KLaF(4) to its
      hexagonal polymorph has been proposed for the reactions involving La(acac)(3) and
      La(O(i)Pr)(3) and KF. Rietveld refinement of the powder X-ray diffraction pattern
      of the hexagonally ordered KLaF(4) was successfully carried out in space group
      P62m (No. 189) with lattice constants a = 6.5842(3) A and c = 3.8165(3) A. A
      relatively lower effective phonon energy of 262 cm(-1) observed for the
      hexagonally ordered KLaF(4) (determined from its Raman spectrum) suggests its
      potential as a host for optically active elements with the possibility of
      minimized nonradiative processes. The hexagonal KLaF(4) sample was doped with
      Er(3+) ion (3 mol %) and systematically investigated by diffuse reflectance,
      normal emission, and upconversion studies. Strong green emission ((4)S(3/2),
      (2)H(11/2) -> (4)I(15/2)) has been observed upon 980 and 460 nm excitation. A
      highly transparent light-emitting polymer [poly(methyl methacrylate)] composite
      containing hexagonal KLaF(4):Er(3+) phosphor has also been effectively
      demonstrated for many potential applications.

PMID- 23167778
TI  - Liver fat content is linked to inflammatory changes in subcutaneous adipose
      tissue in type 2 diabetes patients.
AB  - BACKGROUND: Patients with type 2 diabetes mellitus (T2DM) are typically
      overweight and have an increased liver fat content (LFAT). High LFAT may be
      explained by an increased efflux of free fatty acids from the adipose tissue,
      which is partly instigated by inflammatory changes. This would imply an
      association between inflammatory features of the adipose tissue and liver fat
      content. OBJECTIVE: To analyse associations between inflammatory features of the
      adipose tissue and liver fat content. DESIGN: A cross-sectional study. PATIENTS:
      Twenty-seven obese patients with insulin-treated T2DM were studied. MEASUREMENTS:
      LFAT content was measured by proton magnetic resonance spectroscopy. A
      subcutaneous (sc) fat biopsy was obtained to determine morphology and protein
      levels within adipose tissue. In addition to fat cell size, the percentage of
      macrophages and the presence of crown-like structures (CLSs) within sc fat were
      assessed by CD68-immunohistochemical staining. RESULTS: Mean LFAT percentage was
      11.1 +/- 1.7% (range: 0.75-32.9%); 63% of the patients were diagnosed with an
      elevated LFAT (upper range of normal <=5.5%). Whereas adipocyte size did not
      correlate with LFAT, 3 of 4 subjects with CLSs in sc fat had elevated LFAT and
      the percentage of macrophages present in sc adipose tissue was positively
      associated with LFAT. Protein concentrations of adiponectin within adipose tissue
      negatively correlated with LFAT. Adipose tissue protein levels of the key
      inflammatory adipokine plasminogen activator inhibitor-1 (PAI-1) were positively
      associated with LFAT. CONCLUSIONS: Several pro-inflammatory changes in sc adipose
      tissue associate with increased LFAT content in obese insulin-treated patients
      with T2DM. These findings suggest that inflammatory changes at the level of the
      adipose tissue may drive liver fat accumulation.

PMID- 23167779
TI  - Xylanase XYN IV from Trichoderma reesei showing exo- and endo-xylanase activity.
AB  - A minor xylanase, named XYN IV, was purified from the cellulolytic system of the
      fungus Trichoderma reesei Rut C30. The enzyme was discovered on the basis of its
      ability to attack aldotetraohexenuronic acid (HexA-2Xyl-4Xyl-4Xyl,
      HexA(3)Xyl(3)), releasing the reducing-end xylose residue. XYN IV exhibited
      catalytic properties incompatible with previously described endo-beta-1,4
      xylanases of this fungus, XYN I, XYN II and XYN III, and the xylan-hydrolyzing
      endo-beta-1,4-glucanase EG I. XYN IV was able to degrade several different beta
      1,4-xylans, but was inactive on beta-1,4-mannans and beta-1,4-glucans. It showed
      both exo-and endo-xylanase activity. Rhodymenan, a linear soluble beta-1,3-beta
      1,4-xylan, was as the best substrate. Linear xylooligosaccharides were attacked
      exclusively at the first glycosidic linkage from the reducing end. The gene xyn4,
      encoding XYN IV, was also isolated. It showed clear homology with xylanases
      classified in glycoside hydrolase family 30, which also includes glucanases and
      mannanases. The xyn4 gene was expressed slightly when grown on xylose and
      xylitol, clearly on arabinose, arabitol, sophorose, xylobiose, xylan and
      cellulose, but not on glucose or sorbitol, resembling induction of other
      xylanolytic enzymes from T. reesei. A recombinant enzyme prepared in a Pichia
      pastoris expression system exhibited identical catalytic properties to the enzyme
      isolated from the T. reesei culture medium. The physiological role of this unique
      enzyme remains unknown, but it may involve liberation of xylose from the reducing
      end of branched oligosaccharides that are resistant toward beta-xylosidase and
      other types of endoxylanases. In terms of its catalytic properties, XYN IV
      differs from bacterial GH family 30 glucuronoxylanases that recognize 4-O-methyl
      D-glucuronic acid (MeGlcA) substituents as substrate specificity determinants.

PMID- 23167780
TI  - Efficacy of low- and high-dose trilostane treatment in dogs (< 5 kg) with
      pituitary-dependent hyperadrenocorticism.
AB  - BACKGROUND: Trilostane is commonly used to treat pituitary-dependent
      hyperadrenocorticism (PDH) in dogs. There are differing opinions regarding the
      dose and frequency of trilostane administration in dogs with PDH. OBJECTIVES: To
      compare the efficacy of 2 trilostane protocols in the treatment of dogs with PDH.
      ANIMALS: Sixteen client-owned dogs with PDH and a body weight <5 kg. METHODS:
      Prospective observational study. Group A (n=9; low-dose treatment group) received
      0.78 +/- 0.26 mg of trilostane/kg PO every 12 h and group B (n = 7; high-dose
      treatment group) 30 mg of trilostane/dog PO every 24 h. All of the dogs were
      reassessed at 2, 4, 8, 12, 16, and 24 weeks after the initiation of treatment.
      RESULTS: An improvement in both ACTH-stimulated serum cortisol concentrations and
      clinical signs occurred more slowly in group A than in group B; however, after 20
      weeks of treatment, 2/7 dog in group B had clinical signs and abnormal laboratory
      findings consistent with hypoadrenocorticism. At 24 weeks, an improvement in the
      clinical findings of all of the dogs in both groups was detected. CONCLUSIONS AND
      CLINICAL IMPORTANCE: In dogs with PDH, twice-daily administration of low-dose
      trilostane is an effective approach to the management of PDH. In addition, our
      results suggest fewer potential adverse effects if trilostane is administered
      twice daily in the lower dose.

PMID- 23167781
TI  - Effect of osteopontin on the initial adhesion of dental bacteria.
AB  - Bacterial biofilms are involved in numerous infections of the human body,
      including dental caries. While conventional therapy of biofilm diseases aims at
      eradication and mechanical removal of the biofilms, recent therapeutic approaches
      target the mechanisms of biofilm formation and bacterial adhesion in particular.
      The effect of bovine milk osteopontin, a highly phosphorylated whey protein, on
      adhesion of Streptococcus mitis, Streptococcus sanguinis, and Actinomyces
      naeslundii, three prominent colonizers in dental biofilms, to saliva-coated
      surfaces was investigated. While adhesion of A. naeslundii was not affected by
      osteopontin, a strong, dose-dependent reduction in the number of adhering S.
      mitis was shown. No difference in bacterial adhesion was observed for
      caseinoglycomacropeptide, another phosphorylated milk protein. Osteopontin did
      not affect bacterial viability, but changed bacterial surface hydrophobicity, and
      may be suggested to prevent the adhesins of S. mitis from interacting with their
      salivary receptors. The antiadhesive effect of osteopontin may be useful for
      caries prevention.

PMID- 23167782
TI  - A transduced living hyaline cartilage graft releasing transgenic stromal cell
      derived factor-1 inducing endogenous stem cell homing in vivo.
AB  - Stromal cell-derived factor-1 (SDF-1), also known as a homing factor, is a potent
      chemokine that activates and directs mobilization, migration, and retention of
      certain cell species via systemic circulation. The responding homing cells
      largely consist of activated stem cells, so that, in case of tissue lesions, such
      SDF-1-induced cell migration may execute recruitment of endogenous stem cells to
      perform autoreparation and compensatory regeneration in situ. In this study, a
      recombinant adenoviral vector carrying SDF-1 transgene was constructed and
      applied to transduce a novel scaffold-free living hyaline cartilage graft (SDF-t
      LhCG). As an engineered transgenic living tissue, SDF-t-LhCG is capable of
      continuously producing and releasing SDF-1 in vitro and in vivo. The in vitro
      trials were examined with ELISA, while the in vivo trials were subsequently
      performed via a subcutaneous implantation of SDF-t-LhCG in a nude mouse model,
      followed by series of biochemical and biological analyses. The results indicate
      that transgenic SDF-1 enhanced the presence of this chemokine in mouse's
      circulation system; in consequence, SDF-1-induced activation and recruitment of
      endogenous stem cells were also augmented in both peripheral blood and SDF-t-LhCG
      implant per se. These results were obtained via flow cytometry analyses on mouse
      blood samples and implanted SDF-t-LhCG samples, indicating an upregulation of the
      CXCR4(+)(SDF-1 receptor) cell population, accompanied by upregulation of the
      CD34(+), CD44(+), and Sca-1(+) cell populations as well as a downregulation of
      the CD11b(+) cell population. With the supply of SDF-1-recruited endogenous stem
      cells, enhanced chondrogenesis was observed in SDF-t-LhCG implants in situ.

PMID- 23167783
TI  - The effects of bromocriptine on VEGF, kidney function and ovarian
      hyperstimulation syndrome in in vitro fertilization patients: a pilot study.
AB  - The aim of this study was to evaluate the effects of bromocriptine on vascular
      endothelial growth factor (VEGF) levels in serum, kidney function and ovarian
      hyperstimulation syndrome in women undergoing in vitro fertilization. Twenty
      eight women were randomly divided into two groups and were administered daily
      oral capsules for 14 days, starting on the day of human chorionic gonadotropin
      (hCG) administration. Group A received 2.0 mg of folic acid, whereas Group B was
      given 2.5 mg of bromocriptine. Physical exams, pelvic ultrasounds and laboratory
      evaluations were performed on the day of hCG administration and again 7 days
      later. No differences in ovarian hyperstimulation syndrome, urine volume,
      creatinine clearance, urine sodium concentration or serum VEGF levels were found
      between the two groups. Thus, these results indicate that bromocriptine does not
      affect blood levels of VEGF, kidney function or the incidence of ovarian
      hyperstimulation syndrome in high-risk patients subjected to in vitro
      fertilization.

PMID- 23167784
TI  - Prevalence of CAM use by UK climacteric women: a systematic review of surveys.
AB  - AIMS: This systematic review is aimed at assessing surveys which monitor the
      prevalence of complementary and alternative medicine (CAM) use by climacteric
      women living in the UK. METHOD: Five databases were searched for English
      language, peer-reviewed surveys published between 1 January 2000 and 7 October
      2011. In addition, the bibliographies of key articles, relevant book chapters and
      our own departmental files were hand-searched. RESULTS: Three surveys were found
      and they included a total of 3742 climacteric women. All of these surveys were of
      poor methodological quality. The average prevalence of CAM use was 57.25%. Based
      on two surveys, 56% of women mentioned they were regular CAM users. The average
      perceived effectiveness of CAM was 72%. CONCLUSIONS: There is a paucity of high
      quality surveys monitoring the prevalence of CAM use by UK climacteric women. The
      available evidence suggests that the prevalence of CAM use amongst climacteric
      women is high. Due to the low methodological quality and paucity of the primary
      data, these results should be interpreted with caution.

PMID- 23167785
TI  - Edwardsiella piscicida sp. nov., a novel species pathogenic to fish.
AB  - AIMS: This study describes a novel species within the genus Edwardsiella based on
      phenotypic and genetic characterization of fish pathogenic Edwardsiella isolates
      previously identified as E. tarda. METHODS AND RESULTS: Phenotypic
      characterization, DNA-DNA hybridization and phylogenetic analysis of
      representative Edwardsiella isolates from fish previously identified as E. tarda
      were conducted and compared with E. tarda type strain (ATCC 15947(T)).
      Phenotypically, strains from fish grow with pin-point colonies producing slight
      beta-haemolysis under the colony. In contrast to the E. tarda type strain, fish
      strains did not [corrected] degrade beta-methyl-D-glucoside [corrected] (with the
      exception of NCIMB 2034), citric acid and L-proline. [corrected]. With the
      exception of strain ETK01, all fish strains were highly pathogenic to zebra fish,
      while ATCC 15947(T) and NCIMB 2034 were nonpathogenic. DNA-DNA hybridization
      (DDH) levels between representative fish isolates and the E. tarda type strain
      ranged from 15 to 43.6%, while NCIMB 2034 hybridised with the type strain at the
      level of 63.2%. DDH values between the various fish isolates ranged from 68.2 to
      93.9% defining a new and separate DNA hybridization group differing from the E.
      tarda type strain consistent with the findings of phylogenetic analysis, in which
      the fish isolates comprised a separate clade. CONCLUSIONS: Phenotypical and
      genetic characterizations demonstrated that Edwardsiella isolates from fish
      described in this study do not belong to the species E. tarda or any of the
      previously established taxa within the genus Edwardsiella. The fish related
      strains studied here (excluding NCIMB 2034) represent, therefore, a novel species
      within the genus Edwardsiella for which we propose the name Edwardsiella
      piscicida sp. nov, with strain ET883(T) (NCIMB 14824(T) = CCUG 62929) as the type
      strain. SIGNIFICANCE AND IMPACT OF THE STUDY: The current finding will improve
      the diagnosis, understanding of the epidemiology and in establishment of
      effective control measures against this serious fish pathogen.

PMID- 23167786
TI  - Tivantinib  in hepatocellular carcinoma.
AB  - INTRODUCTION: Tivantinib (ARQ 197) is a selective, oral MET receptor tyrosine
      kinase inhibitor with broad-spectrum antitumor activity as single agent and in
      combination in preclinical studies including several MET overexpressing cell
      lines. AREAS COVERED: This paper covers the preclinical data, the Phase I studies
      as monotherapy or in combination with sorafenib, and a Phase II study as second
      line systemic treatment in patients with advanced hepatocellular carcinoma (HCC).
      The analysis of MET expression as companion diagnostic and the safety profile of
      tivantinib in HCC are discussed. EXPERT OPINION: Tivantinib, a novel MET
      inhibitor with an ATP-independent binding mechanism, stabilizes the inactive
      conformation of the MET receptor tyrosine kinase, thus disrupting constitutive
      and ligand-mediated activation. MET overexpression was shown as a negative
      prognostic factor in HCC after sorafenib failure. Tivantinib demonstrated a
      nearly doubling of progression free and overall survival in the MET high group
      compared to placebo in a Phase II study in patients with advanced HCC as second
      line treatment. The activity of tivantinib in combination with sorafenib is also
      promising. Adverse events include hematological toxicity, asthenia and loss of
      appetite. The initially high incidence of neutropenia in patients with HCC lead
      to dose reduction from 360 mg b.i.d. to 240 mg b.i.d. Currently, a pivotal Phase
      III study in advanced, MET-high HCC after sorafenib failure is planned.

PMID- 23167787
TI  - Persistent hypoxia: where is the shunt?

PMID- 23167788
TI  - Systematic review and meta-analysis of the efficacy of sphingosine-1-phosphate
      (S1P) receptor agonist FTY720 (fingolimod) in animal models of stroke.
AB  - BACKGROUND AND PURPOSE: FTY720 (fingolimod) is a known sphingosine-1-phosphate
      (S1P) receptor agonist, which has been used in clinical trials for treating
      multiple sclerosis, renal transplantation, and decreasing reperfusion injury in
      heart, liver, and kidney. Most of these clinical trials have showed a positive
      effect. Especially, the trials of MS showed a reduction of relapse rate in FTY720
      treated patients. Now, some animal experiments indicated that FTY720 could be a
      new compound available treatment for stroke patients by exerting neuroprotection
      via S1P1 mediated antiapoptotic mechanisms. Whether it could be effective in
      animals is unclear, so we conducted a systematic review to make it clear.
      METHODS: We conducted a systematic review and meta-analysis of the efficacy of
      FTY720 in animal models of focal cerebral ischemia by electronic and manual
      searches of the literature. Data on study quality, FTY720 dose, time of
      administration, and outcome measured as infarct volume or functional deficit were
      extracted. Data from all studies were analyzed by means of a standardized mean
      difference meta-analysis. RESULTS: Of the 19 identified studies, 9 were included.
      Among all the included studies, 178 animals were calculated for infarct size and
      194 animals were assessed of neurological deficits. The methodological quality of
      the studies ranged from 2 to 10 according to a published 11-item quality scale.
      Of the nine studies selected, only one reported a negative result of FTY720. The
      result indicated that FTY720 reduced the infarct volume (SMD = -1.31, 95% CI 
      1.99 to -0.63) and improve the functional outcome (SMD = -1.61, 95% CI -2.17 to 
      1.05). CONCLUSIONS: The data we included supporting FTY720 was a candidate drug
      for stroke, but it should be considered with caution. More good quality
      experimental studies should be performed to evaluate the safety of FTY720 in the
      future. Whether FTY720 is effective in aged animals that mimicked human with
      comorbidities like diabetes and hypertension should also be deliberated.

PMID- 23167789
TI  - Midwall ejection fraction for assessing systolic performance of the hypertrophic
      left ventricle.
AB  - BACKGROUND: In patients with left ventricular hypertrophy (LVH), LV midwall
      fractional shortening (FS) is used as a measure of LV systolic performance that
      is more physiologically appropriate than conventional FS. For evaluation of LV
      volume and ejection fraction (EF), 2-dimensional (2D) echocardiography is more
      accurate than M-mode echocardiography. The purpose of this study was to assess
      systolic performance by midwall EF using 2D speckle tracking echocardiography
      (STE). METHODS: Sixty patients were enrolled in the study. Patients were divided
      into two groups with LVH (n = 30) and without LVH (control group, n = 30). LV
      systolic function was compared between the two groups and the relationships of
      left ventricular mass index (LVMI) with LV systolic parameters, including midwall
      EF, were investigated. RESULTS: Midwall EF in the LVH group was significantly
      lower than that in the control group (42.8+/-4.4% vs. 48.1+/-4.1%, p <0.0001).
      Midwall FS was also significantly lower in the LVH group (13.4+/-2.8% vs. 16.1+/
      1.5%, p <0.0001), but EF did not differ significantly between the two groups.
      There were significant correlations between midwall EF and LVMI (r=0.731, p
      <0.0001) and between midwall FS and LVMI (r=0.693, p <0.0001), with midwall EF
      having the higher correlation. CONCLUSIONS: These results show that midwall EF
      can be determined using 2D STE. Midwall EF can be used to monitor LV systolic
      dysfunction, which is not possible with conventional EF. Evaluation of midwall EF
      may allow assessment of new parameters of LV systolic function in patients with
      LV geometric variability.

PMID- 23167790
TI  - Daily exposure to cold phase-shifts the circadian clock of neonatal rats in vivo.
AB  - Maternal rhythms entrain the prenatal and neonatal circadian clock in the
      suprachiasmatic nucleus (SCN) before light entrainment is established. However,
      the responsible time cues for maternal entrainment are not identified. To examine
      the role of cyclic changes of ambient temperature in maternal entrainment, blind
      neonatal rats carrying a clock gene (Per2) bioluminescence reporter were exposed
      to either of three ambient temperatures (10, 20 or 30  degrees C) during 6-h
      maternal separation in the early light phase. Cold exposure was performed from
      postnatal day 1 (P1) to P5. On P6, the SCN was harvested and cultured for
      photometric monitoring of the circadian rhythm in Per2 expression. Here we
      demonstrate that the daily cold exposure phase-delayed the circadian Per2
      expression rhythms at P6 in a temperature-dependent manner. Exposure to 10 
      degrees C produced the largest phase-shift of 12.7 h, and exposure to 20 and 30 
      degrees C yielded moderate shifts of 4.1 and 4.5 h, respectively. There was no
      significant difference in the phase-shifts between the latter two temperatures,
      indicating that ambient temperature is not the sole factor for the phase-shift.
      Behavioral rhythms that developed after weaning reflected the phase-shift of
      clock gene expression rhythm in the SCN. These findings indicate that a daily
      exposure to an ambient temperature of 10  degrees C during the neonatal period is
      capable of resetting the circadian clock in the SCN, but other factors yet
      unidentified are also involved in maternal entrainment.

PMID- 23167792
TI  - Synthetic, natural and related compounds: new approach to chronic diseases
      studies.

PMID- 23167791
TI  - Predictors for health facility delivery in Busia district of Uganda: a cross
      sectional study.
AB  - BACKGROUND: Among the factors contributing to the high maternal morbidity and
      mortality in Uganda is the high proportion of pregnant women who do not deliver
      under supervision in health facilities. This study aimed to identify the
      independent predictors of health facility delivery in Busia a rural district in
      Uganda with a view of suggesting measures for remedial action. METHODS: In a
      cross sectional survey, 500 women who had a delivery in the past two years (from
      November 16 2005 to November 15 2007) were interviewed regarding place of
      delivery, demographic characteristics, reproductive history, attendance for
      antenatal care, accessibility of health services, preferred delivery positions,
      preference for disposal of placenta and mother's autonomy in decision making. In
      addition the household socio economic status was assessed. The independent
      predictors of health facility delivery were identified by comparing women who
      delivered in health facilities to those who did not, using bivariate and binary
      logistic regression analysis. RESULTS: Eight independent predictors that favoured
      delivery in a health facility include: being of high socio-economic status
      (adjusted odds ratio [AOR] 2.8 95% Confidence interval [95% CI]1.2-6.3), previous
      difficult delivery (AOR 4.2, 95% CI 3.0-8.0), parity less than four (AOR 2.9, 95%
      CI 1.6-5.6), preference of supine position for second stage of labour (AOR 5.9,
      95% CI 3.5-11.1) preferring health workers to dispose the placenta (AOR 12.1, 95%
      CI 4.3-34.1), not having difficulty with transport (AOR 2.0, 95% CI 1.2-3.5),
      being autonomous in decision to attend antenatal care (AOR 1.9, 95% CI 1.1-3.4)
      and depending on other people (e.g. spouse) in making a decision of where to
      deliver from (AOR 2.4, 95% CI 1.4-4.6). A model with these 8 variables had an
      overall correct classification of 81.4% (chi square = 230.3, P < 0.001).
      CONCLUSIONS: These data suggest that in order to increase health facility
      deliveries there is need for reaching women of low social economic status and of
      higher parity with suitable interventions aimed at reducing barriers that make
      women less likely to deliver in health units such as ensuring availability of
      transport and involving spouses in the birth plan.

PMID- 23167793
TI  - Docking, synthesis and anti-diabetic activity of novel sulfonylhydrazone
      derivatives designed as PPAR-gamma agonists.
AB  - Diabetes is a metabolic disorder characterized by hyperglycemia. When not
      properly controlled, complications include neuropathy, coronary artery disease,
      and renal failure. Several drugs are approved for diabetes treatment; however
      their use is associated with side effects and lack of efficacy in attenuating the
      development of long-term complications. This work describes the virtual screening
      and synthesis of a novel series of sulfonylhydrazone derivatives designed as
      peroxisome proliferator-activated receptor gamma (PPARgamma) agonists and
      investigation of the analogs for hypoglycemic activity in a murine model of
      diabetes. Docking studies identified LASSBio-331 (5) as having theoretical
      affinity for PPARgamma similar to the prototype (S)-rosiglitazone. Several
      structural modifications were proposed for the structure of LASSBio-331,
      resulting in the synthesis of five novel compounds, which showed experimental
      affinity for PPARgamma. Among these new compounds, LASSBio-1471 (15) had the best
      theoretical binding energy for PPARgamma and was selected for testing in STZ
      induced diabetes. Four weeks after single intravenous injection of STZ (60
      mg/kg), Wistar rats were treated with vehicle (DMSO) or LASSBio-1471 (20 mg/kg,
      i.p.) for 7 days. The blood glucose levels of rats treated with LASSBio-1471 were
      reduced from 548.4 +/- 26.0 mg/dL before treatment to 259.6 +/- 73.1 mg/dL (P <
      0.05). Paw withdrawal threshold was significantly reduced in diabetic rats and
      was restored from 21.9 +/- 1.7 g to 36.7 +/- 1.2 g after 7 days of treatment with
      LASSBio-1471 (P < 0.05). Thus, the novel sulfonylhydrazone derivative is a
      PPARgamma ligand that is effective for treatment of diabetic neuropathy in STZ
      injected rats.

PMID- 23167794
TI  - Acylhydrazones contribute to serum glucose homeostasis through dual physiological
      targets.
AB  - In this study the in vivo and in vitro antidiabetic effects of four acylhydrazone
      derivatives were investigated in rats. The secretagogue action, oral glucose
      tolerance, insulinogenic index and mechanism of action of these acylhydrazones in
      relation to calcium uptake in pancreatic islets were studied. Also, the
      insulinomimetic effect on glycemia in diabetic rats was verified. Of the
      acylhydrazones studied, 1 and 4 were able to increase glucose tolerance in an
      acute time-course. A powerful secretagogue effect was exhibited by 1 and
      glibenclamide with an insulinogenic index around 3.9 and 1.3-fold higher than
      that of the hyperglycemic group, respectively. Moreover, an acute and dose
      dependent effect of glibenclamide and 1 on calcium uptake in pancreatic islets
      was observed. The rapid stimulatory effect of 1 on calcium uptake seems to be
      mediated, at least in part, by ATP-dependent K+ channels (K+-ATP) since the
      stimulatory effect of 1 was similar to that observed for glibenclamide but was
      not potentiated by sulphonylurea. Furthermore, both extracellular and calcium
      from stocks mediate the signal transduction of stimulatory effect of 1 on calcium
      uptake which may contribute to insulin secretion. In addition, the
      insulinomimetic effect of 1 was evidenced through the level of serum glucose
      lowering in alloxan-induced diabetic rats. Also, 1 induced a significant increase
      in glycogen content in vivo and glucose uptake in soleus muscle in vitro. The
      results of this study indicate dual physiological targets for the acylhydrazone
      1, i.e., pancreatic islets and skeletal muscle, as a result of insulin
      secretagogue and insulinomimetic action.

PMID- 23167795
TI  - Estrogen receptor 1 agonist PPT stimulates Slc2a4 gene expression and improves
      insulin-induced glucose uptake in adipocytes.
AB  - Type 2 diabetes mellitus is characterized by disruption in glycemic homeostasis,
      involving impaired insulin-induced glucose disposal. For that, reduced glucose
      transporter GLUT4, encoded by Slc2a4 gene, plays a fundamental role. Conversely,
      increase in Slc2a4/GLUT4 expression improves glycemic homeostasis. Recent studies
      have proposed that estradiol is able to modulate Slc2a4 expression, according to
      distinct effects upon estrogen receptors ESR1/ESR2. We hypothesize that ESR1
      agonist effect could stimulate Slc2a4 expression; thus, increasing cellular
      glucose disposal, which could be beneficial to glycemic control. Differentiated
      3T3-L1 adipocytes were treated (24 hours) with selective ESR1- agonist PPT 1,3,5
      tris(4-hydroxyphenyl)-4-propyl-1H-pyrazole, selective ESR1-antagonist MPP 1,3
      Bis(4- hydroxyphenyl)-4-methyl-5-[4-(2-piperidinylethoxy)phenol]-1H-pyrazole
      dihydrochloride, and selective ESR2 agonist DPN 2,3-bis(4-Hydroxyphenyl)
      propionitrile, with/without 17beta-estradiol (E2). We analyzed Slc2a4 mRNA (real
      time PCR) and GLUT4 protein (Western blotting) expression, transcriptional
      activity of the Slc2a4 repressor Nuclear Factor- kappaB (NF-kappaB)
      (electrophoretic mobility shift assay), and cellular glucose disposal (2-deoxi-D
      [(3)H]glucose uptake, 2-DG). ESR1-agonist PPT enhanced Slc2a4/GLUT4 expression
      (~30%) in the absence or presence of 0.1 and 10 nmol/L E2, and decreased the NF
      kappaB binding activity (~50%). Conversely, ESR1-antagonist MPP, together with
      E2, decreased Slc2a4/GLUT4 expression (20-40%) and increased NF-kappaB binding
      activity (~30%). Furthermore, treatment with ESR2- agonist DPN decreased
      Slc2a4/GLUT4 expression (20-50%). 2-DG uptake was modulated in parallel to that
      observed in GLUT4 protein. The present results reveal that ESR1 activity
      enhances, whereas ESR2 activity represses, Slc2a4/GLUT4 expression. These effects
      are partially mediated by NF-kappaB, and allow parallel changes in adipocyte
      glucose disposal. Furthermore, the data provide evidences that ESR1-agonist PPT,
      as a Slc2a4/GLUT4 enhancer, can be a promising coadjuvant drug for diabetes
      mellitus therapy.

PMID- 23167796
TI  - The central nervous system as a promising target to treat diabetes mellitus.
AB  - Most of the drugs available to treat type 2 diabetes mellitus (T2DM) act either
      in the pancreas by increasing insulin secretion or in tissues such as the liver
      or muscle by improving insulin sensitivity. However, recent studies have shown
      that the brain also plays a critical role in the regulation of glucose
      homeostasis. For example, central leptin administration reduces hyperglycemia and
      improves the survival of mice with type 1 diabetes mellitus (T1DM). In addition,
      several pieces of evidence show that the brain can control the insulin
      sensitivity in different tissues and the pancreatic secretion of insulin and
      glucagon. Therefore, the brain emerges as a promising new target of drugs aiming
      to treat both T1DM and T2DM. An exciting finding is that there is a partial
      overlap between neuronal populations that regulate energy balance and glucose
      homeostasis. Therefore, obesity and T2DM may have similar origins that are
      related to dysfunctions in the central nervous system. Likewise, future drugs
      that target the brain to treat T2DM may have beneficial effects in reducing body
      weight, and vice versa. In this review, the recent data showing how the brain is
      able to have an important regulatory effect over blood glucose levels as well as
      the possible neuronal circuitries involved in the control of glucose homeostasis
      will be summarized. The opportunities and challenges of using synthetic drugs or
      natural compounds that act in the central nervous system to treat diabetes
      mellitus will also be discussed.

PMID- 23167797
TI  - Equinatoxin II potentiates temozolomide- and etoposide-induced glioblastoma cell
      death.
AB  - Glioblastoma (GBM) is considered incurable due to its resistance to current
      cancer treatments. So far, all clinically available alternatives for treating GBM
      are limited, evoking the development of novel treatment strategies that can more
      effectively manage these tumors. Extensive effort is being dedicated to
      characterize the molecular basis of GBM resistance to chemotherapy and to explore
      novel therapeutic procedures that may improve overall survival. Cytolysins are
      toxins that form pores in target cell membranes, modifying ion homeostasis and
      leading to cell death. These pore-forming toxins might be used, therefore, to
      enhance the efficiency of conventional chemotherapeutic drugs, facilitating their
      entrance into the cell. In this study, we show that a non-cytotoxic concentration
      of equinatoxin II (EqTx-II), a pore-forming toxin from the sea anemone Actinia
      equina, potentiates the cytotoxicity induced by temozolomide (TMZ), a first-line
      GBM treatment, and by etoposide (VP-16), a second- or third-line GBM treatment.
      We also suggest that this effect is selective to GBM cells and occurs via
      PI3K/Akt pathway inhibition. Finally, Magnetic resonance imaging (MRI) revealed
      that a non-cytotoxic concentration of EqTx-II potentiates the VP-16-induced
      inhibition of GBM growth in vivo. These combined therapies constitute a new and
      potentially valuable tool for GBM treatment, leading to the requirement of lower
      concentrations of chemotherapeutic drugs and possibly reducing, therefore, the
      adverse effects of chemotherapy.

PMID- 23167798
TI  - Biological evaluation of 3-acyl-2-arylamino-1,4-naphthoquinones as inhibitors of
      Hsp90 chaperoning function.
AB  - Hsp90 is a chaperone that plays a key function in cancer cells by stabilizing
      proteins responsible of cell growth and survival. Disruption of the Hsp90
      chaperone machinery leads to the proteasomal degradation of its client proteins.
      Hsp90 appears then as an attractive target for the development of new anticancer
      molecules. We have shown that ascorbate- driven menadione-redox cycling inhibits
      Hsp90 activity by provoking an N-terminal cleavage of the protein, inducing the
      degradation of several of its client proteins. Since the mechanism involves an
      oxidative stress, we explored the effect of a series of diverse donor-acceptor 3
      acyl-2-phenylamino 1,4-naphthoquinones on Hsp90 integrity, in the presence of
      ascorbate. Results show that quinone-derivatives that bear two electroactive
      groups (namely quinone and nitro) exhibit the highest inhibitory activity (Hsp90
      cleavage and cell death). The biological activity of the series mainly relies on
      their redox capacity and their lipophilicity, which both modulate the ability of
      these compounds to induce a cytotoxic effect in K562 cells. As observed with
      other redox cycling quinones, the protein cleavage is blocked in the presence of
      N-terminal Hsp90 inhibitors suggesting that the availability or occupancy of
      nucleotide binding site in the N-terminal pocket of Hsp90 plays a critical role.
      In addition the survival of cancer cells and their metabolic and redox
      homeostasis were strongly impaired by the presence of ascorbate. Since these
      effects were similar to that obtained by ascorbate/menadione and they were
      blocked by the antioxidant N-acetylcyteine (NAC), it appears that oxidative
      stress is a major component of this cytotoxicity.

PMID- 23167799
TI  - Effects of natural compounds on Xenopus embryogenesis: a potential read out for
      functional drug discovery targeting Wnt/beta-catenin signaling.
AB  - Maternal Wnt/beta-Catenin signaling is essential to establish dorsal-specific
      gene expression required for axial patterning in Xenopus. Deregulation of this
      pathway causes axis phenotypes in frog embryos. In adult life, mutations in the
      Wnt pathway components are associated with many diseases, such as polyposis coli;
      osteoporosis-pseudoglioma syndrome (OPPG); skeletal dysplasia; neural tube
      defects, cancer and many others. Thus, a better understanding of Wnt/beta-catenin
      signaling will have great and significant impact on Biology and Medicine. In this
      aspect, natural compounds are potential targets as novel molecules that could
      modulate the Wnt pathway. For instance, flavonoids are a large group of natural
      compounds found in plants that modulate important cellular and molecular
      mechanisms related to diseases, but the specific in vivo mechanism of action of
      most flavonoids remain unknown. In this way, Xenopus embryos may provide an
      efficient model, since it is frequently used to test and identify the role of
      molecules that affect Wnt/beta-catenin signaling. Here, we describe a combination
      of approaches to outline and characterize the role of two flavonoids, quercetin
      and rutin, on Wnt/beta-catenin signaling, using Xenopus embryos as an
      experimental model. Our data support that quercetin is potential in vivo
      modulator of canonical Wnt signaling and that this effect might depend on the
      structure of this molecule, as we did not observe any effect with rutin
      treatment, a flavonol structurally-related to quercetin. This model is useful to
      analyze effects of quercetin and other flavonoids in vivo and to provide further
      understanding of how natural compounds can modulate signaling pathways, using
      Xenopus embryos as a fast and efficient reading of in vivo effects of those
      compounds.

PMID- 23167800
TI  - Gold(I)-catalyzed Claisen rearrangement of allenyl vinyl ethers: missing
      transition states revealed through evolution of aromaticity, Au(I) as an
      oxophilic Lewis acid, and lower energy barriers from a high energy complex.
AB  - Curtin-Hammett analysis of four alternative mechanisms of the gold(I)-catalyzed
      [3,3] sigmatropic rearrangement of allenyl vinyl ethers by density functional
      theory calculations reveals that the lowest energy pathway (cation-accelerated
      oxonia Claisen rearrangement) originates from the second most stable of the four
      Au(I)-substrate complexes in which gold(I) coordinates to the lone pair of
      oxygen. This pathway proceeds via a dissociative transition state where the C-O
      bond cleavage precedes C1-C6 bond formation. The alternative Au(I) coordination
      at the vinyl pi-system produces a more stable but less reactive complex. The two
      least stable modes of coordination at the allenyl pi-system display reactivity
      that is intermediate between that of the Au(I)-oxygen and the Au(I)-vinyl ether
      complexes. The unusual electronic features of the four potential energy surfaces
      (PESs) associated with the four possible mechanisms were probed with intrinsic
      reaction coordinate calculations in conjunction with nucleus independent chemical
      shift (NICS(0)) evaluation of aromaticity of the transient structures. The
      development of aromatic character along the "6-endo" reaction path is modulated
      via Au-complexation to the extent where both the cyclic intermediate and the
      associated fragmentation transition state do not correspond to stationary points
      at the reaction potential energy surface. This analysis explains why the
      calculated PES for cyclization promoted by coordination of gold(I) to allenyl
      moiety lacks a discernible intermediate despite proceeding via a highly
      asynchronous transition state with characteristics of a stepwise "cyclization
      mediated" process. Although reaction barriers can be strongly modified by aryl
      substituents of varying electronic demand, direct comparison of experimental and
      computational substituent effects is complicated by formation of Au-complexes
      with the Lewis-basic sites of the substrates.

PMID- 23167801
TI  - Trifluoromethanesulfonamides and related compounds.

PMID- 23167802
TI  - Recurrence risk of congenital malformations in infants exposed to antiepileptic
      drugs in utero.
AB  - PURPOSE: Use of antiepileptic drugs in pregnancy is associated with congenital
      malformations and developmental delay. Previous studies have suggested that women
      who have had one child with a congenital malformation are at increased risk of
      having other children with malformations. We sought to confirm the magnitude of
      risk in a large cohort drawn from the United Kingdom Epilepsy and Pregnancy
      Register. METHODS: The United Kingdom Epilepsy and Pregnancy Register is a
      prospective, observational registration and follow-up study set up to determine
      the relative safety of antiepileptic drugs in pregnancy. We have extracted data
      for those women who prospectively registered more than one pregnancy and
      calculated the recurrence risks for fetal malformations. KEY FINDINGS: Outcome
      data were available for 1,534 pregnancies born to 719 mothers. For women whose
      first child had a congenital malformation there was a 16.8% risk of having
      another child with a congenital malformation, compared with 9.8% for women whose
      first child did not have a malformation (relative risk 1.73, 95% confidence
      interval [CI] 1.01-2.96). The risk for recurrence was 50% for women who had had
      two previous children with a congenital malformation. There was a trend toward a
      higher risk for recurrent malformations in pregnancies exposed to valproate
      (21.9%, relative risk 1.47, 95% CI 0.68-3.20) and topiramate (50%, relative risk
      4.50, 95% CI 0.97-20.82), but not for other drugs such as carbamazepine and
      lamotrigine. Recurrence risks were also higher for pregnancies exposed to
      polytherapy regimens and for those where the dose of antiepileptic drug treatment
      had been increased after the first pregnancy. SIGNIFICANCE: Women who have had a
      child with a malformation are at increased risk of having other children with
      malformations. This is in keeping with previous reports that have suggested that
      genetic influences may be one of the factors determining the teratogenic risk of
      antiepileptic drugs.

PMID- 23167803
TI  - Added value of real time three-dimensional echocardiography in the diagnosis of
      an apical right ventricular metastasis from malignant melanoma.
AB  - In a man presenting to the emergency room with dyspnea and atypical chest pain
      irradiated among the scapulae, with new-onset diffuse negative T-waves on the
      ECG, the first clinical and diagnostic hypothesis was pulmonary embolism (PE).
      However, computed tomography (CT) performed in emergency was negative for PE,
      showing instead a marked defect in right ventricle (RV) filling. For this reason,
      echocardiography was performed to better investigate the nature of the space
      occupying lesion, and several echocardiographic modalities were used (two
      dimensional transthoracic and transesophageal echocardiography and three
      dimensional [3D] transthoracic echocardiography). They revealed the presence of a
      mass attached to the apex of the RV, partially obstructing the inflow and outflow
      tracts. Cardiac magnetic resonance imaging was also performed, confirming the
      findings of 3D echocardiography. After that, several other diagnostic imaging
      techniques were used for disease staging, since the patient had a history of
      surgical excision of a malignant melanoma of the skin several years before. Whole
      body CT, soft tissue echography and positron emission tomography revealed the
      widespread diffusion of the primary tumor to distant organs. For this reason, we
      suspected that the RV mass could also be an intracardiac metastasis from
      malignant melanoma, and did not perform biopsy given the bad clinical conditions
      and the worse prognosis of the patient. However, he was entered in an
      experimental therapeutic protocol with Vemurafenib because he showed B-RAF gene
      mutation at molecular gene analysis.

PMID- 23167804
TI  - Dynamic and galvanic stability of stretchable supercapacitors.
AB  - Stretchable electronics are emerging as a new technological advancement, since
      they can be reversibly stretched while maintaining functionality. To power
      stretchable electronics, rechargeable and stretchable energy storage devices
      become a necessity. Here, we demonstrate a facile and scalable fabrication of
      full stretchable supercapacitor, using buckled single-walled carbon nanotube
      macrofilms as the electrodes, an electrospun membrane of elastomeric polyurethane
      as the separator, and an organic electrolyte. We examine the electrochemical
      performance of the fully stretchable supercapacitors under dynamic
      stretching/releasing modes in different stretching strain rates, which reveal the
      true performance of the stretchable cells, compared to the conventional method of
      testing the cells under a statically stretched state. In addition, the self
      discharge of the supercapacitor and the electrochemical behavior under bending
      mode are also examined. The stretchable supercapacitors show excellent cyclic
      stability under electrochemical charge/discharge during in situ dynamic
      stretching/releasing.

PMID- 23167805
TI  - Impact of the transobturator tape procedure on sexual function in women with
      stress urinary incontinence.
AB  - AIM: Stress urinary incontinence (SUI) is a serious problem in women who have
      delivered vaginally, and causes some sexual dysfunction. The transobturator tape
      (TOT) procedure is one of the most common methods for the treatment of SUI. In
      the present study, we investigated the effect of the TOT procedure on sexual
      function in women. MATERIAL AND METHODS: From June 2008 to March 2011, 117
      patients underwent the TOT procedure for SUI in our clinic. Ninety-six sexually
      active women participated in the study and the mean age was 49.2 (29-61) years.
      Before and 6 months after surgery, the patients' sexual desire, arousal,
      lubrication, orgasm, satisfaction and pain during sexual intercourse and sexual
      functions were all evaluated with the Female Sexual Function Index questionnaire.
      The results were compared statistically using the Wilcoxon test. RESULTS: The
      cure rate of the TOT procedure for SUI was 87%. Of the 96 women who were sexually
      active, 35 (36%) experienced urinary loss during sexual activity. Thirty-three
      (95%) of these patients were cured after surgery completely. Female Sexual
      Function Index scores for desire, arousal, lubrication, orgasm and in total
      increased slightly after surgery but none of these improvements reached a
      statistically significant level. However, statistically significant improvement
      was determined for satisfaction and pain after surgery (P < 0.05). CONCLUSION:
      SUI causes some problems affecting quality of life, including sexual dysfunction.
      After the TOT procedure, significant improvement was determined in sexual
      function affected by SUI.

PMID- 23167806
TI  - Chronic administration of infliximab (TNF-alpha inhibitor) decreases depression
      and anxiety-like behaviour in rat model of chronic mild stress.
AB  - Pro-inflammatory cytokines have been proposed to be associated with the
      pathogenesis of depression. Consistent with this notion, several clinical
      observations have suggested the antidepressant efficacy of TNF-alpha inhibitors
      in patients with chronic inflammatory diseases. In this study, we evaluated the
      antidepressant and anxiolytic effects of chronic TNF-alpha inhibitor (infliximab,
      5 mg/kg, i.p., weekly) administration in the chronic mild stress (CMS) model of
      depression. Rats were divided into three groups: saline-control (no stress),
      saline-CMS, and infliximab-CMS. Rats in the latter two groups were exposed to CMS
      for 8 weeks. Saline (former two groups) or infliximab was injected weekly during
      this period. After CMS, total locomotor activity, anxiety-like behaviour and
      depression-like behaviours were evaluated using automated locomotor activity
      cage, elevated plus maze (EPM), and sucrose preference (SPT) and forced swimming
      (FS) tests, respectively. As expected, the saline-CMS group exhibited higher
      depression-like behaviours in FS and SPT tests compared with the saline-control
      group. There were no differences between these two groups in terms of the anxiety
      like behaviour or total locomotor activity. Infliximab reduced the depression
      like behaviour of CMS rats compared with saline-CMS group, and anxiety-like
      behaviour of CMS rats compared with saline-CMS and saline-control groups. Our
      findings suggest that chronic and systemic TNF-alpha inhibition reduced
      depression and anxiety-like behaviour in the CMS model of depression in rats.

PMID- 23167807
TI  - Prolactin insufficiency but normal thyroid hormone levels after cranial
      radiotherapy in long-term survivors of childhood leukaemia.
AB  - BACKGROUND: Acute lymphoblastic leukaemia (ALL) patients treated with cranial
      radiotherapy (CRT) have an increased risk of GH deficiency (GHD). Little is known
      about insufficiencies of prolactin (PRL) and TSH, but also lactation failure has
      been reported in this population. OBJECTIVE: To study the long-term outcome of
      CRT on PRL and thyroid hormone levels in GHD ALL patients and the prevalence of
      lactation failure. DESIGN: Case-control study. PATIENTS: We examined 40 GHD and 4
      GH insufficient ALL patients, in median 20 years (range: 8-27) after ALL
      diagnosis and 44 matched population controls. MEASUREMENTS: PRL secretion (area
      under the curve; AUC) after GHRH-arginine test in all patients and matched
      controls, and PRL and TSH AUC after a TRH-test in 13 patients and 13 controls.
      And basal PRL and thyroid hormone levels after 5 years with GH therapy and 8
      years without GH therapy. RESULTS: Compared with controls, ALL patients had
      significantly lower basal and AUC PRL after GHRH-Arginine (P = 0.03, P = 0.02),
      and AUC PRL after TRH (P = 0.001). After 5 and 8 years, PRL levels decreased
      further (P = 0.01, P = 0.03), but thyroid hormones remained normal at baseline
      and at follow-up. PRL insufficiency was significantly associated with increased
      levels of BMI and insulin. Six out of seven pregnant ALL women reported lactation
      failure. CONCLUSIONS: Long-term ALL survivors treated with CRT have GHD and PRL
      insufficiency, and a high prevalence of lactation failure, but thyroid hormones
      remained normal. PRL insufficiency was associated with cardiovascular risk.

PMID- 23167808
TI  - Adhesion of endothelial cells and endothelial progenitor cells on peptide-linked
      polymers in shear flow.
AB  - The initial adhesion of human umbilical vein endothelial cells (HUVECs), cord
      blood endothelial colony-forming cells (ECFCs), and human blood outgrowth
      endothelial cells (HBOECs) was studied under radial flow conditions. The surface
      of a variable shear-rate device was either coated with polymer films or covered
      by synthetic fibers. Spin-coating was applied to produce smooth polymer films,
      while fibrous scaffolds were generated by electrospinning. The polymer was
      composed of hexyl methacrylate, methyl methacrylate, poly(ethylene glycol)
      methacrylate (PEGMA), and CGRGDS peptide. The peptide was incorporated into the
      polymer system by coupling to an acrylate-PEG-N-hydroxysuccinimide comonomer. A
      shear-rate-dependent increase of the attached cells with time was observed with
      all cell types. The adhesion of ECs increased on RGD-linked polymer surfaces
      compared to polymers without adhesive peptides. The number of attached ECFCs and
      HBOECs are significantly higher than that of HUVECs within the entire shear-rate
      range and surfaces examined, especially on RGD-linked polymers at low shear
      rates. Their superior adhesion ability of endothelial progenitor cells under flow
      conditions suggests they are a promising source for in vivo seeding of vascular
      grafts and shows the potential to be used for self-endothelialized implants.

PMID- 23167809
TI  - CD117-CD15 in acute myeloid leukemia: no role as LAIP in the study of minimal
      residual disease.

PMID- 23167810
TI  - A search to identify genetic risk factors for endometriosis.
AB  - PROBLEM: To search for molecular markers of endometriosis the following
      polymorphisms: p53 codon 72 Pro (apoptosis), TNF alpha-308 (inflammation), VEGF
      1164AA (angiogenesis), and SOD2 (oxidative stress) were investigated. METHOD OF
      STUDY: Forty-two women-24 with surgically proven endometriosis and 18 with no
      endometriosis found at the time of laparoscopy-had buccal swabs taken for DNA
      analyses of 4 gene polymorphisms including p53codon72, TNF-308 G/A, VEGF-1154G/A,
      SOD Ala16Val DNA. The frequencies of genotypes and alleles of these polymorphisms
      were compared between women with and without endometriosis. RESULTS: No specific
      gene mutation differences for the four genes tested nor differences in the
      frequencies of heterozygous and homozygous mutations were found between patients
      with endometriosis and controls. In addition, no differences in allelic
      frequencies of the four genetic polymorphisms were observed between patients with
      endometriosis and control. CONCLUSION: Endometriosis is not associated with gene
      mutations for p53codon72, TNF-308 G/A, VEGF-1154G/A, SOD Ala16Val.

PMID- 23167811
TI  - A role for mitochondria in gestational diabetes mellitus?
AB  - Mitochondrial activity is critical for maintenance of correct glucose homeostasis
      and alteration in mitochondrial content or function may progressively lead to the
      development of insulin resistance. Evidence on the possible role of mitochondria
      in the pathogenesis of gestational diabetes mellitus (GDM) is conversely scanty
      and inconsistent. The aim was to evaluated mitochondrial DNA (mtDNA) content in
      peripheral blood of pregnant women with GDM. We selected 25 pregnant women
      affected by GDM and 50 controls with physiological pregnancies. A blood sample
      was collected at 32-36 weeks' gestation, stored and thawed simultaneously. The
      mtDNA content was determined utilizing a quantitative real-time polymerase chain
      reaction by the Taqman method, using a genomic control and a target gene. Results
      are expressed as copy number per nuclear DNA. The median (interquartile range)
      mtDNA content in GDM and controls was 122 (107-198) and 170 (129-196),
      respectively (p = 0.039). The mtDNA content was also correlated to GDM treatment,
      self-blood glucose monitoring and newborns' weight, but these analyses failed to
      document any statistically significant association. Attenuated mitochondrial
      function may play a role in the development of GDM. Further experiments are
      required to definitely clarify whether this defect represents a primary event in
      the pathogenesis of the disease.

PMID- 23167812
TI  - 8,8-dialkyldihydroberberines with potent antiprotozoal activity.
AB  - Semisynthetic 8,8-dialkyldihydroberberines (8,8-DDBs) were found to possess mid-
      to low-nanomolar potency against Plasmodium falciparum blood-stage parasites,
      Leishmania donovani intracellular amastigotes, and Trypanosoma brucei brucei
      bloodstream forms. For example, 8,8-diethyldihydroberberine chloride (5b)
      exhibited in vitro IC50 values of 77, 100, and 5.3 nM against these three
      parasites, respectively. In turn, two 8,8-dialkylcanadines, obtained by reduction
      of the corresponding 8,8-DDBs, were much less potent against these parasites in
      vitro. While the natural product berberine is a weak DNA binder, the 8,8-DDBs
      displayed no affinity for DNA, as assessed by changes in the melting temperature
      of poly(dA.dT) DNA. Selected 8,8-DDBs showed efficacy in mouse models of visceral
      leishmaniasis and African trypanosomiasis, with 8,8-dimethyldihydroberberine
      chloride (5a) reducing liver parasitemia by 46% in L. donovani-infected BALB/c
      mice when given at an intraperitoneal dose of 10 mg/kg/day for five days. The 8,8
      DDBs may thus serve as leads for discovering new antimalarial, antileishmanial,
      and antitrypanosomal drug candidates.

PMID- 23167814
TI  - Exaggerated NT-proBNP production in patients with hematologic malignancies: a
      case series.
AB  - (c)2011 Wiley Periodicals Inc. Extremely elevated serum brain natriuretic peptide
      (BNP) in cancer patients is a poorly understood phenomenon. The authors report
      three cases of patients with hematologic malignancies and serial N-terminal pro
      BNP (NT-proBNP) measurements with values in the range of tens to hundred
      thousands pg/mL. Through matching NT-proBNP results with clinical, laboratory,
      echocardiographic and radiologic data, the authors found that these patients
      demonstrated exaggerated responses to fluid overload. Patients with hematologic
      malignancies may have higher than expected values of NT-proBNP in response to
      hypervolemic states. The authors hypothesize that this may be related to possible
      infiltration of the myocardium by substances produced in the setting of these
      diseases or due to proteins interfering with the assay.Congest Heart Fail.

PMID- 23167815
TI  - Hyperoxaluria and systemic oxalosis: an update on current therapy and future
      directions.
AB  - INTRODUCTION: The primary hyperoxalurias (PH) are rare, but underdiagnosed
      disorders where the loss of enzymatic activity in key compounds of glyoxylate
      metabolism results in excessive endogenous oxalate generation. Clinically, they
      are characterized by recurrent urolithiasis and/or nephrocalcinosis. PH type I is
      the most frequent and most devastating subtype often leading to early end-stage
      renal failure. AREAS COVERED: Profound overview of clinical, diagnostic, and
      currently available treatment options with a focus on PH I at different stages of
      the disease. Discussion of future therapeutic avenues including pharmacological
      chaperones (small molecules rescuing protein function), gene therapy with safer
      adenoviral vectors, and potential application of cell-based transplantation
      strategies is provided. EXPERT OPINION: Due to lack of familiarity with PH and
      its heterogeneous clinical expression, diagnosis is often delayed until advanced
      disease is present, a condition, requiring intensive hemodialysis and timely
      transplantation. Achieving the most beneficial outcome largely depends on the
      knowledge of the clinical spectrum, early diagnosis, and initiation of treatment
      before renal failure ensues. A number of preconditions required for substantial
      improvement in the care of orphan disease like PH have now been achieved or soon
      will come within reach, so new treatment options can be expected in the near
      future.

PMID- 23167816
TI  - Chip-based nanostructured sensors enable accurate identification and
      classification of circulating tumor cells in prostate cancer patient blood
      samples.
AB  - The identification and analysis of circulating tumor cells (CTCs) is an important
      goal for the development of noninvasive cancer diagnosis. Here we describe a chip
      based method using nanostructured microelectrodes and electrochemical readout
      that confirms the identity of isolated CTCs and successfully interrogates them
      for specific biomarkers. We successfully analyze and classify prostate tumor
      cells, first in cultured cells, and ultimately in a pilot study involving blood
      samples from 16 prostate cancer patients as well as additional healthy controls.
      In all cases, and for all biomarkers investigated, the novel chip-based assay
      produced results that agreed with polymerase chain reaction (PCR). The approach
      developed has a simple workflow and scalable multiplexing, which makes it ideal
      for further studies of CTC biomarkers.

PMID- 23167813
TI  - Post-translation modification in Archaea: lessons from Haloferax volcanii and
      other haloarchaea.
AB  - As an ever-growing number of genome sequences appear, it is becoming increasingly
      clear that factors other than genome sequence impart complexity to the proteome.
      Of the various sources of proteomic variability, post-translational modifications
      (PTMs) most greatly serve to expand the variety of proteins found in the cell.
      Likewise, modulating the rates at which different proteins are degraded also
      results in a constantly changing cellular protein profile. While both strategies
      for generating proteomic diversity are adopted by organisms across evolution, the
      responsible pathways and enzymes in Archaea are often less well described than
      are their eukaryotic and bacterial counterparts. Studies on halophilic archaea,
      in particular Haloferax volcanii, originally isolated from the Dead Sea, are
      helping to fill the void. In this review, recent developments concerning PTMs and
      protein degradation in the haloarchaea are discussed.

PMID- 23167818
TI  - Growth, acid production and bacteriocin production by probiotic candidates under
      simulated colonic conditions.
AB  - AIMS: The aim of this study is to evaluate the capacity of three bacteriocin
      producers, namely Lactococcus lactis subsp. lactis biovar diacetylactis UL719
      (nisin Z producer), L. lactis ATCC 11454 (nisin A producer) and Pediococcus
      acidilactici UL5 (pediocin PA-1 producer), and to grow and produce their active
      bacteriocins in Macfarlane broth, which mimics the nutrient composition
      encountered in the human large intestine. METHODS AND RESULTS: The three
      bacteriocin-producing strains were grown in Macfarlane broth and in De Man-Rogosa
      Sharpe (MRS) broth. For each strain, the bacterial count, pH drop and production
      of organic acids and bacteriocins were measured for different period of time. The
      ability of the probiotic candidates to inhibit Listeria ivanovii HPB 28 in co
      culture in Macfarlane broth was also examined. Lactococcus lactis subsp. lactis
      biovar diacetylactis UL719, L. lactis ATCC 11454 and Ped. acidilactici UL5 were
      able to grow and produce their bacteriocins in MRS broth and in Macfarlane broth.
      Each of the three candidates inhibited L. ivanovii HPB 28, and this inhibition
      activity was correlated with bacteriocin production. The role of bacteriocin
      production in the inhibition of L. ivanovii in Macfarlane broth was confirmed for
      Ped. acidilactici UL5 using a pediocin nonproducer mutant. CONCLUSIONS: The data
      provide some evidence that these bacteria can produce bacteriocins in a complex
      medium with carbon source similar to those found in the colon. SIGNIFICANCE AND
      IMPACT OF THE STUDY: This study demonstrates the capacity of lactic acid bacteria
      to produce their bacteriocins in a medium simulating the nutrient composition of
      the large intestine.

PMID- 23167819
TI  - Cyclophilin A secreted from fibroblast-like synoviocytes is involved in the
      induction of CD147 expression in macrophages of mice with collagen-induced
      arthritis.
AB  - BACKGROUND: Cyclophilin A (CypA), a member of the immunophilin family, is a
      ubiquitously distributed intracellular protein. Recent studies have shown that
      CypA is secreted by cells in response to inflammatory stimuli. Elevated levels of
      extracellular CypA and its receptor, CD147 have been detected in the synovium of
      patients with RA. However, the precise process of interaction between CypA and
      CD147 in the development of RA remains unclear. This study aimed to investigate
      CypA secretion from fibroblast-like synoviocytes (FLS) isolated from mice with
      collagen-induced arthritis (CIA) and CypA-induced CD147 expression in mouse
      macrophages. FINDINGS: CIA was induced by immunization with type II collagen in
      mice. The expression and localization of CypA and CD147 was investigated by
      immunoblotting and immunostaining. Both CypA and CD147 were highly expressed in
      the joints of CIA mice. CD147 was expressed in the infiltrated macrophages in the
      synovium of CIA mice. In vitro, spontaneous CypA secretion from FLS was detected
      and this secretion was increased by stimulation with lipopolysaccharide. CypA
      markedly increased CD147 levels in macrophages. CONCLUSIONS: These findings
      suggest that an interaction in the synovial joints between extracellular CypA and
      CD147 expressed by macrophages may be involved in the mechanisms underlying the
      development of arthritis.

PMID- 23167820
TI  - A systematic three-dimensional echocardiographic approach to assist surgical
      planning in double outlet right ventricle.

PMID- 23167822
TI  - Echocardiographic diagnosis of Hodgkin's lymphoma in a patient with suspected
      endocarditis.

PMID- 23167823
TI  - Palladium-catalyzed Kumada coupling reaction of bromoporphyrins with silylmethyl
      Grignard reagents: preparation of silylmethyl-substituted porphyrins as a
      multipurpose synthon for fabrication of porphyrin systems.
AB  - We have developed an efficient method for preparing silylmethyl-substituted
      porphyrins via the palladium-catalyzed Kumada cross-coupling reaction of
      bromoporphyrins with silylmethyl Grignard reagents. We demonstrated the synthetic
      utility of these silylmethylporphyrins as a multipurpose synthon for fabricating
      porphyrin derivatives through a variety of transformations of the silylmethyl
      groups, including the DDQ-promoted oxidative conversion to CHO, CH(2)OH,
      CH(2)OMe, and CH(2)F functionalities and the fluoride ion-mediated desilylative
      introduction of carbon-carbon single and double bonds.

PMID- 23167824
TI  - Participatory action research: moving beyond the mental health 'service user'
      identity.
AB  - Contemporary models of involvement within statutory services pay little regard to
      the identity of individuals beyond the 'service user' label and in doing so
      unwittingly perpetuate and sustain the negative impact of mental illness. The aim
      of this paper is to discuss the process of a 3-year participatory action research
      study facilitated by a mental health nurse. It highlights the perspective of
      those involved as co-researchers, all having experience of accessing statutory
      mental health services. It identifies both the process and the impact of this
      type of involvement on them illustrating their move beyond an illness identity.
      The study involved them undertaking a series of interviews with other service
      users in relation to their life stories. They subsequently mapped and analysed
      the transcripts. In order that the people were enabled to undertake these roles
      the study included a process of interviewing and appointing service user
      researchers followed by a programme of training workshops, supervision and
      discussion group/peer support. The accounts provided reflect the six researchers'
      attempts to make sense of their experience and reveal the path of transformation
      through collaboration.

PMID- 23167821
TI  - Transient hypercapnia reveals an underlying cerebrovascular pathology in a murine
      model  for HIV-1 associated neuroinflammation: role  of NO-cGMP signaling and
      normalization by inhibition of cyclic nucleotide phosphodiesterase-5.
AB  - BACKGROUND: Cerebral blood flow (CBF) is known to be dysregulated in persons with
      human immunodeficiency virus 1 (HIV-1), for uncertain reasons. This is an
      important issue because impaired vasoreactivity has been associated with
      increased risk of ischemic stroke, elevated overall cardiovascular risk and
      cognitive impairment. METHODS: To test whether dysregulation of CBF might be due
      to virally-induced neuroinflammation, we used a well-defined animal model (GFAP
      driven, doxycycline-inducible HIV-1 Tat transgenic (Tat-tg) mice). We then
      exposed the mice to a brief hypercapnic stimulus, and assessed cerebrovascular
      reactivity by measuring 1) changes in cerebral blood flow, using laser Doppler
      flowmetry and 2) changes in vascular dilation, using in vivo two-photon imaging.
      RESULTS: Exposure to brief hypercapnia revealed an underlying cerebrovascular
      pathology in Tat-tg mice. In control animals, brief hypercapnia induced a brisk
      increase in cortical flow (20.8% above baseline) and vascular dilation, as
      measured by laser Doppler flowmetry and in vivo two-photon microscopy. These
      responses were significantly attenuated in Tat-tg mice (11.6% above baseline),
      but cortical microvascular morphology and capillary density were unaltered,
      suggesting that the functional pathology was not secondary to vascular
      remodeling. To examine the mechanistic basis for the diminished cerebrovascular
      response to brief hypercapnia, Tat-tg mice were treated with 1) gisadenafil, a
      phosphodiesterase 5 (PDE5) inhibitor and 2) tetrahydrobiopterin (BH4).
      Gisadenafil largely restored the normal increase in cortical flow following
      hypercapnia in Tat-tg mice (17.5% above baseline), whereas BH4 had little effect.
      Gisadenafil also restored the dilation of small (<25 MUm) arterioles following
      hypercapnia (19.1% versus 20.6% diameter increase in control and Tat-tg plus
      gisadenafil, respectively), although it failed to restore full dilation of larger
      (>25 MUm) vessels. CONCLUSIONS: Taken together, these data show that HIV
      associated neuroinflammation can cause cerebrovascular pathology through effects
      on cyclic guanosine monophosphate (cGMP) metabolism and possibly on PDE5
      metabolism.

PMID- 23167825
TI  - Summary of the ACS symposium on Advances in Food Allergen Detection.
AB  - A symposium titled "Advances in Food Allergen Detection" was held at the 243rd
      National Meeting of the American Chemical Society (ACS) in March 2012 in San
      Diego, CA, and was sponsored by the ACS Division of Agricultural and Food
      Chemistry. The purpose of the symposium was to convene the leaders in the food
      allergen analysis field for presentations on, and discussions of, the state of
      the art, new developments, and critical challenges in the detection and
      quantitation of allergenic proteins in foods. Twenty-five presentations were
      delivered by speakers representing academic, government, and industrial
      institutions in 10 countries. The presentations covered all aspects of food
      allergens, including a historical progress review, regulatory policies, clinical
      practices, food-processing effects, food production equipment cross-contamination
      and cleaning, and the performance of several food allergen analytical strategies
      and technologies. This paper is intended to provide a brief summary of the
      presentations as well as a record of the proceedings of the symposium, which was
      deemed a great success in advancing food allergen analysis. 

PMID- 23167826
TI  - Genotype distribution of human papillomavirus (HPV) in histological sections of
      cervical intraepithelial neoplasia and invasive cervical carcinoma in Madrid,
      Spain.
AB  - BACKGROUND: Human Papillomavirus (HPV) genotype distribution and co-infection
      occurrence was studied in cervical specimens from the city of Madrid (Spain), as
      a contribution to the knowledge of Human Papillomavirus genotype distribution and
      prevalence of carcinogenic HPV types in cervical lesions in Spain. METHODS: A
      total of 533 abnormal specimens, from the Hospital General Universitario
      "Gregorio Maranon" of Madrid, were studied. These included 19 benign lesions, 349
      cervical intraepithelial neoplasias 1 (CIN1), 158 CIN2-3 and 7 invasive cervical
      carcinomas (ICC). HPV genotyping was performed using PCR and tube array
      hybridization. RESULTS: We detected 20 different HPV types: 13 carcinogenic high
      risk HPV types (HR-HPVs), 2 probably carcinogenic high-risk HPV types (PHR-HPVs)
      and 5 carcinogenic low-risk HPV types (LR-HPVs). The most frequent HPV genotypes
      found in all specimens were HPV16 (26.0%), 31 (10.7%) and 58 (8.0%). HPV 18 was
      only detected in 5.0%. Co-infections were found in 30.7% of CIN 1 and 18.4% cases
      of CIN2-3. The highest percentage of HR HPVs was found in those specimens with a
      CIN2-3 lesion (93.7%). CONCLUSION: As our study shows the current tetravalent
      vaccine could be effective in our geographical area for preventing all the
      invasive cervical carcinomas. In addition, upon the estimates of the important
      presence of other HR-HPV types - such as 31, 58, 33 and 52 - in different
      preneoplasic lesions the effectiveness of HPV vaccination in our geographical
      area, and others with similar genotype distribution, should be limited.

PMID- 23167827
TI  - Highly transparent and conductive films of densely aligned ultrathin Au nanowire
      monolayers.
AB  - The combination of low electrical resistance and high optical transparency in a
      single material is very uncommon. Developing these systems is a scientific
      challenge and a technological need, to replace ITO in flexible electronic
      components and other highly demanding applications. Here we report a facile
      method to prepare single layers of densely aligned ultrathin Au-nanowires,
      homogeneous over cm(2) areas. The as-deposited films show an electrical/optical
      performance competitive with ITO and graphene-based electrodes. Moreover, the Au
      films show a good stability under ambient conditions, and the large aspect ratio
      of the ultrathin nanowires makes them perfect for deposition in flexible
      substrates.

PMID- 23167828
TI  - Cause-specific mortality among patients with epilepsy: results from a 30-year
      cohort study.
AB  - PURPOSE: Death rates of patients with epilepsy are two to three times higher than
      expected. The aim of our study was to further delineate the causes and the
      patterns of premature death in patients with epilepsy. METHODS: We included all
      patients who were prospectively enrolled between 1970 and 1999 in our epilepsy
      outpatient clinical database. Patients were followed until death or December 31,
      2003. Standardized mortality ratios (SMRs) were calculated using reference rates
      from the same region. KEY FINDINGS: After 48,595 person years of follow-up, 648
      of 3,334 patients had died, resulting in an overall SMR of 2.2 (95% confidence
      interval [CI] 2.0-2.4). The highest SMRs were for patients aged 26-45 years (6.8,
      95% CI 3.8-11.2) and with symptomatic epilepsies (3.1, 95% CI 2.3-4.9); those for
      cryptogenic causes (2.2, 95% CI 1.6-3.1) were also elevated, whereas those for
      idiopathic causes were not increased (2.7, 95% CI 0.7-7.0) after 2 years of
      follow-up. SMRs for patients with persistent seizures (3.3, 95% CI 2.6-4.4) were
      higher than those for seizure-free patients (1.4, 95% CI 0.8-2.3). The highest
      cause-specific SMRs were for epilepsy (91.6, 95% CI 66.3-123.4), brain tumors
      (22.7, 95% CI 15.7-31.8), and external causes (2.4, 95% CI 1.8-3.3) at end of
      study period. SIGNIFICANCE: Epilepsy patients have a higher-than-expected risk of
      death throughout life and especially during the first 2 years following
      diagnosis. Standardized mortality rates were especially high in younger patients
      and in patients with symptomatic epilepsies. Persistent seizures are strongly
      related to excess mortality.

PMID- 23167829
TI  - Inhibitor-induced conformational shifts and ligand-exchange dynamics for HIV-1
      protease measured by pulsed EPR and NMR spectroscopy.
AB  - Double electron-electron resonance (DEER) spectroscopy was utilized to
      investigate shifts in conformational sampling induced by nine FDA-approved
      protease inhibitors (PIs) and a nonhydrolyzable substrate mimic for human
      immunodeficiency virus type 1 protease (HIV-1 PR) subtype B, subtype C, and
      CRF_01 A/E. The ligand-bound subtype C protease has broader DEER distance
      profiles, but trends for inhibitor-induced conformational shifts are comparable
      to those previously reported for subtype B. Ritonavir, one of the strong-binding
      inhibitors for subtypes B and C, induces less of the closed conformation in
      CRF_01 A/E. (1)H-(15)N heteronuclear single-quantum coherence (HSQC) spectra were
      acquired for each protease construct titrated with the same set of inhibitors.
      NMR (1)H-(15)N HSQC titration data show that inhibitor residence time in the
      protein binding pocket, inferred from resonance exchange broadening, shifting or
      splitting correlates with the degree of ligand-induced flap closure measured by
      DEER spectroscopy. These parallel results show that the ligand-induced
      conformational shifts resulting from protein-ligand interactions characterized by
      DEER spectroscopy of HIV-1 PR obtained at the cryogenic temperature are
      consistent with more physiological solution protein-ligand interactions observed
      by solution NMR spectroscopy.

PMID- 23167831
TI  - Filtration effectiveness of HVAC systems at near-roadway schools.
AB  - Concern for the exposure of children attending schools located near busy roadways
      to toxic, traffic-related air pollutants has raised questions regarding the
      environmental benefits of advanced heating, ventilation, and air-conditioning
      (HVAC) filtration systems for near-road pollution. Levels of black carbon and
      gaseous pollutants were measured at three indoor classroom sites and at seven
      outdoor monitoring sites at Las Vegas schools. Initial HVAC filtration systems
      effected a 31-66% reduction in black carbon particle concentrations inside three
      schools compared with ambient air concentrations. After improved filtration
      systems were installed, black carbon particle concentrations were reduced by 74
      97% inside three classrooms relative to ambient air concentrations. Average black
      carbon particle concentrations inside the schools with improved filtration
      systems were lower than typical ambient Las Vegas concentrations by 49-96%.
      Gaseous pollutants were higher indoors than outdoors. The higher indoor
      concentrations most likely originated at least partially from indoor sources,
      which were not targeted as part of this intervention. PRACTICAL IMPLICATIONS:
      Recent literature has demonstrated adverse health effects in subjects exposed to
      ambient air near major roadways. Current smart growth planning and infill
      development often require that buildings such as schools are built near major
      roadways. Improving the filtration systems of a school's HVAC system was shown to
      decrease children's exposure to near-roadway diesel particulate matter. However,
      reducing exposure to the gas-phase air toxics, which primarily originated from
      indoor sources, may require multiple filter passes on recirculated air.

PMID- 23167830
TI  - The anti-HIV microbicide candidate RC-101 inhibits pathogenic vaginal bacteria
      without harming endogenous flora or mucosa.
AB  - PROBLEM: Vaginal microbicides represent a promising approach for preventing
      heterosexual HIV transmission. However, preclinical evaluation should be
      conducted to ensure that microbicides will be safe for human cells and healthy
      microflora of the female reproductive tract. One microbicide candidate, RC-101,
      has been effective and well tolerated in preliminary cell culture and macaque
      models. However, the effect of RC-101 on primary vaginal tissues and resident
      vaginal microflora requires further evaluation. METHOD OF STUDY: We treated
      primary vaginal tissues and vaginal bacteria, both pathogenic and commensal, with
      RC-101 to investigate effects of this microbicide. RESULTS: RC-101 was well
      tolerated by host tissues, and also by commensal vaginal bacteria.
      Simultaneously, pathogenic vaginal bacteria, which are known to increase
      susceptibility to HIV acquisition, were inhibited by RC-101. CONCLUSIONS: By
      establishing vaginal microflora, the specific antibacterial activity of RC-101
      may provide a dual mechanism of HIV protection. These findings support
      advancement of RC-101 to clinical trials.

PMID- 23167832
TI  - Benefit of multiple sessions of perilesional repetitive transcranial magnetic
      stimulation for an effective rehabilitation of visuospatial function.
AB  - Noninvasive neurostimulation techniques have been used alone or in conjunction
      with rehabilitation therapy to treat the neurological sequelae of brain damage
      with rather variable therapeutic outcomes. One potential factor limiting a
      consistent success for such techniques may be the limited number of sessions
      carried out in patients, despite reports that their accrual may play a key role
      in alleviating neurological deficits long-term. In this study, we tested the
      effects of seventy consecutive sessions of perilesional high-frequency (10 Hz)
      repetitive transcranial magnetic stimulation (rTMS) in the treatment of chronic
      neglect deficits in a well-established feline model of visuospatial neglect.
      Under identical rTMS parameters and visuospatial testing regimes, half of the
      subjects improved in visuospatial orienting performance. The other half
      experienced either none or extremely moderate ameliorations in the neglected
      hemispace and displayed transient patterns of maladaptive visuospatial behavior.
      Detailed analyses suggest that lesion location and extent did not account for the
      behavioral differences observed between these two groups of animals. We conclude
      that multi-session perilesional rTMS regimes have the potential to induce
      functional ameliorations following focal chronic brain injury, and that
      behavioral performance prior to the onset of the rTMS treatment is the factor
      that best predicts positive outcomes for noninvasive neurostimulation treatments
      in visuospatial neglect.

PMID- 23167834
TI  - Association between common CYP1A2 polymorphisms and theophylline metabolism in
      non-smoking healthy volunteers.
AB  - This study was designed to investigate the impact of cytochrome P450 (CYP) 1A2
      polymorphisms on theophylline metabolism in a non-smoking healthy male Chinese
      population. Four polymorphisms CYP1A2 1C (G-3860A), G-3113A, CYP1A2 1F (C-163A)
      and CYP1A2 1B (C-5347T) were screened in 238 unrelated male volunteers. Then, a
      single oral 200-mg dose of theophylline was administered to 37 volunteers, who
      were selected from 238 volunteers based on the CYP1A2 genotype. CYP1A2 activities
      were evaluated by plasma 1,7-dimethylxanthine/caffeine ratios (17X/137X) after
      administration of 100-mg caffeine. The plasma concentrations of theophylline, 17X
      and 137X were determined by high-performance liquid chromatography. The activity
      of CYP1A2 was lower in volunteers with the -3113 AA genotype compared with those
      with the -3113 AG genotype (0.35 +/- 0.04 versus 0.48 +/- 0.07, p = 0.016) or the
      -3113 GG genotype (0.35 +/- 0.04 versus 0.58 +/- 0.22, p = 0.037). CYP1A2 1F
      polymorphisms were associated with increased CYP1A2 activity in volunteers with 
      3860G/-3113G/5347C homozygosity (0.66 +/- 0.24 versus 0.46 +/- 0.05, p = 0.034).
      However, theophylline metabolism showed no difference among volunteers carrying
      different haplotype pairs. CYP1A2 genetic polymorphisms influenced CYP1A2 enzyme
      activity as measured by caffeine, but CYP1A2 gene polymorphisms appeared to have
      limited influence on theophylline metabolism in our study.

PMID- 23167833
TI  - Liposomal amphotericin B as a treatment for human leishmaniasis.
AB  - INTRODUCTION: Leishmaniasis is a parasitic disease transmitted by phlebotomine
      sandflies. Between 700,000 and 1.2 million cases of cutaneous leishmaniasis and
      between 200,000 and 400,000 cases of visceral leishmaniasis (VL), which is fatal
      if left untreated, occur annually worldwide. Liposomal amphotericin B (LAMB),
      alone or in combination with other drugs, has been extensively studied as VL
      treatment, but data on routine field use are limited, and several challenges to
      patients' access to this life-saving drug remain. AREAS COVERED: This article
      provides a review of clinical studies on LAMB for VL and other forms of
      leishmaniasis. The current development of generic versions of LAMB and related
      challenges are also discussed. EXPERT OPINION: LAMB proved to be highly
      efficacious and safe in over 8000 VL patients treated by MEdecins Sans Frontieres
      in South Asia, and its use was feasible even at primary healthcare level. Despite
      requiring higher doses, LAMB is the drug of choice to treat vulnerable groups
      (e.g., pregnant or HIV positive) and relapsing VL patients in East Africa. LAMB
      should be included in national VL guidelines and registered in all VL endemic
      countries. Its cost should be further reduced and regulatory pathways to prove
      bioequivalence for generic LAMB products should be implemented.

PMID- 23167835
TI  - Effect of galactooligosaccharides and Bifidobacterium animalis Bb-12 on growth of
      Lactobacillus amylovorus DSM 16698, microbial community structure, and metabolite
      production in an in vitro colonic model set up with human or pig microbiota.
AB  - A validated in vitro model of the large intestine (TIM-2), set up with human or
      pig faeces, was used to evaluate the impact of potentially probiotic
      Lactobacillus amylovorus DSM 16698, administered alone (i), in the presence of
      prebiotic galactooligosaccharides (GOS) (ii), and co-administered with probiotic
      Bifidobacterium animalis ssp. lactis Bb-12 (Bb-12) (iii) on GOS degradation,
      microbial growth (L. amylovorus, lactobacilli, bifidobacteria and total bacteria)
      and metabolite production. High performance anion exchange chromatography
      revealed that GOS degradation was more pronounced in TIM-2 inoculated with pig
      faeces than with human faeces. Denaturing gradient gel electrophoresis profiling
      of PCR-amplified 16S rRNA genes detected a more complex Lactobacillus spp.
      community in pig faecal material than in human faecal inoculum. According to 16S
      rRNA gene-targeted qPCR, GOS stimulated the growth of lactobacilli and
      bifidobacteria in faecal material from both materials. The cumulative production
      of short chain fatty acids and ammonia was higher (P < 0.05) for pig than for
      human faeces. However, lactate accumulation was higher (P < 0.05) in the human
      model and increased after co-administration with GOS and Bb-12. This study
      reinforced the notion that differences in microbiota composition between target
      host organisms need to be considered when animal data are extrapolated to human,
      as is often done with pre- and probiotic intervention studies.

PMID- 23167836
TI  - The effect of granulocyte colony-stimulating factor administration on carbon
      monoxide neurotoxicity in rats.
AB  - Granulocyte colony-stimulating factor (G-CSF) is considered to be a novel
      neuroprotective agent. Beneficial effects have been demonstrated by
      administrating G-CSF in different experimental stroke models. In this study, we
      evaluated the efficacy of G-CSF therapy on carbon monoxide (CO) neurotoxicity in
      rats exposed to acute CO poisoning. Immediately after exposure to 3,000 ppm of CO
      for 60 minutes, 50, 100, and 150 ug/kg of G-CSF or normal saline were
      administered to rats. Rats were sacrificed after 24 hours for serum marker
      analysis or 1 week for histopathological examination. Brain sections were stained
      with hematoxylin and eosin to assess leukocyte infiltration and hippocampal
      injury and with Luxol fast blue to assess demyelination. S100beta and glial
      fibrillary acidic protein (GFAP) serum levels were evaluated by commercial enzyme
      linked immunosorbent assay kits. According to histopathological findings, G-CSF
      administration significantly restricted white-matter demyelination (150 ug/kg) (P
      = 0.006). Also, serum levels of S100beta in G-CSF-treated groups (100 and 150
      ug/kg) decreased significantly (P < 0.01 and P < 0.05, respectively). In all
      does, G-CSF significantly reduced serum levels of GFAP (P < 0.01 for 50 ug/kg and
      P < 0.001 for other doses). Administration of G-CSF after CO poisoning attenuates
      brain cell damage through remyelination. G-CSF also decreases levels of related
      biomarkers, such as S100beta and GFAP.

PMID- 23167837
TI  - A pure invasive cribriform carcinoma of the breast with bone metastasis if
      untreated for thirteen years: a case report and literature review.
AB  - We report a case of pure invasive cribriform carcinoma of the breast, which had
      been untreated for thirteen years, being found with bone metastasis at initial
      presentation, because distant metastasis is rarely found in this tumor. A fifty
      nine-year-old postmenopausal woman presented with a large left breast mass.
      Although she had noticed a lump in a left breast thirteen years ago, she had not
      sought treatment. The tumor had enlarged gradually since from one year before and
      become ulcerated. The two enlarged axillary lymph nodes were also palpable. After
      two cycles of neoadjuvant chemotherapy, she underwent left radial mastectomy with
      a free skin graft. Emission computed tomography result has confirmed bone
      metastasis. The histological diagnosis of the tumor revealed the pure invasive
      cribriform carcinoma, since over than ninety percent of invasive tumor components
      showed a characteristic cribriform growth, and the remainder was tubular
      carcinoma. She has been well without evidence of tumor recurrence for seven years
      after surgery and several routine postoperative therapies. Although with
      favorable prognosis, pure invasive cribriform carcinoma is still possible to
      develop into the advanced (Stage four) breast cancer if untreated for a long
      time. However, the survival of this patient for free disease after several
      locoregional and systemic therapies maybe provide a supplement for invasive
      cribriform carcinoma's excellent prognosis.

PMID- 23167838
TI  - Rapid and label-free monitoring of exonuclease III-assisted target recycling
      amplification.
AB  - Target recycling-oriented amplification has been widely applied for sensitive
      detection of DNA, RNA, and proteins due to its successful overcoming the inherent
      limitation of target-to-signal ratio of 1:1 in the traditional hybridization
      assay. Exonuclease III (Exo III) is usually used as the cleavage enzyme in the
      target recycling-oriented amplification because of its easy availability, high
      catalytic activity, and wide applicability. Even though Exo III is assumed to be
      double-stranded DNA (dsDNA) specific exonuclease in most literature, its cleavage
      of single-strand DNA (ssDNA) does occur, resulting in the target-independent
      degradation of probes. Herein, we design an intramolecular displacement probe
      with the capability of resistance to the nonspecific digestion of Exo III and
      fast hybridization kinetics. Through the substitution of 2-aminopurine for
      adenine in the intramolecular displacement probes, we develop a rapid and label
      free approach to monitor Exo III-assisted target recycling amplification. We
      further demonstrate that this method can be used for the detection of DNA and
      proteins with excellent specificity and high sensitivity. Importantly, this
      method can be extended to rapid, label-free and multiplexed detection of various
      nucleic acids, proteins, and small molecules using different kinds of fluorescent
      nucleotide analogues and specific aptamers.

PMID- 23167839
TI  - Left main coronary in-stent intimal hyperplasia and hemodynamics as detected by
      contrast-enhanced transesophageal echocardiography.
AB  - PATIENTS AND METHODS: In-stent hemodynamics were studied by transesophageal
      echocardiography (TEE) in a group of 54 patients after left main coronary artery
      stenting, during a 6-month follow-up. TEE was performed within 24 hours after
      stenting and at 1- and 3-month follow-up. Pulsed wave and color Doppler signals
      were enhanced by IV administration of Levovist. RESULTS: Angiographic immediate
      success was obtained in all patients. No in-hospital death occurred. Ten patients
      (18.4%) complained of recurrent angina at the follow-up of 4.8 +/- 1.2 months.
      Both TEE and coronary angiography confirmed in-stent restenosis in all. Thirty
      nine patients (68.5%) remained symptoms free. Mean late loss in these patients
      was 0.69 +/- 0.20 mm. A linear significant positive relation between mean late
      loss values and diastolic coronary velocity (r: 0.89, P < 0.001) was found. After
      3- and 6-month follow-up, PDV showed a significant increase in comparison with
      basal values (0.7 +/- 0.3 and 0.6 +/- 0.26 vs. 0.32 +/- 0.2 cm/sec, P < 0.01).
      All patients with restenosis showed a significant increase of diastolic coronary
      velocity in comparison with basal values (2.89 +/- 0.25 cm/sec, P < 0.001).
      CONCLUSION: TEE can predict the development of in-stent intimal hyperplasia in
      patients with unprotected left main coronary artery stenting.

PMID- 23167840
TI  - The validity of different display monitors in the assessment of dental implant
      site dimensions in cone beam computed tomography images.
AB  - OBJECTIVE: To determine if the differing contrast resolution of various LCD
      monitors affects the reliability or accuracy of measurements of proposed implant
      sites. MATERIALS AND METHODS: Edentulous areas of human dry skulls were marked
      with radiopaque markers in order to standardize the plane of the transverse cross
      sections of the ridges and path of measurements. The skulls were imaged by a CBCT
      device and the images stored in proprietary format on the workstation. The data
      sets were then transferred, with the proprietary reformatting software, to two
      different laptops using CDs. Transverse cross-sectional images of the ridges were
      reformatted on all three computers and ridge dimensions were recorded using the
      linear measurement tool of the proprietary software. Ridge dimensions were
      recorded directly from the three different monitors by two observers and compared
      to measurements recorded directly from the bone. The measurement errors and intra
      and inter-examiner reliability were calculated for each monitor and compared
      with each other. RESULTS: Intra- and inter-examiner reliability scores for the
      measurements recorded from all three devices were very high and ranged between
      0.993-0.999. The mean of the absolute errors was 0.55 mm for the workstation,
      0.61 mm for laptop 1 and 0.68 mm for laptop 2. The absolute errors were
      statistically significant for all three monitors (p-value < 0.001), but there was
      no statistically significant difference between the absolute errors obtained from
      the three monitors. CONCLUSIONS: No differences in the reliability or accuracy of
      measurements of implant site dimensions were obtained using color LCD monitors
      with different contrast resolution capabilities.

PMID- 23167841
TI  - Improved electronic properties from third-order SCC-DFTB with cost efficient post
      SCF extensions.
AB  - The present work outlines the implementation and performance of two cost
      efficient post-SCF extensions into the third-order SCC-DFTB code. The first one,
      the charge model 3 (CM3), corrects for errors in bond dipoles for an improved
      description of molecular charge distribution as compared to the standard Mulliken
      partitioning scheme. The second one focuses on the response of the charge
      density, that is, the electronic molecular polarizability, described inaccurately
      from SCC-DFTB due to the usage of a minimal atomic orbital basis. Here, a
      variational approach, based on scaled dipole integrals, was implemented, which
      clearly outperforms standard finite electric field approaches for polarizability
      calculations by approximately 1 order of magnitude. Both extensions in the
      present work rely on a set of empirical parameters, which were fitted against 112
      organic molecules to match a reference data set from full density functional
      calculations with a large basis. As an achievement, notably improved electronic
      properties, that is, molecular dipole moments and polarizabilities, result from
      SCC-DFTB calculations at negligible additional computational cost. Furthermore,
      the accuracy of infrared and Raman intensities was tested as first-order
      derivatives of the new dipoles and polarizabilities as a function of normal mode
      vibrations. As a result, the current implementations cannot contribute to an
      improved prediction of relative intensity pattern from SCC-DFTB as compared to ab
      initio reference data.

PMID- 23167842
TI  - Regulation of genes involved in cell wall synthesis and structure during Ustilago
      maydis dimorphism.
AB  - The cell wall is the structure that provides the shape to fungal cells and
      protects them from the difference in osmotic pressure existing between the
      cytosol and the external medium. Accordingly, changes in structure and
      composition of the fungal wall must occur during cell differentiation, including
      the dimorphic transition of fungi. We analyzed, by use of microarrays, the
      transcriptional regulation of the 639 genes identified to be involved in cell
      wall synthesis and structure plus the secretome of the Basidiomycota species
      Ustilago maydis during its dimorphic transition induced by a change in pH. Of
      these, 189 were differentially expressed during the process, and using as control
      two monomorphic mutants, one yeast like and the other mycelium constitutive, 66
      genes specific of dimorphism were identified. Most of these genes were up
      regulated in the mycelial phase. These included CHS genes, genes involved in beta
      1,6-glucan synthesis, N-glycosylation, and proteins containing a residue of
      glycosylphosphatidylinositol, and a number of genes from the secretome. The
      possible significance of these data on cell wall plasticity is discussed.

PMID- 23167844
TI  - Efficacy of various "classic" echocardiographic and laboratory indices in
      distinguishing the "gray zone" between athlete's heart and hypertrophic
      cardiomyopathy: a pilot study.
AB  - Left ventricular hypertrophy (LVH) with intraventricular septum thickness (IVST)
      between 1.2 and 1.5 cm in athletes represents a "gray zone" between physiologic
      adaptation and mild hypertrophic cardiomyopathy (HCM). Various echo and
      laboratory parameters have been reported till now in the literature to
      discriminate the "gray zone" entities. Aim of this study was to assess the
      efficacy of these "classic" parameters in differentiating physiologic LVH in
      athletes from mild HCM in a highly selected population. Nine highly trained
      athletes with IVST (1.28 +/- 0.07 cm), 9 patients with mild HCM (1.38 +/- 0.11
      cm), and 26 athletes without LVH (1.06 +/- 0.09 cm; P < 0.0005) underwent
      echocardiographic study, cardiopulmonary treadmill exercise stress test, and
      brain natriuretic peptide (BNP) measurement before and after exercise. Among all
      parameters tested, 7 were found to significantly differ between "gray zone"
      groups. After bootstrapping analysis, it was found that athletes with left
      ventricular end-diastolic diameter <4.74 cm, mitral deceleration time >200 ms,
      isovolumic relaxation time >94 ms, tricuspid E/A < 1.63, septum Em < 9.5 cm/sec,
      relative wall thickness >0.445, and a BNP value at rest >9.84 pg/mL had a greater
      possibility for having underlying cardiomyopathy. A 10-point score based on these
      parameters showed accuracy (area under the curve = 0.958 [95%CI: 0.738-1.0; P =
      0.00005, standard error = 0.0342]) for revealing HCM in a gray zone athletic
      population. Differentiation of adaptive LVH versus HCM in a gray zone population
      could be facilitated by recognition of certain features referring to LV
      dimensions, diastolic function, and BNP.

PMID- 23167843
TI  - Let-7 miRNA-binding site polymorphism in the KRAS 3'UTR; colorectal cancer
      screening population prevalence and influence on clinical outcome in patients
      with metastatic colorectal cancer treated with 5-fluorouracil and oxaliplatin +/-
      cetuximab.
AB  - BACKGROUND: Recent studies have reported associations between a variant allele in
      a let-7 microRNA complementary site (LCS6) within the 3'untranslated region
      (3'UTR) of KRAS (rs61764370) and clinical outcome in metastatic colorectal cancer
      (mCRC) patients receiving cetuximab. The variant allele has also been associated
      with increased cancer risk. We aimed to reveal the incidence of the variant
      allele in a colorectal cancer screening population and to investigate the
      clinical relevance of the variant allele in mCRC patients treated with 1st line
      Nordic FLOX (bolus 5-fluorouracil/folinic acid and oxaliplatin) +/- cetuximab.
      METHODS: The feasibility of the variant allele as a risk factor for CRC was
      investigated by comparing the LCS6 gene frequencies in 197 CRC patients, 1060
      individuals with colorectal polyps, and 358 healthy controls. The relationship
      between clinical outcome and LCS6 genotype was analyzed in 180 mCRC patients
      receiving Nordic FLOX and 355 patients receiving Nordic FLOX + cetuximab in the
      NORDIC-VII trial (NCT00145314). RESULTS: LCS6 frequencies did not vary between
      CRC patients (23%), individuals with polyps (20%), and healthy controls (20%) (P
      = 0.50). No statistically significant differences were demonstrated in the NORDIC
      VII cohort even if numerically increased progression-free survival (PFS) and
      overall survival (OS) were found in patients with the LCS6 variant allele (8.5
      (95% CI: 7.3-9.7 months) versus 7.8 months (95% CI: 7.4-8.3 months), P = 0.16 and
      23.5 (95% CI: 21.6-25.4 months) versus 19.5 months (95% CI: 17.8-21.2 months), P
      = 0.31, respectively). Addition of cetuximab seemed to improve response rate more
      in variant carriers than in wild-type carriers (from 35% to 57% versus 44% to
      47%), however the difference was not statistically significant (interaction P =
      0.16). CONCLUSIONS: The LCS6 variant allele does not seem to be a risk factor for
      development of colorectal polyps or CRC. No statistically significant effect of
      the LCS6 variant allele on response rate, PFS or OS was found in mCRC patients
      treated with 1st line Nordic FLOX +/- cetuximab.

PMID- 23167845
TI  - A single residue change leads to a hydroxylated product from the class II
      diterpene cyclization catalyzed by abietadiene synthase.
AB  - Class II diterpene cyclases catalyze bicyclization of geranylgeranyl diphosphate.
      While this reaction typically is terminated via methyl deprotonation to yield
      copalyl diphosphate, in rare cases hydroxylated bicycles are produced instead.
      Abietadiene synthase is a bifunctional diterpene cyclase that usually produces a
      copalyl diphosphate intermediate. Here it is shown that substitution of aspartate
      for a conserved histidine in the class II active site of abietadiene synthase
      leads to selective production of 8alpha-hydroxy-CPP instead, demonstrating
      striking plasticity.

PMID- 23167846
TI  - Psychometric assessment of the Chinese version of the decisional conflict scale
      in Chinese women making decision for breast cancer surgery.
AB  - OBJECTIVE: The decisional conflict scale (DCS) measures the perception of
      uncertainty in choosing options, factors contributing to decision conflict and
      effective decision making. This study examined the validity and reliability of
      the Chinese version of the DCS in Hong Kong Chinese women deciding breast cancer
      (BC) surgery. METHOD: A Chinese version of the 16-item DCS was administered to
      471 women awaiting initial consultation for BC diagnosis. Confirmatory factor
      analysis (CFA) assessed the factor structure. Internal consistency, and
      convergent and discriminant validities of the factor structure were assessed.
      RESULTS: CFA revealed the original factor structure of the DCS showed poor fit to
      this sample. Exploratory factor analysis revealed an alternative three-factor
      structure, Informed and Values Clarity, Uncertainty and Effective Decision and
      Support, was optimal. Cronbach's alpha ranged from 0.51 to 0.87. Correlations
      between decision-making difficulties and satisfaction with medical consultation
      demonstrated acceptable convergent validity. Construct validity was supported by
      correlations between decision regret and psychological distress. Discriminant
      validity was supported by differentiation between delaying and non-delaying
      decision-makers. CONCLUSIONS: The three-factor DCS-14 is a valid and practical
      measure for assessing decisional conflict in deciding BC surgery. It shows good
      potential for use in assessing decision satisfaction for women diagnosed with BC.

PMID- 23167848
TI  - Thermal stability, complexing behavior, and ionic transport of polymeric gel
      membranes based on polymer PVdF-HFP and ionic liquid, [BMIM][BF4].
AB  - PVdF-HFP + IL(1-butyl-3-methylimidazolium tetrafluoroborate; [BMIM][BF(4)])
      polymeric gel membranes containing different amounts of ionic liquid have been
      synthesized and characterized by X-ray diffraction, scanning electron microscopy,
      Fourier transform infrared (FTIR), differential scanning calorimetry,
      thermogravimetric analysis (TGA), and complex impedance spectroscopic techniques.
      Incorporation of IL in PVdF-HFP polymer changes different physicochemical
      properties such as melting temperature (T(m)), thermal stability, structural
      morphology, amorphicity, and ionic transport. It is shown by FTIR, TGA (also
      first derivative of TGA, "DTGA") that IL partly complexes with the polymer PVdF
      HFP and partly remains dispersed in the matrix. The ionic conductivity of
      polymeric gel membranes has been found to increase with increasing concentration
      of IL and attains a maximum value of 1.6 * 10(-2) S.cm(-1) for polymer gel
      membrane containing 90 wt % IL at room temperature. Interestingly, the values of
      conductivity of membranes with 80 and 90 wt % of IL were higher than that of pure
      IL (100 wt %). The polymer chain breathing model has been suggested to explain
      it. The variation of ionic conductivity with temperature of these gel polymeric
      membranes follows Arrhenius type thermally activated behavior.

PMID- 23167847
TI  - mRNA blood expression patterns in new-onset idiopathic pediatric epilepsy.
AB  - PURPOSE: Determine if blood messenger RNA (mRNA) expression patterns in children
      with newly diagnosed untreated idiopathic epilepsy are different from those in
      healthy controls. Determine the differential expression patterns between epilepsy
      patients with generalized onset or partial onset seizures compared to healthy
      controls. METHODS: Whole blood was obtained from otherwise healthy pediatric
      patients with newly diagnosed untreated idiopathic epilepsy along with healthy
      pediatric controls. mRNA was isolated and hybridized to Affymetrix HGU 133 2.0+
      microarrays. Analysis was performed using Genespring. Differentially expressed
      gene lists resulted from comparison of (1) epilepsy and control groups and (2)
      seizure type subgroups with controls. Tissue expression and gene ontology
      analysis was performed using DAVID. KEY FINDINGS: Thirty-seven epilepsy patients
      and 28 controls were included. Overall, 575 genes were differentially expressed
      in subjects with epilepsy compared to controls. The generalized seizure subgroup
      versus control (GvC) gene list and the partial seizure subgroup versus control
      (PvC) gene list were different (p < 0.05). Tissue expression analysis identified
      almost half of the genes in GvC and PvC as brain based. Functional group analysis
      identified several biologically relevant pathways. In GvC, these included
      mitochondria and lymphocyte activation. In PvC, we identified apoptosis,
      inflammatory defense, and cell motion pathways. SIGNIFICANCE: A unique,
      biologically meaningful mRNA expression pattern is detectable in whole blood of
      pediatric subjects with new-onset and untreated epilepsy. This analysis finds
      many similar pathways to those identified in brain studies examining lesional
      intractable epilepsy. Blood mRNA expression patterns show promise as a target for
      biomarker development in pediatric epilepsy.

PMID- 23167849
TI  - Lipopolysaccharide induces a stromal-epithelial signalling axis in a rat model of
      chronic periodontitis.
AB  - AIM: Lipopolysaccharide is a bacterial virulence factor implicated in chronic
      periodontitis, which may penetrate the junctional epithelial barrier and basement
      membrane to insult underlying stroma. We sought to identify lipopolysaccharide
      induced global gene expression changes responsible for signalling between stroma
      and epithelium during disease onset. MATERIALS AND METHODS: Using a rat
      lipopolysaccharide periodontitis model, junctional epithelium and underlying
      stromal tissue were separately collected from healthy and diseased animals by
      laser-capture microdissection and subject to gene expression microarray analysis.
      Key gene products identified were validated in gingival epithelial and fibroblast
      cell cultures. RESULTS: Global gene expression patterns distinguishing health
      versus disease were found in and between both tissue types. In stroma, the most
      significantly altered gene ontology function group (Z >= 4.00) was cytokines,
      containing most significantly (+/-2-fold; p < 0.05) upregulated genes
      amphiregulin, IL1-beta and Fas ligand, all positive, diffusible modulators of the
      epithelial growth factor receptor pathway. In epithelium, the most significant
      changes were in downregulated FOS-related antigen-1 gene, somatostatin receptor-2
      gene and mucin-4 gene, all negative modulators of the epithelial growth factor
      receptor pathway. CONCLUSION: These results establish a periodontitis model for
      studying gene product interactions and suggests that the onset of junctional
      epithelial disease hyperproliferation involves a concerted stromal-epithelial
      signalling axis.

PMID- 23167850
TI  - Characterization of ellagitannins, gallotannins, and bound proanthocyanidins from
      California almond (Prunus dulcis) varieties.
AB  - Extractable and bound proanthocyanidins and hydrolyzable tannins were
      characterized in Nonpareil, Carmel, and Butte almond varieties from California,
      with n = 3 samples/variety. Bound proanthocyanidins were recovered from extracted
      defatted almond residue by hydrolysis with 4 N sodium hydroxide and represented 3
      21% of the total proanthocyanidin content among varieties. The bound
      proanthocyanidins were recovered primarily as monomers and dimers. In contrast,
      acid hydrolysis of extracted almond residue did not yield bound
      proanthocyanidins. Hydrolyzable tannins were characterized in aqueous acetone
      extracts of defatted almond using two-dimensional TLC and further quantitated by
      HPLC following acid hydrolysis. Almond hydrolyzable tannin content was 54.7 +/-
      2.3 mg ellagic acid and 27.4 +/- 7.3 mg gallic acid per 100 g almond among
      varieties. The tannin contents of Nonpareil, Carmel, and Butte almond varieties
      were not significantly different. Thus, bound proanthocyanidins and hydrolyzable
      tannins significantly contribute to almond polyphenol content.

PMID- 23167851
TI  - Overuse of computed tomography pulmonary angiography in the evaluation of
      patients with suspected pulmonary embolism in the emergency department.
AB  - BACKGROUND: Clinical decision rules have been developed and validated for the
      evaluation of patients presenting with suspected pulmonary embolism (PE) to the
      emergency department (ED). OBJECTIVES: The objective was to assess the percentage
      of computed tomographic pulmonary angiography (CT-PA) procedures that could have
      been avoided by use of the Wells score coupled with D-dimer testing (Wells/D
      dimer) or pulmonary embolism rule-out criteria (PERC) in ED patients with
      suspected PE. METHODS: The authors conducted a prospective cohort study of adult
      ED patients undergoing CT-PA for suspected PE. Wells score and PERC were
      calculated. A research blood sample was obtained for D-dimer testing for subjects
      who did not undergo testing as part of their ED evaluation. The primary outcome
      was PE by CT-PA or 90-day follow-up. Secondary outcomes were ED length of stay
      (LOS) and CT-PA time as defined by time from order to initial radiologist
      interpretation. RESULTS: Of 152 suspected PE subjects available for analysis
      (mean +/- SD age = 46.3 +/- 15.6 years, 74% female, 59% black or African
      American, 11.8% diagnosed with PE), 14 (9.2%) met PERC, none of whom were
      diagnosed with PE. A low-risk Wells score (<=4) was assigned to 110 (72%)
      subjects, of whom only 38 (35%) underwent clinical D-dimer testing (elevated in
      33/38). Of the 72 subjects with low-risk Wells scores who did not have D-dimers
      performed in the ED, archived research samples were negative in 16 (22%). All 21
      subjects with low-risk Wells scores and negative D-dimers were PE-negative. CT-PA
      time (median = 160 minutes) accounted for more than half of total ED LOS (median
      = 295 minutes). CONCLUSIONS: In total, 9.2 and 13.8% of CT-PA procedures could
      have been avoided by use of PERC and Wells/D-dimer, respectively.

PMID- 23167852
TI  - A novel image-based tool to reunite children with their families after disasters.
AB  - OBJECTIVES: Reuniting children with their families after a disaster poses unique
      challenges. The objective was to pilot test the ability of a novel image-based
      tool to assist a parent in identifying a picture of his or her children. METHODS:
      A previously developed image-based indexing and retrieval tool that employs two
      advanced vision search algorithms was used. One algorithm, Feature-Attribute
      Matching, extracts facial features (skin color, eye color, and age) of a
      photograph and then matches according to parental input. The other algorithm,
      User-Feedback, allows parents to choose children on the screen that appear
      similar to theirs and then reprioritizes the images in the database. This was
      piloted in a convenience sample of parent-child pairs in a pediatric tertiary
      care hospital. A photograph of each participating child was added to a
      preexisting image database. A double-blind randomized crossover trial was
      performed to measure the percentage of database reviewed and time using the
      Feature-Attribute-Matching-plus-User-Feedback strategy or User-Feedback strategy
      only. Search results were compared to a theoretical random search. Afterward,
      parents completed a survey evaluating satisfaction. RESULTS: Fifty-one parent
      child pairs completed the study. The Feature-Attribute-Matching-plus-User
      Feedback strategy was superior to the User-Feedback strategy in decreasing the
      percentage of database reviewed (mean +/- SD = 24.1 +/- 20.1% vs. 35.6 +/- 27.2%;
      mean difference = -11.5%; 95% confidence interval [CI] = -21.5% to -1.4%; p =
      0.03). Both were superior to the random search (p < 0.001). Time for both
      searches was similar despite fewer images reviewed in the Feature-Attribute
      Matching-plus-User-Feedback strategy. Sixty-eight percent of parents were
      satisfied with the search and 87% felt that this tool would be very or extremely
      helpful in a disaster. CONCLUSIONS: This novel image-based reunification system
      reduced the number of images reviewed before parents identified their children.
      This technology could be further developed to assist future family reunifications
      in a disaster.

PMID- 23167853
TI  - Effect of a physician assistant as triage liaison provider on patient throughput
      in an academic emergency department.
AB  - OBJECTIVES: Overcapacity issues plague emergency departments (EDs). Studies
      suggest that triage liaison providers (TLPs) may shorten patient length of stay
      (LOS) and reduce the proportion of patients who leave without being seen (LWBS),
      but these results are not universal. Previous studies used physicians as TLPs. We
      evaluated whether a physician assistant (PA), acting as a TLP, would shorten LOS
      and decrease LWBS rates. METHODS: The authors used an observational cohort
      controlled before-and-after study design with predefined outcome measures,
      comparing 8 pilot days to 8 control days. The TLP evaluated all Emergency
      Severity Index (ESI) level 3, 4, and 5 patients, excluding pediatric and
      behavioral health patients. RESULTS: A total of 353 patients were included on
      pilot days and 371 on control days. LOS was shorter on pilot days than control
      days (median [interquartile range {IQR}] = 229 [168 to 303] minutes vs. 270 [187
      to 372] minutes, p < 0.001). Waiting room times were similar between pilot and
      control days (median [IQR] = 69 [20 to 119] minutes vs. 70 [19 to 137] minutes, p
      = 0.408), but treatment room times were shorter (median [IQR] = 151 [92 to 223]
      minutes vs. 187 [110 to 254] minutes, p < 0.001). Finally, a lower proportion of
      patients LWBS on pilot days (1.4% vs. 9.7%, p < 0.001). CONCLUSIONS: The addition
      of a PA as a TLP was associated with a 41-minute decrease in median total LOS and
      a lower proportion of patients who LWBS. The decrease in total LOS is likely
      attributable to the addition of the TLP, with patients having shorter duration in
      treatment rooms on pilot days compared to control days.

PMID- 23167854
TI  - Single rescuer exertion using a mechanical resuscitation device: a randomized
      controlled simulation study.
AB  - OBJECTIVES: The goal of this experimental study was to investigate rescuer
      exertion when using "Animax," a manually operated hand-powered mechanical
      resuscitation device (MRD) for cardiopulmonary resuscitation (CPR), compared to
      standard basic life support (BLS). METHODS: This was a prospective, open,
      randomized, crossover simulation study. After being trained, 80 medical students
      with substantial knowledge in BLS performed one-rescuer CPR using either the MRD
      or the standard BLS for 12-minute intervals in random order. The main outcome
      parameter was the heart rate pressure product (RPP) as an index of cardiac work.
      Secondary outcome parameters were physical exhaustion quantified by the Borg
      scale (measurement of perceived exertion), Nine Hole Peg Test (NHPT; measurement
      of fine motor skills), and capillary lactate concentration during testing.
      RESULTS: While no significant difference could be found for the RPP, a
      significantly increased mean heart rate during the final minute of standard BLS
      compared to the MRD was found (139 +/- 22 beats/min vs. 135 +/- 26 beats/min, p =
      0.027). By contrast, subjective exertion using the MRD was rated significantly
      higher on the Borg scale (15.1 +/- 2.4 vs. 14.6 +/- 2.6, p = 0.027). Mean serum
      lactate concentration was significantly higher when the MRD was used compared to
      standard BLS (3.4 +/- 1.5 mmol/L vs. 2.1 +/- 1.3 mmol/L, p <= 0.001).
      CONCLUSIONS: Use of the MRD leads to a RPP of the rescuers comparable to standard
      BLS. These findings suggest that there is no clinically relevant reduction of
      exertion if this MRD is used by a single rescuer. If this kind of MRD is used for
      CPR, frequent changeovers with a second rescuer should be considered as the
      guidelines suggest for standard CPR.

PMID- 23167855
TI  - Emergency medicine journal impact factor and change compared to other medical and
      surgical specialties.
AB  - OBJECTIVES: A journal impact factor represents the mean number of citations per
      article published. Designed as one tool to measure the relative importance of a
      journal, impact factors are often incorporated into academic evaluation of
      investigators. The authors sought to determine how impact factors of emergency
      medicine (EM) journals compare to journals from other medical and surgical
      specialties and if any change has taken place over time. METHODS: The 2010 impact
      factors and 5-year impact factors for each journal indexed by the Thomson Reuters
      ISI Web of Knowledge Journal Citation Reports (JCR) were collected, and EM,
      medical, and surgical specialties were evaluated. The maximum, median, and
      interquartile range (IQR) of the current impact factor and 5-year impact factor
      in each journal category were determined, and specialties were ranked according
      to the summary statistics. The "top three" impact factor journals for each
      specialty were analyzed, and growth trends from 2001 through 2010 were examined
      with random effects linear regression. RESULTS: Data from 2,287 journals in 31
      specialties were examined. There were 23 EM journals with a current maximum
      impact factor of 4.177, median of 1.269, and IQR of 0.400 to 2.176. Of 23 EM
      journals, 57% had a 5-year impact factor available, with a maximum of 4.531,
      median of 1.325, and IQR of 0.741 to 2.435. The top three EM journals had a mean
      standard deviation (+/-SD) impact factor of 3.801 (+/-0.621) and median of 4.142
      and a mean (+/-SD) 5-year impact factor of 3.788 (+/-1.091) and median of 4.297,
      with a growth trend of 0.211 (95% confidence interval [CI] = 0.177 to 0.245; p <
      0.001). By any criterion analyzed, EM journals ranked no higher than 24th among
      31 specialties. CONCLUSIONS: Emergency medicine journals rank low in impact
      factor summary statistics and growth trends among 31 medical and surgical
      specialties.

PMID- 23167856
TI  - An international view of how recent-onset atrial fibrillation is treated in the
      emergency department.
AB  - OBJECTIVES: This study was conducted to determine if there is practice variation
      for emergency physicians' (EPs) management of recent-onset atrial fibrillation
      (RAF) in various world regions (Canada, United States, United Kingdom, and
      Australasia). METHODS: The authors completed a mail and e-mail survey of members
      from four national emergency medicine (EM) associations. One prenotification
      letter and three survey letters were sent to members of the Canadian Association
      of Emergency Physicians (CAEP; Canada-1,177 members surveyed), American College
      of Emergency Physicians (ACEP; United States-500), College of Emergency Medicine
      UK (CEM; United Kingdom-1,864), and Australasian College for Emergency Medicine
      (ACEM; Australasia-1,188) as per the modified Dillman technique. The survey
      contained 23 questions related to the management of adult patients with
      symptomatic RAF (either a first episode or paroxysmal-recurrent) where onset is
      less than 48 hours and cardioversion is considered a treatment option. Data were
      analyzed using descriptive and chi-square statistics. RESULTS: Response rates
      were as follows: overall, 40.5%; Canada, 43.0%; United States, 50.1%; United
      Kingdom, 38.1%; and Australasia, 38.0%. Physician demographics were as follows:
      72% male and mean (+/-SD) age 41.7 (+/-8.39) years. The proportions of physicians
      attempting rate control as their initial strategy are United States, 94.0%;
      Canada, 70.7%; Australasia, 61.1%; and United Kingdom, 43.1% (p < 0.0001).
      Diltiazem is the predominant agent for rate control in Canada (65.36%) and the
      United States (95.22%), while metoprolol is used in Australasia (65.94%) and the
      United Kingdom (67.64%). Cardioversion is attempted at varying rates in Canada
      (65.9%), Australasia (49.9%), United Kingdom (49.5%), and the United States
      (25.9%) (p < 0.0001). Pharmacologic cardioversion is attempted first in all
      regions, with the preferred drug being procainamide in Canada (61.93%) and
      amiodarone in Australasia (63.39%), the United Kingdom (47.97%), and the United
      States (22.41%; p < 0.0001). If drugs fail, electrical cardioversion is then
      attempted in Canada (70.64%), Australasia (46.19%), the United States (29.69%),
      and the United Kingdom (27.78%; p < 0.0001). CONCLUSIONS: There is much variation
      in emergency department (ED) management of RAF among world regions, most markedly
      for use of rate versus rhythm control, choice of drugs, and use of electrical
      cardioversion. Canadians are more likely to use an aggressive approach for
      management of RAF, whereas Americans are more likely to employ conservative
      management. U.K. and Australasian EPs fall somewhere in the middle. These
      differences demonstrate the need for better evidence, or better synthesis of
      existing knowledge, to create guidelines to guide ED management of this common
      dysrhythmia.

PMID- 23167857
TI  - Does the current definition of contrast-induced acute kidney injury reflect a
      true clinical entity?
AB  - OBJECTIVES: Contrast-induced acute kidney injury (CI-AKI) is defined as either a
      25% increase in or an absolute elevation in serum creatinine (SCr) of 0.5 mg/dL,
      48 to 72 hours after parenteral contrast exposure. The objective of this study
      was to compare the incidence and complications of AKI between patients exposed
      and those unexposed to intravenous (IV) contrast. METHODS: This was a
      retrospective cohort study using the electronic medical record of adult patients
      (>18 years) with and without contrast-enhanced abdominal or chest computed
      tomography (CT) between May 2008 and April 2009. Inclusion criteria were
      emergency department (ED) patients with normal renal function who received either
      a contrast-enhanced abdominal or a contrast-enhanced chest CT, compared to those
      unexposed to IV contrast, with a repeat SCr within 48 to 72 hours. Exclusion
      criteria were contrast exposure within 7 days before the index visit. CI-AKI in
      the contrast-exposed group and AKI in the contrast-unexposed group were defined
      by the same changes in SCr 48 to 72 hours after contrast or ED admission. Data
      were described by proportions or medians with 95% confidence intervals (CIs) or
      interquartile ranges (IQR; 25% to 75%). Group comparisons were by Mann-Whitney U
      or Fisher's exact test (alpha = 0.05, two tails). RESULTS: The contrast-exposed
      (n = 773) and contrast-unexposed (n = 2,956) patients were evenly matched for
      initial demographic, renal, and metabolic parameters. The incidence of CI-AKI/AKI
      was significantly higher for the patients unexposed versus exposed to contrast
      (8.96% vs. 5.69%, p = 0.003). There was no significant difference in mortality
      rates between contrast-exposed and unexposed patients (9.09% vs. 6.79%, p =
      0.533). CONCLUSIONS: The definition of CI-AKI for ED patients with normal renal
      function may not represent a true clinical entity and the definition warrants
      revision.

PMID- 23167858
TI  - Hyperlactatemia affects the association of hyperglycemia with mortality in
      nondiabetic adults with sepsis.
AB  - BACKGROUND: Admission hyperglycemia has been reported as a mortality risk factor
      for septic nondiabetic patients; however, hyperglycemia's known association with
      hyperlactatemia was not addressed in these analyses. OBJECTIVES: The objective
      was to determine whether the association of hyperglycemia with mortality remains
      significant when adjusted for concurrent hyperlactatemia. METHODS: This was a
      post hoc, nested analysis of a retrospective cohort study performed at a single
      center. Providers had identified study subjects during their emergency department
      (ED) encounters; all data were collected from the electronic medical record
      (EMR). Nondiabetic adult ED patients hospitalized for suspected infection, two or
      more systemic inflammatory response syndrome (SIRS) criteria, and simultaneous
      lactate and glucose testing in the ED were enrolled. The setting was the ED of an
      urban teaching hospital from 2007 to 2009. To evaluate the association of
      hyperglycemia (glucose > 200 mg/dL) with hyperlactatemia (lactate >= 4.0 mmol/L),
      a logistic regression model was created. The outcome was a diagnosis of
      hyperlactatemia, and the primary variable of interest was hyperglycemia. A second
      model was created to determine if coexisting hyperlactatemia affects
      hyperglycemia's association with mortality; the main outcome was 28-day
      mortality, and the primary risk variable was hyperglycemia with an interaction
      term for simultaneous hyperlactatemia. Both models were adjusted for
      demographics; comorbidities; presenting infectious source; and objective evidence
      of renal, respiratory, hematologic, or cardiovascular dysfunction. RESULTS: A
      total of 1,236 ED patients were included, and the median age was 77 years
      (interquartile range [IQR] = 60 to 87 years). A total of 115 (9.3%) subjects were
      hyperglycemic, 162 (13%) were hyperlactatemic, and 214 (17%) died within 28 days
      of their initial ED visits. After adjustment, hyperglycemia was significantly
      associated with simultaneous hyperlactatemia (odds ratio [OR] = 4.14, 95%
      confidence interval [CI] = 2.65 to 6.45). Hyperglycemia and concurrent
      hyperlactatemia were associated with increased mortality risk (OR = 3.96, 95% CI
      = 2.01 to 7.79), but hyperglycemia in the absence of simultaneous hyperlactatemia
      was not (OR = 0.78, 95% CI = 0.39 to 1.57). CONCLUSIONS: In this cohort of septic
      adult nondiabetic patients, mortality risk did not increase with hyperglycemia
      unless associated with simultaneous hyperlactatemia. The previously reported
      association of hyperglycemia with mortality in nondiabetic sepsis may be due to
      the association of hyperglycemia with hyperlactatemia.

PMID- 23167859
TI  - The utility of early lactate testing in undifferentiated pediatric systemic
      inflammatory response syndrome.
AB  - OBJECTIVES: Failure to recognize shock contributes to inadequate early
      resuscitation in many children with sepsis. Serum lactate levels are used to
      identify adult patients with septic shock, but physical examination diagnosis
      alone is recommended in pediatric sepsis. The authors sought to test the utility
      of lactate testing in pediatric emergency department (ED) patients with systemic
      inflammatory response syndrome (SIRS). The hypothesis was that early
      hyperlactatemia (serum lactate >= 4.0 mmol/L) would be associated with increased
      risk of organ dysfunction. METHODS: This was a prospective cohort study of
      children younger than 19 years with SIRS presenting to a pediatric ED. The
      primary outcome was organ dysfunction within 24 hours of triage; secondary
      outcomes included disposition, serious bacterial infection (SBI), treatments, and
      mortality. Study personnel measured venous lactate level on a point-of-care
      meter, with clinicians blinded to results, and patients received usual care.
      RESULTS: A total of 239 subjects were enrolled; 18 had hyperlactatemia. The
      hyperlactatemia group had a relative risk of 5.5 (95% confidence interval [CI] =
      1.9 to 16.0) of developing 24-hour organ dysfunction. As a test for organ
      dysfunction, hyperlactatemia had a positive likelihood ratio of 5.0, a
      sensitivity of 31% (95% CI = 13% to 58%), and specificity of 94% (95% CI = 90% to
      96%). Subjects with hyperlactatemia were significantly more likely to receive
      intravenous (IV) antibiotics and fluid boluses; despite increased therapy, they
      were at significantly increased risk for intensive care unit (ICU) admission and
      bacterial infection. CONCLUSIONS: Among undifferentiated children with SIRS,
      early hyperlactatemia is significantly associated with increased risk of organ
      dysfunction, resuscitative therapies, and critical illness. The addition of serum
      lactate testing to the currently recommended clinical assessment may improve
      early identification of pediatric sepsis requiring resuscitation.

PMID- 23167860
TI  - A comparative study of the surgically relevant mechanical characteristics of the
      topical skin adhesives.
AB  - OBJECTIVES: Topical skin adhesives (TSAs) offer a noninvasive alternative to
      sutures. The growing trend is to use them in addition to sutures and staples to
      add strength and provide a microbial barrier. The authors compared the mechanical
      characteristics of recently approved TSAs that are most likely to be of surgical
      relevance in the emergency department. METHODS: Linear incisions were made on
      anesthetized swine and the wounds were approximated with one of six commercially
      available TSAs. Three-dimensional bursting strength was measured with a BTC
      2000TM device. Tensile failure force was measured ex vivo using TSA-approximated
      porcine skin strips with a tensionometer. Resistance to cyclic loading was
      measured by subjecting approximated skin strips to repetitive cycles of
      rotational torque and linear tension. Viscosity was measured with a viscometer
      and setting times were measured by periodically dabbing the adhesive applied to
      skin strips with a cotton swab to determine whether it was dry. RESULTS:
      Dermabond Advanced TSA provided significantly (p < 0.00001) greater acute in vivo
      wound bursting strength and ex vivo tensile force, greater mean number of normal
      tensile loading cycles to failure (while under continuous torsional cycling), and
      longest time to failure, and the mean setting time was the shortest. CONCLUSIONS:
      Of all the TSAs tested in this study, Dermabond Advanced was the strongest and
      most flexible, set in the shortest time, and was a fairly viscous adhesive, all
      of which are clinically desirable characteristics.

PMID- 23167861
TI  - Rural clinical experiences for emergency medicine residents: a curriculum
      template.
AB  - Rural emergency departments (EDs) in the United States are less likely to be
      staffed with emergency medicine (EM) residency-trained and American Board of
      Emergency Medicine (ABEM)-certified physicians than urban EDs. Rural EM clinical
      experiences during residency training have been suggested as a strategy to
      encourage future rural practice, but past Accreditation Council for Graduate
      Medical Education (ACGME) Residency Review Committee for Emergency Medicine
      program requirements and a lack of familiarity with rural rotations in the EM
      graduate medical education (GME) community have limited their availability. To
      provide a template for the development and implementation of a rural EM clinical
      experience, Kern's six-step approach was followed.

PMID- 23167862
TI  - Contrast-induced nephropathy: doubts and certainties.

PMID- 23167863
TI  - Measuring the measurable: a commentary on impact factor.

PMID- 23167864
TI  - A model for emergency department end-of-life communications after acute
      devastating events--part II: moving from resuscitative to end-of-life or
      palliative treatment.
AB  - The model for emergency department (ED) end-of-life communications after acute
      devastating events addresses decision-making capacity, surrogates, and advance
      directives, including legal definitions and application of these steps. Part II
      concerns communications moving from resuscitative to palliative and end-of-life
      treatments. After completing the steps involved in determining decision-making,
      emergency physicians (EPs) should consider starting palliative measures versus
      continuing resuscitative treatment. As communications related to these end-of
      life decisions increasingly fall within the scope of emergency medicine (EM)
      practice, we need to become educated about and comfortable with them.

PMID- 23167865
TI  - Assessing the influence of insulation on intravenous fluid infusion temperature.
AB  - OBJECTIVES: Inducing therapeutic hypothermia using chilled saline in resuscitated
      cardiac arrest patients has been shown to be feasible and effective. Limited
      research exists assessing the efficiency of this cooling method. The objective of
      this study was to assess the change in temperature of 4 degrees C saline upon
      exiting an infusion set in the laboratory setting while varying conditions of
      fluid delivery. METHODS: Efficiency was studied by assessing change in fluid
      temperature ( degrees C) during the infusion under four laboratory conditions.
      Each condition was performed four times using 1-L bags of normal saline. Fluid
      was infused into a 1000-mL beaker through 10 gtt/mL tubing. Flow rate was
      controlled using a tubing clamp and in-line transducer with a flow meter, while
      temperature was continuously monitored in a side port at the terminal end of the
      intravenous (IV) tubing using a digital thermometer. The four conditions included
      different insulation methods. Descriptive statistics and analysis of variance
      were performed to assess changes in fluid temperature. RESULTS: The mean (+/-SD)
      fluid temperature at time 0 was 3.2 degrees C (95% confidence interval [CI] = 3.0
      to 3.4  degrees C) with no significant difference in starting temperature between
      groups (p = 0.45). When flow rate was constant, it was determined that fluid
      temperatures were significantly cooler when infused using a chilled, gel-filled
      sleeve around the saline bag (p < 0.006). CONCLUSIONS: In a laboratory setting,
      the most efficient method of infusing cold fluid appears to be a method that both
      keeps the bag of fluid insulated and infused at a faster rate.

PMID- 23167866
TI  - Clinical decision rules to improve adverse drug events.

PMID- 23167870
TI  - Regio- and stereoselective synthesis of a library of bioactive dispiro
      oxindolo/acenaphthoquino andrographolides via 1,3-dipolar cycloaddition reaction
      under microwave irradiation.
AB  - Dispiro-pyrrolidino/pyrrolizidino fused oxindoles/acenaphthoquinones have been
      derived from andrographolide via azomethine ylide cycloaddition to the conjugated
      double-bond under microwave (MW) irradiation. The reactions are chemo-, stereo-,
      and regioselective in nature. Change in amino acid from sarcosine/N-benzyl
      glycine to l-proline changes the regiochemistry. A representative library of 40
      compounds along with in vitro anticancer evaluation is reported. 

PMID- 23167871
TI  - Are cats and dogs the major source of endotoxin in homes?
AB  - Previous studies have suggested that exposure to cats and dogs during early
      childhood reduces the risk of allergic disease, possibly by increasing home
      endotoxin exposure. This study asked the question of whether cats and dogs are
      the dominant influence on dust endotoxin concentrations in homes after
      considering other variables reportedly associated with endotoxin. The presence of
      cats or dogs in homes, household and home characteristics, and dust endotoxin
      concentrations from 5 locations were assessed in 966 urban and suburban homes.
      Whether considered together as pets or as cats and dogs separately, the presence
      of cats and dogs significantly contributed to living room and bedroom floor
      endotoxin concentrations, but not to bed endotoxin concentrations. However, the
      two variables consistently related to endotoxin in all home sites were the home
      occupant density (occupants/room) and cleanliness of the home. Our data suggest
      that reducing occupant density and improving home cleanliness would reduce home
      endotoxin concentrations more than removing pet cats or dogs from the home.
      PRACTICAL IMPLICATIONS: Many studies have shown that early childhood exposure to
      indoor cats or dogs is associated with a reduced risk of later allergic disease
      and asthma. An important question is whether alteration in allergic risk
      associated with cat and dog exposure results from increased endotoxin exposure or
      from some other associated exposure. Our findings show that cats and dogs are not
      the dominant source of endotoxin in homes; rather, the density of human
      occupation and poor cleaning contribute more consistently to higher home
      endotoxin concentrations especially in the beds.

PMID- 23167872
TI  - Prevalence of the E318K MITF germline mutation in Italian melanoma patients:
      associations with histological subtypes and family cancer history.
AB  - A French and an Australian study have recently identified a rare germline
      functional variant in the microphthalmia-associated transcription factor (MITF)
      (E318K) that predisposes to familial and sporadic melanoma and to renal cell
      carcinoma (RCC), showing a new link between two tumour types with different risk
      factors and between deregulated sumoylation and cancer. The aim of this study was
      to test the prevalence of the MITF E318K mutation in 667 Italian melanoma
      patients. We observed significant associations between histological subtypes and
      family cancer history. Carriers exhibited a nearly threefold higher risk of
      developing melanoma compared with controls. Carriers were also more likely to
      have developed multiple primary melanomas (6.40-fold), compared with wt patients.
      Carriers with a personal and/or family history of pancreatic cancer and kidney
      cancer had a nearly 31- and eightfold higher risk of developing melanoma compared
      with wt patients. Our findings further support MITF as a medium-penetrance
      melanoma susceptibility gene, highlight a potential association with histological
      subtypes and suggest that MITF may predispose to pancreatic cancer.

PMID- 23167873
TI  - Cross-cultural adaptation and linguistic validation of age-group-specific
      haemophilia patient-reported outcome (PRO) instruments for patients and parents.
AB  - Currently, haemophilia care aims to provide the best possible quality of life for
      individuals living with this chronic disease. Many factors are known to influence
      treatment adherence, including treatment satisfaction. Health-related quality of
      life (HRQoL) and treatment satisfaction are, therefore, important outcomes in
      clinical trials and clinical practice. As individuals' perception of their well
      being often differs from that of their physician, it is recommended that self
      report instruments are used to assess patient-reported outcomes (PROs). The way
      that the impact of haemophilia is perceived by the patient and their family can
      be different, so it is important to assess how parents perceive the impact on
      their children. A series of PRO instruments have been developed, adapted to
      different age groups and parents of patients with haemophilia. To allow the
      instruments to be used internationally, culturally adapted and linguistically
      validated translations have been developed; some instruments have been translated
      into 61 languages. Here, we report the process used for cultural adaptation of
      the Haemo-QoL, Haem-A-QoL and Hemo-Sat into 28 languages. Equivalent concepts for
      22 items that were difficult to adapt culturally for particular languages were
      identified and classed as semantic/conceptual (17 items), cultural (three items),
      idiomatic (one item), and grammatical (one item) problems. This has resulted in
      linguistically validated versions of these instruments, which can be used to
      assess HRQoL and treatment satisfaction in clinical trials and clinical practice.
      They will provide new insights into areas of haemophilia that remain poorly
      understood today.

PMID- 23167874
TI  - Ethics, publication and The Clinical Teacher.

PMID- 23167875
TI  - Time to teach (to teach).

PMID- 23167876
TI  - Developing the One-Minute Preceptor.
AB  - BACKGROUND: Learning from experienced doctors in real clinical settings is very
      important for medical students. However, the busy and at times unpredictable
      nature of clinical work means that clinical work must take priority over
      teaching. What clinicians want is to be able to offer quality learning
      experiences for students without significant disruption to their clinical work.
      CONTEXT: In the context of medical education, students are learning in a variety
      of physical locations. These various locations require different sets of teaching
      skills. This article describes how as faculty educational developers we worked
      with clinicians to enhance their role as teachers within busy clinical contexts.
      More specifically, we will describe how we augmented an established programme of
      travelling workshops for clinical teachers by incorporating the key principles
      associated with the development of the One-Minute Preceptor. INNOVATION AND
      IMPLICATIONS: We combined classroom training with observation of teaching in the
      clinical area, and by doing so were more able to translate classroom theory into
      authentic workplace practice.

PMID- 23167877
TI  - Transforming teaching into scholarship.
AB  - BACKGROUND: Traditionally, scholarship has been defined very narrowly as the
      number of one's publications and grant awards. Recently this definition has
      broadened to include dissemination of knowledge, experience or a tangible product
      shared with the educational community. CONTEXT: In an effort to enhance our own
      educational development, in 2005 we formed a 'community of practice' centred on
      teaching. The group was formed to share ideas, to reflect on teaching experiences
      and to transmit new knowledge to other clinician-educators within our paediatrics
      department. INNOVATION: By examining what we do as clinicians and teachers, we
      were able to gather information about how we teach and how our students learn. As
      we reflected on this information within our small learning community, we began to
      realise the value of other people's input as a great source of learning. One of
      our first activities as a community was to develop a series of conferences on
      clinical teaching. We also asked ourselves how we could transform what we were
      doing into educational scholarship. It occurred to us that the conference topics
      could be the chapters of a book. Therefore, we chose to create a handbook that
      was a 'learning journal' on teaching. IMPLICATIONS: We transformed the initial
      list of conference topics to scholarship by using a three-phase model for
      transforming teaching into scholarship. Using this framework, we have
      demonstrated how clinician-educators can transform teaching activities into
      scholarship, and how important a community of practice can be for professional
      development.

PMID- 23167878
TI  - Teaching child development to medical students.
AB  - PURPOSE: Several published strategies on teaching the screening of normal child
      development were integrated into a small group learning experience for second
      year medical students to address practical and logistical problems of approaches
      used individually. This study examines the effectiveness of this integrated
      approach using student evaluations. METHOD: A total of 191 second-year university
      medical and dental students were invited to participate. Well-described learning
      objectives, the Ages and Stages Questionnaire (ASQ), live parent-child dyads and
      video backup were used. Students rotated through three small group stations.
      Feedback was provided using a Likert scale (from 1, low, to 5, high) and written
      comments. Consent was obtained. Live parent-child dyads versus video clip groups
      were analysed by averaging overall scores. Generalised estimating equation (GEE)
      analysis in stata (Stata Corporation, College Station, Texas) was used for
      comparing the two groups. RESULTS: A total of 178 students (93%) agreed to
      participate and filled out the evaluation forms. The overall score on the Likert
      scale was 4.6 (range 4-5). On two occasions video clips were substituted for live
      parent-child dyad presentations in one of the three stations. These students
      (n=43, rating 4.61/5) rated their experience as comparable with those who had
      three live family stations (n=135, rating 4.56/5). Student comments were grouped
      into broad themes, with most being positive about their learning experience.
      CONCLUSIONS: This integrated approach is highly acceptable. Video clip usage,
      live dyads, clear written objectives and use of a standardised screening tool
      preserved the interaction and immediacy of a clinical encounter, while
      maintaining consistency in content.

PMID- 23167879
TI  - Emergency telephone consultations: a new course for medical students.
AB  - BACKGROUND: Using the telephone for consultations is now common practice.
      Although there is a clear need for specific training for telephone consultations,
      it is uncommon for it to be taught in medical school. METHODS: A practical course
      on emergency telephone consultations (ECTs) was designed for the medical degree
      course at the University of Bern Medical School. During the module, each of the
      volunteer fifth-year medical students had to perform two simulated telephone
      consultations. Medical students in their first year of medical school acted as
      simulated patients (SPs), and they gave immediate feedback to the participants.
      RESULTS: Nineteen per cent of fifth-year students voluntarily undertook the ETC
      course. The course was rated 'very informative' by 68 per cent of the
      participants, and 'informative' by 32 per cent. Ninety-four per cent of the
      attendees recorded a personal learning gain, and 68 per cent suggested that the
      course should be obligatory. All the participants thought that the SPs played
      their roles realistically. DISCUSSION: In their rating of the ETC, the fifth-year
      students gave it a mean mark of 5.5 (out of a maximum of 6), suggesting that they
      thought it had been very successful. Students became aware of their need for ETC
      training through the course itself, and they recommended that it should be
      obligatory. The ETC pilot received a highly positive response from lead
      clinicians who anticipated a rising number of telephone consultations, and who
      have to deal with trainees who have not been taught about how to deal with ETCs.
      As a result, the Faculty of Medicine decided to make the course obligatory.

PMID- 23167880
TI  - A patient safety course for preclinical medical students.
AB  - BACKGROUND: We developed a course to introduce incoming third-year medical
      students to the subject of patient safety, to focus their attention on teamwork
      and communication, and to create an awareness of patient-safe practices that will
      positively impact their performance as clinicians. METHODS: The course, held
      prior to the start of clinical rotations, consisted of lectures, web-based
      didactic materials, small group activities and simulation exercises, with an
      emphasis on experiential learning. First, students inspected a 'room of horrors',
      which is a simulated clinical environment riddled with errors. Second, we used
      lenticular puzzles in small groups to elicit teamwork behaviours that parallel
      real-life interactions in health care. Each team was given 8 minutes to complete
      a 48-piece puzzle, with five pieces removed at random and given to other teams.
      The salient teaching point of this exercise is that for a team to complete the
      task, team members must communicate with members of their own team as well as
      with other teams. Last, simulation scenarios provided a clinical context to
      reinforce the skills introduced through the puzzle exercise and lectures. The
      students were split into groups of six or seven members and challenged with two
      scenarios. Both scenarios focused on a 56-year-old man in respiratory distress.
      The teams were debriefed on both clinical management and teamwork. RESULTS: The
      vast majority of the students (93%) agreed that the course improved their patient
      safety knowledge and skills. DISCUSSION: The positive response from students to
      the introductory course is an important step in fostering a culture of patient
      safety.

PMID- 23167881
TI  - Keeping it real! Enhancing realism in standardised patient OSCE stations.
AB  - BACKGROUND: Objective structured clinical examinations (OSCEs) are a commonly
      used method of assessing clinical competency in health care education. They can
      provide an opportunity to observe candidates interacting with patients. There are
      many challenges in using real patients in OSCEs, and increasingly standardised
      patients are being used as a preference. However, by using standardised patients
      there is a risk of making the encounter artificial and removed from actual
      clinical practice. CONTEXT: Efforts made in terms of cognitive, auditory, visual,
      tactile, psychological and emotional cues can minimise the differences between a
      simulated and real clinical scenario. However, a number of factors, including
      feasibility, cost and usability, need to be considered if such techniques are to
      be practicable within an OSCE framework. INNOVATION: This article describes a
      series of techniques that have been used in our institution to enhance the
      realism of a standardised patient encounter in an OSCE. Efforts in preparing
      standardised patient roles, and how they portray these roles, will be considered.
      A wide variety of equipment can also be used in combination with a patient and
      the surrounding environment, which can further enhance the authenticity of the
      simulated scenario. IMPLICATIONS: By enhancing the realism in simulated patient
      OSCE encounters, there is potential to trigger more authentic conscious responses
      from candidates and implicit reactions that the candidates themselves may be less
      aware of. Furthermore, using such techniques may allow faculty members to select
      scenarios that were previously not thought possible in an OSCE.

PMID- 23167882
TI  - Man versus machine: the preferred modality.
AB  - BACKGROUND: When learning objectives do not specifically dictate the use of one
      simulation modality over another, we sought to answer the question of which
      modality is preferred. We also assessed the impact of debriefing, and the
      frequency of participants asserting their leadership, as well as self-reported
      comfort and competence, and the ability to generate differential diagnoses when
      either a standardised patient (SP) or high-technology simulator (HTS) was used.
      METHODS: One hundred and forty medical students participated in a simulation
      based activity focusing on teamwork, task delegation, role clarity and effective
      communication. Two similar clinical scenarios were presented, and either an HTS
      or an SP was used. Following each scenario, participants were surveyed on the
      realism of the simulation and the patient, and also on their self-assessed
      comfort and competence. They were also asked to indicate which role they played,
      to list possible differential diagnoses for the case and, following the second
      scenario, which modality they preferred. RESULTS: The surveys indicated that 91
      per cent (127) of students preferred the SP. The perceived realism of the
      simulation was higher for the second scenario than for the first. Scenarios with
      an SP were found to be significantly more realistic than the scenarios where the
      HTS was used. Comfort and competence scores were higher following the second
      scenario. No differences in the ability of participants to generate a list of
      differentials were found, and nearly twice as many participants reported taking
      the leadership role during their second simulation. DISCUSSION: We have found low
      and high technology to have similar effectiveness for achieving learning
      objectives and for the demonstration of skills; however, students clearly
      preferred the SPs.

PMID- 23167883
TI  - Models for enhancing competency-based training and contextual clinical decision
      making.
AB  - BACKGROUND: In the era of quality care, competency and outcome-based education,
      new models of teaching and resident staff training are greatly needed. These
      should be based on adult learning principles and allow for high-quality, patient
      centred, evidence-based care. CONTEXT: Three areas that need restructuring with
      specific conceptual frameworks to allow for seamless competency-based training,
      and also to assist in putting the decision-making process in context, are: case
      or topic presentation; diagnostic labelling; and immediate interventions for
      front-line caregivers. INNOVATION: Three models are proposed: the competency
      structured presentation (CSP) model; the bedside clinical diagnosis, etiological
      cause and severity score diagnostic labelling (BESD) model; and the symptomatic,
      supportive, specific, specialty and site of care (5S) model. IMPLICATIONS: The
      models listed above may assist in the following domains of patient care. In a
      competency-structured presentation, the CSP model formalises case presentations
      and discussions in a competency-based structure, thereby supporting the
      development of a competency-focused thought process for patient care. The BESD
      and 5S models improve the understanding of patient problems within the
      appropriate context, and thus assists in achieving the following quality
      outcomes. The BESD model promotes better diagnostic labelling, thereby assisting
      in implementing individualised, evidence-based interventions. The 5S model
      promotes the cognitive conceptualisation of medical management, which will aid a
      more comprehensive, patient-centred, multidisciplinary care input, thereby
      reducing process errors and improving outcomes.

PMID- 23167884
TI  - The experience of interdisciplinary peer-assisted learning (PAL).
AB  - BACKGROUND: The importance and benefits of interdisciplinary practice in health
      care have been well documented. Despite this, few medical schools have developed
      formal curriculum opportunities for interdisciplinary teaching. Here, as an
      example of medical and nursing students teaching and learning together, we
      describe a novel approach to interdisciplinary peer-assisted learning led by
      students on fluid and electrolyte balance. METHODS: Teaching sessions were
      developed and led by a collaborative group of fourth-year medical and nursing
      students, under the supervision of teaching staff. Each session had different
      stations aimed at encouraging interdisciplinary discussion between students. A
      pre- and post-event questionnaire was used to determine students' views on
      interdisciplinary learning and teaching. RESULTS: All students felt that they
      benefited from the interdisciplinary format of the sessions, and would recommend
      the sessions to other students. Furthermore, both nursing and medical students
      reported improvements in their confidence relating to several key domains of
      managing fluid balance. DISCUSSION: The sessions described provide opportunities
      for collaboration between medical and nursing students in the planning and
      delivery of teaching sessions. There are doubtless many other ways in which such
      interdisciplinary learning could occur, but to date very few have been described
      in the literature. This example is offered to encourage others to experiment in
      this important area, to share their experiences and approaches, and to stimulate
      further debate on the place of interdisciplinary learning and working in
      undergraduate health care curricula.

PMID- 23167885
TI  - Data protection training improves data handling.
AB  - BACKGROUND: Clinicians are required by law to keep personal patient data secure.
      Data protection training (DPT) has been suggested to educate medical
      professionals in how to most appropriately manage such information. METHODS:
      Information regarding the handling, storage and disposal of patient information
      and prevalence of DPT was gathered using anonymous questionnaires. RESULTS: The
      vast majority of doctors (98.6%) handle patient lists containing patient
      sensitive information: 15.8 per cent used general waste bins for the disposal of
      lists and 57.3 per cent removed printed patient lists from hospital premises;
      43.3 per cent of doctors had received DPT. A significantly greater proportion of
      consultants have received DPT, compared with doctors in training. Doctors who
      have received DPT were less likely to take patient lists away from a hospital
      site (p=0.011). DPT led to a trend towards increased awareness of the security of
      the storage location of their patient lists and of trust policy regarding the use
      of personal USB devices. DISCUSSION: With the expansion of patient data
      collection and storage, it is important for doctors to maintain an awareness of
      how to handle such data. DPT is not currently common practice. Our study suggests
      positive benefits from DPT, and we suggest it could improve the safety with which
      patient data is handled.

PMID- 23167886
TI  - Surgical training in your hands: organising a skills course.
AB  - BACKGROUND: The advent of simulated surgical skills courses has brought dynamic
      changes to the traditional approach to acquiring practical skills in surgery.
      CONTEXT: Teaching is a core part of the surgical profession, and any trainee can
      be involved in the organisation of skills training courses. This paper outlines
      the importance of organising surgical skills courses for trainees, and provides a
      practical guide on how to do so within busy clinical environments. INNOVATION:
      The paper examines how to plan a course, how to design the programme, and
      provides tips on faculty staff requirements, venue, finance and participants,
      with additional suggestions for assessment and evaluation. IMPLICATIONS: We
      recommend the organisation of skills courses to any trainee. By following key
      ground rules, the surgical trainee can enable the acquisition of advanced
      learning opportunities and the ability to demonstrate valuable organisational
      skills.

PMID- 23167887
TI  - Challenges of the transition from student to educator.

PMID- 23167888
TI  - Surgical induction courses: a junior trainee's perspective.

PMID- 23167897
TI  - Using the term 'essential hypertension'.

PMID- 23167896
TI  - Fixing a peer-led teaching day into the calendar.

PMID- 23167898
TI  - Undergraduate presentation-based assessments.

PMID- 23167899
TI  - Regulation of synaptic currents by mGluR2 at reciprocal synapses in the mouse
      accessory olfactory bulb.
AB  - The throughput of information from the accessory olfactory bulb (AOB) to
      downstream structures is controlled by reciprocal dendrodendritic inhibition of
      mitral cells by granule cells. Given the high expression levels of mGluR2, a
      metabotropic glutamate receptor, in the AOB and the fact that the activation of
      mGluR2 permits the formation of a specific olfactory memory, we reasoned that
      mGluR2 might play an important role in regulating dendrodendritic inhibition. To
      test this hypothesis, we examined the effects of pharmacological and genetic
      manipulations of mGluR2 on synaptic responses measured from mitral or granule
      cells in slice preparations from 23- to 36-day-old Balb/c mice. To evoke
      dendrodendritic inhibition, a depolarizing voltage step from -70 to 0 mV or a
      threshold current stimulus adjusted to elicit action potential(s) was applied to
      a mitral cell using either a nystatin-perforated or conventional whole-cell
      configuration. We found that an agonist for group II metabotropic glutamate
      receptors (mGluR2/mGluR3), DCG-IV [(2S,1'R,2'R,3'R)-2-(2,3
      dicarboxycyclopropyl)glycine], suppressed, whereas the mGluR2/mGluR3 antagonist
      LY341495 [(alphaS)-alpha-amino-alpha-[(1S,2S)-2-carboxycyclopropyl]-9H-xanthine-9
      propanoic acid] enhanced dendrodendritic inhibition. Genetic ablation of mGluR2
      markedly impaired the effects of DCG-IV and LY341495 on dendrodendritic
      inhibition. DCG-IV reduced both the frequency and the amplitude of spontaneous
      miniature excitatory postsynaptic currents recorded from granule cells.
      Additionally, DCG-IV inhibited high-voltage-activated calcium currents in both
      mitral and granule cells. These results suggest that mGluR2 reduces
      dendrodendritic inhibition by inhibiting synaptic transmission between mitral
      cells and granule cells in the AOB.

PMID- 23167900
TI  - Pornographic picture processing interferes with working memory performance.
AB  - Some individuals report problems during and after Internet sex engagement, such
      as missing sleep and forgetting appointments, which are associated with negative
      life consequences. One mechanism potentially leading to these kinds of problems
      is that sexual arousal during Internet sex might interfere with working memory
      (WM) capacity, resulting in a neglect of relevant environmental information and
      therefore disadvantageous decision making. In this study, 28 healthy individuals
      performed 4 experimental manipulations of a pictorial 4-back WM task with
      neutral, negative, positive, or pornographic stimuli. Participants also rated 100
      pornographic pictures with respect to sexual arousal and indicated masturbation
      urges previous to and following pornographic picture presentation. Results
      revealed worse WM performance in the pornographic picture condition of the 4-back
      task compared with the three remaining picture conditions. Furthermore,
      hierarchical regression analysis indicated an explanation of variance of the
      sensitivity in the pornographic picture condition by the subjective rating of the
      pornographic pictures as well as by a moderation effect of masturbation urges.
      Results contribute to the view that indicators of sexual arousal due to
      pornographic picture processing interfere with WM performance. Findings are
      discussed with respect to Internet sex addiction because WM interference by
      addiction-related cues is well known from substance dependencies. 

PMID- 23167901
TI  - Caffeine induces CYP1A2 expression in rat hepatocytes but not in human
      hepatocytes.
AB  - Caffeine is the active constituent in coffee. Continual consumption of caffeine
      can lead to an attenuated response also known as tolerance. Results from rat
      studies have shown that caffeine is an inducer of CYP1A2, the enzyme responsible
      for caffeine's metabolism. This suggests that CYP1A2 induction by caffeine may be
      in part responsible for caffeine tolerance. However, whether caffeine induces
      CYP1A2 expression in humans remains unknown. Our results from luciferase assays
      performed in HepG2 cells showed that caffeine is not an activator of the aromatic
      hydrocarbon receptor (AhR), a major transcription factor involved in upregulation
      of CYP1A2. Furthermore, caffeine did not induce CYP1A2 expression in primary
      human hepatocytes at a concentration attained by ordinary coffee drinking. On the
      other hand, caffeine enhanced CYP1A2 expression by 9-fold in rat hepatocytes. Our
      results suggest that caffeine from ordinary coffee drinking does not induce
      CYP1A2 expression in humans and that factors other than CYP1A2 induction by
      caffeine likely contribute to development of caffeine tolerance in humans.

PMID- 23167902
TI  - Exploring slime mould diversity in high-altitude forests and grasslands by
      environmental RNA analysis.
AB  - In spite of the ecological importance of protists, very little data is available
      on their distribution in soil. This investigation is the first of its kind on
      what could be the major components of the soil protistan community, the
      Myxomycetes, or plasmodial slime-moulds, a monophyletic class in the phylum
      Amoebozoa. Myxomycetes have a complex life cycle culminating in the formation of
      mainly macroscopic fruiting bodies, highly variable in shape and colour, which
      can be found in every terrestrial biome. Despite their prevalence, they are
      paradoxically absent from environmental DNA sampling studies. We obtained
      myxomycete SSU rRNA gene sequences from soil-extracted RNAs using specific
      primers. Soil samples were collected in three mountain ranges (France, Scotland
      and Japan). Our study revealed an unexpectedly high diversity of dark-spored
      Myxomycetes, with the recovery of 74 phylotypes. Of these, 74% had < 98% identity
      with known sequences, showing a hidden diversity; there was little overlap
      between localities, implying biogeographical patterns. Few phylotypes were
      dominant and many were unique, consistent with the 'rare biosphere' phenomenon.
      Our study provides the first detailed insight into the community composition of
      this ecologically important group of protists, establishing means for future
      studies of their distribution, abundance and ecology.

PMID- 23167903
TI  - S-nitrosylation of Ras in breast cancer.
AB  - Elevated expression of nitric oxide synthase 2 has been recently shown to
      correlate with poor survival in estrogen receptor-negative breast cancer. In an
      article in Breast Cancer Research, Switzer and colleagues identify the
      transcription factor Ets-1 as a critical mediator of nitric oxide-dependent
      oncogenic gene expression in basal-like breast cancer. This pathway is driven by
      S-nitrosylation of wild-type Ras, which leads to mitogen-activated protein kinase
      dependent phosphorylation and activation of Ets-1. These results establish a new
      role for S-nitrosylation in mediating an aggressive breast cancer phenotype. 

PMID- 23167904
TI  - Analytical figures of merit for partial least-squares coupled to residual
      multilinearization.
AB  - A new expression is developed which allows estimating the sensitivity for the
      whole family of multivariate calibration algorithms based on partial least
      squares regression combined with residual multilinearization. The sensitivity can
      be employed to compute other relevant figures of merit such as analytical
      sensitivity, limit of detection, limit of quantitation, and uncertainty in
      predicted concentration. The results are substantiated by extensive Monte Carlo
      noise addition simulations for a variety of systems with a different number of
      analytes and interfering agents, different degrees of overlapping in component
      profiles, and different numbers of instrumental data modes per sample, all
      requiring the achievement of the second-order advantage. The connection between
      the present approach and the intuitive concept of net analyte signal is
      discussed. An experimental example for which second-, third-, and fourth-order
      data are available is also studied, concerning the improvement in figures of
      merit on increasing the data order, which is consistent with the decrease in
      average prediction error.

PMID- 23167905
TI  - Frequency of self-adjustment of insulin dose and metabolic control in Type 2
      diabetes -is there an association?
AB  - AIM: To investigate the supposition that self-adjustment of insulin dose will
      improve metabolic control in patients with Type 2 diabetes. METHODS: The number
      of self-adjustments of insulin dose was checked in a cross-sectional study
      involving 300 patients with Type 2 diabetes in a university outpatient
      department, who were insulin treated. RESULTS: One hundred and ninety-three
      patients (64%) performed insulin dose adjustments at least once in 14 days. The
      mean number of dose adjustments was 17.4 per 14 days. Patients with self
      adjustments of insulin dose were younger (65.6 vs. 68.9 years), had a higher
      social status score (11.1 vs. 9.8) and a higher insulin dose (68.8 vs. 53.6
      IU/day) than patients without dose adjustments. Each insulin dose adjustment was
      associated with an HbA(1c) decrease of 0.016% (P = 0.004). Any additional blood
      glucose self measurement was associated with an HbA(1c) increase of 0.019% (P =
      0.038). CONCLUSIONS: Two-thirds of patients with Type 2 diabetes, who have
      undergone training in how to manage their condition, practise insulin dose self
      adjustments. A weak association was observed between insulin dose adjustments and
      HbA(1c).

PMID- 23167906
TI  - A questionnaire-based survey to assess patient satisfaction, ease-of-learning,
      ease-of-use, injection site pain and overall patient satisfaction of the
      follitropin-alpha (Gonal-f) filled-by-mass (FbM) prefilled pen compared with
      other systems of gonadotrophin administration.
AB  - BACKGROUND: Gonadotrophins are used routinely for follicular stimulation during
      ovarian induction and assisted reproduction techniques. Developments in
      recombinant follicle-stimulating hormone preparations and their injection devices
      have improved patient quality of life by enabling patients to self-administer
      treatment at home. The objective of this study was to investigate patient
      experiences of learning to use and overall satisfaction with the follitropin
      alpha (Gonal-f) filled-by-mass (FbM) prefilled pen. METHODS: This questionnaire
      based survey study was conducted in 23 fertility centres in Japan over a period
      of 14 months. Patients who were receiving fertility treatment with the
      follitropin-alpha (FbM) prefilled pen were asked to complete a questionnaire to
      assess their satisfaction, ease of learning and use, and injection site pain
      following treatment. RESULTS: A total of 663 women participated in the study. The
      majority of patients found the instructions for administering follitropin-alpha
      with the prefilled pen easy to understand (83.0%; n = 546/658) and patients found
      that a hands-on demonstration by a nurse or doctor was the most useful tool for
      learning to use the follitropin-alpha (FbM) prefilled pen (80.0%; n = 497/621).
      Forty-eight percent (n = 318) of patients in the study had previous experience
      with different types of fertility medications and the majority of these patients
      found the follitropin-alpha (FbM) prefilled pen easier to use (75.1%; n =
      232/309) and less painful (89.0%; n = 347/390) than their previous medication.
      The majority (80.2%; n = 521/650) of patients reported overall satisfaction with
      the follitropin-alpha (FbM) prefilled pen. CONCLUSIONS: The follitropin-alpha
      (FbM) prefilled pen is an easy-to-use injection device according to this
      questionnaire-based survey. Patients who had experience of different types of
      fertility medication preferred the follitropin-alpha (FbM) prefilled pen to other
      injection devices.

PMID- 23167907
TI  - The effects of calcium hydroxide removal methods on bond strength of Epiphany SE
      with two irrigation protocols.
AB  - OBJECTIVE: The purpose of this study was to compare the effects of five calcium
      hydroxide removal methods on the bond strength of Epiphany SE sealer after canal
      irrigation with NaOCl+EDTA or NaOCl+MTAD. MATERIALS AND METHODS: The 120 roots
      were instrumented by using the ProTaper rotary system under irrigation with 2.5%
      sodium hypochlorite and randomly divided into two major groups according to the
      final irrigation: 1.3% NaOCl + MTAD and 5% NaOCl + 17% EDTA. For controls, 10
      roots from each of the final irrigations with NaOCl + MTAD and NaOCl + EDTA (20
      roots) were not filled with Ca(OH)2. The intra-canal paste, Ca(OH)2 was applied
      to each of the 100 remaining roots and stored at 37 degrees C for 7 days. Each
      group was sub-divided into five sub-groups (n = 10) according to the removal
      technique for the intra-canal dressing: Group-1: recapitulation with size 30 K
      file + 3 ml of saline solution, Group-2: recapitulation with size 30 K file + 3
      ml of 5% NaOCl, Group-3: using 5% NaOCl + 17% EDTA, Group-4: using 5%NaOCl + 15%
      citric acid, and Group-5: using 1.3% NaOCl + 5 ml MTAD. The root canals were
      filled with Resilon and Epiphany SE sealer. The bond strength was measured.
      RESULTS: The mean bond strength of Epiphany SE to root dentine irrigated with
      NaOCl + MTAD was lower than that of NaOCl + EDTA. The highest bond strengths were
      3.31 +/- 0.057 and 2.60 +/- 0.054 in the NaOCl + citric acid group when Ca(OH)2
      was applied to roots treated with NaOCl + EDTA and NaOCl + MTAD, respectively (p
      < 0.05). CONCLUSION: For root canals treated with NaOCl + EDTA or NaOCl + MTAD,
      the use of NaOCl + chelating agent for Ca(OH)2 removal does not adversely affect
      the bond strength of Epiphany SE to dentin.

PMID- 23167908
TI  - Saliva in relation to dental erosion before and after radiotherapy.
AB  - OBJECTIVE: Low saliva flow and abnormal saliva composition are common conditions
      after radiotherapy for oral cavity and pharyngeal cancer. Both conditions
      increase the susceptibility to dental caries and erosion, which may be further
      accelerated by changes in food preferences. The aim of this study was to
      determine changes in saliva flow and susceptibility to erosive challenges in
      pharyngeal cancer patients before and after radiotherapy to the head and neck.
      MATERIALS AND METHODS: The erosive potential of sucking acidic candies with and
      without calcium was determined in nine patients (50-68 years) before and after
      receiving a radiation dose of 66 Gy to the head and neck area. The erosive
      potential was evaluated from saliva degree of saturation with respect to
      hydroxyapatite (HAp) and by dissolution of HAp in candy-stimulated saliva.
      RESULTS: Sucking acidic candies increased saliva flow rates ~ 17-fold before as
      well as after radiotherapy (p < 0.001). However, significantly lower unstimulated
      (p < 0.05) and stimulated (p < 0.01) saliva flow rates were obtained after
      radiotherapy. Also, saliva became more under-saturated with respect to HAp during
      (p < 0.01) and in a period after sucking the candies (p < 0.01). HAp dissolution
      was significantly lower with the candy containing calcium compared with the
      control candy, both before and after radiotherapy (p < 0.001 and p < 0.05).
      CONCLUSIONS: Radiotherapy to the head and neck area significantly reduced saliva
      flow and altered saliva composition in a way that may increase the susceptibility
      to dental disease. However, saliva could be stimulated by acidic candies, which
      could be made nearly non-erosive even in irradiated patients.

PMID- 23167909
TI  - Systolic and diastolic ventricular function assessed by tissue Doppler imaging in
      children with chronic kidney disease.
AB  - Chronic kidney disease (CKD) is associated with elevated cardiovascular risk even
      during childhood. Tissue Doppler is a sensitive technique for the assessment of
      ventricular dysfunction with relatively little data available in children with
      CKD. We report a prospective cross-sectional echocardiographic study at a
      tertiary center. Forty-nine patients with median (range) age 11.2 years (6.9
      17.9), weight 39.6 kg (23.6-99.7) and height 146 cm (122-185). Thirty-one
      patients were male. Median duration of follow-up for CKD was 7.1 years (range
      0.13-16.9). Patients were in CKD stage 3 (n = 37) or 4 (n = 12). Mitral valve E
      wave, A-wave, and E/A ratio showed mean (SD) z-scores of 0.08 (0.93), 0.12 (0.82)
      and -0.13 (0.84), respectively. Tissue Doppler imaging (TDI) at the lateral
      mitral valve annulus showed e', a', s', and E/e' z-scores mean (SD) -1.10 (0.76),
      -0.29 (0.92), -1.2 (0.7), and 0.86 (1.1), respectively. There was a significant
      negative correlation of e' and s' z-score with patient age. E/e' ratio correlated
      positively with patient age. Blood pressure, left ventricular mass, and relative
      wall thickness did not correlate with tissue Doppler measurements. The e' and s'
      velocities correlated significantly with each other, suggesting an interaction of
      systolic and diastolic dysfunction. Children with CKD may have abnormalities of
      systolic and diastolic ventricular function on TDI, which are not evident on
      blood pool Doppler. The tissue Doppler results are consistent with worsening
      ventricular function in older patients.

PMID- 23167910
TI  - Parents' views on child physical activity and their implications for physical
      activity parenting interventions: a qualitative study.
AB  - BACKGROUND: Establishing healthy physical activity (PA) behaviours in early
      childhood is important for future PA behaviours. Parents play a central role in
      young children's PA. However, there is currently little research on parenting
      interventions to increase child PA. This study was formative work to inform the
      content of a pilot randomised-controlled trial. METHODS: In-depth telephone
      interviews were carried out with 32 parents of 6 to 8 year old children residing
      in two areas that varied in their socio-economic characteristics, in Bristol, UK.
      Data were analysed thematically using a framework approach. RESULTS: Most parents
      described their child as being active or very active and indicated that they did
      not perceive a need for an increase in their child's PA. Parents used a variety
      of visual cues to make this judgement, the most common being that they perceived
      their child as having lots of energy or that they did not view them as
      overweight. Parents reported environmental factors such as monetary cost, time
      constraints, lack of activity provision and poor weather as the main barriers to
      their child's PA. Parental support and child's enjoyment of PA appeared to be
      important facilitators to children participating in PA. CONCLUSION: Improving
      parents' knowledge of the PA recommendations for children, and increasing their
      awareness of the benefits of PA beyond weight status may be an important first
      step for a parenting PA intervention. Although parents commonly perceive
      environmental factors as the main barriers to their child's PA, parental concern
      about low levels of child PA, their capacity to support behaviour change, child
      motivation, self confidence and independence may be key areas to address within
      an intervention to increase child PA. Effective methods of helping parents
      address the latter have been developed in the context of generic parenting
      programmes.

PMID- 23167911
TI  - REsearch into implementation STrategies to support patients of different ORigins
      and language background in a variety of European primary care settings (RESTORE):
      study protocol.
AB  - BACKGROUND: The implementation of guidelines and training initiatives to support
      communication in cross-cultural primary care consultations is ad hoc across a
      range of international settings with negative consequences particularly for
      migrants. This situation reflects a well-documented translational gap between
      evidence and practice and is part of the wider problem of implementing guidelines
      and the broader range of professional educational and quality interventions in
      routine practice. In this paper, we describe our use of a contemporary social
      theory, Normalization Process Theory and participatory research methodology-
      Participatory Learning and Action--to investigate and support implementation of
      such guidelines and training initiatives in routine practice. METHODS: This is a
      qualitative case study, using multiple primary care sites across Europe.
      Purposive and maximum variation sampling approaches will be used to identify and
      recruit stakeholders-migrant service users, general practitioners, primary care
      nurses, practice managers and administrative staff, interpreters, cultural
      mediators, service planners, and policy makers. We are conducting a mapping
      exercise to identify relevant guidelines and training initiatives. We will then
      initiate a PLA-brokered dialogue with stakeholders around Normalization Process
      Theory's four constructs--coherence, cognitive participation, collective action,
      and reflexive monitoring. Through this, we will enable stakeholders in each
      setting to select a single guideline or training initiative for implementation in
      their local setting. We will prospectively investigate and support the
      implementation journeys for the five selected interventions. Data will be
      generated using a Participatory Learning and Action approach to interviews and
      focus groups. Data analysis will follow the principles of thematic analysis, will
      occur in iterative cycles throughout the project and will involve participatory
      co-analysis with key stakeholders to enhance the authenticity and veracity of
      findings. DISCUSSION: This research employs a unique combination of Normalization
      Process Theory and Participatory Learning and Action, which will provide a novel
      approach to the analysis of implementation journeys. The findings will advance
      knowledge in the field of implementation science because we are using and testing
      theoretical and methodological approaches so that we can critically appraise
      their scope to mediate barriers and improve the implementation processes.

PMID- 23167912
TI  - Efficacy of modified minimally invasive surgical technique in the treatment of
      human intrabony defects with or without use of rhPDGF-BB gel: a randomized
      controlled trial.
AB  - AIM: To evaluate the efficacy of modified minimally invasive surgical technique
      (M-MIST) technique with local delivery of recombinant human platelet derived
      growth factor (rhPDGF-BB) gel in the treatment of intrabony defects. MATERIAL AND
      METHODS: Twenty-four healthy subjects were included in the present double
      blinded, randomized, controlled study. Test group was treated with M-MIST and
      rhPDGF-BB and control group with M-MIST alone. RESULTS: The mean probing depth
      (PD), clinical attachment level (CAL) and gingival recession, cementoenamel
      junction to base of the defect (CEJ-BD), defect depth (DD) and cementoenamel
      junction to alveolar crest (CEJ-AC), at baseline to 6 months post-operatively in
      both the groups were statistically significant. Inter-group comparison for gain
      in attachment level (CAL-G), probing depth reduction (PD-R) and change in
      gingival margin position linear bone growth (LBG), percentage bone fill, residual
      defect depth (residual DD) and the change in alveolar crest position revealed no
      statistically significant differences. Gain in CAL and LBG was 3 +/- 0.89 mm and
      1.89 +/- 0.6 in test group and 2.64 +/- 0.67 mm and 1.85 +/- 1.18 mm in control
      group, respectively, and did not show statistical significance. CONCLUSIONS: The
      improvement in both groups could be attributed to the novel surgical technique
      rather than addition of rhPDGF-BB.

PMID- 23167913
TI  - Isolated intestinal transplantation for megacystis microcolon intestinal
      hypoperistalsis syndrome: case report.
AB  - MMIHS is a rare congenital disease. It is characterized by distended urinary
      bladder, small colon and intestinal hypoperistalsis, or aperistalsis with normal
      morphology. There is no specific treatment for MMIHS, and most patients have to
      be maintained by TPN, which frequently causes TPN-related liver failure, loss of
      venous access, or catheter-related sepsis. The prognosis of patients with MMIHS
      is poor, and most patients die early. Multivisceral transplantation including
      stomach, duodenum, intestine, and liver has been used for the treatment of
      patients with MMIHS because these patients often have liver failure. We report an
      eight-yr-old patient with MMIHS who was treated with isolated intestinal
      transplantation. She had completely oral intake during the four yr of follow-up.
      The experience in this case suggests isolated intestinal transplantation may be
      indicated in selected cases with MMIHS.

PMID- 23167914
TI  - Synthesis and characterization of a novel symmetrical sulfone-substituted
      polyphenylene vinylene (SO2EH-PPV) for applications in light emitting devices.
AB  - A novel symmetrical alkylsulfonyl-substituted poly(phenylenevinylene) derivative,
      poly [2,5-bis-(2'-ethylhexylsulfonyl)-1,4-phenylene)vinylene] (SO2EH-PPV), was
      synthesized via palladium-catalyzed Stille coupling, and its electronic and
      optical properties were investigated. The novel PPV derivative was characterized
      by NMR, UV-visible absorption, photoluminescence, gel permeation chromatography,
      infrared spectroscopy, and cyclic voltammetry (CV). The polymer with Mw of 27,800
      and a polydispersity index of 2.6 is readily soluble in common organic solvents,
      such as THF, chloroform, and toluene. The fluorescence quantum yield of the
      polymer, determined against rhodamine 6G in dilute aqueous solutions, was 0.95.
      The HOMO and LUMO levels of SO2EH-PPV were calculated to be -6.0 and -3.61 eV,
      respectively. The results obtained by CV suggest that SO2EH-PPV is a strong
      electron acceptor polymer. Single layer stable polymer light-emitting diode
      devices with the configuration of (ITO/PEDOT:PSS/SO2EH-PPV polymer/Al) were
      fabricated exhibiting a green light emission.

PMID- 23167915
TI  - Iron(III) catalyzed direct synthesis of cis-2,7-disubstituted oxepanes. The
      shortest total synthesis of (+)-isolaurepan.
AB  - Prins cyclization of bis-homoallylic alcohols with aldehydes catalyzed by
      iron(III) salts shows excellent cis selectivity and yields to form 2,7
      disubstituted oxepanes. The iron(III) is able to catalyze this process with
      unactivated olefins. This cyclization was used as the key step in the shortest
      total synthesis of (+)-isolaurepan.

PMID- 23167917
TI  - Bone tissue in different parts of the edentulous maxilla and mandible.
AB  - BACKGROUND: The composition of the fully healed edentulous ridge of the posterior
      maxilla was recently examined and was found to contain about 50% mineralized bone
      and 16% bone marrow. AIM: The objective was to examine the composition of the
      tissue of the fully healed ridge in different portions of the maxilla and the
      mandible in partially dentate subjects. MATERIAL AND METHODS: Eighty-seven
      healthy subjects were included. A trephine drill was used to harvest hard tissue
      specimens. The biopsies were decalcified, embedded in paraffin, sectioned,
      stained, and examined using a point-counting procedure. RESULTS: The marginal
      portion of the jaws almost consistently contained a cortical cap that was
      significantly wider in the mandible than in the maxilla and twice as wide in the
      anterior as in the posterior segments of the mandible. Lamellar bone and bone
      marrow were the dominating tissue elements. Lamellar bone occupied about 63% of
      the tissue in the mandible and 46% in the maxilla. The maxilla contained about
      23% bone marrow as compared to 16% in the mandible. In the mandible, 70%
      (anterior) and 57% (posterior) were made up of lamellar bone. In the maxilla, the
      proportion of lamellar bone in the anterior and posterior segments was similar
      (about 45%). Bone marrow occupied close to 40% of the anterior maxilla, while in
      the posterior maxilla and the anterior and posterior mandible marrow comprised
      between 13 and 18%. CONCLUSION: Marked differences existed with respect to tissue
      composition of the edentulous ridge between the maxilla and the mandible. The
      cortical crest was wider in the mandible than in the maxilla, and widest in the
      symphysis region of the mandible. The proportion of bone marrow was greater in
      the maxilla than in the mandible. The maxillary front tooth region was poor in
      lamellar bone but rich in bone marrow, while the anterior mandible contained
      large amounts of mineralized bone but small amounts of bone marrow.

PMID- 23167916
TI  - Isoflavone retention during processing, bioaccessibility, and transport by Caco-2
      cells: effects of source and amount of fat in a soy soft pretzel.
AB  - The impact of source and amount of lipid used to prepare a soy soft pretzel on
      the bioaccessibility and transport of isoflavones was investigated using the
      coupled in vitro digestion/Caco-2 human cell model. Pretzels were prepared
      without or with 2.9 or 6.0% exogenous lipid from either shortening, canola oil,
      ground almond, or ground hazelnut. The isoflavone backbone structure was stable
      during pretzel production, although there was partial conversion from malonyl and
      acetyl glucosides to simple glucosides and aglycones. Endogenous beta-glucosidase
      activity in ground almond facilitated partial conversion of simple glucosides to
      aglycones during proofing, resulting in a slight decrease in bioaccessibility of
      isoflavones as compared with other sources of lipid. Amount and source of lipid
      did not affect bioaccessibility or uptake and metabolism of isoflavones by Caco-2
      cells, although transport across the monolayer was greater with the lesser amount
      of shortening. These results suggest that the isoflavone structure, but not
      source or amount of lipid in a soy pretzel, may affect bioavailability of
      isoflavones.

PMID- 23167918
TI  - Azaboradibenzo[6]helicene: carrier inversion induced by helical homochirality.
AB  - Azaboradibenzo[6]helicene, a new semiconductor material possessing helical
      chirality, has been synthesized via a tandem bora-Friedel-Crafts-type reaction.
      Unprecedented carrier inversion between the racemate (displaying p-type
      semiconductivity) and the single enantiomer (displaying n-type semiconductivity)
      was observed and can be explained by changes in the molecular packing induced by
      helical homochirality.

PMID- 23167919
TI  - Thrombolysis on ischemic stroke patients with decreased level of consciousness
      within 4.5 h.
AB  - BACKGROUND AND PURPOSE: Few reports concerned on recombinant tissue plasminogen
      activator (rt-PA) treatment in stroke patients with decreased consciousness. This
      study assesses the efficacy and safety of intravenous rt-PA administration within
      4.5 h in stroke patients with decreased consciousness. METHODS: A total of 136
      stroke patients with decreased consciousness, who received or not rt-PA
      intravenously within 4.5 h after stroke onset from Jiangsu province of China from
      2009 to 2012, were reviewed retrospectively. Glasgow Coma Scale (GCS), National
      Institute of Health Stroke Scale (NIHSS), intracranial hemorrhage rate, and
      mortality were used to determine patient outcome when discharged. A 3-month
      outcome was calculated by modified Rankin Scale (mRS) with score 0 to 1
      considered favorable outcome. RESULTS: Baseline characteristics of two groups
      were similar. When discharged, no significant differences were observed regarding
      NIHSS score (P = 0.994) or GCS score (P = 0.591) between groups. After 3 months,
      22.8% patients in rt-PA group had favorable outcome as compared with 7.5%
      patients in control group (P = 0.014). Treatment with rt-PA did not significantly
      increase incidence of hemorrhage (P = 0.494) or mortality (P = 0.169).
      CONCLUSIONS: Intravenous rt-PA administration within 4.5 h after onset of
      symptoms benefited stroke patients with abnormal consciousness.

PMID- 23167920
TI  - Progression of haemophilic arthropathy in children: a Lithuanian--Danish
      comparative study.
AB  - Recurrent bleeding into joints initiates a sequence of events leading to a
      progressive joint damage in people with severe haemophilia. This is a continuous
      process during childhood and adolescence, therefore joint abnormalities may be
      minimal on physical examination in very young children - even those receiving on
      demand treatment. The aim of our study was to quantify the burden of arthropathy
      in Lithuanian patients who had been treated exclusively by on-demand substitution
      and compare their physical joint health with age-matched Danish patients who
      received prophylaxis from an early age. Boys, aged 4-17 years, with severe
      haemophilia and no signs of inhibitors were included in the study. Joint outcome
      based on the Haemophilia Joint Health Score (HJHS) was analysed in two different
      treatment groups and compared within the matched pairs. In total, 32 (16 in each
      treatment group) patients were enroled. A total of 192 joints were evaluated.
      Joint status according to treatment strategy was strikingly different: 27.4 for
      on-demand vs. 3.3 for prophylaxis (<0.001) group. Significance of the difference
      in joint status comparing different treatment strategies was equally strong both
      in younger (4-9 years) and older (10-17 years) patient groups: 2.2 vs. 12.5 (P =
      0.0002) and 3.9 vs. 36.3 (P < 0.0001) respectively. The results further
      demonstrate the unequivocal effect of prophylaxis on joint status and give an
      insight into early and late manifestations of joint impairment based on the HJHS
      in haemophilia patients with treatment on-demand compared with joint changes that
      may develop over the time with the preventative treatment.

PMID- 23167922
TI  - Characterization of 2,4-dichlorophenoxyacetic acid and 2,4,5
      trichlorophenoxyacetic acid-degrading fungi in Vietnamese soils.
AB  - Sixty-nine fungal strains were isolated countrywide from 10 Vietnamese soils, in
      areas both with and without a history of exposure to Agent Orange, and their
      degrading activities on the phenoxy acid herbicides 2,4-dichlorophenoxyacetic
      acid (2,4-D) and 2,4,5-trichlorophenoxyacetic acid (2,4,5-T), as well as related
      compounds, were examined. Among taxonomically various fungi, 45, 12 and 4% of the
      isolates degraded phenoxyacetic acid (PA), 2,4-D and 2,4,5-T, respectively. While
      the PA-degrading fungi were distributed to all sites and among many genera, the
      2,4-D-degraders were found only in order Eurotiales in class Eurotiomycetes. All
      of the 2,4,5-T-degrading fungal strains were phylogenetically close to
      Eupenicillium spp. and were isolated from southern Vietnam. As a degradation
      intermediate, the corresponding phenol compounds were detected in some strains.
      The degradation substrate spectrum for 26 compounds of Eupenicillium spp. strains
      including 2,4,5-T-degraders and -non-degraders seemed to be related to
      phylogenetic similarity and soil sampling location of the isolates. These results
      suggest that the heavily contaminated environments enhanced the adaptation of the
      phylogenetic group of Eupenicillium spp. toward to obtain the ability to degrade
      2,4,5-T.

PMID- 23167921
TI  - Polycystic kidneys have decreased vascular density: a micro-CT study.
AB  - OBJECTIVE: Polycystic kidney disease (PKD) is a common cause of end-stage renal
      failure and many of these patients suffer vascular dysfunction and hypertension.
      It remains unclear whether PKD is associated with abnormal microvascular
      structure. Thus, this study examined the renovascular structure in PKD. METHODS:
      PKD rats (PCK model) and controls were studied at 10 weeks of age, and mean
      arterial pressure (MAP), renal blood flow, and creatinine clearance were
      measured. Microvascular architecture and cyst number and volume were assessed
      using micro-computed tomography, and angiogenic pathways evaluated. RESULTS:
      Compared with controls, PKD animals had an increase in MAP (126.4 +/- 4.0 vs.
      126.2 +/- 2.7 mmHg) and decreased clearance of creatinine (0.39 +/- 0.09 vs. 0.30
      +/- 0.05 mL/min), associated with a decrease in microvascular density, both in
      the cortex (256 +/- 22 vs. 136 +/- 20 vessels per cm2) and medullar (114 +/- 14
      vs. 50 +/- 9 vessels/cm2) and an increase in the average diameter of glomeruli
      (104.14 +/- 2.94 vs. 125.76 +/- 9.06 mm). PKD animals had increased fibrosis (2.2
      +/- 0.2 fold vs. control) and a decrease in the cortical expression in hypoxia
      inducible factor 1-alpha and vascular endothelial growth factor. CONCLUSIONS: PKD
      animals have impaired renal vascular architecture, which can have significant
      functional consequences. The PKD microvasculature could represent a therapeutic
      target to decrease the impact of this disease.

PMID- 23167923
TI  - The continuing question of how fever duration is associated with patient outcome.
AB  - Although fever magnitude and etiology have been associated with outcomes of
      critically ill patients, possible associations between fever duration and
      mortality remain inconclusive. Since long-lasting fever is generally attributed
      to severe pathologic conditions, it is expected to be an indicator of adverse
      outcome. It also seems plausible that persistent fever in specific patient
      groups, mainly those with cerebral damage or limited cardiorespiratory reserve,
      could lead to worsened outcomes. Existing studies on these associations have been
      considerably limited because of methodological flaws, which may account for
      controversial findings that have been reported. Well-designed, large-sample
      studies using diverse measures of fever duration need to be conducted. 

PMID- 23167924
TI  - Efficient catalyst-free four-component synthesis of novel gamma-aminoethers
      mediated by a Mannich type reaction.
AB  - Herein, it is provided an efficient and one-pot procedure for the synthesis of
      novel and diversely substituted gamma-aminoethers in good yields through a four
      component process by treatment of benzylamines with polyformaldehyde and
      activated alkenes in aliphatic alcohols acting both as solvent and as
      etherificant agents. Reactions proceeded via a Mannich-type reaction, where the
      formation of iminium ions and aminals was identified as the key intermediates to
      obtain the target products. 

PMID- 23167926
TI  - Response to John; use of HbA1c in the diagnosis of diabetes mellitus in the UK.

PMID- 23167927
TI  - A survey of spinal collateral actions of feline ventral spinocerebellar tract
      neurons.
AB  - The aim of this study was to identify spinal target cells of spinocerebellar
      neurons, in particular the ventral spinocerebellar tract (VSCT) neurons, giving
      off axon collaterals terminating within the lumbosacral enlargement. Axons of
      spinocerebellar neurons were stimulated within the cerebellum while searching for
      most direct synaptic actions on intracellularly recorded hindlimb motoneurons and
      interneurons. In motoneurons the dominating effects were inhibitory [inhibitory
      postsynaptic potentials (IPSPs) in 67% and excitatory postsynaptic potentials
      (EPSPs) in 17% of motoneurons]. Latencies of most IPSPs indicated that they were
      evoked disynaptically and mutual facilitation between these IPSPs and disynaptic
      IPSPs evoked by group Ia afferents from antagonist muscles and group Ib and II
      afferents from synergists indicated that they were relayed by premotor
      interneurons in reflex pathways from muscle afferents. Monosynaptic EPSPs from
      the cerebellum were accordingly found in Ia inhibitory interneurons and
      intermediate zone interneurons with input from group I and II afferents but only
      oligosynaptic EPSPs in motoneurons. Monosynaptic EPSPs following cerebellar
      stimulation were also found in some VSCT neurons, indicating coupling between
      various spinocerebellar neurons. The results are in keeping with the previously
      demonstrated projections of VSCT neurons to the contralateral ventral horn,
      showing that VSCT neurons might contribute to motor control at a spinal level.
      They might thus play a role in modulating spinal activity in advance of any
      control exerted via the cerebellar loop.

PMID- 23167929
TI  - Relationship between fumonisin production and FUM gene expression in Fusarium
      verticillioides under different environmental conditions.
AB  - Fusarium verticillioides is the main source of fumonisins, a group of mycotoxins
      that can contaminate maize-based food and feed and cause diseases in humans and
      animals. The study of the effect of different environmental conditions on toxin
      production should provide information that can be used to develop strategies to
      minimize the risk. This study analysed the effect of temperature (15 degrees C-35
      degrees C), water activity (a(w): 0.999-0.93), salinity (0-125 g l(-1) NaCl) and
      pH (5-8) on the growth and production of fumonisins B(1) (FB1), B(2) (FB2) and
      B(3) (FB3) and the expression of FUM1 and FUM21 in F. verticillioides. The
      highest growth rate was measured at 25 degrees C, a(w) of 0.998-0.99 and 0-25 g
      l(-1) of NaCl. Optimal conditions for fumonisin production were 30 degrees C,
      a(w) of 0.99, 25 g l(-1) of NaCl and pH 5; nevertheless, the strain showed a good
      adaptability and was able to produce moderate levels of fumonisins under a wide
      range of conditions. Gene expression mirrored fumonisin production profile under
      all conditions with the exception of temperature: FUM1 and FUM21 expression was
      highest at 15 degrees C, while maximum fumonisin production was at 30 degrees C.
      These data indicate that a post-transcriptional regulation mechanism could
      account for the different optimal temperatures for FUM gene expression and
      fumonisin production.

PMID- 23167930
TI  - MicroRNA expression profile associated with response to neoadjuvant
      chemoradiotherapy in locally advanced rectal cancer patients.
AB  - BACKGROUND: Rectal cancer accounts for approximately one third of all colorectal
      cancers (CRC), which belong among leading causes of cancer deaths worldwide.
      Standard treatment for locally advanced rectal cancer (cT3/4 and/or cN+) includes
      neoadjuvant chemoradiotherapy with fluoropyrimidines (capecitabine or 5
      fluorouracil) followed by radical surgical resection. Unfortunately, a
      significant proportion of tumors do not respond enough to the neoadjuvant
      treatment and these patients are at risk of relapse. MicroRNAs (miRNAs) are small
      non-coding RNAs playing significant roles in the pathogenesis of many cancers
      including rectal cancer. MiRNAs could present the new predictive biomarkers for
      rectal cancer patients. METHODS: We selected 20 patients who underwent
      neoadjuvant chemoradiotherapy for advanced rectal cancer and whose tumors were
      classified as most sensitive or resistant to the treatment. These two groups were
      compared using large-scale miRNA expression profiling. RESULTS: Expression levels
      of 8 miRNAs significantly differed between two groups. MiR-215, miR-190b and miR
      29b-2* have been overexpressed in non-responders, and let-7e, miR-196b, miR-450a,
      miR-450b-5p and miR-99a* have shown higher expression levels in responders. Using
      these miRNAs 9 of 10 responders and 9 of 10 non-responders (p < 0.05) have been
      correctly classified. CONCLUSIONS: Our pilot study suggests that miRNAs are part
      of the mechanisms that are involved in response of rectal cancer to the
      chemoradiotherapy and that miRNAs may be promising predictive biomarkers for such
      patients. In most miRNAs we identified (miR-215, miR-99a*, miR-196b, miR-450b-5p
      and let-7e), the connection between their expression and radioresistance or
      chemoresistance to inhibitors of thymidylate synthetase was already established.

PMID- 23167925
TI  - Ethosuximide, valproic acid, and lamotrigine in childhood absence epilepsy:
      initial monotherapy outcomes at 12 months.
AB  - PURPOSE: Determine the optimal initial monotherapy for children with newly
      diagnosed childhood absence epilepsy (CAE) based on 12 months of double-blind
      therapy. METHODS: A double-blind, randomized controlled clinical trial compared
      the efficacy, tolerability, and neuropsychological effects of ethosuximide,
      valproic acid, and lamotrigine in children with newly diagnosed CAE. Study
      medications were titrated to clinical response, and subjects remained in the
      trial unless they reached a treatment failure criterion. Maximal target doses
      were ethosuximide 60 mg/kg/day or 2,000 mg/day, valproic acid 60 mg/kg/day or
      3,000 mg/day, and lamotrigine 12 mg/kg/day or 600 mg/day. Original primary
      outcome was at 16-20 weeks and included a video-electroencephalography (EEG)
      assessment. For this report, the main effectiveness outcome was the freedom from
      failure rate 12 months after randomization and included a video-EEG assessment;
      differential drug effects were determined by pairwise comparisons. The main
      cognitive outcome was the percentage of subjects experiencing attentional
      dysfunction at the month 12 visit. KEY FINDINGS: A total of 453 children were
      enrolled and randomized; 7 were deemed ineligible and 446 subjects comprised the
      overall efficacy cohort. There were no demographic differences between the three
      cohorts. By 12 months after starting therapy, only 37% of all enrolled subjects
      were free from treatment failure on their first medication. At the month 12
      visit, the freedom-from-failure rates for ethosuximide and valproic acid were
      similar (45% and 44%, respectively; odds ratio [OR]with valproic acid vs.
      ethosuximide 0.94; 95% confidence interval [CI] 0.58-1.52; p = 0.82) and were
      higher than the rate for lamotrigine (21%; OR with ethosuximide vs. lamotrigine
      3.08; 95% CI 1.81-5.33; OR with valproic acid vs. lamotrigine 2.88; 95% CI 1.68
      5.02; p < 0.001 for both comparisons). The frequency of treatment failures due to
      lack of seizure control (p < 0.001) and intolerable adverse events (p < 0.037)
      was significantly different among the treatment groups. Almost two thirds of the
      125 subjects with treatment failure due to lack of seizure control were in the
      lamotrigine cohort. The largest subgroup (42%) of the 115 subjects discontinuing
      due to adverse events was in the valproic acid group. The previously reported
      higher rate of attentional dysfunction seen at 16-20 weeks in the valproic acid
      group compared with the ethosuximide or lamotrigine groups persisted at 12 months
      (p < 0.01). SIGNIFICANCE: As initial monotherapy, the superior effectiveness of
      ethosuximide and valproic acid compared to lamotrigine in controlling seizures
      without intolerable adverse events noted at 16-20 weeks persisted at 12 months.
      The valproic acid cohort experienced a higher rate of adverse events leading to
      drug discontinuation as well as significant negative effects on attentional
      measures that were not seen in the ethosuximide cohort. These 12-month outcome
      data coupled with the study's prespecified decision-making algorithm indicate
      that ethosuximide is the optimal initial empirical monotherapy for CAE. This is
      the first randomized controlled trial meeting International League Against
      Epilepsy (ILAE) criteria for class I evidence for CAE (or for any type of
      generalized seizure in adults or children). (NCT00088452.).

PMID- 23167931
TI  - Association between single nucleotide polymorphism of PD-L1 gene and non-small
      cell lung cancer susceptibility in a Chinese population.
AB  - AIM: To evaluate the correlation between a polymorphism of PD-L1 gene and the
      susceptibility of non-small cell lung cancer (NSCLC) in a Chinese population.
      METHODS: A total of 293 Chinese patients with NSCLC and 293 age and sex matched
      controls of the same ethnic origin were enrolled in this study. A/C polymorphism
      at position 8923 in intron 4 of PD-L1 gene was typed using the polymerase chain
      reaction-restriction fragment length polymorphism method (PCR-RFLP). The
      interactions between A/C genotype, allele frequency and NSCLC susceptibility were
      analyzed. RESULTS: The A/C genotype frequencies were significantly different
      between NSCLC patients and controls. The AC and CC frequencies were higher in
      NSCLC patients than in controls (16.4 vs 8.9%, 1.0 vs 0.3%, respectively). The C
      allele frequency was higher in NSCLC patients than in controls (9.2 vs 4.8%).
      Significant differences in the A and C allele frequencies were noted between the
      two groups (chi(2) = 8.864, P = 0.003). More risk of NSCLC was found in
      individuals carrying the C allele than in those carrying the A allele (OR =
      2.203; 95% CI 1.262-3.242). In both light smokers (<=20 pack-years) and heavy
      smokers (>20 pack-years), individuals carrying the C-allele had more risk of
      NSCLC than those carrying the A-allele (light smokers OR = 1.847, 95% CI 1.001
      3.409; heavy smokers OR = 3.252, 95% CI 1.196-8.845, respectively). CONCLUSION:
      An A/C polymorphism at position 8923 in the PD-L1 gene is associated with NSCLC
      susceptibility. The PD-L1 polymorphism plays a role in NSCLC, especially in
      patients with the C-allele.

PMID- 23167932
TI  - Glycogen synthase kinase-3 levels and phosphorylation undergo large fluctuations
      in mouse brain during development.
AB  - OBJECTIVES: Dysregulated glycogen synthase kinase-3 (GSK3) may contribute to the
      pathophysiology of mood disorders and other diseases, and appears to be a target
      of certain therapeutic drugs. The growing recognition of heightened vulnerability
      during development to many psychiatric diseases, including mood disorders, led us
      to test if there are developmental changes in mouse brain GSK3 and its regulation
      by phosphorylation and by therapeutic drugs. METHODS: GSK3 levels and
      phosphorylation were measured at seven ages of development in the mouse cerebral
      cortex and hippocampus. RESULTS: Two periods of rapid transitions in GSK3 levels
      were identified: a large rise between postnatal days 1 and 2 and three weeks of
      age, where GSK3 levels were as much as fourfold higher than adult mouse brain
      levels, and a rapid decline between 2-4 and eight weeks of age, when adult levels
      were reached. Inhibitory serine-phosphorylation of GSK3, particularly GSK3beta,
      was extremely high in the one-day postnatal mouse brain, and rapidly declined
      thereafter. These developmental changes in GSK3 were equivalent in the male and
      female cerebral cortex, and differed from other signaling kinases, including Akt,
      extracellular-regulated kinases 1/2, c-Jun N-terminal kinase, and p38 levels and
      phosphorylation. In contrast to the adult mouse brain, where administration of
      lithium or fluoxetine rapidly and robustly increased serine-phosphorylation of
      GSK3, in young mice these responses were blunted or absent. CONCLUSIONS: High
      brain levels of GSK3 and large fluctuations in its levels and phosphorylation in
      the juvenile and adolescent mouse brain raise the possibility that they may
      contribute to destabilized mood regulation induced by environmental and genetic
      factors.

PMID- 23167933
TI  - Differential relations between fronto-limbic metabolism and executive function in
      patients with remitted bipolar I and bipolar II disorder.
AB  - OBJECTIVES: The aim of this study was to investigate the relationship between
      resting brain glucose metabolism and cognitive profiles in patients with remitted
      bipolar I disorder (BD-I) and bipolar II disorder (BD-II). We hypothesized that
      BD-I patients (compared to BD-II patients) would perform worse on tests of
      cognitive function because of abnormal metabolism in the prefrontal cortex and
      other mood-related brain areas. METHODS: Thirty-four patients with remitted
      bipolar disorder (BD) (BD-I = 17, BD-II = 17) under treatment and 17 well-matched
      healthy controls received both fluorodeoxyglucose ((18) F-FDG) positron emission
      tomography (PET) and neuropsychological tests of attention, memory, and executive
      function. RESULTS: Clinical features in patients with BD-I and BD-II were
      comparable. Executive function, as indicated by performance on the Wisconsin Card
      Sorting Test, was significantly worse (i.e., higher percentage of errors, lower
      percentage of conceptual level responses, and fewer categories completed) in BD-I
      patients than in BD-II patients and healthy subjects. No difference in attention
      and memory tests was found among these three groups. Brain PET analysis showed
      that BD-I patients (compared to BD-II patients) had significantly lower glucose
      uptake in the bilateral anterior cingulum, insula, striatum, and part of the
      prefrontal cortex, and higher glucose uptake in the left parahippocampus. Further
      analyses revealed significant correlations between poor executive function and
      abnormal glucose uptake in other brain areas in BD-I patients. CONCLUSIONS: There
      are neurobiological differences between subtypes of BD. BD-I is associated with
      more impaired fronto-limbic circuitry, which might account for reduced executive
      function in BD-I patients during remission.

PMID- 23167934
TI  - ADHD comorbidity can matter when assessing cortical thickness abnormalities in
      patients with bipolar disorder.
AB  - OBJECTIVES: Attention-deficit hyperactivity disorder (ADHD) is prevalent in
      patients with bipolar disorder (BP), but very few studies consider this when
      interpreting magnetic resonance imaging findings. No studies, to our knowledge,
      have screened for or controlled for the presence of ADHD when examining cortical
      thickness in patients with BP. We used a 2 * 2 design to evaluate the joint
      effects of BP and ADHD on cortical thickness and uncover the importance of ADHD
      comorbidity in BP subjects. METHODS: The study included 85 subjects: 31 healthy
      controls, 17 BP-only, 19 ADHD-only, and 18 BP/ADHD. All patients with BP were
      subtype I, euthymic, and not taking lithium. Groups did not differ significantly
      in age or gender distribution. We used cortical thickness measuring tools
      combined with cortical pattern matching methods to align sulcal/gyral anatomy
      across participants. Significance maps were used to check for both main effects
      of BP and ADHD and their interaction. Post-hoc comparisons assessed how the
      effects of BP on cortical thickness varied as a function of the presence or
      absence of ADHD. RESULTS: Interactions of BP and ADHD diagnoses were found in the
      left subgenual cingulate and right orbitofrontal cortex, demonstrating that the
      effect of BP on cortical thickness depends on ADHD status. CONCLUSIONS: Some
      brain abnormalities attributed to BP may result from the presence of ADHD.
      Diagnostic interactions were found in regions previously implicated in the
      pathophysiology of BP, making it vital to control for an ADHD comorbid diagnosis
      when attempting to isolate neural or genetic abnormalities specific to BP.

PMID- 23167935
TI  - Evaluating sleep in bipolar disorder: comparison between actigraphy,
      polysomnography, and sleep diary.
AB  - OBJECTIVES: Bipolar disorder is an illness characterized by sleep and circadian
      disturbance, and monitoring sleep in this population may signal an impending mood
      change. Actigraphy is an important clinical and research tool for examining
      sleep, but has not yet been systematically compared to polysomnography or sleep
      diary in bipolar disorder. The present study compares actigraphy,
      polysomnography, and sleep diary estimates of five standard sleep parameters in
      individuals with bipolar disorder and matched controls across two nights of
      assessment. METHODS: Twenty-seven individuals who met diagnostic criteria for
      bipolar disorder type I or II and were currently between mood episodes, along
      with 27 matched controls with no history of psychopathology or sleep disturbance,
      underwent two nights of research laboratory monitoring. Sleep was estimated via
      polysomnography, actigraphy, and sleep diary. RESULTS: Over the 108 nights
      available for comparison, sleep parameter estimates from actigraphy and
      polysomnography were highly correlated and did not differ between the two groups
      or across the two nights for sleep onset latency, wake after sleep onset, number
      of awakenings, total sleep time, or sleep efficiency percentage. The medium wake
      threshold algorithm in the actigraphy software was the most concordant with
      polysomnography and diaries across the five sleep parameters. Concordance between
      actigraphy, polysomnography, and sleep diary was largely independent of insomnia
      presence and medication use. CONCLUSIONS: Actigraphy is a valid tool for
      estimating sleep length and fragmentation in bipolar disorder.

PMID- 23167936
TI  - Total white matter hyperintensity volume in bipolar disorder patients and their
      healthy relatives.
AB  - OBJECTIVES: White matter hyperintensities (WMH) are more common in subjects with
      bipolar disorder (BP) than in healthy subjects (HS). Few studies have examined
      the effect of the diagnostic type of bipolar illness on WMH burden, and none have
      approached this question through a direct measurement of the volume of affected
      white matter in relationship to familiality. In this pilot study, we utilized a
      volumetric measurement of WMH to investigate the relationship between the total
      volume of WMH and the familiality and type of BP. METHODS: Forty-five individuals
      with bipolar I disorder (BP-I) with psychotic features, BP-I without psychotic
      features, or bipolar II disorder (BP-II), seven of their unaffected relatives,
      and 32 HS were recruited for participation. T-2 weighted magnetic resonance
      imaging scans were obtained on all subjects, and the total volume of all WMH for
      each subject was measured in cubic centimeters. The significance of difference
      between groups was tested using ANOVA with post-hoc adjustment for multiple
      comparisons. Further, we used logistic regression to test for trends between
      symptom load and total WMH volume. RESULTS: The mean total volume of WMH in BP-I
      patients with psychotic features was significantly higher (p < 0.05) than that of
      HS. Further, we observed a positive linear trend by familiality and type of
      affectedness when comparing mean total WMH volume of HS, unaffected family
      members, subjects with BP-II, and BP-I with and without a history of psychosis (p
      < 0.05). CONCLUSIONS: Based on a quantitative technique, WMH burden appears to be
      associated with familiality and type of BP. The significance of these findings
      remains to be fully elucidated.

PMID- 23167938
TI  - A new case of keratoconus associated with Williams-Beuren syndrome.
AB  - BACKGROUND: Williams-Beuren syndrome is a multisystemic genetic disorder caused
      by a contiguous gene deletion at 7q11.23. Keratoconus is a complex disease and it
      is suspected to have a genetic origin, although the specific gene responsible for
      keratoconus has not been identified. Although there are several ocular features
      in Williams-Beuren syndrome, keratoconus is not regularly described as part of
      this syndrome. PURPOSE: To report a new patient with keratoconus and Williams
      Beuren syndrome. DISCUSSION: This is the third case of an association between
      Williams-Beuren syndrome and keratoconus. The authors believe that the Williams
      Beuren syndrome chromosome region can be a possible target for further
      investigation as the genetic basis of keratoconus.

PMID- 23167939
TI  - Pornography actresses: an assessment of the damaged goods hypothesis.
AB  - The damaged goods hypothesis posits that female performers in the adult
      entertainment industry have higher rates of childhood sexual abuse (CSA),
      psychological problems, and drug use compared to the typical woman. The present
      study compared the self-reports of 177 porn actresses to a sample of women
      matched on age, ethnicity, and marital status. Comparisons were conducted on
      sexual behaviors and attitudes, self-esteem, quality of life, and drug use. Porn
      actresses were more likely to identify as bisexual, first had sex at an earlier
      age, had more sexual partners, were more concerned about contracting a sexually
      transmitted disease (STD), and enjoyed sex more than the matched sample, although
      there were no differences in incidence of CSA. In terms of psychological
      characteristics, porn actresses had higher levels of self-esteem, positive
      feelings, social support, sexual satisfaction, and spirituality compared to the
      matched group. Last, female performers were more likely to have ever used 10
      different types of drugs compared to the comparison group. A discriminant
      function analysis was able to correctly classify 83% of the participants
      concerning whether they were a porn actress or member of the matched sample.
      These findings did not provide support for the damaged goods hypothesis. 

PMID- 23167940
TI  - Suture restriction of the temporal bone as a risk factor for acute otitis media
      in children: cohort study.
AB  - BACKGROUND: Eustachian tube (ET) dysfunction plays an important role in the
      pathogenesis of acute otitis media (AOM). Unfortunately, there is a lack of
      knowledge about the exact role of the ET's bony support, the temporal bone, on
      occurrence of AOM. This study investigates whether severe suture restriction of
      the temporal bone is a risk factor for development of AOM in young children.
      METHODS: Using a prospective cohort design, 64 children aged 6 to 18 months
      without prior history of AOM were followed during the cold season (September 2009
      to April 2010). Temporal bone status (categorized as with or without severe
      suture restriction) was evaluated using palpation and a cranial bone mobility
      test. Information about potential baseline confounders and risk factors for AOM
      (gender, age, birth weight, gestational age, use of pacifier, daycare attendance,
      presence of siblings, low socioeconomic status, breastfeeding >= 6 months,
      parental smoking and history of upper respiratory tract infection) were also
      collected. Occurrence of AOM diagnosed by physicians blinded to temporal bone
      status was the main outcome. Data were analyzed using hierarchical linear and
      nonlinear (multilevel) models. RESULTS: Severe suture restriction of the temporal
      bone was identified in 23 children (35.9%). At least one AOM episode was
      diagnosed in 14 (48.3%) of the ears associated with temporal bones previously
      identified as having severe suture restriction and in 28 (28.3%) of those without
      severe suture restriction. Higher risk for AOM was explained by severe suture
      restriction of the temporal bone (adjusted relative risk (RR), 2.26, 95% CI 1.43
      to 2.91, p<.01), pacifier use (RR, 2.59, 95% CI 1.51 to 3.22, p<.01) and younger
      age (RR, 0.22, 95% CI 0.10 to 0.52, p=.001). CONCLUSIONS: The study results
      indicate that severe suture restriction of the temporal bone is a risk factor for
      AOM in young children. Subsequent intervention studies are needed to determine if
      this mechanical risk factor can be modified in young children.

PMID- 23167941
TI  - Antimicrobial susceptibility of Aeromonas spp. isolated from pig ileum segments
      to natural isothiocyanates.
AB  - With this study we intend to evaluate the effects of 8 different glucosinolate
      hydrolysis products including isothiocyanates as antibacterial compounds against
      Aeromonadaceae, isolated from intestinal segments of pigs collected directly from
      slaughter-houses in the North of Portugal. Four Aeromonas species, A.
      allosaccharophila, A. hydrophila, A. media and A. veronii were identified. Using
      disc-diffusion bioassay all compounds were tested at 6 different doses (0.015,
      0.15, 0.75, 1.5 and 3.0 umoles) in dimethyl-sulfoxide (DMSO). Antibiotic standard
      (gentamicin) and DMSO (negative control) were included in all experiments.
      Minimum and maximum dose inhibitions (in umoles) were assessed. To our knowledge,
      this is the first study of antimicrobial activity of glucosinolate hydrolysis
      products against Aeromonas species. The results showed that glucosinolate
      hydrolysis products and particularly the isothiocyanates have antimicrobial
      activity, which was proportional to the concentration used. However, not all
      revealed the same tendency, which means that the chemical structure of each
      compound is fundamental to understand their effectiveness. Among the different
      isothiocyanates the benzylisothiocyanate, sulforaphane and 2
      phenylethylisothiocyanate were the most effective in vitro inhibitors of
      bacterial growth. This in vitro study provides enough data to demonstrate the
      potential use of these natural dietary chemicals for treating infectious diseases
      caused by Aeromonas spp. 

PMID- 23167942
TI  - Novel structurally varied N-alkyl 1,4-dihydropyridines as ABCB1 inhibitors:
      structure-activity relationships, biological activity and first bioanalytical
      evaluation.
AB  - Series of structurally varied N-alkyl 1,4-dihydropyridines and novel benzo
      annelated derivatives as 1,4- dihydroquinolines have been characterized as ABCB1
      inhibitors. Structure-activity relationships (SARs) are discussed. Cytotoxic
      activities of selected compounds have been determined. A first bioanalysis of
      ABCB1 substrate properties has been carried out in a cell-based model. Compounds
      with highest ABCB1 inhibiting activities were no substrates of ABCB1 and not
      transported by the efflux pump, thus profiling the new ABCB1 inhibitors.

PMID- 23167943
TI  - Novel solid-phase parallel synthesis of N-substituted-2-aminobenzo [d]thiazole
      derivatives via cyclization reactions of 2-iodophenyl thiourea intermediate
      resin.
AB  - A novel solid-phase methodology has been developed for the synthesis of N-alkyl,
      N-acyl, and N-sulfonyl-2-aminobenzo[d]thiazole derivatives. The key step in this
      procedure involves the preparation of polymer-bound 2-aminobenzo[d]thiazole
      resins 5 by cyclization reaction of 2-iodophenyl thiourea resin 3. The resin
      bound 2-iodophenyl thiourea 3 is produced by addition of 2-iodophenyl
      isothiocyanate 2 to the amine-terminated linker amide resin 1. These core
      skeleton 2-aminobenzo[d]thiazole resins 5 undergo functionalization reactions
      with various electrophiles, such as alkyl halides, acid chlorides, and sulfonyl
      chlorides to generate N-alkyl, N-acyl, and N-sulfonyl-2-aminobenzo[d]thiazole
      resins 6, 7, and 8, respectively. Finally, N-alkyl, N-acyl, and N-sulfonyl-2
      aminobenzo[d]thiazole derivatives 9, 10, and 11 are then generated in good yields
      and purities by cleavage of the respective resins 6, 7, and 8 using
      trifluoroacetic acid (TFA) in dichloromethane (DCM). 

PMID- 23167944
TI  - Accessory mental foramina: prevalence, position and diameter assessed by cone
      beam computed tomography and digital panoramic radiographs.
AB  - OBJECTIVE: To investigate the presentation of accessory mental foramina (AMF) on
      cone-beam computed tomography (CBCT) and digital panoramic examinations (PAN).
      STUDY DESIGN: Imaging examinations (i.e., CBCT and PAN) of 100 patients (200 hemi
      mandibles) were assessed. AMF prevalence, diameter, and location related to
      adjacent teeth and to the mental foramen (MF) were analyzed. RESULTS: On CBCT
      images, the AMF was observed in 3% of the patients: two unilateral cases and one
      bilateral case, with mean diameter of 0.93 mm (+/-0.3); no AMF was identified on
      PAN. Most AMF were located between the premolars, either superiorly (two cases)
      or mesially (two cases) to the MF. The mean horizontal distance to the
      corresponding MF was 2.3 mm (+/-1.0) and the mean vertical distance was 4.0 mm
      (+/-0.7). CONCLUSIONS: The results of this study suggest that CBCT is an
      effective tool for presurgical tridimensional assessment of the neurovascular
      structures, such as MF and its variations; On the other hand, PAN examinations
      were not able to show the AMF cases assessed on CBCT.

PMID- 23167946
TI  - Dynamics of uranyl peroxide nanocapsules.
AB  - Discrete aqueous metal oxide polyionic clusters that include aluminum
      polycations, transition-metal polyoxometalates, and the actinyl peroxide clusters
      have captivated the interest of scientists in the realm of both their fundamental
      and applied chemistries. Yet the counterions for these polycations or polyanions
      are often ignored, even though they are imperative for solubility,
      crystallization, purification, and even templating cluster formation. The actinyl
      peroxide clusters have counterions not only external, but internal to the hollow
      peroxide capsules. In this study, we reveal the dynamic behavior of these
      internal alkali counterions via solid-state and liquid NMR experiments. These
      studies on two select cluster geometries, those containing 24 and 28 uranyl
      polyhedra, respectively, show that the capsules-like clusters are not rigid
      entities. Rather, the internal alkalis both have mobility inside the capsules, as
      well as exchange with species in the media in which they are dissolved. The
      alkali mobilities are affected by both what is inside the clusters as well as the
      composition of the dissolving medium.

PMID- 23167945
TI  - Non-invasive mechanical ventilation in hematology patients: let's agree on
      several things first.
AB  - Acute respiratory failure is a dreaded and life-threatening event that represents
      the main reason for ICU admission. Respiratory events occur in up to 50% of
      hematology patients, including one-half of those admitted to the ICU. Mortality
      from acute respiratory failure in hematology patients depends on the patient's
      general status, acute respiratory failure etiology, need for mechanical
      ventilation and associated organ dysfunction. Non-invasive mechanical ventilation
      is clearly beneficial for chronic obstructive pulmonary disease exacerbation and
      cardiogenic pulmonary edema. These benefits are based mainly on the avoidance of
      invasive mechanical ventilation complications. Non-invasive mechanical has also
      been recommended in hematology patients with acute respiratory failure but its
      real benefits remain unclear in these settings. There is growing concern about
      the safety of non-invasive mechanical ventilation to treat hypoxemic acute
      respiratory failure overall, but also in hematology patients. Prophylactic non
      invasive mechanical ventilation in patients with acute respiratory failure but
      not respiratory distress seems to be effective in hematology patients with a
      reduced rate of intubation. However, curative non-invasive mechanical ventilation
      should be restricted to those patients with isolated respiratory failure, with
      fast improvement of respiratory distress under non-invasive mechanical
      ventilation, and with rapid switch to intubation to avoid deleterious delays in
      optimal invasive mechanical ventilation. 

PMID- 23167947
TI  - Glycosidic bond cleavage in deoxynucleotides: effects of solvent and the DNA
      phosphate backbone in the computational model.
AB  - Density functional theory (B3LYP) was employed to examine the hydrolysis of the
      canonical 2'-deoxynucleotides in varied environments (gas phase or water) using
      different computational models for the sugar residue (methyl or phosphate group
      at C5') and nucleophile (water activated through full or partial proton
      abstraction). Regardless of the degree of nucleophile activation, our results
      show that key geometrical parameters along the reaction pathway are notably
      altered upon direct inclusion of solvent effects in the optimization routine,
      which leads to significant changes in the reaction energetics and better
      agreement with experiment. Therefore, despite the wide use of gas-phase
      calculations in the literature, small model computational work, as well as large
      scale enzyme models, that strive to understand nucleotide deglycosylation must
      adequately describe the environment. Alternatively, although inclusion of the
      phosphate group at C5' also affects the geometries of important stationary
      points, the effects cancel to yield unchanged deglycosylation barriers, and
      therefore smaller computational models can be used to estimate the energy
      associated with nucleotide deglycosylation, with the 5' phosphate group included
      if full (geometric) details of the reaction are desired. Hydrogen-bonding
      interactions with the nucleobase can significantly reduce the barrier to
      deglycosylation, which supports suggestions that discrete hydrogen-bonding
      interactions with active-site amino acid residues can play a significant role in
      enzyme-catalyzed nucleobase excision. Taken together with previous studies, the
      present work provides vital clues about the components that must be included in
      future studies of the deglycosylation of isolated noncanonical nucleotides, as
      well as the corresponding enzyme-catalyzed reactions.

PMID- 23167949
TI  - Synthesis, isolation, structure elucidation, and color properties of 10-acetyl
      pyranoanthocyanins.
AB  - Grape anthocyanins reacted with diacetyl, a secondary metabolite of
      microorganisms involved in winemaking, to form 10-acetyl-pyranoanthocyanins, a
      type of anthocyanin-derived pigment similar to other vitisin-type
      pyranoanthocyanins found in red wines. The structures of 10-acetyl-pyranomalvidin
      3-beta-O-glucoside and 10-acetyl-pyranopeonidin-3-beta-O-glucoside were confirmed
      by spectroscopic methods (UV-vis, MS/MS, and NMR) after their synthesis and
      isolation. In contrast to other vitisin-type pyranoanthocyanins, the newly
      described 10-acetyl-pyranoanthocyanins exhibited differentiated color-related
      properties. They showed an important tendency to occur as colorless hemiacetals
      at C-10 under wine pH conditions, while co-occurrence of flavylium cation and
      quinoidal base yielded a broad visible absorbance band around 510-520 nm.
      Moreover, they easily reacted with bisulfite in acidic aqueous solution (pH 2.0),
      but the expected bleaching was not observed. Bisulfite bonded to the carbonyl of
      10-acetyl substituent instead of the expected C-10 position of the
      pyranoanthocyanin core, thus giving rise to a red pigment hypsochromically
      shifted toward orangish nuances (maximum absorbances at 487-491 nm).

PMID- 23167950
TI  - Uterine leiomyosarcoma presenting as breast metastasis.

PMID- 23167951
TI  - Gene tree correction for reconciliation and species tree inference.
AB  - BACKGROUND: Reconciliation is the commonly used method for inferring the
      evolutionary scenario for a gene family. It consists in "embedding" inferred gene
      trees into a known species tree, revealing the evolution of the gene family by
      duplications and losses. When a species tree is not known, a natural algorithmic
      problem is to infer a species tree from a set of gene trees, such that the
      corresponding reconciliation minimizes the number of duplications and/or losses.
      The main drawback of reconciliation is that the inferred evolutionary scenario is
      strongly dependent on the considered gene trees, as few misplaced leaves may lead
      to a completely different history, with significantly more duplications and
      losses. RESULTS: In this paper, we take advantage of certain gene trees'
      properties in order to preprocess them for reconciliation or species tree
      inference. We flag certain duplication vertices of a gene tree, the "non-apparent
      duplication" (NAD) vertices, as resulting from the misplacement of leaves. In the
      case of species tree inference, we develop a polynomial-time heuristic for
      removing the minimum number of species leading to a set of gene trees that
      exhibit no NAD vertices with respect to at least one species tree. In the case of
      reconciliation, we consider the optimization problem of removing the minimum
      number of leaves or species leading to a tree without any NAD vertex. We develop
      a polynomial-time algorithm that is exact for two special classes of gene trees,
      and show a good performance on simulated data sets in the general case.

PMID- 23167952
TI  - Negative axillary ultrasonography with biopsy may predict non-involvement of the
      non-sentinel lymph nodes in operable breast cancer patients.
AB  - AIM: To evaluate whether axillary ultrasound in combination with a biopsy (AUS +/
      Bx) can predict the involvement of the non-sentinel lymph nodes (NSLN). METHODS:
      A review of all operable breast cancer patients who underwent AUS +/- Bx at our
      tertiary care center from January 2010 to April 2011 was performed. All patients
      underwent AUS as part of their pre-operative evaluation. If the AUS was
      suspicious, a fine-needle aspiration or core-needle biopsy was performed.
      RESULTS: Of 88 patients included in our final analysis, 20 (23%) had positive AUS
      + Bx and underwent axillary lymph node dissection (ALND) at time of definitive
      surgery. In all, 68 of the 88 patients (77.3%) had negative AUS +/- Bx and
      underwent sentinel lymph node (SLN) Bx at the time of definitive surgery. If the
      SLN Bx was negative, no further axillary surgery was performed and the NSLN were
      assumed to be negative. If the SLN Bx was positive, ALND was performed. Of the 68
      patients, 62 (91%) had a negative NSLN. Patients with positive AUS + Bx carry a
      relative risk of 2.02 (P < 0.00002) of having positive NSLN. CONCLUSION: In
      operable breast cancer patients, a negative AUS+/- Bx may be a predictor of non
      involvement of the NSLN.

PMID- 23167948
TI  - National, regional, and global trends in adult overweight and obesity
      prevalences.
AB  - BACKGROUND: Overweight and obesity prevalence are commonly used for public and
      policy communication of the extent of the obesity epidemic, yet comparable
      estimates of trends in overweight and obesity prevalence by country are not
      available. METHODS: We estimated trends between 1980 and 2008 in overweight and
      obesity prevalence and their uncertainty for adults 20 years of age and older in
      199 countries and territories. Data were from a previous study, which used a
      Bayesian hierarchical model to estimate mean body mass index (BMI) based on
      published and unpublished health examination surveys and epidemiologic studies.
      Here, we used the estimated mean BMIs in a regression model to predict overweight
      and obesity prevalence by age, country, year, and sex. The uncertainty of the
      estimates included both those of the Bayesian hierarchical model and the
      uncertainty due to cross-walking from mean BMI to overweight and obesity
      prevalence. RESULTS: The global age-standardized prevalence of obesity nearly
      doubled from 6.4% (95% uncertainty interval 5.7-7.2%) in 1980 to 12.0% (11.5
      12.5%) in 2008. Half of this rise occurred in the 20 years between 1980 and 2000,
      and half occurred in the 8 years between 2000 and 2008. The age-standardized
      prevalence of overweight increased from 24.6% (22.7-26.7%) to 34.4% (33.2-35.5%)
      during the same 28-year period. In 2008, female obesity prevalence ranged from
      1.4% (0.7-2.2%) in Bangladesh and 1.5% (0.9-2.4%) in Madagascar to 70.4% (61.9
      78.9%) in Tonga and 74.8% (66.7-82.1%) in Nauru. Male obesity was below 1% in
      Bangladesh, Democratic Republic of the Congo, and Ethiopia, and was highest in
      Cook Islands (60.1%, 52.6-67.6%) and Nauru (67.9%, 60.5-75.0%). CONCLUSIONS:
      Globally, the prevalence of overweight and obesity has increased since 1980, and
      the increase has accelerated. Although obesity increased in most countries,
      levels and trends varied substantially. These data on trends in overweight and
      obesity may be used to set targets for obesity prevalence as requested at the
      United Nations high-level meeting on Prevention and Control of NCDs.

PMID- 23167953
TI  - Vitamin C supplementation in relation to inflammation in individuals with
      atrophic gastritis: a randomised controlled trial in Japan.
AB  - Evidence has shown that both C-reactive protein (CRP) and serum amyloid component
      A (SAA) are increased in individuals with gastritis and stomach cancer.
      Controlling the level of these biomarkers by inhibiting the gastric infection
      with high doses of ascorbic acid may reduce the risk of carcinogenesis. A
      population-based double-blind randomised controlled trial in a Japanese
      population with atrophic gastritis in an area of high stomach cancer incidence
      was conducted between 1995 and 2000. Daily doses of 50 or 500 mg vitamin C were
      given, and 120 and 124 participants completed the 5-year study, respectively.
      Although serum ascorbic acid was higher in the high-dosage group (1.73 (SD 0.46)
      MUg/l) than in the low-dosage group (1.49 (SD 0.29) MUg/l, P< 0.001), at the end
      of the study, no significant difference was observed for CRP between the low- and
      high-dosage groups (0.39 (95 % CI 0.04, 4.19) mg/l and 0.38 (95 % CI 0.03, 4.31)
      mg/l, respectively; P= 0.63) or for SAA between the low- and high-dosage groups
      (3.94 (95 % CI 1.04, 14.84) MUg/ml and 3.85 (95 % CI 0.99, 14.92) MUg/ml,
      respectively; P= 0.61). Vitamin C supplementation may not have a strong effect on
      reducing infections in individuals with atrophic gastritis.

PMID- 23167954
TI  - An oxidopyrylium cyclization/ring-opening route to polysubstituted alpha
      hydroxytropolones.
AB  - alpha-Hydroxytropolones are a class of molecules with therapeutic potential
      against several human diseases. However, structure-activity relationship studies
      on these molecules have been limited due to a scarcity of efficient synthetic
      methods to access them. It is demonstrated herein that alpha-hydroxytropolones
      can be generated through a BCl(3)-mediated ring
      opening/aromatization/demethylation process on 8-oxabicyclo[3.2.1]octenes. Used
      in conjunction with an improved method based on established oxidopyrylium dipolar
      cycloadditions, several polysubstituted alpha-hydroxytropolones can be accessed
      in three steps from readily available alpha-hydroxy-gamma-pyrones.

PMID- 23167955
TI  - Small-scale oxygen distribution determines the vinyl chloride biodegradation
      pathway in surficial sediments of riverbed hyporheic zones.
AB  - Surficial riverbed sediments are often characterized by sharp redox gradients
      between the aerobic benthic sediment and underlying anoxic sediment, potentially
      representing an ideal niche for aerobic and anaerobic vinyl chloride (VC)
      degraders. To test this, the fate of VC in aerobic and anaerobic microcosms
      containing surficial sediment of a riverbed hyporheic zone receiving VC
      contaminated groundwater was explored. Quantitative PCR showed that
      Dehalococcoides 16S rRNA gene and VC reductive dehalogenase-encoding genes (vcrA,
      bvcA) were highly enriched in anaerobic microcosms, with stoichiometric
      conversion of VC to ethene. In aerobic microcosms, etnC and etnE involved in
      aerobic ethene/VC oxidation were enriched with concomitant low or no accumulation
      of ethene. However, Dehalococcoides 16S rRNA gene, vcrA and bvcA copy numbers
      were also enriched in oxygen-exposed microcosms containing sediment with high
      organic carbon and small grain size, whereas they were reduced in oxygen-exposed
      sediment with low organic carbon and larger grain size in line with extensive
      oxygen penetration into the sediment. These results suggest the coexistence and
      coactivity of anaerobic and aerobic VC degraders in the same small volume of
      surficial sediment and that oxygen distribution, as determined by sediment grain
      size and organic matter content, affects the local VC-degrading bacterial
      community and VC biodegradation pathway.

PMID- 23167956
TI  - Visual mismatch negativity is sensitive to symmetry as a perceptual category.
AB  - We investigated the sensitivity of visual mismatch negativity (vMMN) to an
      abstract and non-semantic category, vertical mirror symmetry. Event-related
      potentials (ERPs) elicited by random and symmetric square patterns, delivered in
      passive oddball paradigm (participants played a video game), were recorded. In
      one of the conditions, symmetric patterns were frequent (standard) stimuli and
      the random patterns were infrequent (deviant) stimuli; in the other condition,
      the probabilities were reversed. We compared the ERPs elicited by symmetric
      stimuli as deviants and as standards, and, similarly, the ERPs elicited by the
      random deviants and random standards. As the difference between the ERPs elicited
      by random deviant and random standard stimuli, a posterior negativity emerged in
      two latency ranges (112-120 and 284-292 ms). These negativities were considered
      to be vMMN components. We suggest that the two vMMN components are organised in
      cascade error signals. However, there was no significant difference between the
      ERPs elicited by symmetric deviants and those elicited by symmetric standards.
      The emergence of vMMN in response to the deviant random stimuli is considered to
      be a deviation of a perceptual category (in the symmetric standard sequence
      presented). Accordingly, random stimuli acquired no perceptual category; for this
      reason, the symmetric deviant (in the random standard sequence presented)
      elicited no vMMN. The results show that the memory system underlying vMMN is
      capable of coding perceptual categories such as bilateral symmetry, even if the
      stimulus patterns are unrelated to the ongoing behavior.

PMID- 23167957
TI  - Why rodent pseudogenes refuse to retire.
AB  - A new study in this issue of Genome Biology sheds light on why some pseudogenes
      persist in rodent, and other mammalian, genomes. 

PMID- 23167958
TI  - Transient lack of glucose but not O2 is involved in ischemic postconditioning
      induced neuroprotection.
AB  - AIM: Cerebral ischemic postconditioning has emerged recently as a kind of
      endogenous strategy for neuroprotection. We set out to test whether hypoxia or
      glucose deprivation (GD) would substitute for ischemia in postconditioning.
      METHODS: Adult male C57BL/6J mice were treated with postconditioning evoked by
      ischemia (bilateral common carotid arteries occlusion) or hypoxia (8% O(2) )
      after 45-min middle cerebral arterial occlusion. Corticostriatal slices from mice
      were subjected to 1-min oxygen-glucose deprivation (OGD), GD, or oxygen
      deprivation (OD) postconditioning at 5 min after 15-min OGD. RESULTS: Hypoxic
      postconditioning did not decrease infarct volume or improve neurologic function
      at 24 h after reperfusion, while ischemic postconditioning did. Similarly, OGD
      and GD but not OD postconditioning attenuated the OGD/reperfusion-induced injury
      in corticostriatal slices. The effective duration of low-glucose (1 mmol/L)
      postconditioning was longer than that of OGD postconditioning. Moreover, OGD and
      GD but not OD postconditioning reversed the changes of glutamate, GABA, glutamate
      transporter-1 protein expression, and glutamine synthetase activity induced by
      OGD/reperfusion. CONCLUSIONS: These results suggest that the transient lack of
      glucose but not oxygen plays a key role in ischemic postconditioning-induced
      neuroprotection, at least partly by regulating glutamate metabolism. Low-glucose
      postconditioning might be a clinically safe and feasible therapeutic approach
      against cerebral ischemia/reperfusion injury.

PMID- 23167959
TI  - Functional status after lung transplantation in older adults in the post
      allocation score era.
AB  - This manuscript describes the functional status trajectory of older (age 65 or
      older) and younger (age 18-64) adults after lung transplantation (LT). After the
      implementation of the lung allocation score (LAS) in 2005, older adults became
      the fastest growing subgroup of recipients. Yet the impact of LT on physical
      function, a main determinant of quality of life in older adults, is unknown. We
      conducted a retrospective cohort study using United Network for Organ Sharing
      data on 4805 adults who received a LT during 2005-2009. We divided them into
      older (>=65; n = 774) and younger (18-64; n = 4031) cohorts. Functional status
      was measured by Karnofsky performance score (KPS). Mixed models estimated the
      impact of age group on the rate of functional decline starting at 1 year
      posttransplantation. We controlled for KPS at transplantation, gender, race,
      diagnosis, LAS and LT type. Age group was not associated with different rates of
      decline in KPS over time. On average, recipients who were older, received a
      single LT, or had a low KPS at transplantation had worse functional status
      posttransplantation when compared to their counterparts, but rarely reached
      disability at 48 months. Overall, LT had a positive and durable effect on
      physical function for both older and younger recipients.

PMID- 23167960
TI  - Relationship between endoscopic and histologic gastric atrophy and intestinal
      metaplasia.
AB  - BACKGROUND: The severity of endoscopic gastric atrophy (EGA), high-stage
      Operative Link on Gastritis Assessment (OLGA) gastritis (i.e., stage III or IV),
      and extensive intestinal metaplasia (IM) with incomplete subtype have been
      separately reported as high-risk factors of gastric cancer (GC). The aim of this
      study was to evaluate the associations between these endoscopic and pathologic
      characteristics. MATERIALS AND METHODS: A cross-sectional study was conducted on
      280 patients with functional dyspepsia at the University Medical Center at Ho Chi
      Minh City, Vietnam. Biopsies were taken according to the updated Sydney System.
      EGA was assessed according to the Kimura-Takemoto classification, and gastritis
      stage was assessed according to the OLGA system. RESULTS: All of patients with
      high-stage OLGA gastritis (i.e., stage III or IV) clustered in the subgroup of
      patients with moderate-to-severe EGA: 13/126 (10.3%) in patients with moderate-to
      severe EGA versus 0/154 (0%) in patients with none-to-mild EGA (p < .001).
      Moderate-to-severe EGA was also significantly associated with extensive IM (p <
      .001, OR = 28.1 (CI 95% 6.4-173.3)) and incomplete IM subtype (p < .001, OR =
      36.7 (CI 95% 5.1-742.1). Extensive IM was also associated with incomplete IM
      subtype (p = .01). CONCLUSIONS: High-stage OLGA gastritis, extensive IM with
      incomplete subtype clustered in patients with moderate-to-severe EGA. Assessing
      the severity of EGA could potentially help to identify patients who should be
      taken systemic biopsy for evaluating GC risk.

PMID- 23167961
TI  - Intratracheal transplantation of human umbilical cord blood-derived mesenchymal
      stem cells dose-dependently attenuates hyperoxia-induced lung injury in neonatal
      rats.
AB  - Intratracheal transplantation of human umbilical cord blood (UCB)-derived
      mesenchymal stem cells (MSCs) attenuates the hyperoxia-induced neonatal lung
      injury. The aim of this preclinical translation study was to optimize the dose of
      human UCB-derived MSCs in attenuating hyperoxia-induced  lung injury in newborn
      rats. Newborn Sprague-Dawley rats were randomly exposed to hyperoxia (95% oxygen)
      or normoxia after birth for 14 days. Three different doses of human UCB-derived
      MSCs, 5 * 10(3) (HT1), 5 * 10(4) (HT2), and 5 * 10(5) (HT3),  were delivered
      intratracheally at postnatal day (P) 5. At P14, lungs were harvested for analyses
      including morphometry for alveolarization, terminal deoxynucleotidyl transferase
      mediated deoxyuridine triphosphate nick end labeling (TUNEL) staining,
      myeoloperoxidase activity, mRNA level of  tumor necross factor-alpha (TNF-alpha),
      interleukin-1beta (IL-1beta), IL-6, and transforming growth factor-beta (TGF
      beta), human glyceradehyde-3-phosphate dehydrogenase (GAPDH), and p47(phox), and
      collagen levels. Increases in TUNEL-positive cells were attenuated  in all
      transplantation groups. However, hyperoxia-induced lung injuries, such as reduced
      alveolarization, as evidenced by increased mean linear intercept and mean
      alveolar volume, and increased collagen levels were significantly attenuated in
      both HT2 and HT3, but not in HT1, with better attenuation  in HT3 than in HT2.
      Dose-dependent human GAPDH expression, indicative of the presence of human RNA in
      lung tissue, was observed only in the transplantation groups, with higher
      expression in HT3 than in HT2, and higher expression in HT2 than in HT1.
      Hyperoxia-induced inflammatory responses  such as increased myeloperoxidase
      acitivity, mRNA levels of TNF-alpha, IL-1beta, IL-6, and TGF-beta of the lung
      tissue, and upregulation of both cytosolic and membrane p47(phox), indicative of
      oxidative stress, were significantly attenuated in both HT2 and HT3 but not  in
      HT1. These results demonstrate that intratracheal transplantation of human UCB
      derived MSCs with appropriate doses may attenuate hyperoxia-induced lung injury
      through active involvement of these cells in modulating host inflammatory
      responses and oxidative stress in neonatal rats.

PMID- 23167963
TI  - The HOPS proteins hVps41 and hVps39 are required for homotypic and heterotypic
      late endosome fusion.
AB  - The homotypic fusion and protein sorting (HOPS) complex is a multisubunit
      tethering complex that in yeast regulates membrane fusion events with the
      vacuole, the yeast lysosome. Mammalian homologs of all HOPS components have been
      found, but little is known about their function. Here, we studied the role of
      hVps41 and hVps39, two components of the putative human HOPS complex, in the endo
      lysosomal pathway of human cells. By expressing hemagglutinin (HA)-tagged
      constructs, we show by immunoelectron microscopy (immunoEM) that both hVps41 and
      hVps39 associate with the limiting membrane of late endosomes as well as
      lysosomes. Small interference RNA (siRNA)-mediated knockdown of hVps41 or hVps39
      resulted in an accumulation of late endosomes, a depletion in the number of
      lysosomes and a block in the degradation of endocytosed cargo. Lysosomal pH and
      cathepsin B activity remained unaltered in these conditions. By immunoEM we found
      that hVps41 or hVps39 knockdown impairs homotypic fusion between late endosomes
      as well as heterotypic fusion between late endosomes and lysosomes. Thus, our
      data show that both hVps41 and hVps39 are required for late endosomal-lysosomal
      fusion events and the delivery of endocytic cargo to lysosomes in human cells.

PMID- 23167964
TI  - Dilute nitride and GaAs n-i-p-i solar cells.
AB  - We demonstrate for the first time the operation of GaInNAs and GaAs n-i-p-i
      doping solar cells with ion-implanted selective contacts. Multiple layers of
      alternate doping are grown by molecular beam epitaxy to form the n-i-p-i
      structure. After growth, vertical selective contacts are fabricated by Mg and Si
      ion implantation, followed by rapid thermal annealing treatment and fabrication
      into circular mesa cells. As means of characterisation, spectral response and
      illuminated current-voltage (I-V) were measured on the samples. The spectral
      response suggests that all horizontal layers are able to contribute to the
      photocurrent. Performance of the devices is discussed with interest in the n-i-p
      i structure as a possible design for the GaInP/GaAs/GaInNAs tandem solar cell.

PMID- 23167965
TI  - Theoretical prediction of the complexation behaviors of antitumor platinum drugs
      with cucurbiturils.
AB  - The inclusion complex formation ability between CB[n] (n = 6-9) and Pt-drugs
      (oxaliplatin, nedaplatin, carboplatin, and cisplatin) in gas phase as well as
      water phases has been investigated using the using density functional theory. The
      results reveal the existence of several stable inclusion complexes in aqueous
      solution with high solvation energies compared to the guest and host molecule. It
      has been shown that the formation of complexes between CB[6] and Pt-drugs
      resulted in structural change in the CB[6], with the calculated deformation
      energies being higher for the inclusion complexes. The inclusion complexes are
      stabilized by the hydrogen bonding and the charge transfer between the Pt-drugs
      and the CB[n] host. Calculated enthalpy and Gibbs free energy of formation in
      aqueous solution revels that the formation of CB[7]-oxaliplatin is spontaneous,
      and hence its experimental synthesis is feasible. Among the CB's studied, CB[8]
      Pt-drug inclusion complexes have exothermic enthalpy and low Gibbs free energy of
      formation. Computed (1)NMR spectra in CB[7]-oxaliplatin showed high chemical
      shielding for the cyclohexane ring, indicating the existence of charge transfer
      in the inclusion complex. The amine protons in the guest Pt-drugs are shielded
      due to the hydrogen bonding interaction with CB's oxygen portal.

PMID- 23167966
TI  - How I do it--sole innominate cannulation for acute type A aortic dissection.
AB  - We describe sole direct innominate cannulation for arterial return for
      establishing both cardiopulmonary bypass and selective antegrade cerebral
      perfusion in the repair of acute type A dissection and compare it with femoral,
      axillary, direct aortic and apical cannulations. We believe innominate
      cannulation has all the advantages of right axillary cannulation and none of its
      disadvantages. It can be used in all patients in whom innominate artery is not
      dissected, obstructed, calcified or otherwise diseased.

PMID- 23167967
TI  - Dendritic cell subsets in mycobacterial infection: control of bacterial growth
      and T cell responses.
AB  - Anti-mycobacterial immunity is guided by specialised antigen presenting cells
      known as dendritic cells, which are essential for both initiating and maintaining
      T cell immune responses during infection. The dendritic cell population can be
      divided into functionally distinct subsets that differ in their ability to
      present antigen and produce key TH1 cytokines, such as IL-12. This review
      discusses recent studies, in murine models, investigating which dendritic cell
      populations are important for mycobacterial control.

PMID- 23167968
TI  - Reversible brain response to an intragastric load of L-lysine under L-lysine
      depletion in conscious rats.
AB  - L-Lysine (Lys) is an essential amino acid and plays an important role in
      anxiogenic behaviour in both human subjects and rodents. Previous studies have
      shown the existence of neural plasticity between the Lys-deficient state and the
      normal state. Lys deficiency causes an increase in noradrenaline release from the
      hypothalamus and serotonin release from the amygdala in rats. However, no studies
      have used functional MRI (fMRI) to compare the brain response to ingested Lys in
      normal, Lys-deficient and Lys-recovered states. Therefore, in the present study,
      using acclimation training, we performed fMRI on conscious rats to investigate
      the brain response to an intragastric load of Lys. The brain responses to
      intragastric administration of Lys (3 mmol/kg body weight) were investigated in
      six rats intermittently in three states: normal, Lys-deficient and recovered
      state. First, in the normal state, an intragastric load of Lys activated several
      brain regions, including the raphe pallidus nucleus, prelimbic cortex and the
      ventral/lateral orbital cortex. Then, after 6 d of Lys deprivation from the
      normal state, an intragastric load of Lys activated the ventral tegmental area,
      raphe pallidus nucleus and hippocampus, as well as several hypothalamic areas.
      After recovering from the Lys-deficient state, brain activation was similar to
      that in the normal state. These results indicate that neural plasticity in the
      prefrontal cortex, hypothalamic area and limbic system is related to the internal
      Lys state and that this plasticity could have important roles in the control of
      Lys intake.

PMID- 23167969
TI  - Set size, individuation, and attention to shape.
AB  - Much research has demonstrated a shape bias in categorizing and naming solid
      objects. This research has shown that when an entity is conceptualized as an
      individual object, adults and children attend to the object's shape. Separate
      research in the domain of numerical cognition suggest that there are distinct
      processes for quantifying small and large sets of discrete items. This research
      shows that small set discrimination, comparison, and apprehension is often
      precise for 1-3 and sometimes 4 items; however, large numerosity representation
      is imprecise. Results from three experiments suggest a link between the processes
      for small and large number representation and the shape bias in a forced choice
      categorization task using naming and non-naming procedures. Experiment 1 showed
      that adults generalized a newly learned name for an object to new instances of
      the same shape only when those instances were presented in sets of less than 3 or
      4. Experiment 2 showed that preschool children who were monolingual speakers of
      three different languages were also influenced by set size when categorizing
      objects in sets. Experiment 3 extended these results and showed the same effect
      in a non-naming task and when the novel noun was presented in a count-noun syntax
      frame. The results are discussed in terms of a relation between the precision of
      object representation and the precision of small and large number representation.

PMID- 23167970
TI  - Cleaved cytokeratin-18 is a mechanistically informative biomarker in idiopathic
      pulmonary fibrosis.
AB  - BACKGROUND: Stress of the endoplasmic reticulum (ER) leading to activation of the
      unfolded protein response (UPR) and alveolar epithelial cell (AEC) apoptosis may
      play a role in the pathogenesis of idiopathic pulmonary fibrosis (IPF). Our
      objectives were to determine whether circulating caspase-cleaved cytokeratin-18
      (cCK-18) is a marker of AEC apoptosis in IPF, define the relationship of cCK-18
      with activation of the UPR, and assess its utility as a diagnostic biomarker.
      METHODS: IPF and normal lung tissues were stained with the antibody (M30) that
      specifically binds cCK-18. The relationship between markers of the UPR and cCK-18
      was determined in AECs exposed in vitro to thapsigargin to induce ER stress. cCK
      18 was measured in serum from subjects with IPF, hypersensitivity pneumonitis
      (HP), nonspecific interstitial pneumonia (NSIP), and control subjects. RESULTS:
      cCK-18 immunoreactivity was present in AECs of IPF lung, but not in control
      subjects. Markers of the UPR (phosphorylated IRE-1alpha and spliced XBP-1) were
      more highly expressed in IPF type II AECs than in normal type II AECs.
      Phosphorylated IRE-1alpha and cCK-18 increased following thapsigargin-induced ER
      stress. Serum cCK-18 level distinguished IPF from diseased and control subjects.
      Serum cCK-18 was not associated with disease severity or outcome. CONCLUSIONS:
      cCK-18 may be a marker of AEC apoptosis and UPR activation in patients with IPF.
      Circulating levels of cCK-18 are increased in patients with IPF and cCK-18 may be
      a useful diagnostic biomarker.

PMID- 23167971
TI  - Inferior early posttransplant outcomes for recipients of right versus left
      deceased donor kidneys: an ANZDATA registry analysis.
AB  - Anatomical differences between right and left kidneys could influence transplant
      outcome. We compared graft function and survival for left and right kidney
      recipients transplanted from the same deceased organ donor. Adult recipients of
      4900 single kidneys procured from 2450 heart beating deceased donors in Australia
      and New Zealand from 1995 to 2009 were included in a paired analysis. Right
      kidneys were associated with more delayed graft function (DGF) (25 vs. 21% for
      left kidneys, p < 0.001) and, if not affected by DGF, a slower fall in serum
      creatinine. One-year graft survival was lower for right kidneys (89.1 vs. 91.1%
      for left kidneys, p = 0.001), primarily attributed to surgical complications (66
      versus 35 failures for left kidneys). Beyond the first posttransplant year,
      kidney side was not associated with eGFR, graft or patient survival. Receipt of a
      right kidney is a risk factor for inferior outcomes in the first year after
      transplantation. A higher incidence of surgical complications suggests the
      shorter right renal vein may be contributory. The higher susceptibility of right
      kidneys to injury should be considered in organ allocation.

PMID- 23167972
TI  - Impact of evergreening on patients and health insurance: a meta analysis and
      reimbursement cost analysis of citalopram/escitalopram antidepressants.
AB  - BACKGROUND: "Evergreening" refers to the numerous strategies whereby owners of
      pharmaceutical products use patent laws and minor drug modifications to extend
      their monopoly privileges on the drug. We aimed to evaluate the impact of
      evergreening through the case study of the antidepressant citalopram and its
      chiral switch form escitalopram by evaluating treatment efficacy and
      acceptability for patients, as well as health insurance costs for society.
      METHODS: To assess efficacy and acceptability, we performed meta-analyses for
      efficacy and acceptability. We compared direct evidence (meta-analysis of results
      of head-to-head trials) and indirect evidence (adjusted indirect comparison of
      results of placebo-controlled trials). To assess health insurance costs, we
      analyzed individual reimbursement data from a representative sample of the French
      National Health Insurance Inter-regime Information System (SNIIR-AM) from 2003 to
      2010, which allowed for projecting these results to the whole SNIIR-AM population
      (53 million people). RESULTS: In the meta-analysis of seven head-to-head trials
      (2,174 patients), efficacy was significantly better for escitalopram than
      citalopram (combined odds ratio (OR) 1.60 (95% confidence interval 1.05 to
      2.46)). However, for the adjusted indirect comparison of 10 citalopram and 12
      escitalopram placebo-controlled trials, 2,984 and 3,777 patients respectively,
      efficacy was similar for the two drug forms (combined indirect OR 1.03 (0.82 to
      1.30)). Because of the discrepancy, we could not combine direct and indirect data
      (test of inconsistency, P = 0.07). A similar discrepancy was found for treatment
      acceptability. The overall reimbursement cost burden for the citalopram,
      escitalopram and its generic forms was 120.6 million Euros in 2010, with 96.8
      million Euros for escitalopram. CONCLUSIONS: The clinical benefit of escitalopram
      versus citalopram remains uncertain. In our case of evergreening, escitalopram
      represented a substantially high proportion of the overall reimbursement cost
      burden as compared with citalopram and the generic forms.

PMID- 23167973
TI  - Adaptor protein complexes AP-4 and AP-5: new players in endosomal trafficking and
      progressive spastic paraplegia.
AB  - The adaptor proteins (APs) are a family of five heterotetrameric complexes with
      important functions in vesicle trafficking. While the roles of APs 1-3 are
      broadly established, comparatively little is known about AP-4 and AP-5. Current
      evidence suggests that AP-4 mediates TGN to endosome transport of specific cargo
      proteins, such as the amyloid precursor protein APP, and that it is involved in
      basolateral sorting in polarized cells. Furthermore, several independent studies
      have reported human patients with mutations in AP-4 genes. AP-4 deficiency causes
      severe intellectual disability and progressive spastic para- or tetraplegia,
      supporting an important role for AP-4 in brain function and development. The
      newly discovered AP-5 complex appears to be involved in endosomal dynamics; its
      precise localization and function are still unclear. Intriguingly, AP-5
      deficiency is also associated with progressive spastic paraplegia, suggesting
      that AP-5, like AP-4, plays a fundamental role in neuronal development and
      homeostasis. The unexpected phenotypic parallels between AP-4 and AP-5 patients
      may in turn suggest a functional relationship of the two APs in vesicle
      trafficking.

PMID- 23167974
TI  - Comparative validity of depression assessment scales for screening poststroke
      depression.
AB  - INTRODUCTION: This study aimed to compare screening properties of four assessment
      scales for poststroke depression (PSD) at 2 weeks and 1 year after index stroke,
      and investigated factors contributing to misclassification. METHODS: A total of
      423 patients were evaluated 2 weeks after stroke and 288 (68%) were followed 1
      year later, and were diagnosed as having major and minor PSD applying DSM-IV
      criteria gold standards. The Beck Depression Inventory (BDI), Hospital Anxiety
      and Depression Scale-depression subscale (HADS-D), Hamilton Rating Scale for
      Depression (HAMD), and Montgomery-Asberg Depression Rating Scale (MADRS) were
      administered. The balance of sensitivity and specificity was assessed using
      receiver operating characteristics (ROC) analysis. RESULTS: Discriminating
      abilities of all the scales for major and all PSD were good (area under ROC
      values 0.88-0.93 and 0.88-0.92 at 2 weeks; and 0.93-0.96 and 0.89-0.91 at 1 year,
      respectively). Misclassification was influenced by demographic characteristics
      and stroke severity particularly for the BDI and HAMD, was more marked for all
      PSD than for major PSD, and was more prominent at 2 weeks than at 1 year after
      stroke. LIMITATIONS: Patients with only mild to moderate stroke severity were
      included. CONCLUSIONS: Although there were no marked differences in the screening
      abilities for PSD between the scales, differences were found in factors
      influencing misclassification. Assessment scales with less somatic items may be
      recommended for the screening of PSD, particularly at the acute phase of stroke.

PMID- 23167975
TI  - Treatment preferences in patients with first episode depression.
AB  - BACKGROUND: Treatment preferences of patients suffering from depression may
      affect adherence and clinical outcomes. This study examines associations between
      patients' treatment preferences, their characteristics and illness
      representations of depression. METHODS: Illness representations of depression
      (IPQ-R), treatment acceptability and preferences were assessed in 88 newly
      diagnosed patients with first episode depression. Other measures recorded:
      gender, age, education level, income, psychiatric comorbidity, depressive
      symptomatology (PHQ-9), a family history of depression, and current treatment of
      depression. Multiple logistic regression was used to identify factors associated
      with a preference for psychotherapy. RESULTS: Psychotherapy was preferred by 41%
      of participants, while 31% favored antidepressants. Acceptability was strongly
      associated with preference. Patients preferring psychotherapy perceived that
      their depression has more serious consequences than those preferring medication
      and were more likely to attribute their depression to social causes than
      psychological or physical causes. Participants who preferred psychotherapy were
      more likely to be female, have a university degree and have a family history of
      depression. LIMITATIONS: The cross-sectional design precludes causal
      interpretations. CONCLUSIONS: Preferences vary according to gender, level of
      education, family history and illness representations. It may be important to
      provide accurate information on both treatments and discuss patients' preferences
      before prescribing treatment.

PMID- 23167976
TI  - Complementary roles of medial temporal lobes and mid-dorsolateral prefrontal
      cortex for working memory for novel and familiar trial-unique visual stimuli.
AB  - It has been suggested that working memory (WM) for novel information requires the
      medial temporal lobes (MTL), but is not necessary for WM for familiar stimuli. In
      previous studies that directly compared WM for novel and familiar stimuli, only
      the novel stimuli were trial-unique. Here, 16 young human subjects performed a
      Sternberg WM task with visual scenes while in a functional magnetic resonance
      imaging scanner. All task stimuli were trial-unique, but were either new (Novel
      condition) or previously learned (Familiar condition). This design allowed
      investigation of whether MTL and prefrontal cortex (PFC) activity is related
      specifically to the novelty/familiarity of the stimuli or to their trial-unique
      status during WM. We observed greater hippocampal and parahippocampal activity
      during encoding and maintenance for novel than for familiar stimuli. In contrast,
      right mid-dorsolateral PFC (dlPFC) activity was greater during encoding of
      familiar than novel stimuli. The mid-dlPFC was not recruited during maintenance
      or for retrieval when the Familiar condition was contrasted with the Novel
      condition. However, left mid-dlPFC activity was present at retrieval when correct
      Match trials (i.e. hits) were contrasted with correct Non-match trials (i.e.
      correct rejections) for the Novel condition. The results support the hypothesis
      that MTL regions are required for the encoding and maintenance of novel stimuli
      during WM, demonstrating that the observed MTL activity is not related to the
      trial-uniqueness of the stimuli per se. Furthermore, the observed activation
      pattern in mid-dlPFC suggests a role for the mid-dlPFC in executive control
      associated processes related to monitoring of scene familiarity at encoding and
      retrieval during WM.

PMID- 23167978
TI  - Glycaemic index and glycaemic load in relation to risk of diabetes-related
      cancers: a meta-analysis.
AB  - Diets high in glycaemic index (GI) or glycaemic load (GL) have been hypothesised
      to increase the risks of certain cancers by increasing blood glucose or insulin
      concentrations. We aimed to conduct a meta-analysis of prospective cohort studies
      to evaluate the association between GI or GL and diabetes-related cancers (DRC),
      including bladder, breast, colon-rectum, endometrium, liver and pancreas, which
      are associated with an increased risk for diabetes, and prostate cancer, which is
      associated with a reduced risk for diabetes. We searched Pubmed, EMBASE and
      MEDLINE databases up to September 2011 and reference lists of relevant articles.
      Relative risks (RR) and 95 % CI for the highest v. the lowest categories were
      extracted and pooled using a random-effects model. Thirty-six prospective cohort
      studies with a total of 60 811 DRC cases were included in the present meta
      analysis. In a comparison of the highest and lowest categories, the pooled RR of
      DRC were 1.07 (95 % CI 1.04, 1.11; n 30) for GI and 1.02 (95 % CI 0.96, 1.08; n
      33) for GL. In an analysis of site-specific cancer risks, we found significant
      associations for GI in relation to breast cancer (RR 1.06; 95 % CI 1.02, 1.11; n
      11) and colorectal cancer (RR 1.08; 95 % CI 1.00, 1.17; n 9 studies). GL was
      significantly associated with the risk of endometrial cancer (RR 1.21; 95 % CI
      1.07, 1.37; n 5). In conclusion, the findings of the present study suggest a
      modest-to-weak association between a diet that induces a high glucose response
      and DRC risks.

PMID- 23167977
TI  - Schwann cell myelination requires Dynein function.
AB  - BACKGROUND: Interaction of Schwann cells with axons triggers signal transduction
      that drives expression of Pou3f1 and Egr2 transcription factors, which in turn
      promote myelination. Signal transduction appears to be mediated, at least in
      part, by cyclic adenosine monophosphate (cAMP) because elevation of cAMP levels
      can stimulate myelination in the absence of axon contact. The mechanisms by which
      the myelinating signal is conveyed remain unclear. RESULTS: By analyzing
      mutations that disrupt myelination in zebrafish, we learned that Dynein
      cytoplasmic 1 heavy chain 1 (Dync1h1), which functions as a motor for
      intracellular molecular trafficking, is required for peripheral myelination. In
      dync1h1 mutants, Schwann cell progenitors migrated to peripheral nerves but then
      failed to express Pou3f1 and Egr2 or make myelin membrane. Genetic mosaic
      experiments revealed that robust Myelin Basic Protein expression required Dync1h1
      function within both Schwann cells and axons. Finally, treatment of dync1h1
      mutants with a drug to elevate cAMP levels stimulated myelin gene expression.
      CONCLUSION: Dync1h1 is required for retrograde transport in axons and mutations
      of Dync1h1 have been implicated in axon disease. Our data now provide evidence
      that Dync1h1 is also required for efficient myelination of peripheral axons by
      Schwann cells, perhaps by facilitating signal transduction necessary for
      myelination.

PMID- 23167979
TI  - Intraoperative high-dose-rate brachytherapy using dose painting technique:
      evaluation of safety and preliminary clinical outcomes.
AB  - PURPOSE: Intraoperative radiation therapy (IORT) allows delivery of tumoricidal
      doses of radiation to areas of potential residual microscopic disease while
      minimizing doses to normal tissues. IORT using high-dose-rate (HDR) brachytherapy
      allows dose modulation and delivery of concomitant boosts to high-risk areas.
      This study describes a novel technique of HDR-IORT with dose painting (DP) (HDR
      IORT-DP) and evaluates the clinical outcomes. METHODS AND MATERIALS: Sixteen
      patients with recurrent cancers received HDR-IORT-DP at the time of radical
      resection. Of these patients, 13 had colorectal cancer, 2 had head and neck
      cancer, and 1 had a gynecologic malignancy. All received external beam radiation
      previously. Negative margin (R0) was obtained in 12 patients (75%) and
      microscopically positive margins (R1) in 4 patients (25%). RESULTS: The median
      total target and boost area were 45 and 8.5cm(2), and HDR-IORT and boost dose
      were 1500 and 1750cGy, respectively. Median followup was 14.9 months. The 2-year
      local control and overall survival were 80% and 20%, respectively. Eleven
      patients (69%) developed distant metastasis and were deceased at the time of the
      last followup. A total of 13 patients (19%) developed Grade 3 toxicity related to
      HDR-IORT; no grade 4+ toxicities were observed. CONCLUSIONS: HDR-IORT-DP
      technique is feasible, safe, and allows for dose escalation in locally advanced
      or recurrent previously irradiated tumors. To our knowledge, this is the first
      clinical report on HDR-IORT-DP. Further studies are warranted to evaluate
      efficacy in a larger patient cohort. Local control was encouraging in our
      patients.

PMID- 23167980
TI  - Sex differences in clinical presentation, severity and outcome of stroke: results
      from a hospital-based registry.
AB  - BACKGROUND AND PURPOSE: Sex related differences in cardiovascular disease and
      stroke are issues of increasing interest. The aim of this study was to evaluate
      for sex differences in clinical presentation, severity of stroke and outcome in a
      population of patients admitted to 4 public and 1 private hospitals in three
      different regions of Italy. METHODS: All hospital admissions for ischemic and
      haemorrhagic stroke (ICD-IX code 434 and 431 respectively) between January 1st
      and December 31st, 2011 at five different hospitals located in three different
      regions of Italy: Milan (North), Rome and Perugia (Center), and Palermo (South)
      have been recorded and sex-differences have been evaluated. RESULTS: A total of
      1272 stroke patients were included in the analysis: 1152 ischemic and 120
      haemorrhagic strokes, 567 women and 705 men. Compared to men, women were
      significantly older (mean age 75.2 SD 13.7 vs 71.5 SD 12.5 years, P<0.001) and
      their stroke severities at onset, measured by NIHSS, were also compared to men
      (10 SD 8 vs 8 SD 7, P<0.001). Female sex was associated with a worse functional
      prognosis measured by modified Rankin Scale score (mRS>=3), as well as in
      hospital mortality, without reaching statistical significance. There were no
      observed significant differences between sexes regarding the number of patients
      treated with thrombolytic therapy. Analysis of the distribution of risk factors
      between sexes showed a prevalence of atrial fibrillation in women (29% vs 21%,
      P=0.003). CONCLUSIONS: Both stroke severity and functional outcome were worse in
      women.

PMID- 23167981
TI  - How to manage HBeAg-negative chronic HBV infection with normal alanine
      aminotransferase levels in clinical practice?
AB  - Many HBsAg-positive/HBeAg-negative patients show normal alanine aminotransferase
      levels. However, in this group of patients two different virological and clinical
      subsets do exist: inactive HBV carriers and patients with chronic hepatitis B
      with transient virological and biochemical remission. Natural history and
      outcome, severity of liver damage and need for liver biopsy and antiviral
      treatment differ significantly between these groups of patients. It is not always
      easy to distinguish between inactive HBV carriers and patients suffering from
      HBeAg-negative chronic hepatitis with transient disease remission, as they share
      similar biochemical (normal serum ALT values) and virological (HBeAg negativity
      and low HBV DNA levels) features. In clinical practice, it is very important to
      differentiate inactive carriers from patients with chronic hepatitis B with
      spontaneous transient remission, as the former have a good prognosis with a very
      low risk of complications, while the latter have active liver disease with a high
      risk of progression to advanced hepatic fibrosis, cirrhosis and hepatocellular
      carcinoma. Thus, a careful assessment and adequate follow-up periods are needed.
      The aim of this review, written in the form of a dialog between a hepatologist
      and a newly diagnosed patient with HBV infection and normal alanine
      aminotransferase levels, is to give evidence-based suggestions for the management
      in clinical practice of HBsAg patients, on the basis of more recent international
      guidelines, covering many aspects of the condition, including advice on lifestyle
      and vaccination, indications for liver biopsy and treatment, the types and side
      effects of treatment and treatment endpoints.

PMID- 23167982
TI  - Fed batch fermentation and purification strategy for high yield production of
      Brucella melitensis recombinant Omp 28 kDa protein and its application in disease
      diagnosis.
AB  - Brucellosis is a disease caused by bacteria belonging to the genus Brucella. It
      affects cattle, goat, sheep, dog and humans. The serodiagnosis of brucellosis
      involves detection of antibodies generated against the LPS or whole cell
      bacterial extracts, however these tests lack sensitivity and specificity. The
      present study was performed to optimize the culture condition for the production
      of recombinant Brucella melitensis outer membrane protein 28 kDa protein in
      E.coli via fed batch fermentation. Expression was induced with 1.5mM isopropyl
      beta thiogalactoside and the expressed recombinant protein was purified using Ni
      NTA affinity chromatography. After fed-batch fermentation the dry cell weight of
      17.81 g/L and a purified protein yield of 210.10 mg/L was obtained. The purified
      Brucella melitensis recombinant Omp 28 kDa protein was analyzed through SDS- poly
      acrylamide gel electrophoresis and western blotting. The obtained recombinant
      protein was evaluated for its diagnostic application through Indirect ELISA using
      brucellosis suspected human sera samples. Our results clearly indicate that
      recombinant Omp28 produced via fed batch fermentation has immense potential as a
      diagnostic reagent that could be employed in sero monitoring of brucellosis.

PMID- 23167983
TI  - Swedish pediatric diabetes teams' perception of fathers' involvement: A Grounded
      Theory study.
AB  - The purpose of this study was to analyze how Swedish pediatric diabetes teams
      perceived and discussed fathers' involvement in the care of their child with type
      1 diabetes. It also aimed to discuss how the teams' attitudes towards the
      fathers' involvement developed during the data collection process. The
      Constructivist Grounded Theory design was used and data were collected during
      three repeated focus group discussions with three Swedish pediatric diabetes
      teams. The core category of the teams' perception of fathers' involvement emerged
      as: If dad attends, we are happy - if mom doesn't, we become concerned. Initially
      the teams balanced their perception of fathers' involvement on the mother's role
      as the primary caregiver. In connection with the teams' directed attention on
      fathers, in the focus group discussions, the teams' awareness of the importance
      of fathers increased. As a consequence, the team members began to encourage
      fathers' engagement in their child's care. We conclude that by increasing the
      teams' awareness of fathers as a health resource, an active health promotion
      perspective could be implemented in pediatric diabetes care. 

PMID- 23167984
TI  - Methane production by treating vinasses from hydrous ethanol using a modified
      UASB reactor.
AB  - BACKGROUND: A modified laboratory-scale upflow anaerobic sludge blanket (UASB)
      reactor was used to obtain methane by treating hydrous ethanol vinasse. Vinasses
      or stillage are waste materials with high organic loads, and a complex
      composition resulting from the process of alcohol distillation. They must
      initially be treated with anaerobic processes due to their high organic loads.
      Vinasses can be considered multipurpose waste for energy recovery and once
      treated they can be used in agriculture without the risk of polluting soil,
      underground water or crops. In this sense, treatment of vinasse combines the
      elimination of organic waste with the formation of methane. Biogas is considered
      as a promising renewable energy source. The aim of this study was to determine
      the optimum organic loading rate for operating a modified UASB reactor to treat
      vinasse generated in the production of hydrous ethanol from sugar cane molasses.
      RESULTS: The study showed that chemical oxygen demand (COD) removal efficiency
      was 69% at an optimum organic loading rate (OLR) of 17.05 kg COD/m3-day,
      achieving a methane yield of 0.263 m3/kg CODadded and a biogas methane content of
      84%. During this stage, effluent characterization presented lower values than the
      vinasse, except for potassium, sulfide and ammonia nitrogen. On the other hand,
      primers used to amplify the 16S-rDNA genes for the domains Archaea and Bacteria
      showed the presence of microorganisms which favor methane production at the
      optimum organic loading rate. CONCLUSIONS: The modified UASB reactor proposed in
      this study provided a successful treatment of the vinasse obtained from hydrous
      ethanol production.Methanogen groups (Methanobacteriales and Methanosarcinales)
      detected by PCR during operational optimum OLR of the modified UASB reactor,
      favored methane production.

PMID- 23167985
TI  - Effects of exercise before or after meal ingestion on fat balance and
      postprandial metabolism in overweight men.
AB  - It is unclear how timing of exercise relative to meal ingestion influences
      substrate balance and metabolic responses. The present study aimed to compare the
      effects of exercise performed before or after breakfast on fat balance and
      postprandial metabolism. A total of ten sedentary overweight men (aged 28.1 (SEM
      10.7) years, BMI 29.0 (SEM 2.8) kg/m2) underwent three trials in random order
      involving: (1) performing no exercise (CON), or walking for 60 min at 50% maximal
      O2 uptake either (2) before (Ex-Meal) or (3) after (Meal-Ex) consuming a
      standardised breakfast meal. In each trial an ad libitum lunch was provided 3.5 h
      after breakfast. Substrate utilisation was assessed by indirect calorimetry and
      blood was taken at regular intervals over an 8.5 h observation period. At the end
      of the observation period, fat balances in the Ex-Meal (-1043 (SEM 270) kJ) and
      Meal-Ex (-697 (SEM 201) kJ) trials were both significantly lower than CON (204
      (SEM 165) kJ) and fat balance in the Ex-Meal trial was significantly lower than
      in the Meal-Ex trial (all P , 0.0001). Compared with the CON trial, the 8.5 h
      postprandial TAG response was only significantly lowered in the Ex-Meal trial (
      17%, P = 0.025) and not in the Meal-Ex trial (-11%, P < 0.20). Both the Ex-Meal
      and Meal-Ex trials showed significantly lowered insulin responses relative to the
      CON trial (by 19 and 24%, respectively, P < 0.01 for both). There were no
      differences in lunch energy intake between trials. The present findings suggest
      that there may be an advantage for body fat regulation and lipid metabolism in
      exercising before compared with after breakfast. However, further study is needed
      to determine whether the present findings extend over the long term under free
      living conditions.

PMID- 23167986
TI  - Influence of negative affect on choice behavior in individuals with binge eating
      pathology.
AB  - Research suggests that individuals with binge eating pathology (e.g., bulimia
      nervosa (BN) and binge eating disorders (BED)) have decision making impairments
      and particularly act impulsively in response to negative affect. The aim of this
      study was to examine the influence of negative affect on choice behavior in women
      with BN and BED. Ninety women (59 with BN or BED and 31 healthy controls) watched
      a sad or control film fragment and were subsequently asked to complete a choice
      behavior task (as measured by a variation of the Bechara Gambling Task (BGT)).
      Results showed that negative affect influenced choice behavior differently in
      healthy controls and in women with BN and BED after punishment (but not after
      reward). In the context of increased negative affect, punishment was associated
      with more disadvantageous choice behavior in both BN and BED women but not in
      healthy controls, while the effect was the exact opposite in both groups after a
      decrease in negative affect. Levels of sadness were not found to influence choice
      behavior after reward in either groups. These findings suggest that emotional
      states may have a direct impact on choice behavior of individuals with binge
      eating pathology and are not only related to pathological behavior itself.

PMID- 23167987
TI  - A qualitative assessment of cross-cultural adaptation of intermediate measures
      for schizophrenia in multisite international studies.
AB  - In this substudy of the Measurement and Treatment Research to Improve Cognition
      in Schizophrenia we examined qualitative feedback on the cross-cultural
      adaptability of four intermediate measures of functional outcome (Independent
      Living Scales, UCSD Performance-Based Skills Assessment, Test of Adaptive
      Behavior in Schizophrenia, and Cognitive Assessment Interview). Feedback was
      provided by experienced English-fluent clinical researchers at 31 sites in eight
      countries familiar with medication trials. Researchers provided feedback on test
      subscales and items which were rated as having adaptation challenges. They noted
      the specific concern and made suggestions for adaptation to their culture. We
      analyzed the qualitative data using a modified Grounded Theory approach guided by
      the International Testing Commission Guidelines model for test adaptation. For
      each measure except the Cognitive Assessment Interview (CAI), the majority of
      subscales were reported to require major adaptations in terms of content and
      concepts contained in the subscale. In particular, social, financial,
      transportation and health care systems varied widely across countries-systems
      which are often used to assess performance capacity in the U.S. We provide
      suggestions for how to address future international test development and
      adaptation.

PMID- 23167988
TI  - Identification of transcriptional and phosphatase regulators as interaction
      partners of human ADA3, a component of histone acetyltransferase complexes.
AB  - ADA (alteration/deficiency in activation) 3 is a conserved component of several
      transcriptional adaptor and HAT (histone acetyltransferase) complexes that
      regulate RNA polymerase II-mediated gene expression. Within the HAT complexes
      ADA3 is associated with ADA2 and the HAT GCN5 (general control non-repressed 5).
      ADA3 plays roles in diverse cellular processes and also in malignancies by
      modulating GCN5 catalytic activity and/or by interactions with other regulators.
      To gain a better understanding of ADA3 function, we used a yeast two-hybrid
      approach to screen a human fetal cDNA library for proteins that interacted with
      hADA3 (human ADA3). We identified three novel hADA3-interacting partners, a
      transcriptional regulator, AATF (apoptosis-antagonizing transcription factor),
      and regulatory subunits of the PP1 (protein phosphatase 1) and PP2A (protein
      phosphatase 2A) [PPP1R7 (PP1 regulatory subunit 7) and PPP2R5D (PP2A 56 kDa
      regulatory subunit delta isoform) respectively]. Analysis of truncated versions
      of hADA3 indicated that the C-terminal ADA2-interacting domain was not required
      for these interactions. Fluorescent microscopy analysis and co
      immunoprecipitation provided support for the co-localization and interaction of
      hADA3 with these proteins in human cells. Expression of the interacting proteins
      altered expression of an hADA3-regulated reporter gene, suggesting functional
      consequences for the interactions. The detected interactions of hADA3 might
      extend the spectrum of mechanisms by which ADA3 can contribute to the regulation
      of gene expression and shed light on processes mediated by these newly identified
      ADA3 partners.

PMID- 23167989
TI  - Causes and management of aggression and violence in a forensic mental health
      service: perspectives of nurses and patients.
AB  - Nurses' attitudes about the causes and management of aggression affects their
      choice of intervention. We aimed to compare the attitudes held by patients and
      staff in a forensic mental health service with the Management of Aggression and
      Violence Attitudes Scale, and examine the factor validity of the tool in this
      setting by conducting a prospective comparative questionnaire survey. Staff (n =
      72) and patient (n = 98) attitudes differed to a limited extent. Confirmatory
      factor analysis refuted the previously reported structure of the tool.
      Exploratory factor analysis suggested three underlying factors related to
      modifiability of aggression, hands on management, and hands off management.
      Patients were more optimistic than nurses about the modifiability of aggressive
      behaviour. Male patients and those with diagnoses other than personality disorder
      were significantly more likely to agree about modifiability than controls.
      Forensic inpatients recognize the need for the use of a range of techniques to
      prevent and manage aggression and violence, but selected groups are most likely
      to believe that aggression is modifiable. Prevention and management of aggression
      training should emphasize the modifiability of aggressive behaviour. The
      development of measures of modifiability and management style would assist in the
      evaluation of training and would offer new avenues for research. 

PMID- 23167990
TI  - Source and origin of nerve fibres immunoreactive for substance P and calcitonin
      gene-related peptide in the normal and chronically denervated superior cervical
      sympathetic ganglion of the rat.
AB  - Immunohistochemical studies of sympathetic ganglia have indicated that the normal
      rat superior cervical ganglion contains both SP-IR and CGRP-IR fibres, and CGRP-
      and SP-immunoreactivity coexist in some fibres. In rat sympathetic ganglia
      decentralization by preganglionic denervation leads to intraganglionic increase
      of peptidergic fibres immunoreactive (IR) for substance P (SP) and calcitonin
      gene-related peptide. We explored the sources of SP- and CGRP-IR fibres in normal
      and in chronically decentralized rat SCGs. The distribution of immunoreactivities
      for CGRP and SP was determined in SCGs of normal rats and of rats following
      preganglionic denervation followed by sensory denervation. Ganglia were studied
      after short-term (2-5 days) sensory denervation, and long-term (7-16 months)
      sympathetic denervation followed by short-term (2 days) sensory denervation. To
      explore for the production of SP and CGRP by intrinsic neurones within the
      ganglion, normal and chronically decentralized SCGs were examined following
      pretreatment by local in vivo application of colchicine. Normal and chronically
      decentralized ganglia were also injected with fluorescent tracer Fluorogold for
      retrograde tracing of extrinsic fibres back to their neurones of origin. The
      observations suggest that in normal SCG in the rat the SP-IR and CGRP-IR nerve
      fibres are derived via direct links from vagus and glossopharyngeal nerves and
      the cervical plexus, or from nerve fibres running along the cervical sympathetic
      trunk, and the external carotid and the internal carotid nerves. Sensory nerve
      inputs to the rat SCG following decentralization may contribute to the low levels
      of ganglionic activation observable in the autonomic failure of multiple system
      atrophy in man.

PMID- 23167991
TI  - Genetic influences on human baroreflex regulation.
AB  - Baroreflex mechanisms have a central role in blood pressure regulation. In
      addition to disturbing cardiovascular regulation, impaired baroreflex function is
      a poor prognostic sign. However, baroreflex function is composed of several
      individual phenotypes because baroreflexes regulate heart rate and vascular tone
      in a complex way. Given the physiological and clinical relevance of human
      baroreflex function, several investigators attempted to identify "baroreflex"
      genes. Studies in monozygotic and dizygotic twins suggested that several
      components of baroreflex function may be heritable. Other studies in rare
      disorders identified putative baroreflex genes. However, data on genes affecting
      baroreflex function in the general population is scarce. Some studies described
      associations between discrete gene polymorphisms and baroreflex heart rate
      regulation. A major drawback of this approach is the large number of false
      positive results. Studies including families may be preferable to traditional
      association studies. Knowledge gathered in these large scale studies could be
      complemented by carefully conducted clinical studies in relevant genetically
      defined conditions.

PMID- 23167992
TI  - Editorial on arterial baroreflex issue.

PMID- 23167993
TI  - Resetting of the sympathetic baroreflex is associated with the onset of
      hypertension during chronic intermittent hypoxia.
AB  - Chronic intermittent hypoxia (CIH) is a model of arterial hypoxemia that
      accompanies sleep apnea and increases resting arterial pressure (AP). We examined
      the effects of 7 days of exposure to CIH on arterial baroreflex control of renal
      sympathetic nerve activity (RSNA) and heart rate (HR) in rats. Sprague-Dawley
      rats (15+/-2 weeks old) were exposed to CIH (9% oxygen for 3 min every 10 min, 8
      h per day) for 7 days (n=16) while control rats (n=18) were maintained in
      normoxia. Baroreflex regulation of RSNA and HR were estimated in Inactin
      anesthetized and artificially ventilated rats during infusions of phenylephrine
      and nitroprusside to manipulate AP. After exposure to CIH, resting mean AP was
      higher in CIH than that in control group (115+/-7 vs. 105+/-7, P<0.001). Resting
      HR did not differ between the two groups. Exposure to CIH shifted the AP-RSNA
      relationship rightward (approximately 10 mm Hg, P<0.01). CIH did not alter
      maximum gain of the baroreflex control of RSNA (-2.6+/-0.6 vs. -2.5+/-0.6
      arbitrary units (a.u.)/mm Hg) and HR (-1.8+/-0.6 vs. -1.8+/-0.7 bpm/mm Hg, CIH
      vs. control). In addition, cardiac spontaneous baroreflex sensitivity in
      conscious rats (n=8) also did not change during exposure to CIH. These results
      indicate that resetting of the sympathetic baroreflex control, rather than an
      impairment of its sensitivity, is associated with an onset of hypertension
      induced by CIH.

PMID- 23167994
TI  - Impact of different particle size distributions on anaerobic digestion of the
      organic fraction of municipal solid waste.
AB  - Particle size may significantly affect the speed and stability of anaerobic
      digestion, and matching the choice of particle size reduction equipment to
      digester type can thus determine the success or failure of the process. In the
      current research the organic fraction of municipal solid waste was processed
      using a combination of a shear shredder, rotary cutter and wet macerator to
      produce streams with different particle size distributions. The pre-processed
      waste was used in trials in semi-continuous 'wet' and 'dry' digesters at organic
      loading rate (OLR) up to 6kg volatile solids (VS) m(-3)day(-1). The results
      indicated that while difference in the particle size distribution did not change
      the specific biogas yield, the digester performance was affected. In the 'dry'
      digesters the finer particle size led to acidification and ultimately to process
      failure at the highest OLR. In 'wet' digestion a fine particle size led to severe
      foaming and the process could not be operated above 5kgVSm(-3)day(-1). Although
      the trial was not designed as a direct comparison between 'wet' and 'dry'
      digestion, the specific biogas yield of the 'dry' digesters was 90% of that
      produced by 'wet' digesters fed on the same waste at the same OLR.

PMID- 23167996
TI  - Comments on: "Recession wedge trochleoplasty as an additional procedure in the
      surgical treatment of patellar instability with major trochlear dysplasia: early
      results" by M. Thaunat, C. Bessiere, N. Pujol, P. Boisrenoult, P. Beaufils,
      published in Orthop Traumatol Surg Res 2011;97(8):833-45.

PMID- 23167995
TI  - The DNA methyltransferase inhibitor zebularine induces mitochondria-mediated
      apoptosis in gastric cancer cells in vitro and in vivo.
AB  - DNA methyltransferase (DNMT) inhibitor zebularine has been reported to potentiate
      the anti-tumor effect by reactivating the expression of tumor suppressor genes
      and apoptosis-related genes in various malignant cells. However, the apoptotic
      signaling pathway in gastric cancer cells induced by zebularine is not well
      understood. In the study, the effects of zebularine on the growth and apoptosis
      of gastric cancer cells were investigated by MTT assay, Hoechst assay, Western
      blot analysis, flow cytometric analysis of annexin V-FITC/PI staining, and TUNEL
      assay. Zebularine was an effective inhibitor of human gastric cancer cells
      proliferation in vitro and in vivo. The effects were dose dependent. A zebularine
      concentration of 50 MUM accounted for the inhibition of cell proliferation of 67%
      at 48 h. The treatment with zebularine upregulated Bax, and decreased Bcl-2
      protein. Caspase-3 was activated, suggesting that the apoptosis is mediated by
      mitochondrial pathways. Moreover, zebularine injection successfully inhibited the
      tumor growth via apoptosis induction which was demonstrated by TUNEL assay in
      xenograft tumor mouse model. These results demonstrated that zebularine induced
      apoptosis in gastric cancer cells via mitochondrial pathways, and zebularine
      might become a therapeutic approach for the treatment of gastric cancer.

PMID- 23167997
TI  - Evaluation of the WHO revised criteria for classification of clinical disease
      severity in acute adult dengue infection.
AB  - BACKGROUND: The WHO guidelines were revised recently to identify patients with
      severe dengue (SD) early. We proceeded to determine the usefulness of the warning
      signs in the new WHO guidelines in predicting SD and we have also attempted to
      define other simple laboratory parameters that could be useful in predicting SD.
      METHODS: Clinical and laboratory parameters were recorded in 184 patients in
      2011, with confirmed dengue viral infections, admitted to a medical ward in two
      tertiary care hospitals in Colombo, Sri Lanka. RESULTS: We found that the
      presence of 5 or more dengue warning signs were significantly (p=0.02) associated
      with the development of SD (odds ratio 5.14, 95% CI=1.312 to 20.16). The AST
      levels were significantly higher (p=0.0001) in patients with abdominal pain (mean
      243.5, SD +/- 200.7), when compared to those who did not have abdominal pain
      (mean 148.5, SD +/- 218.6). Lymphocyte counts <1,500 cells/mm(3) were
      significantly (p=0.005) associated with SD (odds ratio 3.367, 95% CI 1.396 to
      8.123). High AST levels were also significantly associated (p<0.0001) with SD
      (odds ratio 27.26, 95% CI 1.632 to 455.2). Platelet counts <20,000 cells/mm(3),
      were again significantly associated (p<0.001) with severe disease (odds ratio
      1.632 to 455.2, 95% CI 3.089 to 14.71). The PCR was positive in 26/84 of the
      patients and we found that the infecting serotype was DEN-1 in all 26 patients.
      CONCLUSIONS: The presence of 5 or more warning signs appears to be a predictor of
      SD. Lymphocyte counts <1,500 cells/mm(3), platelet counts <20,000/mm(3) and
      raised AST levels were associated with SD and could be used to help identify
      patients who are likely to develop SD.

PMID- 23167998
TI  - Validation of contemporary stroke and bleeding risk stratification scores in non
      anticoagulated Chinese patients with atrial fibrillation.
AB  - BACKGROUND: Risk stratification schemes assessing stroke and thromboembolism
      (stroke/TE) and bleeding relating to atrial fibrillation (AF) have largely been
      derived and validated in Western populations. We assessed risk factors that
      constitute scores for assessing stroke/TE (CHADS2, CHA2DS2-VASc) and bleeding
      (HAS-BLED), and the predictive value of these scores in a large cohort of Chinese
      patients with AF. METHODS AND RESULTS: We studied 1034 AF patients (27.1% female,
      median age 75; 85.6% non-anticoagulated) with mean follow-up of 1.9 years. On
      multivariate analysis, vascular disease was independently associated with
      stroke/TE in non-anticoagulated patients (p=0.04). In patients with a CHADS2 or
      CHA2DS2-VASc score=1, the rate of stroke/TE was 2.9% and 0.9% respectively, but
      in patients at "high risk" (scores >= 2), this rate was 4.6% and 4.5%,
      respectively. The c-statistics for predicting stroke/TE with CHADS2 and CHA2DS2
      VASc were 0.58 (p=0.109) and 0.72 (p<0.001), respectively. Compared to CHADS2,
      the use of CHA2DS2-VASc would result in a Net Reclassification Improvement (NRI)
      of 16.6% (p=0.009) and an Integrated Discrimination Improvement (IDI) of 1.1%
      (p=0.002). Cumulative survival of the patients with a CHA2DS2-VASc score>=2 was
      decreased compared to those with a CHA2DS2-VASc score 0-1 (p<0.001), but the
      CHADS2 was not predictive of mortality. There was an increased risk of major
      bleeding with increasing HAS-BLED score (c-statistic 0.61, 95% CI: 0.51-0.71,
      p=0.042). CONCLUSIONS: Vascular disease was a strong independent predictor of
      stroke/TE in Chinese patients with AF. The CHA2DS2-VASc score performed better
      than CHADS2 in predicting stroke/TE in this Chinese AF population. Cumulative
      survival of the patients at high risk with the CHA2DS2-VASc score (but not using
      CHADS2) was significantly decreased.

PMID- 23167999
TI  - Thoracic ultrasound in the differential diagnosis of severe dyspnea: a
      reappraisal.

PMID- 23168000
TI  - Fragmented QRS in lead V3 alone leading to a diagnosis of asymptomatic myocardial
      infarction.

PMID- 23168001
TI  - SCN5A mutation associated with ventricular fibrillation, early repolarization,
      and concealed myocardial abnormalities.

PMID- 23168002
TI  - "Routine" arterial echo-Doppler is not sufficient to exclude an arterial origin
      of exercise-induced proximal lower limb pain.

PMID- 23168003
TI  - Defensive active coping facilitates chronic hyperglycaemia and endothelial
      dysfunction in African men: the SABPA study.
AB  - BACKGROUND: Dissociation between behavioural defensive active coping (AC) control
      albeit physiological "loss of control" responses was associated with silent
      ischaemia and structural wall abnormalities in African men. Whether it applies to
      structural alterations and endothelial dysfunction is uncertain. We therefore
      aimed to determine AC ethnic-gender specific receiver operating characteristic
      (ROC) carotid intima media far wall (CIMTf) cut points best associated with 24-h
      BP, -silent ischaemia and glycated haemoglobin (HbA1c). METHODS: Participants
      included African and Caucasians (N=317) without pre-existing stroke or atrial
      fibrillation, aged 45 +/- 9 years. The Coping Strategy Indicator was used to
      measure AC. Ultrasound CIMTf, ambulatory BP, silent ischaemia and fasting blood
      samples were obtained. RESULTS: Between 69 and 77% of AC African men showed above
      normal diastolic BP and HbA1c levels compared to 44-48% of AC Caucasian men. In
      AC African women, 41-60% showed above normal BP, silent ischaemia and HbA1c
      levels compared to 17-44% of their Caucasian counterparts. ROC curve analyses,
      detecting optimal CIMTf cut points, ranged between 0.57 and 0.65 mm (BP) and 0.71
      and 0.74 mm (silent ischaemia) in AC ethnic-gender groups. Only HbA1C (>5.7%),
      with a sensitivity/specificity 47%/74%, after controlling for confounders,
      predicted structural alterations at an optimal cut point of 0.69 mm in AC African
      men (OR 4.5; 95% CI 2.93-18.73). CONCLUSION: Novel findings of behavioural
      resilience were apparent in the AC African female despite a high prevalence of
      risk markers. In AC males, chronic hyperglycaemia facilitated endothelial
      dysfunction, i.e. a physiological "loss of control" and susceptibility to stroke
      risk.

PMID- 23168004
TI  - A gender perspective on short- and long term mortality in ST-elevation myocardial
      infarction--a report from the SWEDEHEART register.
AB  - BACKGROUND: Previous studies of patients admitted for ST-elevation myocardial
      infarction [STEMI] have indicated that women have a higher risk of early
      mortality than do men. These studies have presented limited information on gender
      related differences in the short term and almost no information on the long term.
      METHODS AND RESULTS: We analysed a prospective, consecutively included STEMI
      population consisting of 54,146 patients (35% women). This population consists of
      almost all patients hospitalised in Sweden between January 1, 1995 and December
      31, 2006 as recorded in the SWEDEHEART register (formerly RIKS-HIA). Follow-up
      time ranged from one to 13 years (mean 4.6). Women had a lower probability of
      being given reperfusion therapy, odds ratio [OR] 0.83 (95% confidence interval
      [CI] 0.79-0.88). During the time these STEMI patients were in the hospital, 13%
      of the women and 7% of men died, multivariable adjusted OR 1.21 (95% CI 1.11
      1.32). During the follow up period, 46% of the women died as compared with 32% of
      the men. There was, however, no gender difference in age-adjusted risk of long
      term mortality (hazard ratio [HR] 0.98, 95% CI 0.95-1.01) whereas the
      multivariable adjusted risk was lower in women (HR 0.92, 95% CI 0.89-0.96). The
      long term risk of re-infarction was the same in men and women (HR 0.98, 95% CI
      0.93-1.03) whereas men in the youngest group had a higher risk than women in that
      age group (HR 0.82, 95% CI 0.72-0.94). CONCLUSION: In STEMI, women had a higher
      risk of in-hospital mortality but the long-term risk of death was higher in men.
      More studies are needed in the primary percutaneous coronary intervention (pPCI)
      era that are designed to determine why women fare worse than men after STEMI
      during the first phase when they are in hospital.

PMID- 23168005
TI  - Radiation dose surveillance using a novel automated, remote-site dose monitoring
      tool in cardiac catheterization laboratory: a feasibility study.

PMID- 23168006
TI  - Sleep disordered breathing is an independent risk factor for left atrial
      enlargement in patients with congestive heart failure.

PMID- 23168007
TI  - Population trends and inequalities in incidence and short-term outcome of acute
      myocardial infarction between 1998 and 2007.
AB  - OBJECTIVE: We studied time trends in acute myocardial infarction (AMI) incidence,
      including out-of-hospital mortality proportions and hospitalized case-fatality
      rates. In addition, we compared AMI trends by age, gender and socioeconomic
      status. METHODS: We linked the national Dutch hospital discharge register with
      the cause of death register to identify first AMI in patients >= 35 years between
      1998 and 2007. Events were categorized in three groups: 178,322 hospitalized non
      fatal, 43,210 hospitalized fatal within 28 days, and 75,520 out-of-hospital fatal
      AMI events. Time trends were analyzed using Joinpoint and Poisson regression.
      RESULTS: Since 1998, age-standardized AMI incidence rates decreased from 620 to
      380 per 100,000 in 2007 in men and from 323 to 210 per 100,000 in 2007 in women.
      Out-of-hospital mortality decreased from 24.3% of AMI in 1998 to 20.6% in 2007 in
      men and from 33.0% to 28.9% in women. Hospitalized case-fatality declined from
      2003 onwards. The annual percentage change in incidence was larger in men than
      women (-4.9% vs. -4.2%, P<0.001). Furthermore, the decline in AMI incidence was
      smaller in young (35-54 years: -3.8%) and very old (>= 85 years: -2.6%) men and
      women compared to middle-aged individuals (55-84 years: -5.3%, P<0.001). Smaller
      declines in AMI rates were observed in deprived socioeconomic quintiles Q5 and Q4
      relative to the most affluent quintile Q1 (P=0.002 and P=0.015). CONCLUSIONS:
      Substantial improvements were observed in incidence, out-of-hospital mortality
      and short-term case-fatality after AMI in the Netherlands. Young and female
      groups tend to fall behind, and socioeconomic inequalities in AMI incidence
      persisted and have not narrowed.

PMID- 23168008
TI  - Left ventricular endocardial leadless pacing brings new hope to patients with
      heart failure.

PMID- 23168010
TI  - Clinical and electrical performance of currently available MRI-safe pacing
      systems. Do all devices perform in the same way?

PMID- 23168009
TI  - Early intravenous beta-blockers in patients with acute coronary syndrome--a meta
      analysis of randomized trials.
AB  - BACKGROUND: Intravenous (IV) beta-blockade is currently a Class IIa
      recommendation in early management of patients with acute coronary syndromes
      (ACS) without obvious contraindications. METHODS: We searched the PubMed, EMBASE
      and the Cochrane Register for Controlled Clinical Trials for randomized clinical
      trials from 1965 through December, 2011, comparing intravenous beta-blockers
      administered within 12 hours of presentation of ACS with standard medical therapy
      and/or placebo. The primary outcome assessed was the risk of short-term (in
      hospital mortality-with maximum follow up duration of 90 days) all-cause
      mortality in the intervention group versus the comparator group. The secondary
      outcomes assessed were ventricular tachyarrhythmias, myocardial reinfarction,
      cardiogenic shock, and stroke. Pooled treatment effects were estimated using
      relative risk with Mantel-Haenszel risk ratio, using a random-effects model.
      RESULTS: Sixteen studies enrolling 73,396 participants met the inclusion /
      exclusion criteria. In- hospital mortality was reduced 8% with intravenous beta
      blockers, RR=0.92 (95% CI, 0.86-1.00; p=0.04) when compared with controls.
      Moreover, intravenous beta-blockade reduced the risk of ventricular
      tachyarrhythmias (RR=0.61; 95 % CI 0.47-0.79; p=0.0003) and myocardial
      reinfarction (RR=0.73, 95 % CI 0.59-0.91; p=0.004) without increase in the risk
      of cardiogenic shock, (RR=1.02; 95% CI 0.77-1.35; p=0.91) or stroke (RR=0.58; 95
      % CI 0.17-1.98; p=0.38). CONCLUSIONS: Intravenous beta-blockers early in the
      course of appropriate patients with ACS appears to be associated with significant
      reduction in the risk of short-term cardiovascular outcomes, including a
      reduction in the risk of all-cause mortality.

PMID- 23168011
TI  - Screening for Fabry disease in patients with left ventricular hypertrophy.

PMID- 23168012
TI  - QiShenYiQi Pills(r) prevent cardiac ischemia-reperfusion injury via energy
      modulation.
AB  - BACKGROUND: QiShenYiQi Pills(r) (QSYQ) is a compound Chinese medicine used in
      China for alleviating cardiac function. The present study was designed to explore
      the effect and mechanism of QSYQ on ischemia-reperfusion (I/R)-induced disorders
      in myocardial structure and function, with particularly focusing on the
      regulation of energy metabolism. METHODS: Sprague-Dawley rats, with or without
      QSYQ pretreatment, were subjected to 30 min occlusion of the left anterior
      descending coronary artery and followed by 90 min or 24h reperfusion. Myocardial
      blood flow (MBF) and cardiac function were evaluated at baseline, immediately
      after ischemia and 30, 60, 90 min, and 24h after reperfusion. Myocardial
      infarction, myocardial histology and ultrastructure were assessed. Double
      staining of alpha-cardiac actinin and terminal deoxynucleotidyl transferase
      mediated dUTP nick end labeling was conducted to assess myocardial apoptosis.
      ATP, ADP and AMP content was determined by Enzyme-Linked Immunosorbent Assay, F
      actin in myocardial cells determined by immunofluorescence microscopy and
      expression of ATP synthase alpha, ATP5D, and phosphorylated-Myosin Light Chain (P
      MLC) determined by western blotting. RESULTS: Pre-treatment with QSYQ protected
      against I/R-induced MBF decrease, myocardial infarction and apoptosis at 90 min
      and 24h after reperfusion. Moreover, I/R 90 min caused an impairment on cardiac
      function, a decrease in the ratio of ADP/ATP and AMP/ATP, accompanying with
      reduction of ATP 5D expression and increase in the expression of P-MLC,
      meanwhile, myocardium to exhibit myocardial fiber rupture, interstitial edema,
      and mitochondria swelling, all of which were significantly ameliorated by pre
      treatment with QSYQ. CONCLUSIONS: The results of the present study suggest an
      involvement of regulation of energy metabolism in the action of QSYQ to protect
      against myocardial I/R injury.

PMID- 23168013
TI  - Unexplained syncope in a patient with Brugada-like electrocardiogram. Lighting
      the dark side of underlying bradyarrhythmias.

PMID- 23168014
TI  - Endothelial progenitor cells in relation to endothelin-1 and endothelin receptor
      blockade: a randomized, controlled trial.
AB  - AIMS: Endothelial progenitor cells (EPC) represent an endogenous repair mechanism
      involving rendothelialization and neoangiogenesis. Patients with both diabetes
      and vascular disease have low numbers of circulating EPC. The endothelium-derived
      peptide, endothelin-1 (ET-1), is increased in patients with type 2 diabetes and
      vascular complications and has been suggested to contribute to endothelial
      dysfunction. Therefore, we investigated the relation between EPC and plasma ET-1
      and the effect of dual ET-1 receptor antagonist treatment. METHODS: In this
      double blind study patients with type 2 diabetes mellitus and microalbuminuria
      were randomized to treatment with the dual ETA/ETB receptor antagonist bosentan
      treatment (125mg bid; n=17) or placebo (n=19) for four weeks. Different EPC
      subpopulations were enumerated by flow cytometry using triple staining (CD34,
      CD133, KDR) at baseline at the end of treatment. Viability was assessed by 7AAD
      and Annexin-V-staining. RESULTS: Baseline ET-1 levels correlated significantly
      with C-reactive protein levels. Patients with ET-1 levels above the median value
      had higher levels of CD34(+)CD133(+) and CD34(+)KDR(+) EPC. There was no
      difference in CD34(+) and CD34(+)CD133(+)KDR(+) cells, markers of EPC apoptosis
      or circulating markers of endothelial damage between patients with ET-1 levels
      below or above the median. Four week treatment with bosentan did not change EPC
      levels. CONCLUSION: Among patients with type 2 diabetes and vascular disease,
      high plasma levels of ET-1 are associated with higher number of EPC. The
      recruitment of EPC does not seem to be regulated via ET-1 receptor activation
      since treatment with a dual ET-1 receptor blocker did not affect circulating EPC
      numbers.

PMID- 23168016
TI  - Human adipose-derived mesenchymal stromal cells injected systemically into GRMD
      dogs without immunosuppression are able to reach the host muscle and express
      human dystrophin.
AB  - Duchenne muscular dystrophy (DMD), a lethal X-linked disorder, is the most common
      and severe form of muscular dystrophies, affecting 1 in 3,500 male births.
      Mutations in the DMD gene lead to the absence of muscle dystrophin and a
      progressive degeneration of skeletal muscle. The possibility  to treat DMD
      through cell therapy has been widely investigated. We have previously shown that
      human adipose-derived stromal cells (hASCs) injected systemically in SJL mice are
      able to reach and engraft in the host muscle, express human muscle proteins, and
      ameliorate the functional  performance of injected animals without any
      immunosuppression. However, before starting clinical trials in humans many
      questions still need to be addressed in preclinical studies, in particular in
      larger animal models, when available. The best animal model to address these
      questions is the  golden retriever muscular dystrophy (GRMD) dog that reproduces
      the full spectrum of human DMD. Affected animals carry a mutation that predicts a
      premature termination codon in exon 8 and a peptide that is 5% the size of normal
      dystrophin. These dogs present clinical signs within the first  weeks and most of
      them do not survive beyond age two. Here we show the results of local and
      intravenous injections of hASCs into GRMD dogs, without immunosuppression. We
      observed that hASCs injected systemically into the dog cephalic vein are able to
      reach, engraft, and express human dystrophin  in the host GRMD dystrophic muscle
      up to 6 months after transplantation. Most importantly, we demonstrated that
      injecting a huge quantity of human mesenchymal cells in a large-animal model,
      without immunosuppression, is a safe procedure, which may have important
      applications for future therapy  in patients with different forms of muscular
      dystrophies.

PMID- 23168015
TI  - Poxvirus membrane biogenesis: rupture not disruption.
AB  - Enveloped viruses acquire their membrane from the host by budding at, or wrapping
      by, cellular membranes. Transmission electron microscopy (TEM) images, however,
      suggested that the prototype member of the poxviridae, vaccinia virus (VACV), may
      create its membrane 'de novo' with free open ends exposed in the cytosol. Within
      the frame of the German-wide priority programme we re-addressed the biogenesis
      and origin of the VACV membrane using electron tomography (ET), cryo-EM and lipid
      analysis of purified VACV using mass spectrometry (MS). This review discussed how
      our data led to a model of unconventional membrane biogenesis involving membrane
      rupture and the generation of a single open membrane from open membrane
      intermediates. Lipid analyses of purified virus by MS suggest an ER origin with a
      relatively low cholesterol content compared with whole cells, confirming
      published data. Unlike previous reports using thin-layer chromatography, no
      depletion of phosphatidylethanolamine was detected. We did detect, however, an
      enrichment for phosphatidic acid, diacylglycerol and phosphatidylinositol in the
      virion. Our data are discussed in the light of other pathogens that may
      requirecellular membrane rupture during their intracellular life cycle.

PMID- 23168017
TI  - Targeting bacterial integration host factor to disrupt biofilms associated with
      cystic fibrosis.
AB  - BACKGROUND: This study aims to identify whether the bacterial protein,
      Integration Host Factor (IHF), is present within sputum solids collected from
      cystic fibrosis (CF) patients and thus might contribute to the structural
      stability of biofilms within the lungs. METHODS: The presence of IHF in sputum
      was determined by immunohistochemistry. The role of IHF in stabilizing biofilms
      within sputum was tested in vitro wherein anti-IHF was used to attempt to
      dissolve sputum solids. RESULTS: Thirty-seven of 44 sputum samples (84%) were
      positive for anti-IHF staining. Treatment with anti-IHF or DNase of 6
      representative samples, dissolved sputum solids significantly better than
      treatment with normal saline in vitro, and strong synergism was observed when
      these agents were used in combination. CONCLUSIONS: IHF was detected in the
      majority of sputum samples from patients with CF and in vitro treatment with anti
      IHF induced dissolution of sputum solids. These data support further
      investigation of IHF as a potential therapeutic target for patients with CF.

PMID- 23168018
TI  - A rhodamine-labeled citalopram analogue as a high-affinity fluorescent probe for
      the serotonin transporter.
AB  - A novel fluorescent ligand was synthesized as a high-affinity, high specificity
      probe for visualizing the serotonin transporter (SERT). The rhodamine fluorophore
      was extended from an aniline substitution on the 5-position of the
      dihydroisobenzofuran ring of citalopram (2, 1-(3-(dimethylamino)propyl)-1-(4
      fluorophenyl)-1,3-dihydroisobenzofuran-5-carbonitrile), using an ethylamino
      linker. The resulting rhodamine-labeled ligand 8 inhibited [(3)H]5-HT uptake in
      COS-7 cells (K(i)=225 nM) with similar potency to the tropane-based JHC 1-064
      (1), but with higher specificity towards the SERT relative to the transporters
      for dopamine and norepinephrine. Visualization of the SERT with compound 8 was
      demonstrated by confocal microscopy in HEK293 cells stably expressing EGFP-SERT.

PMID- 23168019
TI  - Isosteric analogs of lenalidomide and pomalidomide: synthesis and biological
      activity.
AB  - A series of analogs of the immunomodulary drugs lenalidomide (1) and pomalidomide
      (2), in which the amino group is replaced with various isosteres, was prepared
      and assayed for immunomodulatory activity and activity against cancer cell lines.
      The 4-methyl and 4-chloro analogs 4 and 15, respectively, displayed potent
      inhibition of tumor necrosis factor-alpha (TNF-alpha) in LPS-stimulated hPBMC,
      potent stimulation of IL-2 in a human T cell co-stimulation assay, and anti
      proliferative activity against the Namalwa lymphoma cell line. Both of these
      analogs displayed oral bioavailability in rat.

PMID- 23168020
TI  - Deep brain stimulation in Parkinson's disease: reconciliation of evidence-based
      medicine with clinical practice.

PMID- 23168021
TI  - Subthalamic nucleus versus globus pallidus bilateral deep brain stimulation for
      advanced Parkinson's disease (NSTAPS study): a randomised controlled trial.
AB  - BACKGROUND: Patients with advanced Parkinson's disease often have rapid swings
      between mobility and immobility, and many respond unsatisfactorily to adjustments
      in pharmacological treatment. We assessed whether globus pallidus pars interna
      (GPi) deep brain stimulation (DBS) gives greater functional improvement than does
      subthalamic nucleus (STN) DBS. METHODS: We recruited patients from five centres
      in the Netherlands who were aged 18 years or older, had idiopathic Parkinson's
      disease, and had, despite optimum pharmacological treatment, at least one of the
      following symptoms: severe response fluctuations, dyskinesias, painful dystonias,
      or bradykinesia. By use of a computer-generated randomisation sequence, we
      randomly assigned patients to receive either GPi DBS or STN DBS (1:1), applying a
      minimisation procedure according to drug use (levodopa equivalent dose <1000 mg
      vs >=1000 mg) and treatment centre. Patients and study assessors (but not those
      who assessed adverse events) were masked to treatment allocation. We had two
      primary outcomes: functional health as measured by the weighted Academic Medical
      Center Linear Disability Scale (ALDS; weighted by time spent in the off phase and
      on phase) and a composite score for cognitive, mood, and behavioural effects up
      to 1 year after surgery. Secondary outcomes were symptom scales, activities of
      daily living scales, a quality-of-life questionnaire, the occurrence of adverse
      events, and drug use. We used the intention-to-treat principle for all analyses.
      This trial is registered with www.controlled-trials.com, number ISRCTN85542074.
      FINDINGS: Between Feb 1, 2007, and March 29, 2011, we enrolled 128 patients,
      assigning 65 to GPi DBS and 63 to STN DBS. We found no statistically significant
      difference in either of our primary outcomes: mean change in weighted ALDS (3.0
      [SD 14.5] in the GPi group vs 7.7 [23.2] in the STN group; p=0.28) and the number
      of patients with cognitive, mood, and behavioural side-effects (36 [58%] of 62
      patients in the GPi group vs 35 [56%] of 63 patients in the STN group; p=0.94).
      Secondary outcomes showed larger improvements in off-drug phase in the STN group
      compared with the GPi group in the mean change in unified Parkinson's disease
      rating scale motor examination scores (20.3 [16.3] vs 11.4 [16.1]; p=0.03), the
      mean change in ALDS scores (20.3 [27.1] vs 11.8 [18.9]; p=0.04), and medication
      (mean levodopa equivalent drug reduction: 546 [SD 561] vs 208 [521]; p=0.01). We
      recorded no difference in the occurrence of adverse events between the two
      groups. Other secondary endpoints showed no difference between the groups.
      INTERPRETATION: Although there was no difference in our primary outcomes, our
      findings suggest that STN could be the preferred target for DBS in patients with
      advanced Parkinson's disease. FUNDING: Stichting Internationaal Parkinson Fonds,
      Prinses Beatrix Fonds, and Parkinson Vereniging.

PMID- 23168022
TI  - Oxysterol changes along with cholesterol and vitamin D changes in adult
      phenylketonuric patients diagnosed by newborn mass-screening.
AB  - BACKGROUND: Phenylketonuria (PKU) possibly leads to hypocholesterolemia and
      lowered vitamin D (VD) status. Metabolism of oxysterols linking with those of
      cholesterol and VD has never been examined in PKU. METHODS: Blood oxysterols
      along with blood phenylalanine, lipids and VD were examined for 33 PKU adults
      aged 21-38 years and 20 age-matched healthy controls. RESULTS: Total- and low
      density cholesterols, and 25-hydroxy VD(3) were decreased significantly in the
      PKU group (cholesterols, 10% decrease; 25-hydroxy VD(3) 35% decrease vs. the
      control group). 24S-hydroxycholesterol (24S-OHC) eliminating brain cholesterol,
      and 27-OHC and 7alpha-hydroxycholesterol (7alpha-OHC) representing peripheral and
      hepatic cholesterol elimination, respectively, were significantly decreased in
      PKU group: 24S-OHC, 25% decrease, p<.01; 27-OHC and 7alpha-OHC, 35-40% decrease,
      p<.001. 7beta-Hydroxycholesterol (7beta-OHC) reflecting oxidative stress was
      increased significantly in PKU group (p<.05). 7alpha-OHC and 27-OHC levels in PKU
      group always showed similar values, regardless of other parameters while the 24S
      OHC and 7beta-OHC levels decreased and increased, respectively, showing
      significant correlations with phenylalanine level (p<.005). 27-OHC level showed a
      significant positive correlation with the 25-hydroxy VD(3) level in this group
      (p<.001). CONCLUSION: Blood oxysterol changes predominate over blood cholesterol
      changes and influence on VD status in adult PKU patients.

PMID- 23168023
TI  - Intestinal parasite infections in immigrant children in the city of Rome, related
      risk factors and possible impact on nutritional status.
AB  - BACKGROUND: Parasitic diseases can represent a social and economic problem among
      disadvantaged people--even in developed countries. Due to the limited data
      available concerning Europe, the aims of the present study were to evaluate the
      presence of parasites in immigrant children and the risk factors favouring the
      spread of parasites. Subsequently, the possible correlation between nutritional
      status and parasitic infections was also investigated. FINDINGS: A convenience
      sample of two hundred and forty seven immigrant children (aged 0-15) attending
      the Poliambulatorio della Medicina Solidale in Rome was examined. Data were
      collected using structured questionnaires, and parasitological and anthropometric
      tests were applied. Chi-squared test and binary logistic multiple-regression
      models were used for statistical analysis. Thirty-seven children (15%) tested
      positive to parasites of the following species: Blastocystis hominis, Entamoeba
      coli, Giardia duodenalis, Enterobius vermicularis, Ascaris lumbricoides and
      Strongyloides stercoralis. A monospecific infection was detected in 30 (81%) out
      of 37 parasitized children, while the others (19%) presented a polyparasitism.
      The major risk factors were housing, i.e. living in shacks, and cohabitation with
      other families (p<0.01). Children classified in the lower height Z-scores had a
      significantly greater prevalence of parasites (30.9%) than the others (p<0.01).
      CONCLUSIONS: This study shows that parasite infection in children is still quite
      common, even in a developed country and that children's growth and parasitism may
      be related. Extensive improvements in the living, social and economic conditions
      of immigrants are urgently needed in order to overcome these problems.

PMID- 23168024
TI  - History and design considerations for arthroplasty around the wrist.
AB  - The history and evolution of both soft tissue and implant arthroplasty about the
      wrist are discussed, including carpometacarpal, radiocarpal, and distal
      radioulnar joints. Technical considerations for arthroplasty are reviewed,
      including factors affecting implant osseointegration, implant
      articulation/constraint, and management of complications.

PMID- 23168025
TI  - Ligament reconstruction and tendon interposition for thumb basal arthritis.
AB  - Arthritis at the base of the thumb is common and debilitating. Arthroplasty has
      evolved over 3 decades to become a highly refined surgical procedure, with
      excellent results. This article summarizes the history, method, and expected
      results of basal joint arthroplasty, and the authors describe their method of
      ligament reconstruction and tendon interposition for thumb basal arthritis.

PMID- 23168026
TI  - Trapezium resection with mersilene suspension sling.
AB  - The reason there are numerous techniques for thumb carpometacarpal arthroplasty
      is that none of them are perfect. Sometimes the simplest procedures work best.
      This article presents a simple alternative, using a readily available suture to
      stabilize the thumb after resection of the trapezium, with long-term success.

PMID- 23168027
TI  - Trapezium prosthetic arthroplasty (silicone, Artelon, metal, and pyrocarbon).
AB  - Trapezium prosthetic arthroplasty has been utilized to treat basal joint
      arthritis for nearly five decades in an attempt to mitigate some of the potential
      disadvantages of trapeziectomy while preserving range of motion. Implant
      arthroplasty seeks to preserve joint biomechanics, avoids metacarpal subsidence,
      and should provide immediate stability. These benefits may lead to improvements
      in strength, durability, and a decrease in metacarpophalangeal joint
      hyperextension which can occur subsequent to metacarpal shortening. First
      generation implants were primarily silicone trapezial spacers. While the use of
      these implants has been curtailed by their association with silicone synovitis,
      they still remain an option for low demand, rheumatoid patients. More recently
      developed synthetic spacers such as Artelon interposition arthroplasties have had
      results inferior to more established procedures including trapeziectomy. A
      variety of metal total joint prostheses have been developed and some of the more
      recent designs have shown good short-term outcomes. There are a number of
      different pyrocarbon implants that have become more recently available which
      range from trapezial substitution to non-anatomic hemiarthroplasty. Pyrocarbon
      arthroplasty offers a number theoretical advantages however early results have
      been mixed and further long term data is required.

PMID- 23168028
TI  - Arthroplasty of the scaphoid-trapezium-trapezoid and carpometacarpal joints.
AB  - Resection arthroplasty is an old, and yet reliable, solution for the isolated
      osteoarthritis (OA) of some joints of the hand. With complication low rates, this
      technically undemanding option is ideal for scapho-trapezial-trapezoidal joint
      OA, as well as for the OA of the carpometacarpal joints of the fingers. This
      paper reviews its indications, surgical technique, and results.

PMID- 23168029
TI  - Proximal row carpectomy.
AB  - Proximal row carpectomy (PRC) is a motion-preserving treatment for the
      degenerated wrist. PRC provides painless wrist range of motion with few
      complications. PRC treats specifically scapholunate advanced collapse, scaphoid
      non-union advanced collapse, chronic perilunate dislocations, and Kienbock's
      disease. The best candidates are older than 35 with an intact capitate head and
      lunate facet of the distal radius. Proximal row carpectomy provides satisfactory
      postoperative wrist range of motion and grip strength with few complications,
      especially when there is no capitolunate arthrosis. Postoperative progressive
      changes at the radiocapitate articulation have been documented, yet these changes
      tend to remain asymptomatic.

PMID- 23168030
TI  - Wrist arthroplasty: partial and total.
AB  - Although arthrodesis is the treatment preferred by most surgeons for severe wrist
      arthritis, some degree of functional impairment occurs from the resulting loss of
      motion, especially when multiple joints in the extremity are affected by
      arthritis. Total wrist arthroplasty may enhance the performance of daily
      activities and it is usually preferred by patients over arthrodesis. The newer
      generation of wrist prostheses has demonstrated improved performance and
      durability in properly selected patients. This article provides a review of the
      history, indications, techniques, and outcomes of wrist arthroplasty.

PMID- 23168031
TI  - Prosthetic arthroplasty of the distal radioulnar joint: historical perspective
      and 24-year follow-up.
AB  - This is a report of the first prosthetic hemiarthroplasty and full arthroplasty,
      designed and implanted for the distal radioulnar joint in 1988. Two case reports
      are presented, with follow-up of 24 years. Experience and problems in the design
      of both a hemiarthroplasty and total prosthetic arthroplasty are described, in
      the hope that future developments may avoid past failures.

PMID- 23168032
TI  - Implant arthroplasty for treatment of ulnar head resection-related instability.
AB  - Resection of the ulnar head in cases of debilitating pain owing to arthrosis of
      the distal radioulnar joint can provide satisfying relief. However, there is
      mounting evidence that pain with heavier use, instability, and torque-generating
      weakness in more active individuals may result in less satisfying outcomes.
      Implant arthroplasty can provide a means to stabilize the radius to the ulna
      after ulnar head resection, but it requires significant attention to requisite
      soft tissue stabilization and alignment of the distal radius to the implant to be
      successful.

PMID- 23168033
TI  - Distal radioulnar joint constrained arthroplasty.
AB  - This article presents the use of a constrained total distal radioulnar joint
      replacement with its indications, contraindications, pearls, and pitfalls. The
      distal radioulnar joint is a complex articulation that carries weight while
      allowing vector changes without interfering with its function. The total distal
      radioulnar joint is a solution to those cases with absence of the sigmoid notch,
      poor soft tissue, or too much ulnar bone resected. The ability of patients to
      return to regular activities is documented, with a 5-year follow-up.

PMID- 23168034
TI  - Rehabilitation following thumb CMC, radiocarpal, and DRUJ arthroplasty.
AB  - Hand therapy is essential after arthroplasty around the wrist. This article
      includes therapy guidelines and goals after surgical reconstruction of the thumb
      carpometacarpal joint, radiocarpal joint, and distal radioulnar joint. Typical
      concerns and treatment options are addressed. Tables and figures are included to
      guide the hand therapist in the process of returning this patient population to
      pain-free function.

PMID- 23168035
TI  - A carpal ligament substitute part 1: polyester suture.
AB  - We have searched for a synthetic substitute for the carpal ligaments, which would
      be widely available and easy to use. Four loops of 2-0 polyester fiber suture
      (Mersilene) were found to exceed the ultimate tensile strength of the
      scapholunate interosseous ligament. This construct approximates a normal ligament
      stress/strain curve and can theoretically facilitate fibrous tissue ingrowth. It
      is readily available, easy to handle, and inexpensive. Based on these findings,
      we recommend the use of polyester suture in the reconstruction of carpal and
      other ligaments.

PMID- 23168036
TI  - A carpal ligament substitute part II: polyester suture for scapho-lunate and
      triqueto-lunate ligament reconstruction.
AB  - Carpal ligaments are commonly injured and may lead to pain and disability. These
      ligaments are very difficult to repair, and the results are unpredictable; as a
      result, treatment options abound. A novel approach is presented here using a
      polyester suture, aiming to substitute these ligaments' function, rather than to
      repair them.

PMID- 23168040
TI  - BAMBI (BMP and activin membrane-bound inhibitor) protects the murine heart from
      pressure-overload biomechanical stress by restraining TGF-beta signaling.
AB  - Left ventricular (LV) pressure overload is a major cause of heart failure.
      Transforming growth factors-beta (TGF-betas) promote LV remodeling under
      biomechanical stress. BAMBI (BMP and activin membrane-bound inhibitor) is a
      pseudoreceptor that negatively modulates TGF-beta signaling. The present study
      tests the hypothesis that BAMBI plays a protective role during the adverse LV
      remodeling under pressure overload. The subjects of the study were BAMBI knockout
      mice (BAMBI(-/-)) undergoing transverse aortic constriction (TAC) and patients
      with severe aortic stenosis (AS). We examined LV gene and protein expression of
      remodeling-related elements, histological fibrosis, and heart morphology and
      function. LV expression of BAMBI was increased in AS patients and TAC-mice and
      correlated directly with TGF-beta. BAMBI deletion led to a gain of myocardial TGF
      beta signaling through canonical (Smads) and non-canonical (TAK1-p38 and TAK1
      JNK) pathways. As a consequence, the remodeling response to pressure overload in
      BAMBI(-/-) mice was exacerbated in terms of hypertrophy, chamber dilation,
      deterioration of long-axis LV systolic function and diastolic dysfunction.
      Functional remodeling associated transcriptional activation of fibrosis-related
      TGF-beta targets, up-regulation of the profibrotic micro-RNA-21, histological
      fibrosis and increased metalloproteinase-2 activity. Histological remodeling in
      BAMBI(-/-) mice involved TGF-betas. BAMBI deletion in primary cardiac fibroblasts
      exacerbated TGF-beta-induced profibrotic responses while BAMBI overexpression in
      NIH-3T3 fibroblasts attenuated them. Our findings identify BAMBI as a critical
      negative modulator of myocardial remodeling under pressure overload. We suggest
      that BAMBI is involved in negative feedback loops that restrain the TGF-beta
      remodeling signals to protect the pressure-overloaded myocardium from
      uncontrolled extracellular matrix deposition in humans and mice.

PMID- 23168042
TI  - Photoaging behavior of 3-D colloidal photonic crystals.
AB  - Since most polymers are not inherently stable to light, their photochemical
      behavior remains a subject of constant interest. In this study, we investigated
      the photoaging behavior of polymeric colloidal photonic crystal films. As a
      consequence of photochemical reactions containing chain-scission, photoaging
      induced morphological changes in the film surface including changes in the size,
      surface roughness, shape, and packing structure of PS particles. These structural
      modifications came about the deterioration of optical properties (photonic
      bandgap) during photoaging. Based on our results and observations, a plausible
      correlation between the evolutions of the optical properties and the structural
      modifications during photoaging was established. Finally, the compositional
      modifications of the surface based on oxygen incorporation behavior caused by the
      photooxidation process are discussed based on the ATR-FTIR and XPS analyses.

PMID- 23168043
TI  - The role of glutathione on shape control and photoelectrical property of cadmium
      sulfide nanorod arrays.
AB  - Well-aligned CdS nanorod arrays (CdS NRs) with ~100 nm in diameter and ~700 nm in
      length were fabricated on FTO (fluorine-doped tin oxide) substrate by using
      glutathione as capping agents. The growth of CdS NRs was studied in details by
      exploring the roles of each active binding group in glutathione. The thiol group
      in glutathione plays an important role in forming a compact CdS nanocrystal film,
      upon which the nanorods grow subsequently via the synergetic effect of thiol and
      dicarboxyl groups in glutathione. The influence of surface passivation with
      glutathione on the photoelectrical property of CdS NRs was also tested. The
      results revealed that glutathione ligands encapsulated in the surfaces of CdS NRs
      act as insulating barriers between CdS NRs and solution, hindering charge
      transport. Hybrid photovoltaic cells of FTO/CdS NRs/P3HT (poly(3
      hexylthiophene))/Au were then assembled. The performance of the photovoltaic
      devices was increased with increasing the length of the as-prepared CdS nanorods
      and further enhanced to the highest efficiency of 0.373% after the thermal
      sulfuration treatment.

PMID- 23168041
TI  - Somatic evolution of head and neck cancer - biological robustness and latent
      vulnerability.
AB  - Despite recent advancements in multidisciplinary treatments, the overall survival
      and quality of life of patients with advanced head and neck squamous cell
      carcinoma (HNSCC) have not improved significantly over the past decade. Molecular
      targeted therapies, which have been addressed and advanced by the concept of
      "oncogene addiction", have demonstrated only limited successes so far. To explore
      a novel clue for clinically effective targeted therapies, we analyzed the
      molecular circuitry of HNSCC through the lens that HNSCC is an evolving system.
      In the trajectory of this somatic evolution, HNSCC acquires biological robustness
      under a variety of selective pressures including genetic, epigenetic, micro
      environmental and metabolic stressors, which well explains the major mechanism of
      "escaping from oncogene addiction". On the other hand, this systemic view appears
      to instruct us approaches to target latent vulnerability of HNSCC that is masked
      behind the plasticity and evolvability of this complex adaptive system.

PMID- 23168044
TI  - A comparative study of in-flow and micro-patterning biofunctionalization
      protocols for nanophotonic silicon-based biosensors.
AB  - Reliable immobilization of bioreceptors over any sensor surface is the most
      crucial step for achieving high performance, selective and sensitive biosensor
      devices able to analyze human samples without the need of previous processing.
      With this aim, we have implemented an optimized scheme to covalently
      biofunctionalize the sensor area of a novel nanophotonic interferometric
      biosensor. The proposed method is based on the ex-situ silanization of the
      silicon nitride transducer surface by the use of a carboxyl water soluble silane,
      the carboxyethylsilanetriol sodium salt (CTES). The use of an organosilane stable
      in water entails advantages in comparison with usual trialkoxysilanes such as
      avoiding the generation of organic waste and leading to the assembly of compact
      monolayers due to the high dielectric constant of water. Additionally, cross
      linking is prevented when the conditions (e.g. immersion time, concentration of
      silane) are optimized. This covalent strategy is followed by the bioreceptor
      linkage on the sensor area surface using two different approaches: an in-flow
      patterning and a microcontact printing using a biodeposition system. The
      performance of the different bioreceptor layers assembled is compared by the real
      time and label-free immunosensing of the proteins BSA/mAb BSA, employed as a
      model molecular pair. Although the results demonstrated that both strategies
      provide the biosensor with a stable biological interface, the performance of the
      bioreceptor layer assembled by microcontact printing slightly improves the
      biosensing capabilities of the photonic biosensor.

PMID- 23168045
TI  - Carbon dioxide (CO2) absorption behavior of mixed matrix polymer composites
      containing a flexible coordination polymer.
AB  - Mixed matrix membranes (MMMs) comprised of metal organic frameworks (MOFs)
      dispersed in organic polymers are popular materials under study for potential
      applications in gas separations. However, research on MMMs containing
      structurally dynamic sorbents known as flexible MOFs has only very recently
      appeared in the literature. The thermodynamic requirements of the structure
      transition between the low porosity and high porosity phases of flexible MOFs may
      provide a mechanism for high adsorption selectivity in these materials. A
      fundamental question in MMMs containing flexible MOFs is how the constraint of
      the polymer matrix on the intrinsic expansion of the flexible MOF particles that
      occurs during gas adsorption might affect the thermodynamics of this structural
      phase transition and influence the gas adsorption properties of the embedded MOF.
      To investigate the fundamental nature of this flexible MOF-polymer interface,
      thin films of ~20 um thickness were prepared using the flexible linear chain
      coordination polymer catena-bis(dibenzoylmethanato)-(4,4'bipyridyl)nickel(II)
      "Ni(Bpy)(DBM)(2)" embedded as 35 wt% dispersions in Matrimid(r), polystyrene, and
      polysulfone. The adsorption of CO(2) in the polymers and embedded particles was
      studied using in situ ATR-FTIR spectroscopy and variable temperature volumetric
      CO(2) adsorption/desorption isotherms. Interestingly, no effect of the polymer
      matrix on the gas adsorption behavior of the embedded Ni(Bpy)(DBM)(2) particles
      was observed. The composite samples all showed the same threshold pressures for
      CO(2) absorption and desorption hysteresis associated with the structural phase
      change in the polymer embedded Ni(Bpy)(DBM)(2) particles as was observed in the
      pristine polycrystalline sample. The current results contrast those recently
      reported for a MMM containing the flexible MOF "NH(2)-MIL-53" where a significant
      increase in the threshold pressure for CO(2) adsorption associated with the
      structural phase change of the MOF was observed in the MMM as compared to the
      isolated MOF. The conflicting behaviors in these two systems are rationalized
      from the large differences in unit cell expansions between the two MOFs during
      the CO(2) adsorption process.

PMID- 23168046
TI  - Evaluation of lymphocyte populations in dogs naturally infected by Ehrlichia
      canis with and without clinical signs.
AB  - Immune response elicited by the host during ehrlichial infections could influence
      the clinical signs and laboratory and pathological findings. Twenty-eight dogs
      naturally infected by Ehrlichia canis were included in this study. Twenty of them
      presented only laboratory findings traditionally associated with canine monocytic
      ehrlichiosis (CME), whilst 8 dogs also showed clinical signs classically
      associated with CME (pale mucous membranes, fever, lymphadenopathy, weight loss,
      anorexia, lethargy or signs attributable to bleeding tendencies). A
      multiparametric flow cytometric study was performed to analyze the distribution
      of the main lymphocyte subsets (T, Th, Tc, B, and those that express MHC class
      II) in the peripheral blood. Statistically significant differences between dogs
      naturally infected by E. canis in a clinical or subclinical stage were not
      detected when evaluating lymphocyte subsets in peripheral blood samples. Dogs
      with clinical signs showed lower relative and absolute values of B lymphocytes
      than dogs without clinical signs, although the differences were not statistically
      significant.

PMID- 23168047
TI  - Effects of tick saliva on the migratory and invasive activity of Saos-2
      osteosarcoma and MDA-MB-231 breast cancer cells.
AB  - In previous studies we showed that tick saliva modulates the migratory activity
      of cells involved in the wound healing response. Since cell migration is a
      prerequisite for tumor invasion and metastasis, we examined the effects of tick
      saliva on the migratory and invasive activity of Saos-2 osteosarcoma and MDA-MB
      231 (MB-231) breast cancer cells and the potential signaling pathways that may be
      affected. Saliva inhibited basal and agonist-induced Saos-2 and MB-231 migration
      and invasion through a matrigel-coated filter. In the Saos-2 cells, saliva
      suppressed epidermal growth factor (EGF)-activation of Akt/Protein Kinase B,
      however, only basal extracellular signal-regulated kinase (ERK) activity was
      affected in MB-231 cells. EGF receptor (EGFR) overexpression masked the effect of
      saliva on MB-231 cells, but its ability to inhibit MB-231 migration was enhanced
      by the EGFR inhibitor PD 168393 and MEK inhibitor U0126. Our data indicate that
      the mechanisms ticks have evolved to regulate the wound healing response have
      generalized effects on the migratory and invasive activities of metastatic cancer
      cells.

PMID- 23168048
TI  - Mediterranean spotted fever in the Trakya region of Turkey.
AB  - Mediterranean spotted fever (MSF) is caused by a tick-borne pathogen, Rickettsia
      conorii subsp. conorii, belonging to the spotted fever group (SFG) rickettsiae.
      The aim of the present study was to evaluate the cases with confirmed diagnosis
      of MSF from 2003 to 2009 in the Trakya region of Turkey. Patients with high
      fever, maculopapular rash (involving the palms or soles) and/or a black
      inoculation eschar at the site of the tick bite (tache noire) were included in
      the study. Before doxycycline treatment, skin biopsy specimens, preferably from
      the eschar or from the maculopapular rash, were obtained for DNA extraction.
      Immunofluorescence assay (IFA) was performed to detect IgM and IgG antibodies
      against R. conorii in acute and convalescent sera. Afterwards, a standard PCR
      reaction using primers suitable for hybridisation within the conserved region of
      genes coding for outer membrane protein A (ompA) and citrate synthase (gltA) and
      DNA sequencing were performed. There were 128 patients with confirmed MSF
      diagnosis. Using IFA, seroconversion or a fourfold or greater rise in titre was
      observed in 97 (77%) patients, whereas a single high titre was demonstrated in 16
      (12.7%) patients. According to PCR analysis, 77 (72.6%) of 106 biopsy samples
      showed positive results. Of these, 58 (73%) of 79 biopsy specimens were from the
      eschar and 19 (70%) of 27 specimens were from the maculopapular rash. No
      significant difference was found between the rate of positive skin biopsies taken
      from the eschar and the maculopapular rash. DNA sequence analysis was performed
      to all PCR-positive cases, and R. conorii conorii (type strain: Malish, ATCC VR
      613) was detected in each of them. MSF is prevalent, but has been underdiagnosed
      and underreported so far in Turkey. It is a potentially severe and even fatal
      disease resembling viral haemorrhagic fevers that has to be included in the
      differential diagnosis of febrile illness associated with thrombocytopenia, even
      in the absence of an eschar or a tick bite. While IFA allows for retrospective
      diagnosis in MSF, advanced molecular techniques provide the rapid detection of
      rickettsia in all skin samples, including eschar and maculopapular rash.

PMID- 23168049
TI  - First molecular detection of Ehrlichia canis and Anaplasma platys in ticks from
      dogs in Cebu, Philippines.
AB  - Ehrlichia canis infection of dogs in the Philippines has been detected by
      serological and peripheral blood smear examination methods, but not by molecular
      means. Anaplasma platys infection in dogs has not yet been officially reported,
      although it is suspected to occur in the country. Thus, sensitive and specific
      molecular techniques were used in this study to demonstrate the presence of both
      E. canis and A. platys in the Philippines. A total of 164 Rhipicephalus
      sanguineus ticks was collected from 36 dogs. Seven tick samples were found
      positive with E. canis and one sample with A. platys. To further characterize
      these pathogens, molecular analyses based on citrate synthase and heat-shock
      operon genes were also performed. Philippine strains were found to be not
      divergent from strains from other countries. The present results are the first
      molecular detection and analyses of E. canis and A. platys in ticks from dogs in
      the Philippines.

PMID- 23168050
TI  - Brazilian spotted fever: real-time PCR for diagnosis of fatal cases.
AB  - Suspicion of Brazilian spotted fever (BSF) should occur in endemic regions upon
      surveillance of the acute febrile icteric hemorrhagic syndrome (AFIHS). However,
      limitations associated with currently available laboratory tests pose a challenge
      to early diagnosis, especially in fatal cases. Two real-time PCR (qPCR) protocols
      were evaluated to diagnose BSF in 110 fatal AFIHS cases, collected in BSF-endemic
      regions in 2009-2010. Of these, 24 were positive and 86 negative by indirect
      immunofluorescence (IFA) assay (cut-off IgG and/or IgM >= 128). DNA from these
      samples was used in the qPCR protocols: one to detect Rickettsia spp. (citrate
      synthase gene) and another to determine spotted fever group (SFG) Rickettsia
      species (OmpA gene). Of the 24 IFA-positive samples, 5 (21%) were positive for
      OmpA and 9 (38%) for citrate synthase. In the IFA-negative group (n=86), OmpA and
      citrate synthase were positive in 23 (27%) and 27 (31%), respectively. These
      results showed that the 2 qPCR protocols were about twice as sensitive as the IFA
      test alone (93% concordance). In conclusion, qPCR is a sensitive method for the
      diagnosis of fatal BSF cases and should be considered for routine surveillance of
      AFIHS in places like Brazil, where spotted fever-related lethality is high and
      other endemic diseases like dengue and leptospirosis can mislead diagnosis.

PMID- 23168051
TI  - Molecular survey of Rickettsia, Ehrlichia, and Anaplasma infection of domestic
      cats in Japan.
AB  - The prevalence of Rickettsia, Ehrlichia, and Anaplasma in 1764 DNA samples
      extracted from feline peripheral blood from all 47 prefectures in Japan was
      evaluated by screening real-time PCR, genus-specific PCR, and DNA nucleotide
      sequencing. The survey revealed that all cats were negative for Rickettsia
      infection. Two cats were positive for Ehrlichia or Anaplasma based on the
      screening PCR assay. Nucleotide sequence analysis of the partial 16S rRNA
      including the divergent region near the 3'-end revealed that the 2 positives were
      most similar to Anaplasma bovis with percent identities of 99.8% and 99.2%. This
      was the first detection of A. bovis DNA fragments in cats. Although these 2 cats
      showed stomatitis, both were also infected with feline immunodeficiency virus.
      The relationship between A. bovis carriage and clinical disease is not yet
      understood.

PMID- 23168053
TI  - Vectors of rickettsiae in Africa.
AB  - Vector-borne diseases are caused by parasites, bacteria, or viruses transmitted
      by the bites of hematophagous arthropods. In Africa, there has been a recent
      emergence of new diseases and the re-emergence of existing diseases, usually with
      changes in disease epidemiology (e.g., geographical distribution, prevalence, and
      pathogenicity). In Africa, rickettsioses are recognized as important emerging
      vector-borne infections in humans. Rickettsial diseases are transmitted by
      different types of arthropods, ticks, fleas, lice, and mites. This review will
      examine the roles of these different arthropod vectors and their geographical
      distributions.

PMID- 23168052
TI  - Features of Brazilian spotted fever in two different endemic areas in Brazil.
AB  - Brazilian spotted fever (BSF) caused by Rickettsia rickettsii is the most
      important rickettsiosis and the only reportable tick-borne disease in Brazil. In
      Brazil, the hard tick Amblyomma cajennense is the most important BSF vector;
      however, in Sao Paulo State, A. aureolatum was also recognized as a vector
      species in remaining Atlantic forest areas near the metropolitan area of Sao
      Paulo city. We analyzed clinical and epidemiological features of BSF cases from
      two distinct areas where A. cajennense (Area 1) and A. aureolatum (Area 2) are
      the incriminated vectors. The clinical features demonstrate the same severity
      pattern of BSF in both endemic areas. Differences in seasonality, patient
      characteristics (median age and gender), and epidemiological risk factors
      (animals host contact and vegetation characteristics) were observed and possibly
      could be attributed to the characteristics of each vector and their typical
      biological cycle (hosts and environment).

PMID- 23168054
TI  - Spotted fever group rickettsiae identified in Dermacentor marginatus and Ixodes
      ricinus ticks in Algeria.
AB  - Our study was carried out using Ixodes ricinus ticks collected from cattle from
      Tizi-Ouzou and Dermacentor marginatus ticks collected from the vegetation of the
      Blida region, a tourist site, both regions situated in northern Algeria. The
      results of real-time quantitative PCR (qPCR) specific for a partial sequence of
      the citrate synthase gene (gltA) indicate that Rickettsia spp. were present in
      11/23 (48%) and 4/9 (44%) of the examined ticks from Tizi-Ouzou and Blida,
      respectively. The sequences of Rickettsia helvetica and Ri. monacensis were found
      in I. ricinus ticks using gltA primers. In addition, Ri. slovaca was detected
      based on the sequences of the gltA and the outer membrane protein (OmpA) genes in
      D. marginatus ticks. DNA sequencing to identify the species revealed for the
      first time the presence of Ri. helvetica in I. ricinus ticks and Ri. slovaca in
      D. marginatus ticks from Algeria and confirmed the presence of Ri. monacensis.

PMID- 23168055
TI  - The first molecular detection of Rickettsia aeschlimannii in the ticks of camels
      from southern Algeria.
AB  - We collected ticks from camels in 4 regions of southern Algeria (El Oued, Bechar,
      Ghardia, and Adrar) from February to October in 2008 and in April of 2011. A
      total of 307 ticks representing multiple species (including Hyalomma dromedarii,
      H. marginatum rufipes, H. impeltatum, and H. impressum), was tested for the
      presence of spotted fever group rickettsia DNA using gltA real-time quantitative
      PCR (qPCR). The presence of Rickettsia aeschlimannii was confirmed with a new
      qPCR using species-specific primers and Taqman probes based on the sca2 genes.
      The R. aeschlimannii sequence was further confirmed by detecting the gltA and
      outer membrane protein (ompA) genes in H. m. rufipes, H. impeltatum, and H.
      dromedarii ticks. These findings represent the first report of the detection of
      R. aeschlimannii in ticks collected from camels from southern Algeria.

PMID- 23168056
TI  - Effect of pre-freeze semen quality, extender and cryoprotectant on the post-thaw
      quality of Asian elephant (Elephas maximus indicus) semen.
AB  - Semen cryopreservation and artificial insemination (AI) are potentially valuable
      methods for supporting the breeding management of endangered species like the
      Asian elephant. Cryopreservation of Asian elephant semen has however proven
      problematic with respect to maintenance of both adequate semen quality and
      fertility post-thaw. In this study, nine ejaculates from three adult bulls were
      used to compare the influence of extender (TEST versus INRA96(r)) and penetrating
      cryoprotectants (3% glycerol, 5% glycerol and 4% methylformamide) on post-thaw
      semen quality. We demonstrate that not only the freezing process, but also the
      quality of the semen before freezing, significantly influences the freezability
      of Asian elephant semen. Pre-freeze motility, viability, semen volume, semen pH,
      sperm concentration and the incidence of sperm mid-piece and tail abnormalities
      all significantly (p<0.05) affected post-thaw semen quality. While extender and
      cryoprotectant did not significantly affect any of the above semen quality
      parameters post-thaw, the skim-milk based extender (INRA96(r)) preserved DNA
      integrity better (p<0.05) than the egg yolk extender (TEST). Considerable between
      ejaculate variation in all post-thaw semen quality parameters was also noted. It
      is concluded that strict criteria for semen quality is essential for the
      selection of Asian elephant bull ejaculates suitable for cryopreservation;
      stricter initial selection should improve the mean post-thaw quality.

PMID- 23168057
TI  - Biological assessment of abnormal genitalia.
AB  - Biological assessment of abnormal genitalia is based on an ordered sequence of
      endocrine and genetic investigations that are predicated on knowledge obtained
      from a suitable history and detailed examination of the external genital anatomy.
      Investigations are particularly relevant in 46,XY DSD where the diagnostic yield
      is less successful than in the 46,XX counterpart. Advantage should be taken of
      spontaneous activity of the pituitary-gonadal axis in early infancy rendering
      measurements of gonadotrophins and sex steroids by sensitive, validated assays
      key to assessing testicular function. Allied measurement of serum anti-Mullerian
      hormone completes a comprehensive testis profile of Leydig and Sertoli cell
      function. Genetic assessment is dominated by analysis of a plethora of genes that
      attempts to delineate a cause for gonadal dysgenesis. In essence, this is
      successful in up to 20% of cases from analysis of SRY and SF1 (NR5A1) genes. In
      contrast, gene mutation analysis is highly successful in 46,XY DSD due to defects
      in androgen synthesis or action. The era of next generation sequencing is
      increasingly being applied to investigate complex medical conditions of unknown
      cause, including DSD. The challenge for health professionals will lie in
      integrating vast amounts of genetic information with phenotypes and counselling
      families appropriately. How tissues respond to hormones is apposite to assessing
      the range of genital phenotypes that characterise DSD, particularly for syndromes
      associated with androgen resistance. In vitro methods are available to undertake
      quantitative and qualitative analysis of hormone action. The in vivo equivalent
      is some assessment of the degree of under-masculinisation in the male, such as an
      external masculinisation score, and measurement of the ano-genital distance. This
      anthropometric marker is effectively a postnatal readout of the effects of
      prenatal androgens acting during the masculinisation programming window. For
      investigation of the newborn with abnormal genitalia, a pragmatic approach can be
      taken to guide the clinician using appropriate algorithms.

PMID- 23168058
TI  - Letter from the editor: the pulmonary vasculature.

PMID- 23168059
TI  - Pulmonary circulation imaging: embryology and normal anatomy.
AB  - This review focuses on the embryology and normal imaging anatomy of the pulmonary
      circulation, with emphasis on the major arterial and venous vasculature. The
      pulmonary circulation and parenchyma have a complex intertwined embryologic
      origin. Understanding the embryologic basis of normal pulmonary vasculature aids
      recognition of anomalies and visceral situs in the chest. Adaptive changes to
      congenital anomalies of the pulmonary arterial vasculature are used to contrast
      from normal and review associated temporal adaptive vascular and parenchymal
      changes.

PMID- 23168060
TI  - Anomalous pulmonary venous connections.
AB  - Developmental lung anomalies are classified into 3 main categories:
      bronchopulmonary (lung bud) anomalies, vascular anomalies, and combined lung and
      vascular anomalies. These anomalies are uncommon, and patients are at times
      asymptomatic; hence, identifying a developmental lung anomaly in the adult can be
      a challenge. Pulmonary vascular anomalies include interruption or absence of the
      main pulmonary artery, anomalous origin of the left pulmonary artery from the
      right pulmonary artery, anomalous pulmonary venous drainage (partial or
      complete), and pulmonary arteriovenous malformations. Systemic vascular anomalies
      comprise persistent left superior vena cava, anomalies of azygos and hemiazygos
      systems, and anomalies of the thoracic aorta and its major branches. In this
      article, we present embryology, classification, epidemiology, clinical
      presentation, and imaging features of anomalous pulmonary venous connections,
      with special emphasis on multidetector computed tomography and magnetic resonance
      imaging. These state-of-art imaging techniques have facilitated accurate and
      prompt diagnosis of these anomalies.

PMID- 23168061
TI  - Acute and chronic pulmonary embolism: an in-depth review for radiologists through
      the use of frequently asked questions.
AB  - In this article, the authors review the role of the different imaging modalities
      in the diagnostic workup of patients with suspected acute or chronic pulmonary
      embolism (PE). The authors also discuss the current guidelines for the diagnosis
      of acute PE based on the pretest probability clinical assessment and outline the
      current recommendations for special patient populations. The recent guidelines
      from the American Thoracic Society/Society of Thoracic Radiology for the
      assessment of suspected PE in pregnancy are also reviewed. Finally, the imaging
      findings in acute and chronic PE are illustrated.

PMID- 23168062
TI  - Nonthrombotic pulmonary embolism: a radiological perspective.
AB  - In this review, the authors highlight the clinical setting, symptoms, and imaging
      findings in nonthrombotic pulmonary embolism that radiologists may encounter in
      their clinical practice. We illustrate the imaging features based on the inciting
      agent with an emphasis on computed tomography. The diagnosis of nonthrombotic
      pulmonary embolism usually requires a high index of clinical suspicion and
      knowledge of the typical radiological findings.

PMID- 23168063
TI  - The imaging of pulmonary hypertension.
AB  - Pulmonary hypertension (PH) is the remarkable hemodynamic consequence of
      widespread structural and functional changes within the pulmonary circulation.
      Elevated pulmonary vascular resistance leads to increased mean pulmonary arterial
      pressure and, ultimately, right ventricular dysfunction. PH carries a poor
      prognosis and warrants timely and accurate diagnosis for appropriate
      intervention. The 2008 Dana Point classification system provides the categorical
      framework currently guiding therapy and surveillance. Radiologic imaging is an
      essential tool in the detection and diagnostic evaluation of patients with PH.
      Echocardiography, ventilation-perfusion scintigraphy, multidetector computed
      tomography, and cardiac magnetic resonance imaging provide insights into vascular
      morphology, pulmonary parenchymal status, cardiac function, and underlying
      etiology of the disorder. Emerging techniques of functional pulmonary and cardiac
      imaging hold great promise for the assessment and monitoring of these patients in
      the future.

PMID- 23168064
TI  - Aneurysms and pseudoaneurysms of the pulmonary vasculature.
AB  - Aneurysms of the pulmonary vasculature may arise from the pulmonary arteries,
      bronchial arteries, or pulmonary veins. Their pathophysiology and clinical
      presentation are variable depending on the underlying condition, some of which
      have significant morbidity and mortality. Consequently, imaging plays a central
      role in the diagnosis and treatment planning. This review article presents a
      classification of the different types of aneurysms that can affect the pulmonary
      vasculature and reviews the most common conditions associated with them and
      discusses their imaging presentation.

PMID- 23168065
TI  - Imaging findings in pulmonary vasculitis.
AB  - Vasculitis is a destructive inflammatory process affecting blood vessels.
      Pulmonary vasculitis may develop secondary to other conditions or constitute a
      primary idiopathic disorder. Thoracic involvement is most common in primary
      idiopathic large-vessel vasculitides (Takayasu arteritis, giant cell arteritis,
      Behcet disease) and primary antineutrophil cytoplasmic autoantibody-associated
      small-vessel vasculitides (Wegener granulomatosis, microscopic polyangiitis,
      Churg-Strauss syndrome). Primary pulmonary vasculitides are rare, and their signs
      and symptoms are nonspecific, overlapping with those of infections, connective
      tissue diseases, and malignancies. The radiologic findings in primary pulmonary
      vasculitis vary widely and can include vessel wall thickening, nodular or
      cavitary lesions, ground-glass opacities, and consolidations, among others.
      Diffuse alveolar hemorrhage usually results from primary small-vessel vasculitis
      in the lungs. To diagnose vasculitis, medical teams must recognize characteristic
      combinations of clinical, radiologic, laboratory, and histopathologic features.

PMID- 23168066
TI  - Tumors of the pulmonary artery and veins.
AB  - The pulmonary vasculature may be involved by different primary and secondary
      tumors. Poorly differentiated and undifferentiated sarcomas are the most common
      primary tumors of the pulmonary arteries. They tend to affect the large caliber
      pulmonary vessels and present with predominantly intraluminal growth. Pulmonary
      and mediastinal metastasis are common, and prognosis is poor. Clinical and
      imaging manifestations may mimic those of pulmonary embolism. Dyspnea, chest
      pain, cough, and hemoptysis are the most common presenting symptoms. Primary
      sarcomas arising from the central pulmonary veins are less common than their
      arterial counterpart. Secondary involvement of the pulmonary arteries and veins
      by primary and metastatic pulmonary malignancies is more common. Tumoral embolism
      may also affect the pulmonary arteries. They may develop from different
      intrathoracic and extrathoracic malignancies and may be indistinguishable from
      venous thromboembolism. It may manifest as cor pulmonale with right cardiac
      strain and dilated pulmonary arteries. Computed tomography, magnetic resonance
      imaging, and fluorodeoxyglucose positron emission tomography may help in the
      differentiation between these 2 conditions.

PMID- 23168067
TI  - The burden of breast cancer in Italy: mastectomies and quadrantectomies performed
      between 2001 and 2008 based on nationwide hospital discharge records.
AB  - BACKGROUND: Where population coverage is limited, the exclusive use of Cancer
      Registries might limit ascertainment of incident cancer cases. We explored the
      potentials of Nationwide hospital discharge records (NHDRs) to capture incident
      breast cancer cases in Italy. METHODS: We analyzed NHDRs for mastectomies and
      quadrantectomies performed between 2001 and 2008. The average annual percentage
      change (AAPC) and related 95% Confidence Interval (CI) in the actual number of
      mastectomies and quadrantectomies performed during the study period were computed
      for the full sample and for subgroups defined by age, surgical procedure, macro
      area and singular Region. Re-admissions of the same patients were separately
      presented. RESULTS: The overall number of mastectomies decreased, with an AAPC of
      -2.1% (-2.3 -1.8). This result was largely driven by the values observed for
      women in the 45 to 64 and 65 to 74 age subgroups (-3.0%, -3.4 -3.6 and -3.3%, 
      3.8 -2.8, respectively). We observed no significant reduction in mastectomies for
      women in the remaining age groups. Quadrantectomies showed an overall +4.7 AAPC
      (95%CI:4.5-4.9), with no substantial differences by age. Analyses by geographical
      area showed a remarkable decrease in mastectomies, with inter-regional
      discrepancies possibly depending upon variability in mammography screening
      coverage and adherence. Quadrantectomies significantly increased, with Southern
      Regions presenting the highest average rates. Data on repeat admissions within a
      year revealed a total number of 46,610 major breast surgeries between 2001 and
      2008, with an overall +3.2% AAPC (95%CI:2.8-3.6). CONCLUSIONS: In Italy, NHDRs
      might represent a valuable supplemental data source to integrate Cancer
      Registries in cancer surveillance.

PMID- 23168069
TI  - Long term curative effects of sequential therapy with all-trans retinoic acid,
      arsenious oxide and chemotherapy on patients with acute promyelocytic leukemia.
AB  - BACKGROUND: Both all-trans retinoic acid (ATRA) and arsenic trioxide (As(2)O(3))
      have proven to be very effective in obtaining high clinical complete remission
      (CR) rates in acute promyelocytic leukemia (APL). METHODS: In this study, 73 
      newly diagnosed APL subjects were treated with an ATRA and As(2)O(3) combination
      treatment in remission induction and post remission therapy. Tumor burden was
      examined with PCR of the PML-RAR fusion transcripts, and side effects were
      evaluated by means of clinical examination. RESULTS: The results showed that
      ATRA/As(2)O(3) combination therapy yielded a CR rate of 94.5% (69/73) with a
      shorter time to enter CR (median: 27 days; range: 21-43 days). Four cases failed
      to enter CR; three of these died of cerebral hemorrhage  and disseminated
      intravascular coagulation (DIC) within 72 hours of starting induction therapy,
      one older patient died of severe pulmonary infection. The early death rate was
      5.5% (4/73). All 69 cases that obtained CR remained in good clinical remission
      after a follow-up of 35-74 months  (median: 52 months).The drug toxicity profile
      with the use of As(2)O(3) showed mainly hepatotoxicity. Liver dysfunction was
      slight in most cases. There were no severe side effects in long term follow-up.
      CONCLUSION: We conclude that APL patients may  benefit from the use of the
      combination of ATRA and As(2)O(3) in either remission induction or
      consolidation/maintenance.

PMID- 23168068
TI  - Hydrodynamic modulation of pluripotent stem cells.
AB  - Controlled expansion and differentiation of pluripotent stem cells (PSCs) using
      reproducible, high-throughput methods could accelerate stem cell research for
      clinical therapies. Hydrodynamic culture systems for PSCs are increasingly being
      used for high-throughput studies and scale-up purposes; however, hydrodynamic
      cultures expose PSCs to complex physical and chemical environments that include
      spatially and temporally modulated fluid shear stresses and heterogeneous mass
      transport. Furthermore, the effects of fluid flow on PSCs cannot easily be
      attributed to any single environmental parameter since the cellular processes
      regulating self-renewal and differentiation are interconnected and the complex
      physical and chemical parameters associated with fluid flow are thus difficult to
      independently isolate. Regardless of the challenges posed by characterizing fluid
      dynamic properties, hydrodynamic culture systems offer several advantages over
      traditional static culture, including increased mass transfer and reduced cell
      handling. This article discusses the challenges and opportunities of hydrodynamic
      culture environments for the expansion and differentiation of PSCs in
      microfluidic systems and larger-volume suspension bioreactors. Ultimately, an
      improved understanding of the effects of hydrodynamics on the self-renewal and
      differentiation of PSCs could yield improved bioprocessing technologies to attain
      scalable PSC culture strategies that will probably be requisite for the
      development of therapeutic and diagnostic applications. 

PMID- 23168070
TI  - Immunohistological analysis in diagnosis of plasma cell myeloma based on
      cytoplasmic kappa/lambda ratio of CD38-positive plasma cells.
AB  - The accurate determination of cytoplasmic immunoglobulin (cIg) light chain (LC)
      expression is important to differentiate reactive plasmacytosis from a clonal
      plasma cell neoplasm such as plasma cell myeloma (PCM). Through retrospective
      analysis, we studied the cytoplasmic kappa/lambda  ratio of CD38-positive plasma
      cells in the bone marrow from 19 PCM patients and 19 controls. To demonstrate cIg
      LC expression, the bone marrow was immunostained for IgA, IgG, IgM, kappa, and
      lambda. The kappa/lambda ratio was defined as the ratio of the kappa-positive
      cell to the lambda-positive  cell in plasma cells. PCM cells were distinguished
      from normal plasma cells by cut-off levels between 0.59 and 4.0, a sensitivity of
      94.7%, and a specificity of 94.7%. The detection of the cytoplasmic kappa/lambda
      ratio of CD38-positive plasma cells may be a useful tool in the diagnosis of  PCM
      and the correct diagnosis of PCM may be achieved more simply.

PMID- 23168071
TI  - Hemophagocytic lymphohistiocytosis in pregnancy: a case report and review of
      treatment options.
AB  - Hemophagocytic lymphohistiocytosis (HLH) is a rare, life-threatening inflammatory
      disorder characterized by uncontrolled proliferation and activation of
      histiocytes with phagocytosis of normal hematopoietic cells. A 41-year-old woman,
      19 weeks pregnant with twins, and a history of Still's  disease, presented with
      rash, fever, and headache. Laboratory studies revealed transaminitis,
      hyperbilirubinemia, and eventually severe neutropenia as well as elevations in
      ferritin, lactate dehydrogenase, and C-reactive protein. A bone marrow biopsy
      confirmed HLH. She declined standard HLH-treatment  but responded well to high
      dose corticosteroids. Her blood counts remained stable following corticosteroid
      taper, and she delivered healthy twin girls at 30-week gestation. Few cases of
      HLH during pregnancy have been reported. In some cases, the condition has proved
      fatal. Therefore recognizing  signs and symptoms of HLH is essential to avoid
      treatment delay. In our case, high-dose corticosteroids alone were a safe and
      effective therapy for the mother and fetuses resulting in long-term disease
      control.

PMID- 23168072
TI  - BCL11B suppression does not influence CD34(+) cell differentiation and
      proliferation.
AB  - The B-cell chronic lymphocytic leukemia (CLL)/lymphoma 11B (BCL11B) gene plays a
      critical role in T-cell differentiation and proliferation. However, little is
      understood about the role of BCL11B in human hematopoietic stem/progenitor cells.
      Small interfering RNA (siRNA)-mediated  suppression of the BCL11B was shown to
      induce apoptosis in human T-cell acute lymphoblastic leukemia cells. To further
      characterize the role of BCL11B in hematopoietic stem/progenitor cells and assess
      the safety of siRNA-mediated targeted therapy, the in vitro differentiation  and
      proliferation of CD34(+) cells after BCL11B-siRNA935 treatment were studied.
      CD34(+) cells were sorted from three cases of umbilical cord blood by the
      magnetic activated cell sorting technique, and the purity was identified by flow
      cytometry. BCL11B-siRNA935  was delivered into CD34(+) cells by nucleofection and
      the BCL11B expression level was analyzed by quantitative real-time polymerase
      chain reaction. Erythroid burst-forming units (BFU-E), granulocyte/macrophage
      colony-forming units (CFU-GM), and megakaryocyte colony-forming  units (CFU-Meg)
      were assessed using BCL11B-siRNA935-treated CD34(+) cells by the methylcellulose
      semi-solid culture method. The BCL11B expression level in CD34(+) cells was
      significantly lower than that in Molt-4 cells and peripheral blood mononuclear
      cells  from healthy individuals. An approximate one-fold reduction in the BCL11B
      mRNA level was observed 24 hours post-transfection with BCL11B-siRNA935. However,
      there was no significant difference on the colony formation ability of BFU-E, CFU
      GM, and CFU-Meg for CD34(+) cells  between the BCL11B-siRNA935-treated and mock
      transfected groups (P > 0.05). BCL11B suppression by RNA interference had no
      significant influence on the differentiation and proliferation of CD34(+) cells.
      In conclusion, the BCL11B-siRNA935 used  in this study may be safe, and BCL11B
      may be considered a new candidate for targeted gene therapy in T-cell
      malignancies.

PMID- 23168073
TI  - Homozygous FVII deficiencies with different reactivity towards tissue
      thromboplastins of different origin.
AB  - The reagents most frequently used for FVII activity assay are obtained by rabbit
      brain or human placenta. In recent years, human recombinant thromboplastins have
      received great attention. FVII activity in FVII deficiency is usually low,
      regardless of the thromboplastin used. There are  a few exceptions to this rule.
      These are represented by FVII Padua (Arg304Gln), FVII Nagoya (Arg304Trp), and
      FVII (Arg79Gln). In these three instances, clear discrepancies were noted in the
      FVII activity depending on the thromboplastin used. This indicates that at least
      two areas of FVII are  involved in tissue binding, namely an epidermal growth
      factor domain of the light chain (Arg79Gln) and the catalytic domain (Arg304),
      controlled by exons 4 and 8, respectively. Since these three variants are cross
      reactive material positive, namely they are Type 2 defects, all other variants 
      with normal antigen should be investigated by a panel of at least three tissue
      thromboplastins (rabbit brain, human tissue or human recombinant, and ox brain
      derived) in order to obtain a satisfactory classification.

PMID- 23168074
TI  - The prevalence of the platelet glycoprotein VI polymorphisms in patients with
      sticky platelet syndrome and ischemic stroke.
AB  - INTRODUCTION: The aim of the study was to evaluate the genetic variability of the
      GP6 gene in patients with sticky platelet syndrome (SPS), a disorder
      characterized by platelet hyperaggregability, and thus to identify the genetic
      changes of the glycoprotein VI with possible  relation to the platelet
      hyperaggregability. PATIENTS AND METHODS: Seventy-one patients with SPS,
      clinically manifested as ischemic stroke, and 77 controls without SPS and with
      negative personal history of thromboembolic events were involved. SPS was
      diagnosed by platelet  aggregometry (PACKS-4 aggregometer, Helena Laboratories)
      according to the method and criteria described by Mammen and Bick. Seven single
      nucleotide polymorphisms (SNPs) of the GP6 gene (rs1654410, rs1671153, rs1654419,
      rs11669150, rs1613662, rs12610286, and rs1654431) were evaluated with the  use of
      restriction-fragment-length polymorphism analysis. RESULTS: All allele and
      genotype frequencies were comparable between both SPS patients and the control
      group with no statistically significant differences. The haplotype analysis
      showed a higher occurrence of the  one major haplotype (TTGTGA, 0.228 vs. 0.174;
      odds ratio (OR) 1.421; confidence interval (CI) 0.799-2.526) and two minor
      haplotypes (CGATAA, 0,026 vs. 0,006; OR 4.117; CI 0.443-38.25; TTGTGG, 0.018 vs.
      0.009; OR 2.107; CI 0.259-17.12) in patients with SPS. None of haplotype 
      differences was statistically significant. However, both the allele G of SNP
      rs12610286 (P = 0.029; OR 2.411; CI 1.134-5.123) and one major haplotype (TTGTGA;
      P = 0.012; OR 2.749; CI 1.223-6.174) were found significantly more frequent in
      patients  with SPS type I in comparison with controls. CONCLUSION: Our results,
      especially higher occurrence of four haplotypes in SPS patients, can support an
      idea that variability of the GP6 gene may be associated with the platelet
      hyperaggregability in SPS.

PMID- 23168075
TI  - Chronic immune thrombocytopenic purpura in childhood: pathogenetic mechanisms and
      management.
AB  - A population of 26 children of both sexes mean age 8.5 +/- 5.8 years with
      thrombocytopaenic purpura, disease duration at least 7 months (2.5 +/- 1.8
      years), platelet count 22 000 +/- 12 000/mm(3) was studied. Patients were 
      divided into three age groups; I: 2-6 years (8 children); II: 7-10 years (10
      children); III: 11-16 years (8 patients). Careful history, physical examination,
      complete blood count with blood smear, platelet autoantibodies, bone marrow
      aspirate, and response to intravenous  immunoglobulins (IV Igs) were evaluated.
      Statistical analysis was performed by chi(2) test. Platelet count, duration of
      disease, megakaryocytic reduction, need of splenectomy were significantly lower
      in younger children than older children of III group (P < 0.05).  All patients
      were responsive to IV Ig. No significant differences of presence of platelet
      autoantibodies, were found among the groups. Relapse after splenectomy was
      observed in four older patients among whom three had Evans syndrome: complete
      remission was obtained with rituximab. Disease  duration appears to be associated
      to megakaryocytic alterations and patient age.

PMID- 23168076
TI  - Iranian experience of deferasirox (Exjade((r))) in transfusion-dependent patients
      with iron overload: what is the most effective dose based on serum ferritin
      levels?
AB  - BACKGROUND: The aim of this study was to evaluate the efficacy and safety of
      deferasirox in patients from Iran. METHODS: This was a retrospective,
      observational study in regularly transfused, iron-overloaded patients who
      received deferasirox 20-38 mg/kg/day  for up to 12 months. Changes in serum
      ferritin were assessed as follows: from baseline to 3 months with deferasirox
      doses of 20-24 mg/kg/day; from 3 to 6 months with doses of 25-29 mg/kg/day; and
      from 6 to 12 months with doses of 30-38 mg/kg/day. The safety  of deferasirox was
      evaluated monthly. Patients' satisfaction with treatment was assessed after 9
      months. RESULTS: One hundred and nineteen patients were included. Overall mean
      serum ferritin levels were significantly decreased from baseline after 12 months
      of deferasirox  therapy (2510 +/- 1210 to 1665 +/- 1240 ng/ml; P < 0.002). A
      significant decrease was observed once doses were increased to >=30 mg/kg/day (P
      = 0.0003). Most adverse events were mild and observed at the dose of  20-24
      mg/kg. Only one patient discontinued treatment. Around 90% of patients were
      satisfied with therapy. CONCLUSION: This is the first study evaluating
      deferasirox in heavily iron-overloaded patients from Iran and confirms that
      deferasirox is effective and well  tolerated; however, dose increases to >=30
      mg/kg/day should be considered if efficacy is insufficient.

PMID- 23168077
TI  - Two sugar isomers influence host plant acceptance by a cereal caterpillar pest.
AB  - Plant sugars are often considered as primary feeding stimuli, conditioning host
      plant acceptance by herbivorous insects. Of the nine sugars identified from
      methanolic extracts of seven grass species, only turanose, a sucrose isomer, was
      negatively correlated with the survival and growth of the noctuid larva of cereal
      stemborer, Busseola fusca. Sucrose was the most abundant sugar, although it did
      not vary significantly in concentration among the plant species studied. Using
      StyrofoamTM cylinders impregnated with increasing concentrations of turanose or
      sucrose, the two sugars had opposing effects: turanose appeared phagodeterrent
      while sucrose was phagostimulatory. Electrophysiological studies indicated that
      B. fusca larvae were able to detect both sugars via their styloconic sensilla
      located on the mouthparts. The findings indicate that, whereas sucrose is a
      feeding stimulant and positively influences food choice by B. fusca larvae,
      turanose negatively contributes to larval food choice. The balance in
      concentrations of both sugars, however, somehow influences the overall host plant
      choice made by the larvae. This can partly explain host plant suitability and
      choice by this caterpillar pest in the field.

PMID- 23168078
TI  - Ultrasound field distribution and ultrasonic oxidation desulfurization
      efficiency.
AB  - Ultrasonic oxidation desulfurization (UODS) has been considered a promising
      method for deeply desulfurization technology since it can be carried out using
      mild conditions. During the last few decades many experimental investigations
      have been carried out on optimizing the reaction condition such as ultrasonic
      irradiation time, oxidizing reagents amount, kind of organic acid and so on. But
      limited work has been reported on the influence of the ultrasonic cavitation
      field distribution. In this work, the relative intensity of the cavitation events
      has been measured with the aluminum foil erosion method in a commonly used
      ultrasonic cleaning vessel both in horizontal and vertical directions. The
      aluminum foil erosion image was then collected into computer by a scanner. In
      addition, the image processing program of MATLAB software was used to pretreat
      the erosion image and find out the positions of the erosion points so that the
      ratio of the erosion area to the entire area can be calculated which helped to
      quantify the measurement result since the erosion ratios was the representation
      of the cavitation intensity. The desulfurization efficiency was then measured in
      different position of the vessel. The results match well with the cavitation
      field distribution results which indicate that the cavitation field distribution
      can be used to guide the UODS process.

PMID- 23168079
TI  - Which acetylcholinesterase functions as the main catalytic enzyme in the Class
      Insecta?
AB  - Most insects possess two different acetylcholinesterases (AChEs) (i.e., AChE1 and
      AChE2; encoded by ace1 and ace2 genes, respectively). Between the two AChEs,
      AChE1 has been proposed as a major catalytic enzyme based on its higher
      expression level and frequently observed point mutations associated with
      insecticide resistance. To investigate the evolutionary distribution of AChE1 and
      AChE2, we determined which AChE had a central catalytic function in several
      insect species across 18 orders. The main catalytic activity in heads was
      determined by native polyacrylamide gel electrophoresis in conjunction with
      Western blotting using AChE1- and AChE2-specific antibodies. Of the 100 insect
      species examined, 67 species showed higher AChE1 activity; thus, AChE1 was
      considered as the main catalytic enzyme. In the remaining 33 species, ranging
      from Palaeoptera to Hymenoptera, however, AChE2 was predominantly expressed as
      the main catalytic enzyme. These findings challenge the common notion that AChE1
      is the only main catalytic enzyme in insects with the exception of Cyclorrhapha,
      and further demonstrate that the specialization of AChE2 as the main enzyme or
      the replacement of AChE1 function with AChE2 were rather common events, having
      multiple independent origins during insect evolution. It was hypothesized that
      the generation of multiple AChE2 isoforms by alternative splicing allowed the
      loss of ace1 during the process of functional replacement of AChE1 with AChE2 in
      Cyclorrhapha. However, the presence of AChE2 as the main catalytic enzyme in
      higher social Hymenoptera provides a case for the functional replacement of AChE1
      with AChE2 without the loss of ace1. The current study will provide valuable
      insights into the evolution of AChE: which AChE has been specialized as the main
      catalytic enzyme and to become the main target for insecticides in different
      insect species.

PMID- 23168080
TI  - Synthesis and characterization of a small analogue of the anticancer natural
      product leinamycin.
AB  - Leinamycin (1) is a Streptomyces-derived natural product that displays nanomolar
      IC(50) values against human cancer cell lines. In the work described here, we
      report the synthesis and characterization of a small leinamycin analogue 19 that
      closely resembles the 'upper-right quadrant' of the natural product, consisting
      of an alicyclic 1,2-dithiolan-3-one 1-oxide heterocycle connected to an alkene by
      a two-carbon linker. The results indicate that this small analogue contains the
      core set of functional groups required to enable thiol-triggered generation of
      both redox active polysulfides and an episulfonium ion intermediate via the
      complex reaction cascade first seen in the natural product leinamycin. The small
      leinamycin analogue 19 caused thiol-triggered oxidative DNA strand cleavage in a
      manner similar to the natural product, but did not alkyate duplex DNA
      effectively. This highlights the central role of the 18-membered macrocycle of
      leinamycin in driving efficient DNA alkylation by the natural product.

PMID- 23168081
TI  - New selective carbonic anhydrase IX inhibitors: synthesis and pharmacological
      evaluation of diarylpyrazole-benzenesulfonamides.
AB  - Carbonic anhydrase (CA) IX expression is increased upon hypoxia and has been
      proposed as a therapeutic target since it has been associated with poor
      prognosis, tumor progression and pH regulation. We report the synthesis and the
      pharmacological evaluation of a new class of human carbonic anhydrase (hCA)
      inhibitors, 4-(5-aryl-2-hydroxymethyl-pyrazol-1-yl)-benzenesulfonamides. A
      molecular modeling study was conducted in order to simulate the binding mode of
      this new family of enzyme inhibitors within the active site of hCA IX.
      Pharmacological studies revealed high hCA IX inhibitory potency in the parameters
      nanomolar range. This study showed that the position of sulfonamide group in meta
      of the 1-phenylpyrazole increase a selectivity hCA IX versus hCA II of our
      compounds. An in vitro antiproliferative screening has been performed on the
      breast cancer MDA-MB-231 cell using doxorubicin as cytotoxic agent and in
      presence of selected CA IX inhibitor. The results shown that the cytotoxic
      efficiency of doxorubicin in an hypoxic environment, expressed in IC50 value, is
      restored at 20% level with 1MUM CA IX inhibitor.

PMID- 23168082
TI  - Synthesis, characterization and antimalarial activity of quinoline-pyrimidine
      hybrids.
AB  - The aim of this study was to synthesize a series of quinoline-pyrimidine hybrids
      and to evaluate their in vitro antimalarial activity as well as cytotoxicity. The
      hybrids were brought about in a two-step nucleophilic substitution process
      involving quinoline and pyrimidine moieties. They were screened alongside
      chloroquine (CQ), pyrimethamine (PM) and fixed combinations thereof against the
      D10 and Dd2 strains of Plasmodium falciparum. The cytotoxicity was determined
      against the mammalian Chinese Hamster Ovarian cell line. The compounds were all
      active against both strains. However, hybrid (21) featuring piperazine linker
      stood as the most active of all. It was found as potent as CQ and PM against the
      D10 strain, and possessed a moderately superior potency over CQ against the Dd2
      strain (IC(50): 0.157 vs 0.417 MUM, ~threefold), and also displayed activity
      comparable to that of the equimolar fixed combination of CQ and PM against both
      strains.

PMID- 23168083
TI  - The role of executive attention in the acquisition of mathematical skills for
      children in Grades 2 through 4.
AB  - We examined the role of executive attention, which encompasses the common aspects
      of executive function and executive working memory, in children's acquisition of
      two aspects of mathematical skill: (a) knowledge of the number system (e.g.,
      place value) and of arithmetic procedures (e.g., multi-digit addition) and (b)
      arithmetic fluency (i.e., speed of solutions to simple equations such as 3+4 and
      8-5). Children in Grades 2 and 3 (N=157) completed executive attention and
      mathematical tasks. They repeated the mathematical tasks 1 year later. We used
      structural equation modeling to examine the relations between executive attention
      and (a) concurrent measures of mathematical knowledge and arithmetic fluency and
      (b) growth in performance on these measures 1 year later. Executive attention was
      concurrently predictive of both knowledge and fluency but predicted growth in
      performance only for fluency. A composite language measure predicted growth in
      knowledge from Grade 2 to Grade 3. The results support an important role for
      executive attention in children's acquisition of novel procedures and the
      development of automatic access to arithmetic facts.

PMID- 23168084
TI  - Neurosteroidogenic enzymes and their regulation in the early brain of the
      protogynous grouper Epinephelus coioides during gonadal sex differentiation.
AB  - The regulatory role of neurosteroids in the early brain during gonadal sex
      differentiation is unclear. The aim of this study was to investigate the
      expression and cellular localization of key steroidogenic enzymes in the early
      brain of the protogynous orange-spotted grouper Epinephelus coioides and the
      temporal expressions has been correlated with gonadal sex differentiation. In
      this study, we showed that peak neurosteroidogenesis occurs in the early brain
      during gonadal sex differentiation. The temporal expressions of key enzymes,
      cyp11a1 (cytochrome P450 side chain cleavage), hsd3b1 (3beta-hydroxysteroid
      dehydrogenase) and cyp17a1 (cytochrome P450c17) were studied at different
      developmental ages (from 90- to 150-dah: days after hatching) using quantitative
      real-time PCR (q-PCR). q-PCR analysis indicated that the transcript expressions
      of cyp11a1, hsd3b1 and cyp17a1 were increased in the brain around the period of
      gonadal sex differentiation. Further, in situ hybridization (ISH) analysis showed
      that cyp11a1, hsd3b1 and cyp17a1 transcripts were widely expressed in several
      discrete brain regions, especially the intense expression in the forebrain, with
      an overall similar expression pattern. High density in the cyp19a1b/Cyp19a1b
      expression was detected in radial glial cells. Thus, the expression of grouper
      cyp19a1b/Cyp19a1b is restricted to radial glial cells, suggesting estrogens can
      modulate their activity. Next, by combining Cyp19a1b immunohistochemistry (IHC)
      with florescence ISH (FISH) of cyp11a1, hsd3b1 and cyp17a1, we showed that sub
      cellular localization of cyp11a1, hsd3b1 and cyp17a1 transcripts, in partial,
      appeared to be in Cyp19a1b radial glial cell soma. Further, exogenous estradiol
      (E(2)) increased the expression of cyp17a1 and cyp19a1b/Cyp19a1b in the brain of
      grouper. Consequently, our results illustrated that the locally synthesized E(2)
      upregulated neurosteroidogenic enzymes in the early brain and suggest a role for
      these enzymes in the neurogenic process during gonadal sex differentiation.

PMID- 23168085
TI  - Female preference for males depends on reproductive physiology in the African
      cichlid fish Astatotilapia burtoni.
AB  - Mate choice is fundamental to sexual selection, yet little is known about
      underlying physiological mechanisms that influence female mating decisions. We
      investigated the endocrine underpinnings of female mate choice in the African
      cichlid Astatotilapia burtoni, a non-seasonal breeder. In addition to profiling
      behavioral and hormonal changes across the female reproductive cycle, we tested
      two hypotheses regarding possible factors influencing female mate choice. We
      first asked whether female mate choice is influenced by male visual and/or
      chemical cues. A. burtoni females were housed for one full reproductive cycle in
      the center of a dichotomous choice apparatus with a large (attractive) or small
      (unattractive) conspecific male on either side. Females associated mostly with
      small, less attractive males, but on the day of spawning reversed their
      preference to large, attractive males, with whom they mated almost exclusively,
      although this choice depended on the relative amount of androgens released into
      the water by small males. We next asked whether male behavior or androgen levels
      change in relation to the stimulus females' reproductive state. We found that
      stimulus male aggression decreased and reproductive displays increased as the day
      of spawning approached. Moreover male testosterone levels changed throughout the
      females' reproductive cycle, with larger males releasing more testosterone into
      the water than small males. Our data suggest that female association in a
      dichotomous choice assay is only indicative of the actual mate choice on the day
      of spawning. Furthermore, we show that male behavior and hormone levels are
      dependent on the reproductive state of conspecific females.

PMID- 23168086
TI  - Interrelation between melanocyte-stimulating hormone and melanin-concentrating
      hormone in physiological body color change: roles emerging from barfin flounder
      Verasper moseri.
AB  - In teleosts, as their names suggest, the main target cells of melanocyte
      stimulating hormone (MSH) and melanin-concentrating hormone (MCH) are the
      chromatophores in the skin, where these peptide hormones play opposing roles in
      regulating pigment migration. These effects are obvious especially when their
      activities are examined in vitro. On the contrary, while MCH also exhibits
      activity in vivo, MSH does not always stimulate pigment dispersion in vivo
      because of predominant sympathetic nervous system. A series of our investigations
      indicates that this is also the case in barfin flounder, Verasper moseri.
      Interestingly, we observed that mch expression and the tissue contents of MCH can
      be easily influenced by changes in environmental color conditions, while gene
      expression and tissue contents related to MSH scarcely respond to color changes.
      Transcripts of MSH and MCH receptor genes have been identified in a variety of
      tissues of this fish species, suggesting that these are multifunctional peptide
      hormones. Nevertheless, chromatophores in the skin still offer important clues in
      the efforts to elucidate the functions of melanotropic peptides. Herein, we
      review the most recent advancements of our studies on MSH and MCH and their
      receptors in the barfin flounder and discuss the interrelations between these
      peptides, focusing on their roles in influencing pigment migration in the skin.

PMID- 23168087
TI  - Adrenaline and triiodothyronine modify the iron handling in the freshwater air
      breathing fish Anabas testudineus Bloch: role of ferric reductase in iron
      acquisition.
AB  - The effects of in vivo adrenaline and triiodothyronine (T(3)) on ferric reductase
      (FR) activity, a membrane-bound enzyme that reduces Fe(III) to Fe(II) iron, were
      studied in the organs of climbing perch (Anabas testudineus Bloch). Adrenaline
      injection (10 ng g(-1)) for 30 min produced significant inhibition of FR activity
      in the liver and kidney and that suggests a role for this stress hormone in iron
      acquisition in this fish. Short-term T(3) injection (40 ng g(-1)) reduced FR
      activity in the gills of fed fish but not in the unfed fish. Similar reduction of
      FR activity was also obtained in the intestine and kidney of fed fish after T(3)
      injection. Feeding produced pronounced decline in FR activity in the spleen but
      T(3) challenge in fed and unfed fish increased its activity in this iron storing
      organ and that point to the sensitivity of FR system to feeding activity. The in
      vitro effects of Fe on FR activity in the gill explants of freshwater fish showed
      correlations of FR with Na(+), K(+)-ATPase and H(+)-ATPase activities.
      Substantial increase in the FR activity was found in the gill explants incubated
      with all the tested doses of Fe(II) iron (1.80, 3.59 and 7.18 MUM) and Fe(III)
      iron (1.25, 2.51 and 5.02 MUM) and this indicate that FR and Na pump activity are
      positively correlated. On the contrary, substantial reduction of gill H(+)-ATPase
      activity was found in the gill explants incubated with Fe(II) iron and Fe(III)
      iron indicating that perch gills may not require a high acidic microenvironment
      for the reduction of Fe(III) iron. Accumulation of iron in the gill explants
      after Fe(III) iron incubation implies a direct relationship between Fe
      acquisition and FR activity in this tissue. The inverse correlation between FR
      activity and H(+)-ATPase activity in Fe(II) or Fe(III) loaded gills and the
      significant positive correlations of FR activity with total [Fe] content in the
      Fe(III) loaded gills substantiate that FR which shows sensitivity to sodium and
      proton pumps, has a vital role in Fe(II) and Fe(III) iron handling in this fish.
      Our data also provide evidence that adrenaline, T(3) and the feeding status are
      the vital factors that can regulate the storage and handling of iron in fish.

PMID- 23168088
TI  - Enucleation of pancreatic lesions through laparotomy.

PMID- 23168089
TI  - Short-term outcome of psychogenic non-epileptic seizures after communication of
      the diagnosis.
AB  - We previously described a communication strategy for the delivery of the
      diagnosis of psychogenic non-epileptic seizures (PNES) that was acceptable and
      effective at communicating the psychological cause of PNES. This prospective
      multicenter study describes the short-term seizure and psychosocial outcomes
      after the communication of the diagnosis and with no additional treatment.
      Participants completed self-report measures at baseline, two and six months after
      the diagnosis (seizure frequency, HRQoL, health care utilization, activity
      levels, symptom attributions and levels of functioning). Thirty-six participants
      completed the self-report questionnaires. A further eight provided seizure
      frequency data. After six months, the median seizure frequency had dropped from
      10 to 7.5 per month (p=0.9), 7/44 participants (16%) were seizure-free, and an
      additional 10/44 (23%) showed greater than 50% improvement in seizure frequency.
      Baseline questionnaire measures demonstrated high levels of impairment, which had
      not improved at follow-up. The lack of change in self-report measures illustrates
      the need for further interventions in this patient group.

PMID- 23168090
TI  - Psychogenic seizures and psychogenic movement disorders: are they the same
      patients?
AB  - Psychogenic nonepileptic seizures (PNES) and psychogenic movement disorders (PMD)
      are common and disabling problems with abnormal psychological profiles, and they
      may have common features that could aid in better understanding and management.
      Since PNES and PMD are investigated and reported separately, comparisons are
      lacking. Psychogenic nonepileptic seizure and psychogenic movement disorder
      patients completed demographic, clinical, and psychological inventories including
      the Short Form (SF)-12 Health Status Survey (Physical and Mental Health Summary
      Scores), the Brief Symptom Inventory (BSI)-18 (somatization, depression, and
      anxiety subscales), and the Lorig Self-Efficacy Scale. Psychogenic nonepileptic
      seizure and psychogenic movement disorder patients had similar psychological
      profiles with reduced SF-12 Physical Health and Mental Health Summary Scores and
      increased BSI somatization, depression, and anxiety ratings. They varied slightly
      in age and gender, but their main distinguishing features were the presenting
      signs. These similar profiles suggest that PNES and PMD may not be distinct or
      separate entities and that collaborative investigative efforts and management are
      warranted.

PMID- 23168091
TI  - Chemokine Ligand 5 (CCL5) and chemokine receptor (CCR5) genetic variants and
      prostate cancer risk among men of African Descent:  a case-control study.
AB  - BACKGROUND: Chemokine and chemokine receptors play an essential role in
      tumorigenesis. Although chemokine-associated single nucleotide polymorphisms
      (SNPs) are associated with various cancers, their impact on prostate cancer (PCA)
      among men of African descent is unknown. Consequently, this study evaluated 43
      chemokine-associated SNPs in relation to PCA risk. We hypothesized inheritance of
      variant chemokine-associated alleles may lead to alterations in PCA
      susceptibility, presumably due to variations in antitumor immune responses.
      METHODS: Sequence variants were evaluated in germ-line DNA samples from 814
      African-American and Jamaican men (279 PCA cases and 535 controls) using
      Illumina's Goldengate genotyping system. RESULTS: Inheritance of CCL5 rs2107538
      (AA, GA+AA) and rs3817655 (AA, AG, AG+AA) genotypes were linked with a 34-48%
      reduction in PCA risk. Additionally, the recessive and dominant models for CCR5
      rs1799988 and CCR7 rs3136685 were associated with a 1.52-1.73 fold increase in
      PCA risk. Upon stratification, only CCL5 rs3817655 and CCR7 rs3136685 remained
      significant for the Jamaican and U.S. subgroups, respectively. CONCLUSIONS: In
      summary, CCL5 (rs2107538, rs3817655) and CCR5 (rs1799988) sequence variants
      significantly modified PCA susceptibility among men of African descent, even
      after adjusting for age and multiple comparisons. Our findings are only
      suggestive and require further evaluation and validation in relation to prostate
      cancer risk and ultimately disease progression, biochemical/disease recurrence
      and mortality in larger high-risk subgroups. Such efforts will help to identify
      genetic markers capable of explaining disproportionately high prostate cancer
      incidence, mortality, and morbidity rates among men of African descent.

PMID- 23168092
TI  - From cytogenomic to epigenomic profiles: monitoring the biologic behavior of in
      vitro cultured human bone marrow mesenchymal stem cells.
AB  - INTRODUCTION: Bone marrow mesenchymal stem cells (BM-MSCs) are multipotent cells
      that can differentiate into different cell lineages and have emerged as a
      promising tool for cell-targeted therapies and tissue engineering. Their use in a
      therapeutic context requires large-scale in vitro expansion, increasing the
      probability of genetic and epigenetic instabilities. Some evidence shows that an
      organized program of replicative senescence is triggered in human BM-MSCs (hBM
      MSCs) on prolonged in vitro expansion that includes alterations in phenotype,
      differentiation potential, telomere length, proliferation rates, global gene
      expression patterns, and DNA methylation profiles. METHODS: In this study, we
      monitored the chromosomal status, the biologic behavior, and the senescence state
      of hBM-MSCs derived from eight healthy donors at different passages during in
      vitro propagation. For a more complete picture, the telomere length was also
      monitored in five of eight donors, whereas the genomic profile was evaluated in
      three of eight donors by array-comparative genomic hybridization (array-CGH).
      Finally, an epigenomic profile was delineated and compared between early and late
      passages, by pooling DNA of hBM-MSCs from four donors. RESULTS: Our data indicate
      that long-term culture severely affects the characteristics of hBM-MSCs. All the
      observed changes (that is, enlarged morphology, decreased number of cell
      divisions, random loss of genomic regions, telomere shortening) might be
      regulated by epigenetic modifications. Gene Ontology analysis revealed that
      specific biologic processes of hBM-MSCs are affected by variations in DNA
      methylation from early to late passages. CONCLUSIONS: Because we revealed a
      significant decrease in DNA methylation levels in hBM-MSCs during long-term
      culture, it is very important to unravel how these modifications can influence
      the biologic features of hBM-MSCs to keep track of this organized program and
      also to clarify the conflicting observations on hBM-MSC malignant transformation
      in the literature.

PMID- 23168093
TI  - Reproductive preferences and contraceptive use: a comparison of monogamous and
      polygamous couples in northern Malawi.
AB  - There is now widespread agreement on the importance of men's role in reproductive
      decision-making. Several studies have argued that fertility preferences and their
      translation into behaviour differ between polygamous and monogamous unions.
      Studies investigating the dominance of men's preferences over women's
      preferences, in cases of couple disagreement, found mixed evidence of the effect
      of polygamy. However, an often cited limitation of these studies has been the
      inability to link husband's intention with each of his wives in a polygamous
      union. By adding fertility-intention questions to an on-going Demographic
      Surveillance Site in Karonga District in northern Malawi the fertility
      preferences and contraceptive use of husbands and wives were investigated. An
      analysis of the relationship between the level of agreement and disagreement
      between husbands' and wives' fertility preferences was then performed to gain
      insight into the reproductive decision-making process of polygamous couples.

PMID- 23168094
TI  - Periplasmic production via the pET expression system of soluble, bioactive human
      growth hormone.
AB  - A pET based expression system for the production of recombinant human growth
      hormone (hGH) directed to the Escherichia coli periplasmic space was developed.
      The pET22b plasmid was used as a template for creating vectors that encode hGH
      fused to either a pelB or ompA secretion signal under control of the strong
      bacteriophage T7 promoter. The pelB- and ompA-hGH constructs expressed in BL21
      (lambdaDE3)-RIPL E. coli are secreted into the periplasm which facilitates
      isolation of soluble hGH by selective disruption of the outer membrane. A carboxy
      terminal poly-histidine tag enabled purification by Ni(2+) affinity
      chromatography with an average yield of 1.4 mg/L culture of purified hGH,
      independent of secretion signal. Purified pelB- and ompA-hGH are monomeric based
      on size exclusion chromatography with an intact mass corresponding to mature hGH
      indicating proper cleavage of the signal peptide and folding in the periplasm.
      Both pelB- and ompA-hGH bind the hGH receptor with high affinity and potently
      stimulate Nb2 cell growth. These results demonstrate that the pET expression
      system is suitable for the rapid and simple isolation of bioactive, soluble hGH
      from E. coli.

PMID- 23168095
TI  - Cervicothoracic reconstruction with an anteromedial thigh flap: a novel flap
      concept.
AB  - The anteromedial thigh region is more popular as a donor site for skin graft than
      for flap. It is an extended area whose limits are poorly defined. This explains
      why flaps vascularised by different source arteries but described under the same
      name can be found in the literature introducing confusion and misunderstanding.
      This confusion was introduced since the primary descriptions as Baek presented in
      1983 an anteromedial skin flap whose source artery was the superficial femoral
      artery and Song published a year later, under the same name, a flap vascularised
      by the innominate descending branch of the lateral circumflex femoral artery.
      Whatever the name and the source artery, the anteromedial thigh region is an
      under-exploited region which can be useful in the case of composite and complex
      defects. Anteromedial thigh flaps, either as pedicled or as a microvascular free
      tissue transfer, were used in reconstructive surgery. We here describe a chimeric
      flap of the anteromedial thigh region and used as a flow-through flap.

PMID- 23168096
TI  - A study on the association of TNF-alpha(-308), IL-6(-174), IL-10(-1082) and IL
      1Ra(VNTR) gene polymorphisms with rheumatic heart disease in Pakistani patients.
AB  - Inflammation is an important contributor to the pathogenesis of rheumatic heart
      disease (RHD), a disorder of heart valves caused by a combination of immune,
      genetic and environmental factors. Cytokines are important mediators of
      inflammatory and immune responses. The aim of this study was to investigate the
      role of cytokine gene polymorphisms and their potential usefulness as biomarkers
      in RHD patients from Pakistan. We screened 150 RHD patients and 204 ethnically
      matched controls for tumor necrosis factor (TNF)-alpha(-308)G/A, interleukin (IL)
      10(-1082) G/A, interleukin (IL)-6(-174) G/C and a variable number of tandem
      repeats (VNTRs) polymorphism of the IL-1Ra gene using polymerase chain reaction.
      The results showed that TNF-alpha(-308) A and IL-6(-174) G alleles were
      associated with susceptibility to RHD (p=0.000; OR=2.81; CI=1.5-5.14 and p=0.025;
      OR=1.50; CI=1.04-2.16 respectively). The TNF-alpha(-308) AA and GA genotypes were
      associated with susceptibility to RHD (p=0.012; OR=9.94; CI; 1.21-217.3 and
      p=0.046; OR=1.97; CI=0.98-3.97 respectively) while the GG genotype seemed to
      confer resistance (p=0.003; OR=0.39; CI=0.20-0.76). The GG genotype for IL-6(
      174) was significantly associated with predisposition to RHD (p=0.015; OR=2.6;
      CI=1.17-5.85). The A1 (four repeats) and A2 (two repeats) alleles at the IL-1Ra
      VNTR polymorphism were associated with resistance and susceptibility to RHD
      respectively. However, this polymorphism deviated from Hardy-Weinberg equilibrium
      in both patients and controls in our population. TNF-alpha(-308) and IL-6(-174)
      polymorphisms may be useful markers for the identification of individuals
      susceptible to RHD in Pakistan. These individuals could be provided aggressive
      prophylactic intervention to prevent the morbidity and mortality associated with
      RHD.

PMID- 23168099
TI  - Medical screenings in dental settings.
AB  - The purpose of Linking Research to Clinical Practice is to present evidence based
      information to clinical dental hygienists so that they can make informed
      decisions regarding patient treatment and recommendations. Each issue will
      feature a different topic area of importance to clinical  dental hygienists with
      A BOTTOM LINE to translate the research findings into clinical application.

PMID- 23168100
TI  - The role of dental hygienists in conducting rapid HIV testing.
AB  - PURPOSE: In the U.S., an estimated 21% of people living with HIV/AIDS do not know
      their positive HIV status. Expanding rap id HIV testing in the dental setting may
      increase the number of individuals who are aware of their HIV status and can
      begin medical care and social support services if seropositive and appropriate.
      As a member of the dental team, the dental hygienist, with the proper knowledge
      and training, may be suitable to conduct rapid HIV testing.

PMID- 23168101
TI  - Treatment modalities for drug-induced gingival enlargement.
AB  - PURPOSE: This paper identifies 3 specific classifications of commonly prescribed
      medications that are known to cause gingival enlargement and describes surgical
      and non-surgical treatment therapies. Primary risks associated with drug-induced
      gingival enlargement,  including increased dental decay and periodontal disease
      are also discussed.  The precise bacterial etiology in gingival enlargement
      remains unclear, although sufficient evidence exists to support the role of good
      oral hygiene in decreasing the incidence and severity of gingival enlargement 
      and improving overall gingival health. Etiology, treatment planning and
      coordination of care between physician, dentist or dental hygienist when
      indicated are important factors determining whether a surgical or non-surgical
      course of treatment should be considered.

PMID- 23168102
TI  - Tooth jewelry in an 8 year old child: case report.
AB  - PURPOSE: The number of perioral/oral body modifications has been increasing over
      the previous 30 years. The dental impact upon adults and adolescents has been
      documented previously. The purpose of this case study was to report the dental
      impact of a child's self-reported  tooth decoration. The study is a case report
      of an 8-year old child who reported for dental care with discomfort in the
      mandibular left second primary molar. She embedded a stick-on rhinestone stud
      into the tooth for aesthetics. It fractured the tooth and led to its loss.
      Anticipatory  guidance about perioral/oral body modification risks to children,
      as well as to adolescents and adults, should be included in the discussion of
      interventions that influence oral wellness.

PMID- 23168103
TI  - A randomized controlled trial of the effect of standardized patient scenarios on
      dental hygiene students' confidence in providing tobacco dependence counseling.
AB  - PURPOSE: Dental hygienists report a lack of confidence in initiating Tobacco
      Dependence Counseling (TDC) with their patients who smoke. The purpose of this
      study was to determine if the confidence of dental hygiene students in providing
      TDC can be increased by Standardized Patient  (SP) training, and if that
      confidence can be sustained over time. METHODS: This 2-parallel group randomized
      design was used to compare the confidence of students receiving SP training to
      stu dents with no SP training. After a classroom lecture, all subjects (n=27)
      received  a baseline test of knowledge and confidence. Subjects were randomly
      assigned to test and control groups with equivalent mean knowledge scores. The
      test group subjects participated in a SP TDC session. Both groups gained parallel
      experience to treating patients who were smokers and giving TDC  in clinical
      scenarios during the 6 month time period. One week end-training and 6 month post
      training assessments were administered to both groups. ANCOVA compared mean
      confidence scores. RESULTS: End-training scores at 1 week showed a statistically
      significant  increase (p=0.002) in overall mean confidence following SP training
      for individuals in the test group. The 6 month follow-up test results showed a
      slight decline in confidence scores among subjects in the test group and an
      overall gain in confidence for control group participants. However,  overall
      confidence scores were comparable for the groups. CONCLUSION: SP training
      improved dental hygiene students' initial confidence in providing TDC and was
      sustained, but not to a significant degree. Clinical experience alone increased
      confidence. Further studies may help determine  how the initial confidence gained
      by SP training can be sustained and what the role of clinical experience plays in
      overall confidence in providing TDC.

PMID- 23168104
TI  - Maryland dental hygienists' knowledge, opinions and practices regarding dental
      caries prevention and early detection.
AB  - PURPOSE: The purpose of this study was to assess Maryland dental hygienists'
      knowledge, practices and opinions regarding dental caries prevention and early
      detection. METHODS: A 30 item survey was mailed to 1,258 Maryland dental
      hygienists. Two follow-up mailings  and email reminders were sent. RESULTS: The
      response rate was 43% (n=540). Nearly all respondents were female (98%), and 58%
      practiced in solo settings. Knowledge and certainty of knowledge were moderate:
      sealants are needed regardless of topical fluoride use (55% certain, 40% less 
      certain), newly erupted permanent molars are the best candidates for sealants
      (54%, 36%) and professionally applied fluorides are desirable in areas without
      fluoridated water (55%, 36%). Fewer were certain that incipient lesions can be
      remineralized before cavitation (23%, 69%), and dilute,  frequently administered
      fluorides are more effective in caries prevention than concentrated, less
      frequently administered fluorides (6%, 24%). Opinions regarding effectiveness of
      protocols for 2 age groups from 6 months to 6 years, the challenges of early
      childhood caries (ECC), prevention  practices regarding sealant and topical
      fluoride applications varied widely. Eighty-nine percent reported routinely
      assessing dental caries risk factors of child patients and 90% were interested in
      continuing education courses. There were no significant differences between
      different  types of practice settings, year of graduation, race/ethnicity or
      gender. CONCLUSION: Knowledge of recommended guidelines for fluoride and sealant
      application support clinical decision-making and self-care counseling.
      Misinformation and lack of understanding of current  research and recommendations
      identify a need for educational interventions in undergraduate dental hygiene
      programs and through continuing education for practicing hygienists.

PMID- 23168105
TI  - Dental hygienist attitudes toward providing care for the underserved population.
AB  - PURPOSE: The purpose of this study was to investigate registered dental
      hygienists' attitude toward community service, sensitivity to patient needs, job
      satisfaction and their frequency to volunteer care for the underserved
      population. METHODS: A 60 question survey  instrument was developed and
      distributed to 306 participants. The survey instrument ad dressed the following
      variables: community service, sensitivity to patient needs, job satisfaction,
      social responsibility, spirituality and willingness to volunteer care. A total of
      109 surveys were returned  yielding a 33.9% response rate. SPSS version 19.0 was
      utilized for data analysis. Based on the factor analysis, the 6 original
      variables were reduced to 3 variables, which included attitude toward community
      service, job satisfaction and sensitivity to patient needs. RESULTS: For 
      registered dental hygienists their level of education, membership in their
      professional association, attitude toward community service and sensitivity to
      patients were associated with their frequency of volunteering care for the
      underserved population. Additionally, a discriminant analysis  indicated a strong
      prediction among registered dental hygienists attitude toward community service
      and job satisfaction to their frequency of volunteering care for the underserved
      population. CONCLUSION: This research study of the factors that influence
      registered dental hygienists'  frequency of volunteering care indicates how
      important oral health care preparatory norms and dispositions are to the
      underserved population. Understanding what persuades registered dental hygienists
      to volunteer care provides valuable information to registered dental hygienists,
      as well as  dental hygiene programs regarding volunteering care for the
      underserved population and the importance of attitudes toward community service,
      sensitivity to patient needs and job satisfaction.

PMID- 23168106
TI  - Effects of dental magnification lenses on indirect vision: a pilot study.
AB  - PURPOSE: The purpose of this pilot study was to evaluate the effect of
      magnification lenses on the indirect vision skills of dental hygiene students.
      METHODS: This pilot study examined the accuracy and efficiency of dental hygiene
      students' indirect vision skills while  using traditional safety lenses and
      magnification lenses. The sample was comprised of 14 students in their final
      semester of a dental hygiene program. A crossover study approach was utilized,
      with each participant randomly assigned to a specific order of eyewear. The study
      included evaluation  of each participant taking part in 2 separate clinical
      sessions. During the first session, each participant completed a clinical
      exercise on a dental manikin marked with 15 dots throughout the oral cavity while
      wearing the randomly as signed eyewear, and then completed a similar exercise on 
      a differently marked dental manikin while wearing the randomly assigned eyewear.
      This procedure was repeated at a second clinical session, however, the dental
      manikin and eyewear pairings were reversed. Accuracy was measured on the number
      of correctly identified dots and efficiency was measured  by the time it took to
      identify the dots. Perceptions of the participants' use of magnification lenses
      and the participants' opinion of the use of magnification lenses in a dental
      hygiene curriculum were evaluated using a questionnaire. RESULTS: Comparing the
      mean of the efficiency  scores, students are more efficient at identifying
      indirect vision points with the use of magnification lenses (3 minutes, 36
      seconds) than with traditional safety lenses (3 minutes, 56 seconds). Comparing
      the measurement of accuracy, students are more accurate at identifying indirect
      vision  points with traditional safety lenses (84%) as com pared to magnification
      lenses (79%). Overall, the students report ed an increased quality of dental
      hygiene treatment provided in the clinical setting and an improved clinical
      posture while treating patients with the use of magnification lenses. CONCLUSION:
      This study did not produce statistically significant data to support the use of
      magnification lenses to enhance indirect vision skills among dental hygiene
      students, however, students perceived that their indirect vision skills were
      enhanced by the use of magnification lenses.

PMID- 23168109
TI  - Associations between changes in anthropometric measures and mortality in old age:
      a role for mid-upper arm circumference?
AB  - OBJECTIVES: In elderly individuals, little is known about changes in different
      anthropometric measures with respect to mortality. We examined the association
      between changes in eight anthropometric measures and mortality in an elderly
      population. DESIGN: Longitudinal study including baseline measurements in 1988
      1990 and repeated measures in 1993. SETTING: European towns. PARTICIPANTS: A
      total of 1061 older adults born in 1913-1918 from the Survey in Europe on
      Nutrition and the Elderly, A Concerted Action study were included in this study.
      MEASUREMENTS: Weight, body mass index, waist circumference, waist to hip ratio,
      waist to height ratio, mid-upper arm circumference (MUAC), triceps skinfold
      thickness, and corrected arm muscle area were taken during both measurements.
      RESULTS: A Cox regression model was used to examine the association between
      anthropometric changes (divided into quintiles, smallest change = reference
      category) and all-cause and cardiovascular disease mortality over approximately 6
      years of follow-up, adjusted for baseline measurement of application, age, sex,
      smoking, education, physical activity, and major chronic diseases. A decrease in
      weight (>=3.2 kg), waist circumference (>=3.1 cm), and MUAC (>=1.6 cm and 0.6-1.6
      cm) were (near) significantly associated with an all-cause mortality risk of 1.48
      (95% CI: 0.99-2.20), 1.52 (95% CI: 1.01-2.31), 1.81 (95% CI: 1.17-2.79), and 1.66
      (95% CI: 1.10-2.49), respectively. Also for MUAC, an increase (>=1.3 cm) was
      significantly associated with an increased all-cause and cardiovascular disease
      mortality risk [hazard ratio, 1.52 (95% CI: 1.00-2.31) and 1.94 (95% CI: 1.00
      3.75), respectively]. CONCLUSION: Associations were observed for decreases in
      only 3 of 8 anthropometric measures and all-cause mortality. Decreases in MUAC
      had the strongest association with mortality and was the only measure in which an
      increase also was associated with mortality. This suggests a role for MUAC in the
      prediction of mortality in elderly individuals.

PMID- 23168110
TI  - Developing future nursing home medical directors: a curriculum for geriatric
      medicine fellows.
AB  - Long term care facilities are important sites of care for elderly adults. Despite
      a growing need and interest in medical direction in nursing homes, there have
      been limited educational opportunities in this area for geriatric medicine
      fellows. This article describes a novel medical director's curriculum for first
      year geriatric medicine fellows to prepare them for the role of nursing home
      medical director. This novel curriculum has been integrated into the Department
      of Geriatric Medicine's Fellowship training program at the John A. Burns School
      of Medicine, University of Hawaii. The curriculum consists of seven seminars that
      have been integrated into the didactic sessions during the first year of
      fellowship. Core content areas include: (1) roles and responsibilities of the
      medical director, (2) infection control, (3) physician documentation, (4) federal
      regulations and state surveys, (5) quality improvement, (6) culture change in
      nursing homes, and (7) transitions in care. All topics were discussed using the
      framework described by the American Medical Directors Association's position
      statement on the roles and responsibilities of the nursing home medical director.
      To our knowledge, this is the first curriculum in the medical literature that is
      designed to prepare geriatric medicine fellows for roles as medical directors in
      nursing homes.

PMID- 23168111
TI  - Minimum Data Set 3.0: a big step forward.

PMID- 23168112
TI  - The prevalence and course of neuropsychiatric symptoms in nursing home patients
      with dementia: a systematic review.
AB  - BACKGROUND: Persons with dementia frequently exhibit neuropsychiatric symptoms
      (NPSs). Previous studies have indicated that the prevalence is particularly high
      in nursing home (NH) patients. However, differences in methodology in studies of
      the prevalence and course of NPSs have made it difficult to compare their
      results. METHODS: We searched the electronic databases MEDLINE, EMBASE, PsycINFO,
      Ovid Nursing, and AgeLine from their inception until July 2012 using medical
      subject headings to identify studies that reported figures on the prevalence and
      course of NPSs in NH patients with dementia. RESULTS: A total of 28 studies met
      the inclusion criteria. In total, 8468 and 1458 persons participated in the
      prevalence and longitudinal studies, respectively. The weighted mean prevalence
      of having at least one NPS was 82%. Although the prevalence of individual
      symptoms varied, the highest prevalence figures were found for agitation and
      apathy. The persistence of individual NPSs varied substantially, but in these
      studies, having at least one NPS was highly persistent across the studies.
      CONCLUSION: This review confirms that clinically significant NPSs are common in
      NH patients with dementia. Even though great variability exists across studies,
      recent studies applying similar methodology have made comparisons between studies
      feasible, revealing relatively consistent prevalence patterns for individual
      symptoms. The natural course of symptoms deserves closer attention. This is vital
      in planning prevention and treatment of NPSs in NH patients with dementia.

PMID- 23168114
TI  - Stiripentol is anticonvulsant by potentiating GABAergic transmission in a model
      of benzodiazepine-refractory status epilepticus.
AB  - Benzodiazepines (BZDs) are first-line therapy for treatment of status epilepticus
      (SE). However, BZD treatment is negatively affected by seizure duration due to
      decreases in BZD-sensitive GABA(A) receptors during prolonged SE. Stiripentol
      (STP) is an anticonvulsant that is used as add-on treatment for Dravet Syndrome.
      Recent studies have shown that STP is a positive allosteric modulator of the
      GABA(A) receptor. The subunit selectivity of STP at this receptor suggests that
      it would be anticonvulsant in both brief as well as prolonged SE. We tested this
      possibility by comparing the ability of STP and diazepam (DZP), a commonly used
      BZD, to terminate behavioral convulsions in a rodent model of pharmacoresistant
      SE. We found that STP was anticonvulsant in this model and remained effective
      during prolonged SE, unlike DZP which exhibited a 14 fold increase in its ED(50).
      Whole cell recording from hippocampal slices from these animals revealed that STP
      potentiated GABAergic IPSCs, as well as tonic GABAergic current by acting at a
      site on the GABA(A) receptor separate from the BDZ binding site. Potentiation of
      GABAergic currents by STP remained intact during prolonged SE, while potentiation
      by DZP was lost. Both IPSC potentiation and anticonvulsant activity of STP were
      greater in younger animals than in adults. These findings suggest that at doses
      that yield therapeutically relevant concentrations, STP is anticonvulsant by
      potentiating GABAergic inhibition and that the subunit selectivity profile of STP
      enables it to remain effective despite GABA(A) receptor subunit changes during
      prolonged SE.

PMID- 23168115
TI  - Regulation of serotonin (5-HT) function by a VGLUT1 dependent glutamate pathway.
AB  - Unraveling the mechanisms of 5-HT neuron control might provide new insights into
      depression pathophysiology. In addition to the inhibitory 5-HT1A autoreceptors,
      cortico-raphe glutamatergic descending pathways are suggested to modulate 5-HT
      activity in the DRN. Here we studied how decreased VGLUT1 levels in the brain
      stem affect glutamate regulation of 5-HT function. VGLUT1+/- mice (C57BL/6) and
      wild type (WT) littermates were used. VGLUT1 expression in the DRN, 5-HT turnover
      and immuno histochemical analysis of neuronal activity in different areas was
      studied. Moreover, the functionality of the inhibitory 5-HT1A autoreceptor was
      assessed using electrophysiological, biochemical and pharmacological approaches.
      VGLUT1 immunoreactivity was markedly lower in the DRN of the VGLUT1+/- mice and
      specifically, in the surroundings of GABA and 5-HT cell bodies. These mice showed
      decreased induced neuronal activity in 5-HT cells bodies and in different
      forebrain areas, as well as decreased hippocampal cell proliferation and 5-HT
      turnover. Further, 5-HT1A autoreceptor desensitization was evidenced by
      electrophysiological studies, GTP-gamma-S coupling to 5-HT1A autoreceptor and a
      lower hypothermic response to 5-HT1A activation. This study shows first time that
      VGLUT1 dependent glutamate innervation of the DRN could modulate 5-HT function.

PMID- 23168113
TI  - Positive allosteric modulator of alpha7 nicotinic-acetylcholine receptors, PNU
      120596 augments the effects of donepezil on learning and memory in aged rodents
      and non-human primates.
AB  - The development of novel therapeutic agents for disorders of cognition such as
      Alzheimer's disease (AD) is of paramount importance given the ever-increasing
      elderly population, however; there is also considerable interest in any strategy
      that might enhance the clinical efficacy of currently available treatments. The
      purpose of this study was to evaluate an adjunctive treatment strategy to memory
      enhancement, namely combining the commonly prescribed acetylcholinesterase
      inhibitor (AChEI) donepezil, with a positive allosteric modulator (PAM) of alpha7
      nicotinic-acetylcholine receptors (alpha7-nAChRs), PNU-120596. The treatment
      strategy was evaluated in a (non-spatial) spontaneous novel object recognition
      (NOR) task in young rats; a water maze spatial learning and recall procedure in
      aged, cognitively-impaired rats, and a delayed match to sample (working/short
      term memory) task in aged rhesus monkeys. In all three experiments a similar drug
      response was observed, namely that donepezil administered alone improved task
      performance in a dose-dependent manner; that PNU-120596 administered alone was
      without significant effect, but that the combination of PNU-120596 with a
      subthreshold dose of donepezil was effective. The positive effect of the drug
      combination appeared to be alpha7-nAChR mediated given that it was blocked in the
      NOR task by the selective alpha7-nAChR antagonist methyllycaconitine (MLA).
      Collectively, these data indicate that PNU-120596 increases the effective dose
      range of donepezil in learning/memory-related tasks in young and age-impaired
      animal models. The results suggest that alpha7-nAChR-selective PAMs like PNU
      120596 have potential as adjunctive treatments with acetylcholinesterase
      inhibitors (e.g., donepezil) for age-related illnesses such as AD as well memory
      disorders not necessarily associated with advanced age.

PMID- 23168116
TI  - Endoscopic therapy of Barrett esophagus.
AB  - Barrett esophagus (BE) is a well-established premalignant condition for
      esophageal adenocarcinoma (EAC), a lethal cancer with a dismal survival rate. The
      current guidelines recommend surveillance of patients with BE to detect dysplasia
      or early cancer before the development of invasive EAC. Recently, endoscopic
      eradication therapies have been shown to be safe and effective in the treatment
      of BE-related high-grade dysplasia and early EAC. This article reviews the
      various treatment options for BE and discusses the current evidence and gaps in
      knowledge in the understanding of treatment of this condition. In addition,
      recommendations are provided in context to the recently published guidelines by
      the American Gastroenterological Association.

PMID- 23168117
TI  - Advances in endoluminal therapy for esophageal cancer.
AB  - Advances in endoscopic therapy have resulted in dramatic changes in the way early
      esophageal cancer is managed as well as in the palliation of dysphagia related to
      advanced esophageal cancer. Endoscopic mucosal resection (EMR) and endoscopic
      submucosal dissection (ESD) are effective therapies for accurate histopathologic
      staging and provide a potential for complete cure. Mucosal ablative techniques
      (radiofrequency ablation and cryotherapy) are effective adjuncts to EMR and ESD
      and reduce the occurrence of synchronous and metachronous lesions within the
      Barrett esophagus. The successes of these techniques have made endoscopic therapy
      the primary means of management of early esophageal cancer.

PMID- 23168118
TI  - Endolumenal therapies for gastroesophageal reflux disease.
AB  - TIF Stretta and Endocinch all seem technically safe in well-selected patients
      including those with prior esophageal and gastric surgeries. Long-term
      effectiveness is being evaluated. Given the current enthusiasm for increasingly
      less invasive surgical techniques, the inertia for endolumenal therapies
      continues to grow. Other endolumenal therapies for Gastroesophageal reflux
      disease (GERD) have initiated trials. These pursue similar fundoplication or
      lower esophageal sphincter reconstruction using simpler techniques with fewer
      steps. Because all endolumenal approaches to GERD evolve, objective evaluation
      for symptom resolution and reduced esophageal acid exposure with improved
      esophagogastric physiology will remain a constant.

PMID- 23168119
TI  - Achalasia.
AB  - Endoscopic therapy for achalasia is centered on disrupting or weakening the lower
      esophageal sphincter. The three traditional treatment options for achalasia are
      surgical myotomy, pneumatic dilation, and botulinum toxin injection. Pneumatic
      dilation yields results that are generally better than botulinum toxin injection
      and may approach a clinical response comparable with surgery. Per oral endoscopic
      myotomy is a newer endoscopic modality that will likely change the treatment
      paradigm for achalasia.

PMID- 23168120
TI  - Early gastric cancer and dysplasia.
AB  - Since the concept of early gastric cancer was first described in Japan in 1962,
      its treatment has evolved from curative surgical resection to endoscopic
      resection, initially with polypectomy to more recently with endoscopic submucosal
      dissection. As worldwide experience with these endoscopic techniques evolve and
      gain acceptance, studies have confirmed its comparable effectiveness with
      historical surgical outcomes in carefully selected patients. The criteria for
      endoscopic resection have expanded to offer more patients improved quality of
      life, avoiding the morbidity and mortality associated with surgery. This article
      summarizes the evolutional role of endoscopic and surgical therapy in early
      gastric cancer.

PMID- 23168121
TI  - Endoscopic diagnosis and management of ampullary lesions.
AB  - Most (>95%) ampullary lesions are adenomas or adenocarcinomas. Side viewing
      endoscopy, endoscopic ultrasound, and endoscopic retrograde
      cholangiopancreatography are complementary procedures that have an important role
      in the diagnosis, staging, and treatment of ampullary lesions. Here the authors
      review their epidemiology and discuss the evidence for endoscopic modalities,
      with an emphasis on techniques for endoscopic resection. Although endoscopic
      papillectomy represents one of the highest-risk endoscopic interventions, it has
      largely replaced surgical modalities for the treatment of adenomatous lesions.
      Appropriate patient selection and use of preventive maneuvers will minimize the
      likelihood of persistent or recurrent lesions and postprocedure complications.

PMID- 23168122
TI  - Small bowel polyps, arteriovenous malformations, strictures, and miscellaneous
      lesions.
AB  - Deep endoscopic access using double- and single-balloon enteroscopes and
      rotational endoscopy has vastly improved endoscopic therapeutic options in the
      small intestine. In this new era of interventional enteroscopy, significant
      advances have been made in the endoscopic treatment of small bowel polyps,
      angioectasias, and strictures. Although a decade ago small bowel polyps arising
      in the setting of a polyposis syndrome such as Peutz-Jeghers would have
      necessitated surgical resection, today endoscopic resection can typically be
      performed with positive clinical results. This article describes the current
      endoscopic management of small bowel polyps, arteriovenous malformations,
      strictures, and miscellaneous lesions identified within the small intestine.

PMID- 23168123
TI  - Endoscopic therapy for postoperative leaks and fistulae.
AB  - Endoscopic techniques for the treatment of postoperative fistulae and leaks are
      rapidly developing. Conventional surgical therapy for postsurgical leaks and
      fistulae is associated with significant morbidity and mortality. Novel endoscopic
      therapies have demonstrated safety, despite the inherent challenges of
      intervention in this patient population, and are steadily building evidence for
      efficacy relative to surgical management. The article examines endoscopic therapy
      for leaks and fistulae after esophageal, gastric, bariatric, colonic, and
      pancreaticobiliary surgery.

PMID- 23168124
TI  - Endoscopic resection of large colon polyps.
AB  - Endoscopic resection, including polypectomy, endoscopic mucosal resection, and
      endoscopic submucosal dissection, is the preferred treatment method of large
      colorectal polyps. Its safety and efficacy have been shown. Endoscopic removal
      techniques are important because they provide a resection specimen for precise
      histopathologic staging to further direct diagnosis, prognosis, and management
      decisions. Used according to its indications, it provides curative resection and
      obviates the higher morbidity, mortality, and cost associated with alternative
      surgical treatment.

PMID- 23168125
TI  - Enteral stents in malignant bowel obstruction.
AB  - Colorectal stent placement offers a minimally invasive approach for relief of
      malignant bowel obstruction. Stent placement is safe and effective in carefully
      selected patients as a bridge to surgery or for definitive palliation of
      obstruction. Concerns remain regarding the long-term efficacy of stent placement
      and related complications. Future studies are needed to identify patients who are
      the best candidates for stent placement.

PMID- 23168126
TI  - Endoscopy in the management of obesity.
AB  - Obesity affects more than one third of adults in the United States and is
      associated with increased morbidity, mortality, and health care costs compared
      with normal weight adults. Current therapies include medical management
      consisting of therapeutic lifestyle change and pharmacotherapy, which has limited
      effectiveness, and bariatric surgery, which is currently the most effective
      therapy, but is limited by complications, long-term weight regain, and limited
      access. Endoscopic therapies are currently under investigation to treat weight
      regain after bariatric surgery and as a primary treatment for obesity, addressing
      the current gap in the treatment of obesity.

PMID- 23168127
TI  - Gastrointestinal Endoscopy Clinics of North America. Endolumenal therapy.
      Foreword.

PMID- 23168128
TI  - Endolumenal therapy of gastrointestinal disorders.

PMID- 23168130
TI  - Spermatological characteristics of Elstia stossichianum (Digenea, Mesometridae)
      from the intestine of the cow bream (Sarpa salpa) off Dakar, Senegal.
AB  - The current study was designed to increase the spermatological ultrastructural
      database on Digenea, thus contributing to the future establishment of
      phylogenetic relationships within this group based on ultrastructural
      characteristics of both spermiogenesis and spermatozoa. Spermiogenesis in Elstia
      stossichianum begins with the formation of a differentiation zone containing two
      centrioles, two striated rootlets, a nucleus, several mitochondria and an
      intercentriolar body constituted by seven electron-dense layers. Each centriole
      develops into a free flagellum growing orthogonally to the median cytoplasmic
      process. Proximo-distal fusion of the flagella with the median cytoplasmic
      process occurs after flagellar rotation. Both nucleus and mitochondria migrate
      before the complete proximo-distal fusion of both flagella with the median
      cytoplasmic process. Finally, the constriction of the ring of arched membranes
      gives rise to the young spermatozoon. The mature spermatozoon of E. stossichianum
      exhibits two axonemes of different length of the 9+'1' trepaxonematan pattern, a
      nucleus, a mitochondrion, two bundles of parallel cortical microtubules, external
      ornamentation of the plasma membrane, a lateral expansion, spine-like bodies,
      cytoplasmic ornamented buttons and granules of glycogen. The formation of
      cytoplasmic ornamented buttons during the final stages of spermiogenesis is
      reported here for the first time. 

PMID- 23168131
TI  - Strategic retrieval and retrieval orientation in reality monitoring studied by
      event-related potentials (ERPs).
AB  - Reality monitoring requires the differentiation between perceived and imagined
      events or between our own actions and the actions of others. The role of control
      processes in reality monitoring is yet not fully understood. In the current event
      related potential (ERP) study, we investigated such control processes in the form
      of retrieval orientation and strategic retrieval of nontarget information. At
      study, complete or incomplete object words were presented in sentences.
      Participants had to identify the words as the subject of the sentence (perceive
      condition) or had to complete them upon presentation of a word fragment (self
      generate condition). The participants' memory accuracy was better for generated
      items than for perceived items, as tested in a subsequent memory exclusion task.
      Comparison of ERPs to new items between the two test conditions (i.e. assessing
      retrieval orientation) showed more positive ERPs when generated object names were
      targeted. Retrieval orientation also modulated the early midfrontal old/new
      effect: Items of the self-generate condition elicited this effect irrespective of
      their target/nontarget status, while in response to the less well remembered
      items of the perceive condition it was only found when these items were defined
      as targets. Target retrieval (as reflected in the left-parietal old/new effect)
      occurred in both test conditions, but nontarget retrieval was observed only for
      generated items (when perceived items were targeted). Current findings indicate
      that retrieval orientation can modulate familiarity-related processes. The
      selective occurrence of nontarget retrieval for generated items corroborates the
      concept that the ease with which nontarget information can be accessed promotes
      nontarget retrieval.

PMID- 23168129
TI  - The role of the amygdala in the pathophysiology of panic disorder: evidence from
      neuroimaging studies.
AB  - Although the neurobiological mechanisms underlying panic disorder (PD) are not
      yet clearly understood, increasing amount of evidence from animal and human
      studies suggests that the amygdala, which plays a pivotal role in neural network
      of fear and anxiety, has an important role in the pathogenesis of PD. This
      article aims to (1) review the findings of structural, chemical, and functional
      neuroimaging studies on PD, (2) relate the amygdala to panic attacks and PD
      development, (3) discuss the possible causes of amygdalar abnormalities in PD,
      (4) and suggest directions for future research.

PMID- 23168132
TI  - Chemokines shape the immune responses to tuberculosis.
AB  - Mycobacterium tuberculosis (Mtb) is the intracellular pathogen that causes the
      disease, tuberculosis. Chemokines and chemokine receptors are key regulators in
      immune cell recruitment to sites of infection and inflammation. This review
      highlights our recent advances in understanding the role of chemokines and
      chemokine receptors in cellular recruitment of immune cells to the lung, role in
      granuloma formation and host defense against Mtb infection.

PMID- 23168133
TI  - Cytokine response of human mononuclear cells induced by intestinal Clostridium
      species.
AB  - Altered composition of intestinal microbiota has been associated with various
      immunological disorders such as inflammatory bowel disease. Although Clostridium
      species are major inhabitants of the intestinal tract, their interaction with the
      host immunological system is yet poorly characterized. In this study, cytokine
      responses of human monocytic cell line THP-1 and peripheral blood mononuclear
      cells (PBMC) to six type strains representing common intestinal clostridial
      species were determined. The strains induced diverse cytokine responses in both
      THP-1 cells and PBMC. Clostridium perfringens was the most potent inducer of both
      tumour necrosis factor alpha (TNF-alpha) and interleukin-10 (IL-10), as compared
      to Clostridium histolyticum, Clostridium clostridioforme, Clostridium leptum,
      Clostridium sporosphaeroides and Blautia coccoides. Interleukin-8 (IL-8)
      production in PBMC was most efficiently stimulated by C. sporosphaeroides. The
      same PBMC preparations that responded strongly to Escherichia coli
      lipopolysaccharide (LPS) also responded strongly to bacterial stimulation. This
      indicates that the level of responsiveness is an individual feature of
      mononuclear cell preparations, and that the overall cytokine response is composed
      by a combination of host factors and microbial structures affecting them. This
      work supports the idea that the composition of the intestinal clostridial
      population influences immune responses and is likely to play an important role in
      intestinal homeostasis.

PMID- 23168135
TI  - Backfilling of iliac crest defects with hydroxyapatite-calcium triphosphate
      biphasic compound: a prospective, randomized computed tomography and patient
      based analysis.
AB  - BACKGROUND CONTEXT: Hydroxyapatite-calcium triphosphate (HCT) biphasic compounds
      are known to be efficacious in filling bone voids. No large study to date has
      assessed their radiographic efficacy in iliac crest voids with computed
      tomography (CT) analysis at a 2-year follow-up. PURPOSE: To assess whether
      backfilling iliac crest defects with HCT biphasic compound decreases donor site
      pain and what effect backfilling has on CT appearance of the donor ilium. STUDY
      DESIGN: Prospective randomized clinical trial. PATIENT SAMPLE: Adult patients
      with spinal disorders undergoing spinal arthrodesis requiring posterior iliac
      crest bone grafting. OUTCOME MEASURES: Physician-administered visual analog scale
      (VAS) and pre- and postoperative CT analysis was performed. METHODS: This
      prospective, randomized, single-blind study followed patients requiring
      nonstructural posterior iliac crest harvest as part of spinal disorder treatment
      for 2 years. The harvest technique preserved both cortical tables and their
      periostea. All patients were randomized to backfill of HCT or no backfill. All
      patients had a CT of the pelvis immediately postoperative and at the 2-year
      follow-up. Computed tomography analysis was performed by a board-certified
      neuroradiologist. Analysis included qualitative assessment of the ilia appearance
      and defect density quantified in Hounsfield units. All patients completed VAS of
      their donor site pain (0-10, from low to high) at 6 weeks and 2 years
      postoperatively. RESULTS: Thirty-seven of 40 (17 women and 20 men) subjects
      returned for a mean 23.9-month follow-up (range, 22-29 months). The average age
      was 51.7 years (range, 27-79 years). Eighteen patients were in the backfill group
      (BF) and 19 were in the control group (C). There was no statistically significant
      difference in pain at 6 weeks or 2 years between the two groups. Bone density
      significantly decreased from postoperative to 2 years in BF (implying resorption
      of HCT and replacement of host bone) and significantly increased in C (implying
      reformation of host bone). Both groups had similar cortical defect repair. The
      backfill group had significantly better medullary defect repair (p<.01, Fisher
      exact test). CONCLUSIONS: Backfilling iliac crest voids with HCT biphasic
      compound does not significantly decrease donor site pain. Both the backfilled and
      control defects reformed bone over the 2-year period, with BF having
      significantly less medullary defects than C.

PMID- 23168136
TI  - Single-stage posterior decompression and stabilization for metastasis of the
      thoracic spine: prognostic factors for functional outcome and patients' survival.
AB  - BACKGROUND CONTEXT: There are limited data analyzing radiological and clinical
      factors for the functional outcomes of surgery for spinal metastasis. Also, there
      are few studies to investigate the relationship between the functional outcome
      and the patients' survival. Thus, analysis of both functional outcomes and the
      survival with their relationship in a possibly homogenous group of patients is
      worth being reported. PURPOSE: To assess treatment outcomes of single-stage
      posterior decompression and stabilization (PDS) with or without corpectomy for
      thoracic vertebral metastases and to analyze factors affecting both the
      functional outcome and the patients' survival after the surgical intervention.
      STUDY DESIGN: Retrospective observational study. PATIENT SAMPLE: A consecutive
      series of 105 patients, who underwent the previously stated surgery for
      metastatic spinal cord compression (MSCC) of thoracic spine, were included and
      retrospectively analyzed. OUTCOME MEASURES: The postoperative functional outcomes
      were evaluated using visual analog scale and Frankel grade at postoperative 2
      weeks, and all patients were followed for survival analysis. METHODS: An
      institutional database was searched to identify all patients who underwent single
      stage PDS for thoracic metastatic spinal tumors between March 2002 and June 2010.
      Demographic data as well as preoperative and postoperative medical conditions
      were collected from medical records. Radiological findings were confirmed on
      electronic archive. Survival data were obtained either on medical records or with
      a reference to governmental cancer registry system. RESULTS: Postoperative pain
      improvement was more evident in patients receiving anterior column reconstruction
      and four or more levels of fixation (p=.02 and <0.01, respectively). Twenty-one
      patients (20%) showed improvement of the Frankel grade, and 10 of 21 Frankel C
      patients became ambulatory. The preoperative Karnofsky Performance Scale (>=70)
      and ambulatory status were significant predictors for the postoperative
      ambulatory function. After surgery, the median overall survival of the patients
      was 6.0 months. In the univariate analysis, the patient's age (younger than 60
      years), type of primary cancer (ie, moderate and slow growth), no visceral
      metastases, less than three levels of spinal metastases, and postoperative
      adjuvant therapy were positively significant for the patients' survival (p<.05).
      In the multivariate analysis, limited (less than three levels) spinal metastases
      and postoperative adjuvant therapy were proven to significantly prolong the
      patient's survival (hazard ratios of 0.53 and 0.48, respectively, p<.05).
      Although the functional outcomes did not directly influence the patients'
      survival, the patients with better functional outcome showed increased chance of
      receiving postoperative adjuvant therapy (p<.01). CONCLUSIONS: Single-stage PDS
      with or without corpectomy effectively improved the functional status of patients
      with MSCC of the thoracic spine and also afforded the patients to have more
      chances of postoperative adjuvant therapy, which was significant for patients'
      survival. Therefore, we suggest that the role of surgery in the management of
      MSCC could be not only a symptomatic palliation but also a strategy to prolong
      patients' survival.

PMID- 23168134
TI  - HIV among immigrants living in high-income countries: a realist review of
      evidence to guide targeted approaches to behavioural HIV prevention.
AB  - BACKGROUND: Immigrants from developing and middle-income countries are an
      emerging priority in HIV prevention in high-income countries. This may be
      explained in part by accelerating international migration and population
      mobility. However, it may also be due to the vulnerabilities of immigrants
      including social exclusion along with socioeconomic, cultural and language
      barriers to HIV prevention. Contemporary thinking on effective HIV prevention
      stresses the need for targeted approaches that adapt HIV prevention interventions
      according to the cultural context and population being addressed. This review of
      evidence sought to generate insights into targeted approaches in this emerging
      area of HIV prevention. METHODS: We undertook a realist review to answer the
      research question: 'How are HIV prevention interventions in high-income countries
      adapted to suit immigrants' needs?' A key goal was to uncover underlying theories
      or mechanisms operating in behavioural HIV prevention interventions with
      immigrants, to uncover explanations as how and why they work (or not) for
      particular groups in particular contexts, and thus to refine the underlying
      theories. The realist review mapped seven initial mechanisms underlying
      culturally appropriate HIV prevention with immigrants. Evidence from intervention
      studies and qualitative studies found in systematic searches was then used to
      test and refine these seven mechanisms. RESULTS: Thirty-four intervention studies
      and 40 qualitative studies contributed to the analysis and synthesis of evidence.
      The strongest evidence supported the role of 'consonance' mechanisms, indicating
      the pivotal need to incorporate cultural values into the intervention content.
      Moderate evidence was found to support the role of three other mechanisms -
      'understanding', 'specificity' and 'embeddedness' - which indicated that using
      the language of immigrants, usually the 'mother tongue', targeting (in terms of
      ethnicity) and the use of settings were also critical elements in culturally
      appropriate HIV prevention. There was mixed evidence for the roles of
      'authenticity' and 'framing' mechanisms and only partial evidence to support role
      of 'endorsement' mechanisms. CONCLUSIONS: This realist review contributes to the
      explanatory framework of behavioural HIV prevention among immigrants living in
      high-income countries and, in particular, builds a greater understanding of the
      suite of mechanisms that underpin adaptations of interventions by the cultural
      context and population being targeted.

PMID- 23168137
TI  - Indicators of domestic/intimate partner violence are structured by genetic and
      nonshared environmental influences.
AB  - One of the most consistent findings to emerge from domestic/intimate partner
      violence (IPV) research is that IPV tends to "run in the family." Social learning
      theories appear to be consistent with empirical data, but almost no attention has
      been given to alternative explanations, including that genetic factors explain
      intergenerational transmission of IPV. Data for this study were drawn from wave 4
      of the National Longitudinal Study of Adolescent Health (Add Health). Three
      indicators of IPV were measured and genetic factors accounted for 24% of the
      variance in hitting one's partner, 54% of the variance in injuring one's partner,
      and 51% of the variance in forcing sexual activity on one's partner. The shared
      environment explained none of the variance across all three indicators and the
      nonshared environment explained the remainder of the variance. These findings
      point to the importance of genetic factors in the etiology of IPV.

PMID- 23168138
TI  - Hoarding and the multi-faceted construct of impulsivity: a cross-cultural
      investigation.
AB  - The proposed hoarding disorder represents a serious psychiatric condition and
      considerable public health burden. Although tremendous strides have been made in
      understanding the phenomenology and treatment of this condition, many features
      regarding the etiology and nosology remain unclear. In particular, the
      association between impulsivity and hoarding, as well as the differential role of
      impulsivity versus compulsivity has yet to be fully considered. The current
      investigation sought to fill this gap in the literature by examining the
      relationship between hoarding and impulsivity across two independent, cross
      cultural investigations. Two separate conceptualizations of the impulsivity
      construct were considered, including the Barratt Impulsivity Scale and the UPPS
      Impulsive Behavior Scale. Across Study 1 (US young adult sample; N = 372) and
      Study 2 (German young adult sample; N = 160) results revealed that hoarding was
      associated with greater rates of impulsivity, despite controlling for
      theoretically relevant covariates. More fined-grained analyses revealed a
      differential relationship with respect to the various facets of impulsivity, such
      that hoarding was most strongly linked with attentional and motor impulsivity, as
      well as urgency (i.e., impulsive behaviors in response to negative affect) and
      lack of perseverance. When considered simultaneously, both impulsivity and non
      hoarding OCD symptoms explained unique variance in hoarding. The implications of
      impulsivity for hoarding are discussed from a classification perspective, as well
      as from a vulnerability standpoint.

PMID- 23168139
TI  - Secondary salutogenic effects in veterans whose parents were Holocaust survivors?
AB  - Addressing the ongoing controversy over inter-generational transmission of
      trauma, we examined the impact of the Nazi Holocaust on PTSD course and co-morbid
      symptoms (e.g., depression, anxiety) among offspring of survivors following their
      own adversity in two longitudinal studies. Two samples of Israeli war veterans
      included Second Generation Holocaust (i.e., SGH) survivors and comparable
      veterans with no such family history (i.e., not-SGH). Study I: 1982 Lebanon War
      veterans (N = 669) were assessed 1, 3, and 20 years after the war. Study II: 1973
      Yom Kippur War veterans (N = 343) were followed up 18, 30, and 35 years after the
      war. Results indicated that SGH endorsed higher PTSD and co-morbid symptoms
      criteria rates than not-SGH veterans in the initial post-war years but this
      pattern was reversed in the long-term, that is, lower rates were evident among
      SGH in later follow-ups. These findings suggest the development of a complex
      trauma reaction among offspring of trauma survivors. Possibly there is a
      transmission of positive trauma outcomes from one generation to the next rather
      than merely negative ones. Future studies are therefore warranted to re-evaluate
      the notion of inter-generational transmission of trauma and examine its
      components.

PMID- 23168140
TI  - A descriptive survey investigating pre-registration student nurses' perceptions
      of clinical skill development in clinical placements.
AB  - BACKGROUND: Clinical skill development is essential to nurse education. Clinical
      skills are frequently taught in higher education institutions using clinical
      simulation. It is unclear if clinical skills are subsequently consolidated and
      developed in clinical placements. OBJECTIVES: The aim of this survey was to
      evaluate pre-registration student nurses perceptions of the frequency of
      opportunities to practise, the level of supervision and assessment of, clinical
      skills in their clinical placements. DESIGN: This was a cross-sectional survey
      design using an online, self-report questionnaire including a Likert-type scale
      and open ended comments. PARTICIPANTS: Four hundred and twenty one students, from
      all year groups, from a university in the south of England on a wide variety of
      clinical placements participated. METHODS: Participants evaluated the frequency
      of opportunity to practise, level of supervision and assessment of and feedback
      on performance of specific clinical skills. Clinical skills evaluated were
      measurement of vital signs, aseptic non-touch technique, assisting with eating
      and drinking, and assisting with comfort and hygiene. Data were analysed
      utilising Statistical Package for the Social Sciences Version 19. RESULTS: The
      frequency of opportunities to practise skills in clinical placement was variable
      with some participants reporting that they never had opportunity to practise
      essential skills. Similarly the level of supervision and assessment was also
      inconsistent suggesting that participants frequently practised clinical skills
      unsupervised without being assessed as competent. CONCLUSIONS: Inconsistencies in
      clinical skill development may lead to graduates who are not work ready and as a
      result, insufficient clinical competence potentially leads to unsafe practice and
      poor patient care. This calls for stronger partnerships between educators and
      clinical areas and the prioritisation of mentor preparation and education as well
      as organisational support in terms of mentor workload planning.

PMID- 23168141
TI  - Comparison of students' perceptions of educational environment in traditional vs.
      accelerated second degree BSN programs.
AB  - BACKGROUND: Students' perceptions of their academic learning environment have
      been found to be related to their approaches to learning and learning outcomes.
      Educational environment is just beginning to be researched in nursing education
      with the vast majority of studies focusing on the clinical educational
      environment. Accelerated Bachelor of Science in Nursing (ABSN) programs for
      students who have obtained a bachelor degree are a popular nursing pedagogue.
      These programs are instituted on the belief that degreed students have the
      ability to be successful in a demanding program, are older, are adult learners
      and tend to be more motivated than their traditional counterparts. There is a
      paucity of research exploring the differences in student perceptions of the
      educational environment between the traditional and accelerated programs.
      OBJECTIVE: Explore students' perceptions of the educational environment in the
      traditional and ABSN programs within an institution and determine any
      differences. DESIGN: Comparative descriptive study. SETTING: Private school of
      Nursing in the Southwest. PARTICIPANTS: Convenience sample of 24 ABSN and 38
      traditional graduating senior students. METHODS: Invited students completed the
      Dundee Ready Education Environment Measure through the online survey application
      Qualtrics. An independent t-test was used to compare the scores. RESULTS: A total
      of 62 students completed the survey for an overall response rate of 57%. No
      statistical difference was found in students' perceptions of academic environment
      between the two groups on the total score. However, there was a statistically
      significant difference on the sub-domain pertaining to atmosphere and there were
      significant differences on 6 out of 50 individual items. CONCLUSIONS: The results
      of this study indicate that, taken in its entirety, there was no significant
      difference in student perception of educational environment between the
      traditional and accelerated cohorts at this institution as measured by the DREEM
      tool. However, there was a significant difference between the two cohorts within
      the student perception of Atmosphere sub-domain and on seven individual items.
      The DREEM tool was found to be a reliable instrument to determine students'
      perceptions of educational environment.

PMID- 23168142
TI  - Nasal irrigation as an adjunctive treatment in allergic rhinitis: a systematic
      review and meta-analysis.
AB  - BACKGROUND: Saline nasal irrigation (SNI) is often recommended as additional
      nonpharmacologic treatment, having proven its efficacy in acute and chronic
      rhinosinusitis and for therapy after sinonasal surgery. To date, however, no
      systematic review or meta-analysis exists  showing the influence of SNI on
      allergic rhinitis (AR). This study aimed to establish the impact of SNI on
      symptoms of AR in different patient groups. METHODS: We conducted a systematic
      search of Medline, Embase, Cochrane Central Register of Controlled Trials, and
      ISI Web  of Science databases for literature published from 1994 to 2010 on SNI
      in AR. Prospective, randomized, controlled trials that assessed the effects of
      SNI on four different outcome parameters were included. The evaluation focused on
      primary (symptom score) and secondary parameters (medicine  consumption,
      mucociliary clearance, and quality of life). RESULTS: Three independent reviewers
      chose 10 originals that satisfied the inclusion criteria (>400 participants
      total) from 50 relevant trials. SNI performed regularly over a limited period of
      up to 7 weeks was  observed to have a positive effect on all investigated outcome
      parameters in adults and children with AR. SNI produced a 27.66% improvement in
      nasal symptoms, a 62.1% reduction in medicine consumption, a 31.19% acceleration
      of mucociliary clearance time, and a 27.88% improvement in quality  of life.
      CONCLUSION: SNI using isotonic solution can be recommended as complementary
      therapy in AR. It is well tolerated, inexpensive, easy to use, and there is no
      evidence showing that regular, daily SNI adversely affects the patient's health
      or causes unexpected side  effects.

PMID- 23168144
TI  - The creation and verification of cranial models using three-dimensional rapid
      prototyping technology in field of transnasal sphenoid endoscopy.
AB  - BACKGROUND: Surgical navigation systems have been used increasingly in guiding
      complex ear, nose, and throat surgery. Although these are helpful, they are only
      beneficial intraoperatively; thus, the novice surgeon will not have the
      preoperative training or exposure that can  be vital in complex procedures. In
      addition, there is a lack of reliable models to give surgeons hands-on training
      in performing such procedures. METHODS: A technique using an industrial rapid
      prototyping process by three-dimensional (3D) printing was developed, from which 
      accurate spatial models of the nasal cavity, paranasal sinuses (sphenoid sinus in
      particular), and intrasellar/pituitary pathology were produced, according to the
      parameters of an individual patient. Image-guided surgical (IGS) techniques on
      two different platforms were used during endoscopic  transsphenoidal surgery to
      test and validate the anatomical accuracy of the sinus models by comparing the
      models with radiological images of the patient on IGS. RESULTS: It was possible
      to register, validate, and navigate accurately on these models using commonly
      available  navigation stations, matching accurately the anatomy of the model to
      the IGS images. CONCLUSION: These 3D models can be reliably used for
      teaching/training and preoperative planning purposes.

PMID- 23168143
TI  - Aeroallergen sensitization influences quality of life and comorbidities in
      patients with nasal polyposis.
AB  - BACKGROUND: Nasal polyposis (NP) is a chronic inflammatory disease of unknown
      etiology that impairs quality of life (QoL). The role of atopy in NP is not
      established. The aim of this study was to describe the clinical characteristics
      and QoL in a broad sample of patients  with NP and to evaluate the influence of
      allergy on this disease. METHODS: A multicenter, observational, cross-sectional
      study was conducted in 67 allergy units in Spain. NP and nonsteroidal anti
      inflammatory drug (NSAID) hypersensitivity were diagnosed following EP(3)OS 
      guidelines. Rhinitis and asthma were classified following Allergic Rhinitis and
      Its Impact on Asthma and the Global Initiative for Asthma guidelines,
      respectively. Skin tests with a battery of aeroallergens were performed on all
      patients. A visual analog scale (VAS) and Short-Form 12 (SF-12)  and 31-item
      Rhinosinusitis Outcome Measure (RSOM 31) questionnaires were completed by all the
      patients. RESULTS: Of the 671 patients included, 611 were evaluable. Mean age was
      46 years and 50% of patients were men. Also, 50% were atopic. Asthma was present
      in 66% of patients  and NSAID hypersensitivity was present in 26%. The most
      frequent symptoms were nasal congestion and rhinorrhea. Mean value of VAS was
      58.6. Global health and bodily pain were the items most frequently identified in
      the SF-12 questionnaire and nasal and ocular symptoms in the RSOM-31
      questionnaire.  There was a good correlation between VAS score and QoL (p <
      0.0001). Rhinitis was more severe in nonallergic patients. Asthma was more
      frequent in atopic patients, whereas ASA triad was more frequent in nonatopic
      patients. Atopic patients showed higher VAS scores and worse QoL. CONCLUSION:
      Atopic NP patients showed worse QoL, higher incidence of asthma and a less severe
      form of rhinitis than non-atopic patients.

PMID- 23168145
TI  - Ultrasonographic monitoring of new expanded polytetrafluoroethylene implant
      thickness after augmentation rhinoplasty.
AB  - BACKGROUND: Expanded polytetrafluoroethylene (e-PTFE) is currently one of the
      most popular implant materials for rhinoplasty. Surgiform (Surgiform Technology,
      Ltd., Lugoff, SC) is a recently introduced ePTFE material with physical
      characteristics that are slightly different  from Gore-Tex (W.L. Gore &
      Associates, Flagstaff, AZ). Changes in Surgiform thickness after rhinoplasty are
      not well documented. METHODS: This prospective study enrolled 16 patients (12
      male and 4 female patients) who underwent primary augmentation rhinoplasty with 
      Surgiform. High-resolution ultrasonography was used to measure implant thickness
      after a mean follow-up period of 14.7 months (range, 8-21 months). RESULTS:
      Surgiform implants were easily and clearly demarcated from surrounding tissue.
      The mean thickness of inserted  implants was 2.37 +/- 0.80 mm at the rhinion and
      3.12 +/- 1.26 mm at the supratip. The follow-up thickness was 2.35 +/- 0.77 mm at
      the rhinion and 3.09 +/- 1.23 mm at the supratip. Implant thickness did not
      decrease significantly at the rhinion (p = 0.112) or the supratip  (p = 0.165).
      CONCLUSION: Ultrasonographic monitoring indicated that Surgiform e-PTFE does not
      shrink significantly over time.

PMID- 23168146
TI  - Effects of escitalopram on symptoms and quality of life in patients with allergic
      rhinitis.
AB  - BACKGROUND: Insufficient response to treatment and declining quality of life
      illustrate the continuing need to find new treatment modalities for allergic
      rhinitis (AR). The purpose of this study was to assess how escitalopram affects
      symptoms and quality of life among AR  patients. METHODS: This study included 120
      patients with AR, who were divided into four treatment groups of 30 patients
      each. Patients were assessed before treatment and at the end of the 3rd month
      based on nasal symptom scores, otorhinolaryngological examination, the
      Rhinoconjunctivitis  Quality of Life Questionnaire, and the Beck Depression and
      Anxiety Inventory. All patients received standardized treatments. Group A
      patients with positive Beck Depression and Anxiety Inventory scores received
      escitalopram, and group B patients with positive Beck Depression and Anxiety
      Inventory  scores received placebo. Group C patients with negative Beck
      Depression and Anxiety Inventory scores received escitalopram, and group D
      patients with negative Beck Depression and Anxiety Inventory scores received
      placebo. RESULTS: Anxiety scores pre- and posttreatment revealed  a statistically
      significant reduction in groups A, C, and D. All four groups exhibited reduced
      posttreatment scores for sleep, nonnasal and noneye symptoms, eye symptoms, and
      emotions. A statistically significant difference appeared between groups A and B
      in terms of general complaints and  nasal symptom scores. CONCLUSION: The
      positive effects of escitalopram on posttreatment quality of life in the Beck
      positive patient group were a predictable outcome. Otolaryngologists should pay
      more attention to the moods of their patients with AR while they evaluate 
      treatment during clinical follow-up visits.

PMID- 23168147
TI  - Advantages of glove finger-coated polyvinyl acetate pack in endoscopic sinus
      surgery.
AB  - BACKGROUND: This study investigated the efficacy of glove finger-coated polyvinyl
      acetate (PA) pack on hemostasis, pain levels, and wound healing after endoscopic
      sinus surgery (ESS). METHODS: A prospective, randomized, double-blinded
      controlled  study was performed in 30 patients who underwent bilateral ESS for
      chronic rhinosinusitis. Fifteen patients (control group) had both nasal cavities
      packed with PA pack (Merocel; Medtronic Xomed, Jacksonville, FL) and another 15
      subjects (experimental group) had their nasal cavities packed  with PA in a glove
      finger. Pain levels were assessed by patients on a visual analog scale 12 hours
      after surgery and at the time of packing removal. The amount of bleeding on
      removal were quantified by weighing it after removal. Lund-Kennedy score and
      synechiae formation were assessed at 4,  8, and 12 weeks after surgery. The use
      of analgesics and oral steroid was compared between the two groups. RESULTS: The
      experimental group showed lower levels of pain and lessened bleeding during
      packing removal than the control group. There were no differences in pain  levels
      at 12 hours after surgery, use of analgesics and oral steroid between the two
      groups. One (6%) of each group had postoperative bleeding and required additional
      packing for hemostasis. Lower Lund-Kennedy score at postoperative 4 weeks was
      documented in the experimental group. In addition,  two (13%) control subjects
      developed a synechiae between the middle turbinate and the lateral wall.
      CONCLUSION: PA packing in a glove finger is advantageous in terms of pain,
      bleeding on packing removal, and postoperative wound healing, compared with PA
      pack only.

PMID- 23168148
TI  - The role of fungi in diseases of the nose and sinuses.
AB  - BACKGROUND: Human exposure to fungal elements is inevitable, with normal
      respiration routinely depositing fungal hyphae within the nose and paranasal
      sinuses. Fungal species can cause sinonasal disease, with clinical outcomes
      ranging from mild symptoms to intracranial invasion  and death. There has been
      much debate regarding the precise role fungal species play in sinonasal disease
      and optimal treatment strategies. METHODS: A literature review of fungal diseases
      of the nose and sinuses was conducted. RESULTS: Presentation,  diagnosis, and
      current management strategies of each recognized form of fungal rhinosinusitis
      was reviewed. CONCLUSION: Each form of fungal rhinosinusitis has a characteristic
      presentation and clinical course, with the immune status of the host playing a
      critical pathophysiological  role. Accurate diagnosis and targeted treatment
      strategies are necessary to achieve optimal outcomes.

PMID- 23168149
TI  - Sensitivity of MUC5AC to topical corticosteroid is negatively associated with
      interleukin-17A in patients with allergic rhinitis.
AB  - BACKGROUND: Although Interleukin (IL)-17A has been suggested to play a role in
      corticosteroid hyporesponsiveness, whether IL-17A is able to affect the
      sensitivity of MUC5AC to intranasal corticosteroid treatment in patients with
      allergic rhinitis (AR) is unclear. METHODS: Twenty patients with moderate to
      severe AR were enrolled in this study and the expression of MUC5AC, IL-17A, and
      glucocorticoid receptor beta (GR beta) was detected using immunochemical staining
      and quantitative reverse transcription polymerase chain reaction (RT-PCR) before 
      and after treatment with fluticasone propionate (FP) nasal spray for 4 weeks,
      respectively. In addition, the effects of FP on IL-13- and IL-17A-induced MUC5AC
      and GR beta were also evaluated in the primarily cultured human nasal epithelial
      cells (HNECs) in vitro. RESULTS: The increased MUC5AC expression was associated
      with IL-17A levels in AR, and IL-17A was found to affect the inhibition of MUC5AC
      by corticosteroid treatment. Both IL-13 and IL-17A significantly promoted MUC5AC
      mRNA expression in HNECs, and FP treatment was able to significantly inhibit 
      MUC5AC mRNA expression in HNECs induced by IL-13 but not for that induced by IL
      17A. Also, IL-17A but not IL-13 promoted GR beta mRNA expression in HNECs, which
      was not affected by administration of corticosteroid. CONCLUSION: Our results
      suggest that the sensitivity of  MUC5AC to topical corticosteroid is negatively
      associated with IL-17A in AR patients. This might help us to gain more insight
      into the pathophysiology and the pharmacotherapeutic mechanisms on AR treatment.

PMID- 23168150
TI  - Squamous cell carcinoma antigen production in nasal inverted papilloma.
AB  - BACKGROUND: The clinical importance of serum squamous cell carcinoma antigen
      (SCCA) and SCCA subclasses has not been established for treating inverted
      papilloma (IP). The aim of this study was to clarify the clinical importance of
      serum SCCA and its subclasses in IP, compared  with maxillary squamous cell
      carcinoma and inflammatory disease. METHODS: Serum SCCA was measured in 22
      patients with IP (IP group), 11 with maxillary squamous cell carcinoma (carcinoma
      group), and 22 with inflammatory disease (inflammatory group). mRNA expression of
      SCCA  subclasses was examined using quantitative real-time polymerase chain
      reaction. RESULTS: In the IP group, 81.8% showed elevated serum SCCA, and 90.3%
      with recurrent IP showed elevated SCCA. The preoperative SCCA value (mean +/- SD,
      3.99 +/- 4.39) in the IP group  was significantly higher than in the carcinoma
      (1.28 +/- 0.88; p = 0.012) and inflammatory (0.60 +/- 0.31; p < 0.001) groups.
      mRNA expression of SCCA1 and SCCA2 in the IP group was higher than in the
      carcinoma and inflammatory groups. The SCCA2/SCCA1 ratio of mRNA expression (0.11
      +/- 0.06) in the IP group was similar to that (0.11 +/- 0.09) in the
      inflammatory group, although the ratio (0.20 +/- 0.12) in the carcinoma group was
      significantly higher than in the IP and inflammatory groups. The receiver
      operating characteristic curve analysis for the SCCA2/SCCA1  ratio to detect
      carcinoma yielded an area under the curve of 0.760 (95% confidence interval,
      0.626-0.894). CONCLUSION: The serum level of SCCA is effective for detecting IP,
      including recurrent IP. In contrast, the SCCA2/SCCA1 ratio is useful for
      detecting squamous  cell carcinoma among other sinonasal diseases.

PMID- 23168151
TI  - Peripheral blood and tissue T regulatory cells in chronic rhinosinusitis.
AB  - BACKGROUND: The pathogenesis of chronic rhinosinusitis (CRS) has not been fully
      elucidated. Increased inflammatory cell infiltration and decreased numbers and/or
      impaired function of T regulatory cells (Tregs) have been reported. This study
      aimed to determine the role of  Tregs in CRS in peripheral blood (PB) and sinus
      tissue. METHODS: Sinus tissue was obtained from 16 CRS subjects and 5 controls.
      PB from additional 16 CRS subjects and total 20 controls was obtained.
      Immunohistochemical analysis (CD3(+), CD4(+), CD8(+),  and Treg [CD4(+)-FoxP3(+)
      and CD25(+)-FoxP3(+)] cells) of sinus tissue was performed. Percentage of PB
      Tregs (CD4(+)-CD25(+)-FoxP3(+) cells) was analyzed by flow cytometry. Spontaneous
      and phytohemagglutinin (PHA)-induced release  of cytokines (IL-6, IL-4, IL-10,
      interferon gamma, transforming growth factor [TGF] beta1, and TNF-alpha) from PB
      mononuclear cells (PBMCs) was determined. RESULTS: PB flow cytometric analysis
      revealed a lower percentage of Tregs in subjects with CRS compared with healthy 
      controls (p = 0.0003). Although no differences in the PB Treg counts were
      observed between the CRS subjects with nasal polyposis (CRSwNP) and without nasal
      polyposis (CRSsNP), immunohistochemical analysis performed on sinus tissue
      revealed a higher proportion of Tregs in CRSwNP subjects compared  with CRSsNP (p
      < 0.05). Additionally, we failed to detect any Tregs from control sphenoid sinus
      tissue. Lower levels of regulatory cytokines (IL-10 and TGF-beta1) and higher
      levels of proinflammatory cytokines (TNF-alpha and IL-6) were found from PBMCs
      from CRS subjects compared with  controls (p < 0.05). CONCLUSION: Our findings
      suggest that CRS subjects exhibit a decreased percentage of PB Tregs compared
      with normal controls. PBMCs from CRS subjects show a more proinflammatory and
      less regulatory phenotype.

PMID- 23168152
TI  - Dysregulated survivin expression in nasal polyps of individuals with aspirin
      exacerbated respiratory disease.
AB  - BACKGROUND: A derailed balance of cell proliferation and apoptosis is presumed to
      result in cell hyperplasia as a typical feature of nasal polyps. Survivin, a
      protein of the inhibitors of the apoptosis family is proposed to promote polyp
      formation. However, studies concerning  survivin expression in chronic
      rhinosinusitis (CRS) with nasal polyps are rare and the specificity of the
      survivin expression in nasal polyps from individuals with aspirin-exacerbated
      respiratory disease (AERD) has not been investigated. METHODS:
      Immunohistochemical survivin  expression analysis was performed. Samples were
      taken from the ethmoid sinus of individuals with CRS with nasal polyps with and
      without AERD during sinus surgery and control specimens of the inferior turbinate
      from individuals without CRS. Cell cultures were stimulated with recombinant
      vascular  endothelial growth factor (VEGF(165)) and the resulting survivin
      expression was analyzed by Western blot. RESULTS: The survivin expression of 61
      specimens was analyzed by quantitative immunohistochemistry and a potential VEGF
      dependant stimulation of survivin in  cell cultures was investigated. The
      survivin expression in nasal polyps from individuals with AERD was increased
      compared with the controls (median, 1194 versus 927 arbitrary units [A.U.]; p =
      0.054). Western blot analysis revealed in vitro a VEGF-dependant regulation of
      survivin in  nasal polyps from individuals without AERD, but not in those with
      AERD (p = 0.05). CONCLUSION: Enhanced survivin expression might result in
      decreased apoptosis and cellular hyperplasia as a part of the largely unknown
      pathophysiology of nasal polyp formation. Furthermore,  we hypothesize a
      pathological, VEGF-independent constitutive survivin expression in nasal polyps
      of individuals with AERD.

PMID- 23168153
TI  - Allergic rhinitis and its impact on work productivity in primary care practice
      and a comparison with other common diseases: the Cross-sectional study to
      evAluate work Productivity in allergic Rhinitis compared with other common
      dIseases (CAPRI) study.
AB  - BACKGROUND: Allergic rhinitis (AR) is a highly prevalent allergic disease and
      also counts among the 10 most frequent reasons for medical consultation. Its
      impact on quality of life (QoL) and work productivity has been established but
      comparisons with other diseases are rare  in the literature. The aim of this
      study was to evaluate the impact of AR in health-related QoL (HRQoL) and work
      productivity in primary care patients, compared with other prevalent diseases
      such as hypertension, diabetes mellitus (DM) type II, and symptomatic depression.
      METHODS: Six hundred sixteen patients were included in a multicenter cross
      sectional observational study. A generic HRQoL questionnaire, 36-item Short Form,
      and a specific questionnaire, "Work Productivity and Activity Impairment" were
      handed out to measure QoL and work productivity  impact of the diseases. To
      assess clinical severity with a comparable scale between diseases Clinical Global
      Impression (CGI) had been used. RESULTS: Symptomatic depression was found to
      produce the greatest impairment on work productivity with a decrease of 59.5%,
      with  significant differences compared with AR, hypertension, and DM type II (p <
      0.05). Symptomatic depression was found to produce the highest negative impact on
      daily activities with a statistically significant reduction of 59.4% (p < 0.05)
      compared with AR (26.6% decrease), hypertension  (8.8% decrease), and DM (16.7%
      decrease) patients. Differences between AR and DM or hypertension were also
      significant (p < 0.05). Restriction on daily activities for AR was 27.8%, which
      is significantly higher (p < 0.05) than hypertension (19.8% decrease) but not DM
      (25.7% decrease).  Depression had the highest impairment on daily activities
      (59.4%), compared with the remaining three groups (p < 0.05). CONCLUSION: AR
      impairs work productivity in a greater magnitude than hypertension and DM type
      II.

PMID- 23168154
TI  - Effect of intranasal steroids on glucose and hemoglobin A1c levels in diabetic
      patients.
AB  - BACKGROUND: Intranasal steroids are widely used for the treatment of inflammatory
      diseases of the nose and sinuses such as rhinosinusitis, allergic rhinitis, and
      nonallergic rhinitis. Along with the general otherwise healthy population, many
      diabetic patients use intranasal  steroids as well. This study was designed to
      evaluate the adverse effects of long-term treatment with intranasal
      corticosteroid preparations in diabetic patients. METHODS: The study group
      included all diabetic patients treated with intranasal steroids for at least 3
      months  at primary care clinics in Clalit Health Services Central District in
      Israel in 2002-2007. The central database had been reviewed for demographic data,
      medical history, medications, and laboratory test results. RESULTS: A total of
      1768 diabetic patients were treated  with topical nasal steroid sprays during the
      study period. Data on hemoglobin A1c (HbA1c) levels both before and during
      steroid treatment was available for 245 patients, and data on fasting serum
      glucose levels at both time points was available for 163 patients. On statistical
      analysis, there  was no change in either measure from baseline to 3 months after
      starting treatment (p = 0.104 and p = 0.101, respectively). Treatment with
      triamcinolone acetonide was associated with a significantly greater increase in
      fasting serum glucose levels than other preparations (p = 0.006). CONCLUSION:
      Intranasal corticosteroids seem to have no adverse effects on HbA1c and serum
      glucose levels in diabetic patients. Their long-term use appears to be safe,
      provided that the patients are carefully monitored, especially those receiving
      triamcinolone acetonide.

PMID- 23168155
TI  - Microwave disinfection: assessing the risks of irrigation bottle and fluid
      contamination.
AB  - BACKGROUND: It was previously shown that 50% of irrigation bottles and 40% of
      irrigation fluids had evidence of bacterial contamination despite cleaning with
      hot water and soap. Although a novel method of microwave disinfection has
      recently been proposed to minimize contamination  risk, this has not been studied
      in a real life setting. This study investigates the effectiveness of microwave
      disinfection for reducing both nasal irrigation bottle and irrigation fluid
      contamination risk after endoscopic sinus surgery (ESS). METHODS: Twenty
      consecutive  patients underwent ESS for chronic rhinosinusitis. Patients were
      given NeilMed Sinus Rinse bottles (NeilMed Pharmaceuticals, Inc., Santa Rosa CA)
      to use twice daily, with microwave cleaning instructions preoperatively. Bottles
      were collected and cultured 1 week postoperatively. Sterile saline  (5 mL) was
      mixed into the irrigation bottle and cultured separately. An additional 10
      patients were recruited whereby the bottle was cultured at collection and
      immediately after microwave disinfection was performed in the clinic. RESULTS:
      For the first cohort of the study,  40% of the bottles and 20% of the irrigation
      samples had positive cultures 1 week postoperatively. Common bacteria included
      Acinetobacter, coagulase-negative Staphylococcus, and Gram-negative bacilli. For
      the second cohort of patients, 20% of the irrigation bottles had positive 
      cultures. However, after supervised microwave disinfection, there was a 0%
      contamination rate. CONCLUSION: Despite detailed instructions on microwave
      disinfection, positive bacterial cultures may still occur after ESS. This risk,
      however, appears to be significantly reduced  when bottles are microwaved under
      supervision. These findings suggest either a reduced patient compliance to
      cleaning or a time-dependent recontamination risk after disinfection.

PMID- 23168156
TI  - The Young's procedure for severe epistaxis from hereditary hemorrhagic
      telangiectasia.
AB  - BACKGROUND: Surgical treatment of epistaxis in hereditary hemorrhagic
      telangiectasia (HHT) has historically been managed with the laser procedure or
      the septodermoplasty procedure. For transfusion-dependent patients with severe
      epistaxis we have been performing the Young's  procedure or surgical closure of
      the nostrils. The objective of this study was to report treatment of severe
      epistaxis related to HHT with the Young's procedure and assess patient outcome.
      METHODS: Patients with severe iron or blood transfusion-dependent epistaxis  who
      underwent a Young's procedure in three otolaryngology HHT centers were reviewed.
      Patients were evaluated for postoperative epistaxis and subjective outcome.
      RESULTS: Forty-three patients underwent a Young's procedure for severe epistaxis
      and were observed for a mean  of 34 months. The procedure was well tolerated by
      all patients and 30 of 36 patients (83%) experienced complete cessation of
      bleeding after the Young's procedure. Patients had a mean increase in hemoglobin
      of 4.68 g/dL after the procedure. The average Glasgow Benefit Inventory score
      after  surgery was 43.56. No patients requested a reversal of the procedure.
      CONCLUSION: The Young's procedure is a safe and efficacious procedure with
      complete cessation of epistaxis in most patients with severe epistaxis and HHT.

PMID- 23168157
TI  - Endoscopic medial maxillectomy with preservation of inferior turbinate and
      nasolacrimal duct.
AB  - BACKGROUND: Endoscopic medial maxillectomy (EMM) is a safe and effective
      procedure for treatment of inverted papilloma (IP) originating from the maxillary
      sinus. However, EMM usually removes the inferior turbinate and nasolacrimal duct.
      The inferior turbinate has a critical  function in conditioning of the nasal
      airflow, and resection of the nasolacrimal ducts has a risk of epiphora. We
      developed a newly derived surgical technique, endoscopic modified medial
      maxillectomy (EMMM), which enables preservation of the inferior turbinate and
      nasolacrimal duct. METHODS: A retrospective case series of six patients with IP
      and nine patients with mucoceles of the maxillary sinus after a Caldwell-Luc
      operation, who underwent surgery using the EMMM technique, were reviewed.
      RESULTS: In patients with IP, there were no recurrences  for a mean follow-up of
      16.7 months. Eight of nine patients with mucoceles of the maxillary sinus showed
      patency. All patients showed preservation of the inferior turbinate. One patient
      with mucocele was referred for dacryocystorhinostomy because of epiphora.
      CONCLUSION: EMMM  produces access to the maxillary sinus identically to
      conventional EMM, despite preservation of the inferior turbinate and nasolacrimal
      duct.

PMID- 23168158
TI  - The validation of an endoscopic sinus surgery skills training model: a pilot
      study.
AB  - BACKGROUND: Performing functional endoscopic sinus surgery (FESS) requires a
      trainee surgeon to develop both thorough anatomic understanding and new manual
      dexterity skills. Traditionally, these skills were learned in the operating room
      setting. In an era of available surgical  simulation, this practice introduces
      ethical concerns about exposing patients to unnecessary risks during surgical
      skills development. Additionally, cost-effective rhinologic training has become
      increasingly important. To address these problems, a low-cost, intermediate
      fidelity FESS training  model was developed, and both speed and accuracy of task
      completion were measured to assess both immediate and intermediate-term skills
      retention. METHODS: Preliminary data were collected on 12 medical students and 10
      resident-level (PGY1, -2, and -3) learners. Distinct  tasks were performed five
      times on the initial day of testing and repeated after 2 weeks. RESULTS: Both
      groups attained statistically significant improvement in time to complete both
      tasks by the second iteration of each task and retained this effect after 2
      weeks. Similarly,  statistically significant improvement was seen for accuracy
      relative to the initial attempt by the fifth iteration for residents. This effect
      was also seen by the third through fifth iterations and after 2 weeks for
      students. Additionally, when the 2-week follow-up testing was compared with  the
      fifth attempt, the only skills that deteriorated significantly were the resident
      group with the complex task times and the students with measures of accuracy.
      However, in both cases a highly significant improvement from initial attempts was
      maintained (p = 0.02 and p = 0.005, respectively).  Residents were significantly
      faster than medical students at both simple and complex tasks for attempts 1
      through 4, but this difference was not significant for attempt 5 and after 2
      weeks. Residents had significantly fewer errors for all but the 2-week data
      point. CONCLUSION: The data from this pilot study support improved FESS skills
      for both medical students and residents using this low-cost, intermediate
      fidelity model.

PMID- 23168159
TI  - Silastic splints reduce middle meatal adhesions after endoscopic sinus surgery.
AB  - BACKGROUND: Adhesions frequently form between the middle turbinate and lateral
      nasal wall after endoscopic sinus surgery (ESS) and are a possible cause for
      surgical failure. Many absorbable and nonabsorbable spacers have been tried to
      improve healing. This study was designed  to ascertain whether placement of a
      thin silastic splint into the middle meatus after sinus surgery for 2 weeks
      reduces adhesion formation and whether a reduction in the adhesion rate improves
      patient outcomes in the early postoperative phase. METHODS: Forty-two patients 
      who were scheduled to undergo ESS for chronic rhinosinusitis were randomized to
      have a silastic splint placed into the middle meatus on one side of the nose but
      not the other at the completion of surgery. Splints were removed 2 weeks
      postoperatively. Symptom scores were recorded for each side  of the nose up to 12
      weeks after surgery and ethmoid cavities were graded at the 6- and 12-week visits
      along with assessment of adhesions. Patients were blinded to which side was
      splinted as was the surgeon assessing ethmoid cavities at 6 and 12 weeks.
      RESULTS: Thirty-three  patients completed 12 weeks of follow-up. Nasal
      obstruction and facial pain/discomfort were significantly higher on splinted
      sides for the first 2 weeks. More interventions were performed to debride
      adhesions in nonsplinted sides. Endoscopy revealed no adhesions at 12 weeks for
      sides treated  with a splint whereas 9 of 33 nonsplinted sides had persistent
      adhesions. There were no significant differences in symptom or ethmoid cavity
      scores at 6 or 12 weeks between sides treated with splints versus sides treated
      without splints or between sides with adhesions versus without adhesions.
      CONCLUSION: Middle meatal silastic splints reduce adhesions after ESS but
      increase early nasal obstruction and discomfort. Their use did not significantly
      change symptom or ethmoid cavity scores at 12 weeks.

PMID- 23168161
TI  - Response to "Replies to Fry et al. (Toxicon 2012, 60/4, 434-448). Part A.
      Analyses of squamate reptile oral glands and their products: A call for caution
      in formal assignment of terminology designating biological function".

PMID- 23168162
TI  - Molecular genetic conspecificity of Spiculopteragia houdemeri (Schwartz, 1926)
      and S. andreevae (Drozdz, 1965) (Nematoda: Ostertagiinae) from wild ruminants in
      Japan.
AB  - Male dimorphism of the subfamily Ostertagiinae (Nematoda: Trichostrongylidae) is
      a well-known phenomenon, and two or more morphotypes of a single species have
      previously been described as different species. Two Spiculopteragia spp., S.
      houdemeri (syn. S. yamashitai) and S. andreevae (syn. Rinadia andreevae) recorded
      in Asian cervids and wild bovids, are considered to represent major and minor
      morphs of S. houdemeri, respectively, based solely on their co-occurrence in the
      same host individual along with monomorphic females. In this study, males of
      morph houdemeri ( = S. houdemeri) and morph andreevae ( = S. andreevae) as well
      as females with three different vulval ornamentations were collected from sika
      deer (Cervus nippon) and Japanese serows (Capricornis crispus) distributed on the
      mainland of Japan. Morphologically characterized worms were subjected to
      molecular genetic analyses based on the internal transcribed spacer region of the
      ribosomal RNA gene and a partial region of the cytochrome c oxidase subunit I
      gene of mitochondrial DNA. Of 181 collected sika deer, 177 (97.8%) and 73 (40.3%)
      deer harboured males of morphs houdemeri and andreevae, respectively. Worm
      numbers of the former morph were found to range between 1 and 444 per individual,
      whereas only 1-25 worms per individual were detected for the latter morph. Five
      out of six serows harboured 47-71 or 2-9 males of morphs houdemeri and andreevae
      per individual, respectively. Females with one or two vulval flaps were
      predominant, but there was a substantial presence of flapless females in both
      host species. All the morphs of male and female adults had an identical genetic
      background, thus directly confirming the morphological polymorphism of S.
      houdemeri. 

PMID- 23168164
TI  - Distinct metabolic flow enables large-scale purification of mouse and human
      pluripotent stem cell-derived cardiomyocytes.
AB  - Heart disease remains a major cause of death despite advances in medical
      technology. Heart-regenerative therapy that uses pluripotent stem cells (PSCs) is
      a potentially promising strategy for patients with heart disease, but the
      inability to generate highly purified cardiomyocytes in sufficient quantities has
      been a barrier to realizing this potential. Here, we report a nongenetic method
      for mass-producing cardiomyocytes from mouse and human PSC derivatives that is
      based on the marked biochemical differences in glucose and lactate metabolism
      between cardiomyocytes and noncardiomyocytes, including undifferentiated cells.
      We cultured PSC derivatives with glucose-depleted culture medium containing
      abundant lactate and found that only cardiomyocytes survived. Using this
      approach, we obtained cardiomyocytes of up to 99% purity that did not form tumors
      after transplantation. We believe that our technological method broadens the
      range of potential applications for purified PSC-derived cardiomyocytes and could
      facilitate progress toward PSC-based cardiac regenerative therapy.

PMID- 23168165
TI  - Filtering and segmentation of 3D angiographic data: Advances based on
      mathematical morphology.
AB  - In the last 20 years, 3D angiographic imaging has proven its usefulness in the
      context of various clinical applications. However, angiographic images are
      generally difficult to analyse due to their size and the complexity of the data
      that they represent, as well as the fact that useful information is easily
      corrupted by noise and artifacts. Therefore, there is an ongoing necessity to
      provide tools facilitating their visualisation and analysis, while vessel
      segmentation from such images remains a challenging task. This article presents
      new vessel segmentation and filtering techniques, relying on recent advances in
      mathematical morphology. In particular, methodological results related to
      spatially variant mathematical morphology and connected filtering are stated, and
      included in an angiographic data processing framework. These filtering and
      segmentation methods are evaluated on real and synthetic 3D angiographic data.

PMID- 23168163
TI  - CCR2-dependent recruitment of macrophages by tumor-educated mesenchymal stromal
      cells promotes tumor development and is mimicked by TNFalpha.
AB  - Mesenchymal stromal cells (MSCs) tend to infiltrate into tumors and form a major
      component of the tumor microenvironment. These tumor-resident MSCs are known to
      affect tumor growth, but the mechanisms are largely unknown. We found that MSCs
      isolated from spontaneous lymphomas in mouse (L-MSCs) strikingly enhanced tumor
      growth in comparison to bone marrow MSCs (BM-MSCs). L-MSCs contributed to greater
      recruitment of CD11b(+)Ly6C(+) monocytes, F4/80(+) macrophages, and
      CD11b(+)Ly6G(+) neutrophils to the tumor. Depletion of monocytes/macrophages, but
      not neutrophils, completely abolished tumor promotion of L-MSCs. Furthermore, L
      MSCs expressed high levels of CCR2 ligands, and monocyte/macrophage accumulation
      and L-MSC-mediated tumor promotion were largely abolished in CCR2(-/-) mice.
      Intriguingly, TNFalpha-pretreated BM-MSCs mimicked L-MSCs in their chemokine
      production profile and ability to promote tumorigenesis of lymphoma, melanoma,
      and breast carcinoma. Therefore, our findings demonstrate that, in an
      inflammatory environment, tumor-resident MSCs promote tumor growth by recruiting
      monocytes/macrophages.

PMID- 23168166
TI  - Reliability of a novel procedure to monitor the flexibility of lower limb muscle
      groups in highly-trained adolescent athletes.
AB  - OBJECTIVES: To evaluate the reliability level of an innovative method using a
      standardized stretch force to assess the flexibility of lower limb muscle groups
      in highly-trained adolescent athletes and to examine whether interchanging the
      examiners affects the reliability of the measures. DESIGN: Randomized test-retest
      study. SETTING AND PARTICIPANTS: In ten athletes, the flexibility of eight lower
      limb muscle groups was examined on two occasions on both sides and in two phases:
      a video capture by three distinct operators and an analysis by three distinct
      analysers. The reliability of the measures was assessed by the coefficient of
      variation (CV, 90% CI). Between-analysers and between-operators standardized
      differences (i.e., Cohen's d) were calculated. RESULTS: CV (%, 90% CI) were 8.3%
      (7.5; 9.3) for quadriceps, 3.3% (3.0; 3.7) for hamstrings, 7.2% (6.5-8.0) for
      adductors, 5.7% (5.1; 6.3) for gastrocnemius, 4.5% (4.0; 5.0) for soleus, 2.6%
      (2.3; 2.9) for hip flexors, 9.6% (8.6; 10.8) for hip medial rotators and 12.4%
      (12.2; 14.0) for hip lateral rotators. There was no substantial (i.e., Cohen's d
      < 0.2) difference in CV between all the possible operators/analysers
      combinations. CONCLUSION: This method has a moderate-to-good reliability level
      and is examiner-independent. It may be implemented in future injury prevention
      programs, in order to monitor the flexibility of highly-trained adolescent
      athletes.

PMID- 23168167
TI  - Adenosine A(2A) receptor activation supports an atheroprotective cholesterol
      balance in human macrophages and endothelial cells.
AB  - The adenosine A(2A) receptor (A(2A)R) plays an important role in the regulation
      of inflammatory and immune responses. Our previous work has demonstrated that
      A(2A)R agonists exhibit atheroprotective effects by increasing expression of
      reverse cholesterol transport proteins in cultured human macrophages. This study
      explores the impact of pharmacologic activation/inhibition and gene silencing of
      A(2A)R on cholesterol homeostasis in both THP-1 human monocytes/macrophages and
      primary human aortic endothelial cells (HAEC). THP-1 human monocytes/macrophages
      and HAEC exposed to the A(2A)R-specific agonist ATL313 exhibited upregulation of
      proteins responsible for cholesterol efflux: the ABCA1 and G1 transporters.
      Further, activation of A(2A)R led to upregulation of the cholesterol metabolizing
      enzyme P450 27-hydroxylase, accompanied by intracellular changes in level of
      oxysterols. We demonstrate that anti-atherogenic properties of A(2A)R activation
      are not limited to the regulation of lipid efflux in vasculature, but include
      protection from lipid overload in macrophages, particularly via suppression of
      the CD36 scavenger receptor. The reduced lipid accumulation manifests directly as
      a diminution in foam cell transformation. In THP-1 macrophages, either A(2A)R
      pharmacological blockade or gene silencing promote lipid accumulation and enhance
      foam cell transformation. Our pre-clinical data provides evidence suggesting that
      A(2A)R stimulation by ATL313 has the potential to be a viable therapeutic
      strategy for cardiovascular disease prevention, particularly in patients with
      elevated risk due to immune/inflammatory disorders.

PMID- 23168168
TI  - KIF19A is a microtubule-depolymerizing kinesin for ciliary length control.
AB  - Cilia control homeostasis of the mammalian body by generating fluid flow. It has
      long been assumed that ciliary length-control mechanisms are essential for proper
      flow generation, because fluid flow generation is a function of ciliary length.
      However, the molecular mechanisms of ciliary length control in mammals remain
      elusive. Here, we suggest that KIF19A, a member of the kinesin superfamily,
      regulates ciliary length by depolymerizing microtubules at the tips of cilia.
      Kif19a(-/-) mice displayed hydrocephalus and female infertility phenotypes due to
      abnormally elongated cilia that cannot generate proper fluid flow. KIF19A
      localized to cilia tips, and recombinant KIF19A controlled the length of
      microtubules polymerized from axonemes in vitro. KIF19A had ATP-dependent
      microtubule-depolymerizing activity mainly at the plus end of microtubules. Our
      results indicated a molecular mechanism of ciliary length regulation in mammals,
      which plays an important role in the maintenance of the mammalian body.

PMID- 23168169
TI  - Regenerative neurogenesis from neural progenitor cells requires injury-induced
      expression of Gata3.
AB  - The adult zebrafish brain, unlike mammalian counterparts, can regenerate after
      injury owing to the neurogenic capacity of stem cells with radial glial
      character. We hypothesized that injury-induced regenerative programs might be
      turned on after injury in zebrafish brain and enable regenerative neurogenesis.
      Here we identify one such gene-the transcription factor gata3-which is expressed
      only after injury in different zebrafish organs. Gata3 is required for reactive
      proliferation of radial glia cells, subsequent regenerative neurogenesis, and
      migration of the newborn neurons. We found that these regeneration-specific roles
      of Gata3 are dependent on the injury because Gata3 overexpression in the
      unlesioned adult zebrafish brain is not sufficient to induce neurogenesis. Thus,
      gata3 acts as a specific injury-induced proregenerative factor that is essential
      for the regenerative capacity in vertebrates.

PMID- 23168170
TI  - The use of typing methods and infection prevention measures to control a bullous
      impetigo outbreak on a neonatal ward.
AB  - BACKGROUND: We describe an outbreak of Bullous Impetigo (BI), caused by a
      (methicillin susceptible, fusidic acid resistant) Staphylococcus aureus (SA)
      strain, spa-type t408, at the neonatal and gynaecology ward of the Jeroen Bosch
      hospital in the Netherlands, from March-November 2011. METHODS: We performed an
      outbreak investigation with revision of the hygienic protocols, MSSA colonization
      surveillance and environmental sampling for MSSA including detailed typing of SA
      isolates. Spa typing was performed to discriminate between the SA isolates. In
      addition, Raman-typing was performed on all t408 isolates. RESULTS: Nineteen
      cases of BI were confirmed by SA positive cultures. A cluster of nine neonates
      and three health care workers (HCW) with SA t408 was detected. These strains were
      MecA-, PVL-, Exfoliative Toxin (ET)A-, ETB+, ETAD-, fusidic acid-resistant and
      methicillin susceptible. Eight out of nine neonates and two out of three HCW t408
      strains yielded a similar Raman type. Positive t408 HCW were treated and
      infection control procedures were reinforced. These measures stopped the
      outbreak. CONCLUSIONS: We conclude that treatment of patients and HCW carrying a
      predominant SA t408, and re-implementing and emphasising hygienic measures were
      effective to control the outbreak of SA t408 among neonates.

PMID- 23168171
TI  - ZNF512B gene is a prognostic factor in patients with amyotrophic lateral
      sclerosis.
AB  - Recently, Iida et al. discovered a new single-nucleotide polymorphism (SNP) in
      the ZNF512B gene associated with susceptibility to amyotrophic lateral sclerosis
      (ALS). The ZNF512B gene was found to be a transcription factor promoting the
      expression of a downstream gene in the signal transduction pathway of the
      transforming growth factor-beta (TGF-beta), which is essential for the protection
      and survival of neurons but the influence of the new SNP (rs2275294) in actual
      ALS patients remained unknown. The objective of our study was to examine whether
      the new SNP in the ZNF512B gene might influence the phenotype of ALS. We
      conducted a retrospective analysis of the ZNF512B gene in 176 patients diagnosed
      as having ALS at our hospital. Evaluation of the prognosis after the onset using
      Kaplan-Meier survival curves in patients with versus without the risk allele (C
      allele: CC and CT genotypes) revealed a significantly lower survival probability
      in those with the risk allele (log-rank test, P<0.01), independent of the other
      prognostic factors in ALS. Our study revealed the influence of the new SNP in
      actual ALS patients. It would be clinically reasonable to suggest that the
      ZNF512B gene is a new prognostic factor in ALS. This study is the first, as per
      our knowledge, to indicate that the association between the new susceptibility
      gene for ALS and its pathway could be identified.

PMID- 23168172
TI  - The effect of at-birth vitamin A supplementation on differential leucocyte counts
      and in vitro cytokine production: an immunological study nested within a
      randomised trial in Guinea-Bissau.
AB  - Vitamin A supplementation (VAS) at birth was not associated with improved
      survival in a randomised, placebo-controlled trial in Guinea-Bissau. However, a
      negative sex-differential effect, which became evident after diphtheria-tetanus
      pertussis (DTP) vaccination, was noted; among girls who had received DTP, VAS at
      birth was associated with two-fold higher mortality than placebo. The objective
      of the present study was to investigate the immunological effects of VAS at birth
      within a subgroup of participants in the randomised trial. Guided by the
      mortality results, we further explored whether VAS had a differential effect
      according to sex and DTP status. At 6 weeks after randomisation and
      supplementation, we measured differential leucocyte counts and TNF-alpha,
      interferon-gamma, IL-10, IL-13 and IL-5 production in a whole-blood culture
      assay. A total of 471 children were included. VAS compared with placebo at birth
      was associated with a higher proportion of monocytes (relative risk ratio 1.26,
      95 % CI 1.07, 1.49, P=0.04), while spontaneous TNF-alpha production was lower in
      the VAS group (geometric mean ratio 0.54, 95 % CI, 0.37, 0.78, P=0.001).
      Stratified analysis showed that VAS was associated with lower TNF-alpha and IL-10
      production for girls without DTP and boys with DTP, resulting in significant
      three-way interactions between VAS, sex and DTP vaccination status (P=0.03 and
      P=0.04, respectively) for spontaneous TNF-alpha and IL-10 production. The results
      substantiate the potential role of VAS as an immunomodulatory intervention, which
      has different effects depending on concomitant health interventions and the sex
      of the recipient.

PMID- 23168173
TI  - Validated gene targets associated with curatively treated advanced serous ovarian
      carcinoma.
AB  - OBJECTIVES: High-grade serous ovarian cancer (HGSOC) mostly presents at an
      advanced stage and has a low overall survival rate. However, a subgroup of
      patients are seemingly cured after standard initial therapy. We hypothesize that
      the molecular profiles of these patients vary from long-term survivors who recur.
      METHODS: Patients with advanced HGSOC who underwent primary cytoreductive surgery
      and platinum-based chemotherapy were identified from The Cancer Genome Atlas
      (TCGA) and institutional (MSKCC) samples. A curative-intent group was defined by
      recurrence-free survival of >5years. A long-term recurrent group was composed of
      patients who recurred but survived >5years. RNA was hybridized to Affymetrix
      U133A transcription microarrays. The NanoString nCounter gene expression system
      was used for validation in an independent patient population. RESULTS: In 30
      curative and 84 recurrent patients, class comparison identified twice as many
      differentially expressed probes between the groups than expected by chance alone.
      TCGA and MSKCC data sets had 19 overlapping genes. Pathway analyses identified
      over-represented networks that included nuclear factor kappa B (NFkB)
      transcription and extracellular signal-regulated kinase (ERK) signaling. External
      validation was performed in an independent population of 28 curative and 38
      recurrent patients. Three genes (CYP4B1, CEPT1, CHMP4A) in common between our
      original data sets remained differentially expressed in the external validation
      data. CONCLUSIONS: There are distinct transcriptional elements in HGSOC from
      patients likely to be cured by standard primary therapy. Three genes have
      withstood rigorous validation and are plausible targets for further study, which
      may provide insight into molecular features associated with long-term survival
      and chemotherapy resistance mechanisms.

PMID- 23168174
TI  - Evaluation of therapeutic care delay among Latina- and European-American cervical
      cancer survivors.
AB  - OBJECTIVES: Cervical cancer (CCA) ranks among the deadliest of cancers. Globally
      CCA claims 275,000 lives yearly. Severe delays, in cancer diagnostic or
      therapeutic care, that approach >= 60 days negatively affect survival and
      survivorship outcomes. This study investigated socioeconomic and healthcare
      system factors influencing therapeutic care delays among cervical cancer
      survivors (CCS). METHODS: 291 CCS (132 European-, 50 English-proficient (EP)
      Latina- and 109 limited English-proficient (LEP) Latina-Americans) were recruited
      from cancer registries. CCS retrospectively noted the days of delay in obtaining
      therapeutic care and reasons for delays. RESULTS: CCS who were LEP Latina
      Americans, had lower income and education reported severe therapeutic delays (>=
      60 days). LEP Latina-Americans experienced delays due to financial issues,
      doctor's delay, and healthcare system issues (p < 0.001). Doctor and healthcare
      system delays significantly influenced therapeutic care delay in the logistic
      regression model. CONCLUSIONS: Healthcare system delays are primary contributors
      to ethnic differences in access to appropriately-timed care observed in this
      study. Healthcare professionals need to develop a fuller appreciation of the
      multilevel factors that contribute to healthcare barriers to better inform
      effective interventions to increase access to life saving care.

PMID- 23168175
TI  - Mutations of the TP53 gene in adenocarcinoma and squamous cell carcinoma of the
      cervix: a systematic review.
AB  - OBJECTIVE: Mutations of the tumor suppressor gene TP53 are the most significant
      events in several human cancers. Few studies have analyzed the frequency of TP53
      alterations in squamous cell carcinoma and adenocarcinoma of the cervix with
      controversial results. This study provides a detailed analysis of TP53 mutation
      spectra in cervical squamous cell carcinoma and adenocarcinoma from different
      geographical regions. METHODS: The analysis of TP53 mutational profiles was
      performed in 1353 cervical cancers retrieved from the IARC p53 mutation database
      (R15, 2010) and the COSMIC data along with the literature review of related
      studies identified by PubMed searching. RESULTS: This analysis showed a
      significant higher mutation frequency of TP53 gene in cervical adenocarcinoma (32
      of 241; 13.3%) compared to squamous cell carcinoma (39 of 657; 5.9%; P=0.0003,
      chi(2) test). The proportion of adenocarcinoma with mutated TP53 varied from 4%
      in North America to 19% in Asia. Among the six hot-spot codons of TP53 gene,
      three codons (175, 248 and 273) were the most commonly mutated in both types of
      cervical cancer, one codon (249) mainly in squamous cell carcinoma and one codon
      (282) only in adenocarcinoma. The G to A and C to T transitions were the
      prevalent type of mutations in both squamous cell carcinoma and adenocarcinoma
      (48.7% and 53.5% of all mutations, respectively). The frequency of C to A
      transversion was relatively high only in adenocarcinoma (25%), while the mirror
      mutation G to T was comparatively frequent in squamous cell carcinoma (14.6%).
      CONCLUSIONS: Different patterns of TP53 mutations occur in squamous cell
      carcinoma and adenocarcinoma of the cervix in different regions of the world. The
      highest frequency of mutated TP53 has been observed in cervical adenocarcinoma
      from Asia. Further studies are needed to better define the role of TP53
      alterations in cervical cancer and possibly to understand the impact of mutations
      on cancer prognosis and outcomes.

PMID- 23168176
TI  - Navitoclax augments the activity of carboplatin and paclitaxel combinations in
      ovarian cancer cells.
AB  - OBJECTIVES: To evaluate the efficacy of combination of navitoclax, carboplatin
      and paclitaxel in ovarian cancer. METHODS: 8 ovarian cancer cell lines were
      treated with either doublet or triplet combinations of navitoclax, carboplatin
      and paclitaxel. Interactions were assessed by determining a combination index or
      measuring caspase activity. The effect of the combinations was also evaluated by
      measuring the inhibition of cells grown as spheroids. RESULTS: Navitoclax
      exhibited modest (IC(50)=3-8 MUM) single agent potency. Antagonism between
      carboplatin and paclitaxel was evident in Ovcar-4, Ovcar-8 and Skov-3 cells. Drug
      combinations including navitoclax with carboplatin and/or paclitaxel showed
      significantly less antagonism, or even synergy, in several cell lines than
      carboplatin/paclitaxel alone. Navitoclax enhanced the activation of caspase 3/7
      induced by carboplatin and/or paclitaxel in Igrov-1 cells. Combinations of
      navitoclax, carboplatin and paclitaxel showed more than additive activity against
      Igrov-1 spheroids. CONCLUSIONS: Navitoclax improves the activity of combinations
      of carboplatin and paclitaxel in vitro. Our observations, taken with other
      published data, provide a rationale for clinical trials of navitoclax in ovarian
      cancer in combination with chemotherapy.

PMID- 23168177
TI  - Effects of child and adolescent health on educational progress.
AB  - Understanding how childhood and adolescent health may affect schooling is
      important for understanding the socioeconomic ramifications of poor early-life
      health as well as the relations between schooling and adult health. Using three
      waves of U.S. longitudinal data with extensive covariate information on a
      national sample of 2368 American children aged 5-14 at baseline, we used
      regression methods to investigate how patterns of general health status over a 10
      year period relate to completed years of schooling at the end of follow-up. As a
      sensitivity analysis, we used sibling fixed effects models to help control for
      differences stemming from familial or community factors shared between siblings.
      The effect of health on years of completed schooling appeared to accumulate over
      time, and was more evident among children who were older at baseline. Among
      participants aged 5-7, 8-10, and 11-14 at baseline, average differences in years
      of completed schooling between participants with poor health in all 3 waves and
      those with good health in all 3 waves were 0.02 ([95% confidence interval] -0.31,
      0.35), -0.50 (-0.88, -0.12), and -1.28 (-1.78, -0.78), respectively. Point
      estimates from fixed effects models were very similar. Our results document the
      emergence and compounding over time of health-related disparities in schooling at
      young ages, suggesting a vicious cycle between poor health and educational
      outcomes. Future research better characterizing how early-life health affects
      educational progress will ultimately be necessary for developing effective
      interventions to reduce educational and health disparities.

PMID- 23168178
TI  - Self-management education approach: engaging patients in creating a personal and
      relevant action plan (part 2): I keep telling patients what to do, so why don't
      they make progress?

PMID- 23168179
TI  - MR imaging of normal hip anatomy.
AB  - Understanding normal anatomy of the hip is important for diagnosing its
      pathology. MR arthrography is more sensitive for the detection of intra-articular
      pathology than noncontrast MR imaging. Important elements of the osseous
      structures on MR imaging include the alignment and the marrow. Acetabular
      ossicles may be present. Normal variations involving the cartilage include the
      supra-acetabular fossa and the stellate lesion. Important muscles of the hip are
      the sartorius, rectus femoris, iliopsoas, gluteus minimus and medius, adductors,
      and hamstrings. The iliofemoral, ischiofemoral, and pubofemoral ligaments
      represent thickenings of the joint capsule that reinforce and stabilize the hip
      joint. Normal variations in the labrum include labral sulcus and absent labrum.
      The largest nerves in the hip and thigh are the sciatic nerve, the femoral nerve,
      and the obturator nerve.

PMID- 23168180
TI  - Acetabular labrum.
AB  - Acetabular labral tears are a mechanical cause of hip pain. Hip MR imaging should
      be performed on 1.5-T or 3-T magnets using small field-of-view and high
      resolution imaging. The following should be used in the assessment for labral
      tear abnormalities on MR arthrography: labral morphology and contrast extension
      into the labral substance or between the labral base and acetabulum. Description
      of the labral tear and extent of tear is useful for hip arthroscopists.
      Understanding the pitfalls around the acetabular labral complex helps avoids
      misinterpretation of labral tears.

PMID- 23168181
TI  - Novel cartilage imaging techniques for hip disorders.
AB  - Hip deformity such as acetabular dysplasia and cam and pincer deformities are
      thought to be a major cause of hip osteoarthritis. Currently, clinically
      effective surgical procedures such as pelvic osteotomies and femoral and
      acetabular osteoplasties are available to correct the underlying deformity. These
      procedures are most effective in the presence of minimal chondral damage in the
      joint. Currently, and more so in the future, high-resolution morphologic imaging
      and biochemical imaging techniques such as Delayed gadolinium-enhanced MR imaging
      of cartilage, T2, and T1rho will have a clinically important role in diagnosing
      and staging chondral damage in the hip.

PMID- 23168182
TI  - Femoroacetabular impingement.
AB  - Femoroacetabular impingement (FAI) is a common cause of early-onset
      osteoarthritis of the hip. It can be caused by morphologic abnormalities
      involving the proximal femur or acetabulum, leading to abnormal abutment of the
      femoral head-neck against the acetabular rim. This repetitive trauma causes
      mechanical wear of the labrum and articular cartilage, leading to osteoarthritis
      of the hip. Magnetic resonance imaging is an accurate noninvasive imaging
      modality that can detect acetabular labral lesions and adjacent cartilage damage,
      and is able to detect underlying subtle anatomic variations of the femoral head
      neck junction and acetabulum associated with FAI.

PMID- 23168183
TI  - Ischiofemoral impingement.
AB  - Ischiofemoral impingement is a syndrome defined by hip pain associated with
      narrowing of the space between ischial tuberosity and lesser trochanter. This
      phenomenon leads to abnormalities of the quadratus femoris muscle, ranging from
      deformity and edema to tears and atrophy. This review article presents an up-to
      date discussion and imaging findings of ischiofemoral impingement, along with its
      related anatomy, clinical presentation, differential diagnosis and treatment.

PMID- 23168184
TI  - Tendon injuries of the hip.
AB  - Hip pain is a common but potentially vexing clinical problem; symptoms may be
      protean, referred, and poorly localized. History and physical examination can be
      unreliable in discriminating between intra-articular and extra-articular origins
      of pain. MR imaging augments clinical evaluation by providing information about
      the hip joint as well as the periarticular structures, which can be a source of
      symptoms. This article presents an anatomy-based review of common and less common
      tendon pathologies on MR imaging, which are considered in the differential
      diagnosis of hip pain.

PMID- 23168185
TI  - Magnetic resonance imaging of athletic pubalgia and the sports hernia: current
      understanding and practice.
AB  - Magnetic resonance imaging (MRI) has become the standard imaging modality for
      activity-related groin pain. Lesions, including rectus abdominis/adductor
      aponeurosis injury and osteitis pubis, can be accurately identified and
      delineated in patients with clinical conditions termed athletic pubalgia, core
      injury, and sports hernia. A dedicated noncontrast athletic pubalgia MRI protocol
      is easy to implement and should be available at musculoskeletal MR imaging
      centers. This article will review pubic anatomy, imaging considerations, specific
      lesions, and common MRI findings encountered in the setting of musculoskeletal
      groin pain.

PMID- 23168186
TI  - MR imaging of osseous lesions of the hip.
AB  - MR imaging, because of its multiplanar capability and superior soft tissue
      contrast resolution, is the preferred modality to assess osseous and soft tissue
      structures around the hip joint. This article reviews the clinical presentation,
      disease process, and imaging findings of important congenital and acquired
      osseous disorders of the pediatric and adult hip.

PMID- 23168187
TI  - MR imaging of hip infection and inflammation.
AB  - Inflammation of the hip may be due to infectious and noninfectious causes.
      Furthermore, involvement is categorized based on the origin and spread to
      adjacent structures involving the soft tissues, the joint, and underlying bone to
      refine the differential diagnosis. Magnetic resonance (MR) imaging is highly
      effective in establishing the presence and underlying cause of inflammatory and
      degenerative arthropathies. This article discusses the use of MR imaging for
      evaluation of various inflammatory conditions of the hip, both infectious and
      noninfectious. The number of hip prostheses is increasing, and inflammatory
      conditions involving the postoperative hip is also detailed separately.

PMID- 23168188
TI  - Magnetic resonance imaging of hip tumors.
AB  - After initial evaluation with radiography, magnetic resonance (MR) imaging is the
      most common modality used to establish the diagnosis and characterize osseous and
      soft tissue tumors of the hip. Tumors involving the proximal femur are often
      benign, and MR imaging can be specific in diagnosing solitary bone cyst,
      osteochondroma, and chondroblastoma. Benign and malignant soft tissue tumors
      about the hip are often nonspecific in their MR imaging appearances, but
      knowledge of the patient's age may direct a more limited differential diagnosis.
      In the setting of malignancy, MR imaging is commonly used to stage tumors and
      follow patients postoperatively.

PMID- 23168189
TI  - MR imaging of metal-on-metal hip prostheses.
AB  - Metal-on-metal (MoM) hip arthroplasty was expected to provide benefits over metal
      on-polyethylene systems. After widespread placement of MoM implants, outcomes
      have been disappointing. MoM implants are associated with higher serum levels of
      metal ions, adverse periarticular soft tissue reactions, and increased long-term
      failure rates. In light of these findings, it is crucial that patients with MoM
      implants be closely monitored for adverse effects. MR imaging is ideally suited
      for assessment of these patients and complements standard clinical evaluation and
      laboratory testing. This article reviews the background of MoM implants, emerging
      data on complications, strategies for using MR imaging, and MR imaging findings
      in patients with reaction to metal.

PMID- 23168190
TI  - MR imaging of the hip: pathologies and morphologies of the hip joint, what the
      surgeon wants to know.
AB  - MR imaging of the hip is frequently used in symptomatic patients before hip
      preservation surgery; it is used as a decision-making tool and as a planning
      tool. The MRI can confirm the preliminary working diagnosis, identify other
      possible sources of pain, and highlight anatomic areas that are not routinely
      viewed during surgery. In addition, MR imaging is capable of illustrating normal
      and abnormal bony morphology of the femur and pelvis; and in the case that
      arthrography is used, diagnostic injection can be administrated concurrently.
      This article highlights a surgeon's perspective on the use of MR imaging in the
      patient with nonarthritic hip pain.

PMID- 23168191
TI  - MR imaging and ultrasound correlation of hip pathologic conditions.
AB  - Magnetic resonance (MR) imaging has become the workhorse in the imaging
      evaluation of the painful or clinically abnormal hip. It provides an excellent
      anatomic overview and demonstration of the bony structures, articular surfaces,
      and surrounding soft tissues. Conversely, sonography can also demonstrate
      superficial intraarticular structures and the periarticular soft tissues, is
      quickly performed, allows dynamic evaluation of tendons and muscles, and can
      guide percutaneous procedures. These two modalities are complementary, and this
      article concentrates on the MR imaging-sonographic correlations of several
      entities about the hip.

PMID- 23168192
TI  - Magnetic Resonance Imaging Clinics of North America. Imaging of the hip.
      Foreword.

PMID- 23168193
TI  - Magnetic Resonance Imaging Clinics of North America. Imaging of the hip. Preface.

PMID- 23168195
TI  - [A perception of cardio-circulatory dysfunction in critical conditions].

PMID- 23168196
TI  - [Urine cardiac specific microRNA-1 level in patients with ST segment elevation
      acute myocardial infarction].
AB  - OBJECTIVE: To observe the change of urine level of cardiac specific microRNA-1
      (miR-1) in patients with ST segment elevation acute myocardial infarction
      (STEAMI) and investigate its potential applications. METHODS: Urine samples were
      collected from 20 STEAMI patients within 12 hours after STEAMI and from 20
      healthy volunteers as control. Urine miR-1 concentrations were measured with real
      time quantity reverse transcription-polymerase chain reaction (qRT-PCR), at the
      same time serum cardiac troponin I (cTnI) and MB isoenzyme of creatine kinase (CK
      MB) concentrations were measured. RESULTS: Serum level of cTnI, CK-MB and urine
      level of miR-1 in STEAMI patients were obviously higher than those in healthy
      control group [cTnI in blood: 19.27+/-7.53 MUg/L vs. 0.02+/-0.01 MUg/L, CK-MB in
      blood: 93.82+/-12.30 MUg/L vs. 0.86+/-0.63 MUg/L, miR-1 in urine (Ct value):
      45.50+/-4.21 vs. 52.63+/-4.41, P<0.05 or P<0.01]. The urine miR-1 level in
      patients with STEAMI had a strong correlation with serum CK-MB or cTnI when CK-MB
      < 300 MUg/L and cTnI <50 MUg/L (Ct value of urine miR-1 with blood CK-MB: r=
      0.81, P<0.01; Ct value of urine miR-1 with blood cTnI: r=-0.63, P<0.05).
      CONCLUSIONS: The results suggest that urine miR-1 could be a novel sensitive
      biomarker the early diagnosis of SETAMI.

PMID- 23168197
TI  - [The research of establishing discriminant function for patients with angina
      pectoris by stepwise analysis based on serum inflammatory factors].
AB  - OBJECTIVE: To improve cost-efficiency, discriminant functions in stepwise method
      was founded for the differential diagnosis of angina pectoris by detecting the
      serum level of high-sensitivity C-reactive protein (hs-CRP), macrophage migration
      inhibitory factor (MIF), interleukin-4 (IL-4) and interleukin-10 (IL-10) in
      patients with stable angina pectoris (SAP) and unstable angina pectoris (UAP).
      METHODS: Thirty-nine SAP patients and 47 UAP patients were enrolled into the
      study, while 39 healthy volunteers were enrolled into the controlled group
      forming the entire set of training samples. The serum levels of hs-CRP, MIF, IL-4
      and IL-10 were measured by enzyme linked immunosorbent assay (ELISA). Data was
      analyzed by software to define discriminant functions in the ways of "entering"
      and "stepwise". Both functions were evaluated by the results of validation.
      RESULTS: By the way of "enter independent together", the following discriminant
      functions were defined based on the data of training samples' age, hs-CRP, MIF,
      IL-4, IL-10: healthy control group =-129.858 + 2.869*age -2.451*hs-CRP +
      1.393*MIF + 6.001*IL-4 + 4.848*IL-10; SAP  group=-161.037 + 2.896*age-2.022*hs
      CRP + 1.662*MIF + 6.703*IL-4 + 6.287*IL-10; UAP group=-199.087 + 2.468*age
      1.440*hs-CRP + 3.404*MIF-13.875*IL-4 + 7.752*IL-10. Retrospective validation
      showed 4.8% of total miss-grouping, while cross-validation showed 5.6% of total
      miss-grouping. By the way of "stepwise", the above data was screened by software
      and  training  samples'  age, MIF and IL-10 were suggested to define the
      following functions: healthy control group = - 125.218 + 2.659 * age + 0.599*MIF
      + 5.040 * IL-10;  SAP  group=-157.864 + 2.721*age + 1.008*MIF + 6.468*IL-10; UAP
      group=- 197.327 + 2.360*age + 2.932*MIF + 7.640*IL-10. Both retrospective and
      cross validation showed 6.4% of total miss-grouping. Both sets of discriminant
      functions had the same efficiency (100%) for differential diagnosis of SAP and
      UAP. CONCLUSION: The discriminant functions based on samples' age, MIF and IL-10,
      which were screened and suggested by stepwise method, may contribute to the
      differential diagnosis of atypical SAP and UAP, and therefore demonstrate better
      cost-efficiency.

PMID- 23168198
TI  - [Changes in cardiac specific microRNA-208a level in peripheral blood in ST
      segment elevation acute myocardial infarction patients].
AB  - OBJECTIVE: To observe serum cardiac specific microRNA-208a (miR-208a) levels in
      ST segment elevation acute myocardial infarction (STEAMI) patients, and to
      explore the role of serum miR-208a levels in the diagnosis of STEAMI. METHODS:
      The serum miR-208a concentrations were assessed within 12 hours after STEAMI,
      while 30 healthy individuals as control. Serum miR-208a concentrations were
      measured with real-time quantity reverse transcription-polymerase chain reaction
      (qRT-PCR), and serum cardiac troponin I (cTnI) or MB isoenzyme of creatine kinase
      (CK-MB) concentrations were measured with enzyme linked immunosorbent assay
      (ELISA). RESULTS: The contents of serum cTnI or CK-MB in STEAMI patients were
      significantly higher than those in healthy individuals (cTnI: 17.72+/-8.43 MUg/L
      vs. 0.05+/-0.01 MUg/L, CK-MB: 250.83+/-177.26 MUg/L vs. 71.20+/-20.50 MUg/L, both
      P<0.01). Serum miR-208a concentrations were detected in all individuals with
      STEAMI within 60 PCR cycle (0-6 hours: 44.95+/-4.77, 6-12 hours: 43.98+/-4.68),
      but were beyond detection for all individuals in the healthy control group. The
      serum miR-208a relative levels in STEAMI patients were at least more than 215
      fold than that in healthy persons, compared with qRT-PCR (Ct=60) of miR-208a in
      healthy control persons (P<0.01). CONCLUSION: Serum miR-208a may be a new
      biomarker the early diagnosis of STEAMI patients.

PMID- 23168199
TI  - [Evaluation of circulating microRNA-92a for endothelial damage induced by
      percutaneous coronary intervention].
AB  - OBJECTIVE: To explore the role of microRNA-92a (miR-92a) in evaluating
      endothelium damage induced by percutaneous coronary intervention (PCI). METHODS:
      A case control study was prospectively conducted. Fifty-eight patients with ST
      segment elevation acute myocardial infarction (STEAMI) received PCI were
      enrolled. MiR-92a expression in circulation was determined on the next day after
      PCI (reverse transcription-polymerase chain reaction). The correlation between
      miR-92a expression in circulation and PCI influence factors, such as inflation
      pressure, duration of balloon inflation and length of culprit atheromatous plaque
      were explored. RESULTS: MiR-92a was lower in inflation pressure 11-19 atm (1
      atm=101.325 kPa) group [n=43, mean -0.36, 95% confidence interval (95%CI) -0.60
      to -0.12] than inflation pressure <=10 atm group (n=11, mean 1.16, 95%CI 0.80 to
      1.52, P<0.01) and >= 20 atm group (n=4, mean 0.26, 95%CI 0.26 to 0.26, P=0.1);
      and also lower in duration of balloon inflation 6-7 seconds group (n=24, mean 
      0.42, 95%CI -0.83 to -0.01) than in duration of balloon inflation <= 5 seconds
      group (n=9, mean 0.63, 95%CI 0.49 to 0.78, P=0.03) and >= 8 seconds group (n=25,
      mean 0.45, 95%CI 0.10 to 0.80, P<0.001); lower in implanted stent length <=30 mm
      (n=31, mean -0.48, 95%CI -0.80 to -0.16) than those >30 mm (n=27, mean 0.16,
      95%CI 0.01 to 0.32, P<0.01). A significantly negative correlation was found
      between inflation pressure and duration of balloon inflation. (r=-0.48, P<0.001).
      CONCLUSIONS: There is a relationship between circulating miR-92a, inflation
      pressure and duration of balloon inflation. Circulating miR-92a could be used to
      evaluate the endothelium injury induced by PCI, and be used as a new target of
      prevention and treatment of endothelial dysfunction following revascularization.

PMID- 23168200
TI  - [The predictive values of D-dimer for the early prognosis of the acute myocardial
      infarction (AMI): a review of 3134 AMI patients].
AB  - OBJECTIVE: To investigate whether D-dimer could be an early warning signal for
      patients with acute myocardial infarction (AMI), then may be helpful in risk
      assessment in emergency department. METHODS: Three thousand one hundred and
      thirty-four emergency AMI cases admitted to the hospital from January 1, 2009 to
      December 31, 2010 were retrospectively reviewed, and their age, gender, past
      medical history, D-dimer, MB isoenzyme of creatine kinase (CK-MB), cardiac
      troponin I (cTnI), the precursor of the N-terminal pro-brain natriuretic peptide
      (NT-proBNP), electrocardiogram (ECG) before treatment, and the CK-MB, cTnI and
      echocardiography left ventricular ejection fraction (LVEF) 2 hours after the
      treatment of percutaneous coronary intervention (PCI) or thrombolytic drugs,
      whether died and time from onset to death were recorded. According to the results
      of multivariate logistic regression analysis, draw the receiver operating
      characteristic curve (ROC curve) and fitting curve, and analyzed the relativity
      between the D-dimer before the treatment and prognosis of myocardial infarction.
      RESULTS: Multivariate logistic regression analysis showed that age [odds ratio
      (OR)=1.109, 95% confidence interval (95%CI) 1.073 to 1.147, P=0.000], whether
      undergoing emergency PCI (OR=4.162, 95%CI 1.980 to 8.748, P=0.000), D-dimer
      before treatment (OR=1.001, 95%CI 1.000 to 1.002, P=0.001), the LVEF values
      (OR=0.946, 95%CI 0.928 to 0.964, P=0.000) and cTnI after 2 hours of treatment
      (OR=1.011, 95%CI 1.004 to 1.018, P=0.002) were correlated to 28-day death. The
      ROC curves showed that age [area under curve (AUC) 0.796, P=0.000], whether
      undergoing emergency PCI (AUC 0.704, P=0.000), D-dimer before treatment (AUC
      0.797, P=0.000) were positively correlated with the 28-day death; the LVEF values
      (AUC 0.261, P=0.000) were negative correlated with the 28-day death. The fitting
      curve of D-dimer before treatment, the time from onset to death and the LVEF
      showed no linear correlation. CONCLUSIONS: D-dimer was correlated with the early
      prognosis of patients with myocardial infarction, but was not correlated with the
      time from onset to death. The rise in D-dimer at the early stage of AMI may be
      helpful to indicate the critical condition of the AMI patients.

PMID- 23168201
TI  - [Correlation between osteoprotegerin gene 209G/A, 245T/G and 1181G/C polymorphism
      and acute coronary syndromes in Han people of Fujian area].
AB  - OBJECTIVE: To explore the association of osteoprotegerin (OPG) gene polymorphisms
      209G/A, 245T/G and 1181G/C in the Han population of Fujian province with acute
      coronary syndrome (ACS) and its severity. METHODS: A prospective study was
      conducted. Two hundred and fifty-two cases without sibship of Fujian Han people
      was enrolled from July 2010 to September 2011, in which 68 healthy subjects as
      controls. One hundred and eighty-four patients with ACS were divided into three
      groups, 60 had one-vessel, 68 had two-vessel, and 54 had three-vessel lesion, 2
      had not been found stenosis. DNA was extracted from venous blood, different
      groups of OPG gene polymorphism was identified by Sanger Method. OPG 209G/A,
      245T/G and 1181G/C genotype frequencies and allelic frequencies were analyzed
      between ACS subjects and normal subjects and among the three groups of ACS, and
      the relationship between gene polymorphisms and ACS severity. RESULTS: No
      significant differences were observed in the genotype and allelic frequencies of
      OPG gene 209G/A, 245T/G between the ACS and control groups. Significant
      differences were observed in the genotype and allelic frequencies of OPG gene
      1181G/C between the ACS and control groups [1181G/C GG: 92 (50.0%) vs. 43
      (63.2%), CC: 26 (14.1%) vs. 0, GC: 66 (35.9%) vs. 25 (36.8%), chi(2)=11.240,
      P=0.004; allelic gene G: 250 (67.9%) vs. 111 (81.6%), allelic gene C: 118 (32.1%)
      vs. 25 (18.4%), chi(2)=9.148, P=0.002]. No significant differences were observed
      in the genotype and allelic frequencies of OPG gene 209G/A, 245T/G and 1181G/C
      between those groups. CONCLUSIONS: There were no significant difference in
      frequencies OPG genotype and allele in polymorphisms 209G/A, 245T/C between
      patients with ACS and control group in Han population of Fujian province. There
      were difference in frequencies OPG genotype and allele in polymorphisms 1181G/C
      between patients with ACS and control group, but it was not differently
      distributed among patients with single-, double-, or triple-vessel lesion.

PMID- 23168202
TI  - [Clinical characteristics of coronary artery disease patients with reduced left
      ventricular ejection fraction and their prognostic analysis].
AB  - OBJECTIVE: To explore the relationship between reduced left ventricular ejection
      fraction (LVEF) and characteristics of coronary artery disease (CAD) and
      investigate the association between reduced LVEF and cardiovascular prognosis.
      METHODS: A total of 677 hospitalized patients with angiographic CAD were
      enrolled. All patients' clinical data were recorded. LVEF were measured, high
      sensitive C-reactive protein (hs-CRP), white blood cell (WBC) and classic
      cardiovascular risk factors were recorded after admission. All patients were
      followed up from admission. The primary end point was combination occurrence of
      major adverse cardiovascular and cerebral events (MACCE), including death,
      targeted vascular revascularization, non-fatal myocardial infarction and
      rehospitalization due to unstable angina or heart failure, transient ischemic
      attack or stroke. RESULTS: All patients were tracked for (15+/-12) months, and
      patients were divided into normal LVEF group (LVEF>=0.50, n=585) and reduced LVEF
      group (LVEF<0.50, n=92) according to LVEF level. Compared with normal LVEF group,
      reduced LVEF group had more severe coronary stenosis (Gensini score: 62.85+/
      41.45 vs. 47.68+/-33.26, P<0.05), a higher level of WBC and hs-CRP (WBC: 7.60+/
      2.71 *10(9)/L vs. 7.09+/-2.13 *10(9)/L, hs-CRP: 5.68+/-3.97 mg/L vs. 3.97+/-3.75
      mg/L, both P<0.05). A total of 146 MACCE occurred during follow-up periods.
      Compared with no-MACCE group, LVEF levels were significantly lower in MACCE group
      (0.576+/-0.113 vs. 0.603+/-0.101) and there were a higher level of hs-CRP and
      Gensini score in MACCE group (hs-CRP: 5.26+/-3.99 mg/L vs. 3.91+/-3.72 mg/L,
      Gensini score: 53.72+/-35.50 vs. 48.63+/-34.59, all P<0.05). Moreover, both of
      univariate and multivariate Cox regression analysis indicated LVEF be an
      independent predictor of MACCE in patients with CAD [univariate: relative risk
      (RR)=0.974, 95% confidence interval (95%CI) 0.960 to 0.988, P=0.000;
      multivariate: RR=0.979, 95%CI 0.961 to 0.998, P=0.033]. Kaplan-Meier analysis
      suggested that patients with reduced LVEF had an increased MACCE occurrence
      (chi(2)=14.56, P<0.05). CONCLUSION: LVEF level may be associated with coronary
      artery severity, and could be independently predict the prognosis of CAD.

PMID- 23168203
TI  - [Feasibility of focused transthoracic echocardiography in intensive care unit
      performed by intensivists].
AB  - OBJECTIVE: To assess the clinical applicability of focused transthoracic
      echocardiography (TTE) in intensive care unit (ICU) performed by intensivists and
      its impacts on clinical managements. METHODS: After 12-hour tutorials and initial
      cardiac clinical assessments, intensivists performed a focused TTE (2-4 views of
      2D, without Doppler or M mode) examination in 88 patients to assess left
      ventricular function and left ventricular volume status, and rule out local
      ventricular wall motion abnormalities and significant pericardial effusions. Each
      investigation was immediately reviewed by an echocardiograph to determine the
      technical quality of the TTE and the accuracy of the intensivist's
      interpretation. RESULTS: Intensivists successfully performed a diagnostic focused
      TTE in 86 patients (97.7%) and interpreted correctly in 75 patients (85.2%).
      Management including fluid treatment, inotropic agent and vasoactive agent in
      22.7% of patients were changed directly based on the focused TTE, 45.5% of
      patients were provided with valuable information, while 31.8% of them with non
      valuable information. The mean focused TTE acquisition time of the intensivist
      was (11.2+/-5.2) minutes. CONCLUSIONS: After a brief standard training in using
      echocardiographic system, intensivists can successfully performed and correctly
      interpreted a focused TTE for critically ill patients. Our study demonstrates
      that new information can be provided by focused TTE, which can alter management
      in a significant number of patients. The present study supports incorporating
      bedside goal-directed, focused TTE into intensivists' training programs in China.

PMID- 23168204
TI  - [Analysis of death characteristics and its potential mechanisms in rats with
      endotoxin- induced cardiomyopathy].
AB  - OBJECTIVE: To approach the changes in heart failure and dying regularity of rats
      with endotoxin-induced cardiomyopathy, and to offer some help for clinical
      diagnosing and further investigation. METHODS: Injecting refined endotoxin (10
      mg/kg) via vein of Wistar rats. The first experiment: antidromic observing the
      endotoxic rats from death to the beginning to discover the performance of clinic
      heart function which could forecast death. The second experiment: setting 6 rats
      per group, respectively killing the rats at 4, 8, 16, 24, 32, 40, 48 and 72 hours
      after endotoxin injection, and killing 6 normal rats as control group, getting
      the tissue of left ventricle for biochemistry test, routine pathological
      examination, transmission electron microscope examination, expression level of
      alpha(1)-actin gene with reverse transcription-polymerase chain reaction (RT
      PCR), and serum creatine  kinase  (CK)  was  test  within 24 hours. RESULTS: The
      first experiment: heart rate (HR) and left ventricular end-systolic pressure
      (LVESP) of endotoxic rats began significant lower than normal at 4 hours before
      death (F(1)=22.032, P(1)=0.000; F(2)=29.420, P(2)=0.000), maximum rate of
      rise/drop of left ventricular pressure (+/-dp/dt max)  began  significant  lower 
      than  normal  at 8 hours before death (F(1)=17.272, P(1)=0.000; F(2)=19.685,
      P(2)=0.000), left ventricular end-diastolic pressure (LVEDP) showed no
      significant during the whole time (F=0.265, P=0.988). The heart function of all
      the rats showed no significant changes in the first 4 hours after injection.
      Mortality was 73.9% from injection to 24 hours later. Most of them died in 8-16
      hours after injection. The one who had survived over 24 hours could have 2/3
      probability to survive to 48 hours. The second experiment: CK in serum of
      different groups showed no significant difference (F=0.402, P=0.805), but showed
      obvious discreteness in each group except normal group. Electron microscopy and
      pathological examination showed obvious intracellular and intercellular damage
      since 8 hours later from injection. Pathology displayed that cells range
      disorder, mitochondria swelling, capillary hemorrhage, transverse striation
      disappearing, construction of myocardial cell loosing, and lateral dissociation
      phenomena. Electron microscopy discovered that the fiber direction and transverse
      striation became vague and disappeared, mitochondria got injury, the fiber became
      disordered, cell-cell junction were damaged seriously. Compared with the control
      group (0.637+/-0.160), the gene expression level of alpha(1)-actin decreased
      after endotoxin injection. The value dropped to the bottom at 8 hours (0.493+/
      0.067) after injection and then rised slowly but dropped to the second wave
      trough again at 32 hours (0.875+/-0.128), but had no statistic significance; the
      expression of alpha(1)-actin gene eventually rised significantly at 40, 48, 72
      hours after injection (2.231+/-0.545, 1.850+/-0.436, 2.062+/-0.340, all P<0.01).
      CONCLUSIONS: Endotoxic myocardiopathy does not result from plasmalemma destroy.
      Damage of alpha(1)-actin is a significantly important factor for endotoxic
      myocardiopathy.

PMID- 23168205
TI  - [Protective effect of melatonin on myocardial injury in severely- burned rats].
AB  - OBJECTIVE: To investigate the protective effect of melatonin (MLT) on myocardial
      injury in severely-burned rats and its mechanism. METHODS: A total of 30 Sprague
      Dawley (SD) rats were randomly assigned to three groups: sham group, burn group
      and MLT group, each n=10. The dorsal skin of animal was immersed into boiling
      water for 15 seconds to induce 30% total body surface area (TBSA) full-thickness
      burn, or immersed into 37 centigrade water for sham operation. Immediately after
      burn, the animals in burn group and MLT group were given intraperitoneally
      vehicle (1% alcohol in normal saline) or MLT (10 mg/kg) respectively. Six hours
      postburn, the blood from tail vessel was collected for serum preparation. After
      sacrificed, the myocardial tissues of rats were collected for the determination
      of malondialdehyde (MDA) and reduced glutathione (GSH) as well as glutathione
      peroxidase (GSH-Px) and myeloperoxidase (MPO) activities. Serum levels of
      creatine kinase (CK) and lactate dehydrogenase (LDH) were also estimated.
      RESULTS: Compared with the sham control, burn injury increased MDA by 66.7%
      (1.55+/-0.17 nmol/mg vs. 0.93+/-0.05 nmol/mg) and decreased GSH by 27.8% (13.58+/
      0.33 nmol/mg vs. 18.82+/-0.55 nmol/mg, both P<0.01) in myocardial tissues, GSH-Px
      activity was also slightly inhibited (74.04+/-3.42 nmol*min(-1)*mg(-1) vs.
      93.79+/-3.76 nmol*min(-1)*mg(-1), P<0.05), but MPO level was found to increase to
      2.8 folds (9.43+/-1.15 U/g vs. 3.41+/-0.27 U/g, P<0.01). These changes indicated
      the occurrence of oxidative stress in myocardial tissues after severe burn. MLT
      treatment relieved most of the abnormality with significant statistical
      significances (MDA: 0.89+/-0.08 nmol/mg vs. 1.55+/-0.17 nmol/mg, GSH: 17.23+/
      0.54 nmol/mg vs. 13.58+/-0.33 nmol/mg, MPO: 6.91+/-0.51 U/g vs. 9.43+/-1.15 U/g,
      P<0.05 or P<0.01). In addition, the serum levels of CK and LDH in burn group
      increased to 37.8 folds and 7.4 folds respectively (both P<0.01). MLT treatment
      reduced CK by 32.9% and reduced LDH by 21.2% (P<0.05 and P<0.01). CONCLUSION: MLT
      treatment exerts the protective effect on myocardial injury in severely-burned
      rats, which is attributed predominantly to its inhibition on burn-induced
      oxidative stress injury.

PMID- 23168206
TI  - [The protective effect of propofol pretreatment on glutamate injury of neonatal
      rat brain slices].
AB  - OBJECTIVE: To study the protective effect of propofol precondition against
      glutamate (Glu) neurotoxicity to neonatal rat cerebrocortical slices. METHODS:
      Brain slices of Sprague-Dawley (SD) rats were cultured in vitro and observed the
      morphologic changes. Brain slices were randomly divided into three groups: blank
      control group, Glu injury group (1 mmol/L Glu for 0.5 hour), propofol
      precondition group (20 mg/L propofol for 24 hours), each n=12. Changes in
      pathological and ultra-structure of cells were observed using microscope. Lactate
      dehydrogenase (LDH) leakage rate was measured. Meanwhile, the expression of glial
      fibrillary acidic protein (GFAP) was detected by immunohistochemical technology,
      then the positive cell were counted. RESULTS: Cultured brain slices of cell were
      intact and survived well. Hematoxylin-eosin (HE) staining, electron microscopy
      and LDH test results showed that cerebral film neuron severely damage, gliosis,
      edema, LDH leakage rate in Glu injury group were significantly more severe
      compared with blank control group [(68.5+/-2.0)% vs. (16.0+/-2.5)%, P<0.01].
      Reduce the brain slice of the propofol pretreatment group of neuronal cell jury,
      cell shape recovery significantly reduced LDH leakage rate compared with the Glu
      injury group [(38.5+/-2.4)% vs. (68.5+/-2.0)%, P<0.05]. Immunohistochemical
      detection of GFAP expression of Glu injury group glial cell body swelling,
      producing increase in the number of GFAP positive reaction strong, the number of
      positive cells compared with blank control group was significantly increased
      (50+/-5 cells/HP vs. 10+/-3 cells/HP, P<0.01). The recovery of propofol
      pretreatment group glial cell morphology, cell processes slender GFAP positive
      reaction decreased the number of positive cells compared with the Glu injury
      group was significantly decreased (30+/-4 cells/HP vs. 50+/-5 cells/HP, P<0.05).
      CONCLUSION: Propofol pretreatment has protective effect against Glu injured rat
      cerebrocortical slices.

PMID- 23168207
TI  - [Observation and multifactor analysis of refractory medium-severe heart failure
      by micro-inflammation modification in uremic patients].
AB  - OBJECTIVE: To investigate the therapeutic strategies and prognostic factors of
      refractory medium-severe heart failure in uremic patients. METHODS: A single
      center, self control clinical research was conducted, and the data consisted of
      30 uremic patients with refractory medium-severe heart failure undergoing
      maintenance hemodialysis (MHD), who received routine combined modality therapy
      and Xuebijing injection (to modify micro-inflammation). The systolic function of
      the left ventricle was compared before and after therapy. Multiple linear
      regression models were established to predict the improvements of systolic
      function of ventricle. Relationship between the accumulated dose of Xuebijing
      injection and changes of C-reactive protein (DeltaCRP) was observed. RESULTS: The
      values of left ventricle ejection fraction (LVEF), fractional shortening (FS),
      and stroke volume (SV) after therapy were improved compared with those before
      therapy [LVEF: 0.42+/-0.07 vs. 0.34+/-0.04, FS: (21.07+/-3.83)% vs. (16.33+/
      2.43)%, SV: 66.83+/-7.00 ml vs. 52.20+/-7.62 ml, all P<0.01]. In terms of cardiac
      output (CO), there was no statistical difference before and after therapy (4.77+/
      0.65 L/min vs. 4.49+/-0.68 L/min, P>0.05). In the multiple linear regression
      models of DeltaLVEF, DeltaFS and DeltaSV, the independent variables that affect
      dependent variables included age, DeltaCRP, changes of hemoglobin (DeltaHb),
      accumulated dose of Xuebijing injection, changes of HCO(3)(-) (Delta HCO(3)(-)),
      changes of serum creatinine (DeltaSCr), Hb and CRP after therapy, the factors and
      weights of which had slight variation on accordance with different dependent
      variables. There was significant positive correlation between accumulated dose of
      Xuebijing injection and DeltaCRP (r=0.561, P=0.001). CONCLUSIONS: Xuebijing
      injection can improve heart function in uremic patients by modifying micro
      inflammation, whose accumulated dose and therapeutic effect show positive
      correlation. In addition the improvement of heart failure has something to do
      with age, DeltaHb, Hb after therapy, the correction of acidosis and dialysis
      sufficiency.

PMID- 23168208
TI  - [Early treatment of atelectasis by bronchoscopy in craniotomy patients].
AB  - OBJECTIVE: To investigate the safety and effects of early bronchoscopy on
      atelectasis of the ventilation patients, whom had experienced craniotomy for
      severe cranial trauma and hemorrhage. METHODS: Fifty-five patients suffered from
      severe cranial trauma and hemorrhage with Glascow coma scores (GCS) less than 8
      complicated by atelectasis after craniotomy were early given sputum suction by
      bronchoscope via extratracheal intubation and broncho-alveolar lavage (BAL)
      during tracheal intubation and mechanical ventilation. During the treatment,
      patients' consciousness, vital signs and arterial blood gas were closely
      monitored. The relevant data, before, during (5, 10, and 25 minutes),
      bronchoscopy treatment completed and 30 minutes after bronchoscopy, were recorded
      and analyzed. RESULTS: Eighty-two time of bronchoscopies and 111 time of local
      BALs in 55 patients were completed and were effective for atelectasis. The
      patient's GCS (5.6+/-2.5 vs. 5.4+/-2.6, P>0.05), heart rate (HR), respiratory
      rate (RR), systolic blood pressure (SBP), blood oxygenous saturation (SaO(2))
      were not deteriorated during bronchoscopy. Compared with pre-bronchoscopy, the HR
      and SBP   decreased   (HR:  88.2+/-14.2 bpm vs.  98.2+/-18.3 bpm,  SBP: 110.6+/
      18.2 mm Hg vs. 118.4+/-18.5 mm Hg, both P<0.05), and SaO(2) increased (0.982+/
      0.022 vs. 0.945+/-0.035, P<0.05), pH, arterial partial pressure of oxygen
      (PaO(2)) and arterial partial pressure of carbon dioxide (PaCO(2)) had no
      significant changes during bronchoscopy. There was obviously increased in PaO(2)
      (84.5+/-14.4 mm Hg, 81.6+/-18.2 mm Hg vs. 76.2+/-15.4 mm Hg, both P<0.05), and
      decreased in PaCO(2) (27.0+/-12.8 mm Hg, 29.3+/-18.2 mm Hg vs. 36.5+/-11.6 mm Hg,
      both P<0.05) respectively, significantly decreased in alveolar arterial pressure
      of oxygen difference [P ((A-a))O(2)] at 10 minutes and 25 minutes, and at the
      time bronchoscopy treatment completed and the time 30 minutes after compared with
      before bronchoscopy (36.1+/-4.7 mm Hg, 32.4+/-6.2 mm Hg, 32.5+/-5.2 mm Hg, 31.2+/
      7.2 mm Hg vs. 38.5+/-5.6 mm Hg, all P<0.05). All patients had not encounter side
      effects related with bronchoscopy and ventilation. CONCLUSION: The bronchoscope
      via extratracheal intubation for sputum suction and BAL were safe and effective
      treatment to the patients suffered from severe cranial trauma or hemorrhage
      complicated by atelectasis after craniotomy during mechanical ventilation,
      without obvious changes of the vital signs.

PMID- 23168209
TI  - [Effects of ulinastatin on Toll like receptor 4 expression in endotoxin induced
      myocardial injury rats].

PMID- 23168210
TI  - Laughing, grooming, and pub science.
AB  - On the basis of naturalistic observations of people conversing and laughing in
      pubs, a new study suggests that the 'grooming-at-a-distance' of laughter provides
      a three-fold increase in grooming group size, potentially explaining how hominins
      evolved social groups that are considerably larger than those of other primates.

PMID- 23168211
TI  - Population genetics of Parascaris equorum based on DNA fingerprinting.
AB  - The large roundworm of horses, Parascaris equorum is considered ubiquitous in
      breeding operations, and is regarded as a most important helminth pathogen of
      foals. Over the past decade, this parasite has been reported increasingly
      resistant to anthelmintic drugs worldwide. This paper reports analysis of the
      population genetic structure of P. equorum. Adult parasites (n=194) collected
      from Sweden, Norway, Iceland, Germany, Brazil and the USA were investigated by
      amplified restriction fragment length polymorphism (AFLP) analysis. The genetic
      variation was low (Hj=0.12-0.4), for the global population of worms. This was
      accompanied by a weak degree of population structure (Fst=0.2), low gene flow
      (Nm=1.0) and low mutation rate (4 NMU=0.07). Thus, the low genetic diversity is
      probably a result of a low mutation rate in DNA, although the gene flow (due to
      global movement of horses) is large enough to allow the spread of novel
      mutations. Surprisingly, isolates from Icelandic horses were not found to be
      different from other isolates, in spite of the fact that these have been isolated
      for thousands of years. The study indicates that the global P. equorum population
      is essentially homogenous, and continents do not appear to be strong barriers for
      the population structure of this species. Consequently, the potential spread of
      rare anthelmintic resistance genes may be rapid in a homogenous population.

PMID- 23168212
TI  - A case report of chronic myelogenous leukemia in a patient with multiple myeloma
      and a review of the literature.

PMID- 23168214
TI  - Transposition of a lingual thyroid to the submandibular space using a modified
      technique.
AB  - OBJECTIVE: We report a modified surgical technique for transplanting an ectopic,
      lingual thyroid to the submandibular space, in order to maintain thyroid function
      while relieving obstructive symptoms. CASE REPORT: A 52-year-old woman complained
      of progressive dysphagia and dyspnoea. Ectopic lingual thyroid tissue was
      diagnosed. The ectopic thyroid gland was transplanted into the submandibular
      region via a lateral pharyngeal approach. A random muscle pedicle was prepared to
      provide a vascular supply to the transposed gland. RESULTS: Twelve-month follow
      up confirmed the survival of the transplanted thyroid gland, with preserved
      thyroid function. CONCLUSION: Surgical transplantation of a lingual thyroid to
      the submandibular region offers an alternative treatment method for this anomaly,
      which avoids the need for resection and lifelong thyroxine replacement.

PMID- 23168213
TI  - A pilot survey on the quality of life in respiratory rehabilitation carried out
      in COPD patients with severe respiratory failure: preliminary data of a novel
      Inpatient Respiratory Rehabilitation Questionnaire (IRRQ).
AB  - BACKGROUND: Measuring the state of health is a method for quantifying the impact
      of an illness on the day-to-day life, health and wellbeing of a patient,
      providing a quantitative measure of an individual's quality of life (QoL). QoL
      expresses patient point of view by a subjective dimension and can express the
      results of medical intervention. Pulmonary rehabilitation is an essential
      component in the management of COPD patients, and measuring QoL has become a
      central focus in the study of this disease.Although nowadays several
      questionnaires for measuring the QoL in COPD patients are available, there are no
      questionnaires specifically developed for evaluating QoL in COPD patients
      undergoing respiratory rehabilitation.The aim of this study was to develop a
      novel questionnaire for the QoL quantification in COPD patients undergoing in
      patient pulmonary rehabilitation program. METHODS: The questionnaire,
      administered to COPD patients undergoing long-term oxygen therapy into a
      respiratory rehabilitation ward, was developed by a simple and graphic layout to
      be administered to elderly patients. It included one form for admission and
      another for discharge. It included only tips related to the subjective components
      of QoL that would be relevant for patient, although likely not strictly related
      to the respiratory function.A descriptive analysis was performed for the socio
      demographic characteristics and both the non-parametric Wilcoxon T-test and the
      Cronbach's alpha index were calculated for evaluating the sensitivity of the
      questionnaire to the effects of respiratory rehabilitation and for identifying
      its consistency. RESULTS: The physical and psychological condition of the 34 COPD
      patients improved after the rehabilitative treatment and this finding was
      detected by the questionnaire (overall improvement: 14.2+/-2.5%), as confirmed by
      the non-parametric Wilcoxon test (p<0.01). The consistency detected by the
      Cronbach's alpha was good for both the questionnaire at admission and at
      discharge (0.789+/-0.084 and 0.784+/-0.145, respectively), although some items
      did not adequately measure the intended outcome. CONCLUSIONS: This proposed
      questionnaire represents a substantial innovation compared to previous methods
      for evaluating the QoL, since it has been specifically designed for hospitalized
      COPD patients undergoing respiratory rehabilitation with serious respiratory
      deficiency, allowing to effectively determining the QoL in these patients.

PMID- 23168215
TI  - A comparative study of the metabolic response in rainbow trout and Nile tilapia
      to changes in dietary macronutrient composition.
AB  - Metabolic mechanisms underlying the divergent response of rainbow trout
      (Oncorhynchus mykiss) and Nile tilapia (Oreochromis niloticus) to changes in
      dietary macronutrient composition were assessed. Fish were fed one of four
      isoenergetic diets having a digestible protein-to-digestible energy (DP:DE) ratio
      above or below the optimal DP:DE ratio for both species. At each DP:DE ratio, fat
      was substituted by an isoenergetic amount of digestible starch as the non-protein
      energy source (NPE). Dietary DP:DE ratio did not affect growth and only slightly
      lowered protein gains in tilapia. In rainbow trout fed diets with low DP:DE
      ratios, particularly with starch as the major NPE source, growth and protein
      utilisation were highly reduced, underlining the importance of NPE source in this
      species. We also observed species-specific responses of enzymes involved in amino
      acid catabolism, lipogenesis and gluconeogenesis to dietary factors. Amino acid
      transdeamination enzyme activities were reduced by a low dietary DP:DE ratio in
      both species and in tilapia also by the substitution of fat by starch as the NPE
      source. Such decreased amino acid catabolism at high starch intakes, however, did
      not lead to improved protein retention. Our data further suggest that a
      combination of increased lipogenic and decreased gluconeogenic enzyme activities
      accounts for the better use of carbohydrates and to the improved glycaemia
      control in tilapia compared with rainbow tront fed starch-enriched diets with low
      DP:DE ratio.

PMID- 23168216
TI  - The changing pattern of bacterial meningitis in adult patients at a large
      tertiary university hospital in Barcelona, Spain (1982-2010).
AB  - BACKGROUND: We conducted a prospective, observational study in Barcelona (Spain)
      to determine changes in the spectrum of adult patients with bacterial meningitis
      (BM) over a 29-year period. METHODS: The observation was divided into two
      periods: 1982-1995 (I) and 1996-2010 (II). All patients underwent clinical
      examination on admission and at discharge following a predefined protocol.
      RESULTS: We evaluated 635 episodes of BM. The most frequent etiologic agents were
      Neisseria meningitidis and Streptococcus pneumoniae in periods I and II,
      respectively. Patients in period II were older (Median: 47.5 [95%CI: 23.0-64.5]
      vs. 58.0 [39.0-73.0] years, P<0.0001), had a longer interval from admission to
      therapy (Median: 2.3 [95%CI: 1.0-5.0] vs. 4.0 [2.0-12.0] hours, P<0.0001), and
      more frequently had co-morbid conditions (39.1% vs. 62%, P<0.0001). Meningococcal
      meningitis decreased by 66% (P<0.0001), whereas meningitis by Listeria
      monocytogenes increased by 110% (P=0.0007) in period II. There were no
      differences in the overall case-fatality and post-meningitic sequelae rates
      between both periods. CONCLUSIONS: BM in adult patients has substantially changed
      over 29 years in terms of population affected, aetiology, and management, but not
      in terms of its overall mortality rate and appearance of post-meningitic
      sequelae.

PMID- 23168217
TI  - Prevalence of Fabry disease in young patients with cryptogenic ischemic stroke.
AB  - BACKGROUND: A German study diagnosed 4% of young cryptogenic ischemic stroke
      patients with Fabry disease, an X-linked lysosomal storage disease caused by
      mutations in the alpha-galactosidase A (alpha-GAL-A) gene resulting in an
      accumulation of glycosphingolipids. A lower prevalence was found in other
      geographic regions. AIM: To determine the prevalence of Fabry disease in a
      Canadian population of young cryptogenic ischemic stroke patients. MATERIALS AND
      METHODS: Patients with cryptogenic ischemic stroke at age 16-55 were
      retrospectively identified in our institutional stroke database and underwent a
      focused clinical evaluation. We sequenced the alpha-GAL-A gene and measured the
      levels of blood globotriaosylsphingosine in subjects with mutations of
      undetermined pathogenicity. Fabry disease was diagnosed in patients with
      pathogenic mutations or increased levels of blood globotriaosylsphingosine.
      RESULTS: Ninety-three of 100 study subjects had normal alpha-GAL-A gene
      polymorphisms. Seven had mutations of undetermined pathogenicity, including one
      with increased globotriaosylsphingosine (prevalence, 1%; 95% confidence interval,
      <.01%-6%). No subjects had angiokeratomas or other clinical manifestations of
      Fabry disease. Investigation results suggestive of Fabry disease (idiopathic
      hypertrophic cardiomyopathy, proteinuria, vertebrobasilar dolichoectasia, and the
      pulvinar sign) were found only in subjects with normal alpha-GAL-A genes. Apart
      from the 100 study subjects, our database included another patient with a family
      history of Fabry disease and a pathogenic mutation identified before her ischemic
      stroke presentation as the first clinical manifestation of Fabry disease. Both
      Fabry patients experienced recurrent ischemic stroke. CONCLUSIONS: Fabry disease
      accounts for a small proportion of young Canadians with cryptogenic ischemic
      stroke. Identification of Fabry biomarkers remains a research priority to
      delineate stroke patients disserving routine screening.

PMID- 23168218
TI  - Cranial neurosurgery procedure utilization among patients with acute ischemic
      stroke.
AB  - BACKGROUND: Concerns about ready access to neurosurgery after acute ischemic
      stroke (AIS) may delay or prevent intravenous thrombolysis, thereby leading to
      poor outcomes. A randomized trial exploring the need for back-up neurosurgery in
      AIS is unlikely. However, insight may be gained from routine clinical practice.
      We analyzed the odds and temporal trends of cranial neurosurgery procedure use in
      patients with AIS using a large U.S. administrative database. METHODS: Data from
      AIS patients in the Nationwide Inpatient Sample (October 1998 to 2006) who
      underwent a cranial neurosurgical procedure were analyzed. Multivariate logistic
      regression with covariate adjustment was used for statistical analysis. Results
      were stratified by thrombolysis status. Intracerebral hemorrhage (ICH) was used
      as a key covariate. RESULTS: Intravenous thrombolysis use increased significantly
      over time (0.8% to 2.5%; P<.001). Cranial neurosurgical procedures were observed
      infrequently but increased significantly over time (0.12% to 0.19%; P=.0013), and
      thrombolysis doubled the odds of a procedure (odds ratio 2.18; 95% confidence
      interval 1.48-3.21; P<.001). However, thrombolysis only significantly increased
      the odds of a neurosurgical procedure in the absence of ICH (P<.001).
      CONCLUSIONS: Thrombolysis should probably not be withheld from eligible AIS
      patients, even if a concern exists about the lack of readily available
      neurosurgery, because neurosurgical procedure use is low in routine clinical
      practice, even after intravenous thrombolysis. Future studies and prospective
      data might help define the need for standby neurosurgery after AIS and provide
      further focus on the specific linkage to ICH as a possible mediator variable.

PMID- 23168219
TI  - Adipose-specific deletion of TFAM increases mitochondrial oxidation and protects
      mice against obesity and insulin resistance.
AB  - Obesity and type 2 diabetes are associated with mitochondrial dysfunction in
      adipose tissue, but the role for adipose tissue mitochondria in the development
      of these disorders is currently unknown. To understand the impact of adipose
      tissue mitochondria on whole-body metabolism, we have generated a mouse model
      with disruption of the mitochondrial transcription factor A (TFAM) specifically
      in fat. F-TFKO adipose tissue exhibit decreased mtDNA copy number, altered levels
      of proteins of the electron transport chain, and perturbed mitochondrial function
      with decreased complex I activity and greater oxygen consumption and uncoupling.
      As a result, F-TFKO mice exhibit higher energy expenditure and are protected from
      age- and diet-induced obesity, insulin resistance, and hepatosteatosis, despite a
      greater food intake. Thus, TFAM deletion in the adipose tissue increases
      mitochondrial oxidation that has positive metabolic effects, suggesting that
      regulation of adipose tissue mitochondria may be a potential therapeutic target
      for the treatment of obesity.

PMID- 23168221
TI  - How to make a difference: mechanisms of protein and nucleic acid modifying
      enzymes.

PMID- 23168223
TI  - Construction of silica-enhanced S-layer protein cages.
AB  - The work presented here shows for the first time that it is possible to silicify
      S-layer coated liposomes and to obtain stable functionalized hollow nano
      containers. For this purpose, the S-layer protein of Geobacillus
      stearothermophilus PV72/p2 was recombinantly expressed and used for coating
      positively charged liposomes composed of dipalmitoylphosphatidylcholine,
      cholesterol and hexadecylamine in a molar ratio of 10:5:4. Subsequently, plain
      (uncoated) liposomes and S-layer coated liposomes were silicified. Determination
      of the charge of the constructs during silicification allowed the deposition
      process to be followed. After the particles had been silicified, lipids were
      dissolved by treatment with Triton X-100 with the release of previously entrapped
      fluorescent dyes being determined by fluorimetry. Both, zeta-potential and
      release experiments showed differences between silicified plain liposomes and
      silicified S-layer coated liposomes. The results of the individual preparation
      steps were examined by embedding the respective assemblies in resin, ultrathin
      sectioning and inspection by bright-field transmission electron microscopy (TEM).
      Energy filtered TEM confirmed the successful construction of S-layer based silica
      cages. It is anticipated that this approach will provide a key to enabling
      technology for the fabrication of nanoporous protein cages for applications
      ranging from nano medicine to materials science.

PMID- 23168222
TI  - Effect of biodegradation and de novo matrix synthesis on the mechanical
      properties of valvular interstitial cell-seeded polyglycerol sebacate
      polycaprolactone scaffolds.
AB  - The development of living heart valves that grow with the patient is a promising
      strategy for heart valve replacements in pediatric patients. Despite active
      research in the field of tissue engineered heart valves there have been limited
      efforts to optimize the balance between biodegradation of the scaffolds and de
      novo extracellular matrix (ECM) synthesis by cells and study their consequences
      on the mechanical properties of the cell-seeded construct. This study
      investigates the effect of in vitro degradation and ECM secretion on the
      mechanical properties of hybrid polyester scaffolds. The scaffolds were
      synthesized from blends of fast degrading polyglycerol sebacate (PGS) and slowly
      degrading polycaprolactone (PCL). PGS-PCL scaffolds were electrospun using a 2:1
      ratio of PGS to PCL. Accelerated hydrolytic degradation in 0.1 mM sodium
      hydroxide revealed 2-fold faster degradation of PGS-PCL scaffolds compared with
      PCL scaffolds. Thermal analysis and scanning electron microscopy demonstrated
      marginal change in PCL scaffold properties, while PGS-PCL scaffolds showed
      preferential mass loss of PGS and thinning of the individual fibers during
      degradation. Consequently, the mechanical properties of PGS-PCL scaffolds
      decreased gradually with no significant change for PCL scaffolds during
      accelerated degradation. Valvular interstitial cells (VICs) seeded on PGS-PCL
      scaffolds showed higher ECM protein secretion compared with PCL. Thus the
      mechanical properties of the cell-seeded PCL scaffolds did not change
      significantly compared with acellular scaffolds, probably due to slower
      degradation and ECM deposition by VICs. In contrast, the PGS-PCL scaffolds
      exhibited a gradual decrease in the mechanical properties of the acellular
      scaffolds due to degradation, which was compensated for by new matrix secreted by
      VICs seeded on the scaffolds. Our study demonstrated that the faster degrading
      PGS component of PGS-PCL accelerated the degradation rate of the scaffolds. VICs,
      on the other hand, were able to remodel the synthetic scaffold, depositing new
      matrix proteins and maintaining the mechanical properties of the scaffolds.

PMID- 23168220
TI  - Energy intake and exercise as determinants of brain health and vulnerability to
      injury and disease.
AB  - Evolution favored individuals with superior cognitive and physical abilities
      under conditions of limited food sources, and brain function can therefore be
      optimized by intermittent dietary energy restriction (ER) and exercise. Such
      energetic challenges engage adaptive cellular stress-response signaling pathways
      in neurons involving neurotrophic factors, protein chaperones, DNA-repair
      proteins, autophagy, and mitochondrial biogenesis. By suppressing adaptive
      cellular stress responses, overeating and a sedentary lifestyle may increase the
      risk of Alzheimer's and Parkinson's diseases, stroke, and depression. Intense
      concerted efforts of governments, families, schools, and physicians will be
      required to successfully implement brain-healthy lifestyles that incorporate ER
      and exercise.

PMID- 23168224
TI  - Artificial extracellular matrices composed of collagen I and high-sulfated
      hyaluronan promote phenotypic and functional modulation of human pro-inflammatory
      M1 macrophages.
AB  - The sequential phases of biomaterial integration and wound healing require
      different macrophage functions mediated by distinct macrophage subsets. During
      the initial phase of healing, pro-inflammatory M1 macrophages (MPhi1) are
      required to clear the wound from microbes and debris; however, their unopposed,
      persistent activation often leads to disturbed integration of biomaterials and
      perturbed wound healing. Here we investigated whether pro-inflammatory macrophage
      functions are affected by immunomodulatory biomaterials based on artificial
      extracellular matrices (aECM). To address this issue, we tested the capacity of
      two-dimensional aECM consisting of collagen I and hyaluronan or sulfated
      derivatives of hyaluronan to affect functions of in vitro polarized human pro
      inflammatory MPhi1. The aECM containing high-sulfated hyaluronan substantially
      decreased inflammatory macrophage functions, including pathogen uptake and
      release of the pro-inflammatory cytokines tumor necrosis factor alpha and
      interleukin-12 due to impaired activation of nuclear factor "kappa-light-chain
      enhancer" of activated B-cells. Moreover, these macrophages secreted
      immunregulatory IL-10 and showed reduced activity of the transcription factors
      signal transducer and activator of transcription 1 and interferon-regulating
      factor 5, both controlling macrophage polarization to MPhi1 subsets. Our data
      reveal that the collagen I matrix containing high-sulfated hyaluronan possesses
      immunomodulating properties and dampens inflammatory macrophage activities by
      impeding signaling pathways crucial for polarization of pro-inflammatory MPhi1.
      We therefore suggest this aECM as a promising coating for biomaterials to
      modulate inflammatory macrophage functions during the healing response and
      recommend its further testing as a three-dimensional construct and in in vivo
      models.

PMID- 23168226
TI  - Comparative study of management of inferior turbinate hypertrophy using
      turbinoplasty assisted by microdebrider or 980 nm diode laser.
AB  - OBJECTIVE: This study aimed to compare the outcomes of turbinoplasty assisted by
      microdebrider and by diode laser (980 nm wavelength). METHODS: Forty patients
      suffering from bilateral nasal obstruction were randomly divided into two equal
      groups. One group was managed with microdebrider-assisted turbinoplasty and the
      other with diode laser assisted turbinoplasty. The patients were followed up for
      six months post-operatively. RESULTS: After six months, total success rates were
      90 per cent for the microdebrider group and 85 per cent for the diode laser
      group. There were no significant differences between the two groups regarding
      success rate, post-operative complications or operative time. CONCLUSION: These
      two techniques are equally safe, reliable, successful and non-invasive.

PMID- 23168225
TI  - Evaluation of bone regeneration in implants composed of hollow HA microspheres
      loaded with transforming growth factor beta1 in a rat calvarial defect model.
AB  - Implants that serve simultaneously as an osteoconductive matrix and as a device
      for local growth factor delivery may be required for optimal bone regeneration in
      some applications. In the present study, hollow hydroxyapatite (HA) microspheres
      (106-150MUm) in the form of three-dimensional (3-D) scaffolds or individual
      (loose) microspheres were created using a glass conversion process. The capacity
      of the implants, with or without transforming growth factor beta1 (TGF-beta1), to
      regenerate bone in a rat calvarial defect model was compared. The 3-D scaffolds
      supported the proliferation and alkaline phosphatase activity of osteogenic MLO
      A5 cells in vitro, showing their cytocompatibility. Release of TGF-beta1 from the
      3-D scaffolds into phosphate-buffered saline ceased after 2-3 days when ~30% of
      the growth factor was released. Bone regeneration in the 3-D scaffolds and the
      individual microspheres increased with time from 6 to 12 weeks, but it was
      significantly higher (23%) in the individual microspheres than in the 3-D
      scaffolds (15%) after 12 weeks. Loading with TGF-beta1 (5MUg per defect) enhanced
      bone regeneration in the 3-D scaffolds and individual microspheres after 6 weeks,
      but had little effect after 12 weeks. 3-D scaffolds and individual microspheres
      with larger HA diameter (150-250MUm) showed better ability to regenerate bone.
      Based on these results, implants composed of hollow HA microspheres show
      promising potential as an osteoconductive matrix for local growth factor delivery
      in bone regeneration.

PMID- 23168227
TI  - Pellagra revealing a congenital duodenal diaphragm in an adult.
AB  - Pellagra is a nutritional disease caused by the deficiency of niacin. It is a
      clinical syndrome characterized by four "D's": diarrhea, dermatitis, dementia and
      ultimately death. We describe a case of pellagra as the initial presentation of
      congenital duodenal diaphragm. 

PMID- 23168228
TI  - Sequential therapy versus standard triple-drug therapy for Helicobacter pylori
      eradication: result of the HPFEZ randomised study.
AB  - OBJECTIVE: The aim of this study was to assess and compare the efficacy and
      safety of sequential treatment with standard triple therapies in a located
      population in Morocco. METHODS: Consecutive H. pylori-positive patients with
      endoscopy-proven ulcer or non ulcer dyspepsia were prospectively randomized in
      the trial into one of three groups: AM and AC group were administered a tri
      therapy for 7 days including PPI + amoxicillin + metronidazole (AM
      group)/clarithromycin (AC group) and SQ group was administered a sequential
      regimen consisting of PPI + amoxicillin for 5 days followed by PPI +
      clarithromycin + metronidazole for the remaining 5 days. Eradication was
      confirmed by 13C-urea breath test 3 months after the end of the treatment.
      RESULTS: Groups AM, AC and SQ included respectively 104, 115 and 104 patients.
      They were comparable in terms of age, sex, clinical and endoscopic presentation.
      The rate of H. pylori eradication with sequential therapy was found at 94.2%
      (n=98) in ITT and 96% (n=98) in PP. It was higher than those found in the AM
      group: 70% (n=73) in ITT and 70.8% (n=73) in PP and the AC group: 78.2% (n=90) in
      ITT and 79.6% (n=90) in PP (0.001). The prevalence of side effects following the
      sequential treatment was 9.6% (n=10) versus 22% (n=22) and 27.8% (n=32) in the AM
      and AC groups, respectively, (P=0.006). CONCLUSIONS: Sequential treatment was
      better tolerated and achieved a significantly higher eradication rate of H.
      pylori compared with standard triple therapies in this population.

PMID- 23168229
TI  - Superior mesenteric artery thrombosis related to double balloon enteroscopy in a
      patient with Crohn's disease.

PMID- 23168230
TI  - Hypotensive and heart rate-lowering effects in rats receiving milk fermented by
      specific Lactococcus lactis strains.
AB  - Previous studies have demonstrated that milk fermented by specific Lactococcus
      lactis strains significantly inhibits the activity of angiotensin I-converting
      enzyme (ACE). However, the relationship between the ACE inhibitor and its in vivo
      action has revealed discrepancies. Therefore, the aim of the present study was to
      investigate the antihypertensive and heart rate (HR)-lowering effect of milk
      fermented by specific L. lactis in a murine model. Spontaneously hypertensive
      male rats (271 (SD14) g) were randomised into four treatment groups that were
      orally administered with milk fermented by L. lactis NRRL B-50 571 or L. lactis
      NRRL B-50 572 at 35 or 50 mg protein/kg body weight (BW), respectively. Further,
      two more groups were fed with different solutions as controls: a saline solution
      as the negative control and Captopril (40 mg/kg BW), a proven ACE inhibitor, as
      the positive control. Blood pressure and HR were monitored by the tail-cuff
      method before the treatments and at 2, 4, 6 and 24 h post-oral administration.
      The results demonstrated that milk fermented by L. lactis NRRL B-50 571 as well
      as by L. lactis NRRL B-50 572 presented an important systolic and diastolic blood
      pressure- and HR-lowering effect. Thus, milk fermented by specific L. lactis
      strains may present potential benefits in the prevention and treatment of CVD
      associated with hypertension in humans.

PMID- 23168231
TI  - Automated DNA extraction platforms offer solutions to challenges of assessing
      microbial biofouling in oil production facilities.
AB  - The analysis of microbial assemblages in industrial, marine, and medical systems
      can inform decisions regarding quality control or mitigation. Modern molecular
      approaches to detect, characterize, and quantify microorganisms provide rapid and
      thorough measures unbiased by the need for cultivation. The requirement of timely
      extraction of high quality nucleic acids for molecular analysis is faced with
      specific challenges when used to study the influence of microorganisms on oil
      production. Production facilities are often ill equipped for nucleic acid
      extraction techniques, making the preservation and transportation of samples off
      site a priority. As a potential solution, the possibility of extracting nucleic
      acids on-site using automated platforms was tested. The performance of two such
      platforms, the Fujifilm QuickGene-Mini80TM and Promega Maxwell(r)16 was compared
      to a widely used manual extraction kit, MOBIO PowerBiofilmTM DNA Isolation Kit,
      in terms of ease of operation, DNA quality, and microbial community composition.
      Three pipeline biofilm samples were chosen for these comparisons; two contained
      crude oil and corrosion products and the third transported seawater. Overall, the
      two more automated extraction platforms produced higher DNA yields than the
      manual approach. DNA quality was evaluated for amplification by quantitative PCR
      (qPCR) and end-point PCR to generate 454 pyrosequencing libraries for 16S rRNA
      microbial community analysis. Microbial community structure, as assessed by DGGE
      analysis and pyrosequencing, was comparable among the three extraction methods.
      Therefore, the use of automated extraction platforms should enhance the
      feasibility of rapidly evaluating microbial biofouling at remote locations or
      those with limited resources.

PMID- 23168232
TI  - Explaining and predicting individually experienced liking of berry fractions by
      the hTAS2R38 taste receptor genotype.
AB  - The roles of taste and astringent properties, food choice motives and health
      concerns in liking of bilberry and crowberry samples were studied using a sensory
      panel prescreened for the hTAS2R38 taste receptor genotype. The subjects rated
      the intensity of sourness, bitterness and two astringent properties (soft,
      velvety and rough, puckering) of all berry samples. They also scored the liking
      of juice fractions and completed a food choice motive and health concern
      questionnaire. Regression models were used to combine different data sets and to
      predict liking of the extracts. Sourness contributed positively to the liking of
      berry fractions, and bitterness and rough astringency were negative factors. The
      hTAS2R38 genotype affected the liking of polyphenol-rich extracts, which were
      significantly bitter and astringent. Based on the genotype grouping of subjects,
      PAV homozygotes gave lower ratings to the attributes than AVI homozygotes. In
      contrast, PAV homozygotes were predicted to dislike the extracts notably more
      than AVI homozygotes. Health concern and food choice motives related to health
      and weight control had significant roles in individual liking of juice fractions.
      Our results indicate that mood was more important to the PAV homozygotes than to
      the AVI homozygotes.

PMID- 23168233
TI  - Direct measurement of dissolved N2 and denitrification along a subtropical river
      estuary gradient, China.
AB  - The spatial pattern and seasonal variation of denitrification were investigated
      during 2010-2011 in the Jiulong River Estuary (JRE) in southeast China. Dissolved
      N2 was directly measured by changes in the N2:Ar ratio. The results showed that
      excess dissolved N2 ranged from -9.9 to 76.4 MUmol L-1. Tidal mixing leads to a
      seaward decline of dissolved gaseous concentrations and water-air fluxes along
      the river-estuary gradient. Denitrification at freshwater sites varied between
      seasons, associated with changes in N input and water temperature. The
      denitrification process was controlled by the nitrate level at freshwater sites,
      and the excess dissolved N2 observed at the tidal zone largely originated from
      upstream water transport. Compared to other estuaries, JRE has a relative low
      gaseous removal efficiency (E(d)=12% of [DIN]; annual N removal=24% of DIN load),
      a fact ascribed to strong tidal mixing, coarse-textured sediment with shallow
      depth before bedrock and high riverine DIN input.

PMID- 23168234
TI  - Responses of B-esterase enzymes in oysters (Crassostrea gigas) transplanted to
      pesticide contaminated bays form the Ebro Delta (NE, Spain).
AB  - Marine bivalves such as oysters are widely used as bioindicators to monitor
      marine coastal pollution. This study aimed to use B-esterase activity responses
      in oysters (Crassostrea gigas) cultured in Ebro Delta bays to monitor
      environmental effects of pesticides. The B esterases investigated were
      acetylcholinesterase, propionylcholinesterase, and carboxylesterase and their
      activities were measured in adductor muscle and gills from oysters transplanted
      in Ebro Delta bays where the are traditionally grown. Enzyme activities were
      related with physico-chemical parameters and pesticide levels measured in water.
      Cholinesterase activities measured in gills were unaffected across sites and
      periods. Conversely, carboxylesterase activities in oyster gills varied across
      periods and sites and were negatively correlated with residue levels of
      organophoshporous and carbamate pesticides in water. Therefore, inhibition of
      carboxylesterase activities can be considered a good indicator of exposure to
      anti-cholinergic pesticides in oysters.

PMID- 23168235
TI  - Treat-to-target in rheumatoid arthritis: clinical and pharmacoeconomic
      considerations. Introduction.

PMID- 23168236
TI  - DARC (Duffy) and BCAM (Lutheran) reduced expression in thyroid cancer.
AB  - Duffy or DARC (Duffy Antigen Receptor for Chemokines) is a glycosylated membrane
      protein that selectively binds angiogenic chemokines. Previous in vivo and in
      vitro studies of DARC function in cancer have associated DARC over expression
      with better prognosis, decreased metastatic potential, and inhibition of tumor
      associated neovascularization. Another carcinogenesis-associated antigen is
      Lutheran or BCAM (basal cell adhesion molecule), a surface glycoprotein that acts
      as a receptor for the extracellular matrix protein, laminin. BCAM is a protein
      related to tumor progression; and, its over expression is associated with skin,
      ovarian and pancreatic cancers. We explored DARC and BCAM functions and
      investigated whether or not their expressions were altered in thyroid cancer. The
      expression of DARC and BCAM were evaluated by quantitative real-time PCR (qPCR)
      in a set of 18 normal thyroid tissues (NT), 15 follicular adenomas (FTA), 17
      follicular carcinomas (FTC), and 122 papillary thyroid carcinomas (PTC),
      including 78 classical (CVPTC) and 44 follicular variant (FVPTC). RNA was
      isolated, reverse transcribed to cDNA, and used in qPCR reactions containing SYBR
      Green. The relative expression value was calculated using ribosomal protein S8 as
      an internal control. When we compared benign (NT and FTA) versus malignant
      samples (FTC, CVPTC and FVPTC) we observed a significant decrease of DARC and
      BCAM relative expression in malignant cases. Additionally, we correlated clinic
      pathological features (tumor size, presence of metastasis, presence of lymphocyte
      infiltrate) with DARC and BCAM expression. We found a diminished expression of
      DARC in PTC samples, which was correlated with tumor size and presence of a
      lymphocyte infiltrate. We, also, found a correlation between decreased BCAM
      expression and tumor size or presence of metastasis. DARC and BCAM expression was
      associated with pathogenesis of thyroid carcinoma and correlated with clinical
      pathological features.

PMID- 23168237
TI  - Hepatic cytokine response can be modulated using the Kupffer cell blocker
      gadolinium chloride in obstructive jaundice.
AB  - INTRODUCTION: Depletion of Kupffer cells by gadolinium chloride (GdCl(3)) reduces
      the systemic response during sepsis. The study aim was to investigate the effect
      of this depletion on hepatic proinflammatory cytokine response to portal
      endotoxaemia. METHODS: Sixteen Wistar rats were randomised to receive either
      saline IV (n = 8) or GdCl(3) (10 mg/kg IV, n = 8) six days after bile duct
      ligation (BDL). 24 h later the animals were perfused for 2 h, using isolated
      hepatic perfusion. Aliquots of effluent perfusate were collected at 20-min
      intervals for cytokine analysis. Sections of liver were sampled and the hepatic
      Kupffer cell number of each group was measured using ED1 immunohistochemistry.
      RESULTS: Pre-treatment with GdCl(3) resulted in significantly reduced serum
      bilirubin concentrations but significantly elevated serum ALP and AST levels
      compared to the control group. It was also associated with a significant
      reduction in Kupffer cell numbers and a corresponding significant reduction in
      hepatic TNFalpha and IL-6 production in response to portal endotoxaemia.
      CONCLUSIONS: Pre-treatment with GdCl(3) in jaundiced animals reduced Kupffer cell
      numbers, attenuated liver enzyme abnormalities and reduced TNFalpha and IL-6 in
      response to portal endotoxaemia. Hepatic Kupffer cells, therefore, play a
      significant role in the development of an exaggerated inflammatory response in
      obstructive jaundice.

PMID- 23168239
TI  - Fatty acid composition of wild mushroom species of order Agaricales--examination
      by gas chromatography-mass spectrometry and chemometrics.
AB  - Applying gas chromatography-mass spectrometry of 4,4-dimethyloxazoline fatty acid
      derivatives, the fatty acid composition of 15 mushroom species belonging to 9
      genera and 5 families of order Agaricales growing in Bulgaria is determined. The
      structure of 31 fatty acids (not all present in each species) is unambiguously
      elucidated, with linoleic, oleic and palmitic acids being the main components
      (ranging between 70.9% (Marasmius oreades) and 91.2% (Endoptychum agaricoides)).
      A group of three hexadecenoic positionally isomeric fatty acids, 6-, 9- and 11
      16:1, appeared to be characteristic components of the examined species. By
      applying chemometrics it was possible to show that the fatty acid composition
      closely reflects the classification of the species.

PMID- 23168240
TI  - Application of the Vibrant Soundbridge middle-ear implant for aural atresia in
      patients with Treacher Collins syndrome.
AB  - OBJECTIVE: To present results for the auditory rehabilitation of patients with
      Treacher Collins syndrome with bilateral osseous atresia, using middle-ear
      implantation with a Vibrant Soundbridge. METHODS: Three patients underwent
      vibroplasty for aural atresia with moderate to severe conductive hearing loss.
      The pre-operative Jahrsdoerfer radiological score was 4 for all patients.
      Patients underwent active middle-ear implantation of a Vibrant Soundbridge
      implant (coupling the floating mass transducer to the rudimentary stapes or
      footplate distally, and positioning it adjacent to the round window membrane
      proximally), with audiological analysis as follow up. RESULTS: After implant
      activation, the mean air conduction threshold +/- standard deviation decreased to
      22.8 +/- 5.5 dB HL, representing a mean functional gain of 44.5 dB. The mean word
      recognition score (for bisyllabic words at 65 dB SPL) increased from 0 to 97 per
      cent. CONCLUSION: Vibrant Soundbridge implantation is an effective hearing
      rehabilitation procedure in patients with Treacher Collins syndrome with
      bilateral osseous atresia. This is a versatile implant which can achieve coupling
      even in cases of severe middle-ear malformation.

PMID- 23168241
TI  - Merit of quinacrine in the decrease of ingested sulfite-induced toxic action in
      rat brain.
AB  - We aimed at investigating the effects of sulfite-induced lipid peroxidation and
      apoptosis mediated by secretory phospholipase A2 (sPLA2) on somatosensory evoked
      potentials (SEP) alterations in rats. Thirty male albino Wistar rats were
      randomized into three experimental groups as follows; control (C), sodium
      metabisulfite treated (S), sodium metabisulfite+quinacrine treated (SQ). Sodium
      metabisulfite (100 mg/kg/day) was given by gastric gavage for 5 weeks and 10
      mg/kg/day quinacrine was applied as a single dose of intraperitoneal injection
      for the same period. The latencies of SEP components were significantly prolonged
      in the S group and returned to control levels following quinacrine
      administration. Plasma-S-sulfonate level was increased in S and SQ groups. TBARS
      levels in the S group were significantly higher than those detected in controls.
      Quinacrine significantly decreased brain TBARS levels in the SQ group compared
      with the S group. Quinacrine treatment did not have an effect on the increased
      sPLA2 level of the sulfite administered group. Immunohistochemistry showed that
      sulfite caused an increase in caspase-3 and TUNEL positive cells, restored to
      control levels via quinacrine administration. This study showed that sPLA2 might
      play a role in ingested sulfite-induced SEP alterations, oxidative stress,
      apoptotic cell death and DNA damage in the brain.

PMID- 23168242
TI  - Investigation of the neuroprotective action of saffron (Crocus sativus L.) in
      aluminum-exposed adult mice through behavioral and neurobiochemical assessment.
AB  - In the present study, the possible reversal effects of saffron against
      established aluminum (Al)-toxicity in adult mice, were investigated. Control, Al
      treated (50 mg AlCl(3)/kg/day diluted in the drinking water for 5 weeks) and
      Al+saffron (Al-treatment as previously plus 60 mg saffron extract/kg/day
      intraperitoneally for the last 6 days), groups of male Balb-c mice were used. We
      assessed learning/memory, the activity of acetylcholinesterase [AChE, salt
      (SS)/detergent-soluble(DS) isoforms], butyrylcholinesterase (BuChE, SS/DS
      isoforms), monoamine oxidase (MAO-A, MAO-B), the levels of lipid peroxidation
      (MDA) and reduced glutathione (GSH), in whole brain and cerebellum. Brain Al was
      determined by atomic absorption spectrometry, while, for the first time,
      crocetin, the main active metabolite of saffron, was determined in brain after
      intraperitoneal saffron administration by HPLC. Al intake caused memory
      impairment, significant decrease of AChE and BuChE activity, activation of brain
      MAO isoforms but inhibition of cerebellar MAO-B, significant elevation of brain
      MDA and significant reduction of GSH content. Although saffron extract co
      administration had no effect on cognitive performance of mice, it reversed
      significantly the Al-induced changes in MAO activity and the levels of MDA and
      GSH. AChE activity was further significantly decreased in cerebral tissues of
      Al+saffron group. The biochemical changes support the neuroprotective potential
      of saffron under toxicity.

PMID- 23168243
TI  - Duplication of chromosome 1 [dup(1)(q21q32)] as the sole cytogenetic abnormality
      in a patient previously treated for AML.
AB  - A nonrandom structural gain of 1q may be seen in myelodysplastic syndrome (MDS)
      and acute myeloid leukemia (AML), and often it is due to an unbalanced
      translocation. Dup(1)(q21q32) as the sole abnormality has only rarely been
      reported. Reports have suggested that the dup(1)(q21q32) is predictive of a poor
      prognosis. We describe a case report of a 55 year old male who presented in 2002
      with AML-M2, t(8;21)(q22;q22). He underwent induction with "7+3" followed by
      consolidation chemotherapy resulting in a complete remission. Two years later,
      his bone marrow revealed a dup(1)(q21q32) as an isolated aberration for the first
      time. In 2010, cytogenetic analysis of the bone marrow again confirmed this
      finding and FISH for AML1/ETO t(8;21) remained negative. Dup(1q) developed as an
      isolated abnormality two years after AML treatment, and to date, there is no
      evidence of progression to MDS. This is the first report of an acquired
      dup(1)(q21q32) as the sole abnormality in a patient treated for AML. This
      suggests that the dup(1q) may not be exclusively associated with a poor
      prognosis.

PMID- 23168244
TI  - Vitamin D in pregnancy at high latitude in Scotland.
AB  - The aims of the present study were to determine compliance with current advice on
      vitamin D and to assess the influence of season, dietary intake, supplement use
      and deprivation on vitamin D status in pregnant mothers and newborns in the north
      of Scotland where sunlight exposure is low. Pregnant women (n 1205) and their
      singleton newborns were studied in the Aberdeen Maternity Hospital (latitude 57
      degrees N) between 2000 and 2006. Plasma 25-hydroxyvitamin D2 and 25
      hydroxyvitamin D3 were measured at 19 weeks of gestation in mothers and at
      delivery in newborns. During pregnancy, 21.0 (95 % CI 18.5, 23.5) % of women took
      vitamin D supplements. The median intake was 5 MUg/d and only 0.6 (95 % CI 0.1,
      1.0) % took the recommended 10 MUg/d. Supplement use, adjusted for season,
      dietary intake and deprivation, significantly increased maternal 25
      hydroxyvitamin D (25(OH)D) by 10.5 (95 % CI 5.7, 15.2) nmol/l (P< 0.001);
      however, there was no significant effect on cord 25(OH)D (1.4 (95 % CI - 1.8,
      4.5) nmol/l). The biggest influence on both maternal and cord 25(OH)D was season
      of birth (P< 0.001). Compared with the least deprived women (top three deciles),
      the most deprived pregnancies (bottom three deciles) were characterised by a
      significantly lower seasonally adjusted 25(OH)D ( - 11.6 (95 % CI - 7.5, - 15.7)
      nmol/l in the mother and - 5.8 (95 % CI - 2.3, - 9.4) nmol/l in the cord), and a
      lower level of supplement use (10 (95 % CI 4, 17) v. 23 (95 % CI 20, 26) %). More
      should be done to promote vitamin D supplement use in pregnancy but the critical
      importance of endogenous vitamin D synthesis, and known adaptations of fat
      metabolism specific to pregnancy, suggest that safe sun advice may be a useful
      additional strategy, even at high latitude.

PMID- 23168245
TI  - Neuron-restrictive silencer factor functions to suppress Sp1-mediated
      transactivation of human secretin receptor gene.
AB  - In the present study, a functional neuron restrictive silencer element (NRSE) was
      initially identified in the 5' flanking region (-83 to -67, relative to ATG) of
      human secretin receptor (hSCTR) gene by promoter assays coupled with scanning
      mutation analyses. The interaction of neuron restrictive silencer factor (NRSF)
      with this motif was later indicated via gel mobility shift and ChIP assays. The
      silencing activity of NRSF was confirmed by over-expression and also by shRNA
      knock-down of endogenous NRSF. These studies showed an inverse relationship
      between the expression levels of NRSF and hSCTR in the cells. As hSCTR gene was
      previously shown to be controlled by two GC-boxes which are regulated by the
      ratio of Sp1 to Sp3, in the present study, the functional interactions of NRSF
      and Sp proteins to regulate hSCTR gene was investigated. By co
      immunoprecipitation assays, we found that NRSF could be co-precipitated with Sp1
      as well as Sp3 in PANC-1 cells. Interestingly, co-expressions of these factors
      showed that NRSF could suppress Sp1-mediated, but not Sp3-mediated,
      transactivation of hSCTR. Taken together, we propose here that the down
      regulatory effects of NRSF on hSCTR gene expression are mediated via its
      suppression on Sp1-mediated transactivation.

PMID- 23168246
TI  - Fatty acid profiling of tropical marine macroalgae: an analysis from
      chemotaxonomic and nutritional perspectives.
AB  - The lipid and fatty acid (FA) compositions for 100 marine macroalgae were
      determined and discussed from the context of chemotaxonomic and nutritional
      perspectives. In general, the lipid contents in macroalgae were low (2.3-20 mg/g
      fr. wt.) but with substantially high amounts of nutritionally important
      polyunsaturated fatty acids (PUFAs) such as LA, ALA, STA, AA, EPA and DHA, that
      ranged from 10% to 70% of TFAs. More than 90% of the species showed nutritionally
      beneficial n6/n3 ratio (0.1:1-3.6:1) (p<=0.001). A closer look at the FA data
      revealed characteristic chemotaxonomic features with C18 PUFAs (LA, ALA and STA)
      being higher in Chlorophyta, C20 PUFAs (AA and EPA) in Rhodophyta while
      Phaeophyta depicted evenly distribution of C18 and C20 PUFAs. The ability of
      macroalgae to produce long-chain PUFAs could be attributed to the coupling of
      chloroplastic FA desaturase enzyme system from a photosynthetic endosymbiont to
      the FA desaturase/elongase enzyme system of a non-photosynthetic eukaryotic
      protist host. Further, the principal component analysis segregated the three
      macroalgal groups with a marked distinction of different genera, families and
      orders, Hierarchical cluster analyses substantiated the phylogenetic
      relationships of all orders investigated except for those red algal taxa
      belonging to Gigartinales, Ceramiales, Halymeniales and Rhodymeniales for which
      increased sampling effort is required to infer a conclusion. Also, the groups
      deduced from FA compositions were congruent with the clades inferred from nuclear
      and plastid genome sequences. This study further indicates that FA signatures
      could be employed as a valid chemotaxonomic tool to differentiate macroalgae at
      higher taxonomic levels such as family and orders.

PMID- 23168247
TI  - Filamentous fungi from Plantago lanceolata L. leaves: contribution to the pattern
      and stability of bioactive metabolites.
AB  - The aim of this study was to test contribution of plant-associated microorganism
      (PAMs) to metabolite stability/instability in a medicinal plant matrix.
      Therefore, PAM strains were isolated and identified based on relevant DNA
      sequences from Plantago lanceolata leaves. Sterile water extracts of P.
      lanceolata were incubated with the isolated strains and antioxidants (ascorbic
      acid (AA), and EDTA) for 15 days, and changes in the concentrations of chief
      bioactive constituents (aucubin, catalpol, acteoside (=verbascoside)) were
      quantified by capillary electrophoresis. Phenolic breakdown-products were
      identified by GC-MS. PAMs were identified from the genera Epicoccum, Bipolaris,
      Cladosporium, Leptosphaerulina, Aspergillus, Eurotium and Penicillium
      (pathongens, endophytes, and other species). Some fungi caused significant
      decomposition of the chief constituents (p<0.001). Surprisingly, some strains
      inhibited breakdown of acteoside (p<0.001). Meanwhile, concentration of several
      phenolic acids increased in fungi-infested extracts (p<0.001). Gentisic acid, 4
      hydroxyphenyl acetic acid, 4-hydroxybenzoic acid and hydroxytyrosol were only
      present when the extract was infested with a PAM. The products are powerful
      antioxidants and chelators. Concentrations of phenolic acids influenced acteoside
      stability significantly (p<0.01), as shown by basic data-mining techniques. AA
      and EDTA also significantly inhibited acteoside breakdown in sterile model
      solutions (p<0.05). Our results suggest that the phenolic acid mixture (produced
      during the fungal proliferation) protected acteoside from breakdown, possibly via
      its antioxidant activity and metal complexing ability. It was shown that PAMs can
      increase or decrease the stability of chief metabolites in herbal matrices, and
      can significantly alter the chemical pattern of the plant matrix.

PMID- 23168248
TI  - Cerebral blood flow and glucose metabolism in healthy volunteers measured using a
      high-resolution PET scanner.
AB  - BACKGROUND: Positron emission tomography (PET) allows for the measurement of
      cerebral blood flow (CBF; based on [15O]H2O) and cerebral metabolic rate of
      glucose utilization (CMRglu; based on [18 F]-2-fluoro-2-deoxy-d-glucose ([18
      F]FDG)). By using kinetic modeling, quantitative CBF and CMRglu values can be
      obtained. However, hardware limitations led to the development of semiquantitive
      calculation schemes which are still widely used. In this paper, the analysis of
      CMRglu and CBF scans, acquired on a current state-of-the-art PET brain scanner,
      is presented. In particular, the correspondence between nonlinear as well as
      linearized methods for the determination of CBF and CMRglu is investigated. As a
      further step towards widespread clinical applicability, the use of an image
      derived input function (IDIF) is investigated. METHODS: Thirteen healthy male
      volunteers were included in this study. Each subject had one scanning session in
      the fasting state, consisting of a dynamic [15O]H2O scan and a dynamic [18 F]FDG
      PET scan, acquired at a high-resolution research tomograph. Time-activity curves
      (TACs) were generated for automatically delineated and for manually drawn gray
      matter (GM) and white matter regions. Input functions were derived using on-line
      arterial blood sampling (blood sampler derived input function (BSIF)).
      Additionally, the possibility of using carotid artery IDIFs was investigated.
      Data were analyzed using nonlinear regression (NLR) of regional TACs and
      parametric methods. RESULTS: After quality control, 9 CMRglu and 11 CBF scans
      were available for analysis. Average GM CMRglu values were 0.33 +/- 0.04
      MUmol/cm3 per minute, and average CBF values were 0.43 +/- 0.09 mL/cm3 per
      minute. Good correlation between NLR and parametric CMRglu measurements was
      obtained as well as between NLR and parametric CBF values. For CMRglu Patlak
      linearization, BSIF and IDIF derived results were similar. The use of an IDIF,
      however, did not provide reliable CBF estimates. CONCLUSION: Nonlinear regression
      analysis, allowing for the derivation of regional CBF and CMRglu values, can be
      applied to data acquired with high-spatial resolution current state-of-the-art
      PET brain scanners. Linearized models, applied to the voxel level, resulted in
      comparable values. CMRglu measurements do not require invasive arterial sampling
      to define the input function. TRIAL REGISTRATION: ClinicalTrials.gov NCT00626080.

PMID- 23168249
TI  - 'Conchae bullosis': a rare case with bilateral triple turbinate pneumatisations.
AB  - BACKGROUND: Concha bullosa is the pneumatisation of intranasal conchae (usually
      the middle turbinate, and rarely the inferior or superior turbinate); however,
      the term is generally used to describe aeration of the middle concha. Superior
      concha bullosa is a rare finding, and only a few cases of inferior concha bullosa
      have been reported in the medical literature. When symptomatic, concha bullosa
      may cause various problems including nasal congestion, headache, postnasal drip,
      anosmia and, sometimes, epiphora. METHODOLOGY: Computed tomography, following
      history-taking and physical examination, is a valuable tool in diagnosing
      turbinate pneumatisation. This article presents a very rare case with bilateral
      triple conchae pneumatisations. RESULTS: The symptomatology, diagnosis and
      treatment options for cases of multiple concha bullosa are discussed. The
      surgical interventions performed in the presented case are briefly described.
      CONCLUSION: The presented patient had pneumatisation of all six turbinates. In
      such cases, we propose that this condition be termed 'conchae bullosis' rather
      than 'conchae bullosa', in a similar fashion to the use of nasal polyposis as the
      plural form of nasal polyp.

PMID- 23168250
TI  - Serum vitamin B12 not reflecting vitamin B12 status in patients with type 2
      diabetes.
AB  - Contradictory results for concentrations of vitamin B12, holotranscobalamin
      (holoTC), and methylmalonic acid (MMA) have been reported. We tested the
      hypothesis that the extracellular vitamin B12 markers are not reflecting the
      intracellular vitamin B12-dependent biochemical reactions in individuals with
      type 2 diabetes. The study included 92 patients with diabetes and 72 controls
      with similar age and sex distribution. We measured vitamin B12 markers [MMA,
      total serum vitamin B12, holoTC, total homocysteine (tHcy)], red blood cell (RBC)
      B12, and the plasma concentrations of the methylation markers [S
      adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH)]. In comparison to
      controls, diabetic patients showed significantly higher concentrations of plasma
      SAH (median 15.1 vs. 11.8 nmol/L; p < 0.001) and lower SAM/SAH ratio (9.1 vs.
      8.2; p = 0.006). Concentrations of total vitamin B12 and holoTC did not differ
      significantly between the groups, but plasma MMA concentrations were
      significantly higher in diabetics (250 vs. 206 nmol/L). However, RBC-B12 was
      lower in diabetics compared to controls (median 230 vs. 260 pmol/L; p = 0.001).
      The inverse correlation between MMA and RBC-B12 was stronger in the controls
      compared to that in the patients (correlation coefficient in controls R = -0.446,
      p = 0.001; in patients R = -0.289, p = 0.022). Metformin treatment was associated
      with a lower total serum vitamin B12, but a comparable RBC-B12 and a slightly
      lower MMA and better methylation index. In conclusion, patients with type 2
      diabetes showed normal extracellular vitamin B12, but disturbed intracellular B12
      dependent biochemical reactions. Metformin treatment was associated with low
      serum vitamin B12 and improved intracellular vitamin B12 metabolism despite low
      serum vitamin B12.

PMID- 23168251
TI  - An experimental test of voluntary strategies to promote urban water demand
      management.
AB  - In light of the current and future threats to global water security the current
      research focuses on trialing interventions to promote urban water conservation.
      We report an experimental study designed to test the long-term impact of three
      different interventions on household water consumption in South East Queensland.
      Participants from 221 households were recruited and completed an initial survey,
      and their houses were fitted with smart water meters which measured total water
      usage at 5 s intervals. Households were allocated into one of four conditions: a
      control group and three interventions groups (water saving information alone,
      information plus a descriptive norm manipulation, and information plus tailored
      end-user feedback). The study is the first to use smart water metering technology
      as a tool for behaviour change as well as a way to test the effectiveness of
      demand management interventions. Growth curve modelling revealed that compared to
      the control, the three intervention groups all showed reduced levels of household
      consumption (an average reduction of 11.3 L per person per day) over the course
      of the interventions, and for some months afterwards. All interventions led to
      significant water savings, but long-term household usage data showed that in all
      cases, the reduction in water use resulting from the interventions eventually
      dissipated, with water consumption returning to pre-intervention levels after
      approximately 12 months. Implications for water demand management programs are
      discussed.

PMID- 23168252
TI  - Critical factors for EIA implementation: literature review and research options.
AB  - After decades of development, the gap between expectations of Environment Impact
      Assessments (EIA) and their practical performance remains significant. Research
      has been done to identify the critical factors for an effective implementation of
      EIA. However, this research, to a large extent, has not been cumulated and
      analysed comprehensively according to the stages of the EIA process. This paper
      contributes to the critical review of the literature on EIA implementation and
      effectiveness by cumulating mainly empirical findings in an implementation
      theoretical perspective. It focuses on the links between different critical
      factors and how they relate to different stages in the EIA and thus influence the
      decision making process. After reviewing 33 refereed journal articles published
      between 1999 and 2011, we identified 203 notions of critical factors. Of these,
      102 related to different stages defined in our comprehensive EIA implementation
      model, and 101 were identified as general factors related to the whole EIA
      system. The number of notions of stage factors and general factors is thus about
      equal. An overlap between stage factors and general factors was found, which
      demonstrates that critical factors function differently in different cases. The
      function of the critical factors is complex and it is difficult to determine
      contingencies and causations. In the sources we examined, there is evidently an
      imbalance between in-depth empirical research and general knowledge, and the
      paper offers some suggestions for future research.

PMID- 23168253
TI  - Scenario analysis of the benefit of municipal organic-waste composting over
      landfill, Cambodia.
AB  - This paper presents insight into the benefits of organic waste recycling through
      composting over landfill, in terms of landfill life extension, compost product,
      and mitigation of greenhouse gases (GHGs). Future waste generation from 2003 to
      2020 was forecast, and five scenarios of organic waste recycling in the
      municipality of Phnom Penh (MPP), Cambodia, were carried out. Organic waste
      specifically food and garden waste-was used for composting, and the remaining
      waste was landfilled. The recycling scenarios were set based on organic waste
      generated from difference sources: households, restaurants, shops, markets,
      schools, hotels, offices, and street sweeping. Through the five scenarios, the
      minimum volume reductions of waste disposal were about 56, 123, and 219 m(3) d(
      1) in 2003, 2012, and 2020, respectively, whereas the maximum volume reductions
      in these years were about 325, 643, and 1025 m(3) d(-1). These volume reductions
      reflect a landfill life extension of a minimum of half a year and a maximum of
      about four years. Compost product could be produced at a minimum of 14, 30, and
      54 tons d(-1) in 2003, 2012, and 2020, respectively, and at a maximum in those
      years of about 80, 158, and 252 tons d(-1). At the same time benefit is gained in
      compost product, GHG emissions could be reduced by a minimum of 12.8% and a
      maximum of 65.0% from 2003 to 2020. This means about 3.23 (minimum) and 5.79
      million tons CO(2)eq (maximum) contributed to GHG mitigation. In this regard, it
      is strongly recommended that MPP should try to initiate an organic-waste
      recycling strategy in a best fit scenario.

PMID- 23168254
TI  - Regional differences in overweight rates: the case of Italian regions.
AB  - Southern regions in Italy are characterized by higher overweight rates than
      Northern and Central regions. This gap is higher for young males than for
      females. We fully account for the differences in overweight rates with a
      relatively parsimonious set of covariates, and show that the key factors
      accounting for these differences vary substantially by gender. There is a strong
      association between regional differences in educational attainment, labor market
      outcomes and overweight rates for females, and a strong association between
      regional differences in parental and peer BMI, the regional percentage of primary
      schools with a canteen and overweight rates for males. We are grateful to two
      anonymous referees and to Danilo Cavapozzi for help with the data. Financial
      support by Fondazione Cariparo is gratefully acknowledged. The usual disclaimer
      applies. 

PMID- 23168255
TI  - Effects of feeding Bt MON810 maize to sows during first gestation and lactation
      on maternal and offspring health indicators.
AB  - A total of twenty-four sows and their offspring were used in a 20-week study to
      investigate the effects of feeding GM maize on maternal and offspring health.
      Sows were fed diets containing GM or non-GM maize from service to the end of
      lactation. GM maize-fed sows were heavier on day 56 of gestation (P< 0.05).
      Offspring from sows fed GM maize tended to be lighter at weaning (P= 0.08). Sows
      fed GM maize tended to have decreased serum total protein (P= 0.08), and
      increased serum creatinine (P< 0.05) and gamma-glutamyltransferase activity (P=
      0.07) on day 28 of lactation. Serum urea tended to be decreased on day 110 of
      gestation in GM maize-fed sows (P= 0.10) and in offspring at birth (P= 0.08).
      Both platelet count (P= 0.07) and mean cell Hb concentration (MCHC; P= 0.05) were
      decreased on day 110 of gestation in GM maize-fed sows; however, MCHC tended to
      be increased in offspring at birth (P= 0.08). There was a minimal effect of
      feeding GM maize to sows during gestation and lactation on maternal and offspring
      serum biochemistry and haematology at birth and body weight at weaning.

PMID- 23168256
TI  - T cell activation is driven by an ADP-dependent glucokinase linking enhanced
      glycolysis with mitochondrial reactive oxygen species generation.
AB  - Mitochondria-originating reactive oxygen species (ROS) control T cell receptor
      (TCR)-induced gene expression. Here, we show that TCR-triggered activation of ADP
      dependent glucokinase (ADPGK), an alternative, glycolytic enzyme typical for
      Archaea, mediates generation of the oxidative signal. We also show that ADPGK is
      localized in the endoplasmic reticulum and suggest that its active site protrudes
      toward the cytosol. The ADPGK-driven increase in glycolytic metabolism coincides
      with TCR-induced glucose uptake, downregulation of mitochondrial respiration, and
      deviation of glycolysis toward mitochondrial glycerol-3-phosphate
      dehydrogenase(GPD) shuttle; i.e., a metabolic shift to aerobic glycolysis similar
      to the Warburg effect. The activation of respiratory-chain-associated GPD2
      results in hyperreduction of ubiquinone and ROS release from mitochondria. In
      parallel, mitochondrial bioenergetics and ultrastructure are altered.
      Downregulation of ADPGK or GPD2 abundance inhibits oxidative signal generation
      and induction of NF-kappaB-dependent gene expression, whereas overexpression of
      ADPGK potentiates them.

PMID- 23168258
TI  - Coding odorant concentration through activation timing between the medial and
      lateral olfactory bulb.
AB  - In mammals, each olfactory bulb (OB) contains a pair of mirror-symmetric
      glomerular maps organized to reflect odorant receptor identity. The functional
      implication of maintaining these symmetric medial-lateral maps within each OB
      remains unclear. Here, using in vivo multielectrode recordings to simultaneously
      detect odorant-induced activity across the entire OB, we reveal a timing
      difference in the odorant-evoked onset latencies between the medial and lateral
      halves. Interestingly, the latencies in the medial and lateral OB decreased at
      different rates as odorant concentration increased, causing the timing difference
      between them to also diminish. As a result, output neurons in the medial and
      lateral OB fired with greater synchrony at higher odorant concentrations. Thus,
      we propose that temporal differences in activity between the medial and lateral
      OB can dynamically code odorant concentration, which is subsequently decoded in
      the olfactory cortex through the integration of synchronous action potentials.

PMID- 23168259
TI  - On the expansion of "dangerous" gene repertoires by whole-genome duplications in
      early vertebrates.
AB  - The emergence and evolutionary expansion of gene families implicated in cancers
      and other severe genetic diseases is an evolutionary oddity from a natural
      selection perspective. Here, we show that gene families prone to deleterious
      mutations in the human genome have been preferentially expanded by the retention
      of "ohnolog" genes from two rounds of whole-genome duplication (WGD) dating back
      from the onset of jawed vertebrates. We further demonstrate that the retention of
      many ohnologs suspected to be dosage balanced is in fact indirectly mediated by
      their susceptibility to deleterious mutations. This enhanced retention of
      "dangerous" ohnologs, defined as prone to autosomal-dominant deleterious
      mutations, is shown to be a consequence of WGD-induced speciation and the ensuing
      purifying selection in post-WGD species. These findings highlight the importance
      of WGD-induced nonadaptive selection for the emergence of vertebrate complexity,
      while rationalizing, from an evolutionary perspective, the expansion of gene
      families frequently implicated in genetic disorders and cancers.

PMID- 23168260
TI  - JMJD2A promotes cellular transformation by blocking cellular senescence through
      transcriptional repression of the tumor suppressor CHD5.
AB  - Senescence is a cellular response preventing tumorigenesis. The Ras oncogene is
      frequently activated or mutated in human cancers, but Ras activation is
      insufficient to transform primary cells. In a search for cooperating oncogenes,
      we identify the lysine demethylase JMJD2A/KDM4A. We show that JMJD2A functions as
      a negative regulator of Ras-induced senescence and collaborates with oncogenic
      Ras to promote cellular transformation by negatively regulating the p53 pathway.
      We find CHD5, a known tumor suppressor regulating p53 activity, as a target of
      JMJD2A. The expression of JMJD2A inhibits Ras-mediated CHD5 induction leading to
      a reduced activity of the p53 pathway. In addition, we show that JMJD2A is
      overexpressed in mouse and human lung cancers. Depletion of JMJD2A in the human
      lung cancer cell line A549 bearing an activated K-Ras allele triggers senescence.
      We propose that JMJD2A is an oncogene that represents a target for Ras-expressing
      tumors.

PMID- 23168257
TI  - Cellular strategies for regulating functional and nonfunctional protein
      aggregation.
AB  - Growing evidence suggests that aggregation-prone proteins are both harmful and
      functional for a cell. How do cellular systems balance the detrimental and
      beneficial effect of protein aggregation? We reveal that aggregation-prone
      proteins are subject to differential transcriptional, translational, and
      degradation control compared to nonaggregation-prone proteins, which leads to
      their decreased synthesis, low abundance, and high turnover. Genetic modulators
      that enhance the aggregation phenotype are enriched in genes that influence
      expression homeostasis. Moreover, genes encoding aggregation-prone proteins are
      more likely to be harmful when overexpressed. The trends are evolutionarily
      conserved and suggest a strategy whereby cellular mechanisms specifically
      modulate the availability of aggregation-prone proteins to (1) keep
      concentrations below the critical ones required for aggregation and (2) shift the
      equilibrium between the monomeric and oligomeric/aggregate form, as explained by
      Le Chatelier's principle. This strategy may prevent formation of undesirable
      aggregates and keep functional assemblies/aggregates under control.

PMID- 23168261
TI  - Enhancement of geraniol resistance of Escherichia coli by MarA overexpression.
AB  - Improvement of a microorganism's tolerance against organic solvents is required
      for a microbial factory producing terpenoid based biofuels. The bacterial genes,
      marA, imp, cls and cti have been found to increase organic solvent tolerance.
      Thus, the tolerance against the following terpenoids (isopentenol, geraniol,
      myrcene, and farnesol) was studied with overexpression of marA, imp, cls and cti
      genes in Escherichia coli. The marA overexpression significantly enhanced the
      tolerance of E. coli against geraniol, whereas there was no tolerance improvement
      against the terpenoids by overexpression of cls and cti genes. The imp
      overexpression even yielded sensitive phenotype to the tested solvents. The
      colony forming efficiency of the marA overexpressing E. coli was increased by
      10(4)-fold in plate overlay of geraniol compared to that of wild type E. coli and
      a two-fold decrease of intracellular geraniol accumulation was also observed in
      liquid culture of geraniol. Single knock-out mutations of marA, or one of the
      following genes (acrA, acrB and tolC) encoding AcrAB-TolC efflux pump made E.
      coli hypersensitive to geraniol. The geraniol tolerance conferred by marA
      overexpression was attributed to the AcrAB-TolC efflux pump that is activated by
      MarA.

PMID- 23168262
TI  - Environmental methicillin-resistant Staphylococcus aureus contamination in pig
      herds in relation to the productive phase and application of cleaning and
      disinfection.
AB  - The aim of the study is to better understand MRSA environmental contamination in
      pig holdings in relation to the productive phase and the application of
      environmental cleaning and disinfection practices (C&D). This study was carried
      out on six herds. Dust samples from farrowing crates, weaning boxes, growing and
      finishing pens were collected from each herd environment prior to and after C&D
      and cultured for MRSA. Ten samples were collected at the end of each productive
      phase with the animals present and 10 additional samples were collected after
      C&D, prior to introduction of a new stock. The proportion of positive samples
      prior to C&D was lower in fattening than in other phases. The proportion of
      positive samples prior to and after C&D was 121/240 (50%) and 46/240 (19%)
      respectively. In the mixed effects logistic regression analysis it was shown not
      only that both productive phase and C&D were associated with the probability of
      having a positive sample but also that the C&D effect was different in the
      different productive phases. In particular the effect of C&D was stronger in
      farrowing crates than in the other productive phases. The results of this study
      show that, although current practices of cleaning and disinfection reduce MRSA
      environmental contamination, they are likely to be inadequate to the elimination
      of the microorganism. However, a strict application of hygienic protocols can
      lead to a marked reduction of MRSA environmental contamination.

PMID- 23168263
TI  - Approaches to basal ganglia cavernomas.

PMID- 23168264
TI  - Differences in the prevalence of Tritrichomonas foetus infection in beef cattle
      farmed under extensive conditions in northern Spain.
AB  - Bovine trichomonosis (BT) is a sexually transmitted disease of cattle caused by
      infection with Tritrichomonas foetus. In a recent study, T. foetus infection was
      detected in 41.5% of herds of an endangered beef breed, the Asturiana de la
      Montana (AM), which is farmed under extensive, mountain pastoral systems in
      northern Spain. The objective of this study was to determine the prevalence of
      this pathogen in the more production-centred Asturiana de los Valles (AV) beef
      breed farmed in the same region, and to identify potential associated management
      risk factors. Infection was detected in a significantly smaller number (5.2%) of
      AV herds, despite the fact that both populations share the same ecological niche.
      Communal grazing was not identified as significant risk factor and study results
      suggest the prevalence of BT is likely to vary considerably depending on how the
      cattle are managed.

PMID- 23168265
TI  - Equine laminitis: what is all the hype about hyperinsulinaemic laminitis?

PMID- 23168267
TI  - Beyond steroidogenesis: novel target genes for SF-1 discovered by genomics.
AB  - Steroidogenic Factor-1 (SF-1) is a nuclear receptor transcription factor that has
      an essential role in the development of adrenal glands and gonads and in the
      regulation of steroidogenic gene expression. Recent studies using genomic
      approaches have revealed that SF-1 also has an important role in regulating
      proliferation of adrenocortical cells and have revealed its role in the control
      of a variety of biological processes as diverse as angiogenesis, adhesion to the
      extracellular matrix, cytoskeleton dynamics, transcriptional and post
      transcriptional regulation of gene expression and apoptosis in the adrenal
      cortex. The identification of the complete set of SF-1 target genes will be of
      great importance to open new avenues for therapeutic intervention in adrenal
      diseases.

PMID- 23168266
TI  - Epigenome remodelling in breast cancer: insights from an early in vitro model of
      carcinogenesis.
AB  - Epigenetic gene regulation has influence over a diverse range of cellular
      functions, including the maintenance of pluripotency, differentiation, and
      cellular identity, and is deregulated in many diseases, including cancer. Whereas
      the involvement of epigenetic dysregulation in cancer is well documented, much of
      the mechanistic detail involved in triggering these changes remains unclear. In
      the current age of genomics, the development of new sequencing technologies has
      seen an influx of genomic and epigenomic data and drastic improvements in both
      resolution and coverage. Studies in cancer cell lines and clinical samples using
      next-generation sequencing are rapidly delivering spectacular insights into the
      nature of the cancer genome and epigenome. Despite these improvements in
      technology, the timing and relationship between genetic and epigenetic changes
      that occur during the process of carcinogenesis are still unclear. In particular,
      what changes to the epigenome are playing a driving role during carcinogenesis
      and what influence the temporal nature of these changes has on cancer progression
      are not known. Understanding the early epigenetic changes driving breast cancer
      has the exciting potential to provide a novel set of therapeutic targets or early
      disease biomarkers or both. Therefore, it is important to find novel systems that
      permit the study of initial epigenetic events that potentially occur during the
      first stages of breast cancer. Non-malignant human mammary epithelial cells
      (HMECs) provide an exciting in vitro model of very early breast carcinogenesis.
      When grown in culture, HMECs are able to temporarily escape senescence and
      acquire a pre-malignant breast cancer-like phenotype (variant HMECs, or vHMECs).
      Cultured HMECs are composed mainly of cells from the basal breast epithelial
      layer. Therefore, vHMECs are considered to represent the basal-like subtype of
      breast cancer. The transition from HMECs to vHMECs in culture recapitulates the
      epigenomic phenomena that occur during the progression from normal breast to pre
      malignancy. Therefore, the HMEC model system provides the unique opportunity to
      study the very earliest epigenomic aberrations occurring during breast
      carcinogenesis and can give insight into the sequence of epigenomic events that
      lead to breast malignancy. This review provides an overview of epigenomic
      research in breast cancer and discusses in detail the utility of the HMEC model
      system to discover early epigenomic changes involved in breast carcinogenesis. 

PMID- 23168269
TI  - Cognitive behavioral therapy for shift workers with chronic insomnia.
AB  - OBJECTIVE: Shift work is a challenge in the screening and treatment of chronic
      insomnia. The aim of this study was to examine the implementation and
      effectiveness of a cognitive behavioral group intervention for insomnia (CBT-I)
      among shift workers with chronic insomnia. We also studied whether insomnia
      symptoms and intervention effects differed on work days and days off. METHODS:
      The study design was a non-randomized group intervention, including a waiting
      period prior to CBT-I as a control condition. A total of 19 media workers who
      worked irregular hours and had non-organic insomnia with features of
      psychological insomnia completed the study. We followed up with the results for a
      period of 6 months. Outcomes were assessed using a sleep diary, questionnaires,
      and actigraphy. The CBT-I groups were led by trained nurses of occupational
      health services (OHS). RESULTS: The post-intervention results showed significant
      improvements in self-reported and actigraphic sleep onset latency, and in self
      reported sleep efficiency, sleep quality, and restedness. In addition, the
      perceived severity of insomnia, sleep-related dysfunctional cognitions,
      psychiatric and somatic symptoms, and the mental component of health-related
      quality of life improved significantly. The improvements lasted and even
      strengthened over the follow-up period. The participants generally slept
      significantly better on days off than on work days, but the treatment improved
      sleep on both. CONCLUSIONS: The study showed that non-pharmacological treatment
      of insomnia can be implemented among shift workers with chronic insomnia, and
      delivery of the treatment by trained OHS nurses yields promising results. Some
      caution, however, is needed when interpreting the results because of the non
      randomized study design and small sample size.

PMID- 23168270
TI  - Diet quality of Americans differs by age, sex, race/ethnicity, income, and
      education level.
AB  - An index that assesses the multidimensional components of the diet across the
      lifecycle is useful in describing diet quality. The purpose of this study was to
      use the Healthy Eating Index-2005, a measure of diet quality in terms of
      conformance to the 2005 Dietary Guidelines for Americans, to describe the diet
      quality of Americans by varying sociodemographic characteristics in order to
      provide insight as to where diets need to improve. The Healthy Eating Index-2005
      scores were estimated using 1 day of dietary intake data provided by participants
      in the 2003-2004 National Health and Nutrition Examination Survey. Mean daily
      intakes of foods and nutrients, expressed per 1,000 kilocalories, were estimated
      using the population ratio method and compared with standards that reflect the
      2005 Dietary Guidelines for Americans. Participants included 3,286 children (2 to
      17 years), 3,690 young and middle-aged adults (18 to 64 years), and 1,296 older
      adults (65+ years). Results are reported as percentages of maximum scores and
      tested for significant differences (P <= 0.05) by age, sex, race/ethnicity,
      income, and education levels. Children and older adults had better-quality diets
      than younger and middle-aged adults; women had better-quality diets than men;
      Hispanics had better-quality diets than blacks and whites; and diet quality of
      adults, but not children, generally improved with income level, except for
      sodium. The diets of Americans, regardless of socioeconomic status, are far from
      optimal. Problematic dietary patterns were found among all sociodemographic
      groups. Major improvements in the nutritional health of the American public can
      be made by improving eating patterns.

PMID- 23168271
TI  - A technique for measuring velocity and attenuation of ultrasound in liquid foams.
AB  - We describe an experimental setup specifically designed for measuring the
      ultrasonic transmission through liquid foams, over a broad range of frequencies
      (60-600kHz). The question of determining the ultrasonic properties of the foam
      (density, phase velocity and attenuation) from the transmission measurements is
      addressed. An inversion method is proposed, tested on synthetic data, and applied
      to a liquid foam at different times during the coarsening. The ultrasonic
      velocity and attenuation are found to be very sensitive to the foam bubble sizes,
      suggesting that a spectroscopy technique could be developed for liquid foams.

PMID- 23168268
TI  - Epidemiology of infectious encephalitis, differences between a prospective study
      and hospital discharge data.
AB  - The French epidemiology of infectious encephalitis has been described in a 2007
      prospective study. We compared these results with available data (demographic
      features, causative agents, case-fatality ratio) obtained through the French
      national hospital discharge 2007 database (PMSI), in order to evaluate it as a
      surveillance tool for encephalitis. Causative agents were identified in 52% of
      cases in the study, and 38% in PMSI (P < 0.001). The incidence of encephalitis in
      France in 2007 was estimated as 2.6 cases/100 000 inhabitants. HSV and VZV were
      the most frequent aetiological agents in both databases with similar rates.
      Listeria monocytogenes and Mycobacterium tuberculosis were less frequent in PMSI
      than in the study (Listeria: 2% vs. 5%, P = 0.001; Mycobacterium: 2% vs. 8%, P <
      0.001). The case-fatality ratios were similar, except for Listeria (46% in the
      study vs. 16%). Nevertheless, despite the absence of case definitions and a
      possible misclassification weakening PMSI data, we suggest that PMSI may be used
      as a basic surveillance tool at a limited cost.

PMID- 23168272
TI  - Mutation in porcine Zip4-like zinc transporter is associated with pancreatic zinc
      concentration and apparent zinc absorption.
AB  - The aim of the present study was to analyse the sequence variability of the
      porcine Zip4-like Zn transporter gene and the association of identified sequence
      variants with average daily gain, apparent Zn absorption, plasma Zn concentration
      and Zn concentration in the liver and pancreas. For the purpose of the study, two
      different sample sets were used. Set one, which was used for sequencing and
      association analysis, included mRNA from intestinal tissue from thirty-five
      piglets of a feeding trial. Sample set two consisted of forty-six samples of
      genomic DNA from sperm or tissue of wild boars and several pig breeds and was
      used to genotype animals of different breeds. The sequence analysis of porcine
      Zip4-like complementary DNA in sample set one revealed the presence of seven
      nucleotide substitutions. Of these, six were synonymous, whereas a substitution
      of A with C in exon IX (XM_001925360 c.1430A>C) causes an amino acid exchange
      from glutamic acid to alanine (p.Glu477Ala). The association analysis revealed no
      influence of the six synonymous substitutions on Zn values, but the non
      synonymous nucleotide exchange significantly increased Zn concentration in the
      pancreas and apparent Zn absorption of the piglets in week 2 of the feeding
      trial. The parentage of the piglets and the genotyping results in sample set two
      suggest a breed-specific presence of the A allele in Pietrain for this amino acid
      substitution. These results indicate that genotype influences the Zn absorption
      abilities of individual animals, which should be taken into consideration in
      animal breeding as well as for the selection of experimental animals.

PMID- 23168273
TI  - Mitochondria in endocrinology.

PMID- 23168274
TI  - Cellular and molecular mechanisms of mitochondrial function.
AB  - Mitochondria are membrane bound organelles present in almost all eukaryotic
      cells. Responsible for orchestrating cellular energy production, they are central
      to the maintenance of life and the gatekeepers of cell death. Thought to have
      originated from symbiotic ancestors, they carry a residual genome as mtDNA
      encoding 13 proteins essential for respiratory chain function. Mitochondria
      comprise an inner and outer membrane that separate and maintain the aqueous
      regions, the intermembrane space and the matrix. Mitochondria contribute to many
      processes central to cellular function and dysfunction including calcium
      signalling, cell growth and differentiation, cell cycle control and cell death.
      Mitochondrial shape and positioning in cells is crucial and is tightly regulated
      by processes of fission and fusion, biogenesis and autophagy, ensuring a
      relatively constant mitochondrial population. Mitochondrial dysfunction is
      implicated in metabolic and age related disorders, neurodegenerative diseases and
      ischemic injury in heart and brain.

PMID- 23168276
TI  - Mitochondrial signal transduction in pancreatic beta-cells.
AB  - In the endocrine fraction of the pancreas, the task of the beta-cell is to
      continuously and perfectly adjust insulin secretion to fluctuating blood glucose
      levels, thereby maintaining glycemia and nutrient homeostasis. This glucose
      sensing coupled to insulin exocytosis depends on transduction of metabolic
      signals into intracellular messengers recognized by the exocytotic machinery.
      Central to this metabolism-secretion coupling, mitochondrial signal transduction
      refers to both integration and generation of metabolic signals, connecting
      glucose sensing to insulin exocytosis. In response to a glucose rise, nucleotides
      and metabolites are generated by mitochondria and participate, together with
      cytosolic calcium, in the stimulation of insulin release. This review describes
      the role of mitochondria in metabolic signal transduction regulating insulin
      secretion.

PMID- 23168275
TI  - Mitochondrial dynamics and morphology in beta-cells.
AB  - Mitochondrial dynamics contribute to the regulation of mitochondrial shape as
      well as various mitochondrial functions and quality control. This is of
      particular interest in the beta-cell because of the key role mitochondria play in
      the regulation of beta-cell insulin secretion function. Moreover, mitochondrial
      dysfunction has been suggested to contribute to the development of Type 2
      Diabetes. Genetic tools that shift the balance of mitochondrial fusion and
      fission result in alterations to beta-cell function and viability. Additionally,
      conditions that induce beta-cell dysfunction, such as exposure to a high nutrient
      environment, disrupt mitochondrial morphology and dynamics. While it has been
      shown that mitochondria display a fragmented morphology in islets of diabetic
      patients and animal models, the mechanism behind this is currently unknown. Here,
      we review the current literature on mitochondrial morphology and dynamics in the
      beta-cell as well as some of the unanswered question in this field.

PMID- 23168277
TI  - Uncoupling and reactive oxygen species (ROS)--a double-edged sword for beta-cell
      function? "Moderation in all things".
AB  - The ability of the mitochondrion to (a) manage fuel import to oxidize for
      adenosine tri-phosphate (ATP) generation while (b) protecting itself and the
      cellular environment from electron leak, which can generate highly reactive
      oxygen species (ROS) is a delicate balancing act. ATP is the currency of the cell
      and as such serves a signaling function as a substrate partner to many kinases
      and ion channels. While various ROS species have been viewed as a dangerous and
      toxic group of molecules, it also has a role as a signal derived from
      mitochondria, as well as other enzymatic sources: a double-edged sword. Current
      efforts to understand the biochemical mechanisms affected by ROS as a signal-
      usually noted to be hydrogen peroxide (H(2)O(2))--are exciting, but this duality
      of ROS effects also pose challenges in managing its levels to protect cells. The
      mitochondrial uncoupling protein-2 (UCP2), UCP3, and the permeability transition
      pore have been integral to efforts to try to understand what role mitochondrial
      derived ROS have in cells. In this piece we reflect on mitochondrial ROS and
      uncoupling proteins as signaling regulators. It seems that when it comes to ROS
      and uncoupling the proverb "Moderation in all things" is apt.

PMID- 23168279
TI  - Role of mitochondria in steroidogenesis.
AB  - Adrenal gonadal, placental and brain mitochondria contain several steroidogenic
      enzymes, notably the cholesterol side chain cleavage enzyme, P450scc, which is
      the enzymatic rate-limiting step in steroidogenesis which determines cellular
      steroidogenic capacity. Even before this step, the access of cholesterol to this
      enzyme system is both rate-limiting and the site of acute regulation via the
      steroidogenic acute regulatory protein (StAR) which interacts with a complex
      multi-component 'transduceosome' on the outer mitochondrial membrane (OMM). The
      components of the transduceosome include the 18 kDa translocator protein (TSPO),
      the voltage-dependent anion channel (VDAC-1), TSPO-associated protein 7 (PAP7,
      ACBD3 for acyl-CoA-binding-domain 3), and protein kinase A regulatory subunit
      1alpha (PKAR1A). The precise fashion in which these proteins interact and move
      cholesterol from the OMM to P450scc, and the means by which cholesterol is loaded
      into the OMM, remain unclear. Human deficiency diseases have been described for
      StAR and for P450scc. Mitochondria also contain several 'downstream'
      steroidogenic enzymes.

PMID- 23168280
TI  - Mitochondria and endocrine function of adipose tissue.
AB  - Excess of adipose tissue is accompanied by an increase in the risk of developing
      insulin resistance, type 2 diabetes (T2D) and other complications. Nevertheless,
      total or partial absence of fat or its accumulation in other tissues
      (lipotoxicity) is also associated to these complications. White adipose tissue
      (WAT) was traditionally considered a metabolically active storage tissue for
      lipids while brown adipose tissue (BAT) was considered as a thermogenic adipose
      tissue with higher oxidative capacity. Nowadays, WAT is also considered an
      endocrine organ that contributes to energy homeostasis. Experimental evidence
      tends to link the malfunction of adipose mitochondria with the development of
      obesity and T2D. This review discusses the importance of mitochondrial function
      in adipocyte biology and the increased evidences of mitochondria dysfunction in
      these epidemics. New strategies targeting adipocyte mitochondria from WAT and BAT
      are also discussed as therapies against obesity and its complications in the near
      future.

PMID- 23168281
TI  - Skeletal muscle mitochondrial energetics in obesity and type 2 diabetes mellitus:
      endocrine aspects.
AB  - During the development of type 2 diabetes mellitus, skeletal muscle is a major
      site of insulin resistance. The latter has been linked to mitochondrial
      dysfunction and impaired fatty acid oxidation. Some hormones like insulin,
      thyroid hormones and adipokines (e.g., leptin, adiponectin) have positive effects
      on muscle mitochondrial bioenergetics through their direct or indirect effects on
      mitochondrial biogenesis, mitochondrial protein expression, mitochondrial enzyme
      activities and/or AMPK pathway activation--all of which can improve fatty acid
      oxidation. It is therefore not surprising that treatment with these hormones has
      been proposed to improve muscle and whole body insulin sensitivity. However,
      treatment of diabetic patients with leptin and adiponectin has no effect on
      muscle mitochondrial bioenergetics showing resistance to these hormones during
      type 2 diabetes. Furthermore, treatment with most thyroid hormones has
      unexpectedly revealed negative effects on muscle insulin sensitivity. Future
      research should focus on development of agents that improve metabolic dysfunction
      downstream of hormone receptors.

PMID- 23168278
TI  - Mitochondrial sirtuins and metabolic homeostasis.
AB  - The maintenance of metabolic homeostasis requires the well-orchestrated network
      of several pathways of glucose, lipid and amino acid metabolism. Mitochondria
      integrate these pathways and serve not only as the prime site of cellular energy
      harvesting but also as the producer of many key metabolic intermediates. The
      sirtuins are a family of NAD(+)-dependent enzymes, which have a crucial role in
      the cellular adaptation to metabolic stress. The mitochondrial sirtuins SIRT3,
      SIRT4 and SIRT5 together with the nuclear SIRT1 regulate several aspects of
      mitochondrial physiology by controlling post-translational modifications of
      mitochondrial protein and transcription of mitochondrial genes. Here we discuss
      current knowledge how mitochondrial sirtuins and SIRT1 govern mitochondrial
      processes involved in different metabolic pathways.

PMID- 23168282
TI  - Real incidence of diabetes mellitus in a coronary disease population.
AB  - The high prevalence of unknown diabetes mellitus (DM) in patients with coronary
      disease and that the oral glucose tolerance test (OGTT) is the best diagnostic
      method in this context are well known. However, data about the incidence of DM in
      this population have not been well described. In the present study, we sought to
      determine the actual incidence of new-onset DM in patients with coronary disease
      using the OGTT. Our secondary objective was to validate a predictive model. We
      studied a series of 338 patients with coronary disease without known DM using the
      OGTT. After the OGTT, the patients were reclassified as normoglycemic,
      prediabetic, and unknown DM, according to the American Diabetes Association 2010
      criteria. After 3 years of follow-up, the patients without DM were again
      reassessed using the OGTT. We then built a predictive model using the
      multivariate logistic regression method and validated it using the leave-one-out
      method. The final sample was 191 patients. The mean follow-up was 3.13 years. The
      overall incidence of DM was 43.6 cases/1,000 person-years (95% confidence
      interval [CI] 26.8 to 60.4). The incidence was significantly different between
      the initially normoglycemic patients (11.5%, 95% CI 2.3% to 31.8%) and the
      prediabetic patients (70.5%, 95% CI 42.7% to 98.3%; p <0.001). A risk model that
      included the glucose level 2 hours after challenge, glycosylated hemoglobin and
      triglyceride levels, and presence of noncoronary vascular disease showed good
      predictive capacity for incident DM (area under the curve 0.882, 95% CI 0.819 to
      0.946; p <0.0001). In conclusion, the real incidence of new DM is very high in
      the coronary population, especially in those with prediabetes. It is necessary to
      use the OGTT for diagnosis, but we can optimize its indication using a risk
      model.

PMID- 23168283
TI  - Cardiovascular risk assessment of pulmonary embolism with the GRACE risk score.
AB  - Despite the existence of several risk scores, the accurate prediction of the
      prognosis in pulmonary embolism (PE) remains a challenge. The Global Registry of
      Acute Coronary Events (GRACE) risk score has a high diagnostic performance for
      adverse outcomes in acute coronary syndrome. We aimed to assess the applicability
      and extend the use of the GRACE risk score to PE. A case-control study of 206
      consecutive patients admitted with PE was performed. The GRACE, Geneva,
      Simplified Pulmonary Embolism Severity Index, Shock Index, and European Society
      of Cardiology risk scores were tested for the prediction of the primary end
      point: all-cause 30-day mortality. Comparisons between GRACE and the other risk
      scores were performed using receiver operating characteristic area under the
      curve and the integrated discrimination improvement index. All-cause 30-day
      mortality was observed in 18.9% of the patients. Unlike the other
      classifications, no adverse outcomes were observed in patients classified as low
      risk using the GRACE risk score (100% negative predictive value for GRACE risk
      score <=113). The GRACE score showed greater discriminative performance than the
      Geneva score (area under the curve 0.623, 95% confidence interval [CI] 0.53 to
      0.71), Shock Index (area under the curve 0.639, 95% CI 0.55 to 0.73), European
      Society of Cardiology (area under the curve 0.662, 95% CI 0.57 to 0.76), and
      Simplified Pulmonary Embolism Severity Index (area under the curve 0.705, 95% CI
      0.61 to 0.80), although statistical significance was not reached. The integrated
      discrimination improvement index suggested a more appropriate risk classification
      with the GRACE score. In conclusion, our results have demonstrated that the GRACE
      risk score can accurately predict 30-day mortality in patients admitted for acute
      PE. Compared to previously proposed PE prediction rules, the GRACE risk score
      presented improved overall risk classification.

PMID- 23168284
TI  - Temporal trends in medical therapies for ST- and non-ST elevation myocardial
      infarction: (from the Atherosclerosis Risk in Communities [ARIC] Surveillance
      Study).
AB  - Reports from large studies using administrative data sets and event registries
      have characterized recent temporal trends and treatment patterns for acute
      myocardial infarction. However, few were population based, and fewer examined
      differences in patterns of treatment for patients presenting with ST-segment
      elevation myocardial infarction (STEMI) and non-ST-segment elevation myocardial
      infarction (NSTEMI). The aim of this study was to examine 22-year trends in the
      use of 10 medical therapies and procedures by STEMI and NSTEMI classification in
      30,986 definite or probable myocardial infarctions in the Atherosclerosis Risk in
      Communities (ARIC) Community Surveillance Study from 1987 to 2008. Weighted
      multivariate Poisson regression, controlling for gender, race and center
      classification, age, and Predicting Risk of Death in Cardiac Disease Tool score,
      was used to estimate average annual percentage changes in medical therapy use.
      From 1987 to 2008, 6,106 hospitalized events (19.7%) were classified as STEMIs
      and 20,302 (65.5%) as NSTEMIs. Among patients with STEMIs, increases were noted
      in the use of angiotensin-converting enzyme inhibitors (6.4%, 95% confidence
      interval [CI] 5.7 to 7.2), antiplatelet agents other than aspirin (5.0%, 95% CI
      4.0% to 6.0%), lipid-lowering medications (4.5%, 95% CI 3.1% to 5.8%), beta
      blockers (2.7%, 95% CI 2.4% to 3.0%), aspirin (1.2%, 95% CI 1.0% to 1.3%), and
      heparin (0.8%, 95% CI 0.4% to 1.3%). Among patients with NSTEMIs, the use of
      angiotensin-converting enzyme inhibitors (5.5%, 95% CI 5.0% to 6.1%),
      antiplatelet agents other than aspirin (3.7%, 95% CI 2.7% to 4.7%), lipid
      lowering medications (3.0%, 95% CI% 1.9 to 4.1%), beta blockers (4.2%, 95% CI
      3.9% to 4.4%), aspirin (1.9%, 95% CI 1.6% to 2.1%), and heparin (1.7%, 95% CI
      1.3% to 2.1%) increased. Among patients with STEMIs, decreases in the use of
      thrombolytic agents (-7.2%, 95% CI -7.9% to -6.6%) and coronary artery bypass
      grafting (-2.4%, 95% CI -3.6% to -1.2%) were observed. Similar increases in
      percutaneous coronary intervention and decreases in the use of thrombolytic
      agents and coronary artery bypass grafting were noted among all patients. In
      conclusion, trends of increasing use of evidence-based therapies were found for
      patients with STEMIs and those with NSTEMIs over the past 22 years.

PMID- 23168285
TI  - Effects of niacin on glucose levels, coronary stenosis progression, and clinical
      events in subjects with normal baseline glucose levels (<100 mg/dl): a combined
      analysis of the Familial Atherosclerosis Treatment Study (FATS), HDL
      Atherosclerosis Treatment Study (HATS), Armed Forces Regression Study (AFREGS),
      and Carotid Plaque Composition by MRI during lipid-lowering (CPC) study.
AB  - Although the effect of niacin on the glucose levels in subjects with diabetes
      mellitus has been investigated, niacin's effects on the glucose levels and
      atherosclerosis in subjects with normal glucose levels have not been well
      established. We examined the effect of niacin on the glucose levels, coronary
      stenosis progression using quantitative coronary angiography, and clinical events
      in 407 subjects who had a baseline glucose level <100 mg/dl and were enrolled in
      the Familial Atherosclerosis Treatment Study (FATS), HDL-Atherosclerosis
      Treatment Study (HATS), Armed Forces Regression Study (AFREGS), or Carotid Plaque
      Composition by MRI during lipid-lowering (CPC) study testing active niacin
      therapy. Although the fasting glucose levels increased significantly within 3
      years in both subjects treated with niacin (from 85.6 +/- 9.5 to 95.5 +/- 19.7
      mg/dl, p <0.001) and without niacin (from 85.2 +/- 9.6 to 90 +/- 17.9 mg/dl, p =
      0.009), those treated with niacin had a significantly larger increase in glucose
      levels than those not taking niacin (9.88 vs 4.05 mg/dl, p = 0.002). Overall, 29%
      of subjects developed impaired fasting glucose within 3 years. Incident impaired
      fasting glucose was significantly more likely to be observed in subjects treated
      with niacin than in those who were not. However, the frequency of new-onset
      diabetes mellitus did not differ significantly between the 2 groups (5.6% vs
      4.8%, p = 0.5). Niacin-treated subjects compared to untreated subjects had
      significantly less change in mean coronary stenosis (0.1 +/- 0.3% vs 2 +/- 12%, p
      <0.0001) and less major cardiovascular events (8% vs 21%, p = 0.001). In
      conclusion, the use of niacin for 3 years in subjects with normal baseline
      glucose levels was associated with an increase in blood glucose levels and the
      risk of developing impaired fasting glucose, but not diabetes mellitus, and was
      associated with a significantly reduced incidence of coronary stenosis
      progression and major cardiovascular events.

PMID- 23168286
TI  - Relation of vitamin D and parathyroid hormone to cardiac biomarkers and to left
      ventricular mass (from the Cardiovascular Health Study).
AB  - Vitamin D and parathyroid hormone (PTH) may affect cardiovascular health in
      patients with kidney disease and in the general population. The aim of this study
      was to investigate associations of serum 25-hydroxyvitamin D (25(OH)D) and PTH
      concentrations with a comprehensive set of biochemical, electrocardiographic, and
      echocardiographic measurements of cardiac structure and function in the
      Cardiovascular Health Study. A total of 2,312 subjects who were free of
      cardiovascular disease at baseline were studied. Serum 25(OH)D and intact PTH
      concentrations were measured using mass spectrometry and a 2-site immunoassay.
      Outcomes were N-terminal pro-B-type natriuretic peptide, cardiac troponin T,
      electrocardiographic measures of conduction, and echocardiographic measures of
      left ventricular mass and diastolic dysfunction. At baseline, subjects had a mean
      age of 73.9 +/- 4.9 years, 69.7% were women, and 21% had chronic kidney disease
      (glomerular filtration rate <60 ml/min). Mean 25(OH)D was 25.2 +/- 10.2 ng/ml,
      and median PTH was 51 pg/ml (range 39 to 65). After adjustment, 25(OH)D was not
      associated with any of the biochemical, conduction, or echocardiographic
      outcomes. Serum PTH levels >=65 pg/ml were associated with greater N-terminal pro
      B-type natriuretic peptide, cardiac troponin T, and left ventricular mass in
      patients with chronic kidney disease. The regression coefficients were: 120 pg/ml
      (95% confidence interval 36.1 to 204), 5.2 pg/ml (95% confidence interval 3.0 to
      7.4), and 17 g (95% confidence interval 6.2 to 27.8) (p <0.001). In subjects with
      normal kidney function, PTH was not associated with the outcomes. In conclusion,
      in older adults with chronic kidney disease, PTH excess is associated with higher
      N-terminal pro-B-type natriuretic peptide, cardiac troponin T, and left
      ventricular mass. These findings suggest a role for PTH in cardiovascular health
      and the prevention of cardiac diseases.

PMID- 23168287
TI  - Indexes of von Willebrand factor as biomarkers of aortic stenosis severity (from
      the Biomarkers of Aortic Stenosis Severity [BASS] study).
AB  - We correlated von Willebrand factor (VWF) activity indexes and brain natriuretic
      peptide (BNP) with measures of aortic stenosis (AS) severity, bleeding, symptoms,
      and freedom from death or aortic valve replacement. Patients with AS (n = 66 [16
      mild, 20 moderate, and 30 severe]) and aortic valve replacement (n = 21) were
      assessed with VWF antigen, VWF latex agglutination immunoturbidic activity,
      platelet function analyzer collagen plus adenosine diphosphate (PFA-CADP), VWF
      multimer ratio, and BNP level after echocardiography. In patients with AS, the
      mean gradient correlated with BNP (Spearman r = 0.29, p = 0.02), VWF latex
      agglutination immunoturbidic activity/VWF antigen ratio (r = -0.41, p <0.001),
      PFA-CADP (r = 0.49, p <0.001), and VWF multimer ratio (r = -0.76, p <0.001). The
      area under the curve for detection of severe AS was 0.62 (95% confidence interval
      [CI] 0.48 to 0.77) by elevated BNP, 0.81 (95% CI 0.69 to 0.92) by PFA-CADP
      closure time, 0.69 (95% CI 0.55 to 0.82) by VWF latex agglutination
      immunoturbidic activity/VWF antigen ratio, and 0.86 (95% CI 0.76 to 0.95) by VWF
      multimer ratio. For the VWF multimer ratio, a threshold of 0.15 yielded a
      sensitivity and specificity for severe AS of 77% and positive predictive value of
      74%. Bleeding (in 14%) was associated with a prolonged PFA-CADP time and reduced
      VWF latex agglutination immunoturbidic activity/VWF antigen ratio. Symptoms were
      associated with elevated BNP and low Duke Activity Status Index score. In 66
      patients with AS, freedom from death (n = 4) or aortic valve replacement (n = 22)
      was associated with PFA-CADP (p = 0.003), VWF high-molecular-weight multimers (p
      = 0.009), and VWF latex agglutination immunoturbidic activity/VWF antigen ratio
      (p <0.001) but not BNP (p = 0.32). In severe AS versus aortic valve replacement,
      the PFA-CADP and VWF multimer ratio differed (p <0.001), but BNP and the VWF
      latex agglutination immunoturbidic activity/VWF antigen ratio did not. In
      conclusion, the VWF activity indexes were associated with AS severity and
      bleeding and were predictive of cardiovascular outcomes.

PMID- 23168288
TI  - Desmin mutations and arrhythmogenic right ventricular cardiomyopathy.
AB  - Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited heart
      muscle disease characterized by fibrofatty replacement of the myocardium and
      ventricular arrhythmias, associated with mutations in the desmosomal genes. Only
      a missense mutation in the DES gene coding for desmin, the intermediate filament
      protein expressed by cardiac and skeletal muscle cells, has been recently
      associated with ARVC. We screened 91 ARVC index cases (53 negative for mutations
      in desmosomal genes and an additional 38 carrying desmosomal gene mutations) for
      DES mutations. Two rare missense variants were identified. The heterozygous
      p.K241E substitution was detected in 1 patient affected with a severe form of
      ARVC who also carried the p.T816RfsX10 mutation in plakophilin-2 gene. This DES
      substitution, showing an allele frequency of <0.01 in the control population, is
      predicted to cause an intolerant amino acid change in a highly conserved protein
      domain. Thus, it can be considered a rare variant with a possible modifier effect
      on the phenotypic expression of the concomitant mutation. The previously known
      p.A213V substitution was identified in 1 patient with ARVC who was negative for
      mutations in the desmosomal genes. Because a greater prevalence of p.A213V has
      been reported in patients with heart dilation than in control subjects, the
      hypothesis that this rare variant could have an unfavorable effect on cardiac
      remodeling cannot be ruled out. In conclusion, our data help to establish that,
      in the absence of skeletal muscle involvement suggestive of a desminopathy, the
      probability of DES mutations in ARVC is very low. These findings have important
      implications in the mutation screening strategy for patients with ARVC.

PMID- 23168289
TI  - Refining the role of antiplatelet therapy in medically managed patients with
      acute coronary syndrome.
AB  - Dual-antiplatelet therapy with aspirin plus a P2Y(12) receptor inhibitor is
      recommended for use as first-line therapy in patients with acute coronary
      syndromes (ACS) who undergo high-risk percutaneous coronary intervention.
      However, revascularization may not be a beneficial option for some subgroups of
      patients with ACS. This includes a broad spectrum of lower risk patients as well
      as high-risk patients with numerous previous revascularizations and those who are
      at high risk for complications, such as those with complex coronary anatomy and
      co-morbidities such as diabetes mellitus, chronic kidney disease, or advanced age
      and frailty. For such patients, there remains an unmet need for evaluation of
      alternatives to the currently recommended treatment options. Notably, there is a
      paucity of prospective data regarding management approaches to medically managed
      patients with ACS. Thus, this group of medically managed patients with ACS would
      benefit from inclusion in clinical trials investigating therapeutic options for
      patients not scheduled to undergo invasive procedures, such as those who are
      targeted for pharmacologic management only. In conclusion, in this review, the
      investigators revisit data from clinical studies of dual-antiplatelet therapy in
      ACS to highlight areas of unmet need in antiplatelet therapy in patients with ACS
      and to examine the use of newer agents in subgroups, such as medically managed
      patients with ACS, that would potentially benefit from more potent platelet
      inhibition after ACS.

PMID- 23168290
TI  - Relation of morbid obesity and female gender to risk of procedural complications
      in patients undergoing atrial fibrillation ablation.
AB  - Obese patients with atrial fibrillation (AF) are frequently treated with AF
      ablation. We sought to examine whether a body mass index (BMI) threshold exists
      beyond which the odds of experiencing a complication from AF ablation increases.
      All patients enrolled in the Vanderbilt AF Registry who underwent catheter-based
      AF ablation from May 1999 to February 2012 were included. Major complications
      were recorded. Morbid obesity was defined as a BMI >40 kg/m(2) and examined in
      multivariable analysis. A total of 35 complications (6.8%) occurred in 512
      ablations. Morbidly obese patients experienced a greater rate of complications (6
      of 42, 14.3%) than the nonmorbidly obese (29 of 470, 6.2%; p = 0.046). Using a
      discrete BMI cutoff, the odds of complications increased 3.1-fold in those with
      morbid obesity (odds ratio [OR] 3.1, 95% confidence interval [CI] 1.1 to 8.4, p =
      0.03) and 2.1-fold for female gender (OR 2.1, 95% CI 1.04 to 4.38, p = 0.04).
      With BMI as a continuous variable, the odds of complications increased by 5% per
      1 unit increase in BMI (OR 1.05, 95% CI 1.0 to 1.11, p = 0.05), and the increase
      for female gender was 2.2-fold (OR 2.2, 95% CI 1.1 to 4.6, p = 0.03). In
      conclusion, morbid obesity represents a BMI threshold above which the odds of
      complications with AF ablation increase significantly. The increase in
      complications appears to be driven primarily by events in women, suggesting that
      morbidly obese women are a special population when considering AF ablation.

PMID- 23168291
TI  - Comparison of surgical septal myectomy to medical therapy alone in patients with
      hypertrophic cardiomyopathy and syncope.
AB  - The presence of syncope despite medical therapy in patients with hypertrophic
      cardiomyopathy (HC) is considered an indication for surgical myectomy; however,
      no study has examined the long-term effects on recurrent syncope and survival
      after surgery in these patients. We examined 239 patients with HC and a history
      of syncope who had undergone surgical myectomy (mean age 48 +/- 17 years; 56%
      men). The patients were age- and gender-matched to patients with HC and syncope
      who were treated medically without myectomy (mean age 51 +/- 16 years; 59% men).
      The median follow-up period was 4.7 years (0.8, 11.3). The recurrence rate of
      syncope was 11% in the myectomy patients and 40% in the medical group (p
      <0.0001). Multiple episodes of syncope, left ventricular outflow tract
      obstruction, and recent syncope were identified as baseline predictors of
      recurrent syncope. Survival free of all-cause mortality was greater for patients
      who had undergone surgical myectomy than for the medically treated patients (10
      year estimate 82 +/- 4% vs 69 +/- 4%; p = 0.01). In conclusion, surgical myectomy
      in patients with HC and a history of syncope was associated with a reduction in
      recurrent syncope and increased survival.

PMID- 23168293
TI  - Bone hemodynamic responses to changes in external pressure.
AB  - Adequate blood supply and circulation to the bones is required to maintain a
      healthy skeleton. Inadequate blood perfusion is associated with numerous bone
      pathologies and a decrease in bone mineral density, yet bone hemodynamics remains
      poorly understood. This study aims to 1) quantify bone hemodynamic responses to
      changes in external pressure, and 2) identify the predominant mechanisms
      regulating bone hemodynamic responses to pressure changes. Photoplethysmography
      was used to measure bone and skin perfusion in response to changes in external
      pressure. Single-limb pressure chamber experiments were performed over a pressure
      range of -50 to +50mmHg. Bone perfusion is decreased at all negative pressures,
      and larger decrements in perfusion are observed at the more extreme pressure
      differences. At positive pressures we observed an initial increase in perfusion
      followed by activation of intramuscular pressure receptors at +30mmHg, which
      overrides the initial response and results in decreased perfusion at the highest
      positive pressure levels. The myogenic effect is observed and is shown to be the
      predominant control mechanism in bone over a wide range of pressure exposures.
      Greater understanding of these hemodynamic mechanisms may be important in
      developing new drugs and therapies to treat various bone disorders.

PMID- 23168292
TI  - The molecular mechanisms underlying the pharmacological actions of estrogens,
      SERMs and oxysterols: implications for the treatment and prevention of
      osteoporosis.
AB  - Estrogen therapy and hormone therapy are effective options for the prevention and
      treatment of osteoporosis, although because of their significant side effect
      profile, long term use for these applications is not recommended. Whereas SERMs
      (Selective Estrogen Receptor Modulators) exhibit a more favorable side effect
      profile, the currently available medicines in this class are substantially less
      effective in bone than classical estrogens. However, the results of substantial
      efforts that have gone into defining the mechanisms that underlie the
      pharmacology of estrogens, antiestrogens and SERMs have informed the development
      of the next generation of SERMs and have led to the development of TSECs (Tissue
      Selective Estrogen Complexes), a new class of ER-modulator. Further, the recent
      determination that the oxysterol 27-hydroxycholesterol functions as an endogenous
      SERM has highlighted an unexpected link between hypercholesterolemia and bone
      biology and must be considered in any discussions of ER-pharmacology. This review
      considers the most recent progress in our understanding of ER pharmacology and
      how this has and will be translated into new medicines for the treatment and
      prevention of osteoporosis.

PMID- 23168294
TI  - 25-Hydroxyvitamin D insufficiency is associated with cardiometabolic risk in
      Korean adolescents: the 2008-2009 Korea National Health and Nutrition Examination
      Survey (KNHANES).
AB  - OBJECTIVE: Vitamin D insufficiency is known to be related to cardiometabolic
      disorders; however, the associations among serum 25-hydroxyvitamin D (25(OH)D)
      concentration and metabolic syndrome and cardiometabolic risk factors in children
      and adolescents have not yet been clearly delineated. For this reason, we
      investigated the relationship among serum 25(OH)D concentration and metabolic
      syndrome and cardiometabolic risk factors among Korean adolescents. DESIGN: We
      performed a cross-sectional analysis and used hierarchical multivariate logistic
      regression analysis models to adjust for confounding variables. SETTING: We used
      the data gathered during the 2008-2009 Korea National Health and Nutrition
      Examination Survey (KNHANES). SUBJECTS: Our subjects included 1504 Korean
      adolescents aged 12-18 years who participated in the KNHANES. RESULTS: Vitamin D
      insufficiency, defined as 25(OH)D concentration <50 nmol/l, was found in 75.3% of
      Korean adolescents and was associated with an increased risk of the prevalence of
      metabolic syndrome. Waist circumference and BMI were the most closely correlated
      cardiometabolic components of metabolic syndrome according to serum 25(OH)D
      status, but no significant relationship was found between serum 25(OH)D
      concentration and insulin resistance or for the risks for high blood pressure,
      hyperglycaemia, reduced HDL-cholesterol or hypertriacylglycerolaemia, with or
      without adjustment for confounding variables. CONCLUSIONS: Low serum 25(OH)D
      concentration appears to be associated with several cardiometabolic risk factors
      and an increased risk of the prevalence of metabolic syndrome in Korean
      adolescents.

PMID- 23168295
TI  - Importance of dose selection in novel oral anticoagulants for atrial
      fibrillation.
AB  - There are several excellent alternatives to warfarin on the horizon for atrial
      fibrillation. Results from the trials, as well as pharmacokinetic data from the
      edoxaban studies, suggest that dose selection, based on pharmacokinetic and
      pharmacodynamic properties, is a critical component in the development of novel
      anticoagulants. Greater flexibility in dosing with edoxaban and the opportunity
      for dose adjustment throughout the ENGAGE AF-TIMI 48 trial may be advantageous in
      the competitive field of novel oral anticoagulants.

PMID- 23168296
TI  - Evolutionary hypothesis of the Mevalonate Kinase Deficiency.
AB  - Mevalonate Kinase Deficiency (MKD) is an autosomal-recessively inherited disorder
      of cholesterol biosynthesis with higher prevalence in the Netherlands and other
      North European countries. MKD is due to mutations in the second enzyme of
      mevalonate pathway (mevalonate kinase, MK/MVK) which results in reduced enzymatic
      activity and in the consequent shortage of downstream compounds. In most severe
      cases the deregulation of mevalonate pathway is associated with a decrease in
      serum cholesterol. More than 100 pathological mutations have been described in
      the MVK gene so far, and a founder effect has been hypothesized as responsible
      for the diffusion of the most frequent disease-associated mutations. In the acute
      phase of disease, patients affected with MKD present low cholesterol levels
      comparable to their basal physiologic conditions, already characterized by lower
      cholesterol levels when compared to healthy individuals. Low cholesterol levels
      are widely known to correlate with the reduction of cardiovascular events. We
      hypothesize a selective advantage for heterozygote carriers of the most frequent
      MVK mutations in those countries where the diet is characterized by high
      consumption of saturated animal fats rich in cholesterol. This could explain the
      maintenance in North European population of the main mutations leading to MKD and
      the distribution world-wide of these mutations that followed the migrations of
      North European populations.

PMID- 23168297
TI  - A mouse mammary epithelial cell line permissive for highly efficient human
      adenovirus growth.
AB  - Although a few immunocompetent animal models to study the immune response against
      human adenoviruses (HAdV) are available, such as Syrian hamsters and cotton rats,
      HAdV replication is several logs lower compared to human control cells. We have
      identified a non-transformed mouse epithelial cell line (NMuMG) where HAdV-2 gene
      expression and progeny formation was as efficient as in the highly permissive
      human A549 cells. HAdV from species, D and E (HAdV-37 and HAdV-4, respectively)
      also caused a rapid cytopathic effect in NMuMG cells, while HAdV from species A,
      B1, B2 and F (HAdV-12, HAdV-3, HAdV-11 and HAdV-41, respectively) failed to do
      so. NMuMG cells might therefore be useful in virotherapy research and the
      analysis of antiviral defense mechanisms and the determination of toxicity,
      biodistribution and specific antitumour activity of oncolytic HAdV vectors.

PMID- 23168298
TI  - Long-term vitamin D3 supplementation is more effective than vitamin D2 in
      maintaining serum 25-hydroxyvitamin D status over the winter months.
AB  - Public health recommendations do not distinguish between vitamin D2 and vitamin
      D3, yet disagreement exists on whether these two forms should be considered
      equivalent. The objective of the present study was to evaluate the effect of a
      daily physiological dose of vitamin D2 or vitamin D3 on 25-hydroxyvitamin D
      (25(OH)D) status over the winter months in healthy adults living in Dunedin, New
      Zealand (latitude 46 degrees S). Participants aged 18-50 years were randomly
      assigned to 25 MUg (1000 IU) vitamin D3 (n 32), 25 MUg (1000 IU) vitamin D2 (n
      31) or placebo (n 32) daily for 25 weeks beginning at the end of summer. A per
      protocol approach, which included >= 90 % supplement compliance, was used for all
      analyses. Serum 25-hydroxyvitamin D3 (25(OH)D3), 25-hydroxyvitamin D2 (25(OH)D2)
      and parathyroid hormone (PTH) were measured at baseline and at 4, 8, 13 and 25
      weeks. Geometric mean total serum 25(OH)D concentrations (sum of 25(OH)D2 and
      25(OH)D3) at baseline was 80 nmol/l. After 25 weeks, participants randomised to
      D2 and placebo had a significant reduction in serum 25(OH)D3 concentrations over
      the winter months compared with vitamin D3-supplemented participants (both P<
      0.001). Supplementation with vitamin D2 increased serum 25(OH)D2 but produced a 9
      (95 % CI 1, 17) nmol/l greater decline in the 25(OH)D3 metabolite compared with
      placebo (P< 0.036). Overall, total serum 25(OH)D concentrations were 21 (95 % CI
      14, 30) nmol/l lower in participants receiving vitamin D2 compared with those
      receiving D3 (P< 0.001), among whom total serum 25(OH)D concentrations remained
      unchanged. No intervention-related changes in PTH were observed. Daily
      supplementation of vitamin D3 was more effective than D2; however, the functional
      consequence of the differing metabolic response warrants further investigation.

PMID- 23168299
TI  - Training neonatal staff for the future in neonatal palliative care.
AB  - Neonatal palliative care is an emerging specialty, developing in the context of
      the significant prevalence of life-limiting and life-threatening conditions
      amongst the population treated and cared for by neonatologists and neonatal
      nurses. In this paper we explore the need and provision for training among
      practitioners in neonatal palliative care to date. We describe several different
      educational and training programme models with attention to structure, content
      and impact on participants' knowledge, capacity, competency and confidence in
      delivering palliative care services suggesting what is needed to ensure the
      highest standards of care for newborns and babies with life-limiting illness and
      life-threatening conditions.

PMID- 23168301
TI  - The antileukemic activity of modified fibrinogen-methotrexate conjugate.
AB  - BACKGROUND: The search for new, innovative methods to treat all types of
      diseases, especially cancer-related ones, is a challenge taken by pharmaceutical
      companies and academic institutions. The use of conjugates containing widely
      known and widely-used bioactive substances is one of the ways to solve this
      problem. Research into drug binding with macromolecular carrier systems has
      joined the search for new therapeutic strategies. METHODS: The main goal of this
      paper is the potential offered by the use of fibrinogen derivatives as an
      antileukemic drug carrier. Physicochemical properties of the obtained conjugate
      were analyzed, characterizing alterations in relation to the starting carrier and
      analyzing biological implications. The intraperitoneally (i.p.) inoculated P388
      mouse leukemia model for in vivo studies was used. RESULTS AND CONCLUSIONS:
      Conjugates consisting of a fibrinogen derivative with a covalently bound
      anticancer drug were developed. Carrier preparation and a conjugate synthesis in
      aqueous solution were formulated, as well as purification of the conjugate was
      performed. The study showed that the survival of leukemia mice treated with FH
      MTX conjugate was indeed significantly longer than survival in both untreated
      animals (control) and mice treated with unbound MTX. A significant increase in
      the antileukemic activity of MTX conjugated with hydrolysed fibrinogen was
      observed as compared with the unconjugated drug. Reported data suggest that
      hydrolysed fibrinogen can serve as a carrier molecule for the MTX drug with the
      aim of enhancing its antileukemic activity. GENERAL SIGNIFICANCE: Conjugates
      consisting of a fibrinogen derivative with a covalently bound anticancer drug
      seem to be a promising anticancer drug.

PMID- 23168302
TI  - Ethical perspectives on knowledge translation in rehabilitation.
AB  - Although the literature on the ethical dimensions of knowledge creation, use, and
      dissemination is voluminous, it has not particularly examined the ethical
      dimensions of knowledge translation in rehabilitation. Yet, whether research is
      done in a wet lab or treatments are provided to patients in therapeutic settings,
      rehabilitation professionals commonly use (as well as create) knowledge and
      disseminate it to peers, patients, and various others. This article will refer to
      knowledge creation, use, and transfer as knowledge translation and examine some
      of its numerous ethical challenges. Three ethical dimensions of knowledge
      translation will particularly attract our attention: (1) the quality of knowledge
      disseminated to rehabilitationists; (2) ethical challenges in being too easily
      persuaded by or unreasonably resistant to putative knowledge; and (3)
      organizational barriers to knowledge translation. We will conclude with some
      recommendations on facilitating the ethical soundness of knowledge translation in
      rehabilitation.

PMID- 23168303
TI  - The effect of in-hospital developmental care on neonatal morbidity, growth and
      development of preterm Taiwanese infants: a randomized controlled trial.
AB  - INTRODUCTION: Intervention studies of developmental care for preterm infants in
      Western societies have shown early but unsustainable effects on child outcomes,
      however only a limited of studies have examined if developmental care
      interventions produce similar effects in Eastern cultural contexts. AIMS: To
      examine the effectiveness of in-hospital developmental care on neonatal
      morbidity, growth and development of preterm infants with very low birth weight
      (VLBW; birth weight<1500 g) in Taiwan. METHODS: One hundred and seventy-eight
      VLBW preterm infants were randomly assigned to the clinical trial during
      hospitalization at three hospitals in Taiwan; the control group received five
      sessions of standard child-focused developmental care and the intervention group
      received five sessions of child- and parent-focused developmental care. Sixty-two
      normal term infants were also included as a comparison group. Infants were
      examined for morbidity, growth and developmental outcomes at term age. RESULTS:
      At study entry, more infants in the intervention group were twins or multiples
      than those in the control group (29% vs. 16%, p=0.05). After adjusting for birth
      set, the intervention group had lower incidences of stage II-III retinopathy
      (odds ratio [OR]=0.34 [95% confidence interval (CI): 0.15-0.79]; p=0.01) and
      feeding desaturation (OR=0.32 [95% CI: 0.10-1.00]; p=0.05) and had greater daily
      weight gains (difference=2.0 g/day [95% CI: 0-4.0 g/day]; p=0.05) as compared
      with the control group. However, the intervention and control groups did not
      differ in any of the neurodevelopmental measures. CONCLUSIONS: In-hospital
      developmental care has short-term benefits for Taiwanese VLBW preterm infants in
      reducing the risk of retinopathy and feeding desaturation as well as in enhancing
      weight gains at term age.

PMID- 23168304
TI  - Prevalence of sexually transmitted infections among HIV-infected women in Brazil.
AB  - This study aimed to evaluate the prevalence of sexually transmitted infections
      (STIs) and associated risk factors in HIV-infected pregnant women followed for
      prenatal care in Salvador, Bahia. This was a cross-sectional study of 63 women
      seeking prenatal care at a reference center. Participants were interviewed
      regarding socio-epidemiological and clinical history, and were tested for HBsAg,
      anti-HCV, anti HTLV I/II, VDRL, Chlamydia trachomatis, Neisseria gonorrhoeae,
      Mycoplasma hominis, Ureaplasma urealyticum, CD4 count, and HIV plasma viral load.
      The main outcome variable was the presence of any STI. The mean age of patients
      was 28.2 years (16-40 years). 23 (36.5%) were diagnosed with at least one STI.
      The frequency of diagnoses was: HBV, 3.2%; HCV, 8.1%; HTLV I/II, 3.4%; syphilis,
      9.5%; Chlamydia trachomatis, 11.1%; HPV, 15.0%; Mycoplasma hominis, 2.1%, and
      Ureaplasma urealyticum, 2.1%. No case of Neisseria gonorrhoeae was identified. No
      association was found between socio-epidemiological variables and the presence of
      an STI. CD4 T lymphocyte < 500 cells/MUL (p=0.047) and plasma viral load >1,000
      copies (p = 0.027) were associated with the presence of STI. STIs are frequent in
      pregnant women infected with HIV, and all HIV-infected pregnant women should be
      screened to decrease transmission of these pathogens and to protect their own
      health.

PMID- 23168306
TI  - Why we should CARE about polypectomy technique.

PMID- 23168305
TI  - Prevalence of hepatitis B among pregnant women assisted at the public maternity
      hospitals of Sao Luis, Maranhao, Brazil.
AB  - INTRODUCTION: Hepatitis B virus (HBV) infection is an important worldwide public
      health problem. In Brazil, the Ministry of Health estimates that 15% of the
      population has had contact with HBV, and that the mean rate of chronic carriers
      in Northeastern Brazil is around 0.5%. OBJECTIVE: The aim of this study was to
      assess the prevalence of HBV markers in pregnant women receiving prenatal care at
      the public maternity hospitals of Sao Luis. METHODS: Demographical and
      epidemiological data were collected from 541 pregnant women according to the
      research protocol. Blood samples were collected, and the anti-HBc test was
      performed first. If positive, the sample was subsequently tested for HBsAg and
      anti-HBs. All HBsAg and/or anti-HBc positive samples were additionally tested for
      HBV-DNA. RESULTS: 40 (7.4%) pregnant women turned out positive for anti-HBc. Of
      those, five (0.9%) were HBsAg positive, four (0.7%) were anti-HBc positive with
      negative HBsAg and anti-HBs, and 31 (5.7%) were positive for anti-HBc and anti
      HBs. Anti-HBc positivity was associated with family history of hepatitis and
      education level below 11 years of schooling. HBV-DNA was positive in only one
      HBsAg-positive sample. There was no HBV-DNA positivity among HBsAg negative
      samples. CONCLUSIONS: The prevalence of HBsAg in pregnant women in this study
      confirmed that Sao Luis is a low endemicity area. Occult hepatitis B was not
      detected in these samples.

PMID- 23168307
TI  - Using rewards-based incentives to increase purchase of fruit and vegetables in
      lower-income households: design and start-up of a randomized trial.
AB  - OBJECTIVE: To report the design and baseline results of a rewards-based incentive
      to promote purchase of fruit and vegetables by lower-income households. DESIGN: A
      four-phase randomized trial with wait-listed controls. In a pilot study, despite
      inadequate study coupon use, purchases of fresh fruit (but not vegetables)
      increased, but with little maintenance. In the present study, credits on the
      study store gift card replace paper coupons and a tapering phase is added. The
      primary outcome is the number of servings of fresh and frozen fruit and
      vegetables purchased per week. SETTING: A large full-service supermarket located
      in a predominantly minority community in Philadelphia, Pennsylvania, USA.
      SUBJECTS: Fifty-eight households, with at least one child living in the home.
      RESULTS: During the baseline period, households purchased an average of 3.7
      servings of fresh vegetables and an average of less than 1 serving of frozen
      vegetables per week. Households purchased an average of 1.9 servings of fresh
      fruit per week, with little to no frozen fruit purchases. Overall, the range of
      fresh and frozen produce purchased during this pre-intervention period was
      limited. CONCLUSIONS: At baseline, produce purchases were small and of limited
      variety. The study will contribute to understanding the impact of financial
      incentives on increasing the purchases of healthier foods by lower-income
      populations.

PMID- 23168308
TI  - Rhenium(I) tricarbonyl complexes of salicylaldehyde semicarbazones: synthesis,
      crystal structures and cytotoxicity.
AB  - A series of N,N-disubstituted salicylaldehyde semicarbazones (SSCs),
      HOC(6)H(4)CHN-NHCONR(2), and their rhenium(I) tricarbonyl complexes,
      [ReBr(CO)(3)(SSC)], have been synthesised and characterised by IR and (1)H NMR
      spectroscopy. Crystallographic analysis of the complex [ReBr(CO)(3)(H(2)Bu(2))]
      (H(2)Bu(2)=SSC where R=Bu(n)) showed that the SSC acts as a bidentate ligand via
      its imino nitrogen and carbonyl oxygen atoms. The [ReBr(CO)(3)(SSC)] complexes
      exhibit moderate to high cytotoxicities towards MOLT-4 cells (IC(50)=1-24MUM, cf.
      18MUM for cisplatin), and the majority of them are virtually non-toxic against
      non-cancerous human fibroblasts. Apoptotic assays of [ReBr(CO)(3)(H(2)Bnz(2))]
      (Bnz=benzyl) revealed that it mediates cytotoxicity in MOLT-4 cells via
      apoptosis. The complex [ReBr(CO)(3)(H(2)Bnz(2))] reacts with guanosine by proton
      transfer from the phenolic OH group to N(7) of guanosine. In (CD(3))(2)SO,
      [ReBr(CO)(3)(H(2)Bnz(2))] undergoes facile conversion to the dimeric complex,
      [Re(CO)(3)(HBnz(2))](2), via bromide dissociation.

PMID- 23168309
TI  - Investigating the appropriate mode of expressing lysine requirement of fish
      through non-linear mixed model analysis and multilevel analysis.
AB  - Accurate estimates of lysine requirement are essential to fish feed formulation.
      However, controversy exists regarding the most appropriate mode to express lysine
      requirement. In the fish nutrition literature, essential amino acid (AA)
      requirement has been expressed as a percentage of diet, a percentage of dietary
      crude protein or a ratio to dietary digestible energy (DE). The controversy lies
      in the different assumptions regarding the effects of dietary protein and DE on
      lysine requirement. Non-linear mixed model analysis and multilevel analysis were
      carried out to investigate whether dietary protein or DE affected lysine
      requirement of fish. The non-linear mixed model analysis suggests that expressing
      lysine requirement as a percentage of dietary protein provides a better goodness
      of fit to the modelling dataset than expressing requirement as a fixed
      concentration of diet, which in turn is generally better than expressing
      requirement as a ratio to DE. Results from the multilevel analysis confirm that
      dietary protein content has a significant effect on lysine requirement, while DE
      does not. The findings of the present study could contribute to a better
      understanding of the underlying dietary factors that affect AA requirements of
      fish. The results of the present study could also be useful for developing
      nutritional guidelines and feed formulations for fish.

PMID- 23168310
TI  - A new pentaplex-nested PCR to detect five pathogenic bacteria in free living
      amoebae.
AB  - Changes in water use and anthropogenic activity have major impacts on the quality
      of natural aquatic ecosystems, water distribution and wastewater plants. One of
      the main problems is the presence of some pathogenic microorganisms that are
      resistant to disinfection procedures when they are hosted by free living amoeba
      and that in many cases are hardly detectable by culture-based procedures. In this
      work we report a sensitive, low-cost procedure consisting of a pentaplex-nested
      PCR that allows simultaneous detection of Legionella pneumophila, Mycobacterium
      spp., Pseudomonas spp., Vibrio cholerae and the microcystin-producing
      cyanobacteria Microcystis aeruginosa. The method has been used to detect the
      presence of these pathogenic bacteria in water and inside free living amoeba. Its
      validation in 72 samples obtained from different water sources from Aragon
      (Spain) evidences that Mycobacterium and Pseudomonas spp are prevailing as amoeba
      resistant bacteria.

PMID- 23168311
TI  - Combined isotope and enantiomer analysis to assess the fate of phenoxy acids in a
      heterogeneous geologic setting at an old landfill.
AB  - Phenoxy acid herbicides and their potential metabolites represent industrial or
      agricultural waste that impacts groundwater and surface waters through leaching
      from old landfills throughout the world. Fate assessment of dichlorprop and its
      putative metabolite 4-CPP (2-(4-chlorophenoxy)propionic acid) is frequently
      obstructed by inconclusive evidence from redox conditions, heterogeneous geologic
      settings (e.g. clay till) and ambiguous parent-daughter relationships (i.e. 4-CPP
      may be daughter product or impurity of dichlorprop). For the first time, a
      combination of four methods was tested to assess transformation of phenoxy acids
      at a contaminated landfill (Risby site): analysis of (i) parent and daughter
      compound concentrations, (ii) enantiomer ratios (iii) compound-specific isotope
      analysis and (iv) enantiomer-specific isotope analysis. Additionally, water
      isotopes and chloride were used as conservative tracers to delineate two distinct
      groundwater flow paths in the clay till. Metabolite concentrations and isotope
      ratios of chlorinated ethenes demonstrated dechlorination activity in the area
      with highest leachate concentrations (hotspot) indicating favorable conditions
      also for dechlorination of dichlorprop to 4-CPP and further to phenoxypropionic
      acid. Combined evidence from concentrations, enantiomer ratios and isotope ratios
      of dichlorprop and 4-CPP confirmed their dechlorination in the hotspot and gave
      evidence for further degradation of 4-CPP downgradient of the hotspot. A
      combination of 4-CPP enantiomer and isotope analysis indicated different
      enantioselectivity and isotope fractionation, i.e. different modes of 4-CPP
      degradation, at different locations. This combined information was beyond the
      reach of any of the methods applied alone demonstrating the power of the new
      combined approach.

PMID- 23168312
TI  - Reaction of benzophenone UV filters in the presence of aqueous chlorine: kinetics
      and chloroform formation.
AB  - The transformation of two benzophenone UV filters (Oxybenzone and Dioxybenzone)
      was examined over the pH range 6-11 in the presence of excess aqueous chlorine.
      Under these conditions, both UV filters were rapidly transformed by aqueous
      chlorine just above circumneutral pH while transformation rates were
      significantly lower near the extremes of the pH range investigated. Observed
      first-order rate coefficients (k(obs)) were obtained at each pH for aqueous
      chlorine concentrations ranging from 10 to 75 MUM. The k(obs) were used to
      determine the apparent second-order rate coefficient (k(app)) at each pH
      investigated as well as determine the reaction order of aqueous chlorine with
      each UV filter. The reaction of aqueous chlorine with either UV filter was found
      to be an overall second-order reaction, first-order with respect to each
      reactant. Assuming elemental stoichiometry described the reaction between aqueous
      chlorine and each UV filter, models were developed to determine intrinsic rate
      coefficients (k(int)) from the k(app) as a function of pH for both UV filters.
      The rate coefficients for the reaction of HOCl with 3-methoxyphenol moieties of
      oxybenzone (OXY) and dioxybenzone (DiOXY) were k(1,OxY) = 306 +/- 81 M-1s-1 and
      k(1,DiOxY) = 154 +/- 76 M-1s-1, respectively. The k(int) for the reaction of
      aqueous chlorine with the 3-methoxyphenolate forms were orders of magnitude
      greater than the un-ionized species, k(2,OxY) = 1.03(+/-0.52) * 106 M-1s-1 and
      k(2_1,DiOxY) = 4.14(+/-0.68) * 105 M-1s-1. Also, k(int) for the reaction of
      aqueous chlorine with the DiOXY ortho-substituted phenolate moiety was
      k(2_2,DiOxY) = 2.17(+/-0.30) * 103 M-1s-1. Finally, chloroform formation
      potential for OXY and DiOXY was assessed over the pH range 6-10. While chloroform
      formation decreased as pH increased for OXY, chloroform formation increased as pH
      increased from 6 to 10 for DiOXY. Ultimate molar yields of chloroform per mole of
      UV filter were pH dependent; however, chloroform to UV filter molar yields at pH
      8 were 0.221 CHCl3/OXY and 0.212 CHCl3/DiOXY.

PMID- 23168313
TI  - Data sources for heart failure comparative effectiveness research.
AB  - Existing data sources for heart failure research offer advantages and
      disadvantages for CER. Clinical registries collect detailed information about
      disease presentation, treatment, and outcomes on a large number of patients and
      provide the "real-world" population that is the hallmark of CER. Data are not
      collected longitudinally, however, and follow-up is often limited. Large
      administrative datasets provide the broadest population coverage with
      longitudinal outcomes follow-up but lack clinical detail. Linking clinical
      registries with other databases to assess longitudinal outcomes holds great
      promise. The Federal Coordinating Council for Comparative Effectiveness Research
      recommends further efforts on longitudinal linking of administrative or EHR-based
      databases, patient registries, private sector databases (particularly those with
      commercially insured populations that are not covered under federal and state
      databases), and other relevant data sources containing pharmacy, laboratory,
      adverse events, and mortality information. Advancing the infrastructure to
      provide robust, scientific data resources for patient-centered CER must remain a
      priority.

PMID- 23168315
TI  - Epidemiologic and statistical methods for comparative effectiveness research.
AB  - Observational methods are evolving in response to the widespread availability of
      data from clinical registries, electronic health records, and administrative
      databases. These approaches will never eliminate the need for randomized trials,
      but clearly have a role in evaluating the effect of therapies in unselected
      populations treated in routine practice.

PMID- 23168314
TI  - End points for comparative effectiveness research in heart failure.
AB  - CER for heart failure continues to evolve, including its assessment of end
      points. Reliance on surrogate end points is unacceptable as a means of
      definitively establishing comparisons of clinical effectiveness. CER needs to
      focus on measures that clearly reflect clinical effectiveness and safety, not
      just survival but also standardized assessments of health status and detailed
      resource utilization, and it must do so in a standardized way to allow for
      comparison. This strategy almost certainly requires increased reliance on
      prospective studies with proactive end-point capture, preferably in the setting
      of randomized allocation of the interventions being compared.

PMID- 23168316
TI  - Comparative effectiveness research: drug-drug comparisons in heart failure.
AB  - Drug-drug CER is valuable when applied to the right question using the right
      methods in a relevant context. Being aware of limitations and strengths, and
      incorporating these insights into the interpretation of results is crucial.
      Rigorously performed drug-drug CER can help guide clinical practice and future
      research in HF.

PMID- 23168317
TI  - Heart failure patient adherence: epidemiology, cause, and treatment.
AB  - Poor adherence to therapeutic regimens is a significant impediment to improving
      clinical outcomes in the HF population. Typical rates of adherence to prescribed
      medications, low-sodium diets, and aerobic exercise programs remain lower than
      that needed to decrease morbidity and mortality associated with HF. Factors
      contributing to poor adherence include multiple comorbidities, clinical
      depression, and decreased cognitive functioning. HF education and programs to
      enhance self-management skills have improved patient quality of life but have yet
      to decrease mortality or rehospitalization rates significantly. Telemonitoring to
      improve adherence behaviors and self-management interventions within broader HF
      management programs have demonstrated significant clinical improvements in this
      population.

PMID- 23168318
TI  - Effectiveness of implantable cardioverter defibrillators and cardiac
      resynchronization therapy in heart failure.
AB  - Randomized trials and observational data have consistently demonstrated the
      benefit of ICDs for primary prevention of SCD in patients with HF and LVSD or
      secondary prevention in patients with a history of prior ventricular arrhythmias
      or aborted SCD, most of whom have HF. Secondary and post hoc analyses of trial
      data, as well as observational data, generally suggest that ICD therapy is
      effective in most selected subpopulations, such as the elderly and patients with
      NYHA class IV HF symptoms, but some studies suggest that ICDs may not be as
      effective in women and those with severe comorbidities, such as ESRD. Although
      there is limited evidence for an incremental benefit achieved with dual-chamber
      compared with single-chamber ICDs, the former devices are placed almost twice as
      frequently in the United States. Finally, observational data have recently shown
      that ICD procedural outcomes are improved when the device is placed by an
      electrophysiologist and at a high-volume hospital. More recently, clinical trials
      have demonstrated that cardiac resynchronization therapy improves quality of life
      and lowers rates of HF hospitalization in patients with symptomatic HF, LVSD, and
      a prolonged QRS complex already receiving optimal medical management; recent
      trial results have also suggested a mortality benefit with CRT in this
      population. In addition, recent trial data suggest that CRT reduces nonfatal
      events among mildly symptomatic patients (NYHA class I-II); however, the cost
      effectiveness of CRT in this population remains unclear. As with ICDs, secondary
      and post hoc analyses of trial data as well as observational data suggest that
      CRT remains effective in most selected subpopulations, including stable NYHA
      class IV patients, the very elderly, and women. Recent observational work has
      suggested that CRT may not benefit patients with an RBBB QRS morphology to the
      same extent as those with an LBBB pattern, although because more conclusive
      studies are currently lacking, the guidelines do not tailor the recommendations
      based on QRS morphology. In summary, ICDs, CRT-P, and CRT-D represent important
      and effective treatment modalities for select patients with HF. Additional
      investigation is required to better determine which patient populations most
      benefit from these cardiac devices and which device, implanting physician, and
      hospital characteristics optimize outcomes with these cardiac devices.

PMID- 23168320
TI  - The economics of heart failure.

PMID- 23168319
TI  - Comparative effectiveness research in heart failure therapies: women, elderly
      patients, and patients with kidney disease.

PMID- 23168321
TI  - Comparative effectiveness research in heart failure.

PMID- 23168322
TI  - Bi-planar image segmentation based on variational geometrical active contours
      with shape priors.
AB  - This work proposes an image segmentation model based on active contours. For a
      better handling of regions where anatomical structures are poorly contrasted
      and/or missing, we propose to incorporate a priori shape information in a
      variational formulation. Based on a level set approach, the proposed functional
      is composed of four terms. The first one makes the level set keep the important
      signed distance function property, which is necessary to guarantee the good level
      set evolution. Doing so results in avoiding the classical re-initialization
      process, contrary to most existing works where a partial differential equation is
      used instead. The second energy term contains the a priori information about
      admissible shapes of the target object, the latter being integrated in the level
      set evolution. An energy that drives rapidly the level set towards objects of
      interest is defined in the third term. A last term is defined on prior shapes
      thanks to a complete and modified Mumford-Shah model. The segmentation model is
      derived by solving the Euler-Lagrange equations associated to the functional
      minimization. Efficiency and robustness of our segmentation model are validated
      on synthetic images, digitally reconstructed images, and real image radiographs.
      Quantitative evaluations of segmentation results are also provided, which also
      show the importance of prior shapes in the context of image segmentation.

PMID- 23168323
TI  - Simple method to measure volume difference in asymmetric and hypoplastic breasts.

PMID- 23168324
TI  - Deleterious effects of soluble beta amyloid on cognition, antagonism by saline
      and noradrenaline, a role for microglia.
AB  - Small oligomeric beta amyloid (Abeta(1-42)) injected 45 min prior to single-trial
      bead discrimination training resulted in impaired learning in day-old chickens. A
      new experimental protocol was used where the injections of drugs were at times
      around the time of injection of Abeta. It was found that the Na(+) levels of the
      saline used to dissolve Abeta affected cognitive impairment. Na(+) levels above
      the normal plasma value (140 mM) reduced Abeta-induced learning deficits whereas
      levels below increased sensitivity to Abeta. The new protocol was also used to
      examine the ability of certain noradrenergic adrenoceptor antagonist and
      agonists, insulin, glucose and minocycline to reduce learning disruption caused
      by Abeta. The drugs (made up in 154 mM sodium chloride) were injected before, at
      the same time or after the injection of Abeta and although all drugs prevented
      Abeta-induced disruption of learning when given in the same injection as Abeta,
      some injected before could prevent Abeta disrupting learning, whereas others
      could rescue learning ability when given after Abeta injection. These results are
      interpreted in the light of possible actions of noradrenaline on microglia and
      various processes: astrocytic metabolism, cerebral microcirculation, and removal
      of Abeta away from the site of injection. The possible importance of
      hypernatremia and hyponatremia in the incidence of Alzheimer's disease is
      discussed.

PMID- 23168325
TI  - Repeated exposure to a tone transiently alters spectral tuning bandwidth of
      neurons in the central nucleus of inferior colliculus in juvenile rats.
AB  - Early acoustic experience changes tonal frequency tuning in the inferior
      colliculus (IC) and the primary auditory cortex. The contributions of IC
      plasticity to cortical frequency map reorganization are not entirely clear. While
      most cortical plasticity studies exposed animals to pulsed tones, studies of IC
      plasticity used either noise or a continuous tone. Here we compared the effects
      of repeated exposure to single-frequency tone pips on cortical and IC frequency
      representations in juvenile rats. We found that while tone exposure caused a long
      lasting increase in cortical representations of the exposure frequency, changes
      to IC neurons were limited to a transient narrowing of tuning bandwidth. These
      results suggest that previously documented cortical frequency map reorganization
      does not depend on similar changes in the subcortical auditory nuclei.

PMID- 23168326
TI  - Mirror exposure in women with bulimic symptoms: how do thoughts and emotions
      change in body image treatment?
AB  - Mirror exposure is an efficient treatment for body image problems in eating
      disorders. Although habituation processes and cognitive changes are postulated to
      be underlying mechanisms, evidence is scarce, especially during repeated mirror
      exposure treatment. Fourteen participants with eating disorders not otherwise
      specified (EDNOS) and five with bulimia nervosa (BN) composed the bulimic group
      (BG), and 19 healthy women without any mental disorder composed the healthy
      controls group (HC). The participants were treated by four standardized mirror
      exposure sessions. Subjective distress was assessed five times during each
      session. Both negative and positive emotions and negative thoughts were assessed
      after each session. The patients in the BG reported significantly higher levels
      of negative emotions and cognitions than did those in the HC in all measures and
      across all sessions. In both groups, subjective distress increased significantly
      within each session and decreased toward the end of each session. Only in the
      subjects of the BG group did both distress and negative thoughts and emotions
      decrease significantly from session to session, whereas positive emotions
      increased. The patterns of change differed between the BG and the HC, suggesting
      that habituation between sessions occurred only in the BG. Our findings suggest
      that the additional underlying cognitive-affective processes merit further
      investigation.

PMID- 23168327
TI  - Cognitive-behavior therapy resolves implicit fear associations in generalized
      anxiety disorder.
AB  - BACKGROUND: Cognitive schema theories postulate that anxiety disorders are
      associated with excessive fear associations in memory. For generalized anxiety
      disorder (GAD), it has been shown that patients not only exhibit negative
      implicit evaluations of clearly negative worry words (e.g., cancer), but also a
      generalization of this effect to neutral words (e.g., diagnosis). This study
      assessed the sensitivity of this bias, which has been interpreted as an indicator
      of a pathologically broadened fear structure, to cognitive-behavioral therapy
      (CBT). METHODS: An Extrinsic Affective Simon task was used to measure implicit
      associations with idiosyncratic neutral and negative worry words in 23 GAD
      patients and 25 healthy controls (HC). Patients were tested before and after CBT,
      and half of them were additionally tested while waiting for treatment. Clinical
      symptoms were measured before and after treatment, and at 6-months follow-up.
      RESULTS: CBT normalized bias for neutral words, and the extent of bias reduction
      during treatment predicted the extent of additional symptom improvement during
      the 6 months following intervention. Furthermore, the amplitude of pre-treatment
      bias predicted the onset of CBT response, with lower bias predicting immediate
      symptom improvement at the end of treatment, and higher bias predicting delayed
      treatment effects during the 6 months follow-up. CONCLUSIONS: Biased implicit
      evaluation of neutral worry targets does not represent an enduring vulnerability
      factor for the development of GAD but is related to heightened levels of state
      worry. Furthermore, the normalization of this bias might be a crucial factor in
      the therapeutic action of CBT.

PMID- 23168328
TI  - Effects of tic suppression: ability to suppress, rebound, negative reinforcement,
      and habituation to the premonitory urge.
AB  - The comprehensive behavioral intervention for tics (CBIT) represents a safe,
      effective non-pharmacological treatment for Tourette's disorder that remains
      underutilized as a treatment option. Contributing factors include the perceived
      negative consequences of tic suppression and the lack of a means through which
      suppression results in symptom improvement. Participants (n = 12) included youth
      ages 10-17 years with moderate-to-marked tic severity and noticeable premonitory
      urges who met Tourette's or chronic tic disorder criteria. Tic frequency and urge
      rating data were collected during an alternating sequence of tic freely or
      reinforced tic suppression periods. Even without specific instructions regarding
      how to suppress tics, youth experienced a significant, robust (72%), stable
      reduction in tic frequency under extended periods (40 min) of contingently
      reinforced tic suppression in contrast to periods of time when tics were ignored.
      Following periods of prolonged suppression, tic frequency returned to pre
      suppression levels. Urge ratings did not show the expected increase during the
      initial periods of tic suppression, nor a subsequent decline in urge ratings
      during prolonged, effective tic suppression. Results suggest that environments
      conducive to tic suppression result in reduced tic frequency without adverse
      consequences. Additionally, premonitory urges, underrepresented in the
      literature, may represent an important enduring etiological consideration in the
      development and maintenance of tic disorders.

PMID- 23168329
TI  - The association between dairy product consumption and cognitive function in the
      National Health and Nutrition Examination Survey.
AB  - The present cross-sectional study sought to determine the potential relationships
      between the intake of dairy foods (total dairy products, milk and cheese) and
      cognitive function through information garnered in the National Health and
      Nutrition Examination Surveys (1988-94 and 1999-2002). Cognitive measures of
      vasomotor speed, coding speed and immediate memory recall were assessed from a
      simple reaction time task (SRTT), symbol-digit substitution test (SDST) and
      serial digit learning task, respectively, in adults 20-59 years of age. A
      summation of the percentile rank scores on each of the three tests provided a
      measure of overall cognitive function. In adults 60 years of age and above, a
      story recall test and a digit-symbol substitution test (DSST) were utilised to
      determine cognitive function in an elderly population. The results indicated that
      cognitive scores for the SRTT were not different between consumers and non
      consumers of dairy foods. However, there were associations observed between 20-
      and 59-year-old consumers of total dairy foods and a higher SDST percentile score
      (53.2 (SE 1.3) to 49.4 (SE 2.0)) and a calculated global cognitive percentile
      score (53.3 (SE 1.1) to 50.2 (SE 1.4)) compared with non-consumers. A similar
      significant association was observed with cheese consumers. In adults over 60
      years of age, an association between total dairy product consumption and higher
      DSST percentile scores (51.5 (SE 1.9) to 46.2 (se 3.0)) was also observed. These
      findings highlight the need for additional research on how dairy products may
      affect cognition and by what mechanisms, through its nutrients or other
      components.

PMID- 23168330
TI  - Genetic susceptibility to dioxin-like chemicals' induction of cytochrome P4501A2
      in the human adult linked to specific AhRR polymorphism.
AB  - BACKGROUND: Dioxin-like chemicals are known to exert their effect by binding to
      aryl hydrocarbon receptor (AhR), forming complexes with aryl hydrocarbon nuclear
      translocator (ARNT), and binding to dioxin responsive elements (DREs) in promoter
      region to regulate the transcription of specific genes. In a previous study of
      the Yucheng cohort of humans who were exposed to high toxic levels of dioxin-like
      chemicals (PCDFs and PCBs), we reported marked induction of cytochrome P450 1A2
      (CYP1A2) activity and this induction was an excellent biomarker of the exposure
      and adverse human health effects seen in the Yucheng cohort. OBJECTIVES: The goal
      of this study was to determine the relationship between inducibility of CYP1A2
      and genetic polymorphisms of AhR, ARNT, and AhRR in human. METHODS: The Yucheng
      victims who completed blood sample collecting in 1994-1995 for serum
      concentrations of PCB, PCDF, and PCDD congeners, and also completed the caffeine
      breath tests for CYP1A2 activity were identified. From the collected blood
      samples, six single nucleotide polymorphisms were selected for genotyping,
      including AhR (rs2066853), AhRR (rs2292596), ARNT (rs7517566), ARNT (rs3820541),
      ARNT (rs3768016), and ARNT (rs2228099). RESULTS: AhRR (rs2292596) polymorphism
      was significantly related to CYP1A2 inducibility (p=0.01). A linear trend test
      was observed between people with AhRR (rs2292596) GG, GC, and CC genotype
      (p=0.0014). CONCLUSION: Overall, AhRR (rs2292596) genotypes predict the
      inducibility of CYP1A2 in people highly exposed to toxic dioxin-like chemicals.
      Future studies and analysis will determine to what degree these polymorphisms can
      predict a human's susceptibility to dioxin-related adverse human health effects.

PMID- 23168331
TI  - Spatial trends of organochlorinated pesticides, polychlorinated biphenyls, and
      polybrominated diphenyl ethers in Atlantic Anguillid eels.
AB  - The bioaccumulation of lipophilic contaminants such as polychlorinated biphenyls
      (PCBs), organochlorine pesticides (OCPs), and polybrominated diphenyl ethers
      (PBDEs) can result in a reduction in fitness and spawner quality in eels and may
      be a factor in Anguillid sp. population declines. Contaminant concentrations in
      eels have been studied extensively in Europe, but data for American eels are
      severely lacking. Concentrations of PCBs, OCPs, and PBDEs were determined in
      American eel from eastern Canada and New York, USA, along with European eel from
      Belgium. Principal component analysis revealed that eels captured in the St.
      Lawrence estuary were a mixture of upstream migrants from the St. Lawrence River
      watershed, and fish captured in local tributaries. Contaminant concentrations
      were dependent on origin, related to the local environment, and were lower than
      historic values. In Canada, concentrations of OCPs and PCBs in eel tissues were
      below the Canadian human consumption guidelines for contaminants in fish,
      indicating that the current risk to consumers is low. However, concentrations of
      PCBs, total DDT, and mirex in eels from L. Ontario and the upper St. Lawrence R.
      were above Great Lakes guidelines for the protection of piscivorous predators.
      Concentrations of penta-BDE homologs exceeded the Canadian guideline for
      environmental quality in over half of the eels in this study, but concentrations
      of the other homolog groups were below the guideline.

PMID- 23168332
TI  - The personal and professional: nurses' lived experiences of adoption.
AB  - BACKGROUND: Nurses provide healthcare services to members of the adoption triad
      (AT; birth parents, adoptive parents, and the child) in a number of settings.
      However, nurses' perceptions of and interactions with members of the AT have not
      been investigated. PURPOSE: This study describes the lived experiences of nurses
      and the care rendered to the AT using a descriptive phenomenological approach.
      METHOD: In response to an invitation published in a national electronic
      newsletter, nurses were asked to submit narratives about their experiences in
      caring for members of the AT. Researchers coded 17 narratives using Colaizzi's
      phenomenological method. RESULTS: Four themes emerged from the texts: (1) Where
      the personal and professional selves meet ("I see so many issues from both
      sides"); (2) The paradox of adoption ("...an emotional rollercoaster"); (3)
      Unique contexts of adoptive families ("We all have a story"); and (4) Reframing
      nurses' perceptions surrounding adoption ("There are several areas we could
      improve"). CLINICAL IMPLICATIONS: Nurses often have a personal connection to
      adoption and this potentiates the care delivered to AT members. Serving as role
      models for their peers and advocates for a better understanding of the dynamics
      of relinquishment and placement, nurses can improve clinical practices for these
      patients. CONCLUSIONS: Themes reflected insights gained from both personal and
      professional roles and offer specific interventions that enhance care of the AT.
      Nursing education and practice guidelines should include care rendered to the AT.

PMID- 23168333
TI  - AdS/CFT applications to relativistic heavy-ion collisions: a brief review.
AB  - We review some of the recent progress in our understanding of the physics of
      ultrarelativistic heavy-ion collisions due to applications of AdS/CFT
      correspondence.

PMID- 23168334
TI  - Gene variants within the COL1A1 gene are associated with reduced anterior
      cruciate ligament injury in professional soccer players.
AB  - OBJECTIVES: To examine the association of the COL1A1 -1997G/T and +1245G/T
      polymorphisms, individually and as haplotypes, with anterior cruciate ligament
      ruptures in professional soccer players. DESIGN: Subjects were 91 male
      professional soccer players with surgically diagnosed primary anterior cruciate
      ligament ruptures. The control group consisted of 143 apparently healthy male
      professional soccer players, who were without any self-reported history of
      ligament or tendon injury. Both subjects and healthy controls are from the same
      soccer teams, of the same ethnicity (Polish, East-Europeans for >=3 generations),
      a similar age category, and had a comparable level of exposure to anterior
      cruciate ligament injury. METHODS: Genomic DNA was extracted from the oral
      epithelial cells using GenElute Mammalian Genomic DNA Miniprep Kit (Sigma,
      Germany). All samples were genotyped using a Rotor-Gene real-time polymerase
      chain reaction. RESULTS: Genotype distributions for both polymorphisms met the
      Hardy-Weinberg expectations in both subjects and controls (p>0.05). Higher
      frequency of the COL1A1 G-T (-1997G/T and +1245G/T polymorphisms) haplotype was
      significantly associated with reduced risk for anterior cruciate ligament rupture
      (Hap.score -1.98, p=0.048). The TT genotype was under-represented in the anterior
      cruciate ligament rupture group. However, this result was not statistically
      significant (p=0.084 Fisher's exact test, recessive mode: TT vs GT+GG).
      CONCLUSIONS: Higher frequency of the COL1A1 G-T haplotype is associated with
      reduced risk of anterior cruciate ligament injury in a group of professional
      soccer players. Consequently, carrying two copies the COL1A1 G-T haplotype may be
      protective against anterior cruciate ligament injury.

PMID- 23168335
TI  - Myosin phosphatase modulates the cardiac cell fate by regulating the subcellular
      localization of Nkx2.5 in a Wnt/Rho-associated protein kinase-dependent pathway.
AB  - RATIONALE: Nkx2.5 is a transcription factor that regulates cardiomyogenesis in
      vivo and in embryonic stem cells. It is also a common target in congenital heart
      disease. Although Nkx2.5 has been implicated in the regulation of many cellular
      processes that ultimately contribute to cardiomyogenesis and morphogenesis of the
      mature heart, relatively little is known about how it is regulated at a
      functional level. OBJECTIVE: We have undertaken a proteomic screen to identify
      novel binding partners of Nkx2.5 during cardiomyogenic differentiation in an
      effort to better understand the regulation of its transcriptional activity.
      METHODS AND RESULTS: Purification of Nkx2.5 from differentiating cells identified
      the myosin phosphatase subunits protein phosphatase 1beta and myosin phosphatase
      targeting subunit 1 (Mypt1) as novel binding partners. The interaction with
      protein phosphatase 1 beta/Mypt1 resulted in exclusion of Nkx2.5 from the nucleus
      and, consequently, inhibition of its transcriptional activity. Exclusion of
      Nkx2.5 was inhibited by treatment with leptomycin B and was dependent on an Mypt1
      nuclear export signal. Furthermore, in transient transfection experiments, Nkx2.5
      colocalized outside the nucleus with phosphorylated Mypt1 in a manner dependent
      on Wnt signaling and Rho-associated protein kinase. Treatment of differentiating
      mouse embryonic stem cells with Wnt3a resulted in enhanced phosphorylation of
      endogenous Mypt1, increased nuclear exclusion of endogenous Nkx2.5, and a failure
      to undergo terminal cardiomyogenesis. Finally, knockdown of Mypt1 resulted in
      rescue of Wnt3a-mediated inhibition of cardiomyogenesis, indicating that Mypt1 is
      required for this process. CONCLUSIONS: We have identified a novel interaction
      between Nkx2.5 and myosin phosphatase. Promoting this interaction represents a
      novel mechanism whereby Wnt3a regulates Nkx2.5 and inhibits cardiomyogenesis.

PMID- 23168337
TI  - Symptom clusters in patients with head and neck cancer receiving concurrent
      chemoradiotherapy.
AB  - OBJECTIVES: This study is to identify symptom clusters for head and neck (HNC)
      patients treated with concurrent chemoradiotherapy. PATIENTS AND METHODS: A
      secondary data analysis of 684 HNC patients treated on the Radiation Therapy
      Oncology Group (RTOG) 0129 trial comparing different RT fractionation schedules
      with concurrent chemotherapy was used to examine clusters. Treatment-related
      symptoms were measured by clinicians at three time-points during and after
      chemoradiotherapy using the National Cancer Institute Common Toxicity Criteria
      v2.0. Exploratory factor analysis was applied to identify symptom clusters, which
      was further verified by confirmatory factor analysis. Coefficients of congruence
      and alpha coefficients were employed to examine generalizability of cluster
      structures over different time-points and in different subgroups. RESULTS: Two
      clusters were identified. The HNC specific cluster is composed of
      radiodermatitis, dysphagia, radiomucositis, dry mouth, pain, taste disturbance,
      and fatigue. The gastrointestinal (GI) cluster involves nausea, vomiting, and
      dehydration. With the exception of patients 65years old or older, diagnosed with
      larynx cancer, or with stage III cancer, the two clusters were generalizable to
      different subgroups defined by age, gender, race, education, marital status,
      history of tobacco use, treatments, primary sites, disease stages, and tube
      feedings, as well as to the three symptom assessment time-points. CONCLUSIONS:
      The data provides preliminary support for two stable clusters in patients with
      HNC. These findings may serve to inform the symptom management in clinical
      practice. Moreover, the findings necessitate future research to examine the
      generalizability of identified clusters in the late symptom phase or other
      treatment modalities, and to understand the underlying biological mechanism.

PMID- 23168338
TI  - Anisotropic fatigue behavior of human enamel characterized by multi-cycling
      nanoindentation.
AB  - Single- and multi-cycling nanoindentations were performed on occlusal surface and
      axial section of human enamel rod using Berkovich indenter. Deviation of load
      depth curve under multi-cycle from single-cycle could indicate the anisotropic
      fatigue damage during repeated indentations. On occlusal surface, fatigue damage
      is ascribed to the partial interface debonding between crystals and protein and
      incomplete refolding of domain bonds of protein molecules. While on the axial
      section, additional damages, i.e., fracture of crystals and debonding at the end
      of crystals are supposed to be dominant.

PMID- 23168336
TI  - Phosphodiesterase type 3A regulates basal myocardial contractility through
      interacting with sarcoplasmic reticulum calcium ATPase type 2a signaling
      complexes in mouse heart.
AB  - RATIONALE: cAMP is an important regulator of myocardial function, and regulation
      of cAMP hydrolysis by cyclic nucleotide phosphodiesterases (PDEs) is a critical
      determinant of the amplitude, duration, and compartmentation of cAMP-mediated
      signaling. The role of different PDE isozymes, particularly PDE3A vs PDE3B, in
      the regulation of heart function remains unclear. OBJECTIVE: To determine the
      relative contribution of PDE3A vs PDE3B isozymes in the regulation of heart
      function and to dissect the molecular basis for this regulation. METHODS AND
      RESULTS: Compared with wild-type littermates, cardiac contractility and
      relaxation were enhanced in isolated hearts from PDE3A(-/-), but not PDE3B(-/-),
      mice. Furthermore, PDE3 inhibition had no effect on PDE3A(-/-) hearts but
      increased contractility in wild-type (as expected) and PDE3B(-/-) hearts to
      levels indistinguishable from PDE3A(-/-). The enhanced contractility in PDE3A(-/
      ) hearts was associated with cAMP-dependent elevations in Ca(2+) transient
      amplitudes and increased sarcoplasmic reticulum (SR) Ca(2+) content, without
      changes in L-type Ca(2+) currents of cardiomyocytes, as well as with increased SR
      Ca(2+)-ATPase type 2a activity, SR Ca(2+) uptake rates, and phospholamban
      phosphorylation in SR fractions. Consistent with these observations, PDE3
      activity was reduced ~8-fold in SR fractions from PDE3A(-/-) hearts.
      Coimmunoprecipitation experiments further revealed that PDE3A associates with
      both SR calcium ATPase type 2a and phospholamban in a complex that also contains
      A-kinase anchoring protein-18, protein kinase type A-RII, and protein phosphatase
      type 2A. CONCLUSIONS: Our data support the conclusion that PDE3A is the primary
      PDE3 isozyme modulating basal contractility and SR Ca(2+) content by regulating
      cAMP in microdomains containing macromolecular complexes of SR calcium ATPase
      type 2a-phospholamban-PDE3A.

PMID- 23168339
TI  - Myxobacterial metabolites enhance cell proliferation and reduce intracellular
      stress in cells from a Parkinson's disease mouse model.
AB  - Parkinson's disease is a degenerative disorder of the central nervous system and
      is regarded as one of the most common neurologic diseases. Myxobacterial
      metabolites have been shown to possess a wide range of beneficial physiological
      effects, including anti-fungal, antibiotic, and anti-tumor activities. We aimed
      to determine whether myxobacterial metabolites exhibit a potential therapeutic
      effect in cells from a Parkinson's disease mouse model. The screening process
      identified 4 compounds, which were found to increase cell growth rate by >1.3
      times that observed on the vehicle. These compounds promoted regeneration of the
      cells from a Parkinson's mouse model following the appearance of acute lesions,
      and reduced the levels of proteins associated with endoplasmic reticulum stress
      and apoptotic cell death. These compounds could lead to the development of novel
      therapies for Parkinson's disease and provide insight into the mechanisms through
      which apoptotic cell death takes place in this disorder.

PMID- 23168342
TI  - Hierarchical regression and structural equation modeling: two useful analyses for
      life course research.
AB  - This article reviews the life course perspective and considers various life
      course hypotheses such as trajectories, transitions, critical periods,
      sequencing, duration, and cumulative effects. Hierarchical regression and
      structural equation modeling are suggested as analyses to use in life course
      research. Secondary analysis was performed on the Early Head Start Research and
      Evaluation Study, 1996-2010, to illustrate their strengths and challenges. Models
      investigated the influence of mother and infant characteristics and of parent
      child dysfunction at 14 and 24 months to children's cognitive outcomes at 36
      months. Findings were interpreted and discussed in the context of life course
      hypotheses.

PMID- 23168343
TI  - Evaluating primary care delivery systems for an uninsured Hispanic immigrant
      population.
AB  - Hispanic populations experience disparities in health outcomes and health care.
      Using participatory methods, we evaluated 4 systems of primary care delivery for
      an uninsured Hispanic population. Best practices were determined that could be
      translated back to the partner clinics and the community. The assessment included
      patient service areas, provider discussion groups, patient surveys, calculation
      of travel distances, and costs. The following best practices were identified:
      improved proximity to services, enhanced bilingual services, affordable services,
      and integrated services. Researchers and providers not only identified
      translatable service delivery practices but also laid the foundation for ongoing
      research partnerships.

PMID- 23168344
TI  - Using qualitative inquiry and participatory research approaches to develop
      prevention research: validating a life course perspective.
AB  - Application of life course theory (LCT) holds promise for advancing knowledge
      toward the elimination of health disparities. This article validates the
      usefulness of employing a life course perspective when conducting health
      disparities research. We provide an overview of LCT as it applies to our research
      program in prevention of human immunodeficiency virus (HIV) among Latino teen
      parents. We illustrate the goodness-of-fit of our research with the basic
      premises of LCT. Though early adverse life experiences impact health over the
      lifespan, strength-based HIV prevention programs designed for Latino teen parents
      that recognize the reality of their lives may alter their health trajectory.

PMID- 23168345
TI  - Understanding the day-to-day lives of obese children and their families.
AB  - This study investigated the daily lives of obese children and their families to
      better understand factors influencing weight-related behaviors. A multiple case
      study design was implemented with 6 obese children and their families.
      Participant observations occurred in different settings from when the children
      woke until they went to bed, yielding approximately 95 hours of data per family.
      Lack of parenting skills and role modeling, environments encouraging poor weight
      related behaviors, low self-awareness and enjoyment of sedentary activities were
      common themes. Child obesity involves a complex set of factors interacting to
      place a child at risk of developing weight problems.

PMID- 23168347
TI  - A true challenge for any superhero: an evaluation of a comic book obesity
      prevention program.
AB  - The purpose of this study was to pilot test the Comics for Health program, a
      theory-based nutrition and physical activity intervention for children. Twelve
      after-school programs were randomized to either a theory-based (n = 37) or a
      knowledge-based (n = 34 children) version of the intervention. Pretests,
      posttests, and 3-month follow-up tests were administered to evaluate the
      programmatic effects on body mass index percentile, obesity-related behaviors,
      and constructs of social cognitive theory. Both interventions found significant,
      yet modest effects for fruit and vegetable consumption (P < .005), physical
      activities (P < .004), and water and sugar-free beverage consumption (P < .001)
      and self-efficacy for fruit and vegetable consumption (P < .015) and physical
      activities (P < .009).

PMID- 23168346
TI  - A life course perspective on stress and health among caregivers of children with
      asthma in Detroit.
AB  - Low-income caregivers raising children with asthma experience many obstacles to
      their own health, including stress. To understand and describe their daily
      experiences, researchers conducted 40 qualitative interviews supplemented with
      descriptive quantitative surveys in Detroit, Michigan, as part of a community
      based participatory research partnership of Community Action Against Asthma.
      Prevalence of chronic illness is noticeably higher among participants than the
      general US population. Caregivers identified stress processes that may influence
      disproportionate health outcomes and risk-related behaviors over their lifetime.
      Applying a life course perspective, findings suggest that public health
      interventions should address family-level comorbidities, increase instrumental
      social support, and acknowledge practical coping mechanisms.

PMID- 23168348
TI  - Determinants of parental perception and support on youth physical activity.
AB  - The study examines the impact of parental perception of children's weight and
      parental support on children's physical activity (PA) by weight groups.
      Multivariate regressions of parental perception of children's weight, parental
      support, and children's PA were conducted using parent-reported survey data.
      Results show that parental support was positively associated with children's PA.
      The impact of parental perception on children's PA and parenting behaviors varied
      depending on children's actual weight status. Parents may need more education and
      help to increase their knowledge about children's healthy weight and the problems
      associated with being outside the healthy weight zone.

PMID- 23168350
TI  - Left thoracotomy for coronary artery bypass grafting in a patient with an ileo
      coloplasty.

PMID- 23168351
TI  - Atrial fibrillation and the meaning of life.

PMID- 23168352
TI  - Bovine oviductal monolayers cultured under three-dimension conditions secrete
      factors able to release spermatozoa adhering to the tubal reservoir in vitro.
AB  - Different in vitro models have been developed to understand the interaction of
      gametes and embryos with the maternal reproductive tract. We recently showed that
      bovine oviductal monolayers three-dimensionally cultured in Gray's medium on
      collagen-coated microporous polycarbonate inserts under liquid-air interface
      conditions are well polarized, develop cilia, remain viable for at least 3 weeks
      postconfluence, and mantain the viability of bound spermatozoa significantly
      better than bidimensionally cultured monolayers. Herein, we used these culture
      conditions to understand whether: (1) spermatozoa adhering to three-dimensionally
      cultured oviductal monolayers can be released by heparin or penicillamine as
      previously shown with bidimensionally cultured oviductal monolayers and explants;
      and (2) media conditioned by three-dimensionally cultured oviductal monolayers
      were able to release spermatozoa adhering to oviductal explants. Findings
      demonstrated that (1) spermatozoa adhering to three-dimensionally cultured
      oviductal monolayers are readily released by heparin and penicillamine, (2) media
      conditioned by three-dimensionally cultured oviductal monolayers are able to
      release spermatozoa bound to oviductal explants, (3) do not depress sperm
      motility and viability, (4) they improve sperm kinetics, and (5) promote binding
      to the zona pellucida. In conclusion, in vitro data suggest that the release of
      spermatozoa adhering to the oviductal reservoir in vivo can be triggered by
      factors secreted by the oviduct itself that induce sperm capacitation.

PMID- 23168353
TI  - [Renal transplantation: ethical issues].
AB  - One of the most significant advances in medicine during the last 50 years is the
      development of organ transplantation. In the context of chronic kidney diseases,
      renal transplantation offers patients a better clinical outcome than other
      treatment options. However, the benefits of organ transplantation have not been
      maximized due to an inadequate supply of organs for transplantation. Despite the
      establishment of elaborate legal rules for organs procurement, both on deceased
      and living donors in numerous countries, ethical concerns remain. Most of them
      are consequences of the strategies implemented or proposed to address the so
      called organ shortage. The involvement of society in these complex problems is
      crucial as numerous questions emerge: could actual state of organ procurement
      change? Is it possible and/or realistic to increase the number of organs, with
      respects to living donors or deceased persons? Is the shortage an indicator to
      limit the use of kidney transplantation? How do we maintain efficiency and
      justice, in this context.

PMID- 23168354
TI  - Stochastic thermodynamics, fluctuation theorems and molecular machines.
AB  - Stochastic thermodynamics as reviewed here systematically provides a framework
      for extending the notions of classical thermodynamics such as work, heat and
      entropy production to the level of individual trajectories of well-defined non
      equilibrium ensembles. It applies whenever a non-equilibrium process is still
      coupled to one (or several) heat bath(s) of constant temperature. Paradigmatic
      systems are single colloidal particles in time-dependent laser traps, polymers in
      external flow, enzymes and molecular motors in single molecule assays, small
      biochemical networks and thermoelectric devices involving single electron
      transport. For such systems, a first-law like energy balance can be identified
      along fluctuating trajectories. For a basic Markovian dynamics implemented either
      on the continuum level with Langevin equations or on a discrete set of states as
      a master equation, thermodynamic consistency imposes a local-detailed balance
      constraint on noise and rates, respectively. Various integral and detailed
      fluctuation theorems, which are derived here in a unifying approach from one
      master theorem, constrain the probability distributions for work, heat and
      entropy production depending on the nature of the system and the choice of non
      equilibrium conditions. For non-equilibrium steady states, particularly strong
      results hold like a generalized fluctuation-dissipation theorem involving entropy
      production. Ramifications and applications of these concepts include optimal
      driving between specified states in finite time, the role of measurement-based
      feedback processes and the relation between dissipation and irreversibility.
      Efficiency and, in particular, efficiency at maximum power can be discussed
      systematically beyond the linear response regime for two classes of molecular
      machines, isothermal ones such as molecular motors, and heat engines such as
      thermoelectric devices, using a common framework based on a cycle decomposition
      of entropy production.

PMID- 23168356
TI  - Special issue in Hearing Research: neuroscience of tinnitus.

PMID- 23168355
TI  - Limb compressive load does not inhibit post activation depression of soleus H
      reflex in indiviudals with chronic spinal cord injury.
AB  - OBJECTIVE: We investigated the effect of various doses of limb compressive load
      on soleus H-reflex amplitude and post activation depression in individuals
      with/without chronic SCI. We hypothesized that SCI reorganization changes the
      typical reflex response to an external load. METHODS: Ten healthy adults and 10
      individuals with SCI received three doses of compressive load to the top of their
      knee (10%, 25%, and 50% of the body weight, BW). Soleus H-reflexes were measured
      before (baseline) and during the loading phase. RESULTS: With persistent
      background muscle activity across all testing sessions, segment compressive load
      significantly decreased post activation depression in the control group, but did
      not change the post activation ratio in the SCI group. Normalized H2 amplitude
      significantly increased according to load (50%> 25%> 10%) in the control group
      whereas was minimally modulated to load in those with SCI. CONCLUSIONS: Segment
      compressive load inhibits post activation depression in humans without SCI, but
      minimally modulates the reflex circuitry in people with chronic SCI. These
      findings suggest that spinal cord reorganization mitigates the typical response
      to load in people with chronic SCI. SIGNIFICANCE: Early limb load training may
      impact the reorganization of the spinal cord in humans with acute SCI.

PMID- 23168357
TI  - Gender differences in familiar voice identification.
AB  - We investigated gender differences in the identification of personally familiar
      voices in a gender-balanced sample of 40 listeners. From various types of
      utterances, listeners had to identify by name 20 speakers (10 female) among a set
      of 70 possible classmates who were all 12th grade pupils from the same local
      secondary school. Mean identification rates were 67% from sentences, and around
      35% for an isolated /Hello/ or a VCV syllable. Even from non-verbal harrumphs,
      speakers were identified with an accuracy of 18%, i.e. highly above chance
      levels. Substantial individual differences were observed between listeners.
      Importantly, superior overall performance of female listeners was qualified by an
      interaction between voice gender and listener gender. Male listeners exhibited an
      own-gender bias (i.e. better identification for male than female voices), whereas
      female listeners identified voices of both genders at similar levels. Individual
      own-gender identification biases were correlated with differences in reported
      contact to a speaker's voice and voice distinctiveness. Overall, the present
      study establishes a number of factors that account for substantial individual
      differences in personal voice identification.

PMID- 23168358
TI  - Eco-physiological response of two marine bivalves to acute exposition to
      commercial Bt-based pesticide.
AB  - Microbial products based on the entomopathogenic bacterium Bacillus thuringiensis
      (Bt) are among the most common biopesticides used worldwide to suppress insect
      pests in forests, horticulture and agricultural crops. Some of the effects of
      commercial Bt have been recorded for terrestrial and freshwater non-target
      organisms but little research is available on marine fauna. Nevertheless, due to
      the contiguity of agro-ecosystems and coastal habitats, marine fauna may be
      highly influenced by this control method. We studied the effect of a commercial
      Bt product on the physiological and ecological responses and the energy budget of
      two of the most frequent marine intertidal bivalves in the Mediterranean, the
      native Mytilaster minimus and the invasive Brachidontes pharaonis. To test the
      effects experimentally, we simulated the worst scenarios possible using the
      average dose applied to fields and a hypothetical accumulation dose. The results
      showed the feeding rates of both species were affected detrimentally by the
      different experimental conditions; higher concentrations led to higher
      respiration rates, however neither species showed any significant difference in
      excretion rates. The biopesticide had a significant effect on the energy budget,
      the values decreasing with doses. In addition, it led to high mortality for the
      worst treatments and, in both species, induced significantly higher cardiac
      activity than in the controls. These results indicate a measurable effect of Bt
      commercial products on marine organisms, and great attention should be paid to
      biopesticides composed by entomopathogenic bacteria and addictive compounds. In
      addition, the results highlight the urgent need to study not only the effects of
      anthropogenic pressures on target organisms but also to extend our view to other
      ecosystems not expected to be influenced. Gaining data at the organismal level
      should help increase the sustainability of pest control and reduce the
      consequences of side-effects.

PMID- 23168359
TI  - Psychological interventions in the rehabilitation of patients with chronic low
      back pain:  evidence and recommendations from systematic reviews and guidelines.
AB  - The purpose of the article is to summarize evidence and recommendations for
      psychological interventions in the rehabilitation of patients with chronic low
      back pain. We carried out a systematic literature search in several databases and
      on the websites of professional associations to identify relevant reviews and
      guidelines. In addition to the electronic search, a handsearch was carried out.
      Eligible publications were selected. We extracted and summarized both evidence
      for psychological interventions and recommendations on psychological diagnostics
      and interventions. Six systematic reviews and 14 guidelines were included. We
      collected recommendations and partially restricted evidence on the following
      psychological interventions: behavioural therapy, fear-avoidance training, stress
      management, relaxation therapy, patient education and back school. Most available
      evidence for psychological interventions in the rehabilitation of patients with
      chronic low back pain is of moderate to low quality. In addition, some of the
      older evidence is inapplicable to modern interventions using a biopsychosocial
      approach. Thus, high quality and current evidence is needed. The summary of
      guidelines shows that multimodal, multidisciplinary programmes including
      psychological interventions have become standard in the rehabilitation of
      patients with chronic low back pain. In most guidelines, however, there are no
      recommendations on which (psychological) intervention should be considered for
      which specific problem (problem-treatment pairs). Suggestions for future research
      and future guidelines are made.

PMID- 23168360
TI  - Decision making in non-AIDS-defining malignancies.

PMID- 23168361
TI  - Which treatment for high-risk patients with DLBCL?

PMID- 23168362
TI  - Bevacizumab plus oxaliplatin-based chemotherapy as adjuvant treatment for colon
      cancer (AVANT): a phase 3 randomised controlled trial.
AB  - BACKGROUND: Bevacizumab improves the efficacy of oxaliplatin-based chemotherapy
      in metastatic colorectal cancer. Our aim was to assess the use of bevacizumab in
      combination with oxaliplatin-based chemotherapy in the adjuvant treatment of
      patients with resected stage III or high-risk stage II colon carcinoma. METHODS:
      Patients from 330 centres in 34 countries were enrolled into this phase 3, open
      label randomised trial. Patients with curatively resected stage III or high-risk
      stage II colon carcinoma were randomly assigned (1:1:1) to receive FOLFOX4
      (oxaliplatin 85 mg/m(2), leucovorin 200 mg/m(2), and fluorouracil 400 mg/m(2)
      bolus plus 600 mg/m(2) 22-h continuous infusion on day 1; leucovorin 200 mg/m(2)
      plus fluorouracil 400 mg/m(2) bolus plus 600 mg/m(2) 22-h continuous infusion on
      day 2) every 2 weeks for 12 cycles; bevacizumab 5 mg/kg plus FOLFOX4 (every 2
      weeks for 12 cycles) followed by bevacizumab monotherapy 7.5 mg/kg every 3 weeks
      (eight cycles over 24 weeks); or bevacizumab 7.5 mg/kg plus XELOX (oxaliplatin
      130 mg/m(2) on day 1 every 2 weeks plus oral capecitabine 1000 mg/m(2) twice
      daily on days 1-15) every 3 weeks for eight cycles followed by bevacizumab
      monotherapy 7.5 mg/kg every 3 weeks (eight cycles over 24 weeks). Block
      randomisation was done with a central interactive computerised system, stratified
      by geographic region and disease stage. Surgery with curative intent occurred 4-8
      weeks before randomisation. The primary endpoint was disease-free survival,
      analysed for all randomised patients with stage III disease. This study is
      registered with ClinicalTrials.gov, number NCT00112918. FINDINGS: Of the total
      intention-to-treat population (n=3451), 2867 patients had stage III disease, of
      whom 955 were randomly assigned to receive FOLFOX4, 960 to receive bevacizumab
      FOLFOX4, and 952 to receive bevacizumab-XELOX. After a median follow-up of 48
      months (range 0-66 months), 237 patients (25%) in the FOLFOX4 group, 280 (29%) in
      the bevacizumab-FOLFOX4 group, and 253 (27%) in the bevacizumab-XELOX group had
      relapsed, developed a new colon cancer, or died. The disease-free survival hazard
      ratio for bevacizumab-FOLFOX4 versus FOLFOX4 was 1.17 (95% CI 0.98-1.39; p=0.07),
      and for bevacizumab-XELOX versus FOLFOX4 was 1.07 (0.90-1.28; p=0.44). After a
      minimum follow-up of 60 months, the overall survival hazard ratio for bevacizumab
      FOLFOX4 versus FOLFOX4 was 1.27 (1.03-1.57; p=0.02), and for bevacizumab-XELOX
      versus FOLFOX4 was 1.15 (0.93-1.42; p=0.21). The 573 patients with high-risk
      stage II cancer were included in the safety analysis. The most common grade 3-5
      adverse events were neutropenia (FOLFOX4: 477 [42%] of 1126 patients, bevacizumab
      FOLFOX4: 416 [36%] of 1145 patients, and bevacizumab-XELOX: 74 [7%] of 1135
      patients), diarrhoea (110 [10%], 135 [12%], and 181 [16%], respectively), and
      hypertension (12 [1%], 122 [11%], and 116 [10%], respectively). Serious adverse
      events were more common in the bevacizumab groups (bevacizumab-FOLFOX4: 297
      [26%]; bevacizumab-XELOX: 284 [25%]) than in the FOLFOX4 group (226 [20%]).
      Treatment-related deaths were reported in one patient receiving FOLFOX4, two
      receiving bevacizumab-FOLFOX4, and five receiving bevacizumab-XELOX.
      INTERPRETATION: Bevacizumab does not prolong disease-free survival when added to
      adjuvant chemotherapy in resected stage III colon cancer. Overall survival data
      suggest a potential detrimental effect with bevacizumab plus oxaliplatin-based
      adjuvant therapy in these patients. On the basis of these and other data, we do
      not recommend the use of bevacizumab in the adjuvant treatment of patients with
      curatively resected stage III colon cancer. FUNDING: Genentech, Roche, and
      Chugai.

PMID- 23168363
TI  - VEGF inhibition beyond tumour progression.

PMID- 23168364
TI  - Adjuvant bevacizumab in colon cancer: where did we go wrong?

PMID- 23168365
TI  - Obama: health-care reform, part two.

PMID- 23168368
TI  - The effect of acute fluid consumption and hydration status on percent body fat
      and minimum wrestling weight.
AB  - The weight certification program for wrestling requires a urine-specific gravity
      (USG) <1.020. However, the effect of acute rehydration on percent body fat (%BF)
      and minimum wrestling weight (MWW) is largely unknown. We examined the effect of
      acute fluid consumption on %BF and MWW. Twenty-five male subjects (18-22 years)
      were tested in a dehydrated state (USG > 1.020; DEH), 1 hour after rehydration
      (USG < 1.020; REH), and on a separate day in a hydrated state (USG < 1.020; HYD)
      which served as the criterion. Percent body fat was determined using skinfolds
      (SF), air displacement plethysmography (ADP), leg-to-leg bioelectrical impedance
      analysis (LBIA), and multifrequency bioelectrical impedance analysis (MBIA).
      Regardless of hydration state, %BF values were not significantly different when
      using SF (DEH = 13.35 +/- 4.03%; REH = 13.41 +/- 3.99%; HYD = 13.47 +/- 4.31%; p
      = 0.693) or ADP (DEH = 15.68 +/- 4.69%; REH = 16.19 +/- 4.57%; HYD = 15.88 +/-
      4.72%; p = 0.145). The MWW after fluid consumption (REH) was similar to the
      criterion (HYD) when using SF (REH = 72.04 +/- 8.25 kg; HYD = 72.23 +/- 8.15 kg;
      p = 1.000) and ADP (REH = 70.38 +/- 8.93 kg; HYD = 70.81 +/- 8.50 kg; p = 0.177)
      methods. Conversely, hydration state had a significant impact on LBIA (p = 0.011)
      and MBIA (p < 0.001) %BF values resulting in reduced MWWs. When using the SF and
      ADP methods to assess %BF, modest amounts of water (~1 L) restored euhydration
      (<1.020) without negatively affecting %BF or MWW. Therefore, acute fluid
      consumption (~1 L) may offer a safe alternative in which the weight certification
      program can be expedited.

PMID- 23168369
TI  - Relationships between asymmetries in functional movements and the star excursion
      balance test.
AB  - Lower-extremity functional asymmetries (LEFAs) have been shown to be related to
      performance and injury risk. However, consistency of expression between tasks is
      not well understood. The goal of this investigation was to examine relationships
      in vertical ground reaction force LEFA during standing, bodyweight squats,
      countermovement jumps (CMJs), and single-leg drop landings along with those
      produced in the Star Excursion Balance Test (SEBT). Twenty (9 men, 11 women)
      healthy, recreationally active young adults (mean +/- SD age: 21.9 +/- 2.6 years;
      height: 171 +/- 8.8 cm; mass: 67.2 +/- 1.9 kg) performed all tests in a single
      visit. Correlations of asymmetries between tasks as a whole group and in subsets
      with larger levels of asymmetries in each task were examined. Many significant
      correlations (p < 0.05) were found in the asymmetries between the functional
      tasks, between the reach directions of the SEBT, and between the functional tasks
      and the SEBT, though they were of low to moderate strength (|r| < 0.8) in the
      whole group. Except for standing, correlations typically improved in the subset
      analyses. Most noteworthy was the CMJ subset, which demonstrated strong
      relationships (|r| > 0.8) with asymmetries in the squat and with the SEBT.
      Correlations between reach directions in the SEBT improved in the subset
      comparisons but would not be considered strong. The results suggest that
      asymmetries are more likely to be expressed in multiple tasks as the bilateral
      difference increases, that intensity of effort plays a key role in the expression
      of asymmetries during bilateral tasks, tasks most relevant to the sport should be
      used when assessing athletes, and though not replacing functional tasks, the SEBT
      may serve an important role in the diagnosis of LEFA.

PMID- 23168370
TI  - Does an abdominal strengthening program influence leg stiffness during hopping
      tasks?
AB  - According to the spring mass model, leg stiffness (characterized by the measure
      of kleg) behavior is theoretically dependent on lower limb joint and trunk
      stiffness. Yet, the influence of the trunk as a possible regulator of kleg is
      unknown. This study investigated the influence of abdominal training on kleg
      during hopping tasks. Fourteen young male (age 18.5 +/- 0.5 years, height 176.4
      +/- 4.3 cm, weight 69.9 +/- 5.5 kg) soccer players (national level) participated
      in the study. Two groups (bracing B group, n = 7 vs. hollowing transversus
      abdominis [TrA] H group, n = 7) with identical training load followed an 8-week
      training program for abdominal strengthening. Contact time, flight time, jump
      height, and kleg were measured with an OptoJump system during a standardized
      hopping task (2.2 Hz) before and after the training program. Results for each
      group showed that only the H group increased kleg after the intervention (+15.7%)
      compared with the B group (+5.9%). This difference was explained by a 6.5%
      decrease in contact time in H group (-2.4% in B) with increased flight time
      (+8.8% in H vs. +2% in B). A large increase was found for jump height in H
      (+16.9%) compared with B group (+4.4%). This study showed that TrA strengthening
      improves leg stiffness in hopping tasks. Our findings suggest the potential role
      of abdominal muscles in controlling "lumbopelvic" stiffness as a part of the
      spring according to the spring mass model, and thus influencing kleg by reduced
      ground contact phase.

PMID- 23168367
TI  - Conventional chemotherapy (CHOEP-14) with rituximab or high-dose chemotherapy
      (MegaCHOEP) with rituximab for young, high-risk patients with aggressive B-cell
      lymphoma: an open-label, randomised, phase 3 trial (DSHNHL 2002-1).
AB  - BACKGROUND: High-dose therapy (HDT) followed by transplantation of autologous
      haemopoietic stem cells is frequently done as part of first-line therapy in young
      patients with high-risk aggressive B-cell lymphoma. We investigated whether HDT
      with cytotoxic agents identical to those used for conventional therapy followed
      by autologous stem-cell transplantation (ASCT) improved survival outcome compared
      with conventional chemotherapy when rituximab was added to both modalities.
      METHODS: We did an open-label, randomised trial comparing conventional
      chemotherapy (cyclophosphamide, doxorubicin, vincristine, etoposide, prednisone)
      and rituximab (R-CHOEP-14) with dose-escalated sequential HDT and rituximab (R
      MegaCHOEP) followed by repetitive ASCT in high-risk (age-adjusted International
      Prognostic Index [IPI] 2 or 3) patients aged 18-60 years with aggressive B-cell
      lymphoma. Eligible patients received radiotherapy for bulky, extranodal disease,
      or both. Randomisation (1:1) used the Pocock minimisation algorithm; patients
      were stratified by age-adjusted IPI factors, bulky disease, and centre. The
      primary endpoint was event-free survival. All analyses were done on the intention
      to-treat population. This trial is registered with ClinicalTrials.gov, number
      NCT00129090. FINDINGS: 136 patients were randomly assigned to R-CHOEP-14 and 139
      to R-MegaCHOEP. 130 patients in the R-CHOEP-14 group and 132 in the R-MegaCHOEP
      group were included in the intention-to-treat population. After a median of 42
      months (IQR 29-59), 3-year event-free survival was 69.5% (95% CI 61.3-77.7) in
      the R-CHOEP-14 group and 61.4% (52.8-70.0) in the R-MegaCHOEP group (p=0.14;
      hazard ratio 1.3, 95% CI 0.9-2.0). All 128 evaluable patients treated with R
      MegaCHOEP had grade 4 leucopenia, as did 48 (58.5%) of 82 patients with
      documented blood counts in the R-CHOEP-14 group. All 128 evaluable patients in
      the R-MegaCHOEP group had grade 3-4 thrombocytopenia, as did 26 (33.8%) of 77
      patients in the R-CHOEP-14 group with documented blood counts. The most important
      non-haematological grade 3 or 4 adverse event was infection, which occurred in 96
      (75.0%) of 128 patients treated with R-MegaCHOEP and in 40 (31.3%) of 128
      patients treated with R-CHOEP-14. INTERPRETATION: In young patients with high
      risk aggressive B-cell lymphoma, R-MegaCHOEP was not superior to conventional R
      CHOEP therapy and was associated with significantly more toxic effects. R-CHOEP
      14 with or without radiotherapy remains a treatment option for these patients,
      with encouraging efficacy. FUNDING: Deutsche Krebshilfe.

PMID- 23168371
TI  - Effects of different resistance training frequencies on the muscle strength and
      functional performance of active women older than 60 years.
AB  - Training frequency is an important resistance training variable, but its relative
      contribution to strength and functional performance (FP) gains in senior
      populations is not yet well defined. The present study investigated the effect of
      different resistance training frequencies on the strength and FP in active women
      aged 60 years and older. A total of 48 women (60-78 years) underwent a 16-week
      training program for 1 set of 10 repetition maximums (10RMs) of each exercise,
      being assigned in groups that performed training frequencies of 1, 2, or 3 days
      per week (EG1, EG2, and EG3) and a control group. Strength and FP tests were
      applied before and after the training protocol. All EGs, but not the control
      group, exhibited 10RM increases (bench press, seated dumbbell curl, knee
      extension, standing calf raise, p < 0.01). The 10RM increase for seated dumbbell
      curl and knee extension was always greater in the higher frequencies (p < 0.05).
      Timed up and go test improved equally in all EGs (p < 0.01). Chair sit-and-stand
      improvements in EG3 (-15.7%) and EG2 (-9.8%) were greater than in EG1 (-4.6%) (p
      < 0.01). Gait-speed improvement in EG3 (-11.6%) was greater than in EG2 (-5.1%)
      and EG1 (-3.9%) (p < 0.01). In conclusion, a higher weekly training frequency
      increased FP and strength to a greater extent than lower frequencies in active
      senior women.

PMID- 23168366
TI  - Continuation of bevacizumab after first progression in metastatic colorectal
      cancer (ML18147): a randomised phase 3 trial.
AB  - BACKGROUND: Bevacizumab plus fluoropyrimidine-based chemotherapy is standard
      treatment for first-line and bevacizumab-naive second-line metastatic colorectal
      cancer. We assessed continued use of bevacizumab plus standard second-line
      chemotherapy in patients with metastatic colorectal cancer progressing after
      standard first-line bevacizumab-based treatment. METHODS: In an open-label, phase
      3 study in 220 centres in Austria, Belgium, Czech Republic, Denmark, Estonia,
      Finland, France, Germany, the Netherlands, Norway, Portugal, Saudi Arabia, Spain,
      Sweden, and Switzerland, patients (aged >=18 years) with unresectable,
      histologically confirmed metastatic colorectal cancer progressing up to 3 months
      after discontinuing first-line bevacizumab plus chemotherapy were randomly
      assigned in a 1:1 ratio to second-line chemotherapy with or without bevacizumab
      2.5 mg/kg per week equivalent (either 5 mg/kg every 2 weeks or 7.5 mg/kg every 3
      weeks, intravenously). The choice between oxaliplatin-based or irinotecan-based
      second-line chemotherapy depended on the first-line regimen (switch of
      chemotherapy). A combination of a permuted block design and the Pocock and Simon
      minimisation algorithm was used for the randomisation. The primary endpoint was
      overall survival, analysed by intention to treat. This trial is registered with
      ClinicalTrials.gov, number NCT00700102. FINDINGS: Between Feb 1, 2006, and June
      9, 2010, 409 (50%) patients were assigned to bevacizumab plus chemotherapy and
      411 (50%) to chemotherapy alone. Median follow-up was 11.1 months (IQR 6.4-15.6)
      in the bevacizumab plus chemotherapy group and 9.6 months (5.4-13.9) in the
      chemotherapy alone group. Median overall survival was 11.2 months (95% CI 10.4
      12.2) for bevacizumab plus chemotherapy and 9.8 months (8.9-10.7) for
      chemotherapy alone (hazard ratio 0.81, 95% CI 0.69-0.94; unstratified log-rank
      test p=0.0062). Grade 3-5 bleeding or haemorrhage (eight [2%] vs one [<1%]),
      gastrointestinal perforation (seven [2%] vs three [<1%]), and venous
      thromboembolisms (19 [5%] vs 12 [3%]) were more common in the bevacizumab plus
      chemotherapy group than in the chemotherapy alone group. The most frequently
      reported grade 3-5 adverse events were neutropenia (65 [16%] in the bevacizumab
      and chemotherapy group vs 52 [13%] in the chemotherapy alone group), diarrhoea
      (40 [10%] vs 34 [8%], respectively), and asthenia (23 [6%] vs 17 [4%],
      respectively). Treatment-related deaths were reported for four patients in the
      bevacizumab plus chemotherapy group and three in the chemotherapy alone group.
      INTERPRETATION: Maintenance of VEGF inhibition with bevacizumab plus standard
      second-line chemotherapy beyond disease progression has clinical benefits in
      patients with metastatic colorectal cancer. This approach is also being
      investigated in other tumour types, including metastatic breast and non-small
      cell lung cancers. FUNDING: F Hoffmann-La Roche.

PMID- 23168372
TI  - Hemodynamic responses to resistance exercise with restricted blood flow in young
      and older men.
AB  - Exercise with blood flow restriction promotes significant improvements, and it
      has been considered an attractive exercise strategy, especially for older
      individuals. However, the acute cardiovascular responses to resistance exercise
      with blood flow restriction (BFR) are not fully known. The purpose of this study
      was to evaluate the hemodynamic responses during resistance exercise with BFR in
      young and older individuals. We compared hemodynamic responses in 15 young (30 +/
      3 years) and 12 older (66 +/- 7 years) subjects during low-intensity resistance
      biceps curl exercise with (BFR-RE) or without (RE) BFR in a random and crossover
      design. Heart rate (HR), mean blood pressure (MBP), calf blood flow (CBF), and
      calf vascular resistance (CVR) were evaluated. Both groups presented similar
      values at baseline. Compared with RE, HR and MBP were higher during BFR-RE for
      both the groups, and these changes were maintained during the recovery period. In
      both the groups, BFR-RE elicited larger decreases in CBF and increased CVR. Both
      groups showed a significant increase in double product during BFR-RE. In
      conclusion, resistance exercise with BFR elicits greater hemodynamic changes in
      healthy young and older subjects, with responses of similar magnitudes in both
      groups. The safety of BFR in clinical practice demands further study in
      vulnerable populations.

PMID- 23168373
TI  - The effect of high vs. low carbohydrate diets on distances covered in soccer.
AB  - The purpose of this study was to compare the distances covered during a 11-a-side
      soccer match after players had consumed either a high carbohydrate (CHO) or a low
      CHO diet. Twenty-two male professional soccer players formed 2 teams (A and B),
      of similar age, body characteristics, and training experience. The 2 teams played
      against each other twice with a week interval between. For 3.5 days before the
      first match, the players of team A followed a high CHO diet that provided 8 g CHO
      per kg body mass (BM) (HC), whereas team B players followed a low CHO diet that
      provided 3 g CHO per kg BM (LC) for the same time period. Before the second match
      the dietary treatment was reversed and followed for the same time period.
      Training during the study was controlled, and distances covered were measured
      using global positioning system technology. Every player covered a greater total
      distance in HC compared with the distance covered in LC (HC: 9,380 +/- 98 m vs.
      LC: 8,077 +/- 109 m; p < 0.01). All distances covered from easy jogging (7.15
      km.h-1) to sprinting (24.15 km.h-1) were also higher in HC compared with LC (p <
      0.01). When players followed the HC treatment, they won the match (team A vs.
      team B: 3-1 for the first game and 1-2 for the second game). The HC diet probably
      helped players to cover a greater distance compared with LC. Soccer players
      should avoid eating a low (3 g CHO per kg BM) CHO diet 3-4 days before an
      important soccer match and have a high CHO intake that provides at least 8 g CHO
      per kg BM.

PMID- 23168374
TI  - Analysis of sprinting activities of professional soccer players.
AB  - The aim of the study was a detailed analysis of the sprinting activity of
      professional soccer players. The study involved 147 players who played in 10
      matches of the 2008-09 and 2010-11 UEFA Europa League seasons. The number of
      performed sprints and total sprint distances covered by the players were examined
      using collected statistical material. Two types of sprints were distinguished
      based on their duration: S, short-duration sprint (below 5 seconds) and L, long
      duration sprint (above 5 seconds). Additionally, sprints were classified
      according to their distance: 0-10, 10.1-20.0, and >20 m, respectively. The
      analysis of the sprinting activity of soccer players also involved their
      respective positions of play. The study was carried out using Amisco Pro
      (version. 1.0.2), one of the most comprehensive up-to-date computer systems for
      match analysis. The statistical analysis revealed that the mean total sprint
      distance covered by players (>=24 km.h) amounted to 237 +/- 123 m. With regard to
      the position of play, the forwards covered the longest sprint distance (345 +/-
      129 m), that is, 9% longer than midfielders (313 +/- 119 m) and over 100% longer
      than central midfielders (167 +/- 87 m). The average number of sprints performed
      by the soccer players was 11.2 +/- 5.3. It should also be emphasized that about
      90% of sprints performed by professional soccer players were shorter than 5
      seconds, whereas only 10% were longer than 5 seconds. Analysis of physical loads
      of soccer players during matches can be useful for individualization of training
      of soccer players' speed capabilities. It is an essential instrument of modern
      planning and application of training loads.

PMID- 23168375
TI  - Evaluation of a specific reaction and action speed test for the soccer
      goalkeeper.
AB  - The aim of this study was to develop and evaluate a new test for the soccer
      goalkeeper that involved perceptual and movement response components (i.e.,
      sprint running, jumping, diving, and direction changing). The evaluation
      consisted of measurements in different age (U19 [18.0 +/- 0.9 years], n = 21; U14
      [14.1 +/- 0.3 years], n = 13) and performance (i.e., first goalkeepers and
      substitutes) groups of goalkeepers, including measures of test-retest
      reliability. Validity was assessed comparing the 2 groups of goalkeepers with
      different expertise levels (i.e., competitive level and age group). The test
      retest correlations of the reaction and action speed (RAS) test performance were
      significant in all single (intraclass correlation coefficient [ICC] = 0.68-0.95;
      p < 0.01) and complex measurements (ICC = 0.91; p < 0.01). The RAS single test
      performance was higher in older (U19) compared with in younger (U14) players (p <
      0.001), and they also showed better results in the RAS complex tests (p = 0.000),
      being significantly different between the first goalkeepers and their substitutes
      (p = 0.001). Moreover, for all age groups (i.e., U14, U19), defensive actions to
      the bottom corners were faster than those to the top corners, with large ES
      (i.e., > 1). The major findings of the study were that the RAS test provided a
      reliable and valid method of assessing specific defensive agility in a group of
      youth soccer goalkeepers. Performance responses during the RAS test allow coaches
      to discriminate between age-matched goalkeepers, identify weaknesses (e.g.,
      nonpreferred side dive performance), and to design specific training tasks.

PMID- 23168376
TI  - A skewed thiopurine metabolism is a common clinical phenomenon that can be
      successfully managed with a combination of low-dose azathioprine and allopurinol.
AB  - BACKGROUND AND AIMS: A skewed thiopurine metabolism is a phenomenon associated
      with both poor treatment response and toxicity. Our aim was to evaluate the
      frequency of this phenomenon and the relationship to thiopurine methyltransferase
      (TPMT) function. METHODS: All thiopurine metabolite measurements in adult
      patients (n=4033) between January 2006 and April 2012 were assessed to evaluate
      the occurrence of a skewed metabolism and the relationship to TPMT genotype and
      activity. RESULTS: A skewed metabolism was observed in 14% of all patients. It
      only developed in patients with a normal TPMT genotype, but was observed at all
      TPMT activity levels within the normal range (9.1-24.2 U/ml RBC). Two cases that
      illustrate typical clinical scenarios of a skewed metabolism and the effect of
      combination treatment with low-dose azathioprine and allopurinol are presented.
      CONCLUSIONS: A skewed metabolism is a common clinical phenomenon in patients with
      a normal TPMT function, which can develop at all TPMT activity levels within the
      normal range. We suggest that metabolite measurements should be considered in
      patients not responding to treatment and in those with hepatotoxicity or
      myelotoxicity in order to detect a skewed metabolism, since this phenomenon can
      be successfully managed by a combination of low-dose azathioprine and
      allopurinol.

PMID- 23168377
TI  - Mouse model of intraluminal MCAO: cerebral infarct evaluation by cresyl violet
      staining.
AB  - Stroke is the third cause of mortality and the leading cause of disability in the
      World. Ischemic stroke accounts for approximately 80% of all strokes. However,
      the thrombolytic tissue plasminogen activator (tPA) is the only treatment of
      acute ischemic stroke that exists. This led researchers to develop several
      ischemic stroke models in a variety of species. Two major types of rodent models
      have been developed: models of global cerebral ischemia or focal cerebral
      ischemia. To mimic ischemic stroke in patients, in whom approximately 80%
      thrombotic or embolic strokes occur in the territory of the middle cerebral
      artery (MCA), the intraluminal middle cerebral artery occlusion (MCAO) model is
      quite relevant for stroke studies. This model was first developed in rats by
      Koizumi et al. in 1986 (1). Because of the ease of genetic manipulation in mice,
      these models have also been developed in this species (2-3). Herein, we present
      the transient MCA occlusion procedure in C57/Bl6 mice. Previous studies have
      reported that physical properties of the occluder such as tip diameter, length,
      shape, and flexibility are critical for the reproducibility of the infarct volume
      (4). Herein, a commercial silicon coated monofilaments (Doccol Corporation) have
      been used. Another great advantage is that this monofilament reduces the risk to
      induce subarachnoid hemorrhages. Using the Zeiss stereo-microscope Stemi 2000,
      the silicon coated monofilament was introduced into the internal carotid artery
      (ICA) via a cut in the external carotid artery (ECA) until the monofilament
      occludes the base of the MCA. Blood flow was restored 1 hour later by removal of
      the monofilament to mimic the restoration of blood flow after lysis of a
      thromboembolic clot in humans. The extent of cerebral infarct may be evaluated
      first by a neurologic score and by the measurement of the infarct volume.
      Ischemic mice were thus analyzed for their neurologic score at different post
      reperfusion times. To evaluate the infarct volume, staining with 2,3,5
      triphenyltetrazolium chloride (TTC) was usually performed. Herein, we used cresyl
      violet staining since it offers the opportunity to test many critical markers by
      immunohistochemistry. In this video, we report the MCAO procedure; neurological
      scores and the evaluation of the infarct volume by cresyl violet staining.

PMID- 23168378
TI  - Quantitative and qualitative comparison of a new prosthetic suspension system
      with two existing suspension systems for lower limb amputees.
AB  - OBJECTIVE: The objectives of this study were to compare the effects of a newly
      designed magnetic suspension system with that of two existing suspension methods
      on pistoning inside the prosthetic socket and to compare satisfaction and
      perceived problems among transtibial amputees. DESIGN: In this prospective study,
      three lower limb prostheses with three different suspension systems were
      fabricated for ten transtibial amputees. The participants used each of the three
      prostheses for 1 mo in random order. Pistoning inside the prosthetic socket was
      measured by motion analysis system. The Prosthesis Evaluation Questionnaire was
      used to evaluate satisfaction and perceived problems with each suspension system.
      RESULTS: The lowest pistoning motion was found with the suction system compared
      with the other two suspension systems (P < 0.05). The new suspension system
      showed peak pistoning values similar to that of the pin lock system (P = 0.086).
      The results of the questionnaire survey revealed significantly higher
      satisfaction rates with the new system than with the other two systems in donning
      and doffing, walking, uneven walking, stair negotiation, and overall satisfaction
      (P < 0.05). CONCLUSIONS: The new suspension system has the potential to be used
      as an alternative to the available suspension systems. The pistoning motion was
      comparable to that of the other two systems. The new system showed compatible
      prosthetic suspension with the other two systems (suction and pin lock). The
      satisfaction with donning and doffing was high with the magnetic system.
      Moreover, the subjects reported fewer problems with the new system.

PMID- 23168379
TI  - Probes for narcotic receptor mediated phenomena. 46. N-substituted-2,3,4,9,10,10a
      hexahydro-1H-1,4a-(epiminoethano)phenanthren-6- and 8-ols - carbocyclic relatives
      of f-oxide-bridged phenylmorphans.
AB  - Oxide-bridged phenylmorphans were conceptualized as topologically distinct,
      structurally rigid ligands with 3-dimensional shapes that could not be
      appreciably modified on interaction with opioid receptors. An enantiomer of the N
      phenethyl-substituted ortho-f isomer was found to have high affinity for the MU
      receptor (K(i) = 7 nM) and was about four times more potent than naloxone as an
      antagonist. In order to examine the effect of introduction of a small amount of
      flexibility into these molecules, we have replaced the rigid 5-membered oxide
      ring with a more flexible 6-membered carbon ring. Synthesis of the new N
      phenethyl-substituted tricyclic N-substituted-2,3,4,9,10,10a-hexahydro-1H-1,4a
      (epiminoethano)phenanthren-6- and 8-ols resulted in a two carbon-bridged relative
      of the f-isomers, the dihydrofuran ring was replaced by a cyclohexene ring. The
      carbocyclic compounds had much higher affinity and greater selectivity for the MU
      receptor than the f-oxide-bridged phenylmorphans. They were also much more potent
      MU-antagonists, with activities comparable to naltrexone in the [(35)S]GTP-gamma
      S assay.

PMID- 23168381
TI  - The mechanical and strength properties of diamond.
AB  - Diamond is an exciting material with many outstanding properties; see, for
      example Field J E (ed) 1979 The Properties of Diamond (London: Academic) and
      Field J E (ed) 1992 The Properties of Natural and Synthetic Diamond (London:
      Academic). It is pre-eminent as a gemstone, an industrial tool and as a material
      for solid state research. Since natural diamonds grew deep below the Earth's
      surface before their ejection to mineable levels, they also contain valuable
      information for geologists. The key to many of diamond's properties is the
      rigidity of its structure which explains, for example, its exceptional hardness
      and its high thermal conductivity. Since 1953, it has been possible to grow
      synthetic diamond. Before then, it was effectively only possible to have natural
      diamond, with a small number of these found in the vicinity of meteorite impacts.
      Techniques are now available to grow gem quality synthetic diamonds greater than
      1 carat (0.2 g) using high temperatures and pressures (HTHP) similar to those
      found in nature. However, the costs are high, and the largest commercially
      available industrial diamonds are about 0.01 carat in weight or about 1 mm in
      linear dimension. The bulk of synthetic diamonds used industrially are 600 um or
      less. Over 75% of diamond used for industrial purposes today is synthetic
      material. In recent years, there have been two significant developments. The
      first is the production of composites based on diamond; these materials have a
      significantly greater toughness than diamond while still maintaining very high
      hardness and reasonable thermal conductivity. The second is the production at low
      pressures by metastable growth using chemical vapour deposition techniques.
      Deposition onto non-diamond substrates was first demonstrated by Spitsyn et al
      1981 J. Cryst. Growth 52 219-26 and confirmed by Matsumoto et al 1982 Japan J.
      Appl. Phys. 21 L183-5. These developments have added further to the versatility
      of diamond. Two other groups of materials based on carbon, namely the fullerenes
      and graphines have been identified in recent years and are now the subject of
      intense research.

PMID- 23168380
TI  - Initial evaluation of the antitumour activity of KGP94, a functionalized
      benzophenone thiosemicarbazone inhibitor of cathepsin L.
AB  - Kinetic analysis of the mode of inhibition of cathepsin L by KGP94, a lead
      compound from a privileged library of functionalized benzophenone
      thiosemicarbazone derivatives, demonstrated that it is a time-dependent,
      reversible, and competitive inhibitor of the enzyme. These results are consistent
      with the formation of a transient covalent bond, and are supported by molecular
      modeling that places the thiocarbonyl of the inhibitor in proximity to the
      thiolate moiety of the enzyme active site Cys25. KGP94 significantly decreased
      the activity of cathepsin L toward human type I collagen, and impeded both
      migration and invasion of MDA-MB-231 human breast cancer cells. Growth
      retardation was achieved in vivo against both recently implanted and established
      tumours using a C3H mouse mammary carcinoma model.

PMID- 23168382
TI  - Hippocampal and entorhinal cortex volume decline in cognitively intact elderly.
AB  - Studying the distribution and chronological sequence of brain morphological
      changes that occur in normal aging is crucial for understanding the mechanisms
      underlying these alterations and for distinguishing them from pathological
      processes. Whether the hippocampal formation is subjected to or spared from age
      related shrinkage still remains controversial. We used magnetic resonance imaging
      (MRI) in order to assess hippocampal and entorhinal morphology in two population
      based cognitively unimpaired cohorts (aged 53-55 years and 73-75 years,
      respectively) matched for gender, education, handedness, and apolipoprotein E
      status. Voxel-based morphometry (VBM-DARTEL) and shape analysis (FSL-FIRST)
      revealed significant bihemispheric age-related shrinkage of subiculum and cornu
      ammonis as well as of the entorhinal cortex (investigated with VBM only). The
      results lend further support to an effect of aging on medial temporal lobe
      morphology and thus may be of importance for the interpretation of structural
      imaging findings, especially in those diseases that are typically related to
      advancing age, as well as for the interpretation of functional imaging studies,
      where age-related differences in hippocampal activation may--to a locally varying
      degree--be explained by morphometric alterations.

PMID- 23168383
TI  - Heart extracellular matrix supports cardiomyocyte differentiation of mouse
      embryonic stem cells.
AB  - We have evaluated the effect of heart extracellular matrix (ECM) on the
      cardiomyocyte differentiation of mouse embryonic stem cells (ES cells) using de
      cellularized heart tissue. Several lines of evidence indicate that ECM plays
      significant roles in cell proliferation, cell death and differentiation, but role
      of ECM possessing a 3D structure in differentiation has not been studied in
      detail. We found that there are substantial differences in the quantitative
      protein profiles of ECM in SDS-treated heart tissue compared to that of liver
      tissue, as assessed by iTRAQTM quantitative proteomics analysis. When mouse ES
      cells were cultured on thin (60 MUm) sections of de-cellularized tissue, the
      expression of cardiac myosin heavy chain (cMHC) and cardiac troponin I (cTnI) was
      high in ES cells cultured on heart ECM compared with those cultured on liver ECM.
      In addition, the protein expression of cMHC and cTnI was detected in cells on
      heart ECM after 2 weeks, which was not detectable in cells on liver ECM. These
      results indicate that heart ECM plays a critical role in the cardiomyocyte
      differentiation of ES cells. We propose that tissue-specific ECM induced cell
      lineage specification through mechano-transduction mediated by the structure,
      elasticity and components of ECM.

PMID- 23168384
TI  - Characterization and antibacterial activity of amoxicillin-loaded electrospun
      nano-hydroxyapatite/poly(lactic-co-glycolic acid) composite nanofibers.
AB  - We report a facile approach to fabricating electrospun drug-loaded
      organic/inorganic hybrid nanofibrous system for antibacterial applications. In
      this study, nano-hydroxyapatite (n-HA) particles loaded with a model drug,
      amoxicillin (AMX) were dispersed into poly(lactic-co-glycolic acid) (PLGA)
      solution to form electrospun hybrid nanofibers. The loading of AMX onto n-HA
      surfaces (AMX/n-HA) and the formation of AMX/n-HA/PLGA composite nanofibers were
      characterized using different techniques. We show that AMX can be successfully
      adsorbed onto the n-HA surface and the formed AMX/n-HA/PLGA composite nanofibers
      have a uniform and smooth morphology with improved mechanical durability. Cell
      viability assay and cell morphology observation reveal that the formed AMX/n
      HA/PLGA composite nanofibers are cytocompatible. Importantly, the loaded AMX
      within the n-HA/PLGA hybrid nanofibers shows a sustained release profile and a
      non-compromised activity to inhibit the growth of a model bacterium,
      Staphylococcus aureus. With the significantly reduced burst-release profile, good
      cytocompatibility, improved mechanical durability, as well as the remained
      antibacterial activity, the developed AMX/n-HA/PLGA composite nanofibers should
      find various potential applications in the fields of tissue engineering and
      pharmaceutical science.

PMID- 23168385
TI  - Amphiphilic starlike dextran wrapped superparamagnetic iron oxide nanoparticle
      clsuters as effective magnetic resonance imaging probes.
AB  - Starlike polymers have been widely used in various fields, such as tissue
      engineering, imaging, gene and drug delivery because of their unique structures
      and properties. Dextran has long been used as a temporary plasma substitute
      because of its excellent biocompatibility. In this study, starlike polysaccharide
      with multiple dextran arms was designed and developed by attaching dextran to a
      beta-cyclodextrin core through click chemistry. Next, starlike dextran was
      modified with aliphatic chains and these amphiphilic polymers can self-assemble
      into nanoscale micelles in water, and their critical micelle concentration values
      (3.7 * 10(-8) M) are much lower comparing to its linear analogs (1.7 * 10(-7) M),
      resulting in more stable nanostructures in aqueous environment. These micelles
      can encapsulate multiple superparamagnetic iron oxide nanoparticles and forming
      clustering particle nanostructures in water, and the resulting nanocomposites
      have a high T(2) relaxivity of 436.8 Fe mm(-1) s(-1) under a 1.5T clinical
      magnetic resonance imaging (MRI) scanner. Further, dual functional probes were
      developed by loading both superparamagnetic iron oxide nanoparticles and small
      molecule anticancer drug doxorubicin into polymeric micelles. Multidrug-resistant
      breast cancer cells MCF-7/Adr treated with these probes can be characterized
      under MRI.

PMID- 23168386
TI  - A high energy-density tin anode for rechargeable magnesium-ion batteries.
AB  - A high energy-density Sn anode capable of displaying superior operating voltages
      and capacity, for rechargeable Mg-ion batteries, is highlighted. The intended
      application and performance of the anode is confirmed by coupling it with a
      Mo(6)S(8) cathode in a conventional battery electrolyte.

PMID- 23168387
TI  - Menin liver-specific hemizygous mice challenged with high fat diet show increased
      weight gain and markers of metabolic impairment.
AB  - OBJECTIVE: The menin tumor suppressor protein is abundantly expressed in the
      liver, although no function has been identified because of lack of tumor
      development in multiple endocrine neoplasia type 1 (Men1) null livers. We examine
      the phenotype of mice lacking one functional allele of Men1 (consistent with the
      phenotype in humans with MEN1 syndrome) challenged with high fat diet (HFD) to
      elucidate a metabolic function for hepatic menin. METHODS: In this study, we
      challenged mice harboring a liver-specific hemizygous deletion of Men1 (HETs)
      alongside wild-type (WT) counterparts with HFD for 3 months and monitored the
      severity of metabolic changes. We demonstrate that the HET mice challenged with
      HFD for 3 months show an increased weight gain with decreased glucose tolerance
      compared with WT counterparts. Along with these changes, there was a more severe
      serum hormone profile involving increased serum insulin, glucose and glucagon,
      all hallmarks of the type 2 diabetic phenotype. In concert with increased serum
      hormones, we found that these mice have significantly increased liver
      triglycerides coupled with increased liver steatosis and inflammatory markers.
      Quantitative real-time PCR and western blotting studies show increases in enzymes
      involved with lipogenesis and hepatic glucose production. CONCLUSION: We conclude
      that hepatic menin is required for regulation of diet-induced metabolism, and our
      studies indicate a protective role for the Men1 gene in the liver when challenged
      with HFD.

PMID- 23168388
TI  - Lumbar facet joint motion in patients with degenerative spondylolisthesis.
AB  - STUDY DESIGN: Controlled laboratory study. OBJECTIVE: To investigate the in vivo
      biomechanical effect of degenerative lumbar spondylolisthesis (DLS) on the motion
      of the facet joint during various functional weight-bearing activities. SUMMARY
      OF BACKGROUND DATA: Although the morphologic changes of the facet joints in
      patients with DLS have been reported in a few studies, no data have been reported
      on the kinematics of these facet joints. METHODS: Ten patients with DLS at L4-L5
      were studied. Each patient underwent a magnetic resonance imaging scan to obtain
      3-dimensional models of the lumbar vertebrae from L2-L5 and a dual fluoroscopic
      imaging scan in different postures: flexion-extension, left-right bending, and
      left-right torsion. The positions of the vertebrae were reproduced by matching
      the magnetic resonance imaging-based vertebral models to the fluoroscopic images.
      The kinematics of the facet joint and the ranges of motion were compared with
      those of healthy subjects and those of patients with degenerative disk diseases
      (DDD) previously published. RESULTS: In DLS patients, the range of rotation of
      the facet joints was significantly less at the DLS level (L4-L5) than that at the
      adjacent levels (L2-L3 and L3-L4), whereas the range of translation was similar
      at all levels. The range of rotation at the facet joints of the DLS level
      decreased compared with those of both the DDD patients and healthy subjects at
      the corresponding vertebral level (L4-L5), whereas no significant difference was
      found in the range of translation. The range of motion of facet joints in DLS and
      in DDD patients was similar at the adjacent levels (L2-L3 and L3-L4).
      CONCLUSIONS: The range of rotation decreased at the facet joints at the DLS level
      (L4-L5) in patients compared with those in healthy subjects and DDD patients.
      This decrease in range of rotation implies that the DLS disease may cause
      restabilization of the joint. The data may help the selection of conservative
      treatment or different surgical techniques for the DLS patients.

PMID- 23168389
TI  - Early follow-up outcomes of a new zero-profile implant used in anterior cervical
      discectomy and fusion.
AB  - STUDY DESIGN: Original article. OBJECTIVE: The purpose of this study is to
      analyze the primary efficacy and safety of a new zero-profile implant named Zero
      P in anterior cervical discectomy and fusion (ACDF) in Chinese population.
      SUMMARY OF BACKGROUND DATA: ACDF has become the preferred treatment for single
      level or multilevel cervical degenerative disk disease. Most surgeons prefer to
      place an anterior plate to ensure the stability and prevent subsequent graft
      related complications. However, the side effects of the anterior plate, such as
      soft tissue injury and dysphagia, are still unavoidable especially when
      multilevel fusion is observed with the patients. A new zero-profile interbody
      fusion device named Zero-P was developed. In China, the new device was first
      implemented by our department. METHODS: A total of 89 patients of cervical
      degenerative disk disease were enrolled in this study prospectively and treated
      by ACDF from June 2010 to November 2010. There were 39 patients with a mean age
      of 50.3 years (range, 30-65 y) who had Zero-P implanted in the target segment. A
      total of 71 Zero-Ps were implanted. Another 50 patients, with a mean age of 52.6
      (range, 38-70 y), had common cages implanted in the target segment with an
      anterior titanium plate. The mean follow-up time was 16.9 months, ranging from 12
      to 20 months. The clinical outcomes were evaluated using the Japanese Orthopaedic
      Association (JOA) score and the visual analog scale (VAS) score before and after
      operations. Incidence of dysphagia-related symptoms was recorded. A cervical Cobb
      angle was measured as the acute angle constructed by lines going along the back
      of C2 and C7 vertebral body on the standing lateral cervical x-ray. RESULTS: At 2
      , 6-, and 12-month follow-up, the JOA scores significantly increased and the VAS
      scores decreased correspondently compared with preoperational measurements in
      both groups. The cervical Cobb angle had a significant correction when compared
      with that before the operation. The incidence of dysphagia in the Zero-P group
      was lower compared with that in the cage with plate group, and the symptom
      duration was much shorter. CONCLUSIONS: The primary clinical and radiographic
      efficacies of Zero-P used in ACDF were satisfactory. The device could improve and
      maintain the cervical lordosis and disk height. The incidence of postoperative
      dysphagia was low. More patients and longer follow-up are demanded to confirm the
      results we have obtained in this study.

PMID- 23168390
TI  - 3D-FSE Isotropic MRI of the Lumbar Spine: Novel Application of an Existing
      Technology.
AB  - STUDY DESIGN: Retrospective diagnostic trial. OBJECTIVE: To determine the
      diagnostic performance of 3-dimensional isotropic fast/turbo spin-echo (3D-TSE)
      in routine lumbar spine magnetic resonance imaging (MRI). SUMMARY OF BACKGROUND
      DATA: Conventional 2-dimensional fast spin-echo (2D-FSE) MRI requires independent
      acquisition of each desired imaging plane. This is time consuming and potentially
      problematic in spine imaging, as the plane of interest varies along the vertical
      axis due to lordosis, kyphosis, or possible deformity. 3D-TSE provides the
      capability to acquire volumetric data sets that can be dynamically reformatted to
      create images in any desired plane. METHODS: Eighty subjects scheduled for
      routine lumbar MRI were included in a retrospective trial. Each subject underwent
      both 3D-TSE and conventional 2D-FSE axial and sagittal MRI sequences. For each
      subject, the 3D-TSE and 2D-FSE sequences were separately evaluated (minimum 4 wk
      apart) in a randomized order and read independently by 4 reviewers. Images were
      evaluated using specific criteria for stenosis, herniation, and degenerative
      changes. RESULTS: The intermethod reliability for the 4 reviewers was 85.3%.
      Modified intermethod reliability analysis, disregarding disagreements between the
      lowest 2 descriptors for appropriate criteria (equivalent to "none" and "mild"),
      revealed average overall agreement of 94.6%. Using the above, modified criteria,
      interobserver variability for 3D-TSE was 89.1% and 88.3% for 2D-FSE (P=0.05), and
      intraobserver variability for 3D-TSE was 87.2% and 82.0% for 2D-FSE (P<0.01). The
      intermethod agreement between 3D-TSE and 2D-FSE was statistically noninferior to
      intraobserver 2D-FSE variability (P<0.01). CONCLUSIONS: This systematic
      evaluation showed that there is a very high degree of agreement between
      diagnostic findings assessed on 3D-TSE and conventional 2D-FSE sequences.
      Overall, intermethod agreement was statistically noninferior to the intraobserver
      agreement between repeated 2D-FSE evaluations. Overall, this study shows that 3D
      TSE performs equivalently, if not superiorly to 2D-FSE sequences. Reviewers found
      particular utility for the ability to manipulate image planes with the 3D-TSE if
      there was greater pathology or anatomic variation.

PMID- 23168391
TI  - Asymmetric Facet Joint Osteoarthritis and Its Relationships to Facet Orientation,
      Facet Tropism, and Ligamentum Flavum Thickening.
AB  - STUDY DESIGN: The degrees of osteoarthritis of the left and right facet joints
      were evaluated by using computerized tomography among elderly patients with low
      back or leg pain. OBJECTIVE: To reveal the phenomenon of asymmetry regarding
      facet joint osteoarthritis (FJOA) in old patients and establish its relationships
      to spinal level, facet orientation, facet tropism and ligamentum flavum (LF)
      thickening. SUMMARY OF BACKGROUND DATA: There were few reports regarding left
      right asymmetry among severity of FJOA and its relationships to spinal level,
      facet orientation, facet tropism, and LF thickening remained unclear. METHODS:
      The grade of bilateral FJOA was evaluated using 4-grade scale on computerized
      tomography images at the L3-4, L4-5, and L5-S1 levels of patients with age
      ranging from 60 to 80 years. All subjects were divided into 2 groups: symmetric
      FJOA group (FJOA I-II on both sides or FJOA III-IV on both sides) and asymmetric
      FJOA group (FJOA I-II on one side and FJOA III-IV on the other side). The
      relationships of FJOA to spinal level, facet orientation, facet tropism, and LF
      hypertrophy were evaluated. RESULTS: No association between asymmetric FJOA and
      spinal level was noted (P>0.05). In asymmetric FJOA group, significant difference
      in facet orientation between 2 sides was observed at the L4-5 (P=0.018) and L5-S1
      levels (P=0.033). Compared with symmetric FJOA, asymmetric FJOA showed
      significant difference in prevalence of facet tropism at the L5-S1 level
      (P<0.001). The LF showed significantly thicker on the side of FJOA III-IV than
      the side of FJOA I-II at each level in asymmetric FJOA group (P<0.05). However,
      no difference was found in thickness between 2 sides in symmetric FJOA group
      (P>0.05). CONCLUSIONS: Asymmetric FJOA is associated with facet orientation and
      tropism, but not with spinal level. There is a close relationship between
      severity of FJOA and LF thickness.

PMID- 23168392
TI  - Hybrid Decompression and Fixation Technique Versus Plated 3-Vertebra Corpectomy
      for 4-Segment Cervical Myelopathy: Analysis of 81 Cases With a Minimum 2-Year
      Follow-Up.
AB  - STUDY DESIGN: A retrospective comparative study. OBJECTIVE: The purpose of this
      study was to compare the stability and outcomes of a hybrid technique with those
      of a 3-vertebra corpectomy in the management of 4-segment cervical myelopathy.
      SUMMARY OF BACKGROUND DATA: Patients with primarily ventral disease and loss of
      cervical lordosis are considered good candidates for anterior surgery. Cervical
      corpectomy is commonly performed in patients with multilevel cervical myelopathy.
      Corpectomies including >3 vertebraes entail an extremely high risk of
      reconstruction failure. To avoid the need to perform a 3-vertebra corpectomy, we
      use a hybrid decompression and fixation technique. This hybrid technique is a
      technique to obtain optimum decompression and fixation in patients with
      multilevel cervical myelopathy. METHODS: A total of 81 patients with multilevel
      cervical myelopathy who underwent 4-segment cervical fixation with a minimum 2
      year follow-up were included. RESULTS: The hybrid technique involved combining a
      plated 2-vertebra corpectomy and single-level discectomy with stand-alone cage
      fixation. This technique was performed in 39 patients, and the plated 3-vertebra
      corpectomy was performed in 42 patients. Nine patients (21%) who underwent the
      plated 3-vertebra corpectomy were treated with halo immobilization, but no
      patient in the hybrid group required this treatment (P=0.002). There were fewer
      instances of reconstruction failure in the hybrid group than in the 3-vertebra
      corpectomy group (0% vs. 10%, respectively; P=0.048) and fewer instances of C5
      palsy (3% vs. 17%, respectively; P <0.0001). The incidence of postoperative C5
      palsy was 25% for C3-C5 corpectomy, 19% for C4-C6 corpectomy, and 11% for C4-C5
      corpectomy+C6-C7 discectomy. CONCLUSIONS: The hybrid technique has the following
      advantages over 3-vertebra corpectomy for 4-segment cervical fixation: a shorter
      graft bone and plate are required; the fixed segment has greater initial
      stability; postoperative external immobilization is simplified; and the risk of
      reconstruction failure and postoperative C5 palsy is reduced markedly.

PMID- 23168393
TI  - Apical wiring technique in surgical treatment of adolescent idiopathic scoliosis:
      the intermediate outcomes between Lenke types.
AB  - STUDY DESIGN: Retrospective cohort study of apical wiring technique for surgical
      treatment of adolescent idiopathic scoliosis patients. OBJECTIVE: To evaluate the
      intermediate outcome of adolescent idiopathic scoliosis patients treated with
      apical wiring technique. SUMMARY OF BACKGROUND DATA: Regarding surgical treatment
      for adolescent idiopathic scoliosis, there are reports of the superiority of
      coronal plane correction using all-screw constructs compared with all-hook or
      hybrid constructs. Major limitations of all-screw constructs are thoracic
      hypokyphosis and increased proximal junctional kyphosis. There are few reports
      about apical wiring technique outcomes and no reports of this surgical technique
      comparing Lenke types. METHODS: Consecutive adolescent idiopathic scoliosis
      patients treated with apical wiring technique were analyzed. Inclusion criteria
      were patient 21 years old or younger, who underwent a posterior only surgical
      correction with a follow-up of at least 2 years. Radiographic data were analyzed
      according to the criteria given by Lenke and colleagues. The radiographic
      parameters included global balance, Cobb angle, curve flexibility, apical
      vertebral translation, tilt angle of lower instrumented vertebra, angle of caudal
      disk to the lower instrumented vertebra, thoracic kyphosis, lumbar lordosis, and
      proximal junctional angle preoperatively and postoperatively. RESULTS: There was
      a significant improvement of Cobb angle in every Lenke type with an average
      correction of 74.6%. At latest follow-up, the average loss of correction was 3.5%
      (1.9 degrees). The greatest loss of correction for the minor curve of Lenke 2 was
      14.1% (5.8 degrees). There was an improvement of thoracic kyphosis in
      hypokyphosis group (1.9-21.1 degrees; P<0.001) and hyperkyphosis group (49.8-33.2
      degrees; P=0.001). Thoracic normokyphosis alignment was also preserved. No cases
      of abnormal proximal junctional kyphosis were noted in this cohort. CONCLUSIONS:
      Apical wiring technique for surgical treatment of adolescent idiopathic scoliosis
      provides an average correction of 71.1% at 3.4 years of average follow-up with
      harmonious sagittal plane correction even with preexisting abnormal thoracic
      kyphosis.

PMID- 23168394
TI  - Thoracic myelopathy caused by ossification of the ligamentum flavum: a
      retrospective study in Chinese patients.
AB  - STUDY DESIGN: A retrospective clinical study of 19 cases of ossification of
      ligamentum flavum (OLF) in Chinese population. OBJECTIVE: To inspect the
      epidemiology, clinical presentation, pathology, radiologic findings, and
      treatment outcome in 19 Chinese patients of OLF at a single institution. SUMMARY
      OF BACKGROUND DATA: OLF in the thoracic region causing neurological impairment is
      a rare pathologic entity described mainly in Japanese literature. The present
      study represents a series of Chinese patients with OLF at the thoracic spine.
      METHODS: Nineteen patients (7 male and 12 female; ages ranging between 39 and 73
      y) were included in this study. All patients have been treated by posterior
      thoracic extensive decompressive laminectomy. Neurological status was evaluated
      using the Japanese Orthopedic Association (JOA) score, the recovery rate, and the
      Oswestry Disability Index (ODI) before and after surgery. Patients' pain relief
      was evaluated using a visual analog scale (VAS) pain score. RESULTS: Mean JOA
      score was 3.16+/-1.05 before surgery to 8.34+/-3.28 after surgery. Mean recovery
      rate was 61.4%+/-32.5%. Mean ODI scores had significantly decreased from 66.36%+/
      10.91% before surgery to 25.45%+/-12.19% after surgery. The result of VAS score
      were 6.29+/-1.83 before the operation and 2.18+/-1.90 at final follow-up. All
      patients improved at the end of the evaluation period. There was no recurrence.
      CONCLUSIONS: Early diagnosis and sufficient surgical treatment play key roles in
      improving functional outcomes. Posterior thoracic extensive decompressive
      laminectomy gives satisfactory results and leads to significant clinical
      improvement.

PMID- 23168395
TI  - Mid-term Outcomes of Anterior Cervical Fusion for Cervical Spondylosis With
      Sympathetic Symptoms.
AB  - STUDY DESIGN: Prospective study. OBJECTIVE: The purpose of this study is to
      elucidate mid-term outcomes of anterior cervical fusion for cervical spondylosis
      with sympathetic symptoms (CSSS). SUMMARY OF BACKGROUND DATE: The terminology,
      pathogenesis, diagnosis, and treatment of CSSS remain controversial. Surgical
      treatment of CSSS has been rarely reported. This is the first prospective study
      to evaluate the mid-term outcome of surgical treatment of CSSS. METHODS: Thirty
      one patients who were diagnosed with CSSS in 2006 were evaluated prospectively.
      All patients were assigned to undergo anterior cervical fusion with posterior
      longitudinal ligament (PLL) resection and followed up for >=5 years. Sympathetic
      symptoms such as vertigo, headache, and tinnitus, etc. were evaluated using the
      sympathetic symptom 20-point score. Neurological status was assessed using the
      Japanese Orthopedic Association (JOA) score. Clinical and radiologic data were
      prospectively collected before surgery, and at 1 week, 2 months, 6 months, 2
      years, and 5 years after surgery. Surgical complications and morbidities of other
      diseases during the follow-up were also recorded. RESULTS: The mean 20-point
      score decreased significantly from 7.3+/-3.5 before surgery to 2.2+/-2.7 at the
      final follow-up (P<0.001), giving a mean recovery rate of 66.1%+/-50.3%. Good to
      excellent results were attained in 80.6% of these patients. The sympathetic
      symptoms were relieved in 23 of the 31 patients in the early postoperative
      period, and 5 patients in 2 months. No relief of sympathetic symptoms was found
      in 3 patients. The mean JOA score improved significantly from 12.0+/-1.9 before
      surgery to 14.8+/-1.5 by the end of the follow-up (P<0.001). No late neurological
      deterioration was found in this group. CONCLUSIONS: The mid-term outcomes of
      anterior cervical fusion with PLL resection for CSSS have been satisfactory.
      Differential diagnosis before surgery is of great importance. PLL may play a role
      in presenting sympathetic symptoms.

PMID- 23168396
TI  - Two-Year Evaluation of the X-STOP Interspinous Spacer in Different Primary
      Patient Populations With Neurogenic Intermittent Claudication Because of Lumbar
      Spinal Stenosis.
AB  - STUDY DESIGN: Multicenter, prospective single-arm study in patients diagnosed
      with neurogenic intermittent claudication because of lumbar spinal stenosis.
      OBJECTIVE: To collect data from 2 different primary patient populations, new
      participants meeting entry criteria [Continued Access Program (CAP)], or subjects
      who had been randomly assigned to nonsurgical management in the pivotal
      Investigational Device Exemption study and failed to respond upon study
      completion [Crossover Study (COS)]. SUMMARY OF BACKGROUND DATA: The X-STOP
      interspinous spacer is a minimally invasive treatment option for neurogenic
      intermittent claudication shown to improve pain, physical functioning, and/or
      overall quality of life. METHODS: Fifty-five subjects were enrolled, 42 in CAP
      and 13 in COS. Zurich Claudication Questionnaire (ZCQ) success rates were
      obtained based on the number of subjects achieving a threshold level of success.
      Mean SF-36 domain scores were compared with baseline using repeated measures
      analysis of variance. RESULTS: Eighty percent of subjects completed the study. At
      2 years, 26/43 subjects (60.5%) achieved clinically significant improvement in
      the Symptom Severity domain, 25/43 (58.1%) achieved clinically significant
      improvement in the Physical Function domain, and 31/44 (70.5%) achieved
      clinically significant improvement in the Patient Satisfaction domain of the ZCQ.
      Statistically significant improvement in mean scores was obtained in all physical
      domains of the SF-36 (with the exception of General Health) at 24 months. Mean
      improvement in ZCQ and SF-36 scores was not as pronounced in the COS cohort
      compared with the CAP cohort. The most frequently reported device-related or
      treatment-related adverse event was stenosis pain reported by 3 subjects.
      CONCLUSIONS: Overall data are consistent with the randomized pivotal
      Investigational Device Exemption trial. On the basis of the COS cohort which was
      subject to several additional years of failed conservative treatment, overall
      success rates do not improve as greatly in patients with long-standing lumbar
      spinal stenosis symptoms.

PMID- 23168397
TI  - Single fracture in the atlas vertebral arch: analysis of an unusual event.
AB  - STUDY DESIGN: Retrospective study. OBJECTIVE: The aim of this study is to show
      that a single traumatic fracture of the atlas is unusual but not rare and
      requires specific management strategies, which can be highlighted by the study of
      the junctional ligaments and membranes. SUMMARY OF BACKGROUND DATA: A single
      traumatic fracture of the atlas arch is considered a rare event and has been
      analyzed in few case reports. Ligaments and membranes play a primary role in
      providing stability to the craniovertebral junction area. METHODS: Here, we
      report 10 cases of a single traumatic fracture of the atlas arch: 4 cases were
      part of our series of spine injuries and were studied by magnetic resonance
      imaging during the acute phase to assess the junctional ligaments. The remaining
      6 cases were obtained from the Literature. RESULTS: Indirect signs of a traumatic
      ligamentous injury were found only in 1 patient. However, in all cases, these
      fractures were considered biomechanically stable and all patients were discharged
      with a rigid collar. During the follow-up, all patients reported an improvement
      in their neck pain and tenderness, with radiologic signs of bone healing.
      CONCLUSIONS: A single fracture of the atlas arch is an unusual traumatic event
      that results from slow-force impact. Medical experience in treating this specific
      fracture subtype is nowadays poor because of the paucity of the literature; thus,
      this unusual condition may either be underestimated or even overstudied and
      overtreated. Nowadays, it seems reasonable to assume that the management should
      be conservative in all cases and that magnetic resonance imaging often plays only
      a marginal role.

PMID- 23168398
TI  - Identification of an atypical zinc metalloproteinase, ZmpC, from an epidemic
      conjunctivitis-causing strain of Streptococcus pneumoniae.
AB  - Streptococcus pneumoniae is a pathogen associated with a range of invasive and
      noninvasive infections. Despite the identification of the majority of virulence
      factors expressed by S. pneumoniae, knowledge of the strategies used by this
      bacterium to trigger infections, especially those originating at wet-surfaced
      epithelia, remains limited. In this regard, we recently reported a mechanism used
      by a nonencapsulated, epidemic conjunctivitis-causing strain of S. pneumoniae
      (strain SP168) to gain access into ocular surface epithelial cells.
      Mechanistically, strain SP168 secretes a zinc metalloproteinase, encoded by a
      truncated zmpC gene, to cleave off the ectodomain of a vital defense component -
      the membrane mucin MUC16 - from the apical glycocalyx barrier of ocular surface
      epithelial cells and, thereby invades underlying epithelial cells. Here, we
      compare the truncated SP168 ZmpC to its highly conserved archetype from S.
      pneumoniae serotype 4 (TIGR4), which has been linked to pneumococcal virulence in
      previous studies. Comparative nucleotide sequence analyses revealed that the zmpC
      gene corresponding to strain SP168 has two stretches of DNA deleted near its 5'
      end. A third 3 bp in-frame deletion, resulting in the elimination of an alanine
      residue, was found towards the middle segment of the SP168 zmpC. Closer
      examination of the primary structure revealed that the SP168 ZmpC lacks the
      canonical LPXTG motif - a signature typical of several surface proteins of gram
      positive bacteria and of other pneumococcal zinc metalloproteinases.
      Surprisingly, in vitro assays performed using recombinant forms of ZmpC indicated
      that the truncated SP168 ZmpC induces more cleavage of the MUC16 ectodomain than
      its TIGR4 counterpart. This feature may help explain, in part, why S. pneumoniae
      strain SP168 is better equipped at abrogating the MUC16 glycocalyx barrier en
      route to causing epidemic conjunctivitis.

PMID- 23168399
TI  - Impact of an exercise program on muscular and functional performance and plasma
      levels of interleukin 6 and soluble receptor tumor necrosis factor in prefrail
      community-dwelling older women: a randomized controlled trial.
AB  - OBJECTIVE: To examine the impact of a muscle resistance program (MRP) on muscular
      and functional performance and on interleukin 6 (IL-6) and soluble tumor necrosis
      factor receptor-1 (sTNFr1) plasma levels in prefrail community-dwelling women.
      DESIGN: Randomized controlled trial crossover design with a postintervention and
      short-term follow-up. SETTING: University hospital. PARTICIPANTS: Prefrail
      community-dwelling women (N=32; >=65y). INTERVENTION: The MRP was designed based
      on the exercise at 75% of each participant's maximum load (10wk, 3 times/wk).
      MAIN OUTCOME MEASURES: Plasma concentrations of IL-6 and sTNFr1 (high-sensitivity
      enzyme-linked immunosorbent assay kits), muscle strength of the knee extensors
      (isokinetic), and functional performance (Timed Up & Go [TUG] test and 10-meter
      walk test [10MWT]). RESULTS: There were significant differences in functional and
      muscular performance between the pre-MRP, post-MRP, and 10-week follow-up period.
      After the MRP, both functional (TUG, pre-MRP=11.1s vs post-MRP=10.4s, P=.00;
      10MWT, pre-MRP=4.9s vs post-MRP, 4.4s, P=.00) and muscular performances (pre
      MRP=77.8% and post-MRP=83.1%, P=.02) improved. After cessation of the MRP (follow
      up period), sTNFr1 plasma levels increased by 21.4% at 10-week follow-up (post
      MRP, 406.4pg/mL; 10-week follow-up, 517.0pg/mL; P=.03). There were significant
      differences in sTNFr1 (P=.01). CONCLUSIONS: The MRP was effective in improving
      functional and muscular performances, although alterations in plasma levels of IL
      6 and sTNFr1 could not be identified after the MRP. Cessation of the MRP after 10
      weeks resulted in increased plasma levels of sTNFr1.

PMID- 23168400
TI  - Impact of hydrophilic catheters on urinary tract infections in people with spinal
      cord injury: systematic review and meta-analysis of randomized controlled trials.
AB  - OBJECTIVES: To identify randomized controlled trials comparing the use of
      hydrophilic and nonhydrophilic catheters for intermittent catheterization (IC) in
      patients with spinal cord injury (SCI), and to perform a meta-analysis evaluating
      the occurrence of hematuria and urinary tract infection (UTI). DATA SOURCES: We
      searched the following electronic databases to identify studies: EMBASE (1991 to
      August 2011), PubMed (1991 to August 2011), Cochrane Library (no date
      restriction), China National Knowledge Infrastructure (no date restriction), and
      the Chinese Biomedical Literature Database (no date restriction). STUDY
      SELECTION: Randomized controlled trials, parallel-control, crossover-control, and
      prospective cohort studies that assessed morbidity associated with the use of
      hydrophilic catheters and nonhydrophilic catheters in patients after SCI were
      included. DATA EXTRACTION: Data extraction was performed using standardized forms
      of the Cochrane Collaboration. Methodologic quality was independently assessed by
      2 reviewers using the Downs and Black instrument. Pooled odds ratios (ORs) with
      95% confidence intervals (CIs) were calculated for dichotomous data. DATA
      SYNTHESIS: Five studies involving 508 subjects; 462 subjects completed the study
      and were included in this meta-analysis. There was a significantly lower
      incidence (OR=.36; 95% CI, 24%-54%; P<.0001) of reported UTIs in the hydrophilic
      treated group compared with the nonhydrophilic-treated group. Hematuria was also
      reported significantly less in the hydrophilic catheter group than in the
      nonhydrophilic catheter group (OR=.57; 95% CI, 35%-92%; P=.001). CONCLUSIONS:
      This meta-analysis found UTIs and hematuria less frequently associated with the
      use of hydrophilic-coated catheters for IC in patients with SCI. These findings
      support the use of hydrophilic catheters in this patient population.

PMID- 23168401
TI  - Reducing robotic guidance during robot-assisted gait training improves gait
      function: a case report on a stroke survivor.
AB  - OBJECTIVE: To test the feasibility of patient-cooperative robotic gait training
      for improving locomotor function of a chronic stroke survivor with severe lower
      extremity motor impairments. DESIGN: Single-subject crossover design. SETTING:
      Performed in a controlled laboratory setting. PARTICIPANT: A 62-year-old man with
      right temporal lobe ischemic stroke was recruited for this study. The baseline
      lower-extremity Fugl-Meyer score of the subject was 10 on a scale of 34, which
      represented severe impairment in the paretic leg. However, the subject had a good
      ambulation level (community walker with the aid of a stick cane and ankle-foot
      orthosis) and showed no signs of sensory or cognitive impairments. INTERVENTIONS:
      The subject underwent 12 sessions (3 times per week for 4wk) of conventional
      robotic training with the Lokomat, where the robot provided full assistance to
      leg movements while walking, followed by 12 sessions (3 times per week for 4wk)
      of patient-cooperative robotic control training, where the robot provided minimal
      guidance to leg movements during walking. MAIN OUTCOME MEASURES: Clinical
      outcomes were evaluated before the start of the intervention, immediately after 4
      weeks of conventional robotic training, and immediately after 4 weeks of
      cooperative control robotic training. These included: (1) self-selected and fast
      walking speed, (2) 6-minute walk test, (3) Timed Up & Go test, and (4) lower
      extremity Fugl-Meyer score. RESULTS: Results showed that clinical outcomes
      changed minimally after full guidance robotic training, but improved considerably
      after 4 weeks of reduced guidance robotic training. CONCLUSIONS: The findings
      from this case study suggest that cooperative control robotic training is
      superior to conventional robotic training and is a feasible option to restoring
      locomotor function in ambulatory stroke survivors with severe motor impairments.
      A larger trial is needed to verify the efficacy of this advanced robotic control
      strategy in facilitating gait recovery after stroke.

PMID- 23168402
TI  - Isolation and characterization of NAI-802, a new lantibiotic produced by two
      different Actinoplanes strains.
AB  - Lantibiotics are biologically active peptides produced by Gram-positive bacteria.
      Starting from fermentation broth extracts preselected from a high-throughput
      screening program for discovering cell-wall inhibitors, we successfully isolated
      a new lantibiotic produced by Actinoplanes sp., designated as NAI-802. MS and NMR
      analysis together with explorative chemistry established that NAI-802 consists of
      21 amino acids, 19 of which are identical to those present in the class II
      lantibiotic actagardine. Interestingly, NAI-802 carries one extra alanine and one
      extra arginine at the N- and C-termini, respectively. As expected from the
      overall higher positive charge, NAI-802 was slightly more active than actagardine
      against staphylococci and streptococci. Further improvement of its antibacterial
      activity was achieved by adding one additional positive charge through conversion
      of the C-terminal carboxylate into the corresponding basic amide. NAI-802 thus
      represents a novel promising candidate for treating Gram-positive infections
      caused by multidrug-resistant pathogens.

PMID- 23168403
TI  - Susceptibility of different phases of biofilm of Klebsiella pneumoniae to three
      different antibiotics.
AB  - The existence of majority of bacteria in biofilm mode makes it difficult to
      eradicate them as antibiotics at much higher concentrations than the MICs are
      required to destroy these bacteria. This study investigated the effect of
      different classes of antibiotics on different phases of biofilm formed by
      Klebsiella pneumoniae. The organism was grown in different phases relevant to
      biofilm formation: planktonic cells at mid-log phase, planktonic cells at
      stationary phase, adherent monolayers and mature biofilms and their
      susceptibility to different classes of antibiotics was assessed. The results
      showed that planktonic organisms were susceptible to ciprofloxacin, amikacin and
      piperacillin, and their MBC values were same or eight times higher than their
      corresponding MICs. MBC of ciprofloxacin and amikacin was found to be four and
      eight times higher for monolayer than planktonic cells. On the other hand, MBC of
      piperacillin was >1024 MUg ml(-1). K. pneumoniae in a biofilm growth mode was
      more resistant to antibiotics than all other modes. The effect of amikacin and
      ciprofloxacin on young and older biofilms, at the highest achievable serum
      concentrations, was also examined. It was observed that amikacin at a
      concentration of 40 MUg ml(-1) was able to eradicate the young biofilms; however,
      with increase in the age of the biofilm, it became completely ineffective.
      Calcofluor staining suggested increased production of exopolysaccharide in older
      biofilm compared with younger biofim that might be responsible for the increased
      resistance of older biofilm of K. pneumoniae to antibiotics.

PMID- 23168404
TI  - A new ascochlorin derivative from Cylindrocarpon sp. FKI-4602.
AB  - Cylindrol A5, a new ascochlorin congener, was isolated along with 14 known
      compounds from the culture broth of Cylindrocarpon sp. FKI-4602 by solvent
      extraction, octadecylsilane column chromatography and HPLC. The structure of
      cylindrol A5 was elucidated by spectral analyses, including NMR. The compound has
      an ascochlorin skeleton consisting of a resorcin aldehyde and a cyclohexanone
      moieties. Cylindrol A5 showed moderate antimicrobial activity against Bacillus
      subtilis, Kocuria rhizophila, Mycobacterium smegmatis and Acholeplasma laidlawii.
      The biosynthetic pathway to cylindrol A5 was deduced from the 14 isolated
      metabolites of the fungal strain.

PMID- 23168405
TI  - Prevalence and antimicrobial susceptibility of anaerobes from patients with
      periodontal abscess in China.

PMID- 23168406
TI  - Antifungal activity of the primycin complex and its main components A1, A2 and C1
      on a Candida albicans clinical isolate, and their effects on the dynamic plasma
      membrane changes.
AB  - The in vitro antifungal activities of the macrolide lactone antibiotic complex
      primycin (PC) and its main components, A1 (50%), A2 (7.3%) and C1 (13%), against
      the opportunistic pathogenic fungus Candida albicans 33erg(+)were determined by
      microdilution testing. The MIC(100) (the minimal concentration required for 100%
      growth inhibition) values found, A2 (2 MUg ml(-1)), PC (32 MUg ml(-1)), A1 (32
      MUg ml(-1)) and C1 (64 MUg ml(-1)), suggested that the biological activity of PC
      is highly dependent on the proportions of its constituents. In vivo measurements
      of the biophysical properties of plasma membranes were carried out by electron
      paramagnetic resonance (EPR) spectroscopic methods, using the spin probe 5-(4,4
      dimethyloxazolidine-N-oxyl)stearic acid. Conventional EPR measurements
      demonstrated altered phase transition temperatures (Tm) of the plasma membrane of
      strain 33erg(+) as a consequence of treatment with PC or its constituents: for
      cells treated with 128 MUg ml(-1) PC, A1, A2 or C1 for 15 min, Tm was 17, 21,
      14.5 and 15  degrees C, respectively; that is significantly higher than the Tm of
      untreated cells, 12  degrees C. The molecular motions of the near-surface
      hydrophobic region of the plasma membrane, estimated by saturation transfer EPR
      spectroscopy, reflected changes in the membrane phases after the treatment. Two
      physiological membrane phases were detected in control samples: liquid-ordered
      and liquid-disordered, characterized by molecular movements ~10(-6)-10(-8) s and
      >=10(-9) s. The cells treated with the investigated compounds showed the strong
      presence of a non-physiological gel phase additional to the above phases,
      characterized by movements <=10(-5) s.

PMID- 23168407
TI  - Spirohexalines, new inhibitors of bacterial undecaprenyl pyrophosphate synthase,
      produced by Penicillium brasilianum FKI-3368.
AB  - An enzyme assay for bacterial undecaprenyl pyrophosphate (UPP) synthase was
      performed to screen microbial culture broths for inhibitors of UPP synthase.
      During the course of this screening program, an EtOH extract of a rice culture of
      Penicillium brasilianum FKI-3368 was found to inhibit UPP synthase activity. From
      activity-guided purification, a new compound-designated spirohexaline was
      isolated together with the structurally related and known viridicatumtoxin by
      ethyl acetate extraction silica gel and octadecylsilane column chromatographies
      and high-performance liquid chromatography. The structure of spirohexaline was
      elucidated by spectroscopic analysis, including NMR. Spirohexaline and
      viridicatumtoxin have a common hexacycline structure produced by fusion of a
      tetracycline-type ring with a spiro-type ring. They inhibited UPP synthase
      activity with IC50 values of 9.0 and 4.0 MUM, respectively.

PMID- 23168408
TI  - Mode of cell death induction by pharmacological vacuolar H+-ATPase (V-ATPase)
      inhibition.
AB  - The vacuolar H(+)-ATPase (V-ATPase), a multisubunit proton pump, has come into
      focus as an attractive target in cancer invasion. However, little is known about
      the role of V-ATPase in cell death, and especially the underlying mechanisms
      remain mostly unknown. We used the myxobacterial macrolide archazolid B, a potent
      inhibitor of the V-ATPase, as an experimental drug as well as a chemical tool to
      decipher V-ATPase-related cell death signaling. We found that archazolid induced
      apoptosis in highly invasive tumor cells at nanomolar concentrations which was
      executed by the mitochondrial pathway. Prior to apoptosis induction archazolid
      led to the activation of a cellular stress response including activation of the
      hypoxia-inducible factor-1alpha (HIF1alpha) and autophagy. Autophagy, which was
      demonstrated by degradation of p62 or fusion of autophagosomes with lysosomes,
      was induced at low concentrations of archazolid that not yet increase pH in
      lysosomes. HIF1alpha was induced due to energy stress shown by a decline of the
      ATP level and followed by a shutdown of energy-consuming processes. As silencing
      HIF1alpha increases apoptosis, the cellular stress response was suggested to be a
      survival mechanism. We conclude that archazolid leads to energy stress which
      activates adaptive mechanisms like autophagy mediated by HIF1alpha and finally
      leads to apoptosis. We propose V-ATPase as a promising drugable target in cancer
      therapy caught up at the interplay of apoptosis, autophagy, and
      cellular/metabolic stress.

PMID- 23168409
TI  - Peroxisome proliferator-activated receptor alpha positively regulates complement
      C3 expression but inhibits tumor necrosis factor alpha-mediated activation of C3
      gene in mammalian hepatic-derived cells.
AB  - Complement C3 is a pivotal component of three cascades of complement activation.
      The liver is the main source of C3 in circulation and expression and secretion of
      C3 by hepatocytes is increased during acute inflammation. However, the mechanism
      of the regulation of the C3 gene in hepatocytes is not well elucidated. We showed
      that the C3 gene is the direct target for peroxisome proliferator-activated
      receptor alpha (PPARalpha) in human hepatoma HepG2 cells and mouse liver. Using
      PPARalpha siRNA and synthetic PPARalpha agonist WY-14643 and antagonist MK886 we
      showed that activation of PPARalpha results in up-regulation of C3 gene
      expression and protein secretion by HepG2 cells. The PPAR response element
      (PPRE), which is able to bind PPARalpha in vitro and in vivo, was found in the
      human C3 promoter. PPRE is conserved between human and mouse, and WY-14643
      stimulates mouse C3 expression in the liver. TNFalpha increases C3 gene via NF
      kappaB and, to a lesser extent, MEK1/2 signaling pathways, whereas TNFalpha
      mediated stimulation of C3 protein secretion depends on activation of MEK1/2,
      p38, and JNK in HepG2 cells. Activation of PPARalpha abolishes TNFalpha-mediated
      up-regulation of C3 gene expression and protein secretion due to interference
      with NF-kappaB via PPRE-dependent mechanism in HepG2 cells. TNFalpha decreases
      PPARalpha protein content via NF-kappaB and MEK1/2 signaling pathways and
      inhibits PPARalpha binding with the human C3 promoter in HepG2 cells. These
      results suggest novel mechanism controlling C3 expression in hepatocytes during
      acute phase inflammation and demonstrate a crosstalk between PPARalpha and
      TNFalpha in the regulation of complement system.

PMID- 23168410
TI  - Increase in serum Ca2+/Mg2+ ratio promotes proliferation of prostate cancer cells
      by activating TRPM7 channels.
AB  - TRPM7 is a novel magnesium-nucleotide-regulated metal current (MagNuM) channel
      that is regulated by serum Mg(2+) concentrations. Changes in Mg(2+) concentration
      have been shown to alter cell proliferation in various cells; however, the
      mechanism and the ion channel(s) involved have not yet been identified. Here we
      demonstrate that TRPM7 is expressed in control and prostate cancer cells.
      Supplementation of intracellular Mg-ATP or addition of external 2
      aminoethoxydiphenyl borate inhibited MagNuM currents. Furthermore, silencing of
      TRPM7 inhibited whereas overexpression of TRPM7 increased endogenous MagNuM
      currents, suggesting that these currents are dependent on TRPM7. Importantly,
      although an increase in the serum Ca(2+)/Mg(2+) ratio facilitated Ca(2+) influx
      in both control and prostate cancer cells, a significantly higher Ca(2+) influx
      was observed in prostate cancer cells. TRPM7 expression was also increased in
      cancer cells, but its expression was not dependent on the Ca(2+)/Mg(2+) ratio per
      se. Additionally, an increase in the extracellular Ca(2+)/Mg(2+) ratio led to a
      significant increase in cell proliferation of prostate cancer cells when compared
      with control cells. Consistent with these results, age-matched prostate cancer
      patients also showed a subsequent increase in the Ca(2+)/Mg(2+) ratio and TRPM7
      expression. Altogether, we provide evidence that the TRPM7 channel has an
      important role in prostate cancer and have identified that the Ca(2+)/Mg(2+)
      ratio could be essential for the initiation/progression of prostate cancer.

PMID- 23168411
TI  - Novel association between vasoactive intestinal peptide and CRTH2 receptor in
      recruiting eosinophils: a possible biochemical mechanism for allergic
      eosinophilic inflammation of the airways.
AB  - We explored the relation between vasoactive intestinal peptide (VIP), CRTH2, and
      eosinophil recruitment. It is shown that CRTH2 expression by eosinophils from
      allergic rhinitis (AR) patients and eosinophil cell line (Eol-1 cells) was up
      regulated by VIP treatment. This was functional and resulted in exaggerated
      migratory response of cells against PGD2. Nasal challenge of AR patients resulted
      in a significant increase of VIP contents in nasal secretion (ELISA), and the
      immunohistochemical studies of allergic nasal tissues showed significant
      expression of VIP in association with intense eosinophil recruitment. Biochemical
      assays showed that VIP-induced eosinophil chemotaxis from AR patients and Eol-1
      cells was mediated through the CRTH2 receptor. Cell migration against VIP was
      sensitive to protein kinase C (PKC) and protein kinase A (PKA) inhibition but not
      to tyrosine kinase or p38 MAPK inhibition or calcium chelation. Western blot
      demonstrated a novel CRTH2-mediated cytosol-to-membrane translocation of PKC
      epsilon, PKC-delta, and PKA-alpha, -gamma, and -IIalphareg in Eol-1 cells upon
      stimulation with VIP. Confocal images and FACS demonstrated a strong association
      and co-localization between VIP peptide and CRTH2 molecules. Further, VIP induced
      PGD2 secretion from eosinophils. Our results demonstrate the first evidence of
      association between VIP and CRTH2 in recruiting eosinophils.

PMID- 23168412
TI  - Distinct roles of Ser-764 and Lys-773 at the N terminus of von Willebrand factor
      in complex assembly with coagulation factor VIII.
AB  - Complex formation between coagulation factor VIII (FVIII) and von Willebrand
      factor (VWF) is of critical importance to protect FVIII from rapid in vivo
      clearance and degradation. We have now employed a chemical footprinting approach
      to identify regions on VWF involved in FVIII binding. To this end, lysine amino
      acid residues of VWF were chemically modified in the presence of FVIII or
      activated FVIII, which does not bind VWF. Nano-LC-MS analysis showed that the
      lysine residues of almost all identified VWF peptides were not differentially
      modified upon incubation of VWF with FVIII or activated FVIII. However, Lys-773
      of peptide Ser-766-Leu-774 was protected from chemical modification in the
      presence of FVIII. In addition, peptide Ser-764-Arg-782, which comprises the
      first 19 amino acid residues of mature VWF, showed a differential modification of
      both Lys-773 and the alpha-amino group of Ser-764. To verify the role of Lys-773
      and the N-terminal Ser-764 in FVIII binding, we employed VWF variants in which
      either Lys-773 or Ser-764 was replaced with Ala. Surface plasmon resonance
      analysis and competition studies revealed that VWF(K773A) exhibited reduced
      binding to FVIII and the FVIII light chain, which harbors the VWF-binding site.
      In contrast, VWF(S764A) revealed more effective binding to FVIII and the FVIII
      light chain compared with WT VWF. The results of our study show that the N
      terminus of VWF is critical for the interaction with FVIII and that Ser-764 and
      Lys-773 have opposite roles in the binding mechanism.

PMID- 23168413
TI  - Selective amplification of classical and atypical prions using modified protein
      misfolding cyclic amplification.
AB  - With the development of protein misfolding cyclic amplification (PMCA), the topic
      of faithful propagation of prion strain-specific structures has been constantly
      debated. Here we show that by subjecting brain material of a synthetic strain
      consisting of a mixture of self-replicating states to PMCAb, selective
      amplification of PrP(Sc) could be achieved, and that PMCAb mimicked the
      evolutionary trend observed during serial transmission in animals. On the other
      hand, using modified PMCAb conditions that employ partially deglycosylated PrP(C)
      (dgPMCAb), an alternative transmissible state referred to as atypical protease
      resistant form of the prion protein (atypical PrPres) was selectively amplified
      from a mixture. Surprisingly, when hamster-adapted strains (263K and Hyper) were
      subjected to dgPMCAb, their proteinase K digestion profile underwent a dramatic
      transformation, suggesting that a mixture of atypical PrPres and PrP(Sc) might be
      present in brain-derived materials. However, detailed analysis revealed that the
      proteinase K-resistant profile of PrP(Sc) changed in response to dgPMCAb. Despite
      these changes, the 263K strain-specific disease phenotype was preserved after
      passage through dgPMCAb. This study revealed that the change in PrP(Sc)
      biochemical phenotype does not always represent an irreversible transformation of
      a strain, but rather demonstrated the existence of a wide range of variation for
      strain-specific physical features in response to a change in prion replication
      environment. The current work introduced a new PMCA technique for amplification
      of atypical PrPres and raised a number of questions about the need for a clever
      distinction between actual strain mutation and variation of strain-specific
      features in response to a change in the replication environment.

PMID- 23168414
TI  - Computed tomography coronary angiography in patients with acute myocardial
      infarction without significant coronary stenosis.
AB  - BACKGROUND: It is known that a significant number of patients experiencing an
      acute myocardial infarction have normal coronary arteries or nonsignificant
      coronary disease at coronary angiography (CA). Computed tomography coronary
      angiography (CTCA) can identify the presence of plaques, even in the absence of
      significant coronary stenosis. This study evaluated the role of 64-slice CTCA in
      detecting and characterizing coronary atherosclerosis in these patients. METHODS
      AND RESULTS: Consecutive patients with documented acute myocardial infarction but
      without significant coronary stenosis at CA underwent late gadolinium-enhanced
      magnetic resonance and CTCA. Only the 50 patients with an area of myocardial
      infarction identified by late gadolinium-enhanced magnetic resonance were
      included in the study. All of the coronary segments were assessed for the
      presence of plaques. CTCA identified 101 plaques against the 41 identified by CA:
      61 (60.4%) located in infarct-related arteries (IRAs) and 40 (39.6%) in non-IRAs.
      In the IRAs, 22 plaques were noncalcified, 17 mixed, and 22 calcified; in the non
      IRAs, 5 plaques were noncalcified, 8 mixed, and 27 calcified (P=0.005). Mean
      plaque area was greater in the IRAs than in the non-IRAs (6.1+/-5.4 mm(2) versus
      4.2+/-2.1 mm(2); P=0.03); there was no significant difference in mean percentage
      stenosis (33.5%+/-14.6 versus 31.7%+/-12.2; P=0.59), but the mean remodeling
      index was significantly different (1.25+/-0.41 versus 1.08+/-0.21; P=0.01).
      CONCLUSIONS: CTCA detects coronary plaques in nonstenotic coronary arteries that
      are underestimated by CA, and identifies a different distribution of plaque types
      in IRAs and non-IRAs. It may therefore be valuable for diagnosing coronary
      atherosclerosis in acute myocardial infarction patients without significant
      coronary stenosis.

PMID- 23168415
TI  - Smoking gun theory: angiographically normal or mild coronary plaque as a cause of
      myocardial infarction.

PMID- 23168416
TI  - Chiral one-dimensional O-P-O bridged Mn(III)-Schiff base complexes.
AB  - Two couples of enantiomerically pure metal phosphonates are successfully
      synthesized by using chiral Mn(III)-Schiff base mononuclear precursors. Compounds
      [Mn((R,R)-5-Brsalcy)(2-FC(6)H(4)PO(3)H)].3H(2)O (1) and [Mn((R,R)-5-Brsalcy)(4
      CH(3)C(6)H(4)PO(3)H)].CH(3)OH.H(2)O (3) [5-Brsalcy = N,N'-(1,2
      cyclohexanediylethylene)bis(5-bromosalicylideneiminato) dianion] are
      isostructural and show similar one-dimensional chain structures where the
      Mn((R,R)-5-Brsalcy)(+) species are bridged by O-P-O units. Compounds 2 and 4 are
      (S,S)-enantiomers of 1 and 3, respectively. These compounds are all optically
      active, exhibiting second harmonic generation responses 0.3 times that of urea.
      The magnetic measurements of 1 and 3 reveal that dominant antiferromagnetic
      interactions are mediated between the Mn(III) centers.

PMID- 23168417
TI  - Mapping bacterial functional networks and pathways in Escherichia Coli using
      synthetic genetic arrays.
AB  - Phenotypes are determined by a complex series of physical (e.g. protein-protein)
      and functional (e.g. gene-gene or genetic) interactions (GI)(1). While physical
      interactions can indicate which bacterial proteins are associated as complexes,
      they do not necessarily reveal pathway-level functional relationships1. GI
      screens, in which the growth of double mutants bearing two deleted or inactivated
      genes is measured and compared to the corresponding single mutants, can
      illuminate epistatic dependencies between loci and hence provide a means to query
      and discover novel functional relationships(2). Large-scale GI maps have been
      reported for eukaryotic organisms like yeast(3-7), but GI information remains
      sparse for prokaryotes(8), which hinders the functional annotation of bacterial
      genomes. To this end, we and others have developed high-throughput quantitative
      bacterial GI screening methods(9, 10). Here, we present the key steps required to
      perform quantitative E. coli Synthetic Genetic Array (eSGA) screening procedure
      on a genome-scale(9), using natural bacterial conjugation and homologous
      recombination to systemically generate and measure the fitness of large numbers
      of double mutants in a colony array format. Briefly, a robot is used to transfer,
      through conjugation, chloramphenicol (Cm) - marked mutant alleles from engineered
      Hfr (High frequency of recombination) 'donor strains' into an ordered array of
      kanamycin (Kan) - marked F- recipient strains. Typically, we use loss-of-function
      single mutants bearing non-essential gene deletions (e.g. the 'Keio'
      collection(11)) and essential gene hypomorphic mutations (i.e. alleles conferring
      reduced protein expression, stability, or activity(9, 12, 13)) to query the
      functional associations of non-essential and essential genes, respectively. After
      conjugation and ensuing genetic exchange mediated by homologous recombination,
      the resulting double mutants are selected on solid medium containing both
      antibiotics. After outgrowth, the plates are digitally imaged and colony sizes
      are quantitatively scored using an in-house automated image processing
      system(14). GIs are revealed when the growth rate of a double mutant is either
      significantly better or worse than expected(9). Aggravating (or negative) GIs
      often result between loss-of-function mutations in pairs of genes from
      compensatory pathways that impinge on the same essential process(2). Here, the
      loss of a single gene is buffered, such that either single mutant is viable.
      However, the loss of both pathways is deleterious and results in synthetic
      lethality or sickness (i.e. slow growth). Conversely, alleviating (or positive)
      interactions can occur between genes in the same pathway or protein complex(2) as
      the deletion of either gene alone is often sufficient to perturb the normal
      function of the pathway or complex such that additional perturbations do not
      reduce activity, and hence growth, further. Overall, systematically identifying
      and analyzing GI networks can provide unbiased, global maps of the functional
      relationships between large numbers of genes, from which pathway-level
      information missed by other approaches can be inferred(9).

PMID- 23168418
TI  - A highly sensitive gold nanoparticle-based colorimetric probe for pyrophosphate
      using a competition assay approach.
AB  - In this study, a mixture of [Zn(2)(1,3-bis[bis(2
      pyridylmethyl)aminomethyl]benzene)](4+) ([Zn(2)(BBPAB)](4+)) and 11
      mercaptoundecylphosphoric acid functionalized gold nanoparticles (Phos-AuNPs) is
      shown to be a highly sensitive colorimetric probe that can easily detect
      pyrophosphate (PPi) at less than 200 nM with the naked eye.

PMID- 23168421
TI  - Understanding the erythrocyte storage lesion.

PMID- 23168422
TI  - Epidural anesthesia at the Pitie-Salpetriere Hospital: from Fernand Cathelin
      (1901) to Jeanne Seebacher (1974).

PMID- 23168423
TI  - Lactate clearance in the acutely traumatized patient.

PMID- 23168424
TI  - Ombredanne inhaler 1908-1982(?).

PMID- 23168425
TI  - The Henry and Jouvelet transfusion apparatus 1934.

PMID- 23168427
TI  - Radium and thorium applications for the general public: unexpected consequences
      of the discovery from Pierre and Marie Curie.

PMID- 23168426
TI  - Inhaled nitric oxide attenuates the adverse effects of transfusing stored
      syngeneic erythrocytes in mice with endothelial dysfunction after hemorrhagic
      shock.
AB  - BACKGROUND: The authors investigated whether transfusion with stored erythrocytes
      would increase tissue injury, inflammation, oxidative stress, and mortality
      (adverse effects of transfusing stored erythrocytes) in a murine model of
      hemorrhagic shock. They tested whether the adverse effects associated with
      transfusing stored erythrocytes were exacerbated by endothelial dysfunction and
      ameliorated by inhaling nitric oxide. METHODS: The authors studied mice fed a
      high-fat diet (HFD-fed; to induce endothelial dysfunction) or a standard diet for
      4-6 weeks. Mice were subjected to 90 min of hemorrhagic shock, followed by
      resuscitation with leukoreduced syngeneic erythrocytes stored less than 24 h
      (fresh erythrocytes) or stored for 2 weeks (stored erythrocytes). RESULTS: In
      standard-diet-fed mice at 2 h after resuscitation, transfusion with stored
      erythrocytes increased tissue injury more than transfusion with fresh
      erythrocytes. The adverse effects of transfusing stored erythrocytes were more
      marked in HFD-fed mice and associated with increased lactate levels and short
      term mortality. Compared with fresh erythrocytes, resuscitation with stored
      erythrocytes was associated with a reduction in P50, increased plasma hemoglobin
      levels, and increased indices of inflammation and oxidative stress, effects that
      were exacerbated in HFD-fed mice. Inhaled nitric oxide reduced tissue injury,
      lactate levels, and indices of inflammation and oxidative stress and improved
      short-term survival in HFD-fed mice resuscitated with stored erythrocytes.
      CONCLUSIONS: Resuscitation with stored erythrocytes adversely impacts outcome in
      mice with hemorrhagic shock, an effect that is exacerbated in mice with
      endothelial dysfunction. Inhaled nitric oxide reduces tissue injury and improves
      short-term survival in HFD-fed mice resuscitated with stored erythrocytes.

PMID- 23168428
TI  - Paul Bert: from physiology to barometric pressure.

PMID- 23168429
TI  - Musicotherapy in anesthesia: Maxime Drossner, 1901.

PMID- 23168430
TI  - Prognostic significance of blood lactate and lactate clearance in trauma
      patients.
AB  - BACKGROUND: Lactate has been shown to be a prognostic biomarker in trauma.
      Although lactate clearance has already been proposed as an intermediate endpoint
      in randomized trials, its precise role in trauma patients remains to be
      determined. METHODS: Blood lactate levels and lactate clearance (LC) were
      calculated at admission and 2 and 4 h later in trauma patients. The association
      of initial blood lactate level and lactate clearance with mortality was tested
      using receiver-operating characteristics curve, logistic regression using triage
      scores, Trauma Related Injury Severity Score as a reference standard, and
      reclassification method. RESULTS: The authors evaluated 586 trauma patients (mean
      age 38+/-16 yr, 84% blunt and 16% penetrating, mortality 13%). Blood lactate
      levels at admission were elevated in 327 (56%) patients. The lactate clearance
      should be calculated within the first 2 h after admission as LC0-2 h was
      correlated with LC0-4 h (R=0.55, P<0.001) but not with LC2-4 h (R=0.04, not
      significant). The lactate clearance provides additional predictive information to
      initial blood lactate levels and triage scores and the reference score. This
      additional information may be summarized using a categorical approach (i.e., less
      than or equal to -20 %/h) in contrast to initial blood lactate. The results were
      comparable in patients with high (5 mM/l or more) initial blood lactate.
      CONCLUSIONS: Early (0-2 h) lactate clearance is an important and independent
      prognostic variable that should probably be incorporated in future decision
      schemes for the resuscitation of trauma patients.

PMID- 23168431
TI  - Postoperative obstructive sleep apnea and delirium?

PMID- 23168433
TI  - Should we use psychostimulant drugs to boost the emergence from general
      anesthesia?

PMID- 23168435
TI  - Utility of near-infrared spectroscopy for assessing cerebral oxygen saturation
      during beach chair position.

PMID- 23168437
TI  - Ultrasound investigation and the eye.

PMID- 23168439
TI  - Updated pain guidelines:  what is new?

PMID- 23168441
TI  - Can propofol mimic alcohol-related pain in patients with Hodgkin lymphoma?

PMID- 23168445
TI  - A meta-analysis of cognitive therapy for worry in generalized anxiety disorder.
AB  - We report a meta- and primary data-analysis investigating the efficacy of
      cognitive therapy (CT) for pathological worry in adults with GAD that includes an
      analysis of primary data not reported in previous meta-analyses. Eligible studies
      included those whose participants met the criteria for a diagnosis of GAD and
      those that used the PSWQ as an outcome measure. All eligible studies used a
      randomized controlled design. Analyses included a random-effects meta-analysis of
      between-study effect sizes and hierarchical linear models of both within study
      change over time and primary recovery data. The results show that CT was
      effective in reducing pathological worry when compared with non-therapy controls
      (d=1.81), and gains were largely maintained at follow-up. The magnitude of
      effects reported was larger than previously found, suggesting an increased
      efficacy of newer forms of CT. However, we found weaker evidence to suggest that
      CT for pathological worry was superior to non-CT treatment controls (d=0.63).
      Analysis of primary recovery data revealed that 57% of participants were classed
      as recovered at 12 months following CT, and CT had significantly better recovery
      rates than all other comparison treatments at post-treatment and 12-month follow
      up. These findings support the increasing efficacy of CT as a treatment for GAD.
      However, CT interventions still need further refinement to help a greater
      proportion of sufferers achieve recovery.

PMID- 23168447
TI  - You don't say: dynamic aphasia, another variant of primary progressive aphasia?
AB  - Primary progressive aphasia (PPA) is a language predominant neurodegenerative
      disorder that has three recognized variants: nonfluent/agrammatic, semantic, and
      logopenic. This report describes a 60-year-old man who presented with a
      progressive decline in verbal output that does not fit the currently accepted PPA
      subtypes. The patient exhibited a paucity of verbal output and impaired phonemic
      fluency with minimal associated language, cognitive, or behavioral deficits.
      Focal cortical thinning/hypometabolism of the left superior frontal region and a
      cerebrospinal fluid profile not consistent with Alzheimer's disease pathology
      were identified. This case of isolated progressive dynamic aphasia extends the
      current boundaries of PPA diagnostic variants.

PMID- 23168448
TI  - Symptomatic treatment of memory decline in Alzheimer's disease by deep brain
      stimulation: a feasibility study.
AB  - Recent studies have suggested that memory circuits can be modulated by deep brain
      stimulation (DBS). This propriety might be used to slow down cognitive decline in
      patients suffering from Alzheimer's disease (AD). We conducted a prospective
      study to evaluate the feasibility and safety of DBS in AD patients with mild
      cognitive decline. Inclusion criteria were: patients (<70 years old) with AD
      diagnosed for less than 2 years, predominant impairment of episodic memory, and
      Mini-Mental Status Exam (MMSE) score between 20 and 24. The fornix was stimulated
      bilaterally by electrodes implanted stereotactically in the hypothalamus.
      Clinical, biological, neuropsychological, and imaging evaluations were conducted
      3 months before surgery and 3, 6, and 12 months thereafter. During the one year
      period of inclusion, 110 patients with recently diagnosed AD and predominant
      impairment of episodic memory were screened. Only 9 patients (8.2%) fulfilled all
      the inclusion criteria. Finally, just one patient accepted to be operated
      (acceptance rate 11.1%) and completed the study. No complications occurred and
      the stimulation was perfectly tolerated. After one year of stimulation, the
      memory scores (MMSE, ADAS-Cog, Free and Cued Selective Reminding Test) were
      stabilized compared to baseline, and mesial temporal lobes metabolism increased.
      This pilot study provides new data about the safety of fornix DBS in the
      hypothalamus. However, it suggests that only a small proportion of AD patients
      might be interested in this approach and that the acceptance of DBS by AD
      patients was low, raising questions about the relevance of this approach to meet
      the expectations of these patients.

PMID- 23168449
TI  - Longitudinal analysis of serum copper and ceruloplasmin in Alzheimer's disease.
AB  - BACKGROUND: Several studies have reported that peripheral levels of copper and
      ceruloplasmin (CP) can differentiate patients with Alzheimer's disease (AD) from
      non-AD cases. The aim of this study was to determine the diagnostic value of
      serum copper, CP, and non-CP copper levels in a large cohort of AD subjects.
      METHODS: Serum copper and CP concentrations were measured at baseline and at 18
      months in participants from the Australian Imaging Biomarkers and Lifestyle Study
      of Ageing. Cross-sectional and longitudinal analyses were conducted using both
      univariate and multivariate testing adjusting for age, gender, total protein, and
      ApoE epsilon4 genotype status. RESULTS: There was no significant difference in
      levels of serum copper or CP between the AD and healthy control groups, however,
      we identified a near-significant decrease in non-CP copper in the mild cognitive
      impairment and AD groups at baseline (p = 0.02) that was significant at 18-months
      (p = 0.003). CONCLUSION: Our results suggest that there may be decreased non-CP
      copper levels in mild cognitive impairment and AD, which is consistent with
      diminished copper-dependent biochemical activities described in AD.

PMID- 23168450
TI  - Long-term exercise modulates hippocampal gene expression in senescent female
      mice.
AB  - The senescence-accelerated SAMP8 mouse is considered a useful non-transgenic
      model for studying aspects of progressive cognitive decline and Alzheimer's
      disease (AD). Using SAMR1 mice as controls, here we explored the effects of 6
      months of voluntary wheel running in 10-month-old female SAMP8 mice. Exercise in
      SAMP8 mice improved phenotypic features associated with premature aging (i.e.,
      skin color and body tremor) and enhanced vascularization and BDNF gene expression
      in the hippocampus compared with controls. With the aim of identifying genes
      involved in brain aging responsive to long-term exercise, we performed whole
      genome microarray studies in hippocampus from sedentary SAMP8 (P8sed), SAMR1
      (R1sed), and exercised SAMP8 (P8run) mice. The genes differentially expressed in
      P8sed versus R1sed were considered as putative aging markers (i) and those
      differentially expressed in P8run versus P8sed were considered as genes modulated
      by exercise (ii). Genes differentially expressed in both comparisons (i and ii)
      were considered as putative aging genes responsive to physical exercise. We
      identified 34 genes which met both criteria. Gene ontology analysis revealed that
      they are mainly involved in functions related to extracellular matrix
      maintenance. Selected genes were validated by real-time quantitative PCR assays,
      i.e., collagen type 1 alpha 1 (col1a1), collagen type 1 alpha 2 (col1a2),
      fibromodulin (fmod), prostaglandin D(2) synthase (ptgds), and aldehyde
      dehydrogenase (Aldh1a2). As a whole, our study suggests that exercise training
      during adulthood may prevent or delay gene expression alterations and processes
      associated with hippocampal aging in at-risk subjects.

PMID- 23168451
TI  - Letter by D'Anna et al regarding article, "Long-term mortality in patients with
      stroke of undetermined etiology".

PMID- 23168452
TI  - High-risk plaque for carotid artery stenting evaluated with 3-dimensional T1
      weighted gradient echo sequence.
AB  - BACKGROUND AND PURPOSE: Preventing cerebral embolisms is a major concern with
      carotid artery stenting (CAS). This study evaluated 3-dimensional T1-weighted
      gradient echo (3D T1GRE) sequence to predict cerebral embolism related to CAS.
      METHODS: We performed quantitative analyses of the characteristics of 47 carotid
      plaques before CAS by measuring the signal intensity ratio (SIR) and plaque
      volume using 3D T1GRE images. We used T1-weighted turbo field echo sequence to
      obtain 3D T1GRE images. We also evaluated diffusion-weighted images (DWI) of the
      brain before and after CAS to detect ischemic lesions (DWI lesions) from cerebral
      emboli. RESULTS: SIR (2.17 [interquartile range 1.50-3.07] versus 1.35
      [interquartile range 1.08-1.97]; P=0.010) and plaque volume (456 mm(3)
      [interquartile range 256-696] versus 301 mm(3) [interquartile range 126-433];
      P=0.008) were significantly higher in the group of patients positive for DWI
      lesions (P-group: n=26) than DWI lesion-negative patients (N-group: n=21). In
      multivariate logistic regression analysis, SIR (P=0.007) and plaque volume
      (P=0.042) were independent predictors of DWI lesions with CAS. Furthermore, SIR
      (rs=0.42, P=0.005) and plaque volume (rs=0.36, P=0.012) were positively
      correlated with the number of DWI lesions. From analysis of a receiver-operating
      characteristic curve, the most reliable cutoff values of SIR and plaque volume to
      predict DWI lesions related to CAS were 1.80 and 373 mm(3), respectively.
      CONCLUSIONS: Quantitative evaluation of carotid plaques using 3D T1GRE images may
      be useful in predicting cerebral embolism related to CAS.

PMID- 23168453
TI  - CXCR4 antagonist AMD3100 protects blood-brain barrier integrity and reduces
      inflammatory response after focal ischemia in mice.
AB  - BACKGROUND AND PURPOSE: Inflammatory response plays a critical role in
      propagating tissue damage after focal cerebral ischemia. CXCL12 is a key
      chemokine for leukocyte recruitment. However, the role of CXCL12 and its receptor
      CXCR4 in ischemia-induced inflammatory response is unclear. Here we use the
      pharmacological antagonist of CXCR4, AMD3100, to investigate the function of
      CXCL12/CXCR4 in regulating inflammatory response during acute ischemia. METHODS:
      Adult male CD-1 mice (n=184) underwent permanent suture middle cerebral artery
      occlusion (MCAO). AMD3100 was injected for 3 days (1 mg/kg/day) after MCAO. Brain
      water content, infarct volume, neurological score, and myeloperoxidase (MPO)
      expression and activity were examined at 24, 48, and 72 hours after MCAO.
      Proinflammatory cytokine RNA and protein levels in brain tissue were measured by
      RT-PCR and enzyme linked immunosorbent assay. RESULTS: Neurological score was
      greatly improved in AMD3100-treated mice compared with the control mice 3 days
      after MCAO (P<0.05). Brain edema-induced change of water content, IgG protein
      leakage, Evans blue extravasation, occludin, and ZO-1 expression in ipsilateral
      hemisphere were alleviated by acute treatment of AMD3100. MPO expression and
      activity revealed that AMD3100 profoundly reduced the number of MPO-positive
      cells in the ischemic region (P<0.05). It also attenuated proinflammatory
      cytokines including interleukin 6, tumor necrosis factor alpha, and interferon
      gamma; their mRNA and protein levels changed accordingly compared with the
      controls (P<0.05). CONCLUSIONS: CXCR4 antagonist AMD3100 significantly suppressed
      inflammatory response and reduced blood-brain barrier disruption after MCAO.
      AMD3100 attenuated ischemia-induced acute inflammation by suppressing leukocyte
      migration and infiltration, in addition to reducing proinflammatory cytokine
      expression in the ischemic region.

PMID- 23168454
TI  - Correlation of large artery intracranial occlusive disease with carotid intima
      media thickness and presence of carotid plaque.
AB  - BACKGROUND AND PURPOSE: Large artery intracranial occlusive disease (LAICOD) is a
      predominant cause of ischemic stroke in China. Carotid intima-media thickness
      (CIMT) and presence of carotid plaque are also related to subsequent ischemic
      stroke. However, the correlation between these and LAICOD is less clear. METHODS:
      This was a community-based cross-sectional study. All subjects underwent carotid
      duplex ultrasonography and transcranial Doppler. Mean CIMT value of bilateral
      common carotid arteries was used. Plaque was defined as a focal CIMT of >1.5 mm.
      LAICOD in transcranial Doppler was defined by peak systolic velocity and age, and
      presence of turbulence or musical sound was also considered. RESULTS: For the 537
      subjects studied (mean age, 54.7+/-10.1 years; 46.9% males), mean CIMT was 0.74+/
      0.12 mm, with the 75th percentile of 0.80 mm. CIMT >=1.0 mm was identified in 13
      subjects (2.4%). Plaques were detected in 79 subjects (14.7%). Compared with
      those without LAICOD, the 48 subjects (8.9%) with LAICOD had greater CIMTs
      (0.77+/-0.09 versus 0.73+/-0.12 mm; P=0.044), more with CIMT of higher quartiles
      (P=0.007), and more with carotid plaques (25.0% versus 13.7%; P=0.035). However,
      after adjusting for confounding factors, CIMT and presence of carotid plaque were
      not significantly associated with LAICOD. CONCLUSIONS: The results suggest that
      CIMT and presence of carotid plaque probably are not independently correlated
      with LAICOD in Chinese community residents, which supported the existence of
      pathologic and pathophysiologic differences in atherogenesis of intra- and
      extracranial arteries.

PMID- 23168455
TI  - Postal and face-to-face administration of stroke outcome measures: can mixed
      modes be used?
AB  - BACKGROUND AND PURPOSE: Different modes of administration are used to collect
      stroke outcomes, even within the same study, potentially leading to different
      results. We investigated the effect of administration mode (postal questionnaire;
      face-to-face interview) on self-reports of activities of daily living and mood.
      METHODS: The study was nested within a poststroke motivational interviewing
      trial. Activities of daily living (Barthel; Nottingham Extended) and mood
      (General Health Questionnaire; Yale) were collected at 3 and 12 months via postal
      questionnaire. Participants were approached to respond again via face-to-face
      interview. Paired t tests (McNemar test) and intraclass correlation coefficients
      (Cohen kappa) were used, with 95% CI, to compare scores (items). RESULTS: Forty
      four participants consented. Only Barthel scores were significantly different;
      they were 1.0 (95% CI, 0.5-1.6) higher face-to-face. The intraclass correlation
      coefficient for the Barthel was 0.90; for the other scales it was between 0.83
      and 0.87. The Yale kappa was 0.72. CONCLUSIONS: Modes of administration might be
      used interchangeably, albeit in conjunction with corrections for the Barthel.

PMID- 23168457
TI  - Endobronchial Ultrasound: Is it Ready for Prime Time?

PMID- 23168456
TI  - Atrial fibrillation in ischemic stroke: predicting response to thrombolysis and
      clinical outcomes.
AB  - BACKGROUND AND PURPOSE: Atrial fibrillation (AF) increases the risk of stroke and
      is associated with poor stroke outcomes. Limited tools are available to evaluate
      clinical outcomes and response to thrombolysis in stroke patients with AF.
      METHODS: We applied the iScore (http://www.sorcan.ca/iscore), a validated risk
      score, to consecutive patients with an acute ischemic stroke admitted to stroke
      centers in the Registry of the Canadian Stroke Network. The main outcome
      considered was a favorable outcome (defined as a modified Rankin scale 0-2) at
      discharge after thrombolysis. Secondary outcomes included intracerebral
      hemorrhage, death at 30 days, and at 1 year stratified by terciles of the iScore.
      RESULTS: Among 12 686 patients with an acute ischemic stroke, 2185 (17.2%) had
      AF. Overall, AF patients had higher risk of death at 30 days (22.3% versus 10.2%;
      P<0.0001), 1 year (37.1% versus 19.5%; P<0.0001) and death or disability at
      discharge (69.7% versus 54.7%; P<0.0001) compared with non-AF patients. After
      adjustment, thrombolysis was associated with a favorable outcome for patients
      without AF (relative risk, 1.18; 95% CI, 1.10-1.27), but no benefit was observed
      for patients with AF (relative risk, 0.91; 95% CI, 0.71-1.17). There was a
      modestly increased risk of intracranial hemorrhage (any type) (16.5% versus
      11.6%; relative risk, 1.42; 95% CI, 1.05-1.91) after thrombolysis among AF
      compared with non-AF patients. In the logistic regression analysis, there was an
      interaction between tPA and iScore for a favorable outcome (P-value interaction
      <0.001). The interaction also was significant (P<0.0012) among patients without
      AF, but did not reach significance (P=0.17) in patients with AF. CONCLUSIONS:
      Stroke patients with AF have higher mortality, greater risk of intracerebral
      hemorrhage, and a similar response trend to thrombolysis compared with non-AF
      patients.

PMID- 23168458
TI  - MDCT Airway Assessment: Now a Critical Part of the Bronchoscopist's Tool Kit.

PMID- 23168459
TI  - Central Airway Obstruction Masquerading as Difficult-to-Treat Asthma: A
      Retrospective Study.
AB  - BACKGROUND AND OBJECTIVES: Large airway obstruction is well described as a cause
      of apparent asthma, unresponsive to the standard asthma therapy. Our purpose is
      to introduce multiple variants of other diseases that mimic asthma with failure
      to treat. METHODS: Between the years 2005 and 2008, clinical data from 16
      patients with difficult-to-treat asthma (from 3200 patients who were evaluated in
      our ward for any reason) were reviewed at Massih Daneshvary Hospital. RESULT: Of
      the 16 patients, 5 were men and 11 women. Mean age was 40.43 years (40.43+/
      SD=16.49). Dyspnea was present in 93.75% of the patients. Chest x-ray was normal
      in 62.5% of patients. Computerized tomography scan was normal in 18.75% of the
      patients. Endobronchial lesion was found in 87.5% of patients in which 50% was
      benign and 50% malignant. Vocal cord dysfunction was found in 6.25% of the
      patients whereas 6.25% had external pressure on tracheal lumen. Mean duration of
      asthma treatment was 23.8 months (range, 3 to 96 mo). CONCLUSIONS: Asthma
      masqueraders include several conditions that may confound a correct diagnosis of
      asthma. A careful clinical examination, high index of suspicion, and appropriate
      analysis of spirometry are essential for the appropriate diagnosis and management
      of asthma. If there is no improvement after appropriate treatment, further
      evaluation should be performed.

PMID- 23168460
TI  - Assessment of Chemosensitivity-related Aberrant Methylation of Nonsmall Cell Lung
      Cancer by EBUS-TBNA.
AB  - BACKGROUND: Multigene aberrant methylation profiling may predict response to
      chemotherapy in lung cancer. The purpose of this study was to analyze the
      feasibility of detecting aberrant methylation in biopsy samples obtained by
      endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA).
      METHODS: Lymph node samples from 30 patients with nonsmall cell lung cancer
      diagnosed as metastatic carcinoma by EBUS-TBNA were analyzed. Histologic cores
      obtained by EBUS-TBNA were separately stored at -80 degrees C. DNA was extracted
      from EBUS-TBNA samples and bisulfate modification was performed. We evaluated the
      methylation status of a panel of 6 genes (FANCF, Reprimo, TMS1/ASC, activated
      protein-2alpha, CHFR, and ATM) using methylation-specific polymerase chain
      reaction. Twenty-four patients with adenocarcinoma or squamous cell carcinoma
      metastasis received platinum-based combination chemotherapy. We reviewed their
      response to chemotherapy in correlation to the methylation status. RESULTS:
      Bisulfate modification was successfully performed in all samples using DNA
      obtained from EBUS-TBNA samples by checking p16 unmethylation expression.
      Aberrant methylation was detected as follows: 9 cases of FANCF (30.0%), 14 cases
      of Reprimo (46.7%), 10 cases of TMS1/ASC (33.3%), and 19 cases of activated
      protein-2alpha (63.3%). In response to chemotherapy, there were 1 complete
      response, 6 partial response, 12 stable disease, and 5 progressive disease (PD)
      cases. The number of methylated genes was significantly smaller in the PD group
      than in the non-PD groups (P=0.0435). CONCLUSIONS: Aberrant methylation analysis
      can be performed in metastatic lymph nodes sampled by EBUS-TBNA. EBUS-TBNA allows
      for genetic evaluations of tumor cells and may help to guide the most effective
      treatment strategies in the near future.

PMID- 23168461
TI  - Novel use of a disposable curved stent insertion plastic device for silicone
      stent placement in patients with limited neck extension.
AB  - As granulation tissue formation frequently complicates the insertion of metallic
      tracheobronchial stents in patients with longer life expectancy, the inert
      silicone tracheobronchial stent remains the treatment of choice for inoperable
      benign tracheal stenosis. Similarly, the Y silicone stent insertion also plays an
      important role for refractory malignant stenoses involving the carina and
      tracheobronchial junction. The classic insertion method of a straight or Y
      silicone stent requires rigid bronchoscopy under general anesthesia with a
      hyperextended neck. This is not an option for patients with limited neck
      extension. We report a novel method of silicone stent insertion using a
      disposable curved stent insertion plastic device to solve the problem in 2
      patients. The new device may have a role in managing patients with central airway
      obstruction but limited neck extension. As a valuable alternative to conventional
      rigid bronchoscope, it also adds to the ease of the silicone stent placement.

PMID- 23168462
TI  - Endobronchial Ultrasound-directed Transbronchial Needle Aspiration in Diagnosis
      of Mediastinal Lesions: Initial Egyptian Experience.
AB  - Mediastinal lesions represent a diagnostic challenge and often require invasive
      approaches. We evaluated the role of radial probe endobronchial ultrasound
      directed transbronchial needle aspiration (EBUS-TBNA) in the evaluation of
      mediastinal lesions. Between March 2005 to February 2006, 30 consecutive patients
      with enlarged mediastinal lymph nodes from unknown etiologies or suspicious for
      metastatic bronchogenic carcinoma and mediastinal masses underwent EBUS-TBNA and
      were clinically followed up. EBUS-TBNA was applied under topical anesthesia,
      midazolam sedation with a mean dose of 4.6+1.7 mg and prolonged the examination
      by 14.7 minutes on average. EBUS-directed TBNA was performed in 17 lymph nodes
      and 13 mediastinal masses, achieving specific diagnosis in 82.3% (14/17) and
      84.6% (11/13) of examined lesions, respectively, with an overall yield of 83%.
      The sensitivity, specificity, and accuracy of EBUS-TBNA in distinguishing benign
      from malignant mediastinal lesions were 89.4%, 100%, and 93.3%, respectively.
      EBUS was well tolerated by most of the patients with no TBNA-related
      complications. In conclusion, EBUS-TBNA of mediastinal lesions is a minimally
      invasive safe diagnostic technique with high yield, even in the hands of those
      with initial experience. This initial study is convincing and stimulating for
      widespread application of EBUS-TBNA in Egyptian bronchoscopy practice.

PMID- 23168463
TI  - Biopsy of peripheral pulmonary lesions using real-time radial endobronchial
      ultrasound and a "double-barrel" bronchoscope.
AB  - Endobronchial ultrasound (EBUS) has contributed substantially to the diagnosis of
      centrally located lesions within the thorax. More recently, this technology has
      been applied to the diagnosis of peripheral pulmonary lesions. One accepted
      technique for visualizing peripheral pulmonary lesions using radial EBUS involves
      use of a guide sheath placed within or adjacent to the lesion after localization
      using a radial EBUS probe. A diagnostic yield of >70% has been reported using
      this method, though direct visual feedback of needle aspiration within the mass
      is still lacking. Under continuous ultrasound guidance, the diagnostic yield of
      linear array EBUS is higher than 90%. In this case series, we present 3 cases in
      which transbronchial needle aspiration and forceps biopsy of peripheral pulmonary
      lesions were performed under continuous radial EBUS guidance using a modified
      "double-barrel" bronchoscope.

PMID- 23168464
TI  - The Long-term Prognosis of Patients With the Diagnosis of Nonmalignant Pleural
      Effusions After Pleuroscopy.
AB  - PURPOSE: Several studies have demonstrated the diagnostic yield of medical
      thoracoscopy (pleuroscopy) in making the diagnosis of malignant pleural effusion
      (MPE). No previous studies, however, have reported long-term outcomes for
      patients undergoing diagnostic pleuroscopy in whom no malignancy was demonstrated
      either with cytologic examination of pleural fluid or pathologic examination of
      thoracoscope-guided pleural biopsies. We report the results of long-term follow
      up (at least 3 y) of patients with the diagnosis of nonmalignant pleural
      effusions (NMPEs) after pleuroscopy. METHODS: One hundred and nineteen patients
      underwent the procedure between 1994 and 2003 at Lahey Clinic. We report a
      retrospective review of 25 of those patients diagnosed with NMPE after diagnostic
      pleuroscopy. All 25 patients underwent thoracoscopic pleural biopsy and cytologic
      examination of the effusion. Outcomes were assessed using review of the medical
      records, appointment scheduler, social security death index, and/or telephone
      conversation with primary care providers. RESULTS: Mean age+/-SD was 68 years
      (range, 34 to 87 y). Median survival time was estimated at 114 months.
      Concomitant illness was also evaluated: 40% (n=10) diabetes, 64% (n=16) coronary
      artery disease, 40% (n=10) congestive heart failure, 20% (n=5) liver disease, 20%
      (n=5) renal disease, and 36% (n=9) pulmonary disease. Final diagnoses after
      pleuroscopy most commonly included chronic pleuritis (n=7) and pleural plaques
      (n=5). Survival was found at 1 year to be 88% (22/25), 3 years 80% (20/25), and 5
      years 74.7% (19/25). None of the 25 patients developed subsequent MPE.
      CONCLUSIONS: Patients with NMPE after pleuroscopy have a favorable prognosis and
      are unlikely to be subsequently diagnosed with an MPE.

PMID- 23168465
TI  - Multidetector-row Computed Tomography of Diffuse Tracheal Disease: Pictorial
      Review.
AB  - Diffuse tracheal diseases are uncommon and may mimic asthma or other forms of
      chronic obstructive lung disease. Bronchoscopy is usually definitive in
      establishing a diagnosis and assessing the severity of diffuse tracheal disease.
      However, advances in multidetector-row computed tomography (MDCT) technology
      allow for rapid acquisition time and generation of high-quality multiplanar
      reconstructions and virtual bronchoscopic images, making MDCT evaluation of
      suspected or known tracheal disease the noninvasive examination of choice. The
      MDCT findings of the various diseases that diffusely affect the trachea may be
      highly suggestive of 1 particular disease or narrow the differential diagnosis to
      a few possibilities. Moreover, MDCT imaging of the chest can help identify
      associated lung disease or complications of diffuse tracheal disease such as
      pneumonia or atelectasis. This pictorial review illustrates the MDCT appearances
      of the more common diffuse tracheal diseases.

PMID- 23168466
TI  - Endobronchial band.
AB  - A 52-year-old man underwent a diagnostic bronchoscopy for right hilar mass and
      ipsilateral upper lobe endobronchial lesion. During the procedure, a
      nonobstructing endobronchial tissue band was found on the left main bronchus just
      before the secondary carina. This tissue formation, of uncertain etiology, did
      not obstruct the airway or compromise the clearance of secretions and for these
      reasons it was left intact.

PMID- 23168467
TI  - Bronchial mucoepidermoid carcinoma.
AB  - We report a case of a minimally fluoro-2-deoxy-D-glucose avid bronchial
      mucoepidermoid tumor in a young male heavy smoker who presented with hemoptysis
      and a normal chest x-ray.

PMID- 23168468
TI  - A case with multifocal masses.
AB  - A 70-year-old man presented with progressive dyspnea, chest and back pain,
      fatigue of 5 years' duration, and dysphagia and weight loss of 1 year's duration.
      Despite multiple diagnostic work-ups performed previously, no eventual diagnosis
      could have been made. His personal past history was remarkable for impaired
      vision and recurrent "pneumonias" over the last 3 years. Computed tomography
      revealed mediastinal, right pulmonary, and retroperitoneal masses. The
      mediastinal mass compressed and obstructed the airways, superior vena cava, right
      main pulmonary artery, and esophagus, whereas the retroperitoneal mass encased
      inferior vena cava, abdominal aorta, and ureters. Transbronchial needle
      aspiration and endobronchial biopsy by rigid bronchoscopy and surgical biopsies
      of the mediastinal and pulmonary masses all showed inflammatory fibrous tissue.
      Ophthalmologic examination revealed a right orbital pseudotumor. A diagnosis of
      multifocal fibrosclerosis was made and corticosteroid treatment started. However,
      the patient died 2 weeks after establishing the diagnosis.

PMID- 23168469
TI  - Tracheal web: presentation of a case with uncommon features.
AB  - Postintubation tracheal web is a rarely encountered complication of endotracheal
      intubation. Although few of them remain asymptomatic until diagnosed
      accidentally, most of them present with symptoms of acute airway obstruction and
      even death. We present here a case of postintubation tracheal web with uncommon
      features, including a very long delay in diagnosis despite a 99% obstruction of
      the tracheal lumen.

PMID- 23168470
TI  - Endobronchial leiomyoma: case report and literature review.
AB  - Endobronchial leiomyomas are rare benign tumors of the lung, arising from the
      smooth muscle of the bronchial tree. Symptomatology is based on the degree of
      endoluminal bronchial obstruction, and surgical resection has generally been the
      mainstay of treatment. We describe a mechanically ventilated patient with
      recurrent atelectasis and a postobstructive pneumonia caused by an occlusive
      endobronchial leiomyoma who was successfully weaned off the ventilator after
      treatment with argon plasma coagulation delivered via flexible bronchoscopy. We
      also briefly review the literature.

PMID- 23168471
TI  - Left tracheal bronchus in an infant with laryngeal cleft.
AB  - Laryngeal cleft, a rare congenital anomaly, may occur in association with other
      airway abnormalities. Despite the close proximity of embryologic development of
      the laryngotracheobronchial tree, bronchial abnormalities in association with
      laryngeal cleft have not been widely reported. We describe the left tracheal
      bronchus, an uncommon anomaly of the tracheobronchial tract, in an infant with
      laryngeal cleft. Coexistence of rare tracheobronchial anomalies needs to be
      considered in the presence of laryngeal cleft. Early recognition of tracheal
      bronchus may prevent complications of endotracheal intubation and improve the
      management of potential complications such as recurrent pneumonia, atelectasis,
      and hemoptysis.

PMID- 23168472
TI  - Pulmonary pleomorphic carcinoma mimicking bronchopneumonia in an elderly man.
AB  - A 77-year-old male smoker presented with fever, cough, and night sweat of 4
      weeks' duration. Imaging of the chest revealed a left lung consolidation and a
      right cavitary lesion. Further investigation with flexible bronchoscopy supported
      the diagnosis of an infectious/inflammatory process. The patient clinically
      improved with antibiotics and was discharged. He was readmitted with a similar
      presentation 2 weeks later; at this time he had new onset of atrial fibrillation
      and worsening respiratory symptoms. After his heart rate was controlled, he
      underwent transthoracic needle aspiration and pleural fluid drainage, which again
      were nondiagnostic. A surgical biopsy was scheduled, but he expired before
      surgery. Necropsy revealed pulmonary pleomorphic carcinoma with invasion of both
      the lungs, lymph nodes, pericardium, and myocardium. Clinicians should keep a
      high index of suspicion for pleomorphic carcinoma in those patients with unusual
      presentation or progressive or nonresolving pulmonary infiltrates. Early surgical
      intervention, either for diagnosis or treatment, is imperative due to the
      aggressive nature of the tumor and the dismal prognosis.

PMID- 23168473
TI  - Initial Diagnosis of Mediastinal Lymph Node Metastases From Prostate Cancer by
      Endobronchial Ultrasound-guided Transbronchial Needle Aspiration.
AB  - A 61-year-old patient with multiple enlarged mediastinal and hilar lymph nodes
      (?3a, ?4R, ?7, and ?11) and no abnormal shadows in the lung field by chest
      computed tomography was referred to our department for further evaluation.
      Endobronchial ultrasound-guided transbronchial needle aspiration was performed;
      cytology revealed adenocarcinoma, whereas histology contained adenocarcinoma of
      prostate origin. Immunohistochemistry was strongly positive for prostate-specific
      antigen and prostate-specific acid phosphate for confirmation of metastases from
      the prostate cancer and negative for thyroid transcription factor-1. Hence, the
      patient was diagnosed as having lymph node metastasis from a prostate cancer.
      After the initial diagnosis, needle biopsy of the prostate was performed, and
      prostate cancer was confirmed. The patient received hormonal therapy and has
      remained in stable condition. Endobronchial ultrasound-guided transbronchial
      needle aspiration provides tissue for histologic examination, including
      immunohistochemistry, from mediastinal and hilar lymph nodes involved with
      metastasis from a distal primary site.

PMID- 23168474
TI  - Unusual cause of chronic cough in an immunocompetent host.
AB  - Aspergillus infections cause a spectrum of pulmonary diseases depending on the
      immune status of the host. We report a rare case of a young, immunocompetent,
      patient who developed Aspergillus tracheobronchitis. Owing to primary resistance
      to itraconazole, the disease progressed to aspergilloma despite treatment. The
      condition was successfully treated with oral voriconazole.

PMID- 23168475
TI  - Short-term Placement of Multiple Self-expandable Metallic Stents for the
      Treatment of Bilateral Bronchial Dehiscences Complicating Lung Transplantation.
AB  - Bronchial dehiscence after lung transplantation is a rare complication yet has
      high morbidity and mortality. The majority of the patients are not surgical
      candidates. We present the case of a 59-year-old man with bilateral lung
      transplantation for interstitial pulmonary fibrosis who was readmitted with
      symptoms of acute rejection and severe hypoxemic respiratory failure on day 14.
      Bronchoscopy showed bilateral bronchial anastomotic dehiscences. A computerized
      tomography scan showed evidence of significant peribronchial air collection in
      the pleural space and the mediastinum. Owing to a high predictive operative
      mortality, endobronchial management was planned, and 3 uncovered self-expanding
      metallic stents (Ultraflex, Boston Scientific Corp) were placed (in the left main
      stem bronchus, the anterior segment of the right upper lobe, and the right
      intermediate bronchus). At 5 weeks bronchoscopy showed complete healing of the
      dehiscences with granulation. The stents were then removed by rigid bronchoscopy.
      Three weeks after the stent removal a bronchoscopic examination showed a normal
      tracheobronchial tree except for a slightly narrowed right anastomosis. We
      conclude that short-term placement of uncovered self-expanding metallic stents
      provides a safe and minimally invasive option in the management of bilateral
      dehiscences.

PMID- 23168476
TI  - Overlooked foreign body: eighteen years inside the bronchus.
AB  - A long-standing undiagnosed foreign body bronchus in an adult is very rare. We
      report a rare case of an overlooked foreign body in the bronchus. A 38-year-old
      man presented with the complaints of chronic cough with expectoration and
      wheezing for the last 18 years. Computed tomography of the chest detected a
      foreign body in the right lower lobar bronchus. Detailed history revealed that
      the patient had aspirated a whistle 18 years earlier that was overlooked by the
      treating clinicians. It remained undiagnosed in chest radiographs. It was
      extracted using a rigid bronchoscope. We emphasize the need to remain vigilant
      for endobronchial foreign bodies in patients with persistent cough and wheeze.

PMID- 23168477
TI  - Granular cell tumor of trachea.
AB  - Granular cell tumors of the tracheobronchial tree are rare benign lesions of
      neurogenic origin. These benign tumors mostly involve the skin, oral cavity, or
      esophagus. There is no consensus regarding treatment of granular cell tumors.
      Treatment varies from simple observation to different bronchoscopic
      interventions, such as laser therapy or fulguration to surgical resection.

PMID- 23168478
TI  - Endobronchial Ultrasound-guided Transbronchial Needle Aspiration in the Diagnosis
      of Metastatic Thyroid Cancer.
AB  - Since its first application in 1992, endobronchial ultrasound, in conjunction
      with transbronchial needle aspiration, has proven to be an efficient tool for
      lung cancer staging. Furthermore, significant benefits have also been shown in
      the diagnosis of other mediastinal diseases, such as pulmonary sarcoidosis and
      lymphoma. Its use in the diagnosis of solitary intrapulmonary tumors and
      preoperative assessment of tracheobronchial invasion from thyroid cancer has also
      been reported. We present a case of metastatic papillary thyroid cancer diagnosed
      by endobronchial ultrasound-guided transbronchial needle aspiration in a patient
      with a paratracheal mass. In this case, neither surgical biopsy nor
      transcutaneous needle biopsy was an option due to a complicated past surgical
      history and the location of the mass.

PMID- 23168479
TI  - Dr chevalier jackson saved my life.

PMID- 23168480
TI  - Unusual endobronchial foreign body.

PMID- 23168488
TI  - Toxicity evaluation of individual and mixed enniatins using an in vitro method
      with CHO-K1 cells.
AB  - Enniatins (ENs) A, A1, B and B1 are produced by Fusarium species. They are known
      as emerging fusariotoxins, and can cause outbreaks in both humans and animals.
      ENs elicits a wide range of different biological properties and toxicological
      effects, and their co-occurrence may enhance the extent of these hazards. As the
      potential toxins reach in vitro cells in the same way as they would in vivo,
      cytotoxicity was studied with CHO-K1, which is considered one of the most
      sensitive cell lines for preliminary screening of cytotoxicity studies. In this
      study, individual cytotoxic effects of ENs were evaluated by MTT assay after
      exposing ENs to CHO-K1 cells for 24, 48, and 72h. The IC50 values obtained for
      ENs A, A1, B and B1 ranged from >7.5 to 2.83+/-0.49, from 8.8+/-2.29 to 1.65+/
      0.06, from 11.0+/-2.65 to 2.80+/-0.16 and from 4.53+/-1.23 to 2.47+/-0.29MUM,
      respectively. The ENs cytotoxic interaction was evaluated by the isobologram
      method. The IC50 values for ENs combination ranged from 0.44+/-0.15 (ENs A1+B1)
      to 0.97+/-0.48 (ENs A1+B+B1). The binary combinations ENs A+B1, ENs A1+B and ENs
      B+B1 showed additive effect thought all concentrations tested. Sinergistic effect
      of combined ENs A+A1, A+B, A1+B1, A+A1+B, A+A1+B1, A+B+B1 and A1+B+B1 at higher
      concentrations occurred. Synergism effect (CI from 0.37+/-0.08 to 0.74+/-0.22)
      was observed at higher concentrations with binary and tertiary combinations of EN
      A, while antagonism effect was obtained at lower concentrations for ENs A+A1+B1
      (CI=2.67+/-1.32) and ENs A1+B+B1 (CI=3.14+/-1.91). These results provide
      quantitative evidence that ENs cytotoxicity depend on their concentrations, and
      also on their combination with other mycotoxins.

PMID- 23168489
TI  - A dynamic system for single and repeated exposure of airway epithelial cells to
      gaseous pollutants.
AB  - In vitro models are promising approaches to investigate the adverse effects and
      the mode of action of air pollutants on the respiratory tract. We designed a
      dynamic system that allows the single or repeated exposure of cultured cells to
      two major indoor air gaseous pollutants, formaldehyde (HCHO) and nitrogen dioxide
      (NO2), alone or as a mixture. In this system, the Calu-3 human bronchial
      epithelial cell line was exposed at the air-liquid interface (ALI) or submerged
      by culture medium to synthetic air or to target concentrations of HCHO and/or NO2
      once or on 4 consecutive days before assessment of cell viability and necrosis,
      IL-6 and IL-8 release and trans-epithelial electrical resistance. Our data showed
      that whereas the ALI method can be used for single short-term exposures only, the
      submerged method provides the possibility to expose Calu-3 cells in a repeated
      manner. As well, we found that repeated exposures of the cells to HCHO and NO2 at
      concentrations that can be found indoors triggered a significant decrease in cell
      metabolism and an increase in IL-8 release that were not evoked by a single
      exposure. Thus, our work highlights the fact that the development of systems and
      methods that allow repeated exposures of cultured cells to gaseous compounds in
      mixtures is of major interest to evaluate the impact of air pollution on the
      respiratory tract.

PMID- 23168490
TI  - Beyond the fourth wave of genome-wide obesity association studies.
AB  - Obesity and related complications are major health burdens. Almost 700 million
      adults are currently obese globally and the prevalence is predicted to rise
      towards 2030. The sudden change of lifestyle with physical inactivity and
      excessive calorie intake undoubtedly have a major part of the epidemic
      development; however, some individuals seem to be more prone to be affected by an
      unhealthy lifestyle than others. Hence, genetic predisposition also has an
      essential role in determining disease susceptibility and response to lifestyle
      factors. Since the introduction of genome-wide association studies (GWAS), the
      success of identifying obesity susceptibility variants have increased, and a
      total of 32 variants have been identified associating genome-wide significantly
      with body mass index (BMI) and 18 with measures of fat distribution during four
      overall obesity GWAS waves. However, the immediate success of the GWAS approach
      has eased off, but the proportion of explained variance for BMI by the identified
      obesity variants remains low. This review suggests and discusses new initiatives
      to take GWAS of obesity to the next level, including gene-environment
      interactions as modulating/masking factors, low-frequent or rare variants and
      ways to address such analyses, and finally reflections about the applicability of
      epigenetic modifications when elucidating the genetic background of obesity.

PMID- 23168493
TI  - Switchable 3D networks by light controlled pi-stacking of azobenzene macrocycles.
AB  - Azobenzene macrocycles were designed for switchable pi-stacking interaction.
      After efficient preparation and characterization of azobenzene macrocycles
      containing electron rich as well as electron poor elements a dimeric analogue was
      synthesized, which formed reversibly 3D-networks. Gel formation was observed with
      aromatic solvents representing the first example of this type based on switchable
      azobenzene macrocycles.

PMID- 23168491
TI  - Hypnosis for cancer care: over 200 years young.
AB  - Answer questions and earn CME/CNE Hypnosis has been used to provide psychological
      and physical comfort to individuals diagnosed with cancer for nearly 200 years.
      The goals of this review are: 1) to describe hypnosis and its components and to
      dispel misconceptions; 2) to provide an overview of hypnosis as a cancer
      prevention and control technique (covering its use in weight management, smoking
      cessation, as an adjunct to diagnostic and treatment procedures, survivorship,
      and metastatic disease); and 3) to discuss future research directions. Overall,
      the literature supports the benefits of hypnosis for improving quality of life
      during the course of cancer and its treatment. However, a great deal more work
      needs to be done to explore the use of hypnosis in survivorship, to understand
      the mediators and moderators of hypnosis interventions, and to develop effective
      dissemination strategies.

PMID- 23168492
TI  - LYRM7/MZM1L is a UQCRFS1 chaperone involved in the last steps of mitochondrial
      Complex III assembly in human cells.
AB  - The mammalian Complex III (CIII) assembly process is yet to be completely
      understood. There is still a lack in understanding of how the structural subunits
      are put together and which additional factors are involved. Here we describe the
      identification and characterization of LYRM7, a human protein displaying high
      sequence homology to the Saccharomyces cerevisiae protein Mzm1, which was
      recently shown as an assembly factor for Rieske Fe-S protein incorporation into
      the yeast cytochrome bc(1) complex. We conclude that human LYRM7, which we
      propose to be renamed MZM1L (MZM1-like), works as a human Rieske Fe-S protein
      (UQCRFS1) chaperone, binding to this subunit within the mitochondrial matrix and
      stabilizing it prior to its translocation and insertion into the late CIII
      dimeric intermediate within the mitochondrial inner membrane. Thus, LYRM7/MZM1L
      is a novel human CIII assembly factor involved in the UQCRFS1 insertion step,
      which enables formation of the mature and functional CIII enzyme.

PMID- 23168495
TI  - A quick access to the spirotricyclic core analogue of mangicol A by a Rh(I)
      catalyzed tandem Pauson-Khand/[4+2] cycloaddition.
AB  - Highly chemoselective and stereoselective tandem Pauson-Khand/[4+2] cycloaddition
      leads to efficient construction of the spirotricyclic core analogue of mangicol
      A.

PMID- 23168494
TI  - Quantitative screening of genes regulating tryptophan hydroxylase transcription
      in Caenorhabditis elegans using microfluidics and an adaptive algorithm.
AB  - Forward genetic screening via mutagenesis is a powerful method for identifying
      regulatory factors in target pathways in model organisms such as the soil
      dwelling free-living nematode Caenorhabditis elegans (C. elegans). Currently
      manual microscopy is the standard technique for conducting such screens; however,
      it is labor-intensive and time-consuming because screening requires imaging
      thousands of animals. Recently microfluidic chips have been developed to increase
      the throughput of some of such experiments; nonetheless, most of these chips are
      multilayer devices and complicated to fabricate and therefore prone to failure
      during fabrication and operation. In addition, most sorting decisions are made
      manually and the criteria used for sorting are subjective. To overcome these
      limitations, we developed a simple single-layer microfluidic device and an
      adaptive algorithm to make sorting decisions. The one-layer device greatly
      improves the reliability, while quantitative analysis with the adaptive algorithm
      allows for the identification of mutations that generate subtle changes in
      expression, which would have been hard to detect by eye. The screening criterion
      is set based on the mutagenized population, not separate control populations
      measured prior to actual screening experiments, to account for stochasticity and
      day-to-day variations of gene expression in mutagenized worms. Moreover, during
      each experiment, the threshold is constantly updated to reflect the balance
      between maximizing sorting rate and minimizing false-positive rate. Using this
      system, we screened for mutants that have altered expression levels of tryptophan
      hydroxylase, a key enzyme for serotonin synthesis in a CaMKII gain-of-function
      background. We found several putative mutants in this screen. Furthermore, this
      microfluidic system and quantitative analysis can be easily adapted to study
      other pathways in C. elegans.

PMID- 23168496
TI  - Relationship between mean platelet volume and mitral annular calcification.
AB  - Mitral annular calcification (MAC) is associated with several cardiovascular
      disorders including coronary artery disease (CAD), atherosclerosis, heart
      failure, and stroke. MAC and atherosclerosis share similar clinical risk factors
      for cardiovascular diseases, including age, obesity, hypertension,
      hyperlipidemia, and diabetes mellitus. The aim of this study was to assess the
      mean platelet volume (MPV), an indicator of platelet activation in patients with
      MAC. The study group consisted of 101 patients with MAC. An age, sex, and BMI
      matched control group was composed of 55 patients who were admitted to the
      echocardiography laboratory due to suspicion of organic heart disease and
      eventually found to be free of MAC. We measured platelet indices values in
      patients and controls. MPV was significantly higher in patients with MAC than in
      controls (8.9 +/- 0.8 versus 8.0 +/- 0.9 fl, respectively; P < 0.001) and
      platelet distribution width (PDW) was significantly higher in patients with MAC
      than in controls (15.8 +/- 1.3 versus 15.0 +/- 1.3%, respectively; P < 0.001).
      MPV was positively correlated with MAC (P < 0.001, r = 0.47), atrial fibrillation
      (P = 0.01, r = 0.19), left atrial (P = 0.02, r = 0.83) and negatively correlated
      with platelet count (P = 0.01, r = -0.20). MPV [odds ratio (OR) 3.89; 95%
      confidence interval (CI) 1.97-7.67; P < 0.0001], and PDW (OR 2.27; 95% CI 1.45
      3.55; P < 0.0001) were independently associated with the MAC. We have shown that
      MPV and PDW were significantly elevated in patients with MAC. MPV was correlated
      with MAC, atrial fibrillation and left atrial and negatively correlated with
      platelet count. MPV and PDW were independently associated with MAC.

PMID- 23168498
TI  - Nasal manifestations of immunoglobulin G4-related disease.
AB  - OBJECTIVES/HYPOTHESIS: Immunoglobulin (Ig)G4-related disease is a systemic
      syndrome, characterized by sclerosing lesions that mainly affect the exocrine
      tissue. Although some patients with IgG4-related disease complain of nasal
      symptoms, there are few reports concerning the nasal manifestations of this
      disease. We investigated the clinical and pathological features of the nasal
      manifestations of IgG4-related disease. STUDY DESIGN: Retrospective review in a
      tertiary referral hospital. METHODS: Twenty-three consecutive patients with IgG4
      related disease, six allergic rhinitis (AR) patients, and eight healthy subjects
      (HS) were evaluated. Nasal symptoms, local findings of the nasal cavity, and
      laboratory data were examined. Mucosal tissues from the inferior turbinate were
      obtained from all subjects before treatment. The level of IgG4-positive plasma
      cells and other infiltrating cells, and the number of nasal glands in the nasal
      subjects were compared among the three groups. RESULTS: Ten (43.4%) of 23 cases
      had some nasal symptoms, such as nasal obstruction and nasal crusting. Thirteen
      cases (56.5%) had numerous IgG4-positive plasma cell infiltration in the nasal
      mucosa. IgG4-positive plasma cells, CD3, and CD4 were significantly higher in the
      IgG4-related disease group than in the HS and AR groups, whereas the number of
      nasal glands in the IgG4-related disease group was significantly lower than in
      the HS and AR groups. CONCLUSIONS: The inflammatory lesions associated with IgG4
      related disease exist on the nasal membrane. Thus, the nasal manifestations of
      IgG4-related disease were thought to be different from AR.

PMID- 23168499
TI  - Instrumental methods in the diagnostics of locked-in syndrome.
AB  - The locked-in syndrome (LiS) is typically characterized by a paralysis of almost
      all body muscles combined with intact cognitive functions. In practice, there are
      often additional brain damages besides the one directly causing LiS. These
      damages can lead to cognitive impairment, which substantially complicates the
      diagnosis of LiS. At the level of behavior, therefore, the disease can be
      confused with akinetic mutism, vegetative state (syn. unresponsive wakefulness
      state) and some other conditions. Using instrumental methods in addition to
      behavioral diagnostics helps to avoid diagnostic errors and to improve prognosis
      of rehabilitation of such patients. These methods, which include measurements of
      brain electric or magnetic fields, electrical potential of muscles, blood flow
      and oxygen consumption in the brain, are reviewed in this paper.

PMID- 23168501
TI  - Barotrauma from novel endobronchial ablation techniques.

PMID- 23168500
TI  - Chronic bilateral T1 denervation in women with macromastia.
AB  - INTRODUCTION: The objective of this study was to identify the pattern of
      neurological deficits and document electrophysiological changes in women with
      macromastia. METHODS: Patients with macromastia and neurological complaints
      underwent clinical evaluation and electrodiagnostic (EDx) studies of the upper
      limbs. RESULTS: Findings include low-amplitude medial antebrachial cutaneous
      (MACN) sensory nerve action potentials (SNAPs) and median compound muscle action
      potentials (CMAPs) and chronic denervation changes in the bilateral abductor
      pollicis brevis (APB) muscles on needle electrode examination (NEE), indicating
      axonal loss in the bilateral T1 distribution. CONCLUSIONS: The EDx data are in
      keeping with lesions involving bilateral T1 anterior primary rami (APR).
      Potential sites of compromise of the T1 APR are discussed. Further study of the
      effect of treatment for macromastia on the clinical and EDx findings is proposed.

PMID- 23168502
TI  - Therapeutic bronchoscopic intervention with resector balloon.
AB  - In this study a novel therapeutic bronchoscopic technique, balloon bronchoplasty
      with resector balloon, was used in 128 procedures for 112 consecutive patients
      with airway obstruction from lung cancer or granulation tissue. All procedures,
      except 4, were performed with a rigid bronchoscope under general anesthesia. The
      remainder were performed with a flexible bronchoscope under local anesthesia. In
      all procedures, balloon bronchoplasty was the primary method and we achieved 100%
      success with no major immediate or long-term complications. The technique also
      facilitated submucosal and distal tumor resection. We found balloon bronchoplasty
      using resector balloon to be a safe, effective, fast, easy, and potentially cost
      effective method in the management of airway obstruction from endobronchial
      submucosal lesions.

PMID- 23168503
TI  - Immediate spirometric alterations after bronchoscopy in diffuse lung disease.
AB  - OBJECTIVE: To evaluate the spirometric alterations after bronchoscopy with
      bronchoalveolar lavage (BAL) and bronchoscopic lung biopsy in patients with
      diffuse lung disease (DLD). PATIENTS AND METHODS: Twenty-three patients with DLD
      and 6 individuals with solitary pulmonology nodule or dyspnea were subjected to
      BAL with the infusion of 4 aliquots of 50 mL of saline solution at room
      temperature; 3 to 5 bronchoscopic lung biopsy specimens were obtained from the
      locations based on chest x-ray and/or tomogram findings. Spirometry was perfomed
      before and 10, 30, and 60 minutes after the bronchoscopic procedure. RESULTS: A
      meaningful spirometric decrease within the group with DLD and in the control
      group was observed, being more intense 10 minutes after the completion of the
      examination, followed by a natural tendency of returning to initial baseline
      values after 60 minutes. The DLD group presented a more significant decrease
      (P<0.05) in: forced vital capacity 14.4%, forced expiratory volume in the first
      second 12.7%, peak expiratory flow rate 15.9%, forced expiratory flow at 50%
      volume 13.6%, and peripheral saturation of oxygen 3.6%. Despite the decrease in
      the spirometry, the group with DLD presented only minor complications, such as
      transitory hypoxemia and bleeding. CONCLUSIONS: Our results suggest that
      bronchoscopy associated with BAL and bronchoscopic lung biopsy is a safe
      procedure in patients with restrictive lung diseases, despite a decrease in their
      spirometric values.

PMID- 23168504
TI  - Ultrasound-guided Fine Needle Aspiration Biopsy of Pleural-based Intrathoracic
      Lesions.
AB  - BACKGROUND: Pleural-based intrathoracic lesions pose a diagnostic challenge.
      Image-guided percutaneous biopsy with fluoroscopy, computed tomography (CT) scan,
      and ultrasound (US) have been used to establish a diagnosis. We report the yield
      of US-guided fine needle aspiration biopsy (FNAB) of these lesions at our center.
      METHODS: Twenty patients with pleural-based intrathoracic lesions underwent US
      guided FNAB. All were considered to have an unresectable malignant process based
      on clinical evaluation. Nineteen patients had pleural-based parenchymal lesion
      and 1 had an anterior mediastinal mass touching the chest wall. RESULTS: Twenty
      patients underwent 21 US-guided FNAB procedures. A final diagnosis was
      established in all the patients: 19 malignancies and 1 benign lesion. US-guided
      FNAB established a diagnosis of malignancy in 17 of 19 patients (89.5%) in the
      first attempt. In 1 patient, a diagnosis of malignancy was made on a repeat US
      guided FNAB, increasing the overall yield to 18 of 19 (95%). In 1 patient with a
      nondiagnostic US-guided FNAB, a diagnosis of malignancy was established with CT
      scan-guided FNAB. US-guided FNAB was able to diagnose 15 of 16 cases of non-small
      cell carcinoma and 3 of 3 (100%) small cell carcinoma. In 1 patient with benign
      lesion, US-guided FNAB showed pulmonary macrophages. This patient was diagnosed
      as having pneumonia after antibiotic therapy and repeat CT scan showed complete
      resolution. For a diagnosis of malignancy, US-guided FNAB had 94.7% sensitivity,
      100% specificity, 95% diagnostic accuracy, 100% positive predictive value, and
      50% negative predictive value. There were no major complications. CONCLUSIONS: US
      guided FNAB of pleural-based intrathoracic lesions is a rapid, simple, and safe
      procedure with a high yield for malignancy.

PMID- 23168505
TI  - Low-dose Talc Plus Low-dose Doxycycline for Pleuroscopic Pleurodesis: Initial
      Experience.
AB  - OBJECTIVE: We performed a retrospective review of the use of the combination of
      talc and doxycycline for pleurodesis in patients. METHODS: There were 33
      sequential cases over a 2-year period. Doses of doxycycline (250 mg) and talc
      (2.5 g) were half the "usual" doses. RESULTS: Thirty-three cases were identified
      (20 women, 13 men, average age 64 y). No immediate perioperative complications
      were noted. Chest tube duration averaged 4.2+/-2.6 days. Total drainage averaged
      880 mL. Length of stay after procedure in the outpatient group was 4.8+/-3.1
      days. Eleven patients (33%) reported persistence or worsening dyspnea in the
      immediate postoperative period. Only 2 developed respiratory distress; neither
      had any parenchymal changes on chest radiology or required ventilatory support.
      Other immediate postoperative events included chest pain in 18 patients (54%) and
      fever in 3. Follow-up imaging was available for 29 patients, an average of 3.9
      months postoperatively. Twenty patients (69%) had complete pleurodesis, 4
      patients (14%) had partial pleurodesis, and 5 (17%) failed. In no case did follow
      up imaging demonstrate new adult respiratory distress-like infiltrates.
      CONCLUSIONS: The combination of low-dose doxycycline with low-dose talc appears
      to be a safe and rational approach to pleuroscopic pleurodesis in patients. The
      success rate matched that of the literature for talc alone. The side-effect
      profile was reasonable. No severe sequelae were observed. A prospective clinical
      trial seems warranted.

PMID- 23168506
TI  - Safety of topical tetracaine in patients undergoing flexible bronchoscopy.
AB  - Lidocaine is currently the most commonly used topical anesthetic during flexible
      bronchoscopy (FFB) in North America. Tetracaine, a longer-acting agent, might
      produce better airway analgesia; however, previous literature has suggested that
      tetracaine is more risky and can even result in cardiac arrest. The maximum
      recommended tetracaine dose for topical anesthesia is 20 mg. Over the past 30
      years, our Pulmonary Special Procedures Unit has used topical tetracaine in
      considerably higher doses. In this study, we sought to review the safety of this
      approach. We completed a retrospective review of all FFBs performed on
      nonintubated patients by a single bronchoscopist from January 2005 to February
      2007. The primary outcome variables included adverse reactions and tetracaine
      dose administered. Five hundred thirty-seven FFBs were performed on 431 patients.
      Patient age ranged from 20 to 94 years, with a mean age of 55 years. Eighty-one
      percent (n=434) of these FFBs were performed using only topical anesthesia.
      Tetracaine solution 0.45% was used in 99.6% of these procedures. Mean tetracaine
      dose was 120 mg (range: 18 to 158 mg). No adverse reactions attributable to
      tetracaine were noted. Specifically, no cardiac or neurologic events occurred.
      Bronchospasm was noted in 1.5% of patients and 1 patient required intubation
      after the procedure owing to severe hypoxemia. This retrospective study suggests
      that topical tetracaine at doses up to 8 times the "recommended" dose is safe for
      the use during FFB.

PMID- 23168507
TI  - Minimally invasive talc insufflation: a new technique with no need for
      thoracoscopy.
AB  - Talc insufflation is usually performed by thoracic surgeons in the operating room
      through video-assisted thoracoscopic surgery (VATS) or by pulmonologists in a
      specially equipped suite (medical thoracoscopy). These techniques can cause
      postoperative pain, require placement of port sites through small incisions, and
      increase waiting time and cost for patients who have no need for visual
      inspection of the pleura, biopsy, or apical bleb resection. Poudrage (French for
      powdering) with asbestos-free talcum powder (talc) is a proven technique with
      wide acceptance for treatment of pneumothorax. Use of a small, 4 g, canister of
      talc under pressure is a commonly used method to aerosolize and apply it using
      the supplied Teflon catheters. This report describes a patient who was too ill
      for almost any formal procedure in whom we performed talc poudrage by an even
      less invasive technique, using controlled permissive pneumothorax in the
      radiology suite by using a small needle, guide wire, and dilator with no
      thoracoscopy ports. Given the increased expense, frequent waiting time delay, and
      diminished access to care, we believe this technique deserves consideration in
      patients who are poor surgical candidates and perhaps in the young patient with
      no computed tomography evidence that might suggest the need for apical bleb
      resection, biopsy, or additional investigation.

PMID- 23168508
TI  - Bronchoscopic view of a tuberculosis cavity with actinomyces.
AB  - Coexistence of pulmonary actinomycosis with tuberculosis has rarely been
      reported. The presence of Actinomyces in sputum and bronchoalveolar lavage is
      inadequate for diagnosis, as it may represent mere colonization. Traditionally,
      excisional biopsy is considered to be the gold standard for histologic diagnosis.
      There are multiple case reports in which the diagnosis of pulmonary actinomycosis
      was based on bronchial biopsy and Wang needle aspiration. We describe an
      incidental finding of a bronchial communication with passage of a flexible
      bronchoscope into the tuberculosis cavity. The images reveal a 5-cm cavity with a
      whitish, stone-like structure noticed to move back and forth with respiration.
      Colonies of Actinomyces were seen on transbronchial brushing cytology.
      Bronchoalveolar lavage cultures were negative. To our knowledge such a detailed
      pictorial description of a tuberculosis cavity with Actinomyces has not been
      reported in the past.

PMID- 23168509
TI  - Endotracheal spindle cell lipoma presenting as a chronic cough.
AB  - An elderly gentleman with a chronic cough was found to have a large midtracheal
      lesion on computed tomography scan. Endotracheal extirpation with an
      electrocautery snare successfully removed the lesion. Histologic and
      immunohistochemical analyses revealed the lesion to be a spindle cell lipoma. We
      provide herein the case presentation and management, the differential diagnosis,
      and an overview of spindle cell lipoma.

PMID- 23168510
TI  - A Unique Case of Pulmonary Hyalinizing Granuloma Associated With FDG-avid PET
      Scan and Deep Venous Thrombosis.
AB  - An 83-year-old obese woman with a 60-pack-year smoking history was referred for
      evaluation of an abnormal chest radiograph [chest x-ray (CXR)]. Her past medical
      history was significant for recurrent deep venous thrombosis without any
      predisposing factors. CXR showed a large mass in the right mid lung and another
      nodule at the right apex, highly suspicious for a neoplastic process. These were
      not present on a CXR from 2 years earlier. An fluorodeoxyglucose (FDG)-positron
      emission tomography (PET)/computed tomography (CT) scan revealed that all lesions
      were strongly FDG-avid. Six CT-guided core-needle lung biopsy specimens were
      obtained from the lung mass and all contained dense, lamellar, or "ropy" keloid
      like collagen bundles arranged in a haphazard pattern. The biopsy specimens
      lacked significant necrosis and granulomas. Congo red stain with polarization was
      also negative for amyloid. The diagnosis of pulmonary hyalinizing granuloma (PHG)
      was made. A complete hypercoagulable workup was performed but no underlying
      abnormalities were found, including a negative lupus anticoagulant and malignancy
      workup. The patient was maintained on warfarin and followed with serial CT scans
      for 1 year, with spontaneous regression in the lung mass. The case is unique as
      it is the first case that reports an association of PHG with recurrent deep
      venous thrombosis in the absence of autoimmune or procoagulant factors and
      emphasizes the need for life-long anticoagulation in such scenarios. Also, we
      report the FDG-avid PET scan findings here that are novel for this disease in
      adults and add PHG to the list of diseases causing false-positive PET scans when
      malignancy is suspected.

PMID- 23168511
TI  - A case of 50 pneumonias in 13 years.
AB  - An acquired tracheal pouch or diverticulum can be a sequel to congenital
      esophageal atresia-tracheoesophageal fistula repair. There are variable clinical
      presentations of this complication, which can be misdiagnosed as asthma. We
      report a patient with recurrent pneumonia and chronic cough with history of
      esophageal atresia/tracheoesophageal fistula repair that was dually diagnosed and
      successfully managed.

PMID- 23168512
TI  - Bilateral lemierre syndrome secondary to periodontitis: a case report and review
      of the literature.
AB  - BACKGROUND: Lemierre syndrome is the typical presentation of human
      necrobacillosis. It is characterized by an initial infection, progressing to
      septic thrombophlebitis, septicemia, and multisystem embolic necrotic abscesses.
      It is usually caused by Fusobacterium necrophorum, but its pathophysiology
      remains obscure. A case of bilateral Lemierre syndrome secondary to periodontitis
      is reported. CASE PRESENTATION: A previously healthy 24-year-old African American
      man presented with a 2-week history of fever, chills, dyspnea, abdominal pain and
      vomiting, nonbloody diarrhea, anorexia, and body aches. He occasionally smoked
      marijuana but had no pets, and denied sick contact or recent travel. Physical
      examination was remarkable for tachypnea, tachycardia, pyrexia, icteric sclera,
      dry oral mucosa, moderate-to-severe gingival inflammation, and dental caries
      involving the upper and lower molars. The oropharynx was clear. He had tenderness
      over the sternocleidomastoid muscles bilaterally, and nontender cervical
      lymphadenopathy. Chest examination revealed reduced breath sounds in both bases
      with fine crackles at the right base. Examination of the cardiovascular and
      gastrointestinal systems was significant for tenderness in the right upper
      quadrant with no rebound. Laboratory findings were significant for leukocytosis
      with a left shift, anemia, abnormal liver function tests, elevated creatine
      phosphokinase, and positive blood culture for F. necrophorum. Chest radiographs
      and computed tomography scans revealed multilobar cavitary nodular densities with
      pleural effusions. Duplex sonography of the neck demonstrated thrombosed left
      internal jugular vein with complete occlusion of the lumen, thrombosed left
      subclavian, and axillary veins with minimal blood flow. There was also a small
      thrombus in both the right internal jugular and right subclavian veins with
      partial occlusion of their lumina. He was prescribed penicillin, metronidazole,
      and anticoagulation therapy and had complete resolution of the lung lesions and
      marginal improvement of the bilateral neck thrombophlebitis. He was awaiting
      dental procedures. CONCLUSIONS: A case is reported of extensive bilateral septic
      thrombophlebitis of the deep neck veins secondary to periodontal disease. To the
      best of my knowledge, this is the first case of bilateral Lemierre syndrome due
      to periodontal disease reported in the literature. It highlights the typical
      septic thrombophlebitis of Lemierre syndrome and its protean manifestations, such
      as hepatitis and rhabdomyolysis. This presentation also underscores the
      significance of thorough dental examinations in febrile patients. With respect to
      anticoagulation therapy in Lemierre syndrome, though still not established, there
      is some evidence of utility with no untoward effects.

PMID- 23168513
TI  - Endobronchial tuberculosis: a case report and review of the literature.
AB  - Endobronchial tuberculosis is a rare occurrence in the developed countries. The
      diagnosis is often delayed due to its nonspecific presentation and paucity of
      radiographic findings. The condition is often misdiagnosed as either bronchial
      asthma or lung cancer. The delay in the diagnosis often leads to airway stenosis
      and requires therapeutic bronchoscopy. Here we present 2 cases of endobronchial
      tuberculosis to illustrate our point.

PMID- 23168514
TI  - Subcutaneous emphysema: an unusual presentation of foreign body aspiration.
AB  - Two cases of subcutaneous emphysema owing to foreign body aspiration are
      described. In case 1, a 21/2-year-old boy presented with complaints of
      respiratory distress, cough, and swelling over neck. Computed tomography scan of
      neck and thorax revealed subcutaneous emphysema along with emphysematous changes
      of left lung. In Case 2, a 5-year-old boy presented with left pneumothorax along
      with massive subcutaneous emphysema, extending from the face to the chest.
      Computed tomography scan of the chest revealed subcutaneous emphysema,
      pneumomediastinum, and left pneumothorax. Both of the patients underwent
      bronchoscopic removal of the foreign body from the left main bronchus. At present
      both are asymptomatic and doing well. Subcutaneous emphysema is rare as a
      manifestation of foreign body aspiration and this cause should be kept in mind,
      even in the absence of forthcoming history of aspiration.

PMID- 23168515
TI  - Pulmonary-gastric fistula.
AB  - Pulmonary to gastric fistulae are extremely rare. They can occur secondary to
      infection or malignancy invading through the lung into the pleural space, through
      the diaphragm and into the stomach. The case history reports on the successful
      diagnosis and treatment of a pulmonary to gastric fistula.

PMID- 23168516
TI  - Ease of use of watanabe spigot for alveolopleural fistulas.
AB  - Pulmonary fistulas are associated with a high risk of morbidity and mortality. We
      report 2 cases of alveolopleural fistulas, 1 in a patient with chronic
      hydropneumothorax and the other after wedge biopsy. In both cases, Watanabe
      spigot (Novatech, Grasse, France) was placed for bronchial occlusion with short
      term success.

PMID- 23168517
TI  - A tree grows in bronchus.
AB  - A tracheobronchial foreign body (TFB) can be a life-threatening emergency that
      requires urgent intervention. TFBs occur most commonly in childhood as a result
      of aspiration. Traumatic TFB is not frequently reported in the literature. All
      reported cases of traumatic TFB to date have involved a projectile mechanism of
      injury. We report a case of a patient who presented with recurrent pneumonia.
      Flexible bronchoscopy revealed a TFB partially obstructing the right bronchus
      intermedius. Pathology confirmed the TFB to consist of wood. Further history
      revealed that the patient experienced an impaling injury on a tree sucker more
      than 30 years before presentation. Surgery was required to remove the TFB. This
      case illustrates the importance of the patient's history, and is the first
      reported case of an impaling injury causing a traumatic TFB.

PMID- 23168518
TI  - Massive hemoptysis in a patient with sarcoidosis.
AB  - A 39-year-old African American man presented with massive hemoptysis. He was
      known to have a history of type III sarcoidosis and a chest x-ray consistent with
      aspergilloma. Bronchoscopy was performed within 48 hours from the onset of the
      patient's symptoms revealing generalized heme in both the left and right main
      bronchi. Massive hemoptysis is a potentially life-threatening complication from a
      variety of diseases. This case serves to illustrate the diagnostic considerations
      and potential therapeutic interventions in patients with advanced sarcoidosis.

PMID- 23168519
TI  - A case of endobronchial leiomyoma and carcinoma in situ treated with
      electrocautery using flexible bronchoscopy.
AB  - An 82-year-old woman presented with dyspnea, fever, cough, and an endobronchial
      mass in the right main stem bronchus. Initial bronchoscopy revealed 80%
      obstruction of the distal right main bronchus by an exophytic tumor mass.
      Endobronchial biopsy of the mass revealed squamous cell carcinoma in situ. A
      repeat flexible bronchoscopy was performed to obtain a deeper biopsy for
      definitive diagnosis and to relieve the obstruction. A hot forceps biopsy using
      electrocautery (20 W) was performed; no significant bleeding was encountered. A
      less vascular tumor was suspected because of the minimal bleeding, which led to
      the decision to ablate and excise the entire mass using electrocautery. The hot
      forceps biopsy of the endobronchial lesion revealed leiomyoma and no further
      evidence of carcinoma in situ. Follow-up bronchoscopy at 3 and 6 months showed no
      recurrence. Flexible bronchoscopy with electrocautery spared an elderly patient
      from a higher risk procedure and general anesthesia. This approach may be
      considered as an option for high-risk patients with vascular lesions.

PMID- 23168520
TI  - Technical advances: measurement of collateral flow in the lung with a dedicated
      endobronchial catheter system.
AB  - Interest in assessment of collateral flow measurement has resurfaced with the
      advent of endoscopic lung volume reduction studies, namely valve technologies (eg
      Emphasys EBV), that achieve volume reduction through lobar isolation. It is
      currently thought that collateral ventilation could be a contributing factor for
      endoscopic lung volume reduction failures, as isolated lobes can "backfill"
      through these channels. In an attempt to quantify collateral ventilation, the
      Chartis System has been developed by Pulmonx, Inc. to measure pressure and flow,
      and calculate resistance to airflow through collateral channels in isolated lung
      compartments.

PMID- 23168524
TI  - Age-related differences in abdominal fat distribution in premenopausal and
      postmenopausal women with cardiovascular disease.
AB  - OBJECTIVE: The aim of this study was to determine the effect of sex and the
      menopausal transition on age-related differences in visceral adipose tissue (VAT)
      and subcutaneous adipose tissue (SAT) among patients with cardiovascular disease.
      METHODS: A cross-sectional study of 997 women and 3,409 men with cardiovascular
      disease was performed. VAT and SAT were measured by ultrasonography. Differences
      in abdominal fat per decade in premenopausal and postmenopausal women were
      analyzed with linear regression and compared with men younger and older than the
      mean menopause age of women. RESULTS: VAT increased gradually across advancing
      age groups. For postmenopausal women, the 10-year differences in VAT were smaller
      than those for premenopausal women (0.24 cm [beta = 0.24; 95% CI, 0.05 to 0.43]
      vs 0.71 cm [beta = 0.71; 95% CI, 0.29 to 1.12]). There were no differences in SAT
      (beta = -0.12; 95% CI, -0.37 to 0.13) in premenopausal women, and SAT decreased
      across the age groups of postmenopausal women (-0.36 cm per decade [beta = -0.36;
      95% CI, -0.47 to -0.26]). Postmenopausal women showed 10-year differences in VAT
      that were larger than those for men 48 years or older (0.24 cm per decade [beta =
      0.24; 95% CI, 0.05 to 0.43] vs -0.01 cm per decade [beta = -0.01; 95% CI, -0.12
      to 0.10]). In addition, 10-year differences in SAT were larger in postmenopausal
      women than in men 48 years or older (-0.36 cm [beta = -0.36; 95% CI, -0.47 to 
      0.26] vs -0.22 cm [beta = -0.22; 95% CI, -0.27 to -0.18]). CONCLUSIONS: Menopause
      is not associated with accelerated fat gain in women with cardiovascular disease.
      Compared with similar-aged men, postmenopausal women show a steeper increase in
      VAT and a steeper decrease in SAT. These ongoing changes might add to an
      unfavorable metabolic profile associated with an increased risk of recurrent
      cardiovascular events.

PMID- 23168523
TI  - Reductions in glucose among postmenopausal women who use and do not use estrogen
      therapy.
AB  - OBJECTIVE: Among postmenopausal women who do not use estrogen therapy (ET), we
      have previously reported that intensive lifestyle modification (ILS) leads to
      increases in sex hormone-binding globulin (SHBG) and that such increases are
      associated with reductions in fasting plasma glucose (FPG) and 2-hour
      postchallenge glucose (2HG). Oral ET decreases FPG and increases 2HG while
      increasing both SHBG and estradiol (E2). It is unknown if ILS reduces glucose
      among ET users, if changes in SHBG and E2 might mediate any glucose decreases in
      ET users, and if these patterns differ from those in non-ET users. METHODS: We
      conducted a secondary analysis of postmenopausal women in the Diabetes Prevention
      Program who used ET at baseline and 1-year follow-up (n = 324) and who did not
      use ET at either time point (n = 382). Participants were randomized to ILS,
      metformin, or placebo administered at 850 mg BID. RESULTS: ET users were younger,
      more often white, and more likely to have had bilateral oophorectomy than non-ET
      users. Among ET users, ILS reduced FPG (P < 0.01) and 2HG (P < 0.01), and
      metformin reduced FPG (P < 0.01) but not 2HG (P = 0.56), compared with placebo.
      Associations between SHBG and total E2 with FPG and 2HG were not significant
      among women randomized to ILS or metformin. These patterns differed from those
      observed among women who did not use ET. CONCLUSIONS: We conclude that among
      glucose-intolerant ET users, interventions to reduce glucose are effective but
      possibly mediated through different pathways than among women who do not use ET.

PMID- 23168526
TI  - Distal acquired demyelinating symmetric polyneuropathy progressing to classic
      chronic inflammatory demyelinating polyneuropathy and response to fludarabine and
      cyclophosphamide.
AB  - INTRODUCTION: Distal acquired demyelinating symmetric polyneuropathy (DADS) is
      proposed as a distinct entity from classic chronic inflammatory demyelinating
      polyneuropathy (CIDP). METHODS: We report a 58-year-old woman with DADS that
      progressed to a severe case of classic CIDP. RESULTS: She had distal numbness and
      paresthesias, minimal distal weakness and impaired vibratory sensation. She had
      anti-MAG antibodies, negative Western blot, and lacked a monoclonal gammopathy.
      There were prolonged distal motor latencies. She remained stable for 6 years
      until developing proximal and distal weakness. Nerve conduction studies showed
      multiple conduction blocks. She developed quadriparesis despite first-line
      treatment for CIDP. She was started on cyclophosphamide and fludarabine. Twenty
      five months after receiving chemotherapy, she had only mild signs of neuropathy
      off all immunotherapy. CONCLUSIONS: DADS may progress to classic CIDP and is
      unlikely to be a separate disorder. Fludarabine and cyclophosphamide may be
      effective for refractory CIDP.

PMID- 23168527
TI  - Abdominal obesity and mortality: The Pennington Center Longitudinal Study.
AB  - The purpose of this study was to determine the association between visceral
      adipose tissue (VAT) and all-cause mortality. The sample included 1089 white men
      and women 18-84 years of age from the Pennington Center Longitudinal Study, a
      prospective cohort of participants assessed between 1995 and 2008, and followed
      for mortality until 31 December 2009. Abdominal VAT was measured at the L4-L5
      vertebral level using computed tomography. There were 27 deaths during an average
      of 9.1 years of follow-up. Abdominal VAT was significantly associated with
      mortality after adjustment for age, sex and year of examination (hazards ratio
      (HR) 1.46; 95% confidence interval 1.05-2.05). The association was stronger after
      the inclusion of abdominal subcutaneous adipose tissue (SAT), smoking status,
      alcohol consumption and leisure-time physical activity as additional covariates
      (HR 1.74; 1.17-2.59). Limiting the sample to participants who were free of
      stroke, heart disease and cancer at baseline reduced the strength of the
      relationship slightly (HR 1.62; 1.07-2.47). Abdominal SAT was not associated with
      mortality, either alone or in combination with VAT and other covariates. The
      results support the assertion that abdominal VAT is an important therapeutic
      target for obesity reduction efforts.

PMID- 23168528
TI  - Mrp1 is essential for sphingolipid signaling to p-glycoprotein in mouse blood
      brain and blood-spinal cord barriers.
AB  - At the blood-brain and blood-spinal cord barriers, P-glycoprotein, an ATP-driven
      drug efflux pump, is a major obstacle to central nervous system (CNS)
      pharmacotherapy. Recently, we showed that signaling through tumor necrosis factor
      alpha (TNF-alpha), sphingolipids, and sphingosine-1-phosphate receptor 1 (S1PR1)
      rapidly and reversibly reduced basal P-glycoprotein transport activity in the rat
      blood-brain barrier. The present study extends those findings to the mouse blood
      brain and blood-spinal cord barriers and, importantly, identifies multidrug
      resistance-associated protein 1 (Mrp1, Abcc1) as the transporter that mediates
      S1P efflux from brain and spinal cord endothelial cells. In brain and spinal cord
      capillaries isolated from wild-type mice, TNF-alpha, sphingosine, S1P, the S1PR
      agonist fingolimod (FTY720), and its active, phosphorylated metabolite, FTY720P,
      reduced P-glycoprotein transport activity; these effects were abolished by a
      specific S1PR1 antagonist. In brain and spinal cord capillaries isolated from
      Mrp1-null mice, neither TNF-alpha nor sphingosine nor FTY720 reduced P
      glycoprotein transport activity. However, S1P and FTY720P had the same S1PR1
      dependent effects on transport activity as in capillaries from wild-type mice.
      Thus, deletion of Mrp1 alone terminated endogenous signaling to S1PR1. These
      results identify Mrp1 as the transporter essential for S1P efflux from the
      endothelial cells and thus for inside-out S1P signaling to P-glycoprotein at the
      blood-brain and blood-spinal cord barriers.

PMID- 23168529
TI  - Brain magnetic resonance spectroscopy in episodic hepatic encephalopathy.
AB  - Brain magnetic resonance (MR) study has shown metabolic abnormalities and changes
      in water distribution of the brain tissue that may relate to the pathogenesis of
      hepatic encephalopathy (HE). We designed a study to investigate the disturbances
      in brain water and metabolites during episodic HE using a 3-T MR scanner.
      Cirrhotic patients with different grades of HE underwent MR during
      hospitalization (n=18). The MR was repeated at 6 weeks' follow-up (n=14). The
      results were compared with those of a group of healthy volunteers (n=8). During
      episodic HE, brain diffusion-weighted imaging showed a high apparent diffusion
      coefficient (ADC) (12% to 14%) that decreased during follow-up (-1% to -4%).
      These disturbances were accompanied by high glutamine (581%), low choline (-31%),
      and low myo-inositol (-86%) peaks on MR spectroscopy. In overt HE, patients
      showed high glutamine that decreased during follow-up (-22%). In addition, these
      patients exhibited a rise in plasma S100 beta and enlargement of brain white
      matter lesions. In conclusion, several disturbances detected by MR support the
      presence of impaired brain water homeostasis during episodic HE. Although
      astrocytes have a major role in this condition, brain edema during episodic HE
      may be extracellular and does not appear to be directly responsible for the
      development of neurologic manifestations.

PMID- 23168530
TI  - Purinergic receptors regulate myogenic tone in cerebral parenchymal arterioles.
AB  - Myogenic tone is a fundamental aspect of vascular behavior in resistance
      arteries. This contractile response to changes in intravascular pressure is
      critically involved in blood flow autoregulation in tissues such as the brain,
      kidneys, and heart. Myogenic tone also helps regulate precapillary pressure and
      provides a level of background tone upon which vasodilator stimuli act to
      increase tissue perfusion when appropriate. Despite the importance of these
      processes in the brain, little is known about the mechanisms involved in control
      of myogenic tone in the cerebral microcirculation. Here, we report that
      pharmacological inhibition of P2Y4 and P2Y6 pyrimidine receptors nearly abolished
      myogenic tone in cerebral parenchymal arterioles (PAs). Molecular suppression of
      either P2Y4 or P2Y6 receptors using antisense oligodeoxynucleotides reduced
      myogenic tone by 44%+/-8% and 45%+/-7%, respectively. These results indicate that
      both receptor isoforms are activated by increased intravascular pressure, which
      enhances the activity of voltage-dependent calcium channels and increases
      myogenic tone in PAs. Enhancement or inhibition of ectonucleotidase activity had
      no effect on parenchymal arteriolar myogenic tone, indicating that this response
      is not mediated by local release of nucleotides, but rather may involve direct
      mechanical activation of P2Y receptors in the smooth muscle cells.

PMID- 23168531
TI  - Measuring biexponential transverse relaxation of the ASL signal at 9.4 T to
      estimate arterial oxygen saturation and the time of exchange of labeled blood
      water into cortical brain tissue.
AB  - The transverse decay of the arterial spin labeling (ASL) signal was measured at
      four inflow times in the rat brain cortex at 9.4 T. Biexponential T2 decay was
      observed that appears to derive from different T2 values associated with labeled
      water in the intravasculature (IV) and extravascular (EV) compartments. A two
      compartment biexponential model was used to assess the relative contribution of
      the IV and EV compartments to the ASL signal, without assuming a value for T2 of
      labeled blood water in the vessels. This novel methodology was applied to
      estimate the exchange time of blood water into EV tissue space and the oxygen
      saturation of blood on the arterial side of the vasculature. The mean exchange
      time of labeled blood water was estimated to be 370+/-40 ms. The oxygen
      saturation of the arterial side of the vasculature was significantly less than
      100% (~85%), which may have implications for quantitative functional magnetic
      resonance imaging studies where the arterial oxygen saturation is frequently
      assumed to be 100%.

PMID- 23168532
TI  - Oxygen consumption rates during three different neuronal activity states in the
      hippocampal CA3 network.
AB  - The brain is an organ with high metabolic rate. However, little is known about
      energy utilization during different activity states of neuronal networks. We
      addressed this issue in area CA3 of hippocampal slice cultures under well-defined
      recording conditions using a 20% O(2) gas mixture. We combined recordings of
      local field potential and interstitial partial oxygen pressure (pO(2)) during
      three different activity states, namely fast network oscillations in the gamma
      frequency band (30 to 100 Hz), spontaneous network activity and absence of
      spiking (action potentials). Oxygen consumption rates were determined by pO(2)
      depth profiles with high spatial resolution and a mathematical model that
      considers convective transport, diffusion, and activity-dependent consumption of
      oxygen. We show that: (1) Relative oxygen consumption rate during cholinergic
      gamma oscillations was 2.2-fold and 5.3-fold higher compared with spontaneous
      activity and absence of spiking, respectively. (2) Gamma oscillations were
      associated with a similar large decrease in pO(2) as observed previously with a
      95% O(2) gas mixture. (3) Sufficient oxygenation during fast network oscillations
      in vivo is ensured by the calculated critical radius of 30 to 40 MUm around a
      capillary. We conclude that the structural and biophysical features of brain
      tissue permit variations in local oxygen consumption by a factor of about five.

PMID- 23168533
TI  - Risk factors for direct heat-related hospitalization during the 2009 Adelaide
      heatwave: a case crossover study.
AB  - Adelaide experienced an extreme and prolonged 13 days heatwave in summer 2009.
      The health impacts of this heatwave included an almost 14-fold increase in direct
      heat-related hospital admissions. This study aims to investigate the risk factors
      for this extra health burden. A case crossover study was conducted in
      metropolitan Adelaide to compare the characteristics of patients from the
      heatwave (exposure) period and non-heatwave (control) periods before and after.
      Direct heat-related hospitalizations were identified based on the ICD-10 codes
      (X30, T67, and E86). Patients' data, including age, gender, indicators of health
      status, living conditions and socio-economic status, were collected from the
      South Australian Department of Health and patients' case-notes from seven major
      Adelaide hospitals. Multivariate logistic regression model was used to estimate
      the odd ratios (OR) and the 95% confidence intervals (CI). Results indicate that
      living at residential aged care (OR=0.41, 95% CI: 0.15-0.70) and having higher
      number of co-morbidities (OR=0.89, 95% CI: 0.83-0.95) reduced the risk of
      hospital admission for direct heat-related illnesses during the heatwave, while
      having renal problems (OR=1.72, 95% CI: 1.07-2.94), reporting a fall prior to
      hospitalization (OR=2.04, 95% CI: 1.10-3.77), receiving assistance from community
      (OR=2.31, 95% CI: 1.24-4.30), living alone (OR=2.41, 95% CI: 1.32-4.40), socio
      economic disadvantage (OR=2.10, 95% CI: 1.09-4.04) and no private health
      insurance (OR=1.82, 95% CI: 1.05-3.16) increased the risk. In conclusion, the
      people most at risk during the 2009 heatwave in Adelaide were those who lived
      alone, received help from community services, with co-existing renal problems or
      a risk of falls, and with a lower socio-economic status. Findings will assist in
      refining heat-health response systems and developing intervention programmes.

PMID- 23168534
TI  - Using imaging-based, three-dimensional models of the cervix and uterus for
      studies of cervical changes during pregnancy.
AB  - Preterm birth affects over 12% of all pregnancies in the United States for an
      annual healthcare cost of $26 billion. Preterm birth is a multifactorial disorder
      but cervical abnormalities are a prominent feature in many patients. Women with a
      short cervix are known to be at increased risk for preterm birth and a short
      cervix is used to target therapy to prevent preterm birth. Although the clinical
      significance of a short cervix is well known, the three-dimensional anatomical
      changes that lead to cervical shortening are poorly understood. Here, we review
      our previous studies of the three-dimensional anatomy of the cervix and uterus
      during pregnancy. The rationale for these studies was to improve our
      understanding of the deformation mechanisms leading to cervical shortening. Both
      magnetic resonance imaging and three-dimensional (3D) ultrasound were used to
      obtain anatomical data in healthy, pregnant volunteers. Solid models were
      constructed from the 3D imaging data. These solid models were used to create
      numerical models suitable for biomechanical simulation. Three simulations were
      studied: cervical funneling, uterine growth, and fundal pressure. These
      simulations showed that cervical changes are a complex function of the tissue
      properties of the cervical stroma, the loading conditions associated with
      pregnancy and the 3D anatomical geometry of the cervix and surrounding
      structures. An improved understanding of these cervical changes could point to
      new approaches to prevent undesired cervical shortening. This new insight should
      lead to therapeutic strategies to delay or prevent preterm birth.

PMID- 23168535
TI  - Sacral neuromodulation effects on periurethral sensation and urethral sphincter
      activity.
AB  - AIMS: To characterize the effect of sacral neuromodulation (SNM) on urethral
      neuromuscular function. METHODS: Following IRB approval, women with refractory
      overactive bladder (OAB) underwent standardized urethral testing prior to and
      after Stage 1 SNM implantation. Periurethral sensation was measured using current
      perception thresholds (CPT). Striated urethral sphincter activity was quantified
      using concentric needle electromyography (CNE) and Multi-Motor Unit Action
      Potential (MUP) analysis software. Nonparametric analyses were used to
      characterize pre/post changes with intervention. Baseline CPT and CNE findings
      were compared between SNM responders and non-responders. RESULTS: Twenty-seven
      women were enrolled in this pilot study with a mean age of 61 +/- 13 years.
      Twenty of 26 women (76.9%) responded to SNM and went to Stage 2 permanent
      implantation. Four (14.8%) withdrew after Stage 1 implantation; three of the four
      withdrawals had not had therapeutic responses to SNM. CPT and CNE parameters did
      not significantly differ from baseline 2 weeks after SNM. Pre-SNM urethral
      sensation was not significantly different between responders and non-responders.
      However, responders had larger amplitude, longer duration and more turns and
      phases at baseline approaching significance, reflecting more successful urethral
      reinnervation, than non-responders. CONCLUSIONS: SNM does not alter urethral
      neuromuscular function 2 weeks post Stage 1 implantation.

PMID- 23168536
TI  - Rational design of Hg2+ controlled streptavidin-binding aptamer.
AB  - Through substituting two canonical base pairs of a streptavidin-binding aptamer
      with T-T mismatched base pairs, a new aptamer was constructed. Its binding
      ability could be controlled by Hg(2+) through the formation of T-Hg-T metal-base
      pairs.

PMID- 23168537
TI  - Systems pharmacology uncovers Janus functions of botanical drugs: activation of
      host defense system and inhibition of influenza virus replication.
AB  - Given the imminent threat of influenza pandemics and continuing emergence of new
      drug-resistant influenza virus strains, novel strategies for preventing and
      treating influenza disease are urgently needed. Herbal medicine, used for
      thousands of years in combinational therapies (Herb Formula), plays a significant
      role in stimulating the host immune system in vivo, and meanwhile, in fighting
      against the pandemic by directly inhibiting influenza virus in vitro. Such
      potential Janus functions may spark interest in therapeutic manipulation of virus
      diseases. Unfortunately, the molecular mechanism of the Janus functions of the
      medicinal herbs in the treatment of influenza remains unclear. In this work, to
      illustrate the therapeutic concept of Janus functions in the treatment of
      influenza, we have introduced a novel systems pharmacology model that integrates
      pharmacokinetic screening, targeting and network analysis of two representative
      herbs Lonicera japonica and Fructus Forsythiae that are efficient in the
      treatment of influenza, inflammation and other diseases. 50 Chemicals with
      favorable pharmacokinetic profiles have been identified for the two herbs, and
      the ligand-target network was constructed by complementing the literature-based
      experimental data deposited in DrugBank. The annotation of these chemicals was
      assigned using a novel drug targeting approach, and mapped to target-disease and
      drug-target-pathway networks. The overall data suggest that the medicinal herbs
      function by indirectly suppressing the virus proliferation via regulating the
      immune systems in hosts, and also, by directly inhibiting virus proliferation
      through targeting viral proteins essential for the viral life cycle. For the
      first time, we have demonstrated the mechanism of medicinal herbs in prevention
      and treatment of virus diseases via the Janus functions on a systematic level.

PMID- 23168539
TI  - Photo-induced cation exchange reaction of germanium chalcogenide nanocrystals
      synthesized using gas-phase laser photolysis reaction.
AB  - Germanium chalcogenide GeS(x)Se(1-x) nanocrystals (NC) were synthesized using a
      novel gas-phase laser photolysis reaction. The composition was simply controlled
      by the partial pressure of precursors in a closed reactor. Remarkably, these
      ligand-free NC undergo the photo-induced cation exchange reaction to produce a
      series of Cd, Zn, Pb, and Ag chalcogenide NC in aqueous solution, which is
      governed by the thermodynamic driving force based on solubility.

PMID- 23168542
TI  - Transbronchial needle forceps: are needles not enough?

PMID- 23168543
TI  - Improving the specificity of autofluorescence bronchoscopy.

PMID- 23168544
TI  - Endobronchial cancer detection using an integrated bronchoscopy system for
      simultaneous imaging and noncontact spectral measurement.
AB  - INTRODUCTION: Quantitative spectroscopy has been proposed as a means of improving
      the specificity of autofluorescence bronchoscopy by discriminating between true
      malignancy and suspicious but benign lesions before biopsy. This study
      investigated the potential discrimination ability of microvascular tissue-related
      parameters and relative intensity of autofluorescence, as estimated by noncontact
      spectroscopy. METHODS: Patients undergoing bronchoscopy for suspicion of lung
      cancer were enrolled from 4 sites (Canada, Russia, Slovenia, and the United
      Kingdom). In lesions selected for biopsy, light from a special fiberoptic
      bronchoscope was diverted to a spectrophotometer to obtain spectral measurements.
      The mucosa blood volume fraction and oxygen saturation were estimated from the
      computer model and, along with the autofluorescence intensity, were analyzed for
      discrimination potential for severe dysplasia or worse against lower histology
      grades. RESULTS: A total of 485 patients were enrolled, from whom 352 suspicious,
      adequate biopsy specimens were collected. Of these, 8 specimens were severe
      dysplasia or carcinoma in situ, and 66 were cancer. All measures were found to be
      significantly altered (receiver operating characteristic curve area: 0.83, 0.74,
      and 0.80 for autofluorescence intensity, the blood volume fraction, and oxygen
      saturation, respectively) in lesions found by biopsy to have severe dysplasia or
      higher grade present. In addition, the estimated volume fraction of desaturated
      blood was found to be significantly more discriminatory than that of oxygen
      saturated blood (receiver operating characteristic curve area: 0.83 vs. 0.63).
      Study center differences were evident and suggest that results may depend on
      study population or bronchoscopist experience. CONCLUSIONS: Noncontact
      measurement and estimation of the above microvascular-related parameters,
      obtained during regular bronchoscope examination, may have potential for
      improving discrimination of severe dysplasia and cancer in lesions suspicious
      under white light bronchoscopy/autofluorescence bronchoscopy.

PMID- 23168545
TI  - Endobronchial Ultrasound-guided Transbronchial Miniforceps Biopsy of Mediastinal
      and Hilar Lymph Node Stations.
AB  - Linear array endobronchial ultrasound has significantly improved the diagnostic
      yield of transbronchial needle aspiration for the diagnosis of centrally located
      lesions within the thorax. Although transbronchial needle aspiration has become
      an accepted technique for diagnosing solid tumors within the chest, its yield for
      hematologic malignancies such as lymphoma and other benign conditions in which
      direct examination of tissue architecture are preferred is lower. Currently,
      surgical biopsies by mediastinoscopy or video-assisted thoracic surgery are often
      required to obtain adequate tissue specimens to make these diagnoses. In this
      retrospective study, we review our experience with patients who underwent
      endobronchial ultrasound-guided miniforceps biopsy of abnormalities at
      mediastinal and hilar lymph node stations.

PMID- 23168546
TI  - Bronchoscopy in pulmonary hydatidosis: retrospective analysis.
AB  - The diagnosis of unruptured pulmonary hydatidosis is based on classical
      radiologic features. However, ruptured or complicated hydatid cysts alter the
      radiologic signs and lead to delayed or incorrect diagnosis. The role of flexible
      bronchoscopy was assessed as a diagnostic tool in the evaluation in such cases.
      Between 2002 and 2008, 14 patients (7 female, 7 male), aged between 18 and 55
      years, with a mean age of 36 years, were evaluated for pulmonary hydatidosis.
      Clinical history, radiologic findings, and other investigations of the patients
      were reviewed retrospectively at a tertiary referral center. All 14 patients were
      symptomatic, with cough, hemoptysis, and chest pain being the most common
      symptoms. Seven patients had right lung involvement, whereas 6 patients had left
      sided predilection, and the remainder presented with pleural disease. At flexible
      bronchoscopy, white glistening membrane could be observed in 9 patients, whereas
      cytologic evaluation of bronchial washing did not show cuticular particles,
      degenerated scoleces, or hooklets in any of the cases. Twelve patients underwent
      uneventful surgical intervention. Surgical specimens showed 2 unruptured
      pulmonary hydatid cysts (uncomplicated), 1 pleural hydatid, and 9 ruptured
      pulmonary hydatid cysts. Of the 9 ruptured hydatid cyst cases, evidence of fungal
      (aspergillus) colonization, bacterial infection, and coexistent tuberculous
      granuloma was reported in 2 cases each. Bronchoscopy is an important tool that
      aids in confirming the diagnosis before surgery, especially in complicated
      pulmonary hydatidosis. Special stains for cytologic specimen should be used if
      the possibility of ruptured hydatid is thought to improve the diagnostic yield.
      The histopathology of the surgical specimen should be reviewed for associated
      secondary infection and fungal colonization.

PMID- 23168547
TI  - Assessment of patient satisfaction and lidocaine requirement during flexible
      bronchoscopy without sedation.
AB  - BACKGROUND: Bronchoscopy is usually performed under sedation to improve patient
      comfort and willingness to accept a repeat procedure. Bronchoscopy with a low
      dose of sedation does not necessarily improve patient comfort, and overt sedation
      may be dangerous for those with preexisting lung diseases. OBJECTIVES: The aim of
      this study was to evaluate the visual analogue scale for cough, pain, nausea,
      choking sensation, and overall discomfort level during flexible bronchoscopy
      without sedation. Acceptance of repeat bronchoscopy and requirement of lidocaine
      during the procedure were also evaluated. METHODS: We evaluated 70 consecutive
      patients who underwent flexible bronchoscopy without sedation at our hospital.
      None received any premedication, and lidocaine was used as a topical anesthetic
      during the procedure. After the bronchoscopy, a questionnaire containing the
      visual analogue scale for cough, pain, nausea, choking sensation, and overall
      discomfort during the procedure was administered. Total requirement of lidocaine
      and patients' willingness to return for repeat bronchoscopy were recorded.
      RESULTS: Visual analogue scale ratings of cough, pain, nausea, and choking
      sensation during the study procedure were mild to moderate in 38.6% to 94.3% of
      the patients. The mean dose of lidocaine used during the bronchoscopy was 7.44+/
      2.09 mg/kg. The visual analogue scale of any symptom score had no correlation
      with the amount of lidocaine used (P>0.05). Only 27.1% would definitely accept
      repeat bronchoscopy, if required. CONCLUSIONS: Bronchoscopy without sedation is
      quite a well-tolerated procedure, and the required amount of lidocaine during the
      procedure does not exceed the recommended dose. However, acceptance of repeat
      bronchoscopy is low.

PMID- 23168548
TI  - Clinical experience of removing dentures from aerodigestive tract.
AB  - OBJECTIVE: A denture as an aerodigestive tract foreign body continues to present
      challenges to otolaryngologists. Records of patients who presented with a denture
      as an aerodigestive tract foreign body were retrospectively reviewed. METHODS:
      Records of patients treated during the last 8 years were reviewed to gather
      information on the age, sex, and presenting symptoms of the patient, location of
      the denture, radiographic findings, and endoscopic procedure required. RESULTS:
      Our review identified 15 patients, with the mean and median age being 59.6 and 63
      years, respectively. One patient presented with a denture in the valleculae, 4
      patients with a denture in the airway, and 10 patients with a denture in the
      hypopharynx/esophagus. Rigid endoscopy was performed to remove the dentures in
      most patients. An esophagotomy was required in 1 patient. CONCLUSIONS: Fixed
      partial dentures should be advised by dentists, especially in patients who have
      predisposing factors such as old age, epilepsy, mental retardation, or
      alcoholism.

PMID- 23168549
TI  - Pilot feasibility study of transbronchial needle forceps: a new tool for
      obtaining histology samples from mediastinal subcarinal lymph nodes.
AB  - BACKGROUND: Cutting transbronchial histology needles to obtain tissue cores from
      hilar/mediastinal lymph nodes or masses adjacent to the tracheobronchial tree are
      able to provide adequate histology tissue samples in only 38% to 78% of cases.
      The aim of this pilot study was to evaluate the efficacy and safety of a new
      instrument developed to obtain a fragment of a tissue for histologic diagnosis of
      enlarged subcarinal lymph nodes. METHODS: The transbronchial needle forceps
      (TBNF) is a sampling instrument that combines the characteristics of a needle
      (beveled tip for penetrating through the bronchial wall) with that of a forceps
      (2 serrated jaws for grasping the biopsy). The external diameter of the needle
      forceps is 1.5 mm. RESULTS: Fourteen patients (11 male, 3 female; mean age: 51 y)
      with subcarinal lymph node enlargement greater than 2 cm in short axis were
      included in this pilot study. TBNF provided tissue for histologic diagnosis in 8
      patients (57.1%). In 4 patients (28.5%) TBNF could not be inserted through the
      bronchial wall. For patients in whom it was possible to insert the TBNF, a tissue
      core adequate for histologic examination was obtained in 9 (90%) and a diagnosis
      in 8 (80%) (non-small-cell lung cancer in 3, sarcoidosis in 2, small cell lung
      cancer in 1, tuberculosis in 1, and Hodgkin lymphoma in 1). No clinically
      significant procedure-related complications were encountered. CONCLUSIONS: This
      study demonstrates that, when insertion through the bronchial wall is possible,
      TBNF safely provides diagnostic histologic specimens of subcarinal
      lymphadenopathy in a large percentage of cases.

PMID- 23168550
TI  - Respiratory arrest caused by endobronchial sclerosing hemangioma of the left main
      bronchus.
AB  - Sclerosing hemangioma is a rare pulmonary tumor that usually grows as a
      peripheral intraparenchymal lesion in the lungs. Although some case series have
      described this rare tumor, endobronchial growth of sclerosing hemangioma is
      extremely rare, with only 3 reported cases in the literature to date. We describe
      a patient who presented with respiratory arrest secondary to bilateral mechanical
      airway obstruction caused by this tumor. Such a presentation has never been
      described in the literature before and, as such, proved to be a challenging
      diagnosis.

PMID- 23168551
TI  - Tracheostomy Tube-induced Tracheoesophageal Fistula.
AB  - Tracheostomy is one of the most common elective surgical procedures performed in
      critically ill patients. The complications of tracheostomy may be categorized on
      the basis of duration from the procedure: early-intraoperative, medium-early
      postoperative, and late postoperative. Tracheoeosphageal fistula is one of the
      known late complications of tracheostomy. Injury to the tracheal wall can occur
      because of high cuff pressure or direct mechanical trauma from the tracheostomy
      tube. We report a case of tracheoeosphageal fistula caused by a cuffless
      tracheostomy tube that was managed by an endobronchial stent.

PMID- 23168552
TI  - Pneumomediastinum complicating transbronchial needle aspiration.
AB  - Transbronchial needle aspiration (TBNA) is a safe procedure with a reported
      complication rate of less than 1%. Pneumomediastinum after TBNA has not been
      reported in the English literature in the past. We present the case of a 65-year
      old woman with widely metastatic small cell carcinoma, who developed
      pneumomediastinum after flexible bronchoscopy with TBNA. A persistent visible
      defect in the bronchial wall at the site of the needle insertion strongly
      implicated the TBNA as the cause of the pneumomediastinum.

PMID- 23168553
TI  - Successful treatment of endobronchial carcinoid using argon plasma coagulation.
AB  - Bronchial carcinoids are rare, well-differentiated, neuroendocrine malignant
      tumors and account for 5% of all lung neoplasms. The standard of care for the
      carcinoid tumors has been surgical resection. Various interventional
      bronchoscopic techniques are available for the treatment of intraluminal
      carcinoid. One of these new techniques with less complication is argon plasma
      coagulation. In this study, we report a case of huge endobronchial carcinoid
      tumor referred to us from the thoracic surgery ward, which was not surgically
      resectable. The tumor was treated successfully with argon plasma coagulation.

PMID- 23168554
TI  - Radiofrequency ablation for inoperable lung cancer: a case report.
AB  - Lung cancer is among the most common malignancies in the world. Optimal
      treatments for unresectable primary lung cancer, local recurrence of lung cancer
      within a previous radiation field, pulmonary metastases, and small lung cancers
      (1 cm) have not been found. Radiofrequency ablation (RFA) has been increasingly
      performed as a local treatment for lung malignancies. Herein, we present a case
      of inoperable lung cancer that was successfully treated with a combination of RFA
      and radiotherapy. A 69-year-old man presented with exertion dyspnea of 3 weeks'
      duration. He had a remote history of larynx and lung cancer. The patient had
      remained in remission for 14 years until the current presentation. On physical
      examination, the patient was not in acute distress, and chest sounds were normal
      except for minimal prolongation of expiration. On a thorax computed tomography
      (CT) scan, a 2.3*1.7-cm, ill-defined, cystic lesion in the left upper lobe
      adjacent to major fissure was detected. CT-guided transthoracic fine needle
      aspiration biopsy revealed adenocarcinoma but the procedure was complicated by
      pneumothorax and hypercapnic respiratory failure. On account of the emerging
      medical inoperability, radiation therapy at 45 Gy in 3 fractions and RFA were
      performed successfully. After the ninth month of treatment, no fluorodeoxyglucose
      uptake was detected in the RFA application site in the control positron emission
      tomography-CT images (complete remission). RFA is a newer technique for lung
      cancer. Although the results of most studies were short and mid term, for
      patients with poor lung functions, RFA is an encouraging treatment modality,
      especially when combined with radiotherapy or chemotherapy in the presence of
      appropriate patient selection, adequate equipment, and experienced staff.

PMID- 23168555
TI  - An unusual case of hurthle cell carcinoma presenting as metastatic pleural
      disease 16 years after thyroidectomy.
AB  - BACKGROUND: Hurthle cell carcinoma (HCC), a variant of a follicular carcinoma of
      the thyroid, is an aggressive type of differentiated thyroid cancer now
      considered a distinct pathologic entity. It may present as a low-grade tumor or
      as a more aggressive type. Prognosis depends on the age of the patient, tumor
      size, extent of invasion, and initial nodal or distant metastasis. Although
      thoracic involvement is not unusual with this tumor, this is the first report, to
      our knowledge, of latent pleural and lung metastases that were detected by a
      thoracentesis. PATIENT AND METHODS: A 63-year-old woman underwent total
      thyroidectomy for a thyroid mass in 1990 that was diagnosed as HCC. In December
      2006, she presented with symptoms of dyspnea and an abnormal chest x-ray. A
      subsequent ultrasound-guided thoracentesis revealed a malignant, exudative
      effusion. Cytopathologic analysis revealed the malignancy to be consistent with
      HCC. She was reevaluated by her original oncologist and is undergoing treatment
      for metastatic HCC. CONCLUSIONS: Although rare, HCC may present years after
      definitive therapy as metastatic pleural and lung disease. Further studies are
      needed to determine the cause of latency in such cases.

PMID- 23168556
TI  - Diagnosis of Mesothelioma Using Flexible Bronchoscopy With Endobronchial
      Ultrasound-guided Biopsy of Mediastinal Lymph Nodes.
AB  - Malignant mesothelioma is a neoplasm that can arise from the mesothelial surface
      of the pleura and tends to be locally invasive. Various techniques have been used
      for diagnosis and include thoracentesis with pleural fluid cytology, closed
      pleural biopsy, and video-assisted thoracoscopic surgery. Thoracentesis and
      closed pleural biopsy can often establish the presence of malignancy, but
      frequently do not provide sufficient tissue to definitively diagnose malignant
      mesothelioma. Video-assisted thoracoscopic surgery biopsy has higher sensitivity
      for establishing the diagnosis, but is a more invasive procedure and is usually
      performed under general anesthesia. We discuss 2 cases in which the diagnosis of
      malignant pleural mesothelioma was made through flexible fiberoptic bronchoscopy
      with endobronchial ultrasound-guided mediastinal lymph node biopsy. We suggest
      that this technique provides a relatively noninvasive means for earlier
      definitive diagnosis of malignant mesothelioma when chest imaging demonstrates
      mediastinal lymphadenopathy.

PMID- 23168557
TI  - Spontaneous reexpansion of lung tissue after chronic atelectasis due to a
      stenotic airway.
AB  - Chronic atelectasis is a commonly reported complication of bronchial stenosis and
      airway obstruction. Bronchial stenosis after aspiration of oral medications has
      been reported in the literature many times. Spontaneous reexpansion of lung
      tissue after chronic atelectasis due to a stenotic airway is an unusual and
      unreported phenomenon. We present the case of a 72-year-old woman with documented
      history of chronic left lower lobe atelectasis due to bronchial stenosis from
      aspiration of an iron tablet 2 years before the current presentation. Two days
      after the initial aspiration event, a bronchoscopy was performed with the
      retrieval of an iron tablet from her left mainstem bronchus (LMB) using saline
      lavage and suctioning. This appeared successful at the time of the procedure.
      Repeat imaging of the chest and 2 diagnostic bronchoscopies over the following 2
      years revealed near-complete atelectasis of the left lung with occlusion of the
      LMB. In September 2008, she presented with worsening shortness of breath. On
      examination, she had absent breath sounds at the left lung base. A chest computed
      tomography scan revealed scarring of the LMB and left lower lobe atelectasis with
      improved aeration notable in parts of the lung previously documented to have
      collapsed. A bronchoscopy revealed an approximately 90% stenosis of the left
      mainstem LMB. Balloon dilation was performed; although there was significant
      bronchoscopic improvement noted, the patient did not report any relief of her
      symptoms from the procedure.

PMID- 23168558
TI  - Endobronchial instillations of amphotericin B: complementary treatment for
      pulmonary mucormycosis.
AB  - Pulmonary mucormycosis is a rare fungal infection that appears in patients with
      hematologic diseases who are immunosuppressed by chemotherapy. We report a case
      of pulmonary mucormycosis in a 21-year-old man with acute lymphoblastic
      leukaemia. During the period of pancytopenia he developed invasive mucormycosis.
      His initial symptoms were pleuritic chest pain with fever and unresponsiveness to
      broad-spectrum antibiotics. The outcome was favorable after long-term systemic
      and aerosolized amphotericin B, endobronchial instillations of amphotericin B,
      posaconazole, and surgery.

PMID- 23168559
TI  - Denture misadventure: an unusual cause of hemoptysis.
AB  - We report a case of a foreign body aspirated 9 years before presentation with
      hemoptysis. Chest radiographs failed to show 2 radiolucent denture palate
      fragments that ultimately were identified on computed tomography of the chest.
      After an unsuccessful flexible bronchoscopy, the foreign bodies were extracted
      using rigid bronchoscopy. Although rare, foreign body aspiration can be
      overlooked. Thus, it is important to maintain this diagnosis in the differential
      for patients with unexplained pulmonary symptoms.

PMID- 23168560
TI  - Endobronchial metastases from endometrial carcinoma.
AB  - A 78-year-old woman status post hysterectomy and radiation therapy 3 years
      earlier for endometrial carcinoma presented with cough, dyspnea, and weight loss.
      Computed tomography revealed left upper lobe atelectasis due to an obstructing
      endobronchial mass, enlarged mediastinal lymph nodes, a moderate left pleural
      effusion, and several subcentimeter nodules in the right lung. Flexible
      bronchoscopy confirmed a tumor mass obstructing the left upper lobe bronchus.
      Endobronchial biopsy revealed metastatic adenocarcinoma with histology similar to
      the previously resected endometrial primary and immunohistochemical staining
      consistent with endometrial carcinoma. To our knowledge, endobronchial metastases
      from endometrial carcinoma have been reported only once before.

PMID- 23168562
TI  - Management of intractable pneumothorax in the medically unfit.

PMID- 23168561
TI  - Endobronchial Stenosis due to Wegener Granulomatosis.
AB  - Wegener granulomatosis (WG) is characterized by a necrotizing granulomatous
      vasculitis. Computed tomography of the chest is effective in detecting lung
      involvement with pulmonary nodules with or without cavitations and airspace
      consolidation. We report a case of endobronchial stenoses in the setting of WG. A
      48-year-old man was admitted with complaints of dyspnea, cough, and sputum. A
      computed tomography scan revealed consolidation and small cavitating nodules, and
      stenoses were observed during bronchoscopy endobronchial. Narrowing improved
      after pulse cyclophosphamide and prednisolone therapy. Endobronchial stenoses are
      rare in the course of WG, and occur even more rarely than subglottic stenosis.
      Combined treatment with cytotoxic and corticosteroid agents has improved
      prognosis and long-term survival in patients with WG.

PMID- 23168563
TI  - Beta band patterns in the visible and masked sections of the coincidence
      anticipation timing task.
AB  - In this study, we examined beta band patterns during the coincidence-anticipation
      timing task. The tasks were the coincidence-anticipation timing task using a
      partially masked stimulus runway and a control task using the stimulus runway
      with no masking. Both tasks were displayed on a computer screen placed 1.3 m in
      front of the participants while they were seated in an armchair. Ten healthy
      right-handed adult men were asked to press a holding push button with their right
      thumb when a downward-moving visual target arrived at the end of each task. The
      electroencephalogram during both tasks was divided into three segments: the
      visible section, the first half of the masked section, and the second half of the
      masked section. The valid epochs were subjected to fast Fourier transform to
      obtain the power density in the beta bands. Power in the beta bands was expressed
      as a percentage of the total power (3-30 Hz) in each segment. The results showed
      that the percentage of beta band activity in Brodmann's areas 7 and 19 was
      significantly increased in both the visible and the masked sections of the
      coincidence-anticipation timing task compared with the control task. These
      results suggest that Brodmann's areas 7 and 19 mainly contribute toward attention
      to visual targets in the visible section and to movement prediction of moving
      visual targets in the masked section. In addition, Brodmann's areas 9 and 10,
      which were inactive, might affect the response time in the masked section during
      the coincidence-anticipation timing task.

PMID- 23168564
TI  - Magnetic resonance imaging of amyloid plaques using hollow manganese oxide
      nanoparticles conjugated with antibody abeta1-40 in a transgenic mouse model.
AB  - In this study, we have shown the feasibility of hollow manganese oxide
      nanoparticles (HMON) conjugated with an antibody of Abeta1-40 peptide (abAbeta40)
      (HMON-abAbeta40) for MRI of amyloid plaques in APP/PS1 transgenic mice. MR brain
      images in APP/PS1 transgenic mice and their nontransgenic littermates were
      acquired using a 7.0 T MRI system before, and 24 and 72 h after an injection of
      HMON-abAbeta40. After the injection of HMON-abAbeta40, we found hyperenhanced
      spots in the frontal cortex area on T1-weighted MR images for transgenic mice,
      which corresponded qualitatively to amyloid plaques detected by thioflavin-S
      staining. For quantitative analysis, percent MR signal changes in six brain
      regions (olfactory cortex, frontal cortex, cerebral cortex, thalamus,
      hippocampus, and cerebellar cortex) were compared between transgenic and wild
      type mice. We found significant increases in the percent MR signal changes in the
      olfactory cortex, frontal cortex, cerebral cortex, and hippocampus, but there
      were no significant differences in the thalamus and cerebellar cortex for
      transgenic mice compared with wild-type mice. This unique strategy allowed us to
      detect brain regions subjected to amyloid plaque deposition in Alzheimer's
      disease transgenic mouse models and has a potential to be developed for human
      applications, which has a current utility in preclinical research, particularly
      in monitoring therapeutic response for drug development in Alzheimer's disease.

PMID- 23168565
TI  - Thrombin induces release of proinflammatory chemokines interleukin-8 and
      interferon-gamma-induced protein-10 from cultured human fetal astrocytes.
AB  - Thrombin is a multifunctional serine proteinase that induces a variety of
      responses from neural cells by cleavage of proteinase-activated receptors (PARs)
      including PAR1 and PAR4. Thrombin/PAR signaling has been implicated in the
      neuroinflammatory response that occurs in the brain following stroke and other
      central nervous system pathologies. The neuroinflammatory response involves
      astrocytes and results in induction of proinflammatory chemokines including
      interleukin-8 (IL-8 or CXCL8) and interferon-gamma-induced protein-10 (IP-10 or
      CXCL10) in these cells. Astroctyes are known to express PARs, however the effect
      of thrombin on astrocytic chemokine secretion is unknown. Here we characterize
      the ability of thrombin to induce proliferation/metabolic activity and chemokine
      secretion in primary human fetal astrocytes. Thrombin induces dose-dependent
      astrocyte proliferation as well as release of both IL-8 and IP-10, but not IL-6
      or the chemokine regulated and normal T cell expressed and secreted (RANTES). The
      chemokine responses were mimicked by PAR1, but not PAR4, activating peptides. Our
      data indicate that astrocytic chemokine release is part of the neuroinflammatory
      response triggered by the exposure of the central nervous system to thrombin.

PMID- 23168566
TI  - Estimation of genetic effects on BMI during adolescence in an ethnically diverse
      cohort: The National Longitudinal Study of Adolescent Health.
AB  - OBJECTIVE: The contribution of genetic variants to body mass index (BMI) during
      adolescence across multiethnic samples is largely unknown. We selected genetic
      loci associated with BMI or obesity in European-descent samples and examined them
      in a multiethnic adolescent sample. DESIGN AND SAMPLE: In 5103 European American
      (EA), 1748 African American (AfA), 1304 Hispanic American (HA) and 439 Asian
      American (AsA) participants of the National Longitudinal Study of Adolescent
      Health (Add Health; ages 12-21 years, 47.5% male), we assessed the association
      between 41 established obesity-related single-nucleotide polymorphisms (SNPs)
      with BMI using additive genetic models, stratified by race/ethnicity, and in a
      pooled meta-analysis sample. We also compared the magnitude of effect for BMI-SNP
      associations in EA and AfA adolescents to comparable effect estimates from 11 861
      EA and AfA adults in the Atherosclerosis Risk in Communities study (ages 45-64
      years, 43.2% male). RESULTS: Thirty-five of 41 BMI-SNP associations were
      directionally consistent with published studies in European populations, 18
      achieved nominal significance (P<0.05; effect sizes from 0.19 to 0.71 kg m(-2)
      increase in BMI per effect allele), while 4 (FTO, TMEM18, TFAP2B, MC4R) remained
      significant after Bonferroni correction (P<0.0015). Of 41 BMI-SNP associations in
      AfA, HA and AsA adolescents, nine, three and five, respectively, were
      directionally consistent and nominally significant. In the pooled meta-analysis,
      36 of 41 effect estimates were directionally consistent and 21 of 36 were
      nominally significant. In EA adolescents, BMI effect estimates were larger
      (P<0.05) for variants near TMEM18, PTER and MC4R and smaller for variants near
      MTIF3 and NRXN3 compared with EA adults. CONCLUSION: Our findings suggest that
      obesity susceptibility loci may have a comparatively stronger role during
      adolescence than during adulthood, with variation across race/ethnic
      subpopulation.

PMID- 23168568
TI  - A thiazolothiazole based Cu2+ selective colorimetric and fluorescent sensor via
      unique radical formation.
AB  - A novel thiazolothiazole-based Cu(2+) colorimetric and fluorescent sensor is
      reported. A highly selective colorimetric change from yellow to dark green was
      observed among various metal ions after adding Cu(2+). Unique radical formation
      can engender these highly selective colorimetric and fluorescent changes.

PMID- 23168567
TI  - Women's exposure to phthalates in relation to use of personal care products.
AB  - Several phthalates, particularly diethyl phthalate (DEP) and di-n-butyl
      phthalate, can be used in personal care products (PCPs) to fix fragrance and hold
      color. We investigated associations between women's reported use of PCPs within
      the 24 h before urine collection and concentrations of several urinary phthalate
      metabolites. Between 2002 and 2005, 337 women provided spot urine samples and
      answered questions regarding their use of 13 PCPs at a follow-up visit 3-36
      months after pregnancy. We examined associations between urinary concentrations
      of several phthalate metabolites and use of PCPs using linear regression. Use of
      individual PCPs ranged from 7% (nail polish) to 91% (deodorant). After adjusting
      for age, education, and urinary creatinine, women reporting use of perfume had
      2.92 times higher (95% CI: 2.20-3.89) concentration of monoethyl phthalate (MEP;
      the primary metabolite of DEP) than other women. Other PCPs that were
      significantly associated with MEP concentrations included: hair spray, nail
      polish, and deodorant. MEP concentrations increased with the number of PCPs used.
      PCP use was widespread in this group of recently pregnant women. Women's use of
      PCPs, particularly of perfumes and fragranced products, was positively associated
      with urinary concentration of multiple phthalate metabolites.

PMID- 23168569
TI  - Hemoglobin A1c and short-term outcomes in patients with acute myocardial
      infarction undergoing primary angioplasty:  an observational multicenter study.
AB  - OBJECTIVE: Several studies to date have examined whether admission levels of
      hemoglobin A1c (HbA1c) correlate with short-term and long-term outcomes in
      patients with acute myocardial infarction treated with primary percutaneous
      coronary intervention (PCI). However, the results have been ambiguous. We
      speculated that admission levels of HbA1c correlate with short-term outcomes of
      patients with ST-elevation myocardial infarction (STEMI) undergoing primary PCI.
      METHODS: In this observational multicenter study, 608 patients with STEMI who
      underwent primary PCI between June 2001 and July 2004 were enrolled. Blood
      samples were collected upon admission to hospital for HbA1c measurement. Follow
      up was carried out at 7 and 30 days after hospital admission. According to the
      new American Diabetes Association criteria, patients were stratified into three
      groups: I, HbA1c 5.6% or less (n=262); II, HbA1c 5.7-6.4% (n=182); and III, HbA1c
      at least 6.5% (n=164). The primary outcomes were all-cause mortality and major
      adverse cardiac events at follow-up. RESULTS: The 7-day mortality was similar
      (P=0.179) between groups I (1.9%), II (2.2%), and III (0.0%); the 30-day
      mortality was also similar (P=0.241) between groups I (3.8%), II (2.2%), and III
      (1.2%). MACE at the 7- day and 30-day follow-up were not significantly different
      between the three groups either (P>0.05). Rates of target vessel
      revascularization and rehospitalization, and MACE-free survival curves, at the 30
      day follow-up were also similar among the three groups. After adjusting the
      baseline characteristics, HbA1c was not an independent predictor of short-term
      outcomes (hazards ratio: 0.431; 95% confidence interval: 0.175-1.061, P=0.067).
      CONCLUSION: Admission levels of HbA1c are not an independent prognostic marker
      for short-term outcomes in STEMI patients treated with primary PCI.

PMID- 23168570
TI  - A branched electrode based electrochemical platform: towards new label-free and
      reagentless simultaneous detection of two biomarkers.
AB  - A branched electrode platform was proposed for label-free and reagentless
      simultaneous tumor markers detection based on different redox substrates.

PMID- 23168572
TI  - Self-assembly of a tetrahedral 58-nuclear barium vanadium oxide cluster.
AB  - We report the synthesis and characterization of a molecular barium vanadium oxide
      cluster featuring high nuclearity and high symmetry. The tetrameric, 2.3 nm
      cluster H(5)[Ba(10)(NMP)(14)(H(2)O)(8)[V(12)O(33)](4)Br] is based on a bromide
      centred, octahedral barium scaffold which is capped by four previously unknown
      [V(12)O(33)](6-) clusters in a tetrahedral fashion. The compound represents the
      largest polyoxovanadate-based heterometallic cluster known to date. The cluster
      is formed in organic solution and it is suggested that the bulky N-methyl-2
      pyrrolidone (NMP) solvent ligands allow the isolation of this giant molecule and
      prevent further condensation to a solid-state metal oxide. The cluster is fully
      characterized using single-crystal XRD, elemental analysis, ESI mass spectrometry
      and other spectroscopic techniques.

PMID- 23168573
TI  - Glomerular expression of fractalkine is induced by polyinosinic-polycytidylic
      acid in human mesangial cells: possible involvement of fractalkine after viral
      infection.
AB  - BACKGROUND: Viral infections often trigger the onset or worsening of glomerular
      diseases, but the details of this mechanism are unclear. Fractalkine/CX3CL1 (Fkn)
      is a chemokine that induces the chemotaxis and activation of cells expressing its
      receptor, CX3CR1. To examine the involvement of glomerular Fkn expression in the
      development of glomerulonephritis after viral infection, we conducted
      experimental studies using human mesangial cells (MCs) in culture. METHODS: We
      examined the effect of polyinosinic-polycytidylic acid (poly IC), an authentic
      viral double-stranded RNA, on Fkn expression in MCs to investigate the
      involvement of Fkn in the antiviral reaction of MCs. Fkn mRNA and protein were
      analyzed using real-time PCR and enzyme-linked immunosorbent assay. Also, an
      immunofluorescent study to examine mesangial Fkn expression in biopsy specimens
      obtained from patients with glomerulonephritis was conducted. RESULTS: Poly IC
      induced Fkn expression in MCs in both a time- and dose-dependent manner, and RNA
      interference (RNAi) against Toll-like receptor 3 (TLR3) or interferon regulatory
      factor 3 (IRF3) inhibited poly IC-induced Fkn expression. Significant glomerular
      Fkn expression was observed in biopsy specimens from patients with immunoglobulin
      A nephropathy and purpura nephritis, with increasing severity of glomerular
      inflammation. CONCLUSION: The TLR3/IRF3/Fkn signaling pathway may, at least in
      part, mediate immune and inflammatory responses against viral infection in MCs.

PMID- 23168574
TI  - Head-to-head comparison of single-breath and tidal-breath exhaled nitric oxide
      measurements.
AB  - BACKGROUND: Exhaled nitric oxide (eNO) is an endogenous gas involved in airway
      pathophysiology and is determined in orally exhaled air by various techniques.
      However, traditional single-breath technique (eNO(SB)) requires active
      cooperation and is not always easily practicable (especially in young children);
      simpler techniques including tidal breathing measurements (eNO(TB)) are not
      standardized. The aim of this study was to evaluate the possible correlation and
      correspondence between eNO(SB) and eNO(TB) and the impact of potential
      confounders in children with chronic adenotonsillar disease. METHODS: Eighty-six
      children (mean age 8.7 +/- 3.2 y) underwent eNO assessment by means of eNO(SB)
      and eNO(TB). The correlation among eNO(TB), eNO(SB), and other potential
      confounders (i.e., gender, age, weight, height, BMI, and passive smoking
      exposure) were studied. RESULTS: The analyses showed a poor correspondence
      between eNO(SB) and eNO(TB), with the latter underestimating (P < 0.001) mean eNO
      values: 6.4 parts per billion (ppb) (95% confidence interval (CI): 8.4-11.4 ppb)
      vs. 9.8 ppb (95% CI: 5.6-7.3 ppb). A greater correlation was found between
      eNO(SB) and eNO(TB) in children younger than 6 y. Only eNO(SB) and age predicted
      eNO(TB) (R2 = 43.6%). CONCLUSION: eNO(TB) is not a good predictor of eNO(SB) in
      children. Constant-flow eNO(SB) is the technique of choice for eNO assessment in
      young children.

PMID- 23168576
TI  - Kawasaki disease and soy: potential role for isoflavone interaction with Fcgamma
      receptors.
AB  - Kawasaki disease (KD) is a diffuse vasculitis occurring in children and showing
      predilection for the coronary arteries. The etiology remains unknown, although
      some risk factors for susceptibility have been defined. Asian ethnicity is a
      primary risk factor. Several theories have circulated regarding the differences
      in KD ethnic incidence. Those theories implicating genetic differences among
      populations as the cause for this discrepancy have dominated and are areas of
      active investigation by multiple research groups. Differences in diet between
      Asians and Westerners are touted as reasons for certain ethnic-related
      discrepancies in susceptibility to cardiovascular disease and cancer in adults.
      Surprisingly, these cultural dietary differences have not been previously
      considered as the source of the discrepancy in KD incidence among these ethnic
      populations. Recent data from genetic studies have highlighted the role of
      specific immune receptors in the pathogenesis of KD. Functions of the Fcgamma
      receptors (FcGRs) are modulated by isoflavones in soy, in particular, genistein.
      Epidemiological data from Hawaiian populations support an association between soy
      consumption and KD. These observations form the basis of a hypothesis:
      isoflavones participate in KD pathogenesis by modulating function of the FcGRs
      and by disrupting the balance between activation and inhibition of the
      inflammatory response.

PMID- 23168575
TI  - Candidate gene linkage approach to identify DNA variants that predispose to
      preterm birth.
AB  - BACKGROUND: The aim of this study was to identify genetic variants contributing
      to preterm birth (PTB) using a linkage candidate gene approach. METHODS: We
      studied 99 single-nucleotide polymorphisms (SNPs) for 33 genes in 257 families
      with PTBs segregating. Nonparametric and parametric analyses were used. Premature
      infants and mothers of premature infants were defined as affected cases in
      independent analyses. RESULTS: Analyses with the infant as the case identified
      two genes with evidence of linkage: CRHR1 (P = 0.0012) and CYP2E1 (P = 0.0011).
      Analyses with the mother as the case identified four genes with evidence of
      linkage: ENPP1 (P = 0.003), IGFBP3 (P = 0.006), DHCR7 (P = 0.009), and TRAF2 (P =
      0.01). DNA sequence analysis of the coding exons and splice sites for CRHR1 and
      TRAF2 identified no new likely etiologic variants. CONCLUSION: These findings
      suggest the involvement of six genes acting through the infant and/or the mother
      in the etiology of PTB.

PMID- 23168577
TI  - Brain inflammation induced by severe asphyxia in newborn pigs and the impact of
      alternative resuscitation strategies on the newborn central nervous system.
AB  - BACKGROUND: We compared the current guidelines for neonatal resuscitation with
      alternative measures and aimed to find out whether this modulated brain
      inflammation. METHODS: Progressive asphyxia was induced in 94 newborn pigs until
      asystole. With the reference being resuscitation guidelines, 30 s of initial
      positive-pressure ventilation before compression (C) and ventilation (V) (C:V;
      3:1) in 21% oxygen, pigs were randomized to (i) ventilation for 30, 60, or 90 s
      before chest compressions; (ii) C:V ratios of 3:1, 9:3, or 15:2; or (iii) 21% or
      100% oxygen. Concentrations of inflammatory markers in the cerebrospinal fluid
      (CSF) and gene expression in the hippocampus and frontal cortex were measured for
      different interventions. RESULTS: In CSF, S100 was higher with 90 s than with 30
      or 60 s of initial positive-pressure ventilation, whereas concentrations of
      interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) were higher with
      30 than with 60 s. Matrix metalloproteinase-2 (MMP-2) and intracellular adhesion
      molecule 1 (ICAM-1) were higher with 30 than with 60 s. No other comparison
      between ratios and oxygen concentrations used yielded significant results.
      CONCLUSION: With respect to signs of brain inflammation, newly born pigs at
      asystole should be ventilated for longer than 30 s before chest compressions
      start. C:V ratios of 9:3 and 15:2 as compared with 3:1, or air instead of pure
      oxygen, did not modulate inflammatory markers.

PMID- 23168578
TI  - Evaluating iron status and the risk of anemia in young infants using erythrocyte
      parameters.
AB  - BACKGROUND: Correct evaluation of iron status is important in young infants
      because both iron deficiency and excess may have negative effects on development,
      growth, and morbidity. METHODS: We evaluated iron status using erythrocyte
      parameters, including reticulocyte hemoglobin content (CHr) in infants with birth
      weight <3,000 g (n = 80). Blood samples and infant characteristics were recorded
      at 6 wk and at 4 and 6 months. Infants with a birth weight <=2,500 g (n = 36)
      were recommended for iron supplementation. RESULTS: Despite a significantly
      poorer status at 6 wk, iron-supplemented infants had significantly higher
      hemoglobin level (Hb): 12.2 (SD = 0.8) g/dl and CHr: 28.3 (SD = 1.4) pg at 6 mo,
      as compared with nonsupplemented infants, Hb: 11.7 (SD = 1.0) g/dl, P = 0.02 and
      CHr: 26.5 (SD = 2.5) pg, P < 0.001. Prolonged exclusive breastfeeding, high
      weight gain, and male gender were the predisposing factors for a low iron status
      at 6 mo. A CHr cutoff level of 26.9 pg at 4 mo proved to be a sensitive predictor
      for anemia at 6 mo. CONCLUSION: Signs of an iron-restricted erythropoiesis were
      observed in nonsupplemented infants (birth weight 2,501-3,000 g), and CHr was a
      useful tool for evaluating iron status. The need for iron supplementation in
      certain infant risk populations should be further evaluated.

PMID- 23168579
TI  - Unusual regenerable porous metal-organic framework based on a new triple helical
      molecular necklace for separating organosulfur compounds.
AB  - Desulfurization of fuels is receiving more and more attention all over the world
      due to the increase of stringent environmental regulations and fuel
      specifications. The metal-organic framework (MOF) is a new class of crystalline
      materials, and high porosity, one of the most important properties of MOFs, plays
      a central role in the functional properties. However, the investigation of MOFs,
      being employed as sorbents for adsorptive desulfurization, is still scarce. In
      this regard, we have constructed a new 3D porous compound 1 by using rigidly
      designed carboxylate ligands, which, for the first time, exhibit an unusual
      triple molecular necklace-like helix. The N(2)  sorption isotherms of 1 show that
      it has a large Brunauer-Emmett-Teller (BET) surface area and pore volume. With
      the stable pore structure and appropriate pore sizes, compound 1 has been used as
      a sorbent for adsorptive desulfurization. The results indicate that compound 1
      shows an excellent adsorption property and, more importantly, displays excellent
      stability, repeatability, and regenerability. Thus, the design and synthesis of
      targeted MOFs with appropriate pore size and increased interactions between
      organosulfur compounds and ligands/metals from MOFs is crucial for adsorptive
      desulfurization, which might be an effective guide to find an efficient and green
      adsorbent for desulfurization.

PMID- 23168582
TI  - President's Reflections.

PMID- 23168580
TI  - Chlorogenic acid attenuates high mobility group box 1 (HMGB1) and enhances host
      defense mechanisms in murine sepsis.
AB  - Sepsis is a complex, multifactorial, rapidly progressive disease characterized by
      an overwhelming activation of the immune system and the countervailing
      antiinflammatory response. In the current study in murine peritoneal macrophages,
      chlorogenic acid suppressed endotoxin-induced high mobility group box 1 (HMGB1)
      release in a concentration-dependent manner. Administration of chlorogenic acid
      also attenuated systemic HMGB1 accumulation in vivo and prevented mortality
      induced by endotoxemia and polymicrobial sepsis. The mechanisms of action of
      chlorogenic acid included attenuation of the increase in toll-like receptor (TLR)
      4 expression and suppression of sepsis-induced signaling pathways, such as c-Jun
      NH2-terminal kinase (JNK), p38 mitogen-activated protein kinase (MAPK) and
      nuclear factor (NF)-kappaB, which are critical for cytokine release. The
      protection conferred by chlorogenic acid was achieved through modulation of
      cytokine and chemokine release, suppression of immune cell apoptosis and
      augmentation of bacterial elimination. Chlorogenic acid warrants further
      evaluation as a potential therapeutic agent for the treatment of sepsis and other
      potentially fatal systemic inflammatory disorders.

PMID- 23168583
TI  - Surgical biopsy for diffuse parenchymal lung diseases: are we causing more harm
      than good?

PMID- 23168581
TI  - Safety and efficacy of ARA 290 in sarcoidosis patients with symptoms of small
      fiber neuropathy: a randomized, double-blind pilot study.
AB  - ARA 290 (a peptide designed to activate the innate repair receptor that arrests
      injury and initiates cytoprotection, antiinflammation and healing) reduces
      allodynia in preclinical neuropathy models. We studied the safety and efficacy of
      ARA 290 to reduce symptoms of small fiber neuropathy (SFN) in patients with
      sarcoidosis. A total of 22 patients diagnosed with sarcoidosis and symptoms of
      SFN were enrolled in a double-blind, placebo-controlled exploratory trial
      consisting of three times weekly intravenous dosing of ARA 290 (2 mg; n = 12) or
      placebo (n = 10) for 4 wks. Inclusion criteria were a diagnosis of neuropathy and
      a spontaneous pain score of >=5 (Brief Pain Inventory [BPI]). Endpoints assessed
      were changes in pain intensity and the small fiber neuropathy screening list
      (SFNSL) score, quality of life (SF-36), depressive symptoms (Inventory of
      Depressive Symptomatology [IDS]) and fatigue (Fatigue Assessment Scale [FAS]). No
      safety concerns were raised by clinical or laboratory assessments. The ARA 290
      group showed significant (p < 0.05) improvement at wk 4 in SFNSL score compared
      with placebo (Delta -11.5 +/- 3.04 versus Delta -2.9 +/- 3.34 [standard error of
      the mean]). Additionally, the ARA 290 group showed a significant change from
      baseline in the pain and physical functioning dimensions of the SF-36 (Delta 
      23.4 +/- 5.5 and Delta -14.6 +/- 3.9, respectively). The mean BPI and FAS scores
      improved significantly but equivalently in both patient groups. No change was
      observed in the IDS. ARA 290 appears to be safe in patients with sarcoidosis and
      can reduce neuropathic symptoms.

PMID- 23168584
TI  - Risk of Acute Exacerbation After Video-assisted Thoracoscopic Lung Biopsy for
      Interstitial Lung Disease.
AB  - Biopsy by video-assisted thoracoscopic surgery (VATS) for interstitial pneumonia
      allows collection of samples sufficient for accurate histologic diagnosis.
      Although VATS is relatively safe, several reports have suggested that surgical
      lung biopsy may be a risk factor for acute exacerbation of idiopathic pulmonary
      fibrosis (IPF). We retrospectively reviewed data on the 113 cases that underwent
      biopsy by VATS to diagnose diffuse parenchymal lung disease in our department
      between 1994 and 2006, and analyzed its complications, in particular, risk of
      acute exacerbation of IPF. As the final diagnosis, idiopathic interstitial
      pneumonia was most frequent, involving 52 cases, of which IPF was most frequently
      found followed by nonspecific interstitial pneumonia and cryptogenic organizing
      pneumonia, in that order. Among our cases, there were 2 deaths after VATS
      (mortality rate, 1.8%), and both were IPF cases with acute exacerbation. When
      examining clinical markers in the 2 fatal IPF cases with acute exacerbation, we
      found that the percentage of predicted forced vital capacity was 55 or lower,
      percentage of predicted carbon monoxide diffusing capacity was 40 or lower, serum
      interstitial pneumonia markers KL-6 and SP-D were elevated, intraoperative
      inhalation of 100% O2 was 80 minutes or longer, and postoperative thoracic
      drainage was required for 10 days or longer. Although acute exacerbations of IPF
      seem to occur at any time during the course of disease, it is important to be
      aware of the possibility of acute exacerbation of IPF after VATS.

PMID- 23168585
TI  - Autoaspiration versus manual aspiration in transbronchial needle aspiration in
      diagnosis of intrathoracic lymphadenopathy.
AB  - BACKGROUND: Traditionally, aspiration with high negative pressure is recommended
      to obtain a specimen in transbronchial needle aspiration (TBNA). Undeniably,
      however, the assistant experiences difficulty in the generation of the negative
      pressure and precise control of the syringe while performing the procedure.
      OBJECTIVE: To evaluate the effectiveness of the autoaspiration method created by
      our plunger lock in comparison with the conventional manual aspiration in the
      diagnosis of intrathoracic lymphadenopathy by TBNA. METHODS: A prospective study
      was conducted on all patients referred for diagnostic TBNA of enlarged
      intrathoracic lymph nodes. Both automatic and manual aspiration techniques were
      performed after the needle had been completely inserted into the nodes. The
      diagnostic yield and the numbers of diagnostic cells or benign lymphoid cells
      obtained by each technique were compared in the same node. RESULTS: A total of 31
      intrathoracic lymph nodes in 24 patients were prospectively studied. Twenty-four
      nodes (77.4%) were malignancies whereas 7 nodes (22.6%) were benign disease.
      Adequate lymph node samples were obtained in 30 targets (96.8%), and TBNA
      revealed definite diagnosis for 25 nodes (80.6%). Both aspiration techniques
      showed exactly the same diagnostic yield. However, the autoaspiration technique
      provided significantly more adequate samples than manual aspiration techniques
      did (P=0.003). CONCLUSION: The autoaspiration method using our plunger lock was
      superior to the manual method in obtaining the numbers of adequate samples in
      TBNA procedures.

PMID- 23168586
TI  - Bispectral index monitoring of midazolam sedation during flexible bronchoscopy.
AB  - BACKGROUND: Flexible bronchoscopy could be an uncomfortable examination for some
      patients. The purpose of this study was to examine the patient characteristics
      associated with "patient satisfaction" with sedation during flexible
      bronchoscopy. METHOD: Fifty-two patients undergoing diagnostic flexible
      bronchoscopy were divided into 2 groups. Group A (n=44) comprised patients who
      felt that the sedation was satisfactory, and group B (n=8) comprised patients who
      felt otherwise. All patients were given midazolam to maintain Ramsay sedation
      scores of 2 to 3. We measured blood pressure, heart rate, respiratory rate,
      oxygen saturation, and bispectral index scores (BIS) every 5 minutes during
      bronchoscopy. Adverse events were also recorded. RESULTS: There were no
      significant differences between the 2 groups in terms of age, height, weight,
      blood pressure, heart rate, respiratory rate, oxygen saturation, duration of
      flexible bronchoscopy, or doses of lidocaine and midazolam. The BIS was
      significantly lower for group A than for group B. Adverse events that would lead
      to aborting the procedure were not encountered. CONCLUSIONS: We suggest that the
      BIS value during flexible bronchoscopy is associated with the satisfaction of
      patients and they may be able to predict patients' satisfaction.

PMID- 23168587
TI  - Photodynamic therapy in the management of endobronchial metastatic lesions from
      renal cell carcinoma.
AB  - STUDY OBJECTIVES: Bronchoscopic procedures to ablate endobronchial lesions (EBL)
      from renal cell carcinoma (RCC) are frequently complicated by hemorrhage because
      of the vascular nature of the metastases. After ablation, recurrence of symptoms
      from the EBLs is common. Photodynamic therapy (PDT), because of its mode of
      action, may be a safer and a more effective alternative in the nonemergent
      management of EBL from RCC. METHODS: Medical records of patients undergoing PDT
      at the authors' institutions between December 2005 and December 2008 were
      reviewed and patients undergoing treatment for EBLs from RCC were identified.
      Procedure-related complications, 30-day mortality, and efficacy of PDT measured
      by recurrence in symptoms and the need for additional interventions on the
      treated EBLs were reviewed. RESULTS: Eleven patients underwent a total of 13
      treatments with PDT. Hemoptysis, with or without symptomatic airway obstruction,
      was the most common presenting symptom. The most common location for the EBLs was
      the lobar or segmental bronchi. Six patients had undergone other interventions
      (rigid bronchoscopy, mechanical debridement, or argon plasma coagulation) before
      treatment with PDT, with recurrence in symptoms. No immediate complications were
      seen with PDT and none of the patients had recurrence of symptoms or required
      airway interventions during the 30-day follow-up. Four patients died at a median
      of 4 months (range: 3 to 6 mo) after PDT and all deaths were due to progression
      of cancer and none of the deaths were due to airway complications. CONCLUSIONS:
      PDT is a safe and effective option for the management of hemoptysis or airway
      obstruction caused by EBLs from RCC.

PMID- 23168588
TI  - Pleuroscopy: early experience in an East malaysian state with high tuberculosis
      prevalence.
AB  - INTRODUCTION: Pleuroscopy using a flexi-rigid tube was introduced in Malaysia in
      late 2004 as part of the investigation for unexplained pleural effusion. Sabah,
      an East Malaysian state situated in Borneo, has the highest prevalence of
      tuberculosis (TB) in Malaysia. Therefore, exudative pleural effusion in Sabah was
      presumed to be predominantly because of TB. OBJECTIVE: To look at the diagnostic
      yield and safety of pleuroscopy in a TB endemic state in Malaysia. METHODS: A
      prospective study was conducted covering the period from September 2006 to May
      2007. Consecutive patients with unexplained pleural effusion underwent
      pleuroscopy. Biopsy was performed if nodules, nodules with adhesions, or
      adhesions were visualized in the pleural space. Data were analyzed using the chi
      test and multivariate analysis. A P value of less than 0.05 was taken as
      statistically significant. RESULTS: Sixty-two patients underwent pleuroscopy.
      Biopsy specimens were obtained in 55 of 57 patients (96.4%). The diagnostic yield
      of nodules, nodules with adhesions, and adhesions was 92.0%, 66.7%, and 60.0%,
      respectively. TB and neoplasm were diagnosed in 22 (52.4%) and 20 (47.6%)
      patients, respectively. Neoplasm was more common in female patients and TB was
      more common in male patients (P=0.048). Neither neoplasm nor TB was significantly
      associated with ethnic groups (P=0.156). Sensitivity of the initial impression
      for TB and neoplasm was 59.1% and 90.0%, respectively. One patient experienced
      desaturation during pleuroscopy. CONCLUSIONS: Pleuroscopy is a safe diagnostic
      procedure and especially useful in sampling nodules indicating that the sample
      size obtained during pleuroscopy is satisfactory. Empirical TB treatment should
      be discouraged even in a state with high TB prevalence as certain neoplasms can
      present as pleural effusion. Pleuroscopy should be performed early in unexplained
      pleural effusion.

PMID- 23168589
TI  - Benign tracheal stenosis: a case series analysis.
AB  - Tracheal stenosis (TS) requires a precise diagnosis and an experienced operator
      in both endoscopic and surgical treatment. We describe a case series at a
      tertiary care teaching hospital. Twenty patients with TS and/or subglottic
      stenosis were included. All underwent flexible bronchoscopy (FB). Spirometry (SP)
      was obtained in 8 patients, and helical computed tomography with three
      dimensional reconstruction (HCT3D) was obtained in 11 patients. All cases were
      graded by each modality on a scale of 1 to 3, and the findings were correlated
      among modalities. Mean follow-up was 11.1 months (range: 3 to 47 mo).
      Postintubation injury was the most frequent cause of stenosis in 16 patients
      (80%). Mean stenosis grade+/-SD was 2.0+/-0.92 for SP, 2.3+/-0.86 for FB, and
      2.54+/-0.68 for HCT3D. A significant correlation was found between HCT3D and FB
      (r=0.76, P<0.01). There was no correlation between SP and FB (r=0.46, P=0.2) or
      between SP and HCT3D (r=0.68, P=0.13). Treatment was conservative in 8 patients.
      Eighteen tracheal dilatation procedures were performed in 7 patients (mean: 2.5
      dilatations/patient, range: 1 to 6; mean free time between dilatations 109.7+/-81
      d, range: 6 to 210 d). Tracheoplasty was carried out in 7 patients, with tracheal
      anastomosis in 4 patients and thyroid-tracheal anastomosis in 3 patients.
      Tracheostomy was required in 1 patient with scleroma. Neither complications nor
      mortality related to FB was reported. HCT3D has a good correlation with FB.
      Tracheal dilatation is a viable option for patients who are not surgical
      candidates and for those with restenosis of tracheal anastomosis.

PMID- 23168590
TI  - Transbronchial Biopsy for Peripheral Pulmonary Lesions Under Real-time
      Endobronchial Ultrasonographic Guidance.
AB  - BACKGROUND AND OBJECTIVES: Transbronchial biopsy (TBB) using endobronchial
      ultrasonography with a guide sheath (EBUS-GS) is a promising technique for small
      peripheral pulmonary lesions (PPLs), but is not a real-time procedure. We
      attempted to examine the practicality of TBB under real-time EBUS guidance for
      PPLs. METHODS: We performed TBB under real-time EBUS and x-ray fluoroscopic
      guidance using flexible bronchoscopy with 2 working channels for PPLs (mean
      diameter,>30 mm). RESULTS: Between January 2007 and May 2007, we recruited 6
      patients for this trial. On computed tomography images, the mean+/-SD diameter of
      the lesions was 37.4+/-4.5 mm (range: 32.0 to 45.0 mm). All lesions were detected
      by EBUS and could eventually be diagnosed. However, an image of the biopsy
      forceps or brush was obtained on real-time EBUS in only 4 cases. The other 2
      cases involved technical limitations in inserting both the EBUS probe and biopsy
      forceps simultaneously into the lesion. Unfortunately, even in the 4 cases in
      which biopsy forceps images could be obtained on real-time EBUS, we could not
      recognize the position of the tip of the forceps on EBUS images, because the EBUS
      images of the tip of the forceps and the body of forceps were very similar.
      CONCLUSIONS: Our attempt to perform TBB under real-time EBUS guidance for PPLs
      was successful in 4 of 6 patients. There were some technical limitations using
      flexible bronchoscopy with 2 working channels. Improvement of instruments will be
      necessary for future trials of TBB under real-time EBUS guidance.

PMID- 23168591
TI  - Bronchoscopic view of pulmonary blastomycosis.
AB  - Blastomycosis is a chronic fungal infection often diagnosed in the south-central
      and midwestern United States. Lungs are primarily involved, with lymphatic or
      hematogenous spread to other organs. Bronchoscopy is considered when the
      noninvasive tests fail to establish the diagnosis. We describe bronchoscopic
      finding of blastomycosis involving the upper and lower respiratory tract. Inhaled
      steroids may have suppressed cellular immunity, allowing fungus to grow in the
      submucosa with histology significant for extensive eosinophilic infiltration. To
      our knowledge, such a detailed pictorial description of pulmonary blastomycosis
      with a cobblestone appearance of the tracheobronchial mucosa has not been
      reported in the past.

PMID- 23168592
TI  - Chondroma: an uncommon case of bronchial tumor.
AB  - We report the case of a patient with an endobronchial chondroma, a rare benign
      endobronchial tumor. A 37-year-old woman was evaluated for suspicion of asthma.
      Computed tomography of the chest and flexible bronchoscopy showed an endoluminal
      tumor occluding the culmen (B3 left). The tumor was extirpated almost completely
      by bronchoscopy. Histologically, the biopsy specimens were composed of
      chondromatous tissue located under the normal bronchial mucosa, according to the
      diagnosis of chondroma. The symptoms disappeared immediately after the procedure
      and did not reappear after 1 year. Chondromas are usually located on the
      skeleton. Endobronchial presentation is rare. We know of only 41 cases reported
      in the literature. Hamartoma or chondrosarcoma constitutes the main histologic
      differential diagnosis. The treatment consists of complete resection to avoid any
      risk of recurrence or sarcomatous transformation. There is no consensus regarding
      the method of treatment, but endoscopic resection seems to be the first choice.

PMID- 23168593
TI  - Pulmonary artery pseudoaneurysm arising from a lung tumor.
AB  - A 48-year-old smoker and alcoholic patient was admitted for life-threatening
      hemoptysis. The admission bronchoscopy showed a tumoral mass almost occluding the
      right bronchus intermedious. During the procedure the patient developed massive
      bleeding and underwent selective aortic angiogram and coiling of 2 bronchial
      arteries. After the patient stabilized, a contrast thoracic computed tomography
      was performed, revealing a right pulmonary artery pseudoaneurysm. On the basis of
      that finding, a selective right pulmonary artery angiogram was performed, showing
      a 3.4-cm-diameter pseudoaneurysm that was embolized. Hemoptysis resolved after
      the procedure, but the patient developed parenchymal ischemia-infarct on the
      treated area (right lower lobe). A pulmonary artery pseudoaneurysm can arise from
      a lung tumor and cause massive hemoptysis. Although unusual, ischemia and infarct
      can occur after embolotherapy.

PMID- 23168594
TI  - Adult-onset Still's Disease With Pulmonary Involvement.
AB  - BACKGROUND: Only a few earlier pathologic reports exist describing adult-onset
      Still's disease (AOSD) with pulmonary involvement. We report a case of AOSD with
      pulmonary involvement producing an organizing pneumonia pattern as seen on
      transbronchial lung biopsy (TBLB). CASE: A 67-year-old man was referred with
      fever, cough, and multiple joint pains. Chest x-ray revealed an infiltration in
      the right upper lung field, and chest high-resolution computed tomography showed
      a consolidation in the right upper lobe segment. The patient did not respond to
      multiple antibiotics, and remittent fever over 38 degrees C persisted. The
      patient also developed a salmon-pink rash. AOSD was diagnosed according to
      specific diagnostic criteria. Organizing pneumonia was diagnosed by TBLB
      histology and radiologically, and the lesions were thought to be due to pulmonary
      involvement of AOSD. Treatment with prednisolone and a nonsteroidal anti
      inflammatory drug immediately improved the parenchymal lesions. CONCLUSIONS: AOSD
      can produce lung involvement. TBLB is useful in the diagnosis of pulmonary
      lesions.

PMID- 23168595
TI  - Tracheobronchial rhinoscleroma.
AB  - Rhinoscleroma is a chronic infectious disease caused by Klebsiella
      rhinoscleromatis. It initially involves the nasal cavity and can occasionally
      extend to the rest of the upper respiratory tract. We report a case of
      rhinoscleroma involving both the larynx and the tracheobronchial tree, presenting
      with recurrent respiratory infection.

PMID- 23168596
TI  - Inflammatory myofibroblastic tumor presenting as a large mass and a spontaneously
      resolving nodule in the lung.
AB  - A 21-year-old woman presented with nausea, vomiting, decrease in appetite, and
      weight loss of 6 months and right chest pain of 5 days' duration. Earlier
      diagnostic work-ups had been inconclusive, and she was referred for the
      evaluation of the bilateral lung lesions as seen on her chest x-ray. Thoracic
      computed tomography scan showed a 6-cm mass in the right lower lobe, a minimal
      right pleural effusion, and a peripheral 2-cm cavitary nodule in the inferior
      lingular segment. Ultrasonography-guided transthoracic cutting needle biopsy of
      the right-sided mass and following right lower lobectomy both yielded benign
      specimens pathologically assessed as "inflammatory myofibroblastic tumor." The
      chest x-ray and thoracic computed tomography scans obtained 1 month following the
      thoracotomy showed spontaneous and almost complete resolution of the left-sided
      nodule. In follow-up 1 year after the surgery, no clinical, laboratory, or
      radiologic recurrence was detected. She is being closely followed as an
      outpatient.

PMID- 23168597
TI  - Transanastomotic endobronchial migration of a pericardial flap.
AB  - A 36-year-old woman underwent left main bronchus sleeve resection for a typical
      carcinoid. The bronchial anastomosis was reinforced with a bovine pericardial
      flap fixed by fibrin glue. Six months after the surgery the patient presented
      with acute dyspnea. Flexible bronchoscopy disclosed an endoluminal migration of
      the pericardial flap through the anastomotic dehiscence and a cicatricial
      stenosis of the left upper bronchus. The migrated flap was successfully removed
      and the stenosis segment of the bronchus was dilated using a rigid bronchoscope.
      Two months after complete recovery from the bronchial dehiscence, the patient
      developed an anastomotic cicatricial stenosis, which was effectively treated by
      laser photoresection and mechanical dilatation. Eight months after the last
      procedure the patient remains symptom free.

PMID- 23168598
TI  - Idiopathic Progressive Tracheobronchial Stenosis of 20 Years' Duration: Response
      to Anti-inflammatory Treatment.
AB  - We report a unique case of progressive tracheobronchial stenosis in a 52-year-old
      woman who presented to us with stridor and dyspnea at rest. Her initial symptoms
      began 20 years earlier, at which time subglottic stenosis of ill-defined etiology
      necessitated tracheal resection with end-to-end anastomosis. Tracheal biopsy at
      the time revealed nonspecific inflammation without granulomas, vasculitis,
      infection, amyloidosis, or malignancy. Over subsequent years, she underwent
      multiple endobronchial laser resections of the trachea for recurrent disease. On
      presentation to us, flexible bronchoscopy showed inflammatory stenoses of the
      left mainstem bronchus and bronchus intermedius. Bronchial biopsy showed acute
      and chronic stromal inflammation with scattered plasma cells and myofibroblasts
      against a background of dense fibrosis. Review of the initial tracheal resection
      specimens and subsequent bronchial specimens revealed areas of high collagenous
      content with a relatively scant overall myofibroblastic cellular infiltrate;
      stains for S-100 and anaplastic lymphoma kinase were negative. A diagnosis of
      idiopathic tracheal stenosis was made with unusual accompanying bronchial
      involvement, that is, idiopathic tracheobronchial stenosis. Inflammatory airway
      bronchostenoses were stabilized by high-dose steroids followed by weekly
      methotrexate therapy, as evidenced by serial flexible bronchoscopies and
      sequential chest computed tomography with 3-dimensional reconstruction imaging.
      To our knowledge, this is the first reported case of combined idiopathic tracheal
      and bronchial stenosis stabilized with anti-inflammatory treatment.

PMID- 23168599
TI  - ECMO-assisted Rigid Bronchoscopy for Tracheal Obstruction.
AB  - Extracorporeal membrane oxygenation in adults is typically reserved for thoracic
      or cardiac procedures in which insult to the pulmonary circuit has occurred or is
      anticipated. In this brief report, I describe a case of tracheal obstruction
      resulting from a retained tracheal stent that was removed through rigid
      bronchoscopy with extracorporeal membrane oxygenation support.

PMID- 23168600
TI  - Endobronchial hamartoma causing massive hemoptysis.
AB  - Endobronchial hamartoma is an unusual clinical entity and infrequently causes
      hemoptysis. This brief report extends the sparse available experience with
      endobronchial hamartoma causing hemoptysis by presenting, to our knowledge, only
      the third such patient reported to have massive hemoptysis complicating an
      endobronchial hamartoma.

PMID- 23168601
TI  - Extensive cryptococcal tracheitis mimicking lymphoma in an AIDS patient.
AB  - We describe a case of a 35-year-old man with human immunodeficiency virus
      infection/acquired immune deficiency syndrome presenting from an outside hospital
      with a diagnosis of non-Hodgkin's B-cell lymphoma. Radiologic imaging showed an
      infiltrative process with significant tracheal involvement and increased uptake
      of 18-fluoro-2-deoxyglucose on positron emission tomography. These findings were
      suspicious for non-Hodgkin's B-cell lymphoma. Flexible bronchoscopy and tissue
      sampling revealed cryptococcal infection of the trachea. This case presentation
      is of extensive cryptococcal tracheitis, an extremely rare presentation of
      endobronchial cryptococcosis. It also emphasizes the difficult radiologic
      distinction between such unusual endobronchial infections and malignancy.

PMID- 23168602
TI  - Circumferential calcified tracheal stenosis.
AB  - There are multiple etiologies for tracheal stenosis, postintubation stenosis
      being the most common. In this study, we briefly report a unique form of tracheal
      stenosis with circumferential calcification at the site of the lesion. The
      patient underwent multiple therapeutic bronchoscopies for palliation without much
      relief.

PMID- 23168607
TI  - Differential response to LPS isotypes induced platelet activation mediated by
      Toll-like receptor (TLR)-4.

PMID- 23168606
TI  - What predicts and what mediates the response of urge urinary incontinence to
      biofeedback?
AB  - AIMS: To better target a behavioral approach for urge urinary incontinence (UUI)
      and enhance its efficacy by (1) identifying predictors of response to biofeedback
      assisted pelvic muscle training (BFB), and (2) determining factors that mediate
      response. METHODS: BFB (four biweekly visits) was administered to 183 women > 60
      years (mean = 73.6). Before and after intervention, all underwent comprehensive
      evaluation and videourodynamic testing. Postulated predictors and mediators from
      four urodynamic domains, specified a priori, were correlated with reduction in
      UUI frequency. RESULTS: Median UUI frequency decreased from 3.2/day to 1/day (P
      =0.0001). UUI improved by >=50% in 55% of subjects and by 100% in 13% of
      subjects. Frequent UUI predicted poor response (P < 0.01). Of the urodynamic
      parameters, only high amplitude and briskness of detrusor overactivity (DO)
      predicted decreased response (P < 0.05 and P < 0.01) and these could be measured
      only in the 43% of subjects with elicitable DO. Decreased DO elicitability was
      the only urodynamic variable that changed in concert with improvement and thus
      was a candidate mediator. Response was neither predicted nor mediated by
      proprioception/warning, cystometric capacity, detrusor contractility, sphincter
      strength, or baseline DO elicitability. CONCLUSIONS: Severe DO predicts poor
      response to BFB. Good response is mediated by reduction in DO elicitability.
      Other than baseline UUI frequency, there are no other clinically or
      urodynamically important predictors or mediators of BFB response in this
      population. BFB may be best for patients with less severe DO. Future research to
      enhance its efficacy might better focus on the brain than on the lower urinary
      tract.

PMID- 23168608
TI  - Increased nerve vascularization detected by color Doppler sonography in patients
      with ulnar neuropathy at the elbow indicates axonal damage.
AB  - INTRODUCTION: The aim of this study was to establish the prevalence of increased
      intraneural vascularization detected by ultrasonography (IVUS) in patients with
      ulnar neuropathy at the elbow (UNE) and to determine its relationship to
      clinical, ultrasonographic, and electrodiagnostic findings. METHODS: High
      resolution ultrasonography and color Doppler imaging were performed in 137
      patients with confirmed UNE, 24 patient controls, and 70 healthy controls (HCs).
      RESULTS: IVUS was found in 21 (15%) of 137 patients with UNE, in 1 (4%) of 24
      patient controls, and in 0 of 70 HCs (P = 0.001). Patients with IVUS were more
      likely to have severe weakness (P = 0.01), severe atrophy of ulnar-innervated
      muscles (P = 0.008), axonal damage (P = 0.001), and more pronounced nerve
      enlargement (P = 0.03) than those without IVUS. CONCLUSIONS: IVUS in the ulnar
      nerve can be detected in patients with UNE and is associated with nerve
      enlargement and clinical and electrodiagnostic severity. In addition, IVUS is
      associated with axonal damage.

PMID- 23168609
TI  - Effects of resocialization on post-weaning social isolation-induced abnormal
      aggression and social deficits in rats.
AB  - As previously shown, rats isolated from weaning develop abnormal social and
      aggressive behavior characterized by biting attacks targeting vulnerable body
      parts of opponents, reduced attack signaling, and increased defensive behavior
      despite increased attack counts. Here we studied whether this form of violent
      aggression could be reversed by resocialization in adulthood. During the first
      weak of resocialization, isolation-reared rats showed multiple social deficits
      including increased defensiveness and decreased huddling during sleep. Deficits
      were markedly attenuated in the second and third weeks. Despite improved social
      functioning in groups, isolated rats readily showed abnormal features of
      aggression in a resident-intruder test performed after the 3-week-long
      resocialization. Thus, post-weaning social isolation-induced deficits in
      prosocial behavior were eliminated by resocialization during adulthood, but
      abnormal aggression was resilient to this treatment. Findings are compared to
      those obtained in humans who suffered early social maltreatment, and who also
      show social deficits and dysfunctional aggression in adulthood.

PMID- 23168610
TI  - Intraoral removal of stones in the proximal submandibular duct: usefulness of a
      surgical landmark for the hilum.

PMID- 23168611
TI  - Femoral venous oxygen saturation is no surrogate for central venous oxygen
      saturation.
AB  - OBJECTIVE: The purpose of our study was to determine if central venous oxygen
      saturation and femoral venous oxygen saturation can be used interchangeably
      during surgery and in critically ill patients. DESIGN: Prospective observational
      controlled study. SETTING: Nonacademic university-affiliated teaching hospital in
      The Netherlands. PATIENTS: One hundred cardiac outpatients, 30 high-risk surgical
      patients, and 30 critically ill patients. INTERVENTIONS: None. METHODS AND MAIN
      RESULTS: We concurrently determined femoral venous oxygen saturation and central
      venous oxygen saturation in a group of 100 stable cardiac patients, which served
      as control group. Furthermore, we determined simultaneously femoral venous oxygen
      saturation and central venous oxygen saturation in 30 surgical patients and in 30
      critically ill patients and evaluated changes over time. Correlation and
      agreement of femoral venous oxygen saturation and central venous oxygen
      saturation were assessed, including the difference between femoral venous oxygen
      saturation and central venous oxygen saturation.Despite significant correlation
      between obtained values of femoral venous oxygen saturation and central venous
      oxygen saturation (rs = 0.55; p < .001), the limits of agreement were wide in the
      control group (mean bias 2.7% +/- 7.9%; 95% limits of agreement -12.9% to 18.2%).
      In both the surgical and critically ill patients, limits of agreement (mean bias
      of -1.9% +/- 9.3%; 95% limits of agreement -20.0% to 16.3%, and mean bias of 4.6%
      +/- 14.3%; 95% limits of agreement -23.5% to 32.6%, respectively) were wide.
      Results for changes of femoral venous oxygen saturation and central venous oxygen
      saturation were similar. During initial treatment of critically ill patients, the
      difference between femoral venous oxygen saturation and central venous oxygen
      saturation including its range of variation diminished. CONCLUSION: There is lack
      of agreement between femoral venous oxygen saturation and central venous oxygen
      saturation in both stable and unstable medical conditions. Thus, femoral venous
      oxygen saturation should not be used as surrogate for central venous oxygen
      saturation.

PMID- 23168612
TI  - Diffusion tensor imaging and fiber tractography for the visualization of the
      female pelvic floor.
AB  - In the past decade, the evaluation of the pelvic support for understanding pelvic
      floor dysfunction by means of magnetic resonance imaging (MRI) has been an
      emerging area of research. Both static and dynamic MRI techniques have been
      effectively applied as a diagnostic resource to reveal abnormalities to the
      muscular pelvic support, but fail to unravel the precise pathophysiology of this
      complex disorder. Diffusion tensor imaging (DTI) and tractography comprise
      enhanced MRI techniques that enable the three-dimensional visualization of
      anisotropic tissue, such as muscle fibers, and provide a quantitative description
      of tissue organization and integrity. Quantifying DTI and fiber tractography
      might be able to reveal microstructural abnormalities in the pelvic support that
      are not noticeable using conventional MRI techniques. In this article, we discuss
      relevant anatomy, the current state of DTI and tractography in the evaluation of
      the female pelvic floor, and their potential future clinical applications.

PMID- 23168613
TI  - Direct binding of Grb2 has an important role in the development of
      myeloproliferative disease induced by ETV6/FLT3.

PMID- 23168614
TI  - Acute lymphoblastic leukemia associated with RCSD1-ABL1 novel fusion gene has a
      distinct gene expression profile from BCR-ABL1 fusion.

PMID- 23168615
TI  - Regioselective palladium-catalyzed olefination of coumarins via aerobic oxidative
      Heck reactions.
AB  - Pd-catalyzed oxidative Heck reactions of coumarins were developed via
      simultaneous C-H functionalization at the C3 position of coumarins under aerobic
      conditions.

PMID- 23168616
TI  - 3-Hydroxyflavones vs. 3-hydroxyquinolinones: structure-activity relationships and
      stability studies on Ru(II)(arene) anticancer complexes with biologically active
      ligands.
AB  - Ru(II)(eta(6)-arene) complexes, especially with bioactive ligands, are considered
      to be very promising compounds for anticancer drug design. We have shown recently
      that Ru(II)(eta(6)-p-cymene) complexes with 3-hydroxyflavone ligands exhibit very
      high in vitro cytotoxic activities correlating with a strong inhibition of
      topoisomerase IIalpha. In order to expand our knowledge about the structure
      activity relationships and to determine the impact of lipophilicity of the arene
      ligand and of the hydrolysis rate on anticancer activity, a series of novel 3
      hydroxyflavone derived Ru(II)(eta(6)-arene) complexes were synthesised.
      Furthermore, the impact of the heteroatom in the bioactive ligand backbone was
      studied by comparing the cytotoxic activity of Ru(II)(eta(6)-p-cymene) complexes
      of 3-hydroxyquinolinone ligands with that of their 3-hydroxyflavone analogues. To
      better understand the behaviour of these Ru(II) complexes in aqueous solution,
      the stability constants and pK(a) values for complexes and the corresponding
      ligands were determined. Furthermore, the interaction with the DNA model 5'-GMP
      and with a series of amino acids was studied in order to identify potential
      biological target structures.

PMID- 23168617
TI  - Label-free imaging characteristics of colonic mucinous adenocarcinoma using
      multiphoton microscopy.
AB  - Colorectal carcinoma (CRC) has high mortality and increased incidence rates. An
      early detection of CRC is very important. Multiphoton microscopy (MPM) with high
      resolution and high sensitivity is used to effectively distinguish the
      microstructure changes of normal and mucinous adenocarcinoma slices of ex vivo
      human colonic tissues. In mucinous adenocarcinoma mucosa, the glands are
      distorted and elongated, the gland cavity is indistinct, and the mesh collagen
      fibers are diminished. In the submucosa, the collagens are seriously disordered,
      elongated, pushed aside, and sparsely visible, the content of elastic fibers is
      also broken and almost disappearing. Many cancer cells, some in cavity-like shape
      full of mucus surrounded by some collagen fibers, occupied the submucosa, which
      are comparable to hematoxylin-eosin (HE) stained images. Second harmonic
      generation and two-photon excitation fluorescence (SHG/TPEF) intensity ratio can
      be used further to quantitatively evaluate normality and abnormality. The fast
      Fourier transform (FFT) images show that the normal collagen fibrils are dense
      and in random order, and the cancerous collagen is certainly organized. The
      exploratory results show that it has potential for the development of multiphoton
      mini-endoscopy in real-time early diagnosis of CRC.

PMID- 23168618
TI  - Biochemical measurements on single erythroid progenitor cells shed light on the
      combinatorial regulation of red blood cell production.
AB  - Adult bone marrow (BM) erythrocyte colony-forming units (CFU-Es) are important
      cellular targets for the treatment of anemia and also for the manufacture of red
      blood cells (RBCs) ex vivo. We obtained quantitative biochemical measurements
      from single and small numbers of CFU-Es by isolating and analyzing c
      Kit(+)CD71(high)Ter119(-) cells from adult mouse BM and this allowed us to
      identify two mechanisms that can be manipulated to increase RBC production. As
      expected, maximum RBC output was obtained when CFU-Es were stimulated with a
      combination of Stem Cell Factor (SCF) and Erythropoietin (EPO) mainly because SCF
      supports a transient CFU-E expansion and EPO promotes the survival and terminal
      differentiation of erythroid progenitors. However, we found that one of the main
      factors limiting the output in RBCs was that EPO induces a downregulation of c
      Kit expression which limits the transient expansion of CFU-Es. In the presence of
      SCF, the EPO-mediated downregulation of c-Kit on CFU-Es is delayed but still
      significant. Moreover, treatment of CFU-Es with 1-Naphthyl PP1 could partially
      inhibit the downregulation of c-Kit induced by EPO, suggesting that this process
      is dependent on a Src family kinase, v-Src and/or c-Fyn. We also found that CFU-E
      survival and proliferation was dependent on the level of time-integrated
      extracellular-regulated kinase (ERK) activation in these cells, all of which
      could be significantly increased when SCF and EPO were combined with mouse fetal
      liver-derived factors. Taken together, these results suggest two novel molecular
      strategies to increase RBC production and regeneration.

PMID- 23168619
TI  - Pilot-scale demonstration of the hybrid zero-valent iron process for treating
      flue-gas-desulfurization wastewater: part II.
AB  - The hybrid zero-valent-iron (hZVI) process is a novel chemical treatment process
      that has shown promise for removing heavy metals and nutrients from industrial
      wastewaters. In this study, a pilot-scale demonstration was conducted to
      continuously treat 3.8-7.6 L/min (1-2 gpm) of the flue-gas-desulfurization (FGD)
      wastewater at a coal-fired power plant for 5 months. In this paper, a spike test
      was conducted to evaluate performance of the hZVI process for removing selected
      toxic metals at artificially elevated concentrations. The results showed that a
      multiple-stage hZVI process could decrease selenate-Se from 22 mg/L to ~10 MUg/L
      and dissolved Hg(2+) from 1.15 mg/L to ~10 ng/L. In addition, the process
      simultaneously removed a broad spectrum of heavy metals such as As(III), As(V),
      Cr(VI), Cd(II), Pb(II) and Cu(II) from mg/L to near or sub-ppb (MUg/L) level
      after a single-stage treatment. The process consumed about 0.3 kg ZVI per 1 m(3)
      FGD wastewater treated at a cost of about US$0.6/m(3). Solid waste production and
      energy consumption were reasonably low. The successful pilot study demonstrated
      that the hZVI technology can be a low-cost, high-performance treatment platform
      for solving some of the toughest heavy metal water problems.

PMID- 23168620
TI  - Study on the determination of heavy metals in water samples with ultrasound
      assisted dispersive liquid-liquid microextraction prior to FAAS.
AB  - A new, simple and rapid method based on dispersive liquid-liquid microextraction
      (DLLME) was developed for extracting and preconcentrating copper (Cu), nickel
      (Ni), lead (Pb) and cadmium (Cd) in water samples prior to flame atomic
      absorption spectrometry (FAAS) analysis. 1-(2-thiazolylazo)-naphthol (TAN) was
      used as chelating reagents, and non-ionic surfactant Triton X-114 and CCl(4) as
      disperser solvent and extraction solvent, respectively. Some influential factors
      relevant to DLLME, such as the concentration of TAN, type and volume of disperser
      and extraction solvent, pH and ultrasound time, were optimized. Under the optimal
      conditions, the calibration curve was linear in the range of 10-800 MUg L(-1) for
      Cu and Ni, 10-500 MUg L(-1) for Pb, and 10-1,000 MUg L(-1) for Cd, respectively.
      The limits of detection for the four metal ions were below 0.5 MUg L(-1), with
      the enhancement factors of 105, 66, 28 and 106 for Cu, Ni, Pb and Cd,
      respectively. The relative standard deviations (RSD, n = 6) were 2.6-4.1%. The
      proposed method was applied to determination of Cu, Ni, Pb and Cd in water
      samples and satisfactory relative recoveries (93.0-101.2%) were achieved.

PMID- 23168621
TI  - Removal of ZnO nanoparticles in simulated wastewater treatment processes and its
      effects on COD and NH(4)(+)-N reduction.
AB  - For many engineered nanoparticles, the primary pathway of release into the
      environment is via sewage and industrial wastewater discharges. In this work, the
      removal of uncoated ZnO nanoparticles (ZnO NPs) during simulated wastewater
      treatment processes and its impact on treatment performance were examined.
      Simulated primary clarification removed the majority (about 70%) of the dosed ZnO
      NPs. During simulated sequencing batch reactor (SBR) processes, ZnO NPs were
      completely removed in each cycle throughout the 11-day experimental duration (two
      cycles per day). Continuous input of ZnO NPs into the wastewater (at
      concentrations up to 5 mg L(-1)) did not reduce chemical oxygen demand (COD)
      removal. NH(4)(+)-N removal was reduced at a dosing concentration of 5 mg L(-1)
      ZnO NPs per cycle. Inhibition of respiration of nitrifying microorganisms by ZnO
      NPs corroborated the reduction of NH(4)(+)-N removal. These results indicate that
      if the wastewater is treated, the release of ZnO NPs into receiving water bodies
      would be minimal and ZnO NPs would mainly accumulate in biosolids. Uncoated ZnO
      NPs in wastewater at very high concentrations may have some adverse effects on
      activated sludge process.

PMID- 23168622
TI  - Attributiveness of a mass flow analysis model for integrated water resources
      assessment under data-scarce conditions.
AB  - Nutrients in river systems originate from multiple emission sources, follow
      various pathways, and are subject to processes of conversion and fate. One
      approach to tackle this complexity is to apply balance-oriented models. Although
      these models operate on a coarse temporal and spatial scale, they are capable of
      assessing the significance of the different emission sources and their results
      can be the basis for developing integrated water quality management schemes. In
      this paper we propose and apply a methodology to evaluate the attributiveness of
      such model results with regard to the modelled emission pathways. The MONERIS
      (MOdelling Nutrient Emissions in RIver Systems) model is set up, assuming
      plausible ranges of emission levels from four principal sources. The sensitivity
      of model performance is computed and related to the contribution from the
      pathways. The approach is applied for a case study in the upper Western Bug
      catchment (Ukraine). Coefficient of determination (R(2)) is found insensitive
      against the model assumptions, at levels around 0.65 for nitrogen and 0.55 for
      phosphorous emissions. Relative mean absolute error is minimized around 0.2 for
      both nutrients, but with equifinal combinations of the varied emission pathways.
      Model performance is constrained by the ranges of the emission assumptions to a
      limited extent only.

PMID- 23168623
TI  - Cultivation of microalgae (Oscillatoria okeni and Chlorella vulgaris) using
      tilapia-pond effluent and a comparison of their biomass removal efficiency.
AB  - The uptake of dissolved nutrients by microalgae is the primary way to remove
      nitrogen in aquaculture systems. Many authors have studied the use of microalgae
      to treat wastewater from aquaculture. However, excessive microalgae accumulation
      may cause high levels of organic matter and suspended solids in the final
      effluent. Thus, an efficient way to remove excess algae is needed in wastewater
      treatment. In this study, the potential of the filamentous cyanobacterium,
      Oscillatoria okeni, and the green alga, Chlorella vulgaris, to remove nitrate
      nitrogen from tilapia-pond effluent was assessed. The results indicated that C.
      vulgaris exhibited higher specific rate of growth and rate of nitrate utilization
      than O. okeni. However, O. okeni has the advantage over C. vulgaris in solid
      liquid separation by filtration and sedimentation after treatment.

PMID- 23168624
TI  - Field performance of self-siphon sediment cleansing set for sediment removal in
      deep CSO chamber.
AB  - This paper presents a study of the self-siphon sediment cleansing set (SSCS), a
      system designed to remove sediment from the deep combined sewer overflow (CSO)
      chamber during dry-weather periods. In order to get a better understanding of the
      sediment removal effectiveness and operational conditions of the SSCS system, we
      carried out a full-scale field study and comparison analysis on the sediment
      depth changes in the deep CSO chambers under the conditions with and without the
      SSCS. The field investigation results demonstrated that the SSCS drains the dry
      weather flow that accumulated for 50-57 min from the sewer channel to the
      intercepting system in about 10 min. It is estimated that the bed shear stress in
      the CSO chamber and sewer channel is improved almost 25 times on average. The
      SSCS acts to remove the near bed solids with high pollution load efficiently.
      Moreover, it cleans up not only the new sediment layer but also part of the
      previously accumulated sediment.

PMID- 23168625
TI  - Effect of preparation conditions and washing of activated carbon from paper mill
      sewage sludge on its adsorptive properties.
AB  - Sludge-based activated carbon (SAC) was prepared from paper mill sewage sludge by
      physical activation with steam for wastewater treatment in this study. The
      effects of preparation variables, including carbonization temperature,
      carbonization time, activation temperature and activation time, on iodine number
      and yield were investigated through orthogonal experiments. The influences of
      washing by deionized water and acid on the characteristics and adsorption
      capacities of SAC for phosphate, methylene blue and reactive red 24 were also
      studied. The results indicated that the optimal preparation conditions were:
      carbonization temperature of 350  degrees C, carbonization time of 40 min,
      activation temperature of 800  degrees C and activation time of 20 min. The
      characteristics and adsorption capacities of SAC were obviously different before
      and after washing, especially by acid. The surface area was improved and
      adsorption capacities for dyes increased after washing, while adsorption capacity
      for phosphate decreased. The maximum adsorption capacities provided strong
      evidence of the potential of SAC as an alternative adsorbent for wastewater
      treatment.

PMID- 23168626
TI  - The hydrolysis and biogas production of complex cellulosic substrates using three
      anaerobic biomass sources.
AB  - In this study, the ability of various sludges to digest a diverse range of
      cellulose and cellulose-derived substrates was assessed at different temperatures
      to elucidate the factors affecting hydrolysis. For this purpose, the biogas
      production was monitored and the specific biogas activity (SBA) of the sludges
      was employed to compare the performance of three anaerobic sludges on the
      degradation of a variety of complex cellulose sources, across a range of
      temperatures. The sludge with the highest performance on complex substrates was
      derived from a full-scale bioreactor treating sewage at 37  degrees C. Hydrolysis
      was the rate-limiting step during the degradation of complex substrates. No
      activity was recorded for the synthetic cellulose compound carboxymethylcellulose
      (CMC) using any of the sludges tested. Increased temperature led to an increase
      in hydrolysis rates and thus SBA values. The non-granular nature of the
      mesophilic sludge played a positive role in the hydrolysis of solid substrates,
      while the granular sludges proved more effective on the degradation of soluble
      compounds.

PMID- 23168627
TI  - Simultaneous precipitation of phosphorus in a kraft pulp mill wastewater
      treatment plant.
AB  - Simultaneous precipitation (SP) using iron sulfates in the secondary treatment of
      elemental chlorine-free (ECF) kraft pulp mill wastewater was studied. In short
      term pilot plant studies phosphorus reduction was improved from 58% up to 81% by
      adding 10 mg(Fe)/L ferrous sulfate in the activated sludge (AS) process. The
      phosphorus reduction in full-scale experiment was about 80% when less than 10
      mg(Fe)/L was fed in with the influent of the AS plant. The reduction of
      phosphorus decreased with the dose of iron during the three month experiment. No
      notable change in either chemical oxygen demand (COD) or adsorbable organic
      halogen (AOX) reduction nor in the properties of sludge settling were observed
      during this SP experiment. Furthermore, no problems in sludge treatment due to
      increased iron concentrations in the waste sludge were reported. SP offers a
      simple way to decrease phosphorus discharges from AS plants instead of reliance
      on more expensive tertiary treatments.

PMID- 23168628
TI  - Preparation and adsorption properties of dialdehyde 8-aminoquinoline starch.
AB  - Dialdehyde 8-aminoquinoline starch (DASQA) was synthesized by the reaction of
      dialdehyde starch (DAS) and 8-aminoquinoline and was used to adsorb various ions
      from aqueous solution. DASQA was characterized by Fourier transform infrared (FT
      IR) spectra, thermogravimetric analysis, X-ray diffraction analysis. The
      adsorption properties of the polymer for Pb(2+), Cu(2+), Cd(2+), Ni(2+), and
      Zn(2+) were investigated. The result of the experiment reveals that the
      adsorption for Cd(2+) and Zn(2+)were approximately 2.51 mmol/g, 2.17 mmol/g,
      followed by Pb(2+) 1.93 mmol/g, Ni(2+) 1.66 mmol/g, Cu(2+) 1.19 mmol/g.
      Furthermore, the kinetic experiments indicated that the adsorption of DASQA for
      the above metal ions achieved equilibrium within 2 h. Therefore, DASQA is an
      effective adsorbent for the removal of different heavy metal ions from industrial
      waste solutions.

PMID- 23168629
TI  - Precipitation of heavy metals from coal ash leachate using biogenic hydrogen
      sulfide generated from FGD gypsum.
AB  - Investigations were undertaken to utilize flue gas desulfurization (FGD) gypsum
      for the treatment of leachate from the coal ash (CA) dump sites. Bench-scale
      investigations consisted of three main steps namely hydrogen sulfide (H(2)S)
      production by sulfate reducing bacteria (SRB) using sulfate from solubilized FGD
      gypsum as the electron acceptor, followed by leaching of heavy metals (HMs) from
      coal bottom ash (CBA) and subsequent precipitation of HMs using biologically
      produced sulfide. Leaching tests of CBA carried out at acidic pH revealed the
      existence of several HMs such as Cd, Cr, Hg, Pb, Mn, Cu, Ni and Zn. Molasses was
      used as the electron donor for the biological sulfate reduction (BSR) process
      which produced sulfide rich effluent with concentration up to 150 mg/L. Sulfide
      rich effluent from the sulfate reduction process was used to precipitate HMs as
      metal sulfides from CBA leachate. HM removal in the range from 40 to 100% was
      obtained through sulfide precipitation.

PMID- 23168630
TI  - Adsorptive removal of sulfonamide antibiotics in livestock urine using the high
      silica zeolite HSZ-385.
AB  - The adsorptive removal of seven sulfonamide antibiotics using the high-silica
      zeolite HSZ-385 from distilled water, synthetic urine and real porcine urine was
      investigated. The pH greatly affected the adsorption efficiency, and the amounts
      of all sulfonamide antibiotics adsorbed on HSZ-385 decreased at alkaline
      conditions compared with that at neutral conditions. During storage, the pH and
      ammonium-ion concentration increased with urea hydrolysis for porcine urine. We
      clarified that the adsorption efficiency of sulfonamides in synthetic urine was
      equivalent to that in distilled water, suggesting that adsorption behavior was
      not affected by coexistent ions. HSZ-385 could adsorb sulfonamide antibiotics in
      real porcine urine even though the non-purgeable organic carbon concentration of
      porcine urine was 4-7 g/L and was two orders of magnitude higher than those of
      sulfonamides (10 mg/L each). Moreover, the adsorption of sulfonamides reached
      equilibrium within 15 min, suggesting that HSZ-385 is a promising adsorbent for
      removing sulfonamides from porcine urine.

PMID- 23168631
TI  - Biogas desulfurization and biogas upgrading using a hybrid membrane system-
      modeling study.
AB  - Membrane gas permeation using glassy membranes proved to be a suitable method for
      biogas upgrading and natural gas substitute production on account of low energy
      consumption and high compactness. Glassy membranes are very effective in the
      separation of bulk carbon dioxide and water from a methane-containing stream.
      However, the content of hydrogen sulfide can be lowered only partially. This work
      employs process modeling based upon the finite difference method to evaluate a
      hybrid membrane system built of a combination of rubbery and glassy membranes.
      The former are responsible for the separation of hydrogen sulfide and the latter
      separate carbon dioxide to produce standard-conform natural gas substitute. The
      evaluation focuses on the most critical upgrading parameters like achievable gas
      purity, methane recovery and specific energy consumption. The obtained results
      indicate that the evaluated hybrid membrane configuration is a potentially
      efficient system for the biogas processing tasks that do not require high methane
      recoveries, and allows effective desulfurization for medium and high hydrogen
      sulfide concentrations without additional process steps.

PMID- 23168632
TI  - Biological activity of bleached kraft pulp mill effluents before and after
      activated sludge and ozone treatments.
AB  - Eucalyptus bleached kraft pulp production, an important sector of the Brazilian
      national economy, is responsible for generating large volume, high pollutant load
      effluents, containing a considerable fraction of recalcitrant organic matter. The
      objectives of this study were to quantify the biological activity of the effluent
      from a eucalyptus bleached kraft pulp mill, characterize the nature of compounds
      responsible for biological activity and assess the effect of ozone treatment on
      its removal. Primary and secondary effluents were collected bimonthly over the
      course of one year at a Brazilian bleached eucalypt kraft pulp mill and their
      pollutant loads (biochemical oxygen demand (BOD), chemical oxygen demand (COD),
      total organic carbon (TOC), adsorbable organic halogen (AOX), lignin,
      extractives) and biological activity (acute and chronic toxicity and estrogenic
      activity) quantified. The effluent studied did not present acute toxicity to
      Daphnia, but presented the chronic toxicity effects of algal growth inhibition
      and reduced survival and reproduction in Ceriodaphnia, as well as estrogenic
      activity. Chronic toxicity and estrogenic activity were reduced but not
      eliminated during activated sludge biological treatment. The toxicity
      identification evaluation revealed that lipophilic organic compounds (such as
      residual lignin, extractives and their byproducts) were responsible for the
      toxicity and estrogenic activity. Ozone treatment (50 mg/L O(3)) of the secondary
      effluent eliminated the chronic toxicity and significantly reduced estrogen
      activity.

PMID- 23168633
TI  - Long-term performance evaluation of EBPR process in tropical climate: start-up,
      process stability, and the effect of operational pH and influent C:P ratio.
AB  - To date, little information is known about the operation of the enhanced
      biological phosphorus removal (EBPR) process in tropical climates. Along with the
      global concerns on nutrient pollution and the increasing array of local
      regulatory requirements, the applicability and compliance accountability of the
      EBPR process for sewage treatment in tropical climates is being evaluated. A
      sequencing batch reactor (SBR) inoculated with seed sludge from a conventional
      activated sludge (CAS) process was successfully acclimatized to EBPR conditions
      at 28  degrees C after 13 days' operation. Enrichment of Candidatus
      Accumulibacter phosphatis in the SBR was confirmed through fluorescence in situ
      hybridization (FISH). The effects of operational pH and influent C:P ratio on
      EBPR were then investigated. At pH 7 or pH 8, phosphorus removal rates of the
      EBPR processes were relatively higher when operated at C:P ratio of 3 than C:P
      ratio of 10, with 0.019-0.020 and 0.011-0.012 g-P/g-MLVSS*day respectively. One
      year operation of the 28  degrees C EBPR process at C:P ratio of 3 and pH 8
      demonstrated stable phosphorus removal rate of 0.020 +/- 0.003 g-P/g-MLVSS*day,
      corresponding to effluent with phosphorus concentration <0.5 mg/L. This study
      provides the first evidence on good EBPR activity at relatively high temperature,
      indicating its applicability in a tropical climate.

PMID- 23168634
TI  - An approximate solution for two-dimensional groundwater infiltration in sewer
      systems.
AB  - Estimating groundwater infiltration into sewer systems is important for
      wastewater treatment operators and municipalities. This paper presents an
      approximate solution for steady-state groundwater infiltration into sewer systems
      through line defects. The groundwater table was assumed to be horizontal and the
      aquifer homogeneous and isotropic. Mobius transformation technique and equivalent
      circumference method were introduced to solve the governing equation. The
      infiltration rate is found to be controlled by the hydraulic conductivity of the
      surrounding soil, the total hydraulic head above the sewer pipe, the size of the
      sewer pipe, the position of the defect, and the size of the defect.

PMID- 23168635
TI  - Analysis of chemical reaction kinetics of depredating organic pollutants from
      secondary effluent of wastewater treatment plant in constructed wetlands.
AB  - Four subsurface constructed wetlands were built to treat the secondary effluent
      of a wastewater treatment plant in Tangshan, China. The chemical pollutant
      indexes of chemical oxygen demand (COD) were analyzed to evaluate the removal
      efficiency of organic pollutants from the secondary effluent of the wastewater
      treatment plant. In all cases, the subsurface constructed wetlands were efficient
      in treating organic pollutants. Under the same hydraulic loading condition, the
      horizontal flow wetlands exhibited better efficiency of COD removal than vertical
      flow wetlands: the removal rates in horizontal flow wetlands could be maintained
      at 68.4 +/- 2.42% to 92.2 +/- 1.61%, compared with 63.8 +/- 1.19% to 85.0 +/-
      1.25% in the vertical flow wetlands. Meanwhile, the chemical reaction kinetics of
      organic pollutants was analyzed, and the results showed that the degradation
      courses of the four subsurface wetlands all corresponded with the first order
      reaction kinetics to a large extent.

PMID- 23168636
TI  - Immobilization of magnesium ammonium phosphate crystals within microchannels for
      efficient ammonia removal.
AB  - Magnesium ammonium phosphate was formed in flow-through microchannels of silica
      monoliths using two different methods to fabricate materials that show efficient
      ammonia adsorption performance from wastewater with low hydraulic resistance.
      Magnesium ammonium phosphate crystals in these materials release ammonia when
      heated at 378 K, yielding primarily magnesium hydrogen phosphate. When this
      material was used for ammonia removal from an aqueous solution containing 100 ppm
      ammonia in a flow system, the material readily removed ammonia, decreasing the
      ammonia concentration to 25 ppm. The material can be reactivated by the same
      procedure and used again for ammonia removal. Hydrodynamic resistance through the
      lengths of the materials depend on the shape of the immobilized crystals, showing
      that needle-like crystals are more effective to cause less resistance than plate
      like particles. The material containing needle-like crystals causes only
      approximately one-eighth of the hydraulic resistance that a packed column
      consisted of spherical particles with a typical bed porosity of 0.5 does. Thus,
      these results demonstrate the high applicability of the material for ammonia
      removal from wastewater in a continuous process.

PMID- 23168637
TI  - Fate of pathogen indicators in a domestic blend of food waste and wastewater
      through a two-stage anaerobic digestion system.
AB  - Anaerobic digestion is a viable on-site treatment technology for rich organic
      waste streams such as food waste and blackwater. In contrast to large-scale
      municipal wastewater treatment plants which are typically located away from the
      community, the effluent from any type of on-site system is a potential pathogenic
      hazard because of the intimacy of the system to the community. The native
      concentrations of the pathogen indicators Escherichia coli, Clostridium
      perfringens and somatic coliphage were tracked for 30 days under stable operation
      (organic loading rate (OLR) = 1.8 kgCOD m(-3) day(-1), methane yield = 52% on a
      chemical oxygen demand (COD) basis) of a two-stage laboratory-scale digester
      treating a mixture of food waste and blackwater. E. coli numbers were reduced by
      a factor of 10(6.4) in the thermophilic stage, from 10(7.5+/-0.3) to 10(1.1+/
      0.1) cfu 100 mL(-1), but regenerated by a factor of 10(4) in the mesophilic
      stage. Neither the thermophilic nor mesophilic stages had any significant impact
      on C. perfringens concentrations. Coliphage concentrations were reduced by a
      factor of 10(1.4) across the two stages. The study shows that anaerobic digestion
      only reduces pathogen counts marginally but that counts in effluent samples could
      be readily reduced to below detection limits by filtration through a 0.22 um
      membrane, to investigate membrane filtration as a possible sanitation technique.

PMID- 23168638
TI  - Effect of ionizing radiation on antioxidant compounds present in cork wastewater.
AB  - A preliminary study of the gamma radiation effects on the antioxidant compounds
      present in cork cooking water was carried out. Radiation studies were performed
      using radiation between 20 and 50 kGy at 0.4 and 2.4 kGy h(-1). The radiation
      effects on organic matter content were evaluated by chemical oxygen demand. The
      antioxidant activity was measured by ferric reducing power assay. The total
      phenolic content was studied using the Folin-Ciocalteau method. Results show that
      gamma radiation increases both the amount of phenolic compounds and antioxidant
      capacity of cork cooking water. These results highlight the potential of this
      technology for increasing the added value of cork waters.

PMID- 23168639
TI  - Number of residual thermotolerant coliforms on plants and in soil when using
      reclaimed domestic wastewater for irrigation.
AB  - The reclamation of domestic wastewater for irrigation is one alternative approach
      to solve the water scarcity crisis, but it is essential to control the
      microbiological quality of wastewater used for irrigation. The removal of
      thermotolerant coliforms, also known as faecal coliforms (FC), from treated
      domestic wastewater by intermittent media infiltration (IMI) in column was
      studied. The columns were filled with natural filter media (soil, soil/charcoal
      and zinc-modified zeolite, Zeo-Zn), and wastewater, IMI-treated wastewater and
      disinfected wastewater were compared. The numbers of residual FC on Swiss chard
      (Beta vulgaris) and in agricultural soil were determined over a 4-month period.
      The column using Zeo-Zn had a higher FC removal efficiency (2.98 log) than
      columns with other filter media and disinfection (1.87-2.57 log) due to the
      bactericidal properties of Zn(2+). The treatment of wastewater using Zeo-Zn and
      disinfection both decreased the accumulation of FC on plants and in soil to
      approximately 1-20 MPN/g dry matter. IMI-treated wastewater using the column with
      Zeo-Zn was suitable for unrestricted agricultural use, complied with Mexican
      regulations (as did disinfected wastewater) and had a low risk of FC
      contamination of plants and soil.

PMID- 23168640
TI  - Comparative and integrative environmental assessment of advanced wastewater
      treatment processes based on an average removal of pharmaceuticals.
AB  - Pharmaceuticals are normally barely removed by conventional wastewater
      treatments. Advanced technologies as a post-treatment, could prevent these
      pollutants reaching the environment and could be included in a centralized
      treatment plant or, alternatively, at the primary point source, e.g. hospitals.
      In this study, the environmental impacts of different options, as a function of
      several advanced treatments as well as the centralized/decentralized
      implementation options, have been evaluated using Life Cycle Assessment (LCA)
      methodology. In previous publications, the characterization of the toxicity of
      pharmaceuticals within LCA suffers from high uncertainties. In our study, LCA was
      therefore only used to quantify the generated impacts (electricity, chemicals,
      etc.) of different treatment scenarios. These impacts are then weighted by the
      average removal rate of pharmaceuticals using a new Eco-efficiency Indicator EFI.
      This new way of comparing the scenarios shows significant advantages of upgrading
      a centralized plant with ozonation as the post-treatment. The decentralized
      treatment option reveals no significant improvement on the avoided environmental
      impact, due to the comparatively small pollutant load coming from the hospital
      and the uncertainties in the average removal of the decentralized scenarios. When
      comparing the post-treatment technologies, UV radiation has a lower performance
      than both ozonation and activated carbon adsorption.

PMID- 23168641
TI  - Verification of equations for incipient motion studies for a rigid rectangular
      channel.
AB  - The current study aims to verify the existing equations for incipient motion for
      a rigid rectangular channel. Data from experimental work on incipient motion from
      a rectangular flume with two different widths, namely 0.3 and 0.6 m, were
      compared with the critical velocity value predicted by the equations of Novak &
      Nalluri and El-Zaemey. The equation by El-Zaemey performed better with an average
      discrepancy ratio value of 1.06 compared with the equation by Novak & Nalluri
      with an average discrepancy ratio value of 0.87. However, as the sediment deposit
      thickness increased, the equation by El-Zaemey became less accurate. A plot on
      the Shields Diagram using the experimental data had shown the significant effect
      of the sediment deposit thickness where, as the deposit becomes thicker, the
      dimensionless shear stress theta value also increased. A new equation had been
      proposed by incorporating the sediment deposit thickness. The new equation gave
      improved prediction with an average discrepancy ratio value of 1.02.

PMID- 23168642
TI  - Electrocoagulation of synthetic dairy wastewater.
AB  - This study compares the effectiveness of pollutant removal from synthetic dairy
      wastewater electrocoagulated by means of aluminum and iron anodic dissolution. A
      method based on the cubic function (third degree polynomial) was proposed for
      electrocoagulant dosing. Mathematical methods for calculating the optimal
      electrocoagulant doses proved to be quite precise and useful for practical
      applications. The results of gravimetric measurements of electrocoagulant
      (electrode) consumption demonstrated that theoretical doses of Al determined
      based on Faraday's law were substantially lower than those produced by electrode
      weighing. The above phenomenon was also discussed in the light of the results of
      polarization resistance measurements for Al and Fe electrodes used in the study.

PMID- 23168643
TI  - Anaerobic digestion of sunflower oil cake: a current overview.
AB  - Due to the chemical and physical structure of a lignocellulosic biomass, its
      anaerobic digestion (AD) is a slow and difficult process. In this paper, the
      results obtained from a batch biochemical methane potential (BMP) test and fed
      batch mesophilic AD assays of sunflower oil cake (SuOC) are presented. Taking
      into account the low digestibility shown during one-stage experiments the methane
      yield decreased considerably after increasing the organic loading rate (OLR) from
      2 to 3 g VS L(-1) d(-1), SuOC was subjected to a two-stage AD process (hydrolytic
      acidogenic and methanogenic stages), in two separate reactors operating in series
      where the methanogenic stage became acidified (with >1,600 mg acetic acid L(-1))
      at an OLR as low as 2 g VS L(-1) d(-1). More recently, BMP assays were carried
      out after mechanical, thermal, and ultrasonic pre-treatments to determine the
      best option on the basis of the methane yield obtained.

PMID- 23168644
TI  - The effect of photosensitizer on diclofenac photodegradation under simulated
      sunlight.
AB  - This paper studies the effect of photosensitizer (acetone, H(2)O(2), surfactant
      and pigment) on photodegradation of diclofenac (DCF) under simulated sunlight.
      The results demonstrate that degradation pathways proceed via pseudo first-order
      kinetics in all cases. The photodegradation rate was found to increase with
      increasing acetone and H(2)O(2). Surfactant and pigment inhibited the
      photodegradation of DCF. Finally, four kinds of main degradation products were
      observed by high performance liquid chromatography/mass spectrometry and their
      chemical structures were suggested.

PMID- 23168645
TI  - An adaptive framework to differentiate receiving water quality impacts on a multi
      scale level.
AB  - The paradigm shift in recent years towards sustainable and coherent water
      resources management on a river basin scale has changed the subject of
      investigations to a multi-scale problem representing a great challenge for all
      actors participating in the management process. In this regard, planning
      engineers often face an inherent conflict to provide reliable decision support
      for complex questions with a minimum of effort. This trend inevitably increases
      the risk to base decisions upon uncertain and unverified conclusions. This paper
      proposes an adaptive framework for integral planning that combines several
      concepts (flow balancing, water quality monitoring, process modelling, multi
      objective assessment) to systematically evaluate management strategies for water
      quality improvement. As key element, an S/P matrix is introduced to structure the
      differentiation of relevant 'pressures' in affected regions, i.e. 'spatial
      units', which helps in handling complexity. The framework is applied to a small,
      but typical, catchment in Flanders, Belgium. The application to the real-life
      case shows: (1) the proposed approach is adaptive, covers problems of different
      spatial and temporal scale, efficiently reduces complexity and finally leads to a
      transparent solution; and (2) water quality and emission-based performance
      evaluation must be done jointly as an emission-based performance improvement does
      not necessarily lead to an improved water quality status, and an assessment
      solely focusing on water quality criteria may mask non-compliance with emission
      based standards. Recommendations derived from the theoretical analysis have been
      put into practice.

PMID- 23168646
TI  - Designing monitoring programs for chemicals of emerging concern in potable reuse-
      what to include and what not to include?
AB  - This study discussed a proposed process to prioritize chemicals for reclaimed
      water monitoring programs, selection of analytical methods required for their
      quantification, toxicological relevance of chemicals of emerging concern
      regarding human health, and related issues. Given that thousands of chemicals are
      potentially present in reclaimed water and that information about those chemicals
      is rapidly evolving, a transparent, science-based framework was developed to
      guide prioritization of which compounds of emerging concern (CECs) should be
      included in reclaimed water monitoring programs. The recommended framework
      includes four steps: (1) compile environmental concentrations (e.g., measured
      environmental concentration or MEC) of CECs in the source water for reuse
      projects; (2) develop a monitoring trigger level (MTL) for each of these
      compounds (or groups thereof) based on toxicological relevance; (3) compare the
      environmental concentration (e.g., MEC) to the MTL; CECs with a MEC/MTL ratio
      greater than 1 should be prioritized for monitoring, compounds with a ratio less
      than '1' should only be considered if they represent viable treatment process
      performance indicators; and (4) screen the priority list to ensure that a
      commercially available robust analytical method is available for that compound.

PMID- 23168647
TI  - Photochemical degradation of 4-chlorophenol in the aqueous phase using
      peroxyacetic acid (PAA).
AB  - The photochemical degradation of 4-chlorophenol (4-CP) using ultraviolet
      irradiation (UV) of 6, 12 and 18 W with peroxyacetic acid (PAA) was studied in a
      batch reactor. The objective of this work was to investigate degradation and
      mineralization of 4-CP by PAA. The degradation efficiency increased with
      increasing UV input. The degradation process was also pH and initial PAA
      concentration dependent. The optimum conditions for the photochemical degradation
      of 4-CP as UV input, pH and PAA concentration was found to be 18 W, 9.5 and 3,040
      ppm. The reaction efficiency decreased with increasing initial 4-CP
      concentrations. More than 95% mineralization of 4-CP was achieved with the UV/PAA
      process. The chloride ion concentration and chemical oxygen demand (COD) was
      evaluated. The chloride ion concentration and COD were decreased gradually with
      increasing UV input. Samples were analyzed by high pressure liquid chromatography
      (HPLC), UV spectrophotometry and gas chromatography-mass spectrometry (GC-MS) for
      residual concentration and identification of final degraded products.

PMID- 23168648
TI  - Can stormwater harvesting restore pre-development flows in urban catchments in
      South East Queensland?
AB  - Increases in the impervious area due to urbanisation have been shown to have
      negative impacts on the physical and ecological condition of streams, primarily
      through increased volume and frequency of runoff. The harvesting and detention of
      runoff has a potential to decrease this impact. This paper describes the effects
      of urbanisation on catchment flow and of stormwater harvesting on reducing those
      adverse impacts on a stream in South East Queensland (SEQ), Australia. A largely
      undeveloped catchment located southeast of Brisbane city was calibrated and
      validated using the Stormwater Management Model (SWMM). This model was used to
      investigate the effect of a range of future increases in urbanisation
      (represented by impervious area) on stream hydrology as well as the potential of
      stormwater harvesting to return the catchments to predevelopment flow conditions.
      Stormwater harvesting was modelled according to flow frequency measures specified
      in current SEQ development guidelines. These guidelines stipulate the capture of
      the first 10 mm of runoff from impervious areas of 0-40% and the first 15 mm from
      impervious areas of 40% or greater for urban developments. We found that
      increases in the impervious area resulted in increases in the mean, frequency and
      duration of high flows, and an increase in the mean rate of rise and fall for
      storm events in the catchment. However, the predevelopment (non-urbanised) flow
      distribution was very flashy in comparison with all urbanised scenarios; i.e. it
      had the quickest response to rainfall indicated by a high rate of rise to and
      fall from peak flow volume, followed by a return to zero flow conditions.
      Capturing the runoff according to the development guidelines resulted in a
      reduction in flow towards the flow distribution of a lower impervious area,
      however this was insufficient to meet predevelopment conditions. This suggests a
      stronger influence of impervious areas in this catchment on the volume of runoff
      than flow frequency measures are able to ameliorate.

PMID- 23168649
TI  - Lateral manual asymmetries: a longitudinal study from birth to 24 months.
AB  - Longitudinal studies tracking the early development of manual asymmetries are
      fairly rare compared to the large number of studies assessing hand preference in
      infancy. Moreover, most prior longitudinal studies have performed behavioral
      observation over relatively short-time spans considering the celerity of early
      development. This study aims (i) to investigate the direction and consistency of
      manual lateral asymmetries over a longer period, from birth to 24 months of age,
      and (ii) to compare individual and group trajectories to better understand
      discrepancies between prior studies. Nineteen healthy infants were observed eight
      times in tasks that were adjusted progressively as infants manual skills
      developed. Results suggested two distinct periods in terms of the direction,
      strength, and consistency of manual preference. First, infants went through an
      initial phase characterized by a lack of lateral manual asymmetries. From 9
      months of age, however, group analyses revealed an emerging and steadily growing
      right lateral bias over time, while individual trajectories revealed that the
      group-level right-bias formed progressively from a background of highly
      fluctuating and highly variable developmental trajectories.

PMID- 23168650
TI  - Looking to our past to find the way forward for the american association of
      bronchology and interventional pulmonology.

PMID- 23168651
TI  - Flexible bronchoscopy without sedation: is less or none more when it comes to
      sedation?

PMID- 23168652
TI  - Tracheobronchial involvement as a sole manifestation of relapsing polychondritis.
AB  - STUDY OBJECTIVES: To report the clinical, imaging, and pathologic manifestations
      of case series of patients in whom the only systemic expression of relapsing
      polychondritis (RP) was their airway complications. DESIGN: Retrospective review
      of the medical records of all patients with respiratory complications of RP
      between 1995 and 2007. SETTING: Tertiary care, university-affiliated hospital.
      RESULTS: Three patients with RP had just lower airway manifestations as the only
      sign of their RP. All 3 were women, aged 44, 49, and 54 years. All had an
      abnormal chest computed tomography scan, although 2 had a completely normal chest
      x-ray. All had positive tracheal biopsy, which was consistent with the diagnosis
      of respiratory chondritis. Pulmonary function tests showed severe reduction in
      forced expiratory volume in 1 second in all patients. Bronchoscopy revealed
      tracheal narrowing with variable degrees of inflammation and collapsibility in
      all patients. Two of the 3 patients underwent tracheal and bronchial stent
      insertion. Pharmacotherapy included prednisone, methotrexate, cyclophosphamide,
      and leflunomide. The overall outcome was poor. Two patients died as a result of
      respiratory complications, 25 and 30 months from diagnoses, and 1 is still alive
      with follow-up of 85 months after presentation. CONCLUSIONS: Lower airway
      manifestations of RP can be the only sign of the disease. RP has to be considered
      in the differential diagnosis of patients with recent onset of progressive
      dyspnea and severe airflow limitation even without other systemic signs of
      cartilage damage.

PMID- 23168653
TI  - A feasibility and efficacy study on bronchoscopy with a virtual navigation
      system.
AB  - OBJECTIVE: The purpose of this study was to evaluate the diagnostic accuracy of
      bronchoscopy with virtual bronchoscopy (VB) navigation. PATIENTS AND METHODS:
      Forty-two consecutive patients with <=30-mm diameter peripheral pulmonary shadows
      or lesions that were difficult or impossible to identify on plain x-rays
      regardless of size were selected. Before bronchoscopy, multidetector computed
      tomography was performed, and VB images were created. Then, ultrathin
      bronchoscopy was carried out with VB navigation followed by conventional 4-mm
      diameter bronchoscopy. RESULTS: Thirty-seven patients were finally enrolled.
      There were 12 re-examination cases in which earlier conventional bronchoscopy was
      nondiagnostic. Diagnosis was established in 28 patients (25 malignant and 3
      benign lesions), with the diagnostic yield of 75.7% (sensitivity 86.2%,
      specificity 62.5%, positive predictive value 89.3%, negative predictive value
      55.6%, and accuracy 81.1%). The diagnostic yield for lesions of diameter <=20 mm,
      21 to 30 mm, and >=31 mm were 76.9%, 76.5%, and 71.4%, respectively, for all
      patients, and 90%, 84.6%, and 83.3%, respectively, for malignant cases. The
      diagnostic yield in patients who underwent re-examinations was 83.3% for all
      cases and 88.9% for malignant cases. Three patients had completely invisible
      shadows on x-ray fluoroscopy and all of these cases were diagnosed on
      bronchoscopy. No statistically significant difference was observed between the
      diagnostic yield for the different sizes, pathology, and number of bronchoscopies
      required. CONCLUSIONS: Bronchoscopy with VB navigation yielded high accuracy even
      for small peripheral pulmonary nodules and shadows that were difficult or
      impossible to identify on plain x-rays, even for patients in whom earlier
      conventional bronchoscopy was nondiagnostic.

PMID- 23168654
TI  - Diagnostic value of histology compared with cytology in transbronchial aspiration
      samples obtained by histology needle.
AB  - OBJECTIVE: Results from endoscopic needle aspiration [transbronchial needle
      aspiration (TBNA), esophageal ultrasound-guided fine needle aspiration, real-time
      endobronchial ultrasound] mainly rely on cytology. We performed a retrospective
      study to evaluate the possible advantage of obtaining histologic samples during
      TBNA in the diagnostic assessment of mediastinal lymph node enlargement.
      MATERIALS AND METHODS: In a retrospective study 2 pathologists evaluated all
      TBNAs from patients with mediastinal lymph node enlargement in whom
      representative histologic and cytologic material was obtained, using only a
      histology needle. Cytology was reviewed before histology in a randomized, blinded
      fashion. Afterward, the results were related to the diagnosis made in the actual
      workup of the patient. RESULTS: A total of 50 TBNAs were reviewed. In 86% (43 of
      50), both pathologists made the same diagnosis on both specimens, or a difference
      in cytology and/or histology specimens did not alter the eventual treatment. In
      14% (7 of 50) of all TBNAs, histology revealed a diagnosis according to at least
      1 pathologist, which altered patient treatment. CONCLUSIONS: Histologic material
      can reveal additional diagnostic information compared with sole cytologic
      examination in 14% of representative TBNA samples in patients with mediastinal
      lymph node enlargement. A discrepancy between cytologic and histologic TBNA
      results should prompt further investigation.

PMID- 23168655
TI  - Computed tomography measurements for airway stent insertion in malignant airway
      obstruction.
AB  - BACKGROUND: Metallic airway stents for malignant airway obstruction are
      considered safe, yet are not without complications. This study reviews the role
      of computed tomography (CT) airway measurements for planning stent placement in
      malignant airway obstruction before the actual therapeutic procedure to avoid
      invasive diagnostic evaluation before the stent placement and to reduce
      complications. METHODS: This study is a retrospective review of information from
      a stent order database and medical records of patients receiving stents for
      malignant airway obstruction at a university hospital over a 12-year period. CT
      scans were used to determine stent diameter by calculating mean diameters of
      healthy adjacent zones (proximal and distal), stent length (length of diseased
      airway), and location and number of potential stents. Results of CT planning
      before bronchoscopy were judged by complication rates. RESULTS: Patient
      population consisted of 69 patients, 61.7+/-14.0 years old, 40 males, in whom 92
      stents were inserted. The most frequent cause of airway obstructions was
      tracheobronchial cancer (32). All patients had nitinol stent placement; 66 stents
      were covered and 26 were uncovered. Follow-up time was 1 to 1067 days (median: 35
      days). Complication rate was 10.1% and mainly involved the patients with tracheal
      obstruction (6). Complications included stent fractures (2), migration (2),
      granuloma (1), and infectious tracheitis (2). One early death within 24 hours
      after the procedure was not related to stent placement. Five patients required
      follow-up therapeutic bronchoscopy to treat the complications. CONCLUSIONS: These
      results suggest that prestent planning by noninvasive method of obtaining CT scan
      provides optimal stent size and position, possibly avoiding a diagnostic
      bronchoscopy and reducing complications. Further prospective study is needed to
      confirm these results because of limitation of this study's design.

PMID- 23168656
TI  - Flexible bronchoscopy in supine or sitting position: a randomized prospective
      analysis of safety and patient comfort.
AB  - BACKGROUND: Flexible bronchoscopy is performed under many different conditions
      (sitting/supine position, with or without oxygen prophylaxis) in different
      hospitals according to local traditions. OBJECTIVES: The study was to investigate
      the effect of different patient positions in flexible bronchoscopy on patient
      comfort and safety. METHODS: We started a prospective randomized controlled trial
      to compare bronchoscopy in supine and sitting positions. Consecutive outpatients
      undergoing regular diagnostic bronchoscopy were included and randomly selected to
      be in a supine or sitting position. A self-administrated questionnaire was taken
      from the patients after the bronchoscopy and the answers were evaluated. A total
      of 107 patients were included; 46 underwent bronchoscopy in the supine position.
      RESULTS: Of all patients, 52% showed a decrease in oxygen saturation of more than
      4%. The sitting position is a risk factor for oxygen decline, with a relative
      risk of 2.46. CONCLUSIONS: We recommend performing the procedure while the
      patient is in a supine position. We also recommend routine prophylactic low-flow
      supplemental oxygen in all patients undergoing bronchoscopy.

PMID- 23168657
TI  - Nasolaryngoscopic validation of a set of clinical predictors of aspiration in a
      critical care setting.
AB  - BACKGROUND: Aspiration is frequent in patients with acute neurologic disorders
      and swallowing dysfunction. Its incidence in stroke, as high as 51%, increases
      mortality by up to 3 times. Pneumonia, its main complication, further increases
      morbidity, mortality, and patient care costs. The objective of this study was to
      evaluate a set of bedside predictors of aspiration ["wet voice," 3-oz water
      swallow test, and cervical auscultation in an intensive care unit (ICU)] and
      compare them with nasolaryngoscopy as the gold standard. METHODS: We conducted a
      prospective, nonblinded study of bedside predictors of aspiration risks in 65
      consecutive ICU patients with an acute neurologic disorder or a severe medical or
      surgical condition with decreased level of consciousness. RESULTS: Endoscopic
      aspiration was detected in 17 patients. Sensitivities for wet voice, 3-oz water
      swallow test, and cervical auscultation were 58.82%, 88.23%, and 82.35%;
      specificities were 78.26%, 62.50%, and 80.43%. Positive predictive values were
      50%, 45.45%, and 60.86%, and negative predictive values were 83.72%, 93.75%, and
      92.50%, respectively. Positive likelihood ratios were 2.70, 2.35, and 4.20,
      respectively. The association of 2 positive clinical predictors, wet voice and
      cervical auscultation or wet voice and 3-oz water swallow test, improved
      specificity to 92.85% and 84.61%, positive predictive values to 83.33% and
      69.23%, and likelihood ratios to 10.76 and 5.85, respectively. CONCLUSIONS:
      Bedside clinical predictors for aspiration risks are a useful screening tool for
      ICU patients presenting with risk factors for this complication.

PMID- 23168658
TI  - Bronchoscopic foreign body extraction in a pulmonary medicine department: a
      retrospective review of egyptian experience.
AB  - Foreign body (FB) removal in our hospital was almost exclusively performed by
      surgeons through a rigid bronchoscope until the pulmonologists started getting
      involved in FB extraction. This study aimed to retrospectively review the results
      of 2 years of experience with 120 patients who presented or were referred to the
      Pulmonary Medicine Department, Ain Shams University Hospital in Cairo, Egypt,
      with clinical suspicion of FB aspiration during the period between December 2006
      and December 2008. FBs were removed by either rigid and/or flexible bronchoscopy
      using either general or topical anesthesia. There were 54 male and 66 female
      patients with an age range between 3 months and 70 years and 68.5% of the
      patients were under the age of 10 years. Ninety patients (75%) presented with a
      definite history of FB aspiration, with a time interval between aspiration and
      presentation ranging between less than 6 hours and 12 months. The FB was visible
      on the chest x-ray in 42 cases. Aspirations were primarily into the right lung
      (53.2%). Seeds and scarf pins were the most common FB found, and were retrieved
      in 36 cases. Pulmonologists were successful in extracting 110 out of 111 (99.1%)
      bronchoscopically visualized FBs, and open thoracotomy was required in only 1
      case for FB removal. In another 6 cases, only mucous plug was found to be the
      endogenous FB, whereas no FB could be found in 3 cases. No mortality or serious
      complications took place during or after the bronchoscopy. In conclusion,
      pulmonologists can extract FBs easily and safely either by using rigid and/or
      flexible bronchoscopes if they have the appropriate experience.

PMID- 23168659
TI  - Tracheobronchial manifestations of aspergillosis.
AB  - OBJECTIVE: The purpose of this article is to describe 3 patients each of whom
      developed a different form of tracheobronchial aspergillosis. METHODS: We
      describe our clinical experience with 3 patients who developed significant
      respiratory symptoms secondary to Aspergillus infection. All patients were
      followed closely until there was resolution of pulmonary problems or they
      succumbed to respiratory insufficiency. RESULTS: The first patient had asthma and
      her clinical and bronchoscopic findings were compatible with the diagnosis of
      mucoid impaction syndrome caused by Aspergillus. Response to therapy was
      excellent with complete recovery. The second and third patients had what we
      believe was tracheobronchial pseudomembranous aspergillosis. The precise reason
      for this complication in the second patient is unknown. The third patient was
      immunosuppressed and developed tracheobronchial aspergillosis. Despite aggressive
      therapy, both of these patients died. Diagnostic bronchoscopy was helpful in
      detecting the airway abnormalities and for obtaining respiratory specimens for
      culture. CONCLUSIONS: These cases show the diverse tracheobronchial
      manifestations of Aspergillus species. Diagnostic bronchoscopy was helpful in the
      diagnosis of airway involvement by aspergillus.

PMID- 23168660
TI  - Tracheal ring herniation.
AB  - Inspection bronchoscopy during percutaneous dilational tracheostomy has become
      the standard of care to reduce complications of the procedure. During
      bronchoscopy, anatomic defects can be visualized before performing the procedure.
      We describe a case of discovering herniated tracheal rings in preprocedure
      bronchoscopy and subsequent treatment of this rare finding.

PMID- 23168661
TI  - Endobronchial fibroepithelial polyp.
AB  - Benign polypoid lesions are an uncommon finding on bronchoscopic examination. The
      histopathologic fibroepithelial subtype is very rare in this location. In this
      report, we describe a 77-year-old man diagnosed with a fibroepithelial polyp
      located at the bifurcation of the left main bronchus; this was completely removed
      using flexible bronchoscope.

PMID- 23168662
TI  - Spontaneous pneumomediastinum in a patient with facial rash.
AB  - A 38-year-old male nonsmoker presented with constitutional symptoms,
      polyarthritis, facial rash, and progressive dyspnea of more than 1-year duration.
      Chest radiology revealed bilateral reticular and ground glass infiltrates.
      Connective tissue disease investigation was unrevealing. Pulmonary function test
      was consistent with restrictive lung disease and decreased diffusion capacity.
      The patient was treated with corticosteroids for amyopathic dermatomyositis with
      no improvement of dyspnea. Flexible bronchoscopy was noncontributory. Four and 6
      months after initial presentation, he developed spontaneous pneumomediastinum and
      extensive subcutaneous emphysema that resolved with conservative therapy.
      Surgical lung biopsy revealed cellular-fibrotic nonspecific interstitial
      pneumonia for which he was started on cytotoxic medication, with no improvement
      in respiratory symptoms. The frequency of interstitial lung disease (ILD)-related
      polymyositis/dermatomyositis (DM) has been reported to range between 5% and 30%
      and nonspecific interstitial pneumonia is seen in up to 80% of DM-related ILD and
      in almost all the reported patients with amyopathic DM. On account of the
      increased morbidity and mortality of ILD-related DM, investigations for the early
      detection of ILD should be performed during initial evaluation and during follow
      up of patients with polymyositis/DM. Serum levels of anti-Jo-1 antibodies, chest
      roentgenogram, high-resolution computed tomography of the lungs, and pulmonary
      function tests, including diffusing capacity of the lung for carbon monoxide,
      should be routinely included. In those patients with evidence of DM-related ILD,
      a lung tissue biopsy should be considered for better prognostic stratification.
      Conversely, the presence of spontaneous pneumomediastinum, pneumothorax, and
      subcutaneous emphysema should prompt a search for underlying connective tissue
      diseases.

PMID- 23168663
TI  - A 36-year-old Man With Endobronchial Lesion and Bony Destruction of Ribs and
      Sacrum.
AB  - A 36-year-old male nonsmoker with fever, dyspnea, and cough of 2 weeks' duration
      presented to the emergency department. He reported left pleuritic chest pain and
      weight loss for the last 2 months. Chest radiology revealed a left lower lobe
      mass, a liver lesion, and bony destruction of right sacrum and ribs. Flexible
      bronchoscopy (FB) revealed an endobronchial (EB) tumorous lesion with cheesy
      material occluding the left lower lobe. Biopsies and cultures of the lung and rib
      lesions supported the diagnosis of tuberculosis (TB). Antituberculous therapy was
      started with rapid clinical improvement. A follow-up FB revealed partial
      resolution of the EB lesion. EBTB is a rare finding in the developed countries
      and the association with multiple skeletal and liver lesions is extremely rare.
      An EB lesion with skeletal lesions usually suggests malignancy or infectious
      diseases such as EB actinomycosis and fungal infections. The incidence of EBTB
      varies based on the population reported and has been described in children and
      young adults. Now, with an increase in international traveling and globalization,
      it is important for clinicians to include EBTB as a part of the differential
      diagnosis in patients presenting with EB lesions with or without associated
      systemic involvement. Early diagnosis and treatment could decrease the morbidity
      and potential development of bronchial stenosis associated with the disease. FB
      is highly recommended to identify those patients with poor prognosis who need
      close monitoring and bronchoscopic follow-up.

PMID- 23168664
TI  - Treatment of infection associated with tunneled pleural catheters.
AB  - Chronic indwelling tunneled pleural catheters are increasingly used for the
      treatment of malignant pleural effusions. Some common complications of these
      catheters include empyema and local site infection. Empyema is generally treated
      with the removal of the pleural catheter and the administration of systemic
      antibiotics. We propose a different and more conservative but effective method of
      the treatment of infected tunneled pleural catheters.

PMID- 23168665
TI  - Bronchial mucoepidermoid carcinoma: an unusual cause of complex cystic lung mass
      in a young man.
AB  - Bronchial mucopeidermoid carcinoma is extremely rare, with an incidence of 0.1 to
      0.2% of all primary lung tumors. It usually presents as an endobronchial mass
      with either partial or total occlusion of the airway lumen. Common clinical
      presentations are hemoptysis, airway obstruction, and recurrent atelectasis or
      pneumonia. We present a 27-year-old man who complained of chronic cough as a
      result of bronchial mucopeidermoid carcinoma with resultant obstructive lung
      changes.

PMID- 23168666
TI  - Endobronchial cryptococcosis:  a rare cause of lung collapse.
AB  - We encountered a 46-year-old immunocompetent male patient who presented with a
      right upper lobe collapse on a chest x-ray. A flexible bronchoscopic examination
      revealed an endobronchial mass emanating from the right upper lobe and
      obstructing the right mainstem bronchus. Bronchial washings and biopsy of the
      lesion were consistent with cryptococcal infection. The response to oral diflucan
      therapy was suboptimal. Subsequently, the patient underwent a successful
      bronchoscopic resection of this mass with the placement of an endobronchial
      stent. We report this rare case of endobronchial cryptococcal infection treated
      with a combination of an antifungal agent and bronchoscopic debulking.

PMID- 23168667
TI  - Tracheobronchopathia osteochondroplastica: an unusual presentation.
AB  - A 24-year-old woman presented with chronic cough and noisy breathing. Chest x-ray
      revealed diffuse irregularity and narrowing of the tracheal lumen. Thorax
      computed tomography showed irregularity, stenosis, and areas of ossification
      throughout the trachea and both main bronchia. Flexible bronchoscopy revealed
      multiple nodules protruding into the tracheal lumen. Histopathology of the
      nodules confirmed the diagnosis of "tracheobronchopathia osteochondroplastica."
      Tracheobronchopathia osteochondroplastica is a rare, benign disease that is
      characterized by multiple cartilaginous and osseous submucosal nodules protruding
      through tracheal lumen and large bronchia. The etiology is still unexplained.

PMID- 23168668
TI  - Ultrasound-guided Transthoracic Forceps Biopsy of a Peripheral Lung Mass.
AB  - Interventional pulmonologists are often called upon to diagnose a variety of
      intrathoracic abnormalities. Linear array endobronchial ultrasound has greatly
      increased the diagnostic accuracy of transbronchial needle aspiration for
      centrally located lesions in the chest, and radial endobronchial ultrasound and
      electromagnetic navigation have markedly increased the diagnostic yield for
      biopsies of peripheral pulmonary lesions. Image-guided transthoracic biopsies of
      peripheral pulmonary lesions that approximate the pleural surface have been
      successfully performed using the "core" biopsy devices, though these may be less
      successful for smaller pleural-based lesions given their design. In this case
      study, we describe a novel technique for the biopsy of a peripheral lung mass
      using ultrasound guidance and biopsy forceps.

PMID- 23168669
TI  - Closure of Gastro-pleuro-bronchial Fistula With Polymethyl Methacrolate and
      Endoclips: A Rare Complication of Gastric Bypass Surgery.
AB  - A unique noninvasive method was used to close a fistulous connection between the
      stomach and lung of a woman with recurrent bouts of pneumonia resulting from a
      rare complication of gastric bypass surgery.

PMID- 23168670
TI  - Stenting right main bronchus with montgomery T tube for upper lobe ventilation.
AB  - The involvement of the right main bronchus (RMB) along with the upper lobe
      bronchus and bronchus intermedius by malignant tumor is frequently encountered.
      However, the use of a stent for palliation of airway stenosis of the RMB might
      obstruct upper lobe orifice and pose complications such as atelectasis or
      recurrent pneumonia. We report the use of modified Montgomery T tube in a 78-year
      old man with neoplasm of the RMB by placing the tracheostomy arm of the T tube in
      the upper lobe bronchus to maintain its patency.

PMID- 23168671
TI  - An unusual case of persistent extrinsic bronchial compression.
AB  - Bronchomalacia is defined as diffuse or segmental bronchial weakness and easy
      compressibility. We present a rare case of a 67-year-old man with chronic cough
      as a consequence of focal bronchomalacia caused by persistent extrinsic
      compression of the left lower lobe bronchus by the descending aorta and the left
      lower lobe branch of the pulmonary artery. Focal bronchomalacia discovered during
      adulthood is most often acquired and can be attributed to extrinsic compression
      by abnormal blood vessels due to hypertension and lung transplantation or to
      bronchial disease processes. The natural history of bronchomalacia is typically
      progressive.

PMID- 23168672
TI  - An endobronchial lipoma: diagnosis remains a challenge.
AB  - Benign tumors of the endobronchial tree are rare, and among them endobronchial
      lipoma is the least common. It is histologically benign in character but may
      cause bronchial obstruction. We describe a case of a 68-year-old woman with an
      endobronchial lipoma arising in the left lower lobe bronchus who had been treated
      for frequent chest infections for the past 3 years.

PMID- 23168673
TI  - The story of the killian centenary award.

PMID- 23168674
TI  - Invitation to host the 19th world congress for bronchology in 2016.

PMID- 23168675
TI  - Supraspinal and spinal effects of L-trans-PDC, an inhibitor of glutamate
      transporter, on the micturition reflex in rats.
AB  - AIMS: Glutamate is a major excitatory transmitter in the central nervous system,
      controlling lower urinary tract function. Five types of glutamate transporters
      such as GLAST (EAAT1), GLT-1 (EAAT2), EAAC-1 (EAAT3), EAAT4, and EAAT5 have been
      cloned so far. In the current study we tested whether L-trans-pyrrolidine-2,4
      dicarboxylic acid (L-trans-PDC), a non-selective inhibitor of glutamate
      transporters that increases endogenous glutamate concentration, can affect the
      micturition reflex in urethane anesthetized rats. METHODS: Continuous
      cystometrograms (CMG, 0.04 ml/min infusion rate) were performed in two groups of
      urethane-anesthetized rats. A group of 18 rats was used for intrathecal
      administration of 1-10 ug of L-trans-PDC via an intrathecal catheter. In the
      second group of 18 rats, 1-10 ug of L-trans-PDC were administered
      intracerebroventricularly via a catheter inserted into the lateral ventricle.
      Micturition parameters were recorded and compared before and after drug
      administration. RESULTS: Intrathecal administration of L-trans-PDC at 1, 3, and
      10 ug (n = 6 per dose) increased intercontraction intervals in dose dependent
      fashion, but did not affect postvoid residual or basal pressure at any doses
      tested. Intracerebroventricular administration of L-trans-PDC at 1, 3, and 10 ug
      (n = 6 per dose) also increased intercontraction intervals in dose dependent
      fashion, but did not affect postvoid residual or basal pressure at any doses
      tested. CONCLUSIONS: The current results show that, in urethane-anesthetized
      rats, suppression of glutamate transporters by L-trans-PDC has an inhibitory
      effect on the micturition reflex at supraspinal and spinal sites, possibly via
      activation of glutamate-mediated inhibitory pathways.

PMID- 23168676
TI  - Transfer of normal S1 nerve root to reinnervate atonic bladder due to conus
      medullaris injury.
AB  - INTRODUCTION: Neurogenic bladder dysfunction after spinal cord injury (SCI) is a
      major medical and social problem. In this study we assessed the effectiveness of
      neurogenic bladder reinnervation in patients with SCI using a normal S1 nerve
      root. METHODS: Nine patients with bladder dysfunction caused by injury to the low
      conus medullaris (S2-S5) underwent a novel surgical procedure in which the
      unilateral proximal end of the S1 ventral root (VR) was anastomosed to the distal
      end of the S2 and S3 VRs. RESULTS: Seven patients regained satisfactory bladder
      control within 8-12 months after VR microanastomosis. The average residual urine
      volume decreased from 186.0 +/- 35.0 ml to 43.0 +/- 10.0 ml, and no urinary
      infections occurred. CONCLUSIONS: These results suggest the effectiveness of
      bladder innervation by S1 nerve transfer, which could provide a new approach for
      the reconstruction of atonic bladder function caused by low conus medullaris
      injuries.

PMID- 23168677
TI  - Synthesis of phenanthridinones via palladium-catalyzed C(sp2)-H
      aminocarbonylation of unprotected o-arylanilines.
AB  - An efficient synthesis of free (NH)-phenanthridinones through Pd-catalyzed
      C(sp(2))-H aminocarbonylation of unprotected o-arylanilines under an atmospheric
      pressure of CO has been developed. Some ortho heteroarene substituted anilines as
      well as N-alkyl protected o-arylanilines are also suitable substrates for this C
      H aminocarbonylation reaction.

PMID- 23168678
TI  - Investigation and comparison of the mechanistic steps in the [(Cp*MCl2)2] (Cp* =
      C5Me5; M = Rh, Ir)-catalyzed oxidative annulation of isoquinolones with alkynes.
AB  - The mechanism of the [(Cp*MCl(2))(2)] (M = Rh, Ir)-catalyzed oxidative annulation
      reaction of isoquinolones with alkynes was investigated in detail. In the first
      acetate-assisted C-H-activation process (cyclometalated step) and the subsequent
      mono-alkyne insertion into the M-C bonds of the cyclometalated compounds, both Rh
      and Ir complexes participated well. However, the desired final products,
      dibenzo[a,g]quinolizin-8-one derivatives, were only formed in high yield when the
      Rh species participated in the final oxidative coupling of the C-N bond.
      Moreover, a Rh(I) sandwich intermediate was isolated during this transformation.
      The iridium complexes were found to be inactive in the oxidative coupling
      processes. All of the relevant intermediates were fully characterized and
      determined by single-crystal X-ray diffraction analysis. Based on this
      mechanistic study, a Rh(III)->Rh(I)->Rh(III) catalytic cycle was proposed for
      this reaction.

PMID- 23168680
TI  - Body mass index and obstructive sleep apnoea.

PMID- 23168681
TI  - Stereoelectroencephalography:  surgical methodology, safety, and stereotactic
      application accuracy in 500 procedures.
AB  - BACKGROUND: Stereoelectroencephalography (SEEG) methodology, originally developed
      by Talairach and Bancaud, is progressively gaining popularity for the presurgical
      invasive evaluation of drug-resistant epilepsies. OBJECTIVE: To describe recent
      SEEG methodological implementations carried out in our center, to evaluate
      safety, and to analyze in vivo application accuracy in a consecutive series of
      500 procedures with a total of 6496 implanted electrodes. METHODS: Four hundred
      nineteen procedures were performed with the traditional 2-step surgical workflow,
      which was modified for the subsequent 81 procedures. The new workflow entailed
      acquisition of brain 3-dimensional angiography and magnetic resonance imaging in
      frameless and markerless conditions, advanced multimodal planning, and robot
      assisted implantation. Quantitative analysis for in vivo entry point and target
      point localization error was performed on a sub--data set of 118 procedures (1567
      electrodes). RESULTS: The methodology allowed successful implantation in all
      cases. Major complication rate was 12 of 500 (2.4%), including 1 death for
      indirect morbidity. Median entry point localization error was 1.43 mm
      (interquartile range, 0.91-2.21 mm) with the traditional workflow and 0.78 mm
      (interquartile range, 0.49-1.08 mm) with the new one (P < 2.2 * 10). Median
      target point localization errors were 2.69 mm (interquartile range, 1.89-3.67 mm)
      and 1.77 mm (interquartile range, 1.25-2.51 mm; P < 2.2 * 10), respectively.
      CONCLUSION: SEEG is a safe and accurate procedure for the invasive assessment of
      the epileptogenic zone. Traditional Talairach methodology, implemented by
      multimodal planning and robot-assisted surgery, allows direct electrical
      recording from superficial and deep-seated brain structures, providing essential
      information in the most complex cases of drug-resistant epilepsy.

PMID- 23168682
TI  - Drug-induced sleep endoscopy for upper airway evaluation in children with
      obstructive sleep apnea.
AB  - OBJECTIVES/HYPOTHESIS: To evaluate sites and characteristics of upper airway
      obstruction, as detected with drug-induced sleep endoscopy (DISE) in children
      with obstructive sleep apnea (OSA). MATERIAL AND METHODS: The medical records of
      children who underwent DISE were reviewed. Data pertaining to demographics, past
      medical history, body mass index, tonsil size, adenoid size, polysomnography, and
      DISE were obtained. RESULTS: Eighty-two children had DISE and severity of OSA was
      mild in four patients, moderate in 17, and severe in 61. DISE revealed
      obstruction at the level of velum in 67 patients, oropharynx/lateral walls in 72
      patients, tongue in 10 patients, and epiglottis in 10 patients.
      Oropharynx/lateral walls were the most common single site of obstruction. The
      majority of children had obstruction at multiple sites. Combination of velum and
      oropharynx/lateral walls was the most common multiple sites of obstruction.
      Prevalence of complete obstruction at velum and oropharynx/lateral walls in
      children with severe or moderate OSA were greater than those of children with
      mild OSA. Complete obstruction at oropharynx/lateral walls was documented in 50%
      of children with grade I tonsils and 64% of children with grade II tonsils.
      CONCLUSION: The oropharynx/lateral walls are the most common site of obstruction
      in children with single site obstruction. Combined oropharynx/lateral walls and
      velum obstruction was the most common sites of obstruction in children with
      multiple site obstruction. Children with grade I and grade II tonsils may suffer
      from complete airway obstruction. DISE is a useful tool to identify upper airway
      obstruction sites in addition to adenotonsillar hypertrophy.

PMID- 23168684
TI  - A short and flexible route to tetrahydropyran-4-ones via conjugated nitrile
      oxides cycloaddition and oxa-Michael cyclization: a concise diastereoselective
      total synthesis of (+/-)-diospongin A.
AB  - A short and flexible [3+2+1] synthetic strategy was developed for the synthesis
      of substituted tetrahydropyran-4-ones, featuring [3+2]-cycloaddition of
      alpha,beta-unsaturated nitrile oxides and alkenes and oxa-Michael cyclization in
      a 6-endo-trig fashion. The efficiency of this synthetic strategy was further
      demonstrated by the concise total synthesis of (+/-)-diospongin A in 8 steps with
      20.2% yield.

PMID- 23168683
TI  - Urocortin increased LPS-induced endothelial permeability by regulating the
      cadherin-catenin complex via corticotrophin-releasing hormone receptor 2.
AB  - Urocortin (Ucn1), a member of corticotrophin-releasing hormone (CRH) family, has
      been reported to be upregulated in inflammatory diseases and function as an
      autocrine or paracrine inflammatory mediator. Growing evidence shows that Ucn1
      increases the endothelial permeability in inflammatory conditions; however, the
      detailed mechanisms are not clear. In the present study, we investigated the
      mechanisms of increased endothelial permeability by Ucn1 in human umbilical vein
      endothelial cells (HUVECs) exposed to lipopolysaccharide (LPS). Pretreatment of
      HUVECs with Ucn1 increased the endothelial cell permeability, which was augmented
      by LPS synergistically. Significant downregulation of VE-cadherin expression was
      also observed. Moreover, Ucn1 increased phosphorylation of protein kinase D (PKD)
      and heat shock protein 27 (HSP27) in a time- and CRHR(2) -dependent manner.
      Inhibition of PKD and HSP27 drastically attenuated Ucn1-induced downregulation of
      VE-cadherin expression. Further investigations demonstrated that Ucn1
      phosphorylated beta-catenin at Ser552 to disrupt the cadherin-catenin complex and
      hence promote the disassociation of beta-catenin and VE-cadherin. Disassociation
      of beta-catenin and VE-cadherin resulted in decreased VE-cadherin expression
      while on the contrary beta-catenin was increased, which may due to the
      inactivation of GSK-3beta. Increased beta-catenin translocated into the nucleus
      and subsequently bound to TCF/LEF site, contributing to the elevated expression
      of vascular endothelial growth factor (VEGF). The above effects of Ucn1 were
      completely reversed by CRHR(2) receptor blocker, antisauvagine-30. Taken
      together, our data suggest that Ucn1 increase LPS-induced endothelial
      permeability by disrupting the VE-cadherin-beta-catenin complex via activation of
      CRHR(2) and PKD-HSP27 signaling pathway.

PMID- 23168685
TI  - Characteristics of biofilm attaching to carriers in moving bed biofilm reactor
      used to treat vitamin C wastewater.
AB  - In order to investigate characteristics of biofilm attaching firmly to carriers
      in the moving bed biofilm reactor (MBBR) used for vitamin C wastewater treatment,
      experiments were undertaken with instrumental analysis methods. Scanning electron
      microscopy (SEM) micrographs of MBBR biofilms revealed that there were rod-shaped
      microbes and cocci in the biofilm, and microbes were embedded within medium
      substances and the biofilm matrix adhered firmly to carriers, leading to the
      formation of a smooth compacted surface at the base of the biofilm. Transmission
      electron microscopy (TEM) analysis revealed that extracellular polymeric
      substances (EPS) layer surrounded cell, sequestered inorganics to form a mixed
      structure, which ensured firm attachment of the biofilm to the carrier. X-ray
      diffraction (XRD) experiments and thermogravimetry analysis revealed that (i) the
      biofilm contained many inorganic substances, about 70.5%, and the inorganic
      substances contained multiple classes of inorganic with a high boiling point;
      (ii) inorganic elements such as calcium and phosphorous were selectively absorbed
      and accumulated in the biofilm as insoluble compounds with amorphous phases,
      rendering the biofilm highly resistant to detachment. Fourier-transform infrared
      (FTIR) spectroscopy showed carbohydrates were the main EPS.

PMID- 23168686
TI  - Identification of protein complexes in Escherichia coli using sequential peptide
      affinity purification in combination with tandem mass spectrometry.
AB  - Since most cellular processes are mediated by macromolecular assemblies, the
      systematic identification of protein-protein interactions (PPI) and the
      identification of the subunit composition of multi-protein complexes can provide
      insight into gene function and enhance understanding of biological systems(1, 2).
      Physical interactions can be mapped with high confidence vialarge-scale isolation
      and characterization of endogenous protein complexes under near-physiological
      conditions based on affinity purification of chromosomally-tagged proteins in
      combination with mass spectrometry (APMS). This approach has been successfully
      applied in evolutionarily diverse organisms, including yeast, flies, worms,
      mammalian cells, and bacteria(1-6). In particular, we have generated a carboxy
      terminal Sequential Peptide Affinity (SPA) dual tagging system for affinity
      purifying native protein complexes from cultured gram-negative Escherichia coli,
      using genetically-tractable host laboratory strains that are well-suited for
      genome-wide investigations of the fundamental biology and conserved processes of
      prokaryotes(1, 2, 7). Our SPA-tagging system is analogous to the tandem affinity
      purification method developed originally for yeast(8, 9), and consists of a
      calmodulin binding peptide (CBP) followed by the cleavage site for the highly
      specific tobacco etch virus (TEV) protease and three copies of the FLAG epitope
      (3X FLAG), allowing for two consecutive rounds of affinity enrichment. After
      cassette amplification, sequence-specific linear PCR products encoding the SPA
      tag and a selectable marker are integrated and expressed in frame as carboxy
      terminal fusions in a DY330 background that is induced to transiently express a
      highly efficient heterologous bacteriophage lambda recombination system(10).
      Subsequent dual-step purification using calmodulin and anti-FLAG affinity beads
      enables the highly selective and efficient recovery of even low abundance protein
      complexes from large-scale cultures. Tandem mass spectrometry is then used to
      identify the stably co-purifying proteins with high sensitivity (low nanogram
      detection limits). Here, we describe detailed step-by-step procedures we commonly
      use for systematic protein tagging, purification and mass spectrometry-based
      analysis of soluble protein complexes from E. coli, which can be scaled up and
      potentially tailored to other bacterial species, including certain opportunistic
      pathogens that are amenable to recombineering. The resulting physical
      interactions can often reveal interesting unexpected components and connections
      suggesting novel mechanistic links. Integration of the PPI data with alternate
      molecular association data such as genetic (gene-gene) interactions and genomic
      context (GC) predictions can facilitate elucidation of the global molecular
      organization of multi-protein complexes within biological pathways. The networks
      generated for E. coli can be used to gain insight into the functional
      architecture of orthologous gene products in other microbes for which functional
      annotations are currently lacking.

PMID- 23168687
TI  - A rare case of split hand/foot malformation with sensorineural hearing loss and
      Mondini dysplasia.

PMID- 23168688
TI  - Structure and stability of borohydride on Au(111) and Au3M(111) (M = Cr, Mn, Fe,
      Co, Ni) surfaces.
AB  - We study the adsorption of borohydride on Au and Au-based alloys (Au(3)M with M =
      Cr, Mn, Fe, Co, and Ni) using first-principles calculations based on spin
      polarized density functional theory. Favorable molecular adsorption and greater
      adsorption stability compared to pure Au are achieved on Au(3)M alloys. For these
      alloys, there is an emergence of unoccupied states in the surface d band around
      the Fermi level with respect to the fully occupied d band of pure Au. Thus, the
      derived antibonding state of the sp-d interaction is upshifted and becomes
      unoccupied compared to pure Au. The B-H bond elongation of the adsorbed
      borohydride on these alloy surfaces points to the role of surface-parallel (d(xy)
      and d(x(2)-y(2)) states) components of the d-band of the alloying metal M, most
      pronouncedly in the cases of M = Co or Ni. On the alloy surfaces, B binds
      directly with the alloying metal, unlike in the case of pure Au where the surface
      bonding is through the H atoms. These results pose relevant insights into the
      design of Au-based anode catalysts for the direct borohydride fuel cell.

PMID- 23168689
TI  - Nipple-sparing mastectomy in modern breast practice.
AB  - Breast cancer management has evolved from the conventional radical Halsted to a
      fully integrated multidisciplinary approach. Nipple sparing mastectomy (NSM) is
      an innovative technique that preserves native breast envelope without mutilation
      of nipple-areola complex (NAC), thus providing a reasonable alternative for early
      cancers without NAC involvement and prophylactic high risk patients and avoids
      multiple surgical procedures required for reconstruction. This article aims to
      critically review indications, intra-operative protocols, radiotherapy planning
      and limitations of NSM. Patient selection should be based on study of breast duct
      anatomy by Magnetic Resonance Imaging, mammographic tumor-nipple distance and
      obligatory intra-operative frozen section from retro-areolar tissue. Tumor size,
      axillary lymph node status, lymphovascular invasion and/or degree of intraductal
      component are factors used to include NSM candidates based on institutional
      practice. Given the heterogeneity of patients and lack of standardization of
      preoperative investigations, surgical technique and pathologic sampling of retro
      areola tissue so far, mandates a multi-institutional prospective study to define
      and validate a role for NSM in invasive breast cancer and DCIS. Nipple necrosis
      is an important NSM complication which can be greatly reduced using alternative
      skin incisions. Even if the nipple survives, an insensate nipple and lack of
      sexual function is common and requires preoperative counseling and discussion.
      Finally the relation and timing of intra-operative versus adjuvant breast
      radiation and tailoring of dosage and delivery methods has not been fully
      explored. Although NSM reduces psychological trauma associated with nipple loss,
      the oncologic safety as well as functional and aesthetic outcomes needs
      additional investigation.

PMID- 23168690
TI  - Simplifying the author and reader experience.

PMID- 23168691
TI  - Depression: a major public health problem in need of a multi-sectoral response.

PMID- 23168692
TI  - Three decades of ICSSR-ICMR Committee Report & the re-assertion of social
      determinants of health.

PMID- 23168693
TI  - Financial risk protection & chronic disease care.

PMID- 23168694
TI  - Association of cardiovascular risks with sympathovagal imbalance in rheumatoid
      arthritis.

PMID- 23168695
TI  - Helicobacter pylori infection in India from a western perspective.
AB  - Helicobacter pylori is a common bacterial infectious disease whose manifestations
      predominately affect the gastrointestinal tract. India is the prototypical
      developing country as far as H. pylori infection is concerned and more than 20
      million Indians are estimated to suffer from peptic ulcer disease. Considering
      the high level of medical research and of the pharmaceutical industry, one would
      expect that India would be the source of much needed information regarding new
      therapies and approaches that remain effective in the presence of antimicrobial
      resistance, new methods to reliably prevent reinfection, and the development of
      therapeutic and preventive vaccines. Here we discuss H. pylori as a problem in
      India with an emphasis on H. pylori infection as a serious transmissible
      infectious disease. We discuss the pros and cons of eradication of H. pylori from
      the entire population and come down on the side of eradication. The available
      data from India regarding antimicrobial use and resistance as well as the
      effectiveness of various treatments are discussed. Rigorous ongoing studies to
      provide current regional antibiotic resistance patterns coupled with data
      concerning the success rate with different treatment regimens are needed to guide
      therapy. A systematic approach to identify reliably effective (e.g., 90% or
      greater treatment success) cost-effective regimens is suggested as well as
      details of regimens likely to be effective in India. H. pylori is just one of the
      health care problems faced in India, but one where all the resources are on hand
      to understand and solve it.

PMID- 23168696
TI  - Men who have sex with men in India: a diverse population in need of medical
      attention.
AB  - A significant proportion of men engage in sexual relationships with other men
      which has direct health implications, but the unique health care needs of these
      patients are often ignored or overlooked. Moreover, due to a fear of
      stigmatization by the medical community, one of the more significant health risks
      for men who have sex with men (MSM) may be that they avoid routine or appropriate
      health care. Physicians and other providers can help overcome this barrier and
      improve the health care of MSM by keeping a non-judgmental attitude toward these
      patients, differentiating sexual behaviour from sexual identity, communicating
      with gender neutral terms, and maintaining awareness of how their own attitudes
      affect clinical judgment. The purpose of this article is to help contextualize
      health issues affecting MSM and provide a framework for physicians and other
      providers to deliver optimum and appropriate health care for men who have sex
      with men in India.

PMID- 23168698
TI  - Catastrophic health expenditure & coping strategies associated with acute
      coronary syndrome in Kerala, India.
AB  - BACKGROUND & OBJECTIVES: India contributes a significant number of deaths
      attributed to coronary artery disease (CAD) compared to the rest of the world.
      Data on catastrophic health expenditure (CHE) related to acute coronary syndrome
      (ACS), the major cause of deaths in CAD, are limited in the literature. We
      estimated the magnitude of CHE and studied the strategies used to cope with CHE.
      METHODS: Two hundred and ten ACS patients (mean age 56 yr, 83% men) were randomly
      selected proportionately from six hospitals in Thiruvananthapuram district,
      Kerala, India. Information on demographics, ACS-related out-of-pocket expenditure
      and coping strategies was collected using a pre-tested structured interview
      schedule. CHE, defined as ACS-related expenditures exceeding 40 per cent of a
      household's capacity to pay, was estimated using the World Health Organization
      methods. Health security was defined as protection against out-of-pocket
      expenditure through an employer or government provided social security scheme.
      Socio-demographic variables, effect on participants' employment, loans or asset
      sales for treatment purposes, health security coverage and type of treatment were
      considered as potential correlates of CHE. Multiple logistic regression analyses
      were conducted to identify the correlates of CHE. RESULTS: CHE was experienced by
      84 per cent (95% CI: 79.04, 88.96) of participants as a consequence of treating
      ACS. Participants belonging to low socio-economic status (SES) were 15 times
      (odds ratio (OR): 14.51, 95% CI: 1.69-124.41), whose jobs were adversely affected
      were seven times (OR: 7.21, CI: 1.54-33.80), who had no health security were six
      times (OR: 6.00, CI: 2.02-17.81) and who underwent any intervention were three
      times (OR: 3.24, CI: 1.03-10.16) more likely to have CHE compared to their
      counterparts. The coping strategies adopted by the participants were loans (41%),
      savings (14%), health insurance (8%) and a combination of the above (37%).
      INTERPRETATION & CONCLUSIONS: Our findings show that viable financing mechanism
      for treating ACS is warranted to prevent CHE particularly among low SES
      participants, those having no health security, requiring intervention procedures
      and those with adversely affected employment.

PMID- 23168697
TI  - Oncolytic viruses & their specific targeting to tumour cells.
AB  - Cancer is one of the major causes of death worldwide. In spite of achieving
      significant successes in medical sciences in the past few decades, the number of
      deaths due to cancer remains unchecked. The conventional chemotherapy and
      radiotherapy have limited therapeutic index and a plethora of treatment related
      side effects. This situation has provided an impetus for search of novel
      therapeutic strategies that can selectively destroy the tumour cells, leaving the
      normal cells unharmed. Viral oncotherapy is such a promising treatment modality
      that offers unique opportunity for tumour targeting. Numerous viruses with
      inherent anti-cancer activity have been identified and are in different phases of
      clinical trials. In the era of modern biotechnology and with better understanding
      of cancer biology and virology, it has become feasible to engineer the oncolytic
      viruses (OVs) to increase their tumour selectivity and enhance their oncolytic
      activity. In this review, the mechanisms by which oncolytic viruses kill the
      tumour cells have been discussed as also the development made in virotherapy for
      cancer treatment with emphasis on their tumour specific targeting.

PMID- 23168699
TI  - A pilot study on short term heart rate variability & its correlation with disease
      activity in Indian patients with rheumatoid arthritis.
AB  - BACKGROUND & OBJECTIVES: Cardiovascular complications may lead to mortality in
      patients with rheumatoid arthritis (RA). We assessed heart rate variability
      (HRV), an important autonomic function, to quantify the risk for cardiovascular
      complications in Indian patients with RA. METHODS: The study was carried out in
      RA patients (n=45) diagnosed as per American College of Rheumatology criteria and
      healthy controls. HRV recording and analysis was done using Nevrokard software
      using time and frequency domain analyses. The overall autonomic tone,
      parasympathetic drive, sympathetic drive and sympatho-vagal ratio were quantified
      by using various parameters. It included standard deviation of all R-R intervals
      (SDNN), standard deviation of successive differences between adjoining normal
      cycles (SDSD), root-mean square of successive differences (RMSSD), and number of
      R-R intervals differing by >50 ms from adjacent intervals (NN50) in the time
      domain analysis. In frequency domain analysis, low frequency (LF) and high
      frequency (HF), LF/HF and total power were assessed. RESULTS: Demographic profile
      was comparable between groups; however, systolic BP was higher in patients with
      RA. SDNN, SDSD, RMSSD, NN50, LF and HF power and total power (ms x ms) were
      significantly lower in patients with RA versus healthy controls (P<0.001).
      Disease activity score at 28 joints indicating severity of the disease was
      significantly and positively correlated with SDSD (r=0.375, R 2 =14.06; P=0.045)
      while LF and HF power (ms * ms) were significantly and inversely correlated with
      rheumatoid factor (r=-0.438 and -0.445; R 2 =19.1 and 19.8; P=0.017 and 0.016,
      respectively). INTERPRETATION & CONCLUSIONS: HRV was significantly altered in
      patients with RA and independently associated with disease activity. Hence
      autonomic function testing, using HRV, may be useful as part of cardiovascular
      risk assessment in these patients.

PMID- 23168700
TI  - Extensively drug-resistant tuberculosis in India: a review.
AB  - BACKGROUND & OBJECTIVES: Extensively drug resistant tuberculosis (XDR-TB) has
      become a new threat for the control of TB in many countries including India. Its
      prevalence is not known in India as there is no nation-wide surveillance.
      However, there have been some reports from various hospitals in the country.
      METHODS: We have reviewed the studies/information available in the public domain
      and found data from 10 tertiary care centres in 9 cities in India. RESULTS: A
      total of 598 isolates of XDR Mycobacterium tuberculosis have been reported in the
      studies included. However, the reliability of microbiological methods used in
      these studies was not checked and thus the XDR-TB data remained invalidated in
      reference laboratories. INTERPRETATION & CONCLUSIONS: Systematic surveillance and
      containment interventions are urgently needed.

PMID- 23168701
TI  - Association between polymorphisms at N-acetyltransferase 1 (NAT1) & risk of oral
      leukoplakia & cancer.
AB  - BACKGROUND & OBJECTIVES: N-acetyltransferases 1 and 2 (NAT1 and NAT2) are
      important enzymes for metabolism of tobacco carcinogens. Due to polymorphisms,
      improper activities of these enzymes might lead to the formation of DNA adducts
      that may modulate risk of tobacco related oral precancer and cancer. Previously,
      it was shown that NAT2 polymorphisms did not modulate the risk of oral precancer
      and cancer. We undertook this study to check whether polymorphisms at NAT1 can
      modulate the risk of oral leukoplakia and cancer either alone or in combination
      with NAT2. METHODS: Genotypes at four SNPs on NAT1 were determined by TaqMan
      method in 389 controls, 224 leukoplakia and 310 cancer patients. Genotype data
      were analyzed to know haplotypes and acetylation status of individuals and, then
      to estimate the risk of diseases. Using our previously published NAT2 data,
      combination of NAT1 and NAT2 acetylation genotypes of patients and controls were
      also analyzed to estimate the risk of diseases. RESULTS: Analysis of NAT1
      genotype data revealed that 1088T and 1095C alleles exist in strong linkage
      disequilibrium (r 2 =0.97, P<0.0001) and SNPs are in Hardy-Weinberg Equilibrium
      (P=0.1). Wild type or normal acetylating and variant or rapid acetylating alleles
      were two major alleles (frequencies 0.62 and 0.36, respectively) present in the
      control population. NAT1 rapid acetylation could not modulate the risk of
      leukoplakia and cancer (OR=0.9, 95% CI: 0.6-1.3; OR=1.0, 95% CI: 0.7-1.4,
      respectively). Analysis of combined NAT1 and NAT2 acetylating data also showed no
      significant enhancement of the risk of diseases. INTERPRETATION & CONCLUSIONS:
      NAT1 rapid acetylation alone as well as combination of NAT1 rapid-NAT2 slow
      acetylation did not modulate the risk of oral precancer and cancer in our patient
      population. So, NAT1/NAT2 metabolized carcinogen products may not be involved in
      tobacco related oral precancer and cancer. It may be interpreted that large
      sample size as well as combination of polymorphisms at other candidate loci may
      be important to estimate the risk of a complex disease like oral cancer.

PMID- 23168702
TI  - Factors affecting 30-month survival in lung cancer patients.
AB  - BACKGROUND & OBJECTIVES: Age adjusted incidence rate of lung cancer in India
      ranges from 7.4 to 13.1 per 100,000 among males and 3.9 to 5.8 per 100,000 among
      females. The factors affecting survival in lung cancer patients in India are not
      fully understood. The current study was undertaken to evaluate the factors
      affecting survival in patients diagnosed with lung cancer attending a tertiary
      care cancer institute in Bangalore, Karnataka, India. METHODS: Consecutive
      patients with primary lung cancer attending Bangalore Institute of Oncology, a
      tertiary care centre at Bangalore, between 2006 and 2009 were included.
      Demographic, clinical, radiological data were collected retrospectively from the
      medical records. RESULTS: A total of 170 consecutive subjects (128 males, 42
      females) diagnosed to have lung cancer; 151 non-small cell lung cancer (NSCLC)
      and 19 small cell lung cancer (SCLC) were included. A higher proportion of never
      smokers (54.1%) were observed, mostly presenting below the age of 60 yr. Most
      subjects were in stage IV and III at the time of diagnosis. More than 50 per cent
      of patients presented with late stage lung cancer even though the duration of
      symptoms is less than 2 months. The 30-month overall survival rates for smokers
      and never-smokers were 32 and 49 per cent, respectively. No significant
      differences were observed in 30 month survival based on age at presentation,
      gender and type of lung cancer. Cox proportional hazards model identified never
      smokers and duration of symptoms less than 1 month as factors adversely affecting
      survival. INTERPRETATION & CONCLUSIONS: Our results showed that lung cancer in
      Indians involved younger subjects and associated with poorer survival as compared
      to other ethnic population. Studies on large sample need to be done to evaluate
      risk factors in lung cancer patients.

PMID- 23168703
TI  - Implication of DNA repair genes in prostate tumourigenesis in Indian males.
AB  - BACKGROUND & OBJECTIVES: Prostate cancer (CaP) is the fifth most common cancer
      among Indian men. Tumour protein p53 (TP53) gene increases the fidelity of DNA
      replication and homologous recombination by transcriptional transactivation of
      mismatch repair (MMR) genes. DNA repair thus has a potential role in molecular
      carcinogenesis of CaP. The aim of the present study was to identify mutations,
      and polymorphisms in TP53 gene and MMR protein expression in CaP in Indian male
      population. METHODS: TP53 codon 72 polymorphism was analysed in 105 CaP, 120
      benign prostatic hyperplasia (BPH) cases and 106 normal controls. Mutational
      analysis of TP53 was done in DNA extracted from formalin fixed paraffin embedded
      tissue of 80 CaP and 24 BPH cases. Expression of MMR proteins viz. hMLH1, hMSH2,
      hPMS1 and hPMS2 was studied in 80 CaP, 15 prostatic intraepithelial neoplasia
      (PIN) and 15 BPH cases. RESULTS: A somatic C/A variation at the intronic boundary
      of exon 7 in TP53 gene was observed in one each biopsy samples from CaP and BPH.
      A significant association of codon 72 TP53 Pro/Pro genotype was observed with the
      risk of CaP (OR, 2.59, P=0.02) and BPH (OR, 6.27, P<0.001). Immunohistochemical
      analysis of MMR proteins showed maximum loss of hPMS1 expression in cases of CaP
      and PIN while no loss in expression of MMR proteins was observed in BPH cases.
      The study also identified a significant loss of hPMS2 protein in poorly
      differentiated tumours (Gleason score >7) than in well differentiated tumours
      (Gleason score 3-6) (P<0.05). INTERPRETATION & CONCLUSIONS: The results of the
      present study demonstrate that TP53 codon 72 polymorphism plays significant role
      in the pathogenesis and susceptibility to CaP and BPH. Also, an aberrant MMR
      protein expression could be involved in progression of prostate cancer through
      PIN, early CaP to aggressive CaP. The loss of hPMS2 protein expression may serve
      as a marker for progression of CaP.

PMID- 23168704
TI  - An amperometric cholesterol biosensor based on epoxy resin membrane bound
      cholesterol oxidase.
AB  - BACKGROUND & OBJECTIVES: The use of epoxy resin membrane as a support for
      immobilization of enzyme has resulted into improved sensitivity and stability of
      biosensors for uric acid, ascorbic acid and polyphenols. The present work was
      aimed to prepare an improved amperometric biosensor for determination of serum
      cholesterol required in the diagnostics and management of certain pathological
      conditions. METHODS: Epoxy resin membrane with immobilized cholesterol oxidase
      was mounted on the cleaned platinum (Pt) electrode with a parafilm to construct a
      working electrode. This working electrode along with Ag/AgCl as reference and Ag
      wire as an auxiliary electrode were connected through a three terminal
      electrometer to construct a cholesterol biosensor. RESULTS: The sensor showed
      optimum response within 25 sec at pH 7.0 and 45 degrees C. The linear working
      range of biosensor was 1.0 to 8.0 mM cholesterol. K m and I max for cholesterol
      were 5.0 mM and 9.09 MUA, respectively. The biosensor measured serum cholesterol.
      The minimum detection limit of the sensor was 1.0 mM. The mean analytical
      recoveries of added cholesterol in serum (2.84 and 4.13 mM) were 91.4 +/- 2.8 and
      92.3 +/- 3.1 per cent (n=6), respectively. Within and between assay coefficient
      of variation (CV) were <2 and <4 per cent, respectively. Biosensor had a storage
      life of 6 months at 4 o C. INTERPRETATION & CONCLUSIONS: The use of epoxy resin
      membrane as a support for immobilization of cholesterol oxidase has resulted into
      an improved amperometric cholesterol biosensor. The present biosensor had an
      advantage over the existing biosensors as it worked at comparatively lower
      potential.

PMID- 23168705
TI  - Resolution of immune response by recombinant transforming growth factor-beta
      (rTGF-beta) during influenza A virus infection.
AB  - BACKGROUND & OBJECTIVES: Replication of influenza A virus in the respiratory
      tract leads to cell damage and liberation of cytokines and chemokines. The in
      vivo cytokine induction and modulation by recombinant transforming growth factor-
      beta1 (rTGF-beta1) has not been studied. Therefore, in the present study the
      effect of rTGF-beta1, a potent immunomodulatory cytokine which has anti
      inflammatory properties and downregulates the release of inflammatory molecules,
      against influenza-virus infection in the airway of mice was investigated.
      METHODS: rTGF-beta1 was administered intravenously to mice with concomitant
      intranasal infection of influenza A/Udorn/317/72 (H3N2) virus, and the survival
      rate, virus titre, histopathological changes and levels of factors regulating
      inflammation in the airway fluid were analysed. RESULT: The immune response to
      influenza A virus was characterized by an influx of both macrophages and
      lymphocytes into the lungs of the infected host. rTGF-beta1 significantly
      suppressed virus multiplication and improved the survival rate of mice. rTGF
      beta1 downregulated infiltration of neutrophils and the release of inflammatory
      molecules, such as interferon-gamma (IFN-gamma), interleukin-1 beta (IL-1beta)
      and stimulated release of IL-10 that potentiates anti-inflammatory response into
      airway. INTERPRETATION & CONCLUSIONS: A generalized pulmonary inflammation does
      not contribute to viral clearance but represents an immunological background
      within which antiviral immunity operates. Treatment with rTGF-beta1 reduced
      macrophage count and neutrophils influx in lungs of infected mice.

PMID- 23168706
TI  - Outbreak of dengue virus serotype-2 (DENV-2) of Cambodian origin in Manipur,
      India - association with meteorological factors.
AB  - BACKGROUND & OBJECTIVES: Dengue is a major health problem in many parts of India
      and its neighbouring countries. Dengue cases have not been reported from Manipur,
      a northeastern State of India till 2007. But, the sudden outbreak of fever with
      febrile illness during 2007 and 2008, suspected to be dengue/dengue haemorrhagic
      fever was investigated to detect the causative agent. Potential impact of
      climatic variables on dengue transmission has been documented and hence the
      association between climatic factors, entomological parameters and dengue cases
      was also analysed. METHODS: Forty two and 16 blood samples were collected from
      patients suspected to have dengue infection in the year 2007 and 2008,
      respectively. Viral RNA was extracted from serum samples and subjected to
      multiplex one step RT-PCR assay. Dengue specific amplicons were sequenced and
      phylogenetic analysis was carried out. Multiyear trend analysis and 't' test were
      performed for the comparison of different meteorological variables between the
      years 2000-2004 and 2005-2008. RESULTS: The aetiological agent was found to be
      DENV-2 and the phylogenetic analysis showed that the isolate was similar to that
      of Cambodian isolate. There was a significant difference in minimum temperature
      (P<0.05), Relative humidity - morning hours (P<0.001), relative humanity -
      afternoon hours (P<0.01) and cumulative precipitation (P< 0.05) between the years
      2000-2004 and 2005-2008. INTERPRETATION & CONCLUSIONS: The sudden outbreak of
      dengue fever in Manipur State occurred was possibly due to the increased
      temperature, relative humidity and decrease in cumulative precipitation. These
      climatic factors would have contributed to the Aedes mosquito abundance and
      increased virus transmission. Proper diseases surveillance system integrated with
      meteorological warning system and management of vector breeding sites will
      prevent such outbreaks in future.

PMID- 23168707
TI  - Molecular epidemiology of Vibrio cholerae causing outbreaks & sporadic cholera in
      northern India.
AB  - BACKGROUND & OBJECTIVES: Several outbreaks of cholera have been reported in
      Chandigarh region during a span of seven years from 2002-2008. The genetic
      characteristics of Vibrio cholerae isolates obtained during these outbreaks have
      not been adequately studied. The aim of this study was to do molecular typing of
      V. cholerae isolated from the sporadic and outbreak cases by pulsed-field gel
      electrophoresis (PFGE), Rep-PCR and ribotyping. METHODS: Fifty representative
      isolates of V. cholerae from outbreak as well as sporadic cases were subjected to
      molecular typing by PFGE, 173 isolates (163 clinical and 10 environmental) were
      typed by rep-PCR and ribotyping. Ribotyping was done by determination of rRNA
      restriction pattern of BglI restriction digestion and hybridization with 7.2 kb
      rRNA probe of pKK3535 plasmid using DIG DNA labelling and detection kit.
      Universal VC1 primer was used for rep-PCR. RESULTS: PFGE generated 15 pulsotypes,
      of which four matched the published pulsotypes and there were 11 new pulsotypes.
      PFGE was the most discriminatory method that could differentiate between isolates
      belonging to single ribotype. Pulsotype P1 corresponding to known pulsotype H1
      was the major pulsotype till 2003. Pulsotype P3 corresponding to known pulsotype
      L emerged in 2004. The 2007 outbreaks in Punjab and Haryana were caused by P5
      though P1 and P3 were isolated from the sporadic cases from the same region. The
      2008 outbreak was caused by pulsotypes P6 and P7. Ribotype IV was the most
      predominant followed by RIII. This ribotype was not isolated after 2003 and
      ribotype IV became the most predominant 2004 onwards. Of the two unknown
      ribotypes (UNI and UN2), UNI was more common (27 isolates). Rep-PCR was the least
      discriminatory and divided all clinical isolates into four major profiles. The
      dendrogram analysis of PFGE revealed similarity of some clinical isolates with
      environmental isolates indicating the genetic relatedness. INTERPRETATION &
      CONCLUSION: Our findings showed that Rep-PCR was least discriminatory method.
      Ribotyping was a reliable and reproducible method. Ribotype IV was predominant
      ribotype followed by RIII. A total of 15 pulsotypes were generated and 11 of
      these were not reported earlier. Genetic relatedness was shown by clinical and
      environmental isolates which needs to be confirmed in future studies.

PMID- 23168708
TI  - Analysis of p53, K-ras gene mutation & Helicobacter pylori infection in patients
      with gastric cancer & peptic ulcer disease at a tertiary care hospital in north
      India.
AB  - BACKGROUND & OBJECTIVES: Mutations in the oncogene and tumour suppressor genes
      play an important role in carcinogenesis. We investigated the association of p53
      and K-ras gene mutation and Helicobacter pylori infection in patients with
      gastric cancer (GC) and peptic ulcer disease (PUD) attending a tertiary care
      hospital in north India. METHODS: In total, 348 adult patients [62 GC, 45 PUD and
      241 non-ulcer dyspepsia (NUD)] who underwent an upper gastrointestinal endoscopy
      were enrolled. H. pylori infection was diagnosed by rapid urease test, culture,
      histopathology and PCR. Mutation in the exon 5-8 of p53 gene was analyzed by PCR
      single stranded conformational polymorphism (SSCP) and confirmed by sequence
      analysis. K-ras gene codon 12 mutation was analyzed by PCR-based restriction
      fragment length polymorphism. RESULTS: Overall p53 gene mutation was found in 4.6
      per cent of the study population, and its distribution in GC, PUD and NUD was 21,
      4.4 and 0.4 per cent, respectively. p53 gene mutation was significantly higher in
      patients with GC than PUD (P<0.05) and NUD (P<0.001). No difference in p53 gene
      mutation was observed between H. pylori infected and non-infected individuals. K
      ras gene mutation was absent in all the patients. INTERPRETATION & CONCLUSIONS:
      Our results show that p53 gene mutation may be associated with gastric
      carcinogenesis independent to H. pylori infection and absence of K-ras gene
      mutation questions its role in the pathogenesis of GC and PUD in Indian patients.

PMID- 23168709
TI  - Candida parapsilosis : an emerging fungal pathogen.

PMID- 23168710
TI  - Resistance to ceftriaxone in Vibrio cholerae.

PMID- 23168711
TI  - Daptomycin susceptibility of methicillin resistant Staphylococcus aureus (MRSA).

PMID- 23168712
TI  - Subcutaneous cysticercosis identified in chest radiography.

PMID- 23168714
TI  - Brucellar joint involvement presented with chest pain.

PMID- 23168715
TI  - Retraction.

PMID- 23168716
TI  - Studies on Shri Ramanand Yogi during his stay in an air-tight box. 1961.

PMID- 23168717
TI  - Fabrication of a dye-sensitized solar cell containing a Mg-doped TiO2 electrode
      and a Br3(-)/Br- redox mediator with a high open-circuit photovoltage of 1.21 V.
AB  - A dye-sensitized solar cell (DSSC) fabricated by using a Mg(2+)-doped anatase
      TiO(2) electrode with an alkoxysilyl dye and a Br(3)(-)/Br(-) electrolyte
      solution exhibited successfully a remarkably high open-circuit photovoltage over
      1.2 V, demonstrating a new possibility of DSSCs as practical photovoltaic
      devices.

PMID- 23168718
TI  - The role of resting frontal EEG asymmetry in psychopathology: afferent or
      efferent filter?
AB  - Resting EEG asymmetry evident early in life is thought to bias affective
      behaviors and contribute to the development of psychopathology. However, it
      remains unclear at what stage of information processing this bias occurs.
      Asymmetry may serve as an afferent filter, modulating emotional reactivity to
      incoming stimuli; or as an efferent filter, modulating behavioral response
      tendencies under emotional conditions. This study examines 209 kindergarten
      children (M = 6.03 years old) to test predictions put forth by the two models.
      Resting asymmetry was examined in conjunction with electrodermal and cardiac
      measures of physiological reactivity to four emotion-inducing film clips (fear,
      sad, happy, anger) and teacher ratings of psychopathology. Results confirm an
      association between increased right side cortical activation and internalizing
      symptom severity as well as left activation and externalizing symptom severity.
      Significant interactions between resting asymmetry and physiological reactivity
      to emotion indicate that physiological reactivity moderates the association
      between resting asymmetry and symptoms of psychopathology.

PMID- 23168719
TI  - Thoracoacromial artery perforators.

PMID- 23168721
TI  - Optical diagnosis for preneoplasia, the search continues.

PMID- 23168720
TI  - A retrospective study of complications of therapeutic plasma exchange in
      myasthenia.
AB  - INTRODUCTION: Venous access for therapeutic plasma exchange (TPE) in myasthenia
      gravis (MG) can be achieved by central venous catheters (CVC) or peripheral veins
      (PV), and the preferred method varies among providers. We evaluated our
      institutional experience with TPE venous access method and complications.
      METHODS: We reviewed all TPE-treated MG patients (2005-2010) through blinded
      chart review. TPE complications were categorized as serious or minor. Serious
      complications ended the procedure and/or were potentially life-threatening.
      RESULTS: A total of 134 MG patients received 230 TPE courses; 56% were outpatient
      procedures. Whenever feasible, TPE was performed by PV access, which was
      successful in 75% of courses. Over 90% in both groups improved after TPE.
      Compared with PV access, CVCs were associated with more total (68% vs. 35%) and
      serious complications (41% vs. 4%), including 2 deaths. CONCLUSIONS: PV access
      for TPE can be used successfully in most MG patients and may reduce morbidity of
      the procedure.

PMID- 23168722
TI  - Histology versus cytology in the diagnosis of lung cancer: is it a real
      advantage?

PMID- 23168723
TI  - How should we manage empyema complicating tunneled pleural catheter placement?

PMID- 23168724
TI  - Combining autofluorescence and narrow band imaging with image analysis in the
      evaluation of preneoplastic lesions in the bronchus and larynx.
AB  - BACKGROUND AND OBJECTIVES: Autofluorescence (AF) techniques improve the
      diagnostic yield of white light inspection for preneoplastic lesions in the
      bronchus and head and neck region. Although highly sensitive, AF has poor
      specificity, particularly in situations where there have been earlier biopsies or
      treatments such as radiotherapy. Narrow band imaging (NBI) is a newer imaging
      technique that enhances the early abnormal angiogenesis seen in preneoplastic
      lesions. NBI has higher specificity when compared with AF. We aimed to combine
      these imaging modalities, using AF as an effective screening tool and NBI to
      confirm AF findings. We also used computer-assisted image analysis techniques to
      give objective confirmation to our visual inspection. METHODS: Three patients
      were selected for image analysis of their NBI images using the L*a*b* color scale
      in manually drawn regions of interest of biopsy-confirmed areas. Each case
      compared pathology with a different benign condition: normal tissue, postbiopsy
      effect, and postradiation therapy change. Patients had white light followed by AF
      inspection. Abnormal areas of AF were cross-examined with NBI. RESULTS: NBI
      clearly showed dysplasia and carcinoma in situ. It also confirmed abnormal
      fluorescence because of earlier biopsies and radiation therapy. Analysis of the
      L*a*b* color space scale in each case showed segmentation between pathology and
      the benign tissue. CONCLUSIONS: There may be additive and discriminatory benefits
      of NBI after AF inspection. Further study with computer-assisted color
      segmentation techniques and image analysis is required before optical diagnosis
      can become a reality in bronchoscopic techniques in the future.

PMID- 23168725
TI  - The effect of cup versus alligator forceps on the results of transbronchial lung
      biopsy.
AB  - BACKGROUND: Transbronchial lung biopsy (TBLB) is a routine diagnostic procedure
      for pulmonary diseases and is performed by using either the alligator or cup
      forceps. The purpose of this study was to compare the role of the type of forceps
      in the quality and complications of TBLB. METHODS: This was a prospective,
      observational, double-blinded study. Four samples were taken from each patient
      through TBLB. Characteristics of the samples, including sample size and number of
      alveoli, whether it was diagnostic or not, and side effects such as pneumothorax
      and bleeding, were all recorded. RESULTS: One hundred seventy-six biopsy samples
      obtained from 44 patients were evaluated; 21 patients (47.7%) were male. Of the
      88 samples taken with an alligator forceps, based on size, 21.6% were small,
      45.5% were medium, and 33% were large. Corresponding results for the samples
      taken with a cup forceps were 43.2% small, 29.5% medium, and 27.3% large. Of the
      88 biopsy samples taken with an alligator forceps, 18.2% were diagnostic; this
      rate was 23.9% for cup forceps. Significant pneumothorax was not seen in any of
      the cases in the alligator forceps group, but it was detected in 9% of the cases
      in the cup forceps group. Significant bleeding was seen in 1% of the alligator
      forceps and 5.7% of the cup forceps procedures. CONCLUSIONS: Our study results,
      comparing the effect of 2 different kinds of forceps on TBLB results, were
      consistent with those of other studies with larger samples (P=0.008) using
      alligator forceps. The diagnostic value of the procedures was not significantly
      different (P=0.355).

PMID- 23168726
TI  - Endobronchial administration of tranexamic Acid for controlling pulmonary
      bleeding: a pilot study.
AB  - BACKGROUND: Tranexamic acid (TA) is a synthetic antifibrinolytic substance used
      for short-term control of bleeding. However, control of pulmonary bleeding with
      endobronchial administration of TA in more than 2 cases has not been attempted
      earlier. OBJECTIVE: We tested the feasibility of endobronchial administration of
      TA for controlling pulmonary bleeding. METHODS: This was a 2-year prospective
      observational trial of endobronchial TA in consecutive patients presenting with
      hemoptysis to our bronchoscopy unit. Patients were initially treated according to
      the recommendations of the Spanish National Guidelines using ice-cold saline and
      adrenaline. Endobronchial administration of TA was attempted in patients with
      uncontrolled hemoptysis before proceeding with further interventions (balloon
      occlusion or embolization). RESULTS: Forty-eight patients (37 male; mean age:
      64+/-13 y) were treated with endobronchial TA. The causes of bleeding were
      divided into iatrogenic (n=28) and noniatrogenic (n=20). Among patients with
      noniatrogenic bleeding, malignancies (11 patients) and bronchiectasis (10
      patients) were the most frequent causes of hemoptysis. In this patient group,
      endobronchial TA successfully controlled the bleeding in 11 subjects (39.2%).
      Nonresponders to endobronchial TA suffered more frequently from bronchiectasis
      (58.3% vs. 18.8%, P=0.039) and less frequently from malignancies (16.7% vs.
      56.3%, P=0.040) as compared with responders. All patients with iatrogenic
      bleeding were treated successfully with endobronchial TA. No subject in either of
      the patient groups suffered from thrombotic events or other adverse events
      related to endobronchial TA administration. CONCLUSIONS: Patients with acute
      pulmonary bleeding may benefit from endobronchial instillation of TA. Further
      double-blinded controlled studies are necessary to confirm our results.

PMID- 23168727
TI  - A pilot study of the feasibility of confocal endomicroscopy for examination of
      the human airway.
AB  - BACKGROUND: Traditional methods of evaluating human airway histology, such as
      surgical biopsy or endobronchial biopsy, are limited by the risks associated with
      these tissue-sampling procedures. OBJECTIVE: The purpose of this study was to
      develop and evaluate the first confocal endomicroscope for real-time, in vivo
      imaging of human respiratory mucosa in a clinical setting. METHODS: A confocal
      endomicroscope prototype was designed using Pentax bronchoscope parts (EB1970K).
      Airways of adult patients (N=5) undergoing rigid bronchoscopy for various
      clinical indications were imaged with the confocal endomicroscope after
      intravenous administration of fluorescein sodium. The device was introduced into
      the airways through the rigid bronchoscope. Images were collected from the
      trachea, primary and secondary carinae, and any endobronchial mass. The images
      were compared with those obtained from histologic sections from conventional
      endobronchial biopsies. RESULTS: Confocal endomicroscopy provided real-time
      images of the cellular and subcellular structures of the respiratory mucosa and
      submucosa in vivo. The pseudostratified columnar epithelium (including columnar
      cells and goblet cells) could be visualized. Images obtained at increasing depth
      showed the lamina propria and microvasculature. Longitudinal folds in the mucosa
      enabled imaging in cross-section, showing alignment of epithelial cells along the
      basement membrane and cilia on the surface of the cells. Below the epithelium,
      the smooth muscle could be identified. In images from a patient with an
      endobronchial adenocarcinoma, confocal imaging could distinguish between a normal
      airway epithelium and malignant tissue. CONCLUSIONS: Confocal endomicroscopy is a
      feasible method for analyzing human airway wall architecture and endobronchial
      abnormalities in histologic detail in vivo.

PMID- 23168728
TI  - Practice patterns for maintaining airway stents deployed for malignant central
      airway obstruction.
AB  - Although significant experience exists in placing airway stents, and knowledge of
      stent-related complications is widespread, information is lacking regarding
      methods of surveillance and maintaining patency of these stents. The purpose of
      this investigation was to determine the actual practice patterns used by
      interventional pulmonologists for airway stent maintenance. We prospectively
      surveyed members of the American Association of Bronchology and Interventional
      Pulmonology or attendees at their annual meeting during Chest 2008. Sixty-two
      respondents returned the completed surveys and were included in the analysis.
      Practice settings included university (50%), single specialty (27%), community
      academic (11%), and multispecialty (11%) settings. Annual placement of stents was
      <=10 (31%); 11 to 30 (45%); and >30 (24%). Considerable variability existed in
      both medications used for maintenance and surveillance schedules, and less than
      50% protocolized postplacement management. Although stent placement is common
      among experienced interventional pulmonologists, half have no protocol for
      surveillance or maintenance. Similarly, there is no discernable consistency or
      standard practice pattern to monitor for or prevent stent failure. Further study
      is required to determine the best practices for postdeployment surveillance and
      maintenance of airway stents.

PMID- 23168729
TI  - Pediatric Flexible Bronchoscopy in Singapore: A 10-year Experience.
AB  - AIM: To determine the results of children who underwent flexible bronchoscopy and
      bronchoalveolar lavage (BAL) in the Respiratory Medicine Service of Kandang
      Kerbau Women's and Children's Hospital from 1996 to 2005. METHOD: This was a
      retrospective study of all patients who underwent flexible bronchoscopy. Patients
      were traced from the hospital records. RESULTS: Two hundred and eight records
      were reviewed over a 10-year period. Of these, 63.5% were for male patients. The
      mean age of the patients was 4.1 years (range: 0.01 to 26 y). Sixty-six percent
      of the patients were below the age of 5 years. The main indications for
      bronchoscopy were abnormalities on chest x-ray (56.7%) followed by stridor
      (23.1%). An abnormality was detected in 77.7% of patients who underwent
      bronchoscopy. Twenty-three percent (n=45) of the bronchoscopes with BAL were
      performed on immunocompromised children for identification of microorganisms, of
      which 20% (n=9) yielded a positive microbiologic result. A positive yield was
      better if no earlier antimicrobials (26.3%) or only 1 antimicrobial was
      prescribed (42.8%) as compared with a 10% yield rate on treatment with 2 or more
      antimicrobials. The most common pathologic microorganisms identified were Candida
      albicans (18.5%) and Cytomegalovirus (18.5%). Complications from the bronchoscopy
      occurred in 16.6% of the patients. The main complication was hypoxia, which
      occurred in 28 children (13.4%). Other complications included cardiac arrhythmias
      (n=1, 0.5%) and laryngospasm (n=4, 1.9%). There were no fatalities experienced in
      our center. CONCLUSIONS: Flexible bronchoscopy was well tolerated with no serious
      adverse events being experienced. It is a useful tool in the investigation of
      stridor and persistent wheezing in children. For microbiologic identification,
      the BAL should be performed before initiating antimicrobials for better results.

PMID- 23168730
TI  - Anastomotic stenotic complications after tracheal resections.
AB  - BACKGROUND: Treatment of anastomotic stenosis after tracheal resections is not
      well established. We aimed to share our experience with the management of this
      condition. METHODS: This is a single-institution, retrospective study of
      prospectively recorded files of patients who suffered from anastomotic stenosis
      after tracheal resections. Data were analyzed according to the symptoms,
      location, length of the stenotic segments, and interventions. RESULTS:
      Anastomotic "restenosis" developed in 6 of 42 patients who had tracheal
      resections at our institute; and 6 patients were referred to us after restenosis
      of the initial resection performed elsewhere. Nine patients were admitted with
      the symptoms of dyspnea and stridor, 2 patients with surgical tracheostomy
      applied after unconsciousness, and 1 patient with a Montgomery T Tube (MTT). We
      treated 8 patients successfully with dilatation and therapeutic bronchoscopy
      including stent placement and re-resection. Four patients were palliated with
      MTT. CONCLUSIONS: Although the patient number was too small to draw any
      conclusions, we would like to stress that the MTT is still an acceptable option
      when therapeutic bronchoscopy fails and re-resection is technically not possible.

PMID- 23168731
TI  - "Black bronchoscopy"-a case of endobronchial metastases from melanoma.
AB  - The presence of black pigmentation in the airways during flexible bronchoscopy is
      uncommon. We report an unusual case of "black bronchoscopy" as a result of
      endobronchial metastases in a 77-year-old Chinese man, who presented with
      hemoptysis and postobstructive pneumonia 3 years after initial excision of a skin
      melanoma. Chest radiograph showed right lower lobe consolidation and collapse.
      Bronchoscopy showed narrowed airways with black pigmentation involving the lower
      trachea and right main bronchus. Biopsy confirmed metastatic melanoma. The
      patient received palliative radiation and died 6 months later. We review the
      causes of black airway pigmentation. We also briefly review the prevalence,
      clinical presentation, and prognosis of endobronchial metastases.

PMID- 23168732
TI  - Tracheobronchopathia osteochondroplastica.
AB  - A 71-year-old patient presented for cough, generalized body aches, and fever.
      Pulmonary work-up included computed tomography scan of the chest, which showed an
      irregular anterior tracheal wall. Flexible bronchoscopy showed the presence of
      multiple sessile nodules in the anterior and lateral walls of the trachea and
      mainstem bronchi, sparing the posterior membranous wall and the airways distal to
      the mainstem bronchi. Bronchoalveolar lavage grew Mycobacterium avium
      intracellulare and the patient was started on appropriate treatment. Biopsy of
      the lesions showed no malignancy or inflammation. An 18-month follow-up confirmed
      stability of these lesions pathognomonic of tracheobronchopathia
      osteochondroplastica, a rare benign condition of the large airways. Fewer than
      400 patients with this disorder have been described to date.

PMID- 23168733
TI  - Near-fatal hemorrhage after bronchoscopic resection of a carcinoid tumor:
      successful management by bronchial artery embolization.
AB  - A 36-year-old man presented with a large tracheal carcinoid just above the
      carina. The size and location precluded surgical treatment and so he underwent
      bronchoscopic tumor resection using electrocautery. After approximately 80% of
      tumor removal, brisk hemorrhage from the tumor stalk necessitated endotracheal
      intubation with anatomic lung separation and use of high cuff pressure to
      tamponade the bleeding site. This emergency measure was life saving, but
      extubation was not possible because of recurrence of bleeding whenever the
      tamponading cuff was deflated. Forty-eight hours later bronchial artery angiogram
      was performed to localize the bleeding site, and the vessels were successfully
      embolized using a gel foam. Cessation of bleeding facilitated successful
      extubation of the patient.

PMID- 23168734
TI  - Peripheral bronchopathia osteochondroplastica.
AB  - Tracheobronchopathia osteochondroplastica refers to the abnormal presence of
      osseous and/or cartilaginous nodules in the submucosa of the trachea and/or
      bronchi. This disease presents with exophytic lesions that are covered by normal
      mucosa. In this study, we report the case of a 51-year-old man who complained of
      exertional dyspnea. Chest x-ray and computed tomography showed diffuse bilateral
      micronodular pulmonary infiltrate. Mucosal appearance during bronchoscopy was
      completely normal. Histologic examination of the biopsy taken by transbronchial
      lung biopsy showed discrete cartilaginous nodules in the walls of the bronchiole.
      According to our investigation, this presentation of peripheral bronchopathia
      osteochondroplastica has not been reported previously.

PMID- 23168735
TI  - Multifocal endobronchial carcinoid tumors: a rare case.
AB  - We present a case of multifocal endobronchial carcinoid tumor and review the
      literature on multifocal endobronchial carcinoid tumors. Our patient was admitted
      with complaints of paroxysmal cough and recurrent lower respiratory tract
      infections. Computed tomography of the chest showed tubular densities in the
      bilateral lower lobes and a 15-mm soft-tissue mass in the right lower lobe
      without any enlargement in the mediastinal lymph nodes. On positron emission
      tomography scan, there was no fluorodeoxyglucose uptake in any of these lesions.
      Bronchoscopy showed multiple endobronchial tumors with hypervascularity. The
      pathologic examination of biopsies showed neuroendocrine neoplasm and typical
      bronchial carcinoid tumor. Although the only effective treatment for a bronchial
      carcinoid is complete surgical excision of the tumor, surgical resection was not
      performed in our patient because of multiple, bilateral, biopsy-proven
      endobronchial tumors. Radiation and chemotherapy are generally reserved for
      symptomatic and metastatic disease, which was the treatment of choice for our
      patient.

PMID- 23168736
TI  - Management of severe tracheal stenosis using flexible bronchoscopy and impulse
      oscillometry.
AB  - Although rigid bronchoscopy is the procedure of choice for interventional
      procedures of the proximal airway, flexible bronchoscopy can be used when lesions
      are not accessible by rigid equipment. We present an adolescent patient with
      tracheal stenosis whose airway was inaccessible through rigid bronchoscopy and
      thus required flexible bronchoscopy for all therapeutic procedures, including a
      stent placement. In addition, we describe our use of impulse oscillometry to
      monitor stent patency.

PMID- 23168737
TI  - Cerebral abscess: a rare complication of flexible bronchoscopy.
AB  - Infectious complications associated with flexible bronchoscopy are rare and
      mostly because of inadequate cleaning techniques. Transient bacteremia after
      flexible bronchoscopy has been observed; however, a clinically significant
      illness has been reported infrequently. We report the case of a 53-year-old man
      with poorly controlled diabetes who developed cerebral abscess 28 days after a
      flexible bronchoscopy was performed to evaluate a pneumonic consolidation of the
      left upper lobe of the lung. Streptococcus viridians was cultured from the
      cerebral abscess and the bronchoscopy specimens as well. Asymptomatic bacteremia
      from bronchoscopic procedures might have caused distant spread. Antibiotic
      treatment in susceptible patients for bacteremia may prevent serious infectious
      complications after flexible bronchoscopic procedures for infectious etiology.

PMID- 23168738
TI  - Pneumomediastinum after transbronchial lung biopsy.
AB  - Pneumomediastinum is a rare complication of a transbronchial lung biopsy. Common
      symptoms are chest pain, dyspnea, dysphagia, and specific electrocardiographic
      changes. We report a case of pneumomediastinum after a transbronchial lung
      biopsy. During the in-hospital stay, the symptoms and clinical picture rapidly
      improved without invasive treatment; therefore, the patient could be discharged
      after a few days. Approximately 1 month later, chest computed tomography was
      performed, which showed a complete resolution of the pneumomediastinum.

PMID- 23168739
TI  - Peripheral T-cell lymphoma with endobronchial involvement.
AB  - Peripheral T-cell lymphoma unspecified (PTCL-U) is a lymphoproliferative disorder
      characterized by localized malignant T-lymphocyte infiltration of the skin. PTCL
      U is a rare disease of the elderly with a low 5-year survival rate (16%). The
      skin is affected variably with localized plaques, nodules, or tumors. The lungs
      are involved in less than 10% of the cases. Nodules, masses, or mass-like
      consolidations are the most common pulmonary manifestations of PTCL-U. Pulmonary
      involvement by PTCL-U is associated with a poor prognosis. We report a case of
      PTCL-U presenting as an endobronchial and a parenchymal lesion before the skin
      manifestations. To our knowledge, this is the first report in the literature of
      pulmonary involvement preceding the dermatological manifestation of PTCL-U.

PMID- 23168740
TI  - A new technique of deploying dynamic y stent using flexible bronchoscope, video
      laryngoscope, and laryngeal mask airway.
AB  - Dynamic Y stents are used in tracheobronchial obstruction, tracheal stenosis, and
      tracheomalacia. Placement may be difficult and is usually accomplished using a
      rigid grasping forceps (under fluoroscopic guidance) or a rigid bronchoscope. We
      report using a new stent placement technique on an elderly patient with a central
      tracheobronchial tumor. It included using a flexible bronchoscope, video
      laryngoscope, and laryngeal mask airway. The new technique we used has the
      advantages of continuous direct endoscopic visualization during stent advancement
      and manipulation, and securing the airways with a laryngeal mask airway at the
      same time. This technique eliminates the need for intraoperative fluoroscopy.

PMID- 23168741
TI  - Endobronchial Carcinoid Tumor in an HIV-infected Patient.
AB  - Endobronchial carcinoid is an uncommon pulmonary neoplasm. In this brief report,
      we present a case of an HIV-infected patient with an incidentally identified
      endobronchial carcinoid. This case illustrates the importance of a broad
      differential diagnosis for lung lesions in HIV-infected patients.

PMID- 23168743
TI  - Endobronchial ultrasound in anthracosis.

PMID- 23168742
TI  - Techniques of linear endobronchial ultrasound imaging.
AB  - Endobronchial ultrasound is a minimally invasive technique that has found its
      application in the evaluation of mediastinal lymphadenopathy, intrapulmonary
      tumors and lung cancer staging. This article is aimed at clarifying the steps in
      the technique of visualization of the intrathoracic vascular structures and lymph
      node stations on linear endobronchial ultrasound imaging.

PMID- 23168744
TI  - Epiglottic hypoplasia.

PMID- 23168745
TI  - Regional specificity of manganese accumulation and clearance in the mouse brain:
      implications for manganese-enhanced MRI.
AB  - Manganese-enhanced MRI has recently become a valuable tool for the assessment of
      in vivo functional cerebral activity in animal models. As a result of the
      toxicity of manganese at higher dosages, fractionated application schemes have
      been proposed to reduce the toxic side effects by using lower concentrations per
      injection. Here, we present data on regional-specific manganese accumulation
      during a fractionated application scheme over 8 days of 30 mg/kg MnCl2 , as well
      as on the clearance of manganese chloride over the course of several weeks after
      the termination of the whole application protocol supplying an accumulative dose
      of 240 mg/kg MnCl2 . Our data show most rapid accumulation in the superior and
      inferior colliculi, amygdala, bed nucleus of the stria terminalis, cornu ammonis
      of the hippocampus and globus pallidus. The data suggest that no ceiling effects
      occur in any region using the proposed application protocol. Therefore, a
      comparison of basal neuronal activity differences in different animal groups
      based on locally specific manganese accumulation is possible using fractionated
      application. Half-life times of manganese clearance varied between 5 and 7 days,
      and were longest in the periaqueductal gray, amygdala and entorhinal cortex. As
      the hippocampal formation shows one of the highest T1 -weighted signal
      intensities after manganese application, and manganese-induced memory impairment
      has been suggested, we assessed hippocampus-dependent learning as well as
      possible manganese-induced atrophy of the hippocampal volume. No interference of
      manganese application on learning was detected after 4 days of Mn(2+) application
      or 2 weeks after the application protocol. In addition, no volumetric changes
      induced by manganese application were found for the hippocampus at any of the
      measured time points. For longitudinal measurements (i.e. repeated manganese
      applications), a minimum of at least 8 weeks should be considered using the
      proposed protocol to allow for sufficient clearance of the paramagnetic ion from
      cerebral tissue.

PMID- 23168747
TI  - Our wages of CIN.

PMID- 23168748
TI  - The Affordable Care Act: an overview for obstetricians and gynecologists.

PMID- 23168749
TI  - Maternal and neonatal outcomes of dose-dense chemotherapy for breast cancer in
      pregnancy.
AB  - OBJECTIVE: To estimate the effect of dose-dense chemotherapy during pregnancy on
      maternal and neonatal outcomes. METHODS: This is a retrospective cohort study in
      which women were identified from the international Cancer and Pregnancy Registry
      at Cooper Medical School at Rowan University in Camden, New Jersey. A chart
      analysis was completed and Fisher's exact test and independent t test were used
      in comparing patient outcomes. RESULTS: Ten women received dose-dense
      chemotherapy, received every 2 weeks, and 99 women received conventional
      chemotherapy, received with at least 3-week intervals, for breast cancer during
      pregnancy. Birth weight, gestational age at delivery, rate of growth restriction,
      congenital anomalies, and incidence of maternal and neonatal neutropenia were not
      statistically different between the two groups. CONCLUSION: In the small cohort
      of women in our registry, dose-dense chemotherapy does not appear to increase the
      risk of fetal or maternal complications.

PMID- 23168750
TI  - Hospital discharge on the first compared with the second day after a planned
      cesarean delivery: a randomized controlled trial.
AB  - OBJECTIVES: To compare patient satisfaction and exclusive breastfeeding rates for
      patients discharged from the hospital on postcesarean day 1 (next day) or day 2.
      METHODS: Healthy women admitted for planned cesarean delivery were randomized to
      day 1 or day 2 discharge. Postoperative assessment for suitability for discharge
      was based on defined criteria. Primary outcomes were patient satisfaction with
      their discharge timing assessed at 2 weeks and reported exclusive breastfeeding
      at 6 weeks after discharge. Analyses were based on intention-to-treat and per
      protocol discharge. RESULTS: Of the 360 women randomized, results of 170 compared
      with 172 and 142 compared with 148 (day 1 compared with day 2) were available for
      intention-to-treat and per-protocol analyses, respectively. Nine women fulfilled
      discharge criteria but declined day 1 discharge, and 12 women allocated to day 2
      discharge took their own discharge on day 1. Intention-to-treat analysis showed
      that satisfaction with discharge protocol was expressed by 148 of 170 (87.1%)
      compared with 147 of 172 (85.5%) (relative risk 1.1, 95% confidence interval [CI]
      0.6-2.1, P=.75) and exclusive breastfeeding (at 6 weeks) was reported by 76 of
      170 (44.7%) compared with 77 of 172 (44.9%) (relative risk 1.0 95% CI 0.7-1.5
      P=.99 for day 1 compared with day 2 discharges, respectively). All secondary
      outcomes assessed at up to 6 weeks after discharge including unscheduled maternal
      or infant medical consultations, rehospitalizations, maternal antibiotic use, and
      maternal well-being, anxiety, and depression status, were similar. Results on per
      protocol analysis were also similar. CONCLUSION: Day 1 discharge compared with
      day 2 discharge after a planned cesarean delivery resulted in equivalent
      outcomes. CLINICAL TRIAL REGISTRATION: ISRCTN Register, ISRCTN.org,
      ISRCTN27523895.

PMID- 23168751
TI  - Maternal, perinatal, and postneonatal outcomes in women with chronic heart
      disease in Washington State.
AB  - OBJECTIVE: To explore the association between the presence of maternal heart
      disease and maternal, perinatal, and infant outcomes. METHODS: We conducted a
      population-based retrospective cohort study using Washington State birth
      certificates linked with hospital discharge records of mothers noted to have
      maternal congenital heart disease, ischemic heart disease, heart failure, or
      pulmonary hypertension. Women who gave birth between 1987 and 2009 (n=2,171) were
      compared with a sample of mothers without these conditions (n=21,710). We
      described characteristics of pregnant women with heart disease over time.
      Logistic regression estimated the association between chronic maternal heart
      disease and small-for-gestational-age (SGA) neonates as well as perinatal,
      postneonatal, and maternal death. RESULTS: The proportion of births to women with
      reported heart disease increased 224% between the 1987 and 1994 and 2002 and 2009
      calendar periods. Chronic maternal heart disease was associated with increased
      risk of SGA (62 additional SGA newborns per 1,000 births, 95% confidence interval
      [CI] 46-78; P<.001), perinatal death (14 additional deaths per 1,000 births, 95%
      CI 8-20; P<.001), postneonatal death (5 additional deaths per 1,000 births, 95%
      CI 2-9; P<.001), and maternal death (5 additional deaths per 1,000 births, 95% CI
      2-9; P<.001). CONCLUSION: The presence of chronic maternal heart disease is
      associated with elevated risk for poor maternal, perinatal, and postneonatal
      outcomes.

PMID- 23168752
TI  - Preventing unintended pregnancies by providing no-cost contraception.
AB  - OBJECTIVE: To promote the use of long-acting reversible contraceptive (LARC)
      methods (intrauterine devices [IUDs] and implants) and provide contraception at
      no cost to a large cohort of participants in an effort to reduce unintended
      pregnancies in our region. METHODS: We enrolled 9,256 adolescents and women at
      risk for unintended pregnancy into the Contraceptive CHOICE Project, a
      prospective cohort study of adolescents and women desiring reversible
      contraceptive methods. Participants were recruited from the two abortion
      facilities in the St. Louis region and through provider referral, advertisements,
      and word of mouth. Contraceptive counseling included all reversible methods but
      emphasized the superior effectiveness of LARC methods (IUDs and implants). All
      participants received the reversible contraceptive method of their choice at no
      cost. We analyzed abortion rates, the percentage of abortions that were repeat
      abortions, and teenage births. RESULTS: We observed a significant reduction in
      the percentage of abortions that were repeat abortions in the St. Louis region
      compared with Kansas City and nonmetropolitan Missouri (P<.001). Abortion rates
      in the CHOICE cohort were less than half the regional and national rates
      (P<.001). The rate of teenage birth within the CHOICE cohort was 6.3 per 1,000,
      compared with the U.S. rate of 34.3 per 1,000. CONCLUSION: We noted a clinically
      and statistically significant reduction in abortion rates, repeat abortions, and
      teenage birth rates. Unintended pregnancies may be reduced by providing no-cost
      contraception and promoting the most effective contraceptive methods.

PMID- 23168753
TI  - Continuation of reversible contraception in teenagers and young women.
AB  - OBJECTIVE: To examine the effect of age on continuation rates of reversible
      contraceptive methods among females aged 14-19 years and women aged 20-25 years
      compared with women older than 25 years of age. METHODS: We analyzed data from
      7,472 participants enrolled in the Contraceptive CHOICE Project, a prospective
      cohort study of women offered no-cost contraception. Our primary objective was to
      compare 12-month continuation rates between females aged 14-19, 20-25, and 26
      years and older. We collected data about method continuation from telephone
      surveys and chart review. We used Kaplan-Meier survival curves to estimate
      continuation and Cox proportional hazard models to examine the risk of
      contraceptive method discontinuation. RESULTS: Twelve-month continuation of long
      acting reversible contraceptive (LARC) methods was more than 75% for all age
      groups. Females aged 14-19 years using LARC methods had slightly lower
      continuation rates (81%) than older women (85-86%), but this did not reach
      statistical or clinical significance. Compared with women older than 25 years of
      age, females aged 14-19 years had higher discontinuation rates for non-LARC
      methods (53% compared with 44%; adjusted hazard ratio 1.32, 95% confidence
      interval [CI] 1.02-1.73). The females aged 14-19 years were less likely to be
      satisfied with non-LARC methods (42% compared with 51%; adjusted relative risk
      0.80, 95% CI 0.65-0.98), but not with LARC methods (75% compared with 83%;
      relative risk 0.94, 95% CI 0.88-1.01) when compared with women older than 25
      years of age; however, the differences were small. CONCLUSION: Teenagers and
      young women have high rates of LARC method continuation.

PMID- 23168754
TI  - Effect of sexual debut on vaginal microbiota in a cohort of young women.
AB  - OBJECTIVE: Bacterial vaginosis is uncommon in women who are virgins. We estimated
      effects of sexual debut on vaginal bacterial colonization. METHODS: Women who
      were virgins and aged 18-22 years enrolled in a study of human papillomavirus
      acquisition were followed every 4 months for up to 2 years. Vaginal swabs from
      before and after sexual debut or two independent visits for those remaining
      virgins were tested by quantitative polymerase chain reaction for Lactobacillus
      crispatus, Lactobacillus jensenii, Lactobacillus iners, Gardnerella vaginalis,
      and the bacterial vaginosis-associated species Atopobium vaginae, Megasphaera
      species, Leptotrichia species, Sneathia species, and bacterial vaginosis
      associated bacterium-1, -2, and -3. RESULTS: We evaluated 97 women: 71 who became
      sexually active and 26 who remained virgins. At first sampling, 22 of 26 (85%)
      women who remained virgins were colonized with Lactobacillus species compared
      with 22 of 26 (85%) at follow-up (P>.99). G vaginalis was present in 12 of 26
      (46%) initially and 11 of 26 (42%) at follow-up (P>.99). Among women who became
      sexually active, colonization with Lactobacillus species remained stable: 65 of
      71 (92%) compared with 66 of 71 (93%) (P>.99), whereas colonization with G
      vaginalis increased (28 of 71 [39%] compared with 40 of 71 [56%]; P=.02). Among
      women who did not initiate sexual activity during the study, two of 26 (8%) had
      any bacterial vaginosis-associated species detected at both the first and second
      visits (P>.99). Among women who became sexually active during the study, 15 of 71
      (21%) were colonized with bacterial vaginosis-associated species initially
      compared with 13 of 71 (18%) after sexual debut (P=.77). CONCLUSIONS: Among women
      who were virgins, vaginal colonization with bacterial vaginosis-associated
      bacterial species is uncommon and does not change after sexual debut.

PMID- 23168755
TI  - Neisseria gonorrhea and Chlamydia trachomatis screening at intrauterine device
      insertion and pelvic inflammatory disease.
AB  - OBJECTIVE: To evaluate the relationship between Neisseria gonorrhea and Chlamydia
      trachomatis screening strategies and risk of pelvic inflammatory disease (PID)
      after intrauterine device (IUD) insertion. METHODS: We conducted a retrospective
      cohort study of all IUD insertions at Kaiser Permanente Northern California from
      January 2005 to August 2009. The PID incidence within 90 days after insertion was
      compared among women who were and were not screened for N gonorrhea and C
      trachomatis. The study was powered for equivalence with a PID risk difference of 
      0.006 to 0.006 between two groups considered to be clinically insignificant. Risk
      difference was calculated by subtracting the proportion of females with PID in
      one screening group from the proportion of females with PID in the comparison
      screening group. RESULTS: Of 57,728 IUD insertions, 47% were unscreened within 1
      year of insertion; of screened women, 19% were screened on the same day. The
      overall risk of PID was 0.54% (95% confidence interval [CI] 0.48-0.60%).
      Nonscreening had an equivalent risk of PID as any screening (risk difference 
      0.0034, 95% CI -0.0045 to -0.0022), and same-day screening was equivalent to
      prescreening (risk difference -0.0031, 95% CI -0.0049 to -0.0008). The
      equivalence persisted when adjusted for age and race and when stratified by age
      younger than 26 years and older than 26 years. CONCLUSION: The risk of PID in
      women receiving IUDs was low. These results support IUD insertion protocols in
      which clinicians test women for N gonorrhea and C trachomatis based on risk
      factors and perform the test on the day of insertion. These findings have
      potential to reduce barriers to IUD use for women seeking highly effective, long
      term, reversible contraception.

PMID- 23168756
TI  - Nifedipine compared with atosiban for treating preterm labor: a randomized
      controlled trial.
AB  - OBJECTIVE: To compare the tocolytic efficacy and tolerability of nifedipine with
      that of atosiban among pregnant women with preterm labor. METHODS: Pregnant women
      admitted with preterm labor and intact membranes between 24 and 33 weeks 6 days
      of gestation, between January 2008 and December 2011, were randomly assigned to
      either atosiban or nifedipine treatment. Assigned treatment was planned for up to
      48 hours. If progress was determined after 1 hour or more, a crossover of the
      study drugs was performed. The primary outcome was to estimate the tocolytic
      efficacy and tolerability profile that was assessed in terms of the proportion of
      women who were not delivered and did not require an alternate tocolytic agent
      within 48 hours. Secondary outcomes were gestational age at delivery and neonatal
      morbidity. RESULTS: Seventy-five women in the nifedipine group and 70 in the
      atosiban group were included and analyzed. Baseline demographic and obstetric
      characteristics were comparable. Forty-eight (68.6%) women allocated to atosiban
      and 39 (52%) to nifedipine did not deliver and did not require an alternate agent
      at 48 hours respectively (P=.03). At 7 days from enrollment, 55 (78.6%) women
      allocated to atosiban and 67 (89.3%) to nifedipine remained undelivered with or
      without a rescue agent (P=.02). Mean gestational age at delivery was 35.2 (+/
      3.0) and 36.4 (+/-2.8) weeks among the atosiban and nifedipine groups,
      respectively (P=.01). Mean birth weight and neonatal morbidity were comparable.
      CONCLUSIONS: Atosiban has fewer failures within 48 hours. Nifedipine may be
      associated with a longer postponement of delivery. CLINICAL TRIAL REGISTRATION:
      ClinicalTrials.gov, www.clinicaltrials.gov, NCT00599898.

PMID- 23168758
TI  - Application of second-stage passive descent in morbidly obese women.
AB  - OBJECTIVE: To estimate whether passive descent in the second stage of labor in
      morbidly obese parturients is associated with reduced active pushing times and
      improved labor outcomes compared with immediate pushing. METHODS: This was a
      retrospective cohort study of all consecutive women with a body mass index (BMI)
      of 40 or greater admitted for term labor that reached the second stage of labor
      from 2004 to 2008 at a single institution. Detailed information was collected for
      maternal demographics, labor progress, and neonatal outcomes. Length of active
      pushing, length of total second stage, and maternal and neonatal outcomes were
      compared between women selected to passive descent for at least 30 minutes and
      those who pushed immediately. RESULTS: A total of 558 women with a BMI of 40 or
      greater were identified; of these, 97 underwent passive descent and 461 pushed
      immediately. Morbidly obese women selected for passive descent were just as
      likely to actively push for at least 60 minutes compared with those who pushed
      immediately (16.5% compared with 7.2%, adjusted odds ratio [OR] 1.51, 95%
      confidence interval [CI] 0.74-3.12). They were also significantly more likely to
      push for more than 30 minutes (37.1% compared with 13.9%, adjusted OR 2.03, 95%
      CI 1.17-3.54). Their overall time (minutes) spent pushing was significantly
      longer (median 19, interquartile range 7-39 compared with median 7, interquartile
      range 3-17, P<.001) as was their overall length of second stage (median 81,
      interquartile range 57-127 compared with median 15, interquartile range 8-27,
      P<.001). They had similar rates of operative delivery and maternal febrile
      morbidity. CONCLUSION: Passive descent of morbidly obese parturients was
      associated with a greater amount of time actively pushing with similar rates of
      operative delivery and maternal febrile morbidity.

PMID- 23168759
TI  - Epidemiology, natural history, progression, and postnatal outcome of severe fetal
      ventriculomegaly.
AB  - OBJECTIVE: To estimate the prevalence, associated anomalies, progression, and
      clinical outcome in fetuses prenatally diagnosed with severe ventriculomegaly.
      METHODS: This is a population-based study using prospectively collected data from
      the north of England. Data were obtained from the Northern Congenital Abnormality
      Survey for the period 1994-2008. Associated anomalies were categorized using the
      European Surveillance of Congenital Anomalies guidelines. Differences between
      isolated and nonisolated ventriculomegaly were examined using Fisher's exact test
      or Mann-Whitney U test. RESULTS: There were 157 cases of confirmed severe
      ventriculomegaly in singleton pregnancies among 441,247 eligible births, a
      prevalence of 3.6 per 10,000 births (95% confidence interval [CI] 3.0-4.2).
      Chromosomal anomalies were detected prenatally in five cases (3.2%, 95% CI 1.0
      7.3) and associated structural anomalies in 67 (42.7%, 95% CI 34.8-50.8). One
      hundred one women (64.3%) elected to have a termination of pregnancy, more
      commonly in the presence of associated anomalies (76.9% compared with 51.9%,
      P=.001). Ultrasonographic follow-up data were available for 53 fetuses; in 13
      cases (24.5%), atrium size decreased prenatally, whereas in the remainder, median
      atrium size increased by 4.1 mm over 3.5 weeks. Associated anomalies were
      detected postnatally in 22 of 79 cases suspected prenatally to be isolated
      (27.8%, 95% CI 18.3-39.1). Of 53 live births, there were 11 (20.8%) neonatal
      deaths, including six (16.2%) of the isolated group. Neonatal death was not
      predicted by atrial measurement progression. CONCLUSION: The prevalence of severe
      ventriculomegaly was 3.6 per 10,000 births. Although more than 50% opt to
      terminate, of those with live births, there were 21% neonatal deaths with nearly
      half in neonates with isolated ventriculomegaly.

PMID- 23168757
TI  - Risk of uterine rupture and placenta accreta with prior uterine surgery outside
      of the lower segment.
AB  - OBJECTIVE: Women with a prior myomectomy or prior classical cesarean delivery
      often have early delivery by cesarean because of concern for uterine rupture.
      Although theoretically at increased risk for placenta accreta, this risk has not
      been well-quantified. Our objective was to estimate and compare the risks of
      uterine rupture and placenta accreta in women with prior uterine surgery.
      METHODS: Women with prior myomectomy or prior classical cesarean delivery were
      compared with women with a prior low-segment transverse cesarean delivery to
      estimate rates of both uterine rupture and placenta accreta. RESULTS: One hundred
      seventy-six women with a prior myomectomy, 455 with a prior classical cesarean
      delivery, and 13,273 women with a prior low-segment transverse cesarean delivery
      were evaluated. Mean gestational age at delivery differed by group (P<.001),
      prior myomectomy (37.3 weeks), prior classical cesarean delivery (35.8 weeks),
      and low-segment transverse cesarean delivery (38.6 weeks). The frequency of
      uterine rupture in the prior myomectomy group (P-MMX group) was 0% (95%
      confidence interval [CI] 0-1.98%). The frequency of uterine rupture in the low
      segment transverse cesarean delivery group (LTC group) (0.41%) was not
      statistically different from the risk in the P-MMX group (P>.99) or in the prior
      classical cesarean delivery group (PC group) (0.88%; P=.13). Placenta accreta
      occurred in 0% (95% CI 0-1.98%) of the P-MMX group compared with 0.19% in the LTC
      group (P>.99) and 0.88% in the PC group (P=.01 relative to the LTC group). The
      adjusted odds ratio for the PC group (relative to LTC group) was 3.23 (95% CI
      1.11-9.39) for uterine rupture and 2.09 (95% CI 0.69-6.33) for accreta. The
      frequency of accreta for those with previa was 11.1% for the PC group and 13.6%
      for the LTC group (P>.99). CONCLUSION: A prior myomectomy is not associated with
      higher risks of either uterine rupture or placenta accreta. The absolute risks of
      uterine rupture and accreta after prior myomectomy are low.

PMID- 23168760
TI  - Outpatient vaginal hysterectomy: optimizing perioperative management for same-day
      discharge.
AB  - OBJECTIVE: To present tactics for optimizing outpatient vaginal hysterectomy and
      describe perioperative outcomes in a large consecutive case series. METHODS: This
      is a descriptive study and review of clinical outcomes in 1,071 patients selected
      to undergo vaginal hysterectomy for benign indications from 2000 to 2010. The
      setting is a single-surgeon private practice in a community hospital. Outcome
      measures include length of hospital stay, estimated blood loss, operative time,
      uterine weight, and perioperative complications, including hospital readmissions
      and emergency room visits. RESULTS: One thousand seventy-one of 1,162 cases (92%,
      95% confidence interval [CI] 90.5-93.7) were total vaginal hysterectomies, of
      which 1,029 (96%, 95% CI 94.9-97.3) were discharged the same day after surgery.
      The median operative time was 34 minutes (range 17-210 minutes), and estimated
      blood loss was 45 mL (range 5-800 mL). The median patient age was 46 years (range
      27-86 years), and median uterine weight was 160 g (range 25-1,380 g). One hundred
      ninety-three patients (18%, 95% CI 15.8-20.5) were nulliparous and 218 (20%, 95%
      CI 18-22.9) had prior pelvic surgery. Five patients (0.5%, 95% CI 0.2-1.1)
      required readmission or emergency room evaluation within the first 30 days.
      CONCLUSION: Vaginal hysterectomy can be successfully adopted as a same-day
      discharge procedure. In this population, regardless of previous pelvic surgery or
      nulliparity, good perioperative outcomes have been achieved.

PMID- 23168761
TI  - Utility of cystoscopy during hysterectomy.
AB  - OBJECTIVE: To estimate the incidence of cystoscopy use at time of hysterectomy
      and its use to detect urinary tract injury. METHODS: This was a retrospective
      cohort study in a tertiary care academic center of 1982 patients who underwent a
      hysterectomy for any indication (excluding obstetric) between January 2009 and
      December 2010. Medical records were reviewed for baseline and perioperative
      characteristics, cystoscopy use, and information about bladder or ureteral injury
      related to hysterectomy. RESULTS: Two hundred fifty-one women (12.66%, 95%
      confidence interval [CI] 11.23-14.21%) underwent a cystoscopy at the time of
      hysterectomy with no reported complications resulting from the cystoscopy
      procedure. Cystoscopy was most frequently used by low-volume surgeons and in
      cases involving prolapse or vaginal mode of access. Fourteen patients (0.71%, 95%
      CI 0.39-1.19%) experienced bladder injury and five patients (0.25%, 95% CI 0.08
      0.58%) sustained ureteral injury. None of these complications were detected by
      cystoscopy; cystoscopy was either normal at the time of hysterectomy or was
      omitted. The presence of adhesions was significantly associated with bladder
      injury at the time of hysterectomy (P=.006). Low-volume surgeon and laparoscopic
      or robotic mode of access were both significantly associated with ureteral injury
      (P=.023 and P=.042, respectively). CONCLUSIONS: Our data support selective rather
      than universal cystoscopy at the time of hysterectomy.

PMID- 23168762
TI  - Pure compared with mixed serous endometrial carcinoma: two different entities?
AB  - OBJECTIVE: To analyze whether mixed compared with pure uterine papillary serous
      carcinoma histology affects clinical outcome, and to assess uterine papillary
      serous carcinoma for its association with the precursor lesion endometrial
      intraepithelial carcinoma. METHODS: A multi-institution observational study of
      stage I-IV uterine papillary serous carcinoma patients was performed.
      Histopathologic slides were reviewed by four expert pathologists, with
      determination of the percentage serous histology within each tumor. The pre
      existent endometrium was evaluated for the presence of endometrial
      intraepithelial carcinoma. RESULTS: We included 108 uterine papillary serous
      carcinoma patients. Fifty-eight patients had mixed and 50 patients had pure
      uterine papillary serous carcinoma histology. On multivariable analysis, advanced
      International Federation of Gynecology and Obstetrics (FIGO) stage (hazard ratio
      [HR] 3.15, 95% confidence interval [CI] 1.57-6.32), mixed uterine papillary
      serous carcinoma histology (HR 0.35, 95% CI 0.19-0.66), and lymphovascular space
      invasion (HR 2.10, 95% CI 1.07-4.16) were significantly associated with
      recurrence. International Federation of Gynecology and Obstetrics stage (HR 4.67,
      95% CI 2.25-9.70) and mixed uterine papillary serous carcinoma histology (HR
      0.39, 95% CI 0.20-0.76) were significantly and independently associated with
      survival. Endometrial intraepithelial carcinoma was identified in 83.9% of all
      cases, with no significant difference between mixed and pure uterine papillary
      serous carcinoma patients. Atrophic or weakly proliferative endometrium was found
      in 90.7% of pure uterine papillary serous carcinoma cases, whereas hyperplastic
      endometrium with atypia was more commonly found in 34.7% of mixed carcinoma
      patients with uterine papillary serous carcinoma (P=.004). CONCLUSION: Pure
      uterine papillary serous carcinoma histology and FIGO stage are the most
      important risk factors for recurrence and survival in patients with uterine
      papillary serous carcinoma. Adjusted for covariates, patients with pure uterine
      papillary serous carcinoma had a 2.9-times greater risk for recurrence and a 2.6
      times higher risk of death compared with patients with mixed uterine papillary
      serous carcinoma. Furthermore, endometrial intraepithelial carcinoma was equally
      found among pure and mixed uterine papillary serous carcinoma cases, whereas the
      nonneoplastic endometrium was atrophic or weakly proliferative in pure uterine
      papillary serous carcinoma cases compared with more hyperplastic endometrium with
      atypia in mixed uterine papillary serous carcinoma cases.

PMID- 23168763
TI  - Improving the selection of recommended prophylactic antibiotics using an
      electronic medical record.
AB  - OBJECTIVE: To estimate the effect of reference text in an electronic medical
      record (EMR) on the recommended use of preoperative antibiotics for cesarean
      deliveries. METHODS: A retrospective cohort study of all cesarean deliveries at
      Stony Brook Hospital between May 2009 and June 2011, was performed. Reference
      text was added to the EMR in May 2010. The cesarean deliveries performed before
      (group 1) and after (group 2) the addition of the reference text were compared
      for the type and dose of antibiotic ordered preoperatively, as well as the
      patient's body mass index (BMI), drug allergies, and diagnosis of
      chorioamnionitis. Those with chorioamnionitis were excluded. The chi and t tests
      were performed to study differences between the groups. RESULTS: Of the 2,273
      deliveries identified, 172 were excluded for chorioamnionitis or incomplete
      medical records. The women in group 1 had a higher BMI (33.3 +/- 7.3 kg/m2)
      compared with the women in group 2 (32.6 +/- 6.3 kg/m2; P=.005). Otherwise, there
      were no differences between the groups regarding maternal weight, penicillin
      allergy, or other antibiotics. There was a significant increase in the number of
      patients receiving the adequate (92.6% compared with 85.7%; P<.005) and
      recommended (58.1% compared with 43.4%; P<.005) antibiotics in group 2 when
      compared with group 1. CONCLUSION: Reference text included within the EMR that
      prompts physicians to select the recommended antibiotics significantly improves
      preoperative antibiotic use.

PMID- 23168764
TI  - Association of atypical decelerations with acidemia.
AB  - OBJECTIVE: To estimate the incidence of atypical fetal heart rate deceleration
      characteristics in term labor and their association with acidemia. METHODS: A 5
      year retrospective cohort study was performed of all singleton, nonanomalous
      gestations delivered at 37 weeks or after. Thirty minutes of electronic fetal
      monitoring before delivery were interpreted by two formally trained research
      nurses, blind to clinical and outcome data, using American College of
      Obstetricians and Gynecologists (the College) guidelines as well as deceleration
      features historically referred to as atypica such as shoulders, slow return, and
      variability within the deceleration. Acidemia was defined as umbilical cord
      arterial pH 7.10 or less. Incidence of atypical features was estimated;
      univariable and multivariable analyses were performed. RESULTS: Within 5,388
      women, the atypical feature seen with the most frequency was shoulders (n=2,914
      [54.1%]) followed by slow return (n=2,618 [48.6%]), minimal deceleration
      variability (n=430 [8.0%]), and absent deceleration variability (n=4 [0.07%]).
      There was no difference in the incidence of atypical features between neonates
      with acidemia (n=57) and without (n=5,331). There was no association between
      shoulders (adjusted odds ratio [OR] 1.06, 95% confidence interval [CI] 0.63-1.81)
      or slow returns (adjusted OR 0.91, 95% CI 0.54-1.53) and acidemia. Similarly,
      compared with patients with moderate variability within deceleration nadirs,
      neither minimal (adjusted OR 0.82, 95% CI 0.43-1.55) nor marked (adjusted OR
      0.65, 95% CI 0.27-1.55) variability was significantly associated with acidemia.
      CONCLUSION: These data support the absence of these specific atypical
      deceleration characteristics from the recognized definitions of decelerations
      stipulated by the College and the Eunice Kennedy Shriver National Institute of
      Child Health and Human Development in 2008 given their lack of association with
      acidemia or neonatal depression.

PMID- 23168765
TI  - Effect of maternal cystic fibrosis genotype on diabetes in pregnancy.
AB  - OBJECTIVE: To evaluate the association between the cystic fibrosis (CF) genotype
      and the rate of diabetes complicating pregnancy. METHODS: We conducted a
      retrospective cohort analysis of all pregnant patients with CF from 1972-2011 at
      a single institution. Patients who were homozygous for the DeltaF508 mutation
      were compared with patients who were heterozygous for the DeltaF508 mutation.
      Primary outcomes measured were incidence of CF-related diabetes and gestational
      diabetes mellitus (GDM) stratified by CF genotype. Secondary outcomes measured
      included pancreatic insufficiency, preterm premature rupture of membranes,
      preterm delivery, mode of delivery, gestational age at delivery, and maternal
      mortality. RESULTS: We identified 54 pregnancies among 36 women who met inclusion
      criteria. Of these pregnancies, 28 (51.9%) were carried by women who were
      homozygous for the DeltaF508 mutation. Homozygous women had a significantly
      greater incidence of pancreatic insufficiency (89.3% compared with 61.5%, P=.03)
      and diabetes complicating pregnancy (60.7% compared with 23.1%, P<.01) compared
      with heterozygous women. In addition, there was some evidence of an increased
      incidence of GDM specifically among homozygous women (35.7% compared with 15.4%,
      P=.12). Regarding neonatal outcome, there was a lower mean birthweight (2,881 g
      compared with 3,203 g, P=.04) among the women who were homozygous for the
      DeltaF508 mutation. There was no statistical difference in preterm deliveries,
      mode of delivery, gestational age at delivery, rate of preterm premature rupture
      of membranes, or incidence of maternal mortality between the two groups.
      CONCLUSION: Women with CF who are homozygous for the DeltaF508 mutation have an
      increased risk of having a pregnancy complicated by diabetes.

PMID- 23168766
TI  - Management of intravenous leiomyomatosis with intracaval and intracardiac
      extension.
AB  - OBJECTIVE: To report the results of management of intravenous leiomyomatosis with
      intracaval and intracardiac extension at Peking Union Medial College Hospital.
      METHODS: We reviewed a cohort of 20 patients with intravenous leiomyomatosis
      extending to the inferior vena cava and heart, focusing on the clinical
      characteristics, the results of surgical management, and prognosis. RESULTS: The
      mean age of the patients was 42.4 +/- 7.0 years. The clinical manifestations of
      intravenous leiomyomatosis are various and nonspecific, including pelvic mass,
      chest tightness and shortness of breath, swelling in the lower extremity,
      abdominal distension, palpitation, syncope, hypermenorrhea, and skelalgia. All
      the patients had history of uterine leiomyoma and 16 patients (80%) had undergone
      uterine leiomyoma operation. After careful preoperative evaluation, nine patients
      underwent one-stage operations (cardiac surgery, vascular and gynecologic surgery
      together) and 11 patients underwent two-stage operations (cardiac surgery first,
      then vascular and gynecologic surgery). There was no significant difference in
      the postoperative complication rate (33.3% compared with 27.3%; P>.99) between
      one-stage and two-stage operations. All operations were performed without severe
      surgical-related complications or death. Approximately 78% of patients had
      complete resection of tumor and 22.2% of the patients experienced incomplete
      resection. Eleven (55%) patients received hormone therapy postoperatively. During
      mean follow-up time of 20.5 months, recurrence occurred in five patients (27.8%)
      but all the patients survived. CONCLUSIONS: Precise and full-scale preoperative
      evaluation, complete tumor resection, and multidisciplinary cooperation are
      crucial for successful treatment.

PMID- 23168767
TI  - Fluconazole-resistant Candida albicans vulvovaginitis.
AB  - OBJECTIVE: As a result of high recurrence rates of Candida albicans vaginitis,
      successful suppressive fluconazole is widely used, and drug resistance is
      considered rare. We report increased occurrence of secondary fluconazole
      resistance, analysis of risk factors thereof, and describe management of
      fluconazole-refractory vaginitis. METHODS: Patients referred to the Vaginitis
      Clinic at Wayne State University with clinically refractory fluconazole-resistant
      (minimum inhibitory concentration [MIC] 2 micrograms/mL or greater) C albicans
      vaginitis from 2000 to 2010 were enrolled. Patients completed a questionnaire
      pertaining to demographics, comorbidities, behavioral characteristics, exposure
      to antimicrobials and antifungals, fluconazole consumption in defined daily doses
      in the previous 6 months, management received, and outcomes. With patients not
      located, data were extracted from charts. Susceptibilities to antifungals were
      determined by broth microdilution. RESULTS: Twenty-five women with fluconazole
      resistant recurrent C albicans vaginitis were identified, and 16 returned filled
      questionnaires. Study cohort consisted mainly of married, insured white women
      with more than 12 years of formal education and average or above average
      socioeconomic status. Median fluconazole MIC was 8 micrograms/mL (range 2-128
      micrograms/mL). Risk factors for mycologic failure included increased fluconazole
      consumption (P=.03) with 16 of 25 women exposed to low-dose weekly fluconazole
      maintenance therapy. All patients were clinically controlled successfully,
      although treatment was difficult and often prolonged. CONCLUSION: Fluconazole
      resistant C albicans vaginitis was previously considered rare. We report 25 cases
      over an 11-year period, indicating an emerging problem. All patients had
      fluconazole consumption in the previous 6 months. Management of fluconazole
      refractory disease is extremely difficult with limited options, and new
      therapeutic modalities are needed.

PMID- 23168768
TI  - Women in leadership positions within obstetrics and gynecology: does the past
      explain the present?
AB  - OBJECTIVE: To determine whether the proportion of leadership positions in
      obstetrics and gynecology held by women is consistent with expectations based on
      the proportion of women entering residency at the time of current leaders.
      METHODS: Leadership positions were considered as department chairs affiliated
      with the Council of University Chairs of Obstetrics and Gynecology, editors of
      the 20 obstetrics and gynecology journals with the highest impact factors
      [corrected],and presidents of influential professional societies. Publically
      available data were accessed to determine sex and the year of medical school
      graduation for each individual holding each leadership position, as well as to
      determine the number of men and women entering residency in obstetrics and
      gynecology per year. Actual and expected proportions of leadership positions held
      by women were compared using chi2 tests. RESULTS: Women should hold 71 of the
      total 194 leadership positions based on the proportion of women entering
      residency during the mean graduation year among leaders. Women actually hold 41
      of these leadership positions (21.1%; P<.001). Considering only leaders who
      graduated during the years in which residency matching data were available, women
      should hold 28 of these 74 leadership positions. Women actually hold 20 of the
      leadership positions from this subset (27.0%; P=.05). CONCLUSION: Women are
      underrepresented in leadership positions in obstetrics and gynecology, and this
      cannot be explained by historical sex imbalances among physicians entering our
      specialty.

PMID- 23168769
TI  - Factors predictive of postoperative morbidity and cost in patients with
      endometrial cancer.
AB  - OBJECTIVE: To identify patient characteristics and perioperative factors
      predictive of 30-day morbidity and cost in patients with endometrial carcinoma.
      METHODS: Data of consecutive patients treated with hysterectomy for endometrial
      carcinoma between 1999 and 2008 were collected prospectively. Thirty predictors
      were chosen from more than 130 collected based on anticipated clinical relevance
      and prevalence (more than 3%). Complications were graded per the Accordion
      Classification. Multivariable models were developed using stepwise and backward
      variable selection methods. Thirty-day cost analyses were expressed in 2010
      Medicare dollars. RESULTS: Of 1,369 patients, significant predictors (P<.01) of
      grade 2 and higher morbidity included American Society of Anesthesiologists
      physical status classification system class higher than 2 (odds ratio [OR] 2.1),
      preoperative white blood count (OR 2.1 per doubling), history of deep vein
      thrombosis (OR 2.1), pelvic and para-aortic lymphadenectomy (OR 2.3 compared with
      no lymphadenectomy), laparotomy (OR 2.8 compared with minimally invasive
      surgery), myometrial invasion more than 50% (OR 2.4), operating time (OR 1.9 per
      doubling), and grade 4 surgical complexity (OR 2.7 compared with grade 1). After
      controlling for patient factors in a multivariable model, laparotomy, pelvic, and
      para-aortic lymphadenectomy were associated with significant increases in cost
      compared with the use of minimally invasive surgery or hysterectomy alone.
      CONCLUSION: This analysis identifies patient and perioperative care factors
      predictive of 30-day morbidity and cost. These data are useful for preoperative
      counseling, for defining equitable reimbursement and factors critical for risk
      adjustment when comparing outcomes, and for identifying areas for quality
      improvement in patients with endometrial carcinoma. Given the marked increases in
      morbidity and cost associated with laparotomy and lymphadenectomy, minimally
      invasive surgery and selective lymphadenectomy should be standard treatment for
      patients with endometrial carcinoma.

PMID- 23168770
TI  - Postpartum Rh immunoprophylaxis.
AB  - The postpartum dose of Rh immune globulin varies according to an individual
      laboratory estimation of fetal red blood cells in each mother's peripheral blood.
      In the United States, a four-step procedure determines the postpartum dose
      (number of vials of 300 micrograms; 1,500 international units) of Rh immune
      globulin (anti-D) for each RhD-negative mother who has delivered an RhD-positive
      newborn and has not already formed anti-D. The first step is a rosette fetal red
      blood cell screen to determine whether an excessive (greater than 30 mL fetal
      whole blood) fetomaternal hemorrhage occurred. If the rosette screen is negative,
      the mother receives one vial of Rh immune globulin for Rh immunoprophylaxis. If
      the rosette screen is positive, the blood sample is retested by a quantitative
      method, typically an acid-elution (Kleihauer-Betke) assay. The result of the acid
      elution assay is converted to an estimation of the volume of the fetomaternal
      hemorrhage, which is the basis for calculating the dose of Rh immune globulin.
      The acid-elution assay is subjective, imprecise, and poorly reproducible. As a
      result, the formula for calculating the dose includes a precautionary adjustment,
      adding an extra vial in borderline situations to prevent underdosing. Flow
      cytometry is a more precise method for quantifying a fetomaternal hemorrhage.
      However, few hospitals use flow cytometry, because it is not cost-effective to
      maintain an expensive, high-technology laboratory service for the relatively few
      occasions when a precise quantitative determination of fetomaternal hemorrhage is
      required.

PMID- 23168771
TI  - Anthrax cases in pregnant and postpartum women: a systematic review.
AB  - OBJECTIVE: To describe the worldwide experience of Bacillus anthracis infection
      reported in pregnant, postpartum, and lactating women. DATA SOURCES: Studies were
      identified through MEDLINE, Web of Science, Embase, and Global Health databases
      from inception until May 2012. The key words (["anthrax" or "anthracis"] and
      ["pregna*" or "matern*" or "postpartum" or "puerperal" or "lact*" or "breastfed*"
      or "breastfeed*" or "fetal" or "fetus" or "neonate" or "newborn" or "abort*" or
      "uterus"]) were used. Additionally, all references from selected articles were
      reviewed, hand searches were conducted, and relevant authors were contacted.
      METHODS OF STUDY SELECTION: The inclusion criteria were: published articles
      referring to women diagnosed with an infection due to exposure to B anthracis
      during pregnancy, the postpartum period, or during lactation; any article type
      reporting patient-specific data; articles in any language; and nonduplicate
      cases. Non-English articles were professionally translated. Duplicate reports,
      unpublished reports, and review articles depicting previously identified cases
      were excluded. TABULATION, INTEGRATION, AND RESULTS: Two authors independently
      reviewed articles for inclusion. The primary search of the four databases yielded
      1,340 articles, and the secondary crossreference search revealed 146 articles.
      Fourteen articles met the inclusion criteria. In total, 20 cases of B anthracis
      infection were found, 17 in pregnant women, two in postpartum women, and one case
      in a lactating woman. Among these reports, 16 women died and 12 fetal or neonatal
      losses were reported. Of these fatal cases, most predated the advent of
      antibiotics. CONCLUSIONS: Based on these case reports, B anthracis infection in
      pregnant and postpartum women is associated with high rates of maternal and fetal
      death. Evidence of possible maternal-fetal transmission of B anthracis infection
      was identified in early case reports.

PMID- 23168772
TI  - Dexamethasone for antiemesis in laparoscopic gynecologic surgery: a systematic
      review and meta-analysis.
AB  - OBJECTIVE: To estimate the beneficial and harmful effects of dexamethasone for
      prevention of postoperative nausea and vomiting in women undergoing laparoscopic
      gynecologic surgery. DATA SOURCES: We searched the following bibliographic
      databases: MEDLINE (from 1946 to January 2012), Embase (from 1980 to 2012 week
      3), the Cochrane Central Register of Controlled Trials (from inception to January
      2012), and ISI Web of Knowledge (from 1950 to January 2012). We also screened
      trial registries, reference lists of retrieved studies, and other sources of
      unpublished literature. METHODS OF STUDY SELECTION: Two reviewers screened in
      duplicate and independently searched results for inclusion. We included
      randomized controlled trials (RCTs) comparing dexamethasone with a placebo in
      patients undergoing laparoscopic gynecologic surgery. TABULATION, INTEGRATION,
      AND RESULTS: Two reviewers completed data extraction and assessed trials for bias
      in duplicate and independently. We used the Grading of Recommendations
      Assessment, Development, and Evaluation methodology to assess the quality of
      evidence across studies at the outcome level. A total of 13 RCTs with 1,695
      patients met inclusion criteria. Data were pooled based on the random-effects
      model. The use of prophylactic dexamethasone significantly decreases the
      incidence of postoperative nausea (relative risk [RR] 0.56, 95% confidence
      interval [CI] 0.45-0.71), postoperative vomiting (RR 0.35, 95% CI 0.25-0.48), the
      need for rescue antiemetics (RR 0.39, 95% CI 0.29-0.52), and time to meet
      discharge criteria (mean 28.5 minutes, 95% CI 24.6-32.4). The estimated number
      needed to treat to prevent nausea in one patient was eight (95% CI 5-13), whereas
      that for vomiting was five (95% CI 4-6). There was no observed increase in
      adverse events. The quality of the evidence ranged from very low to moderate.
      CONCLUSION: This systematic review provides evidence that dexamethasone decreases
      the incidence of postoperative nausea and vomiting after laparoscopic gynecologic
      surgery, with no observed increase in side effects.

PMID- 23168773
TI  - Periurethral mass: a rare and puzzling entity.

PMID- 23168775
TI  - Stigma and abortion complications in the United States.
AB  - Abortion is highly stigmatized in the United States and elsewhere. As a result,
      many women who seek or undergo abortion keep their decision a secret. In many
      regions of the world, stigma is a recognized contributor to maternal morbidity
      and mortality from unsafe abortion, even when abortion is legal. Women may self
      induce abortion in ways that are dangerous, or seek unsafe clandestine abortion
      from inadequately trained health care providers out of fear that their sexual
      activity, pregnancy, or abortion will be exposed if they present to a safe,
      licensed facility. However, unsafe abortion rarely occurs in the United States,
      and accordingly, stigma as a cause of unsafe abortion in the United States
      context has not been described. I consider the relationship of stigma to two
      serious abortion complications experienced by U.S. patients. Both patients wished
      to keep their abortion decision a secret from family and friends, and in both
      cases, their inability to disclose their abortion contributed to life-threatening
      complications. The experiences of these patients suggest that availability of
      legal abortion services in the United States may not be enough to keep all women
      safe. The cases also challenge the rhetoric that "abortion hurts women,"
      suggesting instead that abortion stigma hurts women.

PMID- 23168774
TI  - Revised terminology for cervical histopathology and its implications for
      management of high-grade squamous intraepithelial lesions of the cervix.
AB  - In March 2012, the College of American Pathologists and American Society for
      Colposcopy and Cervical Pathology, in collaboration with 35 stakeholder
      organizations, convened a consensus conference called the Lower Anogenital
      Squamous Terminology (LAST) Project. The recommendations of this project include
      using a uniform, two-tiered terminology to describe the histology of human
      papillomavirus-associated squamous disease across all anogenital tract tissues:
      vulva, vagina, cervix, penis, perianus, and anus. The recommended terminology is
      "low-grade" or "high-grade squamous intraepithelial lesion (SIL)." This
      terminology is familiar to clinicians, because it parallels the terminology of
      the Bethesda System cytologic reports. Biopsy results using SIL terminology may
      be further qualified using "intraepithelial neoplasia" (IN) terminology in
      parentheses. Laboratory p16 tissue immunostaining is recommended to better
      classify histopathology lesions that morphologically would earlier have been
      diagnosed as IN 2. p16 is also recommended for differentiating between high-grade
      squamous intraepithelial lesions and benign mimics. The LAST Project
      recommendations potentially affect the application of current guidelines for
      managing cervical squamous intraepithelial lesions. The authors offer interim
      guidance for managing cervical lesions diagnosed using this new terminology with
      special attention paid to managing young women with cervical high-grade squamous
      intraepithelial lesions on biopsy. Clinicians should be aware of the LAST Project
      recommendations, which include important changes from prior terminology.

PMID- 23168776
TI  - Obstetrics and the Olympic spirit.

PMID- 23168777
TI  - What is new in contraception?: best articles from the past year.
AB  - This month, we focus on current research in contraception. Dr. Grimes discusses
      four recent publications, and each is concluded with a "bottom line" that is the
      take-home message. The complete reference for each can be found in  on this page,
      along with direct links to the abstracts.

PMID- 23168778
TI  - Mode of delivery and neonatal outcomes in preterm, small-for-gestational-age
      newborns.

PMID- 23168780
TI  - Practicing pelvic examinations by medical students on women under anesthesia: 
      why not ask first?

PMID- 23168781
TI  - Practicing pelvic examinations by medical students on women under anesthesia: 
      why not ask first?

PMID- 23168789
TI  - Practice Bulletin No. 132: Antiphospholipid syndrome.
AB  - Antiphospholipid syndrome (APS) is an autoimmune disorder defined by the presence
      of characteristic clinical features and specified levels of circulating
      antiphospholipid antibodies (Box 1 and Box 2). Diagnosis requires that at least
      one clinical and one laboratory criterion are met. Because approximately 70% of
      individuals with APS are female (1), it is reasonably prevalent among women of
      reproductive age. Antiphospholipid antibodies are a diverse group of antibodies
      with specificity for binding to negatively charged phospholipids on cell
      surfaces. Despite the prevalence and clinical significance of APS, there is
      controversy about the indications for and types of antiphospholipid tests that
      should be performed in order to diagnose the condition. Much of the debate
      results from a lack of well-designed and controlled studies on the diagnosis and
      management of APS. The purpose of this document is to evaluate the data for
      diagnosis and treatment of APS.

PMID- 23168790
TI  - Committee Opinion No.543: Timing of umbilical cord clamping after birth.
AB  - The optimal timing for clamping the umbilical cord after birth has been a subject
      of controversy and debate. Although many randomized controlled trials in term and
      preterm infants have evaluated the benefits of delayed umbilical cord clamping
      versus immediate umbilical cord clamping, the ideal timing for cord clamping has
      yet to be established. Several systematic reviews have suggested that clamping
      the umbilical cord in all births should be delayed for at least 30-60 seconds,
      with the infant maintained at or below the level of the placenta because of the
      associated neonatal benefits, including increased blood volume, reduced need for
      blood transfusion, decreased incidence of intracranial hemorrhage in preterm
      infants, and lower frequency of iron deficiency anemia in term infants. Evidence
      exists to support delayed umbilical cord clamping in preterm infants, when
      feasible. The single most important clinical benefit for preterm infants is the
      possibility for a nearly 50% reduction in intraventricular hemorrhage. However,
      currently, evidence is insufficient to confirm or refute the potential for
      benefits from delayed umbilical cord clamping in term infants, especially in
      settings with rich resources.

PMID- 23168791
TI  - Committee Opinion No 544: Over-the-counter access to oral contraceptives.
AB  - Unintended pregnancy remains a major public health problem in the United States.
      Access and cost issues are common reasons why women either do not use
      contraception or have gaps in use. A potential way to improve contraceptive
      access and use, and possibly decrease unintended pregnancy rates, is to allow
      over-the-counter access to oral contraceptives (OCs). Screening for cervical
      cancer or sexually transmitted infections is not medically required to provide
      hormonal contraception. Concerns include payment for pharmacist services, payment
      for over-the-counter OCs by insurers, and the possibility of pharmacists
      inappropriately refusing to provide OCs. Weighing the risks versus the benefits
      based on currently available data, OCs should be available over-the-counter.
      Women should self-screen for most contraindications to OCs using checklists.

PMID- 23168792
TI  - Committee Opinion No. 545: Noninvasive prenatal testing for fetal aneuploidy.
AB  - Noninvasive prenatal testing that uses cell free fetal DNA from the plasma of
      pregnant women offers tremendous potential as a screening tool for fetal
      aneuploidy. Cell free fetal DNA testing should be an informed patient choice
      after pretest counseling and should not be part of routine prenatal laboratory
      assessment. Cell free fetal DNA testing should not be offered to low-risk women
      or women with multiple gestations because it has not been sufficiently evaluated
      in these groups. A negative cell free fetal DNA test result does not ensure an
      unaffected pregnancy. A patient with a positive test result should be referred
      for genetic counseling and should be offered invasive prenatal diagnosis for
      confirmation of test results.

PMID- 23168793
TI  - Committee Opinion No.546: Tracking and reminder systems.
AB  - An accurate and effective tracking or reminder system is useful for the modern
      practice of obstetrics and gynecology. Practices should not rely solely on the
      patient to complete all ordered studies and to follow up on health care provider
      recommendations. Health care providers should encourage their patients to
      complete studies believed essential for patient care within an acceptable time
      frame. Each office should establish a simple, reliable tracking and reminder
      system to facilitate communication, improve patient safety and quality of care,
      and minimize missed or delayed diagnoses.

PMID- 23168794
TI  - Committee Opinion No. 547: Health care for women in the military and women
      veterans.
AB  - Military service is associated with unique risks to women's reproductive health.
      As increasing numbers of women are serving in the military, and a greater
      proportion of United States Veterans are women, it is essential that obstetrician
      gynecologists are aware of and well prepared to address the unique health care
      needs of this demographic group. Obstetrician-gynecologists should ask about
      women's military service, know the Veteran status of their patients, and be aware
      of high prevalence problems (eg, posttraumatic stress disorder, intimate partner
      violence, and military sexual trauma) that can threaten the health and well-being
      of these women. Additional research examining the effect of military and Veteran
      status on reproductive health is needed to guide the care for this population.
      Moreover, partnerships between academic departments of obstetrics and gynecology
      and local branches of the Veterans Health Administration are encouraged as a
      means of optimizing the provision of comprehensive health care to this unique
      group of women.

PMID- 23168795
TI  - FAK regulates Cdk2 in EGF-stimulated primary cultures of hepatocytes.
AB  - In this study, we report a novel role of FAK as a regulator of Cdk2 in anchorage
      dependent primary cultured hepatocytes. In response to EGF, we found that S-phase
      entry was reduced upon FAK inhibition. This correlated with decreased protein
      expression and nuclear accumulation of the G1/S-phase regulator Cdk2. Further,
      nuclear accumulation of the Cdk2 partner cyclinE, was reduced, but not its
      protein level. Also, protein levels of Cdk2 were inversely linked with increased
      expression of the Cdk2 inhibitor p27, known to be degraded in a Cdk2-dependent
      manner. Also, cyclinD1 was regulated by FAK, but to a lesser extent than Cdk2. To
      assess the mechanism in which FAK mediates Cdk2-regulation, FAK mutants were
      used: FAKY397F, mutated at its integrin-regulated site, and two others mutated at
      docking sites for Grb2-ERK-activation (FAKY925F) and for p130Cas-Rac1-activation
      (FAKY861F). All three sites were central for EGF-induced ERK-activity and Cdk2
      expression. In addition, FAK was important for HGF-mediated proliferation,
      suggesting a general mechanism for anchorage-dependent growth. Moreover, growth
      factor-induced cell spreading, but not survival, required FAK. Hence, integrins
      and growth factors cooperate in anchorage-dependent signaling events leading to
      proliferation and motility. In conclusion, our data suggest that FAK acts as a
      central coordinator of integrin and growth factor-mediated S-phase entry by its
      ability to regulate Cdk2.

PMID- 23168797
TI  - Protein misfolding cyclic amplification of prions.
AB  - Prions are infectious agents that cause the inevitably fatal transmissible
      spongiform encephalopathy (TSE) in animals and humans(9,18). The prion protein
      has two distinct isoforms, the non-infectious host-encoded protein (PrP(C)) and
      the infectious protein (PrP(Sc)), an abnormally-folded isoform of PrP(C 8). One
      of the challenges of working with prion agents is the long incubation period
      prior to the development of clinical signs following host inoculation(13). This
      traditionally mandated long and expensive animal bioassay studies. Furthermore,
      the biochemical and biophysical properties of PrP(Sc) are poorly characterized
      due to their unusual conformation and aggregation states. PrP(Sc) can seed the
      conversion of PrP(C) to PrP(Sc) in vitro(14). PMCA is an in vitro technique that
      takes advantage of this ability using sonication and incubation cycles to produce
      large amounts of PrP(Sc), at an accelerated rate, from a system containing excess
      amounts of PrP(C) and minute amounts of the PrP(Sc) seed(19). This technique has
      proven to effectively recapitulate the species and strain specificity of PrP(Sc)
      conversion from PrP(C), to emulate prion strain interference, and to amplify very
      low levels of PrP(Sc) from infected tissues, fluids, and environmental
      samples(6,7,16,23) . This paper details the PMCA protocol, including
      recommendations for minimizing contamination, generating consistent results, and
      quantifying those results. We also discuss several PMCA applications, including
      generation and characterization of infectious prion strains, prion strain
      interference, and the detection of prions in the environment.

PMID- 23168798
TI  - Evaluation of the bactericidal effect of Nd:YAG, Er:YAG, Er,Cr:YSGG laser
      radiation, and antimicrobial photodynamic therapy (aPDT) in experimentally
      infected root canals.
AB  - BACKGROUND AND OBJECTIVE: In recent years, various laser systems have been
      introduced into the field of laser-assisted endodontic therapy. The aim of this
      study was to evaluate the bactericidal effect of Nd:YAG, Er:YAG, Er,Cr:YSGG laser
      radiation, and antimicrobial photodynamic therapy (aPDT) in experimentally
      infected root canals compared with standard endodontic treatment of 5.25% sodium
      hypochlorite (NaClO) irrigation. MATERIALS AND METHODS: Two hundred and twenty
      infected root canals from extracted human teeth (contaminated with Enterococcus
      faecalis ATCC 4083 for 4 weeks) were randomly divided into five experimental
      groups (Nd:YAG, Er:YAG + 5.25% NaClO + 0.9% normal saline + distilled water
      (Er:YAG/NaClO/NS/DW), Er:YAG + 0.9% normal saline + distilled water
      (Er:YAG/NS/DW), Er,Cr:YSGG, and aPDT) and two control groups (5.25% NaClO as
      positive control and 0.9% normal saline (NS) as negative control). The numbers of
      bacteria on the surface of root canal walls and at different depths inside
      dentinal tubules before and after treatment were analyzed by means of one-way
      analysis of variance (one-way ANOVA). The morphology of bacterial cells before
      and after treatment was examined by scanning electron microscopy (SEM). RESULTS:
      After treatment, the bacterial reductions in the experimental groups and the
      positive control group were significantly greater than that of the negative
      control group (P < 0.001). However, only Er:YAG/NaClO/NS/DW group showed no
      bacterial growth (the bacterial reduction reached up to 100%) on the surface of
      root canal walls or at 100/200 um inside the dentinal tubules. CONCLUSIONS: All
      the laser radiation protocols tested, especially Er:YAG/NaClO/NS/DW, have
      effective bactericidal effect in experimentally infected root canals.
      Er:YAG/NaClO/NS/DW seems to be an ideal protocol for root canal disinfection
      during endodontic therapy.

PMID- 23168799
TI  - Expression changes of cytoskeletal associated proteins in proteomic profiling of
      neuroblastoma cells infected with different strains of rabies virus.
AB  - Rabies virus invades the nervous system, induces neuronal dysfunction and causes
      death of the host. The disruption of the cytoskeletal integrity and synaptic
      structures of the neurons by rabies virus has been postulated as a possible basis
      for neuronal dysfunction. In the present study, a two-dimensional
      electrophoresis/mass spectrometry proteomics analysis of neuroblastoma cells
      revealed a significant effect of a virulent strain of rabies virus on the host
      cytoskeleton related proteins which was quite different from that of an
      attenuated strain. Vimentin, actin cytoplasmic 1 isoform, profilin I, and Rho-GDP
      dissociation inhibitor were host cell cytoskeletal related proteins changed by
      the virulent strain. The proteomics data indicated that the virulent strain of
      rabies virus induces significant expression changes in the vimentin and actin
      cytoskeleton networks of neurons which could be a strong clue for the relation of
      cytoskeletal integrity distraction and rabies virus pathogenesis. In addition,
      the expression alteration of other host proteins, particularly some structural
      and regulatory proteins may have potential roles in rabies virus pathogenesis.

PMID- 23168802
TI  - The cover. Snow and water.

PMID- 23168805
TI  - Scientists confront joint HIV-TB epidemics by taking fight to the front lines.
      Interview by Bridget M. Kuehn.

PMID- 23168806
TI  - ACIP: Give pertussis vaccine during every pregnancy.

PMID- 23168807
TI  - Sequencing inches closer to the clinic: neonatal, intellectual disorders
      identified.

PMID- 23168814
TI  - Cardiovascular disease risk prediction factors.

PMID- 23168815
TI  - Cardiovascular disease risk prediction factors.

PMID- 23168817
TI  - Interferon-gamma-release assays for latent tuberculosis.

PMID- 23168819
TI  - Association between positive age stereotypes and recovery from disability in
      older persons.

PMID- 23168821
TI  - Mentoring translational science investigators.

PMID- 23168822
TI  - A piece of my mind. No more apologies.

PMID- 23168824
TI  - Association of online patient access to clinicians and medical records with use
      of clinical services.
AB  - CONTEXT: Prior studies suggest that providing patients with online access to
      health records and e-mail communication with physicians may substitute for
      traditional health care services. OBJECTIVE: To assess health care utilization by
      both users and nonusers of online access to health records before and after
      initiation of MyHealthManager (MHM), a patient online access system. DESIGN,
      SETTING, AND PARTICIPANTS: Retrospective cohort study of the use of health care
      services by members (>=18 years old) who were continuously enrolled for at least
      24 months during the study period March 2005 through June 2010 in Kaiser
      Permanente Colorado, a group model, integrated health care delivery system.
      Propensity scores (using age, sex, utilization frequencies, and chronic
      illnesses) were used for cohort matching. Unadjusted utilization rates were
      calculated for both MHM users and nonusers and were the basis for difference-of
      differences analyses. We also used generalized estimating equations to compare
      the adjusted rates of utilization of health care services before and after online
      access. MAIN OUTCOME MEASURES: Rates of office visits, telephone encounters,
      after-hours clinic visits, emergency department encounters, and hospitalizations
      between members with and without online access. RESULTS: Comparing the unadjusted
      rates for use of clinical services before and after the index date between the
      matched cohorts, there was a significant increase in the per-member rates of
      office visits (0.7 per member per year; 95% CI, 0.6-0.7; P < .001) and telephone
      encounters (0.3 per member per year; 95% CI, 0.2-0.3; P < .001). There was also a
      significant increase in per-1000-member rates of after-hours clinic visits (18.7
      per 1000 members per year; 95% CI, 12.8-24.3; P < .001), emergency department
      encounters (11.2 per 1000 members per year; 95% CI, 2.6-19.7; P = .01), and
      hospitalizations (19.9 per 1000 members per year; 95% CI, 14.6-25.3; P < .001)
      for MHM users vs nonusers. CONCLUSION: Having online access to medical records
      and clinicians was associated with increased use of clinical services compared
      with group members who did not have online access.

PMID- 23168823
TI  - Effect of citicoline on functional and cognitive status among patients with
      traumatic brain injury: Citicoline Brain Injury Treatment Trial (COBRIT).
AB  - CONTEXT: Traumatic brain injury (TBI) is a serious public health problem in the
      United States, yet no treatment is currently available to improve outcome after
      TBI. Approved for use in TBI in 59 countries, citicoline is an endogenous
      substance offering potential neuroprotective properties as well as facilitated
      neurorepair post injury. OBJECTIVE: To determine the ability of citicoline to
      positively affect functional and cognitive status in persons with complicated
      mild, moderate, and severe TBI. DESIGN, SETTING, AND PATIENTS: The Citicoline
      Brain Injury Treatment Trial (COBRIT), a phase 3, double-blind randomized
      clinical trial conducted between July 20, 2007, and February 4, 2011, among 1213
      patients at 8 US level 1 trauma centers to investigate effects of citicoline vs
      placebo in patients with TBI classified as complicated mild, moderate, or severe.
      INTERVENTION: Ninety-day regimen of daily enteral or oral citicoline (2000 mg) or
      placebo. MAIN OUTCOME MEASURES: Functional and cognitive status, assessed at 90
      days using the TBI-Clinical Trials Network Core Battery. A global statistical
      test was used to analyze the 9 scales of the core battery. Secondary outcomes
      were functional and cognitive improvement, assessed at 30, 90, and 180 days, and
      examination of the long-term maintenance of treatment effects. RESULTS: Rates of
      favorable improvement for the Glasgow Outcome Scale-Extended were 35.4% in the
      citicoline group and 35.6% in the placebo group. For all other scales the rate of
      improvement ranged from 37.3% to 86.5% in the citicoline group and from 42.7% to
      84.0% in the placebo group. The citicoline and placebo groups did not differ
      significantly at the 90-day evaluation (global odds ratio [OR], 0.98 [95% CI,
      0.83-1.15]); in addition, there was no significant treatment effect in the 2
      severity subgroups (global OR, 1.14 [95% CI, 0.88-1.49] and 0.89 [95% CI, 0.72
      1.49] for moderate/severe and complicated mild TBI, respectively). At the 180-day
      evaluation, the citicoline and placebo groups did not differ significantly with
      respect to the primary outcome (global OR, 0.87 [95% CI, 0.72-1.04]). CONCLUSION:
      Among patients with traumatic brain injury, the use of citicoline compared with
      placebo for 90 days did not result in improvement in functional and cognitive
      status. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00545662.

PMID- 23168826
TI  - The changing landscape of ICU sedation.

PMID- 23168825
TI  - Nonpharmacologic management of behavioral symptoms in dementia.
AB  - Behavioral symptoms such as repetitive speech, wandering, and sleep disturbances
      are a core clinical feature of Alzheimer disease and related dementias. If
      untreated, these behaviors can accelerate disease progression, worsen functional
      decline and quality of life, cause significant caregiver distress, and result in
      earlier nursing home placement. Systematic screening for behavioral symptoms in
      dementia is an important prevention strategy that facilitates early treatment of
      behavioral symptoms by identifying underlying causes and tailoring a treatment
      plan. First-line nonpharmacologic treatments are recommended because available
      pharmacologic treatments are only modestly effective, have notable risks, and do
      not effectively treat some of the behaviors that family members and caregivers
      find most distressing. Examples of nonpharmacologic treatments include provision
      of caregiver education and support, training in problem solving, and targeted
      therapy directed at the underlying causes for specific behaviors (eg,
      implementing nighttime routines to address sleep disturbances). Based on an
      actual case, we characterize common behavioral symptoms and describe a strategy
      for selecting evidence-based nonpharmacologic dementia treatments.
      Nonpharmacologic management of behavioral symptoms in dementia can significantly
      improve quality of life and patient-caregiver satisfaction.

PMID- 23168827
TI  - Effective treatment of traumatic brain injury: learning from experience.

PMID- 23168828
TI  - Personal health records and health care utilization.

PMID- 23168833
TI  - JAMA patient page. Steroid injections to treat back pain.

PMID- 23168834
TI  - Highly stereoselective, cobalt(III)-directed Mannich additions in water yielding
      alpha-methylamino acid products.
AB  - Highly stereoselective and rapid (<1 min) addition reactions to the imine double
      bond of 2-(methylimino)acetate complexes [L(4)Co(O(2)CCH=NCH(3))](2+) [L(4) =
      (en)(2) (7), (tren) (11)] were achieved in aqueous solution with nitromethane,
      ethyl 3-oxobutanoate or diethyl malonate. The molecular structures of two product
      complexes, rac-(Delta*-R(C)*-S(N)*)
      [Co(en)(2)(O(2)CCH[CH(2)NO(2)]NHCH(3))]ZnCl(4) and rac-(Delta*-R(C)*-S(N)*)
      [Co(en)(2)(O(2)CCH[CH(2)COCH(3)]NHCH(3))]ZnCl(4), were established by X-ray
      diffraction.

PMID- 23168835
TI  - Evaluation of small bowel bleeding.
AB  - PURPOSE OF REVIEW: The review focuses on the latest techniques that are evolving
      in the management of small bowel bleeding. RECENT FINDINGS: Video capsule
      endoscopy has the highest yield of diagnosis when it is performed within 48 h of
      the bleeding event (78 versus 48%). The pooled detection rate of double balloon
      endoscopy was noted to be 68.1% for obscure gastrointestinal bleeding according
      to a systematic review of 66 studies in the last 10 years. Also a recent review,
      which focused on analysis of 68 studies found that the procedural characteristics
      were comparable for double balloon, single balloon and spiral enteroscopy though
      the procedure time was fastest for the spiral enteroscopy group. Medical therapy
      for vascular lesions is in its infancy but shows promise. SUMMARY: Advanced
      diagnostic and therapeutic endoscopic techniques are changing the paradigm of
      care for patients with small bowel bleeding.

PMID- 23168836
TI  - Endogenous IL-21 regulates pathogenic mucosal CD4 T-cell responses during
      enhanced RSV disease in mice.
AB  - A role for interleukin-21 (IL-21) has recently been found in several diseases,
      but contribution to mucosal defences has not been described. In BALB/c mice
      infected with respiratory syncytial virus (RSV), IL-21 depletion had little
      effect in primary infection. However, depletion of mice during priming with
      recombinant vaccinia expressing RSV G protein (which primes RSV-specific T helper
      type 2 cells and causes lung eosinophilia during RSV infection) further
      exacerbated pathology during RSV challenge, with reduced viral clearance and
      impaired virus-specific serum antibody responses. This enhancement was
      accompanied by lymphocyte, neutrophil, and antigen-presenting cell recruitment to
      the lungs, with increased bronchoalveolar lavage interferon-gamma and IL-17
      levels. Adoptive transfer of splenic CD4 T cells from depleted mice into naive
      recipients replicated these effects, indicating that IL-21 mediates its effects
      via CD4 T cells. Endogenous IL-21, therefore, has potent and specific effects on
      mucosal antiviral responses, assisting viral clearance, regulating pulmonary T-
      and B-cell responses, and inhibiting IL-17 production.

PMID- 23168837
TI  - Migratory properties of pulmonary dendritic cells are determined by their
      developmental lineage.
AB  - The chemokine receptor, CCR7, directs the migration of dendritic cells (DCs) from
      peripheral tissue to draining lymph nodes (LNs). However, it is unknown whether
      all pulmonary DCs possess migratory potential. Using novel Ccr7(gfp) reporter
      mice, we found that Ccr7 is expressed in CD103+ and a CD14(med/lo) subset of
      CD11b(hi) classical (c)DCs but not in monocyte-derived (mo)DCs, including Ly
      6C(hi)CD11b(hi) inflammatory DCs and CD14(hi)CD11b(hi) DCs. Consequently, cDCs
      migrated to lung-draining LNs but moDCs did not. Mice lacking the chemokine
      receptor, CCR2, also lacked inflammatory DCs in the lung after lipopolysaccharide
      inhalation but retained normal levels of migratory DCs. Conversely, the lungs of
      fms-like tyrosine kinase 3 ligand (Flt3L)-deficient mice lacked cDCs but retained
      moDCs, which were functionally mature but did not express Ccr7 and were uniformly
      non-migratory. Thus, the migratory properties of pulmonary DCs are determined by
      their developmental lineage.

PMID- 23168838
TI  - A mechanistic role for leptin in human dendritic cell migration: differences
      between ileum and colon in health and Crohn's disease.
AB  - Dendritic cells (DC) migrate to lymph nodes on expression of C-C motif chemokine
      receptor 7 (CCR7) and control immune activity. Leptin, an immunomodulatory
      adipokine, functions via leptin receptors, signaling via the long isoform of
      receptor, LepRb. Leptin promotes DC maturation and increases CCR7 expression on
      blood DC. Increased mesenteric fat and leptin occur early in Crohn's disease
      (CD), suggesting leptin-mediated change in intestinal CCR7 expression on DC as a
      pro-inflammatory mechanism. We have demonstrated CCR7 expression and capacity to
      migrate to its ligand macrophage inflammatory protein 3beta in normal human ileal
      DC but not colonic or blood DC. In CD, functional CCR7 was expressed on DC from
      all sites. Only DC populations containing CCR7-expressing cells produced LepRb;
      in vitro exposure to leptin also increased expression of functional CCR7 in
      intestinal DC in a dose-dependent manner. In conclusion, leptin may regulate DC
      migration from gut, in homeostatic and inflammatory conditions, providing a link
      between mesenteric obesity and inflammation.

PMID- 23168840
TI  - Physical therapy management of female chronic pelvic pain: Anatomic
      considerations.
AB  - The multisystem nature of female chronic pelvic pain (CPP) makes this condition a
      challenge for physical therapists and other health care providers to manage. This
      article uses a case scenario to illustrate commonly reported somatic, visceral,
      and neurologic symptoms and their associated health and participation impact in a
      female with CPP. Differential diagnosis of pain generators requires an in-depth
      understanding of possible anatomic and physiologic contributors to this disorder.
      This article provides a detailed discussion of the relevant clinical anatomy with
      specific attention to complex interrelationships between anatomic structures
      potentially leading to the patient's pain. In addition, it describes the physical
      therapy management specific to this case, including examination, differential
      diagnosis, and progression of interventions.

PMID- 23168839
TI  - The ER stress transducer IRE1beta is required for airway epithelial mucin
      production.
AB  - Inflammation of human bronchial epithelia (HBE) activates the endoplasmic
      reticulum (ER) stress transducer inositol-requiring enzyme 1 (IRE1)alpha,
      resulting in IRE1alpha-mediated cytokine production. Previous studies
      demonstrated ubiquitous expression of IRE1alpha and gut-restricted expression of
      IRE1beta. We found that IRE1beta is also expressed in HBE, is absent in human
      alveolar cells, and is upregulated in cystic fibrosis and asthmatic HBE. Studies
      with Ire1beta(-/-) mice and Calu-3 airway epithelia exhibiting IRE1beta knockdown
      or overexpression revealed that IRE1beta is expressed in airway mucous cells, is
      functionally required for airway mucin production, and this function is specific
      for IRE1beta vs. IRE1alpha. IRE1beta-dependent mucin production is mediated, at
      least in part, by activation of the transcription factor X-box binding protein-1
      (XBP-1) and the resulting XBP-1-dependent transcription of anterior gradient
      homolog 2, a gene implicated in airway and intestinal epithelial mucin
      production. These novel findings suggest that IRE1beta is a potential mucous cell
      specific therapeutic target for airway diseases characterized by mucin
      overproduction.

PMID- 23168841
TI  - One-pot hydrothermal synthesis of lanthanide ions doped one-dimensional
      upconversion submicrocrystals and their potential application in vivo CT imaging.
AB  - Multi-functional rare-earth Yb(3+) and Ln(3+) (Ln = Er, Tm and Ho) ions doped one
      dimensional (1-D) upconversion submicrocrystals (NaYF(4) and NaGdF(4)) possessing
      upconversion luminescence, biocompatibility and magnetic properties have been
      synthesized by a one-pot hydrothermal method. Rare-earth Yb(3+) and Ln(3+) ions
      doped NaYF(4) microrods (~1 MUm in diameter, 3-5 MUm in length) exhibit porous
      properties, and the average pore sizes are ~28.2 nm. They show paramagnetism in
      the magnetic range of -60 to -2 kOe and 2 to 60 kOe at 300 K, and exhibit near
      superparamagnetic behaviour at the magnetic range of -2 to 2 kOe. Saturation
      magnetization was ~12.1 emu g(-1) at 2 K. The Yb(3+) and Ln(3+) ions doped
      NaGdF(4) submicrocrystals (~100 nm in diameter, 200-300 nm in length) show
      paramagnetism at 300 K, and exhibit superparamagnetic behaviour with a saturation
      magnetization of 129.2 emu g(-1) at 2 K. The magnetic properties of Yb(3+) and
      Ln(3+) ions doped 1-D upconversion submicrocrystals indicate they can be used for
      drug targeting under a magnetic field. Their unique upconversion emission (green
      for Yb(3+)/Er(3+) and blue for Yb(3+)/Tm(3+)) under 980 nm laser excitation
      indicate that they could be used for specific luminescent immunolabeling and
      imaging. MTT assays reveal that 1-D upconversion submicrocrystals have
      satisfactory bio-affinity, where the viability keeps in good state even at a
      concentration of 500 MUg mL(-1), which is much higher than the concentration
      usually used in cell labelling. Luminescent microscopy images show that the
      morphologies of the cytoskeleton and cell nucleus are well maintained after
      incubating different concentrations of 1-D upconversion submicrocrystals. After
      injecting upconversion submicrocrystals into the mice (tumor sites or back normal
      tissue), a clearly distinguished CT signal was observed, indicating the
      synthesized 1-D submicrocrystals are effective for CT imaging in vivo.

PMID- 23168842
TI  - Modalities of hemodialysis: quality improvement.
AB  - Hemodialysis (HD) treatment had, over many years, improved the survival rate of
      patients with end-stage renal disease. However, standard or conventional HD
      prescription is far from being optimal in replacing the function of normal
      kidneys. Its unphysiologic clearance pattern and inability to remove all types
      and sizes of uremic toxins results in inter- and intra-dialysis complications and
      an unacceptably high rate of cardiovascular morbidity and mortality. Efficiency
      of HD can be improved by increasing blood and dialysate flow rates, dialyzer size
      and surface area and duration and frequency of dialysis sessions. Home HD, where
      short daily or long slow nocturnal HD sessions can conveniently be performed,
      provides an excellent option for quality of life improvement and reduction in
      morbidity and mortality. Recent innovations in the specifications of HD machines
      and improvement in dialysis membranes characteristics and water treatment
      technology paved the way for achieving quality HD. These advancements have
      resulted in efficient implementation of adsorption, diffusion and/or convection
      principles using adsorption HD, hemofiltration, hemodiafiltration (HDF) and
      online HDF modalities in order to achieve optimum HD. Implementation of these
      innovations resulted in better quality care achievements in clinical practice and
      reduction in morbidity and mortality rates among HD patients.

PMID- 23168843
TI  - Symptomatic lymphocoeles post renal transplant.
AB  - The aim of this study was to evaluate the outcome of various treatment modalities
      of symptomatic lymphoceles and suggest an optimal management protocol. Case
      records of 744 renal transplant recipients who underwent surgery between January
      2000 and December 2007 were retrospectively reviewed. There were a total of 36
      (4.38%) lymphoceles detected in the postoperative period, of which 14 (1.88%)
      were symptomatic. A total of 32 procedures for the treatment of lymphocele were
      performed in 14 of these patients. Aspiration or percutaneous catheter drainage
      was performed as a primary procedure in all cases. Open marsupialization and
      laparoscopic marsupialization procedures were performed as secondary treatments.
      Percutaneous nephrostomy was required in one case before definitive treatment.
      Primary aspiration was successful in (n = 2) 28.5% and percutaneous drainage in
      (n = 3) 42.8%. Sclerotherapy was definitive in (n = 2 of 3) 66.6%. Seven of 14
      patients required secondary procedure. Laparoscopic marsupialization was
      successful in (n = 4 of 5) 80% and open technique (n = 3) was curative in all
      cases. In our opinion, the first step in the management of symptomatic lymphocele
      in post-renal transplant recipients should be percutaneous drainage with or
      without drug instillation. This can stabilize renal function and optimize
      patients who may require surgery. Surgical marsupialization offers superior
      definitive treatment of lymphoceles with the least recurrence rates.

PMID- 23168844
TI  - Graft function based on two hours peak level monitoring of cyclosporine A during
      the first six months of renal transplantation.
AB  - Inadequate cyclosporine blood levels may cause acute rejection in transplanted
      renal graft, and its increase is accompanied with graft toxicity. Cyclosporine
      has variable bioavailability and pharmacokinetics among patients at different
      times after transplantation. In this study, we compared the effects of
      cyclosporine blood levels (trough versus 2-hour peak, C2) on renal graft function
      during the first six months after transplantation in order to find better methods
      for drug levels assessment in our patients. We studied 50 patients who received
      grafts at Mashhad transplant centers from October 2006 to May 2007. Drug levels
      were monitored seven times during the study; in each assessment, more than 80% of
      the patients did not reach the therapeutic C2 levels. There was no significant
      correlation between age, sex, times of transplantation and acute rejection with
      drug C2 levels. There was no difference between graft function in patients with
      therapeutic C2 level and those with inadequate C2 levels. However, we found a
      significant correlation between trough levels and acute rejection (P <0.05). Only
      during the 6 th month after transplantation was the drug dosage significantly
      higher in patients with therapeutic C2 level than that in other patients (P
      >0.05). Apparently, peak levels were not a suitable method in drug monitoring in
      our patients, or peak levels might have occurred at a different time (like 1.5 or
      3 or 4 h after ingestion of the drug) in our population. Based on this study,
      trough level may be a better method of evaluation of cyclosporine effects on
      renal allografts than 2-h peak levels in our patients.

PMID- 23168845
TI  - Laparoscopic donor nephrectomy versus open donor nephrectomy: recipient's
      perspective.
AB  - Effects of laparoscopic donor nephrectomy (LDN) on graft function, especially
      early post-transplant, have been controversial. To assess and compare early and
      late graft function in kidneys procured by open and laparoscopic methods, a
      retrospective observational study was carried out on 37 recipients-donors who
      underwent LDN after introduction of this technique in February 2007 at our
      center, a tertiary care nephrology referral center. Demographic, immunological
      and intraoperative variables as well as immunosuppressive protocols and number of
      human leukocyte antigen (HLA) mismatches were noted. Early graft function was
      assessed by serum creatinine on Days two, five, seven, 14 and 28 and at the time
      of discharge. Serum creatinine values at three months and at one year post
      transplant were considered as the surrogates of late graft function. Data
      obtained were compared with the data from 33 randomly selected kidney transplants
      performed after January 2000 by the same surgical team, in whom open donor
      nephrectomy was used. Pearson's chi square test, Student's t test and Mann
      Whitney U test were used for statistical analysis. Early graft function (serum
      creatinine on Day five 2.15 mg/dL vs 1.49 mg/dL, P = 0.027) was poorer in the LDN
      group. Late graft function as assessed by serum creatinine at three months (1.45
      mg/dL vs 1.31 mg/dL, P = 0.335) and one year (1.56 mg/dL vs 1.34 mg/dL, P =
      0.275) was equivalent in the two groups. Episodes of early acute graft
      dysfunction due to acute tubular necrosis were significantly higher in the LDN
      group (37.8% vs 12.1%, Z score 2.457, P = 0.014). Warm ischemia time was
      significantly prolonged in the LDN group (255 s vs 132.5 s, P = 0.002). LDN is
      associated with slower recovery of graft function and higher incidence of early
      acute graft dysfunction due to acute tubular necrosis. Late graft function at one
      year is however comparable.

PMID- 23168846
TI  - Extended open-carpal tunnel release in renal dialysis patients.
AB  - Chronic hemodialysis patients are susceptible to median nerve compression. The
      clinical symptoms, surgical results and prognosis of chronic hemodialysis-related
      carpal tunnel syndrome have different results from those of idiopathic carpal
      tunnel syndrome. The aim of this study was to evaluate the clinical results of
      extended open carpal tunnel release in chronic hemodialysis-related carpal tunnel
      syndrome. A review of 31 open-extended carpal tunnel decompressions in 27 chronic
      dialysis patients was performed. The surgical technique is detailed and the
      clinical results analyzed. There was an improvement in symptoms and strength in
      all patients. There were no instances of recurrence of nerve compression during
      the one year follow-up period. Extended open carpal tunnel decompression improves
      symptoms and enhances hand function in patients receiving chronic hemodialysis.

PMID- 23168848
TI  - Morphometry of non-inflammatory arteriolar changes in lupus nephritis: a study of
      40 cases.
AB  - Vascular changes in lupus nephritis (LN) may be the cause of renal function
      derangement without obvious changes in activity or chronicity indices. Although a
      few morphological studies of renal vasculature exist, arteriolar morphometric
      parameters in LN have not been evaluated. For this study, 40 patients with LN and
      40 age-matched patients with minimal change disease (controls) were included.
      Their clinical features were noted, renal biopsy changes classified according to
      the modified World Health Organization classification of LN and activity and
      chronicity indices were calculated. Arteriolar morphometric parameters were
      obtained using manual tracing and an image analysis software. Appropriate
      statistical tests were applied to assess significance of difference between
      various groups. Arteriolar wall thickness as well as circumference was
      significantly higher in all classes of LN as compared with controls (P <0.05).
      However, no difference was observed in the wall-to-lumen ratio between the two
      groups (P >0.05). An inter-class analysis of LN did not show any significant
      difference for any of the arteriolar morphometric parameters (P >0.05). No
      correlation was found between activity or chronicity indices and the various
      arteriolar morphometric parameters. This study demonstrates morphometric evidence
      of arteriolar wall changes in LN. Although no correlation was found with the
      histological features, further studies are required in this area.

PMID- 23168847
TI  - Relationship between serum parathyroid hormone levels and lipid profile in non
      diabetic hemodialysis patients.
AB  - Elevated levels of intact parathyroid hormone (iPTH) may play an important role
      in the pathogenesis of the dyslipidemia in hemodialysis (HD) patients, but the
      underlying mechanisms are not clearly defined. In this cross-sectional study, we
      examined the effects of iPTH on dyslipidemia among HD patients by analyzing the
      data of 51 patients (18 males and 33 females) with combined mean age 51.7 +/-
      18.3 years (range 22-85 years) who were on HD between April 2009 and April 2010,
      in the dialysis center of Imam Khomeini Hospital Complex in Iran. On enrollment,
      we measured lipid profile, apoprotein (apo) A, apo B, alkaline phosphatase,
      calcium and phosphorus and also recorded the duration that they were on HD, and
      evaluated the correlation of these with iPTH level using Spearman's rank
      analysis. The mean duration on HD was 7.07 +/- 6.53 years. Except for high
      density lipoprotein, there were no changes in the lipid parameters in our HD
      patients. We also compared lipid profile among subjects, classifying them
      according to their iPTH levels. There was no correlation between serum lipids and
      iPTH levels in these groups. A significant positive correlation was found between
      iPTH and alkaline phosphatase( ALP) (r = 0.333, P = 0.017) between iPTH and HD
      duration (r = 0.408, P = 0.003), whereas there was a significant negative
      correlation between iPTH and Ca (r = -0.294, P = 0.037) between iPTH and apo B (r
      = -0.431, P = 0.002) and between iPTH and Body Mass Index (r = -0.362, P =
      0.009). In conclusion, no significant relationship between iPTH and lipids was
      found in the studied HD patients. These findings suggest that iPTH most probably
      does not play a significant role in the dyslipidemia of renal failure.

PMID- 23168849
TI  - Branched chain amino acid profile in early chronic kidney disease.
AB  - The nutritional status in chronic kidney disease (CKD) patients is a predictor of
      prognosis during the first period of dialysis. Serum albumin is the most commonly
      used nutritional marker. Another index is plasma amino acid profile. Of these,
      the plasma levels of branched chain amino acids (BCAA), especially valine and
      leucine, correlate well with nutritional status. Plasma BCAAs were evaluated
      along with albumin and C-reactive protein in 15 patients of early stages of CKD
      and 15 age- and sex-matched healthy controls. A significant decrease in plasma
      valine, leucine and albumin levels was observed in CKD patients when compared
      with the controls (P <0.05). No significant difference in C-reactive protein
      (CRP) levels was observed between the two groups. Malnutrition seen in our CKD
      patients in the form of hypoalbuminemia and decreased concentrations of BCAA
      points to the need to evaluate the nutritional status in the early stages itself.
      Simple measures in the form of amino acid supplementation should be instituted
      early to decrease the morbidity and mortality before start of dialysis in these
      patients.

PMID- 23168850
TI  - Assessment of cognitive dysfunction in kidney disease.
AB  - Cognitive dysfunction includes reduced mental alertness, intellectual impairment,
      decreased attention and concentration, memory deficits and diminished perceptual
      motor coordination. Chronic kidney disease (CKD) patients may suffer from
      cognitive impairment, which may decrease an individual's quality of life,
      increase resource utilization and result in suboptimal medical care. This study
      was carried out on 120 patients with different stages of CKD from our nephrology
      outpatient clinic divided into three groups: Group I: 50 CKD patients, stage 3
      and stage 4; Group II: 50 end-stage renal disease patients on regular
      hemodialysis with K t/v >1.1; and Group III: 20 acute kidney injury patients,
      followed-up till their renal functions stabilized besides Group IV: 20 healthy
      subjects served as controls. All patients underwent laboratory investigations and
      psychometric tests, which include trial making test part B, digit span test,
      digit symbol test and mini-mental state examination. There was a significant
      difference of mean values of cognitive function tests in Groups I, II and III on
      comparing them with Group IV. Stage 3 CKD scored better than stage 4 CKD, which
      was worse than hemodialysis patients, and lastly acute kidney injury patients had
      mild cognitive impairment, which was restored after recovery. We found an
      association between hemoglobin and cognitive function tests score in the studied
      groups. The degree of cognitive impairment was associated with the severity of
      CKD, and dialysis improved cognitive performance.

PMID- 23168851
TI  - The effects of calcitriol on albuminuria in patients with type-2 diabetes
      mellitus.
AB  - The renin-angiotensin system has a major role in the development of diabetic
      nephropathy (DN). It is reported that vitamin D analogues are able to suppress
      renin excretion. Thus, this study was conducted to determine whether there is any
      correlation between albuminuria as a marker of DN with vitamin D levels in
      diabetic patients. Also, an assessment was made on the effects of vitamin D
      therapy on albuminuria in this group of patients. We conducted this cross
      sectional study on 119 outpatients with type-2 diabetes. The serum levels of 25
      hydroxy vitamin D [25 (OH) D] and the albumin to creatinine ratio were assessed
      in all the study patients. Patients with vitamin D deficiency/insufficiency
      received calcitriol therapy for eight weeks, following which the laboratory tests
      were repeated. The mean age of the study patients was 55.3 +/- 11.2 years, 43
      (36.13%) had vitamin D insufficiency [25 (OH) D <25 ng/mL] and 31 (26.1%) had
      vitamin D deficiency [25 (OH) D <15 ng/mL]. We found a significant correlation
      between 25 (OH) D levels and presence of microalbuminuria (P = 0.04) in patients
      with vitamin D deficiency. Therapy with calcitriol had a beneficial effect on the
      albumin excretion rate, although this change was not significant (P = 0.22).
      However, the effects of calcitriol on reduction of diastolic blood pressure (P =
      0.004), glycosylated hemoglobin (P = 0.014) and levels of total cholesterol (P =
      0.019), low-density lipoprotein (0.04) and high-density lipoprotein (P = 0.001)
      was significant. Our study suggests that vitamin D deficiency has a negative
      effect on albuminuria in diabetic patients, and its replacement may be associated
      with a beneficial effect on the risk factors of DN, such as hyperlipidemia and
      hypertension.

PMID- 23168852
TI  - Indications for nephrectomy in children: a report on 119 cases.
AB  - The objective of the study is to review the indications for nephrectomy in
      children. This study was conducted in the Division of Pediatric Surgery at the
      King Hussein Medical Center, Amman, Jordan, between the years 1997 and 2009. The
      medical records of 119 of 141 patients who underwent nephrectomy were reviewed.
      The patients included 67 males and 52 females, and their ages ranged from two
      months to 13 years. The study patients underwent simple or radical nephrectomy or
      nephron-sparing surgery during the 13-year period. They were studied with regard
      to gender, age, indication for nephrectomy, morbidity and mortality. The
      indications for nephrectomy were divided into benign and malignant conditions. Of
      the 119 nephrectomies performed, 49 patients (41.2%) had malignant conditions and
      70 (58.8%) had a benign etiology. In the benign group, 23.5% of the patients
      underwent nephrectomy for complicated vesicoureteric reflux, urinary tract stones
      or infection (1.6%). Other conditions in this group included ureterocele,
      posterior urethral valve, etc. Benign conditions and ureterocele necessitating
      nephrectomy were predominant in female patients, while pelvi-ureteric junction
      obstruction was predominant in males. The malignant lesions necessitating
      nephrectomy included Wilms tumor and neuroblastoma. The over-all mortality rate
      was nil in the absence of malignancy. Obstructive nephropathy was the main cause
      of nephrectomy in this series, followed by malignancy of the kidney. It remains
      to be seen whether better management will reduce the incidence of nephrectomies
      in preventable cases. It is also important that children with a solitary
      functioning kidney have long-term follow-up.

PMID- 23168853
TI  - Comparison of 24-hour urinary citrate excretion in stone formers and healthy
      volunteers.
AB  - Low urinary citrate excretion is a risk factor in stone formers (SF). This study
      aimed to measure the urinary citrate excretion in SF and healthy volunteers at
      our center from 12 June 2008 to 20 August 2009. There were 28 SF patients (18
      males and ten females) and 27 (18 males and nine females) age-matched healthy
      adult volunteers who participated in this study. Both groups had a similar living
      environment, extrinsic factors, diet and genetic descent. After collecting 24-h
      urine, citrate was measured using an enzymatic kit. Routine urinalysis and 24-h
      creatinine and uric acid were also performed. There was a significant difference
      in urinary citrate excretion level among SF (mean 310, SD 260 mg/L) and normal
      volunteer subjects (mean 800, SD 300 mg/L). By applying the previously defined
      normal values (320 mg/24 h) of urinary citrate in the local population, 43% of
      the SF in our study group was hypocitric, and none among the controls. We
      conclude that prevalence of hypocitraturia in stone formers was higher than that
      in healthy volunteers in our population.

PMID- 23168854
TI  - A retrospective study of the seasonal pattern of urolithiasis.
AB  - This retrospective descriptive study was conducted among patients who presented
      with variable symptoms of urolithiasis at the Department of Surgery and Urology
      of Gulf Medical College Hospital and Research Centre (GMCHRC), Ajman, United Arab
      Emirates (UAE), in order to assess whether the occurrence of urolithiasis
      differed in relation to season, temperature and humidity. A checklist was used
      for abstracting the case record and analysis was performed using PASW 17 version.
      Maximum number of cases was below the age of 40 years, with a male to female
      ratio of 5.2:1. The present study revealed a higher number of cases during summer
      compared with the other seasons, but it was not statistically significant. No
      significant correlation was seen between atmospheric temperature, relative
      humidity and number of cases with urolithiasis. Our study also revealed that the
      admission rate for renal colic was higher in the summer season as against the
      rest of the year, although the difference was not significant. In conclusion,
      urolithiasis is an important public health issue that predominantly affects
      people of the productive age groups. Men are affected more commonly than women.
      No significant seasonal variation in the number of patients with urolithiasis was
      observed in the study.

PMID- 23168855
TI  - Mixed germ-cell testicular tumor in a liver transplant recipient.
AB  - The development of malignancies after solid organ transplants is a well-known
      complication. Cancer is associated with significant consequences for the organ
      transplant patient. It is expected that cancer will surpass cardiovascular
      complications as the leading cause of death in transplant patients within the
      next few years. We report on a 36-year-old male patient who developed mixed germ
      cell testicular tumor seven years after liver transplantation for alcoholic
      cirrhosis. He was treated with orchiectomy, retroperitoneal lymph node dissection
      and post-operative chemotherapy.

PMID- 23168856
TI  - Renal pleomorphic undifferentiated sarcoma: a rarity.
AB  - A 70-year-old male presented with progressive weight loss for eight months.
      Radiological imaging showed a large tumor in the right kidney. The patient
      underwent right open radical nephrectomy and histopathology revealed pleomorphic
      undifferentiated sarcoma (PUS) earlier known as malignant fibrous histiocytoma
      (MFH). One year after surgery, the patient developed pulmonary metastasis.
      Unfortunately, the patient died after six months.

PMID- 23168857
TI  - Bilateral supernumerary kidneys in conjunction with horseshoe anomaly.
AB  - Bilateral supernumerary kidney is a very rare urogenital anomaly, with four cases
      reported in the literature thus far. To the best of our knowledge, bilateral
      supernumerary kidney in conjunction with horseshoe fusion anomaly is not reported
      till date. Herein, we report a 63-year-old male patient with persistent lower
      abdominal pain. Complete radiological evaluation including ultrasound, computed
      tomography scan, excretory urography and retrograde pyelography were done and the
      diagnosis was established. The dilemma faced in the diagnosis and management of
      patients with supernumerary kidneys is discussed.

PMID- 23168858
TI  - Fibrillary glomerulonephritis: a diagnosis not to be missed'.
AB  - Fibrillary glomerulonephritis (Fib GN) is among the newly recognized primary
      glomerular diseases. This rare cause of end-stage kidney disease has
      characteristic electron microscopic findings based upon the deposition of
      randomly distributed (18-22 nm) microfibrills in the mesangium and less
      frequently in the capillary basement membrane. The main differential diagnosis at
      the pathological level is amyloidosis; however, the apple green birefringence
      Congo red positivity of amyloid deposition is not seen in Fib GN. Clinically, the
      patient usually presents with proteinuria of nephrotic range, and the sine qua
      non for the diagnosis of Fib GN is the availability of high-magnification
      electron micrographs. Here is a case report of Fib GN with special emphasis on
      electron microscopy study and its role in the diagnosis.

PMID- 23168859
TI  - Bisalbuminemia during remission of nephrotic syndrome.
AB  - The bisalbuminemia acquired outside of the long-term antibiotic treatment is an
      exceptional event. It is a rare condition characterised by the presence of two
      distinct fractions of serum albumin on electrophoresis. This anomaly reflects the
      presence, at the same time, of a normal albumin and a modified albumin. These
      changes of albumin may be related to various causes. Their association with
      nephrotic syndrome is exceptional. We report a case of bisalbuminemia during a
      period of remission of nephrotic syndrome.

PMID- 23168860
TI  - Laparoscopic trans-peritoneal pyelolithotomy in a pelvic kidney.
AB  - Urinary lithiasis is one of the most common and the oldest known afflictions of
      the urinary tract. The management of renal stones has undergone radical changes
      in recent years, the latest being the minimally invasive procedures like extra
      corporeal shock wave lithotripsy and percutaneous nephrolithotomy, making the
      open surgical procedures relatively obsolete. However, there are situations where
      the above-mentioned minimally invasive procedures prove to be lacking in
      achieving the cure; laparoscopic pyelolithotomy caters to such group of patients,
      e.g. the presence of calculi in malrotated or malpositioned kidneys. Herein, we
      report a case of pelvic kidney with a large calculus managed by laparoscopic
      trans-peritoneal pyelolithotomy.

PMID- 23168861
TI  - Renal ablation using bilateral renal artery embolization for treatment of
      resistant nephrotic syndrome.
AB  - An 18-year-old man presented with severe nephrotic syndrome due to focal
      segmental glomerulosclerosis. His disease failed to remit with corticosteroids,
      calcineurin inhibitors, mycophenolate and rituximab. As his disease progressed
      with time, his anasarca became more resistant to high-dose combination diuretics
      and he developed multiple life-threatening bacterial infections. He was subjected
      to bilateral renal artery embolization with 99.8% alcohol to ablate his kidneys.
      Subsequently, the patient was maintained on hemodialysis and had normal serum
      albumin and did not have further infections. The procedure itself was simple and
      well tolerated, with only a minor post-embolization syndrome.

PMID- 23168862
TI  - Acute interstitial nephritis in patients with viperine snake bite: single center
      experience of a rare presentation.
AB  - Acute renal failure following vasculotoxic viperine snake bites is very common in
      South Asia. Acute tubular necrosis and acute cortical necrosis are the common
      findings, with acute interstitial nephritis (AIN) being a rare presentation. We
      conducted renal biopsies in all patients who were admitted in our institute with
      viperine snake bite-related acute kidney injury (AKI) and who did not improve
      after three weeks of supportive care. Patients who had findings of AIN on renal
      histology were included for this study. Of a total of 42 patients, there were
      five patients (11.9%) with AIN. Our series of five patients is the largest series
      of this rare presentation in the literature. All of these five patients had
      features of severe envenomation, severe AKI network stage of AKI and very high
      antivenom requirements. They had a very prolonged stay in the hospital, and four
      of the five patients developed chronic kidney disease on follow-up. The overall
      outcome in this group was worse as compared with those who did not have AIN. AIN
      following viperine snake bites is not a very rare presentation. The reason for
      the development of this pathology is unclear, but direct venom-related effects
      are possible. This presentation portends a poor overall long-term prognosis as
      demonstrated in our case series.

PMID- 23168863
TI  - Infection with the hepatitis C virus as a risk factor of cardiovascular events in
      the early years after renal transplantation: a single center study from Egypt.

PMID- 23168864
TI  - Laparoscopic live donor nephrectomy: our experience.

PMID- 23168865
TI  - Duodenal microbiasis in children on regular hemodialysis.

PMID- 23168866
TI  - Plasma lipoprotein abnormalities in hemodialysis patients.

PMID- 23168867
TI  - Primary amyloidosis treated with continuous ambulatory peritoneal dialysis.

PMID- 23168868
TI  - Unusual etiology of recurrent urinary tract infection.

PMID- 23168869
TI  - Clinicopathological correlation of primary nephrotic syndrome in adults.

PMID- 23168870
TI  - Nimesulide-induced acute renal failure.

PMID- 23168871
TI  - Renal abscess caused by Escherichia coli.

PMID- 23168872
TI  - IgM nephropathy: clinical features and pathological findings in 36 patients.

PMID- 23168873
TI  - Imidacloprid poisoning presenting as leukoclastic vasculitis with renal and
      hepatic dysfunction.

PMID- 23168874
TI  - Knowledge and attitudes of health care professionals toward organ donation and
      transplantation.
AB  - To identify and assess the level of knowledge and attitudes of health care
      professionals (HCP) in Qatar toward organ donation and transplantation, this
      cross-sectional study was carried out from October 2007 to February 2008 in the
      Accident and Emergency Departments and Intensive Care Units of the hospitals of
      the Hamad Medical Corporation (HMC). A representative sample of 585 HCP working
      in the hospitals of the HMC was approached and 418 staff gave consent to
      participate in the study (71.5%). 36.8% were physicians, 48.6% nurses and 14.6%
      Emergency Medical Service (EMS) technicians. Of the surveyed HCP, 40.7% were
      males and 59.3% were females. Majority of the staff were in the age group of 30
      39 years (58.6%). More than half of the physicians (59.7%) and technicians
      (57.4%) assumed that organs can be bought and sold in the State of Qatar. Most of
      the physicians (76.6%) and nurses (75.9%) knew that brain-dead persons are
      eligible for organ donation, whereas only 57.4% of the EMS technicians thought
      so. Majority of the HCP supported organ donation; physicians (89.0%), nurses
      (82.3%) and technicians (70.5%). The attitude of the physicians (24.0%) and
      nurses (20.2%) to donate a kidney to a family member was very poor compared with
      the attitude of the technicians (44.3%). Although the HCP support organ donation
      (83%), more than half of the physicians (51.3%), nurses (61.6%) and technicians
      (54.1%) wanted to be buried with all their organs intact. The findings, although
      they give cause for hope, suggest that there is much work yet to be done before
      organ donation and transplantation can become fully accepted by the medical
      community in Qatar.

PMID- 23168875
TI  - Urinary tract infections following renal transplantation: a single-center
      experience.
AB  - Urinary tract infection (UTI) is the most frequent infectious complication among
      renal transplant recipients and a frequent cause of bacteremia, sepsis and acute
      graft failure. To evaluate the incidence, risk factors, type of pathogens and
      long-term effect of UTIs on graft and patient survivals in our center, we
      performed a retrospective cohort study reviewing the medical records of patients
      who received a renal transplant at our center from June 1986 to December 2009,
      excluding patients who lost their grafts in the first month due to arterial or
      veins thrombosis and acute antibody-mediated rejection. We studied 393 kidney
      transplanted recipients; at least one UTI occurred in 221 (53.69%) patients
      during the follow-up period. The most frequent pathogens isolated in urine
      culture were Escherichia coli (n = 39, 18.4%) and Klebsiella pneumonia (n = 31,
      14.6%). When patients with UTIs were compared with those without UTIs, female
      gender and use of mycophenolate mofetil or azathioprine seemed to be risk factors
      for UTIs on univariate analysis. However, female gender was the only independent
      risk factor on multivariate analysis RR = 1.964 (1.202-3.207), P = 0.007. This
      study confirmed that UTIs remain a major problem in renal transplant recipients,
      and female gender was the only independent risk factor.

PMID- 23168876
TI  - Acute kidney injury requiring hemodialysis in the tropics.
AB  - The morbidity and mortality from acute kidney injury (AKI) have remained
      relatively high over the last six decades. The triad of infections, nephrotoxins
      and obstetric complications are still major causes of acute kidney injury in the
      tropics. This retrospective study is a five-year audit of acute renal failure
      (ARF) (or stage 3 AKI) in patients requiring hemodialysis at the renal unit of
      the Department of Medicine of the Ladoke Akintola University of Technology
      (LAUTECH) Teaching Hospital, Osogbo, Nigeria. A total of 80 patients with AKI
      were treated over a five-year period at our center, of which 45 (56.2%) were in
      ARF, i.e. stage 3 AKI requiring hemodialysis. There were 24 males and 21 females.
      The most common cause of ARF among the patients was sepsis syndrome 16 (35.5%),
      while pregnancy-related cases accounted for 15 (33.3%) and nephrotoxins for 6
      (13.3%). Five (33%) of the 15 pregnancy-related patients survived, and all were
      cases of septic abortion. Of the other 10 patients that did not survive, three
      (30%) had post-partum hemorrhage and seven (70%) post-partum eclampsia. In all,
      the mortality rate among our AKI presenting for hemodialysis at our center over a
      given year period was 28.8%. Majority of these were eclampsia related. The causes
      of ARF still remain the same in the tropics, eclampsia portends poor prognosis.
      Concerted efforts should be made at limiting this trend by active preventive
      services and early recognition of high-risk obstetrics cases.

PMID- 23168877
TI  - Evaluation of microalbuminuria in relation to asymptomatic bacteruria in Nigerian
      patients with sickle cell anemia.
AB  - Studies have identified microalbuminuria (MA) and asymptomatic bacteruria (ASB)
      as co-morbid factors in sickle cell anemia (SCA). However, the relationship
      between these comorbid factors remains unclear and data are lacking for Nigerian
      patients. This study determined the prevalence of MA and ASB in a cohort of
      patients with SCA in a steady state, in Lagos, Nigeria. Early morning mid-stream
      urine samples were collected in sterile bottles from 103 patients comprising 48
      males and 55 females with a mean age of 10.4 years. Aerobic culture and colony
      count of organisms was done using conventional methods. Serum creatinine and
      hematological indices, including irreversibly sickled cells (ISC), were also
      assayed. Of the 103 urine samples screened, 23 (22.3%) had albuminuria (ALB), and
      consisted of nine males and 14 females (P > 0.05); 16.5% of the cases had MA (P
      <0.05). Age at onset of MA was seven years, and children accounted for 23.5% of
      all cases with ALB (P >0.05). The prevalence of confirmed ASB was 14.6%, with
      females accounting for 14 of 19 probable ASB cases (P <0.05). Univariate
      regression analysis demonstrated a significant (P <0.05) association between age
      at onset of MA, hemoglobin level, reticulocyte count, ISC and occurrence of ASB,
      but with only ISC evolving as an independent predictor. Twenty-eight bacterial
      isolates predominated by Escherichia coli (39.3%; P <0.05), of whom 89.3% were
      multi-drug resistant, were recovered from the ASB urine samples. In conclusion,
      both MA and ASB are common in Nigerian SCA patients, with the former occurring
      from the first decade of life.

PMID- 23168878
TI  - Relaxations in heterolanthanide dinuclear single-molecule magnets.
AB  - A heterospin dinuclear complex
      [Dy(0.87)Yb(1.13)(H(2)cht)(2)Cl(4)(H(2)O)(MeCN)].MeCN shows shifts of the
      relaxation barriers with respect to the barriers observed in homospin Dy(2) and
      Yb(2) isostructural complexes. The origin of slow relaxation in the latter two
      compounds was elucidated by ab initio calculations.

PMID- 23168879
TI  - Sensate vastus lateralis muscle flap for reconstruction of complex ischial sore.

PMID- 23168881
TI  - Pleuroscopy: a window of "opportunity".

PMID- 23168880
TI  - Developing normalized strength scores for neuromuscular research.
AB  - INTRODUCTION: The Accurate Test of Limb Isometric Strength (ATLIS) device can
      reliably measure the strength of 12 muscle groups using a fixed load cell. The
      purpose of this study was to analyze ATLIS data from healthy adults to calculate
      an individual's predicted strength scores. METHODS: ATLIS data were collected
      from 432 healthy adults. Linear regression models were developed to predict each
      muscle group's strength. The R-squared statistic assessed variability accounted
      for by the models. RESULTS: Simple main effects models stratified by gender were
      used to establish regression equations for each muscle using factors of age,
      weight, and height. CONCLUSIONS: Normalizing raw strength scores controls for
      biometric factors, thus enabling meaningful comparisons between subjects and
      allowing each muscle to contribute equally to a summary score. Normalized scores
      are easily interpreted for broad clinical uses, and derived summary scores
      establish individuals' disease progression rates using a common scale, allowing
      for more efficient clinical trials.

PMID- 23168882
TI  - Navigation guidance for bronchoscopy: "are we there yet?".

PMID- 23168883
TI  - Utility of semirigid thoracoscopy in the diagnosis of pleural effusions: a
      systematic review.
AB  - BACKGROUND AND OBJECTIVE: Pleural effusion of undetermined etiology (PEUE), where
      blind pleural aspirate/biopsy fails to yield an answer, often needs histologic
      study for a definitive diagnosis. Several studies have shown the potential
      utility of medical thoracoscopy (MT) in PEUE; results, however, are not uniform
      and a majority are available for rigid thoracoscopy. We sought to determine the
      diagnostic accuracy of the relatively new technique of semirigid thoracoscopy in
      PEUE through this systematic review. METHODS: The electronic search was carried
      out in PubMed without language restriction. References of relevant records and
      abstracts were hand searched. Articles were selected based on the following
      criteria: (1) prospective study, (2) based on original research, (3) enrolled
      consecutive patients with PEUE, (4) full paper available in English, (5) MT
      carried out under local anesthesia (LA) using semirigid (flex-rigid) instrument,
      and (6) reported sufficient data to construct a 2infinity2 contingency table. We
      assessed the study quality and extracted data independently and in duplicate
      using a standardized data extraction form. RESULTS: Five studies met the
      inclusion criteria, encompassing 154 patients. Pooled sensitivity (95% CI) was
      0.97 (0.92-0.99), specificity (95% CI) was 1.00 (0.69-1.00), positive likelihood
      ratio (95% CI) was 5.47 (1.11-16.86) and negative likelihood ratio (95%CI) was
      0.08 (0.04-0.18). No major complications or mortality was noted. CONCLUSION:
      Semirigid thoracoscopy seems to be a safe, simple, and accurate tool for
      undiagnosed pleural effusions. It is well tolerated and is devoid of major
      complications. Further studies with sound methodology will further help to define
      the future role of this procedure.

PMID- 23168884
TI  - Factors Influencing the Diagnostic Yield of Endobronchial Ultrasound-guided
      Transbronchial Needle Aspiration.
AB  - We describe the diagnostic performance of endobronchial ultrasound-guided
      transbronchial needle aspiration (EBUS-TBNA) in a heterogeneous population of
      patients with mediastinal lymphadenopathy secondary to suspected cancer (lung and
      nonlung) or recurrence after cancer therapy in a large academic cancer institute.
      A review was done of all patients referred for real-time EBUS-TBNA over an 18
      month period at our institution. Cytological analysis of EBUS-TBNA aspirates was
      compared with a reference standard of definitive pathologic tissue diagnosis or a
      composite of >=6 months' clinical follow-up with radiographic imaging. Adequate
      tissue was obtained in 225/236 procedures (95.3%) and a reference standard was
      available in 214. The overall diagnostic yield of EBUS-TBNA in those procedures
      with a reference standard was 87.4%. The sensitivity, specificity and diagnostic
      accuracy of EBUS-TBNA for malignancy was 86.1%, 100% and 92.9%, respectively. The
      sampling accuracy of EBUS-TBNA decreased with lymph node size <=5 mm and with
      paratracheal location. Other factors, such as airway distortion and
      calcification, are also associated with less accurate EBUS-TBNA results. In a
      diverse population of patients with suspected cancer or recurrence, EBUS-TBNA is
      minimally invasive and highly accurate. Factors such as lymph node size and
      location influence the result of EBUS-TBNA.

PMID- 23168885
TI  - Delays and efficiency in the bronchoscopy suite: perception meets reality.
AB  - Procedural delays or late start times in the bronchoscopy suite can impact
      operational efficiencies and potentially patient care. To date, little data have
      been published examining the potential causes of such delays or ways to prevent
      them in the bronchoscopy unit. In a quality assessment project at a major medical
      center, we surveyed members of the bronchoscopy team to determine perceptions of
      the existence of delays in the bronchoscopy suite and possible causes. For
      comparison, we prospectively observed procedures in the bronchoscopy suite and
      retrospectively reviewed the records of past procedures to identify delays in the
      delivery of care. A total of 31 procedures were prospectively observed, with
      delays (defined a priori as procedures beginning 15 minutes after the scheduled
      start time) occurring 80% of the time. Two hundred thirty-four procedures were
      retrospectively reviewed, with delays occurring 71% of the time. In both data
      sets, the largest portion of time the patient spent in the bronchoscopy suite was
      during the preprocedure period. Delays often occur in the bronchoscopy suite,
      with preprocedure activities identified as an area for potential improvement.

PMID- 23168886
TI  - Usefulness of flexible bronchoscopy outside the hospital setting.
AB  - INTRODUCTION: Flexible bronchoscopy (FB) is a procedure usually carried out in
      the hospital setting. Occasionally, home hospitalized (HH) patients or those at
      long-term acute care facilities (LTACF) are not likely to be transferred to
      hospitals, either because they refuse to be transferred or because such transfer
      may be risky or complex. Under such circumstances, FB could be performed in both
      sites, especially in technically simple procedures or with a low complication
      rate. OBJECTIVES: The purpose of this study was to assess whether FB carried out
      at LTACF or in the home is safe, useful, well tolerated, and free of
      complications. PATIENTS AND METHODS: This study analyzed FB carried out at LTACF
      or in HH patients from October 2007 to November 2009. The procedures chosen were
      structural and functional assessment of the airway (SFAA) owing to potential
      tracheal stenosis, tracheomalacia, tracheo-esophageal fistula, phonation or
      swallowing disorders, and as earlier control to decannulation. Other techniques
      used were: aspiration of tracheobronchial mucus (ATBM), complex tracheostomy tube
      changes (TTC), tracheal prosthesis control (TPC), evaluation of mild hemoptysis
      (MH), and bronchoalveolar lavage (BAL). FB was carried out under local
      anesthesia. The endoscope entered through the nose, mouth, tracheostomy tube,
      and/or T-tracheal prosthesis. RESULTS: Thirty-three FB were carried out in 25
      LTACF patients: 33 SFAA, 3 MH, 3 TTC, 2 ATBM, 1 BAL, and 2 TPC. Ten FB were
      carried out in 8 HH patients: 10 SFAA, 4 TTC, and 7 ATBM. Procedures were well
      tolerated. There was no evidence of complications. CONCLUSIONS: FB carried out
      outside the hospital setting can be done safely and effectively, at least in a
      selected group of patients and carrying out selected procedures.

PMID- 23168887
TI  - Repair costs for endobronchial ultrasound bronchoscopes.
AB  - BACKGROUND: The development of endobronchial ultrasound (EBUS) has revolutionized
      the diagnostic approach to lung cancer and mediastinal lymphadenopathy. The
      capital costs associated with implementing EBUS are easily obtained from
      manufacturers, but the ongoing maintenance and repair costs are unknown.
      OBJECTIVE: The purpose of this study was to delineate the maintenance and repair
      costs associated with EBUS. METHODS: For the period between October 2005 and June
      30, 2009, the number of procedures and the maintenance and repair costs for both
      EBUS and flexible bronchoscopes were recorded. Two BF-160UCF-OL8 (Olympus,
      Canada) linear convex EBUS bronchoscopes were used for EBUS procedures during the
      course of the study. Total costs were calculated on a yearly basis and on a per
      procedure basis for EBUS and standard bronchoscopes and are presented in Canadian
      and US dollars ($1 CAN=$0.88 USD). RESULTS: During the period of October 2005 and
      June 2009, a total of 949 linear convex EBUS procedures and 2767 flexible
      bronchoscopies were carried out. During this period, 13 separate repair issues
      were encountered with the EBUS bronchoscopes and control unit. The total cost for
      maintenance and repair of the EBUS and flexible bronchoscopes was $110,151.46
      ($96,933.28 USD) and $67,301.49 ($59,225.31 USD), respectively. The average cost
      per procedure for EBUS and flexible bronchoscopy was $116.00 ($102.08 USD) and
      $24.32 ($21.42 USD), respectively. CONCLUSIONS: The cost of EBUS repairs per
      procedure is significant and illustrates the importance of understanding the
      ongoing maintenance issues inherent in these delicate pieces of medical
      equipment.

PMID- 23168888
TI  - Effects on respiratory mechanics of bronchoalveolar lavage in mechanically
      ventilated patients.
AB  - INTRODUCTION: Inconsistent findings have been reported about the effects of
      bronchoalveolar lavage (BAL) on respiratory mechanics. The aims of this study
      were to study the effects of BAL on respiratory mechanics in mechanically
      ventilated patients with suspected pneumonia and to find out whether these
      effects are related to the extension of radiographic infiltrate and preceding
      respiratory mechanics measurements. METHODS: Bronchoscopy BAL was performed with
      150 mL of sterile isotonic saline in 3 aliquots of 50 mL. Respiratory mechanics
      parameters were measured by the rapid airway occlusion technique, immediately
      before and after BAL and 90 minutes later. Patients were classified according to
      unilateral or bilateral radiological infiltrate occurrence. RESULTS: Fifty
      critically ill patients undergoing mechanical ventilation were included.
      Respiratory system compliance (Crs) decreased from 43.32+/-13.17 mL/cm H2O to
      33.02+/-9.56 mL/cm H2O (P<0.01) and airway resistance increased from 15.16+/-7.04
      cm H2O/L/s to 17.54+/-9.40 cm H2O/L/s (P<0.05) immediately after BAL; 90 minutes
      later both the parameters returned to the pre-BAL values. Patients who showed a
      greater than 20% decrease in Crs had a higher pre-BAL Crs than patients with a
      less severe decrease (49.85+/-10.7 mL/cm H2O vs. 35.65+/-11.67 mL/cm H2O;
      P<0.01). However, neither pre-BAL airway resistance nor the extension of the
      radiographic infiltrates was related to the changes in respiratory mechanics.
      CONCLUSIONS: BAL in mechanically ventilated patients can lead to a significant,
      although transitory, deterioration in pulmonary mechanics, characterized by a
      decrease in Crs and by an increase in airway resistance. Patients with better
      initial Crs showed the most severe affectation.

PMID- 23168889
TI  - Endoscopic tracheoplasty: segmental tracheal ring resection in a porcine model.
AB  - Endoscopic tracheoplasty is used for the relief of airway obstruction because of
      several benign conditions such as postintubation stenosis, inflammatory disorders
      such as Wegener granulomatosis, and benign neoplastic processes. Several
      endoscopic treatment modalities exist for these conditions, all with good initial
      results. However, recurrence is common and often requires frequent
      reintervention. Endoscopic segmental tracheal ring resection is a novel
      therapeutic approach that could potentially provide a durable solution.
      Endoscopic segmental tracheal ring resection was performed in 3 Yorkshire pigs
      under general anesthesia. A combination of bipolar cautery and sharp dissection
      was used to resect 25% to 33% of the circumference of a single tracheal ring.
      Technical success was achieved in all 3 animals with no intraoperative
      complications. Full-thickness excision, including the anterior perichondrium, was
      performed in 1 animal without violation of the pretracheal fascia, with no
      subcutaneous emphysema or clinically apparent pneumothorax. Average operative
      time was 31 minutes and estimated blood loss was minimal. Heart rate, oxygen
      saturation, and peak airway pressures were maintained within normal ranges during
      the procedure and for the 60-minute postoperative period. Histologic analysis of
      the resected specimen confirmed complete thickness excision of the segment of
      tracheal cartilage. Endoscopic tracheoplasty by segmental tracheal ring resection
      is a safe and feasible technique in a porcine model. Long-term durability could
      potentially outlast other endoscopic techniques for the treatment of bening
      tracheal stenosis. Survival studies in a porcine model of tracheal stenosis must
      be performed to assess the long-term outcomes of this approach.

PMID- 23168890
TI  - Retained sutures in the trachea.
AB  - A 57-year-old man was evaluated for mucosal irregularity involving the anterior
      tracheal wall detected on a routine chest computed tomography scan performed for
      lung transplant evaluation. He had a history of hypercapneic respiratory failure
      requiring tracheostomy, yet he had been successfully decannulated several months
      before presentation. Flexible bronchoscopy revealed retained suture material at
      the earlier tracheostomy site, which was successfully clipped and removed.

PMID- 23168891
TI  - Lobular capillary hemangioma of the trachea: the second case.
AB  - A benign lesion also known as pyogenic granuloma, lobular capillary hemangioma
      (LCH) is relatively common a cutaneous and mucosal lesion. Earlier reports of LCH
      within the larynx and trachea have been reviewed and determined to be granulation
      tissue with an earlier history of airway trauma. Histopathologic review varies
      over time in this vascular lesion. Earlier, there is an extensive inflammatory
      infiltrate similar to granulation tissue; however, this becomes fibromyxoid as
      the lesion matures. An appropriate history is therefore mandatory to exclude any
      potential trauma, which would lead to granulation tissue as a result of injury.
      There is only one case reported earlier in the literature of LCH in the trachea.

PMID- 23168892
TI  - Tracheopathia osteochondroplastica: two unusual cases.
AB  - We describe 2 unusual cases of tracheopathia osteochondroplastica (TPO), one of
      them presenting with lung carcinoma and the other at an uncommon age. A 74-year
      old man presented with chronic bronchitis and a left lower lobe lesion as
      detected on chest computed tomography. Flexible bronchoscopy revealed multiple
      calcified nodular lesions involving the anterior-lateral walls of the trachea and
      main bronchi. Histologic analysis of the tracheal nodules confirmed the presence
      of TPO. Squamous cell carcinoma was diagnosed by transthoracic needle aspiration
      of the pulmonary nodule. The relevance of coexistence of these 2 conditions
      remains unknown. Our second case was in a young man who presented with persistent
      cough and a chest computed tomography scan revealing multiple tracheal nodules.
      Numerous hard tracheal nodules distributed around the lower trachea and main
      bronchi were observed at flexible bronchoscopy. When the cough and dyspnea
      persists despite conventional empiric treatment, uncommon tracheobronchial
      pathologies, such as TPO, should be considered.

PMID- 23168893
TI  - Acute respiratory distress syndrome after airway anesthesia with lidocaine.
AB  - Adequate anesthesia of the upper and proximal lower airways is a critical
      prerequisite for a smooth and successful bronchoscopic procedure. Lidocaine is
      the most commonly used local anesthetic agent for flexible bronchoscopy. Adverse
      reactions to this agent have rarely been reported. Nevertheless, we recently
      observed a life-threatening reaction to airway lidocaine anesthesia in a 33-year
      old man who was to undergo flexible bronchoscopy for the evaluation of an
      intrathoracic lymphadenopathy. Before the procedure, the patient developed
      noncardiogenic pulmonary edema. Only 2 such cases after airway anesthesia with
      nontoxic doses of lidocaine for a bronchoscopic procedure have been reported in
      the literature. Unlike in these cases, the episode was brief and self-limiting,
      with adverse reaction confined to the respiratory tract without development of
      shock or systemic involvement.

PMID- 23168894
TI  - A bronchoscopic oddity: nodular tracheobronchial amyloidosis.
AB  - Tracheobronchial amyloidosis is a rare disorder of unknown cause associated with
      the extracellular deposition of amyloid protein in a characteristic spatial
      structure of beta-sheet fibrils assembled into bundles. We present a case that
      represents the nodular form of tracheobronchial amyloidosis, which is the least
      common form of pulmonary amyloidosis with less than 20 cases reported so far.
      Patients with tracheobronchial amyloidosis may present with symptoms of dyspnea,
      localized wheezing, cough, hemoptysis, or recurrent pneumonias. The mainstay of
      the therapy is debridement of the symptomatic luminal obstruction with neodymium
      doped yttrium aluminium garnet laser therapy. Other treatment strategies include
      airway stenting, external beam radiation therapy, bypass tracheostomy, or open
      surgical resection.

PMID- 23168895
TI  - Tracheal obstruction as a complication of tracheostomy tube malfunction: case
      report and review of the literature.
AB  - Tracheostomy is a procedure frequently used in the intensive care unit for
      prolonged ventilatory support, long-term airway maintenance, and to prevent the
      complications of long-term translaryngeal intubation. It is believed that it
      eases patient care and improves the process of weaning from mechanical
      ventilation. The timing of tracheostomy is controversial and most physicians
      prefer translaryngeal intubation for needs of up to 10 days and a tracheostomy if
      an artificial airway for more than 21 days is anticipated. Tracheostomy can be
      associated with numerous acute (perioperative or postoperative) complications.
      Some of these complications continue to be a problem after the placement of the
      tracheostomy tube, and there are specific late complications that have clinical
      relevance. To our knowledge, there has been no description of a malfunctioning
      tracheostomy tube leading directly to complications and we are reporting the
      first case.

PMID- 23168896
TI  - A 39-year-old man with fevers, cough, and right upper lobe cavitory lesion in
      lung.
AB  - In this case report, we present a patient who had an endobronchial lesion that
      was found to be caused by Rhodococcus equi, earlier known as corynebacterium.
      Although this organism has been reported to infect immunocompromised patients,
      including several patients with acquired immune deficiency syndrome, it has
      rarely been reported to present as an endobronchial lesion.

PMID- 23168897
TI  - Localization and treatment of bronchopleural fistula through capnography.
AB  - Bronchopleural fistula (BPF) is a feared complication in the setting of
      pneumonectomy, lobectomy, and pulmonary infection. The development of BPFs
      significantly increases morbidity and mortality, and their treatment is
      complicated, multifaceted, and variable in success. Recently, the use of fibrin
      glues, acrylic glues, and endobronchial valves through bronchoscopy has allowed
      for minimally invasive treatment, sparing the patient surgical intervention.
      Results in the literature for these modalities have been mostly positive in a
      variety of clinical scenarios. Regardless of the therapeutic interventions used,
      proper diagnosis and localization of these fistulas is essential. These
      modalities have traditionally included installation of methylene blue in the
      pleural space, balloon occlusion, and ventilation scintigraphy. Here, we report
      the successful localization and treatment of a BPF through the use of localized
      bronchoscopic capnography in a 30-year-old woman with a complicated BPF. Initial
      attempts to localize the fistula with Fogarty catheter balloon occlusion were
      unsuccessful, as multiple segments were involved. Ultimately, with a capnographic
      catheter, the precise segments could be identified and subsequently occluded with
      acrylic glue. Air leak and pneumothorax resolved, chest tubes were removed
      without complication, and the patient was discharged 2 days after the procedure.

PMID- 23168898
TI  - Major airway laceration secondary to endobronchial ultrasound transbronchial
      lymph node biopsy.
AB  - A 48-year-old woman underwent complete mediastinal lymph node staging for non
      small-cell lung cancer. After convex endobronchial ultrasound (EBUS)-guided
      transbronchial biopsy of the subcarinal lymph node station (station no. 7), it
      was noted that a laceration had occurred in the left mainstem bronchus. The tear
      occurred at the medial cartilaginous-membranous junction, seemed to be full
      thickness into the mediastinum, and was approximately 1.5cm long. The cytologic
      results of all lymph node biopsies were negative and the patient underwent right
      upper and middle lobe bilobectomy 12 hours after the EBUS procedure. This is the
      first report of a serious airway injury occurring during convex EBUS lymph node
      biopsy.

PMID- 23168899
TI  - Use of autologous bronchial cartilage to repair an intraoperative bronchial
      airway defect after pneumonectomy for lung mesothelioma.
AB  - Tracheobronchial defects may occur intraoperatively because of surgical trauma
      after resection of thoracic tumors. The repair of large, circumferential
      tracheobronchial defects with tissue loss may pose a major challenge. In an
      effort to solve this problem, different techniques have been used with little
      success. Attempts with foreign materials, nonviable tissues, autogenous
      noncartilaginous tissues, tissue engineering, and allotransplantation have all
      been associated with disappointing or suboptimal results. In each category,
      biologic problems are noted. Hence, the reconstruction and substitution of large,
      circumferential tracheobronchial defects has so far remained an unsolved surgical
      dilemma. We report a unique case in which an airway defect in the bronchus, made
      inadvertently intraoperatively, was repaired using autologous bronchial cartilage
      obtained from the resected specimen. In the literature, autologous bronchial
      cartilage has never been used before in reconstructing a large tracheobronchial
      defect.

PMID- 23168900
TI  - A large ruptured mediastinal cystic teratoma.
AB  - A 51-year-old woman presented with a 2-month history of intermittent cough and
      precordial chest pain associated with shortness of breath. Initial chest-x-ray
      revealed a large well-circumscribed mass in the left perihilar region and
      consolidation of left lower lobe. Computed tomography scan of the chest revealed
      a large irregular fluid-filled mass occupying the left hemithorax, causing a
      mediastinal shift to the right, and a left pleural effusion. A pigtail was
      inserted; pleural fluid was exudative without evidence of malignant cells. Left
      thoracotomy revealed an anterior mediastinal mass of 20 cm in diameter adherent
      to the pericardium, pleura, and lung. Pathologic examination showed a variety of
      cell lines consisting of respiratory mucosa, mucous glands, cartilage, smooth
      muscle, adipose tissue, and pancreatic tissue, results consistent with a mature
      teratoma. Mature cystic teratomas are usually benign in nature and represent 60%
      to 70% of mediastinal germ cell tumors; they are found most commonly in young
      adults. The anterior mediastinum is the most common site for these types of
      tumors. Rupture of a mediastinal cystic teratoma is a rare event and can be a
      life-threatening condition. The treatment is mainly surgical, with an excellent
      prognosis such as in our patient.

PMID- 23168901
TI  - A new technique for the examination of tracheal tumors: the bronchoscopic turned
      around procedure.
AB  - Flexible bronchoscopy is useful for confirming an endotracheal tumor. However,
      observation of the distal end of the tumor is difficult because of the presence
      of the lesion itself. Here we describe a technique that we termed "bronchoscopic
      turned around procedure," which can be used to observe the distal extent of the
      lesion using an ultrathin bronchoscope. The scope is passed distal to the
      endotracheal tumor and is flexed upward by 180 degrees in the trachea for full
      visualization of the distal extent of the lesion and the airway anatomy. We found
      this procedure to be an effective technique to assess surgical candidates by
      confirming the surface structure of the tracheal lumen, which cannot be obtained
      by computed tomography or virtual bronchoscopy.

PMID- 23168902
TI  - Tools of the Trade: A Novel Bronchoscope With a Built-in Miniature Video Screen,
      Camera, and Light Source.
AB  - OBJECTIVE: To evaluate the performance of a mobile bronchoscope with miniature
      video screen, light source, and a digital camera. DESIGN: Prospective study.
      SETTING: Inpatient and outpatient tertiary care center. INTERVENTIONS: None.
      PATIENTS: Twenty patients who were undergoing diagnostic or therapeutic
      bronchoscopy from May 2009 to July 2009. MEASUREMENTS AND MAIN RESULTS: Thirteen
      patients underwent bronchoscopy via the oral and nasal approach, 2 via a
      tracheostomy, and 5 via an endotracheal tube or laryngeal mask airway. The scope
      was also used in the placement of a percutaneous tracheostomy tube and in the
      operating room for 3 procedural endotracheal intubations. The overall performance
      of mobile bronchoscope was satisfactory. The majority of difficulties encountered
      by the bronchoscopists came from the performance of the monitor. The main issue
      was the need to turn the screen to view the image in an upright position.
      CONCLUSIONS: The Airway Mobile Scope is well suited for airway examination and
      interventions often needed in emergency rooms, intensive care units, operating
      rooms, and office settings. The ease of use of the bronchoscope could be enhanced
      with small changes to the display of the image on the LCD screen.

PMID- 23168903
TI  - A brief comment on the history of bronchoscopy in Mexico.

PMID- 23168904
TI  - Infectious Risk Enhanced Because of Endobronchial Ultrasound-guided
      Transbronchial Needle Aspiration of Bronchogenic Cysts.

PMID- 23168905
TI  - Influence of bracken fern (Pteridium caudatum L. Maxon) pre-treatment on
      extraction yield of illudane glycosides and pterosins.
AB  - INTRODUCTION: Bracken (Pteridium spp) illudane glycosidess are labile
      biologically active terpenoids that undergo decomposition in mild alkali or acid,
      heat and enzymatic reactions. Hypothetically, quantitation of these weakly
      chromophoric carcinogens may be challenged by plant sample preparation procedures
      that may alter the yield of isolates. OBJECTIVE: To study the influence of common
      plant sample pre-treatments on the recovery of Pteridium caudatum illudane
      glycoside carcinogens, ptaquiloside (1a), caudatoside (1c) and ptaquiloside Z
      (1d), and associated pterosins A, B and Z (2a, b, c) using HPLC-DAD. METHOD:
      Bracken fronds were divided in equal left/right sections. One section was
      subjected to high vacuum desiccation (VD) and the other to freeze-drying (FD),
      air drying at room temperature (AD) for 7 days, air drying at 70  degrees C for
      72 h (HD), or no treatment (fresh frond, FF). Quantitation was achieved by brief
      hot-water extraction, base-acid transformation of 1a, 1c and 1d to 2a, b, c and
      HPLC-DAD analysis against standards. RESULTS: Substantial differences in
      extraction yields were found for all illudane glycosides in the order FF > FD ~
      VD > AD > HD. Illudane instability to HD was 1c > 1d > 1a. Significant losses
      also were recorded in yields of Pterosins A, B and Z. CONCLUSION: Glycoside
      extraction suffers from substantial yield loss of all illudane glycosides and
      indigenous pterosins in all sample pre-treatments studied relative to fresh frond
      material.

PMID- 23168906
TI  - Orthotopic small bowel transplantation in rats.
AB  - Small bowel transplantation has become an accepted clinical option for patients
      with short gut syndrome and failure of parenteral nutrition (irreversible
      intestinal failure). In specialized centers improved operative and managing
      strategies have led to excellent short- and intermediate term patient and graft
      survival while providing high quality of life (1,3). Unlike in the more common
      transplantation of other solid organs (i.e. heart, liver) many underlying
      mechanisms of graft function and immunologic alterations induced by intestinal
      transplantation are not entirely known(6,7). Episodes of acute rejection, sepsis
      and chronic graft failure are the main obstacles still contributing to less
      favorable long term outcome and hindering a more widespread employment of the
      procedure despite a growing number of patients on home parenteral nutrition who
      would potentially benefit from such a transplant. The small intestine contains a
      large number of passenger leucocytes commonly referred to as part of the gut
      associated lymphoid system (GALT) this being part of the reason for the high
      immunogenity of the intestinal graft. The presence and close proximity of many
      commensals and pathogens in the gut explains the severity of sepsis episodes once
      graft mucosal integrity is compromised (for example by rejection). To advance the
      field of intestinal- and multiorgan transplantation more data generated from
      reliable and feasible animal models is needed. The model provided herein combines
      both reliability and feasibility once established in a standardized manner and
      can provide valuable insight in the underlying complex molecular, cellular and
      functional mechanisms that are triggered by intestinal transplantation. We have
      successfully used and refined the described procedure over more than 5 years in
      our laboratory (8-11). The JoVE video-based format is especially useful to
      demonstrate the complex procedure and avoid initial pitfalls for groups planning
      to establish an orthotopic rodent model investigating intestinal transplantation.

PMID- 23168907
TI  - The intriguing reaction of aromatic sulfonyl phthalimides with gold surfaces.
AB  - We report on a series of arene sulfonyl phthalimides which were prepared and used
      to modify polycrystalline gold and Au(111) gold surfaces. Three investigated
      compounds are the p-iodo-, the p-methoxy-, and the p-fluoro-benzenesulfonyl
      phthalimides. X-ray photoelectron spectroscopy (XPS), cyclic voltammetry (CV),
      and scanning tunneling microscopy (STM) studies were used to characterize the
      modified surfaces. The XPS data show that all three investigated compounds
      decompose on gold surfaces. The decomposition leads to the adsorption of sulfur
      and ejection of the other groups except for the p-iodo compound, which also leads
      to the deposition of iodine. The cyclic voltammetry data confirm these results
      and show that high coverage values of deposited sulfur are obtained. High
      resolution STM imaging showed a dynamic behaviour of sulfur on gold for all
      compounds. Movement of sulfur species on the Au(111) surface is observed. Various
      phases including a new 'zig-zag' pattern and a new 2 : 1 line pattern are
      presented. Sequential STM imaging also showed movement of one area of sulfur
      while another remains static. These results are important because (i) they
      provide direct experimental evidence that these hexavalent sulfur compounds react
      with gold surfaces breaking all sulfur chemical bonds, (ii) they show that
      sulfonyl phthalimides can be used as efficient precursors for the deposition of
      sulfur on gold, and (iii) very importantly they show the adlayer nature of the
      sulfur modified gold surface which has been a heavily debated question.

PMID- 23168909
TI  - Psychotic symptoms in patients with borderline personality disorder:  prevalence
      and clinical management.
AB  - PURPOSE OF REVIEW: The aim of this article is to review findings on the
      prevalence, phenomenology and treatment of psychotic features in borderline
      personality disorder (BPD), and to discuss factors that might be related to their
      occurrence. RECENT FINDINGS: Of patients with BPD about 20-50% report psychotic
      symptoms. Hallucinations can be similar to those in patients with psychotic
      disorders in terms of phenomenology, emotional impact, and their persistence over
      time. Although more research is needed on the exact nature of psychotic phenomena
      in patients with BPD, terms like pseudo-psychotic or quasi-psychotic are
      misleading and should be avoided. Childhood trauma might play an important role
      in the development of psychotic symptoms in patients with BPD, as in other
      populations. More research is necessary on the role of comorbid disorders,
      especially posttraumatic stress disorder (PTSD). Atypical antipsychotics seem to
      be beneficial in some patients; evidence on psychotherapy of psychotic symptoms
      is sparse. SUMMARY: Psychotic symptoms, especially hallucinations, seem to be an
      important feature of BPD. More research on potential mediators and adequate
      treatment approaches for psychotic symptoms in BPD is needed, and current
      diagnostic systems might require revision to emphasise psychotic symptoms.

PMID- 23168912
TI  - Pseudomorphic transformation of amorphous silica microtubes into mesoporous MCM
      41 type silica tubes. Synthesis, characterization and surface functionalization
      with titania, vanadia and zirconia.
AB  - Silica tubes with MCM-41 type mesostructures were successfully synthesized by a
      combination of the Stoeber process and a pseudomorphic transformation using
      electrospun macrosized polystyrene fibres as structure directing templates. Two
      different morphologies of mesoporous silica tubes are accessible with this
      method: a hollow morphology with tunable silica wall thickness and with a
      mesoporous silica shell structure and a core containing amorphous silica. All one
      dimensional tube like porous silica materials have a high specific surface area
      of approximately 1000 m(2) g(-1) with well-ordered hexagonal mesopores. Grafting
      of Ti, V and Zr metallocene dichloride molecular complexes has been employed
      resulting in the deposition of titanium-, vanadium-, zirconium-oxide in the
      interior of the silica tubes after ceramisation of the green body composites. The
      respective oxides were coated on top of the inner mesoporous silica surface of
      the tubes. Such silica based hybrids might be potential support materials in
      heterogeneous catalysis (e.g. vanadia) as well as interesting catalysts for
      photocatalysis (for TiO(2), ZrO(2)). All materials were characterised by X-ray
      diffraction (SAXS and XRD), nitrogen adsorption at 77 K, UV/VIS diffuse
      reflectance spectroscopy (UV-DRS), scanning electron microscopy (SEM) and
      transmission electron microscopy (TEM).

PMID- 23168908
TI  - Application of a new molecular technique for the genetic evaluation of products
      of conception.
AB  - OBJECTIVES: Karyotyping is a well-established method of investigating the genetic
      content of product of conceptions (POCs). Because of the high rate of culture
      failure and maternal cell contamination, failed results or 46,XX findings are
      often obtained. Different molecular approaches that are not culture dependent
      have been proposed to circumvent these limits. On the basis of the robust
      experience previously obtained with bacterial artificial chromosomes (BACs)-on
      BeadsTM (BoBsTM), we evaluated the same technology that we had used for the
      analysis of prenatal samples on POCs. METHOD: KaryoLiteTM BoBsTM includes 91
      beads, each of which is conjugated with a composite of multiple neighboring BACs
      according to the hg19 assembly. It quantifies proximal and terminal regions of
      each chromosome arm. The study included 376 samples. RESULTS: The failure rate
      was 2%, and reproducibility >99%; false-positive and false-negative rates were
      <1% for non-mosaic aneuploidies and imbalances effecting all three BACs in a
      contig. Detection rate for partial terminal imbalances was 65.5%. The mosaic
      detection threshold was 50%, and the success rate in macerated samples was 87.8%.
      The aneuploidy detection rate in samples with cell growth failure was 27.8%, and
      maternal cell contamination was suspected in 23.1% of 46,XX cultured cells.
      CONCLUSION: KaryoLiteTM BoBsTM as a 'first-tier' test in combination with other
      approaches showed beneficial, cost-effective and clearly enhanced POC testing.

PMID- 23168914
TI  - Effects of citalopram on serotonin neurotransmission.

PMID- 23168916
TI  - Investigation of size-dependent properties of sub-nanometer palladium clusters
      encapsulated within a polyamine dendrimer.
AB  - This study describes the first example of the investigation of electronic,
      geometric, and catalytic properties of Pd subnano metal clusters of Pd(4), Pd(8),
      and Pd(16) stabilized by poly(propylene imine) (PPI) dendrimers using XAFS and IR
      analyses. The relations among these properties are also discussed.

PMID- 23168915
TI  - Nanostructural transformations during the reduction of hollow and porous nickel
      oxide nanoparticles.
AB  - Size-dependent nanostructural transformations occurring during the H(2)-mediated
      reduction of hollow and porous NiO nanoparticles were investigated for controlled
      nanoparticle sizes of ~10 to 100 nm. Transmission electron microscopy reveals
      that the location and number of reduction sites strongly depend on the
      nanoparticle size and structure.

PMID- 23168919
TI  - T-wave normalization during follow-up after early and late mechanical
      recanalization of infarct-related artery with and without stent implantation.
AB  - OBJECTIVE: The aim of this study was to evaluate T-wave normalization during the
      6-month follow-up in the patients who underwent early or late mechanical
      recanalization of the infarct-related artery with and without stent implantation.
      MATERIAL AND METHODS: A total of 248 consecutive patients were divided into the
      following groups: early angioplasty (<=24 hours) without (n=114) or with stents
      (n=6) and late angioplasty (>24 hours) without (n=114) or with stents (n=14). The
      changes in T-wave recovery, QRS score, and echocardiographic left ventricular
      ejection fraction were compared between the groups. RESULTS: At 3 months, a
      greater percentage of patients in the group of early angioplasty with stents had
      again positive T wave than in the group of early angioplasty without stents (75%
      vs. 35%, P=0.05). After 6 months, all patients in the group of early angioplasty
      with stents had again positive T wave. A significant increase in left ventricular
      ejection fraction after 3 months was also observed only in the groups of early
      angioplasty, especially that with stents (30.0% [SD, 3.5%] vs. 38.4% [SD, 5.2%],
      P=0.008). However, there was no significant difference in the QRS score in this
      group comparing the data at discharge and after 3 months (5.4 [SD, 4.3] vs. 5.0
      [SD, 1.9], P>0.05). CONCLUSIONS: The group of early angioplasty with stents
      showed the best recovery of T wave and left ventricular ejection fraction, but
      the QRS score did not change significantly from discharge to the 3-month follow
      up, so the evolution of T wave corresponded to an improvement in ejection
      fraction at follow-up better than the evolution of QRS score.

PMID- 23168920
TI  - Dependence of perceived purity of a chromatic stimulus on saturation adaptation.
AB  - BACKGROUND AND OBJECTIVE: The purpose of sensory adaptation of the visual system
      is to adjust sensitivity of the photoreceptors to optimize the dynamic range of
      response of the visual system. It has been shown in numerous research papers that
      chromatic adaptation influences both color appearance and color discrimination.
      However, there are almost no studies in which the influence of chromatic
      adaptation on perceived purity has been investigated. Therefore, the aim of this
      study was to investigate how chromatic adaptation to stimuli with certain
      saturation influences perceived purity of test stimuli with the same hue but
      different saturation. MATERIAL AND METHODS: As the stimuli were modulated in
      saturation only, we refer to the type of chromatic adaptation used in our study
      as saturation adaptation. Two types of psychophysical methods - the method of
      adjustment and the method of constant stimuli - were used. RESULTS: The results
      obtained with the method of constant stimuli reveal that saturation adaptation
      seems to be nonlinear much the same way as the Bezold-Brucke and the Abney
      effect. In addition, hysteresis of saturation adaptation can be observed in the
      method of adjustment. CONCLUSIONS: Pronounced hysteresis of perceived color
      purity was observed when approaching to the point of subjective equality from the
      side of low saturation of the matching stimulus compared with the side of high
      saturation of the matching stimulus. There was a time course of mechanisms of
      saturation adaptation similar to those of chromatic adaptation previously quoted
      in literature.

PMID- 23168921
TI  - Changes in psychosocial adjustment of adolescent girls in the lessons of physical
      education.
AB  - OBJECTIVE: The aim of the present study was to establish the changes in
      psychosocial adjustment of adolescent girls in the modified lessons of physical
      education. MATERIAL AND METHODS: An experimental design was used in the study.
      The experimental group included 14- to 15-year-old adolescent girls (n=128), and
      the control group comprised adolescent girls of the same school and the same age
      (n=137). The girls of the experimental group participated in modified physical
      education lessons. Once a month, they had a theory class where they received
      knowledge on communication disorders among adolescents and ways of preventing
      them by means of physical activities. In practical classes, the girls of the
      experimental group had sports games (basketball, volleyball, and football),
      enhancing physical abilities, and Pilates exercises. For the estimation of the
      level of adolescents' psychosocial adjustment and its components (self-esteem and
      domination), an adapted questionnaire developed by Rogers and Dymond was applied.
      An adapted questionnaire developed by Huebner was administered to measure
      students' satisfaction with life. RESULTS: The analysis of the data demonstrated
      that when comparing the psychosocial adjustment of the adolescent girls in the
      experimental group before and after the experiment, a significant differences in
      the score of the psychosocial adjustment scale was established (53.81+/-8.34 vs.
      59.41+/-7.66, P<0.05). After the experiment, high life satisfaction was reported
      by 42.19% of the girls (P<0.05). CONCLUSIONS: After the educational experiment,
      the index of the psychosocial adjustment scale in the experimental group improved
      statistically significantly.

PMID- 23168913
TI  - Prevalence of occult hepatitis C virus infection in Iranian patients with
      lymphoproliferative disorders.
AB  - Occult HCV infection is a form of chronic HCV infection characterized by absence
      of detectable anti-HCV antibodies or plasma HCV-RNA but presence of HCV-RNA in
      liver biopsy and/or peripheral blood mononuclear cells (PBMCs). The aim of this
      study was to determine the presence of HCV-RNA in PBMCs of patients with
      lymphoproliferative disorders. One hundred and four consecutive patients with
      lymphoproliferative disorders admitted to Firouzgar Hospital from January 2010 to
      March 2011 were recruited in this cross-sectional study. A 6-ml sample of whole
      blood was taken from the patients, the total RNA was extracted from the samples
      after the separation of plasma and PBMCs. The HCV-RNA of the samples was
      amplified by reverse transcriptase-nested polymerase chain reaction (RT-nested
      PCR). The HCV genotypes of the positive samples were tested using the INNO-LiPATM
      HCV II kit, and the HCV genotypes were then confirmed by sequencing of the 5'-UTR
      fragments after the PCR products were cloned into a pJET1.2/blunt cloning vector.
      The mean age of the patients was 48.3 +/- 1.76 years (range: 16-83). HCV-RNA was
      found in PBMCs from 2 (1.9%) of the 104 patients. Genotyping showed that the
      patients were infected with HCV subtype 1a. One patient suffered non-Hodgkin's
      lymphoma and the other suffered chronic lymphocytic leukemia. Patients with
      lymphoproliferative disorders with negative anti-HCV antibodies and negative
      plasma HCV-RNA may have occult HCV infection. Therefore, in the absence of a
      liver biopsy, the testing of PBMCs for the detection of genomic HCV-RNA may be
      beneficial.

PMID- 23168911
TI  - Omega-3 PUFA ethanolamides DHEA and EPEA induce autophagy through PPARgamma
      activation in MCF-7 breast cancer cells.
AB  - The omega-3 long chain polyunsaturated fatty acids, docosahexaenoic acid (DHA),
      and eicosapentaenoic acid (EPA), elicit anti-proliferative effects in cancer cell
      lines and in animal models. Dietary DHA and EPA can be converted to their
      ethanolamide derivatives, docosahexaenoyl ethanolamine (DHEA), and
      eicosapentaenoyl ethanolamine (EPEA), respectively; however, few studies are
      reported on their anti-cancer activities. Here, we demonstrated that DHEA and
      EPEA were able to reduce cell viability in MCF-7 breast cancer cells whereas they
      did not elicit any effects in MCF-10A non-tumorigenic breast epithelial cells.
      Since DHA and EPA are ligands of peroxisome proliferator-activated receptor gamma
      (PPARgamma), we sought to determine whether PPARgamma may also mediate DHEA and
      EPEA actions. In MCF-7 cells, both compounds enhanced PPARgamma expression,
      stimulated a PPAR response element-dependent transcription as confirmed by the
      increased expression of its target gene PTEN, resulting in the inhibition of AKT
      mTOR pathways. Besides, DHEA and EPEA treatment induced phosphorylation of Bcl-2
      promoting its dissociation from beclin-1 which resulted in autophagy induction.
      We also observed an increase of beclin-1 and microtubule-associated protein 1
      light chain 3 expression along with an enhanced autophagosomes formation as
      revealed by mono-dansyl-cadaverine staining. Finally, we demonstrated the
      involvement of PPARgamma in DHEA- and EPEA-induced autophagy by using siRNA
      technology and a selective inhibitor. In summary, our data show that the two
      omega-3 ethanolamides exert anti-proliferative effects by inducing autophagy in
      breast cancer cells highlighting their potential use as breast cancer preventive
      and/or therapeutic agents.

PMID- 23168917
TI  - Volumetric MRI assessment of brain and spinal cord in Finnish twins discordant
      for multiple sclerosis.
AB  - BACKGROUND AND OBJECTIVE: Brain size, white matter hyperintensity, and the
      development of brain atrophy are known to be highly heritable. The decrease of
      brain volume starts from the very onset of multiple sclerosis and is 10-fold
      compared with normal aging. The aim of this study was to assess whether the brain
      and spinal cord volumes and the volume of white matter lesions differed between
      twins with multiple sclerosis and their asymptomatic co-twins. MATERIAL AND
      METHODS: A co-twin control method was used to evaluate whether the brain and
      spinal cord volumes differ between twins with multiple sclerosis and their co
      twins. Nineteen twin pairs were studied neurologically, and the volumes of T1,
      T2, FLAIR, and gadolinium-enhanced lesions and those of the brain and the spinal
      cord were obtained by magnetic resonance imaging. RESULTS: Significant
      differences in the brain (P=0.064) or spinal cord (P=0.648) volumes were not
      detected. Four of the 7 monozygotic and 5 of the 12 dizygotic co-twins had focal
      brain white matter lesions, but none fulfilled the magnetic resonance imaging
      criteria of Barkhof. Spinal cord lesions were not seen in any of the co-twins.
      CONCLUSIONS: The absence of a significant difference in the brain or spinal cord
      volume between the twins with multiple sclerosis and their co-twins supports the
      recent observation of brain size and the development of brain atrophy being
      highly heritable.

PMID- 23168925
TI  - Salt: important element, invisible menace.
AB  - Public health authorities have mounted campaigns aimed at educating Americans
      about the obesity epidemic and urging them to consume less sugar. Another food
      additive-salt-is also a culprit, and many experts believe it should be the target
      of our next major public health campaign. In addition to obesity, salt is
      associated with increased rates of cardiovascular disease (especially
      hypertension), gastric cancer, and osteoporosis. Most Americans consume much more
      salt than they need or is healthy, with up to 75% of it coming from prepared
      foods. To be successful, these campaigns must educate young consumers. These
      campaigns must also incorporate food manufacturers and change our dining
      environments so that low-sodium foods are accessible and affordable.

PMID- 23168918
TI  - Peripheral blood Th17 cells and neutrophils in Dermatophagoides pteronyssinus
      induced early- and late-phase asthmatic response.
AB  - BACKGROUND AND OBJECTIVE: Biphasic cellular immune reactions, which follow
      allergen inhalation, are a specific feature of inflammation in allergic asthma.
      The aim of this study was to determine the changes in the percentage of
      peripheral blood Th17 cells and neutrophil functions after Dermatophagoides
      pteronyssinus-induced early- and late-phase asthmatic response in patients with
      allergic asthma. MATERIAL AND METHODS: A total of 19 patients with allergic
      asthma were examined. Eleven patients developed an isolated early-phase asthmatic
      response (EAR), whereas 8 developed both early- and late-phase (dual) asthmatic
      responses (DAR) after the bronchial challenge with Dermatophagoides
      pteronyssinus. The control group included 15 healthy subjects. Peripheral blood
      collection was performed 24 hours before as well as 7 and 24 hours after the
      bronchial challenge. The percentage of Th17 cells, and chemotaxis and apoptosis
      of neutrophils were analyzed by flow cytometry. The serum IL-8 and IL-17 levels
      were determined by ELISA. RESULTS: After the bronchial challenge, the percentage
      of Th17 and IL-17 levels increased considerably 7 and 24 hours after the
      challenge in both groups of patients. Moreover, 24 hours after the challenge, the
      percentage of Th17 cells and IL-17 levels were significantly higher in the
      patients with the DAR than those with the EAR or healthy controls. Seven and 24
      hours after the challenge, neutrophil chemotaxis was greater in the patients with
      the DAR as compared with those with the EAR and healthy controls as well. The
      apoptotic activity of neutrophils was lower 24 hours after the challenge in the
      patients with the DAR than those with the EAR. CONCLUSIONS: Dermatophagoides
      pteronyssinus-induced early- and late-phase asthmatic response in patients with
      allergic asthma was found to be accompanied by an increased percentage of
      peripheral blood Th17 cells and elevated serum IL-17 levels as well as altered
      neutrophil functions.

PMID- 23168929
TI  - Assessing and treating hepatic encephalopathy in the older patient.
AB  - Altered mental status (AMS) and confusion are common reasons older patients may
      be admitted to a hospital. Hepatic encephalopathy (HE) is associated with
      confusion and AMS. The following case describes an older male presenting with
      confusion. The patient is treated for both a urinary tract infection and HE. The
      differential diagnosis for AMS is important for pharmacists to understand and
      evaluate to ensure appropriate treatment as well as rule out other medication
      related causes of AMS. Managing patient compliance for the pharmacotherapy
      necessary to treat and prevent HE is particularly important to avoid future
      hospital admissions and complicated placements to an extended-care facility.

PMID- 23168922
TI  - Particulate air pollution and its impact on health in Vilnius and Kaunas.
AB  - Particulate matter in outdoor air has a significant impact on health. Small
      particles, composed of a variety of organic and inorganic compounds, are inhaled
      deep into the respiratory tract. The mechanisms and outcomes are manifold,
      resulting mainly in cardiopulmonary diseases. The current study aimed to quantify
      the health effects of particulate pollutants in Vilnius and Kaunas. MATERIAL AND
      METHODS: For risk estimation, the methodology of health impact assessment was
      employed. The exposure was defined as annual PM(2.5) levels for long-term
      exposure effects and daily PM(10) averages for short-term exposure effects. The
      baseline mortality/morbidity data were retrieved from health registers and
      exposure-response relationships from previous epidemiological studies. For health
      impact calculations, the WHO-developed tool AirQ was also applied. RESULTS: The
      annual average concentration of PM(2.5) was 11 ug/m(3) in Vilnius and 17.5
      ug/m(3) in Kaunas. The exposure above the natural background corresponded
      annually to 263 (95% CI, 68-464) and 338 (95% CI, 86-605) premature deaths in
      Vilnius and Kaunas. This resulted in 3438 (95% CI, 905-5952) and 3693 (95% CI,
      983-6322) years of life lost and in an average decrease in life expectancy of
      0.43 (95% CI, 0.11-0.74) and 0.69 (95% CI, 0.18-1.19) years, respectively. In
      addition, 143 (95% CI, 86-200) and 129 (95% CI, 78-179) respiratory and 297 (95%
      CI, 188-377) and 267 (95% CI, 169-338) cardiovascular hospitalizations per year
      could be expected in Vilnius and Kaunas, respectively. CONCLUSIONS: There is
      substantial exposure to particulate matter in the main Lithuanian cities, which
      causes considerable adverse health effects. Traffic and domestic heating are
      considered locally the most important contributing factors to the degradation of
      air quality.

PMID- 23168923
TI  - Burnout among Lithuanian cardiac surgeons and cardiac anesthesiologists.
AB  - OBJECTIVE: The aim of this study was to determine the prevalence of burnout among
      Lithuanian cardiac surgeons and cardiac anesthesiologists, and associations
      between burnout and the personal and professional characteristics of physicians.
      MATERIAL AND METHODS: A total of 29 cardiac surgeons and 30 cardiac
      anesthesiologists employed in Vilnius and Kaunas university hospitals as well as
      in Klaipeda Hospital were surveyed. Data on personal characteristics (age,
      gender, marital status, number of children, sleeping hours, and addictions),
      professional characteristics (years in practice, work character, work profile,
      and workload), career satisfaction, and symptoms of depression were collected by
      using an anonymous questionnaire. Burnout was measured by the Maslach Burnout
      Inventory-Human Services Survey (MBI-HSS). RESULTS: More than half (54.3%) of the
      physicians surveyed had been in practice for >15 years, 71.2% reported working
      more than 40 hours per week, and 62% reported of being burned out. As much as
      19.3% of physicians reported high emotional exhaustion, 25.9% had high
      depersonalization, and 42.3% demonstrated low personal accomplishment at work.
      Nearly 95% of respondents would become a physician and 82.8% would choose to
      become a cardiac surgeon or a cardiac anesthesiologist again. Physicians who
      worked more than 40 hours per week, smokers, and those who were desperate were
      more likely to be burned out. CONCLUSIONS: Burnout was found to be prevalent
      among Lithuanian cardiac surgeons and cardiac anesthesiologists. Some personal
      and professional characteristics were significantly related to burnout. Burnout
      relief measures should be developed in order to prevent a further increase of
      burnout syndrome among Lithuanian cardiac surgeons and cardiac anesthesiologists.

PMID- 23168928
TI  - Medication therapy management: a challenge for pharmacists.
AB  - While pharmacists have long been delivering personalized clinical patient
      services, recognition of pharmacists as health care providers, realization of the
      value of pharmacist cognitive services, and fair payment for pharmacists have
      been slow to evolve. This article tracks the evolution of medication therapy
      management (MTM) services provided by pharmacists, using the Medicare
      Modernization Act of 2003 as a springboard. The core elements of MTM services are
      discussed and reviewed, and MTM programs and services as outlined in the Medicare
      Part D outpatient prescription drug benefit are thoroughly examined. Pharmacist
      and patient perceptions of the value of MTM are outlined, and barriers to MTM
      implementation at the pharmacy/pharmacist level are evaluated. Key studies
      showing the economic and clinical benefits of MTM services are discussed, as well
      as important drivers that may propel MTM beyond the Medicare Part D threshold.

PMID- 23168926
TI  - Avoiding errors during transitions of care: medication reconciliation.
AB  - When medication errors occur, they often are the result of discrepancies in
      medication information during transitions of care, i.e., moving the patient from
      one setting to another. Pharmacists can play an essential role in performing in
      depth medication reconciliation, which promotes positive patient outcomes and
      decreases health care costs.

PMID- 23168910
TI  - Evidence for possible non-canonical pathway(s) driven early-onset colorectal
      cancer in India.
AB  - Two genetic instability pathways viz. chromosomal instability, driven primarily
      by APC mutation induced deregulated Wnt signaling, and microsatellite instability
      (MSI) caused by mismatch repair (MMR) inactivation, together account for >90% of
      late-onset colorectal cancer (CRC). Our understanding of early-onset sporadic CRC
      is however comparatively limited. In addition, most seminal studies have been
      performed in the western population and analyses of tumorigenesis pathway(s)
      causing CRC in developing nations have been rare. We performed a comparative
      analysis of early and late-onset CRC from India with respect to common genetic
      aberrations including Wnt, KRAS, and p53 (constituting the classical CRC
      progression sequence) in addition to MSI. Our results revealed the absence of Wnt
      and MSI in a significant proportion of early-onset as against late-onset CRC in
      India. In addition, KRAS mutation frequency was significantly lower in early
      onset CRC indicating that a significant proportion of CRC in India may follow
      tumorigenesis pathways distinct from the classical CRC progression sequence. Our
      study has therefore revealed the possible existence of non-canonical
      tumorigenesis pathways in early-onset CRC in India.

PMID- 23168924
TI  - Inherited macular dystrophies and differential diagnostics.
AB  - The inherited macular dystrophies are characterized by different grade central
      visual loss and different character macula atrophy, because of retinal pigment
      epithelium lesion. The cause of photoreceptors degeneration is still not known.
      In this article, we review subjective and objective ophthalmological examines
      essential to diagnosis and differential diagnosis of inherited autosomal dominant
      and autosomal recessive macular dystrophies. It is known seven gene mutations
      (ABCA4, ELOVL4, PROML1, VMD2, Peripherin/RDS, TIMP3, XLRS), which may cause
      inherited macular dystrophies development. Inheritance type of inherited macular
      dystrophies, prevalence, beginning of disease, spread of the disease between
      female and male, clinic, electroretinography, electrooculography, differential
      diagnosis, genetic research and prognosis are also reviewed.

PMID- 23168927
TI  - Measuring adherence in a community-based elderly population.
AB  - OBJECTIVE: To examine the reliability and validity of the Medication Adherence
      Individual Review-Screening Tool (MedAdhIR-ST) for assessing medication adherence
      in a community-dwelling elderly population. DESIGN: A prospective, observational
      pilot study comparing the reliability and validity of the MedAdhIR-ST and the
      Medication Adherence Questionnaire (MAQ). SETTING: Independent senior-housing
      apartments and senior centers in Wake County, North Carolina. PARTICIPANTS:
      Eligible subjects included individuals 60 years of age or older who were living
      in the community and managing their own medication regimens. INTERVENTIONS: Each
      subject was asked to participate in two assessment visits, two weeks (+/- 3 days)
      apart, in which the questions of the MedAdhIR-ST and MAQ were administered. MAIN
      OUTCOME MEASURE: Medication adherence. RESULTS: Both tools showed moderate-to
      high test/retest reliability in the study population (correlation coefficient of
      0.632 for MAQ, and 0.699 for MedAdhIR-ST), and moderate internal consistency
      (Cronbach's a of 0.551 and 0.584, respectively). Moderate concordance in the
      ability to assess adherence was observed between MedAdhIR-ST and MAQ (positive
      correlation coefficient of 0.450). When compared with refill records, MedAdhIR-ST
      was slightly more sensitive (67% vs. 43%) and specific (60% vs. 50%) for
      detecting adherence and nonadherence, respectively, compared with MAQ.
      Exploratory factor analysis indicated that MedAdhIR-ST is multidimensional.
      CONCLUSION: MedAdhIR-ST appears to be a reliable and valid tool for screening
      nonadherence in a community-dwelling elderly population.

PMID- 23168930
TI  - The ins and outs of pharmacy services at a program of all-inclusive care for the
      elderly.
AB  - A program of all-inclusive care for the elderly (PACE) is a medical care model
      currently used in 75 clinical settings across the country. The goal of the model
      is to allow a participant to live independently in the community as an
      alternative to living in a long-term care facility. To be eligible for
      enrollment, participants must meet the following criteria: 55 years of age or
      older, at a nursing-facility level of care (as determined by the state), living
      in the PACE service area, and can be safely cared for in the community at the
      time of enrollment. Once enrolled, care for the participants is provided by an
      interdisciplinary team (IDT) comprising several medical professionals, including
      pharmacists. Although not a required member of the IDT, pharmacists can be
      instrumental to the care of PACE participants. When available, pharmacy services
      can be divided into dispensing pharmacy services--providing onsite access to
      medications--and consultant clinical pharmacy services--providing consultant,
      acute, and chronic disease management, education, administration, and
      academic/scholarly services. With a lack of current pharmacy services at many
      PACE organizations and the potential for expansion of pharmacy services,
      pharmacists can be beneficial for both the IDT and participants in a PACE
      setting.

PMID- 23168932
TI  - Enjoy the holiday season.

PMID- 23168931
TI  - Late profound muscle weakness following heart transplantation due to Danon
      disease.
AB  - INTRODUCTION: Postoperative muscle weakness is a serious complication in surgical
      intensive care patients. It is mostly described as critical illness
      polyneuromyopathy. Risk factors include intensive care length of stay, sepsis,
      poor glycemic control, and combined use of corticosteroids and neuromuscular
      blocking agents, malnutrition, and electrolyte imbalance. METHODS: We report a
      case of late-progressive, profound weakness after heart transplantation for
      noncompaction cardiomyopathy which required prolonged mechanical ventilation. The
      patient's muscle strength recovered completely after prolonged rehabilitation.
      RESULTS: Electromyographic assessment showed myopathy. Muscle biopsy revealed
      Danon disease, a genetic disorder affecting the lysosomal-associated membrane
      protein 2 gene (LAMP2). CONCLUSIONS: The finding of this genetic disorder was
      unexpected, because the preoperative echocardiographic diagnosis of noncompaction
      cardiomyopathy has not been reported in Danon disease. This report underlines the
      need for early availability of pathology results from the explanted heart, which
      showed the same disorder.

PMID- 23168933
TI  - Orthopaedic nurse certification: it's value in patient care.

PMID- 23168936
TI  - Postoperative management of hypoglycemia.
AB  - Individuals with Type 1 and Type 2 diabetes who are managed with insulin are at
      risk for developing hypoglycemia, a significant consequence of insulin therapy.
      Symptoms of hypoglycemia develop rapidly and the condition can be life
      threatening. It is imperative that the inpatient team, including the orthopaedic
      nurse, is able to recognize the signs and symptoms, respond appropriately, and
      prevent hypoglycemia. It is equally important to provide the patient with
      education to prevent, identify, and self-manage hypoglycemia at home. A case
      study example is included that addresses an elderly patient with Type 2 diabetes
      who had a total hip arthroplasty and developed hypoglycemia postoperatively while
      on an orthopaedic unit. Assessment, treatment, prevention, and patient self
      management education of hypoglycemia are reviewed.

PMID- 23168946
TI  - Flexible bronchoscopy outside the hospital setting: to infinity and beyond!

PMID- 23168934
TI  - Enhancing the patient's experience through the total joint replacement continuum
      of care.
AB  - The use of a Total Joint Replacement Pathway provides nurses with a process that
      guides their professional practice. The pathway begins during the preadmission
      phase and follows the patients throughout their hospital stay. Relationship-based
      care is demonstrated by the interdisciplinary care that includes the patient and
      healthcare team. The goal of this article is to describe the continuum of care
      for total joint replacement patients at Stamford Hospital from preadmission to
      discharge. A preoperative class is offered weekly to all patients who are
      scheduled for elective surgery. Approximately 90% of patients attend the
      preoperative classes. This article provides a framework for guiding the clinical
      care of total joint replacement patients. Implementation of this framework will
      ultimately improve patient care and nursing practice in any surgical setting.
      Pain management and patient education are 2 core components of nursing practice
      vital to the success of the Joint Replacement Program and facilitate care of
      these patients through the continuum.

PMID- 23168938
TI  - A retrospective study of the relationship between back pain and unilateral knee
      osteoarthritis in candidates for total knee arthroplasty.
AB  - The purpose of this study was to determine the presence and temporal relationship
      between back pain and knee osteoarthritis (OA). All subjects were candidates for
      unilateral total knee arthroplasty (TKA) to relieve knee pain related to OA, and
      information regarding the prevalence of back pain was collected via
      questionnaires. A total of 42 subjects with unilateral knee OA responded to the
      questionnaires, and 74% of subjects reported chronic back pain, which first
      occurred approximately 10 years before their becoming candidates for TKA. All but
      1 subject reported the onset of back pain prior to TKA candidacy, and less than
      15% of subjects felt that their worst back pain occurred after the onset of knee
      OA. The results of this study are a first step toward quantifying the temporal
      relationship between back pain and unilateral knee OA, and future studies will
      look to assess potential risk factors for knee OA such as strength,
      biomechanical, and anatomical asymmetry.

PMID- 23168940
TI  - A better fit: industry collaboration with nurse-clinicians in the development and
      redesign of a pneumatic compression device.
AB  - BACKGROUND: Intermittent pneumatic compression (IPC) devices offer a safe and
      effective means of thromboprophylaxis but are often uncomfortable, leading to
      poor compliance. METHODS: Two multicenter, prospective trials compared
      traditional IPC sleeves with newly designed IPC sleeves. The primary outcome
      measure was overall patient acceptance. Secondary measures involved nurses'
      impressions, patients' experiences, and device safety. RESULTS: In Trial 1 (n =
      110), 87% of patients preferred the new knee-length sleeve compared with the
      traditional knee-length sleeve. Thigh-length sleeve enrollment was discontinued
      early (n = 38), because nurses reported that the new sleeve did not remain in
      place. Following redesign of the thigh-length sleeve, Trial 2 (n = 110) was
      executed and 82% of patients preferred this sleeve compared with the traditional
      thigh-length sleeve. Patients' experiences and clinicians' impressions were
      better with the new sleeves. No device-related adverse events were reported.
      CONCLUSIONS: Collaboration with nurses yielded a more comfortable IPC sleeve with
      properties that should improve compliance and optimize patient outcomes.

PMID- 23168947
TI  - Complications of Endobronchial Ultrasound-guided Transbronchial Needle
      Aspiration.

PMID- 23168943
TI  - Statins and musculoskeletal pain.

PMID- 23168939
TI  - Surgical site markers:  potential source of infection.
AB  - Observing licensed independent practitioners mark surgical sites with all types
      of marking pens is a concern related to the potential spread of infections from
      patient to patient. The practice of using the same marking pen to mark a surgical
      site has been questioned as a source of cross contamination. A literature review
      was done on recent studies and best practice recommendations to determine whether
      marking pens can act as fomites for nosocomial infections. The review indicated
      that surgical site markers, ink pens, and aging permanent marking pens can be a
      source for cross-infection with methicillin-resistant Staphylococcus aureus,
      other bacteria, fungus, or virus. The type of marking pens used and the act of
      using the same marking pen from patient to patient could contribute to nosocomial
      infections. The literature reviewed recommends a single time use of a surgical
      marking pen. Interventions to prevent cross contamination and postoperative
      surgical site infections are a major concern in the care of the orthopaedic
      patient.

PMID- 23168944
TI  - A call to action from the Chronic Osteoarthritis Management Initiative (COAMI)
      September 2012.

PMID- 23168948
TI  - Performance characteristics of semirigid thoracoscopy in pleural effusions of
      undetermined etiology.
AB  - BACKGROUND: The utility of the recently introduced semirigid thoracoscopy in
      undiagnosed pleural effusions is still unclear. METHODS: A single-center, 4-year
      retrospective analysis of all semirigid medical thoracoscopy procedures was done.
      The diagnostic accuracy of thoracoscopy was calculated as the number of positive
      diagnoses achieved by thoracoscopy in relation to the end-diagnosis achieved in
      the patient group by any means. RESULTS: One hundred fifty procedures were
      analyzed. Ninety-two patients (62.3%) were diagnosed as having a malignant
      disorder, of which mesothelioma was the most common (26%). Pleural thickening and
      nodularity were the most common abnormalities noted. The combined presence of
      nodules and hemorrhagic fluid increased the likelihood of malignancy 9-fold.
      Thirteen patients with a high clinical suspicion of malignancy but negative by
      thoracoscopy underwent mediastinoscopy, computed tomography-guided biopsy, or
      open thoracotomy. A malignant etiology was confirmed in all of them. Overall,
      thoracoscopy provided a diagnostic accuracy of 91.3%, sensitivity of 87%, and
      specificity of 100%. The addition of a second procedure in selected patients
      improved the diagnostic accuracy for malignancy by 8.7%. The procedures were well
      tolerated and only 6 patients developed minor and transient complications such as
      pain, hypoxia, and bradycardia. CONCLUSION: Semirigid thoracoscopy is a safe,
      well-tolerated, and efficacious procedure for establishing the diagnosis in
      pleural effusions of undetermined etiology.

PMID- 23168953
TI  - Prospective pilot trial of dexmedetomidine sedation for awake diagnostic flexible
      bronchoscopy.
AB  - Dexmedetomidine has the favorable properties of sedation, sympatholysis,
      analgesia, and a low risk of apnea. These properties suggest that dexmedetomidine
      may be useful in procedural sedation. In view of this, we conducted a pilot trial
      to determine the feasibility of using dexmedetomidine as a sole agent for
      providing sedation during awake diagnostic flexible bronchoscopy. Patients
      presenting for awake diagnostic flexible bronchoscopy consented to participate in
      a trial of dexmedetomidine sedation for the procedure. In addition to local
      anesthetic topicalization of the airways, dexmedetomidine was infused at 0.5
      MUg/kg over 10 minutes followed by an infusion of 0.2 to 0.7 MUg/kg/h titrating
      to a Ramsay Sedation Scale score of 3. Hemodynamic parameters (heart rate, blood
      pressure), oxygenation status (pulse oximetry), adverse events, use of rescue
      sedation, and patient and proceduralist satisfaction were recorded during the
      trial. Five of 9 recruited patients required rescue sedation to allow the
      procedure to proceed. Dexmedetomidine as a sole agent at an infusion of 0.5
      MUg/kg over 10 minutes followed by an infusion of 0.2 to 0.7 MUg/kg/h is unable
      to provide adequate sedation for awake diagnostic flexible bronchoscopy without
      the need for rescue sedation in a large proportion of patients.

PMID- 23168951
TI  - Feasibility of Applying Real-time Optical Imaging During Bronchoscopic
      Interventions for Central Airway Obstruction.
AB  - BACKGROUND: Interventional bronchoscopists manage central airway obstruction
      (CAO) through dilation, tumor ablation, and/or stent insertion. Anatomical
      optical coherence tomography (aOCT), a validated light-based imaging technique,
      has the unique capacity of providing bronchoscopists with intraprocedural central
      airway measurements. This study aims to describe the potential role of real-time
      aOCT in guiding interventions during CAO procedures. METHODS: Prospective case
      series were recruited from patients referred for bronchoscopic management of
      symptomatic CAO. Preprocedure chest computed tomography (CT) scans were analyzed
      for relevant airway dimensions, such as stenosis caliber and length, and aided
      procedure planning. During bronchoscopy, an aOCT fiberoptic probe was inserted
      through the working channel of the bronchoscope to image the airway stenosis.
      From these aOCT images, stenosis dimensions were measured and compared with the
      preprocedure CT measurements. Preprocedure and postprocedure spirometry, Medical
      Research Council dyspnea score, and Eastern Cooperative Oncology Group
      performance status were collected to assess intervention efficacy. RESULTS:
      Fourteen patients were studied. CT and aOCT-based measurements of airway caliber
      and length correlated closely (r=0.87, P<0.001). Bland-Altman analysis showed
      strong agreement between measurements (mean difference 0.4+/-8.6 mm). The real
      time nature of aOCT imaging provided the advantage of more up-to-date
      measurements where a delay occurred between CT and bronchoscopy or where the
      quality of the CT image was suboptimal. After bronchoscopy, the predicted forced
      expiratory flow in 1 second increased from 67+/-26% to 78+/-19% (P=0.04). Eastern
      Cooperative Oncology Group and dyspnea scores improved in 83% and 75% of the
      patients, respectively. CONCLUSIONS: aOCT provides real-time measurements of
      obstructing central airway lesions that can assist therapeutic interventions such
      as selection of endobronchial stents and airway dilatation procedures.

PMID- 23168949
TI  - Endobronchial Ultrasound-guided Transbronchial Needle Aspiration in a
      Geographical Region With Endemic Histoplasmosis Infection.
AB  - BACKGROUND AND OBJECTIVE: In a geographical area with high prevalence of calcific
      granulomatous inflammation, calcified lymph nodes may affect the diagnostic
      adequacy of endobronchial ultrasound-guided transbronchial needle aspiration
      (EBUS-TBNA). The objective of this study was to describe the diagnostic
      performance of EBUS-TBNA in a region endemic of histoplasmosis related
      granulomatous inflammation. METHODOLOGY: A retrospective review was done for all
      patients referred for EBUS-TBNA over a 7-month period at 2 institutions. Computed
      tomographic (CT) chest studies were reviewed in a blinded manner by 2
      radiologists. In parallel, CT images from 100 unselected sequential control
      patients were reviewed. Cytologic analysis of EBUS-TBNA aspirates was compared
      with a reference standard of definitive pathologic tissue diagnosis or a
      composite of >=6-month clinical follow-up. RESULTS: The prevalence of calcified
      lymph nodes in the 100 control patients was 56%. All 61 patients undergoing EBUS
      TBNA were included. In total, 97 lymph nodes (mean size=13.8 mm) and 7 masses
      were biopsied. Definitive lymph node sampling was achieved in 51 of 61 patients
      (83%). The sensitivity, specificity, and positive and negative predictive values
      of EBUS-TBNA for malignancy (primary lung cancer staging, restaging, and
      reevaluation after cancer therapy, small cell lung cancer, lymphoma, and
      metastatic cancer) were 81%, 100%, 100%, and 84% respectively. On pre-EBUS CT
      chest scan, 60.6% had nodal calcification. The prevalence of cancer was not
      different in those with and without nodal calcification (49%). There was no
      difference in frequency of definitive lymph node sampling in those patients with
      or without nodal calcification. CONCLUSION: In a geographical area with endemic
      histoplasmosis-related nodal calcification, there was no evidence of nodal
      calcification affecting the frequency of EBUS-TBNA definitive lymph node
      sampling.

PMID- 23168950
TI  - Airway wall structure assessed by endobronchial ultrasonography and bronchial
      hyperresponsiveness in patients with asthma.
AB  - BACKGROUND AND OBJECTIVE: The purpose of this study was to evaluate the
      relationship between the wall structure assessed by using endobronchial
      ultrasonography (EBUS) and bronchial hyperresponsiveness in patients with asthma.
      METHODS: Twenty-four patients with stable asthma and 11 individuals without
      asthma were studied. EBUS was performed with a radial 20-MHz ultrasonic probe
      inserted into the intermediate bronchus undergoing flexible bronchoscopy to
      assess the airway wall structure. The percentage of airway wall thickness {WT%;
      defined as [(ideal outer diameter-ideal luminal diameter)/ideal outer
      diameter]*100} was determined by EBUS. We measured bronchial hyperresponsiveness
      to methacholine [the provocative concentration of methacholine causing a decrease
      of 20% or more in forced expiratory volume in 1 s (PC20)]. RESULTS: Percentage
      wall thickness measured by EBUS was significantly greater in patients with asthma
      than that in subjects without asthma (P<0.01). The evaluation of the laminar
      structure using EBUS indicated that the thickness of the second layer in patients
      with asthma was greater than that in subjects without asthma (P<0.05). PC20 was
      negatively correlated with the thickness of the second layer (r=0.52, P<0.01) but
      was not significantly correlated with other layers in patients with asthma.
      CONCLUSIONS: The evaluation of the bronchial mural structure using EBUS might be
      advantageous for assessing the relationship between airway wall remodeling and
      bronchial hyperresponsiveness.

PMID- 23168954
TI  - Sedation With Meperidine for Endobronchial Ultrasound-guided Transbronchial
      Needle Aspiration.
AB  - BACKGROUND: Although endobronchial ultrasound-guided transbronchial needle
      aspiration (EBUS-TBNA) has become increasingly available and more widely used for
      the diagnosis of mediastinal lymph node lesions, there are few reports regarding
      methods of anesthesia. We conducted a retrospective study assessing the efficacy
      of meperidine (MP) for EBUS-TBNA. METHODS: Sixty cases that underwent EBUS-TBNA
      between January 2006 and December 2009 at the Kameda Medical Center were
      retrospectively analyzed. We classified them into 2 groups: cases that were
      performed under sedation with intravenous MP cases (n=31) and cases with general
      anesthesia (GA cases: n=29). Furthermore, we also classified the MP cases into 2
      groups: patients above 65 years of age (elderly patients) and the others (young
      patients) to assess the safety of MP for the elderly. RESULTS: MP of 35 mg was
      administered just before EBUS-TBNA. Mean age, weight, physical status (American
      Society of Anesthesiologists grade), the size of the lesions, and examination
      time were not different between the MP and GA cases. Although the mean number of
      centesis for the MP cases was less than that of the GA cases (2.7 vs. 3.2 times;
      P<0.05), accurate diagnostic rates and sensitivity and specificity of each
      disorder were not different. Although the lowest saturation of peripheral oxygen
      during examination of the MP cases was lower than that of the GA cases (93.6% vs.
      97.6%; P<0.05), GA cases required more vasopressor for a decline in the blood
      pressure than MP cases. Finally, none of the cases had any complications during
      or after the examination. In comparison between the elderly and young patients,
      the physical status, examination time, and the frequency or degree of
      complications were not different either. CONCLUSIONS: EBUS-TBNA under the
      intravenous sedation by MP was as feasible and safe as that under GA. It has a
      possibility to be one of the effective drugs for sedation during EBUS-TBNA
      regardless of age, and we should analyze its safety and efficacy in prospective
      studies henceforth.

PMID- 23168952
TI  - Diagnostic yield of flexible bronchoscopy without fluoroscopic guidance in
      evaluating peripheral lung lesions.
AB  - BACKGROUND AND OBJECTIVES: Flexible bronchoscopy (FB) is frequently performed in
      patients with peripheral lung lesions. The aim of this study was to evaluate the
      diagnostic yield, factors affecting diagnostic yield, complications, and safety
      of FB without fluoroscopic guidance in patients with peripheral lung lesions.
      METHODS: We retrospectively reviewed the medical records of all patients who
      underwent FB without fluoroscopic guidance for the diagnosis of peripheral lung
      lesions between 1999 and 2004. RESULTS: Ninety-three patients were enrolled.
      Among these, 38 lesions were malignant, 46 were benign, and 9 were indeterminate.
      The overall diagnostic rate was 65%, and the diagnostic sensitivities for
      malignant and benign lesions were 68% and 74%, respectively. The diagnostic yield
      was significantly higher for lesions >2 cm (70%) than for lesions <=2 cm (11%; P
      <0.001). The diagnostic yield of transbronchial lung biopsy (46%) was higher than
      that of bronchial washing (29%; P=0.025) or brushing (29%; P=0.022). The yield of
      transbronchial lung biopsy for malignant disease (70%) was higher than that of
      benign disease (35%; P=0.003). Pneumothoraces and significant bleeding developed
      in 4.3% and 2.2% of patients, respectively. CONCLUSIONS: This study showed that
      FB sampling without fluoroscopic guidance was safe with a high rate of accuracy
      for the diagnosis of lung lesions not visible through a bronchoscope. When we
      performed a computed tomography scan and determined the exact location of the
      lesion before FB, the diagnostic yield of FB without fluoroscopic guidance was
      comparable with that reported earlier using fluoroscopy.

PMID- 23168941
TI  - Cervical spine chordoma.

PMID- 23168945
TI  - Multislice cardiac arterial spin labeling using improved myocardial perfusion
      quantification with simultaneously measured blood pool input function.
AB  - PURPOSE: Myocardial blood flow (MBF) is an important indicator of cardiac tissue
      health, which can be measured using arterial spin labeling. This study aimed to
      develop a new method of MBF quantification with blood pool magnetization
      measurement ("bpMBF quantification") that allows multislice cardiac arterial spin
      labeling. THEORY AND METHODS: A multislice segmented ECG-gated Look-Locker T1
      mapping sequence was validated. Quantification of multislice arterial spin
      labeling is not straightforward due to the large volume of blood inverted
      following slice-selective inversion. For bpMBF quantification, a direct
      measurement of the left-ventricle blood pool magnetization was used to
      approximate the blood input function into the Bloch equations. Simulations and in
      vivo measurements in the mouse heart were performed to evaluate the bpMBF method.
      RESULTS: Measurements indicated that blood pool magnetization requires ~3 s to
      return to equilibrium following slice-selective inversion. Simulation and in vivo
      results show that bpMBF quantification is robust to variations in slice-selective
      thickness and therefore applicable to multislice acquisition, whereas traditional
      methods are likely to underestimate multislice perfusion. In vivo, single and
      multislice perfusion values matched well when quantified using bpMBF. CONCLUSION:
      The first multislice cardiac arterial spin labeling technique has been presented,
      which can be used for accurate perfusion measurements in studies of cardiac
      disease.

PMID- 23168955
TI  - Fungal colonization of a pneumonectomy stump.
AB  - A 59-year-old woman developed mild recurring hemoptysis once a week for several
      months after a fall with trauma to the chest. Sixteen years earlier she had
      undergone a right pneumonectomy at a hospital elsewhere for sequelae of pulmonary
      tuberculosis. Bronchoscopy, performed because of the recent hemoptysis, showed
      material in the pneumonectomy stump. The material had a gelatinous appearance,
      green color with a pale margin, and oblique striations. The material was removed
      by grasping with forceps and withdrawing the bronchoscope. Grocott methanamine
      silver stain was positive for septate, nonpigmented fungal organisms. Anatomic
      pathology microscopy also showed mucous, acute inflammatory cells, and necrotic
      tissue. Cytopathology of washings from the bronchial stump showed rare
      degenerated benign bronchial epithelial cells and fungal hyphae. Acid fast
      bacilli smears and cultures were negative. Bacterial cultures showed 3+
      Pseudomonas aeruginosa. The patient had no further hemoptysis.

PMID- 23168956
TI  - Goose-skin Pleura: A Thoracoscopic Finding in a Case of Recurrent Undiagnosed
      Pleural Effusion.
AB  - We present the case of a female patient who presented with undiagnosed pleural
      effusion. Thoracoscopy was performed and at the beginning of the procedure, the
      parietal pleura was rather uniformly congested but with a smooth surface. As time
      passed, the parietal pleura became roughened by bumpy areas of mucosal
      elevations, which looked soft and watery. This became evident during the biopsy
      procedure, as the pleura was markedly edematous. The biopsy specimens were
      nonspecific and the cause of the effusion remained unclear. This phenomenon,
      which we termed "goose-skin" pleura, showed that the origin of the pleural
      effusion formed was the parietal pleura, for unknown causes.

PMID- 23168957
TI  - Mediastinal Infection After Ultrasound-guided Needle Aspiration.
AB  - We describe 2 cases of mediastinal abscess developing after endobronchial
      ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) in patients with
      thoracic malignancies. The first case was that of a 68-year-old male patient with
      a history of colon cancer presenting with new mediastinal adenopathy. EBUS-TBNA
      confirmed metastatic colon adenocarcinoma; however, he developed fever and atrial
      fibrillation 32 days after the procedure and was diagnosed with mediastinal
      abscess. The patient was successfully treated with antibiotics. The second case
      was that of a 66-year-old previously healthy male who presented for evaluation of
      cough. Imaging showed a right paratracheal mass and he underwent EBUS-TBNA
      sampling, which showed malignant cells. Eight days after the procedure the
      patient developed fever and was diagnosed with mediastinal abscess. The second
      patient was treated with antibiotics and several debridements; however, he was
      eventually transitioned to hospice care because of a continued spread of his
      cancer. Although rare, mediastinal infection is a complication of endoscopic
      mediastinal needle aspiration.

PMID- 23168959
TI  - Transmission of Multidrug-resistant Tuberculosis Confirmed by Endobronchial
      Ultrasound Biopsy of a Mediastinal Lymph Node and DNA Fingerprinting Analysis.
AB  - Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) was
      recently introduced for sampling of mediastinal masses and nodes, for staging of
      lung cancer, and for diagnosing other benign diseases including tuberculosis
      (TB). However, EBUS-TBNA has not been used to date to confirm the presence of
      multidrug-resistant TB (MDR-TB). We here describe the diagnosis of MDR-TB of a
      mediastinal lymph node by EBUS biopsy. MDR-TB had been transmitted to our patient
      from her son who had pulmonary TB, and the diagnosis of MDR-TB was confirmed by a
      restriction fragment length polymorphism analysis of the IS6110 segment of
      Mycobacterium tuberculosis isolates. Our findings highlight the use of EBUS-TBNA
      in diagnosing TB, including MDR-TB, and malignancies, in a TB-endemic area.

PMID- 23168964
TI  - Multiple Tracheal Diverticula Detected by Multidetector-row Computed Tomography.
AB  - Multiple tracheal diverticula are rare. We report a case of a 62-year-old man who
      had multiple tracheal diverticula that were detected using multidetector-row
      computed tomography. Axial computed tomography images showed multiple air
      collections contiguous to the trachea. The multiple air collections were visible
      as outpouchings of the parts of the trachea between the cartilages, being located
      almost symmetrically on both lateral sides of the tracheal wall as seen on
      coronal multiplanar reconstruction images. Virtual bronchoscopy confirmed the
      presence of multiple openings in the tracheal wall of the diverticular necks. The
      alteration of the airway was better seen using volume-rendered reconstruction.
      Thin-slice multidetector-row computed tomography and advanced imaging techniques
      may increase the frequency of identification of multiple tracheal diverticula.

PMID- 23168958
TI  - Successful management of subglottic stenosis during the third trimester of
      pregnancy.
AB  - Subglottic stenosis is seldom encountered during pregnancy. Definitive treatment
      is tracheal resection and reanastomosis, although not during the later stages of
      pregnancy. We describe 2 patients who presented during the third trimester of
      pregnancy with significant tracheal obstruction from subglottic stenosis, one
      caused by Wegener granulomatosis and the other idiopathic in nature. Both
      patients refused temporary tracheostomy. We describe the surgical and anesthetic
      management of these patients subsequent to which they were both able to have
      normal, full-term vaginal deliveries.

PMID- 23168960
TI  - The mean green popsicle: using cryotherapy to remove aspirated foreign bodies.
AB  - Foreign body (FB) aspiration can be a life-threatening event. Although more
      common in children, FB aspiration can occur at any age. Symptoms related to FB
      aspiration range from coughing and shortness of breath to asphyxiation. Chest
      imaging can be nonspecific and infrequently identifies an FB. Herein, we describe
      a case of a 54-year-old male patient who aspirated an FB and experienced
      respiratory arrest. He failed to improve with conservative measures and required
      emergent bronchoscopy. He was found to have an FB in his proximal left mainstem
      bronchus that could not be removed using standard bronchoscopy and he was
      referred to our center for definitive care. We used a cryotherapy probe to remove
      the FB. We propose that cryotherapy is a useful tool to remove FBs that are soft
      and amenable to freezing.

PMID- 23168961
TI  - Massive hemorrhage with argon plasma coagulation.
AB  - We report the first case of massive hemorrhage after argon plasma coagulation of
      an endobronchial tumor that obstructed the right main bronchus. This is the first
      report of bleeding complication with argon plasma coagulation while attempting to
      remove the tumor. The patient was successfully resuscitated and discharged
      without sequelae.

PMID- 23168968
TI  - Autofluorescence pattern in tracheobronchopathia osteochondroplastica.

PMID- 23168962
TI  - Tracheal squamous cell carcinoma treated endoscopically.
AB  - Malignant primary tracheal tumors are extremely rare. The most common malignant
      primary tracheal tumors are squamous cell carcinoma and adenoid cystic
      carcinomas. In this brief report, we describe a patient who presented with a
      primary papillary squamous cell carcinoma in-situ at multiple areas in the
      trachea with a significant airway obstruction. Our case was successfully managed
      using a combination of electrocautery and argon photocoagulation for endotracheal
      ablation of the tumor and adjuvant external beam radiotherapy.

PMID- 23168963
TI  - Mycobacterium fortuitum Infection Presenting as Community-acquired Pneumonia in
      an Immunocompetent Host.
AB  - Mycobacterium fortuitum is a rapidly growing environmental mycobacteria,
      frequently isolated from water, dust, and soil, which commonly causes infection
      in the presence of underlying disease or immunosuppression. Skin, soft tissue,
      and bones are important sites of M. fortuitum, but it may colonize in the
      respiratory tract as well. We report the case of an otherwise healthy man who
      presented with signs and symptoms of community-acquired pneumonia. He was
      diagnosed as having primary infection with M. fortuitum and treated with
      multidrug antibacterial therapy. Our case confirms that M. fortuitum poses a
      threat not only to patients with immune defects but also to immunocompetent
      hosts. Flexible bronchoscopy or a transthoracic needle aspiration may be required
      to confirm the diagnosis.

PMID- 23168965
TI  - Mounier-kuhn syndrome: a case report.
AB  - Mounier-Kuhn syndrome is a rare clinical and radiologic entity characterized by
      the pathologic dilatation of the trachea and bronchi. The clinical features
      consist of expiratory central airway collapse, airflow limitation, and clinical
      presentation similar to chronic bronchitis. A 73-year-old man was admitted to the
      hospital with the complaints of cough, sputum, dyspnea, and recurrent bronchitis.
      The radiologic, spirometric, and bronchoscopic findings showed the Mounier-Kuhn
      syndrome. We describe characteristic bronchoscopic and spirometric features of
      the Mounier-Kuhn syndrome.

PMID- 23168966
TI  - Partial duplication of the trachea in an adult: an accidental finding on
      bronchoscopy.
AB  - Partial duplication of the trachea is a very rare congenital tracheal anomaly
      that is detected during infancy. To our knowledge, there are only 3 reported
      cases of partial duplication of the trachea in the literature, which were all
      detected during infancy. We are reporting the first case of partial duplication
      of the trachea in an adult, which was detected accidentally during routine
      diagnostic bronchoscopy. Partial duplication of the trachea can easily be
      misdiagnosed as an accessory bronchus or congenital tracheal diverticulum, if it
      is not carefully evaluated. It is possible that similar cases in the past may
      have been misdiagnosed as tracheal bronchus or congenital tracheal diverticulum
      on bronchoscopy.

PMID- 23168977
TI  - [HIV: which antiretroviral treatment combination should be started?--Initial
      treatment in HIV-infection: still spoilt for choice].

PMID- 23168973
TI  - Re: First-trimester combined screening for trisomy 21 with different combinations
      of placental growth factor, free beta-human chorionic gonadotropin and pregnancy
      associated plasma protein-A. K. O. Kagan, M. Hoopmann, H. Abele, R. Alkier and K.
      Luthgens. Ultrasound Obstet Gynecol  2012; 40: 530-535.

PMID- 23168972
TI  - Re: Accuracy of transvaginal sonography and contrast-enhanced magnetic resonance
      colonography for the presurgical staging of deep infiltrating endometriosis. A.
      Vimercati, M.T. Achilarre, A. Scardapane, F. Lorusso, O. Ceci, G. Mangiatordi, G.
      Angelelli, B. Van Herendael, L. Selvaggi and S. Bettocchi. Ultrasound Obstet
      Gynecol 2012; 40: 592-603.

PMID- 23168975
TI  - Quantitative cervical elastography in pregnancy.

PMID- 23168967
TI  - A key to the large airway!

PMID- 23168981
TI  - [18 year-old woman with recurrent cerebral seizures].

PMID- 23168978
TI  - [Hypertension 2012--still a challenge].

PMID- 23168979
TI  - [Hypertensive emergency with clinical signs of a thrombotic microangiopathy].
AB  - HISTORY AND ADMISSION FINDINGS: A 38-year-old woman presented with strong
      headache, abdominal and chest pain. Blood pressure was 240/115 mmHg. In the
      emergency room lab troponin T was elevated. Further tests showed signs of
      hemolysis and thrombopenia. In addition kidney failure was present.
      INVESTIGATIONS: The ECG showed tachycardia, but no other changes.
      Echocardiography revealed hypertrophy of the left ventricle. In the eye exam
      hypertensive retinopathy was demonstrated. Kidney biopsy showed signs compatible
      with malignant hypertension. TREATMENT AND COURSE: Due to chest pain and
      elevation of troponin T acute coronary syndrome was diagnosed. In combination
      with thrombopenia and hemolysis a thrombotic microangiopathy was suspected.
      Because of the hypertensive emergency malignant hypertension became a possible
      differential diagnosis. Unfortunately antiplatelet treatment precluded kidney
      biopsy right at the beginning. Thus, plasmapheresis was initiated together with
      antihypertensive treatment. Kidney biopsy was done after plasma exchange and
      confirmed the diagnosis of malignant hypertension. CONCLUSION: Diagnosis of
      malignant hypertension can be difficult because symptoms of thrombotic
      microangiopathy are frequently present. In many cases only the combination of
      history, exams of endorgan damage and clinical course is needed to confirm the
      diagnosis. Prompt and sustained lowering of the blood pressure is pivotal. Even
      after successful treatment patients keep an elevated cardiovascular risk and need
      a close follow up.

PMID- 23168980
TI  - [Primay hyperaldosteronism--diagnostic and treatment].
AB  - Primary hyperaldosteronism (PHA) is characterized by an increased Aldosterone
      synthesis which is independent of the Renin-Angiotensin-Aldosterone-System
      (RAAS). The prevalence of PHA in patients who present in specialized hypertension
      centers is approx. 10 %. Besides patients with the classical symptoms known as
      "Conn-Trias" (hypertension, hypokalemia, metabolic alkalosis), the more frequent
      normokalemic patients with PHA also show a worse outcome compared to patients
      with essential hypertension. Identifying these patients is an important task in
      the evaluation of hypertension since targeted treatment options are available.
      Screening for PHA using the Aldosterone-Renin-Ratio (ARR) should be performed in
      patients with hypokalemic, severe or resistant hypertension. In addition, young
      patients with early onset of severe hypertension and/or positive family history
      should be screened. A positive screening result should be followed by a
      confirmatory test. The saline infusion test is the preferred clinical test for
      confirming a suspected PHA since it is accessible and time efficient. Other
      confirmatory tests are not used on a regular basis. After any confirmatory test,
      CT- or MRI-imaging and adrenal vein sampling (AVS) is used in order to
      differentiate between a unilateral adenoma, a bilateral hyperplasia or another
      cause of PHA. CT or MRI usually cannot discriminate smaller tumors form
      hyperplasia. Therefore AVS is used to detect lateralization of autonomous
      aldosterone production. Lateralization of aldosterone production indicates a
      unilateral adenoma. In these cases, laparoscopic adrenalectomy is the therapeutic
      option of choice with a hypertension cure rate of up to 60 %. If no
      lateralization is detectable, bilateral hyperplasia as the underlying cause of
      PHA is likely. Pharmacological inhibition of the mineralocorticoid receptor is
      the preferred treatment option in these cases. If Spironolactone is not well
      tolerated, Eplerenone and potassium-sparing diuretics should be prescribed.
      Often, however, in order to fully control hypertension, additional
      antihypertensive therapy is necessary.

PMID- 23168982
TI  - [Renal denervation in hypertension: when? For whom? And for whom not?].

PMID- 23168985
TI  - [The role of retinal microcirculation in hypertension].

PMID- 23168987
TI  - [Antihypertensive treatment after stroke: target blood pressure and treatment
      recommendations].

PMID- 23168986
TI  - [Revascularization of renal artery stenosis--state of the art].
AB  - Atherosclerotic renal artery stenoses (aRAS) are often associated with an aorto
      iliac type of peripheral occlusive artery disease and may result in deterioration
      of blood pressure control, chronic kidney disease and myocardial dysfunction.
      Stenting of aRAS has almost replaced surgical revascularisation. However, the
      benefit of endovascular treatment of aRAS was challenged by the results of the
      STAR and ASTRAL trials demonstrating similar outcomes for revascularisation and
      conservative treatment. Due to severe limitations in trial design, the study
      results can only be applied to a small proportion of the affected patient
      population. A clinical benefit of renal stenting can only be expected if the
      indication for endovascular procedure was correct, in particular if the
      hemodynamic relevance of the lesion was verified by non-invasive (duplex) or
      invasive (pressure gradient) methods. The known predictors (pulse pressure > 50
      +/- 10 mmHg, high diastolic blood pressure, elevated BNP levels, renal
      insufficiency) for clinical success are often not sufficiently implemented in the
      decision-making process. Unquestioned by international guidelines is the
      indication for revascularisation of aRAS of a single functioning kidneys, severe
      bilateral lesions, resistant hypertension, worsening of renal function, and in
      each kind of severe RAS of non-atherosclerotic nature.

PMID- 23168983
TI  - [Dual blockade of the renin-angiotensin system in hypertensive treatment: yes].

PMID- 23168988
TI  - Training a sophisticated microsurgical technique: interposition of external
      jugular vein graft in the common carotid artery in rats.
AB  - Neointimal hyperplasia is one the primary causes of stenosis in arterialized
      veins that are of great importance in arterial coronary bypass surgery, in
      peripheral arterial bypass surgery as well as in arteriovenous fistulas.(1-5) The
      experimental procedure of vein graft interposition in the common carotid artery
      by using the cuff-technique has been applied in several research projects to
      examine the aetiology of neointimal hyperplasia and therapeutic options to
      address it. (6-8) The cuff prevents vessel anastomotic remodeling and induces
      turbulence within the graft and thereby the development of neointimal
      hyperplasia. Using the superior caval vein graft is an established small-animal
      model for venous arterialization experiment.(9-11) This current protocol refers
      to an established jugular vein graft interposition technique first described by
      Zou et al., (9) as well as others.(12-14) Nevertheless, these cited small animal
      protocols are complicated. To simplify the procedure and to minimize the number
      of experimental animals needed, a detailed operation protocol by video training
      is presented. This video should help the novice surgeon to learn both the cuff
      technique and the vein graft interposition. Hereby, the right external jugular
      vein was grafted in cuff-technique in the common carotid artery of 21 female
      Sprague Dawley rats categorized in three equal groups that were sacrificed on day
      21, 42 and 84, respectively. Notably, no donor animals were needed, because auto
      transplantations were performed. The survival rate was 100 % at the time point of
      sacrifice. In addition, the graft patency rate was 60 % for the first 10 operated
      animals and 82 % for the remaining 11 animals. The blood flow at the time of
      sacrifice was 8+/-3 ml/min. In conclusion, this surgical protocol considerably
      simplifies, optimizes and standardizes this complicated procedure. It gives
      novice surgeons easy, step-by-step instruction, explaining possible pitfalls,
      thereby helping them to gain expertise fast and avoid useless sacrifice of
      experimental animals.

PMID- 23168984
TI  - [Dual blockade of the renin-angiotensin system in hypertensive treatment: no].

PMID- 23168989
TI  - Cerebral blood flow identifies responders to transcranial magnetic stimulation in
      auditory verbal hallucinations.
AB  - Auditory hallucinations comprise a critical domain of psychopathology in
      schizophrenia. Repetitive transcranial magnetic stimulation (TMS) has shown
      promise as an intervention with both positive and negative reports. The aim of
      this study was to test resting-brain perfusion before treatment as a possible
      biological marker of response to repetitive TMS. Twenty-four medicated patients
      underwent resting-brain perfusion magnetic resonance imaging with arterial spin
      labeling (ASL) before 10 days of repetitive TMS treatment. Response was defined
      as a reduction in the hallucination change scale of at least 50%. Responders
      (n=9) were robustly differentiated from nonresponders (n=15) to repetitive TMS by
      the higher regional cerebral blood flow (CBF) in the left superior temporal gyrus
      (STG) (P<0.05, corrected) before treatment. Resting-brain perfusion in the left
      STG predicted the response to repetitive TMS in this study sample, suggesting
      this parameter as a possible bio-marker of response in patients with
      schizophrenia and auditory hallucinations. Being noninvasive and relatively easy
      to use, resting perfusion measurement before treatment might be a clinically
      relevant way to identify possible responders and nonresponders to repetitive TMS.

PMID- 23168991
TI  - Intense physical activity is associated with cognitive performance in the
      elderly.
AB  - Numerous studies have reported positive impacts of physical activity on cognitive
      function. However, the majority of these studies have utilised physical activity
      questionnaires or surveys, thus results may have been influenced by reporting
      biases. Through the objective measurement of routine levels of physical activity
      via actigraphy, we report a significant association between intensity, but not
      volume, of physical activity and cognitive functioning. A cohort of 217
      participants (aged 60-89 years) wore an actigraphy unit for 7 consecutive days
      and underwent comprehensive neuropsychological assessment. The cohort was
      stratified into tertiles based on physical activity intensity. Compared with
      individuals in the lowest tertile of physical activity intensity, those in the
      highest tertile scored 9%, 9%, 6% and 21% higher on the digit span, digit symbol,
      Rey Complex Figure Test (RCFT) copy and Rey Figure Test 30-min recall test,
      respectively. Statistically, participants in the highest tertile of physical
      activity intensity performed significantly better on the following cognitive
      tasks: digit symbol, RCFT copy and verbal fluency test (all P<0.05). The results
      indicate that intensity rather than quantity of physical activity may be more
      important in the association between physical activity and cognitive function.

PMID- 23168997
TI  - The detection of mosaicism by prenatal BoBsTM.
AB  - OBJECTIVE: The objective of the study was to evaluate the ability of a new
      prenatal diagnostic platform - prenatal BACs-on-BeadsTM (BoBsTM) in detecting
      mosaicism by comparison to quantitative fluorescence-polymerase chain reaction
      (QF-PCR). METHODS: A validation study of prenatal BoBsTM was firstly performed
      using 18 artificially constructing mosaic samples involving various aneuploidies
      and microdeletion conditions. Additionally, we compared the accuracy between
      prenatal BoBsTM and QF-PCR for 18 archived clinical mosaic cases and nine
      chromosomally abnormal cell lines with reference to conventional karyotype
      results. RESULTS: In the validation study, BoBsTM allowed the detection of
      mosaicism at a level of 20-40%. Among the clinical mosaic cases, 14/18 cases were
      within the detection of BoBsTM, 8/14 (57.1%) could be identified by BoBsTM and
      6/9 (66.7%) by QF-PCR, but 6/14 (42.9%) were missed by both tests. Three cases
      (16.7%) were detected by prenatal BoBsTM but missed by QF-PCR, whereas QF-PCR
      detected one case that was missed by BoBsTM. The overall sensitivity of BoBsTM in
      detecting mosaicism is 44.4% (8/18), which is slightly higher than that of QF-PCR
      (33.3%; 6/18). CONCLUSION: Prenatal BoBsTM has a sensitivity of 57.1% in the
      detection clinical mosaic cases. According to the validation test, mosaicism of
      20% or greater is detectable by the BoBsTM assay.

PMID- 23168992
TI  - Integrated copy number and gene expression analysis detects a CREB1 association
      with Alzheimer's disease.
AB  - Genetic variation, both single-nucleotide variations and copy number variations
      (CNV), contribute to changes in gene expression. In some cases these variations
      are meaningfully correlated with disease states. We hypothesized that in a
      genetically heterogeneous disorder such as sporadic Alzheimer's disease (AD),
      utilizing gene expression as a quantitative trait and CNVs as a genetic marker
      map within the same individuals in the context of case-control status may
      increase the power to detect relevant loci. Using this approach an 8-kb deletion
      was identified that contains a PAX6-binding site on chr2q33.3 upstream of CREB1
      encoding the cAMP responsive element-binding protein1 transcription factor. The
      association of the CNV to AD was confirmed by a case-control association study
      consisting of the Texas Alzheimer Research and Care Consortium and NIA-LOAD
      Family Study data sets.

PMID- 23168998
TI  - Serum hepatitis B surface antigen is correlated with intrahepatic total HBV DNA
      and cccDNA in treatment-naive patients with chronic hepatitis B but not in
      patients with HBV related hepatocellular carcinoma.
AB  - The aim of the study was to investigate correlations between intrahepatic
      hepatitis B virus total DNA, covalently closed circular DNA (cccDNA), and serum
      HBsAg in treatment-naive chronic hepatitis B and HBV related hepatocellular
      carcinoma (HCC). Liver tissues were taken from 42 HBV related HCC and 36 patients
      with chronic hepatitis B. A fraction of DNA extracted from liver tissue was
      digested with a plasmid-safe ATP-dependent DNase and used for HBV cccDNA
      detection. The remaining DNA was used for the detection of HBV total DNA and beta
      globin, the latter of which is a housekeeping gene and quantified for
      normalization by real-time PCR. Quantitation of serum HBsAg was performed by a
      chemiluminescence assay. Serum HBsAg had positive correlations with serum HBV DNA
      (r = 0.636, P < 0.001), intrahepatic HBV total DNA (r = 0.519, P = 0.001) and
      cccDNA (r = 0.733, P < 0.001) in 36 treatment-naive chronic hepatitis B, while
      HBsAg correlated poorly with DNA (r = 0.224, P = 0.210), intrahepatic total DNA
      and cccDNA in the tumor (r = 0.351, P = 0.031; r = 0.164, P = 0.324,
      respectively) and non-tumor (r = 0.237, P = 0.152; r = 0.072, P = 0.667,
      respectively) liver tissues of 42 HCC. HBV cccDNA and total DNA were
      significantly higher in liver tissue from chronic hepatitis B than in tumor and
      non-tumor of HCC (P < 0.001). Serum HBsAg and HBV DNA were also higher in chronic
      hepatitis B than in HCC (P < 0.001). It was concluded that levels of serum HBsAg
      and intrahepatic cccDNA and total DNA were significantly higher in chronic
      hepatitis B than in HCC, and significant correlations among them were observed in
      treatment-naive chronic hepatitis B but not in HCC.

PMID- 23168999
TI  - Point defect engineering strategies to retard phosphorous diffusion in germanium.
AB  - The diffusion of phosphorous in germanium is very fast, requiring point defect
      engineering strategies to retard it in support of technological application.
      Density functional theory corroborated with hybrid density functional
      calculations are used to investigate the influence of the isovalent codopants tin
      and hafnium in the migration of phosphorous via the vacancy-mediated diffusion
      process. The migration energy barriers for phosphorous are increased
      significantly in the presence of oversized isovalent codopants. Therefore, it is
      proposed that tin and in particular hafnium codoping are efficient point defect
      engineering strategies to retard phosphorous migration.

PMID- 23168994
TI  - Unlocking mechanisms in interleukin-1beta-induced changes in hippocampal
      neurogenesis--a role for GSK-3beta and TLX.
AB  - Glycogen synthase kinase-3beta (GSK-3beta) and the orphan nuclear receptor
      tailless homolog (TLX) are key regulators of hippocampal neurogenesis, which has
      been reported to be dysregulated in both neurodegenerative and psychiatric
      disorders. Inflammation is also implicated in the neuropathology of these
      disorders because of increased levels of the pro-inflammatory cytokine
      interleukin-1beta (IL-1beta) in the brain. At elevated levels, IL-1beta signaling
      through the IL-1 receptor type 1 has been shown to be detrimental to hippocampal
      neurogenesis. TLX is required to maintain neural stem/progenitor cells (NSPCs) in
      an undifferentiated state and is involved in NSPC fate determination, while GSK
      3beta negatively regulates Wnt signaling, a vital pathway promoting neurogenesis.
      This study shows that GSK-3beta inhibition using a small-molecule inhibitor and
      the mood stabilizer lithium restores the IL-1beta-induced decrease in NSPC
      proliferation and neuronal differentiation of embryonic rat hippocampal NSPCs to
      control levels. The IL-1beta-induced effect on NSPCs is paralleled by a decrease
      in TLX expression that can be prevented by GSK-3beta inhibition. The present
      results suggest that GSK-3beta ameliorates the anti-proliferative and pro
      gliogenic effects of IL-1beta, and that TLX is vulnerable to inflammatory insult.
      Strategies to reduce GSK-3beta activity or to increase TLX expression may
      facilitate the restoration of hippocampal neurogenesis in neuroinflammatory
      conditions where neurogenesis is impaired.

PMID- 23169003
TI  - Altruistic cell death and collective drug resistance.

PMID- 23169001
TI  - d(N)/d(S) does not show positive selection drives separation of polar-tropical
      SAR11 populations.

PMID- 23169004
TI  - From selenidostannates to silver-selenidostannate: structural variation of
      chalcogenidometallates synthesized in ionic liquids.
AB  - Presented here are the ionothermal preparation and structural variation of
      selenidostannates, whose structures can be tuned by varying the combination of
      ionic liquids and auxiliary amines as mixed solvent, as well as changing the
      reaction temperature and time. Remarkably, a silver-selenidostannate compound
      featuring lamellar structure was achieved by unusual insertion of linear two
      coordinate Ag(+) ions between the {Sn(3)Se(7)}(n)(2n-) double chains.

PMID- 23168996
TI  - Low vascular endothelial growth factor and interleukin-8 in cerebrospinal fluid
      of suicide attempters.
AB  - A dysregulated immune system influencing pathways for cytokine regulation and
      growth factor expression is implicated in the pathophysiology of several
      neuropsychiatric disorders. Here, we analyzed cerebrospinal fluid (CSF) cytokines
      and growth factors with an ultra-sensitive immunoassay system in 43 medication
      free suicide attempters and 20 healthy male volunteers. CSF vascular endothelial
      growth factor (VEGF) and CSF interleukin-8 (IL-8) levels were significantly lower
      in suicide attempters compared with healthy controls. Further, CSF VEGF showed a
      significant negative correlation with depression severity. CSF IL-6 levels did
      not differ between suicide attempters and healthy controls. Low CSF levels of
      VEGF may represent a lack of trophic support to neurons and downregulation of
      neurogenesis in the hippocampus reflecting more severe depressive states. IL-8
      has also been reported as important in neuroprotection as well as having
      chemokine activity in the innate immune response. The results support a role for
      an impaired innate immunity and dysregulation of neuroprotection in the
      pathophysiology of depression and suicidal behavior.

PMID- 23168995
TI  - Associations between parenting behavior and anxiety in a rodent model and a
      clinical sample: relationship to peripheral BDNF levels.
AB  - Adverse early-life environment is associated with anxiety-like behaviors and
      disorders. Brain-derived neurotrophic factor (BDNF) is sensitive to this
      environment and could be a marker of underlying brain changes. We aimed at
      evaluating the development of anxiety-like behaviors in a rat model of early
      adversity, as well as the possible association with BDNF levels. Similar
      associations were investigated in a sample of adolescent humans. For the rat
      study, Wistar rat litters were divided into: early-life stress (ELS, limited
      access to nesting material) and control groups. Maternal behavior was observed
      from days 1 to 9 of life and, as adults, rats were subjected to behavioral
      testing and BDNF measurements in plasma, hippocampus, amygdala and periaqueductal
      gray. For the human study, 129 adolescents were evaluated for anxiety symptoms
      and perceived parental care. Serum BDNF levels and the Val66Met polymorphism of
      the BDNF gene were investigated. We found that ELS dams showed more pure contact,
      that is, contact with low care and high control, toward pups, and their adult
      offspring demonstrated higher anxiety-like behaviors and plasma BDNF. Also the
      pure contact correlated positively with adult peripheral BDNF. Similarly in
      humans, there was a positive correlation between maternal overprotection and
      serum BDNF only in Met carriers. We also found negative correlations between
      maternal warmth and separation anxiety, social phobia and school phobia. Finally,
      our translational approach revealed that ELS, mediated through variations in
      maternal care, is associated with anxiety in both rats and humans and increased
      peripheral BDNF may be marking these phenomena.

PMID- 23168990
TI  - Progressive loss of cortical gray matter in schizophrenia: a meta-analysis and
      meta-regression of longitudinal MRI studies.
AB  - Cortical gray matter deficits have been found in patients with schizophrenia,
      with evidence of progression over time. The aim of this study was to determine
      the extent of progressive cortical gray matter volume changes over time in
      schizophrenia, their site and time of occurrence, and the role of potential
      moderators of brain changes. English language articles published between 1
      January 1983 and 31 March 2012 in the MEDLINE and EMBASE databases were searched.
      Longitudinal magnetic resonance imaging studies comparing changes in cortical
      gray matter volume over time between patients with schizophrenia and healthy
      controls were included. Hedges g was calculated for each study. Analyses were
      performed using fixed- and random-effects models. A subgroup analysis was run to
      explore the pattern of brain changes in patients with first-episode
      schizophrenia. A meta-regression statistic was adopted to investigate the role of
      potential moderators of the effect sizes (ESs). A total of 19 studies, analyzing
      813 patients with schizophrenia and 718 healthy controls, were included. Over
      time, patients with schizophrenia showed a significantly higher volume loss of
      total cortical gray matter, left superior temporal gyrus (STG), left anterior
      STG, left Heschl gyrus, left planum temporale and posterior STG bilaterally. Meta
      analysis of first-episode schizophrenic patients showed a more significant
      pattern of progressive loss of whole cerebral gray matter volume involving the
      frontal, temporal and parietal lobes, and left Heschl gyrus compared with healthy
      controls. Clinical, pharmacologic and neuroradiological variables were found to
      be significant moderators of brain volume changes in patients with schizophrenia.
      The meta-analysis demonstrates that progressive cortical gray matter changes in
      schizophrenia occur with regional and temporal specificity. The underlying
      pathological process appears to be especially active in the first stages of the
      disease, affects the left hemisphere and the superior temporal structures more
      and is at least partly moderated by the type of pharmacological treatment
      received.

PMID- 23169000
TI  - PLAU inferred from a correlation network is critical for suppressor function of
      regulatory T cells.
AB  - Human FOXP3(+)CD25(+)CD4(+) regulatory T cells (Tregs) are essential to the
      maintenance of immune homeostasis. Several genes are known to be important for
      murine Tregs, but for human Tregs the genes and underlying molecular networks
      controlling the suppressor function still largely remain unclear. Here, we
      describe a strategy to identify the key genes directly from an undirected
      correlation network which we reconstruct from a very high time-resolution (HTR)
      transcriptome during the activation of human Tregs/CD4(+) T-effector cells. We
      show that a predicted top-ranked new key gene PLAU (the plasminogen activator
      urokinase) is important for the suppressor function of both human and murine
      Tregs. Further analysis unveils that PLAU is particularly important for memory
      Tregs and that PLAU mediates Treg suppressor function via STAT5 and ERK signaling
      pathways. Our study demonstrates the potential for identifying novel key genes
      for complex dynamic biological processes using a network strategy based on HTR
      data, and reveals a critical role for PLAU in Treg suppressor function.

PMID- 23169011
TI  - Murder of the Chest X-ray.

PMID- 23169009
TI  - Our troubled colleagues.

PMID- 23169008
TI  - Newborn brachial plexus palsy: evaluation of severity using quantitative
      ultrasound of muscle.
AB  - INTRODUCTION: We studied ultrasound features of muscle after nerve injury.
      METHODS: We evaluated ultrasound measurements of muscle thickness and backscatter
      in injured and contralateral uninjured elbow flexors of 51 children with newborn
      brachial plexus palsy (NBPP) and compared the results to elbow flexor function
      (Active Movement Scale), defined as normal, moderate, or severe. RESULTS:
      Compared with uninjured limbs, muscle in injured arms was 15% thinner with severe
      impairment, 17% thicker with moderate impairment, and no different with normal
      function. Relative to uninjured limbs, moderately impaired muscle was thicker
      than both severely impaired and normal strength muscle. Backscatter was higher in
      injured than in uninjured limbs regardless of function. In 17 patients with
      sequential measures, muscle thickness, but not backscatter, increased with
      function over time. CONCLUSIONS: Muscle thickness differentiates moderate from
      severe impairment after NBPP and increases with recovery over time. Muscle
      backscatter identifies prior injury regardless of function.

PMID- 23169012
TI  - The new application and match system for interventional pulmonology fellowships.

PMID- 23169002
TI  - Programming stress-induced altruistic death in engineered bacteria.
AB  - Programmed death is often associated with a bacterial stress response. This
      behavior appears paradoxical, as it offers no benefit to the individual. This
      paradox can be explained if the death is 'altruistic': the killing of some cells
      can benefit the survivors through release of 'public goods'. However, the
      conditions where bacterial programmed death becomes advantageous have not been
      unambiguously demonstrated experimentally. Here, we determined such conditions by
      engineering tunable, stress-induced altruistic death in the bacterium Escherichia
      coli. Using a mathematical model, we predicted the existence of an optimal
      programmed death rate that maximizes population growth under stress. We further
      predicted that altruistic death could generate the 'Eagle effect', a counter
      intuitive phenomenon where bacteria appear to grow better when treated with
      higher antibiotic concentrations. In support of these modeling insights, we
      experimentally demonstrated both the optimality in programmed death rate and the
      Eagle effect using our engineered system. Our findings fill a critical conceptual
      gap in the analysis of the evolution of bacterial programmed death, and have
      implications for a design of antibiotic treatment.

PMID- 23169016
TI  - Virtual reality simulation of basic pulmonary procedures.
AB  - BACKGROUND: Virtual reality (VR) bronchoscopy simulators have been available for
      more than a decade, and have been recognized as an important aid in bronchoscopy
      training. The existing literature has only examined the role of VR simulators in
      diagnostic bronchoscopy. The aim of this study was to find out whether the
      simulations of both diagnostic bronchoscopies and more advanced procedures were
      realistic, and whether clinical experience in bronchoscopy was associated with
      better and faster performance of basic pulmonary procedures in the simulator.
      METHODS: Thirty physicians performed 8 procedures, each on a VR bronchoscopy
      simulator. They performed 3 diagnostic bronchoscopies, 2 bronchoalveolar lavages,
      and 3 procedures in which they used all the available biopsy tools (needle,
      brush, and forceps) that could be used for tumors of increasing procedural
      difficulty. After the procedures, the physicians answered a questionnaire
      regarding the realism of the simulator. RESULTS: The realism of the anatomy and
      the appearance of the scope were rated higher than the movement of the scope,
      feeling of resistance, and performances of bronchoalveolar lavages and biopsies.
      Overall, the simulator was judged to be realistic and all the physicians agreed
      that VR bronchoscopy simulation is a good way to learn bronchoscopy. The more
      experienced physicians performed faster than the less experienced physicians. The
      simulator feedback did not allow for an assessment of the quality of the
      performed biopsies. CONCLUSIONS: Simulation of performing the procedures was
      significantly less realistic than the simulation of the anatomy and the scope. It
      was impossible to use the simulator metrics to assess the quality of the
      biopsies. Despite these deficiencies, clinicians recommend the use of VR
      simulators in the teaching of pulmonary procedures.

PMID- 23169017
TI  - Bronchoscopy findings in children with recurrent and chronic stridor.
AB  - BACKGROUND: To describe the bronchoscopic findings and treatment decision of
      children with chronic or recurrent stridor referred to the pediatric respiratory
      clinic at Queen Rania Hospital for Children. METHODS: All children who underwent
      flexible bronchoscopy at the pediatric bronchoscopy unit for chronic stridor from
      January 2009 to January 2010 were included. Stridor was divided into 3 groups:
      inspiratory, expiratory, or biphasic. All patients from 2 weeks of age till 14
      years were included. Files of these patients were retrospectively reviewed. A
      specially formulated data sheet including clinical history and physical findings,
      type of stridor, bronchoscopic findings, and management decision was used.
      Radiologic investigation results were included when relevant. Flexible
      bronchoscopy was performed under sedation and topical anesthesia. RESULTS: A
      total of 64 children [35 (54.7%) male and 29 (45.3%) female] were included.
      Twenty-four patients had inspiratory stridor. There were 33 patients with
      biphasic stridor (subglottic stenosis in 9, paradoxical vocal cord movement in 6,
      vascular ring in 5, subglottic hemangioma in 3, vocal cord paralyses in 4,
      foreign body in 2, laryngeal web in 2, and absent vocal cord and tracheal
      bronchus in 1 each). Seven children had expiratory stridor. Of patients with
      laryngomalacia, 50% had associated tracheomalacia and 70% of those with
      laryngomalacia and all patients with tracheomalacia had associated
      gastroesophageal reflux. Two patients with paradoxical vocal cord movement were
      found to have Arnold-Chiari malformation. All patients with vascular rings
      underwent surgery. CONCLUSION: Flexible bronchoscopy should be performed in all
      patients with chronic or recurrent stridor to assess the airway and guide further
      investigations and management.

PMID- 23169014
TI  - Bronchoscopic fibered confocal fluorescence microscopy image characteristics and
      pathologic correlations.
AB  - BACKGROUND: Fibered confocal fluorescence microscopy (FCFM) is a new imaging
      modality in bronchoscopy. The purpose of this study was to assess FCFM
      reliability, interpretation, and to make image-pathologic correlations. METHODS:
      Twenty-six patients underwent FCFM. A validation set was used to determine image
      characteristics and interobserver reliability. Each patient underwent
      bronchoscopy using a standardized protocol. The images were evaluated by 4
      observers based on brightness, fiber thickness, and alveolar cellularity. Image
      characteristics showing good interobserver agreement were tested to see if they
      were related to smoking status. Subsequently, 18 consecutive patients underwent
      FCFM and biopsy to correlate images with pathology. The blinded reviewers were
      asked to distinguish between controls and patients with pathologically proven
      disease. RESULTS: Interobserver agreement for image brightness, as measured by
      intraclass correlation coefficients (ICCs), ranged from 0.48 to 0.92 (P<0.001)
      and varied by location. ICCs for image brightness were high, ranging from 0.53 to
      0.99 (P<0.001). Agreement for fiber thickness was poor for respiratory
      bronchioles (ICC 0.12, P<0.05) and fair for alveoli (ICC range, 0.37 to 0.42,
      P<0.001). The intraobserver (ICC range, 0.69 to 0.91, P<0.001) and intrapatient
      (ICC 0.65 to 0.84, P<0.001) reliability were excellent. Computer image
      interpretation showed excellent agreement with humans (ICC 0.62 to 0.99,
      P<0.001). Smoking was inversely associated with respiratory bronchiole brightness
      (P<0.001). In FCFM-pathologic correlation, FCFM could distinguish normal from
      diseased tissue; however, specific diseases could not be distinguished from other
      diseases. CONCLUSION: FCFM shows a high degree of image reliability and can
      detect changes in the respiratory bronchioles because of smoking and other
      diseases, but whether it can discriminate among diseases requires additional
      study.

PMID- 23169005
TI  - Association of VEGF and KDR single nucleotide polymorphisms with colorectal
      cancer susceptibility in Koreans.
AB  - Vascular endothelial growth factor (VEGF) and its receptor kinase insert domain
      containing receptor (KDR) play crucial roles in angiogenesis, which contributes
      to the development and progression of solid tumors. The aim of this study was to
      investigate the associations of VEGF (-2578C > A, -1154G > A, -634G > C, and 936C
      > T) and KDR (-604T > C and 1192G > A) polymorphisms with the development of
      colorectal cancer (CRC). A total of 882 participants (390 CRC patients and 492
      controls) were enrolled in the study. The genotyping of VEGF and KDR
      polymorphisms was performed by polymerase chain reaction-restriction fragment
      length polymorphism assay. We found that the CT and TT genotype of the 936C > T
      was associated with an increased risk of CRC compared with the CC genotype as the
      dominant model for the T allele. In addition, we also found a increased CRC risk
      with TC + CC genotype of KDR -604T > C compared with TT genotype in CRC patients
      and control subjects. Similarly, KDR 1192G > A also showed significant
      association between 1192G > A variants and risk of CRC. In the haplotype
      analyses, haplotype -2578A/-1154A/-634G/936T of VEGF polymorphisms and haplotype 
      604C/1192G and -604C/1192A of KDR polymorphisms were associated with an increased
      susceptibility of CRC. Our results suggest that the VEGF 936C > T, KDR -604T > C,
      and KDR 1192G > A polymorphisms may be contribute to CRC risk in the Korean
      population.

PMID- 23169015
TI  - Endoscopic removal of metallic airway stents.
AB  - BACKGROUND: Metallic airway stents must be removed when stent-related
      complications cause airway injury or obstruction. This study compared the
      techniques and complications associated with endoscopic removal of covered
      metallic stents (CMSs) and uncovered metallic stents (UCMS). METHODS: A
      retrospective analysis of data from 48 patients with airway disorders treated
      with 40 CMSs and 18 UCMSs, in whom endoscopic stent removal was indicated between
      January 2005 and January 2010 was carried out. Procedures were performed under
      general anesthesia with a rigid bronchoscope or local anesthesia with a flexible
      bronchoscope. The airway wall of 54 stents was pretreated with argon plasma
      coagulation and/or cryoablation before stent removal. Balloon dilation, argon
      plasma coagulation, CO2 cryoablation, or chemotherapy was performed to prevent
      restenoses after the stent removal in selected patients. RESULTS: Of the stents,
      84.5% (49 of 58) were eventually removed, including 36 CMSs and 13 UCMSs; 4 CMSs
      and 5 UCMSs could not be removed. Strut fracture was more common in UCMSs (77.8%)
      than in CMSs (5%; P<0.001). Of patients with CMS, 91.7% underwent successful
      removal of intact stents, whereas 92.3% of patients with UCMS were removed
      damaged or piecemeal. In CMS or UCMS, major complications of stent removal
      included mucosal tear with bleeding and unveiling of significant granulation
      tissue from behind the stent. No deaths occurred during the procedure.
      CONCLUSIONS: CMSs can be effectively and safely removed by a flexible
      bronchoscope with a retrieval hook without major sequelae, whereas UCMSs are very
      difficult to remove, and complications are very common. Metallic stents should be
      used only as a last resort in patients with airway disorders.

PMID- 23169018
TI  - Lymphangioleiomyomytosis: Are the Findings of Video-assisted Thoracoscopy
      Pathognomonic?
AB  - A 22-year-old African American female patient presented with a sudden onset of
      difficulty in breathing for approximately 2 days accompanied by bilateral
      pleuritic chest pain. Her past medical history was significant for tuberous
      sclerosis and mental retardation. Preliminary radiographic imaging showed
      bilateral pneumothoraces for which bilateral chest tubes were subsequently
      inserted. A computed tomography scan of the chest showed cystic changes
      compatible with lymphangioleiomyomytosis (LAM). She underwent a video-assisted
      thoracoscopy with pleurodesis and an open lung biopsy for the confirmation of the
      diagnosis. Cystic changes involving the visceral pleura were noticed during the
      procedure. Understanding that "tuberous sclerosis complex" is an illness that
      could be associated with LAM should prompt clinicians to consider the diagnosis
      if the patients present with shortness of breath, pneumothorax, diffuse cystic
      lung changes, or hemoptysis. Hemoptysis results from pulmonary venous
      hypertension, which is a consequence of LAM. Pleuroscopy or video-assisted
      thoracoscopy may show unusual findings, as described in this case, which could be
      pathognomonic for the diagnosis.

PMID- 23169006
TI  - Chronic exposure to stress hormones alters the subtype of store-operated channels
      expressed in H19-7 hippocampal neuronal cells.
AB  - Differentiating H19-7 hippocampal precursor cells up-regulate (~4.3-fold) store
      operated channel (SOC) activity; relatively linear current-voltage curves
      indicate an I(SOC) subtype of SOC. In differentiated H19-7 neurons, the majority
      of agonist (arginine vasopressin, AVP)-stimulated Ca(2+) entry occurs via SOCs,
      based on 2-aminoethyldiphenylborinate (2-APB) inhibition data and the observation
      that transient receptor potential C1 (TRPC1) channel knock down cells show a
      dramatic reduction of thapsigargin-stimulated store-operated Ca(2+) entry (SOCE)
      and inhibition of AVP-stimulated Ca(2+) entry. Treatment of H19-7 cells with the
      rat stress hormone corticosterone during differentiation induces a significant
      increase in AVP-stimulated Ca(2+) entry, which is virtually eliminated by 2-APB,
      suggesting a corticosterone-induced increase of SOCE. Corticosterone also
      enhances AVP-stimulated Mn(2+) entry, confirming an elevated Ca(2+) entry
      pathway, rather than a decreased Ca(2+) extrusion. When corticosterone addition
      is delayed until after H19-7 cells have fully differentiated, it still elevates
      SOCE. In corticosterone-treated H19-7 cells, the knock down of TRPC1 no longer
      blocks thapsigargin-stimulated Ca(2+) entry suggesting that the subtype of SOCs
      expressed in H19-7 cells is altered by corticosterone treatment.
      Electrophysiological studies demonstrate that store-operated currents in
      corticosterone-treated H19-7 cells exhibit a highly inward rectifying current
      voltage curve consistent with an I(CRAC) subtype of SOCs. Consistent with this
      finding is the observation that corticosterone treatment of H19-7 cells increases
      the expression of the I(CRAC) channel subunit Orai1. Thus, the subtype of SOCs
      expressed in H19-7 hippocampal neurons can be altered from I(SOC) to I(CRAC) by
      chronic treatment with stress hormones.

PMID- 23169007
TI  - IL-33 citrine reporter mice reveal the temporal and spatial expression of IL-33
      during allergic lung inflammation.
AB  - Interleukin-33 (IL-33) is an IL-1 family cytokine that signals via its receptor
      T1/ST2, and is a key regulator of inflammation, notably the type-2 response
      implicated in allergic asthma. Critical to our understanding of the role of IL-33
      is the identification of the cellular sources of IL-33. Although progress has
      been made in this area, the development of a robust live cell reporter of
      expression would allow the localisation of IL-33 during ongoing immune responses.
      We have generated a fluorescent reporter mouse line, Il33(Cit/+), to define the
      expression profile of IL-33 in vivo and demonstrate its temporal and spatial
      expression during experimental allergic asthma responses. We found that type-2
      pneumocytes constitute the major source of IL-33 upon allergic lung inflammation
      following exposure to OVA, fungal extract or ragweed pollen. Using Il33(Cit/Cit)
      mice (IL-33-deficient), we establish a role for IL-33 early in the initiation of
      type-2 responses and the induction of nuocytes (ILC2). We also demonstrate a
      potential mechanism of action by which IL-33 rapidly initiates type-2 immune
      responses. Il33(Cit/+) mice have enabled new insights into the initiation of type
      2 responses and will provide an important tool for further dissection of this
      important inflammatory pathway in vivo.

PMID- 23169019
TI  - Cough-induced Tracheobronchial Mucosal Bleeding.
AB  - A 56-year-old man presented with moderate hemoptysis. It was preceded by a severe
      bout of cough. Flexible bronchoscopy showed diffuse tracheobronchial mucosal
      petechiae and bleeding. The patient was not suffering with any coagulopathies. He
      did not receive antiplatelet drugs. Hemoptysis resolved with cough suppressant.
      Subsequent bronchoscopy revealed the complete resolution of petechiae. The
      mechanism of bleeding after the bout of coughing is discussed.

PMID- 23169010
TI  - Kinetic modeling of hyperpolarized (13)C pyruvate metabolism in tumors using a
      measured arterial input function.
AB  - Mathematical models are required to estimate kinetic parameters of [1-(13)C]
      pyruvate-lactate interconversion from magnetic resonance spectroscopy data. One-
      or two-way exchange models utilizing a hypothetical approximation to the true
      arterial input function (AIF), (e.g. an ideal 'box-car' function) have been used
      previously. We present a method for direct measurement of the AIF in the rat. The
      hyperpolarized [1-(13)C] pyruvate signal was measured in arterial blood as it was
      continuously withdrawn through a small chamber. The measured signal was corrected
      for T1 relaxation of pyruvate, RF pulses and dispersion of blood in the chamber
      to allow for the estimation of the direct AIF. Using direct AIF, rather than the
      commonly used box-car AIF, provided realistic estimates of the rate constant of
      conversion of pyruvate to lactate, kpl, the rate constant of conversion of
      lactate to pyruvate klp, the clearance rate constant of pyruvate from blood to
      tissue, Kip, and the relaxation rate of lactate T1la. Since no lactate signal was
      present in blood, it was possible to use a simple precursor-product relationship,
      with the tumor tissue pyruvate time-course as the input for the lactate time
      course. This provided a robust estimate of kpl, similar to that obtained using a
      directly measured AIF.

PMID- 23169013
TI  - FDG Uptake and the Diagnostic Yield of Transbronchial Needle Aspiration.
AB  - OBJECTIVE: The objective of our study was to investigate whether
      fluorodeoxyglucose (FDG) positron emission tomography scanning uptake impacts the
      yield of transbronchial needle aspiration (TBNA). METHODS: We carried out a
      retrospective analysis of data from 140 consecutive patients (178 lymph nodes)
      undergoing positron emission tomography-computed tomography scanning and
      subsequent TBNA with rapid onsite cytologic evaluation of the specimen. Patient
      and lymph node characteristics, including nodal station, size, FDG uptake, number
      of passes with the needle, sample adequacy, and the final diagnosis were
      recorded. RESULTS: The diagnostic yield of TBNA was 75%. Themean short axis lymph
      node diameter was 18.7+/-9 mm and mean maximum standardized uptake value (SUVmax)
      was 7.7+/-4. The diagnostic yield depended on the lymph node size [odds ratio
      (OR)=1.07 (1.00-1.14); P=0.04], clinical suspicion of malignancy [OR=5.13 (1.95
      13.52); P=0.001], malignant diagnosis [OR=4.91 (1.71-14.09); P=0.003], and FDG
      uptake [for SUVmax cutoff of 3.0: OR=33.8 (9.2-124); P<0.001]. Only clinical
      suspicion of cancer [OR=6.2 (2.2-17.2); P=0.001] and FDG uptake [for SUVmax
      cutoff of 3.0: OR=33.8 (9.2-123.8); P<0.001] remained significant on multivariate
      analysis. Receiver operating characteristic curves combining 3 key variables
      (lymph node size, clinical suspicion of malignancy, and SUVmax) showed an area of
      0.83 under the curve for a 2.5 SUVmax cutoff and 0.84 for a 3.0 cutoff.
      CONCLUSIONS: FDG uptake is the single most important variable impacting the TBNA
      yield. TBNA of lymph nodes with an SUVmax less than 3.0 is rarely diagnostic.

PMID- 23169020
TI  - Bronchoscopic application of mitomycin-C as adjuvant treatment for benign airway
      stenosis.

PMID- 23169021
TI  - Sequential bronchoscopy in the management of lobar atelectasis secondary to
      allergic bronchopulmonary aspergillosis.
AB  - Lobar atelectasis is a common complication in patients with cystic fibrosis.
      Failure to reexpand the lung isassociated with poorer outcomes. We report
      sequential weekly flexible bronchoscopy, with instillation of recombinant human
      DNase, in 5 patients with cystic fibrosis who had lobar collapse secondary to
      allergic bronchopulmonary aspergillosis. The number of procedures ranged from 2
      procedures in 3 patients, 3procedures in 1 patient, and 4 procedures in another
      patient. All the patients achieved full reexpansion radiologically and the
      procedures were well tolerated. We conclude that sequential bronchoscopy in
      patients who fail to show reexpansion of the lung is effective and should be
      considered as part of standard medical management.

PMID- 23169022
TI  - Bronchoscopic diagnosis of a ruptured hydatid cyst in a young male with
      hemoptysis.
AB  - An 18-year-old male patient, earlier diagnosed to have a right lung lesion,
      presented with mild, sudden onset of hemoptysis and chest discomfort. The
      patient's radiograph showed a consolidated area in the right upper lobe with a
      significant reduction in the size compared with the size 5 years earlier.
      Computerized tomography of the chest showed a ruptured cystic lesion in the right
      upper lobe. Bronchoscopy showed gelatinous, white membrane-like structures
      extruding from the anterior segmental bronchus of the right upper lobe bronchus.
      The membranes were sucked out partially, and histologic examination showed
      laminated membranes of a hydatid cyst. The cyst was subsequently removed
      surgically. Bronchoscopy can be a valuable aid in the diagnosis of a ruptured
      hydatid cyst of the lung.

PMID- 23169023
TI  - Pleuroparenchymal fibroelastosis presenting as a hypermetabolic lung nodule.
AB  - Idiopathic pleuroparenchymal fibroelastosis is a rare, benign entity consisting
      of fibrotic thickening of the pleura and subpleural parenchyma due to elastic
      fiber proliferation. We present an elderly, male smoker with chronic obstructive
      airway disease and bilateral apical pleuropulmonary fibrotic changes. The
      computed tomogram of the chest showed a spiculated nodule in the left upper lobe
      and chronic fibrotic nodular changes in the right lung. A positron emission
      tomographic (PET) scan with 18-fluorodeoxyglucose-PET showed a hypermetabolic
      nodule in the left upper lobe and uptake by the left axillary lymph nodes.
      Surgical resection of the nodule for presumptive malignancy showed fibroelastosis
      with reactive lymph node hyperplasia. To our knowledge, this is the first
      reported case of nodular parenchymal fibroelastosis, with increased uptake as
      shown on a PET scan.

PMID- 23169024
TI  - Role of fiberoptic bronchoscopy in intensive care unit: current practice.
AB  - Since its introduction in daily medical practice in the late 20th century,
      flexible bronchoscopy has had an increasing role in the everyday life of the
      pulmonologist. Not only for diagnosis, but also for therapeutic interventions, it
      has achieved widespread use and is now performed in a diversity of clinical
      scenarios. For several reasons, from easy performance in trained hands to
      versatility, diagnostic reliability, and safety, flexible bronchoscopy is now
      widely accepted and increasingly used in the management of critically ill
      patients. The knowledge of the unique features of intensive care unit patients,
      as well as indications and contraindications for the procedure, is paramount in
      achieving optimal results, while minimizing potential risks and complications.
      Performing bronchoscopy in an unstable patient, often on mechanical ventilation,
      requires awareness of the specific pathophysiological impact of the procedure.
      This in turn determines respiratory and cardiovascular derangements frequently
      observed during the procedure. This article reviews indications, pathophysiology,
      technical aspects, complications, and contraindications of flexible bronchoscopy
      in the critical care patient.

PMID- 23169025
TI  - Endobronchial ultrasonography and magnetic resonance imaging in tracheobronchial
      stenosis from ulcerative colitis.
AB  - A 49-year-old woman presented with continuous cough, progressive dyspnea on
      exertion, and hoarseness. She had a total colectomy for ulcerative colitis 17
      years earlier. Bronchoscopy showed circumferential mucosal erythema. The surface
      of the tracheal mucosa was irregular and bled easily on contact. Endobronchial
      ultrasonography and magnetic resonance imaging (MRI) showed characteristic
      findings that suggested that the lesion was located within the tracheal mucosa
      and submucosa. Endobronchial ultrasonography images showed circumferential
      thickening of the mucosa, but tracheobronchial cartilage was preserved intact.
      Moreover, the comparison between tracheal tissues from tracheostomy and colon
      tissues resected 17 years earlier showed similarities in pathologic findings.
      These findings suggested that inflammatory bowel disease can cause the
      tracheobronchial stenosis.

PMID- 23169026
TI  - Bronchiolitis as a feature of kartagener syndrome: a case report.
AB  - Kartagener syndrome (KS), also known as immotile cilia syndrome or as a primary
      ciliary dyskinesia, is characterized by the triad of situs inversus,
      bronchiectasis, and chronic pansinusitis. A few studies reported that diffuse
      bronchiolitis might be one of the characteristic features of the lung in KS. We
      aimed to present the radiologic characteristics of KS, including diffuse
      bronchiolitis, sinus aplasia, and situs inversus totalis in a single case.

PMID- 23169027
TI  - Tracheal diverticulum.
AB  - Tracheal diverticulum is a rarely encountered entity, usually discovered
      incidentally as an outpouching at the right side on radiography or computed
      tomography (CT). We present the case of a male patient with a tracheal
      diverticulum detected during a work-up for hemoptysis. His thoracic CT scan
      showed a sac formation on the right dorsolateral wall of the trachea. Flexible
      bronchoscopy showed a collapsed entrance to the diverticulum, which could be
      opened by flexible forceps. The mucosal lining of the diverticulum seemed normal,
      without retained secretions or blood. Although with limited clinical
      consequences, tracheal diverticulum must be kept in mind as a reservoir for
      secretions that may cause infection, and also hemoptysis if infected.

PMID- 23169028
TI  - A Retrospective Review of Different Methods of Endobronchial Ultrasound-guided
      Transbronchial Needle Aspiration: A Preliminary Study.
AB  - Transbronchial needle aspiration (TBNA) is a 30 year old procedure for diagnosing
      and staging of lung cancer. There has been renewed interest in TBNA due to the
      development of a curvilinear array endobronchial ultrasound (EBUS) scope for
      TBNA. Reports indicate an increased diagnostic yield compared to standard TBNA.
      In 9 of 11 patients EBUS-TBNA is performed with the second generation Olympus
      EBUS scope (BF-UC180F) and the ViziShot (NA-201SX-4022) needle in addition to the
      standard WANGTM TBNA needle. Three punctures were made by the ViziShot needle.
      The first puncture, the guidewire is partially retracted and without suction the
      needle is moved back and forth inside the lesion. The second puncture, the
      guidewire is completely removed and suction is applied during needle movement.
      The third puncture is without the guidewire but with suction. In five patients
      with a positive diagnosis of cancer, the first punctures were all positive with a
      better quality and quantity of tumor cells. Three patients, standard TBNA needle
      was used, all were positive. Four patients with standard TBNA preceded the EBUS
      TBNA were all positive. We conclude, EBUS TBNA is highly effective and dependable
      and suggest the use of EBUS needle can be simplified. Standard TBNA needle can be
      used for EBUS-TBNA and standard TBNA in relation to EBUS-TBNA needs to be further
      investigated.

PMID- 23169029
TI  - Use of fibrin sealant glue as a treatment for massive hemoptysis.
AB  - In patients presenting with massive hemoptysis, it is often challenging to
      control bleeding. Uncontrolled bleeding can lead to hemodynamic compromise,
      asphyxiation, and high mortality. We present a case of a patient who presented
      with massive hemoptysis, and the use of fibrin sealant glue through a
      bronchoscopic catheter, which was effective in controlling bleeding.

PMID- 23169030
TI  - Standard Techniques of Imaging of IASLC Borders by Endoscopic Ultrasound.
AB  - Linear endoscopic ultrasound is useful in the diagnosis and staging of non-small
      cell lung cancer. Endoscopic ultrasound has been proposed as the first test to be
      used, before bronchoscopy, for staging of lung cancer. The International
      Association for the Study of Lung Cancer has redefined the anatomic borders of
      lymph node stations. We describe the techniques of linear endoscopic ultrasound
      for mapping of the lymph nodes as defined by the International Association for
      the Study of Lung Cancer classification.

PMID- 23169031
TI  - Granulomatous solitary pulmonary nodule.

PMID- 23169032
TI  - Coughing up Suture Stitches and Necrotic Material After Esophagectomy for Cancer.

PMID- 23169033
TI  - Babesia divergens and Neospora caninum apical membrane antigen 1 structures
      reveal selectivity and plasticity in apicomplexan parasite host cell invasion.
AB  - Host cell invasion by the obligate intracellular apicomplexan parasites,
      including Plasmodium (malaria) and Toxoplasma (toxoplasmosis), requires a step
      wise mechanism unique among known host-pathogen interactions. A key step is the
      formation of the moving junction (MJ) complex, a circumferential constriction
      between the apical tip of the parasite and the host cell membrane that traverses
      in a posterior direction to enclose the parasite in a protective vacuole
      essential for intracellular survival. The leading model of MJ assembly proposes
      that Rhoptry Neck Protein 2 (RON2) is secreted into the host cell and integrated
      into the membrane where it serves as the receptor for apical membrane antigen 1
      (AMA1) on the parasite surface. We have previously demonstrated that the AMA1
      RON2 interaction is an effective target for inhibiting apicomplexan invasion. To
      better understand the AMA1-dependant molecular recognition events that promote
      invasion, including the significant AMA1-RON2 interaction, we present the
      structural characterization of AMA1 from the apicomplexan parasites Babesia
      divergens (BdAMA1) and Neospora caninum (NcAMA1) by X-ray crystallography. These
      studies offer intriguing structural insight into the RON2-binding surface groove
      in the AMA1 apical domain, which shows clear evidence for receptor-ligand co
      evolution, and the hyper variability of the membrane proximal domain, which in
      Plasmodium is responsible for direct binding to erythrocytes. By incorporating
      the structural analysis of BdAMA1 and NcAMA1 with existing AMA1 structures and
      complexes we were able to define conserved pockets in the AMA1 apical groove that
      could be targeted for the design of broadly reactive therapeutics.

PMID- 23169034
TI  - Co-analysis of brain structure and function using fMRI and diffusion-weighted
      imaging.
AB  - The study of complex computational systems is facilitated by network maps, such
      as circuit diagrams. Such mapping is particularly informative when studying the
      brain, as the functional role that a brain area fulfills may be largely defined
      by its connections to other brain areas. In this report, we describe a novel, non
      invasive approach for relating brain structure and function using magnetic
      resonance imaging (MRI). This approach, a combination of structural imaging of
      long-range fiber connections and functional imaging data, is illustrated in two
      distinct cognitive domains, visual attention and face perception. Structural
      imaging is performed with diffusion-weighted imaging (DWI) and fiber
      tractography, which track the diffusion of water molecules along white-matter
      fiber tracts in the brain (Figure 1). By visualizing these fiber tracts, we are
      able to investigate the long-range connective architecture of the brain. The
      results compare favorably with one of the most widely-used techniques in DWI,
      diffusion tensor imaging (DTI). DTI is unable to resolve complex configurations
      of fiber tracts, limiting its utility for constructing detailed, anatomically
      informed models of brain function. In contrast, our analyses reproduce known
      neuroanatomy with precision and accuracy. This advantage is partly due to data
      acquisition procedures: while many DTI protocols measure diffusion in a small
      number of directions (e.g., 6 or 12), we employ a diffusion spectrum imaging
      (DSI)(1, 2) protocol which assesses diffusion in 257 directions and at a range of
      magnetic gradient strengths. Moreover, DSI data allow us to use more
      sophisticated methods for reconstructing acquired data. In two experiments
      (visual attention and face perception), tractography reveals that co-active areas
      of the human brain are anatomically connected, supporting extant hypotheses that
      they form functional networks. DWI allows us to create a "circuit diagram" and
      reproduce it on an individual-subject basis, for the purpose of monitoring task
      relevant brain activity in networks of interest.

PMID- 23169035
TI  - Endoscopic removal of a piece of retained pancreatic stent with a novel new
      technique: turned guide-wire looping method.

PMID- 23169036
TI  - Transesophageal endoscopic ultrasound-guided transcarotid fine needle aspiration
      of a positron emission tomography (PET)-positive mediastinal lymph node.

PMID- 23169037
TI  - Endoscopic fenestration of esophageal duplication cysts.

PMID- 23169038
TI  - Paradoxical cerebral embolism during endoscopic esophageal stenting in a patient
      with esophageal cancer.

PMID- 23169039
TI  - Effect of oral fluticasone on refractory peptic esophageal stricture--a new
      therapeutic method.

PMID- 23169040
TI  - A novel traction system for esophageal endoscopic submucosal dissection.

PMID- 23169041
TI  - Utility of the "bear claw", or over-the-scope clip (OTSC) system, to provide
      endoscopic hemostasis for bleeding posterior duodenal ulcers.

PMID- 23169042
TI  - Endoscopic tissue shielding to prevent delayed perforation associated with
      endoscopic submucosal dissection for duodenal neoplasms.

PMID- 23169043
TI  - Video capsule endoscopy findings in Ehlers-Danlos syndrome with recurrent
      gastrointestinal bleeding.

PMID- 23169044
TI  - Endoscopic and endoscopic ultrasound (EUS) features of annular pancreas: duodenal
      ulceration and a dilated bile duct.

PMID- 23169045
TI  - An unusual complication of eosinophilic esophagitis in an adolescent: intramural
      esophageal dissection.

PMID- 23169046
TI  - Three-dimensional ultrasound and maternal bonding, a third trimester study and a
      review.
AB  - OBJECTIVE: To compare the effect of third trimester three-dimensional and four
      dimensional (3D/4D) versus two-dimensional (2D) ultrasound (US) of the fetal face
      on maternal bonding. Studies quantifying the psychological effect of 3D/4D US on
      mothers, pregnant of a fetus with no detectable abnormalities, were reviewed.
      METHODS: One hundred sixty Caucasian women attended a third trimester 3D/4D or 2D
      US examination. Women filled out the Maternal Antenatal Attachment Scale (MAAS) 1
      to 2 weeks before (MAAS1) and 1 to 2 weeks after (MAAS2) the US examination.
      Visibility, recognition and attractiveness were assessed. RESULTS: Within both US
      groups, the MAAS2 scores were significantly higher than the MAAS1 scores (p <
      0.0001). No differences in MAAS scores between the US groups emerged. Visibility
      and recognition were significantly positively related with the increase in MAAS
      scores (p = 0.003 and p = 0.042) in the 3D/4D group. Of 13 psychological studies,
      eight studies evaluated bonding and found no difference between 3D/4D and 2D US.
      The effect of 3D/4D US on satisfaction or perception showed conflicting results,
      and on anxiety/stress, reduction was the same as after 2D US. CONCLUSIONS:
      Bonding increases after either a 3D/4D or 2D US. The effect of 3D/4D US on
      bonding is stronger at better degrees of visibility and recognition.

PMID- 23169047
TI  - Restricted active space spin-flip (RAS-SF) with arbitrary number of spin-flips.
AB  - The restricted active space spin-flip (RAS-SF) approach is a multistate, spin
      complete, variational and size consistent method applicable to systems featuring
      electronic (near-)degeneracies. In contrast to CASSCF it does not involve orbital
      optimizations and so avoids issues such as root-flipping and state averaging.
      This also makes RAS-SF calculations roughly 100-1000 times faster. In this paper
      RAS-SF method is extended to include variable orbital active spaces and three or
      more spin-flips, which allows the study of polynuclear metal systems, triple bond
      dissociations and organic polyradicals featuring more than four unpaired
      electrons. Benchmark calculations on such systems are carried out and comparison
      to other wave-function based, multi-reference methods, such as CASSCF and DMRG
      yield very good agreement, provided that the same active space is employed. Where
      experimental values are available, RAS-SF is found to substantially underestimate
      the exchange coupling constants, if the minimal active space is chosen. However,
      the correct ground state is always obtained. Not surprisingly, inclusion of
      bridge orbitals into the active space can cause the magnitude of the coupling
      constants to increase substantially. Importantly, the ratio of exchange couplings
      in related systems is in much better agreement with experiment than the magnitude
      of the coupling. Nevertheless, the results indicate the need for the inclusion of
      dynamic correlation to obtain better accuracy in minimal active spaces.

PMID- 23169048
TI  - Hepatitis E seroprevalence in recipients of renal transplants or haemodialysis in
      southwest England: a case-control study.
AB  - Locally acquired HEV infection is increasingly recognized in developed countries.
      Anti-HEV IgG seroprevalence has been shown to be high in haemodialysis patients
      in a number of previous studies, employing assays of uncertain sensitivity. The
      aim of this study was to investigate anti-HEV IgG seroprevalence in recipients of
      haemodialysis and renal transplants compared to a control group using a
      validated, highly sensitive assay. Eighty-eight patients with functioning renal
      transplants and 76 receiving chronic haemodialysis were tested for HEV RNA and
      anti-HEV IgG and IgM. Six hundred seventy controls were tested for anti-HEV IgG.
      Anti-HEV IgG was positive in 28/76 (36.8%) of haemodialysis and 16/88 (18.2%) of
      transplant patients. HEV RNA was not found in any patient. 126/670 (18.8%) of
      control subjects were anti-HEV IgG positive. After adjusting for age and sex,
      there was a significantly higher anti-HEV IgG seroprevalence amongst
      haemodialysis patients compared to controls (OR = 1.97, 95% CI = 1.16-3.31, P =
      0.01) or transplant recipients (OR = 2.63, 95% CI = 1.18-6.07, P = 0.02).
      Patients with a functioning transplant showed no difference in anti-HEV IgG
      seroprevalence compared to controls. The duration of haemodialysis or receipt of
      blood products were not significant risk factors for HEV IgG positivity. Patients
      receiving haemodialysis have a higher seroprevalence of anti-HEV IgG than both
      age- and sex-matched controls and a cohort of renal transplant patients. None of
      the haemodialysis patients had evidence of chronic infection. The reason
      haemodialysis patients have a high seroprevalence remains uncertain and merits
      further study.

PMID- 23169050
TI  - Driving diffusionless transformations in colloidal crystals using DNA
      handshaking.
AB  - Many crystals, such as those of metals, can transform from one symmetry into
      another having lower free energy via a diffusionless transformation. Here we
      create binary colloidal crystals consisting of polymer microspheres, pulled
      together by DNA bridges, that induce specific, reversible attractions between two
      species of microspheres. Depending on the relative strength of the different
      interactions, the suspensions spontaneously form either compositionally ordered
      crystals with CsCl and CuAu-I symmetries, or disordered, solid solution crystals
      when slowly cooled. Our observations indicate that the CuAu-I crystals form from
      CsCl parent crystals by a diffusionless transformation, analogous to the
      Martensitic transformation of iron. Detailed simulations confirm that CuAu-I is
      not kinetically accessible by direct nucleation from the fluid, but does have a
      lower free energy than CsCl. The ease with which such structural transformations
      occur suggests new ways of creating unique metamaterials having structures that
      may be otherwise kinetically inaccessible.

PMID- 23169051
TI  - Hopping transport and the Hall effect near the insulator-metal transition in
      electrochemically gated poly(3-hexylthiophene) transistors.
AB  - Despite 35 years of investigation, much remains to be understood regarding charge
      transport in semiconducting polymers, including the ultimate limits on their
      conductivity. Recently developed ion gel gating techniques provide a unique
      opportunity to study such issues at very high charge carrier density. Here we
      have probed the benchmark polymer semiconductor poly(3-hexylthiophene) at
      electrochemically induced three-dimensional hole densities approaching 10(21) cm(
      3) (up to 0.2 holes per monomer). Analysis of the hopping conduction reveals a
      remarkable phenomenon where wavefunction delocalization and Coulomb gap collapse
      are disrupted by doping-induced disorder, suppressing the insulator-metal
      transition, even at these extreme charge densities. Nevertheless, at the highest
      dopings, we observe, for the first time in a polymer transistor, a clear Hall
      effect with the expected field, temperature and gate voltage dependencies. The
      data indicate that at such mobilities (~0.8 cm(2)V(-1) s(-1)), despite the
      extensive disorder, these polymers lie close to a regime of truly diffusive band
      like transport.

PMID- 23169049
TI  - Phosphorylation of VE-cadherin is modulated by haemodynamic forces and
      contributes to the regulation of vascular permeability in vivo.
AB  - Endothelial adherens junctions maintain vascular integrity. Arteries and veins
      differ in their permeability but whether organization and strength of their
      adherens junctions vary has not been demonstrated in vivo. Here we report that
      vascular endothelial cadherin, an endothelial specific adhesion protein located
      at adherens junctions, is phosphorylated in Y658 and Y685 in vivo in veins but
      not in arteries under resting conditions. This difference is due to shear stress
      induced junctional Src activation in veins. Phosphorylated vascular endothelial
      cadherin is internalized and ubiquitinated in response to permeability-increasing
      agents such as bradykinin and histamine. Inhibition of Src blocks vascular
      endothelial cadherin phosphorylation and bradykinin-induced permeability. Point
      mutation of Y658F and Y685F prevents vascular endothelial cadherin
      internalization, ubiquitination and an increase in permeability by bradykinin in
      vitro. Thus, phosphorylation of vascular endothelial cadherin contributes to a
      dynamic state of adherens junctions, but is not sufficient to increase vascular
      permeability in the absence of inflammatory agents.

PMID- 23169052
TI  - Experimental observation of quantum chaos in a beam of light.
AB  - The manner in which unpredictable chaotic dynamics manifests itself in quantum
      mechanics is a key question in the field of quantum chaos. Indeed, very distinct
      quantum features can appear due to underlying classical nonlinear dynamics. Here
      we observe signatures of quantum nonlinear dynamics through the direct
      measurement of the time-evolved Wigner function of the quantum-kicked harmonic
      oscillator, implemented in the spatial degrees of freedom of light. Our setup is
      decoherence-free and we can continuously tune the semiclassical and chaos
      parameters, so as to explore the transition from regular to essentially chaotic
      dynamics. Owing to its robustness and versatility, our scheme can be used to
      experimentally investigate a variety of nonlinear quantum phenomena. As an
      example, we couple this system to a quantum bit and experimentally investigate
      the decoherence produced by regular or chaotic dynamics.

PMID- 23169053
TI  - Scalable organocatalytic asymmetric Strecker reactions catalysed by a chiral
      cyanide generator.
AB  - The Strecker synthesis is one of the most facile methods to access racemic alpha
      amino acids. However, feasible catalytic asymmetric Strecker reactions for the
      large-scale production of enantioenriched alpha-amino acids are rare. Here we
      report a scalable catalytic asymmetric Strecker reaction that uses an accessible
      chiral variant of oligoethylene glycol as the catalyst and KCN to generate a
      chiral cyanide anion. Various alpha-amido sulphone substrates (alkyl, aryl and
      heteroaryl) can be transformed into the optically enriched Strecker products,
      alpha-aminonitriles, with excellent yields and enantioselectivities. Moreover,
      the robust nature of the catalyst enables a 'one-pot' synthesis of
      enantiomerically pure alpha-amino acids starting from alpha-amido sulphones and
      simple catalyst recycling. These features can make this protocol easily adaptable
      to the practical synthesis of unnatural alpha-amino acids.

PMID- 23169054
TI  - Broadband electromagnetic cloaking with smart metamaterials.
AB  - The ability to render objects invisible with a cloak that fits all objects and
      sizes is a long-standing goal for optical devices. Invisibility devices
      demonstrated so far typically comprise a rigid structure wrapped around an object
      to which it is fitted. Here we demonstrate smart metamaterial cloaking, wherein
      the metamaterial device not only transforms electromagnetic fields to make an
      object invisible, but also acquires its properties automatically from its own
      elastic deformation. The demonstrated device is a ground-plane microwave cloak
      composed of an elastic metamaterial with a broad operational band (10-12 GHz) and
      nearly lossless electromagnetic properties. The metamaterial is uniform, or
      perfectly periodic, in its undeformed state and acquires the necessary gradient
      index profile, mimicking a quasi-conformal transformation, naturally from a
      boundary load. This easy-to-fabricate hybrid elasto-electromagnetic metamaterial
      opens the door to implementations of a variety of transformation optics devices
      based on quasi-conformal maps.

PMID- 23169056
TI  - Synthesis of chiral TiO2 nanofibre with electron transition-based optical
      activity.
AB  - The optical chirality induced at the absorption bands due to electronic exciton
      coupling of the transition dipole moments between chromophores in close proximity
      is ubiquitous in helical organic materials. However, inorganic materials with
      optical activity resulting from electronic transitions have not been explored.
      Here we report the synthesis of chiral TiO(2) fibres via transcription of the
      helical structure of amino acid-derived amphiphile fibres through coordination
      bonding interactions between the organics and the TiO(2) source. Upon
      calcination, the as-prepared amorphous TiO(2) double-helical fibres with a pitch
      length of ~100 nm were converted to double-helical crystalline fibres with stacks
      of anatase nanocrystals in an epitaxial helical relationship. Both the amorphous
      and anatase crystalline helical TiO(2) fibres exhibited optical response to
      circularly polarized light at the absorption edge around ~350 nm. This was
      attributed to the semiconductor TiO(2)-based electronic transitions from the
      valence band to the conduction band under an asymmetric electric field.

PMID- 23169055
TI  - Cellulose degradation and assimilation by the unicellular phototrophic eukaryote
      Chlamydomonas reinhardtii.
AB  - Plants convert sunlight to biomass, which is primarily composed of
      lignocellulose, the most abundant natural biopolymer and a potential feedstock
      for fuel and chemical production. Cellulose assimilation has so far only been
      described for heterotrophic organisms that rely on photosynthetically active
      primary producers of organic compounds. Among phototrophs, the unicellular green
      microalga Chlamydomonas reinhardtii is widely known as one of the best
      established model organisms. It occupies many habitats, including aquatic and
      soil ecosystems. This ubiquity underscores the versatile metabolic properties of
      this microorganism. Here we present yet another paradigm of adaptation for C.
      reinhardtii, highlighting its photoheterotrophic ability to utilize cellulose for
      growth in the absence of other carbon sources. When grown under CO(2)-limiting
      conditions in the light, secretion of endo-beta-1,4-glucanases by the cell causes
      digestion of exogenous cellulose, followed by cellobiose uptake and assimilation.
      Phototrophic microbes like C. reinhardtii may thus serve as biocatalysts for
      cellulosic biofuel production.

PMID- 23169057
TI  - Flexible and low-voltage integrated circuits constructed from high-performance
      nanocrystal transistors.
AB  - Colloidal semiconductor nanocrystals are emerging as a new class of solution
      processable materials for low-cost, flexible, thin-film electronics. Although
      these colloidal inks have been shown to form single, thin-film field-effect
      transistors with impressive characteristics, the use of multiple high-performance
      nanocrystal field-effect transistors in large-area integrated circuits has not
      been shown. This is needed to understand and demonstrate the applicability of
      these discrete nanocrystal field-effect transistors for advanced electronic
      technologies. Here we report solution-deposited nanocrystal integrated circuits,
      showing nanocrystal integrated circuit inverters, amplifiers and ring
      oscillators, constructed from high-performance, low-voltage, low-hysteresis CdSe
      nanocrystal field-effect transistors with electron mobilities of up to 22 cm(2)
      V(-1) s(-1), current modulation >10(6) and subthreshold swing of 0.28 V dec(-1).
      We fabricated the nanocrystal field-effect transistors and nanocrystal integrated
      circuits from colloidal inks on flexible plastic substrates and scaled the
      devices to operate at low voltages. We demonstrate that colloidal nanocrystal
      field-effect transistors can be used as building blocks to construct complex
      integrated circuits, promising a viable material for low-cost, flexible, large
      area electronics.

PMID- 23169058
TI  - On-chip transformation optics for multimode waveguide bends.
AB  - Current optical communication systems rely almost exclusively on multimode fibres
      for short- and medium-haul transmissions, and are now expanding into the long
      haul arena. Ultra-high bandwidth applications are the main drive for this
      expansion, based on the ability to spatially multiplex data channels in multimode
      systems. Integrated photonics, on the other hand, although largely responsible
      for today's telecommunications, continues to operate almost strictly in the
      single-mode regime. This is because multimode waveguides cannot be compactly
      routed on-chip without significant inter-mode coupling, which impairs their data
      rate and prevents the use of modal multiplexing. Here we propose a platform for
      on-chip multimode devices with minimal inter-mode coupling, opening up the
      possibilities for integrated multimode optics. Our work combines a novel
      theoretical approach--large-scale inverse design of transformation optics to
      maximize performance within fabrication constraints-with unique grayscale
      lithography fabrication of an exemplary device: a low-crosstalk multimode
      waveguide bend.

PMID- 23169060
TI  - Facile assembly of two 6-membered fused N-heterocyclic rings: a rapid access to
      novel small molecules via Cu-mediated reaction.
AB  - A rapid, versatile and one-pot Cu-mediated domino reaction has been developed for
      facile assembly of two six membered fused N-heterocyclic rings leading to novel
      small molecules as potential inhibitors of PDE4.

PMID- 23169059
TI  - Supporting conditional mouse mutagenesis with a comprehensive cre
      characterization resource.
AB  - Full realization of the value of the loxP-flanked alleles generated by the
      International Knockout Mouse Consortium will require a large set of well
      characterized cre-driver lines. However, many cre driver lines display excision
      activity beyond the intended tissue or cell type, and these data are frequently
      unavailable to the potential user. Here we describe a high-throughput pipeline to
      extend characterization of cre driver lines to document excision activity in a
      wide range of tissues at multiple time points and disseminate these data to the
      scientific community. Our results show that the majority of cre strains exhibit
      some degree of unreported recombinase activity. In addition, we observe frequent
      mosaicism, inconsistent activity and parent-of-origin effects. Together, these
      results highlight the importance of deep characterization of cre strains, and
      provide the scientific community with a critical resource for cre strain
      information.

PMID- 23169061
TI  - Melanocytes--a novel tool to study mitochondrial dysfunction in Duchenne muscular
      dystrophy.
AB  - Dystrophin is a subsarcolemmal protein that, by linking the actin cytoskeleton to
      the extracellular matrix via dystroglycans, is critical for the integrity of
      muscle fibers. Here, we report that epidermal melanocytes, obtained from
      conventional skin biopsy, express dystrophin with a restricted localization to
      the plasma membrane facing the dermal-epidermal junction. In addition the full
      length muscle isoform mDp427 was clearly detectable in melanocyte cultures as
      assessed by immunohistochemistry, RNA, and Western blot analysis. Melanocytes of
      Duchenne muscular dystrophy (DMD) patients did not express dystrophin, and the
      ultrastructural analysis revealed typical mitochondrial alterations similar to
      those occurring in myoblasts from the same patients. Mitochondria of melanocytes
      from DMD patients readily accumulated tetramethylrhodamine methyl ester,
      indicating that they are energized irrespective of the presence of dystrophin
      but, at variance from mitochondria of control donors, depolarized upon the
      addition of oligomycin, suggesting that they are affected by a latent dysfunction
      unmasked by inhibition of the ATP synthase. Pure melanocyte cultures can be
      readily obtained by conventional skin biopsies and may be a feasible and reliable
      tool alternative to muscle biopsy for functional studies in dystrophinopathies.
      The mitochondrial dysfunction occurring in DMD melanocytes could represent a
      promising cellular biomarker for monitoring dystrophinopathies also in response
      to pharmacological treatments.

PMID- 23169062
TI  - Downregulation of JWA promotes tumor invasion and predicts poor prognosis in
      human hepatocellular carcinoma.
AB  - We previously identified JWA as a novel microtubule-associated protein (MAP),
      which is implicated in carcinogenesis and tumor progression. The aims of the
      present study were to investigate the biological action and the prognostic
      significance of JWA in hepatocellular carcinoma (HCC). Quantitative real-time PCR
      and Western blot were used to detect JWA mRNA and protein expression,
      respectively, in stepwise metastatic HCC cell lines and HCC tissues. Short
      hairpin RNA was used to inhibit JWA expression in HCC cells. The effects of JWA
      depletion on cell migration, invasion, adhesion and in vivo metastasis were
      investigated. Immunohistochemistry of JWA was conducted in microarrays with
      tissue from 314 HCC patients who had undergone surgical resection. Prognostic
      significance was assessed using the Kaplan-Meier method and log-rank tests. The
      result showed JWA expression was decreased in the highly metastatic HCC cell
      lines and HCC tissues. Depletion of JWA caused a notable increase in cell
      migration, invasion and adhesion in vitro and metastasis in vivo. Furthermore,
      there was an inverse correlation between JWA expression and FAK expression and
      phosphorylation, RhoA activation and matrix metalloproteinase-2 (MMP-2) activity
      in HCC cells. More notably, multivariate analysis revealed that a low level of
      JWA expression was an independent prognosticator for both recurrence-free and
      overall survival for HCC patients after surgical resection, especially for AFP
      normal HCC patients. Taken together, our data demonstrate that JWA plays a
      crucial role in HCC progression and suggest JWA may be a potential prognostic
      biomarker and therapeutic target for HCC.

PMID- 23169063
TI  - DX5+ CD4+ T cells modulate CD4+ T-cell response via inhibition of IL-12
      production by DCs.
AB  - DX5(+) CD4(+)  T cells have been shown to dampen collagen-induced arthritis and
      delayed-type hypersensitivity reactions in mice. These cells are also potent
      modulators of T-helper cell responses through direct effects on CD4(+)  T cells
      in an IL-4 dependent manner. To further characterize this T-cell population, we
      studied their effect on DCs and the potential consequences on T-cell activation.
      Here, we show that mouse DX5(+) CD4(+)  T cells modulate DCs by robustly
      inhibiting IL-12 production. This modulation is IL-10 dependent and does not
      require cell contact. Furthermore, DX5(+) CD4(+)  T cells modulate the surface
      phenotype of LPS-matured DCs. DCs modulated by DX5(+) CD4(+)  T-cell supernatant
      express high levels of the co-inhibitor molecules PDL-1 and PDL-2. OVA-specific
      CD4(+)  T cells primed with DCs exposed to DX5(+) CD4(+)  T-cell supernatant
      produce less IFN-gamma than CD4(+)  T cells primed by DCs exposed to either
      medium or DX5(-) CD4(+)  T-cell supernatant. The addition of IL-12 to the co
      culture with DX5(+)  DCs restores IFN-gamma production. When IL-10 present in the
      DX5(+) CD4(+)  T-cell supernatant is blocked, DCs re-establish their ability to
      produce IL-12 and to efficiently prime CD4(+)  T cells. These data show that
      DX5(+) CD4(+)  T cells can indirectly affect the outcome of the T-cell response
      by inducing DCs that have poor Th1 stimulatory function.

PMID- 23169064
TI  - Reply: To PMID 22499101.

PMID- 23169065
TI  - New surgical strategy to induce liver hypertrophy: role of MDCT-volumetry to
      monitor and predict liver growth.
AB  - BACKGROUND/AIMS: To describe the role of MDCT-volumetry to monitor and predict
      liver hypertrophy in a recently introduced surgical technique in patients needing
      hepatectomy. METHODOLOGY: This prospective study was approved by the local
      research and ethics committee and patient informed consent was obtained. Twelve
      consecutive patients were selected for associating liver partition and portal
      vein ligation for staged-hepatectomy procedure. The mean absolute the future
      liver-remnant (FLR) and FLR/total liver volume (TLV) ratio was calculated before
      and after surgery to determine the degree of hypertrophy. Six days after surgery
      a new CT-examination was performed to determine the FLR-volume and FLR/TLV. If
      the enlargement of the FLR was the expected a second-step surgery was performed.
      Continuous variables are expressed as mean (range). A p<0.05 was considered
      significant. RESULTS: The mean pre-operative FLR-volume was 402 mL and the
      FLR/TLV was 27%. The mean post-operative FLR-volume 6 days after the first step
      was 702 mL (range 521-1030 mL) being the mean difference between preoperative and
      postoperative FLR volume 303 mL (p<0.0001). The mean volume increase was 80%
      ranged from 21-139%. At day six, FLR/TLV was 46.5% (range 33.5-67.7), morbidity
      was 41% and mortality 0%. CONCLUSIONS: MDCT-volumetry has a key role in decision
      making, monitoring and predicting liver hypertrophy pre- and postoperatively.

PMID- 23169066
TI  - Hematocrit and oxygenation dependence of blood (1)H(2)O T(1) at 7 Tesla.
AB  - Knowledge of blood (1)H2O T1 is critical for perfusion-based quantification
      experiments such as arterial spin labeling and cerebral blood volume-weighted MRI
      using vascular space occupancy. The dependence of blood (1)H2O T1 on hematocrit
      fraction (Hct) and oxygen saturation fraction (Y) was determined at 7 T using in
      vitro bovine blood in a circulating system under physiological conditions. Blood
      (1)H2O R1 values for different conditions could be readily fitted using a two
      compartment (erythrocyte and plasma) model, which are described by a
      monoexponential longitudinal relaxation rate constant dependence. It was found
      that T1 = 2171 +/- 39 ms for Y = 1 (arterial blood) and 2010 +/- 41 ms for Y =
      0.6 (venous blood), for a typical Hct of 0.42. The blood (1)H2O T1 values in the
      normal physiological range (Hct from 0.35 to 0.45, and Y from 0.6 to 1.0) were
      determined to range from 1900 to 2300 ms. The influence of oxygen partial
      pressure (pO2) and the effect of plasma osmolality for different anticoagulants
      were also investigated. It is discussed why blood (1)H2O T1 values measured in
      vivo for human blood may be about 10-20% larger than found in vitro for bovine
      blood at the same field strength.

PMID- 23169067
TI  - A new surgical technique (modified Osaka technique) of sacral resection by
      posterior-only approach: description and preliminary results.
AB  - STUDY DESIGN: Operative technique. OBJECTIVE: To report a new technique for
      sacral resection, with short-term preliminary results. SUMMARY OF BACKGROUND
      DATA: Although various reports analyzed en bloc excision of sacral tumors, there
      are still technical problems to improve protection of nerve roots, preserve
      surrounding structures, and reduce intraoperative bleeding, while maintaining the
      oncological result. METHODS: Thirteen patients were resected for their
      sacrococcygeal tumor by following the described technique. Two patients had
      undergone previous surgery elsewhere. The sacrum was exposed by a posterior
      midline incision and complete soft-tissue dissection. Lateral osteotomies were
      performed through the sacral foramina using a threadwire saw (devised by Tomita
      and Kawahara) and Kerrison rongeurs, to avoid damage to the sacral roots. After
      proximal osteotomy, the sacrum was laterally elevated and mobilized to allow
      dissection of presacral structures. Mean surgical time was 5.5 hours (range; 1.5
      8). Mean blood loss was 2961 mL (range; 1000-8000 mL). RESULTS: Level of
      resection was proximal in 9 patients and at S3 or below in 4. Margins were wide
      in 10 patients, marginal in 1, and intralesional in 2. At a mean follow-up of
      35.5 months, 9 patients were disease free, while the tumor recurred locally in 4
      cases. Complications requiring surgery were seen in 1 case. CONCLUSION: The
      reported technique allows wide margins with preservation of roots, and reduction
      in blood loss and operative time. Indications for posterior-only approach can be
      extended to resection proximal to S3, when there is minimal pelvic invasion and
      none or partial involvement of sacroiliac joints. However, the long-term benefits
      of this technique need to be evaluated.

PMID- 23169068
TI  - Single- versus multilevel fusion for single-level degenerative spondylolisthesis
      and multilevel lumbar stenosis: four-year results of the spine patient outcomes
      research trial.
AB  - STUDY DESIGN: A subanalysis study. OBJECTIVE: To compare surgical outcomes and
      complications of multilevel decompression and single-level fusion with multilevel
      decompression and multilevel fusion for patients with multilevel lumbar stenosis
      and single-level degenerative spondylolisthesis (DS). SUMMARY OF BACKGROUND DATA:
      In patients with DS who are treated surgically, decompression and fusion provide
      a better clinical outcome than decompression alone. Surgical treatment for
      multilevel lumbar stenosis and DS typically includes decompression and fusion of
      the spondylolisthesis segment and decompression with or without fusion for the
      other stenotic segments. To date, no study has compared the results of these 2
      surgical options for single-level DS with multilevel stenosis. METHODS: The
      results from a multicenter randomized and observational study, the Spine Patient
      Outcomes Research Trial comparing multilevel decompression and single-level
      fusion and multilevel decompression and multilevel fusion for spinal stenosis
      with spondylolisthesis, were analyzed. The primary outcome measures were the
      bodily pain and physical function scales of the Medical Outcomes Study 36-item
      Short-Form General Health Survey (SF-36) and the modified Oswestry Disability
      Index at 1, 2, 3, and 4 years postoperatively. Secondary analysis consisted of
      stenosis bothersomeness index, low back pain bothersomeness, leg pain, patient
      satisfaction, and self-rated progress. RESULTS: Overall, 207 patients were
      enrolled for the study, 130 had multlilevel decompression with 1 level fusion and
      77 patients had multilevel decompression and multilevel fusion. For all primary
      and secondary outcome measures, there were no statistically significant
      differences in surgical outcomes between the 2 surgical techniques. However,
      operative time and intraoperative blood loss were significantly higher in the
      multilevel fusion group. CONCLUSION: Decompression and single-level fusion and
      decompression and multilevel fusion provide similar outcomes in patients with
      multilevel lumbar stenosis and single-level DS.

PMID- 23169069
TI  - Comparison of untreated adolescent idiopathic scoliosis with normal controls: a
      review and statistical analysis of the literature.
AB  - STUDY DESIGN: Review and statistical analysis of studies evaluating health
      related quality of life (HRQOL) in adolescents with untreated adolescent
      idiopathic scoliosis (AIS) using Scoliosis Research Society (SRS) outcomes.
      OBJECTIVE: To apply normative values and minimum clinical important differences
      for the SRS-22r to the literature. Identify whether the HRQOL of adolescents with
      untreated AIS differs from unaffected peers and whether any differences are
      clinically relevant. SUMMARY OF BACKGROUND DATA: The effect of untreated AIS on
      adolescent HRQOL is uncertain. The lack of published normative values and minimum
      clinical important difference for the SRS-22r has so far hindered our
      interpretation of previous studies. The publication of this background data
      allows these studies to be re-examined. METHODS: Using suitable inclusion
      criteria, a literature search identified studies examining HRQOL in untreated
      adolescents with AIS. Each cohort was analyzed individually. Statistically
      significant differences were identified by using 95% confidence intervals for the
      difference in SRS-22r domain mean scores between the cohorts with AIS and the
      published data for unaffected adolescents. If the lower bound of the confidence
      interval was greater than the minimum clinical important difference, the
      difference was considered clinically significant. RESULTS: Of the 21 included
      patient cohorts, 81% reported statistically worse pain than those unaffected. Yet
      in only 5% of cohorts was this difference clinically important. Of the 11 cohorts
      included examining patient self-image, 91% reported statistically worse scores
      than those unaffected. In 73% of cohorts this difference was clinically
      significant. Affected cohorts tended to score well in function/activity and
      mental health domains and differences from those unaffected rarely reached
      clinically significant values. CONCLUSION: Pain and self-image tend to be
      statistically lower among cohorts with AIS than those unaffected. The literature
      to date suggests that it is only self-image which consistently differs
      clinically. This should be considered when assessing the possible benefits of
      surgery.

PMID- 23169070
TI  - In vivo inhibition of bone morphogenetic protein-2 on breast cancer cell growth.
AB  - STUDY DESIGN: In vitro and in vivo study. OBJECTIVE: To evaluate the role of
      recombinant human bone morphogenetic protein-2 (rhBMP2) on breast cancer cell
      (MDA-MB-231 cells) growth. SUMMARY OF BACKGROUND DATA: Bone morphogenetic
      proteins (BMPs) are expressed in a variety of human carcinoma cell lines and are
      known to promote tumor invasion and metastasis. However, their roles in tumor
      progression have not been fully clarified. In addition, there is no in vivo study
      regarding the inhibitory effect of BMP2 on breast cancer cell proliferation.
      METHOD: Cell proliferation was determined by BrdU incorporation assay and flow
      cytometry. BMP2 signal transduction pathways were estimated on Western blot.
      Fifteen animals were divided into 2 groups; 1 (control = 5) was breast cancer
      cells alone, while the other (experiment = 5) was rhBMP2 + breast cancer cells.
      Cancer cells were injected into 2 sites (subcutaneous and femur) of nude mice
      with or without BMP2. Tumor size was determined by direct measurements for
      subcutaneous tumor formation and by femur radiographs. Histological and
      immunohistochemical analyses were performed. RESULTS: RhBMP2 inhibited the
      proliferation of MDA-MB-231 cells in vitro. Inhibition was associated with
      changes in both the Smad and Wnt signaling pathways and was ultimately mediated
      through effects on various cell cycle proteins. Furthermore, rhBMP2 inhibited the
      growth of MDA-MB-231 cells injected both subcutaneously and intrafemorally.
      CONCLUSION: In this model using human breast adenocarcinoma cell line, rhBMP2 has
      no stimulatory effect of tumor growth. Therefore, we can provide the basic
      science data to support the utilization in the management of patients with spine
      tumor in the future.

PMID- 23169072
TI  - Spinal manipulative therapy for acute low back pain: an update of the cochrane
      review.
AB  - STUDY DESIGN: Systematic review of interventions. OBJECTIVE: To assess the
      effects of spinal manipulative therapy (SMT) for acute low back pain. SUMMARY OF
      BACKGROUND DATA: SMT is one of many therapies for the treatment of low back pain,
      which is a worldwide, extensively practiced intervention. METHODS: An experienced
      librarian searched for randomized controlled trials (RCTs) in multiple databases
      up to March 13, 2011. RCTs that examined manipulation or mobilization in adults
      with acute low back pain (<6-week duration) were included. The primary outcomes
      were pain, functional status and perceived recovery. Secondary outcomes were
      return-to-work and quality of life. Two authors independently conducted the study
      selection, risk of bias assessment and data extraction. GRADE (grading of
      recommendations assessment, development, and evaluation) was used to assess the
      quality of the evidence. The effects were examined for SMT versus (1) inert
      interventions, (2) sham SMT, (3) other interventions, and (4) SMT as adjunct
      therapy. RESULTS: We identified 20 RCTs (total participants = 2674), 12 (60%) of
      which were not included in the previous review. In total, 6 trials (30% of all
      included studies) had a low risk of bias. In general, for the outcomes of pain
      and functional status, there is low- to very low-quality evidence suggesting no
      difference in effect for SMT when compared with inert interventions, sham SMT or
      as adjunct therapy. There was varying quality of evidence (from very low to
      moderate) suggesting no difference in effect for SMT when compared with other
      interventions. Data were particularly sparse for recovery, return-to-work,
      quality of life, and costs of care. No serious complications were observed with
      SMT. CONCLUSION: SMT is no more effective for acute low back pain than inert
      interventions, sham SMT or as adjunct therapy. SMT also seems to be no better
      than other recommended therapies. Our evaluation is limited by the few numbers of
      studies; therefore, future research is likely to have an important impact on
      these estimates. Future RCTs should examine specific subgroups and include an
      economic evaluation.

PMID- 23169071
TI  - Sacral fracture after instrumented lumbosacral fusion: analysis of risk factors
      from spinopelvic parameters.
AB  - STUDY DESIGN: Retrospective comparative study. OBJECTIVE: To examine the
      incidence and characteristics of key spinopelvic parameters that are correlated
      with sacral fracture development after lumbosacral fusion. SUMMARY OF BACKGROUND
      DATA: Sacral fracture is a possible complication of instrumented lumbosacral
      fusion and this has recently been documented in the literature. Preoperative
      awareness of risk factors concerning spinopelvic parameters and sacral fracture
      may aid in surgical planning to prevent its occurrence. METHODS: All patients who
      underwent instrumented lumbosacral fusion from L2 or above, between 2010 and 2011
      at Gakkentoshi Hospital, were included. RESULTS: A total of 116 patients (47 men
      and 69 women) were evaluated in this study. Average age at surgery was 71 years,
      and the average follow-up period was 19 months. The average number of fixed
      segments was 5, and the average time interval between index surgery and sacral
      fracture development was 42 days. Notably, sacral fractures were identified in 5
      patients (4.3%), all of whom were women. We, therefore, compared the 2 groups of
      female patients (fracture group, n = 5 vs. nonfracture group, n = 64). The
      fracture group had a substantially higher mean pelvic incidence (PI) than the
      nonfracture group (72 degrees  +/- 8 degrees  vs. 51 degrees  +/- 12 degrees ,
      respectively, P < 0.01). The fracture group also had a larger postoperative
      lumbar lordosis (LL)-PI mismatch than the nonfracture group (-26 degrees  +/- 7
      degrees  vs. -7 degrees  +/- 18 degrees , respectively, P < 0.01). CONCLUSION:
      The current review of our patients informs appropriate preoperative planning in
      cases involving lumbosacral fusion for postmenopausal women with a high PI.
      Surgeons should plan to achieve large increases in LL to restore not only
      spinopelvic harmony but also to avoid postoperative sacral fracture. For such
      patients, because it is difficult to consistently achieve a sufficiently large
      LL, we recommend prophylactic iliosacral fixation to protect the sacrum. LEVEL OF
      EVIDENCE: 4.

PMID- 23169073
TI  - Long-term outcomes of anterior spinal fusion for treating thoracic adolescent
      idiopathic scoliosis curves: average 15-year follow-up analysis.
AB  - STUDY DESIGN: Retrospective review. OBJECTIVE: To assess the long-term outcomes
      of anterior spinal fusion (ASF) for treating thoracic adolescent idiopathic
      scoliosis (AIS). SUMMARY OF BACKGROUND DATA: Although ASF is reported to provide
      good coronal and sagittal correction of the main thoracic (MT) AIS curves, the
      long-term outcomes of ASF is unknown. METHODS: A consecutive series of 25
      patients with Lenke 1 MT AIS were included. Outcome measures comprised
      radiographical measurements, pulmonary function, and Scoliosis Research Society
      outcome instrument (SRS-30) scores (preoperative SRS-30 scores were not
      documented). Postoperative surgical revisions and complications were recorded.
      RESULTS: Twenty-five patients were followed-up for 12 to 18 years (average, 15.2
      yr). The average MT Cobb angle correction rate and the correction loss at the
      final follow-up were 56.7% and 9.2 degrees , respectively. The average
      preoperative instrumented level of kyphosis was 8.3 degrees , which significantly
      improved to 18.6 degrees  (P = 0.0003) at the final follow-up. The average
      percent-predicted forced vital capacity and forced expiratory volume in 1 second
      were significantly decreased during long-term follow-up measurements (73% and
      69%; P = 0.0004 and 0.0016, respectively). However, no patient had complaints
      related to pulmonary function. The average total SRS-30 score was 4.0. Implant
      breakage was not observed. All patients, except 1 who required revision surgery,
      demonstrated solid fusion. Late instrumentation-related bronchial problems were
      observed in 1 patient who required implant removal and bronchial tube repair, 13
      years after the initial surgery. CONCLUSION: Overall radiographical findings and
      patient outcome measures of ASF for Lenke 1 MT AIS were satisfactory at an
      average follow-up of 15 years. ASF provides significant sagittal correction of
      the main thoracic curve with long-term maintenance of sagittal profiles. Percent
      predicted values of forced vital capacity and forced expiratory volume in 1
      second were decreased in this cohort; however, no patient had complaints related
      to pulmonary function.

PMID- 23169075
TI  - Considerations for the use of C7 crossing laminar screws in subaxial and
      cervicothoracic instrumentation.
AB  - STUDY DESIGN: Radiographical and biomechanical analyses. OBJECTIVE: To determine
      the applicability of C7 laminar screw fixation using radiographical and
      biomechanical analysis. SUMMARY OF BACKGROUND DATA: The unique anatomy of C7
      creates a challenge during instrumentation at the caudal aspect of the cervical
      spine and cervicothoracic junction. The C7 lateral mass is often smaller,
      resulting in increased difficulty for pedicle screw placement. The use of
      crossing laminar screw fixation is common in the upper cervical and thoracic
      spine; its use at the C7 level, however, has only recently appeared in the
      literature. METHODS: Radiographical: Computed tomographic scans from 72 patients
      were used to measure laminar thickness, spinolaminar angle, and length (i.e.,
      from the spinolaminar junction to the contralateral lamina-lateral mass junction)
      for each C7 vertebrae. Biomechanical: The C2 and C7 vertebrae from 13 cadaveric
      cervical spines were obtained, scanned using pQCT (Stratec Electronics,
      Pforzheim, Germany) for bone mineral density, and then instrumented in the
      following manner: (1) bilateral crossing intralaminar screws in C2, (2) bilateral
      crossing intralaminar screws in C7, and (3) bilateral pedicle screws in each C7
      specimen after completion of laminar screw biomechanical testing. Each specimen
      was cyclically loaded for 5000 cycles after which axial screw pullout tests were
      performed. RESULTS: Radiographical: Mean laminar thickness and length were 5.67
      +/- 1.00 mm and 25.49 +/- 2.73 mm, respectively. Biomechanical: The mean load to
      failure was 610.3 +/- 251 N for C7 laminar screws, 666.33 +/- 373N for C7 pedicle
      screws, and 355 +/- 250 N for C2 laminar screws. A student t test indicated no
      statistical difference in pullout strength between C7 laminar and C7 pedicle
      screws (P = 0.6). CONCLUSION: The radiographical anatomy at C7 suggests that
      intralaminar screws can be placed in the majority of patients. The in vitro
      biomechanical analysis performed indicates that C7 laminar screws are as strong
      as C7 pedicle screws and significantly stronger than laminar screws at C2. LEVEL
      OF EVIDENCE: N/A.

PMID- 23169076
TI  - The natural history of degenerative spondylolisthesis of the cervical spine with
      2- to 7-year follow-up.
AB  - STUDY DESIGN: Retrospective study. OBJECTIVE: To determine whether cervical
      degenerative spondylolisthesis is unstable and/or progresses. SUMMARY OF
      BACKGROUND DATA: Cervical degenerative spondylolisthesis is relatively common in
      the elderly. However, there are no reports regarding its natural history.
      METHODS: We identified 27 patients with cervical degenerative spondylolisthesis
      (3.9%) from a database of 697 patients, using cervical radiographs. All had
      neutral and dynamic lateral radiographs at baseline and at a minimum of 24 months
      later (mean 39 mo, range, 24-92 mo). The mean age of the patients at the initial
      visit was 59.0 years (range, 50-83 yr). Male to female ratio was 16:11.
      Radiographical findings and clinical symptoms related to spondylolisthesis were
      assessed at initial and final follow-up. RESULTS: Eleven patients had cervical
      spondylolisthesis at C4-C5, 9 at C3-C4, 6 at C5-C6, and 1 at C2-C3. Initially, 6
      had anterolisthesis and 21 had retrolisthesis. At baseline, 3 of 6 patients with
      anterolisthesis and 7 of 21 patients with retrolisthesis had translation of more
      than 2 mm on dynamic views. At baseline, 11 had no cervical symptoms, 8 had
      cervicalgia, 7 had radiculopathy, and 1 had myelopathy. At the final visit, none
      of the anterolistheses or retrolistheses had progressed. At the final visit, 7 of
      10 patients with initial translation of more than 2 mm on dynamic views had no
      change. Of 17 patients with less than 2 mm of initial dynamic motion, 3 patients
      progressed to have more than 2 mm of dynamic translation. All 3 of these had
      retrolisthesis initially. None had clinical worsening of symptoms at the final
      visit. CONCLUSION: The natural history of cervical degenerative anterolisthesis
      and retrolisthesis seems to be stable during 2 years to nearly 8 years. Although
      those with retrolisthesis seem to have a higher propensity to increase their
      subluxation, none experienced dislocation or neurological injury. LEVEL OF
      EVIDENCE: 4.

PMID- 23169077
TI  - TBNA: should EBUS be used on all lymph node aspirations?

PMID- 23169078
TI  - Confidence.

PMID- 23169079
TI  - A randomized prospective trial of the utility of rapid on-site evaluation of
      transbronchial needle aspirate specimens.
AB  - BACKGROUND: Previous studies have suggested an increased diagnostic yield for
      flexible bronchoscopic transbronchial needle aspirate (TBNA) specimens from lymph
      nodes when using rapid on-site evaluation by cytopathology but were limited by a
      lack of randomization, suggesting that selection bias may have contributed to its
      higher reported yield with TBNA. OBJECTIVES: The purpose of our study was to
      determine the effect of rapid on-site evaluation (ROSE) on the diagnostic power
      of TBNA. METHODS: The study is a prospective randomized controlled trial.
      Diagnoses made by procedures were recorded prospectively. The primary endpoint
      was diagnostic yield. RESULTS: Thirty-four patients were randomized to the ROSE
      group and 34 patients to the no-ROSE group. Specimen adequacy was 94% in the ROSE
      group and 88% in the no-ROSE group (P=0.67). The TBNA diagnostic yield was
      similar in both groups: ROSE, 55%; no-ROSE, 53% (P=1.000). Neoplastic diagnoses
      were made in 59% and 50% of ROSE and no-ROSE patients, respectively (P=0.63).
      There were no significant differences in the number of needle passes, procedure
      duration, or amount of sedatives used. There was a trend toward a decrease in the
      number of transbronchial biopsies needed in the ROSE group. CONCLUSIONS: Previous
      reports of increased diagnostic yield of ROSE were subject to selection bias.
      Routine use of ROSE in all TBNA procedures was not associated with a reduced
      procedure time or sedative use. ROSE may be beneficial by decreasing the need for
      transbronchial biopsy and the associated risk or if the probability of malignancy
      is likely. We recommend ROSE in selected patients over all TBNA procedures.

PMID- 23169080
TI  - Airway measurements in tracheobronchial stenosis using endobronchial
      ultrasonography during stenting.
AB  - PURPOSE: To assess airway measurements, endobronchial ultrasonography (EBUS) and
      multidetector, row computed tomography (MDCT) images were compared in patients
      with tracheal stenosis. METHODS: Airway stenting was performed on 31 patients, 25
      malignant and 6 benign. EBUS and MDCT images were compared before intervention to
      assess the degree of airway narrowing at 212 sites. Of these, 130 sites were
      considered normal and 82 abnormal. For malignant stenosis, airway measurements
      were taken at 160 sites including 112 normal and 48 abnormal. For benign
      stenosis, airway measurements were taken at 52 sites including 18 normal and 34
      abnormal. This technique enables the EBUS probe to measure the distal end to the
      proximal end of the stenosis whereby the inflated balloon size changes according
      to the degree of stenosis. RESULTS: The diameter and length of the stenotic sites
      measured by EBUS and MDCT were nearly equal in all patients. Significant
      correlation was seen at all 212 sites (r=0.805, P<0.0001), 130 normal (r=0.758,
      P<0.0001) and 82 abnormal (r=0.654, P<0.0001). For malignant cases, there was
      significant correlation in a total of 160 sites (r=0.810, P<0.0001), 112 normal
      (r=0.782, P<0.0001) and 48 abnormal (r=0.564, P<0.0001). Benign cases showed
      significant correlations in total 52 sites (r=0.780, P<0.0001), 18 normal
      (r=0.778, P<0.0001) and 34 abnormal (r=0.731, P<0.0001). CONCLUSION: This EBUS
      technique was successful in establishing accurate airway measurements for
      suitable airway stent sizes in interventional procedures, especially in cases
      with tracheobronchial malacia.

PMID- 23169081
TI  - Electromagnetic navigational bronchoscopy: an effective and safe approach to
      diagnose peripheral lung lesions unreachable by conventional bronchoscopy in high
      risk patients.
AB  - PURPOSE: The purpose of this study was to investigate the diagnostic yield and
      safety of electromagnetic navigation bronchoscopy (ENB) on peripheral lung
      lesions deemed otherwise unreachable using conventional bronchoscopy in high-risk
      patients. METHODS: This was a retrospective chart review involving adults (age,
      18 y and older) who underwent ENB for pulmonary lesions located at the fourth
      order of bronchi or beyond, including subpleural lesions, at the University of
      Chicago Medical Center. Forty-eight patients underwent ENB by 3 different trained
      operators from January 2006 to September 2008. There was a short period of
      inactivity when the device was withdrawn from the market. ENB was reserved for
      use only in lesions at the fourth order of bronchi or beyond, including
      subpleural lesions, in patients who are considered high risk for other invasive
      procedures. Pathologic, cytologic, and microbiologic studies were carried out on
      recovered samples. Postprocedural chest radiographs were obtained on all patients
      to detect the presence of procedure-associated complications. RESULTS: ENB led to
      the diagnosis of 37 of 48 (77%) lesions not amenable to conventional
      bronchoscopic biopsy in high-risk patients. Of the 37 successful procedures,
      malignancy was identified in 18 patients (49%). Nonsmall cell lung cancer (NSCLC)
      was diagnosed 16 times, whereas both small cell lung cancer and carcinoid tumor
      were diagnosed once. In addition, 4 lesions (11%) were found to be infectious, 1
      lesion (3%) was found to be granulomatous (noncaseating), and 1 lesion (3%) was
      diagnosed as organizing pneumonia. Of the 37 successful diagnoses, 13 lesions
      (35%) were determined to be nonpathologic, benign lesions. Eleven procedures
      (22%) were unsuccessful in yielding the correct pathologic diagnosis. Nine of the
      11 unsuccessful ENB cases (82%) were found to be malignant, 9 of which were
      identified as NSCLC. Other than NSCLC, 1 neuroendocrine tumor (9%) and 1
      metastatic transitional cell carcinoma of the kidney (9%) were identified by
      alternative, invasive testing methods. The 2 other lesions unsuccessfully
      diagnosed by ENB were not malignant. One was determined to be infection
      (histoplasmosis) and the other was diagnosed as an organizing pneumonia. The most
      common complication noted by all modalities was pneumothorax. ENB carried a
      pneumothorax rate of 5 of 49 (10%), 2 of which required chest tube insertion for
      treatment. In the ENB success group, 4 cases (11%) were complicated by
      pneumothoraces. In the ENB failure group, 1 case (9%) was complicated by a
      pneumothorax. CONCLUSIONS: ENB is an effective and low-risk modality for
      diagnosing pulmonary lesions that are difficult to reach in patients deemed to be
      at high risk for invasive procedures. Although no clear criteria for the use of
      ENB currently exist, our study shows that diagnostic sampling can be obtained in
      77% of lesions at the fourth order of bronchi or beyond, including subpleural
      lesions. CLINICAL IMPLICATIONS: ENB is an effective, minimally invasive method
      for the diagnosis of pulmonary nodules previously deemed unreachable by
      conventional bronchoscopy in high-risk patients and harbors a low complication
      rate.

PMID- 23169082
TI  - Endobronchial ultrasound knowledge, implementation, and perceived barriers after
      attendance at a dedicated hands-on course.
AB  - Endobronchial ultrasound (EBUS) is a relatively new technology in the field of
      pulmonary medicine. To determine EBUS knowledge, current clinical utilization,
      and perceived barriers to EBUS implementation, we surveyed physicians who had
      previously attended a 2-day hands-on EBUS course in our center. Our survey
      response rate was 51%. Overall, we found that more than one-third of course
      participants were currently performing linear EBUS and that over half had access
      to EBUS for their patients through another physician in their center. EBUS
      knowledge was excellent and many physicians used EBUS in their current clinical
      setting in the diagnosis of sarcoidosis, mediastinal lymphadenopathy, and lung
      cancer. Reported barriers to EBUS implementation included the high cost of
      equipment (73%), high per procedure cost (23%), inadequate support staff (32%),
      and limitations regarding use of sedation and anesthesia (18%). Only 14% cited
      lack of adequate training as a barrier to EBUS implementation, and none believed
      that low patient volumes for EBUS was a barrier to its implementation. It seems
      that participation in an EBUS course is useful in helping physicians incorporate
      EBUS in their practice, but barriers remain, some of which may not be modifiable
      through such activities.

PMID- 23169083
TI  - Randomized comparison of 2 different methods of intrabronchial lidocaine delivery
      during flexible bronchoscopy: a pilot study.
AB  - BACKGROUND: Adequate anesthesia during bronchoscopy is essential for patient
      comfort and tolerance, and for achieving a good sample yield. The Enk device was
      designed for use during anesthesia for awake intubations. The objective of this
      study was to compare patient tolerability and frequency of cough during flexible
      bronchoscopy according to the method of administration of local anesthetic.
      METHODS: Patients were randomized to receive topical lidocaine either nebulized
      through an Enk device or with conventional injection through the working channel
      of the bronchoscope. All patients, physicians, and the assisting nurse completed
      a questionnaire that included items on tolerability, ease of procedure, frequency
      of cough, etc. The response was marked on a 10-cm-long visual analog scale, with
      a higher score indicating better outcome. RESULTS: Fifty patients were divided
      into 2 groups of 25 patients each. The mean +/- standard deviation duration of
      procedure was no different in the Enk group than in the syringe group (12.8 +/-
      7.5 and 10.8 +/- 6.9 min, respectively). There was no statistically significant
      difference between the 2 groups in the scores of each of the questions.
      CONCLUSIONS: The Enk device showed a nonsignificant trend toward greater ease of
      procedure for the operator with no difference in the frequency of cough. For the
      patients, there was no significant difference. A further investigation through
      comparison with other methods, such as transtracheal installation, over a larger
      population may yield more significant results. TRIAL REGISTRATION: This trial was
      registered with the Local Research Ethics Committee and with International
      Standard Randomised Controlled Trial Number.

PMID- 23169084
TI  - Tracheal bronchus in the adult population.
AB  - BACKGROUND: Tracheal bronchus is an abnormal bronchus that comes directly off the
      lateral wall of the trachea (ie, above the main carina) and supplies ventilation
      to the upper lobe. A new nomenclature and classification system has been
      developed for tracheal bronchus. The purpose of this study was to evaluate the
      anatomic and bronchoscopic features of tracheal bronchus subtypes on the basis of
      the new nomenclature and classification system. METHODS: A retrospective study
      was performed using data from eight patients with tracheal bronchus. RESULTS: The
      incidence of tracheal bronchus was found to be 0.06% (8 of 12,648 patients) and
      the distribution of the subtypes was as follows: displaced type (7 patients,
      87.5%) and supernumerary type (1 patient, 12.5%). Among the patients with
      displaced tracheal bronchus, 6 had displaced preeparterial (75%), 1 had displaced
      preeparterial and posteparterial tracheal bronchus (12.5%), and 1 patient had
      supernumerary eparterial tracheal bronchus (12.5%). In all cases, the tracheal
      bronchi were located on the right side of the trachea. The mean distance between
      the origin of the tracheal bronchus and main carina was 16.25 mm (range, 5 to 40
      mm). In 1 case, posteparterial bronchus was detected with its orifice on the
      lateral side of the intermediate bronchus. CONCLUSIONS: Displaced preeparterial
      tracheal bronchus was the most common subtype of tracheal bronchus. Furthermore,
      in all cases, tracheal bronchus was located on the right side of the trachea.
      Both flexible bronchoscopy and computed tomography of the chest were crucial for
      its diagnosis.

PMID- 23169085
TI  - Multiple endobronchial polyps.
AB  - Multiple endobronchial polyps are a rare finding. We describe a case of multiple
      benign endobronchial polyps in a 60-year-old woman who presented with a chronic
      cough and occasional hemoptysis. Chest computed tomography revealed bilateral
      basal cylindrical bronchiectasis, with filling defects in both main bronchi.
      Bronchoscopy revealed the presence of polyps in the distal trachea, both main
      bronchi, and in the lobar and segmental bronchi of all lobes of both lungs, with
      lesions from 2 to 10 mm in diameter. Larger lesions were treated with argon
      plasma coagulation. Histopathology was consistent with benign fibroepithelial
      polyps. Culture from bronchial washings isolated Pseudomonas aeruginosa, and the
      patient was treated with ciprofloxacin followed by a prolonged course of
      azithromycin. Symptoms improved, and repeat bronchoscopy at 3 and 6 months
      revealed complete resolution of all polyps.

PMID- 23169086
TI  - Endobronchial metastasis from transitional cell carcinoma of the urinary bladder.
AB  - Endobronchial metastasis of urinary bladder cancer is rare. A 71-year-old man
      presented with shortness of breath and cough. He was diagnosed with prostate
      adenocarcinoma and transitional cell carcinoma of the urinary bladder in the
      past. Bronchoscopy identified grape-like endotracheal lesions clustering over the
      distal tracheal wall obstructing 50% of the tracheal lumen and causing an almost
      complete obstruction of the left main bronchus. There was also extrinsic
      compression of the left main bronchus along with patchy nodular tumoral lesions
      involving the right main and the intermediate bronchial walls. Histologic
      examination of the lesions showed endobronchial metastasis from the bladder
      cancer. Bronchoscopy is a highly valuable method for evaluating the uncommon
      endobronchial metastases. Therapeutic bronchoscopy in such cases can contribute
      to improving quality of life and may impact the survival of the patient. Our
      patient survived for 5 months after a therapeutic bronchoscopy.

PMID- 23169087
TI  - Primary tracheomalacia and persistent wheezing in cystic fibrosis during infancy.
AB  - Persistent wheezing, poorly responsive to bronchodilator therapy, raises concerns
      about the progression of cystic fibrosis-related lung disease. We describe 3
      infants with such symptoms who were observed to have primary tracheomalacia. The
      diagnoses were made using flexible bronchoscopy during spontaneous respiration.
      Early recognition of this etiology can limit unnecessary investigation and the
      overuse of empirical treatments such as oral and inhaled corticosteroids.

PMID- 23169088
TI  - Flexible bronchoscopic removal of a fractured metallic tracheostomy tube.
AB  - Patients frequently require a tracheostomy for a variety of indications, but its
      prolonged use is associated with several complications, including fracture of the
      tube. Metallic tracheostomy tubes, which are often used in developing countries,
      are predisposed to such a complication essentially because of corrosion from
      prolonged used. We report 2 cases of a fractured tracheostomy tube inserted into
      the central airways, with different clinical presentations. Fractured pieces were
      successfully removed using a flexible bronchoscope under topical anesthesia.

PMID- 23169089
TI  - Primary squamous cell carcinoma of the thyroid: an unusual presentation.
AB  - Primary squamous cell carcinoma of the thyroid (PSCCT) is a rare malignancy with
      a poor prognosis. PSCCT usually presents as an enlarging neck mass and can cause
      stridor, hoarseness, and shortness of breath because of its penchant for local
      invasion. Long-term survival requires early detection and complete surgical
      excision, as the tumor is resistant to chemotherapy and radiation therapy. We
      present a patient with PSCCT without evidence of neck mass on presentation, who
      presented instead with shortness of breath, stridor, and evidence of an upper
      airway obstruction on spirometry. Recognition of a possible airway obstruction
      led to bronchoscopy, identification of the endobronchial obstruction, and
      successful definitive resection of the malignancy.

PMID- 23169090
TI  - Effect of antitubercular treatment on tumorous endobronchial tuberculosis.
AB  - Four cases of tumorous endobronchial tuberculosis (EBTB) were prospectively
      evaluated to assess the effect of antitubercular treatment (ATT) on tumorous
      EBTB. All 4 patients received standard ATT (isoniazid, rifampicin, ethambutol,
      and pyrizinamide for 2 months followed by isoniazid and rifampicin). At the
      completion of ATT, bronchoscopy was repeated in all cases and no residual
      structural abnormality of the bronchus was identified. Short-course ATT without
      corticosteroid is effective in preventing residual endobronchial complication of
      tumorous EBTB.

PMID- 23169091
TI  - Transbronchial occlusion of a malignant bronchopleural fistula with cyanoacrylate
      glue.
AB  - A 73-year-old man who had undergone surgery for lingual cancer, followed by
      radiation therapy and chemotherapy, presented with severe dyspnea. A chest
      radiograph revealed a left tension pneumothorax. An immediate tube thoracostomy
      alleviated his dyspnea. A chest computed tomography scan showed multiple large
      cystic tumors in both lungs. Squamous cell carcinoma was cytologically proven in
      the pleural effusion. A malignant bronchopleural fistula due to a metastatic
      pulmonary tumor was diagnosed. Surgical interventions were tried twice. However,
      air leakage occurred when the rapidly recurring tumor caused bilateral
      pneumothoraces. Thus, bronchoscopic closure was conducted. A flexible video
      bronchoscope and a thin catheter were inserted into the targeted left
      bronchiolus. The lumen of the catheter was filled with water. Cyanoacrylate glue
      and lipiodol were mixed in 2 syringes, and the mixture was slowly injected and
      then flushed with water. As soon as the lipiodol accumulation was visualized by
      radiograph fluoroscopy, the air leakage stopped. Pleurodesis with the
      intrathoracic administration of OK-432 was added to both pleural cavities, and
      the left and right chest tubes were removed on the third and fifth days,
      respectively. The patient was discharged the following day. However, he died of
      the disease a month later.

PMID- 23169092
TI  - Foreign body granulomatosis in a patient with a factitious disorder.
AB  - A 42-year-old woman was hospitalized with fever and hypoxemia. The workup for
      fever was unrevealing. A computed tomographic scan of the chest showed
      centrilobular, small, nodular opacities throughout both the lung fields. A
      flexible bronchoscopy with transbronchial biopsy was performed. Pathology
      specimens consisted of intravascular foreign material with birefringent
      properties suggestive of microcrystalline cellulose. It was later determined that
      the patient was self-injecting herself with crushed pill fragments through a
      tunneled central venous catheter. The central venous catheter was removed and
      fever resolved.

PMID- 23169093
TI  - Broncholithiasis:  "incidental finding during bronchoscopy"-case reports and
      review of the literature.
AB  - Broncholithiasis is a rare condition defined as the presence of a calcified
      fragment of tissue within the lumen of a tracheobronchial tree. We present a case
      of broncholithiasis in an asymptomatic patient with chronic lingular atelectasis.

PMID- 23169094
TI  - Silver nitrate in interventional pulmonology: treating a case of persistent
      bronchopleural fistula.
AB  - Bronchopleural fistula (BPF) is a communication between the pleural space and the
      bronchial tree. A BPF occurs when an injured bronchus fails to heal; the
      condition is associated with high morbidity. The treatment of persistent BPF
      includes various surgical procedures. Conventional surgical strategies such as
      thoracoplasty or chest wall fenestration carry significant mortality and long
      term morbidity with pain and deformity. Reducing the morbidity of therapy with a
      minimal access approach is, therefore, appealing. In recent years, bronchoscopic
      management of BPF in terms of recognizing the site of fistula and blocking the
      leaking segment with many agents available has attained success and has been
      considered an established mode of management. The use of silver nitrate in
      treatment of BPF has staged a comeback, offering very good results.

PMID- 23169095
TI  - Migrating laryngeal foreign body.
AB  - We report the case of a 6-year-old boy who presented with a 2-month history of
      stridor and respiratory difficulty, preceded 1 month earlier by dry cough. The
      evaluation before admission revealed glottic narrowing due to diffuse
      inflammatory changes. On examination, the patient was seen to have biphasic
      stridor and respiratory distress with diminished breath sounds throughout both
      lung fields. Laryngoscopy revealed multiple polyps and granulation tissue causing
      marked laryngeal narrowing. No foreign body was detected in the larynx. Elective
      tracheostomy was performed before proceeding to bronchoscopy. The latter
      procedure revealed a foreign body in the left main bronchus. One week after the
      foreign body extraction, repeat bronchoscopy revealed nearly total disappearance
      of polyps and granulation tissues. The tracheostomy tube was removed and the
      patient recovered uneventfully. To our knowledge, this is the first reported case
      of stridor caused by a migrating laryngeal foreign body. A thorough endobronchial
      examination should be carried out in patients with unexplained laryngeal polyps
      and granulation tissue.

PMID- 23169096
TI  - A 56-year-old man with a normal chest radiograph, elevated CA 19-9, and multiple
      hepatic lesions.
AB  - Carbohydrate antigen (CA 19-9) is a tumor marker associated with colorectal
      malignancies. Elevated CA 19-9 is seen in patients with benign and malignant
      disease of the lung. We present an unusual case of small cell lung cancer
      associated with elevated CA 19-9.

PMID- 23169097
TI  - Clinical application of virtual bronchoscopic navigation system for peripheral
      lung lesions.
AB  - Transbronchial lung biopsy is an indispensable method for the diagnosis of
      peripheral lung lesions; however, the diagnostic yield still remains
      unsatisfactory. Endobronchial ultrasound with guide sheath (EBUS-GS) is an
      excellent method for the decision of biopsy points and has contributed to
      improvements in diagnostic yield, but the decision of choosing the proper
      bronchus depends on the individual ability of each bronchoscopist. To clarify the
      usefulness of the virtual bronchoscopic navigation system (VBN), we evaluated the
      diagnostic yield and time required to determine the target lesion. Fifty-seven
      cases using EBUS-GS with VBN (VBN/EBUS-GS group) and 55 cases using EBUS-GS (EBUS
      GS group) were compared. In the VBN/EBUS-GS group, computer software detects the
      air density in the bronchi from the computed tomography image and imports a
      detailed virtual Bronchoscopic Image. After inserting the starting position and
      the peripheral target lesion, the software depicts the most ideal route to the
      target lesion during the bronchoscopic procedure. EBUS is then used to confirm
      the accuracy of the route. Diagnostic yield was 84.2% for the VBN/EBUS-GS group
      and 80.0% for EBUS-GS group. The required time to determine the biopsy position
      was significantly less in the VBN/EBUS-GS group (5.54 +/- 0.57 min in VBN/EBUS-GS
      group vs. 9.27 +/- 0.86 min in EBUS-GS group, P<0.01). In conclusion, VBN proved
      useful in shortening the time needed to determine the biopsy position.

PMID- 23169098
TI  - Lung carcinoma with a secondary Trousseau's syndrome.

PMID- 23169099
TI  - EBUS in a 6-year-old boy with enlarged hilar lymph nodes.

PMID- 23169100
TI  - Evidence from NMR interaction studies challenges the hypothesis of direct lipid
      transfer from L-FABP to malaria sporozoite protein UIS3.
AB  - UIS3 is a malaria parasite protein essential for liver stage development of
      Plasmodium species, presumably localized to the membrane of the parasitophorous
      vacuole formed in infected cells. It has been recently proposed that the soluble
      domain of UIS3 interacts with the host liver fatty acid binding protein (L-FABP),
      providing the parasite with a pathway for importing exogenous lipids required for
      its rapid growth. This finding may suggest novel strategies for arresting
      parasite development. In this study, we have investigated the interaction between
      human L-FABP and the soluble domain of Plasmodium falciparum UIS3 by NMR
      spectroscopy. The amino acid residue-specific analysis of (1)H,(15) N-2D NMR
      spectra excluded the occurrence of a direct interaction between L-FABP (in its
      unbound and oleate-loaded forms) and Pf-UIS3. Furthermore, the spectrum of Pf
      UIS3 was unchanged when oleate or phospholipids were added. The present
      investigation entails a reformulation of the current model of host-pathogen lipid
      transfer, possibly redirecting research for early intervention against malaria.

PMID- 23169102
TI  - What is the evidence for antibodies to LAMP-2 in the pathogenesis of ANCA
      associated small vessel vasculitis?
AB  - PURPOSE OF REVIEW: This review critically analyses the data implicating
      antibodies to lysosome associated membrane protein-2 (hLAMP-2) in ANCA-associated
      vasculitis (AAV). It addresses recent controversies over prevalence of anti-hLAMP
      2 antibodies as well as their potential for diagnosis and monitoring disease
      activity. RECENT FINDINGS: Anti-hLAMP-2 antibodies were first described in the
      1990s and have become the focus of intense clinical interest in the past 4 years.
      This followed the demonstration of their very high prevalence in untreated
      patients presenting with AAV but absence when patients were in remission. The
      data also demonstrated molecular mimicry between hLAMP-2 and the bacterial
      protein FimH. The same group later confirmed the original findings and showed the
      anti-hLAMP-2 autoantibodies have different kinetics to those recognising
      myeloperoxidase and proteinase-3 and are less likely to be detectable when the
      disease is in remission. By contrast, a different group reported a lower
      prevalence of anti-hLAMP-2 antibodies in AAV and questioned their relevance to
      pathogenesis. Critical analysis of these studies suggests that the differences
      are largely attributable to selection criteria of the AAV patients studied and
      the assays used. SUMMARY: Anti-hLAMP-2 antibodies are frequently found in AAV but
      attempts to define their consequences have been frustrated by lack of generally
      available assays for them.

PMID- 23169101
TI  - Prognostic biomarkers in osteoarthritis.
AB  - PURPOSE OF REVIEW: Identification of patients at risk for incident disease or
      disease progression in osteoarthritis remains challenging, as radiography is an
      insensitive reflection of molecular changes that presage cartilage and bone
      abnormalities. Thus there is a widely appreciated need for biochemical and
      imaging biomarkers. We describe recent developments with such biomarkers to
      identify osteoarthritis patients who are at risk for disease progression. RECENT
      FINDINGS: The biochemical markers currently under evaluation include anabolic,
      catabolic, and inflammatory molecules representing diverse biological pathways. A
      few promising cartilage and bone degradation and synthesis biomarkers are in
      various stages of development, awaiting further validation in larger populations.
      A number of studies have shown elevated expression levels of inflammatory
      biomarkers, both locally (synovial fluid) and systemically (serum and plasma).
      These chemical biomarkers are under evaluation in combination with imaging
      biomarkers to predict early onset and the burden of disease. SUMMARY: Prognostic
      biomarkers may be used in clinical knee osteoarthritis to identify subgroups in
      whom the disease progresses at different rates. This could facilitate our
      understanding of the pathogenesis and allow us to differentiate phenotypes within
      a heterogeneous knee osteoarthritis population. Ultimately, such findings may
      help facilitate the development of disease-modifying osteoarthritis drugs
      (DMOADs).

PMID- 23169103
TI  - Letter from the editor.

PMID- 23169104
TI  - Annular rupture leading to fatal complications in an elderly patient with
      calcified aortic and mitral annulus undergoing transapical aortic valve
      implantation.
AB  - This case illustrates the awareness that must be taken of the high morphological
      risk due to the calcifications of both, the aortic and mitral annulus in elderly
      patients when performing transapical aortic valve implantation. In an 86-year
      old, multimorbid woman (logistic EuroSCORE = 27%) with symptomatic aortic
      stenosis (annular diameter = 23.4 mm) and severe mitral annular calcification,
      the implantation of a 26-mm Edwards SAPIEN (Edwards Lifesciences, Irvine,
      California, United States) valve in aortic position was primary successful, with
      no paravalvular leakage, valve instability, or coronary malperfusion. Second, a
      persisting transmural bleeding led to hypovolemic shock, which could not be
      stabilized even after going on cardiopulmonary bypass, and the patient died in
      the operation room. The autopsy showed a subvalvular ventricular rupture due to a
      transmural perforation of the calcified fibrotic annulus during valvuloplasty. 

PMID- 23169105
TI  - Simple and controlled method to avoid hyperperfusion of the right arm following
      axillary artery cannulation for extracorporeal membrane oxygenator support.
AB  - The right axillary artery has become the cannulation site of choice for
      establishment of extracorporeal membrane oxygenator support in many centers.
      Dissection and cannulation of this vessel are simple and safe in the majority of
      patients. Typically, a side graft is used to avoid malperfusion of the right arm.
      Although this protocol offers many advantages, a common complication is the
      critical hyperperfusion of the right arm. Subsequent compartment syndrome and
      decline of antegrade inflow of oxygenated blood, especially into the brain and
      coronary arteries, can be life threatening in such critical patients. We describe
      herein a simple yet effective and controlled technique to avoid this particular
      problem. 

PMID- 23169106
TI  - Left atrial radiofrequency ablation associated with valve surgery: midterm
      outcomes.
AB  - BACKGROUND: Left atrial ablation is a surgical standard technique for the
      treatment of persistent or chronic atrial fibrillation (p-AF and c-AF,
      respectively).Objective The aim of the study is to evaluate midterm results of
      left atrial ablation according to modified Maze procedure in patients affected by
      p-AF or c-AF and concomitant mitral or aortic valve disease requiring surgical
      treatment. METHODS: A total of 108 patients (age, mean +/- standard deviation
      [SD]: 66 +/- 8.5 years) underwent left atrial ablation by means of unipolar (n =
      62) or bipolar (n = 66) radiofrequency for p-AF (n = 28) or c-AF (n = 100) in
      association with mitral (n = 93) or mitral and aortic valve (n = 35) surgery.
      RESULTS: In-hospital mortality was 0.8%. Patients with preoperative c-AF had
      preoperative greater value of left atrial diameter (56.7 +/- 7.4 vs. 52 +/- 9 mm,
      p = 0.05) than those with p-AF. At 9 years after Maze procedure, 86% (n = 24/28)
      of patients with preoperative p-AF were in sinus rhythm versus 28% (n = 27/95)
      with c-AF (p < 0.0001). Preoperative c-AF and left atrial diameter of 75 mm or
      more predicted atrial fibrillation recurrence. In patients in sinus rhythm
      compared with those in residual atrial fibrillation, survival was 100 versus 86%
      +/- 6.4%, New York Heart Association class was 1.3 +/- 0.5 versus 1.7 +/- 0.6,
      and need of lifelong anticoagulation therapy was 43 versus 91% (p < 0.05, for all
      comparisons). CONCLUSIONS: Left atrial Maze procedure for p-AF offers better
      chances to conversion in sinus rhythm as compared with long-standing c-AF.
      Survival, functional status, and quality of life are superior in patients who
      benefit from sinus rhythm.

PMID- 23169107
TI  - Risk factors predicting the successful function and use of autogenous
      arteriovenous fistulae for hemodialysis.
AB  - BACKGROUND: For patients with end-stage renal failure hemodialysis with an
      autogenous arteriovenous fistula (AVF) has proven to be the ideal vascular
      access. OBJECTIVE: The aim of this study is to discover potential predictors of a
      well-functioning hemodialysis fistula. METHODS: From December 2009 to March 2011,
      80 patients undergoing first time AVF creation were enrolled in our retrospective
      study. We analyzed pre- and postoperative vessel diameters and flow
      characteristics gained by duplex ultrasonography (DUS) and intraoperative
      ultrasound transit-time flow measurements regarding intraoperative blood flow and
      pulsatility index (PI). Follow-up was defined until the end of the first month
      with regular hemodialysis, 10 weeks after AVF creation. We performed statistical
      analyses by employing Spearman correlation, t test, analysis of variance, chi2
      test, and receiver operating characteristics (ROC). RESULTS: At the end of the
      follow-up, 62 patients (78%) featured functioning AVFs and 18 patients (22%)
      featured nonfunctioning AVFs. Factors influencing AVF function were radial artery
      diameter (chi2 = 5.23, p = 0.02), intraoperative flow (chi2 = 7.09, p = 0.01),
      intraoperative PI (chi2 = 6.5, p = 0.01), and postoperative flow (chi2 = 16.29, p
      = 0.01). According to the ROC analyses, we could develop cut-off values for
      predicting an ideal AVF function: radial artery diameter more than 2.3 mm,
      cephalic vein diameter more than 2.7 mm, intraoperative mean flow more than 113
      mL/min, PI less than 1.4, and postoperative mean flow more than 160 mL/min.
      CONCLUSION: Intraoperative ultrasound transit-time flow measurements gained at
      surgery and postoperative follow-up with DUS can help identify AVFs that are
      unlikely to function and therefore need early intervention.

PMID- 23169108
TI  - A new screening method for the directed evolution of thermostable bacteriolytic
      enzymes.
AB  - Directed evolution is defined as a method to harness natural selection in order
      to engineer proteins to acquire particular properties that are not associated
      with the protein in nature. Literature has provided numerous examples regarding
      the implementation of directed evolution to successfully alter molecular
      specificity and catalysis(1). The primary advantage of utilizing directed
      evolution instead of more rational-based approaches for molecular engineering
      relates to the volume and diversity of variants that can be screened(2). One
      possible application of directed evolution involves improving structural
      stability of bacteriolytic enzymes, such as endolysins. Bacteriophage encode and
      express endolysins to hydrolyze a critical covalent bond in the peptidoglycan
      (i.e. cell wall) of bacteria, resulting in host cell lysis and liberation of
      progeny virions. Notably, these enzymes possess the ability to extrinsically
      induce lysis to susceptible bacteria in the absence of phage and furthermore have
      been validated both in vitro and in vivo for their therapeutic potential(3-5).
      The subject of our directed evolution study involves the PlyC endolysin, which is
      composed of PlyCA and PlyCB subunits(6). When purified and added extrinsically,
      the PlyC holoenzyme lyses group A streptococci (GAS) as well as other
      streptococcal groups in a matter of seconds and furthermore has been validated in
      vivo against GAS(7). Significantly, monitoring residual enzyme kinetics after
      elevated temperature incubation provides distinct evidence that PlyC loses lytic
      activity abruptly at 45  degrees C, suggesting a short therapeutic shelf life,
      which may limit additional development of this enzyme. Further studies reveal the
      lack of thermal stability is only observed for the PlyCA subunit, whereas the
      PlyCB subunit is stable up to ~90  degrees C (unpublished observation). In
      addition to PlyC, there are several examples in literature that describe the
      thermolabile nature of endolysins. For example, the Staphylococcus aureus
      endolysin LysK and Streptococcus pneumoniae endolysins Cpl-1 and Pal lose
      activity spontaneously at 42  degrees C, 43.5  degrees C and 50.2  degrees C,
      respectively(8-10). According to the Arrhenius equation, which relates the rate
      of a chemical reaction to the temperature present in the particular system, an
      increase in thermostability will correlate with an increase in shelf life
      expectancy(11). Toward this end, directed evolution has been shown to be a useful
      tool for altering the thermal activity of various molecules in nature, but never
      has this particular technology been exploited successfully for the study of
      bacteriolytic enzymes. Likewise, successful accounts of progressing the
      structural stability of this particular class of antimicrobials altogether are
      nonexistent. In this video, we employ a novel methodology that uses an error
      prone DNA polymerase followed by an optimized screening process using a 96 well
      microtiter plate format to identify mutations to the PlyCA subunit of the PlyC
      streptococcal endolysin that correlate to an increase in enzyme kinetic stability
      (Figure 1). Results after just one round of random mutagenesis suggest the
      methodology is generating PlyC variants that retain more than twice the residual
      activity when compared to wild-type (WT) PlyC after elevated temperature
      treatment.

PMID- 23169109
TI  - Correction of first trimester biochemical aneuploidy screening markers for
      smoking status: influence of gestational age, maternal ethnicity and cigarette
      dosage.
AB  - OBJECTIVE: To examine the gestational age, maternal ethnicity and cigarette
      dosage effects of the reduction of maternal serum pregnancy-associated plasma
      protein A (PAPP-A) and free-beta human chorionic gonadotrophin (free hCGbeta) in
      smokers. METHODS: Maternal serum PAPP-A and free hCGbeta corrected for
      confounders, excluding smoking, in first trimester smokers and nonsmokers were
      compared by gestational age, maternal ethnicity and cigarette dosage. A small set
      of second trimester smokers and nonsmoker controls were analysed for PAPP-A along
      with free hCGbeta and assessed for gestational age effects of smoking. RESULTS:
      Pregnancy-associated plasma protein A reduction by smoking in the first trimester
      was not influenced by gestational age, however free hCGbeta levels were only
      significantly reduced in weeks 12 and 13 in smokers. Ethnicity and cigarette
      dosage were also found to influence the reduction of both makers in smokers in
      the first trimester. In second trimester smokers, PAPP-A was found to be reduced
      by less and free hCGbeta reduced by more than in the first trimester, although no
      second trimester gestational age effect on smoking was found. CONCLUSIONS:
      Current methods of correcting for smoking status may be an oversimplification of
      a more complex subject.

PMID- 23169110
TI  - Highly efficient SO2 capture through tuning the interaction between anion
      functionalized ionic liquids and SO2.
AB  - A strategy to improve SO(2) capture through tuning the electronegativity of the
      interaction site in ILs has been presented. Two types of imidazolium ionic
      liquids that include less electronegative sulfur or carbon sites were used for
      the capture of SO(2), which exhibit extremely highly available capacity, rapid
      absorption rate and excellent reversibility.

PMID- 23169111
TI  - A study of bicycle and passenger car collisions based on insurance claims data.
AB  - In Sweden, bicycle crashes are under-reported in the official statistics that are
      based on police reports. Statistics from hospital reports show that cyclists
      constitute the highest percentage of severely injured road users compared to
      other road user groups. However, hospital reports lack detailed information about
      the crash. To get a more comprehensive view, additional data are needed to
      accurately reflect the casualty situation for cyclists.An analysis based on 438
      cases of bicycle and passenger car collisions is presented, using data collected
      from insurance claims. The most frequent crash situations are described with
      factors as to where and when collisions occur, age and gender of the involved
      cyclists and drivers. Information on environmental circumstances such as road
      status, weather- and light conditions, speedlimits and traffic environment is
      also included. Based on the various crash events, a total of 32 different
      scenarios have been categorized, and it was found that more than 75% were
      different kinds of intersection related situations. From the data, it was
      concluded that factors such as estimated impact speed and age significantly
      influence injury severity.The insurance claims data complement the official
      statistics and provide a more comprehensive view of bicycle and passenger car
      collisions by considering all levels of crash and injury severity. The detailed
      descriptions of the crash situations also provide an opportunity to find
      countermeasures to prevent or mitigate collisions. The results provide a useful
      basis, and facilitates the work of reducing the number of bicycle and passenger
      car collisions with serious consequences.

PMID- 23169112
TI  - Pedestrian Injuries By Source: Serious and Disabling Injuries in US and European
      Cases.
AB  - US and European pedestrian crash cases were analyzed to determine frequency of
      injury by body region and by the vehicle component identified as the injury
      source. US pedestrian data was drawn from the Pedestrian Crash Data Study (PCDS).
      European pedestrian data was drawn from the German In-Depth Accident Study
      (GIDAS). Results were analyzed in terms of both serious injury (AIS 3+) and
      disabling injury estimated with the Functional Capacity Index (FCI). The results
      are presented in parallel for a more complete international perspective on
      injuries and injury sources. Lower extremity injury from bumper impact and
      head&face injury from windshield impact were the most frequent combinations for
      both serious and disabling injuries. Serious lower extremity injuries from bumper
      contact occurred in 43% of seriously injured pedestrian cases in US PCDS data and
      35% of European GIDAS cases. Lower-extremity bumper injuries also account for
      more than 20% of disability in both datasets. Serious head &face injuries from
      windshield contact occur in 27% of PCDS and 15% of GIDAS serious injury cases.
      While bumper impacts primarily result in lower extremity injury and windshield
      impacts are most often associated with head & face injuries, the hood and hood
      leading edge are responsible for serious and disabling injuries to a number of
      different body regions. Therefore, while it is appropriate to focus on lower
      extremity injury when studying bumper performance and on head injury risk when
      studying windshield impact, pedestrian performance of other components may
      require better understanding of injury risk for multiple body regions.

PMID- 23169113
TI  - Fatal Vehicle-to-Bicyclist Crashes in Sweden - an In-Depth Study of injuries and
      vehicle sources.
AB  - Designing effective vehicle-based countermeasures for vulnerable road users
      demands an understanding of the relationship between injury and injury source.
      The aim of this study was to explore this association for bicyclists in fatal
      real-life-crashes. All fatal crashes in Sweden where a bicyclist was killed when
      hit by the front of a passenger car between 2002 and 2008 were studied in detail
      using on-scene data. An analysis was performed to determine the body region
      containing the injury causing death, and the point of the car accountable for the
      fatal injury. These crashes were then compared to a previous study with the same
      selection criteria for vehicle-to-pedestrian fatal crashes.A combined analysis
      revealed that the dominating injury mechanism was head/neck injury from the
      windshield area. The most frequent injurious windshield parts were structural;
      the frame and lower parts of the glass area with instrument panel situated within
      the head's line of motion. This study indicates that bicyclists' injury sources
      were located more rearwardly on the car (e.g. windshield relative to hood), in
      comparison to injury sources in fatal vehicle-to-pedestrian crashes.If
      countermeasures to prevent fatal bicyclist injury in vehicle impacts were to be
      concentrated on mitigating head and thorax impact to the structural parts of the
      windshield, a dominant share of fatal bicyclist crashes could be prevented. This
      study shows that pedestrian countermeasures also have a potential for reducing
      injury in bicyclist crashes, but indicating that these countermeasures should be
      extended to address higher areas of the windshield.

PMID- 23169114
TI  - An Analysis of Distance from Collision Site to Pedestrian Residence in Pedestrian
      versus Automobile Collisions Presenting to a Level 1 Trauma Center.
AB  - This study tests the hypothesis that most pedestrian collisions occur near
      victims' homes. Patients involved in automobile versus pedestrian collisions who
      presented to the emergency department at a Level I trauma center between January
      2000 and December 2009 were included in the study. Patient demographics were
      obtained from the trauma registry. Home address was determined from hospital
      records, collision site was determined from the paramedic run sheet, and the
      shortest walking distance between the collision site and pedestrian residence was
      determined using Google Maps. We summarized distances for groups with the median
      and compared groups using the Kruskal-Wallis rank test. We identified 1917
      pedestrian injury cases and identified both residence address and collision
      location for 1213 cases (63%). Forty-eight percent of the collisions were near
      home (within 1.1 km, 95% CI 45-51%). Median distance from residence to collision
      site was 1.4 km (interquartile range 0.3-7.4 km). For ages 0-17, the median
      distance 0.7 km, and 59% (95% CI 54-63%) of collisions occurred near home. For
      ages 65 and older, the median distance was 0.6 km and 65% (95% CI 55-73%) were
      injured near home. Distance did not differ by sex, race, ethnicity, or blood
      alcohol level. More severe injuries (Injury Severity Score >= 16) occurred
      further from home than less severe injuries (median 1.9 km vs. 1.3 km, p=.01).
      Patients with a hospital stay of 3 days or less were injured closer to home
      (median 1.3 km) than patients with a hospital stay of 4 days or more (median 1.8
      km, p=.001). Twenty-two percent were injured within the same census tract as
      their home, 22% on the boundary of their home census tract, and 55% in a
      different census tract.

PMID- 23169115
TI  - Young unlicensed drivers and passenger safety restraint use in u.s. Fatal
      crashes: concern for risk spillover effect?
AB  - Young unlicensed drivers are more likely to be in fatal crashes and to engage in
      high-risk driving behaviors like impaired driving, speeding, and driving
      unrestrained. In a crash context, the influence of these high-risk behaviors may
      spillover to adversely affect passenger safety restraint use. We conducted an
      analysis of the Fatality Analysis Reporting System from years 1996-2008. Fatal
      crashes involving a driver aged 15-24 years and at least one passenger aged 15-24
      years were included. Logistic regression with generalized estimating equations
      was undertaken to assess the effect of unlicensed driving on passenger restraint
      use. We controlled for established predictors of passenger restraint use
      including driver restraint use, gender, number of occupants, driver drinking,
      number of occupants, crash year, and crash location (rural vs. urban). 102,092
      passengers were involved in fatal crashes during the time period with 64,803
      unique drivers. 6,732 (10.51%) were never licensed drivers and 5,603 (8.8%) were
      drivers with suspended, revoked, or expired licenses. Rates of unlicensed driving
      ranged from 17.7% to 22.1% and increased over time. While passengers in fatal
      crashes averaged a mere 40.9% restraint use, passengers of never and invalidly
      licensed drivers had a further decreased odds of wearing a safety restraint (OR
      0.73, 95% CI 0.69-0.77, p<0.001) and (OR 0.84, 95% CI 0.79-0.90, p<0.001).
      Unlicensed driving is involved in a disproportionate and increasing number of
      preventable crash fatalities and plays a detrimental role in the lifesaving
      safety behaviors of their passengers. Our findings highlight an alarming peer
      influence between unlicensed drivers and passengers, placing increased emphasis
      on the need to better understand and characterize this present and growing
      threat.

PMID- 23169116
TI  - Characteristics of interstate motorcoach carriers with elevated rates of crashes
      and inspection violations.
AB  - Widely-publicized fatal motorcoach crashes have caused public concern about their
      safety. This study estimated crash and violation rates among interstate
      motorcoach carriers based on 2005-2011 data obtained from the Federal Motor
      Carrier Safety Administration (FMCSA). Motorcoach carriers with relatively high
      crash and violation rates were compared with those with better safety records.
      The principal component analysis produced three orthogonal factors that captured
      the majority (63 percent) of the total variance in the data set. Motorcoach
      carriers operating 10 or fewer motorcoaches were more likely to be classified in
      both the high crash rate and the high inspection and violation rates group. Those
      carriers with 10 or fewer years in business were more likely to be classified in
      the high inspection and violation rates group. The vast majority of motorcoach
      carriers with problematic safety records were non-scheduled route providers
      (charters). Scheduled-service motorcoach carriers identified as providing at
      least occasional curbside service, defined as picking up or dropping off
      passengers at a place other than a traditional terminal at the origin or
      destination, had an increased risk of involvement in fatal crashes compared with
      other scheduled-service carriers (1.4 per 100 vehicles, 95% C.I.: 0.1-2.7 versus
      0.2, 95% C.I.: 0.0-0.5). The data did not indicate whether crashes or violations
      occurred during the trips where curbside service was provided. These findings
      suggest that FMCSA and the states need to have the resources necessary for close
      monitoring of motorcoach carriers, particularly high-risk ones such as small and
      less experienced motorcoach carriers.

PMID- 23169117
TI  - Safety challenges and oversight in the motorcoach industry: attitudes and
      perceptions of drivers, roadside inspectors, and federal investigators.
AB  - Interstate motorcoach travel has been the fastest-growing transportation mode in
      recent years. To identify challenges to monitoring compliance with motorcoach
      safety regulations and to examine factors affecting safety, four focus groups
      with a total of 32 participants were conducted during 2011, one with federal
      safety investigators, one with state motor carrier inspectors, and two with
      motorcoach drivers. Investigators and inspectors expressed concern about
      falsified logbooks, inadequate sleep among motorcoach drivers, hazards from
      speeding motorcoaches, practices by motorcoach carriers to mask ownership and
      avoid oversight, and difficulties keeping up with rapid motorcoach industry
      growth. Drivers described problems with getting sufficient sleep, pressure to
      drive longer than permitted, and fears of motor carriers giving them less work if
      they turned down driving jobs. Drivers said that driving 72-74 mph was acceptable
      in light traffic. To help assess workload among personnel performing safety
      oversight, data on numbers of motor carriers, commercial motor vehicles, federal
      investigators, and state inspectors were obtained from the Federal Motor Carrier
      Safety Administration (FMCSA). The data suggested a heavy workload (2.13
      inspectors per 1,000 commercial motor vehicles). The focus groups of inspectors,
      investigators, and drivers indicated the existence of serious motorcoach safety
      problems, provided insight about the multiple factors contributing to them, and
      described major obstacles to effective safety oversight. The qualitative nature
      of focus group research means that these notable findings will need to be
      measured using other methods such as surveys and observational studies.

PMID- 23169118
TI  - Analysis of firetruck crashes and associated firefighter injuries in the United
      States.
AB  - Motor vehicle crashes are the second leading cause of death for on-duty
      firefighters. Firetruck crashes, occurring at a rate of approximately 30,000
      crashes per year, have potentially dire consequences for the vehicle occupants
      and for the community if the firetruck was traveling to provide emergency
      services. Data from the United States Fire Administration and the National
      Highway Traffic Safety Administration shows that firefighters neglect to buckle
      their seatbelts while traveling in a fire apparatus, thus putting themselves at a
      high risk for injuries if the truck crashes, especially in rollover crashes.
      Despite national regulations and departmental guidelines aiming to improve safety
      on fire apparatuses, belt use among firefighters remains dangerously low. The
      results from this study indicate that further steps need to be taken to improve
      belt use. One promising solution would be to redesign firetruck seatbelts to
      improve the ease of buckling and to accommodate wider variations in firefighter
      sizes.

PMID- 23169119
TI  - Contextualizing exposures and experiences of behaviors that influence the risk of
      crash injury in latino adolescent males.
AB  - The largest proportion of mortality burden for U.S. Latino adolescent males is
      attributed to motor vehicle crashes. In a traffic safety context, relatively
      little is known about how these youth regularly interface within their own
      culture and how developmental factors as well as behavior choices influence their
      risk of crash injury. This complex sociobehavioral interface has implications for
      how this group perceives, interprets, and navigates the adolescent period that is
      coupled with passenger and driver experiences. We conducted a mixed method study
      with triangulation design inclusive of in-depth ethnically concordant interviews.
      Purposive sampling was used to select Latino adolescent males (15-18 years old).
      Validated measures of acculturation, sensation and reward seeking, and threat
      avoidance were administered. Using a standard discussion guide with prompts, we
      explored respondents' perceptions of Latino cultural themes, ideas, attitudes,
      and experiences regarding passenger and driver safety. Codes were created and
      defined as concepts emerging from the data in an inductive fashion. Using the
      constant comparative method, we compared coded text to identify novel themes and
      expand existing themes until thematic saturation was reached. Despite Latino
      adolescent males expressing a high value of passenger and driver safety, this did
      not uniformly manifest in their reports of real-life behaviors. Their experiences
      reflected a dense frequency of exposure to risky behavior modeling and crash
      injury risk. Opportunities for Latino youth and family-focused risk reduction
      skill strategies are plentiful. Further research should explore how culture
      influences parent perceptions of safety and risk and the extent to which family
      structure shapes the modeling of risk that their adolescent faces.

PMID- 23169120
TI  - Underreporting of driver alcohol involvement in United States police and hospital
      records: capture-recapture estimates.
AB  - This paper analyzes what portion of US nonfatal crashes are alcohol-involved and
      how well police and hospitals detect involvement. A capture recapture model
      estimated alcohol involvement from levels detected by police and hospitals and
      the extent of detection overlap. We analyzed 550,933 Crash Outcome Data
      Evaluation System driver records from 2006-2008 police crash report censuses
      probabilistically linked to hospital inpatient and emergency department (ED)
      discharge censuses for CT, KY (admissions only), MD, NE, NY, SC, and UT. We
      computed national estimates from NHTSA's General Estimates System.Nationally an
      estimated 7.5% of drivers in nonfatal crashes and 12.9% of nonfatal crashes were
      alcohol-involved. (Crashes often involve multiple drivers but rarely are two
      alcohol-involved.) Police correctly identified an estimated 32% of alcohol
      involved drivers in non-fatal crashes including 48% in injury crashes. Excluding
      KY, police in the six states reported 47% of alcohol involvement for cases
      treated in EDs and released and 39% for admitted cases. In contrast, hospitals
      reported 28% of involvement for ED cases and 51% for admitted cases.
      Underreporting varied widely between states. Police reported alcohol involvement
      for 44% of those who hospitals reported were alcohol-involved, while hospitals
      reported alcohol involvement for 33% of those who police reported were alcohol
      involved. Police alcohol reporting completeness rose with police-reported driver
      injury severity. At least one system reported 62% of alcohol involvement. Police
      and hospitals need to communicate better about alcohol involvement. Despite the
      proven effectiveness of brief alcohol intervention, EDs rarely detect, much less
      intervene with crash-involved drinking drivers. Both police and EDs particularly
      need to assess alcohol involvement in minor injury better.

PMID- 23169121
TI  - Gender and Age Differences among Teen Drivers in Fatal Crashes.
AB  - To identify age and gender differences among teen drivers in fatal crashes, we
      analyzed FARS data for 14,026crashes during 2007-2009. Compared with female
      teenagers, crashes of male teenagers were significantly more likely to involve
      BACs of 0.08% or more (21% vs. 12%), speeding (38% vs. 25%), reckless driving
      (17% vs. 14%), night driving (41% vs. 36%) and felony crashes (hit-and-run,
      homicide, or manslaughter) (8% vs. 6%) (all chi(2) p<0.001). Conversely, crashes
      of female teenagers were more likely to involve right angle ("t-bone") crashes
      (23% vs. 17%). Some crash characteristics associated with males and known to play
      a major role in crash causation also are more common in the youngest teenagers;
      for example, crashes of drivers age 15 or 16 were more likely than crashes of
      older teens to involve speeding or reckless driving. Crashes of drivers with BACs
      of 0.08% or higher increased with age in both genders. Some age effects differed
      by gender: for example, the proportion of crashes of female teens that involved
      speeding dropped from 38% to 22% between ages 15 and 19, while for males about
      38% of crashes at each age involved speeding. The gender and age differences
      observed in teen drivers suggest opportunities for targeted driver training - for
      example, simulator training modules specifically tailored for male or female
      teenagers. Technology-based tools could also be developed to help parents to
      focus on the reckless driving tendencies of their sons. Insurance companies
      should consider ways to incentivize young males to drive more responsibly.

PMID- 23169122
TI  - Predicting rib fracture risk with whole-body finite element models: development
      and preliminary evaluation of a probabilistic analytical framework.
AB  - This study sought to develop a strain-based probabilistic method to predict rib
      fracture risk with whole-body finite element (FE) models, and to describe a
      method to combine the results with collision exposure information to predict
      injury risk and potential intervention effectiveness in the field. An age
      adjusted ultimate strain distribution was used to estimate local rib fracture
      probabilities within an FE model. These local probabilities were combined to
      predict injury risk and severity within the whole ribcage. The ultimate strain
      distribution was developed from a literature dataset of 133 tests. Frontal
      collision simulations were performed with the THUMS (Total HUman Model for
      Safety) model with four levels of delta-V and two restraints: a standard 3-point
      belt and a progressive 3.5-7 kN force-limited, pretensioned (FL+PT) belt. The
      results of three simulations (29 km/h standard, 48 km/h standard, and 48 km/h
      FL+PT) were compared to matched cadaver sled tests. The numbers of fractures
      predicted for the comparison cases were consistent with those observed
      experimentally. Combining these results with field exposure informantion (DeltaV,
      NASS-CDS 1992-2002) suggests a 8.9% probability of incurring AIS3+ rib fractures
      for a 60 year-old restrained by a standard belt in a tow-away frontal collision
      with this restraint, vehicle, and occupant configuration, compared to 4.6% for
      the FL+PT belt. This is the first study to describe a probabilistic framework to
      predict rib fracture risk based on strains observed in human-body FE models.
      Using this analytical framework, future efforts may incorporate additional
      subject or collision factors for multi-variable probabilistic injury prediction.

PMID- 23169123
TI  - Upper and lower neck loads in belted human surrogates in frontal impacts.
AB  - The upper and lower neck loads in the restrained Hybrid III dummy and Test Device
      for Human Occupant Restraint (THOR) were computed in simulated frontal impact
      sled tests at low, medium, and high velocities; repeatability performance of the
      two dummies were evaluated at all energy inputs; peak forces and moments were
      compared with computed loads at the occipital condyles and cervical-thoracic
      junctions from tests using post mortem human surrogates (PMHS). A custom sled
      buck was used to position the surrogates. Repeated tests were conducted at each
      velocity for each dummy and sufficient time was allowed to elapse between the two
      experiments. The upper and lower neck forces and moments were determined from
      load cell measures and its locations with respect to the ends of the neck. Both
      dummies showed good repeatability for axial and shear forces and bending moments
      at all changes in velocity inputs. Morphological characteristics in the neck
      loading responses were similar in all surrogates, although the peak magnitudes of
      the variables differed. In general, the THOR better mimicked the PMHS response
      than the Hybrid III dummy, and factors such as neck design and chest compliance
      were attributed to the observed variations. While both dummies were not designed
      for use at the two extremes of the tested velocities, results from the present
      study indicate that, currently the THOR may be the preferred anthropomorphic
      testing device in crashworthiness research studies and full-scale vehicle tests
      at all velocities.

PMID- 23169124
TI  - An In-depth Study of Abdominal Injuries Sustained by Car Occupants in Frontal
      Crashes.
AB  - Currently, neither abdominal injury risk nor rear seat passenger safety is
      assessed in European frontal crash testing. The objective of this study was to
      provide real world in-depth analysis of the factors related to abdominal injury
      for belted front and rear seat occupants in frontal crashes. Rear occupants were
      significantly more at risk of AIS 2+ and 3+ abdominal injury, followed by front
      seat passengers and then drivers. This was still the case even after controlling
      for occupant age. Increasing age was separately identified as a factor related to
      increased abdominal injury risk in all seating positions. One exception to this
      trend concerned rear seated 15 to 19 year olds who sustained moderate to serious
      abdominal injury at almost the same rate as rear occupants aged 65+.No strong
      association was seen between AIS 2+ abdominal injury rates and gender. The
      majority of occupant body mass indices ranged from underweight to obese. Across
      that range, the AIS 2+ abdominal injury rates were very similar but a small
      number of very obese and extremely obese occupants outside of the range did
      exhibit noticeably higher rates. An analysis of variance in the rate of AIS 2+
      abdominal injury with different restraint systems showed that simple belt
      systems, as used by most rear seat passengers, were the least protective.
      Increasing sophistication of the restraint system was related to lower rates of
      injury. The ANOVA also confirmed occupant age and crash severity as highly
      associated with abdominal injury risk. The most frequently injured abdominal
      organs for front seat occupants were the liver and spleen. Abdominal injury
      patterns for rear seat passengers were very different. While they also sustained
      significant injuries to solid organs, their rates of injury to the hollow organs
      (jejunum-ileum, mesentary, colon) were far higher even though the rate of
      fracture of two or more ribs did not differ significantly between seat positions.
      These results have implications for the design of restraint systems, particularly
      in relation to the occurrence of abdominal injury. They also raise issues of
      crash protection for older occupants as well as the protection afforded in
      different seating positions.

PMID- 23169125
TI  - Sequential biomechanics of the human upper thoracic spine and pectoral girdle.
AB  - Thoracic spine flexibility affects head motion, which is critical to control in
      motor vehicle crashes given the frequency and severity of head injuries. The
      objective of this study is to investigate the dynamic response of the human upper
      thoracic region. An original experimental/analytical approach, Isolated Segment
      Manipulation (ISM), is introduced to quantify the intact upper thoracic spine
      pectoral girdle (UTS-PG) dynamic response of six adult post-mortem human subjects
      (PMHS). A continuous series of small displacement, frontal perturbations were
      applied to the human UTS-PG using fifteen combinations of speed and constraint
      per PMHS. The non-parametric response of the T1-T6 lumped mass segment was
      obtained using a system identification technique. A parametric mass-damper-spring
      model was used to fit the non-parametric system response. Mechanical parameters
      of the upper thoracic spine were determined from the experimental model and
      analyzed in each speed/constraint configuration. The natural frequencies of the
      UTS-PG were 22.9 +/- 7.1 rad/sec (shear, n=58), 32.1 +/- 7.4 rad/sec (axial,
      n=58), and 27.8 +/- 7.7 rad/sec (rotation, n=65). The damping ratios were 0.25 +/
      0.20 (shear), 0.42 +/- 0.24 (axial), and 0.58+/- 0.32 (rotation). N-way analysis
      of variance (Type III constrained sum of squares, no interaction effects)
      revealed that the relative effects of test speed, pectoral girdle constraint, and
      PMHS anthropometry on the UTS-PG dynamic properties varied per property and
      direction. While more work is needed to verify accuracy in realistic crash
      scenarios, the UTS-PG model system dynamic properties could eventually aid in
      developing integrated anthropomorphic test device (ATD) thoracic spine and
      shoulder components to provide improved head kinematics and belt interaction.

PMID- 23169126
TI  - A comprehensive overview of the frequency and the severity of injuries sustained
      by car occupants and subsequent implications in terms of injury prevention.
AB  - The objective of the paper is to give an overview of the road injuries issues in
      France in the 2010's by determining the frequency and the severity of injuries
      sustained by car occupants, and to infer the implications in terms of vehicule
      safety. Three types of analysis are conducted. First, we present a time series
      analysis at a macro statistical level showing a dramatic decrease of injured and
      fatally injured occupants in passenger cars compared to other modes of road
      transport. Secondly, we propose a descriptive statistical analysis of the
      injuries (frequency and severity) sustained by car occupants, by body regions,
      using the AIS. Finally we propose some insights into the effectiveness of some
      safety features. French National crash census (BAAC) is used for a general
      overview of injury frequencies and raw severity scores (fatal, hospitalized,
      slighty injured) in car crashes. In-depth crash investigations data are used to
      specify the body regions and the severity of the injuries sustained by car
      occupants. Data show that car occupants mortality and morbidity decreased more
      over the last decade than other road modes: -58 % fatalities and -64 %
      hospitalized (compared to -39% and -55% for pedestrians, and -21% and -44% for
      motorcyclists for example). In crashes for which at least one person has been
      injured, 19 % of occupants are uninjured, 49 % of occupants sustain MAIS 1
      injuries, 15 % MAIS2, 8% MAIS 3, and 9 % MAIS 4+. Regardless of seat belt use,
      the body regions most often injured are head, upper and lower extremities and
      thorax. However, at least two third up to 92% of involved persons sustain no
      injury at each of these body regions. The frequency of severe injuries is low,
      often less than 10 % and concern head and thorax mainly. Finally, the frequency
      and severity of injuries decrease for belted occupants in newer cars compared to
      older cars, whatever body regions. The frequency of severe injuries decreased by
      almost 50 % in these newer cars.

PMID- 23169127
TI  - Frailty and injury causation.
AB  - PURPOSE: : The current study will attempt to elucidate whether frailty has a role
      in motor vehicle crash injury causation. METHODS: : The association between
      frailty and injury was studied among Crash Injury Research Engineering Network
      (CIREN) cases. The baseline "physical functioning" (PF) score of the SF-36 was
      used as a marker of frailty (i.e., PF score <75). Frailty associations with ISS
      and occupant, vehicular and crash factors were explored. Frailty association with
      delta V was analyzed among injured (i.e., brain, rib, or femur) belted occupants
      in frontal crashes to establish whether frailty confers a different risk of each
      particular injury. RESULTS: : Frailty occurred in 13.7 % of the cohort (n=1,747).
      Median (q1-q3) ISS was 14.0 (10-22) among the frail and 17.0 (10-24) among the
      non frail (p=0.40). Frailty was significantly associated with advanced age, male
      gender, the presence of co-morbidities, extreme BMIs, frontal and near-side
      crashes and delta V < 45 km/h. Seat belt use and ISS<16 were not associated with
      frailty. Multiple linear regressions, adjusting for age, gender and BMI revealed
      a negative association between frailty and log delta V (coefficient -0.188,
      p=0.04) among those with rib fractures but not among those with brain injuries or
      femur fractures. CONCLUSION: : PF score, a marker of frailty, is associated with
      similar ISS and lower delta V and is independently linked to lower delta V
      thresholds for some injuries (i.e. rib fractures) but not for others (i.e. brain
      injuries and femur fractures). These associations suggest a potential role of
      frailty in injury causation.

PMID- 23169128
TI  - Degree of urbanization and mortality from motor vehicular crashes.
AB  - PURPOSE: : The purpose of this study is to establish whether motor vehicular
      crash (MVC) case fatality varies across different urbanization levels in the USA
      using a representative sample of crashes. METHODS: : Odds ratios (ORs) and 95%
      confidence intervals (CIs) for the association between urbanization level [i.e.,
      central city (CC), suburban (SU) and others (OT)] and mortality were estimated in
      the 1997 - 2010 National Automotive Sampling System Crashworthiness Data System.
      Multiple logistic regression was used to adjust for confounders. Analysis was
      repeated for the occurrence of pre-hospital and hospital deaths. RESULTS: :
      49,040,520 weighted occupants were included in the study. The distribution of
      occupants by urbanization categories was: SU 45%, OT 42%, and CC 13%. Case
      fatality was higher among OT occupants (0.81%) than among SU (0.51%) and CC
      (0.37%) occupants. Similar findings were present for pre-hospital deaths (OT
      0.52%, SU 0.30%, and CC 0.21%) and hospital deaths (OT 0.29%, SU 0.21%, and CC
      0.16%). Multivariate analysis revealed that adjusted odds of death were higher
      for OT cases [OR=1.55 (1.05-2.30)] than the CC. Adjusted odds of death for SU
      (OR=1.05 (0.81-1.37) were not different than CCs. Similar but accentuated
      findings were found for pre-hospital deaths. In contrast, adjusted odds of
      hospital death were not different among the 3 groups. CONCLUSION: : Occupants of
      vehicles crashing in OT (i.e., rural areas and small cities) experience a higher
      likelihood of dying after MVCs than those in CC and SU. Pre-hospital deaths, not
      hospital deaths, are responsible for this disparity.

PMID- 23169129
TI  - Practices, attitudes and perceptions toward road safety in yerevan, republic of
      armenia.
AB  - OBJECTIVES: : To determine knowledge and attitudes regarding traffic safety
      devices, measures, and legislation in the general population in Yerevan, Republic
      of Armenia. METHODS: : We conducted a baseline random digit dial fixed line
      telephone verbal survey of Yerevan households in April 2009 with a follow-up
      survey in May 2010. Survey domains included restraint use, motor vehicle crash
      experiences, and attitudes regarding traffic safety. RESULTS: : In the initial
      survey, of 2137 numbers dialed, 436 persons were reached and 390 (90%) agreed to
      participate. Of survey respondents, 90% percent of household cars had seatbelts,
      while 47% had airbags. Twenty-four percent always or usually wore a seatbelt when
      driving, 21% wore a belt as a passenger. 39% were unaware of child restraints. Of
      the 61% who were aware of child restraints, only 32% had ever used one. A follow
      up survey was conducted one year later after enforcement efforts were increased.
      In the follow-up survey, 81% percent always or usually wore a seatbelt when
      driving, and 69% wore a belt as a passenger. There was no significant increase of
      awareness or use of child restraints in the follow-up survey. CONCLUSIONS: :
      Although cars in Yerevan have seat belts, the majority of drivers and passengers
      prior to the intervention did not use them. Knowledge and use of child restraints
      was poor. The follow-up survey conducted after an enforcement campaign was
      underway in Yerevan showed that improved enforcement greatly increased awareness
      and compliance with current legislation. This study provides vital baseline
      information for the formulation of future policy. It also highlights the need for
      a multi-dimensional road traffic safety initiative through public educational
      campaigns, enforcement of current laws, and development of novel prevention
      policies and regulations.

PMID- 23169130
TI  - Factors affecting ejection risk in rollover crashes.
AB  - Ejection greatly increases the risk of injury and fatality in a rollover crash.
      The purpose of this study was to determine the crash, vehicle, and occupant
      characteristics that affect the risk of ejection in rollovers. Information from
      real world rollover crashes occurring from 2000 - 2010 was obtained from the
      National Automotive Sampling System (NASS) in order to analyze the effect of the
      following parameters on ejection risk: seatbelt use, rollover severity, vehicle
      type, seating position, roof crush, side curtain airbag deployment, glazing type,
      and occupant age, gender, and size. Seatbelt use was found to reduce the risk of
      partial ejection and virtually eliminate the risk of complete ejection. For
      belted occupants, the risk of partial ejection risk was significantly increased
      in rollover crashes involving more roof inversions, light trucks and vans (LTVs),
      and larger occupants. For unbelted occupants, the risk of complete ejection was
      significantly increased in rollover crashes involving more roof inversions, LTVs,
      far side occupants, and higher levels of roof crush. Roof crush was not a
      significant predictor of ejection after normalizing for rollover severity.
      Curtain airbag deployment was associated with reduced rates of partial and
      complete ejection, but the effect was not statistically significant, perhaps due
      to the small sample size (n = 89 raw cases with curtain deployments). A much
      greater proportion of occupants who were ejected in spite of curtain airbag
      deployment passed through the sunroof and other portals as opposed to the
      adjacent side window compared to occupants who were ejected in rollovers without
      a curtain airbag deployment. The primary factors that reduce ejection risk in
      rollover crashes are, in generally decreasing order of importance: seatbelt use,
      fewer roof inversions, passenger car body type, curtain airbag deployment, near
      side seating position, and small occupant size.

PMID- 23169132
TI  - Influence of injury risk thresholds on the performance of an algorithm to predict
      crashes with serious injuries.
AB  - This paper presents methods to estimate crash injury risk based on crash
      characteristics captured by some passenger vehicles equipped with Advanced
      Automatic Crash Notification technology. The resulting injury risk estimates
      could be used within an algorithm to optimize rescue care. Regression analysis
      was applied to the National Automotive Sampling System / Crashworthiness Data
      System (NASS/CDS) to determine how variations in a specific injury risk threshold
      would influence the accuracy of predicting crashes with serious injuries. The
      recommended thresholds for classifying crashes with severe injuries are 0.10 for
      frontal crashes and 0.05 for side crashes. The regression analysis of NASS/CDS
      indicates that these thresholds will provide sensitivity above 0.67 while
      maintaining a positive predictive value in the range of 0.20.

PMID- 23169133
TI  - The effect of a low-speed automatic brake system estimated from real life data.
AB  - A substantial part of all traffic accidents involving passenger cars are rear-end
      collisions and most of them occur at low speed. Auto Brake is a feature that has
      been launched in several passenger car models during the last few years. City
      Safety is a technology designed to help the driver mitigate, and in certain
      situations avoid, rear-end collisions at low speed by automatically braking the
      vehicle.Studies have been presented that predict promising benefits from these
      kinds of systems, but few attempts have been made to show the actual effect of
      Auto Brake. In this study, the effect of City Safety, a standard feature on the
      Volvo XC60 model, is calculated based on insurance claims data from cars in real
      traffic crashes in Sweden. The estimated claim frequency of rear-end frontal
      collisions measured in claims per 1,000 insured vehicle years was 23% lower for
      the City Safety equipped XC60 model than for other Volvo models without the
      system.

PMID- 23169134
TI  - Safety Changes in the US Vehicle Fleet since Model Year 1990, Based on NASS Data.
AB  - Based on the National Automotive Sampling System Crashworthiness Data System
      since the 1988-1992 model years, there has been a reduction in the MAIS 3+ injury
      rate and the Mean HARM for all crash modes. The largest improvement in vehicle
      safety has been in rollovers. There was an increase in the rollover injury rate
      in the 1993-1998 model year period, but a reduction since then. When comparing
      vehicles of the model year 1993 to 1998 with later model vehicles, the most
      profound difference was the reduction of rollover frequency for SUV's - down more
      than 20% when compared to other crash modes. When considering only model years
      since 2002 the rollover frequency reduction was nearly 40%. A 26% reduction in
      the rate of moderate and serious injuries for all drivers in rollovers was
      observed for the model years later than 1998. The overall belt use rate for
      drivers of late model vehicles with HARM weighted injuries was 62% - up from 54%
      in earlier model vehicles. However, in rollover crashes, the same belt use rate
      lagged at 54%.

PMID- 23169131
TI  - Differences in thoracic injury causation patterns between seat belt restrained
      children and adults.
AB  - The objective of this research was to delineate age-based differences in specific
      thoracic injury diagnoses for seat belt restrained rear seat occupants and
      describe the associated injury causation in order to provide insight into how the
      load of the seat belt is transferred to occupants of various sizes. Using data
      from the Crash Investigation Research and Engineering Network (CIREN), 20 cases
      of rear seated, lap and shoulder belt restrained occupants with AIS2+ thoracic
      injuries in frontal crashes were reviewed. Seven were children and adolescents
      age 8-15 years, 5 were 16-24 years, 3 were 25-54 years, and 5 were 55+ years. Six
      of the seven 8-15 year olds sustained injuries to the lung in the form of
      pulmonary contusion or pneumothorax. Only three of the seven sustained a skeletal
      (sternum or rib) fracture; only one of these three involved multiple ribs
      bilaterally. In contrast, four of the five 16-24 year olds sustained at least one
      rib fracture - often multiple and bilateral. The adult cohort (25+ years) was
      involved in predominantly more minor crashes; however they all sustained complex
      rib fractures - seven of the eight involved multiple ribs, four of the eight were
      also bilateral. Belt compression - either from the shoulder belt or the lap belt 
      was identified as the primary cause of the thoracic injuries. Often, there was
      clear evidence of the location of belt loading from AIS 1 chest contusions or
      abrasions. These findings have implications for age-based thoracic injury
      criteria suggesting that that different metrics may be needed for different age
      groups.

PMID- 23169135
TI  - Impact and injury patterns in between-rails frontal crashes of vehicles with good
      ratings for frontal crash protection.
AB  - This research investigated (1) what are the key attributes of the between-rail,
      frontal crash, (2) what are the types of object contacted, and (3) what is the
      type of resulting trauma. The method was to study with both weighted and in-depth
      case reviews of NASS-CDS crash data with direct damage between the longitudinal
      rails in frontal crashes. Individual case selection was limited to belted
      occupants in between-rail, frontal impacts of good-rated, late-model vehicles
      equipped with air bags.This paper evaluates the risk of trauma for drivers in
      cars and LTVs in between-rail, frontal crashes, and suggests the between-rail
      impact is more dangerous to car drivers. Using weighted data-representing 227,305
      tow-away crashes-the resulting trauma to various body regions was analyzed to
      suggest greatest injury is to the chest, pelvis/thigh/knee/leg, and foot/ankle.
      This study analyzed the type of object that caused the direct damage between the
      rails, including small tree or post, large tree or pole, and another vehicle; and
      found that the struck object was most often another vehicle or a large tree/pole.
      Both the extent of damage and the occupant compartment intrusion were explored,
      and suggest that 64% of the serious injuries are associated with increasing
      intrusion. Individual NASS cases were reviewed to gain a deeper understanding of
      the mechanical particulars in the between-rail crash.

PMID- 23169136
TI  - Injury risk functions in frontal impacts using data from crash pulse recorders.
AB  - Knowledge of how crash severity influences injury risk in car crashes is
      essential in order to create a safe road transport system. Analyses of real-world
      crashes increase the ability to obtain such knowledge.The aim of this study was
      to present injury risk functions based on real-world frontal crashes where crash
      severity was measured with on-board crash pulse recorders.Results from 489
      frontal car crashes (26 models of four car makes) with recorded acceleration-time
      history were analysed. Injury risk functions for restrained front seat occupants
      were generated for maximum AIS value of two or greater (MAIS2+) using multiple
      logistic regression. Analytical as well as empirical injury risk was plotted for
      several crash severity parameters; change of velocity, mean acceleration and peak
      acceleration. In addition to crash severity, the influence of occupant age and
      gender was investigated.A strong dependence between injury risk and crash
      severity was found. The risk curves reflect that small changes in crash severity
      may have a considerable influence on the risk of injury. Mean acceleration,
      followed by change of velocity, was found to be the single variable that best
      explained the risk of being injured (MAIS2+) in a crash. Furthermore, all three
      crash severity parameters were found to predict injury better than age and
      gender. However, age was an important factor. The very best model describing
      MAIS2+ injury risk included delta V supplemented by an interaction term of peak
      acceleration and age.

PMID- 23169137
TI  - Thoracolumbar spine fractures in frontal impact crashes.
AB  - There is currently no injury assessment for thoracic or lumbar spine fractures in
      the motor vehicle crash standards throughout the world. Compression-related
      thoracolumbar fractures are occurring in frontal impacts and yet the mechanism of
      injury is poorly understood. The objective of this investigation was to
      characterize these injuries using real world crash data from the US-DOT-NHTSA
      NASS-CDS and CIREN databases. Thoracic and lumbar AIS vertebral body fracture
      codes were searched for in the two databases. The NASS database was used to
      characterize population trends as a function of crash year and vehicle model
      year. The CIREN database was used to examine a case series in more detail. From
      the NASS database there were 2000-4000 occupants in frontal impacts with thoracic
      and lumbar vertebral body fractures per crash year. There was an increasing trend
      in incidence rate of thoracolumbar fractures in frontal impact crashes as a
      function of vehicle model year from 1986 to 2008; this was not the case for other
      crash types. From the CIREN database, the thoracolumbar spine was most commonly
      fractured at either the T12 or L1 level. Major, burst type fractures occurred
      predominantly at T12, L1 or L5; wedge fractures were most common at L1. Most
      CIREN occupants were belted; there were slightly more females involved; they were
      almost all in bucket seats; impact location occurred approximately half the time
      on the road and half off the road. The type of object struck also seemed to have
      some influence on fractured spine level, suggesting that the crash deceleration
      pulse may be influential in the type of compression vector that migrates up the
      spinal column. Future biomechanical studies are required to define
      mechanistically how these fractures are influenced by these many factors.

PMID- 23169138
TI  - Kinematic Comparison of the Hybrid III and Q-Series Pediatric ATDs to Pediatric
      Volunteers in Low-Speed Frontal Crashes.
AB  - Previous research has suggested that the rigid pediatric ATD spine may not
      adequately represent the relatively mobile, multi-segmented spine of the child
      and thus may lead to important differences in the head trajectory of the ATD
      relative to a human. Recently we compared the responses of size-matched child
      volunteers to the Hybrid III 6-year-old ATD in low-speed frontal sled tests,
      illustrating differences in head, spinal, and pelvic kinematics as well as
      seating environment reaction loads. This paper expands this line of work to
      include comparisons between size-matched restrained child volunteers to the
      Hybrid III 10-year-old and the Q-series 6 and 10-year-old ATDs tested in the same
      low speed frontal environment. A 3-D near-infrared video target tracking system
      quantified the position of markers on the ATDs and volunteers(head top, nasion,
      external auditory meatus, C4, T1, and pelvis). Angular velocity of the head, seat
      belt forces, and reaction loads on the seat pan and foot rest were also measured.
      The Hybrid III 6 and Q6 exhibited significantly greater belt reaction loads
      compared to the pediatric volunteers, which exhibited greater seat pan shear.
      Compared to children, the Hybrid III 6 exhibited increased head rotation and
      similar head top and pelvic excursion, whereas the Q6 exhibited reductions in all
      three metrics. The Hybrid III 10 and Q10 ATDs exhibited reaction loads similar to
      the volunteers; however, excursions and head rotation were significantly reduced
      compared to volunteers. All pediatric ATDs exhibited significant reductions in C4
      and T1excursions compared to the volunteers, likely due to the rigidity of the
      ATD thoracic spine. These analyses provide insight into aspects of ATD
      biofidelity in low-speed crash environments and illustrate differences in
      responses of the Hybrid III and Q-series pediatric ATDs.

PMID- 23169139
TI  - Homogenization of vehicle fleet frontal crash pulses from 2000-2010.
AB  - Full-scale vehicle crash tests are performed globally to assess vehicle structure
      and restraint system performance. The crash pulse, captured by accelerometers
      mounted within the occupant compartment, measures the motion of the vehicle
      during the impact event. From an occupant's perspective, the crash pulse is the
      inertial event to which the vehicle's restraint systems must respond in order to
      mitigate the forces and accelerations that act on a passenger, and thus reduce
      injury risk. The objective of this study was to quantify the characteristics of
      crash pulses for different vehicle types in the contemporary North American
      fleet, and delineate current trends in crash pulse evolution. NHTSA and Transport
      Canada crash test databases were queried for full-frontal rigid barrier crash
      tests of passenger vehicles model year 2000-2010 with impact angle equaling zero
      degrees. Acceleration-time histories were analyzed for all accelerometers
      attached to the vehicle structure within the occupant compartment. Custom
      software calculated the following crash pulse characteristics (CPCs): peak
      deceleration, time of peak deceleration, onset rate, pulse duration, and change
      in velocity. Vehicle body types were classified by adapting the Highway Loss Data
      Institute (HLDI) methodology, and vehicles were assigned a generation start year
      in place of model year in order to more accurately represent structural change
      over time. 1094 vehicle crash tests with 2795 individual occupant compartment
      mounted accelerometers were analyzed. We found greater peak decelerations and and
      shorter pulse durations across multiple vehicle types in newer model years as
      compared to older. For midsize passenger cars, large passenger cars, and large
      SUVs in 56 km/h rigid barrier tests, maximum deceleration increased by 0.40,
      0.96, and 1.57 g/year respectively, and pulse duration decreased by 0.74, 1.87,
      and 2.51 ms/year. We also found that the crash pulse characteristics are becoming
      more homogeneous in the modern vehicle fleet; the range of peak deceleration
      values for all vehicle classes decreased from 17.1 g in 1997-1999 generation
      start years to 10.7 g in 2009-2010 generation years, and the pulse duration range
      decreased from 39.5 ms to 13.4 ms for the same generation year groupings. This
      latter finding suggests that the designs of restraint systems may become more
      universally applicable across vehicle body types, since the occupant compartment
      accelerations are not as divergent for newer vehicles.

PMID- 23169148
TI  - Effects of low concentrations of regorafenib and sorafenib on human HCC cell AFP,
      migration, invasion, and growth in vitro.
AB  - Sorafenib was shown in clinical trial to enhance survival in hepatocellular
      carcinoma (HCC) patients, but with minimal tumor shrinkage. To correlate several
      indices of HCC growth at various drug concentrations, HCC cells were grown in
      various low concentrations of two multikinase inhibitors, regorafenib (Stivarga)
      and sorafenib (Nexavar) and their effects were examined on alpha-fetoprotein
      (AFP), cell growth, migration, and invasion. In two AFP positive human HCC cell
      lines, AFP was inhibited at 0.1-1 uM drug concentrations. Cell migration and
      invasion were also inhibited at similar low drug concentrations. However, 10-fold
      higher drug concentrations were required to inhibit cell growth in both AFP
      positive and negative cells. To investigate this concentration discrepancy of
      effects, cells were then grown for prolonged times and sub-cultured in low drug
      concentrations and then their growth was re-tested. The growth in these drug
      exposed cells was found to be slower than cells without prior drug exposure and
      they were also more sensitive to subsequent drug challenge. Evidence was also
      found for changes in cell signaling pathways in these slow-growth cells. Low
      multikinase inhibitor concentrations thus modulate several aspects of HCC cell
      biology.

PMID- 23169140
TI  - IL-21 promotes the production of anti-DNA IgG but is dispensable for kidney
      damage in lyn-/- mice.
AB  - The autoimmune disease systemic lupus erythematosus is characterized by loss of
      tolerance to nuclear Ags and a heightened inflammatory environment, which
      together result in end organ damage. Lyn-deficient mice, a model of systemic
      lupus erythematosus, lack an inhibitor of B-cell and myeloid cell activation.
      This results in B-cell hyper-responsiveness, plasma cell accumulation,
      autoantibodies, and glomerulonephritis (GN). IL-21 is associated with
      autoimmunity in mice and humans and promotes B-cell differentiation and class
      switching. Here, we explore the role of IL-21 in the autoimmune phenotypes of
      lyn(-/-)  mice. We find that IL-21 mRNA is reduced in the spleens of lyn(-/-) IL
      6(-/-)  and lyn(-/-) Btk(lo)  mice, neither of which produce pathogenic
      autoantibodies or develop significant GN. While IL-21 is dispensable for plasma
      cell accumulation and IgM autoantibodies in lyn(-/-)  mice, it is required for
      anti-DNA IgG antibodies and some aspects of T-cell activation. Surprisingly, GN
      still develops in lyn(-/-) IL-21(-/-)  mice. This likely results from the
      presence of IgG autoantibodies against a limited set of non-DNA Ags. These
      studies identify a specific role for IL-21 in the class switching of anti-DNA B
      cells and demonstrate that neither IL-21 nor anti-DNA IgG is required for kidney
      damage in lyn(-/-)  mice.

PMID- 23169150
TI  - Current controversies in pediatric urologic robotic surgery.
AB  - PURPOSE OF REVIEW: Minimally invasive surgeries such as conventional laparoscopic
      surgery and robotic assisted laparoscopic surgery (RALS) have significant
      advantages over the traditional open surgical approach including lower pain
      medication requirements and decreased length of hospitalization. However, open
      surgery has demonstrated better success rates and shorter surgery time when
      compared to the other modalities. Currently, it is unclear which approach has
      better long-term clinical outcomes, greater benefits and less cost. RECENT
      FINDINGS: There are limited studies in the literature comparing these three
      different surgical approaches. In this review, we will evaluate the advantages
      and disadvantages of RALS compared to conventional laparoscopic surgery and open
      surgery for commonly performed pediatric urological procedures such as
      pyeloplasty, ureteral reimplantation, complete and partial nephrectomy, bladder
      augmentation and creation of continent catheterizable channels. SUMMARY: Although
      it is not yet possible to demonstrate the superiority of one single surgical
      modality over another, RALS has been shown to be feasible, well tolerated and
      advantageous in reconstructive urological procedures. With experience, the
      outcomes of RALS are improving, justifying its usage. However, cost remains a
      significant issue, limiting the accessibility of RALS, which in the future may
      improve with market competition and device innovation.

PMID- 23169149
TI  - Investigation of different boundary treatment methods in Monte-Carlo simulations
      of diffusion NMR.
AB  - PURPOSE: To enrich and develop more convenient and effective boundary treatment
      method in Monte-Carlo simulation of restricted diffusion nuclear magnetic
      resonance. METHODS: The conventional approach used in treating boundary behaviors
      of restricted diffusion is the elastic boundary reflection. Because random walk
      is not dynamic process, other boundary treatments such as inelastic reflection
      are acceptable and probably simplify the programming of diffusion nuclear
      magnetic resonance simulation. The present study simulated the pulse gradient
      spin echo nuclear magnetic resonance by employing three boundary models, i.e.,
      the elastic boundary reflection, the non-elastic boundary reflection, and the
      equal-step-length random leap. Their effects on precision, convergence, and
      calculation efficiency were investigated, as well as the effects of non-fixed
      boundary reflection step-length drawn from a Gaussian distribution in barrier
      crossing steps. RESULTS: The results show no obvious difference in convergences
      and precisions for different methods when the relative step-length is
      sufficiently small. Compared with the traditional approach, the required
      computation time of the latter two was reduced in some degree. CONCLUSION:
      Boundary treatments based on inelastic reflection are a feasible choice in Monte
      Carlo simulation of nuclear magnetic resonance, and in comparison with the
      conventional approach, it not only renders programming more convenience but also
      possibly lead to higher calculating efficiency.

PMID- 23169151
TI  - Anatomic and technical considerations for optimizing recovery of urinary function
      during robotic-assisted radical prostatectomy.
AB  - PURPOSE OF REVIEW: The advent of robotic-assisted radical prostatectomy purported
      fewer complications including postprostatectomy incontinence (PPI). PPI is
      associated with worse quality of life. We evaluate recently reported robot
      assisted radical prostatectomy surgical techniques aimed at limiting PPI,
      describe their anatomic basis and summarize their outcomes. RECENT FINDINGS: RARP
      techniques to reduce PPI include bladder neck preservation, bladder neck
      reconstruction, urethral length preservation, periurethral suspension stitch,
      posterior reconstruction, combined anterior and posterior reconstruction,
      preservation of the endopelvic fascia, complete anterior preservation, selective
      suturing of dorsal venous complex and nerve sparing approach. Outcomes of
      reconstructive techniques seem to be conflicting, whereas outcomes of techniques
      aiming to preserve the native urinary continence system seem to hasten urinary
      function recovery. However, few of these techniques have been shown to affect
      long-term urinary continence. SUMMARY: Surgical techniques preserving the natural
      urinary continence mechanism appear to improve short-term urinary continence,
      whereas techniques reconstructing pelvic anatomy have mixed results. The search
      for the ideal technique to minimize PPI remains hampered by the lack of
      prospective multi-institutional studies and the long-term follow up. Although
      reconstructive techniques are safe with few drawbacks, meticulous surgical
      technique and preservation of the natural continence mechanism should remain the
      mainstay of PPI prevention.

PMID- 23169152
TI  - Anatomic and technical considerations for optimizing recovery of sexual function
      during robotic-assisted radical prostatectomy.
AB  - PURPOSE OF REVIEW: Although cure of prostate cancer is the primary goal of
      radical prostatectomy, preserving erectile function is also tantamount, given the
      indolent clinical course of most prostate cancers, particularly low-risk disease.
      In order to optimize postprostatectomy erectile function during a robotic
      assisted radical prostatectomy, there must be a detailed understanding of pelvic
      anatomy to recognize the optimal nerve-sparing plane and technical finesse to
      minimize stretch injury to the neurovascular bundle. RECENT FINDINGS: The
      magnified, well illuminated robotic-operative field coupled with less blood loss
      has paralleled greater understanding of the periprostatic 'fascial' planes,
      leading to differentiation of intrafascial versus interfascial nerve-sparing
      approaches. However, refinement of tissue handling during nerve-sparing to
      minimize lateral displacement of the neurovascular bundle and attenuate
      neurapraxia enables earlier and better recovery of erectile function. SUMMARY:
      The critical maneuvers to preserving erectile function are atraumatic dissection
      of the prostate away from the optimal nerve-sparing plane to maximally preserve
      nerve fibers while minimizing neurapraxia. Therefore, attaining these principles
      involves a conceptual paradigm shift from 'radical' prostatectomy to neurosurgery
      of the prostate.

PMID- 23169153
TI  - Different mechanisms underlying changes in excitability of peripheral nerve
      sensory and motor axons in multiple sclerosis.
AB  - INTRODUCTION: Subtle involvement of peripheral nerves may occur in multiple
      sclerosis. Motor excitability studies have suggested upregulation of slow K+
      currents, probably secondary to altered motoneuron properties resulting from the
      central lesion. This study concentrates on sensory axons. METHODS: Excitability
      of median nerve axons at the wrist was studied in 26 patients. RESULTS: Sensory
      recordings were possible in 22 patients, and reduced superexcitability was the
      sole abnormality. There was no evidence for changes in membrane potential or
      demyelination. The decrease was significant in patients taking immunomodulatory
      therapy. These findings could be reproduced in a computer model by changing the
      gating of fast K+ channels. Motor axon findings were consistent with previously
      reported increased slow K+ current. CONCLUSIONS: The sensory findings differ from
      motor findings. They can be explained by a humoral factor, possibly cytokines,
      which can penetrate the paranode and have been documented to alter the gating of
      K+ channels.

PMID- 23169155
TI  - [Evaluation of serological results of patients with suspected Toxoplasmosis
      admitted to the medical parasitology laboratory of Celal Bayar University
      Hospital between 2006-2010].
AB  - OBJECTIVE: The aim of this study is to determine the serological results of
      patients with suspected toxoplasmosis who were admitted to the Medical
      Parasitology Laboratory of Celal Bayar University Hospital in Manisa between 2006
      and 2010. METHODS: Anti-Toxoplasma gondii IgG and IgM antibodies were
      investigated by IFAT, IgG ELISA, and IgM Capture ELISA in 2815 patients. IgG
      avidity tests were also performed in cases with both IgG and IgM seropositivity.
      RESULTS: Only IgG, only IgM and both IgG and IgM seropositivity were detected in
      657 (23.3%), 4 (0.1%) and 6 (0.2%) cases respectively among 2815 patients. Anti
      T. gondii IgG seropositivity was mostly found in patients [21.2% (n=139)] who
      consume raw meat. IgG seroprevalence was found to be statistically higher in the
      15-49 age group than the 0-14 age group (p < 0.05). Decrease in the prevalence of
      anti- T. gondii IgG seropositivity in 2010 was found to be statistically
      significant considering the five years period (p < 0.001). CONCLUSION: Raw meat
      consumption was detected as the most important risk factor in Toxoplasma
      infection. A decrease in anti-T. gondii IgG antibodies was detected in recent
      years considering the five years' serologic data, but toxoplasmosis remains
      important as a public health problem in Manisa.

PMID- 23169154
TI  - [Investigation of anti-Toxoplasma gondii IgG and IgM antibodies in beta
      thalassemia major patients in Aydin province].
AB  - OBJECTIVE: Blood transfusion therapy for Thalassaemia patients may cause
      transmission of some infectious agents to the recipients. As Toxoplasma gondii is
      a transfusion-transmitted parasite, we aimed to investigate anti-Toxoplasma
      antibodies. METHODS: We arranged two groups: patients and controls. There were 36
      Thalassaemia cases in the patient group. The control group also included 36
      healthy people (of the same ages and gender) who were selected by the one-to-one
      mapping method. Mean age was 18.1 +/- 8.3 (4-35). Toxoplasma gondii IgG and IgM
      antibodies were analyzed by the Enzyme-Linked Immunosorbant Assay (ELISA).
      RESULTS: We determined parasite-specific Toxoplasma gondii IgG antibodies in 7
      (19.4%) and borderline levels of IgM antibody in 2 Thalassaemia major cases
      (5.5%). In the control group, parasite-specific IgG antibody was found in 5 cases
      (14%). Serum samples of patients with borderline levels were analyzed with an
      avidity test and were found to have high avidity. There were no significant
      differences between patient and control groups when considering the presence of
      anti-Toxoplasma IgG antibodies (p=0.752). CONCLUSION: Although there is no
      significant statistical difference, we suggest that blood transfusion donors
      should be investigated for infectious agents such as Toxoplasma gondii.

PMID- 23169156
TI  - [Research to investigate human cystic echinococcosis with ultrasound and
      serologic methods and educational studies in different provinces of
      Aydin/Turkey].
AB  - OBJECTIVE: Cystic echinococcosis (CE) is particularly prevalent in rural areas
      where domestic animal breeding is common. We planned to investigate the CE among
      the 7-88 years old inhabitants of (n=209) four villages in the Aydin district, by
      a portable ultrasound scanner (US) and with serologic methods. METHODS:
      Participants were assessed by ultrasound and sera samples were tested for anti-E.
      granulosus antibodies by serological tests (ELISA and IHA). A questionnaire was
      given to the participants in order to assess their knowledge about the disease.
      RESULTS: Hepatic CE was detected in one case (0.47%) by US, while 24 (11.48%) and
      28 (13.39%) cases were found to be seropositive for CE by ELISA and IHA,
      respectively. With both tests, in 9 participants (4.3%), parasite-specific
      antibodies were detected. According to questionnaire results, 84.22% of the
      participants were found to have no knowledge about the disease. Only 15.21% of
      the dog owners were giving anti-parasite drugs to their dogs. CONCLUSION: This
      study is one of the small number of community-based studies about CE performed in
      Turkey, in which US was applied. Our results suggest that we need national
      control programs including a multi-sectorial collaboration to eradicate
      hydatidosis and effective actions to control cystic echinococcosis.

PMID- 23169157
TI  - [Incidence of intestinal parasites detected in the Department of Parasitology in
      Celal Bayar University Hospital between 2006 and 2010].
AB  - OBJECTIVE: Results of 17.711 patien admitted to the Department of Parasitology in
      Celal Bayar University Hospital for parasitological stool examination between
      January 2006 and December 2010 were evaluated. METHODS: All stool samples were
      examined with wet mounts, formalin ethyl acetate concentration and trichrome
      staining methods. In addition, cellophane tape preparations from 5952 patients
      were evaluated. RESULTS: Intestinal parasites were detected in 2337 (13.12%) of
      17.711 patients who were admitted during a five year period. The highest parasite
      infected individual ratio (16.69%) was found in 2008. The most frequently
      identified intestinal parasites were Blastocystis spp. 1353 (7.64%) and Giardia
      intestinalis 348 (1.96%) in stool samples, with Enterobius vermicularis 253
      (4.25%) in cellophane tape preparations. Two or more parasites were detected in
      158 (6.76%) of the positive cases. The mean age of persons identified as having a
      parasite was 21.9. Parasite incidence was 10.7% in females, and 13.6% in males (p
      < 0.001). The highest ratio was 23.8% in patients who lived in rural areas when
      all positive cases were evaluated in terms of settlement areas. CONCLUSION: While
      Blastocystis spp., E. vermicularis and G. intestinalis were the most frequently
      detected intestinal parasites in our province, intestinal parasites still remain
      important despite advances in infrastructure in recent years.

PMID- 23169158
TI  - [The prevalence of liver trematodes in equines in different cities of Turkey].
AB  - OBJECTIVE: This study was carried out between March 2004- April 2005 to determine
      the prevalance of liver trematode infections of equids in different cities of
      Turkey. METHODS: A total of 117 equids (72 horses, 39 donkeys and 6 mules) in
      Ankara were examined for liver parasites after the slaugthering process. On the
      other hand, a total of 620 feces of horses in Bursa, Gemlik, Malatya, Eskisehir
      and Ankara provinces were detected for determining liver trematodes in live
      equines. The fecal samples of horses were examined for liver fluke infection by
      Benedect's sedimentation methods. RESULTS: Of these 117 equids, 6 equids (5.1%)
      were infected with liver flukes. The liver flukes were found only in donkeys.
      Infection rates were found to be Fasciola hepatica 2.6%, Dicrocoelium dendriticum
      12.8% in donkeys.Trematode eggs were encountered in these horses. The
      distribution of liver fluke infections was found to be very low. For this reason,
      the importance of the results for the groups of different age (young-old) and sex
      (male-female) were not determined. CONCLUSION: This study determinated the
      prevalance of the liver trematodes to be low in the equines, higher in donkeys
      than in horses and no clinical signs due to the number of parasites which cause
      helminthosis.

PMID- 23169159
TI  - [Knowledge, attitudes, and behavior of people living in rural areas of Erzurum
      about Crimean-Congo hemorrhagic fever].
AB  - OBJECTIVE: After 2002 more and more Crimean-Congo Hemorrhagic Fever (CCHF) cases
      have been reported and it has become a major public health problem in Turkey. In
      order to fight CCHF, it is important to inform the public and direct them towards
      appropriatet attitudes and behavior. Therefore assessment of the effectiveness of
      health education in the community is essential. METHODS: A research was carried
      out for this purpose in the province of Erzurum between May 2010 and September
      2010 through a survey. RESULTS: The results depicted that the majority of
      participants have knowledge that CCHF transmitted by ticks and they should be
      removed as soon as possible from the body through safe methods. However, in terms
      of correct attitude and behavior, women were found to have a lower level compared
      with men. CONCLUSION: The training of health workers and an increase in the
      efforts to make the community, especially the women, aware of this problem is
      ugently needed.

PMID- 23169160
TI  - Laboratory evaluation of the effect of Egyptian native plants against some
      parasitic vectors.
AB  - OBJECTIVE: Four plant extracts possessing molluscicidal and insecticidal efficacy
      were evaluated under laboratory conditions versus Biomphalaria alexandrina,
      Lymnea cailliaudi snails, their egg masses and Culex pipiens larvae. These
      extracts included Grape seed, Eucalyptus, Pomegranate, Verbesina alcoholic
      extracts, as well as Eucalyptus oil. METHODS: Different mortalities in the
      exposed vectors were recorded due to the four plant extracts using different
      concentrations and exposure time. RESULTS: Total snail mortality LC < sub > 100 <
      /sub > was (100 ppm/12-24h) for Grape seed, (200 ppm/18-24h) for Eucalyptus, (100
      ppm/12-18h) for Pomegranate, (100-200 ppm/24h) for Verbesina alcoholic extracts
      and (100-200 ppm/12h) for Eucalyptus oil. However, only Eucalyptus, Verbesina
      alcoholic extracts and Eucalyptus oil revealed snail ovicidal effects. LC < sub >
      100 < /sub > was (100-200 ppm/24h), (100-200 ppm/24h) & (100-200 ppm/12-48h)
      respectively. Moreover, the same plant extracts were able to induce total Culex
      pipiens larvicidal mortality, LC < sub > 100 < /sub > was (200 ppm/48h). However,
      Grape seed and Pomegranate alcoholic extracts did not induce either snail
      ovicidal or Culex pipiens larvicidal total mortalities. Activities of the studied
      plant extracts were considered using reference molluscicidal (Copper sulfate) and
      insecticidal (Temephos) substances. CONCLUSION: Egyptian native plants continue
      to provide a wealth of potential sources for biologically active agents that may
      have a promising role in the production of safe, biodegradable eco-friendly and
      natural molluscicidal and insecticidal agents.

PMID- 23169161
TI  - Egg laying site and oviposition pattern of two Phthirapteran species parasitizing
      red whiskered Bulbul (Pycnonotus jocosus).
AB  - OBJECTIVE: Present study was performed to record the oviposition and egg laying
      pattern of two phthirapteran species infesting red whiskered Bulbul. METHODS: The
      number of egg laid by each species on different parts of body was recorded by
      direct observation under stereozoom binocular microscope. Feathers bearing egg
      were subjected to SEM to observe the pattern of egg laying. RESULTS: The maximum
      percentage of egg of the ischnoceran louse, Brueelia guldum were recorded on
      feather of back region, followed by neck and breast. The amblyceran louse,
      Menacanthus eurysternus prefers to lay eggs mainly on neck, head and nape
      feathers. CONCLUSION: The ischnoceran louse, Brueelia guldum exhibits widespread
      oviposition sites while amblyceran louse, Menacanthus eurysternus shows
      restricted oviposition sites on the host body.

PMID- 23169162
TI  - [The first record of Ornithocheyletia hallae Smiley, 1970 (Acariformes:
      Actinedida: Cheyletidae) and its prevalance on Pseudolynchia canariensis
      (Mcquart, 1840) (Diptera: Pupipara: Hippoboscidae) in Turkey].
AB  - OBJECTIVE: This study was performed to detect acar species and their prevalence
      on Pseudolynchia canariensis. METHODS: The pigeons were treated with a carbamate
      group insectiside in a carton box, kept there for 15-20 minutes and the
      ectoparasites which fell off the birds onto the bottom of the box collected in a
      petri dishes. The P. canariensis specimens were examined macroscopically and
      microscopically for lice and acari. The acar samples were mounted on the slides
      in Canada balsam after being transparented and identified as to species. RESULTS:
      A total of 42 P. canariensis specimens were collected from the pigeon. 15
      (35.71%) were found to be infested with the acari, while no louse specimen was
      detected. Forty-six acari specimens were collected from the P. canariensis and
      they were identified as Ornithocheyletia hallae Smiley, 1970. CONCLUSION: It was
      detected that approximately one third of P. canariensis were infested with
      Ornithocheyletia hallae, and this acar species was recorded for the first time in
      Turkey in this study.

PMID- 23169163
TI  - Metazoan parasites of the common carp (Cyprinus carpio L., 1758) from Tahtali Dam
      Lake (Izmir).
AB  - OBJECTIVE: The aim of this study was identification of the parasites of the
      common carp from Tahtali Dam Lake. METHODS: The fish were transported live to the
      laboratory. They were investigated for ectoparasites and endoparasites. The
      parasite specimens were fixed and identified. RESULTS: During the study, 47
      common carp were caught monthly and 3 species of metazoan parasites were found:
      Dactylogyrus extensus (Monogenea), Contracaecum sp. larvae (Nematoda) and Lernaea
      cyprinacea (Crustacea). CONCLUSION: The parasite species were new records for
      Tahtali Dam Lake. Contracaecum sp. larvae were recorded for the first time from
      Cyprinus carpio in Turkey.

PMID- 23169164
TI  - Description of Rhynchocystis silvae sp. nov (Apicomplexa: Eugregarinida) from
      Metaphire peguana Rosa (1890) of Dhaka, Bangladesh.
AB  - OBJECTIVE: Biodiversity studies in search of endoparasitic acephaline gregarines
      of earthworms revealed a new species under the genus Rhynchocystis Hesse, 1909.
      METHODS: The species has been obtained from the seminal vesicles of the
      earthworm, Metaphire peguana. The parasite was identified using standard
      methodology. RESULTS: Gamonts are solitary, elongated with a conical, enlarged
      head and blunt posterior end. The mature gamont measures 419.90- 430.95 (425.05+/
      4.70) MUm in length and the width at the widest portion is 44.2-50.83 (47.88+/
      2.85) MUm and 15.47-17.68 (16.50+/-1.14) MUm in the posterior end. The nucleus is
      elongated and positioned at the posterior end. The nucleus measures 17.68-22.01
      (19.74+/-1.95) MUmx11.05- 15.47 (13.40+/-1.95) MUm. The measurement of the mucron
      is 13.26-17.68 (15.47+/-1.86) MUmx17.68-22.1 (19.44+/-1.71) MUm. Gametocysts are
      ovoid with two unequal sized gametocytes. The gametocyst measures 95.03-97.24
      (96.20+/-1.14) MUmx77.35-81.77 (79.56+/-1.86) MUm. Large and small gametocytes
      measure 57.46-61.88 (59.81+/-1.76) MUmx70.72-75.14 (72.48+/-1.71) MUm and 30.94
      37.57 (34.47+/-2.74) MUmx61.88-66.3 (64.38+/-1.84) MUm respectively. Oocysts are
      biconical, measuring 11.05-15.47 (12.81+/-1.71) MUmx6.63-8.84 (7.70+/-1.20) MUm.
      CONCLUSION: A new gregarine parasite species is described.

PMID- 23169165
TI  - [Microscopic examination of vaginal discharge specimens for Trichomonas vaginalis
      and other micro-organisms in 18-45 age group women].
AB  - OBJECTIVE: Trichomonas vaginalis is a protozoon that causes trichomoniasis which
      is characterised by a foamy yellowish odorous discharge and superficial defects
      and necrotic ulcers in vaginal mucosa. Trichomoniasis is transmitted from human
      to human by sexual contact and can be seen in almost every part of the world. The
      aim of this study was to determine the incidence of Trichomonas vaginalis in 18
      45 years age group women with vaginal discharge complaints who applied to the
      Gynaecology Outpatient Clinic of Konya Social Insurance Instution Hospital during
      September 1-December 15 2003. METHODS: Samples were taken from posterior fornix
      of the vagina with the aid of a speculum and sterile cotton swabs. All the
      samples were examined by wet mount preparations, Gram and Giemsa staining method
      under the light microscope. RESULTS: Of seventy samples 6 (9%) were positive for
      Trichomonas vaginalis, 9 (13%) for Gardnerella vaginalis, one for Mobiluncus spp.
      and 11 (16%) for Candida spp. CONCLUSION: It is possible to say that, in spite of
      a definite diagnosis of trichomoniasis made by cultivation method, examining the
      vaginal smear by direct microscope also has an important role in the diagnosis of
      infection. Direct microscopic examination will help in deciding whether to begin
      the treatment of trichomoniasis.

PMID- 23169166
TI  - A pediculid case: autosensitization dermatitis caused by pediculosis capitis.
AB  - Pediculosis capitis is a worldwide infestation caused by Pediculus humanus
      capitis ectoparasite that only lives on the hairs of the scalp. As a result of
      severe itching excoriation, secondary bacterial infection, cervical and occipital
      lymphadenopathy are seen frequently where, sometimes bite reaction, viral
      exanthema mimicking hypersensitivity eruption and conjunctivitis may occur.
      Hereby, with the presentation of a quite rarely seen pediculid case,
      characterized with common autosensitization dermatitis as an -id reaction to
      pediculosis capitis, the importance of exploring the source of the infection
      and/or infestation on the patients who have presented with generalized pruritic
      maculopapular eruption, is emphasized.

PMID- 23169167
TI  - [A case report: elephantiasis].
AB  - Klippel-Trenaunay syndrome (KTS) is a rare disease and a syndrome that is    
      characterized by the triad of congenital port wine stains,venous malformations   
      with or without varicose veins, bone or soft tissue hypertrophy. Lymphatic    
      filariasis is a filarial disease which usually occurs with genital anomalies,    
      pathologies associated with lymphedema or elephantiasis caused by a filarial    
      infectious agent. In this case report, a 20-year-old male patient admitted to    
      our clinic for diagnosis and treatment with right leg edema and lesions    
      compatible with dermatological manifestations. In the list of differential    
      diagnosis, filarial elephantiasis was also thought, consequently KTS was    
      diagnosed. (Turkiye Parazitol Derg 2012; 36: 188-90).

PMID- 23169168
TI  - [A case of persistent urinary schistosomiasis transmitted through Lake Malawi].
AB  - There are only few urinary schistosomiasis cases reported from Turkey. These
      recently diagnosed cases are either associated with overseas journeys or observed
      in foreign citizens visiting our country as afflicted with disease from abroad.
      Our case was infected when working in Africa and was diagnosed with non-Hodgkin's
      lymphoma of the bladder by mistake at the outset. The patient, who had recovered
      after a single-day praziquantel therapy, applied to our clinic due to a relapse
      after 21 months, underwent therapy with praziquantel for the second time. This
      case was presented for discussion with respect to the presence of a chronic
      disease despite therapy and the diagnostic dilemma.

PMID- 23169170
TI  - The US Chlamydia trachomatis control program: successes, shortcomings and ideas
      for the future.

PMID- 23169171
TI  - Implementation and effectiveness of an expedited partner therapy program in an
      urban clinic.
AB  - BACKGROUND: Partner notification of exposure to gonorrhea or chlamydia is
      traditionally conducted by the index case or a disease intervention specialist.
      However, a significant proportion of partners remain untreated and thus are at
      risk for continued transmission. Expedited partner therapy (EPT) obviates the
      requirement for a health care visit by the partner: the index case delivers
      medications to the partner. Although shown to be efficacious in randomized
      control trials, effectiveness studies of delivering EPT in real-world situations
      are needed. We describe the implementation, patient characteristics, and clinical
      impact of an EPT program at the Denver Metro Health Clinic (DMHC). METHODS: We
      identified 2578 patient visits eligible for EPT (heterosexual men or women
      diagnosed as having chlamydia or gonorrhea) from November, 2006, to April, 2011.
      We examined EPT acceptance rates over clinical process improvements. To measure
      clinical impact, we assessed the association between initial acceptance of EPT
      and infection status among 351 patients who returned for retesting. RESULTS:
      Requiring complete documentation of EPT in the clinic electronic medical record
      increased EPT acceptance from 20% to 48%. Expedited partner therapy acceptance
      was associated with a reduced risk of chlamydial reinfection (odds ratio, 0.7;
      95% confidence interval, 0.3-1.6) and a reduced risk of gonorrheal reinfection
      (odds ratio, 0.5; 95% confidence interval, 0.2-1.4); however, these changes were
      not statistically significant. CONCLUSIONS: Expedited partner therapy at the DMHC
      was substantially enhanced by process changes in the clinic and may be associated
      with a decreased risk of reinfection.

PMID- 23169172
TI  - Unprotected sex among HIV-positive treatment-seeking opioid-dependent adults in
      China: a cross-sectional study.
AB  - BACKGROUND: We set out to identify factors associated with unprotected sex among
      HIV-positive patients on methadone maintenance therapy (MMT) in China. METHODS:
      We conducted a cross-sectional study in 60 MMT clinics in Yunnan, Sichuan,
      Guizhou, Guangxi, and Xinjiang provinces, China, with a total of 2742
      participants. RESULTS: The median age of participants was 35 years (range, 19-63
      years), and 78.3% were male. More than half (1471/2742; 53.6%) were married, 6.4%
      (176/2742) had a regular sex partner, and 3.5% (95/2742) had 1 or more occasional
      sex partners. Among married participants, 64.6% (950/1471) had a spouse who was
      HIV negative or of unknown HIV status. Among them, 62.8% (597/950) reported sex
      in the past 30 days, and 31.0% (185/597) reported unprotected sex in the past 30
      days. Multivariate logistic regression identified 3 factors associated with an
      increased risk of unprotected sex: receiving MMT in Guangxi (odds ratio [OR],
      3.72 [2.05-6.75]; P < 0.001) or Xinjiang (OR, 2.23 [1.33-3.73]; P < 0.01), having
      a spouse that is a current or former drug user (OR, 1.80 [1.12-2.90]; P < 0.05),
      and having dropped out of MMT in the past 6 months (OR, 3.05 [1.63-5.71]; P <
      0.001); it also identified 2 factors associated with a decreased risk of
      unprotected sex: being male (OR, 0.46 [0.26-0.79]; P < 0.01) and being aware of
      one's own HIV serostatus (OR, 0.16 [0.10-0.27]; P < 0.001). CONCLUSIONS: Many HIV
      positive opioid-dependent individuals attending MMT continue to engage in high
      risk sexual behaviors. Future efforts should focus on increasing awareness of HIV
      serostatus, retaining patients in MMT, and addressing the specific needs of
      female patients on MMT.

PMID- 23169173
TI  - Put in context: the concurrency intervention simulation study of McCreesh et al.

PMID- 23169174
TI  - Counterbalance of ligand- and self-coupled motions characterizes multispecificity
      of ubiquitin.
AB  - Date hub proteins are a type of proteins that show multispecificity in a time
      dependent manner. To understand dynamic aspects of such multispecificity we
      studied Ubiquitin as a typical example of a date hub protein. Here we analyzed 9
      biologically relevant Ubiquitin-protein (ligand) heterodimer structures by using
      normal mode analysis based on an elastic network model. Our result showed that
      the self-coupled motion of Ubiquitin in the complex, rather than its ligand
      coupled motion, is similar to the motion of Ubiquitin in the unbound condition.
      The ligand-coupled motions are correlated to the conformational change between
      the unbound and bound conditions of Ubiquitin. Moreover, ligand-coupled motions
      favor the formation of the bound states, due to its in-phase movements of the
      contacting atoms at the interface. The self-coupled motions at the interface
      indicated loss of conformational entropy due to binding. Therefore, such motions
      disfavor the formation of the bound state. We observed that the ligand-coupled
      motions are embedded in the motions of unbound Ubiquitin. In conclusion,
      multispecificity of Ubiquitin can be characterized by an intricate balance of the
      ligand- and self-coupled motions, both of which are embedded in the motions of
      the unbound form.

PMID- 23169175
TI  - Prognostic factors in hepatitis C patients with a single small hepatocellular
      carcinoma after radiofrequency ablation.
AB  - BACKGROUND/AIMS: Hepatitis C is a major cause of hepatocellular carcinoma (HCC).
      Radiofrequency ablation (RFA) has been widely performed as a curative treatment
      for small HCC. The knowledge of prognostic factors in hepatitis C patients with
      small HCC after RFA is therefore important. METHODOLOGY: One hundred consecutive
      hepatitis C patients with a single HCC3cm or less treated with RFA were enrolled.
      The cumulative recurrence and survival rates were calculated using Kaplan-Meier
      analysis. Prognostic factors were investigated using the Cox proportional hazard
      mod-el. RESULTS: Five-year local and distant intra hepatic recurrence rates were
      10.4% and 70.9%, respectively. Five-year overall survival and recurrence-free
      survival rates were 60.3% and 15.9%, respectively. Multivarlate analysis revealed
      that an age of 75 years or more[relative hazard (RH) 1.61, p=0.019] and a serum
      al-bumin level less than 3.5g/dL (RH 1.61, p=0.016)were significant factors for
      decreased overall survival. Furthermore, a serum albumin level less than 3.5g/dL
      (RH 1.50, p=0.003) was the only significant factor for decreased recurrence-free
      survival. CONCLUSIONS: This study suggests that host-related factors (age and
      serum albumin level) are important in predicting survival in hepatitis C patients
      with a single small HCC af-ter RFA.

PMID- 23169176
TI  - Liver resection in management of post-cholecystectomy biliary injury: a case
      series.
AB  - BACKGROUND/AIMS: Management of post-cholecystectomy bile duct injuries may, in
      certain cases, require hepatectomy. In the literature, indications for
      hepatectomy in this setting are not clear. METHODOLOGY: A retrospective review of
      our database for patients referred for post-cholecystectomy bile duct injuries
      from January 2003 to January 2008 was performed. RESULTS: We present three cases
      of hepatectomy among 45 patients (6.7%) referred for post-cholecystectomy bile
      duct injuries. Two of these patients had been referred after one or more previous
      attempts at operative repair in an outside hospital. In one patient, the decision
      to perform hepatectomy was based on the proximal pattern of biliary stricture
      aggravated by disruption of the right hepatic artery, leading to irreversible
      secondary sclerosing cholangitis. Biliary stricture also involved bifurcation and
      was complicated by liver atrophy in the 2 other patients. Despite complication(s)
      in 2 out of 3 patients, the long-term outcome was good in all cases. CONCLUSIONS:
      In our experience, the indication for hepatectomy in post-cholecystectomy bile
      duct injuries, combined with vascular injuries and liver atrophy in symptomatic
      patients.

PMID- 23169177
TI  - Choledochoduodenostomy re-evaluated in the endoscopic and laparoscopic era.
AB  - BACKGROUND/AIMS: One of the options for draining an obstructed biliary tree is to
      form a choledochoduodenostomy (CDD). We evaluate our experience with this
      procedure with regard to complications (immediate and late), long term patency
      and patient survival. METHODOLOGY: An analysis was performed on a prospectively
      maintained database of all patients undergoing CDD under a single surgeon from
      1992-2009. Data included pre-operative status, indications for surgery,
      postoperative morbidity and mortality, and complications. RESULTS: Sixty-eight
      CDDs were performed (40 male, 28 female). Thirty-seven (54%) were performed for
      benign disease (group A) and 31 (46%) for malignant disease (histologically
      confirmed, group B). Patients in group B were older (58 years vs. 69 years,
      p=0.009), and had higher preoperative bilirubin (58 vs. 156mg/dL, p=0.0003) and
      alkaline phosphatase (434 vs. 696 U/L, p=0.01). In hospital mortality was 7.5% in
      group A, and 9% in group B. Patients in group A had a shorter postoperative stay
      (p=0.008). Long-term mortality was significantly greater in group B (p<0.0001).
      Long term complications were lower in group A (14%) vs. group B (16%). In group B
      recurrent jaundice occurred in 3 patients (9.7%), of which 2 were successfully
      stented at ERCP, and one patient developed ascending cholangitis. CONCLUSIONS:
      CDD remains a relatively safe and effective surgical option for the treatment of
      obstructive jaundice in both benign and malignant disease. It remains a very
      useful tool where ERCP has failed, in patients with unresectable pancreatic
      malignancies, and in patients with recurrent choledocholithiasis.

PMID- 23169178
TI  - Synergistic effect of IL-1beta and TNF-alpha polymorphisms on the H. pylori
      related gastric pre-malignant condition.
AB  - BACKGROUND/AIMS: We investigated the effect of IL-1beta and TNF-alpha
      polymorphisms, and its synergistic effect with age, gender and H. pylori status
      on the gastric pre-malignant condition. METHODOLOGY: IL-1beta-31(T>C) and 
      511(C>T) and TNF-alpha-857 (C>T) polymorphisms were genotyped in 123 cancer free
      subjects. Degree of histological gastritis in both antrum and corpus, and
      extension of endoscopic gastric atrophy were also evaluated. RESULTS: Significant
      associations were found between degrees of mononuclear cell infiltration
      (p=0.007) and atrophy (p=0.01) in the antrum with IL-1beta-31(T>C) polymorphism,
      and degree of endoscopic gastric atrophy with both IL-1beta-31(T>C), -511(C>T)
      polymorphisms (p=0.03, 0.04, respectively). When subjects were divided into the 3
      groups according to the histological severity of gastric mucosal atrophy: the non
      atrophic gastritis (NA) group (atrophy score=0 and metaplasia score=0), the
      severe atrophic gastritis (SA) group (atrophy score>=2 or metaplasia score>=2),
      and the mild atrophic gastritis (MA) group (all others), synergistic effect was
      found between numbers of IL-1beta-31C, IL-1beta-511T variant alleles with co
      factors on the development of gastric atrophy in the antrum (gender + H. pylori +
      number of IL-1beta-31C allele: p=0.001, age + gender + H. pylori + number of IL
      1beta-31C allele: p=0.0008, gender + H. pylori + number of IL-1beta-511T allele:
      p=0.016, age + gender + H. pylori + number of IL-1beta-511T allele: p=0.013),
      while such association was found for TNF-alpha-857 T allele in the antrum and all
      genotypes in the corpus. CONCLUSIONS: IL-1beta-31C, IL-1beta-511T variant alleles
      may accelerate gastric mucosal inflammation and atrophy, not only by themselves,
      but also through the interaction with co-factors.

PMID- 23169179
TI  - Adjuvant chemotherapy increase survival and decrease recurrence in stage IIA
      colon cancer.
AB  - BACKGROUND/AIMS: The aim of the present study is to evaluate the prognostic
      factors and efficacy of adjuvant chemotherapy in stage IIA colon cancer patients.
      METHODOLOGY: From 1994 to 2004, we retrospectively analyzed 447 patients with
      stage IIA colon cancer. The patients were divided into the surgery only and the
      surgery with adjuvant chemotherapy. The reviewed factors were age, gender, the
      size of tumor, differentiation, the number of harvested lymph nodes,
      lymphovascular invasion, perineural invasion and obstruction. RESULTS: Of the 447
      patients, 351 patients (78.5%) received the adjuvant chemotherapy and 96 patients
      (21.5%) underwent the surgery alone. The significant predictors of survival were
      lymphovascular invasion (p=0.045) and adjuvant chemotherapy (p<0.001) on the
      multivariate analysis. For the recurrence, male (p=0.014), the number of
      harvested lymph node (>=15 vs. <15) (p=0.021), lymphovascular invasion (p=0.050)
      and adjuvant chemotherapy (p=0.049) were significant on the multivariate
      analysis. There were similar therapeutic efficacy for survival and recurrence
      among 5-fluorouracil, capecitabine and uracil/tegafur (p=0.854 and p=0.937,
      respectively). CONCLUSIONS: Lymphovascular invasion and adjuvant chemotherapy
      were independent prognostic factors. Adjuvant chemotherapy was effective in
      preventing recurrence and improving survival for the stage IIA colon cancer
      patients, especially for those patients with less than 15 harvested lymph nodes.

PMID- 23169180
TI  - The efficacy of fondaparinux for the prophylaxis of venous thromboembolism after
      resection for colorectal cancer.
AB  - BACKGROUND/AIMS: The advantages of combined pharmacological and physical methods
      for venous thromboembolism (VTE) prophylaxis after colorectal surgery have not
      been clearly determined. The aim of this study is to compare the efficacy and
      safety of fondaparinux combined with intermittent pneumatic compression (IPC)
      with IPC alone for VTE prophylaxis after resection for colorectal cancer.
      METHODOLOGY: Between June 2008 and March 2010, 137 consecutive patients with
      colorectal cancer (CRC) who underwent colorectal resection in our surgical unit
      were enrolled in the study. Patients were divided into 2 groups. The IPC group
      was treated with IPC alone as controls. The fondaparinux group was treated with
      IPC and received subcutaneous injections of fondaparinux once daily. The aim of
      this study was to compare the efficacy and safety of fondaparinux combined with
      IPC with IPC alone for VTE prophylaxis. RESULTS: The demographic variables and
      risk factors, operating time, blood loss and length of the postoperative hospital
      stay were similar in the two groups. No clinically evident VTE, critical
      bleeding, and postoperative death occurred during the study period. No adverse
      reactions due to fondaparinux were observed. CONCLUSIONS: In patients undergoing
      resection of colorectal cancer, receiving fondaparinux and IPC thromboprophylaxis
      was highly effective, well tolerated and safe. The use of combined modalities for
      VTE prophylaxis is justified in patients at high risk of VTE.

PMID- 23169181
TI  - Suppression of reactive oxygen species develops lymph node metastasis in
      colorectal cancer.
AB  - BACKGROUND/AIMS: Recent evidence indicates that reactive oxygen species (ROS) can
      induce a wide type of cellular responses from proliferation to senescence and
      cell death. ROS may not be an absolute carcinogenic factor or cancer suppressor.
      The aim of this study was to assess the biological paradox of ROS in colorectal
      cancer cells. METHODOLOGY: Blood specimens were obtained from the drainage vein
      of the tumor during operation in 135 patients with colorectal cancer. Serum ROS
      levels were measured using the derivatives of reactive oxygen metabolites (d-ROM)
      test. RESULTS: Serum ROS levels increased significantly in tumor size larger than
      40mm (p<0.01). On the other hand, serum ROS levels decreased significantly in
      patients with lymph node metastasis (p<0.01). Multiple linear regression models
      showed a significant association of serum ROS levels with serum carcinoembryonic
      antigen (CEA) levels (p<0.01) and lymph node metastasis (p=0.026). CONCLUSIONS:
      In colorectal cancer cells, the increase of intracellular ROS is first associated
      with cell growth and invasion. However, a further increase inhibits cancer cell
      proliferation, whereas any decrease in ROS concentration needs to stimulate lymph
      node metastasis. Thus, a precise understanding how ROS are generated and involved
      in lymph node metastasis will help us to design better therapeutic strategies.

PMID- 23169182
TI  - Letter from the editor.

PMID- 23169184
TI  - Professional accountability: implications for primary healthcare nursing
      practice.
AB  - The hallmark of professionalism is accountability, and this is necessary to
      consolidate the professional status of nursing. This article presents a review of
      the concept of professional accountability within the theoretical orientation of
      the role theory. It assumes that the nurse is performing roles that must be duly
      accounted for. It discusses the various areas of professional accountability with
      particular reference to primary healthcare nursing practice. It concludes that
      primary healthcare nurses are involved directly with the public on a daily basis,
      hence the need to be cognizant of their public position, level of responsibility,
      and professional accountability.

PMID- 23169186
TI  - Ethical palliative family nursing care: a new concept of caring for patients and
      families.

PMID- 23169189
TI  - A microfluidic device for studying multiple distinct strains.
AB  - The study of cell responses to environmental changes poses many experimental
      challenges: cells need to be imaged under changing conditions, often in a
      comparative manner. Multiwell plates are routinely used to compare many different
      strains or cell lines, but allow limited control over the environment dynamics.
      Microfluidic devices, on the other hand, allow exquisite dynamic control over the
      surrounding conditions, but it is challenging to image and distinguish more than
      a few strains in them. Here we describe a method to easily and rapidly
      manufacture a microfluidic device capable of applying dynamically changing
      conditions to multiple distinct yeast strains in one channel. The device is
      designed and manufactured by simple means without the need for soft lithography.
      It is composed of a Y-shaped flow channel attached to a second layer harboring
      microwells. The strains are placed in separate microwells, and imaged under the
      exact same dynamic conditions. We demonstrate the use of the device for measuring
      protein localization responses to pulses of nutrient changes in different yeast
      strains.

PMID- 23169191
TI  - Stereoselective synthesis of aminoindanols via an efficient cascade aza-Michael
      aldol reaction.
AB  - An efficient organocatalyzed strategy for the synthesis of 3-amino-1-indanols has
      been developed. This method is complementary to the conventional Friedel-Crafts
      strategy. It is also applicable to the synthesis of enantioenriched 3-amino-1
      indanols.

PMID- 23169192
TI  - It's up to us.

PMID- 23169193
TI  - Telephone screening tests for functionally impaired hearing: current use in seven
      countries and development of a US version.
AB  - BACKGROUND: An estimated 36 million US citizens have impaired hearing, but nearly
      half of them have never had a hearing test. As noted by a recent National
      Institutes of Health/National Institute on Deafness and Other Communication
      Disorders (NIH/NIDCD) Working Group, "In the United States (in contrast to many
      other nations) there are no readily accessible low cost hearing screening
      programs..." (Donahue et al, 2010, p. 2). Since 2004, telephone administered
      screening tests utilizing three-digit sequences presented in noise have been
      developed, validated, and implemented in seven countries. Each of these tests has
      been based on a test protocol conceived by Smits and colleagues in The
      Netherlands. PURPOSE: Investigators from Communication Disorders Technology,
      Inc., Indiana University, and VU University Medical Center of Amsterdam agreed to
      collaborate in the development and validation of a screening test for hearing
      impairment suitable for delivery over the telephone, for use in the United
      States. This test, utilizing spoken three-digit sequences (triplets), was to be
      based on the design of Smits and his colleagues. RESEARCH DESIGN: A version of
      the digits-in-noise test was developed utilizing digit triplets spoken in Middle
      American dialect. The stimuli were individually adjusted to speech-to-noise ratio
      (SNR) values yielding 50% correct identification, on the basis of data collected
      from a group of 10 young adult listeners with normal hearing. A final set of 64
      homogeneous stimuli were selected from an original 160 recorded triplets. Each
      test consisted of a series of 40 triplets drawn at random, presented in a noise
      background. The SNR threshold for 50% correct identification of the triplets was
      determined by a one-down, one-up adaptive procedure. The test was implemented by
      telephone, and administered to listeners with varying levels of hearing
      impairment. The listeners were then evaluated with pure-tone tests and other
      audiometric measures as clinically appropriate. STUDY SAMPLE: Ninety participants
      included 72 who were volunteers from the regular client population at the Indiana
      University Hearing Clinic, and 18 who were recruited with a newspaper ad offering
      a free hearing test. Of the 90 participants, 49 were later determined to have
      mean pure-tone thresholds greater than 20 dB hearing level (HL). DATA COLLECTION
      AND ANALYSIS: The primary data analyses were correlations between telephone test
      thresholds and other measures, including pure-tone thresholds and speech
      recognition tests, collected for the same participants. RESULTS: The correlation
      between the telephone test and pure-tone thresholds (r = 0.74) was within the
      range of correlations observed with successful telephone screening tests in use
      in other countries. Thresholds based on the average of only 21 trials (trials
      five through 25 of the 40-trial tracking history) yielded sensitivity and
      specificity values of 0.80 and 0.83, respectively, using pure-tone average((0.5,
      1.0, 2.0 kHz)) >20 dB HL as the criterion measure. CONCLUSIONS: This US version
      of the digits-in-noise telephone screening test is sufficiently valid to be
      implemented for use by the general public. Its properties are quite similar to
      those telephone screening tests currently in use in most European countries.
      Telephone tests provide efficient, easy to use, and valid screening for
      functional hearing impairment. The results of this test are a reasonable basis
      for advising those who fail to seek a comprehensive hearing evaluation by an
      audiologist.

PMID- 23169194
TI  - Initial-fit approach versus verified prescription: comparing self-perceived
      hearing aid benefit.
AB  - BACKGROUND: Despite evidence suggesting inaccuracy in the default fittings
      provided by hearing aid manufacturers, the use of probe-microphone measures for
      the verification of fitting accuracy is routinely used by fewer than half of
      practicing audiologists. PURPOSE: The present study examined whether self
      perception of hearing aid benefit, as measured through the Abbreviated Profile of
      Hearing Aid Benefit (APHAB; Cox and Alexander, 1995), differed as a function of
      hearing aid fitting method, specifically, manufacturer's initial-fit approach
      versus a verified prescription. The prescriptive fit began at NAL-NL1 targets,
      with adjustments based on participant request. Each of the two fittings included
      probe-microphone measurement. RESEARCH DESIGN: A counterbalanced, cross-over,
      repeated-measures, single-blinded design was utilized to address the research
      objectives. STUDY SAMPLE: Twenty-two experienced hearing aid users from the
      general Bay Pines VA Healthcare System audiology clinic population were
      randomized into one of two intervention groups. INTERVENTION: At the first visit,
      half of the participants were fit with new hearing aids via the manufacturer's
      initial fit while the second half were fit to a verified prescription using probe
      microphone measurement. After a wear period of 4-6 wk, the participants' hearing
      aids were refit via the alternate method and worn for an additional 4-6 wk.
      Participants were blinded to the method of fitting by utilizing probe-microphone
      measures with both approaches. DATA COLLECTION AND ANALYSIS: The APHAB was
      administered at baseline and at the end of each intervention trial. At the end of
      the second trial period, the participants were asked to identify which hearing
      aid fitting was "preferred." The APHAB data were subjected to a general linear
      model repeated-measures analysis of variance. RESULTS: For the three APHAB
      communication subscales (i.e., Ease of Communication, Reverberation, and
      Background Noise) mean scores obtained with the verified prescription were higher
      than those obtained with the initial-fit approach, indicating greater benefit
      with the former. The main effect of hearing aid fitting method was statistically
      significant [F (1, 21) = 4.69, p = 0.042] and accounted for 18% of the variance
      in the data (partial eta squared = 0.183). Although the mean benefit score for
      the APHAB Aversiveness subscale was also better (i.e., lower) for the verified
      prescription than the initial-fit approach, the difference was not statistically
      significant. Of the 22 participants, 7 preferred their hearing aids programmed to
      initial-fit settings and 15 preferred their hearing aids programmed to the
      verified prescription. CONCLUSIONS: The data support the conclusion that hearing
      aids fit to experienced hearing aid wearers using a verified prescription are
      more likely to yield better self-perceived benefit as measured by the APHAB than
      if fit using the manufacturer's initial-fit approach.

PMID- 23169195
TI  - The relationship between high-frequency pure-tone hearing loss, hearing in noise
      test (HINT) thresholds, and the articulation index.
AB  - BACKGROUND: Speech recognition in noise testing has been conducted at least since
      the 1940s (Dickson et al, 1946). The ability to recognize speech in noise is a
      distinct function of the auditory system (Plomp, 1978). According to Kochkin
      (2002), difficulty recognizing speech in noise is the primary complaint of
      hearing aid users. However, speech recognition in noise testing has not found
      widespread use in the field of audiology (Mueller, 2003; Strom, 2003; Tannenbaum
      and Rosenfeld, 1996). The audiogram has been used as the "gold standard" for
      hearing ability. However, the audiogram is a poor indicator of speech recognition
      in noise ability. PURPOSE: This study investigates the relationship between pure
      tone thresholds, the articulation index, and the ability to recognize speech in
      quiet and in noise. RESEARCH DESIGN: Pure-tone thresholds were measured for
      audiometric frequencies 250-6000 Hz. Pure-tone threshold groups were created.
      These included a normal threshold group and slight, mild, severe, and profound
      high-frequency pure-tone threshold groups. Speech recognition thresholds in quiet
      and in noise were obtained using the Hearing in Noise Test (HINT) (Nilsson et al,
      1994; Vermiglio, 2008). The articulation index was determined by using Pavlovic's
      method with pure-tone thresholds (Pavlovic, 1989, 1991). STUDY SAMPLE: Two
      hundred seventy-eight participants were tested. All participants were native
      speakers of American English. Sixty-three of the original participants were
      removed in order to create groups of participants with normal low-frequency pure
      tone thresholds and relatively symmetrical high-frequency pure-tone threshold
      groups. The final set of 215 participants had a mean age of 33 yr with a range of
      17-59 yr. DATA COLLECTION AND ANALYSIS: Pure-tone threshold data were collected
      using the Hughson-Weslake procedure. Speech recognition data were collected using
      a Windows-based HINT software system. Statistical analyses were conducted using
      descriptive, correlational, and multivariate analysis of covariance (MANCOVA)
      statistics. RESULTS: The MANCOVA analysis (where the effect of age was
      statistically removed) indicated that there were no significant differences in
      HINT performances between groups of participants with normal audiograms and those
      groups with slight, mild, moderate, or severe high-frequency hearing losses. With
      all of the data combined across groups, correlational analyses revealed
      significant correlations between pure-tone averages and speech recognition in
      quiet performance. Nonsignificant or significant but weak correlations were found
      between pure-tone averages and HINT thresholds. CONCLUSIONS: The ability to
      recognize speech in steady-state noise cannot be predicted from the audiogram. A
      new classification scheme of hearing impairment based on the audiogram and the
      speech reception in noise thresholds, as measured with the HINT, may be useful
      for the characterization of the hearing ability in the global sense. This
      classification scheme is consistent with Plomp's two aspects of hearing ability
      (Plomp, 1978).

PMID- 23169196
TI  - Subjective and objective outcomes from new BiCROS technology in a veteran sample.
AB  - BACKGROUND: Patients with single-sided deafness (SSD), where one ear has an
      unaidable hearing loss and the other ear has normal or aidable hearing, often
      complain of difficulties understanding speech and localizing sound sources, and
      report a higher self-perceived hearing disability. Patients with SSD may benefit
      from using contralateral routing of signal (CROS) or bilateral contralateral
      routing of the signal (BiCROS) amplification. Dissatisfaction of previously
      available (Bi)CROS devices has been reported, such as, interfering transmissions,
      low-fidelity sound quality, poor "user-friendly" set-up, and a bulky and
      cosmetically cumbersome appearance. PURPOSE: Recent advances in hearing aid
      technology have improved (Bi)CROS hearing aids; however, these devices have not
      been experimentally evaluated. We hypothesized that newer technology with reports
      of improved digital signal processing, wireless transmission, and physical design
      would be as good, or better than, our participants' previous-generation BiCROS
      systems. RESEARCH DESIGN: A within-subjects, pretest-posttest design was
      executed. STUDY SAMPLE: Thirty-nine veterans (one female, 38 males; mean age = 74
      yr, range = 49-85 yr) from the Audiology Section of the Bay Pines Veterans Affair
      Healthcare System participated. All participants were previously experienced
      BiCROS hearing aid users with varying degrees of sensorinerual hearing impairment
      in their better ear. INTERVENTION: Participants were provided at least 4 wk of
      consistent use with the new BiCROS. DATA COLLECTION AND ANALYSES: Participants
      completed three research visits. At Visit 1, with their previous BiCROS, and at
      Visit 3, with their new BiCROS, the following objective and subjective measures
      were obtained: (1) soundfield speech-in-noise testing using the Words-In-Noise
      (WIN) test; (2) speech, spatial, and qualities of the hearing scale (SSQ)
      questionnaire; (3) selected questions from the MarkeTrak questionnaire; and, (4)
      three open-ended questions. Data were analyzed using parametric and nonparametric
      statistics. RESULTS: Overall, the objective (WIN) and subjective (SSQ, MarkeTrak,
      and open-ended questions) measures indicated that the new BiCROS provided better
      outcomes than the previous BiCROS system. In addition, an overlap of favorable
      results was seen across measures. CONCLUSIONS: Of the 39 participants, 95%
      reported improvements with the new BiCROS and chose to utilize the device
      regularly. The favorable objective and subjective outcomes indicate that the new
      BiCROS system is as good, or better than, what was previously utilized by our
      sample of veterans.

PMID- 23169197
TI  - The Hearing Impairment Impact-Significant Other Profile (HII-SOP): a tool to
      measure hearing loss-related quality of life in spouses of people with hearing
      loss.
AB  - BACKGROUND: Third-party hearing loss-related quality of life (HLQoL) reports
      measure the third-party disability as a result of communicating regularly with
      someone with hearing loss. Scales with known psychometric characteristics
      validated on a diverse subject population are needed in order to describe the
      activity limitations and participation restrictions experienced by spouses as a
      result of living with an individual with hearing loss. PURPOSE: The purpose of
      the present study was to develop a scale to measure third-party HLQoL in spouses
      of people with hearing loss with acceptable psychometric characteristics. This
      scale is known as the Hearing Impairment Impact-Significant Other Profile (HII
      SOP). RESEARCH DESIGN: In Study 1, the initial test items were developed and
      evaluated with a factor analysis for adequate construct validity. In Study 2, the
      internal consistency reliability, the validity, and the test-retest reliability
      of the revised test were evaluated. STUDY SAMPLE: In Study 1, 120 people between
      34 and 87 yr of age participated and in Study 2, 164 people between 23 and 88 yr
      of age participated. DATA COLLECTION AND ANALYSIS: In Study 1, a 41-item
      questionnaire was developed based on five content areas: physical adjustment,
      social activities, emotional reaction, intimate relationship, and change in
      roles. The scale was submitted to a factor analysis to analyze interrelationships
      among items, determine the underlying dimensions, and select items for the final
      scale. In Study 2, the internal consistency reliability, construct validity, and
      test-retest reliability were evaluated in the revised 20-item questionnaire. The
      internal-consistency reliability was measured using Cronbach's alpha. Validity
      was assessed by observing the correlations of the new scale with well-established
      scales measuring related constructs: overall health-related quality of life,
      marital communication, HLQoL, and negative affect, in both the person with
      hearing loss and the spouse. Test-retest reliability was measured in a subset of
      the spouses who completed the HII-SOP between 2 and 4 wk after the initial scale
      was completed. RESULTS: The HII-SOP is a 20-item scale with three subscales which
      measure: (1) the emotions that arise when having a spouse with hearing loss as
      well as the impact of the hearing loss on the marital relationship, (2) the
      impact of the hearing loss on the social life of the spouse, and (3) the
      communication strategies used by the spouse. The scale and its subscales have
      adequate internal-consistency reliability suggesting that the 20 items do measure
      a single construct and the subscales do measure distinct subconstructs. The HII
      SOP scale was significantly correlated with measures expected to relate to the
      construct of third-party disability associated with hearing loss. Finally, the
      HII-SOP scale has adequate test-retest reliability (r = 0.90) and the 95%
      critical differences is 19.7 points. CONCLUSIONS: The HII-SOP is a scale to
      measure third-party HLQoL in spouses of individuals with hearing loss. Scores of
      20-39 reflect mild third-party disability, scores of 40-59 reflect moderate third
      party disability, and scores >60 reflect severe third-party disability associated
      with hearing loss.

PMID- 23169198
TI  - Hearing loss associated with xylene exposure in a laboratory worker.
AB  - BACKGROUND: Xylene is an organic solvent, widely used in histology laboratories
      and other occupational settings. Research in animals has demonstrated that xylene
      induces outer hair cell damage. Evidence regarding the effects of xylene in
      humans is only available from studies investigating workers exposed to mixtures
      of solvents containing xylene. These data indicate that mixtures of solvents
      containing xylene may induce hearing loss and central auditory dysfunction.
      PURPOSE: To comprehensively evaluate the peripheral and central auditory system
      of a histology laboratory worker exposed to xylene, who had presented with
      bilateral mild sensorineural hearing loss at an initial assessment. RESEARCH
      DESIGN: A case report of a male histology laboratory worker who has been exposed
      to xylene for over 20 yr. RESULTS: A diagnosis of bilateral mild sensorineural
      hearing loss of cochlear origin was made on the basis of otological,
      neuroimaging, and audiological examinations. Results indicating the absence of
      transient-evoked otoacoustic emissions, and auditory brainstem responses as
      expected for a mild cochlear hearing loss, were obtained. CONCLUSIONS: The
      observed bilateral mild sensorineural hearing loss was considered to have been
      induced by xylene exposure, due to the absence of any other etiological factors
      related to the onset of hearing loss. The results found in this patient are in
      agreement with animal data indicating xylene-induced ototoxicity. Xylene-exposed
      individuals should be audiologically monitored on a regular basis.

PMID- 23169200
TI  - Retraction.

PMID- 23169199
TI  - Retraction.

PMID- 23169203
TI  - Procedure for quantitative (1)H magnetic resonance spectroscopy and tissue
      characterization of human brain tissue based on the use of quantitative magnetic
      resonance imaging.
AB  - PURPOSE: Existing methods for quantitative magnetic resonance spectroscopy are
      not widely used for magnetic resonance spectroscopy examinations in clinical
      practice due to the lengthy and difficult workflow. In this report, we aimed to
      investigate whether metabolite concentrations show co-variation with relaxation
      parameters (R1,H2O,R2,H2O), water concentration (CH2O), and age, using a
      quantitative magnetic resonance spectroscopy method, which is suitable for a
      clinical setting. METHODS: We performed 166 single voxel magnetic resonance
      spectroscopy measurements in the white matter and thalamus in 47 healthy
      subjects, aged 18-72 years. Whole brain R1,H2O, R2,H2O, and CH2O maps were
      determined for each subject using quantitative magnetic resonance imaging.
      Absolute metabolite concentrations were calculated by calibrating the water
      scaled magnetic resonance spectroscopy, using the quantitative magnetic resonance
      imaging maps of R1,H2O, R2,H2O, and CH2O. RESULTS: Absolute concentrations in
      white matter of total Creatine and myo-Inositol were correlated with age (total
      Creatine: 12 +/- 4 MUM/year, P < 0.01; myo-Inositol: 23 +/- 9 MUM/year, P <
      0.05), suggesting a process of increased glia density in aging white matter.
      Moreover, total Creatine and total N-acetylaspartate were inversely correlated
      with the R1,H2O and positively correlated with the CH2O of white matter. In
      addition, the Cramer-Rao lower bound was biased regarding the metabolite
      concentration, suggesting that should not be used as a quality assessment.
      CONCLUSION: The implemented method was fast, robust, and user-independent.

PMID- 23169204
TI  - Neuromuscular properties of the thigh muscles in patients with Ehlers-Danlos
      syndrome.
AB  - INTRODUCTION: Ehlers-Danlos syndrome (EDS), a connective tissue disorder, may
      lead to impaired contractile function of lower limb muscles. METHODS: To test
      this hypothesis and to understand the possible mechanisms involved, isometric
      function of the thigh muscles was investigated at different joint angles (30
      degrees , 60 degrees , and 90 degrees  of knee flexion) in 7 tenascin-X (TNX)
      deficient EDS patients. RESULTS: There was reduced maximal voluntary torque of
      the knee extensors (but not knee flexors) across all joint angles in the
      patients. Time to reach maximal rate of torque development was delayed, and
      voluntary activation capacity was reduced in patients compared with controls,
      particularly at 30 degrees . CONCLUSIONS: EDS is associated with muscle weakness,
      most likely due to increased compliance of the series-elastic component of muscle
      tissue and failure of maximal voluntary muscle activation. Further research is
      required to understand the influence of reduced voluntary activation on the
      severe fatigue reported by EDS patients.

PMID- 23169206
TI  - Food avoidance diets for systemic, lip, and oral contact allergy:  an american
      contact alternatives group article.
AB  - BACKGROUND: Patients with systemic, lip, and oral contact allergy will often
      improve with an elimination diet of related ingredients. Elimination diets for
      avoidance of many common preservatives, antioxidants, and other food additives
      have not been published. OBJECTIVE: This study aims to create rational
      elimination diets (including lists of acceptable alternative foods) for several
      common food ingredients (propylene glycol, sorbic acid/sorbates, aspartame,
      benzoic acid/benzoates, propionic acid and propionates, gallates, and benzoyl
      peroxide). METHODS: Data from www.foodfacts.com, a Web site listing ingredient
      information for more than 75,000 foods, were extracted and sorted into products
      types, and an elimination diet was created for each of these food-related
      substances. Easily obtainable alternatives were identified and listed.
      CONCLUSIONS: Use of food elimination diets may yield improvement in some patients
      who have not improved with external avoidance of allergens.

PMID- 23169207
TI  - Occupational contact dermatitis in hairdressers/cosmetologists:  retrospective
      analysis of north american contact dermatitis group data, 1994 to 2010.
AB  - BACKGROUND: European studies document that occupational contact dermatitis (CD)
      is common in hairdressers, but studies from North America are lacking.
      OBJECTIVES: The objectives of this study were to estimate the prevalence of
      occupational CD among North American hairdressers/cosmetologists (HD/CS) and to
      characterize responsible allergens and irritants as well as their sources.
      METHODS: A cross-sectional analysis of patients patch tested by the North
      American Contact Dermatitis Group between 1994 and 2010 was conducted. RESULTS:
      Of 35,842 patients, 432 (1.2%) were HD/CS. Significantly, most of the HD/CS were
      female (89.8%) and younger than 40 years (55.6%) as compared with non
      hairdressers (P < 0.0001). The rates for allergic and irritant CD in HD/CS were
      72.7% and 37.0%, respectively. The most common body site of involvement was the
      hand, and this was significantly more common than in non-HD/CS (P < 0.0001). The
      most frequent currently relevant and occupationally related allergens were
      glyceryl thioglycolate, p-phenylenediamine, nickel sulfate, 2-hydroxyethyl
      methacrylate, and quaternium-15. Hair dyes, permanent wave solutions, and other
      hair products were common sources of allergens. The North American Contact
      Dermatitis Group allergen series missed at least 1 occupationally-related
      allergen in 26.2% of patients. CONCLUSIONS: Contact dermatitis in North American
      HD/CS is common, and occupationally related allergens are those found in HD/CS
      products. Supplemental hairdressing/cosmetology antigen series are important in
      detecting all occupationally related allergens in this population.

PMID- 23169208
TI  - Patch testing with textile allergens:  the mayo clinic experience.
AB  - BACKGROUND: Recognition of allergic contact dermatitis attributed to textile dyes
      and resins is steadily increasing. OBJECTIVE: This study aims to review the
      results of patch testing with a textile series at our institution and to compare
      with previously published reports. METHODS: We performed a retrospective review
      of results in patients who underwent patch testing using a series of textile dyes
      and resins from January 1, 2000, through September 30, 2011. RESULTS: A total of
      671 patients (mean age, 56.5 years; female, 65.9%) were patch tested with the
      textile series (42 dyes and resins). These patients were also generally tested
      with the standard patch test series (n = 620). Of the patients, 219 (32.6%)
      demonstrated allergic reaction to 1 or more textile dyes and resins, and 71
      (10.6%) manifested irritant reactions. The most frequent allergens were disperse
      blue 106 1% (8.3%), disperse blue 124 1% (8.0%), and melamine formaldehyde 7%
      (8.0%). Of patients tested with the standard series, 36 (5.8%) showed a positive
      reaction to the traditional textile screening allergen p-phenylenediamine 1%.
      CONCLUSIONS: Supplementing the standard series with the textile series increased
      detection of textile allergies. In patients suspected of textile allergy,
      addition of the textile series is necessary for appropriate diagnosis.

PMID- 23169209
TI  - Allergic contact dermatitis in children with and without atopic dermatitis.
AB  - BACKGROUND: Prevalence and causes of allergic contact dermatitis (ACD) in
      children vary with time and geographical area. OBJECTIVE: This study aimed to
      determine the relevant allergens causing ACD in children and the relation between
      ACD and atopic dermatitis (AD). METHODS: A cohort study on 349 children (0-15
      years old) patch tested over a 7-year period was conducted. RESULTS: Patch test
      results were positive for at least 1 allergen in 69.3% of patients and were
      relevant in 69.8%. The highest sensitization rate (76.7%) was observed in
      children who are 0 to 5 years old (n = 86, 64% females), followed by the group of
      6- to 10-year olds (70%, n = 157, 47.8% females), whereas 62.3% of 11- to 15-year
      old children (n = 106, 59.4%) were sensitized. The most frequent allergens were
      nickel (16.3%), cobalt (6.9%), Kathon CG (5.4%), potassium dichromate (5.1%),
      fragrance mix (4.3%), and neomycin (4.3%). Body areas mostly affected were upper
      limbs and hands (31%). Approximately one third of children also had AD. Allergic
      contact dermatitis was more widespread in children with AD. Patch tests resulted
      positive in 55.3% (50% relevant) of AD compared with 76.9% (77.5% relevant) of
      the children without AD. Sensitizers were similar to children without AD.
      CONCLUSIONS: Very young children showed a high rate of relevant positive patch
      test reactions to common haptens. Allergic contact dermatitis may easily coexist
      with AD.

PMID- 23169210
TI  - Bloodroot.
AB  - BLOODROOT (Sanguinaria canadensis) is a flowering herb that can be used as a
      drug. Historically, it was widely used by Native Americans in blood tonification
      and purification, pain and fever relief, and wound healing. Bloodroot plants have
      been advertised to impart a wide range of medical properties, and many bloodrood
      containing products are commercially available. Potential side effects of
      bloodroot products include significant tissue destruction, escarification, and
      keloid formation. Therefore, it is critical for clinicians to be aware of
      potential risks, educate their patients on treatment options, and be able to
      recognize the cutaneous effects of bloodroot and other escharotic agents.

PMID- 23169211
TI  - Occupational eczema and asthma in a hairdresser caused by hair-bleaching
      products.
AB  - Occupational allergic contact eczema and asthma caused by bleaching agents is
      seen in hairdressers. Bleaching agents contain persulfate salts, which are known
      to induce immediate reactions such as rhinitis, asthma, contact urticaria, and
      anaphylaxis. The immunologic mechanism is not, however, fully understood. The
      specific inhalation challenge test is considered to be the gold standard for
      diagnosing occupational asthma and rhinitis. However, this test is not always
      accessible. Therefore, the diagnosis of occupational allergic asthma caused by
      persulfate salts is made by combining a clinical history, a diagnosis of asthma,
      and a positive skin prick test (SPT). Standardized methods for performing SPT
      with persulfate salts are warranted. A case of a young hairdresser with
      occupational asthma and hand eczema caused by persulfate salts is presented, and
      the procedure for performing the SPT with ammonium persulfate and potassium
      persulfate is described in detail.

PMID- 23169212
TI  - Immediate and delayed hypersensitivity to systemic corticosteroids:  2 case
      reports.
AB  - BACKGROUND: Both immediate, type I reactions and delayed hypersensitivity, type
      IV reactions to systemic corticosteroid preparations have been reported. Type I
      reactions are rare, with delayed hypersensitivity reactions being slightly more
      common. CASES: A 33-year-old woman presented repeatedly to the emergency
      department with asthma attacks. She developed pruritus and hives approximately 30
      minutes after the administration of parenteral corticosteroids. Her respiratory
      status deteriorated approximately 6 hours after she received the corticosteroids.
      An acute eczematous dermatitis on her face, neck, and upper body appeared 24
      hours after administration of the corticosteroids. The dermatitis peaked at 72
      hours. Intradermal testing to Solu-Medrol, Solu-Cortef, prednisone, and Decadron
      confirmed a type I, anaphylactoid reaction. The dermatitis that presented 24
      hours after administration of the parenteral corticosteroids is consistent
      clinically with a type IV delayed hypersensitivity reaction to the
      corticosteroids. A second patient, a 51-year-old woman, developed urticarial
      lesions that lasted approximately 30 minutes, immediately after intralesional
      triamcinolone injections for keloid scars. Intradermal testing was performed. She
      showed a positive reaction to triamcinolone confirming a type I allergy to this
      steroid. CONCLUSIONS: It is important to consider an allergy to corticosteroids
      in patients with worsening anaphylactic symptoms after administration of systemic
      corticosteroids.

PMID- 23169213
TI  - Ethylhexylglycerin-a contact allergen in cosmetic products.

PMID- 23169214
TI  - A linear allergic contact dermatitis to p-tert-butylphenol formaldehyde resin
      sectorially present in a neoprene orthopedic brace: role of spectroscopy.

PMID- 23169215
TI  - Severe marking-nut dermatitis.

PMID- 23169217
TI  - Comparison of allergEAZE allergens to Chemotechnique Diagnostics allergens in the
      evaluation of contact allergy.

PMID- 23169216
TI  - A case of photoallergic contact dermatitis caused by unusual exposure to
      ketoprofen.

PMID- 23169218
TI  - Allergic contact dermatitis with contact urticaria to colophony from an
      alternative remedy.

PMID- 23169219
TI  - Occupational airborne allergic contact dermatitis to olanzapine.

PMID- 23169220
TI  - Effects of immunomodulatory agents on patch testing:  expert opinion 2012.

PMID- 23169221
TI  - Nanoscale inhomogeneities in thermoresponsive polymers.
AB  - This article highlights the occurrence and nature of nanoscale inhomogeneities in
      thermoresponsive polymers and focuses on different experimental techniques for
      their observation and characterization. Such inhomogeneities can be regarded as
      nanoscopic domains of collapsed polymer segments (or of a small number of
      unimers), which provide a nonpolar, hydrophobic interior. Continuous wave (CW)
      electron paramagnetic resonance (EPR) spectroscopy on amphiphilic reporter
      molecules (spin probes) as an intrinsically local technique is particularly
      emphasized. In combination with different ensemble-averaging methods, it provides
      a holistic understanding of the often inhomogeneous nanoscale processes during
      the temperature-induced collapse of a thermoresponsive polymer.

PMID- 23169222
TI  - Tobacco smoking and solid organ transplantation.
AB  - Smoking, both by donors and by recipients, has a major impact on outcomes after
      organ transplantation. Recipients of smokers' organs are at greater risk of death
      (lungs hazard ratio [HR], 1.36; heart HR, 1.8; and liver HR, 1.25), extended
      intensive care stays, and greater need for ventilation. Kidney function is
      significantly worse at 1 year after transplantation in recipients of grafts from
      smokers compared with nonsmokers. Clinicians must balance the use of such higher
      risk organs with the consequences on waiting list mortality if the donor pool is
      reduced further by exclusion of such donors. Smoking by kidney transplant
      recipients significantly increases the risk of cardiovascular events (29.2% vs.
      15.4%), renal fibrosis, rejection, and malignancy (HR, 2.56). Furthermore, liver
      recipients who smoke have higher rates of hepatic artery thrombosis, biliary
      complications, and malignancy (13% vs. 2%). Heart recipients with a smoking
      history have increased risk of developing coronary atherosclerosis (21.2% vs.
      12.3%), graft dysfunction, and loss after transplantation. Self-reporting of
      smoking is commonplace but unreliable, which limits its use as a tool for
      selection of transplant candidates. Despite effective counseling and
      pharmacotherapy, recidivism rates after transplantation remain high (10-40%).
      Transplant services need to be more proactive in educating and implementing
      effective smoking cessation strategies to reduce rates of recidivism and the
      posttransplantation complications associated with smoking. The adverse impact of
      smoking by the recipient supports the requirement for a 6-month period of
      abstinence in lung recipients and cessation before other solid organs.

PMID- 23169223
TI  - Roles of Toll-like receptors in allogeneic islet transplantation.
AB  - BACKGROUND: Toll-like receptors (TLRs) are involved in the rejection of solid
      organ allografts. However, the roles of TLRs in islets are still controversial.
      We investigated the roles of TLRs in donor islets together with those in
      recipients in allogeneic islet transplantation. METHODS: To assess the roles of
      TLRs in either donor islets or recipients, allogeneic islet transplantation was
      performed using myeloid differentiation factor 88 (MyD88)-knockout (KO), TLR4-KO,
      or Toll/interleukin-1 receptor domain-containing adaptor-inducing interferon-beta
      (TRIF)-KO mice. RESULTS: Both polyriboinosinic polyribocytidylic acid and
      lipopolysaccharide (LPS) stimulation induced the mRNA expression of regulated and
      normal T cell expressed and secreted, interferon-gamma-inducible protein-10,
      monocyte chemotactic protein-1, interleukin-8, and inducible nitric oxide
      synthase in murine islets, whereas the induction was attenuated in TRIF-KO,
      interferon-beta promoter stimulator-1-KO, and TLR4-KO mice. When islets from
      MyD88-KO, TLR4-KO, or TRIF-KO C57BL/6 mice were transplanted to BALB/c
      recipients, graft survival was not better than that of wild-type (WT) islets.
      However, the survival of the MyD88-KO islet allograft was significantly prolonged
      when combined with anti-CD40L. In parallel, LPS stimulation in donor islets
      interfered with anti-CD40L blockade-mediated long-term survival of islet
      allografts in TLR4-KO recipients. LPS stimulation increased the perigraft
      infiltration of both T cells and macrophages. Then again, when islets from WT
      BALB/c mice were transplanted to MyD88-KO, TRIF-KO, or WT C57BL/6 mice, there was
      no difference in graft survival, although some of the MyD88-KO recipients
      obtained long-term graft survival. However, anti-CD40L prolonged graft survival
      significantly in MyD88-KO recipients. The absence of MyD88 in either donors or
      recipients decreased the perigraft infiltration of inflammatory cells when
      combined with anti-CD40L. CONCLUSIONS: TLRs in both donor islets and recipients
      are involved in islet allograft rejection.

PMID- 23169224
TI  - High frequency of rejections in HIV-positive recipients of kidney
      transplantation: a single center prospective trial.
AB  - BACKGROUND: This is a single institution report of the incidence of combined
      acute antibody-mediated rejection (ABMR) + acute cellular rejection (ACR) [mixed
      rejection] in HIV (+) kidney transplant recipients. METHODS: We prospectively
      enrolled 92 HIV (+) patients who received a kidney transplant between 2001 and
      2009. There were three cohorts: no rejection [n=26], ACR [n=53], and mixed
      rejections (ABMR and ACR) [n=13]. Immunosuppression comprised of basiliximab,
      cyclosporine, sirolimus, and steroid minimization. Fisher exact tests for
      categorical variables, t test for continuous variables, and Kaplan-Meier
      estimates were used to describe events. RESULTS: Mixed rejections were seen in
      all 13 HIV (+) kidney transplant recipients (14%) with a median time to ABMR of
      48 days. Acute cellular rejection occurred in 28% at 1 month and 55% at 12
      months. eGFR was lower for recipients who experienced ABMR versus those
      experiencing ACR and those never experiencing rejection up to 3 years (14 +/- 9.4
      vs 19 +/- 3.3 vs 29 +/- 7.3 mL/min, respectively). Kaplan-Meier showed that graft
      survival up to 9 years was worse in recipients experiencing mixed rejection.
      Suboptimal donors with terminal creatinine greater than 2.5 mg/dL was associated
      with increased incidence of mixed rejections versus cellular rejections and no
      rejection (42% vs 17% vs. 8%, respectively). CONCLUSIONS: Our single center study
      showed a relatively higher incidence of mixed rejection compared with that
      reported for non-HIV transplant recipients. A donor terminal serum creatinine
      greater than 2.5 mg/dL predicted mixed rejection, which was associated with poor
      outcomes. Donor selection and optimization of immunosuppression may be critical
      in these patients.

PMID- 23169225
TI  - A report of 15 hand allotransplantations in 12 patients and their outcomes in
      China.
AB  - BACKGROUND: Limb allotransplantation is emerging as a promising solution to the
      loss of a limb with the development of advanced surgical techniques and new,
      highly effective immunosuppressive agents. METHODS: We retrospectively reviewed
      the records of 15 hand allotransplantations in 12 patients in China which were
      performed from September 1999 to May 2008. RESULTS: In total, there were 1
      bilateral and 5 unilateral hand transplantations, 3 unilateral and 2 bilateral
      forearm transplantations, and 1 palm and 1 thumb transplantation. The average age
      of recipients was 34 +/- 11.3 years (range, 19-52 years). At 1-year follow-up,
      all grafts were viable and with good function. Of the 15 hands transplanted, 8
      are currently viable (mean follow-up, 52 +/- 36.3 months; range, 16-112 months),
      including all 3 bilateral cases. Reasons for graft failure were rejection and
      failure of compliance with immunosuppressive therapy. CONCLUSIONS: Long-term
      survival of hand transplantation with appropriate immunosuppression is feasible,
      and satisfactory functional results have been achieved. Careful pretransplant
      psychologic and social evaluation, consideration of the financial burden of long
      term immunosuppressive medications, and close multispecialty collaboration is
      critical for good outcomes. Limb rejection was related with immunosuppression
      use. Further study and experience is required before hand allotransplantation can
      become a generally recommended treatment.

PMID- 23169226
TI  - [Presentation].

PMID- 23169227
TI  - [Proposed alternative to standard apomorphine challenge test].
AB  - Subcutaneous apomorphine injection is used as a rescue treatment in the off
      periods in moderate and advanced Parkinson's disease and also when required to
      assess the dopaminergic response. It is not recommended as a diagnostic tool in
      Parkinson's disease because it has more side effects and is less specific than
      chronic response to levodopa. To calculate the dosage, an apomorphine challenge
      test is performed, generally taking quite time and testing several doses. We
      propose an alternative apomorphine challenge test, with a single injection and a
      higher initial dosage of 2-4 mg, as well as to schedule treatment according to
      the obtained response at that dosage. This procedure saves time and also allows a
      better planning of medical attention.

PMID- 23169228
TI  - [Candidate patient for treatment with continuous apomorphine infusion].
AB  - Subcutaneous apomorphine infusion has been shown to be effective in reducing
      motor fluctuations and, to a lesser extent, also the levodopa induced dyskinesias
      in patients with advanced Parkinson's disease (PD). Based on the literature data,
      the following article reviews the clinical features of PD patients in order to be
      considered candidates for this therapy. In general, the vast majority of patients
      with advanced PD can benefit from this therapy and the authors' experience
      suggests that it should be considered as soon as the conventional pharmacological
      therapy fails to significantly reduce the number of daily off hours.

PMID- 23169229
TI  - [Subcutaneous continuous apomorphine infusion: treatment initiation and follow
      up].
AB  - Continuous apomorphine infusion has been an established treatment for advanced
      Parkinson's disease for over two decades. This article reviews the different
      methods for starting treatment and propose a consensus methodology for it, as
      well as for the modification of prior treatment, in order to standardize and
      reduce the variability of clinical practice.

PMID- 23169230
TI  - [Treatment of apomorphine infusion adverse effects: subcutaneous nodules and
      neuropsychiatric complications].
AB  - Subcutaneous nodules and neuropsychiatric complications are the most relevant
      adverse effects during apomorphine infusion treatment. Subcutaneous nodules
      appear in almost all the patients and accurate information and training of both
      patient and caregiver is essential to minimise their impact on the treatment.
      Although neuropsychiatric complications are not more frequent than with other
      dopaminergic treatments, they are linked with increasing difficulty of treatment
      and worsening of patient's quality of life.

PMID- 23169231
TI  - [Limits of conventional oral and transdermal medication in Parkinson's disease].
AB  - At the present time, we have effective and potent antiparkinsonian drugs
      available which allow patients to have an acceptable functional capacity during
      the early years of Parkinson's disease. Yet, as time goes by, motor and
      functional deterioration develop, partly due to the presence of motor and non
      motor complications. The conventional medication is unable to provide an adequate
      response if the motor fluctuations are beyond 3-4 hours of duration. At this
      point, it is reasonable to consider other therapies; among them subcutaneous
      apomorphine injection must be taken into account due to its simplicity and
      efficacy and later on, subcutaneous apomorphine infusion. Apomorphine is a very
      effective and clearly underused drug in the treatment of advanced Parkinson's
      disease.

PMID- 23169232
TI  - [Candidate patient for subcutaneous apomorphine injection].
AB  - Subcutaneous apomorphine injection is a fast-action, effective treatment option,
      that enables many patients to be rescued from predictable and non-predictable off
      episodes. It is an easy-to-use technique after minimum training. The neurologist
      can use it on patients with advanced Parkinson's disease only by following some
      basic procedures which are easily implemented in outpatient setting.

PMID- 23169233
TI  - HIPK2: A tumour suppressor that controls DNA damage-induced cell fate and
      cytokinesis.
AB  - In response to DNA-damage, cells have to decide between different cell fate
      programmes. Activation of the tumour suppressor HIPK2 specifies the DNA damage
      response (DDR) and tips the cell fate balance towards an apoptotic response.
      HIPK2 is activated by the checkpoint kinase ATM, and triggers apoptosis through
      regulatory phosphorylation of a set of cellular key molecules including the
      tumour suppressor p53 and the anti-apoptotic corepressor CtBP. Recent work has
      identified HIPK2 as a regulator of the ultimate step in cytokinesis: the
      abscission of the mother and daughter cells. Since proper cytokinesis is
      essential for genome stability and maintenance of correct ploidy, this finding
      sheds new light on the tumour suppressor function of HIPK2. Here we highlight the
      molecular mechanisms coordinating HIPK2 function and discuss its emerging role as
      a tumour suppressor.

PMID- 23169234
TI  - A new approach to improve the specificity of flow-mediated dilation for
      indicating endothelial function in cardiovascular research.
AB  - Flow-mediated dilation (FMD) is a noninvasive indicator of endothelial function
      and is routinely expressed as the percentage change in arterial diameter (FMD%)
      from a resting baseline (Dbase) to a postischemic peak (Dpeak). This expression
      is equivalent to the ratio of Dpeak/Dbase and is, therefore, dependent on
      important statistical assumptions, which have never been analysed in the context
      of FMD%. We aimed to investigate these assumptions, via a comparison of FMD
      between samples of children and adults, as well as to explore other approaches to
      scaling diameter change for Dbase. We found that FMD% did not scale accurately
      for interindividual differences in Dbase but, as expected, overestimated
      endothelial function for low Dbase and vice versa. We argue that this imprecise
      scaling of FMD% is predictable, not explained by physiology and is probably
      common. This problem is resolved by applying scaling principles, whereby the
      difference in diameter is the outcome and Dbase is a covariate in a logarithmic
      linked generalized linear model. A specific allometric expression of FMD can be
      derived and we found this to be Dpeak/Dbase rather than a simple ratio in our
      particular dataset. We found that sample differences in endothelial function were
      inaccurate with FMD% versus our new allometric approach, and that FMD%
      misclassified participants into 'high' and 'low'cohorts, which has implications
      for prognostic-type studies. We conclude that the general use of FMD% could have
      led to biased comparisons of different conditions and/or populations in past
      studies. Our new approach to scaling FMD is flexible for different datasets and
      is not based on the current assumption that a percentage change is appropriate in
      all circumstances.

PMID- 23169235
TI  - Obesity markedly attenuates the validity and performance of all
      electrocardiographic criteria for left ventricular hypertrophy detection in a
      group of black African ancestry.
AB  - AIM: To assess the impact of obesity on the validity and performance of
      electrocardiographic criteria for the detection of left ventricular hypertrophy
      (LVH) in a group of participants of black African ancestry with a high prevalence
      of obesity. METHODS: Electrocardiographic voltage criteria for the detection of
      echocardiographic LVH [left ventricular mass index (LVMI) >51 g/m2.7] were
      evaluated in 661 participants from a community sample of black African ancestry
      (43% obese). RESULTS: BMI was inversely associated with Sokolow-Lyon voltages
      (partial r= -0.27, P < 0.0001) and no BMI-Cornell voltage relations were noted (P
      = 0.21). BMI was associated with voltage criteria that incorporate only limb lead
      recordings (r = 0.17-0.23), but these relations were weaker than BMI-LVMI
      relations (r = 0.36, P < 0.01 and P < 0.0001 for comparisons of r values). All
      electrocardiographic criteria were as strongly related to blood pressure as LVMI.
      Sokolow-Lyon voltage-LVMI relations were noted only after adjustments for BMI (P
      < 0.02) and Sokolow-Lyon voltages showed no performance for LVH detection.
      Cornell voltages showed significant performance in nonobese [area under receiver
      operating curve (AUC) = 0.67 +/- 0.04, P < 0.0005], but not in obese (AUC = 0.56
      +/- 0.04, P = 0.08). Electrocardiographic criteria which employ limb-lead
      recordings only (e.g. RaVL) showed better performance in nonobese than in obese
      (AUC = 0.75 +/- 0.04 and 0.59 +/- 0.04, respectively, P < 0.005 for comparison)
      and markedly reduced specificity for LVH detection in obese (76%) than in
      nonobese (92%, P < 0.0001) despite similar sensitivities (32 vs. 29%).
      CONCLUSION: In groups of black African ancestry, obesity contributes to a poor
      validity and performance of all voltage criteria for the detection of LVH. None
      of the current criteria are recommended for use in obesity.

PMID- 23169236
TI  - Hierarchical NiCo2O4@MnO2 core-shell heterostructured nanowire arrays on Ni foam
      as high-performance supercapacitor electrodes.
AB  - An advanced integrated electrode for high-performance supercapacitors has been
      designed by growing hierarchical NiCo(2)O(4)@MnO(2) core-shell heterostructured
      nanowire arrays on nickel foam. Such unique array nanoarchitectures exhibit
      remarkable electrochemical performance with high capacitance and desirable cycle
      life at high rates.

PMID- 23169237
TI  - Design and assembly of an ultra-light motorized microdrive for chronic neural
      recordings in small animals.
AB  - The ability to chronically record from populations of neurons in freely behaving
      animals has proven an invaluable tool for dissecting the function of neural
      circuits underlying a variety of natural behaviors, including navigation(1) ,
      decision making (2,3), and the generation of complex motor sequences(4,5,6).
      Advances in precision machining has allowed for the fabrication of light-weight
      devices suitable for chronic recordings in small animals, such as mice and
      songbirds. The ability to adjust the electrode position with small remotely
      controlled motors has further increased the recording yield in various behavioral
      contexts by reducing animal handling.(6,7) Here we describe a protocol to build
      an ultra-light motorized microdrive for long-term chronic recordings in small
      animals. Our design evolved from an earlier published version(7), and has been
      adapted for ease-of use and cost-effectiveness to be more practical and
      accessible to a wide array of researchers. This proven design (8,9,10,11) allows
      for fine, remote positioning of electrodes over a range of ~ 5 mm and weighs less
      than 750 mg when fully assembled. We present the complete protocol for how to
      build and assemble these drives, including 3D CAD drawings for all custom
      microdrive components.

PMID- 23169239
TI  - Ultrathin silica films on metals: the long and winding road to understanding the
      atomic structure.
AB  - This paper critically reviews the experimental and theoretical studies on the
      growth of ultrathin silica films onto metal single crystal substrates reported to
      date. The silica films on Mo(112) and Ru(0001) are discussed in more detail to
      demonstrate the key roles of the multi-technique approach and interplay between
      experiment and theory in the quest for understanding the atomic structure of the
      films. The results show the structural complexity and diversity of silica
      overlayers on metals, providing further information towards our understanding of
      the atomic structure, structural dynamics and physical and chemical properties of
      silica and related materials.

PMID- 23169240
TI  - Aortic wall shear stress in Marfan syndrome.
AB  - The aim of this study was to quantify changes in thoracic aortic wall shear
      stress (WSS) in asymptomatic patients with Marfan syndrome (MFS) compared with
      healthy controls. WSS in the thoracic aorta was quantified based on time-resolved
      3D phase contrast MRI with three-directional velocity encoding (4D flow MRI,
      temporal resolution ~44 ms, spatial resolution ~2.5 mm) in 24 patients with
      confirmed MFS (age = 18 +/- 12 years) and in 12 older healthy volunteers (age =
      25 +/- 3 years). Diameters of the thoracic aorta normalized to body surface area
      were similar for both groups. Peak systolic velocity, absolute WSS, time-averaged
      WSS, circumferential WSS, peak systolic WSS, and WSS eccentricity were calculated
      in eight analysis planes distributed along the thoracic aorta. Plane-wise
      comparison revealed significant differences between MFS patients and volunteers
      in the proximal ascending aorta for peak systolic velocities (1.11 +/- 0.23 m/s
      vs. 1.34 +/- 0.18 m/s, P = 0.004) and circumferential WSS (0.14 +/- 0.03 N/m(2)
      vs. 0.11 +/- 0.02 N/m(2), P = 0.007). WSS eccentricity was altered in most of the
      ascending aorta and proximal arch (P = 0.009-0.020). MFS patients demonstrated
      segmental differences in peak systolic WSS with a significantly higher WSS at the
      inner curvature in the proximal ascending aorta and at the anterior part in the
      more distal ascending aorta (P < 0.01). These findings indicate differences in
      WSS associated with MFS despite similar aortic dimensions compared to controls.

PMID- 23169241
TI  - Spiropyran main-chain conjugated polymers.
AB  - The first main-chain conjugated copolymers based on alternating spiropyran (SP)
      and 9,9-dioctylfluorene (F8) units synthesized via Suzuki polycondensation (SPC)
      are presented. The reaction conditions of SPC are optimized to obtain materials
      of type P(para-SP-F8) with appreciably high molecular weights up to M(w) ~ 100 kg
      mol(-1). (13)C NMR is used to identify the random orientation of the non
      symmetric SP unit in P(p-SP-F8). Ultrasound-induced isomerization of P(p-SP-F8)
      to the corresponding merocyanine form P(p-MC-F8) yields a deep-red solution. This
      isomerization reaction is followed by (1)H NMR in solution using sonication,
      whereby the color increasingly changes to deep red. The possibility to
      incorporate multiple SP units into main-chain polymers significantly broadens
      existing SP-based polymeric architectures.

PMID- 23169242
TI  - Electrophysiological study of medial and lateral branches of the superficial
      radial nerve.
AB  - INTRODUCTION: In this study we sought to establish a new technique for nerve
      conduction study (NCS) of medial and lateral branches of the superficial radial
      nerve (SRN). METHODS: Antidromic NCS were performed on 60 healthy subjects,
      recording the sensory nerve action potential (SNAP) from the dorsomedial and
      dorsolateral aspects of the phalanx of the thumb. The main trunk of SRN was also
      investigated. RESULTS: SNAPs were easily recorded in all subjects, and normative
      latency and amplitude data were collected. CONCLUSIONS: We propose a simple and
      reliable technique to investigate nerve conduction of the terminal branches of
      the SRN, which could be useful in some focal and systemic pathologies.

PMID- 23169238
TI  - Hepatitis C virus inhibits AKT-tuberous sclerosis complex (TSC), the mechanistic
      target of rapamycin (MTOR) pathway, through endoplasmic reticulum stress to
      induce autophagy.
AB  - Hepatitis C virus (HCV) is able to induce autophagy via endoplasmic reticulum
      (ER) stress, but the exact molecular signaling pathway is not well understood. We
      found that the activity of the mechanistic target of rapamycin complex 1 (MTORC1)
      was inhibited in Huh7 cells either harboring HCV-N (genotype 1b) full-genomic
      replicon or infected with JFH1 (genotype 2a) virus, which led to the activation
      of UNC-51-like kinase 1 (ULK1) and thus to autophagy. We then analyzed activity
      upstream of MTORC1, and found that both protein kinase, AMP-activated, alpha
      (PRKAA, including PRKAA1 and PRKAA2, also known as AMP-activated protein kinase,
      AMPKalpha) and AKT (refers to pan AKT, including three isoforms of AKT1-3, also
      known as protein kinase B, PKB) were inhibited by HCV infection. The inhibition
      of the AKT-TSC-MTORC1 pathway contributed to upregulating autophagy, but
      inhibition of PRKAA downregulated autophagy. The net effect on autophagy was from
      AKT, which overrode the inhibition effect from PRKAA. It was further found that
      HCV-induced ER stress was responsible for the inhibition of the AKT pathway.
      Metformin, a PRKAA agonist, inhibited HCV replication not only by activating
      PRKAA as previously reported, but also by activating AKT independently of the
      autophagy pathway. Taken together, our data suggested HCV inhibited the AKT-TSC
      MTORC1 pathway via ER stress, resulting in autophagy, which may contribute to the
      establishment of the HCV-induced autophagy.

PMID- 23169243
TI  - A feces collection paper does not enhance participation in a fecal immunochemical
      test-based colorectal cancer screening program: randomized clinical trial.
AB  - Discomfort with the collection of a stool sample is a frequently cited barrier
      for participation in fecal test-based colorectal cancer screening. The objective
      was to evaluate whether a feces collection paper enhances participation in a
      fecal immunochemical test (FIT)-based colorectal cancer screening program.
      Randomized clinical trial. Second round of a biannual Dutch FIT-based colorectal
      cancer screening program pilot. A random sample of 10 265 individuals from the
      general population, men and women aged 50-75 years at an average risk for
      colorectal cancer, was eligible for participation. Invitees were randomized to an
      FIT-only group (n=5136) or an FIT in combination with a feces collection paper
      group (n=5129). The main outcome measure was participation in screening. Overall,
      5367 tests of 10 265 were returned (52%). In the FIT-only group, 2694 tests were
      returned [52%; 95% confidence interval (CI): 51-54%] versus 2673 tests in the
      collection paper group (52%; 95% CI: 51-54%). This difference in the
      participation rate was not significant (relative risk: 0.99; 95% CI: 0.97-1.04).
      A feces collection paper does not increase participation rates in FIT-based
      colorectal cancer screening. Future studies should explore other ways of
      facilitating participation in colorectal cancer screening programs.

PMID- 23169244
TI  - Multiple single-nucleotide polymorphism-based risk model for clinical outcomes
      after allogeneic stem-cell transplantation, especially for acute graft-versus
      host disease.
AB  - BACKGROUND: We aimed to develop multiple single-nucleotide polymorphism (SNP)
      based risk models associated with the risk of transplant outcomes including graft
      versus-host disease (GVHD). METHODS: The study evaluated 259 SNPs in 53 genes in
      394 pairs of donors and recipients. In a discovery set (n=307 receiving related
      donor transplantation), overall survival, relapse-free survival (RFS), nonrelapse
      mortality, and acute or chronic GVHD were evaluated. RESULTS: Eight recipients'
      SNPs of IL2, IL6R, FAS, EDN1, TGFB1, and NFKBIA genes and 12 donors' SNPs of
      NOS1, IL1B, TGFB2, NOD2/CARD15, TNFRII, IL1R1, and FCGR2A genes were identified
      in univariate analyses. Risk models were generated using significant clinical
      variables and genetic SNP markers after filtering out through multivariate
      analyses. Then, we divided patients into four quartiles (25%, Q) according to
      their risks. The final models stratified patients into low-risk (Q1), moderate
      risk (Q2, Q3), and high-risk (Q4) groups in terms of overall survival (P<0.0001),
      RFS (P<0.0001), nonrelapse mortality (P=0.0043), and acute GVHD (P<0.0001), but
      not for chronic GVHD (P=0.763). External validation was performed in 87
      transplant pairs that received matched unrelated donor transplantation,
      especially for RFS (P=0.016) and acute GVHD (P=0.027). CONCLUSION: Risk models
      can improve prognostic stratification of patients according to their risk for
      transplant outcome.

PMID- 23169246
TI  - Light-induced stereospecific intramolecular [2+2]-cycloaddition of atropisomeric
      3,4-dihydro-2-pyridones.
AB  - Atropisomeric 3,4-dihydro-2-pyridones undergo stereospecific [2+2]
      photocycloaddition in solution with high stereoselectivity (ee > 98% and de >
      96%) in the product. The chiral transfer during phototransformation was
      rationalized based on the stability/reactivity of the biradical.

PMID- 23169245
TI  - Clinical-pathologic correlation between transperineal mapping biopsies of the
      prostate and three-dimensional reconstruction of prostatectomy specimens.
AB  - BACKGROUND: Extended transrectal ultrasound guided biopsies (TRUSB) of the
      prostate may not accurately convey true morphometric information and Gleason
      score (GS) of prostate cancer (PCa) and the clinical use of template-guided (5-mm
      grid) transperineal mapping biopsies (TPMBs) remains controversial. METHODS: We
      correlated the clinical-pathologic results of 1,403 TPMB cores obtained from 25
      men diagnosed with PCa with 64 cancer lesions found in their corresponding
      radical prostatectomy (RP) specimens. Special computer models of three
      dimensional, whole-mounted radical prostatectomy (3D-WMRP) specimens were
      generated and used as gold standard to determine tumor morphometric data. Between
      sample rates of upgrade and downgrade (highest GS and a novel cumulative GS) and
      upstage and downstage (laterality) were determined. Lesions >= 0.5 cm(3) or GS >=
      7 were considered clinically significant. RESULTS: From 64 separate 3D-WMRP
      lesions, 25 had significant volume (mean 1.13 cm(3)) and 39 were insignificant
      (mean 0.09 cm(3)) (P < 0.0001); 18/64 lesions were missed by TPMB, but only one
      was clinically significant with GS-8 (0.02 cm(3)). When comparing the cumulative
      GS of TPMB versus RP, 72% (n = 18) had identical scores, 12% (n = 3) were
      upgraded, and only 16% (n = 4) were downgraded. Laterality of TPMB and RP was
      strongly correlated, 80% same laterality, 4% were up-staged, and 16% down-staged.
      CONCLUSIONS: Our clinical-pathology correlation showed very high accuracy of TPMB
      with a 5-mm grid template to detect clinically significant PCa lesions as
      compared with 3D-WMRP, providing physicians and patients with a reliable
      assessment of grade and stage of disease and the opportunity to choose the most
      appropriate therapeutic options.

PMID- 23169249
TI  - Analysis of staff safety concerns.
AB  - The purpose of this project was to translate safety concerns extracted from
      written survey comments into actionable items. This project then served as the
      catalyst for resolving a number of significant safety issues in a performance
      improvement model and helped to create a reliable and efficient process for
      future thematic reviews.

PMID- 23169250
TI  - Incorporating bedside report into nursing handoff: evaluation of change in
      practice.
AB  - Nursing shift report on the medical-surgical units of a large teaching hospital
      was modified from a recorded report to a blend of both recorded and bedside
      components. Comparisons between baseline and postimplementation data indicated
      increased patient satisfaction and nurse perception of accountability and patient
      involvement but reduced nurse perceptions of efficiency and effectiveness of
      report. Patient falls at shift change and medication errors were reduced, whereas
      nurse overtime remained unchanged.

PMID- 23169251
TI  - Flexural rigidity measurements of biopolymers using gliding assays.
AB  - Microtubules are cytoskeletal polymers which play a role in cell division, cell
      mechanics, and intracellular transport. Each of these functions requires
      microtubules that are stiff and straight enough to span a significant fraction of
      the cell diameter. As a result, the microtubule persistence length, a measure of
      stiffness, has been actively studied for the past two decades(1). Nonetheless,
      open questions remain: short microtubules are 10-50 times less stiff than long
      microtubules(2-4), and even long microtubules have measured persistence lengths
      which vary by an order of magnitude(5-9). Here, we present a method to measure
      microtubule persistence length. The method is based on a kinesin-driven
      microtubule gliding assay(10). By combining sparse fluorescent labeling of
      individual microtubules with single particle tracking of individual fluorophores
      attached to the microtubule, the gliding trajectories of single microtubules are
      tracked with nanometer-level precision. The persistence length of the
      trajectories is the same as the persistence length of the microtubule under the
      conditions used(11). An automated tracking routine is used to create microtubule
      trajectories from fluorophores attached to individual microtubules, and the
      persistence length of this trajectory is calculated using routines written in
      IDL. This technique is rapidly implementable, and capable of measuring the
      persistence length of 100 microtubules in one day of experimentation. The method
      can be extended to measure persistence length under a variety of conditions,
      including persistence length as a function of length along microtubules.
      Moreover, the analysis routines used can be extended to myosin-based acting
      gliding assays, to measure the persistence length of actin filaments as well.

PMID- 23169252
TI  - Is the extracardiac conduit the preferred Fontan approach for patients with
      univentricular hearts? The extracardiac conduit is the preferred Fontan approach
      for patients with univentricular hearts.

PMID- 23169253
TI  - Is the extracardiac conduit the preferred Fontan approach for patients with
      univentricular hearts? The extracardiac conduit is not the preferred Fontan
      approach for patients with univentricular hearts.

PMID- 23169254
TI  - A shocking front nine: cardiac arrest on the golf course.

PMID- 23169255
TI  - Amelioration of high cardiac output and pulmonary hypertension by occlusion of
      congenital porto-systemic shunt.

PMID- 23169256
TI  - Simultaneous positron emission tomography/magnetic resonance imaging identifies
      sustained regional abnormalities in cardiac metabolism and function in stress
      induced transient midventricular ballooning syndrome: a variant of Takotsubo
      cardiomyopathy.

PMID- 23169257
TI  - Cardiokines: recent progress in elucidating the cardiac secretome.

PMID- 23169258
TI  - Letter by Cortese and Valgimigli regarding article, "Antithrombotic therapy in
      patients with chronic kidney disease".

PMID- 23169259
TI  - Adsorption-induced restructuring and early stages of carbon-nanotube growth on Ni
      nanoparticles.
AB  - Carbon adsorption on various Ni surfaces is investigated as a function of
      coverage via a combination of first-principles simulations and field emission
      microscope experiments. It is found that carbon can be efficiently stored as
      subsurface carbides, but with different energetics on differently oriented
      surfaces depending on their compactness and density of adsorption sites. In the
      resulting morphological reshaping, {113} facets are predicted to grow at the
      expense of {111} and {100} facets, in excellent agreement with experimental
      observations. Moreover, at high coverage on the {113} surface the carbon
      adsorption energy passes through a maximum after which a structural crossover is
      realized such that carbon atoms tend to ascend to the surface to form one
      dimensional chains (which are the precursors of graphitic nanostructures). This
      rationalizes the experimental observation of an incubation time between carbon
      storage and the beginning of catalytic growth, and provides insight into the
      early stages (nucleation mechanism) of carbon nanotubes on Ni nanoparticles.

PMID- 23169260
TI  - The accuracy of subjective clinical assessments of the patellar reflex.
AB  - INTRODUCTION: Measurement precision and accuracy of spinal reflexes plays an
      essential role in the clinical neurological examination. Reflexes are
      conventionally assessed either electromyographically or with rating scales. In
      this study we compared objective kinematic T-reflex and subjective assessments of
      patellar reflexes in 15 normal healthy subjects. METHODS: Randomized recordings
      of objectively quantified reflexes were rated by 24 medical students, 16 general
      practitioners, and 12 neurologists, using a visual analog scale and the NINDS and
      Mayo clinical reflex scales. RESULTS: For all groups of raters, Spearman rank
      correlations showed that subjective ratings significantly correlated with change
      of knee angle (R2 = 0.72-0.79, P < 0.001) and maximum T-reflex amplitude (R2 =
      0.84-0.94, P < 0.001). Stepwise multiple regression analysis showed that all
      subjective rater groups relied most on the change of knee angle to assess the
      reflex. CONCLUSIONS: These findings show that subjective assessments of reflexes
      using reflex rating scales correlate strongly with biomechanical and
      electromyographic measures.

PMID- 23169261
TI  - Effective phosphorescence quenching in borylated Pt(II) ppy-type phosphors and
      their application as I- ion sensors in aqueous medium.
AB  - The first example of phosphorescent I(-) ion sensors based on borylated Pt(II)
      ppy-type phosphors (Hppy = 2-phenylpyridine) was reported, which shows good
      selectivity and sensitivity.

PMID- 23169262
TI  - Safety of thromboprophylaxis after oncologic head and neck surgery. Study of 1018
      patients.
AB  - BACKGROUND: Deep venous thrombosis (DVT) and pulmonary embolism (PE) are
      significantly reduced with appropriate use of thromboprophylaxis and scarcely
      evaluated in patients undergoing oncologic head and neck surgery (OHNS). METHODS:
      A retrospective study on 1018 patients who underwent oncologic head and neck
      surgery. The records of patients with venous thromboembolism (VTE) or
      postoperative bleeding were reviewed for the cancer grading, management, previous
      known coagulopathy, anticoagulation, and general demographics. RESULTS: Of a
      total of 1018 patients undergoing oncologic head and neck surgery, 450 patients
      had no chemoprophylaxis and 568 received it. The rate of a VTE event in our
      cohort was 0%. Twelve patients presented with hematoma or bleeding from the
      surgical site, 11 in the group that received chemoprophylaxis (p = .006).
      CONCLUSIONS: Our analysis shows no benefit from chemoprophylaxis in oncologic
      head and neck surgery patients, with no VTE events. Our analysis shows higher
      rates of morbid side effects from using chemoprophylaxis, and we therefore
      conclude that chemoprophylaxis should not be routinely used.

PMID- 23169263
TI  - 1H NMR spectra of ethane-1,2-diol and other vicinal diols in benzene: GIAO/DFT
      shift calculations.
AB  - The proton NMR spectra of several 1,2-diols in benzene have been analysed so as
      to associate each magnetically nonequivalent proton with its chemical shift. The
      shifts and coupling constants of the OH and methylene protons of ethane-1,2-diol
      have been determined in a wide range of solvents. The conformer distribution and
      the proton NMR shifts of these 1,2-diols in benzene have been computed on the
      basis of density functional theory. The solvent is included using the integral
      equation-formalism polarizable continuum model implemented in Gaussian 09.
      Relative Gibbs energies for all stable conformers are calculated at the Perdew,
      Burke and Enzerhof (PBE)0/6-311 + G(d,p) level, and shifts are calculated using
      the gauge-including atomic orbital method with the PBE0/6-311 + G(d,p) geometry
      but using the cc-pVTZ basis set. Previous calculations on ethane-1,2-diol and
      propane-1,2-diol have been corrected and extended. New calculations on tert
      butylethane-1,2-diol, phenylethane-1,2-diol, butane-2,3-diols (dl and meso) and
      cyclohexane-1,2-diols (cis and trans) are presented. Overall, the computed NMR
      shifts are in good agreement with experimental values for the OH protons but
      remain systematically high for CH protons. Some results based on the Gaussian 03
      solvation model are included for comparison.

PMID- 23169264
TI  - Beckmann rearrangement of ketoximes induced by phenyl dichlorophosphate at
      ambient temperature.
AB  - Upon treatment with phenyl dichlorophosphate (PhOP=OCl(2)) in acetonitrile at
      ambient temperature, a variety of ketoximes underwent a Beckmann rearrangement in
      an effective manner to afford the corresponding amides in moderate to high
      yields.

PMID- 23169265
TI  - Chemical constituents from stem bark and roots of Clausena anisata.
AB  - Phytochemical investigations on the stem bark and roots of the tropical shrub
      Clausena anisata led to the isolation and characterization three carbazole
      alkaloids: girinimbine, murrayamine-A and ekeberginine; two peptide derivatives:
      aurantiamide acetate and N-benzoyl-L-phenylalaninyl-N-benzoyl-L-phenylalaninate;
      and a mixture of two phytosterols: sitosterol and stigmasterol. The structures of
      these compounds were established by nuclear magnetic resonance (1H-NMR, 13C-NMR,
      COSY, HSQC, HMQC, HMBC and NOESY) spectroscopy and electrospray ionization mass
      spectrometry (MS).

PMID- 23169266
TI  - On the catalytic effect of water in the intramolecular Diels-Alder reaction of
      quinone systems: a theoretical study.
AB  - The mechanism of the intramolecular Diels&#8211;Alder (IMDA) reaction of
      benzoquinone 1, in the absence and in the presence of three water molecules, 1w,
      has been studied by means of density functional theory (DFT) methods, using the
      M05-2X and B3LYP functionals for exploration of the potential energy surface
      (PES). The energy and geometrical results obtained are complemented with a
      population analysis using the NBO method, and an analysis based on the global,
      local and group electrophilicity and nucleophilicity indices. Both implicit and
      explicit solvation emphasize the increase of the polarity of the reaction and the
      reduction of activation free energies associated with the transition states (TSs)
      of this IMDA process. These results are reinforced by the analysis of the
      reactivity indices derived from the conceptual DFT, which show that the increase
      of the electrophilicity of the quinone framework by the hydrogen-bond formation
      correctly explains the high polar character of this intramolecular process. Large
      polarization at the TSs promoted by hydrogen-bonds and implicit solvation by
      water together with a high electrophilicity-nucleophilicity difference
      consistently explains the catalytic effects of water molecules.

PMID- 23169267
TI  - The NCTC 2544 IL-18 assay for the in vitro identification of contact allergens.
AB  - Assessment of allergenic potency of low-molecular-weight compounds is generally
      performed using animal models, such as the murine Local Lymph Node Assay (LLNA)
      and the Guinea Pig Maximization Test (GMT). Progress in understanding the
      mechanism of skin sensitization, including effects on the production of cytokines
      by different cell types within the skin, provides the opportunity to develop in
      vitro tests as an alternative to in vivo sensitization testing. This unit will
      describe a method for differentiating contact allergens from low-molecular-weight
      respiratory allergens and irritants, based on the selective induction of
      intracellular interleukin 18 (IL-18) in the human keratinocyte cell line NCTC
      2544. Similar results could also be obtained using primary human keratinocytes or
      other human keratinocyte cell lines, e.g., HaCaT, HPKII, etc. IL-18 was chosen
      because this cytokine has been demonstrated to favor Th-1-type immune responses
      by enhancing the secretion of pro-inflammatory mediators such as TNF-alpha, IL-8,
      and IFN-gamma, and to play a key proximal role in the induction of allergic
      contact dermatitis.

PMID- 23169268
TI  - Assessment of intestinal peristalsis in vitro.
AB  - The protocol detailed in this unit is designed to assess intestinal peristaltic
      motility in the isolated small intestine in vitro and to measure the effects of
      drugs able to interfere with gut propulsive activity. The procedure is based on
      Trendelenburg's classic technique, described at the beginning of the 20th century
      in the isolated guinea pig ileum and, later on, extended to other intestinal
      preparations from the same animal and other animal species. This unit illustrates
      the basic procedures for setting up the intestinal preparation, recording
      peristalsis under near-physiologic conditions, and testing the pharmaco
      toxicological effects of drugs and pollutants on the contractile behavior of the
      gut wall. The protocol allows evaluating the action of drugs affecting sensory
      and/or motor neurons of the enteric nervous system and how these neurons control
      the development of the motor program of the gut wall. This model can be exploited
      to investigate novel compounds undergoing preclinical development and both
      inhibitors and stimulants of gastrointestinal peristaltic activity, as well as
      environmental or alimentary pollutants, like xenobiotics and naturally-occurring
      toxins, endowed with noxious activity with regard to digestive functions.

PMID- 23169269
TI  - The vesicular transport assay: validated in vitro methods to study drug-mediated
      inhibition of canalicular efflux transporters ABCB11/BSEP and ABCC2/MRP2.
AB  - The canalicular membrane of hepatocytes contains several transport proteins that
      use the energy of ATP to efflux potentially toxic molecules to the bile. Probably
      the two most important proteins at this location are MRP2 and BSEP, which
      transport phase II conjugates of xenobiotics and endobiotics and conjugated bile
      salts, respectively. The impaired function of either of these transporter
      proteins reduces the clearance of the toxic conjugates, resulting in their
      accumulation in the hepatocytes and eventually the plasma. Conjugated bile salts
      and phase II metabolites are compounds with low passive permeability; therefore,
      the most commonly used test system to investigate MRP2- and BSEP-mediated
      transport processes is the vesicular transport assay. The concentration of probe
      substrates and inhibitors used in the experiment is close to their free
      concentration in the hepatocytes, providing an advantage when calculating kinetic
      parameters (K(m), K(i), V(max)). The protocols aim to assist scientists to set up
      a transport assay for a known or potential substrate and test small molecule
      inhibition of the transporters.

PMID- 23169270
TI  - Membrane vesicle ABC transporter assays for drug safety assessment.
AB  - The use of plasma membrane vesicles that overexpress the bile salt export pump
      (BSEP) or multidrug resistance-associated protein 2, 3, or 4 (MRP2-4) with an in
      vitro vacuum filtration system offers a rapid and reliable means for screening
      drug candidates for their effects on transporter function in hepatocytes and thus
      their potential for causing drug-induced liver injury (DILI). Comparison of
      transporter activity in the presence and absence of ATP allows for determination
      of a specific assay window for each transporter. This window is used to determine
      the degree to which each test compound inhibits transporter activity. This assay
      battery is helpful for prioritizing and rank-ordering compounds within a chemical
      series with respect to each other and in the context of known inhibitors of
      transporter activity and/or liver injury. This model can be used to influence the
      drug development process at an early stage and provide rapid feedback regarding
      the selection of compounds for advancement to in vivo safety evaluations. A
      detailed protocol for the high-throughput assessment of ABC transporter function
      is provided, including specific recommendations for curve-fitting to help ensure
      consistent results.

PMID- 23169271
TI  - Is this the end of the Emergency Department theatre?
AB  - In the UK, many emergency departments (EDs) were built with dedicated theatres
      reflecting surgical origins. This study assessed the number and type of
      procedures performed in such a facility over a 16-year period. A retrospective
      cohort study of ED theatre usage was carried out in Aberdeen Royal Infirmary from
      1995 to 2010. Cases were identified from theatre log books, and relevant
      demographics were extracted and analyzed. In total, 8785 procedures were
      performed, although this decreased from 1078 cases in 1995 to 214 cases in 2010.
      Common procedures included fracture manipulation, abscess drainage and foreign
      body removal. Use of ED theatre has reduced considerably. The reasons for this
      are complex, but may reflect a reduction in the surgical skill set of staff in
      the ED. Sound basic surgical skills are valuable to the emergency physician and
      further consideration should be given to how these are best acquired in the
      course of training. 

PMID- 23169272
TI  - Protein phosphatase 1, regulatory subunit 15B is a survival factor for ERalpha
      positive breast cancer.
AB  - Breast cancer is a heterogeneous disease at both the clinical and molecular
      levels. This heterogeneity may give rise to different therapy responses.
      Molecular profiling has facilitated identification of signatures for stratifying
      patients who would potentially benefit from given therapies. Previously, we
      reported on a subset of genes with the potential for predicting response of
      primary breast cancer to neoadjuvant chemotherapy. Herein, we report that
      patients with luminal (estrogen receptor alpha [ERalpha]-expressing) breast
      cancer were enriched for nonresponders. To identify novel factors that contribute
      to the survival of breast cancer cells, a loss-of-function screen was performed
      with a subset of genes overexpressed in patients with disease resistant to
      chemotherapy. This approach led us to identify protein phosphatase 1, regulatory
      subunit 15B (PPP1R15B) as a factor with a potentially essential role in the
      survival of ERalpha-positive breast cancer cells. Functional analyses showed that
      PPP1R15B depletion results in impaired proliferation due to unsuccessful
      transition of cells from G1 to S phase of the cell cycle, and apoptosis
      induction. Moreover, our data revealed a regulatory role for PPP1R15B in
      activating ERalpha. Furthermore, a high level of PPP1R15B mRNA expression was
      associated with poor outcome following tamoxifen-based therapy. Accordingly,
      knockdown of PPP1R15B expression sensitized tamoxifen-resistant MCF-7 breast
      cancer cells to tamoxifen while reducing ERalpha abundance in these cells. Our
      findings reveal a novel role for PPP1R15B in the survival and therapy response of
      ERalpha-positive breast cancer and may open new avenues for tumor subtype
      specific therapeutic strategies in the era of personalized medicine.

PMID- 23169274
TI  - Effectiveness of pesticide safety training and knowledge about pesticide exposure
      among Hispanic farmworkers.
AB  - BACKGROUND: Pesticide poisoning rates remain high among farmworkers despite
      programs aimed at reducing pesticide exposure. METHODS: A cross-sectional study
      was conducted among 187 Hispanic farmworkers in North Carolina. Farmworkers were
      interviewed to determine the association between pesticide safety training and
      knowledge about pesticides and use of personal protective equipment (PPE).
      RESULTS: Use of PPE was higher among farmworkers who reported wearing gloves
      reduced the harmful effects of pesticides (adjusted odds ratio, 5.73; 95%
      confidence interval, 2.20-14.92) and those who received pesticide safety training
      at the extension office or growers association (adjusted odds ratio, 44.62; 95%
      confidence interval, 3.96-503.33). CONCLUSION: Some farmworkers are still not
      using PPE. Evaluation of Environmental Protection Agency Worker Protection
      Standards pesticide safety training and requirements for providing PPE are
      crucial to encourage farm workers to use PPE.

PMID- 23169275
TI  - Health care expenditures, hospitalizations, and productivity associated with
      cancer in US employer settings.
AB  - OBJECTIVE: To assess outcomes of health care expenditures, hospitalizations, and
      productivity among employed persons with cancer in the United States from 2004 to
      2008. METHODS: Agency for Healthcare Research and Quality's Medical Expenditure
      Panel Survey data were used in this retrospective cross-sectional study of
      employed adults aged 18 years or older with any diagnosis of malignant neoplasms.
      Multivariate regression analyses assessed the study's outcomes according to
      prominent cancer types and other factors. RESULTS: Overall, 3.31 million employed
      persons had cancer annually, incurring productivity losses of approximately 33.4
      million disability days. Women's cancers and melanoma were associated with higher
      burdens of illness relative to other forms. CONCLUSIONS: This nationally
      representative investigation found that disability days in employed persons with
      cancer equates to 20% of health care expenditures. Resources present within small
      organizational settings may be especially important to consider when implementing
      programs to prevent and cure cancer.

PMID- 23169276
TI  - Reducing the incidence of short-term disability: testing the effectiveness of an
      absence prediction and prevention intervention using an experimental design.
AB  - OBJECTIVE: This multi-employer, prospective, randomized, controlled trial
      validated a quantitative model to identify employees at high risk of short-term
      disability (STD) and evaluated the impact of a health advocate nurse-led
      intervention on STD incidence. METHODS: Following prospective randomization, the
      control group received usual and customary services while the intervention group
      received usual and customary plus additional services from Cigna.* RESULTS: At
      the 12-month assessment, 16.8% of the intervention group had documented STD
      claims compared with 19.8% of the control group (P = 0.06). Duration of STD and
      return to work rate were not statistically different. CONCLUSION: While not
      statistically significant, these results suggest that the intervention for
      employees at high risk of STD achieves practical and clinical significance by
      achieving absolute and relative reductions in risk of STD of 3% and 15%,
      respectively.

PMID- 23169277
TI  - Pressure versus temperature effects on intramolecular electron transfer in mixed
      valence complexes.
AB  - Mixed-valence trinuclear carboxylates, [M(3)O(O(2)CR)(6)L(3)] (M = metal, L =
      terminal ligand), have small differences in potential energy between the
      configurations M(II)M(III)M(III)<=>M(III)M(II)M(III)<=>M(III)M(III)M(II), which
      means that small external changes can have large structural effects, owing to the
      differences in coordination geometry between M(2+) and M(3+) sites (e.g., about
      0.2 A for Fe-O bond lengths). It is well-established that the electron transfer
      (ET) between the metal sites in these mixed-valence molecules is strongly
      dependent on temperature and on the specific crystal environment; however,
      herein, for the first time, we examine the effect of pressure on the electron
      transfer. Based on single-crystal X-ray diffraction data that were measured at
      15, 90, 100, 110, 130, 160, and 298 K on three different crystals, we first
      unexpectedly found that our batch of Fe(3)O (O(2)CC(CH(3))(3))(6)(C(5)H(5)N)(3)
      (1) exhibited a different temperature dependence of the ET process than previous
      studies of compound 1 have shown. We observed a phase transition at around 130 K
      that was related to complete valence trapping and Hirshfeld surface analysis
      revealed that this phase transition was governed by a subtle competition between
      C-H???pi and pi???pi intermolecular interactions. Subsequent high-pressure single
      crystal X-ray diffraction at pressures of 0.15, 0.35, 0.45, 0.74, and 0.96 GPa
      revealed that it was not possible to trigger the phase transition (i.e., valence
      trapping) by a reduction of the unit-cell volume, owing to this external
      pressure. We conclude that modulation of the ET process requires anisotropic
      changes in the intermolecular interactions, which occur when various directional
      chemical bonds are affected differently by changes in temperature, but not by the
      application of pressure.

PMID- 23169278
TI  - HPV16 genetic variation and the development of cervical cancer worldwide.
AB  - BACKGROUND: Factors that favour a small proportion of HPV16 infections to
      progress to cancer are still poorly understood, but several studies have
      implicated a role of HPV16 genetic variation. METHODS: To evaluate the
      association between HPV16 genetic variants and cervical cancer risk, we designed
      a multicentre case-control study based on HPV16-positive cervical samples (1121
      cervical cancer cases and 400 controls) from the International Agency for
      Research on Cancer biobank. By sequencing the E6 gene, HPV16 isolates were
      classified into variant lineages and the European (EUR)-lineage isolates were
      subclassified by the common polymorphism T350G. RESULTS: Incidence of variant
      lineages differed between cases and controls in Europe/Central Asia (P=0.006,
      driven by an underrepresentation of African lineages in cases), and South/Central
      America (P=0.056, driven by an overrepresentation of Asian American/North
      American lineages in cases). EUR-350G isolates were significantly
      underrepresented in cervical cancer in East Asia (odds ratio (OR)=0.02 vs EUR
      350T; 95% confidence interval (CI)=0.00-0.37) and Europe/Central Asia (OR=0.42;
      95% CI=0.27-0.64), whereas the opposite was true in South/Central America
      (OR=4.69; 95% CI=2.07-10.66). CONCLUSION: We observed that the distribution of
      HPV16 variants worldwide, and their relative risks for cervical cancer appear to
      be population-dependent.

PMID- 23169279
TI  - Functional genomic screening to enhance oncolytic virotherapy.
AB  - Functional genomic screening has emerged as a powerful approach for understanding
      complex biological phenomena. Of the available tools, genome-wide RNA
      interference (RNAi) technology is unquestionably the most incisive, as it
      directly probes gene function. Recent applications of RNAi screening have been
      impressive. Notable amongst these are its use in elucidated mechanism(s) for
      signal transduction, various aspects of cell biology, tumourigenesis and
      metastasis, resistance to cancer therapeutics, and the host's response to a
      pathogen. Herein we discuss how recent RNAi screening efforts have helped turn
      our attention to the targetability of non-oncogene support pathways for cancer
      treatment, with a particular focus on a recent study that identified a non
      oncogene addiction to the ER stress response as a synergist target for oncolytic
      virus therapy (OVT). Moreover, we give our thoughts on the future of RNAi
      screening as a tool to enhance OVT and describe recent technical improvements
      that are poised to make genome-scale RNAi experiments more sensitive, less noisy,
      more applicable in vivo, and more easily validated in clinically relevant animal
      models.

PMID- 23169280
TI  - Identification of circulating microRNAs as diagnostic biomarkers for use in
      multiple myeloma.
AB  - BACKGROUND: Multiple myeloma is a plasma cell disorder that is characterised by
      clonal proliferation of malignant plasma cells in the bone marrow, monoclonal
      paraprotein in the blood or urine and associated organ dysfunction. It accounts
      for approximately 1% of cancers and 13% of haematological cancers. Myeloma arises
      from an asymptomatic proliferation of monoclonal plasma cells termed monoclonal
      gammopathy of undetermined significance (MGUS). METHODS: MicroRNA expression
      profiling of serum samples was performed on three patient groups as well as
      normal controls. Validation of the nine microRNAs detected as promising
      biomarkers was carried out using TaqMan quantitative reverse transcription PCR.
      MicroRNA levels in serum were normalised using standard curves to determine the
      numbers of microRNAs per MUl of serum. RESULTS: Three serum microRNAs, miR-720,
      miR-1308 and miR-1246, were found to have potential as diagnostic biomarkers in
      myeloma. Use of miR-720 and miR-1308 together provides a powerful diagnostic tool
      for distinguishing normal healthy controls, as well as patients with unrelated
      illnesses, from pre-cancerous myeloma and myeloma patients. In addition, the
      combination of miR-1246 and miR-1308 can distinguish MGUS from myeloma patients.
      CONCLUSION: We have developed a biomarker signature using microRNAs extracted
      from serum, which has potential as a diagnostic and prognostic tool for multiple
      myeloma.

PMID- 23169281
TI  - Prognostic significance of circumferential resection margin involvement following
      oesophagectomy for cancer and the predictive role of endoluminal ultrasonography.
AB  - BACKGROUND: The optimum multimodal treatment for oesophageal cancer, and the
      prognostic significance of histopathological tumour involvement of the
      circumferential resection margin (CRM+) are uncertain. The aims of this study
      were to determine the prognostic significance of CRM+ after oesophagectomy and to
      identify endosonographic (endoluminal ultrasonography (EUS)) features that
      predict a threatened CRM+. METHODS: Two hundred and sixty-nine consecutive
      patients underwent potentially curative oesophagectomy (103 surgery alone, 124
      neoadjuvant chemotherapy (CS) and 42 chemoradiotherapy (CRTS)). Primary outcome
      measures were disease-free survival (DFS) and overall survival (OS). RESULTS:
      CRM+ was reported in 98 (38.0%) of all, and in 90 (62.5%) of pT3 patients.
      Multivariate analysis of pathological factors revealed: lymphovascular invasion
      (HR 2.087, 95% CI 1.396-3.122, P<0.0001), CRM+ (HR 1.762, 95% CI 1.201-2.586,
      P=0.004) and lymph node metastasis count (HR 1.563, 95% CI 1.018-2.400, P=0.041)
      to be independently and significantly associated with DFS. Lymphovascular
      invasion (HR 2.160, 95% CI 1.432-3.259, P<0.001) and CRM+ (HR 1.514, 95% CI 1.000
      2.292, P=0.050) were also independently and significantly associated with OS.
      Multivariate analysis revealed EUS T stage (T3 or T4, OR 24.313, 95% CI 7.438
      79.476, P<0.0001) and use or not of CRTS (OR 0.116, 95% CI 0.035-0.382, P<0.0001)
      were independently and significantly associated with CRM+. CONCLUSION: A positive
      CRM was a better predictor of DFS and OS than standard pTNM stage.

PMID- 23169282
TI  - Dietary patterns and survival in German postmenopausal breast cancer survivors.
AB  - BACKGROUND: Research on the association between dietary patterns and breast
      cancer survival is very limited. METHODS: A prospective follow-up study was
      conducted in Germany, including 2522 postmenopausal breast cancer patients
      diagnosed in 2001-2005 with available food frequency questionnaire data. Vital
      status, causes of death, and recurrences were verified through the end of 2009.
      Principle component factor analysis was used to identify pre-diagnostic dietary
      patterns. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated
      with Cox proportional hazards models. RESULTS: Two major dietary patterns were
      identified: 'healthy' (high intakes of vegetables, fruits, vegetable oil,
      sauces/condiments, and soups/bouillons) and 'unhealthy' (high intakes of red
      meat, processed meat, and deep-frying fat). Increasing consumption of an
      'unhealthy' dietary pattern was associated with an increased risk of non-breast
      cancer mortality (highest vs lowest quartile: HR, 3.69; 95% CI, 1.66-8.17; P
      trend <0.001). No associations with breast cancer-specific mortality and breast
      cancer recurrence were found. The 'healthy' dietary pattern was inversely
      associated with overall mortality (HR, 0.74; 95% CI, 0.47-1.15; P-trend=0.02) and
      breast cancer recurrence (HR, 0.71; 95% CI, 0.48-1.06; P-trend=0.02) in stage I
      IIIa patients only. CONCLUSION: Increasing intake of an 'unhealthy' pre
      diagnostic dietary pattern may increase the risk of non-breast cancer mortality,
      whereas increasing intake of a 'healthy' pattern may reduce the risk of overall
      mortality and breast cancer recurrence.

PMID- 23169283
TI  - Parity as a cofactor for high-grade cervical disease among women with persistent
      human papillomavirus infection: a 13-year follow-up.
AB  - BACKGROUND: Several environmental factors have been associated with increased
      risks for cervical cancer. We examined whether reproductive history,
      contraceptive use, or sexual behaviour increase the risk for cervical
      intraepithelial neoplasia grade 3 or worse (CIN3+) among women with persistent
      human papillomavirus (HPV) infection. METHODS: A population-based cohort of women
      participated in a personal interview and underwent a gynaecological examination
      at which cervical specimens were obtained for HPV DNA testing. Follow-up
      information (~13 years) on cervical lesions was obtained from the Danish
      Pathology Data Bank. Women who had a high-risk HPV infection comprised the
      overall study population (n=1353). A subgroup of women with persistent high-risk
      HPV infection (n=312) was identified. Hazard ratios (HRs) for a diagnosis of
      CIN3+ and the corresponding 95% confidence intervals (CIs) were calculated.
      RESULTS: Women with persistent HPV infection who had given birth had a
      significantly increased risk for CIN3+ (HR=1.78; 95% CI: 1.07-2.94). No
      association was found with pregnancy, use of intrauterine devices, or sexual
      behaviour. Based on small numbers, women with persistent HPV infection had a
      decreased risk for CIN3+ with any use of oral contraceptives (HR=0.54; 95% CI:
      0.29-1.00). CONCLUSION: Childbirth increases the risk for subsequent CIN3+ among
      women with persistent HPV infection.

PMID- 23169284
TI  - A predictive role for noncancerous prostate cells: low connexin-26 expression in
      radical prostatectomy tissues predicts metastasis.
AB  - BACKGROUND: It is important to identify markers that predict whether prostate
      cancer will metastasise. The adjacent noncancerous cells (influenced by the
      tumour cells) may also express potential markers. The objective of this study was
      to determine the influence of cancer cells on noncancerous cells and to assess
      the value of the cell-communication protein connexin-26 (Cx26) as a marker to
      predict the development of metastasis. METHODS: The effect of conditioned medium
      (CM) from PrCa cells on in vitro noncancerous cell proliferation, migration and
      invasion and Cx26 expression was determined. Connexin-26 expression was
      investigated in prostatectomy tissues from 51 PrCa patients by
      immunohistochemistry and compared with various clinicopathological parameters.
      RESULTS: Proliferation, migration and invasion of noncancerous cells were
      influenced by CM from the PrCa cell lines. Importantly, a clear relation was
      found between low Cx26 expression in the noncancerous tissue in prostatectomy
      sections and the risk of development of metastasis (P<0.0002). Kaplan-Meier
      analysis showed a relation between low Cx26 expression in noncancerous tissues
      and time to biochemical recurrence (P=0.0002). CONCLUSION: Measuring Cx26
      expression in the adjacent noncancerous tissues (rather than cancer tissues) of
      prostatectomy sections could help to identify high-risk patients who may benefit
      from adjuvant therapy to decrease the risk of metastasis.

PMID- 23169285
TI  - Dietary intake of nitrate and nitrite and risk of renal cell carcinoma in the NIH
      AARP Diet and Health Study.
AB  - BACKGROUND: Nitrate and nitrite are present in many foods and are precursors of N
      nitroso compounds, known animal carcinogens and potential human carcinogens. We
      prospectively investigated the association between nitrate and nitrite intake
      from dietary sources and risk of renal cell carcinoma (RCC) overall and clear
      cell and papillary histological subtypes in the NIH-AARP Diet and Health Study.
      METHODS: Nitrate and nitrite intakes were estimated from a 124-item food
      frequency questionnaire. Over a mean follow-up of 9 years, we identified 1816 RCC
      cases (n=498, clear cell; n=115, papillary cell) among 491 841 participants. Cox
      proportional hazard regression was used to estimate hazard ratios (HRs) and 95%
      confidence intervals (CIs). RESULTS: Individuals in the highest quintile of
      nitrite intake from animal sources compared with those in the lowest quintile,
      had an increased risk of total RCC and clear cell subtype (HR=1.28, 95% CI, 1.10
      1.49 and HR=1.68, 95% CI, 1.25-2.27, respectively). Nitrite from processed meats
      and other animal sources were associated with increased clear cell adenocarcinoma
      risk (HR=1.33, 95% CI, 1.01-1.76 and HR=1.78, 95% CI, 1.34-2.36, respectively).
      We found no association for nitrite intake from plant sources or nitrate intake
      overall. CONCLUSION: Our findings suggest that nitrite from animal sources may
      increase the risk of RCC, particularly clear cell adenocarcinomas.

PMID- 23169286
TI  - Primary cervical cancer screening with HPV testing compared with liquid-based
      cytology: results of round 1 of a randomised controlled trial -- the HPV FOCAL
      Study.
AB  - BACKGROUND: Round 1 data of human papillomavirus (HPV) FOCAL, a three-arm,
      randomised trial, which aims to establish the efficacy of HPV DNA testing as a
      primary screen for cervical cancer, are presented. METHODS: The three arms are:
      Control arm - liquid based cytology with atypical squamous cells of unknown
      significance (ASC-US) triage with hrHPV testing; Intervention Arm - hrHPV at
      entry with liquid-based cytology (LBC) triage of hrHPV positives, with exit
      screen at 4 years; Safety check arm - hrHPV at entry with LBC triage of hrHPV
      positives with exit screen at 2 years. RESULTS: A total of 6154 women were
      randomised to the control arm and 12 494 to the HPV arms (intervention and safety
      check). In the HPV arm, the baseline cervical intraepithelial neoplasia (CIN)2+
      and CIN3+ rate was 9.2/1000 (95%CI; 7.4, 10.9) and 4.8/1000 (95%CI; 3.6, 6.1),
      which increased to 16.1/1000 (95%CI 13.2, 18.9) for CIN2+ and to 8.0/1000 (95%CI;
      5.9, 10.0) for CIN3+ after subsequent screening of HPV-DNA-positive/cytology
      negative women. Detection rate in the control arm remained unchanged after
      subsequent screening of ASC-US-positive/hrHPV DNA-negative women at 11.0/1000 for
      CIN2+ and 5.0/1000 for CIN3+. CONCLUSION: After subsequent screening of women who
      were either hrHPV positive/cytology negative or ASC-US positive/HPV negative,
      women randomised to the HPV arms had increased CIN2+ detection compared with
      women randomised to the cytology arm.

PMID- 23169287
TI  - Tumour-infiltrating FOXP3(+) lymphocytes are associated with cytotoxic immune
      responses and good clinical outcome in oestrogen receptor-negative breast cancer.
AB  - BACKGROUND: Regulatory T cells (Tregs) are commonly identified by expression of
      the transcription factor FOXP3 and are conventionally thought to promote cancer
      progression by suppressing anti-tumour immune responses. We examined the
      relationship between FOXP3(+) tumour-infiltrating lymphocytes (TIL) and prognosis
      in oestrogen receptor (ER)-negative breast cancer, a tumour subtype with poor
      clinical outcome in which TIL are abundant. METHODS: FOXP3(+) and CD8(+) TIL were
      assessed by immunohistochemistry in a cohort of 175 ER- breast tumours. Results
      were confirmed in an independent data set of 78 ER- breast tumours with
      publically available gene expression data. RESULTS: High FOXP3(+) TIL levels were
      strongly associated with prolonged recurrence-free survival (HR=0.461, P=0.0002),
      particularly among basal-like tumours (HR=0.280, P=0.0001), for which FOXP3
      status was independent of standard prognostic factors. Over 75% of FOXP3(+) TIL
      in triple negative breast tumours displayed a conventional CD4(+)CD25(+) Treg
      phenotype. Importantly, FOXP3(+) TIL were positively correlated with CD8(+)
      (cytotoxic) T cells (r(s)=0.76, P<0.0001), and were prognostically insignificant
      in tumours with low levels of CD8(+) TIL. These observations were confirmed in an
      independent cohort. CONCLUSION: In contrast with current dogma, we show for the
      first time that FOXP3(+) TIL are associated with robust anti-tumour immunity and
      favourable prognosis in ER- breast cancer.

PMID- 23169288
TI  - Metabolic syndrome and hepatocellular carcinoma risk.
AB  - BACKGROUND: Hepatocellular carcinoma (HCC) has been associated to diabetes and
      obesity, but a possible association with the metabolic syndrome (MetS) and its
      potential interaction with hepatitis is open to discussion. METHODS: We analysed
      data from an Italian case-control study, including 185 HCC cases and 404
      controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were computed from
      unconditional logistic regression models. RESULTS: Among the MetS components,
      diabetes and obesity (i.e, body mass index (BMI)>=30 kg m(-2)) were positively
      associated to HCC risk, with ORs of 4.33 (95% CI, 1.89-9.86) and 1.97 (95% CI,
      1.03-3.79), respectively. The ORs for the MetS were 4.06 (95% CI, 1.33-12.38)
      defining obesity as BMI>=25, and 1.92 (95% CI, 0.38-9.76) defining it as BMI>=30.
      The risk increased with the number of MetS components, up to an almost four-fold
      excess risk among subjects with >=2 MetS factors. Among subjects without chronic
      infection with hepatitis B and/or C, the OR for those with >=2 MetS components
      was over six-fold elevated. There was no consistent association in subjects with
      serological evidence of hepatitis B and/or C infection. CONCLUSION: This study
      found that the risk of HCC increases with the number of MetS components in
      subjects not chronically infected with hepatitis viruses.

PMID- 23169289
TI  - CXCR7 receptors facilitate the progression of colon carcinoma within lung not
      within liver.
AB  - BACKGROUND: Liver and lung metastases are the predominant cause of colorectal
      cancer (CRC)-related mortality. Chemokine-receptor pairs have a critical role in
      determining the metastatic progression of tumours. Our hypothesis was that
      disruption of CXCR7/CXCR7 ligands axis could lead to a decrease in CRC
      metastases. METHODS: Primary tumours and metastatic tissues from patients with
      CRC were tested for the expression of CXCR7 and its ligands. Relevance of
      CXCR7/CXCR7 ligands for CRC metastasis was then investigated in mice using small
      pharmacological CXCR7 antagonists and CRC cell lines of human and murine origins,
      which - injected into mice - enable the development of lung and liver metastases.
      RESULTS: Following injection of CRC cells, mice treated daily with CXCR7
      antagonists exhibited a significant reduction in lung metastases. However, CXCR7
      antagonists failed to reduce the extent of liver metastasis. Moreover, there were
      subtle differences in the expression of CXCR7 and its ligands between lung and
      liver metastases. CONCLUSION: Our study suggests that the activation of CXCR7 on
      tumour blood vessels by its ligands may facilitate the progression of CRC within
      lung but not within liver. Moreover, we provide evidence that targeting the CXCR7
      axis may be beneficial to limit metastasis from colon cancer within the lungs.

PMID- 23169290
TI  - Analysis of gene alterations of mitochondrial DNA D-loop regions to determine
      breast cancer clonality.
AB  - BACKGROUND: It has been a challenge to determine breast cancer clonality
      accurately. The aim of the present study was to assess methods using formalin
      fixed paraffin-embedded (FFPE) tissue to differentiate new primary tumours from
      true recurrences that are associated with poorer prognoses and often require more
      aggressive treatment. METHODS: We investigated the novel method of analysing gene
      alterations of mitochondrial DNA D-loop region (GAMDDL) and compared it with the
      conventional method of analysing the X-chromosome-linked human androgen receptor
      (HUMARA). The FFPE sections of primary and secondary breast cancers, the non
      neoplastic mammary gland, and lymph nodes were examined. RESULTS: Informative
      rates for HUMARA, GAMDDL, and combined analyses were 42.1%, 76.9%, and 89.5%,
      respectively. All of the 10 contralateral breast cancers were determined to be
      non-clonal. In contrast, 3 out of 8 (37.5%) of the ipsilateral secondary tumours
      shared a clonal origin with the primary tumour and were classified as true
      recurrences, whereas 4 out of 8 (50%) were classified as new primary tumours.
      CONCLUSION: GAMDDL analysis represents a novel and useful molecular method for
      examining the precise cell lineages of primary and secondary tumours, and was
      more accurate than HUMARA in determining clonality.

PMID- 23169291
TI  - Suppression of activin A signals inhibits growth of malignant pleural
      mesothelioma cells.
AB  - BACKGROUND: Activins control the growth of several tumour types including
      thoracic malignancies. In the present study, we investigated their expression and
      function in malignant pleural mesothelioma (MPM). METHODS: The expression of
      activins and activin receptors was analysed by quantitative PCR in a panel of MPM
      cell lines. Activin A expression was further analysed by immunohistochemistry in
      MPM tissue specimens (N=53). Subsequently, MPM cells were treated with activin A,
      activin receptor inhibitors or activin-targeting siRNA and the impact on cell
      viability, proliferation, migration and signalling was assessed. RESULTS:
      Concomitant expression of activin subunits and receptors was found in all cell
      lines, and activin A was overexpressed in most cell lines compared with non
      malignant mesothelial cells. Similarly, immunohistochemistry demonstrated intense
      staining of tumour cells for activin A in a subset of patients. Treatment with
      activin A induced SMAD2 phosphorylation and stimulated clonogenic growth of
      mesothelioma cells. In contrast, treatment with kinase inhibitors of activin
      receptors (SB-431542, A-8301) inhibited MPM cell viability, clonogenicity and
      migration. Silencing of activin A expression by siRNA oligonucleotides further
      confirmed these results and led to reduced cyclin D1/3 expression. CONCLUSION:
      Our study suggests that activin A contributes to the malignant phenotype of MPM
      cells via regulation of cyclin D and may represent a valuable candidate for
      therapeutic interference.

PMID- 23169292
TI  - EGFR pathway biomarkers in erlotinib-treated patients with advanced pancreatic
      cancer: translational results from the randomised, crossover phase 3 trial AIO
      PK0104.
AB  - BACKGROUND: We aimed to identify molecular epidermal growth factor receptor
      (EGFR) tissue biomarkers in pancreatic cancer (PC) patients treated with the anti
      EGFR agent erlotinib within the phase 3 randomised AIO-PK0104 study. METHODS: AIO
      PK0104 was a multicenter trial comparing gemcitabine/erlotinib followed by
      capecitabine with capecitabine/erlotinib followed by gemcitabine in advanced PC;
      primary study end point was the time-to-treatment failure after first- and second
      line therapy (TTF2). Translational analyses were performed for KRAS exon 2
      mutations, EGFR expression, PTEN expression, the EGFR intron 1 and exon 13 R497K
      polymorphism (PM). Biomarker data were correlated with TTF, overall survival (OS)
      and skin rash. RESULTS: Archival tumour tissue was available from 208 (74%) of
      the randomised patients. The KRAS mutations were found in 70% (121 out of 173) of
      patients and exclusively occurred in codon 12. The EGFR overexpression was
      detected in 89 out of 181 patients (49%) by immunohistochemistry (IHC), and 77
      out of 166 patients (46%) had an EGFR gene amplification by fluorescence in-situ
      hybridisation (FISH); 30 out of 171 patients (18%) had a loss of PTEN expression,
      which was associated with an inferior TTF1 (first-line therapy; HR 0.61, P=0.02)
      and TTF2 (HR 0.66, P=0.04). The KRAS wild-type status was associated with
      improved OS (HR 1.68, P=0.005); no significant OS correlation was found for EGFR
      IHC (HR 0.96), EGFR-FISH (HR 1.22), PTEN-IHC (HR 0.77), intron 1 (HR 0.91) or
      exon 13 R497K PM (HR 0.83). None of the six biomarkers correlated with the
      occurrence of skin rash. CONCLUSION: The KRAS wild-type was associated with an
      improved OS in erlotinib-treated PC patients in this phase 3 study; it remains to
      be defined whether this association is prognostic or predictive.

PMID- 23169293
TI  - The hormonal profile of benign breast disease.
AB  - BACKGROUND: Limited information exists about the endocrine milieu of benign
      breast disease (BBD), a documented breast cancer risk factor. We compared blood
      levels of estrogens, testosterone and insulin-like growth factor-1 (IGF-1)
      between BBD patients by histological type and women without breast pathology.
      METHODS: We studied 578 BBD patients and 178 healthy women in Athens, Greece, who
      provided blood samples, and completed interviewer-administered questionnaires.
      RESULTS: Of the BBD patients, 254 had non-proliferative disease, 268
      proliferative disease without atypia and 56 atypical hyperplasia. Comparing BBD
      patients with healthy women, the per cent differences (and 95% confidence
      intervals) for blood hormones, among pre-menopausal and peri/post-menopausal
      women, respectively, were: 22.4% (-4.0%, 56.1%) and 32.0% (5.6%, 65.1%) for
      estradiol; 26.2% (10.1%, 44.8%) and 30.9% (16.8%, 46.6%) for estrone; 19.5%
      (3.1%, 38.4%) and 16.5% (-5.0%, 42.9%) for testosterone; and -5.2% (-13.8%, 4.4%)
      and -12.1% (-19.8%, -3.6%) for IGF-1. Steroid hormones tended to be higher in
      proliferative compared with non-proliferative BBD. CONCLUSIONS: Circulating
      steroid hormones tend to be higher among women with BBD than women with no breast
      pathology and higher in proliferative than non-proliferative disease; these
      patterns are more evident among peri/post-menopausal women. In peri/post
      menopausal women IGF-1 was lower among women with BBD compared with healthy
      women.

PMID- 23169294
TI  - Early detection of cancer in the general population: a blinded case-control study
      of p53 autoantibodies in colorectal cancer.
AB  - BACKGROUND: Recent reports from cancer screening trials in high-risk populations
      suggest that autoantibodies can be detected before clinical diagnosis. However,
      there is minimal data on the role of autoantibody signatures in cancer screening
      in the general population. METHODS: Informative p53 peptides were identified in
      sera from patients with colorectal cancer using an autoantibody microarray with
      15-mer overlapping peptides covering the complete p53 sequence. The selected
      peptides were evaluated in a blinded case-control study using stored serum from
      the multimodal arm of the United Kingdom Collaborative Trial of Ovarian Cancer
      Screening where women gave annual blood samples. Cases were postmenopausal women
      who developed colorectal cancer following recruitment, with 2 or more serum
      samples preceding diagnosis. Controls were age-matched women with no history of
      cancer. RESULTS: The 50 640 women randomised to the multimodal group were
      followed up for a median of 6.8 (inter-quartile range 5.9-8.4) years. Colorectal
      cancer notification was received in 101 women with serial samples of whom 97 (297
      samples) had given consent for secondary studies. They were matched 1 : 1 with 97
      controls (296 serial samples). The four most informative peptides identified
      25.8% of colorectal cancer patients with a specificity of 95%. The median lead
      time was 1.4 (range 0.12-3.8) years before clinical diagnosis. CONCLUSION: Our
      findings suggest that in the general population, autoantibody signatures are
      detectable during preclinical disease and may be of value in cancer screening. In
      colorectal cancer screening in particular, where the current need is to improve
      compliance, it suggests that p53 autoantibodies may contribute towards risk
      stratification.

PMID- 23169295
TI  - Upregulation of ERCC1 and DPD expressions after oxaliplatin-based first-line
      chemotherapy for metastatic colorectal cancer.
AB  - BACKGROUND: The updated randomised phase 2/3 FIRIS study demonstrated the
      noninferiority of IRIS (irinotecan and S-1) to FOLFIRI (irinotecan, folinic acid,
      and 5-FU) for metastatic colorectal cancer. Meanwhile, in the subset analysis
      including patients who previously have undergone oxaliplatin-containing
      chemotherapy, the IRIS group showed longer survival than the FOLFIRI group.
      However, the molecular mechanism underlying this result is still unknown.
      METHODS: The National Cancer Institute 60 (NCI60) cell line panel data were
      utilised to build the hypothesis. A total of 45 irinotecan-naive metastatic
      colorectal cancer patients who had undergone hepatic resection were included for
      the validation study. The mRNA expressions of excision repair cross-complementing
      group 1 (ERCC1), dihydropyrimidine dehydrogenase (DPD), and topoisomerase-1
      (TOP1) were evaluated by quantitative RT-PCR. The expressions of ERCC1 and DPD
      were also evaluated by immunohistochemistry. RESULTS: Sensitivity to oxaliplatin
      in 60 cell lines was significantly correlated with that of 5-FU. Resistant cells
      to oxaliplatin showed significantly higher ERCC1 and DPD expression than
      sensitive cells. In validation study, ERCC1 and DPD but not TOP1 expressions in
      cancer cells were significantly higher in FOLFOX (oxaliplatin, folinic acid, and
      5-FU)-treated patients (N=24) than nontreated patients (N=21). The ERCC1 and DPD
      protein expressions were also significantly higher in FOLFOX-treated patients.
      CONCLUSION: The ERCC1 and DPD expression levels at both mRNA and protein levels
      were significantly higher in patients with oxaliplatin as a first-line
      chemotherapy than those without oxaliplatin. The IRIS regimens with the DPD
      inhibitory fluoropyrimidine may show superior activity against DPD-high tumours
      (e.g., tumours treated with oxaliplatin) compared with FOLFIRI.

PMID- 23169297
TI  - Evidence for downregulation of the negative regulator SPRED2 in clinical prostate
      cancer.
AB  - BACKGROUND: SPRED1 and 2 are key negative regulators of MAPK signalling in
      mammalian cells. Here, we investigate the expression and functional role of
      SPREDs in prostate cancer. METHODS: A transcriptome bank of microdissected grade
      specific primary cancers was constructed and interrogated for transcript
      expression of prostate cancer genes, known negative signalling regulators as well
      as SPRED1 and 2. The effect of SPRED2 manipulation was tested in in vitro assays.
      RESULTS: In a panel of 5 benign glands and 15 tumours, we observed concomitant
      downregulation of the negative regulators SEF and DUSP1 in tumours with
      increasing Gleason grade. Profiling in the same cohorts revealed downregulation
      of SPRED2 mRNA in tumours compared with benign glands (P<0.05). By contrast,
      SPRED1 expression remained unchanged. This observation was further validated in
      two additional separate cohorts of microdissected tumours (total of n=10 benign
      and n=58 tumours) with specific downregulation of SPRED2 particularly in higher
      grade tumours. In functional assays, SPRED2 overexpression reduced ERK
      phosphorylation and inhibited prostate cancer cell proliferation and migration in
      response to different growth factors and full-media stimulation (P<0.001).
      Conversely, SPRED2 suppression by siRNA enhanced the mitogenic response to growth
      factors and full media (P<0.001). CONCLUSION: These data suggest first evidence
      that SPRED2 is downregulated in prostate cancer and warrants further
      investigation as a potential tumour-suppressor gene.

PMID- 23169296
TI  - A triplet combination with irinotecan (CPT-11), oxaliplatin (LOHP), continuous
      infusion 5-fluorouracil and leucovorin (FOLFOXIRI) plus cetuximab as first-line
      treatment in KRAS wt, metastatic colorectal cancer: a pilot phase II trial.
AB  - BACKGROUND: We conducted an open-label, pilot phase II trial to evaluate the
      efficacy and safety of FOLFOXIRI plus cetuximab as first-line treatment of
      patients with metastatic colorectal cancer (mCRC). METHODS: Thirty patients with
      KRAS wild-type mCRC, <70 years and with performance status 0-1 were included in
      the trial. RESULTS: Complete and partial responses were observed in 4 (13.3%) and
      17 (56.7%) patients, respectively (overall response rate (ORR)=70%; 95%
      confidence interval (CI): 53.6%-86.4%); 8 patients (26.7%) had stable disease and
      1 had progressive disease. The median time to tumour progression was 10.2 months
      (95% CI: 7.1-13.4) and the overall median survival time was 30.3 months (95% CI:
      18.8-41.9). Secondary R0 resection was performed in 11 (37%) patients. Grade 3 or
      4 diarrhoea and neutropenia were observed in 16 (53%) and 7 (23.3%) patients,
      respectively, and febrile neutropenia observed in 2 (6.6%) patients.
      Neurotoxicity grade 2 or 3 was reported in 7 (23.3%) and in 2 (6.7%) patients,
      respectively, and grade 3 rush was reported in 1 patient. CONCLUSION: The
      FOLFOXIRI/cetuximab combination presented increased activity in terms of response
      rate and R0 secondary liver metastases resection, and merits further
      investigation, especially in patients with initially unresectable disease
      confined to the liver.

PMID- 23169298
TI  - Smoking and the risk of prostate cancer in the European Prospective Investigation
      into Cancer and Nutrition.
AB  - BACKGROUND: Smoking is not associated with prostate cancer incidence in most
      studies, but associations between smoking and fatal prostate cancer have been
      reported. METHODS: During 1992 and 2000, lifestyle information was assessed via
      questionnaires and personal interview in a cohort of 145,112 European men. Until
      2009, 4623 incident cases of prostate cancer were identified, including 1517
      cases of low-grade, 396 cases of high grade, 1516 cases of localised, 808 cases
      of advanced disease, and 432 fatal cases. Multivariable Cox proportional hazards
      regression models were used to examine the association of smoking status, smoking
      intensity, and smoking duration with the risk of incident and fatal prostate
      cancer. RESULTS: Compared with never smokers, current smokers had a reduced risk
      of prostate cancer (RR=0.90, 95% CI: 0.83-0.97), which was statistically
      significant for localised and low-grade disease, but not for advanced or high
      grade disease. In contrast, heavy smokers (25+ cigarettes per day) and men who
      had smoked for a long time (40+ years) had a higher risk of prostate cancer death
      (RR=1.81, 95% CI: 1.11-2.93; RR=1.38, 95% CI: 1.01-1.87, respectively).
      CONCLUSION: The observation of an increased prostate cancer mortality among heavy
      smokers confirms the results of previous prospective studies.

PMID- 23169299
TI  - Phase I and pharmacodynamic study of high-dose NGR-hTNF in patients with
      refractory solid tumours.
AB  - BACKGROUND: NGR-hTNF exploits the peptide asparagine-glycine-arginine (NGR) for
      selectively targeting tumour necrosis factor (TNF) to CD13-overexpressing tumour
      vessels. Maximum-tolerated dose (MTD) of NGR-hTNF was previously established at
      45 MUg m(-2) as 1-h infusion, with dose-limiting toxicity being grade 3 infusion
      related reactions. We explored further dose escalation by slowing infusion rate
      (2-h) and using premedication (paracetamol). METHODS: Four patients entered each
      of 12 dose levels (n=48; 60-325 MUg m(-2)). Pharmacokinetics, soluble TNF
      receptors (sTNF-R1/sTNF-R2), and volume transfer constant (K(trans)) by dynamic
      imaging (dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI)) were
      assessed pre- and post-treatment. RESULTS: Common related toxicity included grade
      1/2 chills (58%). Maximum-tolerated dose was not reached. Both C(max) (P<0.0001)
      and area under the plasma concentration-time curve (P=0.0001) increased
      proportionally with dose. Post-treatment levels of sTNF-R2 peaked significantly
      higher than sTNF-R1 (P<0.0001). Changes in sTNF-Rs, however, did not differ
      across dose levels, suggesting a plateau effect in shedding kinetics. As best
      response, 12/41 evaluable patients (29%) had stable disease. By DCE-MRI, 28/37
      assessed patients (76%) had reduced post-treatment K(trans) values (P<0.0001),
      which inversely correlated with NGR-hTNF C(max) (P=0.03) and baseline K(trans)
      values (P<0.0001). Lower sTNF-R2 levels and greater K(trans) decreases after
      first cycle were associated with improved survival. CONCLUSION: asparagine
      glycine-arginine-hTNF can be safely escalated at doses higher than MTD and
      induces low receptors shedding and early antivascular effects.

PMID- 23169301
TI  - Homogenates of skeletal muscle injected with snake venom inhibit myogenic
      differentiation in cell culture.
AB  - INTRODUCTION: Viperid snakebite envenomings are characterized by muscle necrosis
      and a deficient regenerative response. METHODS: Homogenates from gastrocnemius
      muscles of mice injected with the venom of the snake Bothrops asper or with 2
      tissue-damaging toxins were added to cultures of C2C12 myogenic cells. Myoblasts
      proliferation and fusion were assessed. Venom was detected by immunoassay in
      mouse muscle during the first week after injection. RESULTS: Homogenates from
      venom-injected muscle induced a drop in the number of proliferating myoblasts and
      a complete elimination of myotube formation. The inhibitory effect induced by
      homogenates from venom-injected mice was abrogated by preincubation of the
      homogenate with antivenom antibodies but not with control antibodies. This
      finding provides evidence that the effect is due to the action of venom in the
      tissue. CONCLUSIONS: Our observations suggest that traces of venom in muscle
      tissue might inhibit myotube formation and preclude a successful regenerative
      response.

PMID- 23169302
TI  - One-photon excited luminescence of single gold particles diffusing in solution
      under pulsed illumination.
AB  - Here we report on the visible luminescence of single gold nanospherical particles
      diffusing in water excited by a pulsed-laser at 488 nm. The signal studied by
      fluorescence correlation spectroscopy does not display the expected
      characteristics. The main deviation is obtained for the diffusion time that
      depends on the laser irradiance. Additional advanced methods of measurements have
      been implemented to further characterize the emission. These methods have allowed
      us to demonstrate that the luminescence does not blink even in the picosecond
      domain and that it does not photobleach either. The comparison between the
      signals obtained under pulsed and continuous excitations at the same wavelength
      suggests that the increase in the particle temperature plays a role in the non
      linear increase in the luminescence intensity with the excitation power. As in
      the case of two-photon excited luminescence, it implies that a model describing
      the luminescence process for a single particle diffusing in liquid must take into
      account the whole system composed of the gold particle, the capping ligands and
      the surrounding water.

PMID- 23169300
TI  - High expression of N-acetylglucosaminyltransferase IVa promotes invasion of
      choriocarcinoma.
AB  - BACKGROUND: Gestational trophoblastic diseases (GTDs) are related to
      trophoblasts, and human chorionic gonadotropin (hCG) is secreted by GTDs as well
      as normal placentas. However, the asparagine-linked sugar chains on hCG contain
      abnormal biantennary structures in invasive mole and choriocarcinoma, but not
      normal pregnancy or hydatidiform mole. N-acetylglucosaminyltransferase-IV (GnT
      IV) catalyses beta1,4-N-acetylglucosamine branching on asparagine-linked
      oligosaccharides, which are consistent with the abnormal sugar chain structures
      on hCG. METHODS: We investigated GnT-IVa expression in GTDs and placentas by
      immunohistochemistry, western blot, and RT-PCR. We assessed the effects of GnT
      IVa knockdown in choriocarcinoma cells in vitro and in vivo. RESULTS: The GnT-IVa
      was highly expressed in trophoblasts of invasive mole and choriocarcinoma, and
      moderately in extravillous trophoblasts during the first trimester, but not in
      hydatidiform mole or other normal trophoblasts. The GnT-IVa knockdown in
      choriocarcinoma cells significantly reduced migration and invasive capacities,
      and suppressed cellular adhesion to extracellular matrix proteins. The extent of
      beta1,4-N-acetylglucosamine branching on beta1 integrin was greatly reduced by
      GnT-IVa knockdown, although the expression of beta1 integrin was not changed. In
      vivo studies further demonstrated that GnT-IVa knockdown suppressed tumour
      engraftment and growth. CONCLUSION: These findings suggest that GnT-IVa is
      involved in regulating invasion of choriocarcinoma through modifications of the
      oligosaccharide chains of beta1 integrin.

PMID- 23169303
TI  - Two-photon optogenetic toolbox for fast inhibition, excitation and bistable
      modulation.
AB  - Optogenetics with microbial opsin genes has enabled high-speed control of
      genetically specified cell populations in intact tissue. However, it remains a
      challenge to independently control subsets of cells within the genetically
      targeted population. Although spatially precise excitation of target molecules
      can be achieved using two-photon laser-scanning microscopy (TPLSM) hardware, the
      integration of two-photon excitation with optogenetics has thus far required
      specialized equipment or scanning and has not yet been widely adopted. Here we
      take a complementary approach, developing opsins with custom kinetic, expression
      and spectral properties uniquely suited to scan times typical of the raster
      approach that is ubiquitous in TPLSMlaboratories. We use a range of culture,
      slice and mammalian in vivo preparations to demonstrate the versatility of this
      toolbox, and we quantitatively map parameter space for fast excitation,
      inhibition and bistable control. Together these advances may help enable broad
      adoption of integrated optogenetic and TPLSMtechnologies across experimental
      fields and systems.

PMID- 23169305
TI  - Morphology-controllable 1D-3D nanostructured TiO2 bilayer photoanodes for dye
      sensitized solar cells.
AB  - Morphology-controlled bilayer TiO(2) nanostructures consisting of one-dimensional
      (1D) nanowire bottom arrays and a three-dimensional (3D) dendritic microsphere
      top layer were synthesized via a one-step hydrothermal method. These novel 1D-3D
      bilayer photoanodes demonstrated the highest energy conversion efficiency of 7.2%
      for rutile TiO(2) dye-sensitized solar cells to date, with TiCl(4) post
      treatment.

PMID- 23169304
TI  - High symptom burden prior to radiation therapy for head and neck cancer: a
      patient-reported outcomes study.
AB  - BACKGROUND: As a first step toward developing effective strategies to control
      symptoms associated with head and neck cancer (HNC) and its treatment, we sought
      to describe the pattern of symptoms experienced before radiation therapy.
      METHODS: Subjects completed the MD Anderson Symptom Inventory-Head and Neck
      Module before beginning radiation therapy. RESULTS: In all, 270 patients
      participated. Symptom severity and interference varied between treatment-naive
      patients and those with prior treatment. Cluster analyses revealed that 33% of
      patients had high symptom burden. Symptoms most often rated moderate-to-severe
      were fatigue, sleep disturbance, distress, pain, and problems chewing and
      swallowing. Poorer performance status, higher T classification, and receipt of
      previous treatment correlated with higher symptom burden. CONCLUSIONS: A
      substantial proportion of patients were experiencing high symptom burden. Because
      few interventions currently exist for several of the most problematic symptoms,
      research in symptom reduction that targets the pattern of symptoms described here
      is greatly needed.

PMID- 23169306
TI  - The level of consumer information about health insurance in Nanjing, China.
AB  - The Chinese government is considering a (regulated) competitive healthcare
      system. Sufficient consumer information is a crucial pre-condition to benefit
      from such a change. We conducted a survey on the level of consumer information
      regarding health insurance among the insured population in Nanjing, China in
      2009. The results from descriptive analysis and binary logistic regression
      demonstrate that the current level of consumer information about health insurance
      is low. The level of consumer information is positively correlated with the
      subscribers' motivation to obtain the information and its availability. The level
      of searching for health insurance information is also low; moreover, even upon
      searching, the chance of finding relevant information is less than 25%. We
      conclude that the level of consumer information is currently insufficient in
      China. If the Chinese government is determined to adopt market mechanisms in the
      healthcare sector, it should take the lead in making valid and reliable
      information publicly available and easily accessible.

PMID- 23169307
TI  - Endoscopic ultrasound elastography for differentiation of benign and malignant
      pancreatic masses:  a systemic review and meta-analysis.
AB  - BACKGROUND: Endoscopic ultrasound (EUS) elastography is a novel method for
      visualization of tissue elasticity modulus during a conventional EUS examination.
      The reported yield of EUS elastography for the differentiation of benign and
      malignant pancreatic masses has shown variable results. The objective of this
      study was to assess the accuracy of EUS elastography by pooling data of available
      trials. METHODS: The Medline, PubMed, Embase, and Cochrane Central Trials
      databases were used to retrieve all the studies that assessed the diagnostic
      accuracy of EUS elastography for the differentiation of benign and malignant
      pancreatic masses. Pooling was carried out using a fixed-effect model when
      significant heterogeneity was not present; otherwise, the random-effect model was
      used. If there were less than four studies using the same diagnostic standard,
      forest plots were constructed without pooling. RESULTS: In six studies using the
      qualitative color pattern as the diagnostic standard, the sensitivity was 99%
      (95% confidence interval 98-100%) and the specificity was 74% (95% confidence
      interval 65-82%). The area under the curve under the summary receiver-operating
      characteristic was 0.9624. In three studies using the quantitative hue histogram
      value as the diagnostic standard, the sensitivity was 85-93% and the specificity
      was 64-76%. CONCLUSION: EUS elastography is a promising noninvasive technique for
      the differentiation of pancreatic masses with a high sensitivity, and may prove
      to be a valuable complementary method to EUS-FNA.

PMID- 23169308
TI  - Elevated levels of the long pentraxin 3 in paracetamol-induced human acute liver
      injury.
AB  - OBJECTIVES: Pentraxin 3 (PTX3) is a long pentraxin with diverse humoral innate
      immune functions. The aims of this study were to measure levels of PTX3 and C
      reactive protein (CRP), a hepatocyte-derived short pentraxin, in patients after
      acute liver injury. METHODS: PTX3 and CRP levels were measured in a total of 60
      patients [48 paracetamol overdose (POD), 12 non-POD]. PTX3 expression was
      assessed by immunohistochemical analysis in explanted liver tissue. RESULTS:
      Admission PTX3 levels were significantly higher in POD acute liver failure (ALF)
      patients compared with POD non-ALF patients (P=0.0005) and non-POD patients
      (P=0.004). PTX3 levels in POD patients who died or required orthotopic liver
      transplantation (OLT, n=14) were significantly higher compared with those in
      spontaneous survivors (n=34, P=0.0011). The area under the receiver operator
      characteristic for PTX3 for death/OLT in POD patients was 0.80 (95% confidence
      interval 0.67-0.93). PTX3 levels were significantly higher in those POD patients
      who developed the systemic inflammatory response syndrome (P=0.001). Conversely,
      admission CRP levels were significantly lower in POD compared with non-POD
      patients (P=0.011), with no significant differences between survivors and
      nonsurvivors. After emergency OLT, PTX3 levels fell markedly; in contrast, CRP
      levels rapidly increased. Immunohistochemical analysis showed PTX3 expression in
      sinusoidal lining cells of a normal liver, infiltrating inflammatory cells in
      patients with ALF, and in a membranous distribution on injured hepatocytes in POD
      patients. CONCLUSION: Increased PTX3 levels are associated with adverse outcomes
      following POD, suggesting that the humoral innate immune system plays an
      underrecognized role in this condition.

PMID- 23169309
TI  - Overview of molecular pathways in inflammatory bowel disease associated with
      colorectal cancer development.
AB  - Patients with long-standing inflammatory bowel disease (IBD) are at a higher risk
      of developing colorectal cancer (CRC). This risk increases with the longer
      duration of colitis, greater extent of inflammation, a family history of CRC,
      severity of bowel inflammation, and a coexistent primary sclerosing cholangitis.
      The cornerstone for comprehending the development of CRC in IBD and hence early
      detection is based on the understanding of the molecular pathways of IBD itself.
      At a molecular level, the pathogenesis of CRC is related to understanding the
      inflammatory changes and involves multiple inter-related pathways including (i)
      genetic alterations (e.g. chromosomal and microsatellite instability and
      hypermethylation), (ii) mucosal inflammatory mediators (e.g. COX-2, interleukin
      6, interleukin-23, tumor necrosis factor-alpha, nuclear factor-kappaB, and
      chemokines), (iii) changes in the expression of receptors on the epithelial
      cells, and (iv) oxidant stress, mucosal breakdown, and intestinal microbiota. The
      aim of this review is to provide an evidence-based approach for the role of
      chronic inflammatory mechanisms and the molecular basis of these mechanisms in
      the development of CRC. Therefore, understanding the molecular basis of CRC is an
      important step for the identification of new biomarkers that can help in the
      early detection of CRC in these patients.

PMID- 23169310
TI  - Surgical management of gallbladder disease in the very elderly:  are we operating
      them at the right time?
AB  - BACKGROUND: As life expectancy rises worldwide and the prevalence of gallstones
      increases with age, the number of very elderly patients requiring treatment for
      gallstone diseases is increasing. The aim of this study was to compare the
      results of cholecystectomy in patients 80 years or older according to different
      clinical presentations. METHODS: This is a retrospective study of 81 patients 80
      years or older. Indications for surgery were stratified into three groups:
      outpatients (symptomatic chronic cholecystitis), inpatients (complicated
      gallstone diseases), and urgent patients (acute cholecystitis). Data analysis
      included age, sex, the American Society of Anesthesiologists score, indication
      for surgery, length of hospital stay, morbidity, and mortality. RESULTS: The mean
      age of the patients was 83.9 (range 80-94 years); there were 34 (42%) men. Thirty
      patients were operated on for acute cholecystitis. Patients in the urgency group
      significantly required the ICU more often, required a longer hospital stay, and
      had more complications, with 32% mortality. No differences were found between
      inpatients and outpatients, with both groups presenting low morbidity, no
      mortality, and the same postoperative length of stay. CONCLUSION: More than 80%
      of the patients were operated on because of complicated gallstone disease.
      Although the outcomes of patients undergoing semielective cholecystectomy were
      similar to those of patients treated as outpatients, patients operated with acute
      cholecystitis presented extremely high morbidity and mortality rates. Thus, we
      can only recommend that early elective cholecystectomy be performed in elderly
      patients as soon as they are found to have symptomatic gallstones. Also, further
      trials are required to elucidate the optimal management of acute cholecystitis in
      elderly patients.

PMID- 23169311
TI  - Low hepatitis B envelope antigen seroconversion rate in chronic hepatitis B
      patients on long-term entecavir 0.5 mg daily in routine clinical practice.
AB  - AIM: Data from registration trials with highly selective patients have shown that
      hepatitis B envelope antigen (HBeAg)-positive patients with chronic hepatitis B
      respond well to entecavir (ETV) 0.5 mg daily, with an HBeAg seroconversion rate
      of 21% at 12 months. However, there are varying data on the treatment outcomes of
      ETV 0.5 mg daily in routine clinical settings, with seroconversion rates at 12
      months ranging from 8 to 48% in studies limited to 44-90 patients from centers in
      Asia, Europe, and South America. MATERIALS AND METHODS: In the present study, we
      examined long-term treatment efficacy and tolerability in 136 consecutive
      treatment-naive HBeAg-positive chronic hepatitis B patients treated between
      January 2005 and January 2011 with ETV 0.5 mg daily at community clinics and
      tertiary centers in the USA. The primary study end point was HBeAg
      seroconversion. RESULTS: Sixty-one percent of HBeAg-positive patients were men,
      mean age 39 +/- 12 years, median hepatitis B virus DNA 7.48 (3.7-9.8) log10
      IU/ml, median alanine aminotransferase 67 (14-1077) U/l, and median treatment
      duration 18 (6-60) months. At months 12, 24, and 36, complete viral suppression
      rates were 41, 66, and 85% and HBeAg seroconversion rates were 4.8, 20, and 30%,
      respectively. No patients experienced adverse events or developed genotypic
      resistance to ETV. CONCLUSION: In clinical settings, ETV is highly tolerable and
      potent at suppressing hepatitis B viremia; however, the rates of HBeAg
      seroconversion appear to be much lower than those reported, highlighting the
      importance of appropriate counseling and planning for long-term therapy.

PMID- 23169312
TI  - Risk factors associated with colorectal flat adenoma detection.
AB  - OBJECTIVES: Colorectal flat adenomas have been associated with a higher risk of
      colorectal malignancy. We describe demographic characteristics and endoscopic
      findings in patients with colorectal flat adenomas. METHODS: In total, 1934
      consecutive patients undergoing colonoscopy were prospectively included. Polyp
      shape was classified according to the Japanese classification. Chromoendoscopy
      was applied whenever a flat lesion was suspected. Indications for colonoscopy,
      demographic data, and characteristics of neoplastic lesions were recorded.
      Patients were classified as follows: group 1, no adenomas (n=1250); group 2, only
      protruding adenomas (n=427); group 3, protruding and flat adenomas (n=118); and
      group 4, only flat adenomas (n=139). RESULTS: Approximately one in every 10
      patients (13.2%) had flat adenomas. Among them, concomitant protruding adenomas
      were identified in approximately half of the cases. In multivariate analysis, age
      older than 50 years [odds ratio (OR)=1.62; 95% confidence interval (CI)=1.08
      2.43, P=0.02], protruding adenomas (OR=2.17; 95% CI=1.65-2.87, P<0.001), follow
      up colonoscopy for polyps or cancer (OR=2.22; 95% CI=1.59-3.10, P<0.001),
      screening colonoscopy (OR=1.60, 95% CI=1.15-2.22, P=0.005), and specifically
      trained endoscopist (OR=2.02, 95% CI=1.53-2.68, P<0.001) were associated
      independently with flat adenoma detection. CONCLUSION: Flat adenomas have
      specific demographic factors that might help to improve detection. Particularly,
      age older than 50 years, colorectal neoplasia surveillance, and the presence of
      protruding adenomas should alert endoscopists to the possible presence of these
      lesions. Trained endoscopists may offer a greater chance of detecting these
      lesions.

PMID- 23169313
TI  - Suffocation deaths associated with use of infant sleep positioners--United
      States, 1997-2011.
AB  - Unintentional suffocation is the leading cause of injury death among children
      aged <1 year in the United States, accounting for nearly 1,000 infant deaths
      annually. Since 1984, an estimated fourfold increase has been observed in
      accidental suffocation and strangulation in bed, with many of these deaths linked
      to unsafe sleep environments. Infant sleep positioners (ISPs) are devices
      intended to keep an infant in a specific position while sleeping, yet ISPs have
      been reported to have been present in the sleep environment in some cases of
      unintentional infant suffocation. Some specific ISPs have been cleared by the
      Food and Drug Administration (FDA) for the management of gastroesophageal reflux
      or plagiocephaly (asymmetry of the skull). However, many unapproved ISPs have
      been marketed to the general public with claims of preventing sudden infant death
      syndrome (SIDS), improving health, and enhancing sleep comfort. To characterize
      infant deaths associated with ISPs, FDA, the U.S. Consumer Product Safety
      Commission (CPSC), and CDC examined information reported to CPSC about 13 infant
      deaths in the past 13 years associated with the use of ISPs. In this case series,
      all infants but one were aged <=3 months, and most were placed on their sides to
      sleep. Many were found prone (i.e., lying on their abdomens). Accompanying
      medical issues included prematurity and intercurrent respiratory illnesses. When
      providing guidance for parents of newborns, health-care providers need to
      emphasize the importance of placing infants to sleep on their backs in a safe
      sleep environment. This includes reminders about the American Academy of
      Pediatrics (AAP) recommendations against side sleep position, ISPs and pillows,
      comforters, and other soft bedding.

PMID- 23169314
TI  - Chronic obstructive pulmonary disease among adults--United States, 2011.
AB  - Chronic obstructive pulmonary disease (COPD) is a group of progressive,
      debilitating respiratory conditions, including emphysema and chronic bronchitis,
      characterized by difficulty breathing, lung airflow limitations, cough, and other
      symptoms. COPD often is associated with a history of cigarette smoking and is the
      primary contributor to mortality caused by chronic lower respiratory diseases,
      which became the third leading cause of death in the United States in 2008.
      Despite this substantial disease burden, state-level data on the prevalence of
      COPD and associated health-care resource use in the United States have not been
      available for all states. To assess the state-level prevalence of COPD among
      adults, the impact of COPD on their quality of life, and the use of health-care
      resources by those with COPD, CDC analyzed data from the 2011 Behavioral Risk
      Factor Surveillance System (BRFSS). Among BRFSS respondents in all 50 states, the
      District of Columbia (DC), and Puerto Rico, 6.3% reported having been told by a
      physician or other health professional that they had COPD. In addition to the
      screening question asked of all respondents, 21 states, DC, and Puerto Rico
      elected to include an optional COPD module. Among persons who reported having
      COPD and completed the optional module, 76.0% reported that they had been given a
      diagnostic breathing test, 64.2% felt that shortness of breath impaired their
      quality of life, and 55.6% were taking at least one daily medication for their
      COPD. Approximately 43.2% of them reported visiting a physician for COPD-related
      symptoms in the previous 12 months, and 17.7% had either visited an emergency
      department or been admitted to a hospital for their COPD in the previous 12
      months. Continued surveillance for COPD, particularly at state and local levels,
      is critical to 1) identify communities that likely will benefit most from
      awareness and outreach campaigns and 2) evaluate the effectiveness of public
      health efforts related to the prevention, treatment, and control of the disease.

PMID- 23169315
TI  - Multistate outbreak of Salmonella serotype Bovismorbificans infections associated
      with hummus and tahini--United States, 2011.
AB  - On September 27, 2011, three clinical isolates of Salmonella enterica serotype
      Bovismorbificans with indistinguishable pulsed-field gel electrophoresis (PFGE)
      patterns were identified by the District of Columbia Public Health Laboratory
      (PHL). Human infection with S. Bovismorbificans is rare in the United States.
      Through query of PulseNet, the national molecular subtyping network for foodborne
      disease surveillance, six additional cases with indistinguishable PFGE patterns
      were identified in three states (Maryland, Michigan, and Virginia) during the
      prior 60 days. All nine patients had eaten at restaurants in the District of
      Columbia (DC) or northern Virginia <2 weeks before illness onset. This report
      summarizes the investigation led by the DC Department of Health (DOH), in which
      23 cases of S. Bovismorbificans infections were identified among persons from
      seven states and DC, with illness onset during August 19-November 21, 2011. On
      May 30, 2012, traceback indicated that contaminated tahini (sesame seed paste)
      used in hummus prepared at a Mediterranean-style restaurant in DC was a plausible
      source of Salmonella infections. DOH restricted the sale of hummus and prohibited
      the use of hummus ingredients in other food items at implicated restaurants to
      prevent further illness. This investigation also illustrates challenges
      associated with ingredient-driven outbreaks and the value of PulseNet for
      identifying clusters of cases that are geographically dispersed.

PMID- 23169316
TI  - Indoor air quality at nine large-hub airports with and without designated smoking
      areas--United States, October-November 2012.
AB  - Secondhand smoke (SHS) exposure causes death and disease among nonsmoking adults
      and children. Adopting policies that completely prohibit smoking in all indoor
      areas is the only effective way to eliminate involuntary SHS exposure. Among the
      29 large-hub U.S. airports, five currently allow smoking in specifically
      designated indoor areas accessible to the general public. In 2011, these five
      airports had a combined passenger boarding of approximately 110 million. To
      assess indoor air quality at the five large-hub U.S. airports with designated
      indoor smoking areas and compare it with the indoor air quality at four large-hub
      U.S. airports that prohibit smoking in all indoor areas, CDC measured the levels
      of respirable suspended particulates (RSPs), a marker for SHS. The results of
      this assessment determined that the average level of RSPs in the smoking
      permitted areas of these five airports was 16 times the average level in
      nonsmoking areas (boarding gate seating sections) and 23 times the average level
      of RSPs in the smoke-free airports. The average RSP level in areas adjacent to
      the smoking-permitted areas was four times the average level in nonsmoking areas
      of the five airports with designated smoking areas and five times the average
      level in smoke-free airports. Smoke-free policies at the state, local, or airport
      authority levels can eliminate involuntary exposure to SHS inside airports and
      protect employees and travelers of all ages from SHS.

PMID- 23169317
TI  - Hantavirus pulmonary syndrome in visitors to a national park--Yosemite Valley,
      California, 2012.
AB  - On August 16, 2012, the California Department of Public Health announced two
      confirmed cases of hantavirus pulmonary syndrome (HPS) in California residents
      who had stayed overnight in Yosemite National Park, launching an investigation by
      the National Park Service, California Department of Public Health, and CDC. On
      August 27, Yosemite National Park announced two additional cases, and by October
      30, 10 cases had been confirmed.

PMID- 23169318
TI  - Genetic sequence variants in vitamin D metabolism pathway genes, serum vitamin D
      level and outcome in head and neck cancer patients.
AB  - Although some studies have reported associations between serum vitamin D level
      and prognosis in several cancers, others have found associations between genetic
      sequence variants (GSVs) in the vitamin D metabolism pathway genes and outcomes
      in various cancers including head and neck cancer (HNC). We comprehensively
      evaluated the association and interaction of GSVs in vitamin D metabolism pathway
      genes and their regulatory effects on circulatory serum vitamin D level in HNC
      outcome. We systemically evaluated the association of 89 tagging and candidate
      based GSVs in six major vitamin D metabolism pathway genes (VDR, GC, CYP24A1,
      CYP27A1, CYP27B1 and CYP2R1) and the circulating serum vitamin D level with
      overall survival (OS) and second primary cancer (SPC) in 522 Stages I-II
      radiation-treated patients with HNC. For OS: median follow-up time was 8 years;
      for SPC, 4.4 years. The most common subsite was the larynx (84%). Three hundred
      and twelve patients were alive at the end of follow-up for OS. SPCs were
      diagnosed in 108 patients and were primarily of lung (46%). Serum vitamin D
      levels were significantly lower in patients carrying the minor alleles of
      GC:rs4588 and CYP2R1:rs10500804. CYP24A1:rs2296241 was significantly associated
      with OS and CYP2R1:rs1993116 was with SPC. These two GSVs remained significantly
      associated after adjusting for serum vitamin D level and important clinical
      factors. GSVs in the vitamin D metabolism pathway genes were associated with
      disease outcomes in HNC patients; however, these GSVs are different from those
      affecting serum vitamin D levels.

PMID- 23169320
TI  - Long-term follow-up of DDH patients who underwent open reduction without a
      postoperative cast.
AB  - We present the results - assessed after bony maturation - of an early anterior
      approach open reduction performed using our modified technique on 49 hips at 6-24
      months of age. We start postoperative functional treatment using a Pavlik harness
      and an abduction splint, abandoning plaster cast. Secondary surgeries were
      performed in 11 hips (22.4%) at 3-7 years of age. Our results were 'satisfactory'
      (Severin Grade I, II) in 96% of the cases. According to the joints' Severin
      Grade, the total hip replacement probability at an early age is 8.16% in our
      series. Our principles and practice, introduced in 1980 in terms of secondary
      surgeries, are in total harmony with the recent literature.

PMID- 23169319
TI  - Head-to-head comparison of subcutaneous abatacept versus adalimumab for
      rheumatoid arthritis: findings of a phase IIIb, multinational, prospective,
      randomized study.
AB  - OBJECTIVE: There is a need for comparative studies to provide evidence-based
      treatment guidance for biologic agents in rheumatoid arthritis (RA). Therefore,
      this study was undertaken as the first head-to-head comparison of subcutaneous
      (SC) abatacept and SC adalimumab, both administered along with background
      methotrexate (MTX), for the treatment of RA. METHODS: Patients with active RA who
      were naive to treatment with biologic agents and had an inadequate response to
      MTX were randomly assigned to receive 125 mg SC abatacept weekly or 40 mg SC
      adalimumab biweekly, both given in combination with MTX, in a 2-year study. The
      primary end point was treatment noninferiority, assessed according to the
      American College of Rheumatology 20% improvement response (ACR20) at 1 year.
      RESULTS: Of the 646 patients who were randomized and treated, 86.2% receiving SC
      abatacept and 82% receiving SC adalimumab completed 12 months of treatment. At 1
      year, 64.8% of patients in the SC abatacept group and 63.4% in the SC adalimumab
      group demonstrated an ACR20 response; the estimated difference between groups was
      1.8% (95% confidence interval -5.6%, 9.2%), thus demonstrating the noninferiority
      of abatacept compared to adalimumab. All efficacy measures showed similar results
      and kinetics of response between treatments. The rate of radiographic
      nonprogression (defined as a total modified Sharp/van der Heijde score [SHS] less
      than or equal to the smallest detectable change) was 84.8% for SC abatacept
      treated patients and 88.6% for SC adalimumab-treated patients, while the mean
      change from baseline in the total SHS was 0.58 and 0.38, respectively. In the SC
      abatacept and SC adalimumab groups, the incidence of serious adverse events
      (SAEs) was 10.1% and 9.1%, respectively, and the rate of serious infections was
      2.2% and 2.7%, respectively. In patients treated with SC abatacept, the frequency
      of discontinuations due to AEs was 3.5% and discontinuations due to SAEs was
      1.3%, while in patients treated with SC adalimumab, the frequencies were 6.1% and
      3%, respectively. Injection site reactions occurred in 3.8% of patients receiving
      SC abatacept compared to 9.1% of patients receiving SC adalimumab (P=0.006).
      CONCLUSION: The results demonstrate that SC abatacept and SC adalimumab have
      comparable efficacy in patients with RA, as shown by similar kinetics of response
      and comparable inhibition of radiographic progression over 1 year of treatment.
      The safety was generally similar, other than the occurrence of significantly more
      local injection site reactions in patients treated with SC adalimumab.

PMID- 23169323
TI  - Intra- and internerve cross-sectional area variability: new ultrasound measures.

PMID- 23169324
TI  - Synthesis and two-photon absorption property characterizations of small dendritic
      chromophores containing functionalized quinoxaliniod heterocycles.
AB  - A series of star-shaped multi-polar chromophores (compounds 1-3) containing
      functionalized quinoxaline and quinoxalinoid (indenoquinoxaline and
      pyridopyrazine) units has been synthesized and characterized for their two-photon
      absorption (2PA) properties both in the femtosecond and the nanosecond time
      domain. Under our experimental conditions, these model fluorophores are found to
      manifest strong and wide-dispersed two-photon absorption in the near-infrared
      region. It is demonstrated that molecular structures with multi-branched pi
      frameworks incorporating properly functionalized quinoxalinoid units would
      possess large molecular nonlinear absorptivities within the studied spectral
      range. Effective optical-power attenuation and stabilization behaviors in the
      nanosecond time domain of a selected representative dye molecule (i.e., compound
      2) from this model compound set were also investigated and the results indicate
      that such structural motif could be a useful approach for the molecular design
      toward strong two-photon-absorbing material systems for quick-responsive and
      broadband optical-suppressing-related applications, particularly to confront long
      laser pulses.

PMID- 23169325
TI  - The accuracy of women's reports of their partner's male circumcision status in
      Rakai, Uganda.
AB  - We assessed whether women had accurate knowledge of their partners' male
      circumcision status using survey data (2010-2011) from Rakai, Uganda, and
      examined characteristics of women who misreported male circumcision status. Among
      couples in which men were uncircumcised (n = 1744), 8.2% women misreported; and
      among couples in which men were confirmed circumcised (n = 759), 1.2% women
      misreported. Younger women were 2.2 times more likely to misreport compared with
      older women. Misreporting was not associated with other sociodemographics or
      behavioural characteristics. If women are to act as advocates for male
      circumcision acceptance, there is a need to educate women, particularly younger
      women about the nature and recognition of male circumcision.

PMID- 23169326
TI  - Initiating antiretroviral therapy when presenting with higher CD4 cell counts
      results in reduced loss to follow-up in a resource-limited setting.
AB  - OBJECTIVE: In August 2011, South Africa expanded its adult antiretroviral therapy
      (ART) guidelines to allow treatment initiation at CD4 cell values 350 cells/MUl
      or less. Mortality and morbidity are known to be reduced when initiating at
      higher CD4 levels; we explored the impact on patient loss to follow-up. DESIGN:
      An observational cohort study. METHODS: We analyzed routine data of 1430 adult
      patients initiating ART from April to December 2010 from a Johannesburg primary
      healthcare clinic offering ART initiation at CD4 cell count 350 cells/MUl or less
      since 2010. We compared loss to follow-up (>=3 months late for the last scheduled
      visit), death, and incident tuberculosis within 1 year of ART initiation for
      those initiating at CD4 cell values 200 or less versus 201-350 cells/MUl.
      RESULTS: : Half (52.0%) of patients presented in the lower CD4 cell group [<=200
      cells/MUl, median: 105 cells/MUl, interquartile range (IQR): 55-154] and
      initiated ART, and 48.0% in the higher group (CD4 cell count 201-350 cells/MUl,
      median: 268 cells/MUl, IQR: 239-307). The proportion of women and pregnant women
      was greater in the high CD4 cell group; the lower CD4 cell group included more
      patients with prevalent tuberculosis. Among men and nonpregnant women, initiating
      at 201-350 cells/MUl was associated with 26-42% reduced loss to follow-up
      compared to those initiating 200 cells/MUl or less. We found no CD4 cell effect
      among pregnant women. Risk of mortality [adjusted hazard ratio (aHR) 0.34, 95%
      confidence interval (CI) 0.13-0.84] and incident tuberculosis (aHR 0.44, 95% CI
      0.23-0.85) was lower among the higher CD4 cell group. CONCLUSION: This is one of
      the first studies from a routine clinical setting to demonstrate South Africa's
      2011 expansion of ART treatment guidelines can be enacted without increasing
      program attrition.

PMID- 23169327
TI  - Markers of microbial translocation and risk of AIDS-related lymphoma.
AB  - BACKGROUND: Depletion of gut-associated lymphocytes by HIV infection facilitates
      microbial translocation, which may contribute to non-Hodgkin lymphoma (NHL) risk
      via chronic immune activation and B-cell hyperstimulation. METHOD: We therefore
      examined associations of four microbial translocation markers with subsequent NHL
      risk in a case-control study nested within four prospective cohort studies of HIV
      infected individuals. Prediagnostic blood specimens for 56 NHL cases and 190
      controls matched for age, sex, race, specimen type, cohort, and CD4 T-cell count
      were tested for the endotoxin lipopolysaccharide (LPS), antiendotoxin core
      antibody (EndoCab), LPS-binding protein (LBP), and soluble CD14 (sCD14). RESULTS:
      Elevated levels of sCD14 were associated with significantly increased NHL risk
      [odds ratio (OR) 2.72 (95% confidence interval [95% CI] 1.29-5.76)]. In subgroup
      analyses, elevated LPS levels were also associated with significantly increased
      NHL risk [OR 3.24 (95% CI 1.10-9.53)]. EndoCab and LBP levels were not associated
      with NHL risk. CONCLUSION: The association of sCD14 and LPS with NHL risk
      supports an etiologic role for gut microbial translocation in lymphomagenesis
      among HIV-infected individuals. Additional studies with larger sample sizes are
      needed to confirm these observations.

PMID- 23169328
TI  - Elevations in D-dimer and C-reactive protein are associated with the development
      of osteonecrosis of the hip in HIV-infected adults.
AB  - BACKGROUND: A high incidence of nontraumatic osteonecrosis has been reported in
      HIV-infected patients. We investigated the levels of D-dimer and C-reactive
      protein (CRP) in a cohort of HIV-infected adults with and without osteonecrosis
      of the femoral head. METHODS: Forty-three HIV-infected patients with
      osteonecrosis of the femoral head and a comparison group of 50 HIV-infected
      patients with negative MRI of the hips and for whom serial plasma samples were
      available were included. D-dimer and CRP levels were measured prior to and at the
      time of diagnosis for osteonecrosis patients, at the time of negative MRI of the
      hips for controls, and at least 6 months later for both groups. RESULTS:
      Biomarker levels were elevated at the time of diagnosis in the osteonecrosis
      cohort compared with controls. Median D-dimer value was 0.32 MUg/ml in the
      osteonecrosis group compared with less than 0.22 MUg/ml in the control group (P =
      0.016). For CRP, the corresponding values were 2.52 mg/l and 1.23 mg/l (P =
      0.003). Postdiagnosis, D-dimer and CRP levels were also elevated in the
      osteonecrosis patients compared with controls. Linear regression demonstrated a
      rise in D-dimer levels from prediagnosis to diagnosis in the osteonecrosis
      patients whereas CRP levels did not change significantly over time. CONCLUSION:
      Compared to controls, patients who developed osteonecrosis had elevated levels of
      D-dimer and CRP at diagnosis. D-dimer levels increased whereas CRP levels did not
      change significantly from prediagnosis to diagnosis. These data suggest that
      patients with higher levels of inflammation are at an increased risk of
      osteonecrosis.

PMID- 23169329
TI  - The pharmacokinetics, safety and efficacy of tenofovir and emtricitabine in HIV-1
      infected pregnant women.
AB  - OBJECTIVE: To describe the pharmacokinetics of tenofovir and emtricitabine in the
      third trimester of pregnant HIV-infected women and at postpartum. DESIGN: A
      nonrandomized, open-label, multicentre phase IV study in HIV-infected pregnant
      women recruited from HIV treatment centres in Europe. METHODS: HIV-infected
      pregnant women treated with the nucleotide/nucleoside analogue reverse
      transcriptase inhibitors (NRTIs) tenofovir disoproxil fumarate (TDF 300 mg;
      equivalent to 245 mg tenofovir disoproxil) and/or emtricitabine (FTC 200 mg) were
      included in the study. Twenty-four-hour pharmacokinetic curves were recorded in
      the third trimester (preferably week 33) and postpartum (preferably week 4-6).
      Collection of a cord blood sample and maternal sample at delivery was optional.
      Pharmacokinetic parameters were calculated using WinNonlin software version 5.3.
      Statistical analysis was conducted using SPSS version 16.0. RESULTS: Thirty-four
      women were included in the analysis. Geometric mean ratios of third trimester vs.
      postpartum [90% confidence interval (CI)] were 0.77 (0.71-0.83) for TDF area
      under the curve (AUC0-24 h); 0.81 (0.68-0.96) for TDF Cmax and 0.79 (0.70-0.90)
      for TDF C24 h and 0.75 (0.68-0.82) for FTC AUC0-24 h; and 0.87 (0.77-0.99) for
      FTC Cmax and 0.77 (0.52-1.12) for FTC C24 h. The viral load close to delivery was
      less than 200  copies/ml in all but one patient, the average gestational age at
      delivery was 38 weeks. All children were tested HIV-negative and no congenital
      abnormalities were reported. CONCLUSION: Although pharmacokinetic exposure of the
      NRTIs TDF and FTC during pregnancy is approximately 25% lower, this was not
      associated with virological failure in this study and did not result in mother-to
      child transmission.

PMID- 23169330
TI  - Evidence of an explosive epidemic of HIV infection in a cohort of men who have
      sex with men in Thailand.
AB  - OBJECTIVE: To assess HIV-prevalence, incidence and risk factors in a cohort of
      men who have sex with men (MSM) in Bangkok. DESIGN: : Cohort study with 4-monthly
      follow-up visits conducted between April 2006 and July 2012 at a dedicated study
      clinic in a central Bangkok hospital. Participants were 1744 homosexually active
      Thai men, at least 18 years old and residents of Bangkok. METHODS: Men were
      tested for HIV-infection at every study visit and for sexually transmitted
      infections at baseline. Demographic and behavioural data were collected by audio
      computer-assisted self-interview. Logistic regression analysis was used to
      evaluate risk factors for HIV-prevalence and Cox proportional hazard analysis to
      evaluate risk factors for HIV-incidence. RESULTS: Baseline HIV-prevalence was
      21.3% (n = 372) and 60 months cumulative HIV-incidence was 23.9% (n = 222).
      Overall HIV-incidence density was 5.9 per 100 person-years. Multivariate risk
      factors for HIV-prevalence were older age, secondary/vocational education (vs.
      university or higher), employed or unemployed (vs. studying), nitrate inhalation,
      drug use for sexual pleasure, receptive anal intercourse, history of sexual
      coercion, no prior HIV-testing, and anti-HSV-1 and 2 and Treponema pallidum
      positivity at baseline. Multivariate risk factors for HIV-incidence were younger
      age, living alone or with roommate (vs. with a partner or family), drug use for
      sexual pleasure, inconsistent condom use, receptive anal intercourse, group sex,
      and anti-HSV-1 and 2 and T. pallidum positivity at baseline. Having no anal
      intercourse partners was inversely associated with HIV-incidence. CONCLUSION: The
      high HIV prevalence and incidence in this cohort of Bangkok MSM documents an
      explosive epidemic. Additional preventive interventions for MSM are urgently
      needed.

PMID- 23169331
TI  - Frequency of stavudine substitution due to toxicity in children receiving
      antiretroviral treatment in sub-Saharan Africa.
AB  - INTRODUCTION: Stavudine is a commonly used drug in paediatric antiretroviral
      treatment (ART) regimens. Due to toxicity concerns, however, the drug abacavir
      has replaced stavudine in first-line paediatric regimens in many countries. We
      describe the frequency of stavudine toxicity in children receiving ART at a
      treatment clinic in Soweto, South Africa. METHODS: Data on patient
      characteristics and outcomes of ART were collected from a cohort of 2222 HIV
      infected children initiating ART between 2004 and 2008 when stavudine-containing
      regimens were routinely recommended. At several time-points after treatment
      initiation, we estimate the proportion of children where an attending clinician
      discontinued stavudine due to lipodystrophy, pancreatitis, lactic acidosis or
      peripheral neuropathy. Factors associated with stavudine-related toxicities were
      identified. RESULTS: At ART initiation, most children had advanced disease. The
      majority initiated an efavirenz/lamivudine/stavudine regimen (n = 1422), and 76%
      of children remained on their initial ART regimen after a median 19.9 months of
      ART. Replacement of stavudine due to drug toxicity occurred at a rate of 28.8 per
      1000 child years on treatment (95% confidence interval = 23.6-35.2). Rates of
      toxicity increased with treatment duration (in their first year of ART stavudine
      was replaced in 0.5% of children, but after 3 years stavudine had been changed to
      abacavir in 12.6% of children). Toxicity was more common in older children and in
      girls. Lipodystrophy accounted for 87 of 96 toxic events. CONCLUSION: Stavudine
      associated toxicity resulting in single-drug substitution was uncommon in this
      cohort, though its frequency increased steadily with ART duration, especially
      with lipodystrophy. Where drug options are limited, stavudine remains a
      relatively well tolerated and effective option for children.

PMID- 23169333
TI  - The cost-effectiveness of expanded HIV screening in the United States.
AB  - OBJECTIVE: The current Centers of Disease Control and Prevention (CDC) guidelines
      from 2006 recommend a one-time test for low-risk individuals and annual testing
      for those at high risk. These guidelines may not be aggressive enough, even for
      those at low risk of infection, due to the earlier initiation of HAART and a
      movement towards a test-and-treat environment. We evaluated the optimal testing
      frequencies for various risk groups in comparison to the CDC recommendations.
      METHODS: We build a deterministic mathematical model optimizing the tradeoff
      between the societal cost of testing and the benefits over a patient's lifetime
      of earlier diagnosis. RESULTS: Under a test-and-treat scenario with immediate
      initiation of HAART, the optimal testing frequency is every 2.4 years for low
      risk (0.01% annual incidence) individuals; every 9 months for moderate risk (0.1%
      incidence) individuals; and every 3 months for high-risk (1.0% incidence)
      individuals. The incremental cost-effectiveness of the optimal policy is $ 36
      ,342/quality-adjusted life-years (QALY) for low-risk individuals and $ 45
      ,074/QALY for high-risk individuals compared with 20-year and annual testing,
      respectively. CONCLUSION: The current CDC guidelines for HIV testing are too
      conservative, and more frequent testing is cost-effective for all risk groups.

PMID- 23169332
TI  - Improved employment and education outcomes in households of HIV-infected adults
      with high CD4 cell counts:  evidence from a community health campaign in Uganda.
AB  - BACKGROUND: There is limited evidence on the association between socioeconomic
      outcomes and CD4 counts in populations that include HIV-infected adults who have
      high CD4 counts or have not been diagnosed. We examined this association among
      adults in a rural Ugandan parish. METHODS: A community health campaign offering
      diagnostic and treatment services for HIV and other diseases was conducted with
      Ministry of Health support. Data on campaign participants' education and
      employment were collected and a detailed household socioeconomic survey was
      conducted among a subset of participants. Regression analyses were used to assess
      relationships between CD4 count and employment and education outcomes. RESULTS: A
      total of 2323 adults (74% of the community) participated in the campaign; 179 of
      2282 (7.8%) tested HIV-positive and 46% were newly diagnosed. Among HIV-infected
      adults not on antiretroviral therapy (ART), those with CD4 at least 500 worked
      6.9 more days/month (P < 0.01; 39% more) and 2.5 more h per day (P < 0.05, 44%
      more) than those with CD4 less than 200. These effects were not significantly
      different from the effects for those with CD4 350-499. Children aged 6-11 years
      in households of adults with CD4 at least 350 did not have significantly
      different school enrollment rates than children in households of adults with CD4
      less than 350, but differences were larger among children aged 12-18 years.
      CONCLUSION: Outcomes of HIV-infected adults with CD4 at least 350 were better
      than those of adults with CD4 less than 200 and resembled those of HIV-uninfected
      adults. The results suggest that early ART initiation may generate economic
      benefits by preventing a decline in socioeconomic status, but further research is
      needed to determine the CD4 threshold at which these benefits would be largest.

PMID- 23169334
TI  - Smaller sample sizes for phase II trials based on exact tests with actual error
      rates by trading-off their nominal levels of significance and power.
AB  - BACKGROUND: Sample sizes for single-stage phase II clinical trials in the
      literature are often based on exact (binomial) tests with levels of significance
      (alpha (alpha) <5% and power >80%). This is because there is not always a sample
      size where alpha and power are exactly equal to 5% and 80%, respectively.
      Consequently, the opportunity to trade-off small amounts of alpha and power for
      savings in sample sizes may be lost. METHODS: Sample-size tables are presented
      for single-stage phase II trials based on exact tests with actual levels of
      significance and power. Trade-off in small amounts of alpha and power allows the
      researcher to select from several possible designs with potentially smaller
      sample sizes compared with existing approaches. We provide SAS macro coding and
      an R function, which for a given treatment difference, allow researchers to
      examine all possible sample sizes for specified differences are provided.
      RESULTS: In a single-arm study with P(0) (standard treatment)=10% and P(1) (new
      treatment)=20%, and specified alpha=5% and power=80%, the A'Hern approach yields
      n=78 (exact alpha=4.53%, power=80.81%). However, by relaxing alpha to 5.67% and
      power to 77.7%, a sample size of 65 can be used (a saving of 13 patients).
      INTERPRETATION: The approach we describe is especially useful for trials in rare
      disorders, or for proof-of-concept studies, where it is important to minimise the
      trial duration and financial costs, particularly in single-arm cancer trials
      commonly associated with expensive treatment options.

PMID- 23169335
TI  - Risk stratification of pT1-3N0 patients after radical cystectomy for adjuvant
      chemotherapy counselling.
AB  - BACKGROUND: In pT1-T3N0 urothelial carcinoma of the bladder (UCB) patients, multi
      modal therapy is inconsistently recommended. The aim of the study was to develop
      a prognostic tool to help decision-making regarding adjuvant therapy. METHODS: We
      included 2145 patients with pT1-3N0 UCB after radical cystectomy (RC), naive of
      neoadjuvant or adjuvant therapy. The cohort was randomly split into development
      cohort based on the US patients (n=1067) and validation cohort based on the
      Europe patients (n=1078). Predictive accuracy was quantified using the
      concordance index. RESULTS: With a median follow-up of 45 months, 5-year
      recurrence-free and cancer-specific survival estimates were 68% and 73%,
      respectively. pT-stage, ge, lymphovascular invasion, and positive margin were
      significantly associated with both disease recurrence and cancer-specific
      mortality (P-values <= 0.005). The accuracies of the multivariable models at 2,
      5, and 7 years for predicting disease recurrence were 67.4%, 65%, and 64.4%,
      respectively. Accuracies at 2, 5, and 7 years for predicting cancer-specific
      mortality were 69.3%, 66.4%, and 65.5%, respectively. We developed competing
      risk, conditional probability nomograms. External validation revealed minor
      overestimation. CONCLUSION: Despite RC, a significant number of patients with pT1
      3N0 UCB experience disease recurrence and ultimately die of UCB. We developed and
      externally validated competing-risk, conditional probability post-RC nomograms
      for prediction of disease recurrence and cancer-specific mortality.

PMID- 23169336
TI  - Sperm counts and endocrinological markers of spermatogenesis in long-term
      survivors of testicular cancer.
AB  - BACKGROUND: The objective of this study was to assess markers of spermatogenesis
      in long-term survivors of testicular cancer (TC) according to treatment, and to
      explore correlations between the markers and associations with achieved paternity
      following TC treatment. METHODS: In 1191 TC survivors diagnosed between 1980 and
      1994, serum-follicle stimulating hormone (s-FSH; n=1191), s-inhibin B (n=441),
      and sperm counts (millions per ml; n=342) were analysed in a national follow-up
      study in 1998-2002. Paternity was assessed by a questionnaire. RESULTS: At median
      11 years follow-up, 44% had oligo- (<15 millions per ml; 29%) or azoospermia
      (15%). Sperm counts and s-inhibin B were significantly lower and s-FSH was higher
      after chemotherapy, but not after radiotherapy (RT), when compared with surgery
      only. All measures were significantly more abnormal following high doses of
      chemotherapy (cisplatin (Cis)>850 mg, absolute cumulative dose) compared with
      lower doses (Cis <= 850 mg). Sperm counts were moderately correlated with s-FSH (
      0.500), s-inhibin B (0.455), and s-inhibin B : FSH ratio (-0.524; all P<0.001).
      All markers differed significantly between those who had achieved post-treatment
      fatherhood and those with unsuccessful attempts. CONCLUSION: The RT had no long
      term effects on the assessed markers of spermatogenesis, whereas chemotherapy
      had. At present, the routine evaluation of s-inhibin B adds little in the initial
      fertility evaluation of TC survivors.

PMID- 23169337
TI  - Differential downregulation of telomerase activity by bortezomib in multiple
      myeloma cells-multiple regulatory pathways in vitro and ex vivo.
AB  - BACKGROUND: The importance of telomerase in multiple myeloma (MM) is well
      established; however, its response to bortezomib has not been addressed. METHODS:
      The effect of bortezomib on telomerase activity and cell proliferation was
      evaluated in four MM cell lines and in myeloma cells obtained from eight
      patients. The mechanism of telomerase regulation on epigenetic, transcriptional,
      and post-translational levels was further assessed in two selected cell lines:
      ARP-1 and CAG. Clinical data were correlated with the laboratory findings.
      RESULTS: Bortezomib downregulated telomerase activity and decreased proliferation
      in all cell lines and cells obtained from patients, albeit in two different
      patterns of kinetics. ARP-1 cells demonstrated higher and earlier sensitivity
      than CAG cells due to differential phosphorylation of hTERT by PKCalpha.
      Methylation of hTERT promoter was not affected. Transcription of hTERT was
      similarly inhibited in both lines by decreased binding of SP-1 and not of C-Myc
      and NFkappaB. The ex vivo results confirmed the in vitro findings and suggested
      existence of clinical relevance. CONCLUSION: Bortezomib downregulates telomerase
      activity in MM cells both transcriptionally and post-translationally. MM cells,
      both in vitro and in patients, exhibit different sensitivity to the drug due to
      different post-translational response. The effect of bortezomib on telomerase
      activity may correlate with resistance to bortezomib in patients, suggesting its
      potential utility as a pre-treatment assessment.

PMID- 23169338
TI  - Anti-tumour activity of two novel compounds in cisplatin-resistant testicular
      germ cell cancer.
AB  - BACKGROUND: Resistance to cisplatin-based chemotherapy is associated with poor
      prognosis in testicular germ cell cancer, emphasising the need for new
      therapeutic approaches. In this respect, the therapeutic concept of anti
      angiogenesis is of particular interest. In a previous study, we presented two
      novel anti-angiogenic compounds, HP-2 and HP-14, blocking the tyrosine kinase
      activity of angiogenic growth factor receptors, such as vascular endothelial
      growth factor receptor-2 (VEGFR-2), and related signalling pathways in testicular
      cancer. In this study, we investigated the efficacy of these new compounds in
      platinum-resistant testicular germ cell tumours (TGCTs), in vitro and in vivo.
      METHODS AND RESULTS: Drug-induced changes in cell proliferation of the cisplatin
      sensitive TGCT cell line 2102EP and its cisplatin-resistant counterpart 2102EP-R,
      both expressing the VEGFR-2, were evaluated by crystal violet staining. Both
      compounds inhibited the growth of cisplatin-resistant TGCT cells in a dose
      dependent manner. In combination experiments with cisplatin, HP-14 revealed
      additive growth-inhibitory effects in TGCT cells, irrespective of the level of
      cisplatin resistance. Anti-angiogenic effects of HP compounds were confirmed by
      tube formation assays with freshly isolated human umbilical vein endothelial
      cells. Using TGCT cells inoculated onto the chorioallantoic membrane of
      fertilised chicken eggs (chicken chorioallantoic membrane assay), the anti
      angiogenic and anti-proliferative potency of the novel compounds was also
      demonstrated in vivo. Gene expression profiling revealed changes in the
      expression pattern of genes related to DNA damage detection and repair, as well
      as in chaperone function after treatment with both cisplatin and HP-14, alone or
      in combination. This suggests that HP-14 can revert the lost effectiveness of
      cisplatin in the resistant cells by altering the expression of critical genes.
      CONCLUSION: The novel compound HP-14 effectively inhibits the growth of cisplatin
      resistant TGCT cells and suppresses tumour angiogenesis. Thus, HP-14 may be an
      interesting new agent that should be further explored for TGCT treatment,
      especially in TGCTs that are resistant to cisplatin.

PMID- 23169339
TI  - VEGF directly suppresses activation of T cells from ascites secondary to ovarian
      cancer via VEGF receptor type 2.
AB  - BACKGROUND: Vascular endothelial growth factor action in tumour angiogenesis is
      well characterised; nevertheless, it functions as a key element in the promotion
      of the immune system's evasion by tumours. We sought to investigate the possible
      direct effect of VEGF on T-cell activation and through which type of VEGF
      receptor it exerts this effect on cells isolated from ovarian cancer patients'
      ascites. METHODS: T cells isolated from the ascites of ovarian cancer patients
      were cultured with anti-CD3 and IL-2, with or without VEGF for 14 days and the
      number of viable T cells was counted. Cytotoxic activity of cultured T cells and
      expression of VEGF receptor-2 (VEGFR-2), was assayed. RESULTS: The addition of
      VEGF in cultures significantly reduced the number and proliferation rate of T
      cells in a dose-dependent manner and CD3(+) T cells expressed VEGFR-2 on their
      surface upon activation. Experiments with specific anti-VEGFR-2 antibodies
      revealed that the direct suppressive effect of VEGF on T-cell proliferation is
      mediated by VEGFR-2. We also showed that VEGF significantly reduced the cytotoxic
      activity of T cells. CONCLUSION: Our study showed that ascites-derived T cells
      secrete VEGF and express VEGFR-2 upon activation. Vascular endothelial growth
      factor directly suppresses T-cell activation via VEGFR-2.

PMID- 23169340
TI  - Serum apolipoprotein C-II is prognostic for survival after pancreatic resection
      for adenocarcinoma.
AB  - BACKGROUND: Pancreaticoduodenectomy remains a major undertaking. A preoperative
      blood test, which could confidently predict the benefits of surgery would improve
      the selection of pancreatic cancer patients for surgery. This study aimed to
      identify protein biomarkers prognostic for long-term survival and to validate
      them with clinico-pathological information. METHODS: Serum from 40 preoperative
      patients was used to train for predictive biomarkers using surface-enhanced laser
      desorption/ionisation time-of-flight mass spectrometry (SELDI), and the results
      were verified on 21 independent samples. Two predictive proteins were identified
      by tryptic peptide mass fingerprinting and sequencing, and validated on serum
      from another 57 patients by enzyme-linked immunosorbent assay (ELISA). The
      influence of these proteins on growth and invasion of two cancer cell lines was
      tested in-vitro. RESULTS: The SELDI panel of m/z 3700, 8222 and 11 522 peaks
      predicted <12 months' survival (ROC AUC: 0.79, 0.64-0.90; P<0.039). When CA19-9
      was added, the ROC AUC increased to 0.95 (0.84-0.99; P<0.0001). The six subjects
      in the verification group who died within 12 months were correctly classified.
      The m/z 8222 and 11 522 proteins were identified as Serum ApoC-II and SAA-1,
      respectively. In the validation samples, ELISA results confirmed that ApoC-II was
      predictive of survival (Kaplan-Meier P<0.009), but not SAA-I. ApoC-II, CA19-9 and
      major-vessel involvement independently predicted survival. ApoC-II and SAA-1
      increased cell growth and invasion of both cancer cell lines. CONCLUSION: Serum
      ApoC-II, CA19-9 and major-vessel invasion independently predict survival and
      improves selection of patients for pancreaticoduodenectomy.

PMID- 23169341
TI  - Nerve allografts supplemented with schwann cells overexpressing glial-cell-line
      derived neurotrophic factor.
AB  - INTRODUCTION: We sought to determine whether supplementation of acellular nerve
      allografts (ANAs) with Schwann cells overexpressing GDNF (G-SCs) would enhance
      functional recovery after peripheral nerve injury. METHODS: SCs expanded in vitro
      were infected with a lentiviral vector to induce GDNF overexpression. Wild-type
      SCs (WT-SCs) and G-SCs were seeded into ANAs used to repair a 14-mm nerve gap
      defect. Animals were harvested after 6 and 12 weeks for histomorphometric and
      muscle force analysis. RESULTS: At 6 weeks, histomorphometry revealed that ANAs
      supplemented with G-SCs promoted similar regeneration compared with isograft at
      midgraft. However, G-SCs failed to promote regeneration into the distal stump. At
      12 weeks, ANAs with G-SCs had lower maximum and specific force production
      compared with controls. CONCLUSIONS: The combined results suggest that consistent
      overexpression of GDNF by G-SCs trapped axons in the graft and prevented
      functional regeneration.

PMID- 23169342
TI  - Digestive efficiency mediated by serum calcium predicts bone mineral density in
      the common marmoset (Callithrix jacchus).
AB  - Two health problems have plagued captive common marmoset (Callithrix jacchus)
      colonies for nearly as long as those colonies have existed: marmoset wasting
      syndrome and metabolic bone disease. While marmoset wasting syndrome is
      explicitly linked to nutrient malabsorption, we propose metabolic bone disease is
      also linked to nutrient malabsorption, although indirectly. If animals experience
      negative nutrient balance chronically, critical nutrients may be taken from
      mineral stores such as the skeleton, thus leaving those stores depleted. We
      indirectly tested this prediction through an initial investigation of digestive
      efficiency, as measured by apparent energy digestibility, and serum parameters
      known to play a part in metabolic bone mineral density of captive common marmoset
      monkeys. In our initial study on 12 clinically healthy animals, we found a wide
      range of digestive efficiencies, and subjects with lower digestive efficiency had
      lower serum vitamin D despite having higher food intakes. A second experiment on
      23 subjects including several with suspected bone disease was undertaken to
      measure digestive and serum parameters, with the addition of a measure of bone
      mineral density by dual-energy X-ray absorptiometry (DEXA). Bone mineral density
      was positively associated with apparent digestibility of energy, vitamin D, and
      serum calcium. Further, digestive efficiency was found to predict bone mineral
      density when mediated by serum calcium. These data indicate that a poor ability
      to digest and absorb nutrients leads to calcium and vitamin D insufficiency.
      Vitamin D absorption may be particularly critical for indoor-housed animals, as
      opposed to animals in a more natural setting, because vitamin D that would
      otherwise be synthesized via exposure to sunlight must be absorbed from their
      diet. If malabsorption persists, metabolic bone disease is a possible consequence
      in common marmosets. These findings support our hypothesis that both wasting
      syndrome and metabolic bone disease in captive common marmosets are consequences
      of inefficient nutrient absorption.

PMID- 23169343
TI  - Functional expression of a Bombyx mori cocoonase: potential application for silk
      degumming.
AB  - Cocoon, a shelter for larva development to silk moth, contains the fibrous
      protein fibroin, which is coated by the globular protein sericin. Emergence of
      the silk moth requires the action of cocoonase, a protease secreted by the pupa.
      The full-length prococoonase cDNA, with 780 bp open reading frame encoding 260
      amino acids, was cloned by reverse transcription from total RNA of the head of 6
      day-old Thai-silk Bombyx mori pupa. Only the gene fragment lacking the propeptide
      encoding sequence was successfully expressed in Pichia pastoris, yielding an
      extracellularly active cocoonase. The recombinant cocoonase was purified to
      homogeneity by 80% ammonium-sulfate fractionation and CM-Sepharose
      chromatography, and its internal peptide sequences were analyzed by nano liquid
      chromatography-mass spectrometry/mass spectrometry. This monomeric protein has
      native molecular weight of 26 kDa by gel exclusion analysis and 25 kDa subunit
      size by sodium dodecyl sulphate-polyacrylamide gel electrophoresis. The enzyme
      hydrolyses sericin but does not hydrolyse fibroin, as shown by radial diffusion
      on thin-layer enzyme assay (RD-TEA). Scanning electron microscopy showed that
      purified recombinant cocoonase could remove sericin from natural silk completely
      in 24 h, without damaging fibroin, using only 1 immobilized sericin unit (ISU) of
      enzyme as determined by RD-TEA. Natural cocoonase isolated from B. mori pupa
      could also digest sericin effectively, but required more enzymes (2 ISU) and
      longer time (48 h). In comparison, a commercial enzyme, alcalase, with the same
      activity not only showed less complete digestion of sericin but also caused
      damage of fibroin. These results suggest that recombinant B. mori cocoonase is
      potentially useful for silk degumming.

PMID- 23169344
TI  - YB-1 immunization combined with regulatory T-cell depletion induces specific T
      cell responses that protect against neuroblastoma in the early stage.
AB  - Neuroblastoma is the most common extracranial solid cancer in childhood and the
      most common cancer in infancy. Currently, no effective clinical treatments are
      available for advanced neuroblastoma. In a previous study, we screened Y Box
      protein 1 (YB-1) as a potential neuroblastoma-associated antigen from sera of
      AGN2a-immunized mice by serological analysis of recombinant cDNA expression
      libraries technique. The aim of this study is to explore if YB-1 immunization in
      the context of Treg depletion could induce protective immune response against the
      neuroblastoma in mice. YB-1 was expressed and purified by pET-15b prokaryotic
      expression system. It was demonstrated that anti-YB-1 CD8(+) T-cell responses
      could be induced by AGN2a immunization, and the strongest CD8(+) T-cell responses
      against AGN2a were induced by YB-1-immunized mice in the context of Treg
      depletion compared with YB-1 only immunization group and control group.
      Importantly, the survival rate of mice treated with YB-1 immunization combined
      with Treg depletion was 80% when challenged by 1 * 10(4) AGN2a cells,
      significantly higher than that of mice immunized with YB-1 alone (P < 0.01).
      Furthermore, T-cell adoptive therapy showed that the neuroblastoma growth was
      inhibited when T cells or splenic cells from YB-1-immunized mice with Treg
      depletion were transferred to AGN2a bearing mice. Both CD4(+) and CD8(+) T cells
      were involved in the anti-neuroblastoma responses induced by YB-1 immunization
      combined with Treg depletion. These results indicated that YB-1 immunization
      combined with Treg depletion could induce specific T-cell responses against
      neuroblastoma and could be a potential strategy for the prevention and treatment
      of neuroblastoma in the early stage.

PMID- 23169345
TI  - Effect of antimicrobial preservatives on partial protein unfolding and
      aggregation.
AB  - One-third of protein formulations are multi-dose. These require antimicrobial
      preservatives (APs); however, some APs have been shown to cause protein
      aggregation. Our previous work on a model protein cytochrome c indicated that
      partial protein unfolding, rather than complete unfolding, triggers aggregation.
      Here, we examined the relative strength of five commonly used APs on such
      unfolding and aggregation, and explored whether stabilizing the aggregation 'hot
      spot' reduces such aggregation. All APs induced protein aggregation in the order
      m-cresol > phenol > benzyl alcohol > phenoxyethanol > chlorobutanol. All these
      enhanced the partial protein unfolding that includes a local region which was
      predicted to be the aggregation 'hot-spot'. The extent of destabilization
      correlated with the extent of aggregation. Further, we show that stabilizing the
      'hot-spot' reduces aggregation induced by all five APs. These results indicate
      that m-cresol causes the most protein aggregation, whereas chlorobutanol causes
      the least protein aggregation. The same protein region acts as the 'hot-spot' for
      aggregation induced by different APs, implying that developing strategies to
      prevent protein aggregation induced by one AP will also work for others.

PMID- 23169346
TI  - Glucocorticoid receptor and FKBP5 expression is altered following exposure to
      chronic stress: modulation by antidepressant treatment.
AB  - Major depression is thought to originate from the interaction between
      susceptibility genes and adverse environmental events, in particular stress. The
      hypothalamus-pituitary-adrenal (HPA) axis is the major system involved in stress
      response and its dysregulation is an important element in the pathogenesis of
      depression. The stress response is therefore finely tuned through a series of
      mechanisms that control the trafficking of glucocorticoid receptors (GRs) to the
      nucleus, including binding to the chaperone protein FKBP5 and receptor
      phosphorylation, suggesting that these elements may also be affected under
      pathologic conditions. On these bases, we investigated FKBP5 and GR expression
      and phosphorylation in the hippocampus (ventral and dorsal) and in the prefrontal
      cortex of rats exposed to chronic mild stress (CMS) and we analyzed the effect of
      a concomitant antidepressant treatment. We found that animals exposed to CMS show
      increased expression of FKBP5 as well as enhanced cytoplasmic levels of GR,
      primarily in ventral hippocampus and prefrontal cortex. Chronic treatment with
      the antidepressant duloxetine is able to normalize such alterations, mainly in
      the prefrontal cortex. Moreover, we demonstrate that CMS-induced alterations of
      GR trafficking and transcription may be sustained by changes in receptor
      phosphorylation, which are also modulated by pharmacological intervention. In
      summary, while GR-related changes after CMS might be relevant for the depressive
      phenotype, the ability of antidepressant treatment to correct some of these
      alterations may contribute to the normalization of HPA axis dysfunctions
      associated with stress-related disorders.

PMID- 23169347
TI  - The synaptic adhesion molecule SynCAM 1 contributes to cocaine effects on synapse
      structure and psychostimulant behavior.
AB  - Drugs of abuse have acute and persistent effects on synapse structure and
      addiction-related behaviors. Trans-synaptic interactions can control synapse
      development, and synaptic cell adhesion molecule (SynCAM) proteins (also named
      nectin-like molecules) are immunoglobulin adhesion proteins that span the
      synaptic cleft and induce excitatory synapses. Our studies now reveal that the
      loss of SynCAM 1 in knockout (KO) mice reduces excitatory synapse number in
      nucleus accumbens (NAc). SynCAM 1 additionally contributes to the structural
      remodeling of NAc synapses in response to the psychostimulant cocaine.
      Specifically, we find that cocaine administration increases the density of stubby
      spines on medium spiny neurons in NAc, and that maintaining this increase
      requires SynCAM 1. Furthermore, mushroom-type spines on these neurons are
      structurally more plastic when SynCAM 1 is absent, and challenging drug-withdrawn
      mice with cocaine shortens these spines in SynCAM 1 KO mice. These effects are
      correlated with changes on the behavioral level, where SynCAM 1 contributes to
      the psychostimulant effects of cocaine as measured after acute and repeated
      administration, and in drug-withdrawn mice. Together, our results provide
      evidence that the loss of a synapse-organizing adhesion molecule can modulate
      cocaine effects on spine structures in NAc and increases vulnerability to the
      behavioral actions of cocaine. SynCAM-dependent pathways may therefore represent
      novel points of therapeutic intervention after exposure to drugs of abuse.

PMID- 23169348
TI  - The volitional nature of nicotine exposure alters anandamide and
      oleoylethanolamide levels in the ventral tegmental area.
AB  - Cannabinoid-1 receptors (CB(1)) have an important role in nicotine reward and
      their function is disrupted by chronic nicotine exposure, suggesting nicotine
      induced alterations in endocannabinoid (eCB) signaling. However, the effects of
      nicotine on brain eCB levels have not been rigorously evaluated. Volitional
      intake of nicotine produces physiological and behavioral effects distinct from
      forced drug administration, although the mechanisms underlying these effects are
      not known. This study compared the effects of volitional nicotine self
      administration (SA) and forced nicotine exposure (yoked administration (YA)) on
      levels of eCBs and related neuroactive lipids in the ventral tegmental area (VTA)
      and other brain regions. Brain lipid levels were indexed both by in vivo
      microdialysis in the VTA and lipid extractions from brain tissues. Nicotine SA,
      but not YA, reduced baseline VTA dialysate oleoylethanolamide (OEA) levels
      relative to nicotine-naive controls, and increased anandamide (AEA) release
      during nicotine intake. In contrast, all nicotine exposure paradigms increased
      VTA dialysate 2-arachidonoyl glycerol (2-AG) levels. Thus, nicotine
      differentially modulates brain lipid (2-AG, AEA, and OEA) signaling, and these
      modulations are influenced by the volitional nature of the drug exposure.
      Corresponding bulk tissue analysis failed to identify these lipid changes.
      Nicotine exposure had no effect on fatty acid amide hydrolase activity in the
      VTA, suggesting that changes in AEA and OEA signaling result from alterations in
      their nicotine-induced biosynthesis. Both CB(1) (by AEA and 2-AG) and non-CB(1)
      (by OEA) targets can alter the excitability and activity of the dopaminergic
      neurons in the VTA. Collectively, these findings implicate disrupted lipid
      signaling in the motivational effects of nicotine.

PMID- 23169349
TI  - Involvement of protein degradation by the ubiquitin proteasome system in opiate
      addictive behaviors.
AB  - Plastic changes in the nucleus accumbens (NAcc), a structure occupying a key
      position in the neural circuitry related to motivation, are among the critical
      cellular processes responsible for drug addiction. During the last decade, it has
      been shown that memory formation and related neuronal plasticity may rely not
      only on protein synthesis but also on protein degradation by the ubiquitin
      proteasome system (UPS). In this study, we assess the role of protein degradation
      in the NAcc in opiate-related behaviors. For this purpose, we coupled behavioral
      experiments to intra-accumbens injections of lactacystin, an inhibitor of the
      UPS. We show that protein degradation in the NAcc is mandatory for a full range
      of animal models of opiate addiction including morphine locomotor sensitization,
      morphine conditioned place preference, intra-ventral tegmental area morphine self
      administration and intra-venous heroin self-administration but not for
      discrimination learning rewarded by highly palatable food. This study provides
      the first evidence of a specific role of protein degradation by the UPS in
      addiction.

PMID- 23169350
TI  - Sharing a diagnosis of HPV-related head and neck cancer: the emotions, the
      confusion, and what patients want to know.
AB  - BACKGROUND: Oropharyngeal cancers are increasingly associated with human
      papillomavirus (HPV). Little is known about the experience of patients receiving
      this diagnosis. METHODS: Semistructured interviews were conducted with ten
      survivors of HPV-related oropharyngeal cancer. The interviews were transcribed,
      and recurring themes were identified. RESULTS: Physicians were a trusted source
      of information regarding HPV. Framing the diagnosis in terms of prognosis
      resonated with patients. The uncertainty about transmission, latency, and
      communicability colored the dialogue about HPV. Despite some understanding of
      prevalence and transmission, patients worried about their partner's risk.
      Patients sought information about HPV on the Internet, but it was not easily
      navigable. Emotional reactions to the diagnosis remained mostly cancer-centric
      rather than HPV-centric. A patient-education handout was developed in response to
      patient questions. CONCLUSIONS: Additional educational resources explaining the
      facts about HPV in HNSCC in a consistent way including content of highest
      priority to patients may improve understanding of HPV.

PMID- 23169351
TI  - ORD work and initiative group ("optimising results in dialysis").

PMID- 23169352
TI  - Improving strategy to reduce kidney transplant waiting: type III non-beating
      heart donors.

PMID- 23169353
TI  - Encapsulating peritoneal sclerosis in peritoneal dialysis. a review and European
      initiative for approaching a serious and rare disease.
AB  - Encapsulating peritoneal sclerosis (EPS) represents a rare complication in
      peritoneal dialysis (PD) with high mortality. It is characterised by diffuse
      peritoneal membrane fibrosis, which develops into encapsulation and manifests as
      clinical signs and symptoms of intestinal obstruction. Its incidence varies from
      0.7%to 3.3%. The most significant risk factor in its development is exposure time
      to PD solutions, although young age and peritonitis episodes can also contribute.
      Its aetiopathogeny has not been clearly explained and it is thought that a second
      hit like peritonitis, hemoperitoneum, surgery, genetic predisposition, etc on an
      already damaged peritoneal membrane, could also trigger the development of EPS.
      Some cases appear after transfer to haemodialysis or after transplant. In these
      cases, the use of calcineurin inhibitors is believed to be related. The presence
      of clinical symptoms and signs of intestinal obstruction, along with compatible
      radiological and/or anatomical findings could also confirm the diagnosis. At
      present there are no clinical or biochemical markers capable of predicting its
      onset. Therapeutic management comprises the use of immunosuppressors like
      steroids and tamoxifen, nutritional management and even surgery in advanced
      cases, all of which provide varying results. This article discusses the diagnosis
      and treatment of EPS, it encourages the participation in the European Registry
      and it advocates the need to centralise the management of this medical
      complication.

PMID- 23169354
TI  - Metabolic acidosis and progression of chronic kidney disease: incidence,
      pathogenesis, and therapeutic options.
AB  - In the chronic kidney disease population metabolic acidosis is prevalent
      presenting already in the early stages of renal dysfunction. The pathogenesis
      associates the lack of bicarbonate production with the accumulation of
      organic/inorganic acids and the development of tubulointerstitial damage through
      ammonium retention and complement deposition. The empiric use of oral sodium
      bicarbonate represents an interesting therapeutic option that has been documented
      in a few clinical trials in human subjects. The availability of oral sodium, in
      its diverse forms, represents an inexpensive and simple way of treating an entity
      that could hasten the progression of kidney disease, as well as protein
      catabolism, bone disease and mortality.

PMID- 23169355
TI  - Evaluation of spiritual well-being in haemodialysis patients.
AB  - INTRODUCTION: Spirituality can be defined as a personal search for meaning and
      purpose in life that may or may not encompass religion. In this article we report
      on the development and testing of an instrument for measuring spiritual well
      being within a sample of haemodialysis patients. MATERIAL AND METHOD: The main
      instrument, a 21-item Meaning in Life Scale (MiLS), comprises four scales: Life
      Perspective, Purpose and Goals, Confusion and Lessened Meaning, Harmony and
      Peace, and Benefits of Spirituality. A total score for spiritual well-being is
      also produced. We also used the following variables: clinical (time on
      haemodialysis, modified Charlson comorbidity index), sociodemographic (age,
      gender), and self-assessments of health, quality of life (general and recent),
      personal happiness, religiosity, and belief in the afterlife. A cross-sectional
      study was carried out on 94 haemodialysis patients. RESULTS: This study
      demonstrates that the MiLS-Sp is a psychometrically sound measure of spiritual
      well-being for dialysis patients (reliability, validity) as they manage the
      complex demands of a chronic illness. Spiritual well-being was significantly
      associated with various quality of life variables, health status, personal
      happiness, or religiosity in patients on dialysis. There was no relationship
      between spirituality scores and comorbidity, HD duration, gender, or age.
      Spiritual well-being is relatively low in dialysis patients. CONCLUSION:
      Spirituality may play an important role on psychological well-being, quality of
      life, and self-rated health for patients on haemodialysis. Spiritual well-being
      in these patients is relatively low. Results suggest that assessing and
      addressing spiritual well-being in dialysis patients may be helpful in clinical
      practice.

PMID- 23169356
TI  - Epidemiological study of 7316 patients on haemodialysis treated in FME clinics in
      Spain, using data from the EuCliD(r) database: results from years 2009-2010.
AB  - Observational study of patients on hemodialysis (HD) in FMC(r) Spain clinics over
      the years 2009 and 2010. The data were collected from the EuClid(r) database,
      implemented in the clinics of FMC(r), which complies with the following feature:
      record online, compulsory, conducted in patients incidents and that it covers the
      entire population on HD in these clinics. Its aim is to understand the
      characteristics of patients and treatment patterns, comparing them with other
      studies described in the literature and in order to improve their prognosis and
      quality of life. Include 2637 incidents patients and 4679 prevalent, which makes
      a total of 7316 patients. In prevalent patients: 24.4% were diabetic; 76.3% had
      cardio-vascular disease (CVD) and 13.4% cancer. Among the incidents, these
      percentages were: 33.5% diabetic; 80.6% had CVD and 12.6% cancer. The prevalent
      patients had such as vascular access: FAV 68.5%, prosthesis 5.6%, permanent
      catheter 23.7% and 2.3% temporary catheter. The average of the duration of the
      sessions of HD was 230 minutes. 23.2% of the prevalent patients were on on-line
      hemodiafiltration. These patients hospitalization rates were 0.46
      hospitalizations per incident patient per year and 0.52 per prevalent patient per
      year. The annual gross mortality rate was 12%. The mortality of the patients in
      this study HD is smaller than these of the Spanish Registry of Dialysis and
      Transplant (GRER). The result of morbidity and mortality of the FMC clinics of
      Spain can, therefore, be as good compared with these of the GRER and other
      international series. That does not mean that there are not areas of improvement
      as the increase in the time of dialysis, the percentage of patients on on-line
      hemodiafiltration convective techniques and the percentage of FAV.

PMID- 23169357
TI  - Development of a program for kidney transplants using organs donated from donors
      awaiting cardiac arrest (type III Maastricht).
AB  - INTRODUCTION: The availability of organ donors is a limiting factor for kidney
      transplants. Donations from non-heart-beating donors (NHBD) can provide as many
      as one-third of all organs. Controlled patients awaiting cardiac arrest following
      limitation of life support techniques, or type III Maastricht donors, constitute
      an alternative that still has yet to be systematically developed. STUDY TYPE:
      Descriptive series of 10 cases occurring between January and April 2012. METHOD:
      Over a period of 6 months, we designed a protocol for extracting and managing
      kidney transplants and providing immunosuppression therapy. Patients are
      evaluated in accordance with the criteria agreed by a different team responsible
      for transplant coordination. We established a maximum duration of time between
      limitation of life-sustaining therapy and death of 120 minutes and 60 minutes
      warm ischaemia. Two types of graft perfusion were used, one in situ through
      direct application to the surgical area, and another using ante mortem vascular
      canalisation. Immunosuppression therapy included induction with thymoglobulin,
      steroids, and mycophenolate, with introduction of tacrolimus on the seventh day.
      Data are expressed as median and (range). RESULTS: We included the first 10 cases
      of kidney transplants with organs from 5 NHBD (type III Maastricht): 4 males,
      mean age of 57 years (45-66 years), with limitation of life-sustaining therapy
      due to anoxic encephalopathy (2), intoxication (1), acute stroke (2) and terminal
      respiratory failure (1). The following mean time intervals were recorded:
      effective warm ischaemia: 20 minutes (8-23 minutes) and cold ischaemia: 7.5 hours
      (4-14.1 hours). Recipients had a mean age of 58 years (32-71 years), with various
      aetiologies (2 cases of glomerulonephritis, 1 polycystic kidney disease, 2 tubulo
      interstitial nephropathy, 4 vascular, and 1 unknown), with a mean 31.7 months on
      haemodialysis (11-84 months); the kidney was a second transplant in two cases. No
      patients were hyper-immunised. Six patients required a dialysis session at some
      point, and four had prolonged acute tubular necrosis, over a mean hospitalisation
      period of 24.5 days (8-44 days). Mean creatinine (Cr) one month after
      transplantation was 2.1mg/dl (0.7-3.2mg/dl), and mean nadir creatinine was
      1.2mg/dl (0.7-3.2mg/dl). One patient did not improve upon Cr values <3.2mg/dl,
      despite the absence of evidence of toxicity or rejection in a renal biopsy, and
      the transplant pair reached a Cr of 1.4mg/dl. Throughout the series, similar
      surgical complications were recorded to those observed in conventional donor
      situations. CONCLUSIONS: Despite the limitations of this preliminary study, the
      use of this type of transplant produces favourable short-term evolution. Expanded
      use of this type of donor could reduce the waiting-list time for a kidney
      transplant.

PMID- 23169358
TI  - Kidney transplantation with grafts from type III Maastricht non-beating-heart
      donors.
AB  - Kidney transplantation (KT) with kidneys from non-beating-heart donors (NBHD) is
      a growing trend in Spain. The majority of these kidneys come from type II
      Maastricht patients, although in recent years, organ donations from patients
      awaiting cardiac arrest following limitation of life-sustaining therapy has
      already been in practice in certain European and North American countries,
      involving type III Maastricht patients. We present a series of 6 KT using kidneys
      from NHBD as a consequence of limitation of life-sustaining therapy in three
      different hospitals in the sector of Malaga. After agreeing upon a protocol for
      evaluating the potential of a patient for organ donation after the decision for
      limiting life-sustaining therapy, the patients' families were given the option of
      organ donation. Kidneys were preserved using a Porges double balloon catheter,
      which was placed prior to cardiac arrest. In two cases, the limitation of life
      sustaining therapy took place in the intensive care unit, and in the third case,
      in the operating room. The interval between limitation of life-sustaining therapy
      and cardiac arrest ranged between 15 minutes and 40 minutes, with an interval of
      circulatory arrest prior to perfusion of 5-11 minutes. Perfusion-cooling of the
      kidneys was initially carried out using saline solution, followed by organ
      preservation solution (Celsior or Belzer) and extraction of the kidney using a
      rapid surgical technique. True or functional hot ischaemia times were 60 minutes,
      59 minutes, and 50 minutes, respectively, for each of the three donors. Kidneys
      were evaluated for viability using time intervals for the procedure (including
      hypotension prior to cardiac arrest), macroscopic appearance, and histopathology
      of a sample taken from each kidney. The recipients of these 6 kidneys had given
      their consent to receive organs from expanded-criteria donors. Cold ischaemia
      lasted between 9 hours and 20 hours (mean: 14.6 hours). One recipient developed
      haemorrhagic complications during the immediate postoperative period and required
      a transplantectomy. The other five currently retain functioning grafts. All had
      delayed graft function, necessitating haemodialysis. The range of estimated
      glomerular filtration rates at the most recent follow-up evaluation was 23.0-106
      ml/min/1.73 m(2). In conclusion, type III Maastricht donors provide valid kidneys
      for transplantation, although this series showed that supported functional hot
      ischaemia was very important, the consequence of accumulated ischaemic damage
      starting in the agonal phase, circulatory arrest, and organ preservation using
      cold solutions. As such, to improve the quality of results obtained using kidneys
      from these types of donors would involve a very careful selection of optimal
      donors and minimisation of total functional ischaemia times.

PMID- 23169359
TI  - Maintaining residual renal function in patients on haemodialysis: 5-year
      experience using a progressively increasing dialysis regimen.
AB  - INTRODUCTION: In contrast to patients treated with peritoneal dialysis, those on
      periodical haemodialysis (HD) do not receive programmed progressive increases in
      dialysis dosage, nor is residual renal function taken into account in the
      calculation of the total dialysis prescription; rather, only dialyser clearance
      is factored into the equation. In 2006, we decided to establish a progressively
      increasing dialysis regimen at the start of renal replacement therapy, evaluating
      the possibility of starting with 2 sessions of HD/week when renal clearance of
      urea was equal to or greater than 2.5 ml/min. This study summarises our
      experience during the first 5 years of application of this progressively
      increasing HD prescription and its repercussions on residual renal function.
      METHODS: We included all patients who started periodical HD between 1/1/2006 and
      30/9/2010 and remained on dialysis for more than three months. The follow-up
      period ended on 31/12/2010 (study end date). When a patient started HD, urea and
      creatinine clearance levels were measured based on urea and creatinine
      concentrations in blood samples taken before dialysis and in urine samples taken
      24 hours prior to starting the first dialysis session of the week. If urea
      clearance was equal to or greater than 2.5 ml/min, 2 sessions of HD per week were
      applied, as long as the patient's clinical situation allowed for it (according to
      the criteria of the attending physician). Residual renal function was analysed
      every 2 months until diuresis was less than 100ml/day, which is considered to be
      basically null. We evaluated the decrease in residual renal function, calculating
      the rate of decrease in glomerular filtration (ml/min/month) and 24-hour diuresis
      (ml/month) in patients receiving 2 and 3 HD sessions per week. In January 2010,
      we took a cross-sectional sample, evaluating glomerular filtration and how this
      value was associated with various clinical and laboratory parameters in patients
      receiving 2 or 3 dialysis sessions per week. RESULTS: During the study period, 95
      patients were included in the study, 41 of which (43%) started with 2 HD sessions
      per week, and 54 (57%) with 3 sessions per week. The mean time that patients
      remained on the 2HD sessions/week regimen was 11.1 +/- 7.2 months (range: 2-25
      months). Of the 41 patients that started with 2 HD sessions/week, 10 received a
      transplant while on the treatment regimen, 1 was transferred to peritoneal
      dialysis, 6 recovered renal function and were able to abandon dialysis treatment,
      15 were switched to the 3 HD sessions/week regimen, and 9 continued on the 2 HD
      sessions/week regimen at the time the study ended. Of the 15 patients that were
      switched to the 3 HD sessions/week regimen, 4 received transplants, 3 died, and
      the remaining 8 continued on HD until the end of the study. A Kaplan-Meier
      survival analysis revealed that patients who started on the 2 HD sessions/week
      regimen had a greater survival rate (log-rank: 3.964; P=.04). Losses in both
      glomerular filtration rate and 24-hour diuresis were lower in patients on the 2
      HD sessions/week regimen: 0.22 +/- 0.36 ml/min/month vs 0.89 +/- 1.26
      ml/min/month for glomerular filtration (P=.001), and 90.59 +/- 132 ml/month vs
      206.23 +/- 286 ml/month for 24-hour diuresis (P=.001), respectively. In the cross
      sectional sample taken in January 2010, 17 patients were on the 2 HD
      sessions/week regimen and 47 were on the 3 HD sessions/week regimen. Serum
      concentrations of beta2-microglobulin were significantly lower in the 2 HD
      sessions/week group (19.7 +/- 5 vs 38.3 +/- 13; P=.000). The mean haemoglobin
      concentration was similar between the two groups, with a significantly lower dose
      required of erythropoietin in patients on the 2 HD sessions/week regimen (7058 +/
      3749 units/week vs 12 553 +/- 10 826 units/week; P=.037). CONCLUSION: In select
      populations, the start of HD can be administered on a progressively increasing
      dosage, starting with two sessions/week. In our experience, this is a safe
      prescription that probably contributes to preserving residual renal function.

PMID- 23169360
TI  - Renal function assessment in non-steroidal anti-inflammatory drug prescriptions.
      A pilot study in a primary care centre.
AB  - OBJECTIVES: To determine the current state of renal function monitoring carried
      out on patients treated with NSAIDs. MATERIAL AND METHOD: We selected patients
      from a Primary Care Centre who had received NSAIDs for the first time. We checked
      if renal function was measured and/or controlled 2 months pre/6 months post-NSAID
      administration in order to assess if patient renal function was known at the time
      of prescription and afterwards. RESULTS: During the study period, there were 42
      822 prescriptions made. Of these, 8611 were new drug prescriptions, of which 482
      (5.6%) were NSAIDs in patients older than 14 years of age. A total of 450
      patients (64% female) were treated with NSAIDs. Ibuprofen (66.0%) was the most
      commonly prescribed. NSAIDs were more frequently used in patients between 14-45
      years of age. Only 168 (37.1%) patients underwent any analytical tests over the
      course of the study (68% female). Before prescription, renal function was
      measured in only 14% of cases (63 patients). Two patients received NSAIDs despite
      having high serum creatinine levels. During the follow-up, serum creatinine was
      measured in 129 patients (28.7%). CONCLUSIONS: In primary care, NSAIDs represent
      a substantial percentage of the drugs prescribed (5.6%). Ibuprofen is the most
      commonly prescribed. NSAIDs are more frequently used in women between 14-45
      years. Musculo-skeletal pain is the main indication for prescription. Only 14% of
      patients receiving these drugs had previously measured levels of serum
      creatinine. These values are rarely taken into account when prescribing NSAIDs.
      Control of renal function after NSAID prescription was unusual.

PMID- 23169361
TI  - Effect of dialysis modality and other prescription factors on peritoneal protein
      excretion in peritoneal dialysis.
AB  - BACKGROUND: There is a deficit of information regarding the factors that
      influence peritoneal protein excretion (PPE) during PD therapy. In particular,
      the effects of the modality of PD and other conditions of the dialysis
      prescription remain unclear. METHOD: This prospective, observational study
      analysed the effects of prescription characteristics on 24-hour PPE (study
      variable) in a cohort of patients starting PD. Our statistical analysis included
      a multi-level mixed model and standardised estimations of peritoneal protein
      transport during serial four-hour peritoneal equilibrium tests in order to
      control for disparities in the characteristics of patients managed on different
      regimens. RESULTS: We evaluated 284 patients, 197 on CAPD and 87 on automated PD
      (APD), at the start of PD treatment. The two groups differed in terms of clinical
      characteristics and peritoneal function. Univariate, serial estimates of 24-hour
      PPE were marginally higher in CAPD patients, and remained essentially stable over
      time in both groups. Multivariate analyses identified CAPD (B=888.5mg, 95% CI:
      327.5/1448.6), total dialysate volume infused per day (B=275.9 mg/Ll;
      153.9/397.9) and ultrafiltration (B=0.41 mg/mL; 0.02/0.80) as independent
      predictors of 24-hour PPE. The model also revealed a minor trend for a lower 24
      hour PPE as time on PD increases. CONCLUSIONS: The individual characteristics of
      peritoneal protein transport are the major determinants of 24-hour PPE. The use
      of CAPD as the dialysis modality is associated with higher PPE rates than the APD
      technique, although this difference is counterbalanced by a direct correlation
      between PPE and the volume of dialysate infused per day. Ultrafiltration and time
      on dialysis also act as minor independent predictors of PPE during PD therapy.

PMID- 23169362
TI  - The effect of pentoxifylline on reduction of proteinuria among patients with type
      2 diabetes under blockade of angiotensin system: a double blind and randomized
      clinical trial.
AB  - Although blockade of renin-angiotensin system have been cited as the first line
      of therapy for the management of diabetic nephropathy (DN), however in a
      substantial number of patients, progression of renal disease are not completely
      halted by these agents. We have conducted a double blinded clinical trial to
      assess the additive effect of pentoxifylline on reduction of proteinuria among
      patients with type 2 DM under blockade of angiotensin system. The dosage of PTX
      used in our trial was at a low dosage of 400mg daily and to our knowledge, we did
      not found article which evaluated the antiproteinuric effect of pentoxifylline in
      this dosage. One hundred patients with DN and persistent proteinuria despite
      treatment with losartan and enalapril in at least 3 months before inclusion in
      the study were randomly assigned to two groups. Control group (n=50, 26 males and
      24 females) received losartan and enalapril, while treatment group (PTX Group)
      (n=50, 28 males and 22 females) was given losartan, enalapril and pentoxifylline
      400mg/day for 6 months. At the beginning of the study there were no significant
      differences in demographic and clinical characteristics of patients including
      serum creatinine, HbA1c, blood pressure and urinary protein excretion between two
      groups (P>.05). In the PTX group, the mean rate of urinary protein excretion have
      significantly decreased from 616.66mg to 378.24 after 3 months (P=.000) and to
      192.05mg after 6 months (P=.000) whereas no significant changes were observed in
      the control group. The beneficial antiproteinuric effect of PTX was not
      associated to the degree of metabolic control and a reduction of blood pressure.
      In addition, at the end of study, the mean clearance of creatinine was
      significantly higher in PTX group (P=.04). In conclusion, PTX can significantly
      provide additive antiproteinuric effect and slow the decrease in GFR among
      patients with type 2 DM under blockade of angiotensin system.

PMID- 23169363
TI  - Awareness and implementation in daily practice of the S.E.N.-semFYC consensus
      document on chronic kidney disease.
AB  - BACKGROUND: In 2007, the Spanish Society of Family and Community Medicine
      (semFYC) and the Spanish Society of Nephrology (S.E.N.) created a consensus
      document in order to reduce the variability in clinical practices for the
      detection, treatment, and referral of cases of chronic kidney disease (CKD).
      OBJECTIVES: To evaluate the level of awareness, dissemination, agreement, and
      application of the S.E.N.-semFYC consensus document on chronic kidney disease.
      METHOD: Ours was a cross-sectional, descriptive, and observational study carried
      out among 476 primary health care doctors and nephrologists using a survey.
      RESULTS: Of the 326 primary care doctors and 150 nephrologists surveyed, 51.1%
      and 89.6% respectively knew of the consensus document. A total of 70.8% of
      nephrologists considered the document to be highly necessary, and were very much
      in agreement with the content. Primary care doctors placed more value on the
      practical usefulness of the document (63.2% AP vs. 52.1% nephrologists).The
      sections that reported the greatest level of unfamiliarity among primary care
      doctors (>20% of those surveyed) included recommendations regarding the
      suitability of ultrasound examinations in male patients with CKD older than 60
      years of age and in regards to the criteria for patient referral to the
      nephrology department. The level of application of the recommendations set forth
      in the document varied widely between the two specialties, with greater
      compliance among nephrologists. Age, sex, field of medicine, professional
      experience, the population treated, and health care workload were not
      significantly associated with differences in awareness, perceived need, or
      application of the consensus document. CONCLUSIONS: This survey demonstrates that
      the level of implementation of the S.E.N.-sem- FYC consensus document for CKD has
      much room for improvement, above all among primary care physicians. The
      application of this consensus document can improve clinical practice. Several
      critical aspects have been identified in the evaluation and referral of patients
      with CKD that must be addressed through the establishment of strategies for
      disseminating information and continued training for the scientific societies
      involved in treating these patients.

PMID- 23169364
TI  - Cardiac troponin I and creatine kinase MB isoenzyme in patients with chronic
      renal failure.
AB  - OBJECTIVE: The aim of our study was to evaluate cut-off values for acute coronary
      syndrome (ACS) diagnosis in patients with chronic renal failure (CRF) for the
      cardiac biomarkers cardiac troponin I (cTnI) and creatine kinase MB isoenzyme (CK
      MB) as compared to the cut-off values proposed by the manufacturers and those
      frequently used in the laboratory. METHOD: We performed a prospective study in
      patients with CRF with a glomerular filtration rate estimated by the MDRD-4
      equation <60 mL/min and admitted with suspected acute coronary syndrome due to
      clinical history, physical examination, and electrocardiography. cTnI and CK-MB
      measurements were assessed upon hospitalisation and six months later using two
      different analytical methods (for cTnI: Access(r) and Vidas(r) analysers, and for
      CK-MB: Access(r) and Vitros(r) analysers). RESULTS: During the study period, 484
      patients with CRF and suspected ACS were assessed. ACS was diagnosed in 12% of
      patients (58/484), while we found other cardiac pathologies (OCP) in 29% of
      patients (140/484) and other non-cardiac pathologies (ONCP) in 59% of patients
      (286/484). For cTnI assessed using the Access(r) analyser with the usual cut-off
      value (>= 0.5 ng/mL), sensitivity was 43% and specificity was 94%, while for the
      proposed cut-off value (>= 0.11 ng/mL), the values were 68% and 83%,
      respectively. For cTnI assessed using the Vidas(r) analyser with the usual cut
      off value (>= 0.11 ng/mL), sensitivity was 64% and specificity was 87%, while for
      the proposed cut-off value (>= 0.06 ng/mL), the values were 75% and 79%,
      respectively. The sensitivity and specificity for both CK-MB were lower compared
      with cTnI. CONCLUSION: The cut-off values proposed in this study for both cTnI in
      patients with CRF (stage 3 to 5) to diagnose ACS are significantly different from
      that of the general population.

PMID- 23169365
TI  - Acute renal failure predictors in elderly patients with chronic kidney disease.
AB  - INTRODUCTION: Acute renal failure (ARF) is a very common problem in the elderly
      and is associated with high morbidity and mortality rates. This study analysed
      ARF predictors in a cohort of elderly subjects and their impact on the evolution
      of renal function. PATIENTS AND METHOD: A group of 80 elderly individuals were
      recruited between January and April 2006, and 56 of these who were still alive
      after 36 months were retrospectively studied, examining episodes of ARF, their
      causes, and the need for dialysis. RESULTS: Twelve patients (21.4%) developed
      ARF: 4 (33.3%) related to heart failure, 4 (33.3%) due to infection/sepsis, 2
      (16.7%) due to volume depletion, and another 2 were multifactorial (16.7%). No
      patients required dialysis therapy. Patients with ARF were older (P=.017), had
      worse renal function at baseline (P=.031), higher levels of uric acid (P=.002),
      and lower haematocrit (P=.003). Patients with ARF had a mean baseline serum
      creatinine of 1.57 +/- 0.59 mg/dl and peak creatinine levels during episodes of
      ARF averaged 4.25 +/- 4.26 mg/dl (P=.035). Mean renal function at 36 months in
      patients with ARF had decreased (P=.024). In a logistic regression analysis
      (independent variables: baseline MDRD, age, gender, Charlson index, serum
      creatinine, urea, and uric acid), age (RR: 1.20, 1.01-1.43, P=.039), uric acid
      (RR: 2.65, 1.11-6.30, P=.027), and haematocrit (RR: 0.64, 0.43-0.96, P=.031) were
      independently associated with the development of ARF. CONCLUSIONS: Baseline
      levels of uric acid and haematocrit are independent risk factors for the
      development of ARF in the elderly. Although these episodes may be functional in
      nature and not require dialysis, this can still cause a deterioration of renal
      function over time.

PMID- 23169366
TI  - Cholesterol atheroembolism and combined treatment with steroids and iloprost.
AB  - Cholesterol atheroembolism (CAE) is a systemic disorder whose incidence has
      increased in recent decades and that presents high morbidity and mortality.
      Although several therapeutic alternatives have been reported, there is no
      consensus about the best treatment for this disease. In this paper we report the
      case of a patient with CAE with skin, bowel and kidney involvement who presented
      a good response to combined therapy with steroids and prostaglandin analogues.
      Although there are no conclusive studies, we recommend this therapeutic
      alternative in the management of CAE with organic failure.

PMID- 23169367
TI  - A successful clinical case of encapsulating peritoneal sclerosis -surgical
      management using enterolysis.
AB  - The encapsulating peritoneal sclerosis is a rare but serious complication of
      peritoneal dialysis. The incident rate varies between 0.5 to 4.4%. This entity is
      associated with significant morbidity and mortality. The diagnosis requires the
      presence of clinical features of intestinal obstruction or disturbed
      gastrointestinal function with pathological and radiological evidence of bowel
      encapsulation. The exact pathogenic mechanism of EPS remains unknown, although
      it&rsquo;s strongest associated with duration of peritoneal dialysis. We present
      a clinical case of EPS and discuss the clinical manifestations, diagnosis,
      treatment, prognosis and prevention.

PMID- 23169369
TI  - Antidiabetics in chronic kidney disease: new questions to new and classical
      drugs.

PMID- 23169370
TI  - Discrepancies between the summary of characteristics and the recommended use of
      metformin in the treatment of type 2 diabetes mellitus patients.

PMID- 23169372
TI  - Autosomal dominant polycystic kidney disease with contralateral renal agenesis.

PMID- 23169373
TI  - Diabetic nephropathy confirmed by biopsy: on who and when do we have to perform a
      biopsy?

PMID- 23169374
TI  - Results of a renal transplant with multiple renal arteries in Veracruz, Mexico.

PMID- 23169375
TI  - Abandonment of peritoneal dialysis due to peritonitis: Have the responsible
      agents changed? Our experience.

PMID- 23169376
TI  - Proliferative glomerulonephritis with monoclonal IgG deposits on multiple
      myeloma.

PMID- 23169377
TI  - Amyloidosis AL with severe renal and cardiac involvement: a very rare association
      of terrible prognosis, two case reports.

PMID- 23169378
TI  - Post-transplant Henoch-Schonlein purpura de novo: clinical-histological
      discordance.

PMID- 23169379
TI  - Development of focal segmental glomerulosclerosis in a patient with polycythemia
      vera: can polycythemia vera be a cause of focal segmental glomerulosclerosis?

PMID- 23169380
TI  - Tubulointerstitial nephritis and sclerosing cholangitis associated with
      autoimmune pancreatitis.

PMID- 23169381
TI  - Acute kidney injury induced by allergic conditions-associated renal cholesterol
      crystal embolism.

PMID- 23169382
TI  - Percutaneous closure of arteriovenous fistula for haemodialysis due to venous
      hypertension secondary to subclavian vein occlusion.

PMID- 23169383
TI  - Pregnancy in haemodialysis patient.

PMID- 23169384
TI  - Tacrolimus associated to posterior reversible atypical encephalopathy syndrome
      and brain haemorrhage in renal transplant recipient.

PMID- 23169385
TI  - Peripheral nervous system involvement in a haemodialysis patient treated with
      pegylated interferon.

PMID- 23169386
TI  - Renal amyloidosis due to hyper-IgD syndrome.

PMID- 23169387
TI  - Excited-state proton coupled charge transfer modulated by molecular structure and
      media polarization.
AB  - Charge and proton transfer reactions in the excited states of organic dyes can be
      coupled in many different ways. Despite the complementarity of charges, they can
      occur on different time scales and in different directions of the molecular
      framework. In certain cases, excited-state equilibrium can be established between
      the charge-transfer and proton-transfer species. The interplay of these reactions
      can be modulated and even reversed by variations in dye molecular structures and
      changes of the surrounding media. With knowledge of the mechanisms of these
      processes, desired rates and directions can be achieved, and thus the multiple
      emission spectral features can be harnessed. These features have found versatile
      applications in a number of cutting-edge technological areas, particularly in
      fluorescence sensing and imaging.

PMID- 23169388
TI  - An efficient single-enzymatic cascade for asymmetric synthesis of chiral amines
      catalyzed by omega-transaminase.
AB  - An efficient single-enzymatic cascade approach for the asymmetric synthesis of
      chiral amines has been developed, which applies the amino donor 3-aminocyclohexa
      1,5-dienecarboxylic acid spontaneously tautomerizing to reach reaction completion
      with excellent ee values.

PMID- 23169389
TI  - Importance of the lung perfusion scintigraphy in single lung transplantation.
AB  - Lung perfusion scintigraphy (LPS) with (99m)Tc-MAA gives valuable information
      about patients who will undergo a single lung transplantation. This technique
      makes it possible to evaluate and quantify the relative function of both lungs to
      select the organ to be transplanted. Once the surgery has been performed, the LPS
      represents a diagnostic method to study the status of the transplanted organ. Two
      patients who underwent single lung transplantation were studied in our hospital.
      In both cases, a pre-operative LPS was performed before surgery for selection of
      the organ to be transplanted and the scintigraphy study was performed a few
      months after transplantation to establish the perfusion function of the
      transplanted lung.

PMID- 23169390
TI  - Atypical uptake of 99m Tc-HMDP in a patient with metastatic liver disease.

PMID- 23169391
TI  - Role of nuclear medicine in staging and management in a case of Merkel cell
      carcinoma.

PMID- 23169392
TI  - Role of 18F-FDG PET-CT in the study of sacrococcygeal chordoma.

PMID- 23169393
TI  - Why risk professional fulfilment: a grounded theory of physician engagement in
      healthcare development.
AB  - The need for trans-professional collaboration when developing healthcare has been
      stressed by practitioners and researchers. Because physicians have considerable
      impact on this process, their willingness to become involved is central to this
      issue. OBJECTIVE: This study aims to gain a deeper understanding of how
      physicians view their engagement in healthcare development. METHOD: Using a
      grounded theory approach, the study developed a conceptual model based on
      empirical data from qualitative interviews with physicians working at a hospital
      (n = 25). RESULTS: A continual striving for experiences of usefulness and
      progress, conceptualized as 'striving for professional fulfilment' (the core
      category), emerged as a central motivational drive for physician engagement in
      healthcare development. Such experiences were gained when achieving meaningful
      results, having impact, learning to see the greater context and fulfilling the
      perceived doctor role. Reinforcing organizational preconditions that facilitated
      physician engagement in healthcare development were workplace continuity,
      effective strategies and procedures, role clarity regarding participation in
      development and opportunities to gain knowledge about organization and
      development. Two opposite role-taking tendencies emerged: upholding a traditional
      doctor role with high autonomy in relation to organization and management,
      clinical work serving as the main source of fulfilment, or approaching a more
      complete 'employeeship' role in which organizational engagement also provides a
      sense of fulfilment. CONCLUSION: Experiencing professional fulfilment from
      participation in healthcare development is crucial for sustainable physician
      engagement in such activities.

PMID- 23169394
TI  - Exome sequencing identifies a branch point variant in Aarskog-Scott syndrome.
AB  - Aarskog-Scott syndrome (ASS) is a rare disorder with characteristic facial,
      skeletal, and genital abnormalities. Mutations in the FGD1 gene (Xp11.21) are
      responsible for ASS. However, mutation detection rates are low. Here, we report a
      family with ASS where conventional Sanger sequencing failed to detect a
      pathogenic change in FGD1. To identify the causative gene, we performed whole
      exome sequencing in two patients. An initial analysis did not reveal a likely
      candidate gene. After relaxing our filtering criteria, accepting larger intronic
      segments, we unexpectedly identified a branch point (BP) variant in FGD1.
      Analysis of patient-derived RNA showed complete skipping of exon 13, leading to
      premature translation termination. The BP variant detected is one of very few
      reported so far proven to affect splicing. Our results show that besides digging
      deeper to reveal nonobvious variants, isolation and analysis of RNA provides a
      valuable but under-appreciated tool to resolve cases with unknown genetic
      defects.

PMID- 23169395
TI  - The prognostic value of E-cadherin in gastric cancer: a meta-analysis.
AB  - The prognostic impact of E-cadherin downregulation in gastric cancer has been
      assessed for years while the results are controversial and heterogeneous. We thus
      comprehensively reviewed the evidence for evaluation of E-cadherin expression in
      gastric cancer to determine this effect. We searched PubMed and Embase to
      identify eligible studies, and 26 studies comprising 4,383 gastric cancer
      patients were included to assess the association between E-cadherin
      immunohistochemical expression and overall survival (OS) and clinicopathological
      characteristics. Summary hazard ratios (HRs) or odds ratios (ORs) with 95%
      confidence interval (95% CI) were calculated to estimate the effect. We also
      performed meta-regression and subgroup analysis according to study location,
      publication year, number of patients, quality score of studies and cut-off value.
      Reduced E-cadherin expression was significantly correlated with poor OS of
      gastric cancer patients (HR 1.62, 95% CI 1.34-1.96). Subgroup analysis indicated
      that E-cadherin low-expression had an unfavorable impact on OS in Asian patients
      (HR 1.87, 95% CI 1.45-2.41). Moreover, downregulation of E-cadherin was
      significantly associated with TNM stage (OR 2.52, 95% CI 1.85-3.43), the depth of
      invasion (OR 2.01, 95% CI 1.39-2.90), lymph node metastasis (OR 2.39, 95% CI 1.68
      3.40), distant metastasis (OR 2.23, 95% CI 1.21-4.11), grade of differentiation
      (OR 2.26, 95% CI 1.60-3.21), vascular invasion (OR 1.86, 95% CI 1.10-3.13) and
      histological type of gastric cancer (OR 4.22, 95% CI 2.96-6.02). This meta
      analysis revealed that E-cadherin expression might be a predicative factor of
      poor prognosis for gastric cancer particularly in Asia.

PMID- 23169396
TI  - Bringing evidence-based interventions to the field:  the fidelity challenge.
AB  - Fidelity of implementation in replicating evidence-based health promotion
      interventions, to ensure implementation as designed and proven through research,
      is crucial if evidence-based community and population health interventions are to
      achieve promised results but can be difficult to attain in practice. This article
      highlights major challenges, considerations, and strategies associated with
      fidelity as public health care practitioners implement evidence-based
      interventions and bring them to scale in the field. There is need for sharing
      information about "what works" in implementing these interventions with fidelity,
      as well sharing information about implementation challenges and improvements to
      intervention design. Fidelity is important if practitioners are to obtain results
      and outcomes planned by intervention developers and is an essential value
      proposition for evidence-based public health practice and population health
      improvement.

PMID- 23169397
TI  - Public health accreditation and metrics for ethics:  a case study on
      environmental health and community engagement.
AB  - As public health departments around the country undergo accreditation using the
      Public Health Accreditation Board standards, the process provides a new
      opportunity to integrate ethics metrics into day-to-day public health practice.
      While the accreditation standards do not explicitly address ethics, ethical tools
      and considerations can enrich the accreditation process by helping health
      departments and their communities understand what ethical principles underlie the
      accreditation standards and how to use metrics based on these ethical principles
      to support decision making in public health practice. We provide a crosswalk
      between a public health essential service, Public Health Accreditation Board
      community engagement domain standards, and the relevant ethical principles in the
      Public Health Code of Ethics (Code). A case study illustrates how the
      accreditation standards and the ethical principles in the Code together can
      enhance the practice of engaging the community in decision making in the local
      health department.

PMID- 23169398
TI  - Rules and tools that improved vaccines for children vaccine-ordering practices in
      Oregon:  a 2010 pilot project.
AB  - OBJECTIVE: This project's objective was to enhance efforts to improve vaccine
      ordering efficiencies among targeted clinics using publicly purchased vaccines.
      DESIGN: Using an assessment of ordering behavior developed by the Centers for
      Disease Control and Prevention, we selected and trained immunization providers
      and assessed improvements in ordering behavior by comparing ordering patterns
      before and after the intervention. SETTING: A total of 144 Vaccines for Children
      program providers in Oregon. PARTICIPANTS: We assessed 144 providers trained in
      the Economic Order Quantity process between January and November 2010.
      INTERVENTION (IF APPLICABLE): Providers were invited to participate in regional
      trainings. Trainings included assignment of ordering frequency and dissemination
      of tools to support adherence to the recommended ordering frequency. MAIN OUTCOME
      MEASURE(S): The percent increase in targeted clinics ordering according to
      recommended order frequency and the resulting decrease in orders placed, as an
      outcome of training and ordering tools. RESULTS: Only 35% of targeted providers
      were ordering according to the recommended ordering frequency before the project
      began. After completing training, utilizing ordering tools and ordering over a 7
      month period, 78% of the targeted clinics were ordering according to the
      recommended frequency, a 120% increase in the number of clinics ordering with the
      recommended frequency. At baseline, targeted clinics placed 915 total vaccine
      orders over a 7-month period. After completing training and participating in the
      Economic Order Quantity process, only 645 orders were placed, a reduction of 30%
      . CONCLUSIONS: The initiative was successful in reducing the number of orders
      placed by Vaccines for Children providers in Oregon. A previous effort to reduce
      ordering, without the use of training or tools, did not achieve the same levels
      of provider compliance, suggesting that the addition of staff and development of
      tools were helpful in supporting behavior change and improving providers' ability
      to adhere to assigned order frequencies. Reducing order frequency results in more
      efficient vaccine ordering patterns and benefits vaccine distributors, Oregon
      Immunization Program staff, and provider staff.

PMID- 23169399
TI  - Disparities in the severity of influenza illness: a descriptive study of
      hospitalized and nonhospitalized novel H1N1 influenza-positive patients in New
      York City: 2009-2010 influenza season.
AB  - OBJECTIVE: To investigate the association between socioeconomic status (SES) and
      hospitalization for 2009 H1N1 influenza, independently of access to care and
      known risk factors for severe influenza illness, among New York City residents
      during the 2009-2010 influenza season. DESIGN: We used a 1:2 case-control study
      design, matching by age group and month of diagnosis. Cases were defined as
      laboratory-confirmed patients with 2009 H1N1 influenza who were hospitalized
      during their illness. Controls were defined as nonhospitalized laboratory
      confirmed influenza A patients. Participants were contacted for a telephone
      interview to collect relevant clinical and demographic data. We used conditional
      logistic regression to analyze the association between SES and hospitalization.
      SETTING: New York City. PARTICIPANTS: Of the 171 hospitalized cases who were
      identified between October 2009 and February 2010, a total of 128 completed
      telephone interviews. A total of 640 nonhospitalized controls were contacted, and
      of these, 337 completed interviews. MAIN OUTCOME MEASURES: The main outcome of
      interest was whether or not a patient was hospitalized during his or her 2009
      H1N1 influenza illness. Socioeconomic status was measured using education and
      neighborhood poverty. RESULTS: We identified a gradient in the odds of
      hospitalization for 2009 H1N1 influenza by education level among adults. This
      association could not be entirely explained by access to care and underlying risk
      factors. An inverse association between odds of hospitalization and neighborhood
      poverty was also identified among adults and children. CONCLUSIONS: This study
      suggests that individuals of lower SES were more vulnerable to severe illness
      during the 2009 H1N1 pandemic. Additional research is needed to help guide
      interventions to protect this population during future influenza pandemics.

PMID- 23169400
TI  - State legislators' work on public health-related issues:  what influences
      priorities?
AB  - CONTEXT: Policies are an effective way to influence population health and prevent
      disease. Unfortunately, public health research is often not well translated for
      policy audiences. Furthermore, researchers seeking to influence policy face an
      incomplete understanding of what influences legislators' decisions regarding
      which issues will receive their limited time and focus. OBJECTIVE: The objective
      of this analysis was to examine various factors that may influence state
      legislators' decisions about which health issues they address. DESIGN: Cross
      sectional analysis of data collected from a randomized trial. SETTING: State
      legislatures. PARTICIPANTS: State-level legislators. MAIN OUTCOME MEASURE(S):
      Measures included a rating of the influence of various factors on health policy
      priorities. A 7-point scale was used to measure political ideology on social and
      fiscal issues. Standard demographic questions were included on age, gender, and
      level of education. RESULTS: Seventy-five legislators completed surveys. Sixty
      three percent were aged 55 years or older, and 76% male. When they were asked to
      rate factors according to importance in determining what health issues to work
      on, the top-rated factor was constituents' needs or opinions followed by evidence
      of scientific effectiveness. Ratings were also examined by subgroups.
      CONCLUSIONS: These findings point to several important applications for public
      health practitioners and researchers. Because legislators value constituents'
      opinions, it is critical to inform and educate constituents about public health
      issues as well as policy options that may be effective in addressing problems.
      The results also highlight the importance of public health researchers and
      practitioners improving dissemination efforts to ensure that evidence-based
      scientific information is shared with policymakers in an effective and timely
      manner.

PMID- 23169401
TI  - Designing the framework for competency-based master of public health programs in
      India.
AB  - Competency in the practice of public health is the implicit goal of education
      institutions that offer master of public health (MPH) programs. With the
      expanding number of institutions offering courses in public health in India, it
      is timely to develop a common framework to ensure that graduates are proficient
      in critical public health. Steps such as situation assessment, survey of public
      health care professionals in India, and national consultation were undertaken to
      develop a proposed competency-based framework for MPH programs in India. The
      existing curricula of all 23 Indian MPH courses vary significantly in content
      with regard to core, concentration, and crosscutting discipline areas and course
      durations. The competency or learning outcome is not well defined. The findings
      of the survey suggest that MPH graduates in India should have competencies
      ranging from monitoring of health problems and epidemics in the community,
      applying biostatistics in public health, conducting action research,
      understanding social and community influence on public health developing
      indicators and instruments to monitor and evaluate community health programs,
      developing proposals, and involving community in planning, delivery, and
      monitoring of health programs. Competency statements were framed and mapped with
      domains including epidemiology, biostatistics, social and behavioral sciences,
      health care system, policy, planning, and financing, and environmental health
      sciences and a crosscutting domain that include health communication and
      informatics, health management and leadership, professionalism, systems thinking,
      and public health biology. The proposed competency-based framework for Indian MPH
      programs can be adapted to meet the needs of diverse, unique programs. The
      framework ensures the uniqueness and diversity of individual MPH programs in
      India while contributing to measures of overall program success.

PMID- 23169402
TI  - Communicating about vaccines and vaccine safety:  what are medical residents
      learning and what do they want to learn?
AB  - OBJECTIVE: Physicians spend significant amounts of time discussing vaccine safety
      concerns with patients and parents. This study aimed to better understand the
      educational needs of US residents regarding vaccine safety communication,
      primarily by quantifying the vaccine safety communication training that residents
      currently receive and elucidating residents' preferences around education about
      vaccines and vaccine safety communication. DESIGN: A mixed-methods needs
      assessment consisting of focus groups and a survey. SETTING/PARTICIPANTS: A
      convenience sample of 303 medical residents in pediatrics, family medicine, and
      internal medicine from across the United States participated in an online,
      anonymous survey from March through June 2010. In addition, 9 focus groups with
      47 resident participants were held. MAIN OUTCOME MEASURES/RESULTS: The sample
      included residents in pediatrics (239, 80.2%), internal or family medicine (30,
      10.1%), and dual medicine-pediatrics (29, 9.7%); 20.6% of the residents reported
      "not learning" about vaccine safety communication in their residency programs.
      Preferred learning methods, which were also the most commonly used methods,
      included didactic lectures and role-modeling/cases. Electronic teaching method
      were not only less desired but also very rarely utilized. More than 95% of
      residents reported thinking that vaccine safety communication would be very or
      somewhat important in their careers. CONCLUSIONS: Improving education on vaccine
      safety communication within US residency programs, as well as offering self
      learning opportunities, can better prepare physicians for their careers.

PMID- 23169403
TI  - Educating the future public health workforce:  do schools of public health teach
      students about the private sector?
AB  - CONTEXT: Recent surveys indicate that approximately 40% of graduates from schools
      of public health are employed within the private sector or have an employer
      charged with regulating the private sector. These data suggest that schools of
      public health should provide curricular opportunities for their students--the
      future public health workforce--to learn about the relationship between the
      private sector and the public's health. OBJECTIVE: To identify opportunities for
      graduate students in schools of public health to select course work that educates
      them about the relationship between the private sector and public health. DESIGN:
      We systematically identified and analyzed data gathered from publicly available
      course titles and descriptions on the Web sites of accredited schools of public
      health. SETTING: Data were collected in the United States. PARTICIPANTS: The
      sample consisted of accredited schools of public health. MAIN OUTCOME MEASURES:
      Descriptions of the number and types of courses that schools of public health
      offer about the private sector and identification of how course descriptions
      frame the private sector relative to public health. RESULTS: We identified 104
      unique courses with content about the private sector's relationship to public
      health. More than 75% of accredited schools of public health offered at least 1
      such course. Nearly 25% of identified courses focused exclusively on the health
      insurance industry. Qualitative analysis of the data revealed 5 frames used to
      describe the private sector, including its role as a stakeholder in the policy
      process. CONCLUSIONS: Schools of public health face a curricular gap, with
      relatively few course offerings that teach students about the relationship
      between the private sector and the public's health. By developing new courses or
      revising existing ones, schools of public health can expose the future public
      health workforce to the varied ways public health professionals interact with the
      private sector, and potentially influence students' career paths.

PMID- 23169404
TI  - Variation in delivery of the 10 essential public health services by local health
      departments for obesity control in 2005 and 2008.
AB  - OBJECTIVES: To describe and compare the capacity of local health departments
      (LHDs) to perform 10 essential public health services (EPHS) for obesity control
      in 2005 and 2008, and explore factors associated with provision of these
      services. METHODS: The data for this study were drawn from the 2005 and 2008
      National Profile of Local Health Department surveys, conducted by the National
      Association of County and City Health Officials. Data were analyzed in SAS
      version 9.1 (SAS Institute Inc, Cary, North Carolina). RESULTS: The proportion of
      LHDs that reported that they do not provide any of the EPHS for obesity control
      decreased from 27.9% in 2005 to 17.0% in 2008. In both 2005 and 2008, the 2 most
      frequently provided EPHS for obesity control by LHDs were informing, educating,
      and empowering the people (EPHS 3) and linking people to needed personal health
      services (EPHS 7). The 2 least frequently provided services were enforcing laws
      and regulations (EPHS 6) and conducting research (EPHS 10). On average, LHDs
      provided 3.05 EPHS in 2005 and 3.69 EPHS in 2008. Multiple logistic regression
      results show that LHDs with larger jurisdiction population, with a local
      governance, and those that have completed a community health improvement plan
      were more likely to provide more of the EPHS for obesity (P < .05). CONCLUSIONS:
      The provision of the 10 EPHS for obesity control by LHDs remains low. Local
      health departments need more assistance and resources to expand performance of
      EPHS for obesity control. Future studies are needed to evaluate and promote LHD
      capacity to deliver evidence-based strategies for obesity control in local
      communities.

PMID- 23169405
TI  - Interest in public health careers among undergraduate student nurses.
AB  - CONTEXT: Public health workforce trends demonstrate threats to a vital national
      resource. The current shortage of public health nurses is due to a variety of
      factors. One route to addressing the public health nursing shortage is to
      increase the level of interest in public health as a career option for nurses.
      OBJECTIVE: The main objective of this study was to examine the relationship of
      nursing education program and field experience characteristics on the level of
      interest in a public health career among student nurses. DESIGN: Cross-sectional,
      online surveys of undergraduate student nurses were conducted over 6 semesters to
      assess the relationship of field practicum characteristics and level of interest
      in a public health career. SETTING: Undergraduate student nurses (N = 882)
      enrolled in traditional baccalaureate nursing programs (n = 18) and online
      associate to baccalaureate degree completion programs (n = 2) in one US state
      participated in the survey after completing the required community or public
      health coursework and field experiences. MAIN OUTCOME MEASURE: Level of interest
      in a career in public health was measured using a 4-point Likert-type scale
      anchored by "no interest" and "very strong interest." RESULTS: Overall, 46% of
      respondents expressed either moderate or strong interest in a future career in
      public health. Having had a field experience in a local health department was the
      only type of experience associated with stronger interest in a public health
      career. Enrollment in baccalaureate completion programs was associated with
      higher interest, and enrollment in programs located in a region of the state
      where students were significantly less likely to have field experiences in local
      health departments was associated with lower interest. CONCLUSION: Career
      interests for nurses are developed in part through field experiences while in
      nursing school. Interest in public health careers may be nurtured through field
      experiences in local health departments.

PMID- 23169406
TI  - Public health emergency preparedness: lessons learned about monitoring of
      interventions from the National Association of County and City Health Official's
      survey of nonpharmaceutical interventions for pandemic H1N1.
AB  - OBJECTIVES: We assessed local health departments' (LHDs') ability to provide data
      on nonpharmaceutical interventions (NPIs) for the mitigation of 2009 H1N1
      influenza during the pandemic response. DESIGN: Local health departments
      voluntarily participated weekly in a National Association of County and City
      Health Officials Web-based survey designed to provide situational awareness to
      federal partners about NPI recommendations and implementation during the response
      and to provide insight into the epidemiologic context in which recommendations
      were made. SETTING: Local health departments during the fall 2009 H1N1 pandemic
      response. PARTICIPANTS: Local health departments that voluntarily participated in
      the National Association of County and City Health Officials Sentinel
      Surveillance Network. MAIN OUTCOME MEASURES: Local health departments were asked
      to report data on recommendations for and the implementation of NPIs from 7
      community sectors. Data were also collected on influenza outbreaks; closures,
      whether recommended by the local health department or not; absenteeism of
      students in grades K-12; the type(s) of influenza viruses circulating in the
      jurisdiction; and the health care system capacity. RESULTS: One hundred thirty
      nine LHDs participated. Most LHDs issued NPI recommendations to their community
      over the 10-week survey period with 70% to 97% of LHDs recommending hand hygiene
      and cough etiquette and 51% to 78% voluntary isolation of ill patients. However,
      21% to 48% of LHDs lacked information of closure, absenteeism, or outbreaks in
      schools, and 28% to 50% lacked information on outpatient clinic capacity.
      CONCLUSIONS: Many LHDs were unable to monitor implementation of NPI (recommended
      by LHD or not) within their community during the 2009 H1N1 influenza pandemic.
      This gap makes it difficult to adjust recommendations or messaging during a
      public health emergency response. Public health preparedness could be improved by
      strengthening NPI monitoring capacity.

PMID- 23169407
TI  - The 1802 Saint-Domingue yellow fever epidemic and the Louisiana Purchase.
AB  - Epidemics have been pivotal in the history of the world as exemplified by a
      yellow fever epidemic in the Caribbean that clearly altered New World
      geopolitics. By the end of the 18th century, yellow fever--then an "emerging
      disease"--was widespread throughout the Caribbean and particularly lethal in
      Saint-Domingue (present day Haiti). From 1793 to 1798, case fatality rates among
      British troops in the West Indies (including Saint-Domingue) were as high as 70%.
      A worse fate befell newly arrived French armed forces in 1802, ostensibly sent by
      Napoleon to suppress a rebellion and to reestablish slavery. Historians have
      disagreed on why Napoleon initially dispatched nearly 30,000 soldiers and sailors
      to the island. Evidence suggests the troops were actually an expeditionary force
      with intensions to invade North America through New Orleans and to establish a
      major holding in the Mississippi valley. However, lacking knowledge of basic
      prevention and control measures, mortality from the disease left only a small and
      shattered fraction of his troops alive, thwarting his secret ambition to colonize
      and hold French-held lands, which later became better known as the Louisiana
      Purchase. If an event of the magnitude of France's experience were to occur in
      the 21st century, it might also have profound unanticipated consequences.

PMID- 23169408
TI  - A masterclass to teach public health professionals to conduct practice-based
      research to promote evidence-based practice: a case study from The Netherlands.
AB  - INTRODUCTION: Public health professionals have a pivotal position in efforts to
      obtain more practice-based evidence about what people need and what works in real
      circumstances. Close collaboration with researchers should enable public health
      professionals to design and conduct research in practical settings to address
      today's complex public health problems and increase the external validity of
      results. This requires expanding the research competencies of public health
      professionals. We developed and implemented a masterclass for public health
      professionals, modeled on an existing scientific training course for general
      practitioners and rehabilitation physicians. METHOD: The masterclass was
      evaluated using a multiple method design, involving quantitative and qualitative
      methods. Evaluation took place during, at the end of, and 9 months after the
      masterclass. RESULTS: Twenty-one candidates (mean age, 41 y) started the program,
      66% of whom completed it. Teaching materials, lectures, organization, and
      facilities were favorably evaluated. At the end of the masterclass, participants
      were able to design and implement a research proposal in their daily work
      setting, write a draft article, and critically appraise scientific research for
      practice and policy purposes. Participants had become more confident about their
      research competence. Management support from their employer proved crucial.
      Results obtained with the different methods were consistent. CONCLUSION: The
      masterclass appeared to be an effective instrument to increase the practice-based
      research skills of public health professionals, provided the research is
      implemented in a supportive organization with management backing and supervision
      by senior university researchers. We recommend using masterclasses to contribute
      to the improvement of practice-based evidence for projects addressing current and
      future public health problems.

PMID- 23169409
TI  - Strategies for public health in a transforming health system.

PMID- 23169410
TI  - Cross-sectoral workforce development:  examining the intersection of public
      health and community design.

PMID- 23169411
TI  - Succession planning and management in public health practice.

PMID- 23169412
TI  - Health and life concerns among patients attending a publicly funded sexually
      transmitted infection clinic.
AB  - OBJECTIVES: Sexually transmitted infection (STI) clinics provide opportune
      settings in which to address a range of health concerns with an underserved
      population. The current research sought to identify and prioritize patients'
      health and social concerns. DESIGN AND SETTING: Patients attending a publicly
      funded STI clinic (50% female, 62% African American) were invited to participate
      in a cross-sectional study. Participants completed a brief paper-and-pencil
      questionnaire. PARTICIPANTS: Participants were 150 patients attending the STI
      clinic. MAIN OUTCOME MEASURE: A survey of health and social concerns. RESULTS:
      Participants rated STIs, human immunodeficiency virus/AIDS, teeth problems, and
      eye problems as their most concerning health problems. Other than STI-related
      concerns, patients expressed few concerns about their somatic health. Instead,
      these (mostly younger) patients expressed more concern about economic issues.
      CONCLUSIONS: Sexually transmitted infection clinics provide a unique setting to
      provide health and mental health services to an at-need, underserved population;
      however, patients may prefer assistance with economic issues.

PMID- 23169413
TI  - Abortion surveillance--United States, 2009.
AB  - PROBLEM/CONDITION: Since 1969, CDC has conducted abortion surveillance to
      document the number and characteristics of women obtaining legal induced
      abortions in the United States. REPORTING PERIOD COVERED: 2009. DESCRIPTION OF
      SYSTEM: Each year, CDC requests abortion data from the central health agencies of
      52 reporting areas (the 50 states, the District of Columbia, and New York City).
      The reporting areas provide this information voluntarily. For 2009, data were
      received from 48 reporting areas. For the purpose of trend analysis, abortion
      data were evaluated from the 45 areas that reported data every year during 2000
      2009. Census and natality data, respectively, were used to calculated abortion
      rates (number of abortions per 1,000 women) and ratios (number of abortions per
      1,000 live births). RESULTS: A total of 784,507 abortions were reported to CDC
      for 2009. Of these abortions, 772,630 (98.5%) were from the 45 reporting areas
      that provided data every year during 2000-2009. Among these same 45 reporting
      areas, the abortion rate for 2009 was 15.1 abortions per 1,000 women aged 15-44
      years, and the abortion ratio was 227 abortions per 1,000 live births. Compared
      with 2008, the total number and rate of reported abortions for 2009 decreased 5%,
      representing the largest single year decrease for the entire period of analysis.
      The abortion ratio decreased 2%. From 2000 to 2009, the total number, rate, and
      ratio of reported abortions decreased 6%, 7%, and 8%, respectively, to the lowest
      levels for 2000-2009. In 2009 and throughout the period of analysis, women in
      their 20s accounted for the majority of abortions and had the highest abortion
      rates, whereas women aged >=30 years accounted for a much smaller percentage of
      abortions and had lower abortion rates. In 2009, women aged 20-24 and 25-29 years
      accounted for 32.7% and 24.4% of all abortions, respectively, and had an abortion
      rate of 27.4 abortions per 1,000 women aged 20-24 years and 20.4 abortions per
      1,000 women aged 25-29 years. In contrast, women aged 30-34, 35-39, and >=40
      years accounted for 14.7%, 8.8%, and 3.3% of all abortions, respectively, and had
      an abortion rate of 13.3 abortions per 1,000 women aged 30-34 years, 7.6
      abortions per 1,000 women aged 35-39 years, and 2.7 abortions per 1,000 women
      aged >=40 years. Throughout the period of analysis, abortion rates decreased
      among women aged 20-24 and 25-29 years, whereas they increased among women aged
      >=40 years. In 2009, adolescents aged 15-19 years accounted for 15.5% of all
      abortions and had an abortion rate of 13.0 abortions per 1,000 adolescents aged
      15-19 years. Throughout the period of analysis, the percentage of all abortions
      accounted for by adolescents and the adolescent abortion rate decreased. In
      contrast to the percentage distribution of abortions and abortion rates by age,
      abortion ratios in 2009 and throughout the entire period of analysis were highest
      among adolescents and lowest among women aged 30-39 years. Abortion ratios
      decreased from 2000 to 2009 for women in all age groups except for those aged <15
      years, for whom they increased. In 2009, most (64.0%) abortions were performed at
      <=8 weeks' gestation, and 91.7% were performed at <=13 weeks' gestation. Few
      abortions (7.0%) were performed at 14-20 weeks' gestation, and even fewer (1.3%)
      were performed at >=21 weeks' gestation. From 2000 to 2009, the percentage of all
      abortions performed at <=8 weeks' gestation increased 12%, whereas the percentage
      performed at >13 weeks' decreased 12%. Moreover, among abortions performed at
      <=13 weeks' gestation, the distribution shifted toward earlier gestational ages,
      with the percentage of these abortions performed at <=6 weeks' gestation
      increasing 47%. In 2009, 74.2% of abortions were performed by curettage at <=13
      weeks' gestation, 16.5% were performed by early medical abortion (a nonsurgical
      abortion at <=8 weeks' gestation), and 8.1% were performed by curettage at >13
      weeks' gestation. Among abortions that were performed at <=8 weeks' gestation and
      thus were eligible for early medical abortion, 25.2% were completed by this
      method. The use of early medical abortion increased 10% from 2008 to 2009. Deaths
      of women associated with complications from abortions for 2009 are being
      investigated under CDC's Pregnancy Mortality Surveillance System. In 2008, the
      most recent year for which data were available, 12 women were reported to have
      died as a result of complications from known legal induced abortions. No reported
      deaths were associated with known illegal induced abortions. INTERPRETATION:
      Among the 45 areas that reported data every year during 2000-2009, the gradual
      decrease that had occurred during previous decades in the total number and rate
      of reported abortions continued through 2005, whereas year-to-year variation from
      2006 to 2008 resulted in no net change during this later period. However, the
      change from 2008 to 2009 for both the total number of abortions and the abortion
      rate was the largest single year decrease during 2000-2009, and all three
      measures of abortion (total numbers, rates, and ratios) decreased to the lowest
      level observed during this period. PUBLIC HEALTH ACTIONS: Unintended pregnancy is
      the major contributor to abortion. Because unintended pregnancies are rare among
      women who use the most effective methods of reversible contraception, increasing
      access to and use of these methods can help further reduce the number of
      abortions performed in the United States. The data in this report can help
      program planners and policy makers identify groups of women at greatest risk for
      unintended pregnancy and help guide and evaluate prevention efforts.

PMID- 23169415
TI  - Infections in dermatopathology:  emerging frontiers.
AB  - Significant difficulties continue to exist in the diagnosis of many infectious
      diseases in dermatopathology. Identifying pathogens in skin biopsies using
      conventional diagnostic techniques such as microscopy and tissue culture has its
      limitations. In recent times, molecular techniques including
      immunohistochemistry, polymerase chain reaction, and in situ hybridization have
      emerged as useful tools in the diagnosis of cutaneous infections that are
      challenging and ambiguous on conventional histopathology, thus improving our
      diagnostic accuracy. In this review, we highlight the main molecular techniques
      that have been used and continue to evolve in the diagnosis of mucocutaneous
      infectious diseases and discuss their applicability.

PMID- 23169416
TI  - Microvenular hemangioma-an immunohistochemical study of 9 cases.
AB  - Microvenular hemangioma (MH) is a rare benign acquired vascular neoplasm, which
      can be clinically and histologically misdiagnosed with other vascular lesions.
      Immunohistochemistry studies in MH are lacking. The aim of this study is to
      investigate the immunoprofile of MH and gain further insight in its histogenesis.
      We evaluated 9 cases of MH. Immunohistochemical expression of WT1, GLUT-1, and D2
      40 was performed in all cases. All 9 MHs resulted completely positive for WT1
      immunostaining. Immunohistochemistry performed in all 9 MH cases showed negative
      staining for GLUT-1 and D2-40. We added further support to the importance of WT1
      as a useful tool in the diagnosis of vascular neoplasms. D2-40 negativity in all
      tested lesions implied that MH does not exhibit a lymphatic differentiation. GLUT
      1, which is characteristically positive in infantile hemangioma and verrucous
      hemangioma, showed to be negative in MHs.

PMID- 23169417
TI  - Infantile donovanosis presenting as external auditory canal polyps:  a diagnostic
      trap.
AB  - Two infants, 6 months and 4 months of age, presented with bilateral or unilateral
      external auditory canal polyps and otorrhea, respectively. Additional findings on
      examination included otitis media and mastoiditis. Tympanic membrane perforation
      was noted in one patient and a postauricular abscess in the other. Incisional
      biopsies of the polyps and abscess were reported as nonspecific mixed
      inflammation and abscess wall, respectively. There was a limited response to an
      empirical 5-day course of trimethoprim sulfamethoxazole. The children were
      referred to the academic hospital, and excision of the polyps and biopsies of the
      middle ear, mastoid, and postauricular abscess was undertaken. All the biopsies
      demonstrated donovanosis. Reappraisal of the initial incisional biopsies also
      confirmed donovanosis. Trimethoprim sulfamethoxazole was administered to both
      patients for 3 weeks, with resolution of the lesions. Subsequent investigations
      confirmed genital tract donovanosis, human immunodeficiency virus seropositivity,
      acquired immunodeficiency syndrome, and pulmonary tuberculosis in both mothers.
      Heightened awareness of the occurrence of donovanosis at unusual sites and
      improved recognition of the histomorphological features of the disease,
      especially in small and superficial biopsies, are pivotal not only for its
      correct diagnosis in extragenital cutaneous and extracutaneous locations but also
      for timely and adequate therapy and an improved infant and maternal outcome.

PMID- 23169418
TI  - Minocycline-induced hyperpigmentation in multibacillary leprosy.
AB  - Minocycline has been used in the treatment of leprosy since the demonstration of
      its efficacy in inhibiting Mycobacterium leprae growth in 1987.
      Hyperpigmentation, a well-documented adverse effect, classically shows 3 clinical
      and histological patterns: type I consists of blue-black pigmentation in areas of
      current or previous inflammation, type II consists of blue-gray pigmentation of
      normal skin, often seen on the legs, and type III consists of diffuse muddy-brown
      pigmentation accentuated on sun-exposed sites. Whereas type I hyperpigmentation
      stains positively for hemosiderin and type III hyperpigmentation stains
      positively for melanin, type II hyperpigmentation stains positively for both. We
      describe 2 patients with leprosy on minocycline therapy who developed multiple
      patches of blue-gray pigmentation within preexisting leprosy lesions. Biopsies
      from both patients demonstrated deposition of brownish-black pigment granules
      within the cytoplasm of foamy histiocytes that was highlighted by both Perls and
      Fontana-Masson stains. Given the clinical and histological findings in our
      patients, it is as yet unclear whether this coexistent type I clinical pattern
      and type II histopathologic pattern of pigmentation is unique to multibacillary
      leprosy. These findings provide support for the existence of additional subtypes
      of minocycline-induced hyperpigmentation that do not adhere to the classic 3-type
      model described.

PMID- 23169420
TI  - Chondroid syringoma with marked calcification.
AB  - Chondroid syringoma is an uncommon benign neoplasm in the skin. It is composed of
      epithelial and myoepithelial cells embedded in a matrix with varying amounts of
      mucoid and cartilaginous material. Chondroid syringoma is classified into 2
      types, the apocine type and the eccrine type. Several cases of the eccrine type
      chondroid syringoma with ossification and calcification have been reported, but
      the apocrine type chondroid syringoma with calcification has not been reported.
      In this report, we describe a case of apocrine type chondroid syringoma with
      calcification.

PMID- 23169419
TI  - Atypical hydroa vacciniforme-like epstein-barr virus associated T/NK-cell
      lymphoproliferative disorder.
AB  - Epstein-Barr virus (EBV)-associated T-cell/natural killer (NK)-cell
      lymphoproliferative disorders (EBV-T/NK-LPDs) accompany severe chronic active EBV
      infection (CAEBV) or comprise the CAEBV disease entity. The CAEBV disease entity
      has the common feature of lymphoproliferation of T or NK cells (primarily), and B
      cells (rarely), with chronic activation of EBV infection. The disease is rare and
      seems to be more prevalent in East Asian countries. The CAEBV disease entity
      encompasses heterogenous disorders, including hydroa vacciniforme (HV),
      hypersensitivity to mosquito bites, EBV-associated hemophagocytic syndrome, NK/T
      cell lymphoma, and NK-cell leukemia. Atypical HV-like eruptions are present on
      sun-exposed and nonexposed areas with facial edema, fever, and
      hepatosplenomegaly, unlike classic HV. Recently, it has been suggested that
      classic HV and atypical HV-like eruptions are variants within the same disease
      spectrum of EBV-T/NK-LPD. We report a Korean boy with an atypical HV-like
      eruption and various systemic manifestations, including fever, sore throat,
      abdominal pain, headaches, seizures, and hematologic abnormalities for 2 years.
      After the initial mild eruption, which resembled a viral exanthem, ulceronecrotic
      skin lesions gradually developed and were associated with a high-grade fever and
      constitutional symptoms. He had a CAEBV infection, which showed a predominant
      proliferation of NK cells with high EBV DNA levels in the peripheral blood.
      However, in the skin lesions, there were nonneoplastic CD4 T-cell infiltrations
      predominantly showing a monoclonal T-cell receptor-gamma gene rearrangement and
      positive EBV in situ hybridization.

PMID- 23169421
TI  - Acral pseudolymphomatous angiokeratoma of children:  a case report with
      immunohistochemical study of antipodoplanin antigen.
AB  - Acral pseudolymphomatous angiokeratoma of children (APACHE) is characterized by
      multiple angiomatous papules on the hands and feet in children. Here, we report a
      case of APACHE in a female patient followed up from 13 to 19 years of age with a
      dark red lesion on the center of the dorsum of the right thigh. Histologically,
      vacuolar alteration and exocytosis of lymphocytes, and specific dense cellular
      infiltration beneath the epidermis to the reticular dermis were found. On
      immunolabeling study, the lesion vessels were found to be positive for both the
      lymphatic endothelium-specific marker podoplanin and blood vessel-specific marker
      CD34. These findings suggested that APACHE is a type of vascular malformation.

PMID- 23169427
TI  - Liver transplantation and transthyretin amyloidosis.
AB  - Liver transplantation as a specific treatment of transthyretin amyloidosis was
      first performed in 1990. The rationale for this treatment was that removal of the
      source (liver) of the amyloid precursor protein (mutated transthyretin) would
      stop progression of the disease. Indeed, after orthotopic liver transplantation
      (OLT), mutant transthyretin (TTR) is rapidly cleared from circulation. In the
      last 20 years, >2000 familial amyloidotic polyneuropathy (FAP) patients have
      received liver transplants. For these patients, prospective monitoring has shown
      prolongation of life compared with FAP patients who have not undergone liver
      transplantation. The most favorable results have been for FAP patients with the
      Val30Met TTR mutation. Less favorable results have been seen for patients with
      other TTR mutations where progression of amyloid tissue deposition has been
      documented as the result of amyloid fibril formation from normal (wild-type) TTR.
      Although it is obvious that OLT has benefited many FAP patients, there remains a
      need for further therapies.

PMID- 23169428
TI  - Probing the nature of the cluster effect observed with synthetic multivalent
      galactosides and peanut agglutinin lectin.
AB  - We designed a set of multi-galactosides with valencies ranging from one to seven
      and different spacer-arm lengths. The compounds display a high structural
      homology for a strict assessment of multivalent phenomena. The multimers were
      first evaluated by an enzyme-linked lectin assay (ELLA) toward the peanut
      agglutinin (PNA). The binding affinity was shown to be dependent on the spacer
      arm length, and cluster effects were observed for the galactosides bearing the
      shortest and the longest linkers. The latter compounds were shown to be much more
      potent PNA cross-linkers in a "sandwich assay". Dynamic light scattering (DLS)
      experiments also revealed the formation of soluble aggregates between heptavalent
      derivatives with medium or long linkers and the labeled PNA. ELLA experiments
      performed with valency-controlled clusters and labeled lectins are therefore not
      always devoid from aggregative processes. The precise nature of the multivalent
      interaction observed by ELLA for the compounds bearing the shortest linkers,
      which are unable to form PNA aggregates, was further investigated by atomic force
      microscopy (AFM). The galactosides were grafted onto the tip of a cantilever and
      the PNA lectin onto a gold surface. Similar unbinding forces were registered when
      the valency of the ligands was increased, thus showing that the multimers cannot
      interact more strongly with PNA. Multiple binding events to the PNA were also
      never observed, thus confirming that a chelate binding mode does not operate with
      the multivalent galactosides, probably because the linkers are too short.
      Altogether, these results suggest that the cluster effect that operates in ELLA
      with the multimers is not related to additional PNA stabilizations and can be
      ascribed to local concentration effects that favor a dynamic turnover of the
      tethered galactosides in the PNA binding sites.

PMID- 23169429
TI  - Simultaneous inference for several quantiles of a normal population with
      applications.
AB  - A common statistical problem is to make inference about the mean of a normally
      distributed population. While the mean and the variance are important quantities,
      many real problems require information on certain quantiles of the population
      which combine both the mean and variance. Motivated by two recent applications,
      we consider simultaneous inference for more than one quantile of interest. In
      this paper, a set of exact 1-alpha level simultaneous confidence intervals for
      several quantiles of a normally distributed population is constructed, based on a
      simple random sample from that population. The critical constants for achieving
      an exact 1-alpha simultaneous coverage probability can be computed efficiently
      using numerical quadrature involving only a one-dimensional integral combined
      with standard search algorithms. The proposed methods are illustrated with an
      example. Several further research problems are identified.

PMID- 23169430
TI  - Drug interactions produced by proton pump inhibitors: not simply a pH effect.

PMID- 23169431
TI  - Physiologically based pharmacokinetic modeling at the extremes of age.

PMID- 23169432
TI  - Response to "Drug interactions produced by proton pump inhibitors: not simply a
      pH effect".

PMID- 23169433
TI  - Resistance training in patients with limb-girdle and becker muscular dystrophies.
AB  - INTRODUCTION: In this study we investigated the effect of strength training in
      patients with limb-girdle muscular dystrophy (LGMD) and Becker muscular dystrophy
      (BMD). METHODS: In 2 studies we compared the effect of low-intensity training
      (LOIT; n = 8) and high-intensity training (HIT; n = 4) in muscles of the upper
      and lower extremities. Patients were tested for maximal strength and endurance
      before and after the training program. RESULTS: LOIT training over 6 months
      resulted in increased biceps strength and endurance. HIT training increased
      endurance and strength in wrist flexion and extension and in elbow flexion. One
      patient discontinued HIT training due to muscle soreness and mildly increased
      plasma CK levels without strength deterioration. CONCLUSIONS: Both LOIT and HIT
      increased muscle strength and endurance in some of the muscles tested and were
      well tolerated in most patients. Our findings suggest that supervised resistance
      training may be considered in the management of patients with LGMD2 and BMD.

PMID- 23169434
TI  - Speech rehabilitation during the first year after total laryngectomy.
AB  - BACKGROUND: Gaining a new voice is one of the major aims after total
      laryngectomy. The objective of this study was to describe the process and results
      of speech rehabilitation during the first year after surgery. METHODS: Speech
      intelligibility was measured 6 months (n = 273) and 1 year (n = 225) after total
      laryngectomy. RESULTS: Objective (23.4 to 47.5 points, p < .0001) and subjective
      (51.6 to 64.7 points, p < .0001) speech intelligibility improved between 6 months
      and 1 year after total laryngectomy. Patients who used tracheoesophageal puncture
      (TEP) had the best results in speech intelligibility 6 months and 1 year after
      total laryngectomy. In all, 12% of the patients who used TEP initially no longer
      used it 1 year later. Patients who had received rehabilitation had better
      objective speech intelligibility than those who did not. CONCLUSIONS: Speech
      improves considerably between 6 months and 1 year after total laryngectomy.
      Nonattendance of rehabilitation is associated with a worse functional outcome in
      speech rehabilitation.

PMID- 23169435
TI  - Predictive impact of circulating vascular endothelial growth factor in four phase
      III trials evaluating bevacizumab.
AB  - PURPOSE: We evaluated the prognostic and predictive use of circulating VEGF-A
      levels in phase III trials of bevacizumab in colorectal cancer, lung cancer, and
      renal cell carcinoma. METHODS: Baseline plasma samples from 1,816 patients were
      analyzed for VEGF-A using an ELISA, which recognizes the major isoforms with
      equivalent sensitivity. HR and 95% confidence intervals (CI) for study end points
      were estimated using Cox regression analysis. A subset of matched archival tumor
      samples was analyzed for VEGF-A expression using in situ hybridization. RESULTS:
      Higher VEGF-A levels showed trends toward adverse prognostic significance in the
      control arms of multiple trials, reaching statistical significance for overall
      survival (OS) in AVF2107 (highest vs. lowest 50%: HR = 1.76; 95% CI, 1.28-2.41),
      AVAiL (HR = 1.52; 95% CI, 1.16-2.00), and AVOREN (HR = 1.67; 95% CI, 1.18-2.36).
      In predictive analyses, the HRs for progression-free survival were similar across
      low and high VEGF-A subgroups and favored bevacizumab-containing treatment. In
      the low VEGF-A subgroups, HRs (95% CIs) were 0.61 (0.43-0.87) in AVF2107, 0.71
      (0.43-1.16) in E4599, 0.74 (0.59-0.94) in AVAiL (low-dose), 0.89 (0.70-1.13) in
      AVAiL (high-dose), and 0.56 (0.40-0.78) in AVOREN. Analyses of OS data have shown
      similar results. No correlation between primary tumor VEGF-A expression and
      plasma VEGF-A levels was observed. CONCLUSIONS: In this comprehensive evaluation,
      pretreatment total circulating VEGF-A was prognostic for outcome in metastatic
      colorectal, lung, and renal cell cancers, but it was not predictive for
      bevacizumab-based treatment benefit.

PMID- 23169436
TI  - Durable cancer regression off-treatment and effective reinduction therapy with an
      anti-PD-1 antibody.
AB  - PURPOSE: Results from the first-in-human phase I trial of the anti-programmed
      death-1 (PD-1) antibody BMS-936558 in patients with treatment-refractory solid
      tumors, including safety, tolerability, pharmacodynamics, and immunologic
      correlates, have been previously reported. Here, we provide long-term follow-up
      on three patients from that trial who sustained objective tumor regressions off
      therapy, and test the hypothesis that reinduction therapy for late tumor
      recurrence can be effective. EXPERIMENTAL DESIGN: Three patients with colorectal
      cancer, renal cell cancer, and melanoma achieved objective responses on an
      intermittent dosing regimen of BMS-936558. Following cessation of therapy,
      patients were followed for more than 3 years. A patient with melanoma who
      experienced a prolonged partial regression followed by tumor recurrence received
      reinduction therapy. RESULTS: A patient with colorectal cancer experienced a
      complete response, which is ongoing after 3 years. A patient with renal cell
      cancer experienced a partial response lasting 3 years off therapy, which
      converted to a complete response, which is ongoing at 12 months. A patient with
      melanoma achieved a partial response that was stable for 16 months off therapy;
      recurrent disease was successfully treated with reinduction anti-PD-1 therapy.
      CONCLUSION: These data represent the most prolonged observation to date of
      patients with solid tumors responding to anti-PD-1 immunotherapy and the first
      report of successful reinduction therapy following delayed tumor progression.
      They underscore the potential for immune checkpoint blockade with anti-PD-1 to
      reset the equilibrium between tumor and the host immune system.

PMID- 23169438
TI  - Clinicopathologic features of V600E and V600K melanoma--letter.

PMID- 23169439
TI  - Synthesis of a new pH-sensitive folate-doxorubicin conjugate and its antitumor
      activity in vitro.
AB  - Folate-aminocaproic acid-doxorubicin (FA-AMA-DOX) was synthesized and
      characterized by H NMR spectroscopy and mass spectrometry. Cytotoxicity and
      cellular uptake experiments were performed in KB and HepG2 cells, which express
      folic acid receptor, and the cell line A549, which does not express folic acid
      receptor. Cytotoxicity was determined using the 3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide assay, and cellular uptake was monitored using
      fluorescence microscopy. The amount of DOX released from FA-AMA-DOX was much
      greater at pH 5.0 than that at pH 6.5 or 7.4. The cytotoxicity of FA-AMA-DOX
      toward KB and HepG2 cells was greater than that of DOX or AMA-DOX at the same
      concentrations, and cytotoxicity could be attenuated by FA in a dose-dependent
      manner. On the contrary, the cytotoxicity of FA-AMA-DOX and AMA-DOX toward A549
      cells was lower than that of DOX at the same concentration, and cytotoxicity
      could not be reduced by FA. Compared with FA-AMA, FA-AMA-DOX increased the
      intracellular accumulation of DOX in KB cells. These results suggested that FA
      AMA-DOX have suitable attributes for the active targeting of folate-receptor
      positive tumor cells and for releasing the chemotherapeutic agent, DOX, in situ;
      it therefore has potential as a novel cancer therapeutic.

PMID- 23169441
TI  - Bioinspired, releasable quorum sensing modulators.
AB  - We demonstrate the synthesis and immobilization of natural product hybrids
      featuring an acyl-homoserine lactone and a nitrodopamine onto biocompatible
      TiO(2) surfaces through an operationally simple dip-and-rinse procedure. The
      resulting immobilized hybrids were shown to be powerful quorum sensing (QS)
      activators in Pseudomonas strains acting by slow release from the surface.

PMID- 23169442
TI  - Recombinant proteins as cross-linkers for hydrogelations.
AB  - Protein-based hydrogels are promising materials for tissue engineering and drug
      delivery due to the unique properties of proteins such as perfect polydispersity,
      exact control over monomer sequence, ability to fine-tune molecular-level
      biochemical interactions, etc. This tutorial review summarizes recent progress on
      the preparation of protein-based hydrogels and their applications. Typically, we
      introduce two strategies of covalent and non-covalent ones for the preparation of
      hydrogels. Hydrogels prepared by the covalent strategy are stable and can respond
      to the conformational change of proteins. They can be applied for cells
      encapsulation, screening of drug molecules and heavy metals, etc. Hydrogels
      formed by non-covalent interactions are injectable physical hydrogels. The simple
      mixing preparation strategy and fast gelation kinetics guarantee the homogeneous
      encapsulation of cells and therapeutic agents within them. Therefore, they have
      been widely applied for the delivery of bioactive components, regenerative
      medicine, etc. The challenges that remained in this field are also summarized in
      this paper. We envision that rationally designed protein-based hydrogels will
      have broad applications in many areas including controlled delivery, tissue
      engineering, drug screening, etc.

PMID- 23169440
TI  - The vagus nerve and the inflammatory reflex--linking immunity and metabolism.
AB  - The vagus nerve has an important role in regulation of metabolic homeostasis, and
      efferent vagus nerve-mediated cholinergic signalling controls immune function and
      proinflammatory responses via the inflammatory reflex. Dysregulation of
      metabolism and immune function in obesity are associated with chronic
      inflammation, a critical step in the pathogenesis of insulin resistance and type
      2 diabetes mellitus. Cholinergic mechanisms within the inflammatory reflex have,
      in the past 2 years, been implicated in attenuating obesity-related inflammation
      and metabolic complications. This knowledge has led to the exploration of novel
      therapeutic approaches in the treatment of obesity-related disorders.

PMID- 23169443
TI  - Mitogen-activated protein kinase 2 regulates physiological and pathological bone
      turnover.
AB  - The objective of this study was to investigate the role of the serine-threonine
      kinase mitogen-activated protein kinase 2 (MK2) in bone homeostasis. Primary bone
      cell cultures from MK2(+/+) and MK2(-/-) mice were assessed for osteoclast and
      osteoblast differentiation, bone resorption, and gene expression. Bone
      architecture of MK2(+/+) and MK2(-/-) mice was investigated by micro-computed
      tomography and histomorphometry. Ovariectomy was performed in MK2(+/+) and MK2(-/
      ) mice to assess the role of MK2 in postmenopausal bone loss. Osteoclastogenesis,
      bone resorption, and osteoclast gene expression were significantly impaired in
      monocytes from MK2(-/-) compared to MK2(+/+) mice. Mechanistically, loss of MK2
      causes impaired DNA binding of c-fos and nuclear factor of activated T cells
      cytoplasmic 1 (NFATc1) to tartrate-resistant acid phosphatase (TRAP) and the
      calcitonin receptor gene promoter. In addition, MK2(-/-) mice showed an age
      dependent increase in trabecular bone mass and cortical thickness, fewer
      osteoclasts, and lower markers of bone resorption than MK2(+/+) mice.
      Furthermore, MK2(-/-) mice were protected from ovariectomy-induced bone loss.
      Osteoblastogenesis and bone formation were unchanged in MK2(-/-) mice, whereas
      osteoblast expression of osteoprotegerin (OPG) and serum levels of OPG were
      higher in MK2(-/-) than in MK2(+/+) mice. Loss of MK2 effectively blocks bone
      resorption and prevents the development of postmenopausal bone loss. Small
      molecule inhibitors of MK2 could thus emerge as highly effective tools to block
      bone resorption and to treat postmenopausal bone loss.

PMID- 23169445
TI  - Monitoring of ubiquitin-proteasome activity in living cells using a Degron (dgn)
      destabilized green fluorescent protein (GFP)-based reporter protein.
AB  - Proteasome is the main intracellular organelle involved in the proteolytic
      degradation of abnormal, misfolded, damaged or oxidized proteins (1, 2).
      Maintenance of proteasome activity was implicated in many key cellular processes,
      like cell's stress response (3), cell cycle regulation and cellular
      differentiation (4) or in immune system response (5). The dysfunction of the
      ubiquitin-proteasome system has been related to the development of tumors and
      neurodegenerative diseases (4, 6). Additionally, a decrease in proteasome
      activity was found as a feature of cellular senescence and organismal aging (7,
      8, 9, 10). Here, we present a method to measure ubiquitin-proteasome activity in
      living cells using a GFP-dgn fusion protein. To be able to monitor ubiquitin
      proteasome activity in living primary cells, complementary DNA constructs coding
      for a green fluorescent protein (GFP)-dgn fusion protein (GFP-dgn, unstable) and
      a variant carrying a frameshift mutation (GFP-dgnFS, stable (11)) are inserted in
      lentiviral expression vectors. We prefer this technique over traditional
      transfection techniques because it guarantees a very high transfection efficiency
      independent of the cell type or the age of the donor. The difference between
      fluorescence displayed by the GFP-dgnFS (stable) protein and the destabilized
      protein (GFP-dgn) in the absence or presence of proteasome inhibitor can be used
      to estimate ubiquitin-proteasome activity in each particular cell strain. These
      differences can be monitored by epifluorescence microscopy or can be measured by
      flow cytometry.

PMID- 23169447
TI  - Guidelines for reporting and using prediction tools for genetic variation
      analysis.
AB  - Computational prediction methods are widely used for the analysis of human genome
      sequence variants and their effects on gene/protein function, splice site
      aberration, pathogenicity, and disease risk. New methods are frequently
      developed. We believe that guidelines are essential for those writing articles
      about new prediction methods, as well as for those applying these tools in their
      research, so that the necessary details are reported. This will enable readers to
      gain the full picture of technical information, performance, and interpretation
      of results, and to facilitate comparisons of related methods. Here, we provide
      instructions on how to describe new methods, report datasets, and assess the
      performance of predictive tools. We also discuss what details of predictor
      implementation are essential for authors to understand. Similarly, these
      guidelines for the use of predictors provide instructions on what needs to be
      delineated in the text, as well as how researchers can avoid unwarranted
      conclusions. They are applicable to most prediction methods currently utilized.
      By applying these guidelines, authors will help reviewers, editors, and readers
      to more fully comprehend prediction methods and their use.

PMID- 23169446
TI  - Inhibition of human MDR1 and BCRP transporter ATPase activity by organochlorine
      and pyrethroid insecticides.
AB  - Despite the growing evidence suggesting that pesticides contribute to chronic
      diseases, there is a limited understanding of how these chemicals are removed
      from cells and whether pesticides can alter the disposition of drugs. The present
      study examined the effects of two classes of insecticides (organochlorine and
      pyrethroid) on the ATPase activity of the human multidrug resistance protein 1
      (MDR1) and breast cancer resistance protein (BCRP) efflux transporters. Using
      plasma membranes from cells overexpressing MDR1 and BCRP, it was demonstrated
      that the organochlorine pesticide dichlorodiphenyltrichloroethane (DDT) (o,p'-DDT
      and p,p'-DDT isomers) as well as its metabolite (p,p'
      dichlorodiphenyldichloroethane), inhibit both MDR1 and BCRP ATPase activity. In
      addition, p,p'-dichlorodiphenyldichloroethylene, and two pyrethroid pesticides
      inhibited BCRP ATPase activity between 4 and 7 MUM. Additional research is
      necessary to further characterize the functional inhibition of MDR1 and BCRP
      activity and determine whether pesticides alter the transporter-mediated
      disposition of other chemicals.

PMID- 23169448
TI  - Activated leukocyte cell adhesion molecule soluble form: a potential biomarker of
      epithelial ovarian cancer is increased in type II tumors.
AB  - Activated leukocyte cell adhesion molecule (ALCAM) is involved in cell-cell
      interactions in cancer. Shedding of its ectodomain by the metalloprotease
      ADAM17/TACE generates a soluble form (sALCAM). Here, we show that serum sALCAM
      levels were significantly higher in epithelial ovarian cancer (EOC) (p < 0.005)
      than in controls. The performance of sALCAM as classifier, tested by receiver
      operating characteristic curve, resulted in an area under the curve (AUC) of
      0.8067. Serum sALCAM levels showed direct correlation with Carbohydrate Antigen
      125 (CA125/MUC16). Moreover, significantly higher levels were found in type II
      tumors, even in stage I/II, suggesting that elevated sALCAM is an early feature
      of aggressive EOC. In addition, sALCAM levels were higher in ascites than in
      sera, suggesting local processing of ALCAM in the peritoneal cavity. In
      immunodeficient mice, intraperitoneally implanted with a human EOC cell line,
      human sALCAM progressively increased in serum and was even higher in the ascites.
      The biochemical characterization of the sALCAM in EOC sera and ascites, showed
      two predominant forms of approximately 95 and 65 kDa but no EOC-specific isoform.
      In addition, full-length transmembrane ALCAM but no soluble form was detected in
      tumor-derived exosomes found in ascites. Finally, in vitro invasion assays showed
      that inhibition of ADAM17/TACE activity decreased EOC invasive properties, while
      opposite effects were mediated by a sALCAM-Fc chimera and by an antibody
      interfering with ALCAM/ALCAM interactions. Altogether these data suggest that
      sALCAM is a marker of EOC, which correlates with more aggressive type II tumors,
      and that ADAM17/TACE activity and sALCAM itself mediate enhanced invasiveness.

PMID- 23169449
TI  - [Rh(III)(dmbpy)2Cl2]+ as a highly efficient catalyst for visible-light-driven
      hydrogen production in pure water: comparison with other rhodium catalysts.
AB  - We report a very efficient homogeneous system for the visible-light-driven
      hydrogen production in pure aqueous solution at room temperature. This comprises
      [Rh(III) (dmbpy)(2)Cl(2)]Cl (1) as catalyst, [Ru(bpy)(3)]Cl(2) (PS1) as
      photosensitizer, and ascorbate as sacrificial electron donor. Comparative studies
      in aqueous solutions also performed with other known rhodium catalysts, or with
      an iridium photosensitizer, show that 1) the PS1/1/ascorbate/ascorbic acid system
      is by far the most active rhodium-based homogeneous photocatalytic system for
      hydrogen production in a purely aqueous medium when compared to the previously
      reported rhodium catalysts, Na(3)[Rh(I) (dpm)(3)Cl] and
      [Rh(III)(bpy)Cp*(H(2)O)]SO(4) and 2) the system is less efficient when [Ir(III)
      (ppy)(2)(bpy)]Cl(PS2) is used as photosensitizer. Because catalyst 1 is the most
      efficient rhodium-based H(2)-evolving catalyst in water, the performance limits
      of this complex were further investigated by varying the PS1/1 ratio at pH 4.0.
      Under optimal conditions, the system gives up to 1010 turnovers versus the
      catalyst with an initial turnover frequency as high as 857 TON h(-1). Nanosecond
      transient absorption spectroscopy measurements show that the initial step of the
      photocatalytic H(2)-evolution mechanism is a reductive quenching of the PS1
      excited state by ascorbate, leading to the reduced form of PS1, which is then
      able to reduce [Rh(III)(dmbpy)(2)Cl(2)](+) to [Rh(I)(dmbpy)(2)](+). This reduced
      species can react with protons to yield the hydride
      [Rh(III)(H)(dmbpy)(2)(H(2)O)](2+), which is the key intermediate for the H(2)
      production.

PMID- 23169450
TI  - Continuous intraoperative vagus nerve stimulation for identification of imminent
      recurrent laryngeal nerve injury.
AB  - BACKGROUND: Conventional intraoperative nerve monitoring, predicated on
      intermittent stimulation, can predict recurrent laryngeal nerve (RLN) palsy only
      after the damage has been done. METHODS: Fifty-two patients (52 nerves at risk)
      who underwent continuous intraoperative nerve monitoring (CIONM) for thyroid
      surgery via vagus nerve stimulation had their electromyographic (EMG) tracings
      recorded and correlated with surgical maneuvers and postoperative RLN function.
      RESULTS: There was 1 imminent loss of signal (LOS) with intraoperative signal
      recovery and there were 4 losses of signal with corresponding unilateral
      transient RLN palsy. When EMG amplitude decreased >50% and EMG latency increased
      >10%, LOS and postoperative RLN palsy were noted in 4 of 8 patients (50%) who had
      multiple combined events. In 9 of 13 patients (70%) who developed adverse EMG
      changes, modification of the causative surgical maneuver resulted in recovery of
      those EMG changes and aversion of impending RLN palsy. CONCLUSION: CIONM reliably
      signaled impending nerve injury, enabling immediate corrective action.

PMID- 23169451
TI  - A progressive translational mouse model of human valosin-containing protein
      disease: the VCP(R155H/+) mouse.
AB  - INTRODUCTION: Mutations in the valosin-containing protein (VCP) gene cause
      hereditary inclusion body myopathy (IBM) associated with Paget disease of bone
      (PDB), and frontotemporal dementia (FTD). More recently, these mutations have
      been linked to 2% of familial amyotrophic lateral sclerosis (ALS) cases. A knock
      in mouse model offers the opportunity to study VCP-associated pathogenesis.
      METHODS: The VCP(R155H/+) knock-in mouse model was assessed for muscle strength
      and immunohistochemical, Western blot, apoptosis, autophagy, and microPET/CT
      imaging analyses. RESULTS: VCP(R155H/+) mice developed significant progressive
      muscle weakness, and the quadriceps and brain developed progressive cytoplasmic
      accumulation of TDP-43, ubiquitin-positive inclusion bodies, and increased LC3-II
      staining. MicroCT analyses revealed Paget-like lesions at the ends of long bones.
      Spinal cord demonstrated neurodegenerative changes, ubiquitin, and TDP-43
      pathology of motor neurons. CONCLUSIONS: VCP(R155H/+) knock-in mice represent an
      excellent preclinical model for understanding VCP-associated disease mechanisms
      and future treatments.

PMID- 23169453
TI  - It's not just leukocytes in cytometry.

PMID- 23169452
TI  - Clinical evolution of pure upper motor neuron disease/dysfunction (PUMMD).
AB  - INTRODUCTION: PLS is defined as pure upper motor neuron disease/dysfunction
      (PUMND) beyond 48 months after symptom onset. We know little about its early
      stages, but such knowledge would help to identify the mechanisms underlying PLS
      and ALS and determine why PLS patients seem to be protected against lower MND
      (LMND). METHODS: We reviewed 622 MND cases during a 4-year period and identified
      34 patients with PUMND (5.4%). RESULTS: Among 23 cases with follow-up
      data/electromyograms (EMGs; 2 had only 1 EMG), 13 (57%) remained classified as
      PUMND, and 8 (35%) developed LMND (mean, 51.4 months after onset). Of these 8,
      LMND developed in 3 after 48 months from symptom onset. Patients with PUMND and
      LMND were more functionally impaired (P = 0.02). Separately, we identified 5
      patients with PUMND who developed LMND long after 48 months (range, 50-127
      months). CONCLUSIONS: PLS belongs to the ALS spectrum, and perhaps all cases
      eventually develop LMND.

PMID- 23169458
TI  - SOX2 expression is upregulated in adult spinal cord after contusion injury in
      both oligodendrocyte lineage and ependymal cells.
AB  - The upregulation of genes normally associated with development may occur in the
      adult after spinal cord injury (SCI). To test this, we performed real-time RT-PCR
      array analysis of mouse spinal cord mRNAs comparing embryonic day (E)14.5 spinal
      cord with intact adult and adult cord 1 week after a clinically relevant
      standardized contusion SCI. We found significantly increased expression of a
      large number of neural development- and stem cell-associated genes after SCI.
      These included Sox2 (sex determining region Y-box 2), a transcription factor that
      regulates self-renewal and potency of embryonic neural stem cells and is one of
      only a few key factors needed to induce pluripotency. In adult spinal cord of
      Sox2-EGFP mice, Sox2-EGFP was found mainly in the ependymal cells of the central
      canal. After SCI, both mRNA and protein levels of Sox2 were significantly
      increased at and near the injury site. By 1 day, Sox2 was upregulated in NG2(+)
      oligodendrocyte progenitor cells (OPC) in the spared white matter. By 3 days,
      Sox2-EGFP ependymal cells had increased proliferation and begun to form multiple
      layers and clusters of cells in the central lesion zone of the cord. Expression
      of Sox2 by NG2(+) cells had declined by 1 week, but increased numbers of other
      Sox2-expressing cells persisted for at least 4 weeks after SCI in both mouse and
      rat models. Thus, SCI upregulates many genes associated with development and
      neural stem cells, including the key transcription factor Sox2, which is
      expressed in a pool of cells that persists for weeks after SCI.

PMID- 23169459
TI  - Solid-state NMR studies of micelle-templated mesoporous solids.
AB  - In this tutorial review we intend to give an overview of the potential of NMR
      spectroscopy, and in particular solid-state NMR, in characterising micelle
      templated mesoporous materials. Different topics are covered including the study
      of formation mechanisms, the characterisation of structures, textures, surfaces
      and interfaces, functionalisation, dynamic properties and structure-reactivity
      correlations. Some selected examples illustrate the variety of information
      provided by this spectroscopy. Particular attention is paid to recent
      technological and/or methodological developments.

PMID- 23169460
TI  - CD44 enhances tumor formation and lung metastasis in experimental osteosarcoma
      and is an additional predictor for poor patient outcome.
AB  - Formation of metastases in the lungs is the major cause of death in patients
      suffering from osteosarcoma (OS). Metastases at presentation and poor response to
      preoperative chemotherapy are strong predictors for poor patient outcome. The
      elucidation of molecular markers that promote metastasis formation and/or
      chemoresistance is therefore of importance. CD44 is a plasma membrane
      glycoprotein that binds to the extracellular matrix component hyaluronan (HA) and
      has been shown to be involved in metastasis formation in a variety of other
      tumors. Here we investigated the role of CD44 expression on OS tumor formation
      and metastasis. High CD44 expression, evaluated with a tissue microarray
      including samples from 53 OS patients and stained with a pan-CD44 antibody
      (Hermes3), showed a tendency (p < 0.08) to shortened overall survival. However,
      nonresponders and patients with lung metastases and high CD44 expression had
      significantly poorer prognosis than patients with low CD44 expression.
      Overexpression of the standard CD44 isoform (CD44s) and its HA-binding defective
      mutant R41A in osteoblastic SaOS-2 cells resulted in HA-independent higher
      migration rates and increased chemoresistance, partially dependent on HA. In an
      orthotopic mouse model of OS, overexpression of CD44s in SaOS-2 cells resulted in
      an HA-dependent increased primary tumor formation and increased numbers of
      micrometastases and macrometastases in the lungs. In conclusion, although CD44
      failed to be an independent predictor for patient outcome in this limited cohort
      of OS patients, increased CD44 expression was associated with even worse survival
      in patients with chemoresistance and with lung metastases. CD44-associated
      chemoresistance was also observed in vitro, and increased formation of lung
      metastases was found in vivo in SCID mice.

PMID- 23169461
TI  - The discovery of new cyanobactins from Cyanothece PCC 7425 defines a new
      signature for processing of patellamides.
AB  - Cyanobactins, including patellamides, are a group of cyanobacterial post
      translationally modified ribosomal cyclic peptides. The final product should in
      theory be predictable from the sequence of the precursor peptide and the
      associated tailoring enzymes. Understanding the mechanism and recognition
      requirements of these enzymes will allow their rational engineering. We have
      identified three new cyanobactins from a Cyanothece PCC 7425 culture subjected to
      a heat shock. One of these compounds revealed a novel signature signal for ThcA,
      the subtilisin-like serine protease that is homologous to the patellamide
      protease PatA. The crystal structure of the latter and modelling studies allow
      rationalisation of the recognition determinants for both enzymes, consistent with
      the ribosomal biosynthetic origin of the new compounds.

PMID- 23169462
TI  - Normalizing the supernormal: the formation of the "Gesellschaft fur
      Psychologische Forschung" ("Society for Psychological Research"), C. 1886-1890.
AB  - This paper traces the formation of the German "Gesellschaft fur psychologische
      Forschung" ("Society for Psychological Research"), whose constitutive branches in
      Munich and Berlin were originally founded as inlets for alternatives to Wundtian
      experimental psychology from France and England, that is, experimental researches
      into hypnotism and alleged supernormal phenomena. By utilizing the career
      trajectories of Max Dessoir and Albert von Schrenck-Notzing as founding members
      of the "Gesellschaft," this paper aims to open up novel perspectives regarding
      extra-scientific factors involved in historically determining the epistemological
      and methodological boundaries of nascent psychology in Germany. 

PMID- 23169467
TI  - Cell signalling: hedgehog puts a damper on autophagy.

PMID- 23169466
TI  - TALENs: a widely applicable technology for targeted genome editing.
AB  - Engineered nucleases enable the targeted alteration of nearly any gene in a wide
      range of cell types and organisms. The newly-developed transcription activator
      like effector nucleases (TALENs) comprise a nonspecific DNA-cleaving nuclease
      fused to a DNA-binding domain that can be easily engineered so that TALENs can
      target essentially any sequence. The capability to quickly and efficiently alter
      genes using TALENs promises to have profound impacts on biological research and
      to yield potential therapeutic strategies for genetic diseases.

PMID- 23169468
TI  - An independent audit of the Australian food industry's voluntary front-of-pack
      nutrition labelling scheme for energy-dense nutrition-poor foods.
AB  - BACKGROUND/OBJECTIVE: Since 2006, the Australian food industry has promoted its
      front-of-pack (FOP) food labelling system-the Daily Intake Guide (DIG)-as a
      success story of industry self-regulation. With over 4000 products already
      voluntary featuring the DIG, the industry argues that government regulation of
      FOP nutrition labelling is simply unnecessary. However, no independent audit of
      the industry's self-regulation has ever been undertaken and we present the first
      such Australian data. SUBJECTS/METHODS: Energy-dense nutrient-poor (EDNP) snacks
      were audited at nine Australian supermarkets, including biscuits, candy, ice
      creams, chocolates, crisps, sports drinks, energy drinks, flavoured milks,
      sweetened juices and soft drinks. In these categories nutrition labels were
      recorded for 728 EDNP products in various packaging sizes. RESULTS: The DIG was
      displayed on 66% of audited EDNP products but most of these (75%) did not report
      saturated fat and sugar content. Only generic supermarket EDNP products were
      likely to display saturated fat and sugar content, compared with very few branded
      products (48% vs 4%, P<0.001). Branded products not displaying fat and sugar
      content contained on average 10-times more saturated fat than those displaying
      such (10% vs 1% DI, P<0.001) and nearly twice as much sugar (21 vs 13% DI,
      P<0.05). CONCLUSIONS: Most Australian manufacturers of EDNP products have adopted
      the DIG; consistent with industry claims of widespread adoption, but almost all
      still avoid displaying the high saturated fat and sugar content of their products
      by opting for the 'energy alone' option, violating the industry's own voluntarily
      guidelines and highlighting serious weaknesses with the industry's self
      regulation.

PMID- 23169469
TI  - Energy intake and sources of nutritional support in patients with head and neck
      cancer--a randomised longitudinal study.
AB  - BACKGROUND/OBJECTIVES: Malnutrition decreases the cancer patient's ability to
      manage treatment, affects quality of life and survival, and is common among head
      and neck (HN) cancer patients due to the tumour location and the treatment
      received. In this study, advanced HN cancer patients were included and followed
      during 2 years in order to measure their energy intake, choice of energy sources
      and to assess problems with dysphagia. The main purpose was to explore when and
      for how long the patients had dysphagia and lost weight due to insufficient
      intake and if having a PEG (percutaneous endoscopic gastrostomy) in place for
      enteral nutrition made a difference. SUBJECTS/METHODS: One hundred thirty-four
      patients were included and randomised to either a prophylactic PEG for early
      enteral feeding or nutritional care according to clinical praxis. At seven time
      points weight, dysphagia and energy intake (assessed as oral, nutritional
      supplements, enteral and parenteral) were measured. RESULTS: Both groups lost
      weight the first six months due to insufficient energy intake and used enteral
      nutrition as their main intake source; no significant differences between groups
      were found. Problems with dysphagia were vast during the 6 months. At the 6-, 12-
      and 24-month follow-ups both groups reached estimated energy requirements and
      weight loss ceased. Oral intake was the major energy source after 1 year.
      CONCLUSIONS: HN cancer patients need nutritional support and enteral feeding for
      a long time period during and after treatment due to insufficient energy intake.
      A prophylactic PEG did not significantly improve the enteral intake probably due
      to treatment side effects.

PMID- 23169470
TI  - Aged garlic extract reduces blood pressure in hypertensives: a dose-response
      trial.
AB  - BACKGROUND/OBJECTIVES: Hypertension affects about 30% of adults worldwide. Garlic
      has blood pressure-lowering properties and the mechanism of action is
      biologically plausible. Our trial assessed the effect, dose-response,
      tolerability and acceptability of different doses of aged garlic extract as an
      adjunct treatment to existing antihypertensive medication in patients with
      uncontrolled hypertension. SUBJECTS/METHODS: A total of 79 general practice
      patients with uncontrolled systolic hypertension participated in a double-blind
      randomised placebo-controlled dose-response trial of 12 weeks. Participants were
      allocated to one of three garlic groups with either of one, two or four capsules
      daily of aged garlic extract (240/480/960 mg containing 0.6/1.2/2.4 mg of S
      allylcysteine) or placebo. Blood pressure was assessed at 4, 8 and 12 weeks and
      compared with baseline using a mixed-model approach. Tolerability was monitored
      throughout the trial and acceptability was assessed at 12 weeks by questionnaire.
      RESULTS: Mean systolic blood pressure was significantly reduced by 11.8+/-5.4 mm
      Hg in the garlic-2-capsule group over 12 weeks compared with placebo (P=0.006),
      and reached borderline significant reduction in the garlic-4-capsule group at 8
      weeks (-7.4+/-4.1 mm Hg, P=0.07). Changes in systolic blood pressure in the
      garlic-1-capsule group and diastolic blood pressure were not significantly
      different to placebo. Tolerability, compliance and acceptability were high in all
      garlic groups (93%) and highest in the groups taking one or two capsules daily.
      CONCLUSIONS: Our trial suggests aged garlic extract to be an effective and
      tolerable treatment in uncontrolled hypertension, and may be considered as a safe
      adjunct treatment to conventional antihypertensive therapy.

PMID- 23169471
TI  - Overall and abdominal adiposity and hypertriglyceridemia among Korean adults: the
      Korea National Health and Nutrition Examination Survey 2007-2008.
AB  - BACKGROUND/OBJECTIVES: Obesity is associated with increased triglyceride levels.
      We examined whether overall obesity (body mass index (BMI)) and abdominal obesity
      (waist circumference (WC)) are independently associated with hypertriglyceridemia
      among the Korean population. SUBJECTS/METHODS: A national sample of 5036 Koreans
      aged 19-64 was examined with cross-sectional surveys, the Korea National Health
      and Nutrition Examination Survey, in 2007 and 2008. BMI, WC and other lifestyle
      information were assessed. RESULTS: We documented 1344 cases (26.7%) of
      hypertriglyceridemia (fasting triglycerides of >150 mg/dl). Both BMI and WC were
      each independently associated with hypertriglyceridemia. Multivariate odds ratios
      (ORs) of increasing categories of BMI (<18.5, 18.5<= - <23, 23<= - <25, 25<= -
      <28, >=28 kg/m2), were 0.49, 1.00 (reference), 1.26, 1.63 and 1.84, respectively
      (P=0.0007) adjusting for WC. There was a positive association between WC and
      hypertriglyceridemia across increasing quintiles of WC (multivariate-adjusted
      ORs: 1.00 (reference), 1.54, 2.54, 2.21 and 2.36; P<0.0001), adjusting for BMI.
      WC was positively related to hypertriglyceridemia in both gender. However, only
      women's BMI was independently associated with hypertriglyceridemia after
      adjusting for WC. The joint relation between BMI and WC and hypertriglyceridemia
      showed that within each BMI category, higher WC predicted a greater prevalence of
      hypertriglyceridemia and vice versa. The receiver operating characteristic curves
      indicated that BMI (0.69) and WC (0.72) were similar in predicting
      hypertriglyceridemia. CONCLUSIONS: Both BMI and WC were strongly independently
      associated with hypertriglyceridemia among the population. Both measurements
      should be considered for use in assessing health risk at clinical settings and
      epidemiologic research among Asian population.

PMID- 23169472
TI  - Zinc for treating of children and adolescents with attention-deficit
      hyperactivity disorder: a systematic review of randomized controlled clinical
      trials.
AB  - This study systematically reviews the randomized clinical trials examining the
      effect of zinc on attention-deficit hyperactivity disorder (ADHD), searching the
      PubMed/Medline and Scholar Google databases. All randomized controlled trials
      that examined zinc as the intervention, and ADHD as the primary outcome were
      included. Only three randomized controlled trials, one which included a community
      sample and two that included clinical samples, met inclusion criteria. The only
      trial that was well controlled and randomized according to the baseline zinc
      level showed that using zinc, either alone or in combination with stimulants, did
      not improve ADHD. Considering the lack of clear evidence for the effect of zinc
      on ADHD and the possible effect of zinc on the nervous system, more clinical
      studies are needed to prove or disprove the effect of zinc as a monotherapy or
      adjuvant therapy.

PMID- 23169473
TI  - Red and processed meat consumption and risk of stroke: a meta-analysis of
      prospective cohort studies.
AB  - BACKGROUND/OBJECTIVES: Epidemiological evidence is suggestive, but inconclusive,
      for an association between consumption of red and processed meat and risk of
      stroke. We aimed to assess this association by conducting a meta-analysis of
      prospective cohort studies. SUBJECTS/METHODS: We performed a literature search on
      PubMed database through June 2012 to identify prospective cohort studies of red
      and processed meat intake in relation to risk of stroke. Reference lists of the
      retrieved articles were also reviewed. Both fixed-effects and random-effects
      model were assumed to compute the summary risk estimates. RESULTS: Five large
      independent prospective cohort studies were identified. These studies contained a
      total of 2 39 251 subjects and 9593 stroke events. Comparing the highest category
      of consumption with lowest category, the pooled relative risks (RRs) of total
      stroke were 1.15 (95% confidence interval (CI), 1.05-1.25) for total meat (red
      and processed meat combined) (n=4), 1.09 (95% CI, 1.01-1.18) for red meat (n=5)
      and 1.14 (95% CI, 1.05-1.25) for processed meat (n=5); the corresponding RRs of
      ischemic stroke (highest vs lowest quintile) were 1.15 (95% CI, 1.04-1.28),
      1.13(95% CI, 1.01-1.25) and 1.19 (95% CI, 1.08-1.31). Consumption of red and/or
      processed meat was not associated with hemorrhagic stroke. In the dose-response
      analysis, the risk of stroke increased significantly by 10% and 13% for each 100
      g per day increment in total and red meat consumption, respectively, and by 11%
      for each 50 g per day increment in processed meat consumption. CONCLUSION:
      Findings from this meta-analysis indicate that consumption of red and/or
      processed meat increase risk of stroke, in particular, ischemic stroke.

PMID- 23169474
TI  - Improving outcomes in gastrointestinal cancer.

PMID- 23169475
TI  - Very low PSA concentrations and deletions of the KLK3 gene.
AB  - BACKGROUND: Prostate-specific antigen (PSA), a widely used biomarker for prostate
      cancer (PCa), is encoded by a kallikrein gene (KLK3, kallikrein-related peptidase
      3). Serum PSA concentrations vary in the population, with PCa patients generally
      showing higher PSA concentrations than control individuals, although a small
      proportion of individuals in the population display very low PSA concentrations.
      We hypothesized that very low PSA concentrations might reflect gene-inactivating
      mutations in KLK3 that lead to abnormally reduced gene expression. METHODS: We
      have sequenced all KLK3 exons and the promoter and searched for gross deletions
      or duplications in KLK3 in the 30 individuals with the lowest observed PSA
      concentrations in a sample of approximately 85 000 men from the Prostate Testing
      for Cancer and Treatment (ProtecT) study. The ProtecT study examines a community
      based population of men from across the UK with little prior PSA testing.
      RESULTS: We observed no stop codons or frameshift mutations, but we did find 30
      single-base genetic variants, including 3 variants not described previously.
      These variants included missense variants that could be functionally inactivating
      and splicing variants. At this stage, however, we cannot confidently conclude
      whether these variants markedly lower PSA concentration or activity. More
      importantly, we identified 3 individuals with different large heterozygous
      deletions that encompass all KLK3 exons. The absence of a functional copy of KLK3
      in these individuals is consistent with their reduced serum PSA concentrations.
      CONCLUSIONS: The clinical interpretation of the PSA test for individuals with
      KLK3 gene inactivation could lead to false-negative PSA findings used for
      screening, diagnosis, or monitoring of PCa.

PMID- 23169476
TI  - Six-minute walk test in healthy children: is the leg length important?
AB  - RATIONALE: Measures as height, age, and weight influence the six-minute walk test
      (6MWT). It was shown that children's true leg length (TLL) influence the 6MWT
      distance but so far it has never been evaluated how much this variable could
      predict the distance walked related to height. Our hypothesis is that there
      should not have any significant difference between models including height or
      TLL. OBJECTIVE: To establish and to compare the predicted walked distance of
      healthy children in the 6MWT by two distinct models, one including TLL and other
      including height. METHODS: Observational cross sectional study. A total of 161
      healthy children (84 girls, 52.2%), 6-13 years old from three local primary and
      secondary schools. Two 6MWT were performed following ATS guidelines. Weight,
      height, and TLL were measured. The longer walked distance was selected for
      statistical analysis. RESULTS: Anthropometric data were similar for both genders
      into each group of age. Mean (+/-SD) walked distances in whole group were: boys
      704.4 m (77.7); girls 681.6 m (67.9; P = 0.049). In the univariate regression to
      predict the distance walked, the adjusted coefficients to TLL and height were in
      boys: 0.46 and 0.39; and in girls: 0.35 and 0.29, respectively. After adjusting
      for age and weight, the residuals of the two equations were not significantly
      different (P = 0.998). CONCLUSION: The model including TLL to predict the walked
      distance by healthy children explained more of the variation on the walked
      distance in the 6MWT than the model using the height but without significant
      difference between the models.

PMID- 23169477
TI  - Suppressing the growth of rectal cancer xenografts derived from patient tumors by
      an adenovector expressing small hairpin RNA targeting Bcl-XL.
AB  - BACKGROUND: Bcl-XL, a mitochondria membrane protein, is overexpressed in
      colorectal cancers and promotes cell survival. We have previously shown that the
      adenovector expressing small hairpin (sh)RNA targeting Bcl-XL could induce
      significantly apoptosis in colon cancer cells. In the present study, we aimed to
      further detect the anti-cancer effect of adenovector expressing the shRNA
      targeting Bcl-XL (Ad/Bcl-XL shRNA) on rectal cancer xenografts that were derived
      from patient tumors. METHODS: We first established three rectal cancer
      xenografts. These xenografts were subsequently treated with Ad/Bcl-XL shRNA alone
      or in combination with 5-fluouracil (5-Fu). Finally, the inhibition of tumor
      growth, survival time and induction of apoptosis were analyzed. RESULTS: The
      results obtained demonstrated that Ad/Bcl-XL shRNA could effectively suppress the
      tumor growth of all three rectal cancer xenografts and prolong their survival
      time. After being combined with 5-Fu, the suppressing effect of Ad/Bcl-XL shRNA
      was enhanced further. In addition, the data also showed that Ad/Bcl-XL shRNA
      combined with 5-Fu could significantly increase the apoptotic ratio in the rectal
      cancer xenograft. CONCLUSIONS: These data indicate that Ad/Bcl-XL shRNA with or
      without 5-Fu has effective anti-tumor effects on the patient tumor-derived rectal
      cancer xenografts, suggesting that it could be a potential strategy for rectal
      cancer therapy.

PMID- 23169478
TI  - Halogen bonding from a hard and soft acids and bases perspective: investigation
      by using density functional theory reactivity indices.
AB  - Halogen bonds between the trifluoromethyl halides CF(3)Cl, CF(3)Br and CF(3)I,
      and dimethyl ether, dimethyl sulfide, trimethylamine and trimethyl phosphine were
      investigated using Pearson's hard and soft acids and bases (HSAB) concept with
      conceptual DFT reactivity indices, the Ziegler-Rauk-type energy-decomposition
      analysis, the natural orbital for chemical valence (NOCV) framework and the non
      covalent interaction (NCI) index. It is found that the relative importance of
      electrostatic and orbital (charge transfer) interactions varies as a function of
      both the donor and acceptor molecules. Hard and soft interactions were
      distinguished and characterised by atomic charges, electrophilicity and local
      softness indices. Dual-descriptor plots indicate an orbital sigma hole on the
      halogen similar to the electrostatic sigma hole manifested in the molecular
      electrostatic potential. The predicted high halogen-bond-acceptor affinity of N
      heterocyclic carbenes was evidenced in the highest complexation energy for the
      hitherto unknown CF(3) I.NHC complex. The dominant NOCV orbital represents an
      electron-density deformation according to a n->sigma*-type interaction. The
      characteristic signal found in the reduced density gradient versus electron
      density diagram corresponds to the non-covalent interaction between contact atoms
      in the NCI plots, which is the manifestation of halogen bonding within the NCI
      theory. The unexpected C-X bond strengthening observed in several cases was
      rationalised within the molecular orbital framework.

PMID- 23169479
TI  - microRNA expression profile in a large series of bladder tumors: identification
      of a 3-miRNA signature associated with aggressiveness of muscle-invasive bladder
      cancer.
AB  - The aim of this study was to evaluate the expression levels of microRNAs (miRNAs)
      in bladder tumors in order to identify miRNAs involved in bladder carcinogenesis
      with potential prognostic implications. Expression levels of miRNAs were assessed
      by quantitative real-time RT-PCR in 11 human normal bladder and 166 bladder tumor
      samples (86 non-muscle-invasive bladder cancer (NMIBC) and 80 muscle-invasive
      bladder cancer (MIBC)). The expression level of 804 miRNAs was initially measured
      in a well-defined series of seven NMIBC, MIBC and normal bladder samples
      (screening set). The most strongly deregulated miRNAs in tumor samples compared
      to normal bladder tissue were then selected for RT-PCR validation in a well
      characterized independent series of 152 bladder tumors (validation set), and in
      six bladder cancer cell lines. Expression levels of these miRNAs were tested for
      their association with clinical outcome. A robust group of 15 miRNAs was found to
      be significantly deregulated in bladder cancer. Except for two miRNAs, miR-146b
      and miR-9, which were specifically upregulated in MIBC, the majority of miRNAs (n
      = 13) were deregulated in the same way in the two types of bladder tumors,
      irrespective of pathological stage : three miRNAs were upregulated (miR-200b, miR
      182 and miR-138) and the other 10 miRNAs were downregulated (miR-1, miR-133a, miR
      133b, miR-145, miR-143, miR-204, miR-921, miR-1281, miR-199a and miR-199b). A 3
      miRNA signature (miR-9, miR-182 and miR-200b) was found to be related to MIBC
      tumor aggressiveness and was associated with both recurrence-free and overall
      survival in univariate analysis with a trend to significance in the multivariate
      analysis (p = 0.05). Our results suggested a promising individual prognostic
      value of these new markers.

PMID- 23169480
TI  - Reliability and validity of the Italian self-evaluation of communication
      experiences after laryngeal cancer questionnaire.
AB  - BACKGROUND: The Self-Evaluation of Communication Experiences after Laryngeal
      Cancer (SECEL) questionnaire assesses the impact of total laryngectomy on
      communication-related quality of life (QOL). This study evaluates the Italian
      version of the SECEL (I-SECEL), including reliability, concurrent validity, and
      differences in scores between patients who undergo either total laryngectomy or
      partial laryngectomy. METHODS: Eighty patients who underwent either total
      laryngectomy or partial laryngectomy completed the I-SECEL twice and the Voice
      Handicap Index (VHI) and Short Form Health Survey (SF-36) questionnaires once.
      Voice recordings were used for objective and perceptual assessment. RESULTS: The
      I-SECEL demonstrated good test-retest reliability and internal consistency for 2
      of 3 subscales. Correlations were moderate to strong between most of the I-SECEL
      scales and the VHI/SF-36 scales. The I-SECEL scales demonstrated moderate
      associations with most perceptual and objective measures. CONCLUSION: Preliminary
      evidence supports the convergent validity, test-retest reliability, and internal
      consistency of the I-SECEL, notwithstanding low internal consistency and test
      retest reliability for 1 subscale.

PMID- 23169481
TI  - Polysialic acid expression is not necessary for motor neuron target selectivity.
AB  - INTRODUCTION: Recovery after peripheral nerve lesions depends on guiding axons
      back to their targets. Polysialic acid upregulation by regrowing axons has been
      proposed recently as necessary for this target selectivity. METHODS: We
      reexamined this proposition using a cross-reinnervation model whereby axons from
      obturator motor neurons that do not upregulate polysialic acid regenerated into
      the distal femoral nerve. Our aim was to assess their target selectivity between
      pathways to muscle and skin. RESULTS: After simple cross-repair, obturator motor
      neurons showed no pathway preference, but the same repair with a shortened skin
      pathway resulted in selective targeting of these motor neurons to muscle by a
      polysialic acid-independent mechanism. CONCLUSION: The intrinsic molecular
      differences between motor neuron pools can be overcome by manipulation of their
      access to different peripheral nerve pathways such that obturator motor neurons
      preferentially project to a terminal nerve branch to muscle despite not
      upregulating the expression of polysialic acid.

PMID- 23169483
TI  - Camptocormia as a late presentation in a manifesting carrier of duchenne muscular
      dystrophy.
AB  - INTRODUCTION: Camptocormia, or bent spine syndrome, is an abnormal posture
      consisting of forward flexion of the spine that disappears when a patient is
      supine. It is associated with a wide variety of myopathic disorders that affect
      paraspinal muscles, including inflammatory and inherited myopathies. METHODS: We
      describe a woman who presented with camptocormia in her eighth decade. RESULTS:
      Skeletal muscle biopsy showed mild nonspecific changes, but her family history
      was significant for a son who died of Duchenne muscular dystrophy (DMD). Genetic
      analysis of DMD confirmed that she was a heterozygous carrier of a mutation.
      CONCLUSIONS: In the absence of any alternate explanation, we interpret her
      symptoms to be a manifestation of her DMD carrier state. To our knowledge, this
      represents the first reported example of camptocormia as the presenting symptom
      in a carrier and suggests that a manifesting carrier state should be considered
      in the differential diagnosis for women with unexplained camptocormia.

PMID- 23169482
TI  - Probing tissue microstructure with restriction spectrum imaging: Histological and
      theoretical validation.
AB  - Water diffusion magnetic resonance imaging (dMRI) is a powerful tool for studying
      biological tissue microarchitectures in vivo. Recently, there has been increased
      effort to develop quantitative dMRI methods to probe both length scale and
      orientation information in diffusion media. Diffusion spectrum imaging (DSI) is
      one such approach that aims to resolve such information based on the three
      dimensional diffusion propagator at each voxel. However, in practice, only the
      orientation component of the propagator function is preserved when deriving the
      orientation distribution function. Here, we demonstrate how a straightforward
      extension of the linear spherical deconvolution (SD) model can be used to probe
      tissue orientation structures over a range (or "spectrum") of length scales with
      minimal assumptions on the underlying microarchitecture. Using high b-value
      Cartesian q-space data on a rat brain tissue sample, we demonstrate how this
      "restriction spectrum imaging" (RSI) model allows for separating the volume
      fraction and orientation distribution of hindered and restricted diffusion, which
      we argue stems primarily from diffusion in the extraneurite and intraneurite
      water compartment, respectively. Moreover, we demonstrate how empirical RSI
      estimates of the neurite orientation distribution and volume fraction capture
      important additional structure not afforded by traditional DSI or fixed-scale SD
      like reconstructions, particularly in gray matter. We conclude that incorporating
      length scale information in geometric models of diffusion offers promise for
      advancing state-of-the-art dMRI methods beyond white matter into gray matter
      structures while allowing more detailed quantitative characterization of water
      compartmentalization and histoarchitecture of healthy and diseased tissue.

PMID- 23169484
TI  - "I'm talking about pain": sickle cell disease patients with extremely high
      hospital use.
AB  - BACKGROUND: A small minority of sickle cell disease patients accounts for the
      majority of inpatient hospital days. Admitted as often as several times a month,
      over successive years, this cohort of patients has not been studied in depth
      despite their disproportionate contribution to inpatient hospital costs in sickle
      cell disease. OBJECTIVE: To characterize the subjective experience of extremely
      high hospital use in patients with sickle cell disease, and generate hypotheses
      about the antecedents and consequences of this phenomenon. DESIGN: Qualitative
      study involving in-depth, open-ended interviews using a standardized interview
      guide. SETTING: A single urban academic medical center. PARTICIPANTS: Eight
      individuals, of varying age and gender, identified as the sickle cell disease
      patients who are among the highest hospital use patients over a 3-year period.
      RESULTS: A common narrative emerged from the interview transcripts. Participants
      were exposed to the hospital environment and intravenous (IV) opioids at a young
      age, and this exposure was associated with extremely high hospital use in
      adulthood, evident in descriptions of multiple dimensions of their lives: pain
      and opioid medication use, interpersonal relationships, and personal development.
      CONCLUSIONS: Our results suggest a systematic, self-reinforcing process of
      isolation from mainstream society, support structures, and caregivers, based on
      increasing hospitalization, growing dependency on opioid medications, as well as
      missed developmental milestones. Further study and interventions should be geared
      towards breaking this spiraling cycle with long-term strategies in disease
      management and social integration.

PMID- 23169485
TI  - Immunoparesis and monoclonal gammopathy of undetermined significance are
      disassociated in advanced age.
AB  - Immunoparesis and a skewed serum free light chain (FLC) ratio are indicators of
      immune dysfunction predictive of progression from monoclonal gammopathy of
      undetermined significance (MGUS) to multiple myeloma (MM). Previous studies have
      reported increased prevalence of MGUS by age, but no study has examined the
      relationship between immunoparesis and abnormal FLC ratios in the elderly. We
      screened 453 older adults (median age, 80 years; range, 65-96) to characterize
      the patterns of immunoparesis and abnormal FLC ratio in relation to MGUS. We
      defined MGUS in 4.4% of the subjects; the prevalence was 12.5% among individuals
      of >90 years. In MGUS (vs. non-MGUS) cases, immunoparesis and abnormal FLC ratios
      were detected in 70.0% (vs. 49.0%; P = 0.07) and 50.0% (vs. 12.9%; P = 0.0001),
      respectively. Based on small numbers, MGUS patients with abnormal FLC ratio were
      borderline (P = 0.07) more likely to have immunoparesis. Overall, the prevalence
      of immunoparesis varied in a nonlinear fashion, with lowest frequencies in the
      youngest and oldest groups. Our observed disassociation between MGUS prevalence
      and impaired immunoglobulin production suggests that separate mechanisms are
      involved in the development of MGUS and immunoparesis in advanced age. These
      findings emphasize the need for molecularly defined methods to characterize
      myeloma precursor states and better predict progression to MM.

PMID- 23169486
TI  - Tetranuclear homo- (Zn(II)4 and Cd(II)4) and hetero-metal (Zn(II)2Tb(III)2 and
      Cd(II)2Tb(III)2) complexes with a pair of carboxylate ligands in a rare
      eta2:eta2:MU4-bridging mode: syntheses, structures and emission properties.
AB  - Four tetranuclear complexes involving both homo- and hetero-metal combinations,
      viz. [Zn(II)(2)L(2)(MU(4)-PhCOO)(2)Zn(II)(2)(hfac)(2)] (1), [Cd(II)(2)L(2)(MU(4)
      PhCOO)(2)Cd(II)(2)(hfac)(2)] (2), [Zn(II)(2)L(2)(MU(4)
      PhCOO)(2)Tb(III)(2)(hfac)(4)] (3), and [Cd(II)(2)L(2)(MU(4)
      PhCOO)(2)Tb(III)(2)(hfac)(4)] (4) have been prepared following a single-pot
      synthesis protocol using N,N'-dimethyl-N,N'-bis(2-hydroxy-3,5
      dimethylbenzyl)ethylenediamine (H(2)L) as a primary ligand. Both benzoate and
      hexafluoroacetylacetonate (hfac(-)), used here as ancillary ligands, play crucial
      roles in generating a tetranuclear core with high thermodynamic stability. Oxygen
      atoms of each carboxylate moiety bind all the four metal centers together in a
      rare eta(2):eta(2):MU(4)-bridging mode as confirmed by X-ray crystallography. In
      the homo-metallic complexes (1 and 2), the metal centers are all lying in a
      square plane, each occupying a corner, and remain connected together by oxygen
      bridges forming octagonal metallacrowns. These structures remain intact in
      solution as confirmed by (1)H NMR spectroscopy and photoluminescent studies. In
      the hetero-metal complexes (3 and 4), the metal centers are arrayed in alternate
      positions of the tetranuclear core. The Tb(III) centers have eight coordinate bi
      capped trigonal prismatic coordination environments with different degrees of
      distortions. The all oxygen O(8) core surrounding each Tb(III) center is devoid
      of solvent molecules that make fluorescent emission from these molecules (3 and
      4) quite interesting. The hfac(-)-based (1)(pi-pi*) emissions observed in 1 and 2
      are quenched in 3 and 4. These sensitized Tb(III) emissions [(5)D(4)->(7)F(j); j
      = 6, 5, 4, and 3] are influenced by the local environments surrounding the 4f
      metal center. The lifetime for the luminescence decay of 3 ((5)D(4)->(7)F(5)
      transition) is about 1.5 times longer than that of 4 in all the solvents studied
      at 298 K.

PMID- 23169487
TI  - Olanzapine and food craving: a case control study.
AB  - BACKGROUND: Antipsychotic-induced weight gain is a problematic side effect. The
      mechanism is still not fully understood. Carbohydrate (and possibly other food)
      cravings have been suggested in literature, but not been systematically
      investigated. OBJECTIVES: To investigate the hypothesis that food cravings,
      especially for carbohydrate, are responsible for olanzapine-induced weight gain.
      METHOD: A case control design was used to measure general and specific food
      cravings using Food Craving Inventory (White et al., 2002) in three groups:
      patients with a diagnosis of schizophrenia taking olanzapine (Number = 20) or
      typical antipsychotics (Number = 20) and in a healthy control group (Number =
      20). RESULTS: No statistically significant differences were found between the
      three groups in the craving scores. There was a trend in the typical group to
      show more cravings than other groups. CONCLUSION: Our study failed to prove the
      hypothesis that carbohydrate craving is responsible for olanzapine-induced weight
      gain. This conclusion is limited by the small number of the subjects included.

PMID- 23169488
TI  - Microfiltration applied to dairy streams: removal of bacteria.
AB  - Microfiltration applied in the dairy industry for bacteria removal is an
      important technology for extending the shelf life of milk while maintaining or
      even improving its organoleptic and nutritional properties. This article reviews
      the evolution of this technique over recent years and the advances currently
      being made in the field. The cited literature indicates the strategies used to
      overcome the main drawbacks of this type of operation, the most common operating
      conditions employed and the reduction degree of bacteria obtained.

PMID- 23169489
TI  - Plasma choline metabolites associate with metabolic stress among young overweight
      men in a genotype-specific manner.
AB  - OBJECTIVES: We aimed to test the hypotheses that (i) plasma choline metabolites
      differ between normal (body mass index (BMI)<25 kg m(-2)) and overweight (BMI ?25
      kg m(-2)) men, and (ii) an elevated BMI alters associations between plasma
      choline metabolites and indicators of metabolic stress. DESIGN: This was a cross
      sectional study. A one-time fasting blood sample was obtained for measurements of
      the choline metabolites and metabolic stress indicators (that is, serum alanine
      aminotransferase (ALT), glucose, high-density lipoprotein cholesterol, low
      density lipoprotein cholesterol, triglycerides and homocysteine), and for
      genotype determination. SUBJECTS: The analysis was conducted with 237 Mexican
      American men with a median age of 22 years. RESULTS: Compared with men with a
      normal BMI (n=98), those with an elevated BMI (n=139) had 6% lower (P=0.049)
      plasma betaine and an 11% lower (P=0.002) plasma betaine to choline ratio. Among
      men with an elevated BMI, plasma betaine and the plasma betaine to choline ratio
      positively associated (P?0.044) with a favorable serum cholesterol profile, and
      inversely associated (P=0.001) with serum ALT, a marker of liver dysfunction. The
      phosphatidylethanolamine N-methyltransferase (PEMT) 5465G?A (rs7946) genotype
      interacted (P?0.007) with the plasma betaine to choline ratio to modulate
      indicators of metabolic stress with stronger inverse associations observed among
      overweight men with the PEMT 5465GG genotype. CONCLUSIONS: Plasma choline
      metabolites predict metabolic stress among overweight men often in a genotype
      specific manner. The diminished betaine among overweight men coupled with the
      inverse association between betaine and metabolic stress suggest that betaine
      supplementation may be effective in mitigating some of the metabolic insults
      arising from lipid overload.

PMID- 23169490
TI  - Genomic analysis of Meckel-Gruber syndrome in Arabs reveals marked genetic
      heterogeneity and novel candidate genes.
AB  - Meckel-Gruber syndrome (MKS, OMIM #249000) is a multiple congenital malformation
      syndrome that represents the severe end of the ciliopathy phenotypic spectrum.
      Despite the relatively common occurrence of this syndrome among Arabs, little is
      known about its genetic architecture in this population. This is a series of 18
      Arab families with MKS, who were evaluated clinically and studied using
      autozygome-guided mutation analysis and exome sequencing. We show that autozygome
      guided candidate gene analysis identified the underlying mutation in the majority
      (n=12, 71%). Exome sequencing revealed a likely pathogenic mutation in three
      novel candidate MKS disease genes. These include C5orf42, Ellis-van-Creveld
      disease gene EVC2 and SEC8 (also known as EXOC4), which encodes an exocyst
      protein with an established role in ciliogenesis. This is the largest and most
      comprehensive genomic study on MKS in Arabs and the results, in addition to
      revealing genetic and allelic heterogeneity, suggest that previously reported
      disease genes and the novel candidates uncovered by this study account for the
      overwhelming majority of MKS patients in our population.

PMID- 23169491
TI  - Wilms' tumor in patients with 9q22.3 microdeletion syndrome suggests a role for
      PTCH1 in nephroblastomas.
AB  - Nephroblastoma (Wilms' tumor; WT) is the most common renal tumor of childhood. To
      date, several genetic abnormalities predisposing to WT have been identified in
      rare overgrowth syndromes. Among them, abnormal methylation of the 11p15 region,
      GPC3 and DIS3L2 mutations, which are responsible for Beckwith-Wiedemann, Simpson
      Golabi-Behmel and Perlman syndromes, respectively. However, the underlying cause
      of WT remains unknown in the majority of cases. We report three unrelated
      patients who presented with WT in addition to a constitutional 9q22.3
      microdeletion and dysmorphic/overgrowth syndrome. The size of the deletions was
      variable (ie, from 1.7 to 8.9 Mb) but invariably encompassed the PTCH1 gene.
      Subsequently, we identified a somatic PTCH1 nonsense mutation in the renal tumor
      of one patient. In addition, by array comparative genomic hybridization method,
      we analyzed the DNA extracted from the blood samples of nine patients with
      overgrowth syndrome and WT, but did not identify any deleterious chromosomal
      imbalances in these patients. These findings strongly suggest that patients with
      constitutional 9q22.3 microdeletion have an increased risk of WT, and that PTCH1
      have a role in the pathogenesis of nephroblastomas.

PMID- 23169492
TI  - The perspective from EASAC and FEAM on direct-to-consumer genetic testing for
      health-related purposes.
AB  - Direct-to-consumer (DTC) genetic testing services raise scientific, regulatory
      and ethical questions. A report was prepared by consultation with an expert
      Working Group and published by the academies of science (European Academies of
      Science Advisory Council, EASAC) and medicine (Federation of European Academies
      of Medicine, FEAM). This report reviews current scientific evidence, ascertains
      the principles that should underpin the options for action by policy-makers, and
      discusses the potential for devising proportionate and flexible regulation that
      enables future innovation, taking account of the work of other expert groups,
      most notably the European Society of Human Genetics. EASAC-FEAM concluded that
      DTC genetic testing has little clinical value at present, and expresses especial
      caution in several specific respects, for example relating to testing for high
      penetrance, serious disorders, prenatal screening, nutrigenomic and
      pharmacogenetic testing. It was emphasised that regulation must be on the basis
      that claims about the link between genetic marker and disease are scientifically
      valid. Other key issues to address include quality assurance (that includes the
      professional interpretation of results), transparent supply of accurate
      information, consideration of the implications for established health services,
      and clarification of consent procedures for any use of data for research
      purposes. There are important implications: for the European Commission, in
      revising the Directive on In Vitro Diagnostic Medical Devices; for professional
      bodies, in supporting training and guideline development; for the broader
      research community, in generating the evidence base; and for the public health
      community, in improving the routine translation of research advances into
      clinical practice.

PMID- 23169493
TI  - A focus group study on breast cancer risk presentation: one format does not fit
      all.
AB  - Identifying a strategy that would optimize both the communication and
      understanding of the individual breast cancer risk remains a considerable
      challenge. This study explored the preferences of women with a family history of
      breast cancer about six presentation formats of individual breast cancer risk, as
      calculated from a risk prediction model. Thirty-four unaffected women attending
      genetic counseling because of a family history of breast cancer participated in
      six focus groups conducted in Quebec City (2), Montreal (2) and Toronto (2),
      Canada. Six risk formats were presented for a fictitious case involving a 35-year
      old woman (1-numerical: cumulative risk probabilities by age until 80 years; 2
      risk curves: probabilities expressed in a risk curve that also provided a risk
      curve for a woman with no family history in first-degree relatives; 3-relative
      risk of breast cancer by age 80 years; 4 and 5-absolute risk of breast cancer and
      absolute chance of not developing breast cancer in the next 20 years; 6
      qualitative: color-coded figure). Participants were asked to indicate their
      appreciation of each format. A group discussion followed during which
      participants commented on each format. The most and least appreciated formats
      were risk curves and relative risk, respectively. Overall, participants advocated
      the use of formats that combine quantitative, qualitative and visual features.
      Using a combination of approaches to communicate individual breast cancer risks
      could be associated with higher satisfaction of counselees. Given the increasing
      use of risk prediction models, it may be relevant to consider the preferences of
      both the counselee and the professional.

PMID- 23169494
TI  - A tiered-layered-staged model for informed consent in personal genome testing.
AB  - In recent years, developments in genomics technologies have led to the rise of
      commercial personal genome testing (PGT): broad genome-wide testing for multiple
      diseases simultaneously. While some commercial providers require physicians to
      order a personal genome test, others can be accessed directly. All providers
      advertise directly to consumers and offer genetic risk information about dozens
      of diseases in one single purchase. The quantity and the complexity of risk
      information pose challenges to adequate pre-test and post-test information
      provision and informed consent. There are currently no guidelines for what should
      constitute informed consent in PGT or how adequate informed consent can be
      achieved. In this paper, we propose a tiered-layered-staged model for informed
      consent. First, the proposed model is tiered as it offers choices between
      categories of diseases that are associated with distinct ethical, personal or
      societal issues. Second, the model distinguishes layers of information with a
      first layer offering minimal, indispensable information that is material to all
      consumers, and additional layers offering more detailed information made
      available upon request. Finally, the model stages informed consent as a process
      by feeding information to consumers in each subsequent stage of the process of
      undergoing a test, and by accommodating renewed consent for test result updates,
      resulting from the ongoing development of the science underlying PGT. A tiered
      layered-staged model for informed consent with a focus on the consumer
      perspective can help overcome the ethical problems of information provision and
      informed consent in direct-to-consumer PGT.

PMID- 23169496
TI  - Halogen-bonding interactions with pi systems: CCSD(T), MP2, and DFT calculations.
AB  - Halogen bonding is a noncovalent interaction between a halogen atom and a
      nucleophilic site. Interactions involving the pi electrons of aromatic rings have
      received, up to now, little attention, despite the large number of systems in
      which they are present. We report binding energies of the interaction between
      either NCX or PhX (X = F, Cl, Br, I) and the aromatic benzene system as
      determined with the coupled cluster with perturbative triple excitations method
      [CCSD(T)] extrapolated at the complete basis set limit. Results are compared with
      those obtained by Moller-Plesset perturbation theory to second order (MP2) and
      density functional theory (DFT) calculations by using some of the most common
      functionals. Results show the important role of DFT in studying this interaction.

PMID- 23169495
TI  - Analysis of the effects of rare variants on splicing identifies alterations in
      GABAA receptor genes in autism spectrum disorder individuals.
AB  - A large-scale sequencing screen of X-linked synaptic genes in individuals with
      autism spectrum disorder (ASD) or schizophrenia (SCZ), two common
      neurodevelopmental disorders, identified many variants most of which have no
      easily predictable effect on gene function. In this report, we evaluated the
      impact of these rare missense and silent variants on gene splicing. For this
      purpose, we used complementary in silico analyses, in vitro minigene-based assays
      and RNA prepared from lymphoblastoid cells derived from patients with these
      mutations. Our goal was to identify the variants which might either create or
      disrupt an acceptor splice site, a donor splice site or an exonic splicing
      enhancer, thus leading to aberrant splicing that could be involved in the
      pathogenesis of ASD or SCZ. We identified truncating mutations in distinct X
      linked gamma-aminobutyric acid A (GABAA) receptor subunit-encoding genes, GABRQ
      and GABRA3, in two different families. Furthermore, missense and silent variants
      in nuclear RNA export factor 5 and histone deacetylase 6 were shown to partially
      disrupt the protein. While genes from the GABAergic pathway have previously been
      thought to be involved in the pathophysiology of ASD, this is the first report of
      ASD patients with truncating mutations in GABA receptors genes.

PMID- 23169497
TI  - Significant risk of falls in older cancer patients.

PMID- 23169498
TI  - Capturing data on colostomy formation in anal cancer.

PMID- 23169499
TI  - Improvement in progression-free survival in OCEANS bevacizumab arm: a critical
      point of view.

PMID- 23169500
TI  - Severe acute interstitial lung disease after crizotinib therapy in a patient with
      EML4-ALK-positive non-small-cell lung cancer.

PMID- 23169501
TI  - Adoptive transfer of epstein-barr virus (EBV) nuclear antigen 1-specific t cells
      as treatment for EBV reactivation and lymphoproliferative disorders after
      allogeneic stem-cell transplantation.
AB  - PURPOSE: Reactivation of Epstein-Barr virus (EBV) after allogeneic stem-cell
      transplantation (SCT) can lead to severe life-threatening infections and trigger
      post-transplantation lymphoproliferative disease (PTLD). Since EBV-specific T
      cells could prevent PTLD, cellular immunotherapy has been a promising treatment
      option. However, generation of antigen-specific T-cell populations has been
      difficult within a short time frame. PATIENTS AND METHODS: To improve
      availability in urgent clinical conditions, we developed a rapid protocol for
      isolation of polyclonal EBV nuclear antigen 1 (EBNA-1) -specific T cells by using
      an interferon gamma (IFN-gamma) capture technique. RESULTS: We report on the use
      of adoptive transfer of EBNA-1-specific T cells in 10 pediatric and adult
      patients with EBV viremia and/or PTLD after SCT. No acute toxicity or graft
      versus-host disease (GVHD) of more than grade 2 occurred as a result of adoptive
      T-cell transfer. In vivo expansion of transferred EBNA-1-specific T cells was
      observed in eight of 10 patients after a median of 16 days following adoptive
      transfer that was associated with clinical and virologic response in seven of
      them (70%). None of the responders had EBV-associated mortality. Within clinical
      responders, three patients were disease free by the day of last follow-up (2 to
      36 months), three patients died of other infectious complications, and one
      patient died as a result of relapse of malignancy. EBV-related mortality was
      observed in two of 10 patients, and another patient had ongoing viremia without
      clinical symptoms at last follow-up. CONCLUSION: Adoptive ex vivo transfer of
      EBNA-1-specific T cells is a feasible and well-tolerated therapeutic option,
      representing a fast and efficient procedure to achieve reconstitution of
      antiviral T-cell immunity after SCT.

PMID- 23169502
TI  - Postoperative adjuvant chemotherapy use in patients with stage II/III rectal
      cancer treated with neoadjuvant therapy: a national comprehensive cancer network
      analysis.
AB  - PURPOSE: Practice guidelines recommend that patients who receive neoadjuvant
      chemotherapy and radiation for locally advanced rectal cancer complete
      postoperative adjuvant systemic chemotherapy, irrespective of tumor downstaging.
      PATIENTS AND METHODS: The National Comprehensive Cancer Network (NCCN) Colorectal
      Cancer Database tracks longitudinal care for patients treated at eight specialty
      cancer centers across the United States and was used to evaluate how frequently
      patients with rectal cancer who were treated with neoadjuvant chemotherapy also
      received postoperative systemic chemotherapy. Patient and tumor characteristics
      were examined in a multivariable logistic regression model. RESULTS: Between
      September 2005 and December 2010, 2,073 patients with stage II/III rectal cancer
      were enrolled in the database. Of these, 1,193 patients receiving neoadjuvant
      chemoradiotherapy were in the analysis, including 203 patients not receiving any
      adjuvant chemotherapy. For those seen by a medical oncologist, the most frequent
      reason chemotherapy was not recommended was comorbid illness (25 of 50, 50%); the
      most frequent reason chemotherapy was not received even though it was recommended
      or discussed was patient refusal (54 of 74, 73%). After controlling for NCCN
      Cancer Center and clinical TNM stage in a multivariable logistic model, factors
      significantly associated with not receiving adjuvant chemotherapy were age,
      Eastern Cooperative Oncology Group performance status >= 1, on Medicaid or
      indigent compared with private insurance, complete pathologic response, presence
      of re-operation/wound infection, and no closure of ileostomy/colostomy.
      CONCLUSION: Even at specialty cancer centers, a sizeable minority of patients
      with rectal cancer treated with curative-intent neoadjuvant chemoradiotherapy do
      not complete postoperative chemotherapy. Strategies to facilitate the ability to
      complete this third and final component of curative intent treatment are
      necessary.

PMID- 23169503
TI  - Pegylated liposomal doxorubicin, rituximab, cyclophosphamide, vincristine, and
      prednisone in AIDS-related lymphoma: AIDS Malignancy Consortium Study 047.
AB  - PURPOSE: Infusional chemotherapy is efficacious in patients with AIDS-related
      lymphoma, but it may be difficult to administer. We studied standard agents with
      rituximab plus pegylated liposomal doxorubicin (DR-COP) in an attempt to provide
      a more practical approach to therapy while ascertaining rates of response,
      potential infectious complications, and prognostic role of biologic markers.
      PATIENTS AND METHODS: We conducted a prospective, multi-institutional phase II
      trial, employing (day 1) pegylated liposomal doxorubicin 40 mg/m(2), rituximab
      375 mg/m(2), cyclophosphamide 750 mg/m(2), vincristine 1.4 mg/m(2) (not > 2 mg),
      and prednisone 100 mg orally on days 1 through 5, with concomitant antiretroviral
      therapy. RESULTS: In 40 evaluable patients, median CD4 cells was 114/MUL (range,
      5 to 1,026/MUL), and median HIV-1 viral load (VL) was 25,000 copies/mL. High or
      intermediate/high age-adjusted International Prognostic Index was present in 28%.
      Overall response was 67.5%, with complete remission in 47.5% (95% CI, 31.5 to
      63.9). Of 19 complete responders, 84% had extranodal disease, 47% had CD4 <
      100/MUL, and 47% had VL > 50,000 copies/mL; one relapsed. With 25.5-month median
      follow-up, 62% (95% CI, 44 to 75) of patients remain alive. Sixteen patients
      (40%) experienced 22 infections, with grade 4 in only two (5%). No patient died
      as a result of infection during treatment; one had opportunistic infection.
      CONCLUSION: Profound immunodeficiency and high HIV-1 viral load do not preclude
      attainment of complete response after DR-COP with highly active antiretroviral
      therapy. The regimen is tolerable, and use of rituximab was not associated with
      death as a result of infection during treatment. This approach may be useful in
      patients in whom the more intensive infusional regimens are impractical.

PMID- 23169504
TI  - Bevacizumab-associated osteonecrosis of the wrist and knee in three pediatric
      patients with recurrent CNS tumors.

PMID- 23169505
TI  - Improving T-cell therapy for epstein-barr virus lymphoproliferative disorders.

PMID- 23169506
TI  - Primary hepatic lymphoma presenting as an isolated solitary hepatic cyst.

PMID- 23169507
TI  - Active tuberculosis during temsirolimus and bevacizumab treatment.

PMID- 23169508
TI  - Impact of cigarette smoking on cancer risk in the European prospective
      investigation into cancer and nutrition study.
AB  - PURPOSE: Our aim was to assess the impact of cigarette smoking on the risk of the
      tumors classified by the International Agency for Research on Cancer as causally
      associated with smoking, referred to as tobacco-related cancers (TRC). METHODS:
      The study population included 441,211 participants (133,018 men and 308,193
      women) from the European Prospective Investigation Into Cancer and Nutrition. We
      investigated 14,563 participants who developed a TRC during an average follow-up
      of 11 years. The impact of smoking cigarettes on cancer risk was assessed by the
      population attributable fraction (AF(p)), calculated using the adjusted hazard
      ratios and 95% CI for current and former smokers, plus either the prevalence of
      smoking among cancer cases or estimates from surveys in representative samples of
      the population in each country. RESULTS: The proportion of all TRC attributable
      to cigarette smoking was 34.9% (95% CI, 32.5 to 37.4) using the smoking
      prevalence among cases and 36.2% (95% CI, 33.7 to 38.6) using the smoking
      prevalence from the population. The AF(p) were above 80% for cancers of the lung
      and larynx, between 20% and 50% for most respiratory and digestive cancers and
      tumors from the lower urinary tract, and below 20% for the remaining TRC.
      CONCLUSION: Using data on cancer incidence for 2008 and our AF(p) estimates,
      about 270,000 new cancer diagnoses per year can be considered attributable to
      cigarette smoking in the eight European countries with available data for both
      men and women (Italy, Spain, United Kingdom, the Netherlands, Greece, Germany,
      Sweden, Denmark).

PMID- 23169509
TI  - Absolute risk prediction of second primary thyroid cancer among 5-year survivors
      of childhood cancer.
AB  - PURPOSE: We developed three absolute risk models for second primary thyroid
      cancer to assist with long-term clinical monitoring of childhood cancer
      survivors. PATIENTS AND METHODS: We used data from the Childhood Cancer Survivor
      Study (CCSS) and two nested case-control studies (Nordic CCSS; Late Effects Study
      Group). Model M1 included self-reported risk factors, model M2 added basic
      radiation and chemotherapy treatment information abstracted from medical records,
      and model M3 refined M2 by incorporating reconstructed radiation absorbed dose to
      the thyroid. All models were validated in an independent cohort of French
      childhood cancer survivors. RESULTS: M1 included birth year, initial cancer type,
      age at diagnosis, sex, and past thyroid nodule diagnosis. M2 added radiation
      (yes/no), radiation to the neck (yes/no), and alkylating agent (yes/no). Past
      thyroid nodule was consistently the strongest risk factor (M1 relative risk [RR],
      10.8; M2 RR, 6.8; M3 RR, 8.2). In the validation cohort, 20-year absolute risk
      predictions for second primary thyroid cancer ranged from 0.04% to 7.4% for M2.
      Expected events agreed well with observed events for each model, indicating good
      calibration. All models had good discriminatory ability (M1 area under the
      receiver operating characteristics curve [AUC], 0.71; 95% CI, 0.64 to 0.77; M2
      AUC, 0.80; 95% CI, 0.73 to 0.86; M3 AUC, 0.75; 95% CI, 0.69 to 0.82). CONCLUSION:
      We developed and validated three absolute risk models for second primary thyroid
      cancer. Model M2, with basic prior treatment information, could be useful for
      monitoring thyroid cancer risk in childhood cancer survivors.

PMID- 23169510
TI  - Adaptive trials in the neoadjuvant setting: a model to safely tailor care while
      accelerating drug development.

PMID- 23169511
TI  - Moyamoya disease misdiagnosed as leptomeningeal metastases.

PMID- 23169512
TI  - Advocates' perspective: neoadjuvant chemotherapy for breast cancer.

PMID- 23169513
TI  - Preoperative delays in the US Medicare population with breast cancer.
AB  - PURPOSE: Although no specific delay threshold after diagnosis of breast cancer
      has been demonstrated to affect outcome, delays can cause anxiety, and surgical
      waiting time has been suggested as a quality measure. This study was performed to
      determine the interval from presentation to surgery in Medicare patients with
      nonmetastatic invasive breast cancer who did not receive neoadjuvant chemotherapy
      and factors associated with a longer time to surgery. METHODS: Medicare claims
      linked to Surveillance, Epidemiology, and End Results data were reviewed for
      factors associated with delay between the first physician claim for a breast
      problem and first therapeutic surgery. RESULTS: Between 1992 and 2005, 72,586
      Medicare patients with breast cancer had a median interval (delay) between first
      physician visit and surgery of 29 days, increasing from 21 days in 1992 to 32
      days in 2005. Women (29 days v 24 days for men; P < .001), younger patients (29
      days; P < .001), blacks and Hispanics (each 37 days; P < .001), patients in the
      northeast (33 days; P < .001), and patients in large metropolitan areas (32 days;
      P < .001) had longer delays. Patients having breast conservation and mastectomies
      had adjusted median delays of 28 and 30 days, respectively, with simultaneous
      reconstruction adding 12 days. Preoperative components, including imaging
      modalities, biopsy type, and clinician visits, were also each associated with a
      specific additional delay. CONCLUSION: Waiting times for breast cancer surgery
      have increased in Medicare patients, and measurable delays are associated with
      demographics and preoperative evaluation components. If such increases continue,
      periodic assessment may be required to rule out detrimental effects on outcomes.

PMID- 23169514
TI  - Multimodal magnetic resonance imaging and 18F-L-dihydroxyphenylalanine positron
      emission tomography in early characterization of pseudoresponse and nonenhancing
      tumor progression in a pediatric patient with malignant transformation of
      ganglioglioma treated with bevacizumab.

PMID- 23169516
TI  - Gastric perforation secondary to regression of lung adenocarcinoma after
      gefitinib treatment.

PMID- 23169515
TI  - Prognostic impact of pregnancy after breast cancer according to estrogen receptor
      status: a multicenter retrospective study.
AB  - PURPOSE: We questioned the impact of pregnancy on disease-free survival (DFS) in
      women with history of breast cancer (BC) according to estrogen receptor (ER)
      status. PATIENTS AND METHODS: A multicenter, retrospective cohort study in which
      patients who became pregnant any time after BC were matched (1:3) to patients
      with BC with similar ER, nodal status, adjuvant therapy, age, and year of
      diagnosis. To adjust for guaranteed time bias, each nonpregnant patient had to
      have a disease-free interval at least equal to the time elapsing between BC
      diagnosis and date of conception of the matched pregnant one. The primary
      objective was DFS in patients with ER-positive BC. DFS in the ER-negative cohort,
      whole population, and overall survival (OS) were secondary objectives. Subgroup
      analyses included DFS according to pregnancy outcome and BC-pregnancy interval.
      With a two-sided alpha = 5% and beta = 20%, 645 ER-positive patients were
      required to detect a hazard ratio (HR) = 0.65. RESULTS: A total of 333 pregnant
      patients and 874 matched nonpregnant patients were analyzed, of whom 686 patients
      had an ER-positive disease. No difference in DFS was observed between pregnant
      and nonpregnant patients in the ER-positive (HR = 0.91; 95% CI, 0.67 to 1.24, P =
      .55) or the ER-negative (HR = 0.75; 95% CI, 0.51 to 1.08, P = .12) cohorts.
      However, the pregnant group had better OS (HR = 0.72; 95% CI, 0.54 to 0.97, P =
      .03), with no interaction according to ER status (P = .11). Pregnancy outcome and
      BC-pregnancy interval did not seem to impact the risk of relapse. CONCLUSION:
      Pregnancy after ER-positive BC does not seem to reduce the risk of BC recurrence.

PMID- 23169517
TI  - Cabozantinib in patients with advanced prostate cancer: results of a phase II
      randomized discontinuation trial.
AB  - PURPOSE: Cabozantinib (XL184) is an orally bioavailable tyrosine kinase inhibitor
      with activity against MET and vascular endothelial growth factor receptor 2. We
      evaluated the activity of cabozantinib in patients with castration-resistant
      prostate cancer (CRPC) in a phase II randomized discontinuation trial with an
      expansion cohort. PATIENTS AND METHODS: Patients received 100 mg of cabozantinib
      daily. Those with stable disease per RECIST at 12 weeks were randomly assigned to
      cabozantinib or placebo. Primary end points were objective response rate at 12
      weeks and progression-free survival (PFS) after random assignment. RESULTS: One
      hundred seventy-one men with CRPC were enrolled. Random assignment was halted
      early based on the observed activity of cabozantinib. Seventy-two percent of
      patients had regression in soft tissue lesions, whereas 68% of evaluable patients
      had improvement on bone scan, including complete resolution in 12%. The objective
      response rate at 12 weeks was 5%, with stable disease in 75% of patients. Thirty
      one patients with stable disease at week 12 were randomly assigned. Median PFS
      was 23.9 weeks (95% CI, 10.7 to 62.4 weeks) with cabozantinib and 5.9 weeks (95%
      CI, 5.4 to 6.6 weeks) with placebo (hazard ratio, 0.12; P < .001). Serum total
      alkaline phosphatase and plasma cross-linked C-terminal telopeptide of type I
      collagen were reduced by >= 50% in 57% of evaluable patients. On retrospective
      review, bone pain improved in 67% of evaluable patients, with a decrease in
      narcotic use in 56%. The most common grade 3 adverse events were fatigue (16%),
      hypertension (12%), and hand-foot syndrome (8%). CONCLUSION: Cabozantinib has
      clinical activity in men with CRPC, including reduction of soft tissue lesions,
      improvement in PFS, resolution of bone scans, and reductions in bone turnover
      markers, pain, and narcotic use.

PMID- 23169519
TI  - Challenges in recognizing treatment-related neuroendocrine prostate cancer.

PMID- 23169518
TI  - High-dose vincristine sulfate liposome injection for advanced, relapsed, and
      refractory adult Philadelphia chromosome-negative acute lymphoblastic leukemia.
AB  - PURPOSE: Relapsed adult acute lymphoblastic leukemia (ALL) is associated with
      high reinduction mortality, chemotherapy resistance, and rapid progression
      leading to death. Vincristine sulfate liposome injection (VSLI), sphingomyelin
      and cholesterol nanoparticle vincristine (VCR), facilitates VCR dose
      intensification and densification plus enhances target tissue delivery. We
      evaluated high-dose VSLI monotherapy in adults with Philadelphia chromosome (Ph) 
      negative ALL that was multiply relapsed, relapsed and refractory to reinduction,
      and/or relapsed after hematopoietic cell transplantation (HCT). PATIENTS AND
      METHODS: Sixty-five adults with Ph-negative ALL in second or greater relapse or
      whose disease had progressed following two or more leukemia therapies were
      treated in this pivotal phase II, multinational trial. Intravenous VSLI 2.25
      mg/m(2), without dose capping, was administered once per week until response,
      progression, toxicity, or pursuit of HCT. The primary end point was achievement
      of complete response (CR) or CR with incomplete hematologic recovery (CRi).
      RESULTS: The CR/CRi rate was 20% and overall response rate was 35%. VSLI
      monotherapy was effective as third-, fourth-, and fifth-line therapy and in
      patients refractory to other single- and multiagent reinduction therapies. Median
      CR/CRi duration was 23 weeks (range, 5 to 66 weeks); 12 patients bridged to a
      post-VSLI HCT, and five patients were long-term survivors. VSLI was generally
      well tolerated and associated with a low 30-day mortality rate (12%). CONCLUSION:
      High-dose VSLI monotherapy resulted in meaningful clinical outcomes including
      durable responses and bridging to HCT in advanced ALL settings. The toxicity
      profile of VSLI was predictable, manageable, and comparable to standard VCR
      despite the delivery of large, normally unachievable, individual and cumulative
      doses of VCR.

PMID- 23169520
TI  - Use of radiation therapy in the last 30 days of life among a large population
      based cohort of elderly patients in the United States.
AB  - PURPOSE: Our goal was to evaluate use and associated costs of radiation therapy
      (RT) in the last month of life among those dying of cancer. METHODS: We used the
      Surveillance, Epidemiology, and End Results (SEER) -Medicare linked databases to
      analyze claims data for 202,299 patients dying as a result of lung, breast,
      prostate, colorectal, and pancreas cancers from 2000 to 2007. Logistic regression
      modeling was used to conduct adjusted analyses of potential impacts of
      demographic, health services, and treatment-related variables on receipt of RT
      and treatment with greater than 10 days of RT. Costs were calculated in 2009
      dollars. RESULTS: Among the 15,287 patients (7.6%) who received RT in the last
      month of life, its use was associated with nonclinical factors such as race,
      gender, income, and hospice care. Of these patients, 2,721 (17.8%) received more
      than 10 days of treatment. Nonclinical factors that were associated with greater
      likelihood of receiving more than 10 days of RT in the last 30 days of life
      included: non-Hispanic white race, no receipt of hospice care, and treatment in a
      freestanding, versus a hospital-associated facility. Hospice care was associated
      with 32% decrease in total costs of care in the last month of life among those
      receiving RT. CONCLUSION: Although utilization of RT overall was low, almost one
      in five of patients who received RT in their final 30 days of life spent more
      than 10 of those days receiving treatment. More research is needed into physician
      decision making regarding use of RT for patients with end-stage cancer.

PMID- 23169521
TI  - Effect on survival of longer intervals between confirmed diagnosis and treatment
      initiation among low-income women with breast cancer.
AB  - PURPOSE: To determine the impact of longer periods between biopsy-confirmed
      breast cancer diagnosis and the initiation of treatment (Dx2Tx) on survival.
      PATIENTS AND METHODS: This study was a noninterventional, retrospective analysis
      of adult female North Carolina Medicaid enrollees diagnosed with breast cancer
      from January 1, 2000, through December, 31, 2002, in the linked North Carolina
      Central Cancer Registry-Medicaid Claims database. Follow-up data were available
      through July 31, 2006. Cox proportional hazards regression models were
      constructed to evaluate the impact on survival of delaying treatment >= 60 days
      after a confirmed diagnosis of breast cancer. RESULTS: The study cohort consisted
      of 1,786 low-income, adult women with a mean age of 61.6 years. A large
      proportion of the patients (44.3%) were racial minorities. Median time from
      biopsy-confirmed diagnosis to treatment initiation was 22 days. Adjusted Cox
      proportional hazards regression showed that although Dx2Tx length did not affect
      survival among those diagnosed at early stage, among late-stage patients,
      intervals between diagnosis and first treatment >= 60 days were associated with
      significantly worse overall survival (hazard ratio [HR], 1.66; 95% CI, 1.00 to
      2.77; P = .05) and breast cancer-specific survival (HR, 1.85; 95% CI, 1.04 to
      3.27; P = .04). CONCLUSION: One in 10 women waited >= 60 days to initiate
      treatment after a diagnosis of breast cancer. Waiting >= 60 days to initiate
      treatment was associated with a significant 66% and 85% increased risk of overall
      and breast cancer-related death, respectively, among late-stage patients.
      Interventions designed to increase the timeliness of receiving breast cancer
      treatments should target late-stage patients, and clinicians should strive to
      promptly triage and initiate treatment for patients diagnosed at late stage.

PMID- 23169522
TI  - Diagnosis of primary CNS melanoma with neuroimaging.

PMID- 23169524
TI  - Cooperative supramolecular polymerization: comparison of different models applied
      on the self-assembly of bis(merocyanine) dyes.
AB  - Three new molecular building blocks 1 a-c for supramolecular polymerization are
      described that feature two dipolar merocyanine dyes tethered by p-xylylene
      spacers. Concentration- and temperature-dependent UV/Vis spectroscopy in
      chloroform combined with dynamic light scattering, capillary viscosimetry and
      atomic force microscopy investigations were applied to elucidate the mechanistic
      features of the self-assembly of these strongly dipolar dyes. Our detailed
      studies reveal that the self-assembly is very pronounced for bis(merocyanines) 1
      a,b bearing linear alkyl chains, but completely absent for bis(merocyanine) 1 c
      bearing sterically more bulky ethylhexyl substituents. Both temperature- and
      concentration-dependent UV/Vis data provide unambiguous evidence for a
      cooperative self-assembly process for bis(merocyanines) 1 a,b, which was analyzed
      in detail by the Meijer-Schenning-Van-der-Schoot model (applicable to temperature
      dependent data) and by the Goldstein-Stryer model (applicable to concentration
      dependent data). By combining both methods all parameters of interest to
      understand the self-assembly process could be derived, including in particular
      the nucleus size (8-10 monomeric units), the cooperativity factor (ca. 0.006),
      and the nucleation and elongation constants of about 10(3)  and 10(6)  M(-1)  in
      chloroform at room temperature, respectively.

PMID- 23169523
TI  - Parenteral hydration in patients with advanced cancer: a multicenter, double
      blind, placebo-controlled randomized trial.
AB  - PURPOSE: The vast majority of patients with cancer at the end of life receive
      parenteral hydration in hospitals and no hydration in hospice, with limited
      evidence supporting either practice. In this randomized controlled trial, we
      determined the effect of hydration on symptoms associated with dehydration,
      quality of life, and survival in patients with advanced cancer. PATIENTS AND
      METHODS: We randomly assigned 129 patients with cancer from six hospices to
      receive parenteral hydration (normal saline 1 L per day) or placebo (normal
      saline 100 mL per day) daily over 4 hours. The primary outcome was change in the
      sum of four dehydration symptoms (fatigue, myoclonus, sedation and
      hallucinations, 0 = best and 40 = worst possible) between day 4 and baseline.
      Secondary outcomes included Edmonton Symptom Assessment Scale (ESAS), Memorial
      Delirium Assessment Scale (MDAS), Nursing Delirium Screening Scale (NuDESC),
      Unified Myoclonus Rating Scale (UMRS), Functional Assessment of Chronic Illness
      Therapy-Fatigue (FACIT-F), Dehydration Assessment Scale, creatinine, urea, and
      overall survival. Intention-to-treat analysis was conducted to examine the change
      by day 4 +/- 2 and day 7 +/- 2 between groups. RESULTS: The hydration (n = 63)
      and placebo (n = 66) groups had similar baseline characteristics. We found no
      significant differences between the two groups for change in the sum of four
      dehydration symptoms (-3.3 v -2.8, P = .77), ESAS (all nonsignificant), MDAS (1 v
      3.5, P = .084), NuDESC (0 v 0, P = .13), and UMRS (0 v 0, P = .54) by day 4.
      Results for day 7, including FACIT-F, were similar. Overall survival did not
      differ between the two groups (median, 21 v 15 days, P = .83). CONCLUSION:
      Hydration at 1 L per day did not improve symptoms, quality of life, or survival
      compared with placebo.

PMID- 23169525
TI  - Respiratory impedance and bronchodilator responsiveness in healthy children aged
      2-13 years.
AB  - BACKGROUND: The forced oscillation technique (FOT) can be used in children as
      young as 2 years of age and in those unable to perform routine spirometry. There
      is limited information on changes in FOT outcomes in healthy children beyond the
      preschool years and the level of bronchodilator responsiveness (BDR) in healthy
      children. We aimed to create reference ranges for respiratory impedance outcomes
      collated from multiple centers. Outcomes included respiratory system resistance
      (R(rs)) and reactance (X(rs)), resonant frequency (Fres), frequency dependence of
      R(rs) (Fdep), and the area under the reactance curve (AX). We also aimed to
      define the physiological effects of bronchodilators in a large population of
      healthy children using the FOT. METHODS: Respiratory impedance was measured in
      760 healthy children, aged 2-13 years, from Australia and Italy. Stepwise linear
      regression identified anthropometric predictors of transformed R(rs) and X(rs) at
      6, 8, and 10 Hz, Fres, Fdep, and AX. Bronchodilator response (BDR) was assessed
      in 508 children after 200 ug of inhaled salbutamol. RESULTS: Regression analysis
      showed that R(rs), X(rs), and AX outcomes were dependent on height and sex. The
      BDR cut-offs by absolute change in R(rs8), X(rs8), and AX were -2.74 hPa s L(-1),
      1.93 hPa s L(-1), and -33 hPa s L(-1), respectively. These corresponded to
      relative and Z-score changes of -32%; -1.85 for R(rs8), 65%; 1.95 for X(rs8), and
      -82%; -2.04 for AX. CONCLUSIONS: We have established generalizable reference
      ranges for respiratory impedance and defined cut-offs for a positive
      bronchodilator response using the FOT in healthy children.

PMID- 23169528
TI  - The disulfide bond of an RGD4C motif inserted within the Hi loop of the
      adenovirus type 5 fiber protein is critical for retargeting to alphav -integrins.
AB  - BACKGROUND: The alpha(v) -integrin binding motif RGD4C (CDCRGDCFC) has been used
      extensively to circumvent inefficient adenovirus type 5 (Ad5) transduction of
      cells expressing low levels of the coxsackie and adenovirus receptor. However,
      until now, it has been unclear whether disulfide bonds in the RGD4C motif
      influence the retargeting potential of RGD4C-modified Ad5. METHODS: Replication
      deficient Ad5 bearing wild-type fiber (Ad5wt) or RGD4G, RGD4C and RGD2C2G
      insertions within the HI loop of the fiber protein (Ad5RGD4G, Ad5RGD4C and
      Ad5RGD2C2G, respectively) were used to transduce a panel of cancer cell lines,
      with or without previous treatment of these Ad5s with the reducing agent
      dithiothreitol (DTT). In parallel, native and DTT-treated fiber proteins isolated
      from purified Ad5RGD4C were compared by mass spectrometry. RESULTS: Ad5RGD4C
      transduced all studied cell lines much more efficiently than Ad5wt, whereas
      Ad5RGD4G transduced cells only slightly more efficiently than Ad5wt. DTT
      treatment had no effect on cell transduction by wild-type Ad5wt and Ad5RGD4G but
      abolished the increased transduction efficacy of Ad5RGD4C in a dose-dependent
      manner. The mass spectra of native and DTT-reduced tryptic digests of the
      Ad5RGD4C fiber protein are consistent with the presence of a C(547) -C(549)
      linkage in the C(547) DC(549) RGDC(553) FC(555) motif. Finally, the high
      transduction efficacy of Ad5RGD4C is conserved in Ad5RGD2C2G. CONCLUSIONS: We
      provide genetic and biochemical data strongly suggesting that cysteines C(547)
      and C(549) from the C(547) DC(549) RGDC(553) FC(555) motif inserted in the HI
      loop of the Ad5 fiber form a single disulfide bond, with this disulfide bond
      being crucial for Ad5RGD4C retargeting to av-integrins.

PMID- 23169529
TI  - Amyloid toxicity and platelet-activating factor signaling.
AB  - Amyloidosis is the accumulation of insoluble proteinaceous aggregates in vivo and
      is implicated in many neurodegenerative diseases, including Alzheimer's,
      Huntington's, and Parkinson's diseases. This article briefly reviews the current
      knowledge of amyloid aggregate toxicity and inflammatory signaling in the nervous
      system. In particular, we focus our attention on the role of platelet-activating
      factor (PAF) as mediator of amyloid cytotoxicity.

PMID- 23169530
TI  - Novel mutations in the gene encoding very long-chain acyl-CoA dehydrogenase
      identified in patients with partial carnitine palmitoyltransferase II deficiency.
AB  - INTRODUCTION: Twenty-six patients with clinical symptoms of adult onset carnitine
      palmitoyltransferase II (CPTII) deficiency were examined. All patients had
      skeletal muscle CPTII enzyme activity levels indicative of heterozygosity for
      CPT2 mutations, however sequence analysis identified no pathogenic mutations
      within the CPT2 gene. METHODS: Because the reaction product of CPTII is the
      substrate for very long-chain acyl-CoA dehydrogenase (VLCAD), we examined the
      ACADVL gene in these patients by sequence analysis. RESULTS: Missense mutations
      within the ACADVL gene were identified in 3 of the patients. CONCLUSIONS: The
      locations of the altered amino acid residues within the crystal structure of
      VLCAD are on the surface of the molecule and may be involved in interactions with
      neighboring molecules. These findings support the importance of considering that
      mutations may be present in the ACADVL gene when a significant partial deficiency
      is found in CPTII activity, but no mutations in the CPT2 gene can be identified.

PMID- 23169527
TI  - The beta-catenin destruction complex.
AB  - The Wnt/beta-catenin pathway is highly regulated to insure the correct temporal
      and spatial activation of its target genes. In the absence of a Wnt stimulus, the
      transcriptional coactivator beta-catenin is degraded by a multiprotein
      "destruction complex" that includes the tumor suppressors Axin and adenomatous
      polyposis coli (APC), the Ser/Thr kinases GSK-3 and CK1, protein phosphatase 2A
      (PP2A), and the E3-ubiquitin ligase beta-TrCP. The complex generates a beta-TrCP
      recognition site by phosphorylation of a conserved Ser/Thr-rich sequence near the
      beta-catenin amino terminus, a process that requires scaffolding of the kinases
      and beta-catenin by Axin. Ubiquitinated beta-catenin is degraded by the
      proteasome. The molecular mechanisms that underlie several aspects of destruction
      complex function are poorly understood, particularly the role of APC. Here we
      review the molecular mechanisms of destruction complex function and discuss
      several potential roles of APC in beta-catenin destruction.

PMID- 23169531
TI  - Co-motif discovery identifies an Esrrb-Sox2-DNA ternary complex as a mediator of
      transcriptional differences between mouse embryonic and epiblast stem cells.
AB  - Transcription factors (TF) often bind in heterodimeric complexes with each TF
      recognizing a specific neighboring cis element in the regulatory region of the
      genome. Comprehension of this DNA motif grammar is opaque, yet recent
      developments have allowed the interrogation of genome-wide TF binding sites. We
      reasoned that within this data novel motif grammars could be identified that
      controlled distinct biological programs. For this purpose, we developed a novel
      motif-discovery tool termed fexcom that systematically interrogates ChIP-seq data
      to discover spatially constrained TF-TF composite motifs occurring over short DNA
      distances. We applied this to the extensive ChIP-seq data available from mouse
      embryonic stem cells (ESCs). In addition to the well-known and most prevalent sox
      oct motif, we also discovered a novel constrained spacer motif for Esrrb and Sox2
      with a gap of between 2 and 8 bps that Essrb and Sox2 cobind in a selective
      fashion. Through the use of knockdown experiments, we argue that the Esrrb-Sox2
      complex is an arbiter of gene expression differences between ESCs and epiblast
      stem cells (EpiSC). A number of genes downregulated upon dual Esrrb/Sox2
      knockdown (e.g., Klf4, Klf5, Jam2, Pecam1) are similarly downregulated in the ESC
      to EpiSC transition and contain the esrrb-sox motif. The prototypical Esrrb-Sox2
      target gene, containing an esrrb-sox element conserved throughout eutherian and
      metatherian mammals, is Nr0b1. Through positive regulation of this
      transcriptional repressor, we argue the Esrrb-Sox2 complex promotes the ESC state
      through inhibition of the EpiSC transcriptional program and the same trio may
      also function to maintain trophoblast stem cells.

PMID- 23169532
TI  - High-contrast fluorescence sensing of aqueous Cu(I) with triarylpyrazoline
      probes: dissecting the roles of ligand donor strength and excited state proton
      transfer.
AB  - Cu(I)-responsive fluorescent probes based on a photoinduced electron transfer
      (PET) mechanism generally show incomplete fluorescence recovery relative to the
      intrinsic quantum yield of the fluorescence reporter. Previous studies on probes
      with an N-aryl thiazacrown Cu(I)-receptor revealed that the recovery is
      compromised by incomplete Cu(I)-N coordination and resultant ternary complex
      formation with solvent molecules. Building upon a strategy that successfully
      increased the fluorescence contrast and quantum yield of Cu(I) probes in
      methanol, we integrated the arylamine PET donor into the backbone of a
      hydrophilic thiazacrown ligand with a sulfonated triarylpyrazoline as a water
      soluble fluorescence reporter. This approach was not only expected to disfavor
      ternary complex formation in aqueous solution but also to maximize PET switching
      through a synergistic Cu(I)-induced conformational change. The resulting water
      soluble probe 1 gave a strong 57-fold fluorescence enhancement upon saturation
      with Cu(I) with high selectivity over other cations, including Cu(II), Hg(II),
      and Cd(II); however, the recovery quantum yield did not improve over probes with
      the original N-aryl thiazacrown design. Concluding from detailed photophysical
      data, including responses to acidification, solvent isotope effects, quantum
      yields, and time-resolved fluorescence decay profiles, the fluorescence contrast
      of 1 is compromised by inadequate coordination of Cu(I) to the weakly basic
      arylamine nitrogen of the PET donor and by fluorescence quenching via two
      distinct excited state proton transfer pathways operating under neutral and
      acidic conditions.

PMID- 23169533
TI  - Characterization of direct antiglobulin test-negative autoimmune hemolytic
      anemia: a study of 154 cases.
AB  - Direct antiglobulin test (DAT)-negative (DAT-)autoimmune hemolytic anemia (AIHA)
      is empirically thought to show the same clinical conditions as DAT-positive
      (DAT+)AIHA, with the exception of an adequate amount of red blood cell (RBC)
      bound immunoglobulin (Ig)G. We investigated the clinical characteristics of DAT
      AIHA in comparison with DAT+AIHA. Of the 582 patients referred to our laboratory
      with undiagnosed hemolytic anemia, AIHA was clinically diagnosed in 216 patients
      (DAT-AIHA, n = 154; DAT+AIHA, n = 62). The percentage of reticulocytes, mean
      corpuscular volume, RBC-IgG levels, white blood cell count, and total protein
      (TP) levels were significantly higher in patients with DAT+AIHA than patients
      with DAT-AIHA. The hemoglobin level was significantly lower in patients with
      DAT+AIHA. No significant differences between patients with DAT-AIHA and DAT+AIHA
      existed with respect to age, gender, idiopathic/secondary nature, complications
      such as Evans syndrome, effectiveness of steroid treatment, or survival rate at 1
      year following diagnosis. Patients with DAT-AIHA required significantly lower
      doses of steroids for maintenance therapy. Based on multivariate analysis of
      idiopathic DAT-AIHA (n = 110), TP and Evans syndrome were associated with the
      effectiveness of steroids (adjusted odds ratio [aOR], 1.36/[0.1 g/dl]; 95%
      confidence interval [CI], 1.01-1.84) and survival at the 1-year follow-up (aOR,
      0.1; 95% CI, 0.01-0.88). Our results indicate that patients with DAT-AIHA
      generally suffer milder anemia and hemolysis than patients with DAT+AIHA, respond
      equally well to steroids, and have comparable survival at 1-year.

PMID- 23169534
TI  - Review of computerized physician handoff tools for improving the quality of
      patient care.
AB  - BACKGROUND: Computerized physician handoff tools (CHTs) are designed to allow
      distributed access and synchronous archiving of patient information via Internet
      protocols. However, their impact on the quality of physician handoff, patient
      care, and physician work efficiency have not been extensively analyzed. METHODS:
      We searched MEDLINE, PUBMED, EMBASE, CINAHL, the Cochrane database for systematic
      reviews, and the Cochrane central register for clinical trials, from January 1960
      to December 2011. We selected all articles that reported randomized controlled
      trials, controlled clinical trials, controlled before-after studies, and quasi
      experimental studies of the use of CHTs for physician handoff for hospitalized
      patients. Relevant studies were evaluated independently for their eligibility for
      inclusion by 2 individuals in a 2-stage process. RESULTS: The literature search
      identified 1026 citations of which 6 satisfied the inclusion criteria. One study
      was a randomized controlled trial, whereas 5 were controlled before-after
      studies. Two studies showed that using CHTs reduced adverse events and missing
      patients. Three studies demonstrated improved overall quality of handoff after
      CHT implementation. One study suggested that CHTs could potentially enhance work
      efficiency and continuity of care during physician handoff. Conflicting impacts
      on consistency of handoff were found in 2 studies. CONCLUSIONS: The evidence that
      CHTs improve physician handoff and quality of hospitalized patient care is
      limited. CHT may improve the efficiency of physician work, reduce adverse events,
      and increase the completeness of physician handoffs. However, further evaluation
      using rigorous study designs is needed.

PMID- 23169535
TI  - Phosphoglycerate mutase deficiency with tubular aggregates in a patient from
      Panama.
AB  - INTRODUCTION: Phosphoglycerate mutase deficiency (PGAM) is a rare metabolic
      myopathy that results in terminal block in glycogenolysis. Clinically, patients
      with PGAM deficiency are asymptomatic, except when they engage in brief,
      strenuous efforts, which may trigger myalgias, cramps, muscle necrosis, and
      myoglobinuria. An unusual pathologic feature of PGAM deficiency is the
      association with tubular aggregates. METHODS: We report an African-American
      patient from Panama with partial deficiency of PGAM who presented with
      asymptomatic elevation of creatine kinase levels and tubular aggregates on muscle
      biopsy. RESULTS: Muscle biopsies showed subsarcolemmal and sarcolemmal tubular
      aggregates in type 2 fibers. Muscle PGAM enzymatic activity was decreased and
      gene sequencing revealed a heterozygous mutation in codon 78 of exon 1 of the
      PGAM2 gene, which is located on the short arm of chromosome 7. CONCLUSIONS: PGAM
      deficiency has been reported in 14 patients, 9 of whom were of African-American
      ethnicity, and in 5 (36%) tubular aggregates were seen on muscle biopsy. Contrary
      to previously reported cases, our patient was initially asymptomatic. This
      further expands the PGAM deficiency phenotype.

PMID- 23169536
TI  - Clinical assessment is an accurate predictor of which patients will need
      septoplasty.
AB  - OBJECTIVES/HYPOTHESIS: Septoplasty is a frequently performed surgical procedure
      with the most common indication being nasal airway obstruction. Almost
      universally, health insurance companies mandate a trial of medical therapy
      consisting of intranasal corticosteroids prior to performance of septoplasty
      regardless of clinical assessment. Evidence for this requirement is lacking. We
      sought to evaluate the initial clinical assessment as a predictor of response to
      this mandated trial of medical treatment. STUDY DESIGN: Retrospective review of
      prospectively collected data on 137 consecutive patients who presented with
      symptoms of nasal obstruction and a deviated nasal septum on physical
      examination. METHODS: Patients were placed into one of three cohorts based on
      prediction of 1) failure of medical therapy with subsequent septoplasty, 2)
      success of medical therapy without subsequent septoplasty, or 3) unable to make a
      prediction. Patients from each cohort were assessed for subsequent response to
      medical therapy and ultimate need for septoplasty. RESULTS: Overall clinical
      assessment had a sensitivity of 86.9%, specificity of 91.8%, positive predictive
      value of 93.6%, and negative predictive value of 96.4% for detecting/predicting
      need for septoplasty. The accuracy of the overall clinical assessment is
      considerably better than severe deviation at any one septal anatomical site. Of
      patients whose response to medical therapy could not be predicted, 61.3% failed
      medical therapy and needed surgery; this is statistically equivalent to a 50/50
      distribution between either needing septoplasty or not. CONCLUSIONS: Clinical
      assessment at initial presentation of patients with nasal obstruction and
      deviated septum is highly accurate in predicting which patients will need
      septoplasty.

PMID- 23169539
TI  - Cognitive deficits are usually mild in patients with breast cancer after
      chemotherapy.

PMID- 23169538
TI  - A very low carbohydrate ketogenic diet prevents the progression of hepatic
      steatosis caused by hyperglycemia in a juvenile obese mouse model.
AB  - OBJECTIVE: To investigate whether the improvement in hyperglycemia by dietary
      control influences hyperglycemia-induced pathologies in tissues of juvenile obese
      (ob/ob) mice. DESIGN: Five-week-old ob/ob mice were fed a very low carbohydrate
      ketogenic diet (KD) for 7 weeks. The blood glucose levels and body weight were
      monitored during this period. Biochemical parameters in the serum and tissue
      pathologies of the mice were analyzed at the end of the 7-week period. RESULTS:
      The hyperglycemic phenotype of the ob/ob mice was improved by KD feeding for 7
      weeks. Surprisingly, we found that KD feeding also drastically reduced the
      hepatic steatosis phenotype in ob/ob mice, while their obesity phenotype was
      unaltered. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis
      revealed that several proteins found in the liver of ob/ob mice fed a regular
      chow diet were undetectable after being fed KD. Liquid chromatography with tandem
      mass spectrometry (LC-MS/MS) MASCOT search and western blot analysis revealed
      that the proteins absent from the mice fed KD included fatty acid synthase (FAS)
      and acetyl-CoA carboxylase 1 (ACC1), which are key enzymes for lipogenesis in the
      liver. Fatty acid analysis supported the results because the ratio of C18:1,
      which is a major product of lipogenesis, was reduced by KD feeding. However,
      C18:2, which cannot be synthesized in mammalian cells but is present in the KD,
      was found to be a major component in the liver of KD-fed ob/ob mice. CONCLUSION:
      Hyperglycemia promotes hepatic steatosis via the lipogenic pathway in the liver
      of juvenile ob/ob mice. However, the development of steatosis is prevented by
      feeding KD owing to an improvement in hyperglycemia. We found that the
      progression of steatosis is reflected by the composition of fatty acids in the
      total lipids of the liver and serum.

PMID- 23169537
TI  - Stem cell function during plant vascular development.
AB  - The plant vascular system, composed of xylem and phloem, evolved to connect plant
      organs and transport various molecules between them. During the post-embryonic
      growth, these conductive tissues constitutively form from cells that are derived
      from a lateral meristem, commonly called procambium and cambium.
      Procambium/cambium contains pluripotent stem cells and provides a
      microenvironment that maintains the stem cell population. Because vascular plants
      continue to form new tissues and organs throughout their life cycle, the
      formation and maintenance of stem cells are crucial for plant growth and
      development. In this decade, there has been considerable progress in
      understanding the molecular control of the organization and maintenance of stem
      cells in vascular plants. Noticeable advance has been made in elucidating the
      role of transcription factors and major plant hormones in stem cell maintenance
      and vascular tissue differentiation. These studies suggest the shared regulatory
      mechanisms among various types of plant stem cell pools. In this review, we focus
      on two aspects of stem cell function in the vascular cambium, cell proliferation
      and cell differentiation.

PMID- 23169540
TI  - Preparation and characterization of carbon nano-onion/PEDOT:PSS composites.
AB  - Composites of unmodified or oxidized carbon nano-onions (CNOs/ox-CNOs) with
      poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) are prepared
      with different compositions. By varying the ratio of PEDOT:PSS relative to CNOs,
      CNO/PEDOT:PSS composites with various PEDOT:PSS loadings are obtained and the
      corresponding film properties are studied as a function of the polymer. X-ray
      photoelectron spectroscopy characterization is performed for pristine and ox-CNO
      samples. The composites are characterized by scanning and transmission electron
      microscopy and differential scanning calorimetry studies. The electrochemical
      properties of the nanocomposites are determined and compared. Doping the
      composites with carbon nanostructures significantly increases their mechanical
      and electrochemical stabilities. A comparison of the results shows that CNOs
      dispersed in the polymer matrices increase the capacitance of the CNO/PEDOT:PSS
      and ox-CNO/PEDOT:PSS composites.

PMID- 23169542
TI  - Thiol-directed synthesis of highly fluorescent gold clusters and their conversion
      into stable imaging nanoprobes.
AB  - Fluorescent gold clusters (FGCs) with tunable emission from blue to red and
      quantum yields in the range of 6-17% have been synthesized by simple modification
      of the conditions used for the synthesis of gold nanoparticles, namely by
      replacing the stronger reducing agent with a controlled amount of thiol. Various
      functional FGCs with hydrodynamic diameters of 5-12 nm have been successfully
      synthesized and used as cell labels. The results of our investigations strongly
      indicate that FGCs composed of Au(0) are more stable imaging probes than commonly
      reported red/NIR-emitting FGCs with a composition of Au(0)/Au(I), as this
      combination rapidly transforms into nonfluorescent large clusters on exposure to
      light. The FGC-based nanoprobes reported herein exhibit stable fluorescence upon
      continuous light exposure and can be used as imaging probes with low
      cytotoxicity.

PMID- 23169545
TI  - Inhaled foreign bodies in children: a global perspective on their
      epidemiological, clinical, and preventive aspects.
AB  - CONTEXT: While several articles describe clinical management of foreign bodies
      injuries in the upper air tract, little epidemiological evidence is available
      from injury databases. OBJECTIVE: This article aims to understand the burden of
      airway FB injuries in high-, low-, and middle-income countries as emerging from
      scientific literature. DATA SOURCES: One thousand six hundred ninety-nine
      published articles 1978-2008. STUDY SELECTION: A free text search on PubMed
      database ((foreign bodies) or (foreign body)) and ((aspiration) or (airways) or
      (tracheobronchial) or (nasal) or (inhalation) or (obstruction) or (choking) or
      (inhaled) or (aspirations) or (nose) or (throat) or (asphyxiation)) and
      ((children) or (child)). DATA EXTRACTION: Information on reported injuries
      according to country, time period, children sex and age, FB type, site of
      obstruction, symptoms, signs, diagnostic and therapeutic procedures, delay at the
      diagnosis, complications, number of deaths. RESULTS: Serious complications occur
      both in high-income and low-middle income countries in a considerable proportion
      of cases (10% and 20%, respectively). Similarly, death is not infrequent (5-7% of
      cases). CONCLUSIONS: Few countries have good systematic data collection and
      there's a lack of sensibility in parents and clinicians in terms of acknowledge
      of the choking risk. On the contrary, international surveillance systems able to
      collect information in a standardized way need to be implemented.

PMID- 23169546
TI  - Synthesis and chemistry of bis(triisopropylphosphine) nickel(I) and nickel(0)
      precursors.
AB  - High yield syntheses of ((i)Pr(3)P)(2)NiX (3a-c), (where X = Cl, Br, I) were
      established by comproportionation of ((i)Pr(3)P)(2)NiX(2) (1a-c) with
      ((i)Pr(3)P)(2)Ni(eta(2)-C(2)H(4)) (2). Reaction of 1a with either NaH or
      LiHBEt(3) provided ((i)Pr(3)P)(2)NiHCl (4), along with 3a as a side-product.
      Reduction of ((i)Pr(3)P)(2)NiCl (3a-c) with Mg in presence of nitrogen saturated
      THF solutions provided the dinitrogen complex [((i)Pr(3)P)(2)Ni](2)(MU
      eta(1):eta(1)-N(2)) (5). In aromatic solvents such as benzene and toluene a
      thermal equilibrium exists between 5 and the previously reported monophosphine
      solvent adducts ((i)Pr(3)P)Ni(eta(6)-arene) (6a,b). Reaction of 5 with carbon
      dioxide provided ((i)Pr(3)P)(2)Ni(eta(2)-CO(2)) (7). Thermolysis of 9 at 60 
      degrees C provided a mixture of products that included the reduction product
      ((i)Pr(3)P)(2)Ni(CO)(2) (8) along with (i)Pr(3)P=O, as identified by NMR
      spectroscopy. Complex 8 was also prepared in high yield from the reaction of 5
      with CO. Reaction of 5 with CS(2) gave the dimeric carbon disulfide complex
      [((i)Pr(3)P)Ni(MU-eta(1):eta(2)-CS(2))](2) (9). Diphenylphosphine reacts with 5
      to form the dinuclear Ni(I) complex [((i)Pr(3)P)Ni(MU(2)-PPh(2))](2) (10).
      Complex 5 reacts with PhSH to form ((i)Pr(3)P)(2)Ni(SPh)(H) (11), which slowly
      loses H(2) and (i)Pr(3)P to form the dimeric Ni(I) complex [((i)Pr(3)P)Ni(MU(2)
      SPh)](2) (12) at room temperature. Complex 12 was also accessed by salt
      metathesis from the reaction of ((i)Pr(3)P)(2)NiCl (3a) with PhSLi, which
      demonstrates the utility of 3a as a Ni(I) precursor. With the exception of 6a,b,
      all compounds were structurally characterized by single-crystal X-ray
      crystallography.

PMID- 23169547
TI  - RUNX2 in mammary gland development and breast cancer.
AB  - Runx2 is best known as an essential factor in osteoblast differentiation and bone
      development but, like many other transcription factors involved in development,
      is known to operate over a much wider tissue range. Our understanding of these
      other aspects of Runx2 function is still at a relatively early stage and the
      importance of its role in cell fate decisions and lineage maintenance in non
      osseous tissues is only beginning to emerge. One such tissue is the mammary
      gland, where Runx2 is known to be expressed and participate in the regulation of
      mammary specific genes. Furthermore, differential and temporal expression of this
      gene is observed during mammary epithelial differentiation in vivo, strongly
      indicative of an important functional role. Although the precise nature of that
      role remains elusive, preliminary evidence hints at possible involvement in the
      regulation of mammary stem and/or progenitor cells. As with many genes important
      in regulating cell fate, RUNX2 has also been linked to metastatic cancer where in
      some established breast cell lines, retention of expression is associated with a
      more invasive phenotype. More recently, expression analysis has been extended to
      primary breast cancers where high levels of RUNX2 align with a specific subtype
      of the disease. That RUNX2 expression correlates with the so called "Triple
      Negative" subtype is particularly interesting given the known cross talk between
      Runx2 and estrogen receptor signaling pathways. This review summaries our current
      understanding of Runx2 in mammary gland development and cancer, and postulates a
      role that may link both these processes.

PMID- 23169551
TI  - Tumor-associated macrophages regulate murine breast cancer stem cells through a
      novel paracrine EGFR/Stat3/Sox-2 signaling pathway.
AB  - The cancer stem cell (CSC) hypothesis has gained significant recognition as a
      descriptor of tumorigenesis. Additionally, tumor-associated macrophages (TAMs)
      are known to promote growth and metastasis of breast cancer. However, it is not
      known whether TAMs mediate tumorigenesis through regulation of breast CSCs. Here,
      we report that TAMs promote CSC-like phenotypes in murine breast cancer cells by
      upregulating their expression of Sox-2. These CSC-like phenotypes were
      characterized by increased Sox-2, Oct-4, Nanog, AbcG2, and Sca-1 gene expression,
      in addition to increased drug-efflux capacity, resistance to chemotherapy, and
      increased tumorigenicity in vivo. Downregulation of Sox-2 in tumor cells by siRNA
      blocked the ability of TAMs to induce these CSC-like phenotypes and inhibited
      tumor growth in vivo. Furthermore, we identified a novel epidermal growth factor
      receptor (EGFR)/signal transducers and activators of transcription 3 (Stat3)/Sox
      2 paracrine signaling pathway between macrophages and mouse breast cancer cells
      that is required for macrophage-induced upregulation of Sox-2 and CSC phenotypes
      in tumor cells. We showed that this crosstalk was effectively blocked by the
      small molecule inhibitors AG1478 or CDDO-Im against EGFR and Stat3, respectively.
      Therefore, our report identifies a novel role for TAMs in breast CSC regulation
      and establishes a rationale for targeting the EGFR/Stat3/Sox-2 signaling pathway
      for CSC therapy.

PMID- 23169552
TI  - Female rats are relatively more sensitive to reduced lipid versus reduced
      carbohydrate availability.
AB  - OBJECTIVES: Because females have blunted counterregulatory responses to
      hypoglycemia relative to males, we hypothesized that females would have greater
      sensitivity to changes in lipid availability. DESIGN AND SUBJECTS: To assess
      this, we examined the feeding response to glucoprivation (2-deoxyglucose; 2DG)
      and lipoprivation (mercaptoacetate; MA) in age-matched male and female Long-Evans
      rats. RESULTS: Males versus females had significantly greater food intake after
      250 mg kg(-1) of 2DG, but there were no sex differences with the 750 mg kg(-1)
      dose of 2DG. Glucose responses to 250 mg kg(-1) of 2DG were also significantly
      greater in males versus females. In contrast, females had a significant increase
      in food intake with all doses of MA versus saline, and had significantly greater
      food intake compared with males at the lowest and highest doses of MA with a
      trend towards significance with the intermediate dose. To determine whether
      estradiol (E2) is the mechanism underlying this sexual dimorphism, ovariectomized
      females were injected with vehicle or 2 MUg of E2 every fourth day to mimic the
      variations in across the estrous cycle. Ovariectomized females significantly
      increased feeding and glucose after 250 mg kg(-1) of 2DG over intact females and
      E2 had no effect on these responses. Although the feeding response to 2DG was not
      different, the glucose response to 2DG was still significantly greater in males
      versus ovariectomies females. However, ovariectomized females also did not
      increase food intake after MA, regardless of E2 treatment. CONCLUSIONS: These
      data collectively suggest that males are relatively more sensitive to glucose
      deprivation and females are relatively more sensitive to lipid deprivation.
      Further, these data rule out a role for cyclic changes in E2 in these sex
      differences.

PMID- 23169553
TI  - Opportunity lost: end-of-life discussions in cancer patients who die in the
      hospital.
AB  - BACKGROUND: End-of-life discussions are associated with decreased use of life
      sustaining treatments in patients dying of cancer in the outpatient setting, but
      little is known about discussions that take place during terminal
      hospitalizations. OBJECTIVES: To determine the proportion of patients assessed by
      the clinical team to have decisional capacity on admission, how many of these
      patients participated or had a surrogate participate in a discussion about end-of
      life care, and whether patient participation was associated with treatments
      received. DESIGN: Retrospective review. SETTING: Inpatient. PATIENTS: Adult
      patients with advanced cancer who died in the hospital between January 1, 2004
      and December 31, 2007. RESULTS: Of the 145 inpatients meeting inclusion criteria,
      115 patients (79%) were documented to have decisional capacity on admission.
      Among these patients, 46 (40%) were documented to lose decisional capacity prior
      to an end-of-life discussion and had the discussion held instead by a surrogate.
      Patients who had surrogate participation in the end-of-life discussions were more
      likely to receive mechanical ventilation (56.5% vs 23.2%, P < 0.01), artificial
      nutrition (45.7% vs 25.0%, P = 0.03), chemotherapy (39.1% vs 5.4%, P <0.01), and
      intensive care unit (ICU) treatment (56.5% vs 23.2%, P <0.01) compared to
      patients who participated in discussions. There was no difference between
      palliative treatments received. CONCLUSION: The majority of patients with
      advanced cancer are considered to have decisional capacity at the time of their
      terminal hospitalization. Many lose decisional capacity before having an end-of
      life discussion and have surrogate decision-makers participate in these
      discussions. These patients received more aggressive life-sustaining treatments
      prior to death and represent a missed opportunity to improve end-of-life care.

PMID- 23169554
TI  - Reasons for using swelling ratio in sonographic diagnosis of carpal tunnel
      syndrome and a reliable method for its calculation.
AB  - INTRODUCTION: The aim of this study was to investigate factors affecting median
      nerve cross-sectional area (CSA) and determine a dependable swelling ratio (SR)
      calculation method. METHODS: Using ultrasonography, median nerve CSAs were
      measured at the tunnel inlet, midtunnel, and outlet, and at 4 cm and 12 cm
      proximal to the wrist. We used CSAmax as the largest of the tunnel measurements
      and calculated swelling ratios (SRs) by using the CSAmax. Sonographic
      measurements were correlated with electrophysiologic findings. We evaluated the
      effects of gender, weight, and height on median nerve thickness. RESULTS: We
      studied 95 wrists of 55 CTS patients and 48 wrists of 27 volunteers. Gender,
      weight, and height had effects on certain median nerve CSA measurements. CSAmax,
      SRmax4, and SRmax12 had superior correlations with electrophysiologic findings.
      The correlation between 4-cm and 12-cm median nerve CSAs was statistically
      significant (r = 0.879 and P < 0,001). CONCLUSION: We have developed a reliable
      SR method considering factors affecting median nerve CSA.

PMID- 23169556
TI  - Twentieth-century changes in the genetic composition of Swedish field pea
      metapopulations.
AB  - Landrace crops are formed by local adaptation, genetic drift and gene flow
      through seed exchange. In reverse, the study of genetic structure between
      landrace populations can reveal the effects of these forces over time. We present
      here the analysis of genetic diversity in 40 Swedish field pea (Pisum sativum L.)
      populations, either available as historical seed samples from the late nineteenth
      century or as extant gene bank accessions assembled in the late twentieth
      century. The historical material shows constant high levels of within-population
      diversity, whereas the extant accessions show varying, and overall lower, levels
      of within-population diversity. Structure and principal component analysis
      cluster most accessions, both extant and historical, in groups after geographical
      origin. County-wise analyses of the accessions show that the genetic diversity of
      the historical accessions is largely overlapping. In contrast, most extant
      accessions show signs of genetic drift. They harbor a subset of the alleles found
      in the historical accessions and are more differentiated from each other. These
      results reflect how, historically present metapopulations have been preserved
      during the twentieth century, although as genetically isolated populations.

PMID- 23169557
TI  - Absence of gene flow between diploids and hexaploids of Aster amellus at multiple
      spatial scales.
AB  - The potential for gene exchange across ploidy levels has long been recognized,
      but only a few studies have explored the rate of gene flow among different
      cytotypes. In addition, most of the existing knowledge comes from contact zones
      between diploids and tetraploids. The purpose of this paper was to investigate
      relationships between diploid and hexaploid individuals within the Aster amellus
      aggregate. A. amellus is known to occur in diploid and hexaploid cytotypes in
      Europe, with a complex contact zone in central Europe. Patterns of genetic
      diversity were investigated using seven microsatellite loci at three different
      spatial scales: (1) in the single known mixed-ploidy population; (2) in
      populations at the contact zone and (3) in a wider range of populations across
      Europe. The results show clear separation of the cytotypes at all three spatial
      scales. In addition, analysis of molecular variance strongly supported a model
      predicting a single origin of the hexaploids, with no or very limited gene flow
      between the cytotypes. Some hexaploid individuals found in the mixed-ploidy
      population, however, fell into the diploid cluster. This could suggest recurrent
      polyploid formation or occasional cross-pollination between cytotypes; however,
      there are strong post-zygotic breeding barriers between the two cytotypes, making
      the latter less plausible. Overall, the results suggest that the cytotypes could
      represent two cryptic species. Nevertheless, their formal separation is difficult
      as they cannot be distinguished morphologically, occupy very similar habitat
      conditions and have largely overlapping distribution ranges. These results show
      that polyploid complexes must be treated with caution as they can hide biological
      diversity and can have different adaptation potentials, evolving independently.

PMID- 23169558
TI  - Sex-determining chromosomes and sexual dimorphism: insights from genetic mapping
      of sex expression in a natural hybrid Fragaria * ananassa subsp. cuneifolia.
AB  - We studied the natural hybrid (Fragaria * ananassa subsp. cuneifolia) between two
      sexually dimorphic octoploid strawberry species (Fragaria virginiana and Fragaria
      chiloensis) to gain insight into the dynamics of sex chromosomes and the genesis
      of sexual dimorphism. Male sterility is dominant in both the parental species and
      thus will be inherited maternally, but the chromosome that houses the sex
      determining region differs. Thus, we asked whether (1) the cytotypic composition
      of hybrid populations represents one or both maternal species, (2) the sex
      determining chromosome of the hybrid reflects the location of male sterility
      within the maternal donor species and (3) crosses from the hybrid species show
      less sexual dimorphism than the parental species. We found that F. * ananassa
      subsp. cuneifolia populations consisted of both parental cytotypes but one
      predominated within each population. Genetic linkage mapping of two crosses
      showed dominance of male sterility similar to the parental species, however, the
      map location of male sterility reflected the maternal donor in one cross, but not
      the other. Moreover, female function mapped to a single region in the first
      cross, but to two regions in the second cross. Aside from components of female
      function (fruit set and seed set), other traits that have been found to be
      significantly sexually dimorphic in the pure species were either not dimorphic or
      were dimorphic in the opposite direction to the parental species. These results
      suggest that hybrids experience some disruption of dimorphism in secondary sexual
      traits, as well as novel location and number of quantitative trait locus (QTL)
      affecting sex function.

PMID- 23169559
TI  - Demographic factors shaped diversity in the two gene pools of wild common bean
      Phaseolus vulgaris L.
AB  - Wild common bean (Phaseolus vulgaris L.) is distributed throughout the Americas
      from Mexico to northern Argentina. Within this range, the species is divided into
      two gene pools (Andean and Middle American) along a latitudinal gradient. The
      diversity of 24 wild common bean genotypes from throughout the geographic range
      of the species was described by using sequence data from 13 loci. An isolation
      migration model was evaluated using a coalescent analysis to estimate multiple
      demographic parameters. Using a Bayesian approach, Andean and Middle American
      subpopulations with high percentage of parentages were observed. Over all loci,
      the Middle American gene pool was more diverse than the Andean gene pool
      (pi(sil)=0.0089 vs 0.0068). The two subpopulations were strongly genetically
      differentiated over all loci (F(st)=0.29). It is estimated that the two current
      wild gene pools diverged from a common ancestor ~111 000 years ago. Subsequently,
      each gene pool underwent a bottleneck immediately after divergence and lasted ~40
      000 years. The Middle American bottleneck population size was ~46% of the
      ancestral population size, whereas the Andean was 26%. Continuous asymmetric gene
      flow was detected between the two gene pools with a larger number of migrants
      entering Middle American gene pool from the Andean gene pool. These results
      suggest that because of the complex population structure associated with the
      ancestral divergence, subsequent bottlenecks in each gene pool, gene pool
      specific domestication and intense selection within each gene pool by breeders;
      association mapping would best be practised within each common bean gene pool.

PMID- 23169560
TI  - The maternal cytoplasmic environment may be involved in the viability selection
      of gametes and zygotes.
AB  - Segregation distortion is the phenomenon whereby the observed genotypic
      frequencies of a locus fall outside the expected Mendelian segregation ratio, and
      it is increasingly recognised as a potentially powerful evolutionary force. The
      main reason for segregation distortion is a difference in the viability of
      gametes and zygotes caused by viability loci in the segregating progeny. However,
      the maternal cytoplasm may also be involved in the viability selection of gametes
      and zygotes. The objectives of this study were to map the segregation distortion
      loci (SDL) in maize and to test the hypothesis that the viability of gametes and
      zygotes may also be associated with the maternal cytoplasmic environment. In the
      present study, a reciprocal mating design was conducted to generate an F2
      segregating population. A linkage map was constructed with 126 microsatellite
      markers. A whole-genome scan was performed to detect the SDL in segregating
      populations with different maternal cytoplasm environments. Altogether, 14 SDL
      with strong LOD (logarithm (base 10) of odds) supports were identified in the
      specifically designed F2 populations. Interestingly, we found dramatic changes in
      the genotypic frequencies of the SDL in the two maternal cytoplasmic backgrounds,
      which indicated a change in the viability of gametes and zygotes in different
      cytoplasmic environments. Furthermore, in the JB cytoplasmic background, most of
      the detected SDL and complete distortion markers exhibited similar bias patterns
      favouring the Y53 alleles. These results suggested that selfish cytoplasmic
      elements may have an important role in shaping the patterns of segregation
      distortion in F2 populations through selective viability of gametes and zygotes.

PMID- 23169561
TI  - The basis of antagonistic pleiotropy in hfq mutations that have opposite effects
      on fitness at slow and fast growth rates.
AB  - Mutations beneficial in one environment may cause costs in different
      environments, resulting in antagonistic pleiotropy. Here, we describe a novel
      form of antagonistic pleiotropy that operates even within the same environment,
      where benefits and deleterious effects exhibit themselves at different growth
      rates. The fitness of hfq mutations in Escherichia coli affecting the RNA
      chaperone involved in small-RNA regulation is remarkably sensitive to growth
      rate. E. coli populations evolving in chemostats under nutrient limitation
      acquired beneficial mutations in hfq during slow growth (0.1 h(-1)) but not in
      populations growing sixfold faster. Four identified hfq alleles from parallel
      populations were beneficial at 0.1 h(-1) and deleterious at 0.6 h(-1). The hfq
      mutations were beneficial, deleterious or neutral at an intermediate growth rate
      (0.5 h(-1)) and one changed from beneficial to deleterious within a 36 min
      difference in doubling time. The benefit of hfq mutations was due to the greater
      transport of limiting nutrient, which diminished at higher growth rates. The
      deleterious effects of hfq mutations at 0.6 h(-1) were less clear, with decreased
      viability a contributing factor. The results demonstrate distinct pleiotropy
      characteristics in the alleles of the same gene, probably because the altered
      residues in Hfq affected the regulation of expression of different genes in
      distinct ways. In addition, these results point to a source of variation in
      experimental measurement of the selective advantage of a mutation; estimates of
      fitness need to consider variation in growth rate impacting on the magnitude of
      the benefit of mutations and on their fitness distributions.

PMID- 23169562
TI  - Hybridisation and genetic diversity in introduced Mimulus (Phrymaceae).
AB  - Hybridisation among taxa with different ploidy levels is often associated with
      hybrid sterility. Clonal reproduction can stabilise these hybrids, but pervasive
      clonality may have a profound impact on the distribution of genetic diversity in
      natural populations. Here we investigate a widespread triploid taxon resulting
      from hybridisation between diploid Mimulus guttatus and tetraploid Mimulus
      luteus, two species that were introduced into the United Kingdom (UK) in the
      nineteenth century. This hybrid, Mimulus x robertsii, is largely sterile but
      capable of prolific vegetative propagation and has been recorded in the wild
      since 1872. We surveyed 40 Mimulus populations from localities across the UK to
      examine the current incidence of hybrids, and selected seventeen populations for
      genetic analysis using codominant markers. Cluster analyses revealed two main
      groups of genetically distinct individuals, corresponding to either diploid (M.
      guttatus) or polyploid (M. luteus and M. x robertsii) samples. Triploid hybrids
      were found in around 50% of sampled sites, sometimes coexisting with one of the
      parental species (M. guttatus). The other parent, M. luteus, was restricted to a
      single locality. Individual populations of M. x robertsii were genetically
      variable, containing multiple, highly heterozygous clones, with the majority of
      genetic variation distributed among- rather than within populations. Our findings
      demonstrate that this largely sterile, clonal taxon can preserve non-negligible
      amounts of genetic variation. The presence of genetically variable hybrid
      populations may provide the material for the continued success of asexual taxa in
      diverse environments.

PMID- 23169563
TI  - Unravelling gene expression of complex crop genomes.

PMID- 23169564
TI  - Inbreeding depression in urban environments of the bird's nest fungus Cyathus
      stercoreus (Nidulariaceae: Basidiomycota).
AB  - Many organisms display codispersal of offspring, but fewer display codispersal of
      compatible gametes. This mechanism enhances the ability of a species to colonize
      after long distance dispersal as a mechanism of reproductive assurance, but it
      also fosters inbreeding and potential reduction in fitness. Here we investigated
      both long distance dispersal and inbreeding in the bird's nest fungus Cyathus
      stercoreus, a dung and mulch-associated fungus with a splash cup fruiting body
      appearing like a miniature bird's nest of 'eggs' or peridioles that contain
      thousands of mating compatible meiotic spores. To investigate the genetic
      structure in the species, six North American urban populations were
      hierarchically sampled and genotyped using 10 microsatellite markers. We detected
      significant levels of inbreeding through heterozygote deficiencies at four loci,
      with global FIS=0.061. Dispersal limitation was suggested by both spatial
      autocorrelation and the detection of population structure between Louisiana and
      Michigan using clustering and F-statistics. Although inbreeding may facilitate
      colonization by the fungus, it has a negative effect on the fitness of
      populations as estimated from a 15% reduction in growth rates of inbred strains
      relative to outcrossed. Mating tests revealed that C. stercoreus has a higher
      estimated number of mating-type alleles (MAT-A= 39, MAT-B= 24) than other species
      of bird's nest fungi, which would increase its outcrossing efficiency. We
      speculate that the increased number of mating-type alleles is the result of a
      recent range and population size expansion into urban environments.

PMID- 23169565
TI  - Homoeolog expression bias and expression level dominance in allopolyploid cotton.
AB  - Allopolyploidy is an evolutionary and mechanistically intriguing process, in that
      it entails the reconciliation of two or more sets of diverged genomes and
      regulatory interactions. In this study, we explored gene expression patterns in
      interspecific hybrid F(1), and synthetic and natural allopolyploid cotton using
      RNA-Seq reads from leaf transcriptomes. We determined how the extent and
      direction of expression level dominance (total level of expression for both
      homoeologs) and homoeolog expression bias (relative contribution of homoeologs to
      the transcriptome) changed from hybridization through evolution at the polyploid
      level and following cotton domestication. Genome-wide expression level dominance
      was biased toward the A-genome in the diploid hybrid and natural allopolyploids,
      whereas the direction was reversed in the synthetic allopolyploid. This biased
      expression level dominance was mainly caused by up- or downregulation of the
      homoeolog from the 'non-dominant' parent. Extensive alterations in homoeolog
      expression bias and expression level dominance accompany the initial merger of
      two diverged diploid genomes, suggesting a combination of regulatory (cis or
      trans) and epigenetic interactions that may arise and propagate through the
      transcriptome network. The extent of homoeolog expression bias and expression
      level dominance increases over time, from genome merger through evolution at the
      polyploid level. Higher rates of transgressive and novel gene expression patterns
      as well as homoeolog silencing were observed in natural allopolyploids than in
      F(1) hybrid and synthetic allopolyploid cottons. These observations suggest that
      natural selection reconciles the regulatory mismatches caused by initial genomic
      merger, while new gene expression conditions are generated for evaluation by
      selection.

PMID- 23169567
TI  - Management of the unholy trinity diabetes-obesity-hypertension (diabesotension).
AB  - Diabetes, obesity and hypertension are common conditions and their concurrence is
      more common than would have been expected: 15% of the developed world suffer from
      the triad of "diabesotension". The pathophysiology involves characteristic
      neurohormonal profiles that collectively suggest the consideration of
      diabesotension as a distinct clinical entity. Diabesotensive patients have double
      the risk of suffering from the micro and macrovascular complications of each of
      the conditions alone. Therefore, it is critical to reduce their overall risk and
      provide them with special attention. Studies have shown that the number needed to
      treat in diabesotension is lower compared to non-obese. Appropriate treatment
      goals should be set. With regards to hypertension, recent clinical trials point
      to 130-135/80-85 mmHg. Lifestyle modifications are critical, therefore DASH and
      Mediterranean diet should be recommended along with a physical training program.
      Weight reduction strategies often fail and bariatric surgery should be
      considered. All antihypertensive drug-classes are adequate to treat uncomplicated
      diabesotension and it is not mandatory to include RAAS blockers as first-line
      therapy. However, as second line, for high risk patients and patients with
      nephropathy - a RAAS blocker is indicated. Combination therapy is almost always
      prescribed in the course of the disease. In the absence of compelling
      indications, a RAAS blocker with a calcium-channels blocker is preferred as it
      provides benefits beyond blood pressure control. Resistant hypertension is
      common, and secondary causes should be looked for, particularly sleep apnea. A
      novel procedure such as renal denervation is a promising option due to its
      antihypertensive and metabolic benefits. Copyright (c) 2012 John Wiley & Sons,
      Ltd.

PMID- 23169566
TI  - Tongue muscle plasticity following hypoglossal nerve stimulation in aged rats.
AB  - INTRODUCTION: Age-related decreases in tongue muscle mass and strength have been
      reported. It may be possible to prevent age-related tongue muscle changes using
      neuromuscular electrical stimulation (NMES). Our hypothesis was that alterations
      in muscle contractile properties and myosin heavy chain composition would be
      found after NMES. METHODS: Fifty-four young, middle-aged, and old 344/Brown
      Norway rats were included in this study. Twenty-four rats underwent bilateral
      electrical stimulation of the hypoglossal nerves for 8 weeks and were compared
      with control or sham rats. Muscle contractile properties and myosin heavy chain
      (MHC) in the genioglossus (GG), styloglossus (SG), and hyoglossus (HG) muscles
      were examined. RESULTS: Compared with unstimulated control rats, we found reduced
      muscle fatigue, increased contraction and half-decay times, and increased twitch
      and tetanic tension. Increased type I MHC was found, except for in GG in old and
      middle-aged rats. CONCLUSION: Transitions in tongue muscle contractile properties
      and phenotype were found after NMES.

PMID- 23169568
TI  - 7,7,8,8-Tetraaryl-o-quinodimethane stabilized by dibenzo annulation: a helical pi
      electron system that exhibits electrochromic and unique chiroptical properties.
AB  - When two benzene rings are fused to a tetraaryl-o-quinodimethane skeleton,
      sterically hindered helical molecules 1 acquire a high thermodynamic stability.
      Because the tetraarylbutadiene subunit contains electron-donating alkoxy groups,
      1 undergo reversible two-electron oxidation to 2(2+), which can be isolated as
      deeply colored stable salts. Intramolecular transfer of the point chirality
      (e.g., sec-butyl) on the aryl groups to helicity induces a diastereomeric
      preference in dications 2 b(2+) and 2 c(2+), which represents an efficient method
      for enhancing circular-dichroism signals. Thus, those redox pairs can serve as
      new electrochiroptical response systems. X-ray analysis of dication 2(2+)
      revealed pi-pi stacking interaction of the diarylmethylium moieties, which is
      also present in solution. The stacking geometry is the key contributor to the
      chirosolvatochromic response.

PMID- 23169569
TI  - Nasal backflow and the difficulty of relaxation in the upper esophageal
      sphincter.
AB  - OBJECTIVES/HYPOTHESIS: Nasal backflow is the regurgitation of material into
      nasopharynx during swallowing and it can be easily observed by videofluoroscopy.
      We aimed to evaluate the association between nasal backflow and the prevalence of
      aspiration, as well as the relationship between nasal backflow and the opening of
      the upper esophageal sphincter. STUDY DESIGN: Retrospective case-control study.
      METHODS: There were 182 cases of videofluoroscopic swallowing studies that were
      retrospectively reviewed. The presence of nasal backflow and laryngeal
      aspirations were checked, and the anteroposterior maximum width of the upper
      esophageal sphincter opening was measured on lateral images of videofluoroscopic
      swallowing studies. The difference in maximum upper esophageal sphincter width
      between the group with nasal backflow and the group without nasal backflow was
      statistically verified. RESULTS: Twenty patients showed nasal backflow, which was
      closely related to laryngeal aspiration (odds ratio = 10.97; 95% CI = 2.46-48.85;
      P < 0.05). Their maximal upper esophageal sphincter width (mean +/- standard
      deviation) was 6.82 +/- 1.96 mm and significantly different from the group
      without nasal backflow (9.35 +/- 1.56 mm) (P < 0.05). CONCLUSION: Nasal backflow
      was closely associated with the presence of aspiration; the opening of upper
      esophageal sphincters significantly decreased in the cases of nasal backflow.

PMID- 23169570
TI  - Anatomy and physiology of the clitoris, vestibular bulbs, and labia minora with a
      review of the female orgasm and the prevention of female sexual dysfunction.
AB  - This review, with 21 figures and 1 video, aims to clarify some important aspects
      of the anatomy and physiology of the female erectile organs (triggers of orgasm),
      which are important for the prevention of female sexual dysfunction. The clitoris
      is the homologue of the male's glans and corpora cavernosa, and erection is
      reached in three phases: latent, turgid, and rigid. The vestibular bulbs cause
      "vaginal" orgasmic contractions, through the rhythmic contraction of the
      bulbocavernosus muscles. Because of the engorgement with blood during sexual
      arousal, the labia minora become turgid, doubling or tripling in thickness. The
      corpus spongiosum of the female urethra becomes congested during sexual arousal;
      therefore, male erection equals erection of the female erectile organs. The
      correct anatomical term to describe the erectile tissues responsible for female
      orgasm is the female penis. Vaginal orgasm and the G-spot do not exist. These
      claims are found in numerous articles that have been written by Addiego F,
      Whipple B, Jannini E, Buisson O, O'Connell H, Brody S, Ostrzenski A, and others,
      have no scientific basis. Orgasm is an intense sensation of pleasure achieved by
      stimulation of erogenous zones. Women do not have a refractory period after each
      orgasm and can, therefore, experience multiple orgasms. Clitoral sexual response
      and the female orgasm are not affected by aging. Sexologists should define having
      sex/love making when orgasm occurs for both partners with or without vaginal
      intercourse.

PMID- 23169571
TI  - miRNAs as modulators of angiogenesis.
AB  - MicroRNAs are highly expressed in endothelial cells, and recent data suggest that
      they regulate aspects of vascular development and angiogenesis. This study
      highlights the state of the art in this field and potential therapeutic
      opportunities. MicroRNAs (miRNAs) represent a family of conserved short (~22 nt)
      noncoding single-stranded RNAs that have been identified in plants and animals.
      They are generated by the sequential processing of the RNA template by the
      enzymes Drosha and Dicer, and mature miRNAs can regulate the levels of gene
      expression at the posttranscriptional level. miRNAs participate in a diverse
      range of regulatory events via regulation of genes involved in the control of
      processes such as development, differentiation, homeostasis, metabolism, growth,
      proliferation, and apoptosis. However, rather than functioning as regulatory on
      off switches, miRNAs often function to modulate or fine-tune cellular phenotypes.
      So far, more than 1000 mammalian miRNAs have been identified since the discovery
      of the first two miRNAs (lin-4 and let-7), and bioinformatics predictions
      indicate that mammalian miRNAs can regulate ~30% of all protein-coding genes.

PMID- 23169574
TI  - Ethanol decomposition on a Pd(110) surface: a density functional theory
      investigation.
AB  - Ethanol decomposition on Pd(110) is comprehensively investigated using self
      consistent periodic density functional theory. Geometries and energies for all
      the intermediates involved are analyzed, and the decomposition network is mapped
      out to illustrate the reaction mechanism. On Pd(110), the most stable adsorption
      of the involved species tends to follow the gas-phase bond order rules, wherein C
      is tetravalent and O is divalent with the missing H atoms replaced by metal
      atoms. The most likely decomposition pathway of ethanol on Pd(110) is
      CH(3)CH(2)OH -> CH(3)CH(2)O -> CH(3)CHO -> CH(3)CO -> CH(3) + CO -> CO + H +
      CH(4) + C, in which the initial dehydrogenation is the rate-limited step. No C-O
      scission pathway is identified. Comparing with ethanol decomposition on Pd(111)
      [Langmuir, 2010, 26, 1879-1888], Pd(110) characterizes relatively high activity
      and different selectivity. Two crucial factors controlling the variations of
      reactivity and selectivity from Pd(111) to Pd(110), i.e., the local electronic
      effect of the metals and the geometrical effect of the relevant transition
      states, are identified. Four distinct Bronsted-Evans-Polanyi (BEP) relations are
      identified for the three types of bond scission (C-H, C-O, and C-C) if we
      consider Pd(111) and Pd(110) as a whole, one for C-H bond scission, one for C-O
      bond scission, and two for C-C bond scission.

PMID- 23169573
TI  - Evaluation of genetic counseling among cystic fibrosis carriers, Michigan Newborn
      Screening.
AB  - OBJECTIVE: A quality improvement (QI) strategy to improve the rate of genetic
      counseling (GC) services was initiated in cystic fibrosis (CF) care Center E in
      2010. This statewide study was conducted to determine: (1) GC rates before and
      after implementation of the QI strategy at Center E; (2) characteristics
      associated with not receiving GC; and (3) topic areas addressed during GC.
      METHODS: The retrospective study included 1,097 CF carriers born from 2008 to
      2011 identified through Michigan's Newborn Screening Program. Rate of GC services
      was determined for Center E and the other four CF centers before and after the QI
      change. Bivariate and multivariable logistic regression was used to determine
      associations between select characteristics and not receiving GC. Topic areas
      discussed during GC sessions were assessed using frequency tables. RESULTS: Rate
      of GC services in Center E increased from 23% in 2008-2010 to 91% in 2011, while
      at the other centers approximately 92% received GC services across those years.
      In 2008-2010, being seen at Center E and black race were significantly associated
      with increased likelihood of not receiving GC services in adjusted analyses. In
      2011, neither characteristic was associated with receipt of GC. Of 16 target
      topic areas, all were discussed in 85% of GC sessions. CONCLUSIONS: Implementing
      a QI strategy of providing sweat test results at the GC appointment within Center
      E resulted in more CF carriers receiving comprehensive GC services. Center
      specific procedure differences should be assessed to increase rate of GC services
      following a positive CF newborn screen.

PMID- 23169575
TI  - Model and mechanism: N-hydroxylation of primary aromatic amines by cytochrome
      P450.
AB  - Only one path applies: to date, five different mechanisms have been suggested for
      the P450-catalyzed N-hydroxylation of primary aromatic amines. Computational
      analysis employing density functional theory demonstrates that only the H-atom
      transfer pathway, that is H abstraction from an amine N followed by a radical
      rebound step, on a low-spin route can contribute to the aromatic hydroxylamine
      formation.

PMID- 23169576
TI  - ApoA-1 mimetic restores adiponectin expression and insulin sensitivity
      independent of changes in body weight in female obese mice.
AB  - BACKGROUND: We examined the ability of the apolipoprotein AI mimetic peptide L-4F
      to improve the metabolic state of female and male ob mice and the mechanisms
      involved. METHODS: Female and male lean and obese (ob) mice were administered L
      4F or vehicle for 6 weeks. Body weight was measured weekly. Fat distribution,
      serum cytokines and markers of cardiovascular dysfunction were determined at the
      end of treatment. RESULTS: L-4F significantly decreased serum interleukin (IL)-6,
      tumor necrosis factor-alpha and IL-1beta. L-4F improved vascular function, and
      increased serum adiponectin levels and insulin sensitivity compared with
      untreated mice. In addition, L-4F treatment increased heme oxygenase (HO)-1, pAKT
      and pAMPK levels in kidneys of ob animals. pAKT and pAMPK levels were
      significantly reduced in the presence of an HO inhibitor. Interestingly, L4F did
      not alter body weight in female mice, but caused a significant reduction in
      males. CONCLUSIONS: L-4F treatments reduced cardiovascular risk factors and
      improved insulin sensitivity in female ob mice independent of body fat changes.
      Reduced inflammatory cytokine levels accompanied by increased HO activity, serum
      adiponectin and improved insulin sensitivity suggest that L-4F may promote the
      conversion of visceral fat to a healthier phenotype. Therefore, L-4F appears to
      be a promising therapeutic strategy for treating both cardiovascular risk factors
      and insulin resistance in obese patients of either gender.

PMID- 23169577
TI  - Factors associated with night-time calf muscle cramps: a case-control study.
AB  - INTRODUCTION: Although highly prevalent and painful, night-time calf muscle
      cramping is poorly understood, and no treatment has shown consistent efficacy or
      safety. METHODS: One hundred sixty adults were recruited from New South Wales,
      Australia, including 80 who had night-time calf cramping at least once per week
      and 80 age- and gender-matched adults who did not. Participants were assessed
      using reliable tests of lower limb strength, flexibility, morphometrics,
      circulation, and sensation, and were questioned about health and lifestyle
      factors, diet, medications, exercise, symptomatology, sleeping habits, and
      footwear. RESULTS: Conditional logistic regression identified 3 factors
      independently associated with night-time calf muscle cramps: muscle twitching (OR
      4.6, 95% CI 1.6-15.5, P = 0.01); lower limb tingling (OR 4.1, 95% CI 1.6-10.3, P
      = 0.003); and foot dorsiflexion weakness (OR 1.02, 95% CI 1.01-1.03, P = 0.002),
      which represented other measures of lower limb weakness in the model.
      CONCLUSIONS: Night-time calf muscle cramps were associated with markers of
      neurological dysfunction and potential musculoskeletal therapeutic targets.

PMID- 23169578
TI  - The UBIAD1 prenyltransferase links menaquinone-4 [corrected] synthesis to
      cholesterol metabolic enzymes.
AB  - Schnyder corneal dystrophy (SCD) is an autosomal dominant disease characterized
      by germline variants in UBIAD1 introducing missense alterations leading to
      deposition of cholesterol in the cornea, progressive opacification, and loss of
      visual acuity. UBIAD1 was recently shown to synthesize menaquinone-4 (MK-4,
      vitamin K(2) ), but causal mechanisms of SCD are unknown. We report a novel
      c.864G>A UBIAD1 mutation altering glycine 177 to glutamic acid (p.G177E) in six
      SCD families, including four families from Finland who share a likely founder
      mutation. We observed reduced MK-4 synthesis by UBIAD1 altered by SCD mutations
      p.N102S, p.G177R/E, and p.D112N, and molecular models showed p.G177-mutant UBIAD1
      disrupted transmembrane helices and active site residues. We show UBIAD1
      interacts with HMGCR and SOAT1, enzymes catalyzing cholesterol synthesis and
      storage, respectively, using yeast two-hybrid screening and immunoprecipitation.
      Docking simulations indicate cholesterol binds to UBIAD1 in the substrate-binding
      cleft and substrate-binding overlaps with GGPP binding, an MK-4 substrate,
      suggesting potential competition between these metabolites. Impaired MK-4
      synthesis is a biochemical defect identified in SCD suggesting UBIAD1 links
      vitamin K and cholesterol metabolism through physical contact between enzymes and
      metabolites. Our data suggest a role for endogenous MK-4 in maintaining cornea
      health and visual acuity.

PMID- 23169580
TI  - Utility, charge, and cost of inpatient and emergency department serum folate
      testing.
AB  - BACKGROUND: Serum folate levels are commonly ordered for multiple indications in
      the inpatient and emergency department settings. Since mandatory folic acid
      fortification in 1998, there has been a decreasing prevalence of folate
      deficiency in the United States. OBJECTIVE: Our objective was to determine the
      indications, rate of deficiency, charge and cost per deficient result, and change
      in management per deficient result in serum folate testing in inpatients and
      emergency department patients. DESIGN: Retrospective analysis of all inpatient
      and emergency department serum folate tests. METHODS: We analyzed all inpatient
      and emergency department serum folate tests performed over a 12-month period. We
      reviewed the charts of 250 patients and all low-normal or deficient serum folate
      levels to determine indications, comorbidities, and change in management based on
      result. Charge and cost analyses were performed. SETTING/PATIENTS: All inpatient
      and emergency department patients with a serum folate test performed at a major
      medical center in Boston, Massachusetts. RESULTS: A total of 2093 serum folate
      tests were performed in 1944 patients with 2 deficient levels. The most common
      indications were anemia without macrocytosis and anemia with macrocytosis. The
      amount charged per deficient result was $158,022. The cost to the hospital per
      deficient result was less than $2093. CONCLUSIONS: In folic acid fortified
      countries, serum folate testing has low utility and poor cost effectiveness for
      all indications in inpatients and emergency department patients.

PMID- 23169582
TI  - Novel FHL1 mutation in a family with reducing body myopathy.
AB  - INTRODUCTION: Reducing body myopathy is a rare X-linked myopathy. It is
      characterized by intracytoplasmic inclusions that stain with menadione-nitroblue
      tetrazolium. It is caused by mutations in the FHL1 gene, which encodes the four
      and-a-half LIM domain 1 protein (FHL1). METHODS: We performed a clinical, muscle
      MRI, and histopathological characterization and immunoblot and genetic analysis
      of the FHL1 protein in a family with 4 individuals affected by reducing body
      myopathy. RESULTS: We identified a novel missense mutation in FHL1 (c.449G>C;
      p.C150S). The patients presented with asymmetric proximal weakness and scoliosis.
      Both of the boys had a more severe course with earlier onset, contractures, and
      death due to heart failure at 14 and 18 years of age, respectively. MRI revealed
      fatty infiltration of posteromedial thigh and paraspinal muscles.
      Histopathological findings showed FHL1-immunoreactive inclusions. Immunoblot
      analysis revealed a 50% reduction of FHL1 protein. CONCLUSION: In this study we
      highlighted diagnostic clues in this myopathy and compared our data with the
      literature.

PMID- 23169579
TI  - Transcription elongation factor Tcea3 regulates the pluripotent differentiation
      potential of mouse embryonic stem cells via the Lefty1-Nodal-Smad2 pathway.
AB  - Self-renewal and pluripotency are hallmark properties of pluripotent stem cells,
      including embryonic stem cells (ESCs) and iPS cells. Previous studies revealed
      the ESC-specific core transcription circuitry and showed that these core factors
      (e.g., Oct3/4, Sox2, and Nanog) regulate not only self-renewal but also
      pluripotent differentiation. However, it remains elusive how these two cell
      states are regulated and balanced during in vitro replication and
      differentiation. Here, we report that the transcription elongation factor Tcea3
      is highly enriched in mouse ESCs (mESCs) and plays important roles in regulating
      the differentiation. Strikingly, altering Tcea3 expression in mESCs did not
      affect self-renewal under nondifferentiating condition; however, upon exposure to
      differentiating cues, its overexpression impaired in vitro differentiation
      capacity, and its knockdown biased differentiation toward mesodermal and
      endodermal fates. Furthermore, we identified Lefty1 as a downstream target of
      Tcea3 and showed that the Tcea3-Lefty1-Nodal-Smad2 pathway is an innate program
      critically regulating cell fate choices between self-replication and
      differentiation commitment. Together, we propose that Tcea3 critically regulates
      pluripotent differentiation of mESCs as a molecular rheostat of Nodal-Smad2/3
      signaling.

PMID- 23169583
TI  - Effects of tensor tympani muscle contraction on the middle ear and markers of a
      contracted muscle.
AB  - OBJECTIVES/HYPOTHESIS: Many otologic disorders have been attributed to
      dysfunction of the tensor tympani muscle, including tinnitus, otalgia, Meniere's
      disease and sensorineural hearing loss. The objective of this study was to
      determine adequate stimuli for tensor tympani contraction in humans and determine
      markers of the hypercontracted state that could be used to detect this process in
      otologic disease. STUDY DESIGN: Multiple types of studies. METHODS: Studies
      included 1) measuring middle ear impedance changes in response to orbital puffs
      of air, facial stroking, and self-vocalization; 2) measuring changes in stapes
      and eardrum vibrations and middle ear acoustic impedance in response to force
      loading of the tensor tympani in fresh human cadaveric temporal bones; 3)
      measuring changes in acoustic impedance in two subjects who could voluntarily
      contract their tensor tympani, and performing an audiogram with the muscle
      contracted in one of these subjects; and 4) developing a lumped parameter
      computer model of the middle ear while simulating various levels of tensor
      tympani contraction. RESULTS: Orbital jets of air are the most effective stimuli
      for eliciting tensor tympani contraction. As markers for tensor tympani
      contraction, all investigations indicate that tensor tympani hypercontraction
      should result in a low-frequency hearing loss, predominantly conductive, with a
      decrease in middle ear compliance. CONCLUSIONS: These markers should be searched
      for in otologic pathology states where the tensor tympani is suspected of being
      hypercontracted.

PMID- 23169584
TI  - Epidemiology and clinical manifestations of children with macrolide-resistant
      Mycoplasma pneumoniae pneumonia in Taiwan.
AB  - Mycoplasma pneumoniae accounts for 10-30% of community-acquired pneumonia (CAP)
      in children. This study reveals the epidemiology and clinical manifestations of
      children with macrolide-resistant (ML(r) ) M. pneumoniae pneumonia in Taiwan.
      Respiratory tract specimens were collected from children hospitalized with CAP
      for evaluation via PCR followed by DNA sequencing for several point mutations
      related to the ML(r) character. Of the 412 specimens collected during the study
      period, 60 (15%) were positive for M. pneumoniae, 14 (23%) of which presented
      point mutation (all A2063G) in 23S rRNA. Clinical symptoms and chest X-ray
      findings between the ML(s) and ML(r) groups were not significantly different.
      However, the ML(r) group had longer mean duration of fever after azithromycin
      treatment (3.2 days vs. 1.6 days, P = 0.02) and significantly higher percentage
      of changing antibiotics for suspected ML(r) strain (42% vs. 13%, P = 0.04).
      Although 58% of children in the ML(r) group did not receive effective
      antibiotics, all children were discharged without sequelae. In conclusion, 15% of
      CAP in children is caused by M. pneumoniae and the macrolide-resistance rate is
      23% in Taiwan. Despite ineffective antibiotics, children with ML(r) M. pneumoniae
      pneumonia recover completely.

PMID- 23169585
TI  - The influence of protein folding on the copper affinities of trafficking and
      target sites.
AB  - The relative influence of protein unfolding on the Cu(I) affinity of trafficking
      and target sites for copper has been determined. For the copper metallochaperone
      Atx1 from Synechocystis PCC 6803 (a cyanobacterium), Saccharomyces cerevisiae and
      humans unfolding in urea results in a decrease in the Cu(I) affinity from (4-5) *
      10(17) M(-1) to (1-3) * 10(16) M(-1) at pH 7. The affinities of the unfolded
      Atx1s are similar to those for CXXC-containing peptides. Partial unfolding, due
      to the loop 5 His61Lys mutation in Synechocystis Atx1, gives rise to a more
      limited decrease in Cu(I) affinity. For the copper target protein plastocyanin
      from Synechocystis, chemical unfolding results in the Cu(I) affinity decreasing
      by 5-orders of magnitude. This differential influence of protein unfolding on
      Cu(I) affinity is due to a more complex copper site structure in the target
      protein, including numerous interactions of non-coordinating residues with
      ligating amino acids. This second-coordination sphere is much simpler in the
      Atx1s with the main interaction provided by the loop 5 residue that tunes the
      Cu(I) affinity by altering the pK(a) of the C-terminal Cys ligand of the CXXC
      motif. This interaction and others are absent in the unfolded Atx1s and the two
      Cys ligands have pK(a) values reminiscent of free thiols (>8) resulting in
      lowered Cu(I) affinities at pH 7. Residues close to the active site of the thiol
      disulfide oxidoreductase thioredoxin appear to lower the Cu(I) affinity of its
      CXXC motif to 3.1 * 10(15) M(-1) at pH 7, presumably to prevent copper binding in
      vivo. The structure of a copper site, including the number and relative position
      of ligands in the primary structure and the complexity of the second-coordination
      sphere, results in dramatically different effects of unfolding on Cu(I) affinity
      that has important implications for copper homeostasis.

PMID- 23169586
TI  - Association of coffee consumption with serum adiponectin, leptin, inflammation
      and metabolic markers in Japanese workers: a cross-sectional study.
AB  - BACKGROUND: Mechanisms underlying coffee's beneficial actions against
      cardiovascular disease and glucose metabolism are not well understood. Little
      information is available regarding association between coffee consumption and
      adipocytokines. OBJECTIVE: We investigated potential associations between coffee
      consumption and adiponectin, leptin, markers for subclinical inflammation,
      glucose metabolism, lipids and liver enzymes. We then investigated whether
      adipocytokines played a role in the association between coffee consumption and
      these markers. DESIGN AND SUBJECTS: This is a cross-sectional study comprising
      2554 male and 763 female Japanese workers. Potential relations between coffee
      consumption and adipocytokines or other markers were evaluated using a multiple
      linear regression model adjusted for confounding factors. We evaluated whether
      adiponectin and leptin partly explain the associations between coffee consumption
      and each marker by multiple mediation analysis. RESULTS: Coffee consumption
      showed significant positive associations with adiponectin and total and low
      density lipoprotein cholesterol, and inverse associations with leptin, high
      sensitivity C-reactive protein (hs-CRP), triglycerides and liver enzymes (all
      P<0.05). An adjustment for adiponectin and leptin significantly attenuated the
      associations between coffee consumption and hs-CRP or triglycerides, but not for
      liver enzymes. No associations were observed between coffee consumption and
      glucose metabolism-related markers. CONCLUSION: Coffee consumption was associated
      with high adiponectin and low leptin levels. We speculated that adipocytokines
      mainly explain the associations of coffee consumption with lipids and hs-CRP.
      Factors other than adipocytokines may explain the association between coffee
      consumption and liver function.

PMID- 23169587
TI  - Atlantic salmon type I IFN subtypes show differences in antiviral activity and
      cell-dependent expression: evidence for high IFNb/IFNc-producing cells in fish
      lymphoid tissues.
AB  - This work reveals distinct roles of the two-cysteine-containing type I IFNs, IFNa
      and IFNd, and the four-cysteine-containing IFNb and IFNc in antiviral immunity of
      Atlantic salmon. IFNa and IFNc showed similar antiviral activities and ability to
      induce antiviral genes, IFNb was less active, and IFNd showed no activity.
      Expression of IFNs was compared by treatment of cells or fish with the dsRNA
      polyinosinic-polycytidylic acid [poly(I:C)], which induces IFNs via the viral RNA
      receptors MDA5 and TLR3/TLR22 and with the imidazoquinoline R848, which induces
      IFNs via TLR7. Poly(I:C) strongly induced IFNa in cell lines, whereas the other
      IFNs showed little response, indicating that IFNa is the main IFN subtype induced
      through the RIG-I/MDA5 pathway. In contrast, IFNb and IFNc are the main IFNs
      induced through the TLR7 pathway because R848 induced high transcript levels of
      IFNb and IFNc and low transcript levels of IFNa in the head kidney and spleen.
      IFNd was constitutively expressed in cells and organs but showed no response to
      poly(I:C) or R848. Fluorescence in situ hybridization studies showed that
      poly(I:C) induced IFNa and IFNc in a variety of cells in the head kidney, spleen,
      gills, liver, and heart, whereas R848 induced coexpression of IFNb and IFNc in
      distinct cells in head kidney and spleen. These cells are likely to be
      specialized high IFN producers because they were few in numbers despite high
      IFNb/IFNc transcript levels in the same organs. High IFN expression in response
      to TLR7 ligation is a feature shared by mammalian plasmacytoid dendritic cells.

PMID- 23169588
TI  - Cutting edge: IL-13Ralpha1 expression in dopaminergic neurons contributes to
      their oxidative stress-mediated loss following chronic peripheral treatment with
      lipopolysaccharide.
AB  - Inflammation and its mediators, including cytokines and reactive oxygen species,
      are thought to contribute to neurodegeneration. In the mouse brain, we found that
      IL-13Ralpha1 was expressed in the dopaminergic (DA) neurons of the substantia
      nigra pars compacta, which are preferentially lost in human Parkinson's disease.
      Mice deficient for Il13ra1 exhibited resistance to loss of DA neurons in a model
      of chronic peripheral inflammation using bacterial LPS. IL-13, as well as IL-4,
      potentiated the cytotoxic effects of t-butyl hydroperoxide and hydrogen peroxide
      on mouse DA MN9D cells. Collectively, our data indicate that expression of IL
      13Ralpha1 on DA neurons can increase their susceptibility to oxidative stress
      mediated damage, thereby contributing to their preferential loss. In humans,
      Il13ra1 lies on the X chromosome within the PARK12 locus of susceptibility to
      Parkinson's disease, suggesting that IL-13Ralpha1 may have a role in the
      pathogenesis of this neurodegenerative disease.

PMID- 23169589
TI  - Bioinformatic and empirical analysis of novel hypoxia-inducible targets of the
      human antituberculosis T cell response.
AB  - We analyzed whole genome-based transcriptional profiles of Mycobacterium
      tuberculosis subjected to prolonged hypoxia to guide the discovery of novel
      potential Ags, by a combined bioinformatic and empirical approach. We analyzed
      the fold induction of the 100 most highly induced genes at 7 d of hypoxia, as
      well as transcript abundance, peptide-binding prediction (ProPred) adjusted for
      population-specific MHC class II allele frequency, and by literature search.
      Twenty-six candidate genes were selected by this bioinformatic approach and
      evaluated empirically using IFN-gamma and IL-2 ELISPOT using immunodominant Ags
      (Acr-1, CFP-10, ESAT-6) as references. Twenty-three of twenty-six proteins
      induced an IFN-gamma response in PBMCs of persons with active or latent
      tuberculosis. Five novel immunodominant proteins-Rv1957, Rv1954c, Rv1955,
      Rv2022c, and Rv1471-were identified that induced responses similar to CFP-10 and
      ESAT-6 in both magnitude and frequency. IL-2 responses were of lower magnitude
      than were those of IFN-gamma. Only moderate evidence of infection stage-specific
      recognition of Ags was observed. Reconciliation of bioinformatic and empirical
      hierarchies of immunodominance revealed that Ags could be predicted, providing
      transcriptomic data were combined with peptide-binding prediction adjusted by
      population-specific MHC class II allele frequency.

PMID- 23169591
TI  - Low-valent Ge(2) and Ge(4) species trapped by N-heterocyclic gallylene.
AB  - Much pi and no sigma: quantum chemical calculations showed that the Ge atoms of
      the Ga(2)Ge(2) core in Ge(2)[Ga(DPP)](2) are not bonded by sigma interactions,
      but rather by a transannular pi interaction. The compound is formed by reduction
      of (PCy(3))?GeCl(2) with Ga(DDP)/KC(8) which also yielded a further product
      Ge(4)[Ga(DPP)](2) with a Ge(4) tetrahedron (DDP=HC(CMeNC(6)H(3)-2,6-iPr(2))(2)).

PMID- 23169592
TI  - Validation of the modified LDIFlare technique: a simple and quick method to
      assess C-fiber function.
AB  - INTRODUCTION: In this study we validated a modified laser Doppler imager method
      (mLDIf) for assessing C-fiber function and compared it to the original (oLDIf).
      Both measure flare size in foot skin after heating, but the mLDIf uses 47 degrees
      C (vs. 44 degrees C), making it quicker and better suited for clinical use.
      METHODS: To confirm that mLDIf assesses C-fiber function, 5 healthy controls (HC)
      were studied before and after local anesthesia (LA). Reproducibility and
      comparison with oLDIf was assessed in HC (n = 16). Finally, diabetes subjects
      with (DN(+), n = 10) and without (DN(-), n = 16) neuropathy were studied.
      RESULTS: LA almost abolished the flare (9.3 +/- 3.0 cm(2) vs. 1.7 +/- 0.3 cm(2),
      P < 0.0001). mLDIf produced larger flares (9.9 +/- 3.4 vs. 5.7 +/- 2.3 cm(2), P <
      0.0001), but correlated with oLDIf (r = 0.81, P < 0.001). mLDIf was reduced in
      DN(-) (6.8 +/- 2.8 vs. HC, P = 0.003), markedly so in DN(+) (2.0 +/- 1.1 vs. HC
      and DN(-), P < 0.0001). CONCLUSION: The mLDIf is a quick, practical method for
      assessing C-fiber function in the clinical setting.

PMID- 23169590
TI  - miR-451 regulates dendritic cell cytokine responses to influenza infection.
AB  - MicroRNAs (miRNAs) are important posttranscriptional regulators in immune cells,
      but how viral infection regulates miRNA expression to shape dendritic cell (DC)
      responses has not been well characterized. We identified 20 miRNAs that were
      differentially expressed in primary murine DCs in response to the dsRNA agonist
      polyinosinic-polycytidylic acid, a subset of which were modestly regulated by
      influenza infection. miR-451 was unique because it was induced more strongly in
      primary splenic and lung DCs by live viral infection than by purified agonists of
      pattern recognition receptors. We determined that miR-451 regulates a subset of
      proinflammatory cytokine responses. Three types of primary DCs treated with
      antisense RNA antagomirs directed against miR-451 secreted elevated levels of IL
      6, TNF, CCL5/RANTES, and CCL3/MIP1alpha, and these results were confirmed using
      miR-451(null) cells. miR-451 negatively regulates YWHAZ/14-3-3zeta protein levels
      in various cell types, and we measured a similar inhibition of YWHAZ levels in
      DCs. It is known that YWHAZ can control the activity of two negative regulators
      of cytokine production: FOXO3, which is an inhibitory transcription factor, and
      ZFP36/Tristetraprolin, which binds to AU-rich elements within 3'-untranslated
      regions to destabilize cytokine mRNAs. Inhibition of miR-451 expression
      correlated with increased YWHAZ protein expression and decreased ZFP36
      expression, providing a possible mechanism for the elevated secretion of IL-6,
      TNF, CCL5/RANTES, and CCL3/MIP1alpha. miR-451 levels are themselves increased by
      IL-6 and type I IFN, potentially forming a regulatory loop. These data suggest
      that viral infection specifically induces a miRNA that directs a negative
      regulatory cascade to tune DC cytokine production.

PMID- 23169594
TI  - Person-job fit: an exploratory cross-sectional analysis of hospitalists.
AB  - BACKGROUND: Person-job fit is an organizational construct shown to impact the
      entry, performance, and retention of workers. Even as a growing number of
      physicians work under employed situations, little is known about how physicians
      select, develop, and perform in organizational settings. OBJECTIVE: Our objective
      was to validate in the hospitalist physician workforce features of person-job fit
      observed in workers of other industries. DESIGN: The design was a secondary
      survey data analysis from a national stratified sample of practicing US
      hospitalists. MEASURES: The measures were person-job fit; likelihood of leaving
      practice or reducing workload; organizational climate; relationships with
      colleagues, staff, and patients; participation in suboptimal patient care
      activities. RESULTS: Responses to the Hospital Medicine Physician Worklife Survey
      by 816 (sample response rate 26%) practicing hospitalists were analyzed. Job
      attrition and reselection improved job fit among hospitalists entering the job
      market. Better job fit was achieved through hospitalists engaging a variety of
      personal skills and abilities in their jobs. Job fit increased with time together
      with socialization and internalization of organizational values. Hospitalists
      with higher job fit felt they performed better in their jobs. CONCLUSIONS:
      Features of person-job fit for hospitalists conformed to what have been observed
      in nonphysician workforces. Person-job fit may be a useful complementary survey
      measure related to job satisfaction but with a greater focus on function.

PMID- 23169593
TI  - Prostaglandin E2 increases hematopoietic stem cell survival and accelerates
      hematopoietic recovery after radiation injury.
AB  - Hematopoietic stem and progenitor cells (HSPCs), which continuously maintain all
      mature blood cells, are regulated within the marrow microenvironment. We
      previously reported that pharmacologic treatment of naive mice with prostaglandin
      E2 (PGE2) expands HSPCs. However, the cellular mechanisms mediating this
      expansion remain unknown. Here, we demonstrate that PGE2 treatment in naive mice
      inhibits apoptosis of HSPCs without changing their proliferation rate. In a
      murine model of sublethal total body irradiation (TBI), in which HSPCs are
      rapidly lost, treatment with a long-acting PGE2 analog (dmPGE2) reversed the
      apoptotic program initiated by TBI. dmPGE2 treatment in vivo decreased the loss
      of functional HSPCs following radiation injury, as demonstrated both
      phenotypically and by their increased reconstitution capacity. The antiapoptotic
      effect of dmPGE2 on HSPCs did not impair their ability to differentiate in vivo,
      resulting instead in improved hematopoietic recovery after TBI. dmPGE2 also
      increased microenvironmental cyclooxygenase-2 expression and expanded the alpha
      smooth muscle actin-expressing subset of marrow macrophages, thus enhancing the
      bone marrow microenvironmental response to TBI. Therefore, in vivo treatment with
      PGE2 analogs may be particularly beneficial to HSPCs in the setting of injury by
      targeting them both directly and also through their niche. The current data
      provide rationale for in vivo manipulation of the HSPC pool as a strategy to
      improve recovery after myelosuppression.

PMID- 23169596
TI  - Epitrix flea beetles: new threats to potato production in Europe.
AB  - Epitrix tuberis and E. cucumeris are major pests of potatoes in North America. E.
      tuberis causes the most serious damage because the larval feeding can cause
      superficial serpentine tunnelling on the surface of tubers as well as deeper
      pits. This damage can make crops unmarketable. By contrast, E. cucumeris mainly
      damages the foliage, and yield losses can occur when the adults reach high
      densities. In 2004, potato tuber damage characteristic of E. tuberis was seen in
      Portugal. In 2008, damage was more widespread and severe. E. cucumeris and a
      lesser known species, E. similaris, were recorded in affected fields. E.
      similaris has since been found across Galicia, Spain. E. similaris is thought to
      be the most likely cause of the tuber damage in Portugal, but it is possible that
      E. cucumeris or an as yet undetected Epitrix species is causing the damage. In
      2010, a pest risk assessment for the Euro-Mediterranean area identified the
      movement of adults and pupae with seed or ware potatoes and associated soil as
      being the highest-risk pathways for the spread of Epitrix. In 2012, EU emergency
      measures were agreed to reduce the risk of further introductions and the rate of
      spread of these pests.

PMID- 23169597
TI  - Sleep disordered breathing in patients with primary ciliary dyskinesia.
AB  - BACKGROUND: Upper airway manifestations of primary ciliary dyskinesia (PCD) can
      cause obstructive sleep apnea syndrome (OSAS). Also abnormalities of lung
      mechanics and gas exchange may lead to sleep abnormalities in these patients.
      OBJECTIVES: To determine the rate of OSAS and sleep quality in PCD patients, and
      whether these are related to upper respiratory system manifestations and severity
      of lung disease in these patients. METHODS: Twenty-nine PCD patients and healthy
      controls were included to the study. Respiratory symptoms within the previous
      month were separately scored with the severity of the symptoms. Physical
      examination, pulmonary function tests, and ear-nose-throat assessments were
      obtained. All patients completed the Turkish version of Pittsburgh Sleep Quality
      Index (PSQI), sleep questionnaire, and underwent overnight polysomnography.
      Categorical variables were compared with chi-square and Fisher's exact test while
      continuous variables were compared with Student's t-test. RESULTS: Eleven PCD
      patients reported themselves to be "poor" sleepers, compared to only one subject
      in the control group (P = 0.002). Sixty-five percent of PCD patients had habitual
      snoring (HS). Fifty-two percent of the PCD patients had OSAS in polysomnography.
      OSAS rate was higher in PCD patients who snored (P = 0.008). HS and OSAS were
      more common in PCD patients who had cigarette smoke exposure in their homes (P <
      0.001 and P = 0.02, respectively). CONCLUSIONS: Patients with PCD have decreased
      sleep quality and higher rate of sleep disordered breathing compared to controls
      and higher rate of OSAS compared to population rates. Cigarette smoke exposure is
      an important risk factor for OSAS in PCD patients. Assessment and treatment of
      sleep disorders in PCD should be a part of disease management. Periodicals, Inc.

PMID- 23169598
TI  - Periostin may play a protective role in the development of eosinophilic chronic
      rhinosinusitis with nasal polyps in a mouse model.
AB  - OBJECTIVES/HYPOTHESIS: Several genes have been reported to be upregulated in
      human nasal polyps in previous genetic analyses. Among these genes, periostin is
      known to be overexpressed in nasal polyps obtained from aspirin-sensitive
      patients. Using periostin-null mice, we investigated the role of periostin in a
      murine model of eosinophilic rhinosinusitis with nasal polyps. STUDY DESIGN:
      Animal study. METHODS: Eosinophilic rhinosinusitis was induced in both periostin
      null and wild-type mice according to previously established protocols. In brief,
      ovalbumin (OVA) was used for sensitization and prolonged intranasal stimulation.
      Staphylococcus aureus enterotoxin B was applied intranasally to develop polyplike
      lesions. To examine the inflammation and mucosal lesions, hematoxylin and eosin,
      Sirius red, and Giemsa staining were performed. RESULTS: There was no definite
      difference in the maximal mucosal thickness between periostin-null and wild-type
      mice. In contrast, some parameters of inflammation, including the number of
      polyplike lesions and mast cells, were aggravated in the periostin-null mice
      compared to wild type. Eosinophilic infiltration was aggravated in the OVA
      stimulated periostin-null mice, compared to OVA-stimulated wild-type mice,
      whereas there was no apparent difference between wild-type and periostin-null
      mice challenged with additional S aureus enterotoxin B. CONCLUSIONS: The loss of
      periostin appears to enhance polyplike lesion formation and mast cell
      infiltration in a mouse model of eosinophilic rhinosinusitis with nasal polyps.

PMID- 23169599
TI  - A common diaryl ether intermediate for the gram-scale synthesis of oxazine and
      xanthene fluorophores.
AB  - Common ground: copper-catalyzed coupling reactions can be used for the high
      yielding preparation of widely used oxazine and xanthene fluorophores from a
      common diaryl ether intermediate on a gram-scale. This general approach may
      facilitate the future development of novel fluorophores and probes with unique
      properties.

PMID- 23169600
TI  - Spontaneous hemopneumothorax simulating acute abdominal affections.
AB  - Spontaneous hemopneumothorax (SHP) is a rare potentially life-threatening
      condition that occurs in predominantly young adolescents. The resultant massive
      hemorrhage leading to hypovolemic shock can be a surgical emergency. It
      constitutes 1-12% of all spontaneous pneumothoraces and presents with two
      cardinal features, chest pain and dyspnea. However, the pain of SHP may be
      confined to the abdomen secondary to the irritation of diaphragmatic pleura,
      which produces signs simulating an acute abdomen. SHP masquerading as an
      abdominal affection is apparently regarded as extremely rare. We present a case
      of a 16-year-old male with SHP presenting features simulating acute gallbladder
      disease. After prompt diagnosis with appropriate surgical intervention, he had an
      uneventful recovery. Our experience emphasizes the importance of careful and
      thorough chest examination for each child with atypical pictures for abdominal
      pain to exclude possible extra-abdominal lesions, even rare as SHP.

PMID- 23169602
TI  - Total soft palate reconstruction using the palatal island and lateral pharyngeal
      wall flaps.

PMID- 23169601
TI  - Muscle phenotype in patients with myotonic dystrophy type 1.
AB  - INTRODUCTION: The pathogenesis of muscle involvement in patients with myotonic
      dystrophy type 1 (DM1) is not well understood. In this study, we characterized
      the muscle phenotype in patients with confirmed DM1. METHODS: In 38 patients,
      muscle strength was tested by hand-held dynamometry. Myotonia was evaluated by a
      handgrip test and by analyzing the decrement of the compound muscle action
      potential. Muscle biopsies were assessed for morphological changes and Na(+)-K(+)
      pump content. RESULTS: Muscle strength correlated with a decline in Na(+)-K(+)
      pump content (r = 0.60, P < 0.001) and with CTG expansion. CTG expansion did not
      correlate with severity of myotonia, proximal histopathological changes, or Na(+)
      K(+) pump content. Histopathologically, we found few centrally placed nuclei
      (range 0.2-6.9%). CONCLUSIONS: The main findings of this study are that muscle
      weakness correlated inversely with CTG expansion and that central nuclei are not
      a prominent feature of proximal muscles in DM1.

PMID- 23169603
TI  - Birth defects surveillance: an essential public health function for primary
      prevention and health promotion.

PMID- 23169604
TI  - Combinatorial on-chip study of miniaturized 3D porous scaffolds using a patterned
      superhydrophobic platform.
AB  - One of the main challenges in tissue engineering (TE) is to obtain optimized
      products, combining biomaterials, cells and soluble factors able to stimulate
      tissue regeneration. Multiple combinations may be considered by changing the
      conditions among these three factors. The unpredictable response of each
      combination requires time-consuming tests. High-throughput methodologies have
      been proposed to master such complex analyses in TE. Usually, these tests are
      performed using cells cultured into 2D biomaterials or by dispensing arrays of
      cell-loaded hydrogels. For the first time an on-chip combinatorial study of 3D
      miniaturized porous scaffolds is proposed, using a patterned bioinspired
      superhydrophobic platform. Arrays of biomaterials are dispensed and processed in
      situ as porous scaffolds with distinct composition, surface characteristics,
      porosity/pore size, and mechanical properties. On-chip porosity, pore size, and
      mechanical properties of scaffolds based on chitosan and alginate are assessed by
      adapting microcomputed tomography equipment and a dynamic mechanical analyzer, as
      well as cell response after 24 hours. The interactions between cell types of two
      distinct origins-osteoblast-like and fibroblasts-and the scaffolds modified with
      fibronectin are studied and validated by comparison with conventional destructive
      methods (dsDNA quantification and MTS tests). Physical and biological on-chip
      analyses are coherent with the conventional measures, and conclusions about the
      most favorable conditions for each cell type are taken.

PMID- 23169605
TI  - Concise review: Bone marrow meets blastocyst: lessons from an unlikely encounter.
AB  - This article discusses the implications of the recent discovery that rat bone
      marrow-derived multipotent adult progenitor cells (rMAPCs), a cell type with
      broad somatic differentiation potential but of uncertain lineage identity, are
      similar to rat blastocyst-derived extraembryonic endoderm precursor (rXENP)
      cells, which appear to represent the committed extraembryonic endoderm precursor
      of the blastocyst. It was found that under rMAPC culture conditions, rXENP cells
      can be homogeneously cultured and similar cells, named rat hypoblast stem cells
      (rHypoSCs), can be derived from rat blastocysts more rapidly and directly. The
      detailed comparison of rHypoSCs, rXENP cells, and rMAPCs revealed highly similar
      gene expression profiles and developmental potentials. The significance of these
      findings for embryology, stem cell biology, and medicine is discussed.
      Specifically, the results assign a lineage identity to rMAPCs, indicate that
      rMAPCs originated by environmental reprogramming, and imply that HypoSCs, XENP
      cells, and MAPCs possess lineage plasticity. The MAPC-HypoSC relation also
      strengthens the consistency of rat and mouse embryology and consequently the idea
      that HypoSCs represent the committed extraembryonic endoderm precursor of the
      blastocyst. On this basis, it is argued that the direct comparison of HypoSCs
      (now available in pure form) with embryonic stem cells will be highly useful for
      the understanding of pluripotency and plasticity. Finally, the new findings
      suggest an explanation for an obscure observation on stem cell-induced
      transplantation tolerance. Thus, the HypoSC/XENP/MAPC phenotype provides a unique
      but broadly instructive model with which to study stem cell plasticity,
      reprogramming, and transplantation tolerance, all central themes in regenerative
      medicine.

PMID- 23169606
TI  - Why is gold such a good catalyst for oxygen reduction in alkaline media?
AB  - The two faces of gold: the reduction of oxygen on gold electrodes in alkaline
      solutions has been investigated theoretically. The most favorable reaction leads
      directly to adsorbed O(2)(-), but the activation energy for a two-step pathway,
      in which the first step is an outer-sphere electron transfer to give solvated
      O(2)(-), is only slightly higher. d-band catalysis, which dominates oxygen
      reduction in acid media, plays no role. The reason why the reaction is slow in
      acid media is also explained.

PMID- 23169607
TI  - A single ascending-dose study of muscle regulator ACE-031 in healthy volunteers.
AB  - INTRODUCTION: ACE-031 is a soluble form of activin receptor type IIB (ActRIIB).
      ACE-031 promotes muscle growth by binding to myostatin and other negative
      regulators of muscle mass. METHODS: This double-blind, placebo-controlled study
      evaluated the safety, pharmacokinetics, and pharmacodynamics of ACE-031 in 48
      healthy, postmenopausal women randomized to receive 1 dose of ACE-031 (0.02-3
      mg/kg s.c.) or placebo (3:1). RESULTS: ACE-031 was generally well-tolerated.
      Adverse events included injection site erythema. Mean ACE-031 AUC(0-infinity) and
      C(max) increased linearly with dose; mean T(1/2) was 10-15 days. Statistically
      significant increases in mean total body lean mass (3.3%; P = 0.03, by DXA) and
      thigh muscle volume (5.1%; P = 0.03, by MRI) were observed at day 29 in the 3
      mg/kg group. Statistically significant changes in serum biomarkers suggest ACE
      031 also improved bone and fat metabolism. CONCLUSIONS: Single-dose ACE-031
      treatment was generally well-tolerated and resulted in increases in muscle mass
      in healthy postmenopausal women.

PMID- 23169608
TI  - Metabolism and pharmacokinetics of 3-n-butylphthalide (NBP) in humans: the role
      of cytochrome P450s and alcohol dehydrogenase in biotransformation.
AB  - 3-n-Butylphthalide (NBP) is a cardiovascular drug currently used for the
      treatment of cerebral ischemia. The present study aims to investigate the
      metabolism, pharmacokinetics, and excretion of NBP in humans and identify the
      enzymes responsible for the formation of major metabolites. NBP underwent
      extensive metabolism after an oral administration of 200 mg NBP and 23
      metabolites were identified in human plasma and urine. Principal metabolic
      pathways included hydroxylation on alkyl side chain, particularly at 3-, omega-1
      , and omega-carbons, and further oxidation and conjugation. Approximately 81.6%
      of the dose was recovered in urine, mainly as NBP-11-oic acid (M5-2) and
      glucuronide conjugates of M5-2 and mono-hydroxylated products. 10-Keto-NBP (M2),
      3-hydroxy-NBP (M3-1), 10-hydroxy-NBP (M3-2), and M5-2 were the major circulating
      metabolites, wherein the areas under the curve values were 1.6-, 2.9-, 10.3-, and
      4.1-fold higher than that of NBP. Reference standards of these four metabolites
      were obtained through microbial biotransformation by Cunninghamella blakesleana.
      In vitro phenotyping studies demonstrated that multiple cytochrome P450 (P450)
      isoforms, especially CYP3A4, 2E1, and 1A2, were involved in the formation of M3
      1, M3-2, and 11-hydroxy-NBP. Using M3-2 and 11-hydroxy-NBP as substrates, human
      subcellular fractions experiments revealed that P450, alcohol dehydrogenase, and
      aldehyde dehydrogenase catalyzed the generation of M2 and M5-2. Formation of M5-2
      was much faster than that of M2, and M5-2 can undergo beta-oxidation to yield
      phthalide-3-acetic acid in rat liver homogenate. Overall, our study demonstrated
      that NBP was well absorbed and extensively metabolized by multiple enzymes to
      various metabolites prior to urinary excretion.

PMID- 23169609
TI  - Pharmacokinetics, metabolism, and excretion of the antidiabetic agent
      ertugliflozin (PF-04971729) in healthy male subjects.
AB  - The disposition of ertugliflozin (PF-04971729), an orally active selective
      inhibitor of the sodium-dependent glucose cotransporter 2, was studied after a
      single 25-mg oral dose of [(14)C]-ertugliflozin to healthy human subjects. Mass
      balance was achieved with approximately 91% of the administered dose recovered in
      urine and feces. The total administered radioactivity excreted in feces and urine
      was 40.9% and 50.2%, respectively. The absorption of ertugliflozin in humans was
      rapid with a T(max) at ~1.0 hour. Of the total radioactivity excreted in feces
      and urine, unchanged ertugliflozin collectively accounted for ~35.3% of the dose,
      suggestive of moderate metabolic elimination in humans. The principal
      biotransformation pathway involved glucuronidation of the glycoside hydroxyl
      groups to yield three regioisomeric metabolites, M4a, M4b, and M4c (~39.3% of the
      dose in urine), of which M4c was the major regioisomer (~31.7% of the dose). The
      structure of M4a and M4c were confirmed to be ertugliflozin -4-O-beta- and -3-O
      beta-glucuronide, respectively, via comparison of the HPLC retention time and
      mass spectra with authentic standards. A minor metabolic fate involved oxidation
      by cytochrome P450 to yield monohydroxylated metabolites M1 and M3 and des-ethyl
      ertugliflozin (M2), which accounted for ~5.2% of the dose in excreta. In plasma,
      unchanged ertugliflozin and the corresponding 4-O-beta- (M4a) and 3-O-beta- (M4c)
      glucuronides were the principal components, which accounted for 49.9, 12.2, and
      24.1% of the circulating radioactivity. Overall, these data suggest that
      ertugliflozin is well absorbed in humans, and eliminated largely via
      glucuronidation.

PMID- 23169610
TI  - The role of cytochrome P450-dependent metabolism in the regulation of mouse
      hepatic growth hormone signaling components and target genes by 3
      methylcholanthrene.
AB  - 3-Methylcholanthrene (MC) is a readily metabolized aryl hydrocarbon receptor
      (AHR) agonist. MC disrupts expression of mouse hepatic growth hormone (GH)
      signaling components and suppresses cytochrome P450 2D9 (Cyp2d9), a male-specific
      gene controlled by pulsatile GH via signal transducer and activator of
      transcription 5b (STAT5b). To determine if these effects of MC depend on hepatic
      microsomal P450-mediated activity, we examined biologic responses to MC treatment
      in liver Cpr-null (LCN) mice with hepatocyte-specific conditional deletion of
      NADPH-cytochrome P450 oxidoreductase (POR). MC caused mild induction of Por and a
      hepatic inflammatory marker in wild-type mice, whereas MC caused strong induction
      of AHR target genes, Cyp1a1, Cyp1a2, and Cyp1b1 in wild-type and LCN mice. Two
      mouse hepatic STAT5b target genes, Cyp2d9 and major urinary protein 2 (Mup2),
      were suppressed by MC in wild-type mice, and the CYP2D9 mRNA response was
      maintained in LCN mice. In wild-type mice only, MC decreased hepatic GH receptor
      (GHR) mRNA but increased GHR protein levels. There was an apparent impairment of
      STAT5 phosphorylation by MC in wild-type and LCN mice, but large interanimal
      variation prevented achievement of statistical significance. In vehicle-treated
      mice, basal levels of MUP2 mRNA, GHR mRNA, GHR protein, and the activation status
      of extracellular signal-regulated kinase 2 and Akt were influenced by hepatic Por
      genetic status. These results indicate that the effects of MC on hepatic GH
      signaling components and target genes are complex, involving aspects that are
      both dependent and independent of hepatic microsomal P450-mediated activity.

PMID- 23169612
TI  - Chest CT in bronchopulmonary dysplasia: clinical and radiological correlations.
AB  - BACKGROUND: Chest CT is very sensitive in assessing pulmonary damage in
      bronchopulmonary dysplasia (BPD) and radiological findings in BPD are well
      described. Validated CT scores are available to assess BPD, as available in other
      pulmonary diseases such as cystic fibrosis. AIM: To investigate whether there is
      a correlation between radiological pulmonary lesions and relevant BPD clinical
      data (gestational age, type and duration of mechanical ventilation, and severity
      of BPD) and assess the usefulness of a CT score in evaluating clinical severity.
      MATERIALS AND METHODS: Retrospective study of 19 premature infants with BPD born
      between 1998 and 2007 who underwent at least one chest CT during their first year
      of life. A total of 29 CT were blindly evaluated by two radiologists for the
      presence or absence of pulmonary parenchymal abnormalities described in BPD
      (areas of decreased attenuation, presence of bullae/emphysema, bronchial wall
      thickening, bronchiectasis, linear, and subpleural opacities). This score was
      then compared with the most relevant clinical data. RESULTS: All CT scans showed
      abnormalities. The most frequent lesion was bronchial wall thickening observed in
      all patients, followed by linear (89.5%) and subpleural (89.5%) opacities. Areas
      of decreased attenuation were found in 68.4%. Bullae/emphysema and bronchiectasis
      were the less frequent item described (26.3% and 21.1%, respectively). The
      presence of areas of decreased attenuation significantly correlated with BPD
      severity (P = 0.03). However, there was no significant correlation between the CT
      score and clinical data. CONCLUSIONS: This study demonstrates the potential
      usefulness of chest CT score to assess the severity of BPD. Areas of decreased
      attenuation seem the most sensitive item to predict BPD severity. More patients
      are needed to validate this approach and to evaluate the long-term usefulness of
      CT scan.

PMID- 23169611
TI  - Immunohistochemical and functional characterization of peptide, organic cation,
      neutral and basic amino acid, and monocarboxylate drug transporters in human
      ocular tissues.
AB  - Since there is paucity of information on solute transporters in human ocular
      tissues, the aim of this study was immunohistochemical and functional
      characterization of peptide transporters (PEPT), organic cation transporters
      (OCTs), neutral and basic amino acid transporters (ATB(0,+)), and monocarboxylate
      transporters (MCTs) in human ocular barriers. Immunohistochemical localization of
      transporters was achieved using 5-um-thick paraffin-embedded sections of whole
      human eyes. In vitro transport studies were carried out across human cornea and
      sclera-choroid-retinal pigment epithelium (SCRPE) using a cassette of specific
      substrates in the presence and absence of inhibitors to determine the role of
      transporters in transtissue solute delivery. Immunohistochemistry showed the
      expression of PEPT-1, PEPT-2, ATB(0,+), OCT-1, OCT-2, MCT-1, and MCT-3 in human
      ocular tissues. PEPT-1, PEPT-2, OCT-1, MCT-1, and ATB(0,+) expression was evident
      in the cornea, conjunctiva, ciliary epithelium, and neural retina. Expression of
      PEPT-1, PEPT-2, and OCT-1 was evident in choroid tissue as well. OCT-2 expression
      could be seen in the corneal and conjunctival epithelia, whereas MCT-3 expression
      was confined to the RPE layer. OCT-2 expression was evident in conjunctival blood
      vessel walls, whereas PEPT-1, PEPT-2, and OCT-1 were expressed in the choroid.
      Preliminary transport studies indicated inward transport of Gly-Sar (PEPT
      substrate), 1-methyl-4-phenylpyridinium (MPP+) (OCT substrate), and l-tryptophan
      (ATB(0,+) substrate) across cornea as well as SCRPE. For phenylacetic acid (MCT
      substrate), transporter-mediated inward transport across the cornea and outward
      transport across SCRPE were evident. Thus, PEPT, OCT, and ATB(0,+) are influx
      transporters present in human ocular barriers, and they can potentially be used
      for transporter-guided retinal drug delivery after topical, transscleral, and
      systemic administrations.

PMID- 23169613
TI  - Embryotoxicity of Psoralea corylifolia L.: in vivo and in vitro studies.
AB  - BACKGROUND: Psoralea corylifolia L. (PC) was commonly used to treat miscarriages
      clinically. The aim of this study was to examine its embryotoxicity in mice and
      embryonic stem cells (ESCs). METHODS: Quality control of PC extract including
      reference marker compounds, pesticide residues, and heavy metals was
      authenticated with HPLC, Gas chromatography-mass spectrometry (GC-MS), and
      inductively coupled plasma-mass spectrometry. Pregnant mice were randomly
      assigned into five groups and dosed with distilled water (G1), PC extract of 2
      (G2), 4 (G3), or 8 g/kg/day (G4), and vitamin A (G5). Meanwhile, half maximal
      inhibitory concentration values for ESCs and 3T3 cells were identified in a
      cytotoxicity assay, and apoptosis in neuroepithelium was assessed by transmission
      electron microscopy. RESULTS: In the G4 group, a statistically significant
      decrease in the total fetus, live fetus, and gravid uterine weight, and increase
      in the resorbed fetus, postimplantation loss, and neuroepithelial apoptosis as
      well as maternal liver-weight were found (p < 0.05). CONCLUSIONS: PC extracts at
      8 g/kg/day might cause fetal toxicity and maternal liver damage in mice, although
      it did not cause typical malformation and ESC's cytotoxicity in this experiment.
      Our data suggested that high dosage and long-term administration of PC
      preparations may not be safe for pregnant women.

PMID- 23169614
TI  - How do the electrical properties of graphene change with its functionalization?
AB  - Functionalization of graphene is essential to interface it with other moieties to
      expand the scope of its electrical/electronic applications. However, chemical
      functionalization and/or molecular interactions on graphene sensitively modulate
      its electrical properties. To evaluate and take advantage of the properties of
      functionalized graphene, it is important to understand how its electrical
      attributes (such as carrier scattering, carrier concentration, charge polarity,
      quantum-capacitance enhanced doping, energy levels, transport mechanisms, and
      orbital hybridization of energy-bands) are influenced by a change in carbon's
      structural conformation, hybridization state, chemical potential, local energy
      levels, and dopant/interface coupling induced via functionalization or molecular
      interactions. Here, a detailed and integrated model describes factors influencing
      these electrical characteristics of functionalized graphene (covalent bonds,
      adsorption, pi-pi bonds, and lattice incorporation). The electrical properties
      are governed via three mechanisms: (a) conversion of carbon's hybridized state,
      (b) dipole interactions enhanced via quantum capacitance, and (c) orbital
      hybridization with an interfacing molecule. A few graphenic materials are also
      identified where further studies are essential to understand the effect of their
      functionalization.

PMID- 23169616
TI  - Dendritic fluoroalcohols as catalysts for alkene epoxidation with hydrogen
      peroxide.
AB  - Cooperativity is the key for mild catalytic epoxidation: the immobilization of
      fluoroalcohols on dendritic polyglycerol (by "click chemistry") provides
      organocatalysts that can form multiple hydrogen bonds. The epoxidation of alkenes
      with aqueous hydrogen peroxide proceeds efficiently in the presence of dendritic
      fluoroalcohol catalysts. The supported catalysts can be separated by membrane
      filtration and reused.

PMID- 23169615
TI  - Differentially activated macrophages orchestrate myogenic precursor cell fate
      during human skeletal muscle regeneration.
AB  - Macrophages (MPs) exert either beneficial or deleterious effects on tissue
      repair, depending on their activation/polarization state. They are crucial for
      adult skeletal muscle repair, notably by acting on myogenic precursor cells.
      However, these interactions have not been fully characterized. Here, we explored
      both in vitro and in vivo, in human, the interactions of differentially activated
      MPs with myogenic precursor cells (MPCs) during adult myogenesis and skeletal
      muscle regeneration. We showed in vitro that through the differential secretion
      of cytokines and growth factors, proinflammatory MPs inhibited MPC fusion while
      anti-inflammatory MPs strongly promoted MPC differentiation by increasing their
      commitment into differentiated myocytes and the formation of mature myotubes.
      Furthermore, the in vivo time course of expression of myogenic and MP markers was
      studied in regenerating human healthy muscle after damage. We observed that
      regenerating areas containing proliferating MPCs were preferentially associated
      with MPs expressing proinflammatory markers. In the same muscle, regenerating
      areas containing differentiating myogenin-positive MPCs were preferentially
      coupled to MPs harboring anti-inflammatory markers. These data demonstrate for
      the first time in human that MPs sequentially orchestrate adult myogenesis during
      regeneration of damaged skeletal muscle. These results support the emerging
      concept that inflammation, through MP activation, controls stem cell fate and
      coordinates tissue repair.

PMID- 23169617
TI  - Novel mutations in the Anoctamin 5 gene (ANO5) associated with limb-girdle
      muscular dystrophy 2L.
AB  - INTRODUCTION: We present a Jordanian man with the typical LGMD 2L phenotype of
      early, asymmetric quadriceps weakness and subsequent biceps brachii weakness.
      METHODS: Case report. RESULTS: Muscle biopsies document a progressive dystrophic
      pattern unrelated to known sarcolemmal defects associated with muscular
      dystrophy. Genetic testing revealed novel, heterozygote Anoctamin 5 gene
      mutations. CONCLUSIONS: This case report expands the known mutations resulting in
      LGMD 2L and supports the assertion that Anoctamin 5 mutations are more prevalent
      than previously recognized.

PMID- 23169618
TI  - Nasal epithelium biomarkers in young children: associations with allergic
      sensitization and environmental stressors.
AB  - BACKGROUND: Recent studies suggest that allergic diseases might have their onset
      in early epithelial barrier defects. To test this hypothesis, we assessed
      associations between nasal epithelium biomarkers, environmental stressors, and
      the risks of allergic sensitization. METHODS: In a cross-sectional study of 288
      kindergarten children (mean age, 5.7 years), we measured aeroallergen-specific
      IgE in nasal mucosa and the concentrations of urea, albumin, and Clara cell
      protein (CC16) in nasal lavage fluid (NALF). Albumin and CC16 in NALF were
      expressed per liter or as a ratio to urea. We also calculated the NALF
      CC16/albumin ratio as an index integrating the permeability and the secretory
      function of the nasal epithelium. RESULTS: Median NALF concentrations of CC16 and
      albumin were 8.2 ug/L and 34.5 mg/L, respectively. While there were no
      significant gender differences when proteins were expressed per liter, the CC16
      to albumin and CC16 to urea ratios in NALF were higher in girls than in boys (P =
      0.02 and 0.055, respectively. The nasal epithelial barrier function, as reflected
      by these NALF biomarkers, was positively influenced by probiotics and age, and
      negatively by environmental stressors such as pool chlorine. The risk of house
      dust mite (HDM) sensitization increased with decreasing log NALF CC16
      concentration, whether expressed per liter (2.59, 95% CI: 1.15-5.82, P = 0.02),
      as a ratio to urea (1.98, 95% CI: 0.96-4.06, P = 0.06), or as a ratio to albumin
      (OR, 2.03, 95% CI: 1.10-3.74, P = 0.02). Children in the highest and intermediate
      tertiles of the NALF albumin/urea ratio were three times more likely to be
      sensitized to HDM than those in the lowest tertile (both P = 0.04). CONCLUSION:
      Defects in the nasal epithelium barrier function of young children, as reflected
      by the concentrations of CC16 and albumin in NALF, are associated with
      environmental factors, including pool chlorine, and with increased risks of HDM
      sensitization.

PMID- 23169619
TI  - Transcription factor-dependent nuclear localization of a transcriptional
      repressor in jasmonate hormone signaling.
AB  - The plant hormone jasmonate (JA) plays an important role in regulating growth,
      development and immunity. A key step in JA signaling is ligand-dependent assembly
      of a coreceptor complex consisting of the F-box protein COI1 and JAZ
      transcriptional repressors. Assembly of this receptor complex results in
      proteasome-mediated degradation of JAZ repressors, which at resting state bind to
      and repress the MYC transcription factors. Although the JA receptor complex is
      believed to function within the nucleus, how this receptor complex enters the
      nucleus and, more generally, the cell biology of jasmonate signaling are not well
      understood. In this study, we conducted mutational analysis of the C termini
      (containing the conserved Jas motif) of two JAZ repressors, JAZ1 and JAZ9. These
      analyses unexpectedly revealed different subcellular localization patterns of
      JAZ1DeltaJas and JAZ9DeltaJas, which were associated with differential
      interaction of JAZ1DeltaJas and JAZ9DeltaJas with MYC2 and differential repressor
      activity in vivo. Importantly, physical interaction with MYC2 appears to play an
      active role in the nuclear targeting of JAZ1 and JAZ9, and the nuclear
      localization of JAZ9 was compromised in myc2 mutant plants. We identified a
      highly conserved arginine residue in the Jas motif that is critical for coupling
      MYC2 interaction with nuclear localization of JAZ9 and JAZ9 repressor function in
      vivo. Our results suggest a model for explaining why some JAZDeltaJas proteins,
      but not others, confer constitutive JA-insensitivity when overexpressed in
      plants. Results also provide evidence for a transcription factor-dependent
      mechanism for nuclear import of a cognate transcriptional repressor JAZ9 in
      plants.

PMID- 23169620
TI  - Ultrasensitivity of the Bacillus subtilis sporulation decision.
AB  - Starving Bacillus subtilis cells execute a gene expression program resulting in
      the formation of stress-resistant spores. Sporulation master regulator, Spo0A, is
      activated by a phosphorelay and controls the expression of a multitude of genes,
      including the forespore-specific sigma factor sigma(F) and the mother cell
      specific sigma factor sigma(E). Identification of the system-level mechanism of
      the sporulation decision is hindered by a lack of direct control over Spo0A
      activity. This limitation can be overcome by using a synthetic system in which
      Spo0A activation is controlled by inducing expression of phosphorelay kinase
      KinA. This induction results in a switch-like increase in the number of
      sporulating cells at a threshold of KinA. Using a combination of mathematical
      modeling and single-cell microscopy, we investigate the origin and physiological
      significance of this ultrasensitive threshold. The results indicate that the
      phosphorelay is unable to achieve a sufficiently fast and ultrasensitive response
      via its positive feedback architecture, suggesting that the sporulation decision
      is made downstream. In contrast, activation of sigma(F) in the forespore and of
      sigma(E) in the mother cell compartments occurs via a cascade of coherent feed
      forward loops, and thereby can produce fast and ultrasensitive responses as a
      result of KinA induction. Unlike sigma(F) activation, sigma(E) activation in the
      mother cell compartment only occurs above the KinA threshold, resulting in
      completion of sporulation. Thus, ultrasensitive sigma(E) activation explains the
      KinA threshold for sporulation induction. We therefore infer that under uncertain
      conditions, cells initiate sporulation but postpone making the sporulation
      decision to average stochastic fluctuations and to achieve a robust population
      response.

PMID- 23169621
TI  - Structural basis of mouse cytomegalovirus m152/gp40 interaction with RAE1gamma
      reveals a paradigm for MHC/MHC interaction in immune evasion.
AB  - Natural killer (NK) cells are activated by engagement of the NKG2D receptor with
      ligands on target cells stressed by infection or tumorigenesis. Several human and
      rodent cytomegalovirus (CMV) immunoevasins down-regulate surface expression of
      NKG2D ligands. The mouse CMV MHC class I (MHC-I)-like m152/gp40 glycoprotein down
      regulates retinoic acid early inducible-1 (RAE1) NKG2D ligands as well as host
      MHC-I. Here we describe the crystal structure of an m152/RAE1gamma complex and
      confirm the intermolecular contacts by mutagenesis. m152 interacts in a pincer
      like manner with two sites on the alpha1 and alpha2 helices of RAE1 reminiscent
      of the NKG2D interaction with RAE1. This structure of an MHC-I-like
      immunoevasin/MHC-I-like ligand complex explains the binding specificity of m152
      for RAE1 and allows modeling of the interaction of m152 with classical MHC-I and
      of related viral immunoevasins.

PMID- 23169622
TI  - Tcra gene recombination is supported by a Tcra enhancer- and CTCF-dependent
      chromatin hub.
AB  - Antigen receptor locus V(D)J recombination requires interactions between widely
      separated variable (V), diversity (D), and joining (J) gene segments, but the
      mechanisms that generate these interactions are not well understood. Here we
      assessed mechanisms that direct developmental stage-specific long-distance
      interactions at the Tcra/Tcrd locus. The Tcra/Tcrd locus recombines Tcrd gene
      segments in CD4(-)CD8(-) double-negative thymocytes and Tcra gene segments in
      CD4(+)CD8(+) double-positive thymocytes. Initial V(alpha)-to-J(alpha)
      recombination occurs within a chromosomal domain that displays a contracted
      conformation in both thymocyte subsets. We used chromosome conformation capture
      to demonstrate that the Tcra enhancer (E(alpha)) interacts directly with V(alpha)
      and J(alpha) gene segments distributed across this domain, specifically in double
      positive thymocytes. Moreover, E(alpha) promotes interactions between these
      V(alpha) and J(alpha) segments that should facilitate their synapsis. We found
      that the CCCTC-binding factor (CTCF) binds to E(alpha) and to many locus
      promoters, biases E(alpha) to interact with these promoters, and is required for
      efficient V(alpha)-J(alpha) recombination. Our data indicate that E(alpha) and
      CTCF cooperate to create a developmentally regulated chromatin hub that supports
      V(alpha)-J(alpha) synapsis and recombination.

PMID- 23169623
TI  - Relation between anaerobic inactivation and oxygen tolerance in a large series of
      NiFe hydrogenase mutants.
AB  - Nickel-containing hydrogenases, the biological catalysts of     oxidation and
      production, reversibly inactivate under anaerobic, oxidizing conditions. We aim
      at understanding the mechanism of (in)activation and what determines its
      kinetics, because there is a correlation between fast reductive reactivation and
      oxygen tolerance, a property of some hydrogenases that is very desirable from the
      point of view of biotechnology. Direct electrochemistry is potentially very
      useful for learning about the redox-dependent conversions between active and
      inactive forms of hydrogenase, but the voltammetric signals are complex and often
      misread. Here we describe simple analytical models that we used to characterize
      and compare 16 mutants, obtained by substituting the position-74 valine of the   
      -sensitive NiFe hydrogenase from Desulfovibrio fructosovorans. We observed that
      this substitution can accelerate reactivation up to 1,000-fold, depending on the
      polarity of the position 74 amino acid side chain. In terms of kinetics of
      anaerobic (in)activation and oxygen tolerance, the valine-to-histidine mutation
      has the most spectacular effect: The V74H mutant compares favorably with the    
      tolerant hydrogenase from Aquifex aeolicus, which we use here as a benchmark.

PMID- 23169624
TI  - Architectural switch in plant photosynthetic membranes induced by light stress.
AB  - Unavoidable side reactions of photosynthetic energy conversion can damage the
      water-splitting photosystem II (PSII) holocomplex embedded in the thylakoid
      membrane system inside chloroplasts. Plant survival is crucially dependent on an
      efficient molecular repair of damaged PSII realized by a multistep repair cycle.
      The PSII repair cycle requires a brisk lateral protein traffic between stacked
      grana thylakoids and unstacked stroma lamellae that is challenged by the tight
      stacking and low protein mobility in grana. We demonstrated that high light
      stress induced two main structural changes that work synergistically to improve
      the accessibility between damaged PSII in grana and its repair machinery in
      stroma lamellae: lateral shrinkage of grana diameter and increased protein
      mobility in grana thylakoids. It follows that high light stress triggers an
      architectural switch of the thylakoid network that is advantageous for swift
      protein repair. Studies of the thylakoid kinase mutant stn8 and the double mutant
      stn7/8 demonstrate the central role of protein phosphorylation for the structural
      alterations. These findings are based on the elaboration of mathematical tools
      for analyzing confocal laser-scanning microscopic images to study changes in the
      sophisticated thylakoid architecture in intact protoplasts.

PMID- 23169625
TI  - Stochastic geometry and topology of non-Gaussian fields.
AB  - Gaussian random fields pervade all areas of science. However, it is often the
      departures from Gaussianity that carry the crucial signature of the nonlinear
      mechanisms at the heart of diverse phenomena, ranging from structure formation in
      condensed matter and cosmology to biomedical imaging. The standard test of non
      Gaussianity is to measure higher-order correlation functions. In the present
      work, we take a different route. We show how geometric and topological properties
      of Gaussian fields, such as the statistics of extrema, are modified by the
      presence of a non-Gaussian perturbation. The resulting discrepancies give an
      independent way to detect and quantify non-Gaussianities. In our treatment, we
      consider both local and nonlocal mechanisms that generate non-Gaussian fields,
      both statically and dynamically through nonlinear diffusion.

PMID- 23169626
TI  - A ribosome-specialized translation initiation pathway is required for cap
      dependent translation of vesicular stomatitis virus mRNAs.
AB  - Initiation is the primary target of translational control for all organisms.
      Regulation of eukaryotic translation is traditionally thought to occur through
      initiation factors and RNA structures. Here, we characterize a transcript
      specific translation initiation mechanism that is mediated by the ribosome. By
      studying vesicular stomatitis virus (VSV), we identify the large ribosomal
      subunit protein rpL40 as requisite for VSV cap-dependent translation but not bulk
      cellular or internal ribosome entry site-driven translation. This requirement is
      conserved among members of the order Mononegavirales, including measles virus and
      rabies virus. Polysome analyses and in vitro reconstitution of initiation
      demonstrate that rpL40 is required for 80S formation on VSV mRNAs through a cis
      regulatory element. Using deep sequencing, we further uncover a subset of
      cellular transcripts that are selectively sensitive to rpL40 depletion,
      suggesting VSV may have usurped an endogenous translation pathway. Together,
      these findings demonstrate that the ribosome acts as a translational regulator
      outside of its catalytic role during protein synthesis.

PMID- 23169627
TI  - Estimating the influence of life satisfaction and positive affect on later income
      using sibling fixed effects.
AB  - The question of whether there is a connection between income and psychological
      well-being is a long-studied issue across the social, psychological, and
      behavioral sciences. Much research has found that richer people tend to be
      happier. However, relatively little attention has been paid to whether happier
      individuals perform better financially in the first place. This possibility of
      reverse causality is arguably understudied. Using data from a large US
      representative panel, we show that adolescents and young adults who report higher
      life satisfaction or positive affect grow up to earn significantly higher levels
      of income later in life. We focus on earnings approximately one decade after the
      person's well-being is measured; we exploit the availability of sibling clusters
      to introduce family fixed effects; we account for the human capacity to imagine
      later socioeconomic outcomes and to anticipate the resulting feelings in current
      well-being. The study's results are robust to the inclusion of controls such as
      education, intelligence quotient, physical health, height, self-esteem, and later
      happiness. We consider how psychological well-being may influence income. Sobel
      Goodman mediation tests reveal direct and indirect effects that carry the
      influence from happiness to income. Significant mediating pathways include a
      higher probability of obtaining a college degree, getting hired and promoted,
      having higher degrees of optimism and extraversion, and less neuroticism.

PMID- 23169629
TI  - Effects of sex and COMT genotype on environmentally modulated cognitive control
      in mice.
AB  - Cognitive functioning differs between males and females, likely in part related
      to genetic dimorphisms. An example of a common genetic variation reported to have
      sexually dimorphic effects on cognition and temperament in humans is the Val/Met
      polymorphism in catechol-O-methyltransferase (COMT). We tested male and female
      wild-type mice ((+/+)) and their COMT knockout littermates ((+/-) and (-/-)) in
      the five-choice serial reaction time task (5CSRTT) to investigate the effects of
      sex, COMT genotype, and their interactions with environmental manipulations of
      cognitive functions such as attention, impulsivity, compulsivity, motivation, and
      rule-reversal learning. No sex- or COMT-dependent differences were present in the
      basic acquisition of the five-choice serial reaction time task. In contrast,
      specific environmental manipulations revealed a variety of sex- and COMT
      dependent effects. Following an experimental change to trigger impulsive
      responding, the sexes showed similar increases in impulsiveness, but males
      eventually habituated whereas females did not. Moreover, COMT knockout mice were
      more impulsive compared with wild-type littermates. Manipulations involving mild
      stress adversely affected cognitive performance in males, and particularly COMT
      knockout males, but not in females. In contrast, following amphetamine treatment,
      subtle sex by genotype and sex by treatment interactions emerged primarily
      limited to compulsive behavior. After repeated testing, female mice showed
      improved performance, working harder and eventually outperforming males. Finally,
      removing the food-restriction condition enhanced sex and COMT differences,
      revealing that overall, females outperform males and COMT knockout males
      outperform their wild-type littermates. These findings illuminate complex sex-
      and COMT-related effects and their interactions with environmental factors to
      influence specific executive cognitive domains.

PMID- 23169628
TI  - Long-term influence of normal variation in neonatal characteristics on human
      brain development.
AB  - It is now recognized that a number of cognitive, behavioral, and mental health
      outcomes across the lifespan can be traced to fetal development. Although the
      direct mediation is unknown, the substantial variance in fetal growth, most
      commonly indexed by birth weight, may affect lifespan brain development. We
      investigated effects of normal variance in birth weight on MRI-derived measures
      of brain development in 628 healthy children, adolescents, and young adults in
      the large-scale multicenter Pediatric Imaging, Neurocognition, and Genetics
      study. This heterogeneous sample was recruited through geographically dispersed
      sites in the United States. The influence of birth weight on cortical thickness,
      surface area, and striatal and total brain volumes was investigated, controlling
      for variance in age, sex, household income, and genetic ancestry factors. Birth
      weight was found to exert robust positive effects on regional cortical surface
      area in multiple regions as well as total brain and caudate volumes. These
      effects were continuous across birth weight ranges and ages and were not confined
      to subsets of the sample. The findings show that (i) aspects of later child and
      adolescent brain development are influenced at birth and (ii) relatively small
      differences in birth weight across groups and conditions typically compared in
      neuropsychiatric research (e.g., Attention Deficit Hyperactivity Disorder,
      schizophrenia, and personality disorders) may influence group differences
      observed in brain parameters of interest at a later stage in life. These findings
      should serve to increase our attention to early influences.

PMID- 23169630
TI  - Self-boosting vaccines and their implications for herd immunity.
AB  - Advances in vaccine technology over the past two centuries have facilitated far
      reaching impact in the control of many infections, and today's emerging vaccines
      could likewise open new opportunities in the control of several diseases. Here we
      consider the potential, population-level effects of a particular class of
      emerging vaccines that use specific viral vectors to establish long-term,
      intermittent antigen presentation within a vaccinated host: in essence, "self
      boosting" vaccines. In particular, we use mathematical models to explore the
      potential role of such vaccines in situations where current immunization raises
      only relatively short-lived protection. Vaccination programs in such cases are
      generally limited in their ability to raise lasting herd immunity. Moreover, in
      certain cases mass vaccination can have the counterproductive effect of allowing
      an increase in severe disease, through reducing opportunities for immunity to be
      boosted through natural exposure to infection. Such dynamics have been proposed,
      for example, in relation to pertussis and varicella-zoster virus. In this context
      we show how self-boosting vaccines could open qualitatively new opportunities,
      for example by broadening the effective duration of herd immunity that can be
      achieved with currently used immunogens. At intermediate rates of self-boosting,
      these vaccines also alleviate the potential counterproductive effects of mass
      vaccination, through compensating for losses in natural boosting. Importantly,
      however, we also show how sufficiently high boosting rates may introduce a new
      regime of unintended consequences, wherein the unvaccinated bear an increased
      disease burden. Finally, we discuss important caveats and data needs arising from
      this work.

PMID- 23169631
TI  - Predicted structure of agonist-bound glucagon-like peptide 1 receptor, a class B
      G protein-coupled receptor.
AB  - The glucagon-like peptide 1 receptor (GLP1R) is a G protein-coupled receptor
      (GPCR) involved in insulin synthesis and regulation; therefore, it is an
      important drug target for treatment of diabetes. However, GLP1R is a member of
      the class B1 family of GPCRs for which there are no experimental structures. To
      provide a structural basis for drug design and to probe class B GPCR activation,
      we predicted the transmembrane (TM) bundle structure of GLP1R bound to the
      peptide Exendin-4 (Exe4; a GLP1R agonist on the market for treating diabetes)
      using the MembStruk method for scanning TM bundle conformations. We used protein
      protein docking methods to combine the TM bundle with the X-ray crystal structure
      of the 143-aa N terminus coupled to the Exe4 peptide. This complex was subjected
      to 28 ns of full-solvent, full-lipid molecular dynamics. We find 14 strong polar
      interactions of Exe4 with GLP1R, of which 8 interactions are in the TM bundle (2
      interactions confirmed by mutation studies) and 6 interactions involve the N
      terminus (3 interactions found in the crystal structure). We also find 10
      important hydrophobic interactions, of which 4 interactions are in the TM bundle
      (2 interactions confirmed by mutation studies) and 6 interactions are in the N
      terminus (6 interactions present in the crystal structure). Thus, our predicted
      structure agrees with available mutagenesis studies. We suggest a number of
      mutation experiments to further validate our predicted structure. The structure
      should be useful for guiding drug design and can provide a structural basis for
      understanding ligand binding and receptor activation of GLP1R and other class B1
      GPCRs.

PMID- 23169632
TI  - Perceptual convergence of multi-component mixtures in olfaction implies an
      olfactory white.
AB  - In vision, two mixtures, each containing an independent set of many different
      wavelengths, may produce a common color percept termed "white." In audition, two
      mixtures, each containing an independent set of many different frequencies, may
      produce a common perceptual hum termed "white noise." Visual and auditory whites
      emerge upon two conditions: when the mixture components span stimulus space, and
      when they are of equal intensity. We hypothesized that if we apply these same
      conditions to odorant mixtures, "whiteness" may emerge in olfaction as well. We
      selected 86 molecules that span olfactory stimulus space and individually diluted
      them to a point of about equal intensity. We then prepared various odorant
      mixtures, each containing various numbers of molecular components, and asked
      human participants to rate the perceptual similarity of such mixture pairs. We
      found that as we increased the number of nonoverlapping, equal-intensity
      components in odorant mixtures, the mixtures became more similar to each other,
      despite not having a single component in common. With ~30 components, most
      mixtures smelled alike. After participants were acquainted with a novel,
      arbitrarily named mixture of ~30 equal-intensity components, they later applied
      this name more readily to other novel mixtures of ~30 equal-intensity components
      spanning stimulus space, but not to mixtures containing fewer components or to
      mixtures that did not span stimulus space. We conclude that a common olfactory
      percept, "olfactory white," is associated with mixtures of ~30 or more equal
      intensity components that span stimulus space, implying that olfactory
      representations are of features of molecules rather than of molecular identity.

PMID- 23169633
TI  - Public good dynamics drive evolution of iron acquisition strategies in natural
      bacterioplankton populations.
AB  - A common strategy among microbes living in iron-limited environments is the
      secretion of siderophores, which can bind poorly soluble iron and make it
      available to cells via active transport mechanisms. Such siderophore-iron
      complexes can be thought of as public goods that can be exploited by local
      communities and drive diversification, for example by the evolution of
      "cheating." However, it is unclear whether bacterial populations in the
      environment form stable enough communities such that social interactions
      significantly impact evolutionary dynamics. Here we show that public good games
      drive the evolution of iron acquisition strategies in wild populations of marine
      bacteria. We found that within nonclonal but ecologically cohesive genotypic
      clusters of closely related Vibrionaceae, only an intermediate percentage of
      genotypes are able to produce siderophores. Nonproducers within these clusters
      exhibited selective loss of siderophore biosynthetic pathways, whereas
      siderophore transport mechanisms were retained, suggesting that these
      nonproducers can act as cheaters that benefit from siderophore producers in their
      local environment. In support of this hypothesis, these nonproducers in iron
      limited media suffer a significant decrease in growth, which can be alleviated by
      siderophores, presumably owing to the retention of transport mechanisms.
      Moreover, using ecological data of resource partitioning, we found that cheating
      coevolves with the ecological specialization toward association with larger
      particles in the water column, suggesting that these can harbor stable enough
      communities for dependencies among organisms to evolve.

PMID- 23169634
TI  - AtWRKY15 perturbation abolishes the mitochondrial stress response that steers
      osmotic stress tolerance in Arabidopsis.
AB  - Environmental stresses adversely affect plant growth and development. A common
      theme within these adverse conditions is the perturbation of reactive oxygen
      species (ROS) homeostasis. Here, we demonstrate that the ROS-inducible
      Arabidopsis thaliana WRKY15 transcription factor (AtWRKY15) modulates plant
      growth and salt/osmotic stress responses. By transcriptome profiling, a divergent
      stress response was identified in transgenic WRKY15-overexpressing plants that
      linked a stimulated endoplasmic reticulum-to-nucleus communication to a disrupted
      mitochondrial stress response under salt-stress conditions. We show that
      mitochondrial calcium-flux sensing might be important for regulating an active
      mitochondrial retrograde signaling and launching an appropriate defense response
      to confer salt-stress tolerance.

PMID- 23169635
TI  - Expression of plasma cell alloantigen 1 defines layered development of B-1a B
      cell subsets with distinct innate-like functions.
AB  - Innate-like B-1a cells contribute significantly to circulating natural antibodies
      and mucosal immunity as well as to immunoregulation. Here we show that these
      classic functions of B-1a cells segregate between two unique subsets defined by
      expression of plasma cell alloantigen 1 (PC1), also known as ectonucleotide
      pyrophosphatase phosphodiesterase 1 (ENPP1). These subsets, designated B
      1a.PC1(lo) and B-1a.PC1(hi), differ significantly in IgH chain utilization.
      Adoptively transferred PC1(lo) cells secreted significantly more circulating
      natural IgM and intestinal IgA than PC1(hi) cells. In contrast, PC1(hi) cells
      produced more IL-10 than PC1(lo) cells when stimulated with LPS and phorbol 12
      myristate 13-acetate (PMA). PC1(hi) cells were also more efficient than PC1(lo)
      cells in regulating Th1 cell differentiation, even though both B-1a subsets were
      comparably active in stimulating T-cell proliferation. Furthermore, PC1(lo) cells
      generated antigen-specific IgM responses to pneumococcal polysaccharide antigens,
      whereas PC1(hi) cells do not. We found that PC1(lo) cells develop from an early
      wave of B-1a progenitors in fetal life, whereas PC1(hi) cells are generated from
      a later wave after birth. We conclude that identification of B-1a.PC1(lo) and B
      1a.PC1(hi) cells extends the concept of a layered immune system with important
      implications for developing effective vaccines and promoting the generation of
      immunoregulatory B cells.

PMID- 23169637
TI  - Evidence for a midlife crisis in great apes consistent with the U-shape in human
      well-being.
AB  - Recently, economists and behavioral scientists have studied the pattern of human
      well-being over the lifespan. In dozens of countries, and for a large range of
      well-being measures, including happiness and mental health, well-being is high in
      youth, falls to a nadir in midlife, and rises again in old age. The reasons for
      this U-shape are still unclear. Present theories emphasize sociological and
      economic forces. In this study we show that a similar U-shape exists in 508 great
      apes (two samples of chimpanzees and one sample of orangutans) whose well-being
      was assessed by raters familiar with the individual apes. This U-shaped pattern
      or "midlife crisis" emerges with or without use of parametric methods. Our
      results imply that human well-being's curved shape is not uniquely human and
      that, although it may be partly explained by aspects of human life and society,
      its origins may lie partly in the biology we share with great apes. These
      findings have implications across scientific and social-scientific disciplines,
      and may help to identify ways of enhancing human and ape well-being.

PMID- 23169636
TI  - Combination of glycolysis inhibition with chemotherapy results in an antitumor
      immune response.
AB  - Most DNA-damaging agents are weak inducers of an anticancer immune response.
      Increased glycolysis is one of the best-described hallmarks of tumor cells;
      therefore, we investigated the impact of glycolysis inhibition, using 2
      deoxyglucose (2DG), in combination with cytotoxic agents on the induction of
      immunogenic cell death. We demonstrated that 2DG synergized with etoposide
      induced cytotoxicity and significantly increased the life span of immunocompetent
      mice but not immunodeficient mice. We then established that only cotreated cells
      induced an efficient tumor-specific T-cell activation ex vivo and that tumor
      antigen-specific T cells could only be isolated from cotreated animals. In
      addition, only when mice were immunized with cotreated dead tumor cells could
      they be protected (vaccinated) from a subsequent challenge using the same tumor
      in viable form. Finally, we demonstrated that this effect was at least partially
      mediated through ERp57/calreticulin exposure on the plasma membrane. These data
      identify that the targeting of glycolysis can convert conventional tolerogenic
      cancer cell death stimuli into immunogenic ones, thus creating new strategies for
      immunogenic chemotherapy.

PMID- 23169638
TI  - Biomimetic peptoid oligomers as dual-action antifreeze agents.
AB  - The ability of natural peptides and proteins to influence the formation of
      inorganic crystalline materials has prompted the design of synthetic compounds
      for the regulation of crystal growth, including the freezing of water and growth
      of ice crystals. Despite their versatility and ease of structural modification,
      peptidomimetic oligomers have not yet been explored extensively as
      crystallization modulators. This report describes a library of synthetic N
      substituted glycine peptoid oligomers that possess "dual-action" antifreeze
      activity as exemplified by ice crystal growth inhibition concomitant with melting
      temperature reduction. We investigated the structural features responsible for
      these phenomena and observed that peptoid antifreeze activities depend both on
      oligomer backbone structure and side chain chemical composition. These studies
      reveal the capability of peptoids to act as ice crystallization regulators,
      enabling the discovery of a unique and diverse family of synthetic oligomers with
      potential as antifreeze agents in food production and biomedicine.

PMID- 23169639
TI  - Improved herbivore resistance in cultivated tomato with the sesquiterpene
      biosynthetic pathway from a wild relative.
AB  - Tomato breeding has been tremendously efficient in increasing fruit quality and
      quantity but did not focus on improving herbivore resistance. The biosynthetic
      pathway for the production of 7-epizingiberene in a wild tomato was introduced
      into a cultivated greenhouse variety with the aim to obtain herbivore resistance.
      7-Epizingiberene is a specific sesquiterpene with toxic and repellent properties
      that is produced and stored in glandular trichomes. We identified 7
      epizingiberene synthase (ShZIS) that belongs to a new class of sesquiterpene
      synthases, exclusively using Z-Z-farnesyl-diphosphate (zFPP) in plastids,
      probably arisen through neo-functionalization of a common ancestor. Expression of
      the ShZIS and zFPP synthases in the glandular trichomes of cultivated tomato
      resulted in the production of 7-epizingiberene. These tomatoes gained resistance
      to several herbivores that are pests of tomato. Hence, introduction of this
      sesquiterpene biosynthetic pathway into cultivated tomatoes resulted in improved
      herbivore resistance.

PMID- 23169640
TI  - miR-155 targets histone deacetylase 4 (HDAC4) and impairs transcriptional
      activity of B-cell lymphoma 6 (BCL6) in the EMU-miR-155 transgenic mouse model.
AB  - Multiple studies have established that microRNAs (miRNAs) are involved in the
      initiation and progression of cancer. Notably, miR-155 is one of the most
      overexpressed miRNAs in several solid and hematological malignancies. Ectopic miR
      155 expression in mice B cells (EMU-miR-155 transgenic mice) has been shown to
      induce pre-B-cell proliferation followed by high-grade lymphoma/leukemia. Loss of
      miR-155 in mice resulted in impaired immunity due to defective T-cell-mediated
      immune response. Here we provide a mechanistic insight into miR-155-induced
      leukemogenesis in the EMU-miR-155 mouse model through genome-wide transcriptome
      analysis of naive B cells and target studies. We found that a key transcriptional
      repressor and proto-oncogene, Bcl6 is significantly down-regulated in EMU-miR-155
      mice. The reduction of Bcl6 subsequently leads to de-repression of some of the
      known Bcl6 targets like inhibitor of differentiation (Id2), interleukin-6 (IL6),
      cMyc, Cyclin D1, and Mip1alpha/ccl3, all of which promote cell survival and
      proliferation. We show that Bcl6 is indirectly regulated by miR-155 through
      Mxd1/Mad1 up-regulation. Interestingly, we found that miR-155 directly targets
      HDAC4, a corepressor partner of BCL6. Furthermore, ectopic expression of HDAC4 in
      human-activated B-cell-type diffuse large B-cell lymphoma (DLBCL) cells results
      in reduced miR-155-induced proliferation, clonogenic potential, and increased
      apoptosis. Meta-analysis of the diffuse large B-cell lymphoma patient microarray
      data showed that miR-155 expression is inversely correlated with Bcl6 and Hdac4.
      Hence this study provides a better understanding of how miR-155 causes disruption
      of the BCL6 transcriptional machinery that leads to up-regulation of the survival
      and proliferation genes in miR-155-induced leukemias.

PMID- 23169641
TI  - The dynamic pause-unpackaging state, an off-translocation recovery state of a DNA
      packaging motor from bacteriophage T4.
AB  - Tailed bacteriophages and herpes viruses use powerful ATP-driven molecular motors
      to translocate their viral genomes into a preformed capsid shell. The
      bacteriophage T4 motor, a pentamer of the large terminase protein (gp17)
      assembled at the portal vertex of the prohead, is the fastest and most powerful
      known, consistent with the need to package a ~170-kb viral genome in
      approximately 5 min. Although much is known about the mechanism of DNA
      translocation, very little is known about how ATP modulates motor-DNA
      interactions. Here, we report single-molecule measurements of the phage T4 gp17
      motor by using dual-trap optical tweezers under different conditions of
      perturbation. Unexpectedly, the motor pauses randomly when ATP is limiting, for
      an average of 1 s, and then resumes translocation. During pausing, DNA is
      unpackaged, a phenomenon so far observed only in T4, where some of the packaged
      DNA is slowly released. We propose that the motor pauses whenever it encounters a
      subunit in the apo state with the DNA bound weakly and incorrectly. Pausing
      allows the subunit to capture ATP, whereas unpackaging allows scanning of DNA
      until a correct registry is established. Thus, the "pause-unpackaging" state is
      an off-translocation recovery state wherein the motor, sometimes by taking a few
      steps backward, can bypass the impediments encountered along the translocation
      path. These results lead to a four-state mechanochemical model that provides
      insights into the mechanisms of translocation of an intricately branched
      concatemeric viral genome.

PMID- 23169642
TI  - Dual-acting riboswitch control of translation initiation and mRNA decay.
AB  - Riboswitches are mRNA regulatory elements that control gene expression by
      altering their structure in response to specific metabolite binding. In bacteria,
      riboswitches consist of an aptamer that performs ligand recognition and an
      expression platform that regulates either transcription termination or
      translation initiation. Here, we describe a dual-acting riboswitch from
      Escherichia coli that, in addition to modulating translation initiation, also is
      directly involved in the control of initial mRNA decay. Upon lysine binding, the
      lysC riboswitch adopts a conformation that not only inhibits translation
      initiation but also exposes RNase E cleavage sites located in the riboswitch
      expression platform. However, in the absence of lysine, the riboswitch folds into
      an alternative conformation that simultaneously allows translation initiation and
      sequesters RNase E cleavage sites. Both regulatory activities can be individually
      inhibited, indicating that translation initiation and mRNA decay can be modulated
      independently using the same conformational switch. Because RNase E cleavage
      sites are located in the riboswitch sequence, this riboswitch provides a unique
      means for the riboswitch to modulate RNase E cleavage activity directly as a
      function of lysine. This dual inhibition is in contrast to other riboswitches,
      such as the thiamin pyrophosphate-sensing thiM riboswitch, which triggers mRNA
      decay only as a consequence of translation inhibition. The riboswitch control of
      RNase E cleavage activity is an example of a mechanism by which metabolite
      sensing is used to regulate gene expression of single genes or even large
      polycistronic mRNAs as a function of environmental changes.

PMID- 23169643
TI  - pH-triggered, activated-state conformations of the influenza hemagglutinin fusion
      peptide revealed by NMR.
AB  - The highly conserved first 23 residues of the influenza hemagglutinin HA2 subunit
      constitute the fusion domain, which plays a pivotal role in fusing viral and host
      cell membranes. At neutral pH, this peptide adopts a tight helical hairpin wedge
      structure, stabilized by aliphatic hydrogen bonding and charge-dipole
      interactions. We demonstrate that at low pH, where the fusion process is
      triggered, the native peptide transiently visits activated states that are very
      similar to those sampled by a G8A mutant. This mutant retains a small fraction of
      helical hairpin conformation, in rapid equilibrium with at least two open
      structures. The exchange rate between the closed and open conformations of the
      wild-type fusion peptide is ~40 kHz, with a total open-state population of ~20%.
      Transitions to these activated states are likely to play a crucial role in
      formation of the fusion pore, an essential structure required in the final stage
      of membrane fusion.

PMID- 23169644
TI  - Chemogenomic approach identified yeast YLR143W as diphthamide synthetase.
AB  - Many genes are of unknown functions in any sequenced genome. A combination of
      chemical and genetic perturbations has been used to investigate gene functions.
      Here we present a case that such "chemogenomics" information can be effectively
      used to identify missing genes in a defined biological pathway. In particular, we
      identified the previously unknown enzyme diphthamide synthetase for the last step
      of diphthamide biosynthesis. We found that yeast protein YLR143W is the
      diphthamide synthetase catalyzing the last amidation step using ammonium and ATP.
      Diphthamide synthetase is evolutionarily conserved in eukaryotes. The previously
      uncharacterized human gene ATPBD4 is the ortholog of yeast YLR143W and fully
      rescues the deletion of YLR143W in yeast.

PMID- 23169645
TI  - Cryo-EM structure of a 3D DNA-origami object.
AB  - A key goal for nanotechnology is to design synthetic objects that may ultimately
      achieve functionalities known today only from natural macromolecular complexes.
      Molecular self-assembly with DNA has shown potential for creating user-defined 3D
      scaffolds, but the level of attainable positional accuracy has been unclear. Here
      we report the cryo-EM structure and a full pseudoatomic model of a discrete DNA
      object that is almost twice the size of a prokaryotic ribosome. The structure
      provides a variety of stable, previously undescribed DNA topologies for future
      use in nanotechnology and experimental evidence that discrete 3D DNA scaffolds
      allow the positioning of user-defined structural motifs with an accuracy that is
      similar to that observed in natural macromolecules. Thereby, our results indicate
      an attractive route to fabricate nanoscale devices that achieve complex
      functionalities by DNA-templated design steered by structural feedback.

PMID- 23169646
TI  - Mapping Greenland's mass loss in space and time.
AB  - The melting of polar ice sheets is a major contributor to global sea-level rise.
      Early estimates of the mass lost from the Greenland ice cap, based on satellite
      gravity data collected by the Gravity Recovery and Climate Experiment, have
      widely varied. Although the continentally and decadally averaged estimated trends
      have now more or less converged, to this date, there has been little clarity on
      the detailed spatial distribution of Greenland's mass loss and how the
      geographical pattern has varied on relatively shorter time scales. Here, we
      present a spatially and temporally resolved estimation of the ice mass change
      over Greenland between April of 2002 and August of 2011. Although the total mass
      loss trend has remained linear, actively changing areas of mass loss were
      concentrated on the southeastern and northwestern coasts, with ice mass in the
      center of Greenland steadily increasing over the decade.

PMID- 23169647
TI  - Nezha/CAMSAP3 and CAMSAP2 cooperate in epithelial-specific organization of
      noncentrosomal microtubules.
AB  - Major microtubules in epithelial cells are not anchored to the centrosome, in
      contrast to the centrosomal radiation of microtubules in other cell types. It
      remains to be discovered how these epithelial microtubules are generated and
      stabilized at noncentrosomal sites. Here, we found that Nezha [also known as
      calmodulin-regulated spectrin-associated protein 3 (CAMSAP3)] and its related
      protein, CAMSAP2, cooperate in organization of noncentrosomal microtubules. These
      two CAMSAP molecules coclustered at the minus ends of noncentrosomal microtubules
      and thereby stabilized them. Depletion of CAMSAPs caused a marked reduction of
      microtubules with polymerizing plus ends, concomitantly inducing the growth of
      microtubules from the centrosome. In CAMSAP-depleted cells, early endosomes and
      the Golgi apparatus exhibited irregular distributions. These effects of CAMSAP
      depletion were maximized when both CAMSAPs were removed. These findings suggest
      that CAMSAP2 and -3 work together to maintain noncentrosomal microtubules,
      suppressing the microtubule-organizing ability of the centrosome, and that the
      network of CAMSAP-anchored microtubules is important for proper organelle
      assembly.

PMID- 23169649
TI  - Profile of Roberta L. Rudnick.

PMID- 23169648
TI  - TRIM28 mediates chromatin modifications at the TCRalpha enhancer and regulates
      the development of T and natural killer T cells.
AB  - T-cell receptor-alpha (TCRalpha) rearrangement in CD4(+)CD8(+) double-positive
      immature thymocytes is a prerequisite for production of alphabeta T cells and
      invariant natural killer T cells. This developmental event is regulated by the
      TCRalpha enhancer (Ealpha), which induces chromatin modification and recruitment
      of the recombination-activating proteins Rag1 and Rag2. However, the molecular
      mechanism underlying the activation and long-range action of Ealpha remains
      incompletely understood. We show here that the chromatin-modifying factor TRIM28
      is highly expressed in double-positive thymocytes and persistently phosphorylated
      at serine 473. TRIM28 binds to Ealpha and induces histone 3 lysine 4
      trimethylation in the Ealpha and distant regions of the TCRalpha locus, coupled
      with recruitment of Rag proteins. T-cell-conditional ablation of TRIM28 impaired
      TCRalpha gene rearrangement and compromised the development of alphabeta T cells
      and invariant natural killer T cells. These findings establish TRIM28 as a unique
      regulator of thymocyte development and highlight an epigenetic mechanism
      involving TRIM28-mediated active chromatin modification in the TCRalpha locus.

PMID- 23169650
TI  - Controlling interactions in supported bilayers from weak electrostatic repulsion
      to high osmotic pressure.
AB  - Understanding interactions between membranes requires measurements on well
      controlled systems close to natural conditions, in which fluctuations play an
      important role. We have determined, by grazing incidence X-ray scattering, the
      interaction potential between two lipid bilayers, one adsorbed on a solid surface
      and the other floating close by. We find that interactions in this highly
      hydrated model system are two orders of magnitude softer than in previously
      reported work on multilayer stacks. This is attributed to the weak electrostatic
      repulsion due to the small fraction of ionized lipids in supported bilayers with
      a lower number of defects. Our data are consistent with the Poisson-Boltzmann
      theory, in the regime where repulsion is dominated by the entropy of counter
      ions. We also have unique access to very weak entropic repulsion potentials,
      which allowed us to discriminate between the various models proposed in the
      literature. We further demonstrate that the interaction potential between
      supported bilayers can be tuned at will by applying osmotic pressure, providing a
      way to manipulate these model membranes, thus considerably enlarging the range of
      biological or physical problems that can be addressed.

PMID- 23169651
TI  - DNA damage checkpoint triggers autophagy to regulate the initiation of anaphase.
AB  - Budding yeast cells suffering a single unrepaired double-strand break (DSB)
      trigger the Mec1 (ATR)-dependent DNA damage response that causes them to arrest
      before anaphase for 12-15 h. Here we find that hyperactivation of the cytoplasm
      to-vacuole (CVT) autophagy pathway causes the permanent G2/M arrest of cells with
      a single DSB that is reflected in the nuclear exclusion of both Esp1 and Pds1.
      Transient relocalization of Pds1 is also seen in wild-type cells lacking vacuolar
      protease activity after induction of a DSB. Arrest persists even as the DNA
      damage-dependent phosphorylation of Rad53 diminishes. Permanent arrest can be
      overcome by blocking autophagy, by deleting the vacuolar protease Prb1, or by
      driving Esp1 into the nucleus with a SV40 nuclear localization signal. Autophagy
      in response to DNA damage can be induced in three different ways: by deleting the
      Golgi-associated retrograde protein complex (GARP), by adding rapamycin, or by
      overexpression of a dominant ATG13-8SA mutation.

PMID- 23169652
TI  - The Miocene mammal Necrolestes demonstrates the survival of a Mesozoic nontherian
      lineage into the late Cenozoic of South America.
AB  - The early Miocene mammal Necrolestes patagonensis from Patagonia, Argentina, was
      described in 1891 as the only known extinct placental "insectivore" from South
      America (SA). Since then, and despite the discovery of additional well-preserved
      material, the systematic status of Necrolestes has remained in flux, with earlier
      studies leaning toward placental affinities and more recent ones endorsing either
      therian or specifically metatherian relationships. We have further prepared the
      best-preserved specimens of Necrolestes and compared them with newly discovered
      nontribosphenic Mesozoic mammals from Argentina; based on this, we conclude that
      Necrolestes is related neither to marsupials nor placentals but is a late
      surviving member of the recently recognized nontherian clade Meridiolestida,
      which is currently known only from SA. This conclusion is supported by a
      morphological phylogenetic analysis that includes a broad sampling of therian and
      nontherian taxa and that places Necrolestes within Meridiolestida. Thus,
      Necrolestes is a remnant of the highly endemic Mesozoic fauna of nontribosphenic
      mammals in SA and extends the known record of meridiolestidans by almost 45
      million years. Together with other likely relictual mammals from earlier in the
      Cenozoic of SA and Antarctica, Necrolestes demonstrates the ecological diversity
      of mammals and the mosaic pattern of fauna replacement in SA during the Cenozoic.
      In contrast to northern continents, the Cenozoic faunal history of SA was
      characterized by a long period of interaction between endemic mammalian lineages
      of Mesozoic origin and metatherian and eutherian lineages that probably dispersed
      to SA during the latest Cretaceous or earliest Paleocene.

PMID- 23169653
TI  - Conditionally reprogrammed cells represent a stem-like state of adult epithelial
      cells.
AB  - The combination of irradiated fibroblast feeder cells and Rho kinase inhibitor, Y
      27632, conditionally induces an indefinite proliferative state in primary
      mammalian epithelial cells. These conditionally reprogrammed cells (CRCs) are
      karyotype-stable and nontumorigenic. Because self-renewal is a recognized
      property of stem cells, we investigated whether Y-27632 and feeder cells induced
      a stem-like phenotype. We found that CRCs share characteristics of adult stem
      cells and exhibit up-regulated expression of alpha6 and beta1 integrins,
      DeltaNp63alpha, CD44, and telomerase reverse transcriptase, as well as decreased
      Notch signaling and an increased level of nuclear beta-catenin. The induction of
      CRCs is rapid (occurs within 2 d) and results from reprogramming of the entire
      cell population rather than the selection of a minor subpopulation. CRCs do not
      overexpress the transcription factor sets characteristic of embryonic or induced
      pluripotent stem cells (e.g., Sox2, Oct4, Nanog, or Klf4). The induction of CRCs
      is also reversible, and removal of Y-27632 and feeders allows the cells to
      differentiate normally. Thus, when CRCs from ectocervical epithelium or tracheal
      epithelium are placed in an air-liquid interface culture system, the cervical
      cells form a well differentiated stratified squamous epithelium, whereas the
      tracheal cells form a ciliated airway epithelium. We discuss the diagnostic and
      therapeutic opportunities afforded by a method that can generate adult stem-like
      cells in vitro without genetic manipulation.

PMID- 23169654
TI  - GIRK channel modulation by assembly with allosterically regulated RGS proteins.
AB  - G-protein-activated inward-rectifying K(+) (GIRK) channels hyperpolarize neurons
      to inhibit synaptic transmission throughout the nervous system. By accelerating G
      protein deactivation kinetics, the regulator of G-protein signaling (RGS) protein
      family modulates the timing of GIRK activity. Despite many investigations,
      whether RGS proteins modulate GIRK activity in neurons by mechanisms involving
      kinetic coupling, collision coupling, or macromolecular complex formation has
      remained unknown. Here we show that GIRK modulation occurs by channel assembly
      with R7-RGS/Gbeta5 complexes under allosteric control of R7 RGS-binding protein
      (R7BP). Elimination of R7BP occludes the Gbeta5 subunit that interacts with GIRK
      channels. R7BP-bound R7-RGS/Gbeta5 complexes and Gbetagamma dimers interact
      noncompetitively with the intracellular domain of GIRK channels to facilitate
      rapid activation and deactivation of GIRK currents. By disrupting this
      allosterically regulated assembly mechanism, R7BP ablation augments GIRK
      activity. This enhanced GIRK activity increases the drug effects of agonists
      acting at G-protein-coupled receptors that signal via GIRK channels, as indicated
      by greater antinociceptive effects of GABA(B) or MU-opioid receptor agonists.
      These findings show that GIRK current modulation in vivo requires channel
      assembly with allosterically regulated RGS protein complexes, which provide a
      target for modulating GIRK activity in neurological disorders in which these
      channels have crucial roles, including pain, epilepsy, Parkinson's disease and
      Down syndrome.

PMID- 23169655
TI  - Inhibition of glutamate carboxypeptidase II (GCPII) activity as a treatment for
      cognitive impairment in multiple sclerosis.
AB  - Half of all patients with multiple sclerosis (MS) experience cognitive
      impairment, for which there is no pharmacological treatment. Using magnetic
      resonance spectroscopy (MRS), we examined metabolic changes in the hippocampi of
      MS patients, compared the findings to performance on a neurocognitive test
      battery, and found that N-acetylaspartylglutamate (NAAG) concentration correlated
      with cognitive functioning. Specifically, MS patients with cognitive impairment
      had low hippocampal NAAG levels, whereas those with normal cognition demonstrated
      higher levels. We then evaluated glutamate carboxypeptidase II (GCPII)
      inhibitors, known to increase brain NAAG levels, on cognition in the experimental
      autoimmune encephalomyelitis (EAE) model of MS. Whereas GCPII inhibitor
      administration did not affect physical disabilities, it increased brain NAAG
      levels and dramatically improved learning and memory test performance compared
      with vehicle-treated EAE mice. These data suggest that NAAG is a unique biomarker
      for cognitive function in MS and that inhibition of GCPII might be a unique
      therapeutic strategy for recovery of cognitive function.

PMID- 23169656
TI  - Cardiac myosin binding protein-C restricts intrafilament torsional dynamics of
      actin in a phosphorylation-dependent manner.
AB  - We have determined the effects of myosin binding protein-C (MyBP-C) and its
      domains on the microsecond rotational dynamics of actin, detected by time
      resolved phosphorescence anisotropy (TPA). MyBP-C is a multidomain modulator of
      striated muscle contraction, interacting with myosin, titin, and possibly actin.
      Cardiac and slow skeletal MyBP-C are known substrates for protein kinase-A (PKA),
      and phosphorylation of the cardiac isoform alters contractile properties and
      myofilament structure. To determine the effects of MyBP-C on actin structural
      dynamics, we labeled actin at C374 with a phosphorescent dye and performed TPA
      experiments. The interaction of all three MyBP-C isoforms with actin increased
      the final anisotropy of the TPA decay, indicating restriction of the amplitude of
      actin torsional flexibility by 15-20 degrees  at saturation of the TPA effect.
      PKA phosphorylation of slow skeletal and cardiac MyBP-C relieved the restriction
      of torsional amplitude but also decreased the rate of torsional motion. In the
      case of fast skeletal MyBP-C, its effect on actin dynamics was unchanged by
      phosphorylation. The isolated C-terminal half of cardiac MyBP-C (C5-C10) had
      effects similar to those of the full-length protein, and it bound actin more
      tightly than the N-terminal half (C0-C4), which had smaller effects on actin
      dynamics that were independent of PKA phosphorylation. We propose that these MyBP
      C-induced changes in actin dynamics play a role in the functional effects of MyBP
      C on the actin-myosin interaction.

PMID- 23169657
TI  - Connexin45 modulates the proliferation of transit-amplifying precursor cells in
      the mouse subventricular zone.
AB  - Connexins have been implicated in the regulation of precursor cell migration and
      proliferation during embryonic development of the mammalian brain. However, their
      function in postnatal neurogenesis is unclear. Here we demonstrate that connexin
      (Cx) 45 is expressed in transit-amplifying cells and neuroblasts in the postnatal
      subventricular zone (SVZ) and modulated the proliferation of SVZ-derived
      precursor cells in vivo. Thus, overexpression of Cx45 by retroviral injections
      increased the proliferation of Mash-1-positive transit-amplifying precursor cells
      in the SVZ. Conversely, conditional deletion of Cx45 in precursor cells decreased
      proliferation. Finally, we established that Cx45 positively influences cell cycle
      reentry via ATP signaling that involves intracellular calcium stores and ERK1/2
      signaling.

PMID- 23169658
TI  - MYBL2 is a substrate of GSK3-like kinase BIN2 and acts as a corepressor of BES1
      in brassinosteroid signaling pathway in Arabidopsis.
AB  - Plant steroid hormones, brassinosteroids (BRs), play important roles in plants.
      BRs regulate the expression of several thousand genes, half of which are induced
      and the other half repressed by the hormone. BRs signal through plasma membrane
      localized receptor kinase brassinosteroid-insensitive 1 (BRI1), BRI1-associated
      receptor kinase (BAK1), and several intermediates to regulate the protein levels,
      cellular localizations, and/or DNA binding of BRI1-EMS suppressor 1
      (BES1)/brassinazole-resistant 1 (BZR1) family transcription factors. Although
      BES1 is known to interact with other transcription factors, histone-modifying
      enzymes, and transcription elongation factors to activate BR-induced genes, how
      BES1 mediates the BR-repressed gene expression is not known. Here, we show that
      BES1 interacts with myeloblastosis family transcription factor-like 2 (MYBL2), a
      transcription repressor, to down-regulate BR-repressed gene expression. The loss
      of-function mybl2 mutant enhances the phenotype of a weak allele of bri1 and
      suppresses the constitutive BR-response phenotype of bes1-D. The results suggest
      that suppression of BR-repressed gene expression is required for optimal BR
      response. Moreover, MYBL2 is a substrate of glycogen synthase kinase 3 (GSK3)
      like kinase brassinosteroid-insensitive 2 (BIN2), which has been well established
      as a negative regulator in the BR pathway by phosphorylating and inhibiting the
      functions of BES1/BZR1. Unlike BIN2 phosphorylation of BES1/BZR1 leading to
      protein degradation, BIN2 phosphorylation stabilizes MYBL2. Such dual role of
      phosphorylation has also been reported in WNT signaling pathway in which GSK3
      phosphorylation destabilizes beta-catenin and stabilizes Axin, a scaffolding
      protein facilitating the phosphorylation of beta-catenin by GSK3. Our results
      thus establish the mechanisms for BR-repressed gene expression and the
      integration of BR signaling and BR transcriptional network.

PMID- 23169659
TI  - Mechanism for adaptive remodeling of the bacterial flagellar switch.
AB  - The bacterial flagellar motor has been shown in previous work to adapt to changes
      in the steady-state concentration of the chemotaxis signaling molecule, CheY-P,
      by changing the FliM content. We show here that the number of FliM molecules in
      the motor and the fraction of FliM molecules that exchange depend on the
      direction of flagellar rotation, not on CheY-P binding per se. Our results are
      consistent with a model in which the structural differences associated with the
      direction of rotation modulate the strength of FliM binding. When the motor spins
      counterclockwise, FliM binding strengthens, the fraction of FliM molecules that
      exchanges decreases, and the ring content increases. The larger number of CheY-P
      binding sites enhances the motor's sensitivity, i.e., the motor adapts. An
      interesting unresolved question is how additional copies of FliM might be
      accommodated.

PMID- 23169661
TI  - Directional grain growth from anisotropic kinetic roughening of grain boundaries
      in sheared colloidal crystals.
AB  - The fabrication of functional materials via grain growth engineering implicitly
      relies on altering the mobilities of grain boundaries (GBs) by applying external
      fields. Although computer simulations have alluded to kinetic roughening as a
      potential mechanism for modifying GB mobilities, its implications for grain
      growth have remained largely unexplored owing to difficulties in bridging the
      widely separated length and time scales. Here, by imaging GB particle dynamics as
      well as grain network evolution under shear, we present direct evidence for
      kinetic roughening of GBs and unravel its connection to grain growth in driven
      colloidal polycrystals. The capillary fluctuation method allows us to
      quantitatively extract shear-dependent effective mobilities. Remarkably, our
      experiments reveal that for sufficiently large strains, GBs with normals parallel
      to shear undergo preferential kinetic roughening, resulting in anisotropic
      enhancement of effective mobilities and hence directional grain growth. Single
      particle level analysis shows that the mobility anisotropy emerges from strain
      induced directional enhancement of activated particle hops normal to the GB
      plane. We expect our results to influence materials fabrication strategies for
      atomic and block copolymeric polycrystals as well.

PMID- 23169660
TI  - Palette of fluorinated voltage-sensitive hemicyanine dyes.
AB  - Optical recording of membrane potential permits spatially resolved measurement of
      electrical activity in subcellular regions of single cells, which would be
      inaccessible to electrodes, and imaging of spatiotemporal patterns of action
      potential propagation in excitable tissues, such as the brain or heart. However,
      the available voltage-sensitive dyes (VSDs) are not always spectrally compatible
      with newly available optical technologies for sensing or manipulating the
      physiological state of a system. Here, we describe a series of 19 fluorinated
      VSDs based on the hemicyanine class of chromophores. Strategic placement of the
      fluorine atoms on the chromophores can result in either blue or red shifts in the
      absorbance and emission spectra. The range of one-photon excitation wavelengths
      afforded by these new VSDs spans 440-670 nm; the two-photon excitation range is
      900-1,340 nm. The emission of each VSD is shifted by at least 100 nm to the red
      of its one-photon excitation spectrum. The set of VSDs, thus, affords an extended
      toolkit for optical recording to match a broad range of experimental
      requirements. We show the sensitivity to voltage and the photostability of the
      new VSDs in a series of experimental preparations ranging in scale from single
      dendritic spines to whole heart. Among the advances shown in these applications
      are simultaneous recording of voltage and calcium in single dendritic spines and
      optical electrophysiology recordings using two-photon excitation above 1,100 nm.

PMID- 23169663
TI  - Calaxin drives sperm chemotaxis by Ca2+-mediated direct modulation of a dynein
      motor.
AB  - Sperm chemotaxis occurs widely in animals and plants and plays an important role
      in the success of fertilization. Several studies have recently demonstrated that
      Ca(2+) influx through specific Ca(2+) channels is a prerequisite for sperm
      chemotactic movement. However, the regulator that modulates flagellar movement in
      response to Ca(2+) is unknown. Here we show that a neuronal calcium sensor,
      calaxin, directly acts on outer-arm dynein and regulates specific flagellar
      movement during sperm chemotaxis. Calaxin inhibition resulted in significant loss
      of sperm chemotactic movement, despite normal increases in intracellular calcium
      concentration. Using a demembranated sperm model, we demonstrate that calaxin is
      essential for generation and propagation of Ca(2+)-induced asymmetric flagellar
      bending. An in vitro motility assay revealed that calaxin directly suppressed the
      velocity of microtubule sliding by outer-arm dynein at high Ca(2+)
      concentrations. This study describes the missing link between chemoattractant
      mediated Ca(2+) signaling and motor-driven microtubule sliding during sperm
      chemotaxis.

PMID- 23169664
TI  - Identification of nonferritin mitochondrial iron deposits in a mouse model of
      Friedreich ataxia.
AB  - There is no effective treatment for the cardiomyopathy of the most common
      autosomal recessive ataxia, Friedreich ataxia (FA). This disease is due to
      decreased expression of the mitochondrial protein, frataxin, which leads to
      alterations in mitochondrial iron (Fe) metabolism. The identification of
      potentially toxic mitochondrial Fe deposits in FA suggests Fe plays a role in its
      pathogenesis. Studies using the muscle creatine kinase (MCK) conditional frataxin
      knockout mouse that mirrors the disease have demonstrated frataxin deletion
      alters cardiac Fe metabolism. Indeed, there are pronounced changes in Fe
      trafficking away from the cytosol to the mitochondrion, leading to a cytosolic Fe
      deficiency. Considering Fe deficiency can induce apoptosis and cell death, we
      examined the effect of dietary Fe supplementation, which led to body Fe loading
      and limited the cardiac hypertrophy in MCK mutants. Furthermore, this study
      indicates a unique effect of heart and skeletal muscle-specific frataxin deletion
      on systemic Fe metabolism. Namely, frataxin deletion induces a signaling
      mechanism to increase systemic Fe levels and Fe loading in tissues where frataxin
      expression is intact (i.e., liver, kidney, and spleen). Examining the mutant
      heart, native size-exclusion chromatography, transmission electron microscopy,
      Mossbauer spectroscopy, and magnetic susceptibility measurements demonstrated
      that in the absence of frataxin, mitochondria contained biomineral Fe aggregates,
      which were distinctly different from isolated mammalian ferritin molecules. These
      mitochondrial aggregates of Fe, phosphorus, and sulfur, probably contribute to
      the oxidative stress and pathology observed in the absence of frataxin.

PMID- 23169665
TI  - Mutual protection of ribosomal proteins L5 and L11 from degradation is essential
      for p53 activation upon ribosomal biogenesis stress.
AB  - Impairment of ribosomal biogenesis can activate the p53 protein independently of
      DNA damage. The ability of ribosomal proteins L5, L11, L23, L26, or S7 to bind
      Mdm2 and inhibit its ubiquitin ligase activity has been suggested as a critical
      step in p53 activation under these conditions. Here, we report that L5 and L11
      are particularly important for this response. Whereas several other newly
      synthesized ribosomal proteins are degraded by proteasomes upon inhibition of Pol
      I activity by actinomycin D, L5 and L11 accumulate in the ribosome-free fraction
      where they bind to Mdm2. This selective accumulation of free L5 and L11 is due to
      their mutual protection from proteasomal degradation. Furthermore, the
      endogenous, newly synthesized L5 and L11 continue to be imported into nucleoli
      even after nucleolar disruption and colocalize with Mdm2, p53, and promyelocytic
      leukemia protein. This suggests that the disrupted nucleoli may provide a
      platform for L5- and L11-dependent p53 activation, implying a role for the
      nucleolus in p53 activation by ribosomal biogenesis stress. These findings may
      have important implications with respect to understanding the pathogenesis of
      diseases caused by impaired ribosome biogenesis.

PMID- 23169668
TI  - Optogenetically induced sleep spindle rhythms alter sleep architectures in mice.
AB  - Sleep spindles are rhythmic patterns of neuronal activity generated within the
      thalamocortical circuit. Although spindles have been hypothesized to protect
      sleep by reducing the influence of external stimuli, it remains to be confirmed
      experimentally whether there is a direct relationship between sleep spindles and
      the stability of sleep. We have addressed this issue by using in vivo
      photostimulation of the thalamic reticular nucleus of mice to generate spindle
      oscillations that are structurally and functionally similar to spontaneous sleep
      spindles. Such optogenetic generation of sleep spindles increased the duration of
      non-rapid eye movement (NREM) sleep. Furthermore, the density of sleep spindles
      was correlated with the amount of NREM sleep. These findings establish a causal
      relationship between sleep spindles and the stability of NREM sleep, strongly
      supporting a role for the thalamocortical circuit in sleep regulation.

PMID- 23169667
TI  - Heptahelical protein PQLC2 is a lysosomal cationic amino acid exporter underlying
      the action of cysteamine in cystinosis therapy.
AB  - Cystinosin, the lysosomal cystine exporter defective in cystinosis, is the
      founding member of a family of heptahelical membrane proteins related to
      bacteriorhodopsin and characterized by a duplicated motif termed the PQ loop. PQ
      loop proteins are more frequent in eukaryotes than in prokaryotes; except for
      cystinosin, their molecular function remains elusive. In this study, we report
      that three yeast PQ-loop proteins of unknown function, Ypq1, Ypq2, and Ypq3,
      localize to the vacuolar membrane and are involved in homeostasis of cationic
      amino acids (CAAs). We also show that PQLC2, a mammalian PQ-loop protein closely
      related to yeast Ypq proteins, localizes to lysosomes and catalyzes a robust,
      electrogenic transport that is selective for CAAs and strongly activated at low
      extracytosolic pH. Heterologous expression of PQLC2 at the yeast vacuole rescues
      the resistance phenotype of an ypq2 mutant to canavanine, a toxic analog of
      arginine efficiently transported by PQLC2. Finally, PQLC2 transports a lysine
      like mixed disulfide that serves as a chemical intermediate in cysteamine therapy
      of cystinosis, and PQLC2 gene silencing trapped this intermediate in cystinotic
      cells. We conclude that PQLC2 and Ypq1-3 proteins are lysosomal/vacuolar
      exporters of CAAs and suggest that small-molecule transport is a conserved
      feature of the PQ-loop protein family, in agreement with its distant similarity
      to SWEET sugar transporters and to the mitochondrial pyruvate carrier. The
      elucidation of PQLC2 function may help improve cysteamine therapy. It may also
      clarify the origin of CAA abnormalities in Batten disease.

PMID- 23169669
TI  - Low-affinity B cells transport viral particles from the lung to the spleen to
      initiate antibody responses.
AB  - The lung is an important entry site for pathogens; its exposure to antigens
      results in systemic as well as local IgA and IgG antibodies. Here we show that
      intranasal administration of virus-like particles (VLPs) results in splenic B
      cell responses with strong local germinal-center formation. Surprisingly, VLPs
      were not transported from the lung to the spleen in a free form but by B cells.
      The interaction between VLPs and B cells was initiated in the lung and occurred
      independently of complement receptor 2 and Fcgamma receptors, but was dependent
      upon B-cell receptors. Thus, B cells passing through the lungs bind VLPs via
      their B-cell receptors and deliver them to local B cells within the splenic B
      cell follicle. This process is fundamentally different from delivery of blood or
      lymph borne particulate antigens, which are transported into B cell follicles by
      binding to complement receptors on B cells.

PMID- 23169672
TI  - Tead4 is constitutively nuclear, while nuclear vs. cytoplasmic Yap distribution
      is regulated in preimplantation mouse embryos.

PMID- 23169671
TI  - In vivo directed differentiation of pluripotent stem cells for skeletal
      regeneration.
AB  - Pluripotent cells represent a powerful tool for tissue regeneration, but their
      clinical utility is limited by their propensity to form teratomas. Little is
      known about their interaction with the surrounding niche following implantation
      and how this may be applied to promote survival and functional engraftment. In
      this study, we evaluated the ability of an osteogenic microniche consisting of a
      hydroxyapatite-coated, bone morphogenetic protein-2-releasing poly-L-lactic acid
      scaffold placed within the context of a macroenvironmental skeletal defect to
      guide in vivo differentiation of both embryonic and induced pluripotent stem
      cells. In this setting, we found de novo bone formation and participation by
      implanted cells in skeletal regeneration without the formation of a teratoma.
      This finding suggests that local cues from both the implanted scaffold/cell micro
      and surrounding macroniche may act in concert to promote cellular survival and
      the in vivo acquisition of a terminal cell fate, thereby allowing for functional
      engraftment of pluripotent cells into regenerating tissue.

PMID- 23169674
TI  - Central coherence in full recovery of anorexia nervosa.
AB  - OBJECTIVE: This study examined central coherence as a possible endophenotype in a
      large sample of women recovered from anorexia nervosa (rec AN). Recovery was
      defined by considering physiological, behavioural and psychological variables.
      METHOD: A total of 100 rec AN women and 100 healthy women completed the Rey
      Complex Figure Test, a measure for visual-spatial central coherence. The
      participants were matched 1:1 for age and educational level. RESULTS: Compared
      with the healthy control group, the rec AN group showed better accuracy in the
      copy condition. There was a trend for a local strategy in the rec AN group
      compared with a global strategy in the healthy control group. CONCLUSIONS: This
      sample of rec AN women showed no inefficiencies in global processing but a
      superior local processing after full recovery from AN.

PMID- 23169673
TI  - Choreoathetosis, congenital hypothyroidism and neonatal respiratory distress
      syndrome with intact NKX2-1.
AB  - Mutations in the NK2 homeobox 1 gene (NKX2-1) cause a rare syndrome known as
      choreoathetosis, congenital hypothyroidism, and neonatal respiratory distress
      syndrome (OMIM 610978). Here we present the first reported patient with this
      condition caused by a 14q13.3 deletion which is adjacent to but does not
      interrupt NKX2-1, and review the literature on this condition. The infant
      presented at 23 months with a history of developmental delay, hyperkinesia,
      recurrent respiratory infections, neonatal respiratory distress, and
      hypothyroidism. Choreiform movements and delayed motor milestones were first
      noted at 6-8 months of age. TSH levels had been consistently elevated from 8
      months of age. The clinical presentation was suggestive of an NKX2-1 mutation.
      Sequencing of all exons and splice site junctions of NKX2-1 was performed but was
      normal. Array CGH was then performed and a 3.29 Mb interstitial deletion at
      14q13.1-q13.3 was detected. The distal region of loss of the deletion disrupted
      the surfactant associated 3 (SFTA3) gene but did disrupt NKX2-1. Findings were
      confirmed on high resolution SNP array and multiplex semiquanitative PCR. NKX2-1
      encodes transcriptional factors involved in the developmental pathways for
      thyroid, lung, and brain. We hypothesize that the region centromeric to NKX2-1 is
      important for the normal functioning of this gene and when interrupted produces a
      phenotype that is typical of the choreoathetosis, congenital hypothyroidism, and
      neonatal respiratory distress syndrome, as seen in our patient. We conclude that
      deletions at 14q13.3 adjacent to but not involving NKX2-1 can cause
      choreoathetosis, congenital hypothyroidism, and neonatal respiratory distress
      syndrome.

PMID- 23169675
TI  - Totally organic biphasic solvent systems for extraction and descriptor
      determinations.
AB  - Partition between two immiscible solvents is widely used in sample preparation
      procedures for matrix simplification and isolation of target analytes, for
      separations using countercurrent, centrifugal partition, and liquid-liquid
      chromatography, and as a method for determining descriptors for use in modeling
      chemical, biological, and environmental processes. Until recently, most
      applications employed water as one component of the biphasic system. For
      compounds of low water solubility or stability, a series of totally organic
      biphasic systems have been developed to enhance the application range of liquid
      liquid partition methods. These systems, their characterization using the
      solvation parameter model, and applications to sample preparation and the
      determination of descriptors are described in this review.

PMID- 23169676
TI  - The roles of vitamin D in skeletal muscle: form, function, and metabolism.
AB  - Beyond its established role in bone and mineral homeostasis, there is emerging
      evidence that vitamin D exerts a range of effects in skeletal muscle. Reports of
      profound muscle weakness and changes in the muscle morphology of adults with
      vitamin D deficiency have long been described. These reports have been
      supplemented by numerous trials assessing the impact of vitamin D on muscle
      strength and mass and falls in predominantly elderly and deficient populations.
      At a basic level, animal models have confirmed that vitamin D deficiency and
      congenital aberrations in the vitamin D endocrine system may result in muscle
      weakness. To explain these effects, some molecular mechanisms by which vitamin D
      impacts on muscle cell differentiation, intracellular calcium handling, and
      genomic activity have been elucidated. There are also suggestions that vitamin D
      alters muscle metabolism, specifically its sensitivity to insulin, which is a
      pertinent feature in the pathophysiology of insulin resistance and type 2
      diabetes. We will review the range of human clinical, animal, and cell studies
      that address the impact of vitamin D in skeletal muscle, and discuss the
      controversial issues. This is a vibrant field of research and one that continues
      to extend the frontiers of knowledge of vitamin D's broad functional repertoire.

PMID- 23169677
TI  - Abnormal infant pulmonary function in young children with neuroendocrine cell
      hyperplasia of infancy.
AB  - RATIONALE: Lung function in children with neuroendocrine cell hyperplasia of
      infancy (NEHI) and correlations with future clinical outcomes are needed to guide
      clinical management. OBJECTIVE: To compare results of infant pulmonary function
      tests (IPFTs) in children with NEHI to disease control (DC) subjects and to
      correlate NEHI IPFTs with future outcomes. METHODS: We performed a retrospective,
      single center study of IPFT in subjects diagnosed by lung biopsy (NEHI) or
      clinically (NEHI syndrome) and in DC subjects evaluated for cancer or pre
      hematopoietic stem cell transplantation (HSCT). Raised volume rapid
      thoracoabdominal compression (RVRTC) and plethysmography were performed on all
      infants and evaluated for quality. Standard spirometry measures, room air oxygen
      saturations (RA O2 sat), and weight percentiles were collected during follow up.
      MEASUREMENTS AND MAIN RESULTS: Fifty-seven IPFTs were performed in 15 NEHI, 22
      NEHI syndrome, and 20 DC subjects. RVRTC and FRC measurements were obtained in
      85% or more of subjects in all groups. Significant airflow limitation (FEV0.5 P
      value <= 0.01) and air trapping (FRC P-value <= 0.01) were seen in NEHI and NEHI
      syndrome subjects compared to DCs. No significant correlations were found between
      IPFT, oxygen use, RA O2 sat, and weight at the time of the IPFTs. Initial FEV0.5
      and FRC z-scores correlated with RA O2 sat (r = 0.60 and -0.49) at short-term
      follow up (6-12 months). Most measurements of RVRTC correlated with FEV1 (n = 5)
      measured 4-5 years later (r > 0.50). CONCLUSIONS: IPFTs in NEHI subjects are
      feasible, demonstrate significant obstruction and air trapping, and correlate
      with future RA O2 sat and FEV1 . IPFTs may provide valuable clinical information
      when caring for NEHI patients. Pediatr Pulmonol. 2013; 48:1008-1015. (c) 2012
      Wiley Periodicals, Inc.

PMID- 23169678
TI  - Highly efficient p-type dye-sensitized solar cells based on tris(1,2
      diaminoethane)cobalt(II)/(III) electrolytes.
AB  - Co-produced: using [Co(en)(3)](2+/3+) based-electrolytes in p-type dye-sensitized
      solar cells (p-DSCs) gives record energy conversion efficiencies of 1.3 % and
      open-circuit voltages up to 709 mV under simulated sun light. The increase in
      photovoltage is due to the more negative redox potential of [Co(en)(3)](2+/3+)
      compared to established mediators.

PMID- 23169679
TI  - Pain-like behaviour and spinal changes in the monosodium iodoacetate model of
      osteoarthritis in C57Bl/6 mice.
AB  - BACKGROUND: Osteoarthritis (OA) is a highly prevalent, age-related pain condition
      that poses a significant clinical problem. Here, in the monosodium iodoacetate
      (MIA) model of OA, we have characterized pain behaviours and associated changes
      at the first pain synapse in the dorsal horn of the spinal cord. METHODS: Mice
      received intra-articular injections of 0.5, 0.75 and 1 mg MIA and mechanical paw
      withdrawal threshold was monitored for up to 4 weeks. An intrathecal injection of
      peptide antagonist calcitonin gene-related peptide (CGRP8-37 ) was given 3 weeks
      post MIA and paw withdrawal thresholds were measured after 1 and 3 h.
      Immunohistochemical analysis of the lumbar dorsal horn was carried out and
      activity-evoked CGRP release was measured from isolated lumbar dorsal horn slices
      - with dorsal roots attached. RESULTS: By 2 weeks after intra-articular MIA
      injection, mechanical hypersensitivity was established in the ipsilateral
      hindpaw. There was no evidence of sensory neuron damage in lumbar dorsal root
      ganglia 7 days after 1 mg MIA. However, both dorsal horn neuron activation and
      microglial response (Fos and Iba-1 immunostaining) but not reactive astrocytes
      (glial fibrillary acidic protein) were observed. Evoked CGRP release was greater
      from dorsal horn slices of MIA-treated mice compared with control. Furthermore,
      intrathecal administration of peptide antagonist CGRP8-37 acutely attenuated
      established MIA-induced mechanical hypersensitivity. CONCLUSIONS: Intra-articular
      MIA is associated with referred mechanical hypersensitivity and increased release
      of CGRP from primary afferent fibres in the dorsal horn where second-order neuron
      activation is associated with a microglial response. Antagonism of CGRP receptor
      activation provides a therapeutic avenue for the treatment of pain in OA.

PMID- 23169680
TI  - Impact of peptide micropatterning on endothelial cell actin remodeling for cell
      alignment under shear stress.
AB  - HSVEC behavior under physiological shear stress in vitro is investigated on PET
      surfaces micropatterned with both RGDS and WQPPRARI peptides. This technique
      allows (i) creating geometries on surface to guide cell orientation under shear
      stress and (ii) controlling surface chemical composition in order to modulate
      cell behavior. Under shear stress, endothelial cells adhere on patterned PET
      surfaces and present a more rapid orientation in flow direction in comparison to
      cells cultured on homogeneous surfaces. Micropatterned surfaces presenting a
      large surface area ratio of RGDS/WQPPRARI peptides induce fibrillar adhesion,
      while surfaces presenting an equal RGDS/WQPPRARI peptides surface area ratio
      preferentially induce focal adhesion.

PMID- 23169681
TI  - Editorial comment: Uni- or bilateral antegrade cerebral perfusion: that is the
      question!

PMID- 23169682
TI  - Duplication 12p and Pallister-Killian syndrome: a case report and review of the
      literature toward defining a Pallister-Killian syndrome minimal critical region.
AB  - Pallister-Killian syndrome (PKS) is a multisystem sporadic genetic condition
      characterized by facial anomalies, variable developmental delay and intellectual
      impairment, hypotonia, hearing loss, seizures, pigmentary skin differences,
      temporal alopecia, diaphragmatic hernia, congenital heart defects, and other
      systemic abnormalities. PKS is typically caused by the presence of a
      supernumerary isochromosome composed of the short arms of chromosome 12 resulting
      in tetrasomy 12p, which is often present in a tissue limited mosaic state. The
      PKS phenotype has also often been observed in individuals with complete or
      partial duplications of 12p (trisomy 12p rather than tetrasomy 12p) as the result
      of an interstitial duplication or unbalanced translocation. We have identified a
      proposita with PKS who has two small de novo interstitial duplications of 12p
      which, along with a review of previously reported cases, has allowed us to define
      a minimum critical region for PKS.

PMID- 23169683
TI  - Fraction of exhaled nitric oxide (FeNO ) norms in healthy North African children
      5-16 years old.
AB  - AIMS: (i) To identify factors that influence the FeNO values in healthy North
      African, Arab children aged 6-16 years; (ii) to test the applicability and
      reliability of the previously published FeNO norms; and (iii) if needed, to
      establish FeNO norms in this population, and to prospectively assess its
      reliability. POPULATION AND METHODS: This was a cross-sectional analytical study.
      A convenience sample of healthy Tunisian children, aged 6-16 years was recruited.
      First subjects have responded to two questionnaires, and then FeNO levels were
      measured by an online method with electrochemical analyzer (Medisoft, Sorinnes
      [Dinant], Belgium). Anthropometric and spirometric data were collected. Simple
      and a multiple linear regressions were determined. The 95% confidence interval
      (95% CI) and upper limit of normal (ULN) were defined. RESULTS: Two hundred
      eleven children (107 boys) were retained. Anthropometric data, gender,
      socioeconomic level, obesity or puberty status, and sports activity were not
      independent influencing variables. Total sample FeNO data appeared to be
      influenced only by maximum mid expiratory flow (l sec(-1) ; r(2)  = 0.0236, P =
      0.0516). For boys, only 1st second forced expiratory volume (l) explains a slight
      (r(2)  = 0.0451) but significant FeNO variability (P = 0.0281). For girls, FeNO
      was not significantly correlated with any children determined data. For North
      African/Arab children, FeNO values were significantly lower than in other
      populations and the available published FeNO norms did not reliably predict FeNO
      in our population. The mean +/- SD (95% CI ULN, minimum-maximum) of FeNO (ppb)
      for the total sample was 5.0 +/- 2.9 (5.4, 1.0-17.0). For North African, Arab
      children of any age, any FeNO value greater than 17.0 ppb may be considered
      abnormal. Finally, in an additional group of children prospectively assessed, we
      found no child with a FeNO higher than 17.0 ppb. CONCLUSION: Our FeNO norms
      enrich the global repository of FeNO norms the pediatrician can use to choose the
      most appropriate norms based on children's location or ethnicity.

PMID- 23169684
TI  - Simultaneous measurement of SUMOylation using SNAP/CLIP-tag-mediated translation
      at the single-molecule level.
AB  - Two opposing SUMO wrestlers: simultaneous measurement of multiple SUMOylations
      was achieved at the single-molecule level by integrating SNAP/CLIP-tag-mediated
      translation with single-molecule detection (SUMO=small ubiquitin-like modifier).
      This method gives exceptional sensitivity, and is capable of measuring the
      SUMOylation of different proteins under various physiological conditions.

PMID- 23169685
TI  - Longitudinal patterns of analgesic and central acting drug use and associated
      effectiveness in fibromyalgia.
AB  - BACKGROUND: We describe the changing pattern of analgesic and new central acting
      drug (NCAD) use (pregabalin, duloxetine, milnacipran) in fibromyalgia and measure
      NCAD effectiveness in clinical practice. METHODS: About 3123 US adult patients
      with fibromyalgia participated in an 11-year longitudinal study of fibromyalgia
      outcomes. We assessed severity-adjusted treatment prevalence and measured the
      effect of any use of NCAD on pain and fatigue, and functional status using the
      Health Assessment Questionnaire (HAQ) disability index. RESULTS: In 2010, 46.7%
      of patients used opioids, including 12.5% who used strong opioids. During the 11
      years, severity-adjusted strong opioid use increased from 6.3% to 11.7% and any
      opioid use from 40.0% to 46.6%. Nonsteroidal anti-inflammatory drug (NSAID) use
      decreased from 74% to 44%. Tricyclic use dropped in half, from 27% to 15%, while
      NCAD use increased from less than 10% to 39%. The estimated 25th and 50th
      percentiles for NCAD discontinuation time were 1 and 2.5 years. Overall pain,
      fatigue and HAQ scores were unchanged over the 11 years. For patients treated
      with NCAD, pain scores were reduced significantly by 0.17 (0.03, 0.30) units
      following the start of NCAD, an improvement of 2.8%. Some sensitivity analyses
      showed improvements of up to 4.3%. There was no significant improvement in
      fatigue or functional status. CONCLUSIONS: There is a changing pattern of drug
      treatment in fibromyalgia, consisting mostly of decreased NSAID and amitriptyline
      use and an increase in NCAD. Drug costs are substantially higher because of NCAD
      use, but we found no evidence of clinical benefit for NCAD compared with prior
      therapy.

PMID- 23169686
TI  - Glycogen as a biodegradable construction nanomaterial for in vivo use.
AB  - It is demonstrated that glycogen as a biodegradable and inexpensive material
      coming from renewable resources can be used as a carrier for the construction of
      in vivo imaging nanoagents. The model system considered is composed of glycogen
      modified with gadolinium and fluorescent labels. Systematic studies of properties
      of these nanocarriers by a variety of physical methods and results of in vivo
      tests of biodegradability are reported. This represents, to the authors' best
      knowledge, the first such use of glycogen.

PMID- 23169687
TI  - The layered structure of [Na(NH3)4][Indenide] containing a square-planar
      Na(NH3)4(+) cation.
AB  - It's hip to be a square! The ammines [Li(NH(3))(4)][Ind] and [Na(NH(3))(4)][Ind]
      both contain a cation coordinated by four ammonia molecules. Whereas the first
      shows the anticipated tetrahedral coordination, in the second the metal
      coordination is unexpectedly square-planar. The solvent-separated ion pair forms
      a rippled layer structure of alternating planar Na(NH(3))(4)(+) cations and
      indenyl carbanions that is attributed to NH(3) ???pi hydrogen bonds.

PMID- 23169688
TI  - Seizure characteristics in Pallister-Killian syndrome.
AB  - Pallister-Killian syndrome (PKS) is a congenital disorder attributed to
      supernumerary isochromosome 12p mosaicism. Craniofacial dysmorphism, learning
      impairment and seizures are considered cardinal features. However, little is
      known regarding the seizure and epilepsy patterns in PKS. To better define the
      prevalence and spectrum of seizures in PKS, we studied 51 patients (39 male, 12
      female; median age 4 years and 9 months; age range 7 months to 31 years) with
      confirmed 12p tetrasomy. Using a parent-based structured questionnaire, we
      collected data regarding seizure onset, frequency, timing, semiology, and
      medication therapy. Patients were recruited through our practice, at PKS Kids
      family events, and via the PKS Kids website. Epilepsy occurred in 27 (53%) with
      23 (85%) of those with seizures having seizure onset prior to 3.5 years of age.
      Mean age at seizure onset was 2 years and 4 months. The most common seizure types
      were myoclonic (15/27, 56%), generalized convulsions (13/27, 48%), and clustered
      tonic spasms (similar to infantile spasms; 8/27, 30%). Thirteen of 27 patients
      with seizures (48%) had more than one seizure type with 26 out of 27 (96%) ever
      having taken antiepileptic medications. Nineteen of 27 (70%) continued to have
      seizures and 17/27 (63%) remained on antiepileptic medication. The most commonly
      used medications were: levetiracetam (10/27, 37%), valproic acid (10/27, 37%),
      and topiramate (9/27, 33%) with levetiracetam felt to be "most helpful" by
      parents (6/27, 22%). Further exploration of seizure timing, in-depth analysis of
      EEG recordings, and collection of MRI data to rule out confounding factors is
      warranted.

PMID- 23169689
TI  - Discovery of Schaeffer's acid analogues as lead structures of mycobacterium
      tuberculosis type II dehydroquinase using a rational drug design approach.
AB  - Rational ligand design: Schaeffer's acid analogues were identified as novel
      inhibitors of M. tuberculosis type II dehydroquinase, a key enzyme of the
      shikimate pathway. Their likely binding mode was predicted using a combination of
      ensemble docking and flexible active site residues. Potentially, this scaffold
      could provide a good starting point for the design of antitubercular agents.

PMID- 23169690
TI  - A comparison of the effect of mindfulness and relaxation on responses to acute
      experimental pain.
AB  - BACKGROUND: This study aimed to investigate the efficacy of mindfulness training
      in comparison with relaxation training on pain, threshold and tolerance during
      the cold pressor task. METHODS: Undergraduate psychology students (n = 140) were
      randomly assigned to receive reassuring or threatening information about the cold
      pressor. Participants were then re-randomized to receive mindfulness or a control
      intervention: relaxation training. RESULTS: Analyses confirmed that the threat
      manipulation was effective in increasing worry, fear of harm and expectations of
      pain, and reducing coping efficacy. Interaction effects revealed that mindfulness
      was effective in increasing curiosity and reducing decentring under conditions of
      high threat but not low threat. Other interactions on cognitive variables
      (attentional bias to pain and self-focus) confirmed that mindfulness and
      relaxation appeared to exert influences under different conditions (i.e.
      mindfulness: high threat; and relaxation: low threat). Despite these cognitive
      effects being discerned under different conditions, there were no differences
      between mindfulness and relaxation on pain, tolerance or threshold in either
      threat group. CONCLUSIONS: These results show that a single, brief session of
      mindfulness based on body scanning is not sufficient to change the way in which
      individuals approach an experimental pain task in comparison with relaxation,
      which has previously been shown to be ineffective.

PMID- 23169691
TI  - Pallister-Killian syndrome: historical perspective and foreword.

PMID- 23169692
TI  - A study of cyanotetrazole oxides and derivatives thereof.
AB  - In this work we report on the syntheses of energetic salts of cyanotetrazolate-1-
      and -2-oxides; this offers a unique ability to compare the effects of tetrazole 1
      versus 2-oxidation. 5-Cyanotetrazolate-2-oxide can be synthesized by oxidation
      of the 5-cyanotetrazolate anion with Oxone, while the corresponding 1-oxide was
      synthesized by the rearrangement of azidoaminofurazan. Both chemical
      (multinuclear NMR, IR, and Raman spectroscopies, mass spectrometry, etc.) as well
      as explosive (impact, friction, and static sensitivities) properties are reported
      for these energetic salts. Calculated explosive performances using the EXPLO5
      computer code are also reported. We furthermore detail the chemistry of these two
      anions, and their ability to form tetrazole-carboxamides, dihydrotetrazines, and
      tetrazines. The ability to hydrolyze cyanotetrazole oxides to their amides was
      demonstrated by two copper complexes. Several crystal structures of these species
      are presented in addition to full chemical characterization. Finally, the unique
      1,4,-bis(2-N-oxidotetrazolate)-1,2,4,5-tetrazine anion was characterized as an
      energetic material as its ammonium salt.

PMID- 23169693
TI  - The relationship between acceptance, catastrophizing and illness representations
      in chronic pain.
AB  - BACKGROUND: Cognitive- and acceptance-based approaches are used to help people
      live with chronic pain. Little is known about how these constructs relate to each
      other. In this study, we examined how cognitive representations of chronic pain
      relate to interpersonal styles such as catastrophizing and the behavioural
      process of acceptance of chronic pain. This study further examined how these
      processes relate to emotional and physical functioning in chronic pain. METHODS:
      A cross-sectional design, employing validated questionnaires, was used to measure
      pain, emotional and physical dysfunction, illness representations,
      catastrophizing and acceptance in a heterogeneous sample of 150 chronic pain
      sufferers. RESULTS: The psychological variables significantly mediated the impact
      of pain severity on both emotional and physical dysfunction. In addition, a
      distinct pattern of mediation was observed. The relationship between pain and
      emotional dysfunction was mediated by representations of pain as a highly emotive
      experience and by catastrophizing; acceptance did not mediate this relationship.
      By contrast, the relationship between pain and physical dysfunction was mediated
      by acceptance and representations of high consequences of chronic pain, but not
      by catastrophizing. CONCLUSIONS: Pain severity itself is a relatively poor
      predictor of emotional and physical dysfunction in chronic pain states. These
      relationships are significantly mediated by psychological variables. Different
      approaches to chronic pain rehabilitation emphasize different targets (changing
      illness representations and reducing catastrophizing vs. acceptance and
      behavioural activation). This cross-sectional study suggests that these processes
      may differentially influence outcomes, but that they are complex and overlapping.
      Theoretical and clinical implications are discussed.

PMID- 23169694
TI  - Bilateral and unilateral adrenal incidentalomas: biochemical and clinical
      characteristics.
AB  - OBJECTIVE: The possible different prevalence of arterial hypertension (AH), type
      2 diabetes mellitus (T2DM), dyslipidaemia (DL) and vertebral fractures (FX)
      between patients with bilateral and unilateral adrenal incidentalomas (BAI and
      UAI, respectively) with and without subclinical hypercortisolism (SH) is unknown.
      In this study we compared the prevalence of AH, T2DM, DL and FX in BAI and UAI
      patients in relation to SH. DESIGN: Prospective study. METHODS: In 175 UAI and 38
      BAI patients, we evaluated BMI, spinal and femoral bone mineral density (LS and
      FN BMD, respectively) and the presence of AH, T2DM, DL and FX. SH was diagnosed
      in the presence of 2 of the following: urinary free cortisol levels >193 nmol/24
      h, serum cortisol levels after 1 mg dexamethasone suppression test >83 nmol/l or
      ACTH levels <2.2 pmol/l. RESULTS: Age, BMI and cortisol secretion were
      comparable, while FN BMD was lower in BAI than in UAI patients (-0.45+/-0.86 vs
      0.09+/-1.07, P=0.004). The prevalence of SH, AH, T2DM, and DL was comparable,
      while the prevalence of FX was higher in BAI than in UAI (52.6 vs 28%, P=0.007).
      The presence of FX was associated with BAI (odds ratio (OR) 2.6, 95% confidence
      interval (95% CI) 1.2-5.6, P=0.016), after adjusting for SH (OR 1.77, 95% CI 0.85
      3.7, P=0.12), BMI (OR 1.06, 95% CI 0.98-1.13, P=0.1), age (OR 1.07, 95% CI 1.04
      1.11, P=0.0001) and LS BMD (OR 1.31, 95% CI 1.03-1.67, P=0.03). CONCLUSION: BAI
      patients have an increased FX risk than UAI ones. Further studies should
      investigate the causes of bone involvement in BAI patients.

PMID- 23169695
TI  - Effect of short-term GH and testosterone administration on body composition and
      glucose homoeostasis in men receiving chronic glucocorticoid therapy.
AB  - OBJECTIVE: Long-term pharmacological glucocorticoid (GC) therapy leads to
      skeletal muscle atrophy and weakness. The objective of this study was to
      investigate whether short-term treatment with GH and testosterone (T) can
      increase lean mass without major impairment of glucose homoeostasis in patients
      on GC therapy. DESIGN, MATERIALS AND METHODS: This was a prospective, open-label,
      randomised, crossover study. Twelve men (age 74+/-6 years) on chronic GC
      treatment participated. The effects of 2 weeks' treatment with GH, testosterone
      and the combination of both on lean body mass (LBM), appendicular skeletal muscle
      mass (ASMM), extracellular water (ECW), body cell mass (BCM) and plasma glucose
      concentrations were investigated. RESULTS: LBM increased significantly after GH
      (Delta1.7+/-1.4 kg; P=0.007) and GH+testosterone (Delta2.4+/-1.1 kg; P=0.003),
      but not testosterone alone. ASMM increased after all three treatment periods; by
      1.0+/-0.8 kg after GH (P=0.005), 1.7+/-0.4 kg after GH+testosterone (P=0.002) and
      0.8+/-1.0 kg after testosterone (P=0.018). The increase in ASMM was larger with
      combined treatment than either GH or testosterone alone (P<0.05). ECW increased
      significantly after GH+testosterone by 1.5+/-2.6 l (P=0.038) but not after GH or
      testosterone alone. BCM increased slightly after single and combined treatments,
      but the changes were not significant. Fasting glucose increased significantly
      after GH (Delta0.4+/-0.4 mmol/l, P=0.006) while both fasting (Delta0.2+/-0.3
      mmol/l, P=0.045) and post glucose-load (Delta1.8+/-2.3 mmol/l, P=0.023) plasma
      glucose concentrations increased after GH+testosterone. CONCLUSIONS: GH and
      testosterone induce favourable and additive body compositional changes in men on
      chronic, low-dose GC treatment. In the doses used, combination therapy increases
      fasting and postprandial glucose concentration.

PMID- 23169696
TI  - Two novel mutations of the calcium-sensing receptor gene affecting the same amino
      acid position lead to opposite phenotypes and reveal the importance of p.N802 on
      receptor activity.
AB  - OBJECTIVE: Gain-of-function mutations of the calcium-sensing receptor (CASR) gene
      have been identified in patients with sporadic or familial autosomal dominant
      hypocalcemia (ADH). Inactivating mutations of the CASR gene cause familial
      hypocalciuric hypercalcemia (FHH). Here, we report two novel CASR mutations
      affecting the same amino acid (p.N802); one causes ADH and the other atypical
      FHH. PATIENTS AND METHODS: The first patient, an 11-year-old girl suffering from
      hypocalcemia, developed nephrocalcinosis when she was only 5 years old. The
      second patient is a 30-year-old woman who presented with mild hypercalcemia. PCR
      amplification of CASR coding exons and direct sequencing of PCR products were
      used to identify mutations. Site-directed mutagenesis was used to generate
      mutated CASR cDNAs in an expression plasmid. Using the MAPK assay system and
      transient transfection of Cos-7 cells with wild-type (WT) and mutated CASR, we
      studied the responses of these mutated receptors to extracellular Ca(2+) and to
      the negative allosteric CASR modulator, NPS2143. RESULTS: Two heterozygous
      missense mutations (p.N802I and p.N802S) affecting a residue in the sixth
      transmembrane domain of CASR were identified. In functional tests, the response
      of the p.N802S mutant to calcium was typical of an inactivating mutation.
      However, the p.N802I mutant had 70% of the maximally stimulated WT receptor
      activity even in the absence of extracellular calcium. This constitutive activity
      was only partially inhibited by the inhibitor, NPS2143. CONCLUSIONS: The
      asparagine at amino acid position 802 appears to be essential for the activity of
      the CASR protein and is implicated in the mechanism of CASR signaling.

PMID- 23169697
TI  - Immobilization of a molecular cobaloxime catalyst for hydrogen evolution on a
      mesoporous metal oxide electrode.

PMID- 23169698
TI  - Association of interactions among the IRF6 gene, the 8q24 region, and maternal
      folic acid intake with non-syndromic cleft lip/palate in Mexican Mestizos.

PMID- 23169699
TI  - Synergetic effects of in situ formed CaH2 and LiBH4 on hydrogen storage
      properties of the Li-Mg-N-H system.
AB  - Hydrogen storage properties and mechanisms of the Ca(BH(4))(2)-doped Mg(NH(2))(2)
      2LiH system are systematically investigated. It is found that a metathesis
      reaction between Ca(BH(4))(2) and LiH readily occurs to yield CaH(2) and LiBH(4)
      during ball milling. The Mg(NH(2))(2) -2LiH-0.1Ca(BH(4))(2) composite exhibits
      optimal hydrogen storage properties as it can reversibly store more than 4.5 wt%
      of H(2) with an onset temperature of about 90  degrees C for dehydrogenation and
      60  degrees C for rehydrogenation. Isothermal measurements show that
      approximately 4.0 wt% of H(2) is rapidly desorbed from the Mg(NH(2))(2) -2LiH
      0.1Ca(BH(4))(2) composite within 100 minutes at 140  degrees C, and
      rehydrogenation can be completed within 140 minutes at 105  degrees C and 100 bar
      H(2). In comparison with the pristine sample, the apparent activation energy and
      the reaction enthalpy change for dehydrogenation of the Mg(NH(2))(2)-2LiH
      0.1Ca(BH(4))(2) composite are decreased by about 16.5% and 28.1%, respectively,
      and thus are responsible for the lower operating temperature and the faster
      dehydrogenation/hydrogenation kinetics. The fact that the hydrogen storage
      performances of the Ca(BH(4))(2)-doped sample are superior to the individually
      CaH(2)- or LiBH(4)-doped samples suggests that the in situ formed CaH(2) and
      LiBH(4) provide a synergetic effect on improving the hydrogen storage properties
      of the Mg(NH(2))(2)-2LiH system.

PMID- 23169700
TI  - Biophysical study on the interaction of ceftriaxone sodium with bovine serum
      albumin using spectroscopic methods.
AB  - The interaction of ceftriaxone sodium (CS), a cephalosporin antibiotic, with the
      major transport protein, bovine serum albumin (BSA), was investigated using
      different spectroscopic techniques such as fluorescence, circular dichroism (CD),
      and UV-vis spectroscopy. Values of binding parameters for BSA-CS interaction in
      terms of binding constant and number of binding sides were found to be 9.00 *
      10(3), 3.24 * 10(3), and 2.30 * 10(3) M(-1) at 281, 301, and 321 K, respectively.
      Thermodynamic analysis of the binding data obtained at different temperatures
      showed that the binding process was spontaneous and was primarily mediated by van
      der Waals force or hydrogen bonding. CS binding to BSA caused secondary
      structural alterations in the protein as revealed by CD results. The distance
      between CS and Trp of BSA was determined as 3.23 nm according to the Forster
      resonance energy transfer theory.

PMID- 23169701
TI  - Vanadium distribution in four-component Mo-V-Te-Nb mixed-oxide catalysts from
      first principles: how to explore the numerous configurations?

PMID- 23169702
TI  - A 0.7 Mb de novo duplication at 7q21.3 including the genes DLX5 and DLX6 in a
      patient with split-hand/split-foot malformation.
AB  - Split-hand/split-foot malformation (SHFM1) has been reported to be caused by
      deletions, duplications or rearrangements involving the 7q21.3 region harboring
      DSS1, DLX5, and DLX6. We report on a female patient with unilateral syndactyly of
      the third and fourth fingers of the right hand and overgrowth and lateral
      deviation of the right great toe. There was a split foot malformation on the
      right, with absent fifth toe. The left hand was apparently normal and left foot
      was intact. The patient has no hearing loss. We performed conventional G-banding
      karyotype analysis, array comparative genomic hybridization (aCGH) and
      fluorescence in situ hybridization (FISH). G-banding karyotype result was normal
      46,XX. However, a duplication of 719 kb (96,303,736-97,022,335; NCBI
      build36/hg18, March 2006) was identified at the 7q21.3 region by aCGH. The array
      result was also confirmed by FISH analysis. The duplicated region harbors only
      DLX5 and DLX6, which are known for their role in SHFM1. Additionally, FISH
      analysis of parental samples showed de novo origin of this abnormality in the
      patient. This is the first report that highlights the duplication of 719 kb at
      7q21.3, harboring only DLX5 and DLX6 associated with the SHFM1 phenotype.

PMID- 23169703
TI  - Crop-derived polysaccharides as binders for high-capacity silicon/graphite-based
      electrodes in lithium-ion batteries.
AB  - Rice to power: Amylopectin is a major component of agricultural products such as
      corn, potato, and rice. Silicon-graphite electrodes are prepared by using
      slurries of these polysaccharides as binders. Compared to the conventionally used
      binder PVdF, they exhibit drastically improved electrode performance in Li cells.
      The improved performance is coupled to the degree of branching.

PMID- 23169705
TI  - 5(4H)-oxazolones as intermediates in the carbodiimide- and cyanamide-promoted
      peptide activations in aqueous solution.
AB  - The early days: although considered a species to be avoided in peptide chemistry,
      the intermediacy of 5(4H)-oxazolones is demonstrated to be essential for the
      formation of peptides through cyanamide and carbodiimide activation in aqueous
      solution.

PMID- 23169708
TI  - MRI for evaluation of myeloid sarcoma in adults: a single-institution 10-year
      experience.
AB  - OBJECTIVE: The purpose of this study was to evaluate the utilization and role of
      MRI in the management of myeloid sarcoma in adults. MATERIALS AND METHODS: A
      retrospective study of 69 patients with pathologically proven myeloid sarcoma
      included 25 patients (16 men, nine women; mean age, 55 years; range, 22-78 years)
      who underwent pretreatment MRI at our institution from January 2001 to October
      2011. A total of 71 MRI examinations were evaluated by two radiologists in
      consensus. RESULTS: A total of 41 sites of involvement of myeloid sarcoma were
      noted, most commonly bone (13/25, 52%), muscle (7/25, 28%), CNS (6/25, 24%), and
      head and neck (6/25, 24%). Nineteen sites were noted on MR images obtained for
      evaluation of a new sign or symptom, most commonly musculoskeletal (11 sites) and
      CNS (six sites). Fifteen sites were noted on MR images obtained for further
      evaluation of a previously detected abnormality, most commonly in the abdomen and
      pelvis (seven sites). Seven lesions were incidentally found on MR images obtained
      for other myeloid sarcoma-related indications, most commonly in the head and neck
      (three lesions) and musculoskeletal system (three lesions). The mean size of
      measurable lesions was 5.6 cm (range, 1-20 cm). Compared with muscle, the lesions
      were isointense (31/41, 75.6%) or hypointense (10/41, 24.4%) on T1-weighted
      images and mildly hyperintense (39/41, 95.1%) on T2-weighted images and had
      homogeneous enhancement (29/38, 76.3%). CONCLUSION: In our experience, MRI was
      most often used for evaluation of bone, muscle, the CNS, and the head and neck
      region. MRI is useful for evaluation of new musculoskeletal and CNS findings and
      for further evaluation of known abdominopelvic masses. Incidental findings are
      often musculoskeletal or in the soft tissues of the head and neck.

PMID- 23169707
TI  - Postmortem whole-body MRI in traumatic causes of death.
AB  - OBJECTIVE: The aim of this study was to determine the sensitivity and specificity
      of postmortem whole-body MRI for typical injuries resulting from traumatic causes
      of death. MATERIALS AND METHODS: Forty cases of accidental death were evaluated
      with postmortem whole-body MRI. Imaging was conducted according to a standard
      protocol, and each examination had an average duration of 90 minutes. The imaging
      findings were correlated with the autopsy findings, which served as the reference
      standard. RESULTS: MRI showed the main pathologic process leading to death in 39
      of the 40 cases. The sensitivity of postmortem MRI ranged from 100%
      (pneumothorax) to 40% (fractures of the upper extremities). In general, MRI had a
      high level of performance for depicting soft-tissue lesions, such as subcutaneous
      hematoma (e.g., galeal hematoma with a sensitivity 95%). The sensitivity of MRI
      was remarkably lower for lesions of the upper abdominal organs (liver, 80%;
      spleen, 50%; pancreas, 60%; kidneys, 66%). CONCLUSION: Postmortem whole-body MRI
      had overall good performance for depicting traumatic findings in corpses and
      therefore may serve an important role as an adjunct to classic autopsy for the
      forensic examination of cases of traumatic cause of death. However, the reduced
      sensitivity of postmortem MRI for lacerations of the upper abdominal organs and
      the observed superimposition of antemortem findings and postmortem findings
      (e.g., in the pulmonary tissue) in this retrospective study suggest that whole
      body postmortem MRI not be recommended as a replacement for classic autopsy.

PMID- 23169709
TI  - Imaging of trauma: Part 1, Pseudotrauma of the spine--osseous variants that may
      simulate injury.
AB  - OBJECTIVE: Anatomic variants and incomplete ossification and fusion of the
      developing spine may result in an erroneous diagnosis of injury or disease. This
      article reviews some of the more common imaging findings that may present as
      pseudotrauma. Normal development of the spine is reviewed, including
      synchondroses and ossification centers. Imaging of common variants is presented,
      with a focus on CT. CONCLUSION: Recognition of the normal developing spine and
      variants can prevent an incorrect diagnosis of injury and inappropriate
      treatment.

PMID- 23169704
TI  - Genes of innate immunity and the biological response to inhaled ozone.
AB  - Ambient ozone has a significant impact on human health. We have made considerable
      progress in understanding the fundamental mechanisms that regulate the biological
      response to ozone. It is increasingly clear that genes of innate immunity play a
      central role in both infectious and noninfectious lung disease. The biological
      response to ambient ozone provides a clinically relevant environmental exposure
      that allows us to better understand the role of innate immunity in noninfectious
      airways disease. In this brief review, we focus on (1) specific cell types in the
      lung modified by ozone, (2) ozone and oxidative stress, (3) the relationship
      between genes of innate immunity and ozone, (4) the role of extracellular matrix
      in reactive airways disease, and (5) the effect of ozone on the adaptive immune
      system. We summarize recent advances in understanding the mechanisms that ozone
      contributes to environmental airways disease.

PMID- 23169710
TI  - Imaging of trauma: Part 2, Abdominal trauma and pregnancy--a radiologist's guide
      to doing what is best for the mother and baby.
AB  - OBJECTIVE: The pregnant trauma patient requires imaging tests to diagnose
      maternal injuries and diagnostic tests to evaluate the viability of her
      pregnancy. This article will discuss abdominal trauma in pregnancy and the
      specific role of diagnostic imaging. Radiation concerns in pregnancy will be
      addressed. CONCLUSION: Trauma is the leading cause of nonobstetric maternal
      mortality and a significant cause of fetal loss. Both major and minor trauma
      result in an increased risk of fetal loss. In major trauma, when there is concern
      for maternal injury, CT is the mainstay of imaging. The risks of radiation to the
      pregnancy are small compared with the risk of missed or delayed diagnosis of
      trauma. In minor trauma, when there is no concern for maternal injury but there
      is concern about the pregnancy, ultrasound is performed but is insensitive in
      diagnosing placental abruption. External fetal monitoring is used to dictate
      patient care.

PMID- 23169711
TI  - 80-kV pulmonary CT angiography with 40 mL of iodinated contrast material in lean
      patients: comparison of vascular enhancement with iodixanol (320 mg I/mL)and
      iomeprol (400 mg I/mL).
AB  - OBJECTIVE: The purpose of this article is to compare the vascular enhancement
      obtained with a low-kilovoltage pulmonary CT angiography (CTA) protocol in lean
      patients, using 40 mL of a moderate-concentration isoosmolar (iodixanol, 320 mg
      I/mL) and a high-concentration low-osmolar (iomeprol, 400 mg I/mL) iodinated
      contrast medium injected at the same iodine delivery rate. SUBJECTS AND METHODS:
      Forty-two lean patients (31 men and 11 women; body mass index, <= 23 kg/m(2))
      with suspected pulmonary embolism and non-small cell lung carcinoma underwent
      pulmonary CTA with a 64-MDCT scanner using a tube voltage of 80 kV. Twenty-three
      patients (54.8%) received 40 mL of iodixanol (320 mg I/mL) injected at a rate of
      5 mL/s, and the remaining 19 patients (45.2%) were administered an equal volume
      of iomeprol (400 mg I/mL) at a flow rate of 4 mL/s. Intraarterial density was
      measured in the common pulmonary artery trunk, the main right and left pulmonary
      arteries, lobar arteries, and at the segmental level, for a total of 15 regions
      of interest per patient. Intravascular enhancement homogeneity from central to
      subsegmental level was also assessed visually using a semiquantitative score (1 =
      poor, 2 = good, and 3 = excellent). RESULTS: The overall vascular density of
      pulmonary arteries down to the segmental level was significantly higher with
      iodixanol (320 mg I/mL) than with iomeprol (400 mg I/mL) (p = 0.036). Enhancement
      homogeneity was good with both contrast agents, with no statistically significant
      difference between them (p = 0.8966). CONCLUSION: In 80-kV pulmonary CTA of lean
      patients, higher intravascular enhancement can be achieved with 40 mL of
      iodixanol (320 mg I/mL) than with the same volume of iomeprol (400 mg I/mL), with
      good vessel conspicuity down to the subsegmental level.

PMID- 23169712
TI  - CT attenuation of the bronchial wall in patients with asthma: comparison with
      geometric parameters and correlation with function and histologic
      characteristics.
AB  - OBJECTIVE: The purposes of this study were to compare airway wall attenuation in
      subjects with asthma and subjects without asthma; to correlate this value with
      pulmonary function test results, standard bronchial CT parameters, and
      immunohistologic data; and to identify CT parameters that influence obstructive
      indexes. SUBJECTS AND METHODS: Bronchial airway wall attenuation was averaged
      over four bronchi in 27 subjects with asthma and 15 control subjects without
      asthma. The following five standard bronchial parameters also were assessed:
      lumen area, wall area, wall thickness, wall-to-lumen area ratio, and wall-to
      total area ratio (wall area percentage). These parameters were compared between
      groups and correlated with functional data. Ability to predict patient group with
      these parameters was determined by comparison of receiver operating
      characteristic curves and areas under the curve. The influence of the parameters
      on obstructive indexes was assessed by multivariate analysis. Correlations
      between wall attenuation value and histologic data were studied in 11 patients
      with asthma. RESULTS: Wall attenuation value was greater in patients with asthma
      (-322 +/- 79 HU) than in control subjects (-463 +/- 69 HU). Correlation
      coefficients of wall attenuation value with functional obstructive parameters
      were significant and greater than those obtained for any other CT parameter. The
      area under the curve of wall attenuation value was greater than that of bronchial
      lumen area and bronchial wall area. In the model of multiple regression that
      included wall attenuation value and wall-to-total area ratio, wall attenuation
      value was the only measurement that significantly influenced obstructive indexes
      (R(2) = 0.39-0.43). Wall attenuation value correlated with mast cell
      infiltration. CONCLUSION: Compared with the usual bronchial CT parameters, airway
      wall attenuation better differentiates patients with asthma from control subjects
      and better correlates with obstruction.

PMID- 23169713
TI  - Tuberculous lymphadenitis of the thorax: comparisons of imaging findings between
      patients with and those without HIV infection.
AB  - OBJECTIVE: The purpose of this study was to discern differences in the clinical
      and radiologic presentations of intrathoracic tuberculous lymphadenitis in adult
      patients with and those without HIV infection. MATERIALS AND METHODS: Between
      2000 and 2010, 66 patients (28 men, 38 women; mean age, 45 +/- 13.9 years) were
      found to have intrathoracic tuberculous lymphadenitis. Of these patients, 17
      (26%) (15 men, two women; mean age, 47 +/- 9.9 years) were HIV-seropositive.
      Thoracic CT scans were evaluated for involved lymph node stations, long-axis
      diameter of involved lymph nodes, presence of central necrosis in enlarged nodes,
      and other associated findings. RESULTS: In HIV-positive patients, tuberculous
      lymphadenitis had more multifocal (mean number of involved nodal stations, 8.4
      versus 3.6; p < 0.001) nodal involvement, had smaller nodes (mean long-axis
      diameter, 17 mm versus 21 mm; p = 0.004), and was more frequently associated with
      lung parenchymal lesions and extrathoracic lymph node and organ involvement (p <
      0.05) than in HIV-negative patients. Tuberculous lymphadenitis was the sole
      manifestation of tuberculous infection in 22 of 49 (45%) HIV-negative patients
      and in 2 of 17 (12%) HIV-positive patients (p = 0.018). CONCLUSION: Tuberculous
      lymphadenitis in patients with HIV infection is characterized by multiple-station
      lymphadenitis with extensive lung parenchymal, extrathoracic lymph node, and
      extrathoracic organ involvement.

PMID- 23169714
TI  - Systematic error in lung nodule volumetry: effect of iterative reconstruction
      versus filtered back projection at different CT parameters.
AB  - OBJECTIVE: Iterative reconstruction potentially can reduce radiation dose
      compared with filtered back projection (FBP) for chest CT. This is especially
      important for repeated CT scanning, as is the case in patients with indeterminate
      lung nodules. It is currently unknown whether absolute nodule volumes measured
      with iterative reconstruction are comparable to those measured with FBP. We
      compared nodule volumes measured with iterative reconstruction and FBP at
      different CT parameters. MATERIALS AND METHODS: An anthropomorphic chest phantom
      was scanned using a 256-MDCT scanner at various tube voltages and tube current
      time products. Raw data were reconstructed using FBP or a commercially available
      iterative reconstruction algorithm. Five inserted nodules with 100 HU
      radiodensity and different sizes (3, 5, 8, 10, and 12 mm) were measured by two
      observers using semiautomatic software. Volumetric nodule measurements were
      performed using thin-slice reconstructions. RESULTS: For very small nodules
      (volume, 14.1 mm(3); diameter, 3 mm), FBP and iterative reconstruction
      measurements exhibited large errors and overestimated the nodule size by up to
      160%. For larger nodules (volume, >= 65.4 mm(3); diameter, >= 5 mm), CT
      underestimated the actual size, but errors were small (within 25%) and remained
      small when the tube voltage and tube current-time product were reduced, even
      without iterative reconstruction. CONCLUSION: In a phantom model, no clinically
      relevant differences beyond reported interscan variation levels between lung
      nodule volumes were measured in nodules 5 mm or larger at reduced tube voltage
      and tube current-time product, with radiation dose reductions up to 90.6% for
      both FBP and iterative reconstruction, suggesting that it is safe to convert FBP
      protocols to iterative reconstruction and reduce tube voltage and tube current
      time product for lung nodule follow-up. CT appears to slightly underestimate
      actual nodule volume.

PMID- 23169715
TI  - Pulmonary 64-MDCT angiography with 30 mL of IV contrast material: vascular
      enhancement and image quality.
AB  - OBJECTIVE: The objective of our study was to determine whether vascular
      enhancement and image quality can be preserved in pulmonary CT angiography (CTA)
      performed on a 64-MDCT scanner with 30 mL of IV contrast material. MATERIALS AND
      METHODS: This retrospective matched-cohort study compared image quality of
      pulmonary CTA performed using 30 mL of IV contrast material versus 100 mL of IV
      contrast material. CT images of 50 patients (46 men, four women; mean age, 66
      years) who underwent pulmonary CTA on a 64-MDCT scanner using a low dose (30 mL)
      of iodixanol 320 and another 50 patients (49 men, one woman; mean age, 65 years)
      who underwent pulmonary CTA using a regular dose (100 mL) of contrast material
      during the same time period were selected for review. The 30- and 100-mL
      pulmonary CTA studies were retrospectively evaluated by two thoracic radiologists
      in random order. Attenuation values were recorded over the main, right main,
      selected lobar, segmental, and subsegmental pulmonary arteries. Image quality was
      also subjectively assessed using visual scores on a scale from 1 (nondiagnostic)
      to 5 (excellent). RESULTS: The average attenuation measurements of the main,
      right main, selected lobar, segmental, and subsegmental pulmonary arteries were
      260, 262, 280, 316, and 338 HU, respectively, on the 30-mL studies and 313, 301,
      316, 344, and 349 HU, respectively, on the 100-mL studies. The average visual
      score was 4.0 for both the 30- and 100-mL groups. A visual score of 4 or 5 was
      given to 82% of studies in the 30-mL group and 78% of studies in the 100-mL
      group. CONCLUSION: Contrast agent dose for pulmonary CTA using a 64-MDCT scanner
      can be significantly reduced without compromising diagnostic image quality.

PMID- 23169716
TI  - Radiography of pacemakers and implantable cardioverter defibrillators.
AB  - OBJECTIVE: The purpose of this article is to review the normal and abnormal
      radiographic appearances of cardiac pacemaker and implantable cardioverter
      defibrillator systems. CONCLUSION: Chest radiographs showing pacemakers and
      implantable cardioverter defibrillators contain identifying and clinically
      relevant information, such as MRI compatibility and possible malfunction.
      Accurate and timely reporting of these features provides important information
      that can improve patient care.

PMID- 23169717
TI  - Pneumatosis intestinalis and bowel perforation associated with molecular targeted
      therapy: an emerging problem and the role of radiologists in its management.
AB  - OBJECTIVE: The purpose of this article is to study the imaging features,
      management, and outcome of pneumatosis intestinalis and bowel perforation
      associated with molecular targeted therapy. MATERIALS AND METHODS: In this
      retrospective study, 48 patients with cancer who developed pneumatosis or
      intestinal perforation were found by searching a radiology database. Of these
      patients, 24 patients (13 women and 11 men; mean age, 61 years; range, 39-83
      years) receiving molecular targeted therapy without any confounding factors for
      pneumatosis or perforation were selected. Initial and follow-up CT scans were
      evaluated by two radiologists; medical records were reviewed to note clinical
      features, management, and outcome. RESULTS: Seventeen (70.8%) patients were
      asymptomatic. Colorectal cancer (n = 10) and renal cell carcinoma (n = 5) were
      the most common malignancies; bevacizumab (n = 14) and sunitinib (n = 6) were the
      most common associated drugs. Imaging findings included intestinal perforation
      (20 sites in 18 patients), pneumatosis (n = 10), ascites (n = 8),
      pneumoperitoneum (n = 7), fistula formation (n = 7), and fluid collections (six
      collections in five patients). Fifteen (62.5%) patients were treated
      conservatively, seven (29.2%) underwent surgery, and two (8.3%) underwent
      percutaneous drainage. Molecular targeted therapy was discontinued in 22 of 24
      patients; findings resolved in 19 patients, remained stable in one, and worsened
      in one. One patient died after surgery. In both instances where the drug was
      continued, the abnormality worsened. Findings recurred in three of four patients
      in whom the drug was restarted after initial resolution. CONCLUSION: Radiologists
      should be aware of intestinal complications associated with molecular targeted
      therapy, including pneumatosis, bowel perforation, and fistula formation. Most
      patients can be treated conservatively after discontinuation of molecular
      targeted therapy. Continuing or restarting molecular targeted therapy can cause
      worsening or recurrent pneumatosis or perforation.

PMID- 23169719
TI  - Portal vein embolization: cross-sectional imaging of normal features and
      complications.
AB  - OBJECTIVE: The purpose of this article is to describe the role of cross-sectional
      imaging before portal vein embolization, the normal imaging findings after the
      procedure, and the imaging findings of postprocedural complications. CONCLUSION:
      With the increasing emphasis on aggressive resection of hepatic malignancies,
      portal vein embolization has evolved into a leading technique. Radiologists need
      to be familiar with the normal imaging findings after this procedure and with the
      imaging findings of postprocedural complications.

PMID- 23169718
TI  - Abdominal CT with model-based iterative reconstruction (MBIR): initial results of
      a prospective trial comparing ultralow-dose with standard-dose imaging.
AB  - OBJECTIVE: The purpose of this study was to report preliminary results of an
      ongoing prospective trial of ultralow-dose abdominal MDCT. SUBJECTS AND METHODS:
      Imaging with standard-dose contrast-enhanced (n = 21) and unenhanced (n = 24)
      clinical abdominal MDCT protocols was immediately followed by ultralow-dose
      imaging of a matched series of 45 consecutively registered adults (mean age, 57.9
      years; mean body mass index, 28.5). The ultralow-dose images were reconstructed
      with filtered back projection (FBP), adaptive statistical iterative
      reconstruction (ASIR), and model-based iterative reconstruction (MBIR). Standard
      dose series were reconstructed with FBP (reference standard). Image noise was
      measured at multiple predefined sites. Two blinded abdominal radiologists
      interpreted randomly presented ultralow-dose images for multilevel subjective
      image quality (5-point scale) and depiction of organ-based focal lesions.
      RESULTS: Mean dose reduction relative to the standard series was 74% (median,
      78%; range, 57-88%; mean effective dose, 1.90 mSv). Mean multiorgan image noise
      for low-dose MBIR was 14.7 +/- 2.6 HU, significantly lower than standard-dose FBP
      (28.9 +/- 9.9 HU), low-dose FBP (59.2 +/- 23.3 HU), and ASIR (45.6 +/- 14.1 HU)
      (p < 0.001). The mean subjective image quality score for low-dose MBIR (3.0 +/-
      0.5) was significantly higher than for low-dose FBP (1.6 +/- 0.7) and ASIR (1.8
      +/- 0.7) (p < 0.001). Readers identified 213 focal noncalcific lesions with
      standard-dose FBP. Pooled lesion detection was higher for low-dose MBIR (79.3%
      [169/213]) compared with low-dose FBP (66.2% [141/213]) and ASIR (62.0%
      [132/213]) (p < 0.05). CONCLUSION: MBIR shows great potential for substantially
      reducing radiation doses at routine abdominal CT. Both FBP and ASIR are limited
      in this regard owing to reduced image quality and diagnostic capability. Further
      investigation is needed to determine the optimal dose level for MBIR that
      maintains adequate diagnostic performance. In general, objective and subjective
      image quality measurements do not necessarily correlate with diagnostic
      performance at ultralow-dose CT.

PMID- 23169720
TI  - Current update on cytogenetics, taxonomy, diagnosis, and management of
      adrenocortical carcinoma: what radiologists should know.
AB  - OBJECTIVE: A multimodality imaging spectrum of adrenocortical carcinoma, with an
      emphasis on both anatomic and functional imaging, will be reviewed. Recent
      advances in the molecular cytogenetics of this tumor and its impact on diagnosis,
      prognosis, and development of newer targeted therapy will be discussed in this
      article. CONCLUSION: Adrenocortical carcinomas are rare aggressive tumors
      associated with a poor prognosis. Awareness of the molecular behavior and
      spectrum of imaging features of this tumor can help in appropriate patient
      treatment.

PMID- 23169721
TI  - Hereditary renal tumor syndromes: imaging findings and management strategies.
AB  - OBJECTIVE: It is not rare for the radiologist to identify multiple renal masses
      and be the first to raise the possibility of a hereditary renal tumor syndrome.
      Characteristic renal and extrarenal imaging findings aid in making the correct
      diagnosis. The imaging findings, screening guidelines, and management techniques
      for the most common hereditary renal tumor syndromes are reviewed. CONCLUSION:
      Hereditary renal tumor syndromes have specific screening guidelines and unique
      management techniques in which imaging plays a central role.

PMID- 23169722
TI  - Incidental findings at initial imaging workup of patients with prostate cancer:
      clinical significance and outcomes.
AB  - OBJECTIVE: The purpose of this article is to evaluate the frequency and clinical
      relevance of incidental findings in patients with prostate cancer who underwent
      abdominopelvic contrast-enhanced CT examination for initial staging workup.
      MATERIALS AND METHODS: We retrospectively reviewed 355 initial staging
      abdominopelvic contrast-enhanced CT examinations conducted from January 2000 to
      December 2010 in patients with prostate cancer for incidental findings that were
      not related to prostate cancer. A finding was judged to be potentially
      significant if therapeutic intervention, additional imaging, or tissue sampling
      was deemed advisable. The rate of incidental findings was correlated to patients'
      age and stratified prostate cancer risk groups. RESULTS: We found 779 incidental
      finding in 292 patients (82.3%), of which 75 findings in 73 patients (20.6%) were
      potentially significant. Indeterminate masses were the most prevalent significant
      finding (n = 62). Synchronous malignancy was detected in 21 patients (5.9%).
      Kidney cancer (n = 7 [1.97%]) was the most common malignancy, followed by
      lymphoma (n = 4 [1.13%]). Staging of the cancers revealed that 15 patients,
      including all of those with renal cancer, had N0M0 disease. Significant vascular
      abnormalities were reported in six cases. Additionally, significant findings,
      synchronous malignancies in particular, were identified at a higher rate in
      patients older than 65 years. However, no significant differences were noticed
      between the different prostate cancer risk groups. CONCLUSION: Abdominal contrast
      enhanced CT for initial staging of prostate cancer shows a considerable
      prevalence of incidental vascular events and synchronous cancers, with kidney
      cancers being the most common. Notably, 71.5% of these malignancies were at early
      stage. Our results show an incremental value of CT in prostate cancer staging,
      with an emphasis on focused evaluation of the kidneys.

PMID- 23169723
TI  - Small renal oncocytomas: is segmental enhancement inversion a characteristic
      finding at biphasic MDCT?
AB  - OBJECTIVE: The purpose of this study was to retrospectively determine whether
      segmental enhancement inversion was a common and characteristic finding in small
      (<= 4 cm) renal oncocytomas on biphasic contrast-enhanced CT. MATERIALS AND
      METHODS: This retrospective case-control study included 16 patients with 16 renal
      oncocytomas and 15 control patients with 15 renal cell carcinomas (RCCs), matched
      for age and sex, who underwent biphasic contrast-enhanced MDCT at our
      institution. Three reviewers independently analyzed each tumor for enhancement
      patterns on MDCT, including the presence or absence of segmental enhancement
      inversion, homogeneity, and phase of peak enhancement. RESULTS: The mean and
      median sizes of the oncocytomas were 2.5 and 2.4 cm, respectively (range, 1.1-3.9
      cm), and the mean and median sizes of the RCCs were both 2.6 cm (range, 1.4-3.9
      cm). There was no significant difference in the size of the renal masses between
      the two groups (p = 0.50). For two reviewers, segmental enhancement inversion was
      not present in any of the renal masses; for one reviewer, segmental enhancement
      inversion was present in one oncocytoma (6%) and one RCC (7%). For all reviewers,
      there was no feature or enhancement pattern that was statistically significantly
      associated with renal oncocytoma or RCC (p < 0.05). CONCLUSION: Segmental
      enhancement inversion was not a common or characteristic CT finding for renal
      oncocytoma and was not helpful in differentiating small renal oncocytomas from
      RCC.

PMID- 23169724
TI  - Usefulness of the virtual monochromatic image in dual-energy spectral CT for
      decreasing renal cyst pseudoenhancement: a phantom study.
AB  - OBJECTIVE: The purpose of this study was to determine the effect that dual-energy
      spectral CT has on renal cyst pseudoenhancement with a renal cyst phantom.
      MATERIALS AND METHODS: Two renal compartments within a CT phantom were filled
      with 40- and 240-HU solutions of diluted contrast material, mimicking the
      nonenhanced phase and nephrographic phase of MDCT, respectively. A saline-filled
      tapering cylindric cyst model was used, simulating cysts of varying diameters
      (range, 0.7-3.0 cm) suspended in the renal compartments. The phantom was scanned
      using dual-energy CT (DECT) (80 and 140 kVp) and conventional, single-energy CT
      (120 kVp) with the same 64-MDCT scanner. Attenuation increase was measured for a
      cyst model within 40- and 240-HU dilutions. We compared the attenuation increase
      obtained on virtual monochromatic images from DECT with conventional, single
      energy MDCT images using a paired Student t test. RESULTS: Pseudoenhancement
      occurred in the conventional single-energy CT acquisitions, with water
      attenuation increase of 42.44 +/- 4.03 HU measured at 120 kVp. In virtual
      monochromatic images of DECT, we observed less pseudoenhancement with water
      attenuation increase of 21.51 +/- 6.18 HU at 70 keV. Both acquisitions yielded a
      p value less than 0.0001. CONCLUSION: We achieved less pseudoenhancement of renal
      cysts with virtual monochromatic images of DECT compared with conventional single
      energy CT. This method may be useful when an accurate differentiation between
      small renal cysts and solid masses is critical.

PMID- 23169725
TI  - Interrater agreement in the evaluation of discrepant imaging findings with the
      Radpeer system.
AB  - OBJECTIVE: The Radpeer system is central to the quality assurance process in many
      radiology practices. Previous studies have shown poor agreement between
      physicians in the evaluation of their peers. The purpose of this study was to
      assess the reliability of the Radpeer scoring system. MATERIALS AND METHODS: A
      sample of 25 discrepant cases was extracted from our quality assurance database.
      Images were made anonymous; associated reports and identities of interpreting
      radiologists were removed. Indications for the studies and descriptions of the
      discrepancies were provided. Twenty-one subspecialist attending radiologists
      rated the cases using the Radpeer scoring system. Multirater kappa statistics
      were used to assess interrater agreement, both with the standard scoring system
      and with dichotomized scores to reflect the practice of further review for cases
      rated 3 and 4. Subgroup analyses were conducted to assess subspecialist
      evaluation of cases. RESULTS: Interrater agreement was slight to fair compared
      with that expected by chance. For the group of 21 raters, the kappa values were
      0.11 (95% CI, 0.06-0.16) with the standard scoring system and 0.20 (95% CI, 0.13
      0.27) with dichotomized scores. There was disagreement about whether a
      discrepancy had occurred in 20 cases. Subgroup analyses did not reveal
      significant differences in the degree of interrater agreement. CONCLUSION: The
      identification of discrepant interpretations is valuable for the education of
      individual radiologists and for larger-scale quality assurance and quality
      improvement efforts. Our results show that a ratings-based peer review system is
      unreliable and subjective for the evaluation of discrepant interpretations.
      Resources should be devoted to developing more robust and objective assessment
      procedures, particularly those with clear quality improvement goals.

PMID- 23169727
TI  - New exposure indicators for digital radiography simplified for radiologists and
      technologists.
AB  - OBJECTIVE: The purpose of this article is to educate radiologists and
      technologists about the clinically relevant portion of the new digital
      radiography standards. CONCLUSION: Both the International Electrotechnical
      Commission (IEC standard 62494-1) and the American Association of Physicists in
      Medicine (AAPM Task Group 116) have developed similar standards for monitoring
      exposure in digital radiography to eliminate proprietary and confusing
      terminology. Radiologists and technologists will need to learn three new terms-
      exposure index, target exposure index, and deviation index--to understand the new
      standards.

PMID- 23169728
TI  - Embedding 3D radiology models in portable document format.
AB  - OBJECTIVE: The purpose of this article is to discuss how to convert cross
      sectional images into a 3D model and embed them in a Portable Document Format
      (PDF) file. Four programs are used: OsiriX, MeshLab, Microsoft PowerPoint, and
      Adobe Acrobat. Step-by-step instructions are provided. CONCLUSION: Embedding 3D
      radiology models into PDF files is a powerful tool that may be used for clinical,
      educational, and research purposes.

PMID- 23169726
TI  - Physicians' and midlevel providers' awareness of lifetime radiation-attributable
      cancer risk associated with commonly performed CT studies: relationship to
      practice behavior.
AB  - OBJECTIVE: The purpose of this study is to investigate emergency department (ED)
      providers' knowledge of the lifetime cancer risk attributable to radiation from
      commonly performed CT scans and its association with the ordering providers' risk
      benefit analysis before ordering the examination. This study further explores
      factors that may influence a provider's selection of a particular diagnostic
      imaging study in an ED setting. MATERIALS AND METHODS: Sixty-seven ED providers
      at the University of Rochester Medical Center completed a multiple-choice
      questionnaire. The questions were derived to assess an individual provider's
      awareness of lifetime cancer risk attributable to radiation from a diagnostic CT
      scan of the abdomen or pelvis and the provider's behavior toward risk-benefit
      analysis before ordering the examination. The association between the questions
      and years since completion of clinical training was determined using the Spearman
      correlation test. Univariate logistic regression analysis was used for the same
      questions to predict the knowledge of lifetime cancer risk attributable to
      radiation. RESULTS: Fewer than 30% of ED providers possessed accurate knowledge
      of lifetime cancer risk attributable to radiation (p = 0.025). Providers with
      greater clinical experience, although lacking in the knowledge of lifetime cancer
      risk attributable to radiation, were more likely to consider patients' radiation
      dose history and to conduct a risk-benefit analysis and were less likely to order
      a CT scan unnecessarily. Clinical experience was negatively correlated with
      perceived unnecessary use of CT scans (p = 0.01). CONCLUSION: A large proportion
      of ED providers are unaware of the lifetime risk of carcinogenesis associated
      with commonly performed CT scans. Clinical experience, not knowledge of lifetime
      cancer risk attributable to radiation, is significantly associated with
      beneficial behavior toward the use of CT.

PMID- 23169729
TI  - Soft-tissue lesions: when can we exclude sarcoma?
AB  - OBJECTIVE: A wide spectrum of space-occupying soft-tissue lesions may be
      discovered on MRI studies, either as incidental findings or as palpable or
      symptomatic masses. Characterization of a lesion as benign or indeterminate is
      the most important step toward optimal treatment and avoidance of unnecessary
      biopsy or surgical intervention. CONCLUSION: The systemic MRI interpretation
      approach presented in this article enables the identification of cases in which
      sarcoma can be excluded.

PMID- 23169730
TI  - Vertebroplasty and kyphoplasty in the United States: provider distribution and
      guidance method, 2001-2010.
AB  - OBJECTIVE: The purpose of this study was to determine the utilization by
      specialty and guidance method for vertebral augmentation (including
      vertebroplasty and kyphoplasty) in the United States from 2001 to 2010. MATERIALS
      AND METHODS: Using the 2001 through 2010 United States part B Medicare claims
      database, we studied the CPT-4 (Current Procedural Terminology, 4th ed.) codes
      used for thoracic (22520) and lumbar (22521) vertebroplasty, thoracic (22523) and
      lumbar (22524) kyphoplasty, and the method of radiologic guidance (76012 for
      fluoroscopy and 76013 for CT). For each of these codes, volume and physician
      specialty were tabulated. RESULTS: Radiologists performed 73% of Medicare
      reimbursed vertebroplasty procedures in the United States in 2001-2010 and 30% of
      kyphoplasty procedures from 2006 to 2010. The majority were performed by
      nonradiologists, most notably orthopedic surgeons, who accounted for 40%.
      Although there was a decrease in utilization of vertebroplasty and kyphoplasty
      from 2009 to 2010, the number of vertebroplasties increased by 72.9% from 2001 to
      2010, and the number of kyphoplasties increased by 12.0% from 2006 to 2010.
      Fluoroscopy is nearly universal as a guidance method for both vertebroplasty and
      kyphoplasty. CONCLUSION: This study shows that despite controversy regarding the
      long-term efficacy of vertebral augmentation, including vertebroplasty and
      kyphoplasty, utilization has risen since these procedures have been instituted
      and fluoroscopy is nearly universal as a guidance method. For vertebroplasty, the
      decrease in utilization from 2007 to 2009 may be explained in part by a
      combination of the initiation of kyphoplasty codes in 2006 and the August 2009
      Kallmes et al. and Buchbinder et al. publications. Decreased utilization of both
      vertebroplasty and kyphoplasty from 2009 to 2010 may also be partly due to these
      publications.

PMID- 23169731
TI  - Quality outcomes of reinterpretation of brain CT studies by subspecialty experts
      in stroke imaging.
AB  - OBJECTIVE: The purposes of this study were to determine the clinical importance
      and relative value of reinterpretation of brain CT studies by subspecialty
      experts by assessing the accuracy of interpretation by general radiologists at
      primary stroke centers and to assess interpretive quality outcomes as a function
      of change in the treatment of patients with stroke diagnoses or acute
      presentations of suspected stroke. MATERIALS AND METHODS: Computerized medical
      records for the years 2009-2010 at four major community hospitals were queried
      for primary interpretation of brain CT studies of stroke patients with an acute
      presentation of either stroke or suspected stroke as diagnosed by board-certified
      general radiologists (nonneuroradiologists). A central database was queried that
      allowed one to query by clinical history or symptoms. Secondary interpretation of
      images of the identified patient sample was then performed by three experienced
      neuroradiologists. Each case was initially interpreted as an emergency or urgent
      study by a general radiologist. The reinterpretations performed by a
      neuroradiologist were scored as concordant or discordant. The discordant studies
      were categorized as a major discordance if there was a change in clinical
      management or as a minor discordance if there was no effect on or change in
      clinical management. The assessment was limited to brain CT studies without
      contrast administration. CT angiography and perfusion CT studies were not
      included in the analysis. Patients with hemorrhagic stroke, brain tumors,
      abscesses, and AIDS or HIV infection were excluded to limit the assessment to
      ischemic nonhemorrhagic disease. RESULTS: Of the 560 studies reviewed, 14 studies
      (2.5%) were identified as discordant. Of those discordant studies, four (0.7% of
      the original 560) were categorized as major discrepancies necessitating a change
      in clinical management. Ten (1.78%) were categorized as minor discrepancies, for
      which there was no change in management. There were no permanent adverse outcomes
      with respect to morbidity and mortality as a result of a discrepant
      interpretation, as determined by chart review or communication with the attending
      or referring physician by the secondary reader. CONCLUSION: Most of the
      interpreted head CT cases read by board-certified general radiologists for
      patients presenting with stroke or stroke symptoms did not result in discordant
      interpretations as verified by subspecialty experts. Discordant interpretations
      did not result in changes in clinical management in most cases. Double reading of
      head CT scans for these patients by subspecialty experts appears to be an
      inefficient method of substantially improving imaging health quality outcomes in
      stroke.

PMID- 23169732
TI  - CT perfusion imaging pitfall related to fetal posterior cerebral artery.
AB  - OBJECTIVE: The purpose of this article is to discuss how a unilateral fetal
      posterior cerebral artery (PCA) causes perfusion map asymmetry due to
      anteroposterior bolus arrival discrepancy. We performed region of interest
      analysis of asymmetric perfusion maps before and after delay correction was
      performed. CONCLUSION: Perfusion asymmetry becomes unapparent using a delay
      correction algorithm, indicating bolus arrival delay on the side opposite the
      fetal PCA. Delay correction algorithms can eliminate deconvolution errors related
      to bolus arrival delay.

PMID- 23169733
TI  - Role of 18F-FDG PET/CT in the diagnosis of clinically suspected Marjolin ulcer.
AB  - OBJECTIVE: The purpose of our study is to retrospectively determine the
      diagnostic role of (18)F-FDG PET/CT at the primary lesion site in burned patients
      with chronic nonhealing ulcers who are suspected of having Marjolin ulcers.
      MATERIALS AND METHODS: Thirty-three burn scar contractures with nonhealing
      chronic ulcer in 28 patients were included in this study. The lesions were sorted
      into two groups: 22 squamous cell carcinomas and one basal cell carcinoma were
      assigned to group 1 (Marjolin ulcer), and 10 lesions of chronic ulcer with
      inflammation and fibrosis were assigned to group 2. The maximum standardized
      uptake value (SUV(max)) and the lesion thickness and size for the two groups were
      evaluated. To determine the utility of PET/CT in the evaluation of invasion
      depth, we compared the imaging findings of PET/CT with surgical or pathologic
      results and the findings of additional imaging modalities, such as CT or MRI.
      RESULTS: The SUV(max) and the lesion thickness for group 1 were significantly
      higher than those for group 2 (p < 0.01 and p = 0.03, respectively). The
      sensitivity, specificity, and area under the receiver operating characteristic
      curve were 82.6%, 90%, and 0.900, respectively, for SUV(max) and 65.2%, 80%, and
      0.741, respectively, for lesion thickness. PET/CT was helpful and showed quite
      good correlation with surgical or pathologic results in determining invasion
      depth. CONCLUSION: PET/CT is useful in differentiating Marjolin ulcer from benign
      inflammatory conditions of chronic nonhealing ulcer in burn scars. It is also
      useful in the evaluation of the depth of invasion in Marjolin ulcer cases.

PMID- 23169734
TI  - Polytetrafluoroethylene-covered retrievable expandable nitinol stents for
      malignant esophageal obstructions: factors influencing the outcome of 270
      patients.
AB  - OBJECTIVE: The purpose of this study was to evaluate the clinical effectiveness
      of polytetrafluoroethylene (PTFE)-covered retrievable expandable nitinol stents
      in patients with malignant esophageal strictures and to identify prognostic
      factors associated with clinical outcomes. MATERIALS AND METHODS: From 2001 to
      2010, 320 PTFE-covered stents were placed in 270 patients. Technical and clinical
      success, complications, survival, and stent patency were measures of clinical
      effectiveness. The relationships among complications and age, sex, stricture
      location, stricture length, chemotherapy alone, chemoradiotherapy, and malignancy
      source were examined. Independent prognostic factors of overall survival and
      stent patency were identified. RESULTS: Stent placement and removal were
      technically successful and tolerated without procedural complications, and 98% of
      patients achieved clinical success. The complication rate was 30%. Two removed
      stents exhibited covering membrane separation. Chemotherapy was associated with
      increased stent migration (p = 0.002). Stricture location and chemoradiotherapy
      were associated with esophagorespiratory fistula development (p = 0.033 and p <
      0.001, respectively). Median and mean survival periods were 114 days (95% CI, 102
      126 days) and 166 days (138-193 days). Chemotherapy and chemoradiotherapy were
      independent prognostic factors for survival (p = 0.050 and p = 0.032,
      respectively). The median and mean stent patency periods were 60 days (41-79
      days) and 90 days (71-108 days). Chemoradiotherapy was the only independent
      prognostic factor for stent patency (p = 0.012). CONCLUSION: The PTFE-covered
      stents were clinically effective. Membrane degradation was not evident, although
      0.7% of the patients experienced covering membrane separation. Chemotherapy was
      associated with increased migration and prolonged survival. Chemoradiotherapy was
      associated with increased esophagorespiratory fistula formation and decreased
      stent patency.

PMID- 23169735
TI  - Fotemustine chemoembolization of hepatic metastases from uveal melanoma: a
      retrospective single-center analysis.
AB  - OBJECTIVE: The purpose of the current study was to retrospectively evaluate
      response and survival in patients with hepatic metastasis from uveal melanoma
      treated by palliative transarterial chemoembolization (TACE) with fotemustine.
      MATERIALS AND METHODS: During the study period, 21 patients with hepatic
      metastases from uveal melanoma were treated by TACE. A series of TACE
      interventions (mean number per patient, 3.29 interventions; range, 1-6
      interventions) was performed on each patient with an emulsion of fotemustine
      dissolved in 10 mL of saline mixed with 10 mL of an oily contrast agent. Tumor
      response based on the Response Evaluation Criteria in Solid Tumors was evaluated
      using contrast-enhanced CT scans obtained 6-10 weeks after embolization. RESULTS:
      CT showed partial regression after TACE in three patients (14%). Six patients
      (29%) presented with stable disease but no significant change in tumor size after
      TACE, and 12 patients (57%) presented with progressive disease after TACE
      treatment. The overall response rate was 43%. The mean survival after diagnosis
      of hepatic metastasis was 28.7 months. CONCLUSION: TACE of hepatic metastasis
      from uveal melanoma with fotemustine is well tolerated, and the survival rates in
      this study (mean, 28.7 months) are among the longest reported.

PMID- 23169736
TI  - Effectiveness, safety, and local progression after percutaneous laser ablation
      for hepatocellular carcinoma nodules up to 4 cm are not affected by tumor
      location.
AB  - OBJECTIVE: A high-risk location--defined as the tumor margin being less than 5 mm
      from large vessels or vital structures--represents a well-known limitation and
      contraindication for radiofrequency ablation of hepatocellular carcinoma (HCC)
      nodules. The aim of this study was to verify whether HCC nodule location
      negatively affected the outcome of percutaneous laser ablation in terms of its
      primary effectiveness, safety, and ability to prevent local tumor progression.
      MATERIALS AND METHODS: The medical records and radiologic examinations of 164
      cirrhotic patients (90 men, 74 women; mean age +/- SD, 68.6 +/- 8.3 years) with
      182 HCC nodules 4 cm or smaller (mean diameter +/- SD, 2.7 +/- 0.78 cm) that had
      been treated by laser ablation between 1996 and 2008 were retrospectively
      analyzed. One hundred six patients had 116 nodules in high-risk sites (high-risk
      group), whereas 58 patients had 66 tumors located elsewhere (standard-risk
      group). RESULTS: The overall median follow-up was 81 months (range, 6-144
      months). The initial complete ablation rate per nodule did not significantly
      differ between the high-risk group and the standard-risk group (92.2% vs 95.5%,
      respectively; p = 0.2711). Rates of major complications (high-risk group vs
      standard-risk group, 1.9% [including one death] vs 0%) and minor complications
      (5.6% vs 1.0%) were not statistically different between the two groups. Only side
      effects were recorded significantly more often in high-risk patients than in
      standard-risk patients (31.5% vs 19.8%; p = 0.049). There was no significant
      difference in either cumulative incidence of local tumor progression (p = 0.499)
      or local tumor progression-free survival (p = 0.499, log rank test) between the
      high-risk group and the standard-risk group. CONCLUSION: When laser ablation is
      used to treat small HCC nodules, tumor location does not have a significant
      negative impact on the technique's primary effectiveness or safety or on its
      ability to achieve local control of disease.

PMID- 23169737
TI  - Radiation dose and image quality at high-pitch CT angiography of the aorta:
      intraindividual and interindividual comparisons with conventional CT angiography.
AB  - OBJECTIVE: The objective of our study was to evaluate radiation dose and
      quantitative image quality parameters at high-pitch CT angiography (CTA) of the
      aorta compared with conventional CTA. MATERIALS AND METHODS: We studied the
      examinations of 110 patients (65 men and 45 women; mean age +/- SD, 64 +/- 15
      years) who had undergone CTA of the entire aorta on a second-generation dual
      source CT system; 50 examinations were performed in high-pitch mode. The mean
      arterial attenuation, signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR),
      and figure of merit (FOM) were calculated for the high-pitch CTA and conventional
      CTA groups. Radiation exposures were compared. RESULTS: All studies were
      considered of diagnostic quality. At high-pitch CTA, the mean tube voltage and
      tube current-exposure time product were 118 +/- 7 kV (SD) and 197 +/- 78 mAs
      compared with 120 +/- 1 kV and 258 +/- 78 mAs, respectively, at conventional CTA
      (p < 0.05). The mean volume CT dose index, dose-length product, and effective
      dose were 8.1 +/- 2.4 mGy, 561.1 +/- 178.6 mGy * cm, and 9.6 +/- 3.0 mSv at high
      pitch CTA and 18.3 +/- 7.7 mGy, 1162.6 +/- 480.1 mGy * cm, and 19.8 +/- 8.2 mSv
      at conventional CTA (p < 0.001). Attenuation was similar for both protocols,
      whereas significantly less contrast medium was injected for high-pitch CTA than
      for standard-pitch CTA (87.3 +/- 16 mL vs 97.9 +/- 16 mL, respectively; p <
      0.01). The SNR and CNR were significantly lower in the high-pitch CTA
      examinations (p < 0.01), whereas the FOM was nonsignificantly higher. Twenty
      patients underwent both high-pitch CTA and conventional CTA, with a 45% reduction
      in radiation dose (p < 0.001). CONCLUSION: High-pitch CTA of the aorta yields 45
      50% reduction of radiation exposure as well as contrast medium savings with
      maintained vessel attenuation.

PMID- 23169738
TI  - The value of pelvic MRI in the diagnosis of posterior cul-de-sac obliteration in
      cases of deep pelvic endometriosis.
AB  - OBJECTIVE: The objective of our study was to define relevant MRI signs allowing
      preoperative diagnosis of posterior cul-de-sac obliteration in patients with deep
      pelvic endometriosis. MATERIALS AND METHODS: This retrospective study included
      patients who underwent pelvic MRI completed by a laparoscopic examination. Three
      radiologists performed the MRI review blinded and recorded the following signs:
      sign 1, retroflexed uterus; sign 2, retrouterine mass; sign 3, displacement of
      intraperitoneal fluid; sign 4, elevation of the fornix; and sign 5, adherence of
      bowel loops. Laparoscopic results provided the criterion standard for diagnosis
      of posterior cul-de-sac obliteration. The performance of MRI was evaluated by
      calculating the average sensitivity, specificity, positive predictive value,
      negative predictive value, and accuracy of MRI results of the two more
      experienced radiologists for each sign and for combinations of signs.
      Interobserver agreement for each sign and impression for posterior cul-de-sac
      obliteration were calculated for all radiologists. RESULTS: Sixty-three patients
      were included in the study. Posterior cul-de-sac obliteration was diagnosed in 43
      patients at laparoscopy. The mean sensitivity, specificity, and accuracy of each
      sign and impression of posterior cul-de-sac obliteration were, respectively, as
      follows: sign 1, 24.4%, 77.5%, 41.3%; sign 2, 97.1%, 83.7%, 92.8%; sign 3, 95.0%,
      88.7%, 93.1%; sign 4, 30.2%, 97.5%, 51.6%; sign 5, 83.7%, 91.2%, 86.1%; and
      impression of posterior cul-de-sac obliteration, 91.9%, 91.2%, 91.7%.
      Interobserver concordance varied from 0.26 to 0.81 with best results obtained
      with the combination of signs 2, 3, and 5. Best concordances for junior
      radiologist evaluations were obtained with assessment of sign 3. CONCLUSION: MRI
      allows posterior cul-de-sac obliteration diagnosis. Pelvic fluid displacement may
      be the sign with greatest utility when considering both diagnostic accuracy and
      interobserver agreement.

PMID- 23169740
TI  - Confidentiality: an essential element of professionalism.

PMID- 23169739
TI  - Focal renal lesions in pediatric patients.

PMID- 23169741
TI  - CT of splenosis: patterns and pitfalls.
AB  - OBJECTIVE: After traumatic splenic injury or splenectomy, small isolated spleens
      may develop. These implants are not limited to the left upper quadrant, and
      splenosis in other locations can mimic other pathologic entities. This pictorial
      essay presents the range of appearances of intraabdominal and pelvic splenosis.
      CONCLUSION: Radiologists can suggest or establish the correct diagnosis of
      splenosis in the appropriate clinical setting, particularly in less typical
      cases, to avert unnecessary tissue sampling.

PMID- 23169742
TI  - Imaging features of primary and secondary adult rhabdomyosarcoma.
AB  - OBJECTIVE: Rhabdomyosarcomas are rare and aggressive soft-tissue sarcomas in
      adults. The purpose of this article is to describe the imaging features of
      primary and secondary adult rhabdomyosarcomas utilizing MRI, CT, and (18)F-FDG
      PET/CT. CONCLUSION: MRI is the imaging technique of choice for the evaluation of
      primary rhabdomyosarcoma involving most body sites (extremity, pelvis, head, and
      neck), with the added advantages of diffusion-weighted imaging and whole-body MRI
      for staging. CT and FDG PET/CT play major roles in the evaluation of metastatic
      disease. Because the imaging features of adult rhabdomyosarcoma are nonspecific,
      other parameters, such as clinical findings, age, site, lymphadenopathy, and
      metastatic disease, should be combined to narrow the differential diagnosis.

PMID- 23169743
TI  - Software Aids for radiologists: Part 1, Useful Photoshop skills.
AB  - OBJECTIVE: The purpose of this review is to describe the use of several essential
      techniques and tools in Adobe Photoshop image-editing software. The techniques
      shown expand on those previously described in the radiologic literature.
      CONCLUSION: Radiologists, especially those with minimal experience with image
      editing software, can quickly apply a few essential Photoshop tools to minimize
      the frustration that can result from attempting to navigate a complex user
      interface.

PMID- 23169744
TI  - Software Aids for radiologists: Part 2, Essential apps for handheld devices.
AB  - OBJECTIVE: The purpose of this review is to summarize applications (apps) for
      hand-held computing devices that can be essential aids to radiologists.
      CONCLUSION: Numerous apps are relevant to radiologists. Although the author
      prefers Apple iPad and iPhone apps, similar Android apps fill many of the same
      software niches.

PMID- 23169745
TI  - Sonographic evaluation of subclinical entheseal involvement in patients with
      Behcet disease.
AB  - OBJECTIVE: The aim of the current study was to determine the prevalence of
      subclinical entheseal involvement in patients with Behcet disease via ultrasound
      using a newly developed method, the Madrid sonography enthesitis index. SUBJECTS
      AND METHODS: The study was conducted with 36 patients with Behcet disease and 46
      healthy sex- and age-matched control subjects. All patients with Behcet disease
      who had no clinical evidence of arthritis or enthesitis underwent an ultrasound
      examination. All sonographic findings were identified according to the Madrid
      sonography enthesitis index. Madrid sonography enthesitis index values of
      patients and control subjects were compared by Student t test and Mann-Whitney U
      test. Validity was analyzed by receiver operating characteristic curve. RESULTS:
      Total enthesitis score was 12.16 +/- 6.16 among patients with Behcet disease and
      2.06 +/- 2.18 among healthy control subjects (p < 0.001). The receiver operating
      characteristic curve established an ultrasound score greater than 4.5 in the
      Behcet disease group as the best cut-off point differentiating case subjects from
      control subjects. This cutoff was exceeded by 88.8% of the patients with Behcet
      disease. When the Madrid sonography enthesitis index score in each affected
      enthesis was evaluated, patients with Behcet disease had significantly higher
      scores than did control subjects when all entheseal sites were compared (all p
      values < 0.05). CONCLUSION: This is the first study to our knowledge to show
      significant subclinical enthesopathy of the triceps tendon enthesis in patients
      with Behcet disease who had no arthritic involvement. These data suggest that the
      Madrid sonography enthesitis index scoring system for sonographic detection of
      enthesopathy should be incorporated into the clinical protocol for evaluating
      patients with Behcet disease in routine clinical practice.

PMID- 23169746
TI  - Characterization of synovial sarcoma calcification.
AB  - OBJECTIVE: The objective of our study was to characterize patterns of
      calcifications in synovial sarcoma. CONCLUSION: The presence of fine, stippled
      calcifications in a soft-tissue mass should raise suspicion for synovial sarcoma.
      These calcifications can coalesce to a deposit that mimics hydroxyapatite
      deposition disease or soft-tissue osteosarcoma. Spicules of calcification were a
      less common finding in our series; the appearance of spicules in synovial
      sarcomas overlaps with that of other soft-tissue sarcomas such as soft-tissue
      osteosarcoma and liposarcoma.

PMID- 23169748
TI  - Neonatal hypoxic-ischemic injury: sonography and dynamic color Doppler sonography
      perfusion of the brain and abdomen with pathologic correlation.
AB  - OBJECTIVE: The purpose of this article is to describe the role of cerebral and
      abdominal sonography with color Doppler sonography, including assessment of
      multiorgan tissue perfusion, in neonates with hypoxic-ischemic injury.
      CONCLUSION: Bedside sonography and color Doppler sonography of the brain and
      abdominal organs can provide reliable and comprehensive information in
      asphyxiated neonates with hypoxic-ischemic injury. This article, which includes
      pathologic correlation, illustrates the major sonographic findings in this
      critical population.

PMID- 23169747
TI  - STIR sequence with increased receiver bandwidth of the inversion pulse for
      reduction of metallic artifacts.
AB  - OBJECTIVE: The purpose of this study was to evaluate a STIR sequence with an
      optimized inversion pulse that entails use of increased receiver bandwidth for
      metal artifact reduction. CONCLUSION: Image distortion, artifacts, insufficient
      fat suppression, and detection of relevant findings improved with the STIR
      optimized inversion pulse, which was associated with significant artifact
      reduction.

PMID- 23169749
TI  - Complication rate of ultrasound-guided percutaneous cholecystostomy in patients
      with coagulopathy.
AB  - OBJECTIVE: The purpose of this article is to compare the complication rate for
      ultrasound-guided percutaneous cholecystostomy in patients with coagulopathy to
      the rate in patients with normal coagulation. MATERIALS AND METHODS: We performed
      a database search for patients who underwent ultrasound-guided percutaneous
      cholecystostomy from January 2000 through December 2010. Patients were divided
      into those with normal coagulation and those with coagulopathy, as documented by
      abnormal laboratory values (international normalized ratio >= 1.5 and platelet
      count <= 50 * 10(9)/L) or history of anticoagulant medication in the preceding 5
      days. Medical records were reviewed, and complication rates and subsequent
      treatment was recorded. Statistical analysis was performed using the Fisher exact
      and chi-square tests. RESULTS: Two hundred forty-two patients underwent
      ultrasound-guided percutaneous cholecystostomy (132 men and 110 women; mean [+/-
      SD] age, 73.9 +/- 15.9 years; range, 22-104 years). One hundred thirty-two
      patients were coagulopathic and 110 had normal coagulation. Major complications
      related to ultrasound-guided percutaneous cholecystostomy were rare (4/242 cases
      [1.7%]) and included hemorrhage requiring transfusion (n = 1), death directly
      related to the procedure (n = 1), sepsis related to the procedure (n = 1), and
      abscess or biloma formation (n = 1). All of these occurred in the group with
      normal coagulation. Fourteen additional deaths (5.8%) that occurred within 30
      days of the procedure were related to comorbidities. Minor catheter-related
      complications (15/242 [6.2%]) were due to catheter dislodgement (n = 11 [4.5%]),
      failure of placement (n = 1 [0.4%]), and hemorrhage not requiring transfusion (n
      = 3 [1.2%]). Two of the minor hemorrhagic complications were seen in the
      coagulopathic group and one in the normal coagulation group (p = 0.599).
      CONCLUSION: There is no difference in the complication rate for ultrasound-guided
      percutaneous cholecystostomy in patients who are coagulopathic compared with
      those who have normal coagulation.

PMID- 23169751
TI  - Gamma camera breast imaging lexicon.
AB  - OBJECTIVE: The standardized terminology and reporting structure of the BI-RADS
      for mammography, ultrasound, and MRI findings facilitates patient management. To
      date, no such terminology has been available for gamma camera breast imaging. We
      present an illustrated lexicon including description of background uptake, mass
      and nonmass uptake, lesion intensity, associated findings, and review of common
      artifacts. CONCLUSION: This proposed lexicon should facilitate standardized
      interpretation, communication of results, and outcomes monitoring of examinations
      using dedicated devices for gamma camera breast imaging.

PMID- 23169750
TI  - Afferent loop syndrome: treatment by means of the placement of dual stents.
AB  - OBJECTIVE: The purpose of this article is to assess the technical feasibility and
      clinical effectiveness of the placement of partially covered self-expandable dual
      stents in patients with afferent loop syndrome. MATERIALS AND METHODS: Data from
      13 consecutive patients who had undergone partially covered dual stent placement
      for afferent loop syndrome after various types of surgery were retrospectively
      analyzed. Nine patients underwent stent placement via the percutaneous
      transhepatic biliary drainage tract, and four patients underwent placement via
      the peroral route. A total of 16 stents were used in this study (i.e., 15 dual
      stents and one fully covered esophageal stent). RESULTS: The route of stent
      insertion was determined on the basis of each patient's general condition, the
      site of obstruction, anatomic variations, and associated symptoms. Stent
      placement was technically successful in all patients. After stent placement, 12
      of 13 patients experienced normalization of their abnormal biliary laboratory
      findings and decompression of the dilated bowel loop, whereas the remaining
      patient showed no change. This patient had to undergo the additional treatment of
      surgical jejunojejunostomy. No procedure-related complications occurred in any
      patients enrolled in this study. CONCLUSION: Placement of partially covered dual
      stents appears to be a promising technique that may offer successful palliation
      for patients who develop afferent loop syndrome after various types of surgery.

PMID- 23169752
TI  - Radiologists versus perinatologists when interpreting prenatal ultrasound
      examinations.

PMID- 23169753
TI  - I've been sued for malpractice: should I hire my own attorney in addition to the
      one assigned to me by my insurance carrier?

PMID- 23169754
TI  - Water-soluble contrast agents in small bowel obstruction: a useful discriminator.

PMID- 23169755
TI  - Understanding the mathematics involved in calculating apparent diffusion
      coefficient maps.

PMID- 23169756
TI  - Stuart S. Sagel: master radiologist and educator.

PMID- 23169757
TI  - Hypersociability in the behavioral phenotype of 17q21.31 microdeletion syndrome.
AB  - The 17q21.31 microdeletion syndrome with its characteristic features including
      developmental delay, moderate intellectual disability, facial dysmorphisms, and
      anomalies of the brain and multiple organ systems was recently described. As to
      its behavioral profile, scarce data from clinical observations have suggested a
      remarkably amiable, friendly disposition, to some extent comparable to that
      observed in Angelman and Williams syndromes. The present study focuses on the
      various aspects of neurocognitive functioning, particularly social cognition, in
      patients with 17q21.31 microdeletion syndrome. Neuropsychological assessment was
      performed in three out of the four known Dutch patients with a genetically proven
      17q21.31 microdeletion syndrome. Apart from developmental age, cognition and
      social-emotional functioning was extensively assessed. In addition, data of three
      intellectually disabled physically healthy reference subjects, recruited from a
      small outpatient sample, were included. The general cognitive profile of all
      subjects was in accordance with their lowered intellectual capacities, albeit
      that in patients with the 17q21.31 microdeletion, a relatively strong memory for
      social-contextual information was found. Basic emotion perception was intact, but
      patients with the 17q21.31 microdeletion syndrome showed less social fear and
      more approaching behavior. Interestingly, alexithymic traits, that is marked
      difficulties in the recognition and expression of emotions, were more prevalent
      in reference subjects. Despite the methodological limitations characteristic for
      research in people with intellectual disabilities, with a neuropsychological
      assessment strategy, in three patients with 17q21.31 microdeletion syndrome,
      preliminary evidence for hypersocial behavior with a high level of frustration
      tolerance was found that may be implicated in its behavioral phenotype.

PMID- 23169758
TI  - Computational modelling of the right ventricle in repaired tetralogy of Fallot:
      can it provide insight into patient treatment?
AB  - AIMS: Pulmonary regurgitation (PR) causes progressive right ventricle (RV)
      dilatation and dysfunction in repaired tetralogy of Fallot (rToF). Declining RV
      function is often insidious and the timing of pulmonary valve replacement remains
      under debate. Quantifying the pathophysiology of adverse RV remodelling due to
      worsening PR may help in defining the best timing for pulmonary valve
      replacement. Our aim was to identify whether complex three-dimensional (3D)
      deformations of RV shape, as assessed with computer modelling, could constitute
      an anatomical biomarker that correlated with clinical parameters in rToF
      patients. METHODS AND RESULTS: We selected 38 rToF patients (aged 10-30 years)
      who had complete data sets and had not undergone PVR from a population of 314
      consecutive patients recruited in a collaborative study of four hospitals. All
      patients underwent cardiovascular magnetic resonance (CMR) imaging: PR and RV end
      diastolic volumes were measured. An unbiased shape analysis framework was used
      with principal component analysis and linear regression to correlate shape with
      indexed PR volume. Regurgitation severity was significantly associated with RV
      dilatation (P = 0.01) and associated with bulging of the outflow tract (P = 0.07)
      and a dilatation of the apex (P = 0.08). CONCLUSION: In this study, we related RV
      shape at end-diastole to clinical metrics of PR in rToF patients. By considering
      the entire 3D shape, we identified a link between PR and RV dilatation, outflow
      tract bulging, and apical dilatation. Our study constitutes a first attempt to
      correlate 3D RV shape with clinical metrics in rToF, opening new ways to better
      quantify 3D RV change in rToF.

PMID- 23169759
TI  - Coronary flow reserve as a link between diastolic and systolic function and
      exercise capacity in heart failure.
AB  - AIMS: In heart failure, a reduced exercise capacity is the prevailing symptom and
      an important prognostic marker of future outcome. The purpose of the study was to
      assess the relation of coronary flow reserve (CFR) to diastolic and systolic
      function in heart failure and to determine which are the limiting factors for
      exercise capacity. METHODS AND RESULTS: Forty-seven patients with left
      ventricular ejection fraction (LVEF) <35 [median LVEF 31 (inter-quartile range 26
      34)] underwent cardiorespiratory exercise test with measurement of VO2 peak, a
      dual X-ray absorptiometry scan for body composition, and a full echocardiography
      with measurement of LVEF using the biplane Simpson model, mitral inflow
      velocities, and pulsed wave tissue Doppler. Peak coronary flow velocity (CFV) was
      measured in the LAD, using pulsed-wave Doppler. CFR was calculated as the ratio
      between peak CFV at rest and during 2 min of adenosine stress. Fat-free-mass
      adjusted VO2 peak correlated significantly with CFR (r = 0.48, P = 0.002), E/e'
      (r = -0.35, P = 0.02), and s' (r = 0.45, P = 0.001) but not with LVEF (r = 0.23,
      P = 0.11). CFR correlated significantly with E/e' (r = -0.46, P = 0.003) and s'
      (r = 0.36, P = 0.02), but not with LVEF (r = 0.18, P = 0.26). When adjusting for
      CFR in a multivariable linear model, s' but not E/e' remained independently
      associated with VO2 peak. CONCLUSION: In this group of heart failure patients,
      VO2 peak was correlated with CFR, E/e', and s' but not with traditional measures
      of systolic function. CFR remained associated with VO2 peak independently of
      diastolic and systolic function and is likely to be a limiting factor in
      functional capacity of heart failure patients.

PMID- 23169760
TI  - Effects of siRNA targeting c-Myc and VEGF on human colorectal cancer Volo cells.
AB  - c-Myc and vascular endothelial growth factor (VEGF) genes are frequently
      deregulated and overexpressed in this malignancy, and strategies designed to
      inhibit c-Myc and VEGF expression in cancer cells may have considerable
      therapeutic value. In the present study, we design and use short interfering RNA
      (siRNA) to inhibit c-Myc and VEGF expression in colorectal cancer Volo cells and
      validate their effects on cell proliferation, cell cycle, apoptosis, and cell
      metastasis. Upon transient transfection with plasmid-encoding siRNA, it was found
      that expression of c-Myc and VEGF was significantly downregulated in siRNA
      transfected cells and the downregulation of c-Myc and VEGF inhibited cell growth
      and induced apoptosis and metastasis of Volo cells. c-Myc and VEGF downregulation
      also increased cell population in the G0-G1 phase. In conclusion, the specific
      siRNA efficiently silenced the expression of c-Myc and VEGF, further suppressed
      the cell proliferation, triggered cell apoptosis, and inhibited cell invasiveness
      of colorectal cancer Volo cells.

PMID- 23169761
TI  - The behavioral phenotype in MECP2 duplication syndrome: a comparison with
      idiopathic autism.
AB  - Alterations in the X-linked gene MECP2 encoding the methyl-CpG-binding protein 2
      have been linked to autism spectrum disorders (ASDs). Most recently, data suggest
      that overexpression of MECP2 may be related to ASD. To better characterize the
      relevance of MECP2 overexpression to ASD-related behaviors, we compared the core
      symptoms of ASD in MECP2 duplication syndrome to nonverbal mental age-matched
      boys with idiopathic ASD. Within the MECP2 duplication group, we further
      delineated aspects of the behavioral phenotype and also examined how duplication
      size and gene content corresponded to clinical severity. We compared ten males
      with MECP2 duplication syndrome (ages 3-10) with a chronological and mental age
      matched sample of nine nonverbal males with idiopathic ASD. Our results indicate
      that boys with MECP2 duplication syndrome share the core behavioral features of
      ASD (e.g. social affect, restricted/repetitive behaviors). Direct comparisons of
      ASD profiles revealed that a majority of boys with MECP2 duplication syndrome are
      similar to idiopathic ASD; they have impairments in social affect (albeit to a
      lesser degree than idiopathic ASD) and similar severity in restricted/repetitive
      behaviors. Nonverbal mental age did not correlate with severity of social
      impairment or repetitive behaviors. Within the MECP2 duplication group,
      breakpoint size does not predict differences in clinical severity. In addition to
      social withdrawal and stereotyped behaviors, we also found that hyposensitivity
      to pain/temperature are part of the behavioral phenotype of MECP2 duplication
      syndrome. Our results illustrate that overexpression/increased dosage of MECP2 is
      related to core features of ASD.

PMID- 23169762
TI  - Gold(III)- versus gold(I)-induced cyclization: synthesis of six-membered
      mesoionic carbene and acyclic (aryl)(heteroaryl) carbene complexes.
AB  - The golden state: selective 5-exo- and 6-endo-cyclizations of an alkynyl
      benzothioamide have been achieved. The selectivity is controlled by the oxidation
      state of the gold precursor (+I or +III), yielding two new types of carbene
      ligand: an (aryl)(heteroaryl)carbene and a six-membered mesoionic carbene.
      Mes=2,4,6-trimethylphenyl.

PMID- 23169763
TI  - Developmental and behavioral characteristics of individuals with Pallister
      Killian syndrome.
AB  - Pallister-Killian syndrome is a sporadic disorder caused by the presence of
      mosaic tetrasomy of the short arms of chromosome 12. Case reports of children
      with Pallister-Killian syndrome have described a range of developmental and
      behavioral outcomes, but no systematic studies of these outcomes exist. The
      objective of this study was to describe developmental and behavioral
      characteristics of individuals with Pallister-Killian syndrome participating in a
      national meeting of families and their affected children. Sixteen individuals
      with Pallister-Killian syndrome, ages 16 months to 19 years, were studied using
      questionnaires and direct interview. Among the 16 patients enrolled in the study,
      3 probands were between 16 and 19 months, and had severe developmental delay.
      Among the rest of the 13 probands older than 24 months, 11 children had a
      developmental level of less than 8 months age equivalent. They were non
      ambulatory, non-verbal, and passive, requiring extensive assistance in daily
      living. There were two higher functioning children who were ambulatory, and
      verbal. One of these children met criteria for Autism on the Autism Diagnostic
      Interview-Revised. Thus, although most individuals with Pallister-Killian
      syndrome studied showed profound intellectual disability and sensory impairments,
      individuals with Pallister-Killian syndrome can have mild to moderate
      intellectual disability. Therefore, in individuals with physical examination
      findings of Pallister-Killian syndrome, formal diagnostic testing should be
      considered, even in individuals with mild to moderate intellectual disability.
      Further studies will be needed to determine if these higher functioning children
      with Pallister-Killian syndrome are at increased risk for autism.

PMID- 23169764
TI  - Is today's marijuana more potent simply because it's fresher?
AB  - The average potency of illicit marijuana in the USA has increased substantially
      over the past four decades, and observers have suggested a number of likely
      reasons for this. One set of hypotheses points to a market that has evolved from
      foreign to domestic sources of supply, and to continuing advances in
      sophisticated cultivation techniques. Another set of hypotheses points to testing
      artifacts related to changes in the sampling, handling, and testing of illicit
      marijuana. The current study uses data from the federally sponsored Potency
      Monitoring Program, which performs ongoing forensic analysis of seized marijuana
      samples, to assess the extent to which the observed increase in cannabis potency
      in the USA between 1970 and 2010 is a function of genuine shifts in illicit
      marijuana markets or testing artifacts related to changes in the quality of
      seized marijuana. The study finds, after adjusting for marijuana quality, that
      the apparent 10.5 factor increase in mean reported THC% between the 1970s and the
      2000s is instead on the order of a six- to seven-fold increase. By this
      accounting, then, the reported long-term rise in potency is roughly 57-67% as
      great when the quality of the tested marijuana is taken into account. This
      study's findings, therefore, caution against the uncritical use of potency
      monitoring data and highlight the importance of assessing potency measurement
      reliability and addressing data quality issues in future policy analytic
      research.

PMID- 23169765
TI  - Carbamate protection of AChE against inhibition by agricultural chemicals.
AB  - The carbamate pyridostigmine bromide has been used as a pretreatment to protect
      individuals from the nerve agent soman. Previous research showed that
      pyridostigmine significantly protected human muscle acetylcholinesterase in vitro
      from soman and bovine red blood cell acetylcholinesterase from some
      organophosphorous pesticides. Research presented here demonstrates that
      pretreatment with other carbamates also protects acetylcholinesterase from
      inhibition by the pesticides chlorpyrifos-oxon and diazinon-oxon, but not from
      malaoxon.

PMID- 23169766
TI  - Stereoselective total syntheses of (-)-flueggine A and (+)-virosaine B.
AB  - Convergent approach: the total syntheses of (-)-flueggine A and (+)-virosaine B
      have been accomplished in a concise and convergent manner. Key steps in these
      approaches were relay ring-closing metathesis reactions for rapid construction of
      the key intermediates, and 1,3-dipolar cycloaddition reactions for the formation
      of the natural products.

PMID- 23169767
TI  - Novel clinical manifestations in Pallister-Killian syndrome: comprehensive
      evaluation of 59 affected individuals and review of previously reported cases.
AB  - Pallister-Killian syndrome is a rare, multi-system developmental diagnosis
      typically caused by tetrasomy of chromosome 12p that exhibits tissue-limited
      mosaicism. The spectrum of clinical manifestations in Pallister-Killian syndrome
      is wide and includes craniofacial anomalies, clefts, ophthalmologic, audiologic,
      cardiac, musculoskeletal, diaphragmatic, gastrointestinal, genitourinary, and
      cutaneous anomalies in association with intellectual disability and seizures.
      Growth parameters are often normal to elevated at birth with deceleration of
      growth postnatally. No formal estimate of the prevalence of Pallister-Killian
      syndrome has been made. Here, we report the clinical findings in 59 individuals
      with Pallister-Killian syndrome who were ascertained at Pallister-Killian
      syndrome Foundation family meetings held in the summers of 2006, 2008, 2009, and
      2010. In addition, the clinical findings of 152 cases reported in the medical
      literature were reviewed and compared to the cohort examined here. Several novel
      clinical characteristics were identified through detailed dysmorphology
      examinations of this cohort and reassertion of a mild developmental variant is
      described. This report expands the clinical manifestations of Pallister-Killian
      syndrome and highlights the variable expressivity of this diagnosis with
      important implications for diagnosis and counseling.

PMID- 23169768
TI  - Single-blind randomized controlled trial of surfactant vs hypertonic saline
      irrigation following endoscopic endonasal surgery.
AB  - BACKGROUND: Recent discussion has revolved around formulations of irrigation in
      the postoperative functional endoscopic sinus surgery patient, specifically the
      efficacy of emulsion based nasal irrigations. METHODS: Forty adult candidates for
      endoscopic endonasal surgery with chronic rhinosinusitis (CRS) were prospectively
      randomized. The 22-item Sino-Nasal Outcome Test (SNOT-22) and 31-item
      Rhinosinusitis Outcome Measure (RSOM-31) quality of life assessments, as well as
      a phenyl ethyl alcohol (PEA) smell threshold test were obtained preoperatively
      and over 3 postoperative visits in a 4-month period. Repeated measures analyses
      and Fisher's exact tests were used to assess statistical differences. RESULTS: Of
      the 40 patients enrolled, 33, 32, and 26 patients were seen at postoperative
      visits 1, 2, and 3, respectively. The surfactant (S) and hypertonic saline (HS)
      irrigation groups both showed significant decreases in scores for both the SNOT
      22 and RSOM-31 over time (both p < 0.0001), but no difference was seen between
      the 2 groups (p = 0.09, p = 0.5). PEA thresholds showed overall improvement in
      both groups 3 to 4 months after surgery: 62% (8/13) of HS patients and 50% (6/12)
      of S patients, but did not differ between the groups (p = 0.3). The S group
      reported significantly more side effects (52% vs 6%, p = 0.002) and had more
      patients stop the solution (20% vs 0%) and fewer S patients finished the study
      compared to the HS group. CONCLUSION: There were no significant differences in
      overall subjective symptoms related to sinonasal disease between S and HS
      irrigation, but tolerability appeared to be an issue. More patients reported side
      effects with S irrigation, and 20% receiving S irrigation stopped the solution,
      compared to none receiving HS irrigation.

PMID- 23169769
TI  - Optimization of fluorescence assay of cellular manganese status for high
      throughput screening.
AB  - The advent of high throughput screening (HTS) technology permits identification
      of compounds that influence various cellular phenotypes. However, screening for
      small molecule chemical modifiers of neurotoxicants has been limited by the
      scalability of existing phenotyping assays. Furthermore, the adaptation of
      existing cellular assays to HTS format requires substantial modification of
      experimental parameters and analysis methodology to meet the necessary
      statistical requirements. Here we describe the successful optimization of the
      Cellular Fura-2 Manganese Extraction Assay (CFMEA) for HTS. By optimizing
      cellular density, manganese (Mn) exposure conditions, and extraction parameters,
      the sensitivity and dynamic range of the fura-2 Mn response was enhanced to
      permit detection of positive and negative modulators of cellular manganese
      status. Finally, we quantify and report strategies to control sources of intra-
      and interplate variability by batch level and plate-geometric level analysis. Our
      goal is to enable HTS with the CFMEA to identify novel modulators of Mn
      transport.

PMID- 23169770
TI  - Cigarette smoking affects oxidative protein folding in endoplasmic reticulum by
      modifying protein disulfide isomerase.
AB  - The endoplasmic reticulum (ER) stress response (ERSR) and associated protein
      aggregation, is under investigation for its role in human diseases, including
      chronic obstructive pulmonary disease (COPD) where cigarette smoking (CS) is a
      risk factor for disease development. Our hypothesis states that CS-associated
      oxidative stress interferes with oxidative protein folding in the ER and elicits
      ERSR. We investigated ERSR induction following acute CS exposure and delineated
      mechanisms of CS-induced ERSR. Lung lysates from mice exposed or not to one
      cigarette were tested for activation of the ERSR. Up to 4-fold increase in
      phosphorylation of eIF2alpha and nuclear form of ATF6 was detected in CS-exposed
      animals. CS affected the formation of disulfide bonds through excessive
      posttranslational oxidation of protein disulfide isomerase (PDI). Increased
      amounts of complexes between PDI and its client proteins persisted in CS-exposed
      samples. BiP was not a constituent of these complexes, demonstrating the
      specificity of the early effects of CS exposure on ER. Disturbances in protein
      folding were accompanied by changes in the organization of ER network and ER exit
      sites. Our results provide evidence that ERSR is induced early in response to CS
      exposure and identifies the first known ER-resident target of CS PDI,
      demonstrating that CS affects oxidative protein folding.

PMID- 23169771
TI  - Novel role for ALCAM in lymphatic network formation and function.
AB  - Adhesion molecules play an important role in vascular biology because they
      mediate vascular stability, permeability, and leukocyte trafficking to and from
      tissues. Performing microarray analyses, we have recently identified activated
      leukocyte cell adhesion molecule (ALCAM) as an inflammation-induced gene in
      lymphatic endothelial cells (LECs). ALCAM belongs to the immunoglobulin
      superfamily and engages in homophilic as well as heterophilic interactions. In
      this study, we found ALCAM to be expressed at the protein level in human and
      murine lymphatic and blood vascular endothelial cells in vitro and in the
      vasculature of human and murine tissues in vivo. Functional in vitro experiments
      revealed that ALCAM mediates adhesive interactions, migration, and tube formation
      in LECs, suggesting a role for ALCAM in lymphatic vessel (LV) stability and in
      lymphangiogenesis. Furthermore, ALCAM supported dendritic cell (DC) adhesion to
      lymphatic endothelium. In agreement with these findings, experiments performed in
      ALCAM mice detected reduced LEC numbers in various tissues and defects in the
      formation of an organized LV network. Moreover, DC migration from lung to
      draining lymph nodes was compromised in ALCAM mice. Collectively, our data reveal
      a novel role for ALCAM in stabilizing LEC-LEC interactions and in the
      organization and function of the LV network.

PMID- 23169772
TI  - Predicting the structure of cyclic lipopeptides by bioinformatics: structure
      revision of arthrofactin.
AB  - Arthrofactin, a bioactive cyclic lipopeptide from Pseudomonas sp. MIS38, was
      reinvestigated for its structural and stereochemical features due to
      discrepancies between the genetics-based sequence prediction and the currently
      suggested structure. The structure of arthrofactin and its derivatives was
      reassigned on the basis of chiral HPLC analysis and extensive NMR and MS
      experiments. Furthermore, derivatives of arthrofactin were discovered.

PMID- 23169773
TI  - Utility of SNP arrays in detecting, quantifying, and determining meiotic origin
      of tetrasomy 12p in blood from individuals with Pallister-Killian syndrome.
AB  - Identification of the isochromosome 12p (i(12p)) associated with Pallister
      Killian syndrome is complicated by the low frequency of this supernumerary
      chromosome in PHA stimulated peripheral blood lymphocytes, and frequently
      requires cytogenetic analysis of fibroblast cells. Recently, it has been shown
      that array CGH techniques are able to detect tetrasomy 12p in peripheral blood,
      even when not identified by traditional cytogenetic techniques. We studied 15
      patients with a previous cytogenetic and clinical diagnosis of Pallister-Killian
      syndrome using genome-wide SNP arrays to investigate the ability of this platform
      to identify the i(12p) in blood and tissue. Array analysis verified tetrasomy 12p
      in all samples from fibroblasts, but was only able to detect it in 46% of blood
      samples. The genotyping information available from the SNP arrays allowed for the
      detection of as low as 5% mosaicism, as well as suggesting a Meiosis II origin
      for the isochromosome in the majority of patients. Analysis of the percentage of
      abnormal cells with patient age at time of study suggests that the frequency of
      the i(12p) decreased with age in blood, but not in fibroblasts. These highlight
      the power of SNP arrays in detecting and characterizing the isochromosome 12p in
      Pallister-Killian syndrome as well as underscoring the important utility of
      traditional cytogenetic techniques.

PMID- 23169774
TI  - A decade whizzes by.

PMID- 23169775
TI  - Comparative study of regional homogeneity in schizophrenia and major depressive
      disorder.
AB  - Compelling evidence suggests that there is a considerable overlap in structural
      and functional alternation in the brain between different neuropsychiatric
      disorders. However, whether these overlaps are specific for schizophrenia has yet
      to be investigated. A total of 36 patients with paranoid schizophrenia, 43
      patients with major depressive disorder (MDD), and 44 healthy controls were
      recruited to undergo resting-state functional magnetic resonance imaging (rs
      fMRI) for analysis of regional homogeneity (ReHo). Twelve regions of interest
      (ROIs) in the frontal and temporal lobes were generated and one-way ANOVA was
      performed to test the ReHo differences within these ROIs between the above three
      groups. The ReHo values within ROIs were extracted to investigate whether a left
      right asymmetry existed in a mental disorder. One-way ANOVA showed significant
      differences in ReHo in the right superior frontal gyrus and left superior
      temporal gyrus; post hoc analysis revealed that schizophrenic patients had lower
      ReHo in the left superior temporal gyrus than either control subjects or patients
      with MDD. Increased ReHo was observed in the right superior frontal gyrus in
      schizophrenic patients compared with control subjects, and a left-less-than-right
      asymmetry was also found in this region in schizophrenic patients. The above
      alterations in ReHo were not affected by age and genders. Our study suggests that
      the altered ReHo in the superior frontal and temporal gyrus may be specific for
      schizophrenia rather than MDD. A left-less-than-right asymmetry activation
      pattern may exist in the resting-state superior frontal gyrus in schizophrenia.
      This finding would be helpful for better understanding the pathological
      mechanisms of schizophrenia.

PMID- 23169777
TI  - Role of SOX17 in hematopoietic development from human embryonic stem cells.
AB  - To search for genes that promote hematopoietic development from human embryonic
      stem cells (hESCs) and induced pluripotent stem cells (iPSCs), we overexpressed
      several known hematopoietic regulator genes in hESC/iPSC-derived CD34(+)CD43(-)
      endothelial cells (ECs) enriched in hemogenic endothelium (HE). Among the genes
      tested, only Sox17, a gene encoding a transcription factor of the SOX family,
      promoted cell growth and supported expansion of CD34(+)CD43(+)CD45(-/low) cells
      expressing the HE marker VE-cadherin. SOX17 was expressed at high levels in
      CD34(+)CD43(-) ECs compared with low levels in CD34(+)CD43(+)CD45(-) pre
      hematopoietic progenitor cells (pre-HPCs) and CD34(+)CD43(+)CD45(+) HPCs. Sox17
      overexpressing cells formed semiadherent cell aggregates and generated few
      hematopoietic progenies. However, they retained hemogenic potential and gave rise
      to hematopoietic progenies on inactivation of Sox17. Global gene-expression
      analyses revealed that the CD34(+)CD43(+)CD45(-/low) cells expanded on
      overexpression of Sox17 are HE-like cells developmentally placed between ECs and
      pre-HPCs. Sox17 overexpression also reprogrammed both pre-HPCs and HPCs into HE
      like cells. Genome-wide mapping of Sox17-binding sites revealed that Sox17
      activates the transcription of key regulator genes for vasculogenesis,
      hematopoiesis, and erythrocyte differentiation directly. Depletion of SOX17 in
      CD34(+)CD43(-) ECs severely compromised their hemogenic activity. These findings
      suggest that SOX17 plays a key role in priming hemogenic potential in ECs,
      thereby regulating hematopoietic development from hESCs/iPSCs.

PMID- 23169779
TI  - Clinical drug resistance linked to interconvertible phenotypic and functional
      states of tumor-propagating cells in multiple myeloma.
AB  - The phenotype and function of cells enriched in tumor-propagating activity and
      their relationship to the phenotypic architecture in multiple myeloma (MM) are
      controversial. Here, in a cohort of 30 patients, we show that MM composes 4
      hierarchically organized, clonally related subpopulations, which, although
      phenotypically distinct, share the same oncogenic chromosomal abnormalities as
      well as immunoglobulin heavy chain complementarity region 3 area sequence.
      Assessed in xenograft assays, myeloma-propagating activity is the exclusive
      property of a population characterized by its ability for bidirectional
      transition between the dominant CD19(-)CD138(+) plasma cell (PC) and a low
      frequency CD19(-)CD138(-) subpopulation (termed Pre-PC); in addition, Pre-PCs are
      more quiescent and unlike PCs, are primarily localized at extramedullary sites.
      As shown by gene expression profiling, compared with PCs, Pre-PCs are enriched in
      epigenetic regulators, suggesting that epigenetic plasticity underpins the
      phenotypic diversification of myeloma-propagating cells. Prospective assessment
      in paired, pretreatment, and posttreatment bone marrow samples shows that Pre-PCs
      are up to 300-fold more drug-resistant than PCs. Thus, clinical drug resistance
      in MM is linked to reversible, bidirectional phenotypic transition of myeloma
      propagating cells. These novel biologic insights have important clinical
      implications in relation to assessment of minimal residual disease and
      development of alternative therapeutic strategies in MM.

PMID- 23169780
TI  - Human ESC-derived hemogenic endothelial cells undergo distinct waves of
      endothelial to hematopoietic transition.
AB  - Several studies have demonstrated that hematopoietic cells originate from
      endotheliumin early development; however, the phenotypic progression of
      progenitor cells during human embryonic hemogenesis is not well described. Here,
      we define the developmental hierarchy among intermediate populations of
      hematopoietic progenitor cells (HPCs) derived from human embryonic stem cells
      (hESCs). We genetically modified hESCs to specifically demarcate acquisition of
      vascular (VE-cadherin) and hematopoietic (CD41a) cell fate and used this dual
      reporting transgenic hESC line to observe endothelial to hematopoietic transition
      by real-time confocal microscopy. Live imaging and clonal analyses revealed a
      temporal bias in commitment of HPCs that recapitulates discrete waves of lineage
      differentiation noted during mammalian hemogenesis. Specifically, HPCs isolated
      at later time points showed reduced capacity to form erythroid/ megakaryocytic
      cells and exhibited a tendency toward myeloid fate that was enabled by expression
      of the Notch ligand Dll4 on hESC-derived vascular feeder cells. These data
      provide a framework for defining HPC lineage potential, elucidate a molecular
      contribution from the vascular niche in promoting hematopoietic lineage
      progression, and distinguish unique subpopulations of hemogenic endothelium
      during hESC differentiation. KEY POINTS: Live imaging of endothelial to
      hematopoietic conversion identifies distinct subpopulations of hESC-derived
      hemogenic endothelium. Expression of the Notch ligand DII4 on vascular ECs drives
      induction of myeloid fate from hESC-derived hematopoietic progenitors.

PMID- 23169778
TI  - Safety and efficacy of eltrombopag for treatment of chronic immune
      thrombocytopenia: results of the long-term, open-label EXTEND study.
AB  - Patients with chronic immune thrombocytopenia may have bleeding resulting from
      low platelet counts. Eltrombopag increases and maintains hemostatic platelet
      counts; however, to date, outcome has been reported only for treatment lasting <=
      6 months. This interim analysis of the ongoing open-label EXTEND (Eltrombopag
      eXTENded Dosing) study evaluates the safety and efficacy of eltrombopag in 299
      patients treated up to 3 years. Splenectomized and nonsplenectomized patients
      achieved platelets >= 50 000/MUL at least once (80% and 88%, respectively).
      Platelets >= 50 000/MUL and 2 * baseline were maintained for a median of 73 of
      104 and 109 of 156 cumulative study weeks, respectively. Bleeding symptoms (World
      Health Organization Grades 1-4) decreased from 56% of patients at baseline to 20%
      at 2 years and 11% at 3 years. One hundred (33%) patients were receiving
      concomitant treatments at study entry, 69 of whom attempted to reduce them; 65%
      (45 of 69) had a sustained reduction or permanently stopped >= 1 concomitant
      treatment. Thirty-eight patients (13%) experienced >= 1 adverse events leading to
      study withdrawal, including patients meeting protocol-defined withdrawal criteria
      (11 [4%] thromboembolic events, 5 [2%] exceeding liver enzyme thresholds). No new
      or increased incidence of safety issues was identified. Long-term treatment with
      eltrombopag was generally safe, well tolerated, and effective in maintaining
      platelet counts in the desired range.

PMID- 23169781
TI  - A novel function for FOXP3 in humans: intrinsic regulation of conventional T
      cells.
AB  - The role of forkhead box P3 (FOXP3) is well-established in T-regulatory cells,
      but the function of transient FOXP3 expression in activated human conventional T
      (Tconv) cells is unknown. In the present study, we used 2 approaches to determine
      the role of FOXP3 in human Tconv cells. First, we obtained Tconv clones from a
      female subject who is hemizygous for a null mutation in FOXP3, allowing the
      comparison of autologous T-cell clones that do or do not express FOXP3. Second,
      we knocked down activation-induced FOXP3 in Tconv cells from healthy donors with
      small interfering RNAagainst FOXP3. We found that FOXP3-deficient Tconv cells
      proliferate more and produce more cytokines than wild-type Tconv cells and have
      differential expression of 274 genes. We also investigated the role of FOXP3 in
      Th1 and Th17 cells and found that the expression of activation-induced FOXP3 was
      higher and more sustained in Th17 cells compared with Th1 cells. Knocking down
      FOXP3 expression in Th17 cells significantly increased the production of IFN
      gamma and decreased the expression of CCR4, but had no effect on IL-17
      expression. These data reveal a novel function of FOXP3 in Tconv cells and
      suggest that expression of this protein is important in the function of multiple
      CD4(+) T-cell lineages.

PMID- 23169782
TI  - Overexpression of uridine diphospho glucuronosyltransferase 2B17 in high-risk
      chronic lymphocytic leukemia.
AB  - Uridine diphospho glucuronosyltransferase 2B17 (UGT2B17) glucuronidates androgens
      and xenobiotics including certain drugs. The UGT2B17 gene shows a remarkable copy
      number variation (CNV), which predisposes for solid tumors and influences drug
      response. Here, we identify a yet undescribed UGT2B17 mRNA overexpression in poor
      risk chronic lymphocytic leukemia (CLL). In total, 320 CLL patients and 449
      healthy donors were analyzed. High (above median) UGT2B17 expression was
      associated with established CLL poor prognostic factors and resulted in shorter
      treatment-free and overall survival (hazard ratio ([death] 2.18; 95% CI 1.18
      4.01; P = .013). The prognostic impact of mRNA expression was more significant
      than that of UGT2B17 CNV. UGT2B17 mRNA levels in primary CLL samples directly
      correlated with functional glucuronidation activity toward androgens and the
      anticancer drug vorinostat (R > 0.9, P < .001). After treatment with fludarabine
      containing regimens UGT2B17 was up-regulated particularly in poor responders (P =
      .030). We observed an exclusive involvement of the 2B17 isoform within the UGT
      protein family. Gene expression profiling of a stable UGT2B17 knockdown in the
      CLL cell line MEC-1 demonstrated a significant involvement in key cellular
      processes. These findings establish a relevant role of UGT2B17 in CLL with
      functional consequences and potential therapeutic implications.

PMID- 23169783
TI  - Structural framework of c-Src activation by integrin beta3.
AB  - The integrin beta3-mediated c-Src priming and activation, via the SH3 domain, is
      consistently associated with diseases, such as the formation of thrombosis and
      the migration of tumor cells. Conventionally, activation of c-Src is often
      induced by the binding of proline-rich sequences to its SH3 domain. Instead,
      integrin beta3 uses R(760)GT(762) for priming and activation. Because of the lack
      of structural information, it is not clear where RGT will bind to SH3, and under
      what mechanism this interaction can prime/activate c-Src. In this study, we
      present a 2.0-A x-ray crystal structure in which SH3 is complexed with the RGT
      peptide. The binding site lies in the "N"-Src loop of the SH3 domain. Structure
      based site-directed mutagenesis showed that perturbation on the "N"-Src loop
      disrupts the interaction between the SH3 domain and the RGT peptide. Furthermore,
      the simulated c-Src:beta3 complex based on the crystal structure of SH3:RGT
      suggests that the binding of the RGT peptide might disrupt the intramolecular
      interaction between the SH3 and linker domains, leading to the disengagement of
      Trp260:"C"-helix and further activation of c-Src.

PMID- 23169785
TI  - Pex11alpha deficiency impairs peroxisome elongation and division and contributes
      to nonalcoholic fatty liver in mice.
AB  - Hepatic triglyceride (TG) accumulation is considered to be a prerequisite for
      developing nonalcoholic fatty liver (NAFL). Peroxisomes have many important
      functions in lipid metabolism, including fatty acid beta-oxidization. However,
      the pathogenic link between NAFL and peroxisome biogenesis remains unclear. To
      examine the molecular and physiological functions of the Pex11alpha gene, we
      disrupted this gene in mice. Body weights and hepatic TG concentrations in
      Pex11alpha(-/-) mice were significantly higher than those in wild-type (WT) mice
      fed a normal or a high-fat diet. Hepatic TG concentrations in fasted Pex11alpha(
      /-) mice were significantly higher than those in fasted WT mice. Plasma TG levels
      increased at lower rates in Pex11alpha(-/-) mice than in WT mice after treatment
      with the lipoprotein lipase inhibitor tyloxapol. The number of peroxisomes was
      lower in the livers of Pex11alpha(-/-) mice than in those of WT mice.
      Ultrastructural analysis showed that small and regular spherically shaped
      peroxisomes were more prevalent in Pex11alpha(-/-) mice fed normal chow
      supplemented without or with fenofibrate. We observed a significantly higher
      ratio of empty peroxisomes containing only PMP70, a peroxisome membrane protein,
      but not catalase, a peroxisome matrix protein, in Pex11alpha(-/-) mice. The mRNA
      expression levels of peroxisomal fatty acid oxidation-related genes (ATP-binding
      cassette, subfamily D, member 2, and acyl-CoA thioesterase 3) were significantly
      higher in WT mice than those in Pex11alpha(-/-) mice under fed conditions. Our
      results demonstrate that Pex11alpha deficiency impairs peroxisome elongation and
      abundance and peroxisomal fatty acid oxidation, which contributes to increased
      lipid accumulation in the liver.

PMID- 23169784
TI  - Brown adipose tissue and its modulation by a mitochondria-targeted peptide in rat
      burn injury-induced hypermetabolism.
AB  - Hypermetabolism is a prominent feature of burn injury, and altered mitochondria
      function is presumed to contribute to this state. Recently, brown adipose tissue
      (BAT) was found to be present not only in rodents but also in humans, and its
      activity is associated with resting metabolic rate. In this report, we elucidate
      the relationship between burn injury-induced hypermetabolism and BAT activity and
      the possible role of the mitochondria-targeted peptide SS31 in attenuating burn
      injury-induced hypermetabolism by using a rat burn injury model. We demonstrate
      that burn injury induces morphological changes in interscapular BAT (iBAT). Burn
      injury was associated with iBAT activation, and this effect was positively
      correlated with increased energy expenditure. BAT activation was associated with
      augmentation of mitochondria biogenesis, and UCP1 expression in the isolated iBAT
      mitochondria. In addition, the mitochondria-targeted peptide SS31 attenuated burn
      injury-induced hypermetabolism, which was accompanied by suppression of UCP1
      expression in isolated mitochondria. Our results suggest that BAT plays an
      important role in burn injury-induced hypermetabolism through its morphological
      changes and expression of UCP1.

PMID- 23169786
TI  - Constitutive expression of pregnancy-associated plasma protein-A in arterial
      smooth muscle reduces the vascular response to injury in vivo.
AB  - Pregnancy-associated plasma protein-A (PAPP-A) functions to increase local IGF-I
      bioactivity. In this study, we used transgenic mice that constitutively express
      human PAPP-A in arterial smooth muscle to test the hypothesis that overexpression
      of PAPP-A enhances vascular smooth muscle cell (SMC) response to IGF-I in vivo.
      PAPP-A transgenic (Tg) and wild-type (WT) mice underwent unilateral carotid
      ligation, a model of injury-induced SMC hyperplasia and neointimal formation. In
      both WT and PAPP-A Tg mice, endogenous PAPP-A mRNA expression showed peak
      elevation 5 days after carotid ligation. However, PAPP-A Tg mice had 70-75% less
      neointima than WT at 5 and 10 days postligation, with a significant reduction in
      occlusion of the ligated artery. WT and PAPP-A Tg mice had equivalent increases
      in medial area and vessel remodeling postligation. There was little change in
      medial area and no evidence of neointima in the contralateral carotid of WT or
      PAPP-A Tg mice. Both WT and PAPP-A Tg carotids exhibited signs of
      dedifferentiation of SMC, which precedes the increase in proliferation and
      migration that results in neointimal formation. However, the number of
      proliferating cells in the media and neointima of the ligated PAPP-A Tg artery
      was reduced by 90% on day 5 postsurgery compared with WT. This decrease was
      associated with a significant decrease in an in vivo marker of IGF-I bioactivity
      and reduced IGF-I-stimulated receptor phosphorylation ex vivo. These data suggest
      differential effects of chronic (transgenic) and transient (endogenous) PAPP-A
      expression on neointimal formation following vascular injury that may be due in
      part to the differential impact on IGF-I signaling.

PMID- 23169787
TI  - Long-term, intermittent, insulin-induced hypoglycemia produces marked obesity
      without hyperphagia or insulin resistance: a model for weight gain with intensive
      insulin therapy.
AB  - A major side effect of insulin treatment of diabetes is weight gain, which limits
      patient compliance and may pose additional health risks. Although the mechanisms
      responsible for this weight gain are poorly understood, it has been suggested
      that there may be a link to the incidence of recurrent episodes of hypoglycemia.
      Here we present a rodent model of marked weight gain associated with weekly
      insulin-induced hypoglycemic episodes in the absence of diabetes. Insulin
      treatment caused a significant increase in both body weight and fat mass,
      accompanied by reduced motor activity, lowered thermogenesis in response to a
      cold challenge, and reduced brown fat uncoupling protein mRNA. However, there was
      no effect of insulin treatment on total food intake nor on hypothalamic
      neuropeptide Y or proopiomelanocortin mRNA expression, and insulin-treated
      animals did not become insulin-resistant. Our results suggest that repeated
      iatrogenic hypoglycemia leads to weight gain, and that such weight gain is
      associated with a multifaceted deficit in metabolic regulation rather than to a
      chronic increase in caloric intake.

PMID- 23169789
TI  - beta-Adrenergic signaling stimulates osteoclastogenesis via reactive oxygen
      species.
AB  - Sympathetic signaling regulates bone resorption through receptor activator of
      nuclear factor-kappaB ligand (RANKL) expression via the beta-adrenergic receptor
      (beta-AR) on osteoblasts. Reactive oxygen species (ROS) are known as one type of
      osteoclast regulatory molecule. Here we show that an antioxidant, alpha-lipoic
      acid (alpha-LA), treatment prevent the beta-adrenergic signaling-induced bone
      loss by suppressing osteoclastogenesis, and sympathetic signaling directly
      regulates osteoclastogenesis through beta2-AR expressed on osteoclasts via
      intracellular ROS generation. In an in vitro study, the beta-AR agonist
      isoprenaline increased intracellular ROS generation in osteoclasts prepared from
      bone marrow macrophages (BBMs) and RAW 264.7 cells. Isoprenaline enhanced
      osteoclastogenesis through beta2-AR expressed on BMMs and RAW 264.7 cells. The
      antioxidant alpha-LA inhibited isoprenaline-enhanced osteoclastogenesis.
      Isoprenaline increased the expression of osteoclast-related genes such as nuclear
      factor of activated T cells, cytoplasmic, calcineurin-dependent 1, tartrate
      resistant acid phosphatase, and cathepsin K on osteoclasts. alpha-LA also
      inhibited isoprenaline-induced increases of these gene expressions. These in
      vitro results led to the hypothesis that beta-adrenergic signaling directly
      stimulates osteoclastogenesis via ROS generation. In an in vivo study,
      isoprenaline treatment alone caused oxidative damage in local bone and reduced
      bone mass because of an increase in bone resorption, and, in alpha-LA-treated
      mice, isoprenaline did not increase tibial osteoclast number even though the
      RANKL-to-osteoprotegerin ratio increased. These in vitro and in vivo results
      indicate that beta-adrenergic signaling, at least in part, directly stimulates
      osteoclastogenesis through beta2-AR on osteoclasts via ROS generation.

PMID- 23169788
TI  - c-Yes regulates cell adhesion at the apical ectoplasmic specialization-blood
      testis barrier axis via its effects on protein recruitment and distribution.
AB  - During spermatogenesis, extensive restructuring takes place at the cell-cell
      interface since developing germ cells migrate progressively from the basal to the
      adluminal compartment of the seminiferous epithelium. Since germ cells per se are
      not motile cells, their movement relies almost exclusively on the Sertoli cell.
      Nonetheless, extensive exchanges in signaling take place between these cells in
      the seminiferous epithelium. c-Yes, a nonreceptor protein tyrosine kinase
      belonging to the Src family kinases (SFKs) and a crucial signaling protein, was
      recently shown to be upregulated at the Sertoli cell-cell interface at the blood
      testis barrier (BTB) at stages VIII-IX of the seminiferous epithelial cycle of
      spermatogenesis. It was also highly expressed at the Sertoli cell-spermatid
      interface known as apical ectoplasmic specialization (apical ES) at stage V to
      early stage VIII of the epithelial cycle during spermiogenesis. Herein, it was
      shown that the knockdown of c-Yes by RNAi in vitro and in vivo affected both
      Sertoli cell adhesion at the BTB and spermatid adhesion at the apical ES, causing
      a disruption of the Sertoli cell tight junction-permeability barrier function,
      germ cell loss from the seminiferous epithelium, and also a loss of spermatid
      polarity. These effects were shown to be mediated by changes in distribution
      and/or localization of adhesion proteins at the BTB (e.g., occludin, N-cadherin)
      and at the apical ES (e.g., nectin-3) and possibly the result of changes in the
      underlying actin filaments at the BTB and the apical ES. These findings implicate
      that c-Yes is a likely target of male contraceptive research.

PMID- 23169790
TI  - Assessing radiologist performance using combined digital mammography and breast
      tomosynthesis compared with digital mammography alone: results of a multicenter,
      multireader trial.
AB  - PURPOSE: To compare radiologists' diagnostic accuracy and recall rates for breast
      tomosynthesis combined with digital mammography versus digital mammography alone.
      MATERIALS AND METHODS: Institutional review board approval was obtained at each
      accruing institution. Participating women gave written informed consent.
      Mediolateral oblique and craniocaudal digital mammographic and tomosynthesis
      images of both breasts were obtained from 1192 subjects. Two enriched reader
      studies were performed to compare digital mammography with tomosynthesis against
      digital mammography alone. Study 1 comprised 312 cases (48 cancer cases) with
      images read by 12 radiologists; study 2, 312 cases (51 cancer cases) with 15
      radiologists. Study 1 readers recorded only that an abnormality requiring recall
      was present; study 2 readers had additional training and recorded both lesion
      type and location. Diagnostic accuracy was compared with receiver operating
      characteristic analysis. Recall rates of noncancer cases, sensitivity,
      specificity, and positive and negative predictive values determined by analyzing
      Breast Imaging Reporting and Data System scores were compared for the two
      methods. RESULTS: Diagnostic accuracy for combined tomosynthesis and digital
      mammography was superior to that of digital mammography alone. Average difference
      in area under the curve in study 1 was 7.2% (95% confidence interval [CI]: 3.7%,
      10.8%; P < .001) and in study 2 was 6.8% (95% CI: 4.1%, 9.5%; P < .001). All 27
      radiologists increased diagnostic accuracy with addition of tomosynthesis. Recall
      rates for noncancer cases for all readers significantly decreased with addition
      of tomosynthesis (range, 6%-67%; P < .001 for 25 readers, P < .03 for all
      readers). Increased sensitivity was largest for invasive cancers: 15% and 22% in
      studies 1 and 2 versus 3% for in situ cancers in both studies. CONCLUSION:
      Addition of tomosynthesis to digital mammography offers the dual benefit of
      significantly increased diagnostic accuracy and significantly reduced recall
      rates for noncancer cases. SUPPLEMENTAL MATERIAL:
      http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.12120674/-/DC1.

PMID- 23169791
TI  - A review of interval breast cancers diagnosed among participants of the Nova
      Scotia Breast Screening Program.
AB  - PURPOSE: To conduct a radiologic review of interval breast cancer cases to
      determine rates of true interval and missed cancers in Nova Scotia, Canada.
      MATERIALS AND METHODS: This quality assurance project was exempt from
      institutional review board approval. Interval cancer cases were identified among
      women aged 40-69 years who were participants in the Nova Scotia Breast Screening
      Program from 1991 to 2004. For each case, the index negative screening mammogram
      was reviewed blindly by three radiologists from a pool of experienced
      radiologists. Cases were identified as those with normal or abnormal findings,
      the latter being a case that required further investigation. True interval cases
      were identified as cases in which a minimum of two radiologists reviewed the
      findings as normal. True interval and missed cancer rates were calculated
      separately for women according to age group and screening interval (for ages 40
      49 years, a 1-year interval; for ages 50-69 years, a 1-year and a 2-year
      interval). RESULTS: The rate of missed cancers per 1000 women screened was one
      half of the true interval rate among women screened annually (for ages 40-49
      years, 0.45 vs 0.93; for ages 50-69 years, 1.08 vs 2.22). Among women aged 50-69
      years who were screened biennially, the rate of missed cancers per 1000 women
      screened was one-third of the true interval rate (0.90 vs 3.15). Similarly, the
      rate of missed cancers per 10,000 screening examinations was one-half of the true
      interval rate among those 40-49 years old (1.95 vs 3.99) and one-third of the
      true interval rate among those 50-69 years old (3.34 vs 10.44). CONCLUSION: In
      screening programs, true interval cancer rates should be differentiated from
      missed cancer rates as part of ongoing quality assurance.

PMID- 23169792
TI  - Non-small cell lung cancer: histopathologic correlates for texture parameters at
      CT.
AB  - PURPOSE: To correlate computed tomographic (CT) texture in non-small cell lung
      cancer (NSCLC) with histopathologic markers for angiogenesis and hypoxia.
      MATERIALS AND METHODS: The study was institutional review board approved, and
      informed consent was obtained. Fourteen patients with NSCLC underwent CT prior to
      intravenous administration of pimonidazole (0.5 g/m(2)), a marker of hypoxia, 24
      hours before surgery. Texture was assessed for unenhanced and contrast material
      enhanced CT images by using a software algorithm that selectively filters and
      extracts texture at different anatomic scales (1.0 [fine detail] to 2.5 [coarse
      features]), with quantification of the standard deviation (SD) of all pixel
      values and the mean value of positive pixels (MPP) and uniformity of distribution
      of positive gray-level pixel values (UPP). After surgery, matched tumor sections
      were stained for angiogenesis (CD34 expression) and for markers of hypoxia
      (glucose transporter protein 1 [Glut-1] and pimonidazole). The percentage and
      average intensity of the tumor stained were assessed. A linear mixed-effects
      model was used to assess the correlations between CT texture and staining
      intensity. RESULTS: SD and MPP quantified from medium to coarse texture on
      contrast-enhanced CT images showed significant associations with the average
      intensity of tumor staining with pimonidazole (for SD: filter value, 2.5; slope =
      0.003; P = .0003). UPP (medium to coarse texture) on unenhanced CT images showed
      a significant inverse association with tumor Glut-1 expression (filter value,
      2.5; slope = -115.13; P = .0008). MPP quantified from medium to coarse texture on
      both unenhanced and contrast-enhanced CT images showed significant inverse
      associations with tumor CD34 expression (unenhanced CT: filter value, 1.8; slope
      = -0.0008; P = .003; contrast-enhanced CT: filter value, 1.8; slope = -0.0006; P
      = .004). CONCLUSION: Texture parameters derived from CT images of NSCLC have the
      potential to act as imaging correlates for tumor hypoxia and angiogenesis.
      SUPPLEMENTAL MATERIAL:
      http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.12112428/-/DC1.

PMID- 23169793
TI  - Filtered back projection, adaptive statistical iterative reconstruction, and a
      model-based iterative reconstruction in abdominal CT: an experimental clinical
      study.
AB  - PURPOSE: To compare objective and subjective image quality parameters of three
      image reconstruction algorithms of different generations at routine multidetector
      computed tomographic (CT) examinations of the abdomen. MATERIALS AND METHODS:
      This institutional review board-approved study included 22 consecutive patients
      (mean age, 56.1 years +/- 15.8 [standard deviation]; mean weight, 79.1 kg +/-
      14.8) who underwent routine CT examinations of the abdomen. A low-contrast
      phantom was used for objective quality control. Raw data sets were reconstructed
      by using filtered back projection (FPB), adaptive statistical iterative
      reconstruction (ASIR), and a model-based iterative reconstruction (MBIR).
      Radiologists used a semiquantitative scale (-3 to +3) to rate subjective image
      quality and artifacts, comparing both FBP and MBIR images with ASIR images. The
      Wilcoxon test and the intraclass correlation coefficient were used to evaluate
      the data. Measurements of objective noise and CT numbers of soft tissue
      structures were compared with analysis of variance. RESULTS: The phantom study
      revealed an improved detectability of low-contrast targets for MBIR compared with
      ASIR or FBP. Subjective ratings showed higher image quality for MBIR, with better
      resolution (median value, 2; range, 1 to 3), lower noise (2; range, 1 to 3), and
      finer contours (2; range, 1 to 2) compared with ASIR (all P < .001). FBP
      performed inferiorly (0, range, -2 to 0]; -1 [range, -3 to 0]; 0 [range, -1 to
      0], respectively; all, P < .001). Mean interobserver correlation was 0.9 for
      image perception and 0.7 for artifacts. Objective noise for FBP was 14%-68%
      higher and for MBIR was 18%-47% lower than that for ASIR (P < .001). CONCLUSION:
      The MBIR algorithm considerably improved objective and subjective image quality
      parameters of routine abdominal multidetector CT images compared with those of
      ASIR and FBP.

PMID- 23169795
TI  - Irreversible electroporation ablation: is all the damage nonthermal?
AB  - PURPOSE: To determine whether high-dose irreversible electroporation (IRE)
      ablation induces thermal effects in normal liver tissue. MATERIALS AND METHODS:
      Animal care and use committee approval was obtained prior to the experiments. IRE
      ablation (n = 78) was performed by a single four-person team in vivo in 22
      porcine livers by applying electric current to two 1.3-cm-diameter circular flat
      plate electrodes spaced 1 cm apart. Cardiac-gated IRE pulses (n = 40-360) were
      systematically applied at varying voltages (1500-2900 V). End temperatures at the
      ablation zone center were measured and were correlated with ablation time, energy
      parameters, and resultant treatment effect as determined at gross pathologic and
      histopathologic examination. Temperatures were then monitored at the center and
      periphery of four ablations created by using a four-electrode IRE array (3000 V,
      90 pulses per electrode pair). Data were analyzed by using multivariate analysis
      of variance with multiple comparisons and/or paired t tests and regression
      analysis, as appropriate. RESULTS: Temperature rose above the 34 degrees C
      baseline after IRE in all flat-plate experiments and correlated linearly (R(2) =
      0.39) with IRE "energy dose" (product of voltage and number of pulses) and more
      tightly in univariate analysis with both voltage and number of pulses. Thus, mean
      temperatures as high as 86 degrees C +/- 3 (standard deviation) were seen for
      2500 V and 270 pulses. Ablations of 90 pulses or more at 2500 V produced
      temperatures of 50 degrees C or greater and classic gross and histopathologic
      findings of thermal coagulation (pyknotic nuclei and streaming cytoplasm). For
      lower IRE doses (ie, 2100 V, 90 pulses), temperatures remained below 45 degrees
      C, and only IRE-associated pathologic findings (ie, swollen sinusoids, dehydrated
      cells, and hemorrhagic infiltrate) were seen. For the four-electrode arrays,
      temperatures measured 54.2 degrees C +/- 6.1 at the electrode surfaces and 38.6
      degrees C +/- 3.2 at the ablation zone margin. CONCLUSION: In some conditions of
      high intensity, IRE can produce sufficient heating to induce "white zone" thermal
      coagulation. While this can be useful in some settings to increase tumor
      destruction, further characterization of the thermal profile created with
      clinical electrodes and energy parameters is therefore needed to better
      understand the best ways to avoid unintended damage when ablating near thermally
      sensitive critical structures.

PMID- 23169794
TI  - Evaluation of clinically translatable MR imaging biomarkers of therapeutic
      response in the TH-MYCN transgenic mouse model of neuroblastoma.
AB  - PURPOSE: To evaluate noninvasive and clinically translatable magnetic resonance
      (MR) imaging biomarkers of therapeutic response in the TH-MYCN transgenic mouse
      model of aggressive, MYCN-amplified neuroblastoma. MATERIALS AND METHODS: All
      experiments were performed in accordance with the local ethical review panel and
      the UK Home Office Animals Scientific Procedures Act 1986 and with the UK
      National Cancer Research Institute guidelines for the welfare of animals in
      cancer research. Multiparametric MR imaging was performed of abdominal tumors
      found in the TH-MYCN model. T2-weighted MR imaging, quantitation of native
      relaxation times T1 and T2, the relaxation rate R2*, and dynamic contrast
      enhanced MR imaging were used to monitor tumor response to cyclophosphamide (25
      mg/kg), the vascular disrupting agent ZD6126 (200 mg/kg), or the antiangiogenic
      agent cediranib (6 mg/kg, daily). Any significant changes in the measured
      parameters, and in the magnitude of the changes after treatment between treated
      and control cohorts, were identified by using Student two-tailed paired and
      unpaired t test, respectively, with a 5% level of significance. RESULTS:
      Treatment with cyclophosphamide or cediranib induced a 54% or 20% reduction in
      tumor volume at 48 hours, respectively (P < .005 and P < .005, respectively; P <
      .005 and P < .005 versus control, respectively). Treatment with ZD6126 induced a
      45% reduction in mean tumor volume 24 hours after treatment (P < .005; P < .005
      versus control). The antitumor activity of cyclophosphamide, cediranib, and
      ZD6126 was consistently associated with a decrease in tumor T1 (P < .005, P <
      .005, and P < .005, respectively; P < .005, P < .005, and P < .005 versus
      control, respectively) and with a correlation between therapy-induced changes in
      native T1 and changes in tumor volume (r = 0.56; P < .005). Tumor response to
      cediranib was also associated with a decrease in the dynamic contrast-enhanced MR
      imaging-derived volume transfer constant (P = .07; P < .05 versus control) and
      enhancing fraction (P < .05; P < .01 versus control), and an increase in R2* (P <
      .005; P < .05 versus control). CONCLUSION: The T1 relaxation time is a robust
      noninvasive imaging biomarker of response to therapy in tumors in TH-MYCN mice,
      which emulate high-risk neuroblastoma in children. T1 measurements can be readily
      implemented on clinical MR systems and should be investigated in translational
      clinical trials of new targeted therapies for pediatric neuroblastoma.
      SUPPLEMENTAL MATERIAL:
      http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.12120128/-/DC1.

PMID- 23169796
TI  - Hepatic fibrosis: evaluation with semiquantitative contrast-enhanced CT.
AB  - PURPOSE: To evaluate the feasibility of using contrast material-enhanced computed
      tomographic (CT) measurements of hepatic fractional extracellular space (fECS)
      and macromolecular contrast material (MMCM) uptake to measure severity of liver
      fibrosis. MATERIALS AND METHODS: All procedures were approved by and executed in
      accordance with University of California, San Francisco, institutional animal
      care and use committee regulations. Twenty-one rats that received intragastric
      CCl(4) for 0-12 weeks were imaged with respiratory-gated micro-CT by using both a
      conventional contrast material and a novel iodinated MMCM. Histopathologic
      hepatic fibrosis was graded qualitatively by using the Ishak fibrosis score and
      quantitatively by using morphometry of the fibrosis area. Hepatic fECS and MMCM
      uptake were calculated for each examination and correlated with histopathologic
      findings by using uni- and multivariate linear regressions. RESULTS: Ishak
      fibrosis scores ranged from a baseline of 0 in untreated animals to a maximum of
      5. Histopathologic liver fibrosis area increased from 0.46% to 3.5% over the same
      interval. Strong correlations were seen between conventional contrast-enhanced CT
      measurements of fECS and both the Ishak fibrosis scores (R(2) = 0.751, P < .001)
      and the fibrosis area (R(2) = 0.801, P < .001). Strong negative correlations were
      observed between uptake of MMCM in the liver and Ishak fibrosis scores (R(2) =
      0.827, P < .001), as well as between uptake of MMCM in the liver and fibrosis
      area (R(2) = 0.643, P = .001). Multivariate linear regression analysis showed a
      trend toward independence for fECS and MMCM uptake in the prediction of Ishak
      fibrosis scores, with an R(2) value of 0.86 (P = .081 and P = .033,
      respectively). CONCLUSION: Contrast-enhanced CT measurements of fECS and MMCM
      uptake are individually capable of being used to estimate the degree of early
      hepatic fibrosis in a rat model. SUPPLEMENTAL MATERIAL:
      http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.12112452/-/DC1.

PMID- 23169797
TI  - Kidney transplant: functional assessment with diffusion-tensor MR imaging at 3T.
AB  - PURPOSE: To evaluate the feasibility of diffusion-tensor (DT) imaging at 3 T for
      functional assessment of transplanted kidneys. MATERIALS AND METHODS: This study
      was approved by the local ethics committee; written informed consent was
      obtained. Between August 2009 and October 2010, 40 renal transplant recipients
      were prospectively included in this study and examined with a clinical 3-T
      magnetic resonance (MR) imager. An echo-planar DT imaging sequence was performed
      in coronal orientation by using five b values (0, 200, 400, 600, 800 sec/mm(2))
      and 20 diffusion directions. The fractional anisotropy (FA) and apparent
      diffusion coefficient (ADC) were determined for the cortex and medulla of the
      transplanted kidney. Relationships between FA, ADC, and allograft function,
      determined by the estimated glomerular filtration rate (eGFR), were assessed by
      using Pearson correlation coefficient. ADC and FA were compared between patients
      with good or moderate allograft function (group A; eGFR > 30 mL/min/1.73 m(2))
      and patients with impaired function (group B; eGFR <= 30 mL/min/1.73 m(2)) by
      using a student t test. P < .05 indicated a statistically significant difference.
      RESULTS: Mean FA of the renal medulla and cortex was significantly higher in
      group A (0.39 +/- 0.06 and 0.17 +/- 0.4) compared with group B (0.27 +/- 0.05 and
      0.14 +/- 0.03) (P < .001 and P = .009, respectively). Mean ADCs of renal cortex
      and medulla were significantly higher in group A than in group B (P = .007 and P
      = .01, respectively). In group B, mean medullary FA was significantly lower in
      patients whose renal function did not recover (0.22 +/- 0.02) compared with those
      with stable allograft function at 6 months (0.29 +/- 0.05, P < .001). There was
      significant correlation between eGFR and medullary FA (r = 0.65, P < .001),
      cortical ADC (r = 0.43, P = .003), and medullary ADC (r = 0.35, P = .01).
      CONCLUSION: DT imaging is a promising noninvasive technique for functional
      assessment of renal allografts. FA values in the renal medulla exhibit a good
      correlation with renal function.

PMID- 23169798
TI  - Exercise-induced bronchoconstriction: reproducibility of hyperpolarized 3He MR
      imaging.
AB  - PURPOSE: To quantitatively evaluate interday, interreader, and intersite
      agreement of readers of hyperpolarized helium 3 (HPHe) MR images in patients with
      exercise-induced bronchoconstriction. MATERIALS AND METHODS: This HIPAA
      compliant, institutional review board approved study included 13 patients with
      exercise-induced bronchoconstriction. On two separate days, HPHe MR imaging of
      the lungs was performed at baseline, immediately after a 10-minute exercise
      challenge (postchallenge), and 45 minutes after exercise (recovery). Patients
      were imaged at two sites, six at site A and seven at site B. Images were analyzed
      independently by multiple readers at each site. Lung volume, ventilation defect
      volume, ventilated volume, and the number of defects were measured
      quantitatively, and the location of defects was evaluated qualitatively at site
      A. Interday and interreader agreement were evaluated by using the intraclass
      correlation coefficient (ICC), and intersite agreement was evaluated by using a
      modified Bland-Altman analysis. RESULTS: The ICC between days for ventilation
      defect volume, ventilated volume, and number of defects was at least 0.74 at both
      sites. The ICC for lung volume was greater at site B (0.83-0.86) than at site A
      (0.60-0.65). Defects seen in the same location in the lung on both days included
      19.7% of those seen on baseline images and 29.2% and 18.6% of defects on
      postchallenge and recovery images, respectively. Interreader ICC for each
      measurement was at least 0.82 for each site. Analysis of intersite agreement
      showed biases of 612 mL for lung volume, -60.7 mL for ventilation defect volume,
      2.91% for ventilated volume, and -6.56 for number of defects. CONCLUSION: The
      reported measures of reproducibility of HPHe MR imaging may help in the design
      and interpretation of single- and multicenter studies of patients with exercise
      induced bronchoconstriction.

PMID- 23169799
TI  - Identification of small RNAs in Mycobacterium smegmatis using heterologous Hfq.
AB  - Gene regulation by small RNAs (sRNAs) has been extensively studied in various
      bacteria. However, the presence and roles of sRNAs in mycobacteria remain largely
      unclear. Immunoprecipitation of RNA chaperone Hfq to enrich for sRNAs is one of
      the effective methods to isolate sRNAs. However, the lack of an identified
      mycobacterial hfq restricts the feasibility of this approach. We developed a
      novel method that takes advantage of the conserved inherent sRNAs-binding
      capability of heterologous Hfq from Escherichia coli to enrich sRNAs from
      Mycobacterium smegmatis, a model organism for studying Mycobacterium
      tuberculosis. We validated 12 trans-encoded and 12 cis-encoded novel sRNAs in M.
      smegmatis. Many of these sRNAs are differentially expressed at exponential phase
      compared with stationary phase, suggesting that sRNAs are involved in the growth
      of mycobacteria. Intriguingly, five of the cis-encoded novel sRNAs target known
      transposases. Phylogenetic conservation analysis shows that these sRNAs are
      pathogenicity dependent. We believe that our findings will serve as an important
      reference for future analysis of sRNAs regulation in mycobacteria and will
      contribute significantly to the development of sRNAs prediction programs.
      Moreover, this novel method of using heterologous Hfq for sRNAs enrichment can be
      of general use for the discovery of bacterial sRNAs in which no endogenous Hfq is
      identified.

PMID- 23169800
TI  - Systematic evaluation of medium-throughput mRNA abundance platforms.
AB  - Profiling of mRNA abundances with high-throughput platforms such as microarrays
      and RNA-seq has become an important tool in both basic and biomedical research.
      However, these platforms remain prone to systematic errors and have challenges in
      clinical and industrial applications. As a result, it is standard practice to
      validate a subset of key results using alternate technologies. Similarly,
      clinical and industrial applications typically involve transitions from a high
      throughput discovery platform to medium-throughput validation ones. These medium
      throughput validation platforms have high technical reproducibility and reduced
      sample input needs, and low sensitivity to sample quality (e.g., for processing
      FFPE specimens). Unfortunately, while medium-throughput platforms have
      proliferated, there are no comprehensive comparisons of them. Here we fill that
      gap by comparing two key medium-throughput platforms--NanoString's nCounter
      Analysis System and ABI's OpenArray System--to gold-standard quantitative real
      time RT-PCR. We quantified 38 genes and positive and negative controls in 165
      samples. Signal:noise ratios, correlations, dynamic range, and detection accuracy
      were compared across platforms. All three measurement technologies showed good
      concordance, but with divergent price/time/sensitivity trade-offs. This study
      provides the first detailed comparison of medium-throughput RNA quantification
      platforms and provides a template and a standard data set for the evaluation of
      additional technologies.

PMID- 23169802
TI  - Resistant hypertension.

PMID- 23169803
TI  - Restless legs syndrome.

PMID- 23169804
TI  - The use of highly structured care to achieve blood pressure targets.

PMID- 23169805
TI  - A short history of pharmaceutical marketing.

PMID- 23169806
TI  - Reviewers question the use of antibiotics for uncomplicated diverticulitis.

PMID- 23169807
TI  - Ten valent vaccine prevents most invasive pneumococcal disease.

PMID- 23169808
TI  - Probiotics prevent Clostridium difficile in people taking antibiotics.

PMID- 23169809
TI  - Faking it.

PMID- 23169810
TI  - GP is held entirely responsible for brain damage of child who was discharged from
      hospital after head injury.

PMID- 23169811
TI  - Practical application of suspension criteria scenarios in general radiography,
      computed radiography,digital radiography and fluoroscopy.
AB  - Radiological equipment must be assessed against criteria for acceptability to
      ensure that it meets the minimum standards for patient safety. This assessment is
      typically led by a medical physicist with input from radiology staff and the
      equipment supplier. Equipment that does not meet the criteria requires action and
      may be suspended from clinical use. European Commission report RP 91 will be
      revised and replaced as RP 162. It has been drawn up to aid medical physicists
      with the assessment process and provide guidance on suspension levels. This paper
      details several cases where the criteria in the proposed RP 162 were applied in
      general radiography, computed radiography, digital radiography and fluoroscopy.
      The factors considered by the medical physicist and the outcome of each case are
      presented. The proposed RP 162 report improves on its predecessor and provides a
      robust set of criteria for ensuring that patient safety within the EU medical
      exposures framework is optimised.

PMID- 23169801
TI  - Effect of intensive structured care on individual blood pressure targets in
      primary care: multicentre randomised controlled trial.
AB  - OBJECTIVE: To determine the effectiveness of intensive structured care to
      optimise blood pressure control based on individual absolute risk targets in
      primary care. DESIGN: Pragmatic multicentre randomised controlled trial. SETTING:
      General practices throughout Australia, except Northern Territory, 2009-11.
      PARTICIPANTS: Of 2185 patients from 119 general practices who were eligible for
      drug treatment for hypertension according to national guidelines 416 (19.0%)
      achieved their individual blood pressure target during a 28 day run-in period of
      monotherapy. After exclusions, 1562 participants not at target blood pressure
      (systolic 150 (SD 17) mm Hg, diastolic 88 (SD 11) mm Hg) were randomised (1:2
      ratio) to usual care (n=524) or the intervention (n=1038). INTERVENTION: Computer
      assisted clinical profiling and risk target setting (all participants) with
      intensified follow-up and stepwise drug titration (initial angiotensin receptor
      blocker monotherapy or two forms of combination therapy using angiotensin
      receptor blockers) for those randomised to the intervention. The control group
      received usual care. MAIN OUTCOME MEASURES: The primary outcome was individual
      blood pressure target achieved at 26 weeks. Secondary outcomes were change in
      mean sitting systolic and diastolic blood pressure, absolute risk for
      cardiovascular disease within five years based on the Framingham risk score, and
      proportion and rate of adverse events. RESULTS: On an intention to treat basis,
      there was an 8.8% absolute difference in individual blood pressure target
      achieved at 26 weeks in favour of the intervention group compared with usual care
      group (358/988 (36.2%) v 138/504 (27.4%)): adjusted relative risk 1.28 (95%
      confidence interval 1.10 to 1.49, P=0.0013). There was also a 9.5% absolute
      difference in favour of the intervention group for achieving the classic blood
      pressure target of <= 140/90 mm Hg (627/988 (63.5%) v 272/504 (54.0%)): adjusted
      relative risk 1.18 (1.07 to 1.29, P<0.001). The intervention group achieved a
      mean adjusted reduction in systolic blood pressure of 13.2 mm Hg (95% confidence
      interval -12.3 to -14.2 mm Hg) and diastolic blood pressure of 7.7 mm Hg (-7.1 to
      -8.3 mm Hg) v 10.1 mm Hg (-8.8 to 11.3 mm Hg) and 5.5 mm Hg (-4.7 to -6.2 mm Hg)
      in the usual care group (P<0.001). Among 1141 participants in whom five year
      absolute cardiovascular risk scores were calculated from baseline to the 26 week
      follow-up, the reduction in risk scores was greater in the intervention group
      than usual care group (14.7% (SD 9.3%) to 10.9% (SD 8.0%); difference -3.7% (SD
      4.5%) and 15.0% (SD 10.1%) to 12.4% (SD 9.4%); -2.6% (SD 4.5%): adjusted mean
      difference -1.13% (95% confidence interval -0.69% to -1.63%; P<0.001). Owing to
      adverse events 82 (7.9%) participants in the intervention group and 10 (1.9%) in
      the usual care group had their drug treatment modified. CONCLUSIONS: In a primary
      care setting intensive structured care resulted in higher levels of blood
      pressure control, with clinically lower blood pressure and absolute risk of
      future cardiovascular events overall and with more people achieving their target
      blood pressure. An important gap in treatment remains though and applying
      intensive management and achieving currently advocated risk based blood pressure
      targets is challenging.

PMID- 23169812
TI  - Practical application of suspension criteria scenarios: radiotherapy.
AB  - In 2007, the European Commission (EC) commissioned a group of experts to
      undertake the revision of Report RP91 'Criteria for Acceptability of Radiological
      (including Radiotherapy) and Nuclear Medicine Installations' written in 1997. The
      revised draft report was submitted to the EC in 2010, which issued it for public
      consultation. The EC commissioned the same group of experts to consider the
      comments of the public consultation for further improvement of the revised
      report. The EC intends to publish the final report under its Radiation Report
      Series as RP162. This paper presents a selection of practical applications of
      suspension criteria scenarios in radiotherapy, mostly in brachytherapy, with
      special emphasis on the critical roles and responsibilities of qualified
      radiotherapy staff (radiation oncologists, medical physicists and radiotherapy
      technicians).

PMID- 23169813
TI  - The revision of RP 91 on criteria for acceptability of radiological (including
      radiotherapy) and nuclear medicine installations.
AB  - In 1997 the European Commission published Radiation Protection 91: 'Criteria for
      acceptability of radiological (including radiotherapy) and nuclear medicine
      installations'. This document specified the minimum criteria for acceptability.
      It has been used to this effect in legislation, codes of practice and by
      individual professionals. In a single document, it defined a level of performance
      at which remedial action was required. The document specified a series of
      parameters which characterised equipment performance and acceptable levels of
      performance. In its time it proved to be a useful document which was applied in
      member states to various degrees. Since the publication of Report 91 in 1997, a
      series of weaknesses emerged over time. Development of new radiological systems
      and technologies, as well as improvements in traditional technologies, has
      created circumstances where the acceptability criteria were in need of review.
      These weaknesses were recognised by the European Commission and a tender for its
      revision was issued. The criteria were developed by a team drawn from a broad
      range of backgrounds including hospitals, industry, government bodies, regulators
      and standardisation organisations. Representatives were mainly from Europe, but
      individuals from the American Association of Physicists in Medicine and
      International Atomic Energy Agency were included in the drafting process. This
      study describes the process employed in developing the revised document and the
      consultation process involved. One of the major difficulties the revision team
      encountered was related to an understanding of the actual meaning of the EC
      Directive. The view taken by the revision team was that Article 8, paragraph 3
      places responsibilities on both the holders of radiological equipment and
      competent authorities. The acceptability criteria have been produced consistent
      with the European Commission's Medical Exposures Directive, which requires that
      patient exposures are optimised and justified.

PMID- 23169814
TI  - Development of acceptability criteria in mammography.
AB  - Quality assurance protocols and standards of performance for X-ray mammography
      equipment are probably the most developed of any in the area of diagnostic
      radiology, due to the exacting demands on image quality required in population
      based breast cancer screening programmes. Both qualitative and quantitative
      acceptability criteria have been published for X-ray mammography by considering
      the image quality needed clinically in screening programmes. Consequently, the
      task of developing a consensus for acceptability criteria appears to be
      relatively easy at first glance. However, there are two contentious issues that
      must be considered; the first is whether standards based on breast cancer
      screening can be transposed to equipment used for women referred for imaging with
      breast symptoms. The second relates to the use of image-quality assessment based
      upon the observation of details in test phantoms. In respect of the former, there
      was general agreement that only one set of acceptability criteria should apply to
      mammographic X-ray equipment. With regard to image-quality assessment, the
      weakness of the observer-based methods was recognised and a consensus position
      developed. This paper describes the development of a consensus on acceptability
      criteria and proposes both qualitative and quantitative criteria for use on all
      mammographic equipment. Some test approaches and criteria for image displays, in
      particular, were omitted from the document as concerns about their robustness
      emerged during the consultation phases of the revision. Clearly, further
      scientific work is needed in these areas.

PMID- 23169815
TI  - Suspension criteria for dual energy X ray absorptiometry.
AB  - The use of dual-energy X-ray absorptiometry (DXA) units primarily for the
      assessment of fracture risk and in the diagnosis of osteoporosis is ubiquitous in
      Europe and ever-expanding in its implementation worldwide. DXA is known for its
      reported low radiation dose and precision in the determination of bone mineral
      density. However, the use of simple suspension criteria, as proposed in the new
      EC report RP-162, will identify units that are unfit for useful and safe
      diagnosis. Such suspension levels, however, are not a substitute for regular
      maintenance, quality control testing and optimisation of clinical outcomes.

PMID- 23169816
TI  - Sequential conformational rearrangements dictate the dynamics of class C GPCR
      activation.
AB  - Heterotrimeric GTP-binding protein (G protein)-coupled receptors (GPCRs) are the
      largest family of cell surface receptors; they allow cells to respond to a wide
      range of endogenous and environmental signals. Class C GPCRs represent a discrete
      group within the GPCR family, with distinct structural characteristics. Receptors
      belonging to this class--such as gamma-aminobutyric acid type B (GABA(B))
      receptors or metabotropic glutamate receptors (mGluRs)--form constitutive dimers.
      However, the conformational changes within such a dimeric receptor that are
      associated with agonist activation are still not well understood. A study by
      Hlavackova et al. investigates the role of dimer formation in mGluR1 activation.
      Using fluorescence resonance energy transfer approaches to assess inter- and
      intrasubunit conformational changes, the authors present an elegant study that
      sheds light on the kinetics of domain rearrangements in a class C GPCR upon
      ligand binding.

PMID- 23169817
TI  - Attractor landscape analysis reveals feedback loops in the p53 network that
      control the cellular response to DNA damage.
AB  - The protein p53 functions as a tumor suppressor and can trigger either cell cycle
      arrest or apoptosis in response to DNA damage. We used Boolean network modeling
      and attractor landscape analysis to analyze the state transition dynamics of a
      simplified p53 network for which particular combinations of activation states of
      the molecules corresponded to specific cellular outcomes. Our results identified
      five critical interactions in the network that determined the cellular response
      to DNA damage, and simulations lacking any of these interactions produced states
      associated with sustained p53 activity, which corresponded to a cell death
      response. Attractor landscape analysis of the cellular response to DNA damage of
      the breast cancer cell line MCF7 and the effect of the Mdm2 (murine double minute
      2) inhibitor nutlin-3 indicated that nutlin-3 would exhibit limited efficacy in
      triggering cell death, because the cell death state was not induced to a large
      extent by simulations with nutlin-3 and instead produced a state consistent with
      oscillatory p53 dynamics and cell cycle arrest. Attractor landscape analysis also
      suggested that combining nutlin-3 with inhibition of Wip1 would synergize to
      stimulate a sustained increase in p53 activity and promote p53-mediated cell
      death. We validated this synergistic effect in stimulating p53 activity and
      triggering cell death with single-cell imaging of a fluorescent p53 reporter in
      MCF7 cells. Thus, attractor landscape analysis of p53 network dynamics and its
      regulation can identify potential therapeutic strategies for treating cancer.

PMID- 23169819
TI  - GPRC5B activates obesity-associated inflammatory signaling in adipocytes.
AB  - A genome-wide association study identified a strong correlation between body mass
      index and the presence of a 21-kb copy number variation upstream of the human
      GPRC5B gene; however, the functional role of GPRC5B in obesity remains unknown.
      We report that GPRC5B-deficient mice were protected from diet-induced obesity and
      insulin resistance because of reduced inflammation in their white adipose tissue.
      GPRC5B is a lipid raft-associated transmembrane protein that contains multiple
      phosphorylated residues in its carboxyl terminus. Phosphorylation of GPRC5B by
      the tyrosine kinase Fyn and the subsequent direct interaction with Fyn through
      the Fyn Src homology 2 (SH2) domain were critical for the initiation and
      progression of inflammatory signaling in adipose tissue. We demonstrated that a
      GPRC5B mutant lacking the direct binding site for Fyn failed to activate a
      positive feedback loop of nuclear factor kappaB-inhibitor of kappaB kinase
      epsilon signaling. These findings suggest that GPRC5B may be a major node in
      adipose signaling systems linking diet-induced obesity to type 2 diabetes and may
      open new avenues for therapeutic approaches to diabetic progression.

PMID- 23169818
TI  - SUMOylation silences heterodimeric TASK potassium channels containing K2P1
      subunits in cerebellar granule neurons.
AB  - The standing outward K(+) current (IKso) governs the response of cerebellar
      granule neurons to natural and medicinal stimuli including volatile anesthetics.
      We showed that SUMOylation silenced half of IKso at the surface of cerebellar
      granule neurons because the underlying channels were heterodimeric assemblies of
      K2P1, a subunit subject to SUMOylation, and the TASK (two-P domain, acid
      sensitive K(+)) channel subunits K2P3 or K2P9. The heterodimeric channels
      comprised the acid-sensitive portion of IKso and mediated its response to
      halothane. We anticipate that SUMOylation also influences sensation and
      homeostatic mechanisms in mammals through TASK channels formed with K2P1.

PMID- 23169820
TI  - Cosmetic surgery training in Canadian plastic surgery residencies: are we
      training competent surgeons?
AB  - BACKGROUND: With the demand for cosmetic surgery continuing to rise, it is
      necessary to reevaluate the current state of cosmetic surgery training during
      plastic surgery residency. An evaluation of cosmetic surgery training in US
      plastic surgery residency programs in 2006 identified several areas for
      improvement, resulting in changes to both the duration and content of training.
      OBJECTIVES: The authors assess the current state of cosmetic surgery training in
      Canadian plastic surgery residency programs. METHODS: A paper survey of all
      graduating Canadian plastic surgery residents eligible to complete the 2009 Royal
      College of Physicians and Surgeons of Canada fellowship examinations was
      performed (N = 29). The survey was conducted primarily at the Canadian Plastic
      Surgery Review Course in February 2009, with surveys collected from absent
      residents by e-mail within 1 month after the course. The survey covered 2 broad
      areas: (1) specifics regarding resident cosmetic surgery training and (2)
      confidence and satisfaction associated with this experience. RESULTS: Of the 29
      residents surveyed, 28 responded (96%). The majority of Canadian plastic surgery
      residency programs (75%) have a designated cosmetic surgery rotation, but 90% of
      respondents felt it has become increasingly difficult to gain exposure to
      cosmetic procedures as most are performed at private surgery centers. Elective
      rotations at cosmetic surgery practices and resident cosmetic clinics were
      considered the most beneficial for cosmetic surgery education. Residents
      considered cosmetic surgery procedures of the face (such as rhinoplasty and
      facelift) more challenging, but they had more confidence with breast and body
      contouring procedures. CONCLUSIONS: Canadian plastic surgery residency programs
      need to ensure that residents continue to receive comprehensive exposure to both
      surgical and nonsurgical cosmetic procedures to ensure our specialty's continued
      leadership in this evolving and highly competitive field. A multidimensional
      approach utilizing a variety of readily available resources will ensure that the
      current and future cosmetic surgery educational needs of Canadian plastic surgery
      residents are met.

PMID- 23169822
TI  - Delhi's government asks private hospitals why they aren't providing free care to
      the poor.

PMID- 23169821
TI  - Hair restoration surgery: the state of the art.
AB  - Hair restoration is a highly sophisticated subspecialty that offers significant
      relief to patients with hair loss. An improved understanding of the aesthetics of
      hair loss and cosmetic hair restoration, hair anatomy and physiology, and the
      development of microvascular surgical instrumentation has revolutionized the
      approach to surgical hair restoration since the original description. Additional
      elements that contribute to the current state of the art in hair restoration
      include graft size, site creation, packing density, and medical control of hair
      loss. The results of hair restoration are natural in appearance and are provided
      with a very high level of patient satisfaction and safety. This aspect of
      cosmetic surgery is a very welcome addition to a traditional aesthetic practice
      and serves as a tremendous source for internal cross-referral. The future of hair
      restoration surgery is centered on minimal-incision surgery as well as cell-based
      therapies.

PMID- 23169823
TI  - Obama extends deadline on health exchanges.

PMID- 23169824
TI  - GPs warn of dangers in allowing patients online access to their medical records.

PMID- 23169825
TI  - Health workers in British Columbia must be vaccinated against flu or wear a mask,
      new policy says.

PMID- 23169826
TI  - Death rate from ovarian cancer in England has fallen by a fifth since 2001.

PMID- 23169827
TI  - Almost 50 new psychoactive substances were reported to EU in 2011.

PMID- 23169828
TI  - First meningitis B vaccine could be available in UK next year.

PMID- 23169830
TI  - WHO hits out over reports on links with food industry.

PMID- 23169829
TI  - Greece has highest use of antibiotics outside hospital in Europe.

PMID- 23169831
TI  - Organisations voice concerns over plans to disband Human Tissue Authority.

PMID- 23169833
TI  - Missing notes mean case is postponed against doctor arrested during transit in
      United Arab Emirates.

PMID- 23169832
TI  - Doctors must put needs of child before relationship with parents, judge rules.

PMID- 23169859
TI  - MRI and ultrasonographic findings in idiopathic intracranial hypertension.

PMID- 23169862
TI  - Pillars article: lymphoproliferation disorder in mice explained by defects in Fas
      antigen that mediates apoptosis. 1992.

PMID- 23169863
TI  - Pathogenic long-lived plasma cells and their survival niches in autoimmunity,
      malignancy, and allergy.
AB  - Long-lived plasma cells survive in a protected microenvironment for years or even
      a lifetime and provide humoral memory by establishing persistent Ab titers. Long
      lived autoreactive, malignant, and allergen-specific plasma cells are likewise
      protected in their survival niche and are refractory to immunosuppression, B cell
      depletion, and irradiation. Their elimination remains an essential therapeutic
      challenge. Recent data indicate that long-lived plasma cells reside in a
      multicomponent plasma cell niche with a stable mesenchymal and a dynamic
      hematopoietic component, both providing essential soluble and membrane-bound
      survival factors. Alternative niches with different hematopoietic cell components
      compensate fluctuations of single cell types but may also harbor distinct plasma
      cell subsets. In this Brief Review, we discuss conventional therapies in
      autoimmunity and multiple myeloma in comparison with novel drugs that target
      plasma cells and their niches. In the future, such strategies may enable the
      specific depletion of pathogenic plasma cells while leaving the protective
      humoral memory intact.

PMID- 23169861
TI  - Autoimmunity: twenty years in the Fas lane.

PMID- 23169864
TI  - Outcome quality of in-patient cardiac rehabilitation in elderly patients-
      identification of relevant parameters.
AB  - BACKGROUND: Outcome quality management requires the consecutive registration of
      defined variables. The aim was to identify relevant parameters in order to
      objectively assess the in-patient rehabilitation outcome. METHODS: From February
      2009 to June 2010 1253 patients (70.9 +/- 7.0 years, 78.1% men) at 12
      rehabilitation clinics were enrolled. Items concerning sociodemographic data, the
      impairment group (surgery, conservative/interventional treatment), cardiovascular
      risk factors, structural and functional parameters and subjective health were
      tested in respect of their measurability, sensitivity to change and their
      propensity to be influenced by rehabilitation. RESULTS: The majority of patients
      (61.1%) were referred for rehabilitation after cardiac surgery, 38.9% after
      conservative or interventional treatment for an acute coronary syndrome.
      Functionally relevant comorbidities were seen in 49.2% (diabetes mellitus,
      stroke, peripheral artery disease, chronic obstructive lung disease). In three
      key areas 13 parameters were identified as being sensitive to change and subject
      to modification by rehabilitation: cardiovascular risk factors (blood pressure,
      low-density lipoprotein cholesterol, triglycerides), exercise capacity (resting
      heart rate, maximal exercise capacity, maximal walking distance, heart failure,
      angina pectoris) and subjective health (IRES-24 (indicators of rehabilitation
      status): pain, somatic health, psychological well-being and depression as well as
      anxiety on the Hospital Anxiety and Depression Scale). CONCLUSION: The outcome of
      in-patient rehabilitation in elderly patients can be comprehensively assessed by
      the identification of appropriate key areas, that is, cardiovascular risk
      factors, exercise capacity and subjective health. This may well serve as a
      benchmark for internal and external quality management.

PMID- 23169865
TI  - The region makes the difference: disparities in management of acute myocardial
      infarction within Switzerland.
AB  - BACKGROUND: In Switzerland, health policies are decided at the local level, but
      little is known regarding their impact on the management of acute myocardial
      infarction (AMI). In this study, we assessed geographical differences within
      Switzerland regarding management of AMI. DESIGN: Cross-sectional study. METHODS:
      Swiss hospital discharge database for period 2007-2008 (26,204 discharges from
      AMI). Seven Swiss regions (Leman, Mittelland, Northwest, Zurich, Central,
      Eastern, and Ticino) were analysed. RESULTS: Almost 53.7% of discharges from AMI
      were managed in a single hospital, ranging from 62.1% (Leman) to 31.6% (Ticino).
      The highest intensive care unit admission rate was in Leman (69.4%), the lowest
      (16.9%) in Ticino (Swiss average: 36.0%). Intracoronary revascularization rates
      were highest in Leman (51.1%) and lowest (30.9%) in Central Switzerland (average:
      41.0%). Bare (non-drug-eluting) stent use was highest in Leman (61.4%) and lowest
      (16.9%) in Ticino (average: 42.1%), while drug-eluting stent use was highest
      (83.2%) in Ticino and lowest (38.6%) in Leman (average: 57.9%). Coronary artery
      bypass graft rates were highest (4.8%) in Ticino and lowest (0.5%) in Eastern
      Switzerland (average: 2.8%). Mechanical circulatory assistance rates were highest
      (4.2%) in Zurich and lowest (0.5%) in Ticino (average: 1.8%). The differences
      remained after adjusting for age, single or multiple hospital management, and
      gender. CONCLUSIONS: In Switzerland, significant geographical differences in
      management and revascularization procedures for AMI were found.

PMID- 23169866
TI  - Post-implantation mortality of in vitro produced embryos is associated with DNA
      methyltransferase 1 dysfunction in sheep placenta.
AB  - STUDY QUESTION: Is DNA methyltransferase 1 (DNMT1) dysfunction involved in
      epigenetic deregulation of placentae from embryos obtained by assisted
      reproduction technologies (ARTs)? SUMMARY ANSWER: DNMT1 expression in growing
      placentae of in vitro produced (IVP) embryos is compromised and associated with
      pregnancy loss. WHAT IS KNOWN ALREADY: DNMT1 maintains the methylation profile of
      genes during cell division. The methylation status of genes involved in placenta
      development is altered in embryos obtained in vitro. Disturbances in the
      epigenetic regulation of gene expression during placentogenesis could be involved
      in the frequent developmental arrest and loss of IVP embryos. STUDY DESIGN, SIZE,
      DURATION: Forty sheep were naturally mated (Group 1, CTR). IVP blastocysts (2-4
      per ewe) were surgically transferred to the remaining 46 recipient sheep 6 days
      after oestrus (Group 2). Twenty-one recipients from Group 1 and 27 recipients
      from Group 2 were allowed to deliver in order to compare embryo survival in both
      groups at term (150 days). From the remaining recipients (n = 38), fetuses and
      placentae of both groups were recovered by paramedian laparotomy at Days 20, 22,
      24, 26 and 28 of gestation. MATERIALS, SETTING, METHODS: Immediately after
      collection, early placental tissues (chorion-allantois) were snap frozen in
      liquid nitrogen and DNMT1 expression and activity was evaluated. mRNA levels (for
      DNMT1, HDAC2, PCNA, DMAP1, MEST, IGF2, CDKN1C, H19) and the methylation status of
      H19 were also analyzed. Furthermore, embryo size and survival rate were measured.
      MAIN RESULTS AND THE ROLE OF CHANCE: Our study shows that DNMT1 expression was
      reduced in early placentae from sheep IVP embryos. This reduction was associated
      with growth arrest and subsequent death of the sheep embryos. Conversely, normal
      levels of DNMT1 and its cofactors were observed in placentae from IVP embryos
      that survived this developmental bottleneck. Although DNA methylation machinery
      was severely compromised in IVP placentae only up to Day 24, the low DNMT1
      enzymatic activity that persisted after this stage in IVP placentae was not
      lethal for the developing embryos. LIMITATIONS, REASONS FOR CAUTION: The studied
      genes represent only a small fraction of genes regulating DNA methylation.
      Further studies are needed to evaluate changes in the expression and methylation
      status of other genes that may lead to developmental arrest of IVP embryos. As
      this is the only study evaluating the functionality of DNMT1 machinery in
      placentae from ART embryos, studies on other species are needed to confirm if our
      observation may be applicable to all mammalian embryos produced in vitro. WIDER
      IMPLICATIONS OF THE FINDINGS: The knowledge about compromised activity of DNMT1
      in placentae obtained from IVP embryos should stimulate detailed studies on the
      metabolic requirements of oocytes and embryos in order to adequately enrich the
      culture media.

PMID- 23169867
TI  - Embryos whose polar bodies contain isolated reciprocal chromosome aneuploidy are
      almost always euploid.
AB  - STUDY QUESTION: When a chromosome aneuploidy is detected in the first polar body
      and a reciprocal loss or gain of the same chromosome is detected in the second
      polar body, is the resulting embryo usually aneuploid for that chromosome?
      SUMMARY ANSWER: When reciprocal aneuploidy occurs in polar bodies, the resulting
      embryo is usually normal for that chromosome, indicating that premature
      separation of sister chromatids (PSSC)-not non-disjunction-likely occurred in
      meiosis I. WHAT IS KNOWN ALREADY: Single-nucleotide polymorphism-based microarray
      analysis can be used to accurately determine the chromosomal status of polar
      bodies and embryos. Sometimes, the only abnormality found is a reciprocal gain or
      loss of one or two chromosomes in the two polar bodies. Prediction of the status
      of the resulting embryo in these cases is problematic. STUDY DESIGN, SIZE,
      DURATION: Blinded microarray analysis of previously diagnosed aneuploid embryos
      that had reciprocal polar body aneuploidy. MATERIALS, SETTING, METHODS: IVF
      cycles were performed between 2008 and 2011 in patients aged 40 +/- 3 years
      (range 35-47 years) with an indication for polar body-based aneuploidy screening.
      Thirty-five aneuploid vitrified Day 3 embryos were warmed, cultured to Day 5 and
      biopsied for microarray analysis. Predictions were made for the ploidy status of
      the embryo if PSSC or non-disjunction had occurred. The signal intensity for the
      aneuploid chromosome in the first polar body was compared between those that
      resulted in euploid and aneuploid embryos. MAIN RESULTS AND THE ROLE OF CHANCE:
      Among 34 embryos with evaluable results, 31 were euploid on re-analysis. Of 43
      chromosomes that had reciprocal aneuploidy in the polar bodies, 41 were disomic
      in the embryo, indicating that PSSC was likely to have occurred 95% (95%
      confidence interval 85-99%) of the time. The log 2 ratio signal intensity from
      the chromosomes that underwent non-disjunction, resulting in unbalanced embryos,
      were outliers when compared with those that underwent PSSC. LIMITATIONS, REASONS
      FOR CAUTION: Although most embryos with reciprocal aneuploid polar bodies were
      euploid, it is unknown whether they maintain equivalent reproductive potential
      when transferred. Further study is needed to determine whether these embryos
      should be re-biopsied and considered for transfer. WIDER IMPLICATIONS OF THE
      FINDINGS: This study is consistent with increasing evidence that PSSC is the
      primary cause of meiosis I errors in embryos from women of advanced reproductive
      age. Clinicians should be cautious in interpreting results from polar body
      aneuploidy screening, especially when only the first polar body is tested.

PMID- 23169868
TI  - General health checks in adults for reducing morbidity and mortality from
      disease: Cochrane systematic review and meta-analysis.
AB  - OBJECTIVES: To quantify the benefits and harms of general health checks in adults
      with an emphasis on patient-relevant outcomes such as morbidity and mortality
      rather than on surrogate outcomes. DESIGN: Cochrane systematic review and meta
      analysis of randomised trials. For mortality, we analysed the results with random
      effects meta-analysis, and for other outcomes we did a qualitative synthesis as
      meta-analysis was not feasible. DATA SOURCES: Medline, EMBASE, Healthstar,
      Cochrane Library, Cochrane Central Register of Controlled Trials, CINAHL, EPOC
      register, ClinicalTrials.gov, and WHO ICTRP, supplemented by manual searches of
      reference lists of included studies, citation tracking (Web of Knowledge), and
      contacts with trialists. SELECTION CRITERIA: Randomised trials comparing health
      checks with no health checks in adult populations unselected for disease or risk
      factors. Health checks defined as screening general populations for more than one
      disease or risk factor in more than one organ system. We did not include
      geriatric trials. DATA EXTRACTION: Two observers independently assessed
      eligibility, extracted data, and assessed the risk of bias. We contacted authors
      for additional outcomes or trial details when necessary. RESULTS: We identified
      16 trials, 14 of which had available outcome data (182,880 participants). Nine
      trials provided data on total mortality (11,940 deaths), and they gave a risk
      ratio of 0.99 (95% confidence interval 0.95 to 1.03). Eight trials provided data
      on cardiovascular mortality (4567 deaths), risk ratio 1.03 (0.91 to 1.17), and
      eight on cancer mortality (3663 deaths), risk ratio 1.01 (0.92 to 1.12). Subgroup
      and sensitivity analyses did not alter these findings. We did not find beneficial
      effects of general health checks on morbidity, hospitalisation, disability,
      worry, additional physician visits, or absence from work, but not all trials
      reported on these outcomes. One trial found that health checks led to a 20%
      increase in the total number of new diagnoses per participant over six years
      compared with the control group and an increased number of people with self
      reported chronic conditions, and one trial found an increased prevalence of
      hypertension and hypercholesterolaemia. Two out of four trials found an increased
      use of antihypertensives. Two out of four trials found small beneficial effects
      on self reported health, which could be due to bias. CONCLUSIONS: General health
      checks did not reduce morbidity or mortality, neither overall nor for
      cardiovascular or cancer causes, although they increased the number of new
      diagnoses. Important harmful outcomes were often not studied or reported.
      SYSTEMATIC REVIEW REGISTRATION: Cochrane Library, doi:10.1002/14651858.CD009009.

PMID- 23169869
TI  - Muscular strength in male adolescents and premature death: cohort study of one
      million participants.
AB  - OBJECTIVES: To explore the extent to which muscular strength in adolescence is
      associated with all cause and cause specific premature mortality (<55 years).
      DESIGN: Prospective cohort study. SETTING: Sweden. PARTICIPANTS: 1,142,599
      Swedish male adolescents aged 16-19 years were followed over a period of 24
      years. MAIN OUTCOME MEASURES: Baseline examinations included knee extension,
      handgrip, and elbow flexion strength tests, as well as measures of diastolic and
      systolic blood pressure and body mass index. Cox regression was used to estimate
      hazard ratios for mortality according to muscular strength categories (tenths).
      RESULTS: During a median follow-up period of 24 years, 26,145 participants died.
      Suicide was a more frequent cause of death in young adulthood (22.3%) than was
      cardiovascular diseases (7.8%) or cancer (14.9%). High muscular strength in
      adolescence, as assessed by knee extension and handgrip tests, was associated
      with a 20-35% lower risk of premature mortality due to any cause or
      cardiovascular disease, independently of body mass index or blood pressure; no
      association was observed with mortality due to cancer. Stronger adolescents had a
      20-30% lower risk of death from suicide and were 15-65% less likely to have any
      psychiatric diagnosis (such as schizophrenia and mood disorders). Adolescents in
      the lowest tenth of muscular strength showed by far the highest risk of mortality
      for different causes. All cause mortality rates (per 100,000 person years) ranged
      between 122.3 and 86.9 for the weakest and strongest adolescents; corresponding
      figures were 9.5 and 5.6 for mortality due to cardiovascular diseases and 24.6
      and 16.9 for mortality due to suicide. CONCLUSIONS: Low muscular strength in
      adolescents is an emerging risk factor for major causes of death in young
      adulthood, such as suicide and cardiovascular diseases. The effect size observed
      for all cause mortality was equivalent to that for well established risk factors
      such as elevated body mass index or blood pressure.

PMID- 23169871
TI  - The value of conducting periodic health checks.

PMID- 23169870
TI  - Sharing of clinical trial data among trialists: a cross sectional survey.
AB  - OBJECTIVE: To investigate clinical trialists' opinions and experiences of sharing
      of clinical trial data with investigators who are not directly collaborating with
      the research team. DESIGN AND SETTING: Cross sectional, web based survey.
      PARTICIPANTS: Clinical trialists who were corresponding authors of clinical
      trials published in 2010 or 2011 in one of six general medical journals with the
      highest impact factor in 2011. MAIN OUTCOME MEASURES: Support for and prevalence
      of data sharing through data repositories and in response to individual requests,
      concerns with data sharing through repositories, and reasons for granting or
      denying requests. RESULTS: Of 683 potential respondents, 317 completed the survey
      (response rate 46%). In principle, 236 (74%) thought that sharing de-identified
      data through data repositories should be required, and 229 (72%) thought that
      investigators should be required to share de-identified data in response to
      individual requests. In practice, only 56 (18%) indicated that they were required
      by the trial funder to deposit the trial data in a repository; of these 32 (57%)
      had done so. In all, 149 respondents (47%) had received an individual request to
      share their clinical trial data; of these, 115 (77%) had granted and 56 (38%) had
      denied at least one request. Respondents' most common concerns about data sharing
      were related to appropriate data use, investigator or funder interests, and
      protection of research subjects. CONCLUSIONS: We found strong support for sharing
      clinical trial data among corresponding authors of recently published trials in
      high impact general medical journals who responded to our survey, including a
      willingness to share data, although several practical concerns were identified.

PMID- 23169872
TI  - The new BMJ policy on sharing data from drug and device trials.

PMID- 23169873
TI  - Obtaining surrogate consent for a minimal-risk research study in the intensive
      care unit setting.
AB  - BACKGROUND: Obtaining surrogate consent for clinical research studies conducted
      in the intensive care unit (ICU) setting is logistically challenging. PURPOSE: To
      determine whether differences in proportions consenting to trial enrollment
      existed among patients eligible to consent directly versus those requiring
      surrogate decision makers in a minimal-risk study to evaluate the accuracy of
      continuous glucose monitoring in the ICU setting. METHODS: Low initial enrollment
      rates prompted a detailed tracking of the screening and consent process. We
      analyzed the subset of eligible patients identified during a single year to
      document whether they were approached about trial enrollment, whether they
      consented or declined, the reasons for declining, and the method of consent (self
      or surrogate). The proportion of participants who consented and the reasons for
      declining were compared for self-consenting and surrogate-consenting
      participants. RESULTS: Of the 3041 patients screened, one-third (n = 982) were
      eligible; 119 of the 982 were approached regarding enrollment. Absence of a
      surrogate accounted for the majority of eligible patients (726; 84%) not
      approached. The most common reasons for refusal in the self versus surrogate
      groups included feeling overwhelmed (13% vs 24%), fear of discomfort (22% vs
      12%), and fear of risk (7% vs 4%). Of the 57 eligible patients capable of
      consenting directly, 11 (19%) enrolled versus 12 (19%) of the 62 who required
      surrogate consent. When recruitment hours were expanded to include evening time,
      more eligible patients or their surrogates could be approached than during the
      day-shift hours alone. Consent was obtained for a larger proportion of potential
      participants with a history of diabetes (40%) than for those without a history of
      diabetes (14%). LIMITATIONS: The findings are from a subset of the entire study
      sample; data were available only for participants who could be approached, who
      may have differed from those who could not be approached. CONCLUSIONS: Surrogate
      and self-consent rates were similar. Surrogate unavailability was a major barrier
      to enrollment; overlap of staffing with usual visiting hours should be considered
      when planning trials in the ICU.

PMID- 23169874
TI  - Development of the Stanford Expectations of Treatment Scale (SETS): a tool for
      measuring patient outcome expectancy in clinical trials.
AB  - BACKGROUND: A patient's response to treatment may be influenced by the
      expectations that the patient has before initiating treatment. In the context of
      clinical trials, the influence of participant expectancy may blur the distinction
      between real and sham treatments, reducing statistical power to detect specific
      treatment effects. There is therefore a need for a tool that prospectively
      predicts expectancy effects on treatment outcomes across a wide range of
      treatment modalities. PURPOSE: To help assess expectancy effects, we created the
      Stanford Expectations of Treatment Scale (SETS): an instrument for measuring
      positive and negative treatment expectancies. Internal reliability of the
      instrument was tested in Study 1. Criterion validity of the instrument
      (convergent, discriminant, and predictive) was assessed in Studies 2 and 3.
      METHODS: The instrument was developed using 200 participants in Study 1.
      Reliability and validity assessments were made with an additional 423
      participants in Studies 2 and 3. RESULTS: The final six-item SETS contains two
      subscales: positive expectancy (alpha = 0.81-0.88) and negative expectancy (alpha
      = 0.81-0.86). The subscales predict a significant amount of outcome variance
      (between 12% and 18%) in patients receiving surgical and pain interventions. The
      SETS is simple to administer, score, and interpret. CONCLUSION: The SETS may be
      used in clinical trials to improve statistical sensitivity for detecting
      treatment differences or in clinical settings to identify patients with poor
      treatment expectancies.

PMID- 23169875
TI  - Assessment of haematological parameters in HIV-infected and uninfected Rwandan
      women: a cross-sectional study.
AB  - OBJECTIVES: Although haematological abnormalities are common manifestations of
      HIV infection, few studies on haematological parameters in HIV-infected persons
      have been undertaken in sub-Saharan Africa. The authors assessed factors
      associated with haematological parameters in HIV-infected antiretroviral-naive
      and HIV-uninfected Rwandan women. STUDY DESIGN: Cross-sectional analysis of a
      longitudinal cohort. SETTING: Community-based women's associations. PARTICIPANTS:
      710 HIV-infected (HIV+) antiretroviral-naive and 226 HIV-uninfected (HIV-) women
      from the Rwanda Women's Interassociation Study Assessment. Haematological
      parameters categorised as (abnormal vs normal) were compared by HIV status and
      among HIV+ women by CD4 count category using proportions. Multivariate logistic
      regression models using forward selection were fit. RESULTS: Prevalence of
      anaemia (haemoglobin (Hb) <12.0 g/dl) was higher in the HIV+ group (20.5% vs
      6.3%; p<0.001), and increased with lower CD4 counts: >=350 (7.6%), 200-349 (16%)
      and <200 cells/mm(3) (32.2%). Marked anaemia (Hb <10.0 g/dl) was found in 4.2% of
      HIV+ and none of the HIV- women (p<0.001), and was highest in HIV+ women with CD4
      <200 cells/mm(3) (8.4%). The HIV+ were more likely than HIV- women (4.2 vs 0.5%,
      respectively, p=0.002) to have moderate neutropenia with white blood cells
      <2.0*10(3) cells/mm(3) and 8.4% of HIV+ women with CD4 <200 cells/mm(3) had
      moderate neutropenia. In multivariate logistic regression analysis, BMI (OR
      0.87/kg/m(2), 95% CI 0.82 to 0.93; p<0.001), CD4 200-350 vs HIV- (OR 3.59, 95% CI
      1.89 to 6.83; p<0.001) and CD4 <200 cells/mm(3) vs HIV- (OR 8.09, 95% CI 4.37 to
      14.97; <0.001) had large independent associations with anaemia. There were large
      independent associations of CD4 <200 cells/mm(3) vs HIV- (OR 7.18, 95% CI 0.78 to
      65.82; p=0.081) and co-trimoxazole and/or dapsone use (OR 5.69, 95% CI 0.63 to
      51.45; p=0.122) with moderate neutropenia. CONCLUSIONS: Anaemia was more common
      than neutropenia or thrombocytopenia in the HIV-infected Rwandan women. Future
      comparisons of haematological parameters in HIV-infected patients before and
      after antiretroviral therapy initiation are warranted.

PMID- 23169876
TI  - Reconstruction of aorto-mitral continuity with a handmade aorto-mitral
      bioprosthetic valve for extensive bivalvular endocarditis.
AB  - Surgical treatment is effective to exclude all infected tissue in patients with
      infective endocarditis. Although various techniques have been reported, it has
      remained a great challenge for patients with extensive infected regions. A
      patient with extensive bivalvular endocarditis including the aortic and mitral
      valve and aorto-mitral continuity is described. A handmade aorto-mitral
      bioprosthetic valve was created to reconstruct the defect after extensive
      debridement. The patient was discharged on the 30th postoperative day without
      inflammatory signs.

PMID- 23169877
TI  - Video-assisted thoracic surgery versus open thoracotomy for non-small cell lung
      cancer: a meta-analysis of propensity score-matched patients.
AB  - OBJECTIVES: This meta-analysis aimed to compare the perioperative outcomes of
      video-assisted thoracic surgery (VATS) with open thoracotomy for propensity score
      matched patients with early-stage non-small cell lung cancer (NSCLC). METHODS:
      Four relevant studies with propensity score-matched patients were identified from
      six electronic databases. Endpoints included perioperative mortality and
      morbidity, individual postoperative complications and duration of
      hospitalization. RESULTS: Results indicate that all-cause perioperative mortality
      was similar between VATS and open thoracotomy. However, patients who underwent
      VATS were found to have significantly fewer overall complications, and
      significantly lower rates of prolonged air leak, pneumonia, atrial arrhythmias
      and renal failure. In addition, patients who underwent VATS had a significantly
      shorter length of hospitalization compared with those who underwent open
      thoracotomy. CONCLUSIONS: In view of a paucity of high-level clinical evidence in
      the form of large, well-designed randomized controlled trials, propensity score
      matching may provide the highest level of evidence to compare VATS with open
      thoracotomy for patients with NSCLC. The present meta-analysis demonstrated
      superior perioperative outcomes for patients who underwent VATS, including
      overall complication rates and duration of hospitalization.

PMID- 23169878
TI  - Does surgery improve prognosis in patients with small-cell lung carcinoma?
AB  - A best evidence topic was written according to a structured protocol, asking
      'does surgery improve prognosis in patients with small-cell lung carcinoma
      (SCLC)?' One hundred and thirteen papers were identified, of which the nine
      papers best able to answer the question were selected and the details of each
      tabulated. The prohibitive attitude of clinicians toward surgery in SCLC has
      prevailed since the 1960s, informed by a prospective randomized trial in which
      144 patients were assigned to surgical treatment or to radical radiotherapy.
      Surgery conferred no survival benefit when compared with radical radiotherapy as
      assessed at 6 monthly intervals up to 10 years post-treatment. Patients with
      metastatic disease were excluded; however, diagnostic advances subsequent to
      these trials justify a re-evaluation of the issue, given the greater degree of
      accuracy with which sub-groups of patients who might benefit from surgery can now
      be defined. Only one further prospective, randomized trial features in the
      literature. This study also discerned that no survival benefit was accrued by
      adding surgery to chemotherapy. However, this study only included patients who
      responded to an initial course of chemotherapy and also excluded patients with
      peripheral nodules only. Subsequent investigators have asserted the value of
      surgery in SCLC. A retrospective case-control study found that surgery
      significantly improved median survival in patients with stage I disease when
      compared with patients undergoing medical therapy. One British centre reported
      survival rates of 52% at 5 years amongst patients undergoing resection and nodal
      dissection for stage II-IIIA disease. In a retrospective analysis of the
      Norwegian cancer database, 5-year survival for patients with stage I undergoing
      surgery was 44.9%, as opposed to 11.3% amongst those treated medically. This
      finding was echoed in the analysis of the surveillance epidemiology and end
      results database in the USA, which found improved median survival amongst
      patients undergoing surgery for limited SCLC. Prospective studies of carefully
      selected patients have documented good median survival in patients whose tumour
      was completely resected. We conclude that surgery for early-stage SCLC improves
      prognosis as part of a multi-modality approach. This echoes the advice of the
      2011 national institute of health and clinical excellence guidelines regarding
      surgery in SCLC.

PMID- 23169879
TI  - Lung metastasis caused by an infection with Echinococcus alveolaris.
AB  - Echinococcus alveolaris (E. alveolaris) (multi-localaris) is a parasitic agent
      that commonly affects the liver and poses as a solid mass. In contrast to
      Echnicoccus granulosus, E. alveolaris tends to invade adjacent structures rather
      than displace and compress them. Haematogenous dissemination to other organs such
      as the lungs, brain, or bone is rare. In this case, we report on a 34-year old
      woman with a history of liver segmentectomy due to E. alveolaris infestation and
      the disease disseminated to the lungs. Computed tomography and magnetic resonance
      imaging showed multiple opacities and mixed signal intensities in the lungs,
      mimicking metastatic disease. The biopsy proved that the lesions were a result of
      metastasis of E. alveolaris.

PMID- 23169880
TI  - Early loss of innervation of cornea epithelium in streptozotocin-induced type 1
      diabetic rats: improvement with ilepatril treatment.
AB  - PURPOSE: Cornea confocal microscopy is emerging as a clinical tool to evaluate
      the development and progression of diabetic neuropathy. The purpose of these
      studies was to characterize the early changes in corneal sensitivity and
      innervation in a rat model of type 1 diabetes in relation to standard peripheral
      neuropathy endpoints and to assess the effect of Ilepatril, a vasopeptidase
      inhibitor which blocks angiotensin converting enzyme and neutral endopeptidase,
      on these endpoints. METHODS: Streptozotocin-diabetic rats 8 weeks duration were
      treated with or without Ilepatril for the last 6 weeks of the experimental
      period. Afterwards, standard diabetic neuropathy endpoints, subbasal corneal
      nerves and innervation of the epithelium, corneal sensitivity using a Cochet
      Bonnet esthesiometer, and vascular reactivity of the posterior ciliary artery
      were examined. RESULTS: Diabetes caused a decrease in nerve conduction velocity,
      thermal hypoalgesia, and a reduction in intraepidermal nerve fiber profiles. In
      the cornea there was a decrease in corneal nerve fibers innervating the
      epithelium and corneal sensitivity, but subbasal corneal nerve fibers was not
      changed. Vascular relaxation in response to acetylcholine was decreased in the
      posterior ciliary artery. These defects were partially to completely prevented by
      Ilepatril treatment. CONCLUSIONS: These studies suggest that in type 1 diabetic
      rats decreased innervation of the cornea epithelium occurs early in diabetes and
      prior to a detectable decrease in subbasal corneal nerves and that these and
      other diabetic neuropathy-related defects can be partially to completely
      prevented by a vasopeptidase inhibitor.

PMID- 23169881
TI  - Intracorneal ring segment in keratoconus: a model to predict visual changes
      induced by the surgery.
AB  - PURPOSE: We detected keratoconus cases with a significant potential for poor
      outcomes following intracorneal ring segment implantation (ICRS). We attempted to
      predict the potential of a case in terms of gain or loss of corrected distance
      visual acuity (CDVA). METHODS: In this retrospective and prospective,
      consecutive, nonrandomized, multicentric study, 58 keratoconic eyes (aged 1756)
      were implanted with the keraring using the femtosecond laser technology. The
      follow-up period was 6 months. keratometric, biomechanical, aberrometric,
      refractive, and visual variables were measured for two different groups: Group A
      included eyes that gained 0.2 or more in corrected distance visual acuity (CDVA,
      decimal scale) and group B included eyes that lost more than 0.15. Correlations
      between clinical parameters and changes in visual acuity were investigated. In
      addition, a linear regression model was developed using CDVA, apical keratometry
      (AK), and a new keratometric parameter defined and named by us as K-factor
      (K(F)). RESULTS: Significant differences between groups preoperatively were found
      for CDVA (P = 0.002), AK (P = 0.013), and K(F) (P = 0.025). The following
      predictive model was obtained using these variables: DeltaCDVA = -0.511 +
      0.0007K(F)(p)-0.849CDVA(p)+0.008AK(p).$$ Predictability of the model was 0.797.
      Sensitivity was 88.1% and specificity 83.3%. CONCLUSIONS: The mathematical model
      predicts that this surgery is very effective in patients with preoperative CDVA
      (decimal scale) in the range of 0.01 to 0.3, predicting a gain of 3, 4, or even 5
      lines. Gains are predicted and confirmed for CDVA between 0.3 and 0.5. For
      preoperative CDVA between 0.5 and 0.75 visual outcomes are doubtful. Higher
      values of CDVA often are related to a decrease in CDVA. This model may help
      surgeons to select the best cases for ICRS implantation and exclude the worst in
      terms of visual outcomes.

PMID- 23169883
TI  - Quantitative evaluation of factors influencing the repeatability of SD-OCT
      thickness measurements in the rat.
AB  - PURPOSE: To quantify repeatability and reproducibility of thickness measurements
      and the effects of realignment and image quality on measurements of retinal
      thickness from optical coherence tomographic (OCT) imaging in the rat eye.
      METHODS: Retinal imaging was performed in 16 brown norway rats (N = 16 EYES; X =
      372 G). Precision metrics: 95% limits of agreement (LoA), intraclass correlation
      coefficient (ICC), and the coefficient of variation (CV), were calculated using
      manual and combined manual + automated realignment procedures for nerve fiber and
      retinal ganglion cell layer (NFL/GCL), NFL/GCL and inner plexiform layer (NFL/GCL
      + IPL), and total retina thicknesses (excluding blood vessels). The influence of
      image quality on NFL thickness measurement was assessed by comparing high- and
      low-quality image data (real and simulated) from the rat as well as clinical
      data. RESULTS: Mean NFL/GCL thickness was 26 3 M, NFL/GCL + IPL thickness was 70
      3 M, AND total retinal thickness was 192 7 M. Thickness difference between
      imaging sessions for NFL/GCL was 1 M (95% LOA: -4 to 3 MUm; ICC = 0.82; CV =
      4.7%), for NFL/GCL + IPL was 0 MUm (95% LoA: -4 to 4 MUm; ICC = 0.88; CV = 1.4%),
      and total retinal thickness was 1 MUm (95% LoA: -3 to 4 MUm; ICC = 0.97; CV =
      0.7%). Thickness differences were similar between realignment procedures
      (NFL/GCL: P = 0.43; NFL/GCL + IPL: P = 0.33; total retina: P = 0.62). Although
      NFL thickness measurements increased slightly in low-quality rat images (4 MUm; P
      = 0.04), this was not true with clinical images (1.4 MUm; P = 0.36). CONCLUSIONS:
      Precision of retinal layer thickness estimation from OCT imaging is excellent
      when manual and automated realignment procedures are combined, but may still be
      influenced by image quality and segmentation methods.

PMID- 23169882
TI  - Ocular surface extracellular DNA and nuclease activity imbalance: a new paradigm
      for inflammation in dry eye disease.
AB  - PURPOSE: We determined whether nucleases are deficient in the tear fluid of dry
      eye disease (DED) patients, and whether this causes extracellular DNA (eDNA) and
      neutrophil extracellular trap (NET) accumulation in the precorneal tear film,
      thus causing ocular surface inflammation. METHODS: Exfoliated cells adhered to
      Schirmer test strips were collected on glass slides, and immunofluorescence
      confocal microscopy was used to evaluate neutrophils, eDNA, NETs, and their
      molecular components. Similar experiments were performed with mucoid films
      collected from the inferior conjunctival fornix or bulbar conjunctiva. We used
      quantitative PCR to evaluate eDNA signaling pathways and inflammatory cytokine
      expression. We also determined the amount of ocular surface eDNA and evaluated
      tear fluid nuclease activity. RESULTS: eDNA, NETs, and neutrophils were present
      on the ocular surface in DED patients and abundant in mucoid films. NETs
      consisted of eDNA, histones, cathelicidin, and neutrophil elastase. Tear fluid
      nuclease activity was decreased significantly in DED patients, whereas the amount
      of eDNA on the ocular surface was increased significantly. Expression of genes
      downstream of eDNA signaling, such as TLR9, MyD88, and type I interferon, as well
      as the inflammatory cytokines interleukin-6 and tumor necrosis factor-alpha, was
      significantly increased in DED patients. CONCLUSIONS: Extracellular DNA
      production and clearance mechanisms are dysregulated in DED. Nuclease deficiency
      in tear fluid allows eDNA and NETs to accumulate in precorneal tear film, and
      results in ocular surface inflammation. These findings point to novel therapeutic
      interventions in severe DED based on clearance of eDNA, NETs, and other molecular
      components from the ocular surface.

PMID- 23169884
TI  - Topical pazopanib blocks VEGF-induced vascular leakage and neovascularization in
      the mouse retina but is ineffective in the rabbit.
AB  - PURPOSE: To test the effect of pazopanib, a tyrosine kinase inhibitor that blocks
      VEGF and platelet-derived growth factor (PDGF) receptors and c-Kit, on vascular
      leakage and neovascularization (NV) in the retina. METHODS: Pazopanib was tested
      to determine its effect on VEGF-induced vascular permeability via measurement of
      [(3)H]mannitol retina to lung (RLLR) and retina to renal leakage ratios (RRLR)
      and in rho/VEGF mice with subretinal NV. In rabbits, the effect of intravitreal,
      topical, and systemic pazopanib on VEGF-induced leakage was tested by vitreous
      fluorophotometry. RESULTS: In mice, oral pazopanib (40 mg/kg twice a day [bid])
      reduced RLLR (0.84 to 0.58, P = 0.0014) and RRLR (0.55 to 0.30, P = 0.0018) in
      VEGF-injected eyes. After intraocular injection of VEGF into both eyes, topical
      pazopanib (10 mg/mL three times a day [tid] for 14 days) reduced RLLR (0.85 vs.
      0.56, P = 0.001), RRLR (0.44 vs. 0.28, P = 0.0075), and immunoreactive albumin in
      the retina compared to values in fellow eye controls. Treatment of one eye of
      rho/VEGF mice with 10 mg/mL, but not 5 mg/mL, pazopanib tid reduced the mean area
      of subretinal NV compared to that in fellow eyes (0.0055 vs. 0.0025 mm(2), P =
      0.020). In rabbits, intravitreal pazopanib suppressed VEGF-induced fluorescein
      leakage, but topical (10 mg/mL four times a day [qid] or 12 mg/mL bid) had no
      significant effect. Systemic administration of pazopanib by osmotic pump with or
      without 10 mg/mL drops tid also failed to suppress VEGF-induced leakage.
      CONCLUSIONS: Administration of pazopanib topically or systemically suppressed
      retinal vascular leakage in mice, but not rabbits. These data suggest differences
      in the blood-retinal barrier (BRB) of mice and rabbits and indicate that
      penetration through the outer BRB may be needed for topically administered drugs
      to exert effects in the retina.

PMID- 23169885
TI  - Loss of Hfe leads to progression of tumor phenotype in primary retinal pigment
      epithelial cells.
AB  - PURPOSE: Hemochromatosis is a disorder of iron overload arising mostly from
      mutations in HFE. HFE is expressed in retinal pigment epithelium (RPE), and Hfe(
      /-) mice develop age-related iron accumulation and retinal degeneration
      associated with RPE hyperproliferation. Here, the mechanism underlying the
      hyperproliferative phenotype in RPE was investigated. METHODS: Cellular
      senescence was monitored by beta-galactosidase activity. Gene expression was
      monitored by real-time PCR. Survivin was analyzed by Western blot and
      immunofluorescence. Migration and invasion were monitored using appropriate kits.
      Glucose transporters (GLUTs) were monitored by 3-O-methyl-D-glucose uptake.
      Histone deacetylases (HDACs) were studied by monitoring catalytic activity and
      acetylation status of histones H3/H4. RESULTS: Hfe(-/-) RPE cells exhibited
      slower senescence rate and higher survivin expression than wild type cells. Hfe(
      /-) cells migrated faster and showed greater glucose uptake and increased
      expression of GLUTs. The expression of HDACs and DNA methyltransferase (DNMTs)
      also was increased. Similarly, RPE cells from hemojuvelin (Hjv)-knockout mice,
      another model of hemochromatosis, also had increased expression of GLUTs, HDACs,
      and DNMTs. The expression of Slc5a8 was decreased in Hfe(-/-) RPE cells, but
      treatment with a DNA methylation inhibitor restored the transporter expression,
      indicating involvement of DNA methylation in the silencing of Slc5a8 in Hfe(-/-)
      cells. CONCLUSIONS: RPE cells from iron-overloaded mice exhibit several features
      of tumor cells: decreased senescence, enhanced migration, increased glucose
      uptake, and elevated levels of HDACs and DNMTs. These features are seen in Hfe(-/
      ) RPE cells as well as in Hjv(-/-) RPE cells, providing a molecular basis for the
      hyperproliferative phenotype of Hfe(-/-) and Hjv(-/-) RPE cells.

PMID- 23169887
TI  - Topographical distribution of retinal and optic disc neovascularization in early
      stages of proliferative diabetic retinopathy.
AB  - PURPOSE: We analyzed the topography of proliferative diabetic retinopathy (PDR),
      and visualized the distribution of neovascularization of the optic disc (NVD) and
      elsewhere in the retina (NVE). METHODS: The study included 174 eyes of 106
      patients with early PDR. Data on the size and location of 391 NVE and 73 NVD were
      converted into a database of two-dimensional retinal and optic disc charts. The
      geometric centers of the neovascular lesions were plotted into corresponding
      areas of the charts, and the topographic distributions of the NVE and NVD were
      visualized by merging the charts and displaying the number of overlapping lesions
      on color-coded contour maps. RESULTS: A total of 141 (36%) NVE was located in the
      temporal and 250 (64%) in the nasal hemisphere (P < 0.0001). The distribution of
      the NVD in the temporal and nasal half of the optic disc was 46 (63%) and 27
      (37%), respectively (P = 0.03). NVE in type 1 diabetes were located significantly
      farther from the fovea and optic disc, and were more numerous and larger than in
      type 2 diabetes. The number and diameter of the NVE were also significantly
      higher when the time from the last examination to the appearance of PDR exceeded
      12 months. CONCLUSIONS: The majority of NVE lesions are located inferonasal to
      the optic disc and along the superior vascular arcades, while NVD have a
      predilection for the upper temporal disc rim. More extensive PDR is found in
      patients with type 1 diabetes and those with examination intervals longer than
      one year.

PMID- 23169886
TI  - Anterior and posterior optic nerve head blood flow in nonhuman primate
      experimental glaucoma model measured by laser speckle imaging technique and
      microsphere method.
AB  - PURPOSE: To characterize optic nerve head (ONH) blood flow (BF) changes in
      nonhuman primate experimental glaucoma (EG) using laser speckle flowgraphy (LSFG)
      and the microsphere method and to evaluate the correlation between the two
      methods. METHODS: EG was induced in one eye each of 9 rhesus macaques by laser
      treatment to the trabecular meshwork. Prior to lasering and following onset of
      intraocular pressure (IOP) elevation, retinal never fiber layer thickness (RNFLT)
      and ONH BF were measured biweekly by spectral-domain optical coherence tomography
      and LSFG, respectively, until RNFLT loss was approximately 40% in the EG eye.
      Final BF was measured by LSFG and by the microsphere method in the anterior ONH
      (MS-BF(ANT)), posterior ONH (MS-BF(POST)), and peripapillary retina (MS-BF(PP)).
      RESULTS: Baseline RNFLT and LSFG-BF showed no difference between the two eyes (P
      = 0.69 and P = 0.43, respectively, paired t-test). Mean (+/- SD) IOP was 30 +/- 6
      mm Hg in EG eyes and 13 +/- 2 mm Hg in control eyes (P < 0.001). EG eye RNFLT and
      LSFG-BF were reduced by 42 +/- 16% (P < 0.0001) and 22 +/- 13% (P = 0.003),
      respectively, at the final time point. EG eye MS-BF(ANT), MS-BF(POST), and MS
      BF(PP) were reduced by 41 +/- 17% (P < 0.001), 22 +/- 34% (P = 0.06), and 30 +/-
      12% (P = 0.001), respectively, compared with the control eyes. Interocular ONH
      LSFG-BF differences significantly correlated to that measured by the microsphere
      method (R(2) = 0.87, P < 0.001). CONCLUSIONS: Chronic IOP elevation causes
      significant ONH BF decreases in the EG model. The high correlation between the BF
      reduction measured by LSFG and the microsphere method provides evidence that the
      LSFG is capable of assaying BF for a critical deep ONH region.

PMID- 23169888
TI  - Simultaneous detection of Clavibacter michiganensis subsp. nebraskensis and
      Pantoea stewartii subsp. stewartii based on microsphere immunoreaction.
AB  - Clavibacter michiganensis subsp. nebraskensis (Cmn) and Pantoea stewartii subsp.
      stewartii (Pss) are two plant pathogens that can cause tremendous agricultural
      economic losses. This novel method based on microsphere immunoreaction was
      developed for the simultaneous detection of Cmn and Pss in maize. This multiplex
      method was constructed based on microsphere immunodetection with fluorescent
      labels such as quantum dots (QDs) and R-phycoerythrin (R-PE) for the detection of
      Cmn and Pss. Captured QDs and R-PE serve as signal reporters for fluorescent
      readout. The principle of this method is based on a sandwich immunoreaction. Cmn
      and Pss captured by the microspheres were detected using flow cytometry. The
      limit of detection of this method was 10 times lower than the enzyme-linked
      immunosorbent assay (ELISA), and its analysis time (1 h) was much shorter
      compared with ELISA (6-8 h). The method, which has been proven to be an effective
      approach to multiplex detection of plant bacteria (Cmn and Pss as models), not
      only increased the varieties but also improved the sensitivity. The microsphere
      immunoreaction provides a universal method for the multiplex determination of
      microbes because of its high sensitivity, specificity, and speed. In the future,
      the method will be more fully validated in vivo to detect diversiform bacteria.

PMID- 23169889
TI  - Tooth agenesis association with self-reported family history of cancer.
AB  - It has been proposed that tooth agenesis and cancer development share common
      molecular pathways. We performed a cross-sectional study to investigate the
      epidemiological and molecular association between tooth agenesis and self
      reported family history of cancer. Eighty-two individuals with tooth agenesis and
      328 individuals with no birth defect were recruited from the same institution.
      Tooth agenesis was assessed in permanent teeth and was defined based on the age
      of the participants and when initial tooth formation should be radiographically
      visible. We also investigated the role of genes involved in dental development
      that have been implicated in tumorigenesis, and 14 markers in AXIN2, FGF3, FGF10,
      and FGFR2 were genotyped. Individuals with tooth agenesis had an increased risk
      of having a family history of cancer (p = 0.00006; OR = 2.7; 95% C.I., 1.6-4.4).
      There were associations between AXIN2, FGF3, FGF10, and FGFR2 with tooth agenesis
      [i.e., individuals who carried the polymorphic allele of FGFR2 (rs1219648)
      presented higher risk for having premolar agenesis (p = 0.02; OR = 1.8; 95% C.I.,
      1.1-3.0)]. In conclusion, tooth agenesis was associated with positive self
      reported family history of cancer and with variants in AXIN2, FGF3, FGF10, and
      FGFR2. Prospective studies are needed to confirm if tooth agenesis can be used as
      a risk marker for cancer.

PMID- 23169890
TI  - Antimalarial activity of isoquine against Kenyan Plasmodium falciparum clinical
      isolates and association with polymorphisms in pfcrt and pfmdr1 genes.
AB  - BACKGROUND: The use of amodiaquine in prophylaxis is associated with serious
      toxicity, resulting from its metabolic conversion into a reactive quinone-imine
      metabolite by the hepatic cytochrome P450. To circumvent this toxicity, several
      amodiaquine analogues that lack the potential to form a quinone-imine derivative,
      while retaining antimalarial activity, have been designed. Isoquine is one of
      these promising molecules that has already reached Phase I clinical trials in
      humans. METHODS: We analysed the in vitro activity of isoquine against 62
      Plasmodium falciparum isolates collected in Kenya and the association of this
      activity with polymorphisms in pfcrt and pfmdr1 genes. RESULTS: The median
      concentration of isoquine that inhibited 50% of parasite growth (IC50) was 9 nM,
      compared with 56 nM chloroquine, 8 nM amodiaquine, 10 nM desethylamodiaquine, 69
      nM lumefantrine and 1 nM dihydroartemisinin. Isoquine activity was correlated
      with polymorphisms in pfcrt at codon 76, but not in pfmdr1 at codon 86.
      CONCLUSIONS: The high activity of isoquine against field isolates, including
      chloroquine-resistant isolates, with IC50 <10 nM, warrants its further
      development as an antimalarial.

PMID- 23169891
TI  - Macrolide-resistant Mycoplasma pneumoniae: its role in respiratory infection.
AB  - Although the clinical relevance of antibiotic treatment in influencing the
      natural course of Mycoplasma pneumoniae-associated respiratory diseases is
      questioned by some physicians, most experts suggest that antibiotics should be
      systematically used in patients with M. pneumoniae respiratory infections,
      especially those involving the lower respiratory tract. Macrolides (MLs),
      tetracyclines (TCs) and fluoroquinolones (FQs) are the drugs of choice for M.
      pneumoniae infection, but only MLs are recommended for children. The main aim of
      this review is to analyse what is known about M. pneumoniae resistance to MLs and
      discuss the most reasonable approach to treating patients with M. pneumoniae
      infection at a time when resistant strains are being increasingly detected. The
      results show that no change in ML prescription is needed in countries in which
      the incidence of ML-resistant M. pneumoniae is low; however, in countries in
      which ML-resistant M. pneumoniae strains are very common, the replacement of an
      ML by a TC or FQ should be considered depending on the severity of the disease. A
      number of cases treated with ineffective antibiotics have shown similar outcomes
      to those observed in patients infected by susceptible strains. This seems to
      indicate that there is no need to change ML use systematically in the case of
      mild to moderate disease, but other antibiotics should be prescribed if the
      symptoms persist or there are signs of a clinical deterioration.

PMID- 23169892
TI  - A novel family of genomic resistance islands, AbGRI2, contributing to
      aminoglycoside resistance in Acinetobacter baumannii isolates belonging to global
      clone 2.
AB  - OBJECTIVES: To determine the context and location of antibiotic resistance genes
      in carbapenem- and aminoglycoside-resistant Acinetobacter baumannii global clone
      2 (GC2) isolates carrying a class 1 integron. METHODS: Isolates were from Sydney
      hospitals. Resistance to antibiotics was determined by disc diffusion. BLAST
      searches identified relevant DNA fragments in a draft genome sequence. PCR was
      used to assemble fragments and map equivalent regions. RESULTS: In two isolates
      belonging to GC2, WM99c and A91, the bla(TEM) gene, the class 1 integron carrying
      the aacC1-orfP-orfP-orfQ-aadA1 cassette array and sul1 gene, and the aphA1b gene
      in Tn6020 were each in segments flanked by IS26. These, together with a fourth
      IS26-flanked segment, formed a 19.5 kb genomic resistance island (GRI),
      designated AbGRI2-1, containing five copies of IS26. Part of this island was
      identical to part of the multiple antibiotic resistance region of AbaR-type
      islands found in global clone 1 (GC1). AbGRI2-1 has replaced a 40.9 kb segment
      found in the AB0057 genome. Related GRIs were identified in the same location in
      published GC2 genomes and appear to have arisen from AbGRI2-1 via IS26-mediated
      deletions. Like A91, WM99c carries ISAba1 upstream of ampC and Tn6167, an AbGRI1
      type island in the chromosomal comM gene containing sul2, tet(B), strA and strB
      genes and bla(OXA-23) in Tn2006. In WM99c, the chromosomal gene encoding OXA-Ab
      is interrupted by ISAba17. CONCLUSIONS: AbGRI2-1 is the largest so far of a new
      type of GRI designated AbGRI2 to distinguish them from the islands in comM in GC1
      isolates (AbaR type) and in GC2 isolates (AbGRI1 type).

PMID- 23169893
TI  - Opposing effects of aminocoumarins and fluoroquinolones on the SOS response and
      adaptability in Staphylococcus aureus.
AB  - OBJECTIVES: RecA is the key enzyme involved in DNA repair, recombination and
      induction of the SOS response and is central to the development of antibiotic
      resistance. Here we assessed the interaction of two different gyrase inhibitors,
      ciprofloxacin (a fluoroquinolone) and novobiocin (an aminocoumarin), on RecA
      activity and the SOS response in Staphylococcus aureus. METHODS: The influence of
      different gyrase inhibitors on the SOS response of S. aureus (including recA and
      lexA mutants) was analysed by northern blot analysis, real-time RT-PCR, western
      blot analysis and promoter activity assays. Recombination as well as mutation
      frequencies were determined for the different antibiotic combinations. RESULTS:
      We verified that ciprofloxacin leads to RecA activation and therefore induction
      of the SOS response. In contrast, novobiocin treatment resulted in an inhibition
      of recA transcription independent of LexA. When novobiocin and ciprofloxacin were
      added simultaneously, recA was reduced to the same level as with novobiocin
      alone. In combination, novobiocin also partially reduces the ciprofloxacin
      mediated induction of the LexA target gene umuC (error-prone polymerase). Apart
      from reducing recA and umuC expression, novobiocin also inhibited the frequency
      of recombination, mutation and the formation of non-haemolytic variants.
      CONCLUSION: In summary, aminocoumarins inhibit recA expression in S. aureus and
      probably delay the process of developing antibiotic resistance and gene transfer.
      A clinical re-evaluation of these compounds as well as designing more applicable
      derivatives should be considered.

PMID- 23169894
TI  - Minimal inhibitory and mutant prevention concentrations of azithromycin,
      clarithromycin and erythromycin for clinical isolates of Streptococcus
      pneumoniae.
AB  - BACKGROUND: Previous work showed a higher prevalence of macrolide/azalide
      resistance in provinces of Canada where azithromycin was the major treatment for
      Streptococcus pneumoniae as compared with regions where clarithromycin was the
      dominant treatment. These data provided a way to test the mutant selection window
      hypothesis, which predicts that the serum drug concentration (AUC(24)) relative
      to the mutant prevention concentration (MPC) would be higher for clarithromycin
      than for azithromycin. METHODS: The MIC and MPC were determined for 191
      penicillin/macrolide-susceptible clinical isolates of S. pneumoniae with
      azithromycin, clarithromycin and erythromycin using agar plate assays. RESULTS:
      The MIC(50/90) (mg/L) and MPC(50/90) (mg/L), respectively, were as follows:
      azithromycin 0.13/0.25 and 1/4; clarithromycin 0.031/0.063 and 0.13/0.5;
      erythromycin 0.063/0.13 and 0.25/2. We calculated from published pharmacokinetic
      values that the AUC(24)/MPC(90) for azithromycin was 0.85; for clarithromycin it
      was 96, and for erythromycin base and estolate it was 4 and 10, respectively.
      Thus the AUC(24)/MPC(90) was about 50 times higher for clarithromycin than for
      azithromycin. CONCLUSIONS: The elevated prevalence of azithromycin resistance may
      derive in part from a low value of AUC(24)/MPC(90) and/or time above MPC, since
      previous work indicates that the number of prescriptions per person was similar
      in the geographical regions examined.

PMID- 23169895
TI  - Efficacy of the I Can Control Asthma and Nutrition Now (ICAN) pilot program on
      health outcomes in high school students with asthma.
AB  - Asthma is the most prevalent chronic illness in childhood affecting 7 million
      youth. Many youth with asthma face another risk factor in obesity. Obesity, in
      turn, increases disorders such as asthma. Studies have recommended that asthma
      programs also address weight management in youth. Taking this into consideration,
      the I Can Control Asthma and Nutrition Now (ICAN) program is an innovative school
      based program composed of (1) nutrition and weight management education, (2)
      asthma education, and (3) monthly reenforcement visits. This pilot study tested
      the initial effectiveness of the ICAN pilot program on a variety of asthma and
      nutrition outcomes in 25 urban minority students with asthma. Over the course of
      the pilot program, significant increases in asthma knowledge, asthma self
      efficacy, asthma quality of life, asthma self-care, nutrition knowledge,
      nutrition self-efficacy, and asthma control were observed. The ICAN program has
      demonstrated promising preliminary results in improving nutrition and asthma
      health outcomes with urban minority high school students.

PMID- 23169896
TI  - Race and ethnicity data quality and imputation using U.S. Census data in an
      integrated health system: the Kaiser Permanente Southern California experience.
AB  - Research on racial and ethnic disparities using health system databases can shed
      light on the usual health care and outcomes of large numbers of individuals so
      that health inequities can be better understood and addressed. Such research
      often suffers from limitations in race/ethnicity data quality. We examined the
      quality of race/ethnicity data in a large, diverse, integrated health system that
      repeatedly collects these data on utilization of services. We tested the accuracy
      of Bayesian Improved Surname Geocoding for imputation of race/ethnicity data.
      Administrative race/ethnicity data were accurate as judged by comparison with
      self-report in adults. The Bayesian Improved Surname Geocoding method produced
      imputation results far better than chance assignment for the four most common
      race/ethnicity groups in the health system: Whites, Hispanics, Blacks, and
      Asians. These results support renewed efforts to conduct studies of racial and
      ethnic disparities in large health systems.

PMID- 23169897
TI  - Patient-centered care and outcomes: a systematic review of the literature.
AB  - Patient-centered care (PCC) has been studied for several decades. Yet a clear
      definition of PCC is lacking, as is an understanding of how specific PCC
      processes relate to patient outcomes. We conducted a systematic review of the PCC
      literature to examine the evidence for PCC and outcomes. Three databases were
      searched for all years through September 2012. We retained 40 articles for the
      analysis. Results found mixed relationships between PCC and clinical outcomes,
      that is, some studies found significant relationships between specific elements
      of PCC and outcomes but others found no relationship. There was stronger evidence
      for positive influences of PCC on satisfaction and self-management. Future
      research should examine specific dimensions of PCC and how they relate to
      technical care quality, particularly some dimensions that have not been studied
      extensively. Future research also should identify moderating and mediating
      variables in the PPC-outcomes relationship. 

PMID- 23169898
TI  - Gemcitabine-induced gouty arthritis attacks.
AB  - In this case report, we review the experience of a patient who presented with
      early stage pancreatic cancer (Stage IIb) who underwent a Whipple procedure and
      adjuvant chemoradiation. The patient's past medical history included early stage
      colon cancer in remission, post-traumatic-stress-disorder, hypertension,
      hyperlipidemia, osteoarthritis, gout, and pre-diabetes. Chemotherapy initially
      consisted of weekly gemcitabine. The patient developed acute gouty attacks after
      his second dose of gemcitabine, which brought him to the emergency room for
      emergent treatment on several occasions. Gemcitabine was held and treatment began
      with fluorouracil and concurrent radiation. After completion of his
      chemoradiation with fluorouracil, he was again treated with weekly gemcitabine
      alone. As soon as the patient started gemcitabine chemotherapy the patient
      developed gouty arthritis again, requiring discontinuation of chemotherapy. The
      patient received no additional treatment until his recent recurrence 8 months
      later where gemcitabine chemotherapy was again introduced with prophylactic
      medications consisting of allopurinol 100 mg by mouth daily and colchicine 0.6 mg
      by mouth daily throughout gemcitabine chemotherapy, and no signs of gouty
      arthritis occurred. To our knowledge, this is the first case report describing
      gout attacks associated with gemcitabine therapy. There is limited data available
      describing the mechanism that gouty arthritis may be precipitated from
      gemcitabine chemotherapy. Further monitoring and management may be required in
      patients receiving gemcitabine chemotherapy with underlying gout. 

PMID- 23169899
TI  - Hypocaloric, high-protein nutrition therapy in older vs younger critically ill
      patients with obesity.
AB  - BACKGROUND: Older patients require more protein than younger patients to achieve
      anabolism, but age-associated renal dysfunction may limit the amount of protein
      that can be safely provided. This study examined whether older, critically ill
      trauma patients with obesity can safely achieve nitrogen equilibrium and have
      positive clinical outcomes similar to younger obese patients during hypocaloric,
      high-protein nutrition therapy. METHODS: Adult patients with traumatic injury and
      obesity (body mass index [BMI] >30 kg/m(2)), admitted to the Presley Trauma
      Center from January 2009 to April 2011, were evaluated. Patients were targeted to
      receive hypocaloric, high-protein nutrition therapy (<25 kcal/kg ideal body
      weight [IBW]/d and >2 g/kg IBW/d of protein) for >10 days. Patients were
      stratified as older (>=60 years) or younger (18-59 years). RESULTS: Seventy-four
      patients (33 older, 41 younger) were studied. Older and younger patients were
      similar in BMI and injury severity. When given isonitrogenous regimens (2.3 +/-
      0.2 g/kg IBW/d), nitrogen balance was similar between older and younger patients
      (-3.2 +/- 5.7 g/d vs -4.9 +/- 9.0 g/d; P = .363). Older patients experienced a
      greater mean serum urea nitrogen concentration than younger patients (30 +/- 14
      mg/dL vs 20 +/- 9 mg/dL; P = .001) during nutrition therapy. Clinical outcomes
      were not different between groups. CONCLUSIONS: Older critically ill trauma
      patients exhibited an equivalent net protein response as younger patients during
      hypocaloric, high-protein nutrition therapy. Older patients are at greater risk
      for developing azotemia. Close monitoring is warranted.

PMID- 23169900
TI  - Response to Meyer and Gortner.

PMID- 23169901
TI  - Effect of hyperalimentation and insulin-treated hyperglycemia on tyrosine levels
      in very preterm infants receiving parenteral nutrition.
AB  - BACKGROUND: Hyperalimentation describes the increase in glucose, amino acids
      (AAs), and lipid intake designed to overcome postnatal growth failure in preterm
      infants. Preterm infants are dependent on phenylalanine metabolism to maintain
      tyrosine levels because of tyrosine concentration limits in parenteral nutrition
      (PN). We hypothesized that hyperalimentation would increase individual AA levels
      when compared with the control group but avoid high phenylalanine/tyrosine
      levels. AIM: To compare the plasma AA profiles on days 8-10 of life in preterm
      infants receiving a hyperalimentation vs a control regimen. METHODS: Infants <29
      weeks' gestation were randomized to receive hyperalimentation (30% more PN
      macronutrients) or a control regimen. Data were collected to measure
      macronutrient (including protein) intake and PN intolerance, including
      hyperglycemia, insulin use, urea, and AA profile. Plasma profiles of 23
      individual AA levels were measured on days 8-10 using ion exchange
      chromatography. RESULTS: One hundred forty-two infants were randomized with 118
      AA profiles obtained on days 8-10. There were no differences in birth weight or
      gestation between groups. There was an increase (P < .05) in 8 of 23 median
      individual plasma AA levels when comparing hyperalimentation (n = 57) with
      controls (n = 61). Only tyrosine levels (median; interquartile range) were lower
      with hyperalimentation: 27 (15-52) umol/L vs 43 (24-69) umol/L (P < .01).
      Hyperalimentation resulted in more insulin-treated hyperglycemia. No difference
      between the groups was apparent in tyrosine levels when substratified for insulin
      treated hyperglycemia. All insulin vs no insulin comparisons showed lower
      tyrosine levels with insulin treatment (P < .01). CONCLUSION: Hyperalimentation
      can result in paradoxically low plasma tyrosine levels associated with an
      increase in insulin-treated hyperglycemia.

PMID- 23169902
TI  - Force on the sacrococcygeal and ischial areas during posterior pelvic tilt in
      seated posture.
AB  - BACKGROUND: Most posture problems encountered in persons who use wheelchairs in a
      seated posture for extended periods are related to sacral sitting due to
      posterior pelvic tilt. Posterior pelvic tilt places pressure and shearing force
      on the sacrococcygeal area that can lead to pressure ulcers, but the relationship
      between pelvic tilt and force applied to the sacrococcygeal and ischial
      tuberosity areas has not yet been investigated. OBJECTIVE: To investigate the
      relationships of posterior pelvic tilt in a seated posture with vertical force
      and horizontal force on the sacrococcygeal and ischial tuberosity areas. STUDY
      DESIGN: Repeated measures design. METHODS: Thirty male and female subjects aged
      >=60 years sat in a measurement chair at varying pelvic tilt angles, and force on
      the sacrococcygeal and ischial tuberosity areas was measured. RESULTS: The
      pressure on the sacrococcygeal area increased with pelvic tilt in all subjects,
      with vertical force averaging 19% of the body weight at a pelvic tilt angle of 30
      degrees . The horizontal force on the sacrococcygeal area increased in 93% of the
      subjects, with an average increase equal to 3% of the body weight. CONCLUSIONS:
      We confirmed changes in vertical and horizontal forces on the sacrococcygeal and
      ischial tuberosity areas with a change in seated posture (pelvic tilt). CLINICAL
      RELEVANCE: We propose guidelines for rehabilitation practitioners working with
      wheelchair users to suggest improved ways of sitting in wheelchairs that avoid
      pelvic tilt angles that might promote pressure ulcers on the buttocks.

PMID- 23169912
TI  - Wildlife reservoirs of bovine tuberculosis worldwide: hosts, pathology,
      surveillance, and control.
AB  - Bovine tuberculosis due to Mycobacterium bovis is a zoonotic disease classically
      carried by cattle and spilling over into humans primarily by the ingestion of
      milk. However, in recent decades, there have been many endemic geographic
      localities where M. bovis has been detected infecting wildlife reservoirs,
      limiting the progress toward eradication of this disease from cattle. These
      include cervids in North America, badgers in Great Britain, feral pigs in Europe,
      brushtailed possums in New Zealand, and buffalo in South Africa. An overview of
      these wildlife hosts will provide insight into how these reservoirs maintain and
      spread the disease. In addition, the authors summarize the pathology, current
      ongoing methods for surveillance, and control. In many instances, it has proven
      to be more difficult to control or eradicate bovine tuberculosis in wild free
      ranging species than in domesticated cattle. Furthermore, human influences have
      often contributed to the introduction and/or maintenance of the disease in
      wildlife species. Finally, some emerging themes regarding bovine tuberculosis
      establishment in wildlife hosts, as well as conclusions regarding management
      practices to assist in bovine tuberculosis control and eradication in wildlife,
      are offered.

PMID- 23169913
TI  - In vitro characterization of influenza A virus attachment in the upper and lower
      respiratory tracts of pigs.
AB  - The binding of influenza A viruses to epithelial cells in the respiratory tract
      of mammals is a key step in the infection process. Therefore, direct assessment
      of virus-host cell interaction using virus histochemistry (VH) will enhance our
      understanding of the pathogenesis of these new viruses. For this study, the
      authors selected viruses that represented the 4 main genetic clusters of North
      American swine H1 (SwH1) viruses, along with A/California/04/2009 H1N1 and a
      vaccine strain for the positive controls, and the virus label, fluorescein
      isothiocyanate (FITC), for the negative control. A group of 5 viruses containing
      a 2-amino acid insertion adjacent to the binding site of the hemagglutinin
      protein and their presumed ancestral viruses were also examined for changes in
      binding patterns. Viruses were bound to formalin-fixed paraffin-embedded, 6-week
      old (6w) and adult pig tissues. Qualitative VH scores per respiratory zone ranged
      from + to +++, with bronchioles having the highest and most consistent scores,
      regardless of animal age. For the 6w bronchioles, a quantitative VH score was
      calculated using digital images of 5 bronchioles per tissue section using image
      analysis software. Significant differences in attachment were found among the
      SwH1 viruses (P < .0001) and among the ancestral and insertion viruses (P <
      .0001). These results provide new insights on virus binding to porcine
      respiratory epithelial cells and the usefulness of morphometric scores. The
      results also highlight limitations of in vitro techniques, including VH for
      predicting virulence and host range.

PMID- 23169914
TI  - Brain. Editorial.

PMID- 23169915
TI  - More movements in neuroimmunology.

PMID- 23169916
TI  - Towards treating spinal cord injury in 'patients': one step at a time.

PMID- 23169917
TI  - Autologous olfactory mucosal cell transplants in clinical spinal cord injury: a
      randomized double-blinded trial in a canine translational model.
AB  - This study was designed to determine whether an intervention proven effective in
      the laboratory to ameliorate the effects of experimental spinal cord injury could
      provide sufficient benefit to be of value to clinical cases. Intraspinal
      olfactory ensheathing cell transplantation improves locomotor outcome after
      spinal cord injury in 'proof of principle' experiments in rodents, suggesting the
      possibility of efficacy in human patients. However, laboratory animal spinal cord
      injury cannot accurately model the inherent heterogeneity of clinical patient
      cohorts, nor are all aspects of their spinal cord function readily amenable to
      objective evaluation. Here, we measured the effects of intraspinal
      transplantation of cells derived from olfactory mucosal cultures (containing a
      mean of ~50% olfactory ensheathing cells) in a population of spinal cord-injured
      companion dogs that accurately model many of the potential obstacles involved in
      transition from laboratory to clinic. Dogs with severe chronic thoracolumbar
      spinal cord injuries (equivalent to ASIA grade 'A' human patients at ~12 months
      after injury) were entered into a randomized double-blinded clinical trial in
      which they were allocated to receive either intraspinal autologous cells derived
      from olfactory mucosal cultures or injection of cell transport medium alone.
      Recipients of olfactory mucosal cell transplants gained significantly better fore
      hind coordination than those dogs receiving cell transport medium alone. There
      were no significant differences in outcome between treatment groups in measures
      of long tract functionality. We conclude that intraspinal olfactory mucosal cell
      transplantation improves communication across the damaged region of the injured
      spinal cord, even in chronically injured individuals. However, we find no
      evidence for concomitant improvement in long tract function.

PMID- 23169918
TI  - Back seat driving: hindlimb corticospinal neurons assume forelimb control
      following ischaemic stroke.
AB  - Whereas large injuries to the brain lead to considerable irreversible functional
      impairments, smaller strokes or traumatic lesions are often associated with good
      recovery. This recovery occurs spontaneously, and there is ample evidence from
      preclinical studies to suggest that adjacent undamaged areas (also known as peri
      infarct regions) of the cortex 'take over' control of the disrupted functions. In
      rodents, sprouting of axons and dendrites has been observed in this region
      following stroke, while reduced inhibition from horizontal or callosal
      connections, or plastic changes in subcortical connections, could also occur. The
      exact mechanisms underlying functional recovery after small- to medium-sized
      strokes remain undetermined but are of utmost importance for understanding the
      human situation and for designing effective treatments and rehabilitation
      strategies. In the present study, we selectively destroyed large parts of the
      forelimb motor and premotor cortex of adult rats with an ischaemic injury. A
      behavioural test requiring highly skilled, cortically controlled forelimb
      movements showed that some animals recovered well from this lesion whereas others
      did not. To investigate the reasons behind these differences, we used anterograde
      and retrograde tracing techniques and intracortical microstimulation. Retrograde
      tracing from the cervical spinal cord showed a correlation between the number of
      cervically projecting corticospinal neurons present in the hindlimb sensory-motor
      cortex and good behavioural recovery. Anterograde tracing from the hindlimb
      sensory-motor cortex also showed a positive correlation between the degree of
      functional recovery and the sprouting of neurons from this region into the
      cervical spinal cord. Finally, intracortical microstimulation confirmed the
      positive correlation between rewiring of the hindlimb sensory-motor cortex and
      the degree of forelimb motor recovery. In conclusion, these experiments suggest
      that following stroke to the forelimb motor cortex, cells in the hindlimb sensory
      motor area reorganize and become functionally connected to the cervical spinal
      cord. These new connections, probably in collaboration with surviving forelimb
      neurons and more complex indirect connections via the brainstem, play an
      important role for the recovery of cortically controlled behaviours like skilled
      forelimb reaching.

PMID- 23169919
TI  - The novel proteasome inhibitor BSc2118 protects against cerebral ischaemia
      through HIF1A accumulation and enhanced angioneurogenesis.
AB  - Only a minority of stroke patients receive thrombolytic therapy. Therefore, new
      therapeutic strategies focusing on neuroprotection are under review, among which,
      inhibition of the proteasome is attractive, as it affects multiple cellular
      pathways. As proteasome inhibitors like bortezomib have severe side effects, we
      applied the novel proteasome inhibitor BSc2118, which is putatively better
      tolerated, and analysed its therapeutic potential in a mouse model of cerebral
      ischaemia. Stroke was induced in male C57BL/6 mice using the intraluminal middle
      cerebral artery occlusion model. BSc2118 was intrastriatally injected 12 h post
      stroke in mice that had received normal saline or recombinant tissue-plasminogen
      activator injections during early reperfusion. Brain injury, behavioural tests,
      western blotting, MMP9 zymography and analysis of angioneurogenesis were
      performed for up to 3 months post-stroke. Single injections of BSc2118 induced
      long-term neuroprotection, reduced functional impairment, stabilized blood-brain
      barrier through decreased MMP9 activity and enhanced angioneurogenesis when given
      no later than 12 h post-stroke. On the contrary, recombinant tissue-plasminogen
      activator enhanced brain injury, which was reversed by BSc2118. Protein
      expression of the transcription factor HIF1A was significantly increased in
      saline-treated and recombinant tissue-plasminogen activator-treated mice after
      BSc2118 application. In contrast, knock-down of HIF1A using small interfering RNA
      constructs or application of the HIF1A inhibitor YC1 (now known as RNA-binding
      motif, single-stranded-interacting protein 1 (RBMS1)) reversed BSc2118-induced
      neuroprotection. Noteworthy, loss of neuroprotection after combined treatment
      with BSc2118 and YC1 in recombinant tissue-plasminogen activator-treated animals
      was in the same order as in saline-treated mice, i.e. reduction of recombinant
      tissue-plasminogen activator toxicity through BSc2118 did not solely depend on
      HIF1A. Thus, the proteasome inhibitor BSc2118 is a promising new candidate for
      stroke therapy, which may in addition alleviate recombinant tissue-plasminogen
      activator-induced brain toxicity.

PMID- 23169920
TI  - Interleukin 6-preconditioned neural stem cells reduce ischaemic injury in stroke
      mice.
AB  - Transplantation of neural stem cells provides a promising therapy for stroke. Its
      efficacy, however, might be limited because of massive grafted-cell death after
      transplantation, and its insufficient capability for tissue repair. Interleukin 6
      is a pro-inflammatory cytokine involved in the pathogenesis of various
      neurological disorders. Paradoxically, interleukin 6 promotes a pro-survival
      signalling pathway through activation of signal transducer and activator of
      transcription 3. In this study, we investigated whether cellular reprogramming of
      neural stem cells with interleukin 6 facilitates the effectiveness of cell
      transplantation therapy in ischaemic stroke. Neural stem cells harvested from the
      subventricular zone of foetal mice were preconditioned with interleukin 6 in
      vitro and transplanted into mouse brains 6 h or 7 days after transient middle
      cerebral artery occlusion. Interleukin 6 preconditioning protected the grafted
      neural stem cells from ischaemic reperfusion injury through signal transducer and
      activator of transcription 3-mediated upregulation of manganese superoxide
      dismutase, a primary mitochondrial antioxidant enzyme. In addition, interleukin 6
      preconditioning induced secretion of vascular endothelial growth factor from the
      neural stem cells through activation of signal transducer and activator of
      transcription 3, resulting in promotion of angiogenesis in the ischaemic brain.
      Furthermore, transplantation of interleukin 6-preconditioned neural stem cells
      significantly attenuated infarct size and improved neurological performance
      compared with non-preconditioned neural stem cells. This interleukin 6-induced
      amelioration of ischaemic insults was abolished by transfecting the neural stem
      cells with signal transducer and activator of transcription 3 small interfering
      RNA before transplantation. These results indicate that preconditioning with
      interleukin 6, which reprograms neural stem cells to tolerate oxidative stress
      after ischaemic reperfusion injury and to induce angiogenesis through activation
      of signal transducer and activator of transcription 3, is a simple and beneficial
      approach for enhancing the effectiveness of cell transplantation therapy in
      ischaemic stroke.

PMID- 23169922
TI  - Parkinson's disease accelerates age-related decline in haptic perception by
      altering somatosensory integration.
AB  - This study investigated how Parkinson's disease alters haptic perception and the
      underlying mechanisms of somatosensory and sensorimotor integration. Changes in
      haptic sensitivity and acuity (the abilities to detect and to discriminate
      between haptic stimuli) due to Parkinson's disease were systematically quantified
      and contrasted to the performance of healthy older and young adults. Using a
      robotic force environment, virtual contours of various curvatures were presented.
      Participants explored these contours with their hands and indicated verbally
      whether they could detect or discriminate between two contours. To understand
      what aspects of sensory or sensorimotor integration are altered by ageing and
      disease, we manipulated the sensorimotor aspect of the task: the robot either
      guided the hand along the contour or the participant actively moved the hand.
      Active exploration relies on multimodal sensory and sensorimotor integration,
      while passive guidance only requires sensory integration of proprioceptive and
      tactile information. The main findings of the study are as follows: first, a
      decline in haptic precision can already be observed in adults before the age of
      70 years. Parkinson's disease may lead to an additional decrease in haptic
      sensitivity well beyond the levels typically seen in middle-aged and older
      adults. Second, the haptic deficit in Parkinson's disease is general in nature.
      It becomes manifest as a decrease in sensitivity and acuity (i.e. a smaller
      perceivable range and a diminished ability to discriminate between two
      perceivable haptic stimuli). Third, thresholds during both active and passive
      exploration are elevated, but not significantly different from each other. That
      is, active exploration did not enhance the haptic deficit when compared to
      passive hand motion. This implies that Parkinson's disease affects early stages
      of somatosensory integration that ultimately have an impact on processes of
      sensorimotor integration. Our results suggest that the known motor problems in
      Parkinson's disease that are generally characterized as a failure of sensorimotor
      integration may, in fact, have a sensory origin.

PMID- 23169921
TI  - S100B is increased in Parkinson's disease and ablation protects against MPTP
      induced toxicity through the RAGE and TNF-alpha pathway.
AB  - Parkinson's disease is a neurodegenerative disorder that can, at least partly, be
      mimicked by the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. S100B is
      a calcium-binding protein expressed in, and secreted by, astrocytes. There is
      increasing evidence that S100B acts as a cytokine or damage-associated molecular
      pattern protein not only in inflammatory but also in neurodegenerative diseases.
      In this study, we show that S100B protein levels were higher in post-mortem
      substantia nigra of patients with Parkinson's disease compared with control
      tissue, and cerebrospinal fluid S100B levels were higher in a large cohort of
      patients with Parkinson's disease compared with controls. Correspondingly, mice
      treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine showed upregulated
      S100B messenger RNA and protein levels. In turn, ablation of S100B resulted in
      neuroprotection, reduced microgliosis and reduced expression of both the receptor
      for advanced glycation endproducts and tumour necrosis factor-alpha. Our results
      demonstrate a role of S100B in the pathophysiology of Parkinson's disease.
      Targeting S100B may emerge as a potential treatment strategy in this disorder.

PMID- 23169924
TI  - A feasibility study of the intraductal administration of chemotherapy.
AB  - Preclinical data have shown the potential of the intraductal administration of
      chemotherapy for breast cancer prevention. Direct translation of this work has
      been stymied by the anatomical differences between rodents (one duct per teat)
      and women (5-9 ductal systems per breast). The objective of this phase I study
      was to show the safety and feasibility of intraductal administration of
      chemotherapy drugs into multiple ducts within one breast in women awaiting
      mastectomy for treatment of invasive cancer. Thirty subjects were enrolled in
      this dose escalation study conducted at a single center in Beijing, China. Under
      local anesthetic, one of two chemotherapy drugs, carboplatin or pegylated
      liposomal doxorubicin (PLD), was administered into five to eight ducts at three
      dose levels. Pharmacokinetic analysis has shown that carboplatin was rapidly
      absorbed into the bloodstream, whereas PLD, though more erratic, was absorbed
      after a delay. Pathologic analysis showed marked effects on breast duct
      epithelium in ducts treated with either drug compared with untreated ducts. The
      study investigators had no difficulty in identifying or cannulating ducts except
      in one case with a central cancer with subareolar involvement. This study shows
      the safety and feasibility of intraductal administration of chemotherapy into
      multiple ducts for the purpose of breast cancer prevention. This is an important
      step toward implementation of this strategy as a "chemical mastectomy", where the
      potential for carcinogenesis in the ductal epithelium is eliminated
      pharmacologically, locally, and without the need for surgery.

PMID- 23169923
TI  - Visual cortical activity reflects faster accumulation of information from
      cortically blind fields.
AB  - Brain responses (from functional magnetic resonance imaging) and components of
      information processing were investigated in nine cortically blind observers
      performing a global direction discrimination task. Three of these subjects had
      responses in perilesional cortex in response to blind field stimulation, whereas
      the others did not. We used the EZ-diffusion model of decision making to
      understand how cortically blind subjects make a perceptual decision on stimuli
      presented within their blind field. We found that these subjects had slower
      accumulation of information in their blind fields as compared with their good
      fields and to intact controls. Within cortically blind subjects, activity in
      perilesional tissue, V3A and hMT+ was associated with a faster accumulation of
      information for deciding direction of motion of stimuli presented in the blind
      field. This result suggests that the rate of information accumulation is a
      critical factor in the degree of impairment in cortical blindness and varies
      greatly among affected individuals. Retraining paradigms that seek to restore
      visual functions might benefit from focusing on increasing the rate of
      information accumulation.

PMID- 23169926
TI  - 53-Year-old man with fever, malaise and dyspnoea.

PMID- 23169925
TI  - Antiphospholipid syndrome presenting with acute digital ischaemia, avascular
      necrosis of the femoral head and superior mesenteric artery thrombus.
AB  - This case illustrates a rare and unique case of a 73-year-old woman who presents
      with a rapidly developing digital ischaemia, superior mesenteric artery thrombus
      with positive-lupus anticoagulant. She then developed avascular necrosis of the
      femoral head. Discussion of the process of diagnosis and management of
      antiphospholipid syndrome and catastrophic antiphospholipid syndrome are
      reported.

PMID- 23169927
TI  - Celiac disease with pulmonary haemosiderosis and cardiomyopathy.
AB  - Celiac disease or pulmonary haemosiderosis can be associated with several
      distinguished conditions. Pulmonary haemosiderosis is a rare, severe and fatal
      disease characterised by recurrent episodes of alveolar haemorrhage, haemoptysis
      and anaemia. Association of pulmonary haemosiderosis and celiac disease is
      extremely rare. We describe a case of celiac disease presented with dilated
      cardiomyopathy and pulmonary haemosiderosis without gastrointestinal symptoms of
      celiac disease. In addition, vitamin A deficiency was detected. This case
      suggests that celiac disease should be considered in patients with cardiomyopathy
      and/or pulmonary haemosiderosis regardless of the intestinal symptoms of celiac
      disease.

PMID- 23169928
TI  - Truly resistant hypertension?
AB  - A young man presented with severe hypertension with evidence of both neurological
      and cardiovascular end-organ damage. Investigation revealed a small right kidney
      and a left renal artery aneurysm. Significant hypertension persisted even after
      right nephrectomy. Despite extensive investigation, no evidence was found to
      implicate the aneurysm in the causation of his high blood pressure. No
      alternative cause for hypertension was found, yet blood pressure was high even
      during hospital admission and observed medication dosing with eight
      antihypertensive agents. Sustained hypertension resulted in worsening left
      ventricular hypertrophy and he died suddenly at a tragically young age several
      years after presentation. This gentleman had truly resistant hypertension, a
      clinical problem which can be very difficult to manage.

PMID- 23169930
TI  - Structural loop between the cerebellum and the superior temporal sulcus: evidence
      from diffusion tensor imaging.
AB  - The cerebellum is believed to play an essential role in a variety of motor and
      cognitive functions through reciprocal interaction with the cerebral cortex.
      Recent findings suggest that cerebellar involvement in the network specialized
      for visual body motion processing may be mediated through interaction with the
      right superior temporal sulcus (STS). Yet, the underlying pattern of structural
      connectivity between the STS and the cerebellum remains unidentified. In the
      present work, diffusion tensor imaging analysis on seeds derived from functional
      magnetic resonance imaging during a task on point-light biological motion
      perception uncovers a structural pathway between the right posterior STS and the
      left cerebellar lobule Crus I. The findings suggest existence of a structural
      loop underpinning bidirectional communication between the STS and cerebellum.
      This connection might also be of potential value for other visual social
      abilities. 

PMID- 23169931
TI  - Development and validation of a stability-indicating RP-HPLC assay method and
      stress degradation studies on dapiprazole.
AB  - Dapiprazole (DPZ) was subjected to different stress conditions prescribed by the
      International Conference on Harmonization. A stability-indicating high
      performance liquid chromatography method was developed for the analysis of the
      drug in the presence of its degradation products. The degradation was found to
      occur in hydrolytic, and to some extent, photolytic conditions, however, the drug
      was stable to oxidative and thermal stress. The drug was particularly labile
      under neutral and alkaline hydrolytic conditions. The assay was involved an
      isocratic elution of DPZ in a Kromasil 100C18 column using a mobile phase
      composition of water (pH 6.5, 0.05%, w/v, 1-heptane sulfonic acid) and
      acetonitrile (40:60, v/v). The flow rate was 0.8 mL/min and the detection was
      conducted at 246 nm. The assay method was found to be linear from 5 to 30 ug/mL.
      The method was validated for linearity, range, precision, accuracy, specificity,
      selectivity, limit of detection and limit of quantitation. 

PMID- 23169929
TI  - Vegetarian diets and the incidence of cancer in a low-risk population.
AB  - BACKGROUND: Cancer is the second leading cause of death in the United States.
      Dietary factors account for at least 30% of all cancers in Western countries. As
      people do not consume individual foods but rather combinations of them, the
      assessment of dietary patterns may offer valuable information when determining
      associations between diet and cancer risk. METHODS: We examined the association
      between dietary patterns (non-vegetarians, lacto, pesco, vegan, and semi
      vegetarian) and the overall cancer incidence among 69,120 participants of the
      Adventist Health Study-2. Cancer cases were identified by matching to cancer
      registries. Cox proportional hazard regression analysis was conducted to estimate
      hazard ratios, with "attained age" as the time variable. RESULTS: A total of
      2,939 incident cancer cases were identified. The multivariate HR of overall
      cancer risk among vegetarians compared with non-vegetarians was statistically
      significant [HR, 0.92; 95% confidence interval (CI), 0.85-0.99] for both genders
      combined. Also, a statistically significant association was found between
      vegetarian diet and cancers of the gastrointestinal tract (HR, 0.76; 95% CI, 0.63
      0.90). When analyzing the association of specific vegetarian dietary patterns,
      vegan diets showed statistically significant protection for overall cancer
      incidence (HR, 0.84; 95% CI, 0.72-0.99) in both genders combined and for female
      specific cancers (HR, 0.66; 95% CI, 0.47-0.92). Lacto-ovo-vegetarians appeared to
      be associated with decreased risk of cancers of the gastrointestinal system (HR,
      0.75; 95% CI, 0.60-0.92). CONCLUSION: Vegetarian diets seem to confer protection
      against cancer. IMPACT: Vegan diet seems to confer lower risk for overall and
      female-specific cancer than other dietary patterns. The lacto-ovo-vegetarian
      diets seem to confer protection from cancers of the gastrointestinal tract.

PMID- 23169932
TI  - An HPLC method for the determination of nifekalant hydrochloride in canine plasma
      and its application to a pharmacokinetic study.
AB  - In this study, a simple and selective high-performance liquid chromatography
      method was developed and validated for the determination of nifekalant
      hydrochloride in canine plasma. Liquid-liquid extraction was used to separate
      nifekalant hydrochloride from canine plasma and the mean extraction recoveries of
      nifekalant hydrochloride and the internal standard were 82.31 and 94.81%,
      respectively. The chromatographic separation was performed on a Dikma Diamonsil
      column with a mobile phase consisting of acetonitrile-20mM phosphate buffer (pH
      6.2; 30:70, v/v) with flow rate of 1.0 mL/min. The standard curve was linear over
      the concentration range of 20-10,000 ng/mL (r(2) > 0.99). The intra-batch and
      inter-batch accuracy for nifekalant hydrochloride at four concentrations were
      93.14-100.47% and 96.12-103.77%, respectively. The relative standard deviations
      were less than 15%. The method was successfully applied to a pharmacokinetic
      study after the intravenous administration of nifekalant hydrochloride to beagle
      dogs. 

PMID- 23169934
TI  - The Global Enteric Multicenter Study (GEMS): impetus, rationale, and genesis.
AB  - Diarrheal disease remains one of the top 2 causes of young child mortality in the
      developing world. Whereas improvements in water/sanitation infrastructure and
      hygiene can diminish transmission of enteric pathogens, vaccines can also hasten
      the decline of diarrheal disease morbidity and mortality. From 1980 through
      approximately 2004, various case/control and small cohort studies were undertaken
      to address the etiology of pediatric diarrhea in developing countries. Many
      studies had methodological limitations and came to divergent conclusions, making
      it difficult to prioritize the relative importance of different pathogens.
      Consequently, in the first years of the millennium there was no consensus on what
      diarrheal disease vaccines should be developed or implemented; however, there was
      consensus on the need for a well-designed study to obtain information on the
      etiology and burden of more severe forms of diarrheal disease to guide global
      investment and implementation decisions. Accordingly, the Global Enteric
      Multicenter Study (GEMS) was designed to overcome drawbacks of earlier studies
      and determine the etiology and population-based burden of pediatric diarrheal
      disease. GEMS, which includes one of the largest case/control studies of an
      infectious disease syndrome ever undertaken (target approximately 12,600
      analyzable cases and 12,600 controls), was rolled out in 4 sites in sub-Saharan
      Africa (Gambia, Kenya, Mali, Mozambique) and 3 in South Asia (Bangladesh, India,
      Pakistan), with each site linked to a population under demographic surveillance
      (total approximately 467,000 child years of observation among children <5 years
      of age). GEMS data will guide investment and help prioritize strategies to
      mitigate the morbidity and mortality of pediatric diarrheal disease.

PMID- 23169935
TI  - Some epidemiologic, clinical, microbiologic, and organizational assumptions that
      influenced the design and performance of the Global Enteric Multicenter Study
      (GEMS).
AB  - The overall aim of the Global Enteric Multicenter Study-1 (GEMS-1) is to identify
      the etiologic agents associated with moderate-to-severe diarrhea (MSD) among
      children <5 years of age, and thereby the attributable pathogen-specific
      population-based incidence of MSD, to guide investments in research and public
      health interventions against diarrheal disease. To accomplish this, 9 core
      assumptions were vetted through widespread consultation: (1) a limited number of
      etiologic agents may be responsible for most MSD; (2) a definition of MSD can be
      crafted that encompasses cases that might otherwise be fatal in the community
      without treatment; (3) MSD seen at sentinel centers is a proxy for fatal
      diarrheal disease in the community; (4) matched case/control is the appropriate
      epidemiologic design; (5) methods across the sites can be standardized and
      rigorous quality control maintained; (6) a single 60-day postenrollment visit to
      case and control households creates mini-cohorts, allowing comparisons; (7) broad
      support for GEMS-1 messages can be achieved by incorporating advice from public
      health spokespersons; (8) results will facilitate the setting of investment and
      intervention priorities; and (9) wide acceptance and dissemination of the GEMS-1
      results can be achieved.

PMID- 23169937
TI  - Statistical methods in the Global Enteric Multicenter Study (GEMS).
AB  - The Global Enteric Multicenter Study (GEMS) is an investigation of the burden
      (number of cases and incidence) of moderate-to-severe diarrhea (MSD) in children
      <60 months of age at 7 sites in sub-Saharan Africa and South Asia. The population
      attributable fraction for a putative pathogen, either unadjusted or adjusted for
      other pathogens, is estimated using the proportion of MSD cases from whom the
      pathogen was isolated and the odds ratio for MSD and the pathogen from
      conditional logistic regression modeling. The adjusted attributable fraction,
      proportion of MSD cases taken to a sentinel health center (SHC), number of cases
      presenting to an SHC, and the site's population are used to estimate the annual
      number of MSD cases and MSD incidence rate attributable to a pathogen or group of
      pathogens. Associations with death and nutritional outcomes, ascertained at
      follow-up visits to case and control households, are evaluated both in MSD cases
      and in the population.

PMID- 23169938
TI  - Data management and other logistical challenges for the GEMS: the data
      coordinating center perspective.
AB  - The Cooperative Studies Program Coordinating Center provided the data management,
      administrative, and statistical support to the Global Enteric Multicenter Study
      (GEMS). The GEMS study, the largest epidemiological study in the diarrheal
      disease area among children <5 years of age, was carried out in 4 African
      countries and 3 Asian countries. Given the geographical and geopolitical
      differences among the countries, the administration of a centralized data
      management operation was a major challenge. The sheer volume of the data that
      were collected, regular transfer of the data to a centralized database, and the
      cleaning of the same also posed some challenges. This paper outlines the details
      of the support that the data coordinating center provided and the challenges
      faced during the course of the study.

PMID- 23169936
TI  - The Global Enteric Multicenter Study (GEMS) of diarrheal disease in infants and
      young children in developing countries: epidemiologic and clinical methods of the
      case/control study.
AB  - BACKGROUND: Diarrhea is a leading cause of illness and death among children aged
      <5 years in developing countries. This paper describes the clinical and
      epidemiological methods used to conduct the Global Enteric Multicenter Study
      (GEMS), a 3-year, prospective, age-stratified, case/control study to estimate the
      population-based burden, microbiologic etiology, and adverse clinical
      consequences of acute moderate-to-severe diarrhea (MSD) among a censused
      population of children aged 0-59 months seeking care at health centers in sub
      Saharan Africa and South Asia. METHODS: GEMS was conducted at 7 field sites, each
      serving a population whose demography and healthcare utilization practices for
      childhood diarrhea were documented. We aimed to enroll 220 MSD cases per year
      from selected health centers serving each site in each of 3 age strata (0-11, 12
      23, and 24-59 months), along with 1-3 matched community controls. Cases and
      controls supplied clinical, epidemiologic, and anthropometric data at enrollment
      and again approximately 60 days later, and provided enrollment stool specimens
      for identification and characterization of potential diarrheal pathogens. Verbal
      autopsy was performed if a child died. Analytic strategies will calculate the
      fraction of MSD attributable to each pathogen and the incidence, financial costs,
      nutritional consequences, and case fatality overall and by pathogen. CONCLUSIONS:
      When completed, GEMS will provide estimates of the incidence, etiology, and
      outcomes of MSD among infants and young children in sub-Saharan Africa and South
      Asia. This information can guide development and implementation of public health
      interventions to diminish morbidity and mortality from diarrheal diseases.

PMID- 23169939
TI  - Case/control studies with follow-up: Constructing the source population to
      estimate effects of risk factors on development, disease, and survival.
AB  - If individuals in a case/control study are subsequently observed as a cohort of
      cases and a cohort of controls, weighted regression analyses can be used to
      estimate the association between the exposures initially recorded and events
      occurring during the follow-up of the 2 cohorts. Such analyses can be
      conceptualized as being undertaken on a reconstructed source population from
      which cases and controls stem. To simulate this population, the cohort of cases
      is added to the cohort of controls expanded with the reciprocal of the case
      disease incidence odds (the sampling weight) to include all individuals in the
      source population who did not develop the case disease. We use a simulated
      dataset to illustrate how weighted generalized linear model regression can be
      used to estimate the association between an exposure captured during the
      case/control study component and an outcome that occurs during follow-up.

PMID- 23169941
TI  - Diagnostic microbiologic methods in the GEMS-1 case/control study.
AB  - To understand the etiology of moderate-to-severe diarrhea among children in high
      mortality areas of sub-Saharan Africa and South Asia, we performed a
      comprehensive case/control study of children aged <5 years at 7 sites. Each site
      employed an identical case/control study design and each utilized a uniform
      comprehensive set of microbiological assays to identify the likely bacterial,
      viral and protozoal etiologies. The selected assays effected a balanced
      consideration of cost, robustness and performance, and all assays were performed
      at the study sites. Identification of bacterial pathogens employed streamlined
      conventional bacteriologic biochemical and serological algorithms. Diarrheagenic
      Escherichia coli were identified by application of a multiplex polymerase chain
      reaction assay for enterotoxigenic, enteroaggregative, and enteropathogenic E.
      coli. Rotavirus, adenovirus, Entamoeba histolytica, Giardia enterica, and
      Cryptosporidium species were detected by commercially available enzyme
      immunoassays on stool samples. Samples positive for adenovirus were further
      evaluated for adenovirus serotypes 40 and 41. We developed a novel multiplex
      assay to detect norovirus (types 1 and 2), astrovirus, and sapovirus. The
      portfolio of diagnostic assays used in the GEMS study can be broadly applied in
      developing countries seeking robust cost-effective methods for enteric pathogen
      detection.

PMID- 23169940
TI  - A systematic review and meta-analysis of the association between Giardia lamblia
      and endemic pediatric diarrhea in developing countries.
AB  - We performed a systematic literature review and meta-analysis examining the
      association between diarrhea in young children in nonindustrialized settings and
      Giardia lamblia infection. Eligible were case/control and longitudinal studies
      that defined the outcome as acute or persistent (>14 days) diarrhea, adjusted for
      confounders and lasting for at least 1 year. Data on G. lamblia detection (mainly
      in stools) from diarrhea patients and controls without diarrhea were abstracted.
      Random effects model meta-analysis obtained pooled odds ratios (ORs) and 95%
      confidence intervals (CIs). Twelve nonindustrialized-setting acute pediatric
      diarrhea studies met the meta-analysis inclusion criteria. Random-effects model
      meta-analysis of combined results (9774 acute diarrhea cases and 8766 controls)
      yielded a pooled OR of 0.60 (95% CI, .38-.94; P = .03), indicating that G.
      lamblia was not associated with acute diarrhea. However, limited data suggest
      that initial Giardia infections in early infancy may be positively associated
      with diarrhea. Meta-analysis of 5 persistent diarrhea studies showed a pooled OR
      of 3.18 (95% CI, 1.50-6.76; P < .001), positively linking Giardia with that
      syndrome. The well-powered Global Enteric Multicenter Study (GEMS) is
      prospectively addressing the association between G. lamblia infection and
      diarrhea in children in developing countries.

PMID- 23169942
TI  - Factors that explain excretion of enteric pathogens by persons without diarrhea.
AB  - Excretion of enteropathogens by subjects without diarrhea influences our
      appreciation of the role of these pathogens as etiologic agents. Characteristics
      of the pathogens and host and environmental factors help explain asymptomatic
      excretion of diarrheal pathogens by persons without diarrhea. After causing acute
      diarrhea followed by clinical recovery, some enteropathogens are excreted
      asymptomatically for many weeks. Thus, in a prevalence survey of persons without
      diarrhea, some may be excreting pathogens from diarrheal episodes experienced
      many weeks earlier. Volunteer challenges with Vibrio cholerae O1, enterotoxigenic
      Escherichia coli (ETEC), enteropathogenic E. coli, Campylobacter jejuni, and
      Giardia lamblia document heterogeneity among enteropathogen strains, with some
      inexplicably not eliciting diarrhea. The immune host may not manifest diarrhea
      following ingestion of a pathogen but may nevertheless asymptomatically excrete.
      Some human genotypes render them less susceptible to symptomatic or severe
      diarrheal infection with certain pathogens such as Vibrio cholerae O1 and
      norovirus. Pathogens in stools of individuals without diarrhea may reflect recent
      ingestion of inocula too small to cause disease in otherwise susceptible hosts or
      of animal pathogens (eg, bovine or porcine ETEC) that do not cause human illness.

PMID- 23169943
TI  - Laboratory diagnostic challenges in case/control studies of diarrhea in
      developing countries.
AB  - Case/control studies of acute infectious diarrhea require accurate and dependable
      laboratory tests to detect pathogens in samples from both symptomatic patients
      and healthy control subjects. The methods used to detect these pathogens have
      usually been evaluated on patient samples only, and their performance on samples
      from control subjects is mostly unknown. Because many pathogens occur at a high
      overall frequency in developing countries and thus may be present in a notable
      proportion of control subjects as well as patients, the relative ability of a
      diagnostic test to detect these pathogens in diarrheic and normal stools can have
      a profound effect on the interpretation of case/control data.

PMID- 23169944
TI  - Exploring household economic impacts of childhood diarrheal illnesses in 3
      African settings.
AB  - Beyond the morbidity and mortality burden of childhood diarrhea in sub-Saharan
      African are significant economic costs to affected households. Using survey data
      from 3 of the 4 sites in sub-Saharan Africa (Gambia, Kenya, Mali) participating
      in the Global Enteric Multicenter Study (GEMS), we estimated the direct medical,
      direct nonmedical, and indirect (productivity losses) costs borne by households
      due to diarrhea in young children. Mean cost per episode was $2.63 in Gambia,
      $6.24 in Kenya, and $4.11 in Mali. Direct medical costs accounted for less than
      half of these costs. Mean costs understate the distribution of costs, with 10% of
      cases exceeding $6.50, $11.05, and $13.84 in Gambia, Kenya, and Mali. In all
      countries there was a trend toward lower costs among poorer households and in 2
      of the countries for diarrheal illness affecting girls. For poor children and
      girls, this may reflect reduced household investment in care, which may result in
      increased risks of mortality.

PMID- 23169945
TI  - Determinants of household costs associated with childhood diarrhea in 3 South
      Asian settings.
AB  - In addition to being a major cause of mortality in South Asia, childhood diarrhea
      creates economic burden for affected households. We used survey data from sites
      in Bangladesh, India, and Pakistan to estimate the costs borne by households due
      to childhood diarrhea, including direct medical costs, direct nonmedical costs,
      and productivity losses. Mean cost per episode was $1.82 in Bangladesh, $3.33 in
      India, and $6.47 in Pakistan. The majority of costs for households were
      associated with direct medical costs from treatment. Mean costs understate the
      distribution of costs, with 10% of cases exceeding $6.61, $8.07, and $10.11 in
      Bangladesh, India, and Pakistan, respectively. In all countries there was a trend
      toward lower costs among poorer households and in India and Pakistan there were
      lower costs for episodes among girls. For both poor children and girls this may
      reflect rationing of care, which may result in increased risks of mortality.

PMID- 23169946
TI  - Effects of postmenopausal hormone therapy on incident atrial fibrillation: the
      Women's Health Initiative randomized controlled trials.
AB  - BACKGROUND: Atrial fibrillation (AF) is less prevalent in women versus men, but
      associated with higher risks of stroke and death in women. The role hormone
      therapy plays in AF is not well understood. METHODS AND RESULTS: The Women's
      Health Initiative randomized postmenopausal women to placebo or conjugated equine
      estrogens (0.625 mg/d) plus medroxyprogesterone acetate (2.5 mg/d) if they had a
      uterus (N=16 608) or to conjugated equine estrogens only if they had prior
      hysterectomy (N=10 739). Incident AF was identified by ECG and diagnosis codes
      from Medicare claims or hospitalization records. Hazard ratios for incident AF
      were estimated using Cox proportional hazards regression. After excluding
      participants with baseline AF, there were 611 incident AF cases over a mean of
      5.6 years among 16 128 estrogen plus progestin participants, and 683 cases over a
      mean of 7.1 years among 10 251 conjugated equine estrogens alone participants.
      Incident AF was more frequent in the active groups of both trials, reaching
      statistical significance in the trial of conjugated equine estrogens alone in
      women with prior hysterectomy (hazard ratio, 1.17; CI, 1.00-1.36; P=0.045) and in
      the pooled analysis (hazard ratio, 1.12; CI, 1.00-1.24; P=0.05), but not in the
      estrogen plus progestin trial (hazard ratio, 1.07; CI, 0.91-1.25; P=0.44). These
      results were only minimally affected by adjustment for incident stroke, coronary
      heart disease, and heart failure. CONCLUSIONS: Incident AF was modestly elevated
      in hysterectomized women randomized to postmenopausal E-alone, and in the pooled
      group randomized to E-alone or estrogen plus progestin. The trend in women with
      intact uterus receiving estrogen plus progestin, considered separately, was not
      statistically significant. CLINICAL TRIAL REGISTRATION INFORMATION:
      ClinicalTrials.gov; Identifier: NCT00000611.

PMID- 23169953
TI  - Influenza in Africa: uncovering the epidemiology of a long-overlooked disease.

PMID- 23169954
TI  - Delayed 2009 pandemic influenza A virus subtype H1N1 circulation in West Africa,
      May 2009-April 2010.
AB  - To understand 2009 pandemic influenza A virus subtype H1N1 (A[H1N1]pdm09)
      circulation in West Africa, we collected influenza surveillance data from
      ministries of health and influenza laboratories in 10 countries, including
      Cameroon, from 4 May 2009 through 3 April 2010. A total of 10,203 respiratory
      specimens were tested, of which 25% were positive for influenza virus. Until the
      end of December 2009, only 14% of all detected strains were A(H1N1)pdm09, but the
      frequency increased to 89% from January through 3 April 2010. Five West African
      countries did not report their first A(H1N1)pdm09 case until 6 months after the
      emergence of the pandemic in North America, in April 2009. The time from first
      detection of A(H1N1)pdm09 in a country to the time of A(H1N1)pdm09 predominance
      varied from 0 to 37 weeks. Seven countries did not report A(H1N1)pdm09
      predominance until 2010. Introduction and transmission of A(H1N1)pdm09 were
      delayed in this region.

PMID- 23169955
TI  - Virological surveillance of influenza-like illness among children in Ghana, 2008
      2010.
AB  - BACKGROUND: The global annual attack rate for influenza is estimated to be 10%
      20% in children, although limited information exists for Africa. In 2007, Ghana
      initiated influenza surveillance by routine monitoring of acute respiratory
      illness to obtain data on circulating strains. We describe influenza surveillance
      in children <11 years old who had influenza-like illness (ILI) from January 2008
      to December 2010. METHODS: Oropharyngeal swabs from pediatric outpatients with
      ILI attending any of 22 health facilities across the country were submitted. We
      tested swabs for influenza virus using molecular assays, virus isolation, and
      hemagglutination assays. RESULTS: Of the 2810 swabs, 636 (23%) were positive for
      influenza virus. The percentage of positives by gender was similar. The
      proportion of ILI cases positive for influenza increased with age from 11%
      (31/275) in infants (aged 0-1 years) to 31% (377/1219) among children aged 5-10
      years (P < .001). The majority of cases were influenza A (90%), of which 60% were
      influenza A(H1N1)pdm09. In all 3 years, influenza activity appeared slightly
      higher during May through July. CONCLUSIONS: During the 3 years of influenza
      surveillance in Ghana, children aged <11 years bore a high burden of influenza
      associated ILI.

PMID- 23169956
TI  - Vulnerable groups within a vulnerable population: awareness of the A(H1N1)pdm09
      pandemic and willingness to be vaccinated among pregnant women in Ivory Coast.
AB  - BACKGROUND: Because little is known about attitudes toward influenza and
      influenza vaccine among pregnant women in West Africa, before local distribution
      of A(H1N1)pdm09 vaccine in Ivory Coast we assessed knowledge of the pandemic and
      acceptance of the A(H1N1)pdm09 vaccine in a diverse population of pregnant women.
      METHODS: A cross-sectional intercept survey of 411 pregnant women in 4 prenatal
      care settings was conducted during 15-28 February 2010 in Abidjan, Ivory Coast.
      RESULTS: The majority (64.5%) of pregnant women said they had heard of the
      influenza pandemic, and of these, the majority (61.3%) were aware of the
      A(H1N1)pdm09 vaccine. However, awareness varied significantly by clinical
      setting, education level, and access to media (P < .001 for all comparisons).
      After adjustment for other sociodemographic factors, college-educated women were
      16.8 (95% confidence interval [CI], 3.3-85.2) times as likely as women without
      formal education to be aware of the pandemic. After controlling for both
      education and demographic characteristics, women with televisions were 5 times as
      likely as women without television to be aware of the pandemic (adjusted odds
      ratio [aOR], 4.94; 95% CI, 1.34-18.17). Of those aware of the influenza pandemic,
      69.8% said they would accept the A(H1N1)pdm09 vaccine while they were pregnant.
      Although awareness was highest in private prenatal care clinics, compared with
      public outpatient clinics (90.6% vs 37.5%), acceptance of vaccine was
      significantly lower in private settings, compared with public outpatient settings
      (57.3% vs 87.2%; P < .001 for each comparison). CONCLUSIONS: Gaps in knowledge
      about the influenza pandemic and vaccine highlight the challenges of pandemic
      preparedness in poorer countries, where substantial disparities in education and
      media access are evident.

PMID- 23169957
TI  - Influenza viruses in Nigeria, 2009-2010: results from the first 17 months of a
      national influenza sentinel surveillance system.
AB  - BACKGROUND: Influenza surveillance data from tropical, sub-Saharan African
      countries are limited. To better understand the epidemiology of influenza,
      Nigeria initiated influenza surveillance in 2008. METHODS: Outpatients with
      influenza-like illness (ILI) and inpatients with severe acute respiratory illness
      (SARI) were enrolled at 4 sentinel facilities. Epidemiologic data were obtained,
      and respiratory specimens were tested for influenza viruses, using real-time
      reverse-transcription polymerase chain reaction assays. RESULTS: During April
      2009-August 2010, 2841 patients were enrolled. Of 2803 specimens tested, 217
      (7.7%) were positive for influenza viruses (167 [8%] were from subjects with ILI,
      17 [5%] were from subjects with SARI, and 33 were from subjects with an
      unclassified condition). During the prepandemic period, subtype H3N2 (A[H3N2])
      was the dominant circulating influenza A virus subtype; 2009 pandemic influenza A
      virus subtype H1N1 (A[H1N1]pdm09) replaced A(H3N2) as the dominant circulating
      virus during November 2009. Among persons with ILI, A(H1N1)pdm09 was most
      frequently found in children aged 5-17 years, whereas among subjects with SARI,
      it was most frequently found in persons aged >= 65 years. The percentage of
      specimens that tested positive for influenza viruses peaked at 18.9% in February
      2010, and the majority were A(H1N1)pdm09. CONCLUSIONS: Influenza viruses cause
      ILI and SARI in Nigeria. Data from additional years are needed to better
      understand the epidemiology and seasonality of influenza viruses in Nigeria.

PMID- 23169958
TI  - Sentinel surveillance for influenza in Senegal, 1996-2009.
AB  - BACKGROUND: Data on influenza in tropical and resource-limited countries are
      scarce. In this study we present results from 14 years of influenza surveillance
      in Senegal, one of the few tropical countries in Africa from which longitudinal
      data are available. METHODS: From 1996 to 2009, we collected respiratory
      specimens from outpatients presenting with influenza-like illness at 13
      facilities in order to investigate the epidemiology of seasonal influenza and the
      characteristics of the circulating influenza viruses. Specimens were tested for
      influenza using viral isolation and/or reverse-transcription polymerase chain
      reaction (RT-PCR). RESULTS: From 1996 to 2009, specimens were obtained from 9176
      patients; 1233 (13%) were influenza-positive by virus isolation and/or RT-PCR.
      Among positive samples, 958 (77%) were influenza A, 268 (22%) influenza B, and 7
      (1%) influenza type C; of influenza A viruses, 619 (65%) were A(H3) and 339 (35%)
      A(H1), of which 13 (1%) were identified as H1N2. The proportion positive was
      similar for children <15 years, young adults 16-35 years, and adults 36-55 years
      (15%), but lower for persons >55 years (9%). Although influenza A(H1), A(H3), and
      B all circulated during most years, influenza A(H3N2) predominated during 9 of
      the 14 years. Influenza activity consistently peaked during the rainy season
      (July-September). Phylogenetic analysis showed that viruses circulating in
      Senegal were similar to contemporary viruses circulating elsewhere in the world.
      CONCLUSIONS: Our data confirm that influenza is prevalent in Senegal, occurs in
      seasonal epidemics, and contributes to the burden of respiratory diseases in all
      age groups.

PMID- 23169959
TI  - Characteristics of patients with influenza-like illness, severe acture
      respiratory illness, and laboratory-confirmed influenza at a major children's
      hospital in Angola, 2009-2011.
AB  - There are no published data on influenza trends in Angola, where pneumonia is a
      leading cause of death among young children. This study aims to describe the
      seasonal trends, types, and subtypes of influenza virus recovered from patients
      with respiratory illness who were admitted to the major children's hospital in
      Angola from May 2009 through April 2011. Nasal and oral swabs were collected from
      patients seen in the outpatient clinic with influenza-like illness (ILI) or
      hospitalized with severe acute respiratory illness (SARI) and tested for
      influenza virus by polymerase chain reaction assays. Of 691 samples collected,
      334 (48%) were from case patients with ILI, and 357 (52%) were from case patients
      with SARI. Most (86%) of these children were <5 years of age. Thirty-nine samples
      (47% SARI, 53% outpatient) tested positive for influenza virus, including 2009
      pandemic influenza A virus subtype H1N1 (A[H1N1]pdm09; n = 9), influenza A virus
      subtype H3, likely H3N2 (n = 12), and influenza B virus (n = 18). The proportion
      of specimens positive for influenza virus was 5% for ILI cases and 6% for SARI
      cases. After the peak of A(H1N1)pdm09 infection from May through September of
      2009, additional peaks of ILI and SARI were seen, especially during February
      April 2010. Influenza virus causes a small but preventable number of pneumonia
      cases among children in Angola.

PMID- 23169960
TI  - Influenza surveillance in 15 countries in Africa, 2006-2010.
AB  - BACKGROUND: In response to the potential threat of an influenza pandemic, several
      international institutions and governments, in partnership with African
      countries, invested in the development of epidemiologic and laboratory influenza
      surveillance capacity in Africa and the African Network of Influenza Surveillance
      and Epidemiology (ANISE) was formed. METHODS: We used a standardized form to
      collect information on influenza surveillance system characteristics, the number
      and percent of influenza-positive patients with influenza-like illness (ILI), or
      severe acute respiratory infection (SARI) and virologic data from countries
      participating in ANISE. RESULTS: Between 2006 and 2010, the number of ILI and
      SARI sites in 15 African countries increased from 21 to 127 and from 2 to 98,
      respectively. Children 0-4 years accounted for 48% of all ILI and SARI cases of
      which 22% and 10%, respectively, were positive for influenza. Influenza peaks
      were generally discernible in North and South Africa. Substantial cocirculation
      of influenza A and B occurred most years. CONCLUSIONS: Influenza is a major cause
      of respiratory illness in Africa, especially in children. Further strengthening
      influenza surveillance, along with conducting special studies on influenza
      burden, cost of illness, and role of other respiratory pathogens will help detect
      novel influenza viruses and inform and develop targeted influenza prevention
      policy decisions in the region.

PMID- 23169961
TI  - Epidemiological and virological characterization of 2009 pandemic influenza A
      virus subtype H1N1 in Madagascar.
AB  - BACKGROUND: Madagascar was one of the first African countries to be affected by
      the 2009 pandemic of influenza A virus subtype H1N1 [A(H1N1)pdm2009] infection.
      The outbreak started in the capital city, Antananarivo, and then spread
      throughout the country from October 2009 through February 2010. METHODS:
      Specimens from patients presenting with influenza-like illness were collected and
      shipped to the National Influenza Center in Madagascar for analyses, together
      with forms containing patient demographic and clinical information. RESULTS: Of
      the 2303 specimens tested, 1016 (44.1%) and 131 (5.7%) yielded A(H1N1)pdm09 and
      seasonal influenza virus, respectively. Most specimens (42.0%) received were
      collected from patients <10 years old. Patients <20 years old were more likely
      than patients >50 years old to be infected with A(H1N1)pdm09 (odds ratio, 2.1;
      95% confidence interval, 1.7-2.6; P < .01). Although phylogenetic analyses of
      A(H1N1)pdm09 suggested multiple introductions of the virus into Madagascar, no
      antigenic differences between A(H1N1)pdm09 viruses recovered in Madagascar and
      those that circulated worldwide were observed. CONCLUSIONS: The high proportion
      of respiratory specimens positive for A(H1N1)pdm09 is consistent with a
      widespread transmission of the pandemic in Madagascar. The age distribution of
      cases of A(H1N1)pdm09 infection suggests that children and young adults could be
      targeted for interventions that aim to reduce transmission during an influenza
      pandemic.

PMID- 23169962
TI  - Introduction of 2009 pandemic influenza A virus subtype H1N1 into South Africa:
      clinical presentation, epidemiology, and transmissibility of the first 100 cases.
AB  - BACKGROUND: We documented the introduction of 2009 pandemic influenza A virus
      subtype H1N1 (A[H1N1]pdm09) into South Africa and describe its clinical
      presentation, epidemiology, and transmissibility. METHODS: We conducted a
      prospective descriptive study of the first 100 laboratory-confirmed cases of
      A(H1N1)pdm09 infections identified through active case finding and surveillance.
      Infected patients and the attending clinicians were interviewed, and close
      contacts were followed up to investigate household transmission. FINDINGS: The
      first case was confirmed on 14 June 2009, and by 15 July 2009, 100 cases were
      diagnosed. Forty-two percent of patients reported international travel within 7
      days prior to onset of illness. Patients ranged in age from 4 to 70 years (median
      age, 21.5 years). Seventeen percent of household contacts developed influenza
      like illness, and 10% of household contacts had laboratory-confirmed A(H1N1)pdm09
      infection. We found a mean serial interval (+/- SD) of 2.3 +/- 1.3 days (range, 1
      5 days) between successive laboratory-confirmed cases in the transmission chain.
      CONCLUSIONS: A(H1N1)pdm09 established itself rapidly in South Africa.
      Transmissibility of the virus was comparable to observations from outside of
      Africa and to seasonal influenza virus strains.

PMID- 23169963
TI  - Twenty-five years of outpatient influenza surveillance in South Africa, 1984
      2008.
AB  - INTRODUCTION: Understanding the seasonality of influenza can help inform
      prevention and clinical treatment strategies. The aim of this manuscript is to
      describe the trends and epidemiology of outpatient influenza in South Africa
      prior to the influenza A(H1N1) pandemic. METHODS: Throughout each year,
      participating healthcare practitioners sent throat swabs from patients with
      influenza-like illness (ILI) to the National Institute for Communicable Diseases
      for influenza testing by immunofluorescence and viral culture through the Viral
      Watch influenza surveillance program. RESULTS: From 1984 to 2004, participating
      sites were restricted to 1 province and the annual number of specimens ranged
      from 91 to 534. In 2005 the program was expanded. By 2008 the program included
      all 9 provinces; 1276 specimens were submitted that year. The mean week of onset
      was the first week of June and the mean peak was the first week of July. The
      duration of the season ranged from 6 to 18 weeks with a mean of 10 weeks. The
      mean annual influenza detection rate was 28% (range, 23%-41%). Influenza A(H3N2)
      predominated in 14 (56%) of the 25 years, seasonal influenza A(H1N1) in 7 (28%),
      and influenza B in 2 (8%), and in 2 years multiple types cocirculated.
      CONCLUSIONS: The program has provided valuable data on the timing of the
      influenza season each year that can be useful to direct the timing of vaccination
      and assist clinicians in deciding whether to prescribe empirical antiviral
      therapy.

PMID- 23169964
TI  - Respiratory viral coinfections identified by a 10-plex real-time reverse
      transcription polymerase chain reaction assay in patients hospitalized with
      severe acute respiratory illness--South Africa, 2009-2010.
AB  - BACKGROUND: Data about respiratory coinfections with 2009 pandemic influenza A
      virus subtype H1N1 during the 2009-2010 influenza pandemic in Africa are limited.
      We used an existing surveillance program for severe acute respiratory illness to
      evaluate a new multiplex real-time polymerase chain reaction assay and
      investigate the role of influenza virus and other respiratory viruses in
      pneumonia hospitalizations during and after the influenza pandemic in South
      Africa. METHODS: The multiplex assay was developed to detect 10 respiratory
      viruses, including influenza A and B viruses, parainfluenza virus types 1-3,
      respiratory syncytial virus (RSV), enterovirus, human metapneumovirus (hMPV),
      adenovirus (AdV), and rhinovirus (RV), followed by influenza virus subtyping.
      Nasopharyngeal and oropharyngeal specimens were collected from patients
      hospitalized with pneumonia at 6 hospitals during 2009-2010. RESULTS: Validation
      against external quality controls confirmed the high sensitivity (91%) and
      specificity (100%) and user-friendliness, compared with other PCR technologies.
      Of 8173 patients, 40% had single-virus infections, 17% had coinfections, and 43%
      remained negative. The most common viruses were RV (25%), RSV (14%), AdV (13%),
      and influenza A virus (5%). Influenza virus, RSV, PIV type 3, and hMPV showed
      seasonal patterns. CONCLUSION: The data provide a better understanding of the
      viral etiology of hospitalized cases of pneumonia and demonstrate the usefulness
      of this multiplex assay in respiratory disease surveillance in South Africa.

PMID- 23169966
TI  - Influenza surveillance in Zambia, 2008-2009.
AB  - BACKGROUND: Limited information exists about influenza viruses in Africa. We used
      data from a new sentinel surveillance system to investigate the seasonality and
      characteristics of influenza, including pandemic (pdm) influenza A H1N1, in
      Zambia. METHODS: In June 2008, we established sentinel surveillance for influenza
      like illness (ILI) and severe acute respiratory illness (SARI) at 4 healthcare
      facilities in Zambia. Nasopharyngeal and oropharyngeal swabs and structured
      questionnaires were collected from eligible patients and samples were tested by
      real-time reverse-transcription polymerase chain reaction for influenza virus
      types and subtypes. RESULTS: From June 2008 to December 2009, we collected 1234
      specimens, of which 334 (27%) were ILI, and 900 (63%) were SARI. Overall, 4% (57)
      of specimens were positive for influenza. The influenza detection rate in ILI and
      SARI cases was 5% (17/334) and 4% (40/900), respectively. Among all influenza
      cases, 54 (95%) were influenza A and 3 (5%) were influenza B. Of the influenza A
      viruses, 16 (30%) were A(H1N1)pdm09, 29 (54%) were seasonal A(H1N1), 6 (11%) were
      A(H3N2), and 4 (7%) were unsubtyped. The detection rate for A(H1N1)pdm09 cases
      was highest in persons aged 5-24 years (5/98; 5%), 25-44 years (4/78; 5%), and 45
      64 years (1/17; 6%). Conversely, for seasonal influenza the detection rate was
      highest in children aged 1-4 years (18/294; 6%). Influenza virus circulation
      peaked during June-August in both years and A(H1N1)pdm09 occurred at the end of
      the influenza season in 2009. CONCLUSIONS: Seasonal influenza virus infection was
      found to be associated with both mild and severe respiratory illness in Zambia.
      Future years of surveillance are necessary to better define the seasonality and
      epidemiology of influenza in the country.

PMID- 23169965
TI  - Evolutionary dynamics of 2009 pandemic influenza A virus subtype H1N1 in South
      Africa during 2009-2010.
AB  - BACKGROUND: The 2009 pandemic influenza A virus subtype H1N1 (A[H1N1]pdm09) was
      first detected in June 2009 in South Africa and later resulted in extensive
      transmission throughout Africa. Established routine surveillance programs and
      collaboration between private and public sector laboratories allowed for
      comprehensive molecular epidemiological and antigenic investigation of the first
      and second waves of 2009-2010 pandemic influenza in South Africa. METHODS: We
      used reverse-transcription polymerase chain reaction to screen for influenza
      virus in 9792 specimens recovered during 2009 and 6915 specimens recovered during
      2010 from inpatients and outpatients with influenza-like illness or severe acute
      respiratory illness symptoms identified by surveillance programs. Influenza
      positive specimens were subjected to genetic and antigenic characterization.
      Bayesian and maximum likelihood analyses of the hemagglutinin genes of 96
      A(H1N1)pdm09 strains were used for molecular epidemiological investigations.
      Hemagglutination inhibition assays and sequencing of the PB2 and neuraminidase
      genes were used to investigate pathogenicity and resistance mutations. RESULTS:
      The A(H1N1)pdm09 epidemic occurred as a second epidemic peak following seasonal
      influenza A virus subtype H3N2 cases in 2009 and in 2010. Progressive drift away
      from the A/California/7/2009 vaccine strain was observed at both the nucleotide
      and amino acid level, with 2010 strains clustering separate to 2009 strains. A
      few unique clusters of amino acid changes in severe cases were identified, but
      most strains were antigenically similar to the vaccine strain, and no resistance
      or known pathogenicity mutations were detected. CONCLUSION: Despite limited drift
      observed over the 2 seasons in South Africa, circulating A(H1N1)pdm09 strains
      remained antigenically similar to strains identified in other northern and
      southern hemisphere countries from 2010 and 2011.

PMID- 23169967
TI  - 2009 Pandemic influenza A virus subtype H1N1 vaccination in Africa--successes and
      challenges.
AB  - To provide vaccination against infection due to 2009 pandemic influenza A virus
      subtype H1N1 (A[H1N1]pdm09) to resource-constrained countries with otherwise very
      little access to the A(H1N1)pdm09 vaccine, the World Health Organization (WHO)
      coordinated distribution of donated vaccine to selected countries worldwide,
      including those in Africa. From February through November 2010, 32.2 million
      doses were delivered to 34 countries in Africa. Of the 19.2 million doses
      delivered to countries that reported their vaccination activities to WHO, 12.2
      million doses (64%) were administered. Population coverage in these countries
      varied from 0.4% to 11%, with a median coverage of 4%. All countries targeted
      pregnant women (median proportion of all vaccine doses administered [mpv], 21%
      [range, 4%-72%]) and healthcare workers (mpv, 9% [range, 1%-73%]). Fourteen of 19
      countries targeted persons with chronic conditions (mpv, 26% [range, 5%-66%]) and
      10 of 19 countries vaccinated children (mpv, 54% [range, 17%-75%]). Most vaccine
      was distributed after peak A(H1N1)pdm09 transmission in the region. The frequency
      and severity of adverse events were consistent with those recorded after other
      inactivated influenza vaccines. Pandemic preparedness plans will need to include
      strategies to ensure more-rapid procedures to identify vaccine supplies and
      distribute and import vaccines to countries that may bear the brunt of a future
      pandemic.

PMID- 23169968
TI  - Viral etiology of influenza-like illnesses in Cameroon, January-December 2009.
AB  - BACKGROUND: No information is available on the viral etiology of upper
      respiratory tract infections in Cameroon. METHODS: We prospectively enrolled
      outpatients with influenza-like illness (ILI) presenting at 14 sentinel clinics
      located across the country from January through December 2009. The specimens were
      tested using real-time and multiplex reverse-transcription polymerase chain
      reaction methods for the detection of 15 RNA respiratory viruses. RESULTS: We
      detected at least 1 respiratory virus in 365 of 561 specimens (65.1%). Overall,
      influenza virus was the most commonly detected virus (28.2% of specimens),
      followed by human rhinovirus (17.8%); parainfluenza virus (PIV) types 1-4 (7.5%);
      enterovirus (5.9%); respiratory syncytial virus (RSV; 5.7%); human coronavirus
      (HCoV) OC43, 229E, NL63, and HKU1 (5.3%); and human metapneumovirus (HMPV; 5.0%).
      RSV (26 of 31 specimens [83.9%]), PIV (30 of 39 [76.9%]), and HRV (64 of 99
      [64.6%]) were most common among children <5 years of age. Coinfections were found
      in 53 of 365 positive specimens (14.5%), and most (71.7%) were in children <5
      years of age. While influenza virus, enterovirus, RSV, and HMPV had a defined
      period of circulation, the other viruses were detected throughout the year.
      CONCLUSIONS: We found that respiratory viruses play an important role in the
      etiology of ILI in Cameroon, particularly in children <5 years of age.

PMID- 23169969
TI  - Sentinel surveillance for influenza-like illness, severe acute respiratory
      illness, and laboratory-confirmed influenza in Kinshasa, Democratic Republic of
      Congo, 2009-2011.
AB  - Little is known about influenza in central Africa. We conducted sentinel
      surveillance for influenza-like illness, severe acute respiratory illness, and
      laboratory-confirmed influenza at 5 sites in Kinshasa, Democratic Republic of
      Congo, from January 2009 through April 2011. We obtained samples from 4156
      patients, of whom 605 (15%) had specimens containing laboratory-confirmed
      influenza virus. Apart from the period of pandemic influenza due to influenza A
      virus subtype H1N1, which occurred during August-December 2009, influenza
      activity peaked at least once each year from January through March, predominantly
      among children. These data can guide interventions to reduce the burden of
      influenza in the Democratic Republic of Congo and central Africa.

PMID- 23169970
TI  - Challenges of establishing routine influenza sentinel surveillance in Ethiopia,
      2008-2010.
AB  - Ethiopia launched influenza surveillance in November 2008. By October 2010, 176
      patients evaluated at 5 sentinel health facilities in Addis Ababa met case
      definitions for influenza-like illness or severe acute respiratory illness
      (SARI). Most patients (131 [74%]) were children aged 0-4 years. Twelve patients
      (7%) were positive for influenza virus. Most patients (109 [93%]) were aged <5
      years, of whom only 3 (2.8%) had laboratory-confirmed influenza. Low awareness of
      influenza by healthcare workers, misperceptions regarding case definitions, and
      insufficient human resources at sites could have potentially led to many missed
      cases, resulting in suboptimal surveillance.

PMID- 23169972
TI  - Spatiotemporal circulation of influenza viruses in 5 African countries during
      2008-2009: a collaborative study of the Institut Pasteur International Network.
AB  - BACKGROUND: Although recent work has described the spatiotemporal diffusion of
      influenza viruses worldwide, comprehensive data on spatiotemporal patterns of
      influenza from the African continent and Madagascar are still lacking. METHODS:
      National Influenza Centers from 5 countries-Cameroon, Cote d'Ivoire, Madagascar,
      Niger, and Senegal--collected specimens from patients presenting with influenza
      like illness who visited sentinel surveillance clinics during a 2-year period
      (2008-2009). Isolates were genetically and antigenically characterized. RESULTS:
      Overall, 8312 specimens were tested. Seasonal influenza A virus subtypes H1N1 and
      H3N2 and influenza B viruses were detected in 329, 689, and 148 specimens,
      respectively. In 2009, pandemic influenza A virus subtype H1N1 was detected in
      Madagascar most commonly (98.5% of cases). Influenza activity was either
      significant year-round or occurred during a specific period of the year in the
      African countries we evaluated. CONCLUSIONS: Our results demonstrate that, from
      Madagascar to Senegal, the epidemiologic and virologic characteristics of
      influenza viruses are diverse in terms of spatiotemporal circulation of the
      different virus types, subtypes, and strains. Our data highlight the importance
      of country-specific surveillance and of data and virus sharing, and they provide
      a rational basis to aid policy makers to develop strategies, such as vaccination
      at the right moment and with the right formulation, aimed at reducing the disease
      burden in Africa and Madagascar.

PMID- 23169973
TI  - Epidemiology, seasonality, and burden of influenza and influenza-like illness in
      urban and rural Kenya, 2007-2010.
AB  - BACKGROUND: The epidemiology and burden of influenza remain poorly defined in sub
      Saharan Africa. Since 2005, the Kenya Medical Research Institute and Centers for
      Disease Control and Prevention-Kenya have conducted population-based infectious
      disease surveillance in Kibera, an urban informal settlement in Nairobi, and in
      Lwak, a rural community in western Kenya. METHODS: Nasopharyngeal and
      oropharyngeal swab specimens were obtained from patients who attended the study
      clinic and had acute lower respiratory tract (LRT) illness. Specimens were tested
      for influenza virus by real-time reverse-transcription polymerase chain reaction.
      We adjusted the incidence of influenza-associated acute LRT illness to account
      for patients with acute LRT illness who attended the clinic but were not sampled.
      RESULTS: From March 2007 through February 2010, 4140 cases of acute LRT illness
      were evaluated in Kibera, and specimens were collected from 1197 (27%); 319 (27%)
      were positive for influenza virus. In Lwak, there were 6733 cases of acute LRT
      illness, and specimens were collected from 1641 (24%); 359 (22%) were positive
      for influenza virus. The crude and adjusted rates of medically attended influenza
      associated acute LRT illness were 6.9 and 13.6 cases per 1000 person-years,
      respectively, in Kibera, and 5.6 and 23.0 cases per 1000 person-years,
      respectively, in Lwak. In both sites, rates of influenza-associated acute LRT
      illness were highest among children <2 years old and lowest among adults >=50
      years old. CONCLUSION: In Kenya, the incidence of influenza-associated acute LRT
      illness was high in both rural and urban settings, particularly among the most
      vulnerable age groups.

PMID- 23169974
TI  - Influenza surveillance among children with pneumonia admitted to a district
      hospital in coastal Kenya, 2007-2010.
AB  - BACKGROUND: Influenza data gaps in sub-Saharan Africa include incidence, case
      fatality, seasonal patterns, and associations with prevalent disorders. METHODS:
      Nasopharyngeal samples from children aged <12 years who were admitted to Kilifi
      District Hospital during 2007-2010 with severe or very severe pneumonia and
      resided in the local demographic surveillance system were screened for influenza
      A, B, and C viruses by molecular methods. Outpatient children provided
      comparative data. RESULTS: Of 2002 admissions, influenza A virus infection was
      diagnosed in 3.5% (71), influenza B virus infection, in 0.9% (19); and influenza
      C virus infection, in 0.8% (11 of 1404 tested). Four patients with influenza
      died. Among outpatients, 13 of 331 (3.9%) with acute respiratory infection and 1
      of 196 without acute respiratory infection were influenza positive. The annual
      incidence of severe or very severe pneumonia, of influenza (any type), and of
      influenza A, was 1321, 60, and 43 cases per 100,000 <5 years of age,
      respectively. Peak occurrence was in quarters 3-4 each year, and approximately
      50% of cases involved infants: temporal association with bacteremia was absent.
      Hypoxia was more frequent among pneumonia cases involving influenza (odds ratio,
      1.78; 95% confidence interval, 1.04-1.96). Influenza A virus subtypes were
      seasonal H3N2 (57%), seasonal H1N1 (12%), and 2009 pandemic H1N1 (7%).
      CONCLUSIONS: The burden of influenza was small during 2007-2010 in this pediatric
      hospital in Kenya. Influenza A virus subtype H3N2 predominated, and 2009 pandemic
      influenza A virus subtype H1N1 had little impact.

PMID- 23169975
TI  - Epidemiology of 2009 pandemic influenza A virus subtype H1N1 among Kenyans aged 2
      months to 18 years, 2009-2010.
AB  - BACKGROUND: The US Army Medical Research Unit-Kenya (USAMRU-K) conducts
      surveillance for influenza-like illness (ILI) in Kenya. We describe the temporal
      and geographic progression of A(H1N1)pdm09 as it emerged in Kenya and
      characterize the outpatient population with A(H1N1)pdm09 infection. METHODS: We
      included patients with ILI aged 2 months to 18 years enrolled during June 2009
      August 2010. Respiratory specimens were tested by real-time reverse-transcription
      polymerase chain reaction for influenza virus. Patients with A(H1N1)pdm09
      infection were compared to those with seasonal influenza A virus infection and
      those with ILI who had no virus or a virus other than influenza virus identified
      (hereafter, "noninfluenza ILI"). RESULTS: Of 4251 patients with ILI, 193 had
      laboratory-confirmed A(H1N1)pdm09 infection. The first pandemic influenza case
      detected by USAMRU-K surveillance was in August 2009; peak activity nationwide
      occurred during October-November 2009. Patients with A(H1N1)pdm09 infection were
      more likely to be school-aged, compared with patients with seasonal influenza A
      virus infection (prevalence ratio [PR], 2.0; 95% confidence interval [CI], 1.3
      3.1) or noninfluenza ILI (PR, 3.2; 95% CI, 2.4-4.3). CONCLUSIONS: USAMRU-K ILI
      surveillance detected the geographic and temporal distribution of pandemic
      influenza in Kenya. The age distribution of A(H1N1)pdm09 infections included more
      school-aged children, compared with seasonal influenza A virus infection and
      noninfluenza ILI.

PMID- 23169977
TI  - Results from the first 30 months of national sentinel surveillance for influenza
      in Tanzania, 2008-2010.
AB  - Limited data exist on the burden of influenza in developing countries. In 2008,
      in order to better understand the epidemiology of influenza virus infection in
      Tanzania, the Tanzanian Ministry of Health and Social Welfare created a sentinel
      surveillance system for influenza. At 5 hospitals across the country, patients
      with influenza-like illness (ILI) and severe acute respiratory illness (SARI) had
      oropharyngeal and nasopharyngeal samples collected. At the National Influenza
      Center in Dar es Salaam, specimens were tested for influenza using real-time
      polymerase chain reaction tests. From May 2008 through November 2010, a total of
      1794 samples were collected from 5 sentinel sites, of which 61% were from
      patients with ILI and 39% were from patients with SARI. Of all ILI and SARI
      samples, 8.0% were positive for influenza; 6.9% yielded influenza A virus, and
      1.1% yielded influenza B virus. Most influenza A virus was subtype H3, which
      circulated in nearly every month of 2010. The proportion of influenza-positive
      cases was similar among ILI (8.5%) and SARI (7.3%) patients (P = .39). In
      multivariate logistic regression, influenza-positive SARI cases were more likely
      than influenza-negative SARI cases to have had rhonchi (adjusted OR [aOR], 2.31;
      95% confidence interval [CI], 1.14-4.67), nasal discharge (aOR, 4.57; 95% CI,
      1.30-16.10), and stridor (aOR, 2.63; 95% CI, 1.17-5.90). Influenza-positive ILI
      patients had a longer duration of fever on presentation, compared with influenza
      negative ILI patients (median, 4 vs 3 days; P = .004). Otherwise, there was no
      difference in signs or symptoms among influenza-positive and influenza-negative
      ILI patients. During 2.5 years of surveillance for influenza at 5 geographically
      disbursed sites in Tanzania, we found that influenza circulated year-round.
      Surveillance should continue in order to fully understand the seasonality and
      epidemiology of influenza in Tanzania.

PMID- 23169976
TI  - Influenza sentinel surveillance in Rwanda, 2008-2010.
AB  - BACKGROUND: In 2008, Rwanda established an influenza sentinel surveillance (ISS)
      system to describe the epidemiology of influenza and monitor for the emergence of
      novel influenza A viruses. We report surveillance results from August 2008 to
      July 2010. METHODS: We conducted ISS by monitoring patients with influenza-like
      illness (ILI) and severe acute respiratory infection (SARI) at 6 hospitals. For
      each case, demographic and clinical data, 1 nasopharyngeal specimen, and 1
      oropharyngeal specimen were collected. Specimens were tested by real-time reverse
      transcription polymerase chain reaction for influenza A and B viruses at the
      National Reference Laboratory in Rwanda. RESULTS: A total of 1916 cases (945 ILI
      and 971 SARI) were identified. Of these, 29.2% (n = 276) of ILI and 10.4% (n =
      101) of SARI cases tested positive for influenza. Of the total influenza-positive
      cases (n = 377), 71.8% (n = 271) were A(H1N1) pdm09, 5.6% (n = 21) influenza
      A(H1), 7.7% (n = 29) influenza A(H3), 1.6% (n = 6) influenza A (unsubtyped), and
      13.3% (n = 50) influenza B. The percentage of positivity for influenza viruses
      was highest in October-November and February-March, during peaks in rainfall.
      CONCLUSIONS: The implementation of ISS enabled characterization of the
      epidemiology and seasonality of influenza in Rwanda for the first time. Future
      efforts should determine the population-based influenza burden to inform
      interventions such as targeted vaccination.

PMID- 23169978
TI  - Clinic- and hospital-based sentinel influenza surveillance, Uganda 2007-2010.
AB  - BACKGROUND: To assess the epidemiology and seasonality of influenza in Uganda, we
      established a sentinel surveillance system for influenza in 5 hospitals and 5
      outpatient clinics in 4 geographically distinct regions, using standard case
      definitions for influenzalike illness (ILI) and severe acute respiratory illness
      (SARI). METHODS: Nasopharyngeal and oropharyngeal specimens were collected from
      April 2007 through September 2010 from patients with ILI and SARI aged >= 2
      months, tested for influenza A and B with real-time reverse-transcription
      polymerase chain reaction, and subtyped for seasonal A/H1, A/H3, A/H5, and 2009
      pandemic influenza A (pH1N1). RESULTS: Among the 2758 patients sampled, 2656
      (96%) enrolled with ILI and 101 (4%) with SARI. Specimens from 359 (13.0%) were
      positive for influenza; 267 (74.4%) were influenza A, and 92 (25.6%) were
      influenza B. The median age of both patients with ILI and patients with SARI was
      4 years (range, 2 months to 67 years); patients aged 5-14 years had the highest
      influenza-positive percentage (19.6%), and patients aged 0-4 years had the lowest
      percentage (9.1%). Influenza circulated throughout the year, but the percentage
      of influenza-positive specimens peaked during June-November, coinciding with the
      second rainy season. CONCLUSIONS: Continued and increased surveillance is needed
      to better understand the morbidity and mortality of influenza in Uganda.

PMID- 23169971
TI  - Molecular characterization and phylogenetic analysis of the hemagglutinin 1
      protein of human influenza A virus subtype H1N1 circulating in Kenya during 2007
      2008.
AB  - BACKGROUND: Among influenza viruses, type A viruses exhibit the greatest genetic
      diversity, infect the widest range of host species, and cause the vast majority
      of cases of severe disease in humans, including cases during the great pandemics.
      The hemagglutinin 1 (HA1) domain of the HA protein contains the highest
      concentration of epitopes and, correspondingly, experiences the most intense
      positive selection pressure. OBJECTIVES: We sought to isolate and genetically
      characterize influenza A virus subtype H1N1 (A[H1N1]) circulating in Kenya during
      2007-2008, using the HA1 protein. METHODS: Nasopharyngeal swab specimens were
      collected from patients aged >= 2 months who presented to 8 healthcare facilities
      in Kenya with influenza-like illness. We tested specimens for seasonal influenza
      A viruses, using real-time reverse-transcription polymerase chain reaction (RT
      PCR). Viruses were subtyped using subtype-specific primers. Specimens positive
      for seasonal A(H1N1) were inoculated onto Madin-Darby canine kidney cells for
      virus isolation. Viral RNAs were extracted from isolates, and the HA1 gene was
      amplified by RT-PCR, followed by nucleotide sequencing. Nucleotide sequences were
      assembled using BioEdit and translated into amino acid codes, using DS Gene,
      version 1.5. Multiple sequence alignments were performed using MUSCLE, version
      3.6, and phylogenetic analysis was performed using MrBayes software. RESULTS: We
      found that, similar to A/Brisbane/59/2007 (H1N1)-like virus, which was included
      in the southern hemisphere vaccine for the 2009 influenza season, all 2007 Kenyan
      viruses had D39N, R77K, T132V, K149R, and E277K amino acid substitutions,
      compared with A/Solomon Islands/3/2006 (H1N1)-like virus, a component of the
      southern hemisphere vaccine for the 2008 influenza season. However, the majority
      of 2008 viruses from Kenya also had R192K and R226Q substitutions, compared with
      A/Solomon Islands/3/2006 (H1N1)-like virus. These 2 changes occurred at the
      receptor binding site. The majority of the 2008 Kenyan isolates contained N187S,
      G189N, and A193T mutations, which differed from A/Brisbane/59/2007 (H1N1)-like
      virus. The A193T substitution is involved in binding the sialic acid receptor.
      Phylogenetically, the 2008 Kenyan isolates grouped into 2 clusters. The main
      cluster contained viruses with N187S and A193T changes; residue 187 is involved
      in receptor binding, whereas residue 193 is at antigenic site Sb. CONCLUSION:
      Overall, the major genetic variations that occurred in seasonal A(H1) viruses
      either affected receptor binding or altered epitopes at the immunodominant sites.
      These genetic variations in seasonal A(H1N1) isolated in Kenya during 2007-2008
      highlight the importance of continuing surveillance and characterization of
      emerging drift variants of influenza virus in Africa.

PMID- 23169980
TI  - Heart failure: not just the heart but also the lungs.

PMID- 23169979
TI  - 2009 Pandemic influenza A virus subtype H1N1 in Morocco, 2009-2010: epidemiology,
      transmissibility, and factors associated with fatal cases.
AB  - BACKGROUND: Following the emergence of 2009 pandemic influenza A virus subtype
      H1N1 (A[H1N1]pdm09) in the United States and Mexico in April 2009, A(H1N1)pdm09
      spread rapidly all over the world. There is a dearth of information about the
      epidemiology of A(H1N1)pdm09 in Africa, including Morocco. We describe the
      epidemiologic characteristics of the A(H1N1)pdm09 epidemic in Morocco during 2009
      2010, including transmissibility and risk factors associated with fatal disease.
      METHODS: We implemented influenza surveillance for patients presenting with
      influenza-like illness (ILI) at 136 private and public clinics for patients with
      severe acute respiratory illness (SARI) at 16 regional public hospitals from June
      2009 through February 2010. Respiratory samples and structured questionnaires
      were collected from all enrolled patients, and samples were tested by real-time
      reverse-transcription polymerase chain reaction for influenza viruses. We
      estimated the risk factors associated with fatal disease as well as the basic
      reproduction number (R(0)) and the serial interval of the pandemic virus.
      RESULTS: From June 2009 through February 2010, we obtained 3937 specimens, of
      which 1452 tested positive for influenza virus. Of these, 1398 (96%) were
      A(H1N1)pdm09. Forty percent of specimens from ILI cases (1056 of 2646) and 27%
      from SARI cases (342 of 1291) were positive for A(H1N1)pdm09. Sixty-four deaths
      occurred among laboratory-confirmed A(H1N1)pdm09 SARI cases. Among these cases,
      those who had hypertension (age-adjusted odd ratio [aOR], 28.2; 95% confidence
      interval [CI], 2.0-398.7), had neurological disorders (aOR, 7.5; 95% CI, 1.5
      36.4), or were obese (aOR, 7.1; 95% CI, 1.6-31.1), as well as women of
      gestational age who were pregnant (aOR, 2.5; 95% CI, 1.1-5.6), were at increased
      risk of death. Across the country, elevated numbers of locally acquired
      infections were detected 4 months after the detection of the first laboratory
      confirmed case and coincided with the expected influenza season (October-January)
      in Morocco. We obtained an R(0) estimate of 1.44 (95% CI, 1.32-1.56) and a mean
      serial interval (+/-SD) of 2.3 +/- 1.4 days (95% CI, 1.6-3.0). CONCLUSION:
      Widespread but delayed community transmission of A(H1N1)pdm09 occurred in Morocco
      in 2009, and A(H1N1)pdm09 became the dominant influenza virus subtype during the
      2009-2010 influenza season. The transmissibility characteristics were similar to
      those observed in other countries.

PMID- 23169981
TI  - Cardiac dysfunction and preeclampsia: can imaging give clues to mechanism?

PMID- 23169983
TI  - Three-dimensional reconstruction of the functional strain-line pattern in the
      left ventricle from 3-dimensional echocardiography.

PMID- 23169982
TI  - Multimodality imaging of lower extremity peripheral arterial disease: current
      role and future directions.

PMID- 23169984
TI  - Letter by Bourantas et al regarding article, "nonculprit plaques in patients with
      acute coronary syndromes have more vulnerable features compared with those with
      non-acute coronary syndromes: a 3-vessel optical coherence tomography study".

PMID- 23169985
TI  - Randomized assessment of ticagrelor versus prasugrel antiplatelet effects in
      patients with ST-segment-elevation myocardial infarction.
AB  - BACKGROUND: Ticagrelor and prasugrel provide stronger platelet inhibition
      compared with clopidogrel. Direct pharmacodynamic comparison between them has not
      yet been reported in ST-segment-elevation myocardial infarction patients. METHODS
      AND RESULTS: In a prospective, single-center, single-blind study, 55 out of 117
      (47%) screened consecutive ST-segment-elevation myocardial infarction patients
      undergoing primary percutaneous coronary intervention were randomized to either
      ticagrelor 180 mg loading followed by 90 mg bid, or prasugrel 60 mg loading
      followed by 10 mg od for 5 days. Platelet reactivity (PR) was assessed with the
      VerifyNow P2Y12 function assay and the Multiplate Analyzer at 0, 1, 2, 6, 24
      hours, and 5 days postrandomization. The primary end point, PR with VerifyNow at
      hour 1, did not differ significantly between patients randomized to ticagrelor
      versus prasugrel (257.3 P2Y12 reaction unit [PRU], 95% CI 230.8-283.8 versus
      231.3 PRU, 95% CI 205.3-257.4; P=0.2). PR did not differ at 2, 6, and 24 hours,
      although at day 5 it was lower with ticagrelor than prasugrel (25.6 PRU, 95% CI
      12.3-38.9 versus 50.3 PRU, 95% CI 36.4-64.1; P=0.01). At hour 2, high on
      treatment PR rates (cutoff 208 PRU) were 46.2% and 34.6% for ticagrelor and
      prasugrel, respectively, decreased significantly thereafter, whereas did not
      differ significantly between the 2 agents at all the time points of the study.
      CONCLUSIONS: In patients with ST-segment-elevation myocardial infarction
      undergoing primary percutaneous coronary intervention, both ticagrelor and
      prasugrel exhibit an initial delay in the onset of their antiplatelet action.
      Ticagrelor did not appear superior to prasugrel in reducing PR during the first
      24 hours of ST-segment-elevation myocardial infarction. CLINICAL TRIAL
      REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01463163.

PMID- 23169986
TI  - Predictors of clinical outcomes in patients with severe aortic stenosis
      undergoing TAVI: a multistate analysis.
AB  - BACKGROUND: Patients with severe aortic stenosis at increased surgical risk
      continue to experience compromised long-term survival despite successful
      transcatheter aortic valve implantation. We used time-related pathways in a
      multistate analysis to identify predictors of adverse long-term outcome in
      patients who underwent transcatheter aortic valve implantation. METHODS AND
      RESULTS: In a cohort of 389 patients with a mean age of 82.4 +/- 5.8 years and a
      STS score of 6.8 +/- 5.3 undergoing transcatheter aortic valve implantation
      between 2007 and 2011, multistate analysis was used to estimate mortality and
      stroke taking into account intercurrent events including kidney injury and the
      composite of access site and bleeding complications (ABC). Transapical access
      emerged as a predictor of kidney injury (hazard ratio [HR], 2.12; 95% confidence
      interval [CI] 1.00-4.47) and ABC (HR, 1.78; 95% CI, 1.07-2.96), but had no impact
      on the risk of stroke or death. Body mass index <=20 kg/m(2) increased the risk
      of stroke or death (HR, 2.64; 95% CI, 1.25-5.54). Age >80 years (HR, 3.15; 95%
      CI, 1.11-8.92), body mass index <=20 kg/m(2) (HR, 4.11; 95% CI, 1.33-12.70),
      prior stroke (HR, 16.42; 95% CI, 3.63-74.21), and presence of atrial fibrillation
      at baseline (HR, 4.12; 95% CI, 1.87-9.97) increased the risk of stroke and death
      after an intercurrent event of ABC. CONCLUSIONS: A body mass index <=20 kg/m(2)
      was identified as a primary predictor of stroke and death after transcatheter
      aortic valve implantation during long-term follow-up, whereas transapical access
      emerged as a predictor of kidney injury and ABC. Age >80 years, body mass index
      <=20 kg/m(2), prior stroke, and presence of atrial fibrillation at baseline
      increased the risk of stroke and death after an intercurrent event of ABC.

PMID- 23169991
TI  - Meta-analysis of the relationship between dose and benefit in phase I targeted
      agent trials.
AB  - BACKGROUND: To date, the primary objective of phase I trials has been to safely
      select the maximum tolerated dose (MTD) of a drug or drug combination for
      utilization in subsequent trials. Although conventional cytotoxic chemotherapy is
      generally more effective at the MTD than molecularly targeted agents (MTAs),
      recent single-institution data suggest that molecularly targeted agent may not
      require an MTD for efficacy. We analyzed patient outcome results in MTA phase I
      trials at multiple institutions throughout North America sponsored by the
      National Cancer Institute's Cancer Therapy Evaluation Program. METHODS: We
      retrospectively collected and analyzed data on patients treated on monotherapy
      phase I trials investigating novel MTAs with a defined MTD from 2000 to 2009.
      Logistic regression analysis was used to test whether there was an increase in
      the probability of a response as dose increased. A Cox proportional hazards model
      was used to determine if overall survival increased with increasing dose. All
      statistical tests were two-sided. RESULTS: We analyzed 1908 patients treated on
      55 eligible clinical trials. The probability of both overall response (complete
      response plus partial response) and overall survival increased with increasing
      dose (odds ratio for increased response = 1.56, P = .10; hazard ratio for death =
      0.37, P = .008) when controlling for study as a covariate. CONCLUSIONS: Patients
      treated in the context of phase I trials with MTAs continue to derive reasonable
      clinical benefit. Contrary to other single institution data, our data suggest
      clinical benefit in terms of increasing response and overall survival with
      increasing dose.

PMID- 23169992
TI  - SIRT1 represses estrogen-signaling, ligand-independent ERalpha-mediated
      transcription, and cell proliferation in estrogen-responsive breast cells.
AB  - In prostate and breast cancer, the androgen receptor and estrogen receptor (ER)
      mediate induction of androgen- and estrogen-responsive genes respectively and
      stimulate cell proliferation in response to the binding of their cognate steroid
      hormones. Sirtuin 1 (SIRT1) is a NAD+-dependent class III histone deacetylase
      that has been linked to gene silencing, control of the cell cycle, apoptosis, and
      energy homeostasis. In prostate cancer, SIRT1 is required for androgen antagonist
      mediated transcriptional repression and growth suppression of prostate cancer
      cells. Whether SIRT1 plays a similar role in the actions of estrogen or
      antagonists had not been determined. We report here that SIRT1 represses the
      transcriptional and proliferative response of breast cancer cells to estrogens,
      and this repression is ERalpha dependent. Inhibition of SIRT1 activity results in
      the phosphorylation of ERalpha in an AKT-dependent manner, and this activation
      requires phosphoinositide 3-kinase activity. Phosphorylated ERalpha subsequently
      accumulates in the nucleus, where ERalpha binds DNA ER-responsive elements and
      activates transcription of estrogen-responsive genes. This ER-dependent
      transcriptional activation augments estrogen-induced signaling, but also
      activates ER signaling in the absence of estrogen, thus defining a novel and
      unexpected mechanism of ligand-independent ERalpha-mediated activation and target
      gene transcription. Like ligand-dependent activation of ERalpha, SIRT1 inhibition
      mediated ERalpha activation in the absence of estrogen also results in breast
      cancer cell proliferation. Together, these data demonstrate that SIRT1 regulates
      the most important cell signaling pathway for the growth of breast cancer cells,
      both in the presence and the absence of estrogen.

PMID- 23169993
TI  - Optimization of large field tritan stimuli using concentric isoluminant annuli.
AB  - Large, nominally isoluminant chromatic gratings containing a short-wavelength
      component are prone to luminance contrast intrusions due to retinal
      inhomogeneity, especially as a result of the uneven distribution of macular
      pigment. Isoluminance is usually determined for a relatively small, central area,
      but a significantly larger stimulus cannot be isoluminant across the whole field,
      largely due to macular pigment absorption of short-wavelength light. This
      confounds attempts to maintain high selectivity, particularly in suprathreshold
      electrophysiological and brain-imaging studies that require large stimulus
      fields. Here we introduce the concept of a panisoluminant grating (PIG), which
      comprises a series of concentric annular regions, each adjusted to location
      specific isoluminance for the observer. Gratings were modulated along subject
      specific tritanopic confusion lines and the selectivity of responses to the PIG
      was tested according to both psychophysical and electrophysiological criteria.
      The psychophysically-determined temporal tuning function obtained using the PIG
      showed lower sensitivity and lower resolution than with a conventional tritan
      grating of equal diameter (18 degrees ). Chromatic onset visual evoked potentials
      (VEPs) to the PIG were dominated by a chromatic-specific negative wave and
      reduced achromatic response components that were prominent in VEPs to the
      conventional grating. These data demonstrate that a large tritan PIG is capable
      of eliciting selective responses of the S-cone-driven pathway at threshold and at
      suprathreshold levels. The PIG stimulus may prove beneficial in investigations
      that require large fields such as electrophysiological and brain imaging studies
      of chromatic processing.

PMID- 23169994
TI  - The furrow illusion: peripheral motion becomes aligned with stationary contours.
AB  - A spot moved vertically up and down across a background grating that was tilted
      at 45 degrees . In foveal vision this was seen accurately, but when viewed
      peripherally the spot's path was perceptually attracted toward the grating
      orientation, and at large eccentricities (>20 degrees ) the spot appeared to move
      at 45 degrees , parallel to the grating. The intersections between the grating
      and the moving spot drive this illusion, revealing profound differences between
      fovea and periphery in processing visual motion.

PMID- 23169995
TI  - A novel method for comparative analysis of retinal specialization traits from
      topographic maps.
AB  - Vertebrates possess different types of retinal specializations that vary in
      number, size, shape, and position in the retina. This diversity in retinal
      configuration has been revealed through topographic maps, which show variations
      in neuron density across the retina. Although topographic maps of about 300
      vertebrates are available, there is no method for characterizing retinal traits
      quantitatively. Our goal is to present a novel method to standardize information
      on the position of the retinal specializations and changes in retinal ganglion
      cell (RGC) density across the retina from published topographic maps. We measured
      the position of the retinal specialization using two Cartesian coordinates and
      the gradient in cell density by sampling ganglion cell density values along four
      axes (nasal, temporal, ventral, and dorsal). Using this information, along with
      the peak and lowest RGC densities, we conducted discriminant function analyses
      (DFAs) to establish if this method is sensitive to distinguish three common types
      of retinal specializations (fovea, area, and visual streak). The discrimination
      ability of the model was higher when considering terrestrial (78%-80% correct
      classification) and aquatic (77%-86% correct classification) species separately
      than together. Our method can be used in the future to test specific hypotheses
      on the differences in retinal morphology between retinal specializations and the
      association between retinal morphology and behavioral and ecological traits using
      comparative methods controlling for phylogenetic effects.

PMID- 23169996
TI  - Gustatory habituation in Drosophila relies on rutabaga (adenylate cyclase)
      dependent plasticity of GABAergic inhibitory neurons.
AB  - In some situations, animals seem to ignore stimuli which in other contexts elicit
      a robust response. This attenuation in behavior, which enables animals to ignore
      a familiar, unreinforced stimulus, is called habituation. Despite the ubiquity of
      this phenomenon, it is generally poorly understood in terms of the underlying
      neural circuitry. Hungry fruit flies show a proboscis extension reflex (PER) when
      sensory receptors are stimulated by sugars. The PER is usually followed by
      feeding. However, if feeding is disallowed following sugar stimulation, PER is no
      longer robust, and the animal is considered to be habituated to this stimulus.
      Our results suggest that PER habituation requires an adenylate cyclase-dependent
      enhancement of inhibitory output of GABAergic neurons in the subesophageal
      ganglion (SOG), which mediates PER. GABA synthesis in and release from glutamic
      acid decarboxylase (GAD1) expressing neurons is necessary, and GABA(A) receptors
      on cholinergic neurons are required for PER habituation. The proposed inhibitory
      potentiation requires glutamate/NMDA-receptor signaling, possibly playing a role
      in stimulus selectivity. We explain why these data provide significant and
      independent support for a general model in which inhibitory potentiation
      underlies habituation in multiple neural systems and species.

PMID- 23169997
TI  - Interaction of lipocalin 2, transferrin, and siderophores determines the
      replicative niche of Klebsiella pneumoniae during pneumonia.
AB  - Pathogenic bacteria require iron for replication within their host. Klebsiella
      pneumoniae and other Gram-negative pathogens produce the prototypical siderophore
      enterobactin (Ent) to scavenge iron in vivo. In response, mucosal surfaces
      secrete lipocalin 2 (Lcn2), an innate immune protein that binds Ent to disrupt
      bacterial iron acquisition and promote acute inflammation during colonization. A
      subset of K. pneumoniae isolates attempt to evade Lcn2 by producing glycosylated
      Ent (Gly-Ent, salmochelin) or the alternative siderophore yersiniabactin (Ybt).
      However, these siderophores are not functionally equivalent and differ in their
      abilities to promote growth in the upper respiratory tract, lungs, and serum. To
      understand how Lcn2 exploits functional differences between siderophores,
      isogenic mutants of an Ent(+) Gly-Ent(+) Ybt(+) K. pneumoniae strain were
      inoculated into Lcn2(+/+) and Lcn2(-/-) mice, and the pattern of pneumonia was
      examined. Lcn2 effectively protected against the iroA ybtS mutant (Ent(+) Gly
      Ent(-) Ybt(-)). Lcn2(+/+) mice had small foci of pneumonia, whereas Lcn2(-/-)
      mice had many bacteria in the perivascular space. The entB mutant (Ent(-) Ybt(+)
      Gly-Ent(-)) caused moderate bronchopneumonia but did not invade the transferrin
      containing perivascular space. Accordingly, transferrin blocked Ybt-dependent
      growth in vitro. The wild type and the iroA mutant, which both produce Ent and
      Ybt, had a mixed phenotype, causing a moderate bronchopneumonia in Lcn2(+/+) mice
      and perivascular overgrowth in Lcn2(-/-) mice. Together, these data indicate that
      Lcn2, in combination with transferrin, confines K. pneumoniae to the airways and
      prevents invasion into tissue containing the pulmonary vasculature. IMPORTANCE:
      Gram-negative bacteria are a common cause of severe hospital-acquired infections.
      To cause disease, they must obtain iron and secrete the small molecule
      enterobactin to do so. Animal models of pneumonia using Klebsiella pneumoniae
      indicate that enterobactin promotes severe disease. Accordingly, the host defense
      protein lipocalin 2 exploits this common target by binding enterobactin and
      disrupting its function. However, pathogenic bacteria often make additional
      siderophores that lipocalin 2 cannot bind, such as yersiniabactin, which could
      make this host defense ineffective. This work compares the pattern and severity
      of pneumonia caused by K. pneumoniae based on which siderophores it produces. The
      results indicate that enterobactin promotes growth around blood vessels that are
      rich in the iron-binding protein transferrin, but yersiniabactin does not.
      Together, transferrin and lipocalin 2 protect this space against all types of K.
      pneumoniae tested. Therefore, the ability to acquire iron determines where
      bacteria can grow in the lung.

PMID- 23169999
TI  - Unexpected diversity of signal peptides in prokaryotes.
AB  - Signal peptides are a cornerstone mechanism for cellular protein localization,
      yet until now experimental determination of signal peptides has come from only a
      narrow taxonomic sampling. As a result, the dominant view is that Sec-cleaved
      signal peptides in prokaryotes are defined by a canonical AxA motif. Although
      other residues are permitted in the motif, alanine is by far the most common.
      Here we broadly examine proteomics data to reveal the signal peptide sequences
      for 32 bacterial and archaeal organisms from nine phyla and demonstrate that this
      alanine preference is not universal. Discoveries include fundamentally distinct
      signal peptide motifs from Alphaproteobacteria, Spirochaetes, Thermotogae and
      Euryarchaeota. In these novel motifs, alanine is no longer the dominant residue
      but has been replaced in a different way for each taxon. Surprisingly, divergent
      motifs correlate with a proteome-wide reduction in alanine. Computational
      analyses of ~1,500 genomes reveal numerous major evolutionary clades which have
      replaced the canonical signal peptide sequence with novel motifs. IMPORTANCE:
      This article replaces a widely held general model with a more detailed model
      describing phylogenetically correlated variation in motifs for Sec secretion.

PMID- 23169998
TI  - Riboswitches for intracellular study of genes involved in Francisella
      pathogenesis.
AB  - The study of many important intracellular bacterial pathogens requires an
      understanding of how specific virulence factors contribute to pathogenesis during
      the infection of host cells. This requires tools to dissect gene function, but
      unfortunately, there is a lack of such tools for research on many difficult-to
      study, or understudied, intracellular pathogens. Riboswitches are RNA-based
      genetic control elements that directly modulate gene expression upon ligand
      binding. Here we report the application of theophylline-sensitive synthetic
      riboswitches to induce protein expression in the intracellular pathogen
      Francisella. We show that this system can be used to activate the bacterial
      expression of the reporter beta-galactosidase during growth in rich medium.
      Furthermore, we applied this system to control the expression of green
      fluorescent protein during intracellular infection by the addition of
      theophylline directly to infected macrophages. Importantly, we could control the
      expression of a novel endogenous protein required for growth under nutrient
      limiting conditions and replication in macrophages, FTN_0818. Riboswitch-mediated
      control of FTN_0818 rescued the growth of an FTN_0818 mutant in minimal medium
      and during macrophage infection. This is the first demonstration of the use of a
      synthetic riboswitch to control an endogenous gene required for a virulence trait
      in an intracellular bacterium. Since this system can be adapted to diverse
      bacteria, the ability to use riboswitches to regulate intracellular bacterial
      gene expression will likely facilitate the in-depth study of the virulence
      mechanisms of numerous difficult-to-study intracellular pathogens such as
      Ehrlichia chaffeensis, Anaplasma phagocytophilum, and Orientia tsutsugamushi, as
      well as future emerging pathogens. IMPORTANCE: Determining how specific bacterial
      genes contribute to virulence during the infection of host cells is critical to
      understanding how pathogens cause disease. This can be especially challenging
      with many difficult-to-study intracellular pathogens. Riboswitches are RNA-based
      genetic control elements that can be used to help dissect gene function,
      especially since they can be used in a broad range of bacteria. We demonstrate
      the utility of riboswitches, and for the first time show that riboswitches can be
      used to functionally control a bacterial gene that is critical to the ability of
      a pathogen to cause disease, during intracellular infection. Since this system
      can be adapted to diverse bacteria, riboswitches will likely facilitate the in
      depth study of the virulence mechanisms of numerous difficult-to-study
      intracellular pathogens, as well as future emerging pathogens.

PMID- 23170000
TI  - The membrane-proximal region (MPR) of herpes simplex virus gB regulates
      association of the fusion loops with lipid membranes.
AB  - Glycoprotein B (gB), gD, and gH/gL constitute the fusion machinery of herpes
      simplex virus (HSV). Prior studies indicated that fusion occurs in a stepwise
      fashion whereby the gD/receptor complex activates the entire process, while gH/gL
      regulates the fusion reaction carried out by gB. Trimeric gB is a class III
      fusion protein. Its ectodomain of 773 amino acids contains a membrane-proximal
      region (MPR) (residues 731 to 773) and two fusion loops (FLs) per protomer. We
      hypothesized that the highly hydrophobic MPR interacts with the FLs, thereby
      masking them on virions until fusion begins. To test this hypothesis, we made a
      series of deletion, truncation, and point mutants of the gB MPR. Although the
      full-length deletion mutants were expressed in transfected cells, they were not
      transported to the cell surface, suggesting that removal of even small stretches
      of the MPR was highly detrimental to gB folding. To circumvent this limitation,
      we used a baculovirus expression system to generate four soluble proteins, each
      lacking the transmembrane region and cytoplasmic tail. All retained the FLs and
      decreasing portions of the MPR [gB(773t) (gB truncated at amino acid 773),
      gB(759t), gB(749t), and gB(739t)]. Despite the presence of the FLs, all were
      compromised in their ability to bind liposomes compared to the control, gB(730t),
      which lacks the MPR. We conclude that residues 731 to 739 are sufficient to mask
      the FLs, thereby preventing liposome association. Importantly, mutation of two
      aromatic residues (F732 and F738) to alanine restored the ability of gB(739t) to
      bind liposomes. Our data suggest that the MPR is important for modulating the
      association of gB FLs with target membranes. IMPORTANCE To successfully cause
      disease, a virus must infect host cells. Viral infection is a highly regulated,
      multistep process. For herpesviruses, genetic material transfers from the virus
      to the target cell through fusion of the viral and host cell lipid membranes.
      Here, we provide evidence that the ability of the herpes simplex virus (HSV)
      glycoprotein B (gB) fusion protein to interact with the host membrane is
      regulated by its membrane-proximal region (MPR), which serves to cover or shield
      its lipid-associating moieties (fusion loops). This in turn prevents the
      premature binding of gB with host cells and provides a level of regulation to the
      fusion process. These findings provide important insight into the complex
      regulatory steps required for successful herpesvirus infection.

PMID- 23170001
TI  - Genetic analysis of a vancomycin-resistant Staphylococcus aureus strain isolated
      in Iran.

PMID- 23170003
TI  - Can start-ups finish up?

PMID- 23170004
TI  - Origins of medical innovation: the case of coronary artery stents.

PMID- 23170002
TI  - Genomic characterization of a newly discovered coronavirus associated with acute
      respiratory distress syndrome in humans.
AB  - A novel human coronavirus (HCoV-EMC/2012) was isolated from a man with acute
      pneumonia and renal failure in June 2012. This report describes the complete
      genome sequence, genome organization, and expression strategy of HCoV-EMC/2012
      and its relation with known coronaviruses. The genome contains 30,119 nucleotides
      and contains at least 10 predicted open reading frames, 9 of which are predicted
      to be expressed from a nested set of seven subgenomic mRNAs. Phylogenetic
      analysis of the replicase gene of coronaviruses with completely sequenced genomes
      showed that HCoV-EMC/2012 is most closely related to Tylonycteris bat coronavirus
      HKU4 (BtCoV-HKU4) and Pipistrellus bat coronavirus HKU5 (BtCoV-HKU5), which
      prototype two species in lineage C of the genus Betacoronavirus. In accordance
      with the guidelines of the International Committee on Taxonomy of Viruses, and in
      view of the 75% and 77% amino acid sequence identity in 7 conserved replicase
      domains with BtCoV-HKU4 and BtCoV-HKU5, respectively, we propose that HCoV
      EMC/2012 prototypes a novel species in the genus Betacoronavirus. HCoV-EMC/2012
      may be most closely related to a coronavirus detected in Pipistrellus
      pipistrellus in The Netherlands, but because only a short sequence from the most
      conserved part of the RNA-dependent RNA polymerase-encoding region of the genome
      was reported for this bat virus, its genetic distance from HCoV-EMC remains
      uncertain. HCoV-EMC/2012 is the sixth coronavirus known to infect humans and the
      first human virus within betacoronavirus lineage C. IMPORTANCE: Coronaviruses are
      capable of infecting humans and many animal species. Most infections caused by
      human coronaviruses are relatively mild. However, the outbreak of severe acute
      respiratory syndrome (SARS) caused by SARS-CoV in 2002 to 2003 and the fatal
      infection of a human by HCoV-EMC/2012 in 2012 show that coronaviruses are able to
      cause severe, sometimes fatal disease in humans. We have determined the complete
      genome of HCoV-EMC/2012 using an unbiased virus discovery approach involving next
      generation sequencing techniques, which enabled subsequent state-of-the-art
      bioinformatics, phylogenetics, and taxonomic analyses. By establishing its
      complete genome sequence, HCoV-EMC/2012 was characterized as a new genotype which
      is closely related to bat coronaviruses that are distant from SARS-CoV. We expect
      that this information will be vital to rapid advancement of both clinical and
      vital research on this emerging pathogen.

PMID- 23170005
TI  - Shared decision making: a path toward improved patient-centered outcomes.

PMID- 23170008
TI  - The Institute of Medicine committee report "best care at lower cost: the path to
      continuously learning health care".

PMID- 23170006
TI  - Longitudinal study of implantable cardioverter-defibrillators: methods and
      clinical characteristics of patients receiving implantable cardioverter
      defibrillators for primary prevention in contemporary practice.
AB  - BACKGROUND: Implantable cardioverter-defibrillators (ICDs) are increasingly used
      for primary prevention after randomized, controlled trials demonstrating that
      they reduce the risk of death in patients with left ventricular systolic
      dysfunction. The extent to which the clinical characteristics and long-term
      outcomes of unselected, community-based patients with left ventricular systolic
      dysfunction undergoing primary prevention ICD implantation in a real-world
      setting compare with those enrolled in the randomized, controlled trials is not
      well characterized. This study is being conducted to address these questions.
      METHODS AND RESULTS: The study cohort includes consecutive patients undergoing
      primary prevention ICD placement between January 1, 2006 and December 31, 2009 in
      7 health plans. Baseline clinical characteristics were acquired from the National
      Cardiovascular Data Registry ICD Registry. Longitudinal data collection is
      underway, and will include hospitalization, mortality, and resource use from
      standardized health plan data archives. Data regarding ICD therapies will be
      obtained through chart abstraction and adjudicated by a panel of experts in
      device therapy. Compared with the populations of primary prevention ICD therapy
      randomized, controlled trials, the cohort (n=2621) is on average significantly
      older (by 2.5-6.5 years), more often female, more often from racial and ethnic
      minority groups, and has a higher burden of coexisting conditions. The cohort is
      similar, however, to a national population undergoing primary prevention ICD
      placement. CONCLUSIONS: Patients undergoing primary prevention ICD implantation
      in this study differ from those enrolled in the randomized, controlled trials
      that established the efficacy of ICDs. Understanding a broad range of health
      outcomes, including ICD therapies, will provide patients, clinicians, and policy
      makers with contemporary data to inform decision-making.

PMID- 23170007
TI  - From cardiovascular disease to cardiovascular health: a quiet revolution?

PMID- 23170009
TI  - Most important outcomes research papers on valvular heart disease.

PMID- 23170010
TI  - Glucose 6-phosphate dehydrogenase deficiency increases redox stress and
      moderately accelerates the development of heart failure.
AB  - BACKGROUND: Glucose 6-phosphate dehydrogenase (G6PD) is the most common deficient
      enzyme in the world. In failing hearts, G6PD is upregulated and generates reduced
      nicotinamide adenine dinucleotide phosphate (NADPH) that is used by the
      glutathione pathway to remove reactive oxygen species but also as a substrate by
      reactive oxygen species-generating enzymes. Therefore, G6PD deficiency might
      prevent heart failure by decreasing NADPH and reactive oxygen species production.
      METHODS AND RESULTS: This hypothesis was evaluated in a mouse model of human G6PD
      deficiency (G6PDX mice, ~40% normal activity). Myocardial infarction with 3
      months follow-up resulted in left ventricular dilation and dysfunction in both
      wild-type and G6PDX mice but significantly greater end diastolic volume and wall
      thinning in G6PDX mice. Similarly, pressure overload induced by transverse aortic
      constriction (TAC) for 6 weeks caused greater left ventricular dilation in G6PDX
      mice than wild-type mice. We further stressed transverse aortic constriction mice
      by feeding a high fructose diet to increase flux through G6PD and reactive oxygen
      species production and again observed worse left ventricular remodeling and a
      lower ejection fraction in G6PDX than wild-type mice. Tissue content of lipid
      peroxidation products was increased in G6PDX mice in response to infarction and
      aconitase activity was decreased with transverse aortic constriction, suggesting
      that G6PD deficiency increases myocardial oxidative stress and subsequent damage.
      CONCLUSIONS: Contrary to our hypothesis, G6PD deficiency increased redox stress
      in response to infarction or pressure overload. However, we found only a modest
      acceleration of left ventricular remodeling, suggesting that, in individuals with
      G6PD deficiency and concurrent hypertension or myocardial infarction, the risk
      for developing heart failure is higher but limited by compensatory mechanisms.

PMID- 23170011
TI  - Vitamin D as a protective factor in multiple sclerosis.
AB  - OBJECTIVE: To examine the association between 25-hydroxyvitamin D (25[OH]D)
      levels and the risk of multiple sclerosis (MS) in blood samples collected
      prospectively and during gestation. METHODS: In this nested case-control study, 2
      population-based biobanks with 291,500 samples from 164,000 persons collected
      since 1975 in the northern half of Sweden were used. We identified prospectively
      collected blood samples from MS cases (n = 192, controls matched 2:1) and
      gestational samples from pregnant mothers where the offspring had later developed
      MS (n = 37, control mothers matched 5:1). 25(OH)D levels were measured using an
      ELISA, and the risk of MS was analyzed using matched logistic regression.
      RESULTS: Levels of 25(OH)D >=75 (vs <75) nmol/L in prospectively collected blood
      samples were associated with a decreased risk of MS (odds ratio [OR] 0.39, 95%
      confidence interval [CI] 0.16-0.98). No decrease in MS risk was found in the
      offspring exposed to gestational 25(OH)D levels >=75 (vs <75) nmol/L (OR 1.8, 95%
      CI 0.53-5.8). The prevalence of 25(OH)D levels >=75 nmol/L in female controls
      decreased gradually during 1976-2005 (p trend = 0.005). CONCLUSION: This study
      supports the presence of an association between high 25(OH)D levels during the
      years preceding disease onset and a decreased risk of MS. In the very limited
      material with samples drawn in early pregnancy, where month-of-birth effects were
      controlled for, we found no association between gestational 25(OH)D levels and MS
      risk in the offspring. Decreasing 25(OH)D levels in the population may contribute
      to explain the increasing MS incidence that is suggested from epidemiologic
      studies.

PMID- 23170012
TI  - Neurologic disability: a hidden epidemic for India.
AB  - India, the world's second most populous country, is facing the emergence of a
      hitherto "hidden" epidemic: neurologic disability. The rapid economic,
      demographic, and social transformation of India in recent decades has already
      resulted in the double burden of unresolved epidemics of infectious diseases
      (e.g., malaria, tuberculosis) coupled with rising rates of chronic diseases
      (e.g., cardiovascular diseases). Neurologic disability is likely to join these
      public health concerns as a third epidemic, largely due to 3 emerging health
      trends: 1) an increase in traumatic brain injuries (TBI) from road traffic
      accidents (RTA); 2) an increase in the incidence of age-related dementia; and 3)
      an increase in the stroke incidence. Without adequate preparation, the treatment
      and long-term care for an increasing population of neurologically disabled people
      will strain India's health care system and economy in the coming years in
      unprecedented ways.

PMID- 23170013
TI  - Insulin-like growth factors in the brain and their potential clinical
      implications.
AB  - Insulin and insulin-like growth factors (IGFs) including IGF1 and IGF2 are
      members of the insulin-like peptide superfamily and have an important role in
      development, cell differentiation, plasticity, and survival of the nervous
      system. These insulin-like peptides act at several receptors that initiate
      downstream phosphorylation cascades that in turn regulate transcription, synaptic
      maturation, and apoptosis. In the adult brain, insulin and IGF1 act as
      circulating signals that reach the CNS by crossing the blood-brain barrier (BBB)
      or the blood-CSF barrier; IGF1 and IGF2 also act as paracrine signals released
      from all neural cells. The bioavailability of IGF1 and IGF2 is regulated by their
      binding to IGF binding proteins (IGFBPs). Insulin-like peptides participate in
      neuroprotection and may have an important role in the pathophysiology of several
      neurologic disorders and as potential therapeutic targets for these conditions.
      The insulin-like peptides, their receptors, effects in the nervous system, and
      potential clinical correlations have been the subject of several recent
      reviews.(1-6).

PMID- 23170014
TI  - Spontaneous keloid formation in patients with Bethlem myopathy.

PMID- 23170015
TI  - Stroke in sub-Saharan Africa: an urgent call for prevention.

PMID- 23170016
TI  - Simultaneous PML-IRIS after discontinuation of natalizumab in a patient with MS.

PMID- 23170017
TI  - Teaching neuroimages: subacute intracerebral hemorrhage mimicking brain tumor.

PMID- 23170018
TI  - Teaching video neuroimages: speech-induced oromandibular dystonia relieved by
      singing.

PMID- 23170019
TI  - Addressing the 100% of heart failure: a call for complete care of all ages.

PMID- 23170020
TI  - HFpEF: cardiovascular abnormalities not just comorbidities.

PMID- 23170021
TI  - Heart failure patients with low blood pressure: how should we manage
      neurohormonal blocking drugs?

PMID- 23170022
TI  - Response to Ryan and Parwani: heart failure patients with low blood pressure: how
      should we manage neurohormonal blocking drugs?

PMID- 23170023
TI  - Letter by Haufe et al regarding article, "Adipose tissue inflammation and
      adiponectin resistance in patients with advanced heart failure: correction after
      ventricular assist device implantation".

PMID- 23170024
TI  - Letter by Jennings regarding article, "Mechanisms of bleeding and approach to
      patients with axial-flow left ventricular assist devices".

PMID- 23170025
TI  - Sudden death in an infant with angina, restrictive cardiomyopathy, and coronary
      artery bridging: an unusual phenotype for a beta-myosin heavy chain (MYH7)
      sarcomeric protein mutation.

PMID- 23170026
TI  - Morphologic heterogeneity in left ventricular noncompaction resulting in
      accessory left ventricular chambers.

PMID- 23170027
TI  - Bench mitral valve repair of donor hearts before orthotopic heart
      transplantation.

PMID- 23170028
TI  - Letter by Palatini regarding article, "Habitual coffee consumption and risk of
      heart failure: a dose-response meta-analysis".

PMID- 23170031
TI  - Concomitant use of ipratropium and tiotropium in chronic obstructive pulmonary
      disease.
AB  - OBJECTIVE: To describe the current data evaluating the efficacy and safety of
      ipratropium used in combination with tiotropium in patients with chronic
      obstructive pulmonary disease. DATA SOURCES: A literature search using MEDLINE
      (1966-August 2012) and EMBASE (1973-August 2012) was conducted using the search
      terms ipratropium, tiotropium, combination drug therapy, and chronic obstructive
      pulmonary disease. References of identified articles were reviewed for additional
      relevant citations. STUDY SELECTION AND DATA EXTRACTION: All English-language
      articles regarding the concomitant use of ipratropium and tiotropium were
      reviewed. DATA SYNTHESIS: Two prospective randomized controlled trials have
      demonstrated increases in bronchodilation with ipratropium when added to
      maintenance tiotropium therapy, suggesting potential benefits during short-term,
      combined use. One study reported significantly higher peak forced expiratory
      volume in 1 second (FEV(1)) responses with both ipratropium (230 mL) and
      fenoterol (315 mL) compared to placebo (178 mL) when added to maintenance
      tiotropium. The peak response with fenoterol was significantly higher than with
      ipratropium (FEV(1) difference = 84 mL). Another study reported a mean difference
      in FEV(1) of 81 mL (95% CI 27 to 136) with albuterol versus placebo and a mean
      difference in FEV(1) of 68 mL (95% CI 3 to 132) with ipratropium versus placebo.
      The difference between albuterol and ipratropium when added to maintenance
      tiotropium was not significant. One large observational study reported a
      significantly higher risk of acute urinary retention in individuals receiving
      combination therapy with a short- and long-acting anticholinergic agent compared
      to those receiving monotherapy (OR 1.84; 95% CI 1.25 to 2.71). Individuals at
      highest risk were men and those with evidence of benign prostatic hypertrophy.
      CONCLUSIONS: While ipratropium may provide spirometric improvements in lung
      function for patients receiving tiotropium maintenance therapy, the clinical
      significance of these improvements has not been documented and the risk of
      anticholinergic adverse effects is increased with combination therapy. Further
      studies evaluating the safety and efficacy of concomitant ipratropium and
      tiotropium are warranted before combination use can be recommended for select
      patients.

PMID- 23170032
TI  - Effectiveness of palonosetron versus other serotonin 5-HT3 receptor antagonists
      in triple antiemetic regimens during multiday highly emetogenic chemotherapy.
AB  - BACKGROUND: The second-generation serotonin 5-HT(3) receptor antagonist
      palonosetron has shown improved efficacy in the prevention of both acute and
      delayed chemotherapy-induced nausea and vomiting (CINV). However, there have been
      no randomized controlled trials supporting the preferential use of palonosetron
      in triple antiemetic regimens for patients receiving multiday highly emetogenic
      chemotherapy (HEC). OBJECTIVE: To compare the effectiveness of palonosetron-based
      and first-generation 5-HT(3) receptor antagonist-based triple antiemetic regimens
      in cancer patients receiving multiday HEC. METHODS: This was a review and
      analysis of medical record data. A total of 115 patients who had received
      multiday HEC were included and grouped into a palonosetron-based antiemetic group
      (n = 73) or a first-generation 5-HT(3) receptor antagonist-based antiemetic group
      (n = 42). Data on CINV were collected in 24-hour intervals for 120 hours after
      the start of chemotherapy. RESULTS: Complete response rates did not differ
      significantly between the 2 groups during any of the 3 phases: acute (0-24
      hours), p = 0.877; overlap (24-120 hours), p = 0.997; and overall (0-120 hours),
      p = 0.723. The proportion of patients with complete control was similar between
      the groups during each phase: acute, p = 0.862; overlap, p = 0.838; and overall,
      p = 0.828. There was also no significant difference in other end points between
      the 2 groups. Among all patients, females experienced significantly more acute
      nausea (p = 0.040) and vomiting (p = 0.046) than males. Compared with
      nondrinkers, patients who consumed alcohol had a lower overall incidence of
      vomiting (p = 0.020). CONCLUSIONS: Within a triple antiemetic regimen, a
      palonosetron-based antiemetic regimen was not significantly different from
      regimens based on first-generation 5-HT(3) receptor antagonists in preventing
      CINV during multiday HEC.

PMID- 23170034
TI  - Association of genes with physiological functions by comparative analysis of
      pooled expression microarray data.
AB  - The physiological functions of a tissue in the body are carried out by its
      complement of expressed genes. Genes that execute a particular function should be
      more specifically expressed in tissues that perform the function. Given this
      premise, we mined public microarray expression data to build a database of genes
      ranked by their specificity of expression in multiple organs. The database
      permitted the accurate identification of genes and functions known to be specific
      to individual organs. Next, we used the database to predict transcriptional
      regulators of brown adipose tissue (BAT) and validated two candidate genes. Based
      upon hypotheses regarding pathways shared between combinations of BAT or white
      adipose tissue (WAT) and other organs, we identified genes that met threshold
      criteria for specific or counterspecific expression in each tissue. By
      contrasting WAT to the heart and BAT, the two most mitochondria-rich tissues in
      the body, we discovered a novel function for the transcription factor ESRRG in
      the induction of BAT genes in white adipocytes. Because the heart and other
      estrogen-related receptor gamma (ESRRG)-rich tissues do not express BAT markers,
      we hypothesized that an adipocyte co-regulator acts with ESRRG. By comparing WAT
      and BAT to the heart, brain, kidney and skeletal muscle, we discovered that an
      isoform of the transcription factor sterol regulatory element binding
      transcription factor 1 (SREBF1) induces BAT markers in C2C12 myocytes in the
      presence of ESRRG. The results demonstrate a straightforward bioinformatic
      strategy to associate genes with functions. The database upon which the strategy
      is based is provided so that investigators can perform their own screens.

PMID- 23170033
TI  - Prescription-acquired acetaminophen use and the risk of asthma in adults: a case
      control study.
AB  - BACKGROUND: Studies have examined the association between acetaminophen use and
      asthma; however, their interpretation is limited by several methodologic issues.
      OBJECTIVE: To investigate the association between recent and chronic prescription
      acquired acetaminophen use and asthma. METHODS: This retrospective case-control
      study used a 10% random sample of the IMS LifeLink commercial claims data from
      1997 to 2009. Cases had to have at least 1 incident claim of asthma; 3:1 controls
      matched on age, sex, and region were randomly chosen. Acetaminophen exposure,
      dose, and duration were measured in the 7- and 30-day (recent) and the 1-year
      (chronic) look-back periods. Multivariable conditional logistic regression was
      used to estimate the risk of asthma associated with acetaminophen use adjusted
      for comorbidities, other drugs increasing asthma risk, and health system factors.
      RESULTS: There were 28,892 cases and 86,676 controls, with mean age of 42.8
      years; 37.7% were males, and 22.6% of cases and 18.2% of controls had
      acetaminophen exposure in the pre-index year, with mean cumulative doses of 78.7
      g and 59.8 g, respectively. There was no significant association between recent
      prescription acetaminophen exposure and asthma (7 days: OR 1.02, p = 0.74; 30
      days: OR 0.97, p = 0.38). Cumulative prescription acetaminophen dose in the year
      prior increased asthma risk compared to acetaminophen nonusers (<=1 kg: OR 1.09,
      p < 0.001 and >1 kg: OR = 1.60, p = 0.02). Duration of prescription acetaminophen
      use greater than 30 days was associated with elevated asthma risk (OR 1.39, p <
      0.001). CONCLUSIONS: Chronic prescription-acquired acetaminophen use was
      associated with an increased risk of asthma, while recent use was not. However,
      over-the-counter acetaminophen use was not captured in this study and further
      epidemiologic research with complete acetaminophen exposure ascertainment and
      research on pathophysiologic mechanisms is needed to confirm these relationships.

PMID- 23170035
TI  - 11beta-HSD1 inhibition reduces atherosclerosis in mice by altering
      proinflammatory gene expression in the vasculature.
AB  - 11beta-Hydroxysteroid dehydrogenase type 1 (11beta-HSD1) is implicated in the
      etiology of metabolic syndrome. We previously showed that pharmacological
      inhibition of 11beta-HSD1 ameliorated multiple facets of metabolic syndrome and
      attenuated atherosclerosis in ApoE-/- mice. However, the molecular mechanism
      underlying the atheroprotective effect was not clear. In this study, we tested
      whether and how 11beta-HSD1 inhibition affects vascular inflammation, a major
      culprit for atherosclerosis and its associated complications. ApoE-/- mice were
      treated with an 11beta-HSD1 inhibitor for various periods of time. Plasma lipids
      and aortic cholesterol accumulation were quantified. Several microarray studies
      were carried out to examine the effect of 11beta-HSD1 inhibition on gene
      expression in atherosclerotic tissues. Our data suggest 11beta-HSD1 inhibition
      can directly modulate atherosclerotic plaques and attenuate atherosclerosis
      independently of lipid lowering effects. We identified immune response genes as
      the category of mRNA most significantly suppressed by 11beta-HSD1 inhibition.
      This anti-inflammatory effect was further confirmed in plaque macrophages and
      smooth muscle cells procured by laser capture microdissection. These findings in
      the vascular wall were corroborated by reduction in circulating MCP1 levels after
      11beta-HSD1 inhibition. Taken together, our data suggest 11beta-HSD1 inhibition
      regulates proinflammatory gene expression in atherosclerotic tissues of ApoE-/-
      mice, and this effect may contribute to the attenuation of atherosclerosis in
      these animals.

PMID- 23170037
TI  - Thermal acclimation of the symbiotic alga Symbiodinium spp. alleviates
      photobleaching under heat stress.
AB  - A moderate increase in seawater temperature causes coral bleaching, at least
      partially through photobleaching of the symbiotic algae Symbiodinium spp.
      Photobleaching of Symbiodinium spp. is primarily associated with the loss of
      light-harvesting proteins of photosystem II (PSII) and follows the inactivation
      of PSII under heat stress. Here, we examined the effect of increased growth
      temperature on the change in sensitivity of Symbiodinium spp. PSII inactivation
      and photobleaching under heat stress. When Symbiodinium spp. cells were grown at
      25 degrees C and 30 degrees C, the thermal tolerance of PSII, measured by the
      thermal stability of the maximum quantum yield of PSII in darkness, was commonly
      enhanced in all six Symbiodinium spp. tested. In Symbiodinium sp. CCMP827, it
      took 6 h to acquire the maximum PSII thermal tolerance after transfer from 25
      degrees C to 30 degrees C. The effect of increased growth temperature on the
      thermal tolerance of PSII was completely abolished by chloramphenicol, indicating
      that the acclimation mechanism of PSII is associated with the de novo synthesis
      of proteins. When CCMP827 cells were exposed to light at temperature ranging from
      25 degrees C to 35 degrees C, the sensitivity of cells to both high temperature
      induced photoinhibition and photobleaching was ameliorated by increased growth
      temperatures. These results demonstrate that thermal acclimation of Symbiodinium
      spp. helps to improve the thermal tolerance of PSII, resulting in reduced
      inactivation of PSII and algal photobleaching. These results suggest that whole
      organism coral bleaching associated with algal photobleaching can be at least
      partially suppressed by the thermal acclimation of Symbiodinium spp. at higher
      growth temperatures.

PMID- 23170036
TI  - The ubiquitin ligase PUB22 targets a subunit of the exocyst complex required for
      PAMP-triggered responses in Arabidopsis.
AB  - Plant pathogens are perceived by pattern recognition receptors, which are
      activated upon binding to pathogen-associated molecular patterns (PAMPs).
      Ubiquitination and vesicle trafficking have been linked to the regulation of
      immune signaling. However, little information exists about components of vesicle
      trafficking involved in immune signaling and the mechanisms that regulate them.
      In this study, we identified Arabidopsis thaliana Exo70B2, a subunit of the
      exocyst complex that mediates vesicle tethering during exocytosis, as a target of
      the plant U-box-type ubiquitin ligase 22 (PUB22), which acts in concert with
      PUB23 and PUB24 as a negative regulator of PAMP-triggered responses. We show that
      Exo70B2 is required for both immediate and later responses triggered by all
      tested PAMPs, suggestive of a role in signaling. Exo70B2 is also necessary for
      the immune response against different pathogens. Our data demonstrate that PUB22
      mediates the ubiquitination and degradation of Exo70B2 via the 26S Proteasome.
      Furthermore, degradation is regulated by the autocatalytic turnover of PUB22,
      which is stabilized upon PAMP perception. We therefore propose a mechanism by
      which PUB22-mediated degradation of Exo70B2 contributes to the attenuation of
      PAMP-induced signaling.

PMID- 23170038
TI  - ASSOCIATION OF HIV WITH BREAST ABSCESS AND ALTERED MICROBIAL SUSCEPTIBILITY
      PATTERNS.
AB  - BACKGROUND: Breast abscesses account for 15% of surgical day cases seen in the
      UTH. Nearly all of these cases occur in lactating women. Pre-natal HIV prevalence
      among women seeking care at UTH was estimated at 25% as of 2004. Baseline surveys
      have shown that up to 60% of soft tissue infections presenting to the UTH are HIV
      related.  OBJECTIVES: To determine if HIV infection is a risk factor for the
      development of breast abscesses in women presenting to the University Teaching
      Hospital (UTH) in Lusaka, Zambia. Secondary objective was to identify
      bacteriological aetiologies and drug sensitivity patterns associated with breast
      abscesses at UTH.  STUDY DESIGN: A case-control study of 110 consecutive breast
      feeding mothers diagnosed with breast abscess upon presentation to the UTH
      surgical service (cases) and 110 representative controls recruited from the UTH
      postnatal clinic.  MAIN OUTCOMES: HIV seropositivity and CD4 counts (if HIV
      positive) among cases and controls.  RESULTS: Fifty-four out of 110 (49.1%)
      lactating women with breast abscess had positive serologic tests for HIV. Only 25
      of 110 (23%) control women tested HIV positive. This difference was statistically
      significant, with an odds ratio of 3.28 (95% CI 1.83 - 5.87; p = 0.001). Mean CD4
      counts in cases were lower than in controls (338 vs. 568, p<0.001).
      Staphyloccocus aureus was the main causative agent (91.8%) of isolates. Among S.
      aureus isolates, 70 of 101 (69.3%) were oxacillin susceptible. Forty-three of 50
      (86.0%) specimens from HIV positive patients were resistant to SMX-TMP compared
      with only 61% of specimens from HIV negative patients (p=0.004).  CONCLUSIONS:
      HIV infection appears to be a significant risk factor in the development of
      breast abscess in lactating women in Zambia. Staphylococcus aureus remains the
      main causative agent, with MRSA accounting for 30.7% of isolates. SMX-TPM
      resistance likely stems from the wide spread use of the drug for PCP prophylaxis
      in HIV positive patients. It therefore should not be used for treatment of acute
      bacterial infections. HIV related breast infections could be considered as a
      possible entry point to HIV treatment now that the CD4 treatment guidelines have
      been adjusted to 350cells/cmm, although this requires further studies for
      validation.

PMID- 23170039
TI  - Performance of modified WHO presumptive criteria for diagnosis of HIV infection
      in children <18 months admitted to University Teaching Hospital in Lusaka.
AB  - BACKGROUND: Making a diagnosis of HIV infection in children aged less than 18
      months remains a challenge in low resource settings like Zambia due to the
      limited availability of gold standard testing with HIV DNA PCR. Clinicians in
      rural areas have to depend on clinical diagnosis to start HAART as they wait for
      the dry blood spot (DBS) for DNA PCR results sent from the urban centers. 
      METHODS: This descriptive cross-sectional study was performed at the University
      Teaching Hospital, Lusaka, Zambia. 299 HIV-exposed children aged less than 18
      months were enrolled following a consent procedure. Patients were evaluated for
      HIV infection based on the World Health Organization's presumptive diagnostic
      criteria (WHO-PDC), integrated management of childhood illnesses (IMCI) criteria,
      select physical exam abnormalities, and CD4% and findings were compared with HIV
      DNA PCR results.  RESULTS: Of the 299 exposed patients analyzed, 111(37%) were
      found to be HIV-positive by DNA PCR. The median CD4% in the infected children was
      18%. WHO-PDC used on its own had 23% sensitivity (95% CI 17-32%) and 93%
      specificity (88-96%), respectively, whereas IMCI criterion had 10% sensitivity (6
      17%) and 97% specificity (94-99%), respectively. Multivariate analysis was used
      to identify the most sensitive predictors when combined with the WHO-PDC and IMCI
      criterion. WHO-PDC with CD4% improved the sensitivity to 77% (68-83%) with a
      specificity of 83% (77-88%), positive predictive value (PPV) of 73% (64-80%) and
      negative predictive value (NPV) of 86% (80-90%). IMCI with CD4% improved
      sensitivity to 80% (71-87%) with a specificity of 88% (82-92%), PPV 78% (69-85%)
      and NPV 89% (84-93%). The addition of individual physical exam findings without
      CD4% improved the sensitivity of WHO-PDC only modestly. When the WHO-PDC,
      weight<3(rd) percentile, hepatomegaly, splenomegaly, lymphadenopathy and CD4%
      were combined, the sensitivity improved to 85% (77-90%), specificity 63% (56
      70%), PPV 58% (50-65%) and NPV of 88% (81-92%).  CONCLUSION: The WHO-PDC clinical
      algorithm can be improved when combined with a CD4% <25% in children less than 12
      months of age and CD4% <20% in those between 12 and 18 months.

PMID- 23170040
TI  - Tailored fibro-porous structure of electrospun polyurethane membranes, their size
      dependent properties and trans-membrane glucose diffusion.
AB  - The aim of this study was to develop polyurethane (PU) based fibro-porous
      membranes and to investigate the size-effect of hierarchical porous structure on
      permeability and surface properties of the developed electrospun membranes. Non
      woven SelectophoreTM PU membranes having tailored fibre diameters, pore sizes,
      and thickness were spun using electrospinning, and their chemical, physical and
      glucose permeability properties were characterised. Solvents, solution
      concentration, applied voltage, flow rate and distance to collector, each were
      systematically investigated, and electrospinning conditions for tailoring fibre
      diameters were identified. Membranes having average fibre diameters - 347, 738
      and 1102 nm were characterized, revealing average pore sizes of 800, 870 and 1060
      nm and pore volumes of 44, 63 and 68% respectively. Hydrophobicity increased with
      increasing fibre diameter and porosity. Effective diffusion coefficients for
      glucose transport across the electrospun membranes varied as a function of
      thickness and porosity, indicating high flux rates for mass transport.
      Electrospun PU membranes having significantly high pore volumes, extensively
      interconnected porosity and tailorable properties compared to conventional
      solvent cast membranes can find applications as coatings for sensors requiring
      analyte exchange.

PMID- 23170041
TI  - A Framework for the Comparison of Maximum Pseudo Likelihood and Maximum
      Likelihood Estimation of Exponential Family Random Graph Models.
AB  - The statistical modeling of social network data is difficult due to the complex
      dependence structure of the tie variables. Statistical exponential families of
      distributions provide a flexible way to model such dependence. They enable the
      statistical characteristics of the network to be encapsulated within an
      exponential family random graph (ERG) model. For a long time, however, likelihood
      based estimation was only feasible for ERG models assuming dyad independence. For
      more realistic and complex models inference has been based on the pseudo
      likelihood. Recent advances in computational methods have made likelihood-based
      inference practical, and comparison of the different estimators possible.In this
      paper, we present methodology to enable estimators of ERG model parameters to be
      compared. We use this methodology to compare the bias, standard errors, coverage
      rates and efficiency of maximum likelihood and maximum pseudo-likelihood
      estimators. We also propose an improved pseudo-likelihood estimation method aimed
      at reducing bias. The comparison is performed using simulated social network data
      based on two versions of an empirically realistic network model, the first
      representing Lazega's law firm data and the second a modified version with
      increased transitivity. The framework considers estimation of both the natural
      and the mean-value parameters.The results clearly show the superiority of the
      likelihood-based estimators over those based on pseudo-likelihood, with the bias
      reduced pseudo-likelihood out-performing the general pseudo-likelihood. The use
      of the mean value parameterization provides insight into the differences between
      the estimators and when these differences will matter in practice.

PMID- 23170042
TI  - Analysis of vanin-1 upregulation and lipid accumulation in hepatocytes in
      response to a high-fat diet and free fatty acids.
AB  - High-fat diet is one of the causes of nonalcoholic fatty liver disease. We have
      previously demonstrated that high-fat diet induces upregulation of adipose
      differentiation-related protein mRNA expression accompanied by lipid droplet
      formation in mouse liver. Vanin-1 is a ubiquitous epithelial ectoenzyme that has
      pantetheinase activity and produces cysteamine, a potent endogenous antioxidant.
      In the present study, we analyzed the expression of hepatic vanin-1 mRNA
      following the administration of a high-fat diet in mice as well as free fatty
      acids in hepatocyte cultures and speculated its possible mechanism. Vanin-1 mRNA
      levels in the livers of mice were upregulated within a day of the high-fat diet,
      even before the expression of adipose differentiation-related protein mRNA and
      lipid accumulation. An in vitro analysis using HuH-7 cells revealed a significant
      upregulation of vanin-1 mRNA by as low as 0.01 mM oleic acid; however, lipid
      accumulation in hepatocytes was not affected at this concentration. Furthermore,
      vanin-1 mRNA was differentially upregulated by various free fatty acids
      irrespective of the grade of lipid accumulation. These findings indicate that the
      upregulation of vanin-1 precedes lipid accumulation and is differentially
      mediated by various types of free fatty acids in the model, presenting vanin-1 as
      a novel player in the pathogenesis of nonalcoholic fatty liver disease.

PMID- 23170043
TI  - Identification of the radicals formed in the reactions of some endogenous
      photosensitizers with oleic acid under the UVA irradiation.
AB  - Electron spin resonance measurements were performed for the reactions of some
      endogenous photosensitizers (flavin mononucleotide or flavin adenine dinucleotide
      or folic acid or beta-nicotinamide adenine dinucleotide or beta-nicotinamide
      adenine dinucleotide phosphate or pyridoxal-5'-phosphate or urocanic acid) with
      oleic acid under the ultraviolet light A irradiation using alpha-(4-pyridyl-1
      oxide)-N-tert-butylnitrone as a spin trap reagent. Of the endogenous
      photosensitizers, prominent electron spin resonance signals (alpha(N) = 1.58 mT
      and alpha(H)beta = 0.26 mT) were observed for the reaction mixture of flavin
      mononucleotide (or flavin adenine dinucleotide or folic acid), suggesting that
      radical species form in the reaction mixtures. Singlet oxygen seems to
      participate in the formation of the radicals because the electron spin resonance
      peak heights increased for the reactions in D(2)O to a great extent. A high
      performance liquid chromatography-electron spin resonance-mass spectrometry was
      employed to identify the radicals formed in the reactions of the endogenous
      photosensitizers (flavin mononucleotide or flavin adenine dinucleotide or folic
      acid) with oleic acid under the ultraviolet light A irradiation. The high
      performance liquid chromatography-electron spin resonance-mass spectrometry
      analyses showed that 7-carboxyheptyl and 1-(3-carboxypropyl)-4-hydroxybutyl
      radicals form in the reaction mixture of flavin mononucleotide (or flavin adenine
      dinucleotide or folic acid).

PMID- 23170044
TI  - Zinc supplementation therapy improves the outcome of patients with chronic
      hepatitis C.
AB  - We administered zinc supplementation therapy over three years to patients with
      chronic hepatitis C and reported and that the aspartate aminotransferase (AST)
      and alanine aminotaransferase (ALT) levels decreased, and platelet counts
      increased, significantly in the group with increased serum zinc concentrations.
      We are continuing this treatment to clarify the long-term consequences and report
      here the changes in serum zinc concentrations over seven years and compare the
      cumulative incidence of hepatocellular carcinoma (HCC). We administered
      polaprezinc to 32 patients, randomly selected for zinc therapy (treatment group),
      while another 30 formed the control group. We measured the serum zinc and albumin
      concentrations and conducted a prospective study to determine long-term outcomes.
      The changes and rates of change of serum zinc concentrations after seven years
      were 76.7 +/- 18.2 ug/dl and +0.302 +/- 0.30% in the treatment group and 56.7 +/-
      12.4 ug/dl and +0.033 +/- 0.21% in the control group and had increased
      significantly (p = 0.0002, p = 0.0036). Progression of liver disease seemed to
      vary, depending on serum albumin concentrations. In the group with baseline serum
      albumin concentrations of 4.0 g/dl or more, the change and rate of change of
      serum zinc concentrations increased significantly, and the cumulative incidence
      of HCC tended to decrease, in the treated group. According to multivariate
      analysis, the factors that contribute to a reduction in the incidence of HCC are
      zinc therapy (risk ratio: 0.113, 95% CI: 0.015-0.870, p = 0.0362), and platelet
      counts (0.766, 0.594-0.989, 0.0409). Zinc supplementation therapy seems to
      improve liver pathology and reduce the incidence of HCC.

PMID- 23170045
TI  - Combination of proton pump inhibitor and rebamipide, a free radical scavenger,
      promotes artificial ulcer healing after endoscopic submucosal dissection with
      dissection size >40 mm.
AB  - In our previous study, the healing effect of proton pump inhibitor plus
      rebamipide for endoscopic submucosal dissection-related artificial ulcer smaller
      than 40 mm showed statistical significance. However, such effect of the
      combination was not yet clear for ulcers with dissected diameter more than 40 mm.
      The aim of this present study was to resolve this problem under sufficient
      statistical power, with adequate sample size. We conducted a randomized
      controlled study. Either the proton pump inhibitor mono-therapy or the
      combination therapy was prescribed for 28 days after endoscopic submucosal
      dissection. Eighty-seven patients were eligible for outcome evaluation.
      Combination therapy was significantly superior to mono-therapy, 27.8% vs 0%
      reached healing stage (scar stage) in cases with ulcers of dissection diameter
      more than 40 mm. In conclusion, the combination therapy with rebamipide was
      favorable regimen in patients with larger artificial ulcer after endoscopic
      submucosal dissection.

PMID- 23170046
TI  - Strategies for peptic ulcer healing after 1 week proton pump inhibitor-based
      triple Helicobacter pylori eradication therapy in Japanese patients: differences
      of gastric ulcers and duodenal ulcers.
AB  - Helicobacter pylori (H. pylori) eradication therapy alone is insufficient to
      ensure healing of large ulcers with H. pylori-positive gastric ulcer (GU). The
      question of what is the optimum antiulcer treatment following H. pylori
      eradication therapy has not been fully elucidated. Furthermore, the ulcer healing
      effects of eradication therapy itself with H. pylori-positive duodenal ulcer (DU)
      have not been investigated. In GU study, the eradication therapy + proton pump
      inhibitor (PPI) group (group A) were administered eradication therapy followed by
      7 weeks of a PPI, and the eradication therapy + gastroprotective drug (GP) group
      (group B) eradication therapy followed by 7 weeks of a GP. In DU study, the
      eradication therapy + PPI group (group C) were administered eradication therapy
      followed by 5 weeks of a PPI, and the eradication therapy only group (group D)
      was eradication therapy alone. In GU study, healing rates for ulcer of >=15 mm in
      diameter were significant greater in the group A. In DU study, high healing rates
      were seen both the group C and D. In conclusion, a PPI could significantly heal
      GU than a GP after eradication therapy in GU. Meanwhile, the eradication alone is
      sufficient for DU.

PMID- 23170047
TI  - Bisphosphonate-induced gastrointestinal mucosal injury is mediated by
      mitochondrial superoxide production and lipid peroxidation.
AB  - Bisphosphonates such as alendronate and risedronate are commonly used for the
      treatment of postmenopausal osteoporosis. They have the gastrointestinal adverse
      effects such as erosions and ulcers in stomach and small intestine. However, the
      detailed biological mechanism remains to be elucidated. Since alendronate is
      suggested to increase the risk of non-steroidal anti-inflammatory drug-related
      gastropathy, we hypothesized that bisphosphonates and non-steroidal anti
      inflammatory drugs have the same pathophysiological mechanisms in
      gastrointestinal mucosa: Bisphosphonates may induce cellular lipid peroxidation
      by inducing the production of mitochondrial superoxide. We also hypothesized that
      geranylgeranylacetone, an antiulcer drug, may prevent lipid peroxidation by
      reducing superoxide production. We treated gastric RGM1 cells and small
      intestinal IEC6 cells with alendronate or risedronate, and examined cellular
      injury, lipid peroxidation and superoxide production with specific fluorescent
      dyes, and underwent electron paramagnetic resonance spectroscopy to detect the
      production of superoxide in vitro. The results indicated that bisphosphonates
      indeed induced cellular injury, cellular lipid peroxidation, and superoxide
      production. We also demonstrated that the pretreatment of geranylgeranylacetone
      decreased superoxide production and prevented cellular lipid peroxidation. These
      results suggested that bisphosphonates, like non-steroidal anti-inflammatory
      drugs, induce lipid peroxidation by producing mitochondrial superoxide, which was
      prevented by geranylgeranylacetone.

PMID- 23170048
TI  - An immunosuppressive subtype of neutrophils identified in patients with
      hepatocellular carcinoma.
AB  - Functional disorders of various immune cells have been reported in hepatocellular
      carcinoma (HCC) patients. Recently, distinct subsets of neutrophils
      (polymorphonuclear leukocytes, PMN) have been identified in hosts with enhanced
      or impaired cell-mediated immunity. In this study, therefore, plasma factors and
      PMN from HCC patients were immunobiologically investigated. Plasma neopterin and
      CCL17 levels were measured by ELISA in 95 HCC patients. Peripheral PMN were
      isolated from each HCC patient and tested for CCL2 or CCL3 production by ELISA
      and flow cytometry. The results showed elevated plasma neopterin levels in HCC
      patients, while CCL17 levels decreased in correlation with tumor size. PMN from
      HCC patients produced CCL2, while PMN from healthy subjects did not. Moreover,
      CCL2 production by PMN was significantly increased in proportion to tumor load.
      When HCC patients were divided into two groups based on CCL2 produced by PMN, the
      survival rate of the CCL2 high group was significantly lower than that for other
      patients. While CCL3 production by PMN was also significantly increased in HCC
      patients, their CCL3 production did not correlate with tumor load and survival.
      The CCL2/CCL3 ratio in culture fluids of each PMN was also increased in
      proportion to tumor size. These results suggest that cell-mediated immunity may
      be impaired in advanced HCC patients. Moreover, distinct PMN subsets may exist in
      the peripheral blood of HCC patients. These PMN subsets, especially CCL2
      producing PMN, may be involved in tumor extension and the survival outcomes for
      HCC patients.

PMID- 23170049
TI  - A secure "double-check" technique of bedside post pyloric feeding tube placement
      using transnasal endoscopy.
AB  - Enteral feeding has become an important means of providing nutritional support to
      seriously ill patients. Placement of the feeding tube through the pyloric ring
      and past the ligament of Treitz into the proximal jejunum is critical to reduce
      the risk of gastroesophageal regurgitation and microaspiration. We started
      utilizing transnasal endoscopy for intestinal feeding tube placement, placing
      enteral tubes for 40 patients between March 2008 and February 2009. Although we
      achieved a high success rate comparable to previous reports, we experienced
      several cases of failure, which was corrected with repeated endoscopy. Based on
      these experiences, we modified our method by adding a "double-check" transnasal
      endoscopy through the other nasal passage. After April 2010, we have placed the
      feeding tube by "double-check" method for all patients (more than 40 patients)
      who required transnasal endoscopic feeding tube placement. We have not
      experienced any misplacement in all these patients after 24 h later with 100%
      successful rate since the introduction of "double-check" procedure. We describe
      our experience with "double-check" transnasal endoscopic feeding tube placement,
      which we found to be a helpful adjunct, for patients in intensive care unit.

PMID- 23170050
TI  - Efficacy of rebamipide for low-dose aspirin-related gastrointestinal symptoms.
AB  - Gastrointestinal symptoms are a problematic issue for patients who take low-dose
      aspirin for long time. We conducted a pilot study to investigate the efficacy of
      combination therapy with proton pump inhibitor and rebamipide. This was a
      prospective, randomized, double-blind, placebo-controlled cross-over study. All
      the subjects received aspirin 100 mg and omeprazole 20 mg. The subjects were
      divided into two groups and received either rebamipide 300 mg or placebo, which
      was prescribed for 4 weeks. The subjects were instructed to record their
      gastrointestinal symptom rating scale before the study and 1 and 4 weeks after
      beginning the protocol. These scores of the groups were compared before and after
      the treatment to evaluate the severity of their symptoms and the number of
      symptom items present in each group. For the subjects receiving rebamipide, the
      total prevalence of lower gastrointestinal symptoms was significantly different
      from the placebo group (p=0.0093) at week 4. No troublesome symptoms were
      observed in the rebamipide group. Inconclusion, the administration of rebamipide
      prevented the occurrence of troublesome symptoms, especially lower
      gastrointestinal symptoms, in patients taking aspirin and omeprazole. Rebamipide
      is a candidate drug for combination therapy with proton pump inhibitors to
      prevent low-dose aspirin-induced gastrointestinal symptoms.

PMID- 23170051
TI  - Distinct affinity of nuclear proteins to the surface of chrysotile and
      crocidolite.
AB  - The inhalation of asbestos is a risk factor for the development of malignant
      mesothelioma and lung cancer. Based on the broad surface area of asbestos fibers
      and their ability to enter the cytoplasm and nuclei of cells, it was hypothesized
      that proteins that adsorb onto the fiber surface play a role in the cytotoxicity
      and carcinogenesis of asbestos fibers. However, little is known about which
      proteins adsorb onto asbestos. Previously, we systematically identified asbestos
      interacting proteins and classified them into eight sub-categories:
      chromatin/nucleotide/RNA-binding proteins, ribosomal proteins, cytoprotective
      proteins, cytoskeleton-associated proteins, histones and hemoglobin. Here, we
      report an adsorption profile of proteins for the three commercially used asbestos
      compounds: chrysotile, crocidolite and amosite. We quantified the amounts of
      adsorbed proteins by analyzing the silver-stained gels of sodium dodecyl sulfate
      polyacrylamide gel electrophoresis with ImageJ software, using the bands for
      amosite as a standard. We found that histones were most adsorptive to crocidolite
      and that chromatin-binding proteins were most adsorptive to chrysotile. The
      results suggest that chrysotile and crocidolite directly interact with chromatin
      structure through different mechanisms. Furthermore, RNA-binding proteins
      preferably interacted with chrysotile, suggesting that chrysotile may interfere
      with transcription and translation. Our results provide novel evidence
      demonstrating that the specific molecular interactions leading to carcinogenesis
      are different between chrysotile and crocidolite.

PMID- 23170052
TI  - Anti-oxidative and anti-inflammatory effects of spirulina on rat model of non
      alcoholic steatohepatitis.
AB  - The pathogenesis of nonalcoholic steatohepatitis (NASH) remains unclear, but
      accumulating data suggest oxidative stress and the relationship between
      inflammation and immunity plays a crucial role. The aim of this study is to
      investigate the spirulina, which is a blue-green algae rich in proteins and other
      nutritional elements, and its component-phycocyanin effect on a rat model of
      NASH. NASH model rats were established by feeding male Wistar rats with choline
      deficient high-fat diet (CDHF) and intermittent hypoxemia by sodium nitrite
      challenge after 5 weeks of CDHF. After experimental period of 10 weeks, blood and
      liver were collected to determine oxidative stress injuries and efficacies of
      spirulina or phycocyanin on NASH model rats. In the NASH model rats, increase in
      plasma liver enzymes and liver fibrosis, increases in productions of reactive
      oxygen species from liver mitochondria and from leukocytes, the activation of
      nuclear factor-kappa B, and the change in the lymphocyte surface antigen ratio
      (CD4(+)/CD8(+)) were observed. The spirulina and phycocyanin administration
      significantly abated these changes. The spirulina or phycocyanin administration
      to model rats of NASH might lessen the inflammatory response through anti
      oxidative and anti-inflammatory mechanisms, breaking the crosstalk between
      oxidative stress and inflammation, and effectively inhibit NASH progression.

PMID- 23170053
TI  - Comparative effects of doenjang prepared from soybean and brown rice on the body
      weight and lipid metabolism in high fat-fed mice.
AB  - The comparative effects of doenjang prepared from fermented soybean or brown rice
      on the body weight and lipid metabolism in C57BL/6N mice fed with high fat diet
      were investigated. The animals were randomly divided and given experimental diets
      for eight weeks: normal control diet, high fat diet, and high fat diet
      supplemented with soybean doenjang, brown rice doenjang, brown rice-rice bran
      doenjang, or brown rice-red ginseng marc doenjang. At the end of the experimental
      period, the HF group exhibited a marked increase in body weight, body fat, plasma
      triglyceride concentration, and atherogenic index relative to the normal control
      diet group. However, diet supplementation of doenjang counteracted this high fat
      induced hyperlipidemia through modulation of lipogenesis and adipokine
      production. In general, compared with soybean doenjang, the brown rice-rice bran
      doenjang and brown rice-red ginseng marc doenjang were similarly effective in
      improving the lipid metabolism under high fat diet condition. These findings
      demonstrate that brown rice, in combination with rice bran or red ginseng marc,
      may be useful as a functional biomaterial for the preparation of doenjang with
      strong anti-obesity effect and hypolipidemic action.

PMID- 23170054
TI  - Fish oil at low dietary levels enhances physiological activity of sesamin to
      increase hepatic fatty acid oxidation in rats.
AB  - We previously demonstrated that a diet containing fish oil at a level of 80 g/kg
      strongly stimulated the physiological activity of a sesame sesamin preparation
      containing sesamin and episesamin at equal amounts to increase hepatic fatty acid
      oxidation. This study was conducted to clarify whether fish oil at lower dietary
      levels enhances the physiological activity of sesamin to increase hepatic fatty
      acid oxidation. Rats were fed experimental diets supplemented with 0 or 2 g
      sesamin/kg, and containing 0, 15 or 30 g fish oil/kg for 15 days. Among rats fed
      sesamin-free diets, diets containing 15 and 30 g fish oil/kg slightly increased
      the activity of enzymes involved in hepatic fatty acid oxidation. Sesamin
      increased these values irrespective of the presence or absence of fish oil in
      diets; however, the extent of the increase of many parameters was much greater in
      rats given fish oil-containing diets than in those fed a fish oil-free diet.
      Diets simultaneously containing sesamin and fish oil increased the gene
      expression of various peroxisomal fatty acid oxidation enzymes in a synergistic
      manner; but they were ineffective in causing a synergistic increase in mRNA
      levels of mitochondrial fatty acid oxidation enzymes. The extent of the
      synergistic increase in the activity of hepatic fatty acid oxidation enzymes and
      mRNA levels of the peroxisomal enzymes was indistinguishable between diets
      containing 15 and 30 g fish oil/kg and appeared comparable to that observed
      previously with a diet containing 80 g fish oil/kg.

PMID- 23170055
TI  - Application of LC-MS/MS analysis of plasma amino acids profiles in children with
      autism.

PMID- 23170057
TI  - Association of markers at chromosome 15q14 in Chinese patients with moderate to
      high myopia.
AB  - PURPOSE: To investigate the association of two reported regions on chromosome 15
      with moderate to high myopia in two Chinese cohorts from southern China. METHODS:
      Two candidate regions on 15q14 and 15q25 were selected based on reported
      association with refractive error in the literature. Five single nucleotide
      polymorphisms (SNPs) were genotyped in 300 university students with high myopia
      at Guangzhou and 308 without refractive error, and 96 university students of
      Chaoshan Chinese origin with moderate to high myopia and 96 without refractive
      error. Genotypes were evaluated using direct sequencing and analyzed with chi
      square, Armitage trend, and Mantel-Haenszel tests, and regression analysis.
      RESULTS: Of the five SNPs screened, alleles of rs634990 and rs524952 in the 15q14
      region showed evidence of allelic association with moderate to high myopia
      (p<8.81*10(-7) and p<1.57*10(-6), respectively) in the Guangzhou group, but not
      in the Chaoshan group. The SNPs at 15q25 did not show significant association in
      any group. Association of rs634990 and rs524952 were still significant when both
      groups were combined into a single analysis (p<1.66*10(-6) and p<2.72*10(-6),
      respectively), and for genotypic, additive, and dominant models. CONCLUSIONS:
      This study confirms the significant association of rs634990 and rs524952 on
      chromosome 15q14 previously reported in European and Japanese populations with
      high myopia in the Guangzhou but not the Chaoshan Chinese populations, suggesting
      that genetic contributors to high myopia in the Chaoshan population might be
      different from other Chinese populations.

PMID- 23170058
TI  - Induction of amyloid-beta(1-42) in the retina and optic nerve head of chronic
      ocular hypertensive monkeys.
AB  - PURPOSE: Recent studies have indicated that accumulation of amyloid beta(1-42)
      (Abeta(1-42)), which is associated with the progression of Alzheimer disease, may
      also be responsible for retinal ganglion cell death in glaucoma. The purpose of
      this study was to investigate the expression and localization of Abeta(1-42) in
      the retina and the optic nerve head (ONH) of monkeys with experimental glaucoma.
      METHODS: Five cynomolgus monkeys with a glaucomatous left eye at 4, 9, 11, 15,
      and 24 weeks after laser photocoagulation treatment were studied by
      immunohistochemical methods. Another two cynomolgus monkeys with a glaucomatous
      left eye at 133 weeks after laser photocoagulation treatment were used to measure
      Abeta(1-42) concentrations in the retina by enzyme-linked immunosorbent assay.
      RESULTS: At 11 to 24 weeks after the laser photocoagulation treatment, Abeta(1
      42) was upregulated in the nerve fiber layer (NFL) and the ganglion cell layer
      (GCL) of the retina and the ONH, but the expression of amyloid precursor protein
      decreased in the NFL and ONH from levels at 9 weeks. The localizations of Abeta(1
      42) were merged in glial fibrillary acidic protein-positive astroglial cells but
      not phosphorylated neurofilament heavy- or nonphosphorylated neurofilament heavy
      positive axons in the retina and the ONH. Likewise, Abeta(1-42) concentrations in
      the retina of monkeys increased in the chronic stage of glaucoma. CONCLUSIONS:
      These findings indicate that the upregulation of Abeta(1-42) after an intraocular
      pressure elevation could apply to monkeys since the structure of the ONH is more
      similar to humans than that of rodents.

PMID- 23170059
TI  - Adult mice transplanted with embryonic retinal progenitor cells: new approach for
      repairing damaged optic nerves.
AB  - PURPOSE: Retinal ganglion cell (RGC) death and optic nerve degeneration are
      complex processes whose underlying molecular mechanisms are only vaguely
      understood. Treatments commonly used for optic nerve degeneration have little
      long-term value and only prolong degeneration. Recent advances in stem cell
      replacement therapy offer new ways to overcome RGC loss by transferring healthy
      cells into eyes of afflicted individuals. However, studies on stem cell
      replacement for optic nerve degeneration are hampered by limitations of the
      available animal models, especially genetic models. We have developed a mouse
      model in which RGCs are genetically ablated in adult mice with subsequent
      degeneration of the optic nerve. In the study reported here, we used this model
      to determine whether embryonic retinal progenitor cells (RPCs) removed from donor
      retinas when RPCs are committing to an RGC fate could restore lost RGCs. METHODS:
      We used the RGC-depleted model as a host for transplanting donor green
      fluorescent protein (GFP)-labeled RPCs from embryonic retinas that are maximally
      expressing Atoh7, a basic helix-loop-helix gene essential for RGC specification.
      Dissociated GFP-labeled RPCs were characterized in situ by immunolabeling with
      antibodies against proteins known to be expressed in RPCs at embryonic day
      (E)14.5. Dissociated retinal cells were injected into the vitreous of one eye of
      RGC-depleted mice at two to six months of age. The injected and non-injected
      retinas were analyzed for gene expression using immunolabeling, and the
      morphology of optic nerves was assessed visually and with histological staining
      at different times up to four months after injection. RESULTS: We demonstrate the
      successful transfer of embryonic GFP-labeled RPCs into the eyes of RGC-depleted
      mice. Many transplanted RPCs invaded the ganglion cell layer, but the efficiency
      of the invasion was low. GFP-labeled cells within the ganglion cell layer
      expressed genes associated with early and late stages of RGC differentiation,
      including Pou4f1, Pou4f2, NFL, Map2, and syntaxin. Several GFP-labeled cells were
      detected within the injected optic nerves of RGC-depleted mice, and in most
      cases, we observed a significant increase in the thickness of the RPC-injected
      optic nerves compared with non-injected controls. We also observed more bundled
      axons emanating from RPC-injected retinas compared with RGC-depleted controls.
      CONCLUSIONS: The results offer a new approach for regenerating damaged optic
      nerves and indicate that a significant number of E14.5 RPCs are able to
      differentiate into RGCs in the foreign environment of the adult retina. However,
      the proportion of RPCs that populated the ganglion cell layer and contributed to
      the optic nerve was not sufficient to account for the increased thickness and
      higher number of axons. The results support the hypothesis that the injected
      E14.5 RPCs are contributing autonomously and non-autonomously to restoring
      damaged optic nerves.

PMID- 23170061
TI  - Clinical characterization and mitochondrial DNA sequence variations in Leber
      hereditary optic neuropathy.
AB  - PURPOSE: Leber hereditary optic neuropathy (LHON), a maternally inherited
      disorder, results from point mutations in mitochondrial DNA (mtDNA). MtDNA is
      highly polymorphic in nature with very high mutation rate, 10-17 fold higher as
      compared to nuclear genome. Identification of new mtDNA sequence variations is
      necessary to establish a clean link with human disease. Thus this study was aimed
      to assess or evaluate LHON patients for novel mtDNA sequence variations.
      MATERIALS AND METHODS: Twenty LHON patients were selected from the neuro
      ophthalmology clinic of the All India Institute of Medical Sciences, New Delhi,
      India. DNA was isolated from whole blood samples. The entire coding region of the
      mitochondrial genome was amplified by PCR in 20 patients and 20 controls. For
      structural analysis (molecular modeling and simulation) the MODELER 9.2 program
      in Discovery Studio (DS 2.0) was used. RESULTS: MtDNA sequencing revealed a total
      of 47 nucleotide variations in the 20 LHON patients and 29 variations in 20
      controls. Of 47 changes in patients 21.2% (10/47) were nonsynonymous and the
      remaining 78.72% (37/47) were synonymous. Five nonsynonymous changes, including
      primary LHON mutations (NADH dehydrogenase subunit 1 [ND1]:p.A52T, NADH
      dehydrogenase subunit 6 [ND6]:p.M64V, adenosine triphosphate [ATP] synthase
      subunit a (F-ATPase protein 6) [ATPase6]:p.M181T, NADH dehydrogenase subunit 4
      [ND4]:p.R340H, and cytochrome B [CYB]:p.F181L), were found to be pathogenic. A
      greater number of changes were present in complex I (53.19%; 25/47), followed by
      complex III (19.14%; 9/47), then complex IV (19.14%; 9/47), then complex V (8.5%;
      4/47). Nonsynonymous variations may impair respiratory chain and oxidative
      phosphorylation (OXPHOS) pathways, which results in low ATP production and
      elevated reactive oxygen species (ROS) levels. Oxidative stress is the underlying
      etiology in various diseases and also plays a crucial role in LHON. CONCLUSIONS:
      This study describes the role of mtDNA sequence variations in LHON patients.
      Primary LHON mutations of mtDNA are main variants leading to LHON, but mutations
      in other mitochondrial genes may also play an important role in pathogenesis of
      LHON as indicated in the present study. Certain alleles in certain haplogroups
      have protective or deleterious roles and hence there is a need to analyze a large
      number of cases for correlating phenotype and disease severity with mutation and
      mtDNA haplogroups.

PMID- 23170060
TI  - Review: taurine: a "very essential" amino acid.
AB  - Taurine is an organic osmolyte involved in cell volume regulation, and provides a
      substrate for the formation of bile salts. It plays a role in the modulation of
      intracellular free calcium concentration, and although it is one of the few amino
      acids not incorporated into proteins, taurine is one of the most abundant amino
      acids in the brain, retina, muscle tissue, and organs throughout the body.
      Taurine serves a wide variety of functions in the central nervous system, from
      development to cytoprotection, and taurine deficiency is associated with
      cardiomyopathy, renal dysfunction, developmental abnormalities, and severe damage
      to retinal neurons. All ocular tissues contain taurine, and quantitative analysis
      of ocular tissue extracts of the rat eye revealed that taurine was the most
      abundant amino acid in the retina, vitreous, lens, cornea, iris, and ciliary
      body. In the retina, taurine is critical for photoreceptor development and acts
      as a cytoprotectant against stress-related neuronal damage and other pathological
      conditions. Despite its many functional properties, however, the cellular and
      biochemical mechanisms mediating the actions of taurine are not fully known.
      Nevertheless, considering its broad distribution, its many cytoprotective
      attributes, and its functional significance in cell development, nutrition, and
      survival, taurine is undoubtedly one of the most essential substances in the
      body. Interestingly, taurine satisfies many of the criteria considered essential
      for inclusion in the inventory of neurotransmitters, but evidence of a taurine
      specific receptor has yet to be identified in the vertebrate nervous system. In
      this report, we present a broad overview of the functional properties of taurine,
      some of the consequences of taurine deficiency, and the results of studies in
      animal models suggesting that taurine may play a therapeutic role in the
      management of epilepsy and diabetes.

PMID- 23170063
TI  - Phylogenetic analysis and comparative genomics of purine riboswitch distribution
      in prokaryotes.
AB  - Riboswitches are regulatory RNA that control gene expression by undergoing
      conformational changes on ligand binding. Using phylogenetic analysis and
      comparative genomics we have been able to identify the class of genes/operons
      regulated by the purine riboswitch and obtain a high-resolution map of purine
      riboswitch distribution across all bacterial groups. In the process, we are able
      to explain the absence of purine riboswitches upstream to specific genes in
      certain genomes. We also identify the point of origin of various purine
      riboswitches and argue that not all purine riboswitches are of primordial origin,
      and that some purine riboswitches must have originated after the divergence of
      certain Firmicute orders in the course of evolution. Our study also reveals the
      role of horizontal transfer events in accounting for the presence of purine
      riboswitches in some gammaproteobacterial species. Our work provides significant
      insights into the origin, distribution and regulatory role of purine riboswitches
      in prokaryotes.

PMID- 23170062
TI  - Review: tauopathy in the retina and optic nerve: does it shadow pathological
      changes in the brain?
AB  - Tau protein's versatility lies in its functions within the central nervous
      system, including protein scaffolding and intracellular signaling. Tauopathy has
      been one of the most extensively studied neuropathologies among the
      neurodegenerative diseases. Because the retina and optic nerve are parts of the
      central nervous system, we hypothesize that tauopathy also plays a role in
      various eye diseases. However, little is known about tauopathy in the retina and
      optic nerve. Here, we summarize the findings from histopathological studies on
      animal models and human specimens with distinct neurodegenerative diseases.
      Similar pathological changes of tau protein can be found in Alzheimer's disease,
      frontotemporal lobe dementia, and glaucoma. In view of the important roles of
      tauopathy in the brain, it is hoped that this review can stimulate research on
      eye diseases of the retina and optic nerve.

PMID- 23170064
TI  - Newton, laplace, and the epistemology of systems biology.
AB  - For science, theoretical or applied, to significantly advance, researchers must
      use the most appropriate mathematical methods. A century and a half elapsed
      between Newton's development of the calculus and Laplace's development of
      celestial mechanics. One cannot imagine the latter without the former. Today,
      more than three-quarters of a century has elapsed since the birth of stochastic
      systems theory. This article provides a perspective on the utilization of systems
      theory as the proper vehicle for the development of systems biology and its
      application to complex regulatory diseases such as cancer.

PMID- 23170065
TI  - Associations of circulating inflammatory biomarkers with risk factors for
      colorectal cancer in colorectal adenoma patients.
AB  - Obesity and central adiposity are associated with colorectal cancer risk and have
      been linked to inflammation. Inflammation is a complex, interactive response that
      may most accurately be summarized through multiple, simultaneously measured
      cytokines. In this cross-sectional analysis, we investigated associations of
      circulating plasma levels of C-reactive protein (CRP), tumor necrosis factor
      alpha (TNF-alpha), interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-1beta
      (IL-1beta), and a combined inflammation z score with risk factors for colorectal
      cancer in colorectal adenoma patients (n = 92). Multivariable logistic regression
      was used to investigate associations between cytokine levels and known risk
      factors for colorectal neoplasms. Mean cytokine levels tended to increase with
      increasing body mass index (BMI), with statistically significant trends in
      relation to CRP, IL-6, and the combined inflammation z score (P for trend <
      0.001, 0.02, and <0.001, respectively). The odds ratios for associations of the
      inflammation z score with being overweight (BMI 25-29.9 kg/m(2)), obese (BMI >=
      30 kg/m(2)), or having a high waist-to-hip ratio were 4.33 (95% CI [confidence
      interval], 1.04-18.00), 5.54 (95% CI, 1.37-22.42), and 4.09 (95% CI, 1.67-9.98),
      respectively. Our findings support (1) associations of inflammation with
      increased general and central adiposity and (2) investigation of a combined
      inflammation score as a risk factor for colorectal neoplasms.

PMID- 23170066
TI  - All might have won, but not all have the prize: optimal treatment for substance
      abuse among adolescents with conduct problems.
AB  - Considerable evidence from the literature on treatment outcomes indicates that
      substance abuse treatment among adolescents with conduct problems varies widely.
      Treatments commonly used among this population are cognitive-behavioral therapy
      (CBT), 12-step facilitation, multisystemic therapy (MST), psychoeducation (PE),
      and motivational interviewing (MI). This manuscript thoroughly and systematically
      reviews the available literature to determine which treatment is optimal for
      substance-abusing adolescents with conduct problems. Results suggest that
      although there are several evidence-based and empirically supported treatments,
      those that incorporate family-based intervention consistently provide the most
      positive treatment outcomes. In particular, this review further reveals that
      although many interventions have gained empirical support over the years, only
      one holds the prize as being the optimal treatment of choice for substance abuse
      treatment among adolescents with conduct problems.

PMID- 23170067
TI  - What's In a Note: Construction of a Suicide Note Corpus.
AB  - This paper reports on the results of an initiative to create and annotate a
      corpus of suicide notes that can be used for machine learning. Ultimately, the
      corpus included 1,278 notes that were written by someone who died by suicide.
      Each note was reviewed by at least three annotators who mapped words or sentences
      to a schema of emotions. This corpus has already been used for extensive
      scientific research.

PMID- 23170069
TI  - Mimulus peregrinus (Phrymaceae): A new British allopolyploid species.
AB  - Polyploidization plays an important role in species formation as chromosome
      doubling results in strong reproductive isolation between derivative and parental
      taxa. In this note I describe a new species, Mimulus peregrinus (Phrymaceae),
      which represents the first recorded instance of a new British polyploid species
      of Mimulus (2n = 6x = 92) that has arisen since the introduction of this genus
      into the United Kingdom in the 1800's. Mimulus peregrinus presents floral and
      vegetative characteristics intermediate between Mimulus guttatus and Mimulus
      luteus, but can be distinguished from all naturalized British Mimulus species and
      hybrids based on a combination of reproductive and vegetative traits. Mimulus
      peregrinus displays high pollen and seed fertility as well as traits usually
      associated with genome doubling such as increased pollen and stomata size. The
      intermediate characteristics of Mimulus peregrinus between Mimulus guttatus (2n =
      2x = 28)and Mimulus luteus (2n = 4x = 60-62), and its close affinity with the
      highly sterile, triploid (2n = 3x = 44-45) hybrid taxon Mimulus * robertsii
      (Mimulus guttatus * Mimulus luteus), suggests that Mimulus peregrinus
      mayconstitute an example of recent allopolyploid speciation.

PMID- 23170068
TI  - Clinical management of localized colon cancer with capecitabine.
AB  - Large randomized trials demonstrated a benefit of adjuvant chemotherapy after
      resection of the primary colon cancer. It improves overall survival and reduces
      the risk of death, by 5% in UICC (Union Internationale Contre le Cancer) stage II
      and approximately 15%-20% in stage III. Fluoropyrimidines have been the standard
      drugs for the treatment of colon cancer since large randomized controlled trials
      demonstrated their efficacy and safety in treating patients suffering from this
      disease. Capecitabine is an orally administered fluoropyrimidine, which is
      preferably activated in tumor tissue to the active moiety 5-fluorouracil (5FU)
      and is cytotoxic through inhibition of DNA synthesis. It has proven equivalent
      efficacy and tolerability despite a changed toxicity profile compared to 5FU with
      less myelosuppression but more hand-and-foot syndrome. Capecitabine is well
      tolerated in elderly patients. The oral route of administration avoids frequent
      clinical visits as well as insertion of central venous catheters. The impact of
      the particular drug features on daily clinical practice is discussed in this
      review.

PMID- 23170070
TI  - Aristolochia vallisicola (Aristolochiaceae), a new species from Peninsular
      Malaysia.
AB  - A new species in the genus Aristolochia (Aristolochiaceae), Aristolochia
      vallisicola T.L.Yao, from Peninsular Malaysia is described and illustrated. Among
      all Peninsular Malaysian Aristolochia,itis the only species with a pinnately
      veined lamina and a disc-liked perianth limb. A distribution map is provided and
      its conservation status is assessed as Least Concern.

PMID- 23170071
TI  - Cuatrecasanthus (Vernonieae, Compositae): A revision of a north-central Andean
      genus.
AB  - Cuatrecasanthus is native to Ecuador and Peru and although several unusual
      characters define the genus, such as single flowered heads and corolla throat
      (limb) divided to the base with lobes that are thickened at the margins, the
      members of the genus were not recognized as especially closely related until
      relatively recently. All six species are described, including two new to science
      (Cuatrecasanthus kingii H. Rob. & V.A. Funk, sp. nov. and Cuatrecasanthus
      lanceolatus H. Rob. & V.A. Funk, sp. nov.), and one new combination is recognized
      (Cuatrecasanthus giannasii (Stutts) H. Rob. & V.A. Funk, comb. nov.). A key is
      provided along with images of the types, SEM photographs of the leaf surfaces, a
      distribution map, and illustrations of the two new species. All species are given
      a preliminary conservation status of Data Deficient in regard to the IUCN Red
      List of Threatened Species.

PMID- 23170072
TI  - Phylogenetic analyses place the Australian monotypic Revwattsia in Dryopteris
      (Dryopteridaceae).
AB  - Revwattsia fragilis (Watts) D.L. Jones (Dryopteridaceae), originally described as
      a Polystichum Roth by the pioneer Australian botanist Reverend W.W. Watts in
      1914, is a rare epiphytic fern endemic to northeastern Queensland, Australia.
      Known from only a few populations, it is restricted to tropical rainforests in
      the Atherton Tablelands. We used the cpDNA markers psbA-trnH, rbcL, rbcL-accD,
      rps4-trnS, trnG-trnR, trnL-trnF, and trnP-petG to infer the relationships of
      Revwattsia fragilis within Dryopteridaceae. Based on our molecular analysis, we
      were able to reject Watts's 1914 hypothesis of a close relationship to
      Polystichum. Its closest allies are a suite of Asian Dryopteris Adans. species
      including Dryopteris labordei, Dryopteris gymnosora, Dryopteris erythrosora and
      Dryopteris cystolepidota; maintaining Revwattsia renders Dryopteris paraphyletic.
      The epiphytic habit and distinctive long-creeping rhizome of Revwattsia appear to
      be autapomorphies and do not warrant its generic status. In the course of our
      investigation we confirmed that polyphyly of Dryopteris is also sustained by the
      inclusion of Acrorumohra (H.Ito) H.Ito, Acrophorus C.Presl, Arachniodes Blume,
      Diacalpe Blume, Dryopsis Holttum & P.J.Edwards, and Peranema D.Don. The epithet
      fragilis is occupied in Dryopteris, therefore we provide the name Dryopteris
      wattsiinom. nov. to accommodate Revwattsia fragilis in Dryopteris.

PMID- 23170073
TI  - First instalment in resolution of the Banksia spinulosa complex (Proteaceae): B.
      neoanglica, a new species supported by phenetic analysis, ecology and geography.
AB  - Taxa in the Banksia spinulosa Sm. complex (Proteaceae) have populations with
      sympatric, parapatric and allopatric distributions and unclear or disputed
      boundaries. Our hypothesis is that under biological, phenetic and diagnosable
      species concepts that each of the currently named taxa within the Banksia
      spinulosa complex is a separate species. Based on specimens collected as part of
      this study, and data recorded from specimens in six Australian herbaria,
      complemented by phenetic analysis (semi-strong multidimensional scaling and UPGMA
      clustering) and a detailed morphological study, we investigated both
      morphological variation and geographic distribution in the Banksia spinulosa
      complex. All specimens used for this study are held at the N.C.W. Beadle
      Herbarium or the National Herbarium of New South Wales. In total 23 morphological
      characters (11 quantitative, five binary, and seven multistate characters) were
      analysed phenetically for 89 specimens. Ordination and cluster analysis resulted
      in individuals grouping strongly allowing recognition of distinct groups
      consistent with their recognition as separate species. Additional morphological
      analysis was completed on all specimens using leaf, floral, fruit and stem
      morphology, providing clear cut diagnosable groups and strong support for the
      recognition of Banksia spinulosa var. cunninghamii and Banksia spinulosa var.
      neoanglica as species.

PMID- 23170074
TI  - Structural analysis of a heteropolysaccharide from Saccharina japonica by
      electrospray mass spectrometry in tandem with collision-induced dissociation
      tandem mass spectrometry (ESI-CID-MS/MS).
AB  - A fucoidan extracted from Saccharina japonica was fractionated by anion exchange
      chromatography. The most complex fraction F0.5 was degraded by dilute sulphuric
      acid and then separated by use of an activated carbon column. Fraction Y1 was
      fractionated by anion exchange and gel filtration chromatography while Fraction
      Y2 was fractionated by gel filtration chromatography. The fractions were
      determined by ESI-MS and analyzed by ESI-CID-MS/MS. It was concluded that F0.5
      had a backbone of alternating 4-linked GlcA and 2-linked Man with the first Man
      residue from the nonreducing end accidentally sulfated at C6. In addition, F0.5
      had a 3-linked glucuronan, in accordance with a previous report by NMR. Some
      other structural characteristics included GlcA 1->3 Man 1->4 GlcA, Man 1->3 GlcA
      1->4 GlcA, Fuc 1->4 GlcA and Fuc 1->3 Fuc. Finally, it was shown that fucose was
      sulfated at C2 or C4 while galactose was sulfated at C2, C4 or C6.

PMID- 23170075
TI  - Sepia ink oligopeptide induces apoptosis in prostate cancer cell lines via
      caspase-3 activation and elevation of Bax/Bcl-2 ratio.
AB  - Sepia ink oligopeptide (SIO) is a tripeptide extracted from Sepia ink. To test
      the hypothesis that SIO inhibits prostate cancer by inducing apoptosis, the
      effects of SIO on the proliferation of three human prostate cancer cell lines
      were examined using a CCK-8 assay. SIO significantly inhibited the proliferation
      of DU-145, PC-3 and LNCaP cells in a time- and dose-dependent manner. Flow
      cytometry studies showed that exposing DU-145, PC-3 and LNCaP cells to 5, 10, or
      15 mg/mL SIO for 24 h increased the percentage of the early-stage apoptotic cells
      from 11.84% to 38.26% (DU-145), 22.76% to 39.96% (PC-3) and 5.05% to 16.11%
      (LNCaP), respectively. In addition, typical morphologic changes were observed in
      the cells with acridine orange/ethidium bromide staining. SIO treatment induced
      strong S and G2/M phase cell cycle arrest in a dose-dependent manner in DU-145
      and LNCaP. In contrast, SIO treatment induced strong Sub G1 and G0/G1 phase cell
      cycle arrest in a dose-dependent manner in PC-3. SIO exposure for 24 h decreased
      the expression of the anti-apoptotic protein Bcl-2 and increased the expression
      of the apoptogenic protein Bax. Moreover, the Bax/Bcl-2expression ratio was
      increased. Concurrently, the expression of caspase-3 was upregulated. These data
      support our hypothesis that SIO has anticarcinogenic properties.

PMID- 23170076
TI  - Sarcophine-diol inhibits expression of COX-2, inhibits activity of cPLA2,
      enhances degradation of PLA2 and PLC(gamma)1 and inhibits cell membrane
      permeability in mouse melanoma B16F10 cells.
AB  - Sarcophine-diol (SD) is a semi-synthetic derivative of sarcophine with a
      significant chemopreventive effect against non-melanoma skin cancer both in vitro
      and in vivo. Recently, we have studied the effect of SD on melanoma development
      using the mouse melanoma B16F10 cell line. In this study, our findings show that
      SD suppresses cell multiplication and diminishes membrane permeability for
      ethidium bromide (EB), a model marker used to measure cell permeability for Ca2+
      ions. SD also decreases protein levels of COX-2, and increases degradation of
      phospholipases PLA2 and PLC(gamma)1 and diminishes enzymatic activity of the Ca2+
      dependent cPLA2. This lower membrane permeability for Ca2+-ions, associated with
      SD, is most likely due to the diminished content of lysophosphosphatidylcholine
      (lysoPC) within cell membranes caused by the effect of SD on PLA2. The decrease
      in diacylglycerol (DAG) and inositol 1,4,5-triphosphate (IP3) due to inhibition
      of PLC(gamma)1, leads to the downregulation of Ca2+-dependent processes within
      the cell and also inhibits the formation of tumors. These findings support our
      previous data suggesting that SD may have significant potential in the treatment
      of melanoma.

PMID- 23170078
TI  - Antioxidant and anti-protease activities of diazepinomicin from the sponge
      associated Micromonospora strain RV115.
AB  - Diazepinomicin is a dibenzodiazepine alkaloid with an unusual structure among the
      known microbial metabolites discovered so far. Diazepinomicin was isolated from
      the marine sponge-associated strain Micromonospora sp. RV115 and was identified
      by spectroscopic analysis and by comparison to literature data. In addition to
      its interesting preclinical broad-spectrum antitumor potential, we report here
      new antioxidant and anti-protease activities for this compound. Using the ferric
      reducing antioxidant power (FRAP) assay, a strong antioxidant potential of
      diazepinomicin was demonstrated. Moreover, diazepinomicin showed a significant
      antioxidant and protective capacity from genomic damage induced by the reactive
      oxygen species hydrogen peroxide in human kidney (HK-2) and human promyelocytic
      (HL-60) cell lines. Additionally, diazepinomicin inhibited the proteases
      rhodesain and cathepsin L at an IC50 of 70-90 uM. It also showed antiparasitic
      activity against trypomastigote forms of Trypanosoma brucei with an IC50 of 13.5
      uM. These results showed unprecedented antioxidant and anti-protease activities
      of diazepinomicin, thus further highlighting its potential as a future drug
      candidate.

PMID- 23170077
TI  - Marine cyanobacteria compounds with anticancer properties: a review on the
      implication of apoptosis.
AB  - Marine cyanobacteria have been considered a rich source of secondary metabolites
      with potential biotechnological applications, namely in the pharmacological
      field. Chemically diverse compounds were found to induce cytoxicity, anti
      inflammatory and antibacterial activities. The potential of marine cyanobacteria
      as anticancer agents has however been the most explored and, besides cytotoxicity
      in tumor cell lines, several compounds have emerged as templates for the
      development of new anticancer drugs. The mechanisms implicated in the
      cytotoxicity of marine cyanobacteria compounds in tumor cell lines are still
      largely overlooked but several studies point to an implication in apoptosis. This
      association has been related to several apoptotic indicators such as cell cycle
      arrest, mitochondrial dysfunctions and oxidative damage, alterations in caspase
      cascade, alterations in specific proteins levels and alterations in the membrane
      sodium dynamics. In the present paper a compilation of the described marine
      cyanobacterial compounds with potential anticancer properties is presented and a
      review on the implication of apoptosis as the mechanism of cell death is
      discussed.

PMID- 23170079
TI  - Anti-human rhinoviral activity of polybromocatechol compounds isolated from the
      rhodophyta, Neorhodomela aculeata.
AB  - An extract of the red alga, Neorhodomela aculeata, exhibited antiviral activity
      against human rhinoviruses. Bioassay-guided purification was performed to yield
      six compounds, which were subsequently identified as lanosol (1) and five
      polybromocatechols (2-6) by spectroscopic methods, including 1D and 2D NMR and
      mass spectrometric analyses. Structurally, all of these compounds, except
      compound 5, contain one or two 2,3-dibromo-4,5-dihydroxyphenyl moieties. In a
      biological activity assay, compound 1 was found to possess antiviral activity
      with a 50% inhibitory concentration (IC50) of 2.50 MUg/mL against HRV2. Compound
      3 showed anti-HRV2 activity, with an IC50 of 7.11 MUg/mL, and anti-HRV3 activity,
      with an IC50 of 4.69 MUg/mL, without demonstrable cytotoxicity at a concentration
      of 20 MUg/mL. Collectively, the results suggest that compounds 1 and 3 are
      candidates for novel therapeutics against two different groups of human
      rhinovirus.

PMID- 23170080
TI  - Biosynthetic studies on water-soluble derivative 5c (DTX5c).
AB  - The dinoflagellate Prorocentrum belizeanum is responsible for the production of
      several toxins involved in the red tide phenomenon known as Diarrhetic Shellfish
      Poisoning (DSP). In this paper we report on the biosynthetic origin of an okadaic
      acid water-soluble ester derivative, DTX5c, on the basis of the spectroscopical
      analysis of 13C enriched samples obtained by addition of labelled sodium [l-13C],
      [2-13C] acetate to artificial cultures of this dinoflagellate.

PMID- 23170081
TI  - Echinohalimane A, a bioactive halimane-type diterpenoid from a Formosan gorgonian
      Echinomuricea sp. (Plexauridae).
AB  - A new halimane-type diterpenoid, echinohalimane A (1), was isolated from a
      gorgonian, identified as Echinomuricea sp. The structure of 1 was determined by
      spectroscopic methods and this compound was found to exhibit cytotoxicity toward
      various tumor cells and display an inhibitory effect on the release of elastase
      by human neutrophils. Echinohalimane A (1) is the first halimane analogue from
      the marine organisms belonging to phylum Cnidaria.

PMID- 23170082
TI  - Cytotoxic activity of semi-synthetic derivatives of elatol and isoobtusol.
AB  - In the present study, the in vitro cytotoxic effects of six semi-synthetic
      derivatives of elatol (1) and isoobtusol (2) were investigated. Chemical
      modifications were performed on the hydroxyl groups aiming to get derivatives of
      different polarity, namely the hemisuccinate, carbamate and sulfamate. The
      structural elucidation of the new derivatives was based on detailed NMR and MS
      spectroscopic analyses. The in vitro cytotoxicity of compounds 1 to 8 was
      evaluated against A459 and RD tumor cell lines with CC50 values ranging from 4.93
      to 41.53 uM. These results suggest that the structural modifications performed on
      both compounds could be considered a good strategy to obtain more active
      derivatives.

PMID- 23170083
TI  - Digital marine bioprospecting: mining new neurotoxin drug candidates from the
      transcriptomes of cold-water sea anemones.
AB  - Marine bioprospecting is the search for new marine bioactive compounds and large
      scale screening in extracts represents the traditional approach. Here, we report
      an alternative complementary protocol, called digital marine bioprospecting,
      based on deep sequencing of transcriptomes. We sequenced the transcriptomes from
      the adult polyp stage of two cold-water sea anemones, Bolocera tuediae and
      Hormathia digitata. We generated approximately 1.1 million quality-filtered
      sequencing reads by 454 pyrosequencing, which were assembled into approximately
      120,000 contigs and 220,000 single reads. Based on annotation and gene ontology
      analysis we profiled the expressed mRNA transcripts according to known biological
      processes. As a proof-of-concept we identified polypeptide toxins with a
      potential blocking activity on sodium and potassium voltage-gated channels from
      digital transcriptome libraries.

PMID- 23170084
TI  - Assessment of the bacteriocinogenic potential of marine bacteria reveals
      lichenicidin production by seaweed-derived Bacillus spp.
AB  - The objectives of this study were (1) to assess the bacteriocinogenic potential
      of bacteria derived mainly from seaweed, but also sand and seawater, (2) to
      identify at least some of the bacteriocins produced, if any and (3) to determine
      if they are unique to the marine environment and/or novel. Fifteen Bacillus
      licheniformis or pumilus isolates with antimicrobial activity against at least
      one of the indicator bacteria used were recovered. Some, at least, of the
      antimicrobials produced were bacteriocins, as they were proteinaceous and the
      producers displayed immunity. Screening with PCR primers for known Bacillus
      bacteriocins revealed that three seaweed-derived Bacillus licheniformis harbored
      the bli04127 gene which encodes one of the peptides of the two-peptide
      lantibiotic lichenicidin. Production of both lichenicidin peptides was then
      confirmed by mass spectrometry. This is the first definitive proof of bacteriocin
      production by seaweed-derived bacteria. The authors acknowledge that the
      bacteriocin produced has previously been discovered and is not unique to the
      marine environment. However, the other marine isolates likely produce novel
      bacteriocins, as none harboured genes for known Bacillus bacteriocins.

PMID- 23170085
TI  - Ammonificins C and D, hydroxyethylamine chromene derivatives from a cultured
      marine hydrothermal vent bacterium, Thermovibrio ammonificans.
AB  - Chemical and biological investigation of the cultured marine hydrothermal vent
      bacterium, Thermovibrio ammonifican led to the isolation of two hydroxyethylamine
      chromene derivatives, ammonificins C and D. Their structures were elucidated
      using combination of NMR and mass spectrometry. Absolute stereochemistry was
      ascertained by comparison of experimental and calculated CD spectra. Biological
      evaluation and assessment were determined using the patented ApopScreen cell
      based screen for apoptosis-induction. Ammonificins C and D induce apoptosis in
      micromolar concentrations. To our knowledge, this finding is the first report of
      chemical compounds that induce apoptosis from the cultured deep-sea marine
      organism, hydrothermal vent bacterium, Thermovibrio ammonificans.

PMID- 23170086
TI  - Current status on marine products with reversal effect on cancer multidrug
      resistance.
AB  - The resistance of tumor cells to a broad range of anticancer agents continues to
      be a problem for the success of cancer chemotherapy. Multidrug resistance (MDR)
      is due in part to three drug transporter proteins: ABCB1/P-glycoprotein (P-gp),
      ABCC1/multidrug resistance protein 1 (MRP1) and ABCG2/breast cancer resistance
      protein (BCRP). These transporters are part of the ATP-binding cassette (ABC)
      superfamily, whose members function as ATP-dependent drug-efflux pumps. Their
      activity can be blocked by various drugs such as verapamil (calcium channel
      blocker) and cyclosporin A (immunosuppressive agent), etc. These compounds are
      called MDR modulators or reversals. This review highlights several marine natural
      products with reversal effect on multidrug resistance in cancer, including
      agosterol A, ecteinascidin 743, sipholane triterpenoids, bryostatin 1, and
      welwitindolinones.

PMID- 23170087
TI  - Polymethoxy-1-alkenes from Aphanizomenon ovalisporum inhibit vertebrate
      development in the zebrafish (Danio rerio) embryo model.
AB  - Cyanobacteria are recognized producers of a wide array of toxic or otherwise
      bioactive secondary metabolites. The present study utilized the zebrafish (Danio
      rerio) embryo as an aquatic animal model of vertebrate development to identify,
      purify and characterize lipophilic inhibitors of development (i.e., developmental
      toxins) from an isolate of the freshwater cyanobacterial species, Aphanizomenon
      ovalisporum.Bioassay-guided fractionation led to the purification, and subsequent
      chemical characterization, of an apparent homologous series of isotactic
      polymethoxy-1-alkenes (1-6), including three congeners (4-6) previously
      identified from the strain, and two variants previously identified from other
      species (2 and 3), as well as one apparently novel member of the series (1). Five
      of the PMAs in the series (1-5) were purified in sufficient quantity for
      comparative toxicological characterization, and toxicity in the zebrafish embryo
      model was found to generally correlate with relative chain length and/or
      methoxylation. Moreover, exposure of embryos to a combination of variants
      indicates an apparent synergistic interaction between the congeners. Although
      PMAs have been identified previously in cyanobacteria, this is the first report
      of their apparent toxicity. These results, along with the previously reported
      presence of the PMAs from several cyanobacterial species, suggest a possibly
      widespread distribution of the PMAs as toxic secondary metabolites and warrants
      further chemical and toxicological investigation.

PMID- 23170088
TI  - Effects of oral administration of fucoidan extracted from Cladosiphon okamuranus
      on tumor growth and survival time in a tumor-bearing mouse model.
AB  - We evaluated the anti-tumor activities of the oral administration of fucoidan
      extracted from Cladosiphon okamuranus using a tumor (colon 26)-bearing mouse
      model. The materials used included low-molecular-weight fucoidan (LMWF: 6.5-40
      kDa), intermediate-molecular-weight fucoidan (IMWF: 110-138 kDa) and high
      molecular-weight fucoidan (HMWF: 300-330 kDa). The IMWF group showed
      significantly suppressed tumor growth. The LMWF and HMWF groups showed
      significantly increased survival times compared with that observed in the control
      group (mice fed a fucoidan-free diet). The median survival times in the control,
      LMWF, IMWF and HMWF groups were 23, 46, 40 and 43 days, respectively. It was also
      found that oral administration of fucoidan increased the population of natural
      killer cells in the spleen. Furthermore, from the results of the experiment using
      Myd-88 knockout mice, it was found that these effects are related to gut
      immunity. These results suggest that fucoidan is a candidate anti-tumor
      functional food.

PMID- 23170090
TI  - A Message From the Editor-in-Chief.

PMID- 23170089
TI  - omega-Conotoxin GVIA mimetics that bind and inhibit neuronal Ca(v)2.2 ion
      channels.
AB  - The neuronal voltage-gated N-type calcium channel (Ca(v)2.2) is a validated
      target for the treatment of neuropathic pain. A small library of anthranilamide
      derived omega-Conotoxin GVIA mimetics bearing the diphenylmethylpiperazine moiety
      were prepared and tested using three experimental measures of calcium channel
      blockade. These consisted of a 125I-omega-conotoxin GVIA displacement assay, a
      fluorescence-based calcium response assay with SH-SY5Y neuroblastoma cells, and a
      whole-cell patch clamp electrophysiology assay with HEK293 cells stably
      expressing human Ca(v)2.2 channels. A subset of compounds were active in all
      three assays. This is the first time that compounds designed to be mimics of
      omega-conotoxin GVIA and found to be active in the 125I-omega-conotoxin GVIA
      displacement assay have also been shown to block functional ion channels in a
      dose-dependent manner.

PMID- 23170091
TI  - Percutaneous pulmonary valve implantation.
AB  - Pulmonary regurgitation (PR) is a frequent sequelae after repair of tetralogy of
      Fallot, pulmonary atresia, truncus arteriosus, Rastelli and Ross operation. Due
      to patient growth and conduit degeneration, these conduits have to be changed
      frequently due to regurgitation or stenosis. However, morbidity is significant in
      these repeated operations. To prolong conduit longevity, bare-metal stenting in
      the right ventricular outflow tract (RVOT) obstruction has been performed.
      Stenting the RVOT can reduce the right ventricular pressure and symptomatic
      improvement, but it causes PR with detrimental effects on the right ventricle
      function and risks of arrhythmia. Percutaneous pulmonary valve implantation has
      been shown to be a safe and effective treatment for patients with pulmonary valve
      insufficiency, or stenotic RVOTs.

PMID- 23170092
TI  - The risk model for prediction of survival in heart failure.

PMID- 23170094
TI  - Hypoadiponectinemia in patients with paroxysmal atrial fibrillation.
AB  - BACKGROUND AND OBJECTIVES: Adiponectin is an adipose tissue-derived hormone that
      has beneficial effects on cardiac function and has been reported to be associated
      with lipid metabolism, glucose metabolism, and insulin resistance. Serum levels
      of adiponectin are reduced in obese individuals compared with non-obese
      individuals. Obesity is associated with an increased incidence of atrial
      fibrillation (AF); however, the role of adiponectin in AF is unclear. The aim of
      this study is to evaluate the relationship between the plasma adiponectin level
      and AF. SUBJECTS AND METHODS: Sixty-one consecutive patients were prospectively
      enrolled for this study. Subjects were divided into two groups: patients with AF
      (n=30) and controls (n=31). Laboratory evaluation, including levels of plasma
      adiponectin, was performed and echocardiographic parameters were measured.
      RESULTS: The baseline characteristics were not different between the two groups.
      The plasma adiponectin level of patients in the AF group was significantly lower
      than in the control group (14.9+/-7.2 vs. 19.+/-8.9 ug/mL, p<0.05). In addition,
      when we divided the AF patients into paroxysmal and chronic AF, the plasma
      adiponectin level was significantly lower in patients with paroxysmal AF,
      compared with the control group. In multiple binary logistic regression analysis
      to evaluate the independent predictors for AF, adiponectin and left atrial
      diameter were strong independent predictors of AF. CONCLUSION: In this study a
      lower plasma adiponectin concentration was significantly associated with that of
      paroxysmal AF. Hypoadiponectinemia can potentially be an important risk factor
      for AF.

PMID- 23170093
TI  - Prognostic Estimation of Advanced Heart Failure With Low Left Ventricular
      Ejection Fraction and Wide QRS Interval.
AB  - BACKGROUND AND OBJECTIVES: Cardiac resynchronization therapy (CRT) has been known
      to improve the outcome of advanced heart failure (HF) but is still underutilized
      in clinical practice. We investigated the prognosis of patients with advanced HF
      who were suitable for CRT but were treated with conventional strategies. We also
      developed a risk model to predict mortality to improve the facilitation of CRT.
      SUBJECTS AND METHODS: Patients with symptomatic HF with left ventricular ejection
      fraction <=35% and QRS interval >120 ms were consecutively enrolled at
      cardiovascular hospital. After excluding those patients who had received device
      therapy, 239 patients (160 males, mean 67+/-11 years) were eventually recruited.
      RESULTS: During a follow-up of 308+/-236 days, 56 (23%) patients died. Prior
      stroke, heart rate >90 bpm, serum Na <=135 mEq/L, and serum creatinine >=1.5
      mg/dL were identified as independent factors using Cox proportional hazards
      regression. Based on the risk model, points were assigned to each of the risk
      factors proportional to the regression coefficient, and patients were stratified
      into three risk groups: low- (0), intermediate-(1-5), and high-risk (>5 points).
      The 2-year mortality rates of each risk group were 5, 31, and 64 percent,
      respectively. The C statistic of the risk model was 0.78, and the model was
      validated in a cohort from a different institution where the C statistic was
      0.80. CONCLUSION: The mortality of patients with advanced HF who were managed
      conventionally was effectively stratified using a risk model. It may be useful
      for clinicians to be more proactive about adopting CRT to improve patient
      prognosis.

PMID- 23170095
TI  - Absence and Resolution of Fragmented QRS Predict Reversible Myocardial Ischemia
      With Higher Probability of ST Segment Resolution in Patients With ST Segment
      Elevation Myocardial Infarction.
AB  - BACKGROUND AND OBJECTIVES: Fragmented QRS complexes (fQRS) are associated with
      increased morbidity and mortality. The causative relationship between fQRS and
      cardiac fibrosis has been shown, but whether the presence and the number of fQRS
      on admission of electrocardiogram (ECG) predicts ST segment resolution in
      patients undergoing primary percutaneous coronary intervention (p-PCI) has not
      been investigated until now. SUBJECTS AND METHODS: This study included one
      hundred and eighty-four consecutive patients with ST elevation myocardial
      infarction (STEMI) who underwent p-PCI. The presence or absence of fQRS on pre
      and post-PCI ECG and their relation with myocardial infarction and reperfusion
      parameters were investigated. RESULTS: Patients with fQRS on admission of ECG or
      newly developed fQRS after p-PCI had increased inflammatory markers, higher
      cardiac enzyme levels, increased pain to balloon time, prolonged QRS time, more
      extended coronary involvement and more frequent Q waves on ECG in comparison to
      patients with absence or resolved fQRS. The presence and higher number of fQRS on
      admission or post-PCI ECGs were significantly related with low percent of ST
      resolution and myocardial reperfusion parameters. The area under the receiver
      operating characteristics curve values for the presence and number of fQRS to
      detect Thrombolysis in Myocardial Infarction Blush Grade 0 and 1, were 0.682 and
      0.703. CONCLUSION: In our study, fQRS was significantly related to infarction and
      myocardial reperfusion parameters before and after p-PCI. Successful myocardial
      reperfusion by p-PCI caused the reduction in number of fQRS and QRS time with
      higher ST resolution. fQRS may be useful in identifying the patients at higher
      cardiac risk with increased ischemic jeopardized or infarcted myocardium, and
      persistent or newly developed fQRS may predict low percent of ST segment
      resolution in patients undergoing p-PCI.

PMID- 23170096
TI  - Transcatheter aortic valve implantation: early experience in Korea.
AB  - BACKGROUND AND OBJECTIVES: Transcatheter aortic valve implantation (TAVI) was
      recently introduced in Korea. The present report describes the experience of
      early TAVI cases. SUBJECTS AND METHODS: Between March, 2010 and October, 2011, 48
      patients with severe symptomatic aortic stenosis (AS) were screened at the Asan
      Medical Center to determine their suitability for surgical intervention. Of
      these, 23 were considered unsuitable and underwent TAVI. Procedural success
      rates, procedure-related complications, and clinical outcomes were evaluated in
      the TAVI patients. RESULTS: Transfemoral (n=20) or transapical (n=3) TAVI was
      performed. The mean age of patients was 75.9+/-5.4 years and 57% were females.
      The mean logistic European System for Cardiac Operative Risk Evaluation was
      25.6+/-5.1%. Implantation was successful in 22 patients (19 transfemoral, three
      transapical). After successful implantation, the mean aortic valve area increased
      from 0.68+/-0.14 cm(2) to 1.45+/-0.33 cm(2). There were no procedure-related
      complications or mortality. The patients showed no paravalvular aortic
      regurgitation with >= moderate degree and remained stable without progression
      during follow-up. During follow-up (interquartile range, 1.1-12.9), all patients
      were alive without any occurrence of valve failure. CONCLUSION: TAVI procedure is
      feasible in patients with inoperative symptomatic AS leading to hemodynamic and
      clinical improvement. With accumulation of experience, proper patient selection
      and development of device technologies, TAVI should decrease adverse events and
      expand the indications in the near future.

PMID- 23170097
TI  - Predictors of long-term survival in acute coronary syndrome patients with left
      ventricular dysfunction after percutaneous coronary intervention.
AB  - BACKGROUND AND OBJECTIVES: Predictive factors of mortality in acute coronary
      syndrome (ACS) patients with left ventricular dysfunction were analyzed during 5
      year clinical follow-up after percutaneous coronary intervention (PCI). SUBJECTS
      AND METHODS: A total of 329 ACS consecutive patients (64.6+/-11.3 years, 227
      males) who underwent PCI from January 2001 to March 2006 were followed for 5
      years. All patients had lower than 40% of left ventricular ejection fraction
      (LVEF). Patients were divided into Group I (survived longer than 5-years: n=130,
      101 males) and Group II (survived shorter than 5 years: n=199, 126 males).
      RESULTS: The cumulative survival rate was 88.0% at 1 month, 78.0% at 6 months,
      75.0% at 1 year, 67.0% at 2 years, 62.0% at 3 years, 57.0% at 4 years and 40% at
      5-years. Group II was older (61.6+/-11.2 years vs. 66.4+/-11.4 years, p<0.001),
      and showed higher prevalence of female gender (28.4% vs. 36.7%, p=0.006) and
      lower LVEF (35.3+/-5.2 vs. 33.6+/-5.6) than Group I. The independent predictors
      for mortality were LVEF <30% {odds ratio (OR)=1.793, 95% confidence interval
      (CI): 1.234-2.452, p=0.002}, serum creatinine >3.0 mg/dL (OR=2.455, 95% CI: 1.306
      4.614, p=0.005), older than 65 years (OR=1.594, 95% CI: 1.152-2.206, p=0.005),
      and female gender (OR=1.524, 95% CI: 1.090-2.130, p=0.014). CONCLUSION: Five-year
      survival rate was 40% in ACS patients with left ventricular dysfunction, and the
      predictors for mortality were low LVEF, high serum creatinine, old age, and
      female gender.

PMID- 23170098
TI  - Exercise-induced intranodal atrioventricular block.
AB  - Exercise-induced atrioventricular (AV) block in patients with normal AV
      conduction at rest is rare. Herein, we describe the case of a 67-year-old woman
      with normal 1 : 1 AV conduction at rest, who developed complete AV block during a
      treadmill test. Our patient complained of effort-related dizziness and dyspnea,
      which had been ongoing for 3 months. The patient's physical examination was
      normal. The resting electrocardiogram showed left anterior fascicular block with
      a PR interval of 0.19 seconds. The echocardiogram was normal except for mild
      aortic valve regurgitation. During the treadmill test, the patient developed
      complete AV block at a sinus rate of 90 beats/min, which was followed by 2 : 1 AV
      block associated with dyspnea and dizziness. The patient's coronary angiogram was
      normal, and the ergonovine provocation test was negative. Electrophysiological
      studies demonstrated rate-dependent intranodal AV block. The patient received
      implantation of a permanent dual chamber (DDD) pacemaker and had no further
      symptoms during the follow-up period.

PMID- 23170099
TI  - An unusual case of left ventricular free wall rupture caused by a silent
      myocardial infarction.
AB  - Left ventricular free wall rupture (LVFWR) is a serious complication of
      myocardial infarction. It presents with a very high mortality rate and can be
      rescued by accurate diagnosis and emergency surgery. LVFWR can occur with sudden
      overt clinical symptoms or present insidiously. This report highlights the case
      of a man with no prior history of coronary artery disease, who presented with
      LVFWR and pericardial effusion that evolved to severe bacterial pericarditis.

PMID- 23170100
TI  - A case of left ventricular noncompaction accompanying fasciculo-ventricular
      accessory pathway and atrial flutter.
AB  - Left ventricular hypertrabeculation/noncompaction (LVHT) is an uncommon type of
      genetic cardiomyopathy characterized by trabeculations and recesses within the
      ventricular myocardium. LVHT is associated with diastolic or systolic
      dysfunction, thromboembolic complications, and arrhythmias, including atrial
      fibrillation, ventricular arrhythmias, atrioventricular block and Wolff-Parkinson
      White syndrome. Herein, we describe a patient who presented with heart failure
      and wide-complex tachycardia. Echocardiography showed LVHT accompanied with
      severe mitral regurgitation. The electrophysiologic study revealed a fasciculo
      ventricular accessory pathway and atrial flutter (AFL). The AFL was successfully
      treated with catheter ablation.

PMID- 23170101
TI  - A case of acute myopericarditis associated with Mycoplasma pneumoniae infection
      in a child.
AB  - Mycoplasma pneumoniae (M. pneumoniae) primarily causes respiratory tract
      infections in persons aged 5-20 years. Tracheobronchitis and bronchopneumonia are
      the most commonly recognized clinical symptoms associated with M. pneumoniae
      infection. Complications of this infection are unusual; in particular, cardiac
      involvement is very rare and is generally accompanied by pneumonia.
      Nonrespiratory illness can therefore involve direct invasion by M. pneumoniae or
      autoimmune mechanisms, as suggested by the frequency of cross reaction between
      human antigens and M. pneumoniae. Herein, we report a case of severe acute
      myopericarditis with pneumonia caused by M. pneumoniae in a healthy young child
      who presented with fever, lethargy, oliguria and dyspnea. She survived with
      aggressive therapy including clarithromycin, intravenous immunoglobulin,
      inotropics, and diuretics. The patient was discharged on the 19th day after
      admission and followed up 1 month thereafter at the outpatient clinic without
      sequelae.

PMID- 23170102
TI  - Severe form of persistent thebesian veins presenting as ischemic heart disease.
AB  - Coronary artery fistula is a rare congenital anomaly. Most patients with this
      anomaly are asymptomatic, but some may develop heart failure, myocardial ischemia
      or arrhythmias. We report a case of a patient who presented with myocardial
      ischemia secondary to persistent Thebesian veins. Coronary angiography
      demonstrated a marked capillary blush draining into the left ventricular cavity
      through multiple microfistulae from the left anterior descending artery, left
      circumflex artery and right coronary artery. The patient was discharged without
      chest pain and was medically maintained with a beta-blocker and angiotensin
      converting enzyme inhibitor.

PMID- 23170103
TI  - Familial occurrence of atrioventricular nodal reentrant tachycardia in a mother
      and her son.
AB  - Atrioventricular nodal reentrant tachycardia (AVNRT), caused by a reentry circuit
      involving fast and slow atrioventricular nodal pathways, is one of the most
      common types of paroxysmal supraventricular tachycardias. While familial Wolff
      Parkinson-White syndrome has been well recognized, familial AVNRT has been rarely
      reported. We report a familial occurrence of AVNRT in a mother and her son, who
      were symptomatic and successfully treated with radiofrequency catheter ablation
      of slow pathway.

PMID- 23170104
TI  - Alternating ventricular preexcitation.

PMID- 23170106
TI  - First-line single-agent chemotherapy for patients with recurrent or metastatic
      gastric cancer with poor performance status.
AB  - Combination chemotherapy is a standard treatment approach in advanced gastric
      cancer. However, combination chemotherapy for advanced gastric cancer is often
      associated with severe treatment-related toxicities and most oncologists are
      reluctant to perform combination chemotherapy in patients with a poor clinical
      condition. We retrospectively investigated the efficacy and tolerability of
      single-agent chemotherapy in patients with recurrent or metastatic gastric cancer
      with poor performance status (PS). We reviewed advanced gastric adenocarcinoma
      patients who received first-line single-agent palliative chemotherapy due to poor
      PS between June 2006 and December 2010. A total of 125 patients with Eastern
      Cooperative Oncology Group (ECOG) PS 2-3, whose general condition did not allow
      combination chemotherapy, were enrolled. Four single agents were used: TS-1
      (n=63), paclitaxel (n=42), irinotecan (n=15) and capecitabine (n=5). The median
      age was 66 years, with a range of 25-81 years. The percent response rate and rate
      of stable disease (SD) were 19.2 and 35.2%, respectively, giving a disease
      control rate of 54.4%. The median progression-free survival (PFS) was 3.9 months
      (95% CI, 2.73-5.06). The median overall survival (OS) was 9.1 months (95% CI,
      7.70-10.56) with a 1-year survival rate of 31.2%. Multivariate analysis
      demonstrated that the independent prognostic factors for OS were chemotherapy
      regimen (capecitabine) [reference: TS-1, hazard ratio (HR), 5.00; 95% CI, 1.81
      13.81; P=0.002], no second-line chemotherapy (HR, 2.3; 95% CI, 1.48-3.57;
      P=0.001), bone metastasis (HR, 2.73; 95% CI, 1.22-6.09; P=0.014), ECOG PS 3 (HR,
      38.10; 95% CI, 13.72-105.78; P=0.001), Glasgow prognostic score (GPS) >=1 (HR,
      1.88; 95% CI, 1.24-2.85; P=0.003) and chemotherapy response [SD + progressive
      disease (PD) + not evaluable (NE); HR, 2.37; 95% CI, 1.39-4.05; P=0.002)]. First
      line single-agent palliative chemotherapy demonstrated a relatively good clinical
      efficacy for recurrent or metastatic gastric cancer patients with poor PS.

PMID- 23170105
TI  - Genotoxicity and carcinogenicity of cobalt-, nickel- and copper-based
      nanoparticles.
AB  - The nanotechnology industry has matured and expanded at a rapid pace in the last
      decade, leading to the research and development of nanomaterials with enormous
      potential. The largest source of these nanomaterials is the transitional metals.
      It has been revealed that numerous properties of these nano-sized elements are
      not present in their bulk states. The nano size of these particles means they are
      easily transported into biological systems, thus, raising the question of their
      effects on the susceptible systems. Although advances have been made and insights
      have been gained on the effect of transitional metals on susceptible biological
      systems, there still is much ground to be covered, particularly with respect to
      our knowledge on the genotoxic and carcinogenic effects. Therefore, this review
      intends to summarize the current knowledge on the genotoxic and carcinogenic
      potential of cobalt-, nickel- and copper-based nanoparticles indicated in in
      vitro and in vivo mammalian studies. In the present review, we briefly state the
      sources, use and exposure routes of these nanoparticles and summarize the current
      literature findings on their in vivo and in vitro genotoxic and carcinogenic
      effects. Due to the increasing evidence of their role in carcinogenicity, we have
      also included studies that have reported epigenetic factors, such as abnormal
      apoptosis, enhanced oxidative stress and pro-inflammatory effects involving these
      nanoparticles.

PMID- 23170107
TI  - MDM2 SNP309 polymorphism is associated with lung cancer risk in women: A meta
      analysis using METAGEN.
AB  - Lung cancer is the most common diagnosed malignancy and the leading cause of
      cancer-related mortality worldwide. Murine double minute 2 (MDM2) SNP309
      polymorphisms have been reported to influence the risk of lung cancer. However,
      the published studies together with four subsequent meta-analyses have yielded
      contradictory results. To examine this inconsistency, we conducted a meta
      analysis of 6,696 lung cancer cases and 7,972 controls from eight published case
      control studies using METAGEN. Odds ratios (ORs) with 95% confidence intervals
      (CIs) were calculated with STATA software and used to assess the strength of the
      association. In the overall analysis, a significant association between MDM2
      SNP309 polymorphism and lung cancer risk was observed (OR, 1.143; 95% CI, 1.047
      1.247). Moreover, stratified by ethnicity, a significant association was found in
      Asians (OR, 1.260; 95% CI, 1.111-1.429), but not in Europeans. Subgroup analysis
      of gender, histology and smoking status suggested that the MDM2 SNP309 genotype
      was associated with increased lung cancer risk in women (OR, 1.282; 95% CI, 1.062
      1.548) and never smokers (OR, 1.328; 95% CI, 1.119-1.575). No statistically
      significant association was observed in males and ever smoking population, and no
      association was found in subgroup analysis based on histology. In conclusion, the
      association between MDM2 SNP309 and lung cancer was statistically significant,
      particularly in Asians, women and never smoking population.

PMID- 23170108
TI  - Evaluation of the effect of a chicken comb extract-containing supplement on
      cartilage and bone metabolism in athletes.
AB  - In a previous study, we revealed that a commercially available product of dietary
      supplement containing a chicken comb extract (CCE), which is rich in hyaluronan,
      not only relieves joint pain and other symptoms, but also potentially improves
      the balance of type II collagen degradation/synthesis in patients with knee
      osteoarthritis. Since soccer is one of the sports most likely to cause knee
      osteoarthritis (OA), we evaluated the effect of a CCE-containing supplement on
      cartilage and bone metabolism in athletes. Fourteen and 15 subjects (all
      midfielders) were randomly assigned to receive the test product (test group) and
      the dummy placebo containing only vehicle (placebo group), respectively, for 12
      weeks. The daily oral intake of the CCE-containing test product clearly decreased
      the urinary levels of both C-terminal crosslinked telopeptides of cartilage
      specific type II collagen (CTX-II) as a type II collagen degradation marker and
      the N-terminal telopeptides of bone-specific type I collagen (NTx) as a marker of
      bone resorption at 12 weeks after the initiation of the intervention. By
      contrast, no significant reduction was detected in the placebo group at any
      timepoint during the intervention. These observations indicate that the test
      product is effective in inhibiting, not only cartilage degradation, but also bone
      remodeling. Thus, the CCE-containing supplement may be useful for the management
      of joint health in athletes.

PMID- 23170109
TI  - Serum prohepcidin levels are potential prognostic markers in patients with
      multiple myeloma.
AB  - Prohepcidin is the prohormone of hepcidin. Anemia is one of the main clinical
      features in patients with multiple myeloma (MM) and hepcidin may be associated
      with iron homeostasis in these patients. However, the clinical significance of
      prohepcidin is not fully understood. In this retrospective study, we measured
      serum prohepcidin levels using an immunoassay technique to study its clinical
      significance in 39 MM patients. Serum prohepcidin levels in patients with MM were
      weakly correlated with alkaline phosphatase (ALP) levels (r=0.32, P=0.048),
      calculated by Spearman's rank correlation, but not with other clinical data,
      including hemoglobin, serum iron or ferritin. In addition, patients with severe
      renal insufficiency [creatinine clearance (CCr) <50 ml/min] had significantly
      higher prohepcidin levels compared with patients with mild or no renal
      insufficiency (CCr >=50 ml/min, P=0.047). In contrast, low serum prohepcidin
      levels less than 110 ng/ml were an independent predictor of poor overall survival
      [hazard ratio (HR), 5.29; 95% confidence interval (CI), 1.65-17.03] in addition
      to serum creatinine levels of at least 2 mg/dl (HR, 5.32; CI, 1.10-25.64), serum
      calcium (HR, 3.53; CI, 1.01-12.33) and ECOG performance status grade 4 (HR, 4.15;
      CI, 1.32-13.09) in the multivariate analysis using Cox proportional hazards
      model. In the subset of 31 MM patients with CCr >=50 ml/min, low serum
      prohepcidin (HR, 5.65; CI, 1.60-19.95) was an indicator of poor prognosis in
      multivariate analysis. These results indicate that serum prohepcidin levels may
      be associated with ALP and renal function but not iron homeostasis, in MM
      patients. In addition, lower serum prohepcidin levels are potential independent
      indicators of poor overall survival in MM patients regardless of renal function.

PMID- 23170110
TI  - Expression of thymidylate synthase and orotate phosphoribosyltransferase in
      thymic carcinoma.
AB  - Thymic carcinoma is a rare thymic epithelial tumor in which chemotherapy for
      advanced disease has not yet been established. Thymidylate synthase (TS) and
      orotate phosphoribosyltransferase (OPRT) protein expression levels in thymic
      carcinoma were evaluated as possible indicators of the anticancer activity of 5
      fluorouracil (5-FU) drugs using immunohistochemistry (IHC). A total of 24 samples
      of thymic carcinoma were used in the present study. The tumor sections were
      immunohistochemically stained for TS and OPRT. As a comparison with thymic
      carcinoma, we also assessed the TS and OPRT protein expression levels in 55 lung
      cancer samples. The TS expression was positive in 12 of 24 thymic carcinoma
      samples (50%) and OPRT expression was positive in 10 (42%). The association
      between TS and OPRT expression and Masaoka stages of thymic carcinoma was
      analyzed. The TS and OPRT expressions in stage IV were significantly higher
      compared to that in stages I, II or III. We also compared the TS and OPRT
      expression levels between thymic carcinoma and lung cancer (33 adenocarcinomas
      and 22 squamous cell carcinomas). TS expression in thymic carcinoma was
      significantly lower compared with lung squamous cell carcinoma. OPRT expression
      in thymic carcinoma was significantly higher compared to lung adenocarcinoma. The
      combination of a relatively low expression of TS and high expression of OPRT
      suggests an improved antitumor effect of 5-FU drugs in thymic carcinoma compared
      to in lung carcinoma.

PMID- 23170112
TI  - Stellera chamaejasme L. extract induces apoptosis of human lung cancer cells via
      activation of the death receptor-dependent pathway.
AB  - Stellera chamaejasme L. has been widely used in the treatment of lung, liver and
      esophageal cancer in Chinese traditional medicine. In our previous study, we
      found that the extract of Stellera chamaejasme L. (ESC) inhibited the growth and
      induced the apoptosis of human lung cancer NCI-H157 cells. In the present study,
      we investigated the cellular effects of an ESC-2 extract isolated from ESC in the
      NCI-H157 human lung cancer cell line. We found that ESC-2 inhibited the growth of
      NCI-H157 cells, demonstrating ESC-2-induced morphological changes in cells and
      reduced cell viability in a dose- and time-dependent manner. Furthermore, we
      observed that ESC-2 resulted in apoptosis, activation of caspase-8 and caspase-3,
      and an increase in Fas expression, indicating that the NCI-H157 cell growth
      inhibitory activity of ESC-2 was due to death receptor-dependent pathway-mediated
      apoptosis, which may partly explain the anti-cancer activity of ESC-2.

PMID- 23170111
TI  - Propranolol treatment of infantile hemangioma endothelial cells: A molecular
      analysis.
AB  - Infantile hemangiomas (IHs) are non-malignant, largely cutaneous vascular tumors
      affecting approximately 5-10% of children to varying degrees. During the first
      year of life, these tumors are strongly proliferative, reaching an average size
      ranging from 2 to 20 cm. These lesions subsequently stabilize, undergo a
      spontaneous slow involution and are fully regressed by 5 to 10 years of age.
      Systemic treatment of infants with the non-selective beta-adrenergic receptor
      blocker, propranolol, has demonstrated remarkable efficacy in reducing the size
      and appearance of IHs. However, the mechanism by which this occurs is largely
      unknown. In this study, we sought to understand the molecular mechanisms
      underlying the effectiveness of beta blocker treatment in IHs. Our data reveal
      that propranolol treatment of IH endothelial cells, as well as a panel of normal
      primary endothelial cells, blocks endothelial cell proliferation, migration, and
      formation of the actin cytoskeleton coincident with alterations in vascular
      endothelial growth factor receptor-2 (VEGFR-2), p38 and cofilin signaling.
      Moreover, propranolol induces major alterations in the protein levels of key
      cyclins and cyclin-dependent kinase inhibitors, and modulates global gene
      expression patterns with a particular affect on genes involved in lipid/sterol
      metabolism, cell cycle regulation, angiogenesis and ubiquitination.
      Interestingly, the effects of propranolol were endothelial cell-type independent,
      affecting the properties of IH endothelial cells at similar levels to that
      observed in neonatal dermal microvascular and coronary artery endothelial cells.
      This data suggests that while propranolol markedly inhibits hemangioma and normal
      endothelial cell function, its lack of endothelial cell specificity hints that
      the efficacy of this drug in the treatment of IHs may be more complex than simply
      blockage of endothelial function as previously believed.

PMID- 23170113
TI  - Study of the role of epidermal growth factor on lung fluid transport in rabbits
      with acute lung injury caused by endotoxin.
AB  - The aim of this study was to investigate the effect of epidermal growth factor
      (EGF) on the lung fluid transport of rabbits with acute lung injury caused by
      endotoxin and evaluate its therapeutic action. A total of 24 rabbits were
      randomly divided into control, simple acute lung injury (ALI) and EGF only
      treatment groups. ALI rabbit models were constructed by the administration of
      endotoxin (lipopolysaccharide, LPS) and subsequent treatment with EGF. Arterial
      partial pressure of oxygen, lung pathomorphological changes and wet/dry weight
      (W/D) of the left lobe of lung tissue were observed at various time points.
      Results showed that following treatment with EGF, the breathing status of the
      rabbits continued to improve. An increase was noted in PaO(2) at 12 h after EGF
      treatment and 24 h later PaO(2) had significantly increased. A marked decrease
      was observed in the value of W/D and the exudation was reduced. The extrinsic EGF
      decreased the exudation of pulmonary capillaries and improved lung water
      transport. Our findings verified that epidermal growth factor had repaired the
      effect of ALI through continuous 48-h observation. Therefore, the present study
      demonstrated the therapeutic action of EGF.

PMID- 23170114
TI  - Diet-induced obesity potentiates the growth of gastric cancer in mice.
AB  - Obesity increases the risk of gastric cancer and may affect its development and
      progression, however, the mechanisms underlying this association are completely
      unknown. The purpose of the current study was to investigate the effect of
      obesity on gastric cancer growth by adopting a novel in vivo model. Diet-induced
      obese and lean mice were inoculated with murine forestomach carcinoma cells, and
      studied for 2 weeks. Tumor histology, cellular proliferation and apoptosis were
      evaluated. Serum glucose, insulin, visfatin levels and peripheral CD3(+), CD4(+/
      ), CD8(+/-) lymphocytes were assayed. All mice were alive and developed no
      metastasis, a greater number of obese mice developed palpable tumors than lean
      mice. The tumors from obese mice had a larger volume, greater intratumoral
      adipocyte mass, and exhibited a higher proliferation and reduced apoptosis rate
      compared to those of lean animals. Both serum insulin and visfatin concentrations
      correlated positively with tumor proliferation and negatively with tumor
      apoptosis. Obese mice had a significantly lower level of CD3(+), CD3(+)CD4(+) T
      lymphocytes, and a lower level of CD4(+)/CD8(+) in peripheral blood compared to
      these lymphocyte levels in the lean mice. In conclusion, the altered
      adipocytokine milieu and insulin resistance observed in obesity may lead directly
      to alterations in the tumor microenvironment and cell immunity for avoiding
      cancer, thereby, promoting gastric cancer survival and growth.

PMID- 23170115
TI  - Effect of enhanced expression of COL8A1 on lymphatic metastasis of hepatocellular
      carcinoma in mice.
AB  - The present study aimed to investigate the influence of COL8A1 expression on cell
      invasiveness, drug sensitivity and tumorigenicity of hepatocellular carcinoma
      Hepa1-6 cells with low metastatic potential. COL8A1-1-pEGFP-N2 and pEGFP-N2 were
      transfected into experimental and control group cells. The COL8A1 expression in
      transfected Hepa1-6 cells was analyzed with RT-PCR and western blot analysis. The
      invasive potential of transfected Hepa1-6 cells was tested in invasion
      experiments in vitro and the tumorigenic ability of the transfected Hepa1-6 cells
      was tested in mouse tumors in vivo. Hepa1-6 cell proliferation and D-limonene
      sensitivity was analyzed using the MTT method. Expression of COL8A1 in the Hepa1
      6/COL8A1 group showed a significant increase when compared with the untransfected
      cells of the Hepa1-6 control group and empty-plasmid transfected cells from the
      Hepa1-6/mock control group. Enhanced COL8A1 expression increased cell
      proliferation and matrix adhesion ability via invasion and tumorigenesis in vivo
      while the sensitivity to D-limonene was concurrently inhibited. The expression of
      COL8A1 in hepatocarcinoma cells was correlated with increased tumor cell
      proliferation, invasion, in vivo tumorigenicity and reduced antitumor drug
      sensitivity, and may provide novel targets for tumor therapy.

PMID- 23170116
TI  - Antidepressant effect of geranylgeranylacetone in a chronic mild stress model of
      depression and its possible mechanism.
AB  - Depression is a highly debilitating and widely distributed illness in the general
      population. Geranylgeranylacetone (GGA), a non-toxic anti-ulcer drug, has been
      reported to have protective effects in the central nervous system. The aim of
      this study was to determine the antidepressant effect of GGA in a chronic mild
      stress (CMS) model of depression. We confirmed that CMS in rats caused a
      reduction in locomotor activity and an increase in the levels of monoamine
      oxidase-A (MAO-A) and caspase-3 in the hippocampus. GGA treatment reversed stress
      induced alterations in locomotor activity and target levels of MAO-A and caspase
      3. In addition, GGA treatment induced heat shock protein 70 (Hsp70) expression in
      the hippocampus. These findings suggest that GGA possesses an antidepressant
      activity in a CMS model of depression. The activity of GGA in the relief of
      depression may be mediated via the induction of Hsp70 expression to suppress MAO
      A expression and the apoptosis cascade.

PMID- 23170117
TI  - Relationship between expression and prognostic ability of PTEN, STAT3 and VEGF-C
      in colorectal cancer.
AB  - Expression of phosphatase and tensin homolog deleted on chromosome 10 (PTEN),
      signal transducer and activator of transcription-3 (STAT3) and vascular
      endothelial growth factor-C (VEGF-C) and their relationship with clinico
      pathological features and prognostic ability was determined using
      immunohistochemistry in 68 cases of colorectal cancer with follow-up data. Kaplan
      Meier survival analysis was performed and the prognostic value was determined
      using univariate analysis. PTEN, STAT3 and VEGF-C expression was detected in
      32.4, 60.3 and 63.2% of colorectal carcinoma cases and 90.0, 0 and 0% of normal
      colon samples, respectively. PTEN and STAT3 were correlated with pathological
      grade (p=0.011, p=0.001, respectively), but not with tumor size, lymph node
      metastasis or clinical stage. VEGF-C was correlated with lymph node metastasis
      (p=0.002), but not with tumor size, pathological grade or clinical stage.
      Expression of STAT3 and VEGF-C was negatively correlated with PTEN (r=-0.402, r=
      0.320, respectively), whereas STAT3 and VEGF-C expression was positively
      correlated with PTEN (r=0.254). The 3- and 5-year survival rates of PTEN protein
      positive patients (68.1 and 50.0%, respectively) were significantly higher than
      those of PTEN protein-negative patients (32.6 and 19.6%, respectively; p=0.008).
      The 3- and 5-year survival rates of STAT3-positive (29.3 and 17.1%, respectively)
      were significantly lower than those of STAT3-negative patients (66.7 and 48.1%,
      respectively; p=0.005). The 3- and 5-year survival rates of VEGF-C-positive
      patients (29.3 and 17.1%, respectively) were significantly lower than the rates
      of VEGF-C-negative patients (66.7 and 48.1%, respectively; p=0.003, p=0.004,
      respectively). Multivariate analysis revealed that VEGF-C expression was an
      independent prognostic factor. In conclusion, this study indicates that PTEN,
      STAT3 and VEGF-C expression are beneficial prognostic factors, which may aid in
      the accurate assessment of prognosis and guide clinical treatment of colorectal
      cancer patients.

PMID- 23170118
TI  - Evaluation of the effect of methionine and glucosamine on adjuvant arthritis in
      rats.
AB  - In the present study, we evaluated the effects of individual administration of
      methionine or glucosamine (GlcN) and compared with the combined administration of
      methionine and GlcN on the adjuvant arthritis model of rheumatoid arthritis in
      rats. Adjuvant arthritis was induced in female Lewis rats by injecting Freund's
      complete adjuvant (FCA) into the right hind paws, and methionine (200 mg/kg body
      weight/day) and/or GlcN (400 mg/kg/day) were orally administered for 21 days. The
      progression of the adjuvant arthritis was clinically evaluated for characteristic
      signs and symptoms by employing an arthritis score. The administration of
      methionine combined with GlcN suppressed the swelling of FCA-uninjected left hind
      paws and the arthritis score. Additionally, histopathological examination
      revealed that the combined administration of methionine and GlcN markedly
      suppressed synovial hyperplasia and the destruction of the cartilage surface and
      articular meniscus of the knee joints of FCA-injected right hind paws.
      Furthermore, combined methionine and GlcN administration suppressed the increase
      in the levels of nitric oxide, prostaglandin E(2) and hyaluronic acid in the
      plasma of rats with adjuvant arthritis. By contrast, individual administration of
      methionine or GlcN suppressed arthritis only slightly. These observations suggest
      that the combined administration of methionine and GlcN is more effective
      compared with individual administrations of methionine or GlcN in suppressing the
      progression of adjuvant arthritis (identified as swelling of joints and arthritis
      score), possibly by synergistically inhibiting synovial inflammation (identified
      as synovial hyperplasia and the destruction of the cartilage surface and
      articular meniscus) and the production of inflammatory mediators.

PMID- 23170119
TI  - Protective effects of capillary artemisia polysaccharide on oxidative injury to
      the liver in rats with obstructive jaundice.
AB  - Obstructive jaundice is a condition caused by blockage of the flow of bile out of
      the liver. This results in an overflow of bile and its by-products into the
      blood, and bile excretion from the body is incomplete. Untreated, obstructive
      jaundice can lead to serious infection that spreads to other parts of the body.
      We examined the protective effect of capillary artemisia polysaccharide on
      oxidative damage to the liver in growing rats with obstructive jaundice (OJ).
      Growing male Wistar rats (n=40, age 3-4 weeks) were randomly divided into four
      groups (n=10 in each group): normal control group, sham group, OJ group and OJ
      with capillary artimesia polysaccha-ride treatment group (study group). The rats
      of the OJ group and the study group were subjected to common bile dust ligation,
      while the sham group had the bile duct mobilized but not ligated. The rats of the
      study group recieved 5 ml/kg capillary artimesia polysaccharide (0.5 g/ml) by
      intraperitoneal (i.p.) injection once daily while the other groups were
      administered 5 ml/kg saline by i.p. injection. After 4 weeks, the rats were
      sacrificed to obtain liver weight and to compute the liver coefficient.
      Additional measures included liver homogenate malondialdehyde (MDA) and the
      activity levels of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px)
      and catalase (CAT). The liver weight and liver coefficient of rats in the study
      group were lower than those in the OJ group and higher than those in the control
      and sham groups (P<0.05). Liver homogenate MDA content in the study group rats
      was lower than that in the OJ group and higher than that in the control and sham
      group (P<0.05). SOD, GSH-Px and CAT activities were higher in the study group
      rats than those in the OJ group and lower than those in other groups (P<0.05).
      Capillary artimesia capillary artemisia polysaccharide protects the liver from
      oxidative damage and improves antioxidant defense in growing rats with
      obstructive jaundice.

PMID- 23170120
TI  - Embelin-induced apoptosis of HepG2 human hepatocellular carcinoma cells and
      blockade of HepG2 cells in the G2/M phase via the mitochondrial pathway.
AB  - Embelin is a small-molecule inhibitor extracted from plants of the Myrsinaceae
      family demonstrating specific inhibition of the X-linked inhibitor of apoptosis
      protein (XIAP) to affect the proliferation and apoptosis of various types of
      tumor cells. However, the mechanism of action for this effect remains unclear.
      The purpose of the present study was to investigate the role of the mitochondrial
      pathway in embelin-induced HepG2 human hepatocellular carcinoma cell apoptosis
      and the effect of embelin on the cell cycle. HepG2 human hepatocellular carcinoma
      cells were treated with different doses of embelin. The MTT method was used to
      determine cell viability, and flow cytometry was used to assess the rate of
      apoptosis and the changes in mitochondrial membrane potential; the cell cycle was
      also analyzed. Western blot analysis was performed to determine the expression
      levels of the apoptosis-associated proteins Bax, Bcl-2 and the caspase family.
      The results revealed that embelin induced the apoptosis of the HepG2 cells in a
      dose- and time-dependent manner. In addition, embelin caused changes in
      mitochondrial membrane potential. Flow cytometric analysis demonstrated that
      embelin caused blockade of the HepG2 cells in the G2/M phase of the cell cycle.

PMID- 23170121
TI  - Co-transfection of dendritic cells with AFP and IL-2 genes enhances the induction
      of tumor antigen-specific antitumor immunity.
AB  - Dendritic cells (DCs) are highly efficient, specialized antigen-presenting cells
      and DCs transfected with tumor-related antigens are regarded as promising
      vaccines in cancer immunotherapy. The aim of the present study was to investigate
      whether DCs co-transfected with the alpha-fetoprotein (AFP) and human interleukin
      2 (IL-2) genes were able to induce stronger therapeutic antitumor immunity in
      transfected DCs. In this study, DCs from hepatocellular carcinoma (HCC) patients
      were co-transfected with the IL-2 gene and/or the AFP gene. The reverse
      transcription-PCR (RT-PCR) data revealed that the DCs transfected with the
      adenovirus AdAFP/IL-2 expressed AFP and IL-2. The DCs co-transfected with IL-2
      and AFP (AFP/IL-2-DCs) enhanced the cytotoxicities of cytotoxic T lymphocytes
      (CTLs) and increased the production of IL-2 and interferon-gamma significantly
      compared with their AFP-DC, green fluorescent protein (GFP)-DC, DC or phosphate
      buffered saline (PBS) counterparts. In vivo data suggested that immunization with
      AFP-DCs enhances antigen-specific antitumor efficacy more potently than
      immunization with IL-2-DCs or AFP-DCs. These findings provide a potential
      strategy to improve the efficacy of DC-based tumor vaccines.

PMID- 23170122
TI  - Challenging delivery of VLHL NS plasminogen activator inhibitor-1 by osmotic
      pumps in diabetic mouse: A case report.
AB  - ALZET((r)) osmotic pumps are implantable devices used in animals for the
      continuous infusion of drugs or proteins at controlled rates from 1 day to 4
      weeks. Pumps have been used successfully in a number of studies on the effects of
      controlled delivery of a wide range of experimental agents, independent of their
      properties. In the present study, use of these pumps was made in mice with
      diabetic nephropathy. Plasminogen activator inhibitor-1 (PAI-1) mediates diabetic
      nephropathy, which is characterized by the excessive accumulation of
      extracellular matrix (ECM) in the kidney. Disproportionate PAI-1 inactivates
      tissue plasminogen activator, which is one of the proteolytic enzymes in a
      cascade responsible for ECM remodeling in the kidney. The decrease of PAI-1 in
      the kidney has been shown to arrest the progression of nephropathy in
      experimental animals. This was achieved using inactive PAI-1R which increased the
      clearance of wild-type PAI-1 in order to protect net proteolytic activity and ECM
      clearance. However, this protein has a brief half-life in vivo, therefore, high
      and frequent doses are required. Thus, VLHL NS PAI-1 protein with a long half
      life of over 700 h (Gln197Cys, Gly355Cys) inactivated by single point mutation
      (Arg369Ala) was used. Following the sacrifice of animals the tips of the flow
      moderators of the osmotic pumps in the treated animals were found to be clogged.
      In addition, from each pump from the treatment group, but not controls, we
      collected 50-150 MUl of clear liquid containing VLHL NS PAI-1, cellular and serum
      proteins suggesting early pump sealing by cellular material. In conclusion,
      despite encouraging results obtained for the PAI-1R protein, the method of VLHL
      PAI-1 delivery should be ameliorated.

PMID- 23170123
TI  - Diagnostic accuracy of the International HIV Dementia Scale and HIV Dementia
      Scale: A meta-analysis.
AB  - This aim of this study was to assess the diagnostic accuracy of the International
      HIV Dementia Scale (IHDS) or HIV Dementia Scale (HDS) for the diagnosis of HIV
      associated neurocognitive disorders (HAND). A comprehensive and systematic search
      was carried out in PubMed and EMBASE databases. Sensitivity, specificity, Q(*)
      values, summary receiver operating characteristic curves and other measures of
      accuracy of IHDS or HDS in the diagnosis of HAND were summarized. Summary
      receiver operator characteristic (SROC) curve analysis for HAND data demonstrates
      a pooled sensitivity of 0.90 [95% confidence interval (CI), 0.88-0.91] and
      overall specificity of 0.96 (95% CI, 0.95-0.97) for IHDS, the Q(*)-value for IHDS
      was 0.9195 and the diagnostic odds ratio (DOR) was 162.28 (95% CI, 91.82-286.81).
      HDS had an overall sensitivity of 0.39 (95% CI, 0.34-0.43) and specificity of
      0.90 (95% CI, 0.89-0.91), the Q(*)-value for HDS was 0.6321 and DOR was 5.81 (95%
      CI, 3.64-9.82). There was significant heterogeneity for studies that reported
      IHDS and HDS. This meta-analysis has shown that IHDS and HDS may offer high
      diagnostic performance accuracy for the detection of HAND in primary health care
      and resource-limited settings. IHDS and HDS may require reformed
      neuropsychological characterization of impairments in accordance with regional
      culture and language in future international studies.

PMID- 23170124
TI  - Impact of intense pulsed light irradiation on cultured primary fibroblasts and a
      vascular endothelial cell line.
AB  - The aim of this study was to determine the effects of intense pulsed light (IPL)
      on cell proliferation and the secretion of vascular endothelial growth factor
      (VEGF) and matrix metalloproteinases (MMPs) in human fibroblasts and vascular
      endothelial cell lines, and to investigate the effects of IPL on the mRNA
      expression levels of type I and III procollagens in cultured human fibroblasts.
      Foreskin fibroblasts and a vascular endothelial cell line (ECV034) were cultured
      and treated with various wavelengths and doses of IPL irradiation. After culture
      for 1, 12, 24 and 48 h following IPL irradiation, fibroblasts and the vascular
      endothelial cell line were harvested for investigation of morphological changes
      by light microscopy, cell proliferation viability by MTT assay, and VEGF and MMP
      secretions by ELISA. The mRNA expression levels of type I and III procollagens in
      the fibroblasts were detected by RT-PCR. No marked morphological changes were
      observed in the cultured fibroblasts compared with the control. Cell growth and
      cellular viability were increased in fibroblasts 24 and 48 h after IPL
      irradiation. The levels of type I and III procollagen mRNA expression in
      fibroblasts increased in a time-dependent manner. However, the IPL management had
      no impact on VEGF and MMP secretion levels in fibroblasts and the ECV034 cell
      line at any time-point after irradiation as well as cell morphology and cellular
      proliferation. IPL irradiation may induce cellular proliferation and promote the
      expression of procollagen mRNAs directly in cultured primary fibroblasts, which
      may primarily contribute to photorejuvenation.

PMID- 23170125
TI  - Comparison of subcutaneous central venous port via jugular and subclavian access
      in 347 patients at a single center.
AB  - The purpose of the present study was to examine whether patency times, including
      complications of subcutaneous venous chest port insertion using ultrasonography
      (US) guidance, differ between jugular and subclavian venous access. Between
      December 2008 and July 2010, subcutaneous venous chest ports were placed in 347
      patients by an experienced team. All single-lumen port catheters were placed into
      jugular and subclavian veins under US and fluoroscopy guidance. Patency times and
      complication rates of ports via these routes were compared and the variables were
      age, gender, access, site of malignancy and coagulation parameters. The success
      of the jugular and subclavian groups was compared by univariate Kaplan-Meier
      survival analysis and the multivariable Cox regression test. A total of 15
      patients underwent port removal due to complications. As a rate per 100 catheter
      days, ports were explanted in 7 (0.0092) due to thrombosis, 4 (0.0053) for
      catheter malposition, one each (0.0013) of port reservoir flip-over, bleeding,
      port pocket infection, skin necrosis and incision dehiscence, for a total of 15
      patients (0.0197). Patency times were not different in the jugular and subclavian
      veins. Factors were not significant, with the exception of platelet count. There
      was no significant difference in patency times, including complications, between
      jugular vein access and subclavian vein access using US. This should be
      considered when selecting the access method.

PMID- 23170126
TI  - Effects of low doses of estrone on the proliferation, differentiation and
      mineralization of osteoprecursor cells.
AB  - The purpose of this study was to evaluate the effects of low doses of estrone on
      the proliferation, differentiation and mineralization of osteoprecursor cells.
      The effect on cell viability was determined using a 3-[4,5-dimethylthiazol-2-yl]
      2,5-diphenyltetrazolium bromide (MTT) assay, whereas differentiation and
      mineralization were examined using an alkaline phosphatase activity test and
      alizarin red S staining, respectively. The protein expression of estrogen
      receptor-alpha (ER-alpha), estrogen receptor-beta (ER-beta) and osteopontin (OPN)
      is assosciated with bone formation. Cell cultures grown in the presence of
      estrone at concentrations of 0.1 and 1 nM demonstrated an increase in relative
      values in the MTT assay and cells grown in the presence of estrone at the 10 nM
      concentration demonstrated an increase in mineralization. The results of the
      western blot analysis indicated that the addition of estrone upregulated ER-alpha
      and ER-beta expression, but downregulated the expression of OPN. Based on these
      findings, it was hypothesized that a low dose of estrone produces positive
      effects on the mineralization of osteoprecursor cells. Moreover, these results
      also suggested that higher doses of estrone may be required to significantly
      enhance the differentiation and mineralization.

PMID- 23170127
TI  - Simultaneous transurethral resection of bladder cancer and prostate may reduce
      recurrence rates: A systematic review and meta-analysis.
AB  - The aim of this study was to evaluate the recurrence rate of simultaneous
      transurethral resection of bladder cancer and prostate (TURBT+TURP) in the
      treatment of non-muscle invasive bladder cancer (NMIBC) with benign prostatic
      hyperplasia (BPH). We searched PubMed, the Cochrane Central Register of
      Controlled Trials (CENTRAL), EMBASE and the ISI Web of Knowledge databases from
      their establishment until March 2012, to collect all the original studies on
      TURBT+TURP vs. TURBT alone in the treatment of NMIBC with BPH. After screening
      the literature, methodological quality assessment and data extraction was
      conducted independently by two reviewers and meta-analysis was performed using
      the RevMan 5.1 software. The quality of data was assessed using the Grades of
      Recommendation, Assessment, Development and Evaluation (GRADE) approach. Eight
      studies, including seven non-randomized concurrent controlled trials (NRCCTs) and
      one randomized controlled trial (RCT), involving a total of 1,372 patients met
      the criteria. Meta-analyses of NRCCTs showed that in the TURBT+TURP group,
      overall recurrence rates were lower [odds ratio (OR), 0.76; 95% confidence
      interval (CI), 0.60-0.96; P=0.02] and the difference was statistically
      significant. The postoperative recurrence rate in the prostatic fossa/bladder
      neck (OR, 0.96; 95% CI, 0.64-1.45; P=0.86) and bladder tumor progression rates
      (OR, 0.96; 95% CI, 0.49-1.87; P=0.91) were similar between the TURBT+TURP and
      TURBT groups, but the difference was not significant. According to the GRADE
      approach, the level of evidence was moderate or low. Only one RCT demonstrated
      that overall postoperative tumor recurrence rates, recurrence rates at prostate
      fossa/bladder neck and bladder tumor progression rates between simultaneous
      groups and control groups were almost equal. There was no significant difference
      (P>0.05), and the level of evidence was moderate. For patients with NMIBC and
      BPH, simultaneous resection did not increase the overall recurrence rate of
      bladder tumors, it also did not cause metastasis and tumor progression, but it
      may reduce the recurrence rate. However, due to the low quality of investigations
      included in the present study, careful selection was necessary, and more large
      scale and high-quality randomized controlled trials are also required for further
      confirmation.

PMID- 23170128
TI  - Clinical impact of (18)F-FDG PET/CT on initial staging and therapy planning for
      breast cancer.
AB  - The purpose of this study was to determine the clinical significance of (18)F-FDG
      PET/CT on initial staging and therapy planning in patients with invasive breast
      cancer. One hundred and forty-one consecutive, biopsy proven preoperative and 195
      postoperative high-risk breast cancer patients who were referred for PET/CT for
      initial staging were included in this retrospective study. The clinical stage had
      been determined by conventional imaging modalities prior to the PET/CT scan. Of
      the 141 examined preoperative patients, 19 had clinical stage I (T1N0), 51 had
      stage IIA (12 T2N0 and 39 T1N1), 49 had stage IIB (2 T3N0 and 47 T2N1), 12 had
      stage IIIA (11 T3N1, 1 T2N2), 2 had stage IIIB (2 T4N1) and 8 had stage IV.
      PET/CT modified the staging for 26% of stage I patients, 29% of stage IIA
      patients, 46% of stage IIB patients, 58% of stage IIIA patients and 100% of stage
      IIIB patients. PET/CT scans detected extra-axillary regional lymph nodes in 14
      (9.9%) patients and distant metastasis in 41 (29%) patients. PET/CT scans
      detected multifocal lesions in 30 (21%) patients, multicentric lesions in 21
      (14%) patients and malign foci in the contralateral breast (bilateral breast
      cancer) confirmed by biopsy in 5 (3.5%) patients. Of the examined 195
      postoperative patients PET/CT detected axillary lymph nodes in 22 (11%) patients,
      extra-axillary regional lymph nodes in 21 (10%) patients and distant metastasis
      in 24 (12%) patients. PET/CT findings altered plans for radiotherapy in 22 (11%)
      patients and chemotherapy was adapted to the meta-static diseases in 24 (12%)
      patients. PET/CT was revealed to be superior to conventional imaging modalities
      for the detection of extra-axillary regional metastatic lymph nodes and distant
      metastases. These features make PET/CT an essential imaging modality for the
      primary staging of invasive breast cancer, particularly in patients with clinical
      stages II and III.

PMID- 23170129
TI  - Red clover extract exerts antidiabetic and hypolipidemic effects in db/db mice.
AB  - To investigate the effects of red clover extract on the blood glucose and lipid
      levels of type 2 diabetic db/db mice, male db/db mice were treated with this
      extract for a period of 5 weeks. The red clover extract had a significant effect
      on lowering the blood glucose levels of db/db mice. The serum triglyceride, serum
      total cholesterol, liver triglyceride and liver cholesterol levels for diabetic
      mice receiving red clover extract were significantly lower compared to those of
      the untreated diabetic mice. The mRNA expression of two target genes
      transcriptionally regulated by peroxisome proliferator-activated receptor
      (PPAR)gamma was determined by quantitative real-time RT-PCR, and red clover
      extract was observed to significantly upregulate hepatic glucokinase and CD36
      expression. Four target genes transcriptionally regulated by PPARalpha were also
      assayed, and red clover extract was observed to significantly downregulate
      hepatic apolipoprotein C3 expression whereas it had no significant effect on
      apolipoprotein A5, acetyl CoA oxidase and carnitine palmitoyl transferase-1
      expression. In addition, hepatic mRNA expression of fatty acid synthase was also
      observed to be downregulated by red clover extract treatment. Thus, we conclude
      that red clover extract significantly improves the glucose and lipid homeostasis
      in db/db diabetic mice and that these effects are achieved at least in part by
      activating hepatic PPARalpha/gamma and by inhibiting hepatic fatty acid synthase.

PMID- 23170130
TI  - Detection of active P-glycoprotein in systemic lupus erythematosus patients with
      poor disease control.
AB  - Active P-glycoprotein (P-gp) molecules have been shown to transport steroids out
      of peripheral lymphocytes, resulting in poor responses to systemic steroid
      therapy in patients with systemic lupus erythematosus (SLE). This study was
      carried out to investigate the correlation between the expression or activity of
      P-gp in peripheral lymphocytes and disease control in SLE patients with a long
      history of systemic steroid treatment. A total of 60 SLE patients who had
      received systemic steroid treatment for longer than 6 months and 30 healthy
      subjects were monitored. SLE patients were subclassified into those with active
      and severely active forms of the disease according to their disease activity
      (estimated by SLEDAI-2000). The expression levels and activity of P-gp in
      peripheral blood lymphocytes were determined. Lymphocytes, obtained from three
      patients with severely active SLE, with high levels of P-gp expression were
      treated with cyclophosphamide, mycophenolic acid or emodin in vitro and Rh123
      efflux activity was measured. P-gp expression in the peripheral lymphocytes of
      the SLE patients was significantly higher compared with that of the healthy
      controls, and a positive correlation between disease activity and P-gp expression
      levels was observed in these 60 patients. A significant increase in P-gp
      expression was observed in the severely active compared with the active SLE
      group. Treatment of lymphocytes with 100 MUM cyclophosphamide or 100 MUM emodin
      in vitro induced up to a 2-fold increase in the mean fluorescence intensity, as
      detected by the Rh123-efflux assay. In conclusion, the high expression levels of
      P-gp in the peripheral lymphocytes of SLE patients leads to poor disease control
      by systemic steroids. Emodin, an active ingredient derived from Chinese herbs,
      possesses a promising effect for overcoming P-gp-mediated steroid resistance by
      inhibiting the P-gp efflux function.

PMID- 23170131
TI  - Comparison of the characteristics of mesenchymal stem cells obtained from
      prostate tumors and from bone marrow cultured in conditioned medium.
AB  - Prostate cancer (PCa) is the most common type of cancer worldwide. Mesenchymal
      stem cells (MSCs) can also be utilized as 'tumor stromal cells', which are
      associated with invasive and metastatic malignant tumor cells. Our study aimed to
      investigate MSCs in prostate tumors and normal MSCs and evaluate their
      differential characteristics. Normal MSCs (BMMSCs) were isolated from the femur
      and tibia of normal mice; prostate tumor MSCs (PCa-MSCs) were obtained from
      prostate tumors implanted in mice. These two types of MSCs were induced to
      differentiate into adipocytes, bone cells and chondrocytes. Growth curves were
      used to analyze the growth ability of PCa-MSCs and BMMSCs. Tritium-labeled
      thymidine (3H-TdR) was used to evaluate cell proliferation of RM-1 stimulated by
      MSCs. The time taken for PCa-MSCs to reach 90% confluence was markedly shorter
      than that of BMMSCs (8-10 vs. 12-14 days). The differentiation ability of PCa
      MSCs was similar to that described in previous reports. The growth ability of PCa
      MSCs was significantly higher than that of BMMSCs. The proliferative activity of
      PCa-MSCs was also higher than that of BMMSCs. Our data showed that PCa-MSCs
      exhibit identical characteristics when compared with those of MSCs. Additionally,
      their proliferative activity and growth ability were significantly higher when
      compared with these values in BMMSCs, which appear to have an intrinsic, cell
      specific capacity to localize to PCa. The possible role of PCa-MSCs in the
      process of PCa development requires further clarification.

PMID- 23170132
TI  - Effect of NF-kappaB inhibitors on the chemotherapy-induced apoptosis of the colon
      cancer cell line HT-29.
AB  - This study aimed to investigate the impact of the combined use of the nuclear
      factor-kappaB (NF-kappaB) inhibitors pyrrolidine dithiocarbamate (PDTC),
      bortezomib or SN50, and the chemotherapy agents arsenic acid (As(2)O(3)),
      fluorouracil (5FU), oxaliplatin or paclitaxel on the growth and apoptosis of HT
      29 cells. Cell morphology was observed using inverted microscopy, and cell
      viability and apoptosis were assessed using the MTT assay and flow cytometry,
      respectively. The activities of NF-kappaB were analyzed by western blotting and
      electrophoretic mobility shift assay (EMSA). Cell growth was significantly
      inhibited by As(2)O(3), oxaliplatin and paclitaxel in a time- and concentration
      dependent manner (P<0.05), while 5FU inhibited cell growth in a time-dependent
      manner only (P<0.05). The growth inhibition rate and apoptosis induction ratio
      were increased following the combined treatment of the chemotherapy agent and NF
      kappaB inhibitor. The expression of NF-kappaB p65 was upregulated when cells were
      treated with a chemotherapy drug, however it was downregulated following combined
      treatment or treatment with an NF-kappaB inhibitor alone. In conclusion, an NF
      kappaB inhibitor combined with a chemotherapy drug effectively inhibited cell
      proliferation, induced cell apoptosis and inhibited NF-kappaB activity to enhance
      the chemotherapeutic sensitivity of HT-29 cells.

PMID- 23170133
TI  - Complement factor C5a and C5a receptor contribute to morphine tolerance and
      withdrawal-induced hyperalgesia in rats.
AB  - Morphine is a potent opioid analgesic. However, the repeated use of morphine
      causes tolerance and hyperalgesia. Neuroinflammation has been reported to be
      involved in morphine tolerance and withdrawal-induced hyperalgesia. The
      complement system is a crucial effector mechanism of immune responses. The
      present study investigated the roles of complement factor C5a and C5a receptor
      (C5aR) in the development of morphine tolerance and withdrawal-induced
      hyperalgesia. In the present study, the levels of C5a and C5aR were increased in
      the L5 lumbar spinal cords of morphine-tolerant rats. The administration of C5a
      promoted the development of hyperalgesia and the expression of spinal
      antinociceptive tolerance to intrathecal morphine in both mechanical and thermal
      test. However, these phenomena caused by morphine were significantly attenuated
      by the C5aR antagonist PMX53. These results suggest that complement activation
      within the spinal cord is involved in morphine tolerance and withdrawal-induced
      hyperalgesia. C5a and C5aR may serve as novel targets for the control of morphine
      tolerance and withdrawal-induced hyperalgesia.

PMID- 23170134
TI  - The -149C>T polymorphism of DNMT3B is not associated with colorectal cancer risk:
      Evidence from a meta-analysis based on case-control studies.
AB  - The aim of this study was to examine the association between the -149C>T
      polymorphism of DNA methyltransferase 3B (DNMT3B) and colorectal cancer (CRC)
      susceptibility. A comprehensive search was conducted to identify all case-control
      studies of the -149C>T polymorphism of DNMT3B and CRC risk. Statistical analysis
      was performed with the software program Stata (version 12.0) and Review Manager
      (version 5.0). A total of seven eligible studies, including 2,666 cases and 4,022
      controls, associating the DNMT3B polymorphism of -149C>T with the risk of CRC
      were identified. These studies suggested no significant associations between the 
      149C>T polymorphism of the DNMT3B gene and the risk of developing CRC in the
      recessive, dominant and co-dominant models [for CC vs. TT: odds ratio (OR), 0.90;
      95% confidence interval (CI), 0.90-1.25; P=0.37; for the recessive model: OR,
      0.54, 95% CI, 0.28-1.04; P<0.00001; for the dominant model: OR, 1.07; 95% CI,
      0.93-1.23; P=0.83 and C allele vs. T allele: OR, 0.70; 95% CI, 0.43-1.13;
      P<0.00001]. In the subgroup analysis, no significant associations were found in
      the European populations (for CC vs. TT: OR, 1.09; 95% CI, 0.92-1.30; P=0.88; for
      the recessive model: OR, 1.00; 95% CI, 0.88-1.13; P=0.14; for the dominant model:
      OR, 1.50; 95% CI, 0.89-2.54; P<0.00001 and C allele vs. T allele: OR, 0.70; 95%
      CI, 0.38-1.28; P<0.00001). No significant association was found between the 
      149C>T polymorphism in DNMT3B and CRC susceptibility.

PMID- 23170135
TI  - Detection of benign proliferative lesions on vocal cords with voice handicap
      index.
AB  - The aim of this study was to investigate the significance and practical
      applicability of the voice handicap index (VHI) in the diagnosis of benign
      proliferative lesions of the vocal cords (BLVCs). The detection of VHI included
      the calculation of functional (F), physical (P) and emotional (E) domains, and
      the score of each domain and total score (TVH). The VHI was scored in patients
      with BLVCs and healthy controls. Eighty-four patients with BLVCs and 27 healthy
      controls were enrolled in the present study. The F, P, E and TVH scores were
      10.40+/-7.84, 19.88+/-8.81, 9.39+/-8.49 and 39.37+/-21.83, respectively, in the
      BLVC group and 0.78+/-0.97, 0.85+/-1.06, 0.26+/-0.72 and 1.89+/-2.31,
      respectively, in the control group. A significant difference was found between
      the two groups (P<0. 01). The daily duration of speech and course of BLVCs did
      not correlate with the VHI score in BLVC patients (P>0.05). There was no marked
      difference in the VHI score between voice-consuming and non-voice consuming
      occupations (P>0.05) or between males and females (P>0.05). In BLVC patients, VHI
      may subjectively express the voice handicap, while daily duration of speech,
      course of BLVC, occupation and gender have no impact on VHI.

PMID- 23170136
TI  - The membrane-cytoskeletal protein 4.1N is involved in the process of cell
      adhesion, migration and invasion of breast cancer cells.
AB  - Protein 4.1N belongs to the protein 4.1 superfamily that links transmembrane
      proteins to the actin cytoskeleton. Recent evidence has shown that protein 4.1 is
      important in tumor suppression. However, the functions of 4.1N in the metastasis
      of breast cancer are largely unknown. In the present study, MCF-7, T-47D and MDA
      MB-231 breast cancer cell lines with various metastatic abilities were employed.
      Protein 4.1N was found to be expressed in poorly metastatic MCF-7 and middle
      metastatic T-47D cell lines, and was predominantly associated with cell-cell
      junctions. However, no 4.1N expression was detected in the highly metastatic MDA
      MB-231 cells. Moreover, re-expression of 4.1N in MDA-MB-231 cells inhibited cell
      adhesion, migration and invasion. The results suggest that protein 4.1N is a
      negative regulator of cell metastasis in breast cancer.

PMID- 23170137
TI  - Association of angiotensin-converting enzyme gene I/D and CYP11B2 gene -344T/C
      polymorphisms with lone atrial fibrillation and its recurrence after catheter
      ablation.
AB  - The renin-angiotensin-aldosterone system (RAAS) plays a key role in atrial
      structural and electrical remodeling. The aim of this study was to investigate
      the potential associations of angiotensin-converting enzyme (ACE) gene insertion/
      deletion (I/D) and aldosterone synthase (CYP11B2) gene -344T/C polymorphisms with
      the risk and recurrence of lone atrial fibrillation (AF). One hundred and ninety
      three patients who underwent successful catheter ablation for lone AF were
      recruited. Two hundred and ninety-seven sinus rhythm subjects without a history
      of arrhythmia served as controls. The subjects were genotyped for ACE gene I/D
      and CYP11B2 gene -344T/C polymorphisms. Results showed that the ACE gene DD
      genotype and D allele were associated with a greater prevalence of lone AF (both
      P<0.01). In addition, the ACE gene DD genotype had a significantly larger left
      atrial dimension (LAD; 41.6+/-5.7 mm vs. 39.6+/-5.2 mm; P=0.043) and higher risk
      of AF recurrence [44.7% vs. 23.2%; odds ratio (OR), 2.68; 95% confidence interval
      (CI), 1.28-5.61; P=0.008] compared with the II+ID genotype in lone AF patients.
      After adjustment for a variety of risk factors, the ACE gene DD genotype had a
      1.97-fold increased risk for lone AF (OR, 1.97; 95% CI, 1.15-3.37; P= 0.013) and
      2.35-fold increased risk for AF recurrence (RR, 2.35; 95% CI, 1.10-5.04; P=0.028)
      compared with the ACE gene II+ID genotype. However, no correlation between the
      CYP11B2 gene -344T/C polymorphism and lone AF or its recurrence was observed in
      this cohort. In conclusion, the ACE gene DD genotype was associated with an
      increased incidence of lone AF and its recurrence following ablation, which was
      partly mediated by LAD.

PMID- 23170138
TI  - Lack of association of the cyclin D1 G870A variation with oral carcinoma risk:
      Evidence from 2,404 subjects.
AB  - Evidence implicates cyclin D1 (CCND1) G870A polymorphisms as risk factors for
      various cancers. An increasing number of investigations have been conducted on
      the association of CCND1 G870A polymorphisms with susceptibility to oral
      carcinoma, and have yielded inconclusive results. The aim of the present study
      was to derive a more precise estimation of the correlation. Meta-analyses
      examining the association between CCND1 G870A polymorphisms and oral carcinoma
      were performed. Separate analyses on ethnicity, smoking status and control
      sources were also implemented. Eligible studies were identified prior to February
      2012. From the overall data from 1,128 cases and 1,276 controls, no associations
      of CCND1 G870A polymorphisms with oral carcinoma were observed [AA vs. GG: odds
      ratio (OR)=1.06; 95% confidence interval (CI), 0.62-1.82; dominant model:
      OR=1.04; 95% CI, 0.76-1.43; recessive model: OR=1.06; 95% CI, 0.70-1.59]. In the
      subgroup analysis by ethnicity, smoking status and control sources, no
      significant associations of CCND1 G870A polymorphisms and oral cancer were
      observed for the three genetic models. Collectively, the data failed to suggest
      CCND1 G870A polymorphism as a low-penetrant risk factor for developing oral
      carcinoma. Additional studies with large sample sizes concerning different
      ethnicities in different areas are required.

PMID- 23170140
TI  - CASP-8 -652 6N ins/del polymorphism and cancer risk: A literature-based
      systematic HuGE review and meta-analysis.
AB  - Caspase-8 (encoded by the CASP-8 gene) is crucial in generating cell death
      signals and eliminating potentially malignant cells. Genetic variation in CASP8
      may affect susceptibility to cancer. The CASP-8 -652 6N ins/del (rs3834129)
      polymorphism has been previously reported to influence the progression to several
      cancers. However, the overall reported studies have shown inconsistent
      conclusions. In this human genome epidemiology (HuGE) review and meta-analysis,
      the aim was to identify the association between CASP-8 -652 6N ins/del
      polymorphism and cancer risk. According to the inclusion criteria, 19 case
      control studies with a total of 23,172 cancer cases and 26,532 healthy controls
      were retrieved. Meta-analysis results showed that the del allele, del allele
      carrier and ins/del genotype of -652 6N ins/del in the CASP-8 gene were
      negatively associated with cancer risk (OR=0.91, 95% CI=0.84-0.98, P=0.01;
      OR=0.88, 95% CI=0.80-0.96, P=0.005; OR=0.91, 95% CI=0.85-0.98, P<0.001;
      respectively, while no significant correlation was observed between the del/del
      genotype of -652 6N ins/del and cancer risk (OR=0.89, 95% CI=0.79-1.01, P=0.08).
      In the subgroup analysis by ethnicity, the meta-analysis indicated that Caucasian
      populations harboring the del allele, del allele carriers and ins/del genotype
      had a lower cancer risk (OR=0.96, 95% CI=0.93-1.00, P=0.05; OR=0.86, 95% CI=0.75
      1.00, P=0.05; OR=0.91, 95% CI=0.84-0.98, P=0.01; respectively). In addition, a
      negative association was found between the del allele of -652 6N ins/del in the
      CASP-8 gene and cancer risk in the Asian population (OR=0.89, 95% CI=0.83-0.97,
      P=0.005). In conclusion, this meta-analysis suggests that the del allele, del
      allele carrier and ins/del geno-type of the -652 6N ins/del polymorphism in the
      CASP-8 gene may be protective factors for cancer risk.

PMID- 23170139
TI  - Effects of siRNA-mediated knockdown of jumonji domain containing 2A on
      proliferation, migration and invasion of the human breast cancer cell line MCF-7.
AB  - Jumonji domain containing 2A (JMJD2A) is a potential cancer-associated gene that
      may be involved in human breast cancer. The present study aimed to investigate
      suppressive effects on the MCF-7 human breast cancer cell line by transfection
      with JMJD2A-specific siRNA. Quantitative real-time PCR and western blot analysis
      were used to detect the expression levels of JMJD2A. Flow cytometric (FCM)
      analysis and WST-8 assay were used to evaluate cell proliferation. Boyden
      chambers were used in cell migration and invasion assays to evaluate the cell
      exercise capacity. Expression levels of JMJD2A mRNA and protein in the siRNA
      group were both downregulated successfully by transfection. FCM results showed
      that the percentage of cells in the G0/G1 phase in the siRNA group was
      significantly greater than that in the blank (P<0.05) and negative control groups
      (P<0.05). Additionally, the mean absorbance in the siRNA group was significantly
      lower (P<0.05), as observed by WST-8 assay. Moreover, a decreased number of
      migrated cells in the siRNA group was observed (P<0.05) using a cell migration
      and invasion assay. These data indicated that knockdown of JMJD2A may cause
      inhibition of proliferation, migration and invasion of MCF-7 cells. This study
      provides a new perspective in understanding the molecular mechanisms underlying
      the progression of breast cancer and offers a potential therapeutic target for
      breast cancer.

PMID- 23170141
TI  - Endoscopic ultrasound in gastroenteropancreatic neuroendocrine tumors.
AB  - Endoscopic ultrasound (EUS) is an advanced endoscopic technique currently used in
      the staging and diagnosis of many gastrointestinal neoplasms. The proximity of
      the echoendoscope to the gastrointestinal tract lends itself to a detailed view
      of the luminal pathology and the pancreas. This unique ability enables
      endoscopists to use EUS in patients with gastroenteropancreatic neuroendocrine
      tumors (GEP-NETs). Diagnostic EUS allows previously unidentified NETs to be
      localized. EUS also determines tumor management by staging the GEP-NETS, enabling
      the clinicians to choose the appropriate endoscopic or surgical management. The
      ability to obtain a tissue diagnosis with EUS guidance enables disease
      confirmation. Finally, recent developments suggest that EUS may be used to
      deliver therapeutic agents for the treatment of NETs. This review will highlight
      the advances in our knowledge of EUS in the clinical management of these tumors.

PMID- 23170142
TI  - Dietary Factors: Major Regulators of the Gut's Microbiota.
AB  - Dietary factors and the associated lifestyle play a major role in the
      pathophysiology of many diseases. Several diets, especially a Western lifestyle
      with a high consumption of meat and carbohydrates and a low consumption of
      vegetables, have been linked to common diseases, such as metabolic syndrome,
      atherosclerosis, inflammatory bowel diseases, and colon cancer. The
      gastrointestinal tract harbors a complex and yet mainly molecularly defined
      microbiota, which contains an enormous number of different species. Recent
      advances in sequencing technologies have allowed the characterization of the
      human microbiome and opened the possibility to study the effect of
      "environmental" factors on this microbiome. The most important environmental
      factor is probably "what we eat," and the initial studies have revealed
      fascinating results on the interaction of nutrients with our microbiota. Whereas
      short-term changes in dietary patterns may not have major influences, long-term
      diets can affect the microbiota in a substantial manner. This issue may
      potentially have major relevance for human gastrointestinal health and disease
      because our microbiota has features to regulate many immune and metabolic
      functions. Increasing our knowledge on the interaction between nutrients and
      microbiota may have tremendous consequences and result in a better understanding
      of diseases, even beyond the gastrointestinal tract, and finally lead to better
      preventive and therapeutic strategies.

PMID- 23170143
TI  - Role of janus kinase/signal transducers and activators of transcription in the
      pathogenesis of pancreatitis and pancreatic cancer.
AB  - In the pathogenesis of pancreatitis, oxidative stress is involved in the
      activation of the Janus kinase/signal transducer and activator of transcription
      (JAK/STAT) pathway and cytokine expression. High serum levels of cholecystokinin
      (CCK) have been reported in patients with acute pancreatitis, and treatment with
      cerulein, a CCK analogue, induces acute pancreatitis in a rodent model. Recent
      studies have shown that cerulein-activated nicotinamide adenine dinucleotide
      phosphate oxidase elicits reactive oxygen species, which trigger the
      phosphorylation of the JAK1, STAT1, and STAT3 proteins and induce the production
      of inflammatory cytokines, such as tumor necrosis factor-alpha, interleukin (IL)
      1beta, and IL-6, in pancreatic acinar cells. The JAK/STAT pathway also stimulates
      cell proliferation and malignant transformation and inhibits apoptosis in the
      pancreas. This review discusses the possible role of the JAK/STAT pathway in the
      pathogenesis of pancreatitis and pancreatic cancer in response to oxidative
      stress.

PMID- 23170144
TI  - Characteristics of hemorrhagic peptic ulcers in patients receiving
      antithrombotic/nonsteroidal antiinflammatory drug therapy.
AB  - BACKGROUND/AIMS: Antithrombotic/nonsteroidal antiinflammatory drug (NSAID)
      therapies increase the incidence of upper gastrointestinal bleeding. The features
      of hemorrhagic peptic ulcer disease in patients receiving antithrombotic/NSAID
      therapies were investigated. METHODS: We investigated the medical records of 485
      consecutive patients who underwent esophagogastroduodenoscopy and were diagnosed
      with hemorrhagic gastroduodenal ulcers. The patients treated with antithrombotic
      agents/NSAIDs were categorized as the antithrombotic therapy (AT) group (n=213).
      The patients who were not treated with antithrombotics/NSAIDs were categorized as
      the control (C) group (n=263). The clinical characteristics were compared between
      the groups. RESULTS: The patients in the AT group were significantly older than
      those in the C group (p<0.0001). The hemoglobin levels before/without transfusion
      were significantly lower in the AT group (8.24+/-2.41 g/dL) than in the C group
      (9.44+/-2.95 g/dL) (p<0.0001). After adjusting for age, the difference in the
      hemoglobin levels between the two groups remained significant (p=0.0334). The
      transfusion rates were significantly higher in the AT group than in the C group
      (p=0.0002). However, the outcome of endoscopic hemostasis was similar in the AT
      and C groups. CONCLUSIONS: Patients with hemorrhagic peptic ulcers receiving
      antithrombotic/NSAID therapies were exposed to a greater risk of severe bleeding
      that required transfusion but were still treatable by endoscopy.

PMID- 23170145
TI  - Adsorptive granulocyte/monocyte apheresis for the maintenance of remission in
      patients with ulcerative colitis: a prospective randomized, double blind, sham
      controlled clinical trial.
AB  - BACKGROUND/AIMS: Weekly granulocyte/monocyte adsorption (GMA) to deplete elevated
      and activated leucocytes should serve as a non-pharmacological intervention to
      induce remission in patients with ulcerative colitis (UC). This trial assessed
      the efficacy of monthly GMA as a maintenance therapy to suppress UC relapse.
      METHODS: Thirty-three corticosteroid refractory patients with active UC received
      10 weekly GMA sessions as a remission induction therapy. They were then
      randomized to receive one GMA session every 4 weeks (True, n=11), extracorporeal
      circulation without the GMA column every 4 weeks (Sham, n=11), or no additional
      intervention (Control, n=11). The primary endpoint was the rate of avoiding
      relapse (AR) over 48 weeks. RESULTS: At week 48, the AR rates in the True, Sham,
      and Control groups were 40.0%, 9.1%, and 18.2%, respectively. All patients were
      steroid-free, but no statistically significant difference was seen among the
      three arms. However, in patients who could taper their prednisolone dose to <20
      mg/day during the remission induction therapy, the AR in the True group was
      better than in the Sham (p<0.03) or Control (p<0.05) groups. CONCLUSIONS: Monthly
      GMA may potentially prevent UC relapse in patients who have achieved remission
      through weekly GMA, especially in patients on <20 mg/day PSL at the start of the
      maintenance therapy.

PMID- 23170146
TI  - Comparison of the Eradication Rate between 1- and 2-Week Bismuth-Containing
      Quadruple Rescue Therapies for Helicobacter pylori Eradication.
AB  - BACKGROUND/AIMS: First-line therapies against Helicobacter pylori, including
      proton pump inhibitors (PPIs) plus two antibiotics, may fail in up to 20% of
      patients. 'Rescue' therapy is usually needed for patients who failed the first
      line treatment. This study evaluated the eradication rate of bismuth-containing
      quadruple rescue therapy over a 1- or 2-week period. METHODS: We prospectively
      investigated 169 patients with a persistent H. pylori infection after the first
      line triple therapy, which was administered from October 2008 to March 2010. The
      patients were randomized to receive a 1- or 2-week quadruple rescue therapy
      (pantoprazole 40 mg b.i.d., tripotassium dicitrate bismuthate 300 mg q.i.d.,
      metronidazole 500 mg t.i.d., and tetracycline 500 mg q.i.d.). After the 'rescue'
      therapy, the eradication rate, compliance, and adverse events were evaluated.
      RESULTS: The 1-week group achieved 83.5% (71/85) and 87.7% (71/81) eradication
      rates in the intention to treat (ITT) and per-protocol (PP) analyses,
      respectively. The 2-week group obtained 87.7% (72/84) and 88.9% (72/81)
      eradication rate in the ITT and PP analyses, respectively. There was no
      significant difference in the eradication rate, patient compliance or rate of
      adverse events between the two groups. CONCLUSIONS: One-week bismuth-containing
      quadruple therapy can be as effective as a 2-week therapy after the failure of
      the first-line eradication therapy.

PMID- 23170147
TI  - Impaired esophageal bolus transit in patients with gastroesophageal reflux
      disease and abnormal esophageal Acid exposure.
AB  - BACKGROUND/AIMS: We assessed the bolus transit and motility characteristics in
      gastroesophageal reflux disease (GERD) patients with abnormal esophageal pH
      monitoring. METHODS: We retrospectively reviewed the combined impedance
      esophageal manometry data from consecutive patients who had abnormal acid
      exposure during 24-hour esophageal pH monitoring. We compared these data to the
      results from functional heartburn (FH) and asymptomatic volunteers. RESULTS: The
      data from 33 GERD patients (mean age of 51 years, 18 males), 14 FH patients (mean
      age of 51 years, one male), and 20 asymptomatic volunteers (mean age of 27 years,
      nine males) were analyzed. Ineffective esophageal motility was diagnosed in 10%
      of the volunteers, 21% of the FH patients, and 15% of the GERD patients.
      Ineffective contraction was more frequent in GERD and FH patients than in
      volunteers (16% and 20% vs 6%, respectively; p<0.05). Additionally, 10% of the
      volunteers, 21% of the FH patients and 36% of the GERD patients had an abnormal
      bolus transit. Complete bolus transit was less frequent, and bolus transit was
      slower in GERD patients than in volunteers for liquid (70% vs 85%) and viscous
      swallows (57% vs 73%). A longer acid clearance time was associated with abnormal
      bolus transit in the GERD group. CONCLUSIONS: Patients with GERD have mild
      peristaltic dysfunction and incomplete and slower esophageal bolus transit. These
      conditions predispose them to prolonged acid contact with the esophagus.

PMID- 23170148
TI  - Is endoscopic mucosal resection a sufficient treatment for low-grade gastric
      epithelial dysplasia?
AB  - BACKGROUND/AIMS: The rate of diagnosis of gastric adenoma has increased because
      esophagogastroduodenoscopy is being performed at an increasingly greater
      frequency. However, there are no treatment guidelines for low-grade dysplasia
      (LGD). To determine the appropriate treatment for LGD, we evaluated the risk
      factors associated with the categorical upgrade from LGD to high grade dysplasia
      (HGD)/early gastric cancer (EGC) and the risk factors for recurrence after
      endoscopic treatment. METHODS: We compared the complication rates, recurrence
      rates, and remnant lesions in 196 and 56 patients treated with endoscopic
      submucosal dissection (ESD) and endoscopic mucosal resection (EMR), respectively,
      by histologically confi rming low-grade gastric epithelial dysplasia. RESULTS:
      The en bloc resection rate was significantly lower in the EMR group (31.1%)
      compared with the ESD group (75.0%) (p<0.001). However, no significant difference
      was observed in the prevalence of remnant lesions or recurrence rate (p=0.911) of
      gastric adenoma. The progression of LGD to HGD or EGC caused an increase in the
      incidence of tumor lesions >1 cm with surface redness and depressions.
      CONCLUSIONS: For the treatment of LGD, EMR resulted in a higher incidence of
      uncertain resection margins and a lower en bloc resection rate than ESD. However,
      there was no signifi cant difference in recurrence rate.

PMID- 23170149
TI  - Rifaximin Plus Levofloxacin-Based Rescue Regimen for the Eradication of
      Helicobacter pylori.
AB  - BACKGROUND/AIMS: This study assessed the efficacy of a rifaximin plus
      levofloxacin-based rescue regimen in patients that had failed both triple and
      quadruple standard regimens for the eradication of Helicobacter pylori. METHODS:
      We treated patients for H. pylori between August 2009 and April 2011. The triple
      regimen consisted of combined treatment with amoxicillin, clarithromycin, and
      pantoprazole for 1 week. For failed cases, a quadruple regimen of tetracycline,
      metronidazole, bismuth dicitrate, and lansoprazole for 1 week was administered.
      The rescue regimen for persistently refractory cases was rifaximin 200 mg t.i.d.,
      levofloxacin 500 mg q.d., and lansoprazole 15 mg b.i.d. for 1 week. RESULTS: In
      total, 482 patients were enrolled in this study. The eradication rates associated
      with the first and second regimens were 58% and 60%, respectively. Forty-seven
      out of 58 patients who failed with the second-line regimen received rifaximin
      plus levofloxacin-based third-line therapy. The eradication rate for the third
      regimen was 65%. The cumulative eradication rates were 58%, 85%, and 96% for each
      regimen, respectively. CONCLUSIONS: A rifaximin plus levofloxacin-based regimen
      could be an alternative rescue therapy in patients with resistance to both triple
      and quadruple regimens for the eradication of H. pylori.

PMID- 23170150
TI  - The Performance of Multiple Transgastric Procedures Using the Natural Orifice
      Transluminal Endoscopic Surgery Technique: Is Pure NOTES Satisfactory?
AB  - BACKGROUND/AIMS: Although several groups have demonstrated the usefulness of
      natural orifice transluminal endoscopic surgery (NOTES), there is still concern
      about frequent serious adverse events. We performed this study to determine the
      technical feasibility and safety of pure NOTES with a transgastric approach in a
      porcine model from the endoscopist's point of view. METHODS: Diagnostic
      peritoneoscopy, liver biopsy, salpingo-oophorectomy, and Fallopian tube ligation
      with a transgastric approach using a two-channel therapeutic endoscope were
      performed in 10 healthy female minipigs. These procedures were performed in two
      acute models and eight survival models in consecutive order. RESULTS: The
      technical success rate was 100% for peritoneoscopy (10/10), liver biopsy (5/5),
      salpingo-oophorectomy (10/10), and Fallopian tube ligation (10/10). Eight cases
      of adverse events occurred, including one case of splenic injury, one case of
      bleeding after liver biopsy, two cases of small bowel adhesion after salpingo
      oophorectomy, two cases of hematoma at the salphingo-oophorectomy site, and two
      cases of partial dehiscence at the gastric closure site. The gastric puncture
      site was closed with seven to eight hemoclips in four cases and two hemoclips and
      an endoloop in four cases. CONCLUSIONS: The use of pure NOTES for peritoneoscopy,
      liver biopsy, salpingo-oophorectomy, and Fallopian tube ligation may be
      technically feasible, but considerable adverse events can occur during or after
      the procedure. Further studies utilizing specialized techniques overcome several
      limitations of pure NOTES are therefore necessary.

PMID- 23170151
TI  - Safety and efficacy of deep sedation with propofol alone or combined with
      midazolam administrated by nonanesthesiologist for gastric endoscopic submucosal
      dissection.
AB  - BACKGROUND/AIMS: Endoscopic submucosal dissection (ESD) is accepted as a
      treatment for gastric neoplasms and usually requires deep sedation. The aim of
      this study was to evaluate the safety and efficacy profiles of deep sedation
      induced by continuous propofol infusion with or without midazolam during ESD.
      METHODS: A total of 135 patients scheduled for ESDs between December 2008 and
      June 2010 were included in this prospective study and were randomly assigned to
      one of two groups: the propofol group or the combination group (propofol plus
      midazolam). RESULTS: The propofol group reported only one case of severe
      hypoxemia with no need of mask ventilation or intubation. Additionally, 18 cases
      of mild hypotension were observed in the propofol group, and 11 cases were
      observed in the combination group. The combination group had a lower mean total
      propofol dose (378 mg vs 466 mg, p<0.012), a longer mean recovery time (10.5
      minutes vs 7.9 minutes, p=0.027), and a lower frequency of overall adverse events
      (32.8% vs 17.6%, p=0.042). CONCLUSIONS: Deep sedation induced by continuous
      propofol infusion was shown to be safe during ESD. The combination of continuous
      propofol infusion and intermittent midazolam injection can decrease the total
      dose and infusion rate of propofol and the overall occurrence of adverse events.

PMID- 23170152
TI  - Comparison of internally cooled wet electrode and hepatic vascular inflow
      occlusion method for hepatic radiofrequency ablation.
AB  - BACKGROUND/AIMS: Various strategies to expand the ablation zone have been
      attempted using hepatic radiofrequency ablation (RFA). The optimal strategy,
      however, is unknown. We compared hepatic RFA with an internally cooled wet (ICW)
      electrode and vascular inflow occlusion. METHODS: EIGHT DOGS WERE ASSIGNED TO ONE
      OF THREE GROUPS: only RFA using an internally cooled electrode (group A), RFA
      using an ICW electrode (group B), and RFA using an internally cooled electrode
      with the Pringle maneuver (group C). The ablation zone diameters were measured on
      the gross specimens, and the volume of the ablation zone was calculated. RESULTS:
      The ablation zone volume was greatest in group B (1.82+/-1.23 cm(3)), followed by
      group C (1.22+/-0.47 cm(3)), and then group A (0.48+/-0.33 cm(3)). The volumes
      for group B were significantly larger than the volumes for group A (p=0.030).
      There was no significant difference in the volumes between groups A and C
      (p=0.079) and between groups B and C (p=0.827). CONCLUSIONS: Both the usage of an
      ICW electrode and hepatic vascular occlusion effectively expanded the ablation
      zone. The use of an ICW electrode induced a larger ablation zone with easy
      handling compared with using hepatic vascular occlusion, although this difference
      was not statistically significant.

PMID- 23170153
TI  - Changes in the clinical outcomes of variceal bleeding in cirrhotic patients: a 10
      year experience in gangwon province, South Korea.
AB  - BACKGROUND/AIMS: Variceal rupture is one of the main causes of mortality in
      cirrhotic patients. However, there are limited data on the long-term outcomes of
      variceal bleeding. METHODS: We investigated the incidence and mortality of
      variceal bleeding at three endoscopic centers in Gangwon province during 3
      periods (August 1996 to July 1997, August 2001 to July 2002, and August 2006 to
      July 2007). RESULTS: A total of 1,704 upper gastrointestinal (GI) bleedings
      occurred during the study periods. Peptic ulcers were found in 825 patients
      (48.5%), and variceal ruptures were found in 607 patients (35.6%). The variceal
      bleeding rate did not decrease in each period (26.0% vs 43.7% vs 33.9%,
      respectively). In the variceal bleeding group, the 6-week mortality rate steadily
      and significantly decreased (15.5% vs 10.8% vs 6.4%, respectively, p=0.027). In
      addition, the mortality rate was significantly higher in the variceal bleeding
      group than in the non-variceal bleeding group (10.4% vs 2.0%, p<0.001; odds
      ratio, 5.659; 95% confidence interval, 3.445 to 9.295). CONCLUSIONS: Variceal
      bleeding was still the major cause of upper GI bleedings and did not decrease in
      prevalence over the 10-year period in Gangwon province, South Korea. However, the
      mortality rate of variceal bleeding decreased significantly.

PMID- 23170154
TI  - The risk of cellulitis in cirrhotic patients: a nationwide population-based study
      in taiwan.
AB  - BACKGROUND/AIMS: Cellulitis is a common infectious disease. However, the risk of
      cellulitis in cirrhotic patients is not well established, and whether liver
      cirrhosis is a risk factor for cellulitis remains unknown. This study evaluated
      the relationship between cellulitis and liver cirrhosis. METHODS: The National
      Health Insurance Database, which was derived from the Taiwan National Health
      Insurance program, was used to identify patients. The study group consisted of
      39,966 patients with liver cirrhosis, and the comparison group consisted of
      39,701 randomly selected age- and sex-matched patients. RESULTS: During the 3
      year follow-up period, 2,674 (6.7%) patients with liver cirrhosis developed
      cellulitis, and 1,587 (4.0%) patients without liver cirrhosis developed
      cellulitis (p<0.001). Following a Cox's regression analysis adjusted for age,
      sex, and underlying medical disorders, the cirrhotic patients demonstrated a
      greater risk for the occurrence of cellulitis than the non-cirrhotic patients
      during the 3-year period (hazard ratio [HR], 1.66; 95% confidence interval [CI],
      1.55 to 1.77; p<0.001). Additionally, cirrhotic patients with complications also
      had a greater risk for the occurrence of cellulitis than those patients without
      complications (HR, 1.23; 95% CI, 1.14 to 1.33; p<0.001). CONCLUSIONS: We conclude
      that cirrhotic patients have a greater risk of cellulitis than non-cirrhotic
      patients.

PMID- 23170155
TI  - Long-term treatment efficacy and safety of clevudine therapy in naive patients
      with chronic hepatitis B.
AB  - BACKGROUND/AIMS: Clevudine (CLV) has potent antiviral activity against chronic
      hepatitis B (CHB) virus infection. The long-term efficacy and safety of CLV
      therapy in naive patients with CHB were investigated. METHODS: In this
      retrospective study, 152 naive Korean patients with CHB who received 30 mg of CLV
      once daily for at least 12 months were investigated. RESULTS: The cumulative
      rates at months 12, 24, and 36, respectively, were 65.8%, 74.7%, and 74.7% for
      undetectable serum hepatitis B virus (HBV) DNA (<12 IU/mL); 77.6%, 86.2%, and
      86.2% for normalization of serum alanine aminotransferase (<40 IU/L); 17.6%,
      23.5%, and 23.5% for hepatitis B e antigen (HBeAg) loss or seroconversion; and
      6.6%, 22.5%, and 30.0% for viral breakthrough. HBeAg positivity (p=0.010),
      baseline serum HBV DNA level >=6 log(10) IU/mL (p=0.032) and detectable serum HBV
      DNA (>=12 IU/mL) at week 24 (p=0.023) were independently associated with the
      development of viral breakthrough. During follow-up, CLV-induced myopathy
      developed in 5.9% of patients. CONCLUSIONS: The results of long-term CLV therapy
      for the treatment of naive patients with CHB showed a high frequency of antiviral
      resistance and substantial associated myopathy. Therefore, we advise that CLV
      should not be used as a first-line treatment for naive patients given the
      availability of other more potent, safer antiviral agents.

PMID- 23170156
TI  - Long-term outcome of cystic lesions in the pancreas: a retrospective cohort
      study.
AB  - BACKGROUND/AIMS: The management guidelines for cystic lesions of the pancreas
      (CLPs) are not yet well established. This study was performed to document the
      long-term clinical outcome of CLPs and provide guidelines for the management and
      surveillance of CLPs. METHODS: In this retrospective cohort study, an additional
      follow-up was performed in 112 patients with CLPs enrolled from 1998 to 2004
      during a previous study. RESULTS: During follow-up for the median period of 72.3
      months, the size of the CLPs increased in 18 patients (16.1%). Six of these
      patients experienced growth of their CLPs after 5 years of follow-up. Twenty-six
      patients underwent surgery during follow-up, and four malignant cysts were
      detected. The overall rate of malignant progression during follow-up was 3.6%.
      The presence of mural nodules or solid components was independently associated
      with the presence of malignant CLPs. Seven patients underwent surgery after 5
      years of follow-up. The pathologic findings revealed malignancies in two
      patients. There was only one pancreas-related death during follow-up.
      CONCLUSIONS: The majority of CLPs exhibit indolent behavior and are associated
      with a favorable prognosis. However, long-term surveillance for more than 5 years
      should be performed because of the potential for growth and malignant
      transformation in CLPs.

PMID- 23170157
TI  - Short and long-term outcomes of diabetes mellitus in patients with autoimmune
      pancreatitis after steroid therapy.
AB  - BACKGROUND/AIMS: Autoimmune pancreatitis (AIP) is frequently associated with
      diabetes mellitus (DM). This study evaluated the effect of steroid therapy on the
      course of DM in AIP. METHODS: Glucose tolerance was examined in 69 patients with
      AIP. DM onset was classified as either a simultaneous onset with AIP or an
      exacerbation of pre-existing DM. Based on the changes in the HbA1c levels and
      insulin dose, the responses of DM to steroids were classified as improved, no
      change, or worsened. RESULTS: Thirty (46%) patients were diagnosed as having DM
      (simultaneous onset, n=17; pre-existing, n=13). Three months after starting the
      steroid treatment, the DM improved in 13 (54%) of 24 DM patients. The DM improved
      in 55%, had no change in 36%, and worsened in 9% of the 11 simultaneous onset DM
      patients, and it improved in 54%, had no change in 31%, and worsened in 15% of
      the 13 pre-existing DM patients. At approximately 3 years after starting the
      steroid treatment, the DM improved in 10 (63%) of 16 patients. The pancreatic
      exocrine function improved in parallel with the changes in the DM in seven
      patients. CONCLUSIONS: Because approximately 60% of DM associated with AIP is
      responsive to steroids in the short- and long-terms, marked DM associated with
      AIP appears to be an indication for steroid therapy.

PMID- 23170158
TI  - The effect of intestinal permeability and endotoxemia on the prognosis of acute
      pancreatitis.
AB  - BACKGROUND/AIMS: Early intestinal mucosal damage plays an important role in
      severe acute pancreatitis (AP). Previous studies have shown that intestinal
      permeability (IP), serum endotoxin and cytokines contribute to the early
      intestinal barrier dysfunction in AP. This study explored the predictive capacity
      of IP, endotoxemia and cytokines as prognostic indicators in AP patients.
      METHODS: Eighty-seven AP patients were included in the study. The patients were
      classified into three groups according to the Balthazar computed tomography
      severity index (CTSI). We compared the biochemical parameters, including IP,
      serum endotoxin level and cytokine level among the three groups. The associations
      of IP with serum endotoxin, cytokines, CTSI, and other widely used biochemical
      parameters and scoring systems were also examined. RESULTS: IP, serum endotoxin,
      interleukin (IL-6) and tumor necrosis factor (TNF)-alpha had a positive
      correlation with the CTSI of AP. Endotoxin, IL-6, TNF-alpha, CTSI, the
      Ranson/APACHE II score, the duration of hospital stay, complications and death
      significantly affect IP in the AP patients. CONCLUSIONS: We believe that IP with
      subsidiary measurements of serum endotoxin, IL-6 and TNF-alpha may be reliable
      markers for predicting the prognosis of AP. Further studies that can restore and
      preserve gut barrier function in AP patients are warranted.

PMID- 23170159
TI  - A case of acute myocarditis as the initial presentation of Crohn's disease.
AB  - We experienced a case of acute myocarditis as the initial presentation of Crohn's
      disease. A 19-year-old woman was admitted with impaired consciousness, shock, and
      respiratory failure. She had suffered from frequent diarrhea and abdominal pain
      for several years. Cardiac troponin I and creatine kinase-MB fraction levels were
      elevated to 5.32 and 16.66 ng/mL, respectively. A 12-lead electrocardiogram
      showed sinus tachycardia, and a chest radiograph revealed interstitial pulmonary
      edema. An echocardiogram showed dilated ventricles with akinesia of the basal to
      apical inferoseptal, anteroseptal, anterior, and inferior left ventricular walls
      and severely impaired systolic function. Intensive care with inotropic support
      was effective, and her clinical condition gradually improved. Two weeks later, a
      colonoscopy revealed ulceration with stenosis in the terminal ileum and multiple
      aphthous ulcers in the rectum. A biopsy of the rectum revealed non-caseating
      granulomatous inflammation. She was diagnosed with Crohn's disease presenting
      with acute myocarditis.

PMID- 23170160
TI  - A case of enteropathy-type T-cell lymphoma diagnosed by small bowel enteroscopy:
      a perspective on imaging-enhanced endoscopy.
AB  - Enteropathy-type T-cell lymphoma (ETL) or enteropathy-associated T-cell lymphoma
      is a very rare malignant intestinal tumor. ETL is usually diagnosed by surgery.
      Endoscopic findings of ETL are not well known, and there are few reports of
      findings from endoscopy that has been performed only using white light.
      Additionally, there are no definite treatment guidelines for ETL. Therefore, we
      report a case of ETL diagnosed by enteroscopy with imaging-enhanced endoscopy and
      also review recently developed treatment options.

PMID- 23170161
TI  - A case of nonalcoholic steatohepatitis and small intestinal bacterial overgrowth
      with peripheral edema caused by intestinal bypass surgery and relieved by repair.
AB  - Intestinal bypass surgery, particularly jejuno-ileal bypass surgery, performed
      for the purpose of weight reduction may cause an unexpected exacerbation of
      nonalcoholic steatohepatitis (NASH). Here, we report a case of NASH caused by
      small intestinal bacterial overgrowth, which developed after jejuno-colic bypass
      surgery and resolved dramatically after surgical correction.

PMID- 23170162
TI  - What is the Clinical Relevance of Filiform Polyposis?

PMID- 23170163
TI  - Renal alterations in feline immunodeficiency virus (FIV)-infected cats: a natural
      model of lentivirus-induced renal disease changes.
AB  - Human immunodeficiency virus (HIV) is associated with several renal syndromes
      including acute and chronic renal failures, but the underlying pathogenic
      mechanisms are unclear. HIV and feline immunodeficiency virus (FIV) share
      numerous biological and pathological features, including renal alterations. We
      investigated and compared the morphological changes of renal tissue of 51
      experimentally and 21 naturally infected cats. Compared to the latter, the
      experimentally infected cats exhibited some mesangial widening and
      glomerulonephritis, milder proteinuria, and lower tubular and interstitial
      alterations. The numbers of giant protein tubular casts and tubular microcysts
      were also lower. In contrast, diffuse interstitial infiltrates and glomerular and
      interstitial amyloidosis were detected only in naturally infected cats. Similar
      alterations are found in HIV infected patients, thus supporting the idea of a
      causative role of FIV infection in renal disease, and underlining the relevance
      of the FIV and its natural host as an animal model for investigating lentivirus
      associated nephropathy.

PMID- 23170165
TI  - Structural aspects of the interaction of dairy phages with their host bacteria.
AB  - Knowledge of phage-host interactions at a fundamental level is central to the
      design of rational strategies for the development of phage-resistant strains that
      may be applied in industrial settings. Phages infecting lactic acid bacteria, in
      particular Lactococcus lactis and Streptococcus thermophilus, negatively impact
      on dairy fermentation processes with serious economic implications. In recent
      years a wealth of information on structural protein assembly and topology has
      become available relating to phages infecting Escherichia coli, Bacillus subtilis
      and Lactococcus lactis, which act as models for structural analyses of dairy
      phages. In this review, we explore the role of model tailed phages, such as T4
      and SPP1, in advancing our knowledge regarding interactions between dairy phages
      and their hosts. Furthermore, the potential of currently investigated dairy
      phages to in turn serve as model systems for this particular group of phages is
      discussed.

PMID- 23170164
TI  - MicroRNA-mediated restriction of HIV-1 in resting CD4+ T cells and monocytes.
AB  - In contrast to activated CD4(+) T cells and differentiated macrophages, resting
      CD4(+) T cells and monocytes are non-permissive for HIV-1 replication. The
      mediators which regulate the resting or quiescent phenotype are often actively
      involved in the restriction of viral replication and the establishment and
      maintenance of viral latency. Recently, certain microRNAs which are highly
      expressed in resting cells have been implicated in this capacity, inhibiting the
      expression of cellular proteins that are also viral co-factors; following
      activation these microRNAs exhibit decreased expression, while their targets are
      correspondingly up-regulated, contributing to a favorable milieu for virus
      replication. Other microRNAs exhibiting a similar expression pattern in resting
      and activated cells have been shown to directly target the HIV-1 genome. In this
      review we will discuss the resting state and the causes behind viral restriction
      in resting cells, with emphasis on the role of microRNAs.

PMID- 23170166
TI  - Genetics-based classification of filoviruses calls for expanded sampling of
      genomic sequences.
AB  - We have recently developed a computational approach for hierarchical, genome
      based classification of viruses of a family (DEmARC). In DEmARC, virus clusters
      are delimited objectively by devising a universal family-wide threshold on intra
      cluster genetic divergence of viruses that is specific for each level of the
      classification. Here, we apply DEmARC to a set of 56 filoviruses with complete
      genome sequences and compare the resulting classification to the ICTV taxonomy of
      the family Filoviridae. We find in total six candidate taxon levels two of which
      correspond to the species and genus ranks of the family. At these two levels, the
      six filovirus species and two genera officially recognized by ICTV, as well as a
      seventh tentative species for Lloviu virus and prototyping a third genus, are
      reproduced. DEmARC lends the highest possible support for these two as well as
      the four other levels, implying that the actual number of valid taxon levels
      remains uncertain and the choice of levels for filovirus species and genera is
      arbitrary. Based on our experience with other virus families, we conclude that
      the current sampling of filovirus genomic sequences needs to be considerably
      expanded in order to resolve these uncertainties in the framework of genetics
      based classification.

PMID- 23170169
TI  - Does apoptosis play a role in varicella zoster virus latency and reactivation?
AB  - Varicella zoster virus (VZV) is an exclusively human highly neurotropic
      alphaherpesvirus. To date, VZV has been shown to induce apoptosis, primarily
      through the intrinsic pathway in different cell types, except for neurons in
      which the virus becomes latent. This review summarizes current studies of
      varicella-induced apoptosis in non-neuronal cells. Future studies are proposed to
      determine whether apoptosis is terminated prematurely or even begins in neurons
      that are non-productively infected with VZV.

PMID- 23170168
TI  - Mouse models for filovirus infections.
AB  - The filoviruses marburg- and ebolaviruses can cause severe hemorrhagic fever (HF)
      in humans and nonhuman primates. Because many cases have occurred in geographical
      areas lacking a medical research infrastructure, most studies of the pathogenesis
      of filoviral HF, and all efforts to develop drugs and vaccines, have been carried
      out in biocontainment laboratories in non-endemic countries, using nonhuman
      primates (NHPs), guinea pigs and mice as animal models. NHPs appear to closely
      mirror filoviral HF in humans (based on limited clinical data), but only small
      numbers may be used in carefully regulated experiments; much research is
      therefore done in rodents. Because of their availability in large numbers and the
      existence of a wealth of reagents for biochemical and immunological testing, mice
      have become the preferred small animal model for filovirus research. Since the
      first experiments following the initial 1967 marburgvirus outbreak, wild-type or
      mouse-adapted viruses have been tested in immunocompetent or immunodeficient
      mice. In this paper, we review how these types of studies have been used to
      investigate the pathogenesis of filoviral disease, identify immune responses to
      infection and evaluate antiviral drugs and vaccines. We also discuss the
      strengths and weaknesses of murine models for filovirus research, and identify
      important questions for further study.

PMID- 23170170
TI  - Emaravirus: a novel genus of multipartite, negative strand RNA plant viruses.
AB  - Ringspot symptoms in European mountain ash (Sorbus aucuparia L.), fig mosaic,
      rose rosette, raspberry leaf blotch, pigeonpea sterility mosaic (Cajanus cajan)
      and High Plains disease of maize and wheat were found to be associated with
      viruses that share several characteristics. They all have single-stranded
      multipartite RNA genomes of negative orientation. In some cases, double membrane
      bound virus-like particles of 80 to 200 nm in diameter were found in infected
      tissue. Furthermore, at least five of these viruses were shown to be vectored by
      eriophyid mites. Sequences of European mountain ash ringspot-associated virus
      (EMARaV), Fig mosaic virus (FMV), rose rosette virus (RRV), raspberry leaf blotch
      virus (RLBV), pigeonpea sterility mosaic virus and High Plains virus strongly
      support their potential phylogenetic relationship. Therefore, after
      characterization of EMARaV, the novel genus Emaravirus was established, and FMV
      was the second virus species assigned to this genus. The recently sequenced RRV
      and RLBV are supposed to be additional members of this new group of plant RNA
      viruses.

PMID- 23170171
TI  - Contributions of Epstein-Barr nuclear antigen 1 (EBNA1) to cell immortalization
      and survival.
AB  - Epstein-Barr virus (EBV) immortalizes host cells as part of its latent mode of
      infection. As a result of this ability to promote cell proliferation and
      survival, EBV infection contributes to the development of several kinds of B-cell
      lymphomas and epithelial tumours. The EBV Epstein-Barr nuclear antigen 1 (EBNA1)
      protein is the only EBV protein expressed in all EBV-associated tumours and plays
      multiple important roles in EBV latency. In addition to its well-studied roles in
      viral DNA replication, segregation and transcriptional activation, several
      studies have identified roles of EBNA1 in manipulating cellular processes that
      result in reduced apoptosis and increased cell survival. This review discusses
      these cellular effects of EBNA1 and mechanisms by which they occur.

PMID- 23170172
TI  - Genomic sequences of two novel levivirus single-stranded RNA coliphages (family
      Leviviridae): evidence for recombinationin environmental strains.
AB  - Bacteriophages are likely the most abundant entities in the aquatic environment,
      yet knowledge of their ecology is limited. During a fecal source-tracking study,
      two genetically novel Leviviridae strains were discovered. Although the novel
      strains were isolated from coastal waters 1130 km apart (North Carolina and Rhode
      Island, USA), these strains shared 97% nucleotide similarity and 97-100% amino
      acid similarity. When the novel strains were compared to nine Levivirus genogroup
      I strains, they shared 95-100% similarity among the maturation, capsid and lysis
      proteins, but only 84-85% in the RNA-dependent RNA polymerase gene. Further
      bioinformatic analyses suggested a recombination event occurred. To the best of
      our knowledge, this is the first description of viral recombinants in
      environmental Leviviridae ssRNA bacteriophages.

PMID- 23170167
TI  - Evasion of influenza A viruses from innate and adaptive immune responses.
AB  - The influenza A virus is one of the leading causes of respiratory tract
      infections in humans. Upon infection with an influenza A virus, both innate and
      adaptive immune responses are induced. Here we discuss various strategies used by
      influenza A viruses to evade innate immune responses and recognition by
      components of the humoral and cellular immune response, which consequently may
      result in reduced clearing of the virus and virus-infected cells. Finally, we
      discuss how the current knowledge about immune evasion can be used to improve
      influenza A vaccination strategies.

PMID- 23170174
TI  - Filovirus research in Gabon and equatorial Africa: the experience of a research
      center in the heart of Africa.
AB  - Health research programs targeting the population of Gabon and Equatorial Africa
      at the International Center for Medical Research in Franceville (CIRMF), Gabon,
      have evolved during the years since its inception in 1979 in accordance with
      emerging diseases. Since the reemergence of Ebola virus in Central Africa, the
      CIRMF "Emerging Viral Disease Unit" developed diagnostic tools and epidemiologic
      strategies and transfers of such technology to support the response of the
      National Public Health System and the World Health Organization to epidemics of
      Ebola virus disease. The Unit carries out a unique investigation program on the
      natural history of the filoviruses, emergence of epidemics, and Ebola virus
      pathogenesis. In addition, academic training is provided at all levels to
      regional and international students covering emerging conditions (host factors,
      molecular biology, genetics) that favor the spread of viral diseases.

PMID- 23170173
TI  - Host cell factors as antiviral targets in arenavirus infection.
AB  - Among the members of the Arenaviridae family, Lassa virus and Junin virus
      generate periodic annual outbreaks of severe human hemorrhagic fever (HF) in
      endemic areas of West Africa and Argentina, respectively. Given the human health
      threat that arenaviruses represent and the lack of a specific and safe
      chemotherapy, the search for effective antiviral compounds is a continuous
      demanding effort. Since diverse host cell pathways and enzymes are used by RNA
      viruses to fulfill their replicative cycle, the targeting of a host process has
      turned an attractive antiviral approach in the last years for many unrelated
      virus types. This strategy has the additional benefit to reduce the serious
      challenge for therapy of RNA viruses to escape from drug effects through
      selection of resistant variants triggered by their high mutation rate. This
      article focuses on novel strategies to identify inhibitors for arenavirus
      therapy, analyzing the potential for antiviral developments of diverse host
      factors essential for virus infection.

PMID- 23170175
TI  - Cytopathogenesis of vesicular stomatitis virus is regulated by the PSAP motif of
      M protein in a species-dependent manner.
AB  - Vesicular stomatitis virus (VSV) is an important vector-borne pathogen of bovine
      and equine species, causing a reportable vesicular disease. The matrix (M)
      protein of VSV is multifunctional and plays a key role in cytopathogenesis,
      apoptosis, host protein shut-off, and virion assembly/budding. Our previous
      findings indicated that mutations of residues flanking the (37)PSAP(40) motif
      within the M protein resulted in VSV recombinants having attenuated phenotypes in
      mice. In this report, we characterize the phenotype of VSV recombinant PS > A4
      (which harbors four alanines (AAAA) in place of the PSAP motif without disruption
      of flanking residues) in both mice, and in Aedes albopictus C6/36 mosquito and
      Culicoides sonorensis KC cell lines. The PS > A4 recombinant displayed an
      attenuated phenotype in infected mice as judged by weight loss, mortality, and
      viral titers measured from lung and brain samples of infected animals. However,
      unexpectedly, the PS > A4 recombinant displayed a robust cytopathic phenotype in
      insect C6/36 cells compared to that observed with control viruses. Notably,
      titers of recombinant PS > A4 were approximately 10-fold greater than those of
      control viruses in infected C6/36 cells and in KC cells from Culicoides
      sonorensis, a known VSV vector species. In addition, recombinant PS > A4 induced
      a 25-fold increase in the level of C3 caspase activity in infected C6/36 cells.
      These findings indicate that the PSAP motif plays a direct role in regulating
      cytopathogenicity in a species-dependent manner, and suggest that the intact PSAP
      motif may be important for maintaining persistence of VSV in an insect host.

PMID- 23170177
TI  - Uncovering viral protein-protein interactions and their role in arenavirus life
      cycle.
AB  - The Arenaviridae family includes widely distributed pathogens that cause severe
      hemorrhagic fever in humans. Replication and packaging of their single-stranded
      RNA genome involve RNA recognition by viral proteins and a number of key protein
      protein interactions. Viral RNA synthesis is directed by the virus-encoded RNA
      dependent-RNA polymerase (L protein) and requires viral RNA encapsidation by the
      Nucleoprotein. In addition to the role that the interaction between L and the
      Nucleoprotein may have in the replication process, polymerase activity appears to
      be modulated by the association between L and the small multifunctional Z
      protein. Z is also a structural component of the virions that plays an essential
      role in viral morphogenesis. Indeed, interaction of the Z protein with the
      Nucleoprotein is critical for genome packaging. Furthermore, current evidence
      suggests that binding between Z and the viral envelope glycoprotein complex is
      required for virion infectivity, and that Z homo-oligomerization is an essential
      step for particle assembly and budding. Efforts to understand the molecular basis
      of arenavirus life cycle have revealed important details on these viral protein
      protein interactions that will be reviewed in this article.

PMID- 23170176
TI  - Potential vaccines and post-exposure treatments for filovirus infections.
AB  - Viruses of the family Filoviridae represent significant health risks as emerging
      infectious diseases as well as potentially engineered biothreats. While many
      research efforts have been published offering possibilities toward the mitigation
      of filoviral infection, there remain no sanctioned therapeutic or vaccine
      strategies. Current progress in the development of filovirus therapeutics and
      vaccines is outlined herein with respect to their current level of testing,
      evaluation, and proximity toward human implementation, specifically with regard
      to human clinical trials, nonhuman primate studies, small animal studies, and in
      vitro development. Contemporary methods of supportive care and previous treatment
      approaches for human patients are also discussed.

PMID- 23170178
TI  - Clinical management of filovirus-infected patients.
AB  - Filovirus infection presents many unique challenges to patient management.
      Currently no approved treatments are available, and the recommendations for
      supportive care are not evidence based. The austere clinical settings in which
      patients often present and the sporadic and at times explosive nature of
      filovirus outbreaks have effectively limited the information available to
      evaluate potential management strategies. This review will summarize the
      management approaches used in filovirus outbreaks and provide recommendations for
      collecting the information necessary for evaluating and potentially improving
      patient outcomes in the future.

PMID- 23170179
TI  - Emerging themes from EBV and KSHV microRNA targets.
AB  - EBV and KSHV are both gamma-herpesviruses which express multiple viral microRNAs.
      Various methods have been used to investigate the functions of these microRNAs,
      largely through identification of microRNA target genes. Surprisingly, these
      related viruses do not share significant sequence homology in their microRNAs. A
      number of reports have described functions of EBV and KSHV microRNA targets,
      however only three experimentally validated target genes have been shown to be
      targeted by microRNAs from both viruses. More sensitive methods to identify
      microRNA targets have predicted approximately 60% of host targets could be shared
      by EBV and KSHV microRNAs, but by targeting different sequences in the host
      targets. In this review, we explore the similarities of microRNA functions and
      targets of these related viruses.

PMID- 23170180
TI  - Human leukocyte antigen (HLA) class I down-regulation by human immunodeficiency
      virus type 1 negative factor (HIV-1 Nef): what might we learn from natural
      sequence variants?
AB  - HIV-1 causes a chronic infection in humans that is characterized by high plasma
      viremia, progressive loss of CD4+ T lymphocytes, and severe immunodeficiency
      resulting in opportunistic disease and AIDS. Viral persistence is mediated in
      part by the ability of the Nef protein to down-regulate HLA molecules on the
      infected cell surface, thereby allowing HIV-1 to evade recognition by antiviral
      CD8+ T lymphocytes. Extensive research has been conducted on Nef to determine
      protein domains that are required for its immune evasion activities and to
      identify critical cellular co-factors, and our mechanistic understanding of this
      process is becoming more complete. This review highlights our current knowledge
      of Nef-mediated HLA class I down-regulation and places this work in the context
      of naturally occurring sequence variation in this protein. We argue that efforts
      to fully understand the critical role of Nef for HIV-1 pathogenesis will require
      greater analysis of patient-derived sequences to elucidate subtle differences in
      immune evasion activity that may alter clinical outcome.

PMID- 23170183
TI  - PepGMV rep-protein expression in mammalian cells.
AB  - The Geminiviruses genome is a small, single strand DNA that replicates in the
      plant cell nucleus. Analogous to animal DNA viruses, Geminiviruses depend on the
      host replication machinery to amplify their genomes and only supply the factors
      required to initiate their replication. Consequently, Geminiviruses remove the
      cell-cycle arrest and induce the host replication machinery using an endocycle
      process. They encode proteins, such as the conserved replication-associated
      proteins (Rep) that interact with retinoblastoma-like proteins in plants and
      alter the cell division cycle in yeasts. Therefore, the aim of this work is to
      analyze the impact of Pepper Golden Mosaic Virus (PepGMV) Rep protein in
      mammalian cells. Results indicate that the pTracer-SV40:Rep construction obtained
      in this work can be used to analyze the Rep protein effect in mammalian cells in
      order to compare the cell cycle regulation mechanisms in plants and animals.

PMID- 23170182
TI  - Diversity of dicotyledenous-infecting geminiviruses and their associated DNA
      molecules in southern Africa, including the South-west Indian ocean islands.
AB  - The family Geminiviridae comprises a group of plant-infecting circular ssDNA
      viruses that severely constrain agricultural production throughout the temperate
      regions of the world, and are a particularly serious threat to food security in
      sub-Saharan Africa. While geminiviruses exhibit considerable diversity in terms
      of their nucleotide sequences, genome structures, host ranges and insect vectors,
      the best characterised and economically most important of these viruses are those
      in the genus Begomovirus. Whereas begomoviruses are generally considered to be
      either monopartite (one ssDNA component) or bipartite (two circular ssDNA
      components called DNA-A and DNA-B), many apparently monopartite begomoviruses are
      associated with additional subviral ssDNA satellite components, called alpha-
      (DNA-alphas) or betasatellites (DNA-betas). Additionally, subgenomic molecules,
      also known as defective interfering (DIs) DNAs that are usually derived from the
      parent helper virus through deletions of parts of its genome, are also associated
      with bipartite and monopartite begomoviruses. The past three decades have
      witnessed the emergence and diversification of various new begomoviral species
      and associated DI DNAs, in southern Africa, East Africa, and proximal Indian
      Ocean islands, which today threaten important vegetable and commercial crops such
      as, tobacco, cassava, tomato, sweet potato, and beans. This review aims to
      describe what is known about these viruses and their impacts on sustainable
      production in this sensitive region of the world.

PMID- 23170181
TI  - Neutralization interfering antibodies: a "novel" example of humoral immune
      dysfunction facilitating viral escape?
AB  - The immune response against some viral pathogens, in particular those causing
      chronic infections, is often ineffective notwithstanding a robust humoral
      neutralizing response. Several evasion mechanisms capable of subverting the
      activity of neutralizing antibodies (nAbs) have been described. Among them, the
      elicitation of non-neutralizing and interfering Abs has been hypothesized.
      Recently, this evasion mechanism has acquired an increasing interest given its
      possible impact on novel nAb-based antiviral therapeutic and prophylactic
      approaches. In this review, we illustrate the mechanisms of Ab-mediated
      interference and the viral pathogens described in literature as able to adopt
      this "novel" evasion strategy.

PMID- 23170184
TI  - Animal models, prophylaxis, and therapeutics for arenavirus infections.
AB  - Arenaviruses are enveloped, bipartite negative single-stranded RNA viruses that
      can cause a wide spectrum of disease in humans and experimental animals including
      hemorrhagic fever. The majority of these viruses are rodent-borne and the
      arenavirus family can be divided into two groups: the Lassa-Lymphocytic
      choriomeningitis serocomplex and the Tacaribe serocomplex. Arenavirus-induced
      disease may include characteristic symptoms ranging from fever, malaise, body
      aches, petechiae, dehydration, hemorrhage, organ failure, shock, and in severe
      cases death. Currently, there are few prophylactic and therapeutic treatments
      available for arenavirus-induced symptoms. Supportive care and ribavirin remain
      the predominant strategies for treating most of the arenavirus-induced diseases.
      Therefore, efficacy testing of novel therapeutic and prophylactic strategies in
      relevant animal models is necessary. Because of the potential for person-to
      person spread, the ability to cause lethal or debilitating disease in humans,
      limited treatment options, and potential as a bio-weapon, the development of
      prophylactics and therapeutics is essential. This article reviews the current
      arenavirus animal models and prophylactic and therapeutic strategies under
      development to treat arenavirus infection.

PMID- 23170186
TI  - Clinical profile of patients with rare inherited coagulation disorders: a
      retrospective analysis of 67 patients from northern India.
AB  - INTRODUCTION: Inherited bleeding disorders are characterized by the absence or
      reduced level of clotting factors, and the clinical manifestations vary according
      to the type and magnitude of the deficient factor. AIM: To study the clinical
      presentation of the rare inherited coagulation factor disorders in a tertiary
      care hospital and to compare the data from those reported in other populations.
      METHODS: Sixty-seven patients, who presented to the Department of Hematology, All
      India Institute of Medical Sciences, New Delhi, were evaluated retrospectively
      from 2005 to 2011. The tests performed included platelet count, prothrombin time
      (PT), activated partial thromboplastin time (aPTT), thrombin time (TT), factors
      assay and clot solubility test in 5 M urea. Factor XI assays were aPTT based
      while factors V, VII and X assays were PT based. RESULTS: Male to female ratio
      was 2:1. The median age of onset of the first episode of bleeding was at 6 months
      (range, from birth to 20 years) whereas the median age of presentation to our
      hospital was 9 years (range, 2 months to 54 years). The most common deficient
      factor was factor X (43%), followed by factor XIII (27%) and factor VII (10%).
      CONCLUSION: There is a wide gap between the initial manifestation of the bleeding
      disorders and first presentation to the tertiary care hospital for assessment and
      treatment. Factor X deficiency is the most common among these rare coagulation
      disorders in our population, whereas factor VII deficiency is more common in
      Iranian and North American population.

PMID- 23170185
TI  - Construction of a high titer infectious HIV-1 subtype C proviral clone from South
      Africa.
AB  - The Human Immunodeficiency Virus type 1 (HIV-1) subtype C is currently the
      predominant subtype worldwide. Cell culture studies of Sub-Saharan African
      subtype C proviral plasmids are hampered by the low replication capacity of the
      resulting viruses, although viral loads in subtype C infected patients are as
      high as those from patients with subtype B. Here, we describe the sequencing and
      construction of a new HIV-1 subtype C proviral clone (pZAC), replicating more
      than one order of magnitude better than the previous subtype C plasmids. We
      identify the env-region for being the determinant for the higher viral titers and
      the pZAC Env to be M-tropic. This higher replication capacity does not lead to a
      higher cytotoxicity compared to previously described subtype C viruses. In
      addition, the pZAC Vpu is also shown to be able to down-regulate CD4, but fails
      to fully counteract CD317.

PMID- 23170187
TI  - Quality of life in patients with thalassemia major and intermedia in kerman-iran
      (I.R.).
AB  - Thalassemia is the most common hemoglobin disorder in the world and thalassemia
      major and intermedia stand among the most severe forms. Due to recent
      improvements in treatment, patients with thalassemia have longer life
      expectancies; hence it is of utmost importance to pay careful attention to their
      quality of life together with life expectancy. This study was conducted to assess
      the quality of life in patients with thalassemia and also to compare it between
      thalassemia major and intermedia. In this cross-sectional study, patients who
      referred for blood transfusion or follow-up visits were evaluated for their
      quality of life (QOL). Short Form-36 questionnaire was applied to evaluate QOL.
      In this study, 308 patients with a mean age of 22.95+/-4.82 years were evaluated.
      The scores of QOL were regarded as moderate in eight domains under evaluation;
      the least score was given to General Health (53.05+/-16.96) whereas the highest
      score was given to Physical Functioning (67.95+/-22.68). The QOL in the patients
      with thalassemia major was better than those with thalassemia intermedia
      regarding Physical Functioning and Role Limitation Emotional domains. Compared to
      injecting chelators, patients who received oral chelators showed to have a better
      QOL considering Social Functioning and Mental Health domain. The patients under
      study didn't have a satisfying QOL ; the QOL of patients with thalassemia major
      was better than that of patients with thalassemia intermedia in only 2 domains of
      sf-36(Physical Functioning & Role limitation-Emotional). It is then essential
      that experts pay proper attention to improve QOL among patients.

PMID- 23170188
TI  - Role of hematopoietic stem cell transplantation in relapsed/refractory hodgkin
      lymphoma.
AB  - Hodgkin lymphoma is one of the most curable human tumors. Despite this, about 30%
      of these patients relapsed or are primary refractory to the first line treatment.
      Autografting is generally considered the standard of care for these patients.
      Alternative salvage strategies have been evaluated such as high dose sequential
      and tandem autografting strategies. In younger patients, refractory or early
      relapsed after autografting, allogeneic stem cell transplantation has been
      employed but this approach has been followed by significant concerns since the
      treatment related mortality, often exceeded 40-50%, and relapses were not
      uncommon. It is clear that patient selection remains an issue in all allografting
      reports.At the end, new drugs and novel treatment strategies, that are based on
      our understanding of the disease biology and signaling pathways, are needed to
      improve treatment outcome for these patients. The two leading compounds
      Brentuximab Vedotin and Panobinostat, are currently under evaluation in several
      clinical trials.

PMID- 23170189
TI  - Epidemiology of malaria in endemic areas.
AB  - Malaria infection is still to be considered a major public health problem in
      those 106 countries where the risk of contracting the infection with one or more
      of the Plasmodium species exists. According to estimates from the World Health
      Organization, over 200 million cases and about 655.000 deaths have occurred in
      2010. Estimating the real health and social burden of the disease is a difficult
      task, because many of the malaria endemic countries have limited diagnostic
      resources, especially in rural settings where conditions with similar clinical
      picture may coexist in the same geographical areas. Moreover, asymptomatic
      parasitaemia may occur in high transmission areas after childhood, when anti
      malaria semi-immunity occurs. Malaria endemicity and control activities are very
      complex issues, that are influenced by factors related to the host, to the
      parasite, to the vector, to the environment and to the health system capacity to
      fully implement available anti-malaria weapons such as rapid diagnostic tests,
      artemisinin-based combination treatment, impregnated bed-nets and insecticide
      residual spraying while waiting for an effective vaccine to be made available.

PMID- 23170191
TI  - Chemotherapy-Induced Neutropenia in HIV Positive Patients with Lymphoma:
      Comparison of Pegfilgrastim with Daily Filgrastim Administration.
AB  - We retrospectively compared the incidence of neutropenia in two groups of HIV
      patients with lymphoma, who underwent chemotherapy supported by once-per-cycle
      administration of pegfilgrastim or by daily subcutaneous injection of filgrastim,
      respectively. Our findings indicate that pegfilgrastim and filgastrim produce
      similar results in preventing both neutropenia and febrile neutropenia.

PMID- 23170190
TI  - Pathogenesis of malaria in tissues and blood.
AB  - The clinical manifestations of severe malaria are several and occur in different
      anatomical sites. Both parasite- and host-related factors contribute to the
      pathogenicity of the severe forms of the disease. Cytoadherence of infected red
      blood cells to the vascular endothelium of different organs and rosetting are
      unique features of malaria parasites which are likely to contribute to the
      vascular damage and the consequent excessive inflammatory/immune response of the
      host. In addition to cerebral malaria or severe anaemia, which are quite common
      manifestation of severe malaria, clinical evidences of thrombocytopenia, acute
      respiratory distress syndrome (ARDS), liver and kidney disease, are reported. In
      primigravidae from endemic areas, life threatening placental malaria may also be
      present.In the following pages, some of the pathogenetic aspects will be briefly
      reviewed and then data on selected and less frequent manifestation of severe
      malaria, such as liver or renal failure or ARDS will be discussed.

PMID- 23170192
TI  - Flow cytometry method as a diagnostic tool for pleural fluid involvement in a
      patient with multiple myeloma.
AB  - Multiple myeloma is a malignant proliferation of plasma cells that mainly affects
      bone marrow. Pleural effusions secondary to pleural myelomatous involvement have
      rarely been reported in the literature. As it is rarely detected, we aimed to
      report a case in which pleural effusion of a multiple myeloma was confirmed as
      true myelomatous involvement by flow cytometry method. A 52-years old man
      presented to our clinic with chest and back pain lasting for 3 months. On the
      chest radiography, pleural fluid was detected in left hemithorax. Pleural fluid
      flow cytometry was performed. In the flow cytometry, CD56, CD38 and CD138 found
      to be positive, while CD19 was negative. True myelomatous pleural effusions are
      very uncommon, with fewer than 100 cases reported worldwide. Flow cytometry is a
      potentially useful and simple method for detection of pleural fluid involvement
      in multiple myeloma.

PMID- 23170193
TI  - Advances in the treatment of malaria.
AB  - Malaria still claims a heavy toll of deaths and disabilities even at the
      beginning of the third millennium. The inappropriate sequential use of drug
      monotherapy in the past has facilitated the spread of drug-resistant P.
      falciparum, and to a lesser extend P. vivax, strains in most of the malaria
      endemic areas, rendering most anti-malarial ineffective. In the last decade, a
      new combination strategy based on artemisinin derivatives (ACT) has become the
      standard of treatment for most P. falciparum malaria infections. This strategy
      could prevent the selection of resistant strains by rapidly decreasing the
      parasitic burden (by the artemisinin derivative, mostly artesunate) and exposing
      the residual parasite to effective concentrations of the partner drug. The
      widespread use of this strategy is somehow constrained by cost and by the
      inappropriate use of artemisinin, with possible impact on resistance, as already
      sporadically observed in South East Asia. Parenteral artesunate has now become
      the standard of care for severe malaria, even if quinine still retains its value
      in case artesunate is not immediately available. The appropriateness of pre
      referral use of suppository artesunate is under close monitoring, while waiting
      for an effective anti-malarial vaccine to be made available.

PMID- 23170194
TI  - Sickle cell anaemia and malaria.
AB  - Sickle cell anaemia is a major chapter within haemolytic anaemias; at the same
      time, its epidemiology is a remarkable signature of the past and present world
      distribution of Plasmodium falciparum malaria. In this brief review, in keeping
      with the theme of this journal, we focus on the close and complex relationship
      betweeen this blood disease and this infectious disease. On one hand,
      heterozygotes for the sickle gene (AS) are relatively protected against the
      danger of dying of malaria, as now firmly established through a number of
      clinical field studies from different parts of Africa. In addition, experimental
      work is consistent with a plausibile mechanism: namely, that in AS heterozygotes
      P falciparum-infected red cells sickle preferentially and are then removed by
      macrophages. On the other hand, patients who are homozygous for the sickle gene
      and therefore suffer from sickle cell anaemia (SCA) are highly susceptible to the
      lethal effects of malaria. The simplest explanation of this fact is that malaria
      makes the anaemia of SCA more severe; in addition, in SCA there is often
      hyposplenism, which reduces clearance of parasites. From the point of view of
      public health it is important that in malaria-endemic countries patients with
      SCA, and particularly children, be protected from malaria by appropriate
      prophylaxis.

PMID- 23170195
TI  - New strategies for stem cell mobilization.
AB  - Mobilized peripheral blood (PB) is widely used as source of stem cells (PBSCs)
      for autologous stem cell transplantation (ASCT). The use of cytokines, alone or
      in combination with chemotherapy (chemomobilization), is the most common strategy
      applied to mobilize and collect PBSCs. However, a significant proportion of
      cancer patients fail to mobilize enough PBSCs to proceed to ASCT. Plerixafor is a
      small molecule that reversibly and transiently disrupts the interaction between
      the chemokine receptor CXCR4 and its ligand CXCL12 (formerly known as stroma
      derived factor 1, SDF-1) leading to the rapid release of CD34(+) hematopoietic
      stem cells from the bone marrow (BM) to PB. Plerixafor has been recently approved
      to enhance PBSC mobilization in adult patients with multiple myeloma or non
      Hodgkin lymphoma and has been shown to be more effective than G-CSF alone. There
      is limited experience on combining plerixafor with chemotherapy plus G-CSF in
      patients who mobilize poorly. Current evidence suggests that the addition of
      plerixafor is safe and effective in the large majority of the patients with low
      blood CD34(+) cell count after mobilization and/or poor yield after the first
      collection(s). Circulating CD34(+) cells can be increased by several folds with
      plerixafor and the majority of the patients considered "poor mobilizers" can be
      successfully collected. Overall, its mechanism of action inducing the rapid
      release of CD34(+) cells from the BM to the circulation makes plerixafor suitable
      for the 'preemptive' use in patients who are hard-to-mobilize.

PMID- 23170197
TI  - Broadband and broadangle SPP antennas based on plasmonic crystals with linear
      chirp.
AB  - Plasmonic technology relies on the coupling of light to surface electromagnetic
      modes on smooth or structured metal surfaces. While some applications utilise the
      resonant nature of surface polaritons, others require broadband characteristics.
      We demonstrate unidirectional and broadband plasmonic antennas with large
      acceptance angles based on chirped plasmonic gratings. Near-field optical
      measurements have been used to visualise the excitation of surface plasmon
      polaritons by such aperiodic structures. These weakly aperiodic plasmonic
      crystals allow the formation of a trapped rainbow-type effect in a two
      dimensional geometry as surface polaritons of different frequencies are
      coherently excited in different locations over the plasmonic structure. Both the
      crystal's finite size and the finite lifetime of plasmonic states are crucial for
      the generation of broadband surface plasmon polaritons. This approach presents
      new opportunities for building unidirectional, broadband and broad-angle
      plasmonic couplers for sensing purposes, information processing, photovoltaic
      applications and shaping and manipulating ultrashort optical pulses.

PMID- 23170196
TI  - Novel Agents and Emerging Strategies for Targeting the B-Cell Receptor Pathway in
      CLL.
AB  - Chronic lymphocytic leukemia (CLL) is a disease of malignant CD5+ B lymphocytes
      that are characterized by frequent expression of autoreactive B-cell receptors
      (BCRs) and marked dependence on microenvironmental signals for proliferation and
      survival. Among the latter, signals propagated through the BCR are believed to
      play a key role in leukemia initiation, maintenance and evolution. Drugs that can
      disrupt these signals have recently emerged as potential therapeutic agents in
      CLL and several of them are currently being evaluated in clinical trials.
      Particularly promising clinical responses have been obtained with inhibitors of
      the kinases SYK, BTK, and PI3Kdelta, which function by blocking BCR signal
      transduction. In addition, recent studies focusing on the phosphatase PTPN22,
      which is involved in the pathogenesis of multiple autoimmune diseases and is
      markedly overexpressed in CLL cells, suggest that it may be possible in the
      future to develop strategies that will selectively reprogram BCR survival signals
      into signals that induce leukemic cell death. This review focuses on the
      biological basis behind these strategies and highlights some of the most
      promising BCR-targeting agents in ongoing preclinical and clinical studies.

PMID- 23170198
TI  - Oscillons, solitons, and domain walls in arrays of nonlinear plasmonic
      nanoparticles.
AB  - The study of metal nanoparticles plays a central role in the emerging novel
      technologies employing optics beyond the diffraction limit. Combining strong
      surface plasmon resonances, high intrinsic nonlinearities and deeply
      subwavelength scales, arrays of metal nanoparticles offer a unique playground to
      develop novel concepts for light manipulation at the nanoscale. Here we suggest a
      novel principle to control localized optical energy in chains of nonlinear
      subwavelength metal nanoparticles based on the fundamental nonlinear phenomenon
      of modulation instability. In particular, we demonstrate that modulation
      instability can lead to the formation of long-lived standing and moving nonlinear
      localized modes of several distinct types such as bright and dark solitons,
      oscillons, and domain walls. We analyze the properties of these nonlinear
      localized modes and reveal different scenarios of their dynamics including
      transformation of one type of mode to another. We believe this work paves a way
      towards the development of nonlinear nanophotonics circuitry.

PMID- 23170200
TI  - Fibrin clots are equilibrium polymers that can be remodeled without proteolytic
      digestion.
AB  - Fibrin polymerization is a necessary part of hemostasis but clots can obstruct
      blood vessels and cause heart attacks and strokes. The polymerization reactions
      are specific and controlled, involving strong knob-into-hole interactions to
      convert soluble fibrinogen into insoluble fibrin. It has long been assumed that
      clots and thrombi are stable structures until proteolytic digestion. On the
      contrary, using the technique of fluorescence recovery after photobleaching, we
      demonstrate here that there is turnover of fibrin in an uncrosslinked clot. A
      peptide representing the knobs involved in fibrin polymerization can compete for
      the holes and dissolve a preformed fibrin clot, or increase the fraction of
      soluble oligomers, with striking rearrangements in clot structure. These results
      imply that in vivo clots or thrombi are more dynamic structures than previously
      believed that may be remodeled as a result of local environmental conditions, may
      account for some embolization, and suggest a target for therapeutic intervention.

PMID- 23170199
TI  - Regulation of autophagy by nucleoporin Tpr.
AB  - The nuclear pore complex (NPC) consists of a conserved set of ~30 different
      proteins, termed nucleoporins, and serves as a gateway for the exchange of
      materials between the cytoplasm and nucleus. Tpr (translocated promoter region)
      is a component of NPC that presumably localizes at intranuclear filaments. Here,
      we show that Tpr knockdown caused a severe reduction in the number of nuclear
      pores. Furthermore, our electron microscopy studies indicated a significant
      reduction in the number of inner nuclear filaments. In addition, Tpr siRNA
      treatment impaired cell growth and proliferation compared to control siRNA
      treated cells. In Tpr-depleted cells, the levels of p53 and p21 proteins were
      enhanced. Surprisingly, Tpr depletion increased p53 nuclear accumulation and
      facilitated autophagy. Our study demonstrates for the first time that Tpr plays a
      role in autophagy through controlling HSP70 and HSF1 mRNA export, p53 trafficking
      with karyopherin CRM1, and potentially through direct transcriptional regulation
      of autophagy factors.

PMID- 23170201
TI  - What does population structure analysis reveal about the Pterostylis longifolia
      complex (Orchidaceae)?
AB  - Morphologically similar groups of species are common and pose significant
      challenges for taxonomists. Differences in approaches to classifying unique
      species can result in some species being overlooked, whereas others are wrongly
      conserved. The genetic diversity and population structure of the Pterostylis
      longifolia complex (Orchidaceae) in Tasmania was investigated to determine if
      four species, and potential hybrids, could be distinguished through genomic AFLP
      and chloroplast restriction-fragment-length polymorphism (RFLP) markers. Analysis
      of molecular variance (AMOVA) results indicated that little genetic variation was
      present among taxa, whereas PCoA analyses revealed genetic variation at a
      regional scale irrespective of taxa. Population genetic structure analyses
      identified three clusters that correspond to regional genetic and single taxon
      specific phenotypic variation. The results from this study suggest that
      "longifolia" species have persisted throughout the last glacial maximum in
      Tasmania and that the complex may be best treated as a single taxon with several
      morphotypes. These results could have serious evolutionary and conservation
      implications as taxonomic changes could result in the instatement of a single,
      widespread taxon in which rarer morphotypes are not protected.

PMID- 23170202
TI  - Extreme climatic events drive mammal irruptions: regression analysis of 100-year
      trends in desert rainfall and temperature.
AB  - Extreme climatic events, such as flooding rains, extended decadal droughts and
      heat waves have been identified increasingly as important regulators of natural
      populations. Climate models predict that global warming will drive changes in
      rainfall and increase the frequency and severity of extreme events. Consequently,
      to anticipate how organisms will respond we need to document how changes in
      extremes of temperature and rainfall compare to trends in the mean values of
      these variables and over what spatial scales the patterns are consistent. Using
      the longest historical weather records available for central Australia - 100
      years - and quantile regression methods, we investigate if extreme climate events
      have changed at similar rates to median events, if annual rainfall has increased
      in variability, and if the frequency of large rainfall events has increased over
      this period. Specifically, we compared local (individual weather stations) and
      regional (Simpson Desert) spatial scales, and quantified trends in median (50th
      quantile) and extreme weather values (5th, 10th, 90th, and 95th quantiles). We
      found that median and extreme annual minimum and maximum temperatures have
      increased at both spatial scales over the past century. Rainfall changes have
      been inconsistent across the Simpson Desert; individual weather stations showed
      increases in annual rainfall, increased frequency of large rainfall events or
      more prolonged droughts, depending on the location. In contrast to our
      prediction, we found no evidence that intra-annual rainfall had become more
      variable over time. Using long-term live-trapping records (22 years) of desert
      small mammals as a case study, we demonstrate that irruptive events are driven by
      extreme rainfalls (>95th quantile) and that increases in the magnitude and
      frequency of extreme rainfall events are likely to drive changes in the
      populations of these species through direct and indirect changes in predation
      pressure and wildfires.

PMID- 23170203
TI  - Small-scale resource tracking in a population of a long-lived insect.
AB  - How plant-feeding insects distribute themselves and utilize their host plant
      resources is still poorly understood. Several processes may be involved, and
      their relative roles may vary with the spatial scale considered. Herein, we
      investigate small-scale patterns, namely how population density of a gall midge
      is affected by individual growth form, phenology, and microsite characteristics
      of its herb host. The long-lived plant individuals vary much with regard to
      number of shoots, flower abundance, and flowering phenology. This variation is
      connected to site characteristics, primarily the degree of sun exposure. The
      monophagous insect galls the flowers of the host plant - an easily defined food
      resource. It is a poor disperser, but very long-lived; diapausing larvae can stay
      in the soil for many years. Galls were censused on individual plants during 5
      years; from a peak to a low in gall population density. Only a very small
      fraction of the flowers produced (<0.5%) were galled even in the peak year.
      Nevertheless, most plant individuals had galls at least 1 year. In a stepwise
      multiple regression, plant size (number of shoots) was found to be the most
      important predictor of gall density (galls/flower). However, gall density
      decreased more than one order of magnitude over the plant size range observed.
      There was also a weak effect of plant phenology. Early flowering plants had lower
      gall densities than those starting later. Sun exposure had no direct effect on
      gall density, but a path analysis revealed indirect effects via the timing of
      flowering. Gall population change was highly synchronous in different parts of
      the study area with no significant decrease in synchrony with distance.

PMID- 23170204
TI  - Genetic structure along an altitudinal gradient in Lippia origanoides, a
      promising aromatic plant species restricted to semiarid areas in northern South
      America.
AB  - The genetic diversity and population structure of Lippia origanoides, a species
      of the Verbenaceae family that shows promise as a crop plant, was investigated
      along an altitudinal gradient in the basin of the Chicamocha River in
      northeastern Colombia. The economic importance of the species, quality of its
      essential oils, and the fact that it is restricted to some few semiarid areas in
      northern South America may put the species at risk in a scenario of uncontrolled
      harvest of natural populations. Lippia origanoides was sampled along an
      altitudinal gradient from 365 to 2595 m.a.s.l. throughout Chicamocha River
      Canyon, a semiarid area in northeastern Colombia. Genetic diversity was assessed
      by means of AFLP markers. The number of AFLP loci (355) and the number of
      individuals sampled (173) were sufficient to reliably identify four populations
      at contrasting altitudes (F(ST) = 0.18, P-value < 0.0000), two populations in the
      lower basin, one population in the medium basin, and one population in the upper
      basin, with a low level of admixture between them. In average, genetic diversity
      within populations was relatively high (Ht = 0.32; I = 0.48); nevertheless,
      diversity was significantly reduced at higher altitude, a pattern that may be
      consistent with a scenario of range expansion toward higher elevations in an
      environment with more extreme conditions. The differences in altitude among the
      basins in the Chicamocha River seem to be relevant in determining the genetic
      structure of this species.

PMID- 23170205
TI  - Rainfall seasonality and pest pressure as determinants of tropical tree species'
      distributions.
AB  - Drought and pests are primary abiotic and biotic factors proposed as selective
      filters acting on species distributions along rainfall gradients in tropical
      forests and may contribute importantly to species distributional limits,
      performance, and diversity gradients. Recent research demonstrates linkages
      between species distributions along rainfall gradients and physiological drought
      tolerance; corresponding experimental examinations of the contribution of pest
      pressure to distributional limits and potential interactions between drought and
      herbivory are limited. This study aims to quantitate differential performance and
      herbivory as a function of species range limits across a climatic and floristic
      transition in Southeast Asia. Khao Chong Botanical Garden, Thailand and Pasoh
      Forest Reserve, Malaysia straddle the Kangar-Pattani Line. A reciprocal
      transplantation across a seasonality gradient was established using two groups of
      species ("widespread" taxa whose distributions include seasonally dry forests and
      "aseasonal" taxa whose distributions are limited to aseasonal forests). Growth,
      biomass allocation, survival, and herbivory were monitored for 19 months.
      Systematic differences in performance were a function of species distribution in
      relation to rainfall seasonality. In aseasonal Pasoh, aseasonal species had both
      greater growth and survivorship than widespread species. These differences were
      not a function of differential herbivory as widespread and aseasonal species
      experienced similar damage in the aseasonal forest. In seasonally dry Khao Chong,
      widespread species showed higher survivorship than aseasonal species, but these
      differences were only apparent during drought. We link this differential
      performance to physiological mechanisms as well as differential tolerance of
      biotic pressure during drought stress. Systematic decreases in seedling survival
      in aseasonal taxa during drought corresponded with previously documented
      physiological differences and may be exacerbated by herbivore damage. These
      results have important implications for tropical diversity and community
      composition in light of predicted increases in the frequency and severity of
      drought in hyperdiverse tropical forests.

PMID- 23170206
TI  - Acclimation and interaction between drought and elevated UV-B in A. thaliana:
      Differences in response over treatment, recovery and reproduction.
AB  - Here, a factorial experiment was used to investigate the interactive effects of a
      UV-B episode and concurrent progressive drought on the growth, chemistry, and
      reproductive success of A. thaliana. Both drought and UV-B negatively affected
      rosette growth, although UV-B had the greater effect. Acclimation to UV-B
      involved adjustment of leaf morphology, while drought induced accumulation of
      soluble sugars and phenolics. All plants recovered from treatments, but the cost
      of recovery was a developmental delay resulting in alteration in phenological
      timings. Combined treatments interacted causing additive negative effects on
      growth following exposure. This may be linked with inhibition of soluble sugar
      accumulation by UV-B, restricting the capacity for osmotic adjustment in response
      to drought. Following cessation of treatments, relative growth rate (RGR) and net
      assimilation rate (NAR) were significantly stimulated in plants treated with
      combined drought and UV-B. This interaction alleviated subsequent impacts of
      elevated UV-B on silique yield and reproductive timings. This study demonstrates
      the potential for interaction between these two common environmental factors.
      Furthermore, it shows the changeable nature of these interactions over the course
      of exposure and recovery through to reproduction, highlighting the need for
      sustained assessment of such interactions over a plant's lifecycle.

PMID- 23170207
TI  - Historical demographic dynamics underlying local adaptation in the presence of
      gene flow.
AB  - The range of a species is the result of the relative contribution of spatial
      tracking of environmental requirements and adaptation to ecological conditions
      outside the ancestral niche. The appearance of novel habitats caused by climatic
      oscillation can promote range expansion and accompanying demographic growth. The
      demographic dynamics of populations leave a signal in ? patterns. We modeled
      three competing scenarios pertaining to the circumstance of a range expansion by
      the Karoo Scrub-Robin into newly available habitat resulting from the increasing
      aridification of southern Africa. Genetic variation was contrasted with the
      theoretical expectations of a spatial range expansion, and compared with data of
      a putative adaptive trait. We infer that this bird likely colonized the arid
      zone, as a consequence of adaptive evolution in a small peripheral population,
      followed by an expansion with recurrent exchange of migrants with the ancestral
      populations.

PMID- 23170208
TI  - Effect of latitudinal gradient and impact of logging on genetic diversity of
      Cedrela lilloi along the Argentine Yungas Rainforest.
AB  - Cedrela lilloi C. DC. (cedro coya, Meliaceae), an important south American timber
      species, has been historically overexploited through selective logging in
      Argentine Yungas Rainforest. Management and conservation programs of the species
      require knowledge of its genetic variation patterns; however, no information is
      available. Molecular genetic variability of the species was characterized to
      identify high-priority populations for conservation and domestication purposes.
      Fourteen native populations (160 individuals) along a latitudinal gradient and
      with different logging's intensities were assessed by 293 polymorphic AFLP
      (amplified fragment length polymorphism) markers. Genetic diversity was low (Ht =
      0.135), according to marginal location of the species in Argentina. Most of the
      diversity was distributed within populations (87%). Northern populations showed
      significant higher genetic diversity (R(2)= 0.69) that agreed with latitudinal
      pattern of distribution of taxonomic diversity in the Yungas. Three clusters were
      identified by Bayesian analysis in correspondence with northern, central, and
      southern Yungas. An analysis of molecular variance (AMOVA) revealed significant
      genetic differences among latitudinal clusters even when logging (Phi(RT) = 0.07)
      and unlogging populations (Phi(PT) = 0.10) were separately analyzed. Loss of
      genetic diversity with increasing logging intensity was observed between
      neighboring populations with different disturbance (Phi(PT) = 0.03-0.10).
      Bottlenecks in disturbed populations are suggested as the main cause. Our results
      emphasize both: the necessity of maintaining the genetic diversity in protected
      areas that appear as possible long-term refuges of the species; and to rescue for
      the national system of protected areas some high genetic diversity populations
      that are on private fields.

PMID- 23170209
TI  - Genomic variation in cline shape across a hybrid zone.
AB  - Hybrid zones are unique biological interfaces that reveal both population level
      and species level evolutionary processes. A genome-scale approach to assess gene
      flow across hybrid zones is vital, and now possible. In Mexican towhees (genus
      Pipilo), several morphological hybrid gradients exist. We completed a genome
      survey across one such gradient (9 populations, 140 birds) using mitochondrial
      DNA, 28 isozyme, and 377 AFLP markers. To assess variation in introgression among
      loci, cline parameters (i.e., width, center) for the 61 clinally varying loci
      were estimated and compiled into genomic distributions for tests against three
      empirical models spanning the range of observed cline shape. No single model
      accounts for observed variation in cline shape among loci. Numerous backcross
      individuals near the gradient center confirm a hybrid origin for these
      populations, contrary to a previous hypothesis based on social mimicry and
      character displacement. In addition, the observed variation does not bin into
      well-defined categories of locus types (e.g., neutral vs. highly selected). Our
      multi-locus analysis reveals cross-genomic variation in selective constraints on
      gene flow and locus-specific flexibility in the permeability of the interspecies
      membrane.

PMID- 23170210
TI  - Genetic diversity and geographic distribution of Bemisia tabaci (Gennadius)
      (Hemiptera: Aleyrodidae) genotypes associated with cassava in East Africa.
AB  - The genetic variability of whitefly (Bemisia tabaci) species, the vectors of
      cassava mosaic begomoviruses (CMBs) in cassava growing areas of Kenya, Tanzania,
      and Uganda, was investigated through comparison of partial sequences of the
      mitochondria cytochrome oxidase I (mtCOI) DNA in 2010/11. Two distinct species
      were obtained including sub-Saharan Africa 1 (SSA1), comprising of two sub-clades
      (I and II), and a South West Indian Ocean Islands (SWIO) species. Among the SSA1,
      sub-clade I sequences shared a similarity of 97.8-99.7% with the published Uganda
      1 genotypes, and diverged by 0.3-2.2%. A pairwise comparison of SSA1 sub-clade II
      sequences revealed a similarity of 97.2-99.5% with reference southern Africa
      genotypes, and diverged by 0.5-2.8%. The SSA1 sub-clade I whiteflies were widely
      distributed in East Africa (EA). In comparison, the SSA1 sub-clade II whiteflies
      were detected for the first time in the EA region, and occurred predominantly in
      the coast regions of Kenya, southern and coast Tanzania. They occurred in low
      abundance in the Lake Victoria Basin of Tanzania and were widespread in all four
      regions in Uganda. The SWIO species had a sequence similarity of 97.2-97.7% with
      the published Reunion sequence and diverged by 2.3-2.8%. The SWIO whiteflies
      occurred in coast Kenya only. The sub-Saharan Africa 2 whitefly species (Ug2)
      that was associated with the severe CMD pandemic in Uganda was not detected in
      our study.

PMID- 23170211
TI  - Fine-scale selection by ovipositing females increases egg survival.
AB  - One of the most important defenses for the eggs of ovipositing female organisms
      is to avoid being laid in the same habitat as their predators. However, for most
      organisms, completely avoiding an offspring's predators is not possible. One
      mechanism that has been largely overlooked is for females to partition an
      oviposition site into microhabitats that differ in quality for offspring
      survival. We conducted a series of experiments to examine whether female newts
      avoid microhabitats utilized by their offspring's primary predator, caddisfly
      larvae. Female newts avoided laying eggs near predatory caddisflies and shifted
      egg laying upward in the water column when provided with a vertical dimension.
      Caddisflies were attracted to chemical stimuli from female newts and their eggs,
      yet primarily used benthic areas in experimental chambers. Finally, results from
      a field experiment indicate that the behavioral strategy employed by female newts
      increases offspring survival. This subset of non-genetic maternal effects, micro
      oviposition avoidance, is likely an important yet underexplored mechanism by
      which females increase offspring survival.

PMID- 23170212
TI  - Philopatry drives genetic differentiation in an island archipelago: comparative
      population genetics of Galapagos Nazca boobies (Sula granti) and great
      frigatebirds (Fregata minor).
AB  - Seabirds are considered highly mobile, able to fly great distances with few
      apparent barriers to dispersal. However, it is often the case that seabird
      populations exhibit strong population genetic structure despite their potential
      vagility. Here we show that Galapagos Nazca booby (Sula granti) populations are
      substantially differentiated, even within the small geographic scale of this
      archipelago. On the other hand, Galapagos great frigatebird (Fregata minor)
      populations do not show any genetic structure. We characterized the genetic
      differentiation by sampling five colonies of both species in the Galapagos
      archipelago and analyzing eight microsatellite loci and three mitochondrial
      genes. Using an F-statistic approach on the multilocus data, we found significant
      differentiation between nearly all island pairs of Nazca booby populations and a
      Bayesian clustering analysis provided support for three distinct genetic
      clusters. Mitochondrial DNA showed less differentiation of Nazca booby colonies;
      only Nazca boobies from the island of Darwin were significantly differentiated
      from individuals throughout the rest of the archipelago. Great frigatebird
      populations showed little to no evidence for genetic differentiation at the same
      scale. Only two island pairs (Darwin - Wolf, N. Seymour - Wolf) were
      significantly differentiated using the multilocus data, and only two island pairs
      had statistically significant phi(ST) values (N. Seymour - Darwin, N. Seymour -
      Wolf) according to the mitochondrial data. There was no significant pattern of
      isolation by distance for either species calculated using both markers. Seven of
      the ten Nazca booby migration rates calculated between island pairs were in the
      south or southeast to north or northwest direction. The population
      differentiation found among Galapagos Nazca booby colonies, but not great
      frigatebird colonies, is most likely due to differences in natal and breeding
      philopatry.

PMID- 23170213
TI  - A fecundity cost of (walking) mobility in an insect.
AB  - Evolutionary theory predicts trade-offs between fecundity and mobility, but there
      is substantial lack of empirical evidence if and how basic mobility relates to
      fitness costs. In a field experiment, we investigated fecundity costs of mobility
      in a non-migratory, wing-monomorphic grasshopper, Stenobothrus lineatus, and at
      the same time tested for possible effects of reproductive state (egg-load) on the
      mobility. For 10 days, body weight and activity radius of 60 females were
      recorded daily and oviposition events were inferred from abrupt weight losses. We
      found a strong and significant relationship between the individual mobility and
      the time between egg pods laid (interpod period). Individual egg-laying was
      reduced by a rate of 0.36 eggs per day with each meter increase in mean daily
      activity radius. The trade-off was not biased by the size of the females, that
      is, constitution did not positively influence both offspring number and mobility.
      Egg-load had no significant influence on the individual distances travelled. We
      could demonstrate that mobility - as induced and selected for by foraging,
      thermoregulation, predator escape, shelter seeking, and reproduction - can be
      directly paid off by fecundity. This direct consequence of mobility on individual
      fitness was detected for the first time in a walking insect.

PMID- 23170214
TI  - Seasonal population dynamics and the genetic structure of the mosquito vector
      Aedes aegypti in Sao Paulo, Brazil.
AB  - Population genetic studies of insect vectors can generate knowledge to improve
      epidemiological studies focused on the decrease of pathogen transmission. In this
      study, we used nine SNPs across the Aedes aegypti genome to characterize seasonal
      population variations of this important dengue vector. Mosquito samples were
      obtained by ovitraps placed over Botucatu SP from 2005 to 2010. Our data show
      that, regardless of the large variation in mosquito abundance (deduced from the
      number of eggs obtained from ovitraps), the effective population size remained
      stable over the years. These results suggest that Ae. aegypti is able to maintain
      a sufficiently large active breeding population during the dry season to keep
      genetic frequencies stable. These results open new perspectives on mosquito
      survey and control methods.

PMID- 23170215
TI  - Biogeographic models of gene flow in two waterfowl of the Australo-Papuan
      tropics.
AB  - There are many large, easy-to-observe anseriform birds (ducks, geese, and swans)
      in northern Australia and New Guinea and they often gather in large numbers. Yet,
      the structure of their populations and their regional movements are poorly
      understood. Lack of understanding of population structure limits our capacity to
      understand source-sink dynamics relevant to their conservation or assess risks
      associated with avian-borne pathogens, in particular, avian influenza for which
      waterfowl are the main reservoir species. We set out to assess present-day
      genetic connectivity between populations of two widely distributed waterfowl in
      the Australo-Papuan tropics, magpie goose Anseranas semipalmata (Latham, 1798)
      and wandering whistling-duck Dendrocygna arcuata (Horsfield, 1824).
      Microsatellite data were obtained from 237 magpie geese and 64 wandering
      whistling-duck. Samples were collected across northern Australia, and at one site
      each in New Guinea and Timor Leste. In the wandering whistling-duck, genetic
      diversity was significantly apportioned by region and sampling location. For this
      species, the best model of population structure was New Guinea as the source
      population for all other populations. One remarkable result for this species was
      genetic separation of two flocks sampled contemporaneously on Cape York Peninsula
      only a few kilometers apart. In contrast, evidence for population structure was
      much weaker in the magpie goose, and Cape York as the source population provided
      the best fit to the observed structure. The fine scale genetic structure observed
      in wandering whistling-duck and magpie goose is consistent with earlier
      suggestions that the west-coast of Cape York Peninsula is a flyway for Australo
      Papuan anseriforms between Australia and New Guinea across Torres Strait.

PMID- 23170216
TI  - Habitat selection and ranges of tolerance: how do species differ beyond critical
      thresholds?
AB  - Sensitivity to habitat fragmentation often has been examined in terms of
      thresholds in landscape composition at which a species is likely to occur.
      Observed thresholds often have been low or absent, however, leaving much
      unexplained about habitat selection beyond initial thresholds of occurrence, even
      for species with strong habitat preferences. We examined responses to varying
      amounts of tree cover, a widely influential measure of habitat loss, for 40
      woodland bird species in a mixed woodland/grassland landscape in eastern North
      Dakota, USA. We used LOESS smoothing to describe incidence for each species at
      three scales: within 200, 400, and 1200 m around sample locations. For the 200-m
      scale, we also calculated the most-preferred range of tree cover (within which at
      least half of observations were predicted to occur) for each species. Only 10 of
      40 species had occurrence thresholds greater than about 10% tree cover. After
      initial occurrence, species showed three general patterns: some increased
      monotonically with tree cover; some increased up to an asymptote; some peaked at
      intermediate amounts of tree cover and then declined. These patterns approximate
      selection for interior woodlands and for edge-rich environments, but incidence
      plots provide greater detail in landscape-scale selection than do those
      categories. For most species, patterns persisted at larger scales, but for some,
      larger scales had distinctly different patterns than local scales. Preferred
      ranges of tree cover varied from <20% tree cover (common grackle, Quiscalus
      quiscula) to >60% (veery, Catharus fuscescens). We conclude that incidence
      patterns provide more information on habitat selection than do threshold measures
      for most species: in particular, they differentiate species preferring
      concentrated woodlands from those preferring mixed landscapes, and they show
      contrasting degrees of selectiveness. [Correction added on 16 October 2012, after
      first online publication: the Abstract section has been reworded].

PMID- 23170217
TI  - Primate DNA suggests long-term stability of an African rainforest.
AB  - Red colobus monkeys, due to their sensitivity to environmental change, are
      indicator species of the overall health of their tropical rainforest habitats. As
      a result of habitat loss and overhunting, they are among the most endangered
      primates in the world, with very few viable populations remaining. Traditionally,
      extant indicator species have been used to signify the conditions of their
      current habitats, but they have also been employed to track past environmental
      conditions by detecting previous population fluctuations. Kibale National Park
      (KNP) in Uganda harbors the only remaining unthreatened large population of red
      colobus. We used microsatellite DNA to evaluate the historical demography of
      these red colobus and, therefore, the long-term stability of their habitat. We
      find that the red colobus population throughout KNP has been stable for at least
      ~40,000 years. We interpret this result as evidence of long-term forest stability
      because a change in the available habitat or population movement would have
      elicited a corresponding change in population size. We conclude that the forest
      of what is now Kibale National Park may have served as a Late Pleistocene refuge
      for many East African species.

PMID- 23170218
TI  - Physico-chemical variables determining the invasion risk of freshwater habitats
      by alien mollusks and crustaceans.
AB  - The aim of this study was to assess the invasion risk of freshwater habitats and
      determine the environmental variables that are most favorable for the
      establishment of alien amphipods, isopods, gastropods, and bivalves. A total of
      981 sites located in streams and rivers in Germany. Therefore we analyzed
      presence-absence data of alien and indigenous amphipods, isopods, gastropods, and
      bivalves from 981 sites located in small to large rivers in Germany with regard
      to eight environmental variables: chloride, ammonium, nitrate, oxygen,
      orthophosphate, distance to the next navigable waterway, and maximum and minimum
      temperature. Degraded sites close to navigable waters were exposed to an
      increased invasion risk by all major groups of alien species. Moreover, invaded
      sites by all four groups of alien species were similar, whereas the sites where
      indigenous members of the four groups occurred were more variable. Increased
      temperature and chloride concentration as well as decreased oxygen concentration
      were identified as major factors for the invasibility of a site. Species-specific
      analyses showed that chloride was among the three most predictive environmental
      variables determining species assemblage in all four taxonomic groups. Also
      distance to the next navigable waterways was similarly important. Additionally,
      the minimum temperature was among the most important variables for amphipods,
      isopods, and bivalves. The bias in the occurrence patterns of alien species
      toward similarly degraded habitats suggests that the members of all four major
      groups of freshwater alien species are a non-random, more tolerant set of
      species. Their common tolerance to salinity, high temperature, and oxygen
      depletion may reflect that most alien species were spread in ballast water tanks,
      where strong selective pressures, particularly temperature fluctuations, oxygen
      depletion, and increased salinity may create a bottleneck for successful
      invasion. Knowledge on the major factors that influence the invasion risk of a
      habitat is needed to develop strategies to limit the spread of invasive species.

PMID- 23170219
TI  - Warming off southwestern Japan linked to distributional shifts of subtidal canopy
      forming seaweeds.
AB  - To assess distributional shifts of species in response to recent warming,
      historical distribution records are the most requisite information. The surface
      seawater temperature (SST) of Kochi Prefecture, southwestern Japan on the western
      North Pacific, has significantly risen, being warmed by the Kuroshio Current.
      Past distributional records of subtidal canopy-forming seaweeds (Laminariales and
      Fucales) exist at about 10-year intervals from the 1970s, along with detailed SST
      datasets at several sites along Kochi's >700 km coastline. In order to provide a
      clear picture of distributional shifts of coastal marine organisms in response to
      warming SST, we observed the present distribution of seaweeds and analyzed the
      SST datasets to estimate spatiotemporal SST trends in this coastal region. We
      present a large increase of 0.3 degrees C/decade in the annual mean SST of this
      area over the past 40 years. Furthermore, a comparison of the previous and
      present distributions clearly showed the contraction of temperate species'
      distributional ranges and expansion of tropical species' distributional ranges in
      the seaweeds. Although the main temperate kelp Ecklonia (Laminariales) had
      expanded their distribution during periods of cooler SST, they subsequently
      declined as the SST warmed. Notably, the warmest SST of the 1997-98 El Nino
      Southern Oscillation event was the most likely cause of a widespread destruction
      of the kelp populations; no recovery was found even in the present survey at the
      formerly habitable sites where warm SSTs have been maintained. Temperate
      Sargassum spp. (Fucales) that dominated widely in the 1970s also declined in
      accordance with recent warming SSTs. In contrast, the tropical species, S.
      ilicifolium, has gradually expanded its distribution to become the most
      conspicuously dominant among the present observations. Thermal gradients, mainly
      driven by the warming Kuroshio Current, are presented as an explanation for the
      successive changes in both temperate and tropical species' distributions.

PMID- 23170220
TI  - Keeping pace with climate change: what is wrong with the evolutionary potential
      of upper thermal limits?
AB  - The potential of populations to evolve in response to ongoing climate change is
      partly conditioned by the presence of heritable genetic variation in relevant
      physiological traits. Recent research suggests that Drosophila melanogaster
      exhibits negligible heritability, hence little evolutionary potential in heat
      tolerance when measured under slow heating rates that presumably mimic conditions
      in nature. Here, we study the effects of directional selection for increased heat
      tolerance using Drosophila as a model system. We combine a physiological model to
      simulate thermal tolerance assays with multilocus models for quantitative traits.
      Our simulations show that, whereas the evolutionary response of the genetically
      determined upper thermal limit (CTmax) is independent of methodological context,
      the response in knockdown temperatures varies with measurement protocol and is
      substantially (up to 50%) lower than for CTmax. Realized heritabilities of
      knockdown temperature may grossly underestimate the true heritability of CTmax.
      For instance, assuming that the true heritability of CTmax in the base population
      is h(2) = 0.25, realized heritabilities of knockdown temperature are around 0.08
      0.16 depending on heating rate. These effects are higher in slow heating assays,
      suggesting that flawed methodology might explain the apparently limited
      evolutionary potential of cosmopolitan D. melanogaster.

PMID- 23170221
TI  - A Geographic Information Systems (GIS)-based analysis of modern South African
      rodent distributions, habitat use, and environmental tolerances.
AB  - GOALS OF THIS STUDY WERE TO: (1) develop distributional maps of modern rodent
      genera throughout the countries of South Africa, Lesotho, and Swaziland by
      georeferencing museum specimens; (2) assess habitat preferences for genera by
      cross-referencing locality position with South African vegetation; and (3)
      identify mean annual precipitation and temperature range where the genera are
      located. Conterminous South Africa including the countries of Lesotho and
      Swaziland Digital databases of rodent museum specimens housed in the Ditsong
      National Museum of Natural History, South Africa (DM), and the Division of
      Mammals, National Museum of Natural History, Smithsonian Institution, United
      States (NMNH), were acquired and then sorted into a subset of specimens with
      associated coordinate data. The coordinate data were then used to develop
      distributional maps for the rodent genera present within the study area. Percent
      habitat occupation and descriptive statistics for six climatic variables were
      then determined for each genus by cross-referencing locality positions with
      vegetation and climatic maps. This report presents a series of maps illustrating
      the distribution of 35 rodent genera based on 19,471 geo-referenced specimens
      obtained from two major collections. Inferred habitat use by taxon is provided
      for both locality and specimen percent occurrence at three hierarchical habitat
      levels: biome, bioregion, and vegetation unit. Descriptive statistics for six
      climatic variables are also provided for each genus based on locality and
      specimen percent incidence. As rodent faunas are commonly used in
      paleoenvironmental reconstructions, an accurate assessment of rodent
      environmental tolerance ranges is necessary before confidence can be placed in an
      actualistic model. While the data presented here represent only a subset of the
      modern geographic distributions for many of the taxa examined, a wide range of
      environmental regimes are observed, suggesting that more research is necessary in
      order to accurately reconstruct an environmental signature when these taxa are
      found in the fossil record.

PMID- 23170222
TI  - Gene flow on ice: the role of sea ice and whaling in shaping Holarctic genetic
      diversity and population differentiation in bowhead whales (Balaena mysticetus).
AB  - Sea ice is believed to be a major factor shaping gene flow for polar marine
      organisms, but it remains unclear to what extent it represents a true barrier to
      dispersal for arctic cetaceans. Bowhead whales are highly adapted to polar sea
      ice and were targeted by commercial whalers throughout Arctic and subarctic seas
      for at least four centuries, resulting in severe reductions in most areas. Both
      changing ice conditions and reductions due to whaling may have affected
      geographic distribution and genetic diversity throughout their range, but little
      is known about range-wide genetic structure or whether it differed in the past.
      This study represents the first examination of genetic diversity and
      differentiation across all five putative stocks, including Baffin Bay-Davis
      Strait, Hudson Bay-Foxe Basin, Bering-Beaufort-Chukchi, Okhotsk, and Spitsbergen.
      We also utilized ancient specimens from Prince Regent Inlet (PRI) in the Canadian
      Arctic and compared them with modern stocks. Results from analysis of molecular
      variance and demographic simulations are consistent with recent and high gene
      flow between Atlantic and Pacific stocks in the recent past. Significant genetic
      differences between ancient and modern populations suggest PRI harbored unique
      maternal lineages in the past that have been recently lost, possibly due to loss
      of habitat during the Little Ice Age and/or whaling. Unexpectedly, samples from
      this location show a closer genetic relationship with modern Pacific stocks than
      Atlantic, supporting high gene flow between the central Canadian Arctic and
      Beaufort Sea over the past millennium despite extremely heavy ice cover over much
      of this period.

PMID- 23170226
TI  - The soluble pyocins S2 and S4 from Pseudomonas aeruginosa bind to the same FpvAI
      receptor.
AB  - Soluble (S-type) pyocins are Pseudomonas aeruginosa bacteriocins that kill
      nonimmune P. aeruginosa cells by gaining entry via a specific receptor, which, in
      the case of pyocin S2, is the siderophore pyoverdine receptor FpvAI, and in the
      case of pyocin S3, FpvAII. The nucleic acid sequence at the positions 4327697
      4327359 of P. aeruginosa PAO1 genome was not annotated, but it was predicted to
      encode the immunity gene of the flanking pyocin S4 gene (PA3866) based on our
      analysis of the genome sequence. Using RT-PCR, the expression of the immunity
      gene was detected, confirming the existence of an immunity gene overlapping the
      S4 pyocin gene. The PA3866 coding for pyocin S4 and the downstream gene coding
      for the immunity protein were cloned and expressed in Escherichia coli and the
      His-tagged S4 pyocin was obtained in pure form. Forty-three P. aeruginosa strains
      were typed via PCR to identify their ferripyoverdine receptor gene (fpvAI-III)
      and were tested for their sensitivity to pyocin S4. All S4-sensitive strains had
      the type I ferripyoverdine receptor fpvA gene. Some S4-resistant type I fpvA
      positive strains were detected, but all of them had the S4 immunity gene, and,
      following the deletion of the immunity gene, became S4-sensitive. The fpvAI
      receptor gene was deleted in a S4-sensitive strain, and, as expected, the mutant
      became resistant to S4. The N-terminal receptor binding domain (RBD) of pyocin
      S2, which also uses the FpvAI receptor to enter the cell, was cloned in the pET
      15b vector, and expressed in E. coli. When the purified RBD was mixed with pyocin
      S4 at different ratios, an inhibition of killing was observed, indicating that S2
      RBD competes with the pyocin S4 for the binding to the FpvAI receptor. The S2 RBD
      was also shown to enhance the expression of the pvdA pyoverdine gene, suggesting
      that it, like pyoverdine, works via the known siderophore-mediated signalization
      pathway.

PMID- 23170223
TI  - Transposable elements and viruses as factors in adaptation and evolution: an
      expansion and strengthening of the TE-Thrust hypothesis.
AB  - In addition to the strong divergent evolution and significant and episodic
      evolutionary transitions and speciation we previously attributed to TE-Thrust, we
      have expanded the hypothesis to more fully account for the contribution of
      viruses to TE-Thrust and evolution. The concept of symbiosis and holobiontic
      genomes is acknowledged, with particular emphasis placed on the creativity
      potential of the union of retroviral genomes with vertebrate genomes. Further
      expansions of the TE-Thrust hypothesis are proposed regarding a fuller account of
      horizontal transfer of TEs, the life cycle of TEs, and also, in the case of a
      mammalian innovation, the contributions of retroviruses to the functions of the
      placenta. The possibility of drift by TE families within isolated demes or
      disjunct populations, is acknowledged, and in addition, we suggest the
      possibility of horizontal transposon transfer into such subpopulations. "Adaptive
      potential" and "evolutionary potential" are proposed as the extremes of a
      continuum of "intra-genomic potential" due to TE-Thrust. Specific data is given,
      indicating "adaptive potential" being realized with regard to insecticide
      resistance, and other insect adaptations. In this regard, there is agreement
      between TE-Thrust and the concept of adaptation by a change in allele
      frequencies. Evidence on the realization of "evolutionary potential" is also
      presented, which is compatible with the known differential survivals, and
      radiations of lineages. Collectively, these data further suggest the possibility,
      or likelihood, of punctuated episodes of speciation events and evolutionary
      transitions, coinciding with, and heavily underpinned by, intermittent bursts of
      TE activity.

PMID- 23170225
TI  - Multiplicity of Salmonella entry mechanisms, a new paradigm for Salmonella
      pathogenesis.
AB  - The Salmonella enterica species includes about 2600 diverse serotypes, most of
      which cause a wide range of food- and water-borne diseases ranging from self
      limiting gastroenteritis to typhoid fever in both humans and animals. Moreover,
      some serotypes are restricted to a few animal species, whereas other serotypes
      are able to infect plants as well as cold- and warm-blooded animals. An essential
      feature of the pathogenicity of Salmonella is its capacity to cross a number of
      barriers requiring invasion of a large variety of phagocytic and nonphagocytic
      cells. The aim of this review is to describe the different entry pathways used by
      Salmonella serotypes to enter different nonphagocytic cell types. Until recently,
      it was accepted that Salmonella invasion of eukaryotic cells required only the
      type III secretion system (T3SS) encoded by the Salmonella pathogenicity island
      1. However, recent evidence shows that Salmonella can cause infection in a T3SS-1
      independent manner. Currently, two outer membrane proteins Rck and PagN have been
      clearly identified as Salmonella invasins. As Rck mediates a Zipper-like entry
      mechanism, Salmonella is therefore the first bacterium shown to be able to induce
      both Zipper and Trigger mechanisms to invade host cells. In addition to these
      known entry pathways, recent data have shown that unknown entry routes could be
      used according to the serotype, the host and the cell type considered, inducing
      either Zipper-like or Trigger-like entry processes. The new paradigm presented
      here should change our classic view of Salmonella pathogenicity. It could also
      modify our understanding of the mechanisms leading to the different Salmonella
      induced diseases and to Salmonella-host specificity.

PMID- 23170227
TI  - Prevalence of diarrheagenic Escherichia coli virulence genes in the feces of
      slaughtered cattle, chickens, and pigs in Burkina Faso.
AB  - We investigated the prevalence of the virulence genes specific for five major
      pathogroups of diarrheagenic Escherichia coli (DEC) in primary cultures from
      feces of animals slaughtered for human consumption in Burkina Faso. For the
      study, 704 feces samples were collected from cattle (n = 304), chickens (n =
      350), and pigs (n = 50) during carcass processing. The presence of the virulence
      associated genes in the mixed bacterial cultures was assessed using 16-plex
      polymerase chain reaction (PCR). Virulence genes indicating presence of DEC were
      detected in 48% of the cattle, 48% of the chicken, and 68% of the pig feces
      samples. Virulence genes specific for different DECs were detected in the
      following percentages of the cattle, chicken, and pig feces samples: Shiga toxin
      producing E. coli (STEC) in 37%, 6%, and 30%; enteropathogenic E. coli (EPEC) in
      8%, 37%, and 32%; enterotoxigenic E. coli (ETEC) in 4%, 5%, and 18%; and
      enteroaggregative E. coli (EAEC) in 7%, 6%, and 32%. Enteroinvasive E. coli
      (EIEC) virulence genes were detected in 1% of chicken feces samples only. The
      study was the first of its kind in Burkina Faso and revealed the common
      occurrence of the diarrheal virulence genes in feces of food animals. This
      indicates that food animals are reservoirs of DEC that may contaminate meat
      because of the defective slaughter and storage conditions and pose a health risk
      to the consumers in Burkina Faso.

PMID- 23170228
TI  - Rad59 regulates association of Rad52 with DNA double-strand breaks.
AB  - Homologous recombination among repetitive sequences is an important mode of DNA
      repair in eukaryotes following acute radiation exposure. We have developed an
      assay in Saccharomyces cerevisiae that models how multiple DNA double-strand
      breaks form chromosomal translocations by a nonconservative homologous
      recombination mechanism, single-strand annealing, and identified the Rad52
      paralog, Rad59, as an important factor. We show through genetic and molecular
      analyses that Rad59 possesses distinct Rad52-dependent and -independent
      functions, and that Rad59 plays a critical role in the localization of Rad52 to
      double-strand breaks. Our analysis further suggests that Rad52 and Rad59 act in
      multiple, sequential processes that determine genome structure following acute
      exposure to DNA damaging agents.

PMID- 23170229
TI  - An activator for pyruvoyl-dependent l-aspartate alpha-decarboxylase is conserved
      in a small group of the gamma-proteobacteria including Escherichia coli.
AB  - In bacteria, beta-alanine is formed via the action of l-aspartate alpha
      decarboxylase (PanD) which is one of the small class of pyruvoyl-dependent
      enzymes. The pyruvoyl cofactor in these enzymes is formed via the intramolecular
      rearrangement of a serine residue in the peptide backbone leading to chain
      cleavage and formation of the covalently-bound cofactor from the serine residue.
      This reaction was previously thought to be uncatalysed. Here we show that in
      Escherichia coli, PanD is activated by the putative acetyltransferase YhhK,
      subsequently termed PanZ. Activation of PanD both in vivo and in vitro is PanZ
      dependent. PanZ binds to PanD, and we demonstrate that a PanZ(N45A) site-directed
      mutant is unable to enhance cleavage of the proenzyme PanD despite retaining
      affinity for PanD. This suggests that the putative acetyltransferases domain of
      PanZ may be responsible for activation to enhance the processing of PanD.
      Although panD is conserved among most bacteria, the panZ gene is conserved only
      in E. coli-related enterobacterial species including Shigella, Salmonella,
      Klebsiella and Yersinia. These bacteria are found predominantly in the gut flora
      where pantothenate is abundant and regulation of PanD by PanZ allows these
      organisms to closely regulate production of beta-alanine and hence pantothenate
      in response to metabolic demand.

PMID- 23170230
TI  - Iron-regulated metabolites produced by Pseudomonas fluorescens WCS374r are not
      required for eliciting induced systemic resistance against Pseudomonas syringae
      pv. tomato in Arabidopsis.
AB  - The plant growth-promoting rhizobacterium Pseudomonas fluorescens WCS374r
      produces several iron-regulated metabolites, including the fluorescent
      siderophore pseudobactin (Psb374), salicylic acid (SA), and pseudomonine (Psm), a
      siderophore that contains a SA moiety. After purification of Psb374 from culture
      supernatant of WCS374r, its structure was determined following isoelectrofocusing
      and tandem mass spectrometry, and found to be identical to the fluorescent
      siderophore produced by P. fluorescens ATCC 13525. To study the role of SA and
      Psm production in colonization of Arabidopsis thaliana roots and in induced
      systemic resistance (ISR) against Pseudomonas syringae pv. tomato (Pst) by strain
      WCS374r, mutants disrupted in the production of these metabolites were obtained
      by homologous recombination. These mutants were further subjected to transposon
      Tn5 mutagenesis to generate mutants also deficient in Psb374 production. The
      mutants behaved similar to the wild type in both their Arabidopsis rhizosphere
      colonizing capacity and their ability to elicit ISR against Pst. We conclude that
      Psb374, SA, and Psm production by P. fluorescens WCS374r are not required for
      eliciting ISR in Arabidopsis.

PMID- 23170231
TI  - Evidence for the involvement of the anthranilate degradation pathway in
      Pseudomonas aeruginosa biofilm formation.
AB  - Bacterial biofilms are complex cell communities found attached to surfaces and
      surrounded by an extracellular matrix composed of exopolysaccharides, DNA, and
      proteins. We investigated the whole-genome expression profile of Pseudomonas
      aeruginosa sessile cells (SCs) present in biofilms developed on a glass wool
      substratum. The transcriptome and proteome of SCs were compared with those of
      planktonic cell cultures. Principal component analysis revealed a biofilm
      specific gene expression profile. Our study highlighted the overexpression of
      genes controlling the anthranilate degradation pathway in the SCs grown on glass
      wool for 24 h. In this condition, the metabolic pathway that uses anthranilate
      for Pseudomonas quinolone signal production was not activated, which suggested
      that anthranilate was primarily being consumed for energy metabolism. Transposon
      mutants defective for anthranilate degradation were analyzed in a simple assay of
      biofilm formation. The phenotypic analyses confirmed that P. aeruginosa biofilm
      formation partially depended on the activity of the anthranilate degradation
      pathway. This work points to a new feature concerning anthranilate metabolism in
      P. aeruginosa SCs.

PMID- 23170232
TI  - Abundance and short-term temporal variability of fecal microbiota in healthy
      dogs.
AB  - Temporal variations of intestinal microorganisms have been investigated in
      humans, but limited information is available for other animal species. The aim of
      the study was to evaluate the abundance and short-term temporal variability of
      fecal microbiota in dogs. Two fecal samples were collected (15 days apart) from
      six healthy dogs. The microbiota was evaluated using fluorescence in situ
      hybridization (FISH) and 454-pyrosequencing targeting the 16S rRNA and its gene.
      Pyrosequencing revealed 15 families comprising >80% of all microbiota, over time
      intraindividual coefficients of variation (%CV) ranged from 2% to 141% (median:
      55%). In contrast, the interindividual %CV ranged from 62% to 230% (median:
      145%). Relative proportions of Faecalibacterium (important for intestinal health)
      and Subdoligranulum were low (two dogs harbored 4-7% of Subdoligranulum, the
      remaining dogs had <1% of either genus). Conversely, FISH revealed that
      Faecalibacterium comprised a median of 5% of total counts (range: 0-8%, probe
      Fprau645). A novel FISH probe (Faecali 698) was tested that, compared with
      Fprau645, can detect in silico a similar percentage of Faecalibacterium but
      higher proportions of Subdoligranulum. This probe revealed a high percentage of
      Faecalibacterium-Subdoligranulum (median: 16% of total counts). Future studies
      should consider the observed variability and discrepancies in microbial abundance
      between FISH and 454-pyrosequencing.

PMID- 23170234
TI  - Cellular basis for singing motor pattern generation in the field cricket (Gryllus
      bimaculatus DeGeer).
AB  - The singing behavior of male crickets allows analyzing a central pattern
      generator (CPG) that was shaped by sexual selection for reliable production of
      species-specific communication signals. After localizing the essential ganglia
      for singing in Gryllus bimaculatus, we now studied the calling song CPG at the
      cellular level. Fictive singing was initiated by pharmacological brain
      stimulation. The motor pattern underlying syllables and chirps was recorded as
      alternating spike bursts of wing-opener and wing-closer motoneurons in a
      truncated wing nerve; it precisely reflected the natural calling song. During
      fictive singing, we intracellularly recorded and stained interneurons in thoracic
      and abdominal ganglia and tested their impact on the song pattern by
      intracellular current injections. We identified three interneurons of the
      metathoracic and first unfused abdominal ganglion that rhythmically de- and
      hyperpolarized in phase with the syllable pattern and spiked strictly before the
      wing-opener motoneurons. Depolarizing current injection in two of these opener
      interneurons caused additional rhythmic singing activity, which reliably reset
      the ongoing chirp rhythm. The closely intermeshing arborizations of the singing
      interneurons revealed the dorsal midline neuropiles of the metathoracic and three
      most anterior abdominal neuromeres as the anatomical location of singing pattern
      generation. In the same neuropiles, we also recorded several closer interneurons
      that rhythmically hyper- and depolarized in the syllable rhythm and spiked
      strictly before the wing-closer motoneurons. Some of them received pronounced
      inhibition at the beginning of each chirp. Hyperpolarizing current injection in
      the dendrite revealed postinhibitory rebound depolarization as one functional
      mechanism of central pattern generation in singing crickets.

PMID- 23170235
TI  - BDNF Val66Met polymorphism interacts with sex to influence bimanual motor control
      in healthy humans.
AB  - Brain-derived neurotrophic factor (BDNF) plays a critical role in brain
      development. A common single nucleotide polymorphism in the gene encoding BDNF
      (rs6265, Val66Met) affects BDNF release and has been associated with altered
      learning and memory performance, and with structural changes in brain morphology
      and corpus callosum integrity. BDNF Val66Met has more recently been shown to
      influence motor learning and performance. Some of the BDNF effects seem to be
      modulated by an individual's sex, but currently the relationship between BDNF and
      sex in the motor domain remains elusive. Here, we investigate the relationship
      between BDNF Val66Met genotype and an individual's sex in the motor system.
      Seventy-six healthy, previously genotyped, individuals performed a task in which
      the participant drew lines at different angles of varying difficulty. Subjects
      controlled the horizontal and vertical movement of the line on a computer screen
      by rotating two cylinders. We used this bimanual motor control task to measure
      contributions from both current motor function and the pre-existing
      interhemispheric connectivity. We report that BDNF genotype interacts with sex to
      influence the motor performance of healthy participants in this bimanual motor
      control task. We further report that the BDNF genotype by sex interaction was
      present in the more difficult trials only, which is in line with earlier findings
      that genetic effects may become apparent only when a system is challenged. Our
      results emphasize the importance of taking sex into account when investigating
      the role of BDNF genotype in the motor system.

PMID- 23170236
TI  - Overexpression of cyclic GMP-dependent protein kinase reduces MeCP2 and HDAC2
      expression.
AB  - Nitric oxide (NO) and the C-type natriuretic peptide (CNP) exert their action via
      stimulation of the cyclic GMP (cGMP)-signaling pathway, which includes the
      activation of cGMP-dependent protein kinases (PKG). The present report shows that
      the activation of PKG by local application of 8-bromo-cGMP in the caudate-putamen
      reduced the expression of the epigenetic markers, methyl-CpG-binding protein 2
      (MeCP2) and histone deacetylase 2 (HDAC2), in dopaminergic projection areas of
      cocaine-treated rats. An effect of lesser amplitude was observed when rats were
      not injected with cocaine. We also studied the effect of PKG overexpression by
      injecting a plasmid vector containing the human PKG-Ialpha cDNA in either the
      caudate-putamen or the ventral tegmental area. Injection in the caudate-putamen
      reduced the epigenetic parameters with higher amplitude than the cGMP analog. The
      effect was abolished by the injection of a selective PKG inhibitor, confirming
      that it was due to PKG-dependent phosphorylation. As MeCP2 and HDAC2 modulate
      dynamic functions in the adult brain such as memory formation and synaptic
      plasticity, the downregulation of expression by PKG suggests that the cGMP
      pathway affects cognitive processes through a mechanism that comprises the
      MeCP2/HDAC2 complex and the subsequent control of gene silencing.

PMID- 23170237
TI  - Effects of motivation on reward and attentional networks: an fMRI study.
AB  - Existing evidence suggests that reward and attentional networks function in
      concert and that activation in one system influences the other in a reciprocal
      fashion; however, the nature of these influences remains poorly understood. We
      therefore developed a three-component task to assess the interaction effects of
      reward anticipation and conflict resolution on the behavioral performance and the
      activation of brain reward and attentional systems. Sixteen healthy adult
      volunteers aged 21-45 years were scanned with functional magnetic resonance
      imaging (fMRI) while performing the task. A two-way repeated measures analysis of
      variance (ANOVA) with cue (reward vs. non-reward) and target (congruent vs.
      incongruent) as within-subjects factors was used to test for main and interaction
      effects. Neural responses to anticipation, conflict, and reward outcomes were
      tested. Behaviorally there were main effects of both reward cue and target
      congruency on reaction time. Neuroimaging results showed that reward anticipation
      and expected reward outcomes activated components of the attentional networks,
      including the inferior parietal and occipital cortices, whereas surprising non
      rewards activated the frontoinsular cortex bilaterally and deactivated the
      ventral striatum. In turn, conflict activated a broad network associated with
      cognitive control and motor functions. Interaction effects showed decreased
      activity in the thalamus, anterior cingulated gyrus, and middle frontal gyrus
      bilaterally when difficult conflict trials (e.g., incongruent targets) were
      preceded by reward cues; in contrast, the ventral striatum and orbitofrontal
      cortex showed greater activation during congruent targets preceded by reward
      cues. These results suggest that reward anticipation is associated with lower
      activation in attentional networks, possibly due to increased processing
      efficiency, whereas more difficult, conflict trials are associated with lower
      activity in regions of the reward system, possibly because such trials are
      experienced as less rewarding.

PMID- 23170238
TI  - Age- and disease-related features of task-related brain oscillations by using
      mutual information.
AB  - The aim of this study was to investigate changes in task-related brain
      oscillations and corticocortical connections in patients with mild cognitive
      impairment (MCI) and those with normal aging using cross-mutual information (CMI)
      analysis. We hypothesized that task-related brain oscillations and
      corticocortical connections were affected by age- and disease-related changes,
      which could be reflected in the CMI analysis. Electroencephalogram (EEG)
      recordings were measured in 16 MCI patients, 15 healthy age-matched controls, and
      16 healthy younger individuals. The frequencies and interhemispheric CMI data
      were estimated in all groups. The specific EEG rhythms measured were delta
      (delta), theta (theta), alpha (alpha), beta (beta), and gamma (gamma) bands.
      Significant differences in delta, theta, alpha, and beta bands were observed
      between the younger and elderly groups. However, only the theta band was
      significantly different between the elderly and MCI groups. Moreover, this study
      used EEG recordings to investigate age- and disease-related changes in the
      corticocortical connections of the brain. This study proves that the theta-band
      frequency of the connection between the parietal and occipital lobes for the age-
      and disease-related changes can be depicted using the CMI analysis.

PMID- 23170239
TI  - Two critical periods in early visual cortex during figure-ground segregation.
AB  - The ability to distinguish a figure from its background is crucial for visual
      perception. To date, it remains unresolved where and how in the visual system
      different stages of figure-ground segregation emerge. Neural correlates of figure
      border detection have consistently been found in early visual cortex (V1/V2).
      However, areas V1/V2 have also been frequently associated with later stages of
      figure-ground segregation (such as border ownership or surface segregation). To
      causally link activity in early visual cortex to different stages of figure
      ground segregation, we briefly disrupted activity in areas V1/V2 at various
      moments in time using transcranial magnetic stimulation (TMS). Prior to
      stimulation we presented stimuli that made it possible to differentiate between
      figure border detection and surface segregation. We concurrently recorded
      electroencephalographic (EEG) signals to examine how neural correlates of figure
      ground segregation were affected by TMS. Results show that disruption of V1/V2 in
      an early time window (96-119 msec) affected detection of figure stimuli and
      affected neural correlates of figure border detection, border ownership, and
      surface segregation. TMS applied in a relatively late time window (236-259 msec)
      selectively deteriorated performance associated with surface segregation. We
      conclude that areas V1/V2 are not only essential in an early stage of figure
      ground segregation when figure borders are detected, but subsequently causally
      contribute to more sophisticated stages of figure-ground segregation such as
      surface segregation.

PMID- 23170240
TI  - The functional epistasis of 5-HTTLPR and BDNF Val66Met on emotion processing: a
      preliminary study.
AB  - An epistatic interaction of 5-HTTLPR and BDNF Val66Met polymorphisms has been
      implicated in the structure of rostral anterior cingulate cortex (rACC) and
      amygdala (AMY): key regions associated with emotion processing. However, a
      functional epistasis of 5-HTTLPR and BDNF Val66Met on overt emotion processing
      has yet to be determined. Twenty-eight healthy, Caucasian female participants
      provided saliva samples for genotyping and underwent functional magnetic
      resonance imaging (fMRI) during which an emotion processing protocol were
      presented. Confirming the validity of this protocol, we observed blood oxygen
      level-dependent (BOLD) activity consistent with fMRI meta-analyses on emotion
      processing. Region-of-interest analysis of the rACC and AMY revealed main effects
      of 5-HTTLPR and BDNF Val66Met, and an interaction of 5-HTTLPR and BDNF Val66Met.
      The effect of the BDNF Met66 allele was dependent on 5-HTTLPR alleles, such that
      participants with S and Met alleles had the greatest rACC and AMY activation
      during the presentation of emotional images relative to other genetic groupings.
      Increased activity in these regions was interpreted as increased reactivity to
      emotional stimuli, suggesting that those with S and Met alleles are more reactive
      to emotional stimuli relative to other groups. Although limited by a small
      sample, this study contributes novel and preliminary findings relating to a
      functional epistasis of the 5-HTTLPR and BDNF Val66Met genes in emotion
      processing and provides guidance on appropriate methods to determine genetic
      epistasis in fMRI.

PMID- 23170241
TI  - The effects of linguistic relationships among paired associates on verbal self
      generation and recognition memory.
AB  - Previous studies have shown that self-generated information is better remembered
      than information that has been read passively. To further examine this subsequent
      memory effect, we investigated the effect of five different linguistic
      relationships on memory encoding. Ninety subjects were administered 60 paired
      associates during an encoding condition: 30 of the second words from each pair
      were to be read aloud and 30 were to be self-generated from clues as to the
      correct word. Word pairs were composed of five linguistic relationships:
      category, rhyme, opposite, synonym, and association. Subsequently, subjects were
      presented with the words that were read or generated in a forced recognition
      memory task. Overall, reading accuracy was higher than generation accuracy during
      the encoding phase (all P < 0.001). During the recognition phase, subjects'
      performance was better on the generate than on the read conditions for opposite,
      synonym, category, and association relationships (all P < 0.05), with no
      difference in the rhyme relationship. These results confirm previous findings
      that self-generated information is better remembered than read information and
      suggest that this advantage may be mediated by using opposite, synonym, category,
      and association relationships, while rhyme relationship may not extend such an
      advantage. These findings may have implications for future studies of memory
      interventions in healthy controls and subjects with cognitive impairments.

PMID- 23170242
TI  - Theta event-related synchronization is a biomarker for a morbid effect of
      alcoholism on the brain that may partially resolve with extended abstinence.
AB  - Analyzing the induced (non-stimulus-phase-locked) EEG activity elicited by
      targets in a three-condition visual oddball task, Fein and colleagues have shown
      increased theta band event-related synchronization (ERS) in two different samples
      of long-term abstinent alcoholics (LTAA) compared with age- and gender-comparable
      controls. The theta ERS effect in alcoholics was also shown to be independent of,
      and opposite in direction to, the reduced amplitude evoked (stimulus-phase
      locked) activity typically found in alcoholics and those at genetic risk of
      developing alcoholism. This study extends these findings by applying time
      frequency analysis to target stimulus event-related EEG to compare evoked and
      induced theta activity in 43 LTAA and 72 nonalcoholic controls with a group of 31
      alcoholics who just recently initiated abstinence from alcohol (between 6- and 15
      week abstinent; referred to as short-term abstinent alcoholics, STAA). Results
      demonstrated that (1) evoked theta power was reduced to the same degree in STAA
      and LTAA compared with nonalcoholic control participants, while (2) induced theta
      activity, measured by theta ERS, was increased in both STAA and LTAA relative to
      controls, but was also increased in STAA relative to LTAA. The STAA and LTAA
      groups did not differ on measures of alcohol use severity or family history of
      alcohol problems. These results, coupled with previous findings that show a
      relationship between stronger theta ERS and increased memory load and attention
      allocation, suggest that increased theta ERS may be a biomarker for a detrimental
      effect of chronic alcohol abuse on the brain - a detriment that may recover, at
      least partially, with extended abstinence.

PMID- 23170243
TI  - The effects of MAOA genotype, childhood trauma, and sex on trait and state
      dependent aggression.
AB  - Monoamine oxidase A (MAOA) genotypic variation has been associated with variation
      in aggression, especially in interaction with childhood trauma or other early
      adverse events. Male carriers of the low-expressing variant (MAOA-L) with
      childhood trauma or other early adverse events seem to be more aggressive,
      whereas female carriers with the high-expressing variant (MAOA-H) with childhood
      trauma or other early adverse events may be more aggressive. We further
      investigated the effects of MAOA genotype and its interaction with sex and
      childhood trauma or other early adverse events on aggression in a young adult
      sample. We hypothesized that the association between genotype, childhood trauma,
      and aggression would be different for men and women. We also explored whether
      this association is different for dispositional (trait) aggression versus
      aggression in the context of dysphoric mood. In all, 432 Western European
      students (332 women, 100 men; mean age 20.2) were genotyped for the MAOA gene.
      They completed measures of childhood trauma, state and trait measures of
      aggression-related behaviors (STAXI), and cognitive reactivity to sad mood (LEIDS
      R), including aggression reactivity. Women with the MAOA-H had higher aggression
      reactivity scores than women with the MAOA-L. This effect was not observed in
      men, although the nonsignificant findings in men may be a result of low power.
      Effects on the STAXI were not observed, nor were there gene by environment
      interactions on any of the aggression measures. A protective effect of the low
      expression variant in women on aggression reactivity is consistent with previous
      observations in adolescent girls. In females, the MAOA-H may predispose to
      aggression-related problems during sad mood.

PMID- 23170244
TI  - Open label, randomized, crossover pilot trial of high-resolution, relational,
      resonance-based, electroencephalic mirroring to relieve insomnia.
AB  - Effective noninvasive interventions for insomnia are needed. High-resolution,
      relational, resonance-based, electroencephalic mirroring (HIRREMTM) is a
      noninvasive, electroencephalography (EEG)-based method to facilitate greater
      client-unique, autocalibrated improvements of balance and harmony in cortical
      neural oscillations. This study explores using HIRREM for insomnia. Twenty
      subjects, with an Insomnia Severity Index (ISI) score of >=15 (14 women, mean age
      45.4, mean ISI 18.6), were enrolled in this randomized, unblinded, wait-list
      control, crossover, superiority study. Subjects were randomized to receive 8-12
      HIRREM sessions over 3 weeks, plus usual care (HUC), or usual care alone (UC).
      Pre- and post-HIRREM data collection included ISI (primary outcome), and many
      secondary, exploratory measures (CES-D, SF-36, HR, BP, neurocognitive testing,
      and VAS scales). The UC group later crossed over to receive HIRREM. ISI was also
      repeated 4-6 weeks post-HIRREM. All subjects completed the primary intervention
      period. Analysis for differential change of ISI in the initial intervention
      period for HUC versus UC showed a drop of 10.3 points (95% CI: -13.7 to -6.9, P <
      0.0001, standardized effect size of 2.68). Key secondary outcomes included
      statistically identical differential change for the crossed-over UC group, and
      persistence of the effect on the ISI up to > 4 weeks post-HIRREM. Differential
      change in the HUC group was also statistically significant for CES-D (-8.8, 95%
      CI: -17.5 to -0.1, P = 0.047), but other exploratory outcomes were not
      statistically significant. For all receiving HIRREM (n = 19), decreased high
      frequency total power was seen in the bilateral temporal lobes. No adverse events
      were seen. This pilot clinical trial, the first using HIRREM as an intervention,
      suggests that HIRREM is feasible and effective for individuals having moderate-to
      severe insomnia, with clinically relevant, statistically significant benefits
      based on differential change in the ISI. Effects persisted for 4 weeks after
      completion of HIRREM. Larger controlled clinical trials are warranted.

PMID- 23170245
TI  - Functional near-infrared spectroscopy for the assessment of overt reading.
AB  - Functional near-infrared spectroscopy (fNIRS) has become increasingly established
      as a promising technique for monitoring functional brain activity. To our
      knowledge, no study has yet used fNIRS to investigate overt reading of irregular
      words and nonwords with a full coverage of the cerebral regions involved in
      reading processes. The aim of our study was to design and validate a protocol
      using fNIRS for the assessment of overt reading. Twelve healthy French-speaking
      adults underwent one session of fNIRS recording while performing an overt reading
      of 13 blocks of irregular words and nonwords. Reading blocks were separated by
      baseline periods during which participants were instructed to fixate a cross.
      Sources (n = 55) and detectors (n = 16) were placed bilaterally over frontal,
      temporal, parietal, and occipital regions. Two wavelengths were used: 690 nm,
      more sensitive to deoxyhemoglobin (HbR) concentration changes, and 830 nm, more
      sensitive to oxyhemoglobin (HbO) concentration changes. For all participants,
      total hemoglobin (HbT) concentrations (HbO + HbR) were significantly higher than
      baseline for both irregular word and nonword reading in the inferior frontal
      gyri, the middle and superior temporal gyri, and the occipital cortices
      bilaterally. In the temporal gyri, although the difference was not significant,
      [HbT] values were higher in the left hemisphere. In the bilateral inferior
      frontal gyri, higher [HbT] values were found in nonword than in irregular word
      reading. This activation could be related to the grapheme-to-phoneme conversion
      characterizing the phonological pathway of reading. Our findings confirm that
      fNIRS is an appropriate technique to assess the neural correlates of overt
      reading.

PMID- 23170246
TI  - Isolated CNS Whipple disease with normal brain MRI and false-positive CSF 14-3-3
      protein: a case report and review of the literature.
AB  - Whipple disease (WD) is usually a systemic infectious disease that can have
      central nervous system (CNS) involvement. WD confined to the CNS is extremely
      rare and difficult to diagnose, but can be fatal if not treated in a timely
      fashion. We present the case of a 42-year-old man with a subacute dementia
      accompanied by a movement disorder consisting of progressive supranuclear gaze
      palsy, myoclonus, and ataxia. Our patient lacked the typical magnetic resonance
      imaging (MRI) findings reported with isolated CNS WD and had a false-positive
      cerebrospinal fluid (CSF) 14-3-3 protein. The patient expired, and definitive
      diagnosis of isolated CNS WD was made by autopsy with characteristic macrophage
      accumulations found in the brain but not in the gastrointestinal tract. We
      examine the literature on isolated CNS WD and discuss how these previously
      unreported findings make a rare diagnosis even more challenging. The reported
      patient is the first in the literature with tissue diagnosis of isolated CNS WD
      in the setting of normal brain MRI and positive CSF 14-3-3 protein. Isolated CNS
      WD should be added to the list of considerations for a false-positive CSF 14-3-3
      protein. Even in the absence of typical MRI lesions, a patient with subacute
      progressive dementia, supranuclear gaze palsy, and other various neurologic
      abnormalities should have the diagnosis of isolated CNS WD considered.

PMID- 23170248
TI  - T-cell dependent immunoselection.

PMID- 23170249
TI  - Immunotherapy with HER-2 and VEGF peptide mimics plus metronomic paclitaxel
      causes superior antineoplastic effects in transplantable and transgenic mouse
      models of human breast cancer.
AB  - HER-2 and the vascular endothelial factor receptor (VEGF) represent validated
      targets for the therapy of multiple tumor types and inhibitors of these receptors
      have gained increasing importance in the clinic. In this context, novel bioactive
      agents associated with better therapeutic outcomes and improved safety profile
      are urgently required. Specifically engineered HER-2- and VEGF-derived peptides
      in combination with low-dose chemotherapy might provide a substantial impact on
      tumor metastasis and cancer progression. We tested the antitumor effects of HER-2
      and VEGF peptide mimics in combination with metronomic paclitaxel in both PyMT
      and Balb/c murine model challenged with TUBO cells. The combination of low-dose
      paclitaxel and HER-2 or VEGF peptide mimics had greater inhibitory effects than
      either agent alone. Peptide treatment caused virtually no cardiotoxic effects,
      while paclitaxel and the anti-HER-2 antibody trastuzumab (Herceptin), exerted
      consistent cardiotoxicity. The combination regimen also promoted significant
      reductions in tumor burden and prolonged survival rates in both transgenic and
      transplantable tumor models. Tumor weights were significantly reduced in mice
      treated with HER-2 peptides alone, and even more in animals that received HER-2
      peptide with low-dose paclitaxel, which alone had no significant effects on tumor
      growth in the transgenic model. Specifically engineered native peptide sequences
      from HER-2 and VEGF used in combination with metronomic paclitaxel demonstrate
      enhanced anticancer efficacy and an encouraging safety profile. This novel
      approach to targeted therapy may offer new avenues for the treatment of breast
      cancer and other solid tumors that overexpress HER-2 and VEGF.

PMID- 23170250
TI  - Primary sterile necrotic cells fail to cross-prime CD8(+) T cells.
AB  - Necrotic cells are known to activate the innate immune system and trigger
      inflammation by releasing damage associated molecular patterns (DAMPs). However,
      how necrotic cells influence the induction of antigen-specific CD8(+) T cell
      mediated adaptive immune responses under sterile conditions, in the absence of
      pathogen associated molecular patterns (PAMPs), remains poorly understood. Here,
      we examined antigen-specific CD8(+) T-cell responses to primary sterile necrotic
      tumor cells both in vitro and in vivo. We found that primary necrotic cells alone
      fail to generate CD8(+) T cell-dependent immune responses toward cell-associated
      antigens. We show that necrotic cells trigger CD8(+) T-cell immunity only in the
      presence of PAMPs or analogs, such as p(dI-dC) and/or unmethylated CpG DNA. The
      electroporation of tumor cells with these PAMPs prior to necrosis induction
      triggered antigen-specific CD8(+) T-cell responses through a TLR9/MyD88-dependent
      pathway. In addition, we found that necrotic cells contain factors that can block
      the cross-priming of CD8(+) T cells even under non-sterile conditions and can
      serve as a possible mechanism of immunosuppression. These results suggest that
      antigen-specific CD8(+) T-cell responses to primary necrotic tumor cells can be
      induced in the presence of PAMPs and thus have a substantial impact on the
      development of antitumor vaccination strategies.

PMID- 23170251
TI  - Conditional IFNAR1 ablation reveals distinct requirements of Type I IFN signaling
      for NK cell maturation and tumor surveillance.
AB  - Mice with an impaired Type I interferon (IFN) signaling (IFNAR1- and IFNbeta
      deficient mice) display an increased susceptibility toward v-ABL-induced B-cell
      leukemia/lymphoma. The enhanced leukemogenesis in the absence of an intact Type I
      IFN signaling is caused by alterations within the tumor environment. Deletion of
      Ifnar1 in tumor cells (as obtained in Ifnar1(f/f) CD19-Cre mice) failed to impact
      on disease latency or type. In line with this observation, the initial
      transformation and proliferative capacity of tumor cells were unaltered
      irrespective of whether the cells expressed IFNAR1 or not. v-ABL-induced
      leukemogenesis is mainly subjected to natural killer (NK) cell-mediated tumor
      surveillance. Thus, we concentrated on NK cell functions in IFNAR1 deficient
      animals. Ifnar1(-/-) NK cells displayed maturation defects as well as an impaired
      cytolytic activity. When we deleted Ifnar1 selectively in mature NK cells (by
      crossing Ncr1-iCre mice to Ifnar1(f/f) animals), maturation was not altered.
      However, NK cells derived from Ifnar1(f/f) Ncr1-iCre mice showed a significant
      cytolytic defect in vitro against the hematopoietic cell lines YAC-1 and RMA-S,
      but not against the melanoma cell line B16F10. Interestingly, this defect was not
      related to an in vivo phenotype as v-ABL-induced leukemogenesis was unaltered in
      Ifnar1(f/f )Ncr1-iCre compared with Ifnar1(f/f) control mice. Moreover, the
      ability of Ifnar1(f/f) Ncr1-iCre NK cells to kill B16F10 melanoma cells was
      unaltered, both in vitro and in vivo. Our data reveal that despite the necessity
      for Type I IFN in NK cell maturation the expression of IFNAR1 on mature murine NK
      cells is not required for efficient tumor surveillance.

PMID- 23170252
TI  - Single low-dose cyclophosphamide combined with interleukin-12 gene therapy is
      superior to a metronomic schedule in inducing immunity against colorectal
      carcinoma in mice.
AB  - The use of conventional cytotoxic agents at metronomic schedules, alone or in
      combination with targeted agents or immunotherapy, is being explored as a
      promising anticancer strategy. We previously reported a potent antitumor effect
      of a single low-dose cyclophosphamide and interleukin-12 (IL-12) gene therapy
      against advanced gastrointestinal carcinoma, in mice. Here, we assessed whether
      the delivery of IL-12 by gene therapy together with metronomic cyclophosphamide
      exerts antitumor effects in a murine model of colorectal carcinoma. This
      combination therapy was able, at least in part, to reverse immunosuppression, by
      decreasing the number of regulatory T cells (Tregs) as well as of splenic myeloid
      derived suppressor cells (MDSCs). However, metronomic cyclophosphamide plus IL-12
      gene therapy failed to increase the number of tumor-infiltrating T lymphocytes
      and, more importantly, to induce a specific antitumor immune response. With
      respect to this, cyclophosphamide at a single low dose displayed a superior
      anticancer profile than the same drug given at a metronomic schedule. Our results
      may have important implications in the design of new therapeutic strategies
      against colorectal carcinoma using cyclophosphamide in combination with
      immunotherapy.

PMID- 23170253
TI  - Combined vaccination with HER-2 peptide followed by therapy with VEGF peptide
      mimics exerts effective anti-tumor and anti-angiogenic effects in vitro and in
      vivo.
AB  - Overexpression of HER-2 and VEGF plays a key role in the development and
      metastasis of several human cancers. Many FDA-approved therapies targeting both
      HER-2 (Trastuzumab, Herceptin) and VEGF (Bevacizumab, Avastin) are expensive,
      have unacceptable toxicities and are often associated with the development of
      resistance. Here, we evaluate the dual antitumor effects of combining designed
      particular HER-2 peptide vaccine with VEGF peptide mimics. In vitro, HER-2
      phosphorylation and antibody-dependent cellular toxicity were used to validate
      whether combining HER-2- and VEGF-targeting therapies would be effective.
      Moreover, a two-pronged approach was tested in vivo: (1) active immunotherapy
      with conformational HER-2 B-cell epitope vaccines and (2) anti-angiogenic therapy
      with a peptide structured to mimic VEGF. A transplantable BALB/c mouse model
      challenged with TUBO cells was used to test the effects of the HER-2 peptide
      vaccine combined with VEGF peptide mimics. Tumor sections after treatment were
      stained for blood vessel density and actively dividing cells. Our results show
      that immunization with an HER-2 peptide epitope elicits high affinity HER-2
      native antibodies that are effective in inhibiting tumor growth in vivo, an
      effect that is enhanced by VEGF peptide mimics. We demonstrate that the
      combination of HER-2 and VEGF peptides induces potent anti-tumor and anti
      angiogenic responses.

PMID- 23170254
TI  - B7-H1 limits the entry of effector CD8(+) T cells to the memory pool by
      upregulating Bim.
AB  - Protective T-cell immunity against cancer and infections is dependent on the
      generation of a durable effector and memory T-cell pool. Studies from cancer and
      chronic infections reveal that B7-H1 (PD-L1) engagement with its receptor PD-1
      promotes apoptosis of effector T cells. It is not clear how B7-H1 regulates T
      cell apoptosis and the subsequent impact of B7-H1 on the generation of memory T
      cells. In immunized B7-H1-deficient mice, we detected an increased expansion of
      effector CD8(+) T cells and a delayed T-cell contraction followed by the
      emergence of a protective CD8(+) T-cell memory capable of completely rejecting
      tumor metastases in the lung. Intracellular staining revealed that antigen-primed
      CD8(+) T cells in B7-H1-deficient mice express lower levels of the pro-apoptotic
      molecule Bim. The engagement of activated CD8(+) T cells by a plate-bound B7-H1
      fusion protein led to the upregulation of Bim and increased cell death. Assays
      based on blocking antibodies determined that both PD-1 and CD80 are involved in
      the B7-H1-mediated regulation of Bim in activated CD8(+) T cells. Our results
      suggest that B7-H1 may negatively regulate CD8(+) T-cell memory by enhancing the
      depletion of effector CD8(+) T cells through the upregulation of Bim. Our
      findings may provide a new strategy for targeting B7-H1 signaling in effector
      CD8(+) T cells to achieve protective antitumor memory responses.

PMID- 23170255
TI  - Dendritic cell exosomes directly kill tumor cells and activate natural killer
      cells via TNF superfamily ligands.
AB  - Autocrine and paracrine cell communication can be conveyed by multiple mediators,
      including membrane-associate proteins, secreted proteins and exosomes. Exosomes
      are 30-100 nm endosome-derived vesicles consisting in cytosolic material
      surrounded by a lipid bilayer containing transmembrane proteins. We have
      previously shown that dendritic cells (DCs) express on their surface multiple TNF
      superfamily ligands (TNFSFLs), by which they can induce the apoptotic demise of
      tumor cells as well as the activation of natural killer (NK) cells. In the
      present study, we demonstrate that, similar to DCs, DC-derived exosomes (DCex)
      express on their surface TNF, FasL and TRAIL, by which they can trigger caspase
      activation and apoptosis in tumor cells. We also show that DCex activate NK cells
      and stimulate them to secrete interferongamma (IFNgamma) upon the interaction of
      DCex TNF with NK-cell TNF receptors. These data demonstrate that DCex can mediate
      essential innate immune functions that were previously ascribed to DCs.

PMID- 23170256
TI  - Loss of antigen cross-presentation after complete tumor resection is associated
      with the generation of protective tumor-specific CD8(+) T-cell immunity.
AB  - An incomplete understanding on the effect of surgery on tumor-specific immunity
      continues to hamper efforts to combine surgery with immunotherapy in the clinic.
      Herein, we describe the impact of tumor resection on the tumor-specific T-cell
      response, showing that complete tumor resection is associated with (1) a decline
      in the amount of cross-presented tumor antigens, (2) a decline of cytolytic tumor
      specific CD8(+) T cell activity, and (3) the development of systemic CD8(+) T
      cell-mediated protective immunity. Our findings are consistent with a model
      whereby tumor resection releases antitumor CD8(+) T cells from chronic antigen
      exposure, allowing a gradual differentiation toward functional antitumor memory T
      cells. This process depends on sentinel lymph nodes, as their removal at the time
      of surgery was associated with a strong negative effect on survival. We conclude
      that complete tumor resection provides a unique environment that boosts
      protective immunological memory and might provide a powerful platform for
      immunotherapy. Our findings also carry important implications for the design and
      timing of post-surgery immunotherapeutic regimens.

PMID- 23170257
TI  - Detecting T-cell reactivity to whole cell vaccines: Proof of concept analysis of
      T-cell response to K562 cell antigens in CML patients.
AB  - BCR-ABL(+) K562 cells hold clinical promise as a component of cancer vaccines,
      either as bystander cells genetically modified to express immunostimulatory
      molecules, or as a source of leukemia antigens. To develop a method for detecting
      T-cell reactivity against K562 cell-derived antigens in patients, we exploited
      the dendritic cell (DC)-mediated cross-presentation of proteins generated from
      apoptotic cells. We used UVB irradiation to consistently induce apoptosis of K562
      cells, which were then fed to autologous DCs. These DCs were used to both
      stimulate and detect antigen-specific CD8(+) T-cell reactivity. As proof-of
      concept, we used cross-presented apoptotic influenza matrix protein-expressing
      K562 cells to elicit reactivity from matrix protein-reactive T cells. Likewise,
      we used this assay to detect increased anti-CML antigen T-cell reactivity in CML
      patients that attained long-lasting clinical remissions following immunotherapy
      (donor lymphocyte infusion), as well as in 2 of 3 CML patients vaccinated with
      lethally irradiated K562 cells that were modified to secrete high levels of
      granulocyte macrophage colony-stimulating factor (GM-CSF). This methodology can
      be readily adapted to examine the effects of other whole tumor cell-based
      vaccines, a scenario in which the precise tumor antigens that stimulate immune
      responses are unknown.

PMID- 23170258
TI  - Expression of MHC Class I on breast cancer cells correlates inversely with HER2
      expression.
AB  - HER2 is a promising target for immunotherapeutic interventions with T cell-based
      approaches since it is amplified and overexpressed in 20-30% of breast cancers.
      However, several previous studies including ours showed that HER2-overexpressing
      tumors may escape cytotoxic T lymphocyte-mediated lysis by downregulating MHC
      Class I and components of the antigen-processing machinery. The aims of the
      present study were to analyze the relationship between HER2 and MHC Class I
      expression and to elucidate the mechanisms underlying MHC Class I downregulation
      in breast cancer. We explored expression of HER2, MHC Class I, PTEN, Ki67,
      estrogen and progesterone expression in 70 breast cancer patients by
      immunohistochemistry (IHC) and analyzed their correlation. We also explored the
      components of the signal transduction pathway that are involved in the regulation
      of MHC Class I expression using small-interfering RNAs targeting HER2 as well as
      an inhibitor of HER2 signaling. HER2 expression in breast cancers correlated
      inversely with MHC Class I expression analyzed by IHC. HER2 depletion by small
      interfering RNAs resulted in MHC Class I upregulation. Moreover, MHC Class I
      expression on breast cancer cell lines was upregulated by PD98059, an inhibitor
      of mitogen-associated protein kinases, in a dose-dependent manner. Thus, agents
      that target the MAPK signaling pathway may increase MHC Class I expression in
      breast cancer cells.

PMID- 23170260
TI  - Instruction of myeloid cells by the tumor microenvironment: Open questions on the
      dynamics and plasticity of different tumor-associated myeloid cell populations.
AB  - The versatility and plasticity of myeloid cell polarization/differentiation has
      turned out to be crucial in health and disease, and has become the subject of
      intense investigation during the last years. On one hand, myeloid cells provide a
      critical contribution to tissue homeostasis and repair. On the other hand,
      myeloid cells not only play an important role as first line defense against
      pathogens but also they are involved in a broad array of inflammation-related
      diseases such as cancer. Recent studies show that macrophages can exist in
      different activation states within the same tumor, underlining their plasticity
      and heterogeneity. In this review, we will discuss recent evidence on how the
      tumor microenvironment, as it evolves, shapes the recruitment, function,
      polarization and differentiation of the myeloid cell compartment, leading to the
      selection of myeloid cells with immunosuppressive and angiogenic functions that
      facilitate tumor progression and dissemination.

PMID- 23170262
TI  - Immunoglobulin kappa chain as an immunologic biomarker of prognosis and
      chemotherapy response in solid tumors.
AB  - Infiltration of plasma cells is associated with better prognosis in breast, lung
      and colon cancer. Immunoglobulin kappa chain (IGKC) is now available as a single,
      robust immune marker predicting metastasis-free survival and response to
      chemotherapy. This will facilitate a deeper understanding of the role of the
      humoral immune system in cancer development.

PMID- 23170263
TI  - Friend or foe:  A novel role of beta-defensins in tumor development.
AB  - For many years, beta-defensins were best known for their antimicrobial activity.
      However, beta-defensins also exert immunomodulatory functions, such as the
      chemotactic recruitment of immune cells via chemokine receptors. We demonstrated
      that mouse beta-defensin 14 recruits CCR6(+) B cells into fibrosarcomas,
      resulting in enhanced angiogenesis and tumor development.

PMID- 23170261
TI  - A model for cancer-suppressive inflammation.
AB  - In oncology, inflammation is generally regarded as a cancer-promoting process
      only. Here, we argue that this view may represent a misleading
      oversimplification. We present evidence from our own work and from the literature
      documenting cancer-suppressive aspects of inflammation. We propose that specific
      types of inflammation, in particular inflammation driven by tumor-specific Th1
      cells, may repress rather than promote cancer. Th1 cells collaborate with tumor
      infiltrating M1 macrophages to efficiently recognize and eliminate malignant
      cells. In a Th1 environment, pro-inflammatory cytokines such as interleukin (IL)
      1alpha, IL-1beta, IL-6 and tumor-necrosis factor alpha (TNFalpha) enhance anti
      cancer immunity. Inducing Th1-type inflammation may significantly improve
      immunotherapeutic strategies against cancer.

PMID- 23170264
TI  - Redirecting neutrophils against bladder cancer cells by BCG and Smac mimetic
      combination.
AB  - Intravesical bacillus Calmette-Guerin (BCG) immunotherapy results in neutrophil
      recruitment and subsequent secretion of cytokines to eliminate non-muscle
      invasive bladder cancer cells. However, bladder cancer cells often resist BCG
      immunotherapy. Thus, understanding the mechanism of action of BCG, and designing
      appropriate combination therapies might help to overcome BCG resistance and
      redirect neutrophils against bladder cancer cells.

PMID- 23170265
TI  - Hunting for clues: Regulatory T cells and colorectal cancer.
AB  - Colorectal cancer is a common disease which appears to be influenced by anti
      tumor immune responses. Here we discuss our recent study(1) which tracked anti
      tumor CD4(+) T cell responses before and after surgical resection, highlighting
      the importance of regulatory T cells (T(regs)) in controlling these responses,
      and the influence of the tumor on these specific T-cell populations.

PMID- 23170266
TI  - Rage mediated DAMP signaling in intestinal tumorigenesis.
AB  - In the intestine, a large variety of pathogen-associated molecular patterns
      (PAMPs) and damage-associated molecular patterns (DAMPs) can instigate innate
      immune responses, which have been shown to promote colorectal carcinogenesis. We
      have recently demonstrated an important role for the receptor for advanced
      glycation end products (Rage) in intestinal adenoma formation. Rage is a receptor
      for DAMPs that are present in several proteins produced in intestinal adenomas.
      We found that Rage signaling upholds a pro-inflammatory milieu through a feed
      forward loop that stimulates the production of its own ligands.

PMID- 23170267
TI  - Combination of vaccine and immune checkpoint inhibitor is safe with encouraging
      clinical activity.
AB  - This commentary provides the authors' perspective on the article "Ipilimumab and
      a poxviral vaccine targeting prostate-specific antigen in metastatic castration
      resistant prostate cancer: a phase 1 dose-escalation trial," which has recently
      been published in The Lancet Oncology.

PMID- 23170268
TI  - Personalizing immunotherapy: Balancing predictability and precision.
AB  - Despite great expectations and research efforts, anticancer immunotherapy has not
      yet become a definitive cure. Perhaps, this is because past reductionist
      approaches were too simplistic for the patient-specific complex system of co
      evolving tumor cells and host immunity. Recent efforts based on a systems-based
      approach promise improved clinical outcomes engendered by a dynamic modification
      of personalized therapeutic regimens.

PMID- 23170259
TI  - Trial watch:  Dendritic cell-based interventions for cancer therapy.
AB  - Dendritic cells (DCs) occupy a central position in the immune system,
      orchestrating a wide repertoire of responses that span from the development of
      self-tolerance to the elicitation of potent cellular and humoral immunity.
      Accordingly, DCs are involved in the etiology of conditions as diverse as
      infectious diseases, allergic and autoimmune disorders, graft rejection and
      cancer. During the last decade, several methods have been developed to load DCs
      with tumor-associated antigens, ex vivo or in vivo, in the attempt to use them as
      therapeutic anticancer vaccines that would elicit clinically relevant immune
      responses. While this has not always been the case, several clinical studies have
      demonstrated that DC-based anticancer vaccines are capable of activating tumor
      specific immune responses that increase overall survival, at least in a subset of
      patients. In 2010, this branch of clinical research has culminated with the
      approval by FDA of a DC-based therapeutic vaccine (sipuleucel-T, Provenge((r)))
      for use in patients with asymptomatic or minimally symptomatic metastatic hormone
      refractory prostate cancer. Intense research efforts are currently dedicated to
      the identification of the immunological features of patients that best respond to
      DC-based anticancer vaccines. This knowledge may indeed lead to personalized
      combination strategies that would extend the benefit of DC-based immunotherapy to
      a larger patient population. In addition, widespread enthusiasm has been
      generated by the results of the first clinical trials based on in vivo DC
      targeting, an approach that holds great promises for the future of DC-based
      immunotherapy. In this Trial Watch, we will summarize the results of recently
      completed clinical trials and discuss the progress of ongoing studies that have
      evaluated/are evaluating DC-based interventions for cancer therapy.

PMID- 23170269
TI  - Combinatorial Immunotherapy: PD-1 may not be LAG-ing behind any more.
AB  - Cancer immunotherapy attempts to harness the immune system by breaking tolerance
      and generating a robust anticancer response. We have recently demonstrated a
      synergistic enhancement in tumor clearance following therapeutic, dual PD-1 and
      LAG-3 blockade. Here, we discuss the implications of these findings in the
      context of future combinatorial immunotherapeutic approaches.

PMID- 23170270
TI  - RhoGDI2 suppresses bladder cancer metastasis via reduction of inflammation in the
      tumor microenvironment.
AB  - Low expression of RhoGDI2 is associated with poor outcome in cancer patients. In
      animal models, RhoGDI2 suppresses lung metastasis by reducing the expression of
      the proteoglycan versican, whose levels portend poor patient prognosis. Versican
      promotes metastasis through enhanced tumor migration and creation of an
      inflammatory lung environment involving macrophages and the CCL2/CCR2 signaling
      axis. Targeting this mechanism may provide novel adjuvant strategies for delaying
      the appearance of clinical metastasis.

PMID- 23170271
TI  - Activation of systemic antitumor immunity via TRAIL-induced apoptosis.
AB  - TNF-related apoptosis-inducing ligand (TRAIL) continues to be intently studied as
      a cancer therapeutic because of its selective tumoricial activity. We have been
      interesting in evaluating the ability of TRAIL to induce systemic antitumor
      immunity through the generation of apoptotic tumor cells. Recent observations
      suggest that localized administration of TRAIL in combination with CpG ODN
      generates a systemic antitumor immune response to eliminate the primary tumor and
      distant metastases.

PMID- 23170272
TI  - Interleukin-2 treatment of tumor patients can expand regulatory T cells.
AB  - Augmented numbers of regulatory T cells contribute to the overall
      immunosuppression in tumor patients. Interleukin-2 has been widely used in the
      clinics in anticancer therapy, yet evidence has accumulated that the major
      drawback, limiting clinical efficacy, is the expansion of regulatory T cells,
      which aggravates immunosuppression.

PMID- 23170273
TI  - Blocking IL-10 enhances bacillus Calmette-Guerin induced T helper Type 1 immune
      responses and anti-bladder cancer immunity.
AB  - Proper induction of Th1 immunity is required for effective immunotherapy of
      bladder cancer with the bacillus Calmette-Guerin (BCG). Interleukin-10 (IL-10)
      downregulates the Th1 immune response and is associated with BCG therapy failure.
      We evaluated BCG plus IL-10 blocking antibodies and found that this combination
      therapy induces enhanced Th1 immune responses and anti-bladder cancer immunity in
      preclinical animal models.

PMID- 23170274
TI  - Tumor-infiltrating B cells: The ignored players in tumor immunology.
AB  - B cells infiltrating into solid tumors are poorly investigated despite their
      described positive prognostic value. Whether this antitumor potential comes from
      either the antigen presentation or the antibody production capacity of B cells,
      or both, is unknown. Our recently published method on tumor-infiltrating B
      lymphocyte cloning may prove helpful in unraveling the actual relevance of these
      cells for tumor development and response to therapy.

PMID- 23170275
TI  - Rapamycin: A rheostat for CD8(+) T-cell-mediated tumor therapy.
AB  - Vaccines that generate Ag-specific CD8(+) T-cell responses of appropriate
      quality, magnitude and duration are highly desirable. The ability of mTOR to
      regulate CD8(+) T-cell functional differentiation must be exploited for clinical
      benefit. In a recent paper, we report that varying the regimen of rapamycin
      administration regulates viral vaccine-induced CD8(+) T-cell responses for tumor
      immunity. These observations validate the use of rapamycin in vaccination
      strategies and demonstrate the efficacy of memory CD8(+) T-cell responses for
      tumor immunity.

PMID- 23170276
TI  - Targeting the right regulatory T-cell population for tumor immunotherapy.
AB  - Regulatory T cells (Tregs) that suppress tumor-specific T cell-mediated immune
      responses are the subject of an intense wave of investigation. We recently
      reported that a subset of Tregs, namely effector/memory CD25(low) cells, are
      responsible for suppressing high avidity tumor-specific T cells in mouse mammary
      tumors. Here, we discuss additional findings that clarify this mechanism of Treg
      mediated immunosuppression.

PMID- 23170277
TI  - Cancer testis antigens: A new paradigm for cancer therapy.
AB  - Cancer immunotherapy is a promising field with limited success, also due to lack
      of tumor-specific targets. In our attempt of exploring novel biomarkers and
      immunotherapeutic targets against cancer, we have discovered a novel cancer
      testis antigen, SPAG9, in cancers of different histological origin and
      demonstrated its potential role in oncogenesis.

PMID- 23170278
TI  - Ipilimumab in a Phase II trial of melanoma patients with brain metastases.
AB  - In a Phase II clinical study enrolling individuals with melanoma brain
      metastases, 51 asymptomatic patients (cohort A) and 21 on a stable steroid dose
      (cohort B) received 4 courses of 10 mg/kg intravenous ipilimumab (induction),
      then (at 24 weeks) maintenance therapy with the same dose of ipilimumab every 12
      weeks. Disease control rate at 12 weeks was 18% (according to the modified WHO
      criteria) and 26% (according to the immune-related response criteria) in cohort A
      (median survival = 7 mo) and 5% and 10% in cohort B (median survival = 4 mo).
      Toxicities were as previously reported for ipilimumab patients without brain
      metastases.

PMID- 23170279
TI  - Opposing consequences of signaling through EGF family members: Escape from CTLs
      could be a bait for NK cells.
AB  - Oncogenes have been traditionally viewed as molecular drivers for tumor growth
      and survival. Recent evidence indicates that oncogenes may facilitate the escape
      of malignant cells from immune recognition and elimination. In this article, we
      discuss the implications of the overexpression of epidermal growth factor
      receptor (EGFR) family members on immune escape of tumors and immunotherapy.

PMID- 23170280
TI  - Flipping the script on macrophages in leiomyosarcoma.
AB  - Macrophages promote the growth of leiomyosarcoma (LMS), a malignant soft-tissue
      tumor. CD47 on tumor cells binds to the macrophagic receptor signal regulatory
      protein alpha (SIRPalpha) and prevents phagocytosis. We showed that anti-CD47
      monoclonal antibodies (mAbs) allow macrophages to engulf LMS cells and prevent
      tumor growth and metastases. Therefore, anti-CD47 mAbs represent a promising
      targeted immunotherapy for LMS.

PMID- 23170281
TI  - Stromal CEACAM1 expression regulates colorectal cancer metastasis.
AB  - Colorectal cancer metastasis to Ceacam1-/- livers is significantly impaired,
      compared with wild type livers, due to decreased endothelial cell survival,
      reduced tumor cell proliferation, diminished immune infiltration and altered
      chemokine expression. Ceacam1-/- myeloid-derived suppressor cells diminish
      metastatic burden, as confirmed by bone marrow transplantation and adoptive
      transfer experiments.

PMID- 23170282
TI  - Specificity may be overrated in cancer immunotherapy: Getting to know the
      nonspecific side of memory T Cells.
AB  - For a long time, cancer immunotherapy has focused on the induction of tumor
      specific T cell-mediated immune responses. Now, a mounting body of evidence
      indicates that efficient anticancer immune responses also rely on innate
      immunity. Tietze et al. have recently elucidated an antigen-nonspecific role for
      memory CD8(+) T cells in cytokine-based cancer immunotherapy.

PMID- 23170283
TI  - CD4 responses against IDO.
AB  - Natural indoleamine-2,3-dioxygenase (IDO)-reactive CD4(+) T cells have been shown
      to release interferongamma (IFNgamma), tumor necrosis factor alpha (TNFalpha), as
      well as interleukin 17 (IL-17). In some individuals, these cells also
      demonstrated the ability to suppress IL-10 production. IDO-specific CD4(+) helper
      T cells among peripheral blood lymphocytes may participate in immunoregulatory
      networks by delaying the immune suppressive actions of IDO. However, IDO-specific
      CD4(+) T cells may also have a regulatory phenotype, de facto exerting
      immunosuppressive functions.

PMID- 23170284
TI  - Targeted cancer immunotherapy: Mimicking physiological trans-presentation of IL
      15.
AB  - Under physiological conditions, the trans-presentation of interleukin-15 (IL-15)
      by the IL-15 receptor alpha on the cell surface allows to confine and tune the IL
      15-mediated immune responses. Therefore, targeting strategies that mimic this
      situation at the tumor sites appear especially promising for anticancer
      immunotherapy.

PMID- 23170285
TI  - Production of epitope-specific antibodies using peptide-CpG-ODN-liposome complex
      without carriers and their application as a cancer vaccine in mice.
AB  - Low efficacy of peptide vaccines limits their potential application. We developed
      a powerful strategy to produce epitope-specific antibodies using peptides.
      Immunization with novel formula into mice showed target-specific prophylactic and
      therapeutic effects against tumors. Our strategy will be useful for rapid eiptope
      screening, therapeutic antibody production and cancer vaccine development.

PMID- 23170286
TI  - Activation of dendritic cells by tumor cell death.
AB  - A growing number of studies indicate that cell death can be either immunogenic or
      not, depending on its modalities, the type and the activation state of the cells,
      and finally, the environment where it happens. Increased understanding of the
      immunogenicity of cancer cell death will significantly improve the outcome of
      chemotherapeutic treatments.

PMID- 23170287
TI  - Opposing effects of androgen ablation on immune function in prostate cancer.
AB  - Although it is recognized that immune function is modulated by androgen ablation
      therapy for prostate cancer, the long-term consequences are not completely
      understood. We recently showed that both effector and inhibitory immune
      mechanisms are amplified by androgen ablation, providing one explanation for only
      transient increases in immune function after castration.

PMID- 23170288
TI  - Clinical predictive factors of pathologic tumor response after preoperative
      chemoradiotherapy in rectal cancer.
AB  - PURPOSE: The aim of this study was to identify clinical predictive factors for
      tumor response after preoperative chemoradiotherapy (CRT) in rectal cancer.
      MATERIALS AND METHODS: The study involved 51 patients who underwent preoperative
      CRT followed by surgery between January 2005 and February 2012. Radiotherapy was
      delivered to the whole pelvis at a dose of 45 Gy in 25 fractions, followed by a
      boost of 5.4 Gy in 3 fractions to the primary tumor with 5 fractions per week.
      Three different chemotherapy regimens were used (5-fluorouracil and leucovorin,
      capecitabine, or tegafur/uracil). Tumor responses to preoperative CRT were
      assessed in terms of tumor downstaging and pathologic complete response (ypCR).
      Statistical analyses were performed to identify clinical factors associated with
      pathologic tumor response. RESULTS: Tumor downstaging was observed in 28 patients
      (54.9%), whereas ypCR was observed in 6 patients (11.8%). Multivariate analysis
      found that predictors of downstaging was pretreatment relative lymphocyte count
      (p = 0.023) and that none of clinical factors was significantly associated with
      ypCR. CONCLUSION: Pretreatment relative lymphocyte count (%) has a significant
      impact on the pathologic tumor response (tumor downstaging) after preoperative
      CRT for locally advanced rectal cancer. Enhancement of lymphocyte-mediated immune
      reactions may improve the effect of preoperative CRT for rectal cancer.

PMID- 23170289
TI  - Postoperative radiotherapy for endometrial cancer.
AB  - PURPOSE: To investigate the prognostic factors and effectiveness of postoperative
      radiotherapy alone for endometrial carcinoma. MATERIALS AND METHODS: Sixty four
      patients with stage I-III endometrial cancer (EC) treated with postoperative
      radiotherapy alone between January 1989 and December 2008 at the Keimyung
      University Dongsan Medical Center were chosen for the present study. Typically,
      total hysterectomy, salpingo-oophorectomy and lymphadenectomy were performed on
      the patient's pelvis. Total dose from 50.4 Gy to 63 Gy was irradiated at pelvis
      or extended field. Thirteen patients were treated with Co-60 or Ir-192
      intracavitary radiotherapy. Follow-up periods were from 7 to 270 months, with a
      median of 56 months. RESULTS: Five year overall survival (OS) rate was 58.7%,
      respectively. Five year disease-free survival (DFS) rate was 59.2%, respectively.
      In univariate analysis for OS and DFS, stage, menopausal age, type of operation,
      serosal invasion, and lymph node involvement were found to be statistically
      significant. Histologic type was marginally significant. In multivariate analysis
      for OS and DFS, stage, types of operation, histologic type were also found to be
      statistically significant. Treatment failure occurred in 14 patients. The main
      pattern of failure was found to be distant metastasis. Time to distant metastasis
      was from 3 to 86 months (median, 12 months). There were no grade 3 or 4
      complications. CONCLUSION: Stage, types of operation, and histologic type could
      be the predictive prognostic factors in patients. We contemplated postoperative
      radiation as effective and safe treatment method for EC. Additional treatment
      would be needed to reduce distant metastasis.

PMID- 23170290
TI  - Negative impact of pretreatment anemia on local control after neoadjuvant
      chemoradiotherapy and surgery for rectal cancer.
AB  - PURPOSE: Although anemia is considered to be a contributor to intra-tumoral
      hypoxia and tumor resistance to ionizing radiation in cancer patients, the impact
      of pretreatment anemia on local control after neoadjuvant concurrent
      chemoradiotherapy (NACRT) and surgery for rectal cancer remains unclear.
      MATERIALS AND METHODS: We reviewed the records of 247 patients with locally
      advanced rectal cancer who were treated with NACRT followed by curative-intent
      surgery. RESULTS: The patients with anemia before NACRT (36.0%, 89/247) achieved
      less pathologic complete response (pCR) than those without anemia (p = 0.012).
      The patients with pretreatment anemia had worse 3-year local control than those
      without pretreatment anemia (86.0% vs. 95.7%, p = 0.005). Multivariate analysis
      showed that pretreatment anemia (p = 0.035), pathologic tumor and nodal stage (p
      = 0.020 and 0.032, respectively) were independently significant factors for local
      control. CONCLUSION: Pretreatment anemia had negative impacts on pCR and local
      control among patients who underwent NACRT and surgery for rectal cancer.
      Strategies maintaining hemoglobin level within normal range could potentially be
      used to improve local control in rectal cancer patients.

PMID- 23170291
TI  - Treatment outcome in patients with triple negative early stage breast cancers
      compared with other molecular subtypes.
AB  - PURPOSE: To determine whether triple negative (TN) early stage breast cancers
      have poorer survival rates compared with other molecular types. MATERIALS AND
      METHODS: Between August 2000 and July 2006, patients diagnosed with stage I, II
      early stage breast cancers, in whom all three markers (estrogen receptor,
      progesterone receptor, and human epidermal growth factor receptor [HER]-2) were
      available and treated with modified radical mastectomy or breast conserving
      surgery followed by radiotherapy, were retrospectively reviewed. RESULTS: Of 446
      patients, 94 (21.1%) were classified as TN, 57 (12.8%) as HER-2 type, and 295
      (66.1%) as luminal. TN was more frequently associated with young patients younger
      than 35 years old (p = 0.002), higher histologic grade (p < 0.0001), and nuclear
      (p < 0.0001). The median follow-up period was 78 months (range, 4 to 130 months).
      There were 9 local relapses (2.0%), 15 nodal (3.4%), 40 distant metastases
      (9.0%), and 33 deaths (7.4%) for all patients. The rates of 5-year OS, DFS, LFS,
      and DMFS for all patients were 95.5%, 89.9%, 95.4%, and 91.7%, respectively.
      There were no significant differences in OS, DFS, LFS, and DMFS between triple
      negative and other subtypes (p > 0.05). CONCLUSION: We found that patients with
      TN early stage breast cancers had no difference in survival rates compared with
      other molecular subtypes. Prospective study in homogeneous treatment group will
      need for a prognosis of TN early stage breast cancer.

PMID- 23170292
TI  - Nutritional status of patients treated with radiotherapy as determined by
      subjective global assessment.
AB  - PURPOSE: The purpose of this prospective multi-institutional study was to
      evaluate the nutritional status of patients undergoing radiotherapy (RT) for
      treatment of head and neck, lung, or gastrointestinal cancer. MATERIALS AND
      METHODS: A total of 1,000 patients were enrolled in this study at seven different
      hospitals in Seoul, Korea between October 2009 and May 2010. The nutritional
      status of patients after receiving 3 weeks of RT was evaluated using subjective
      global assessment (SGA). The nutritional status of each patient was rated as well
      nourished (A), moderately malnourished (B), or severely malnourished (C).
      RESULTS: The mean age of patients in this study was 59.4 +/- 11.9 years, and the
      male to female ratio was 7:3. According to the SGA results, 60.8%, 34.5%, and
      4.7% of patients were classified as A, B, or C, respectively. The following
      criteria were significantly associated with malnutrition (SGA B or C; p < 0.001):
      loss of subcutaneous fat or muscle wasting (odds ratio [OR], 11.473); increased
      metabolic demand/stress (OR, 8.688); ankle, sacral edema, or ascites (OR, 3.234);
      and weight loss >=5% (OR, 2.299). CONCLUSION: SGA was applied successfully to
      assess the nutritional status of most patients. The prevalence of malnutrition in
      a radiation oncology department was 39.2%. The results of this study serve as a
      basis for implementation of nutrition intervention to patients being treated at
      radiation oncology departments.

PMID- 23170293
TI  - Concurrent chemoradiotherapy for elderly patients with stage III non-small cell
      lung cancer.
AB  - PURPOSE: Combined chemoradiotherapy is standard management for locally advanced
      non-small cell lung cancer (LA-NSCLC), but standard treatment for elderly
      patients with LA-NSCLC has not been confirmed yet. We evaluated the feasibility
      and efficacy of concurrent chemoradiotherapy (CCRT) for elderly patients with LA
      NSCLC. MATERIALS AND METHODS: Among patients older than 65 years with LA-NSCLC,
      36 patients, who underwent CCRT were retrospectively analyzed. Chemotherapy was
      administered 3-5 times with 4 weeks interval during radiotherapy. Thoracic
      radiotherapy was delivered to the primary mass and regional lymph nodes. Total
      dose of 54-59.4 Gy (median, 59.4 Gy) in daily 1.8 Gy fractions and 5 fractions
      per week. RESULTS: Regarding the response to treatment, complete response,
      partial response, and no response were shown in 16.7%, 66.7%, and 13.9%,
      respectively. The 1- and 2-year overall survival (OS) rates were 58.2% and 31.2%,
      respectively, and the median survival was 15 months. The 1- and 2-year
      progression-free survivals (PFS) were 41.2% and 19.5%, respectively, and the
      median PFS was 10 months. Regarding to the toxicity developed after CCRT,
      pneumonitis and esophagitis with grade 3 or higher were observed in 13.9% (5
      patients) and 11.1% (4 patients), respectively. Treatment-related death was not
      observed. CONCLUSION: The treatment-related toxicity as esophagitis and
      pneumonitis were noticeably lower when was compared with the previously reported
      results, and the survival rate was higher than radiotherapy alone. The results
      indicate that CCRT is an effective in terms of survival and treatment related
      toxicity for elderly patients over 65 years old with LA-NSCLC.

PMID- 23170294
TI  - The impact of beam angle configuration of intensity-modulated radiotherapy in the
      hepatocellular carcinoma.
AB  - PURPOSE: This treatment planning study was undertaken to evaluate the impact of
      beam angle configuration of intensity-modulated radiotherapy (IMRT) on the dose
      of the normal liver in hepatocellular carcinoma (HCC). MATERIALS AND METHODS: The
      computed tomography datasets of 25 patients treated with IMRT for HCC were
      selected. Two IMRT plans using five beams were made in each patient; beams with
      equidistance of 72 degrees  (Plan I), and beams with a 30 degrees  angle of
      separation entering the body near the tumor (Plan II). Both plans were generated
      using the same constraints in each patient. Conformity index (CI), homogeneity
      index (HI), gamma index, mean dose of the normal liver (Dmean_NL), Dmean_NL
      difference between the two plans, and percentage normal liver volumes receiving
      at least 10, 20, and 30 Gy (V10, V20, and V30) were evaluated and compared.
      RESULTS: Dmean_NL, V10, and V20 were significantly better for Plan II. The
      Dmean_NL was significantly lower for peripheral (p = 0.001) and central tumors (p
      = 0.034). Dmean_NL differences between the two plans increased in proportion to
      gross tumor volume to normal liver volume ratios (p = 0.002). CI, HI, and gamma
      indices were not significantly different for the two plans. CONCLUSION: The IMRT
      plan based on beams with narrow separations reduced the irradiated dose of the
      normal liver, which would allow radiation dose escalation for HCC.

PMID- 23170295
TI  - [Thalidomide and its legacy, the rational inside the irrational].
AB  - Thalidomide was synthesized by Chemie Grunenthal from Germany and launched at
      October 1957, as a sedative and antiemetic drug. In only four years after being
      widely and freely prescribed to pregnant women, unleashed an epidemic of
      teratogenicity that revolutionized health and public opinion. From that moment,
      world regulation on drugs and its development was radically changed, the clinical
      trial as a tool was completely revised, while pharmacovigilance as a discipline
      was established. In a second chance, its irrational use as psychotropic drug was
      changed to use as immunomodulator, context in which it is prescribed today. This
      paper aims to highlight some historical aspects of thalidomide to draw
      conclusions for rational use of psychotropic drugs.

PMID- 23170296
TI  - [Delusional disorder: clinical picture and treatment].
AB  - In 1987, the revision of the DSM-III reintroduced the concept of paranoia under
      the name of delusional disorder. Most of the actual evidence about the
      pharmacological treatment of this disorder is derived from case series and case
      reports. Antipsychotics have been used for the treatment of delusional disorder
      since 1970s, with pimozide as a first line drug. The introduction of second
      generation antipsychotics changed the treatment of the disorder. In spite of the
      available information, delusional disorder remains to this day a controversial
      and complex disorder.

PMID- 23170297
TI  - [Dysthimia or chronic depression: what do we know about its pharmacological
      treatment?].
AB  - The term dysthymia is applied to a clinical picture characterized by depressive
      feelings of low intensity and chronic evolution. Psychiatric nosology includes it
      among the mood disorders or among neurosis and personality disorders. This
      ambiguity has empirical consequences, since bibliography examining the efficacy
      of the different treatments is relatively scarce, in particular if we consider
      the incidence of the dysthymic disorder, that rounds 3% of general population. In
      this work the history of the nosology of dysthimia, the efficacy of
      pharmacological approaches and a brief mention about the efficacy of adding
      psychotherapy are summarized. Current literature indicates that antidepressants,
      independently of the group they form part of, are better than placebo, that
      maintenance treatment should be recommended and that psychotherapy could bring an
      additional benefit.

PMID- 23170298
TI  - [Psychosis and epilepsy: clinical and therapeutical approach].
AB  - Psychosis in epilepsy has generated controversy among the community of
      psychiatrists and neurologists throughout history. Currently, several
      contemporary researchers have found an increased frequency of psychosis in
      epilepsy, and identified risk factors related to the severity of epilepsy.In this
      review, we describe the main epidemiological, clinical and therapeutic issues,
      implicated in epileptic psychosis.

PMID- 23170299
TI  - [Pharmacological treatment of acute catatonia].
AB  - Catatonia is a neuropsychiatric syndrome of psychomotor dysregulation that can be
      present in a broad spectrum of clinical situations. Advances made over the last
      decades have progressively contributed to its clinical differentiation and its
      conceptual delimitation. Both Benzodiazepines (BZD) and Electroconvulsive therapy
      (ECT) have been consolidated as first-line therapy. In this regard, a BZD
      response rate ranging from 70 to 90 per cent has been reported in different case
      series. Furthermore, NMDA receptor antagonists represent an emerging strategy in
      the therapeutic approach to the disorder. Most of the evidence that supports the
      aforementioned treatment recommendations arises from descriptive observational
      studies. Traditionally, catatonia pathophysiological research focused on the
      study of subcortical brain structures. Currently there exists compelling evidence
      that supports a cortical origin of the syndrome, emphasizing the role of the
      prefrontal cortex. Neuropsychiatric catatonia models that integrate clinical,
      pathophysiological, and neurobiological findings have been postulated. The aim of
      the present review is to summarize up-to-date available evidence associated with
      the pharmacotherapeutic approach to acute catatonia as well as the neurochemical
      basis of its effectiveness. Likewise, general measures intended to prevent
      morbimortality are subject to discussion herein.

PMID- 23170300
TI  - [Pharmacological treatment of aggressive impulsive behavior].
AB  - This article makes an initially tour of the definitions of violence, aggression
      and impulsiveness. Violence is a manifestation associated with various aspects of
      human behavior in different contexts of society and history. It can also be a
      clinical manifestation of a psychiatric disorder, the behavioral modality of some
      people with personality disorders, the expression of a somatic disorder, an
      action exercised by an individual under the influence of substances, as well as
      the expected reaction of an individual or a group to a specific trigger
      situation. Aggressiveness means "tendency to act or respond violently", using
      violent means to things or people and overcome their revulsion to do damage.
      After that, a brief overview of the different classifications of aggressive
      behaviour is made, to finish reviewing the bibliography published on the
      pharmacological treatment of emotional or impulsive aggression with the three
      main groups of drugs frequently used in clinical practice (antidepressants, mood
      stabilizers and antipsychotics), and a brief integration scheme is formulated.

PMID- 23170301
TI  - [Pharmacological treatment of schizoaffective disorder, schizophreniform disorder
      and brief psychotic disorder].
AB  - This article reviews the available evidence for the pharmacological treatment of
      three of the psychotic disorders that are groupped together with schizophrenia in
      its chapter; one of them chronic -though episodic in its course- (schizoaffective
      disorder), two of them with acute symptomatology and restitutio ad integrum
      (schizophreniform disorder, brief psychotic disorder). The controversial position
      of these disorders in psychiatric nosology explains the scarce evidence for their
      pharmacological treatment. Anyhow, we shall try to stablish the main
      therapeutical approaches to these disorders.

PMID- 23170302
TI  - [Pharmacogenetics in psychiatry: how far are we from clinical application?].
AB  - Pharmacogenetics studies how genetic variation influences the response of
      patients to drugs. This discipline has a greater impact in those medical
      specialties that treat complex diseases in which the therapeutic response is
      insufficient and/or have high costs such as psychiatry. This is a narrative
      review in which we analyze the main results of pharmacogenetic studies performed
      with the most relevant groups of psychoactive drugs and discusses missing for
      incorporating these advances into our daily practice. We conclude that despite
      the remarkable progress in the field of Pharmacogenetics in the last 10 years,
      studies in psychiatry have been inconclusive and the clinical use of
      pharmacogenetic testing is still limited. However, there are some encouraging
      elements about the applicability of these tools for the improvement of
      psychiatric treatments.

PMID- 23170303
TI  - [Karl Ludwig Kahlbaum: catatonia of tension madness (1874)].

PMID- 23170304
TI  - [Catatonia or tension madness (1874)].

PMID- 23170305
TI  - The use of clobazam as an adjunctive treatment for Lennox-Gastaut syndrome.
AB  - Clobazam, a 1,5-benzodiazepine, has been available in many European countries
      since the 1970s, both as an anxiolytic and as an antiepileptic. Recently, it has
      been marketed in the U.S. for the adjunctive treatment of Lennox-Gastaut
      syndrome, a seizure disorder accompanied by mental retardation and/or learning
      difficulties. The condition is usually refractory to many antiepileptic agents.
      The pivotal phase II and III trials of adjunctive clobazam are reviewed together
      with its postulated mode of action, pharmacokinetics and drug interaction
      profile. The data are discussed in terms of existing FDA-approved agents for
      Lennox-Gastaut syndrome and suggestions for further work.

PMID- 23170306
TI  - Glucarpidase for the treatment of life-threatening methotrexate overdose.
AB  - High-dose methotrexate (HDMTX) is widely and safely used in oncology, with
      adequate measures including vigorous hydration, urine alkalinization and
      leucovorin rescue. Despite these precautions, some patients still develop HDMTX
      induced nephrotoxicity, which leads to delayed methotrexate (MTX) clearance and
      sustained elevated plasma MTX levels, which can significantly increase MTX
      toxicity. Glucarpidase (carboxypeptidase G2, Voraxase(r)) is a recombinant
      bacterial enzyme that rapidly hydrolyzes MTX to inactive metabolites, providing
      an alternate non-renal pathway for MTX elimination in patients with renal
      dysfunction during HDMTX treatment. Glucarpidase has recently been approved for
      the treatment of toxic plasma MTX concentrations in patients with delayed MTX
      clearance due to impaired renal function. Preclinical and clinical studies
      demonstrated good safety and efficacy in rapidly reducing elevated MTX levels.
      Further comparative studies are awaited to confirm the benefit of glucarpidase in
      terms of toxicity and survival.

PMID- 23170307
TI  - Pertuzumab for the treatment of patients with previously untreated HER2-positive
      metastatic breast cancer.
AB  - Pertuzumab is a humanized monoclonal antibody directed at the dimerization domain
      of the receptor tyrosine-protein kinase erbB-2 (HER2) receptor. It possesses a
      unique and complimentary mechanism of action compared to trastuzumab, which has
      historically been the cornerstone of therapy for HER2-amplified breast cancer.
      Clinical trials demonstrate improved outcomes, with minimal increases in toxicity
      with the addition of pertuzumab to trastuzumab in patients with HER2-positive
      metastatic breast cancer, indicating the advantage of dual HER2 receptor
      blockade. Pertuzumab is approved as first-line therapy in combination with
      trastuzumab and docetaxel for HER2-positive metastatic breast cancer, with future
      opportunities to investigate its efficacy in other stages of breast cancer, as
      well as in the treatment of other malignancies.

PMID- 23170308
TI  - Vandetanib therapy in medullary thyroid cancer.
AB  - The U.S. Food and Drug Administration (FDA) approved vandetanib in April 2011 for
      the treatment of unresectable, locally advanced or metastatic medullary thyroid
      cancer (MTC). In Europe it was approved in March 2012, but only for the treatment
      of aggressive and symptomatic MTC. This small molecule is a tyrosine kinase
      inhibitor of several growth factors involved in cellular proliferation and
      angiogenesis, including the epidermal growth factor receptor (EGFR) and the
      vascular endothelial growth factor receptors 2 and 3 (VEGFR-2, VEGFR-3). In
      addition, vandetanib is an inhibitor of the RET (rearranged during transfection)
      gene, a proto-oncogene often mutated in familial MTC. Since MTC is a rare
      disease, for which no previous medical therapies are approved, vandetanib is the
      first drug shown to be effective in a large phase III trial treating patients
      with metastatic or locally advanced MTC. Common adverse events are diarrhea,
      nausea, hypertension, headache and QT prolongation that are manageable and are
      commonly outweighed by the benefits of vandetanib in terms of delaying disease
      progression and inducing tumor response.

PMID- 23170309
TI  - Latest advances in biomarker discovery and development.
AB  - Oxford Global's 7th Annual Biomarkers Congress, held February 21-22, 2012, in
      Manchester (UK), gathered together approximately 300 delegates and speakers with
      a specific interest in biomarkers and their application in the field of drug
      discovery and development, as well as their enabling technologies. The audience
      and participants came from diverse and mixed backgrounds, from academicians and
      industry business professionals to representatives of solutions providers and
      CROs offering services in the field of biomarker assay development and sample
      analysis. Focus was broad, including all types of biomarkers and their
      application, i.e., prognostic and diagnostic markers, predictive markers, patient
      selection strategies in drug development, point-of-care solutions,
      pharmacodynamic and target engagement biomarkers as well as safety-related
      approaches. There were presentations spanning the entire range of biomarker
      development, from discovery to clinical qualification and analytical validation
      of a specific marker or a markers panel. A wide range of therapeutic areas were
      also covered; however, the fields of oncology and inflammatory diseases were more
      prominent, since they currently provide best case studies for biomarker discovery
      and clinical utility.

PMID- 23170310
TI  - A report from the 42nd Annual Meeting of the International Continence Society
      (October 15-19 - Beijing, China).
AB  - As Beijing was selected as the site for this year's International Continence
      Society (ICS) meeting, crowds of locals navigating through the subway train lines
      and tourists lining up for access to the Forbidden City and other landmarks were
      joined by a less numerous but a still significant number of researchers,
      scientists and practitioners working on urinary tract diseases and disorders
      going to the China National Convention Center to attend the podium and poster
      sessions. Located next to the Bird's Nest Olympic stadium and offering grand
      views over the Olympic park from the upper floor where non-discussion posters
      were displayed, the modern facilities allowed for a smooth, seamless meeting
      during which a number of highly relevant new findings were discussed. The
      following report summarizes selected presentations on pharmacotherapy and drug
      candidates for overactive bladder and other common diseases of the urinary tract.

PMID- 23170311
TI  - Effect of surface charge of PDDA-protected gold nanoparticles on the specificity
      and efficiency of DNA polymerase chain reaction.
AB  - The polymerase chain reaction (PCR) has become an indispensable technique in
      molecular biology, however, it suffers from low efficiency and specificity
      problems. Developing suitable additives to effectively avoid nonspecific PCR
      reactions and explore the mechanism for PCR enhancing is a significant challenge.
      In this paper, we report three different modified gold nanoparticles (AuNPs) with
      different surface charge polarities and poly (diallyl dimethylammonium) chloride
      (PDDA) for use as novel PCR enhancers to improve the efficiency and specificity.
      These AuNPs included the positively charged PDDA protected AuNPs (PDDA-AuNPs),
      the neutral PDDA-AuNPs modified with excess chloride ion (PDDA.C-AuNPs), and the
      negatively charged sodium citrate (Na(3)Ct) protected AuNPs (Na(3)Ct-AuNPs). Our
      data clearly suggests that the positively charged PDDA-AuNPs with an optimum
      concentration as low as 1.54 pM could significantly enhance the specificity and
      efficiency of PCR, however, the optimum concentration of the negatively charged
      Na(3)Ct-AuNPs (2.02 nM) was more than 3 orders of magnitude higher than that of
      positively charged PDDA-AuNPs. The PCR specificity and efficiency are also
      improved by the neutral PDDA.C-AuNPs with an optimum concentration, much more
      than that of the PDDA-AuNPs. This suggests that there should be an electrostatic
      interaction between the positively charged PDDA-AuNPs and the negatively charged
      PCR components, and the surface charge polarities of PDDA-AuNPs may play an
      important role in improving the PCR specificity and efficiency.

PMID- 23170746
TI  - Cardiac autonomic adaptations in elite Spanish soccer players during preseason.
AB  - PURPOSE: The purpose of this study was to evaluate changes in autonomic control
      of heart rate (HR) and fitness in a group of elite soccer players during the
      preseason. METHODS: Eight professional male soccer players competing in the
      Spanish First Division were evaluated in July (wk 1) and September (wk 8) with
      night-time HR variability (HRV) over 4 different days, ultra-short-term HR
      recovery (HRR) during a small-sided-games session, Yo-Yo Intermittent Recovery
      test level 1 (Yo-Yo IR1), and a field test for determination of maximum aerobic
      speed. RESULTS: Players exhibited a greater HRV and a faster ultra-short-term HRR
      at wk 8, with the players with a lower HRV at wk 1 exhibiting the greatest
      improvements at wk 8. However, there were unclear improvements in performance
      parameters, with maximum HR (HRmax) being reduced over the preseason period. This
      change in HRmax was correlated with the change in short-term HRV parameters (rho
      = 0.829, P = .042). Large correlations were observed among HRV, ultra-short-term
      HRR, and field performance parameters only at wk 8. Furthermore, the variation
      (%) of the root-mean-square of successive differences between R-R intervals was
      increased during the preseason (12.95% +/- 15.14% to 29.39% +/- 21.93%, P = .013)
      and significantly correlated (r = .898, P = .006) with Yo-Yo IR1 performance
      (~2600 +/- 786 m) at wk 8. CONCLUSIONS: The current results support the
      appropriateness and practicality of night-time HRV and ultra-short-term HRR for
      evaluation of autonomic adaptations in professional soccer players, despite the
      unclear improvements in specific field performance parameters.

PMID- 23170747
TI  - Influence of neuromuscular fatigue on accelerometer load in elite Australian
      football players.
AB  - PURPOSE: To determine the impact of neuromuscular fatigue (NMF) assessed from
      variables obtained during a countermovement jump on exercise intensity measured
      with triaxial accelerometers (load per minute [LPM]) and the association between
      LPM and measures of running activity in elite Australian Football. METHODS:
      Seventeen elite Australian Football players performed the Yo-Yo Intermittent
      Recovery Test level 2 (Yo-Yo IR2) and provided a baseline measure of NMF (flight
      time:contraction time [FT:CT]) from a countermovement jump before the season.
      Weekly samples of FT:CT, coaches' rating of performance (votes), LPM, and percent
      contribution of the 3 vectors from the accelerometers in addition to high-speed
      running meters per minute at >15 km/h and total distance relative to playing time
      (m/min) from matches were collected. Samples were divided into fatigued and
      nonfatigued groups based on reductions in FT:CT. Percent contributions of vectors
      to LPM were assessed to determine the likelihood of a meaningful difference
      between fatigued and nonfatigued groups. Pearson correlations were calculated to
      determine relationships between accelerometer vectors and running variables,
      votes, and Yo-Yo IR2 score. RESULTS: Fatigue reduced the contribution of the
      vertical vector by (mean +/- 90% CI) -5.8% +/- 6.1% (86% likely) and the number
      of practically important correlations. CONCLUSIONS: NMF affects the contribution
      of individual vectors to total LPM, with a likely tendency toward more running at
      low speed and less acceleration. Fatigue appears to limit the influence of the
      aerobic and anaerobic qualities assessed via the Yo-Yo IR2 test on LPM and seems
      implicated in pacing.

PMID- 23170749
TI  - Physiological and performance responses to a preseason altitude-training camp in
      elite team-sport athletes.
AB  - PURPOSE: Little research has been done on the physiological and performance
      effects of altitude training on team-sport athletes. Therefore, this study
      examined changes in 2000-m time-trial running performance (TT), hemoglobin mass
      (Hbmass), and intramuscular carnosine content of elite Australian Football (AF)
      players after a preseason altitude camp. METHODS: Thirty elite AF players
      completed 19 days of living and training at either moderate altitude (~2130 m;
      ALT, n = 21) or sea level (CON, n = 9). TT performance and Hbmass were assessed
      preintervention (PRE) and postintervention (POST1) in both groups and at 4 wk
      after returning to sea level (POST2) in ALT only. RESULTS: Improvement in TT
      performance after altitude was likely 1.5% (+/- 4.8-90%CL) greater in ALT than in
      CON, with an individual responsiveness of 0.8%. Improvements in TT were
      maintained at POST2 in ALT. Hbmass after altitude was very likely increased in
      ALT compared with CON (2.8% +/- 3.5%), with an individual responsiveness of 1.3%.
      Hbmass returned to baseline at POST2. Intramuscular carnosine did not change in
      either gastrocnemius or soleus from PRE to POST1. CONCLUSIONS: A preseason
      altitude camp improved TT performance and Hbmass in elite AF players to a
      magnitude similar to that demonstrated by elite endurance athletes undertaking
      altitude training. The individual responsiveness of both TT and Hbmass was
      approximately half the group mean effect, indicating that most players gained
      benefit. The maintenance of running performance for 4 wk, despite Hbmass
      returning to baseline, suggests that altitude training is a valuable preparation
      for AF players leading into the competitive season.

PMID- 23170750
TI  - Planned intensity reduction to maintain repetitions within recommended
      hypertrophy range.
AB  - PURPOSE: The authors tested different loading schemes for the number of
      repetitions completed during multiple sets of resistance exercise. METHODS:
      Twenty-four resistance-trained men (age 24.0 +/- 4.5 y, body mass 78.3 +/-10.2
      kg, height 177 +/- 7 cm) were tested over a 5-wk period. During week 1 a 10
      repetition maximum (10RM) in the leg press was determined. During weeks 2-5
      subjects completed 4 bouts of leg presses, in a randomized fashion, consisting of
      4 sets with 60 s of interset rest. Set 1 of each bout was performed with 10RM,
      with differing intensity for sets 2-4 as follows: (1) 10RM load for all sets
      (CON), (2) 5% load reduction after each set (RED 5), (3) 10% load reduction after
      each set (RED 10), and (4) 15% load reduction after each set (RED 15). RESULTS:
      Significant (P < .05) decreases in repetitions completed across sets were
      observed in CON (sets 2, 3, and 4) and RED 5 (sets 3 and 4). Significant
      increases in repetitions completed across sets (2, 3, and 4) were observed in RED
      10 and RED 15 (P < .05). RED 5 (8.3 +/- 0.9 repetitions) and RED 10 (12.0 +/- 1.1
      repetitions) allowed subjects to maintain the majority (>60%) of sets in the
      range of 8-12 repetitions, whereas both CON and RED 15 resulted in <50% of sets
      in the range of 8-12 repetitions, with the majority of sets performed <8
      repetitions for CON and >12 repetitions for RED 15. CONCLUSION: Reducing load 5
      10% in each set should allow maintenance of 8-12RM loads for most sets of
      resistance exercise.

PMID- 23170751
TI  - Anti-Inflammatory Effect of Exercise, Via Reduced Leptin Levels, in Obese Women
      with Down Syndrome.
AB  - Recent studies have reported that obese young people with Down syndrome suffer
      from low-grade systemic inflammation. Whereas this condition may be improved in
      the general population by regular exercise, the problem has received no attention
      in the case of people with intellectual disability. Therefore, our aim was to
      assess the influence of aerobic training on plasma adipokines in obese women with
      Down syndrome. Twenty obese young women with Down syndrome volunteered for this
      study, eleven of whom were randomly assigned to a 10-week aerobic training
      programme. They attended 3 sessions/week, which consisted of warm-up exercises
      followed by the main activity on a treadmill (30-40 min) at a work intensity of
      55-65% of peak heart rate, and ended with a cooling-down period. The control
      group included 9 women with Down syndrome matched for age, sex and BMI. Fat mass
      percentage and distribution were measured and plasma adipokine levels (leptin and
      adiponectin) were assessed. In addition, each participant performed a maximal
      graded continuous treadmill exercise test. These parameters were assessed pre-
      and post-intervention. This protocol was approved by an Institutional Ethics
      Committee. Aerobic training produced a significant increase in participants'
      VO2max (20.2+/-5.8vs.23.7+/-6.3ml/kg/min;p<0.001), and plasma leptin levels were
      significantly reduced in the intervention group (54.2+/-6.7vs.45.7+/
      6.1ng/ml;p=0.026). Further significant correlations between plasma leptin and
      indices of obesity were found. In contrast, no significant changes were found in
      adiponectin levels (p>0.05). None of tested parameters changed in the control
      group. In conclusion, a 10-week training programme reduced leptin levels in obese
      young women with Down syndrome.

PMID- 23170752
TI  - Comparison of older adults' steps per day using NL-1000 pedometer and two GT3X+
      accelerometer filters.
AB  - The purpose of this study was to compare the steps/d derived from the ActiGraph
      GT3X+ using the manufacturer's default filter (DF) and low-frequency-extension
      filter (LFX) with those from the NL-1000 pedometer in an older adult sample.
      Fifteen older adults (61-82 yr) wore a GT3X+ (24 hr/day) and an NL-1000 (waking
      hours) for 7 d. Day was the unit of analysis (n = 86 valid days) comparing (a)
      GT3X+ DF and NL-1000 steps/d and (b) GT3X+ LFX and NL-1000 steps/d. DF was highly
      correlated with NL-1000 (r = .80), but there was a significant mean difference (
      769 steps/d). LFX and NL-1000 were highly correlated (r = .90), but there also
      was a significant mean difference (8,140 steps/d). Percent difference and
      absolute percent difference between DF and NL-1000 were -7.4% and 16.0%,
      respectively, and for LFX and NL-1000 both were 121.9%. Regardless of filter
      used, GT3X+ did not provide comparable pedometer estimates of steps/d in this
      older adult sample. 

PMID- 23170753
TI  - Cardiovascular responses during downhill treadmill walking at self-selected
      intensity in older adults.
AB  - Cardiovascular responses of older adults to downhill (DTW, -10% incline) and
      level treadmill walking (0%) at self-selected walking speed (SSWS) were examined.
      Fifteen participants (age 68 +/- 4 yr, height 1.69 +/- 0.08 m, body mass 74.7 +/-
      8.1 kg) completed two 15-min walks at their SSWS (4.6 +/- 0.6 km/hr).
      Cardiovascular responses were estimated using an arterial-volume finger clamp and
      infrared plethysmography. Oxygen consumption was 25% lower during DTW and
      associated with lower values for stroke volume (9.9 ml/beat), cardiac output (1.0
      L/min), arteriovenous oxygen difference (a-v O2 diff, 2.4 ml/L), and systolic
      blood pressure (10 mmHg), with no differences in heart rate or diastolic and mean
      arterial blood pressure. Total peripheral resistance (TPR) was higher (2.11 mmHg)
      during DTW. During downhill walking, an exercise performed with reduced cardiac
      strain, endothelial changes, and reduced metabolic demand may be responsible for
      the different responses in TPR and a-v O2 diff. Future work is warranted on
      whether downhill walking is suitable for higher risk populations. 

PMID- 23170754
TI  - Fear of falling and balance ability in older men: the priest study.
AB  - Studies examining fear of falling among older adult men remain limited. The
      objectives of this study were to compare balance confidence in 2 age cohorts of
      older clergy and identify predictive determinants of balance confidence in a
      liturgical research initiative. Participants included 131 community-dwelling
      Roman Catholic priests age 60-97 yr living in religious communities in 10 mid
      Atlantic states. Subjects completed the Activities-specific Balance Confidence
      Scale (ABC), Berg Balance Scale (BBS), timed up-and-go (TUG) test, and 15-item
      Geriatric Depression Scale (GDS). Younger priests (60-74 yr) demonstrated a
      significantly higher ABC score than the older cohort (75 and above yr) of priests
      (89.1 +/- 12.6 vs.78.4 +/- 13.9, p = .001). Confidence was significantly
      correlated with BBS (rho = .69, p < .01), TUG (r = -.58, p < .01), and GDS (r = 
      .39, p < .01) scores. A stepwise-regression model demonstrated that balance
      ability, mood, assistive-device use, and physical activity predicted 52% of the
      variance in balance confidence. 

PMID- 23170755
TI  - Exploring socioecological correlates of active living in retirement village
      residents.
AB  - This study explored individual, social, and built environmental attributes in and
      outside of the retirement village setting and associations with various active
      living outcomes including objectively measured physical activity, specific
      walking behaviors, and social participation. Residents in Perth, Australia (N =
      323), were surveyed on environmental perceptions of the village and surrounding
      neighborhood, self-reported physical activity, and demographic characteristics
      and wore accelerometers. Managers (N = 32) were surveyed on village
      characteristics, and objective neighborhood measures were generated in a
      Geographic Information System (GIS). Results indicated that built- and social
      environmental attributes within and outside of retirement villages were
      associated with active living among residents; however, salient attributes varied
      depending on the specific outcome considered. Findings suggest that locating
      villages close to destinations is important for walking and that locating them
      close to previous and familiar neighborhoods is important for social
      participation. Further understanding and consideration into retirement village
      designs that promote both walking and social participation are needed. 

PMID- 23170756
TI  - Older black women's experiences initiating and maintaining physical activity:
      implications for theory and practice.
AB  - Using a semistructured discussion guide, the authors conducted 15 interviews with
      physically active older black women living in the eastern U.S. to examine what
      contributed to their physical activity initiation and maintenance. They used
      thematic analysis to organize content and constant-comparison methods to compare
      themes between participants. Participants initiated physical activity when a cue
      to action, such as weight gain or a medical issue, triggered a perceived need to
      exercise. When participants initiated physical activity, they experienced
      immediate unexpected benefits such as improved energy. They reported continuing
      activity because of these initial benefits. After continued physical activity
      over time, participants experienced the health benefits they originally hoped to
      achieve. Most participants also mentioned continuing physical activity because it
      is "me time." All participants reported needing to modify their physical activity
      routine at some point. Having a regular, yet adaptable, routine and planning
      skills helped participants maintain physical activity. These findings contribute
      to the refinement of theory and might be useful for professionals promoting
      physical activity among older black women.

PMID- 23170757
TI  - Differences in effectiveness of the active living every day program for older
      adults with arthritis.
AB  - OBJECTIVE: The authors explored whether demographic and psychosocial variables
      predicted differences in physical activity for participants with arthritis in a
      trial of Active Living Every Day (ALED). METHOD: Participants (N = 280) from 17
      community sites were randomized into ALED or usual care. The authors assessed
      participant demographic characteristics, self-efficacy, outcome expectations,
      pain, fatigue, and depressive symptoms at baseline and physical activity
      frequency at 20-wk follow-up. They conducted linear regression with interaction
      terms (Baseline Characteristic * Randomization Group). RESULTS: Being female (p
      <= .05), less depressed (p <= .05), or younger (p <= .10) was associated with
      more frequent posttest physical activity for ALED participants than for those
      with usual care. Higher education was associated with more physical activity for
      both ALED and usual-care groups. DISCUSSION: ALED was particularly effective for
      female, younger, and less depressed participants. Further research should
      determine whether modifications could produce better outcomes in other subgroups.

PMID- 23170758
TI  - Adsorption of beryllium atoms and clusters both on graphene and in a bilayer of
      graphite investigated by DFT.
AB  - We herein investigate the interaction of beryllium with a graphene sheet and in a
      bilayer of graphite by means of periodic DFT calculations. In all cases, we find
      the beryllium atoms to be more weakly bonded on graphene than in the bilayer.
      Be(2) forms both magnetic and non-magnetic structures on graphene depending on
      the geometrical configuration of adsorption. We find that the stability of the
      Be/bilayer system increases with the size of the beryllium clusters inserted into
      the bilayer of graphite. We also find a charge transfer from beryllium to the
      graphite layers. All these results are analysed in terms of electronic structure.

PMID- 23170759
TI  - Abstracts of the 5th European Public Health Conference All Inclusive Public
      Health. Portomaso, St. Julian's, Malta. November 8-10, 2012.

PMID- 23170760
TI  - [Abstracts of the 40th Annual Meeting of the Austrian Diabetes Society. November
      15-17, 2012. Salzburg, Austria].

PMID- 23170761
TI  - Abstracts of the Irish Thoracic Society Annual Scientific Meeting. November 23
      24, 2012. Limerick, Ireland.

PMID- 23170762
TI  - Maximise your chances to hit the jackpot.

PMID- 23170763
TI  - Alfentanil: correlations between absence of effect upon subcutaneous mast cells
      and absence of granuloma formation after intrathecal infusion in the dog.
AB  - BACKGROUND: We hypothesize that intrathecal (IT) granulomas arising from the IT
      infusion of several opiates may result from the degranulation of meningeal mast
      cells (MC). Given functional covariance between cutaneous and meningeal MC, we
      propose that opioids that do not degranulate cutaneous MC will not produce a
      granuloma. An opioid meeting this criteria is the phenylpiperadine alfentanil
      HCl. METHODS: Three experiments were accomplished in dogs. 1) Cutaneous MC
      degranulation. Flare areas on the dog abdomen were measured after intradermal
      alfentanil, morphine, or compound 48-80. 2) Dose ranging of analgesic effects of
      IT alfentanil infusion. Dogs with lumbar IT catheters received continuous
      infusion for 24 hours of different concentrations (1-20 mg/mL/d) of alfentanil
      and analgesic effects were assessed. 3) Granuloma inducing effects. Dogs received
      IT alfentanil (20 mg/mL/d; N = 5; 22-28 days) or morphine (12 mg/mL/d; N = 3; 22
      30 days) and spinal cord harvested for histopathology after 22-30 days of
      infusion. RESULTS: 1) Intradermal morphine (10 mg/mL) and compound 48-80 (1
      mg/mL) but not alfentanil at concentrations up to 20 mg/mL produced a cutaneous
      flare. IT alfentanil infusion produced increases in thermal escape latency at
      concentrations as low as 2 mg/mL/day. A significant depression of arousal was
      noted in the dogs receiving 20 mg/mL. Over the 22- to 30-day infusion period,
      morphine (12 mg/mL/day) resulted in granulomas in all three animals examined
      whereas IT alfentanil at 20 mg/mL/day failed to initiate a granuloma in any
      animal. CONCLUSIONS: These results support the hypothesis linking MC
      degranulation and IT granulomas.

PMID- 23170764
TI  - Influence of Zn(II) on the adsorption of arsenate onto ferrihydrite.
AB  - Addition of iron oxide to arsenic-contaminated soil has been proposed as a means
      of reducing the mobility of arsenic in the soil. Arsenic and zinc are common
      coexisting contaminants in soils. The presence of zinc therefore may affect the
      adsorption properties of arsenic on iron oxide, and may thus affect its mobility
      in the soil. The influence of Zn(II) on the adsorption of arsenate ions on iron
      oxide was studied. Batch adsorption experiments indicated that Zn(II) increased
      the arsenate removal from a solution by ferrihydrite at pH 8. However, ATR-FTIR
      spectroscopy showed that no adsorption of arsenate on a ferrihydrite film
      occurred at pD 8 in the presence of Zn(II). Precipitation of zinc hydroxide
      carbonate followed by arsenate adorption onto the precipitate was found to be a
      plausible mechanism explaining the arsenate removal from a solution in the
      presence of Zn(II) at pH/pD 8. The previously suggested mechanisms attributing
      the enhanced removal of arsenate from solution in the presence of Zn(II) to
      additional adsorption on iron oxides could not be verified under the experimental
      conditions studied. It was also shown that at pH/pD 4, the presence of Zn(II) in
      the system did not significantly affect the adsorption of arsenate on
      ferrihydrite.

PMID- 23170766
TI  - Carbon nanotubes press-transferred on PMMA substrates as exclusive transducers
      for electrochemical microfluidic sensing.
AB  - Novel single-walled carbon nanotube press-transfer electrodes (SW-PTEs) for
      microfluidic sensing are proposed. In this approach, carbon nanotubes are press
      transferred on poly(methyl methacrylate) (PMMA) substrates and are easily coupled
      to microfluidic chips and act as the exclusive transducer in electrochemical
      sensing. The detector design consisted of a press-transferred SW film (7 mm * 1
      mm) positioned and centered on the PMMA substrate (33 mm * 9 mm). The analytical
      performance of the SW-PTEs was deeply evaluated using two commercial SWs sources
      and employing a mixture of dopamine and catechol as model analytes. Analyte
      detection was influenced by the volume of commercial SW dispersion used in the
      fabrication of SW-PTEs, with 5 mL taken from a dispersion of 0.5 mg/100 mL being
      the most favorable volume. In addition, excellent repeatability (relative
      standard deviation (RSD) of <=7%, n = 5), interelectrodes reproducibility (RSD <=
      9%, n = 5), and an extreme resistance to fouling were obtained even after 1 h of
      microchip analysis with RSD values of <=4% and <=9% (n = 15) for migration times
      and peak heights, respectively. Good sensitivity, remarkable signal-to-noise
      characteristics, and a well-defined linear concentration dependence (r >= 0.990)
      was also obtained, which allowed these novel detectors to be considered as
      valuable tools for quantitative analysis. Analytical characterization of the SW
      PTEs by field-emission scanning electron microscopy (FESEM) revealed individual
      bundles of SWs that were highly ordered over the PMMA at the background where the
      SW bundles were embedded on the PMMA substrate, giving the electrode a high
      stability. Furthermore, the laboratory-fabricated SW-PTEs can be afforded in any
      laboratory since they do not require clean-room facilities and are highly
      compatible with microfluidic scale, mass production, and disposability. In
      addition, the proposed approach draws new and exciting horizons for
      electrochemical microfluidic sensing, such as the use of other pure or hybrid
      nanomaterials and also the possibilities to incorporate biomolecules for highly
      selective sensing.

PMID- 23170765
TI  - Bath salts components mephedrone and methylenedioxypyrovalerone (MDPV) act
      synergistically at the human dopamine transporter.
AB  - BACKGROUND AND PURPOSE: Bath salts is the street name for drug combinations that
      contain synthetic cathinone analogues, among them possibly mephedrone (MEPH) and
      certainly methylenedioxypyrovalerone (MDPV). In animal studies, cathinone and
      certain cathinone analogues release dopamine (DA), similar to the action of
      amphetamine (AMPH) and methamphetamine (METH). AMPH and METH act on the human DA
      transporter (hDAT); thus, we investigated MEPH and MDPV acting at hDAT.
      EXPERIMENTAL APPROACH: We recorded electrical currents mediated by hDAT expressed
      in Xenopus laevis oocytes and exposed to: DA, METH, a known hDAT stimulant and DA
      releaser, MEPH, MDPV, MEPH + MDPV, or cocaine, a known hDAT inhibitor. KEY
      RESULTS: DA, METH and MEPH induce an inward current (depolarizing) when the
      oocyte is held near the resting potential (-60 mV), therefore acting as
      excitatory hDAT substrates. Structurally analogous MDPV induces an outward
      (hyperpolarizing) current similar to cocaine, therefore acting as an inhibitory
      non-substrate blocker. CONCLUSIONS AND IMPLICATIONS: Two components of bath
      salts, MEPH and MDPV, produce opposite effects at hDAT that are comparable with
      METH and cocaine, respectively. In our assay, MEPH is nearly as potent as METH;
      however, MDPV is much more potent than cocaine and its effect is longer lasting.
      When applied in combination, MEPH exhibits faster kinetics than MDPV, viz., the
      MEPH depolarizing current occurs seconds before the slower MDPV hyperpolarizing
      current. Bath salts containing MEPH (or a similar drug) and MDPV might then be
      expected initially to release DA and subsequently prevent its reuptake via hDAT.
      Such combined action possibly underlies some of the reported effects of bath
      salts abuse.

PMID- 23170767
TI  - Plant strategies for survival in changing environment.

PMID- 23170770
TI  - Catastrophic health care spending and impoverishment in Kenya.
AB  - BACKGROUND: Many health systems in Africa are funded primarily through out-of
      pocket payments. Out-of-pocket payments prevent people from seeking care, can
      result to catastrophic health spending and lead to impoverishment. This paper
      estimates the burden of out-of-pocket payments in Kenya; the incidence and
      intensity of catastrophic health care expenditure and the effect of health
      spending on national poverty estimates. METHODS: Data were drawn from a
      nationally representative health expenditure and utilization survey (n = 8414)
      conducted in 2007. The survey provided detailed information on out-of-pocket
      payments and consumption expenditure. Standard data analytical techniques were
      applied to estimate the incidence and intensity of catastrophic health
      expenditure. Various thresholds were applied to demonstrate the sensitivity of
      catastrophic measures. RESULTS: Each year, Kenyan households spend over a tenth
      of their budget on health care payments. The burden of out-of-pocket payments is
      highest among the poor. The poorest households spent a third of their resources
      on health care payments each year compared to only 8% spent by the richest
      households. About 1.48 million Kenyans are pushed below the national poverty line
      due to health care payments. CONCLUSIONS: Kenyans are becoming poorer due to
      health care payments. The need to protect individuals from health care related
      impoverishment calls for urgent reforms in the Kenyan health system. An important
      policy question remains what health system reforms are needed in Kenya to ensure
      that financial risk protection for all is achieved.

PMID- 23170771
TI  - Saliva: a 'solubilizer' of lipophilic antioxidant polyphenols.

PMID- 23170772
TI  - De novo characterization of the banana root transcriptome and analysis of gene
      expression under Fusarium oxysporum f. sp. Cubense tropical race 4 infection.
AB  - BACKGROUND: Bananas and plantains (Musa spp.) are among the most important crops
      in the world due to their nutritional and export value. However, banana
      production has been devastated by fungal infestations caused by Fusarium
      oxysporum f. sp. cubense (Foc), which cannot be effectively prevented or
      controlled. Since there is very little known about the molecular mechanism of Foc
      infections; therefore, we aimed to investigate the transcriptional changes
      induced by Foc in banana roots. RESULTS: We generated a cDNA library from total
      RNA isolated from banana roots infected with Foc Tropical Race 4 (Foc TR 4) at
      days 0, 2, 4, and 6. We generated over 26 million high-quality reads from the
      cDNA library using deep sequencing and assembled 25,158 distinct gene sequences
      by de novo assembly and gap-filling. The average distinct gene sequence length
      was 1,439 base pairs. A total of 21,622 (85.94%) unique sequences were annotated
      and 11,611 were assigned to specific metabolic pathways using the Kyoto
      Encyclopedia of Genes and Genomes database. We used digital gene expression (DGE)
      profiling to investigate the transcriptional changes in the banana root upon Foc
      TR4 infection. The expression of genes in the Phenylalanine metabolism,
      phenylpropanoid biosynthesis and alpha-linolenic acid metabolism pathways was
      affected by Foc TR4 infection. CONCLUSION: The combination of RNA-Seq and DGE
      analysis provides a powerful method for analyzing the banana root transcriptome
      and investigating the transcriptional changes during the response of banana genes
      to Foc TR4 infection. The assembled banana transcriptome provides an important
      resource for future investigations about the banana crop as well as the diseases
      that plague this valuable staple food.

PMID- 23170773
TI  - The utilization of antenatal care among rural-to-urban migrant women in Shanghai:
      a hospital-based cross-sectional study.
AB  - BACKGROUND: Improving utilization of antenatal care is a critical strategy for
      achieving China's Millennium Development Goal of decreasing the maternal
      mortality ratio (MMR). While overall utilization has increased recently in China,
      an urban vs. rural disparity in access remains. Here we aim to assess utilization
      of antenatal care in rural-to-urban migrant women and identify its risk and
      protective factors. METHODS: Migrant women who had been living in Shanghai for
      more than six months, delivered in one of the two study hospitals between August
      2009 and February 2010, and provided written consent were interviewed using a
      structured questionnaire. RESULTS: Of 767 women, 90.1% (691) made at least one
      antenatal care visit, while 49.7% (381) had adequately utilized antenatal care
      (i.e., made five or more antenatal care visits). Only 19.7% of women visited an
      antenatal care center during the first trimester (12 weeks). Women between the
      ages of 25 and 30 and women older than 30 were more likely than younger women to
      have adequately utilized antenatal care (AOR=2.2 and 1.9, 95%CI=1.4-3.5 and 1.1
      3.2, respectively). Women whose husbands held Shanghai residency status (AOR=4.9,
      95%CI=2.2-10.9) or who had more than 10 years of education (AOR=1.8, 95%CI=1.2
      2.9), previously experienced a miscarriage or abortion (AOR=2.2, 95%CI=1.3-3.8),
      had higher household income (AOR=1.6, 95%CI=1.0-2.5) were more likely to have
      adequately utilized antenatal care. Women from high-income households were also
      more likely to receive antenatal care during the first 12 weeks (AOR=3.5,
      95%CI=1.7-5.5). CONCLUSIONS: Many migrant women in Shanghai did not receive
      adequate antenatal care and initiated antenatal care later than the optimal first
      12 weeks of pregnancy. Poor antenatal care utilization was associated with low
      socioeconomic status, education, and certain demographic factors. Tailored health
      education for both migrant women and their husbands should be strengthened to
      improve maternal health. Financing supports should be provided to improve the
      utilization of antenatal care.

PMID- 23170774
TI  - Seasonal variation in abiotic factors and ferulic acid toxicity in snail
      attractant pellets against the intermediate host snail Lymnaea acuminata.
AB  - Laboratory evaluation was made to access the seasonal variations in abiotic
      environmental factors temperature, pH, dissolved oxygen, carbon dioxide,
      electrical conductivity and ferulic acid toxicity in snail-attractant pellets
      (SAP) against the intermediate host snail Lymnaea acuminata in each month of the
      years 2010 and 2011. On the basis of a 24-h toxicity assay, it was noted that
      lethal concentration values of 4.03, 3.73% and 4.45% in SAP containing starch and
      4.16, 4.23% and 4.29% in SAP containing proline during the months of May, June
      and September, respectively, were most effective in killing the snails, while SAP
      containing starch/proline + ferulic acid was least effective in the month of
      January/February (24-h lethal concentration value was 7.67%/7.63% in SAP). There
      was a significant positive correlation between lethal concentration value of
      ferulic acid containing SAP and levels of dissolved O2 /pH of water in
      corresponding months. On the contrary, a negative correlation was observed
      between lethal concentration value and dissolved CO2 /temperature of test water
      in the same months. To ascertain that such a relationship between toxicity and
      abiotic factors is not co-incidental, the nervous tissue of treated (40% and 80%
      of 24-h lethal concentration value) and control group of snails was assayed for
      the activity of acetylcholinesterase (AChE) in each of the 12 months of the same
      year. There was a maximum inhibition of 58.43% of AChE, in snails exposed to 80%
      of the 24-h lethal concentration value of ferulic acid + starch in the month of
      May. This work shows conclusively that the best time to control snail population
      with SAP containing ferulic acid is during the months of May, June and September.

PMID- 23170775
TI  - Juniperolide A: a new polyketide isolated from a terrestrial actinomycete,
      Streptomyces sp.
AB  - A new linear polyketide, juniperolide A (1), was produced by the terrestrial
      actinomycete (Lv1-48) isolated from the rhizosphere of the plant Juniperus
      excelsa. The juniperolide A (1) structure contains a THP unit and a 3-amino-2,3,6
      trideoxyhexose as the glycosidic moiety. Mosher's analysis was used for absolute
      stereochemistry determinations at C-2, C-8, C-20, and C-4', while the relative
      stereochemistry assignments of the remaining stereocenters were based on ROESY
      correlations and J-based coupling.

PMID- 23170776
TI  - Kefir immobilized on corn grains as biocatalyst for lactic acid fermentation and
      sourdough bread making.
AB  - The natural mixed culture kefir was immobilized on boiled corn grains to produce
      an efficient biocatalyst for lactic acid fermentation with direct applications in
      food production, such as sourdough bread making. The immobilized biocatalyst was
      initially evaluated for its efficiency for lactic acid production by fermentation
      of cheese whey at various temperatures. The immobilized cells increased the
      fermentation rate and enhanced lactic acid production compared to free kefir
      cells. Maximum lactic acid yield (68.8 g/100 g) and lactic acid productivity
      (12.6 g/L per day) were obtained during fermentation by immobilized cells at 37 
      degrees C. The immobilized biocatalyst was then assessed as culture for sourdough
      bread making. The produced sourdough breads had satisfactory specific loaf
      volumes and good sensory characteristics. Specifically, bread made by addition of
      60% w/w sourdough containing kefir immobilized on corn was more resistant
      regarding mould spoilage (appearance during the 11(th)  day), probably due to
      higher lactic acid produced (2.86 g/Kg of bread) compared to the control samples.
      The sourdough breads made with the immobilized biocatalyst had aroma profiles
      similar to that of the control samples as shown by headspace SPME GC-MS analysis.

PMID- 23170777
TI  - Improvement in the breakdown properties of electrowetting using polyelectrolyte
      ionic solution.
AB  - We report the improvement in the breakdown properties of electrowetting using a
      mixture of poly(acrylic acid)  (PAA) polyelectrolyte and a surfactant (Tween 80,
      TW80). Onset of  breakdown was initially determined via visual observation and
      further verified by investigating impedance phase shift. Breakdown
      characteristics of the large-molecule ionic solution were compared with those of
      conventional electrolytes (Na(2)SO(4)) that produce small molecules. Experiments
      with various conductivities and hydrophobic coatings on a thin silicon nitride
      dielectric layer (~500 A) showed that the breakdown voltage of the PAA-TW80
      system was at least two times higher than that of the Na(2)SO(4)-TW80 system. Our
      results demonstrate that defects in the dielectric and hydrophobic layers are
      less vulnerable to larger ionic molecules.

PMID- 23170779
TI  - Ethical considerations in clinical trials: a critique of the ICH-GCP guideline.
AB  - This article examines issues relating to ethics decision-making in clinical
      trials. The overriding concern is to ensure that the well being and the interests
      of human subjects are adequately safeguarded. In this respect, this article will
      embark on a critical analysis of the ICH-GCP Guideline. The purpose of such an
      undertaking is to highlight areas of concern and the shortcomings of the existing
      ICH-GCP Guideline. Particular emphasis is made on how ethics committees perform
      their duties and responsibilities in line with the principles outlined in the ICH
      GCP Guideline. This article will draw attention to the need for a new approach to
      addressing the weaknesses of the ICH-GCP Guideline in its present form. 

PMID- 23170778
TI  - Crystal structures of murine angiogenin-2 and -3-probing 'structure--function'
      relationships amongst angiogenin homologues.
AB  - Angiogenin (Ang) is a potent inducer of neovascularization. Point mutations in
      human Ang have been linked to cancer progression and two neurodegenerative
      diseases: amyotrophic lateral sclerosis and Parkinson's disease. Intensive
      structural and functional analyses of Ang have been paramount in assigning
      functions to this novel homologue of bovine pancreatic RNase A. However,
      inhibitor-binding studies with crystalline Ang (for designing potential anti
      cancer drugs) have been hampered as a result of the inaccessibility of the active
      site. Experiments with the murine homologues of Ang have not only overcome the
      obvious practical limitations encountered when studying the role of a human
      protein in healthy individuals, but also the crystal structures of murine
      angiogenins (mAng and mAng-4) have revealed themselves to have greater potential
      for the visualization of small-molecule inhibitor binding at the active site. In
      the present study, we report the crystal structures of two more murine Ang
      paralogues, mAng-2 and mAng-3, at 1.6 and 1.8 A resolution, respectively. These
      constitute the first crystal structures of an Ang with a zinc ion bound at the
      active site and provide some insight into the possible mode of inhibition of the
      ribonucleolytic activity of the enzyme by these divalent cations. Both structures
      show that the residues forming the putative P(1), B(1) and B(2) subsites occupy
      positions similar to their counterparts in human Ang and are likely to have
      conserved roles. However, a less obtrusive conformation of the C-terminal segment
      in mAng-3 and the presence of a sulfate ion in the B(1) subsite of mAng-2 suggest
      that these proteins have the potential to be used for inhibitor-binding studies.
      We also discuss the biological relevance of the structural similarities and
      differences between the different Ang homologues.

PMID- 23170780
TI  - 'Sustaining Place' - a grounded theory of how informal carers of people with
      dementia manage alterations to relationships within their social worlds.
AB  - AIMS AND OBJECTIVES: This paper presents a theory explaining the processes used
      by informal carers of people with dementia to mange alterations to their, and
      people with dementias' relationships with and places within their social worlds.
      BACKGROUND: Informal carers provide the majority of care to people with dementia.
      A great deal of international informal dementia care research is available, much
      of which elucidates the content, impacts and consequences of the informal caring
      role and the coping mechanisms that carers use. However, the socially situated
      experiences and processes integral to informal caring in dementia have not yet
      been robustly accounted for. DESIGN: A classic grounded theory approach was used
      as it is designed for research enquiries that aim to generate theory illustrating
      social patterns of action used to address an identified problem. METHODS: Thirty
      interviews were conducted with 31 participants between 2006-2008. The theory was
      conceptualised from the data using the concurrent methods of theoretical
      sampling, constant comparative analysis, memo writing and theoretical
      sensitivity. RESULTS: Informal carers' main concern was identified as 'Living on
      the fringes', which was stimulated by dementia-related stigma and living a
      different life. The theory of 'Sustaining Place' explains the social pattern of
      actions employed by informal carers to manage this problem on behalf of
      themselves and the person with dementia. CONCLUSIONS: The theory of 'Sustaining
      Place' identifies an imperative for nurses, other formal carers and society to
      engage in actions to support and enable social connectedness, social inclusion
      and citizenship for informal carers and people with dementia. RELEVANCE TO
      CLINICAL PRACTICE: 'Sustaining Place' facilitates enhanced understanding of the
      complex and socially situated nature of informal dementia care through its
      portrayal of informal carers as social agents and can be used to guide nurses to
      better support those who live with dementia.

PMID- 23170781
TI  - Off-axis partial coherence interferometry in myopes and emmetropes.
AB  - PURPOSE: This study describes the axial and peripheral dimensions of myopic and
      emmetropic eyes in a wide range of retinal locations using a non-contact optical
      biometer (Zeiss IOLMaster) based upon the principle of partial coherence
      interferometry. Understanding the optical properties of the peripheral eye may
      provide insight into myopia development and the possible effects on off-axis
      visual performance. METHODS: Fifty-two myopes (spherical equivalent between -2.00
      and -9.62 D) and 27 emmetropes (spherical equivalent between -0.50 and +0.50 D)
      with astigmatism less than 0.75 D, participated in this study. Axial length and
      peripheral cornea to retina lengths were measured using partial coherence
      interferometry at the fovea and up to +/- 30 degrees  eccentricity along the
      horizontal and vertical meridian in 10 degrees  steps. Relative cornea to retina
      length was calculated by subtracting the axial length from that obtained at each
      peripheral location. RESULTS: Our results showed significant differences between
      refractive groups for both horizontal (p < 0.001) and vertical (p < 0.001)
      meridians, illustrating that the retinal shape profile is significantly different
      between myopes and emmetropes. Myopic eyes exhibited a greater rate of change in
      cornea to retina lengths with increasing eccentricity than emmetropic eyes, with
      the temporal portion of the retina exhibiting the steepest shift. In addition,
      significant nasal-temporal asymmetry was observed, which was more pronounced in
      myopic eyes. CONCLUSIONS: Axial and peripheral cornea to retina dimension
      measurements, using partial coherence interferometry, suggest that myopic eyes
      tend toward an ellipsoid shape compared to the spherical emmetropic eyes.

PMID- 23170782
TI  - Gout and subsequent increased risk of cardiovascular mortality in non-diabetics
      aged 50 and above: a population-based cohort study in Taiwan.
AB  - BACKGROUND: Limited data are available on the risk ratios for fatal
      cardiovascular disease (CVD) outcome from gout and chronic kidney disease (CKD)
      in non-diabetic individuals. METHODS: Nationwide population-based retrospective
      prospective study with a 5-year follow-up to investigate the association between
      physician-diagnosed gout and CKD in non-diabetics aged 50 and above who had no
      pre-existing serious CVD and the subsequent risk of death from CVD. Hazard ratios
      (HR) of CVD mortality were adjusted for gender, age, smoking- and alcoholism
      related diagnoses, hypertension, hyperlipidemia, atrial fibrillation and
      Charlson's comorbidity index score. RESULTS: A case cohort (n=164,463) having
      gout and a control cohort (n=3,694,377) having no gout were formed. The
      prevalence of gout in this study was 4.26% whereas that of gout plus CKD was
      8.17%. Male to female ratio among the individuals with gout was 3.2:1. The
      relative risk (RR) of subsequent cardiovascular mortality between the case and
      control cohort was 1.71 (95% confidence interval (CI), 1.66-1.75). The presence
      of CKD in nondiabetic subjects with no gout (control group) has a RR of CVD
      mortality at 3.05 (95% CI, 2.94-3.15). The presence of gout has protective effect
      on subjects with CKD with a RR of 1.84 (95% CI, 1.71-1.98). As compared with
      individuals with no gout, the adjusted HR (aHR) for CVD mortality among the
      individuals with gout was 1.10 (95% CI 1.07-1.13). In a Cox model, when compared
      with subjects having neither gout nor CKD, the aHR in subjects with no gout but
      with CKD is 1.76 (95% CI, 1.70-1.82); in subjects with gout but without CKD, 1.10
      (1.07-1.13); interestingly, the aHR is attenuated in subjects with concomitant
      gout plus CKD which is 1.38 (1.29-1.48). CONCLUSIONS: Among non-diabetic
      individuals aged 50 years or above who had no preceding serious CVD, those with
      gout were 1.1 times more likely to die from CVD as were individuals without gout.
      The presence of gout appears to attenuate the risk of subsequent CV mortality in
      subjects with CKD. Further studies should focus on finding an explanation for the
      protective effect of gout on CV mortality in patients with CKD.

PMID- 23170783
TI  - Importance of cognitive assessment as part of the "Kihon Checklist" developed by
      the Japanese Ministry of Health, Labor and Welfare for prediction of frailty at a
      2-year follow up.
AB  - AIM: To investigate which category in the "Kihon Checklist" developed by the
      Japanese Ministry of Health, Labor and Welfare can predict functional decline for
      community-dwelling elderly people at a 2-year follow up. METHOD: We compared
      comprehensive geriatric assessment (CGA) between "specified elderly individuals"
      at high risk of requiring long-term care insurance (LTCI) and "uncertified
      elderly people" (neither certified under LTCI nor "specified"), and also compared
      CGA between the risk group and non-risk group, in subcategories of the "Kihon
      Checklist", such as physical strength, nutrition/oral function, overall low score
      on questions 1-20, houseboundness, cognitive function, and depression risk. The
      study population consisted of 527 elderly participants aged 75 years and older in
      a cross-sectional study, and 382 in a longitudinal study. CGA was assessed for
      basic and higher functional activities of daily living (ADL), depressive
      symptoms, and quality of life (QOL). The Student's t-test was used in the cross
      sectional study and ANOVA with repeated measures was used in the longitudinal
      analysis. RESULTS: In the cross-sectional study, the risk group had lower
      functions in all CGA items than the non-risk group in all subcategories of the
      "Kihon Checklist." In the longitudinal study, Tokyo Metropolitan Institute of
      Gerontology Index of Competence scores and its three subscales declined in the
      risk group both in physical and cognitive subcategories compared with the non
      risk group, whereas only one or two subscales of Tokyo Metropolitan Institute of
      Gerontology Index of Competence declined in "specified" and the other two
      subcategories of the Kihon Checklist CONCLUSION: In both cross-sectional and
      longitudinal studies, the assessment of physical strength and cognitive function
      was more useful to detect frail elderly.

PMID- 23170784
TI  - Lipid mediators in plasma of autism spectrum disorders.
AB  - BACKGROUND: Inflammation is increasingly recognized as being of both
      physiological and pathological importance in the immature brain. Cerebellar
      pathology occurs in autism, as a neurodevelopmental disorder with genetic and
      environmental origins. The genesis of this disorder is still not understood but
      inflammation in utero or early in childhood is an environmental risk factor.
      METHODS: Prostaglandin E2 (PGE2), cysteinyl leukotriene as two important lipid
      mediators together with 8 isoprostane as marker of oxidative stress were measured
      using ELISA in plasma of 20 male autistic patients compared to 19 age and gender
      matching control participants. RESULTS: PGE2, leukotrienes and isoprostanes
      recorded significantly elevated levels in autistics compared to controls. Role of
      these measured parameters in inflammation and autoimmunity as two etiological
      factors in autism were discussed in details. CONCLUSION: Receiver Operating
      Characteristic (ROC) curve analysis shows satisfactory values of area under the
      curve (AUC) which could reflect the high degree of specificity and sensitivity of
      the altered PGE2, leukotrienes and isoprostanes as predictive biomarkers in
      autistic patients from Saudi Arabia.

PMID- 23170785
TI  - Acculturation and gestational weight gain in a predominantly Puerto Rican
      population.
AB  - BACKGROUND: Identifying risk factors that affect excess weight gain during
      pregnancy is critical, especially among women who are at a higher risk for
      obesity. The goal of this study was to determine if acculturation, a possible
      risk factor, was associated with gestational weight gain in a predominantly
      Puerto Rican population. METHODS: We utilized data from Proyecto Buena Salud, a
      prospective cohort study of Hispanic women in Western Massachusetts, United
      States. Height, weight and gestational age were abstracted from medical records
      among participants with full-term pregnancies (n=952). Gestational weight gain
      was calculated as the difference between delivery and prepregnancy weight.
      Acculturation (measured via a psychological acculturation scale, generation in
      the US, place of birth and spoken language preference) was assessed in early
      pregnancy. RESULTS: Adjusting for age, parity, perceived stress, gestational age,
      and prepregnancy weight, women who had at least one parent born in Puerto
      Rico/Dominican Republic (PR/DR) and both grandparents born in PR/DR had a
      significantly higher mean total gestational weight gain (0.9 kg for at least one
      parent born in PR/DR and 2.2 kg for grandparents born in PR/DR) and rate of
      weight gain (0.03 kg/wk for at least one parent born in PR/DR and 0.06 kg/wk for
      grandparents born in PR/DR) vs. women who were of PR/DR born. Similarly, women
      born in the US had significantly higher mean total gestational weight gain (1.0
      kg) and rate of weight gain (0.03 kg/wk) vs. women who were PR/ DR born. Spoken
      language preference and psychological acculturation were not significantly
      associated with total or rate of pregnancy weight gain. CONCLUSION: We found that
      psychological acculturation was not associated with gestational weight gain while
      place of birth and higher generation in the US were significantly associated with
      higher gestational weight gain. We interpret these findings to suggest the
      potential importance of the US "obesogenic" environment in influencing unhealthy
      pregnancy weight gains over specific aspects of psychological acculturation.

PMID- 23170786
TI  - Experimental therapy for lung cancer: umbilical cord-derived mesenchymal stem
      cell-mediated interleukin-24 delivery.
AB  - The use of adult stem cells as gene delivery vehicles is a novel and attractive
      strategy for cancer therapy. Mesenchymal stem cells (MSCs) provide a promising
      source for stem cell-based gene therapies. Interleukin-24 (IL24) has been
      suggested as an effective anticancer agent. However, a lack of tumor-targeted
      delivery and a host immune response to viral vehicles has hindered its
      application for cancer therapy. In this study, we evaluated the effects of IL24
      delivered by MSCs as a therapeutic approach for lung cancer. We engineered human
      umbilical cord-derived MSCs (UC-MSCs) to efficiently deliver secretable IL24. We
      observed that IL24-transduced UC-MSCs (IL24-MSCs) inhibited the growth of A549
      lung cancer cells by induction of apoptosis and cell cycle arrest. The IL24
      proteins secreted by IL24-MSCs were involved in regulating the ERK-1/2, AKT and
      JNK signaling pathways. Additionally, MSCs-mediated IL24 expression led to an
      increase in the cleavage of caspases-3/8/9 and PARP, the Bax/Bcl-2 ratio, as well
      as the p21 expression in A549 cells. We also demonstrated that injection of IL24
      MSCs significantly suppressed xenograft tumor growth. Moreover, the IL24-MSCs had
      anti-angiogenic effects both in vitro and in vivo. Taken together, our findings
      indicate that IL24 delivered by human UC-MSCs has the potential to be used as an
      alternative strategy for lung cancer therapy.

PMID- 23170787
TI  - Clinical and forensic signs related to opioids abuse.
AB  - For a good performance in Clinical and Forensic Toxicology it is important to be
      aware of the biological and non-biological signs and symptoms related to
      xenobiotic exposure. This manuscript highlights and analyzes clinical and
      forensic imaging related to opioids abuse critically. Particularly, respiratory
      depression, track marks and hemorrhages, skin "popping", practices of phlebotomy,
      tissue necrosis and ulceration, dermatitis, tongue hyperpigmentation, "coma
      blisters", intra-arterial administration, candidiasis, wounds associated with
      anthrax or clostridium contaminated heroin, desomorphine related lesions and
      characteristic non-biological evidences are some commonly reported findings in
      opioids abuse, which will be discussed. For this purpose, clinical and forensic
      cases from our database (National Institute of Legal Medicine and Forensic
      Sciences, North Branch, Portugal), in addition to literature data, are reviewed.

PMID- 23170788
TI  - Does the use of fetal fibronectin in an algorithm for preterm labor reduce triage
      evaluation times?
AB  - OBJECTIVE: To determine the effectiveness of a novel algorithm based on fetal
      fibronectin (FFN) for management of preterm labor (PTL). METHODS: A randomized
      trial was performed on patients who presented with symptoms of PTL at 24-34
      weeks. Patients were randomized to algorithms with cervical exams only versus
      cervical exams plus FFN. In this algorithm, physicians had to discharge patients
      with a negative FFN result. The primary outcome was the evaluation time for
      triage. The secondary outcomes were admission to the hospital for PTL, preterm
      birth <34 weeks and preterm birth <37 weeks. RESULTS: A total of 76 patients were
      enrolled and randomized (control n = 32, FFN n = 44). There were no differences
      in triage time, hospital admissions or preterm deliveries (PTDs) between the two
      groups. CONCLUSION: An algorithm based on FFN for management of PTL does not
      reduce evaluation times for triage, hospital admissions or PTDs.

PMID- 23170789
TI  - Factor VIIa regulates the expression of caspase-3, MMP-9, and CD44 in SW620 colon
      cancer cells involving PAR2/MAPKs/NF-kappaB signaling pathways.
AB  - Our previous study has demonstrated that TF/FVIIa and PAR2 are closely related to
      the proliferation and migration of colon cancer cell line SW620. However, the
      detailed molecular mechanisms in the process remain unclear. This study further
      investigated whether some important molecules (caspase-3, MMP-9 and CD44) are
      involved in the events. The results showed that PAR2-AP or FVIIa elicited time
      dependent downregulation of caspase-3, and up-regulation of MMP-9 and CD44 in
      SW620 cells. The effects of FVIIa were TF-dependent and involving PAR2/MAPKs/NF
      kappaB signal transduction pathways. Our study suggests that the links among
      PAR2/MAPKs/NF-kappaB may be blocked for effective treatments of colorectal
      cancers.

PMID- 23170790
TI  - The role of psychological resilience and positive affect in risky decision
      making.
AB  - Past studies suggest that positive affect produces a wide range of desirable
      outcomes because it helps people build lasting resources. It may be assumed that
      these resources build on positive affect over time, which in turn may explain the
      beneficial effect of positive affect in stressful encounters. However, this
      assumption has not been directly tested by empirical studies. This question is
      important in that it helps clarify the underlying mechanism through which
      individuals with more positive affect might respond adaptively to adverse
      situations. Using a stressful task that included 20 rounds of risky investment
      choices, the current study examined whether psychological resilience, an
      important personal resource fuelled by positive affect, could account for the
      beneficial effects of positive affect. Specifically, we examined the relationship
      between individuals' baseline levels of positive affect, their levels of
      psychological resilience, their choices in a risky investment decision task, and
      their levels of positive affect on the final investment task. The results
      demonstrate that psychological resilience could indeed help explain happier
      people's enhanced outcomes: They chose higher return although more risky
      investment options and experienced more positive affect at the end of the task.
      The current study supports the notion that individuals who experience frequent
      positive affect thrive through various challenges not simply because they feel
      good, but because they have resources that they can utilize to deal with these
      challenges. Findings from the present study support further investigation of the
      important relationship between specific positive affect, psychological
      resilience, and performance in risky investment tasks. 

PMID- 23170791
TI  - Editorial: neuroprotection and neuroregeneration in ischemic stroke: emerging
      treatment strategies and potential molecular targets.

PMID- 23170792
TI  - Stroke prevention: from available antiplatelet drugs to novel molecular targets.
AB  - Stroke is the third most common cause of death in the industrialized countries
      and adequate primary and secondary prevention strategies are mandatory. In
      addition to lifestyle-changes and correction of cardiovascular risk factors, the
      mainstay of the atherothrombotic stroke prevention is represented by antiplatelet
      treatment. Although aspirin and thienopyridines have proved their efficacy in the
      prevention of arterial thrombotic events, limited efficacy, increased risk of
      bleeding, significant inter-individual variability in the response and extended
      duration of action that cannot be reversed if the need for haemostasis or
      emergency surgery arises represent major limitations of these drugs. Moreover,
      despite recommendations and guidelines about stroke prevention, registries data
      clearly suggest an underuse of antiplatelet drugs, mainly because of bleeding
      episodes fear. At variance with newer anticoagulant drugs, which showed a series
      of advantages as compared with the traditional warfarin treatment, newer
      antiplatelet drugs have only partially overcome these limitations. Although ad
      hoc studies on their efficacy in the stroke prevention are currently lacking,
      newer antiplatelet agents (mainly ticagrelor and prasugrel) do not provide a
      significant better protection over and above aspirin and/or clopidogrel in the
      prevention of atherothrombotic stroke. In addition, a significantly increased
      bleeding risk has been reported in subjects receiving these new thienopyridines.
      According to these data, the identification of further molecular targets is
      needed, in order to design future antiplatelet drugs. In this review, after
      summarizing major literature data about traditional and newer antiplatelet drugs,
      we will specifically focus on novel potential target candidates for antiplatelet
      therapy.

PMID- 23170793
TI  - Oxidation inhibits iron-induced blood coagulation.
AB  - Blood coagulation under physiological conditions is activated by thrombin, which
      converts soluble plasma fibrinogen (FBG) into an insoluble clot. The structure of
      the enzymatically-generated clot is very characteristic being composed of thick
      fibrin fibers susceptible to the fibrinolytic degradation. However, in chronic
      degenerative diseases, such as atherosclerosis, diabetes mellitus, cancer, and
      neurological disorders, fibrin clots are very different forming dense matted
      deposits (DMD) that are not effectively removed and thus create a condition known
      as thrombosis. We have recently shown that trivalent iron (ferric ions) generates
      hydroxyl radicals, which subsequently convert FBG into abnormal fibrin clots in
      the form of DMDs. A characteristic feature of DMDs is their remarkable and
      permanent resistance to the enzymatic degradation. Therefore, in order to prevent
      thrombotic incidences in the degenerative diseases it is essential to inhibit the
      iron-induced generation of hydroxyl radicals. This can be achieved by the
      pretreatment with a direct free radical scavenger (e.g. salicylate), and as shown
      in this paper by the treatment with oxidizing agents such as hydrogen peroxide,
      methylene blue, and sodium selenite. Although the actual mechanism of this
      phenomenon is not yet known, it is possible that hydroxyl radicals are
      neutralized by their conversion to the molecular oxygen and water, thus
      inhibiting the formation of dense matted fibrin deposits in human blood.

PMID- 23170795
TI  - A key role for connexin hemichannels in spreading ischemic brain injury.
AB  - Brain damage resulting from cerebral ischemia remains a significant problem at
      all stages of life. In adults, ischemic stroke is the third leading cause of
      death and the leading cause of disability in the developed world. In term
      newborns, moderate to severe brain damage after hypoxia-ischemia (HI) occurs in 1
      3 per 1000 live births. One of the most striking features of HI injury is that
      after initial recovery of cellular oxidative metabolism, there is a delayed,
      'secondary' mitochondrial failure that spreads over time from the most severely
      damaged areas outwards, into previously undamaged regions. This secondary failure
      is accompanied by transient seizure activity and cytotoxic edema. The specific
      mechanisms of this spread are poorly understood, but it is at least partly
      associated with spreading waves of depression that can trigger cell death in
      neighboring uninjured tissues. The waves are propagated through cell-cell
      communication via gap junction channels (the so called "bystander effect"). It
      has recently been proposed that unopposed connexin hemichannels (connexons) also
      play a significant role by mediating release of paracrine molecules that in turn
      propagate cell death messages by releasing intracellular mediators such as ATP,
      NAD(+), or glutamate or by abnormally prolonged opening to allow cell edema.
      There is increasing evidence that connexin hemichannels contribute to injury
      after many neural insults and that it is possible to significantly reduce the
      spread of damage after injury by suppressing the induction or activity of the
      connexin proteins that form hemichannels.

PMID- 23170796
TI  - Minocycline mediated mitochondrial cytoprotection: premises for therapy of
      cerebrovascular and neurodegenerative diseases.
AB  - In the last decades, emerging molecular targets for ischemic neuroprotection and
      regeneration have been postulated. This fact allowed that classical drugs with
      well established therapeutic applications might be used in cerebrovascular
      diseases as well as neurodegenerative diseases. Minocycline is a commonly used
      antibiotic of the tetracycline family (7-dimethylamino-6-dimethyl-6
      deoxytetracycline) which reveals cytoprotective capability and potential use in
      treatment of different diseases. Here, we discuss the literature concerning
      minocycline. The available data indicate that the antibiotic has multi-faceted
      effects on cell functions and, consequently, a number of clinical properties that
      are useful and/or could be useful for treatment of different diseases including
      bacterial infections, cancer, autoimmune disorders, ischemia as well as
      neurodegenerative and psychiatric diseases. Thus, application of minocycline as a
      therapeutic agent is the subject of clinical trials for various diseases. It is
      also evident that minocycline-mediated cytoprotection, including neuroprotection,
      is an important aspect of its clinical application. Here, we have reviewed the
      basis of the minocycline activity as well as different studies indicating that
      minocycline can be used as potential therapeutic agent in both cerebrovascular
      and neurodegenerative diseases in human.

PMID- 23170797
TI  - Inhalation gases or gaseous mediators as neuroprotectants for cerebral ischaemia.
AB  - Ischaemic stroke is one of the leading causes of morbidity and mortality
      worldwide. While recombinant tissue plasminogen activator can be administered to
      produce thrombolysis and restore blood flow to the ischaemic brain, therapeutic
      benefit is only achieved in a fraction of the subset of patients eligible for
      fibrinolytic intervention. Neuroprotective therapies attempting to restrict the
      extent of brain injury following cerebral ischaemia have not been successfully
      translated into the clinic despite overwhelming pre-clinical evidence of
      neuroprotection. Therefore, an adequate treatment for the majority of acute
      ischaemic stroke patients remains elusive. In the stroke literature, the use of
      therapeutic gases has received relatively little attention. Gases such as
      hyperbaric and normobaric oxygen, xenon, hydrogen, helium and argon all possess
      biological effects that have shown to be neuroprotective in pre-clinical models
      of ischaemic stroke. There are significant advantages to using gases including
      their relative abundance, low cost and feasibility for administration, all of
      which make them ideal candidates for a translational therapy for stroke. In
      addition, modulating cellular gaseous mediators including nitric oxide, carbon
      monoxide, and hydrogen sulphide may be an attractive option for ischaemic stroke
      therapy. Inhalation of these gaseous mediators can also produce neuroprotection,
      but this strategy remains to be confirmed as a viable therapy for ischaemic
      stroke. This review highlights the neuroprotective potential of therapeutic gas
      therapy and modulation of gaseous mediators for ischaemic stroke. The therapeutic
      advantages of gaseous therapy offer new promising directions in breaking the
      translational barrier for ischaemic stroke.

PMID- 23170798
TI  - Neuroprotection & mechanism of ethanol in stroke and traumatic brain injury
      therapy: new prospects for an ancient drug.
AB  - Effective efforts to screen for agents that protect against the devastating
      effects of stroke have not produced viable results thus far. As a result this
      article reviews the possible role of ethanol as a neuroprotective agent in stroke
      and traumatic brain injury (TBI). Previous studies have associated ethanol
      consumption with a decreased risk of ischemic stroke, suggesting a
      neuroprotective mechanism. The translation of this clinical knowledge into basic
      science research with the goal of new therapy for acute stroke patients remains
      in its initial stages. In a recent study involving rats, we have shown that
      ethanol administration, in the correct dose after stroke onset, protects against
      ischemia-induced brain injury. The purpose of this paper is to discuss ethanol's
      neuroprotective properties in stroke when consumed as a preconditioning agent, in
      TBI with a positive blood alcohol content, and finally in stroke treatment, with
      the goal of using post-ischemia ethanol (PIE) therapy to ameliorate brain damage
      in the future.

PMID- 23170799
TI  - Stem cell-mediated gene delivering for the treatment of cerebral ischemia:
      progress and prospectives.
AB  - Ischemic stroke is one of the leading causes of death and disability worldwide.
      There is no effective treatment for ischemic stroke apart from thrombolytic
      therapy, which has a narrow therapeutic time window. Gene therapy has proven to
      be effective in experimental stroke, but it suffers from disadvantages that limit
      its clinical application, such as difficulty in intracranial delivering of
      therapeutic genes, low efficacy in transfecting host cells and long-term
      expression of exogenous genes. Delivering therapeutic genes to the ischemic brain
      via stem cells is an alternative strategy of combined gene and stem cell therapy.
      There are advantages for stem cell-mediated gene delivery as opposed to direct
      gene transfer. In recent years, studies used stem cells that over-express
      different neurotrophic factors, such as BDNF, GDNT, or NT3, and found that the
      delivery of these genetically-modified stem cells to animal models of ischemic
      stroke is safe and effective, thus suggesting that stem cell-based gene therapy
      may be a promising treatment for stroke. This review summarizes the advantages
      and recent progress of stem cell-based gene therapy for ischemic stroke. We also
      discuss the relevant strategy for optimizing stem cell-based gene therapy and
      discuss the potential strategies for its future application.

PMID- 23170794
TI  - Global cerebral ischemia: synaptic and cognitive dysfunction.
AB  - Cardiopulmonary arrest is one of the leading causes of death and disability,
      primarily occurring in the aged population. Numerous global cerebral ischemia
      animal models induce neuronal damage similar to cardiac arrest. These global
      cerebral ischemia models range from vessel occlusion to total cessation of
      cardiac function, both of which have allowed for the investigation of this
      multifaceted disease and detection of numerous agents that are neuroprotective.
      Synapses endure a variety of alterations after global cerebral ischemia from the
      resulting excitotoxicity and have been a major target for neuroprotection;
      however, neuroprotective agents have proven unsuccessful in clinical trials, as
      neurological outcomes have not displayed significant improvements in patients. A
      majority of these neuroprotective agents have specific neuronal targets, where
      the success of future neuroprotective agents may depend on non-specific targets
      and numerous cognitive improvements. This review focuses on the different models
      of global cerebral ischemia, neuronal synaptic alterations, synaptic
      neuroprotection and behavioral tests that can be used to determine deficits in
      cognitive function after global cerebral ischemia.

PMID- 23170802
TI  - Pain monitoring in anesthetized children: first assessment of skin conductance
      and analgesia-nociception index at different infusion rates of remifentanil.
AB  - BACKGROUND: Analgesia and nociception can not be specifically monitored during
      general anesthesia. Movement of the patient or hemodynamic variations are usually
      considered as symptoms of insufficient analgesia. The measure of skin conductance
      (SC) allows an assessment of peripheral sympathetic activity. The analgesia
      nociception index (ANI) provides an evaluation of the parasympathetic activity
      based on heart rate variability. These two non-invasive monitors might allow a
      better assessment of perioperative nociception. OBJECTIVES: Describe the profiles
      of SC and ANI after a standardized nociceptive stimulation, in anesthetized
      children, at different infusion rates of remifentanil. MATERIALS/METHODS: For
      this pilot study, 12 children (8.4 +/- 5 years) scheduled for middle-ear surgery
      were anesthetized with desflurane to maintain a bispectral index at 50.
      Remifentanil was used for analgesia, at an initial infusion rate of 0.2 MUg.kg(
      1) .min(-1) . Remifentanil infusion rate was then decreased: Five steady-state
      periods of 10 min were obtained at 0.2, 0.16, 0.12, 0.08, and 0.04 MUg.kg(-1)
      .min(-1) . At the end of each period, a standardized tetanic stimulation was
      applied to the patient. Variations in heart rate, blood pressure, SC, and ANI
      were recorded before and after each stimulation. RESULTS: After the stimulation,
      ANI was significantly decreased compared with prestimulation values for all
      remifentanil infusion rates. This decrease was greater at 0.04 MUg.kg(-1) .min(
      1) than at the other infusion rates. SC, heart rate, and blood pressure were not
      modified by the stimulations, whatever the dose of remifentanil. CONCLUSION: ANI
      might provide a more sensitive assessment of nociception in anesthetized children
      than hemodynamic parameters or skin conductance.

PMID- 23170800
TI  - microRNAs: innovative targets for cerebral ischemia and stroke.
AB  - Stroke is one of the leading causes of death and disability worldwide. Because
      stroke is a multifactorial disease with a short therapeutic window many clinical
      stroke trials have failed and the only currently approved therapy is
      thrombolysis. MicroRNAs (miRNA) are endogenously expressed noncoding short single
      stranded RNAs that play a role in the regulation of gene expression at the post
      transcriptional level, via degradation or translational inhibition of their
      target mRNAs. The study of miRNAs is rapidly growing and recent studies have
      revealed a significant role of miRNAs in ischemic disease. miRNAs are especially
      important candidates for stroke therapeutics because of their ability to
      simultaneously regulate many target genes and since to date targeting single
      genes for therapeutic intervention has not yet succeeded in the clinic. Although
      there are already quite a few review articles about miRNA in ischemic heart
      disease, much less is currently known about miRNAs in cerebral ischemia. This
      review summarizes current knowledge about miRNAs and cerebral ischemia, focusing
      on the role of miRNAs in ischemia, both changes in expression and identification
      of potential targets, as well as the potential of miRNAs as biomarkers and
      therapeutic targets in cerebral ischemia.

PMID- 23170803
TI  - Reliability and internal consistency of questionnaire for evaluating weight
      cycling in Southern Brazil.
AB  - AIMS AND OBJECTIVES: To determine the reliability and internal consistency of a
      questionnaire that was designed to assess weight cycling. BACKGROUND: A large
      part of the obese population attempt to lose weight. Of those who had lost at
      least 10% of their initial weight, 33.5% regained weight. This weight loss and
      regain is termed 'weight cycling'. So far, no available validated instruments
      exist that are capable of identifying these patients. DESIGN: A quantitative
      study for the validation of a questionnaire. METHODS: The selected patients
      received a phone call from the researchers. On that occasion, they answered a
      questionnaire that contained eight questions about their current weight, their
      weight at 18 years of age and their history of weight cycling over the past two
      years. Approximately 20 days after the first phone call, the patients were re
      contacted and asked to respond again to the proposed questionnaire. The internal
      consistency and reliability were examined through a kappa index and a chi-squared
      test. The questions that showed evidence of reliability and consistency composed
      the final questionnaire. RESULTS: The final questionnaire consisted of six
      questions. An analysis of the test-retest kappa coefficient was moderate or
      greater for four of the six objective questions. One of the two quantitative
      questions showed a strong correlation for the test/retest reliability, and the
      other showed a strong correlation with the gold standard. An analysis of the
      internal consistency between a composition of questions 5 and 6 with question 4
      showed moderate agreement, which increased when it was adjusted for the same cut
      off point. The agreement between patients classified as 'weight cyclers' was
      higher than 80% in both tests. CONCLUSIONS: The Questionnaire to Assess Weight
      Cycling provided evidence of reliability and internal consistency. RELEVANCE TO
      CLINICAL PRACTICE: Evaluating weight cycling.

PMID- 23170801
TI  - Activated protein C ameliorates Bacillus anthracis lethal toxin-induced lethal
      pathogenesis in rats.
AB  - BACKGROUND: Lethal toxin (LT) is a major virulence factor of Bacillus anthracis.
      Sprague Dawley rats manifest pronounced lung edema and shock after LT treatments,
      resulting in high mortality. The heart failure that is induced by LT has been
      suggested to be a principal mechanism of lung edema and mortality in rodents.
      Since LT-induced death occurs more rapidly in rats than in mice, suggesting that
      other mechanisms in addition to the heart dysfunction may be contributed to the
      fast progression of LT-induced pathogenesis in rats. Coagulopathy may contribute
      to circulatory failure and lung injury. However, the effect of LT on coagulation
      induced lung dysfunction is unclear. METHODS: To investigate the involvement of
      coagulopathy in LT-mediated pathogenesis, the mortality, lung histology and
      coagulant levels of LT-treated rats were examined. The effects of activated
      protein C (aPC) on LT-mediated pathogenesis were also evaluated. RESULTS: Fibrin
      depositions were detected in the lungs of LT-treated rats, indicating that
      coagulation was activated. Increased levels of plasma D-dimer and thrombomodulin,
      and the ameliorative effect of aPC further suggested that the activation of
      coagulation-fibrinolysis pathways plays a role in LT-mediated pathogenesis in
      rats. Reduced mortality was associated with decreased plasma levels of D-dimer
      and thrombomodulin following aPC treatments in rats with LT-mediated
      pathogenesis. CONCLUSIONS: These findings suggest that the activation of
      coagulation in lung tissue contributes to mortality in LT-mediated pathogenesis
      in rats. In addition, anticoagulant aPC may help to develop a feasible
      therapeutic strategy.

PMID- 23170804
TI  - Parents' experiences of early support.
AB  - In Finland, support for families with children is given, as far as possible, as
      part of basic services. However, to support basic services, services of this kind
      have also been generated as the result of several projects. The public sector
      itself has been reorganized and reformed to more resemble a project. In this
      article, the experiences of parents with children receiving project-based support
      are studied qualitatively. Preventive support was offered via child health and
      maternity clinics in the form of home visiting. The reform of the municipal and
      service structure has made the development of preventive services an issue of
      even greater current relevance. The purpose of the study was to collect and
      explore the experiences of parents as reported in their own voices. The research
      question is, how did families experience this novel support model in practice?
      The data consist of interviews with six client families, including mothers and
      fathers, nine parents in all. A qualitative and narrative approach to the
      interview data was used. Analysis of the interviews yielded the following themes:
      being critical about the support given, building trust between parents and the
      professionals and empowering parents through support. According to the results,
      parents experienced receiving early support, and especially home visiting, as
      useful. The purpose of home visiting was not always clear to begin with, and
      consequently, some parents had reservations about them. Experiences of maternity
      and child health clinics varied. In addition to the health professionals' skills,
      their personality, familiarity and supportive and trustful way of working was
      felt to be most important. Parents felt that their parenting skills and
      relationships met with approval during the family work. Further research is
      needed on this kind of early support, especially support delivered at home, to
      develop these services. 

PMID- 23170805
TI  - Angiotensin II contractile effects in mouse colon: role for pre- and post
      junctional AT(1A)  receptors.
AB  - AIM: This study investigates whether a local renin-angiotensin system (RAS)
      exists in mouse colon and whether angiotensin II (Ang II) may play a role in the
      regulation of the contractile activity. METHODS: Isometric recordings were
      performed in vitro on the longitudinal muscle of mouse proximal and distal colon.
      Transcripts encoding for RAS components were investigated by RT-PCR. RESULTS: Ang
      II caused, in both preparations, a concentration-dependent contractile effect,
      antagonized by losartan, AT(1)  receptor antagonist, but not by PD123319, AT(2) 
      receptor antagonist. The combination of losartan plus PD123319 caused no change
      on the Ang II-induced contraction than losartan alone. Tetrodotoxin, neural
      blocker, reduced the contractile response to Ang II in the proximal colon, whilst
      the response was abolished in the distal colon. In both preparations, atropine,
      muscarinic receptor antagonist, or SR140333, NK(1)  receptor antagonist, reduced
      the Ang II responses. Ondansetron, 5-HT(3)  receptor antagonist, SR48968, NK(2) 
      receptor antagonist, or hexamethonium, nicotinic receptor antagonist, were
      ineffective. The joint application of atropine and SR140333 produced no additive
      effect. Atropine reduced NK(1) -induced contraction. Transcripts encoding RAS
      components were detected in the colon samples. However, just AT(1A)  mRNA was
      expressed in both preparations, and AT(2)  mRNA was expressed only in the distal
      colon. CONCLUSION: In the murine colon, local RAS may play a significant role in
      the control of contractile activity. Ang II positively modulates the spontaneous
      contractile activity via activation of post-junctional and pre-junctional AT(1A) 
      receptors, the latter located on the enteric neurones, modulating the release of
      tachykinins and acetylcholine.

PMID- 23170806
TI  - On abortion: exploring psychological meaning and attitudes in a sample of Mexican
      gynecologists.
AB  - Elective abortion has become an issue of ethical and political debate in many
      countries including Mexico. As gynecologists are directly involved in the
      practice of abortion, it is important to know the psychological meaning that the
      term 'elective abortion' has for them. This study explores the psychological
      meaning and attitudes toward elective abortion of one hundred and twenty-three
      Mexican gynecologists. We used the semantic networks technique, which analyzed
      the words the participants associated with the term 'elective abortion'. The
      defining words most frequently used by participants implied a negative sanction.
      There were important differences by gender and religiosity: male gynecologists,
      as well as those with strong religious beliefs (mainly Catholics), revealed a
      more negative psychological meaning and more negative attitudes than females or
      physicians with weak religious beliefs. A contribution of the present study is
      that it highlights the importance of psychology to enhancing understanding of the
      issue of elective abortion. 

PMID- 23170807
TI  - A novel amine receptor based on the binol scaffold functions as a highly
      effective chiral shift reagent for carboxylic acids.
AB  - A "smart" receptor has been newly synthesized. NMR studies demonstrated that the
      receptor functions as a chiral shift reagent that is highly effective for
      determining the enantiomeric purity of a series of carboxylic acids, particularly
      those that have an alpha-oxygen atom.

PMID- 23170808
TI  - Relationship between salivary mucin or amylase and the periodontal status.
AB  - OBJECTIVE: Here we determine the relationship between salivary levels of mucin
      and amylase and the clinical parameters of periodontal disease before and after
      periodontal treatment. SUBJECTS: Ninety two subjects were clinically examined and
      distributed into four groups namely clinically healthy, mild, moderate and severe
      periodontitis, according to the periodontal status, classified according the
      values of clinical attachment level (CAL) and probing pocket depth (PPD).
      Unstimulated saliva was collected for 5 min. Salivary proteins, amylase and mucin
      were determined by colorimetric methods. RESULTS: A significant positive
      correlation (P < 0.0001) was observed between salivary mucin, amylase or protein
      and PPD or CAL before periodontal treatment while flow rate showed a negative
      correlation. Mucin and amylase output also showed a positive correlation with PPD
      or CAL. After treatment, the improvement of clinical parameters was accompanied
      by a diminution of salivary mucin, amylase or protein concentration and output in
      moderate and severe group. CONCLUSIONS: The increment of mucin and amylase output
      in relation to periodontal status indicates that salivary glands respond to the
      disease by increasing the protective potential of saliva when necessary and
      return to the normal rate of secretion after the resolution of the inflammatory
      process.

PMID- 23170809
TI  - Quantitative proteome of medulla oblongata in spontaneously hypertensive rats.
AB  - We performed an extensive quantitative proteomic analysis on the pooled medulla
      sample of the 11-week-old spontaneously hypertensive rats (SHR) compared to age
      matched normotensive Wistar rats, using iTRAQ technology coupled with nano two
      dimentional liquid chromatography followed by high resolution mass spectrometric
      abundance indexes techniques. Many differentially expressed proteins identified
      were involved in energy metabolism, such as mitochondrial part, pyruvate
      dehydrogenase complex, and respiratory chain. These proteins were included in
      citrate cycle (TCA cycle), pyruvate metabolism and oxidative phosphorylation. The
      proteomic analysis and subsequent Western blotting on two independent cohorts of
      animials indicated that the dysregulation of energy metabolism existed in the
      medulla of the SHR rats. The differentially expressed proteins in the
      dysregulation of energy metabolism in the medulla of SHR rats included down
      regulated ATP6V1D, ATP6VOA1, ATP5L, DLD proteins and up-regulated AK1 protein.
      MAO-A protein also exhibited decreased regulation, as well as the other 3 above
      mentioned energy-relative proteins (ATP6V1D, ATP5L and DLD proteins) belonging to
      the heterocycle metabolic process. A receiver operating characteristic curve
      (ROC) analysis on 4 of the differentially expressed proteins respectively
      resulted in an area under the receiver operating characteristic curve (AUC) of
      0.95, 0.90, 0.92, and 0.81 for differentiating the SHR rats from the normotensive
      rats. This dysfunction in energy metabolism localizes to the medulla, the lower
      part of brain stem, and is, therefore, likely to contribute to the development,
      as well as to pathophysiological complications of hypertension.

PMID- 23170810
TI  - Dietary plasmalogen increases erythrocyte membrane plasmalogen in rats.
AB  - BACKGROUND: Many disorders with plasmalogen deficiency have been reported.
      Replenishment or replacement of tissue plasmalogens of these disorders would be
      beneficial to the patients with these disorders, but effects of dietary
      plasmalogen on mammals have not been reported. METHODS: Plasmalogens were
      purified from chicken skin. The purified plasmalogens consisted of 96.4%
      ethanolamine plasmalogen (PlsEtn), 2.4% choline plasmalogen (PlsCho) and 0.5%
      sphingomyelin (SM). A diet containing 0.1% the purified plasmalogens (PlsEtn
      diet) was given to rats. Relative composition of phospholipids was measured by a
      high performance liquid chromatography (HPLC) method that can separate intact
      plasmalogens and all other phospholipid classes by a single chromatographic run.
      RESULTS: The PlsEtn diet given to Zucker diabetic fatty (ZDF) rats for 4 weeks
      caused decreases of plasma cholesterol and plasma phospholipid as compared to
      control diet. The other routine laboratory tests of plasma including
      triacylglycerol, glucose, liver and renal functions, albumin, and body weight
      were not different. Relative compositions of erythrocyte PlsEtn and
      phosphatidylethanolamine (PE) increased, and that of phosphatidylcholine (PC)
      decreased in PlsEtn diet group. The PlsEtn diet given to normal rats for 9 weeks
      again caused decrease of plasma cholesterol and phospholipid, and it induced
      increase of relative composition of PlsEtn of the erythrocyte membrane. The other
      routine laboratory tests of plasma and body weight were not different.
      CONCLUSIONS: Dietary PlsEtn increases relative composition of PlsEtn of
      erythrocyte membranes in normal and ZDF rats, and it causes decreases of plasma
      cholesterol and plasma phospholipids. Dietary PlsEtn for 9 weeks seemingly causes
      no adverse effect to health of normal rats.

PMID- 23170812
TI  - Preparation of water-resistant antifog hard coatings on plastic substrate.
AB  - A novel water resistant antifog (AF) coating for plastic substrates was
      developed, which has a special hydrophilic/hydrophobic bilayer structure. The
      bottom layer, acting both as a mechanical support and a hydrophobic barrier
      against water penetration, is an organic-inorganic composite comprising colloidal
      silica embedded in a cross-linked network of dipentaethritol hexaacrylate (DPHA).
      Atop this layer, an AF coating is applied, which incorporates a superhydrophilic
      species synthesized from Tween-20 (surfactant), isophorone diisocyanate (coupling
      agent), and 2-hydroxyethyl methacrylate (monomer). Various methods, e.g., FTIR,
      SEM, AFM, contact angle, and steam test, were employed to characterize the
      prepared AF coatings. The results indicated that the size and the continuity of
      the hydrophilic domains on the top surface increased with increasing added amount
      of T20, however, at the expense of hardness, adhesiveness, and water resistivity.
      The optimal T20 content was found to be 10 wt %, at which capacity the resultant
      AF coating was transparent and wearable (5H, hardness) and could be soaked in
      water for 7 days at 25  degrees C without downgrading of its AF capability.

PMID- 23170811
TI  - Flavonone treatment reverses airway inflammation and remodelling in an asthma
      murine model.
AB  - BACKGROUND AND PURPOSE: Asthma is an inflammatory disease that involves airway
      hyperresponsiveness and remodelling. Flavonoids have been associated to anti
      inflammatory and antioxidant activities and may represent a potential therapeutic
      treatment of asthma. Our aim was to evaluate the effects of the sakuranetin
      treatment in several aspects of experimental asthma model in mice. EXPERIMENTAL
      APPROACH: Male BALB/c mice received ovalbumin (i.p.) on days 0 and 14, and were
      challenged with aerolized ovalbumin 1% on days 24, 26 and 28. Ovalbumin
      sensitized animals received vehicle (saline and dimethyl sulfoxide, DMSO),
      sakuranetin (20 mg kg(-1) per mice) or dexamethasone (5 mg kg(-1) per mice) daily
      beginning from 24th to 29th day. Control group received saline inhalation and
      nasal drop vehicle. On day 29, we determined the airway hyperresponsiveness,
      inflammation and remodelling as well as specific IgE antibody. RANTES, IL-5, IL
      4, Eotaxin, IL-10, TNF-alpha, IFN-gamma and GMC-SF content in lung homogenate was
      performed by Bioplex assay, and 8-isoprostane and NF-kB activations were
      visualized in inflammatory cells by immunohistochemistry. KEY RESULTS: We have
      demonstrated that sakuranetin treatment attenuated airway hyperresponsiveness,
      inflammation and remodelling; and these effects could be attributed to Th2 pro
      inflammatory cytokines and oxidative stress reduction as well as control of NF-kB
      activation. CONCLUSIONS AND IMPLICATIONS: These results highlighted the
      importance of counteracting oxidative stress by flavonoids in this asthma model
      and suggest sakuranetin as a potential candidate for studies of treatment of
      asthma.

PMID- 23170813
TI  - Fast determination of absolute metabolite concentrations by spatially encoded 2D
      NMR: application to breast cancer cell extracts.
AB  - Two-dimensional nuclear magnetic resonance (2D NMR) forms a powerful tool for the
      quantitative analysis of complex mixtures such as samples of metabolic relevance.
      However, its use for quantitative purposes is far from being trivial, not only
      because of the associated experiment time, but also due to its subsequent high
      sensitivity to hardware instabilities affecting its precision. In this paper, an
      alternative approach is considered to measure absolute metabolite concentrations
      in complex mixtures with a high precision in a reasonable time. It is based on a
      "multi-scan single shot" (M3S) strategy, which is derived from the ultrafast 2D
      NMR methodology. First, the analytical performance of this methodology is
      compared to the one of conventional 2D NMR. 2D correlation spectroscopy (COSY)
      spectra are obtained in 10 min on model metabolic mixtures, with a precision in
      the 1-4% range (versus 5-18% for the conventional approach). The M3S approach
      also shows a better linearity than its conventional counterpart. It ensures that
      accurate quantitative results can be obtained provided that a calibration
      procedure is carried out. The M3S COSY approach is then applied to measure the
      absolute metabolite concentration in three breast cancer cell line extracts,
      relying on a standard addition protocol. M3S COSY spectra of such extracts are
      recorded in 20 min and give access to the absolute concentration of 14 major
      metabolites, showing significant differences between cell lines.

PMID- 23170815
TI  - Autologous bone marrow-derived stem cells in wound healing.

PMID- 23170814
TI  - The Seamless Transfer-of-Care Protocol: a randomized controlled trial assessing
      the efficacy of an electronic transfer-of-care communication tool.
AB  - BACKGROUND: The transition between acute care and community care represents a
      vulnerable period in health care delivery. The vulnerability of this period has
      been attributed to changes to patients' medication regimens during
      hospitalization, failure to reconcile discrepancies between admission and
      discharge and the burdening of patients/families to take over care
      responsibilities at discharge and to relay important information to the primary
      care physician. Electronic communication platforms can provide an immediate link
      between acute care and community care physicians (and other community providers),
      designed to ensure consistent information transfer. This study examines whether a
      transfer-of-care (TOC) communication tool is efficacious and cost-effective for
      reducing hospital readmission, adverse events and adverse drug events as well as
      reducing death. METHODS: A randomized controlled trial conducted on the Medical
      Teaching Unit of a Canadian tertiary care centre will evaluate the efficacy and
      cost-effectiveness of a TOC communication tool. Medical in-patients admitted to
      the unit will be considered for this study. Data will be collected upon
      admission, and a total of 1400 patients will be randomized. The control group's
      acute care stay will be summarized using a traditional dictated summary, while
      the intervention group will have a summary generated using the TOC communication
      tool. The primary outcome will be a composite, at 3 months, of death or
      readmission to any Alberta acute-care hospital. Secondary outcomes will be the
      occurrence of post-discharge adverse events and adverse drug events at 1 month
      post discharge. Patients with adverse outcomes will have their cases reviewed by
      two Royal College certified internists or College-certified family physicians,
      blinded to patients' group assignments, to determine the type, severity,
      preventability and ameliorability of all detected adverse outcomes. An
      accompanying economic evaluation will assess the cost per life saved, cost per
      readmission avoided and cost per QALY gained with the TOC communication tool
      compared to traditional dictation summaries. DISCUSSION: This paper outlines the
      study protocol for a randomized controlled trial evaluating an electronic
      transfer-of-care communication tool, with sufficient statistical power to assess
      the impact of the tool on the significant outcomes of post-discharge death or
      readmission. The study findings will inform health systems around the world on
      the potential benefits of such tools, and the value for money associated with
      their widespread implementation. TRIAL REGISTRATION: ClinicalTrials.gov
      NCT01402609.

PMID- 23170816
TI  - Novel electronic refreshers for cardiopulmonary resuscitation: a randomized
      controlled trial.
AB  - BACKGROUND: Currently the American Red Cross requires that individuals renew
      their cardiopulmonary resuscitation (CPR) certification annually; this often
      requires a 4- to 8-hour refresher course. Those trained in CPR often show a
      decrease in essential knowledge and skills within just a few months after
      training. New electronic means of communication have expanded the possibilities
      for delivering CPR refreshers to members of the general public who receive CPR
      training. The study's purpose was to determine the efficacy of three novel CPR
      refreshers--online website, e-mail and text messaging--for improving three
      outcomes of CPR training--skill retention, confidence for using CPR and intention
      to use CPR. These three refreshers may be considered "novel" in that they are not
      typically used to refresh CPR knowledge and skills. METHODS: The study conducted
      two randomized clinical trials of the novel CPR refreshers. A mailed brochure was
      a traditional, passive refresher format and served as the control condition. In
      Trial 1, the refreshers were delivered in a single episode at 6 months after
      initial CPR training. In Trial 2, the refreshers were delivered twice, at 6 and 9
      months after initial CPR training, to test the effect of a repeated delivery.
      Outcomes for the three novel refreshers vs. the mailed brochure were determined
      at 12 months after initial CPR training. RESULTS: Assignment to any of three
      novel refreshers did not improve outcomes of CPR training one year later in
      comparison with receiving a mailed brochure. Comparing outcomes for subjects who
      actually reviewed some of the novel refreshers vs. those who did not indicated a
      significant positive effect for one outcome, confidence for performing CPR. The
      website refresher was associated with increased behavioral intent to perform CPR.
      Stated satisfaction with the refreshers was relatively high. The number of
      episodes of refreshers (one vs. two) did not have a significant effect on any
      outcomes. CONCLUSIONS: There was no consistent evidence for the superiority of
      novel refreshers as compared with a traditional mailed brochure, but the low
      degree of actual exposure to the materials does not allow a definitive
      conclusion. An online web-based approach seems to have the most promise for
      future research on electronic CPR refreshers.

PMID- 23170817
TI  - Improved quality of management of eclampsia patients through criteria based audit
      at Muhimbili National Hospital, Dar es Salaam, Tanzania. Bridging the quality
      gap.
AB  - BACKGROUND: Criteria-based audits (CBA) have been used to improve clinical
      management in developed countries, but have only recently been introduced in the
      developing world. This study discusses the use of a CBA to improve quality of
      care among eclampsia patients admitted at a University teaching hospital in Dar
      es Salaam Tanzania. OBJECTIVE: The prevalence of eclampsia in MNH is high (~6%)
      with the majority of cases arriving after start of convulsions. In 2004-2005 the
      case-fatality rate in eclampsia was 5.1% of all pregnant women admitted for
      delivery (MNH obstetric data base). A criteria-based audit (CBA) was used to
      evaluate the quality of care for eclamptic mothers admitted at Muhimbili National
      Hospital (MNH), Dar es Salaam, Tanzania after implementation of recommendations
      of a previous audit. METHODS: A CBA of eclampsia cases was conducted at MNH.
      Management practices were evaluated using evidence-based criteria for appropriate
      care. The Ministry of Health (MOH) guidelines, local management guidelines, the
      WHO manual supplemented by the WHO Reproductive Health Library, standard
      textbooks, the Cochrane database and reviews in peer reviewed journals were
      adopted. At the initial audit in 2006, 389 case notes were assessed and compared
      with the standards, gaps were identified, recommendations made followed by
      implementation. A re-audit of 88 cases was conducted in 2009 and compared with
      the initial audit. RESULTS: There was significant improvement in quality of
      patient management and outcome between the initial and re-audit: Review of
      management plan by senior staff (76% vs. 99%; P=0.001), urine for albumin test
      (61% vs. 99%; P=0.001), proper use of partogram to monitor labour (75% vs. 95%;
      P=0.003), treatment with steroids for lung maturity (2.0% vs. 24%; P=0.001),
      Caesarean section within 2 hours of decision (33% vs. 61%; P=0.005), full blood
      count (28% vs. 93%; P=0.001), serum urea and creatinine (44% vs. 86%; P=0.001),
      liver enzymes (4.0% vs. 86%; P=0.001), and specialist review within 2 hours of
      admission (25% vs. 39%; P=0.018). However, there was no significant change in
      terms of delivery within 24 hours of admission (69% vs. 63%; P=0.33). There was
      significant reduction of maternal deaths (7.7% vs. 0%; P=0.001). CONCLUSION: CBA
      is applicable in low resource setting and can help to improve quality of care in
      obstetrics including management of pre-eclampsia and eclampsia.

PMID- 23170818
TI  - In vitro activity of colistin as single agent and in combination with antifungals
      against filamentous fungi occurring in patients with cystic fibrosis.
AB  - Because published reports indicate that the antibiotic colistin (COL) has
      antifungal properties, this study investigated the antifungal in vitro activity
      of COL as single agent and in combination with the antifungal compounds
      voriconazole (VRC), caspofungin (CAS) and amphotericin B (AMB) against
      Scedosporium/Pseudallescheria spp., Exophiala dermatitidis and Geosmithia
      argillacea. In total, susceptibility was determined for 77
      Scedosporium/Pseudallescheria spp., 82 E. dermatitidis and 17 G. argillacea
      isolates. The minimal inhibitory concentrations (MICs) of COL and the antifungals
      as single compound and in combination were determined with MIC test strips. Drug
      interactions were detected by crossing the MIC test strips at a 90o angle. The
      fractional inhibitory concentration index was used to categorise the drugs'
      interaction. The MIC50 value of COL was 12 MUg ml(-1) for S. prolificans, 16 MUg
      ml(-1) for P. apiosperma, 16 MUg ml(-1) for P. boydii, 12 MUg ml(-1) for E.
      dermatiditis and 6 MUg ml(-1) for G. argillacea. VRC was the most active drug in
      combination without any antagonism with the exception of few P. boydii isolates.
      COL as single agent and in most combinations with antifungals exhibits in vitro
      antifungal activity against filamentous ascomycetes occurring in cystic fibrosis
      patients and may offer a novel therapeutic option, especially for multidrug
      resistant S. prolificans.

PMID- 23170819
TI  - The difference in C-reactive protein value between initial and 24 hours follow-up
      (D-CRP) data as a predictor of mortality in organophosphate poisoned patients.
AB  - BACKGROUND: Organophosphate poisoning is a worldwide concern and there have been
      many reports about factors involved in the severity and prognosis of toxicity.
      The aim of this study was to evaluate the relationship between the serum C
      reactive protein activity and clinical outcome in acute organophosphate-poisoned
      patients. METHODS: This was a retrospective cohort study conducted from January
      2007 to February 2012. Using a multivariate logistic analysis, data on the total
      population was retrospectively analyzed for association with mortality. The
      difference in C-reactive protein value between initial and follow-up after 24
      hours (D-CRP) was compared in survivors and non-survivors. The D-CRP, APACHE
      (Acute Physiology and Chronic Health Evaluation) II scoring system and SOFA
      (Sequential Organ Failure Assessment) score were compared by analyzing receiver
      operating characteristic (ROC) curves. RESULTS: Among the 96 subjects, 74
      survived and 22 died. In the total population, age, BUN, creatinine, APACHE II
      and SOFA score, MAP, GCS, hematocrit, respiratory rate, albumin, cholinesterase,
      and the difference in C-reactive protein value between initial and follow-up
      after 24 hours (D-CRP) were found to be associated with mortality. The fatality
      rate of organophosphate poisoning was 22.9% and the D-CRP was found to be
      associated with a significantly higher risk of death in a multiple logistic
      regression (Odds ratio = 1.178, 95% CI = 1.049-1.322, p = 0.006). CONCLUSION: The
      initial serum C-reactive protein and acetylcholinesterase were not found to be
      associated with the severity of acute organophosphate poisoning. However, the
      difference in C-reactive protein value between initial and follow-up after 24
      hours (D-CRP) was associated with mortality in the total population of patients
      with acute organophosphate poisoning.

PMID- 23170820
TI  - Valproate toxicity in a child: two novel observations.

PMID- 23170821
TI  - The beneficial role of vitamin D in human immunodeficiency virus infection.
AB  - Patients with human immuno-deficiency virus (HIV)-infection have a high
      prevalence of abnormal bone metabolism and vitamin D deficiency. Vitamin D
      treatment has some benefit in patients with HIV infection. In this paper, we
      review the evidence for an association between vitamin D and HIV infection.
      Literature search was done from Medline. Genetic studies have provided the
      opportunity to determine which proteins link vitamin D to HIV pathology [i.e.,
      the major histocompatibility complex class II molecules, vitamin D receptor,
      cytochrome P(450), renin-angiotensin system, apoli-poprotein E, liver X receptor,
      toll-like receptor, poly(ADP-ribosyl) polymerase-1, natural resistance-associated
      macrophage protein 1, and the Sp1 promoter gene]. Vitamin D also exerts its
      effect on HIV through nongenomic factors, i.e., ultraviolet radiation exposure,
      matrix metalloproteinase, heme oxygenase-1, the prostaglandins, cyclooxygenase-2,
      and oxidative stress. In conclusion, vitamin D may have a beneficial role in HIV.
      Calcitriol, 1alpha,25-dihydroxyvitamin D3 should be tested in HIV-infected
      population because of its active form of the vitamin D3 metabolite and modulates
      inflammatory cytokine expression. Further investigation with calcitriol in HIV is
      needed.

PMID- 23170822
TI  - Effects of roasting conditions on the changes of stable carbon isotope ratios
      (delta13 C) in sesame oil and usefulness of delta13 c to differentiate blended
      sesame oil from corn oil.
AB  - Differentiating blended sesame oils from authentic sesame oil (SO) is a critical
      step in protecting consumer rights. Stable carbon isotope ratios (delta(13) C),
      color, fluorescence intensity, and fatty acid profiles were analyzed in SO
      prepared from sesame seeds with different roasting conditions and in corn oil
      blended with SO. Sesame seeds were roasted at 175, 200, 225, or 250  degrees C
      for 15 or 30 min at each temperature. SO was mixed with corn oil at varying
      ratios. Roasting conditions ranging from175 to 250  degrees C at the 30 min time
      point did not result in significant changes in delta(13) C (P > 0.05). Values of
      delta(13) C in corn oil and SO from sesame seeds roasted at 250  degrees C for 15
      min were -17.55 and -32.13 0/00, respectively. Fatty acid ratios, including (O +
      L)/(P * Ln) and (L * L)/O, where O, L, P, and Ln were oleic, linoleic, palmitic,
      and linolenic acids, respectively, showed good discriminating abilities among the
      SO blended with corn oil. Therefore, using different combinations of stable
      carbon isotope ratios and some fatty acid ratios can allow successful
      differentiation of authentic SO from SO blended with corn oil.

PMID- 23170823
TI  - Risk factors for acquiring extended-spectrum beta-lactamase-producing
      Enterobacteriaceae in geriatric patients with multiple comorbidities in
      respiratory care wards.
AB  - AIM: Extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae is
      associated with a high mortality rate and increased medical care costs. Elderly
      patients might receive mechanical ventilation with respiratory treatment for the
      long term in respiratory care wards (RCW). This retrospective case-control study
      sought to determine the risk factors for geriatric patients who acquire a urinary
      tract infection with ESBL-producing Escherichia coli or Klebsiella pneumoniae in
      this type of hospital. METHODS: Two RCW participated in this study from September
      2006 to March 2007. Patients suspected of having a UTI were enrolled in this
      study. Urine samples were collected for culture. The medical records and
      demographic data of patients, including days of hospitalization, comorbidities
      and duration of invasive instruments, were recorded. UTI was diagnosed by
      physicians. ESBL-producing isolates were detected using the phenotypic
      confirmatory tests according to the Clinical and Laboratory Standard Institute
      standards. RESULTS: There were 109 patients having 240 sets of clinical data and
      laboratory specimens. The prevalence of ESBL-producing isolates of E. coli. and
      K. pneumoniae were 39.5% and 69.7%, respectively. Patients with multiple
      underlying comorbidities (OR=2.88, P<0.05) or receiving more than two
      antimicrobial agents (OR=3.71, P<0.05) were at an increased risk for acquiring
      the ESBL-producing microorganisms after adjustment for sex, age and days of
      hospitalization. CONCLUSIONS: Geriatric patients with recent exposure to two or
      more antibiotics and two or more numbers of comorbidities were at risk for ESBL
      producing organism infection. Our results suggest that infection control
      procedures in RCW should be concerned with reducing antimicrobial prescriptions
      and patient comorbidities.

PMID- 23170824
TI  - What are the living conditions and health status of those who don't report their
      migration status? A population-based study in Chile.
AB  - BACKGROUND: Undocumented immigrants are likely to be missing from population
      databases, making it impossible to identify an accurate sampling frame in
      migration research. No population-based data has been collected in Chile
      regarding the living conditions and health status of undocumented immigrants.
      However, the CASEN survey (Caracterizacion Socio- Economica Nacional) asked about
      migration status in Chile for the first time in 2006 and provides an opportunity
      to set the base for future analysis of available migration data. We explored the
      living conditions and health of self-reported immigrants and respondents who
      preferred not to report their migration status in this survey. METHODS: Cross
      sectional secondary analysis of CASEN survey in Chile in 2006. OUTCOMES: any
      disability, illness/accident, hospitalization/surgery, cancer/chronic condition
      (all binary variables); and the number of medical/emergency attentions received
      (count variables). Covariates: Demographics (age, sex, marital status,
      urban/rural, ethnicity), socioeconomic status (education level, employment status
      and household income), and material standard of living (overcrowding, sanitation,
      housing quality). Weighted regression models were estimated for each health
      outcome, crude and adjusted by sets of covariates, in STATA 10.0. RESULTS: About
      1% of the total sample reported being immigrants and 0.7% preferred not to report
      their migration status (Migration Status - Missing Values; MS-MV). The MS-MV
      lived in more deprived conditions and reported a higher rate of health problems
      than immigrants. Some gender differences were observed by health status among
      immigrants and the MS-MV but they were not statistically significant. Regressions
      indicated that age, sex, SES and material factors consistently affected MS-MVs'
      chance of presenting poor health and these patterns were different to those found
      among immigrants. Great heterogeneity in both the MS-MV and the immigrants, as
      indicated by wide confidence intervals, prevented the identification of other
      significantly associated covariates. CONCLUSION: This is the first study to look
      at the living conditions and health of those that preferred not to respond their
      migration status in Chile. Respondents that do not report their migration status
      are vulnerable to poor health and may represent undocumented immigrants. Surveys
      that fail to identify these people are likely to misrepresent the experiences of
      immigrants and further quantitative and qualitative research is urgently
      required.

PMID- 23170825
TI  - The attitudes of undergraduate nursing students towards mental health nursing: a
      systematic review.
AB  - AIMS AND OBJECTIVES: To present the findings of a systematic review on (1) the
      attitudes of undergraduate nursing students towards mental health nursing and (2)
      the influence of undergraduate nursing education on the attitudes of
      undergraduate nursing students towards mental health nursing. BACKGROUND:
      Recruitment and retention of mental health nurses is challenging. Undergraduate
      nursing students' attitudes towards mental health nursing may influence whether
      they choose to practice in this specialty upon graduation. DESIGN: A systematic
      review. METHOD: Searches of the CINAHL, MEDLINE and PsycINFO electronic databases
      returned 1400 records, of which 17 met the inclusion criteria for this review. A
      further four papers were obtained through scanning the reference lists of those
      articles included from the initial literature search. RESULTS: Research on the
      attitudes of undergraduate nursing students towards mental health nursing has
      consistently shown that mental health is one of the least preferred areas of
      nursing for a potential career. With respect to the influence of undergraduate
      nursing education on the attitudes of students towards mental health nursing,
      quasi-experimental studies have generally demonstrated that students tended to
      have more favourable attitudes towards mental health nursing when they had
      received more hours of theoretical preparation and undertaken longer clinical
      placements. CONCLUSION: Many nursing students regard mental health nursing as the
      least preferred career option. Education, via classroom teaching and clinical
      placements, seems to engender more positive attitudes towards mental health
      nursing. There is no evidence, however, that changing student attitudes results
      in more graduates beginning careers in mental health nursing. REFERENCE TO
      CLINICAL PRACTICE: The constancy of negative attitudes to mental health nursing
      over time suggests the focus of research should shift. Clinicians have the
      capacity to promote a more positive view of mental health nursing. This requires
      further exploration.

PMID- 23170826
TI  - Transcriptome characterization and gene expression of Epinephelus spp in
      endoplasmic reticulum stress-related pathway during betanodavirus infection in
      vitro.
AB  - BACKGROUND: Grouper (Epinephelus spp) is an economically important fish species
      worldwide. However, viral pathogens such as nervous necrosis virus (NNV) have
      been causing severe infections in the fish, resulting in great loss in the
      grouper aquaculture industry. Yet, the understanding of the molecular mechanisms
      underlying the pathogenicity of NNV is still inadequate, mainly due to
      insufficient genomic information of the host. RESULTS: De novo assembly of
      grouper transcriptome in the grouper kidney (GK) cells was conducted by using
      short read sequencing technology of Solexa/Illumina. A sum of 66,582 unigenes
      with mean length of 603 bp were obtained, and were annotated according to Gene
      Ontology (GO) and Clusters of Orthologous Groups (COG). In addition, the tag
      based digital gene expression (DGE) system was used to investigate the gene
      expression and pathways associated with NNV infection in GK cells. The analysis
      revealed endoplasmic reticulum (ER) stress response was prominently affected in
      NNV-infected GK cells. A further analysis revealed an interaction between the NNV
      capsid protein and the ER chaperone immunoglobulin heavy-chain binding protein
      (BiP). Furthermore, exogenous expression of NNV capsid protein was able to induce
      XBP-1 mRNA splicing in vivo, suggesting a role of the capsid protein in the NNV
      induced ER stress. CONCLUSIONS: Our data presents valuable genetic information
      for Epinephelus spp., which will benefit future study in this non-model but
      economically important species. The DGE profile of ER stress response in NNV
      infected cells provides information of many important components associated with
      the protein processing in ER. Specifically, we showed that the viral capsid
      protein might play an important role in the ER stress response.

PMID- 23170827
TI  - Why restrictions on the immigration of health workers are unjust.
AB  - Some bioethicists and political philosophers argue that rich states should
      restrict the immigration of health workers from poor countries in order to
      prevent harm to people in these countries. In this essay, I argue that
      restrictions on the immigration of health workers are unjust, even if this
      immigration results in bad health outcomes for people in poor countries. I
      contend that negative duties to refrain from interfering with the occupational
      liberties of health workers outweighs rich states' positive duties to prevent
      harm to people in sending countries. Furthermore, I defend this claim against the
      objection that health workers in poor countries acquire special duties to their
      compatriots that render them liable to coercive interference. 

PMID- 23170828
TI  - Advantage of meditation over exercise in reducing cold and flu illness is related
      to improved function and quality of life.
AB  - PURPOSE: To examine whether apparent advantages following training in meditation
      over exercise can be attributed to specific symptoms, functional impairments, or
      quality-of-life indicators assessed by the Wisconsin Upper Respiratory Symptom
      Survey (WURSS-24). METHODS: Results from the randomized controlled trial
      "Meditation or Exercise for Preventing Acute Respiratory Illness" showed mean
      global severity and total days of illness were worse in control (358, 8.9)
      compared with exercise (248, 5.1) or meditation (144, 5.0). Global severity of
      illness was estimated using area under the curve from daily self-reported
      severity scores on the WURSS-24. For this project, we estimated within-group
      WURSS item-level severity and between-group effect sizes (Cohen's "d" statistic)
      relative to control. The item-level effect sizes were grouped into (i) symptom
      and (ii) function and quality of life domains. RESULTS: Among the three groups,
      mediators showed the lowest severity estimates for 21 of 22 WURSS items. Item
      level Cohen's "d" indicated most benefit was evident in WURSS items representing
      function and quality of life. Compared with exercise, meditation fostered larger
      reductions in illness severity, although due mostly to improved function and the
      quality of life domain (d=-0.33, P<0.001) compared with symptom domain (d=-0.22,
      P<0.001). CONCLUSIONS: The apparent advantage of training in meditation over
      exercise for reducing cold and flu illness is explained more by improved function
      and quality of life than by a reduction in symptom severity.

PMID- 23170829
TI  - The development of continuous positive airway pressure: an interview with Dr.
      George Gregory.
AB  - George Gregory, M.D. (1934-), Professor Emeritus at the University of California,
      San Francisco, has made numerous contributions to neonatology and pediatric
      anesthesia through his research efforts and authoritative textbook, Gregory's
      Pediatric Anesthesia. However he identified his defining moment as the occasion
      he saved the life of an infant suffering from neonatal respiratory distress
      syndrome by using continuous positive airway pressure (CPAP) ventilation. The
      development of CPAP by Gregory revolutionized the treatment of premature infants
      with respiratory failure. Prior to the creation of this treatment, the mortality
      rate of neonates with respiratory distress syndrome was >50%. The innovation
      markedly improved the ventilation of infants with respiratory distress and led to
      significant improvements in survival rates. Based on an interview with Dr.
      Gregory, this article describes the discovery of CPAP and reviews his career in
      advancing pediatric anesthesia and critical care medicine.

PMID- 23170830
TI  - A sense of home in residential care.
AB  - Moving into a residential care facility requires a great deal of adjustment to an
      environment and lifestyle entirely different from that of one's previous life.
      Attachment to place is believed to help create a sense of home and maintain self
      identity, supporting successful adjustment to contingencies of ageing. The
      purpose of this study was to deepen our understanding of processes and strategies
      by which older people create a sense of home in residential care. Our findings
      show that a sense of home in residential care involves strategies related to
      three dimensions of the environment - attachment to place, to space and
      attachment beyond the institution - and that the circumstances under which older
      people manage or fail in creating attachment, consist of psychosocial processes
      involving both individual and shared attitudes and beliefs. Assuming that
      attachment is important to human existence regardless of age, attention must be
      paid to optimize the circumstances under which attachment is created in
      residential care, and how nursing interventions can help speed up this process
      due to the frail and vulnerable state of most older residents. 

PMID- 23170832
TI  - Reduced and oxidized forms of the Pt-organometallic version of polyaniline.
AB  - This work represents an effort to synthesize all four forms of polyaniline (PANI)
      in its organometallic versions. Polymers containing substituted 1,4-benzoquinone
      diimine or 1,4-diaminobenzene units in the backbone exhibiting the general
      structure (C=CC(6)H(4)-N?C(6)X(4)?N-C(6)H(4)C=C-PtL(2))(n) and (C=CC(6)H(4)NH
      C(6)X(4)-NHC(6)H(4)C=C-PtL(2))(n) along with the corresponding model compounds
      (C=CC(6)H(4)-N?C(6)X(4)?N-C(6)H(4)C=C)(PtL(2)Cl)(2) and (C=CC(6)H(4)NH-C(6)X(4)
      NHC(6)H(4)C=C)(PtL(2)Cl)(2) (L = PBu(3); X = H, F, Cl) were synthesized. The
      polymers and corresponding model compounds were characterized (including (1)H and
      (31)P NMR, IR, mass spectra, elemental analysis, and X-ray structure
      determinations) and investigated for their redox properties in the absence and in
      the presence of acid. Their optical properties, including ns transient
      spectroscopy were also investigated. These properties were interpreted through
      density functional theory (DFT) and time-dependent DFT (TDDFT) computations.
      These materials are found to be oligomers (GPC) with thermal stability (TGA)
      reaching 350  degrees C. The greatest stabilities were found in the cases with X
      = F. Using a data bank of 8 X-ray structures of diimine derivatives, a
      relationship between the C?N bond distance and the dihedral angle between the
      benzoquinone ring and the flanking phenyl planes is noted. As the size of the
      substituent X on the benzoquinone center increases, the degree of conjugation
      decreases as demonstrated by the C?N bond length. The largest dihedral angles are
      noted for X = Cl. These polymers exhibit drastic chemical differences when X is
      varied (X = H, F, Cl). The completely reduced polymer (C=CC(6)H(4)NH-C(6)H(4)
      NHC(6)H(4)C=C-PtL(2))(n) (i.e., X = H) was not chemically accessible whereas in
      the cases of X = F, Cl, these materials were obtained and represent the first
      examples of fully reduced organometallic versions of PANI (i.e.,
      leucoemaraldine). For the (C=CC(6)H(4)-N?C(6)X(4)?N-C(6)H(4)C=C-PtL(2))(n)
      polymers, the completely oxidized form for X = H was isolated (pernigraniline),
      but for X = F and Cl, only the largely reduced mixed-valence form (i.e.,
      emaraldine) was obtained via chemical routes. In acidic solutions, the chemically
      accessible polymer for X = H, (C=CC(6)H(4)-N?C(6)H(4)?N-C(6)H(4)C=C-PtL(2))(n),
      exhibits two chemically reversible waves indicating that the reduced form
      (C=CC(6)H(4)NH-C(6)H(4)-NHC(6)H(4)C=C-PtL(2))(n) can be generated. The absorption
      spectra of the highly colored diimine-containing species exhibit a broad charge
      transfer band (assigned based on DFT calculations (B3LYP); C(6)H(4)C=C-PtL(2)
      C=CC(6)H(4) -> N?C(6)X(4)?N) in the 450-800 nm window red shifting according X =
      H -> Cl -> F, consistent with their relative inductive effect. The largest
      absorptivity is measured for X = H because this polymer is fully oxidized whereas
      for the cases where X = F and Cl, these polymers exists in the mixed valence
      form. The ns transient absorption spectra of two polymers (X = F; reduced and
      mixed-valence polymers) were measured. The triplet excited state in the mixed
      valence polymer is dominated by the reduced diamine residue and the T(1)-T(n)
      absorption of the diimine is entirely quenched.

PMID- 23170831
TI  - Potential association between TLR4 and chitinase 3-like 1 (CHI3L1/YKL-40)
      signaling on colonic epithelial cells in inflammatory bowel disease and colitis
      associated cancer.
AB  - Inflammatory bowel disease (IBD) is a group of inflammatory disorders in the
      small and large intestines. Several studies have proved that persistent and
      disregulated host/microbial interactions are required for the development of IBD.
      It is well known that chronic IBD is strongly associated with an increased risk
      of developing colorectal cancer by 0.5-1% annually, 8-10 years after the initial
      diagnosis. To detect the tiny dysplasia or early stage of cancer in chronic IBD
      patients, a tremendous amount of effort is currently directed for improving
      colonoscopic technology and noninvasive serological marker development. However,
      there is only a limited amount of data available to understand the exact
      mechanism of how long term chronic colitis is connected to the development of
      colorectal tumors. Recently, our group has identified significantly increased
      expression of chitinase 3-like 1 (CHI3L1) molecule in non-dysplastic mucosa from
      patients with IBD and remote dysplasia/cancer, compared to patients with IBD
      without dysplasia or healthy controls. CHI3L1 seems to contribute to the
      proliferation, migration, and neoplastic progression of colonic epithelial cells
      (CECs) under inflammatory conditions. Furthermore, the TLR4-mediated
      intracellular signaling cascade is likely to interact with CHI3L1 signaling in
      CECs. In this review article, we have concisely summarized the cellular and
      molecular mechanisms underlining the development of IBD and colitis-associated
      cancer, with particular focus on the TLR4- and CHI3L1-signaling pathways in CECs.

PMID- 23170833
TI  - SDF-1alpha upregulation by atorvastatin in rats with acute myocardial infarction
      via nitric oxide production confers anti-inflammatory and anti-apoptotic effects.
AB  - BACKGROUND: The effects of atorvastatin on SDF-1alpha expression under acute
      myocardial infarction (AMI) are still unclear. Therefore, our present study is to
      investigate the roles and mechanisms of atorvastatin treatment on SDF-1alpha
      expression in rats with AMI. METHODS: Male Sprague-Dawley rats were underwent
      permanent coronary artery ligation and randomly assigned into four groups as
      follow: blank control (B), atorvastatin (A), atorvastatin plus L-NAME (A+L-NAME),
      and atorvastatin plus AMD3100 (A+AMD3100). Rats underwent similar procedure but
      without ligation were used as group sham operated (S). Atorvastatin (10mg/Kg/d
      body weight) was administrated by gavage to rats in three atorvastatin treated
      groups, and L-NAME (40 mg/Kg/d body weight) or AMD3100 (5mg/Kg/d body weight) was
      given to group A+L-NAME or A+AMD3100, respectively. RESULTS: Comparing with group
      B, NO production, SDF-1alpha and CXCR4 expression were significantly up-regulated
      in three atorvastatin treated groups at the seventh day. However, the increments
      of SDF-1alpha and CXCR4 expression in group A+L-NAME were reduced when NO
      production was inhibited by L-NAME. Anti-inflammatory and anti-apoptotic effects
      of atorvastatin were offset either by decrease of SDF-1alpha and CXCR4 expression
      (by L-NAME) or blockage of SDF-1alpha coupling with CXCR4 (by AMD3100).
      Expression of STAT3, a cardioprotective factor mediating SDF-1alpha/CXCR4 axis
      induced cardiac protection, was up-regulated most significantly in group A. The
      effects of atorvastatin therapy on cardiac function were also abrogated either
      when SDF-1alpha and CXCR4 expression was diminished or the coupling of SDF-1alpha
      with CXCR4 was blocked. CONCLUSION: SDF-1alpha upregulation by atorvastatin in
      rats with AMI was, at least partially, via the eNOS/NO dependent pathway, and SDF
      1alpha upregulation and SDF-1alpha coupling with CXCR4 conferred anti
      inflammatory and anti-apoptotic effects under AMI setting which we speculated
      that ultimately contributed to cardiac function improvement.

PMID- 23170834
TI  - Notoginsenoside R1 attenuates cardiac dysfunction in endotoxemic mice: an insight
      into oestrogen receptor activation and PI3K/Akt signalling.
AB  - BACKGROUND AND PURPOSE: Notoginsenoside R1 (NG-R1), a novel phytoestrogen
      isolated from Panax notoginseng, is believed to have anti-inflammatory, anti
      oxidative and anti-apoptotic properties. However, its cardioprotective properties
      and underlying mechanisms are largely unknown. Here we have assessed the
      contribution of the anti-inflammatory effects of NG-R1 to the amelioration of
      septic cardiac dysfunction and inflammation in mice. EXPERIMENTAL APPROACH: We
      assessed cardiac function in mice by echocardiography. We studied the protein or
      mRNA levels of some inflammatory factors, apoptotic factors and oestrogen
      receptors (ERs) in heart tissues upon stimulation with bacterial LPS, NG-R1 or
      some pharmacological inhibitors. KEY RESULTS: Six hours after LPS administration
      (10 mg.kg(-1) , i.p.) cardiac function was decreased, an effect attenuated by NG
      R1 pretreatment (25 mg.kg(-1) .d(-1) , i.p.). NG-R1 also improved the imbalance
      between iNOS and eNOS, prevented activation of NF-kappaB and the subsequent
      myocardial inflammatory and apoptotic responses in endotoxemic mice. The effects
      of NG-R1 were closely associated with activation of the oestrogen receptor
      ERalpha and of PI3K/PKB (Akt) signalling, as characterized by NG-R1-induced
      preservation in ERalpha, phospho-Akt, phospho-GSK3beta and I-kappaBalpha, and of
      cardiac function that was partially blocked by selective inhibitors of ERalpha or
      PI3K. However, NG-R1 had no effect on LPS-activated TLR-4. CONCLUSIONS AND
      IMPLICATIONS: NG-R1 is a promising compound for protecting the heart from septic
      shock, possibly via the activation of ERalpha and PI3K/Akt signalling. This
      mechanism produces blockade of NF-kappaB activation and attenuation of the pro
      inflammatory state and apoptotic stress in the myocardium.

PMID- 23170835
TI  - Molecular mechanisms of selective estrogen receptor modulator activity in human
      breast cancer cells: identification of novel nuclear cofactors of antiestrogen
      ERalpha complexes by interaction proteomics.
AB  - Estrogen receptor alpha (ERalpha) is a ligand-activated transcription factor that
      controls key cellular pathways via protein-protein interactions involving
      multiple components of transcriptional coregulator and signal transduction
      complexes. Natural and synthetic ERalpha ligands are classified as agonists
      (17beta-estradiol/E(2)), selective estrogen receptor modulators (SERMs:
      Tamoxifen/Tam and Raloxifene/Ral), and pure antagonists (ICI 182,780
      Fulvestrant/ICI), according to the response they elicit in hormone-responsive
      cells. Crystallographic analyses reveal ligand-dependent ERalpha conformations,
      characterized by specific surface docking sites for functional protein-protein
      interactions, whose identification is needed to understand antiestrogen effects
      on estrogen target tissues, in particular breast cancer (BC). Tandem affinity
      purification (TAP) coupled to mass spectrometry was applied here to map nuclear
      ERalpha interactomes dependent upon different classes of ligands in hormone
      responsive BC cells. Comparative analyses of agonist (E(2))- vs antagonist (Tam,
      Ral or ICI)-bound ERalpha interacting proteins reveal significant differences
      among ER ligands that relate with their biological activity, identifying novel
      functional partners of antiestrogen-ERalpha complexes in human BC cell nuclei. In
      particular, the E(2)-dependent nuclear ERalpha interactome is different and more
      complex than those elicited by Tam, Ral, or ICI, which, in turn, are
      significantly divergent from each other, a result that provides clues to explain
      the pharmacological specificities of these compounds.

PMID- 23170836
TI  - Physical-mechanical properties of agar/kappa-carrageenan blend film and derived
      clay nanocomposite film.
AB  - Binary blend films with different mixing ratio of agar and kappa-carrageenan were
      prepared using a solution casting method with and without nanoclay and the effect
      of their composition on the mechanical, water vapor barrier, and water resistance
      properties was tested. The tensile strength (TS) of the kappa-carrageenan film
      was greater than that of agar film. The water vapor permeability (WVP) of the
      agar film was lower than that of kappa-carrageenan film, the swelling ratio (SR)
      and water solubility (WS) of kappa-carrageenan film were higher than those of
      agar film. Each property of the binary blend films varied proportionately
      depending on the mixing ratio of each component. The XRD result indicated that
      the nanocomposite with agar/kappa-carrageenan/clay (Cloisite((r)) Na(+)) was
      intercalated. Consequently, the mechanical strength, water vapor barrier
      properties, and water contact angle (CA) were significantly (P < 0.05) improved
      through nanocomposite formation.

PMID- 23170837
TI  - Posaconazole after previous antifungal therapy with voriconazole for therapy of
      invasive aspergillus disease, a retrospective analysis.
AB  - Invasive aspergillosis is an important cause of morbidity and mortality in
      haematological patients. Current guidelines recommend voriconazole as first-line
      therapy. A change in class of antifungal agent is generally recommended for
      salvage therapy. The focus of this analysis was to assess if posaconazole is
      suitable for salvage therapy following voriconazole treatment. This was a
      retrospective investigation on patients with sequential antifungal therapy of
      posaconazole after voriconazole identified at four German hospitals. Response
      rates at 30 and 60 days following start of posaconazole application and toxicity
      of azoles by comparing liver enzymes and cholestasis parameters were evaluated.
      Data were analysed by descriptive statistics. Overall, the success rate was 72.2%
      [15 of 36 patients showed complete response (41.7%), 11 patients partial response
      (30.6%) at any time point], eight patients failed treatment and two were not
      evaluable. Mean laboratory values increased during voriconazole and decreased
      during posaconazole treatment: aspartate aminotransferase (increase: 31.9 U l(-1)
      vs. decrease: 19.6 U l(-1) ), alanine aminotransferase (32.4 U l(-1) vs. 19.8 U
      l(-1) ), gamma-glutamyl transferase (124.2 U l(-1) vs. 152.3 U l(-1) ) and
      alkaline phosphatase (71.5 U l(-1) vs. 40.3 U l(-1) ) respectively. No patient
      discontinued posaconazole therapy due to an adverse event. In this analysis
      posaconazole was a safe and effective antifungal salvage therapy in patients with
      prior administration of another triazole.

PMID- 23170839
TI  - Recognition of categorised words: repetition effects in rote study.
AB  - In the recognition-memory mirror effect one stimulus class exhibits both more
      hits and fewer false alarms than a contrasting class. This outcome is frequently
      detected when strong (e.g., repeated, long-duration study) and weak items have
      appeared in different lists but less so within lists. The mirror effect may
      reflect people's assignment of a more lenient recognition criterion to the weak
      than the strong class. The present study asked whether a paradigm that has
      yielded within-list mirror effects when participants make gist ratings during
      study (Singer, 2009, 2011) likewise obtains in rote study. In Experiments 1 and 2
      people studied words from category pairs such that the stimuli from one category
      only were repeated three times. Both hits and false alarms were consistently
      higher for the repeated than the unrepeated condition, a pattern labelled
      "concordant" (rather than mirror). This might reflect the either a positive
      "distribution shift" of the repeated-category lures or a metacognitive strategy.
      Experiment 3 coupled the same study procedure with two-alternative forced-choice
      testing (2AFC) to deny the distribution shift explanation. The sorts of strategy
      that might favour repeated over unrepeated lures are considered.

PMID- 23170838
TI  - Measuring the accuracy of self-reported height and weight in a community-based
      sample of young people.
AB  - BACKGROUND: Self-reported anthropometric data are commonly used to estimate
      prevalence of obesity in population and community-based studies. We aim to: 1)
      Determine whether survey participants are able and willing to self-report height
      and weight; 2) Assess the accuracy of self-reported compared to measured
      anthropometric data in a community-based sample of young people. METHODS:
      Participants (16-29 years) of a behaviour survey, recruited at a Melbourne music
      festival (January 2011), were asked to self-report height and weight; researchers
      independently weighed and measured a sub-sample. Body Mass Index was calculated
      and overweight/obesity classified as >=25 kg/m2. Differences between measured and
      self-reported values were assessed using paired t-test/Wilcoxon signed ranks
      test. Accurate report of height and weight were defined as <2 cm and <2 kg
      difference between self-report and measured values, respectively. Agreement
      between classification of overweight/obesity by self-report and measured values
      was assessed using McNemar's test. RESULTS: Of 1405 survey participants, 82% of
      males and 72% of females self-reported their height and weight. Among 67
      participants who were also independently measured, self-reported height and
      weight were significantly less than measured height (p=0.01) and weight (p<0.01)
      among females, but no differences were detected among males. Overall, 52%
      accurately self-reported height, 30% under-reported, and 18% over-reported; 34%
      accurately self-reported weight, 52% under-reported and 13% over-reported. More
      females (70%) than males (35%) under-reported weight (p=0.01). Prevalence of
      overweight/obesity was 33% based on self-report data and 39% based on measured
      data (p=0.16). CONCLUSIONS: Self-reported measurements may underestimate weight
      but accurately identified overweight/obesity in the majority of this sample of
      young people.

PMID- 23170840
TI  - The prevalence and correlates of alcohol use disorder amongst bipolar patients in
      a hospital setting, Malaysia.
AB  - OBJECTIVE: To determine the prevalence of alcohol-use disorder and associated
      correlates amongst bipolar patients in a university hospital in Malaysia.
      METHODS: In this cross-sectional study, a total of 121 bipolar disorder patients
      were included. Their alcohol use disorders were assessed with the Mini
      International Neuropsychiatric Interview (plus version) and the Addiction
      Severity Index-Lite-Clinical Factors version. The number of lifetime
      hospitalizations and the survival days (the number of days between the last
      discharge and the most current readmission) were calculated. RESULTS: The
      prevalence of alcohol-use disorder amongst bipolar patients was 18.2%. Indian
      ethnicity was the only demographic factor that was statistically associated with
      alcohol-use disorder (p < 0.03). Those with alcohol-use disorder had a
      significantly higher rate of suicidal attempt (p < 0.01) and more psychiatric
      hospitalizations than those without after adjusting for gender, race, employment
      status, education level and duration of illness (p < 0.01). CONCLUSIONS: The
      prevalence of alcohol-use disorder was low in bipolar patients but highin the
      general population of Malaysia. Since alcohol-use disorder, as well as the
      potential interactions with the course of the disorder, is highly prevalent
      amongst bipolar patients, alcohol use should be addressed in these patients.

PMID- 23170841
TI  - Dehydrogenative amide synthesis: azide as a nitrogen source.
AB  - A new atom-economical strategy to amide linkage from an azide and alcohol
      liberating hydrogen and nitrogen was developed with an in situ generated
      ruthenium catalytic system. The reaction has broad substrate generality including
      diols for the synthesis of cyclic imides.

PMID- 23170842
TI  - The application of Chinese medicine to novel drug discovery.
AB  - INTRODUCTION: The apparent productivity crisis in the pharmaceutical industry and
      the economic and political rise of China have contributed to renewed interest in
      the application of Chinese medicine for drug discovery. AREAS COVERED: The author
      presents an overview of the historical development and basic principles of theory
      and practice of Chinese herbal medicine, its materia medica and prescription
      formulas, and discusses the motivation for and rationale of its application to
      drug discovery. Furthermore, the author distinguishes the five main approaches to
      drug discovery from Chinese herbal medicine, based on the decreasing amount and
      detail of historical and clinical Chinese medicine knowledge that informed the
      research effort. EXPERT OPINION: Many compounds that have been isolated from the
      Chinese materia medica exhibit pharmacological activities comparable to
      pharmaceutical drugs. With the exception of the antimalarial drug artemisinin,
      however, this knowledge has not led to the successful development of new drugs
      outside of China. The chance of success in a Chinese medicine-based drug
      discovery effort will be increased by consideration of the empirical knowledge
      that has been documented over many centuries in the historical materia medica and
      prescription literature. Most Chinese medicine-derived compounds affect more than
      one target and do not correspond to the one compound/one-target drug discovery
      paradigm. A new frontier is opening up with the development of drugs consisting
      of combinations of multiple compounds acting on multiple targets under the
      paradigm of network pharmacology. The ancient practice of combining multiple
      drugs in prescription formulas can serve as inspirational analogy and a practical
      guide.

PMID- 23170843
TI  - A systematic review of interventions to enhance access to best practice primary
      health care for chronic disease management, prevention and episodic care.
AB  - BACKGROUND: Although primary health care (PHC) is a key component of all health
      care systems, services are not always readily available, accessible or
      affordable. This systematic review examines effective strategies to enhance
      access to best practice processes of PHC in three domains: chronic disease
      management, prevention and episodic care. METHODS: An extensive search of
      bibliographic data bases to identify peer and non-peer reviewed literature was
      undertaken. Identified papers were screened to identify and classify intervention
      studies that measured the impact of strategies (singly or in combination) on
      change in use or the reach of services in defined population groups (evaluated
      interventions). RESULTS: The search identified 3,148 citations of which 121 were
      intervention studies and 75 were evaluated interventions. Evaluated interventions
      were found in all three domains: prevention (n = 45), episodic care (n = 19), and
      chronic disease management (n = 11). They were undertaken in a number of
      countries including Australia (n = 25), USA (n = 25), and UK (n = 15). Study
      quality was ranked as high (31% of studies), medium (61%) and low (8%). The 75
      evaluated interventions tested a range of strategies either singly (n = 46
      studies) or as a combination of two (n = 20) or more strategies (n = 9).
      Strategies targeted both health providers and patients and were categorised to
      five groups: practice re-organisation (n = 43 studies), patient support (n = 29),
      provision of new services (n = 19), workforce development (n = 11), and financial
      incentives (n = 9). Strategies varied by domain, reflecting the complexity of
      care needs and processes. Of the 75 evaluated interventions, 55 reported positive
      findings with interventions using a combination of strategies more likely to
      report positive results. CONCLUSIONS: This review suggests that multiple, linked
      strategies targeting different levels of the health care system are most likely
      to improve access to best practice PHC. The proposed changes in the structure of
      PHC in Australia may provide opportunities to investigate the factors that
      influence access to best practice PHC and to develop and implement effective,
      evidence based strategies to address these.

PMID- 23170844
TI  - Association of serum uric acid level with muscle strength and cognitive function
      among Chinese aged 50-74 years.
AB  - AIM: Previous studies have shown that uric acid (UA) has strong anti-oxidant
      properties, and that high circulating levels of UA are prospectively associated
      with improved muscle function and cognitive performances in elderly Caucasians.
      We carried out a replication study in elderly Chinese using cross-sectional
      design. METHODS: Data from 2006 individuals aged 50-74 years who participated in
      a population-based cross-sectional survey in Qingdao, China, were analyzed. Hand
      grip strength was measured in kilograms by using an electronic dynamometer. The
      sit-to-stand (STS) test time was used to represent lower limb strength. The Mini
      Mental State Examination (MMSE) was used to estimate the participants' cognitive
      function. Lifestyle, comorbidities and laboratory measures were considered as
      potential confounders. Multiple linear regression models and binary logistic
      regression were fitted to find the association of UA with strength measures and
      cognitive performances. RESULTS: Participants were grouped according to UA
      tertiles (<257.75 mmol/L, >= 257.75 and <= 359.00 mmol/L, >359.00 mmol/L). Hand
      grip strength significantly increased across UA tertiles (26.4 +/- 8.5 kg; 30.1
      +/- 10.5 kg; 35.0 +/- 11.4 kg; P<0.001), and prevalence of cognitive disorder
      declined across UA tertiles (7.9%, 4.9%, 3.1%; P=0.012). After adjusting for
      potential confounders, high UA level remained significantly associated with high
      grip strength (P=0.023) and decreased risk of cognitive disorder with an OR of
      1.002 (95% CI 1.000-1.004; P=0.022). However, UA level was not significantly
      associated with STS time (P=0.780). CONCLUSIONS: Our findings suggested that
      notwithstanding the associated increased risk of cardiovascular disease, UA might
      play a protective role in aging-associated decline in muscle strength and
      cognitive function.

PMID- 23170845
TI  - Chronic venous ulceration of leg associated with peripheral arterial disease: an
      underappreciated entity in developing country.
AB  - Chronic venous ulcer can often be associated with asymptomatic peripheral
      arterial disease (PAD), which usually remains undiagnosed adding significantly to
      the morbidity of these patients. The Ankle-Brachial Pressure Index (ABPI) is
      suggested for PAD evaluation. Many PAD studies were conducted in western
      countries, but there is a scarcity of data on the prevalence of PAD in clinical
      venous ulcer patient in developing countries. We conducted a study in a tertiary
      care hospital of eastern part of India to find out the prevalence of PAD in
      venous ulcer patients, and also to find the sensitivity of ABPI as a diagnostic
      tool in these patients. We evaluated clinically diagnosed patients with venous
      ulcer using ABPI and Colour Doppler study for the presence of PAD. Possible
      associations such as age, sex, body mass index (BMI), smoking, hypertension and
      atherosclerosis were studied. All results were analysed using the software
      Statistica version 6. PAD was present in 23 (27.71%) patients. Older age, longer
      duration, smoking, high BMI and hypertension were found to be significantly
      associated with PAD. A very strong level of agreement was found between venous
      Doppler and ABPI. Assessment for the presence of PAD is important in all
      clinically diagnosed venous ulcer patients. ABPI being a simple, non-invasive
      outpatient department (OPD)-based procedure, can be routinely used in cases of
      venous ulcer to find out the hidden cases of PAD even in developing countries. 

PMID- 23170847
TI  - Increased production of hydrogen peroxide by peripheral blood monocytes
      associated with smoking exposure intensity in smokers.
AB  - BACKGROUND: Smoking is known to be associated with oxidative stress; however, it
      has not been elucidated whether the oxidative response is influenced by the
      intensity of smoking exposure. OBJECTIVES: Evaluate the effect of smoking
      exposure on the secretion of hydrogen peroxide (H2O2) by the peripheral blood
      monocytes of smokers. METHODS: A total of 25 smokers (50.3+/-8.8 years, 48% male)
      underwent the following evaluations: spirometry, pulse oximetry, body composition
      and total peripheral blood count. Peripheral blood monocyte (PBM) cultures were
      isolated and maintained, and IL-6 and TNF-alpha were measured in the plasma and
      in the supernatants of spontaneous and stimulated cultures. H2O2 was evaluated in
      the supernatants of the PBM cultures, and a subset of the PBM culture
      supernatants was stimulated with phorbol myristate acetate (PMA). We also
      evaluated 38 healthy controls (49.1+/-8.2 years, 42% male). RESULTS: The
      spontaneous and stimulated monocytes' secretion of H2O2 were statistically higher
      in the smokers than in the healthy controls (p<0.001). The H2O2 secretions were
      statistically significant higher after stimulation with PMA in both groups
      (p<0.001). In the multiple regression analysis, we identified a positive,
      statistically significant association between pack-years of smoking and the
      spontaneous secretion of H2O2 by PBM culture, adjusted for potential confounding
      variables. The association between PBM culture secretion of H2O2 and the
      production of TNF-alpha and IL-6 was not significant. CONCLUSION: We identified a
      positive association between higher production of H2O2 in smokers and higher
      smoking exposure during life. The influence of pack-years smoking may be a key
      modifiable factor in oxidative stress associated to smoking.

PMID- 23170846
TI  - Genomic resources for a model in adaptation and speciation research:
      characterization of the Poecilia mexicana transcriptome.
AB  - BACKGROUND: Elucidating the genomic basis of adaptation and speciation is a major
      challenge in natural systems with large quantities of environmental and
      phenotypic data, mostly because of the scarcity of genomic resources for non
      model organisms. The Atlantic molly (Poecilia mexicana, Poeciliidae) is a small
      livebearing fish that has been extensively studied for evolutionary ecology
      research, particularly because this species has repeatedly colonized extreme
      environments in the form of caves and toxic hydrogen sulfide containing springs.
      In such extreme environments, populations show strong patterns of adaptive trait
      divergence and the emergence of reproductive isolation. Here, we used RNA
      sequencing to assemble and annotate the first transcriptome of P. mexicana to
      facilitate ecological genomics studies in the future and aid the identification
      of genes underlying adaptation and speciation in the system. DESCRIPTION: We
      provide the first annotated reference transcriptome of P. mexicana. Our
      transcriptome shows high congruence with other published fish transcriptomes,
      including that of the guppy, medaka, zebrafish, and stickleback. Transcriptome
      annotation uncovered the presence of candidate genes relevant in the study of
      adaptation to extreme environments. We describe general and oxidative stress
      response genes as well as genes involved in pathways induced by hypoxia or
      involved in sulfide metabolism. To facilitate future comparative analyses, we
      also conducted quantitative comparisons between P. mexicana from different river
      drainages. 106,524 single nucleotide polymorphisms were detected in our dataset,
      including potential markers that are putatively fixed across drainages.
      Furthermore, specimens from different drainages exhibited some consistent
      differences in gene regulation. CONCLUSIONS: Our study provides a valuable
      genomic resource to study the molecular underpinnings of adaptation to extreme
      environments in replicated sulfide spring and cave environments. In addition,
      this study adds to the increasing number of genomic resources in the family
      Poeciliidae, which are widely used in comparative analyses of behavior, ecology,
      evolution, and medical genetics.

PMID- 23170848
TI  - Promoting fruit and vegetable consumption: the role of message framing and
      autonomy.
AB  - OBJECTIVE: Previous studies have shown that gain-framed messages (vs. loss-framed
      messages) are more effective when advocating 'low-risk' prevention behaviours
      (e.g., diet, exercise, dental flossing) that minimize the risk of a health
      problem.The objective of the reported research was to explore whether autonomy
      moderated the effectiveness of gain-framed vs. loss-framed messages encouraging
      fruit and vegetable consumption. DESIGN: A prospective design was used for this
      study. METHOD: At time 1, participants (N = 177) completed a measure of autonomy
      and read either a gain-framed message (describing the benefits of fruit and
      vegetable consumption) or a loss-framed message (describing the disadvantages of
      not eating fruit and vegetables). At time 2, participants reported their fruit
      and vegetable consumption over the preceding 7 days. RESULTS: Autonomy moderated
      the effect of message framing. Gain-framed messages only prompted fruit and
      vegetable consumption amongst those with high levels of autonomy. CONCLUSION: The
      study identifies a key role for autonomy in shaping recipients' responses to
      framed messages promoting fruit and vegetable consumption.

PMID- 23170849
TI  - Adherence to treatment among adolescents in a psychiatric ward.
AB  - AIMS AND OBJECTIVES: To examine the adolescent's adherence in psychiatric
      inpatient care that includes both medication and non-pharmacological treatment.
      BACKGROUND: Adolescents can deny having a problem or being in need of treatment
      and are therefore prone to defying attempts to engage them in a collaborative
      treatment process. There is still little information in the literature concerning
      adherence to psychiatric inpatient treatment among mentally ill adolescents,
      especially focusing on the entire treatment period and all forms of treatment.
      DESIGN: This is a retrospective, mixed-method study. METHODS: Data were collected
      from discharge reports written by doctors (n = 72) and were subjected to
      inductive content analysis. Adherence to all forms of treatment was considered,
      over the entirety of the treatment period rather than focusing on a single
      specific time point. RESULTS: Three main adherence-related content categories
      were identified: non-adherence to treatment, adherence to treatment and
      challenges of adherence. The last of these categories contains information on
      factors that affect adolescent treatment adherence. CONCLUSIONS: We found that
      adherent adolescents are cooperative, willing to receive treatment and
      participate actively in therapies aimed at relieving their mental symptoms or
      illness. RELEVANCE TO CLINICAL PRACTICE: The findings presented herein are likely
      to be informative in the context of inpatient treatment, and it is expected that
      the results presented herein will help to improve adolescents' quality of
      treatment.

PMID- 23170850
TI  - Aberrant expression of CD133 in non-small cell lung cancer and its relationship
      to vasculogenic mimicry.
AB  - BACKGROUND: To investigate on expressions and clinical significances of CD133
      protein and vasculogenic mimicry (VM) in primary non-small cell lung cancer
      (NSCLC). METHODS: The specimens of NSCLC from 305 Chinese patients with follow-up
      were analyzed for CD133 protein expression and VM by immunohistochemical and
      histochemical staining. RESULTS: In NSCLC, positive rates of 48.9% and 35.7% were
      obtained for CD133 and VM, respectively. The VM and expression of CD133 were
      significantly higher in carcinoma than in normal. There were a positive
      relationship between the VM and expression of CD133 and the tumor grade, lymph
      node metastasis and clinical stage (all P<0.05). The overall mean survival time
      of the patients with CD133 and VM positive expression was lower than that of
      patients with negative expression. Microvessel density (MVD) was positive
      corresponded with the grade, lymph node metastasis and clinical stage (all
      P<0.05). The overall mean survival time of the patients with MVD>=22's group was
      shorter than that of patients with MVD<22's group. Pathological-tumor-node
      metastasis (pTNM) stage, positive expression of CD133 and VM, postoperative
      therapy and MVD were independent prognostic factors of NSCLC (P<0.05).
      Immunohistochemistry revealed an important intratumoral heterogeneity in all four
      CD133 expression profiles. CONCLUSIONS: VM, MVD and expression of CD133 are
      related to differentiation, lymph node metastasis, clinical stage, and prognosis.
      It is suggested that CD133, VM and MVD should be considered as a potential marker
      for the prognosis.

PMID- 23170851
TI  - Guidance for contact tracing of cases of Lassa fever, Ebola or Marburg
      haemorrhagic fever on an airplane: results of a European expert consultation.
AB  - BACKGROUND: Travel from countries where viral haemorrhagic fevers (VHF) are
      endemic has increased significantly over the past decades. In several reported
      VHF events on airplanes, passenger trace back was initiated but the scale of the
      trace back differed considerably. The absence of guidance documents to help the
      decision on necessity and scale of the trace back contributed to this
      variation.This article outlines the recommendations of an expert panel on Lassa
      fever, Ebola and Marburg haemorrhagic fever to the wider scientific community in
      order to advise the relevant stakeholders in the decision and scale of a possible
      passenger trace back. METHOD: The evidence was collected through review of
      published literature and through the views of an expert panel. The guidance was
      agreed by consensus. RESULTS: Only a few events of VHF cases during air travel
      are reported in literature, with no documented infection in followed up contacts,
      so that no evidence of transmission of VHF during air travel exists to date.
      Based on this and the expert opinion, it was recommended that passenger trace
      back was undertaken only if: the index case had symptoms during the flight; the
      flight was within 21 days after detection of the event; and for Lassa fever if
      exposure of body fluid has been reported. The trace back should only be done
      after confirmation of the index case. Passengers and crew with direct contact,
      seat neighbours (+/- 1 seat), crew and cleaning personal of the section of the
      index case should be included in the trace back. CONCLUSION: No evidence has been
      found for the transmission of VHF in airplanes. This information should be taken
      into account, when a trace back decision has to be taken, because such a measure
      produces an enormous work load. The procedure suggested by the expert group can
      guide decisions made in future events, where a patient with suspected VHF
      infection travelled on a plane. However, the actual decision on start and scale
      of a trace back always lies in the hands of the responsible people taking all
      relevant information into account.

PMID- 23170852
TI  - Pain perception in schizophrenia: evidence of a specific pain response profile.
AB  - OBJECTIVE: Ever since the characterization of schizophrenia, clinicians have
      noted abnormal pain sensitivity in their patients. The published literature,
      however, is inconsistent concerning the nature of the change reported. The
      objective of this study was to characterize the pain response profile of
      schizophrenic patients by providing both acute and prolonged (i.e., rapidly
      repeating) painful stimuli to schizophrenic participants and control subjects.
      PARTICIPANTS: Twelve schizophrenic subjects and eleven controls were included in
      the final analysis. Diagnosis was made according to Diagnostic and Statistical
      Manual of mental disorders-4th edition, text revision (DSM-IV-TR) criteria.
      METHODS: Intermittent, transcutaneous stimulations of the left sural nerve were
      administered to all participants. Painful sural nerve stimulations provoked a
      nociceptive flexion reflex response which was measured using an electromyographic
      recording of the bicep femoris muscle. Pain ratings were obtained using a 0-10
      verbal numerical scale. Among schizophrenic participants, the relationship
      between subjective pain, reflex amplitude, and clinical features was
      investigated. The Positive and Negative Syndrome Scale, Calgary Depression Scale
      for Schizophrenia, and Subjective Scale to Investigate Cognition in Schizophrenia
      were used to evaluate clinical features. RESULTS: Compared with controls,
      schizophrenic subjects showed increased sensitivity to acute pain (i.e., lower
      pain thresholds; P = 0.019), but decreased subjective pain sensitization (P =
      0.027). Group differences in subjective pain sensitization were not accompanied
      by group differences in nociceptive reflex activity (P = 0.260), suggesting
      supraspinal origins to the change in pain experienced by schizophrenic subjects.
      Moreover, positive symptoms correlated negatively with pain threshold values
      among schizophrenic participants (r = -0.696, P = 0.012), suggesting that
      distortions of thought and function relate to pain sensitivity in schizophrenic
      patients. CONCLUSION: Results indicate that schizophrenic subjects present a
      specific experimental pain response profile, characterized by elevated
      sensitivity to acute pain but reduced sensitivity to prolonged pain.

PMID- 23170855
TI  - Homoleptic lanthanide 1,2,3-triazolates (infinity)(2-3)[Ln(Tz*)3] and their
      diversified photoluminescence properties.
AB  - The series of homoleptic lanthanide 1,2,3-triazolates (infinity)(3)[Ln(Tz*)3]
      (Ln3+ = lanthanide cation, Tz*- = 1,2,3-triazolate anion, C2H2N3(-)) is completed
      by synthesis of the three-dimensional (3D) frameworks with Ln = La, Ce, Pr, Nd,
      and Sm, and characterization by X-ray powder diffraction, differential thermal
      analysis-thermogravimetry (DTA/TG) investigations and molecular vibration
      analysis. In addition, alpha-(infinity)(2)[Sm(Tz*)3], a two-dimensional polymorph
      of 3D beta-(infinity)(3)[Sm(Tz*)3], is presented including the single crystal
      structure. The 3D lanthanide triazolates form an isotypic series of the formula
      (infinity)(3)[Ln(Tz*)3] ranging from La to Lu, with the exception of Eu, which
      forms a mixed valent metal organic framework (MOF) of different structure and the
      constitution (infinity)(3)[Eu(Tz*)(6+x)(Tz*H)(2-x)]. The main focus of this work
      is put on the investigation of the photoluminescence behavior of lanthanide 1,2,3
      triazolates (infinity)(3)[Ln(Tz*)3] and illuminates that six different
      luminescence phenomena can be found for one series of isotypic compounds. The
      luminescence behavior of the majority of these compounds is based on the
      photoluminescence properties of the organic linker molecules. Differing
      properties are observed for (infinity)(3)[Yb(Tz*)3], which exhibits luminescence
      properties based on charge transfer transitions between the linker and Yb3+ ions,
      and for (infinity)(3)[Ce(Tz*)3] and (infinity)(3)[Tb(Tz*)3], in which the
      luminescence properties are a combination of the ligand and the lanthanide metal.
      In addition, strong inner-filter effects are found in the ligand emission bands
      that are attributed to reabsorption of the emitted light by the trivalent
      lanthanide ions. Antenna effects of varying efficiency are present indicated by
      the energy being transferred to the lanthanide ions subsequent to excitation of
      the ligand. (infinity)(3)[Ce(Tz*)3] shows a 5d-4f induced intense blue emission
      upon excitation with UV light, while (infinity)(3)[Tb(Tz*)3] shows emission in
      the green region of the visible spectrum, which can be identified with 4f-4f
      transitions typical for Tb3+ ions.

PMID- 23170854
TI  - The paracetamol concentration-effect relation in neonates.
AB  - OBJECTIVES: We suggested a loading dose (20 mg . kg(-1) ) followed by 10 mg . kg(
      1) q6h of intravenous (IV) paracetamol to achieve an effect compartment
      concentration of 11 mg . l(-1) in neonates. Since there are no pharmacodynamic
      data to support such an effect compartment concentration, pain scores collected
      in neonates treated with an IV paracetamol loading dose (20 mg . kg(-1) ) were
      used to validate this effect compartment concentration. METHODS: Pain scores
      (Leuven Neonatal Pain Score, LNPS, 0-14) before and 0.5, 1, 2, 3, 4, 5, and 6 h
      after IV paracetamol loading dose administration in neonates to whom IV
      paracetamol was administered as single analgesic (PARANEO,
      www.clinicaltrials.gov, NCT00969176) were collected. Trends were analyzed using
      repeated measures anova. An E(max) model with a delayed response compartment was
      fitted to data using population modeling. RESULTS: Nineteen of 60 neonates
      included in the PARANEO study received monotherapy with IV paracetamol to treat
      mild to moderate pain (e.g., alprostadil administration, delivery related
      trauma). Using repeated measures anova, there was a trend (P = 0.02) for lower
      pain scores within 30 min after administration, with a slight increase in pain
      scores from 5 to 6 h. An E(max) model had a maximum effect of 4.15 pain units, an
      EC(50) of 2.07 mg . l(-1). Equilibration halftime (T(1/2) keo) was 1.58 h.
      CONCLUSION: Intravenous paracetamol is effective for moderate pain. An effect
      compartment concentration of 10 mg . l(-1) (loading dose of 20 mg . kg(-1) ) is
      associated with a pain score reduction of 3.4 LNPS units. This analysis suggests
      a similar paracetamol effect compartment concentration in neonates compared to
      children.

PMID- 23170853
TI  - Influenza in pregnancy.
AB  - The 2009 pandemic served as a strong reminder that influenza-induced disease can
      have a great impact on certain at-risk populations and that pregnant women are
      one such important population. The increased risk of fatal and severe disease in
      these women was appreciated more than 500 years ago, and during the last century,
      pregnant women and their newborns have continued to be greatly affected by both
      seasonal and pandemic influenza. In this review, we briefly discuss the data
      collected both before and after the 2009 pandemic as it relates to the impact of
      influenza on pregnant women and their fetuses/newborns, as well as risk
      variables, clinical features, clues to pathophysiologic mechanisms, and
      approaches to treatment and prevention.

PMID- 23170856
TI  - Historical theses on nursing and caring sciences in Finland: a literature review.
AB  - AIMS: The purpose of this literature review was to review the theses (masters,
      licentiate and doctoral theses) on the history of nursing and caring sciences in
      Finland. The research questions were as follows: 1.What is the number and
      characteristics of these historical theses (target groups, methods and sources)
      on nursing and caring sciences have been produced in Finland? 2.What periods of
      time have been under investigation in these theses? 3.What topics have been
      investigated in these theses? METHODS: The theses on the history of nursing and
      caring sciences were retrieved from the theses index of the universities that
      offer education in nursing and caring sciences in Finland. The literature search
      covered the time period 1979-2010. Altogether, 58 theses were reviewed and
      analysed via content analysis. FINDINGS: Of all of the theses (n = 3969) produced
      in nursing and caring sciences, 58 of them focused on historical topics (<2%).
      The most common target group was healthcare personnel. The most common research
      method was the traditional historical method. Primary and secondary sources were
      used both together and separately. Nearly all of the theses examined the history
      of the 1900s, whereas only a few of them examined time periods before that. The
      four main topics of the theses were nursing practice, nursing education, nursing
      management and philosophy of nursing. The most common topic was nursing practice,
      especially psychiatric nursing. CONCLUSION: Research on the history of nursing
      and caring sciences in Finland has received only marginal attention from
      researchers. This literature review offers a description of the historical
      research produced on nursing and caring sciences and the topics of interest. In
      future, it will be necessary to more closely examine several historical topics
      that have been neglected in the study of nursing and caring sciences.

PMID- 23170857
TI  - Identification and profiling of CXCR3-CXCR4 chemokine receptor heteromer
      complexes.
AB  - BACKGROUND AND PURPOSE: The C-X-C chemokine receptors 3 (CXCR3) and C-X-C
      chemokine receptors 4 (CXCR4) are involved in various autoimmune diseases and
      cancers. Small antagonists have previously been shown to cross-inhibit chemokine
      binding to CXCR4, CC chemokine receptors 2 (CCR2) and 5 (CCR5) heteromers. We
      investigated whether CXCR3 and CXCR4 can form heteromeric complexes and the
      binding characteristics of chemokines and small ligand compounds to these
      chemokine receptor heteromers. EXPERIMENTAL APPROACH: CXCR3-CXCR4 heteromers were
      identified in HEK293T cells using co-immunoprecipitation, time-resolved
      fluorescence resonance energy transfer, saturation BRET and the GPCR-heteromer
      identification technology (HIT) approach. Equilibrium competition binding and
      dissociation experiments were performed to detect negative binding cooperativity.
      KEY RESULTS: We provide evidence that chemokine receptors CXCR3 and CXCR4 form
      heteromeric complexes in HEK293T cells. Chemokine binding was mutually exclusive
      on membranes co-expressing CXCR3 and CXCR4 as revealed by equilibrium competition
      binding and dissociation experiments. The small CXCR3 agonist VUF10661 impaired
      binding of CXCL12 to CXCR4, whereas small antagonists were unable to cross
      inhibit chemokine binding to the other chemokine receptor. In contrast, negative
      binding cooperativity between CXCR3 and CXCR4 chemokines was not observed in
      intact cells. However, using the GPCR-HIT approach, we have evidence for specific
      beta-arrestin2 recruitment to CXCR3-CXCR4 heteromers in response to agonist
      stimulation. CONCLUSIONS AND IMPLICATIONS: This study indicates that heteromeric
      CXCR3-CXCR4 complexes may act as functional units in living cells, which
      potentially open up novel therapeutic opportunities.

PMID- 23170858
TI  - The association of down-regulated toll-like receptor 4 expression with airflow
      limitation and emphysema in smokers.
AB  - BACKGROUND: An association between innate immunity including Toll-like receptors
      (TLRs) and COPD is reported recently; TLR4 deficiency in lung can cause emphysema
      in animals, which is not evident in humans. We analyzed the association of TLR4
      expression, airflow limitation and emphysema in smokers. METHODS: We enrolled
      patients of >=40years old with smoking histories of >=10 pack-years and who had
      undergone lung resection. We measured TLR4 expression in lung lysates. The
      severity of emphysema was evaluated on computed tomography. TLR4 expression was
      also evaluated immunohistochemically. RESULTS: In total, 53 patients were
      enrolled. Forced expiratory volume in one second per forced vital capacity
      (FEV1/FVC) increased (P=0.03) and emphysema score decreased (P=0.01) as TLR4
      expression increased. These were still significant, in multiple regression
      analysis including sex, age, tuberculosis history, smoking history and inhaled
      corticosteroid (ICS) usage. We also classified patients as high, intermediate,
      and low expressers according to TLR4 expression. Although no differences in age,
      gender, tuberculosis, or smoking history were observed among the groups,
      emphysema severity increased significantly (P = 0.02) and FEV1/FVC decreased
      significantly (P = 0.006) in TLR4 low expresser. The difference in TLR4
      expression based on immunohistochemistry was most prominent in bronchial and
      alveolar epithelial cells. CONCLUSION: Down-regulated TLR4 expression in lung was
      associated with emphysema and airflow limitation in smokers.

PMID- 23170859
TI  - Quantitative proteomics by amino acid labeling in foot-and-mouth disease virus
      (FMDV)-infected cells.
AB  - Foot-and-mouth disease virus (FMDV) is an important disease agent that can be
      difficult to effectively eradicate from herds. Because it is an obligate
      intracellular parasite, the virus has multiple effects on the host cell during
      infection. Here, a high-throughput quantitative proteomic approach was used to
      develop an unbiased holistic overview of the protein changes in IBRS-2 cells
      infected with FMDV. Stable isotope labeling with amino acids in cell culture
      (SILAC) combined with LC-MS/MS was performed to identify and quantify 1260
      cellular and 2 viral proteins after 6 h of infection of IBRS-2 cells with FMDV.
      Of these identified and measured cellular protein pairs, 77 were significantly up
      regulated, and 50 were significantly down-regulated based on significance B <=
      0.05. The differentially altered proteins included a number of proteins involved
      in endolysosomal proteases system, cell cycle, cellular growth and proliferation,
      and immune cell trafficking. Selected data were validated by Western blot.
      Ingenuity Pathway Analysis revealed that proteins that changed in response to
      infection could be assigned to defined canonical pathways and functional
      groupings, such as integrin signaling. The obtained data might not only improve
      the understanding of the dynamics of FMDV and host interaction but may also help
      elucidate the pathogenic mechanism of FMDV infection.

PMID- 23170860
TI  - Suppression in retrieval practice, part-set cueing, and negative priming memory:
      the hydrogen model.
AB  - A number of phenomena in memory have been explained using appeals to active
      suppression processes, including retrieval practice, part-set cueing, and the
      negative priming that is observed with associative interference. However, more
      formal attempts to capture such processes have been absent. This paper outlines
      the hydrogen model of memory retrieval, which aims to be a simple model with the
      modest goal of trying to explore what influence suppression would have on memory
      retrieval. This model contains a single activation component and a single
      suppression component in which suppression comes into play only after retrieval
      interference has been detected. This model was created to explore the
      plausibility and viability of ideas about the operation of suppression during
      memory retrieval. For hydrogen, the degree of suppression recruited is
      proportional to the amount of interference experienced. Overall, the pattern of
      human data was captured by the suppression model. 

PMID- 23170861
TI  - "How was your health 3 years ago?" Predicting mortality in older adults using a
      retrospective change measure of self-rated health.
AB  - AIM: Studies have shown better predictive value of self-rated health (SRH) for
      mortality when prospective change in SRH is considered. However, retrospective
      change is more feasible and might have better sensitivity to objective health
      changes. This study compares the predictive value for mortality of
      retrospectively measured change in SRH (based on a "then-test") with current SRH
      and prospectively measured change in SRH. METHODS: Data from two waves of the
      Longitudinal Aging Study Amsterdam (2001-2003 and 2005-2006 [T0 ], n=1894) were
      used. Retrospective change was defined as the difference between SRH at T0
      ("current SRH") and SRH measured with a then-test at T0 , asking for a renewed
      judgement of one's health at the previous wave. Prospective change was defined as
      change in SRH between the two waves. We applied Cox proportional hazards analysis
      to predict 5-year mortality. RESULTS: Having poorer current SRH significantly
      predicted mortality (HR poor vs very good SRH=4.42). Declined SRH was associated
      with higher mortality risk, but only when measured prospectively (one point
      decline vs no change HR=1.33; two points decline HR=1.95). After adjusting for
      current SRH, neither change measure predicted mortality. Results were similar in
      subgroups that did and did not experience incident diseases or limitations
      between the two waves. CONCLUSIONS: Neither retrospective, nor prospective
      changes in SRH improved the prediction of mortality in older adults over current
      SRH. These results imply that using a standard single indicator for self-rated
      health in research or clinical practice might suffice to identify those with a
      high risk of future negative health outcomes.

PMID- 23170862
TI  - Information processing in patients with first episode major depression.
AB  - Few studies have investigated cognitive functioning in a group of patients
      experiencing a first episode of depression. The aim of this study was to
      investigate how patients diagnosed with a first episode of depression perform in
      effortful and non-effortful information processing compared to healthy controls.
      An experimental paradigm based on a visual search test was applied. Thirty-one
      patients and thirty-one healthy controls were included in the study. All patients
      experienced a severe level of symptom load at the time of testing. Results showed
      no significant differences between groups under any of the conditions. Findings
      in the present study indicate that patients with a first episode of depression
      perform equally to healthy controls in tasks requiring visual attention in both
      effortful and non-effortful information processing.

PMID- 23170863
TI  - Cognitive testing in non-demented Turkish immigrants--comparison of the RUDAS and
      the MMSE.
AB  - Methods for culturally and linguistically appropriate cognitive testing of
      elderly minority populations are lacking in Europe. The aim of this study was to
      compare performance on the Rowland Universal Dementia Assessment Scale (RUDAS)
      and the Mini Mental State Examination (MMSE) in Turkish immigrants in Denmark and
      determine the impact of demographic and health-related variables on test
      performance. A sample of non-demented community-dwelling Turkish immigrants was
      recruited from the greater Copenhagen area. All participants completed a
      structured interview regarding demographic, physical and mental health status, as
      well as measures of depression and acculturation, and cognitive testing with the
      RUDAS and the MMSE. A total of 76 non-demented participants aged 50 or more were
      included in the study. The mean performance on the RUDAS and the MMSE was 26.8
      (SD 2.4) and 23.7 (SD 4.3), respectively. In group comparisons, correlation
      analyses and regression analyses, level of schooling represented a more
      significant variable for RUDAS and MMSE performance than any other variable.
      However, the impact of schooling was considerably more pronounced on the MMSE and
      the test was not found to be a valid measure of general cognitive function in
      subjects with less than five years of schooling. Although not entirely free of
      educational bias, the RUDAS can be a valuable supplement to the MMSE for
      assessment of general cognitive function in Turkish minority populations.

PMID- 23170864
TI  - Psychological distress and subjective well-being in partners of somatically ill
      or physically disabled: the Nord-Trondelag Health Study.
AB  - This study investigated the cross-sectional associations between various somatic
      conditions in one partner and the level of distress and well-being in the spouse.
      The study is based on survey data from the Norwegian Nord-Trondelag Health Study,
      HUNT II (1995-1997). A sample of 9,797 married or cohabiting couples with valid
      data on subjective well-being (SWB), psychological distress (Hopkins Symptom
      Check List (SCL)-10) and somatic illness were identified. Regression analyses
      stratified by sex were conducted with SCL-10 and SWB scores as dependent
      variables and a joint somatic score as predictor, including; stroke, cancer,
      angina, myocardial infarction and physical disability (PD). The contribution of
      each somatic condition was also explored. Spouses of persons previously diagnosed
      with at least one somatic condition scored significantly lower on SWB and
      significantly higher on SCL-10 than spouses of healthy persons, though effect
      sizes were small. The effect seems to be at least partly mediated by the ill
      partner's psychological distress. Of the specific conditions, PD had the most
      significant contribution for both genders, though an association between male
      angina and spousal distress/SWB was also demonstrated.

PMID- 23170865
TI  - Self-esteem and emotional health in adolescents--gender and age as potential
      moderators.
AB  - The present paper investigates possible gender and age differences on emotional
      states (depression and anxiety) and self-esteem as well as the association
      between self-esteem and emotional states. The cross-sectional sectional sample
      consists of 1,209 adolescents 13-18 years from public elementary and secondary
      schools in mid-Norway. The results showed that girls reported higher scores on
      state anxiety and state depression, whereas boys consistently scored higher on
      self-esteem in all age groups. Self-esteem was strongly and inversely associated
      with both state depression and state anxiety. An interaction effect of gender by
      self-esteem was found on state depression, where the association was stronger for
      girls than for boys. The associations found give support for the positive role of
      self-esteem in relation to adolescents' emotional health and well-being.

PMID- 23170866
TI  - Development of sense of coherence during two group interventions.
AB  - Burnout is a serious occupational hazard. This study investigated the possibility
      to develop an effective salutogenic group intervention among employees suffering
      from severe burnout symptoms. Participants consisted of employees aged 31 to 59
      years working in different public service occupations, such as police officers,
      tax officers, (and other public service officers), and assigned to three
      different groups: analytic (N = 25), psychodramatic (N = 24) and controls (N =
      28). The intervention comprised 16 separate days over a nine-month period.
      Changes in sense of coherence (SOC) were measured four times with the 13-item
      Orientation to Life Questionnaire during the intervention and at six-month follow
      up, and analyzed by general linear model (GLM) and using Cohen's d to estimate
      effect sizes. Change in SOC between the three groups was statistically
      significant (F(4,148) = 2.65, p = 0.036). The psychodrama group showed a higher
      increase in SOC than the analytic group during the intervention, while the
      improvement in the analytic group was significant during the six-month follow-up.
      Total effect size from baseline to follow-up was in the analytic group 0.71, in
      the psychodrama group 0.47, and in the control group from baseline to end of
      intervention 0.09. The results show that it is possible to improve SOC by group
      intervention in the occupational healthcare context. The dialogue-based analytic
      method and action-based psychodramatic method differ in their specific effects.

PMID- 23170867
TI  - Personality trait inferences of Turkish immigrant and neutral targets: an
      experimental study.
AB  - The study investigated whether personality traits attributed to immigrant targets
      differ from personality inferences made for a neutral target, and whether trait
      attributions differ for assimilated and integrated immigrant targets.
      Participants (n = 340) were randomized to one of three conditions in which they
      read the same story about a person, but where the person was described as either:
      (a) an assimilated Turkish immigrant; (b) an integrated Turkish immigrant; or (c)
      neutral (no nationality or religious practice indicated). Subsequently, they
      rated the personality of the described person on the NEO-Five Factor Inventory
      (observer rating version) and completed the Balanced Inventory of Desirable
      Responding (Impression Management scale) with reference to themselves. Both
      immigrant targets were rated as significantly higher on extraversion and lower on
      neuroticism than the neutral target. The integrated target was rated as more open
      than the neutral target, and as higher than the assimilated target on neuroticism
      when controlling for impression management.

PMID- 23170869
TI  - Lewis acid catalyzed intramolecular condensation of ynol ether-acetals. Synthesis
      of alkoxycycloalkene carboxylates.
AB  - Treatment of ynol ether-tethered dialkyl acetals with catalytic quantities of
      scandium triflate in CH(3)CN gives rise to five-, six-, and seven-membered
      alkoxycycloalkene carboxylates in good to excellent yields. Tri- and
      tetrasubstituted carbocyclic and heterocyclic alkenes may be formed by this
      method, and the products obtained may serve as useful intermediates for natural
      product synthesis.

PMID- 23170870
TI  - Candiduria in haematologic malignancy patients without a urinary catheter:
      nothing more than a frailty marker?
AB  - There is scarcity of data regarding significance of candiduria in patients with
      haematologic malignancies and its association with invasive candidiasis. To that
      end, we retrospectively evaluated all hospitalised, non-intensive care unit
      patients with haematologic malignancies and candiduria during a 10-year period
      (2001-2011). To decrease the possibility of bladder colonisation and sample
      contamination, we excluded all patients with candiduria who had urinary catheters
      and those with concomitant bacteriuria. Twenty-four such patients (21 females)
      were identified, with median age at diagnosis 62 years (range, 20-82 years).
      Acute leukaemia was the most common underlying disease (54%); 62% of these cases
      were not in remission. Twenty-nine percent of the patients had diabetes mellitus
      and 25% were neutropenic. The most common isolated Candida species was Candida
      glabrata (37%), followed by C. albicans (29%). Only 8% of them had urinary tract
      infection symptoms. However, 88% received systemic antifungals. Candidemia and
      crude mortality rates at 4 weeks were low (4% and 12% respectively). Isolated
      candiduria in patients with haematologic malignancies has risk factors similar to
      those in other hospitalised patients, and it does not seem to be a strong
      predictor of subsequent invasive candidiasis.

PMID- 23170871
TI  - True density and apparent density during the drying process for vegetables and
      fruits: a review.
AB  - This review presents the concepts involved in determining the density of
      foodstuffs, and summarizes the volumetric determination techniques used to
      calculate true density and apparent density in foodstuffs exposed to the drying
      process. The behavior of density with respect to moisture content (X) and drying
      temperature (T) is presented and explained with a basis in changes in structure,
      conformation, chemical composition, and second-order phase changes that occur in
      the processes of mass and heat transport, as reported to date in the literature.
      A review of the empirical and theoretical equations that represent density is
      presented, and their application in foodstuffs is discussed. This review also
      addresses cases with nonideal density behavior, including variations in rho(s) 
      and rho(w)  as a function of the inside temperature of the material, depending on
      drying conditions (X, T). A compilation of studies regarding the density of
      dehydrated foodstuffs is also presented.

PMID- 23170872
TI  - Genetic linkage maps for Asian and American lotus constructed using novel SSR
      markers derived from the genome of sequenced cultivar.
AB  - BACKGROUND: The genus Nelumbo Adans. comprises two living species, N. nucifera
      Gaertan. (Asian lotus) and N. lutea Pers. (American lotus). A genetic linkage map
      is an essential resource for plant genetic studies and crop improvement but has
      not been generated for Nelumbo. We aimed to develop genomic simple sequence
      repeat (SSR) markers from the genome sequence and construct two genetic maps for
      Nelumbo to assist genome assembly and integration of a genetic map with the
      genome sequence. RESULTS: A total of 86,089 SSR motifs were identified from the
      genome sequences. Di- and tri-nucleotide repeat motifs were the most abundant,
      and accounted for 60.73% and 31.66% of all SSRs, respectively. AG/GA repeats
      constituted 51.17% of dinucleotide repeat motifs, followed by AT/TA (44.29%). Of
      500 SSR primers tested, 386 (77.20%) produced scorable alleles with an average of
      2.59 per primer, and 185 (37.00%) showed polymorphism among two parental
      genotypes, N. nucifera 'Chinese Antique' and N. lutea 'AL1', and six progenies of
      their F1 population. The normally segregating markers, which comprised 268 newly
      developed SSRs, 37 previously published SSRs and 53 sequence-related amplified
      polymorphism markers, were used for genetic map construction. The map for Asian
      lotus was 365.67 cM with 47 markers distributed in seven linkage groups. The map
      for American lotus was 524.51 cM, and contained 177 markers distributed in 11
      genetic linkage groups. The number of markers per linkage group ranged from three
      to 34 with an average genetic distance of 3.97 cM between adjacent markers.
      Moreover, 171 SSR markers contained in linkage groups were anchored to 97 genomic
      DNA sequence contigs of 'Chinese Antique'. The 97 contigs were merged into 60
      scaffolds. CONCLUSION: Genetic mapping of SSR markers derived from sequenced
      contigs in Nelumbo enabled the associated contigs to be anchored in the linkage
      map and facilitated assembly of the genome sequences of 'Chinese Antique'. The
      present study reports the first construction of genetic linkage maps for Nelumbo,
      which can serve as reference linkage maps to accelerate characterization
      germplasm, genetic mapping for traits of economic interest, and molecular
      breeding with marker-assisted selection.

PMID- 23170873
TI  - Nonclinical strategy considerations for safety pharmacology: evaluation of
      biopharmaceuticals.
AB  - INTRODUCTION: Biopharmaceuticals, such as monoclonal antibodies and recombinant
      peptides, are important therapeutics to treat human disease. Key features of
      biopharmaceuticals that make them innovative medicines are their clinical
      effectiveness, high specificity for their human target, long half-life and target
      coverage, and low risk for "off-target" pharmacology. AREAS COVERED: This paper
      describes nonclinical safety pharmacology assessment of biopharmaceuticals with
      an emphasis on special considerations needed for these agents. Insight is
      provided on various approaches to conduct safety pharmacology studies for such
      therapeutics, including appropriate integration into non-rodent toxicity studies.
      EXPERT OPINION: The safety pharmacology evaluation of biopharmaceuticals requires
      a science-based, case-by-case approach, as each biological modality will have
      unique pharmacological characteristics that influence the overall nonclinical
      safety assessment strategy. The integration of safety pharmacology endpoints into
      general (repeat-dose) toxicity studies is a rational paradigm for assessing
      potential changes in the cardiovascular, central nervous, and respiratory
      systems, but requires thoughtful and practical planning. In some cases,
      especially based on target-pharmacology concerns, dedicated and optimally
      designed safety pharmacology studies may be needed to assess the functional risk
      of a new biopharmaceutical. For example, cardiovascular telemetry studies may be
      needed to detect small changes in arterial blood pressure after acute and chronic
      exposure.

PMID- 23170874
TI  - Discontinuation of reimbursement of benzodiazepines in the Netherlands: does it
      make a difference?
AB  - BACKGROUND: In an attempt to control chronic benzodiazepine use and its costs in
      the Netherlands, health care insurance reimbursement of this medication was
      stopped on January 1st 2009. This study investigates whether benzodiazepine
      prescriptions issued by general practitioners changed during the first two years
      following implementation of this regulation. METHODS: Registry study based on
      data from all benzodiazepine users derived from the Registration Network
      Groningen. This general practice-based research network collects longitudinal
      data on the primary care administered to about 30,000 patients. Based on the
      number of quarterly accumulated prescription days, a comparison was made of
      benzodiazepine prescriptions issued between 2007/2008 and 2009/2010. Also
      investigated was which type of user (i.e. short-term or long-term) showed the
      most change. RESULTS: Information on benzodiazepine prescriptions among 5,200
      patients from 16 consecutive trimesters between 2007 and 2010 was available for
      analysis. A significant reduction in prescription days was observed between
      2007/2008 and 2009/2010. Overall, an estimated 1.73 (CI:-1.94 to -1.53; p<0.001)
      days were less prescribed per trimester after the termination of reimbursement.
      In particular, short-term users experienced a reduction in prescription days in
      2009 and 2010. The number of long-term users decreased by 2.3%, while the number
      of individuals that did not use increased by 4.2%. CONCLUSIONS: A total reduction
      of almost 14 prescription days was observed over eight trimesters after
      implementation of the regulation to terminate the reimbursement of
      benzodiazepines. Short-term users were mainly responsible for this reduction in
      prescription days in 2009 and 2010. Although long-term users did not alter their
      benzodiazepine use in 2009 and 2010, the number of long-term users decreased
      slightly.

PMID- 23170875
TI  - Nurses' experiences of participation in a research and development programme.
AB  - AIMS AND OBJECTIVES: To describe clinical nurses' experience of participating in
      a Research and Development (R&D) programme and its influence on their research
      interest and ability to conduct and apply nursing research. BACKGROUND: To
      stimulate nurses' research interest and to overcome barriers for building
      research capacity in nursing, there is a need for sustainable research
      programmes. A two-year programme was designed for nurses, to take part in both an
      academic education for master and research seminars and workshops to conduct a
      research project from idea to publication. DESIGN: A qualitative approach using
      using focus group interviews. METHODS: Registered nurses (n=12) with a bachelor's
      degree in nursing, participated. Data were collected in focus group interviews,
      after one year and when the programme ended. Content analysis was used to analyse
      the data. RESULTS: The findings consist of two themes: being a traveller in the
      world of nursing research, which included three categories, and experiencing
      professional growth as a result of nursing research training, in both cases
      focusing on the experience of students involved in a cohesive programme which
      included four categories: discovering new dimensions of clinical nursing
      practice; selected and confirmed; supported by professional others; development
      of professional self-concept. CONCLUSIONS: To support early career researchers,
      there is a need for strong leadership, an organisational and supportive
      infrastructure underpinning research capability building in nurses. In this
      context, research strategies, programmes and collaboration between leaders of
      academia and clinical institutions appear to be essential. RELEVANCE TO CLINICAL
      PRACTICE: The R&D programme illustrates an effective way of stimulating nurses'
      lifelong learning by building the capacity to conduct and apply nursing research
      in clinical practice. The structure of the programme can be used as a model in
      other contexts.

PMID- 23170876
TI  - Costs of inpatient treatment for multi-drug-resistant tuberculosis in South
      Africa.
AB  - BACKGROUND: In South Africa, patients with multi-drug-resistant tuberculosis (MDR
      TB) are hospitalised from MDR-TB treatment initiation until culture conversion.
      Although MDR-TB accounts for <3% of incident TB in South Africa, 55% of the
      public sector TB budget is spent on MDR-TB. To inform new strategies for MDR-TB
      management, we estimated the per-patient cost (USD 2011) of inpatient MDR-TB
      treatment. METHODS: All resources used by patients admitted to the MDR-TB
      hospital with confirmed MDR-TB from March 2009 to February 2010 were abstracted
      from patient records for up to 12 months after initial admission or until the
      earliest of final discharge, abscondment or death. Costs of hospital stay/day
      were estimated from hospital expenditure records and costs for drugs, laboratory
      tests, radiography and surgery from public sector sources. 133 patients met study
      inclusion criteria of whom 121 had complete cost records. RESULTS: By 12 months,
      86% were discharged with culture conversion, 8% died in hospital, 2% were still
      admitted, and 3% had absconded. The mean hospital stay was 105 days. The mean
      total cost per patient was $17 164, of which 95% were hospitalisation costs
      (buildings, staff, etc.) and <= 2% each for MDR-TB drugs ($380); TB laboratory
      tests, including drug susceptibility testing ($236); and other costs.
      CONCLUSIONS: The inpatient cost per patient treated for MDR-TB is more than 40
      times the cost of treating drug-susceptible TB in South Africa. There is
      potential for substantial cost savings from improved management of drug
      susceptible TB and shifting to a model of decentralised, outpatient MDR
      treatment.

PMID- 23170878
TI  - Low serum albumin level as an independent risk factor for the onset of pressure
      ulcers in intensive care unit patients.
AB  - Critically ill patients are at high risk of developing pressure ulcers (PUs) and
      patients who develop PUs remain significantly longer in the intensive care unit
      (ICU) with significantly increased morbidity and mortality. Therefore, the
      identification of patients at truly increased risk is important. The aim of this
      study was to examine the association of low serum albumin present at admission in
      ICU patients with the onset of PUs. We conducted a retrospective cohort study on
      610 patients who were admitted to intensive care unit. Level of serum albumin and
      other biochemical indices, recorded at the time of admission, were collected. We
      collected information about PU occurrence after admission and conducted a
      statistical analysis with biomarkers at ICU admission and during hospital stay.
      The incidence of PU in the ICUs was 31% and about 70% of patients with PUs had
      hypoalbuminemia at admission. The lowest values of serum albumin in patients with
      PUs were directly proportional to the severity of ulcers. In this study, we found
      a close association between serum albumin and PUs. In fact serum albumin was
      negatively correlated with PU and may be considered one of the independent
      determinants of PU occurrence in patients admitted to ICUs. 

PMID- 23170877
TI  - Label-free quantitative proteomics of CD133-positive liver cancer stem cells.
AB  - BACKGROUND: CD133-positive liver cancer stem cells, which are characterized by
      their resistance to conventional chemotherapy and their tumor initiation ability
      at limited dilutions, have been recognized as a critical target in liver cancer
      therapeutics. In the current work, we developed a label-free quantitative method
      to investigate the proteome of CD133-positive liver cancer stem cells for the
      purpose of identifying unique biomarkers that can be utilized for targeting liver
      cancer stem cells. Label-free quantitation was performed in combination with ID
      based Elution time Alignment by Linear regression Quantitation (IDEAL-Q) and
      MaxQuant. RESULTS: Initially, IDEAL-Q analysis revealed that 151 proteins were
      differentially expressed in the CD133-positive hepatoma cells when compared with
      CD133-negative cells. We then analyzed these 151 differentially expressed
      proteins by MaxQuant software and identified 10 significantly up-regulated
      proteins. The results were further validated by RT-PCR, western blot, flow
      cytometry or immunofluorescent staining which revealed that prominin-1, annexin
      A1, annexin A3, transgelin, creatine kinase B, vimentin, and EpCAM were indeed
      highly expressed in the CD133-positive hepatoma cells. CONCLUSIONS: These
      findings confirmed that mass spectrometry-based label-free quantitative
      proteomics can be used to gain insights into liver cancer stem cells.

PMID- 23170879
TI  - Fano resonances in all-dielectric oligomers.
AB  - We demonstrate that light scattering by all-dielectric oligomers exhibits well
      pronounced Fano resonances with strong suppression of the scattering cross
      section. Our analysis reveals that this type of the Fano resonance originates
      from the optically induced magnetic dipole modes of individual high-dielectric
      nanoparticles. By comparing to the plasmonic analogues, we observe that Fano
      resonances in all-dielectric oligomers are less sensitive to structural
      variations, which makes them promising for future applications in nanophotonics.

PMID- 23170881
TI  - Resolving differences in substrate specificities between human and parasite
      phosphoribosyltransferases via analysis of functional groups of substrates and
      receptors.
AB  - We herein review experimental and theoretical approaches widely applied to
      delineation of the differences in substrate specificities between human and
      parasite phosphoribosyltransferases (PRTases), the latter of which are key
      targets for treatment of diseases caused by parasites. Standard Molecular
      Dynamics (MD) simulations have been applied to determine why the human PRTase
      prefers guanine over xanthine, whereas the Tritrichomonas foetus enzyme exhibits
      only a slight preference. We analyze this problem with the aid of standard MD
      simulations, as well as constant-pH MD simulations. Comparison of results of the
      two approaches reveals substantial differences, e.g. several Asp and Glu residues
      in the parasite enzyme, and one Glu residue in the human enzyme, are predicted to
      be permanently or frequently protonated during constant-pH simulations, whereas
      standard MD simulations assume that these residues are always ionized. Most
      interesting is the observation of a large conformational change, leading to
      tighter binding of the ligand, observed in constant-pH MD simulations of the
      parasite PRTase complexed with XMP, and lack of such a change in the human enzyme
      complexed with XMP.

PMID- 23170880
TI  - The role of protonation states in ligand-receptor recognition and binding.
AB  - In this review we discuss the role of protonation states in receptor-ligand
      interactions, providing experimental evidences and computational predictions that
      complex formation may involve titratable groups with unusual pKa's and that
      protonation states frequently change from unbound to bound states. These
      protonation changes result in proton uptake/release, which in turn causes the pH
      dependence of the binding. Indeed, experimental data strongly suggest that almost
      any binding is pH-dependent and to be correctly modeled, the protonation states
      must be properly assigned prior to and after the binding. One may accurately
      predict the protonation states when provided with the structures of the unbound
      proteins and their complex; however, the modeling becomes much more complicated
      if the bound state has to be predicted in a docking protocol or if the structures
      of either bound or unbound receptor-ligand are not available. The major
      challenges that arise in these situations are the coupling between binding and
      protonation states, and the conformational changes induced by the binding and
      ionization states of titratable groups. In addition, any assessment of the
      protonation state, either before or after binding, must refer to the pH of
      binding, which is frequently unknown. Thus, even if the pKa's of ionizable groups
      can be correctly assigned for both unbound and bound state, without knowing the
      experimental pH one cannot assign the corresponding protonation states, and
      consequently one cannot calculate the resulting proton uptake/release. It is
      pointed out, that while experimental pH may not be the physiological pH and
      binding may involve proton uptake/release, there is a tendency that the native
      receptor-ligand complexes have evolved toward specific either subcellular or
      tissue characteristic pH at which the proton uptake/release is either minimal or
      absent.

PMID- 23170883
TI  - Potential application of network descriptions for understanding conformational
      changes and protonation states of ABC transporters.
AB  - The ABC (ATP Binding Cassette) transporter protein superfamily comprises a large
      number of ubiquitous and functionally versatile proteins conserved from archaea
      to humans. ABC transporters have a key role in many human diseases and also in
      the development of multidrug resistance in cancer and in parasites. Although a
      dramatic progress has been achieved in ABC protein studies in the last decades,
      we are still far from a detailed understanding of their molecular functions.
      Several aspects of pharmacological ABC transporter targeting also remain unclear.
      Here we summarize the conformational and protonation changes of ABC transporters
      and the potential use of this information in pharmacological design. Network
      related methods, which recently became useful tools to describe protein structure
      and dynamics, have not been applied to study allosteric coupling in ABC proteins
      as yet. A detailed description of the strengths and limitations of these methods
      is given, and their potential use in describing ABC transporter dynamics is
      outlined. Finally, we highlight possible future aspects of pharmacological
      utilization of network methods and outline the future trends of this exciting
      field.

PMID- 23170884
TI  - Protonation states and conformational ensemble in ligand-based QSAR modeling.
AB  - Drug affinity and function depend on the different protonation species (present
      in the biological context) that generate different conformational ensembles with
      different structural features and, hence, different physico-chemical properties.
      In the present review article these strongly interdependent structural features
      will be considered for their crucial role in ligand-based QSAR modeling and drug
      design by using quantum chemical electronic/reactivity descriptors and molecular
      shape description. Some selected and relevant examples illustrate the role of
      these molecular descriptors, computed on the bioactive protonation states and
      conformers, as determinant factors in mechanistic/causative QSAR analysis.

PMID- 23170882
TI  - Rigorous incorporation of tautomers, ionization species, and different binding
      modes into ligand-based and receptor-based 3D-QSAR methods.
AB  - Speciation of drug candidates and receptors caused by ionization, tautomerism,
      and/or covalent hydration complicates ligandand receptor-based predictions of
      binding affinities by 3-dimensional structure-activity relationships (3D-QSAR).
      The speciation problem is exacerbated by tendency of tautomers to bind in
      multiple conformations or orientations (modes) in the same binding site. New
      forms of the 3D-QSAR correlation equations, capable of capturing this complexity,
      can be developed using the time hierarchy of all steps that lie behind the
      monitored biological process - binding, enzyme inhibition or receptor activity.
      In most cases, reversible interconversions of individual ligand and receptor
      species can be treated as quickly established equilibria because they are
      finished in a small fraction of the exposure time that is used to determine
      biological effects. The speciation equilibria are satisfactorily approximated by
      invariant fractions of individual ligand and receptor species for buffered
      experimental or in vivo conditions. For such situations, the observed drug
      receptor association constant of a ligand is expressed as the sum of products,
      for each ligand and receptor species pair, of the association microconstant and
      the fractions of involved species. For multiple binding modes, each microconstant
      is expressed as the sum of microconstants of individual modes. This master
      equation leads to new 3D-QSAR correlation equations integrating the results of
      all molecular simulations or calculations, which are run for each ligand-receptor
      species pair separately. The multispecies, multimode 3D-QSAR approach is
      illustrated by a ligand-based correlation of transthyretin binding of thyroxine
      analogs and by a receptor-based correlation of inhibition of MK2 by
      benzothiophenes and pyrrolopyrimidines.

PMID- 23170885
TI  - Nucleotide binding affects intrinsic dynamics and structural communication in Ras
      GTPases.
AB  - The Ras superfamily comprises many guanine nucleotide-binding proteins (G
      proteins) that are essential to intracellular signal transduction. These proteins
      act biologically as molecular switches, which, cycling between OFF and ON states,
      play fundamental role in cell biology. This review article summarizes the
      inferences from the widest computational analyses done so far on Ras GTPases
      aimed at providing a comprehensive structural/dynamic view of the trans-family
      and family-specific functioning mechanisms. These variegated comparative analyses
      could infer the evolutionary and intrinsic flexibilities as well as the
      structural communication features in the most representative G protein families
      in different functional states. In spite of the low sequence similarities, the
      members of the Ras superfamily share the topology of the Ras-like domain,
      including the nucleotide binding site. GDP and GTP make very similar interactions
      in all GTPases and differences in their binding modes are localized around the
      gamma-phosphate of GTP. Remarkably, such subtle local differences result in
      significant differences in the functional dynamics and structural communication
      features of the protein. In Ras GTPases, the nucleotide plays a central and
      active role in dictating functional dynamics, establishing the major structure
      network, and mediating the communication paths instrumental in function retention
      and specialization. Collectively, the results of these studies support the
      speculation that an "extended conformational selection model" that embraces a
      repertoire of selection and adjustment processes is likely more suitable to
      describe the nucleotide behavior in these important molecular switches.

PMID- 23170886
TI  - Effects of the protonation state of the catalytic residues and ligands upon
      binding and recognition in targeted proteins of HIV-1 and influenza viruses.
AB  - The determination of the protonation state of the functional groups of ligands,
      and the amino acid residues with electrically charged side chains (His, Lys, Arg,
      Asp and Glu) or the nucleotide bases of the nucleic acids that they interact
      with, is important for ligand binding and recognition, the enzyme activity and
      reaction mechanism, and protein folding/unfolding and stability. Herein, the
      effects of different protonation state assignments of the small substrate and
      inhibitors and the critical residues on the reverse transcriptase and protease of
      human immunodeficiency virus type 1 (HIV-1) and the M2 proton channel of
      influenza A virus are reviewed. Theoretical studies on these topics are
      summarized and compared with the experimental data.

PMID- 23170887
TI  - Calculation methods for the enhancement of pharmaceutical properties in small
      molecules: estimating the cationic pKa.
AB  - In this review, a summary of methodologies is covered to enable medicinal
      chemists to access an overview of pK(a) estimation devices. In order to stave
      overutilization of costly synthetic resources, the chemist requires an accurate
      and computationally tractable solution for estimating a pK(a) of a candidate
      molecule. We focus on the cationic moieties, since they are so fundamentally
      important in the chemistry of drugs, and possess unique requirements to obtain a
      reasonably reliable pK(a) estimation.

PMID- 23170888
TI  - Correct protonation states and relevant waters = better computational
      simulations?
AB  - The unique physicochemical properties of water make it the most important
      molecule for life. Water molecules have many roles, direct and indirect, related
      to both biological structure and function. This paper: 1) reviews tools for the
      prediction of water conservation in and around protein active sites, by empirical
      (knowledge-based) algorithms and by methods based on thermodynamics principles;
      2) reviews principles and approaches to predict pK(a) for both protein residue
      ensembles and for ligands; and 3) discusses the HINT biomolecular interaction
      model and forcefield - based on experimental measurements of LogP(o/w), the 1
      octanol/water partition coefficient, which implicitly incorporates all solution
      phenomena like these, and others like tautomerism and entropy. Lastly, it must be
      considered that the "real" biological environment is a continuum of nano-states
      and it may not be possible to represent it as a single discrete all-atom model.

PMID- 23170889
TI  - Protonation States in molecular dynamics simulations of peptide folding and
      binding.
AB  - Peptides are important signaling modules, acting both as individual hormones and
      as parts of larger molecules, mediating their protein-protein interactions. Many
      peptidic and peptidomimetic drugs have reached the marketplace and opportunities
      for peptide-based drug discovery are on the rise. pH-dependent behavior of
      peptides is well documented in the context of misfolding diseases and peptide
      translocation. Changes in the protonation states of peptide residues often have a
      crucial effect on a peptide's structure, dynamics and function, which may be
      exploited for biotechnological applications. The current review surveys the
      increasing levels of sophistication in the treatment of protonation states in
      computational studies involving peptides. Specifically we describe I) the common
      practice of assigning a single protonation state and using it throughout the
      dynamic simulation, II) approaches that consider multiple protonation states and
      compare computed observables to experimental ones, III) constant pH molecular
      dynamics methods that couple changes in protonation states with conformational
      dynamics "on the fly". Applications of conformational dynamics treatment of
      peptides in the context of binding, folding and interactions with the membrane
      are presented, illustrating the growing body of work in this field and
      highlighting the importance of careful handling of protonation states of peptidic
      residues.

PMID- 23170890
TI  - Protein: ligand recognition: simple models for electrostatic effects.
AB  - Free energy simulations are a powerful tool to study molecular recognition. The
      most rigorous variants can provide in depth understanding for a particular
      system, but are not suited for high throughput application to large libraries of
      compounds. Related, but less expensive methods are increasingly popular,
      including continuum electrostatic methods like PBSA ("Poisson-Boltzmann Surface
      Area") and Linear Response or Linear Interaction Energy methods (LRA, LIE). Here,
      we review the theoretical background of these methods and provide a unified
      framework. We focus on the electrostatic contributions to the binding free
      energy, analyzing nonpolar contributions more briefly. The methods reviewed
      introduce a multi-step pathway for ligand unbinding, with distinct steps that
      uncharge the bound ligand, then recharge the unbound ligand. They assume that the
      system responds to the charging/uncharging in a linear way. With this
      approximation, the free energy can be described by its one or two first
      derivatives with respect to a progress variable. The methods can then be
      classified according to which states of the system are actually simulated and the
      number of free energy derivatives (one or two) that are employed. The analysis
      should help clarify the relations between several important free energy methods
      and the approximations they make. It can suggest new ways to test them, and
      provide routes for their improvement.

PMID- 23170891
TI  - On the active site protonation state in aspartic proteases: implications for drug
      design.
AB  - Aspartic proteases (AP) are a family of important hydrolytic enzymes in medicinal
      chemistry, since many of its members have become therapeutical targets for a wide
      variety of diseases from AIDS to Alzheimer. The enzymatic activity of these
      proteins is driven by the Asp dyad, a pair of active site Asp residues that
      participate in the hydrolysis of peptides. Hence, the protonation state of these
      and other acidic residues present in these enzymes determines the catalytic rate
      and the affinity for an inhibitor at a given pH. In the present work we have
      reviewed the effect of the protonation states of the titratable residues in AP's
      both on catalysis and inhibition in this family of enzymes. The first section
      focuses on the details of the catalytic reaction mechanism picture brought about
      by a large number of kinetic, crystallographic and computational chemistry
      analyses. The results indicate that although the mechanism is similar in both
      retroviral and eukaryotic enzymes, there are some clear differences. For
      instance, while in the former family branch the binding of the substrate induces
      a mono-ionic charge state for the Asp dyad, this charge state seems to be already
      present in the unbound state of the eukaryotic enzymes. In this section we have
      explored as well the possible existence of low barrier hydrogen bonds (LBHB's) in
      the enzymatic path. Catalytic rate enhancement in AP's could in part be explained
      by the lowering of the barrier for proton transfer in a hydrogen bond from donor
      to acceptor, which is a typical feature of LBHB's. Review of the published work
      indicates that the experimental support for this type of bonds is rather scarce
      and it may be more probable in the first stages of the hydrolytic mechanism in
      retroviral proteases. The second section deals with the effect of active site
      protonation state on inhibitor binding. The design of highly potent AP
      inhibitors, that could be the basis for drug leads require a deep knowledge of
      the protonation state of the active site residues induced by their presence. This
      vital issue has been tackled by experimental techniques like NMR, X-ray
      crystallography, calorimetric and binding kinetic techniques. Recently, we have
      developed a protocol that combines monitoring the pH effect on binding affinities
      by SPR methods and rationalization of the results by molecular mechanics based
      calculations. We have used this combined method on BACE-1 and HIV-1 PR, two
      important therapeutic targets. Our calculations are able to reproduce the
      inhibitor binding trends to either enzyme upon a pH increase. The results
      indicate that inhibitors that differ in the Asp dyad binding fragments will
      present different binding affinity trends upon a pH increase. Our calculations
      have enabled us to predict the protonation states at different pH values that
      underlie the above mentioned trends. We have found out that these results have
      many implications not only for in silico hit screening campaigns aimed at finding
      high affinity binders, but also (in the case of BACE-1) for the discovery of cell
      active compounds.

PMID- 23170893
TI  - Protonation states and conformational dynamics in ligand-target recognition and
      binding.

PMID- 23170892
TI  - Intrinsic disorder-based protein interactions and their modulators.
AB  - It is clear now that proteins lacking ordered structure, generally known as
      intrinsically disordered proteins (IDPs), possess numerous biological functions
      that complement functional repertoires of ordered proteins. IDPs are common in
      nature, and abundantly found to be involved in the pathogenesis of various
      diseases. These proteins participate in various biological processes and play
      crucial roles in regulation of functions of their binding partners. Often,
      disorder-to-order transition induced by the IDP binding to a specific partner
      defines the low-affinity - high-specificity signaling interactions. Although many
      IDPs undergo a disorder-to-order transition upon binding, large fraction of IDPs
      can preserve significant amount of disorder even in their bound states. IDPs can
      participate in one-tomany and many-to-one interactions, where one intrinsically
      disordered protein region (IDPR) binds to multiple partners potentially gaining
      very different structures in the bound state, or where multiple unrelated
      IDPs/IDPRs bind to one partner. Binding functions of IDPs and IDPRs are
      controlled by various means, such as numerous posttranslational modifications and
      alternative splicing. Some of the aspects of the intrinsic disorder-based protein
      interactions and modes of their regulation are considered in this review.

PMID- 23170894
TI  - Engineering natural materials as surface-enhanced Raman spectroscopy substrates
      for in situ molecular sensing.
AB  - Surface-enhanced Raman spectroscopy (SERS) is a powerful analytical tool.
      However, its applications for in situ detection of target molecules presented on
      diverse material surfaces have been hindered by difficulties in rapid fabricating
      SERS-active substrates on the surfaces of these materials through a simple, low
      cost, and portable approach. Here, we demonstrate our attempt to address this
      issue by developing a facile and versatile method capable of in situ generating
      silver nanoparticle film (SNF) on the surfaces of both artificial and natural
      materials in a simple, cheap, practical, and disposable manner. Taking advantage
      of the high SERS enhancement ability of the prepared SNF, the proposed strategy
      can be used for in situ inspecting herbicide and pesticide residues on
      vegetables, as well as the abuse of antiseptic in aquaculture industry.
      Therefore, it opens new avenues for advancing the application prospects of SERS
      technique in the fields of food safety, drug security, as well as environment
      monitoring.

PMID- 23170895
TI  - Exploring the relationship between population density and maternal health
      coverage.
AB  - BACKGROUND: Delivering health services to dense populations is more practical
      than to dispersed populations, other factors constant. This engenders the
      hypothesis that population density positively affects coverage rates of health
      services. This hypothesis has been tested indirectly for some services at a local
      level, but not at a national level. METHODS: We use cross-sectional data to
      conduct cross-country, OLS regressions at the national level to estimate the
      relationship between population density and maternal health coverage. We
      separately estimate the effect of two measures of density on three population
      level coverage rates (6 tests in total). Our coverage indicators are the fraction
      of the maternal population completing four antenatal care visits and the
      utilization rates of both skilled birth attendants and in-facility delivery. The
      first density metric we use is the percentage of a population living in an urban
      area. The second metric, which we denote as a density score, is a relative
      ranking of countries by population density. The score's calculation discounts a
      nation's uninhabited territory under the assumption those areas are irrelevant to
      service delivery. RESULTS: We find significantly positive relationships between
      our maternal health indicators and density measures. On average, a one-unit
      increase in our density score is equivalent to a 0.2% increase in coverage rates.
      CONCLUSIONS: Countries with dispersed populations face higher burdens to achieve
      multinational coverage targets such as the United Nations' Millennial Development
      Goals.

PMID- 23170896
TI  - Phase I study of TP300 in patients with advanced solid tumors with
      pharmacokinetic, pharmacogenetic and pharmacodynamic analyses.
AB  - BACKGROUND: A Phase I dose escalation first in man study assessed maximum
      tolerated dose (MTD), dose-limiting toxicity (DLT) and recommended Phase II dose
      of TP300, a water soluble prodrug of the Topo-1 inhibitor TP3076, and active
      metabolite, TP3011. METHODS: Eligible patients with refractory advanced solid
      tumors, adequate performance status, haematologic, renal, and hepatic function.
      TP300 was given as a 1-hour i.v. infusion 3-weekly and pharmacokinetic (PK)
      profiles of TP300, TP3076 and TP3011 were analysed. Polymorphisms in CYP2D6, AOX1
      and UGT1A1 were studied and DNA strand-breaks measured in peripheral blood
      mononuclear cells (PBMCs). RESULTS: 32 patients received TP300 at 1, 2, 4, 6, 8,
      10, 12 mg/m(2). MTD was 10 mg/m(2); DLTs at 12 (2/4 patients) and 10 mg/m(2)
      (3/12) included thrombocytopenia and febrile neutropenia; diarrhoea was uncommon.
      Six patients (five had received irinotecan), had stable disease for 1.5-5 months.
      TP3076 showed dose proportionality in AUC and Cmax from 1-10 mg/m(2). Genetic
      polymorphisms had no apparent influence on exposure. DNA strand-breaks were
      detected after TP300 infusion. CONCLUSIONS: TP300 had predictable hematologic
      toxicity, and diarrhoea was uncommon. AUC at MTD is substantially greater than
      for SN38. TP3076 and TP3011 are equi-potent with SN38, suggesting a PK advantage.
      TRIAL REGISTRATION: EU-CTR2006-001345-33.

PMID- 23170898
TI  - Reexamine the study on abuse potential of Remoxy((r)) : what was missing?

PMID- 23170897
TI  - Role of non-prolamin proteins and low molecular weight redox agents in protein
      folding and polymerization in wheat grains and influence on baking quality
      parameters.
AB  - The various enzyme systems and low molecular weight (LMW) redox agents are
      related to the folding and polymerization of prolamins in the ripening wheat
      grains and the formation of baking quality. Protein disulfide isomerases (PDIs)
      and cyclophylins accelerate "correct" folding of prolamins, which is most likely
      necessary for the subsequent formation of the macromolecular structure of the
      gluten protein matrix. PDIs are also involved in the polymerization of prolamins,
      catalyzing the oxidation of protein sulfhydryl groups. Molecular chaperone
      binding BiP protein facilitates folding of prolamins, with its role increasing in
      the stressful conditions. Reducing systems of thioredoxin and glutaredoxin, LMW
      redox pairs GSH/GSSG and Asc/DHAsc, thiol oxidases, and lipoxygenases (LOXs)
      regulate redox balance and the rate of polymerization of prolamins at the
      different stages of grain ripening. Additionally, LOX is probably involved in the
      protein-starch-lipid interactions between the starch granule and the protein
      matrix, mediated by puroindolines, determining the formation of grain texture. It
      is assumed that the high variability of baking quality in different environmental
      conditions is due to the interaction of labile enzyme systems with the storage
      proteins in the developing wheat caryopsis.

PMID- 23170899
TI  - Alcohol beverage control, privatization and the geographic distribution of
      alcohol outlets.
AB  - BACKGROUND: With Pennsylvania currently considering a move away from an Alcohol
      Beverage Control state to a privatized alcohol distribution system, this study
      uses a spatial analytical approach to examine potential impacts of privatization
      on the number and spatial distribution of alcohol outlets in the city of
      Philadelphia over a long time horizon. METHODS: A suite of geospatial data were
      acquired for Philadelphia, including 1,964 alcohol outlet locations, 569,928 land
      parcels, and school, church, hospital, park and playground locations. These data
      were used as inputs for exploratory spatial analysis to estimate the expected
      number of outlets that would eventually operate in Philadelphia. Constraints
      included proximity restrictions (based on current ordinances regulating outlet
      distribution) of at least 200 feet between alcohol outlets and at least 300 feet
      between outlets and schools, churches, hospitals, parks and playgrounds. RESULTS:
      Findings suggest that current state policies on alcohol outlet distributions in
      Philadelphia are loosely enforced, with many areas exhibiting extremely high
      spatial densities of outlets that violate existing proximity restrictions. The
      spatial model indicates that an additional 1,115 outlets could open in
      Philadelphia if privatization was to occur and current proximity ordinances were
      maintained. CONCLUSIONS: The study reveals that spatial analytical approaches can
      function as an excellent tool for contingency-based "what-if" analysis, providing
      an objective snapshot of potential policy outcomes prior to implementation. In
      this case, the likely outcome is a tremendous increase in alcohol outlets in
      Philadelphia, with concomitant negative health, crime and quality of life
      outcomes that accompany such an increase.

PMID- 23170901
TI  - Social exclusion in childhood: a developmental intergroup perspective.
AB  - Interpersonal rejection and intergroup exclusion in childhood reflect different,
      but complementary, aspects of child development. Interpersonal rejection focuses
      on individual differences in personality traits, such as wariness and being
      fearful, to explain bully-victim relationships. In contrast, intergroup exclusion
      focuses on how in-group and out-group attitudes contribute to social exclusion
      based on group membership, such as gender, race, ethnicity, culture, and
      nationality. It is proposed that what appears to be interpersonal rejection in
      some contexts may, in fact, reflect intergroup exclusion. Whereas interpersonal
      rejection research assumes that victims invite rejection, intergroup exclusion
      research proposes that excluders reject members of out-groups to maintain status
      differences. A developmental intergroup social exclusion framework is described,
      one that focuses on social reasoning, moral judgment, and group identity.

PMID- 23170902
TI  - Looking for Candida nivariensis and C. bracarensis among a large Italian
      collection of C. glabrata isolates: results of the FIMUA working group.
AB  - Two recently described pathogenic Candida species, C. nivariensis and C.
      bracarensis, share many phenotypic characteristics with C. glabrata and are
      easily misidentified as such. The aim of this study was to determine the
      occurrence of these cryptic species in Italy. One thousand yeast isolates
      collected in 14 Italian regions and identified as C. glabrata by phenotypic and
      biochemical methods were included in this study: 928 were screened on CHROMagar
      and 72 were analysed by a multiplex PCR. None of these cryptic species was
      identified despite the nationwide distribution and the variety of biological
      origin of the isolates.

PMID- 23170900
TI  - A study of Chitosan and c-di-GMP as mucosal adjuvants for intranasal influenza
      H5N1 vaccine.
AB  - BACKGROUND: Highly pathogenic avian influenza A/H5N1 virus remains a potential
      pandemic threat, and it is essential to continue vaccine development against this
      subtype. A local mucosal immune response in the upper respiratory tract may stop
      influenza transmission. It is therefore important to develop effective intranasal
      pandemic influenza vaccines that induce mucosal immunity at the site of viral
      entry. OBJECTIVES: We evaluated the humoral and cellular immune responses of two
      promising mucosal adjuvants (Chitosan and c-di-GMP) for intranasal influenza H5N1
      vaccine in a murine model. Furthermore, we evaluated the concept of co
      adjuvanting an experimental adjuvant (c-di-GMP) with chitosan. METHODS: BALB/c
      mice were intranasally immunised with two doses of subunit NIBRG-14 (H5N1)
      vaccine (7.5, 1.5 or 0.3 MUg haemagglutinin (HA) adjuvanted with chitosan (CSN),
      c-di-GMP or both adjuvants. RESULTS: All adjuvant formulations improved the serum
      and local antibody responses, with the highest responses observed in the 7.5 MUg
      HA CSN and c-di-GMP-adjuvanted groups. The c-di-GMP provided dose sparing with
      protective single radial haemolysis (SRH), and haemagglutination inhibition (HI)
      antibody responses found in the 0.3 MUg HA group. CSN elicited a Th2 response,
      whereas c-di-GMP induced higher frequencies of virus-specific CD4+T cells
      producing one or more Th1 cytokines (IFN-gamma+, IL-2+, TNF-alpha+). A
      combination of the two adjuvants demonstrated effectiveness at 7.5 MUg HA and
      triggered a more balanced Th cytokine profile. CONCLUSION: These data show that
      combining adjuvants can modulate the Th response and in combination with ongoing
      studies of adjuvanted intranasal vaccines will dictate the way forward for
      optimal mucosal influenza vaccines.

PMID- 23170903
TI  - Effects of physical function trajectories on later long-term care utilization
      among the Taiwanese elderly.
AB  - AIM: The aim of this study was to examine the effects of trajectories of physical
      function on later long-term care utilization based on longitudinal panel data of
      older adults. METHODS: A representative longitudinal sample of older adults
      during the years 1993 to 2007 was used (n=1232). Trajectories of physical
      function from 1993 to 2007 were identified by group-based trajectory analysis,
      and then the relationships of the past trajectories with the use of nursing homes
      and care assistants, and the amount of utilization used in 2007 were examined.
      RESULTS: Four groups of physical function difficulties trajectories were
      identified: none (38.8%), little (34.1%), late increasing (16.1%) and early
      increasing (11.0%). The early- and late-increasing difficulty groups were more
      likely to use and used more nursing homes and care assistants. In particular, a
      long-term disability is closely related to a larger probability of using nursing
      homes than using care assistants at home. The utilization of care assistants
      seems a priority choice at the early-increasing stage of disability. When the
      disability worsens and lasts a long time, a nursing home is then the next choice.
      CONCLUSION: Past physical function trajectories relate to later long-term care
      utilization.

PMID- 23170904
TI  - Sulfated hyaluronan containing collagen matrices enhance cell-matrix-interaction,
      endocytosis, and osteogenic differentiation of human mesenchymal stromal cells.
AB  - Inorganic-organic composite implant materials mimicking the environment of bone
      are promising applications to meet the increasing demands on biomaterials for
      bone regeneration caused by extended life spans and the concomitant increase of
      bone treatments. Besides collagen type I (Col-I) glycosaminoglycans (GAG), such
      as hyaluronan, are important components of the bone extracellular matrix (ECM).
      Sulfated GAGs are potential stimulators of bone anabolic activity, as they are
      involved in the recruitment of mesenchymal stromal cells (MSCs) to the site of
      bone formation and support differentiation to osteoblasts. Nevertheless, no
      consecutive data is currently available about the interaction of hyaluronan or
      sulfated hyaluronan derivatives with hMSCs and the molecular processes being
      consequently regulated. We applied quantitative proteomics to investigate the
      influence of artificial ECM composed of Col-I and hyaluronan (Hya) or sulfated
      hyaluronan (HyaS3) on the molecular adaptation of osteogenic-differentiated human
      MSCs (hMSCs). Of the 1,370 quantified proteins, the expression of 4-11% was
      altered due to both aECM-combinations. Our results indicate that HyaS3 enhanced
      multiple cell functions, including cell-matrix-interaction, cell-signaling,
      endocytosis, and differentiation. In conclusion, this study provides fundamental
      insights into regulative cellular responses associated with HyaS3 and Hya as
      components of aECM and underlines the potential of HyaS3 as a promising implant
      coating-material.

PMID- 23170905
TI  - An emerging consensus on aquaporin translocation as a regulatory mechanism.
AB  - Water passes through cell membranes relatively slowly by diffusion. In order to
      maintain water homeostasis, the rapid and specific regulation of cellular water
      flow is mediated by the aquaporin (AQP) family of membrane protein water
      channels. The wide range of tissues that are known to express AQPs is reflected
      by their involvement in many physiological processes and diseases; thirteen human
      AQPs have been identified to date and the majority are highly specific for water
      while others show selectivity for water, glycerol and other small solutes.
      Receptor mediated translocation, via hormone activation, is an established method
      of AQP regulation, especially for AQP2. There is now an emerging consensus that
      the rapid and reversible translocation of other AQPs from intracellular vesicles
      to the plasma membrane, triggered by a range of stimuli, confers altered membrane
      permeability thereby acting as a regulatory mechanism. This review examines the
      molecular components that may enable such AQP regulation; these include
      cytoskeletal proteins, kinases, calcium and retention or localization signals.
      Current knowledge on the dynamic regulation of sub-cellular AQP translocation in
      response to a specific trigger is explored in the context of the regulation of
      cellular water flow.

PMID- 23170906
TI  - Between-task competition for intentions and actions.
AB  - People can switch quickly and flexibly from one task to another, but suffer the
      effects of between-task competition when they do so: After switching, they tend
      to be distracted by irrelevant stimulus information and hampered by incorrect
      actions associated with recently performed tasks. This competition results in
      performance costs of switching, as well as a bias against switching when there is
      choice over which task to perform, particularly when switching from a difficult
      task to an easier one. Two experiments investigated the locus of these between
      task competition effects in voluntary task switching. Participants switched
      between an easy location classification and a harder shape classification, making
      two responses on each trial: the first to register their task choice, the second
      to perform the chosen task on a subsequently presented stimulus. The results
      indicated that participants chose to perform the difficult shape task more often
      than the easier location task, evidence that between-task competition affects
      intentions that are expressed independently of task-specific actions. The bias
      was stronger in participants with faster choice speed, suggesting that these
      influences are relatively automatic. Moreover, even though participants had
      unlimited time to choose and prepare a task before stimulus presentation, their
      subsequent performance was nonetheless sensitive to persisting effects of between
      task competition. Altogether these results indicate the pervasive influence of
      between-task competition, which affects both the expression of global task
      intentions and the production of task-specific actions. 

PMID- 23170907
TI  - Removal of TSE agent from plasma products manufactured in the United Kingdom.
AB  - BACKGROUND AND OBJECTIVES: The outbreak of vCJD in the UK leads to concern
      regarding the potential for human-to-human transmission of this agent. Plasma
      derived products such as albumin, immunoglobulin and coagulation factors were
      manufactured by BPL from UK plasma up until 1999 when a switch to US plasma was
      made. In the current study, the capacity of various manufacturing processes that
      were in use both prior to and after this time to remove the TSE agent was tested.
      MATERIALS AND METHODS: Small-scale models of the various product manufacturing
      steps were developed. Intermediates were spiked with scrapie brain extract and
      then further processed. Samples were assayed for the abnormal form of prion
      protein (PrP(SC) ) by Western blotting, and the reduction in the amount of
      scrapie agent determined. RESULTS: Many of the manufacturing process steps
      produced significant reduction in the scrapie agent. Particularly effective were
      steps such as ethanol fractionation, depth filtration, ion-exchange and copper
      chelate affinity chromatography. Virus retentive filters, of nominal pore size 15
      or 20 nm, removed >3 log. The total cumulative reduction capacity for individual
      products was estimated to range from 7 to 14 log. In the case of factor VIII
      (8Y), the total removal was limited to 3 log. CONCLUSION: All the processes
      showed a substantial capacity to remove the TSE agent. However, this was more
      limited for the intermediate purity factor VIII 8Y which included fewer
      manufacturing steps.

PMID- 23170908
TI  - Graves' hyperthyroidism and moderate alcohol consumption: evidence for disease
      prevention.
AB  - BACKGROUND: We recently demonstrated that moderate alcohol consumption is
      associated with a considerable reduction in the risk of autoimmune
      hypothyroidism, similar to findings in other autoimmune diseases such as systemic
      lupus erythematosus and rheumatoid arthritis. We aimed to study a possible
      association between alcohol intake and autoimmune Graves' hyperthyroidism.
      DESIGN: This is a population-based, case-control study. METHODS: In a well
      defined Danish population (2,027,208 person-years of observation), we
      prospectively identified patients with new overt thyroid dysfunction and studied
      272 patients with Graves' hyperthyroidism. For each patient, we recruited four
      age-gender-region-matched controls with normal thyroid function (n = 1088).
      MEASUREMENTS: Participants gave detailed information on current and previous
      alcohol intake as well as other factors to be used for analyses. The association
      between alcohol intake and development of hyperthyroidism was analysed in
      conditional multivariate Cox regression models. RESULTS: Graves' patients had a
      lower reported alcohol consumption than controls (median units of alcohol (12 g)
      per week: 2 vs 4, P < 0.001). In a multivariate regression model, alcohol
      consumption was associated with a dose-dependent reduction in risk for
      development of overt Graves' hyperthyroidism. Odds ratios (95% confidence
      interval) compared with the reference group with a recent (last year) consumption
      of 1-2 units of alcohol per week were as follows: 0 units/week 1.73 (1.17-2.56),
      3-10 units/week 0.56 (0.39-0.79), 11-20 units/week 0.37 (0.21-0.65), >=21
      units/week 0.22 (0.08-0.60). Similar results were found for maximum previous
      alcohol consumption during a calendar year. No interaction was found with the
      type of alcohol consumed (wine vs beer), smoking habit, age, gender or region of
      inhabitancy. CONCLUSIONS: Moderate alcohol consumption is associated with a
      considerable reduction in the risk of Graves' disease with hyperthyroidism-
      irrespective of age and gender. Autoimmune thyroid disease seems to be much more
      dependent on environmental factors than hitherto anticipated.

PMID- 23170909
TI  - Repair of tracheal epithelium by basal cells after chlorine-induced injury.
AB  - BACKGROUND: Chlorine is a widely used toxic compound that is considered a
      chemical threat agent. Chlorine inhalation injures airway epithelial cells,
      leading to pulmonary abnormalities. Efficient repair of injured epithelium is
      necessary to restore normal lung structure and function. The objective of the
      current study was to characterize repair of the tracheal epithelium after acute
      chlorine injury. METHODS: C57BL/6 mice were exposed to chlorine and injected with
      5-ethynyl-2'-deoxyuridine (EdU) to label proliferating cells prior to sacrifice
      and collection of tracheas on days 2, 4, 7, and 10 after exposure. Airway repair
      and restoration of a differentiated epithelium were examined by co-localization
      of EdU labeling with markers for the three major tracheal epithelial cell types
      [keratin 5 (K5) and keratin 14 (K14) for basal cells, Clara cell secretory
      protein (CCSP) for Clara cells, and acetylated tubulin (AcTub) for ciliated
      cells]. Morphometric analysis was used to measure proliferation and restoration
      of a pseudostratified epithelium. RESULTS: Epithelial repair was fastest and most
      extensive in proximal trachea compared with middle and distal trachea. In
      unexposed mice, cell proliferation was minimal, all basal cells expressed K5, and
      K14-expressing basal cells were absent from most sections. Chlorine exposure
      resulted in the sloughing of Clara and ciliated cells from the tracheal
      epithelium. Two to four days after chlorine exposure, cell proliferation occurred
      in K5- and K14-expressing basal cells, and the number of K14 cells was
      dramatically increased. In the period of peak cell proliferation, few if any
      ciliated or Clara cells were detected in repairing trachea. Expression of
      ciliated and Clara cell markers was detected at later times (days 7-10), but cell
      proliferation was not detected in areas in which these differentiated markers
      were re-expressed. Fibrotic lesions were observed at days 7-10 primarily in
      distal trachea. CONCLUSION: The data are consistent with a model where surviving
      basal cells function as progenitor cells to repopulate the tracheal epithelium
      after chlorine injury. In areas with few remaining basal cells, repair is
      inefficient, leading to airway fibrosis. These studies establish a model for
      understanding regenerative processes in the respiratory epithelium useful for
      testing therapies for airway injury.

PMID- 23170911
TI  - Triple combination therapy to improve blood pressure control: experience with
      olmesartan-amlodipine-hydrochlorothiazide therapy.
AB  - INTRODUCTION: Effective treatment of hypertension is a key strategy for
      preventing and reducing the burden of hypertension-related cardiovascular
      diseases. In spite of these well-established concepts, hypertension remains
      poorly controlled, worldwide. Among the different pharmacological strategies
      required to improve blood pressure (BP) control, a more extensive use of
      combination therapy is progressively emerging as a cornerstone of a more
      effective treatment of hypertension. Among different drug combinations currently
      available for the clinical management of hypertension, those based on the
      association of drugs inhibiting the renin-angiotensin system, thiazide diuretics
      and calcium channel blockers have demonstrated to be very effective in lowering
      both systolic and diastolic, clinic and 24-h ambulatory BP levels with a good
      tolerability and safety profile. AREAS COVERED: In the present manuscript the
      authors provide an overview of the evidence supporting the use of triple
      combination therapy with different classes of antihypertensive drugs, with a
      particular focus on those based on olmesartan medoxomil, a thiazide diuretic
      (hydrochlorothiazide) and a calcium channel blocker (amlodipine besylate). EXPERT
      OPINION: Available data indicate that triple combination therapy based on
      olmesartan provides effective and sustained clinical and 24-h BP control in a
      high proportion of individuals among a broad range of hypertensive patients.

PMID- 23170910
TI  - Population and sex differences in Drosophila melanogaster brain gene expression.
AB  - BACKGROUND: Changes in gene regulation are thought to be crucial for the
      adaptation of organisms to their environment. Transcriptome analyses can be used
      to identify candidate genes for ecological adaptation, but can be complicated by
      variation in gene expression between tissues, sexes, or individuals. Here we use
      high-throughput RNA sequencing of a single Drosophila melanogaster tissue to
      detect brain-specific differences in gene expression between the sexes and
      between two populations, one from the ancestral species range in sub-Saharan
      Africa and one from the recently colonized species range in Europe. RESULTS:
      Relatively few genes (<100) displayed sexually dimorphic expression in the brain,
      but there was an enrichment of sex-biased genes, especially male-biased genes, on
      the X chromosome. Over 340 genes differed in brain expression between flies from
      the African and European populations, with the inter-population divergence being
      highly correlated between males and females. The differentially expressed genes
      included those involved in stress response, olfaction, and detoxification.
      Expression differences were associated with transposable element insertions at
      two genes implicated in insecticide resistance (Cyp6g1 and CHKov1). CONCLUSIONS:
      Analysis of the brain transcriptome revealed many genes differing in expression
      between populations that were not detected in previous studies using whole flies.
      There was little evidence for sex-specific regulatory adaptation in the brain, as
      most expression differences between populations were observed in both males and
      females. The enrichment of genes with sexually dimorphic expression on the X
      chromosome is consistent with dosage compensation mechanisms affecting sex-biased
      expression in somatic tissues.

PMID- 23170913
TI  - Intraurethral alprostadil for erectile dysfunction: a review of the literature.
AB  - The global burden of erectile dysfunction (ED) is increasing. It is estimated
      that 8-19% of men in Europe have ED and that by 2025 the prevalence of ED
      worldwide will reach 322 million. The gold standard therapy for ED is an oral
      phosphodiesterase type 5 (PDE5) inhibitor, but they are not suitable for
      everyone; approximately 25% of patients do not respond to this therapy and it is
      contraindicated in others, e.g. those with vascular disease. When PDE5 inhibitors
      are not suitable, available options include intraurethral and intracavernosal
      alprostadil - a synthetic vasodilator chemically identical to the naturally
      occurring prostaglandin E(1) indicated for the treatment of ED. Intraurethral
      alprostadil is delivered by the Medicated System for Erection (MUSE).- a single
      use pellet containing alprostadil suspended in polyethylene glycol administered
      using an applicator. It is recommended that intraurethral alprostadil be
      initiated at a dose of 500 MUg, as it has a higher efficacy than the 250 MUg
      dose, with minimal differences with regard to adverse events. Data from key
      clinical studies of intraurethral alprostadil show that it has a fast onset of
      effect and a good safety profile, with no occurrences of priapism, fibrosis (as
      seen with intracavernosal injection) or the typical systemic effects observed
      with oral ED pharmacological treatments. Intraurethral alprostadil has been
      associated with high patient preference, acceptance rates and quality of life
      versus intracavernosal injection due to its ease of administration. Evidence has
      shown that combination treatment with sildenafil may be a possible efficient
      alternative when single oral or local treatment has failed. Intraurethral
      alprostadil can be administered in all patients irrespective of ED origin and
      should be the first option in patients with ED for whom therapy with PDE5
      inhibitors has failed or is contraindicated.

PMID- 23170915
TI  - Ca11E3C8 (E = Sn, Pb): new complex carbide Zintl phases grown from Ca/Li flux.
AB  - New carbide Zintl phases Ca(11)E(3)C(8) (E = Sn, Pb) were grown from reactions of
      carbon and heavy tetrelides in Ca/Li flux. They form with a new structure type in
      space group P2(1)/c (a = 13.1877(9)A, b = 10.6915(7)A, c = 14.2148(9)A, beta =
      105.649(1) degrees , and R(1) = 0.019 for the Ca(11)Sn(3)C(8) analog). The
      structure features isolated E(4-) anions as well as acetylide (C(2)(2-)) and
      allenylide (C(3)(4-)) anions; the vibrational modes of the carbide anions are
      observed in the Raman spectrum. The charge-balanced nature of these phases is
      confirmed by DOS calculations which indicate that the tin analog has a small band
      gap (E(g) < 0.1 eV) and the lead analog has a pseudogap at the Fermi level.
      Reactions of these compounds with water produce acetylene and allene.

PMID- 23170914
TI  - Dapagliflozin: a review of its use in type 2 diabetes mellitus.
AB  - Dapagliflozin (Forxiga(r)) is the first in a novel class of glucose-lowering
      agents known as sodium-glucose co-transporter-2 (SGLT2) inhibitors and is used in
      the treatment of patients with type 2 diabetes. By inhibiting the transporter
      protein SGLT2 in the kidneys, dapagliflozin reduces renal glucose reabsorption,
      leading to urinary glucose excretion and a reduction in blood glucose levels.
      Unlike oral antidiabetic drugs from several other classes, the efficacy of
      dapagliflozin is independent of insulin secretion and action. Therefore, when
      used in combination with other antidiabetic drugs, dapagliflozin provides
      complementary therapy via its unique mechanism of action. A consistent finding
      across phase III, randomized, double-blind trials in patients with inadequately
      controlled type 2 diabetes was that dapagliflozin 5 or 10 mg/day for 24 weeks as
      monotherapy in previously untreated patients, or as add-on combination therapy
      with metformin, glimepiride, pioglitazone or insulin-based therapy, significantly
      reduced both glycosylated haemoglobin values (primary endpoint) and fasting
      plasma glucose levels compared with placebo. Various randomized trials have also
      shown improvements in postprandial blood glucose with dapagliflozin monotherapy
      and combination therapy compared with placebo. In addition, dapagliflozin was
      noninferior to glipizide, in terms of glycaemic control after 52 weeks, when used
      as add-on therapy in patients with type 2 diabetes that was inadequately
      controlled with metformin. In most clinical trials, dapagliflozin was associated
      with reductions in body weight that were statistically superior to placebo or
      active comparators. Longer-term extension studies indicate that the efficacy of
      dapagliflozin is maintained for up to ~2 years. Dapagliflozin was generally well
      tolerated in clinical trials of 24 or 52 weeks duration and in extension studies
      of up to ~2 years. Events suggestive of genital infections and urinary tract
      infections occurred more frequently among dapagliflozin than placebo recipients.
      These adverse events are of special interest because they appear to be related to
      the mechanism of action of dapagliflozin. Dapagliflozin has a low propensity to
      cause hypoglycaemia, especially when used alone or in combination with metformin,
      although the incidence of hypoglycaemic events reported with dapagliflozin in
      clinical trials varied depending on the background therapy. Longer-term
      tolerability/safety data with dapagliflozin are awaited with interest. In
      conclusion, dapagliflozin, with its unique and complementary mechanism of action,
      appears to be an important addition to the therapeutic options for the management
      of type 2 diabetes, particularly when used as add-on therapy.

PMID- 23170916
TI  - Sensory and consumer perception of the addition of grape seed extracts in
      cookies.
AB  - The aim of this study was to understand sensory and instrumental similarities and
      differences among an array of cookies made with bulk and microencapsulated grape
      seed extract (GSE) and then to determine how these differences impact consumer
      acceptance. Total of 4 types of cookies (control, enriched with bulk GSE, and
      enriched with 2 different microencapsulated GSE) were evaluated by instrumental
      analyses, a sensory trained panel using the quantitative descriptive analysis
      (QDA(r)) methodology, and a consumer acceptance test that included a usage and
      attitude survey. The addition of GSE resulted in darker brown cookies;
      microencapsulation partially masked the color that the GSE conferred to the
      cookies. The cookies with the microencapsulated GSE showed a significant higher
      antioxidant activity, microencapsulation may have reduced the GSE heat
      degradation. The QDA((r)) trained panelists found the enriched cookies to be more
      astringent and with aromas and flavors similar to whole grains flours. Consumers
      rated the control cookie and 1 GSE encapsulated cookie at parity; they were
      equally well liked (P > 0.05). When provided with information, nearly 60% of
      consumers stated that they were willing to purchase cookies enriched with
      antioxidants. This high positive percentage may increase if consumers received
      more education on the health benefits of antioxidant consumption.

PMID- 23170917
TI  - Spatiotemporal visualization of subcellular dynamics of carbon nanotubes.
AB  - To date, there is no consensus on the relationship between the physicochemical
      characteristics of carbon nanotubes (CNTs) and their biological behavior;
      however, there is growing evidence that the versatile characteristics make their
      biological fate largely unpredictable and remain an issue of limited knowledge.
      Here we introduce an experimental methodology for tracking and visualization of
      postuptake behavior and the intracellular fate of CNTs based on the spatial
      distribution of diffusion values throughout the plant cell. By using raster scan
      image correlation spectroscopy (RICS), we were able to generate highly
      quantitative spatial maps of CNTs diffusion in different cell compartments. The
      spatial map of diffusion values revealed that the uptake of CNTs is associated
      with important subcellular events such as carrier-mediated vacuolar transport and
      autophagy. These results show that RICS is a useful methodology to elucidate the
      intracellular behavior mechanisms of carbon nanotubes and potentially other
      fluorescently labeled nanoparticles, which is of relevance for the important
      issues related to the environmental impact and health hazards.

PMID- 23170918
TI  - Beyond the wall: Candida albicans secret(e)s to survive.
AB  - The opportunistic fungal pathogen Candida albicans occupies various niches of the
      human body such as the skin and the mucosal surfaces of the gastrointestinal and
      urogenital tracts. It can also enter the blood stream and cause deadly, systemic
      infections, especially in immunocompromised patients, but also in immunocompetent
      individuals through inserted medical devices. To survive in these diverse host
      environments, C. albicans has developed specialized virulence attributes and
      rapidly adapts itself to local growth conditions and defense mechanisms. Candida
      albicans secretes a considerable number of proteins that are involved in biofilm
      formation, tissue invasion, immune evasion, and wall maintenance, as well as
      acquisition of nutrients including metal ions. The secretome of C. albicans is
      predicted to comprise 225 proteins. On a proteomic level, however, analysis of
      the secretome of C. albicans is incomplete as many secreted proteins are only
      produced under certain conditions. Interestingly, glycosylphosphatidylinositol
      proteins and known cytoplasmic proteins are also consistently detected in the
      growth medium. Importantly, a core set of seven wall polysaccharide-processing
      enzymes seems to be consistently present, including the diagnostic marker Mp65.
      Overall, we discuss the importance of the secretome for virulence and suggest
      potential targets for better and faster diagnostic methods.

PMID- 23170919
TI  - Communication through in-person interpreters: a qualitative study of home care
      providers' and social workers' views.
AB  - AIMS AND OBJECTIVES: To describe the experiences of home care providers and
      social workers in communication, via in-person interpreters, with patients who do
      not share a common language, and to offer suggestions for practice based on this
      description. BACKGROUND: The use of interpreters is essential for successful
      communication to provide equal access to health care for patients not sharing a
      common language with care providers. Successful bilingual communication is
      probably even more complex within the home care services with its focus on
      medical treatment, care and daily support in relation to the more exclusive focus
      on medical treatment within hospital care. DESIGN: An explorative, qualitative,
      descriptive study. METHODS: Data were collected in seven focus group interviews.
      A total of 27 persons, working as registered nurses, assistant nurses and social
      workers in municipal home care, participated. The analysis was inspired by
      inductive content analysis. RESULTS: The results express a traditional view on
      interpretation where the in-person interpreter is supposed to act to a greater or
      lesser extent as an objective and neutral conduit or communicator of what is
      said. The interpreter is also expected to observe when medical terms and other
      concepts need to be explained, which thus exceeds the basic role as a
      communicator of what was said. CONCLUSIONS: This study emphasises the need to
      view the interpreter as an active and explicit party in a three-way
      communication. RELEVANCE TO CLINICAL PRACTICE: Viewing the interpreter as an
      active and explicit party in a three-way communication and as an essential part
      of the care team might reduce the possible threat to patient confidentiality, and
      could contribute to solve the problem of interpreting the patient's non-verbal
      signs.

PMID- 23170920
TI  - Occurrence and reduction of human viruses, F-specific RNA coliphage genogroups
      and microbial indicators at a full-scale wastewater treatment plant in Japan.
AB  - AIMS: To evaluate and compare the reductions of human viruses and F-specific
      coliphages in a full-scale wastewater treatment plant based on the quantitative
      PCR (qPCR) and plate count assays. METHODS AND RESULTS: A total of 24 water
      samples were collected from four locations at the plant, and the relative
      abundance of human viruses and F-RNA phage genogroups were determined by qPCR. Of
      the 10 types of viruses tested, enteric adenoviruses were the most prevalent in
      both influent and effluent wastewater samples. Of the different treatment steps,
      the activated sludge process was most effective in reducing the microbial loads.
      Viruses and F-RNA phages showed variable reduction; among them, GI and GIII F-RNA
      phages showed the lowest and the highest reduction, respectively. CONCLUSIONS:
      Ten types of viruses were present in wastewater that is discharged into public
      water bodies after treatment. The variability in reduction for the different
      virus types demonstrates that selection of adequate viral indicators is important
      for evaluating the efficacy of wastewater treatment and ensuring the water
      safety. SIGNIFICANCE AND IMPACT OF THE STUDY: Our comprehensive analyses of the
      occurrence and reduction of viruses and indicators can contribute to the future
      establishment of appropriate viral indicators to evaluate the efficacy of
      wastewater treatment.

PMID- 23170921
TI  - Comparison between the recovery time of alfentanil and fentanyl in balanced
      propofol sedation for gastrointestinal and colonoscopy: a prospective, randomized
      study.
AB  - BACKGROUND: There is increasing interest in balanced propofol sedation (BPS)
      titrated to moderate sedation (conscious sedation) for endoscopic procedures.
      However, few controlled studies on BPS targeted to deep sedation for diagnostic
      endoscopy were found. Alfentanil, a rapid and short-acting synthetic analog of
      fentanyl, appears to offer clinically significant advantages over fentanyl during
      outpatient anesthesia.It is reasonable to hypothesize that low dose of alfentanil
      used in BPS might also result in more rapid recovery as compared with fentanyl.
      METHODS: A prospective, randomized and double-blinded clinical trial of
      alfentanil, midazolam and propofol versus fentanyl, midazolam and propofol in 272
      outpatients undergoing diagnostic esophagogastroduodenal endoscopy (EGD) and
      colonoscopy for health examination were enrolled. Randomization was achieved by
      using the computer-generated random sequence. Each combination regimen was
      titrated to deep sedation. The recovery time, patient satisfaction, safety and
      the efficacy and cost benefit between groups were compared. RESULTS: 260
      participants were analyzed, 129 in alfentanil group and 131 in fentanyl group.
      There is no significant difference in sex, age, body weight, BMI and ASA
      distribution between two groups. Also, there is no significant difference in
      recovery time, satisfaction score from patients, propofol consumption, awake time
      from sedation, and sedation-related cardiopulmonary complications between two
      groups. Though deep sedation was targeted, all cardiopulmonary complications were
      minor and transient (10.8%, 28/260). No serious adverse events including the use
      of flumazenil, assisted ventilation, permanent injury or death, and temporary or
      permanent interruption of procedure were found in both groups. However, fentanyl
      is New Taiwan Dollar (NT$) 103 (approximate US$ 4) cheaper than alfentanil,
      leading to a significant difference in total cost between two groups.
      CONCLUSIONS: This randomized, double-blinded clinical trial showed that there is
      no significant difference in the recovery time, satisfaction score from patients,
      propofol consumption, awake time from sedation, and sedation-related
      cardiopulmonary complications between the two most common sedation regimens for
      EGD and colonoscopy in our hospital. However, fentanyl is NT$103 (US$ 4) cheaper
      than alfentanil in each case. TRIAL REGISTRATION: Institutional Review Board of
      Buddhist Tzu Chi General Hospital (IRB097-18) and Chinese Clinical Trial Registry
      (ChiCTR-TRC-12002575).

PMID- 23170922
TI  - An individual urinary proteome analysis in normal human beings to define the
      minimal sample number to represent the normal urinary proteome.
AB  - BACKGROUND: The urinary proteome has been widely used for biomarker discovery. A
      urinary proteome database from normal humans can provide a background for
      discovery proteomics and candidate proteins/peptides for targeted proteomics.
      Therefore, it is necessary to define the minimum number of individuals required
      for sampling to represent the normal urinary proteome. METHODS: In this study,
      inter-individual and inter-gender variations of urinary proteome were taken into
      consideration to achieve a representative database. An individual analysis was
      performed on overnight urine samples from 20 normal volunteers (10 males and 10
      females) by 1DLC/MS/MS. To obtain a representative result of each sample, a
      replicate 1DLCMS/MS analysis was performed. The minimal sample number was
      estimated by statistical analysis. RESULTS: For qualitative analysis, less than
      5% of new proteins/peptides were identified in a male/female normal group by
      adding a new sample when the sample number exceeded nine. In addition, in a
      normal group, the percentage of newly identified proteins/peptides was less than
      5% upon adding a new sample when the sample number reached 10. Furthermore, a
      statistical analysis indicated that urinary proteomes from normal males and
      females showed different patterns. For quantitative analysis, the variation of
      protein abundance was defined by spectrum count and western blotting methods. And
      then the minimal sample number for quantitative proteomic analysis was
      identified. CONCLUSIONS: For qualitative analysis, when considering the inter
      individual and inter-gender variations, the minimum sample number is 10 and
      requires a balanced number of males and females in order to obtain a
      representative normal human urinary proteome. For quantitative analysis, the
      minimal sample number is much greater than that for qualitative analysis and
      depends on the experimental methods used for quantification.

PMID- 23170923
TI  - A puzzling and rare cause of chest and shoulder pain: migrated foreign body to
      the spleen.

PMID- 23170924
TI  - Use of medical tourism for hip and knee surgery in osteoarthritis: a qualitative
      examination of distinctive attitudinal characteristics among Canadian patients.
AB  - BACKGROUND: Medical tourism is the term that describes patients' international
      travel with the intention of seeking medical treatment. Some medical tourists go
      abroad for orthopaedic surgeries, including hip and knee resurfacing and
      replacement. In this article we examine the findings of interviews with Canadian
      medical tourists who went abroad for such surgeries to determine what is
      distinctive about their attitudes when compared to existing qualitative research
      findings about patients' decision-making in and experiences of these same
      procedures in their home countries. METHODS: Fourteen Canadian medical tourists
      participated in semi-structured phone interviews, all of whom had gone abroad for
      hip or knee surgery to treat osteoarthritis. Transcripts were coded and
      thematically analysed, which involved comparing emerging findings to those in the
      existing qualitative literature on hip and knee surgery. RESULTS: Three
      distinctive attitudinal characteristics among participants were identified when
      interview themes were compared to findings in the existing qualitative research
      on hip and knee surgery in osteoarthritis. These attitudinal characteristics were
      that the medical tourists we spoke with were: (1) comfortable health-related
      decision-makers; (2) unwavering in their views about procedure necessity and
      urgency; and (3) firm in their desires to maintain active lives. CONCLUSIONS:
      Compared to other patients reported on in the existing qualitative hip and knee
      surgery literature, medical tourists are less likely to question their need for
      surgery and are particularly active in their pursuit of surgical intervention.
      They are also comfortable with taking control of health-related decisions. Future
      research is needed to identify motivators behind patients' pursuit of care
      abroad, determine if the attitudinal characteristics identified here hold true
      for other patient groups, and ascertain the impact of these attitudinal
      characteristics on surgical outcomes. Arthritis care providers can use the
      attitudinal characteristics identified here to better advise osteoarthritis
      patients who are considering seeking care abroad.

PMID- 23170926
TI  - Melatonin treatment at dry-off improves reproductive performance postpartum in
      high-producing dairy cows under heat stress conditions.
AB  - CONTENTS: The aim of this study was to determine the effect of melatonin
      treatment during the early dry-off period on subsequent reproductive performance
      and milk production in high-producing dairy cows under heat stress conditions. In
      experiment I, addressing the pharmacokinetics of melatonin treatment in lactating
      dairy cows, doses of untreated, 3, 6, 9 or 12 implants/animal (18-mg melatonin
      each implant) were given as subcutaneous implants on gestation day 120-20
      multiparous lactating dairy cows (four cows/dose group). Experiment II was
      performed during the warm season on 25 heifers and 114 high milk-producing
      Holstein-Friesian cows. Animals were randomly assigned to a control (C) or
      melatonin group (M). Animals in the M group received nine implants (heifers) or
      12 (cows) of melatonin on day 220 of gestation. In experiment I, cows in the 12
      implants group showed a higher maximum melatonin concentration (Cmax ) and area
      under the concentration curve from treatment day 0 to day 49 (AUC0-49d ) than
      those in the remaining groups, among which there were no significant differences
      in this variable. In experiment II, the likelihood of repeat breeding syndrome
      (<3 vs >=4 AIs per cow) and pregnancy loss (first trimester) were 0.36 and 0.19
      times lower in treated than control animals, respectively. Plasma prolactin
      levels decreased significantly (p = 0.01) after melatonin treatment and recovered
      during the postpartum compared to control cows. No significant effects on milk
      production were observed in the subsequent lactation. Significant differences in
      days open between groups (means 123 +/- 71.9 and 103 +/- 43, respectively, for C
      and M; p = 0.02) were registered. In conclusion, melatonin treatment in the early
      dry-off period improves the reproductive performance of dairy cattle, reducing
      the number of days open, repeat breeding syndrome and pregnancy loss.

PMID- 23170925
TI  - PTPRZ1 regulates calmodulin phosphorylation and tumor progression in small-cell
      lung carcinoma.
AB  - BACKGROUND: Small-cell lung carcinoma (SCLC) is a neuroendocrine tumor subtype
      and comprises approximately 15% of lung cancers. Because SCLC is still a disease
      with a poor prognosis and limited treatment options, there is an urgent need to
      develop targeted molecular agents for this disease. METHODS: We screened 20 cell
      lines from a variety of pathological phenotypes established from different organs
      by RT-PCR. Paraffin-embedded tissue from 252 primary tumors was examined for
      PTPRZ1 expression using immunohistochemistry. shRNA mediated PTPRZ1 down
      regulation was used to study impact on tyrosine phosphorylation and in vivo tumor
      progression in SCLC cell lines. RESULTS: Here we show that PTPRZ1, a member of
      the protein tyrosine- phosphatase receptor (PTPR) family, is highly expressed in
      SCLC cell lines and specifically exists in human neuroendocrine tumor (NET)
      tissues. We also demonstrate that binding of the ligand of PTPRZ1, pleiotrophin
      (PTN), activates the PTN/PTPRZ1 signaling pathway to induce tyrosine
      phosphorylation of calmodulin (CaM) in SCLC cells, suggesting that PTPRZ1 is a
      regulator of tyrosine phosphorylation in SCLC cells. Furthermore, we found that
      PTPRZ1 actually has an important oncogenic role in tumor progression in the
      murine xenograft model. CONCLUSION: PTPRZ1 was highly expressed in human NET
      tissues and PTPRZ1 is an oncogenic tyrosine phosphatase in SCLCs. These results
      imply that a new signaling pathway involving PTPRZ1 could be a feasible target
      for treatment of NETs.

PMID- 23170927
TI  - Home visitation program effectiveness and the influence of community behavioral
      norms: a propensity score matched analysis of prenatal smoking cessation.
AB  - BACKGROUND: The influence of community context on the effectiveness of evidence
      based maternal and child home visitation programs following implementation is
      poorly understood. This study compared prenatal smoking cessation between home
      visitation program recipients and local-area comparison women across 24
      implementation sites within one state, while also estimating the independent
      effect of community smoking norms on smoking cessation behavior. METHODS:
      Retrospective cohort design using propensity score matching of Nurse-Family
      Partnership (NFP) clients and local-area matched comparison women who smoked
      cigarettes in the first trimester of pregnancy. Birth certificate data were used
      to classify smoking status. The main outcome measure was smoking cessation in the
      third trimester of pregnancy. Multivariable logistic regression analysis
      examined, over two time periods, the association of NFP exposure and the
      association of baseline county prenatal smoking rate on prenatal smoking
      cessation. RESULTS: The association of NFP participation and prenatal smoking
      cessation was stronger in a later implementation period (35.5% for NFP clients
      vs. 27.5% for comparison women, p < 0.001) than in an earlier implementation
      period (28.4% vs. 25.8%, p = 0.114). Cessation was also negatively associated
      with county prenatal smoking rate, controlling for NFP program effect, (OR = 0.84
      per 5 percentage point change in county smoking rate, p = 0.002). CONCLUSIONS:
      Following a statewide implementation, program recipients of NFP demonstrated
      increased smoking cessation compared to comparison women, with a stronger program
      effect in later years. The significant association of county smoking rate with
      cessation suggests that community behavioral norms may present a challenge for
      evidence-based programs as models are translated into diverse communities.

PMID- 23170928
TI  - Role of the saturated nonesterified fatty acid palmitate in beta cell
      dysfunction.
AB  - Sustained elevated levels of saturated free fatty acids, such as palmitate,
      contribute to beta cell dysfunction, a phenomenon aggravated by high glucose
      levels. The aim of this study was to investigate the mechanisms of palmitate
      induced beta cell dysfunction and death, combined or not with high glucose.
      Protein profiling of INS-1E cells, exposed to 0.5 mmol/L palmitate and combined
      or not with 25 mmol/L glucose, for 24 h was done by 2D-DIGE, both on full cell
      lysate and on an enriched endoplasmic reticulum (ER) fraction. Eighty-three
      differentially expressed proteins (P < 0.05) were identified by MALDI-TOF/TOF
      mass spectrometry and proteomic results were confirmed by functional assays. 2D
      DIGE analysis of whole cell lysates and ER enriched samples revealed a high
      number of proteins compared to previous reports. Palmitate induced beta cell
      dysfunction and death via ER stress, hampered insulin maturation, generation of
      harmful metabolites during triglycerides synthesis and altered intracellular
      trafficking. In combination with high glucose, palmitate induced increased
      shunting of excess glucose, increased mitochondrial reactive oxygen species
      production and an elevation in many transcription-related proteins. This study
      contributes to a better understanding and revealed novel mechanisms of palmitate
      induced beta cell dysfunction and death and may provide new targets for drug
      discovery.

PMID- 23170929
TI  - Laparoscopic splenectomy with or without devascularization of the stomach for
      liver cirrhosis and portal hypertension: a systematic review.
AB  - BACKGROUND: Open splenectomy and devascularization are effective treatments for
      cirrhotic patients with severe thrombocytopenia and variceal bleeding. However,
      it remains controversial whether laparoscopic splenectomy (LS) and
      devascularization (LSD) can be indicated and beneficial in these patients.
      OBJECTIVES: A systematic review of the efficacy and safety of LS and LSD for
      patients with liver cirrhosis and portal hypertension was undertaken to clarify
      controversy about their utilization in such patients. METHODS: A systematic
      search strategy was performed to retrieve relevant studies from PubMed and
      Embase.com. The literature search and data extraction were independently
      performed by two reviewers. RESULTS: Sixteen articles met the inclusion criteria.
      The methodology of the identified articles was poor. Six hundred and fifty-one
      patients, including 478 LS patients and 173 LSD patients, were involved in
      efficacy and safety evaluations. There was wide variability in the outcome
      measures between studies. There was only one death in the patients underwent LSD.
      Reported major complications included post-operative bleeding requiring re
      surgery, pancreatic leakage and gastric perforation. Seven studies were
      identified with comparisons between laparoscopic and open procedures. No meta
      analysis was possible because of heterogeneity between studies and lack of
      randomization. CONCLUSIONS: The publications reviewed revealed LS and LSD to be
      safe and effective in the setting of liver cirrhosis and portal hypertension.
      From the comparison articles, laparoscopic procedures appear to be superior to
      open procedures regarding blood loss, hospital stay, complication rate and liver
      function impairment. However, it is difficult to draw firm statistical
      conclusions due to lack of high-quality evidence.

PMID- 23170930
TI  - The effect of docosahexaenoic acid on t10, c12-conjugated linoleic acid-induced
      changes in fatty acid composition of mouse liver, adipose, and muscle.
AB  - BACKGROUND: Concomitant supplementation of 1.5% docosahexaenoic acid (22:6 n-3;
      DHA) with 0.5% t10, c12-conjugated linoleic acid (18:2 n-6; CLA) prevented the
      CLA-induced increase in expression of hepatic genes involved in fatty acid
      synthesis and the decrease in expression of genes involved in fatty acid
      oxidation. The effect of CLA on fatty acid compositions of adipose tissue and
      muscle and whether DHA can prevent those CLA-induced changes in fatty acid
      composition is not known. METHODS: We investigated if DHA fed concomitantly with
      CLA for 4 weeks will prevent the CLA-induced changes in fatty acid compositions
      of liver, adipose, and muscle lipids in C57BL/6N female mice. We also examined
      changes in expression of adipose tissue genes involved in fatty acid synthesis,
      oxidation, uptake, and lipolysis. RESULTS: CLA supplementation increased liver
      fat and decreased total n-3 polyunsaturated fat (PUFA) concentration. DHA not
      only prevented the CLA-induced changes in liver fat, but also increased n-3 PUFA
      by >350% as compared with the control group. CLA decreased adipose weight and the
      expression of genes involved in fatty acid synthesis, oxidation, and uptake and
      increased that of uncoupling protein 2 (UCP2). Supplementing DHA along with CLA
      increased adipose n-3 PUFA by >1000% compared with control group, but did not
      prevent the CLA-induced changes in mass or gene expression. Both CLA and DHA were
      incorporated into muscle lipids, but had minor effects on fatty acid composition.
      CONCLUSIONS: Liver, adipose tissue, and muscle responded differently to CLA and
      DHA supplementation. DHA prevented CLA-induced increase in liver fat but not loss
      of adipose mass.

PMID- 23170931
TI  - Colesevelam plus rosuvastatin 5 mg/day versus rosuvastatin 10 mg/day alone on
      markers of insulin resistance in patients with hypercholesterolemia and impaired
      fasting glucose.
AB  - BACKGROUND: Statin use has been associated with adverse effects on insulin
      sensitivity and the development of new-onset diabetes. Colesevelam exhibits
      favorable effects on glucose metabolism. It is not known whether the combination
      of colesevelam plus low-dose statin has different effects on insulin resistance
      versus higher-dose statin in patients with impaired fasting glucose (IFG) and
      hypercholesterolemia. METHODS: This was a prospective randomized open-label
      blinded end point (PROBE) study. Forty patients with hypercholesterolemia and IFG
      were randomized to receive rosuvastatin 5 mg/day plus colesevelam 3.75 g/day (RC,
      n=20) or rosuvastatin 10 mg (R, n=20) for 3 months. The primary end point was the
      difference in the change of homeostasis model assessment of insulin resistance
      (HOMA-IR) index between the groups. RESULTS: HOMA-IR index significantly
      decreased in the RC group (-32%, P=0.04 vs. baseline) but nonsignificantly
      increased (+15%, P=NS) in the R group. Insulin levels decreased in the RC group (
      26%, P=NS) but increased in the R group (+15%, P=NS). Both changes in HOMA-IR and
      insulin differed significantly between groups (both p<0.05). Glucose levels
      decreased in the RC group (-5%, P=NS), whereas they remained unaltered in the R
      group. Similar reductions in low-density lipoprotein cholesterol were observed in
      both groups (-45%; P<0.001 vs. baseline). Triglycerides remained unchanged in the
      RC group but decreased in the R group (-24%, P<0.001 vs. baseline and P=0.02 vs.
      RC group). CONCLUSIONS: The combination of colesevelam with rosuvastatin 5 mg/day
      may be associated with favorable effects on markers of insulin resistance
      compared with rosuvastatin 10 mg/day in patients with hypercholesterolemia and
      IFG. Whether this is associated with less new-onset diabetes remains unknown.

PMID- 23170932
TI  - Major histocompatibility complex class-II molecules promote targeting of human
      immunodeficiency virus type 1 virions in late endosomes by enhancing
      internalization of nascent particles from the plasma membrane.
AB  - Productive assembly of human immunodeficiency virus type 1 (HIV-1) takes place,
      primarily, at the plasma membrane. However, depending on the cell types, a
      significant proportion of nascent virus particles are internalized and routed to
      late endosomes. We previously reported that expression of human leucocyte antigen
      (HLA)-DR promoted a redistribution of Gag in late endosomes and an increased
      detection of mature virions in these compartments in HeLa and human embryonic
      kidney 293T model cell lines. Although this redistribution of Gag resulted in a
      marked decrease of HIV-1 release, the underlying mechanism remained undefined.
      Here, we provide evidence that expression of HLA-DR at the cell surface induces a
      redistribution of mature Gag products into late endosomes by enhancing nascent
      HIV-1 particle internalization from the plasma membrane through a process that
      relies on the presence of intact HLA-DR alpha and beta-chain cytosolic tails.
      These findings raise the possibility that major histocompatibility complex class
      II molecules might influence endocytic events at the plasma membrane and as a
      result promote endocytosis of progeny HIV-1 particles.

PMID- 23170933
TI  - Children's cross-ethnic relationships in elementary schools: concurrent and
      prospective associations between ethnic segregation and social status.
AB  - This study examined whether ethnic segregation is concurrently (fall) and
      prospectively (fall to spring) associated with social status among 4th- and 5th
      grade African American and European American children (n = 713, ages 9-11 years).
      Segregation measures were (a) same-ethnicity favoritism in peer affiliations and
      (b) cross-ethnicity dislike. Social status measures were same- and cross
      ethnicity peer nominations of acceptance, rejection, and cool. Among African
      Americans, fall segregation predicted declines in cross-ethnicity (European
      American) acceptance and same-ethnicity rejection, and increases in same
      ethnicity acceptance and perceived coolness. For European American children, fall
      segregation predicted declines in cross-ethnicity (African American) acceptance
      and increases in cross-ethnicity rejection. Results indicate that segregation
      induces asymmetric changes in social status for African American and European
      American children.

PMID- 23170934
TI  - The genetics of alcohol dependence.
AB  - Alcohol consumption dates back to the Neolithic period, and alcohol dependence
      contributes substantially to the current global burden of disease. Despite this,
      optimal therapies and preventive strategies are lacking. Formal genetic studies
      of alcohol dependence have shown that genetic factors play as large a role in
      disease etiology as environmental factors. Molecular genetic studies may identify
      causal factors and facilitate the development of novel preventive and therapeutic
      approaches. Whereas earlier studies involved the use of linkage- and candidate
      gene approaches, recent years have witnessed the introduction of genome-wide
      association studies (GWAS). The present review provides a brief overview of the
      findings of formal genetic studies, summarizes the results of earlier molecular
      genetic investigations, and presents a detailed overview of all published GWAS in
      the field of alcohol dependence research. To date, few genome-wide significant
      findings have been reported. However, through the polygenic approach, GWAS have
      both confirmed the existence of a multitude of novel risk genes and indicated
      interesting new candidates.

PMID- 23170935
TI  - Scaling of upper-body power output to predict time-trial roller skiing
      performance.
AB  - The purpose of the present study was to establish the most appropriate allometric
      model to predict mean skiing speed during a double-poling roller skiing time
      trial using scaling of upper-body power output. Forty-five Swedish junior cross
      country skiers (27 men and 18 women) of national and international standard were
      examined. The skiers, who had a body mass (m) of 69.3 +/- 8.0 kg (mean +/- s),
      completed a 120-s double-poling test on a ski ergometer to determine their mean
      upper-body power output (W). Performance data were subsequently obtained from a 2
      km time-trial, using the double-poling technique, to establish mean roller skiing
      speed. A proportional allometric model was used to predict skiing speed. The
      optimal model was found to be: Skiing speed = 1.057 . W (0.556) . m (-0.315),
      which explained 58.8% of the variance in mean skiing speed (P < 0.001). The 95%
      confidence intervals for the scaling factors ranged from 0.391 to 0.721 for W and
      from -0.626 to -0.004 for m. The results in this study suggest that allometric
      scaling of upper-body power output is preferable for the prediction of
      performance of junior cross-country skiers rather than absolute expression or
      simple ratio-standard scaling of upper-body power output.

PMID- 23170936
TI  - Increased circulating CC chemokine levels in the metabolic syndrome are reduced
      by low-dose atorvastatin treatment: evidence from a randomized controlled trial.
AB  - OBJECTIVE: Central obesity and insulin resistance are key components of the
      metabolic syndrome, which is associated with an increased risk of cardiovascular
      disease. In obesity, CC chemokines, such as monocyte chemotactic protein-1 (MCP
      1), macrophage inhibitory protein-1beta (MIP-1beta) and eotaxin-1 and their
      respective receptors, are critically involved in peripheral monocyte activation
      and adipose tissue infiltration. The aim of the current study was to examine
      whether low-dose atorvastatin (10 mg/d) treatment modulated serum levels of CC
      chemokines in metabolic syndrome subjects. MATERIALS AND METHODS: Serum levels of
      MCP-1, eotaxin-1, MIP-1beta, C reactive protein (CRP) and interleukin-6 (IL-6)
      were measured in lean control and metabolic syndrome subjects at baseline, and
      following a 6-week randomized placebo-controlled clinical trial of atorvastatin
      (10 mg/d). Peripheral CD14(+) monocytes were isolated and mRNA levels of MCP-1,
      MIP-1 beta and CCR5 determined. RESULTS: Serum MCP-1 (P = 0.02), eotaxin-1 (P =
      0.02) and MIP-1beta (P = 0.03), CRP (P < 0.001) and IL-6 (P = 0.006) were
      significantly increased in metabolic syndrome in comparison with lean controls.
      Furthermore, CD14(+) peripheral monocyte mRNA expression of the chemokine
      receptor, CCR5, of which MIP-1beta and eotaxin-1 are ligands, was increased two
      fold in the metabolic syndrome group (P = 0.03). In addition to the expected
      improvements in lipid profile, atorvastatin treatment significantly reduced
      circulating eotaxin-1 (P < 0.05), MIP-1beta (P < 0.05) levels and CD14(+)
      peripheral monocyte CCR5 mRNA expression (P = 0.02). CONCLUSION: These results
      support a model whereby atorvastatin treatment, by inhibiting CD14(+) monocyte
      CCR5 expression, may inhibit monocyte trafficking, reduce chronic inflammation
      and, thus, lower circulating levels of CC chemokines.

PMID- 23170937
TI  - Arg188 in rice sucrose transporter OsSUT1 is crucial for substrate transport.
AB  - BACKGROUND: Plant sucrose uptake transporters (SUTs) are H+/sucrose symporters
      related to the major facilitator superfamily (MFS). SUTs are essential for plant
      growth but little is known about their transport mechanism. Recent work
      identified several conserved, charged amino acids within transmembrane spans
      (TMS) in SUTs that are essential for transport activity. Here we further
      evaluated the role of one of these positions, R188 in the fourth TMS of OsSUT1, a
      type II SUT. RESULTS: The OsSUT1(R188K) mutant, studied by expression in plants,
      yeast, and Xenopus oocytes, did not transport sucrose but showed a H+ leak that
      was blocked by sucrose. The H+ leak was also blocked by beta-phenyl glucoside
      which is not translocated by OsSUT1. Replacing the corresponding Arg in type I
      and type III SUTs, AtSUC1(R163K) and LjSUT4(R169K), respectively, also resulted
      in loss of sucrose transport activity. Fluorination at the glucosyl 3 and 4
      positions of alpha-phenyl glucoside greatly decreased transport by wild type
      OsSUT1 but did not affect the ability to block H+ leak in the R188K mutant.
      CONCLUSION: OsSUT1 R188 appears to be essential for sucrose translocation but not
      for substrate interaction that blocks H+ leak. Therefore, we propose that an
      additional binding site functions in the initial recognition of substrates. The
      corresponding Arg in type I and III SUTs are equally important. We propose that
      R188 interacts with glucosyl 3-OH and 4-OH during translocation.

PMID- 23170938
TI  - Candesartan plus hydrochlorothiazide: an overview of its use and efficacy.
AB  - INTRODUCTION: The 2007 European Society of Cardiology/ European Society of
      Hypertension guidelines suggests that among the therapeutic possibilities, the
      use of angiotensin receptor blockers as an important component of
      antihypertensive combination therapy. Thiazide-type diuretics are usually added
      in order to increase the therapeutic efficacy in lowering blood pressure (BP).
      Many authors have demonstrated how effective is a fixed-dose combination of
      candesartan cilexetil/hydrochlorothiazide in lowering BP, even when compared with
      other antihypertensive drugs belonging to the same therapeutic category.
      Moreover, this combination showed good compliance and tolerability and few
      adverse reactions. AREAS COVERED: The authors analyze the importance of the
      combination therapy of candesartan cilexetil plus hydrochlorothiazide in the
      treatment of hypertension. Many authors explain how effective BP control is often
      achieved only with the combination of drugs with different mechanisms of action,
      in particular in high risk patients or in those affected with diabetes mellitus
      or chronic renal disease; in fact, these patients need a more intensive BP
      control. EXPERT OPINION: The fixed-dose combination drug
      candesartan/hydrochlorothiazide turned out to be a significant alternative in the
      treatment of hypertension, both for its high efficacy in BP reduction and in
      prevention of target organ damage, both for its tolerability and patient
      compliance.

PMID- 23170940
TI  - Comparison of otoplasty results using different types of suturing techniques.
AB  - BACKGROUND: Prominent ears are a common congenital deformity. Numerous techniques
      have been developed for the treatment of protruding ears, indicating that there
      is no single widely-accepted procedure. Modern otoplasty techniques fall into of
      two main surgical categories, (1) cartilage sparing (Mustarde & Furnas), and (2)
      cartilage cutting (Chongchet & Stenstrom). This study compares an
      antihelixmastoid suture technique with the normal Mustarde & Furnas technique.
      METHODS: Within a 5-year period (between 2005 and 2009), 78 patients (mean age 27
      years; range 7 to 46) underwent otoplasty performed by the senior author (in a
      private plastic surgery center), employing the posterior suturing technique
      (Mustarde & Furnas). Of these 78 patients, 44 underwent otoplasty which combined
      the usual posterior suturing technique with modification we have developed
      (antihelixmastoid sutures). Depending on the suture technique used, the patients
      were divided into two groups: Group 1 (Mustarde & Furnas sutures), Group 2
      (Mustarde & Furnas sutures with extra modification). Patients were invited for
      follow-up examinations 1 month and 1 year after surgery, and all of them attended
      both these follow-up checks, where recurrence and suture extrusion were
      evaluated. RESULTS: Group 1: the clinical recurrence rate was 4.55% (3 ears). The
      suture extrusion rate was 7.6% (5 ears). Group 2: the clinical recurrence rate
      was 1.25% (1 ear). The suture extrusion rate was 7.5% (6 ears). Patients were
      generally satisfied with the results in terms of shape and symmetry. There were
      no complications such as haematoma, ear deformity and skin necrosis. CONCLUSIONS:
      Posterior suturing with conchomastoid and modification of Mustarde sutures is a
      simple operation which can be performed quickly. It appears to be effective in
      terms of recurrence rate (especially in the upper segment) and patient
      satisfaction.

PMID- 23170939
TI  - Decreased miR-192 expression in peripheral blood of asthmatic individuals
      undergoing an allergen inhalation challenge.
AB  - BACKGROUND: MicroRNAs are small non-coding RNAs that regulate gene expression at
      the post-transcriptional level. While they have been implicated in various
      diseases, the profile changes in allergen inhalation challenge are not clarified
      in human. We aimed to evaluate changes in the microRNA profiles in the peripheral
      blood of asthmatic subjects undergoing allergen inhalation challenge. RESULTS:
      Seven mild asthmatic subjects participated in the allergen inhalation challenge.
      In addition, four healthy control subjects (HCs) were recruited. MicroRNA
      profiles in peripheral blood samples (pre-challenge and 2 hours post-challenge)
      were measured by the NanoString nCounter assay to determine changes in miRNA
      levels as these asthmatic subjects underwent an allergen inhalation challenge.
      One common miRNA, miR-192, was significantly expressed in both comparisons; HCs
      vs. pre-challenge and pre- vs. post-challenge, showing that miR-192 was
      significantly under-expressed in asthmatics compared to HCs and decreased in post
      challenge at an FDR of 1%. Cell-specific statistical deconvolution attributed miR
      192 expression in whole blood to PBMCs. MiR-192 was technically validated using
      real-time reverse transcription-quantitative polymerase chain reaction (RT-qPCR)
      showing that the level in asthmatics (pre-challenge) was significantly lower than
      HCs and that post-challenge was significantly lower than pre-challenge. The
      normalized relative miR-192 expression quantified using RT-qPCR specific to PBMCs
      was also validated. Ontology enrichment and canonical pathway analyses for target
      genes suggested several functions and pathways involved in immune response and
      cell cycle. CONCLUSIONS: The miRNA profile in peripheral blood was altered after
      allergen inhalation challenge. Change in miR-192 levels may be implicated in
      asthma mechanisms. These results suggest that allergen inhalation challenge is a
      suitable method to characterize peripheral miRNA profiles and potentially
      elucidate the mechanism of human asthma.

PMID- 23170941
TI  - Breast hypertrophy and asymmetry: a retrospective study on a sample of 344
      consecutive patients.
AB  - BACKGROUND: Preoperative evaluation of the anatomical features of the region
      around the breast is strongly recommended in order to choose the most appropriate
      technique of reductive mammaplasty. Normally breast hypertrophy presents itself
      as a bilateral clinical picture, but no study in the literature refers to the
      incidence of volumetric asymmetry. AIMS: This study aims to analyze weight
      differences between the right and left breast on a selected sample of patients
      who underwent reductive mammaplasty or mastopexy over the last five years at our
      Plastic Surgery Unit and have maintained a good postoperative symmetry for at
      least 1 year subsequently. PATIENTS AND METHOD: 344 consecutive cases treated
      between January 2005 and April 2010 were considered for this study. Patients were
      classified according to the degree of hypertrophy and age. Breast asymmetry was
      scored, according to the senior author's original classification, on the weight
      difference of glandular resection. RESULTS AND CONCLUSION: In 20% of the patients
      a difference greater than 200 g was found. The statistical analysis showed no
      significant differences in the predominant side (left or right). Breast
      hypertrophy is confirmed as a substantially bilateral pathology, but in 1 out of
      5 patients a difference of more than one quadrant can be present: thus a careful
      evaluation is essential in order to decide the correct surgical strategy.

PMID- 23170942
TI  - Reconstruction of the hand in Apert syndrome: two case reports and a literature
      review of updated strategies for diagnosis and management.
AB  - BACKGROUND: Apert syndrome is a set of complex malformations of the first
      brachial arch, with manifestations on the skull, face, hands and feet. At the
      level of the hand, the following signs are always present: complex syndactyly of
      the second, third and fourth digits with distal bone fusion; simple syndactyly of
      the fifth digit; foreshortened thumb with radial clinodactily; and symphalangism
      excluding the fifth digit. METHODS: The digital separation of an Apert hand
      should begin at 9 months of age and should be completed by 2 to 4 years of age.
      Our simplified approach consists of early bilateral surgery on border digits
      followed by unilateral separation of middle syndactily combined with thumb and
      digit osteotomies and bone grafting as required. RESULTS: Between 1995 and 2010
      seven patients with Apert syndrome underwent reconstructive surgery of the
      complex hand syndactyly. The main target in our surgical strategy involved early
      bilateral separation of border digits, which started between 1 and 2 years of
      age. The unilateral middle syndactyly mass division with osteotomy of the thumb
      and other digits and bone grafting (as required) was carried out in later
      surgeries, which are usually completed by 4 years of age. The evaluation of the
      results was performed based on the functional results of the hand, morbidity,
      flap necrosis, skin graft lysis, postoperative range of motion in the small
      joints, gross grasp, pincer grasp, scar appearance, contractures of digits, and
      aesthetic outcome. CONCLUSION: As intended, this study proves the need for a
      complex surgical approach as early as possible with low revision rate, and
      acceptable functional and aesthetic outcome.

PMID- 23170943
TI  - Successful replantation of a completely amputated ear on a child.
AB  - Amputation of an ear is a rare injury. Subsequent replantation is a challenging
      and very difficult task for an experienced micro-surgeon. Every well described
      successful replantation of an ear is a valuable lesson for a micro-surgeon mainly
      because securing the venous drainage of the replanted ear is very difficult. In
      the worldwide medical literature, only a minimal amount of cases have described a
      successful replantation of an ear after total amputation on a child. The authors
      describe the whole treatment process for a seven-year old boy whose ear was
      bitten off by a dog. They also describe their procedures which led to a
      successful outcome.

PMID- 23170944
TI  - Middle phalangeal distal condylar fracture remodelling in children: a case
      report.
AB  - We report on a 9-year-old girl who sustained an injury to her left middle finger
      with a piece of metal 2 months before she presented to our clinic. In the acute
      trauma phase she applied ice to her hand and did not consult a medical
      practitioner about the pain and swelling on her finger. Two months after the
      injury she came to us with a palpable mass on the volar side of middle phalanx.
      On lateral radiographic view, an apex volar angulation measuring approximately 45
      degrees of vertically splitting midphalangeal fracture was noted. Bone
      remodelling was also seen dorsally extending from the midphalanx to the level of
      the DIP joint. During the operation the remodelled bone seemed to be in unity
      with the DIP joint. The apex volarly angulated distal fragment of the middle
      phalanx was osteotomized. In the postoperative 24 months a control radiologic
      view was obtained. Normal phalangeal alignment was noted.

PMID- 23170945
TI  - Tailoring the chain packing in ultrathin polyelectrolyte films formed by
      sequential adsorption: nanoscale probing by positron annihilation spectroscopy.
AB  - Depth profiling experiments by positron annihilation spectroscopy have been used
      to investigate the free volume element size and concentration in films assembled
      using the layer-by-layer (LbL) adsorption method. Films prepared from strong
      polyelectrolytes, weak polyelectrolytes, hydrogen-bonding polymers, and blended
      polyelectrolyte multilayers have different chain packing that is reflected in the
      free volume characteristics. The influence of various parameters on free volume,
      such as number of bilayers, salt concentration, solution pH, and molecular
      weight, has been systematically studied. The free volume cavity diameters vary
      from 4 to 6 A, and the free volume concentrations vary from (1.1-4.3) * 10(20)
      cm(-3), depending on the choice of assembly polymers and conditions. Films
      assembled from strong polyelectrolytes have fewer free volume cavities with a
      larger average size than films prepared from weak polyelectrolytes. Blending the
      weak polyanion poly(acrylic acid), PAA, with the strong polyanion poly(styrene
      sulfonate), PSS, to layer alternately with the polycation poly(allyamine
      hydrochloride), PAH, is shown to be a viable method to achieve intermediate free
      volume characteristics in these LbL films. An increase in salt concentration of
      the adsorption solutions for films prepared from strong polyelectrolytes makes
      these films tend toward weaker polyelectrolyte free volume characteristics.
      Hydrogen-bonded layered films show larger free volume element size and
      concentration than do their electrostatically bonded counterparts, while reducing
      the molecular weight of these hydrogen-bonded polymers results in slightly
      reduced free volume size and concentration. A study of the effect of solution pH
      on films prepared from weak polyelectrolytes shows that when both
      polyelectrolytes are substantially charged in solution (assembly pH = 7.5), the
      chains pack similarly to strong polyelectrolytes (i.e., lower free volume
      concentration), but with smaller average cavity sizes. These results give, for
      the first time, a clear indication of how the free volume profile develops in LbL
      thin films, offering numerous methods to tailor the Angstrom-scale free volume
      properties by judicious selection of the assembly polymers and conditions. These
      findings can be potentially exploited to tailor the properties of thin polymer
      films for applications spanning membranes, sensing, and drug delivery.

PMID- 23170946
TI  - New insight into the atomic structure of electrochemically delithiated O3-Li(1
      x)CoO2 (0 <= x <= 0.5) nanoparticles.
AB  - Direct observation of delithiated structures of LiCoO(2) at atomic scale has been
      achieved using spherical aberration-corrected scanning transmission electron
      microscopy (STEM) with high-angle annular-dark-field (HAADF) and annular-bright
      field (ABF) techniques. The ordered Li, Co, and O columns for LiCoO(2)
      nanoparticles are clearly identified in ABF micrographs. Upon the Li ions
      extraction from LiCoO(2), the Co-contained (003) planes distort from the bulk to
      the surface region and the c-axis is expanded significantly. Ordering of lithium
      ions and lithium vacancies has been observed directly and explained by first
      principles simulation. On the basis of HAADF micrographs, it is found that the
      phase irreversibly changes from O3-type in pristine LiCoO(2) to O1-type
      Li(x)CoO(2) (x ~ 0.50) after the first electrochemical Li extraction and back to
      O2-type Li(x)CoO(2) (x ~ 0.93) rather than to O3-stacking after the first
      electrochemical lithiation. This is the first report of finding O2-Li(x)CoO(2) in
      the phase diagram of O3-LiCoO(2), through which the two previously separated
      LiCoO(2) phases, i.e. O2 and O3 systems, are connected. These new investigations
      shed new insight into the lithium storage mechanism in this important cathode
      material for Li-ion batteries.

PMID- 23170947
TI  - Describing the appearance and flavor profiles of fresh fig (Ficus carica L.)
      cultivars.
AB  - Twelve fig cultivars, including cultivars destined for the fresh and dried
      markets, were harvested from 6 locations and evaluated by a trained panel using
      descriptive sensory analysis. Instrumental measurements were taken at harvest and
      also during sensory analysis. Each fresh fig cultivar had a characteristic
      appearance and flavor sensory profile regardless of the source. The primary
      flavor attributes used to describe the fig cultivars were "fruity,""melon,""stone
      fruit,""berry,""citrus,""honey,""green," and "cucumber." Maturity levels
      significantly affected the chemical composition and sensory profiles of the fig
      cultivars. Less mature figs had a higher compression force, a thicker outer skin,
      and higher ratings for "green" and "latex" flavors, firmness, graininess,
      bitterness, tingling, and seed adhesiveness. Meanwhile, more mature figs had
      higher soluble solids concentration, and were perceptibly higher in "fruit"
      flavors, juiciness, stickiness, sliminess, and sweetness. The specific sensory
      terminology used for fig appearance and flavor profiles will assist with
      communication between marketers and consumers, which can increase fresh fig
      consumption.

PMID- 23170948
TI  - Association between functional tooth units and chewing ability in older adults: a
      systematic review.
AB  - OBJECTIVES: To systematically review the current evidence on the relationship
      between dentition status and chewing ability in older adults, as the latter was
      subjectively perceived by questionnaires. BACKGROUND: Tooth loss is associated
      with functional impairment regarding chewing ability, depending on the number and
      the location of the remaining teeth. METHODS: A search of the English literature
      was undertaken using the appropriate electronic databases and keywords in order
      to answer the question of this review. Independent extraction of the related
      articles was carried out by two authors using predefined eligibility criteria.
      RESULTS: Full-text analysis was performed for 51 articles of possible relevance.
      Finally, data were extracted from 18 studies, published in 20 articles that met
      the inclusion criteria. CONCLUSIONS: Although there was a conflict between the
      studies relevant to the number of functional tooth units needed to maintain
      adequate oral function, it was revealed that chewing ability was closely related
      to the number and distribution of teeth remaining. Treatment plan should focus on
      the preservation of the strategic parts of the dental arch that are critical for
      adequate oral function. Long-term prospective studies, comprising well-defined
      criteria, clinical variables, methods and utilising comprehensive questionnaires,
      should be preferred to obtain a clearer picture on the association between
      masticatory ability and functional tooth units.

PMID- 23170949
TI  - Mushroom body-preferential expression of proteins/genes involved in endoplasmic
      reticulum Ca(2+)-transport in the worker honeybee (Apis mellifera L.) brain.
AB  - To identify the molecular characteristics specific to the mushroom body (MB, a
      higher processing centre) neurones in the honeybee brain, we previously used
      proteomics to identify proteins that are preferentially expressed in these MBs.
      Here we continued our proteomic analysis to show that reticulocalbin, which is
      involved in endoplasmic reticulum (ER) Ca(2+) transport, is also preferentially
      expressed in the MBs in the honeybee brain. Gene expression analysis revealed
      that reticulocalbin is preferentially expressed in the large-type Kenyon cells,
      which are MB-intrinsic neurones. In addition, the gene for the ryanodine
      receptor, which is also involved in ER Ca(2+) transport, was also preferentially
      expressed in the large-type Kenyon cells. In contrast, the expression of three
      other ER-related genes, protein disulphide isomerase, sec61 and erp60, was not
      enriched in the MBs. These findings further support the notion that the function
      of ER Ca(2+)-signalling, but not the mere intracellular density of ER, is
      specifically enhanced in the large-type Kenyon cells in the honeybee brain.

PMID- 23170950
TI  - Green tea consumption and risk of esophageal cancer: a meta-analysis of
      epidemiologic studies.
AB  - BACKGROUND: Green tea has shown the role of chemoprevention for cancer. Recently,
      several studies suggested that green tea intake may have effect on esophageal
      cancer risk, whereas the results were inconsistent. METHODS: We performed a meta
      analysis of all English and Chinese language studies of green tea consumption and
      esophageal cancer risk indexed in Medline, Embase, the Science Citation Index,
      the Chinese Biomedical Database and Wanfang Data from 1980 to June 2012. After
      reviewing each study, extracting data, and evaluating heterogeneity (Chi-square
      based Q test and Iota2) and publication bias (Begg and Egger test), a meta
      analysis was performed to evaluate the association between high/medium/low green
      tea consumption and non-drinking esophageal cancer risk. Pooled relative risk
      (RR) or odds ratio (OR) with 95% confidence intervals (CIs) were calculated using
      the fixed- or random-effect models. RESULTS: Ten eligible epidemiologic studies
      including 33731 participants and 3557 cases for esophageal cancer were included.
      Eight of which were case-control studies, and two were cohort studies. Overall,
      there were no association between high/medium/low green tea consumption and non
      drinking risk of esophageal cancer (High: highest vs non-drinker: RR/OR = 0.76,
      95% CI: 0.49 to 1.02. Medium: drinker vs non-drinker: RR/OR = 0.86, 95% CI: 0.70
      to 1.03. Low: lowest vs non-drinker: RR/OR = 0.83, 95% CI: 0.58 to 1.08). When
      stratified analyses according to study design (case-control and cohort studies),
      country (China and Japan), participates source (population-based and hospital
      based case-control), and gender (female and male), there were significant
      association between high/medium/low green tea consumption and non-drinking risk
      of esophageal cancer among female (High: RR/OR = 0.32, 95% CI: 0.10 to 0.54.
      Medium: RR/OR = 0.43, 95% CI: 0.21 to 0.66. Low: RR/OR = 0.45, 95% CI: 0.10 to
      0.79), but not the others. CONCLUSIONS: We did not found significant association
      between green tea consumption and non-drinking esophageal cancer risk, but an
      evidence of protective effect was observed among female.

PMID- 23170951
TI  - A cross-sectional survey of quality of life in colostomates: a report from Iran.
AB  - BACKGROUND: Considering the complications that colostomies may cause, patient
      self-assessments of their social, emotional, physical, sexual and functional
      conditions may help their surgeons to evaluate the impact of their interventions
      or use supplementary methods to maintain patient functional status or decrease
      its loss to the minimum level. The aim of this study was to evaluate the Quality
      of Life in Iranian patients with colostomies and to compare the age and gender
      differences among them. METHOD: This cross-sectional study was conducted from
      2009 to 2010 to evaluate the quality of life of 96 patients who had undergone
      surgery for rectal cancer and had permanent colostomies. The European
      Organization for Research and Treatment of Cancers Quality of Life Questionnaire
      (EORTC QLQ)-C30 and the EORTC QLQ-CR38 were used to assess patient Quality of
      Life. RESULTS: The mean scores for the functional subscales were as follows:
      Physical Function, 70.9 (+/-2.2); Role Function, 68.4 (+/-2.6); Emotional
      Function, 56.9 (+/-2.7); Cognitive Function, 68.7 (+/- 2.6); and Social Function,
      64.2 (+/-3.3). The EORTC questionnaires showed significant differences between
      males and females. Males had better body image scores. Sexual Function and Sexual
      Enjoyment were impaired in both males and females, but males had significantly
      higher scores and better roles in Physical and Sexual Functions. More sexual
      enjoyment problems in older ages were observed in both males and females.
      CONCLUSION: Having a colostomy was associated with a high level of emotional and
      sexual function impairment. The differing challenges between males and females
      should encourage us to design sex-specific interventions that improve the quality
      of life in this group of patients.

PMID- 23170952
TI  - World medical leaders declare that pain treatment is a human right ... and it
      couldn't come at a worse time.

PMID- 23170953
TI  - Copper-dependent cytotoxicity of 8-hydroxyquinoline derivatives correlates with
      their hydrophobicity and does not require caspase activation.
AB  - This study reports the structure-activity relationship of a series of 8
      hydroxoquinoline derivatives (8-HQs) and focuses on the cytotoxic activity of 5
      Cl-7-I-8-HQ (clioquinol, CQ) copper complex (Cu(CQ)). 8-HQs alone cause a dose
      dependent loss of viability of the human tumor HeLa and PC3 cells, but the
      coadministration of copper increases the ligands effects, with extensive cell
      death occurring in both cell lines. Cytotoxic doses of Cu(CQ) promote
      intracellular copper accumulation and massive endoplasmic reticulum vacuolization
      that precede a nonapoptotic (paraptotic) cell death. The cytotoxic effect of
      Cu(CQ) is reproduced in normal human endothelial cells (HUVEC) at concentrations
      double those effective in tumor cells, pointing to a potential therapeutic window
      for Cu(CQ). Finally, the results show that the paraptotic cell death induced by
      Cu(CQ) does not require nor involve caspases, giving an indication for the
      current clinical assessment of clioquinol as an antineoplastic agent.

PMID- 23170955
TI  - The cost-effectiveness of tracking newborns with bilateral hearing impairment in
      Bavaria: a decision-analytic model.
AB  - BACKGROUND: Although several countries, including Germany, have established
      newborn hearing screening programmes for early detection and treatment of
      newborns with hearing impairments, nationwide tracking systems for follow-up of
      newborns with positive test results until diagnosis of hearing impairment have
      often not been implemented. However, a recent study on universal newborn hearing
      screening in Bavaria showed that, in a high proportion of newborns, early
      diagnosis was only possible with the use of a tracking system. The aim of this
      study was, therefore, to assess the cost-effectiveness of tracking newborns with
      bilateral hearing impairment in Bavaria. METHODS: Data from a Bavarian pilot
      project on newborn hearing screening and Bavarian newborn hearing screening
      facilities were used to assess the cost-effectiveness of the inclusion of a
      tracking system within a newborn hearing screening programme. A model-based cost
      effectiveness analysis was conducted. The time horizon of the model was limited
      to the newborn hearing screening programme. Costs of the initial hearing
      screening test and subsequent tests were included, as well as costs of diagnosis
      and costs of tracking. The outcome measure of the economic analysis was the cost
      per case of bilateral hearing impairment detected. In order to reflect
      uncertainty, deterministic and probabilistic sensitivity analyses were performed.
      RESULTS: The incremental cost-effectiveness ratio of tracking vs. no tracking was
      ?1,697 per additional case of bilateral hearing impairment detected. CONCLUSIONS:
      Compared with no tracking, tracking resulted in more cases of bilateral hearing
      impairment detected as well as higher costs. If society is willing to pay at
      least ?1,697 per additional case of bilateral hearing impairment detected,
      tracking can be recommended.

PMID- 23170954
TI  - Getting in shape: controlling peptide bioactivity and bioavailability using
      conformational constraints.
AB  - Chemical biologists commonly seek out correlations between the physicochemical
      properties of molecules and their behavior in biological systems. However, a new
      paradigm is emerging for peptides in which conformation is recognized as the
      primary determinant of bioactivity and bioavailability. This review highlights an
      emerging body of work that directly addresses how a peptide's conformation
      controls its biological effects, cell penetration, and intestinal absorption.
      Based on this work, the dream of mimicking the potency and bioavailability of
      natural product peptides is getting closer to reality.

PMID- 23170956
TI  - The potential of bacteria isolated from ruminal contents of seaweed-eating North
      Ronaldsay sheep to hydrolyse seaweed components and produce methane by anaerobic
      digestion in vitro.
AB  - The production of methane biofuel from seaweeds is limited by the hydrolysis of
      polysaccharides. The rumen microbiota of seaweed-eating North Ronaldsay sheep was
      studied for polysaccharidic bacterial isolates degrading brown-seaweed
      polysaccharides. Only nine isolates out of 65 utilized >90% of the polysaccharide
      they were isolated on. The nine isolates (eight Prevotella spp. and one
      Clostridium butyricum) utilized whole Laminaria hyperborea extract and a range of
      seaweed polysaccharides, including alginate (seven out of nine isolates),
      laminarin and carboxymethylcellulose (eight out of nine isolates); while two out
      of nine isolates additionally hydrolysed fucoidan to some extent. Crude enzyme
      extracts from three of the isolates studied further had diverse glycosidases and
      polysaccharidase activities; particularly against laminarin and alginate (two
      isolates were shown to have alginate lyase activity) and notably fucoidan and
      carageenan (one isolate). In serial culture rumen microbiota hydrolysed a range
      of seaweed polysaccharides (fucoidan to a notably lesser degree) and homogenates
      of L. hyperborea, mixed Fucus spp. and Ascophyllum nodosum to produce methane and
      acetate. The rumen microbiota and isolates represent potential adjunct organisms
      or enzymes which may improve hydrolysis of seaweed components and thus improve
      the efficiency of seaweed anaerobic digestion for methane biofuel production.

PMID- 23170957
TI  - Spo0A links de novo fatty acid synthesis to sporulation and biofilm development
      in Bacillus subtilis.
AB  - During sporulation in Bacillus subtilis, the committed-cell undergoes substantial
      membrane rearrangements to generate two cells of different sizes and fates: the
      mother cell and the forespore. Here, we demonstrate that the master transcription
      factor Spo0A reactivates lipid synthesis during development. Maximal Spo0A
      dependent lipid synthesis occurs during the key stages of asymmetric division and
      forespore engulfment. Spo0A reactivates the accDA operon that encodes the
      carboxylase component of the acetyl-CoA carboxylase enzyme, which catalyses the
      first and rate-limiting step in de novo lipid biosynthesis, malonyl-CoA
      formation. The disruption of the Spo0A-binding box in the promoter region of
      accDA impairs its transcriptional reactivation and blocks lipid synthesis. The
      Spo0A-insensitive accDA(0A)  cells were proficient in planktonic growth but
      defective in sporulation (sigma(E)  activation) and biofilm development (cell
      cluster formation and water repellency). Exogenous fatty acid supplementation to
      accDA(0A)  cells overcomes their inability to synthesize lipids during
      development and restores sporulation and biofilm proficiencies. The transient
      exclusion of the lipid synthesis regulon from the forespore and the known
      compartmentalization of Spo0A and ACP in the mother cell suggest that de novo
      lipid synthesis is confined to the mother cell. The significance of the Spo0A
      controlled de novo lipid synthesis during B. subtilis development is discussed.

PMID- 23170959
TI  - Double layered hydroxides as potential anti-cancer drug delivery agents.
AB  - The emergence of nanotechnology has changed the scenario of the medical world by
      revolutionizing the diagnosis, monitoring and treatment of cancer. This
      nanotechnology has been proved miraculous in detecting cancer cells, delivering
      chemotherapeutic agents and monitoring treatment from non-specific to highly
      targeted killing of tumor cells. In the past few decades, a number of inorganic
      materials have been investigated such as calcium phosphate, gold, carbon
      materials, silicon oxide, iron oxide, and layered double hydroxide (LDH) for
      examining their efficacy in targeting drug delivery. The reason behind the
      selection of these inorganic materials was their versatile and unique features
      efficient in drug delivery, such as wide availability, rich surface
      functionality, good biocompatibility, potential for target delivery, and
      controlled release of the drug from these inorganic nanomaterials. Although, the
      drug-LDH hybrids are found to be quite instrumental because of their application
      as advanced anti-cancer drug delivery systems, there has not been much research
      on them. This mini review is set to highlight the advancement made in the use of
      layered double hydroxides (LDHs) as anti-cancer drug delivery agents. Along with
      the advantages of LDHs as anti-cancer drug delivery agents, the process of
      interaction of some of the common anti-cancer drugs with LDH has also been
      discussed.

PMID- 23170958
TI  - A rare case of primary clear cell sarcoma of the pubic bone resembling small
      round cell tumor: an unusual morphological variant.
AB  - BACKGROUND: Clear cell sarcoma (CCS) and malignant melanoma share overlapping
      immunohistochemistry with regard to the melanocytic markers HMB45, S100, and
      Melan-A. However, the translocation t(12; 22)(q13; q12) is specific to CCS.
      Therefore, although these neoplasms are closely related, they are now considered
      to be distinct entities. However, the translocation is apparently detectable only
      in 50%-70% of CCS cases. Therefore, the absence of a detectable EWS/AFT1
      rearrangement may occasionally lead to erroneous exclusion of a translocation
      negative CCS. Therefore, histological assessment is essential for the correct
      diagnosis of CCS. Primary CCS of the bone is exceedingly rare. Only a few cases
      of primary CCS arising in the ulna, metatarsals, ribs, radius, sacrum, and
      humerus have been reported, and primary CCS arising in the pubic bone has not
      been reported till date. CASE PRESENTATION: We present the case of an 81-year-old
      man with primary CCS of the pubic bone. Histological examination of the pubic
      bone revealed monomorphic small-sized cells arranged predominantly as a diffuse
      sheet with round, hyperchromatic nuclei and inconspicuous nucleoli. The cells had
      scant cytoplasm, and the biopsy findings indicated small round cell tumor (SRCT).
      Immunohistochemical staining revealed the tumor cells to be positive for HMB45,
      S100, and Melan-A but negative for cytokeratin (AE1/AE3) and epithelial membrane
      antigen. To the best of our knowledge, this is the first case report of primary
      CCS of the pubic bone resembling SRCT. This ambiguous appearance underscores the
      difficulties encountered during the histological diagnosis of this rare variant
      of CCS. CONCLUSION: Awareness of primary CCS of the bone is clinically important
      for accurate diagnosis and management when the tumor is located in unusual
      locations such as the pubic bone and when the translocation t(12; 22)(q13; q12)
      is absent.

PMID- 23170960
TI  - Structure based lead optimization approach in discovery of selective DPP4
      inhibitors.
AB  - Diabetes mellitus is a chronic progressive metabolic disorder that has profound
      consequences for individuals, families, and society. To date, main available oral
      antidiabetic medications target either insulin resistance (metformin,
      glitazones), or insulin deficiency (sulfonylureas, glinides), but leading to
      shortfalls in medication. Advancement in modern oral hypoglycemic agents may be
      encouraged with or in place of traditional therapies. The lower risk for
      hypoglycemic events as compared with other insulinotropic or insulin-sensitizing
      agents make DPP-4 inhibitors very promising candidates for a more physiological
      treatment of type-2 diabetes. Only some DPP-4 inhibitors are currently used for
      the treatment of type 2 diabetes (T2DM) and various inhibitors currently
      undergoing animal and human testing. A number of catalytically active DPPs
      distinct from DPP-4 (DPP II, FAP, DPP-8, and DPP-9) have been described that is
      associated with side-effect and toxicity. To discover potent and selective and
      safer drugs in a shorter time frame and with reduced cost it requires using an
      innovative approach for designing novel inhibitors. This review article focuses
      on the status of advanced lead candidates of DPP group and their binding affinity
      with the active site residue of target structure which help in discovery of
      potent and selective DPP-4 inhibitors by lead optimization approach.

PMID- 23170961
TI  - Dense mapping of IL2RA shows no association with Graves' disease in Chinese Han
      population.
AB  - OBJECTIVE: Associations between IL2RA and various autoimmune diseases have been
      reported in Caucasians. We investigated whether genetic polymorphisms at the
      IL2RA locus were associated with Graves' disease (GD) in the Chinese Han
      population. DESIGN: We performed a genome-wide association study (GWAS) in 1 536
      GD patients and 1 516 controls. The 1000 Genomes Project data were adopted as
      references for imputation analysis. After forward and conditional logistic
      regressions, we found that rs11256313 was the major risk variant in the
      CD25/IL2RA region. Thus, we further genotyped rs11256313 in a replication cohort
      with 3 694 GD patients and 3 510 controls using ABI 7900HT TaqMan Real-Time PCR
      System. RESULTS: Nine single nucleotide polymorphisms (SNPs) in the IL2RA block
      were nominally associated with GD in our GWAS (0.01 < P < 0.05). After imputation
      analysis, 13 imputed SNPs in the IL2RA block were weakly associated with GD (P <=
      0.05). Logistic regression analysis suggested that the imputed rs11256313 could
      represent the IL2RA block (P = 0.003). However, we failed to replicate the
      association of rs11256313 in a larger cohort (P = 0.145). A subphenotype analysis
      of rs11256313 on thyroid hormone receptor antibody (TRAb) and gender showed that
      there was no association in any of the subphenotype groups (P > 0.05).
      CONCLUSIONS: The results suggested that common genetic polymorphisms at IL2RA do
      not exert a significant genetic effect on the development of GD in the Chinese
      Han population. Previously reported associations between CD25/IL2RA and
      autoimmune diseases including GD in Caucasians again imply that heterogeneity
      exists in different ethnic populations.

PMID- 23170962
TI  - The non-mammalian host Galleria mellonella can be used to study the virulence of
      the fungal pathogen Candida tropicalis and the efficacy of antifungal drugs
      during infection by this pathogenic yeast.
AB  - Although Candida tropicalis is a frequent cause of invasive fungal diseases, its
      interaction with the host remains poorly studied. Galleria mellonella is a
      Lepidoptera model which offers a useful tool to study virulence of different
      microorganisms and drug efficacy. In this work we investigated the virulence of
      C. tropicalis in G. mellonella at different temperatures and the efficacy of
      antifungal drugs in this infection model. When larvae were infected with yeast
      inocula suspensions of different concentrations (4 * 10(6), 2 * 10(6), 10(6) and
      5 * 10(5) cells/larva), we observed a dose-dependent effect on the killing of the
      insect (50% survival ranging from 1.4 +/- 0.8 to 8.8 +/- 1.2 days with the higher
      and lower inocula, respectively). Candida tropicalis killed G. mellonella larvae
      at both 30 degrees C and 37 degrees C, although at 37 degrees C the virulence was
      more evident. Haemocytes phagocytosed C. tropicalis cells after 2 hours of
      infection, although the phagocytosis rate was lower when compared with other
      fungal pathogens, such as Cryptococcus neoformans. Moreover, the haemocyte
      density in the haemolymph decreased during infection and the yeast formed
      pseudohyphae in G. mellonella. The efficacy of amphotericin B, caspofungin,
      fluconazole and voriconazole was tested at different concentrations, and a
      protective effect was observed with all the drugs at concentrations equivalent to
      therapeutic dose. Fungal burden increased in infected larvae during time of
      infection and amphotericin B and fluconazole reduced the number of colony-forming
      units in the worms. Moreover, antifungal treatment was associated with the
      presence of cell aggregates around infected areas. We conclude that G. mellonella
      offers a simple and feasible model to study C. tropicalis virulence and drug
      efficacy.

PMID- 23170963
TI  - An atypical, pigment-producing Metschnikowia strain from a leukaemia patient.
AB  - A yeast strain was isolated from the sputum sample of a leukaemia patient in the
      Spirito Santo Hospital of Pescara, Italy. The fungus produced a pigment that
      formed a reddish halo around colonies, and was identified and deposited as a
      Metschnikowia spp. (accession number IHEM 25107-GenBank accession number
      JQ921016) in the BCCM/IHEM collection of biomedical fungi and yeasts (Bruxelles,
      Belgium). Although the physiology of the strain was close to that of
      Metschnikowia sinensis, the D1/D2 sequence did not correspond to any previously
      described Metschnikowia species. Phylogeny of the genus Metschnikowia is complex
      and requires far more analysis. We present the first non-M. pulcherrima
      Metschnikowia spp. isolate recovered from a human, and emphasize the role of man
      as a transient carrier of environmental yeasts, the pathogenicity of which still
      needs to be defined.

PMID- 23170964
TI  - Getting better at chronic care in remote communities: study protocol for a
      pragmatic cluster randomised controlled of community based management.
AB  - BACKGROUND: Prevalence and incidence of diabetes and other common comorbid
      conditions (hypertension, coronary heart disease, renal disease and chronic lung
      disease) are extremely high among Indigenous Australians. Recent measures to
      improve quality of preventive care in Indigenous community settings, while
      apparently successful at increasing screening and routine check-up rates, have
      shown only modest or little improvements in appropriate care such as the
      introduction of insulin and other scaled-up drug regimens in line with evidence
      based guidelines, together with support for risk factor reduction. A new strategy
      is required to ensure high quality integrated family-centred care is available
      locally, with continuity and cultural safety, by community-based care
      coordinators with appropriate system supports. METHODS/DESIGN: The trial design
      is open parallel cluster randomised controlled trial. The objective of this
      pragmatic trial is to test the effectiveness of a model of health service
      delivery that facilitates integrated community-based, intensive chronic condition
      management, compared with usual care, in rural and remote Indigenous primary
      health care services in north Queensland. Participants are Indigenous adults
      (aged 18-65 years) with poorly controlled diabetes (HbA1c>=8.5) and at least one
      other chronic condition. The intervention is to employ an Indigenous Health
      Worker to case manage the care of a maximum caseload of 30 participants. The
      Indigenous Health Workers receive intensive clinical training initially, and
      throughout the study, to ensure they are competent to coordinate care for people
      with chronic conditions. The Indigenous Health Workers, supported by the local
      primary health care (PHC) team and an Indigenous Clinical Support Team, will
      manage care, including coordinating access to multidisciplinary team care based
      on best practice standards. Allocation by cluster to the intervention and control
      groups is by simple randomisation after participant enrolment. Participants in
      the control group will receive usual care, and will be wait-listed to receive a
      revised model of the intervention informed by the data analysis. The primary
      outcome is reduction in HbA1c measured at 18 months. Implementation fidelity will
      be monitored and a qualitative investigation (methods to be determined) will aim
      to identify elements of the model which may influence health outcomes for
      Indigenous people with chronic conditions. DISCUSSION: This pragmatic trial will
      test a culturally-sound family-centred model of care with supported case
      management by IHWs to improve outcomes for people with complex chronic care
      needs. This trial is now in the intervention phase. TRIAL REGISTRATION:
      Australian New Zealand Clinical Trials Registry ACTR12610000812099.

PMID- 23170965
TI  - An assessment on epitope prediction methods for protozoa genomes.
AB  - BACKGROUND: Epitope prediction using computational methods represents one of the
      most promising approaches to vaccine development. Reduction of time, cost, and
      the availability of completely sequenced genomes are key points and highly
      motivating regarding the use of reverse vaccinology. Parasites of genus
      Leishmania are widely spread and they are the etiologic agents of leishmaniasis.
      Currently, there is no efficient vaccine against this pathogen and the drug
      treatment is highly toxic. The lack of sufficiently large datasets of
      experimentally validated parasites epitopes represents a serious limitation,
      especially for trypanomatids genomes. In this work we highlight the predictive
      performances of several algorithms that were evaluated through the development of
      a MySQL database built with the purpose of: a) evaluating individual algorithms
      prediction performances and their combination for CD8+ T cell epitopes, B-cell
      epitopes and subcellular localization by means of AUC (Area Under Curve)
      performance and a threshold dependent method that employs a confusion matrix; b)
      integrating data from experimentally validated and in silico predicted epitopes;
      and c) integrating the subcellular localization predictions and experimental
      data. NetCTL, NetMHC, BepiPred, BCPred12, and AAP12 algorithms were used for in
      silico epitope prediction and WoLF PSORT, Sigcleave and TargetP for in silico
      subcellular localization prediction against trypanosomatid genomes. RESULTS: A
      database-driven epitope prediction method was developed with built-in functions
      that were capable of: a) removing experimental data redundancy; b) parsing
      algorithms predictions and storage experimental validated and predict data; and
      c) evaluating algorithm performances. Results show that a better performance is
      achieved when the combined prediction is considered. This is particularly true
      for B cell epitope predictors, where the combined prediction of AAP12 and
      BCPred12 reached an AUC value of 0.77. For T CD8+ epitope predictors, the
      combined prediction of NetCTL and NetMHC reached an AUC value of 0.64. Finally,
      regarding the subcellular localization prediction, the best performance is
      achieved when the combined prediction of Sigcleave, TargetP and WoLF PSORT is
      used. CONCLUSIONS: Our study indicates that the combination of B cells epitope
      predictors is the best tool for predicting epitopes on protozoan parasites
      proteins. Regarding subcellular localization, the best result was obtained when
      the three algorithms predictions were combined. The developed pipeline is
      available upon request to authors.

PMID- 23170966
TI  - Prevalence, risk factors, and consequences of overweight in children and
      adolescents who underwent renal transplantation--short- and medium-term analysis.
AB  - To determine the prevalence and risk factors for (i) overweight/obesity and (ii)
      weight gain six months after transplantation and to study the effect of weight
      excess on graft function and survival. We performed a retrospective study of
      kidney transplanted children. ENDPOINTS: (i) prevalence of overweight/obesity at
      sixth month, (ii) gaining 1.0 BMI SDS from one to six months. To study the
      effects of weight excess, graft function and survival at 36 months were the
      endpoints. The study included 197 individuals. At sixth month, 57/197 (29%)
      presented overweight/obesity, and the factors associated to this outcome were:
      (i) age at transplantation (OR = 3.04) and (ii) overweight/obesity in the first
      month (OR = 22.16). Groups presented no difference on graft function and survival
      at 36 months. From one to six months, 90/197 (46%) patients gained >1.0 BMI SDS.
      This outcome was associated with (i) female sex (OR = 2.50), (ii) steroids'
      pulses (OR = 2.98), (iii) steroids exposure (OR = 1.04), and (iv) living donor
      (OR = 2.69). The group that gained BMI presented a lower 36 months graft survival
      (86% vs. 98%, p < 0.001). Weight excess and gain after transplantation are
      frequent, particularly in younger female recipients and in those receiving high
      steroids exposure. The lower graft survival in patients with rapid weight gain
      deserves investigation.

PMID- 23170968
TI  - Inotropes for the management of acute heart failure patients with renal
      dysfunction. Still an option?
AB  - INTRODUCTION: Renal dysfunction is highly prevalent in patients with acute heart
      failure (AHF). These patients are more vulnerable in worsening of kidney function
      and have also higher mortality rates. AREAS COVERED: Recent developments in the
      understanding of bidirectional interaction between heart and kidney are reviewed
      in the context of the potential impact of inotropes on renal function. Key
      clinical trials reporting the use of inotropes in AHF patients with renal
      dysfunction are discussed in this review. EXPERT OPINION: Inotropes may be
      indicated on a short-term basis and under close monitoring in AHF with renal
      dysfunction mostly in cases of low output heart failure that can provoke renal
      hypoperfusion. Dopamine administration with low dose of i.v. furosemide has been
      recently compared with high dose of i.v. furosemide alone, demonstrating lower
      rates of worsening renal function and electrolyte disturbances. Moreover, small
      clinical trials have shown that the novel inodilator levosimendan seems to be
      superior to dobutamine or placebo in improving renal function in patients with
      acutely decompensated heart failure. The impact of novel inotropes on kidney
      function is still unclear. Randomized clinical trials are required in order to
      identify the role of inotropes in the management and/or prevention of acute
      cardiorenal syndrome.

PMID- 23170969
TI  - High-temperature laser-scanning confocal microscopy as a tool to study the
      interface instability during unsteady-state solidification of low-carbon steel.
AB  - Solidification microstructure is a defining link between production techniques
      and the mechanical properties of metals and in particular steel. Due to the
      difficulty of conducting solidification studies at high temperature, knowledge of
      the development of solidification microstructure in steel is scarce. In this
      study, a laser-scanning confocal microscopy (LSCM) has been used to observe in
      situ and in real-time the planar to cellular to dendritic transition of the
      progressing solid/liquid interface in low carbon steel. Because the in situ
      observations in the laser-scanning confocal microscopy are restricted to the
      surface, the effect of sample thickness on surface observations was determined.
      Moreover, the effect of cooling rate and alloy composition on the planar to
      cellular interface transition was investigated. In the low-alloyed, low-carbon
      steel studied, the cooling rate does not seem to have an effect on the spacing of
      the cellular microstructure. However, in the presence of copper and manganese,
      the cell spacing decreased at higher cooling rates. Higher concentrations of
      copper in steel resulted on an increased cell spacing at the same cooling rates.

PMID- 23170970
TI  - Discovery of novel and ligand-efficient inhibitors of Plasmodium falciparum and
      Plasmodium vivax N-myristoyltransferase.
AB  - N-Myristoyltransferase (NMT) is an attractive antiprotozoan drug target. A lead
      hopping approach was utilized in the design and synthesis of novel
      benzo[b]thiophene-containing inhibitors of Plasmodium falciparum (Pf) and
      Plasmodium vivax (Pv) NMT. These inhibitors are selective against Homo sapiens
      NMT1 (HsNMT), have excellent ligand efficiency (LE), and display antiparasitic
      activity in vitro. The binding mode of this series was determined by
      crystallography and shows a novel binding mode for the benzothiophene ring.

PMID- 23170971
TI  - IgG and IgG4 antibodies in subjects with irritable bowel syndrome: a case control
      study in the general population.
AB  - BACKGROUND: Patients with Irritable Bowel Syndrome (IBS) often relate their
      symptoms to the intake of food and modify their diet. IgE-mediated food allergy
      is uncommon in IBS, but the role of IgG-mediated food hypersensitivity remains
      inconclusive. The primary aim of this study was to compare food- and yeast
      specific IgG and IgG4 antibodies in subjects with and without IBS. METHODS: This
      was a case control study in the general population for which subjects completed
      questionnaires about abdominal complaints and their intake of common food items.
      Blood samples were collected, and food- and yeast-specific IgG and IgG4
      antibodies were measured. Antibodies were measured in mg/L. RESULTS: We included
      269 subjects with IBS and 277 control subjects. After correction for subject
      characteristics and diet, there were no significant differences with regard to
      food- and yeast-specific IgG and IgG4 antibodies between subjects with IBS and
      controls. Lower values of IgG antibodies against egg (OR 0.99 (0.98 to 1.00), p =
      0.002) and beef (OR 0.75 (0.60 to 0.94), p = 0.012) and higher values of IgG
      antibodies against chicken (OR 1.14 (1.03 to 1.27), p = 0.009) were associated
      with more severe symptoms. CONCLUSIONS: Our findings suggest that IgG-and IgG4
      mediated food and yeast hypersensitivity in IBS is unlikely. IgG antibodies
      against food and yeast may reflect the diet.

PMID- 23170973
TI  - Multidrug resistance protein gene expression in Trichoplusia ni caterpillars.
AB  - Many insect species exhibit pesticide-resistant phenotypes. One of the mechanisms
      capable of contributing to resistance is the overexpression of multidrug
      resistance (MDR) transporter proteins. Here we describe the cloning of three
      genes encoding MDR proteins from Trichoplusia ni: trnMDR1, trnMDR2 and trnMDR3.
      Real-time quantitative PCR (qPCR) detected trnMDR mRNA in the whole nervous
      system, midgut and Malpighian tubules of final instar T. ni caterpillars. To test
      whether these genes are upregulated in response to chemical challenge in this
      insect, qPCR was used to compare trnMDR mRNA levels in unchallenged insects with
      those of insects fed the synthetic pyrethroid, deltamethrin. Only limited
      increases were detected in a single gene, trnMDR2, which is the most weakly
      expressed of the three MDR genes, suggesting that increased multidrug resistance
      of this type is not a significant part of the response to deltamethrin exposure.

PMID- 23170972
TI  - Overexpression of steroidogenic acute regulatory protein in rat aortic
      endothelial cells attenuates palmitic acid-induced inflammation and reduction in
      nitric oxide bioavailability.
AB  - BACKGROUND: Endothelial dysfunction is a well documented evidence for the onset
      of atherosclerosis and other cardiovascular diseases. Lipids disorder is among
      the main risk factors for endothelial dysfunction in these diseases.
      Steroidogenic acute regulatory protein (StAR), one of the cholesterol
      transporters, plays an important role in the maintenance of intracellular lipid
      homeostasis. However, the effect of StAR on endothelial dysfunction is not well
      understood. Palmitic acid (PA) has been shown to decrease eNOS activity and
      induce inflammation, both are the causes of endothelial dysfunction, in an
      endothelial cell culture model. METHODS: StAR gene was introduced into primary
      rat aortic endothelial cells by adenovirus infection. Real-time PCR and Western
      blotting were performed to determine the relative genes and proteins expression
      level to elucidate the underlying mechanism. The free fatty acid and cholesterol
      quantification kits were used to detect total cellular free fatty acid and
      cholesterol. The levels of inflammatory factors and nitric oxide were determined
      by ELISA and classic Griess reagent methods respectively. RESULTS: We
      successfully overexpressed StAR in primary rat aortic endothelial cells.
      Following StAR overexpression, mRNA levels of IL-1beta, TNFalpha, IL6 and VCAM-1
      and protein levels of IL-1beta, , TNFalpha and IL-6 in culture supernatant were
      significantly decreased, which duing to blocke NFkappaB nuclear translocation and
      activation. Moreover, StAR overexpression attenuated the PA-induced reduction of
      nitric oxide bioavailability by protecting the bioactivity of pAkt/peNOS/NO
      pathway. Furthermore, the key genes involved in lipid metabolism were greatly
      reduced following StAR overexpression. In order to investigate the underlying
      mechanism, cerulenin and lovastatin, the inhibitor of fatty acid and cholesterol
      synthase, were added prior to PA treatment. The results showed that both
      cerulenin and lovastatin had a similar effect as StAR overexpression. On the
      other hand, the role of StAR was inhibited when siRNA was introduced to reduce
      StAR expression. CONCLUSIONS: Our results showed that StAR attenuated lipid
      synthesis and uptake as well as PA-induced inflammation and reduction in NO
      bioavailability in aortic endothelial cells. StAR can ameliorate endothelial
      dysfunction induced by PA via reducing the intracellular lipid levels.

PMID- 23170976
TI  - Childhood recurrent urinary tract infection in southern Thailand.
AB  - INTRODUCTION: Recurrent urinary tract infection (UTI) is one of the major health
      problems in children because of its high rate of occurrence. OBJECTIVE: Our aim
      of the study was to evaluate the prevalence and determine risk factors of
      recurrent UTI in Thai children. PATIENTS AND METHODS: The medical records of
      children aged less than 15 years diagnosed with UTI at the Department of
      Pediatrics, Songklanagarind Hospital were reviewed. RESULTS: A total of 307
      children (144 boys, 163 girls) were followed up for at least 1 year. Fifty-six
      children, 31 (19.0%) boys and 25 (17.4%) girls, developed at least one recurrence
      totaling 153 recurrent UTI episodes. The recurrence rate was not statistically
      different between the sexes (p = 0.8). On multivariate analysis, genitourinary
      system (GU) anomalies, particularly vesicoureteral reflux (VUR), were the most
      significant risk factors. Children aged greater than 5 years had a slightly
      higher risk of recurrence, irrespective of gender. Comparison of organisms
      associated with recurrent UTI with those associated with first UTI showed that
      the prevalence of Escherichia coli decreased from 76.9% to 56.2% but was still
      the major causative agent. In contrast, the prevalence of Klebsiella pneumoniae
      and unusual or mixed organisms significantly increased from 7.8% to 15.0% and
      6.2% to 16.3%, respectively. CONCLUSION: One-fifth of children who had UTI
      developed recurrence and the rates were similar for males and females.
      Independent risk factors for recurrent UTI were found to be at age of >5 years
      and underlying disease of either GU anomaly or VUR.

PMID- 23170974
TI  - Integrated miRNA, mRNA and protein expression analysis reveals the role of post
      transcriptional regulation in controlling CHO cell growth rate.
AB  - BACKGROUND: To study the role of microRNA (miRNA) in the regulation of Chinese
      hamster ovary (CHO) cell growth, qPCR, microarray and quantitative LC-MS/MS
      analysis were utilised for simultaneous expression profiling of miRNA, mRNA and
      protein. The sample set under investigation consisted of clones with variable
      cellular growth rates derived from the same population. In addition to providing
      a systems level perspective on cell growth, the integration of multiple profiling
      datasets can facilitate the identification of non-seed miRNA targets, complement
      computational prediction tools and reduce false positive and false negative
      rates. RESULTS: 51 miRNAs were associated with increased growth rate (35 miRNAs
      upregulated and 16 miRNAs downregulated). Gene ontology (GO) analysis of genes
      (n=432) and proteins (n=285) found to be differentially expressed (DE) identified
      biological processes driving proliferation including mRNA processing and
      translation. To investigate the influence of miRNA on these processes we combined
      the proteomic and transcriptomic data into two groups. The first set contained
      candidates where evidence of translational repression was observed (n=158). The
      second group was a mixture of proteins and mRNAs where evidence of translational
      repression was less clear (n=515). The TargetScan algorithm was utilised to
      predict potential targets within these two groups for anti-correlated DE miRNAs.
      CONCLUSIONS: The evidence presented in this study indicates that biological
      processes such as mRNA processing and protein synthesis are correlated with
      growth rate in CHO cells. Through the integration of expression data from
      multiple levels of the biological system a number of proteins central to these
      processes including several hnRNPs and components of the ribosome were found to
      be post-transcriptionally regulated. We utilised the expression data in
      conjunction with in-silico tools to identify potential miRNA-mediated regulation
      of mRNA/proteins involved in CHO cell growth rate. These data have allowed us to
      prioritise candidates for cell engineering and/or biomarkers relevant to
      industrial cell culture. We also expect the knowledge gained from this study to
      be applicable to other fields investigating the role of miRNAs in mammalian cell
      growth.

PMID- 23170977
TI  - Probing the origins of glutathione biosynthesis through biochemical analysis of
      glutamate-cysteine ligase and glutathione synthetase from a model photosynthetic
      prokaryote.
AB  - Glutathione biosynthesis catalysed by GCL (glutamate-cysteine ligase) and GS
      (glutathione synthetase) is essential for maintaining redox homoeostasis and
      protection against oxidative damage in diverse eukaroytes and bacteria. This
      biosynthetic pathway probably evolved in cyanobacteria with the advent of
      oxygenic photosynthesis, but the biochemical characteristics of progenitor GCLs
      and GSs in these organisms are largely unexplored. In the present study we
      examined SynGCL and SynGS from Synechocystis sp. PCC 6803 using steady-state
      kinetics. Although SynGCL shares ~15% sequence identity with the enzyme from
      plants and alpha-proteobacteria, sequence comparison suggests that these enzymes
      share similar active site residues. Biochemically, SynGCL lacks the redox
      regulation associated with the plant enzymes and functions as a monomeric
      protein, indicating that evolution of redox regulation occurred later in the
      green lineage. Site-directed mutagenesis of SynGCL establishes this enzyme as
      part of the plant-like GCL family and identifies a catalytically essential
      arginine residue, which is structurally conserved across all forms of GCLs,
      including those from non-plant eukaryotes and gamma-proteobacteria. A reaction
      mechanism for the synthesis of gamma-glutamylcysteine by GCLs is proposed.
      Biochemical and kinetic analysis of SynGS reveals that this enzyme shares
      properties with other prokaryotic GSs. Initial velocity and product inhibition
      studies used to examine the kinetic mechanism of SynGS suggest that it and other
      prokaryotic GSs uses a random ter-reactant mechanism for the synthesis of
      glutathione. The present study provides new insight on the molecular mechanisms
      and evolution of glutathione biosynthesis; a key process required for enhancing
      bioenergy production in photosynthetic organisms.

PMID- 23170978
TI  - Transcriptional response of lignin-degrading enzymes to 17alpha-ethinyloestradiol
      in two white rots.
AB  - Fungal, ligninolytic enzymes have attracted a great attention for their
      bioremediation capabilities. A deficient knowledge of regulation of enzyme
      production, however, hinders the use of ligninolytic fungi in bioremediation
      applications. In this work, a transcriptional analyses of laccase and manganese
      peroxidase (MnP) production by two white rots was combined with determination of
      pI of the enzymes and the evaluation of 17alpha-ethinyloestradiol (EE2)
      degradation to study regulation mechanisms used by fungi during EE2 degradation.
      In the cultures of Trametes versicolor the addition of EE2 caused an increase in
      laccase activity with a maximum of 34.2 +/- 6.7 U g-1 of dry mycelia that was
      observed after 2 days of cultivation. It corresponded to a 4.9 times higher
      transcription levels of a laccase-encoding gene (lacB) that were detected in the
      cultures at the same time. Simultaneously, pI values of the fungal laccases were
      altered in response to the EE2 treatment. Like T. versicolor, Irpex lacteus was
      also able to remove 10 mg l-1 EE2 within 3 days of cultivation. While an increase
      to I. lacteus MnP activity and MnP gene transcription levels was observed at the
      later phase of the cultivation. It suggests another metabolic role of MnP but EE2
      degradation.

PMID- 23170979
TI  - Novel cancerization marker, TP53, and its role in distinguishing normal tissue
      adjacent to cancerous tissue from normal tissue adjacent to benign tissue.
AB  - BACKGROUND: The histopathological and molecular heterogeneity of normal tissue
      adjacent to cancerous tissue (NTAC) and normal tissue adjacent to benign tissue
      (NTAB), and the availability of limited specimens make deciphering the mechanisms
      of carcinogenesis challenging. Our goal was to identify histogenetic biomarkers
      that could be reliably used to define a transforming fingerprint using RNA in
      situ hybridization. METHODS: We evaluated 15 tumor-related RNA in situ
      hybridization biomarkers using tumor microarray and samples of seven tumor
      adjacent normal tissues from 314 patients. Biomarkers were determined using
      comprehensive statistical methods (significance of support vector machine-based
      artificial intelligence and area under curve scoring of classification
      distribution). RESULTS: TP53 was found to be a most reliable index (P <10(-7);
      area under curve >87%) for distinguishing NTAC from NTAB, according to the
      results of a significance panel (BCL10, BECN1, BRCA2, FITH, PTCH11 and TP53).
      CONCLUSIONS: The genetic alterations in TP53 between NTAC and NTAB may provide
      new insight into the field of cancerization and tumor transformation.

PMID- 23170980
TI  - The effect of molybdenum on the in vitro development of mouse preimplantation
      embryos.
AB  - The object of this study was to investigate the effect of molybdenum on the
      development of mouse preimplantation embryos cultured in vitro. Zygotes were
      flushed from one outbred mouse strain (Kunming), and then were cultured in
      potassium simplex optimized medium (KSOM) containing 0, 5, 10, 20, 40, 80, 120,
      and 160 ug/ml of molybdenum for 5 days until the mid-blastocyst stage. The
      addition of <= 20 ug/ml molybdenum did not affect the blastocyst and birth rates.
      Molybdenum at doses of 40 ug/ml and higher significantly decreased the cleavage,
      blastocyst and birth rates, the average cell number, and significantly increased
      the proportion of degenerative blastocysts. At 120 ug/ml molybdenum inhibited the
      blastocysts development to birth. At 160 ug/ml molybdenum caused overall
      developmental arrest (up to 16-cells) of embryos and their massive degeneration.
      In conclusion, molybdenum negatively affected the development of embryos in a
      dose-dependent manner. With lower doses (<= 20 ug/ml), mouse embryos were not
      apparently damaged. With very high doses (>= 40 ug/ml), embryo quality
      significantly decreased. This assessment of the effect of molybdenum on the
      preimplantation embryo is an initial survey of toxicological risk.

PMID- 23170983
TI  - Highly selective CO2 uptake in uninodal 6-connected "mmo" nets based upon MO4(2-)
      (M = Cr, Mo) pillars.
AB  - A novel 4(8).6(7) topology metal-organic material (MOM) platform of formula
      [M(bpe)(2)(M'O(4))] (M = Co or Ni; bpe = 1,2-bis(4-pyridyl)ethene; M' = Mo or Cr)
      has been synthesized and evaluated in the context of gas sorption. These MOMs
      have been assigned RCSR code mmo and are uninodal 6-connected nets.
      [Ni(bpe)(2)(MoO(4))], MOOFOUR-1-Ni, and its chromate analogue, CROFOUR-1-Ni,
      exhibit high CO(2) affinity and selectivity, especially at low loading. This
      behavior can be attributed to exceptionally high isosteric heats of adsorption
      (Q(st)) of CO(2) in MOOFOUR-1-Ni and CROFOUR-1-Ni of ~56 and ~50 kJ/mol,
      respectively, at zero loading. These results were validated by molecular
      simulations which indicate that the electrostatics of these inorganic anions
      affords attractions toward CO(2) that are comparable to those of unsaturated
      metal centers.

PMID- 23170982
TI  - alpha-Tropomyosin with a D175N or E180G mutation in only one chain differs from
      tropomyosin with mutations in both chains.
AB  - alpha-Tropomyosin (Tm) carrying hypertrophic cardiomyopathy mutation D175N or
      E180G was expressed in Escherichia coli. We have assembled dimers of two
      polypeptide chains in vitro that carry one (alphaalpha*) or two (alpha*alpha*)
      copies of the mutation. We found that the presence of the mutation has little
      effect on dimer assembly, thereby predicting that individuals heterozygous for
      the Tm mutations are likely to express both alphaalpha* and alpha*alpha* Tm.
      Depending on the expression level, the heterodimer may be the predominant form in
      individuals carrying the mutation. Thus, it is important to define differences in
      the properties of Tm molecules carrying one or two copies of the mutation. We
      examined the Tm homo- and heterodimer properties: actin affinity, thermal
      stability, calcium regulation of myosin subfragment 1 binding, and calcium
      regulation of myofibril force. We report that the properties of the heterodimer
      may be similar to those of the wild-type homodimer (actin affinity, thermal
      stability, D175N alphaalpha*), similar to those of the mutant homodimer (calcium
      sensitivity, D175N alphaalpha*), intermediate between the two (actin affinity,
      E180G alphaalpha*), or different from both (thermal stability, E180G
      alphaalpha*). Thus, the properties of the homodimer are not a completely reliable
      guide to the properties of the heterodimer.

PMID- 23170981
TI  - 'Transient' genetic suppression facilitates generation of hexose transporter null
      mutants in Leishmania mexicana.
AB  - The genome of Leishmania mexicana encompasses a cluster of three glucose
      transporter genes designated LmxGT1, LmxGT2 and LmxGT3. Functional and genetic
      studies of a cluster null mutant (Deltalmxgt1-3) have dissected the roles of
      these proteins in Leishmania metabolism and virulence. However, null mutants were
      recovered at very low frequency, and comparative genome hybridizations revealed
      that Deltalmxgt1-3 mutants contained a linear extrachromosomal 40 kb
      amplification of a region on chromosome 29 not amplified in wild type parasites.
      These data suggested a model where this 29-40k amplicon encoded a second site
      suppressor contributing to parasite survival in the absence of GT1-3 function. To
      test this, we quantified the frequency of recovery of knockouts in the presence
      of individual overexpressed open reading frames covering the 29-40k amplicon. The
      data mapped the suppressor activity to PIFTC3, encoding a component of the
      intraflagellar transport pathway. We discuss possible models by which PIFTC3
      might act to facilitate loss of GTs specifically. Surprisingly, by plasmid
      segregation we showed that continued PIFTC3 overexpression was not required for
      Deltalmxgt1-3 viability. These studies provide the first evidence that genetic
      suppression can occur by providing critical biological functions transiently.
      This novel form of genetic suppression may extend to other genes, pathways and
      organisms.

PMID- 23170984
TI  - Heterojunction silicon microwire solar cells.
AB  - We report radial heterojunction solar cells of amorphous silicon on crystalline
      silicon microwires with high surface passivation. While the shortened collection
      path is exploited to increase the photocurrent, proper choice of the wire radius
      and the highly passivated surface prevent drastic decrease in the voltage due to
      high surface-to-volume ratio. The heterojunction is formed by depositing a ~12-16
      nm of amorphous silicon on crystalline silicon wires of radius approximately
      equal to minority carrier diffusion length (~10 MUm). In spite of very short
      carrier lifetime (<1 MUs), the microwire array devices generate photocurrent of
      ~30 mA/cm(2), and the same time, voltages close to 600 mV are achieved, leading
      to efficiency in excess of 12% in extremely short carrier lifetime silicon. We
      also find that formation of nanocrystallites of silicon in the deposited film
      results in loss of the expected passivation.

PMID- 23170985
TI  - Acute hemorrhagic edema of infancy: a troubling cutaneous presentation with a
      self-limiting course.
AB  - Acute hemorrhagic edema of infancy (AHEI) is an unusual form of leukocytoclastic
      vasculitis with dramatic distinguishing skin lesions that occurs in infants ages
      4 to 24 months old. The disease presents with skin eruptions that usually start
      with large (1-5 cm), symmetrically distributed, hemorrhagic lesions in a
      characteristic cockade pattern. The lesions are typically located on the lower
      extremities, face (in particular the ears, cheeks, and eyelids), and gluteal
      area. Fever may accompany skin eruptions. Clinical presentation at onset requires
      clinical and laboratory examination to distinguish it from more serious diseases
      and other vasculitis. The main differential diagnosis of AHEI is Henoch-Schonlein
      purpura. AHEI is generally a self-limiting disease, so a conservative approach
      should be considered. Topical or systemic corticosteroid therapy has been
      reported to be beneficial, as well as antihistamines and dapsone, although AHEI
      usually resolves completely with or without treatment. We report two cases of
      AHEI and an update of the literature. 

PMID- 23170986
TI  - The MSH2 c.388_389del mutation shows a founder effect in Portuguese Lynch
      syndrome families.
AB  - The MSH2 c.388_389del mutation has occasionally been described in Lynch families
      worldwide. At the Portuguese Oncology Institute in Porto, Portugal, we have
      identified 16 seemingly unrelated families with this germline mutation. To
      evaluate if this alteration is a founder or a recurrent mutation we performed
      haplotype analysis in the 16 Portuguese index cases and 55 relatives, as well as
      in four index cases and 13 relatives reported from Germany, Scotland, England,
      and Argentina. In the Portuguese families we observed a shared haplotype of
      approximately 10 Mb and all were originated from the north of Portugal. These
      results suggest that this alteration is a founder mutation in Portugal with a
      relatively recent origin. In the reported families outside Portugal with this
      mutation different haplotype backgrounds were observed, supporting the hypothesis
      that it occurred de novo on multiple occasions. We also conclude that the high
      proportion of families with the MSH2 c.388_389del mutation indicates that
      screening for this alteration as a first step may be cost-effective in the
      genetic testing of Lynch syndrome suspects of Portuguese ancestry, especially
      those originating from the north of Portugal. 

PMID- 23170988
TI  - The alignment of carbon nanotubes: an effective route to extend their excellent
      properties to macroscopic scale.
AB  - To improve the practical application of carbon nanotubes, it is critically
      important to extend their physical properties from the nanoscale to the
      macroscopic scale. Recently, chemists aligned continuous multiwalled carbon
      nanotube (MWCNT) sheets and fibers to produce materials with high mechanical
      strength and electrical conductivity. This provided an important clue to the use
      of MWCNTs at macroscopic scale. Researchers have made multiple efforts to
      optimize this aligned structure and improve the properties of MWCNT sheets and
      fibers. In this Account, we briefly highlight the new synthetic methods and
      promising applications of aligned MWCNTs for organic optoelectronic materials and
      devices.  We describe several general methods to prepare both horizontally and
      perpendicularly aligned MWCNT/polymer composite films, through an easy solution
      or melting process. The composite films exhibit the combined properties of being
      flexible, transparent, and electrically conductive. These advances may pave the
      way to new flexible substrates for organic solar cells, sensing devices, and
      other related applications. Similarly, we discuss the synthesis of aligned
      MWCNT/polymer composite fibers with interesting mechanical and electrical
      properties. Through these methods, we can incorporate a wide variety of soluble
      or fusible polymers for such composite films and fibers.  In addition, we can
      later introduce functional polymers with conjugated backbones or side chains to
      improve the properties of these composite materials. In particular, cooperative
      interactions between aligned MWCNTs and polymers can produce novel properties
      that do not occur individually. Common examples of this are two types of
      responsive polymers, photodeformable azobenzene-containing liquid crystalline
      polymer and chromatic polydiacetylene. Aligning the structure of MWCNTs induces
      the orientation of azobenzene-containing mesogens, and produces photodeformable
      polymer elastomers. This strategy also solves the long-standing problems from the
      traditional mechanical rubbing method, which include production of broken debris
      and structure damage during fabrication and building up electrostatic charge
      during use. Aligning MWCNTs induces a conformational change in polydiacetylene,
      which causes the composite fibers to be electrochromatic, a previously unknown
      reaction in chromatic polymers.  Due to their large surface area, flexibility,
      electrical conductivity, and remarkable electrocatalytic activity, aligned MWCNT
      films can be used as counter electrodes to produce highly efficient dye
      sensitized solar cells. In addition, chemists have developed new electrodes from
      the aligned MWCNT fibers to make a family of high-performing, wire-shaped dye
      sensitized solar cells.

PMID- 23170987
TI  - Individual and environmental factors underlying life space of older people -
      study protocol and design of a cohort study on life-space mobility in old age
      (LISPE).
AB  - BACKGROUND: A crucial issue for the sustainability of societies is how to
      maintain health and functioning in older people. With increasing age, losses in
      vision, hearing, balance, mobility and cognitive capacity render older people
      particularly exposed to environmental barriers. A central building block of human
      functioning is walking. Walking difficulties may start to develop in midlife and
      become increasingly prevalent with age. Life-space mobility reflects actual
      mobility performance by taking into account the balance between older adults
      internal physiologic capacity and the external challenges they encounter in daily
      life. The aim of the Life-Space Mobility in Old Age (LISPE) project is to examine
      how home and neighborhood characteristics influence people's health, functioning,
      disability, quality of life and life-space mobility in the context of aging. In
      addition, examine whether a person's health and function influence life-space
      mobility. DESIGN: This paper describes the study protocol of the LISPE project,
      which is a 2-year prospective cohort study of community-dwelling older people
      aged 75 to 90 (n = 848). The data consists of a baseline survey including face-to
      face interviews, objective observation of the home environment and a physical
      performance test in the participant's home. All the baseline participants will be
      interviewed over the phone one and two years after baseline to collect data on
      life-space mobility, disability and participation restriction. Additional home
      interviews and environmental evaluations will be conducted for those who relocate
      during the study period. Data on mortality and health service use will be
      collected from national registers. In a substudy on walking activity and life
      space, 358 participants kept a 7-day diary and, in addition, 176 participants
      also wore an accelerometer. DISCUSSION: Our study, which includes extensive data
      collection with a large sample, provides a unique opportunity to study topics of
      importance for aging societies. A novel approach is employed which enables us to
      study the interactions of environmental features and individual characteristics
      underlying the life-space of older people. Potentially, the results of this study
      will contribute to improvements in strategies to postpone or prevent progression
      to disability and loss of independence.

PMID- 23170989
TI  - Integrative oncology for breast cancer patients: introduction of an expert-based
      model.
AB  - BACKGROUND: Malignant breast neoplasms are among the most frequent forms of
      cancer in the Western world. Conventional treatment of breast cancer may include
      surgery, hormonal therapy, chemotherapy, radiation and/or immunotherapy, all of
      which are often accompanied by severe side effects. Complementary and alternative
      medicine (CAM) treatments have been shown to be effective in alleviating those
      symptoms. Furthermore, with patient survival rates increasing, oncologists,
      psychologists and other therapists have to become more sensitive to the needs of
      cancer survivors that go beyond than the mere alleviation of symptoms. Many CAM
      methods are geared to treat the patient in a holistic manner and thus are also
      concerned with the patient's psychological and spiritual needs. DISCUSSION: The
      use of certain CAM methods may become problematic when, as frequently occurs,
      patients use them indiscriminately and without informing their oncologists.
      Herbal medicines and dietary supplements, especially, may interfere with primary
      cancer treatments or have other detrimental effects. Thus, expertise in this
      highly specialized field of integrative medicine should be available to patients
      so that they can be advised about the benefits and negative effects of such
      preparations and practices.Being a beneficial combination of conventional and CAM
      care, integrative oncology makes possible the holistic approach to cancer care.
      The concept of integrative oncology for breast cancer is jointly practiced by the
      Department of Internal and Integrative Medicine, Kliniken Essen-Mitte, academic
      teaching hospital of the University of Duisburg-Essen, and the Breast Center at
      Kliniken Essen-Mitte in Germany. This model is introduced here; its scope is
      reviewed, and its possible implications for the practice of integrative medicine
      are discussed. SUMMARY: Evidence-based integrative care is crucial to the field
      of oncology in establishing state-of-the-art care for breast cancer patients.

PMID- 23170990
TI  - A multicentre, multinational, randomized, placebo-controlled, double-blind, phase
      3 trial to evaluate the efficacy and safety of gemigliptin (LC15-0444) in
      patients with type 2 diabetes.
AB  - AIM: This study was designed to assess the efficacy and safety of the dipeptidyl
      peptidase IV inhibitor gemigliptin (LC15-0444) 50 mg versus placebo in patients
      with type 2 diabetes. METHODS: We conducted a 24-week, randomized, double-blind,
      placebo-controlled phase III trial in 182 patients (74 from Korea and 108 from
      India) with type 2 diabetes. After an initial 2 weeks of a diet and exercise
      programme followed by 2 weeks of a single-blind placebo run-in period, eligible
      patients were randomized to gemigliptin 50 mg or placebo, receiving the assigned
      treatment for 24 weeks. HbA1c and fasting plasma glucose (FPG) were measured
      periodically, and oral glucose tolerance test was performed at baseline and weeks
      12 and 24. RESULTS: At week 24, gemigliptin treatment led to significant
      reductions in HbA1c measurements compared to placebo (adjust mean after
      subtracting the placebo effect size: -0.71%, 95% confidence interval: -1.04 to 
      0.37%). A significantly greater proportion of patients achieved an HbA1c <7% with
      gemigliptin than with placebo. The placebo-subtracted FPG change from baseline at
      week 24 was -19.80 mg/dl. The overall incidence rates for adverse events were
      similar in the gemigliptin and placebo groups. CONCLUSIONS: This study showed the
      efficacy and safety of gemigliptin 50 mg administered once daily as a monotherapy
      for type 2 diabetes patients.

PMID- 23170991
TI  - Outcomes of children receiving en bloc renal transplants from small pediatric
      donors.
AB  - The utilization of en bloc renal allografts from small pediatric donors has been
      adopted as an effective strategy to expand the organ donor pool in adult
      recipients. Data in children are limited. The aim of our study is to describe the
      outcomes of en bloc renal transplants in children from our center. Medical
      records of children receiving pediatric en bloc renal transplants at our
      institution from January 2007 were abstracted. Data collected included recipient
      and donor demographics, operative technique and complications, and post-operative
      studies. Eight children received en bloc renal transplants at a median age of 17
      yr; median follow-up was 0.9 yr. Donor body weight ranged from 4 to 22 kg. One
      kidney was lost to intra-operative thrombosis, while the other kidney from this
      en bloc graft remained viable. All grafts showed increased renal size at follow
      up ultrasound. Surveillance biopsies showed glomerulomegaly in two patients. At
      last follow-up, the median eGFR was 130 mL/min/1.73 m(2). The urinary protein to
      creatinine ratio was normal in four of seven patients. Our data suggest that in
      experienced centers, en bloc renal transplantation from young donors into
      pediatric recipients is effective. Long-term follow-up to monitor for
      complications, including hyperfiltration injury, is warranted.

PMID- 23170992
TI  - Cost-effectiveness models of pneumococcal conjugate vaccines: variability and
      impact of modeling assumptions.
AB  - Currently, 13-valent pneumococcal conjugate vaccine (PCV); and ten-valent PCV
      vaccine are marketed. Neither vaccine obtained regulatory approval based on
      efficacy trials, but instead were approved based on a surrogate end point:
      immunogenicity data measuring effective antibody levels. Therefore, direct
      measures of efficacy were unavailable at the time economic analyses were
      conducted. The authors systematically reviewed cost-effectiveness studies of ten
      valent PCV and 13-valent PCV from the literature to analyze the methodologies and
      compare the assumptions made about vaccine effectiveness. The following three
      inputs were found the most variant across analyses: efficacy against acute otitis
      media; inclusion of indirect effects; and cross protection. These assumptions are
      discussed with regard to the validity of supporting data and implications on
      decision-making.

PMID- 23170994
TI  - Peptido sulfonyl fluorides as new powerful proteasome inhibitors.
AB  - A new class of potent proteasome inhibitors is described, of which the members
      contain an amino acid inspired sulfonyl fluoride as the electrophilic trap. In
      total, 24 peptido sulfonyl fluoride inhibitors have been designed and
      synthesized, which were inspired by the backbone sequences of the proteasome
      inhibitors bortezomib, epoxomicin, and Cbz-Leu(3)-aldehyde. Nine of them were
      very potent proteasome inhibitors, the best of which had an IC(50) of 7 nM. A
      number of the peptido sulfonyl fluoride inhibitors were found to be highly
      selective for the beta5 proteasome subunit.

PMID- 23170993
TI  - Impact of animal-assisted therapy for outpatients with fibromyalgia.
AB  - OBJECTIVES: Animal-assisted therapy using dogs trained to be calm and provide
      comfort to strangers has been used as a complementary therapy for a range of
      medical conditions. This study was designed to evaluate the effects of brief
      therapy dog visits for fibromyalgia patients attending a tertiary outpatient pain
      management facility compared with time spent in a waiting room. DESIGN: Open
      label with waiting room control. SETTING: Tertiary care, university-based,
      outpatient pain management clinic. SUBJECTS: A convenience sample of fibromyalgia
      patients was obtained through advertisements posted in the clinic. INTERVENTIONS:
      Participants were able to spend clinic waiting time with a certified therapy dog
      instead of waiting in the outpatient waiting area. When the therapy dog was not
      available, individuals remained in the waiting area. OUTCOME MEASURES.: Self
      reported pain, fatigue, and emotional distress were recorded using 11-point
      numeric rating scales before and after the therapy dog visit or waiting room
      time. RESULTS: Data were evaluated from 106 therapy dog visits and 49 waiting
      room controls, with no significant between-group demographic differences in
      participants. Average intervention duration was 12 minutes for the therapy dog
      visit and 17 minutes for the waiting room control. Significant improvements were
      reported for pain, mood, and other measures of distress among patients after the
      therapy dog visit, but not the waiting room control. Clinically meaningful pain
      relief (>=2 points pain severity reduction) occurred in 34% after the therapy dog
      visit and 4% in the waiting room control. Outcome was not affected by the
      presence of comorbid anxiety or depression. CONCLUSIONS: Brief therapy dog visits
      may provide a valuable complementary therapy for fibromyalgia outpatients.

PMID- 23170995
TI  - Eccrine squamous syringometaplasia secondary to cutaneous extravasation of
      docetaxel: report of three cases.
AB  - Eccrine squamous syringometaplasia is characterized by the metaplasia of cuboidal
      epithelial cells of the eccrine sweat ducts into squamous epithelial cells. It
      has been associated with several conditions including chemotherapy-related
      bilateral dermatitis, an entity that can take place in body areas rich in eccrine
      glands, as well as in acral erythema related to chemotherapy. Only a few cases
      because of cutaneous extravasation of chemotherapy have been previously reported.
      We report three cases of eccrine squamous syringometaplasia secondary to
      extravasation of docetaxel. 

PMID- 23170996
TI  - Development of Zn-related necrosis in tobacco is enhanced by expressing AtHMA4
      and depends on the apoplastic Zn levels.
AB  - AtHMA4 was previously shown to contribute to the control of Zn root-to-shoot
      translocation and tolerance to high Zn. However, heterologous expression of
      35S::AtHMA4 in tobacco (Nicotiana tabacum cv. Xanthi) results in enhanced Zn
      sensitivity. This study provides a better understanding of the development of
      this Zn-sensitive phenotype and demonstrates that substantial modifications of Zn
      homeostasis occur due to AtHMA4 expression. We show that ectopically expressing
      AtHMA4 in tobacco results in overloading the root and leaf apoplast with Zn. The
      tissue and cellular distribution of Zn, monitored using Zinpyr-1, was altered in
      the AtHMA4-expressing plants compared with wild type. Increased loading of the
      leaf apoplast with Zn in AtHMA4 transformants induced necrosis; this appeared at
      lower levels of Zn supply in the transgenics compared with wild type. This study
      suggests that Zn concentration may be sensed in the apoplast of leaves, and if
      concentrations are above a certain threshold then particular groups of cells
      accumulate Zn and necrosis is initiated. Therefore, this could be considered as a
      mechanism for protecting the other parts of the photosynthetically active leaf
      from Zn toxicity.

PMID- 23170997
TI  - Erectile dysfunction precedes coronary artery endothelial dysfunction in rats fed
      a high-fat, high-sucrose, Western pattern diet.
AB  - Introduction.  It is suggested that erectile dysfunction (ED) may be an early
      risk factor for cardiovascular disease. Aim.  The goal of this study was to
      determine whether development of ED precedes the onset of coronary artery
      endothelial dysfunction in response to a Western diet (WD), thereby establishing
      whether the WD differentially impacts the endothelium in a time-dependent manner.
      Additionally, a goal was to determine if diet-induced ED is reversible with
      intracavernosal sepiapterin treatment. Methods.  Male Sprague-Dawley rats were
      fed a WD for 4, 8, or 12 weeks, or a control diet for 8 weeks. Erectile function
      was evaluated by measuring the mean arterial pressure (MAP) and intracavernosal
      pressure (ICP) in response to electrical field stimulation of the cavernosal
      nerve near the major pelvic ganglion, in the absence and presence of sepiapterin.
      Coronary artery endothelial function was evaluated ex vivo with cumulative doses
      of acetylcholine (ACh) applied to segments of the left anterior descending
      coronary artery preconstricted with serotonin. Main Outcome Measures.  Erectile
      function was assessed as the ICP response to electrical field stimulation (EFS),
      normalized to MAP. Coronary artery endothelial function was assessed as the
      effective concentration producing 50% of a maximal response (EC50 ) of the ACh
      response. Results.  The ICP/MAP response to EFS was significantly attenuated
      following both 8 and 12 weeks of the WD compared with the control diet (P <
      0.05). Sepiapterin treatment augmented the ICP/MAP response in all WD groups (P <
      0.05). The coronary artery EC50 of the ACh response was not different from
      control following 4 or 8 weeks but was significantly elevated following 12 weeks
      of the WD (P < 0.01). Conclusions.  These data suggest that erectile function is
      reduced prior to coronary artery endothelial function in response to the WD.
      Improvement of erectile function with sepiapterin in WD rats indicates that
      nitric oxide synthase uncoupling is a key mechanism in diet-induced ED. La Favor
      JD, Anderson EJ, Hickner RC, and Wingard CJ. Erectile dysfunction precedes
      coronary artery endothelial dysfunction in rats fed a high-fat, high-sucrose,
      Western pattern diet. J Sex Med 2013;10:694-703.

PMID- 23170998
TI  - Impact of 4 Lactobacillus plantarum capsular polysaccharide clusters on surface
      glycan composition and host cell signaling.
AB  - BACKGROUND: Bacterial cell surface-associated polysaccharides are involved in the
      interactions of bacteria with their environment and play an important role in the
      communication between pathogenic bacteria and their host organisms. Cell surface
      polysaccharides of probiotic species are far less well described. Therefore,
      improved knowledge on these molecules is potentially of great importance to
      understand the strain-specific and proposed beneficial modes of probiotic action.
      RESULTS: The Lactobacillus plantarum WCFS1 genome encodes 4 clusters of genes
      that are associated with surface polysaccharide production. Two of these clusters
      appear to encode all functions required for capsular polysaccharide formation
      (cps2A-J and cps4A-J), while the remaining clusters are predicted to lack genes
      encoding chain-length control functions and a priming glycosyl-transferase (cps1A
      I and cps3A-J). We constructed L. plantarum WCFS1 gene deletion mutants that lack
      individual (Deltacps1A-I, Deltacps2A-J, Deltacps3A-J and Deltacps4A-J) or
      combinations of cps clusters (Deltacps1A-3J and Deltacps1A-3I, Deltacps4A-J) and
      assessed the genome wide impact of these mutations by transcriptome analysis. The
      cps cluster deletions influenced the expression of variable gene sets in the
      individual cps cluster mutants, but also considerable numbers of up- and down
      regulated genes were shared between mutants in cps cluster 1 and 2, as well as
      between mutant in cps clusters 3 and 4. Additionally, the composition of overall
      cell surface polysaccharide fractions was altered in each mutant strain, implying
      that despite the apparent incompleteness of cps1A-I and cps3A-J, all clusters are
      active and functional in L. plantarum. The Deltacps1A-I strain produced surface
      polysaccharides in equal amounts as compared to the wild-type strain, while the
      polysaccharides were characterized by a reduced molar mass and the lack of
      rhamnose. The mutants that lacked functional copies of cps2A-J, cps3A-J or cps4A
      J produced decreased levels of surface polysaccharides, whereas the molar mass
      and the composition of polysaccharides was not affected by these cluster
      mutations. In the quadruple mutant, the amount of surface polysaccharides was
      strongly reduced. The impact of the cps cluster mutations on toll-like receptor
      (TLR)-mediated human nuclear factor (NF)-kappaB activation in host cells was
      evaluated using a TLR2 reporter cell line. In comparison to a L. plantarum wild
      type derivative, TLR2 activation remained unaffected by the Deltacps1A-I and
      Deltacps3A-J mutants but appeared slightly increased after stimulation with the
      Deltacps2A-J and Deltacps4A-J mutants, while the Deltacps1A-3J and Deltacps1A-3J,
      Deltacps4A-J mutants elicited the strongest responses and clearly displayed
      enhanced TLR2 signaling. CONCLUSIONS: Our study reveals that modulation of
      surface glycan characteristics in L. plantarum highlights the role of these
      molecules in shielding of cell envelope embedded host receptor ligands. Although
      the apparently complete cps clusters (cps2A-J and cps4A-J) contributed
      individually to this shielding, the removal of all cps clusters led to the
      strongest signaling enhancement. Our findings provide new insights into cell
      surface glycan biosynthesis in L. plantarum, which bears relevance in the context
      of host-cell signaling by probiotic bacteria.

PMID- 23170999
TI  - Mapping the chemistry of resinite, funginite and associated vitrinite in coal
      with micro-FTIR.
AB  - Micro-FTIR mapping is a powerful tool for nondestructive, in situ chemical
      characterization of coal macerals at high resolution. In this study, the
      chemistry of resinite, funginite and associated vitrinite is characterized via
      reflectance micro-FTIR for Cenozoic high volatile C bituminous coals from
      Colombia. In comparison with the micro-FTIR spectra of vitrinite and inertinite,
      the corresponding spectra of liptinite macerals in the same coals are
      characterized by stronger aliphatic CH(x) absorbance at 3000-2800 and 1460-1450
      cm-1, but less intense aromatic C=C ring stretching vibration and aromatic CH(x)
      out-of-plane deformation at 700-900 cm-1. The aliphatic components in resinite
      have the longest carbon chains and are least branched, bestowing the highest
      hydrocarbon generation potential on resinite among the three macerals studied. In
      contrast, funginite exhibits the strongest aromatic character, the highest
      aromaticity, the lowest 'A' factor values and the lowest C=O/C=C ratios among the
      three maceral groups. Vitrinite generally displays intermediate chemical
      characteristics. Reflectance micro-FTIR mapping of coal samples further confirms
      the aliphatic character of resinite and the aromatic nature of funginite. In
      addition, chemical mapping of resinite and adjacent vitrinite shows that
      vitrinite immediately adjacent to resinite displays higher aliphatic CH(x)
      stretching intensity than more distant vitrinite, suggesting that chemical
      components from resinite can diffuse over short distances into adjacent
      vitrinite, specifically causing hydrogen enrichment. It needs to be pointed out,
      however, that the region of influence is localized and limited to a narrow zone,
      whose extent likely depends on resinite's properties, such as its size and
      aliphatic material content. This way, the chemical map of resinite and associated
      vitrinite provides direct evidence of the intermaceral effects occurring during
      the peat forming stage or during later coalification. No influence of funginite
      (primarily fungal spores and sclerotia) on the chemistry of adjacent vitrinite
      has been demonstrated, which is likely due to the highly aromatic structure of
      this type of funginite.

PMID- 23171000
TI  - Automatic design of decision-tree induction algorithms tailored to flexible
      receptor docking data.
AB  - BACKGROUND: This paper addresses the prediction of the free energy of binding of
      a drug candidate with enzyme InhA associated with Mycobacterium tuberculosis.
      This problem is found within rational drug design, where interactions between
      drug candidates and target proteins are verified through molecular docking
      simulations. In this application, it is important not only to correctly predict
      the free energy of binding, but also to provide a comprehensible model that could
      be validated by a domain specialist. Decision-tree induction algorithms have been
      successfully used in drug-design related applications, specially considering that
      decision trees are simple to understand, interpret, and validate. There are
      several decision-tree induction algorithms available for general-use, but each
      one has a bias that makes it more suitable for a particular data distribution. In
      this article, we propose and investigate the automatic design of decision-tree
      induction algorithms tailored to particular drug-enzyme binding data sets. We
      investigate the performance of our new method for evaluating binding
      conformations of different drug candidates to InhA, and we analyze our findings
      with respect to decision tree accuracy, comprehensibility, and biological
      relevance. RESULTS: The empirical analysis indicates that our method is capable
      of automatically generating decision-tree induction algorithms that significantly
      outperform the traditional C4.5 algorithm with respect to both accuracy and
      comprehensibility. In addition, we provide the biological interpretation of the
      rules generated by our approach, reinforcing the importance of comprehensible
      predictive models in this particular bioinformatics application. CONCLUSIONS: We
      conclude that automatically designing a decision-tree algorithm tailored to
      molecular docking data is a promising alternative for the prediction of the free
      energy from the binding of a drug candidate with a flexible-receptor.

PMID- 23171002
TI  - Rotation flap approach mastectomy.
AB  - BACKGROUND: The authors present a technique for mastectomy with greater
      versatility for reconstruction. METHODS: The areola is marked and a vertical line
      is dropped medial to the breast axis, down towards the inframammary fold and
      laterally to the anterior axillary line. In large ptotic breasts, the markings
      are modified to reduce the skin envelope. The rotation flap is raised over the
      lateral half of the breast, and the remainder of the skin envelope is then
      separated from the breast tissue as per any other mastectomy. Skin closure is by
      rotation of the flap and incremental gathering of skin. An audit of 37 cases of
      rotation flap approach (RoFA) mastectomy has been performed, evaluating
      complications and post-reconstruction outcome using the BREAST Q. RESULTS: RoFA
      has been found to offer good access for mastectomy and lymphadenectomy. A total
      of 7 of 37 patients had delay in healing, and 2 patients developed haematoma.
      Post-reconstruction outcome was scored as comparable with other published series.
      DISCUSSION: The RoFA mastectomy has the potential to facilitate reconstructive
      results equivalent to skin-sparing mastectomy and immediate reconstruction.

PMID- 23171001
TI  - Small RNA and transcriptome deep sequencing proffers insight into floral gene
      regulation  in Rosa cultivars.
AB  - BACKGROUND: Roses (Rosa sp.), which belong to the family Rosaceae, are the most
      economically important ornamental plants--making up 30% of the floriculture
      market. However, given high demand for roses, rose breeding programs are limited
      in molecular resources which can greatly enhance and speed breeding efforts. A
      better understanding of important genes that contribute to important floral
      development and desired phenotypes will lead to improved rose cultivars. For this
      study, we analyzed rose miRNAs and the rose flower transcriptome in order to
      generate a database to expound upon current knowledge regarding regulation of
      important floral characteristics. A rose genetic database will enable
      comprehensive analysis of gene expression and regulation via miRNA among
      different Rosa cultivars. RESULTS: We produced more than 0.5 million reads from
      expressed sequences, totalling more than 110 million bp. From these, we generated
      35,657, 31,434, 34,725, and 39,722 flower unigenes from Rosa hybrid: 'Vital',
      'Maroussia', and 'Sympathy' and Rosa rugosa Thunb., respectively. The unigenes
      were assigned functional annotations, domains, metabolic pathways, Gene Ontology
      (GO) terms, Plant Ontology (PO) terms, and MIPS Functional Catalogue (FunCat)
      terms. Rose flower transcripts were compared with genes from whole genome
      sequences of Rosaceae members (apple, strawberry, and peach) and grape. We also
      produced approximately 40 million small RNA reads from flower tissue for Rosa,
      representing 267 unique miRNA tags. Among identified miRNAs, 25 of them were
      novel and 242 of them were conserved miRNAs. Statistical analyses of miRNA
      profiles revealed both shared and species-specific miRNAs, which presumably
      effect flower development and phenotypes. CONCLUSIONS: In this study, we
      constructed a Rose miRNA and transcriptome database, and we analyzed the miRNAs
      and transcriptome generated from the flower tissues of four Rosa cultivars. The
      database provides a comprehensive genetic resource which can be used to better
      understand rose flower development and to identify candidate genes for important
      phenotypes.

PMID- 23171003
TI  - Association of genetic variations in GNB1 with response to peginterferon plus
      ribavirin therapy for chronic hepatitis C in a Chinese population in Taiwan.
AB  - BACKGROUND: The aim of this study was to evaluate whether polymorphisms in the
      guanine nucleotide binding (G protein), beta polypeptide 1 (GNB1) gene are
      associated with a rapid virological response (RVR) among HCV genotype 1 (HCV-1)
      and 2 (HCV-2) infected patients receiving peginterferon plus ribavirin treatment
      (PEG-IFNalpha-RBV). METHODS: We analyzed the association between RVR to PEG
      IFNalpha-RBV therapy and 4 tagging single nucleotide polymorphisms (SNPs) of the
      GNB1 gene. This study included 265 HCV-1 and 195 HCV-2 infected patients in a
      Chinese population in Taiwan. RESULTS: Among the GNB1 SNPs examined, the
      combination of genotypes G/G and G/T populations of rs12126768 was significant
      inversely correlated with RVR in HCV-1 infected patients (P = 0.0330), whereas
      HCV-2 infected patients, combination of A/A and A/C genotypes populations at
      rs4648727 responded better to the PEG-IFNalpha-RBV treatment (P = 0.0089).
      However, there were no significant differences in the allele frequencies of those
      SNPs between RVR responders and non-responders. Several RVR susceptibility GNB1
      haplotypes were identified, and the ACAT haplotype of the 4 SNPs may increase the
      successful outcomes of HCV-1 and HCV-2 infected patients (P = 0.0261 and P =
      0.0253, respectively). CONCLUSION: The data for GNB1 SNPs and the association of
      RVR showed that GNB1 polymorphisms might be associated with the therapeutic
      outcomes of HCV-1 and HCV-2 infected patients under standard of care (SOC)
      treatment.

PMID- 23171004
TI  - A new ovarian response prediction index (ORPI): implications for individualised
      controlled ovarian stimulation.
AB  - BACKGROUND: The objective was to present a new ovarian response prediction index
      (ORPI), which was based on anti-Mullerian hormone (AMH) levels, antral follicle
      count (AFC) and age, and to verify whether it could be a reliable predictor of
      the ovarian stimulation response. METHODS: A total of 101 patients enrolled in
      the ICSI programme were included. The ORPI values were calculated by multiplying
      the AMH level (ng/ml) by the number of antral follicles (2-9 mm), and the result
      was divided by the age (years) of the patient (ORPI=(AMH x AFC)/Patient age).
      RESULTS: The regression analysis demonstrated significant (P<0.0001) positive
      correlations between the ORPI and the total number of oocytes and of MII oocytes
      collected. The logistic regression revealed that the ORPI values were
      significantly associated with the likelihood of pregnancy (odds ratio (OR): 1.86;
      P=0.006) and collecting greater than or equal to 4 oocytes (OR: 49.25; P<0.0001),
      greater than or equal to 4 MII oocytes (OR: 6.26; P<0.0001) and greater than or
      equal to 15 oocytes (OR: 6.10; P<0.0001). Regarding the probability of collecting
      greater than or equal to 4 oocytes according to the ORPI value, the ROC curve
      showed an area under the curve (AUC) of 0.91 and an efficacy of 88% at a cut-off
      of 0.2. In relation to the probability of collecting greater than or equal to 4
      MII oocytes according to the ORPI value, the ROC curve had an AUC of 0.84 and an
      efficacy of 81% at a cut-off of 0.3. The ROC curve for the probability of
      collecting greater than or equal to 15 oocytes resulted in an AUC of 0.89 and an
      efficacy of 82% at a cut-off of 0.9. Finally, regarding the probability of
      pregnancy occurrence according to the ORPI value, the ROC curve showed an AUC of
      0.74 and an efficacy of 62% at a cut-off of 0.3. CONCLUSIONS: The ORPI exhibited
      an excellent ability to predict a low ovarian response and a good ability to
      predict a collection of greater than or equal to 4 MII oocytes, an excessive
      ovarian response and the occurrence of pregnancy in infertile women. The ORPI
      might be used to improve the cost-benefit ratio of ovarian stimulation regimens
      by guiding the selection of medications and by modulating the doses and regimens
      according to the actual needs of the patients.

PMID- 23171006
TI  - Skin manifestations of nutritional deficiency disease in children: modern day
      contexts.
AB  - Nutritional deficiency syndromes, such as scurvy, pellagra, and beriberi are of
      historical significance but have largely disappeared from modern society.
      However, certain populations of children in modern society are at risk of severe
      nutritional complications. The rarity of these syndromes and lack of
      understanding about modern-day risk factors for nutritional deficiency often
      delays diagnosis. Dermatologists must maintain an appropriate index of suspicion
      for these characteristic syndromes as many of the deficiency states present with
      cutaneous manifestations. Here we review the cutaneous manifestations of
      macronutrient and micronutrient deficiency syndromes as well as those populations
      of children that remain at risk for developing severe disease.

PMID- 23171007
TI  - Aplasia cutis congenita with fetus papyraceus: report and review of the
      literature.
AB  - We report a case of a 2-week-old white female who presented with large stellate
      atrophic skin defects on bilateral thighs and knees at birth. The pregnancy was
      complicated by the death of monozygotic twin at the 16th week of gestation. This
      represents aplasia cutis congenita with fetus papyraceus. This rare condition is
      defined as the congenital skin defect and intrauterine death of fetus with or
      without a stillborn fetus pressed flat by the growing twin (fetus papyraceus) at
      delivery time. Aplasia cutis congenita coexisting with fetus papyraceus has a
      distinctive and reproducible distribution pattern of bilateral symmetrical
      truncal, buttock, and thigh lesions related to fetal death during the late first
      to early second trimester. There are at least 44 reported cases of this disorder
      in the English literature. We discuss our case and review the literature.

PMID- 23171005
TI  - Properties of membrane-incorporated WALP peptides that are anchored on only one
      end.
AB  - Peptides of the "WALP" family, acetyl-GWW(LA)(n)LWWA-[ethanol]amide, have proven
      to be opportune models for investigating lipid-peptide interactions. Because the
      average orientations and motional behavior of the N- and C-terminal Trp (W)
      residues differ, it is of interest to investigate how the positions of the
      tryptophans influence the properties of the membrane-incorporated peptides. To
      address this question, we synthesized acetyl-GGWW(LA)(n)-ethanolamide and acetyl
      (AL)(n)WWG-ethanolamide, in which n = 4 or 8, which we designate as "N-anchored"
      and "C-anchored" peptides, respectively. Selected (2)H or (15)N labels were
      incorporated for solid-state nuclear magnetic resonance (NMR) spectroscopy. These
      peptides can be considered "half"-anchored WALP peptides, having only one pair of
      interfacial Trp residues near either the amino or the carboxyl terminus. The
      hydrophobic lengths of the (n = 8) peptides are similar to that of WALP23. These
      longer half-anchored WALP peptides incorporate into lipid bilayers as alpha
      helices, as reflected in their circular dichroism spectra. Solid-state NMR
      experiments indicate that the longer peptide helices assume defined transmembrane
      orientations with small non-zero average tilt angles and moderate to high dynamic
      averaging in bilayer membranes of 1,2-dioleoylphosphatidylcholine, 1,2
      dimyristoylphosphatidylcholine, and 1,2-dilauroylphosphatidylcholine. The
      intrinsically small apparent tilt angles suggest that interactions of aromatic
      residues with lipid headgroups may play an important role in determining the
      magnitude of the peptide tilt in the bilayer membrane. The shorter (n = 4)
      peptides, in stark contrast to the longer peptides, display NMR spectra that are
      characteristic of greatly reduced motional averaging, probably because of peptide
      aggregation in the bilayer environment, and CD spectra that are characteristic of
      beta-structure.

PMID- 23171008
TI  - Solitary nodule on the auricle.

PMID- 23171009
TI  - Blistering eruption on the chest of a 30-year-old pregnant woman.

PMID- 23171010
TI  - Economic burden of moderate to severe plaque psoriasis in Canada.
AB  - BACKGROUND: Psoriasis is a chronic debilitating disease affecting approximately
      one million Canadians. The objective of this study is to estimate the economic
      burden in $CDN (2008) of moderate to severe plaque psoriasis among Canadian
      adults. METHODS: Using a cross-sectional design, direct resource use, costs, lost
      productivity, and quality of life were obtained for 90 subjects diagnosed with
      psoriasis in three dermatology clinics in British Columbia, Ontario, and Quebec.
      An Excel-based economic model was developed to project the annual cost of
      psoriasis, from the societal perspective. RESULTS: The estimated mean annual cost
      of psoriasis was $7999/subject (95% CI: $3563-$12,434) with direct costs
      accounting for 57%. Mean lost productivity costs, which accounted for 43% of the
      mean annual costs of psoriasis, were $3442/subject (95% CI: $1293-$5590).
      CONCLUSION: Projecting the mean costs per patient to the afflicted population
      yields an estimated total annual cost of $1.7 billion (95% CI: $0.8-$2.6 billion)
      attributable to moderate to severe psoriasis in Canada. Understanding the
      interplay between direct costs, lost productivity, and quality of life is
      critical for accurately identifying and evaluating effective treatments for this
      disease.

PMID- 23171011
TI  - Positivity for HLA DR1 is associated with basal cell carcinoma in renal
      transplant patients in southern Brazil.
AB  - BACKGROUND: Renal transplant patients have a higher incidence of non-melanoma
      skin cancer (NMSC). Previous studies hypothesized that human leukocyte antigen
      (HLA), especially types DR1, DR4, and DR7, may influence the incidence of these
      tumors. This study investigates the association between NMSC and the presence of
      HLA DR1, DR4, and DR7 in renal transplant patients in southern Brazil. METHODS:
      In a historical cohort study, 1032 patients who underwent renal transplantation
      during the period from January 1993 to December 2006 were examined to identify
      occurrences of NMSC and HLA status prior to transplant. RESULTS: Of the 1032
      patients examined, 59 (5.71%) developed NMSC (squamous cell carcinoma [SCC]:
      2.42%; basal cell carcinoma [BCC]: 1.74%; both: 1.55%). The presence of HLA DR1
      was associated with a higher probability of developing any NMSC and particularly
      with developing BCC (P < 0.05). There was no statistically significant
      association between the presence of HLA DR4 or DR7 and the occurrence of NMSC in
      this sample. CONCLUSIONS: HLA DR1 appears to be associated with the development
      of BCC, as well as with the higher number of NMSC lesions in renal transplant
      patients. This study supports the trend to associate the DR1 allele with BCC and
      not with SCC.

PMID- 23171012
TI  - The risk of developing non-melanoma skin cancer, lymphoma and melanoma in
      patients with psoriasis in Taiwan: a 10-year, population-based cohort study.
AB  - BACKGROUND: Hospitalized psoriasis patients are known to have a higher risk of
      malignancy (e.g., nonmelanoma skin cancer [NMSC], lymphoma, and melanoma) than
      the general population; currently, it is unclear whether this risk is affected by
      psoriasis severity. The aim of this study was to compare the cancer risk of
      patients with mild and severe psoriasis and the general population. METHODS: Data
      for this retrospective population-based cohort study were obtained from the
      Taiwan National Health Insurance Research Database. This study included 7061
      patients with a first-time diagnosis of psoriasis. All study individuals were
      followed up until the end of 2007. The crude incidence density ratio and
      standardized incidence ratio (SIR) of NMSC, melanoma, and lymphoma were
      determined. RESULTS: Among psoriasis patients, the most common cancer was NMSC
      (density ratio: 7.5); women were at a higher risk of NMSC than men (density
      ratios: 8.08 vs. 7.0). Psoriasis patients in the south geographic group or in the
      50- to 59-year-old age group were most likely to develop NMSC. The NMSC SIR was
      higher among patients with severe psoriasis than among patients with mild
      psoriasis (SIR: 3.72 vs. 7.08). The lymphoma and melanoma SIR among patients with
      severe psoriasis was also high (lymphoma SIR: 4.85; melanoma: 11.01).
      CONCLUSIONS: Psoriasis carries an elevated risk of NMSC and lymphoma. This effect
      is modified by the severity of psoriasis, age, gender, and geographic location.

PMID- 23171013
TI  - Onychomycosis in Cameroon: a clinical and epidemiological study among
      dermatological patients.
AB  - BACKGROUND: There are currently no studies on epidemiology and clinical aspects
      of nail fungal infections in the general population of Cameroon. PATIENTS AND
      METHODS: Two series of patients observed at a hospital dermatological service of
      Yaounde and in a volunteer service of Douala were evaluated. All the patients,
      regardless of the reason for the consultation, were examined by an expert
      dermatologist to discover signs of onychomycosis. Patients with suspected nail
      lesions underwent mycological examination according to the standard techniques.
      RESULTS: Among 590 subjects (317 males and 273 females), aged 16-83 years,
      onychomycosis was mycologically confirmed in 52 cases (8.8%). The infection was
      most common in the fifth decade. Fingernails were affected in 12 cases, toenails
      in 30 cases, and both fingernails and toenails in 10 cases. Dermatophytes were
      isolated in 57.7% of cases, the most common species being Trichophyton rubrum (16
      cases) and Trichophyton violaceum (eight cases). Non-dermatophytic mould,
      including Aspergillus spp., Fusarium spp., and Neoscytalidium dimidiatum, was
      found in 10 cases. Onychomycosis was more common in patients from low social
      economic classes. CONCLUSIONS: This is the first investigation dealing with
      onychomycosis in Cameroon. These data may be useful for future research and in
      the development of preventive and educational strategies.

PMID- 23171014
TI  - Disseminated dermatophytic pseudomycetoma caused by Microsporum species.
AB  - BACKGROUND: Dermatophyte infection is almost exclusively a superficial cutaneous
      mycosis usually confined to the stratum corneum of nails and hairs of normal
      hosts. Deep cutaneous and subcutaneous infections due to dermatophytes are
      exceedingly rare and usually limited to immunosuppressed individuals. These
      infections remain chronic and persist in spite of treatment. MATERIALS AND
      METHODS: We report two clinical cases of disseminated dermatophytic
      pseudomycetoma caused by Microsporum gypseum and Microsporum canis in
      immunosuppressed patients. RESULTS: Patient 1, in 2008, showed improvement with
      fluconazole, cephalothin, and terbinafine treatment for Microsporum gypseum.
      After suspension of the treatment, new lesions appeared and culture from material
      was positive. In 2009, she presented confluent papules and nodules forming
      plaques on her face and neck with the isolation of Microsporum canis. Clinical
      response to this treatment was poor. Patient 2 was affected by both tinea
      corporis due to Trichophyton rubrum and dermatophytic pseudomycetoma caused by
      Microsporum canis. The response to treatment was successful with oral
      itraconazole and local surgical excision. CONCLUSIONS: It is important to
      recognize these atypical presentations of dermatophytic infections in
      immunosuppressed patients, which may warrant a more aggressive treatment in order
      to achieve resolution.

PMID- 23171015
TI  - Post-filarial cutaneous aspergillosis.
AB  - BACKGROUND: Aspergillus species are widely distributed in nature; however,
      cutaneous infections due to A. terreus are particularly rare. In this report, we
      describe a very uncommon case of primary cutaneous aspergillosis presenting as
      cauliflower-like skin lesions caused by A. terreus in a patient with preexisting
      bilateral filarial elephantiasis of the legs. MATERIALS AND METHODS:
      Histopathological examination of the lesions revealed narrow, septate, branching,
      acute-angled hyphae with delicate chitinous walls and multinucleated giant cells
      in the dermis. RESULTS: The fungal isolate was identified as A. terreus using
      standard laboratory procedures. CONCLUSION: Here we report an extremely rare and
      unusual manifestation of primary cutaneous aspergillosis.

PMID- 23171016
TI  - A case of elastosis perforans serpiginosa treatment with cryotherapy.

PMID- 23171017
TI  - Cowden syndrome: review and report of a case of late diagnosis.

PMID- 23171018
TI  - A further case of subacute prurigo-like linear IgA bullous dermatosis: growing
      evidence of a new subset.

PMID- 23171019
TI  - The treatment of keloids with pneumatic technology: a pilot study.
AB  - BACKGROUND: Keloid scars derive from abnormal fibrous wound healing when the
      mechanisms controlling tissue repair and regeneration malfunction. Previous
      studies have reported a reduction in hyaluronic acid among fibroblasts cultured
      from keloid tissue compared with the levels in normal skin. Here, we evaluated
      the efficacy and safety of subdermal minimal surgery using hyaluronic acid as a
      novel treatment in keloid scars. OBJECTIVE: To evaluate the clinical efficacy and
      safety of subdermal minimal surgery technology in the treatment of keloids.
      MATERIALS AND METHODS: Ten Korean patients (Fitzpatrick skin type II-IV) with
      keloids on the upper arms were enrolled in this study. All patients underwent
      three sessions of subdermal minimal surgery at three-week intervals. Scar
      assessments were performed at baseline, before each treatment session, and three
      months after the final treatment, with three different assessment methods.
      Specifically, in addition to the Vancouver Scar Scale (VSS), two independent
      physicians performed global assessment evaluations regarding the final cosmetic
      results. As a final form of assessment, participant satisfaction was assessed
      using a four-point scale. RESULTS: All volunteers completed three treatment
      sessions, and nine of 10 patients were satisfied with the procedure. The average
      VSS score decreased three months after the final treatment, and global assessment
      showed clinical improvement of the scars. No adverse events occurred, except
      transient spot bleeding at entry points and slight post-procedure edema, which
      resolved within 48 hours. CONCLUSION: Subdermal minimal surgery technology may
      help to improve keloids on the upper arm without noticeable adverse effects.

PMID- 23171020
TI  - Both combined oral azithromycin plus allopurinol and intramuscular Glucantime
      yield low efficacy in the treatment of Old World cutaneous leishmaniasis: a
      randomized controlled clinical trial.
AB  - Old World cutaneous leishmaniasis (OWCL) is an endemic and major health problem
      in Iran. The optimal treatment of OWCL is unknown, and current treatments are not
      ideally effective and have many adverse effects. To compare the efficacy and
      tolerability of combined oral azithromycin and allopurinol with intramuscular
      Glucantime in the treatment of OWCL, we conducted a prospective randomized
      clinical trial. A total of 86 patients with OWCL were assigned and divided
      randomly into two groups; they received a combination of azithromycin capsule 10
      mg/kg/d and allopurinol tablet 10 mg/kg/d for two months or IM injection of
      Glucantime 20 mg/kg of antimony daily for 20 days. All patients were followed for
      two months after termination of treatment. Although immediately at the end of the
      treatment period, complete response was seen in 27.8% of patients on combination
      therapy vs. 0% in the Glucantime group. The combination of azithromycin and
      allopurinol had a better outcome; two months after the end of the treatment
      period, complete, partial, and no responses were seen in 38.9%, 22.2%, and 38.9%
      in combination therapy and 40%, 31.4%, and 28.6% in the Glucantime group. There
      was no significant difference between the response rate in both groups after two
      months (P = 0.5). No severe adverse effect occurred. This study demonstrated that
      the efficacy of combined oral azithromycin and allopurinol at the above doses and
      duration was similar to that of IM Glucantime in the treatment of OWCL.

PMID- 23171021
TI  - Prolonged cyclosporine treatment of severe or recalcitrant psoriasis: descriptive
      study in a series of 20 patients.
AB  - BACKGROUND: Although long-term cyclosporine administration may induce toxic
      effects, it may be the only option for the treatment of severe psoriasis. The
      objective of the present study was to retrospectively evaluate efficacy and
      safety of long-term cyclosporine treatment in a cohort of patients affected with
      moderate to severe psoriasis, recalcitrant or unresponsive to other treatments.
      Possible risk factors predicting an intolerance to cyclosporine were also
      investigated. MATERIALS AND METHODS: Data were collected on psoriatic patients
      treated with cyclosporine for at least six months at our Psoriasis Outpatient
      Unit between January 2005 and September 2010. The primary measure for clinical
      efficacy was the PASI 75 response. Cyclosporine safety was assessed through the
      review of both laboratory tests and the adverse events registered during the
      treatment. RESULTS: Twenty patients affected with plaque or erythrodermic
      psoriasis were evaluated. At Week 16, the PASI 75 response was achieved by 85% of
      patients. Adverse events occurred in eight patients (40%): four experienced an
      increase in serum creatinine levels to more than 30% of their pre-treatment
      values and four developed hypertension. Among these patients, five discontinued
      cyclosporine. Side effects resolved after stopping treatment. CONCLUSIONS: Our
      findings suggest that long-term cyclosporine regimen can be justified in severe
      psoriasis not responsive to other treatments. When cyclosporine administration is
      required, obesity, pre-treatment controlled hypertension, increased age (>70
      years), and metabolic syndrome should be taken into consideration, as a
      significant correlation with occurrence of cyclosporine-induced side effects has
      been found.

PMID- 23171022
TI  - Foreign body granuloma caused by hyaluronic acid/dextranomer microsphere filler
      injection.

PMID- 23171023
TI  - Mycobacterium smegmatis soft tissue infection.

PMID- 23171024
TI  - Angiosarcoma on the lower abdominal wall associated with chronic lymphedema in an
      obese woman.

PMID- 23171028
TI  - Detection of lipid-rich prostate circulating tumour cells with coherent anti
      Stokes Raman scattering microscopy.
AB  - BACKGROUND: Circulating tumour cells (CTC) are an important indicator of
      metastasis and associated with a poor prognosis. Detection sensitivity and
      specificity of CTC in the peripheral blood of metastatic cancer patient remain a
      technical challenge. METHODS: Coherent anti-Stokes Raman scattering (CARS)
      microscopy was employed to examine the lipid content of CTC isolated from the
      peripheral blood of metastatic prostate cancer patients. CARS microscopy was also
      employed to evaluate lipid uptake and mobilization kinetics of a metastatic human
      prostate cancer cell line. RESULTS: One hundred CTC from eight metastatic
      prostate cancer patients exhibited strong CARS signal which arose from
      intracellular lipid. In contrast, leukocytes exhibited weak CARS signal which
      arose mostly from cellular membrane. On average, CARS signal intensity of
      prostate CTC was 7-fold higher than that of leukocytes (P<0.0000001). When
      incubated with human plasma, C4-2 metastatic human prostate cancer cells
      exhibited rapid lipid uptake kinetics and slow lipid mobilization kinetics.
      Higher expression of lipid transport proteins in C4-2 cells compared to non
      transformed RWPE-1 and non-malignant BPH-1 prostate epithelial cells further
      indicated strong affinity for lipid of metastatic prostate cancer cells.
      CONCLUSIONS: Intracellular lipid could serve as a biomarker for prostate CTC
      which could be sensitively detected with CARS microscopy in a label-free manner.
      Strong affinity for lipid by metastatic prostate cancer cells could be used to
      improve detection sensitivity and therapeutic targeting of prostate CTC.

PMID- 23171030
TI  - The copper supply pathway to a Salmonella Cu,Zn-superoxide dismutase (SodCII)
      involves P(1B)-type ATPase copper efflux and periplasmic CueP.
AB  - Periplasmic Cu,Zn-superoxide dismutases (Cu,Zn-SODs) are implicated in bacterial
      virulence. It has been proposed that some bacterial P(1B)-type ATPases supply
      copper to periplasmic cupro-proteins and such transporters have also been
      implicated in virulence. Here we show that either of two P(1B)-type ATPases, CopA
      or GolT, is needed to activate a periplasmic Cu,Zn-SOD (SodCII) in Salmonella
      enterica serovar Typhimurium. A DeltacopA/DeltagolT mutant accumulates inactive
      Zn-SodCII which can be activated by copper-supplementation in vitro. In contrast,
      either single ATPase mutant accumulates fully active Cu,Zn-SodCII. A contribution
      of GolT to copper handling is consistent with its copper-responsive transcription
      mediated by DNA-binding metal-responsive activator GolS. The requirement for
      duplicate transcriptional activators CueR and GolS remains unclear since both
      have similar tight K(Cu). Mutants lacking periplasmic cupro-protein CueP also
      accumulate inactive Zn-SodCII and while CopA and GolT show functional redundancy,
      both require CueP to activate SodCII in vivo. Zn-SodCII is also activated in
      vitro by incubation with Cu-CueP and this coincides with copper transfer as
      monitored by electron paramagnetic resonance spectroscopy. These experiments
      establish a role for CueP within the copper supply pathway for Salmonella Cu,Zn
      SodCII. Copper binding by CueP in this pathogen may confer protection of the
      periplasm from copper-mediated damage while sustaining vital cupro-enzyme
      activity.

PMID- 23171031
TI  - Wide bandwidth nanowire electromechanics on insulating substrates at room
      temperature.
AB  - We study InAs nanowire resonators fabricated on sapphire substrate with a local
      gate configuration. The key advantage of using an insulating sapphire substrate
      is that it results in a reduced parasitic capacitance, thus allowing both wide
      bandwidth actuation and detection using a network analyzer as well as signal
      detection at room temperature. Both in-plane and out-of-plane vibrational modes
      of the nanowire can be driven and the nonlinear response of the resonators
      studied. In addition, this technique enables the study of variation of thermal
      strains due to heating in nanostructures.

PMID- 23171029
TI  - Review: experimental manipulations of microglia in mouse models of Alzheimer's
      pathology: activation reduces amyloid but hastens tau pathology.
AB  - The inflammation hypothesis of Alzheimer's pathogenesis has directed much
      scientific effort towards ameliorating this disease. The development of mouse
      models of amyloid deposition permitted direct tests of the proposal that amyloid
      activated microglia could cause neurodegeneration in vivo. Many approaches to
      manipulating microglial activation have been applied to these mouse models, and
      are the subject of this review. In general, these results do not support a direct
      neuricidal action of microglia in mouse amyloid models under any activation
      state. Some of the manipulations cause both a reduction in pathology and a
      reduction in microglial activation. However, at least for agents like ibuprofen,
      this outcome may result from a direct action on amyloid production, and a
      reduction in the microglial-provoking amyloid deposits, rather than from reduced
      microglial activation leading to a decline in amyloid deposition. Instead, a
      surprising number of the experimental manipulations which increase microglial
      activation lead to enhanced clearance of the amyloid deposits. Both the
      literature and new data presented here suggest that either classical or
      alternative activation of microglia can lead to enhanced amyloid clearance.
      However, a limited number of studies comparing the same treatments in amyloid
      depositing vs. tau-depositing mice find the opposite effects. Treatments that
      benefit amyloid pathology accelerate tau pathology. This observation argues
      strongly that potential treatments be tested for impact on both amyloid and tau
      pathology before consideration of testing in humans.

PMID- 23171032
TI  - Yeast ratio is a critical factor for sequential fermentation of papaya wine by
      Williopsis saturnus and Saccharomyces cerevisiae.
AB  - The growth kinetics and fermentation performance of Williopsis saturnus and
      Saccharomyces cerevisiae at ratios of 10:1, 1:1 and 1:10 (W.:S.) were studied in
      papaya juice with initial 7-day fermentation by W.saturnus, followed by S.
      cerevisiae. The growth kinetics of W. saturnus were similar at all ratios, but
      its maximum cell count decreased as the proportion of S. cerevisiae was
      increased. Conversely, there was an early death of S. cerevisiae at the ratio of
      10:1. Williopsis saturnus was the dominant yeast at 10:1 ratio that produced
      papaya wine with elevated concentrations of acetate esters. On the other hand,
      1:1 and 1:10 ratios allowed the coexistence of both yeasts which enabled the
      flavour-enhancing potential of W.saturnus as well as the ethyl ester and alcohol
      producing abilities of S. cerevisiae. In particular, 1:1 and 1:10 ratios resulted
      in production of more ethyl esters, alcohols and 2-phenylethyl acetate. However,
      the persistence of both yeasts at 1:1 and 1:10 ratios led to formation of high
      levels of acetic acid. The findings suggest that yeast ratio is a critical factor
      for sequential fermentation of papaya wine by W.saturnus and S. cerevisiae as a
      strategy to modulate papaya wine flavour.

PMID- 23171033
TI  - Ca(2+) enhances Abeta polymerization rate and fibrillar stability in a dynamic
      manner.
AB  - Identifying factors that affect the self-assembly of Abeta (amyloid-beta peptide)
      is of utmost importance in the quest to understand the molecular mechanisms
      causing AD (Alzheimer's disease). Ca(2+) has previously been shown to accelerate
      both Abeta fibril nucleation and maturation, and dysregulated Ca(2+) homoeostasis
      frequently correlates with development of AD. The mechanisms regarding Ca(2+)
      binding, as well as its effect on fibril kinetics, are not fully understood.
      Using a polymerization assay we show that Ca(2+) in a dynamic and reversible
      manner enhances both the elongation rate and fibrillar stability, where
      specifically the 'dock and lock' phase mechanism is enhanced. Through NMR
      analysis we found that Ca(2+) affects the fibrillar architecture. In addition,
      and unexpectedly, we found that Ca(2+) does not bind the free Abeta monomer. This
      implies that Ca(2+) binding requires an architecture adopted by assembled
      peptides, and consequently is mediated through intermolecular interactions
      between adjacent peptides. This gives a mechanistic explanation to the enhancing
      effect on fibril maturation and indicates structural similarities between
      prefibrillar structures and mature amyloid. Taken together we show how Ca(2+)
      levels affect the delicate equilibrium between the monomeric and assembled Abeta
      and how fluctuations in vivo may contribute to development and progression of the
      disease.

PMID- 23171034
TI  - Life impact of ankle fractures: qualitative analysis of patient and clinician
      experiences.
AB  - BACKGROUND: Ankle fractures are one of the more commonly occurring forms of
      trauma managed by orthopaedic teams worldwide. The impacts of these injuries are
      not restricted to pain and disability caused at the time of the incident, but may
      also result in long term physical, psychological, and social consequences. There
      are currently no ankle fracture specific patient-reported outcome measures with a
      robust content foundation. This investigation aimed to develop a thematic
      conceptual framework of life impacts following ankle fracture from the
      experiences of people who have suffered ankle fractures as well as the health
      professionals who treat them. METHODS: A qualitative investigation was undertaken
      using in-depth semi-structured interviews with people (n=12) who had previously
      sustained an ankle fracture (patients) and health professionals (n=6) that treat
      people with ankle fractures. Interviews were audio-recorded and transcribed. Each
      phrase was individually coded and grouped in categories and aligned under
      emerging themes by two independent researchers. RESULTS: Saturation occurred
      after 10 in-depth patient interviews. Time since injury for patients ranged from
      6 weeks to more than 2 years. Experience of health professionals ranged from 1
      year to 16 years working with people with ankle fractures. Health professionals
      included an Orthopaedic surgeon (1), physiotherapists (3), a podiatrist (1) and
      an occupational therapist (1). The emerging framework derived from patient data
      included eight themes (Physical, Psychological, Daily Living, Social,
      Occupational and Domestic, Financial, Aesthetic and Medication Taking). Health
      professional responses did not reveal any additional themes, but tended to focus
      on physical and occupational themes. CONCLUSIONS: The nature of life impact
      following ankle fractures can extend beyond short term pain and discomfort into
      many areas of life. The findings from this research have provided an empirically
      derived framework from which a condition-specific patient-reported outcome
      measure can be developed.

PMID- 23171035
TI  - HIV/AIDS-related attitudes and practices among traditional healers in Zambezia
      Province, Mozambique.
AB  - OBJECTIVES: To document HIV knowledge, treatment practices, and the willingness
      of traditional healers to engage with the health system in Zambezia Province,
      Mozambique. SETTINGS/LOCATION: Traditional healers offer culturally acceptable
      services and are more numerous in Mozambique than are allopathic providers. Late
      presentation of human immunodeficiency virus (HIV) infection/acquired
      immunodeficiency syndrome (AIDS) is reported among persons who have first sought
      care from traditional healers. DESIGN: One hundred and thirty-nine (139)
      traditional healers were interviewed in their native languages (Chuabo or Lomwe)
      in Zambezia Province. Furthermore, 24 traditional healers were observed during
      patient encounters. Healers answered a semistructured questionnaire regarding
      their knowledge of HIV/AIDS, general treatment practices, attitudes toward the
      allopathic health system, and their beliefs in their abilities to cure AIDS.
      RESULTS: Traditional healers were older and had less formal education than the
      general population. Razor cutting in order to rub herbs into blooded skin was
      observed, and healers reported razor cutting as a routine practice. Healers
      stated that they did not refer HIV patients to clinics for two principal reasons:
      (1) patient symptoms/signs of HIV were unrecognized, and (2) practitioners
      believed they could treat the illness effectively themselves. Traditional healers
      were far more likely to believe in a spiritual than an infectious origin of HIV
      disease. Prior HIV/AIDS training was not associated with better knowledge or
      referral practices, though 81% of healers were interested in engaging allopathic
      providers. CONCLUSIONS: It was found that the HIV-related practices of
      traditional healers probably increase risk for both HIV-infected and uninfected
      persons through delayed care and reuse of razors. Mozambican traditional healers
      attribute HIV pathogenesis to spiritual, not infectious, etiologies. Healers who
      had received prior HIV training were no more knowledgeable, nor did they have
      better practices. The willingness expressed by 4 in 5 healers to engage local
      formal health providers in HIV/AIDS care suggests a productive way forward,
      though educational efforts must be effective and income concerns considered.

PMID- 23171036
TI  - Metformin: a cheap and well-tolerated drug that provides benefits for viral
      infections.
AB  - OBJECTIVES: Insulin resistance in viral infections is common. We have explored
      the effectiveness of metformin for alleviating insulin resistance in HIV-infected
      patients and assessed the relevance of the ataxia-telangiectasia mutated (ATM)
      rs11212617 variant in the clinical response with the rationale that metformin
      modulates cellular bioenergetics in an ATM-dependent process. METHODS: HIV
      infected patients (n = 385) were compared with controls recruited from the
      general population (n = 300) with respect to the genotype distribution of the ATM
      rs11212617 variant and its influence on selected metabolic and inflammatory
      variables. We also followed up a subset of male patients with HIV and hepatitis C
      virus (HCV) coinfection (n = 47) who were not receiving antiviral treatment and
      for whom metformin was prescribed for insulin resistance, which tends to have a
      higher incidence and severity in coinfected patients. RESULTS: Among the HIV
      infected patients, human cytomegalovirus (91.9%) and HCV (62.3%) coinfections
      were frequent. Selected metabolic and/or inflammatory variables were
      significantly altered in infected patients. Treatment with metformin in HIV and
      HCV coinfected patients was well tolerated and significantly increased the
      sensitivity of peripheral tissues to insulin. The minor allele (C) of the
      rs11212617 variant was associated with treatment success and may affect the
      course of insulin resistance in response to metformin (odds ratio 1.21; 95%
      confidence interval 1.07-1.39; P = 0.005). There were no differences between
      treated and untreated patients in viral loads or variables measuring immune
      defence, indicating that toxicity is unlikely. CONCLUSIONS: We provide novel data
      suggesting that identification of the ATM rs11212617 variant may be important in
      assessing the glycaemic response to metformin treatment for insulin resistance in
      HIV-infected patients.

PMID- 23171037
TI  - Gender differences in pain severity, disability, depression, and widespread
      pressure pain sensitivity in patients with fibromyalgia syndrome without comorbid
      conditions.
AB  - OBJECTIVES: To determine the differences in pain, disability, depression, and
      pressure sensitivity between men and women with fibromyalgia syndrome (FMS), and
      to analyze the relationship between pain and pressure sensitivity in FMS. DESIGN:
      A cross-sectional study. SETTING: Gender differences in pain sensitivity in
      individuals with FMS have not been yet clarified. PATIENTS: Twenty-four men (age:
      52 +/- 6 years) and 24 age-matched women (age: 52 +/- 5 years) with FMS diagnosed
      according to 1990 American College of Rheumatology criteria participated. OUTCOME
      MEASURES: Pressure pain thresholds (PPTs) over the 18 tender points and over the
      second metacarpal and tibialis anterior muscle were assessed. The intensity and
      duration of pain, tender point count, the Fibromyalgia Impact Questionnaire, and
      depression (Beck Depression Inventory-II) were calculated. RESULTS: Women
      reported higher intensity of pain, tender point count, and depression than men (P
      < 0.01). Men reported a longer history of pain and disability than women (P =
      0.005). Women showed bilateral lower PPT over suboccipital, cervical spine,
      second rib, supraspinatus, lateral epicondyle, gluteal region, and second
      metacarpal than men (P < 0.05). Negative associations between tender point count
      and PPT were found in men and women. In men, negative correlations between the
      intensity of ongoing pain and PPT over the cervical spine were found. No
      significant association between PPT and other clinical outcome was seen.
      CONCLUSIONS: Women with FMS showed higher pain severity and lower PPT than men,
      whereas men exhibited longer duration of symptoms and disability. In men with
      FMS, the intensity of ongoing pain was positively correlated to pressure
      hyperalgesia over the neck. This study suggests that FMS could show a different
      phenotype in women and men and confirm that women exhibit lower PPT than men.

PMID- 23171038
TI  - The effect of implant design of linked total elbow arthroplasty on stability and
      stress: a finite element analysis.
AB  - Several linked total elbow arthroplasty designs exist, which function similar to
      a loose hinge joint. Constraint behaviour is an important design consideration,
      as it affects joint stability, or how much secondary [e.g. varus-valgus (VV)]
      motion is permitted. Implant durability is also a concern, as bearing failures
      have been reported. This finite element analysis investigates the constraint
      characteristics and ultra high molecular weight polyethylene bearing stresses of
      three linked elbow design concepts [cylindrical (CY), hourglass (HG) and concave
      cylinder (CC)]. The bearing of the CY design was subjected to elevated Von Mises
      stresses (2.1-5.4 times higher than the HG and CC designs) due to edge loading.
      The HG design maintained low stresses, but was unable to provide consistent VV
      stability. The CC design also maintained low stresses while providing consistent
      VV stability. These results suggest that CC designs may provide better stability
      characteristics and durability in vivo, compared to the other two designs.

PMID- 23171039
TI  - Metabolism of 4-chloro-2-nitrophenol in a gram-positive bacterium,
      Exiguobacterium sp. PMA.
AB  - BACKGROUND: Chloronitrophenols (CNPs) are widely used in the synthesis of dyes,
      drugs and pesticides, and constitute a major group of environmental pollutants. 4
      Chloro-2-nitrophenol (4C2NP) is an isomer of CNPs that has been detected in
      various industrial effluents. A number of physicochemical methods have been used
      for treatment of wastewater containing 4C2NP. These methods are not as effective
      as microbial degradation, however. RESULTS: A 4C2NP-degrading bacterium,
      Exiguobacterium sp. PMA, which uses 4C2NP as the sole carbon and energy source
      was isolated from a chemically-contaminated site in India. Exiguobacterium sp.
      PMA degraded 4C2NP with the release of stoichiometeric amounts of chloride and
      ammonium ions. The effects of different substrate concentrations and various
      inoculum sizes on degradation of 4C2NP were investigated. Exiguobacterium sp. PMA
      degraded 4C2NP up to a concentration of 0.6 mM. High performance liquid
      chromatography and gas chromatography-mass spectrometry identified 4-chloro-2
      aminophenol (4C2AP) and 2-aminophenol (2AP) as possible metabolites of the 4C2NP
      degradation pathway. The crude extract of 4C2NP-induced PMA cells contained
      enzymatic activity for 4C2NP reductase and 4C2AP dehalogenase, suggesting the
      involvement of these enzymes in the degradation of 4C2NP. Microcosm studies using
      sterile and non-sterile soils spiked with 4C2NP were carried out to monitor the
      bioremediation potential of Exiguobacterium sp. PMA. The bioremediation of 4C2NP
      by Exiguobacterium sp. PMA was faster in non-sterilized soil than sterilized
      soil. CONCLUSIONS: Our studies indicate that Exiguobacterium sp. PMA may be
      useful for the bioremediation of 4C2NP-contaminated sites. This is the first
      report of (i) the formation of 2AP in the 4C2NP degradation pathway by any
      bacterium and (iii) the bioremediation of 4C2NP by any bacterium.

PMID- 23171040
TI  - Reduced Plasmodium berghei sporozoite liver load associates with low protective
      efficacy after intradermal immunization.
AB  - Studies in animal models suggest that protection against malaria induced by
      intradermal (ID) administration of sporozoites is less effective compared to
      intravenous injection (IV). We investigated in a murine model the protective
      efficacy and immune responses after ID or IV immunization of sporozoites. Mice
      were immunized via either IV or ID route with Plasmodium berghei sporozoites in
      combination with chloroquine treatment (CPS) (allowing full liver stage
      development) or by gamma-radiation-attenuated sporozoites (RAS) (early liver
      stage arrest). While IV immunization with both RAS and CPS generated 90-100%
      protection, ID immunization resulted in reduced levels of protection with either
      immunization strategy in both Balb/cByJ (50%) and C57BL/6j mice (7-13%). Lower
      protection by ID routing associated with a 30-fold lower parasite liver load [P <
      0.001 (chi(2) = 49.08, d.f. = 1)] assessed by real-time in vivo imaging of
      bioluminescent P. berghei parasites. Unlike IV, ID immunization did not result in
      expansion of CD8+ T cells with effector memory phenotype and showed lower
      IFNgamma responses irrespective of the immunization regime. In conclusion,
      protection against sporozoite infection is likely dependent on parasite liver
      infection and subsequently generated cellular immune responses.

PMID- 23171043
TI  - Prope tolerance after pediatric liver transplantation.
AB  - pT, under mono- and infratherapeutic calcineurin inhibition, may constitute an
      optimal condition combining graft acceptance with low IS load and minimal IS
      related toxicity. We reviewed 171 pediatric (<15.0 yr) survivors beyond one yr
      after LT, transplanted between April 1999 and June 2007 under tacrolimus-based
      regimens (median follow-up post-LT: 6.0 yr, range: 0.8-9.5 yr). Their current
      status regarding IS therapy was analyzed and correlated with initial
      immunoprophylaxis. pT was defined as tacrolimus monotherapy, with mean trough
      blood levels <4 ng/mL during the preceding year of follow-up, combined with
      normal liver function tests. The 66 children transplanted before April 2001
      received a standard tacrolimus-steroid regimen. Beyond April 2001, 105 patients
      received steroid-free tacrolimus-basiliximab or tacrolimus-daclizumab
      immunoprophylaxis. In the latter group, 43 (41%) never experienced any acute
      rejection episode and never received steroids. In the long term, a total of 79
      recipients (47%) developed pT (n = 73) or IS-free operational tolerance (n = 6),
      27 of them belonging to the 43 steroid-free patients (63%). In contrast, only
      52/128 (41%) children treated with steroids subsequently developed
      prope/operational tolerance (p = 0.012). Steroid-free tacrolimus-based IS seems
      to promote long-term graft acceptance under minimal/no IS. These results
      constitute the first evidence that minimization of IS, including steroid
      avoidance, might be tolerogenic in the long term after pediatric LT.

PMID- 23171044
TI  - Range-wide population genetic structure of the Caribbean sea fan coral, Gorgonia
      ventalina.
AB  - The population structure of benthic marine organisms is of central relevance to
      the conservation and management of these often threatened species, as well as to
      the accurate understanding of their ecological and evolutionary dynamics. A
      growing body of evidence suggests that marine populations can be structured over
      short distances despite theoretically high dispersal potential. Yet the proposed
      mechanisms governing this structure vary, and existing empirical population
      genetic evidence is of insufficient taxonomic and geographic scope to allow for
      strong general inferences. Here, we describe the range-wide population genetic
      structure of an ecologically important Caribbean octocoral, Gorgonia ventalina.
      Genetic differentiation was positively correlated with geographic distance and
      negatively correlated with oceanographically modelled dispersal probability
      throughout the range. Although we observed admixture across hundreds of
      kilometres, estimated dispersal was low, and populations were differentiated
      across distances <2 km. These results suggest that populations of G. ventalina
      may be evolutionarily coupled via gene flow but are largely demographically
      independent. Observed patterns of differentiation corroborate biogeographic
      breaks found in other taxa (e.g. an east/west divide near Puerto Rico), and also
      identify population divides not discussed in previous studies (e.g. the Yucatan
      Channel). High genotypic diversity and absence of clonemates indicate that sex is
      the primary reproductive mode for G. ventalina. A comparative analysis of the
      population structure of G. ventalina and its dinoflagellate symbiont,
      Symbiodinium, indicates that the dispersal of these symbiotic partners is not
      coupled, and symbiont transmission occurs horizontally.

PMID- 23171045
TI  - New 2-(aryloxy)-3-phenylpropanoic acids as peroxisome proliferator-activated
      receptor alpha/gamma dual agonists able to upregulate mitochondrial carnitine
      shuttle system gene expression.
AB  - The preparation of a series of 2-(aryloxy)-3-phenylpropanoic acids, resulting
      from the introduction of different substituents into the biphenyl system of the
      previously reported peroxisome proliferator-activated receptor alpha/gamma
      (PPARalpha/gamma) dual agonist 1, allowed the identification of new ligands with
      higher potency on PPARalpha and fine-tuned moderate PPARgamma activity. For the
      most promising stereoisomer (S)-16, X-ray and calorimetric studies in PPARgamma
      revealed, at high ligand concentration, the presence of two molecules
      simultaneously bound to the receptor. On the basis of these results and docking
      experiments in both receptor subtypes, a molecular explanation was provided for
      its different behavior as a full and partial agonist of PPARalpha and PPARgamma,
      respectively. The effects of (S)-16 on mitochondrial acylcarnitine carrier and
      carnitine-palmitoyl-transferase 1 gene expression, two key components of the
      carnitine shuttle system, were also investigated, allowing the hypothesis of a
      more beneficial pharmacological profile of this compound compared to the less
      potent PPARalpha agonist fibrates currently used in therapy.

PMID- 23171046
TI  - Psoriasis and sexual behavior in U.S. women: an epidemiologic analysis using the
      National Health and Nutrition Examination Survey (NHANES).
AB  - INTRODUCTION: Although sexual behavior is an integral part of most adults'
      overall well-being, this aspect of psoriasis patients' quality of life is rarely
      explored. AIM: The aim of this study is to assess the relationship between
      psoriasis and sexual behavior in U.S. women. METHODS: We analyzed data from the
      National Health and Nutrition Examination Survey (NHANES) from 2003 to 2006. Our
      study focuses on responses to the dermatology and sexual behavior questionnaires
      of the NHANES. MAIN OUTCOME MEASURES: This study examines the association between
      psoriasis and sexual behavior in U.S. women with regard to sexual orientation,
      age of first sexual encounter, number of sexual partners, and frequency of
      unprotected sex. RESULTS: A total of 3,462 women provided responses to their
      psoriasis status: 2,753 (80%) women were heterosexual and 709 (20%) were
      nonheterosexual. Among them, 2.7% reported a physician-given diagnosis of
      psoriasis. On multivariate analyses, psoriasis was not associated with
      differences in sexual orientation (odds ratio [OR] 0.90, 95% confidence interval
      [CI] 0.62-2.01). Among nonheterosexual women, multivariate analysis revealed a
      lower number of lifetime female sexual partners in women with psoriasis (rate
      ratio [RR] 0.11, 95% CI 0.04-0.33, P = 0.001). Among heterosexual women, no
      significant differences existed between those with and without psoriasis in age
      of first sexual encounter (weighted difference -0.54 years, 95% CI -1.27 to
      0.19), number of lifetime male sexual partners (RR 1.19, 95% CI 0.69-2.06), or
      number of lifetime male oral sex partners (RR 0.72, 95% CI 0.40-1.29).
      Heterosexual women with psoriasis had 1.13 times more unprotected sex (RR 1.13,
      95% CI 1.02-1.24, P = 0.03) compared with those without psoriasis. CONCLUSION:
      Psoriasis is associated with a significantly reduced number of sexual partners in
      nonheterosexual women. Psoriasis may differentially impact sexual behavior based
      on sexual orientation in women.

PMID- 23171047
TI  - Laparoscopic or Lichtenstein repair for recurrent inguinal hernia: a meta
      analysis of randomized controlled trials.
AB  - BACKGROUND: There is no clear answer regarding the use of laparoscopic techniques
      versus the Lichtenstein method for the treatment of recurrent inguinal hernia.
      OBJECTIVE: The aim of this study was to compare the outcomes of laparoscopy
      versus the Lichtenstein repair by a meta-analysis of available randomized
      controlled trials (RCTs). METHODS: Databases, including PubMed, EMBASE, the
      Cochrane Library, and the Science Citation Index updated to May 2012, were
      searched. The main outcome measures were wound infections and haematoma, urinary
      retention, post-operative chronic pain and recurrence. A meta-analysis of
      included RCTs was performed. RESULTS: Five RCTs, comprising a total of 427
      patients, were included. Although most of the analysed outcomes were similar
      between groups, wound infection rates and post-operative chronic pain occurred
      less frequently in the laparoscopic group than in the Lichtenstein group (odds
      ratio: 0.28, 95% CI: 0.08-0.97; P = 0.05; odds ratio: 0.33, 95% CI: 0.17-0.68; P
      = 0.002, respectively). CONCLUSION: The laparoscopic approach to the treatment of
      recurrent inguinal hernia is superior to the Lichtenstein hernioplasty in some
      aspects that affect patient satisfaction.

PMID- 23171049
TI  - Ordered phosphorylation events in two independent cascades of the PTEN C-tail
      revealed by NMR.
AB  - PTEN phosphatase is a tumor suppressor controlling notably cell growth,
      proliferation and survival. The multisite phosphorylation of the PTEN C-terminal
      tail regulates PTEN activity and intracellular trafficking. The dynamical nature
      of such regulatory events represents a crucial dimension for timing cellular
      decisions. Here we show that NMR spectroscopy allows reporting on the order and
      kinetics of clustered multisite phosphorylation events. We first unambiguously
      identify in vitro seven bona fide sites modified by CK2 and GSK3beta kinases and
      two new sites on the PTEN C-terminal tail. Then, monitoring the formation of
      transient intermediate phosphorylated states, we determine the sequence of these
      reactions and calculate their apparent rate constants. Finally, we assess the
      dynamic formation of these phosphorylation events induced by endogenous kinases
      directly in extracts of human neuroblastoma cells. Taken together, our data
      indicate that two cascades of events controlled by CK2 and GSK3beta occur
      independently on two clusters of sites (S380-S385 and S361-S370) and that in each
      cluster the reactions follow an ordered model with a distributive kinetic
      mechanism. Besides emphasizing the ability of NMR to quantitatively and
      dynamically follow post-translational modifications, these results bring a
      temporal dimension on the establishment of PTEN phosphorylation cascades.

PMID- 23171048
TI  - SNF8, a member of the ESCRT-II complex, interacts with TRPC6 and enhances its
      channel activity.
AB  - BACKGROUND: Transient receptor potential canonical (TRPC) channels are non
      selective cation channels involved in receptor-mediated calcium signaling in
      diverse cells and tissues. The canonical transient receptor potential 6 (TRPC6)
      has been implicated in several pathological processes, including focal segmental
      glomerulosclerosis (FSGS), cardiac hypertrophy, and pulmonary hypertension. The
      two large cytoplasmic segments of the cation channel play a critical role in the
      proper regulation of channel activity, and are involved in several protein
      protein interactions. RESULTS: Here we report that SNF8, a component of the
      endosomal sorting complex for transport-II (ESCRT-II) complex, interacts with
      TRPC6. The interaction was initially observed in a yeast two-hybrid screen using
      the amino-terminal cytoplasmic domain of TRPC6 as bait, and confirmed by co
      immunoprecipitation from eukaryotic cell extracts. The amino-terminal 107 amino
      acids are necessary and sufficient for the interaction. Overexpression of SNF8
      enhances both wild-type and gain-of-function mutant TRPC6-mediated whole-cell
      currents in HEK293T cells. Furthermore, activation of NFAT-mediated transcription
      by gain-of-function mutants is enhanced by overexpression of SNF8, and partially
      inhibited by RNAi mediated knockdown of SNF8. Although the ESCRT-II complex
      functions in the endocytosis and lysosomal degradation of transmembrane proteins,
      SNF8 overexpression does not alter the amount of TRPC6 present on the cell
      surface. CONCLUSION: SNF8 is novel binding partner of TRPC6, binding to the amino
      terminal cytoplasmic domain of the channel. Modulating SNF8 expression levels
      alters the TRPC6 channel current and can modulate activation of NFAT-mediated
      transcription downstream of gain-of-function mutant TRPC6. Taken together, these
      results identify SNF8 as a novel regulator of TRPC6.

PMID- 23171050
TI  - Early risky drug use detection in primary healthcare: how does it work in the
      real world?
AB  - Despite effectiveness in research, the efficacy of screening and brief
      intervention (SBI) for risky substance users is not adequately understood in
      routine clinical practice. Primary healthcare professionals (n = 103) from three
      cities in a metropolitan area in Brazil were trained and supervised in SBI and
      then screened 40 patients. One year later, meetings were held in each city to
      obtain feedback. Twenty professionals who fulfilled the task (Yes [Y]) and 24 who
      did not (No [N]) were individually interviewed about their SBI experience.
      Reports were independently interpreted and codified by two researchers. The Y and
      N groups reported the same barriers and positive beliefs, but only the Y group
      reported no negative issues. The present study lasted from 2007 to 2009.

PMID- 23171052
TI  - Norepinephrine stimulates progesterone production in highly estrogenic bovine
      granulosa cells cultured under serum-free, chemically defined conditions.
AB  - BACKGROUND: Since noradrenergic innervation was described in the ovarian
      follicle, the actions of the intraovarian catecholaminergic system have been the
      focus of a variety of studies. We aimed to determine the gonadotropin-independent
      effects of the catecholamine norepinephrine (NE) in the steroid hormone profile
      of a serum-free granulosa cell (GC) culture system in the context of follicular
      development and dominance. METHODS: Primary bovine GCs were cultivated in a serum
      free, chemically defined culture system supplemented with 0.1% polyvinyl alcohol.
      The culture features were assessed by hormone measurements and ultrastructural
      characteristics of GCs. RESULTS: GCs produced increasing amounts of estradiol and
      pregnenolone for 144h and maintained ultrastructural features of healthy
      steroidogenic cells. Progesterone production was also detected, although it
      significantly increased only after 96h of culture. There was a highly significant
      positive correlation between estradiol and pregnenolone production in high E2
      producing cultures. The effects of NE were further evaluated in a dose-response
      study. The highest tested concentration of NE (10 (-7) M) resulted in a
      significant increase in progesterone production, but not in estradiol or
      pregnenolone production. The specificity of NE effects on progesterone production
      was further investigated by incubating GCs with propranolol (10 (-8) M), a non
      selective beta-adrenergic antagonist. CONCLUSIONS: The present culture system
      represents a robust model to study the impact of intrafollicular factors, such as
      catecholamines, in ovarian steroidogenesis and follicular development. The
      results of noradrenergic effects in the steroidogenesis of GC have implications
      on physiological follicular fate and on certain pathological ovarian conditions
      such as cyst formation and anovulation.

PMID- 23171053
TI  - Association between radiographic Wallerian degeneration and neuropathological
      changes post childhood stroke.
AB  - AIM: Wallerian degeneration is a radiological finding thought to reflect
      corticospinal tract degeneration. This finding on magnetic resonance imaging
      (MRI) is routinely used as a predictor of poor prognosis in childhood stroke.
      However, its validity has never been established. Our objective was to correlate
      Wallerian degeneration seen on MRI with histopathology. METHOD: We searched the
      databases of the Department of Pathology and Children's Stroke registry at the
      Hospital for Sick Children, Toronto for autopsy specimens exhibiting focal
      infarcts from children born at term who underwent MRI after a stroke. The
      specimens were examined for Wallerian degeneration and then correlated with the
      pre-mortem MRI findings. RESULTS: Seven children (four females, three males) with
      a median age of 11 years (1-17 y) at the time of stroke met the inclusion
      criteria for this study. Of the seven children included in the study with
      ischaemic or haemorrhagic infarcts, six had concordant Wallerian degeneration
      findings on both MRI and post-mortem histopathological examination. The median
      time between stroke and death was 20 days (3-1825 d). INTERPRETATION: Our results
      show for the first time that the radiographic finding of Wallerian degeneration
      is a valid biomarker of corticospinal tract degeneration in children who have had
      ischaemic or haemorrhagic stroke.

PMID- 23171051
TI  - Genomic insights into strategies used by Xanthomonas albilineans with its reduced
      artillery to spread within sugarcane xylem vessels.
AB  - BACKGROUND: Xanthomonas albilineans causes leaf scald, a lethal disease of
      sugarcane. X. albilineans exhibits distinctive pathogenic mechanisms, ecology and
      taxonomy compared to other species of Xanthomonas. For example, this species
      produces a potent DNA gyrase inhibitor called albicidin that is largely
      responsible for inducing disease symptoms; its habitat is limited to xylem; and
      the species exhibits large variability. A first manuscript on the complete genome
      sequence of the highly pathogenic X. albilineans strain GPE PC73 focused
      exclusively on distinctive genomic features shared with Xylella fastidiosa
      another xylem-limited Xanthomonadaceae. The present manuscript on the same genome
      sequence aims to describe all other pathogenicity-related genomic features of X.
      albilineans, and to compare, using suppression subtractive hybridization (SSH),
      genomic features of two strains differing in pathogenicity. RESULTS: Comparative
      genomic analyses showed that most of the known pathogenicity factors from other
      Xanthomonas species are conserved in X. albilineans, with the notable absence of
      two major determinants of the "artillery" of other plant pathogenic species of
      Xanthomonas: the xanthan gum biosynthesis gene cluster, and the type III
      secretion system Hrp (hypersensitive response and pathogenicity). Genomic
      features specific to X. albilineans that may contribute to specific adaptation of
      this pathogen to sugarcane xylem vessels were also revealed. SSH experiments led
      to the identification of 20 genes common to three highly pathogenic strains but
      missing in a less pathogenic strain. These 20 genes, which include four ABC
      transporter genes, a methyl-accepting chemotaxis protein gene and an
      oxidoreductase gene, could play a key role in pathogenicity. With the exception
      of hypothetical proteins revealed by our comparative genomic analyses and SSH
      experiments, no genes potentially involved in any offensive or counter-defensive
      mechanism specific to X. albilineans were identified, supposing that X.
      albilineans has a reduced artillery compared to other pathogenic Xanthomonas
      species. Particular attention has therefore been given to genomic features
      specific to X. albilineans making it more capable of evading sugarcane
      surveillance systems or resisting sugarcane defense systems. CONCLUSIONS: This
      study confirms that X. albilineans is a highly distinctive species within the
      genus Xanthomonas, and opens new perpectives towards a greater understanding of
      the pathogenicity of this destructive sugarcane pathogen.

PMID- 23171054
TI  - Legionnaires' disease from a cooling tower in a community outbreak in Lidkoping,
      Sweden- epidemiological, environmental and microbiological investigation
      supported by meteorological modelling.
AB  - BACKGROUND: An outbreak of Legionnaires' Disease took place in the Swedish town
      Lidkoping on Lake Vanern in August 2004 and the number of pneumonia cases at the
      local hospital increased markedly. As soon as the first patients were diagnosed,
      health care providers were informed and an outbreak investigation was launched.
      METHODS: Classical epidemiological investigation, diagnostic tests, environmental
      analyses, epidemiological typing and meteorological methods. RESULTS: Thirty-two
      cases were found. The median age was 62 years (range 36 - 88) and 22 (69%) were
      males. No common indoor exposure was found. Legionella pneumophila serogroup 1
      was found at two industries, each with two cooling towers. In one cooling tower
      exceptionally high concentrations, 1.2 * 109 cfu/L, were found. Smaller amounts
      were also found in the other tower of the first industry and in one tower of the
      second plant. Sero- and genotyping of isolated L. pneumophila serogroup 1 from
      three patients and epidemiologically suspected environmental strains supported
      the cooling tower with the high concentration as the source. In all, two L.
      pneumophila strains were isolated from three culture confirmed cases and both
      these strains were detected in the cooling tower, but one strain in another
      cooling tower as well. Meteorological modelling demonstrated probable spread from
      the most suspected cooling tower towards the town centre and the precise location
      of four cases that were stray visitors to Lidkoping. CONCLUSIONS: Classical
      epidemiological, environmental and microbiological investigation of an LD
      outbreak can be supported by meteorological modelling methods.The broad
      competence and cooperation capabilities in the investigation team from different
      authorities were of paramount importance in stopping this outbreak.

PMID- 23171056
TI  - Review: membrane-associated misfolded protein propagation in natural
      transmissible spongiform encephalopathies (TSEs), synthetic prion diseases and
      Alzheimer's disease.
AB  - Protein misfolding has long been recognized as a primary cause of systemic
      amyloidosis and, increasingly, template-mediated misfolding of native host
      proteins is now also considered to be central pathogenetic events in some
      neurodegenerative diseases. Alzheimer's disease, naturally occurring
      transmissible spongiform encephalopathies (TSEs) and experimental disorders
      caused by misfolded prion protein (PrP) generated in vitro all share an imbalance
      of protein synthesis, aggregation and clearance that leads to protein
      aggregation, prompting some to suggest that Alzheimer's disease is caused by a
      prion-like mechanism. In TSEs, the host-coded, glycosyl-phosphoinositol (GPI)
      membrane-anchored prion protein (PrP(c) ) is misfolded into disease-associated,
      putatively infectious aggregates known as prions. In Alzheimer's disease the
      membrane-spanning Alzheimer's precursor protein (APP) is progressively cleaved
      within the plasmalemma to form Abeta peptide fragments that can form pathogenic
      extracellular aggregates while microtubule-associated tau proteins may also
      aggregate within neurones. Oligomeric Abeta peptides and full-length misfolded
      PrP show a common potential to convert native protein and aggregate on plasma
      membranes before subsequent release to form amyloid fibrils in the extracellular
      space. However, the nature, membrane topography and processing of the precursor
      and propagated proteins in prion and Alzheimer's disease all differ, and each
      group of diseases has distinctive spectra of additional pathological changes and
      clinical signs suggesting that fundamentally different disease mechanisms are
      involved.

PMID- 23171055
TI  - The downregulation of Mcl-1 via USP9X inhibition sensitizes solid tumors to Bcl
      xl inhibition.
AB  - BACKGROUND: It has been shown in many solid tumors that the overexpression of the
      pro-survival Bcl-2 family members Bcl-xL and Mcl-1 confers resistance to a
      variety of chemotherapeutic agents. Mcl-1 is a critical survival protein in a
      variety of cell lineages and is critically regulated via ubiquitination. METHODS:
      The Mcl-1, Bcl-xL and USP9X expression patterns in human lung and colon
      adenocarcinomas were evaluated via immunohistochemistry. Interaction between
      USP9X and Mcl-1 was demonstrated by immunoprecipitation-western blotting. The
      protein expression profiles of Mcl-1, Bcl-xL and USP9X in multiple cancer cell
      lines were determined by western blotting. Annexin-V staining and cleaved PARP
      western blotting were used to assay for apoptosis. The cellular toxicities after
      various treatments were measured via the XTT assay. RESULTS: In our current
      analysis of colon and lung cancer samples, we demonstrate that Mcl-1 and Bcl-xL
      are overexpressed and also co-exist in many tumors and that the expression levels
      of both genes correlate with the clinical staging. The downregulation of Mcl-1 or
      Bcl-xL via RNAi was found to increase the sensitivity of the tumor cells to
      chemotherapy. Furthermore, our analyses revealed that USP9X expression correlates
      with that of Mcl-1 in human cancer tissue samples. We additionally found that the
      USP9X inhibitor WP1130 promotes Mcl-1 degradation and increases tumor cell
      sensitivity to chemotherapies. Moreover, the combination of WP1130 and ABT-737, a
      well-documented Bcl-xL inhibitor, demonstrated a chemotherapeutic synergy and
      promoted apoptosis in different tumor cells. CONCLUSION: Mcl-1, Bcl-xL and USP9X
      overexpression are tumor survival mechanisms protective against chemotherapy.
      USP9X inhibition increases tumor cell sensitivity to various chemotherapeutic
      agents including Bcl-2/Bcl-xL inhibitors.

PMID- 23171057
TI  - A systematic review of the etiopathogenesis of Kienbock's disease and a critical
      appraisal of its recognition as an occupational disease related to hand-arm
      vibration.
AB  - BACKGROUND: We systematically reviewed etiological factors of Kienbock's disease
      (osteonecrosis of the lunate) discussed in the literature in order to examine the
      justification for including Kienbock's disease (KD) in the European Listing of
      Occupational Diseases. METHODS: We searched the Ovid/Medline and the Cochrane
      Library for articles discussing the etiology of osteonecrosis of the lunate
      published since the first description of KD in 1910 and up until July 2012 in
      English, French or German. Literature was classified by the level of evidence
      presented, the etiopathological hypothesis discussed, and the author's conclusion
      about the role of the etiopathological hypothesis. The causal relationship
      between KD and hand-arm vibration was elucidated by the Bradford Hill criteria.
      RESULTS: A total of 220 references was found. Of the included 152 articles, 140
      (92%) reached the evidence level IV (case series). The four most frequently
      discussed factors were negative ulnar variance (n=72; 47%), primary arterial
      ischemia of the lunate (n=63; 41%), trauma (n=63; 41%) and hand-arm vibration
      (n=53; 35%). The quality of the cohort studies on hand-arm vibration did not
      permit a meta-analysis to evaluate the strength of an association to KD. Evidence
      for the lack of consistency, plausibility and coherence of the 4 most frequently
      discussed etiopathologies was found. No evidence was found to support any of the
      nine Bradford Hill criteria for a causal relationship between KD and hand-arm
      vibration. CONCLUSIONS: A systematic review of 220 articles on the etiopathology
      of KD and the application of the Bradford Hill criteria does not provide
      sufficient scientific evidence to confirm or refute a causal relationship between
      KD and hand-arm vibration. This currently suggests that, KD does not comply with
      the criteria of the International Labour Organization determining occupational
      diseases. However, research with a higher level of evidence is required to
      further determine if hand-arm vibration is a risk factor for KD.

PMID- 23171058
TI  - High mobility field effect transistors based on macroscopically oriented
      regioregular copolymers.
AB  - Field-effect transistors fabricated from semiconducting conjugated polymers are
      candidates for flexible and low-cost electronic applications. Here, we
      demonstrate that the mobility of high molecular weight (300 kDa) regioregular,
      poly[4-(4,4-dihexadecyl-4H-cyclopenta[1,2-b:5,4-b']dithiophen-2-yl)-alt
      [1,2,5]thiadiazolo[3,4-c]pyridine] can be significantly improved by introducing
      long-range orientation of the polymer chains. By annealing for short periods,
      hole mobilities of 6.7 cm(2)/(V s) have been demonstrated. The transport is
      anisotropic, with a higher mobility (approximately 6:1) parallel to the polymer
      backbone than that perpendicular to the polymer backbone.

PMID- 23171060
TI  - Finite element modelling of human auditory periphery including a feed-forward
      amplification of the cochlea.
AB  - A three-dimensional finite element model is developed for the simulation of the
      sound transmission through the human auditory periphery consisting of the
      external ear canal, middle ear and cochlea. The cochlea is modelled as a straight
      duct divided into two fluid-filled scalae by the basilar membrane (BM) having an
      orthotropic material property with dimensional variation along its length. In
      particular, an active feed-forward mechanism is added into the passive cochlear
      model to represent the activity of the outer hair cells (OHCs). An iterative
      procedure is proposed for calculating the nonlinear response resulting from the
      active cochlea in the frequency domain. Results on the middle-ear transfer
      function, BM steady-state frequency response and intracochlear pressure are
      derived. A good match of the model predictions with experimental data from the
      literatures demonstrates the validity of the ear model for simulating sound
      pressure gain of middle ear, frequency to place map, cochlear sensitivity and
      compressive output for large intensity input. The current model featuring an
      active cochlea is able to correlate directly the sound stimulus in the ear canal
      with the vibration of BM and provides a tool to explore the mechanisms by which
      sound pressure in the ear canal is converted to a stimulus for the OHCs. 

PMID- 23171061
TI  - Export of the pneumococcal phage SV1 lysin requires choline-containing teichoic
      acids and is holin-independent.
AB  - Streptococcus pneumoniae bacteriophages (phages) rely on a holin-lysin system to
      accomplish host lysis. Due to the lack of lysin export signals, it is assumed
      that holin disruption of the cytoplasmic membrane allows endolysin access to the
      peptidoglycan. We investigated the lysis mechanism of pneumococcal phage SV1, by
      using lysogens without holin activity. Upon phage induction in a holin deficient
      background, phage lysin was gradually targeted to the cell wall, in spite of
      lacking any obvious signal sequence. Our data indicate that export of the phage
      lysin requires the presence of choline in the teichoic acids, an unusual
      characteristic of pneumococci. At the bacterial surface, the exolysin remains
      bound to choline residues without inducing lysis, but is readily activated by the
      collapse of the membrane potential. Additionally, the activation of the major
      autolysin LytA, which also participates in phage-mediated lysis, is equally
      related to perturbations of the membrane proton motive force. These results
      indicate that collapse of the membrane potential by holins is sufficient to
      trigger bacterial lysis. We found that the lysin of phage SV1 reaches the
      peptidoglycan through a novel holin-independent pathway and propose that the same
      mechanism could be used by other pneumococcal phages.

PMID- 23171062
TI  - The future of Obamacare.

PMID- 23171063
TI  - Lessons from Sandy--preparing health systems for future disasters.

PMID- 23171064
TI  - Sacroiliac steroid injections do not predict ablation relief-not a surprise.

PMID- 23171059
TI  - Inequalities in HIV disease management and progression in migrants from Latin
      America and sub-Saharan Africa living in Spain.
AB  - OBJECTIVES: The objective of the study was to analyse key HIV-related outcomes in
      migrants originating from Latin America and the Spanish-speaking Caribbean (LAC)
      or sub-Saharan Africa (SSA) living in Spain compared with native Spaniards (NSP).
      METHODS: The Cohort of the Spanish AIDS Research Network (CoRIS) is an open,
      prospective, multicentre cohort of antiretroviral-naive patients representing 13
      of the 17 Spanish regions. The study period was 2004-2010. Multivariate logistic
      or Fine and Gray regression models were fitted as appropriate to estimate the
      adjusted effect of region of origin on the different outcomes. RESULTS: Of the
      6811 subjects in CoRIS, 6278 were NSP (74.2%), LAC (19.4%) or SSA (6.4%). For
      these patients, the follow-up time was 15870 person-years. Compared with NSP, SSA
      and LAC under 35 years of age had a higher risk of delayed diagnosis [odds ratio
      (OR) 2.0 (95% confidence interval (CI) 1.5-2.8) and OR 1.7 (95% CI 1.4-2.1),
      respectively], as did LAC aged 35-50 years [OR 1.3 (95% CI 1.0-1.6)]. There were
      no major differences in time to antiretroviral therapy (ART) requirement or
      initiation. SSA exhibited a poorer immunological and virological response [hazard
      ratio (HR) [corrected] 0.8 (95% CI 0.7-1.0) and HR [corrected] 0.7 (95% CI 0.6
      0.9), respectively], while no difference was found for LAC. SSA and LAC showed an
      increased risk of AIDS for ages between 35 and 50 years [HR 2.0 (95% CI 1.1-3.7)
      and HR [corrected] 1.6 (95% CI 1.1-2.4), respectively], which was attributable to
      a higher incidence of tuberculosis. However, no statistically significant
      differences were observed in mortality. CONCLUSIONS: Migrants experience a
      disproportionate diagnostic delay, but no meaningful inequalities were identified
      regarding initiation of treatment after diagnosis. A poorer virological and
      immunological response was observed in SSA. Migrants had an increased risk of
      AIDS, which was mainly attributable to tuberculosis.

PMID- 23171065
TI  - Comparison of peritoneal fluid values after laparoscopic cryptorchidectomy using
      a vessel-sealing device (LigasureTM) versus a ligating loop and removal of the
      descended testis.
AB  - OBJECTIVE: To determine the effect of unilateral laparoscopic cryptorchidectomy
      and removal of the descended testis on peritoneal fluid values, and to compare
      effect between 2 methods for cryptorchid testis vessel hemostasis. STUDY DESIGN:
      Randomized clinical study. ANIMALS: Stallions (n = 10) with unilateral abdominal
      cryptorchid testis. METHODS: During standing laparoscopic cryptorchidectomy,
      blood vessels within the mesorchium of the cryptorchid testis were either sealed
      and transected with the LigaSure AtlasTM or 2 ligating loops were placed proximal
      to the testis and the tissue transected with laparoscopic scissors. The testis
      was removed through the body wall. After laparoscopic cryptorchidectomy,
      stallions were anesthetized and the descended testis was removed using a closed
      technique leaving the scrotal incision open. Abdominocenteses were performed
      before surgery, and 24, and 72 hours after surgery. RESULTS: Values for
      peritoneal total nucleated cell count (TNCC), total protein concentration (TP),
      and red blood cell count (RBCC) were all elevated at 24 and 72 hours when
      compared with baseline. Median TNCC for LigaSureTM (59,780 cells/MUL) was nearly
      twice that of the ligating loop (32,880 cells/MUL) at 24 hours postoperatively.
      There was no statistically significant difference in TNCC, TP, or RBCC between
      groups. CONCLUSIONS: TNCC, TP, and RBCC increase appreciably from baseline 24
      hours after laparoscopic cryptorchidectomy and closed castration but are markedly
      reduced by 72 hours.

PMID- 23171066
TI  - Unusual presentations of BK virus infections in pediatric renal transplant
      recipients.
AB  - BKV has emerged as a significant pathogen in the field of transplantation,
      predominantly causing BKV nephropathy in renal transplant recipients and
      hemorrhagic cystitis in HSCT recipients. However, case reports describe more
      diverse complications, and we too present three unusual cases of BKV infections
      in pediatric renal transplant recipients. First, we describe a case of biopsy
      proven renal damage secondary to BKV prior to the onset of viremia, demonstrating
      that BKV nephropathy can occur without preceding viremia. We also present two
      renal transplant recipients with persistent BK viruria, one with BKV-associated
      hemorrhagic cystitis and the other with microscopic hematuria. Therefore, we
      conclude that BKV manifestations may be more diverse than previously thought and
      suggest clinical utility in urine BKV qPCR testing in specific transplant
      recipients.

PMID- 23171067
TI  - An investigation of the auto-induction of and gender-related variability in the
      pharmacokinetics of dihydroartemisinin in the rat.
AB  - BACKGROUND: Artemisinin (QHS) and its derivatives dihydroartemisinin (DHA),
      artemether and artesunate have become the first-line anti-malarials in areas of
      multidrug resistance. Declining plasma concentrations during the repeated dosing
      have been reported for QHS, artemether and less convincingly for artesunate
      (ARS). However, there is limited information on whether the concentrations of
      their active metabolite DHA and its subsequent metabolites increased after
      multiple drug administrations. This study was designed to evaluate the potential
      auto-induction metabolism of DHA in animal species. The sex-specific effect on
      the pharmacokinetic profiles of DHA and its metabolites was studied. The
      pharmacokinetics of ARS, the prodrug of DHA, and its phase I/II metabolites were
      also investigated. METHODS: Two groups of rats received a single oral dose of DHA
      or ARS, and another two groups of rats were given oral doses of DHA or ARS once
      daily for five consecutive days. Plasma samples were analyzed for DHA, ARS and
      their phase I/II metabolites, using a validated liquid chromatography tandem mass
      spectrometric (LC-MS) method. RESULTS: DHA, monohydroxylated DHA (M1) and the
      glucuronide of DHA (DHA-G) were detected in rat plasma after oral administration
      of DHA or ARS. Neither DHA nor its metabolites (M1 and DHA-G) changed
      significantly (P > 0.05) in AUC0-t after 5-day oral doses of DHA or ARS. Sex
      difference was observed for DHA and its metabolites (M1 and DHA-G), whereas its
      prodrug ARS did not show similar characteristics for the corresponding
      metabolites (DHA, M1 and DHA-G). CONCLUSIONS: The results gave the direct
      evidence for the absence of auto-induction of phase I and phase II metabolism of
      DHA and ARS in rats. The sex effect existed for DHA but not for ARS, which could
      be caused by the sex-specific differences in absorption of DHA.

PMID- 23171068
TI  - Bilateral acromial dimples: a case report and review of the literature.
AB  - Bilateral acromial dimples are uncommon in pediatric dermatology. They are
      usually found as a sporadic finding with limited clinical symptoms but may cause
      concern for parents. They can occur spontaneously or be inherited. Bilateral
      acromial dimples may occasionally be present as part of more complex syndromes.
      This article reports an 18-month-old girl with congenital bilateral acromial
      dimples and presents a classification of this unusual entity. A literature review
      of English and non-English publications was performed. We report the second case
      of bilateral acromial dimples seen in the context of maternal cocaine use during
      pregnancy. Our case is probably sporadic and nonsyndromal. We suggest that
      bilateral acromial dimples be classified as syndromal or nonsyndromal and that
      nonsyndromal cases be subdivided into inherited and sporadic. Although bilateral
      acromial dimples can be seen in 18q deletion syndrome, Apert syndrome, Say
      syndrome, and a recently described syndrome in Brazil, our review of the
      literature does not support the association with trisomy 9 syndrome.
      Dermatologists need to be aware of this unusual cutaneous finding and potential
      syndromal associations. The significance of the association with fetal exposure
      to cocaine during pregnancy has yet to be determined. The biological mother was
      not available for assessment for bilateral acromial dimples. 

PMID- 23171069
TI  - Differential effects of selective and non-selective muscarinic antagonists on
      gastrointestinal transit and bowel function in healthy women.
AB  - BACKGROUND: The gastrointestinal effects of antimuscarinic drugs used to treat
      overactive bladder may be related to the selectivity of these agents for M(3) 
      muscarinic receptor subtypes. We compared the effects of non-selective
      (fesoterodine) and M(3)-selective (solifenacin) antimuscarinics on
      gastrointestinal transit in healthy women. METHODS: Gastric emptying (GE), small
      intestinal transit (colonic filling at 6 h), colonic transit [geometric center at
      24 h (GC24; primary endpoint) and 48 h (GC48)], and bowel habits were assessed by
      scintigraphy and bowel diaries before and after randomization to fesoterodine 8
      mg, solifenacin 10 mg, or placebo (2 : 2 : 1) for 14 days. An interim analysis to
      finalize sample size was conducted. KEY RESULTS: After 60 subjects [placebo (n =
      12), fesoterodine (n = 25), solifenacin (n = 23)] completed the study, the study
      was terminated due to a prespecified criterion (sample size >= 452.5 needed to
      provide >= 80% power to demonstrate superiority of fesoterodine over solifenacin
      in GC24). Compared with baseline, (i) placebo delayed small-intestinal, but not
      colonic, transit, (ii) fesoterodine significantly increased GE t(1/2) vs placebo
      (17.0 min; P = 0.027), and (iii) fesoterodine and solifenacin delayed small
      intestinal (-36.8% and -21.8%, respectively, P < 0.001 vs placebo) and colonic
      transit (GC24: -0.44 and -0.49, respectively, P < 0.05 vs placebo; GC48: -0.25
      and -0.65, respectively, P > 0.05 vs placebo). Solifenacin increased stool
      hardness from baseline (P = 0.010 for difference vs fesoterodine); stool
      frequency was comparable. CONCLUSIONS & INFERENCES: In healthy women,
      fesoterodine had greater effects on small-intestinal transit and solifenacin had
      greater effects on colonic transit; the latter finding may explain why
      solifenacin, but not fesoterodine, increased stool hardness.

PMID- 23171071
TI  - Valery (Chrom) Ivanov in memoriam.

PMID- 23171070
TI  - Romiplostim dose-response in patients with myelodysplastic syndromes.
AB  - AIM: To characterize the romiplostim dose-response in subjects with low or
      intermediate-1 risk myelodysplastic syndromes (MDS) receiving subcutaneous
      romiplostim. METHODS: Data from 44 MDS subjects receiving subcutaneous
      romiplostim (dose range 300-1500 MUg week(-1) ) were used to develop a
      pharmacodynamic model consisting of a romiplostim-sensitive progenitor cell
      compartment linked to the peripheral blood compartment through four transit
      compartments representing the maturation in the bone marrow from megakaryocytes
      to platelets. A kinetics of drug effect model was used to quantify the
      stimulatory effect of romiplostim on the proliferation of sensitive progenitor
      cells and pharmacodynamics-mediated disposition was modelled by assuming the
      kinetics of drug effect constant (kDE ) to be proportional to the change in
      platelet count relative to baseline. RESULTS: The estimated values (between
      subject variability) for baseline platelet count, mean transit time, and kDE were
      24 * 10(9) l(-1) (47%), 9.6 days (44%) and 0.28 days(-1) , respectively. MDS
      subjects had a shorter platelet lifespan (42 h) than healthy subjects (257 h).
      Romiplostim effect was described for responders (78%) and non-responders (22%).
      The average weekly stimulatory effect of romiplostim on the production rate of
      sensitive progenitor cells at baseline was 269% per 100 MUg week(-1) for
      responders. Body weight, age, gender and race were not statistically related to
      romiplostim pharmacodynamic parameters. Visual predictive checks confirmed the
      model adequacy. CONCLUSION: The time course of platelet counts in MDS subjects
      receiving subcutaneous administration of escalating doses of romiplostim was
      characterized and showed a linear dose-response for romiplostim responders to
      increase the platelet counts.

PMID- 23171072
TI  - Standard operating procedures for vascular surgery in erectile dysfunction:
      revascularization and venous procedures.
AB  - INTRODUCTION: The impact of penile blood supply on erectile function was
      recognized some 500 years ago. At the turn of the 20th century first results of
      penile venous ligation were published and in 1973 the first surgical attempts to
      restore penile arterial inflow were undertaken. Numerous techniques were
      published in the meantime, but inclusion criteria, patient selection, and success
      evaluation differed extremely between study groups. AIM: To develop evidence
      based standard operating procedures (SOPs) for vascular surgery in erectile
      dysfunction, based on recent state of the art consensus reports and recently
      published articles in peer-reviewed journals. METHODS: Based on the recent
      publication of the consensus process during the 2009 International Consultation
      on Sexual Medicine in Paris, recommendations are derived for diagnosis and
      surgical treatment of vascular erectile dysfunction. In addition several recent
      publications in this field not mentioned in the consensus statements are included
      in the discussion. MAIN OUTCOME MEASURE: The Oxford system of evidence-based
      review was systematically applied. Due to the generally low level of evidence in
      this field expert opinions were accepted, if published after a well-defined
      consensus process in peer-reviewed journals. RESULTS: Referring to penile
      revascularization it may be concluded, that in the face of missing randomized
      trials, only recommendations grade D may be given: this kind of surgery may be
      offered to men less than 55 years, who are nonsmokers, nondiabetic, and
      demonstrate isolated arterial stenoses in the absence of generalized vascular
      disease. The evidence level for recommendations concerning penile venous
      ligations may be even lower. Too many unsolved controversies exist and universal
      diagnostic criteria for patient selection as well as operative technique
      selection have not been unequivocally established. This kind of surgery is still
      considered investigational but may be offered in special situations on an
      individualized basis in an investigational or research setting after obtaining
      written consent, using both pre- and postoperatively validated measuring
      instruments of success evaluation. CONCLUSIONS: SOPs for penile revascularization
      procedures can be developed, concerning a highly selected patient group with
      isolated arterial stenoses. Based on the available data it is not yet possible to
      define SOPs for surgical treatment of corporal veno-occlusive dysfunction.

PMID- 23171073
TI  - Natural genetic variation in male reproductive genes contributes to
      nontransitivity of sperm competitive ability in Drosophila melanogaster.
AB  - Female Drosophila melanogaster frequently mate with multiple males, and the
      success of a given male depends not only on his genotype but also on the genotype
      of his competitor. Here, we assess how natural genetic variation affects male
      male interactions for traits influencing pre- and postcopulatory sexual
      selection. Males from a set of 66 chromosome substitution lines were competed
      against each other in a 'round-robin' design, and paternity was scored using bulk
      genotyping. We observed significant effects of the genotype of the first male to
      mate, the second male to mate and an interaction between the males for measures
      of male mating rate and sperm utilization. We also identified specific
      combinations of males who show nontransitive patterns of reproductive success and
      engage in 'rock-paper-scissors' games. We then tested for associations between
      245 polymorphisms in 32 candidate male reproductive genes and male reproductive
      success. We identified eight polymorphisms in six reproductive genes that
      associate with male reproductive success independent of the competitor
      (experimentwise P < 0.05). We also identified four SNPs in four different genes
      where the relative reproductive success of the alternative alleles changes
      depending on the competing males' genetic background (experimentwise P < 0.05);
      two of these associations include premature stop codons. This may be the first
      study that identifies the genes contributing to nontransitivity among males and
      further highlights that 'rock-paper-scissors' games could be an important
      evolutionary force maintaining genetic variation in natural populations.

PMID- 23171074
TI  - Arthroscopic cartilage regeneration facilitating procedure for osteoarthritic
      knee.
AB  - BACKGROUND: The effectiveness of arthroscopic treatment for osteoarthritic knee
      is a controversy. This study presents the technique of a novel concept of
      arthroscopic procedure and investigates its clinical outcome. METHOD: An
      arthroscopic procedure targeted on elimination of focal abrasion phenomenon and
      regaining soft tissue balance around patello-femoral joint was applied to treat
      osteoarthritis knees. Five hundred and seventy-one knees of 367 patients with
      osteoarthritis received this procedure. There were 70 (19%) male and 297 (81%)
      female and the mean age was 60 years (SD 10). The Knee Society score (KSS) and
      the knee injury and osteoarthritis outcome score (KOOS) were used for subjective
      outcome study. The roentgenographic changes of femoral-tibial angle and joint
      space width were evaluated for objective outcomes. The mean follow-up period was
      38 months (SD 3). RESULTS: There were 505 knees in 326 patients available with
      more than 3 years follow-up and the mean follow-up period was 38 months (SD 3).
      The subjective satisfactory rate for the whole series was 85.5%. For 134 knees
      with comprehensive follow-up evaluation, the KSS and all subscales of the KOOS
      improved statistically. The femoral-tibial angle improved from 1.57 degrees (SD
      3.92) to 1.93 degrees (SD 4.12) (mean difference: 0.35, SD 0.17). The joint space
      width increased from 2.02 millimeters (SD 1.24) to 2.17 millimeters (SD 1.17)
      (mean difference: 0.13, SD 0.05). The degeneration process of the medial
      compartment was found being reversed in 82.1% of these knees by radiographic
      evaluation. CONCLUSIONS: Based on these observations arthroscopic cartilage
      regeneration facilitating procedure is an effective treatment for osteoarthritis
      of the knee joint and can be expected to satisfy the majority of patients and
      reverse the degenerative process of their knees.

PMID- 23171075
TI  - Inhibition of dengue NS2B-NS3 protease and viral replication in Vero cells by
      recombinant retrocyclin-1.
AB  - BACKGROUND: Global resurgence of dengue virus infections in many of the tropical
      and subtropical countries is a major concern. Therefore, there is an urgent need
      for the development of successful drugs that are both economical and offer a long
      lasting protection. The viral NS2B-NS3 serine protease (NS2B-NS3pro) is a
      promising target for the development of drug-like inhibitors, which are not
      available at the moment. In this study, we report retrocyclin-1 (RC-1) production
      in E. coli as a recombinant peptide to test against dengue NS2B-NS3pro. METHODS:
      Dengue NS2B-NS3pro was produced as a recombinant single chain protein in E. coli
      and purified by Ni+ affinity chromatography. The RC-1 peptide was produced in E.
      coli and the tri-disulphide bonds were reformed in a diluted alkaline
      environment. Protease assay was performed using a fluorogenic peptide substrate
      and measured by fluorescence spectrometry. Real-time PCR was used for
      quantification of dengue serotype 2 (DENV-2) viral RNA produced in Vero cells.
      RESULTS: The RC-1 peptide inhibited the activity of recombinant NS2B-NS3pro with
      different values at 50% inhibitory concentration (IC50) which are temperature
      dependent (28 degrees C, 46.1 +/- 1.7 MUM; 37 degrees C, 21.4 +/- 1.6 MUM; 40
      degrees C, 14.1 +/- 1.2 MUM). The presence of RC-1 significantly reduced viral
      replication in Vero cells infected with DENV-2 at simultaneous treatment after 48
      hrs (70%) and 75 hrs (85%). Furthermore, moderate reduction in viral replication
      was observed at pre-treatment mode after 48 hrs (40%) and 72 hrs (38%) and post
      treatment at 48 hrs (30%) and 72 hrs (45%). CONCLUSION: Recombinant RC-1 inhibits
      DENV-2 replication in Vero cells by interfering with the activity of its serine
      protease. Thus, we propose that recombinant RC-1 is a potent, cost-effective
      dengue virus inhibitor. Therefore, it is suitable to consider RC-1 as a new
      candidate for drug development against dengue infection.

PMID- 23171076
TI  - Knowledge and performance of the Ethiopian health extension workers on antenatal
      and delivery care: a cross-sectional study.
AB  - BACKGROUND: In recognition of the critical shortage of human resources within
      health services, community health workers have been trained and deployed to
      provide primary health care in developing countries. However, very few studies
      have investigated whether these health workers can provide good quality of care.
      This study investigated the knowledge and performance of health extension workers
      (HEWs) on antenatal and delivery care. The study also explored the barriers and
      facilitators for HEWs in the provision of maternal health care. METHODS: In
      conducting this research, a cross-sectional study was performed. A total of 50
      HEWs working in 39 health posts, covering a population of approximately 195,000
      people, were interviewed. Descriptive statistics was used and a composite score
      of knowledge of HEWs was made and interpreted based on the Ethiopian education
      scoring system. RESULTS: Almost half of the respondents had at least 5 years of
      work experience as a HEW. More than half (27 (54%)) of the HEWs had poor
      knowledge on contents of antenatal care counseling, and the majority (44 (88%))
      had poor knowledge on danger symptoms, danger signs, and complications in
      pregnancy. Health posts, which are the operational units for HEWs, did not have
      basic infrastructures like water supply, electricity, and waiting rooms for women
      in labor. On average within 6 months, a HEW assisted in 5.8 births. Only a few
      births (10%) were assisted at the health posts, the majority (82%) were assisted
      at home and only 20% of HEWs received professional assistance from a midwife.
      CONCLUSION: Considering the poor knowledge of HEWs, poorly equipped health posts,
      and poor referral systems, it is difficult for HEWs to play a key role in
      improving health facility deliveries, skilled birth attendance, and on-time
      referral through early identification of danger signs. Hence, there is an urgent
      need to design appropriate strategies to improve the performance of HEWs by
      enhancing their knowledge and competencies, while creating appropriate working
      conditions.

PMID- 23171077
TI  - Long-term results of radiotherapy combined with nedaplatin and 5-fluorouracil for
      postoperative loco-regional recurrent esophageal cancer: update on a phase II
      study.
AB  - BACKGROUND: In 2006, we reported the effectiveness of chemoradiotherapy for
      postoperative recurrent esophageal cancer with a median observation period of 18
      months. The purpose of the present study was to update the results of
      radiotherapy combined with nedaplatin and 5-fluorouracil (5-FU) for postoperative
      loco-regional recurrent esophageal cancer. METHODS: Between 2000 and 2004, we
      performed a phase II study on treatment of postoperative loco-regional recurrent
      esophageal cancer with radiotherapy (60 Gy/30 fractions/6 weeks) combined with
      chemotherapy consisting of two cycles of nedaplatin (70 mg/m2/2 h) and 5-FU (500
      mg/m2/24 h for 5 days).The primary endpoint was overall survival rate, and the
      secondary endpoints were progression-free survival rate, irradiated-field control
      rate and chronic toxicity. RESULTS: A total of 30 patients were enrolled in this
      study. The regimen was completed in 76.7% of the patients. The median observation
      period for survivors was 72.0 months. The 5-year overall survival rate was 27.0%
      with a median survival period of 21.0 months. The 5-year progression-free
      survival rate and irradiated-field control rate were 25.1% and 71.5%,
      respectively. Grade 3 or higher late toxicity was observed in only one patient.
      Two long-term survivors had gastric tube cancer more than 5 years after
      chemoradiotherapy.Pretreatment performance status, pattern of recurrence (worse
      for patients with anastomotic recurrence) and number of recurrent lesions (worse
      for patients with multiple recurrent lesions) were statistically significant
      prognostic factors for overall survival. CONCLUSIONS: Radiotherapy combined with
      nedaplatin and 5-FU is a safe and effective salvage treatment for postoperative
      loco-regional recurrent esophageal cancer. However, the prognosis of patients
      with multiple regional recurrence or anastomotic recurrence is very poor.

PMID- 23171079
TI  - Toward inexpensive superhard materials: tungsten tetraboride-based solid
      solutions.
AB  - To enhance the hardness of tungsten tetraboride (WB(4)), a notable lower cost
      member of the late transition-metal borides, we have synthesized and
      characterized solid solutions of this material with tantalum (Ta), manganese
      (Mn), and chromium (Cr). Various concentrations of these transition-metal
      elements, ranging from 0.0 to 50.0 at. %, on a metals basis, were made. Arc
      melting was used to synthesize these refractory compounds from the pure elements.
      Elemental and phase purity of the samples were examined using energy-dispersive X
      ray spectroscopy (EDS) and X-ray diffraction (XRD), and microindentation was
      utilized to measure the Vickers hardness under applied loads of 0.49-4.9 N. XRD
      results indicate that the solubility limit is below 10 at. % for Cr and below 20
      at. % for Mn, while Ta is soluble in WB(4) above 20 at. %. Optimized Vickers
      hardness values of 52.8 +/- 2.2, 53.7 +/- 1.8, and 53.5 +/- 1.9 GPa were
      achieved, under an applied load of 0.49 N, when ~2.0, 4.0, and 10.0 at. % Ta, Mn,
      and Cr were added to WB(4) on a metals basis, respectively. Motivated by these
      results, ternary solid solutions of WB(4) were produced, keeping the
      concentration of Ta in WB(4) fixed at 2.0 at. % and varying the concentration of
      Mn or Cr. This led to hardness values of 55.8 +/- 2.3 and 57.3 +/- 1.9 GPa (under
      a load of 0.49 N) for the combinations W(0.94)Ta(0.02)Mn(0.04)B(4) and
      W(0.93)Ta(0.02)Cr(0.05)B(4), respectively. In situ high-pressure XRD measurements
      collected up to ~65 GPa generated a bulk modulus of 335 +/- 3 GPa for the hardest
      WB(4) solid solution, W(0.93)Ta(0.02)Cr(0.05)B(4), and showed suppression of a
      pressure-induced phase transition previously observed in pure WB(4).

PMID- 23171080
TI  - Early Wallerian degeneration on magnetic resonance imaging: underappreciated but
      highly relevant.

PMID- 23171081
TI  - Strong carrier lifetime enhancement in GaAs nanowires coated with semiconducting
      polymer.
AB  - The ultrafast charge carrier dynamics in GaAs/conjugated polymer type II
      heterojunctions are investigated using time-resolved photoluminescence
      spectroscopy at 10 K. By probing the photoluminescence at the band edge of GaAs,
      we observe strong carrier lifetime enhancement for nanowires blended with
      semiconducting polymers. The enhancement is found to depend crucially on the
      ionization potential of the polymers with respect to the Fermi energy level at
      the surface of the GaAs nanowires. We attribute these effects to electron doping
      by the polymer which reduces the unsaturated surface-state density in GaAs. We
      find that when the surface of nanowires is terminated by native oxide, the
      electron injection across the interface is greatly reduced and such surface
      doping is absent. Our results suggest that surface engineering via pi-conjugated
      polymers can substantially improve the carrier lifetime in nanowire hybrid
      heterojunctions with applications in photovoltaics and nanoscale photodetectors.

PMID- 23171078
TI  - Nuclear genomic control of naturally occurring variation in mitochondrial
      function in Drosophila melanogaster.
AB  - BACKGROUND: Mitochondria are organelles found in nearly all eukaryotic cells that
      play a crucial role in cellular survival and function. Mitochondrial function is
      under the control of nuclear and mitochondrial genomes. While the latter has been
      the focus of most genetic research, we remain largely ignorant about the nuclear
      encoded genomic control of inter-individual variability in mitochondrial
      function. Here, we used Drosophila melanogaster as our model organism to address
      this question. RESULTS: We quantified mitochondrial state 3 and state 4
      respiration rates and P:O ratio in mitochondria isolated from the thoraces of 40
      sequenced inbred lines of the Drosophila Genetic Reference Panel. We found
      significant within-population genetic variability for all mitochondrial traits.
      Hence, we performed genome-wide association mapping and identified 141 single
      nucleotide polymorphisms (SNPs) associated with differences in mitochondrial
      respiration and efficiency (P <=1 * 10-5). Gene-centered regression models showed
      that 2-3 SNPs can explain 31, 13, and 18% of the phenotypic variation in state 3,
      state 4, and P:O ratio, respectively. Most of the genes tagged by the SNPs are
      involved in organ development, second messenger-mediated signaling pathways, and
      cytoskeleton remodeling. One of these genes, sallimus (sls), encodes a component
      of the muscle sarcomere. We confirmed the direct effect of sls on mitochondrial
      respiration using two viable mutants and their coisogenic wild-type strain.
      Furthermore, correlation network analysis revealed that sls functions as a
      transcriptional hub in a co-regulated module associated with mitochondrial
      respiration and is connected to CG7834, which is predicted to encode a protein
      with mitochondrial electron transfer flavoprotein activity. This latter finding
      was also verified in the sls mutants. CONCLUSIONS: Our results provide novel
      insights into the genetic factors regulating natural variation in mitochondrial
      function in D. melanogaster. The integrative genomic approach used in our study
      allowed us to identify sls as a novel hub gene responsible for the regulation of
      mitochondrial respiration in muscle sarcomere and to provide evidence that sls
      might act via the electron transfer flavoprotein/ubiquinone oxidoreductase
      complex.

PMID- 23171082
TI  - Single-walled carbon nanotubes alter cytochrome c electron transfer and modulate
      mitochondrial function.
AB  - Single-walled carbon nanotubes (SWCNTs) are broadly used for various biomedical
      applications such as drug delivery, in vivo imaging, and cancer photothermal
      therapy due to their unique physiochemical properties. However, once they enter
      the cells, the effects of SWCNTs on the intracellular organelles and
      macromolecules are not comprehensively understood. Cytochrome c (Cyt c), as a key
      component of the electron transport chain in mitochondria, plays an essential
      role in cellular energy consumption, growth, and differentiation. In this study,
      we found the mitochondrial membrane potential and mitochondrial oxygen uptake
      were greatly decreased in human epithelial KB cells treated with SWCNTs, which
      accompanies the reduction of Cyt c. SWCNTs deoxidized Cyt c in a pH-dependent
      manner, as evidenced by the appearance of a 550 nm characteristic absorption
      peak, the intensity of which increased as the pH increased. Circular dichroism
      measurement confirmed the pH-dependent conformational change, which facilitated
      closer association of SWCNTs with the heme pocket of Cyt c and thus expedited the
      reduction of Cyt c. The electron transfer of Cyt c is also disturbed by SWCNTs,
      as measured with electron spin resonance spectroscopy. In conclusion, the redox
      activity of Cyt c was affected by SWCNTs treatment due to attenuated electron
      transfer and conformational change of Cyt c, which consequently changed
      mitochondrial respiration of SWCNTs-treated cells. This work is significant to
      SWCNTs research because it provides a novel understanding of SWCNTs' disruption
      of mitochondria function and has important implications for biomedical
      applications of SWCNTs.

PMID- 23171083
TI  - Clinicopathological and molecular aspects of foregut gastrointestinal stromal
      tumours.
AB  - BACKGROUND: Gastrointestinal stromal tumours (GISTs) are the most common
      gastrointestinal mesenchymal tumour. This study describes clinicopathological and
      molecular characteristics in association with clinical outcome, in patients
      undergoing foregut GIST resection. METHODS: Clinicopathological data were
      collated retrospectively for 40 consecutive foregut GISTs. Mutational analysis
      (quantitative polymerase chain reaction) for KIT exons 9, 11, 13 and 17 and
      PDGFRa exon 18 was performed on paraffin-embedded tissue (40 primary tumours and
      three metastases). RESULTS: The median age was 63 years (range: 40-92), and
      melaena was the most common presentation (30%). Patients undergoing a totally
      laparoscopic excision had the shortest mean hospital stay (5.5 days). Over a
      median of 72-month follow-up, seven patients developed recurrence/metastases.
      Tumour size and mitotic rate correlated with recurrence (P < 0.01; <0.01) and
      mortality (P = 0.03; <0.01). KIT (23/40) or PDGFRa (12/40) mutations were found
      in 87.5% of the primary tumours. Only patients with KIT mutations suffered
      mortality (n = 4; P = 0.19) and no patient with a PDGFRa developed recurrence (P
      = 0.13). CONCLUSIONS: Tumour site, size and mitotic rate were confirmed as
      prognostic markers. While KIT and PDGFRa mutations were associated with negative
      and positive outcomes, respectively, this did not prove to be significant. The
      clinical impact of these findings may only become apparent in larger series.

PMID- 23171084
TI  - Rather than by direct acquisition via lateral gene transfer, GHF5 cellulases were
      passed on from early Pratylenchidae to root-knot and cyst nematodes.
AB  - BACKGROUND: Plant parasitic nematodes are unusual Metazoans as they are equipped
      with genes that allow for symbiont-independent degradation of plant cell walls.
      Among the cell wall-degrading enzymes, glycoside hydrolase family 5 (GHF5)
      cellulases are relatively well characterized, especially for high impact
      parasites such as root-knot and cyst nematodes. Interestingly, ancestors of
      extant nematodes most likely acquired these GHF5 cellulases from a prokaryote
      donor by one or multiple lateral gene transfer events. To obtain insight into the
      origin of GHF5 cellulases among evolutionary advanced members of the order
      Tylenchida, cellulase biodiversity data from less distal family members were
      collected and analyzed. RESULTS: Single nematodes were used to obtain (partial)
      genomic sequences of cellulases from representatives of the genera Meloidogyne,
      Pratylenchus, Hirschmanniella and Globodera. Combined Bayesian analysis of ~ 100
      cellulase sequences revealed three types of catalytic domains (A, B, and C).
      Represented by 84 sequences, type B is numerically dominant, and the overall
      topology of the catalytic domain type shows remarkable resemblance with trees
      based on neutral (= pathogenicity-unrelated) small subunit ribosomal DNA
      sequences. Bayesian analysis further suggested a sister relationship between the
      lesion nematode Pratylenchus thornei and all type B cellulases from root-knot
      nematodes. Yet, the relationship between the three catalytic domain types
      remained unclear. Superposition of intron data onto the cellulase tree suggests
      that types B and C are related, and together distinct from type A that is
      characterized by two unique introns. CONCLUSIONS: All Tylenchida members
      investigated here harbored one or multiple GHF5 cellulases. Three types of
      catalytic domains are distinguished, and the presence of at least two types is
      relatively common among plant parasitic Tylenchida. Analysis of coding sequences
      of cellulases suggests that root-knot and cyst nematodes did not acquire this
      gene directly by lateral genes transfer. More likely, these genes were passed on
      by ancestors of a family nowadays known as the Pratylenchidae.

PMID- 23171085
TI  - Bidirectional asynchronous arterial flow in monochorionic twins--a precursor to
      the twin reverse arterial perfusion sequence.

PMID- 23171086
TI  - Connecting the chemical and biological reactivity of epoxides.
AB  - The chemical reactivity of the mutagenic epoxides (EP) propylene oxide (PO), 1,2
      epoxybutane (1,2-EB), and cis- and trans-2,3-epoxybutane (cis- and trans-2,3-EB)
      with 4-(p-nitrobenzyl)pyridine (NBP), a bionucleophile model for S(N)2 alkylating
      agents with high affinity for the guanine-N7 position, was investigated
      kinetically. It was found that three reactions are involved simultaneously: the
      alkylation reaction of NBP by EP, which yields the corresponding NBP-EP adducts
      through an S(N)2 mechanism, and EP and NBP-EP hydrolysis reactions. PO and 1,2-EB
      were seen to exhibit a higher alkylating potential than cis- and trans-2,3-EB.
      From a study of the correlations between the chemical reactivity (kinetic
      parameters) and the biological effectiveness of oxiranes, the following
      conclusions can be drawn: (i) the hydrolysis reactions of epoxides must be taken
      into account to understand their bioactivity. (ii) The fraction (f) of the
      alkylating oxirane that forms the adduct and the adduct life (AL) permit the
      potential of epoxides as bioactive molecules to be rationalized even
      semiquantitatively; and (iii) alkylation of DNA by epoxides and the O(6)-/N7
      guanine adduct ratio are directly related to their mutagenicity in vitro.

PMID- 23171087
TI  - The response regulator SypE controls biofilm formation and colonization through
      phosphorylation of the syp-encoded regulator SypA in Vibrio fischeri.
AB  - Bacteria utilize multiple regulatory systems to modulate gene expression in
      response to environmental changes, including two-component signalling systems and
      partner-switching networks. We recently identified a novel regulatory protein,
      SypE, that combines features of both signalling systems. SypE contains a central
      response regulator receiver domain flanked by putative kinase and phosphatase
      effector domains with similarity to partner-switching proteins. SypE was
      previously shown to exert dual control over biofilm formation through the
      opposing activities of its terminal effector domains. Here, we demonstrate that
      SypE controls biofilms in Vibrio fischeri by regulating the activity of SypA, a
      STAS (sulphate transporter and anti-sigma antagonist) domain protein. Using
      biochemical and genetic approaches, we determined that SypE both phosphorylates
      and dephosphorylates SypA, and that phosphorylation inhibits SypA's activity.
      Furthermore, we found that biofilm formation and symbiotic colonization required
      active, unphosphorylated SypA, and thus SypA phosphorylation corresponded with a
      loss of biofilms and impaired host colonization. Finally, expression of a non
      phosphorylatable mutant of SypA suppressed both the biofilm and symbiosis defects
      of a constitutively inhibitory SypE mutant strain. This study demonstrates that
      regulation of SypA activity by SypE is a critical mechanism by which V. fischeri
      controls biofilm development and symbiotic colonization.

PMID- 23171088
TI  - HIV-1 co-receptor expression and epithelial immune cells of the cervix in
      asymptomatic women attending a genitourinary medicine clinic.
AB  - OBJECTIVES: The aim of the study was to qualitatively and semiquantitatively
      characterize the expression of the principal HIV co-receptors chemokine (C-C
      motif) receptor 5 (CCR5) and chemokine (C-X-C motif) receptor 4 (CXCR4) on
      susceptible CD4 T-helper cell, monocyte/macrophage and Langerhans dendritic cell
      populations within the cervical epithelia of asymptomatic women attending a
      genitourinary medicine clinic. METHODS: Of 77 asymptomatic women recruited, 35
      were excluded: 21 because they were found to have bacterial vaginosis, eight
      because they were found to have candida and six for other reasons. Cervical
      cytobrush samples from 11 women with Chlamydia trachomatis infection and 31 women
      without any detectable genital infection were stained with fluorescently labelled
      antibodies specific for cell surface CCR5, CXCR4, CD4, CD3, CD1a and CD19
      expression, then analysed by flow cytometry. RESULTS: CD4/CD3 T-helper cells
      (84%), CD1a Langerhans dendritic cells (75%) and CD4/CD14 monocytes/macrophages
      (59%) were detected in the samples. CCR5 and CXCR4 HIV co-receptor expression was
      observed on 46-86% of the above subsets. CD1a cells exhibited significantly
      higher CCR5 and CXCR4 positivity and median fluorescence than CD4 cells and
      higher CXCR4 positivity and median fluorescence than CD14 cells (P < 0.05 or
      less). Increased detection of CCR5 over CXCR4 was seen in CD14 cells (P < 0.05).
      No significant differences in CCR5 or CXCR4 expression were found in samples from
      asymptomatic women with or without chlamydial infection. CONCLUSIONS: Co-receptor
      expression confirms the potential for CD1a Langerhans cells,
      monocytes/macrophages and T-helper cells in the cervix as primary targets for HIV
      infection. Previously observed selective transmission of CCR5-tropic isolates
      cannot be accounted for by a lack of CXCR4-expressing CD4 cervical immune cells.
      We were unable to identify any specific impact of chlamydial infection on co
      receptor expression in this study.

PMID- 23171089
TI  - Visceral and somatic sensory function in functional dyspepsia.
AB  - BACKGROUND: Visceral hypersensitivity is one of the proposed underlying
      mechanisms in functional dyspepsia (FD). It is not clear whether visceral
      hypersensitivity in FD is a manifestation of a central sensitization also
      encompassing somatic sensitization. Transient receptor potential vanilloid-1
      (TRPV(1)) pathways are involved in gastric mechanosensory physiology and the
      TRPV(1) receptor agonist, capsaicin, has been used as a chemical stimulant.
      METHODS: In this double-blind, randomized study we evaluated both visceral and
      somatic sensory function in 34 FD patients and 42 healthy controls using
      quantitative sensory testing. Visceral pain sensitivity was assessed using a
      validated gastric pain model with oral capsaicin capsule titration and somatic
      pain sensitivity was determined by foot heat and hand electric stimulation. KEY
      RESULTS: The median capsaicin dose required to attain moderate pain was 0.5mg in
      FD and 1mg in controls (P = 0.03). At these doses, mean pain intensities on a 0
      100 visual analog scale were greater for FD than controls [56.9 (95% confidence
      intervals, 52.2-61.5) vs 45.1 (41.6-48.6), resp.] (P = 0.005). Overall, mean
      somatic sensory and pain thresholds were similar in FD and control groups, but in
      a subgroup of FD pain hypersensitivity was seen on the hand and on the foot at
      different stimulation thresholds. CONCLUSIONS & INFERENCES: A majority of
      patients with FD have visceral chemo-hypersensitivity involving TRPV(1) pathways.
      A substantial subgroup also has somatic hypersensitivity as evidence of central
      sensitization.

PMID- 23171090
TI  - Triazolyl donor/acceptor chromophore decorated unnatural nucleosides and
      oligonucleotides with duplex stability comparable to that of a natural
      adenine/thymine pair.
AB  - We report the design and synthesis of triazolyl donor/acceptor unnatural
      nucleosides via click chemistry and studies on the duplex stabilization of DNA
      containing two such new nucleosides. The observed duplex stabilization among the
      self-pair/heteropair has been found to be comparable to that of a natural A/T
      pair. Our observations on the comparable duplex stabilization has been explained
      on the basis of possible pi-pi stacking and/or charge transfer interactions
      between the pairing partners. The evidence of ground-state charge transfer
      complexation came from the UV-vis spectra and the static quenching of
      fluorescence in a heteropair. We have also exploited one of our unnatural DNAs in
      stabilizing abasic DNA.

PMID- 23171091
TI  - Pulsed radio frequency. But what dose did you use?

PMID- 23171092
TI  - Drug policy for an aging population--the European Medicines Agency's geriatric
      medicines strategy.

PMID- 23171093
TI  - Intensive care in low-income countries--a critical need.

PMID- 23171094
TI  - Confronting the social determinants of health--obesity, neglect, and inequity.

PMID- 23171096
TI  - Effect of three decades of screening mammography on breast-cancer incidence.
AB  - BACKGROUND: To reduce mortality, screening must detect life-threatening disease
      at an earlier, more curable stage. Effective cancer-screening programs therefore
      both increase the incidence of cancer detected at an early stage and decrease the
      incidence of cancer presenting at a late stage. METHODS: We used Surveillance,
      Epidemiology, and End Results data to examine trends from 1976 through 2008 in
      the incidence of early-stage breast cancer (ductal carcinoma in situ and
      localized disease) and late-stage breast cancer (regional and distant disease)
      among women 40 years of age or older. RESULTS: The introduction of screening
      mammography in the United States has been associated with a doubling in the
      number of cases of early-stage breast cancer that are detected each year, from
      112 to 234 cases per 100,000 women--an absolute increase of 122 cases per 100,000
      women. Concomitantly, the rate at which women present with late-stage cancer has
      decreased by 8%, from 102 to 94 cases per 100,000 women--an absolute decrease of
      8 cases per 100,000 women. With the assumption of a constant underlying disease
      burden, only 8 of the 122 additional early-stage cancers diagnosed were expected
      to progress to advanced disease. After excluding the transient excess incidence
      associated with hormone-replacement therapy and adjusting for trends in the
      incidence of breast cancer among women younger than 40 years of age, we estimated
      that breast cancer was overdiagnosed (i.e., tumors were detected on screening
      that would never have led to clinical symptoms) in 1.3 million U.S. women in the
      past 30 years. We estimated that in 2008, breast cancer was overdiagnosed in more
      than 70,000 women; this accounted for 31% of all breast cancers diagnosed.
      CONCLUSIONS: Despite substantial increases in the number of cases of early-stage
      breast cancer detected, screening mammography has only marginally reduced the
      rate at which women present with advanced cancer. Although it is not certain
      which women have been affected, the imbalance suggests that there is substantial
      overdiagnosis, accounting for nearly a third of all newly diagnosed breast
      cancers, and that screening is having, at best, only a small effect on the rate
      of death from breast cancer.

PMID- 23171098
TI  - Intravenous immune globulin in autoimmune and inflammatory diseases.

PMID- 23171097
TI  - Medication for attention deficit-hyperactivity disorder and criminality.
AB  - BACKGROUND: Attention deficit-hyperactivity disorder (ADHD) is a common disorder
      that has been associated with criminal behavior in some studies. Pharmacologic
      treatment is available for ADHD and may reduce the risk of criminality. METHODS:
      Using Swedish national registers, we gathered information on 25,656 patients with
      a diagnosis of ADHD, their pharmacologic treatment, and subsequent criminal
      convictions in Sweden from 2006 through 2009. We used stratified Cox regression
      analyses to compare the rate of criminality while the patients were receiving
      ADHD medication, as compared with the rate for the same patients while not
      receiving medication. RESULTS: As compared with nonmedication periods, among
      patients receiving ADHD medication, there was a significant reduction of 32% in
      the criminality rate for men (adjusted hazard ratio, 0.68; 95% confidence
      interval [CI], 0.63 to 0.73) and 41% for women (hazard ratio, 0.59; 95% CI, 0.50
      to 0.70). The rate reduction remained between 17% and 46% in sensitivity analyses
      among men, with factors that included different types of drugs (e.g., stimulant
      vs. nonstimulant) and outcomes (e.g., type of crime). CONCLUSIONS: Among patients
      with ADHD, rates of criminality were lower during periods when they were
      receiving ADHD medication. These findings raise the possibility that the use of
      medication reduces the risk of criminality among patients with ADHD. (Funded by
      the Swedish Research Council and others.).

PMID- 23171099
TI  - Images in clinical medicine. Anaphylaxis associated with blue dye.

PMID- 23171100
TI  - Case records of the Massachusetts General Hospital. Case 36-2012. Recovery of a
      16-year-old girl from trauma and burns after a car accident.

PMID- 23171101
TI  - Is the dream of EVAR over?

PMID- 23171102
TI  - Residents' duty hours--toward an empirical narrative.

PMID- 23171095
TI  - Long-term comparison of endovascular and open repair of abdominal aortic
      aneurysm.
AB  - BACKGROUND: Whether elective endovascular repair of abdominal aortic aneurysm
      reduces long-term morbidity and mortality, as compared with traditional open
      repair, remains uncertain. METHODS: We randomly assigned 881 patients with
      asymptomatic abdominal aortic aneurysms who were candidates for both procedures
      to either endovascular repair (444) or open repair (437) and followed them for up
      to 9 years (mean, 5.2). Patients were selected from 42 Veterans Affairs medical
      centers and were 49 years of age or older at the time of registration. RESULTS:
      More than 95% of the patients underwent the assigned repair. For the primary
      outcome of all-cause mortality, 146 deaths occurred in each group (hazard ratio
      with endovascular repair versus open repair, 0.97; 95% confidence interval [CI],
      0.77 to 1.22; P=0.81). The previously reported reduction in perioperative
      mortality with endovascular repair was sustained at 2 years (hazard ratio, 0.63;
      95% CI, 0.40 to 0.98; P=0.04) and at 3 years (hazard ratio, 0.72; 95% CI, 0.51 to
      1.00; P=0.05) but not thereafter. There were 10 aneurysm-related deaths in the
      endovascular-repair group (2.3%) versus 16 in the open-repair group (3.7%)
      (P=0.22). Six aneurysm ruptures were confirmed in the endovascular-repair group
      versus none in the open-repair group (P=0.03). A significant interaction was
      observed between age and type of treatment (P=0.006); survival was increased
      among patients under 70 years of age in the endovascular-repair group but tended
      to be better among those 70 years of age or older in the open-repair group.
      CONCLUSIONS: Endovascular repair and open repair resulted in similar long-term
      survival. The perioperative survival advantage with endovascular repair was
      sustained for several years, but rupture after repair remained a concern.
      Endovascular repair led to increased long-term survival among younger patients
      but not among older patients, for whom a greater benefit from the endovascular
      approach had been expected. (Funded by the Department of Veterans Affairs Office
      of Research and Development; OVER ClinicalTrials.gov number, NCT00094575.).

PMID- 23171104
TI  - Clinical and biomarker changes in Alzheimer's disease.

PMID- 23171105
TI  - Clinical and biomarker changes in Alzheimer's disease.

PMID- 23171106
TI  - Clinical and biomarker changes in Alzheimer's disease.

PMID- 23171108
TI  - Enzymatic vitreolysis with ocriplasmin for vitreomacular traction and macular
      holes.

PMID- 23171109
TI  - Enzymatic vitreolysis with ocriplasmin for vitreomacular traction and macular
      holes.

PMID- 23171110
TI  - Enzymatic vitreolysis with ocriplasmin for vitreomacular traction and macular
      holes.

PMID- 23171112
TI  - Prevention of leukemia relapse by donor activating KIR2DS1.

PMID- 23171114
TI  - Eltrombopag before procedures in patients with cirrhosis and thrombocytopenia.

PMID- 23171115
TI  - Eltrombopag before procedures in patients with cirrhosis and thrombocytopenia.

PMID- 23171116
TI  - Flaws in the Medicare readmission penalty.

PMID- 23171117
TI  - Variola virus in a 300-year-old Siberian mummy.

PMID- 23171120
TI  - Images in clinical medicine. Idiopathic aqueductal stenosis.

PMID- 23171121
TI  - Clinical decisions. Mammography screening for breast cancer.

PMID- 23171122
TI  - The critical aggregation concentration of peptide surfactants is predictable from
      dynamic hydrophobic property.
AB  - Peptide surfactants are a kind of newly emerged functional materials, which have
      a variety of applications such as building nanoarchitecture, stabilizing membrane
      proteins and controlling drug release. In the present study, we report the
      modelling and prediction of critical aggregation concentration (CAC), an
      important parameter that characterizes the self-assembling behaviour of peptide
      surfactants through the use of statistical modelling and quantitative structure
      property relationship (QSPR) approaches. In order to accurately describe the
      structural and physicochemical properties of the highly flexible peptide
      molecules, a new method called molecular dynamics-based hydrophobic cross-field
      (MD-HCF) is proposed to capture both the hydrophobic profile and dynamic feature
      of 32 surface-activity, structure-known peptides. A number of statistical models
      are then developed using partial least squares (PLS) regression with or without
      improvement by genetic algorithm (GA). We demonstrate that MD-HCF performs much
      better than the widely used CODESSA method in both its predictability and
      interpretability. We also highlight the importance of dynamic hydrophobic
      property in accurate prediction and reasonable explanation of peptide self
      assembling behaviour in solution, albeit which is exhaustive to compute compared
      with those derived directly from peptide static structure. To the best of our
      knowledge, this study is the first to computationally model and predict the self
      assembling behaviour of peptide surfactants.

PMID- 23171124
TI  - Quantitative description of temperature induced self-aggregation thermograms
      determined by differential scanning calorimetry.
AB  - A novel thermodynamic approach for the description of differential scanning
      calorimetry (DSC) experiments on self-aggregating systems is derived and
      presented. The method is based on a mass action model where temperature
      dependence of aggregation numbers is considered. The validity of the model was
      confirmed by describing the aggregation behavior of poly(ethylene oxide)
      poly(propylene oxide) block copolymers, which are well-known to exhibit a strong
      temperature dependence. The quantitative description of the thermograms could be
      performed without any discrepancy between calorimetric and van 't Hoff
      enthalpies, and moreover, the aggregation numbers obtained from the best fit of
      the DSC experiments are in good agreement with those obtained by light scattering
      experiments corroborating the assumptions done in the derivation of the new
      model.

PMID- 23171123
TI  - Entomological indices of malaria transmission in Chikhwawa district, Southern
      Malawi.
AB  - BACKGROUND: Although malaria is highly prevalent throughout Malawi, little is
      known of its transmission dynamics. This paper describes the seasonal activity of
      the different vectors, human biting indices, sporozoite rates and the
      entomological inoculation rate in a low-lying rural area in southern Malawi.
      METHODS: Vectors were sampled over 52 weeks from January 2002 to January 2003, by
      pyrethrum knockdown catch in two villages in Chikhwawa district, in the Lower
      Shire Valley. RESULTS: In total, 7,717 anophelines were collected of which 55.1%
      were Anopheles gambiae sensu lato and 44.9% were Anopheles funestus. Three
      members of the An. gambiae complex were identified by PCR: Anopheles arabiensis
      (75%) was abundant throughout the year, An. gambiae s.s. (25%) was most common
      during the wet season and Anopheles quadriannulatus occurred at a very low
      frequency (n=16). An. funestus was found in all samples but was most common
      during the dry season.Anopheles gambiae s.s. and An. funestus were highly
      anthropophilic with human blood indices of 99.2% and 96.3%, respectively.
      Anopheles arabiensis had fed predominantly on humans (85.0%) and less commonly on
      cattle (10.9%; 1.2% of blood meals were of mixed origin). Plasmodium falciparum
      (192/3,984) and Plasmodium malariae (1/3,984) sporozoites were detected by PCR in
      An. arabiensis (3.2%) and An. funestus (4.5%), and in a significantly higher
      proportion of An. gambiae s.s. (10.6%)(p<0.01). All three vectors were present
      throughout the year and malaria transmission occurred in every month, although
      with greatest intensity during the rainy season (January to April). The combined
      human blood index exceeded 92% and the P. falciparum sporozoite rate was 4.8%,
      resulting in estimated inoculation rates of 183 infective bites/ person per
      annum, or an average rate of ~15 infective bites/person/month. CONCLUSIONS: The
      results demonstrate the importance of An. gambiae s.s., An. arabiensis and An.
      funestus in driving the high levels of malaria transmission in the south of
      Malawi. Sustained and high coverage or roll out of current approaches to malaria
      control (primarily insecticide-treated bed nets and indoor residual house
      spraying) in the area are likely to reduce the observed high malaria transmission
      rate and consequently the incidence of human infections, unless impeded by
      increasing resistance of vectors to insecticides.

PMID- 23171125
TI  - Extragenital bullous lichen sclerosus in a pediatric patient: a case report and
      literature review.
AB  - A 14-year-old girl presented with a 1-year history of a pruritic, bullous lesion
      on her posterior neck. A biopsy revealed bullous lichen sclerosus. Although
      unusual, this bullous variant of lichen sclerosus is well recognized in the adult
      literature, but extragenital bullous and hemorrhagic lesions are rare in
      children. A review of this case and the literature describes the clinical
      features, pathophysiology, and treatment options for this extragenital bullous
      variant in an effort to raise awareness of this rare clinical presentation. 

PMID- 23171126
TI  - Footprints of selection in wild populations of Bicyclus anynana along a
      latitudinal cline.
AB  - One of the major questions in ecology and evolutionary biology is how variation
      in the genome enables species to adapt to divergent environments. Here, we study
      footprints of thermal selection in candidate genes in six wild populations of the
      afrotropical butterfly Bicyclus anynana sampled along a c. 3000 km latitudinal
      cline. We sequenced coding regions of 31 selected genes with known functions in
      metabolism, pigment production, development and heat shock responses. These
      include genes for which we expect a priori a role in thermal adaptation and,
      thus, varying selection pressures along a latitudinal cline, and genes we do not
      expect to vary clinally and can be used as controls. We identified amino acid
      substitution polymorphisms in 13 genes and tested these for clinal variation by
      correlation analysis of allele frequencies with latitude. In addition, we used
      two F(ST) -based outlier methods to identify loci with higher population
      differentiation than expected under neutral evolution, while accounting for
      potentially confounding effects of population structure and demographic history.
      Two metabolic enzymes of the glycolytic pathway, UGP and Treh, showed clinal
      variation. The same loci showed elevated population differentiation and were
      identified as significant outliers. We found no evidence of clines in the
      pigmentation genes, heat shock proteins and developmental genes. However, we
      identified outlier loci in more localized parts of the range in the pigmentation
      genes yellow and black. We discuss that the observed clinal variation and
      elevated population divergence in UGP and Treh may reflect adaptation to a
      geographic thermal gradient.

PMID- 23171127
TI  - Community faecal carriage of extended-spectrum beta-lactamase-producing
      Enterobacteriaceae in French children.
AB  - BACKGROUND: The increasing incidence of community acquired infection due to
      Extended-Spectrum Beta-Lactamase (ESBL) -Producing Enterobacteriaceae represent a
      great concern because there are few therapeutic alternatives. The fecal flora of
      children in the community can represent a reservoir for ESBLs genes which are
      located on highly transmissible plasmids and the spread of these genes among
      bacterial pathogens is concerning. Because intestinal carriage is a key factor in
      the epidemiology of ESBL-producing Enterobacteriaceae, the study of the
      prevalence of these resistant bacteria and risk factors in young children is of
      particular interest. METHODS: We assessed the prevalence and risk factors of
      community-acquired faecal carriage of extended-spectrum-beta-lactamase (ESBL)
      producing Enterobacteriaceae in children aged from 6 to 24 months, by means of
      rectal swabbing in community pediatric practices. Child's lifestyle and risk
      factors for carriage of resistant bacteria were noted. RESULTS: Among the 411
      children enrolled, 4.6% carried ESBL-producing Enterobacteriaceae. CTX-M-1, CTX-M
      15 and CTX-M-14 were the predominant ESBLs. The 18 E. coli isolates were
      genetically heterogeneous. Recent third-generation oral-cephalosporin exposure
      was associated with a higher risk of ESBL carriage (AOR=3.52, 95% CI[1.06-11.66],
      p=0.04). CONCLUSIONS: The carriage rate of ESBL-producing Enterobacteriacae in
      young children in the French community setting is noteworthy, underlining the
      importance of this population as a reservoir. Exposure to third-generation oral
      cephalosporins was associated with a significant risk of ESBL carriage in our
      study. Because of the significant public health implications including the
      treatment of community-acquired urinary tract infections, the spread of organisms
      producing ESBLs in the community merits close monitoring with enhanced efforts
      for surveillance.

PMID- 23171128
TI  - A phase 1 study of prasugrel in patients with sickle cell disease:
      pharmacokinetics and effects on ex vivo platelet reactivity.
AB  - AIMS: Prasugrel is a novel thienopyridine P2Y12 adenosine diphosphate (ADP)
      receptor antagonist that inhibits ADP-mediated platelet activation and
      aggregation. Accordingly, it may be useful in reducing platelet-related ischaemia
      in sickle cell disease (SCD). Exposure to prasugrel's active metabolite (Pras-AM)
      and its antiplatelet activity in SCD have not been investigated. METHODS:
      Thirteen adult patients with SCD and an equal number of matched healthy control
      subjects were studied before and after 12 days of 5.0 or 7.5 mg day(-1) prasugrel
      treatment. Platelet reactivity was assessed by light transmission aggregometry
      (LTA), impedance aggregometry (MEA), VerifyNow(r) P2Y12, vasodilator-stimulated
      phosphoprotein (VASP) phosphorylation and Plateletworks. Exposure to Pras-AM was
      also assessed. RESULTS: At baseline, patients with SCD showed increased platelet
      reactivity vs. healthy control subjects with VerifyNow (408 vs. 323 P2Y12
      reaction units (PRU), respectively, P = 0.003) and MEA (106 vs. 77 area under the
      aggregation curve (AU.min), P = 0.002); lower platelet reactivity index with VASP
      flow cytometry (59 vs. 79% platelet reactivity index (PRI), P = 0.018); and no
      significant differences with LTA, VASP enzyme-linked immunosorbent assay or
      Plateletworks. Relative to baseline, prasugrel significantly reduced platelet
      reactivity by all assays in both populations (all P < 0.05). Prasugrel was well
      tolerated, with no bleeding-related events in patients with SCD. The mean
      concentration-time profiles of Pras-AM were comparable between healthy subjects
      and patients with SCD following a single 10 mg prasugrel dose and following the
      12th dose of 7.5 or 5 mg prasugrel. CONCLUSIONS: Results demonstrate that in
      response to prasugrel, patients with SCD and healthy subjects have similar
      degrees of platelet inhibition and exposure to Pras-AM, and provide a basis for
      further study of prasugrel in patients with SCD.

PMID- 23171129
TI  - The RNA processing enzyme polynucleotide phosphorylase negatively controls
      biofilm formation by repressing poly-N-acetylglucosamine (PNAG) production in
      Escherichia coli C.
AB  - BACKGROUND: Transition from planktonic cells to biofilm is mediated by production
      of adhesion factors, such as extracellular polysaccharides (EPS), and modulated
      by complex regulatory networks that, in addition to controlling production of
      adhesion factors, redirect bacterial cell metabolism to the biofilm mode.
      RESULTS: Deletion of the pnp gene, encoding polynucleotide phosphorylase, an RNA
      processing enzyme and a component of the RNA degradosome, results in increased
      biofilm formation in Escherichia coli. This effect is particularly pronounced in
      the E. coli strain C-1a, in which deletion of the pnp gene leads to strong cell
      aggregation in liquid medium. Cell aggregation is dependent on the EPS poly-N
      acetylglucosamine (PNAG), thus suggesting negative regulation of the PNAG
      biosynthetic operon pgaABCD by PNPase. Indeed, pgaABCD transcript levels are
      higher in the pnp mutant. Negative control of pgaABCD expression by PNPase takes
      place at mRNA stability level and involves the 5'-untranslated region of the
      pgaABCD transcript, which serves as a cis-element regulating pgaABCD transcript
      stability and translatability. CONCLUSIONS: Our results demonstrate that PNPase
      is necessary to maintain bacterial cells in the planktonic mode through down
      regulation of pgaABCD expression and PNAG production.

PMID- 23171130
TI  - Microwave absorption properties of carbon nanocoils coated with highly controlled
      magnetic materials by atomic layer deposition.
AB  - In this work, atomic layer deposition is applied to coat carbon nanocoils with
      magnetic Fe(3)O(4) or Ni. The coatings have a uniform and highly controlled
      thickness. The coated nanocoils with coaxial multilayer nanostructures exhibit
      remarkably improved microwave absorption properties compared to the pristine
      carbon nanocoils. The enhanced absorption ability arises from the efficient
      complementarity between complex permittivity and permeability, chiral morphology,
      and multilayer structure of the products. This method can be extended to exploit
      other composite materials benefiting from its convenient control of the impedance
      matching and combination of dielectric-magnetic multiple loss mechanisms for
      microwave absorption applications.

PMID- 23171131
TI  - Tswanarising global gayness: the 'unAfrican' argument, Western gay media imagery,
      local responses and gay culture in Botswana.
AB  - This paper is a strategic intervention in the debate over the value of globalised
      gay identity for emerging sexual minority communities in the South. Focusing on
      self-identifying gay men in Botswana using semi-structured interviews, it
      explores their views of what characterises 'modern gay culture' and relates these
      to international media cliches of a glamorous, stylish, hedonistic gayness. I
      argue that identifying with what is so visibly a Western image of gayness exposes
      sexual minority communities to the most dangerous of the justifications for
      homophobia in Africa, the argument that sexual dissidence is a neo-colonial
      conspiracy to subvert 'African values'. The 'unAfrican' argument has to be taken
      very seriously, not only because it taps into the intense, conflicted emotions at
      the heart of the post-colonial condition, but also because it contains an
      undeniable germ of truth. This poses a dilemma, since global gay discourses,
      including the media cliches, are an important source of inspiration for African
      sexual minorities. A communication activism strategy is proposed to undermine the
      unAfrican argument by cultivating and asserting the 'tswanarisation' of gay
      culture in Botswana that is already taking place. A similar strategy may also be
      effective in other African societies. 

PMID- 23171132
TI  - Ultrasound of the lateral femoral cutaneous nerve in asymptomatic adults.
AB  - BACKGROUND: To define the sites where the lateral femoral cutaneous nerve (LFCN)
      is more easily visualized and to describe the anatomical variations of the LFCN.
      METHODS: A total of 240 LFCNs in 120 volunteers were evaluated with 18 MHz
      ultrasound; the intermuscular space between the tensor fasciae latae muscle and
      the sartorius was used as an initial sonographic landmark. The time taken to
      identify the nerve was recorded. The number of nerve branches at the level of the
      inguinal ligament (IL) and the relationship between the LFCN and the IL was
      assessed. The nerve cross-sectional area (CSA) of the LFCN and the distance
      between the LFCN and the anterior superior iliac spine was measured. RESULTS:
      Each nerve was identified using ultrasound in all participants. The mean time for
      identifying the nerve was 7s for unilateral LFCNs. The nerve passed under the IL
      in 198 cases, whereas in 44 cases, it passed through to the IL. The LFCN
      consisted of 1-4 branches just after its passage under or through the IL. The CSA
      of the LFCN was 1.04 +/- 0.44 mm(2), and the mean distance between the LFCN and
      the anterior superior iliac spine was 15.6 +/- 4.2 mm. CONCLUSIONS: It is easier
      to identify the LFCN if the intermuscular space between the tensor fasciae latae
      muscle and the sartorius is used as an initial sonographic landmark. The
      anatomical variation of the LFCN can be viewed with high-frequency ultrasound.

PMID- 23171133
TI  - Erectile dysfunction and epilepsy: what is the link?

PMID- 23171134
TI  - Aqueous CO2 reduction at very low overpotential on oxide-derived Au
      nanoparticles.
AB  - Carbon dioxide reduction is an essential component of many prospective
      technologies for the renewable synthesis of carbon-containing fuels. Known
      catalysts for this reaction generally suffer from low energetic efficiency, poor
      product selectivity, and rapid deactivation. We show that the reduction of thick
      Au oxide films results in the formation of Au nanoparticles ("oxide-derived Au")
      that exhibit highly selective CO(2) reduction to CO in water at overpotentials as
      low as 140 mV and retain their activity for at least 8 h. Under identical
      conditions, polycrystalline Au electrodes and several other nanostructured Au
      electrodes prepared via alternative methods require at least 200 mV of additional
      overpotential to attain comparable CO(2) reduction activity and rapidly lose
      their activity. Electrokinetic studies indicate that the improved catalysis is
      linked to dramatically increased stabilization of the CO(2)(*-) intermediate on
      the surfaces of the oxide-derived Au electrodes.

PMID- 23171136
TI  - On-chip inductors with self-rolled-up SiNx nanomembrane tubes: a novel design
      platform for extreme miniaturization.
AB  - Inductors are essential components of radio frequency integrated circuits
      (RFICs). While the active devices in RF systems downscale steadily, inductors
      have not been able to keep up with the pace of continual miniaturization because
      of the trade-off between size and performance as well as fabrication complexity.
      Strain-induced self-rolled-up nanotechnology allows the formation of three
      dimensional (3D) architectures, such as multiple-turn spiral tubes, through
      planar processing. Here, we report on using 3D SiN(x) tubular structures with
      accompanying prepatterned metal layers, as a novel on-chip tube inductor design
      platform. We found, by an equivalent lumped circuit and electromagnetic modeling,
      that the 3D metal spiral structure has the ability to significantly better
      confine magnetic field compared to conventional planar spiral on-chip inductors.
      More than 100* reduction in footprint can be realized using this platform while
      achieving excellent electrical performance, including large inductance, high
      quality (Q) factor, and high self-resonance frequency (f(0)).

PMID- 23171135
TI  - PTEN genomic deletion predicts prostate cancer recurrence and is associated with
      low AR expression and transcriptional activity.
AB  - BACKGROUND: Prostate cancer (PCa), a leading cause of cancer death in North
      American men, displays a broad range of clinical outcome from relatively indolent
      to lethal metastatic disease. Several genomic alterations have been identified in
      PCa which may serve as predictors of progression. PTEN, (10q23.3), is a negative
      regulator of the phosphatidylinositol 3-kinase (PIK3)/AKT survival pathway and a
      tumor suppressor frequently deleted in PCa. The androgen receptor (AR) signalling
      pathway is known to play an important role in PCa and its blockade constitutes a
      commonly used treatment modality. In this study, we assessed the deletion status
      of PTEN along with AR expression levels in 43 primary PCa specimens with clinical
      follow-up. METHODS: Fluorescence In Situ Hybridization (FISH) was done on
      formalin fixed paraffin embedded (FFPE) PCa samples to examine the deletion
      status of PTEN. AR expression levels were determined using immunohistochemistry
      (IHC). RESULTS: Using FISH, we found 18 cases of PTEN deletion. Kaplan-Meier
      analysis showed an association with disease recurrence (P=0.03). Concurrently,
      IHC staining for AR found significantly lower levels of AR expression within
      those tumors deleted for PTEN (P<0.05). To validate these observations we
      interrogated a copy number alteration and gene expression profiling dataset of 64
      PCa samples, 17 of which were PTEN deleted. We confirmed the predictive value of
      PTEN deletion in disease recurrence (P=0.03). PTEN deletion was also linked to
      diminished expression of PTEN (P<0.01) and AR (P=0.02). Furthermore, gene set
      enrichment analysis revealed a diminished expression of genes downstream of AR
      signalling in PTEN deleted tumors. CONCLUSIONS: Altogether, our data suggest that
      PTEN deleted tumors expressing low levels of AR may represent a worse prognostic
      subset of PCa establishing a challenge for therapeutic management.

PMID- 23171137
TI  - Metabolomics and mass isotopomer analysis as a strategy for pathway discovery:
      pyrrolyl and cyclopentenyl derivatives of the pro-drug of abuse, levulinate.
AB  - We recently reported that levulinate (4-ketopentanoate) is converted in the liver
      to 4-hydroxypentanoate, a drug of abuse, and that the formation of 4
      hydroxypentanoate is stimulated by ethanol oxidation. We also identified 3
      parallel beta-oxidation pathways by which levulinate and 4-hydroxypentanoate are
      catabolized to propionyl-CoA and acetyl-CoA. We now report that levulinate forms
      three seven-carbon cyclical CoA esters by processes starting with the elongation
      of levulinyl-CoA by acetyl-CoA to 3,6-diketoheptanoyl-CoA. The latter gamma
      diketo CoA ester undergoes two parallel cyclization processes. One process yields
      a mixture of tautomers, i.e., cyclopentenyl- and cyclopentadienyl-acyl-CoAs. The
      second cyclization process yields a methyl-pyrrolyl-acetyl-CoA containing a
      nitrogen atom derived from the epsilon-nitrogen of lysine but without carbons
      from lysine. The cyclic CoA esters were identified in rat livers perfused with
      levulinate and in livers and brains from rats gavaged with calcium levulinate +/-
      ethanol. Lastly, 3,6-diketoheptanoyl-CoA, like 2,5-diketohexane, pyrrolates free
      lysine and, presumably, lysine residues from proteins. This may represent a new
      pathway for protein pyrrolation. The cyclic CoA esters and related pyrrolation
      processes may play a role in the toxic effects of 4-hydroxypentanoate.

PMID- 23171138
TI  - Subchondral osteopenia and accelerated bone remodelling post-ovariectomy - a
      possible mechanism for subchondral microfractures in the aetiology of spontaneous
      osteonecrosis of the knee?
AB  - Osteopenia and subchondral microfractures are implicated in the aetiology of
      spontaneous osteonecrosis of the knee (SPONK). The ovine tibia shows significant
      alterations of the trabecular architecture within the subchondral bone of the
      medial tibial plateau post-ovariectomy (OVX), including reduced trabecular bone
      volume fraction. We hypothesise that accelerated subchondral bone resorption may
      also play a role in increasing microfracture risk at this site. Twenty-two sheep
      were examined in this study; 10 of the sheep underwent OVX, while the remainder
      (n = 13) were kept as controls (CON). Five fluorochrome dyes were administered
      intravenously at 12-week intervals via the jugular vein to both groups, to label
      sites of bone turnover. These animals were then killed at 12 months post
      operatively. Bone turnover was significantly increased in the OVX group in both
      trabecular bone (2.024 vs. 1.047 no. mm(-2) ; P = 0.05) and within the
      subchondral bone plate (4.68 vs. 0.69 no. mm(-2) ; P < 0.001). In addition to the
      classically described turnover visible along trabecular surfaces, we also found
      visual evidence of intra-trabecular osteonal remodelling. In conclusion, this
      study shows significant alterations in bone turnover in both trabecular bone and
      within the subchondral bone plate at 1 year post-OVX. Remodelling of trabecular
      bone was due to both classically described hemi-osteonal and intra-trabecular
      osteonal remodelling. The presence of both localised osteopenia and accelerated
      bone remodelling within the medial tibial plateau provide a possible mechanism
      for subchondral microfractures in the aetiology of SPONK. Further utilisation of
      the OVX ewe may be useful for further study in this field.

PMID- 23171139
TI  - A simple procedure for the comparison of covariance matrices.
AB  - BACKGROUND: Comparing the covariation patterns of populations or species is a
      basic step in the evolutionary analysis of quantitative traits. Here I propose a
      new, simple method to make this comparison in two population samples that is
      based on comparing the variance explained in each sample by the eigenvectors of
      its own covariance matrix with that explained by the covariance matrix
      eigenvectors of the other sample. The rationale of this procedure is that the
      matrix eigenvectors of two similar samples would explain similar amounts of
      variance in the two samples. I use computer simulation and morphological
      covariance matrices from the two morphs in a marine snail hybrid zone to show how
      the proposed procedure can be used to measure the contribution of the matrices
      orientation and shape to the overall differentiation. RESULTS: I show how this
      procedure can detect even modest differences between matrices calculated with
      moderately sized samples, and how it can be used as the basis for more detailed
      analyses of the nature of these differences. CONCLUSIONS: The new procedure
      constitutes a useful resource for the comparison of covariance matrices. It could
      fill the gap between procedures resulting in a single, overall measure of
      differentiation, and analytical methods based on multiple model comparison not
      providing such a measure.

PMID- 23171140
TI  - Warm-up before laparoscopic surgery is not essential.
AB  - BACKGROUND: Several recent studies have suggested that warming up prior to
      surgery may improve surgical performance. The purpose of this study was to
      investigate whether warming up prior to laparoscopic surgery improves surgical
      performance or reduces surgery duration. METHODS: Between August 2011 and January
      2012, a randomized controlled trial was conducted to compare two warm-up
      modalities to no warm-up. The study was conducted at a single site, with nine
      surgeons performing 72 laparoscopic cholecystectomies and 37 laparoscopic
      appendicectomies. Prior to surgery, surgeons were randomized to either
      laparoscopic trainer box warm-up, PlayStation 2 warm-up or no warm-up. The
      activity was performed within 30 min of surgery commencing. Patients provided
      informed consent for the surgery to be digitally recorded. Digital videodiscs
      (DVDs) were reviewed by an independent and blinded assessor. Data were collected
      on duration of surgery, level of training and perceived surgical difficulty.
      Surgical performance was graded using a validated scoring system. RESULTS: From
      the 109 operations performed, there were 75 usable DVDs. Overall, there were no
      statistical differences in the demographics of patients and surgeons in the three
      treatment groups, nor in the subset that had useable DVDs. There were no
      statistical differences in the duration of surgery or surgeon's perceived
      surgical difficulty. There was no statistical difference in surgical performance.
      CONCLUSIONS: This study suggests that warm-up prior to laparoscopic
      cholecystectomy or appendicectomy is not essential, acknowledging that there are
      several study limitations that preclude definitive conclusion.

PMID- 23171141
TI  - Positive association between rs10918859 of the NOS1AP gene and coronary heart
      disease in male Han Chinese.
AB  - Westaway et al. have revealed a significant association between common variants
      of calsequestrin-2 (CASQ2) and nitric oxide synthase 1 (neuronal) adaptor protein
      (NOS1AP) and the risk of sudden death in patients of coronary heart disease
      (CHD). In light of the findings, we aim to explore the association between
      variants of the two genes and CHD risk in Han Chinese. Our results show a
      significant contribution of rs10918859 of the NOS1AP gene to CHD in Han Chinese
      (genotype: chi(2)=8.33, df=2, p=0.015; allele: chi(2)=4.00, df=1, p=0.047, odds
      ratio [OR]=1.44, 95% confidence interval [CI]=1.00-2.05). The association of
      rs10918859 with CHD is seen only in men (genotype: chi(2)=7.81, df=2, p=0.02;
      allele: chi(2)=4.49, df=1, p=0.03, OR=1.66, 95% CI=1.03-2.66). Moreover,
      rs10918859 is likely to exert its effect under a dominant model in men
      (chi(2)=7.6, df=1, p=0.005, OR=2.46, 95% CI=1.29-4.71). No association is
      observed between CASQ2 variants and CHD risk. The frequencies of rs12084280-C and
      rs10918859-A are higher in Han Chinese (36.7% and 41.6%) than those in Europeans
      (11% and 19.4%, respectively). These ethnic differences imply that further
      validation of NOS1AP in the susceptibility of CHD in other populations is
      warranted. We confirm that rs10918859 of the NOS1AP gene is associated with CHD
      in Han Chinese. In addition, here we report a gender effect in the association
      between rs10918859 of the NOS1AP gene and CHD.

PMID- 23171142
TI  - Aberrant apolipoprotein E expression and cognitive dysfunction in patients with
      poststroke depression.
AB  - BACKGROUND: Apolipoprotein E (ApoE) is associated with some diseases with
      cognitive function defect. AIMS: The purpose of this study was to examine the
      influence of ApoE on poststroke depression (PSD) risk and to define objective
      markers for diagnosis. METHODS: The cognitive function, serum ApoE, and
      peripheral mononuclear blood cell ApoE mRNA expression of patients with PSD were
      compared to age-matched control patients with stroke and healthy volunteers.
      Sixty-seven patients with stroke were selected according to the cerebral
      infarction diagnosis standard of the Fourth National Cerebrovascular Disease
      Conference and divided into a PSD group (28 patients, 43-76 years old) or a
      control stroke group (39 patients, 43-78 years old) using the Hamilton Rating
      Scale for Depression, and compared to 40 healthy volunteers (42-78 years old).
      Cognitive function was evaluated by analysis of event-related potentials (ERPs),
      while expression of ApoE mRNA was determined by quantitative reverse
      transcription-polymerase chain reaction and serum ApoE by ELISA. RESULTS: The
      latencies of ERP components N2 and P3 were prolonged, and the P3 amplitude was
      lower in the PSD group compared to the control stroke group and healthy controls
      (p<0.01). There were no significant group differences in N1 and P2 latencies (all
      p>0.05). The latency of N2 was positively correlated to the P3 latency in the PSD
      group (p<0.05). No associations were detected between P3 amplitude, expression of
      ApoE mRNA, and serum ApoE in the PSD group (all p>0.05). The ERP results
      indicated that patients with PSD were significantly slower at identifying a
      target stimulus, suggesting deficits in perception and/or cognitive processing.
      Peripheral expression of ApoE mRNA was lower in the PSD group than the control
      stroke group (p<0.701) while serum ApoE was higher than in the control stroke
      group (p<0.05), possibly reflecting a feedback reduction in expression.
      CONCLUSION: We suggest that aberrant serum ApoE together with abnormalities in
      some ERP components may be useful markers for assessment of PSD risk and clinical
      diagnosis.

PMID- 23171143
TI  - Association of paraoxonase1 gene Q192R polymorphism and apolipoprotein B in Asian
      Indian women with coronary artery disease risk.
AB  - BACKGROUND/AIMS: Human serum paraoxonase1 (PON1), a high-density lipoprotein
      associated enzyme, prevents oxidative modification of low-density lipoprotein
      and, thus, arrests the development of atheroma formation, whose major consequence
      is the development of coronary artery disease (CAD). A single-nucleotide
      polymorphism (SNP) Q192R in the coding region at pon1 locus is a determinant of
      PON1 activity. The relationship between PON1 activity and vascular disease may be
      influenced by the relationship of PON1 activity or PON1 SNP genotype to lipid and
      apolipoprotein (Apo) levels. The aim of the study is to ascertain the prevalence
      of PON1 Q192R polymorphism in male and female subjects with and without CAD along
      with its influence on ApoA-I and ApoB levels in Asian Indians. METHODS:
      Determination of genotypes was carried out in 249 diagnosed CAD cases and in 243
      age-, gender-matched asymptomatic controls by polymerase chain reaction
      restriction fragment length polymorphism. Fasting plasma Apo-levels were
      estimated by immunoturbidimetric assay. RESULTS: The genotype frequencies did not
      differ markedly between the overall CAD and control groups and in male and female
      subjects, suggesting a lack of any genotype-CAD correlation. ApoB levels were
      found to be higher in female patients carrying RR when compared with QQ genotypes
      (p=0.03) with no effect on controls. This may be attributed to the postmenopausal
      state of the women. CONCLUSION: PON1 Q192R can be used as the DNA marker test to
      evaluate the risk of CAD in postmenopausal Indian women with high ApoB.

PMID- 23171144
TI  - Child health nurses in the Solomon Islands: lessons for the Pacific and other
      developing countries.
AB  - OBJECTIVES: To understand the roles of nurses with advanced training in
      paediatrics in the Solomon Islands, and the importance of these roles to child
      health. To understand how adequately equipped child health nurses feel for these
      roles, to identify the training needs, difficulties and future opportunities.
      DESIGN: Semi-structured interviews. SETTINGS: Tertiary hospital, district
      hospitals and health clinics in the Solomon Islands. PARTICIPANTS: Twenty-one
      paediatric nurses were interviewed out of a total of 27 in the country. RESULTS:
      All nurses were currently employed in teaching, clinical or management areas. At
      least one or two nurses were working in each of 7 of the 9 provinces; in the two
      smaller provinces there were none. Many nurses were sole practitioners in remote
      locations without back-up from doctors or other experienced nurses; all had
      additional administrative or public health duties. Different types of courses
      were identified: a residential diploma through the University of Papua New Guinea
      or New Zealand and a diploma by correspondence through the University of Sydney.
      CONCLUSIONS: Child health nurses in the Solomon Islands fulfill vital clinical,
      public health, teaching and administrative roles. Currently they are too few in
      number, and this is a limiting factor for improving the quality of child health
      services in that country. Current methods of training require overseas travel, or
      are expensive, or lack relevance, or remove nurses from their work-places and
      families for prolonged periods of time. A local post-basic child health nursing
      course is urgently needed, and models exist to achieve this.

PMID- 23171145
TI  - Cross-cultural adaptation and validation of the profile of chronic pain: screen
      for a Brazilian population.
AB  - OBJECTIVE: To translate the original English version of the Profile of Chronic
      Pain: Screen (PCP:S) into Brazilian Portuguese and examine basic psychometric
      properties of the translated version. We investigated ceiling and floor effects,
      internal consistency, factor structure, convergent validity, and the ability of
      the Brazilian PCP:S (B-PCP:S) to discriminate persons with pain who were either
      employed or not working, or in treatment or not in treatment. METHODS: The
      Brazilian Portuguese version of the Profile of Chronic Pain: Screen (B-PCP:S) was
      administered to a sample of 414 adults (men = 67). Pain catastrophizing was also
      assessed. Subsamples with special conditions (working despite pain [N = 116] vs
      not working due to pain [N = 122], and not receiving treatment for pain [N = 119]
      vs receiving treatment [N = 119]) were identified to investigate the
      discriminative properties of B-PCP:S. RESULTS: For the B-PCP:S, Cronbach's alpha
      values were 0.76 (severity), 0.88 (interference), and 0.87 (emotional burden).
      Confirmatory factor analysis supported the original, English language three
      factor structure, with the comparative fit index = 0.93, root mean square error
      of approximation = 0.075, and normed fit index = 0.93. Significant correlations
      were found between pain intensity, pain interference, and emotional burden, and a
      criterion measure of catastrophizing (correlation coefficients ranged from 0.48
      to 0.66, P < 0.01). B-PCP:S scores (severity, interference, and emotional burden)
      were higher in subjects under a doctor's care for pain and in those not working
      due to pain. CONCLUSION: This B-PCP:S version was found to be a reliable
      instrument, with basic evidence of validity for the evaluation of pain severity,
      interference, and emotional burden in Brazilian Portuguese adults. The profile of
      B-PCP:S scores was similar to that observed in the original version.

PMID- 23171146
TI  - Atypical features of a midline pre-pontine epidermoid cyst.
AB  - Intracranial epidermoid cysts are uncommon lesions with typical radiological and
      operative findings. We report a midline cystic lesion in the pre-pontine cistern,
      with radiological features of an epidermoid, but intra-operatively yielding a
      thin-walled cyst with fluid contents. The cyst wall showed stratified squamous
      epithelium on histopathology.

PMID- 23171147
TI  - Oesophageal naso-pharyngeal catheter use for airway management in patients for
      awake craniotomy.
AB  - In asleep-awake-asleep anaesthesia, removal and reinsertion of endotracheal tubes
      are associated with significant difficulty and risk. To overcome this, an
      oesophageal naso-pharyngeal catheter was developed. Its sealed distal end is
      placed in the oesophagus via the nose and the proximal end is connected to a
      ventilator or breathing circuit. For anaesthesia, the distal end balloon is
      inflated to seal the oesophagus and the larger proximal balloon is inflated to
      seal the naso- and oro-pharyngeal cavities. Ventilation occurs via the side holes
      on the tube located between the balloons and which sit over the laryngeal inlet.
      This eliminates the need to remove and reestablish airway devices with the
      associated risks. The authors report the preliminary experience using this device
      in 17 patients who underwent awake craniotomy for surgery adjacent to the
      'eloquent' areas.

PMID- 23171148
TI  - The incidence of infection for adults undergoing supra-tentorial craniotomy for
      tumours without hair removal.
AB  - AIMS & OBJECTIVES: The aim of the study was to look at the infection rate in
      adults undergoing craniotomies without hair removal and compare the results with
      the usual practice of pre-operative shaving/clipping. MATERIALS & METHODS: One
      hundred consecutive adult patients who had elective supra-tentorial craniotomy
      for tumour were studied prospectively. A uniform policy of performing surgery
      without hair removal was adopted. Patients were followed up prospectively to look
      for surgical site infection. The rate of infection was determined and the results
      were compared with the published data on similar procedures where hair removal
      was carried out before surgery. RESULTS: A total of three patients developed
      surgical-site infection. One infection occurred in the glioma and two in the
      meningioma subgroup. The rate of infection is comparable to the published figures
      where pre-operative hair removal was performed routinely. CONCLUSIONS: Cranial
      surgery with hair left in place does not pre-dispose to an increased infection
      risk for adults undergoing tumour surgery.

PMID- 23171149
TI  - Hemi-chorea: an unusual presentation of brainstem glioma.
AB  - Brainstem gliomas are neoplasms primarily affecting children. Depending on the
      type, they usually present with varying combination of multiple bilateral or
      unilateral cranial nerve palsies, long-tract signs, ataxia and sometimes
      hydrocephalus. Though movement disorders have been reported in association with
      basal ganglia and thalamic tumours, hemi-chorea, as a presentation of brainstem
      glioma, has not been reported till date. I present a case of a 9-year-old female
      child, who presented with complaints of difficulty in walking and involuntary
      movements affecting the left upper and lower limb. On examination, she had chorea
      involving left side of the body, bilateral lateral rectus palsy, with spasticity
      of right upper and lower limb. CT scan and MRI of the brain showed focal glioma
      involving the upper pons and midbrain. The patient underwent surgery in the form
      of sub-occipital craniotomy and tumour removal. Postoperative imaging studies
      showed no residual tumour. Histopathological examination was suggestive of
      pilocytic astrocytoma grade 1. Postoperatively hemi-chorea decreased in
      intensity, but did not disappear completely.

PMID- 23171150
TI  - An exploratory GIS-based method to identify and characterise landscapes with an
      elevated epidemiological risk of Rhodesian human African trypanosomiasis.
AB  - BACKGROUND: Specific land cover types and activities have been correlated with
      Trypanosoma brucei rhodesiense distributions, indicating the importance of
      landscape for epidemiological risk. However, methods proposed to identify
      specific areas with elevated epidemiological risk (i.e. where transmission is
      more likely to occur) tend to be costly and time consuming. This paper proposes
      an exploratory spatial analysis using geo-referenced human African
      trypanosomiasis (HAT) cases and matched controls from Serere hospital, Uganda
      (December 1998 to November 2002) to identify areas with an elevated
      epidemiological risk of HAT. METHODS: Buffers 3 km from each case and control
      were used to represent areas in which village inhabitants would carry out their
      daily activities. It was hypothesised that the selection of areas where several
      case village buffers overlapped would enable the identification of locations with
      increased risk of HAT transmission, as these areas were more likely to be
      frequented by HAT cases in several surrounding villages. The landscape within
      these overlap areas should more closely relate to the environment in which
      transmission occurs as opposed to using the full buffer areas. The analysis was
      carried out for each of four annual periods, for both cases and controls, using a
      series of threshold values (number of overlapping buffers), including a threshold
      of one, which represented the benchmark (e.g. use of the full buffer area as
      opposed to the overlap areas). RESULTS: A greater proportion of the overlap areas
      for cases consisted of seasonally flooding grassland and lake fringe swamp, than
      the control overlap areas, correlating well with the preferred habitat of the
      predominant tsetse species within the study area (Glossina fuscipes fuscipes).
      The use of overlap areas also resulted in a greater difference between case and
      control landscapes, when compared with the benchmark (using the full buffer
      area). CONCLUSIONS: These results indicate that the overlap analysis has enabled
      the selection of areas more likely to represent epidemiological risk zones than
      similar analyses using full buffer areas. The identification of potential
      epidemiological risk zones using this method requires fewer data than other
      proposed methods and further development may provide vital information for the
      targeting of control measures.

PMID- 23171152
TI  - Melatonin, melatonin isomers and stilbenes in Italian traditional grape products
      and their antiradical capacity.
AB  - Although polyphenols represent the paradigm of the health-promoting effects
      ascribed to grape products, recently, attention has been paid to dietary
      melatonin, significantly present in Mediterranean foods. In this work, we
      measured melatonin, its isomers, stilbenes (trans- and cis-resveratrol and their
      glucosides, piceids) and total polyphenols in some different grape products (red,
      white and dessert wines, grape juices and Modena balsamic vinegars) of distinct
      Italian areas. We also evaluated their antiradical activity by DPPH(.) and
      ABTS(.+) assays. For indoleamine analysis, the separation was carried out on a
      1.7-MUm C18 BEH column and the detection performed by means of mass spectrometry
      with electrospray ionization in positive ion mode with multiple reaction
      monitoring. The confirmation of the peak identity was accomplished by injection
      into the high-resolution system (Orbitrap) using accurate mass measurements
      (error below 1.0 ppm). Mass spectrometry analyses revealed, for the first time,
      the presence of melatonin in dessert wines and balsamic vinegars, as well as the
      occurrence of three different melatonin isomers in grape products.

PMID- 23171151
TI  - Neuropsychological, behavioral, and anatomical evolution in right temporal
      variant frontotemporal dementia: a longitudinal and post-mortem single case
      analysis.
AB  - We describe a patient with semantic variant of frontotemporal dementia who
      received longitudinal clinical evaluations and structural MRI scans and
      subsequently came to autopsy. She presented with early behavior changes and
      semantic loss for foods and people and ultimately developed a pervasive semantic
      impairment affecting social-emotional as well as linguistic domains. Imaging
      revealed predominant atrophy of the right temporal lobe, with later involvement
      of the left, and pathology confirmed bilateral temporal involvement. Findings
      support the view that left and right anterior temporal lobes serve as semantic
      hubs that may be affected differentially in semantic variant by early, relatively
      unilateral damage. 

PMID- 23171153
TI  - Impact of baseline HIV-1 RNA levels on initial highly active antiretroviral
      therapy outcome: a meta-analysis of 12,370 patients in 21 clinical trials*.
AB  - BACKGROUND: Individual randomized trials of first-line antiretroviral treatment
      do not consistently show an association between higher baseline HIV-1 RNA and
      lower efficacy. METHODS: A MEDLINE search identified 21 HIV clinical trials with
      published analyses of antiretroviral efficacy by baseline HIV-1 RNA, using a
      standardized efficacy endpoint of HIV-1 RNA suppression <50 copies/mL at week 48.
      RESULTS: Among 21 clinical trials identified, eight evaluated only nonnucleoside
      reverse transcriptase inhibitor (NNRTI)-based combinations, eight evaluated only
      protease inhibitor-based regimens and five compared different treatment classes.
      Ten of the trials included tenofovir (TDF)/emtricitabine (FTC) as only nucleoside
      reverse transcriptase inhibitor (NRTI) backbone, in addition but not restricted
      to abacavir (ABC)/lamivudine (3TC) (n = 7), zidovudine (ZDV)/3TC (n = 4) and
      stavudine (d4T)/3TC (n = 1). Across trials, the mean percentage of patients
      achieving HIV-1 RNA < 50 copies/mL at week 48 was 81.5% (5322 of 6814) for
      patients with baseline HIV-1 RNA < 100 000, vs. 72.6% (3949 of 5556) for patients
      with HIV-1 RNA > 100 000 copies/mL. In the meta-analysis, the absolute difference
      in efficacy between low and high HIV-1 RNA subgroups was 7.4% [95% confidence
      interval (CI) 5.9-8.9%; P < 0.001]. This difference was consistent in trials of
      NNRTI-based treatments (difference = 6.9%; 95% CI 4.3-9.6%), protease inhibitor
      based treatments (difference = 8.4%; 95% CI 6.0-10.8%) and integrase or chemokine
      (C-C motif) receptor 5 (CCR5)-based treatments (difference = 6.0%; 95% CI 2.1
      9.9%) and for trials using TDF/FTC (difference = 8.4%; 95% CI 6.0-10.8%); there
      was no evidence for heterogeneity of this difference between trials (Cochran's Q
      test; not significant). CONCLUSIONS: In this meta-analysis of 21 first-line
      clinical trials, rates of HIV-1 RNA suppression at week 48 were significantly
      lower for patients w ith baseline HIV-1 RNA > 100 000 copies/mL (P < 0.001). This
      difference in efficacy was consistent across trials of different treatment
      classes and NRTI backbones.

PMID- 23171155
TI  - Clear cell acanthoma.
AB  - Clear cell acanthoma (CCA), is an asymptomatic benign lesion of unknown origin
      and aetiology, which typically presents as a red to brown, dome-shaped papule on
      the leg. We discuss the case of a patient with an irregular plaque of
      hypopigmented papules whose diagnosis of CCA was only made by biopsy, and review
      the characteristic presentation, uncommon variants, locations and associated
      conditions of this lesion. The diagnosis is based on histopathology and/or
      immunohistochemistry, but the variable clinical presentation may make diagnosis
      difficult. The differential diagnosis includes skin tumours and inflammatory and
      pigmentary dermatoses. The lesions do not regress spontaneously, and excisional
      removal is the preferred treatment.

PMID- 23171154
TI  - Resistance profiles of urinary tract infections in general practice--an
      observational study.
AB  - BACKGROUND: Guideline recommendations on therapy in urinary tract infections are
      based on antibiotic resistance rates. Due to a lack of surveillance data, little
      is known about resistance rates in uncomplicated urinary tract infection (UTI) in
      general practice in Germany. In a prospective observational study, urine cultures
      of all women presenting with urinary tract infections in general practice were
      analysed. Resistance rates against antibiotics recommended in German guidelines
      on UTI are presented. METHODS: In a prospective, multi-center observational study
      general practitioner included all female patients >= 18 years with clinically
      suspected urinary tract infection. Only patients receiving an antibiotic therapy
      within the last two weeks were excluded. RESULTS: 40 practices recruited 191
      female patients (mean age 52 years; range 18-96) with urinary tract infections.
      Main causative agent was Escherichia coli (79%) followed by Enterococcus faecalis
      (14%) and Klebsiella pneumoniae (7.3%).Susceptibility of E.coli as the main
      causative agent was highest against fosfomycin and nitrofurantoin, with low
      resistance rates of 4,5%; 2,2%. In 17,5%, E.coli was resistant to trimethoprim
      and in 8,5% to ciprofloxacin. CONCLUSIONS: Resistance rates of uropathogens from
      unselected patients in general practice differ from routinely collected
      laboratory data. These results can have an impact on antibiotic prescribing and
      treatment recommendations.

PMID- 23171156
TI  - Excision biopsy in a patient with suspected local anaesthetic allergy: use of
      0.9% saline with benzyl alcohol as local anaesthesia.
AB  - Dermatologists may see patients with actual or suspected local anaesthetic (LA)
      allergy who require an urgent dermatological procedure to be performed without
      time for formal allergy testing. We report a case of shave biopsy and subsequent
      excision biopsy of an atypical naevus performed using tumescent analgesia with
      0.9% saline containing benzyl alcohol preservative. The tumescence itself and the
      benzyl alcohol present in the 0.9% saline solution provided sufficient analgesia
      for excision. This technique may be an option for managing urgent procedures in
      patients suspected or known to have allergy to LA.

PMID- 23171157
TI  - Ocular and cutaneous melanoma: the Glasgow experience.

PMID- 23171158
TI  - Unusual flexural papules in a male patient with diabetes.

PMID- 23171159
TI  - Non-linear relationship between intensity of plant-animal interactions and
      selection strength.
AB  - The shape of the relationship between intensity of biotic interactions and
      strength of selection is important for spatial variation in selection, but is
      little explored. We quantified interactions and selection in 69 populations of
      the short-lived herb Primula farinosa. As predicted because of saturation and
      depletion effects, the strength of selection on a discrete and on a continuously
      varying floral display trait were in several cases significantly non-linearly
      related to the mean intensity of mutualistic and antagonistic interactions.
      Strength of selection was strongest at low levels of fruit initiation and at high
      intensities of seed predation. Seed predation varied more among populations than
      did fruit initiation and could explain a larger proportion of the among
      population variation in strength of selection. Our results support the contention
      that interaction intensity affects selection strength, and suggests that for
      mutualistic and antagonistic interactions that can be saturated or depleted, this
      relationship is sometimes non-linear.

PMID- 23171160
TI  - Community-based organizations in the health sector: a scoping review.
AB  - Community-based organizations are important health system stakeholders as they
      provide numerous, often highly valued programs and services to the members of
      their community. However, community-based organizations are described using
      diverse terminology and concepts from across a range of disciplines. To better
      understand the literature related to community-based organizations in the health
      sector (i.e., those working in health systems or more broadly to address
      population or public health issues), we conducted a scoping review by using an
      iterative process to identify existing literature, conceptually map it, and
      identify gaps and areas for future inquiry.We searched 18 databases and conducted
      citation searches using 15 articles to identify relevant literature. All search
      results were reviewed in duplicate and were included if they addressed the key
      characteristics of community-based organizations or networks of community-based
      organizations. We then coded all included articles based on the country focus,
      type of literature, source of literature, academic discipline, disease sector,
      terminology used to describe organizations and topics discussed. We identified
      186 articles addressing topics related to the key characteristics of community
      based organizations and/or networks of community-based organizations. The
      literature is largely focused on high-income countries and on mental health and
      addictions, HIV/AIDS or general/unspecified populations. A large number of
      different terms have been used in the literature to describe community-based
      organizations and the literature addresses a range of topics about them (mandate,
      structure, revenue sources and type and skills or skill mix of staff), the
      involvement of community members in organizations, how organizations contribute
      to community organizing and development and how they function in networks with
      each other and with government (e.g., in policy networks).Given the range of
      terms used to describe community-based organizations, this scoping review can be
      used to further map their meanings/definitions to develop a more comprehensive
      typology and understanding of community-based organizations. This information can
      be used in further investigations about the ways in which community-based
      organizations can be engaged in health system decision-making and the mechanisms
      available for facilitating or supporting their engagement.

PMID- 23171161
TI  - Fire-adapted Gondwanan Angiosperm floras evolved in the Cretaceous.
AB  - BACKGROUND: Fires have been widespread over the last 250 million years, peaking
      60-125 million years ago (Ma), and might therefore have played a key role in the
      evolution of Angiosperms. Yet it is commonly believed that fireprone communities
      existed only after the global climate became more arid and seasonal 15 Ma. Recent
      molecular-based studies point to much earlier origins of fireprone Angiosperm
      floras in Australia and South Africa (to 60 Ma, Paleocene) but even these were
      constrained by the ages of the clades examined. RESULTS: Using a molecular-dated
      phylogeny for the great Gondwanan family Proteaceae, with a 113-million-year
      evolutionary history, we show that the ancestors of many of its characteristic
      sclerophyll genera, such as Protea, Conospermum, Leucadendron, Petrophile,
      Adenanthos and Leucospermum (all subfamily Proteoideae), occurred in fireprone
      habitats from 88 Ma (83-94, 95% HPD, Mid-Upper Cretaceous). This coincided with
      the highest atmospheric oxygen (combustibility) levels experienced over the past
      150 million years. Migration from non-fireprone (essentially rainforest-climate
      type) environments was accompanied by the evolution of highly speciose clades
      with a range of seed storage traits and fire-cued seed release or germination
      mechanisms that was diagnostic for each clade by 71 Ma, though the ant-dispersed
      lineage (as a soil seed-storage subclade) was delayed until 45 Ma. CONCLUSIONS:
      Focusing on the widespread 113-million-year-old family Proteaceae, fireproneness
      among Gondwanan Angiosperm floras can now be traced back almost 90 million years
      into the fiery Cretaceous. The associated evolution of on-plant (serotiny) and
      soil seed storage, and later ant dispersal, affirms them as ancient adaptations
      to fire among flowering plants.

PMID- 23171162
TI  - Restoration of endodontically treated teeth with major hard tissue loss--bond
      strength of conventionally and adhesively luted fiber-reinforced composite posts.
AB  - AIM: To evaluate the influence of the luting system on the pull-out bond strength
      of conventionally and adhesively luted fiber-reinforced composite posts (FRCPs).
      MATERIAL AND METHODS: One hundred extracted bovine teeth (Di 3) were
      endodontically treated and randomly assigned to nine test groups and one control
      group (n = 10) according to luting system. After preparing the post cavities (8
      mm), the custom-made FRCPs were inserted using conventional glass-ionomer cement
      (Ketac Cem), resin-reinforced glass-ionomer cement (Meron Plus and Fuji Plus),
      self-adhesive resin cement (RelyX Unicem and BisCem), self-conditioning adhesive
      and resin cement [Multilink Primer + Multilink and AdheSE + DC Activator +
      MultiCore Flow, or etch-and-rinse adhesive and resin cement (SealBond Ultima +
      CoreCem, and LuxaBond + LuxaCore Z). As a control, custom-made titanium posts
      were inserted with Ketac Cem. After water storage (37 degrees C, 24 h, dark), the
      pull-out test was performed, followed by failure mode evaluation. The data were
      statistically analyzed (alpha = 0.05) using analysis of variance and the Dunnett
      T3 post hoc test. RESULTS: Luting system type and identity significantly
      influenced bond strength (P < 0.001); the bond strengths of all luting systems
      except Ketac Cem, MeronPlus, and BisCem were significantly higher than the
      control (4.4 +/- 1.1 MPa). RelyX Unicem (12.0 +/- 3.0 MPa) and LB + LCZ (14.8 +/-
      2.3 MPa) generated the highest bond strengths. The clinical application was
      demonstrated by restoring a traumatized tooth with extensive coronal destruction
      and thin root canal walls, using a FRCP combined with direct composite build-up.
      CONCLUSION: Luting system selection significantly influenced the bond strength of
      conventionally and adhesively luted FRCPs to bovine root canal dentin.

PMID- 23171163
TI  - The evolution of north-east Atlantic gadfly petrels using statistical
      phylogeography.
AB  - Macaronesia (north-east Atlantic archipelagos) has been host to complex patterns
      of colonization and differentiation in many groups of organisms including
      seabirds such as gadfly petrels (genus Pterodroma). Considering the subspecies of
      widely distributed soft-plumaged petrel for many years, the taxonomic status of
      the three gadfly petrel taxa breeding in Macaronesia is not yet settled, some
      authors advocating the presence of three, two or one species. These birds have
      already been the subject of genetic studies with only one mtDNA gene and
      relatively modest sample sizes. In this study, using a total of five genes (two
      mitochondrial genes and three nuclear introns), we investigated the population
      and phylogeographical histories of petrel populations breeding on Madeira and
      Cape Verde archipelagos. Despite confirming complete lineage sorting with mtDNA,
      analyses with nucDNA failed to reveal any population structuring and Isolation
      with Migration analysis revealed the absence of gene flow during the
      differentiation process of these populations. It appears that the three
      populations diverged in the late Pleistocene in the last 150 000 years, that is
      10 times more recently than previous estimates based solely on one mtDNA gene.
      Finally, our results suggest that the Madeira petrel population is ancestral
      rather than that from Cape Verde. This study strongly advocates the use of
      nuclear loci in addition to mtDNA in demographical and phylogeographical history
      studies.

PMID- 23171164
TI  - Prevalence of germline BAP1 mutation in a population-based sample of uveal
      melanoma cases.

PMID- 23171165
TI  - Ecologically relevant choanoflagellates collected from hypoxic water masses of
      the Baltic Sea have untypical mitochondrial cristae.
AB  - BACKGROUND: Protist communities inhabiting oxygen depleted waters have so far
      been characterized through both microscopical observations and sequence based
      techniques. However, the lack of cultures for abundant taxa severely hampers our
      knowledge on the morphology, ecology and energy metabolism of hypoxic protists.
      Cultivation of such protists has been unsuccessful in most cases, and has never
      yet succeeded for choanoflagellates, even though these small bacterivorous
      flagellates are known to be ecologically relevant components of aquatic protist
      communities. RESULTS: Quantitative data for choanoflagellates and the vertical
      distribution of Codosiga spp. at Gotland and Landsort Deep (Baltic Sea) indicate
      its preference for oxygen-depleted zones. Strains isolated and cultivated from
      these habitats revealed ultrastructural peculiarities such as mitochondria
      showing tubular cristae never seen before for choanoflagellates, and the first
      observation of intracellular prokaryotes in choanoflagellates. Analysis of their
      partial 28S rRNA gene sequence complements the description of two new species,
      Codosiga minima n. sp. and C. balthica n. sp. These are closely related with but
      well separated from C. gracilis (C. balthica and C. minima p-distance to C.
      gracilis 4.8% and 11.6%, respectively). In phylogenetic analyses the 18S rRNA
      gene sequences branch off together with environmental sequences from hypoxic
      habitats resulting in a wide cluster of hypoxic Codosiga relatives so far only
      known from environmental sequencing approaches. CONCLUSIONS: Here, we establish
      the morphological and ultrastructural identity of an environmental
      choanoflagellate lineage. Data from microscopical observations, supplemented by
      findings from previous culture-independent methods, indicate that C. balthica is
      likely an ecologically relevant player of Baltic Sea hypoxic waters. The
      possession of derived mitochondria could be an adaptation to life in hypoxic
      environments periodically influenced by small-scale mixing events and changing
      oxygen content allowing the reduction of oxygen consuming components. In view of
      the intricacy of isolating and cultivating choanoflagellates, the two new
      cultured species represent an important advance to the understanding of the
      ecology of this group, and mechanisms of adaptations to hypoxia in protists in
      general.

PMID- 23171166
TI  - Protocol for a randomised controlled trial to estimate the effects and costs of a
      patient centred educational intervention in glaucoma management.
AB  - BACKGROUND: Poor glaucoma education is thought to be a causative factor of non
      adherence to glaucoma therapy. However, the multi-factorial nature of non
      adherent behaviour may explain the failure of purely educational interventions to
      achieve significant improvement in adherence. Behaviour Change Counselling (BCC)
      allows both the imparting of information and assessment of patient ambivalence to
      medication use and may elicit behaviour change in order to achieve better
      adherence. The chronic and complex nature of glaucoma means that patient non
      adherence to glaucoma therapy does not easily correlate with measureable
      objective clinical endpoints. However, electronic medication monitoring offers an
      objective method of measuring adherence without reliance on clinical endpoints.
      METHODS/DESIGN: The study is a randomised controlled trial (RCT) with glaucoma
      (open angle) or ocular hypertension patients attending a glaucoma clinic and
      prescribed travoprost. The study will determine whether additional glaucoma
      education using BCC is beneficial and cost effective in improving adherence with
      glaucoma therapy. An 8-month follow-up period, using an electronic adherence
      monitoring device (Travalert dosing aid, TDA), will indicate if the intervention
      is likely to be sustained in the longer term. Additionally, a cost-effectiveness
      framework will be used to estimate the cost benefit of improving adherence. The
      development of a novel intervention to deliver glaucoma education using BCC
      required practitioner training and fidelity testing. Five practitioners were
      successfully trained to become Glaucoma Support Assistants able to deliver the
      BCC intervention. The research group had prior clinical and investigative
      experience in this setting, and used multiple strategies to design a method to
      address the study objectives. DISCUSSION: This RCT, using BCC to improve
      adherence to ocular hypotensive therapy, to our knowledge is the first within
      this disease area. Using a variety of adherence measures allows examination of
      the known inaccuracies of patient self-report with respect to glaucoma
      medication. The novel BCC component has undergone fidelity testing using BECCI
      and the BCC template will ensure conformity to a standardised intervention. TRIAL
      REGISTRATION: Current Controlled Trials: ISRCTN89683704.

PMID- 23171168
TI  - Mutational analysis of MukE reveals its role in focal subcellular localization of
      MukBEF.
AB  - Bacterial condensin MukBEF is essential for global folding of the Escherichia
      coli chromosome. MukB, a SMC (structural maintenance of chromosome) protein,
      comprises the core of this complex and is responsible for its ATP-modulated DNA
      binding and reshaping activities. MukF serves as a kleisin that modulates MukB
      DNA interactions and links MukBs into macromolecular assemblies. Little is known
      about the function of MukE. Using random mutagenesis, we generated six loss-of
      function point mutations in MukE. The surface mutations clustered in two places.
      One of them was at or close to the interface with MukF while the other was away
      from the known interactions of the protein. All loss-of-function mutations
      affected focal localization of MukBEF in live cells. In vitro, however, only some
      of them interfered with the assembly of MukBEF into a complex or the ability of
      MukEF to disrupt MukB-DNA interactions. Moreover, some MukE mutants were able to
      join intracellular foci formed by endogenous MukBEF and most of the mutants were
      efficiently incorporated into MukBEF even in the presence of endogenous MukE.
      These data reveal that focal localization of MukBEF involves other activities
      besides DNA binding and that MukE plays a central role in them.

PMID- 23171167
TI  - Comparison of mixed and lamellar coculture spatial arrangements for tissue
      engineering capillary networks in vitro.
AB  - Coculture of endothelial cells (ECs) and smooth muscle cells (SMCs) in vitro can
      yield confluent monolayers or EC networks. Factors influencing this transition
      are not known. In this study, we examined whether the spatial arrangement of EC
      SMC cocultures affected EC migration, network morphology, and angiogenic protein
      secretion. Human umbilical cord blood-derived ECs (hCB-ECs) were grown in
      coculture with human aortic SMCs in either a mixed or lamellar spatial geometry
      and analyzed over a culture period of 12 days. The hCB-ECs cultured on SMCs in a
      mixed system had higher cell speeds, shorter persistence times, and lower random
      motility coefficients than ECs in a lamellar system. By day 12 of coculture,
      mixed systems demonstrated greater anastomoses and capillary loop formation than
      lamellar systems as evidenced by a higher number of branch points, angle of
      curvature between branch points, and percentage of imaged area covered by
      networks. The network morphology was more uniform in the mixed systems than the
      lamellar systems with fewer EC clusters present after several days in culture.
      Proliferation of hCB-ECs was higher for mixed cocultures during the first 24 h of
      coculture, and then declined dramatically suggesting that proliferation only
      contributed to network formation during the early stages of coculture. Proteome
      assay results show reduced solution levels, but no change in intracellular levels
      of angiogenic proteins in lamellar systems compared to mixed systems. These data
      suggest that mixing ECs and SMCs together favors the formation of EC networks to
      a greater extent than a lamellar arrangement in which ECs form a cell layer above
      a confluent, quiescent layer of SMCs.

PMID- 23171169
TI  - Prevalence, clinical associations, and impact of intimate partner violence among
      HIV-infected gay and bisexual men: a population-based study.
AB  - OBJECTIVES: Intimate partner violence (IPV) is a risk factor for HIV infection.
      Little is known, however, about the prevalence, clinical associations, and impact
      of IPV among patients living with HIV. METHODS: HIV-infected gay and bisexual men
      in Southern Alberta, Canada were screened for IPV between May 2009 and December
      2011. The associations with IPV of sociodemographic factors, psychological
      factors, clinical status, and HIV-related and HIV-unrelated hospitalizations,
      data for which were obtained from a regional database, were evaluated using
      Poisson regression. RESULTS: Of 687 gay and bisexual patients, 22.4% had
      experienced one or several types of IPV. Patients disclosing IPV were more likely
      to be Aboriginal [adjusted prevalence ratio (APR) = 2.48; 95% confidence interval
      (CI) 1.18-5.20], to be younger (APR/year = 0.97; 95% CI 0.95-0.99), to be victims
      of childhood abuse (APR = 4.27; 95% CI 2.84-6.41), to be smokers (APR = 2.53; 95%
      CI 1.59-4.00), to have had depression prior to HIV diagnosis (APR = 1.87; 95% CI
      1.10-3.16), to use ongoing psychiatric resources (APR = 3.53; 95% CI 2.05-6.10),
      to have recently participated in unprotected sex (APR = 2.29; 95% CI 1.10-4.77),
      and to have poor or fair vs. very good or excellent health-related quality of
      life (APR = 2.91; 95% CI 1.57-5.39). IPV was also associated with a higher rate
      of clinically relevant interruptions in care (APR = 1.95; 95% CI 1.23-3.08), a
      higher incidence of AIDS among patients presenting early to care (CD4 count >=
      200 cells/MUL; APR = 2.06; 95% CI 1.15-3.69), and an increased rate of HIV
      related hospitalizations [relative risk (RR) = 1.55; 95% CI 0.99-2.33],
      especially after HIV diagnosis was established (RR = 2.46; 95% CI 1.51-3.99).
      CONCLUSIONS: The prevalence of IPV is high among HIV-infected gay and bisexual
      men and is associated with poor social, psychiatric, and medical outcomes. IPV is
      an under-recognized social determinant of health in this community that may be
      amenable to meaningful clinical interventions.

PMID- 23171171
TI  - Direct growth of carbon nanofibers to generate a 3D porous platform on a metal
      contact to enable an oxygen reduction reaction.
AB  - For carbon nanotube-based electronics to achieve their full performance
      potential, it is imperative to minimize the contact resistance between macroscale
      metal contacts and the carbon nanotube (CNT) nanoelectrodes. We have developed a
      three-dimensional electrode platform that consists of carbon nanofibers (CNFs)
      that are directly grown on a metal contact, such as copper (Cu). Carbon nanofiber
      morphology can be tailored by adjusting the annealing time of a thin
      electrochemically deposited nickel catalyst layer on copper. We demonstrate that
      increasing the annealing time increases the amount of copper infused into the
      nickel catalyst layer. This reduces the carbon deposition rate, and consequently
      a more well-defined CNF 3D architecture can be fabricated. This direct growth of
      CNFs on a Cu substrate yields an excellent electron transfer pathway, with
      contact resistance between CNFs and Cu being comparable to that of a Cu-Cu
      interface. Furthermore, the excellent bonding strength between CNFs and Cu can be
      maintained over prolonged periods of ultrasonication. The porous 3D platform
      affixed with intertwined CNFs allows facile surface functionalization. Using a
      simple solution soaking procedure, the CNF surface has been successfully
      functionalized with iron(II) phthalocyanine (FePc). FePc functionalized CNFs
      exhibit excellent oxygen reduction capability, equivalent to platinum-carbon
      electrodes. This result demonstrates the technological promise of this new 3D
      electrode platform that can be exploited in other applications that include
      sensing, battery, and supercapacitors.

PMID- 23171172
TI  - Who you gonna' call?

PMID- 23171170
TI  - The effects of sex steroids on thyroid C cells and trabecular bone structure in
      the rat model of male osteoporosis.
AB  - Androgen deficiency is one of the major factors leading to the development of
      osteoporosis in men. Since calcitonin (CT) is a potent antiresorptive agent, in
      the present study we investigated the effects of androgen deficiency and
      subsequent testosterone and estradiol treatment on CT-producing thyroid C cells,
      skeletal and hormonal changes in middle-aged orchidectomized (Orx) rats. Fifteen
      month-old male Wistar rats were either Orx or sham-operated (SO). One group of
      Orx rats received 5 mg kg(-1)  b.w. testosterone propionate (TP) subcutaneously,
      while another group was injected with 0.06 mg kg(-1)  b.w. estradiol dipropionate
      (EDP) once a day for 3 weeks. A peroxidase-antiperoxidase method was applied for
      localization of CT in the C cells. The studies included ultrastructural
      microscopic observation of these cells. The metaphyseal region of the proximal
      tibia was measured histomorphometrically using an imagej public domain image
      processing program. TP or EDP treatment significantly increased C cell volume
      (Vc), volume densities (Vv) and serum CT concentration compared with the Orx
      animals. Administration of both TP and EDP significantly enhanced cancellous bone
      area (B.Ar), trabecular thickness (Tb.Th) and trabecular number (Tb.N) and
      reduced trabecular separation (Tb.Sp). Serum osteocalcin (OC) and urinary Ca
      concentrations were significantly lower after these treatments in comparison with
      Orx rats. These data suggest that testosterone and estradiol treatment in Orx
      middle-aged rats affect calcitonin-producing thyroid C cells, which may
      contribute to the bone protective effects of sex hormones in the rat model of
      male osteoporosis.

PMID- 23171174
TI  - Ten questions with .... David Mann.

PMID- 23171178
TI  - Medical device service and support.

PMID- 23171179
TI  - A manufacturing perspective: balancing safety issues with a customer's desire for
      self-service.

PMID- 23171180
TI  - An HTM perspective: it's time for a new service support model.

PMID- 23171181
TI  - Familiar themes in a changing world: AAMI survey identifies top medical device
      challenges.

PMID- 23171183
TI  - Get ready for your closeup: HTM professionals have key role with electronic
      health records.

PMID- 23171184
TI  - Generalizing FDA guidance on clinical decision support.

PMID- 23171185
TI  - Making things right: the art of the apology at work.

PMID- 23171186
TI  - ECRI vice president sees need for transparency, better information.

PMID- 23171188
TI  - 'A win on many fronts' the case for medical equipment inspectors.

PMID- 23171189
TI  - Electron microscopes.

PMID- 23171190
TI  - Calibrating touch-screen monitors.

PMID- 23171192
TI  - The high cost of increased 'productivity'.

PMID- 23171193
TI  - Electrocardiogram interference: a thing of the past?
AB  - This paper focuses on the problem of high and/or imbalanced electrode-skin
      impedances changing electrocardiogram (ECG) morphology. After reproducing ECG
      interference in a controlled laboratory setting-similar to what was observed
      during cardiopulmonary bypass surgery- and then understanding the cause, this
      knowledge was applied to clinical settings. Most interference was reduced by
      using electrode impedance meters and consistent skin prep.

PMID- 23171194
TI  - Reducing hospital noise: a review of medical device alarm management.
AB  - Increasing noise in hospital environments, especially in intensive care units
      (ICUs) and operating rooms (ORs), has created a formidable challenge for both
      patients and hospital staff. A major contributing factor for the increasing noise
      levels in these environments is the number of false alarms generated by medical
      devices. This study focuses on discovering best practices for reducing the number
      of false clinical alarms in order to increase patient safety and provide a quiet
      environment for both work and healing. The researchers reviewed Pub Med, Web of
      Knowledge and Google Scholar sources to obtain original journal research and
      review articles published through January 2012. This review includes 27
      critically important journal articles that address different aspects of medical
      device alarms management, including the audibility, identification, urgency
      mapping, and response time of nursing staff and different solutions to such
      problems. With current technology, the easiest and most direct method for
      reducing false alarms is to individualize alarm settings for each patient's
      condition. Promoting an institutional culture change that emphasizes the
      importance of individualization of alarms is therefore an important goal. Future
      research should also focus on the development of smart alarms.

PMID- 23171195
TI  - In service/support debate, throwing rocks won't help.

PMID- 23171196
TI  - Origins of charge noise in carbon nanotube field-effect transistor biosensors.
AB  - Determining the major noise sources in nanoscale field-effect transistor
      (nanoFET) biosensors is critical for improving bioelectronic interfaces. We use
      the carbon nanotube (CNT) FET biosensor platform to examine the noise generated
      by substrate interactions and surface adsorbates, both of which are present in
      current nanoFET biosensors. The charge noise model is used as a quantitative
      framework to show that insulating substrates and surface adsorbates are both
      significant contributors to the noise floor of CNT FET biosensors. Removing
      substrate interactions and surface adsorbates reduces the power spectral density
      of background voltage fluctuations by 19-fold.

PMID- 23171197
TI  - Measuring psychological development with the Rorschach.
AB  - The aim of this study was to develop and to provide an initial validation of a
      Rorschach index measuring developmental progress and growth. The Developmental
      Index (DI) was created in a 3-step, sequential strategy with adult and child data
      in which we (a) selected potential DI variables from quantitative research
      literature and from data available to us, (b) identified an optimal group of DI
      variables and created the DI equation using an independent nonpatient sample, and
      (c) provided an initial cross-validation of the DI using an independent clinical
      sample. Age and age rank categorization groups from normative data associated
      with the Wechsler intelligence scales (Wechsler, 2003, 2008) and contrasts
      between adults and children served as criteria for development. These samples
      include a large amount of data from a diverse international subject pool using
      the Comprehensive System of the Rorschach. Interim validity checks were
      undertaken to ensure the analytic strategy was sound. The DI includes 12
      variables with individual weights determined by regression analysis. The initial
      independent cross-validation of the DI with a clinical sample revealed that it
      discriminated well between children and adults. Thus, initial support for this
      scale as a measure of psychological development across cultures and geography was
      established, but future research is needed. Clinical implications and specific
      research needs are presented.

PMID- 23171198
TI  - Quantitative autistic traits ascertained in a national survey of 22 529 Japanese
      schoolchildren.
AB  - OBJECTIVE: Recent epidemiologic studies worldwide have documented a rise in
      prevalence rates for autism spectrum disorders (ASD). Broadening of diagnostic
      criteria for ASD may be a major contributor to the rise in prevalence,
      particularly if superimposed on an underlying continuous distribution of autistic
      traits. This study sought to determine the nature of the population distribution
      of autistic traits using a quantitative trait measure in a large national
      population sample of children. METHOD: The Japanese version of the Social
      Responsiveness Scale (SRS) was completed by parents on a nationally
      representative sample of 22 529 children, age 6-15. RESULTS: Social
      Responsiveness Scale scores exhibited a skewed normal distribution in the
      Japanese population with a single-factor structure and no significant relation to
      IQ within the normal intellectual range. There was no evidence of a natural
      'cutoff' that would differentiate populations of categorically affected children
      from unaffected children. CONCLUSION: This study provides evidence of the
      continuous nature of autistic symptoms measured by the SRS, a validated
      quantitative trait measure. The findings reveal how paradigms for diagnosis that
      rest on arbitrarily imposed categorical cutoffs can result in substantial
      variation in prevalence estimation, especially when measurements used for case
      assignment are not standardized for a given population.

PMID- 23171199
TI  - Multiple sorting systems for secretory granules ensure the regulated secretion of
      peptide hormones.
AB  - Prior to secretion, regulated peptide hormones are selectively sorted to
      secretory granules (SGs) at the trans-Golgi network (TGN) in endocrine cells.
      Secretogranin III (SgIII) appears to facilitate SG sorting process by tethering
      of protein aggregates containing chromogranin A (CgA) and peptide hormones to the
      cholesterol-rich SG membrane (SGM). Here, we evaluated the role of SgIII in SG
      sorting in AtT-20 cells transfected with small interfering RNA targeting SgIII.
      In the SgIII-knockdown cells, the intracellular retention of CgA was greatly
      impaired, and only a trace amount of CgA was localized within the vacuoles formed
      in the TGN, confirming the significance of SgIII in both the tethering of CgA
      containing aggregates and the establishment of the proper SG morphology. Although
      the intracellular retention of proopiomelanocortin (POMC) was considerably
      impaired in SgIII-knockdown cells, residual adrenocorticotropic hormone
      (ACTH)/POMC was still localized to some few remaining SGs together with another
      granin protein, secretogranin II (SgII), and was secreted in a regulated manner.
      Biochemical analyses indicated that SgII bound directly to the SGM in a
      cholesterol-dependent manner and was able to retain the aggregated form of POMC,
      revealing a latent redundancy in the SG sorting and retention mechanisms, that
      ensures the regulated secretion of bioactive peptides.

PMID- 23171200
TI  - Evaluation of an educational practice development programme for staff working in
      mental health inpatient environments.
AB  - This paper describes key components of a mental health practice development
      training programme, which aimed to translate into practice a deeper, more
      evidence-based understanding of the lived experience of service users detained
      under the Mental Health Act (1983/2007), using action research as the
      underpinning paradigm. The programme explored the myriad applications of the six
      categories of intervention initially proposed by Heron and the widespread
      applicability of solution-focused brief therapy. The programme evaluation used
      open-ended questionnaires in order to obtain participants' views on facilitation
      and workshop content, in addition to two focus groups. The aim of the evaluation
      was to provide insight into participants' experience of the programme. Feedback
      from participants reflected a high degree of skill acquisition and enhancement
      and a noticeable change in ward culture after completing the programme. Service
      user researchers were intimately involved during all stages of the design,
      implementation and analysis including service user interviews for Phase 1 and the
      education intervention element of the practice development programme.
      Implications for evidence-based mental health nursing practice, service user
      involvement in research and directions for future research are discussed.

PMID- 23171201
TI  - Quality of sexual life of women on oral contraceptive continued-regimen: pilot
      study.
AB  - INTRODUCTION: To date, women may use flexible oral contraceptive (OC) regimens.
      AIM: The aim of this study was to evaluate the quality of sexual life of healthy
      women on continued-regimen OCs. METHODS: Fifty women (age range 18-38) were
      enrolled. The Female Sexual Function Index (FSFI) and the Short Form-36 (SF-36)
      questionnaires were used to investigate, respectively, sexual behavior and the
      quality of life (QoL) of women on OC for 72 days with a 4-day hormone-free
      interval, for two cycles. Both the FSFI and the SF-36 were administered before
      starting OC intake, at the first (72-82 days) and the second (144-154 days)
      follow-ups. MAIN OUTCOME MEASURE: The main outcomes are the FSFI and the SF-36
      questionnaires. RESULTS: The FSFI score obtained at the first follow-up detected
      a worsening with respect to baseline score (P < 0.05). The score obtained at the
      second follow-up detected an improvement with respect to both the baseline and
      the first follow-up total scores (P < 0.05). QoL improved at the first follow-up
      only as regards body pain (P < 0.05), and at the second follow-up as regards:
      physical role, body pain, general health, vitality, and social function (P <
      0.05). CONCLUSIONS: The use of continued-regimen OCs is able to improve the
      sexual behavior and the QoL of women.

PMID- 23171202
TI  - Ivermectin inhibits the sporogony of Plasmodium falciparum in Anopheles gambiae.
AB  - BACKGROUND: When ingested in a blood meal, ivermectin has been shown to reduce
      the survivorship of Anopheles gambiae in the laboratory and field. Furthermore,
      ivermectin mass drug administrations in Senegal have been shown to reduce the
      proportion of Plasmodium falciparum-sporozoite-containing An. gambiae. This study
      addresses whether ivermectin inhibits sporogony of P. falciparum in An. gambiae.
      METHODS: Anophele gambiae s.s. G3 strain were fed two concentrations of
      ivermectin (LC25 and LC5) along with P. falciparum NF54 in human blood meals at
      staggered intervals. Mosquitoes ingested ivermectin concurrent with parasites
      (DPI 0), or at three (DPI 3), six (DPI 6), and nine (DPI 9) days post parasite
      ingestion, or three days prior (DPI -3) to parasite ingestion. Mosquitoes were
      dissected at seven, twelve or fourteen days post parasite ingestion and either
      oocyst or sporozoite prevalence was recorded. To determine if P. falciparum
      sporozoite-containing An. gambiae were more susceptible to ivermectin than
      uninfected controls, survivorship was recorded for mosquitoes which ingested P.
      falciparum or control blood meal on DPI 0 and then a second blood meal containing
      ivermectin (LC25) on DPI 14. RESULTS: Ivermectin (LC25) co-ingested (DPI 0) with
      parasites reduced the proportion of An. gambiae that developed oocysts (chi2 =
      15.4842, P = 0.0002) and sporozoites (chi2 = 19.9643, P < 0.0001). Ivermectin
      (LC25) ingested DPI 6 (chi2 = 8.5103, P = 0.0044) and 9 (chi2 = 14.7998, P <
      0.0001) reduced the proportion of An. gambiae that developed sporozoites but not
      when ingested DPI 3 (chi2 = 0.0113, P = 1). Ivermectin (LC5) co-ingested (DPI 0)
      with parasites did not reduce the proportion of An. gambiae that developed
      oocysts (chi2 = 4.2518, P = 0.0577) or sporozoites (chi2 = 2.3636, P = 0.1540),
      however, when ingested DPI -3 the proportion of An. gambiae that developed
      sporozoites was reduced (chi2 = 8.4806, P = 0.0047). Plasmodium falciparum
      infection significantly reduced the survivorship of An. gambiae that ingested
      ivermectin (LC25) on DPI 14 compared to control mosquitoes that ingested a
      primary blood meal without parasites (chi2 = 4.97, P = 0.0257). CONCLUSIONS:
      Ivermectin at sub-lethal concentrations inhibits the sporogony of P. falciparum
      in An. gambiae. These findings support the utility of ivermectin for P.
      falciparum transmission control.

PMID- 23171203
TI  - High viremia and low level of transmitted drug resistance in anti-retroviral
      therapy-naive perinatally-infected children and adolescents with HIV-1 subtype C
      infection.
AB  - BACKGROUND: High plasma viremia in HIV-1 infection is associated with rapid CD4
      cell decline and faster disease progression. Children with HIV infection have
      high viral loads, particularly in early childhood. In this study we sought to
      understand the relationship between duration of HIV-1 infection and viral
      dynamics among perinatally-infected children and adolescents in India along with
      transmitted drug resistance in this population. METHODS: During 2007-2011, cross
      sectional samples were collected from ART-naive children (n = 105) with
      perinatally-acquired HIV infection, aged 2-16 years from Bangalore, India. CD4
      counts, viral load and in-house genotyping were performed and transmitted drug
      resistance mutations were identified using the World Health Organization
      recommendations for Surveillance of Drug Resistance Mutations (SDRM_2009) list.
      RESULTS: Among 105 children studied, 73.3% (77/105) were asymptomatic, but had a
      median viral load of 5.24 log copies/mL (IQR 4.62-5.66). In the adolescent age
      group, 54% (21/39) had high levels of viremia (median 5.14 log copies/mL) but
      were asymptomatic. HIV-1 subtyping identified 98% strains (103/105) as subtype C;
      one A1 and one unique recombinant form (URF). Transmitted NRTI resistance was
      1.9% (2/105); NNRTI resistance was 4.8% (5/105) and overall prevalence of
      transmitted drug resistance was 5.7% (6/105). CONCLUSIONS: The high burden of
      plasma viremia found among untreated asymptomatic adolescents needs to be
      addressed both from an individual angle to halt disease progression, and from a
      public health perspective to arrest horizontal transmission. The low level of
      transmitted drug resistance among perinatally-infected children is reassuring;
      however with improving ART access globally, regular genotyping surveillance is
      indicated.

PMID- 23171204
TI  - Factors associated with subsequent eye care for children in Taiwan: a population
      based historical cohort study.
AB  - PURPOSE: To investigate patterns and factors associated with subsequent eye care
      for Taiwan's children. METHODS: We conducted a population-based historical cohort
      study of 2464 children aged between 3 and 12 years old from the 2005 National
      Health Interview Survey (NHIS). Participants' ocular conditions were identified
      based on 2005 NHIS questionnaire answers given by caregivers. Subsequent eye care
      data was obtained from 2006 and 2007 National Health Insurance claim data. Eye
      care related to these children's ocular conditions was defined by physician's
      diagnosis using the International Classification of Diseases version 9 clinical
      modification codes. Poisson regression with robust variance estimation was used
      to determine factors associated with eye care use. RESULTS: Of the 2464 children,
      712 (28.9%) had ocular conditions in 2005, and 56.5% and 44.7% of them didn't
      receive eye care during the subsequent 1- and 2-year periods, respectively. Among
      those with ocular conditions, the 3-4-year-olds were least likely to receive eye
      care in the subsequent 1 and 2 years. Children with highly educated fathers were
      more likely to receive eye care in the subsequent 1-year period. Sex, family
      income, level of mother's education, residential area and eye care resources were
      not significant factors for children with ocular conditions receiving subsequent
      eye care within either 1 or 2 years. CONCLUSIONS: Despite the fact that Taiwan
      has a National Health Insurance Program, lack of subsequent eye care remains
      high, even when a child's ocular condition is known by the caregiver.
      Determinants associated with follow-up eye care must be considered when designing
      eye care enhancing programs for children.

PMID- 23171205
TI  - A meta-analysis of primary external dacryocystorhinostomy with and without
      mitomycin C.
AB  - OBJECTIVE: To assess the efficacy and safety of local application of
      intraoperative mitomycin C (MMC) at the osteotomy site in primary external
      dacryocystorhinostomy (EX-DCR). METHODS: A comprehensive literature search of the
      Cochrane Library, PubMed and Embase was undertaken to identify relevant trials
      comparing EX-DCR with MMC (MMC group, from 0.2-1.0 mg/mL) and without MMC
      (control group). A total of nine randomized controlled trials (RCTs) were
      selected and a meta-analysis performed on the results of success rates, which
      were defined as patency of the nasolacrimal canal and symptomatic improvement.
      Statistical analysis was performed using RevMan 5.0 software. RESULTS: Nine RCTs
      reporting on a total of 562 DCRs including patients in the age range 30-57 years
      were included in the meta-analysis. However, the total number of males and
      females could not be determined as only four RCTs reported on this aspect. There
      was a significantly higher success rate in the MMC group in comparison with the
      control group (odds ratio, OR, 2.11; 95% confidence interval, CI, 1.19-3.74, P =
      0. 01). In two RCTs, the mean osteotomy size 6 months postoperatively was
      significantly larger in the MMC group than in the control group (about 27mm(2) in
      the MMC group versus about 12mm(2) in the control group in the first study, and
      about 22mm(2) in the MMC group versus about 18mm(2) in the control group in the
      second study, P < 0.005). No intraoperative or postoperative complications except
      two cases with delayed healing of the external skin wound were recorded in the
      MMC group. CONCLUSION: Intraoperative MMC application seems to be a safe adjuvant
      that could reduce the closure rate of the osteotomy site after primary EX-DCR.
      Further well-organized, prospective, randomized studies involving larger patient
      numbers divided into subgroups for different concentrations of locally applied
      MMC are warranted.

PMID- 23171206
TI  - Epidemic adenoviral keratoconjunctivitis possibly related to ophthalmological
      procedures in a neonatal intensive care unit: lessons from an outbreak.
AB  - PURPOSE: Epidemic adenoviral keratoconjunctivitis can spread rapidly among
      preterm infants who frequently undergo ophthalmological examination. Here we
      present our experience on a nosocomial outbreak that affected 8 nursery staff
      members and 26 premature infants. We focus on the presentation and progress of
      the outbreak, the diagnosis of the disease and the measures taken for its
      control. METHODS: Data were collected from patients' files and records of the
      infection control team. Conjunctival swabs were collected to perform direct
      fluorescent assay (DFA) and viral culture. Diagnosis was made according to
      clinical evidence and/or detection of the virus. Statistical analysis was
      performed using SPSS 15.0 statistical software. RESULTS: Infection was introduced
      to our unit after a laser photocoagulation procedure of a 28-week gestational
      infant and circulated rapidly within the unit due to direct transmission through
      contaminated medical equipment, fomites and hands of nursery staff members.
      Neither the patients, nor the nursery staff members developed systemic symptoms.
      While DFA tests were positive in seven infants, culture positivity could be
      demonstrated in only three infants. Contact and droplet precautions were
      implemented with the recommendation of the infection control team. No recurrence
      occurred after definition of the last case on the 32nd day. CONCLUSION:
      Ophthalmologic procedures continue to be a potential source of adenovirus
      outbreaks. However, negligence of contact measures during routine daily nursing
      care seems to be a more important contributing factor for rapid spread. Strict
      adherence to appropriate aseptic procedures is required to prevent this
      potentially hazardous infection in preterm infants.

PMID- 23171207
TI  - Prevalence of lens opacities in Asian Malays.
AB  - PURPOSE: To describe the prevalence of lens opacities and cataract surgery in an
      older Malay population in Singapore. METHODS: The Singapore Malay Eye Study is a
      population-based cross-sectional study of 3280 (78.7% response rate) Malay adults
      aged 40-80 years. Participants underwent a standardized clinical eye examination.
      Digital slit-lamp and retroillumination photographs were taken of both eyes of
      each participant and graded for age-related nuclear, cortical and posterior
      subcapsular (PSC) cataract, following the Wisconsin Cataract Grading System.
      Other lens opacities, including retrodots and vacuoles, were also graded.
      Information on medical and lifestyle factors was collected using questionnaires.
      The study sample was directly age-standardized to the Malay population in
      Singapore using the 2000 Singapore population census. RESULTS: A total of 3054
      (97.7%) and 3113 (99.6%) participants had gradable Topcon slit lamp and Neitz
      photographs, respectively. The overall age-adjusted prevalence of any cataract
      was 29.1%, and that of nuclear, cortical and PSC cataract were 12.9% (95%
      confidence interval, CI, 11.2-13.1%), 21.2% (95% CI 19.8-22.7%) and 9.7% (95% CI
      8.8-10.8%), respectively. Age-adjusted prevalence of cataract surgery was 4.7%
      (95% CI 4.2-5.4%). Prevalence of all three cataract types and cataract surgery
      increased with age. Age-adjusted prevalence for retrodots and vacuoles were 19.7%
      (95% CI 18.3-21.1%) and 64.3% (95% CI 61.1-67.6%), respectively. Retrodots were
      found to be associated with prevalence of all three cataract types, while
      vacuoles were associated with cortical and PSC cataract prevalence. CONCLUSION:
      Lens opacities were common in this urban Malay population. Retrodots and vacuoles
      were found to be associated with age-related cataract.

PMID- 23171208
TI  - Measuring vision-specific quality of life among adults in Fiji.
AB  - PURPOSE: To evaluate an 18-item vision-specific quality-of-life questionnaire
      designed for use with adults in Fiji. METHODS: Participants in a population-based
      cross-sectional survey selected by multistage random sampling from those aged
      >=40 years living on Fiji's main island had distance and near visual acuity
      measured. Those with presenting vision impairment (<6/18) and/or presbyopia (<N8)
      and every third participant with normal presenting distance vision answered an
      interview-based questionnaire. RESULTS: Of 1381 participants, 928 were eligible
      to answer the questionnaire. Of these, 921 provided valid responses to more than
      half the items and were the subject of analysis. The questionnaire conformed with
      a rating scale model: with the possible exception of one item, a single scale was
      formed, which had considerable range and many items well spaced. Estimates of
      relative validity suggested that rating and Likert scales constructed from the
      data had similar criterion validity discriminating between those with and without
      vision problems. The spacing and hierarchy of a three-response category model
      ("no problem," "little/moderate difficulty," "lot of difficulty/unable to do
      because of my vision"), were little influenced by sex, ethnicity or urban versus
      rural residence. Near vision tasks associated with print and very small objects,
      mobile phone use, sewing/weaving, and preparing lentils/rice/grains were ranked
      most difficult. CONCLUSION: Although the analysis showed the 18-item
      questionnaire to be an adequate tool for assessing the impact of vision reduction
      on quality of life among adults in Fiji, further community consultation and item
      modification would likely deliver a more efficacious instrument.

PMID- 23171209
TI  - Paralytic strabismus in South African Black and mixed race children--a 15-year
      clinic-based review.
AB  - PURPOSE: To describe the demographics and clinical profile of paralytic
      strabismus in South African black and mixed race children seen at a tertiary
      pediatric eye clinic. METHODS: A retrospective, descriptive case series of
      patients younger than 14 years diagnosed with paralytic strabismus at the Red
      Cross War Memorial Children's Hospital in Cape Town, between 1996 and 2010.
      RESULTS: A total of 166 children were studied. Of these, 74% were of mixed race
      descent while 26% were black. The most commonly affected cranial nerve was the
      fourth (52%). The sixth nerve was involved in 39% of cases, while 5% and 4% had
      third nerve palsy and multiple cranial palsies, respectively. The majority of
      mixed race children (58%) had fourth cranial nerve palsies, while 54% of black
      children had sixth nerve palsies. The most common cause of paralytic strabismus
      was congenital (55%), followed by trauma (18%). CONCLUSION: In this clinic-based
      study, paralytic strabismus was more common in mixed race children. Fourth nerve
      palsies predominated in mixed race children, whereas the majority of black
      children had sixth nerve palsies. Further population-based research is necessary
      to identify the determinants of ocular cranial nerve palsy in African children.

PMID- 23171210
TI  - Causes of blindness and visual impairment among students in integrated schools
      for the blind in Nepal.
AB  - PURPOSE: To identify the causes of blindness and visual impairment among students
      in integrated schools for the blind in Nepal. METHODS: A total of 778 students
      from all 67 integrated schools for the blind in Nepal were examined using the
      World Health Organization/Prevention of Blindness Eye Examination Record for
      Children with Blindness and Low Vision during the study period of 3 years.
      RESULTS: Among 831 students enrolled in the schools, 778 (93.6%) participated in
      the study. Mean age of students examined was 13.7 years, and the male to female
      ratio was 1.4:1. Among the students examined, 85.9% were blind, 10% had severe
      visual impairment and 4.1% were visually impaired. The cornea (22.8%) was the
      most common anatomical site of visual impairment, its most frequent cause being
      vitamin A deficiency, followed by the retina (18.4%) and lens (17.6%). Hereditary
      and childhood factors were responsible for visual loss in 27.9% and 22.0% of
      students, respectively. Etiology could not be determined in 46% of cases.
      Overall, 40.9% of students had avoidable causes of visual loss. Vision could be
      improved to a level better than 6/60 in 3.6% of students refracted. CONCLUSION:
      More than one third of students were visually impaired for potentially avoidable
      reasons, indicating lack of eye health awareness and eye care services in the
      community. The cause of visual impairment remained unknown in a large number of
      students, which indicates the need for introduction of modern diagnostic tools.

PMID- 23171213
TI  - C8-heteroaryl-2'-deoxyguanosine adducts as conformational fluorescent probes in
      the NarI recognition sequence.
AB  - The optical, redox, and electronic properties of C(8)-heteroaryl-2'
      deoxyguanosine (dG) adducts with C(8)-substituents consisting of furyl ((Fur)dG),
      pyrrolyl ((Pyr)dG), thienyl ((Th)dG), benzofuryl ((Bfur)dG), indolyl ((Ind)dG),
      and benzothienyl ((Bth)dG) are described. These adducts behave as fluorescent
      nucleobase probes with emission maxima from 379 to 419 nm and fluorescence
      quantum yields (Phi(fl)) in the 0.1-0.8 range in water at neutral pH. The probes
      exhibit quenched fluorescence with increased solvent viscosity and decreased
      solvent polarity. The (Fur)dG, (Bfur)dG, (Ind)dG, and (Bth)dG derivatives were
      incorporated into the G(3) position of the 12-mer oligonucleotide 5'
      CTCG(1)G(2)CG(3)CCATC-3' that contains the recognition sequence of the NarI Type
      II restriction endonuclease. This sequence is widely used to study the biological
      activity (mutagenicity) of C(8)-arylamine-dG adducts with adduct conformation
      (anti vs syn) playing a critical role in the biological outcome. The modified
      NarI(X = (Fur)G, (Ind)G, (Bfur)G, or (Bth)G) oligonucleotides were hybridized to
      the complementary strand containing either C (NarI'(C)) or G (NarI'(G)) opposite
      the probe. The duplex structures were characterized by UV melting temperature
      analysis, fluorescence spectroscopy, collisional fluorescence quenching studies,
      and circular dichroism (CD). The emission of the probes showed sensitivity to the
      opposing base in the duplex, and suggested the utility of fluorescence
      spectroscopy to monitor probe conformation.

PMID- 23171212
TI  - Strategies of digital fundus photography for screening diabetic retinopathy in a
      diabetic population in urban China.
AB  - PURPOSE: To evaluate the effect of mydriasis and different field strategies on
      technical failure, probability to refer diabetic retinopathy (DR, sensitivity)
      and probability not to refer patients without DR (specificity) of digital
      photography in screening with a fundus camera. METHODS: A total of 531 patients
      with diabetes underwent fundus photography with cross-combinations of
      mydriasis/nonmydriasis and single-field/two-field strategies, followed by slit
      lamp biomicroscopic examination by a trained ophthalmologist. Fundus photographs
      were graded independently by another experienced ophthalmologist. Calculations
      were first based on cases with non-gradable images treated as being referred and
      then with them excluded. RESULTS: Percentages of DR and referable DR in this
      patient cohort were 22.4% and 7.7%, respectively, based on slit lamp
      biomicroscopic examination. Mydriasis significantly reduced the technical failure
      rate from 27.1% to 8.3% under a single-field strategy, and from 28.2% to 8.9%
      under a two-field strategy. As compared to the single-field strategy, the two
      field strategy increased sensitivity from 75.6% to 87.8% without mydriasis and
      from 73.2% to 90.2% with mydriasis. Mydriasis increased specificity from 68.8% to
      84.3% in the single-field strategy and from 64.7% to 81.6% in the two-field
      strategy. Had the subjects with non-gradable images been excluded, the two-field
      strategy without mydriasis reported sensitivity of 85.7% and specificity of
      91.6%. CONCLUSIONS: Both mydriasis and the two-field strategy are useful in
      photographic screening tests. Technical failure should be taken into
      consideration when screening strategies for DR are determined.

PMID- 23171211
TI  - Prior elicitation and Bayesian analysis of the Steroids for Corneal Ulcers Trial.
AB  - PURPOSE: To elicit expert opinion on the use of adjunctive corticosteroid therapy
      in bacterial corneal ulcers. To perform a Bayesian analysis of the Steroids for
      Corneal Ulcers Trial (SCUT), using expert opinion as a prior probability.
      METHODS: The SCUT was a placebo-controlled trial assessing visual outcomes in
      patients receiving topical corticosteroids or placebo as adjunctive therapy for
      bacterial keratitis. Questionnaires were conducted at scientific meetings in
      India and North America to gauge expert consensus on the perceived benefit of
      corticosteroids as adjunct treatment. Bayesian analysis, using the questionnaire
      data as a prior probability and the primary outcome of SCUT as a likelihood, was
      performed. For comparison, an additional Bayesian analysis was performed using
      the results of the SCUT pilot study as a prior distribution. RESULTS: Indian
      respondents believed there to be a 1.21 Snellen line improvement, and North
      American respondents believed there to be a 1.24 line improvement with
      corticosteroid therapy. The SCUT primary outcome found a non-significant 0.09
      Snellen line benefit with corticosteroid treatment. The results of the Bayesian
      analysis estimated a slightly greater benefit than did the SCUT primary analysis
      (0.19 lines verses 0.09 lines). CONCLUSION: Indian and North American experts had
      similar expectations on the effectiveness of corticosteroids in bacterial corneal
      ulcers; that corticosteroids would markedly improve visual outcomes. Bayesian
      analysis produced results very similar to those produced by the SCUT primary
      analysis. The similarity in result is likely due to the large sample size of SCUT
      and helps validate the results of SCUT.

PMID- 23171214
TI  - Unraveling the mechanisms of nonradiative deactivation in model peptides
      following photoexcitation of a phenylalanine residue.
AB  - The mechanisms of nonradiative deactivation of a phenylalanine residue after near
      UV photoexcitation have been investigated in an isolated peptide chain model (N
      acetylphenylalaninylamide, NAPA) both experimentally and theoretically. Lifetime
      measurements at the origin of the first pipi* state of jet-cooled NAPA molecules
      have shown that (i) among the three most stable conformers of the molecule, the
      folded conformer NAPA B is ~50-times shorter lived than the extended major
      conformer NAPA A and (ii) this lifetime is virtually insensitive to deuteration
      at the NH(2) and NH sites. Concurrent time-dependent density functional theory
      (TDDFT) based nonadiabatic dynamics simulations in the full dimensionality,
      carried out for the NAPA B conformer, provided direct insights on novel classes
      of ultrafast deactivation mechanisms, proceeding through several conical
      intersections and leading in fine to the ground state. These mechanisms are found
      to be triggered either (i) by a stretch of the N(Phe)H bond, which leads to an H
      transfer to the ring, or (ii) by specific backbone amide distortions. The
      potential energy surfaces of the NAPA conformers along these critical pathways
      have been characterized more accurately using the coupled cluster doubles (CC2)
      method and shown to exhibit barriers that can be overcome with moderate excess
      energies. These results analyzed in the light of the experimental findings
      enabled us to assign the short lifetime of NAPA B conformer to a number of easily
      accessible exit channels from the initial pipi* surface, most importantly the one
      involving a transfer of electronic excitation to an npi* surface, induced by
      distortions of the backbone peptide bond.

PMID- 23171215
TI  - Enzymatically structured emulsions in simulated gastrointestinal environment:
      impact on interfacial proteolysis and diffusion in intestinal mucus.
AB  - Fundamental knowledge of physicochemical interactions in the gastrointestinal
      environment is required in order to support rational designing of protein
      stabilized colloidal food and pharmaceutical delivery systems with controlled
      behavior. In this paper, we report on the colloidal behavior of emulsions
      stabilized with the milk protein sodium caseinate (Na-Cas), and exposed to
      conditions simulating the human upper gastrointestinal tract. In particular, we
      looked at how the kinetics of proteolysis was affected by adsorption to an oil
      water interface in emulsion and whether the proteolysis and the emulsion
      stability could be manipulated by enzymatic structuring of the interface. After
      cross-linking with the enzyme transglutaminase, the protein was digested with use
      of an in vitro model of gastro-duodenal proteolysis in the presence or absence of
      physiologically relevant surfactants (phosphatidylcholine, PC; bile salts, BS).
      Significant differences were found between the rates of digestion of Na-Cas cross
      linked in emulsion (adsorbed protein) and in solution. In emulsion, the digestion
      of a population of polypeptides of M(r) ca. 50-100 kDa was significantly retarded
      through the gastric digestion. The persistent interfacial polypeptides maintained
      the original emulsion droplet size and prevented the system from phase
      separating. Rapid pepsinolysis of adsorbed, non-cross-linked Na-Cas and its
      displacement by PC led to emulsion destabilization. These results suggest that
      structuring of emulsions by enzymatic cross-linking of the interfacial protein
      may affect the phase behavior of emulsion in the stomach and the gastric
      digestion rate in vivo. Measurements of zeta-potential revealed that BS displaced
      the remaining protein from the oil droplets during the simulated duodenal phase
      of digestion. Diffusion of the postdigestion emulsion droplets through ex vivo
      porcine intestinal mucus was only significant in the presence of BS due to the
      high negative charge these biosurfactants imparted to the droplets. This implies
      that the electrostatic repulsion produced can prevent the droplets from being
      trapped by the mucus matrix and facilitate their transport across the small
      intestine mucosal barrier.

PMID- 23171216
TI  - Using protein microarray technology to screen anti-ERCC1 monoclonal antibodies
      for specificity and applications in pathology.
AB  - BACKGROUND: An antibody with cross-reactivity can create unexpected side effects
      or false diagnostic reports if used for clinical purposes. ERCC1 is being
      explored as a predictive diagnostic biomarker for cisplatin-based chemotherapy.
      High ERCC1 expression is linked to drug resistance on cisplatin-based
      chemotherapy. 8F1 is one of the most commonly used monoclonal antibodies for
      evaluating ERCC1 expression levels in lung cancer patient tissues, but it has
      been noted that this antibody cross-reacts with an unknown protein. RESULTS: By
      using a high density protein microarray chip technology, we discovered that 8F1
      not only reacts with its authentic target, ERCC1, but also cross-reacts with an
      unrelated nuclear membrane protein, PCYT1A. The cross-reactivity is due to a
      common epitope presented on these two unrelated proteins. Similar to the
      subcellular localization of ERCC1, IHC tests demonstrated that PCYT1A is
      localized mainly on nuclear membrane. In this study, we also discovered that the
      PCYT1A gene expression level is significantly higher than the ERCC1 gene
      expression level in a certain population of lung cancer patient tissue samples.
      To develop the best monoclonal antibody for ERCC1 IHC analysis, 18 monoclonal
      antibodies were generated and 6 of them were screened against our protein
      microarray chip. Two clones showed high mono-specificity on the protein
      microarray chip test and both worked for the IHC application. CONCLUSION: In
      summary, the 8F1 clone is not suitable for ERCC1 IHC assay due to its cross
      reactivity with PCYT1A protein. Two newly generated monoclonal antibodies, 4F9
      and 2E12, demonstrated ultra-specificity against ERCC1 protein and superior
      performance for IHC analyses.

PMID- 23171217
TI  - Is a change in mode of travel to school associated with a change in overall
      physical activity levels in children? Longitudinal results from the SPEEDY study.
AB  - BACKGROUND: Children who use active modes of travel (walking or cycling) to
      school are more physically active than those who use passive (motorised) modes.
      However, less is known on whether a change in mode of travel to school is
      associated with a change in children's physical activity levels. The purpose of
      this analysis was to investigate the association between change in mode of travel
      to school and change in overall physical activity levels in children. METHODS:
      Data from 812 9-10 year old British children (59% girls) who participated in the
      SPEEDY study were analysed. During the summer terms of 2007 and 2008 participants
      completed a questionnaire and wore an accelerometer for at least three days. Two
      level multiple linear regression models were used to explore the association
      between change in usual mode of travel to school and change in objectively
      measured time spent in MVPA. RESULTS: Compared to children whose reported mode of
      travel did not change, a change from a passive to an active mode of travel was
      associated with an increase in daily minutes spent in MVPA (boys: beta 11.59, 95%
      CI 0.94 to 22.24; girls: beta 11.92, 95% CI 5.00 to 18.84). This increase
      represented 12% of boys' and 13% of girls' total daily time spent in MVPA at
      follow-up. CONCLUSION: This analysis provides further evidence that promoting
      active travel to school may have a role in contributing to increasing physical
      activity levels in children.

PMID- 23171218
TI  - Transcriptional and metabolomic analysis of Ascophyllum nodosum mediated freezing
      tolerance in Arabidopsis thaliana.
AB  - BACKGROUND: We have previously shown that lipophilic components (LPC) of the
      brown seaweed Ascophyllum nodosum (ANE) improved freezing tolerance in
      Arabidopsis thaliana. However, the mechanism(s) of this induced freezing stress
      tolerance is largely unknown. Here, we investigated LPC induced changes in the
      transcriptome and metabolome of A. thaliana undergoing freezing stress. RESULTS:
      Gene expression studies revealed that the accumulation of proline was mediated by
      an increase in the expression of the proline synthesis genes P5CS1 and P5CS2 and
      a marginal reduction in the expression of the proline dehydrogenase (ProDH) gene.
      Moreover, LPC application significantly increased the concentration of total
      soluble sugars in the cytosol in response to freezing stress. Arabidopsis sfr4
      mutant plants, defective in the accumulation of free sugars, treated with LPC,
      exhibited freezing sensitivity similar to that of untreated controls. The 1H NMR
      metabolite profile of LPC-treated Arabidopsis plants exposed to freezing stress
      revealed a spectrum dominated by chemical shifts (delta) representing soluble
      sugars, sugar alcohols, organic acids and lipophilic components like fatty acids,
      as compared to control plants. Additionally, 2D NMR spectra suggested an increase
      in the degree of unsaturation of fatty acids in LPC treated plants under freezing
      stress. These results were supported by global transcriptome analysis.
      Transcriptome analysis revealed that LPC treatment altered the expression of 1113
      genes (5%) in comparison with untreated plants. A total of 463 genes (2%) were up
      regulated while 650 genes (3%) were down regulated. CONCLUSION: Taken together,
      the results of the experiments presented in this paper provide evidence to
      support LPC mediated freezing tolerance enhancement through a combination of the
      priming of plants for the increased accumulation of osmoprotectants and
      alteration of cellular fatty acid composition.

PMID- 23171219
TI  - Hermansky-Pudlak syndrome: pigmentary and non-pigmentary defects and their
      pathogenesis.
AB  - Hermansky-Pudlak syndrome (HPS) is an autosomal recessive and genetically
      heterogeneous disorder characterized by oculocutaneous albinism, bleeding
      tendency, and ceroid deposition, which likely leads to deleterious lesions in
      lungs, heart, and other organs. Currently, nine genes have been identified as
      causative for HPS in humans. Their pathological effects are attributable to the
      disrupted biogenesis of lysosome-related organelles (LROs) existing in multiple
      cell types or tissues, causing the pigmentory and non-pigmentory defects. This
      review focuses on the functional aspects of HPS genes in regulating LRO
      biogenesis and signal transduction. The understanding of these mechanisms expands
      our knowledge about the involvement of lysosomal trafficking in the targeting of
      cargoes for constitutive transport, degradation, and secretion. This opens an
      avenue to the pathogenesis of lysosomal trafficking disorders at the cellular and
      developmental levels.

PMID- 23171220
TI  - Competition on productivity gradients -- what do we expect?
AB  - Many experimental studies have quantified how the effects of competition vary
      with habitat productivity, with the results often interpreted in terms of the
      ideas of Grime and Tilman. Unfortunately, these ideas are not relevant to many
      experiments, and so we develop an appropriate resource competition model and use
      this to explore the effects of habitat productivity on the intensity of
      competition. Several mechanisms influencing the productivity-competition
      intensity relationship are identified, and these mechanisms explored using two
      classic data sets. In both cases, there is good agreement between the model
      predictions and empirical patterns. Quantification of the mechanisms identified
      by the models will allow the development of a simple predictive theory linking
      measures of the intensity of competition with ecosystem-level properties.

PMID- 23171221
TI  - A malicious masquerader.

PMID- 23171222
TI  - PER3 and ADORA2A polymorphisms impact neurobehavioral performance during sleep
      restriction.
AB  - The objective of the study was to determine whether ADORA2A or PER3 polymorphisms
      contribute to individual responsivity to sleep restriction. Nineteen healthy
      adults (ages 18-39, 11 males, 8 females) underwent sleep restriction (SR) which
      consisted of seven nights of 3 h time in bed (TIB) (04:00-07:00). SR was preceded
      by seven in-laboratory nights of 10 h TIB (21:00-07:00) and followed by three
      nights of 8 h TIB (23:00-07:00). Volunteers underwent psychomotor vigilance,
      objective alertness, and subjective sleepiness assessments throughout. Volunteers
      were genotyped for the PER3 VNTR polymorphism (PER3(4/4) n = 7; PER3(4/5) n = 10;
      PER3(5/5) n = 2) and the ADORA2A c.1083T>C polymorphism, (ADORA2A(C) (/T) n = 9;
      ADORA2A(T) (/T) n = 9; ADORA2A(C) (/C) n = 1) using polymerase chain reaction
      (PCR). Separate mixed-model anovas were used to assess contributions of ADORA2A
      and PER3 polymorphisms. Results showed that PER3(4/4) and ADORA2A(C/T)
      individuals expressed greater behavioral resiliency to SR compared to PER(4/5)
      and ADORA2A(T/T) individuals. Our findings contrast with previously reported non
      significant effects for the PER3 polymorphism under a less challenging sleep
      restriction regimen (4 h TIB per night for five nights). We conclude that PER3
      and ADORA2A polymorphisms become more behaviorally salient with increasing
      severity and/or duration of sleep restriction (based on psychomotor vigilance).
      Given the small sample size these results are preliminary and require
      replication.

PMID- 23171223
TI  - Alvimopan for prevention of postoperative paralytic ileus in radical cystectomy
      patients: a cost-effectiveness analysis.
AB  - WHAT'S KNOWN ON THE SUBJECT? AND WHAT DOES THE STUDY ADD?: No cost-effectiveness
      studies exist in patients after radical cystectomy for the routine use of
      alvimopan for the prevention of postoperative ileus. The present study provides a
      reasonable estimate of the cost-effectiveness of alvimopan for the prevention of
      postoperative ileus in the patient after radical cystectomy. OBJECTIVE: To
      determine if the cost of administering alvimopan, to help restore bowel function
      after abdominal surgery, to all patients undergoing radical cystectomy (RC) is
      cost prohibitive. PATIENTS AND METHODS: A cost-effective analysis was conducted
      from a healthcare payer perspective using a decision-tree model that incorporated
      direct healthcare costs and probabilities associated with the possible events and
      outcomes. Sensitivity analyses were conducted on the influence of the cost and
      effectiveness of the drug, the probability of POI in RC patients, and the
      extended length of stay (LOS) as a result of POI. Precision in estimates was
      determined using probabilistic sensitivity analyses with 5000 Monte-Carlo
      simulations. RESULTS: Under the base case assumption, the additional cost of a
      patient's LOS related to POI was $10 246 per person. Under the assumption that
      15.6% of patients will have POI, the mean cost associated with POI in a cohort of
      patients not treated with alvimopan was $1597 (90% confidence interval [CI] $1335
      1875) per patient. Conversely, the routine use of alvimopan for all patients
      undergoing RC was associated with a mean POI-associated cost of $1495(90% CI
      $1312-1696) per person, which represents the cost of alvimopan ($700 per
      hospitalisation) and a 50% reduction in the rate of POI. Sensitivity analyses
      revealed that there is a cost savings with the routine use of alvimopan under the
      following conditions: the POI results in extending LOS by >=3.5 days, POI occurs
      in >=14% of patients undergoing RC, or the drug results in a relative risk
      reduction of >=44%. CONCLUSIONS: Routine use of perioperative alvimopan may not
      be cost prohibitive because of its influence on POI rate and associated costs.
      The cost-effectiveness of alvimopan is influenced by the POI incidence and the
      degree to which the drug can decrease the LOS.

PMID- 23171224
TI  - Methyl-isobutyl amiloride reduces brain Lac/NAA, cell death and microglial
      activation in a perinatal asphyxia model.
AB  - Na+/H+ exchanger (NHE) blockade attenuates the detrimental consequences of
      ischaemia and reperfusion in myocardium and brain in adult and neonatal animal
      studies. Our aim was to use magnetic resonance spectroscopy (MRS) biomarkers and
      immunohistochemistry to investigate the cerebral effects of the NHE inhibitor,
      methyl isobutyl amiloride (MIA) given after severe perinatal asphyxia in the
      piglet. Eighteen male piglets (aged < 24 h) underwent transient global cerebral
      hypoxia-ischaemia and were randomized to (i) saline placebo; or (ii) 3 mg/kg
      intravenous MIA administered 10 min post-insult and 8 hourly thereafter. Serial
      phosphorus-31 (31P) and proton (1H) MRS data were acquired before, during and up
      to 48 h after hypoxia-ischaemia and metabolite-ratio time-series Area under the
      Curve (AUC) calculated. At 48 h, histological and immunohistochemical assessments
      quantified regional tissue injury. MIA decreased thalamic lactate/N
      acetylaspartate and lactate/creatine AUCs (both p < 0.05) compared with placebo.
      Correlating with improved cerebral energy metabolism, transferase mediated
      biotinylated d-UTP nick end-labelling (TUNEL) positive cell density was reduced
      in the MIA group in cerebral cortex, thalamus and white matter (all p < 0.05) and
      caspase 3 immunoreactive cells were reduced in pyriform cortex and caudate
      nucleus (both p < 0.05). Microglial activation was reduced in pyriform and
      midtemporal cortex (both p < 0.05). Treatment with MIA starting 10 min after
      hypoxia-ischaemia was neuroprotective in this perinatal asphyxia model.

PMID- 23171225
TI  - Dual origin, development, and fate of bovine pancreatic islets.
AB  - Endocrine cells are evident at an early stage in bovine pancreatic development
      when the pancreas still consists of primitive epithelial cords. At this stage,
      the endocrine cells are interspersed between the precursor cells destined to form
      the ductulo-acinar trees of later exocrine lobules. We here demonstrate that, in
      bovine fetuses of crown rump length >= 11 cm, the endocrine cells become
      increasingly segregated from the developing exocrine pancreas by assembly into
      two units that differ in histogenesis, architecture, and fate. Small numbers of
      'perilobular giant islets' are distinguishable from larger numbers of
      'intralobular small islets'. The two types of islets arise in parallel from the
      ends of the ductal tree. Aside from differences in number, location, and size,
      the giant and small islets differ in cellular composition (predominantly insulin
      synthesising cells vs. mixtures of endocrine cells), morphology (epithelial
      trabeculae with gyriform and rosette-like appearance vs. compact circular
      arrangements of endocrine cells), and in their relationships to intrapancreatic
      ganglia and nerves. A further difference becomes apparent during the antenatal
      period; while the 'interlobular small islets' persist in the pancreata of calves
      and adult cattle, the perilobular giant islets are subject to regression,
      characterised by involution of the parenchyma, extensive haemorrhage, leukocyte
      infiltration (myeloid and T-cells) and progressive fibrotic replacement. In
      conclusion, epithelial precursor cells of the ductolo-acinar tree may give rise
      to populations of pancreatic islets with different histomorphology, cellular
      composition and fates. This should be taken into account when using these cells
      for the generation of pancreatic islets for transplantation therapy.

PMID- 23171226
TI  - A rapid assessment of the quality of neonatal healthcare in Kilimanjaro region,
      northeast Tanzania.
AB  - BACKGROUND: While child mortality is declining in Africa there has been no
      evidence of a comparable reduction in neonatal mortality. The quality of
      inpatient neonatal care is likely a contributing factor but data from resource
      limited settings are few. The objective of this study was to assess the quality
      of neonatal care in the district hospitals of the Kilimanjaro region of Tanzania.
      METHODS: Clinical records were reviewed for ill or premature neonates admitted to
      13 inpatient health facilities in the Kilimanjaro region; staffing and equipment
      levels were also assessed. RESULTS: Among the 82 neonates reviewed, key health
      information was missing from a substantial proportion of records: on maternal
      antenatal cards, blood group was recorded for 52 (63.4%) mothers, Rhesus (Rh)
      factor for 39 (47.6%), VDRL for 59 (71.9%) and HIV status for 77 (93.1%). From
      neonatal clinical records, heart rate was recorded for3 (3.7%) neonates,
      respiratory rate in 14, (17.1%) and temperature in 33 (40.2%). None of 13
      facilities had a functioning premature unit despite calculated gestational age
      <36 weeks in 45.6% of evaluated neonates. Intravenous fluids and oxygen were
      available in 9 out of 13 of facilities, while antibiotics and essential basic
      equipment were available in more than two thirds. Medication dosing errors were
      common; under-dosage for ampicillin, gentamicin and cloxacillin was found in
      44.0%, 37.9% and 50% of cases, respectively, while over-dosage was found in
      20.0%, 24.2% and 19.9%, respectively. Physician or assistant physician staffing
      levels by the WHO indicator levels (WISN) were generally low. CONCLUSION: Key
      aspects of neonatal care were found to be poorly documented or incorrectly
      implemented in this appraisal of neonatal care in Kilimanjaro. Efforts towards
      quality assurance and enhanced motivation of staff may improve outcomes for this
      vulnerable group.

PMID- 23171227
TI  - Weight bias among UK trainee dietitians, doctors, nurses and nutritionists.
AB  - BACKGROUND: Trainee dietitians, nutritionists, nurses and doctors will direct the
      future of obesity treatment and prevention. To do so effectively, they must be
      willing and able to engage empathically with overweight and obese people. The
      present study aimed to assess weight bias among UK trainee healthcare
      professionals and to investigate the factors predicting weight bias, both static
      and potentially modifiable. METHODS: A self-completed questionnaire collected
      data on demographics, weight and height, the Fat Phobia Scale (F-scale), and the
      Beliefs about Obese People (BOAP) scale from 1130 students. RESULTS: Overall,
      participants demonstrated significant levels of fat phobia [F-scale score mean
      (SD) = 3.8 (0.5)]. Only 1.4% of participants could be said to have expressed
      'positive or neutral attitudes' (i.e. achieved a F-scale score <= 2.5).
      Hierarchical multiple regression revealed that lower fat phobia (as measured by
      the F-scale) was uniquely predicted by a higher self-reported body mass index,
      being on the Nursing BSc course and a stronger perception that obesity is not
      under a person's control (as measured by the BOAP scale). CONCLUSIONS: There are
      unacceptable levels of weight bias among UK students training to become nurses,
      doctors, nutritionists and dietitians. The results of the present study suggest
      that a promising approach for future interventions would be the provision of
      balanced education about the controllability of obesity, focusing upon genetic
      and environmental factors, as well as diet and exercise.

PMID- 23171229
TI  - The impact of alcohol on Alzheimer's disease: a systematic review.
AB  - Currently, there is discrepancy regarding alcohol's impact on Alzheimer's disease
      (AD). Consequently, the purpose of this systematic review was to determine
      whether alcohol serves as a protective agent against the development of AD, as
      well as whether protective effects are influenced by quantity and/or frequency of
      drinking. Adapted versions of the Matrix Method and PRISMA guidelines were used
      in order to identify, organize, and synthesize relevant research. Overall, there
      is no consensus regarding alcohol's impact on AD. Specifically, seven articles
      suggested drinking alcohol decreases the risk of AD, three studies found drinking
      led to an increased risk of AD, and yet another nine reported alcohol had no
      impact on AD. Validity and consistency of both alcohol and AD measures across
      studies represents a severe limitation. Prior to the development of standards
      and/or clinical recommendations, more investigations into the association between
      alcohol and AD are necessary. Considering the current evidence base, alcohol
      should not be used as a means to decrease risk of developing AD.

PMID- 23171230
TI  - Fabrication of highly-aligned, conductive, and strong graphene papers using
      ultralarge graphene oxide sheets.
AB  - This study demonstrates that large-size graphene oxide (GO) sheets can impart a
      tremendous positive impact on self-alignment, electrical conductivity, and
      mechanical properties of graphene papers. There is a remarkable, more than 3-fold
      improvement in electrical conductivity of the papers made from ultralarge GO
      sheets (with an average area of 272.2 MUm(2)) compared to that of the small GO
      counterpart (with an average area of 1.1 MUm(2)). The corresponding improvements
      in Young's modulus and tensile strength are equally notable, namely 320% and
      280%, respectively. These improvements of bulk properties due to the large GO
      sheets are correlated to multiscale elemental and structural characteristics of
      GO sheets, such as the content of carboxyl groups on the GO edge, C/O ratio and
      Raman D/G-band intensity ratio of GO on the molecular-scale, and the degree of
      dispersion and stacking behavior of GO sheets on the microscale. The graphene
      papers made from larger GO sheets exhibit a closer-stacked structure and better
      alignment as confirmed by the fast Fourier transform analysis, to the benefits of
      their electrical conductivity and mechanical properties. The molecular dynamics
      simulation further elucidates that the enhanced intersheet interactions between
      large GO sheets play a key role in improving the Young's modulus of GO papers.
      The implication is that the said properties can be further improved by enhancing
      the intersheet stress transfer and electrical conduction especially through the
      thickness direction.

PMID- 23171228
TI  - The protein interaction network of a taxis signal transduction system in a
      halophilic archaeon.
AB  - BACKGROUND: The taxis signaling system of the extreme halophilic archaeon
      Halobacterium (Hbt.) salinarum differs in several aspects from its model
      bacterial counterparts Escherichia coli and Bacillus subtilis. We studied the
      protein interactions in the Hbt. salinarum taxis signaling system to gain an
      understanding of its structure, to gain knowledge about its known components and
      to search for new members. RESULTS: The interaction analysis revealed that the
      core signaling proteins are involved in different protein complexes and our data
      provide evidence for dynamic interchanges between them. Fifteen of the eighteen
      taxis receptors (halobacterial transducers, Htrs) can be assigned to four
      different groups depending on their interactions with the core signaling
      proteins. Only one of these groups, which contains six of the eight Htrs with
      known signals, shows the composition expected for signaling complexes (receptor,
      kinase CheA, adaptor CheW, response regulator CheY). From the two Hbt. salinarum
      CheW proteins, only CheW1 is engaged in signaling complexes with Htrs and CheA,
      whereas CheW2 interacts with Htrs but not with CheA. CheY connects the core
      signaling structure to a subnetwork consisting of the two CheF proteins (which
      build a link to the flagellar apparatus), CheD (the hub of the subnetwork), two
      CheC complexes and the receptor methylesterase CheB. CONCLUSIONS: Based on our
      findings, we propose two hypotheses. First, Hbt. salinarum might have the
      capability to dynamically adjust the impact of certain Htrs or Htr clusters
      depending on its current needs or environmental conditions. Secondly, we propose
      a hypothetical feedback loop from the response regulator to Htr methylation made
      from the CheC proteins, CheD and CheB, which might contribute to adaptation
      analogous to the CheC/CheD system of B. subtilis.

PMID- 23171231
TI  - Understanding the independent influence of duty and achievement striving when
      predicting the relationship between conscientiousness and organizational cultural
      profiles and helping behaviors.
AB  - The theory that 2 facets of the factor conscientiousness, duty and achievement
      striving, are related to self- or other-centered motives, is supported in 2
      studies. In Study 1 (N = 204 undergraduates), the self-centered facet of
      achievement striving was found to be the most important predictor of attraction
      toward organizational cultures that were outcome-based, aggressive, and
      emphasized rewards. Achievement strivers were less attracted to supportive and
      decisive organizations. In Study 2 (N = 189 part-time MBA students) the other
      centered facet of duty was found to be predictive of helping behaviors.
      Theoretical and practical implications are discussed.

PMID- 23171232
TI  - Emission and transport of 1,3-dichloropropene and chloropicrin in a large field
      tarped with VaporSafe TIF.
AB  - Tarping fumigated fields with low permeability films such as commercial Totally
      Impermeable Film (TIF) can significantly reduce emissions, but it can also
      increase fumigant residence time in the soil such that extended tarp-covering
      durations may be required to address potential exposure risks during tarp-cutting
      and removal. In an effort to develop safe practices for using TIF, a large field
      study was conducted in the San Joaquin Valley of California. Comprehensive data
      on emissions (measured with dynamic flux chambers), fate, and transport of 1,3
      dichloropropene and chloropicrin were collected in a 3.3 ha field fumigated with
      Pic-Clor 60 via broadcast shank application. Low emission flux (below 15 MUg m(
      2) s(-1)) was observed from the tarped field throughout the tarp-covering period
      of 16 days with total emission loss of <8% of total applied for both chemicals.
      Although substantially higher flux was measured at tarp edges (up to 440 MUg m(
      2) s(-1)), the flux was reduced to below 0.5 MUg m(-2) s(-1) beyond 2 m of tarp
      edge where total mass loss was estimated to be <= 1% of total applied to the
      field. Emission flux increased following tarp-cutting, but was much lower
      compared to 5 or 6 d tarp-covering periods determined in other fields. This study
      demonstrated the ability of TIF to significantly reduce fumigant emissions with
      supporting data on fumigant movement in soil. Proper management on use of the
      tarp, such as extending tarp-covering period, can reduce negative impact on the
      environment and help maintain the beneficial use of soil fumigants for
      agricultural productions.

PMID- 23171233
TI  - Post-stroke subjective cognitive impairment is associated with acute lacunar
      infarcts in the basal ganglia.
AB  - BACKGROUND AND PURPOSE: While recent studies have examined neuroimaging
      correlates of post-stroke mild cognitive impairment (MCI), no studies have
      examined neuroimaging correlates of post-stroke subjective cognitive impairment
      (SCI). METHODS: Consecutive patients with magnetic resonance imaging-confirmed
      acute lacunar strokes at a tertiary institute were recruited for this cross
      sectional study. All patients underwent cognitive testing, and those with MCI
      were excluded from these analyses. Two independent neuroradiologists ascertained
      data on the number and location of any infarcts, as well as the degree of white
      matter hyperintensities. Multivariate logistic regression analyses were performed
      to study the association between neuroimaging markers and SCI. Only variables
      that were significant in the univariate stage and clinically relevant potential
      confounders were included in multivariable analyses. RESULTS: Of 145 patients
      evaluated, 48 patients with MCI were excluded from the study. Of the remaining 97
      patients, 30 patients had SCI. In multivariable analyses, only mini-mental state
      examination (OR 0.61; CI 0.38-0.98) and basal ganglia infarcts (OR 8.19; CI 1.18
      56.6) were significant predictors of SCI. CONCLUSION: In patients with acute
      lacunar strokes, we find that basal ganglia infarcts are associated with SCI. As
      the basal ganglia have been previously shown to be involved with learning of
      tasks, we hypothesize that infarcts in basal ganglia may affect learning speeds
      thereby contributing to the development of SCI. Larger studies are needed to
      confirm these results.

PMID- 23171234
TI  - False positives and false negatives: is the answer relatively simple?

PMID- 23171235
TI  - Highly enhanced exciton recombination rate by strong electron-phonon coupling in
      single ZnTe nanobelt.
AB  - Electron-phonon coupling plays a key role in a variety of elemental excitations
      and their interactions in semiconductor nanostructures. Here we demonstrate that
      the relaxation rate of free excitons in a single ZnTe nanobelt (NB) is
      considerably enhanced via a nonthermalized hot-exciton emission process as a
      result of an ultrastrong electron-phonon coupling. Using time-resolved
      photoluminescence (PL) spectroscopy and resonant Raman spectroscopy (RRS), we
      present a comprehensive study on the identification and the dynamics of
      free/bound exciton recombination and the electron-phonon interactions in
      crystalline ZnTe NBs. Up to tenth-order longitudinal optical (LO) phonons are
      observed in Raman spectroscopy, indicating an ultrastrong electron-phonon
      coupling strength. Temperature-dependent PL and RRS spectra suggest that electron
      phonon coupling is mainly contributed from Light hole (LH) free excitons. With
      the presence of hot-exciton emission, two time constants (~80 and ~18 ps) are
      found in photoluminescence decay curves, which are much faster than those in many
      typical semiconductor nanostructures. Finally we prove that under high excitation
      power amplified spontaneous emission (ASE) originating from the electron-hole
      plasma occurs, thereby opening another radiative decay channel with an ultrashort
      lifetime of few picoseconds.

PMID- 23171236
TI  - The variety of photorespiratory phenotypes - employing the current status for
      future research directions on photorespiration.
AB  - Mutations of genes encoding for proteins within the photorespiratory core cycle
      and associated processes are characterised by lethality under normal air but
      viability under elevated CO2 conditions. This feature has been described as 'the
      photorespiratory phenotype' and assumed to be distinctly equal for all of these
      mutants. In recent years a broad collection of photorespiratory mutants has been
      isolated, which has allowed a comparative analysis. Distinct phenotypic features
      were observed when Arabidopsis thaliana mutants defective in photorespiratory
      enzymes were compared, and during shifts from elevated to ambient CO2 conditions.
      The exact reasons for the mutant-specific photorespiratory phenotypes are mostly
      unknown, but they indicate even more plasticity of photorespiratory metabolism.
      Moreover, a growing body of evidence was obtained that mutant features could be
      modulated by alterations of several factors, such as CO2 :O2 ratios, photoperiod,
      light intensity, organic carbon supply and pathogens. Hence, systematic analyses
      of the responses to these factors appear to be crucial to unravel mechanisms how
      photorespiration adapts and interacts with the whole cellular metabolism. Here we
      review current knowledge regarding photorespiratory mutants and propose a new
      level of phenotypic sub-classification. Finally, we present further questions
      that should be addressed in the field of photorespiration.

PMID- 23171237
TI  - Sociodemographic and clinical features of gender identity disorder: an Italian
      multicentric evaluation.
AB  - INTRODUCTION: Male to female (MtFs) and female to male (FtMs) subjects with
      gender identity disorder (GID) seem to differ with regard to some
      sociodemographic and clinical features. Currently, no descriptive studies
      focusing on MtFs and FtMs attending an Italian clinic are available. AIM: To
      describe the sociodemographic characteristics of a GID population seeking
      assistance for gender transition and to assess possible differences in those
      features between MtFs and FtMs. METHODS: A consecutive series of 198 patients was
      evaluated for gender dysphoria from July 2008 to May 2011 in four dedicated
      centers. A total of 140 subjects (mean age 32.6 +/- 9.0 years old) meeting the
      criteria for GID, with their informed consent and without genital reassignment
      surgery having already been performed, were considered (92 MtFs and 48 FtMs).
      Diagnosis was based on formal psychiatric classification criteria. MAIN OUTCOME
      MEASURES: Medical history and sociodemographic characteristics were investigated.
      Subjects were asked to complete the Body Uneasiness Test (a self-rating scale
      exploring different areas of body-related psychopathology), Symptom Checklist-90
      Revised (a self-rating scale to measure psychological state), and the Bem Sex
      Role Inventory (a self-rating scale to evaluate gender role). The presence of
      psychiatric comorbidities was evaluated using the Structured Clinical Interviews
      for Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text
      Revision (DSM-IV-TR) (SCID I and SCID II). RESULTS: Several significant
      differences were found between MtFs and FtMs regarding lifestyle and
      sociodemographic factors and in psychometric test scores. No differences were
      found in terms of psychiatric comorbidity. CONCLUSIONS: This is the first large
      study reporting the sociodemographic characteristics of a GID sample referring to
      Italian clinics, and it provides different profiles for MtFs and FtMs. In
      particular, FtMs display significantly better social functioning.

PMID- 23171238
TI  - Compounds from Sorindeia juglandifolia (Anacardiaceae) exhibit potent anti
      plasmodial activities in vitro and in vivo.
AB  - BACKGROUND: Discovering new lead compounds against malaria parasites is a crucial
      step to ensuring a sustainable global pipeline for effective anti-malarial drugs.
      As far as we know, no previous phytochemical or pharmacological investigations
      have been carried out on Sorindeia juglandifolia. This paper describes the
      results of an anti-malarial activity-driven investigation of the fruits of this
      Cameroonian plant. METHODS: Air-dried fruits were extracted by maceration using
      methanol. The extract was fractionated by flash chromatography followed by column
      chromatography over silica gel, eluting with gradients of hexane-ethyl acetate
      mixtures. Resulting fractions and compounds were tested in vitro against the
      Plasmodium falciparum chloroquine-resistant strain W2, against field isolates of
      P. falciparum, and against the P. falciparum recombinant cysteine protease
      falcipain-2. Promising fractions were assessed for acute toxicity after oral
      administration in mice. One of the promising isolated compounds was assessed in
      vivo against the rodent malaria parasite Plasmodium berghei. RESULTS: The main
      end-products of the activity-guided fractionation were 2,3,6-trihydroxy benzoic
      acid (1) and 2,3,6-trihydroxy methyl benzoate (2). Overall, nine fractions tested
      against P. falciparum W2 and falcipain-2 were active, with IC50 values of 2.3
      11.6 MUg/ml for W2, and 1.1-21.9 MUg/ml for falcipain-2. Purified compounds (1)
      and (2) also showed inhibitory effects against P. falciparum W2 (IC50s 16.5 MUM
      and 13.0 MUM) and falcipain-2 (IC50s 35.4 and 6.1 MUM). In studies of P.
      falciparum isolates from Cameroon, the plant fractions demonstrated IC50 values
      of 0.14-19.4 MUg/ml and compounds (1) and (2) values of 6.3 and 36.1 MUM. In vivo
      assessment of compound (1) showed activity against P. berghei strain B, with mean
      parasitaemia suppressive dose and curative dose of 44.9 mg/kg and 42.2 mg/kg,
      respectively. Active fractions were found to be safe in mice after oral
      administration of 7 g/kg body weight. CONCLUSIONS: Fractions of Sorindeia
      juglandifolia and two compounds isolated from these fractions were active against
      cultured malaria parasites, the P. falciparum protease falcipain-2, and in a
      rodent malaria model. These results suggest that further investigation of the
      anti-malarial activities of natural products from S. juglandifolia will be
      appropriate.

PMID- 23171240
TI  - Structural, optical, and electrochemical properties of three-dimensional push
      pull corannulenes.
AB  - Electrochemically active corannulene derivatives with various numbers of electron
      donating 4-(N,N-dimethylamino)phenylethynyl (1-4) or electron-withdrawing
      cyanobutadienyl peripheral substitutents (5-8) were prepared. The latter
      derivatives resulted from formal [2 + 2] cycloaddition of cyanoolefins to 1-4
      followed by retro-electrocyclization. Conformational properties were examined by
      variable-temperature NMR and X-ray diffraction and opto-electronic properties by
      electronic absorption/emission spectra and electrochemical measurements; these
      analyses were corroborated by dispersion-corrected density functional
      calculations at the level of B97-D/def2-TZVPP. In CH(2)Cl(2), 1-4 exhibit
      intramolecular charge-transfer (ICT) absorptions at 350-550 nm and green
      (lambda(em) ~ 540 nm) or orange (600 nm) fluorescence with high quantum yields
      (56-98%) and are more readily reduced than corannulene by up to 490 mV. The
      variation of optical gap and redox potentials of 1-4 does not correlate with the
      number of substituents. Cyanobutadienyl corannulenes 5-8 show red-shifted ICT
      absorptions with end-absorptions approaching 800 nm. Intersubstituent
      interactions lead to distortions of the corannulene core and lower the molecular
      symmetry. NMR, X-ray, and computational studies on 5 and 8 with one
      cyanobutadienyl substituent suggested the formation of intermolecular corannulene
      dimers. Bowl-inversion barriers around DeltaG(?) = 10-11 kcal/mol were determined
      for these two molecules.

PMID- 23171241
TI  - Universally dispersible carbon nanotubes.
AB  - We show that supramolecular chemistry provides a convenient tool to prepare
      carbone nanotubes (CNTs) that can be dispersed in solvents of any chemical
      nature, easily recovered and redispersed. Thymine-modified CNTs (CNT-Thy) can be
      dispersed in solution in the presence of diaminotriazine (DAT) end-functionalized
      polymers, through supramolecular Thy/DAT association. DAT-polymer chains are
      selected according to the solvent chemical nature: polystyrene (PS) for
      hydrophobic/low polarity solvents and a propylene oxide/ethylene oxide copolymer
      (predominantly propylene oxide based, PPO/PEO) for polar solvents or water. Long
      term stable supramolecular CNT dispersions are reversibly aggregated by adding a
      few droplets of a selective dissociating agent of the Thy/DAT association (DMSO).
      CNT-Thy, simply recycled by centrifugation or filtration, can be redispersed in
      another solvent in presence of a suitable soluble DAT-polymer. Dispersion and
      aggregation can also be switched on and off by choosing a polymer for which a
      given solvent is close to Theta-conditions, e.g., PS in cyclohexane or PPO/PEO in
      water.

PMID- 23171239
TI  - Adult siblings with homozygous G6PC3 mutations expand our understanding of the
      severe congenital neutropenia type 4 (SCN4) phenotype.
AB  - BACKGROUND: Severe congenital neutropenia type 4 (SCN4) is an autosomal recessive
      disorder caused by mutations in the third subunit of the enzyme glucose-6
      phosphatase (G6PC3). Its core features are congenital neutropenia and a prominent
      venous skin pattern, and affected individuals have variable birth defects.
      Oculocutaneous albinism type 4 (OCA4) is caused by autosomal recessive mutations
      in SLC45A2. METHODS: We report a sister and brother from Newfoundland, Canada
      with complex phenotypes. The sister was previously reported by Cullinane et al.,
      2011. We performed homozygosity mapping, next generation sequencing and
      conventional Sanger sequencing to identify mutations that cause the phenotype in
      this family. We have also summarized clinical data from 49 previously reported
      SCN4 cases with overlapping phenotypes and interpret the medical histories of
      these siblings in the context of the literature. RESULTS: The siblings' phenotype
      is due in part to a homozygous mutation in G6PC3, [c.829C > T, p.Gln277X]. Their
      ages are 38 and 37 years respectively and they are the oldest SCN4 patients
      published to date. Both presented with congenital neutropenia and later developed
      Crohn disease. We suggest that the latter is a previously unrecognized SCN4
      manifestation and that not all affected individuals have an intellectual
      disability. The sister also has a homozygous mutation in SLC45A2, which explains
      her severe oculocutaneous hypopigmentation. Her brother carried one SLC45A2
      mutation and was diagnosed with "partial OCA" in childhood. CONCLUSIONS: This
      family highlights that apparently novel syndromes can in fact be caused by two
      known autosomal recessive disorders.

PMID- 23171242
TI  - Response of adsorbed polyelectrolyte monolayers to changes in solution
      composition.
AB  - Reflectometry and quartz crystal microbalance are used to study the response of
      adsorbed polyelectrolyte monolayers to solutions of variable composition. These
      techniques respectively yield the dry and wet masses of the adsorbed layer, and
      by combing these results, one obtains the water content and the thickness of the
      polyelectrolyte films. The systems investigated are films of adsorbed poly(allyl
      amine) (PAH) and poly-L-lysine (PLL) on silica and films of poly(styrene
      sulfonate) (PSS) on amino-functionalized silica. When such films are adsorbed
      from concentrated polyelectrolyte solutions containing high levels of salt, they
      are found to swell reversibly up to a factor of 2 when incubated in solutions of
      low salt. This swelling is attributed to the strengthening of repulsive
      electrostatic interactions between the adsorbed polyelectrolyte chains. PAH films
      may also swell upon decrease of pH, and collapse upon a pH increase. This
      transition shows a marked hysteresis and can be rationalized by the competition
      of electrostatic repulsions between the chains and their attraction to the
      surface. The presently observed swelling phenomena are caused by a collective
      process driven by the electrostatic repulsion between the densely adsorbed
      polyelectrolyte chains. Such responsive layers are only obtained by adsorption
      from high polyelectrolyte and salt concentrations. Layers absorbed at low
      polyelectrolyte and salt concentrations show only minor swelling effects, since
      the adsorbed polyelectrolytes layers are dilute and the adsorbed polyelectrolyte
      chains interact only weakly.

PMID- 23171244
TI  - Caries preventive efficacy of silver diammine fluoride (SDF) and ART sealants in
      a school-based daily fluoride toothbrushing program in the Philippines.
AB  - BACKGROUND: Occlusal surfaces of erupting and newly erupted permanent molars are
      particularly susceptible to caries.The objective of the study was to assess and
      compare the effect of a single application of 38% SDF with ART sealants and no
      treatment in preventing dentinal (D3) caries lesions on occlusal surfaces of
      permanent first molars of school children who participated in a daily school
      based toothbrushing program with fluoride toothpaste. METHODS: The prospective
      community clinical trial in the Philippines was conducted over a period of 18
      months and included 704 six- to eight-year-old school children in eight public
      elementary schools with a daily school-based fluoride toothpaste brushing
      program. Children were randomly assigned for SDF application or ART sealant
      treatment. Children from two of the eight schools did not receive SDF or ART
      sealant treatment and served as controls. SDF or ART sealant treatment was
      applied on sound occlusal surfaces of permanent first molars. Surfaces that were
      originally defined as sound at baseline but which changed to dentinal (D3) caries
      lesions were defined as surfaces with new caries (caries increment). Non
      compliance to the daily toothbrushing program in three schools offered the
      opportunity to analyze the caries preventive effect of SDF and sealants
      separately in fluoride toothpaste brushing and in non-toothbrushing children.
      RESULTS: In the brushing group, caries increment in the SDF treatment group was
      comparable with the non-treatment group but caries increment in the sealant group
      was lower than in the non-treatment group with a statistically significant lower
      hazard ratio of 0.12 (0.02-0.61). In the non-brushing group, caries increment in
      the SDF treatment group and the sealant group was lower than the non-treatment
      group but the hazard ratio was only statistically significant for the sealant
      group (HR 0.33; 0.20-0.54). Caries increment was lower in toothbrushing children
      than in non-toothbrushing children. Hazard ratios reached statistical
      significance for the non-treated children (HR 0.43; 0.21-0.87) and the sealant
      treated children (HR 0.15; 0.03-0.072). CONCLUSIONS: A one-time application of
      38% SDF on the occlusal surfaces of permanent first molars of six- to eight-year
      old children is not an effective method to prevent dentinal (D3) caries lesions.
      ART sealants significantly reduced the onset of caries over a period of 18
      months. TRIAL REGISTRATION NUMBER: German Clinical Trial Register DRKS00003427.

PMID- 23171247
TI  - Age-related pupillary miosis should be considered in pseudophakic circadian
      photoreception analysis - authors' reply.

PMID- 23171246
TI  - Does eating slowly influence appetite and energy intake when water intake is
      controlled?
AB  - BACKGROUND: Slow eating has been associated with enhanced satiation, but also
      with increased water intake. Therefore, the role of water ingestion in regard to
      eating rate needs to be discerned. This study examined the influence of eating
      rate on appetite regulation and energy intake when water intake is controlled.
      METHODS: In a randomized design, slow and fast eating rates were compared on two
      occasions, in 30 women (22.7+/-1.2 y; BMI=22.4+/-0.4 kg/m2) who consumed an ad
      libitum mixed-macronutrient lunch with water (300 mL). Satiation was examined as
      the main outcome by measuring energy intake during meals. At designated times,
      subjects rated hunger, satiety, desire-to-eat, thirst, and meal palatability on
      visual analogue scales. Paired t-tests were used to compare hypothesis-driven
      outcomes. Appetite ratings were compared across time points and conditions by
      repeated measures analysis of variance (ANOVA) using a within-subject model.
      RESULTS: Energy intake and appetite ratings did not differ between conditions at
      meal completion. However, subjects rated less hunger and tended to rate lower
      desire-to-eat and greater satiety at 1 hour following the slow condition.
      CONCLUSIONS: Results tend to support a role of slow eating on decreased hunger
      and higher inter-meal satiety when water intake is controlled. However, the lack
      of significant differences in energy intake under these conditions indicates that
      water intake may account for the effects of eating rate on appetite regulation.

PMID- 23171245
TI  - Identification, characterization and distribution of transposable elements in the
      flax (Linum usitatissimum L.) genome.
AB  - BACKGROUND: Flax (Linum usitatissimum L.) is an important crop for the production
      of bioproducts derived from its seed and stem fiber. Transposable elements (TEs)
      are widespread in plant genomes and are a key component of their evolution. The
      availability of a genome assembly of flax (Linum usitatissimum) affords new
      opportunities to explore the diversity of TEs and their relationship to genes and
      gene expression. RESULTS: Four de novo repeat identification algorithms (PILER,
      RepeatScout, LTR_finder and LTR_STRUC) were applied to the flax genome assembly.
      The resulting library of flax repeats was combined with the RepBase Viridiplantae
      division and used with RepeatMasker to identify TEs coverage in the genome. LTR
      retrotransposons were the most abundant TEs (17.2% genome coverage), followed by
      Long Interspersed Nuclear Element (LINE) retrotransposons (2.10%) and Mutator DNA
      transposons (1.99%). Comparison of putative flax TEs to flax transcript databases
      indicated that TEs are not highly expressed in flax. However, the presence of
      recent insertions, defined by 100% intra-element LTR similarity, provided
      evidence for recent TE activity. Spatial analysis showed TE-rich regions, gene
      rich regions as well as regions with similar genes and TE density. Monte Carlo
      simulations for the 71 largest scaffolds (>= 1 Mb each) did not show any regional
      differences in the frequency of TE overlap with gene coding sequences. However,
      differences between TE superfamilies were found in their proximity to genes.
      Genes within TE-rich regions also appeared to have lower transcript expression,
      based on EST abundance. When LTR elements were compared, Copia showed more
      diversity, recent insertions and conserved domains than the Gypsy, demonstrating
      their importance in genome evolution. CONCLUSIONS: The calculated 23.06% TE
      coverage of the flax WGS assembly is at the low end of the range of TE coverages
      reported in other eudicots, although this estimate does not include TEs likely
      found in unassembled repetitive regions of the genome. Since enrichment for TEs
      in genomic regions was associated with reduced expression of neighbouring genes,
      and many members of the Copia LTR superfamily are inserted close to coding
      regions, we suggest Copia elements have a greater influence on recent flax genome
      evolution while Gypsy elements have become residual and highly mutated.

PMID- 23171248
TI  - Altered cortical and subcortical local coherence in obstructive sleep apnea: a
      functional magnetic resonance imaging study.
AB  - Obstructive sleep apnea (OSA) syndrome is the most common sleep-related breathing
      disorder, characterized by excessive snoring and repetitive apneas and arousals,
      which leads to fragmented sleep and, most importantly, to intermittent nocturnal
      hypoxaemia during apneas. Considering previous studies about morphovolumetric
      alterations in sleep apnea, in this study we aimed to investigate for the first
      time the functional connectivity profile of OSA patients and age-gender-matched
      healthy controls, using resting-state functional magnetic resonance imaging
      (fMRI). Twenty severe OSA patients (mean age 43.2 +/- 8 years; mean apnea
      hypopnea index, 36.3 h(-1) ) and 20 non-apneic age-gender-body mass index (BMI)
      matched controls underwent fMRI and polysomnographic (PSG) registration, as well
      as mood and sleepiness evaluation. Cerebro-cerebellar regional homogeneity (ReHo)
      values were calculated from fMRI acquisition, in order to identify pathology
      related alterations in the local coherence of low-frequency signal (<0.1 Hz).
      Multivariate pattern classification was also performed using ReHo values as
      features. We found a significant pattern of cortical and subcortical abnormal
      local connectivity in OSA patients, suggesting an overall rearrangement of
      hemispheric connectivity balance, with a decrease of local coherence observed in
      right temporal, parietal and frontal lobe regions. Moreover, an increase in
      bilateral thalamic and somatosensory/motor cortices coherence have been found, a
      finding due possibly to an aberrant adaptation to incomplete sleep-wake
      transitions during nocturnal apneic episodes, induced by repetitive choke
      sensation and physical efforts attempting to restore breathing. Different
      hemispheric roles into sleep processes and a possible thalamus key role in OSA
      neurophysiopathology are intriguing issues that future studies should attempt to
      clarify.

PMID- 23171249
TI  - The TOL network of Pseudomonas putida mt-2 processes multiple environmental
      inputs into a narrow response space.
AB  - The TOL system encoded by plasmid pWW0 of Pseudomonas putida mt-2 is able to
      sense a large number of both exogenous and endogenous signals as inputs for the
      genetic and metabolic circuit that determines the biodegradation of m-xylene.
      However, whether the enormous combinatorial space of inputs is translated into an
      equally variable response landscape or is processed into very few outcomes
      remains unclear. To address this question, we set out to define the number of
      states that can be obtained by a network of a given set of genes under the
      control of a specified regulatory circuit that is exposed to all possible
      combinations of inputs. To this end, the TOL network and its regulatory wiring
      were formalized as a synchronous logic Boolean circuit that had 10 signals (i.e.
      pathway substrates, temperature, sugars, amino acids, metabolic regimes and
      global regulators) as possible inputs. The analysis of the attractors of the
      circuit using a satisfiability (SAT) algorithm revealed that only eight
      transcriptional states are reached in response to the 1024 possible combinations
      of stimuli. The experimental validation resulted in a refinement of the model
      through the addition of a previously unknown interaction that controls the meta
      catabolic pathway. The full induction of the two xyl operons occurred with only
      1.6% of the input combinations, which suggests that the architecture of the
      network allows the expression of the xyl genes only under a very narrow range of
      conditions. These data not only explain much of the unusual layout of the TOL
      circuit but also strengthen the view of the regulatory circuits of environmental
      bacteria as digital decision-making devices.

PMID- 23171251
TI  - Henry Walton.

PMID- 23171252
TI  - Talking about power in medical education.

PMID- 23171253
TI  - Power, professional identity and the doctor who can heal all ailments.

PMID- 23171254
TI  - Sociomateriality matters to family practitioners as supervisors.

PMID- 23171255
TI  - Let's talk about thinking.

PMID- 23171256
TI  - A call to address the curricular provision of emotional support in the event of
      medical errors and adverse events.

PMID- 23171257
TI  - Power, leadership and transformation: the doctor's potential for influence.
AB  - CONTEXT: Power and leadership are concepts that are linked. Both are studied too
      infrequently in medical and health care settings, given the responsibilities and
      opportunities doctors and other health care personnel have to exert leadership
      and power appropriately to foster patient-centred and health care organisational
      goals. METHODS: This paper reviews Raven's concept of power, clarifies the bases
      of power that are available to doctors in different roles and provides
      illustrations of the application of the bases of power in medical practice. The
      relationship between power and leadership is explored, with an emphasis on how
      power and leadership are linked through the personal characteristics and
      competencies of the leader. RESULTS:   Transformational leadership illustrates
      the incorporation and elaboration of power strategies into a principles-driven,
      relationship-oriented and empirically grounded form of leadership. Illustrations
      of the appropriate and inappropriate use of power and leadership in health care
      settings are provided. CONCLUSIONS: The study of power, the study of leadership
      and their linkage should be incorporated to a greater degree into medical
      education at all levels. Strategies to achieve this end are suggested.

PMID- 23171258
TI  - General practitioners as supervisors in postgraduate clinical education: an
      integrative review.
AB  - CONTEXT: General practice supervisors are said to serve as the cornerstones of
      general practice postgraduate education and therefore it is important to clearly
      define their roles and what makes them effective. The commonly used definition of
      a supervisor is not primarily based on general practice and does not cover
      aspects predicted to be important according to work-based learning theory.
      METHODS: We searched for papers published between 1991 and 2011 inclusive,
      categorised them according to whether they provided empirical evidence,
      descriptions or recommendations, open-coded the empirical evidence, and used the
      resulting coding scheme as an analytic framework within which to present a
      narrative summary of findings. RESULTS: Recommendations and descriptions far
      outweighed empirical evidence, which showed how supervisors intertwined clinical
      and educational activities and formed educational alliances with resident doctors
      that provided a foundation for learning. Residents needed a balance of challenge,
      usually provided by patients, and support, provided by supervisors. Supervisors
      established learning environments, assessed residents' learning needs,
      facilitated learning, monitored the content and process of learning and the well
      being of residents, and summarised learning in ways that turned 'know that' into
      'know how'. CONCLUSIONS: General practice must be expert in ensuring patients are
      well cared for 'by proxy' and in giving residents just the right amount of
      support they need to face the challenges posed by those patients. As general
      practice responds to contemporary clinical demands and rising numbers of
      undergraduate medical students, it is essential that the ability of general
      practice supervisors to develop and sustain supportive supervisory relationships
      with residents is preserved.

PMID- 23171259
TI  - Rethinking clinical reasoning: time for a dialogical turn.
AB  - CONTEXT: Clinical reasoning lies at the heart of medical practice and has been
      the subject of scholarly inquiry and research for some decades. However, despite
      this, it is still poorly understood. This is largely because current theoretical
      models are limited in their explanatory power because they are based on
      particular assumptions of what constitutes clinical reasoning. DISCUSSION: A
      variety of ways of articulating and conceptualising clinical reasoning can
      provide us with richer means of understanding what is involved in clinical
      encounters. A dialogical approach to clinical reasoning is proposed. Dialogism
      provides a vocabulary that encourages us to integrate insights from different
      frameworks in ways that combine the strengths of each. Dialogism also puts a
      focus on the complex ways in which we use language in clinical reasoning to
      generate meaning. The complexity of language includes narrative, rhetoric and
      metaphor. CONCLUSIONS: A dialogical approach does not require us to discard the
      findings of earlier theories about clinical reasoning, but provides us with a
      means of integrating what we know in ways that are more useful in the reality of
      clinical practice.

PMID- 23171260
TI  - Waking up the next morning: surgeons' emotional reactions to adverse events.
AB  - CONTEXT: The adverse patient event is an inherent component of surgical practice,
      but many surgeons are unprepared for the profound emotional responses these
      events can evoke. This study explored surgeons' reactions to adverse events and
      their impact on subsequent judgement and decision making. METHODS: Using a
      constructivist grounded theory approach, we conducted 20 semi-structured, 60
      minute interviews with surgeons across subspecialties, experience levels, and
      sexes to explore surgeons' recollections of reactions to adverse events. Further
      interviews were conducted with six general surgeons to explore more immediate
      reactions after 28 adverse events. Data coding was both inductive, developing a
      new framework based on emergent themes, and deductive, using an existing
      framework for care providers' reactions to adverse events. RESULTS: Surgeons
      expressed feeling unique and alone in the depths of their reactions to adverse
      events and consistently described four phases of response, each containing
      cognitive and emotive components, following such events. The initial phase (the
      kick) involved feelings of failure ('Am I good enough?') experienced with a
      significant physiological response. This was shortly followed by a second phase
      (the fall), during which the surgeon experienced a sense of chaos and assessed
      the extent of his or her contribution to the event ('Was it my fault?'). During
      the third phase (the recovery), the surgeon reflected on the adverse event ('What
      can I learn?') and experienced a sense of 'moving on'. In the fourth phase (the
      long-term impact), the surgeon experienced the prolonged and cumulative effects
      of these reactions on his or her own personal and professional identities.
      Surgeons also described an effect on their clinical judgement, both for the case
      in question (minimisation) and future cases (overcompensation). CONCLUSIONS:
      Surgeons progress through a series of four phases following adverse events that
      are potentially caused by or directly linked to surgeon error. The framework
      provided by this study has implications for teaching, surgeon wellness and
      surgeon error.

PMID- 23171261
TI  - Changes in residents' opportunities for experiential learning over time.
AB  - CONTEXT: Learning in the clinical environment is believed to be a crucial
      component of residency training. However, it remains unclear whether recent
      changes to postgraduate medical education, including the implementation of work
      hour limitations, have significantly impacted opportunities for experiential
      learning. Therefore, we sought to quantify opportunities to gain clinical
      experience within medical-surgical intensive care units (ICUs) over time.
      METHODS: Data on the numbers of patients admitted and invasive procedures
      performed per day between 1 July 2001 and 30 June 2010 within three academic
      medical-surgical ICUs in Calgary, Alberta, Canada were obtained from electronic
      medical records. These data were matched to resident doctor on-call schedules and
      residents' opportunities to admit patients and participate in procedures were
      calculated and compared over time using Spearman's rho. RESULTS: We found that
      over a 9-year period, the opportunities afforded to residents (n = 1156) to admit
      patients (n = 17 189) and perform procedures (n = 52 827) during ICU rotations
      decreased by 32% (p < 0.001) and 34% (p < 0.001), respectively. CONCLUSIONS: Our
      results suggest that there has been a significant decrease in residents' clinical
      experiences in the ICU over time. Further investigations to better understand
      these changes and how they may impact on performance as residents become
      independent practising doctors are warranted.

PMID- 23171262
TI  - How core competencies are taught during clinical supervision: participatory
      action research in family medicine.
AB  - OBJECTIVES: The development of professional competence is the main goal of
      residency training. Clinical supervision is the most commonly used teaching and
      learning method for the development of core competencies (CCs). The literature
      provides little information on how to encourage the learning of CCs through
      supervision. We undertook an exploratory study to describe if and how CCs were
      addressed during supervision in a family medicine residency programme. METHODS:
      We selected a participatory action research design to engage participants in
      exploring their precepting practices. Eleven volunteer faculty staff and six
      residents from a large family medicine residency programme took part in a 9-month
      process which included three focus group encounters alternating with data
      gathering during supervision. We used mostly qualitative methods for data
      collection and analysis, with thematic content analysis, triangulation of sources
      and of researchers, and member checking. RESULTS: Participants realised that they
      addressed all CCs listed as programme outcomes during clinical supervision,
      albeit implicitly and intuitively, and often unconsciously and superficially. We
      identified a series of factors that influenced the discussion of CCs: (i) CCs
      must be both known and valued; (ii) discussion of CCs occurs in a constant
      adaptation to numerous contextual factors, such as residents' characteristics;
      (iii) the teaching and learning of CCs is influenced by six challenges in the
      preceptor-resident interaction, such as residents' active engagement, and (iv)
      coherence with other curricular elements contributes to learning about CCs.
      Differences between residents' and preceptors' perspectives are discussed.
      CONCLUSIONS: This is the first descriptive study focusing on the teaching of CCs
      during clinical supervision, as experienced in a family medicine residency
      programme. Content and process issues were equally influential on the discussion
      of CCs. Our findings led to a representation of factors determining the teaching
      and learning of CCs in supervision, and suggest directions for research, for
      faculty development, and for interventions with learners.

PMID- 23171263
TI  - Development of knowledge in basic sciences: a comparison of two medical
      curricula.
AB  - CONTEXT: Basic medical sciences education differs among medicine courses,
      especially as traditional and integrated problem-based learning (PBL) curricula
      teach basic sciences in very different ways. The literature shows no clear
      differences in the performance of students of these different educational
      philosophies. The Charite Medical University of Berlin (Charite
      Universitatsmedizin Berlin) teaches both a traditional medical curriculum (TMC)
      and a PBL reformed medical curriculum (RMC). Both curricula conduct the Progress
      Test in Medicine (PTM), which examines competence in the basic and clinical
      sciences from the first to the last semester. OBJECTIVES: The aim of this study
      was to compare the development and retention of knowledge in the basic medical
      sciences between students on the traditional and reformed undergraduate medical
      curricula, respectively. METHODS: For each student and single PTM, relative
      frequencies of correct answers were computed for basic sciences items only and
      for the whole curriculum. Frequencies were averaged and grouped by semester and
      curriculum. Analyses of variance (anovas) were performed at all measurement
      points with a Bonferroni-corrected p-value at the level of p < 0.005. Eta-squared
      (eta(2)) was used to classify effect size. RESULTS: In the first three semesters,
      RMC students slightly outperform TMC students in the basic sciences, although TMC
      students receive more systematic teaching. After this, TMC students develop a
      peak of knowledge in basic sciences and overtake RMC students. The knowledge of
      TMC students then decreases over time, but despite this, they perform better in
      the final semester. Students on the RMC show constant progress throughout their
      undergraduate studies. Overall, the development of medical knowledge is
      consistent in both curricula. There is no significant difference in this outcome
      between the traditional and PBL courses. CONCLUSIONS: Progress testing as a
      longitudinal method allows us to better understand the development of knowledge
      during formal undergraduate education. The main difference between traditional
      and problem-based medical education seems to be provoked by the high-stakes
      national examination undertaken in the traditional course (the Physikum).

PMID- 23171264
TI  - Mapping as a learning strategy in health professions education: a critical
      analysis.
AB  - CONTEXT: Mapping is a means of representing knowledge in a visual network and is
      becoming more commonly used as a learning strategy in medical education. The
      assumption driving the development and use of concept mapping is that it supports
      and furthers meaningful learning. OBJECTIVES: The goal of this paper was to
      examine the effectiveness of concept mapping as a learning strategy in health
      professions education. METHODS: The authors conducted a critical analysis of
      recent literature on the use of concept mapping as a learning strategy in the
      area of health professions education. RESULTS: Among the 65 studies identified,
      63% were classified as empirical work, the majority (76%) of which used pre
      experimental designs. Only 24% of empirical studies assessed the impact of
      mapping on meaningful learning. Results of the analysis do not support the
      hypothesis that mapping per se furthers and supports meaningful learning,
      memorisation or factual recall. When documented improvements in learning were
      found, they often occurred when mapping was used in concert with other
      strategies, such as collaborative learning or instructor modelling, scaffolding
      and feedback. CONCLUSIONS: Current empirical research on mapping as a learning
      strategy presents methodological shortcomings that limit its internal and
      external validity. The results of our analysis indicate that mapping strategies
      that make use of feedback and scaffolding have beneficial effects on learning.
      Accordingly, we see a need to expand the process of reflection on the
      characteristics of representational guidance as it is provided by mapping
      techniques and tools based on field of knowledge, instructional objectives, and
      the characteristics of learners in health professions education.

PMID- 23171265
TI  - The relationship between fidelity and cost in simulation.

PMID- 23171267
TI  - Towards an open and learning safety culture.

PMID- 23171269
TI  - The functional role of the ischiopubic membrane for the mechanical loading of the
      pubis in the domestic fowl (Gallus gallus).
AB  - Soft tissues other than muscles are supposed to be of mechanical importance, yet
      they are rarely integrated into finite element models. Here, we investigate the
      functional role of the ischiopubic membrane for the loading of the pubis of the
      domestic fowl using 2D finite element analysis. For this purpose, a specimen of
      the domestic fowl was dissected and soft tissues attaching to the pubis were
      studied in great detail. Muscles were removed and measurements taken. For the 2D
      finite element model, the outline was taken from the dissected specimen. Two 2D
      finite element models were generated: one without and one with ischiopubic
      membrane. The same muscular loading based on own measurements and
      electromyographic data was applied to both models. The model without ischiopubic
      membrane shows anteroventral bending deformation of the scapus pubis, resulting
      in high compressive and tensile principal stresses at the level of ultimate bone
      stress values. The model with ischiopubic membrane shows low compressive
      principal stresses in the pubis consistent with the levels of steady state
      remodelling of bone. Based on these results, the ischiopubic membrane of the
      domestic fowl potentially establishes a physiological loading of the pubis and
      therefore might be of great mechanical significance for the loading of the bone.

PMID- 23171270
TI  - Herbivores can select for mixed defensive strategies in plants.
AB  - Resistance and tolerance are the most important defense mechanisms against
      herbivores. Initial theoretical studies considered both mechanisms functionally
      redundant, but more recent empirical studies suggest that these mechanisms may
      complement each other, favoring the presence of mixed defense patterns. However,
      the expectation of redundancy between tolerance and resistance remains
      unsupported. In this study, we tested this assumption following an ecological
      genetics field experiment in which the presence/absence of two herbivores (Lema
      daturaphila and Epitrix parvula) of Datura stramonium were manipulated. In each
      of three treatments, genotypic selection analyses were performed and selection
      patterns compared. Our results indicated that selection on resistance and
      tolerance was significantly different between the two folivores. Tolerance and
      resistance are not redundant defense strategies in D. stramonium but instead
      functioned as complementary defenses against both beetle species, favoring the
      evolution of a mixed defense strategy. Although each herbivore was selected for
      different defense strategies, the observed average tolerance and resistance were
      closer to the adaptive peak predicted against E. parvula and both beetles
      together. In our experimental population, natural selection imposed by herbivores
      can favor the evolution of mixed defense strategies in plants, accounting for the
      presence of intermediate levels of tolerance and resistance.

PMID- 23171271
TI  - Role of iron homeostasis in the virulence of phytopathogenic bacteria: an 'a la
      carte' menu.
AB  - The interaction between pathogenic microbes and their hosts is determined by
      survival strategies on both sides. As a result of its redox properties, iron is
      vital for the growth and proliferation of nearly all organisms, including
      pathogenic bacteria. In bacteria-vertebrate interactions, competition for this
      essential metal is critical for the outcome of the infection. The role of iron in
      the virulence of plant pathogenic bacteria has only been explored in a few
      pathosystems in the past. However, in the last 5 years, intensive research has
      provided new insights into the mechanisms of iron homeostasis in phytopathogenic
      bacteria that are involved in virulence. This review, which includes important
      plant pathosystems, discusses the recent advances in the understanding of iron
      transport and homeostasis during plant pathogenesis. By summarizing the recent
      progress, we wish to provide an updated view clarifying the various roles played
      by this metal in the virulence of bacterial phytopathogens as a nutritional and
      regulatory element. The complex intertwining of iron metabolism and oxidative
      stress during infection is emphasized.

PMID- 23171272
TI  - Reference values for generic instruments used in routine outcome monitoring: the
      Leiden Routine Outcome Monitoring Study.
AB  - INTRODUCTION: The Brief Symptom Inventory (BSI), Mood & Anxiety Symptom
      Questionnaire -30 (MASQ-D30), Short Form Health Survey 36 (SF-36), and
      Dimensional Assessment of Personality Pathology-Short Form (DAPP-SF) are generic
      instruments that can be used in Routine Outcome Monitoring (ROM) of patients with
      common mental disorders. We aimed to generate reference values usually
      encountered in 'healthy' and 'psychiatrically ill' populations to facilitate
      correct interpretation of ROM results. METHODS: We included the following
      specific reference populations: 1294 subjects from the general population (ROM
      reference group) recruited through general practitioners, and 5269 psychiatric
      outpatients diagnosed with mood, anxiety, or somatoform (MAS) disorders (ROM
      patient group). The outermost 5% of observations were used to define limits for
      one-sided reference intervals (95th percentiles for BSI, MASQ-D30 and DAPP-SF,
      and 5th percentiles for SF-36 subscales). Internal consistency and Receiver
      Operating Characteristics (ROC) analyses were performed. RESULTS: Mean age for
      the ROM reference group was 40.3 years (SD=12.6) and 37.7 years (SD=12.0) for the
      ROM patient group. The proportion of females was 62.8% and 64.6%, respectively.
      The mean for cut-off values of healthy individuals was 0.82 for the BSI
      subscales, 23 for the three MASQ-D30 subscales, 45 for the SF-36 subscales, and
      3.1 for the DAPP-SF subscales. Discriminative power of the BSI, MASQ-D30 and SF
      36 was good, but it was poor for the DAPP-SF. For all instruments, the internal
      consistency of the subscales ranged from adequate to excellent. DISCUSSION AND
      CONCLUSION: Reference values for the clinical interpretation were provided for
      the BSI, MASQ-D30, SF-36, and DAPP-SF. Clinical information aided by ROM data may
      represent the best means to appraise the clinical state of psychiatric
      outpatients.

PMID- 23171273
TI  - Are significant numbers of abnormal cells lost on the discarded ThinPrep(r) broom
      when used for cervical cytology?
AB  - Are significant numbers of abnormal cells lost on the discarded ThinPrep(r) broom
      when used for cervical cytology? BACKGROUND:   In view of a study with
      SurePath(r) showing that cells were lost on the broom if it was discarded, we
      decided to investigate whether cells were lost on the ThinPrep(r) (TP) broom,
      which is discarded according to the manufacturer's protocol. AIM:   To determine
      whether significant amounts of cellular material are lost on the discarded TP
      broom, and whether the loss is operator dependent. METHODS:   Three hundred and
      six women attending the Guy's Hospital Colposcopy Unit gave their consent for TP
      liquid-based cytology samples to be taken and the broom immersed in a second vial
      instead of being discarded. The cellularity of the first and second vials was
      compared by counting cells in 10 *40 high-power fields (HPFs). The significance
      of cell loss was ascertained by correlating the likelihood of abnormal cells and
      transformation zone (TZ) material being present with the degree of cellularity of
      the two vials. RESULTS:   More than 10 cells per HPF were seen in 3.2%, 19.4% and
      35.8% of slides from the second vial taken by three experienced colposcopists,
      which was significantly different between them (P < 0.001); cellularity of the
      first vial was not significantly different between colposcopists but the one with
      highest cellularity in the first vial discarded most in the second. Abnormal
      cells were more likely to be seen in slides with more than 10 cells per HPF (P <
      0.001) and with evidence of TZ sampling (P < 0.001), but there was no
      preferential loss of TZ material in the second vial. Of 126 slides with abnormal
      cells on the slides from the second vial, 113 (89.7%) were also present on the
      significantly more cellular first vial (P < 0.001). CONCLUSION:   Abnormal cells
      were potentially lost on the broom, but were usually represented in the first
      vial. The likelihood of abnormal cells being discarded was operator dependent in
      this small study, but this did not affect the quality of the initial preparation.
      The likelihood of abnormal cells being seen on TP slides was dependent on their
      cellularity, which provided our laboratory with a criterion for the assessment of
      sample adequacy.

PMID- 23171274
TI  - A profile of identity in early-stage dementia and a comparison with healthy older
      people.
AB  - The aim of the study was to determine whether people in the early stages of
      dementia experience their sense of identity differently to healthy older people
      and to examine whether different aspects of identity are related to each other in
      each group. This was a cross-sectional questionnaire-based study; 50 people with
      early-stage dementia and 50 age-matched people without dementia completed
      measures pertaining to different aspects of identity. Measures of mood and self
      esteem were also included so that any differences could be taken into account in
      the analysis. There were very few differences in identity between the groups.
      After differences in levels of anxiety were accounted for, there were no
      differences in scores on most measures of identity. However, people in the early
      stages of dementia scored significantly lower on one subtotal for one measure of
      identity, whereas healthy older adults reported significantly more identity
      related distress than people in the early stages of dementia. For both groups,
      there were no associations between different aspects of identity. People in the
      early stages of dementia do not differ much from healthy older adults in terms of
      their identity. Since healthy older people experience more distress relating to
      identity, they may be more likely to benefit from some sort of intervention than
      people in the early stages of dementia. It might be useful to consider identity
      as consisting of multiple components in future studies, rather than assuming that
      one aspect of identity represents the overall experience of identity.

PMID- 23171275
TI  - Development of factor VIII inhibitors in two patients with moderate haemophilia
      A.

PMID- 23171276
TI  - Nanoplasmonic terahertz photoconductive switch on GaAs.
AB  - Low-temperature (LT) grown GaAs has a subpicosecond carrier response time that
      makes it favorable for terahertz photoconductive (PC) switching. However, this is
      obtained at the price of lower mobility and lower thermal conductivity than GaAs.
      Here we demonstrate subpicosecond carrier sweep-out and over an order of
      magnitude higher sensitivity in detection from a GaAs-based PC switch by using a
      nanoplasmonic structure. As compared to a conventional GaAs PC switch, we observe
      40 times the peak-to-peak response from the nanoplasmonic structure on GaAs. The
      response is double that of a commercial, antireflection coated LT-GaAs PC switch.

PMID- 23171277
TI  - A 10-year content analysis of original research articles published in Health
      Communication and Journal Of Health Communication (2000-2009).
AB  - This study presents data from a content analysis of original research articles
      published in Health Communication and Journal of Health Communication from 2000
      to 2009. The authors coded 776 articles using categories that identified health
      topics, theory, population characteristics, and methods used in each study.
      Distinctions between the published research in Health Communication and Journal
      of Health Communication are highlighted. Across both journals, findings
      demonstrated articles sometimes lack racial demographic information, primarily
      perform research in the United States, rely heavily on survey data, and often
      lack a theoretical framework. The top physical health topic addressed across both
      journals was cancer, and the top non-physical health topic addressed was the role
      of media in health. Journals displayed differences in several areas and those
      differences often mirrored each journal's stated objectives. Results are
      discussed in terms of their implications for expanding health communication
      research to be reflective of issues salient to public health within the United
      States and around the world.

PMID- 23171278
TI  - Long-term trends in PBDEs in sparrowhawk (Accipiter nisus) eggs indicate
      sustained contamination of UK terrestrial ecosystems.
AB  - PBDE contamination in terrestrial biota is poorly characterized, and robust data
      on temporal trends are scarce. We measured temporal (1985-2007) and spatial
      trends in PBDE contamination in the eggs of the sparrowhawk (Accipiter nisus), a
      sentinel for the terrestrial environment. Five BDEs were the most abundant (BDE
      99 > 47 > 153 > 100 > 154). Their concentrations, and that of the sum PBDEs
      (SigmaPBDE), increased from the mid-1980s, peaking in the midlate 1990s at levels
      that were sustained until the end of the study. This and the predominance of
      BDE99 contrast with patterns in piscivorous species and suggest sparrowhawks, and
      perhaps terrestrial species more widely, may be relatively poor metabolizers of
      penta-BDEs. BDE 196, 197, 201, and 203 concentrations increased linearly through
      the study, indicating increasing contamination possibly from the presence of
      these congeners in, and/or debromination of, deca-BDE formulations. Variation in
      egg SigmaPBDE concentration was not explained by % urban land cover, human
      population density or % of arable land in proximity to the nest site, or by land
      use. Overall, egg SigmaPBDE concentrations (34-2281 ng/g wet weight) were some of
      the highest reported in birds from Europe. We found no relationship between
      SigmaPBDE concentrations and eggshell thickness.

PMID- 23171279
TI  - Xiang-Qi-Tang and its active components exhibit anti-inflammatory and
      anticoagulant properties by inhibiting MAPK and NF-kappaB signaling pathways in
      LPS-treated rat cardiac microvascular endothelial cells.
AB  - Xiang-Qi-Tang (XQT) is a Chinese herbal formula containing Cyperus rotundus,
      Astragalus membranaceus and Andrographis paniculata. Alpha-Cyperone (CYP),
      astragaloside IV (AS-IV) and andrographolide (AND) are the three major active
      components in this formula. XQT may modulate the inflammatory or coagulant
      responses. We therefore assessed the effects of XQT on lipopolysaccharide (LPS)
      induced inflammatory model of rat cardiac microvascular endothelial cells
      (RCMECs). XQT, CYP, AS-IV and AND inhibited the production of tumor necrosis
      factor alpha (TNF-alpha), intercellular cell adhesion molecule-1 (ICAM-1) and
      plasminogen activator inhibitor-1 (PAI-1), and up-regulated the mRNA expression
      of Kruppel-like factor 2 (KLF2). XQT and CYP inhibited the secretion of tissue
      factor (TF). To further explore the mechanism, we found that XQT, or its active
      components CYP, AS-IV and AND significantly inhibited extracellular signal
      regulated kinase (ERK), c-jun NH2-terminal kinase (JNK) and p38 phosphorylation
      protein expression as well as decreased the phosphorylation levels of nuclear
      factor kappaB (NF-kappaB) p65 proteins in LPS-stimulated RCMECs. These results
      suggested that XQT and its active components inhibited the expression of
      inflammatory and coagulant mediators via mitogen-activated protein kinase (MAPKs)
      and NF-kappaB signaling pathways. These findings may contribute to future
      research on the action mechanisms of this formula, as well as therapy for
      inflammation- or coagulation-related diseases.

PMID- 23171280
TI  - Functional crosstalk in culture between macrophages and trigeminal sensory
      neurons of a mouse genetic model of migraine.
AB  - BACKGROUND: Enhanced activity of trigeminal ganglion neurons is thought to
      underlie neuronal sensitization facilitating the onset of chronic pain attacks,
      including migraine. Recurrent headache attacks might establish a chronic
      neuroinflammatory ganglion profile contributing to the hypersensitive phenotype.
      Since it is difficult to study this process in vivo, we investigated functional
      crosstalk between macrophages and sensory neurons in primary cultures from
      trigeminal sensory ganglia of wild-type (WT) or knock-in (KI) mice expressing the
      Cacna1a gene mutation (R192Q) found in familial hemiplegic migraine-type 1. After
      studying the number and morphology of resident macrophages in culture, the
      consequences of adding host macrophages on macrophage phagocytosis and membrane
      currents mediated by pain-transducing P2X3 receptors on sensory neurons were
      examined. RESULTS: KI ganglion cultures constitutively contained a larger number
      of active macrophages, although no difference in P2X3 receptor expression was
      found. Co-culturing WT or KI ganglia with host macrophages (active as much as
      resident cells) strongly stimulated single cell phagocytosis. The same protocol
      had no effect on P2X3 receptor expression in WT or KI co-cultures, but it largely
      enhanced WT neuron currents that grew to the high amplitude constitutively seen
      for KI neurons. No further potentiation of KI neuronal currents was observed.
      CONCLUSIONS: Trigeminal ganglion cultures from a genetic mouse model of migraine
      showed basal macrophage activation together with enhanced neuronal currents
      mediated by P2X3 receptors. This phenotype could be replicated in WT cultures by
      adding host macrophages, indicating an important functional crosstalk between
      macrophages and sensory neurons.

PMID- 23171281
TI  - Renal AA-amyloidosis in intravenous drug users--a role for HIV-infection?
AB  - BACKGROUND: Chronic renal disease is a serious complication of long-term
      intravenous drug use (IVDU). Recent reports have postulated a changing pattern of
      underlying nephropathy over the last decades. METHODS: Retrospective
      investigation including all patients with prior or present IVDU that underwent
      renal biopsy because of chronic kidney disease between 01.04.2002 and 31.03.2012
      in the city of Frankfurt/Main, Germany. RESULTS: Twenty four patients with IVDU
      underwent renal biopsy because of progressive chronic kidney disease or
      proteinuria. Renal AA-amyloidosis was the predominant cause of renal failure in
      50% of patients. Membranoproliferative glomerulonephritis (GN) was the second
      most common cause found in 21%. Patients with AA-amyloidosis were more likely to
      be HIV infected (67 vs.17%; p=0.036) and tended to have a higher rate of repeated
      systemic infections (92 vs. 50%; p=0.069). Patients with AA-amyloidosis presented
      with progressive renal disease and nephrotic-range proteinuria but most patients
      had no peripheral edema or systemic hypertension. Development of proteinuria
      preceded the decline of GFR for approximately 1-2 years. CONCLUSIONS: AA
      amyloidosis was the predominant cause of progressive renal disease in the last 10
      years in patients with IVDU. The highest rate of AA-amyloidosis observed was seen
      in HIV infected patients with IVDU. We speculate that chronic HIV-infection as
      well as the associated immunosuppression might promote development of AA
      amyloidosis by increasing frequency and duration of infections acquired by IVDU.

PMID- 23171282
TI  - Is female sexual function related to the male partners' erectile function?
AB  - INTRODUCTION: There are limited data concerning the relationship between the
      sexual functioning of each partner in a heterosexual couple. AIM: This cross
      sectional study was to investigate the association between female sexual function
      and the male partners' erectile function. METHODS: Two self-administered
      questionnaires were used, one distributed to 2,159 female employees of two
      hospitals in Southern Taiwan and the other to their male partners, if available,
      to assess sexual function in each partner of the couple. OUTCOME MEASURE: Female
      sexual function and male erectile function were assessed by the Female Sexual
      Function Index (FSFI) and by the International Index of Erectile Function (IIEF),
      respectively. RESULTS: Among the 1,580 female and 779 male respondents, 632
      sexually active couples were eligible for the analysis with mean ages of 36.9
      years (range 21-67) and 39.5 years (range 18-80) for the women and men,
      respectively. After adjustment for female age group, nearly all the FSFI and IIEF
      domain scores correlated significantly to a slight to moderate degree. On the
      basis of the FSFI and IIEF scores, 42.9% (255/594) of the women reported sexual
      difficulty, and 15.0% (96/632) of the men reported mild to moderate erectile
      dysfunction (ED). After adjustment for female age group, the female partners of
      men with ED had significantly lower total and domain scores of the FSFI than
      those of men without ED, with effect sizes of eta(p)(2) = 0.02-0.08. After
      further adjustment for other risk factors, ED of the male partner was still a
      significant risk factor for female sexual difficulty as well as for sexual
      difficulty in the aspects of arousal, orgasm, sexual satisfaction, and sexual
      pain (odds ratio = 2.5-3.3). CONCLUSIONS: Significant correlations between female
      sexual functioning and male erectile function were identified.

PMID- 23171283
TI  - Thermodynamic properties of hydration water around solutes: effect of solute size
      and water-solute interaction.
AB  - Density, thermal expansion, and heat capacity of hydration water around various
      model solutes have been studied as a function of temperature and pressure. The
      radius of spherical structureless solute was varied from 3 to 10 A, and the water
      solute interaction was varied from strongly hydrophobic to strongly hydrophilic.
      Thermodynamic properties of hydration water around solutes were compared with
      those near the inner surface of large cylindrical pores with a radius of 25 A.
      For all systems studied, the energy of water-water interactions per molecule in
      the hydration shell is found less negative than in the bulk. This is the result
      of the missing neighbor effect, which leads to the liquid density depletion even
      near strongly hydrophilic surfaces. This effect enhances near concave surfaces
      and diminishes near convex surfaces, which causes an essential increase of
      hydration water density around small solutes. Liquid density depletion near
      surfaces is accompanied by an essential increase of the thermal expansion
      coefficient of hydration water: at low temperatures, it exceeds the bulk value
      even near strongly hydrophilic surfaces. The constant volume heat capacity of
      hydration water is close to the bulk value; it is practically not sensitive to
      water-surface interaction and slightly increases upon decreasing solute size. The
      constant pressure heat capacity of hydration water increases upon weakening water
      surface interaction and is practically not sensitive to solute size. Increase of
      the constant pressure heat capacity of water near hydrophobic surfaces is found
      to be the result of the increasing thermal expansion coefficient.

PMID- 23171284
TI  - Psychometric properties of the Taiwanese version of the World Health Organization
      Five Well-Being index.

PMID- 23171285
TI  - Evaluation of anxiolytic activity of compound Valeriana jatamansi Jones in mice.
AB  - BACKGROUND: Compound Valeriana jatamansi Jones is a formula for treating anxiety
      related diseases in the clinic, which is composed of Valeriana jatamansi Rhizoma
      et Radix, Ziziphi Spinosae Semen, Albiziae Cortex and Junci Medulla. The purpose
      of this study was to explore the anxiolytic properties of this compound in mice.
      METHODS: Male ICR mice were treated with compound Valerianae Jatamansi Jones (1.2
      g/kg, 2.4 g/kg, 4.8 g/kg), saline, diazepam (2 mg/kg) orally for 10 days and then
      exposed to elevated maze-plus (EPM) and light-dark box (LDB). The effects of the
      compound on spontaneous activity were evaluated by locomotor activity test. We
      further investigated the mechanism of action underlying the anxiolytic-like
      effect of compound by pre-treating animals with antagonists of benzodiazepine
      (flumazenil, 3mg/kg) prior to evaluation using EPM and LDB. RESULTS: Compound
      Valerianae Jatamansi Jones (2.4, 4.8 g/kg, p.o.) significantly increased entries
      (P<0.05) into and time spent (P<0.05) on the open arms of the EPM, and number of
      transitions (P<0.05) and time spent (P<0.05) in the light compartment of the LDB.
      However, the anxiolytic-like effects of compound were significantly reduced by
      pre-treatment with flumazenil (P>0.05). In addition, compound Valerianae
      Jatamansi Jones treatment didn't affect the spontaneous activity in mice (P>
      0.05). CONCLUSIONS: The present study supports the hypothesis that compound
      Valeriana jatamansi Jones exert anxiolytic action but no sedative effects in mice
      and that this effect might be mediated by benzodiazepine receptors.

PMID- 23171287
TI  - Increased evaporation kinetics of sessile droplets by using nanoparticles.
AB  - The effect of nanoparticles on the evaporation of a sessile droplet into air is
      still controversial. Unlike insoluble surfactants which reduce the droplet
      evaporation rate, here we show that the presence of nanoparticles and the
      increase of their concentration lead to an increase in the overall rate of
      diffusive evaporation and, consequently, a decrease of the droplet lifetime. The
      nanoparticles accumulating at the droplet edge due to the well-known coffee-ring
      effect pin the three-phase contact line for an extended time and maintain a large
      air-water interface area, leading to the increased evaporation rate. We provide a
      full analytical prediction for the lifetime of a sessile droplet evaporating by
      the combined pinned-receding mode. A master equation and a master diagram for the
      droplet lifetime of the combined mode are obtained and experimentally validated,
      and explain the effect of nanoparticles on increasing the global evaporation rate
      and decreasing the droplet lifetime.

PMID- 23171286
TI  - Prospective malaria control using entomopathogenic fungi: comparative evaluation
      of impact on transmission and selection for resistance.
AB  - BACKGROUND: Chemical insecticides against adult mosquitoes are a key element in
      most malaria management programmes, but their efficacy is threatened by the
      evolution of insecticide-resistant mosquitoes. By killing only older mosquitoes,
      entomopathogenic fungi can in principle significantly impact parasite
      transmission while imposing much less selection for resistance. Here an
      assessment is made as to which of the wide range of possible virulence
      characteristics for fungal biopesticides best realise this potential. METHODS:
      With mathematical models that capture relevant timings and survival probabilities
      within successive feeding cycles, transmission and resistance-management metrics
      are used to compare susceptible and resistant mosquitoes exposed to no
      intervention, to conventional instant-kill interventions, and to delayed-action
      biopesticides with a wide range of virulence characteristics. RESULTS: Fungal
      biopesticides that generate high rates of mortality at around the time mosquitoes
      first become able to transmit the malaria parasite offer potential for large
      reductions in transmission while imposing low fitness costs. The best
      combinations of control and resistance management are generally accessed at high
      levels of coverage. Strains which have high virulence in malaria-infected
      mosquitoes but lower virulence in malaria-free mosquitoes offer the ultimate
      benefit in terms of minimizing selection pressure whilst maximizing impact on
      transmission. Exploiting this phenotype should be a target for product
      development. For indoor residual spray programmes, biopesticides may offer
      substantial advantages over the widely used pyrethroid-based insecticides. Not
      only do fungal biopesticides provide substantial resistance management gains in
      the long term, they may also provide greater reductions in transmission before
      resistance has evolved. This is because fungal spores do not have contact
      irritancy, reducing the chances that a blood-fed mosquito can survive an
      encounter and thus live long enough to transmit malaria. CONCLUSIONS: Delayed
      action products, such as fungal biopesticides, have the potential to achieve
      reductions in transmission comparable with those achieved with existing instant
      kill insecticides, and to sustain this control for substantially longer once
      resistant alleles arise. Given the current insecticide resistance crisis, efforts
      should continue to fully explore the operational feasibility of this alternative
      approach.

PMID- 23171288
TI  - Mixed-valence metal oxide nanoparticles as electrochemical half-cells:
      substituting the Ag/AgCl of reference electrodes by CeO(2-x) nanoparticles.
AB  - Cations of mixed valence at surfaces of metal oxide nanoparticles constitute
      electrochemical half-cells, with potentials intermediate between those of the
      dissolved cations and those in the solid. When only cations at surfaces of the
      particles are electrochemically active, the ratio of electrochemically active/all
      cations is ~0.1 for 15 nm diameter CeO(2-x) particles. CeO(2-x) nanoparticle
      loaded hydrogel films on printed carbon and on sputtered gold constitute
      reference electrodes having a redox potential similar to that of Ag/AgCl in
      physiological (0.14 M) saline solutions. In vitro the characteristics of
      potentially subcutaneously implantable glucose monitoring sensors made with CeO(2
      x) nanoparticle reference electrodes are undistinguishable from those of sensors
      made with Ag/AgCl reference electrodes. Cerium is 900 times more abundant than
      silver, and commercially produced CeO(2-x) nanoparticle solutions are available
      at prices well below those of the Ag/AgCl pastes used in the annual manufacture
      of ~10(9) reference electrodes of glucose monitoring strips for diabetes
      management.

PMID- 23171289
TI  - Micro-level economic factors and incentives in Children's energy balance related
      behaviours - findings from the ENERGY European cross-section questionnaire
      survey.
AB  - BACKGROUND: To date, most research on obesogenic environments facing school
      children has focused on physical and socio-cultural environments. The role of
      economic factors has been investigated to a much lesser extent. Our objective was
      to explore the association of micro-level economic factors and incentives with
      sports activities and intake of soft drinks and fruit juice in 10-12 year-old
      school children across Europe, and to explore price sensitivity in children's
      soft drink consumption and correlates of this price sensitivity. METHODS: Data
      for the study originate from a cross-sectional survey undertaken in seven
      European countries (Belgium, Greece, Hungary, Netherlands, Norway, Slovenia and
      Spain) in 2010 among 10-12 year-old school children and their parents. In total,
      7234 child questionnaires and 6002 parent questionnaires were completed. The
      child questionnaire included questions addressing self-reported weekly intake of
      soft drinks and fruit juices and time spent on sports activities, perception of
      parental support for sports activities, use of pocket money for soft drinks and
      perceived price responsiveness. Parent questionnaires included questions
      addressing the role of budget and price considerations in decisions regarding
      children's sports activities, soft drink consumption, home practices and rules
      and socio-demographic background variables. Data were analysed using multiple
      linear regression and discrete-choice (ordered probit) modelling. RESULTS:
      Economic factors were found to be associated with children's sports participation
      and sugary drink consumption, explaining 27% of the variation in time for sports
      activities, and 27% and 12% of the variation in the children's soft drink and
      juice consumption, respectively. Parents' financial support was found to be an
      important correlate (Beta =0.419) of children's sports activities. Children's
      pocket money was a strong correlate (Beta =21.034) of soft drink consumption. The
      majority of the responding children reported to expect that significantly higher
      prices of soft drinks would lead them to buy less soft drinks with their own
      pocket money, but a majority of parents did not expect higher soft drink prices
      to reduce their children's soft drink consumption. CONCLUSIONS: We conclude that
      economic factors, especially parents' financial support and amount of pocket
      money, appear to be of importance for children's sports participation and soft
      drink consumption, respectively.

PMID- 23171290
TI  - Treatment patterns, visual acuity and quality-of-life outcomes of the WAVE study 
      a noninterventional study of ranibizumab treatment for neovascular age-related
      macular degeneration in Germany.
AB  - PURPOSE: To evaluate effectiveness, tolerability and safety of repeated
      intravitreal injections of 0.5 mg ranibizumab for the treatment of neovascular
      age-related macular degeneration in routine medical practice in Germany. METHODS:
      A noninterventional study with 3470 patients treated in 274 medical centres
      according to German guidelines, with monthly intravitreal injections of 0.5 mg
      ranibizumab during upload (3 months) followed by a maintenance phase (9 months)
      with reinjections if medically indicated. RESULTS: Mean injection rate was 4.34
      (SE = 0.05; median = 3.0). Best-corrected visual acuity (BCVA) remained stable
      (mean change 0.02 LogMAR, SE = 0.01, p = 0.0169) and central retinal thickness
      (CRT) decreased (by -78.9 MUm, SE = 2.95 MUm, p < 0.0001). The NEI-VFQ 25 summary
      score showed a positive stabilization with a mean change of 0.73 (SE = 0.37, p =
      0.0501) compared with baseline. Adverse events were documented for 6.5% of the
      patients with 3.9% of these events being classified as serious. CONCLUSIONS: The
      number of administered intravitreal injections of ranibizumab over the first year
      of treatment was very low but still achieved a stabilization of BCVA, a reduction
      in CRT and maintained vision-related quality of life. The management of patients
      with neovascular AMD in Germany needs to be improved to achieve better treatment
      results.

PMID- 23171291
TI  - Physical sexual and intimate relationship concerns among Indonesian cervical
      cancer survivors: A phenomenological study.
AB  - Cervical cancer often leads to sexuality and intimacy concerns for the affected
      woman within a marital relationship.This study aimed to explore physical sexual
      concerns and their impact on the intimate partner relationships experienced by
      cervical cancer survivors. Using a descriptive phenomenological approach, data
      were collected through in-depth interviews with Indonesian women survivors of
      cervical cancer. Two themes and five sub-themes were constructed from the
      thematic analysis. The first theme was the physical sexual concerns following
      cervical cancer treatment, with the subthemes: red spotting and massive vaginal
      discharge after having sexual intercourse; narrower, smaller and less lubricated
      vagina; pain during sexual intercourse; feeling of shortened vagina as if it had
      been cut. The second theme of impact of sexual concerns on intimate partner had
      five subthemes of: looking for reasons to refuse sexual intercourse; prejudice
      towards the spouse; feeling forced to fulfil husband's sexual needs; accepting
      spouse's anger; willingness to let the spouse marry another woman. The findings
      provide nurses with a greater understanding on how women adapt to their altered
      sexuality and intimacy with their partner following cancer treatments. 

PMID- 23171292
TI  - Fungal palaeodiversity revealed using high-throughput metabarcoding of ancient
      DNA from arctic permafrost.
AB  - The taxonomic and ecological diversity of ancient fungal communities was assessed
      by combining next generation sequencing and metabarcoding of DNA preserved in
      permafrost. Twenty-six sediment samples dated 16 000-32 000 radiocarbon years old
      from two localities in Siberia were analysed for fungal ITS. We detected 75
      fungal OTUs from 21 orders representing three phyla, although rarefaction
      analyses suggested that the full diversity was not recovered despite generating
      an average of 6677 +/- 3811 (mean +/- SD) sequences per sample and that
      preservation bias likely has considerable effect on the recovered DNA. Most OTUs
      (75.4%) represented ascomycetes. Due to insufficient sequencing depth, DNA
      degradation and putative preservation biases in our samples, the recovered taxa
      probably do not represent the complete historic fungal community, and it is
      difficult to determine whether the fungal communities varied geographically or
      experienced a composition shift within the period of 16 000-32 000 bp. However,
      annotation of OTUs to functional ecological groups provided a wealth of
      information on the historic communities. About one-third of the OTUs are presumed
      plant-associates (pathogens, saprotrophs and endophytes) typical of graminoid-
      and forb-rich habitats. We also detected putative insect pathogens, coprophiles
      and keratinophiles likely associated with ancient insect and herbivore faunas.
      The detection of putative insect pathogens, mycoparasites, aquatic fungi and
      endophytes broadens our previous knowledge of the diversity of fungi present in
      Beringian palaeoecosystems. A large group of putatively
      psychrophilic/psychrotolerant fungi was also detected, most likely representing a
      modern, metabolically active fungal community.

PMID- 23171293
TI  - Chronic myelogenous leukemia presenting in blast phase with nodal, bilineal
      myeloid sarcoma and T-lymphoblastic lymphoma in a child.
AB  - A 14-year-old boy presented with chronic myelogenous leukemia (CML) in blast
      phase with segregated extramedullary (nodal) myeloid sarcoma and T-lymphoblastic
      lymphoma. Immunohistochemical stains performed on the lymphadenectomy sample
      demonstrated T lymphoblasts in the lymph nodes and myeloblasts in the adjacent
      soft tissue. Fluorescence in situ hybridization performed on paraffin sections
      confirmed that both T-lymphoblast and myeloblast populations were positive for
      the t(9;22) BCR/ABL1 translocation. Subsequent flow cytometry analysis of the
      bone marrow showed expanded populations of abnormal myeloblasts and T
      lymphoblasts diagnostic of blast phase CML. To the best of our knowledge,
      bilineal blast phase of CML with segregated extramedullary T lymphoblasts and
      myeloblasts has not been reported.

PMID- 23171294
TI  - Limitations and possibilities of low cell number ChIP-seq.
AB  - BACKGROUND: Chromatin immunoprecipitation coupled with high-throughput DNA
      sequencing (ChIP-seq) offers high resolution, genome-wide analysis of DNA-protein
      interactions. However, current standard methods require abundant starting
      material in the range of 1-20 million cells per immunoprecipitation, and remain a
      bottleneck to the acquisition of biologically relevant epigenetic data. Using a
      ChIP-seq protocol optimised for low cell numbers (down to 100,000 cells/IP), we
      examined the performance of the ChIP-seq technique on a series of decreasing cell
      numbers. RESULTS: We present an enhanced native ChIP-seq method tailored to low
      cell numbers that represents a 200-fold reduction in input requirements over
      existing protocols. The protocol was tested over a range of starting cell numbers
      covering three orders of magnitude, enabling determination of the lower limit of
      the technique. At low input cell numbers, increased levels of unmapped and
      duplicate reads reduce the number of unique reads generated, and can drive up
      sequencing costs and affect sensitivity if ChIP is attempted from too few cells.
      CONCLUSIONS: The optimised method presented here considerably reduces the input
      requirements for performing native ChIP-seq. It extends the applicability of the
      technique to isolated primary cells and rare cell populations (e.g. biobank
      samples, stem cells), and in many cases will alleviate the need for cell culture
      and any associated alteration of epigenetic marks. However, this study highlights
      a challenge inherent to ChIP-seq from low cell numbers: as cell input numbers
      fall, levels of unmapped sequence reads and PCR-generated duplicate reads rise.
      We discuss a number of solutions to overcome the effects of reducing cell number
      that may aid further improvements to ChIP performance.

PMID- 23171295
TI  - Exclusionary interactions among diverse fungi infecting developing seeds of
      Centaurea stoebe.
AB  - Developing seeds are expected to be strongly defended against microbial attack.
      In keeping with this, only 26% of seeds of Centaurea stoebe from its native and
      invaded ranges in Eurasia and North America were infected with fungi, and 92.2%
      of those were infected with a single fungus per seed. Even when developing seeds
      in flower heads were inoculated under conducive conditions for infection with 14
      of these seed-infecting fungi, re-isolation of inoculants was only 16% overall,
      and again limited to the particular inoculant. Environmental fungi (i.e. those
      not isolated from seed of C. stoebe) were present in control flower heads under
      conditions conducive to infection but they were never re-isolated from fully
      developed seeds in any experiments. When two or three seed isolates were co
      inoculated to compete in flower heads, only one inoculant, and always the same
      one, was re-isolated from all matured seeds, regardless of maternal plant
      genotype. PCR-based detection methods confirmed that these fungal interactions
      were exclusionary rather than suppressive. In these strongly defended, developing
      seeds, we had expected the plant to control not only the overall level of
      infection but also the outcome of co-inoculations. Consequences for the next
      plant generation of this exclusionary competition among seed-infecting fungi
      included effects on seedling emergence, growth and fecundity.

PMID- 23171296
TI  - Joint evolution of seed traits along an aridity gradient: seed size and dormancy
      are not two substitutable evolutionary traits in temporally heterogeneous
      environment.
AB  - Seed size and dormancy are reproductive traits that interact as adaptations to
      environmental conditions. Here, we explore the evolution of these traits in
      environments that differ in overall mean favorability and in the extent of
      temporal predictability. Our model simulates a population of annual plants living
      in a range of environments that differ in aridity, namely mean annual
      precipitation and inter-annual variation of this mean precipitation. The optimal
      fitness curve is investigated assuming density dependence, three alternative
      hypothetical relationships between seed mass and seed survival in the soil
      (negative, positive, and independent of mass), and three alternative
      relationships between survival in soil and precipitation (strong and intermediate
      negative relationships, and no relationship). Our results show that seed size and
      dormancy are not two substitutable evolutionary traits; that specific
      combinations of these two traits are selected in environments that differ in
      favorability and temporal predictability; that a certain degree of seed dormancy
      is advantageous not only in temporally unpredictable environments but also in
      temporally predictable environments with high competition; and that more than one
      combination of seed size and dormancy (defined in terms of germination fraction)
      can be optimal, even in spatially homogeneous environments, potentially allowing
      selection for more variation in these traits within and among species.

PMID- 23171297
TI  - Quantifying individual variation in behaviour: mixed-effect modelling approaches.
AB  - Growing interest in proximate and ultimate causes and consequences of between-
      and within-individual variation in labile components of the phenotype - such as
      behaviour or physiology - characterizes current research in evolutionary ecology.
      The study of individual variation requires tools for quantification and
      decomposition of phenotypic variation into between- and within-individual
      components. This is essential as variance components differ in their ecological
      and evolutionary implications. We provide an overview of how mixed-effect models
      can be used to partition variation in, and correlations among, phenotypic
      attributes into between- and within-individual variance components. Optimal
      sampling schemes to accurately estimate (with sufficient power) a wide range of
      repeatabilities and key (co)variance components, such as between- and within
      individual correlations, are detailed. Mixed-effect models enable the usage of
      unambiguous terminology for patterns of biological variation that currently lack
      a formal statistical definition (e.g. 'animal personality' or 'behavioural
      syndromes'), and facilitate cross-fertilisation between disciplines such as
      behavioural ecology, ecological physiology and quantitative genetics.

PMID- 23171298
TI  - A wish to know but not always tell -- couples living with dementia talk about
      disclosure preferences.
AB  - Most research on disclosure issues in dementia has focused on what it is like to
      receive a dementia diagnosis. Little is known about the disclosure preferences
      that people with dementia and their cohabiting spouses have. In this study, we
      explore disclosure preferences and focus on what couples living with dementia
      want to know and tell about the disease. The study is based on 40 qualitative
      interviews (20 with people with dementia and 20 with their spouses). The analysis
      revealed five preference patterns regarding what the couples wanted to know and
      how they felt about sharing information concerning the disease with others. The
      patterns have been called: (1) want to know and tell (no reservations about it);
      (2) want to know and tell (some reservations about it); (3) want to know but do
      not want to tell; (4) want to know but cannot decide if we want to tell and (5)
      cannot agree on either knowing or telling. They show that couples' preferences
      about what they want to know are related to what they are willing to tell. The
      findings also show that it is usually the preferences of the person that has a
      dementia diagnosis that guide the stand that couples take as far as disclosure
      issues are concerned. Thus, the findings show the type of interdependence that
      exists when one person in a couple has received the diagnosis, and the life of
      the two people as a couple is challenged as a result of this.

PMID- 23171299
TI  - The year's end.

PMID- 23171300
TI  - Blood transfusion safety: a new philosophy.
AB  - Blood transfusion safety has had a chequered history, and there are current and
      future challenges. Internationally, there is no clear consensus for many aspects
      of the provision of safe blood, although pan-national legislation does provide a
      baseline framework in the European Union. Costs are rising, and new safety
      measures can appear expensive, especially when tested against some other medical
      interventions, such as cancer treatment and vaccination programmes. In this
      article, it is proposed that a comprehensive approach is taken to the issue of
      blood transfusion safety that considers all aspects of the process rather than
      considering only new measures. The need for an agreed level of safety for
      specified and unknown risks is also suggested. The importance of providing care
      and support for those inadvertently injured as a result of transfusion problems
      is also made. Given that the current blood safety decision process often uses a
      utilitarian principle for decision making--through the calculation of Quality
      Adjusted Life Years--an alternative philosophy is proposed. A social contract for
      blood safety, based on the principles of 'justice as fairness' developed by John
      Rawls, is recommended as a means of providing an agreed level of safety,
      containing costs and providing support for any adverse outcomes.

PMID- 23171302
TI  - Plasmon-exciton hybridization in ZnO quantum-well Al nanodisc heterostructures.
AB  - We demonstrate the formation of a hybridized plasmon-exciton state exhibiting
      strong exciton-plasmon coupling in ZnO/Zn(0.85)Mg(0.15)O single quantum wells
      capped with arrays of Al nanodiscs. Tuning the quantum-well width and the
      diameter and pitch of the Al nanodisc arrays facilitates a transition from the
      weak-coupling regime into the strong coupling regime. Finite-difference time
      domain simulations substantiate the localization of the plasmonic quadrupole
      moment within the ZnO quantum-well layer, resulting in a hybridized
      plasmonexciton state demonstrating a Rabi splitting of roughly 15 meV in
      heterostructures that exhibit a prominent plasmon quadrupole mode. The
      significant tunability offered by quantum-well heterostructures like those
      discussed here provides a flexible system for controlling exciton plasmon
      coupling in a device-compatible thin-film architecture.

PMID- 23171303
TI  - Suppression of the SUGAR-DEPENDENT1 triacylglycerol lipase family during seed
      development enhances oil yield in oilseed rape (Brassica napus L.).
AB  - Increasing the productivity of oilseed crops is an important challenge for plant
      breeders and biotechnologists. To date, attempts to increase oil production in
      seeds via metabolic pathway engineering have focused on boosting synthetic
      capacity. However, in the tissues of many organisms, it is well established that
      oil levels are determined by both anabolism and catabolism. Indeed, the oil
      content of rapeseed (Brassica napus L.) has been reported to decline by
      approximately 10% in the final stage of development, as the seeds desiccate.
      Here, we show that RNAi suppression of the SUGAR-DEPENDENT1 triacylglycerol
      lipase gene family during seed development results in up to an 8% gain in oil
      yield on either a seed, plant or unit area basis in the greenhouse, with very
      little adverse impact on seed vigour. Suppression of lipolysis could therefore
      constitute a new method for enhancing oil yield in oilseed crops.

PMID- 23171304
TI  - A randomised controlled trial of recovery focused CBT for individuals with early
      bipolar disorder.
AB  - BACKGROUND: There is increasing evidence for the effectiveness of structured
      psychological therapies for bipolar disorder. To date however there have been no
      psychological interventions specifically designed for individuals with early
      bipolar disorder. The primary objective of this trial is to establish the
      acceptability and feasibility of a new CBT based intervention (Recovery focused
      CBT; RfCBT) designed in collaboration with individuals with early bipolar
      disorder intended to improve clinical and personal recovery outcomes. METHODS AND
      DESIGN: This article describes a single blind randomised controlled trial to
      assess the feasibility and acceptability of RfCBT compared with treatment as
      usual. Participants will be recruited from across the North West of England from
      specialist mental health services and through primary care and self referral. The
      primary outcome of the study is the feasibility and acceptability of RfCBT as
      indicated by recruitment to target and retention to follow-up as well as absence
      of untoward incidents associated with RfCBT. We also intend to estimate the
      effect size of the impact of the intervention on recovery and mood outcomes and
      explore potential process measures (self appraisal, stigma, hope and self
      esteem). DISCUSSION: This is the first trial of recovery informed CBT for early
      bipolar disorder and will therefore be of interest to researchers in this area as
      well as indicating the wider potential for evaluating approaches to the recovery
      informed treatment of recent onset severe mental illness in general. TRIAL
      REGISTRATION NUMBER: ISRCTN43062149.

PMID- 23171305
TI  - Heterogeneous reactions of particulate methoxyphenols with NO3 radicals:
      kinetics, products, and mechanisms.
AB  - Methoxyphenols, tracers for wood smoke, are emitted into the atmosphere in large
      quantities, but their chemical degradation in the atmosphere has not been well
      characterized. In this study, heterogeneous kinetics of particulate
      syringaldehyde (SA), vanillic acid (VA), and coniferyl aldehyde (CA) with NO3
      radicals is investigated with a mixed-phase relative rate method. A vacuum
      ultraviolet photoionization aerosol time-of-flight mass spectrometer and an
      atmospheric gas analysis mass spectrometer are used to monitor online the decays
      of particulate methoxyphenols and gas-phase isoprene synchronously. The reactive
      uptake coefficients of NO3 radicals on SA, VA, and CA particles are calculated to
      be 0.33, 0.31, and 0.28, respectively, according to the measured methoxyphenol
      loss ratios and the average NO3 concentrations. The effective rate constants for
      heterogeneous reactions of particulate SA, VA, and CA with NO3 radicals measured
      under experimental conditions are 5.7 * 10-12, 5.2 * 10-12, and 3.5 * 10-12 cm3
      molecule-1 s-1, respectively. In addition, oxalic acid, 2,6
      dimethoxybenzoquinone, 5-nitro-VA, 4,6-dinitrogaiacol, protocatechuic acid,
      vanillin, 5-nitrovanillin, VA, and 5-nitro-CA are identified as the reaction
      products by gas chromatography-mass spectrometry analysis. On the basis of the
      identified products, the reaction mechanisms of methoxyphenols with NO3 radicals
      are proposed. The main transformation pathway of methoxyphenols is the NO3
      electrophilic addition, followed by H-abstraction and nitro-substituted
      processes. The experimental results might shed light on the chemical behaviors of
      methoxyphenols at night.

PMID- 23171306
TI  - Solvent-free tissue processing using supercritical carbon dioxide.
AB  - AIMS: Xylene is most often employed in tissue processing protocols for paraffin
      embedding, but poses a health hazard. The aim of this study was to evaluate a
      solvent-free processing protocol that uses supercritical carbon dioxide (scCO(2)
      ) as an intermediate. METHODS AND RESULTS: A series of tests (with bovine
      tissues) was run, evaluating dehydration and tissue shrinkage in our new scCO(2) 
      based protocol as compared with routine processing using a graded ethanol and
      xylene series. A series of tests was then run to evaluate the significance of
      processing parameters for the outcome. Finally, a validation series was performed
      with optimal conditions, testing various human tissues with several staining
      methods. The tissue water content after paraffination was the same with our new
      scCO(2) -based protocol and the routine xylene-based protocol. Tissue shrinkage
      was similar with the two methods, at ~15%, which is also similar to values in the
      literature. In the validation series, the human tissues showed good morphology
      with strong staining, probably because of stronger antigenicity. CONCLUSIONS:
      This scCO(2) -based protocol has been shown to be a good solvent-free,
      alternative form of tissue processing. Although not the focus of this article,
      the time needed for tissue processing with this new protocol is within 4 h, and
      there is no need to change macroscopy/sectioning protocols.

PMID- 23171307
TI  - Long-term outcomes in haemophilic synovitis after radiosynovectomy using rhenium
      186: a single-centre experience.
AB  - Radiosynovectomy has been performed successfully for more than 10 years in our
      hospital. This study investigated the long-term outcome in the context of time to
      progression (TTP) analysis and the factors influencing TTP following
      radiosynovectomy with Re-186 in patients with haemophilic synovitis.
      Radiosynovectomy performed in 165 joints (81 elbows, 74 ankles, 8 shoulder and 2
      hip joints) of 106 patients (median age was 18.0 +/- 7.5 years; 91 haemophilia A,
      13 haemophilia B and 2 von Willebrand's disease between June 2001 and July 2011.
      The mean follow-up was 48 months (range: 9-120 months). This study revealed that
      patients' mean TTP after primary radiosynovectomy was satisfactory for both the
      ankle and elbow joints. There was no TTP differences between the ankle and elbow
      joint groups (67 vs. 72 months respectively; P = 0.22). We did not find a
      relationship between the TTP and the following variables: age, type and severity
      of haemophilia, the presence or absence of inhibitor, the radiological score,
      range of motion (ROM) status of joints and the pretreatment bleeding frequency.
      In this study, 18-20% of the treated joints had improved ROM and 82-79% of the
      treated joints had unchanged ROM after treatment both the ankle and elbow joints
      respectively. In this report including TTP analysis in the largest series with
      long-term follow-up, we demonstrated long-term effectiveness of Re-186
      radiosynovectomy in haemophilic synovitis. In our experience, the main predictor
      of outcome following radiosynovectomy is the number of joint bleeding within 6
      months after therapy.

PMID- 23171308
TI  - A revolutionary road: an analysis of persons living with hepatitis B in China.
AB  - This study explores the interactions of the environmental barriers, coping
      behaviors, and personal characteristics of persons living with hepatitis B in
      China within the framework of Bandura's social cognitive theory. An analysis of
      1,607 messages from an online support group revealed multiple barriers including
      institutional discrimination, relationship difficulty, alcohol-drinking social
      norm, limitations of the health care system and pharmaceutical market, and
      financial constraints. Major coping behaviors were identified as seeking health
      and reproductive advice, avoiding disclosure and discrimination, protecting legal
      rights, preventing transmission, and outreaching support behaviors. At the
      intrapersonal level, a combatant identity was constructed in the online
      community. The combatant identity was significantly associated with high self
      efficacy, positive emotions, and outreaching support behaviors, but it was not
      significantly associated with environmental barriers. The constructed online
      combatant identity appeared to be support-focused instead of politically
      oriented.

PMID- 23171310
TI  - The experiences of mothers of children with autism: managing multiple roles.
AB  - BACKGROUND: Mothers of children with autism experience poorer health and
      wellbeing compared to mothers of children with other disabilities or typically
      developing children. This qualitative phenomenological study aimed to explore the
      daily life experiences of mothers of children with autism, and the strategies
      they use to manage their roles, their emotions, and their child's behaviours.
      METHOD: In-depth interviews were conducted with 7 mothers and the data were
      analysed using interpretative phenomenological analysis. RESULTS: Findings
      revealed that the mothers were challenged by the demands of their multiple roles
      while dealing with the paradox of accepting their child for who they were, and at
      the same time also desiring their typical growth and development. However, the
      mothers reported various strategies they used to manage their roles, their
      emotions, and their child's behaviours. CONCLUSIONS: The findings indicate that
      health professionals working with these families must support mothers in managing
      various aspects of their lives, including those not directly related to their
      child with autism.

PMID- 23171309
TI  - miRNA164-directed cleavage of ZmNAC1 confers lateral root development in maize
      (Zea mays L.).
AB  - BACKGROUND: MicroRNAs are a class of small, non-coding RNAs that regulate gene
      expression by binding target mRNA, which leads to cleavage or translational
      inhibition. The NAC proteins, which include NAM, ATAF, and CUC, are a plant
      specific transcription factor family with diverse roles in development and stress
      regulation. It has been reported that miR164 negatively regulates NAC1
      expression, which in turn affects lateral root development in Arabidopsis;
      however, little is known about the involvement of the maize NAC family and miR164
      in lateral root development. RESULTS: We collected 175 maize transcripts with NAC
      domains. Of these, 7 ZmNACs were putative targets for regulation by miR164. We
      isolated one gene, called TC258020 (designated ZmNAC1) from 2 maize inbred lines,
      87-1 and Zong3. ZmNAC1 had a high expression level in roots and showed higher
      abundance (1.8 fold) in Zong3 relative to 87-1, which had less lateral roots than
      Zong3. There was a significant correlation between the expression level of ZmNAC1
      and the lateral root density in the recombinant inbred line (RIL) population.
      Transgenic Arabidopsis that overexpressed ZmNAC1 had increased lateral roots in
      comparison to the wild type. These findings suggest that ZmNAC1 played a
      significant role in lateral root development. An allelic expression assay showed
      that trans-regulatory elements were the dominant mediators of ZmNAC1 differential
      expression in 87-1 and Zong3, and further analysis revealed that miR164 was a
      trans-element that guided the cleavage of endogenous ZmNAC1 mRNA. Both mature
      miR164 and miR164 precursors had higher expression in 87-1 than Zong3, which was
      the opposite of the expression pattern of ZmNAC1. Additionally, the allelic assay
      showed that the cis-regulatory element most likely affected Zm-miR164b's
      expression pattern. A beta-glucuronidase (GUS) assay showed that the Zm-miR164b
      promoter had higher GUS activity in 87-1 than in Zong3. In addition, we detected
      miR164b expression in the RIL population, and the results indicated that miR164b
      had a higher expression level in the RILs containing 87-1 promoter than those
      containing Zong3 promoter. CONCLUSION: Our results indicate one possible pathway
      in maize by which differences in miR164b promoter activity resulted in a
      different expression pattern for mature miR164 which negatively regulates ZmNAC1
      expression in 87-1 and Zong3, thereby contributing to a significantly different
      lateral root phenotype.

PMID- 23171311
TI  - The perceptions and experiences of adolescent siblings who have a brother with
      autism spectrum disorder.
AB  - BACKGROUND: There is a dearth of research on the perspectives of adolescent
      siblings growing up with a brother or sister with an autism spectrum disorder
      (ASD). METHOD: Semistructured interviews were used to elicit the perceptions and
      experiences of 12 typically developing adolescents with a brother with an ASD.
      Interpretative phenomenological analysis was used. RESULTS: The data analysis of
      the siblings' perceptions yielded 6 themes: (a) difficulties and negative impact
      of their brother's condition on themselves and their family, (b) how others'
      reactions to their brother negatively affected them as siblings, (c) how their
      histories with their brothers contextualised their present circumstances, (d) the
      varying degrees of acceptance and tolerance towards their brothers, (e) positive
      perceptions and experiences with their brothers, and (f) their thoughts and
      worries about the future. CONCLUSIONS: The main implications are for supports to
      adolescent siblings by helping them to develop skills in managing others'
      reactions and openly discussing concerns about their brother's future.

PMID- 23171312
TI  - A model of processes that underpin positive relationships for adults with severe
      intellectual disability.
AB  - BACKGROUND: Relationships develop through social interaction and assist with
      participation and inclusion. Little is known about how relationships develop
      between people with severe intellectual disability who have limited communication
      and others. METHOD: Interactions were observed between 6 adults with severe
      intellectual disability and paid workers or family members with whom those adults
      had positive relationships. Workers and family members were interviewed. The data
      were analysed through a grounded theory approach. RESULTS: Data analysis led to
      the identification of 5 processes that underpin positive relationships:
      recognising individuality, sharing the moment, connecting, feeling good, and
      sharing the message. CONCLUSIONS: A relationship model with clearly identified
      processes and sub-elements provides a framework for teaching others how to have
      positive relationships with people with severe intellectual disability. The model
      could be applied in training to support relationships between workers and people
      with a disability and more widely with other community members.

PMID- 23171315
TI  - Acute symptomatic hypoglycaemia mimicking ischaemic stroke on imaging: a systemic
      review.
AB  - BACKGROUND: Acute symptomatic hypoglycaemia is a differential diagnosis in
      patients presenting with stroke-like neurological impairment, but few textbooks
      describe the full brain imaging appearances. We systematically reviewed the
      literature to identify how often hypoglycaemia may mimic ischaemic stroke on
      imaging, common patterns and relationships with hypoglycaemia severity, duration,
      clinical outcome and add two new cases. METHODS: We searched EMBASE and Medline
      databases for papers reporting imaging in adults with symptomatic hypoglycaemia.
      We analysed the clinical presentation, outcome, brain imaging findings, duration
      and severity of hypoglycaemia, time course of lesion appearance, including two
      new cases. RESULTS: We found 42 papers describing computed tomography or magnetic
      resonance imaging in 65 patients, plus our two cases with symptomatic
      hypoglycaemia. Imaging abnormalities on computed tomography and magnetic
      resonance were uni or bilateral, cortical or sub-cortical. Thirteen (20%)
      mimicked cortical or lacunar stroke. Acute lesions had restricted diffusion on
      magnetic resonance or low attenuation on computed tomography, plus swelling;
      older lesions showed focal atrophy or disappeared, as with ischaemic stroke. The
      association between the depth or duration of hypoglycaemia, the severity or
      extent of neurological deficit, and the imaging abnormalities, was weak.
      CONCLUSION: Imaging abnormalities in patients with hypoglycaemia are uncommon but
      very variable, weakly associated with neurological deficit, and about a fifth
      mimic acute ischaemic stroke. Blood glucose testing should be routine in all
      patients with acute neurological impairment and hypoglycaemia should be included
      in the differential diagnosis of imaging appearances in patients presenting with
      acute stroke.

PMID- 23171316
TI  - Associations of the IL-1F7 gene polymorphisms with rheumatoid arthritis in
      Chinese Han population.
AB  - Our aim was to investigate whether genetic polymorphism of IL-1F7 (rs3811047) was
      involved in the susceptibility to rheumatoid arthritis (RA) in Chinese Han
      population. Single nucleotide polymorphism (SNP) of IL-1F7 gene (rs3811047) was
      analyzed in 184 unrelated Chinese Han patients with RA and 184 healthy controls
      by ligase detection reaction based on high temperature ligase detection reactions
      polymerase chain reaction (LDR-PCR). There were no statistically significant
      differences in the genetic polymorphism (genotypes and allele frequencies) of IL
      1F7 (rs3811047) in the patients with RA compared with control. Although all of
      the clinical and laboratory measures were similar to each other among patients
      with different genotypes, RA patients carrying AA or AG genotypes had lower
      swollen joint count, swollen joint index, rest pain and health assessment
      questionnaire (HAQ) score than that in patients having GG genotype (P < 0.05).
      These findings show that no evidence for the involvement of a pro-inflammatory
      polymorphism in the IL-1F7 in the susceptibility to RA in China. Patients
      carrying A allele had less severe disease activity than those not carrying this
      allele, suggesting that the A allele of IL-1F7 gene (rs3811047) may have a
      protective effect on RA.

PMID- 23171317
TI  - alpha-Casein inhibition mechanism in concanavalin A aggregation process.
AB  - The inhibition of the aggregation in protein solutions is currently a subject of
      great interest in many research fields, from the study of protein-misfolding
      related diseases to pharmaceutics, biotechnology, and food science. alpha(s1)
      Casein, one of the four types of caseins, which are the largest protein component
      of bovine milk, has been found to hinder the aggregation process of several
      proteins, including the amyloid beta-peptide, involved in Alzheimer's disease. To
      shed light into the mechanisms by which casein exerts this chaperon-like
      protective action, we studied its effect on the different steps of the
      aggregation process of concanavalin A, by means of both static and dynamic light
      scattering, thioflavin T and ANS fluorescence, circular dichroism, and atomic
      force microscopy. Our results show that casein has a poor effect on the first
      step of the process leading to the formation of amyloid-like structures. On the
      contrary, it has a marked effect on the second step of the process, ascribable to
      clusters condensation and compaction, up to the formation of very large
      aggregates. Such an effect requires a molar ratio of casein larger than that
      necessary to inhibit the fibrillogenesis of the amyloid beta-peptide, thus,
      suggesting a different mechanism of interaction of casein, depending on both
      conformational properties and relative size of the aggregating molecules.

PMID- 23171318
TI  - Outcomes of child psychiatric treatment.
AB  - OBJECTIVE: The aim of this study was to investigate outcomes of child psychiatric
      outpatient treatment as usual and to identify outcome predictors, with special
      regard to attention-deficit/hyperactivity disorder (ADHD), mood disorder,
      obsessive-compulsive disorder and conduct disorder. METHOD: Routinely collected
      data from 12 613 outpatients between July 2006 and January 2010 in Stockholm,
      Sweden were analysed. The outcome measure was change in Children's Global
      Assessment Scale (CGAS) ratings between first visit and case closure (?CGAS).
      RESULTS: CGAS improved during the course of treatment across all diagnostic
      groups, ranging from a mean change of 4 (mental retardation) to 16 (suicide
      attempts). ?CGAS was two times higher in the mood disorder group compared with
      the ADHD group. In the mood disorder group, several psychotherapies were
      associated with better outcome but not medication. In the ADHD group,
      psychotherapeutic interventions were also associated with better outcome, but
      those who received treatment with central stimulants received less non-medical
      interventions. CONCLUSION: Whereas the functional impairment and the level of
      improvement in mood disorder corresponded to previous efficacy studies, the ADHD
      patients were more impaired and improved less after treatment. This should prompt
      a critical discussion as to whether ADHD patients receive the best available
      treatment in CAMHS in Stockholm and elsewhere.

PMID- 23171320
TI  - Intermittent fasting combined with calorie restriction is effective for weight
      loss and cardio-protection in obese women.
AB  - BACKGROUND: Intermittent fasting (IF; severe restriction 1 d/week) facilitates
      weight loss and improves coronary heart disease (CHD) risk indicators. The degree
      to which weight loss can be enhanced if IF is combined with calorie restriction
      (CR) and liquid meals, remains unknown. OBJECTIVE: This study examined the
      effects of IF plus CR (with or without a liquid diet) on body weight, body
      composition, and CHD risk. METHODS: Obese women (n = 54) were randomized to
      either the IFCR-liquid (IFCR-L) or IFCR-food based (IFCR-F) diet. The trial had
      two phases: 1) 2-week weight maintenance period, and 2) 8-week weight loss
      period. RESULTS: Body weight decreased more (P = 0.04) in the IFCR-L group (3.9
      +/- 1.4 kg) versus the IFCR-F group (2.5 +/- 0.6 kg). Fat mass decreased
      similarly (P < 0.0001) in the IFCR-L and IFCR-F groups (2.8 +/- 1.2 kg and 1.9 +/
      0.7 kg, respectively). Visceral fat was reduced (P < 0.001) by IFCR-L (0.7 +/-
      0.5 kg) and IFCR-F (0.3 +/- 0.5 kg) diets. Reductions in total and LDL
      cholesterol levels were greater (P = 0.04) in the IFCR-L (19 +/- 10%; 20 +/- 9%,
      respectively) versus the IFCR-F group (8 +/- 3%; 7 +/- 4%, respectively). LDL
      peak particle size increased (P < 0.01), while heart rate, glucose, insulin, and
      homocysteine decreased (P < 0.05), in the IFCR-L group only. CONCLUSION: These
      findings suggest that IF combined with CR and liquid meals is an effective
      strategy to help obese women lose weight and lower CHD risk.

PMID- 23171321
TI  - Capillary rise in a microchannel of arbitrary shape and wettability: hysteresis
      loop.
AB  - Capillary rise in an asymmetric microchannel, in which both contact angle
      (wettability) and open angle (geometry) can vary with position, is investigated
      based on free-energy minimization. The integration of the Young-Laplace equation
      yields the general force balance between surface tension and gravity. The former
      is surface tension times the integration of cos theta(u) along the contact line,
      where theta(u) depicts the local difference between contact angle and open angle.
      The latter comes from the total volume right underneath the meniscus. For the
      same channel height, multiple solutions can be obtained from the force balance.
      However, the stable height of capillary rise must satisfy stability analysis.
      Several interesting cases have been studied, including short capillary, truncated
      cone, hyperboloid, and two different plates. As the tube length is smaller than
      Jurin's height, the angle of contact will be tuned to fulfill the force balance.
      While only one stable state is seen for divergent channels, two stable states can
      be observed for convergent channels. Three regimes can be identified for the plot
      of the stable height of capillary rise against the channel height. The higher
      height dominates in the short channel regime, while the lower height prevails in
      the tall channel regime. However, both solutions are stable in the intermediate
      regime. Surface Evolver simulations and experiments are performed to validate our
      theoretical predictions. Our results offer some implications for water transport
      to the tops of tall trees. A small bore at the uppermost leaf connected to a
      larger xylem conduit corresponds to a convergent channel, and two stable heights
      are possible. The slow growth of the tree can be regarded as a gradual rise of
      the convergent channel. Consequently, the stable height of capillary rise to the
      top of a tall tree can always be achieved.

PMID- 23171319
TI  - Protective effect of topical Cordia verbenacea in a rat periodontitis model:
      immune-inflammatory, antibacterial and morphometric assays.
AB  - BACKGROUND: This study evaluated the effects of C. verbenacea essential oil
      topically administered in a rat periodontitis model. METHODS: Periodontitis was
      induced on rats in one of the mandibular first molars assigned to receive a
      ligature. Animals were randomly divided into two groups: a) non-treatment group
      (NT) (n = 18): animals received 1mL of vehicle; b) C. verbenacea group (C.v.) (n
      = 18): animals received 5mg/Kg of essential oils isolated from C. verbenacea. The
      therapies were administered topically 3 times daily for 11 days. Then, the
      specimens were processed for morphometric analysis of bone loss. The ligatures
      were used for microbiological assessment of the presence of Aggregatibacter
      actinomycetemcomitans, Tannerella forsythia and Porphyromonas gingivalis using
      PCR. The gingival tissue was collected to Elisa assay of interleukin (IL)-1alpha
      and IL-10 levels. RESULTS: Bone loss was inhibited by C. verbenacea when compared
      to the NT group (p < 0.05). A decrease in the levels of IL-1alpha and increase in
      the IL-10 amounts was observed in the C.v. group as compared to NT group (p <
      0.05). A lower frequency of P. gingivalis was found in C.v. group (p < 0.05).
      CONCLUSION: C. verbenacea essential oil topically administered diminished
      alveolar bone resorption, promoting a positive local imbalance in the pro/anti
      inflammatory system and reducing the frequency of detection of P. gingivalis.

PMID- 23171322
TI  - New isolable dialkylsilylene and its isolable dimer that equilibrate in solution.
AB  - The new isolable dialkylsilylene 3 bearing a bidentate alkyl substituent was
      synthesized. Recrystallization of silylene 3 gave yellow crystals of 3 and orange
      red crystals of tetraalkyldisilene 4, a dimer of 3. In the solid state, 3 exists
      as a monomer with a closest distance of 6.745 A between dicoordinate silicon
      atoms, while disilene 4 has a remarkably long Si?Si double bond distance of 2.252
      A. An equilibrium between 3 and 4 in solution was observed by NMR and UV-vis
      spectroscopies, and the thermodynamic parameters of the equilibrium were
      estimated to be DeltaH = -36 +/- 3 kJ mol(-1) and DeltaS = -170 +/- 15 J mol(-1)
      K(-1). Analysis of the percent buried volume, a measure of the steric demand
      around the divalent silicon, showed that the flexible steric bulkiness of the
      alkyl substituent of 3 and 4 allows the reversible dimerization of silylene 3 to
      disilene 4 and the isolation of both species.

PMID- 23171324
TI  - Chronic hepatitis B and C: Exploring perceived stigma, disease information, and
      health-related quality of life.
AB  - Research indicates that chronic hepatitis C affects people's quality of life, but
      such reports are scarce about hepatitis B. This Australian study explored whether
      perceived stigma and satisfaction with received information and care were related
      to health-related quality of life in people with chronic hepatitis B or C. A
      questionnaire was constructed comprising demographic questions and existing
      scales to measure the variables. The 77 participants were recruited through
      various online channels. The median age was 48 years, 74% had hepatitis C, 60%
      were female, and 73% were Caucasian. Participants with Hepatitis B reported
      substantially less perceived stigma than those with Hepatitis C, but there was no
      significant difference between the two groups in health-related quality of life.
      Participants with Hepatitis C reported higher satisfaction with received
      information. The results highlight specific aspects to consider in the care of
      people with chronic hepatitis. For example, people with hepatitis B do not seem
      to enjoy better health-related quality of life despite lower perceived
      stigmatization. Therefore, these patients may require other improvements in
      service delivery such as the provision of more culturally appropriate information
      and education about chronic hepatitis B.

PMID- 23171325
TI  - Age-related pupillary miosis should be considered in pseudophakic circadian
      photoreception analysis.

PMID- 23171323
TI  - Impact of passing mesenchymal stem cells through smaller bore size needles for
      subsequent use in patients for clinical or cosmetic indications.
AB  - BACKGROUND: Numerous preclinical and clinical studies have investigated the
      regenerative potential and the trophic support of mesenchymal stem cells (MSCs)
      following their injection into a target organ. Clinicians favor the use of
      smallest bore needles possible for delivering MSCs into vascular organs like
      heart, liver and spleen. There has been a concern that small needle bore sizes
      may be detrimental to the health of these cells and reduce the survival and
      plasticity of MSCs. METHODS: In this report, we aimed to investigate the smallest
      possible bore size needle which would support the safe delivery of MSCs into
      various tissues for different clinical or cosmetic applications. To accomplish
      this we injected cells via needle sizes 24, 25 and 26 G attached to 1 ml syringe
      in the laboratory and collected the cells aseptically. Control cells were ejected
      via 1 ml syringe without any needle. Thereafter, the needle ejected cells were
      cultured and characterized for their morphology, attachment, viability,
      phenotypic expression, differentiation potential, cryopreservation and in vivo
      migration abilities. In the second phase of the study, cells were injected via 26
      G needle attached to 1 ml syringe for 10 times. RESULTS: Similar phenotypic and
      functional characteristics were observed between ejected and control group of
      cells. MSCs maintained their cellular and functional properties after single and
      multiple injections. CONCLUSIONS: This study proves that 26 G bore size needles
      can be safely used to inject MSCs for clinical/therapeutics purposes.

PMID- 23171326
TI  - Friend or foe: genetic and functional characterization of plant endophytic
      Pseudomonas aeruginosa.
AB  - Endophytic Pseudomonas aeruginosa strain BP35 was originally isolated from black
      pepper grown in the rain forest in Kerala, India. Strain PaBP35 was shown to
      provide significant protection to black pepper against infections by Phytophthora
      capsici and Radopholus similis. For registration and implementation in disease
      management programmes, several traits of PaBP35 were investigated including its
      endophytic behaviour, biocontrol activity, phylogeny and toxicity to mammals. The
      results showed that PaBP35 efficiently colonized black pepper shoots and
      displayed a typical spatiotemporal pattern in its endophytic movement with
      concomitant suppression of Phytophthora rot. Confocal laser scanning microscopy
      revealed high populations of PaBP35::gfp2 inside tomato plantlets, supporting its
      endophytic behaviour in other plant species. Polyphasic approaches to genotype
      PaBP35, including BOX-PCR, recN sequence analysis, multilocus sequence typing and
      comparative genome hybridization analysis, revealed its uniqueness among P.
      aeruginosa strains representing clinical habitats. However, like other P.
      aeruginosa strains, PaBP35 exhibited resistance to antibiotics, grew at 25-41
      degrees C and produced rhamnolipids and phenazines. PaBP35 displayed strong type
      II secretion effectors-mediated cytotoxicity on mammalian A549 cells. Coupled
      with pathogenicity in a murine airway infection model, we conclude that this
      plant endophytic strain is as virulent as clinical P. aeruginosa strains. Safety
      issues related to the selection of plant endophytic bacteria for crop protection
      are discussed.

PMID- 23171327
TI  - Working memory performance of older adults with insomnia.
AB  - Older individuals suffering insomnia typically report declines in their cognitive
      performance beyond what they consider to be normal changes due to the aging
      process. Recent neuro-imaging studies have demonstrated frontal lobe hypo
      activation among insomniac populations when compared with healthy, good sleepers.
      However, research is yet to confirm whether frontal lobe hypo-activation
      translates into objective declines when performing tasks hypothesized to draw
      upon this brain region. This study aimed to investigate whether older insomnia
      sufferers demonstrate significantly impaired performance on a challenging working
      memory task when compared with age-matched good sleepers. Forty-nine older
      individuals (mean age = 69.43 years, SD = 4.83) suffering from sleep maintenance
      insomnia were compared with 49 age-matched good sleepers. Cognitive performance
      was assessed using the Double Span Memory Task, a computer-based working memory
      task that requires participants to indicate the names and/or spatial locations of
      increasingly longer sequences of visually presented objects. After controlling
      for general intelligence, the individuals suffering from insomnia did not perform
      differently when compared with the good sleepers on either the simpler or more
      cognitively demanding components of the task. Older individuals with insomnia did
      not display an observable impairment of working memory in this study relative to
      good sleepers. Despite the mixed results from previous research, this study adds
      weight to the absence of objective impairment in insomniacs, at least while
      performing short-term demanding cognitive tasks.

PMID- 23171328
TI  - Role of miRNAs in the response to anticancer therapy.

PMID- 23171329
TI  - Improved, personalized treatment of glioma necessitates long-term follow-up of
      cognitive functioning.

PMID- 23171330
TI  - Current status of clopidogrel pharmacogenomics.

PMID- 23171332
TI  - Pharmacogenetics in solid organ transplantation: a transition from kinetics to
      dynamics.

PMID- 23171333
TI  - Company profile: labceutics.
AB  - Laboratories are often the forgotten partners in the delivery of personalized
      therapies to physicians worldwide, yet the research and quality of their service
      in delivering seamless test results to physicians can either enhance the value
      proposition of a targeted therapy or destroy it. The need for integrated highest
      quality laboratory networks in fragmented markets such as Europe and Asia are
      needed to truly leverage the power of companion diagnostics.

PMID- 23171334
TI  - Allelic combinations of immune-response genes as possible composite markers of
      IFN-beta efficacy in multiple sclerosis patients.
AB  - BACKGROUND: IFN-beta is widely used as the first-line disease-modifying treatment
      for multiple sclerosis. However, 30-50% of multiple sclerosis patients do not
      respond to this therapy. Identification of genetic variants and their
      combinations that predict responsiveness to IFN-beta could be useful for
      treatment prognosis. MATERIALS & METHODS: The combinations of alleles of nine
      polymorphic loci in immune-response genes were analyzed in 253 Russian multiple
      sclerosis patients as possible determinants of clinically optimal IFN-beta
      treatment response using APSampler software. RESULTS: Carriage of TGFB1*-509C and
      CCR5*d was associated with favorable IFN-beta response by itself. CCR5*d,
      IFNAR1*16725G, IFNG*874T and IFNB1*153T/T were the components of the
      combinations, associated with clinically optimal response to IFN-beta. Carriage
      of composite markers (CCR5*d + IFNAR1*G + IFNB1*T/T) or (CCR5*d + IFNAR1*G +
      IFNG*T) is beneficial for IFN-beta treatment efficacy. DISCUSSION: The data
      obtained provides evidence of the cumulative effect of immune-response genes on
      IFN-beta treatment efficacy. This joint contribution may reflect the additive
      effect of independent allelic variants and epistatic interactions between some of
      them.

PMID- 23171335
TI  - DRD2 haplotype is associated with dyskinesia induced by levodopa therapy in
      Parkinson's disease patients.
AB  - AIM: Dyskinesia and motor fluctuation are frequent and serious complications of
      chronic levodopa therapy in patients with Parkinson's disease. Since genetic
      factors could play a role in determining the occurrence of these problems, the
      aim of the present study was to investigate whether possible functional
      polymorphisms among DRD2 and ANKK1 genes are associated with the risk of
      developing dyskinesia and motor fluctuations in Parkinson's disease patients.
      PATIENTS & METHODS: One hundred and ninety nine patients in treatment with
      levodopa were genotyped for the -141CIns/Del, rs2283265, rs1076560, C957T, TaqIA
      and rs2734849 polymorphisms at the DRD2/ANKK1 gene region. RESULTS: Carriers of
      the TTCTA haplotype showed an increased risk for the presence of dyskinesia (p =
      0.007; 1.538 [95% CI: 1.126-2.101]). CONCLUSION: Our data suggest an influence of
      the DRD2/ANKK1 gene region on levodopa-induced dyskinesia.

PMID- 23171337
TI  - Pharmacogenomics of opioids and perioperative pain management.
AB  - Inadequate pain relief and adverse effects from analgesics remain common in
      children and adults during the perioperative period. Opioids are the most
      commonly used analgesics in children and adults to treat perioperative pain.
      Narrow therapeutic index and a large interpatient variability in response to
      opioids are clinically significant, with inadequate pain relief at one end of the
      spectrum and serious side effects, such as respiratory depression and excessive
      sedation due to relative overdosing, at the other end. Personalizing analgesia
      during the perioperative period attempts to maximize pain relief while minimizing
      adverse events from therapy. While various factors influence response to
      treatment among surgical patients, age, sex, race and pharmacogenetic differences
      appear to play major roles in predicting outcome. Genetic factors include a
      subset of genes that modulate the proteins involved in pain perception, pain
      pathway, analgesic metabolism (pharmacokinetics), transport and receptor
      signaling (pharmacodynamics). While results from adult genetic studies can
      provide direction for pediatric studies, they have limited direct applicability,
      as children's genetic predispositions to analgesic response may be influenced by
      developmental and behavioral components, altered sensitivity to analgesics and
      variation in gene-expression patterns. We have reviewed the available evidence on
      improving and personalizing pain management with opioids and the significance of
      individualizing analgesia, in order to maximize analgesic effect with minimal
      adverse effects with opioids. While the early evidence on individual genotype
      associations with pain, analgesia and opioid adverse outcome are promising, the
      large amount of conflicting data in the literature suggests that there is a need
      for larger and more robust studies with appropriate population stratification and
      consideration of nongenetic and other genetic risk factors. Although the clinical
      evidence and the prospect of being able to provide point-of-care genotyping to
      enable clinicians to deliver personalized analgesia for individual patients is
      still not available, positioning our research to identify all possible major
      genetic and nongenetic risk factors of an individual patient, advancing less
      expensive point-of-care genotyping technology and developing easy-to-use
      personalized clinical decision algorithms will help us to improve current
      clinical and economic outcomes associated with pain and opioid pain management.

PMID- 23171338
TI  - Genetics and genomics of ischemic tolerance: focus on cardiac and cerebral
      ischemic preconditioning.
AB  - A subthreshold ischemic insult applied to an organ such as the heart and/or brain
      may help to reduce damage caused by subsequent ischemic episodes. This phenomenon
      is known as ischemic tolerance mediated by ischemic preconditioning (IPC) and
      represents the most powerful endogenous mechanism against ischemic injury.
      Various molecular pathways have been implicated in IPC, and several compounds
      have been proposed as activators or mediators of IPC. Recently, it has been
      established that the protective phenotype in response to ischemia depends on a
      coordinated response at the genomic, molecular, cellular and tissue levels by
      introducing the concept of 'genomic reprogramming' following IPC. In this
      article, we sought to review the genetic expression profiles found in cardiac and
      cerebral IPC studies, describe the differences between young and aged organs in
      IPC-mediated protection, and discuss the potential therapeutic application of IPC
      and pharmacological preconditioning based on the genomic response.

PMID- 23171336
TI  - Losartan hydroxylation phenotype in an Ecuadorian population: influence of CYP2C9
      genetic polymorphism, habits and gender.
AB  - AIM: To describe for the first time CYP2C9 hydroxylation phenotype with CYP2C9
      genotypes in a Hispanic (Ecuadorian) population using losartan; and the relevance
      of gender, tobacco, ethanol and caffeine consumption on the enzyme hydroxylation
      capacity. METHODS: Ecuadorian healthy volunteers (n = 194) received a single oral
      dose of 25 mg losartan. Losartan metabolic ratio was defined as losartan:E3174
      concentration. CYP2C9 alleles *2, *3, *4, *5 and *6 were analyzed. RESULTS: No
      phenotypically poor metabolizers were found. The metabolic ratio (mean +/-
      standard deviation) was higher (p < 0.05) in CYP2C9*1/*3 carriers (12.4 +/- 13.8;
      n = 6) versus CYP2C9*1/*1 (4.9 +/- 7.0; n = 167), as well as in females versus
      males (6.72 +/- 9.72 and 3.76 +/- 4.48, respectively; p < 0.05). Only the
      following genotypes, CYP2C9*1/*1, CYP2C9*1/*2 and CYP2C9*1/*3, were found with a
      frequency of 86.1%, 10.8% and 3.1%, respectively. CONCLUSION: Despite the mean
      metabolic ratio being higher in this population than in others previously studied
      across genotypes, no poor metabolizers, either phenotypically or genotypically,
      were found.

PMID- 23171339
TI  - Pharmacogenomic considerations of xenograft mouse models of acute leukemia.
AB  - The use of combination chemotherapy to cure acute lymphoblastic leukemia in
      children and acute myeloid leukemia in adults emerged for acute myeloid leukemia
      in the 1960s and for acute lymphoblastic leukemia in the 1980s as a paradigm for
      curing any disseminated cancer. This article summarizes recent developments and
      considerations in the use of acute leukemia xenografts established in
      immunodeficient mice to elucidate the genetic and genomic basis of acute leukemia
      pathogenesis and treatment response.

PMID- 23171340
TI  - Strengths and weaknesses of pharmacogenetic studies of antipsychotic drugs: the
      potential value of the PEPs study.
AB  - The successful application of pharmacogenetics in routine clinical practice is
      still a long way from becoming a reality. In order to favor the transfer of
      pharmacogenetic results to clinical practice, especially in psychiatry, these
      studies must be optimized. This article reviews the strengths and weaknesses that
      characterize pharmacogenetic studies in psychiatry and condition their
      implementation in clinical practice. We also include recommendations for
      improving the design of pharmacogenetic studies, which may convert their
      limitations into strengths and facilitate the implementation of their results
      into clinical practice. Finally, we discuss the potential value of naturalistic,
      prospective, multicenter and coordinated projects such as the 'Phenotype-genotype
      and environmental interaction. Application of a predictive model in first
      psychotic episodes' (known as the PEPs study, from the Spanish abbreviation) in
      pharmacogenetic studies.

PMID- 23171342
TI  - Genome sequence of the necrotrophic fungus Penicillium digitatum, the main
      postharvest pathogen of citrus.
AB  - BACKGROUND: Penicillium digitatum is a fungal necrotroph causing a common citrus
      postharvest disease known as green mold. In order to gain insight into the
      genetic bases of its virulence mechanisms and its high degree of host
      specificity, the genomes of two P. digitatum strains that differ in their
      antifungal resistance traits have been sequenced and compared with those of 28
      other Pezizomycotina. RESULTS: The two sequenced genomes are highly similar, but
      important differences between them include the presence of a unique gene cluster
      in the resistant strain, and mutations previously shown to confer fungicide
      resistance. The two strains, which were isolated in Spain, and another isolated
      in China have identical mitochondrial genome sequences suggesting a recent
      worldwide expansion of the species. Comparison with the closely-related but non
      phytopathogenic P. chrysogenum reveals a much smaller gene content in P.
      digitatum, consistent with a more specialized lifestyle. We show that large
      regions of the P. chrysogenum genome, including entire supercontigs, are absent
      from P. digitatum, and that this is the result of large gene family expansions
      rather than acquisition through horizontal gene transfer. Our analysis of the P.
      digitatum genome is indicative of heterothallic sexual reproduction and reveals
      the molecular basis for the inability of this species to assimilate nitrate or
      produce the metabolites patulin and penicillin. Finally, we identify the
      predicted secretome, which provides a first approximation to the protein
      repertoire used during invasive growth. CONCLUSIONS: The complete genome of P.
      digitatum, the first of a phytopathogenic Penicillium species, is a valuable tool
      for understanding the virulence mechanisms and host-specificity of this
      economically important pest.

PMID- 23171343
TI  - Genotype modulates age-related alterations in sensitivity to the aversive effects
      of ethanol: an eight inbred strain analysis of conditioned taste aversion.
AB  - Adolescent individuals display altered behavioral sensitivity to ethanol, which
      may contribute to the increased ethanol consumption seen in this age-group.
      However, genetics also exert considerable influence on both ethanol intake and
      sensitivity. Currently there is little research assessing the combined influence
      of developmental and genetic alcohol sensitivities. Sensitivity to the aversive
      effects of ethanol using a conditioned taste aversion (CTA) procedure was
      measured during both adolescence (P30) and adulthood (P75) in eight inbred mouse
      strains (C57BL/6J, DBA/2J, 129S1/SvImJ, A/J, BALB/cByJ, BTBR T(+) tf/J, C3H/HeJ
      and FVB/NJ). Adolescent and adult mice were water deprived, and subsequently
      provided with access to 0.9% (v/v) NaCl solution for 1 h. Immediately following
      access mice were administered ethanol (0, 1.5, 2.25 and 3 g/kg, ip). This
      procedure was repeated in 72 h intervals for a total of five CTA trials.
      Sensitivity to the aversive effects of ethanol was highly dependent upon both
      strain and age. Within an inbred strain, adolescent animals were consistently
      less sensitive to the aversive effects of ethanol than their adult counterparts.
      However, the dose of ethanol required to produce an aversion response differed as
      a function of both age and strain.

PMID- 23171344
TI  - Vegetation dynamics drive segregation by body size in Galapagos tortoises
      migrating across altitudinal gradients.
AB  - Seasonal migration has evolved in many taxa as a response to predictable spatial
      and temporal variation in the environment. Individual traits, physiology and
      social state interact with environmental factors to increase the complexity of
      migratory systems. Despite a huge body of research, the ultimate causes of
      migration remain unclear. A relatively simple, tractable system - giant tortoises
      on Santa Cruz Island, Galapagos, was studied to elucidate the roles of
      environmental variation and individual traits in a partial migratory system.
      Specifically, we asked: (i) do Galapagos tortoises undergo long-distance seasonal
      migrations? (ii) is tortoise migration ultimately driven by gradients in forage
      quality or temperature; and (iii) how do sex and body size influence migration
      patterns? We recorded the daily locations of 17 GPS-tagged tortoises and walked a
      monthly survey along the altitudinal gradient to characterize the movements and
      distribution of tortoises of different sizes and sexes. Monthly temperature and
      rainfall data were obtained from weather stations deployed at various altitudes,
      and the Normalized Difference Vegetation Index was used as a proxy for forage
      quality. Analyses using net displacement or daily movement characteristics did
      not agree on assigning individuals as either migratory or non-migratory; however,
      both methods suggested that some individuals were migratory. Adult tortoises of
      both sexes move up and down an altitudinal gradient in response to changes in
      vegetation dynamics, not temperature. The largest tagged individuals all moved,
      whereas only some mid-sized individuals moved, and the smallest individuals never
      left lowland areas. The timing of movements varied with body size: large
      individuals moved upward (as lowland forage quality declined) earlier in the year
      than did mid-sized individuals, while the timing of downward movements was
      unrelated to body size and occurred as lowland vegetation productivity peaked.
      Giant tortoises are unlikely candidates for forage-driven migration as they are
      well buffered against environmental fluctuations by large body size and a slow
      metabolism. Notably the largest, and presumably most dominant, individuals were
      most likely to migrate. This characteristic and the lack of sex-based differences
      in movement behaviour distinguish Galapagos tortoise movement from previously
      described partial migratory systems. 

PMID- 23171345
TI  - Four 13-lipoxygenases contribute to rapid jasmonate synthesis in wounded
      Arabidopsis thaliana leaves: a role for lipoxygenase 6 in responses to long
      distance wound signals.
AB  - Damage-inducible defenses in plants are controlled in part by jasmonates, fatty
      acid-derived regulators that start to accumulate within 30 s of wounding a leaf.
      Using liquid chromatography-tandem mass spectrometry, we sought to identify the
      13-lipoxygenases (13-LOXs) that initiate wound-induced jasmonate synthesis within
      a 190-s timeframe in Arabidopsis thaliana in 19 single, double, triple and
      quadruple mutant combinations derived from the four 13-LOX genes in this plant.
      All four 13-LOXs were found to contribute to jasmonate synthesis in wounded
      leaves: among them LOX6 showed a unique behavior. The relative contribution of
      LOX6 to jasmonate synthesis increased with distance from a leaf tip wound, and
      LOX6 was the only 13-LOX necessary for the initiation of early jasmonate
      synthesis in leaves distal to the wounded leaf. Herbivory assays that compared
      Spodoptera littoralis feeding on the lox2-1 lox3B lox4A lox6A quadruple mutant
      and the lox2-1 lox3B lox4A triple mutant revealed a role for LOX6 in defense of
      the shoot apical meristem. Consistent with this, we found that LOX6 promoter
      activity was strong in the apical region of rosettes. The LOX6 promoter was
      active in and near developing xylem cells and in expression domains we term
      subtrichomal mounds.

PMID- 23171346
TI  - THE CANON - 4. Medusa's hair: an essay on personal symbols and religious
      experience, by Gananath Obeyesekere.

PMID- 23171351
TI  - Clinical and radiographic outcomes of the use of four dressing materials in
      pulpotomized primary molars: a randomized clinical trial with 2-year follow-up.
AB  - BACKGROUND: Although multiple materials have been suggested for pulpotomized
      primary molars, there is no reliable evidence of the superiority of one
      particular type. AIM: To compare the effectiveness of formocresol (FC), mineral
      trioxide aggregate (MTA), ferric sulphate, and sodium hypochlorite (NaOCl) as
      pulp dressing agents in primary molars after 2 years. DESIGN: One hundred primary
      molars requiring pulp treatment were allocated randomly to the control (FC) and
      experimental groups (MTA, ferric sulphate, and NaOCl). Clinical and radiographic
      evaluations were performed at 6, 12, 18, and 24 months. Statistical analysis
      using Fischer's exact test was performed to determine the significant differences
      between groups. RESULTS: In the FC and MTA groups, 100% of the available teeth
      were clinically successful at all follow-up appointments. In the NaOCl group, one
      clinical failure was found at 18 months, and two clinical failures in the ferric
      sulphate group were noted at 12 and 24 months, but no significant differences
      were found among the groups (P = 0.41). No significant differences in
      radiographic success were found among all the groups at 24 months of follow-up (P
      = 0.303). CONCLUSIONS: No statistically significant differences among the four
      materials were found at 24 months suggesting that NaOCl may be an appropriate
      substitute for FC.

PMID- 23171352
TI  - Metabolic engineering of plant monoterpenes, sesquiterpenes and diterpenes-
      current status and future opportunities.
AB  - Terpenoids (a.k.a. isoprenoids) represent the most diverse class of natural
      products found in plants, with tens of thousands of reported structures. Plant
      derived terpenoids have a multitude of pharmaceutical and industrial
      applications, but the natural resources for their extraction are often limited
      and, in many cases, synthetic routes are not commercially viable. Some of the
      most valuable terpenoids are not accumulated in model plants or crops, and
      genetic resources for breeding of terpenoid natural product traits are thus
      poorly developed. At present, metabolic engineering, either in the native
      producer or a heterologous host, is the only realistic alternative to improve
      yield and accessibility. In this review article, we will evaluate the state of
      the art of modulating the biosynthetic pathways for the production of mono-,
      sesqui- and diterpenes in plants.

PMID- 23171353
TI  - Direct imaging of DNA fibers: the visage of double helix.
AB  - Direct imaging becomes important when the knowledge at few/single molecule level
      is requested and where the diffraction does not allow to get structural and
      functional information. Here we report on the direct imaging of double stranded
      (ds) lambda-DNA in the A conformation, obtained by combining a novel sample
      preparation method based on super hydrophobic DNA molecules self-aggregation
      process with transmission electron microscopy (TEM). The experimental
      breakthrough is the production of robust and highly ordered paired DNA nanofibers
      that allowed its direct TEM imaging and the double helix structure revealing.

PMID- 23171354
TI  - Effectiveness of an intervention at construction worksites on work engagement,
      social support, physical workload, and need for recovery: results from a cluster
      randomized controlled trial.
AB  - BACKGROUND: To prolong sustainable healthy working lives of construction workers,
      a worksite prevention program was developed which aimed to improve the health and
      work ability of construction workers. The aim of the current study was to
      investigate the effectiveness of this program on social support at work, work
      engagement, physical workload and need for recovery. METHODS: Fifteen departments
      from six construction companies participated in this cluster randomized
      controlled trial; 8 departments (n=171 workers) were randomized to an
      intervention group and 7 departments (n=122 workers) to a control group. The
      intervention consisted of two individual training sessions of a physical
      therapist to lower the physical workload, a Rest-Break tool to improve the
      balance between work and recovery, and two empowerment training sessions to
      increase the influence of the construction workers at the worksite. Data on work
      engagement, social support at work, physical workload, and need for recovery were
      collected at baseline, and at three, six and 12 months after the start of the
      intervention using questionnaires. RESULTS: No differences between the
      intervention and control group were found for work engagement, social support at
      work, and need for recovery. At 6 months follow-up, the control group reported a
      small but statistically significant reduction of physical workload. CONCLUSION:
      The intervention neither improved social support nor work engagement, nor was it
      effective in reducing the physical workload and need for recovery among
      construction workers. TRIAL REGISTRATION: NTR1278.

PMID- 23171355
TI  - Assessing impacts of land-applied manure from concentrated animal feeding
      operations on fish populations and communities.
AB  - Concentrated animal feeding operation (CAFO) manure is a cost-effective
      fertilizer. In the Midwest, networks of subsurface tile-drains expedite transport
      of animal hormones and nutrients from land-applied CAFO manure to adjacent
      waterways. The objective of this study was to evaluate impacts of land-applied
      CAFO manure on fish populations and communities. Water chemistry including
      hormone, pesticide, and nutrient concentrations was characterized from study
      sites along with fish assemblage structure, growth, and endocrine disruption
      assessed in selected fish species. Although most CAFO water samples had hormone
      concentrations <1 ng/L, equivalent concentrations for 17beta-E2 and 17alpha-TB
      peaked at >30 ng/L each during the period of spawning, hatching, and development
      for resident fishes. CAFO sites had lower fish species richness, and fishes
      exhibited faster somatic growth and lower reproductive condition compared to
      individuals from the reference site. Fathead minnows (Pimephales promelas)
      exposed to CAFO ditchwater during early developmental stages exhibited
      significantly skewed sex ratios toward males. Maximum observed hormone
      concentrations were well above the lowest observable effect concentrations for
      these hormones; however, complexities at the field scale make it difficult to
      directly relate hormone concentration and impacts on fish. Complicating factors
      include the consistent presence of pesticides and nutrients, and the difference
      in temperature and stream architecture of the CAFO-impacted ditches compared to
      the reference site (e.g., channelization, bottom substrate, shallow pools, and
      riparian cover).

PMID- 23171356
TI  - Computer-navigated total knee arthroplasty in haemophilic arthropathy.
AB  - Total knee arthroplasty (TKA) in end-stage haemophilic arthropathy is complex and
      challenging due to the altered bony anatomy, arthrofibrosis and muscle
      contractures. Computer navigation is especially advocated in patients with
      deformity or altered anatomy to improve alignment and to assist in ligament
      balancing. The objective of this study was to evaluate the results of computer
      navigated TKA in haemophilic arthropathy. A consecutive series of computer
      assisted TKA for the end-stage haemophilic arthropathy between February 2007 and
      December 2009 were evaluated. A total of 27 TKA were performed in 25 patients.
      Pre- and postoperative full-length weight-bearing radiographs were assessed for
      the axial limb alignment. The orientation of the components was measured on
      anteroposterior radiographs. Clinically, Knee Society score and Short Form-36
      were evaluated. The mechanical axis of the leg was within a range of +/-3 degrees
      varus/valgus in 92% of the TKA. The coronal alignment of the femoral and tibial
      components was within a range of +/-3 degrees in 96% of the knees. The clinical
      outcomes were significantly improved after the operation. There were no
      complications specific to the computer navigation. Computer-navigated TKA helps
      in restoring the mechanical axis and improves accuracy of orientation of the
      components in patients with end-stage haemophilic arthropathy. Potential benefits
      in long-term outcome require further investigation.

PMID- 23171357
TI  - Does the proliferation fraction help identify mature B cell lymphomas with double
      and triple-hit translocations?
AB  - AIMS: The entity 'B cell lymphoma, unclassifiable, with features intermediate
      between diffuse large B cell lymphoma (DLBCL) and Burkitt lymphoma (BL)' refers
      to B cell neoplasms that share overlapping characteristics of BL and DLBCL. A
      subset of these 'grey-zone lymphomas' possesses C-MYC and IGH translocations but,
      in addition, contains additional rearrangements of BCL2 and/or BCL6 genes. The
      aim of this study was to investigate if the proliferation fraction by Ki67
      immunostaining can be used to identify such double-/triple-hit lymphomas. METHODS
      AND RESULTS: We studied 492 cases of mature aggressive B cell neoplasms by
      histology, immunohistochemistry and interphase fluorescence in-situ hybridization
      (FISH) using break-apart probes against C-MYC, BCL2, BCL6, IGH, MALT1, PAX5 and
      CCND1. Forty Burkitt lymphomas and 28 cases of MYC(+) double-/triple-hit
      lymphomas were identified. Of the latter, 77% and 54% displayed proliferation
      fractions exceeding 75% and 90%, respectively. With a cut-off of >75% by Ki67
      immunostaining, the sensitivity and specificity for detection of MYC(+)
      double/triple translocations was 0.77 and 0.36. Raising the proliferation
      fraction criterion to >90% improved the specificity to 0.62 at the expense of a
      low sensitivity of 0.54. CONCLUSIONS: Immunostaining for Ki67 is not a useful
      approach to prescreen B cell lymphomas for MYC(+) double/triple translocations.

PMID- 23171358
TI  - Dual positivity of hepatitis B surface antigen and anti-hepatitis C virus
      antibody and associated factors among apparently healthy patients of Ekiti State,
      Nigeria.
AB  - There are few studies on health-facility based prevalence rates for dual
      hepatitis B virus-hepatitis C virus (HBV-HCV) infection on a state-wide scale in
      Nigeria. In this study we determined the state-wide prevalence rate of dual
      positivity of hepatitis B surface antigen and anti-HCV antibody among hospital
      patients of Ekiti State, Nigeria, and identified associated factors. Consenting
      apparently-healthy patients visiting health centers in all local government area
      (LGA) headquarters of Ekiti State were consecutively selected to a total of 2000
      individuals. Patient demographic data pertinent to HBV and HCV transmission were
      obtained using a structured questionnaire. Subsequently, serum samples prepared
      from the aseptically collected blood was tested for the presence of both HBsAg
      and anti-HCV antibody using DiaSpot test strips. The results were analyzed using
      binary logistic regression. Dual positivity of 7.40% was recorded among the study
      participants, with 9.80% and 12.80%, respectively, testing positive for HBsAg and
      anti-HCV antibody. The study patients were, however, most likely to be anti-HCV
      antibody positive. Nine of the 10 factors studied were independently associated
      with dual positivity. Five of these, in descending order of odds ratio, were:
      illiteracy (15.76, p=0.001); having >=4 sexual partners (9.46, p=0.001); age
      range of 35-44 y (8.46,p=0.001); farming (7.33, p=0.001); and "not at all" to use
      of condoms during sexual intercourse (4.39, p=0.001). The dual positivity rate
      was relatively high, with unprotected sexual intercourse as the most probable
      mode of acquisition of HBV and HCV by the seropositive study participants.

PMID- 23171359
TI  - A pilot study comparing the development of EIAV Env-specific antibodies induced
      by DNA/recombinant vaccinia-vectored vaccines and an attenuated Chinese EIAV
      vaccine.
AB  - Data from successful attenuated lentiviral vaccine studies indicate that fully
      mature Env-specific antibodies characterized by high titer, high avidity, and the
      predominant recognition of conformational epitopes are associated with protective
      efficacy. Although vaccination with a DNA prime/recombinant vaccinia-vectored
      vaccine boost strategy has been found to be effective in some trials with non
      human primate/simian/human immunodeficiency virus (SHIV) models, it remains
      unclear whether this vaccination strategy could elicit mature equine infectious
      anemia virus (EIAV) Env-specific antibodies, thus protecting vaccinated horses
      against EIAV infection. Therefore, in this pilot study we vaccinated horses using
      a strategy based on DNA prime/recombinant Tiantan vaccinia (rTTV)-vectored
      vaccines encoding EIAV env and gag genes, and observed the development of Env
      specific antibodies, neutralizing antibodies, and p26-specific antibodies.
      Vaccination with DNA induced low titer, low avidity, and the predominant
      recognition of linear epitopes by Env-specific antibodies, which was enhanced by
      boosting vaccinations with rTTV vaccines. However, the maturation levels of Env
      specific antibodies induced by the DNA/rTTV vaccines were significantly lower
      than those induced by the attenuated vaccine EIAV(FDDV). Additionally, DNA/rTTV
      vaccines did not elicit broadly neutralizing antibodies. After challenge with a
      virulent EIAV strain, all of the vaccinees and control horses died from EIAV
      disease. These data indicate that the regimen of DNA prime/rTTV vaccine boost did
      not induce mature Env-specific antibodies, which might have contributed to immune
      protection failure.

PMID- 23171361
TI  - Antiepileptic drug treatment patterns and economic burden of commercially-insured
      patients with refractory epilepsy with partial onset seizures in the United
      States.
AB  - OBJECTIVE: To assess the economic burden in direct healthcare utilization and
      costs for refractory epileptic patients with partial onset seizures (POS) and
      assess the antiepileptic drug (AED) treatment patterns among these patients.
      METHODS: This retrospective database study analyzed administrative claims of
      commercially-insured patients with POS from 2004-2008. Healthcare costs and
      utilization were compared between refractory (defined as >=3 AEDs) and non
      refractory patients by calendar year and AED treatment patterns were described
      for refractory patients. RESULTS: Of the 79,149 patients identified (mean age 33
      years; 54.8% female), 8714 (11%) were classified as refractory. In 2008, average
      annual healthcare costs for refractory patients were significantly higher than
      non-refractory patients ($33,613 vs $19,085), also by settings for inpatient
      ($11,780 vs $6076), outpatient ($13,431 vs $8637), and pharmacy costs ($8402 vs
      $4372) (all p < 0.001). Among refractory patients, close to one-third of total
      costs were for POS-related services. Similar trends were observed when assessing
      POS-related utilization and costs. The differences were consistent across all
      calendar years examined. Among refractory patients, 80.5% were on monotherapy at
      the beginning of the follow-up period. Levetiracetam is the common AED in
      mono/combination therapy as well as add-on/switch-to. LIMITATIONS: The onset of
      seizure cannot be identified, and the indication of each AED could not be
      confirmed from the pharmacy claims. Only direct medical costs were assessed.
      CONCLUSIONS: Pattern of use was very dynamic, suggesting seizures are not well
      controlled. Improving seizure control and reducing economic burden of refractory
      epilepsy remain important unmet medical needs in this population.

PMID- 23171360
TI  - Minocycline-associated rimmed vacuolar myopathy in a patient with rheumatoid
      arthritis.
AB  - BACKGROUND: The autophagic vacuolar myopathies (AVM) are a group of inherited
      myopathies defined by the presence of autophagic vacuoles in pathological muscle
      specimens. AVM can be categorized into three groups: acid maltase deficiency,
      myopathies characterized by autophagic vacuoles with unique sarcolemmal features,
      and rimmed vacuolar myopathies (RVM). While the pathogeneses of these conditions
      are still being elucidated, some drugs (e.g., chloroquine, its analog,
      hydroxychloroquine, and colchicine) can also cause AVM. Minocycline is a disease
      modifying anti-rheumatic drug that may be used in the treatment of rheumatoid
      arthritis (RA). Here, we describe the first case of minocycline-associated AVM
      with rimmed vacuole formation. CASE PRESENTATION: A 75-year-old woman suffering
      from RA has been continuously treated with minocycline (200 mg/day) for the past
      7 years. During this time, she developed a myopathy that predominantly affected
      her lower limbs. Histological studies of biopsied muscle revealed scattered
      atrophic myofibers with rimmed vacuoles that contained pigment granules.
      Histochemical staining revealed that the pigment comprised both iron and melanin,
      which is consistent with type II minocycline-induced cutaneous pigmentation.
      Under electron microscopy, autophagic vacuoles were consistently observed in
      association with numerous collections of pigment granules. CONCLUSIONS: This is
      the first report of minocycline-induced pigmentation in skeletal muscle. The
      strong association between autophagic vacuoles and the accumulation of
      minocycline-induced pigments suggest that long-term minocycline treatment induced
      pigment accumulation, leading to elevation of autophagic activity and RVM. It
      might also be possible that minocycline directly activated autophagy, as the
      observed pigments are known to form complexes containing minocycline and/or its
      metabolites. As long-term minocycline treatment is expected to be used more
      widely in the future, we must draw attention to this adverse effect.

PMID- 23171362
TI  - Association of interleukin-18 promoter polymorphisms with chronic obstructive
      pulmonary disease in male smokers.
AB  - Chronic obstructive pulmonary disease (COPD) is considered a complex genetic
      disorder and it is expected that many genes play a role in the pathogenesis of
      this disease. Previous studies have reported that several variations within the
      interleukin (IL)-18 gene promoter region have been associated with different
      inflammatory diseases such as asthma. However, the association of IL-18 promoter
      polymorphisms with COPD has not been studied yet. We then performed a prospective
      case-control study to explore this association in male smokers of Chinese Han
      people. Our study recruited 112 COPD cases and 105 healthy controls matched for
      age. The genotyping of IL-18 promoter polymorphisms (-607 C/A and -137 G/C) was
      performed using TaqMan single nucleotide polymorphism genotyping assays. The
      frequencies of the alleles and genotypes in patients and controls were compared.
      We found that the frequency of IL-18 -607 C allele was significantly increased in
      patients with COPD (odds ratio (OR) = 1.48, 95% confidence interval (CI) = 1.01
      2.15, P = 0.04). The frequency of IL-18 -607 C allele was significantly higher in
      the GOLD (Global initiative for Obstructive Lung Disease) 3-4 group compared with
      the GOLD 1-2 group (OR=2.06, 95% CI = 1.21-3.51, P = 0.01). There were no
      significant differences in the frequencies of the alleles and genotypes of IL-18 
      137 G/C polymorphism between the patients and healthy smokers or between GOLD 3-4
      group and GOLD 1-2 group. Our study revealed that the IL-18 -607 C/A polymorphism
      was associated with COPD susceptibility and severity of airflow limitation in
      male smokers of Chinese Han people.

PMID- 23171364
TI  - Physician perspectives and compliance with patient advance directives: the role
      external factors play on physician decision making.
AB  - BACKGROUND: Following passage of the Patient Self Determination Act in 1990,
      health care institutions that receive Medicare and Medicaid funding are required
      to inform patients of their right to make their health care preferences known
      through execution of a living will and/or to appoint a surrogate-decision maker.
      We evaluated the impact of external factors and perceived patient preferences on
      physicians' decisions to honor or forgo previously established advance directives
      (ADs). In addition, physician views regarding legal risk, patients' ability to
      comprehend complexities involved with their care, and impact of medical costs
      related to end-of-life care decisions were explored. METHODS: Attendees of two
      Mayo Clinic continuing medical education courses were surveyed. Three scenarios
      based in part on previously court-litigated matters assessed impact of external
      factors and perceived patient preferences on physician compliance with patient
      articulated wishes regarding resuscitation. General questions measured
      respondents' perception of legal risk, concerns over patient knowledge of
      idiosyncrasies involved with their care, and impact medical costs may have on
      compliance with patient preferences. Responses indicating strength of agreement
      or disagreement with statements were treated as ordinal data and analyzed using
      the Cochran Armitage trend test. RESULTS: Three hundred eighty-eight of 951
      surveys were completed (41% response rate). Eighty percent reported they were
      likely to honor a patient's AD despite its 5 year age. Fewer than half (41%)
      would honor the AD of a patient in ventricular fibrillation who had expressed a
      desire to "pass away in peace." Few (17%) would forgo an AD following a family's
      request for continued resuscitative treatment. A majority (52%) considered risk
      of liability to be lower when maintaining someone alive against their wishes than
      mistakenly failing to provide resuscitative efforts. A large percentage (74%)
      disagreed that patients could not appreciate complexities surrounding their care
      while 69% agreed that costs should never impact a physician's decision as to
      whether to comply with a patient's AD. CONCLUSIONS: Our findings highlight the
      impact, albeit small, external factors have on physician AD compliance. Most
      respondents based their decision on the clinical situation at hand and
      interpretation of the patient's initial wishes and preferences expressed by the
      AD.

PMID- 23171363
TI  - Molecular characterization of LMW-GS genes in Brachypodium distachyon L. reveals
      highly conserved Glu-3 loci in Triticum and related species.
AB  - BACKGROUND: Brachypodium distachyon L. is a newly emerging model plant system for
      temperate cereal crop species. However, its grain protein compositions are still
      not clear. In the current study, we carried out a detailed proteomics and
      molecular genetics study on grain glutenin proteins in B. distachyon. RESULTS:
      SDS-PAGE and RP-HPLC analysis of grain proteins showed that Brachypodium has few
      gliadins and high molecular weight glutenin subunits. In contrast the
      electrophoretic patterns for the albumin, globulin and low molecular weight
      glutenin subunit (LMW-GS) fractions of the grain protein were similar to those in
      wheat. In particular, the LMW-C type subunits in Brachypodium were more abundant
      than the equivalent proteins in common wheat. Southern blotting analysis
      confirmed that Brachypodium has 4-5 copies of LMW-GS genes. A total of 18 LMW-GS
      genes were cloned from Brachypodium by allele specific PCR. LMW-GS and 4 deduced
      amino acid sequences were further confirmed by using Western-blotting and MALDI
      TOF-MS. Phylogenetic analysis indicated that Brachypodium was closer to Ae.
      markgrafii and Ae. umbellulata than to T. aestivum. CONCLUSIONS: Brachypodium
      possessed a highly conserved Glu-3 locus that is closely related to Triticum and
      related species. The presence of LMW-GS in B. distachyon grains indicates that B.
      distachyon may be used as a model system for studying wheat quality attributes.

PMID- 23171365
TI  - Experimental and theoretical study on the one- and two-photon absorption
      properties of novel organic molecules based on phenylacetylene and azoaromatic
      moieties.
AB  - This Article reports a combined experimental and theoretical analysis on the one
      and two-photon absorption properties of a novel class of organic molecules with a
      pi-conjugated backbone based on phenylacetylene (JCM874, FD43, and FD48) and
      azoaromatic (YB3p25) moieties. Linear optical properties show that the
      phenylacetylene-based compounds exhibit strong molar absorptivity in the UV and
      high fluorescence quantum yield with lifetimes of approximately 2.0 ns, while the
      azoaromatic-compound has a strong absorption in the visible region with very low
      fluorescence quantum yield. The two-photon absorption was investigated employing
      nonlinear optical techniques and quantum chemical calculations based on the
      response functions formalism within the density functional theory framework. The
      experimental data revealed well-defined 2PA spectra with reasonable cross-section
      values in the visible and IR. Along the nonlinear spectra we observed two 2PA
      allowed bands, as well as the resonance enhancement effect due to the presence of
      one intermediate one-photon allowed state. Quantum chemical calculations revealed
      that the 2PA allowed bands correspond to transitions to states that are also one
      photon allowed, indicating the relaxation of the electric-dipole selection rules.
      Moreover, using the theoretical results, we were able to interpret the
      experimental trends of the 2PA spectra. Finally, using a few-energy-level
      diagram, within the sum-over-essential states approach, we observed strong
      qualitative and quantitative correlation between experimental and theoretical
      results.

PMID- 23171366
TI  - Anomalous reactivity of silylborane: transition-metal-free boryl substitution of
      aryl, alkenyl, and alkyl halides with silylborane/alkoxy base systems.
AB  - An unexpected borylation of organic halides with a silyborane in the presence of
      an alkoxy base has been observed. This formal nucleophilic boryl substitution can
      be applied to a broad range of substrates with high functional group
      compatibility. Even sterically hindered aryl bromides afforded the corresponding
      boryl compounds in high yields. Preliminary mechanistic studies indicated that
      this boryl substitution is promoted by neither transition-metal contamination nor
      a radical-mediated process.

PMID- 23171367
TI  - Models, phases and cases of patient participation in decision-making in surgical
      treatment in Norway: a qualitative study.
AB  - This study improves our understanding of patients' participation in hospital
      treatment-decision processes. We explored the degree of patient participation
      perceived by both patients and healthcare professionals in four phases of the
      decision process: information dissemination, formulation of options, integration
      of information, and control within four models of interactions between healthcare
      professionals and patients: the paternalistic model, the shared model, the
      informed model, and the non-paternalistic model. The analysis was based on 18 in
      depth, exploratory interviews with patients and healthcare professionals in six
      surgical units in Norway. Knowledge about how patients and healthcare
      professionals interact in the surgical-decision process is important for
      developing systems and arenas for patient participation in practice, and for a
      climate and culture to further support the implementation.

PMID- 23171368
TI  - After insufficient radiofrequency ablation, tumor-associated endothelial cells
      exhibit enhanced angiogenesis and promote invasiveness of residual hepatocellular
      carcinoma.
AB  - BACKGROUND: The mechanism regarding rapid progression of residual hepatocellular
      carcinoma (HCC) after insufficient radiofrequency ablation (RFA) has been
      preliminarily discussed. However, most studies have mainly focused on RFA-induced
      changes in the tumor cells. The present study was designed to determine whether
      tumor-associated endothelial cells (TAECs) could contribute to the invasiveness
      of HCC after insufficient RFA. METHODS: TAECs were isolated from fresh HCC tissue
      and characterized. Morphological changes were observed in TAECs after heat
      treatment for 10 min. TAEC proliferation, migration and tube formation after heat
      treatment for 10 min at 37 degrees C (control group), and 42 and 47 degrees C
      (insufficient RFA groups) were examined. The differences in TAECs interactions
      with HepG2-GFP or HCCLM3-GFP cells among the two insufficient RFA groups and
      control group were evaluated. The expression of E-selectin, ICAM-1 and VCAM-1 in
      TAECs was measured. The effects of TAECs on the invasiveness of HepG2-GFP or
      HCCLM3-GFP cells after insufficient RFA were analyzed. The IL-6, IL-8, MCP-1 and
      GRO-alpha concentrations in conditioned medium from TAECs were measured after
      insufficient RFA. The associated signaling pathways of Akt, ERK1/2, STAT3 and NF
      kappaB were analyzed in TAECs after insufficient RFA. RESULTS: TAECs expressed
      the EC-specific markers and took up complexes of Dil-Ac-LDL. Relative to the
      control group, the proliferation of TAECs was significantly inhibited and their
      migration and tube formation were significantly enhanced in the insufficient RFA
      groups. Significantly more HepG2-GFP or HCCLM3-GFP cells adhered to TACEs in
      these groups than in the control group (all P<0.001), via up-regulated expression
      of E-selectin, ICAM-1 and VCAM-1. TAECs promoted the invasiveness of HepG2-GFP or
      HCCLM3-GFP cells after insufficient RFA via the up-regulation of IL-6, IL-8, MCP
      1 and GRO-alpha in conditioned medium (all P<0.05). Insufficient RFA enhanced the
      activities of Akt, ERK1/2 and NF-kappaB signaling pathways and inhibited STAT3
      signaling pathways. CONCLUSIONS: Insufficient RFA enhanced TAEC migration and
      tube formation, and this may play a key role in the rapid growth of residual HCC.
      Increased expression of metastasis-related molecules in TAECs after insufficient
      RFA may be a potential mechanism for the metastasis of residual HCC.

PMID- 23171369
TI  - Social inequalities in life expectancy and mortality during the transition period
      of economic crisis (1993-2010) in Korea.
AB  - BACKGROUNDS: This study examines social inequalities in life expectancy and
      mortality during the transition period of the Korean economic crisis (1993-2010)
      among Korean adults aged 40 and over. METHODS: Data from the census and the
      national death file from the Statistics Korea are employed to calculate life
      expectancy and age-specific-death-rates (ASDR) by age, gender, and educational
      attainment for five years: 1993, 1995, 2000, 2005, and 2010. Absolute and
      relative differences in life expectancy and Age-Specific Death Rates by
      educational attainment were utilized as proxy measures of social inequality.
      RESULTS: Clear educational gradient of life expectancy was observed at age 40 by
      both sexes and across five time periods (1993, 1995, 2000, 2005, and 2010). The
      gradient became notably worse in females between 1993 and 2010 compared to the
      trend in males. The educational gradient was also found for ASDR in all five
      years, but it was more pronounced in working age groups (40s and 50s) than in
      elderly groups. The relative disadvantage of ASDR among working age Korean
      adults, both males and females, became substantially worse over time.
      CONCLUSIONS: Social inequalities in life expectancy and ASDR of the working age
      group across socioeconomic status over time were closely related to the widening
      of the social difference created by the macroeconomic crisis and the expansion of
      neo-liberalism in Korea.

PMID- 23171370
TI  - Surface hybrid self-assembly, mechanism, and crystalline behavior of a carboxyl
      ended hyperbranched polyester/platinum complex.
AB  - The self-assembly of hyperbranched polymers has attracted much attention because
      of their wide application. In this article, we report a new facile surface self
      assembly method for a carboxyl-ended hyperbranched polyester/platinum complex
      (HTD-3-Pt) and obtain ordered structural microrods with a length of 10-20 MUm and
      a width of 1 MUm. The length and diameter of the self-assembled microrods could
      be increased to 300-600 MUm and 4-5 MUm, respectively, by hierarchical self
      assembly. The main factors affecting the morphology of the self-assemblies,
      including temperature, time, solvent and solubility parameter, and relative
      humidity were discussed by transmission/reflection polarizing optical microscopy
      (TRPOM), SEM, and HRSEM. The indications for the coordination bond (-COOPt)
      included the appearance of a new peak at 1606 cm(-1) and its shifting to 1634 cm(
      1) in the FT-IR spectra, the disappearance of the C 1s peak at about 288.6 eV,
      and the increase in the O 1s electron binding energy in the XPS spectra.
      Furthermore, an interesting crystal property of the HTD-3-Pt self-assemblies was
      discovered and confirmed by XRD. The study results from the surface self-assembly
      mechanism suggest that the coordination induction of the platinum ion play a key
      role in driving microphase separation between the intermolecular chains and end
      groups of the HTD-3-Pt to form the microrod self-assemblies. Another interesting
      finding was that HTD-3-Pt showed a higher catalytic activity for hydrosilylation
      than did a traditional homogeneous catalyst.

PMID- 23171371
TI  - A cross-sectional study on cerebrospinal fluid biomarker levels in cognitively
      normal elderly subjects with or without a family history of Alzheimer's disease.
AB  - BACKGROUND: Cerebrospinal fluid (CSF) biomarkers reflect changes in the brain,
      and contribute to early screening. Maternal inheritance is putatively stronger
      than paternal inheritance for late-onset Alzheimer's disease (LOAD). METHODS:
      Clinical data of 162 cognitively normal subjects were reviewed. A standard
      questionnaire was used to identify LOAD family history. Mini-mental state
      examination (MMSE) was used to evaluate cognition. CSF Abeta1-40, Abeta1-42,
      total and phosphorylated tau were measured using ELISA. AIMS: To compare
      biomarkers in cognitively normal elderly subjects with versus without LOAD family
      history. RESULTS: Among the 162 subjects, 38 and 60 had LOAD family history on
      paternal and maternal sides, respectively. The remaining 60 subjects had no
      family history. No difference was noted in age, gender, education level, MMSE
      score, and memory impairment complaint in the three groups. Abeta42 and the
      Abeta42/40 ratio were lower than in subjects with a maternal history than in
      subjects with a paternal history or without family history (P < 0.05 in both).
      Phosphorylated and total tau did not differ among the three groups. CONCLUSION:
      Offspring with a family history of LOAD on the maternal side have lower Abeta42
      and Abeta42/40 ratio in the CSF, and maybe at higher risk for developing AD.

PMID- 23171372
TI  - Transcriptome analysis reveals unique metabolic features in the Cryptosporidium
      parvum Oocysts associated with environmental survival and stresses.
AB  - BACKGROUND: Cryptosporidium parvum is a globally distributed zoonotic parasite
      and an important opportunistic pathogen in immunocompromised patients. Little is
      known on the metabolic dynamics of the parasite, and study is hampered by the
      lack of molecular and genetic tools. Here we report the development of the first
      Agilent microarray for C. parvum (CpArray15K) that covers all predicted ORFs in
      the parasite genome. Global transcriptome analysis using CpArray15K coupled with
      real-time qRT-PCR uncovered a number of unique metabolic features in oocysts, the
      infectious and environmental stage of the parasite. RESULTS: Oocyst stage
      parasites were found to be highly active in protein synthesis, based on the high
      transcript levels of genes associated with ribosome biogenesis, transcription and
      translation. The proteasome and ubiquitin associated components were also highly
      active, implying that oocysts might employ protein degradation pathways to
      recycle amino acids in order to overcome the inability to synthesize amino acids
      de novo. Energy metabolism in oocysts was featured by the highest level of
      expression of lactate dehydrogenase (LDH) gene. We also studied parasite
      responses to UV-irradiation, and observed complex and dynamic regulations of gene
      expression. Notable changes included increased transcript levels of genes
      involved in DNA repair and intracellular trafficking. Among the stress-related
      genes, TCP-1 family members and some thioredoxin-associated genes appear to play
      more important roles in the recovery of UV-induced damages in the oocysts. Our
      observations also suggest that UV irradiation of oocysts results in increased
      activities in cytoskeletal rearrangement and intracellular membrane trafficking.
      CONCLUSIONS: CpArray15K is the first microarray chip developed for C. parvum,
      which provides the Cryptosporidium research community a needed tool to study the
      parasite transcriptome and functional genomics. CpArray15K has been successfully
      used in profiling the gene expressions in the parasite oocysts as well as their
      responses to UV-irradiation. These observations shed light on how the parasite
      oocysts might adapt and respond to the hostile external environment and
      associated stress such as UV irradiation.

PMID- 23171373
TI  - Variation of cats under domestication: genetic assignment of domestic cats to
      breeds and worldwide random-bred populations.
AB  - Both cat breeders and the lay public have interests in the origins of their pets,
      not only in the genetic identity of the purebred individuals, but also in the
      historical origins of common household cats. The cat fancy is a relatively new
      institution with over 85% of its 40-50 breeds arising only in the past 75 years,
      primarily through selection on single-gene aesthetic traits. The short, yet
      intense cat breed history poses a significant challenge to the development of a
      genetic marker-based breed identification strategy. Using different breed
      assignment strategies and methods, 477 cats representing 29 fancy breeds were
      analysed with 38 short tandem repeats, 148 intergenic and five phenotypic single
      nucleotide polymorphisms. Results suggest the frequentist method of Paetkau
      (single nucleotide polymorphisms = 0.78, short tandem repeats = 0.88) surpasses
      the Bayesian method of Rannala and Mountain (single nucleotide polymorphisms =
      0.56, short tandem repeats = 0.83) for accurate assignment of individuals to the
      correct breed. Additionally, a post-assignment verification step with the five
      phenotypic single nucleotide polymorphisms accurately identified between 0.31 and
      0.58 of the misassigned individuals raising the sensitivity of assignment with
      the frequentist method to 0.89 and 0.92 for single nucleotide polymorphisms and
      short tandem repeats respectively. This study provides a novel multistep
      assignment strategy and suggests that, despite their short breed history and
      breed family groupings, a majority of cats can be assigned to their proper breed
      or population of origin, that is, race.

PMID- 23171374
TI  - Rhodium-catalyzed one-pot intermolecular [2 + 2 + 2] trimerization/asymmetric
      intramolecular [4 + 2] cycloaddition of two aryl ethynyl ethers and 5-alkynals.
AB  - It has been established that a cationic Rh(I)/(R)-H(8)-BINAP complex catalyzes
      the one-pot intermolecular [2 + 2 + 2] trimerization/asymmetric intramolecular [4
      + 2] cycloaddition of two aryl ethynyl ethers and 5-alkynals to produce annulated
      1,4-cyclohexadienes possessing two stereogenic centers.

PMID- 23171375
TI  - Increasing sleep duration to lower beat-to-beat blood pressure: a pilot study.
AB  - Strong evidence has accumulated over the last several years, showing that low
      sleep quantity and/or quality plays an important role in the elevation of blood
      pressure. We hypothesized that increasing sleep duration serves as an effective
      behavioral strategy to reduce blood pressure in prehypertension or type 1
      hypertension. Twenty-two participants with prehypertension or stage 1
      hypertension, and habitual sleep durations of 7 h or less, participated in a 6
      week intervention study. Subjects were randomized to a sleep extension group (48
      +/- 12 years, N = 13) aiming to increase bedtime by 1 h daily over a 6-week
      intervention period, or to a sleep maintenance group (47 +/- 12 years, N = 9)
      aiming to maintain habitual bedtimes. Both groups received sleep hygiene
      instructions. Beat-to-beat blood pressure was monitored over 24 h, and 24-h urine
      and a fasting blood sample were collected pre- and post-intervention. Subjects in
      the sleep extension group increased their actigraphy-assessed daily sleep
      duration by 35 +/- 9 min, while subjects in the sleep maintenance condition
      increased slightly by 4 +/- 9 min (P = 0.03 for group effect). Systolic and
      diastolic beat-to-beat blood pressure averaged across the 24-h recording period
      significantly decreased from pre- to post-intervention visit in the sleep
      extension group by 14 +/- 3 and 8 +/- 3 mmHg, respectively (P < 0.05). Though the
      reduction of 7 +/- 5 and 3 +/- 4 mmHg in the sleep maintenance group was not
      significant, it did not differ from the blood pressure reduction in the sleep
      extension group (P = 0.15 for interaction effect). These changes were not
      paralleled by pre- to post-intervention changes in inflammatory or sympatho
      adrenal markers, nor by changes in caloric intake. While these preliminary
      findings have to be interpreted with caution due to the small sample size, they
      encourage future investigations to test whether behavioral interventions designed
      to increase sleep duration serve as an effective strategy in the treatment of
      hypertension.

PMID- 23171376
TI  - Aqueous-biamphiphilic ionic liquid systems: self-assembly and synthesis of gold
      nanocrystals/microplates.
AB  - Biamphiphilic ionic liquids (BAILs) based on 1,3-dialkylimidazolium cation and
      alkyl sulfate anions ([C(n)H(2n+1)mim][C(m)H(2m+1)OSO(3)]; n = 4, 6, or 8; m = 8,
      12) have been synthesized and characterized for their self-assembling behavior in
      the aqueous medium. Effects of alteration of alkyl chain length in cation and
      anion on surfactant properties of BAILs have been examined from surface tension
      measurements. The effectiveness of surface tension reduction for BAILs has been
      found to be exceptionally higher as compared to single chain surface active
      ILs/conventional surfactants. The thermodynamics of the aggregation process has
      been studied using isothermal titration calorimetry (ITC) and temperature
      dependent conductivity experiments. Dynamic light scattering (DLS), nuclear
      magnetic resonance (NMR), and transmission electron microscopy (TEM) studies
      showed that BAILs formed distinct aggregated structures depending upon the
      amphiphilic character present in the cation and anion. BAILs
      ([C(n)H(2n+1)mim][C(m)H(2m+1)OSO(3)]) form micelles when n = 4, 6; m = 8,
      intermicellar aggregates when n = 4, 6; m = 12, and vesicles when n = 8; m = 8,
      12. Gold nanoparticles and microplates have been synthesized in micellar and
      vesicle solutions of BAILs using a simple photoreduction method. The studies show
      the potential of BAILs for constructing micelles and supramolecular assemblies,
      such as bilayer vesicles, which are effective in preparation of nanomaterials of
      controlled size and morphology.

PMID- 23171377
TI  - Deep-sequencing transcriptome analysis of chilling tolerance mechanisms of a
      subnival alpine plant, Chorispora bungeana.
AB  - BACKGROUND: The plant tolerance mechanisms to low temperature have been studied
      extensively in the model plant Arabidopsis at the transcriptional level. However,
      few studies were carried out in plants with strong inherited cold tolerance.
      Chorispora bungeana is a subnival alpine plant possessing strong cold tolerance
      mechanisms. To get a deeper insight into its cold tolerance mechanisms, the
      transcriptome profiles of chilling-treated C. bungeana seedlings were analyzed by
      Illumina deep-sequencing and compared with Arabidopsis. RESULTS: Two cDNA
      libraries constructed from mRNAs of control and chilling-treated seedlings were
      sequenced by Illumina technology. A total of 54,870 unigenes were obtained by de
      novo assembly, and 3,484 chilling up-regulated and 4,571 down-regulated unigenes
      were identified. The expressions of 18 out of top 20 up-regulated unigenes were
      confirmed by qPCR analysis. Functional network analysis of the up-regulated genes
      revealed some common biological processes, including cold responses, and
      molecular functions in C. bungeana and Arabidopsis responding to chilling.
      Karrikins were found as new plant growth regulators involved in chilling
      responses of C. bungeana and Arabidopsis. However, genes involved in cold
      acclimation were enriched in chilling up-regulated genes in Arabidopsis but not
      in C. bungeana. In addition, although transcription activations were stimulated
      in both C. bungeana and Arabidopsis, no CBF putative ortholog was up-regulated in
      C. bungeana while CBF2 and CBF3 were chilling up-regulated in Arabidopsis. On the
      other hand, up-regulated genes related to protein phosphorylation and auto
      ubiquitination processes were over-represented in C. bungeana but not in
      Arabidopsis. CONCLUSIONS: We conducted the first deep-sequencing transcriptome
      profiling and chilling stress regulatory network analysis of C. bungeana, a
      subnival alpine plant with inherited cold tolerance. Comparative transcriptome
      analysis suggests that cold acclimation is not a major chilling tolerance
      mechanism of C. bungeana. Activation of protein phosphorylation and
      ubiquitination may confer chilling tolerance to C. bungeana in a more rapid and
      flexible way than cold acclimation. Such differences may have contributed to the
      differences in cold tolerance between C. bungeana and Arabidopsis. The results
      presented in this paper will be informative for gene discovery and the molecular
      mechanisms related to plant cold tolerance.

PMID- 23171378
TI  - Diversity, distribution and sources of bacteria in residential kitchens.
AB  - Bacteria readily colonize kitchen surfaces, and the exchange of microbes between
      humans and the kitchen environment can impact human health. However, we have a
      limited understanding of the overall diversity of these communities, how they
      differ across surfaces and sources of bacteria to kitchen surfaces. Here we used
      high-throughput sequencing of the 16S rRNA gene to explore biogeographical
      patterns of bacteria across > 80 surfaces within the kitchens of each of four
      households. In total, 34 bacterial and two archaeal phyla were identified, with
      most sequences belonging to the Actinobacteria, Bacteroidetes, Firmicutes and
      Proteobacteria. Genera known to contain common food-borne pathogens were low in
      abundance but broadly distributed throughout the kitchens, with different taxa
      exhibiting distinct distribution patterns. The most diverse communities were
      associated with infrequently cleaned surfaces such as fans above stoves,
      refrigerator/freezer door seals and floors. In contrast, the least diverse
      communities were observed in and around sinks, which were dominated by biofilm
      forming Gram-negative lineages. Community composition was influenced by
      conditions on individual surfaces, usage patterns and dispersal from source
      environments. Human skin was the primary source of bacteria across all kitchen
      surfaces, with contributions from food and faucet water dominating in a few
      specific locations. This study demonstrates that diverse bacterial communities
      are widely distributed in residential kitchens and that the composition of these
      communities is often predictable. These results also illustrate the ease with
      which human- and food-associated bacteria can be transferred in residential
      settings to kitchen surfaces.

PMID- 23171379
TI  - Does maternal depression predict young children's executive function? - a 4-year
      longitudinal study.
AB  - BACKGROUND: Building on reports that parental maltreatment and neglect adversely
      affect young children's executive function (EF), this longitudinal study examined
      whether exposure to a more common risk factor, mothers' depressive symptoms,
      predicted individual differences in EF at school-age. METHODS: We followed up at
      age 6 a socially diverse sample of 126 children (78 boys, 48 girls) for whom
      direct observations of mother-child interactions have been shown to predict gains
      in EF between the ages of 2 and 4. We used an EF latent factor based on scores
      from three tasks (Beads, Day/Night, Tower of London) that tapped working memory,
      inhibitory control and planning, as well as a latent growth model of mothers'
      Beck Depression Inventory factor scores at four time-points, and included age 6
      verbal ability as a covariate in all analyses. RESULTS: The intercept and slope
      for mothers' depressive symptoms each predicted unique variance in EF at age 6;
      these predictive effects remained significant when we also included: (a) age 2
      working memory, (b) maternal education and (c) direct observations of maternal
      positive control at ages 2 and 6. CONCLUSION: Our findings suggest that early
      exposure to mothers' depressive symptoms adversely affects children's developing
      EF, and that the chronicity of this exposure may matter.

PMID- 23171381
TI  - Obesity and C-reactive protein in various populations: a systematic review and
      meta-analysis.
AB  - Obesity has been associated with elevated levels of C-reactive protein (CRP), a
      marker of inflammation and predictor of cardiovascular risk. The objective of
      this systematic review and meta-analysis was to estimate the associations between
      obesity and CRP according to sex, ethnicity and age. MEDLINE and EMBASE databases
      were searched through October 2011. Data from 51 cross-sectional studies that
      used body mass index (BMI), waist circumference (WC) or waist-to-hip ratio (WHR)
      as measure of obesity were independently extracted by two reviewers and
      aggregated using random-effects models. The Pearson correlation (r) for BMI and
      ln(CRP) was 0.36 (95% confidence interval [CI], 0.30-0.42) in adults and 0.37
      (CI, 0.31-0.43) in children. In adults, r for BMI and ln(CRP) was greater in
      women than men by 0.24 (CI, 0.09-0.37), and greater in North Americans/Europeans
      than Asians by 0.15 (CI, 0-0.28), on average. In North American/European
      children, the sex difference in r for BMI and ln(CRP) was 0.01 (CI, -0.08 to
      0.06). Although limited to anthropometric measures, we found similar results when
      WC and WHR were used in the analyses. Obesity is associated with elevated levels
      of CRP and the association is stronger in women and North Americans/Europeans.
      The sex difference only emerges in adulthood.

PMID- 23171382
TI  - Congenital von Willebrand's disease and clinical hypothyroidism.
AB  - Data from case reports and systematic reviews suggest an association of
      Hypothyroidism and Acquired von Willebrand's syndrome. It is not known if
      congenital von Willebrand's disease is associated with hypothyroidism in a
      similar way. The aim of this study was to identify the association of congenital
      von Willebrand's disease (VWD) with clinical hypothyroidism. A total of 350 cases
      of congenital VWD were initially screened from our institution database from 1985
      to 2010. A careful review of patient records was carried out to see if patients
      truly had congenital VWD and coexisting clinical hypothyroidism. Patients with
      uncertain diagnoses or other bleeding disorders were excluded, leading to 197
      patients remaining in the final sample. A random age- and sex-matched parallel
      control group was also obtained from the hospital database. Of 197 patients (mean
      age 43.8 +/- 17.5 years, women 72%) of congenital VWD, 32/197 (16%) were
      diagnosed with clinical hypothyroidism, while only 11/197 (5.6%) of the matched
      controls were clinically hypothyroid. Univariate and multivariate analysis
      demonstrated that VWD was an independent predictor of developing clinical
      hypothyroidism (OR 3.45; 95% CI 1.65-7.22, P = 0.001). The proportion of patients
      diagnosed with clinical hypothyroidism was more in the VWD group (P < 0.0001).
      Our analysis shows a strong association of clinical hypothyroidism in patients
      with congenital VWD, but future studies will be required to delineate a
      pathological mechanism. In our opinion, clinicians should consider checking
      thyroid function in the newly diagnosed and established cases of congenital VWD.

PMID- 23171380
TI  - The effects of a rhythm and music-based therapy program and therapeutic riding in
      late recovery phase following stroke: a study protocol for a three-armed
      randomized controlled trial.
AB  - BACKGROUND: Stroke represents one of the most costly and long-term disabling
      conditions in adulthood worldwide and there is a need to determine the
      effectiveness of rehabilitation programs in the late phase after stroke. Limited
      scientific support exists for training incorporating rhythm and music as well as
      therapeutic riding and well-designed trials to determine the effectiveness of
      these treatment modalities are warranted. METHODS/DESIGN: A single blinded three
      armed randomized controlled trial is described with the aim to evaluate whether
      it is possible to improve the overall health status and functioning of
      individuals in the late phase of stroke (1-5 years after stroke) through a rhythm
      and music-based therapy program or therapeutic riding. About 120 individuals will
      be consecutively and randomly allocated to one of three groups: (T1) rhythm and
      music-based therapy program; (T2) therapeutic riding; or (T3) control group
      receiving the T1 training program a year later. Evaluation is conducted prior to
      and after the 12-week long intervention as well as three and six months later.
      The evaluation comprises a comprehensive functional and cognitive assessment
      (both qualitative and quantitative), and questionnaires. Based on the
      International classification of functioning, disability, and health (ICF), the
      outcome measures are classified into six comprehensive domains, with
      participation as the primary outcome measure assessed by the Stroke Impact Scale
      (SIS, version 2.0.). The secondary outcome measures are grouped within the
      following domains: body function, activity, environmental factors and personal
      factors. Life satisfaction and health related quality of life constitute an
      additional domain. CURRENT STATUS: A total of 84 participants were randomised and
      have completed the intervention. Recruitment proceeds and follow-up is on-going,
      trial results are expected in early 2014. DISCUSSION: This study will ascertain
      whether any of the two intervention programs can improve overall health status
      and functioning in the late phase of stroke. A positive outcome would increase
      the scientific basis for the use of such interventions in the late phase after
      stroke. TRIAL REGISTRATION: Clinical Trials.gov Identifier: NCT01372059.

PMID- 23171383
TI  - A cluster randomised trial of a school-based resilience intervention to decrease
      tobacco, alcohol and illicit drug use in secondary school students: study
      protocol.
AB  - BACKGROUND: Whilst schools provide a potentially appropriate setting for
      preventing substance use among young people, systematic review evidence suggests
      that past interventions in this setting have demonstrated limited effectiveness
      in preventing tobacco, alcohol and other drug use. Interventions that adopt a
      mental wellbeing approach to prevent substance use offer considerable promise and
      resilience theory provides one method to impact on adolescent mental well-being.
      The aim of the proposed study is to examine the efficacy of a resilience
      intervention in decreasing the tobacco, alcohol and illicit drug use of
      adolescents. METHODS: A cluster randomised controlled trial with schools as the
      unit of randomisation will be undertaken. Thirty two schools in disadvantaged
      areas will be allocated to either an intervention or a control group. A
      comprehensive resilience intervention will be implemented, inclusive of explicit
      program adoption strategies. Baseline surveys will be conducted with students in
      Grade 7 in both groups and again three years later when the student cohort is in
      Grade 10. The primary outcome measures will include self-reported tobacco,
      alcohol, marijuana and other illicit drug use. Comparisons will be made post-test
      between Grade 10 students in intervention and control schools to determine
      intervention effectiveness across all measures. DISCUSSION: To the authors'
      knowledge this is the first randomised controlled trial to evaluate the
      effectiveness of a comprehensive school-based resilience intervention, inclusive
      of explicit adoption strategies, in decreasing tobacco, alcohol and illicit drug
      use of adolescents attending disadvantaged secondary schools. TRIAL REGISTRATION:
      ACTRN12611000606987.

PMID- 23171384
TI  - Elevated CO2 does not offset greater water stress predicted under climate change
      for native and exotic riparian plants.
AB  - In semiarid western North American riparian ecosystems, increased drought and
      lower streamflows under climate change may reduce plant growth and recruitment,
      and favor drought-tolerant exotic species over mesic native species. We tested
      whether elevated atmospheric CO2 might ameliorate these effects by improving
      plant water-use efficiency. We examined the effects of CO2 and water availability
      on seedlings of two native (Populus deltoides spp. monilifera, Salix exigua) and
      three exotic (Elaeagnus angustifolia, Tamarix spp., Ulmus pumila) western North
      American riparian species in a CO2-controlled glasshouse, using 1-m-deep pots
      with different water-table decline rates. Low water availability reduced seedling
      biomass by 70-97%, and hindered the native species more than the exotics.
      Elevated CO2 increased biomass by 15%, with similar effects on natives and
      exotics. Elevated CO2 increased intrinsic water-use efficiency (Delta13C(leaf) ),
      but did not increase biomass more in drier treatments than wetter treatments. The
      moderate positive effects of elevated CO2 on riparian seedlings are unlikely to
      counteract the large negative effects of increased aridity projected under
      climate change. Our results suggest that increased aridity will reduce riparian
      seedling growth despite elevated CO2, and will reduce growth more for native
      Salix and Populus than for drought-tolerant exotic species.

PMID- 23171385
TI  - Performance of risk estimation for hepatocellular carcinoma in chronic hepatitis
      B (REACH-B) score in classifying treatment eligibility under 2012 Asian Pacific
      Association for the Study of the Liver (APASL) guideline for chronic hepatitis B
      patients.
AB  - BACKGROUND: REACH-B [Risk Estimation for Hepatocellular Carcinoma (HCC) in
      Chronic Hepatitis B] scoring system was developed to predict the risk of HCC in
      noncirrhotic chronic hepatitis B (CHB) patients. AIM: To evaluate the
      discriminatory performance of REACH-B scoring system in classifying anti-viral
      treatment eligibility of CHB patients according to the 2012 Asian Pacific
      Association for the Study of the Liver (APASL) treatment guideline. METHODS: A
      total of 904 noncirrhotic CHB were enrolled. Patients' age, gender, liver
      biochemistry, HBeAg status and HBV DNA levels were recorded. RESULTS: The minimum
      REACH-B risk score for patients to be eligible for anti-viral treatment was 7 for
      HBeAg-positive and 6 for HBeAg-negative patients. Among them, increasing REACH-B
      score was not significantly associated with eligibility for treatment [adjusted
      odds ratio (OR): 1.210, 95% confidence interval (CI): 0.979-1.494, P = 0.078] in
      HBeAg-positive patients, as shown by logistic regression analysis after adjusting
      for gender. In HBeAg-negative patients, REACH-B score significantly predicted the
      treatment eligibility (adjusted OR: 1.783, 95% CI: 1.607-1.979, P < 0.001).
      Discriminatory ability of REACH-B score to classify eligibility was poor for
      HBeAg-positive patients >=40 years [area under receiver operating characteristic
      (AUC): 0.664, 95% CI: 0.533-0.795], but good/excellent for HBeAg-positive
      patients <40 years (AUC: 0.903; 95% CI: 0.841-0.964), HBeAg-negative patients
      >=45 years (AUC: 0.883; 95% CI: 0.848-0.917) and HBeAg-negative patients <45
      years (AUC: 0.907; 95% CI: 0.874-0.940). CONCLUSION: The discriminatory
      performance of the REACH-B scoring system in classifying anti-viral treatment
      eligibility based on the 2012 APASL guideline was good/excellent, except for >=40
      years old HBeAg-positive patients.

PMID- 23171386
TI  - From silence to storm--patient illness trajectory from diabetes diagnosis to
      haemodialysis in Taiwan: a qualitative study of patients' perceptions.
AB  - AIMS: This article is a report of a study that explored the perceptions of
      patients as they experienced their diabetes illness trajectory, and their initial
      decisions to undergo dialysis, in an effort to provide further complementary
      guidance for nurses and healthcare practitioners. BACKGROUND: Diabetes leads to
      higher morbidity and mortality when patients develop renal failure resulting from
      diabetic nephropathy. An effective self-care regimen and multidisciplinary team
      approach are required to avoid or delay the serious chronic complications of the
      disease. Patients and healthcare practitioners must be aware therefore of psycho
      physiological adjustment when seeking to delay the onset of complications.
      DESIGN: A qualitative design was used for data collection through semi-structured
      interviews. METHOD: Data were analysed using content analysis. Participants were
      25 diabetes patients undergoing initial haemodialysis who were recruited from
      diabetes and nephrology wards at a medical centre in northern Taiwan. Data were
      collected from December 2010-August 2011. FINDINGS: The core theme describing the
      illness trajectory derived from face-to-face interviews with people undergoing
      hemodialysis was 'from silence to storm'. There emerged also five phases of
      patient experience that resulted from the development of diabetic nephropathy:
      (1) diabetes onset stage; (2) stable stage; (3) burden stage; (4) shock stage;
      and (5) coping stage. CONCLUSIONS: Patients suffer with diabetic nephropathy for
      a long-term period. Our findings may enhance the understanding of nurses
      regarding the experiences of patients with diabetic nephropathy, and will help
      them provide diabetes care that promotes healthy life for those individuals.

PMID- 23171387
TI  - Factors influencing adolescents' oral health-related quality of life (OHRQoL).
AB  - BACKGROUND: OHRQoL comprises an apparently complex array of biological and
      psychological aspects of oral health. AIM: To determine the relative contribution
      of sociodemographic, psychosocial, or clinical characteristics to OHRQoL in
      adolescents. DESIGN: A cross-sectional study of Dunedin adolescents was carried
      out. Each participant completed a self-administered questionnaire and underwent a
      clinical examination. Information collected included sociodemographic
      characteristics (sex, ethnicity, and household deprivation), psychosocial
      characteristics (self-esteem, psychological well-being, somatisation, and self
      perception scores for body image), and clinical measures (DMFS and Dental
      Aesthetic Index). OHRQoL was measured using the 16-item impact short-form CPQ11
      14 questionnaire. Linear regression analyses used the CPQ11-14 as the dependent
      variable, with independent variables entered in related groups. RESULTS: Three
      hundred and fifty-three children (48.4% females) took part, representing a 58.8%
      response rate. Linear regression modelling of the CPQ11-14 score showed that
      sociodemographic characteristics were predictors, but the model's overall
      explanatory power was low (R(2) = 0.05). This increased slightly with inclusion
      of the clinical variables. When the psychosocial variables were added, however,
      the R(2) increased to 0.50; all psychosocial variables (except self-esteem) were
      strongly associated with the CPQ11-14 score. Psychological well-being was the
      strongest predictor. CONCLUSION: Psychosocial characteristics are important
      contributors to OHRQoL in adolescents and appear to be more important than
      sociodemographic or clinical characteristics.

PMID- 23171388
TI  - Battlefield compassion and posttraumatic growth in combat servicepersons.
AB  - The literature is replete with studies related to the negative outcomes of
      serving in combat. However, for some military servicepersons, healing could be
      assisted by understanding the positive experiences and outcomes related to combat
      service. This study surveyed 59 servicepersons to identify acts of battlefield
      compassion, as well as other positive military experiences. In addition,
      participants were asked to identify personal changes as a result of compassionate
      experiences and to give an overall rating of their time in combat. Results are
      compared to the posttraumatic growth (PTG) literature and reveal that
      participants identified positive changes associated with experiences of
      compassion.

PMID- 23171389
TI  - Health-related quality of life among Latinos with multiple sclerosis.
AB  - This study identifies characteristics associated with health-related quality of
      life (HRQOL) among Latinos with multiple sclerosis (MS). Data were collected from
      99 Latinos with MS, with multiple linear regression models utilized to analyze
      these data. Marital status, MS symptoms, depressive symptoms, treatment at MS
      clinics, and satisfaction with insurance coverage of MS-related care were
      significantly linked with physical HRQOL. Marital status, employment, access to
      MS-focused care, and need for mental health care were significantly associated
      with mental health dimensions of HRQOL. Identifying characteristics associated
      with better HRQOL among Latinos with MS should facilitate approaches that address
      the health needs of this community.

PMID- 23171390
TI  - Arab mothers' involvement with their offspring with severe intellectual
      disabilities after placement in institutional care.
AB  - This study examines the cognitive-behavioral and emotional involvement among 81
      Israeli Arab mothers after placement of their offspring with severe intellectual
      disabilities in institutional care, with respect to mothers' and offspring's
      background data and measures of divisional roles in the Arab family. Core
      findings indicate that the most important predictors of maternal cognitive and
      behavioral involvement are the existence of psychiatric disability in addition to
      intellectual disability, and the offspring's duration of stay in institutional
      care. These predictors were poorer in explaining maternal emotional involvement.
      Findings are interpreted with respect to social work research and practice with
      Israeli Arab families.

PMID- 23171391
TI  - The relationship between environment, efficacy beliefs, and academic achievement
      of low-income African American children in special education.
AB  - African American students are overrepresented in special education. Ecological
      systems theory, social cognitive theory, and a literature review demonstrate that
      children's environments, particularly school, and self-efficacy impact the
      educational outcomes of African American children. Interventions have aimed to
      improve children's environmental resources and efficacy. The aim of this study
      was to assess the impact of environment, efficacy beliefs, and the Nurse-Family
      Partnership intervention on the educational achievements of African American
      children in special education. A secondary data analysis of 126 African American
      children in special education found that self-efficacy and the number of hours
      spent in special education were associated with their academic achievement.

PMID- 23171393
TI  - Novel and distinct metabolites identified following a single oral dose of alpha-
      or gamma-hexabromocyclododecane in mice.
AB  - The metabolism of alpha- and gamma-hexabromocyclododecane (HBCD) was investigated
      in adult C57BL/6 female mice. alpha- or gamma-[(14)C]HBCD (3 mg/kg bw) was orally
      administered with subsequent urine and feces collection for 4 consecutive days; a
      separate group of mice was dosed and sacrificed 3 h postexposure to investigate
      tissue metabolite levels. Extractable and nonextractable HBCD metabolites were
      quantitated in liver, blood, fat, brain, bile, urine, and feces and characterized
      by LC/MS (ESI-). Metabolites identified were distinct between the two
      stereoisomers. In mice exposed to alpha-HBCD, four hydroxylated metabolites were
      detected in fecal extracts, and one of these metabolite isomers was consistently
      characterized in liver, brain, and adipose tissue extracts. In contrast, fecal
      extracts from mice exposed to gamma-HBCD contained multiple isomers of
      monohydroxy-pentabromocyclododecene, dihydroxy-pentabromocyclododecene, and
      dihydroxy-pentabromocyclododecadiene, while in liver and adipose tissues extracts
      only a single monohydroxy-pentabromocyclododecane metabolite was observed. Both
      stereoisomers were transformed to metabolites which formed covalent bonds to
      proteins and/or lipids in the gut as suggested by high fecal nonextractables. The
      presence of tissue- and excreta-specific metabolic products after in vivo
      exposure to the two main HBCD stereoisomers supports previous toxicokinetic
      studies indicating that these two stereoisomers are biologically distinct. The
      distinct metabolic products identified in this study have the potential to aid in
      the identification of stereoisomer-specific HBCD exposures in future
      biomonitoring studies.

PMID- 23171394
TI  - Motivating medical information system performance by system quality, service
      quality, and job satisfaction for evidence-based practice.
AB  - BACKGROUND: No previous studies have addressed the integrated relationships among
      system quality, service quality, job satisfaction, and system performance; this
      study attempts to bridge such a gap with evidence-based practice study. METHODS:
      The convenience sampling method was applied to the information system users of
      three hospitals in southern Taiwan. A total of 500 copies of questionnaires were
      distributed, and 283 returned copies were valid, suggesting a valid response rate
      of 56.6%. SPSS 17.0 and AMOS 17.0 (structural equation modeling) statistical
      software packages were used for data analysis and processing. RESULTS: The
      findings are as follows: System quality has a positive influence on service
      quality (gamma11= 0.55), job satisfaction (gamma21= 0.32), and system performance
      (gamma31= 0.47). Service quality (beta31= 0.38) and job satisfaction (beta32=
      0.46) will positively influence system performance. CONCLUSIONS: It is thus
      recommended that the information office of hospitals and developers take
      enhancement of service quality and user satisfaction into consideration in
      addition to placing b on system quality and information quality when designing,
      developing, or purchasing an information system, in order to improve benefits and
      gain more achievements generated by hospital information systems.

PMID- 23171395
TI  - Marital power process of Korean men married to foreign women: a qualitative
      study.
AB  - This study explored how Korean men married to migrant women construct meaning
      around married life. Data were collected through in-depth interviews with 10 men
      who had had been married to migrant women for >= 2 years. Data collection and
      analysis were performed concurrently using a grounded theory approach. The core
      category generated was the process of sustaining a family unit. The men came to
      understand the importance of a distribution of power within the family in
      sustaining the family unit. Constituting this process were four stages:
      recognizing an imbalance of power, relinquishing power, empowering, and fine
      tuning the balance of power. This study provides important insight into the
      dynamics of marital power from men's point of view by demonstrating a link
      between the way people adjust to married life and the process by which married
      couples adjust through the distribution and redistribution of power.

PMID- 23171396
TI  - Highly enantioselective Rh-catalyzed carboacylation of olefins: efficient
      syntheses of chiral poly-fused rings.
AB  - Here we report the first highly enantioselective Rh-catalyzed carboacylation of
      olefins via C-C bond activation of benzocyclobutenones. Good yields and excellent
      enantioselectivities (92-99% ee, 14 examples) were obtained for substrates with
      various steric and electronic properties. In addition, fully saturated poly-fused
      rings were prepared from the carboacylation products through a challenging
      catalytic reductive dearomatization approach. These investigations provide a
      distinct way to prepare chiral carbon frameworks that are nontrivial to access
      with conventional methods.

PMID- 23171399
TI  - Through bond energy transfer: a convenient and universal strategy toward
      efficient ratiometric fluorescent probe for bioimaging applications.
AB  - Fluorescence resonance energy transfer (FRET) strategy has been widely applied in
      designing ratiometric probes for bioimaging applications. Unfortunately, for FRET
      systems, sufficiently large spectral overlap is necessary between the donor
      emission and the acceptor absorption, which would limit the resolution of double
      channel images. The through-bond energy transfer (TBET) system does not need
      spectral overlap between donor and acceptor and could afford large wavelength
      difference between the two emissions with improved imaging resolution and higher
      energy transfer efficiency than that of the classical FRET system. It seems to be
      more favorable for designing ratiometric probes for bioimaging applications. In
      this paper, we have designed and synthesized a coumarin-rhodamine (CR) TBET
      system and demonstrated that TBET is a convenient strategy to design an efficient
      ratiometric fluorescent bioimaging probe for metal ions. Such TBET strategy is
      also universal, since no spectral overlap between the donor and the acceptor is
      necessary, and many more dye pairs than that of FRET could be chosen for probe
      design. As a proof-of-concept, Hg(2+) was chosen as a model metal ion. By
      combining TBET strategy with dual-switch design, the proposed sensing platform
      shows two well-separated emission peaks with a wavelength difference of 110 nm,
      high energy transfer efficiency, and a large signal-to-background ratio, which
      affords a high sensitivity for the probe with a detection limit of 7 nM for
      Hg(2+). Moreover, by employing an Hg(2+)-promoted desulfurization reaction as
      recognition unit, the probe also shows a high selectivity to Hg(2+). All these
      unique features make it particularly favorable for ratiometric Hg(2+) sensing and
      bioimaging applications. It has been preliminarily used for a ratiometric image
      of Hg(2+) in living cells and practical detection of Hg(2+) in river water
      samples with satisfying results.

PMID- 23171398
TI  - De novo characterization of the Chinese fir (Cunninghamia lanceolata)
      transcriptome and analysis of candidate genes involved in cellulose and lignin
      biosynthesis.
AB  - BACKGROUND: Chinese fir (Cunninghamia lanceolata) is an important timber species
      that accounts for 20-30% of the total commercial timber production in China.
      However, the available genomic information of Chinese fir is limited, and this
      severely encumbers functional genomic analysis and molecular breeding in Chinese
      fir. Recently, major advances in transcriptome sequencing have provided fast and
      cost-effective approaches to generate large expression datasets that have proven
      to be powerful tools to profile the transcriptomes of non-model organisms with
      undetermined genomes. RESULTS: In this study, the transcriptomes of nine tissues
      from Chinese fir were analyzed using the Illumina HiSeqTM 2000 sequencing
      platform. Approximately 40 million paired-end reads were obtained, generating
      3.62 gigabase pairs of sequencing data. These reads were assembled into 83,248
      unique sequences (i.e. Unigenes) with an average length of 449 bp, amounting to
      37.40 Mb. A total of 73,779 Unigenes were supported by more than 5 reads, 42,663
      (57.83%) had homologs in the NCBI non-redundant and Swiss-Prot protein databases,
      corresponding to 27,224 unique protein entries. Of these Unigenes, 16,750 were
      assigned to Gene Ontology classes, and 14,877 were clustered into orthologous
      groups. A total of 21,689 (29.40%) were mapped to 119 pathways by BLAST
      comparison against the Kyoto Encyclopedia of Genes and Genomes (KEGG) database.
      The majority of the genes encoding the enzymes in the biosynthetic pathways of
      cellulose and lignin were identified in the Unigene dataset by targeted searches
      of their annotations. And a number of candidate Chinese fir genes in the two
      metabolic pathways were discovered firstly. Eighteen genes related to cellulose
      and lignin biosynthesis were cloned for experimental validating of transcriptome
      data. Overall 49 Unigenes, covering different regions of these selected genes,
      were found by alignment. Their expression patterns in different tissues were
      analyzed by qRT-PCR to explore their putative functions. CONCLUSIONS: A
      substantial fraction of transcript sequences was obtained from the deep
      sequencing of Chinese fir. The assembled Unigene dataset was used to discover
      candidate genes of cellulose and lignin biosynthesis. This transcriptome dataset
      will provide a comprehensive sequence resource for molecular genetics research of
      C. lanceolata.

PMID- 23171400
TI  - The molecular characterization of a catalase from Chinese mitten crab Eriocheir
      sinensis.
AB  - Catalase (CAT) is an antioxidant enzyme and plays a significant role in the
      protection against oxidative stress by reducing hydrogen peroxide. The CAT cDNA
      of Eriocheir sinensis (EsCAT) was cloned via RACE technique. The complete
      sequence of EsCAT cDNA consisted of a 5' untranslated regions (UTR) of 224 bp, a
      3' UTR of 1287 bp with a poly (A) tail and an open reading frame (ORF) of 1542
      bp, which encoded a polypeptide of 513 amino acid residues with a calculated
      molecular mass of approximately 58.86 kDa and a theoretical isoelectric point of
      6.880. The deduced amino acid sequence of EsCAT contained a highly conserved
      proximal active-site signature motif ((60)FDRERIPERVVHAKGAL(76)) and a proximal
      heme-ligand signature motif ((350)RLFSYNDTH(358)) and exhibited high similarity
      with other reported CATs. In the phylogenetic tree, EsCAT was clustered with the
      CATs from Scylla serrata and Portunus trituberculatus. The EsCAT transcripts were
      constitutively expressed in haepatopancreas, haemocytes, gill, gonad, muscle and
      heart, with highest expression level in haepatopancreas. The relative expression
      level of EsCAT mRNA in haemocytes was continuously up-regulated and reached the
      peak level at 48 h post-Vibrio anguillarum challenge. The purified recombinant
      EsCAT protein displayed antioxidant activity against hydrogen peroxide with high
      thermal stability and broad spectrum of pH values. All these results demonstrated
      that EsCAT was an efficient antioxidant enzyme and potentially involved in the
      regulation of redox and innate immune response of crabs.

PMID- 23171397
TI  - Exogenous endothelial cells as accelerators of hematopoietic reconstitution.
AB  - Despite the successes of recombinant hematopoietic-stimulatory factors at
      accelerating bone marrow reconstitution and shortening the neutropenic period
      post-transplantation, significant challenges remain such as cost, inability to
      reconstitute thrombocytic lineages, and lack of efficacy in conditions such as
      aplastic anemia. A possible means of accelerating hematopoietic reconstitution
      would be administration of cells capable of secreting hematopoietic growth
      factors. Advantages of this approach would include: a) ability to regulate
      secretion of cytokines based on biological need; b) long term, localized
      production of growth factors, alleviating need for systemic administration of
      factors that possess unintended adverse effects; and c) potential to actively
      repair the hematopoietic stem cell niche. Here we overview the field of
      hematopoietic growth factors, discuss previous experiences with mesenchymal stem
      cells (MSC) in accelerating hematopoiesis, and conclude by putting forth the
      rationale of utilizing exogenous endothelial cells as a novel cellular therapy
      for acceleration of hematopoietic recovery.

PMID- 23171401
TI  - The gamma-secretase blocker DAPT reduces the permeability of the blood-brain
      barrier by decreasing the ubiquitination and degradation of occludin during
      permanent brain ischemia.
AB  - BACKGROUND: Tight junction protein degradation is a principal characteristic of
      the blood-brain barrier (BBB) damage that occurs during brain ischemia. AIMS: We
      investigated the mechanisms of occludin degradation that underlie permanent
      middle cerebral artery occlusion (pMCAO) in rats. METHODS AND RESULTS: Western
      blot and Co-immunoprecipitation data indicated ubiquitination and degradation of
      occludin in brain after pMCAO, which was consistent with ZO-1 degradation in
      penumbra regions as observed at 24 h after pMCAO. We further investigated
      candidate protease(s) responsible for the degradation of occludin during pMCAO.
      The intraventricular administration of gamma-secretase blocker DAPT significantly
      inhibited the pMCAO-induced neurovascular damage, whereas ALLM and Batimastat,
      which are inhibitors of calpain and metalloproteinase proteases, respectively,
      were less effective. Notably, we found that DAPT significantly inhibited BBB
      disruption in comparison with vehicle treatment, as assessed by Evans blue
      excretion. Interestingly, the confocal immunostaining revealed that activation of
      the E3 ubiquitin ligase Itch is associated with degradation of occludin in brain
      microvessels following ischemia. Furthermore, our data demonstrate that the
      inhibition of gamma-secretase signaling and the itch-mediated ubiquitination of
      occludin likely underlie the vasoprotective effect of DAPT after pMCAO.
      CONCLUSION: The gamma-secretase blocker DAPT reduces the permeability of the BBB
      by decreasing the ubiquitination and degradation of occludin during permanent
      brain ischemia, suggesting that gamma-secretase may represent a novel therapeutic
      target for preventing neurovascular damage.

PMID- 23171402
TI  - Block copolymer-quantum dot micelles for multienzyme colocalization.
AB  - To mimic the structure and functionality of multienzyme complexes, which are
      widely present in Nature, Pluronic-based micelles were designed to colocalize
      multiple enzymes. To stabilize the micelles as well as to enable characterization
      of single enzyme immobilization and multienzyme colocalization by Forster
      resonance energy transfer (FRET), quantum dots (QDs) were incorporated into the
      micelles to form Pluronic-QD micelles using a novel microreactor. Model enzymes
      glucose oxidase (GOX) and horseradish peroxidase (HRP) were respectively labeled
      with fluorescent dyes. The results indicated that FRET occurred between the QDs
      and dyes that labeled each type of enzyme in single enzyme immobilization studies
      as well as between the dyes in colocalization studies. These observations were
      consistent with increases in micelle size after adsorption of dye-enzymes as
      verified by dynamic light scattering. In addition, the activity of single enzymes
      was retained after immobilization. An optimized colocalization process improved
      the overall conversion rate by approximately 100% compared to equivalent
      concentrations of free enzymes in solution. This study demonstrates a versatile
      platform for multienzyme colocalization and an effective strategy to characterize
      multienzyme immobilization and colocalization, which can be applicable to many
      other multienzyme systems.

PMID- 23171403
TI  - In situ chemistry and microbial community compositions in five deep-sea
      hydrothermal fluid samples from Irina II in the Logatchev field.
AB  - We present data on the co-registered geochemistry (in situ mass spectrometry) and
      microbiology (pyrosequencing of 16S rRNA genes; V1, V2, V3 regions) in five fluid
      samples from Irina II in the Logatchev hydrothermal field. Two samples were
      collected over 24 min from the same spot and further three samples were from
      spatially distinct locations (20 cm, 3 m and the overlaying plume). Four low
      temperature hydrothermal fluids from the Irina II are composed of the same core
      bacterial community, namely specific Gammaproteobacteria and
      Epsilonproteobacteria, which, however, differs in the relative abundance. The
      microbial composition of the fifth sample (plume) is considerably different.
      Although a significant correlation between sulfide enrichment and proportions of
      Sulfurovum (Epsilonproteobacteria) was found, no other significant linkages
      between abiotic factors, i.e. temperature, hydrogen, methane, sulfide and oxygen,
      and bacterial lineages were evident. Intriguingly, bacterial community
      compositions of some time series samples from the same spot were significantly
      more similar to a sample collected 20 cm away than to each other. Although this
      finding is based on three single samples only, it provides first hints that
      single hydrothermal fluid samples collected on a small spatial scale may also
      reflect unrecognized temporal variability. However, further studies are required
      to support this hypothesis.

PMID- 23171404
TI  - Can itch-related visual stimuli alone provoke a scratch response in healthy
      individuals?
AB  - BACKGROUND: The sensation of itch and the scratch response elicited by
      application of histamine are enhanced by itch-related visual cues in people with
      existing skin conditions and, to a lesser extent, in healthy controls.
      OBJECTIVES:  We tested whether visual cues alone could generate feelings of itch
      and provoke a scratch response in healthy volunteers. A secondary aim was to
      assess whether the content of some pictures evoked these sensations more
      effectively. METHODS:  Thirty participants viewed static images that were either
      itch-related (e.g. ants, fleas or skin conditions) or neutral (e.g. butterflies
      or healthy skin). These were further separated by picture type into 'skin
      contact' (e.g. ants crawling on the hand or a butterfly on a finger), 'skin
      response' (e.g. scratching an insect bite or washing the hands) or 'context only'
      (e.g. viewing midges or birds flying). RESULTS:  The sensation of itch was
      successfully generated using itch-related pictures, with higher self-reports of
      itch in answer to the questions 'How itchy do you feel?' and 'How itchy do you
      think the person in the picture feels?', compared with viewing neutral pictures
      (P<0.001), and these measures correlated (P<= 0.003). Participants also scratched
      themselves more when viewing itch-related pictures than when viewing neutral ones
      (P<0.001). The interaction with picture type was significant, with more
      scratching behaviour recorded when viewing pictures depicting others scratching
      (P=0.01). CONCLUSIONS:   This study demonstrates the impact of visual cues in
      eliciting sensations of itch and provoking a scratch response, and may provide
      behavioural evidence linking contagious itch to the mirror neuron system.

PMID- 23171405
TI  - Water adsorption at two unsolvated peptides with a protonated lysine residue:
      from self-solvation to solvation.
AB  - We study the initial steps of the interaction of water molecules with two
      unsolvated peptides: Ac-Ala(5)-LysH(+) and Ac-Ala(8)-LysH(+). Each peptide has
      two primary candidate sites for water adsorption near the C-terminus: a
      protonated carboxyl group and the protonated ammonium group of LysH(+), which is
      fully hydrogen-bonded (self-solvated) in the absence of water. Earlier
      experimental studies have shown that H(2)O adsorbs readily at Ac-Ala(5)-LysH(+)
      (a non-helical peptide) but with a much lower propensity at Ac-Ala(8)-LysH(+) (a
      helix) under the same conditions. The helical conformation of Ac-Ala(8)-LysH(+)
      has been suggested as the origin of the different behavior. We here use first
      principles conformational searches (all-electron density functional theory based
      on a van der Waals corrected version of the PBE functional, PBE+vdW) to study the
      microsolvation of Ac-Ala(5)-LysH(+) with one to five water molecules and the
      monohydration of Ac-Ala(8)-LysH(+). In both cases, the most favorable water
      adsorption sites break intramolecular hydrogen bonds associated with the ammonium
      group, in contrast to earlier suggestions in the literature. A simple
      thermodynamic model yields Gibbs free energies DeltaG(0)(T) and equilibrium
      constants in agreement with experiments. A qualitative change of the first
      adsorption site does not occur. For few water molecules, we do not consider
      carboxyl deprotonation or finite-temperature dynamics, but in a liquid solvent,
      both effects would be important. Exploratory ab initio molecular dynamics
      simulations illustrate the short-time effects of a droplet of 152 water molecules
      on the initial unsolvated conformation, including the deprotonation of the
      carboxyl group. The self-solvation of the ammonium group by intramolecular
      hydrogen bonds is lifted in favor of a solvation by water.

PMID- 23171406
TI  - Approaches to integrated monitoring for environmental health impact assessment.
AB  - Although Integrated Environmental Health Monitoring (IEHM) is considered an
      essential tool to better understand complex environmental health issues, there is
      no consensus on how to develop such a programme. We reviewed four existing
      frameworks and eight monitoring programmes in the area of environmental health.
      We identified the DPSEEA (Driving Force-Pressure-State-Exposure-Effect-Action)
      framework as most suitable for developing an IEHM programme for environmental
      health impact assessment. Our review showed that most of the existing monitoring
      programmes have been designed for specific purposes, resulting in narrow scope
      and limited number of parameters. This therefore limits their relevance for
      studying complex environmental health topics. Other challenges include limited
      spatial and temporal data availability, limited development of data sharing
      mechanisms, heterogeneous data quality, a lack of adequate methodologies to link
      disparate data sources, and low level of interdisciplinary cooperation. To
      overcome some of these challenges, we propose a DPSEEA-based conceptual framework
      for an IEHM programme that would enable monitoring and measuring the impact of
      environmental changes on human health. We define IEHM as 'a systemic process to
      measure, analyse and interpret the state and changes of natural-eco-anthropogenic
      systems and its related health impact over time at the same location with
      causative explanations across the various compartments of the cause-effect
      chain'. We develop a structural work process to integrate information that is
      based on existing environmental health monitoring programmes. Such a framework
      allows the development of combined monitoring systems that exhibit a large degree
      of compatibility between countries and regions.

PMID- 23171407
TI  - Screening of UV-B-induced genes from apple peels by SSH: possible involvement of
      MdCOP1-mediated signaling cascade genes in anthocyanin accumulation.
AB  - Suppression subtractive hybridization (SSH) was employed to identify candidate
      genes involved in red coloration in apple peel with the ultraviolet (UV)-B
      treated 'Mutsu'. After reverse Northern blotting verification, nearly 80 clones
      were successfully sequenced. Large portions of the expressed sequence tags (ESTs)
      are well characterized anthocyanin biosynthesis-related genes, such as chalcone
      synthase (11A5), flavonol synthase (12F3), anthocyanidin synthase (11H5) and UDP
      glycosyl transferase (14A12) whose presence proved the success of SSH. Eight ESTs
      were selected for quantitative real-time polymerase chain reaction analysis and
      their expressions were all elevated in 'Induction', further confirming the
      reliability of the SSH library. One EST, 11F4 (CONSTITUTIVE PHOTOMORPHOGENIC 1:
      COP1) with putative function in light signal relay was further analyzed in
      'Mutsu' and 'Tsugaru', along with MdHY5 (ELONGATED HYPOCOTYL 5: the downstream
      target of COP1), MdMYB22 (a possible flavonol-specific activator under the
      regulation of HY5, belonging to the SG7/PRODUCTION OF FLAVONOL GLYCOSIDES family)
      and MdMYBA. Results showed that MdCOP1, MdHY5, MdMYB22 and MdMYBA were all UV-B
      inducible genes and anthocyanin accumulation occurred after their increased
      expressions. Moreover, their expressions and anthocyanin content were enhanced
      under UV-B plus 17 degrees C treatment. The presence of G box, a known consensus
      binding site of HY5, in the MdMYBA promoter region implicated that it could be
      regulated by MdHY5, which was verified by the result of the yeast one-hybrid
      analysis. Our data suggested that UV-B irradiation would induce the utmost
      upstream light signaling factor, MdCOP1, which activates MdHY5 signaling by
      binding to the promoter regions of MdMYBs, and finally leads to the red
      coloration of apple peels.

PMID- 23171411
TI  - Benzazoles from aliphatic amines and o-amino/mercaptan/hydroxyanilines: elemental
      sulfur as a highly efficient and traceless oxidizing agent.
AB  - A novel remarkably simple solvent-free and catalyst-free synthesis of benzazoles
      from alkylamines and o-hydroxy/amino/mercaptan anilines using elemental sulfur as
      traceless oxidizing agent has been developed.

PMID- 23171413
TI  - Children's understandings and motivations surrounding novelty sweets: a
      qualitative study.
AB  - BACKGROUND: Novelty sweets resemble or can be used as toys, are brightly
      coloured, with striking imagery, and sold at pocket money prices. They encourage
      regular consumption as packaging can be resealed, leading to prolonged exposure
      of these high-sugar and low pH products to the oral tissues, risk factors for
      dental caries and erosion, respectively. AIM: To determine how children
      conceptualise novelty sweets and their motivations for buying and consuming them.
      DESIGN: Focus groups conducted using a brief schedule of open-ended questions,
      supported by novelty sweets used as prompts in the latter stages. Participants
      were school children (aged 9-10) from purposively selected state primary schools
      in Cardiff, UK. RESULTS: Key findings related to the routine nature of sweet
      eating; familiarity with and availability of novelty sweets; parental awareness
      and control; lack of awareness of health consequences; and the overall appeal of
      novelty sweets. CONCLUSIONS: Parents reported vagueness regarding consumption
      habits and permissiveness about any limits they set may have diluted the concept
      of treats. Flexible permissiveness to sweet buying applied to sweets of all
      kinds. Parents' reported lack of familiarity with novelty sweets combined with
      their low cost, easy availability, high sugar content, and acidity give cause for
      concern.

PMID- 23171412
TI  - Concerted suppression of all starch branching enzyme genes in barley produces
      amylose-only starch granules.
AB  - BACKGROUND: Starch is stored in higher plants as granules composed of semi
      crystalline amylopectin and amorphous amylose. Starch granules provide energy for
      the plant during dark periods and for germination of seeds and tubers. Dietary
      starch is also a highly glycemic carbohydrate being degraded to glucose and
      rapidly absorbed in the small intestine. But a portion of dietary starch, termed
      "resistant starch" (RS) escapes digestion and reaches the large intestine, where
      it is fermented by colonic bacteria producing short chain fatty acids (SCFA)
      which are linked to several health benefits. The RS is preferentially derived
      from amylose, which can be increased by suppressing amylopectin synthesis by
      silencing of starch branching enzymes (SBEs). However all the previous works
      attempting the production of high RS crops resulted in only partly increased
      amylose-content and/or significant yield loss. RESULTS: In this study we invented
      a new method for silencing of multiple genes. Using a chimeric RNAi hairpin we
      simultaneously suppressed all genes coding for starch branching enzymes (SBE I,
      SBE IIa, SBE IIb) in barley (Hordeum vulgare L.), resulting in production of
      amylose-only starch granules in the endosperm. This trait was segregating 3:1.
      Amylose-only starch granules were irregularly shaped and showed peculiar thermal
      properties and crystallinity. Transgenic lines retained high-yield possibly due
      to a pleiotropic upregualtion of other starch biosynthetic genes compensating the
      SBEs loss. For gelatinized starch, a very high content of RS (65 %) was observed,
      which is 2.2-fold higher than control (29%). The amylose-only grains germinated
      with same frequency as control grains. However, initial growth was delayed in
      young plants. CONCLUSIONS: This is the first time that pure amylose has been
      generated with high yield in a living organism. This was achieved by a new method
      of simultaneous suppression of the entire complement of genes encoding starch
      branching enzymes. We demonstrate that amylopectin is not essential for starch
      granule crystallinity and integrity. However the slower initial growth of shoots
      from amylose-only grains may be due to an important physiological role played by
      amylopectin ordered crystallinity for rapid starch remobilization explaining the
      broad conservation in the plant kingdom of the amylopectin structure.

PMID- 23171414
TI  - Effects of cumulative sleep restriction on self-perceptions while multitasking.
AB  - This study addressed a rarely studied question of self-perceptions of performance
      and overall functional state during cumulative sleep restriction and the ensuing
      recovery period. Twenty healthy male volunteers, aged 19-29 years, were divided
      into a sleep restriction group (n = 13) and a control group (n = 7). On the first
      2 nights, the sleep restriction group had an 8-h sleep opportunity that was
      restricted to 4 h for the next 5 nights, and then restored to 8 h for the last 2
      nights. The control group had an 8-h sleep opportunity each night. Each day
      participants accomplished 50-min multitask sessions and gave self-ratings in
      their connection. Similar to our previous findings on multitasking performance,
      self-perceived task performance, sleepiness and mental fatigue impaired during
      the sleep restriction and returned to baseline during the recovery phase. Self
      perceived mental effort, tension, task difficulty and task pace showed no
      sensitivity to the sleep restriction. We concluded that sleep-restricted
      individuals can probably make use of some self-perceptions when assessing their
      'fitness for duty'. However, at the individual level these measures seem to be
      inaccurate in revealing actual performance impairments.

PMID- 23171415
TI  - VCT clinic HIV burden and its link with HIV care clinic at the University of
      Gondar hospital.
AB  - BACKGROUND: Voluntary Counselling and Testing (VCT) is an important component of
      any HIV/AIDS control and prevention activities. VCT makes people aware of their
      HIV serostatus and enables early identification of those who need care. It is an
      important link to HIV care and support. The main aim of this study is to describe
      the HIV burden at VCT and define the relationship between the VCT Center and the
      HIV Chronic Care Clinic of the University of Gondar (UoG) Hospital. METHODS: It
      is a record based descriptive study undertaken by using data collected by health
      professionals at the VCT center and the HIV chronic care clinic of the UoG
      Hospital. Patient data collected from 2005/06 to 2008/09 was investigated.
      Analysis was carried out using the SPSS version 16.0. RESULTS: A total of 19,168
      people were tested for HIV and a prevalence of 25.4% was obtained. 4298 HIV
      positive people were referred to the HIV chronic care clinic but only 27%
      actually registered at the clinic. Chi-square analyses showed residence, age and
      time of VCT visit showed significant relations with hospital care attendance.
      CONCLUSION: The overall HIV prevalence is high. The data obtained at the HIV care
      clinic regarding patients' clinical conditions at acceptance were incomplete.
      Improvements are required on the link between VCT and HIV care and documentation
      of data.

PMID- 23171416
TI  - The possibility of regulating for obesity prevention--understanding regulation in
      the Commonwealth Government.
AB  - A complex regulatory package is likely to be necessary to effectively reduce
      obesity prevalence in developed countries. This study investigated the barriers
      and facilitators to implementing regulatory interventions to prevent obesity
      within the executive arm of the Australian Commonwealth Government. Policy
      reviews were conducted on nine government departments to understand their roles
      and interests in obesity. From this process we identified regulatory review
      carried out by the Office of Best Practice Regulation as possibly posing a
      barrier to law reform for obesity prevention, along with the complexity of the
      food policymaking structures. The policy reviews informed subsequent in-depth
      semi-structured interviews with senior Commonwealth government officers (n = 13)
      focused on refining our understanding of the barriers to enacting obesity
      prevention policy. In addition to the two barriers already identified,
      interviewees identified a lack of evidence for interventions, which would reduce
      obesity prevalence, and the influence of politicians on executive decisions as
      posing obstacles. Most interviewees believed that the barriers to regulating to
      prevent obesity were strong and that intervention by elected politicians would be
      the most likely method of implementing obesity prevention policy.

PMID- 23171417
TI  - User fee exemptions and excessive household spending for normal delivery in
      Burkina Faso: the need for careful implementation.
AB  - BACKGROUND: In 2006, the Parliament of Burkina Faso passed a policy to reduce the
      direct costs of obstetric services and neonatal care in the country's health
      centres, aiming to lower the country's high national maternal mortality and
      morbidity rates. Implementation was via a "partial exemption" covering 80% of the
      costs. In 2008 the German NGO HELP launched a pilot project in two health
      districts to eliminate the remaining 20% of user fees. Regardless of any
      exemptions, women giving birth in Burkina Faso's health centres face additional
      expenses that often represent an additional barrier to accessing health services.
      We compared the total cost of giving birth in health centres offering partial
      exemption versus those with full exemption to assess the impact on additional out
      of-pocket fees. METHODS: A case-control study was performed to compare medical
      expenses. Case subjects were women who gave birth in 12 health centres located in
      the Dori and Sebba districts, where HELP provided full fee exemption for
      obstetric services and neonatal care. Controls were from six health centres in
      the neighbouring Djibo district where a partial fee exemption was in place. A
      random sample of approximately 50 women per health centre was selected for a
      total of 870 women. RESULTS: There was an implementation gap regarding the full
      exemption for obstetric services and neonatal care. Only 1.1% of the sample from
      Sebba but 17.5% of the group from Dori had excessive spending on birth related
      costs, indicating that women who delivered in Sebba were much less exposed to
      excessive medical expenses than women from Dori. Additional out-of-pocket fees in
      the full exemption health districts took into account household ability to pay,
      with poorer women generally paying less. CONCLUSIONS: We found that the
      elimination of fees for facility-based births benefits especially the poorest
      households. The existence of excessive spending related to direct costs of giving
      birth is of concern, making it urgent for the government to remove all direct
      fees for obstetric and neonatal care. However, the policy of completely
      abolishing user fees is insufficient; the implementation process must have a
      thorough monitoring system to reduce implementation gaps.

PMID- 23171418
TI  - Male mating performance and cytoplasmic incompatibility in a wPip Wolbachia trans
      infected line of Aedes albopictus (Stegomyia albopicta).
AB  - Wolbachia pipientis Hertig (Rickettsiales: Rickettsiaceae) is a maternally
      inherited endosymbiont of a large number of insects and other arthropods that
      induces various effects on host reproductive biology. Among these, cytoplasmic
      incompatibility (CI) is a form of sterility induced in eggs produced by mating
      between infected males and females uninfected or infected by an incompatible
      Wolbachia strain. This phenomenon has been proposed as a potential way to produce
      functionally sterile males to be used in genetic control programmes. In this
      paper, we report on experiments carried out to evaluate the mating performances
      of males of an Aedes albopictus (Stegomyia albopicta) (Diptera: Culicidae) line
      (ARwP), harbouring a new Wolbachia infection [the wPip strain from Culex pipiens
      Linnaeus (Diptera: Culicidae)], in comparison with naturally infected males (SR
      line). ARwP males did not differ from SR males with regard to insemination
      capacity. Mating competitiveness did not differ significantly between lines in
      either laboratory or greenhouse conditions. Moreover, crosses with SR females
      were characterized by a 100% CI regardless of ARwP male age. All of these
      findings suggest that ARwP males may represent a very efficient tool for control
      programmes against Ae. albopictus based on the release of functionally sterile
      males. 

PMID- 23171419
TI  - Effects of green tea extract and alpha-tocopherol on the lipid oxidation rate of
      omega-3 oils, incorporated into table spreads, prepared using multiple emulsion
      technology.
AB  - This study examined the effectiveness of fat and water soluble antioxidants on
      the oxidative stability of omega (omega)-3 rich table spreads, produced using
      novel multiple emulsion technology. Table spreads were produced by dispersing an
      oil-in-water (O/W) emulsion (500 g/kg 85 camelina/15 fish oil blend) in a
      hardstock/rapeseed oil blend, using sodium caseinate and polyglycerol
      polyricinoleate as emulsifiers. The O/W and oil-in-water-in-oil (O/W/O) emulsions
      contained either a water soluble antioxidant (green tea extract [GTE]), an oil
      soluble antioxidant (alpha-Tocopherol), or both. Spreads containing alpha
      Tocopherol had the highest lipid hydroperoxide values, whereas spreads containing
      GTE had the lowest (P < 0.05), during storage at 5 degrees C, while p-Anisidine
      values did not differ significantly. Particle size was generally unaffected by
      antioxidant type (P < 0.05). Double emulsion (O/W/O) structures were clearly seen
      in confocal images of the spreads. By the end of storage, none of the spreads had
      significantly different G' values. Firmness (Newtons) of all spreads generally
      increased during storage (P < 0.05).

PMID- 23171420
TI  - Deposition of aggregated nanoparticles--a theoretical and experimental study on
      the effect of aggregation state on the affinity between nanoparticles and a
      collector surface.
AB  - Theoretical and experimental approaches were employed to study the effect of
      aggregation on the affinity between nanoparticles (NPs) and a flat surface that
      is quantified by the attachment efficiency. Computer simulations were used to
      generate virtual aggregates formed via either diffusion limited cluster
      aggregation or reaction limited cluster aggregation. The colloidal interactions
      between the simulated aggregates and a flat surface were evaluated based on the
      surface element integration approach. It was found that the strength of colloidal
      interaction for the aggregated NPs was on the same order of magnitude as those
      for the primary particles and was significantly weaker than that for an
      equivalent sphere defined by the gyration radius of the aggregate. The results
      from the deposition experiments using quartz crystal microbalance suggested that
      the attachment efficiencies (unfavorable deposition) for aggregated NPs were
      higher at the initial stage but later became similar to that of the primary NPs
      when equilibrium deposition was reached. The high initial affinity was postulated
      to be attributable to secondary minimum deposition. These results suggest that it
      is the size of the primary particles, not that of the aggregates, that determines
      the strength of the colloidal interaction between the aggregate and an
      environmental surface.

PMID- 23171421
TI  - Prospective memory tasks: a more sensitive method for screening cognitive
      impairment in ALS?
AB  - BACKGROUND: Cognitive change is prevalent in patients with amyotrophic lateral
      sclerosis (ALS), but still lack a widely accepted and sensitive screening method.
      In this study, we try to find a sensitive screening battery for detecting subtle
      cognitive deficits in patients with ALS. METHODS: Eighty consecutive ALS patients
      and 57 matched normal controls underwent the Mini-Mental Status Examination
      (MMSE), the verbal fluency test (VFT), the Stroop Color Word Interference Test
      (CWT), and the prospective memory (PM) tests, including event-based (EBPM) and
      time-based (TBPM). RESULTS: The patients did not differ from the controls in the
      MMSE, the VFT and the CWT. By contrast, statistically significant differences
      were found in the PM tests (EBPM: P=0.043; TBPM: P<0.001). More interestingly,
      TBPM was more sensitive than EBPM in the early-phase patients. CONCLUSIONS:
      Prefrontal lobar dysfunction does exist among ALS patients and may spread from
      the medial to the lateral region. The PM tests seem more sensitive in ALS
      patients with frontotemporal dysfunction than are the classical cognitive
      measures.

PMID- 23171422
TI  - Chronic renoprotective effect of pulsatile perfusion machine RM3 and IGL-1
      solution in a preclinical kidney transplantation model.
AB  - BACKGROUND: Machine perfusion (MP) of kidney graft provides benefits against
      preservation injury, however decreased graft quality requires optimization of the
      method. We examined the chronic benefits of MP on kidney grafts and the potential
      improvements provided by IGL-1 solution. METHOD: We used an established
      autotransplantation pig kidney model to study the effects of MP against the
      deleterious effects of warm ischemia (WI: 60 minutes) followed by 22 hours of
      cold ischemia in MP or static cold storage (CS) followed by autotransplantation.
      MPS and IGL-1 solutions were compared. RESULTS: Animal survival was higher in MPS
      MP and both IGL groups. Creatinine measurement did not discriminate between the
      groups, however MPS-MP and both IGL groups showed decreased proteinuria. Chronic
      fibrosis level was equivalent between the groups. RTqPCR and
      immunohistofluorescent evaluation showed that MP and IGL-1 provided some
      protection against epithelial to mesenchymal transition and chronic lesions. IGL
      1 was protective with both MP and CS, particularly against chronic inflammation,
      with only small differences between the groups. CONCLUSION: IGL-1 used in either
      machine or static preservation offers similar levels of protection than standard
      MP. The compatibility of IGL-1 with both machine perfusion and static storage
      could represent an advantage for clinical teams when choosing the correct
      solution to use for multi-organ collection. The path towards improving machine
      perfusion, and organ quality, may involve the optimization of the solution and
      the correct use of colloids.

PMID- 23171423
TI  - Menopausal symptoms and physical activity in multiethnic groups of midlife women:
      a secondary analysis.
AB  - AIMS: To explore the effect of diverse types of women's physical activity on
      menopausal symptoms among multiethnic groups of midlife women in the USA.
      BACKGROUND: Although physical activity is one of the most widely used non
      pharmacological methods for managing menopausal symptoms, there is a paucity of
      clinical guidelines for women and healthcare providers because the relationship
      between physical activity and menopausal symptoms has been found inconsistent in
      previous studies. DESIGN: A secondary analysis of the data from a lager Internet
      survey study conducted in 2008-2010. METHODS: A total of 481 midlife women among
      four ethnic groups were selected from the original study. The data were collected
      using the Kaiser Physical Activity Survey and the Midlife Women's Symptom Index.
      Bivariate correlation analyses and hierarchical multiple regression analyses were
      used to analyse the data. RESULTS/FINDINGS: The household/caregiving activity
      index was positively associated with the prevalence scores of the psychological
      symptoms in both non-Hispanic Asians and non-Hispanic African Americans. The
      increased sports/exercise activity index was negatively associated with the
      severity scores of the physical symptoms in both Hispanics and non-Hispanic
      Whites. The occupational activity index and the active living activity index
      significantly predicted the severity scores of the psychosomatic symptoms in
      Hispanics and non-Hispanic African Americans, respectively. CONCLUSION: Nurses
      who take care of multiethnic groups of midlife women who experience menopausal
      symptoms should be aware of diverse types of women's physical activities within
      the cultural context.

PMID- 23171425
TI  - Re: Key questions in vitamin D research.

PMID- 23171424
TI  - The mycobacterial binuclear iron monooxygenases require a specific chaperonin
      like protein for functional expression in a heterologous host.
AB  - The mimABCD gene clusters in Mycobacterium smegmatis strain mc(2) 155 and
      Mycobacterium goodii strain 12523 encode binuclear iron monooxygenases that
      oxidize propane and phenol. In this study, we attempted to express each mimABCD
      gene cluster in a heterologous host. The actinomycetous strain Rhodococcus opacus
      B-4, which is phylogenetically close to Mycobacterium, was selected as the host.
      Each mimABCD gene cluster was cloned into the Rhodococcus-Escherichia coli
      shuttle vector, pTip-QC2, and then introduced into R. opacus cells. Although
      whole-cell assays were performed with phenol as a substrate, the transformed R.
      opacus cells did not oxidize this substrate. SDS/PAGE analysis revealed that the
      oxygenase large subunit MimA was expressed in the insoluble fraction of R. opacus
      cells. We found that a gene designated mimG, which lies downstream of mimABCD,
      exhibits similarity in the amino acid sequence of its product with the products
      of genes encoding the chaperonin GroEL. When the mimG gene was cloned and
      coexpressed with each mimABCD gene cluster in R. opacus strain B-4, this host
      successfully acquired oxidation activity towards phenol. SDS/PAGE and western
      blotting analyses demonstrated that MimA was clearly soluble when in the presence
      of MimG. These results indicated that MimG played essential roles in the
      productive folding of MimA, and that the resulting soluble MimA protein led to
      the active expression of MimABCD.

PMID- 23171426
TI  - Prolidase enzyme activity in varicose venous walls related to sperm count in
      patients with varicocele.
AB  - OBJECTIVES: To investigate peripheral, seminal and varicose venous wall prolidase
      enzyme activities and their relationships between sperm parameters in patients
      with varicocele. DESIGN AND METHODS: Prolidase enzyme activities were determined
      in blood, seminal fluid and varicose vein walls in patients with grade 3
      varicocele. Sperm parameters were also measured and the relationships between
      prolidase enzyme and sperm parameters were assessed by statistical correlation
      analysis. RESULTS: There was a significant and negative correlation between sperm
      counts and varicose venous wall prolidase enzyme activities (r = -0.618, p <
      0.001) and a positive significant correlation between sperm counts and seminal
      fluid prolidase enzyme activities (r = 0.676, p < 0.001). None of the parameters
      were correlated with sperm motility indices. CONCLUSION: Varicose venous wall
      prolidase enzyme activity could be an important factor in progression of
      azoospermia and infertility in patients with varicocele.

PMID- 23171427
TI  - Lack of transferability between different immunoassays and LC-MS/MS for total 25
      hydroxyvitamin D measurement and disagreement defining deficiency.
AB  - BACKGROUND: Over the last few years, it has become much more common to measure
      concentrations of vitamin D, as its deficiency has been associated with an
      increasing number of health problems. Recently, a number of new immunoassays for
      measurement of total 25-hydroxyvitamin D (25OH-D) concentration have been
      released but their results may not be transferable. METHODS: Our main objective
      was to compare results from the Cobas((r)) e411 (Roche Diagnostics), Advia
      Centaur((r)) (Siemens), Architect (Abbott), IDS-iSYS (Vitro S.A.), and
      Liaison((r)) (Diasorin) immunoassay systems with each other and with liquid
      chromatography-tandem mass spectrometry (LC-MS/MS). We obtained 184 routine serum
      samples, covering the whole measuring range, for these methods. RESULTS: Kappa
      values above 0.8 were considered to indicate excellent agreement. With a cut-off
      of 50 nmol/L Architect and Cobas were the only immunoassay methods able to
      identify patients with deficiencies consistent with the findings of the reference
      method LC-MS/MS. On the other hand, using a cut-off of 37.5 nmol/L for Liaison
      and 75 nmol/L for IDS-iSYS, while maintaining the value of 50 nmol/L for the LC
      MS/MS method, kappa values of 0.80 and 0.83 respectively were obtained.
      CONCLUSIONS: Choosing the best method for each laboratory is challenging due to
      methodological differences between them and 50 nmol/L cannot be considered as a
      general cut-off for defining hypovitaminosis.

PMID- 23171428
TI  - Physical activity is associated with decreased global DNA methylation in Swedish
      older individuals.

PMID- 23171429
TI  - Successful treatment with thalidomide of a patient with congenital factor V
      deficiency and factor V inhibitor with recurrent gastrointestinal bleeding from
      small bowel arteriovenous malformations.

PMID- 23171431
TI  - Energetic study of cardioplegic hearts under ischaemia/reperfusion and [Ca(2+)]
      changes in cardiomyocytes of guinea-pig: mitochondrial role.
AB  - AIM: To study the role of mitochondria in the recovery of guinea-pig hearts
      exposed to high-K(+)-cardioplegia (CPG) and ischaemia/reperfusion (I/R) METHODS:
      We measured contractility and heat release in perfused guinea-pig hearts and
      cytosolic and mitochondrial Ca(2+) by epifluorescence and confocal microscopy in
      isolated cardiomyocytes loaded with Fluo-4 or Rhod-2. RESULTS: In hearts, CPG
      increased the postischaemic contractile recovery, and this was potentiated by the
      mNCX blocker clonazepam and the mKATP opener diazoxide, which also prevented the
      fall in muscle economy. Moreover, CPG prevented the stunning induced by ouabain,
      which was reduced by clonazepam. In cardiomyocytes, CPG increased fluorescent
      signals of cytosolic and mitochondrial Ca(2+), while the addition of a mNCX
      blocker (CGP37157) increased cytosolic but reduced mitochondrial [Ca(2+)].
      Ouabain in CPG increased cytosolic Ca(2+) and resting heat, but the addition of
      CGP37157 reduced them, as well as mitochondrial Ca(2+). CONCLUSIONS: CPG,
      diazoxide and clonazepam improve postischaemic recovery, respectively, by
      increasing the Ca(2+) cycling and by reducing the mitochondrial Ca(2+) uptake
      either by uniporter or by mNCX. The mitochondria compete with the leaky
      sarcoplasmic reticulum (SR) as sink of Ca(2+) in guinea-pig hearts, affecting the
      postischaemic contractility. CPG also prevented the ouabain-induced dysfunction
      by avoiding the Ca(2+) overload. Ouabain reduced the synergism between CPG and
      clonazepam suggesting that [Na(+)]i and SR load influence the mNCX role.

PMID- 23171430
TI  - Exon capture and bulk segregant analysis:  rapid discovery of causative mutations
      using high-throughput sequencing.
AB  - BACKGROUND: Exome sequencing has transformed human genetic analysis and may do
      the same for other vertebrate model systems. However, a major challenge is
      sifting through the large number of sequence variants to identify the causative
      mutation for a given phenotype. In models like Xenopus tropicalis, an incomplete
      and occasionally incorrect genome assembly compounds this problem. To facilitate
      cloning of X. tropicalis mutants identified in forward genetic screens, we sought
      to combine bulk segregant analysis and exome sequencing into a single step.
      RESULTS: Here we report the first use of exon capture sequencing to identify
      mutations in a non-mammalian, vertebrate model. We demonstrate that bulk
      segregant analysis coupled with exon capture sequencing is not only able to
      identify causative mutations but can also generate linkage information,
      facilitate the assembly of scaffolds, identify misassembles, and discover
      thousands of SNPs for fine mapping. CONCLUSION: Exon capture sequencing and bulk
      segregant analysis is a rapid, inexpensive method to clone mutants identified in
      forward genetic screens. With sufficient meioses, this method can be generalized
      to any model system with a genome assembly, polished or unpolished, and in the
      latter case, it also provides many critical genomic resources.

PMID- 23171432
TI  - 1-Heteroaromatic-substituted tetraphenylboroles: pi-pi interactions between
      aromatic and antiaromatic rings through a B-C bond.
AB  - A series of 2,3,4,5-tetraphenylboroles substituted with different aromatic
      heterocycles (thiophene, furan, pyrrole, and dithiophene) in the 1-position were
      synthesized and characterized by means of NMR, elemental analysis, and X-ray
      crystallography. In contrast to known 2,3,4,5-tetraphenylboroles, X-ray
      diffraction revealed a nearly coplanar arrangement of the aromatic heterocycles
      and the antiaromatic borole scaffold as a result of pi-conjugation, which could
      be substantiated by DFT calculations. Furthermore, the 2,2'-dithiophene-bridged
      bisborole (14) exhibits a large bathochromic shift in the absorption spectrum,
      demonstrating the exceptional Lewis acidity of the nonannulated borolyl moiety.

PMID- 23171433
TI  - ALK-positive large B-cell lymphoma presenting with jejunal intussusception.

PMID- 23171435
TI  - Dried blood spots: analysis and applications.

PMID- 23171434
TI  - Nanoparticle permeation induces water penetration, ion transport, and lipid flip
      flop.
AB  - Nanoparticles are generally considered excellent candidates for targeted drug
      delivery. However, ion leakage and cytotoxicity induced by nanoparticle
      permeation is a potential problem in such drug delivery schemes because of the
      toxic effect of many ions. In this study, we have carried out a series of coarse
      grained molecular dynamics simulations to investigate the water penetration, ion
      transport, and lipid molecule flip-flop in a protein-free phospholipid bilayer
      membrane during nanoparticle permeation. The effect of ion concentration
      gradient, pressure differential across the membrane, nanoparticle size, and
      permeation velocity have been examined in this work. Some conclusions from our
      studies include (1) The number of water molecules in the interior of the membrane
      during the nanoparticle permeation increases with the nanoparticle size and the
      pressure differential across the membrane but is unaffected by the nanoparticle
      permeation velocity or the ion concentration gradient. (2) Ion transport is
      sensitive to the size of nanoparticle as well as the ion concentration gradient
      between two sides of the membrane; no anion/cation selectivity is observed for
      small nanoparticle permeation, while anions are preferentially translocated
      through the membrane when the size of nanoparticle is large enough. (3)
      Incidences of lipid molecule flip-flop increases with the size of nanoparticle
      and ion concentration gradient and decreases with the pressure differential and
      the nanoparticle permeation velocity.

PMID- 23171436
TI  - Dual effect of morphine in long-term social memory in rat.
AB  - BACKGROUND AND PURPOSE: Bimodal dose-response relationships have been
      demonstrated in animals and humans following morphine administration. We examined
      if systemic administration of morphine, in extremely low (MUg) and high (mg,
      analgesic) doses, changed the learning process. EXPERIMENTAL APPROACH: In the
      social learning test, an adult rat investigates a juvenile. The juvenile is
      submitted to a second encounter after a few days and investigation by the adult
      should be reduced. Morphine was administered before the first encounter between
      rats, and the critical test was performed 24, 72 or 168 h later, when animals
      were re-exposed to each other, in the absence of morphine. KEY RESULTS: Low doses
      of morphine, comparable with endogenous brain concentrations, enhanced long-term
      memory recognition; while high doses did the reverse, indicating the adult failed
      to recognize the juvenile. Recognition of a familiar rat appeared to be mediated
      within the brain accessory olfactory bulb (AOB) by an opioid system intrinsic to
      the olfactory system through MU-opioid receptors (MORs). At this supraspinal
      site, the PLC/PKC signalling pathway was activated by extremely low morphine
      doses. CONCLUSIONS AND IMPLICATIONS: Morphine treatment administration may either
      disrupt or facilitate social memory, depending on the dose, extending to memory
      formation the bimodal effects of morphine previously shown in pain. Social memory
      formation elicited by extremely low morphine doses, was mediated within the AOB
      by an opioid system, intrinsic to the olfactory system through MORs.

PMID- 23171437
TI  - Fc gamma receptor IIIa polymorphisms in advanced colorectal cancer patients
      correlated with response to anti-EGFR antibodies and clinical outcome.
AB  - BACKGROUND: Anti-EGFR monoclonal antibodies have shown efficacy in the treatment
      of metastatic colorectal cancer (mCRC). One of the mechanism is the antibody
      dependent cell-mediated cytotoxicity (ADCC) in which Fc region of the antibody
      binds to the Fc gamma receptors (FcgammaR) expressed by immune cells. The present
      study investigated the association between single nucleotide polymorphisms of
      FcgammaRIIa and FcgammaRIIIa and clinical outcome in mCRC treated with anti-EGFR
      antibodies. METHODS: Seventy-four consecutive patients with mCRC were analyzed.
      The genotypes for FcgammaRIIa-131 histidine (H)/arginine (R), FcgammaRIIIa-158
      valine (V)/phenylanaline (F) polymorphisms were evaluated by directly sequencing.
      Multiplex allele-specific polymerase chain reaction was performed for
      FcgammaRIIIa-158 valine (V)/phenylanaline (F). Correlations between FcgammaR
      polymorphisms, baseline patient and tumor features were studied by contingency
      tables and the chi-square test. The Kaplan-Meier product limit method was applied
      to the progression-free survival (PFS) curves. Univariate analysis was performed
      with the log-rank test. Cox proportional-hazards regression was used to analyze
      the effect of multiple risk factors on PFS. RESULTS: FcgammaRIIIa polymorphisms
      were significantly associated with response to anti-EGFR-based therapy in 49
      patients with kras wt tumors (p=0.035). There was not association with response
      for FcgammaRIIa polymorphisms. Furthermore, obtained results suggested that
      prognosis is particularly unfavorable for patients carrying the FcgammaRIIIa
      158F/F genotype (median PFS V/V, V/F, F/F: 18.2 vs 17.3 vs 9.4 months). No
      prognostic ability was identified for FcgammaRIIa polymorphisms. CONCLUSIONS: In
      mCRC patients the presence of FcgammaRIIIa-F can predict resistance to anti-EGFR
      therapy and unfavorable prognosis.

PMID- 23171439
TI  - A multiscale approximation in a heat shock response model of E. coli.
AB  - BACKGROUND: A heat shock response model of Escherichia coli developed by
      Srivastava, Peterson, and Bentley (2001) has multiscale nature due to its species
      numbers and reaction rate constants varying over wide ranges. Applying the method
      of separation of time-scales and model reduction for stochastic reaction networks
      extended by Kang and Kurtz (2012), we approximate the chemical network in the
      heat shock response model. RESULTS: Scaling the species numbers and the rate
      constants by powers of the scaling parameter, we embed the model into a one
      parameter family of models, each of which is a continuous-time Markov chain.
      Choosing an appropriate set of scaling exponents for the species numbers and for
      the rate constants satisfying balance conditions, the behavior of the full
      network in the time scales of interest is approximated by limiting models in
      three time scales. Due to the subset of species whose numbers are either
      approximated as constants or are averaged in terms of other species numbers, the
      limiting models are located on lower dimensional spaces than the full model and
      have a simpler structure than the full model does. CONCLUSIONS: The goal of this
      paper is to illustrate how to apply the multiscale approximation method to the
      biological model with significant complexity. We applied the method to the heat
      shock response model involving 9 species and 18 reactions and derived simplified
      models in three time scales which capture the dynamics of the full model.
      Convergence of the scaled species numbers to their limit is obtained and errors
      between the scaled species numbers and their limit are estimated using the
      central limit theorem.

PMID- 23171438
TI  - Replication kinetics of duck enteritis virus UL16 gene in vitro.
AB  - BACKGROUND: The function and kinetics of some herpsvirus UL16 gene have been
      reported. But there was no any report of duck enteritis virus (DEV) UL16 gene.
      FINDINGS: The kinetics of DEV UL16 gene was examined in DEV CHv infected duck
      embryo fibroblasts (DEFs) by establishment of real-time quantitative reverse
      transcription polymerase chain reaction assay (qRT-PCR) and western-blotting. In
      this study, UL16 mRNA was transcript at a low level from 0-18 h post-infection
      (p.i), and peaked at 36 h p.i. It can't be detected in the presence of acyclovir
      (ACV). Besides, western-blotting analysis showed that UL16 gene expressed as an
      apparent 40-KDa in DEV infected cell lysate from 12 h p.i, and rose to peak level
      at 48 h p.i consistent with the qRT-PCR result. CONCLUSIONS: These results
      provided the first evidence of the kinetics of DEV UL16 gene. DEV UL16 gene was a
      late gene and dependent on viral DNA synthesis.

PMID- 23171440
TI  - Validation of the Insomnia in the Elderly Scale for the detection of insomnia in
      older adults.
AB  - AIM: The main objective of this study was the validation of a brief support
      instrument for the diagnosis of insomnia in older adults. METHODS: An
      observational study was carried out for the evaluation of the Insomnia in the
      Elderly Scale using the psychiatric interview as the gold standard. Data was
      collected in a primary care setting in the city of Albacete, Spain. Participants
      were 926 non-institutionalized older adults aged >= 65 years. RESULTS: Sleep
      characteristics, and the health and sociodemographic status of the participants
      were assessed. The Insomnia in the Elderly Scale is divided into two subscales
      for the evaluation of the Diagnostic and Statistical Manual of Mental Disorders,
      Fouth Edition criteria A and B for insomnia. The area under the receiver
      operating characteristic curve for subscale A was 0.868. The cut-off point to
      detect the presence of diagnostic criterion A for insomnia was a score of >= 3
      (sensitivity: 86.4%; specificity: 69.5%). The area under the receiver operating
      characteristic curve for subscale B was 0.832. The cut-off point to detect the
      presence of diagnostic criterion B was a score of >= 2 (sensitivity: 86.3%;
      specificity: 66.4%). CONCLUSIONS: The Insomnia in the Elderly Scale has
      appropriate psychometric properties. This scale compensates for the lack of
      validated instruments for use in the population aged 65 years or older. The fact
      that it is divided into two subscales to separately evaluate the insomnia
      criteria enables us to detect the presence of each of them. Finally, it has been
      validated in participants aged 65 years and older, which is the target population
      for this scale.

PMID- 23171442
TI  - Severe hyperkalemia requiring hospitalization: predictors of mortality.
AB  - INTRODUCTION: Severe hyperkalemia, with potassium (K+) levels >= 6.5 mEq/L, is a
      potentially life-threatening electrolyte imbalance. For prompt and effective
      treatment, it is important to know its risk factors, clinical manifestations, and
      predictors of mortality. METHODS: An observational cohort study was performed at
      2 medical centers. A total of 923 consecutive Korean patients were analyzed. All
      were 19 years of age or older and were hospitalized with severe hyperkalemia
      between August 2007 and July 2010; the diagnosis of severe hyperkalemia was made
      either at the time of admission to the hospital or during the period of
      hospitalization. Demographic and baseline clinical characteristics at the time of
      hyperkalemia diagnosis were assessed, and clinical outcomes such as in-hospital
      mortality were reviewed, using the institutions' electronic medical record
      systems. RESULTS: Chronic kidney disease (CKD) was the most common underlying
      medical condition, and the most common precipitating factor of hyperkalemia was
      metabolic acidosis. Emergent admission was indicated in 68.6% of patients, 36.7%
      had electrocardiogram findings typical of hyperkalemia, 24.5% had multi-organ
      failure (MOF) at the time of hyperkalemia diagnosis, and 20.3% were diagnosed
      with severe hyperkalemia at the time of cardiac arrest. The in-hospital mortality
      rate was 30.7%; the rate was strongly correlated with the difference between
      serum K+ levels at admission and at their highest point, and with severe medical
      conditions such as malignancy, infection, and bleeding. Furthermore, a higher in
      hospital mortality rate was significantly associated with the presence of cardiac
      arrest and/or MOF at the time of diagnosis, emergent admission, and intensive
      care unit treatment during hospitalization. More importantly, acute kidney injury
      (AKI) in patients with normal baseline renal function was a strong predictor of
      mortality, compared with AKI superimposed on CKD. CONCLUSIONS: Severe
      hyperkalemia occurs in various medical conditions; the precipitating factors are
      similarly diverse. The mortality rate is especially high in patients with severe
      underlying disease, coexisting medical conditions, and those with normal baseline
      renal function.

PMID- 23171443
TI  - Genomic impact of eukaryotic transposable elements.
AB  - The third international conference on the genomic impact of eukaryotic
      transposable elements (TEs) was held 24 to 28 February 2012 at the Asilomar
      Conference Center, Pacific Grove, CA, USA. Sponsored in part by the National
      Institutes of Health grant 5 P41 LM006252, the goal of the conference was to
      bring together researchers from around the world who study the impact and
      mechanisms of TEs using multiple computational and experimental approaches. The
      meeting drew close to 170 attendees and included invited floor presentations on
      the biology of TEs and their genomic impact, as well as numerous talks
      contributed by young scientists. The workshop talks were devoted to computational
      analysis of TEs with additional time for discussion of unresolved issues. Also,
      there was ample opportunity for poster presentations and informal evening
      discussions. The success of the meeting reflects the important role of Repbase in
      comparative genomic studies, and emphasizes the need for close interactions
      between experimental and computational biologists in the years to come.

PMID- 23171441
TI  - In vitro antimicrobial activity on clinical microbial strains and antioxidant
      properties of Artemisia parviflora.
AB  - BACKGROUND: Artemisia parviflora leaf extracts were evaluated for potential
      antimicrobial and antioxidant properties. Antimicrobial susceptibility assay was
      performed against ten standard reference bacterial strains. Antioxidant activity
      was analyzed using the ferric thiocyanate and 2, 2-Diphenyl-1-Picrylhydrazyl
      (DPPH) assays. Radical scavenging activity and total phenolic content were
      compared. Phytochemical analyses were performed to identify the major bioactive
      constitution of the plant extract. RESULTS: Hexane, methanol and ethyl acetate
      extracts of A. parviflora leaves exhibited good activity against the
      microorganisms tested. The n-hexane extract of A. parviflora showed high
      inhibition of the growth of Pseudomonas aeruginosa, Escherichia coli and Shigella
      flexneri. Methanol extract showed strong radical scavenging and antioxidant
      activity, other extracts showed moderate antioxidant activity. The major
      derivatives present in the extracts are of terpenes, steroids, phenols,
      flavonoids, tannins and volatile oil. CONCLUSIONS: The results obtained with n
      hexane extract were particularly significant as it strongly inhibited the growth
      of P. aeruginosa, E. coli and S. flexneri. The major constituent of the n-hexane
      extract was identified as terpenes. Strong antioxidant activity could be observed
      with all the individual extracts. The antimicrobial and antioxidant property of
      the extracts were attributed to the secondary metabolites, terpenes and phenolic
      compounds present in A. parviflora and could be of considerable interest in the
      development of new drugs.

PMID- 23171444
TI  - IL-12 based gene therapy in veterinary medicine.
AB  - The use of large animals as an experimental model for novel treatment techniques
      has many advantages over the use of laboratory animals, so veterinary medicine is
      becoming an increasingly important translational bridge between preclinical
      studies and human medicine. The results of preclinical studies show that gene
      therapy with therapeutic gene encoding interleukin-12 (IL-12) displays pronounced
      antitumor effects in various tumor models. A number of different studies
      employing this therapeutic plasmid, delivered by either viral or non-viral
      methods, have also been undertaken in veterinary oncology. In cats, adenoviral
      delivery into soft tissue sarcomas has been employed. In horses, naked plasmid
      DNA has been delivered by direct intratumoral injection into nodules of
      metastatic melanoma. In dogs, various types of tumors have been treated with
      either local or systemic IL-12 electrogene therapy. The results of these studies
      show that IL-12 based gene therapy elicits a good antitumor effect on
      spontaneously occurring tumors in large animals, while being safe and well
      tolerated by the animals. Hopefully, such results will lead to further
      investigation of this therapy in veterinary medicine and successful translation
      into human clinical trials.

PMID- 23171445
TI  - Reactions to threatening health messages.
AB  - BACKGROUND: Threatening health messages that focus on severity are popular, but
      frequently have no effect or even a counterproductive effect on behavior change.
      This paradox (i.e. wide application despite low effectiveness) may be partly
      explained by the intuitive appeal of threatening communication: it may be hard to
      predict the defensive reactions occurring in response to fear appeals. We examine
      this hypothesis by using two studies by Brown and colleagues, which provide
      evidence that threatening health messages in the form of distressing imagery in
      anti-smoking and anti-alcohol campaigns cause defensive reactions. METHODS: We
      simulated both Brown et al. experiments, asking participants to estimate the
      reactions of the original study subjects to the threatening health information (n
      = 93). Afterwards, we presented the actual original study outcomes. One week
      later, we assessed whether this knowledge of the actual study outcomes helped
      participants to more successfully estimate the effectiveness of the threatening
      health information (n = 72). RESULTS: Results showed that participants were
      initially convinced of the effectiveness of threatening health messages and were
      unable to anticipate the defensive reactions that in fact occurred. Furthermore,
      these estimates did not improve after participants had been explained the
      dynamics of threatening communication as well as what the effects of the
      threatening communication had been in reality. CONCLUSIONS: These findings are
      consistent with the hypothesis that the effectiveness of threatening health
      messages is intuitively appealing. What is more, providing empirical evidence
      against the use of threatening health messages has very little effect on this
      intuitive appeal.

PMID- 23171446
TI  - Microwave-assisted extraction and determination of citrus red 2 dye in oranges
      and orange juice by liquid chromatography-tandem mass spectrometry.
AB  - A fast, simple, low cost, and high-throughput method has been developed for the
      determination of citrus red 2 dye in orange and orange juice samples. The
      procedure is based on microwave-assisted extraction followed by liquid
      chromatography-tandem mass spectrometry (LC-MS/MS) analysis. The method was
      optimized, and the analyte was efficiently extracted from the samples in 30 min
      using hexane/acetone (v/v, 3 : 1). The method was validated and showed good
      linearity and selectivity. The limits of quantification (LOQs) were 5 MUg/kg
      (sample size of 2 g) for both orange and orange juice samples. The average
      recoveries, measured at 3 concentration levels (5, 10, and 20 MUg/kg), were in
      the range 77.5% to 87.6% for the compound tested with relative standard
      deviations below 7.3%. The proposed method is rapid, accurate, and could be
      utilized for the routine analysis of citrus red 2 dye in orange and orange juice
      samples.

PMID- 23171447
TI  - Upstream therapy with statin and recurrence of atrial fibrillation after
      electrical cardioversion. Review of the literature and meta-analysis.
AB  - BACKGROUND: Atrial fibrillation (AF) is the most common sustained arrhythmia
      observed in clinical practice. Electrical cardioversion (EC) is commonly used to
      restore and maintain sinus rhythm but it is characterized by high rate of
      recurrences. Several trials analyzed the effects of statins to reduce the
      recurrences in AF with contradictory results. METHODS: We performed a meta
      analysis of the interventional trials with statins in patients with persistent AF
      to evaluate recurrences after EC. Only randomized controlled trials were included
      in the analysis. Data sources included: Medline, ISI Web of Science, SCOPUS and
      Cochrane database (up to June 2012). Data extraction was performed by three
      authors. Study-specific odds ratios (ORs) were combined using fixed-effects
      model. RESULTS: Six studies with 515 patients were included in the analysis.
      Statins used in the selected trials were: atorvastatin (at dosages ranging from
      10 to 80 mg/day), pravastatin (40 mg/day) and rosuvastatin (20 mg/day). AF
      recurrence after EC occurred in 108/258 (41.8%) of patients treated with statins
      and in 132/257 (51.3%) patients not on treatment with statins. Compared with
      control, recurrences were significantly reduced with statin treatment (O.R.:
      0.662; 95% C.I., 0.45-0.96; p=0.03); statin treatment was associated with an
      absolute risk reduction of 0.095 and a number needed to treat of 11. CONCLUSIONS:
      This review suggests that statin therapy was significantly associated with a
      decreased risk of recurrence in patients with persistent AF after EC.

PMID- 23171448
TI  - New challenges and frontiers in Experimental Dermatology  publishing: online
      only, Free Access, mini-blogs, 'Commentary from the Board', 'Hypotheses Letters'.

PMID- 23171449
TI  - Quantification of Demodex folliculorum by PCR in rosacea and its relationship to
      skin innate immune activation.
AB  - The aim of this study is to quantify D. folliculorum colonisation in rosacea
      subtypes and age-matched controls and to determine the relationship between D.
      folliculorum load, rosacea subtype and skin innate immune system activation
      markers. We set up a multicentre, cross-sectional, prospective study in which 98
      adults were included: 50 with facial rosacea, including 18 with
      erythematotelangiectatic rosacea (ETR), and 32 with papulopustular rosacea (PPR)
      and 48 age- and sex-matched healthy volunteers. Non-invasive facial samples were
      taken to quantify D. folliculorum infestation by quantitative PCR and evaluate
      inflammatory and immune markers. Analysis of the skin samples show that D.
      folliculorum was detected more frequently in rosacea patients than age-matched
      controls (96% vs 74%, P < 0.01). D. folliculorum density was 5.7 times higher in
      rosacea patients than in healthy volunteers. Skin sample analysis showed a higher
      expression of genes encoding pro-inflammatory cytokines (Il-8, Il-1b, TNF-a) and
      inflammasome-related genes (NALP-3 and CASP-1) in rosacea, especially PPR.
      Overexpression of LL-37 and VEGF, as well as CD45RO, MPO and CD163, was observed,
      indicating broad immune system activation in patients with rosacea. In
      conclusion, D. folliculorum density is highly increased in patients with rosacea,
      irrespective of rosacea subtype. There appears to be an inverse relationship
      between D. folliculorum density and inflammation markers in the skin of rosacea
      patients, with clear differences between rosacea subtypes.

PMID- 23171450
TI  - Intercellular pathway through hyaluronic acid in UVB-induced inflammation.
AB  - Ultraviolet B (UVB) radiation induces inflammation in the skin specifically at
      the site of exposure. We unexpectedly found that UVB-induced inflammation was not
      induced in gp91phox-depleted mice. To test whether gp91phox is directly involved
      in UVB-induced inflammation, neutrophil- and hyaluronic acid-depleted mice were
      also irradiated and examined for their response. Hyaluronic acid-depleted mice
      showed strongly inhibited UVB-induced inflammation, but the neutrophil-depleted
      mice did not exhibit any suppressed UVB-induced inflammation. To elucidate the
      pathway by which UVB irradiation induced inflammation, we examined the expression
      of nucleotide-binding domain, leucine-rich-containing family, pyrin domain
      containing-3 (NLRP3) and caspase-1 in the mouse skin. An increase in the
      expression of NLRP3 and caspase-1 was seen following the UVB irradiation of C57BL
      mice; however, the UVB-irradiated gp91phox-knockout (gp91phox(-/-)) mice did not
      have this increase in expression. Furthermore, the plasma IL-1beta level
      increased after the UVB irradiation in C57BL mice, but there was no change in the
      gp91phox(-/-) mice. These results clearly indicate that nicotinamide adenine
      dinucleotide phosphate oxidase is activated by gp91phox, which is expressed on
      the surface in response to the increased expression of hyaluronic acid induced by
      UVB irradiation, and as result, the generation of reactive oxygen species (ROS)
      increases. This ROS activate NLRP3, and NLRP3 leads to the production of caspase
      1, which subsequently increases IL-1beta, thereby finally inducing inflammation.
      It is thought that this system may play an important role in the damage and
      ageing of skin, and further studies are necessary to confirm these finding.

PMID- 23171451
TI  - CD1d-dependent, iNKT-cell cytotoxicity against keratinocytes in allergic contact
      dermatitis.
AB  - Conventional CD8+ T-lymphocytes are thought to be major effector cells in
      allergic contact dermatitis (ACD). However, previous work has demonstrated a
      significant population of invariant natural killer T-cells (iNKT-cells) in the
      elicitation phase of ACD. In this study, we investigate whether iNKT-cells have
      the capacity to serve as effector lymphocytes in ACD. Using in situ staining of
      skin biopsy specimens from ACD lesions, we observed intra-epidermal iNKT-cells.
      Presence of these cells provides the possibility of interactions with
      keratinocytes (KC), Langerhans cells (LC) and CD1d-bearing antigen-presenting
      cells (APC). Investigation into gene expression profiles of cytotoxic effector
      molecules in seven different cases of ACD found that the expression of perforin
      and granzymes A, B and K were significantly elevated in ACD relative to paired
      clinically normal skin. Immunostaining of ACD skin biopsy specimens revealed that
      these cytotoxic granules indeed localized to iNKT-cells. Studies of antigen
      presentation of KC to iNKT-cells show that these epithelial cells do not activate
      the expression of cytotoxicity effector genes in resting iNKT-cells, but had the
      capacity to serve as targets for activated iNKT-cells, which was dependent on
      CD1d expression. Mature LC were not able to present glycolipids to iNKT-cells and
      did not up-regulate CD1d in vitro to a variety of maturational stimuli or in vivo
      during ACD. These data suggest that iNKT-cells can serve as effector cells during
      human ACD and provide the rationale for developing inhibitory glycolipids as
      therapeutic agents for ACD.

PMID- 23171452
TI  - Electron spectroscopic analysis of the human lipid skin barrier: cold atmospheric
      plasma-induced changes in lipid composition.
AB  - The lipids of the stratum corneum comprise the most important components of the
      skin barrier. In patients with ichthyoses or atopic dermatitis, the composition
      of the skin barrier lipids is disturbed resulting in dry, scaly, itching
      erythematous skin. Using the latest X-Ray Photoelectron Spectroscopy (XPS)
      technology, we investigated the physiological skin lipid composition of human
      skin and the effects of cold atmospheric plasma treatment on the lipid
      composition. Skin lipids were stripped off forearms of six healthy volunteers
      using the cyanoacrylate glue technique, plasma treated or not and then subjected
      to detailed XPS analysis. We found that the human lipid skin barrier consisted of
      84.4% carbon (+1.3 SEM%), 10.8% oxygen (+1.0 SEM%) and 4.8% nitrogen (+0.3 SEM%).
      The composition of physiological skin lipids was not different in males and
      females. Plasma treatment resulted in significant changes in skin barrier lipid
      stoichiometry. The total carbon amount was reduced to 76.7%, and the oxygen
      amount increased to 16.5%. There was also a slight increase in nitrogen to 6.8%.
      These changes could be attributed to reduced C-C bonds and increased C-O, C=O, C
      N and N-C-O bonds. The moderate increase in nitrogen was caused by an increase in
      C-N and N-C-O bonds. Our results show for the first time that plasma treatment
      leads to considerable changes in the human skin lipid barrier. Our proof of
      principle investigations established the technical means to analyse, if plasma
      induced skin lipid barrier changes may be beneficial in the treatment of
      ichthyotic or eczematous skin.

PMID- 23171453
TI  - Blocking glutamate-mediated signalling inhibits human melanoma growth and
      migration.
AB  - Glutamate is an excitatory neurotransmitter that has been shown to regulate the
      proliferation, migration and survival of neuronal progenitors in the central
      nervous system through its action on metabotropic and ionotropic glutamate
      receptors (GluRs). Antagonists of ionotropic GluRs have been shown to cause a
      rapid and reversible change in melanocyte dendritic morphology, which is
      associated with the disorganization of actin and tubulin microfilaments in the
      cytoskeleton. Intracellular expression of microtubule-associated protein (MAP) 2a
      affects the assembly, stabilization and bundling of microtubules in melanoma
      cells; stimulates the development of dendrites; and suppresses melanoma cell
      migration and invasion. In this study, we investigated the relationship between
      glutamate-mediated signalling and microtubules, cell dendritic morphology and
      melanoma cell motility. We found that metabotropic GluR1 and N-methyl-d-aspartate
      receptor antagonists increased dendritic branching and inhibited the motility,
      migration and proliferation of melanoma cells. We also demonstrated that the
      invasion and motility of melanoma cells are significantly inhibited by the
      combination of increased expression of MAP2a and either metabotropic GluR1 or N
      methyl-d-aspartate receptor antagonists. Moreover, the blockade of glutamate
      receptors inhibited melanoma growth in vivo. Collectively, these results
      demonstrate the importance of glutamate signalling in human melanoma and suggest
      that the blockade of glutamate receptors is a promising novel therapy for
      treating melanoma.

PMID- 23171454
TI  - Genetic support for the role of the NLRP3 inflammasome in psoriasis
      susceptibility.
AB  - NACHT leucine-rich repeat- and PYD-containing (NLRP)3 protein controls the
      inflammasome by regulating caspase-1 activity and interleukin (IL)-1beta
      processing. The contribution of IL-1beta in the pathogenesis of psoriasis is well
      recognized. Polymorphisms in NLRP3 and caspase recruitment domain-containing
      protein (CARD)8, a negative regulator of caspase-1 activity, have been associated
      with susceptibility to common inflammatory diseases, such as Crohn's disease and
      rheumatoid arthritis. To investigate the role for genetic variants in the NLRP3
      inflammasome in psoriasis susceptibility. In a patient sample comprising 1988
      individuals from 491 families and 1002 healthy controls, genotypes for four
      selected single-nucleotide polymorphisms (SNPs) in NLRP3 (three SNPs) and CARD8
      (one SNP) were determined by TaqMan((r)) Allelic Discrimination. Using the
      transmission disequilibrium test (TDT), a significant increase in the
      transmission of the NLRP3 rs10733113G genotype to a subgroup of patients with
      more widespread psoriasis was demonstrated (P = 0.015). Using logistic regression
      analysis in 741 patients with psoriasis and 1002 controls, the CARD8 rs2043211
      genotype was significantly different in cases and controls in overall terms [OR
      1.3 (1.1-1.5), P = 0.004] and for both genders. Our data support the hypothesis
      that the inflammasome plays a role in psoriasis susceptibility.

PMID- 23171455
TI  - Penetration and biological effects of topically applied cyclosporin A
      nanoparticles in a human skin organ culture inflammatory model.
AB  - Systemic antipsoriatic therapies have potentially life-threatening, long-term
      side effects. The efficacy of topical drugs is poor, but may be improved by the
      use of delivery systems based on drug nanoparticles. To produce nanoparticles
      (NP) composed of cyclosporin A, a classical antipsoriatic drug, and to
      investigate their penetration and biological effects in human skin affected by
      psoriatic symptoms, poly-epsilon-caprolactone (PCL) and cyclosporin A (CsA) NP
      were prepared by the solvent evaporation method. Skin penetration was followed
      using fluorescently labeled NP in human skin organ cultures (hSOC). Psoriatic
      symptoms were mimicked in hSOC by the treatment with epidermal growth factor
      (EGF) and bacterial lipopolysaccharide (LPS). Cell viability in hSOC was
      evaluated by the resazurin test, and cytokine secretion into the growth medium
      was measured by immunodetection. We showed that topically applied NP diffused
      throughout the epidermis within two hours and through the dermis within the
      following day. They significantly reduced the secretion of inflammatory cytokines
      IL-1beta, IL-6, IL-8, IL-20 and IL-23. At active doses, no cytotoxicity was
      detected. This type of NP display relevant properties for the use as topical anti
      inflammatory agents and may help to resorb psoriatic lesions.

PMID- 23171456
TI  - Human melanoma cells in the rhombencephalon of the chick embryo: a novel model
      for brain metastasis.
AB  - Malignant melanoma has the highest propensity to metastasize to the brain of all
      primary neoplasms in adults. Here, we describe invasive growth and the
      development of melanoma metastases from suspensions of human melanoma cells in
      the brain of the chick embryo. Patient-derived melanoma cells and established
      melanoma cell lines were injected into the rhombencephalic brain vesicle of the
      two-day-chick embryo. After 48 and 96 h, tumor formation was studied in serial
      paraffin sections with melanoma-specific HMB45 and human-specific MIB1
      proliferation markers. The majority of the cells injected into the embryonic
      liquor cavity perished. Only melanoma cells in newly formed aggregates or when
      attached to the dorsal roof plate escaped apoptosis. Local invasion occurred not
      in the ventral differentiating neural epithelium but only in the roof plate.
      Although after 48 h melanoma cells invaded the rhombencephalic roof plate
      profusely at both sides, after 96 h typically one large tumor developed in the
      midline between roof plate and the dorsal surface epithelium. From the tumor,
      single cells invaded the mesenchyme and blood vessels. Cell lines with different
      invasive properties retained their graded invasive behaviour. Maximally invasive
      cells formed continuous tracks via vessels and along nerve fibres. The central
      tumor in the roof plate of the chick embryo rhombencephalon resembles a
      metastatic nodule in the patients with melanoma. Penetration of the roof plate
      epithelium, tumor formation and invasion of surrounding tissues by single cells
      can reliably be reproduced. The chick embryo model can be used for molecular
      studies of early phases of melanoma brain metastasis.

PMID- 23171457
TI  - Improved method of differentiation, selection and amplification of human
      melanocytes from the hair follicle cell pool.
AB  - Hair root harbours a complex cell pool with an immense developmental potential.
      Several lineages, including skin, can be differentiated from the multipotent to
      pluripotent cells of outer root sheath (ORS) of hair follicle. Outer root sheath
      presents the most opulent non-invasively gained adult stem cell source known. For
      the purposes of cultivating melanocytes designated for graft-based treatments of
      depigmentation disorders, we have established an ex vivo/in vitro cultivation
      method by introducing several methodological improvements to the ORS explant
      method of Dieckmann. As a result, we gained a higher, purer yield of
      differentiated melanocytes in half the time (at least 10(6) of 95% pure cells in
      4 weeks). This reliable cultivation procedure begins with the epilation of 60
      hairs and yields high numbers of ORS melanocytes that could be used for grafting
      applications. The procedure not only utilises the developmental potential of hair
      root cell pool and favors differentiation into melanocytes, but also contributes
      to the general trend of minimal-to-non-invasive strategies for regenerative
      medicine.

PMID- 23171458
TI  - A sprayable luminescent pH sensor and its use for wound imaging in vivo.
AB  - Non-invasive luminescence imaging is of great interest for studying biological
      parameters in wound healing, tumors and other biomedical fields. Recently, we
      developed the first method for 2D luminescence imaging of pH in vivo on humans,
      and a novel method for one-stop-shop visualization of oxygen and pH using the RGB
      read-out of digital cameras. Both methods make use of semitransparent sensor
      foils. Here, we describe a sprayable ratiometric luminescent pH sensor, which
      combines properties of both these methods. Additionally, a major advantage is
      that the sensor spray is applicable to very uneven tissue surfaces due to its
      consistency. A digital RGB image of the spray on tissue is taken. The signal of
      the pH indicator (fluorescein isothiocyanate) is stored in the green channel (G),
      while that of the reference dye [ruthenium(II)-tris-(4,7-diphenyl-1,10
      phenanthroline)] is stored in the red channel (R). Images are processed by
      rationing luminescence intensities (G/R) to result in pseudocolor pH maps of
      tissues, e.g. wounds.

PMID- 23171459
TI  - Extracellular histones inhibit hair shaft elongation in cultured human hair
      follicles and promote regression of hair follicles in mice.
AB  - Release of histone H4 in rat vibrissa dermal papilla (DP) cells exposed to sub
      toxic dose of colchicines has been recently reported. In addition, exposure to
      histone H4 has been reported to result in inhibited proliferation and reduced
      alkaline phosphatase (ALP) activity of cultured vibrissa DP cells. These findings
      prompted us to investigate the role of extracellular histones in hair growth
      using cultured human hair follicles and hair cycling using back skin of mice. We
      report here that exposure of cultured hair follicles to histone H4 and H2A
      resulted in significant inhibition of elongation of hair shafts, decreased
      expression of IGF-1 and decreased expression and activity of ALP. Injection of
      histones into hypodermis of mice during anagen resulted in premature onset of
      catagen. Findings of the current study provide strong evidence suggesting the
      inhibitory role of extracellular histones in hair growth.

PMID- 23171460
TI  - Suppression of UV-induced damage by a liposomal sunscreen: a prospective, open
      label study in patients with cutaneous lupus erythematosus and healthy controls.
AB  - This study aimed to determine whether a broad-spectrum liposomal sunscreen with a
      very high sun protection factor (Daylong actinica) can prevent damage induced by
      ultraviolet (UV) irradiation in patients with cutaneous lupus erythematosus (CLE)
      and healthy controls (HCs) under standardised conditions. In 20 patients with CLE
      and 10 HCs, defined areas of sunscreen-untreated and sunscreen-treated skin on
      the upper back were irradiated with combined UVA/UVB light. Disease-specific skin
      lesions were induced by UVA/UVB light in the untreated areas of nine patients
      with CLE; no specific eruptions or any sun damage was observed in the sunscreen
      treated areas in any of the CLE patients, nor in the HCs. Histological analysis
      of skin biopsy specimens confirmed the clinical results. In conclusion, the use
      of a high-protection, broad-spectrum sunscreen can prevent UV-induced damage in
      patients with CLE and HCs.

PMID- 23171461
TI  - Strong induction of AIM2 expression in human epidermis in acute and chronic
      inflammatory skin conditions.
AB  - Absent in melanoma 2 (AIM2) is a double-stranded DNA receptor, and its activation
      initiates an interleukin-1 beta processing inflammasome. AIM2 is implicated in
      host defense against several pathogens, but could hypothetically also contribute
      to autoinflammatory or autoimmune diseases, such as is the case for NLRP3. Using
      thoroughly characterised antibodies, we analysed AIM2 expression in human tissues
      and primary cells. A strong epidermal upregulation of AIM2 protein expression was
      observed in several acute and chronic inflammatory skin disorders, such as
      psoriasis, atopic dermatitis, venous ulcera, contact dermatitis, and experimental
      wounds. We also found AIM2 induction by interferon-gamma in submerged and three
      dimensional in vitro models of human epidermis. Our data highlight the dynamics
      of epidermal AIM2 expression, showing Langerhans cell and melanocyte-restricted
      expression in normal epidermis but a pronounced induction in subpopulations of
      epidermal keratinocytes under inflammatory conditions.

PMID- 23171462
TI  - The role of AHI1 and CDKN1C in cutaneous T-cell lymphoma progression.
AB  - Cutaneous T-cell lymphoma (CTCL) is the most common lymphoma of the skin. Recent
      reports suggest that AHI1 is overexpressed in a subset of CTCL-derived cell
      lines, where it downregulates the expression of CDKN1C tumor suppressor gene. In
      the current work, we test the expression of these genes in 60 patients with
      Mycosis Fungoides and Sezary Syndrome by RT-PCR and correlate our findings with 6
      years of clinical follow-up. These findings reveal that AHI1 and CDKN1C exhibit
      opposite expression patterns, where AHI1 is expressed in poor and intermediate
      prognosis patients, while CDKN1C is expressed in favourable prognosis patients.
      Kaplan-Meier analysis documents that downregulation of CDKN1C is associated with
      poor disease outcome in patients with CTCL, while upregulation of AHI1 shows a
      weak association with aggressive disease course.

PMID- 23171463
TI  - A novel missense mutation of the CYLD gene identified in a Hungarian family with
      Brooke-Spiegler syndrome.
AB  - Brooke-Spiegler syndrome (BSS; OMIM 605041) is an autosomal dominant disease
      characterized by skin appendage tumors due to mutations in the cylindromatosis
      gene (CYLD). We investigated a Hungarian BSS pedigree with two affected members,
      father and daughter. Direct sequencing demonstrated a novel missense mutation
      (c.2613C>G; p.His871Gln) in exon 19 within the ubiquitin-specific protease domain
      of the encoded protein. We performed preliminary analysis to reveal the
      functional role of this novel mutation. Our data suggest that this novel CYLD
      mutation leads to increased ubiquitination of NEMO through influencing
      deubiquitinating activity of the CYLD protein and thus may result in enhanced NF
      kappaB signalling.

PMID- 23171464
TI  - Attenuation of contact hypersensitivity by cell-permeable heat shock protein 70
      in BALB/c mouse model.
AB  - In contact hypersensitivity (CHS), multiple cells, inflammatory mediators and
      cytokines are known to be involved in the regulation of the immune response.
      Previously, we revealed the reactive oxygen species generation by 2, 4, 6
      trinitrobenzene sulphonic acid (TNBS) in vivo, followed by heat shock protein 70
      (Hsp70) carbonylation and the exogenous antioxidant role of cell-permeable Hsp70.
      Here, we demonstrate the role of Hsp70 using cell-permeable Hsp70 in the mouse
      CHS model. Pretreatment of cell-permeable Hsp70: (i) suppressed ear swelling;
      (ii) down-regulated phosphorylated p38, but up-regulated phosphorylated
      extracellular signal-regulated kinase; (iii) increased population of CD4(+)
      CD25(+) Foxp3(+)  T cells; (iv) decreased secretion of tumor necrosis factor
      alpha (TNF-alpha), IL-12, interferon-gamma and IL-2 and (v) but up-regulated IL-4
      and transforming growth factor beta (TGF-beta) in the lymph nodes. In conclusion,
      cell-permeable Hsp70 attenuates CHS through modulation of MAPK pathway and
      regulation of Th1, Th2 and regulatory T cells.

PMID- 23171465
TI  - Association between non-atopic hand eczema and interleukin-13 gene polymorphism
      in Taiwanese nursing population.
AB  - Chronic hand eczema is an important occupational skin disease with atopic
      dermatitis (AD) and wet work being the most important risk factors. This study
      was launched to analyse the potential association between AD-related inflammation
      genes and development of non-atopic hand eczema among nurses in University
      Hospital. Atopic eczema, non-atopic hand dermatitis and control groups were
      identified. The association between occurrence of non-atopic hand eczema and
      interleukin (IL)-13, IL-4 and IL-5 gene variants was analysed. IL13 rs20541 A
      allele [assuming recessive model; odds ratio (OR) = 3.38, 95% CI: (1.63-7.00)]
      showed association with development of non-atopic hand eczema. Additive score
      analyses showed combination of this gene variant with previously identified risk
      factors including certain SPINK5 polymorphism and more than 10 years of work
      experience conferred highest risk for development of non-atopic hand eczema. As
      non-atopic hand eczema made up significant portion of occupational skin diseases,
      further studies should be focused on this commonly encountered skin condition.

PMID- 23171466
TI  - Deletion of the Sox21 gene drastically affects hair lipids.
AB  - The effects of Sox21 gene deletion on hair lipids have been studied. For the
      cuticle-specific bound lipid 18-methyl eicosanoic acid (18-MEA), which was found
      to predominantly exist as the free form in Sox21(-/-)  hair, total levels and
      distribution were unexpectedly unchanged. This indicates that while the
      biosynthesis of 18-MEA is unaffected, its covalent attachment to the cuticle
      surface is disrupted by loss of keratin-associated protein binding partners.
      Although the class compositions differed, the total ceramide (CER) levels were
      found to be comparable between Sox21(+/+)  and Sox21(-/-)  hairs. Deletion of the
      gene was also found to increase cholesterol sulphate (CS) levels. The
      biosynthesis process might be associated with cuticle keratinocyte maturation,
      because both CS and CERs are known bioactives in keratinocyte differentiation.

PMID- 23171468
TI  - Well-defined iron catalyst for improved hydrogenation of carbon dioxide and
      bicarbonate.
AB  - The most efficient, stable, and easy-to-synthesize non-noble metal catalyst
      system for the reduction of CO(2) and bicarbonates is presented. In the presence
      of the iron(II)-fluoro-tris(2
      (diphenylphosphino)phenyl)phosphino]tetrafluoroborate complex 3, the
      hydrogenation of bicarbonates proceeds in good yields with high catalyst
      productivity and activity (TON > 7500, TOF > 750). High-pressure NMR studies of
      the hydrogenation of carbon dioxide demonstrate that the corresponding iron
      hydridodihydrogen complex 4 is crucial in the catalytic cycle.

PMID- 23171469
TI  - Laser-assisted pulpotomy in primary teeth: a systematic review.
AB  - OBJECTIVE: The purpose of this systematic review was to identify high-quality
      articles comparing laser with conventional pulpotomy procedures, and to assess
      whether laser treatment may offer an appreciable benefit over conventional
      approaches. METHODS: A systematic search was implemented for MEDLINE, WEB of
      SCIENCE and Cochrane's CENTRAL databases (1980-2012) to identify eligible
      studies. Two reviewers independently assessed the methodological quality of the
      articles (Kappa = 0.89) using specific study design-related quality assessment
      forms (Dutch Cochrane Collaboration). RESULTS: Seven articles met the inclusion
      criteria, of which five randomized control trials (RCT) and two case series (CS),
      involving Nd:YAG, Er:YAG, CO2 and 632/980 nm diode lasers. Although heterogeneity
      between pulpotomy studies was high, odds ratios (OR) were generally <1,
      indicating that laser is less successful than conventional pulpotomy techniques.
      CONCLUSION: Given the paucity and high heterogeneity of high-quality articles,
      general recommendations for the clinical use of laser in pulpotomy in primary
      teeth can yet not be formulated.

PMID- 23171470
TI  - Determination of trace elements in fluoropolymers after microwave-induced
      combustion.
AB  - An effective approach to the digestion of fluoropolymers for the determination of
      Ag, Ca, Cd, Co, Cr, Cu, Fe, K, Mg, Mn, and Ni impurities has been developed using
      microwave-induced combustion (MIC) in closed quartz vessels pressurized with
      oxygen. Samples that were examined included the following: polytetrafluorethylene
      (PTFE); polytetrafluoroethylene with an additional modifier,
      perfluoropropylvinylether (PTFE-TFM); and fluorinated ethylene propylene (FEP). A
      quartz device was used as a sample holder, and the influence of the absorber
      solution was evaluated. Determination of trace elements was performed by
      inductively coupled plasma-optical emission and mass spectrometry. Neutron
      activation analysis (NAA) was used for validation purposes. Results were also
      compared to those obtained using microwave-assisted acid extraction in high
      pressure closed systems. Dilute nitric acid (5 mol L(-1)), which was selected as
      the absorbing medium, was used to reflux the sample for 5 min after the
      combustion. Using these conditions, agreement for all analytes was better than
      98% when compared to values determined by NAA. The residual carbon content in the
      digests was lower than 1%, illustrating the high efficiency of the method. Up to
      8 samples could be digested within 30 min using MIC, providing a suitable
      throughput, taking into account the inertness of such samples.

PMID- 23171471
TI  - Enantioselective intermolecular [2 + 2 + 2] cycloadditions of ene-allenes with
      allenoates.
AB  - An enantioselective [2 + 2 + 2] cycloaddition of ene-allenes with allenoates is
      described, which transforms simple pi-components into stereochemically complex
      carbocycles in a single step. The rhodium(I)-catalyzed cycloaddition proceeds
      with good levels of enantioselectivity, and with high levels of regio-, chemo-,
      and diastereoselectivity. Our results are consistent with a mechanism involving
      an enantioselective intermolecular allene-allene oxidative coupling.

PMID- 23171472
TI  - Intraosseous samples can be used for opioid measurements--an experimental study
      in the anaesthetized pig.
AB  - AIM: The intraosseous route provides access to the systemic circulation in an
      emergency situation when other forms of vascular access are unavailable and there
      is an urgent need for fluid or drug therapy. The intraosseous access has also
      been used for collecting samples for laboratory testing. A question that may
      arise in an unconscious or severely exhausted patient is whether this condition
      is caused by an unknown drug. We aimed to evaluate whether intraosseous samples
      could be used to measure opioids and to study the accuracy and precision of such
      measurements. METHODS: Five healthy, anaesthetized pigs were treated with a
      continuous morphine infusion as part of the anaesthesia procedure. Samples for
      morphine testing were collected hourly for 6 h from two tibial intraosseous
      cannulae and a central venous catheter. RESULTS: The differences in morphine
      concentrations between the two tibial intraosseous cannulae were less than 10% in
      32/33 times. The values were also relatively stable over time. CONCLUSION: Our
      findings suggest that intraosseous samples can be used for the analysis of
      opioids if an IV route is not available.

PMID- 23171473
TI  - Adolescent bullying, cannabis use and emerging psychotic experiences: a
      longitudinal general population study.
AB  - BACKGROUND: Using longitudinal and prospective measures of psychotic experiences
      during adolescence, we assessed the risk of developing psychosis in three groups
      showing low, increasing and elevated psychotic experiences associated with
      bullying by peers and cannabis use in a UK sample of adolescents. Method Data
      were collected by self-report from 1098 adolescents (mean age 13.6 years; 60.9%
      boys) at five separate time points, equally separated by 6 months, across a 24
      month period. General growth mixture modelling identified three distinct
      trajectories of adolescents reporting psychotic experiences: elevated, increasing
      and low. RESULTS: Controlling for cannabis use, bullying by peers significantly
      predicted change in psychotic experiences between Time 2 and Time 5 in
      adolescents belonging to the increasing group. No effect was found for the
      elevated or low groups. Controlling for bullying, an earlier age of cannabis use
      and cannabis use more than twice significantly predicted change in psychotic
      experiences in adolescents belonging to the increasing group. Cannabis use at any
      age was significantly associated with subsequent change in psychotic experiences
      in the low group. Reverse causal associations were examined and there was no
      evidence for psychotic experiences at Time 1 predicting a subsequent change in
      cannabis use between Times 2 and 5 in any trajectory group. CONCLUSIONS: Bullying
      by peers and cannabis use are associated with adolescents' reports of increasing
      psychotic experiences over time. Further research into the longitudinal
      development of psychosis in adolescence and the associated risk factors would
      allow for early intervention programmes to be targeted more precisely.

PMID- 23171474
TI  - Iron deficiency causes a shift in AMP-activated protein kinase (AMPK) subunit
      composition in rat skeletal muscle.
AB  - BACKGROUND: As a cellular energy sensor, the 5'AMP-activated protein kinase
      (AMPK) is activated in response to energy stresses such as hypoxia and muscle
      contraction. To determine effects of iron deficiency on AMPK activation and
      signaling, as well as the AMPK subunit composition in skeletal muscle, rats were
      fed a control (C=50-58 mg/kg Fe) or iron deficient (ID=2-6 mg/kg Fe) diet for 6-8
      wks. RESULTS: Their respective hematocrits were 47.5% +/- 1.0 and 16.5% +/- 0.6.
      Iron deficiency resulted in 28.3% greater muscle fatigue (p<0.01) in response to
      10 min of stimulation (1 twitch/sec) and was associated with a greater reduction
      in phosphocreatine (C: Resting 24.1 +/- 0.9 MUmol/g, Stim 13.1 +/- 1.5 MUmol/g;
      ID: Resting 22.7 +/- 1.0 MUmol/g, Stim 3.2 +/- 0.7 MUmol/g; p<0.01) and ATP
      levels (C: Resting 5.89 +/- 0.48 MUmol/g, Stim 6.03 +/- 0.35 MUmol/g; ID: Resting
      5.51 +/- 0.20 MUmol/g, Stim 4.19 +/- 0.47 MUmol/g; p<0.05). AMPK activation
      increased with stimulation in muscles of C and ID animals. A reduction in
      Cytochrome c and other iron-dependent mitochondrial proteins was observed in ID
      animals (p<0.01). The AMPK catalytic subunit (alpha) was examined because both
      isoforms are known to play different roles in responding to energy challenges. In
      ID animals, AMPKalpha2 subunit protein content was reduced to 71.6% of C
      (p<0.05), however this did not result in a significant difference in resting
      AMPKalpha2 activity. AMPKalpha1 protein was unchanged, however an overall
      increase in AMPKalpha1 activity was observed (C: 0.91 pmol/mg/min; ID: 1.63
      pmol/mg/min; p<0.05). Resting phospho Acetyl CoA Carboxylase (pACC) was
      unchanged. In addition, we observed significant reductions in the beta2 and
      gamma3 subunits of AMPK in response to iron deficiency. CONCLUSIONS: This study
      indicates that chronic iron deficiency causes a shift in the expression of
      AMPKalpha, beta, and gamma subunit composition. Iron deficiency also causes
      chronic activation of AMPK as well as an increase in AMPKalpha1 activity in
      exercised skeletal muscle.

PMID- 23171475
TI  - Gene therapy for colorectal cancer by an oncolytic adenovirus that targets loss
      of the insulin-like growth factor 2 imprinting system.
AB  - BACKGROUND: Colorectal cancer is one of the most common malignant tumors
      worldwide. Loss of imprinting (LOI) of the insulin-like growth factor 2 (IGF2)
      gene is an epigenetic abnormality observed in human colorectal neoplasms. Our aim
      was to investigate the feasibility of using the IGF2 imprinting system for
      targeted gene therapy of colorectal cancer. RESULTS: We constructed a novel
      oncolytic adenovirus, Ad315-E1A, and a replication-deficient recombinant
      adenovirus, Ad315-EGFP, driven by the IGF2 imprinting system by inserting the H19
      promoter, CCCTC binding factor, enhancer, human adenovirus early region 1A (E1A)
      and enhanced green fluorescent protein (EGFP) reporter gene into a pDC-315
      shuttle plasmid. Cell lines with IGF2 LOI (HCT-8 and HT-29), which were infected
      with Ad315-EGFP, produced EGFP. However, no EGFP was produced in cell lines with
      maintenance of imprinting (HCT116 and GES-1). We found that Ad315-E1A
      significantly decreased cell viability and induced apoptosis only in LOI cell
      lines in vitro. In addition, mice bearing HCT-8-xenografted tumors, which
      received intratumoral administration of the oncolytic adenovirus, showed
      significantly reduced tumor growth and enhanced survival. CONCLUSIONS: Our
      recombinant oncolytic virus targeting the IGF2 LOI system inhibits LOI cell
      growth in vitro and in vivo, and provides a novel approach for targeted gene
      therapy.

PMID- 23171477
TI  - Effect of calcium source on structure and properties of sol-gel derived bioactive
      glasses.
AB  - The aim was to determine the most effective calcium precursor for synthesis of
      sol-gel hybrids and for improving homogeneity of sol-gel bioactive glasses. Sol
      gel derived bioactive calcium silicate glasses are one of the most promising
      materials for bone regeneration. Inorganic/organic hybrid materials, which are
      synthesized by incorporating a polymer into the sol-gel process, have also
      recently been produced to improve toughness. Calcium nitrate is conventionally
      used as the calcium source, but it has several disadvantages. Calcium nitrate
      causes inhomogeneity by forming calcium-rich regions, and it requires high
      temperature treatment (>400  degrees C) for calcium to be incorporated into the
      silicate network. Nitrates are also toxic and need to be burnt off. Calcium
      nitrate therefore cannot be used in the synthesis of hybrids as the highest
      temperature used in the process is typically 40-60  degrees C. Therefore, a
      different precursor is needed that can incorporate calcium into the silica
      network and enhance the homogeneity of the glasses at low (room) temperature. In
      this work, calcium methoxyethoxide (CME) was used to synthesize sol-gel bioactive
      glasses with a range of final processing temperatures from 60 to 800  degrees C.
      Comparison is made between the use of CME and calcium chloride and calcium
      nitrate. Using advanced probe techniques, the temperature at which Ca is
      incorporated into the network was identified for 70S30C (70 mol % SiO(2), 30 mol
      % CaO) for each of the calcium precursors. When CaCl(2) was used, the Ca did not
      seem to enter the network at any of the temperatures used. In contrast, Ca from
      CME entered the silica network at room temperature, as confirmed by X-ray
      diffraction, (29)Si magic angle spinning nuclear magnetic resonance spectroscopy,
      and dissolution studies. CME should be used in preference to calcium salts for
      hybrid synthesis and may improve homogeneity of sol-gel glasses.

PMID- 23171476
TI  - GraphAlignment: Bayesian pairwise alignment of biological networks.
AB  - BACKGROUND: With increased experimental availability and accuracy of bio
      molecular networks, tools for their comparative and evolutionary analysis are
      needed. A key component for such studies is the alignment of networks. RESULTS:
      We introduce the Bioconductor package GraphAlignment for pairwise alignment of
      bio-molecular networks. The alignment incorporates information both from network
      vertices and network edges and is based on an explicit evolutionary model,
      allowing inference of all scoring parameters directly from empirical data. We
      compare the performance of our algorithm to an alternative algorithm, Graemlin
      2.0.On simulated data, GraphAlignment outperforms Graemlin 2.0 in several
      benchmarks except for computational complexity. When there is little or no noise
      in the data, GraphAlignment is slower than Graemlin 2.0. It is faster than
      Graemlin 2.0 when processing noisy data containing spurious vertex associations.
      Its typical case complexity grows approximately as O(N2.6).On empirical bacterial
      protein-protein interaction networks (PIN) and gene co-expression networks,
      GraphAlignment outperforms Graemlin 2.0 with respect to coverage and specificity,
      albeit by a small margin. On large eukaryotic PIN, Graemlin 2.0 outperforms
      GraphAlignment. CONCLUSIONS: The GraphAlignment algorithm is robust to spurious
      vertex associations, correctly resolves paralogs, and shows very good performance
      in identification of homologous vertices defined by high vertex and/or
      interaction similarity. The simplicity and generality of GraphAlignment edge
      scoring makes the algorithm an appropriate choice for global alignment of
      networks.

PMID- 23171478
TI  - MRSA variant in companion animals.
AB  - Methicillin-resistant Staphylocoocus aureus (MRSA) harboring mecA(LGA251) has
      been isolated from humans and ruminants. Database screening identified this MRSA
      variant in cats, dogs, and a guinea pig in Germany during 2008-2011. The novel
      MRSA variant is not restricted to ruminants or humans, and contact with companion
      animals might pose a zoonotic risk.

PMID- 23171479
TI  - Identification of novel genes for bitter taste receptors in sheep (Ovis aries).
AB  - Genetic studies on taste sensitivity, and bitter taste receptors (T2R) in
      particular, are an essential tool to understand ingestive behavior and its
      relation to variations of nutritional status occurring in ruminants. In the
      present study, we conducted a data-mining search to identify T2R candidates in
      sheep by comparison with the described T2R in cattle and using recently available
      ovine genome. In sheep, we identified eight orthologs of cattle genes: T2R16,
      T2R10B, T2R12, T2R3, T2R4, T2R67, T2R13 and T2R5. The in silico predicted genes
      were then confirmed by PCR and DNA sequencing. The sequencing results showed a
      99% to 100% similarity with the in silico predicted sequence. Moreover, we
      address the chromosomal distribution and compare, in homology and phylogenetic
      terms, the obtained genes with the known T2R in human, mouse, dog, cattle, horse
      and pig. The eight novel genes identified map either to ovine chromosome 3 or 4.
      The phylogenetic data suggest a clustering by receptor type rather than by
      species for some of the receptors. From the species analyzed, we observed a clear
      proximity between the two ruminant species, sheep and cattle, in contrast with
      lower similarities obtained for the comparison of sheep with other mammals.
      Although further studies are needed to identify the complete T2R repertoire in
      domestic sheep, our data represent a first step for genetic studies on this
      field.

PMID- 23171480
TI  - Autochthonous gnathostomiasis, Brazil.

PMID- 23171481
TI  - Focused assessment with sonography for HIV-associated tuberculosis (FASH): a
      short protocol and a pictorial review.
AB  - BACKGROUND: Ultrasound can rapidly identify abnormal signs, which in high
      prevalence settings, are highly suggestive of extra-pulmonary tuberculosis
      (EPTB). Unfortunately experienced sonographers are often scarce in these
      settings. METHODS: A protocol for focused assessment with sonography for HIV
      associated tuberculosis (FASH) which can be used by physicians who are relatively
      inexperienced in ultrasound was developed. RESULTS: The technique as well as
      normal and pathological findings are described and the diagnostic and possible
      therapeutic reasoning explained. The protocol is intended for settings where the
      prevalence of HIV/TB co-infected patients is high. CONCLUSION: FASH is suitable
      for more rapid identification of EPTB even at the peripheral hospital level where
      other imaging modalities are scarce and most of the HIV and TB care will be
      delivered in the future.

PMID- 23171482
TI  - Prothrombotic gene variants as risk factors of acute myocardial infarction in
      young women.
AB  - BACKGROUND: Acute myocardial infarction (AMI) in young women represent an extreme
      phenotype associated with a higher mortality compared with similarly aged men.
      Prothrombotic gene variants could play a role as risk factors for AMI at young
      age. METHODS: We studied Factor V Leiden, FII G20210A, MTHFR C677T and beta
      fibrinogen -455G>A variants by real-time PCR in 955 young AMI (362 females) and
      in 698 AMI (245 females) patients. The data were compared to those obtained in
      909 unrelated subjects (458 females) from the general population of the same
      geographical area (southern Italy). RESULTS: In young AMI females, the allelic
      frequency of either FV Leiden and of FII G20210A was significantly higher versus
      the general population (O.R.: 3.67 for FV Leiden and O.R.: 3.84 for FII G20210A;
      p<0.001). Among AMI patients we showed only in males that the allelic frequency
      of the MTHFR C677T variant was significantly higher as compared to the general
      population. Such difference was due to a significantly higher frequency in AMI
      males of the MTHFR C677T variant homozygous genotype (O.R. 3.05). DISCUSSION AND
      CONCLUSION: Our data confirm that young AMI in females is a peculiar phenotype
      with specific risk factors as the increased plasma procoagulant activity of FV
      and FII. On the contrary, the homozygous state for the 677T MTHFR variant may
      cause increased levels of homocysteine and/or an altered folate status and thus
      an increased risk for AMI, particularly in males. The knowledge of such risk
      factors (that may be easily identified by molecular analysis) may help to improve
      prevention strategies for acute coronary diseases in specific risk-group
      subjects.

PMID- 23171484
TI  - The Child Health Research Centers: twenty-one years of promoting the development
      of pediatrician scientists from 1990-2011.

PMID- 23171483
TI  - Practice effects in a longitudinal, multi-center Alzheimer's disease prevention
      clinical trial.
AB  - BACKGROUND: Practice effects are a known threat to reliability and validity in
      clinical trials. Few studies have investigated the potential influence of
      practice on repeated screening measures in longitudinal clinical trials with a
      focus on dementia prevention. The current study investigates whether practice
      effects exist on a screening measure commonly used in aging research, the Memory
      Impairment Screen (MIS). METHODS: The PREADViSE trial is a clinical intervention
      study evaluating the efficacy of vitamin E and selenium for Alzheimer's disease
      prevention. Participants are screened annually for incident dementia with the
      MIS. Participants with baseline and three consecutive follow-ups who made less
      than a perfect score at one or more assessments were included in the current
      analyses (N=1,803). An additional subset of participants with four consecutive
      assessments but who received the same version of the MIS at baseline and first
      follow-up (N=301) was also assessed to determine the effects of alternate forms
      on mitigating practice. We hypothesized that despite efforts to mitigate practice
      effects with alternate versions, MIS scores would improve with repeated
      screening. Linear mixed models were used to estimate mean MIS scores over time.
      RESULTS: Among men with four visits and alternating MIS versions, although there
      is little evidence of a significant practice effect at the first follow-up, mean
      scores clearly improve at the second and third follow-ups for all but the oldest
      participants. Unlike those who received alternate versions, men given the same
      version at first follow-up show significant practice effects. CONCLUSION: While
      increases in the overall means were small, they represent a significant number of
      men whose scores improved with repeated testing. Such improvements could bias
      case ascertainment if not taken into account.

PMID- 23171485
TI  - 50 years ago in The Journal of Pediatrics: Observations on the etiology of acute
      bronchiolitis in infants.

PMID- 23171486
TI  - 50 years ago in The Journal of Pediatrics: Sensory neuropathy in a child.

PMID- 23171487
TI  - 50 years ago in The Journal of Pediatrics: cardiac failure and patency of the
      ductus arterious in early infancy.

PMID- 23171496
TI  - Non-communicable diseases in Mozambique: risk factors, burden, response and
      outcomes to date.
AB  - Mozambique is located on the East Coast of Africa bordering South Africa,
      Zimbabwe, Zambia, Malawi and Tanzania and is one of the poorest countries in the
      world. Currently NCDs account for 28% of deaths in Mozambique. Risk factors such
      as tobacco and alcohol use and poor diet are present in both urban and rural
      settings. Diseases such as hypertension and diabetes affect large proportions of
      the population, but people are often unaware of their condition or poorly
      managed. Data from studies on diabetes highlight the financial burden for NCD
      management in Mozambique for both the individual and health system. The National
      Strategic Plan for the prevention and control of NCDs in Mozambique has as its
      aim to create a positive environment to minimise or eliminate the exposure to
      risk factors and guarantee access to care. The plan has as its overall objective
      to reduce exposure to risk factors and morbidity and mortality due to NCDs and
      has 4 areas of intervention: 1) Prevention and health education with regards to
      NCDs; 2) Access to quality care, treatment and follow-up; 3) Prevention of
      disability and premature mortality and 4) Surveillance, research, monitoring and
      evaluation and advocacy for NCDs. The Ministry of Health developed projects for
      diabetes and hypertension and used these as key lessons that could then be
      applied to other NCDs. Mozambique, through political commitment from the Ministry
      of Health and the dedication of local champions, has been able to garner
      international support to improve care for people with diabetes and then use this
      to develop its National Plan for NCDs. Despite this increase in attention
      resources available do not match the challenge of NCDs in Mozambique.
      Mozambique's experience provides a practical example of actions that can be
      undertaken in a resource poor country to tackle the emerging burden of NCDs.

PMID- 23171497
TI  - Characteristics of the Colombian armed conflict and the mental health of
      civilians living in active conflict zones.
AB  - BACKGROUND: Despite the fact that the Colombian armed conflict has continued for
      almost five decades there is still very little information on how it affects the
      mental health of civilians. Although it is well established in post-conflict
      populations that experience of organised violence has a negative impact on mental
      health, little research has been done on those living in active conflict zones.
      Medecins Sans Frontieres provides mental health services in areas of active
      conflict in Colombia and using data from these services we aimed to establish
      which characteristics of the conflict are most associated with specific symptoms
      of mental ill health. METHODS: An analysis of clinical data from patients (N =
      6,353), 16 years and over, from 2010-2011, who consulted in the Colombian
      departments (equivalent to states) of Narino, Cauca, Putumayo and Caqueta. Risk
      factors were grouped using a hierarchical cluster analysis and the clusters were
      included with demographic information as predictors in logistic regressions to
      discern which risk factor clusters best predicted specific symptoms. RESULTS:
      Three clear risk factor clusters emerged which were interpreted as 'direct
      conflict related violence', 'personal violence not directly conflict-related' and
      'general hardship'. The regression analyses indicated that conflict related
      violence was more highly related to anxiety-related psychopathology than other
      risk factor groupings while non-conflict violence was more related to aggression
      and substance abuse, which was more common in males. Depression and suicide risk
      were represented equally across risk factor clusters. CONCLUSIONS: As the largest
      study of its kind in Colombia it demonstrates a clear impact of the conflict on
      mental health. Among those who consulted with mental health professionals,
      specific conflict characteristics could predict symptom profiles. However, some
      of the highest risk outcomes, like depression, suicide risk and aggression, were
      more related to factors indirectly related to the conflict. This suggests a need
      to focus on the systemic affects of armed conflict and not solely on direct
      exposure to fighting.

PMID- 23171499
TI  - Meta-analysis of clinical trial safety data in a drug development program:
      answers to frequently asked questions.
AB  - BACKGROUND: Meta-analyses of clinical trial safety data have risen in importance
      beyond regulatory submissions. During drug development, sponsors need to
      recognize safety signals early and adjust the development program accordingly, so
      as to facilitate the assessment of causality. Once a product is marketed,
      sponsors add postapproval clinical trial data to the body of information to help
      understand existing safety concerns or those that arise from other postapproval
      data sources, such as spontaneous reports. PURPOSE: This article focuses on
      common questions encountered when designing and performing a meta-analysis of
      clinical trial safety data. Although far from an exhaustive set of questions,
      they touch on some basic and often misunderstood features of conducting such meta
      analyses. METHODS: The authors reviewed the current literature and used their
      combined experience with regulatory and other uses of meta-analysis to answer
      common questions that arise when performing meta-analyses of safety data.
      RESULTS: We addressed the following topics: choice of studies to pool, effects of
      the method of ascertainment, use of patient-level data compared to trial-level
      data, the need (or not) for multiplicity adjustments, heterogeneity of effects
      and sources of it, and choice of fixed effects versus random effects.
      LIMITATIONS: The list of topics is not exhaustive and the opinions offered
      represent only our perspective; we recognize that there may be other valid
      perspectives. CONCLUSIONS: Meta-analysis can be a valuable tool for evaluating
      safety questions, but a number of methodological choices need to be made in
      designing and conducting any meta-analysis. This article provides advice on some
      of the more commonly encountered choices.

PMID- 23171498
TI  - Thought disorder in the meta-structure of psychopathology.
AB  - BACKGROUND: Dimensional models of co-morbidity have the potential to improve the
      conceptualization of mental disorders in research and clinical work, yet little
      is known about how relatively uncommon disorders may fit with more common
      disorders. The present study estimated the meta-structure of psychopathology in
      the US general population focusing on the placement of five under-studied
      disorders sharing features of thought disorder: paranoid, schizoid, avoidant and
      schizotypal personality disorders, and manic episodes as well as bipolar
      disorder. METHOD: Data were drawn from the National Epidemiologic Survey on
      Alcohol and Related Conditions, a face-to-face interview of 34 653 non
      institutionalized adults in the US general population. The meta-structure of 16
      DSM-IV Axis I and Axis II psychiatric disorders, as assessed by the Alcohol Use
      Disorder and Associated Disabilities Interview Schedule DSM-IV version (AUDADIS
      IV), was examined using exploratory and confirmatory factor analysis. RESULTS: We
      document an empirically derived thought disorder factor that is a subdomain of
      the internalizing dimension, characterized by schizoid, paranoid, schizotypal and
      avoidant personality disorders as well as manic episodes. Manic episodes exhibit
      notable associations with both the distress subdomain of the internalizing
      dimension as well as the thought disorder subdomain. The structure was replicated
      for bipolar disorder (I or II) in place of manic episodes. CONCLUSIONS: As our
      understanding of psychopathological meta-structure expands, incorporation of
      disorders characterized by detachment and psychoticism grows increasingly
      important. Disorders characterized by detachment and psychoticism may be well
      conceptualized, organized and measured as a subdimension of the internalizing
      spectrum of disorders. Manic episodes and bipolar disorder exhibit substantial co
      morbidity across both distress and thought disorder domains of the internalizing
      dimension. Clinically, these results underscore the potential utility of
      conceptualizing patient treatment needs using an approach targeting
      psychopathological systems underlying meta-structural classification rubrics.

PMID- 23171500
TI  - Review: some evidence of benefit for psychotherapies in borderline personality
      disorder.

PMID- 23171501
TI  - Suitability of cross-bred cows for organic farms based on cross-breeding effects
      on production and functional traits.
AB  - Data from 113 Dutch organic farms were analysed to determine the effect of cross
      breeding on production and functional traits. In total, data on 33 788 lactations
      between January 2003 and February 2009 from 15 015 cows were available. Holstein
      Friesian pure-bred cows produced most kg of milk in 305 days, but with the lowest
      percentages of fat and protein of all pure-bred cows in the data set. Cross
      breeding Holstein dairy cows with other breeds (Brown Swiss, Dutch Friesian,
      Groningen White Headed, Jersey, Meuse Rhine Yssel, Montbeliarde or Fleckvieh)
      decreased milk production, but improved fertility and udder health in most cross
      bred animals. In most breeds, heterosis had a significant effect (P < 0.05) on
      milk (kg in 305 days), fat and protein-corrected milk production (kg in 305 days)
      and calving interval (CI) in the favourable direction (i.e. more milk, shorter
      CI), but unfavourably for somatic cell count (higher cell count). Recombination
      was unfavourable for the milk production traits, but favourable for the
      functional traits (fertility and udder health). Farm characteristics, like soil
      type or housing system, affected the regression coefficients on breed components
      significantly. The effect of the Holstein breed on milk yield was twice as large
      in cubicle housing as in other housing systems. Jerseys had a negative effect on
      fertility only on farms on sandy soils. Hence, breed effects differ across
      farming systems in the organic farming and farmers can use such information to
      dovetail their farming system with the type of cow they use.

PMID- 23171503
TI  - Assessment of a spectral domain OCT segmentation software in a retrospective
      cohort study of exudative AMD patients.
AB  - BACKGROUND: To assess the ability of the Spectralis optical coherence tomography
      (OCT) segmentation software to identify the inner limiting membrane and Bruch's
      membrane in exudative age-related macular degeneration (AMD) patients. METHODS:
      Thirty-eight eyes of 38 naive exudative AMD patients were retrospectively
      included. They all had a complete ophthalmologic examination including Spectralis
      OCT at baseline, at month 1 and 2. Reliability of the segmentation software was
      assessed by 2 ophthalmologists. Reliability of the segmentation software was
      defined as good if both inner limiting membrane and Bruch's membrane were
      correctly drawn. RESULTS: A total of 38 patients charts were reviewed (114
      scans). The inner limiting membrane was correctly drawn by the segmentation
      software in 114/114 spectral domain OCT scans (100%). Conversely, Bruch's
      membrane was correctly drawn in 59/114 scans (51.8%). The software was less
      reliable in locating Bruch's membrane in case of pigment epithelium detachment
      (PED) than without PED (42.5 vs. 73.5%, respectively; p = 0.049), but its
      reliability was not associated with SRF or CME (p = 0.55 and p = 0.10,
      respectively). CONCLUSION: Segmentation of the inner limiting membrane was
      constantly trustworthy but Bruch's membrane segmentation was poorly reliable
      using the automatic Spectralis segmentation software. Based on this software,
      evaluation of retinal thickness may be incorrect, particularly in case of PED.
      PED is effectively an important parameter which is not included when measuring
      retinal thickness.

PMID- 23171502
TI  - Differential susceptibility of inbred mouse strains to chlorine-induced airway
      fibrosis.
AB  - Chlorine is a reactive gas that is considered a chemical threat agent. Humans who
      develop acute lung injury from chlorine inhalation typically recover normal lung
      function; however, a subset can experience chronic airway disease. To examine
      pathological changes following chlorine-induced lung injury, mice were exposed to
      a single high dose of chlorine, and repair of the lung was analyzed at multiple
      times after exposure. In FVB/NJ mice, chlorine inhalation caused pronounced
      fibrosis of larger airways that developed by day 7 after exposure and was
      associated with airway hyperreactivity. In contrast, A/J mice had little or no
      airway fibrosis and had normal lung function at day 7. Unexposed FVB/NJ mice had
      less keratin 5 staining (basal cell marker) than A/J mice in large intrapulmonary
      airways where epithelial repair was poor and fibrosis developed after chlorine
      exposure. FVB/NJ mice had large areas devoid of epithelium on day 1 after
      exposure leading to fibroproliferative lesions on days 4 and 7. A/J mice had
      airways covered by squamous keratin 5-stained cells on day 1 that transitioned to
      a highly proliferative reparative epithelium by day 4 followed by the
      reappearance of ciliated and Clara cells by day 7. The data suggest that lack of
      basal cells in the large intrapulmonary airways and failure to effect epithelial
      repair at these sites are factors contributing to the development of airway
      fibrosis in FVB/NJ mice. The observed differences in susceptibility to chlorine
      induced airway disease provide a model in which mechanisms and treatment of
      airway fibrosis can be investigated.

PMID- 23171504
TI  - Uremia suppresses immune signal-induced CYP27B1 expression in human monocytes.
AB  - BACKGROUND: Local production of 1,25-dihydroxyvitamin D (1,25(OH)(2)D) regulated
      by the CYP27B1 enzyme in monocytes contributes to the immunomodulatory effects of
      vitamin D. Uremia suppresses renal CYP27B1, but its impact on monocytic CYP27B1
      is incompletely understood. The present study aimed to elucidate this issue and
      to define the pathogenic role of p-cresyl sulfate (PCS), indoxyl sulfate (IndS),
      and fibroblast growth factor 23 (FGF23). METHODS: Resting or immune (interferon
      gamma + lipopolysaccharide)-stimulated THP1 cells and monocytes, isolated from
      healthy donors, were cultured in the presence of either healthy serum, uremic
      serum, PCS, IndS or FGF23. RNA expression levels for CYP27B1 and cytokines were
      quantified by RT-PCR and enzymatic CYP27B1 activity was measured 24 h after
      incubation. RESULTS: Culturing THP1 cells or human monocytes in the presence of
      uremic serum led to higher inflammatory cytokine and CYP27B1 expression. Immune
      signal-induced CYP27B1 expression and activity, conversely, was impaired in the
      presence of uremic serum. Similar effects were observed in the presence of FGF23,
      although significance was reached in immune-stimulated cells only. PCS and IndS
      failed to show any effect. CONCLUSIONS: Monocytic baseline CYP27B1 expression is
      increased in uremia, probably reflecting the microinflammatory state. Immune
      signal-induced CYP27B1 expression, conversely, is impaired in uremic conditions.
      Elevated FGF23 levels, but not PCS and IndS, may account, at least partly, for
      the dysregulation of monocytic CYP27B1 in uremia and, as such, may contribute to
      the high cardiovascular and infectious burden in chronic kidney disease.

PMID- 23171506
TI  - Mammography results in substantial overdiagnosis of breast cancer, concludes
      study.

PMID- 23171505
TI  - Self-referential and social cognition in a case of autism and agenesis of the
      corpus callosum.
AB  - BACKGROUND: While models of autism spectrum conditions (ASC) are emerging at the
      genetic level of analysis, clear models at higher levels of analysis, such as
      neuroanatomy, are lacking. Here we examine agenesis of the corpus callosum (AgCC)
      as a model at the level of neuroanatomy that may be relevant for understanding
      self-referential and social-cognitive difficulties in ASC. METHODS: We examined
      performance on a wide array of tests in self-referential and social-cognitive
      domains in a patient with both AgCC and a diagnosis of ASC. Tests included a
      depth-of-processing memory paradigm with self-referential and social-cognitive
      manipulations, self-report measures of self-consciousness, alexithymia, and
      empathy, as well as performance measures of first-person pronoun usage and
      mentalizing ability. The performance of the AgCC patient was compared to a group
      of individuals with ASC but without AgCC and with neurotypical controls. These
      comparison groups come from a prior study where group differences were apparent
      across many measures. We used bootstrapping to assess whether the AgCC patient
      exhibited scores that were within or outside the 95% bias-corrected and
      accelerated bootstrap confidence intervals observed in both comparison groups.
      RESULTS: Within the depth-of-processing memory paradigm, the AgCC patient showed
      decreased memory sensitivity that was more extreme than both comparison groups
      across all conditions. The patient's most pronounced difficulty on this task
      emerged in the social-cognitive domain related to information-processing about
      other people. The patient was similar to the ASC group in benefiting less from
      self-referential processing compared to the control group. Across a variety of
      other self-referential (i.e. alexithymia, private self-consciousness) and social
      cognitive measures (i.e. self-reported imaginative and perspective-taking
      subscales of empathy, mentalizing), the AgCC patient also showed more extreme
      scores than those observed for both of the comparison groups. However, the AgCC
      patient scored within the range observed in the comparison groups on measures of
      first-person pronoun usage and self-reported affective empathy subscales.
      CONCLUSIONS: We conclude that AgCC co-occurring with a diagnosis of ASC may be a
      relevant model at the level of neuroanatomy for understanding mechanisms involved
      in self-referential and high-level social-cognitive difficulties in ASC.

PMID- 23171507
TI  - Drug treatment reduces criminal behaviour in adults with ADHD by about a third,
      study shows.

PMID- 23171508
TI  - Safety profile and pharmacokinetic analyses of the anti-CTLA4 antibody
      tremelimumab administered as a one hour infusion.
AB  - BACKGROUND: CTLA4 blocking monoclonal antibodies provide a low frequency but
      durable tumor responses in patients with metastatic melanoma, which led to the
      regulatory approval of ipilimumab based on two randomized clinical trials with
      overall survival advantage. The similarly fully human anti-CTLA4 antibody
      tremelimumab had been developed in the clinic at a fixed rate infusion, resulting
      in very prolonged infusion times. A new formulation of tremelimumab allowed
      testing a shorter infusion time. METHODS: A phase 1 multi-center study to
      establish the safety and tolerability of administering tremelimumab as a 1-hour
      infusion to patients with metastatic melanoma. Secondary endpoints included
      pharmacokinetic and clinical effects of tremelimumab. RESULTS: No grade 3 or
      greater infusion-related adverse events or other adverse events preventing the
      administration of the full tremelimumab dose were noted in 44 treated patients.
      The overall side effect profile was consistent with prior experiences with anti
      CTLA4 antibodies. Objective tumor responses were noted in 11% of evaluable
      patients with metastatic melanoma, which is also consistent with the prior
      experience with CTLA4 antagonistic antibodies. CONCLUSIONS: This study did not
      identify any safety concerns when tremelimumab was administered as a 1-hour
      infusion. These data support further clinical testing of the 1-hour infusion of
      tremelimumab. (Clinical trial registration number NCT00585000).

PMID- 23171509
TI  - A compact frequency-domain photon migration system for integration into
      commercial hybrid small animal imaging scanners for fluorescence tomography.
AB  - The work presented herein describes the system design and performance evaluation
      of a miniaturized near-infrared fluorescence (NIRF) frequency-domain photon
      migration (FDPM) system with non-contact excitation and homodyne detection
      capability for small animal fluorescence tomography. The FDPM system was
      developed specifically for incorporation into a Siemens micro positron emission
      tomography/computed tomography (microPET/CT) commercial scanner for hybrid small
      animal imaging, but could be adapted to other systems. Operating at 100 MHz, the
      system noise was minimized and the associated amplitude and phase errors were
      characterized to be +/-0.7% and +/-0.3 degrees , respectively. To demonstrate the
      tomographic ability, a commercial mouse-shaped phantom with 50 uM IRDye800CW and
      68Ga containing inclusion was used to associate PET and NIRF tomography. Three
      dimensional mesh generation and anatomical referencing was accomplished through
      CT. A third-order simplified spherical harmonics approximation (SP3) algorithm,
      for efficient prediction of light propagation in small animals, was tailored to
      incorporate the FDPM approach. Finally, the PET-NIRF target co-localization
      accuracy was analyzed in vivo with a dual-labeled imaging agent targeting
      orthotopic growth of human prostate cancer. The obtained results validate the
      integration of time-dependent fluorescence tomography system within a commercial
      microPET/CT scanner for multimodality small animal imaging.

PMID- 23171510
TI  - Zoonotic transmission of pathogens by Ixodes ricinus ticks, Romania.

PMID- 23171511
TI  - Neurosyphilis presenting with unusual hippocampal abnormalities on magnetic
      resonance imaging and positron emission tomography scans: a case report.
AB  - INTRODUCTION: The incidence of neurosyphilis has declined markedly since the
      introduction of penicillin therapy. While there are a number of case reports in
      the literature of neurosyphilis causing focal decreased 18F-fluorodeoxyglucose
      uptake on positron emission tomography/computed tomography scans, to the best of
      our knowledge this is the first published report of neurosyphilis presenting with
      intensely increased 18F-fluorodeoxyglucose uptake in the hippocampus. CASE
      PRESENTATION: A 55-year-old Caucasian man presented to our facility with acute
      collapse against a background of memory difficulties over the previous six
      months. The results of his initial physical examination were normal. He scored 24
      out of 30 on the Montreal Cognitive Assessment test. A magnetic resonance imaging
      scan of his brain revealed high T2 signal intensity and atrophy within the right
      frontal area in addition to high T2 signal intensity in the bilateral mesial
      temporal areas. Blood and cerebrospinal fluid analysis revealed an active
      syphilis infection. An 18F-fluorodeoxyglucose positron emission tomography brain
      scan showed intensely increased 18F-fluorodeoxyglucose uptake limited to the head
      of the right hippocampus. He responded to penicillin treatment with an
      improvement in his cognition, which was further reflected in a complete
      resolution of the findings previously seen on magnetic resonance imaging and 18F
      fluorodeoxyglucose positron emission tomography scans. CONCLUSIONS: Diagnosis of
      neurosyphilis can be difficult, as many patients are either asymptomatic or
      present with non-specific symptoms such as memory disturbance or seizures. This
      report highlights the importance of considering neurosyphilis in the differential
      diagnosis when mesiotemporal changes are seen on magnetic resonance imaging or
      18F-fluorodeoxyglucose positron emission tomography scans.

PMID- 23171512
TI  - Arctic-like rabies virus, Bangladesh.
AB  - Arctic/Arctic-like rabies virus group 2 spread into Bangladesh ~32 years ago.
      Because rabies is endemic to and a major public health problem in this country,
      we characterized this virus group. Its glycoprotein has 3 potential N
      glycosylation sites that affect viral pathogenesis. Diversity of rabies virus
      might have public health implications in Bangladesh.

PMID- 23171513
TI  - Developing a survey of barriers and facilitators to recruitment in randomized
      controlled trials.
AB  - BACKGROUND: Recruitment to randomized controlled trials is known to be
      challenging. It is important to understand and identify predictors of good or
      poor accrual to a clinical trial so that appropriate strategies can be put in
      place to overcome these problems and facilitate successful trial completion. We
      have developed a survey tool to establish the recruitment experience of clinical
      teams regarding facilitators and barriers to recruitment in a clinical trial and
      describe herein the method of developing the questionnaire. METHODS: A literature
      search was conducted to identify studies that have explored facilitators and
      barriers to recruitment, and a list of potential factors affecting recruitment to
      a clinical trial was generated. These factors were categorized in terms relating
      to the (i) trial, (ii) site, (iii) patient, (iv) clinical team, (v) information
      and consent and (vi) study team. A list was provided for responders to grade
      these factors as weak, intermediate or strong facilitators or barriers to
      recruitment. RESULTS: A web-based survey questionnaire was developed. This survey
      was designed to establish the recruitment experience of clinical teams with
      regard to the perceived facilitators and barriers to recruitment, to identify
      strategies applied to overcome these problems, and to obtain suggestions for
      change in the organization of future trials. The survey tool can be used to
      assess the recruitment experience of clinical teams in a single/multicenter trial
      in any clinical setting or speciality involving adults or children either in an
      ongoing trial or at trial completion. The questionnaire is short, easy to
      administer and to complete, with an estimated completion time of 11 minutes.
      CONCLUSIONS: We have presented a robust methodology for developing this survey
      tool that provides an evidence-based list of potential factors that can affect
      recruitment to a clinical trial. We recommend that all clinical trialists should
      consider using this tool with appropriate trial-specific adaptations to monitor
      and improve recruitment performance in an ongoing trial or conduct the survey at
      trial completion to gather information on facilitators and barriers to
      recruitment that can form the basis of interventions and strategies to improve
      recruitment to future clinical trials.

PMID- 23171514
TI  - Childhood and adult trauma both correlate with dorsal anterior cingulate
      activation to threat in combat veterans.
AB  - BACKGROUND: Prior studies of adult post-traumatic stress disorder (PTSD) suggest
      abnormal functioning of prefrontal and limbic regions. Cumulative childhood and
      adult trauma exposures are major risk factors for developing adult PTSD, yet
      their contribution to neural dysfunction in PTSD remains poorly understood. This
      study aimed to examine the neural correlates of childhood and adult trauma
      exposure and post-traumatic stress symptoms (PTSS) within a single model. Method
      Medication-free male combat veterans (n = 28, average age 26.6 years) with a wide
      range of PTSS were recruited from the community between 2010 and 2011. Subjects
      completed an emotional face-morphing task while undergoing functional magnetic
      resonance imaging (fMRI). Clinical ratings included the Clinician-Administered
      PTSD Scale (CAPS), Childhood Trauma Questionnaire (CTQ) and Combat Exposure Scale
      (CES). A priori regions were examined through multivariate voxelwise regression
      in SPM8, using depressive symptoms and IQ as covariates. RESULTS: In the angry
      condition, CAPS scores correlated positively with activation in the medial
      prefrontal cortex [mPFC; Brodmann area (BA) 10, z = 3.51], hippocampus (z =
      3.47), insula (z = 3.62) and, in earlier blocks, the amygdala. CES and CTQ
      correlated positively with activation in adjacent areas of the dorsal anterior
      cingulate cortex (dACC; BA 32, z = 3.70 and BA 24, z = 3.88 respectively). In the
      happy condition, CAPS, CTQ and CES were not correlated significantly with
      activation patterns. CONCLUSIONS: dACC activation observed in prior studies of
      PTSD may be attributable to the cumulative effects of childhood and adult trauma
      exposure. By contrast, insula, hippocampus and amygdala activation may be
      specific to PTSS. The specificity of these results to threat stimuli, but not to
      positive stimuli, is consistent with abnormalities in threat processing
      associated with PTSS.

PMID- 23171515
TI  - Soybean isoflavone reduces the residue of zearalenone in the muscle and liver of
      prepubertal gilts.
AB  - The aim of the present study was to evaluate the protective effects of isoflavone
      (ISO) against zearalenone (ZEA) residues in the muscle and liver tissues of
      prepubertal gilts. Seventy 75-day-old, prepubertal, female pigs (Duroc * Landrace
      * Yorkshire, 26.5 +/- 0.60 kg) were allocated randomly to seven diet treatments
      for 21days as follows: one control group (fed the basal diet) and six groups fed
      the basal diet with the addition of either 0.5 or 2.0 mg/kg ZEA plus either 0,
      300 or 600 mg/kg ISO. The results showed that the diet with 2.0 mg/kg ZEA added
      caused an increase of ZEA residue level in muscle tissue (P < 0.05), and that the
      addition of both 0.5 and 2.0 mg/kg ZEA increased the residue level of ZEA in the
      liver of prepubertal gilts (P < 0.05). Addition of 600 mg/kg ISO to 2.0 mg/kg ZEA
      contaminated diet decreased the ZEA residue level in liver tissue (P < 0.05), and
      the addition of 300 or 600 mg/kg ISO to the 2.0 mg/kg ZEA-contaminated diet
      decreased the residue levels of ZEA in muscle tissue (P < 0.05). Western blot
      analysis demonstrated that feeding ZEA to prepubertal gilts increased their
      protein expression of 3alpha/3beta-hydroxysteroid dehydrogenase (HSD; P < 0.05),
      and that the addition of 300 or 600 mg/kg ISO to the 2.0 mg/kg ZEA-contaminated
      diet decreased the protein expression of 3alpha/3beta-HSD (P < 0.05), compared
      with the addition of 2.0 mg/kg ZEA alone. The results demonstrated that muscle
      and liver tissues retain residual ZEA when pigs are fed a diet contaminated with
      high concentrations of ZEA, and that the concentration of ZEA in muscle and liver
      tissues increased with increased amounts of ZEA in the feed. In diets
      contaminated with high levels of ZEA, the addition of ISO may accelerate the
      biotransformation and degradation of ZEA and its metabolites, and reduce the
      residues of ZEA in liver and muscle tissues of prepubertal gilts.

PMID- 23171516
TI  - Is coronary artery bypass grafting an acceptable alternative to myotomy for the
      treatment of myocardial bridging?
AB  - A best evidence topic in cardiothoracic surgery was written according to a
      structured protocol. The question addressed was 'Is CABG an effective alternative
      for the treatment of myocardial bridging?' Altogether, only six papers were
      identified using the reported search that represented the best evidence to answer
      the clinical question. The authors, journal, date and country of publication,
      patient group studied, study type, relevant outcomes, and results of these papers
      are tabulated; these studies reported the outcome of myotomy and coronary artery
      bypass grafting (CABG) for myocardial bridging. All of these studies were
      retrospective reports of the results of surgical intervention in patients with
      myocardial bridging. They showed that the incidence of myocardial bridging was
      less than 1-1.5% in patients with angina requiring angiography, and 7-9% of these
      patients had refractory angina despite medical treatment and required surgery.
      The evidence on the treatment of this congenital condition that mainly affects
      the middle segment of left anterior descending artery is limited, and there are
      no treatment guidelines currently available. Stenting of the tunnelled segment
      has shown high failure rates in approximately half of the cases. Current evidence
      in the literature suggests that surgery is the mainstay treatment for myocardial
      bridging. Surgery is performed either as supra-arterial myotomy and de-roofing of
      the muscle bands on- or off-pump, or as coronary artery bypass grafting of the
      affected coronary artery beyond the tunnelled segment. Although no mortality was
      reported with either of these operations, surgical myotomy on deep and extensive
      myocardial bridges carries the risk of entering the right ventricle, bleeding and
      aneurysm formation. In addition, in a small percentage of the patients undergoing
      myotomy, angina recurred. Despite the possibility of competitive flow in the
      native coronary artery after CABG for myocardial bridging, we did not identify
      any evidence demonstrating graft occlusion after CABG for myocardial bridging. In
      conclusion, in extensive and deep myocardial bridgings, CABG may be the treatment
      of choice that carries low risk, limited complications and excellent symptomatic
      relief.

PMID- 23171517
TI  - Multimodal therapy of malignant pleural mesothelioma: is the replacement of
      radical surgery imminent?
AB  - OBJECTIVES: Malignant pleural mesothelioma (MPM) remains an aggressive thoracic
      malignancy associated with poor prognosis. There is no standard treatment
      regimen, and particularly, the impact of radical surgery remains controversial.
      The main goal of our retrospective single-centre study was to evaluate the
      surgical and non-surgical treatment modalities applied at our division regarding
      their effect on the patient's survival. METHODS: During the last decade, 82
      patients with histologically confirmed MPM were treated at our division. The
      complete clinical records of 61 patients were eligible for statistical
      evaluation. RESULTS: There were 14 women (23%) and 47 men (77%) with a mean age
      of 63.7 years. Epitheloid subtype was found in 48 patients (78.7%), sarcomatoid
      in 3 (4.9%) and biphasic in 10 (16%). Surgery as the first treatment modality was
      performed in 44 patients (72.1%). Pleurectomy/decortication was done in 28 cases
      (45.9%), extended pleurectomy/decortication was performed in 13 (21.3%) and
      extrapleural pneumonectomy in 3 (4.9%). Additional intraoperative photodynamic
      therapy was administered in 20 patients, 34 underwent chemotherapy (55.7%) and 12
      had radiotherapy (19.7%). Mean survival time for the collective was 18.3 months.
      Five-year survival was 17% in the epitheloid histology group, where patients
      treated with chemotherapy alone yielded a significant increase in survival (P =
      0.049), and those with other subtypes survived for a maximum of 20.6 months.
      CONCLUSIONS: Chemotherapy and pleurectomy/decortication can extend the survival
      time of patients with MPM remarkably. The adequate treatment options have to be
      tailored to the specific particular needs of each patient considering
      histological subtype, tumour stage and patient's individual functional assessment
      as well as comorbidity.

PMID- 23171518
TI  - Prion in saliva of bovine spongiform encephalopathy-infected cattle.

PMID- 23171519
TI  - Influence of the provision of natural light and straw bales on activity levels
      and leg health in commercial broiler chickens.
AB  - The aim of this study was to assess the effect of natural light and straw bales
      on activity levels and leg health in commercial broiler chickens. Houses
      containing ~23 000 broiler chickens were assigned to one of four treatments in a
      2 * 2 factorial design. Treatments involved two levels of access to natural light
      (NL) (present '+NL', or absent '-NL') and two levels of access to straw bales
      (SB) (present (30/house) '+SB', or absent '-SB'). All houses were windowed and
      artificially lit, and windows were shuttered where appropriate. Treatments were
      applied in one of the two houses on each of the two farms, and were replicated
      over four production cycles. Behaviour was observed in 2 to 6 weeks of the cycle.
      This involved observations of general behaviour and activity, gait scores (0
      (perfect) to 5 (unable to walk)) and latency to lie (measured in seconds from
      encouraging a bird to stand). Production performance and environmental parameters
      were also measured. Average daytime light intensity and UV levels in the +NL
      treatment were 85.2 lx and 3.37 MUW/cm2, respectively, and in the -NL treatment
      were 11.4 lx and 0 MUW/cm2, respectively. Litter moisture levels were lower with
      NL treatment (P < 0.05), but were not affected by SB (P > 0.05). The percentage
      of time spent lying was significantly reduced by the provision of NL (P < 0.01),
      but not by SB (P > 0.05). There were three-way interactions between NL, SB and
      bird age on the percentage of time spent in locomotion (P < 0.05) and idling (P <
      0.05). Both treatment factors had inconsistent effects on these parameters across
      different weeks. Levels of preening, resting and aggressive behaviour were not
      affected by treatment (P > 0.05). There was an interaction between treatments in
      average gait scores, with higher scores in the -NL-SB treatment than in all other
      treatments, and higher in the -NL+SB treatment than in the +NL treatments (P <
      0.001). Average latency to lie was significantly higher with NL (P < 0.001) and
      SB (P < 0.05). We conclude that environmental modifications have the potential to
      increase activity levels and improve the leg health of commercial broilers. The
      light environment appears to be particularly important in this respect.

PMID- 23171520
TI  - Inhibition of MMP-9 activity following hypoxic ischemia in the developing brain
      using a highly specific inhibitor.
AB  - Perinatal hypoxic ischemic (HI) brain injury is a leading cause of long-term
      neurological handicap in newborn babies. Recently, excessive activity of matrix
      metalloproteinases (MMPs), and in particular MMP-9, has been implicated in the
      aetiology of HI injuries to the immature brain. Our previous study suggested that
      MMP-9 may be involved in the development of the delayed injury processes
      following HI injury to the developing brain. Given this, we therefore propose
      that MMP-9 may be a useful target for rescue therapies in the injured developing
      brain. To address this, we chose to use SB-3CT, a highly selective inhibitor that
      is known to target only MMP-2 and MMP-9, to attenuate the elevated MMP-9 activity
      seen following HI injury to the developing brain. Twenty-one-day-old postnatal
      Wistar rats were subjected to unilateral carotid artery occlusion followed by
      exposure to hypoxia (8% oxygen for 1 h). SB-3CT (50 mg/kg body weight in 25%
      dimethyl sulphoxide/75% polyethylene glycol) or an equal volume of vehicle or
      saline diluent was then administered intraperitoneally at 2, 5 and 14 h following
      the insult. Gelatin zymography revealed that pro-MMP-9 levels were significantly
      reduced at 6 h following hypoxic ischaemia (p <= 0.05). However, our results
      showed that despite significantly inhibiting brain pro-MMP-9 activity after
      hypoxic ischaemia, SB-3CT failed to confer significant neuroprotection in
      postnatal day 21 rats 3 days after an HI insult. Further investigations are
      warranted using a recently reported selective water-soluble version of SB-3CT or
      another MMP-9 selective inhibitor to resolve the role of MMP-9 in the aetiology
      of HI injury in the developing brain.

PMID- 23171521
TI  - Large-scale and uniform preparation of pure-phase wurtzite GaAs NWs on non
      crystalline substrates.
AB  - One of the challenges to prepare high-performance and uniform III-V
      semiconductor nanowires (NWs) is to control the crystal structure in large-scale.
      A mixed crystal phase is usually observed due to the small surface energy
      difference between the cubic zincblende (ZB) and hexagonal wurtzite (WZ)
      structures, especially on non-crystalline substrates. Here, utilizing Au film as
      thin as 0.1 nm as the catalyst, we successfully demonstrate the large-scale
      synthesis of pure-phase WZ GaAs NWs on amorphous SiO2/Si substrates. The obtained
      NWs are smooth, uniform with a high aspect ratio, and have a narrow diameter
      distribution of 9.5 +/- 1.4 nm. The WZ structure is verified by crystallographic
      investigations, and the corresponding electronic bandgap is also determined to be
      approximately 1.62 eV by the reflectance measurement. The formation mechanism of
      WZ NWs is mainly attributed to the ultra-small NW diameter and the very narrow
      diameter distribution associated, where the WZ phase is more thermodynamically
      stable compared to the ZB structure. After configured as NW field-effect
      transistors, a high ION/IOFF ratio of 104 - 105 is obtained, operating in the
      enhancement device mode. The preparation technology and good uniform performance
      here have illustrated a great promise for the large-scale synthesis of pure phase
      NWs for electronic and optical applications.

PMID- 23171522
TI  - No evidence of prolonged Hendra virus shedding by 2 patients, Australia.
AB  - To better understand the natural history of Hendra virus infection and its
      tendency to relapse, 2 humans infected with this virus were monitored after acute
      infection. Virus was not detected in blood samples when patients were followed-up
      at 2 and 6 years. Thus, no evidence was found for prolonged virus shedding.

PMID- 23171523
TI  - Photoplethysmographic signals and blood oxygen saturation values during
      artificial hypothermia in healthy volunteers.
AB  - Pulse oximetry utilizes the technique of photoplethysmography to estimate
      arterial oxygen saturation (SpO(2)) values. During hypothermia, the amplitude of
      the photoplethysmograph (PPG) is compromised which can lead to inaccurate
      estimation of SpO(2). A new mutlimode PPG/pulse oximeter sensor was developed to
      investigate the behaviour of PPGs during conditions of induced hypothermia (hand
      immersed in an ice bath). PPG measurements from 20 volunteers were conducted and
      SpO(2) values were estimated at all stages of the experiment. Good quality PPG
      signals were observed from the majority of the volunteers at almost all hand
      temperatures. At low temperature ranges, from 13 to 21  degrees C, the failure
      rate to estimate SpO(2) values from the multimode transreflectance PPG sensor was
      2.4% as compared to the commercial pulse oximeter with a failure rate of 70%.

PMID- 23171525
TI  - Traumatic spinal fracture treated by vertebroplasty: a case report.
AB  - INTRODUCTION: Surgical treatment for lumbar burst fractures is complex and
      typically involves either a retroperitoneal corpectomy and/or a posterior pedicle
      screw fixation. We describe the case of a patient with a lumbar burst fracture
      who was cured via a less invasive approach that has not been previously reported
      as standalone treatment. CASE PRESENTATION: This 25-year-old Caucasian man
      presented with excruciating axial low back pain exacerbated by any attempt to
      elevate the head of the bed after a motor vehicle accident. Computed tomography
      demonstrated a burst L4 fracture without spinal canal compromise. The patient
      underwent a bilateral vertebroplasty with an injectable polymer that mimics
      cortical bone. Postoperatively, the patient was progressively mobilized in a
      thoracolumbar spinal orthosis brace without any recurrence of pain. Postoperative
      computed tomography showed no loss of height in the L4 vertebral body. At one
      year postoperatively, the patient was symptom free and the computed tomography
      scan showed good fracture healing. CONCLUSION: Retroperitoneal corpectomy and/or
      posterior multi-segment fixation for lumbar burst fractures without neural
      compression in young patients are associated with loss of mobility and potential
      future adjacent level disease. Our limited vertebroplasty intervention with close
      postoperative clinical monitoring has not been previously described as standalone
      treatment, and it offers the advantages of less operative morbidity and
      maintenance of lumbar mobility in selected patients.

PMID- 23171524
TI  - The effect of a patient-oriented treatment decision aid for risk factor
      management in patients with diabetes (PORTDA-diab): study protocol for a
      randomised controlled trial.
AB  - BACKGROUND: To improve risk factor management in diabetes, we need to support
      effective interactions between patients and healthcare providers. Our aim is to
      develop and evaluate a treatment decision aid that offers personalised
      information on treatment options and outcomes, and is intended to empower
      patients in taking a proactive role in their disease management. Important
      features are: (1) involving patients in setting goals together with their
      provider; (2) encourage them to prioritise on treatments that maximise relevant
      outcomes; and (3) integration of the decision aid in the practice setting and
      workflow. As secondary aim, we want to evaluate the impact of different
      presentation formats, and learn more from the experiences of the healthcare
      providers and patients with the decision aid. METHODS AND DESIGN: We will conduct
      a randomised trial comparing four formats of the decision aid in a 2 * 2
      factorial design with a control group. Patients with type 2 diabetes managed in
      18 to 20 primary care practices in The Netherlands will be recruited. Excluded
      are patients with a recent myocardial infarction, stroke, heart failure, angina
      pectoris, terminal illness, cognitive deficits, > 65 years at diagnosis, or not
      able to read Dutch. The decision aid is offered to the patients immediately
      before their quarterly practice consultation. The same decision information will
      be available to the healthcare provider for use during consultation. In addition,
      the providers receive a set of treatment cards, which they can use to discuss the
      benefits and risks of different options. Patients in the control group will
      receive care as usual. We will measure the effect of the intervention on patient
      empowerment, satisfaction with care, beliefs about medication, negative emotions,
      health status, prescribed medication, and predicted cardiovascular risk. Data
      will be collected with questionnaires and automated extraction from medical
      records in 6 months before and after the intervention. DISCUSSION: This decision
      aid is innovative in supporting patients and their healthcare providers to make
      shared decisions about multiple treatments, using the patient's data from
      electronic medical records. The results can contribute to the further development
      and implementation of electronic decision support tools for the management of
      chronic diseases. TRIAL REGISTRATION: Dutch Trial register NTR1942.

PMID- 23171526
TI  - Using gene expression data to identify certain gastro-intestinal diseases.
AB  - BACKGROUND: Inflammatory bowel diseases, ulcerative colitis and Crohn's disease
      are considered to be of autoimmune origin, but the etiology of irritable bowel
      syndrome remains elusive. Furthermore, classifying patients into irritable bowel
      syndrome and inflammatory bowel diseases can be difficult without invasive
      testing and holds important treatment implications. Our aim was to assess the
      ability of gene expression profiling in blood to differentiate among these
      subject groups. METHODS: Transcript levels of a total of 45 genes in blood were
      determined by quantitative real-time polymerase chain reaction (RT-PCR). We
      applied three separate analytic approaches; one utilized a scoring system derived
      from combinations of ratios of expression levels of two genes and two different
      support vector machines. RESULTS: All methods discriminated different subject
      cohorts, irritable bowel syndrome from control, inflammatory bowel disease from
      control, irritable bowel syndrome from inflammatory bowel disease, and ulcerative
      colitis from Crohn's disease, with high degrees of sensitivity and specificity.
      CONCLUSIONS: These results suggest these approaches may provide clinically useful
      prediction of the presence of these gastro-intestinal diseases and syndromes.

PMID- 23171527
TI  - Ovarian adenofibromas and cystadenofibromas: magnetic resonance imaging findings
      including diffusion-weighted imaging.
AB  - BACKGROUND: Ovarian adenofibromas (AF) and cystadenofibromas (CAF) belong to the
      surface epithelial-stromal tumors, and may appear as solid, or solid and cystic
      masses mimicking ovarian cancers. PURPOSE: To evaluate the capability of magnetic
      resonance imaging (MRI) including diffusion-weighted imaging (DWI) with apparent
      diffusion coefficient (ADC) measurement for the diagnosis of ovarian AF/CAF.
      MATERIAL AND METHODS: Magnetic resonance manifestations of 13 cases of ovarian
      AF/CAF were retrospectively evaluated. DWI was obtained in all 13 lesions, and
      mean ADC values in 11 lesions were compared with those in solid portions of 27
      ovarian cancers. Results Neither case with AF/CAF revealed high signal intensity
      on DWI, whereas all ovarian cancers showed high signal intensity on DWI. The ADC
      values in the solid portions of AF/CAF were significantly higher than those of
      ovarian cancers (P < 0.001). A cut-off value of 1.20 * 10(-3) mm(2)/s for AF/CAF
      had a sensitivity of 82%, specificity of 93%, positive predictive value of 82%,
      and negative predictive value of 93%. CONCLUSION: DWI with ADC measurement may be
      helpful in differentiating AF/CAF from ovarian cancers.

PMID- 23171528
TI  - Sorafenib suppresses the rapid progress of hepatocellular carcinoma after
      insufficient radiofrequency ablation therapy: an experiment in vivo.
AB  - BACKGROUND: Radiofrequency ablation (RFA) is a widely applied treatment for
      hepatocellular carcinoma (HCC), but insufficient RFA can promote rapid
      progression of the residual tumor through the hypoxia inducible factor-1alpha
      (HIF-1alpha)/vascular endothelial growth factor A (VEGFA) pathway. Although
      sorafenib has been successfully applied to advanced HCC, the use of sorafenib in
      residual tumor cells after RFA has rarely been tested. PURPOSE: To evaluate the
      potential role of sorafenib as an adjunct to RFA to reduce the recurrence rate
      after insufficient RFA. MATERIAL AND METHODS: Xenograft tumors of SMMC 7721 were
      created by subcutaneously inoculating nude mice with hepatoma cells (5 * 10(6)
      cells per mouse). Fourteen days after inoculation, all mice were divided into
      three groups (control group [sham puncture], RFA group, and RFA combined with
      sorafenib treatment group) with six mice in each group. Each group was given a
      different treatment procedure. After treatment, the volume of the tumors was
      calculated from the resected specimens. The mRNA and protein expression of HIF
      1alpha and VEGFA was quantified by real-time PCR and immunohistochemistry
      analysis. The micro-vessel density (MVD) was determined by CD34
      immunohistochemistry. RESULTS: Real-time PCR and immunohistochemistry analysis
      showed that, compared to the RFA group, HIF-1alpha and VEGFA expression were
      significantly decreased in the group that received RFA combined with sorafenib
      treatment (P < 0.05). By comparing the control group with the RFA group, we found
      that insufficient RFA promoted HIF-1alpha and VEGFA expression (P < 0.05).
      Similar results were obtained for MVD expression. Additionally, the combination
      of RFA with sorafenib therapy resulted in a synergistic reduction in tumor growth
      compared to insufficient RFA and sham puncture (P < 0.05). CONCLUSION: Sorafenib
      was able to inhibit the expression of HIF-1alpha and VEGFA, and sorafenib was
      able to increase time to recurrence when used as an adjunct to RFA.

PMID- 23171529
TI  - Dual-source CT coronary angiography involving injection protocol with iodine load
      tailored to patient body weight and body mass index: estimation of optimal
      contrast material dose.
AB  - BACKGROUND: Body mass index (BMI) has a positive linear influence on arterial
      attenuation at coronary CT angiography involving injection protocol with dose
      linearly tailored to body weight (BW). Excessive contrast material may
      inadvertently be given in heavier patients when the dose is determined by BW
      only. PURPOSE: To investigate the effect of injection protocol with dose of
      contrast material (CM) tailored to BW and BMI on coronary arterial attenuation,
      contrast-to-noise ratio, and image noise at dual-source CT coronary angiography
      (DSCT-CA). MATERIAL AND METHODS: A total of 233 consecutive patients (mean age,
      60.2 years) undergoing DSCT-CA were included. Image acquisition protocol was
      standardized (120 kV, 380 mAs, and retrospective electrocardiograph-triggered
      DSCT-CA). CM dosage calculation was randomly categorized into groups: a BW group
      and a BW-BMI group. CM flow rate in both groups was calculated as dosage divided
      by scan time plus 8 s. Correlations between BW, BMI, and attenuations of
      ascending aorta (AA) above coronary ostia, left main coronary artery (LM),
      proximal right coronary artery (RCA), left anterior descending (LAD), and left
      circumflex artery (LCX), contrast to noise ratio of LM (LMCNR) and RCA (RCACNR),
      and image noise were evaluated with simple linear regression for two groups
      individually. RESULTS: In BW group, attenuations of AA and coronary arteries
      showed positive linear correlations to BW and BMI. In contrast, no relationships
      were found in BW-BMI group. LMCNR and RCACNR were inversely determined by BW and
      BMI in both groups. Image noise increased with BW and BMI increasing in two
      groups. CONCLUSION: BMI has a positive linear influence on arterial attenuation
      with fixed iodine per BW. The injection protocol with CM dose tailored to BW and
      BMI is reasonable during DSCT-CA.

PMID- 23171531
TI  - Importance of hypolimnetic cycling in aging of "new" mercury in a northern
      temperate lake.
AB  - The aging of "new" mercury (Hg) was investigated in Experimental Lake 658 as part
      of the Mercury Experiment To Assess Atmospheric Loading In Canada and the United
      States (METAALICUS). Mercury enriched in (202)Hg was added to the epilimnion over
      a three-year period to simulate direct atmospheric deposition. We evaluated the
      aging of newly added mercury (HgLake) in the water column using chemical methods
      and experiments to examine differences in phase partitioning and transport
      compared to the ambient pool, HgAmb. Aging was sufficiently slow to observe
      differences in the partitioning characteristics of HgLake and HgAmb. Amended
      HgLake initially partitioned to a greater extent to epilimnetic particulate
      matter (log Kd of HgLake=5.08; log Kd of HgAmb=4.9). HgLake was transported
      rapidly to the hypolimnion by settling particulate matter. Partitioning became
      more similar after amended Hg was recycled within the hypolimnion through redox
      processes. Experiments showed the removal of Hg from the aqueous phase by Fe
      and/or Mn oxyhydroxide-organic matter complexes. Separations using the anion
      exchange resin DEAE indicated that both HgLake and HgAmb were associated mainly
      with dissolved organic matter (DOM) and with partial association with sulfide in
      anoxic waters, but the degree of association of HgLake with DOM was higher in
      oxic (epilimnetic) waters. In the solid phase, chemical fractionation indicated
      greater association of HgLake with organic matter, while HgAmb showed greater
      association with oxyhydroxide and inert phases. Overall, the results suggest that
      "new" Hg added from the atmosphere is initially more particle-reactive than
      ambient Hg in the epilimnion, where initial sorption/partitioning occurs mainly
      to plankton and detrital particles. Once Hg has been deposited at the sediment
      water interface, extended equilibration time in combination with microbial and
      chemical redox processes "age" the "new" Hg, and particle partitioning becomes
      similar for the added isotope and ambient pools.

PMID- 23171530
TI  - The neural basis of flashback formation: the impact of viewing trauma.
AB  - BACKGROUND: Psychological traumatic events, such as war or road traffic
      accidents, are widespread. A small but significant proportion of survivors
      develop post-traumatic stress disorder (PTSD). Distressing, sensory-based
      involuntary memories of trauma (henceforth 'flashbacks') are the hallmark symptom
      of PTSD. Understanding the development of flashbacks may aid their prevention.
      This work is the first to combine the trauma film paradigm (as an experimental
      analogue for flashback development) with neuroimaging to investigate the neural
      basis of flashback aetiology. We investigated the hypothesis that involuntary
      recall of trauma (flashback) is determined during the original event encoding.
      Method A total of 22 healthy volunteers viewed a traumatic film whilst undergoing
      functional magnetic resonance imaging (fMRI). They kept a 1-week diary to record
      flashbacks to specific film scenes. Using a novel prospective fMRI design, we
      compared brain activation for those film scenes that subsequently induced
      flashbacks with both non-traumatic control scenes and scenes with traumatic
      content that did not elicit flashbacks ('potentials'). RESULTS: Encoding of
      scenes that later caused flashbacks was associated with widespread increases in
      activation, including in the amygdala, striatum, rostral anterior cingulate
      cortex, thalamus and ventral occipital cortex. The left inferior frontal gyrus
      and bilateral middle temporal gyrus also exhibited increased activation but only
      relative to 'potentials'. Thus, these latter regions appeared to distinguish
      between traumatic content that subsequently flashed back and comparable content
      that did not. CONCLUSIONS: Results provide the first prospective evidence that
      the brain behaves differently whilst experiencing emotional events that will
      subsequently become involuntary memories - flashbacks. Understanding the neural
      basis of analogue flashback memory formation may aid the development of treatment
      interventions for this PTSD feature.

PMID- 23171532
TI  - Effect of vascular comorbidities on survival of type 2 diabetes patients on renal
      replacement therapy.
AB  - BACKGROUND: Atherosclerosis is an important predictor of mortality in patients
      with end-stage renal disease. The aim of this study was to determine how various
      vascular comorbidities such as coronary heart disease (CHD), peripheral vascular
      disease (PVD) or cerebrovascular disease (CeVD) affect survival of type 2
      diabetic patients on renal replacement therapy (RRT). METHODS: Patients who
      entered RRT because of type 2 diabetes in 2000-2008 (n = 877) were identified
      within the Finnish Registry for Kidney Diseases. The patients were followed up
      until death or end of follow-up. Survival probabilities were calculated using
      Kaplan-Meier curves. Multivariate modeling was performed using Cox regression.
      RESULTS: 41% of the patients had CHD, 27% PVD and 16% CeVD at the start of RRT.
      Patients with PVD had a 1.9-fold (95% CI 1.6-2.3) risk of death compared to those
      without PVD when adjusting for age and gender, while patients with CHD had a 1.5
      fold (95% CI 1.2-1.8) and those with CeVD a 1.4-fold (95% CI 1.1-1.8) risk
      compared to those without these diseases. The hazard ratio (HR) for death was
      highest in patients with the combination of PVD and either CHD (HR 2.8, 95% CI
      2.1-3.8) or CeVD (HR 2.9, 95% CI 1.6-5.2) as compared to patients without any
      vascular comorbidities. CONCLUSION: PVD is the vascular comorbidity that
      increases risk of death the most among patients with type 2 diabetes starting
      RRT. Prevention of PVD in this patient group would merit further studies.

PMID- 23171533
TI  - Erythropoietin non-viral gene therapy does not affect motility, viability,
      morphology or concentration of rabbit sperm.
AB  - Erythropoietin (EPO) gene therapy can be used for several purposes; however, its
      effects on reproductive performance are unknown. The aim of this study was to
      evaluate the toxicological effects of non-viral (EPO) gene transfer on sperm
      motility, viability, morphology and concentration. Rabbit EPO cDNA was cloned
      into a pTarget mammalian expression vector. Rabbits were administered with: (1)
      pTarget/EPO vector, (2) recombinant human EPO (rHuEpo) and (3) saline (control).
      Both pTarget/EPO and rHuEpo significantly increased (P < 0.05) hematocrit levels
      1 week after injection and they remained significantly higher than the control
      for up to 5 weeks (P < 0.05), showing that both EPO treatments were effective in
      stimulating the production of red blood cells in rabbits. The EPO gene transfer
      or rHuEPO administration had no significant effect (P > 0.05) on sperm motility,
      vigor, viability, concentration or morphology in the testis.

PMID- 23171534
TI  - Best current therapy for patients with malignant pleural effusion.

PMID- 23171535
TI  - Conscious attention, meditation, and bilateral information transfer.
AB  - Recent findings indicate that conscious attention is related to large-scale
      information integration of various brain regions, including both hemispheres,
      that enables integration of parallel distributed modalities of processed
      information. There is also evidence that the level of information transference
      related to integration or splitting among brain regions, and between hemispheres,
      establishes a certain level of efficiency of the information processing. The
      level of information transference also may have modulatory influences on
      attentional capacity that are closely linked to the emotional arousal and
      autonomic response related to a stimulus. These findings suggest a hypothesis
      that changes in conscious attention, specifically during meditation could be
      reflected in the autonomic activity as the left-right information transference
      calculated from bilateral electrodermal activity (EDA). With the aim to compare
      conscious attention during meditation with other attentional states (resting
      state, Stroop task, and memory task), we performed bilateral EDA measurement in 7
      healthy persons during resting state, Stroop task, neurofeedback memory test, and
      meditation. The results indicate that the information transference (ie,
      transinformation) is able to distinguish those attentional states, and that the
      highest level of the transinformation has been found during attentional
      processing related to meditation, indicating higher level of connectivity between
      left and right sides. Calculations other than pointwise transinformation (PTI)
      performed on EDA records, such as mean skin conductance level or laterality
      index, were not able to distinguish attentional states. The results suggest that
      PTI may present an interesting method useful for the assessment of information
      flow, related to neural functioning, that in the case of meditation may reflect
      typical integrative changes in the autonomic nervous system related to brain
      functions and focused attentional processing.

PMID- 23171537
TI  - Do our ears help us cross streets safely?

PMID- 23171536
TI  - INTERBED: internet-based guided self-help for overweight and obese patients with
      full or subsyndromal binge eating disorder. A multicenter randomized controlled
      trial.
AB  - BACKGROUND: Binge eating disorder (BED) is a prevalent clinical eating disorder
      associated with increased psychopathology, psychiatric comorbidity, overweight
      and obesity, and increased health care costs. Since its inclusion in the DSM-IV,
      a few randomized controlled trials (RCTs) have suggested efficacy of book-based
      self-help interventions in the treatment of this disorder. However, evidence from
      larger RCTs is needed. Delivery of self-help through new technologies such as the
      internet should be investigated in particular, as these approaches have the
      potential to be more interactive and thus more attractive to patients than book
      based approaches. This study will evaluate the efficacy of an internet-based
      guided self-help program (GSH-I) and cognitive-behavioral therapy (CBT), which
      has been proven in several studies to be the gold standard treatment for BED, in
      a prospective multicenter randomized trial. METHODS: The study assumes the
      noninferiority of GSH-I compared to CBT. Both treatments lasted 4 months, and
      maintenance of outcome will be assessed 6 and 18 months after the end of
      treatment. A total of 175 patients with BED and a body mass index between 27 and
      40 kg/m2 were randomized at 7 centers in Germany and Switzerland. A 20% attrition
      rate was assumed. As in most BED treatment trials, the difference in the number
      of binge eating days over the past 28 days is the primary outcome variable.
      Secondary outcome measures include the specific eating disorder psychopathology,
      general psychopathology, body weight, quality of life, and self-esteem.
      Predictors and moderators of treatment outcome will be determined, and the cost
      effectiveness of both treatment conditions will be evaluated. RESULTS: The
      methodology for the INTERBED study has been detailed. CONCLUSIONS: Although there
      is evidence that CBT is the first-line treatment for BED, it is not widely
      available. As BED is still a recent diagnostic category, many cases likely remain
      undiagnosed, and a large number of patients either receive delayed treatment or
      never get adequate treatment. A multicenter efficacy trial will give insight into
      the efficacy of a new internet-based guided self-help program and will allow a
      direct comparison to the evidence-based gold standard treatment of CBT in
      Germany. TRIAL REGISTRATION: Current Controlled Trials ISRCTN40484777. German
      Clinical Trial Register DRKS00000409.

PMID- 23171538
TI  - Reptile- and amphibian-associated Salmonellosis in childcare centers, United
      States.

PMID- 23171539
TI  - Measuring cerebral hemodynamics with a modified magnetoencephalography system.
AB  - Magnetoencephalography (MEG) systems are designed to noninvasively measure
      magnetic fields produced by neural electrical currents. This project examines the
      possibility of measuring hemodynamics with an MEG system that has been modified
      with dc electromagnets to measure magnetic susceptibility while maintaining the
      capability of measuring neural dynamics. A forward model is presented that
      simulates the interaction of an applied magnetic field with changes in magnetic
      susceptibility in the brain associated with hemodynamics. Model predictions are
      compared with an experiment where deionized water was pumped into an inverted
      flask under the MEG sensor array of superconducting quantum interference device
      (SQUID) gradiometers (R(2) = 0.98, p < 0.001). The forward model was used to
      simulate the SQUID readouts from hemodynamics in the scalp and brain induced by
      performing the Valsalva maneuver. Experimental human subject recordings (N = 10)
      were made from the prefrontal region during Valsalva using concurrent measurement
      with the modified MEG system and near-infrared spectroscopy (NIRS). The NIRS
      deoxyhemoglobin signal was found to correlate significantly with the SQUID
      readouts (R(2) = 0.84, p < 0.01). SQUID noise was found to increase with the
      applied field, which will need to be mitigated in future work. These results
      demonstrate the potential and technical challenges of measuring cerebral
      hemodynamics with a modified MEG system.

PMID- 23171540
TI  - The United States Chiropractic Workforce:  An alternative or complement to
      primary care?
AB  - BACKGROUND: In the United States (US) a shortage of primary care physicians has
      become evident. Other health care providers such as chiropractors might help
      address some of the nation's primary care needs simply by being located in areas
      of lesser primary care resources. Therefore, the purpose of this study was to
      examine the distribution of the chiropractic workforce across the country and
      compare it to that of primary care physicians. METHODS: We used nationally
      representative data to estimate the per 100,000 capita supply of chiropractors
      and primary care physicians according to the 306 predefined Hospital Referral
      Regions. Multiple variable Poisson regression was used to examine the influence
      of population characteristics on the supply of both practitioner-types. RESULTS:
      According to these data, there are 74,623 US chiropractors and the per capita
      supply of chiropractors varies more than 10-fold across the nation. Chiropractors
      practice in areas with greater supply of primary care physicians (Pearson's
      correlation 0.17, p-value < 0.001) and appear to be more responsive to market
      conditions (i.e. more heavily influenced by population characteristics) in
      regards to practice location than primary care physicians. CONCLUSION: These
      findings suggest that chiropractors practice in areas of greater primary care
      physician supply. Therefore chiropractors may be functioning in more
      complementary roles to primary care as opposed to an alternative point of access.

PMID- 23171541
TI  - Persistent inguinal seroma managed with sprinkling of talcum powder: a case
      report.
AB  - INTRODUCTION: We present a new method to treat recurrent seromas, which is based
      on our experience with a patient who had recurrent groin seroma and was treated
      successfully with a sprinkling of talcum powder in the seroma cavity. CASE
      PRESENTATION: A 67-year-old Caucasian man with a suprapubic recurrent right groin
      hernia underwent inguinal hernioplasty with a polypropylene plug. Three days
      later the patient presented with a right groin fluctuating mass beneath the
      surgical wound with no signs of infection, and was discharged after seroma
      aspiration. After 23 days of increasing drainage, the seroma cavity was
      thoroughly dried with clean gauze swabs, and four g of sterilized dry talcum
      powder was sprinkled into the seroma cavity with a five-cc syringe. A compressive
      dressing was placed, and the patient was discharged. One week after the
      sprinkling of talcum powder, the surgical wound was almost closed with only
      minimal oozing from the drainage incision. The patient did not report any adverse
      effects. Two weeks later, the wound was fully healed. CONCLUSION: Talcum powder
      sprinkling could be an effective, quick, and safe method for the treatment of
      inguinal seromas after inguinal hernioplasty when conservative management has
      failed. Nevertheless, larger series are needed before assessing this technique as
      the treatment of choice.

PMID- 23171542
TI  - Role of vascular endothelial growth factor and angiopoietin 1 in renal injury in
      hemolytic uremic syndrome.
AB  - BACKGROUND/AIMS: The recovery process from renal injury in hemolytic uremic
      syndrome (HUS) remains obscure. In order to clarify the role of vascular
      endothelial growth factor (VEGF) and angiopoietin 1 (Ang-1) in the renal recovery
      from HUS, we produced a model of mild HUS and examined the renal recovery
      process. METHODS: We investigated three groups of mice. Group 1 consisted of mice
      that received an injection of Shiga toxin 2 (Stx2) and lipopolysaccharide (LPS);
      group 2 consisted of mice that received an injection of low dose of Stx2 and LPS,
      and group 3 consisted of control mice. RESULTS: Serum Cr levels in group 1 were
      greater than those in group 2, and all mice in group 1 died, whereas all mice in
      group 2 remained alive. Endothelial injury at 24 h in group 1 was higher than in
      group 2. Electron-microscopic findings demonstrated that the endothelial cells
      formed immature capillary-like lumina from 7 to 28 days with increases in the
      expression of CD31-positive cells. Glomerular VEGF expression decreased at 72 h
      in group 1, but gradually increased in group 2. Glomerular Ang-1 expression
      peaked from 72 h to 28 days. Ang-1 expression was frequently found in the
      endothelial cell region of vesicle walls simultaneous with increased CD31
      positive staining. CONCLUSION: Our findings suggest that VEGF and Ang-1 play
      important roles in the recovery process, particularly in the regeneration of
      endothelial injury.

PMID- 23171543
TI  - Composition profiling of inhomogeneous SiGe nanostructures by Raman spectroscopy.
AB  - In this work, we present an experimental procedure to measure the composition
      distribution within inhomogeneous SiGe nanostructures. The method is based on the
      Raman spectra of the nanostructures, quantitatively analyzed through the
      knowledge of the scattering efficiency of SiGe as a function of composition and
      excitation wavelength. The accuracy of the method and its limitations are
      evidenced through the analysis of a multilayer and of self-assembled islands.

PMID- 23171544
TI  - Differentiation of prions from L-type BSE versus sporadic Creutzfeldt-Jakob
      disease.
AB  - We compared transmission characteristics for prions from L-type bovine spongiform
      encephalopathy and MM2-cortical sporadic Creutzfeldt-Jakob disease in the Syrian
      golden hamster and an ovine prion protein-transgenic mouse line and isolated
      distinct prion strains. Our findings suggest the absence of a causal relationship
      between these diseases, but further investigation is warranted.

PMID- 23171545
TI  - Nanographene oxide-based radioimmunoconstructs for in vivo targeting and SPECT
      imaging of HER2-positive tumors.
AB  - Nanographene oxide (NGO) is a novel nano-wall material that tracks to tumors in
      vivo, and which, as a consequence of its large surface area, has the capacity to
      carry a large payload. This study explores the use of anti-HER2 antibody
      (trastuzumab)-conjugated NGO, radiolabeled with (111)In-benzyl
      diethylenetriaminepentaacetic acid (BnDTPA) via pipi-stacking, for functional
      imaging. In two HER2-overexpressing murine models of human breast cancer, high
      tumor-to-muscle ratio was achieved, resulting in clear visualization of tumor
      using single-photon emission computed tomography (SPECT). In the BALB/neuT model
      and in BALB/c nu/nu mice bearing 231/H2N xenografts, tumor accumulation amounted
      to 12.7 +/- 0.67 and 15.0 +/- 3.7% of the injected dose/g (%ID/g) of tumor tissue
      at 72 h, with tumor-to-muscle ratios of 35:1 and 7:1, respectively. Radiolabeled
      NGO-trastuzumab conjugates demonstrated superior pharmacokinetics compared to
      radiolabeled trastuzumab without NGO, with more rapid clearance from the
      circulation. The use of NGO as a scaffold to build radiolabeled nano
      immunoconstructs holds promise for molecular imaging of tumors.

PMID- 23171546
TI  - The combined treatment of calcium ionophore with strontium improves the quality
      of ovine SCNT embryo development.
AB  - Summary Poor embryo quality is a major problem that contributes to the failure of
      pregnancy in somatic cell nuclear transfer (SCNT). The aims of this study were to
      improve the quality of ovine SCNT embryos by modifying the conventional
      activation protocol with the addition of SrCl2. In order to achieve this
      objective we conducted a series of experiments with in vitro-matured oocytes to
      optimize conditions for oocyte activation with strontium, and subsequently
      applied the protocol to SCNT embryos. The results showed that in vitro-matured
      oocytes could be activated effectively by 10 mM SrCl2 + 5 mg/ml cytochalasin B
      (CB) for 5 h in the absence of Ca2+ and that the blastocyst rate on day 7 (33.2%)
      was similar to that in the control group (31.0%) (5 M calcium ionophore [IP]
      A23187 for 5 min and cultured in CB/cycloheximide [CHX] for 5 h; P > 0.05). In
      SCNT experiments, the total cell number/blastocyst (104.12 +/- 6.86) in the IP +
      SrCl2/CB-treatment group was, however, significantly higher than that in the
      control group (81.07 +/- 3.39; P < 0.05). Apoptotic index (12.29 +/- 1.22%) was
      significantly lower than the control (17.60 +/- 1.39%; P < 0.05) when a
      combination of IP and SrCl2/CB was applied to SCNT embryos. In addition,
      karyotyping of the SCNT embryos showed that the percentage of diploid blastocysts
      in the IP + SrCl2/CB-treatment group was slightly higher than that in the control
      (P > 0.05). We conclude that the modified activation protocol with IP + SrCl2/CB
      can improve significantly the quality of ovine SCNT embryos in terms of total
      cell number, apoptosis and ploidy.

PMID- 23171547
TI  - The Peri/postnatal Epigenetic Twins Study (PETS).
AB  - The Peri/postnatal Epigenetic Twins Study (PETS) is a longitudinal cohort of 250
      pairs of Australian twins and their mothers, who were recruited mid-way through
      pregnancy from January 2007 to September 2009. The study is centered on the
      developmental origins of health and disease paradigm (DOHaD) in which an adverse
      intrauterine environment predisposes the individual to complex disease in later
      life by reducing growth in utero and adversely altering developmental plasticity.
      Data concerning diet and lifestyle were collected from mothers during pregnancy,
      and samples of plasma and serum taken at 28 weeks' gestation. We attended 75% of
      all births, at which time we collected multiple biological samples including
      placenta, cord blood, and neonatal cheek cells, the latter from 91% of pairs.
      Chorionicity was recorded and zygosity was determined by DNA testing where
      necessary. Approximately 40% of the twins are monozygotic, two-thirds of which
      are dichorionic. Twins were seen again at 18 months of age and repeat blood and
      cheek swabs taken where possible. Studies of gene expression and the epigenetic
      marks of DNA methylation have so far revealed that twins exhibit a wide range of
      epigenetic discordance at birth, that one-third of the epigenome changes
      significantly between birth and 18 months; shared (maternal) environment, genetic
      factors, and non-shared intrauterine environment contribute to an increasing
      proportion of epigenetic variation at birth, respectively, and affect tissues
      differently, and that within-pair birth weight discordance correlates with
      epigenetic discordance in genes associated with lipid metabolism, supporting an
      epigenetic mechanism for DOHaD.

PMID- 23171548
TI  - The conserved interaction of C7orf30 with MRPL14 promotes biogenesis of the
      mitochondrial large ribosomal subunit and mitochondrial translation.
AB  - Mammalian mitochondria harbor a dedicated translation apparatus that is required
      for the synthesis of 13 mitochondrial DNA (mtDNA)-encoded polypeptides, all of
      which are essential components of the oxidative phosphorylation (OXPHOS)
      complexes. Little is known about the mechanism of assembly of the mitoribosomes
      that catalyze this process. Here we show that C7orf30, a member of the large
      family of DUF143 proteins, associates with the mitochondrial large ribosomal
      subunit (mt-LSU). Knockdown of C7orf30 by short hairpin RNA (shRNA) does not
      alter the sedimentation profile of the mt-LSU, but results in the depletion of
      several mt-LSU proteins and decreased monosome formation. This leads to a
      mitochondrial translation defect, involving the majority of mitochondrial
      polypeptides, and a severe OXPHOS assembly defect. Immunoprecipitation and mass
      spectrometry analyses identified mitochondrial ribosomal protein (MRP)L14 as the
      specific interacting protein partner of C7orf30 in the mt-LSU. Reciprocal
      experiments in which MRPL14 was depleted by small interfering RNA (siRNA)
      phenocopied the C7orf30 knockdown. Members of the DUF143 family have been
      suggested to be universally conserved ribosomal silencing factors, acting by
      sterically inhibiting the association of the small and large ribosomal subunits.
      Our results demonstrate that, although the interaction between C7orf30 and MRPL14
      has been evolutionarily conserved, human C7orf30 is, on the contrary, essential
      for mitochondrial ribosome biogenesis and mitochondrial translation.

PMID- 23171549
TI  - Reduced TOR signaling sustains hyphal development in Candida albicans by lowering
      Hog1 basal activity.
AB  - Candida albicans is able to undergo reversible morphological changes between
      yeast and hyphal forms in response to environmental cues. This morphological
      plasticity is essential for its pathogenesis. Hyphal development requires two
      temporally linked changes in promoter chromatin, which is sequentially regulated
      by temporarily clearing the transcription inhibitor Nrg1 upon activation of
      cAMP/protein kinase A and promoter recruitment of the histone deacetylase Hda1
      under reduced target of rapamycin (Tor1) signaling. The GATA family transcription
      factor Brg1 recruits Hda1 to promoters for sustained hyphal development, and BRG1
      expression is a readout of reduced Tor1 signaling. How Tor1 regulates BRG1
      expression is not clear. Using a forward genetic screen for mutants that can
      sustain hyphal elongation in rich media, we found hog1, ssk2, and pbs2 mutants of
      the HOG mitogen-activated protein kinase pathway to express BRG1 irrespective of
      rapamycin. Furthermore, rapamycin lowers the basal activity of Hog1 through the
      functions of the two Hog1 tyrosine phosphatases Ptp2 and Ptp3. Active Hog1
      represses the expression of BRG1 via the transcriptional repressor Sko1 as Sko1
      disassociates from the promoter of BRG1 in the hog1 mutant or in rapamycin. Our
      data suggest that reduced Tor1 signaling lowers Hog1 basal activity via Hog1
      phosphatases to activate BRG1 expression for hyphal elongation.

PMID- 23171550
TI  - TOR and RAS pathways regulate desiccation tolerance in Saccharomyces cerevisiae.
AB  - Tolerance to desiccation in cultures of Saccharomyces cerevisiae is inducible;
      only one in a million cells from an exponential culture survive desiccation
      compared with one in five cells in stationary phase. Here we exploit the
      desiccation sensitivity of exponentially dividing cells to understand the
      stresses imposed by desiccation and their stress response pathways. We found that
      induction of desiccation tolerance is cell autonomous and that there is an
      inverse correlation between desiccation tolerance and growth rate in glucose-,
      ammonia-, or phosphate-limited continuous cultures. A transient heat shock
      induces a 5000-fold increase in desiccation tolerance, whereas hyper-ionic, 
      reductive, -oxidative, or -osmotic stress induced much less. Furthermore, we
      provide evidence that the Sch9p-regulated branch of the TOR and Ras-cAMP pathway
      inhibits desiccation tolerance by inhibiting the stress response transcription
      factors Gis1p, Msn2p, and Msn4p and by activating Sfp1p, a ribosome biogenesis
      transcription factor. Among 41 mutants defective in ribosome biogenesis, a subset
      defective in 60S showed a dramatic increase in desiccation tolerance independent
      of growth rate. We suggest that reduction of a specific intermediate in 60S
      biogenesis, resulting from conditions such as heat shock and nutrient
      deprivation, increases desiccation tolerance.

PMID- 23171551
TI  - Notch signaling from the endosome requires a conserved dileucine motif.
AB  - Notch signaling is reliant on gamma-secretase-mediated processing, although the
      subcellular location where gamma-secretase cleaves Notch to initiate signaling
      remains unresolved. Accumulating evidence demonstrates that Notch signaling is
      modulated by endocytosis and endosomal transport. In this study, we investigated
      the relationship between Notch transport itinerary and signaling capacity. In
      doing so, we discovered a highly conserved dileucine sorting signal encoded
      within the cytoplasmic tail that directs Notch to the limiting membrane of the
      lysosome for signaling. Mutating the dileucine motif led to receptor accumulation
      in cation-dependent mannose-phosphate receptor-positive tubular early endosomes
      and a reduction in Notch signaling capacity. Moreover, truncated receptor forms
      that mimic activated Notch were readily cleaved by gamma-secretase within the
      endosome; however, the cleavage product was proteasome-sensitive and failed to
      contribute to robust signaling. Collectively these results indicate that Notch
      signaling from the lysosome limiting membrane is conserved and that receptor
      targeting to this compartment is an active process. Moreover, the data support a
      model in which Notch signaling in mammalian systems is initiated from either the
      plasma membrane or lysosome, but not the early endosome.

PMID- 23171552
TI  - Altered nitric oxide production mediates matrix-specific PAK2 and NF-kappaB
      activation by flow.
AB  - Shear stress generated by distinct blood flow patterns modulates endothelial cell
      phenotype to spatially restrict atherosclerotic plaque development. Signaling
      through p21-activated kinase (PAK) mediates several of the deleterious effects of
      shear stress, including enhanced NF-kappaB activation and proinflammatory gene
      expression. Whereas shear stress activates PAK in endothelial cells on a
      fibronectin matrix, basement membrane proteins limit shear-induced PAK activation
      and inflammation through a protein kinase A-dependent pathway; however, the
      mechanisms underlying this regulation were unknown. We show that basement
      membrane proteins limit membrane recruitment of PAK2, the dominant isoform in
      endothelial cells, by blocking its interaction with the adaptor protein Nck. This
      uncoupling response requires protein kinase A-dependent nitric oxide production
      and subsequent PAK2 phosphorylation on Ser-20 in the Nck-binding domain. Of
      importance, shear stress does not stimulate nitric oxide production in
      endothelial cells on fibronectin, resulting in enhanced PAK activation, NF-kappaB
      phosphorylation, ICAM-1 expression, and monocyte adhesion. These data demonstrate
      that differential flow-induced nitric oxide production regulates matrix-specific
      PAK signaling and describe a novel mechanism of nitric oxide-dependent NF-kappaB
      inhibition.

PMID- 23171553
TI  - Feedback inhibition of ENaC during acute sodium loading in vivo.
AB  - The epithelial Na(+) channel (ENaC) is tightly regulated by sodium intake to
      maintain whole body sodium homeostasis. In addition, ENaC is inhibited by high
      levels of intracellular Na(+) [Na(+)](i), presumably to prevent cell Na(+)
      overload and swelling. However, it is not clear if this regulation is relevant in
      vivo. We show here that in rats, an acute (4 h) oral sodium load decreases whole
      cell amiloride-sensitive currents (I(Na)) in the cortical collecting duct (CCD)
      even when plasma aldosterone levels are maintained high by infusing the hormone.
      This was accompanied by decreases in whole-kidney cleaved alpha-ENaC (2.6 fold),
      total beta-ENaC (1.7 fold), and cleaved gamma-ENaC (6.2 fold). In addition, cell
      surface beta- and gamma-ENaC expression was measured using in situ biotinylation.
      There was a decrease in cell-surface core-glycosylated (2.2 fold) and maturely
      glycosylated (4.9 fold) beta-ENaC and cleaved gamma-ENaC (4.7 fold). There were
      no significant changes for other apical sodium transporters. To investigate the
      role of increases in Na(+) entry and presumably [Na(+)](i) on ENaC, animals were
      infused with amiloride prior to and during sodium loading. Blocking Na(+) entry
      did not inhibit the effect of resalting on I(Na). However, amiloride did prevent
      decreases in ENaC expression, an effect that was not mimicked by
      hydrochlorothiazide administration. Na(+) entry and presumably [Na(+)](i) can
      regulate ENaC expression but does not fully account for the aldosterone
      independent decrease in I(Na) during an acute sodium load.

PMID- 23171556
TI  - Talc instillation consensus AIDS differentiating successful from unsuccessful
      pleurodesis: a survey on the interpretation of pleural approximation after chest
      tube placement.

PMID- 23171555
TI  - Chronic interstitial fibrosis in the rat kidney induced by long-term (6-mo)
      exposure to lithium.
AB  - There is a lack of suitable animal models that replicate the slowly progressive
      chronic interstitial fibrosis that is characteristic of many human chronic
      nephropathies. We describe a chronic long-term (6-mo) model of lithium-induced
      renal fibrosis, with minimal active inflammation, which mimics chronic kidney
      interstitial fibrosis seen in the human kidney. Rats received lithium via their
      chow (60 mmol lithium/kg food) daily for 6 mo. No animals died during the
      exposure. Nephrogenic diabetes insipidus was established by 3 wk and persisted
      for the 6 mo. Following metabolic studies, the animals were killed at 1, 3, and 6
      mo and the kidneys were processed for histological and immunohistochemical
      studies. Progressive interstitial fibrosis, characterized by increasing numbers
      of myofibroblasts, enhanced transforming growth factor-beta(1) expression and
      interstitial collagen deposition, and a minimal inflammatory cellular response
      was evident. Elucidation of the underlying mechanisms of injury in this model
      will provide a greater understanding of chronic interstitial fibrosis and allow
      the development of intervention strategies to prevent injury.

PMID- 23171554
TI  - mPGES-1-derived PGE2 mediates dehydration natriuresis.
AB  - PGE(2) is a natriuretic factor whose production is elevated after water
      deprivation (WD) but its role in dehydration natriuresis is not well-defined. The
      goal of the present study was to investigate the role of microsomal prostaglandin
      E synthase-1 (mPGES-1) in dehydration natriuresis. After 24-h WD, wild-type (WT)
      mice exhibited a significant increase in 24-h urinary Na(+) excretion accompanied
      with normal plasma Na(+) concentration and osmolality. In contrast, WD-induced
      elevation of urinary Na(+) excretion was completely abolished in mPGES-1 knockout
      (KO) mice in parallel with increased plasma Na(+) concentration and a trend
      increase in plasma osmolality. WD induced a 1.8-fold increase in urinary PGE(2)
      output and a 1.6-fold increase in PGE(2) content in the renal medulla of WT mice,
      both of which were completely abolished by mPGES-1 deletion. Similar patterns of
      changes were observed for urinary nitrate/nitrite and cGMP. The natriuresis in
      dehydrated WT mice was associated with a significant downregulation of renal
      medullary epithelial Na channel-alpha mRNA and protein, contrasting to unaltered
      expressions in dehydrated KO mice. By quantitative RT-PCR, WD increased the
      endothelial nitric oxide synthase (eNOS), inducible NOS, and neuronal NOS
      expressions in the renal medulla of WT mice by 3.9-, 1.48-, and 2.6-fold,
      respectively, all of which were significantly blocked in mPGES-1 KO mice. The
      regulation of eNOS expression was further confirmed by immunoblotting. Taken
      together, our results suggest that mPGES-1-derived PGE(2) contributes to
      dehydration natriuresis likely via NO/cGMP.

PMID- 23171557
TI  - [A woman with an abdomen filled with gas].
AB  - A 73-year-old woman diagnosed with colon carcinoma underwent right hemicolectomy.
      Postoperatively, she developed hypotension, fever, diarrhea and haematemesis.
      Gastroduodenoscopy revealed ischemia of the gastric mucosa. A CT abdomen showed
      gas in the superior mesenteric vein and the portal system. Hepatic venous portal
      gas is a rare finding, often caused by bowel ischaemia.

PMID- 23171558
TI  - [A man who became acutely agitated after injection of contrast].
AB  - A 63-year-old man attended the emergency room with lower back pain. An abdominal
      CT scan was scheduled. However, after intravenous injection of contrast, the
      patient became acutely agitated and his tension dropped. After a delay of two
      minutes the scan was performed and showed massive contrast extravasation due to a
      ruptured abdominal aortic aneurysm. Subsequently, the patient successfully
      underwent an emergency laparotomy.

PMID- 23171559
TI  - [An elderly woman with stiffness of the thumb].
AB  - A 81-year-old woman presented with progressive pain, stiffness and swelling of
      the right thumb. She also complained of dysphagia and Raynaud's phenomenon.
      Physical examination revealed sclerodactyly and telangiectasia. A plain X-ray
      showed marked calcifications of the flexor tendon of the right thumb and
      esophagography demonstrated decreased motility of the lower esophagus.
      Additionally, anticentromere antibodies were positive. As a result, the patient
      was diagnosed with calcinosis as a presenting symptom of limited systemic
      scleroderma.

PMID- 23171560
TI  - [A contractor with damaged knees].
AB  - A 51-year-old man developed burn wounds on both knees after finishing a cement
      floor. Cement burns are caused by wet cement, which is highly alkaline Initial
      treatment consists of lavage. Further management can be conservative but in full
      thickness injuries excision and grafting should be considered.

PMID- 23171561
TI  - [Burns in children: child abuse or another cause?].
AB  - Burns are common in children but it is not always clear whether the burn is
      accidental or not. Child abuse should always be considered. We present two
      children in which the diagnosis only became clear after admission and further
      investigation. Patient A, a 15-month-old boy, had a burn on his left shoulder.
      The burn was assumed suspect in view of the unclear history given by the parents
      and a possible delay in their seeking help. The patient was ultimately diagnosed
      with impetigo bullosa and successfully treated with antibiotics. Patient B, a 24
      month-old girl, had burns on both feet and her right hand, which were infected as
      a result of the delay in seeking help. The burns were identified as abuse
      related. The child was removed from her mother's care and sent to a foster home.
      A well-defined work-up should be followed in case of burns in children.

PMID- 23171562
TI  - [Ranke and modern surgery in Groningen].
AB  - Hans Rudolph Ranke (1849-1887) studied medicine in Halle, located in the eastern
      part of Germany, where he also trained as a surgeon under Richard von Volkmann
      (1830-1889), during which time he became familiar with the new antiseptic
      technique that had been introduced by Joseph Lister (1827-1912). In 1878 he was
      appointed head of the department of surgery in Groningen, the Netherlands, where
      his predecessor had been chronically indisposed and developments were flagging.
      Within a few months, Ranke had introduced disinfection by using carbolic acid
      both before and during operations. For the disinfection of wound dressings, he
      replaced carbolic acid with thymol as this was less pungent and foul-smelling.
      The rate of postoperative infections dropped to a minimum despite the inadequate
      housing and living conditions of the patients with infectious diseases. In 1887,
      at the age of 37, Ranke died after a brief illness - possibly glomerulonephritis 
      only eight years after he had assumed office. A street in the city of Groningen
      near its present-day University Medical Centre has been named after him.

PMID- 23171563
TI  - [Increasing healthcare costs in the Netherlands: the doctor's role].
AB  - The sharply increasing costs of healthcare in the Netherlands are a huge problem
      and pose a serious threat for the sustainability of care in this country. The
      question is whether all treatments really do add value. Many of the treatments
      now provided are not indicated, or are even contraindicated. Combating
      superfluous healthcare provision is an important solution for improving quality
      and reducing costs. This is the responsibility of all involved, with doctors
      playing a leading role. We propose an active role for the Royal Dutch Medical
      Association (KNMG) and all scientific associations.

PMID- 23171564
TI  - [Uterine fibroids complicated by haematometra].
AB  - BACKGROUND: Uterine fibroids are common, benign tumours of the myometrium. The
      clinical symptoms include menorrhagia, abdominal pain and subfertility. CASE
      DESCRIPTION: A 37-year-old black woman known to have uterine fibroids presented
      at the gynaecology outpatient clinic with abdominal pain. Ultrasonography and an
      MRI scan revealed haematometra caused by an obstructive myoma, which was drained
      during a hysteroscopy. The patient was subsequently treated with gonadotrophin
      releasing hormone (GnRH) agonist in order to reduce the myoma. Resection of the
      myoma will take place sometime in the future. CONCLUSION: Haematometra is an
      accumulation of blood in the uterine cavity. It is a rare complication of uterine
      fibroids and causes abdominal pain and enlargement of the uterus. Amenorrhoea is
      often a finding because an adequate outflow of menstrual blood is no longer
      possible. The primary treatment is to drain the haematometra; a subsequent
      myomectomy should be performed.

PMID- 23171565
TI  - [Developments in HPV vaccination].
AB  - Vaccination against the human papilloma virus (HPV) has been included in the
      national Vaccination Programme of the Netherlands for 12-year-old girls since
      2010. Vaccination coverage for the birth cohort of 1997 was 56.; there is a
      gradual increase in uptake. Continuous safety monitoring brought no new unknown
      serious side effects to light; many girls suffered from transient symptoms such
      as painful arm, fatigue and headache. After the current vaccines that protect
      against HPV types 2 and 4 types, respectively and induce some cross protection,
      vaccines are being developed that can induce broader protection. HPV vaccination
      of 12-year-old girls is cost-effective, even for relatively low vaccination
      coverage. The potential protection of HPV vaccination extends beyond prevention
      of cervical cancer by preventing other oncological manifestations of HPV
      infection in women as well as men and genital warts. The preventive HPV vaccines
      do not appear to be effective in treating existing abnormalities.

PMID- 23171566
TI  - [New dietary reference values vitamin D].
AB  - The benefit of vitamin D has been heavily debated over the past few years. There
      are claims that vitamin D not only fulfils a protective function for bone health,
      but for diseases such as cancer, diabetes mellitus and cardiovascular disease as
      well. The question is: to what extent have such claims been scientifically
      proven? And should people at risk of a deficiency use vitamin D supplements to be
      on the safe side, or not? The Health Council of the Netherlands evaluated the
      dietary reference values for vitamin D and the accompanying recommendations on
      supplementation.

PMID- 23171567
TI  - Effect of low-level laser therapy on pain, quality of life and sleep in patients
      with fibromyalgia: study protocol for a double-blinded randomized controlled
      trial.
AB  - BACKGROUND: Low-level laser therapy (LLLT) has been widely used as adjuvant
      strategy for treatment of musculoskeletal disorders. The light-tissue interaction
      (photobiostimulation) promotes analgesic and anti-inflammatory effects and
      improves tissue healing, which could justify the recommendation of this therapy
      for patients with fibromyalgia, leading to an improvement in pain and possibly
      minimizing social impact related to this disease. The present study proposes to
      evaluate the effect of LLLT on tender points in patients with fibromyalgia,
      correlating this outcome with quality of life and sleep. METHODS/DESIGN: One
      hundred and twenty patients with fibromyalgia will be treated at the Integrated
      Health Center and the Sleep Laboratory of the Post Graduate Program in
      Rehabilitation Sciences of the Nove de Julho University located in the city of
      Sao Paulo, Brazil. After fulfilling the eligibility criteria, a clinical
      evaluation and assessments of pain and sleep quality will be carried out and self
      administered quality of life questionnaires will be applied. The 120 volunteers
      will be randomly allocated to an intervention group (LLLT, n = 60) or control
      group (CLLLT, n = 60). Patients from both groups will be treated three times per
      week for four weeks, totaling twelve sessions. However, only the LLLT group will
      receive an energy dose of 6 J per tender point. A standardized 50-minute exercise
      program will be performed after the laser application. The patients will be
      evaluated regarding the primary outcome (pain) using the following instruments:
      visual analog scale, McGill Pain Questionnaire and pressure algometry. The
      secondary outcome (quality of life and sleep) will be assessed with the following
      instruments: Medical Outcomes Study 36-item Short-Form Health Survey,
      Fibromyalgia Impact Questionnaire, Berlin Questionnaire, Epworth Sleepiness Scale
      and polysomnography. ANOVA test with repeated measurements for the time factor
      will be performed to test between-groups differences (followed by the Tukey
      Kramer post hoc test), and a paired t test will be performed to test within-group
      differences. The level of significance for the statistical analysis will be set
      at 5% (P <= .05). TRIAL REGISTRATION: The protocol for this study is registered
      with the Brazilian Registry of Clinical Trials - ReBEC (RBR-42gkzt).

PMID- 23171568
TI  - Locking-in effects due to early interventions? An evaluation of a
      multidisciplinary screening programs for avoiding long-term sickness.
AB  - OBJECTIVE: In this article, we estimate the effect of a multidisciplinary
      collaborationprogram on the length of sickness absence. The intention with the
      programwas to avoid long-term sickness absence by providing an early and holistic
      evaluation of the sick-listed individuals' conditions. The target group was
      individuals who were at risk of becoming long-term sick. The eligibility criteria
      were mainly based on register information that we have access to. METHODS: Using
      this register information, we estimate different Cox regression models and apply
      a nonparametric matching estimator. We have also conducted a small randomized
      experiment. RESULTS: The result from the randomized experiment is not
      statistically significant, but the point estimate provides the same result as was
      found in the observational study: The program prolongs rather than shortens the
      sickness absence spell. That is, the average sickness absence spell is prolonged
      by about 3 months. CONCLUSIONS: Our main explanation for this discouraging result
      is that the team focuses too much on rehabilitation rather than encouraging the
      sick-listed individual to return to work.

PMID- 23171569
TI  - Among patients admitted to ICU, delirium is most common in those with
      neurological diagnoses, and is associated with adverse health outcomes.

PMID- 23171570
TI  - 37% of child survivors of intrauterine or neonatal insults experience at least
      one long-term sequela, the most common being neurodevelopmental delay.

PMID- 23171571
TI  - Use of antidepressants in the second trimester is associated with reduced
      pregnancy duration, and third trimester antidepressant use with infant
      convulsions.

PMID- 23171572
TI  - Wild Boars as Hosts of Human-Pathogenic Anaplasma phagocytophilum Variants.

PMID- 23171573
TI  - Persimmon fruit tannin-rich fiber reduces cholesterol levels in humans.
AB  - Bile acid-binding agents are known to lower blood cholesterol levels and have
      been clinically used for the treatment of hypercholesterolemia. We previously
      showed that tannin-rich fiber from young persimmon (Diospyros kaki) fruits had
      bile acid-binding properties. In this study, we performed a randomized, double
      blind, placebo-controlled trial to investigate the hypocholesterolemic effects of
      tannin-rich fiber in humans. The subjects (n = 40, plasma total cholesterol
      levels 180-259 mg/dl) were divided into 3 groups and ingested cookie bars
      containing 0 g (placebo group, n = 14), 3 g (low-dose group, n = 13), or 5 g
      (high-dose group, n = 13) of tannin-rich fiber 3 times daily before meals for 12
      weeks. Plasma total cholesterol levels decreased significantly in the low-dose
      (12 weeks, p < 0.005) and high-dose (6 weeks, p < 0.05; 12 weeks, p < 0.001)
      groups. In addition, plasma low-density lipoprotein cholesterol levels decreased
      significantly in the high-dose group (6 weeks, p < 0.05; 12 weeks, p < 0.001).
      These improvements were not accompanied by changes in plasma high-density
      lipoprotein cholesterol or plasma triglyceride levels. Our findings indicate that
      tannin-rich fiber from young persimmon fruits is a useful food material for
      treating hypercholesterolemia.

PMID- 23171574
TI  - At the end of a very hard day, people find some reason to believe.

PMID- 23171575
TI  - Acquired urethral diverticulum in a man with paraplegia presenting with a scrotal
      mass: a case report.
AB  - INTRODUCTION: Male urethral diverticula are rare. Patients with paraplegia may
      present with acquired diverticula as a result of prolonged catheterization.
      Diverticula may be asymptomatic or lead to lower urinary tract symptoms. Rarely,
      the diverticulum may initially present as a scrotal mass. CASE PRESENTATION: We
      report the case of a male 45-year-old Arab with paraplegia who presented with a
      mass in the peno-scrotal junction. He had in his medical history iterative
      prolonged urethral catheterizations associated with urine leakage through the
      urethral meatus upon applying compression. Diagnosis confirmation of urethral
      diverticula is obtained by retrograde urethrography. The patient underwent a
      diverticulectomy with urethroplasty. CONCLUSION: Male acquired urethral
      diverticula can be found in patients who have a spinal cord injury because of
      prolonged urethral catheterization. Clinical presentations are different and
      sometimes can be misleading. Retrograde urethrography is the key to diagnosis and
      open surgery is the treatment of reference.

PMID- 23171576
TI  - In situ-grown hexagonal silicon nanocrystals in silicon carbide-based films.
AB  - Silicon nanocrystals (Si-NCs) were grown in situ in carbide-based film using a
      plasma-enhanced chemical vapor deposition method. High-resolution transmission
      electron microscopy indicates that these nanocrystallites were embedded in an
      amorphous silicon carbide-based matrix. Electron diffraction pattern analyses
      revealed that the crystallites have a hexagonal-wurtzite silicon phase structure.
      The peak position of the photoluminescence can be controlled within a wavelength
      of 500 to 650 nm by adjusting the flow rate of the silane gas. We suggest that
      this phenomenon is attributed to the quantum confinement effect of hexagonal Si
      NCs in silicon carbide-based film with a change in the sizes and emission states
      of the NCs.

PMID- 23171577
TI  - Quantification of circulating CD34+/KDR+/CD45dim endothelial progenitor cells:
      analytical considerations.
AB  - The discovery of peripheral circulating cells that contribute to vasculogenesis
      and endothelial repair was one of the most fascinating breakthroughs in the
      domain of vascular research during the last two decades. The population of
      vasculogenic cells however, is heterogeneous and can be analyzed using different
      approaches including in vitro culture and flow cytometry. Circulating
      CD34(+)/KDR(+)/CD45(dim) endothelial progenitor cells (EPC) have a great
      potential as biomarkers in various cardiovascular diseases. With the expanding
      interest in this field, the development of standardized protocols is critical. In
      this review we describe in detail the pre-analytical and analytical factors that
      should be taken into account when quantifying CD34(+)/KDR(+)/CD45(dim) EPC using
      flow cytometry. Moreover, technical suggestions in order to enhance accuracy and
      reproducibility of this enumeration are provided. 

PMID- 23171579
TI  - Hepatitis E virus outbreak in monkey facility, Japan.
AB  - An outbreak of hepatitis E virus occurred in an outdoor monkey breeding facility
      in Japan during 2004-2006. Phylogenetic analysis indicated that this virus was
      genotype 3. This virus was experimentally transmitted to a cynomolgus monkey.
      Precautions should be taken by facility personnel who work with monkeys to
      prevent infection.

PMID- 23171580
TI  - Liver disease rises in England while falling elsewhere in Europe, report says.

PMID- 23171578
TI  - Emerging concepts on the anti-inflammatory actions of carbon monoxide-releasing
      molecules (CO-RMs).
AB  - Carbon monoxide-releasing molecules (CO-RMs) are a class of organometallo
      compounds capable of delivering controlled quantities of CO gas to cells and
      tissues thus exerting a broad spectrum of pharmacological effects. CO-RMs
      containing transition metal carbonyls were initially implemented to mimic the
      function of heme oxygenase-1 (HMOX1), a stress inducible defensive protein that
      degrades heme to CO and biliverdin leading to anti-oxidant and anti-inflammatory
      actions. Ten years after their discovery, the research on the chemistry and
      biological activities of CO-RMs has greatly intensified indicating that their
      potential use as CO delivering agents for the treatment of several pathological
      conditions is feasible. Although CO-RMs are a class of compounds that
      structurally diverge from traditional organic-like pharmaceuticals, their
      behaviour in the biological environments is progressively being elucidated
      revealing interesting features of metal-carbonyl chemistry towards cellular
      targets. Specifically, the presence of carbonyl groups bound to transition metals
      such as ruthenium, iron or manganese appears to make CO-RMs unique in their
      ability to transfer CO intracellularly and amplify the mechanisms of signal
      transduction mediated by CO. In addition to their well-established vasodilatory
      activities and protective effects against organ ischemic damage, CO-RMs are
      emerging for their striking anti-inflammatory properties which may be the result
      of the multiple activities of metal carbonyls in the control of redox signaling,
      oxidative stress and cellular respiration. Here, we review evidence on the
      pharmacological effects of CO-RMs in models of acute and chronic inflammation
      elaborating on some emerging concepts that may help to explain the chemical
      reactivity and mechanism(s) of action of this distinctive class of compounds in
      biological systems.

PMID- 23171581
TI  - Cancer patients need better preparation to access good quality care in a crisis.

PMID- 23171582
TI  - Test all adults aged 15 to 65 for HIV, recommends task force.

PMID- 23171583
TI  - Get basics right to improve acute kidney injury, says consensus conference.

PMID- 23171584
TI  - Pyoderma gangrenosum, acne and suppurative hidradenitis syndrome following bowel
      bypass surgery.
AB  - The clinical triad of pyoderma gangrenosum (PG), acne and suppurative
      hidradenitis (PASH) has recently been described as a new disease entity within
      the spectrum of autoinflammatory syndromes, which are an emerging group of
      inflammatory diseases distinct from autoimmune, allergic and infectious
      disorders. PASH syndrome is similar to PAPA (pyogenic arthritis, acne and PG),
      but it differs in lacking the associated arthritis and on a genetic basis. PAPA
      syndrome is caused by mutations in a gene involved in the regulation of innate
      immune responses, the PSTPIP1, while no mutations have been detected to date in
      patients with PASH syndrome. We report a young male patient who developed
      coexisting disseminated PG, typical suppurative hidradenitis and acneiform
      eruption on the face, after he had undergone bowel bypass surgery for obesity.
      The cutaneous manifestations associated with bowel bypass syndrome often mimic PG
      or other neutrophilic dermatoses, suggesting a pathogenesis related to neutrophil
      mediated inflammation for this condition. This is the first report describing
      PASH syndrome after bariatric surgery, and we propose to include such
      neutrophilic dermatoses in the list of complications occurring after bowel bypass
      surgery. Extensive genetic studies may help to clarify the etiopathogenesis of
      PASH as well as of autoinflammatory diseases in general.

PMID- 23171585
TI  - Spermatogenesis in Leptodactylus chaquensis. Histological study.
AB  - The organization and the histological characteristics of Leptodactylus chaquensis
      testis throughout the reproductive cycle were analyzed in the presented study.
      Gonads of adult males, processed with routine techniques for optical microscopy,
      revealed that during the reproductive period the seminiferous tubules were
      characterized by presentation of a large number of cysts, germ cells at the same
      maturation stage supported by Sertoli cells. All the germ line cells were also
      present in the postreproductive period and maintained their morphological
      characteristics. Primary spermatogonia were large-sized cells found isolated or
      in small groups. The rest of the cells of the germ line formed cysts. Secondary
      spermatogonia showed morphological characteristics similar to their predecessors,
      although they were smaller. Primary and secondary spermatocytes showed images of
      the different stages of the first and second meiotic division respectively. One
      finding was the presence of intercytoplasmic bridges between the secondary
      spermatocytes. Primary spermatids were rounded cells with an acrosomal vesicle
      associated with the nucleus and had cysts that were characterized by large
      intercellular spaces. Secondary spermatids were elongated cells with a well
      defined acrosome, which in the spermatozoa had the shape of an arrowhead. Another
      peculiar characteristic of this species was the fusion of the walls of the
      seminiferous tubule with the efferent duct that formed a path for spermatozoa
      during spermiation. The presence in the seminiferous tubules of all stages of the
      spermatogenic line during the two periods of the cycle studied indicated that
      Leptodactylus chaquensis had a potentially continuous reproductive cycle.

PMID- 23171586
TI  - Influence of gum tragacanth on the physicochemical and rheological properties of
      kashk.
AB  - In this study, the physicochemical properties of a low-fat dried yogurt paste
      (kashk) were determined, and the effects of different concentrations (0, 0.1, 0.3
      and 0.5% w/w) of gum tragacanth exudates from Astragalus gossypinus on the
      stability and texture of the samples were investigated by measuring amount of
      syneresis, turbidity, particle size distribution (PSD), flow behaviour and
      viscoelastic properties. The flow behaviour index was not very sensitive to the
      concentration of gum, while a remarkable concentration dependency of the power
      law consistency coefficient and Herschel-Bulkley yield stress was observed. The
      initial increase in the gum concentration at 0.1 and 0.3% levels led to a higher
      degree of syneresis, which was related to the depletion flocculation mechanism.
      However, the reduced amount of syneresis in samples containing 0.5% gum
      tragacanth was attributed to the significant increase in viscosity of the
      continuous phase, which is also accompanied by trapping of the aggregated casein
      particles. The presence of 3% salt in the samples may have led to the
      neutralization of charges on the surface of gum tragacanth; consequently, the non
      adsorbing behaviour of high-ionic-strength polysaccharides inhibited the
      formation of electrostatic protein-polysaccharide complexes. Furthermore, maximum
      values of polydispersity, syneresis and tan delta at high frequencies were found
      in samples containing 0.1% gum tragacanth.

PMID- 23171587
TI  - Probiotic potential of Lactobacillus spp. isolated from Brazilian regional ovine
      cheese.
AB  - Twelve Lactobacillus isolates from Brazilian starter-free ovine cheeses were
      evaluated for their probiotic potential. The strains were identified by 16S rDNA
      sequencing as Lactobacillus plantarum (7), Lb. brevis (2), Lb. casei (2) and Lb.
      parabuchneri (1). All strains showed variable resistance to gastric juices and
      relative tolerance to pancreatin and bile salts. Only five strains of Lb.
      plantarum could not deconjugate the sodium salt of taurodeoxycholic acid.
      Autoaggregation ability after 24 h was above 50% and hydrophobicity was higher
      than 60% for most strains. All lactobacilli could inhibit linolenic acid
      oxidation, except Lb. parabuchneri strain, whereas none of them could scavenge
      DPPH radical. beta-Galactosidase activity ranged from 47.7 to 2503 Miller units.
      Inhibition of food pathogens Listeria monocytogenes, Staphylococcus aureus,
      Bacillus cereus, Escherichia coli and Salmonella typhimurium was demonstrated and
      the production of organic acids could be associated with this effect. The
      Lactobacillus strains from Brazilian regional ovine cheese showed interesting
      functional characteristics, mainly the strains Lb. brevis SM-B and Lb. plantarum
      SM-I. Both presented high acid tolerance. In addition, Lb. brevis SM-B also
      displayed remarkable antioxidant activity and Lb. plantarum SM-I was the highest
      beta-galactosidase producer, exhibited high autoaggregation and hydrophobicity
      properties.

PMID- 23171588
TI  - Update on the Surgical Trial in Lobar Intracerebral Haemorrhage (STICH II):
      statistical analysis plan.
AB  - BACKGROUND: Previous studies had suggested that the outcome for patients with
      spontaneous lobar intracerebral haemorrhage (ICH) and no intraventricular
      haemorrhage (IVH) might be improved with early evacuation of the haematoma. The
      Surgical Trial in Lobar Intracerebral Haemorrhage (STICH II) set out to establish
      whether a policy of earlier surgical evacuation of the haematoma in selected
      patients with spontaneous lobar ICH would improve outcome compared to a policy of
      initial conservative treatment. It is an international, multi-centre, prospective
      randomised parallel group trial of early surgery in patients with spontaneous
      lobar ICH. Outcome is measured at six months via a postal questionnaire. RESULTS:
      Recruitment to the study began on 27 November 2006 and closed on 15 August 2012
      by which time 601 patients had been recruited. The protocol was published in
      Trials (http://www.trialsjournal.com/content/12/1/124/). This update presents the
      analysis plan for the study without reference to the unblinded data. The trial
      data will not be unblinded until after follow-up is completed in early 2013. The
      main trial results will be presented in spring 2013 with the aim to publish in a
      peer-reviewed journal at the same time. CONCLUSION: The data from the trial will
      provide evidence on the benefits and risks of early surgery in patients with
      lobar ICH. TRIAL REGISTRATION: ISRCTN: ISRCTN22153967.

PMID- 23171589
TI  - The treatment of imported malaria in children: an update.
AB  - Since the 2010 publication in this journal of a review of the management of
      imported malaria for U.K. children, new evidence for the treatment of both severe
      and uncomplicated malaria has been published. This review discusses these new
      data and expands the scope of the previous review to include non-endemic
      countries outside of the U.K. The results of the AQUAMAT trial in late 2010 and
      other studies have prompted the WHO to recommend that intravenous artesunate be
      used preferentially over quinine for the treatment of severe malaria caused by
      any Plasmodium species in both adults and children. Oral artemisinin-based
      combination therapies have also shown equivalent (if not better) efficacy in the
      treatment of uncomplicated malaria caused by all Plasmodium species (including
      chloroquine-resistant P vivax) in both adults and children, though there are
      issues regarding the availability of artemisinin-based combination therapies in
      many non-endemic countries. In these instances, conventional therapeutic regimens
      continue to be efficacious. Lastly, the use of primaquine for hypnozoite and
      gametocyte eradication is discussed.

PMID- 23171590
TI  - Immune response of heifers against a Staphylococcus aureus CP5 whole cell vaccine
      formulated with ISCOMATRIXTM adjuvant.
AB  - The shortcomings of Staphylococcus aureus vaccines to control bovine mastitis
      have been attributed to insufficient capacity of the vaccines to induce
      opsonizing antibodies and to stimulate cellular immune responses. Types of
      antigen, administration route and adjuvant used in a vaccine formulation have
      been identified as critical factors for the development of opsonic antibodies.
      Current commercially available vaccines for Staph. aureus bovine mastitis control
      are formulated with Al(OH)3 and oil-based adjuvants. The aim of this study was to
      evaluate the immune response of heifers immunized with a Staph. aureus CP5 whole
      cell vaccine formulated either with Al(OH)3 or ISCOMATRIXTM. Twenty primigravid
      Holstein dairy heifers in the last trimester of gestation were immunized either
      with a vaccine formulated with ISCOMATRIXTM (n = 6), Al(OH)3 (n = 7), or saline
      solution (placebo) (n = 7). Immunization was carried out 38 and 10 d before
      calving. Heifers vaccinated with Staph. aureus adjuvanted with ISCOMATRIXTM
      responded with significantly higher levels of anti-bacterin and anti-CP5 IgG and
      IgG2 in sera than animals in the Al(OH)3 or control groups. Animals in the
      ISCOMATRIXTM group responded with significantly higher anti-bacterin specific IgG
      in whey than animals in the Al(OH)3 and control groups, detected from the first
      week post calving until 60 d of lactation. Sera from animals inoculated with
      Staph. aureus in ISCOMATRIXTM, obtained 7 d post partum, significantly increased
      both the number of neutrophils ingesting bacteria and the number of bacteria
      being ingested by the neutrophils, compared with sera obtained from heifers
      vaccinated with Al(OH)3 or non-vaccinated controls. These features coupled to
      safety of the ISCOMATRIXTM formulation, warrant additional studies.

PMID- 23171591
TI  - Migratory birds, ticks, and crimean-congo hemorrhagic fever virus.

PMID- 23171592
TI  - Genomic signatures characterize leukocyte infiltration in myositis muscles.
AB  - BACKGROUND: Leukocyte infiltration plays an important role in the pathogenesis
      and progression of myositis, and is highly associated with disease severity.
      Currently, there is a lack of: efficacious therapies for myositis; understanding
      of the molecular features important for disease pathogenesis; and potential
      molecular biomarkers for characterizing inflammatory myopathies to aid in
      clinical development. METHODS: In this study, we developed a simple model and
      predicted that 1) leukocyte-specific transcripts (including both protein-coding
      transcripts and microRNAs) should be coherently overexpressed in myositis muscle
      and 2) the level of over-expression of these transcripts should be correlated
      with leukocyte infiltration. We applied this model to assess immune cell
      infiltration in myositis by examining mRNA and microRNA (miRNA) expression
      profiles in muscle biopsies from 31 myositis patients and 5 normal controls.
      RESULTS: Several gene signatures, including a leukocyte index, type 1 interferon
      (IFN), MHC class I, and immunoglobulin signature, were developed to characterize
      myositis patients at the molecular level. The leukocyte index, consisting of
      genes predominantly associated with immune function, displayed strong concordance
      with pathological assessment of immune cell infiltration. This leukocyte index
      was subsequently utilized to differentiate transcriptional changes due to
      leukocyte infiltration from other alterations in myositis muscle. Results from
      this differentiation revealed biologically relevant differences in the
      relationship between the type 1 IFN pathway, miR-146a, and leukocyte infiltration
      within various myositis subtypes. CONCLUSIONS: Results indicate that a likely
      interaction between miR-146a expression and the type 1 IFN pathway is confounded
      by the level of leukocyte infiltration into muscle tissue. Although the role of
      miR-146a in myositis remains uncertain, our results highlight the potential
      benefit of deconvoluting the source of transcriptional changes in myositis muscle
      or other heterogeneous tissue samples. Taken together, the leukocyte index and
      other gene signatures developed in this study may be potential molecular
      biomarkers to help to further characterize inflammatory myopathies and aid in
      clinical development. These hypotheses need to be confirmed in separate and
      sufficiently powered clinical trials.

PMID- 23171593
TI  - Epiblast cell number and primary embryonic stem cell colony generation are
      increased by culture of cleavage stage embryos in insulin.
AB  - Human embryos for hESC derivation are often donated at the cleavage stage and of
      reduced quality. Poor quality embryos have lower efficiency for hESC derivation.
      However, cleavage stage mouse embryos develop into higher quality expanded
      blastocysts if they are cultured with insulin, suggesting that this approach
      could be used to improve hESC derivation from poor quality cleavage stage
      embryos. The present study used a mouse model to examine this approach. In
      particular we examined the effect of insulin on the number of epiblast cells in
      blastocysts on days 4, 5 and 6 using Oct4 and Nanog co-expression. Second we
      examined the effect of insulin on the frequency with which outgrowths can be
      derived from these. Finally, we tested whether prior culture in the presence of
      insulin results in blastocysts with increased capacity to generate ESC colonies.
      Culture of cleavage stage embryos with insulin increased the number of Oct4 and
      Nanog positive cells in blastocysts at all time points examined. Prior culture
      with insulin had no effect on outgrowths generated from blastocysts plated on
      days 4 or 5. However, insulin treatment of blastocysts plated on day 6 resulted
      in increased numbers of outgrowths with larger epiblasts compared with controls.
      13% of insulin treated day 6 blastocysts produced primary ESC colonies compared
      with 6% of controls. In conclusion, treatment with insulin can improve epiblast
      cell number in mice leading to an increase with which primary ESC colonies can be
      generated and may improve hESC isolation from reduced quality embryos donated at
      the cleavage stage.

PMID- 23171594
TI  - Early identification and control of carbapenemase-producing Klebsiella
      pneumoniae, originating from contaminated endoscopic equipment.
AB  - Klebsiella producing carbapenemase is an emerging pathogen. We report
      transmission of this organism by contaminated endoscopic instruments. Quick
      identification of source, staff education, contact precautions, and emphasis on
      hand and environmental hygiene led to case control and prevention of outbreak.

PMID- 23171595
TI  - Micronutrients in age-related macular degeneration.
AB  - Several lines of evidence from in vitro and in vivo studies suggest that specific
      micronutrients may have beneficial effects in age-related macular degeneration
      (AMD). Such effects appear to be complex and may include filtering short
      wavelength light and attenuating oxidative and inflammatory damage as well as
      other structural and physiological factors. There is clinical evidence for
      potential benefits from vitamin C, beta-carotene, vitamin E and zinc, as well as
      emerging epidemiological and clinical data for the carotenoids lutein and
      zeaxanthin and for omega-3 fatty acids. A survey of the literature suggests that
      some specific micronutrients may be of value in treating or preventing AMD, but
      further prospective studies are needed to further identify and characterize their
      effects and place in therapy.

PMID- 23171597
TI  - The oxidized low-density lipoprotein/beta2-glycoprotein I complex is associated
      with abdominal obesity in healthy middle-aged men.
AB  - BACKGROUND/AIMS: Oxidized low-density lipoprotein (oxLDL) in complex with beta2
      glycoprotein I (beta2GPI) has been associated with autoimmune diseases, diabetes
      mellitus, chronic renal disease and coronary atherosclerosis. The aim of our
      study was to determine whether plasma levels of oxLDL/beta2GPI complexes are
      associated with insulin resistance, inflammation and markers of endothelial
      damage in obese middle-aged men and, if so, whether oxLDL/beta2GPI correlates
      better with insulin resistance parameters than oxLDL, advanced oxidation protein
      products (AOPP) or thioredoxin. METHODS: A total of 72 healthy men were recruited
      (41 obese and 31 nonobese individuals). Waist circumference >94 cm was used as
      the criterion for abdominal obesity. RESULTS: The obese men demonstrated higher
      oxLDL/beta2GPI levels (p < 0.001), homeostasis model assessment of insulin
      resistance (p < 0.01) and intima-media thickness of the common carotid artery (p
      < 0.01). oxLDL/beta2GPI correlated with more insulin resistance parameters
      compared to AOPP, thioredoxin or oxLDL. Furthermore, oxLDL/beta2GPI was
      associated with plasminogen activator inhibitor-I (PAI-I; r = 0.365, p < 0.001)
      and negatively with interleukin-8 (r = -0.297, p < 0.05). CONCLUSIONS: In
      summary, oxLDL/beta2GPI reflects the criterion for abdominal obesity and markers
      of insulin resistance in our study. The independent positive correlation with PAI
      I indicates that oxLDL/beta2GPI may serve as an early marker of low-grade
      inflammation and atherosclerosis initiation.

PMID- 23171598
TI  - Group 2 vaccinia virus, Brazil.
AB  - In 2011, vaccinia virus caused an outbreak of bovine vaccinia, affecting dairy
      cattle and dairy workers in Brazil. Genetic and phenotypic analyses identified
      this isolate as distinct from others recently identified, thereby reinforcing the
      hypothesis that different vaccinia virus strains co-circulate in Brazil.

PMID- 23171599
TI  - Synthesis and characterization of titanium complex with a dithiolate ligand for
      green LCD color filter dyes.
AB  - Three green compounds for color filter dyes based on bis(cyclopentadienyl)
      titanium complexes including dithiolate ligand were synthesized. Physical
      properties by the change of the substitution groups of the synthesized materials
      were systematically examined. UV-visible absorption spectrum of the synthesized
      materials showed maximum absorbing wavelengths of 427 to 430 nm and 632 to 635 nm
      in solution state, and 434 to 438 nm and 637 to 651 nm in film state, indicating
      green and black colors. It was observed that the extinction coefficient values
      (log epsilon) of all the synthesized materials are very high at 4.0 or above. In
      addition, it was shown that since the Td values of three synthesized materials
      show thermal stability higher than 240 degrees C, they possess high potential to
      be applied as dyes for LCD color filter and black matrix addictive.

PMID- 23171600
TI  - Analysis of complete Puumala virus genome, Finland.
AB  - Puumala virus causes nephropathia epidemica, a rodent-borne zoonosis that is
      endemic to Europe. We sequenced the complete Puumala virus genome that was
      directly recovered from a person who died and compared it with those of viruses
      from local bank voles. The virus strain involved was neither a unique nor rare
      genetic variant.

PMID- 23171602
TI  - The ENT emergency clinic: does senior input matter?
AB  - BACKGROUND: Many ENT conditions can be treated in the emergency clinic on an
      ambulatory basis. Our clinic traditionally had been run by foundation year two
      and specialty trainee doctors (period one). However, with perceived increasing
      inexperience, a dedicated registrar was assigned to support the clinic (period
      two). This study compared admission and discharge rates for periods one and two
      to assess if greater registrar input affected discharge rate; an increase in
      discharge rate was used as a surrogate marker of efficiency. METHOD: Data was
      collected prospectively for patients seen in the ENT emergency clinic between 1
      August 2009 and 31 July 2011. Time period one included data from patients seen
      between 1 August 2009 and 31 July 2010, and time period two included data
      collected between 1 August 2010 and 31 July 2011. RESULTS: The introduction of
      greater registrar support increased the number of patients that were discharged,
      and led to a reduction in the number of children requiring the operating theatre.
      CONCLUSION: The findings, which were determined using clinic outcomes as markers
      of the quality of care, highlighted the benefits of increasing senior input
      within the ENT emergency clinic.

PMID- 23171601
TI  - The effects of reducing worry in patients with persecutory delusions: study
      protocol for a randomized controlled trial.
AB  - BACKGROUND: Our approach to advancing the treatment of psychosis is to focus on
      key single symptoms and develop interventions that target the mechanisms that
      maintain them. In our theoretical research we have found worry to be an important
      factor in the development and maintenance of persecutory delusions. Worry brings
      implausible ideas to mind, keeps them there, and makes the experience
      distressing. Therefore the aim of the trial is to test the clinical efficacy of a
      cognitive-behavioral intervention for worry for patients with persecutory
      delusions and determine how the worry treatment might reduce delusions.
      METHODS/DESIGN: An explanatory randomized controlled trial--called the Worry
      Intervention Trial (WIT)--with 150 patients with persecutory delusions will be
      carried out. Patients will be randomized to the worry intervention in addition to
      standard care or to standard care. Randomization will be carried out
      independently, assessments carried out single-blind, and therapy competence and
      adherence monitored. The study population will be individuals with persecutory
      delusions and worry in the context of a schizophrenia spectrum diagnosis. They
      will not have responded adequately to previous treatment. The intervention is a
      six-session cognitive-behavioral treatment provided over eight weeks. The control
      condition will be treatment as usual, which is typically antipsychotic medication
      and regular appointments. The principal hypotheses are that a worry intervention
      will reduce levels of worry and that it will also reduce the persecutory
      delusions. Assessments will be carried out at 0 weeks (baseline), 8 weeks (post
      treatment) and 24 weeks (follow-up). The statistical analysis strategy will
      follow the intention-to-treat principle and involve the use of linear mixed
      models to evaluate and estimate the relevant between- and within-subjects effects
      (allowing for the possibility of missing data). Both traditional regression and
      newer instrumental variables analyses will examine mediation. The trial is funded
      by the UK Medical Research Council (MRC)/NHS National Institute of Health
      Research (NIHR) Efficacy and Mechanism Evaluation (EME) Programme. DISCUSSION:
      This will be the first large randomized controlled trial specifically focused
      upon persecutory delusions. The project will produce a brief, easily administered
      intervention that can be readily used in mental health services. TRIAL
      REGISTRATION: Current Controlled Trials ISRCTN23197625.

PMID- 23171604
TI  - Effect of dibutyryl cyclic adenosine monophosphate on reactive oxygen species and
      glutathione of porcine oocytes, apoptosis of cumulus cells, and embryonic
      development.
AB  - The present study was conducted to investigate the effect of dibutyryl cyclic
      adenosine monophosphate (dbcAMP) supplemented into porcine maturation medium on
      reactive oxygen species (ROS) and glutathione (GSH) levels of oocytes, and
      apoptosis of cumulus cells (CC). In addition, the effect of dbcAMP on embryonic
      development following in vitro fertilization (IVF) or parthenogenetic activation
      (PA) was determined. Cumulus-oocyte complexes (COCs) were cultured in 0 mM
      (control), 0.5 mM, 1 mM, 5 mM, or 10 mM dbcAMP-supplemented medium for 22 h, then
      for another 22 h without dbcAMP. GSH and ROS levels of oocytes were assessed at
      44 h of culture by dichlorohydrofluorescein diacetate or 4-chloromethyl-6,8
      difluoro-7-hydroxycoumarin staining, respectively. Additionally, COCs were
      cultured in 0.5 mM or 1 mM dbcAMP and then fertilized in vitro or activated
      parthenogenetically. Embryonic development and blastocyst cell numbers and
      apoptosis levels on day 8 of culture were investigated. CC apoptosis at 44 h of
      culture and blastocyst apoptosis were assessed by terminal deoxynucleotidyl
      transferase dUTP nick end labeling (TUNEL) assay. GSH levels in the 0.5 mM dbcAMP
      and control groups were increased (P < 0.05), while levels of oocyte ROS and CC
      apoptosis in the control, 0.5 mM, and 1 mM dbcAMP groups were significantly lower
      than the levels in other groups. Cleavage and blastocyst rates, cell numbers, and
      apoptosis levels were not significantly different in embryos derived by either
      IVF or PA among the groups, with the exception of significantly increased
      apoptotic levels in IVF blastocysts produced from oocytes treated with 1 mM
      dbcAMP. In conclusion, dbcAMP treatment during in vitro maturation (IVM) did not
      improve embryonic development under our study's parameters compared with control
      conditions, although 0.5 mM dbcAMP showed significantly higher GSH levels and
      lower blastocyst apoptotic levels compared with 1 mM dbcAMP.

PMID- 23171603
TI  - Body mass index and dental caries in children and adolescents: a systematic
      review of literature published 2004 to 2011.
AB  - THE OBJECTIVE: The authors undertook an updated systematic review of the
      relationship between body mass index and dental caries in children and
      adolescents. METHOD: The authors searched Medline, ISI, Cochrane, Scopus, Global
      Health and CINAHL databases and conducted lateral searches from reference lists
      for papers published from 2004 to 2011, inclusive. All empirical papers that
      tested associations between body mass index and dental caries in child and
      adolescent populations (aged 0 to 18 years) were included. RESULTS: Dental caries
      is associated with both high and low body mass index. CONCLUSION: A non-linear
      association between body mass index and dental caries may account for
      inconsistent findings in previous research. We recommend future research
      investigate the nature of the association between body mass index and dental
      caries in samples that include a full range of body mass index scores, and
      explore how factors such as socioeconomic status mediate the association between
      body mass index and dental caries.

PMID- 23171605
TI  - Potential of castor bean (Ricinus communis L.) for phytoremediation of mine
      tailings and oil production.
AB  - Bioenergy production combined with phytoremediation has been suggested to help in
      solving two critical world problems: the gradual reduction of fossil fuels and
      soil contamination. The aim of this research was to investigate the potential for
      the use of Ricinus communis L. (castor oil plant) as an energy crop and plant
      species to remediate metal-polluted sites. This study was performed in mine
      tailings containing high concentrations of Cu, Zn, Mn, Pb and Cd. Physico
      chemical characterization, total, DTPA-extractable and water-soluble metals in
      rhizospheric tailings heap samples were carried. Metal concentrations in plant
      tissues and translocation factors (TFs) were also determined. The Ricinus seed
      oil content was high between 41 and 64%, seeds from San Francisco site 6 had the
      highest oil content, while these from site 7 had the lowest. No trend between oil
      yield vs seed origin site was observed. Seed-oil content was negatively
      correlated with root concentration of Cu, Zn, Pb and Cd, but no correlation was
      observed with the extractable-metals. According to its shoot metal concentrations
      and TFs, castor bean is not a metal accumulator plant. This primary colonizing
      plant is well suited to cope with the local toxic conditions and can be useful
      for the stabilization of these residues, and for then decreasing metal
      bioavailability, dispersion and human health risks on these barren tailings heaps
      and in the surrounding area. Our work is the first report regarding combined oil
      production and a phytostabilization role for Ricinus plants in metal mine
      tailings and may give a new value to suitable metal-polluted areas.

PMID- 23171606
TI  - A framework for identifying carbon hotspots and forest management drivers.
AB  - Spatial analyses of ecosystem system services that are directly relevant to both
      forest management decision making and conservation in the subtropics are rare.
      Also, frameworks that identify and map carbon stocks and corresponding forest
      management drivers using available regional, national, and international-level
      forest inventory datasets could provide insights into key forest structural
      characteristics and management practices that are optimal for carbon storage. To
      address this need we used publicly available USDA Forest Service Forest Inventory
      and Analysis data and spatial analyses to develop a framework for mapping "carbon
      hotspots" (i.e. areas of significantly high tree and understory aboveground
      carbon stocks) across a range of forest types using the state of Florida, USA as
      an example. We also analyzed influential forest management variables (e.g. forest
      types, fire, hurricanes, tenure, management activities) using generalized linear
      mixed modeling to identify drivers associated with these hotspots. Most of the
      hotspots were located in the northern third of the state some in peri-urban
      areas, and there were no identifiable hotspots in South Florida. Forest
      silvicultural treatments (e.g. site preparation, thinning, logging, etc) were not
      significant predictors of hotspots. Forest types, site quality, and stand age
      were however significant predictors. Higher site quality and stand age increased
      the probability of forests being classified as a hotspot. Disturbance type and
      time since disturbance were not significant predictors in our analyses. This
      framework can use globally available forest inventory datasets to analyze and map
      ecosystems service provision areas and bioenergy supplies and identify forest
      management practices that optimize these services in forests.

PMID- 23171607
TI  - An analysis of the content and clinical implications of online advertisements for
      female genital cosmetic surgery.
AB  - OBJECTIVES: Women who are contemplating any form of female genital cosmetic
      surgery (FGCS) are likely to seek information from provider websites. The aim of
      this study is to examine the breadth, depth and quality of clinical information
      communicated to women on 10 popular sites and to discuss the implications of the
      results. METHODS: The content of online advertisement from 10 private providers
      that offer FGCS procedures was examined according to 16 information categories
      relating to indications for surgery, types of procedure, risks and benefits.
      RESULTS: FGCS procedures were presented on all of the provider websites as an
      effective treatment for genital appearance concerns. No explanation for
      presenting clinical complaints was found. There was scanty reference to
      appearance diversity. Only minimal scientific information on outcomes or risks
      could be identified. There was no mention of potential alternative ways for
      managing appearance concerns or body dissatisfaction. CONCLUSIONS: The quality
      and quantity of clinical information in FGCS provider sites is poor, with
      erroneous information in some instances. Impeccable professionalism and ethical
      integrity is crucial for this controversial practice. Clear and detailed
      guidelines on how to raise the standard of information to women on all aspects of
      FGCS are urgently needed.

PMID- 23171608
TI  - Changes in plasma progesterone levels in the caudal vena cava and the jugular
      vein and luteinizing hormone secretion pattern after feeding in lactating and non
      lactating dairy cows.
AB  - The present study was designed to assess progesterone profiles at the secreted
      (caudal vena cava) and circulating levels (jugular vein) and luteinizing hormone
      (LH) secretion pattern in lactating and non-lactating cows with reference to
      feeding. Four lactating and four non-lactating cycling Holstein cows were
      examined. Blood samples were collected simultaneously from the caudal vena cava
      (via a catheter inserted from the coccygeal vein) and the jugular vein every 15
      min for 12 h (0500-1700 h) during the functional luteal phase. Cows were fed 50%
      of the daily diet 6 h after the start of blood sampling. During the 12-h sampling
      period, mean progesterone concentrations in the caudal vena cava did not differ
      between lactating and non-lactating cows (49.0 +/- 2.9 and 53.3 +/- 3.7 ng/ml;
      mean +/- SE), whereas mean progesterone concentrations in the jugular vein in
      lactating cows were higher than those in non-lactating cows (6.4 +/- 0.1 and 5.6
      +/- 0.1 ng/ml, P < 0.001). Lactating cows had a higher frequency of LH pulses
      than non-lactating cows (7.0 +/- 0.7 and 4.3 +/- 0.9 pulses/12 h, P<0.05). The
      influence of feeding was not observed on LH profiles but was observed on
      progesterone profiles in both veins. Progesterone concentrations in the caudal
      vena cava increased after feeding in both groups. Progesterone concentrations in
      the jugular vein decreased after feeding in lactating cows but not in non
      lactating cows. These results indicate the difference in feeding-related changes
      in progesterone dynamics between lactating and non-lactating cows.

PMID- 23171609
TI  - Exposure to estrogen mimicking the level of late pregnancy suppresses estrus
      subsequently induced by estrogen at the level of the follicular phase in
      ovariectomized shiba goats.
AB  - A high-estrogen environment during late pregnancy is suspected to cause
      postpartum silent ovulation, and progesterone (P4) is suggested to recover
      estrus. However, few attempts have been undertaken to elucidate the influence of
      these steroids on estrus by analyzing hormonal profiles. We investigated estrus
      and luteinizing hormone (LH) surges in ovariectomized goats (n=6) assigned to
      three treatments in a cross-over design. In groups 1 and 2, 200 MUg/kg body
      weight/day estradiol benzoate (Dose-200 E2B) was administered for 14 days
      concurrent with P4 for 11 days, while in the control, saline solution and P4 were
      administered likewise. Ten days after the final administration of Dose-200 E2B,
      group 2 was treated with P4 for 8 days, and all groups were treated with 2 MUg/kg
      body weight E2B (Dose-2 E2B) 20 days after the final administration of Dose-200
      E2B (or saline solution). The proportion of cases expressing estrus after the
      administration of Dose-2 E2B was smaller (P<0.01) in group 1 than in the control
      (1/6, 3/6 and 6/6; groups 1 and 2 and the control, respectively). The proportions
      of cases generating LH surges did not differ (P>0.1) among the groups (5/6, 5/6
      and 6/6; groups 1 and 2 and the control, respectively), but the peak
      concentrations in groups 1 and 2 (26.2 +/- 14.7 and 11.3 +/- 6.7 ng/ml) were
      lower (P<0.01) than those in the control (67.8 +/- 19.4 ng/ml). These results
      demonstrated that elevation of plasma estrogen mimicking late pregnancy inhibits
      the subsequent estrus induced by estrogen simulating the follicular phase.

PMID- 23171610
TI  - Cardiorespiratory fitness level correlates inversely with excess post-exercise
      oxygen consumption after aerobic-type interval training.
AB  - BACKGROUND: The purpose of this study was to reveal any association between
      cardiorespiratory fitness level and excess post-exercise oxygen consumption
      (EPOC) using three cycling protocols with varying degrees of exercise intensity,
      i.e., sprint interval training (SIT), high-intensity interval aerobic training
      (HIAT), and continuous aerobic training (CAT). FINDINGS: Ten healthy men, aged 20
      to 31 years, attended a cross-over experiment and completed three exercise
      sessions: SIT consisting of 7 sets of 30-s cycling at 120% VO2max with a 15-s
      rest between sets; HIAT consisting of 3 sets of 3-min cycling at 80~90% VO2max
      with a 2-min active rest at 50% VO2max between sets; and CAT consisting of 40 min
      of cycling at 60~65% VO2max. During each session, resting VO2, exercise VO2, and
      a 180-min post-exercise VO2 were measured. The net exercise VO2 during the SIT,
      HIAT, and CAT averaged 14.7 +/- 1.5, 31.8 +/- 4.1, and 71.1 +/- 10.0 L, and the
      EPOCs averaged 6.8 +/- 4.0, 4.5 +/- 3.3, and 2.9 +/- 2.8 L, respectively. The
      EPOC with SIT was greater than with CAT (P < 0.01) and HIAT (P = 0.12).
      Correlation coefficients obtained between subjects' VO2max and the ratio of EPOC
      to net exercise VO2 for SIT, HIAT, and CAT were -0.61 (P = 0.06), -0.79 (P <
      0.01), and -0.42 (P = 0.23), respectively. CONCLUSIONS: Our data suggest that
      cardiorespiratory fitness level correlates negatively with the magnitude of EPOC,
      especially when performing aerobic-type interval training.

PMID- 23171611
TI  - Intraoperative retinal break formation in 23-/25-gauge vitrectomy versus 20-gauge
      vitrectomy.
AB  - BACKGROUND: This study was undertaken to examine the possible effect of
      microcannula-guided entry sites on the rate of intraoperative retinal break
      formation. METHODS: In this historical cohort study, all patients having
      undergone vitrectomy with epiretinal or internal limiting membrane peeling
      performed by one surgeon between January 2005 and March 2009 were included. All
      procedures with microcannula-guided entry sites (23- and 25-gauge vitrectomy)
      were compared to procedures without the use of microcannulas (20-gauge
      vitrectomy). RESULTS: A total of 221 eyes with a follow-up of at least 30 days
      were analyzed. The total incidence of intraoperative retinal break formation was
      25.2% (n = 28/111) for the 20-gauge group and 12.7% (n = 14/110) for the 23-/25
      gauge group, resulting in an odds ratio of 2.313 (95% confidence interval 1.142
      4.685) of an increased rate in the 20-gauge group. CONCLUSION: This study
      demonstrates that intraoperative retinal breaks during vitrectomy are reduced in
      the microcannula-guided techniques compared to 20-gauge vitrectomy. This effect
      may be attributed to the protection of the vitreous base during surgery. Further
      prospective studies are warranted.

PMID- 23171612
TI  - Alcohol-induced changes in cerebral blood flow and cerebral blood volume in
      social drinkers.
AB  - AIMS: Although it is known that alcohol has vasoactive properties, previous
      studies have not investigated the relationship between cerebral blood flow (CBF)
      and cerebral blood volume (CBV) after alcohol consumption. The aim of this study
      was to investigate effects of alcohol on CBF and CBV, both globally and
      regionally, in social drinkers. METHODS: The method of choice was dynamic
      susceptibility contrast magnetic resonance imaging (DSC-MRI). Eight males were
      scanned twice on two separate days; once after consumption of alcohol (blood
      alcohol concentration (BAC) of 0.08%) and once sober. RESULTS: The results showed
      an average increase of CBF after alcohol consumption, both in grey matter (GM)
      and in white matter (WM), with a CBF(BAC of 0.08%)/CBF(baseline) ratio of 1.2.
      Regional increases in CBF were seen in areas close to where the large brain
      feeding blood vessels enter the brain, in the thalamus region and in the frontal
      brain regions. The lowest CBF changes were seen in the occipital brain regions.
      There was also an increase in CBV after alcohol consumption, in particular across
      WM regions. CONCLUSION: In conclusion, a BAC of 0.08% causes both an average
      increase in global and regional CBF. There was stronger correlation between
      alcohol-induced changes in CBF and CBV in WM than in GM, suggesting the
      vasculature in the WM to be relatively more affected than the GM. Simultaneous
      measurements of CBF and CBV after acute alcohol intoxication in social drinkers
      are important in basic human neuroscience research to elucidate and understand
      brain physiology in the presence of exogenous neuro-pharmaceutical manipulations.

PMID- 23171613
TI  - Per-capita alcohol consumption and all-cause male mortality in Australia, 1911
      2006.
AB  - AIMS: Given the variety of relationships found between alcohol consumption and
      health using individual data (both negative and positive), the likely impact of
      changes in population-level alcohol consumption on health at the population level
      is not clear. This paper uses historical data from 1911 to 2006 to assess the
      relationship between changes in per-capita alcohol consumption on total male
      mortality in Australia. METHODS: A longitudinal aggregate study using Australian
      per-capita alcohol consumption and mortality data from 1911 to 2006. Analysis is
      undertaken using autoregressive integrated moving average time-series methods.
      RESULTS: Per-capita pure alcohol consumption has a significant association with
      male all-cause mortality, with an increase (decrease) of 1 l per-capita per year
      associated with a 1.5% increase (decrease) in male mortality (controlling for
      female mortality and smoking rates). The association between per-capita
      consumption and mortality was significant for all age groups, with a particularly
      strong effect among 15-29 year olds. CONCLUSION: These results place Australia in
      the group of countries for which a positive association between per-capita
      alcohol consumption and total mortality can be demonstrated. Thus, despite the
      beneficial effects of alcohol consumption on health found in many studies,
      increases in consumption at the population level in Australia are associated with
      declines in population health. Thus, per-capita alcohol consumption in Australia
      is a significant contributor to rates of male mortality, particularly among young
      adults, suggesting an interaction between per-capita consumption and risky
      episodic drinking. The policies aiming to reduce population-level alcohol
      consumption and episodic risky drinking have the potential to substantially
      improve population-health outcomes in Australia, particularly among young men.

PMID- 23171614
TI  - Detecting emotion in others: increased insula and decreased medial prefrontal
      cortex activation during emotion processing in elite adventure racers.
AB  - Understanding the neural processes that characterize elite performers is a first
      step to develop a neuroscience model that can be used to improve performance in
      stressful circumstances. Adventure racers are elite athletes that operate in
      small teams in the context of environmental and physical extremes. In particular,
      awareness of team member's emotional status is critical to the team's ability to
      navigate high-magnitude stressors. Thus, this functional magnetic resonance
      imaging (fMRI) study examined the hypothesis that adventure racers would show
      altered emotion processing in brain areas that are important for resilience and
      social awareness. Elite adventure racers (n = 10) were compared with healthy
      volunteers (n = 12) while performing a simple emotion face-processing (modified
      Hariri) task during fMRI. Across three types of emotional faces, adventure racers
      showed greater activation in right insula, left amygdala and dorsal anterior
      cingulate. Additionally, compared with healthy controls adventure racers showed
      attenuated right medial prefrontal cortex activation. These results are
      consistent with previous studies showing elite performers differentially activate
      neural substrates underlying interoception. Thus, adventure racers differentially
      deploy brain resources in an effort to recognize and process the internal
      sensations associated with emotions in others, which could be advantageous for
      team-based performance under stress. 

PMID- 23171615
TI  - The neuropsychology of disgust.

PMID- 23171616
TI  - Aberrant neurocognitive processing of fear in young girls with Turner syndrome.
AB  - Appraisal of fearful stimuli is an integral aspect of social cognition. Neural
      circuitry underlying this phenomenon has been well-described and encompasses a
      distributed network of affective and cognitive nodes. Interestingly, this ability
      to process fearful faces is impaired in Turner syndrome (TS), a genetic disorder
      of females in which all or part of an X chromosome is missing. However,
      neurofunctional correlates for this impairment have not been well-studied,
      particularly in young girls. Given that the core features of TS include X
      chromosome gene haploinsufficiency and secondary sex hormone deficiencies,
      investigation of fearful face processing may provide insights into the influence
      of X chromosome gene expression on this network. Therefore, we examined
      behavioral and neural responses during an explicit emotional face labeling task
      in 14 prepubertal girls with TS and 16 typically developing age-matched controls
      (6-13 years). We demonstrate that girls with TS have a specific impairment in the
      identification of fearful faces and show decreased activation in several
      cognitive control regions, including the anterior dorsal anterior cingulate
      cortex, dorsolateral prefrontal cortex and posterior cingulate gyrus. Our results
      indicate that aberrant functional activation in dorsal cognitive regions plays an
      integral role in appraisal of, and regulation of response to fear in TS. 

PMID- 23171617
TI  - Reversible inactivation of pSTS suppresses social gaze following in the macaque
      (Macaca mulatta).
AB  - Humans and other primates shift their attention to follow the gaze of others
      [gaze following (GF)]. This behavior is a foundational component of joint
      attention, which is severely disrupted in neurodevelopmental disorders such as
      autism and schizophrenia. Both cortical and subcortical pathways have been
      implicated in GF, but their contributions remain largely untested. While the
      proposed subcortical pathway hinges crucially on the amygdala, the cortical
      pathway is thought to require perceptual processing by a region in the posterior
      superior temporal sulcus (pSTS). To determine whether pSTS is necessary for
      typical GF behavior, we engaged rhesus macaques in a reward discrimination task
      confounded by leftward- and rightward-facing social distractors following saline
      or muscimol injections into left pSTS. We found that reversible inactivation of
      left pSTS with muscimol strongly suppressed GF, as assessed by reduced influence
      of observed gaze on target choices and saccadic reaction times. These findings
      demonstrate that activity in pSTS is required for normal GF by primates. 

PMID- 23171619
TI  - Porcine reproductive and respiratory syndrome virus, Thailand, 2010-2011.
AB  - Characterization of porcine reproductive and respiratory syndrome virus (PRRSV)
      isolates from pigs in Thailand showed 30-aa discontinuous deletions in
      nonstructural protein 2, identical to sequences for highly pathogenic PRRSV. The
      novel virus is genetically related to PRRSV from China and may have spread to
      Thailand through illegal transport of infectious animals from bordering
      countries.

PMID- 23171618
TI  - Distributed neural system for emotional intelligence revealed by lesion mapping.
AB  - Cognitive neuroscience has made considerable progress in understanding the neural
      architecture of human intelligence, identifying a broadly distributed network of
      frontal and parietal regions that support goal-directed, intelligent behavior.
      However, the contributions of this network to social and emotional aspects of
      intellectual function remain to be well characterized. Here we investigated the
      neural basis of emotional intelligence in 152 patients with focal brain injuries
      using voxel-based lesion-symptom mapping. Latent variable modeling was applied to
      obtain measures of emotional intelligence, general intelligence and personality
      from the Mayer, Salovey, Caruso Emotional Intelligence Test (MSCEIT), the
      Wechsler Adult Intelligence Scale and the Neuroticism-Extroversion-Openness
      Inventory, respectively. Regression analyses revealed that latent scores for
      measures of general intelligence and personality reliably predicted latent scores
      for emotional intelligence. Lesion mapping results further indicated that these
      convergent processes depend on a shared network of frontal, temporal and parietal
      brain regions. The results support an integrative framework for understanding the
      architecture of executive, social and emotional processes and make specific
      recommendations for the interpretation and application of the MSCEIT to the study
      of emotional intelligence in health and disease. 

PMID- 23171620
TI  - Efficacy of clarithromycin on biofilm formation  of methicillin-resistant
      Staphylococcus pseudintermedius.
AB  - BACKGROUND: Surgical site infections (SSIs) caused by biofilm-forming methicillin
      resistant Staphylococcus pseudintermedius (MRSP) have emerged as the most common
      hospital-acquired infections in companion animals. No methods currently exist for
      the therapeutic remediation of SSIs caused by MRSP in biofilms. Clarithromycin
      (CLA) has been shown to prevent biofilm formation by Staphylococcus aureus. This
      study aims to assess the in vitro activity of CLA in eradicating MRSP biofilm
      formation on various materials. RESULTS: Quantitative assay results (P = 0.5126)
      suggest that CLA does not eradicate MRSP biofilm formation on polystyrene after 4
      - 24 h growth periods. Scanning electron micrographs confirmed that CLA did not
      eradicate MRSP biofilm formed on orthopaedic implants. CONCLUSIONS: By
      determining the in vitro characteristics and activities of MRSP isolates alone
      and against antibiotics, in vitro models of biofilm related infections can be
      made. In vitro data suggests that CLA does not effectively eradicate S.
      pseudintermedius biofilms in therapeutic doses.

PMID- 23171621
TI  - Transmission routes for nipah virus from Malaysia and Bangladesh.
AB  - Human infections with Nipah virus in Malaysia and Bangladesh are associated with
      markedly different patterns of transmission and pathogenicity. To compare the 2
      strains, we conducted an in vivo study in which 2 groups of ferrets were
      oronasally exposed to either the Malaysia or Bangladesh strain of Nipah virus.
      Viral shedding and tissue tropism were compared between the 2 groups. Over the
      course of infection, significantly higher levels of viral RNA were recovered from
      oral secretions of ferrets infected with the Bangladesh strain. Higher levels of
      oral shedding of the Bangladesh strain of Nipah virus might be a key factor in
      onward transmission in outbreaks among humans.

PMID- 23171622
TI  - Development of a multifunctional detoxifying unit for liver failure patients.
AB  - BACKGROUND/AIMS: Extracorporeal blood detoxification strategies aimed at
      supporting impaired liver function have been explored because of the imbalance
      between donor organs and waiting patients. A limited number of artificial devices
      are now available clinically, and these are characterized by the use of
      multistage adsorption procedures in conjunction with hemodialysis, but these
      features simultaneously increase system complexity and treatment costs. METHODS:
      The authors developed a simpler strategy for liver dialysis based on the use of a
      multifunctional filter, which enables plasma separation and perfusion in a single
      unit. RESULTS: Liver dialysis treatments were successfully performed using the
      devised unit when bovine blood containing uremic and hepatic toxins was
      circulated. Removal of the solutes under investigation was significant, and
      reduction ratios of 78% for urea, 98% for creatinine and 91% for bilirubin were
      achieved. Plasma free hemoglobin levels were reasonably maintained despite
      prolonged blood recirculation for 5 h, and platelet, hematocrit and hemoglobin
      levels remained uniform throughout liver dialysis sessions. CONCLUSION: The
      devised liver support unit may offer a straightforward and efficient means of
      cleansing blood for patients with hepatic failure.

PMID- 23171623
TI  - Neonatal airway lesions: our experience and a review of the literature.
AB  - OBJECTIVES: This paper reports on two rare cases of neonatal airway lesions with
      differing aetiology that were successfully managed by surgery, and provides a
      review of the literature on neonatal stridor and airway lesions. CASE REPORTS: In
      the first case report, a newborn presented with a nasopharyngeal teratoma. In the
      second case report, a newborn presented with a congenital laryngeal saccular
      cyst. Difficulties in the diagnosis of these lesions, and surgical and
      anaesthetic challenges in their management are discussed. CONCLUSION: Every case
      of neonatal airway distress must be evaluated and the cause of stridor needs to
      be established. It is important that rare lesions such as teratomas and laryngeal
      cysts are not overlooked; a high index of suspicion for these congenital
      anomalies is necessary. These airway lesions should be managed in an
      institutional setting by a multidisciplinary team.

PMID- 23171624
TI  - Near-infrared quantum cutting in Ho3+, Yb3+-codoped BaGdF5 nanoparticles via
      first-  and second-order energy transfers.
AB  - Infrared quantum cutting involving Yb3+ 950-1,000 nm (2 F5/2 -> 2 F7/2) and Ho3+
      1,007 nm (5S2,5F4 -> 5I6) as well as 1,180 nm (5I6 -> 5I8) emissions is achieved
      in BaGdF5: Ho3+, Yb3+ nanoparticles which are synthesized by a facile
      hydrothermal route. The mechanisms through first- and second-order energy
      transfers were analyzed by the dependence of Yb3+ doping concentration on the
      visible and infrared emissions, decay lifetime curves of the 5 F5 -> 5I8, 5S2/5F4
      -> 5I8, and 5 F3 -> 5I8 of Ho3+, in which a back energy transfer from Yb3+ to
      Ho3+ is first proposed to interpret the spectral characteristics. A modified
      calculation equation for quantum efficiency of Yb3+-Ho3+ couple by exciting at
      450 nm was presented according to the quantum cutting mechanism. Overall, the
      excellent luminescence properties of BaGdF5: Ho3+, Yb3+ near-infrared quantum
      cutting nanoparticles could explore an interesting approach to maximize the
      performance of solar cells.

PMID- 23171625
TI  - The potential of iodine for improving breast cancer diagnosis and treatment.
AB  - Early detection through modalities such as mammography remains pivotal in the
      fight against breast cancer. The detectability of breast cancer through
      mammography is rooted in the differential X-ray attenuation properties of
      cancerous and normal breast tissue. An unexplored component of the X-ray contrast
      between fibrous breast tissue and similarly composed tumor tissue is the presence
      of naturally localized iodine in the cancer but not healthy breast tissue. It is
      hypothesized that differing amounts of iodine are present in tumor versus normal
      breast tissue that leads to more easily detectable cancer due to an increased Z
      value of the tumor tissue relative to the healthy tissue, which results in
      enhanced differences in X-ray attenuation properties between the two tissues and
      thus greater radiographic contrast. The hypothesis is supported by experimental
      observations explaining how iodine could localize in the tumor tissue but not
      surrounding healthy tissue. Breast cancer cells express the sodium-iodide
      symporter (NIS), an ion pump which sequesters iodine in tumor cells. Healthy non
      lactating breast tissue, in contrast, does not express NIS. Further evidence for
      the differential expression of NIS resulting in X-ray contrast enhancement in
      breast cancer is the established correlation between expression of insulin growth
      factor (IGF) and enhanced X-ray contrast, and the evidence that IGF is a promoter
      for NIS. Ultimately, if the expression of iodine can be shown to be a component
      of radiographic contrast between healthy and tumor breast tissue, this could be
      used to drive the development of new technology and techniques for use in the
      detection and treatment of breast cancer. The proof of this hypothesis could thus
      have a substantial impact in the fight against breast cancer.

PMID- 23171626
TI  - C-reactive protein as a predictor of mortality in patients affected with severe
      sepsis in intensive care unit.
AB  - BACKGROUND: Severe sepsis is a primary cause of morbidity and mortality in the
      intensive care unit (ICU). Numerous biomarkers have been assessed to predict
      outcome and CRP is widely used. However, the relevance for mortality risk of the
      CRP level and the day when it is measured have not been well studied. We aimed to
      assess whether initial and/or third dayCRP values are as good predictors of
      mortality in ICU patients with severe sepsis as other well-known complex
      predictors of mortality, i.e., SOFA scores. METHODS: An observational cohort
      study was performed in a 20-bed respiratory ICU in a chest disease center.
      Patients with severe sepsis due to respiratory disease were enrolled in the
      study. SOFA scores, CRP values on admission and on the third day of hospital
      stay, and mortality rate were recorded. ROC curves for SOFA scores and CRP values
      were calculated. RESULTS: The study included 314 ICU patients with sepsis
      admitted between January 2009 and March 2010. The mortality rate was 14.2% (n =
      45). The area under the curve (AUC) for CRP values and SOFA scores on admission
      and on the 3rd day in ICU were calculated as 0.57 (CI: 0.48-0.66); 0.72 (CI: 0.63
      0.80); 0.72 (CI: 0.64-0.81); and 0.76 (CI: 0.67-0.86), respectively. Sepsis due
      to nosocomial infection, a CRP value > 100 mg/L and higher SOFA scores on 3rd
      day, were found to be risk factors for mortality (odds ratio [OR]: 3.76,
      confidence interval [CI]: 1.68-8.40, p < 0.001, OR: 2.70, CI: 1.41-2.01, p <
      0.013, and OR: 1.68, CI: 1.41-2.01, p < 0.0001, respectively). CONCLUSIONS: The
      risk of sepsis related mortality appears to be increased when the 3rd day CRP
      value is greater than 100 mg/dL. Thus, CRP appears to be as valuable a predictor
      of mortality as the SOFA score.

PMID- 23171627
TI  - Farm animal contact as risk factor for transmission of bovine-associated
      Salmonella subtypes.
AB  - Salmonellosis is usually associated with foodborne transmission. To identify risk
      from animal contact, we compared animal exposures of case-patients infected with
      bovine-associated Salmonella subtypes with those of control-patients infected
      with non-bovine-associated subtypes. We used data collected in New York and
      Washington, USA, from March 1, 2008, through March 1, 2010. Contact with farm
      animals during the 5 days before illness onset was significantly associated with
      being a case-patient (odds ratio 3.2, p = 0.0008), after consumption of
      undercooked ground beef and unpasteurized milk were controlled for. Contact with
      cattle specifically was also significantly associated with being a case-patient
      (odds ratio 7.4, p = 0.0002), after food exposures were controlled for. More
      cases of bovine-associated salmonellosis in humans might result from direct
      contact with cattle, as opposed to ingestion of foods of bovine origin, than
      previously recognized. Efforts to control salmonellosis should include a focus on
      transmission routes other than foodborne.

PMID- 23171628
TI  - Motor training of sixty minutes once per week improves motor ability in children
      with congenital heart disease and retarded motor development: a pilot study.
AB  - OBJECTIVE: Delay and impairment of motor development is reported in patients with
      congenital heart disease. This pilot study addressed the feasibility and effect
      of a low-dose motor training programme of 60 min once per week on motor ability
      in preschool children with congenital heart disease. PATIENTS AND METHODS: In
      all, 14 children--including four girls, in the age group of 4-6 years--with
      various types of congenital heart disease performed the motor developmental test
      MOT 4-6 before and after 3 months of a playful exercise programme of 60 min once
      a week. RESULTS: At baseline, the motor quotient ranged from normal to slightly
      impaired (median 92.0; Quartile 1: 83.75; Quartile 3: 101.25). After
      intervention, motor quotient did not change significantly for the entire group
      (95.0 (88.0, 102.5); p50.141). However, in the subgroup of nine children with
      retarded motor development at baseline (motor quotient lower 100), seven children
      had an improved motor quotient after 3 months of intervention. In this subgroup,
      motor quotient increased significantly (p50.020) by 5%. CONCLUSIONS: Overall, a
      short intervention programme of 60 min only once a week does not improve motor
      ability in all children with congenital heart disease. However, those with
      retarded motor development profit significantly from this low-dose intervention.

PMID- 23171629
TI  - Logic modeling and the ridiculome under the rug.
AB  - Logic-derived modeling has been used to map biological networks and to study
      arbitrary functional interactions, and fine-grained kinetic modeling can
      accurately predict the detailed behavior of well-characterized molecular systems;
      at present, however, neither approach comes close to unraveling the full
      complexity of a cell. The current data revolution offers significant promises and
      challenges to both approaches - and could bring them together as it has spurred
      the development of new methods and tools that may help to bridge the many gaps
      between data, models, and mechanistic understanding.

PMID- 23171630
TI  - Cygnet River virus, a novel orthomyxovirus from ducks, Australia.
AB  - A novel virus, designated Cygnet River virus (CyRV), was isolated in embryonated
      eggs from Muscovy ducks in South Australia. CyRV morphologically resembles
      arenaviruses; however, sequencing identified CyRV as an orthomyxovirus. The high
      mortality rate among ducks co-infected with salmonellae suggests that CyRV may be
      pathogenic, either alone or in concert with other infections.

PMID- 23171631
TI  - Psychometric properties of the Intolerance of Uncertainty Scale (IUS) in a
      Chinese-speaking population.
AB  - BACKGROUND: Studies have shown that the intolerance of uncertainty may play a key
      role in the aetiology and maintenance of worry and generalized anxiety disorder.
      AIMS: This study investigated the psychometric properties of the Chinese version
      of Intolerance of Uncertainty Scale (IUS), which had already been validated in
      French and English versions. METHOD: In a large college student sample (N = 940),
      the factor analysis and regression analyses were performed on the IUS. RESULTS:
      The IUS had excellent internal consistency (alpha = 0.90) and good test-retest
      reliability (r = 0.75) over a 5-week period. Factor analysis showed that the IUS
      had a four-factor solution. Finally, the regression analysis demonstrated that IU
      contributed significantly to worry, after controlling for demographic variables
      and levels of anxiety and depression. CONCLUSIONS: The Chinese version of the IUS
      was a sound scale for assessing IU and the intolerance of uncertainty was an
      important influencing factor on worry.

PMID- 23171632
TI  - Reverse regulation of soluble receptor for advanced glycation end products and
      proinflammatory factor resistin and S100A12 in Kawasaki disease.
AB  - INTRODUCTION: Kawasaki disease (KD), an acute febrile disease, characterized by
      systemic vasculitis, predominantly affects infants and children under 5 years of
      age. Coronary artery lesions (CALs) are its most critical complication, and the
      etiology remains unknown yet. In order to explore the value of resistin, S100A12
      and soluble receptor for advanced glycation end products (sRAGE) in the
      pathophysiology of KD, we studied the serum levels of resistin, S100A12 and sRAGE
      in different stages of KD. METHODS: Serum levels of resistin, S100A12 and sRAGE
      were measured by enzyme-linked immunosorbent assay (ELISA) method in 15 healthy
      children and 40 KD patients at acute, afebrile and subacute stage. RESULTS: The
      resistin and S100A12 levels, including the ratio of resistin to sRAGE and S100A12
      to sRAGE increased significantly in the acute stage, and decreased progressively
      in the afebrile and subacute stage. However, the sRAGE levels decreased
      significantly in the acute stage, and increased progressively in the afebrile and
      subacute stage. In the acute, afebrile and subacute stage, the resistin levels
      were higher in intravenous immunoglobulin (IVIG) non-responders (0.64 +/- 0.30,
      0.48 +/- 0.35, 0.28 +/- 0.19, * 102 ng/ml) than in IVIG responders (0.35 +/-
      0.24, 0.21 +/- 0.19, 0.12 +/- 0.05, * 102 ng/ml). In the acute and subacute
      stage, the S100A12 levels were higher in IVIG non-responders (7.92 +/- 2.61, 4.98
      +/- 4.75, * 102 ng/ml) than in IVIG responders (5.05 +/- 3.22, 2.35 +/- 2.26, *
      102 ng/ml). In the afebrile and subacute stage, the sRAGE levels were lower in
      IVIG non-responders (3.51 +/- 2.64, 3.65 +/- 3.27, * 102 pg/ml) than in IVIG
      responders (6.00 +/- 2.78, 7.19 +/- 2.88, * 102 pg/ml). The resistin levels were
      positively correlated with S100A12 levels. The sRAGE levels were negatively
      related with S100A12 and resistin levels. CONCLUSIONS: Resistin, S100A12 and
      sRAGE are involved in the pathophysiology of KD.

PMID- 23171633
TI  - Challenges of the information age: the impact of false discovery on pathway
      identification.
AB  - BACKGROUND: Pathways with members that have known relevance to a disease are used
      to support hypotheses generated from analyses of gene expression and proteomic
      studies. Using cancer as an example, the pitfalls of searching pathways databases
      as support for genes and proteins that could represent false discoveries are
      explored. FINDINGS: The frequency with which networks could be generated from 100
      instances each of randomly selected five and ten genes sets as input to MetaCore,
      a commercial pathways database, was measured. A PubMed search enumerated cancer
      related literature published for any gene in the networks. Using three, two, and
      one maximum intervening step between input genes to populate the network,
      networks were generated with frequencies of 97%, 77%, and 7% using ten gene sets
      and 73%, 27%, and 1% using five gene sets. PubMed reported an average of 4225
      cancer-related articles per network gene. DISCUSSION: This can be attributed to
      the richly populated pathways databases and the interest in the molecular basis
      of cancer. As information sources become enriched, they are more likely to
      generate plausible mechanisms for false discoveries.

PMID- 23171635
TI  - Outbreak of influenza A (H3N2) variant virus infection among attendees of an
      agricultural fair, Pennsylvania, USA, 2011.
AB  - During August 2011, influenza A (H3N2) variant [A(H3N2)v] virus infection
      developed in a child who attended an agricultural fair in Pennsylvania, USA; the
      virus resulted from reassortment of a swine influenza virus with influenza
      A(H1N1)pdm09. We interviewed fair attendees and conducted a retrospective cohort
      study among members of an agricultural club who attended the fair. Probable and
      confirmed cases of A(H3N2)v virus infection were defined by serology and genomic
      sequencing results, respectively. We identified 82 suspected, 4 probable, and 3
      confirmed case-patients who attended the fair. Among 127 cohort study members,
      the risk for suspected case status increased as swine exposure increased from
      none (4%; referent) to visiting swine exhibits (8%; relative risk 2.1; 95% CI 0.2
      53.4) to touching swine (16%; relative risk 4.4; 95% CI 0.8-116.3). Fairs may be
      venues for zoonotic transmission of viruses with epidemic potential; thus, health
      officials should investigate respiratory illness outbreaks associated with
      agricultural events.

PMID- 23171634
TI  - Workshop on research priorities for management and treatment of
      angiostrongyliasis(1).
AB  - In a concluding session of the workshop, the participants developed a list of 115
      research and outreach needs, outlining the top 5-7 needs in each of 8 areas
      (Table). For complete information, including presenter details and abstracts,
      visit the workshop website at www.hawaii.edu/cowielab/Angio%20website%20home.htm.

PMID- 23171636
TI  - Comparison of the effects of electrical stimulation and posterior tibial nerve
      stimulation in the treatment of overactive bladder syndrome.
AB  - AIM: To compare the effects of transvaginal electrical stimulation (ES) and
      posterior tibial nerve stimulation (PTNS) in the treatment of overactive bladder
      syndrome (OAB). METHODS: Women applying with symptoms of urgency, frequency, and
      nocturia with or without incontinence and diagnosed with OAB were divided into an
      ES or PTNS group. Bladder diary, urodynamics, 1-hour pad test, and King's Health
      Questionnaire were performed before and after treatment. ES was applied for 20
      min, 6-8 weeks with pulses of 10-50 Hz square waves at a 300-us or 1-ms pulse
      duration and a maximal output current of 24-60 mA with 5-10 Hz frequency, three
      times per week. PTNS was applied for 30 min once a week for 12 weeks. RESULTS:
      Thirty-five patients received ES, 17 patients received PTNS. Pad test, urinary
      diary, and quality of life parameters after both treatments decreased
      significantly; the decrease in the ES group was greater. The number of patients
      who describe themselves as cured was higher in the ES group. CONCLUSION: PTNS and
      ES are both effective in the treatment of OAB with significant improvement in
      objective and subjective parameters. Objective results show no significant
      difference between the two groups; however, the number of patients who describe
      themselves as cured in the ES group was significantly higher.

PMID- 23171637
TI  - Assessing risk profiles for Salmonella serotypes in breeding pig operations in
      Portugal using a Bayesian hierarchical model.
AB  - BACKGROUND: The EU Regulation No 2160/2003 imposes a reduction in the prevalence
      of Salmonella in pigs. The efficiency of control programmes for Salmonella in
      pigs, reported among the EU Member States, varies and definitive eradication
      seems very difficult. Control measures currently recommended for Salmonella are
      not serotype-specific. Is it possible that the risk factors for different
      Salmonella serotypes are different? The aim of this study was to investigate
      potential risk factors for two groups of Salmonella sp serotypes using pen faecal
      samples from breeding pig holdings representative of the Portuguese pig sector.
      METHODS: The data used come from the Baseline Survey for the Prevalence of
      Salmonella in breeding pigs in Portugal. A total of 1670 pen faecal samples from
      167 herds were tested, and 170 samples were positive for Salmonella. The presence
      of Salmonella in each sample (outcome variable) was classified in three
      categories: i) no Salmonella, ii) Salmonella Typhimurium or S. Typhimurium-like
      strains with the antigenic formula: 1,4,5,12:i:-, , and iii) other serotypes.
      Along with the sample collection, a questionnaire concerning herd management and
      potential risk factors was utilised. The data have a "natural" hierarchical
      structure so a categorical multilevel analysis of the dataset was carried out
      using a Bayesian hierarchical model. The model was estimated using Markov Chain
      Monte Carlo methods, implemented in the software WinBUGS. RESULTS: The
      significant associations found (when compared to category "no Salmonella"), for
      category "serotype Typhimurium or S. Typhimurium-like strains with the antigenic
      formula: 1,4,5,12:i:-" were: age of breeding sows, size of the herd, number of
      pigs/pen and source of semen. For the category "other serotypes" the significant
      associations found were: control of rodents, region of the country, source of
      semen, breeding sector room and source of feed. CONCLUSIONS: The risk factors
      significantly associated with Salmonella shedding from the category "serotype
      Typhimurium or serotype 1,4,5,12:i:-" were more related to animal factors,
      whereas those associated with "other serotypes" were more related to
      environmental factors. Our findings suggest that different control measures could
      be used to control different Salmonella serotypes in breeding pigs.

PMID- 23171639
TI  - New high-cutoff dialyzer allows improved middle molecule clearance without an
      increase in albumin loss: a clinical crossover comparison in extended dialysis.
AB  - BACKGROUND: Accumulation of middle molecules is thought to have adverse effects
      in patients with acute kidney injury (AKI). Elimination of middle molecules by
      non-convective means, i.e. hemodialysis, remains difficult. The aim of the study
      was to investigate the removal characteristics of a new high permeability
      membrane in AKI patients undergoing extended dialysis (ED). PATIENTS AND METHODS:
      We performed a prospective, crossover study comparing the EMiC2 dialyzer (1.8
      m(2), FMC, Germany) and AV 1000S (1.8 m(2), FMC) in 11 critically ill patients
      with AKI. beta2-Microglobulin, cystatin c, creatinine, and urea were measured
      before and after 0.5, 5.0 and 10 h of ED. Serum reduction ratios, dialyzer
      clearances, and mass in the total collected dialysate were determined. RESULTS:
      Dialyzer clearance of beta2-microglobulin (EMiC2: 52 +/- 1.7 ml/min, AV 1000S:
      41.7 +/- 1.5 ml/min, p = 0.0002) and cystatin c (EMiC2: 47.2 +/- 1.2 ml/min, AV
      1000S: 34.2 +/- 2.3 ml/min, p < 0.0001) was markedly different, as was the
      reduction of serum levels of beta2-microglobulin (EMiC2: 54.3 +/- 3.6%, AV 1000S:
      39.1 +/- 4.5%, p = 0.025) and cystatin c (EMiC2: 38.9 +/- 2.6%, AV 1000S: 28.0 +/
      3.9%, p = 0.043). Additionally, we observed a higher total amount of these
      substances in the collected dialysate. There was no significant difference in the
      total amount of albumin eliminated per treatment. CONCLUSION: The new EMiC2
      dialyzer enhances removal of middle molecules without an increase in albumin
      loss. The clinical relevance of this finding needs to be determined.

PMID- 23171638
TI  - APRIL, a proliferation-inducing ligand, as a potential marker of lupus nephritis.
AB  - INTRODUCTION: BLyS and APRIL are cytokines from the tumor necrosis factor family
      which play an important role in systemic lupus erythematosus (SLE). Previous
      works suggested an association between both molecules and SLE disease activity
      although their correlation with lupus nephritis is not known. We therefore
      assessed serum BLyS and APRIL in active lupus nephritis patients. METHODS: Serum
      samples from active lupus nephritis and at 6 months post-treatment were obtained.
      Serum levels of BLyS and APRIL (n = 47) as well as renal mRNA expression were
      measured. Serum levels of both molecules and clinical data (n = 27) were
      available at 6 months follow-up. All biopsy-proven lupus nephritis patients were
      treated with similar immunosuppressive drugs. RESULTS: Serum levels of APRIL were
      associated with proteinuria (Rs = 0.44, P value < 0.01) and degree of
      histological activity (Rs = 0.34; P value < 0.05) whereas BLyS levels were
      associated with complement levels (Rs = 0.46; P value < 0.01) and dosage of
      immunosuppressant. Interestingly, serum APRIL as well as its intrarenal mRNA
      levels were associated with resistance to treatment. From the receiver operating
      characteristic (ROC) analysis, high levels (> 4 ng/mL) of serum APRIL predicted
      treatment failure with a positive predictive value of 93 percent. CONCLUSION:
      APRIL could be a potential biomarker for predicting difficult-to-treat cases of
      lupus nephritis.

PMID- 23171640
TI  - Canine muscle cell culture and consecutive patch-clamp measurements - a new
      approach to characterize muscular diseases in dogs.
AB  - BACKGROUND: The recognition of functional muscular disorders, (e.g.
      channelopathies like Myotonia) is rising in veterinary neurology. Morphologic
      (e.g. histology) and even genetic based studies in these diseases are not able to
      elucidate the functional pathomechanism. As there is a deficit of knowledge and
      skills considering this special task, the aim of the current pilot study was to
      develop a canine muscle cell culture system derived from muscle biopsies of
      healthy client-owned dogs, which allows sampling of the biopsies under working
      conditions in the daily veterinary practise. RESULTS: Muscular biopsies from 16
      dogs of different age and breed were taken during standard surgical procedures
      and were stored for one to three days at 4 degrees C in a transport medium in
      order to simulate shipping conditions. Afterwards biopsies were professionally
      processed, including harvesting of satellite cells, inducing their proliferation,
      differentiating them into myotubes and recultivating myotubes after long-term
      storage in liquid nitrogen. Myogenic origin of cultured cells was determined by
      immunofluorescence, immunohistology and by their typical morphology after
      inducing differentiation. Subsequent to the differentiation into myotubes
      feasibility of patch-clamp recordings of voltage gated ion channels was
      successfully. CONCLUSION: We have developed a canine muscle cell culture system,
      which allows sampling of biopsies from young and old dogs of different breeds
      under practical conditions. Patch clamp measurements can be carried out with the
      cultured myotubes demonstrating potential of these cells as source for functional
      research.

PMID- 23171641
TI  - Psychosocial factors influencing mental health in adults with congenital heart
      disease.
AB  - BACKGROUND: Although adult congenital heart disease (ACHD) patients encounter
      unique challenges related to social adaptation and mental health, only minimal
      research has been conducted on this functioning in Japanese ACHD patients. The
      aims of this study were to describe aspects of the psychosocial functioning of
      ACHD patients and to determine the psychosocial factors influencing their mental
      health. METHODS AND RESULTS: Seventy-two ACHD patients (aged 18-39 years) and 86
      control participants (aged 18-39 years) completed the 36-item Short Form Health
      Survey, a measure of mental health, and 4 self-report questionnaires measuring
      aspects of psychosocial functioning: Independent-Consciousness, Problem-solving,
      Locus of Control, and Self-esteem. Compared to the control group, ACHD patients
      had significantly lower scores for Independence, Problem-solving, and Self
      esteem; whereas they had higher scores for Dependence on Parents. To examine the
      psychosocial factors influencing mental health, a structural equation model was
      used. The psychosocial factor Problem-solving was found to have the most direct
      influence on mental health. This factor was associated with Independence and Self
      esteem. CONCLUSIONS:  ACHD patients in Japan have psychosocial difficulties, and
      the psychosocial factors influencing patients' mental health are social problem
      solving, independence, and self-esteem. The patients have poorer abilities than
      the control group in all of these areas and hence, they run the risk of
      developing poor mental health. 

PMID- 23171642
TI  - T-wave alternans and heart rate turbulence in patients after myocardial in
      farction.

PMID- 23171643
TI  - T-wave alternans and heart rate turbulence in patients after myocardial
      infarction- reply.

PMID- 23171645
TI  - Post-operative respiratory distress following primary cleft palate repair.
AB  - INTRODUCTION: Infants are obligate nasal breathers. Cleft palate closure may
      result in upper airway compromise. We describe children undergoing corrective
      palatal surgery who required unplanned airway support. SETTING: Tertiary referral
      unit. METHOD: Retrospective study (2007-2009) of 157 cleft palate procedures (70
      primary procedures) in 43 patients. Exclusion criteria comprised combined cleft
      lip and palate, secondary palate procedure, and pre-existing airway support.
      RESULTS: The children's mean age was 7.5 months and their mean weight 7.72 kg.
      Eight children were syndromic, and eight underwent pre-operative sleep studies
      (five positive, three negative). Post-operatively, five developed respiratory
      distress and four required oxygen, both events significantly associated with pre
      operative obstructive sleep apnoea (p = 0.001 and 0.015, respectively). Four
      desaturated within 24 hours. Five required a nasopharyngeal airway. Hospital stay
      (mean, 4 days) was significantly associated with obstructive sleep apnoea (p =
      0.002) and nasopharyngeal airway insertion (p = 0.017). DISCUSSION: Pre-operative
      obstructive sleep apnoea correlated significantly with post-operative respiratory
      distress, supplementary oxygen requirement, nasopharyngeal airway insertion and
      hospital stay. We recommend pre-operative sleep investigations for all children
      undergoing cleft palate repair, to enable appropriate timing of the procedure.

PMID- 23171644
TI  - Workshop on treatment of and postexposure prophylaxis for Burkholderia
      pseudomallei and B. mallei Infection, 2010.
AB  - The US Public Health Emergency Medical Countermeasures Enterprise convened
      subject matter experts at the 2010 HHS Burkholderia Workshop to develop consensus
      recommendations for postexposure prophylaxis against and treatment for
      Burkholderia pseudomallei and B. mallei infections, which cause melioidosis and
      glanders, respectively. Drugs recommended by consensus of the participants are
      ceftazidime or meropenem for initial intensive therapy, and
      trimethoprim/sulfamethoxazole or amoxicillin/clavulanic acid for eradication
      therapy. For postexposure prophylaxis, recommended drugs are
      trimethoprim/sulfamethoxazole or co-amoxiclav. To improve the timely diagnosis of
      melioidosis and glanders, further development and wide distribution of rapid
      diagnostic assays were also recommended. Standardized animal models and B.
      pseudomallei strains are needed for further development of therapeutic options.
      Training for laboratory technicians and physicians would facilitate better
      diagnosis and treatment options.

PMID- 23171647
TI  - Sequence based analysis of U-2973, a cell line established from a double-hit B
      cell lymphoma with concurrent MYC and BCL2 rearrangements.
AB  - BACKGROUND: Double-hit lymphoma is a complex and highly aggressive sub-type of B
      cell lymphoma, which has recently been classified and is an area of active
      research interest due to the poor prognosis for patients with this disease. It is
      characterized by the presence of both an activating MYC chromosomal translocation
      and a simultaneous additional oncogenic translocation, often of the BCL2 gene.
      Recently, a cell line was established from a patient with this complex lymphoma
      and analyzed using conventional tools revealing it contains both MYC and BCL2
      translocation events. FINDINGS: In this work, we reanalyzed the genome of the
      cell line using next generation whole genome sequencing technology in order to
      catalogue translocations, insertions and deletions which may contribute to the
      pathology of this lymphoma type. CONCLUSIONS: We describe the cell line in much
      greater detail, and pinpoint the exact locations of the chromosomal breakpoints.
      We also find several rearrangements within cancer-associated genes, which were
      not found using conventional tools, suggesting that high throughput sequencing
      may reveal novel targets for therapy, which could be used concurrently with
      existing treatments.

PMID- 23171648
TI  - Methodological quality of English-language genetic guidelines on hereditary
      breast-cancer screening and management: an evaluation using the AGREE instrument.
AB  - BACKGROUND: We examined the methodological quality of guidelines on syndromes
      conferring genetic susceptibility to breast cancer. METHODS: PubMed, EMBASE, and
      Google were searched for guidelines published up to October 2010. All guidelines
      in English were included. The Appraisal of Guidelines, Research and Evaluation
      (AGREE) instrument was used to assess the quality of the guidelines, and their
      reported evidence base was evaluated. RESULTS: Thirteen guidelines were deemed
      eligible: seven had been developed by independent associations, and the other six
      had national/state endorsements. Four guidelines performed satisfactorily,
      achieving a score of greater than 50% in all six AGREE domains. Mean +/- SD
      standardized scores for the six AGREE domains were: 90 +/- 9% for 'scope and
      purpose', 51 +/- 18% for 'stakeholder involvement', 55 +/- 27% for 'rigour of
      development', 80 +/- 11% for 'clarity and presentation', 37 +/- 32% for
      'applicability', and 47 +/- 38% for 'editorial independence'. Ten of the thirteen
      guidelines were found to be based on research evidence. CONCLUSIONS: Given the
      ethical implications and the high costs of genetic testing for hereditary breast
      cancer, guidelines on this topic should provide clear and evidence-based
      recommendations. Our analysis shows that there is scope for improving many
      aspects of the methodological quality of current guidelines. The AGREE instrument
      is a useful tool, and could be used profitably by guidelines developers to
      improve the quality of recommendations.

PMID- 23171649
TI  - High diversity of RNA viruses in rodents, Ethiopia.
AB  - We investigated synanthropic small mammals in the Ethiopian Highlands as
      potential reservoirs for human pathogens and found that 2 rodent species, the
      Ethiopian white-footed mouse and Awash multimammate mouse, are carriers of novel
      Mobala virus strains. The white-footed mouse also carries a novel hantavirus, the
      second Murinae-associated hantavirus found in Africa.

PMID- 23171650
TI  - An applied research intervention: breast cancer and preventive services in
      African American women.
AB  - INTRODUCTION: The Surveillance Epidemiology and End Results Program 2000-2006
      data reported that African American women experienced a higher incidence of early
      onset invasive breast cancer and in situ breast cancer in comparison with other
      racial/ethnic groups. Of the total of 25,100 cases reported; in situ breast
      cancer represented 6,460 cases and invasive breast cancer represented 18,640
      cases. This intervention focused on women younger than 40 years to increase
      understanding and the utilization of preventive services. METHOD: Over a course
      of 10 months, the researcher designed, implemented, and evaluated an evidence
      based breast cancer course intervention integrating the health belief model. The
      methodology was implemented in 4-week cohorts through in-class and asynchronous
      learning-centered environments tailored to African American women aged 20 to 39
      years at 2-year and 4-year postsecondary schools and culturally relevant
      community-based organizations. RESULTS: The intervention was statistically
      significant, improving understanding of breast cancer in African American women
      in a classroom environment, p < .039, and in an online environment, p < .05. The
      study compared ages 20 to 29 and 30 to 39, finding high agreement and no
      statistically significance difference related to age about the use of preventive
      services, importance of preventive services, and tailoring preventive service for
      younger women. CONCLUSIONS: The intervention demonstrated the implementation of
      an evidence-based breast cancer intervention that improved understanding of
      breast cancer in this race/ethnicity. Additionally, there is a strong need to
      improve preventive services through the integration of evidence-based educational
      interventions targeting women of African American prior to age 40.

PMID- 23171651
TI  - Mental health promotion in a school community by using the results from the Well
      being Profile: an action research project.
AB  - This article presents an action research project as a method to combine science
      and practical expertise in order to develop the practices of the health care
      system. The project aimed at developing mental health promotion in the school
      community in general and at finding tools for timely help when mental health is
      at risk. The underlying idea is that mental health is an integral part of health
      and by promoting general well-being it is also possible to promote and ensure
      mental health at school. The study was conducted in a Finnish lower secondary
      school of 446 pupils where the pupils are aged between 12 and 15 years. The
      initial survey was conducted using the School Well-being Profile, a tool
      developed by Anne Konu. A well-being questionnaire was used to identify the areas
      in need of improvement, providing the basis for planning and implementing
      development measures together with the local actors. The instrument proved to be
      a usable way of collecting feedback of the well-being of the school environment.
      As a result of the action research project, the school's physical conditions and
      social relationships improved and appropriate practices for future problem
      situations were set. 

PMID- 23171652
TI  - Written and spoken narratives about health and cancer decision making: a novel
      application of photovoice.
AB  - Photovoice is a community-based participatory research method that researchers
      have used to identify and address individual and community health needs. We
      developed an abbreviated photovoice project to serve as a supplement to a
      National Cancer Institute-funded pilot study focusing on prostate cancer (PrCA)
      that was set in a faith-based African American community in South Carolina. We
      used photovoice for three reasons: (a) to enhance communication between study
      participants and researchers, (b) to empower African American men and women to
      examine their health decisions through photographs, and (c) to better understand
      how participants from this community make health-related decisions. The 15
      individuals participating in the photovoice project were asked to photograph
      aspects of their community that informed their health-related decisions.
      Participants provided written and oral narratives to describe the images in a
      small sample of photographs. Four primary themes emerged in participants'
      photographs and narratives: (a) food choices, (b) physical activity practices,
      (c) community environment and access to care, and (d) influences of spirituality
      and nature on health. Although written and audio-recorded narratives were similar
      in content, the audio-recorded responses were more descriptive and emotional.
      Results suggest that incorporating audio-recorded narratives in community
      photovoice presentations may have a greater impact than written narratives on
      health promotion, decision making, and policy makers because of an increased
      level of detail and personalization. In conclusion, photovoice strengthened the
      parent study and empowered participants by making them more aware of factors
      influencing their health decisions. 

PMID- 23171653
TI  - Reconciling preferences and constraints in online peer support for youth with
      asthma and allergies.
AB  - In this article, we examine the opportunities and constraints of professionally
      mediated social networking in health promotion practice. Our analysis is based on
      the findings of a 12-week participatory study of a peer-led support intervention
      for youth with asthma and life-threatening allergies. The article begins with an
      overview of the preferences of youth, their parents, and young adults recruited
      as peer mentors for online features in the design of a customized support
      program. We then briefly explain the rationale behind our decision to design and
      host our intervention using a publicly available website called Ability Online in
      an effort to balance participants' preferences with important research
      obligations and safety requirements. Finally, we report on participants' level of
      satisfaction with the intervention as well as recommendations for health
      practitioners who wish to use social networking to enhance supports for youth
      with chronic health conditions. 

PMID- 23171654
TI  - Subclinical influenza virus A infections in pigs exhibited at agricultural fairs,
      Ohio, USA, 2009-2011.
AB  - Agricultural fairs are associated with bidirectional, interspecies transmission
      of influenza virus A between humans and pigs. We examined pigs exhibited at
      agricultural fairs in Ohio during 2009-2011 for signs of influenza-like illness
      and collected nasal swab specimens from a representative subset of these animals.
      Influenza virus A was recovered from pigs at 12/53 (22.6%) fairs during the 3
      year sampling period. Pigs at 10/12 (83.3%) fairs from which influenza virus A
      was recovered did not show signs of influenza-like illness. Hemagglutinin,
      neuraminidase, and matrix gene combinations of the isolates were consistent with
      influenza virus A concurrently circulating among swine herds in the United
      States. Subclinical influenza virus A infections in pigs at agricultural fairs
      may pose a risk to human health and create challenges for passive surveillance
      programs for influenza virus A in swine herds.

PMID- 23171655
TI  - Expression and functional characterization of retinoic acid-inducible gene-I-like
      receptors of mast cells in response to viral infection.
AB  - To investigate the precise mechanisms of virus recognition by mast cells, the
      expression and functional characteristics of virus recognition receptors that
      lead to mast cell activation were investigated. Our results suggest that mast
      cells are partly responsible for the early in vivo production of antiviral
      cytokines and chemokines upon vesicular stomatitis virus (VSV) infection.
      Analysis of the expression of double-stranded RNA (dsRNA) recognition receptors
      in murine bone marrow-derived mast cells (BMMCs) revealed that BMMCs express
      melanoma differentiation-associated gene 5 (MDA5), protein kinase RNA-activated,
      retinoic acid-inducible gene-I (RIG-I) and Toll-like receptor 3. The expression
      levels of these receptors were found to increase upon stimulation of mast cells
      with VSV as well as synthetic dsRNA: polyinosinic-polycytidylic acid. Moreover,
      small interfering RNA analysis to identify the receptors responsible for mast
      cell activation by VSV revealed that both RIG-I and MDA5 were involved in
      cytokine production but not in the degranulation of mast cells. Our findings
      suggest that mast cells produce cytokines and chemokines in the early infection
      stage after recognizing viruses via RIG-I and MDA5, and may contribute to
      antiviral responses. These data provide additional novel information that
      improves our understanding of antiviral innate responses that involve mast cells.

PMID- 23171656
TI  - Pyrazolo[1,5-c]quinazoline derivatives and their simplified analogues as
      adenosine receptor antagonists: synthesis, structure-affinity relationships and
      molecular modeling studies.
AB  - A number of 5-oxo-pyrazolo[1,5-c]quinazolines (series B-1), bearing at position-2
      the claimed (hetero)aryl moiety (compounds 1-8) but also a carboxylate group (9
      14), were designed as hA(3) AR antagonists. This study produced some interesting
      compounds endowed with good hA(3) receptor affinity and high selectivity, being
      totally inactive at all the other AR subtypes. In contrast, the corresponding 5
      ammino derivatives (series B-2) do not bind or bind with very low affinity at the
      hA(3) AR, the only exception being the 5-N-benzoyl compound 19 that shows a
      hA(3)K(i) value in the high MU-molar range. Evaluation of the synthetic
      intermediates led to the identification of some 5(3)-(2-aminophenyl)-3(5)
      (hetero)arylpyrazoles 20-24 with modest affinity but high selectivity toward the
      hA(3) AR subtype. Molecular docking of the herein reported tricyclic and
      simplified derivatives was carried out to depict their hypothetical binding mode
      to our model of hA(3) receptor.

PMID- 23171657
TI  - Drop the Salt! Assessing the impact of a public health advocacy strategy on
      Australian government policy on salt.
AB  - OBJECTIVE: In 2007 the Australian Division of World Action on Salt and Health
      (AWASH) launched a campaign to encourage the Australian government to take action
      to reduce population salt intake. The objective of the present research was to
      assess the impact of the Drop the Salt! campaign on government policy. DESIGN: A
      review of government activities related to salt reduction was conducted and an
      advocacy strategy implemented to increase government action on salt. Advocacy
      actions were documented and the resulting outcomes identified. An analysis of
      stakeholder views on the effectiveness of the advocacy strategy was also
      undertaken. Settings Advocacy activities were coordinated through AWASH at the
      George Institute for Global Health in Sydney. SUBJECTS: All relevant State and
      Federal government statements and actions were reviewed and thirteen stakeholders
      with known interests or responsibilities regarding dietary salt, including food
      industry, government and health organisations, were interviewed. RESULTS:
      Stakeholder analysis affirmed that AWASH influenced the government's agenda on
      salt reduction and four key outputs were attributed to the campaign: (i) the Food
      Regulation Standing Committee discussions on salt, (ii) the Food and Health
      Dialogue salt targets, (iii) National Health and Medical Research Council
      partnership funding and (iv) the New South Wales Premier's Forum on Fast Foods.
      CONCLUSIONS: While it is not possible to definitively attribute changes in
      government policy to one organisation, stakeholder research indicated that the
      AWASH campaign increased the priority of salt reduction on the government's
      agenda. However, a coordinated government strategy on salt reduction is still
      required to ensure that the potential health benefits are fully realised.

PMID- 23171658
TI  - Excessive bone formation in a mouse model of ankylosing spondylitis is associated
      with decreases in Wnt pathway inhibitors.
AB  - INTRODUCTION: Ankylosing spondylitis (AS) is unique in its pathology where
      inflammation commences at the entheses before progressing to an
      osteoproliferative phenotype generating excessive bone formation that can result
      in joint fusion. The underlying mechanisms of this progression are poorly
      understood. Recent work has suggested that changes in Wnt signalling, a key bone
      regulatory pathway, may contribute to joint ankylosis in AS. Using the
      proteoglycan-induced spondylitis (PGISp) mouse model which displays spondylitis
      and eventual joint fusion following an initial inflammatory stimulus, we have
      characterised the structural and molecular changes that underlie disease
      progression. METHODS: PGISp mice were characterised 12 weeks after initiation of
      inflammation using histology, immunohistochemistry (IHC) and expression
      profiling. RESULTS: Inflammation initiated at the periphery of the intervertebral
      discs progressing to disc destruction followed by massively excessive cartilage
      and bone matrix formation, as demonstrated by toluidine blue staining and IHC for
      collagen type I and osteocalcin, leading to syndesmophyte formation. Expression
      levels of DKK1 and SOST, Wnt signalling inhibitors highly expressed in joints,
      were reduced by 49% and 63% respectively in the spine PGISp compared with control
      mice (P < 0.05) with SOST inhibition confirmed by IHC. Microarray profiling
      showed genes involved in inflammation and immune-regulation were altered.
      Further, a number of genes specifically involved in bone regulation including
      other members of the Wnt pathway were also dysregulated. CONCLUSIONS: This study
      implicates the Wnt pathway as a likely mediator of the mechanism by which
      inflammation induces bony ankylosis in spondyloarthritis, raising the potential
      that therapies targeting this pathway may be effective in preventing this
      process.

PMID- 23171660
TI  - Institutionalization of evidence-informed practices in healthcare settings.
AB  - BACKGROUND: The effective and timely integration of the best available research
      evidence into healthcare practice has considerable potential to improve the
      quality of provided care. Knowledge translation (KT) approaches aim to develop,
      implement, and evaluate strategies to address the research-practice gap. However,
      most KT research has been directed toward implementation strategies that apply
      cognitive, behavioral, and, to a lesser extent, organizational theories. In this
      paper, we discuss the potential of institutional theory to inform KT-related
      research. DISCUSSION: Despite significant research, there is still much to learn
      about how to achieve KT within healthcare systems and practices. Institutional
      theory, focusing on the processes by which new ideas and concepts become accepted
      within their institutional environments, holds promise for advancing KT efforts
      and research. To propose new directions for future KT research, we present some
      of the main concepts of institutional theory and discuss their application to KT
      research by outlining how institutionalization of new practices can lead to their
      ongoing use in organizations. In addition, we discuss the circumstances under
      which institutionalized practices dissipate and give way to new insights and
      ideas that can lead to new, more effective practices. SUMMARY: KT research
      informed by institutional theory can provide important insights into how
      knowledge becomes implemented, routinized, and accepted as institutionalized
      practices. Future KT research should employ both quantitative and qualitative
      research designs to examine the specifics of sustainability,
      institutionalization, and deinstitutionalization of practices to enhance our
      understanding of these complex constructs.

PMID- 23171659
TI  - Online disease management of diabetes: engaging and motivating patients online
      with enhanced resources-diabetes (EMPOWER-D), a randomized controlled trial.
AB  - OBJECTIVE: To evaluate an online disease management system supporting patients
      with uncontrolled type 2 diabetes. MATERIALS AND METHODS: Engaging and Motivating
      Patients Online With Enhanced Resources for Diabetes was a 12-month parallel
      randomized controlled trial of 415 patients with type 2 diabetes with baseline
      glycosylated hemoglobin (A1C) values >=7.5% from primary care sites sharing an
      electronic health record. The intervention included: (1) wirelessly uploaded home
      glucometer readings with graphical feedback; (2) comprehensive patient-specific
      diabetes summary status report; (3) nutrition and exercise logs; (4) insulin
      record; (5) online messaging with the patient's health team; (6) nurse care
      manager and dietitian providing advice and medication management; and (7)
      personalized text and video educational 'nuggets' dispensed electronically by the
      care team. A1C was the primary outcome variable. RESULTS: Compared with usual
      care (UC, n=189), patients in the intervention (INT, n=193) group had
      significantly reduced A1C at 6 months (-1.32% INT vs -0.66% UC; p<0.001). At 12
      months, the differences were not significant (-1.14% INT vs -0.95% UC; p=0.133).
      In post hoc analysis, significantly more INT patients had improved diabetes
      control (>0.5% reduction in A1C) than UC patients at 12 months (69.9 (95% CI 63.2
      to 76.5) vs 55.4 (95% CI 48.4 to 62.5); p=0.006). CONCLUSIONS: A nurse-led,
      multidisciplinary health team can manage a population of diabetic patients in an
      online disease management program. INT patients achieved greater decreases in A1C
      at 6 months than UC patients, but the differences were not sustained at 12
      months. More INT than UC patients achieved improvement in A1C (>0.5% decrease).
      Trial registered in clinical trials.gov: #NCT00542204.

PMID- 23171661
TI  - Myelin is dependent on the Charcot-Marie-Tooth Type 4H disease culprit protein
      FRABIN/FGD4 in Schwann cells.
AB  - Studying the function and malfunction of genes and proteins associated with
      inherited forms of peripheral neuropathies has provided multiple clues to our
      understanding of myelinated nerves in health and disease. Here, we have generated
      a mouse model for the peripheral neuropathy Charcot-Marie-Tooth disease type 4H
      by constitutively disrupting the mouse orthologue of the suspected culprit gene
      FGD4 that encodes the small RhoGTPase Cdc42-guanine nucleotide exchange factor
      Frabin. Lack of Frabin/Fgd4 causes dysmyelination in mice in early peripheral
      nerve development, followed by profound myelin abnormalities and demyelination at
      later stages. At the age of 60 weeks, this was accompanied by
      electrophysiological deficits. By crossing mice carrying alleles of Frabin/Fgd4
      flanked by loxP sequences with animals expressing Cre recombinase in a cell type
      specific manner, we show that Schwann cell-autonomous Frabin/Fgd4 function is
      essential for proper myelination without detectable primary contributions from
      neurons. Deletion of Frabin/Fgd4 in Schwann cells of fully myelinated nerve
      fibres revealed that this protein is not only required for correct nerve
      development but also for accurate myelin maintenance. Moreover, we established
      that correct activation of Cdc42 is dependent on Frabin/Fgd4 function in healthy
      peripheral nerves. Genetic disruption of Cdc42 in Schwann cells of adult
      myelinated nerves resulted in myelin alterations similar to those observed in
      Frabin/Fgd4-deficient mice, indicating that Cdc42 and the Frabin/Fgd4-Cdc42 axis
      are critical for myelin homeostasis. In line with known regulatory roles of
      Cdc42, we found that Frabin/Fgd4 regulates Schwann cell endocytosis, a process
      that is increasingly recognized as a relevant mechanism in peripheral nerve
      pathophysiology. Taken together, our results indicate that regulation of Cdc42 by
      Frabin/Fgd4 in Schwann cells is critical for the structure and function of the
      peripheral nervous system. In particular, this regulatory link is continuously
      required in adult fully myelinated nerve fibres. Thus, mechanisms regulated by
      Frabin/Fgd4-Cdc42 are promising targets that can help to identify additional
      regulators of myelin development and homeostasis, which may crucially contribute
      also to malfunctions in different types of peripheral neuropathies.

PMID- 23171663
TI  - Luteolin inhibits angiotensin II-induced human umbilical vein endothelial cell
      proliferation and migration through downregulation of Src and Akt
      phosphorylation.
AB  - BACKGROUND: The proliferation and migration of vascular endothelial cells (VECs)
      plays a vital role in angiogenesis, a process that influences plaque
      vulnerability in human atherosclerosis. Luteolin is a type of flavonoid that has
      shown a positive effect on the morbidity and mortality of cardiovascular
      diseases. However, it remains unclear whether this compound has a protective
      effect against the proliferation and migration of human umbilical vein
      endothelial cells (HUVECs) induced by angiotensin II (AngII). METHODS AND
      RESULTS:  HUVECs were treated with different concentrations of luteolin for
      varying lengths of time. Analysis using methyl thiazolyl tetrazolium and 5
      ethynyl-2'-deoxyuridine revealed that 25 MUmol/L luteolin had a particularly
      inhibitory effect on the AngII-induced proliferation of HUVECs. A Transwell
      chamber was then used to assay the migration of HUVECs in the presence of 12.5
      MUmol/L luteolin. The results showed that the migration of AngII-induced HUVECs
      was also inhibited by luteolin. Further investigations showed that the
      phosphorylation levels of Src, p-Akt (308), and p-Akt (473) in the group treated
      with both luteolin and AngII were significantly lower than those of the group
      treated with only AngII. CONCLUSIONS: The inhibitory effects of luteolin on the
      proliferation and migration of VECs stimulated by AngII are mediated through the
      downregulation of the PI3K/Akt signaling pathway.

PMID- 23171662
TI  - The dorsal stream contribution to phonological retrieval in object naming.
AB  - Meaningful speech, as exemplified in object naming, calls on knowledge of the
      mappings between word meanings and phonological forms. Phonological errors in
      naming (e.g. GHOST named as 'goath') are commonly seen in persisting post-stroke
      aphasia and are thought to signal impairment in retrieval of phonological form
      information. We performed a voxel-based lesion-symptom mapping analysis of 1718
      phonological naming errors collected from 106 individuals with diverse profiles
      of aphasia. Voxels in which lesion status correlated with phonological error
      rates localized to dorsal stream areas, in keeping with classical and
      contemporary brain-language models. Within the dorsal stream, the critical voxels
      were concentrated in premotor cortex, pre- and postcentral gyri and supramarginal
      gyrus with minimal extension into auditory-related posterior temporal and temporo
      parietal cortices. This challenges the popular notion that error-free
      phonological retrieval requires guidance from sensory traces stored in posterior
      auditory regions and points instead to sensory-motor processes located further
      anterior in the dorsal stream. In a separate analysis, we compared the lesion
      maps for phonological and semantic errors and determined that there was no
      spatial overlap, demonstrating that the brain segregates phonological and
      semantic retrieval operations in word production.

PMID- 23171664
TI  - Nasal tip abscess due to adverse skin reaction to Prolene: an unusual long term
      complication of rhinoplasty.
AB  - OBJECTIVES: Allergic reactions to Prolene are rare. This paper reports a nasal
      tip abscess which developed in a patient with an adverse skin reaction to Prolene
      after rhinoplasty. METHODS AND RESULTS: A 26-year-old woman presented with
      painful, progressive nasal tip swelling and redness. She had undergone septo
      rhinoplasty two years previously. She was initially treated with endonasal
      drainage of the abscess and antibiotics, but a revision rhinoplasty three months
      later became necessary because of recurrent abscess formation. Intra-operative
      findings included granulation tissue with pockets of pus and knotted Prolene
      sutures at the tip-defining points of the lower lateral cartilages. She was patch
      tested with Prolene and a cutaneous Prolene suture was placed on her back; an
      adverse skin reaction was seen for the latter. CONCLUSION: Use of non-absorbable
      sutures, such as Prolene, in the subcutaneous layer may be a potential, rare risk
      factor for adverse skin reactions.

PMID- 23171665
TI  - Tick parasites of rodents in Romania: host preferences, community structure and
      geographical distribution.
AB  - BACKGROUND: Ticks are among the most important vectors of zoonotic diseases in
      temperate regions of Europe, with widespread distribution and high densities,
      posing an important medical risk. Most ticks feed on a variety of progressively
      larger hosts, with a large number of small mammal species typically harbouring
      primarily the immature stages. However, there are certain Ixodidae that
      characteristically attack micromammals also during their adult stage. Rodents are
      widespread hosts of ticks, important vectors and competent reservoirs of tick
      borne pathogens. Micromammal-tick associations have been poorly studied in
      Romania, and our manuscript shows the results of a large scale study on tick
      infestation epidemiology in rodents from Romania. METHODS: Rodents were caught
      using snap-traps in a variety of habitats in Romania, between May 2010 and
      November 2011. Ticks were individually collected from these rodents and
      identified to species and development stage. Frequency, mean intensity,
      prevalence and its 95% confidence intervals were calculated using the EpiInfo
      2000 software. A p value of <0.05 was considered statistically significant.
      RESULTS: We examined 423 rodents (12 species) collected from six counties in
      Romania for the presence of ticks. Each collected tick was identified to species
      level and the following epidemiological parameters were calculated: prevalence,
      mean intensity and mean abundance. The total number of ticks collected from
      rodents was 483, with eight species identified: Ixodes ricinus, I. redikorzevi,
      I. apronophorus, I. trianguliceps, I. laguri, Dermacentor marginatus,
      Rhipicephalus sanguineus and Haemaphysalis sulcata. The overall prevalence of
      tick infestation was 29.55%, with a mean intensity of 3.86 and a mean abundance
      of 1.14. Only two polyspecific infestations were found: I. ricinus + I.
      redikorzevi and I. ricinus + D. marginatus. CONCLUSIONS: Our study showed a
      relatively high diversity of ticks parasitizing rodents in Romania. The most
      common tick in rodents was I. ricinus, followed by I. redikorzevi. Certain
      rodents seem to host a significantly higher number of tick species than others,
      the most important within this view being Apodemus flavicollis and Microtus
      arvalis. The same applies for the overall prevalence of tick parasitism, with
      some species more commonly infected (M. arvalis, A. uralensis, A. flavicollis and
      M. glareolus) than others. Two rodent species (Mus musculus, Rattus norvegicus)
      did not harbour ticks at all. Based on our results we may assert that rodents
      generally can act as good indicators for assessing the distribution of certain
      tick species.

PMID- 23171666
TI  - Phenolic compounds and interaction between aminoglycosides and natural products
      of Lygodium venustum SW against multiresistant bacteria.
AB  - BACKGROUND: The aim of this work was to evaluate the interactions between
      aminoglycosides and the ethyl-acetate fraction of the fern Lygodium venustum SW
      (EAFLV) METHODS: The ethyl-acetate fraction was obtained from the ethanol extract
      of L. venustum and was assayed via the checkerboard method associated with
      aminoglycosides against two bacterial strains multiresistant to antibiotics.
      RESULTS: The antibiotic activity of all drugs, when associated with the ethyl
      acetate fraction, was enhanced in an additive manner, except for the association
      between EAFLV and amikacin, which showed a synergistic interaction against the
      Escherichia coli strain. CONCLUSIONS: The results indicated that L. venustum can
      be a source of secondary metabolites to be used in association with antibiotics
      like aminoglycosides in antibiotic chemotherapy against resistant bacteria.

PMID- 23171668
TI  - West Nile virus neurologic disease in humans, South Africa, September 2008-may
      2009.
AB  - We investigated West Nile virus (WNV) as a possible disease etiology in persons
      hospitalized in South Africa. Of 206 specimens tested, 36 had WNV neutralizing
      antibodies, significantly more than in similar earlier serosurveys. Seven
      probable acute WNV cases were identified, suggesting WNV may be overlooked as an
      etiology of severe disease in South Africa.

PMID- 23171669
TI  - Complex regional pain syndrome acceptance and the alternative denominations in
      the medical literature.
AB  - OBJECTIVE: To analyze the use of the term 'complex regional pain syndrome' in the
      medical literature and evaluate whether or not the traditional names 'reflex
      sympathetic dystrophy' and 'causalgia' have already been replaced with the new
      terms 'complex regional pain syndrome type I' and 'complex regional pain syndrome
      type II', respectively. MATERIALS AND METHODS: The Scopus and PubMed databases
      were searched for reports written between 2001 and 2012 for the following
      descriptors in the titles: 'complex regional pain syndrome', 'complex regional
      pain syndrome type I', 'complex regional pain syndrome type 1', 'complex regional
      pain syndrome type II', 'complex regional pain syndrome type 2', 'CRPS', 'CRPS
      type I', 'CRPS type 1', 'CRPS type II', 'CRPS type 2', 'reflex sympathetic
      dystrophy', 'algodystrophy', 'algoneurodystrophy', 'causalgia', 'transient
      osteoporosis', 'Sudeck', and 'shoulder-hand syndrome'. RESULTS: Systematization
      of the 1,318 articles found yielded the following: 953 (72.31%) articles for the
      descriptor 'complex regional pain syndrome' and a further 94 (7.13%) for its
      abbreviation 'CRPS'; 180 (13.66%) for 'reflex sympathetic dystrophy'; 33 (2.50%)
      for 'shoulder-hand syndrome'; 29 (2.20%) for 'algodystrophy'; 13 (0.99%) for
      'causalgia'; 13 (0.99%) for 'Sudeck'; 2 (0.15%) for 'algoneurodystrophy', and 1
      (0.08%) for 'transient osteoporosis'. The total number of articles using new
      terminology represents 1,047 (79.44%) of all articles. CONCLUSION: The new
      neutral term 'complex regional pain syndrome' was most commonly used and will
      likely replace the traditional names 'reflex sympathetic dystrophy' and
      'causalgia'. The new terminology is now widely accepted by the medical
      professionals who are mostly engaged in the treatment of CRPS patients, but not
      yet so in other medical spheres.

PMID- 23171670
TI  - Reducing sodium intake at the community level: the sodium reduction in
      communities program.

PMID- 23171671
TI  - Multisite qualitative study of primary care physicians' and midlevel providers'
      self-reported practices and perceptions about maintaining cognitive health.
AB  - INTRODUCTION: To facilitate national efforts to maintain cognitive health through
      public health practice, the Healthy Brain Initiative recommended examining
      diverse groups to identify stakeholder perspectives on cognitive health. In
      response, the Healthy Aging Research Network (HAN), funded by the Centers for
      Disease Control and Prevention (CDC), coordinated projects to document the
      perspectives of older adults, caregivers of people with dementia, and primary
      care providers (PCPs) on maintaining cognitive health. Our objective was to
      describe PCPs' perceptions and practices regarding cognitive health. METHODS: HAN
      researchers conducted 10 focus groups and 3 interviews with physicians (N = 28)
      and advanced practice providers (N = 21) in Colorado, Texas, and North Carolina
      from June 2007 to November 2008. Data were transcribed and coded axially.
      RESULTS: PCPs reported addressing cognitive health with patients only indirectly
      in the context of physical health or in response to observed functional changes
      and patient or family requests. Some providers felt evidence on the efficacy of
      preventive strategies for cognitive health was insufficient, but many reported
      suggesting activities such as games and social interaction when queried by
      patients. PCPs identified barriers to talking with patients about cognitive
      health such as lack of time and patient reactions to recommendations. CONCLUSION:
      Communicating new evidence on cognitive health and engaging older adults in
      making lasting lifestyle changes recommended by PCPs and others may be practical
      ways in which public health practitioners can partner with PCPs to address
      cognitive health in health care settings.

PMID- 23171672
TI  - Implementation strategies of internet-based asthma self-management support in
      usual care. Study protocol for the IMPASSE cluster randomized trial.
AB  - BACKGROUND: Internet-based self-management (IBSM) support cost-effectively
      improves asthma control, asthma related quality of life, number of symptom-free
      days, and lung function in patients with mild to moderate persistent asthma. The
      current challenge is to implement IBSM in clinical practice. METHODS/DESIGN: This
      study is a three-arm cluster randomized trial with a cluster pre-randomisation
      design and 12 months follow-up per practice comparing the following three IBSM
      implementation strategies: minimum strategy (MS): dissemination of the IBSM
      program; intermediate strategy (IS): MS + start-up support for professionals
      (i.e., support in selection of the appropriate population and training of
      professionals); and extended strategy (ES): IS + additional training and ongoing
      support for professionals. Because the implementation strategies (interventions)
      are primarily targeted at general practices, randomisation will occur at practice
      level.In this study, we aim to evaluate 14 primary care practices per strategy in
      the Leiden-The Hague region, involving 140 patients per arm. Patients aged 18 to
      50 years, with a physician diagnosis of asthma, prescription of inhaled
      corticosteroids, and/or montelukast for >=3 months in the previous year are
      eligible to participate. Primary outcome measures are the proportion of referred
      patients that participate in IBSM, and the proportion of patients that have
      clinically relevant improvement in the asthma-related quality of life. The
      secondary effect measures are clinical outcomes (asthma control, lung function,
      usage of airway treatment, and presence of exacerbations); self-management
      related outcomes (health education impact, medication adherence, and illness
      perceptions); and patient utilities. Process measures are the proportion of
      practices that participate in IBSM and adherence of professionals to
      implementation strategies. Cost-effective measurements are medical costs and
      healthcare consumption. Follow-up is six months per patient. DISCUSSION: This
      study provides insight in the amount of support that is required by general
      practices for cost-effective implementation of IBSM. Additionally, design and
      results can be beneficial for implementation of other self-management initiatives
      in clinical practice. TRIAL REGISTRATION: the Netherlands National Trial Register
      NTR2970.

PMID- 23171673
TI  - Reservoir competence of wildlife host species for Babesia microti.
AB  - Human babesiosis is an increasing health concern in the northeastern United
      States, where the causal agent, Babesia microti, is spread through the bite of
      infected Ixodes scapularis ticks. We sampled 10 mammal and 4 bird species within
      a vertebrate host community in southeastern New York to quantify reservoir
      competence (mean percentage of ticks infected by an individual host) using real
      time PCR. We found reservoir competence levels >17% in white-footed mice
      (Peromyscus leucopus), raccoons (Procyon lotor), short-tailed shrews (Blarina
      brevicauda), and eastern chipmunks (Tamias striatus), and <6% but >0% in all
      other species, including all 4 bird species. Data on the relative contributions
      of multiple host species to tick infection with B. microti and level of genetic
      differentiation between B. microti strains transmitted by different hosts will
      help advance understanding of the spread of human babesiosis.

PMID- 23171674
TI  - In utero exposure to dioxins and dioxin-like compounds and anogenital distance in
      newborns and infants.
AB  - BACKGROUND: Anogenital distance in animals is used as a measure of fetal androgen
      action. Prenatal exposure to dioxins and dioxin-like compounds in rodents causes
      reproductive changes in male offspring and decreases anogenital distance.
      OBJECTIVE: We assessed whether in utero exposure to dioxins and dioxin-like
      compounds adversely influences anogenital distance in newborns and young children
      (median age, 16 months; range, 1-31 months). METHODS: We measured anogenital
      distance among participants of the "Rhea" mother-child cohort study in Crete and
      the Hospital del Mar (HMAR) cohort in Barcelona. Anogenital distance (AGD; anus
      to upper penis), anoscrotal distance (ASD; anus to scrotum), and penis width (PW)
      were measured in 119 newborn and 239 young boys; anoclitoral (ACD; anus to
      clitoris) and anofourchetal distance (AFD; anus to fourchette) were measured in
      118 newborn and 223 young girls. We estimated plasma dioxin-like activity in
      maternal blood samples collected at delivery with the Dioxin-Responsive
      Chemically Activated LUciferase eXpression (DR CALUX(r)) bioassay. RESULTS:
      Anogenital distances were sexually dimorphic, being longer in males than females.
      Plasma dioxin-like activity was negatively associated with AGD in male newborns.
      The estimated change in AGD per 10 pg CALUX(r)-toxic equivalent/g lipid increase
      was -0.44 mm (95% CI: -0.80, -0.08) after adjusting for confounders. Negative but
      smaller and nonsignificant associations were observed for AGD in young boys. No
      associations were found in girls. CONCLUSIONS: Male infants may be susceptible to
      endocrine-disrupting effects of dioxins. Our findings are consistent with the
      experimental animal evidence used by the Food and Agriculture Organization/World
      Health Organization to set recommendations for human dioxin intake.

PMID- 23171675
TI  - Apps for asthma self-management: a systematic assessment of content and tools.
AB  - BACKGROUND: Apps have been enthusiastically adopted by the general public. They
      are increasingly recognized by policy-makers as a potential medium for supporting
      self-management of long-term conditions. We assessed the degree to which current
      smartphone and tablet apps for people with asthma offer content and tools of
      appropriate quality to support asthma self-management. METHODS: We adapted
      systematic review methodology to the assessment of apps. We identified English
      language asthma apps for all ages through a systematic search of official app
      stores. We systematically assessed app content using criteria derived from
      international guidelines and systematic review of strategies for asthma self
      management. We covered three domains: comprehensiveness of asthma information,
      consistency of advice with evidence and compliance with health information best
      practice principles. RESULTS: We identified 103 apps for asthma in English, of
      which 56 were sources of information about the condition and 47 provided tools
      for the management of asthma. No apps offered both types of functionality. Only
      three information apps approached our definition of comprehensiveness of
      information about asthma. No apps provided advice on lay management of acute
      asthma that included details of appropriate reliever medication use. In 32 of 72
      instances, apps made unequivocal recommendations about strategies for asthma
      control or prophylaxis that were unsupported by current evidence. Although 90% of
      apps stated a clear purpose, compliance with other best practice principles for
      health information was variable. Contact details were located for 55%, funding
      source for 18% and confidentiality policy for 17%. CONCLUSIONS: No apps for
      people with asthma combined reliable, comprehensive information about the
      condition with supportive tools for self-management. Healthcare professionals
      considering recommending apps to patients as part of asthma self-management
      should exercise caution, recognizing that some apps like calculators may be
      unsafe; that no current app will meet the need of every patient; and that ways of
      working must be adapted if apps are to be introduced, supported and sustained in
      routine care. Policy-makers need to consider the potential role for assurance
      mechanisms in relation to apps. There remains much to be done if apps are to find
      broad use in clinical practice; clinicians cannot recommend tools that are
      inaccurate, unsafe or lack an evidence base.

PMID- 23171676
TI  - Tissue selective estrogen complexes (TSECs) differentially modulate markers of
      proliferation and differentiation in endometrial cells.
AB  - Selective estrogen receptor modulators (SERMs) have tissue-specific estrogen
      receptor (ER) modulating properties. Combining an SERM with one or more estrogens
      to form a tissue selective estrogen complex (TSEC) can provide an improved blend
      of tissue-specific ER agonist and antagonist effects. While both estrogens and
      SERMs affect the uterine endometrium, not all TSECs reverse the endometrial
      effects of estrogens preventing endometrial proliferation and hyperplasia. Their
      action in uterine cells is not completely understood. HOXA 10, leukemia
      inhibitory factor (LIF), progesterone receptor (PR), and EMX2 are genes known to
      regulate endometrial proliferation and differentiation. The expression of these
      genes was used to assess endometrial effects of SERMs and TSECs. We evaluated the
      effects of raloxifene (RAL), tamoxifen (TAM), lasofoxifene (LAS), bazedoxifene
      acetate (BZA), and progesterone (P) alone and in combination with estradiol (E2)
      in Ishikawa cells. Increased HOXA10, LIF, PR, and EMX2 messenger RNA (mRNA)
      expression was noted in E2-treated cells compared with vehicle-treated controls.
      All TSECs maintained E2-induced PR expression and all except TAM prevented
      estrogen-induced LIF expression. The TSEC containing BZA uniquely decreased
      HOXA10 expression and increased EMX2 expression. The TSECs alter endometrial cell
      proliferation by selective modulation of estrogen responsive genes, maintaining
      the antiproliferative effects mediated by PR and inhibiting LIF. The differential
      effect of TSECs on endometrial gene expression suggests a mechanism by which they
      manifest differential effects on endometrial safety against the risk of estrogen
      induced endometrial hyperplasia.

PMID- 23171677
TI  - High frequency of putative ovarian cancer stem cells with CD44/CK19 coexpression
      is associated with decreased progression-free intervals in patients with
      recurrent epithelial ovarian cancer.
AB  - OBJECTIVE: Epithelial ovarian cancer (EOC) cells with CD44 and CK19 coexpression
      may represent a subset of ovarian cancer stem cells (OCSCs). This study was
      conducted to evaluate the correlation of the frequency of putative OCSCs (CD44 +
      CK19 + OCSCs) with the clinicopathologic features and the prognostic value in
      patients with recurrent advanced stage EOC. METHODS: A retrospective study was
      carried out on 33 patients with EOC and a uniformly treated tissue microarray was
      constructed. A multiplexed, immunofluorescence-based method of automated in situ
      quantitative measurement of protein analysis was used for evaluation of the
      frequency or density of CD44 + CK19 + OCSCs in EOC. RESULTS: The mean follow-up
      time was 42.8 +/- 27.1 months. High frequency of EOC cells with CD44+ or
      CD44+/CK19+ was associated with chemoresistance (P = .033 and P = .02,
      respectively). Using K-M analysis with log-rank test, a high frequency of
      putative OCSCs was associated with short disease-free interval (7.9 months vs
      20.9 months, P = .019). In univariable analysis, the frequency of OCSCs,
      International Federation of Gynecology and Obstetrics stage and residual tumor
      volume were significant predictor variables and were entered into multivariable
      analysis (P = .019, .037, and .005, respectively). Although no independent
      significant predictor was found, the frequency of putative OCSCs was the most
      promising predictor variable compared with the other 2 variables (hazard ratio =
      2.344, P = .052). CONCLUSION: Our findings suggest that high frequency of OCSCs
      (CD44+ and CK19+) in epithelial ovarian tumors correlates with short progression
      free intervals.

PMID- 23171678
TI  - Follistatin is induced by IL-1beta and TNF-alpha in stromal cells from
      endometrioma.
AB  - The aim of this study is to examine the regulation of follistatin, an activin
      binding protein, in endometriosis. Endometrioma stromal cells (EoSCs) were
      obtained from 9 patients undergoing laparoscopy of the ovarian endometrioma. In
      cultured EoSCs, interleukin 1beta (IL-1beta) and tumor necrosis factor-alpha (TNF
      alpha), which could induce activin-A, also induced follistatin messenger RNA
      (mRNA) and protein. The cystic fluid of endometrioma from 8 patients was obtained
      to measure the concentration of activin-A and follistatin by enzyme-linked
      immunosorbent assay (ELISA). Also, activin activity in the fluid was examined by
      erythroid differentiation assay using mouse erythroleukemia F5-5.fl cells. In the
      cystic fluid of endometrioma, the mean values of activin-A and follistatin
      concentration were 36.8 ng/mL and 4.0 ng/mL, respectively. In a bioassay, all 8
      samples exhibited activin activity, which was equivalent to recombinant activin-A
      activity of 12.8 +/- 1.4 ng/mL. Although follistatin was present in the cystic
      fluid of endometrioma, the activity of activin, which is an exacerbation factor
      of endometriosis, was predominant in vivo.

PMID- 23171679
TI  - Somatostatin analogs regress endometriotic implants in rats by decreasing implant
      levels of vascular endothelial growth factor and matrix metaloproteinase 9.
AB  - OBJECTIVE: To examine the effect of somatostatin analogs on surgically induced
      endometriosis in rat models. STUDY DESIGN: Endometrial tissue was implanted onto
      the abdominal peritoneum of 26 rats that were randomized into 3 groups. The rats
      in group 1(n = 9) were subcutaneously administered with 0.02 mg/kg/d of
      octreotide (a short-acting analog)for 28 days . The rats in group 2 (n = 8) were
      subcutaneously injected with 20 mg/kg of a single dose of a long-acting analogue
      lanreotide The rats in group 3 were given no medication and served as controls (n
      = 9). RESULTS: Mean volume and histologic score of implants in groups 1 (P < .01
      and P < .05, respectively) and 2 (P < .01and P < .05, respectively) were
      significantly lower than that in group 3. There were significant reductions in
      vascular endothelial growth factor (VEGF) and matrix metalloproteinase 9 (MMP-9)
      immunoreactivities in group 1 (0.67 +/- 0.50 and 1.22 +/- 0.44, respectively;
      both P < .01) and group 2 (0.71 +/- 0.48 and 0.86 +/- 0.69, respectively; both P
      < .01) when compared with the control group (1.78 +/- 0.83 and 2.11 +/- 0.78,
      respectively). CONCLUSION: Somatostatin analogs has regressed significantly the
      size of the endometriotic implants and caused atrophy of these lesions in rats by
      decreasing explant levels of VEGF and MMP-9.

PMID- 23171680
TI  - Real-time ultrasound assessment of body and breathing movements and abdominal
      diameter in fetal lambs from 55 days of gestation to term.
AB  - We used real-time ultrasound to measure motility and abdominal diameter in fetal
      lambs at weekly intervals for 30 minutes from 55 days to term (n = 8). Fetal body
      movement counts/min were relatively constant between 55 and ~90 days and declined
      progressively thereafter, a relationship best described by piecewise linear
      regression with 2 elements. The break point in the regression curves averaged
      91.9 +/- 5.2 days. The relationship between gestational age and abdominal
      diameter was also best described by piecewise linear regression. The break point
      of 113.1 +/- 3.9 days was significantly greater than the movement break point.
      There was a significant linear relationship between the movement and abdominal
      break points, with the latter occurring 21.6 +/- 6.6 days later. These results
      suggest that both fetal motility and growth may decrease in order to lower fetal
      O2 demands to match the progressive decline in fetal O2 delivery with advancing
      gestation.

PMID- 23171681
TI  - Diabetic rats exercised prior to and during pregnancy: maternal reproductive
      outcome, biochemical profile, and frequency of fetal anomalies.
AB  - The aim of this study was to evaluate the effects of exercise prior to or during
      pregnancy on maternal reproductive outcome, biochemical profile, and on fetal
      anomaly frequency in a rat pregnancy model utilizing chemically induced diabetes.
      Wistar rats (minimum n = 11 animals/group) were randomly assigned the following
      groups: group 1 (G1), sedentary, nondiabetic; G2, nondiabetic, exercised during
      pregnancy; G3, nondiabetic, exercised prior to and during pregnancy; G4,
      sedentary, diabetic; G5, diabetic, exercised during pregnancy; and G6, diabetic,
      exercised prior to and during pregnancy. A swimming program was utilized for
      moderate exercise. On day 21 of pregnancy, all rats were anesthetized to obtain
      blood for biochemical measurements. The gravid uterus was weighed with its
      contents, and the fetuses were analyzed. The nondiabetic rats exercised prior to
      pregnancy presented a reduced maternal weight gain. Besides, G2 and G3 groups
      showed decreased fetal weights at term pregnancy, indicating slight intrauterine
      growth restriction (IUGR). In the diabetic dams, the swimming program did not
      have antihyperglycemic effects. The exercise applied only during pregnancy caused
      severe IUGR, as confirmed by reduced fetal weight mean, fetal weight
      classification, and ossification sites. Nevertheless, exercise was not a
      teratogenic factor and improved the rats' lipid profiles, demonstrating that the
      exercise presented possible benefits, but there are also risks prior and during
      pregnancy, especially in diabetic pregnant women.

PMID- 23171682
TI  - Pregnancy enhances the effects of hypercholesterolemia on posterior cerebral
      arteries.
AB  - In preeclampsia, hyperlipidemia is enhanced compared to normal pregnancy that
      could adversely affect vascular function. In the cerebral vasculature, this could
      lead to dysregulation of cerebral blood flow and neurological complications.
      Here, we examined the effect of excessive hyperlipidemia, as seen in
      preeclampsia, on cerebral artery function and expression of inflammatory markers
      in pregnancy. Pregnant and nonpregnant rats received a 14-day high-cholesterol
      diet or normal chow and posterior cerebral artery function was compared. High
      cholesterol significantly increased sensitivity of posterior cerebral arteries to
      the nitric oxide donor sodium nitroprusside that was accompanied by a ~12-fold
      increased messenger RNA (mRNA) expression of inducible nitric oxide synthase in
      late-pregnant rats only. Further, high cholesterol significantly increased
      peroxynitrite-induced dilation and decreased myogenic tone in cerebral arteries
      from late pregnant compared to nonpregnant animals. These results suggest that
      pathologically high levels of cholesterol in pregnancy enhance inflammatory
      responses and peroxynitrite generation in cerebral arteries.

PMID- 23171683
TI  - Uterine leiomyomas: effects on architectural, cellular, and molecular
      determinants of endometrial receptivity.
AB  - Impaired endometrial receptivity is an important contributing factor to
      implantation failure. Uterine leiomyomas are widely prevalent steroid hormone
      dependent benign tumors that act as a restraint to conception and successful
      outcome of pregnancies. Reports are available, which suggest that leiomyomas have
      negative influence on endometrial receptivity to blastocyst implantation. The aim
      of the present review is to provide a comprehensive picture of the current
      knowledge of the effect of uterine leiomyomas on the architectural, cellular, and
      molecular determinants of endometrial receptivity. Understanding the potential
      role of these factors will provide insight into the underlying mechanisms of
      leiomyoma-associated infertility and provide new areas for basic and
      translational research.

PMID- 23171684
TI  - Siglec-6 expression is increased in placentas from pregnancies complicated by
      preterm preeclampsia.
AB  - Sialic acid immunoglobulin-like lectin (Siglec)-6 is a transmembrane receptor
      that binds sialyl-TN glycans and leptin. Among eutherian mammals, only human
      placentas express Siglec-6. Previous work has implicated Siglec-6 in preeclampsia
      (PE). Preeclampsia, a leading cause of maternal and perinatal morbidity and
      mortality, is characterized by placental abnormalities. This study provides a
      comprehensive analysis of Siglec-6 protein expression during human pregnancy by
      disease state (PE), biologic compartment (basal plate, chorionic villi, or
      maternal plasma), gestational age (24-41 weeks), and labor status. Siglec-6
      protein was increased in both the basal plate and chorionic villi of preterm PE
      placentas (P < .05). However, expression did not differ at term by disease state,
      compartment, or labor status. Siglec-6 was not detectable in maternal serum.
      Overexpression of Siglec-6 protein in preterm PE placentas may contribute to or
      represent a response to PE pathogenesis and suggests that preterm PE pathogenesis
      is distinct from term PE.

PMID- 23171685
TI  - Urinary follicle-stimulating hormone as a measure of natural fertility in a
      community cohort.
AB  - High serum follicle-stimulating hormone (FSH) levels have been associated with
      diminished ovarian reserve; however, the association between high urinary FSH and
      reduced natural fertility has yet to be established. We sought to characterize
      the relationship between a single or multiple measurements of early follicular
      phase urinary FSH and fertility. Women (n = 209), 30 to 44 years old with no
      history of infertility, who had been trying to conceive for less than 3 months,
      provided early follicular phase urine. Participants subsequently kept a diary to
      record bleeding and intercourse and conducted standardized pregnancy testing for
      up to 6 months. A subset of women (N = 95) collected urine on cycle day 3 for up
      to 6 cycles. Urine was analyzed for FSH and creatinine (cr) corrected.
      Proportional hazard models were used to calculate fecundability ratios (FRs).
      Urinary FSH levels across cycles from the same woman were highly correlated
      (adjusted intraclass correlation = .77); within-woman variance was 3-fold lower
      than variance among women. Women with an initial urinary FSH level <7 mIU/mg cr
      exhibited a nonsignificant reduction in the probability of pregnancy (adjusted FR
      0.71, 95% confidence interval [CI]: 0.45-1.13), as did women with elevated
      urinary FSH (>=12 mIU/mg cr; adjusted FR 0.78, 95% CI: 0.46-1.32). Using the most
      recent or maximum urinary FSH value did not strengthen the association. In the
      general population, urinary FSH levels appear to be nonlinearly associated with
      fertility; however, broad CIs indicate a lack of statistical significance.
      Repetitive testing appears to be of little benefit.

PMID- 23171686
TI  - Increased circulating MMP-2 levels in infertile patients with moderate and severe
      pelvic endometriosis.
AB  - The current study compares the levels of matrix metalloproteinase (MMP)-2 and MMP
      9 in the follicular fluid (FF) of infertile patients with and without
      endometriosis submitted to ovarian stimulation for in vitro fertilization and the
      levels of MMP-2 in the serum of the same patients. We also evaluated whether the
      severity of endometriosis can influence serum and/or FF concentration of these
      metalloproteinases. A cross-sectional study was conducted on 30 patients: stage
      I/II endometriosis (n = 10), stage III/IV endometriosis (n = 10), and control
      (infertility due to tubal and/or male factor; n = 10). Blood samples for the
      analysis of MMP-2 levels were obtained during the early follicular phase of the
      menstrual cycle. The FF samples for the analysis of MMP-2 and MMP-9 were obtained
      on the day of oocyte retrieval. The concentrations of MMP-2 and MMP-9 were
      determined by zymography. No intragroup or intergroup difference was observed in
      MMP-2 or MMP-9 levels in FF. Significantly higher MMP-2 levels were detected in
      the serum of infertile women with stage III/IV endometriosis compared to women
      with stage I/II endometriosis. In conclusion, no differences were observed in the
      follicular levels of MMP-2 and MMP-9 between infertile patients with and without
      endometriosis. However, the levels of MMP-2 were significantly higher in the
      serum of infertile women with advanced stages of endometriosis. Taken together,
      the present results demonstrate that advanced pelvic endometriosis severity is
      related to higher serum MMP-2 levels but does not influence follicular MMP-2 or
      MMP-9 levels in periovulatory follicles obtained from stimulated cycles.

PMID- 23171687
TI  - Consumption of ultra-processed foods and likely impact on human health. Evidence
      from Canada.
AB  - OBJECTIVE: To investigate consumption of ultra-processed products in Canada and
      to assess their association with dietary quality. DESIGN: Application of a
      classification of foodstuffs based on the nature, extent and purpose of food
      processing to data from a national household food budget survey. Foods are
      classified as unprocessed/minimally processed foods (Group 1), processed culinary
      ingredients (Group 2) or ultra-processed products (Group 3). SETTING: All
      provinces and territories of Canada, 2001. SUBJECTS: Households (n 5643).
      RESULTS: Food purchases provided a mean per capita energy availability of 8908
      (se 81) kJ/d (2129 (se 19) kcal/d). Over 61.7 % of dietary energy came from ultra
      processed products (Group 3), 25.6 % from Group 1 and 12.7 % from Group 2. The
      overall diet exceeded WHO upper limits for fat, saturated fat, free sugars and Na
      density, with less fibre than recommended. It also exceeded the average energy
      density target of the World Cancer Research Fund/American Institute for Cancer
      Research. Group 3 products taken together are more fatty, sugary, salty and
      energy-dense than a combination of Group 1 and Group 2 items. Only the 20 %
      lowest consumers of ultra-processed products (who consumed 33.2 % of energy from
      these products) were anywhere near reaching all nutrient goals for the prevention
      of obesity and chronic non-communicable diseases. CONCLUSIONS: The 2001 Canadian
      diet was dominated by ultra-processed products. As a group, these products are
      unhealthy. The present analysis indicates that any substantial improvement of the
      diet would involve much lower consumption of ultra-processed products and much
      higher consumption of meals and dishes prepared from minimally processed foods
      and processed culinary ingredients.

PMID- 23171688
TI  - Clostridium difficile isolated from the fecal contents of swine in Japan.
AB  - A total of 250 fecal content samples were collected from 25 farrow-to-finish pig
      farms and examined for the prevalence of Clostridium difficile by using ethanol
      treatment followed by plating onto selective media--cycloserine-cefoxitin
      mannitol agar--for the isolation of Clostridium difficile. Two specimens (0.8%,
      95% confidential interval: 0-2.9%) were positive for C. difficile. One isolate
      was only positive for toxin B, and the other isolate was negative for both toxins
      A and B. Thus, prevalence of Clostridium difficile was found to be low among
      finishing pigs in Japan.

PMID- 23171689
TI  - L-type amino acid transporter 1 (LAT1) expression in canine mammary gland tumors.
AB  - L-type amino acid transporter 1 (LAT1), an isoform of amino acid transport system
      L, transports branched or aromatic amino acids essential for fundamental cellular
      activities such as cellular growth, proliferation and maintenance. This amino
      acid transporter recently has received attention because of its preferential and
      up-regulated expression in a variety of human tumors, in contrast to its limited
      distribution and low-level expression in normal tissues. In this study, to
      explore the feasibility of using LAT1 expression as a molecular marker in mammary
      gland tumors (MGT), we performed a comparative study of LAT1 expression at the
      mRNA and protein levels in normal mammary gland cells and tumor cells.
      Conventional RT-PCR and Western blotting were performed on MGT tissues from 16
      dogs and normal organs from nine healthy dogs. LAT1 expression was detected in
      ten of the 16 MGT patients. As is the case in human tissues, LAT1 showed limited
      expressional distribution in normal canine organs. For quantitative expressional
      comparison, extensive real-time RT-PCR was performed on mRNA samples from 53 MGT
      patients. The comparison demonstrated that LAT1 mRNA levels from MGT tissues were
      20 times higher than those in normal mammary gland tissues. Additionally,
      histologically invasive MGT showed a higher expression of LAT1 than non-invasive
      tumors. These findings suggest that LAT1 could be a clinical marker and
      therapeutic target for invasive malignant MGT.

PMID- 23171690
TI  - Colocalization of nitric oxide synthase, vasoactive intestinal polypeptide and
      tyrosine hydroxylase immunoreactivities in postganglionic neurons of the quail
      superior cervical ganglion.
AB  - The colocalization of immunoreactivity to nitric oxide synthase (NOS), vasoactive
      intestinal polypeptide (VIP) and tyrosine hydroxylase (TH) in the superior
      cervical ganglion (SCG) was investigated in the quail. In this bird, a
      substantial amount of NOS-immunoreactive (IR) cells were consistently found in
      the SCG without colchicine treatment or nerve ligation. The finding worthy of
      pointing out was that three-fourths of these NOS-IR cells were positive for TH.
      VIP-IR cells appeared with markedly low frequency than NOS-IR cells. They were
      generally small in size and often located in the ganglion peripheral. There were
      no VIP-IR cells positive for TH or negative for NOS: VIP immunoreactivity always
      appears in NOS-IR cells negative for TH. Thus, the results of the present study
      clearly showed the existence of two distinct subpopulations of postganglionic NOS
      IR neurons (one is catecholaminergic and negative for VIP, and the other is non
      catecholaminergic and positive for VIP). This suggests that nitric oxide (NO) and
      possibly VIP act as postganglionic neurotransmitters or neuromodulators in the
      quail SCG. The predominant appearance of the former category of NOS-IR cells must
      be considered in relation to some specific NO-induced controlling mechanisms of
      SCG neurons.

PMID- 23171691
TI  - Rediscovery of Haematobosca zuluensis (Zumpt), (Diptera, Stomoxyinae): re
      description and amended keys for the genus.
AB  - BACKGROUND: Prior to this publication, the biting fly Haematobosca zuluensis
      (Zumpt, 1950) (Diptera, Muscidae, Stomoxyinae) was known only from a single male
      specimen collected in 1923 in Zululand, South Africa. Seven additional males were
      subsequently captured in the Kruger National Park of South Africa, one in 1984
      and six in 1991, but remained unidentified until now. The genus includes species
      of considerable veterinary significance, but current keys for identification of
      species are misleading due to inadequate description of H. zuluensis. METHODS:
      External morphological features are described to enable species characterization,
      including intraspecific variability. RESULTS: This paper confirms the existence
      of H. zuluensis, expands its known range, provides a full description of males of
      the species, and gives an up to date set of keys for the 15 known species within
      the genus. Available records suggest that Haematobosca zuluensis is a low density
      species as yet known only from wildlife areas of South Africa. CONCLUSIONS: The
      additional specimens of H. zuluensis have enabled an improved description of the
      species and an improved set of keys to identify constituent members of the genus.

PMID- 23171692
TI  - Connexin 26 and 30 mutations in paediatric patients with congenital, non
      syndromic hearing loss treated with cochlear implantation in Mediterranean
      Turkey.
AB  - OBJECTIVE: Mutations in the genes for connexin 26 (GJB2) and connexin 30 (GJB6)
      play an important role in autosomal recessive, non-syndromic hearing loss. This
      study aimed to detect the 35delG and 167delT mutations of the GJB2 gene and the
      del(GJB6-D13S1830) mutation of the GJB6 gene in paediatric patients diagnosed
      with congenital, non-syndromic hearing loss and treated with cochlear
      implantation in Mediterranean Turkey. MATERIALS AND METHOD: We included 94
      children diagnosed with congenital, non-syndromic hearing loss and treated with
      cochlear implantation. Blood samples were collected, DNA extracted and an enzyme
      linked immunosorbent assay performed to enable molecular diagnosis of mutations.
      RESULTS: Of the 94 children analysed, the 35delG mutation was detected in 12
      (12.7 per cent): 10 (83.3 per cent) were homozygous and 2 (16.7 per cent)
      heterozygous mutant. The 167delT and del(GJB6-D13S1830) mutations were not
      detected. CONCLUSION: The GJB2-35delG mutation is a major cause of congenital,
      non-syndromic hearing loss in this study population.

PMID- 23171693
TI  - Antimicrobial drug-resistant Escherichia coli in wild birds and free-range
      poultry, Bangladesh.
AB  - Multidrug resistance was found in 22.7% of Escherichia coli isolates from bird
      samples in Bangladesh; 30% produced extended-spectrum beta-lactamases, including
      clones of CTX-M genes among wild and domestic birds. Unrestricted use of
      antimicrobial drugs in feed for domestic birds and the spread of resistance genes
      to the large bird reservoir in Bangladesh are growing problems.

PMID- 23171694
TI  - The polyketide synthase-associated multidrug tolerance in Mycobacterium
      intracellulare clinical isolates.
AB  - BACKGROUND: Intrinsic multidrug resistance of the Mycobacterium avium
      intracellulare complex presents a serious problem in the treatment of the
      diseases caused by these bacteria. Recently, it was shown that deletion of a
      polyketide synthase, Pks12, in an M. avium laboratory strain decreases this
      intrinsic resistance. METHODS: We investigated Pks12 expression and its enzymatic
      activity in 9 clinical isolates of M. intracellulare, and compared their drug
      susceptibilities to 4 drugs. Also, we made pks12-disrupted M. bovis bacillus
      Calmette-Guerin (BCG) mutant and its complemented strain. Using these BCG and M.
      intracellulare strains, we observed intracellular accumulation of ethidium
      bromide (EtBr). RESULTS: We found positive correlations between Pks12 and drug
      resistance for all of the antibiotics tested. The drug susceptible M.
      intracellulare strain showed higher EtBr accumulation. Consistent with this, EtBr
      was much more accumulated in pks12-disrupted BCG than wild-type or the
      complemented strains. CONCLUSIONS: Collectively, these results suggest that Pks12
      controls the multidrug resistance in part through intracellular drug
      accumulation.

PMID- 23171695
TI  - Mood-congruent amygdala responses to subliminally presented facial expressions in
      major depression: associations with anhedonia.
AB  - BACKGROUND: Anhedonia has long been recognized as a key feature of major
      depressive disorders, but little is known about the association between hedonic
      symptoms and neurobiological processes in depressed patients. We investigated
      whether amygdala mood-congruent responses to emotional stimuli in depressed
      patients are correlated with anhedonic symptoms at automatic levels of
      processing. METHODS: We measured amygdala responsiveness to subliminally
      presented sad and happy facial expressions in depressed patients and matched
      healthy controls using functional magnetic resonance imaging. Amygdala
      responsiveness was compared between patients and healthy controls within a 2
      (group) x 2 (emotion) design. In addition, we correlated patients' amygdala
      responsiveness to sad and happy facial stimuli with self-report questionnaire
      measures of anhedonia. RESULTS: We included 35 patients and 35 controls in our
      study. As in previous studies, we observed a strong emotion x group interaction
      in the bilateral amygdala: depressed patients showed greater amygdala responses
      to sad than happy faces, whereas healthy controls responded more strongly to
      happy than sad faces. The lack of automatic right amygdala responsiveness to
      happy faces in depressed patients was associated with higher physical anhedonia
      scores. LIMITATIONS: Almost all depressed patients were taking antidepressant
      medications. CONCLUSION: We replicated our previous finding of depressed patients
      showing automatic amygdala mood-congruent biases in terms of enhanced reactivity
      to negative emotional stimuli and reduced activity to positive emotional stimuli.
      The altered amygdala processing of positive stimuli in patients was associated
      with anhedonia scores. The results indicate that reduced amygdala responsiveness
      to positive stimuli may contribute to anhedonic symptoms due to
      reduced/inappropriate salience attribution to positive information at very early
      processing levels.

PMID- 23171696
TI  - Single treatments that have lasting effects: some thoughts on the antidepressant
      effects of ketamine and botulinum toxin and the anxiolytic effect of psilocybin.
AB  - Recent clinical trials suggest that 3 single biological treatments have effects
      that persist. Based on research showing that the muscles involved in facial
      expressions can feed back to influence mood, a single trial diminishing glabella
      frown lines with botulinum toxin demonstrated a significant antidepressant effect
      for 16 weeks. Based primarily on research with animal models of depression
      suggesting that glutamate may be involved in depression, the N-methyl-D-aspartate
      antagonist ketamine has been tested in several trials. A single dose decreased
      depression for up to a week. The reported effects of the use of mushrooms
      containing psilocybin by a number of cultures around the world has stimulated
      several trials showing beneficial effects of a single dose of psilocybin for over
      a year in healthy people, and for up to 3 months in patients with anxiety
      disorders who have advanced cancer. This article discusses these studies, their
      rationale, their possible mechanisms of action, the future clinical research
      required to establish these therapies and the basic research required to optimize
      single treatments that have lasting effects.

PMID- 23171697
TI  - Multiphysics model of a rat ventricular myocyte: a voltage-clamp study.
AB  - BACKGROUND: The objective of this study is to develop a comprehensive model of
      the electromechanical behavior of the rat ventricular myocyte to investigate the
      various factors influencing its contractile response. METHODS: Here, we couple a
      model of Ca2 + dynamics described in our previous work, with a well-known model
      of contractile mechanics developed by Rice, Wang, Bers and de Tombe to develop a
      composite multiphysics model of excitation-contraction coupling. This
      comprehensive cell model is studied under voltage clamp (VC) conditions, since it
      allows to focus our study on the elaborate Ca2 + signaling system that controls
      the contractile mechanism. RESULTS: We examine the role of various factors
      influencing cellular contractile response. In particular, direct factors such as
      the amount of activator Ca2 + available to trigger contraction and the type of
      mechanical load applied (resulting in isosarcometric, isometric or unloaded
      contraction) are investigated. We also study the impact of temperature (22 to 38
      degrees C) on myofilament contractile response. The critical role of myofilament
      Ca2 + sensitivity in modulating developed force is likewise studied, as is the
      indirect coupling of intracellular contractile mechanism with the plasma membrane
      via the Na + /Ca2 + exchanger (NCX). Finally, we demonstrate a key linear
      relationship between the rate of contraction and relaxation, which is shown here
      to be intrinsically coupled over the full range of physiological perturbations.
      CONCLUSIONS: Extensive testing of the composite model elucidates the importance
      of various direct and indirect modulatory influences on cellular twitch response
      with wide agreement with measured data on all accounts. Thus, the model provides
      mechanistic insights into whole-cell responses to a wide variety of testing
      approaches used in studies of cardiac myofilament contractility that have
      appeared in the literature over the past several decades.

PMID- 23171698
TI  - Early results after surgical treatment of left ventricular aneurysm.
AB  - BACKGROUND: Left ventricular aneurysm (LVA) is a serious complication of
      myocardial infarction and reduces the chances of survival. Controversy still
      exists regarding the optimal surgical technique for LVA repair. We analyze the
      efficacy of two techniques, linear vs. endoventricular circular patch plasty, for
      repair of LVA and the efficacy of surgical ventricular restoration (SVR) on
      beating heart. METHODS: This study included 62 patients who underwent SVR from
      1086 consecutive patients were subjected to coronary artery bypass grafting
      (CABG) between 2000 and 2009. All selected patients were divided either into
      group liner or patch according to the choice of the repair technique depended on
      factors such as localization, size and dimension of the scar. The patients also
      were divided either into group beating heart or cardioplegia. The pre-, intra-
      and postoperative relevant data of all selected patients were analyzed. RESULTS:
      The mortality was not significantly different between linear and patch repair
      groups, also the actuarial survival rates within 24 months (p= 0.529).
      Postoperative echocardiographic findings showed significant improvements in left
      ventricular function in both groups. The beating heart technique reduced
      postoperative peak release by 27% for Cardiac troponin I (cTnI) compared with the
      cardioplegia group (0.46 +/- 0.06 ng/mL versus 0.63 +/- 0.09 ng/mL, p= 0.004),
      and increased the perioperative survival by 9% (97.2% versus 88.5%), but the
      actuarial survival rates were not significantly different between the groups from
      2 to 24 months (p= 0.151). CONCLUSIONS: Both techniques (linear and patch)
      achieved good results with respect to mortality, functional status and survival.
      The choice of surgical technique should be adapted in each patient. The beating
      heart technique may to some extent relieve myocardial injury in patients
      undergoing SVR.

PMID- 23171699
TI  - Clinical review: Circulatory shock--an update: a tribute to Professor Max Harry
      Weil.
AB  - Circulatory shock is common and associated with high morbidity and mortality.
      Appropriate shock treatment relies on a good understanding of the
      pathophysiological mechanisms underlying shock. In this article, we provide an
      update on the description, classification, and management of shock states built
      on foundations laid by Dr Max Harry Weil, a key early contributor to this field. 

PMID- 23171700
TI  - Diagnostic assays for Crimean-Congo hemorrhagic fever.
AB  - Crimean-Congo hemorrhagic fever (CCHF) is a highly contagious viral tick-borne
      disease with case-fatality rates as high as 50%. We describe a collaborative
      evaluation of the characteristics, performance, and on-site applicability of
      serologic and molecular assays for diagnosis of CCHF. We evaluated ELISA,
      immunofluorescence, quantitative reverse transcription PCR, and low-density
      macroarray assays for detection of CCHF virus using precharacterized archived
      patient serum samples. Compared with results of local, in-house methods, test
      sensitivities were 87.8%-93.9% for IgM serology, 80.4%-86.1% for IgG serology,
      and 79.6%-83.3% for genome detection. Specificity was excellent for all assays;
      molecular test results were influenced by patient country of origin. Our findings
      demonstrate that well-characterized, reliable tools are available for CCHF
      diagnosis and surveillance. The on-site use of such assays by health laboratories
      would greatly diminish the time, costs, and risks posed by the handling,
      packaging, and shipping of highly infectious biologic material.

PMID- 23171701
TI  - Laparoscopic pyeloplasty: a comparison between the transperitoneal and
      retroperitoneal approach during the learning curve.
AB  - PURPOSE: To compare the transperitoneal and the retroperitoneal approach in the
      laparoscopic management of pelviureteric junction (PUJ) obstruction, and to find
      out which approach is preferable during the learning curve period at two
      different urologic centers. MATERIALS AND METHODS: We retrospectively evaluated
      50 consecutive laparoscopic pyeloplasties performed by two urologists from
      different urologic centers during their learning curve period in laparoscopy.
      Each surgeon used a different approach: transperitoneal (group A) or
      retroperitoneal (group B). Timing for patient positioning, access to the
      operating field, ureter and PUJ isolation, PUJ suturing, total time of the
      surgery procedure and blood loss were recorded to compare the transperitoneal
      with the retroperitoneal approach. Intraoperative complications and perioperative
      morbidity were also reported. RESULTS: 22 procedures were performed using the
      transperitoneal method (group A) and 28 using the retroperitoneal method (group
      B). Significant differences between groups A and B were observed in terms of time
      for access to the operating field (mean 25 and 15 min, respectively, p < 0.05),
      time for suturing the PUJ (mean 57 and 103 min, respectively, p < 0.001), and
      total operative time (mean 127 and 201 min, respectively, p < 0.002). No
      statistical differences were observed for any other parameters. Average follow-up
      was 10 and 11 months for groups A and B; no statistical differences were
      observed. CONCLUSIONS: We suggest that young urologists during the learning curve
      for laparoscopy should perform laparoscopic pyeloplasty using a transperitoneal
      route. In expert hands, both transperitoneal and retroperitoneal approaches are
      feasible, and the choice depends on personal preference.

PMID- 23171702
TI  - Centrosome fine ultrastructure of the osteocyte mechanosensitive primary cilium.
AB  - The centrosome is the principal microtubule organization center in cells, giving
      rise to microtubule-based organelles (e.g., cilia, flagella). The aim was to
      study the osteocyte centrosome morphology at an ultrastructural level in relation
      to its mechanosensitive function. Osteocyte centrosomes and cilia in tibial
      cortical bone were explored by acetylated alpha-tubulin (AalphaTub)
      immunostaining under confocal microscopy. For the first time, fine ultrastructure
      and spatial orientation of the osteocyte centrosome were explored by transmission
      electron microscopy on serial ultrathin sections. AalphaTub-positive staining was
      observed in 94% of the osteocytes examined (222/236). The mother centriole formed
      a short primary cilium and was longer than the daughter centriole due to an
      intermediate zone between centriole and cilium. The proximal end of the mother
      centriole was connected with the surface of daughter centriole by striated
      rootlets. The mother centriole exhibited distal appendages that interacted with
      the cell membrane and formed a particular structure called "cilium membrane
      prolongation." The primary cilium was mainly oriented perpendicular to the long
      axis of bone. Mother and daughter centrioles change their original mutual
      orientation during the osteocyte differentiation process. The short primary
      cilium is hypothesized as a novel type of fluid-sensing organelle in osteocytes.

PMID- 23171703
TI  - Assessment of pre- and postoperative endocrine function in 94 patients with
      Rathke's cleft cyst.
AB  - We reviewed 94 patients with Rathke's cleft cyst (RCC) who were surgically
      treated at Nippon Medical School Hospital between December 1995 and July 2009 to
      clarify the effect of surgery on their endocrine function. In our statistical
      analysis we considered their age and sex, the cyst volume, and preoperative MRI
      findings. Using simple linear- and multiple regression analysis we evaluated the
      association between these factors and their preoperative hormone baseline levels.
      To assess pre- and postoperative anterior pituitary function we subjected the
      results of various hormone loading tests to the Wilcoxon rank sum test. Surgery
      improved headache and visual impairment in most patients and elevated PRL levels
      were significantly normalized after surgery (p = 0.004). However, pre- and
      postoperative anterior pituitary hormone loading tests revealed that the levels
      of GH, TSH, LH, and FSH were not improved significantly by surgery. Although the
      ACTH loading test showed postoperative improvement, the change was not
      statistically significant. We suggest that RCC patients with headache or visual
      impairment are good candidates for surgery. We also recommend that patients with
      hyperprolactinemia and those with ACTH deficiency whose MRI findings reveal low
      intensity on T1WI and high-intensity on T2WI are likely to benefit from surgery.
      In contrast, RCC patients with other hormone dysfunctions do not appear to
      benefit from surgical intervention.

PMID- 23171704
TI  - Evaluation of the diagnostic criteria for Cushing's disease in Japan.
AB  - Adrenocorticotropic hormone (ACTH)-dependent Cushing's syndrome is caused by an
      ACTH-producing tumor, as is the case with Cushing's disease and ectopic ACTH
      syndrome (EAS). Diagnosis and differential diagnosis of Cushing's disease from
      EAS in ACTH-dependent Cushing's syndrome are thus challenging problems in
      clinical endocrinology. The diagnostic criteria for Cushing's disease in Japan,
      established by the working group of the Japan Ministry of Health, Labour and
      Welfare, were originally reported in 2003 and revised in 2007 and 2010. In
      addition, criteria for subclinical Cushing's disease were established in Japan in
      2010. In this review, we evaluate the usefulness and accuracy of the most recent
      diagnostic criteria. Previous data suggest that as an initial test of Cushing's
      syndrome, 0.5 mg dexamethasone is more sensitive than 1 mg in the overnight
      dexamethasone suppression test (DST). Here, we recommend 0.5 mg plus a plasma
      cortisol cut-off level of 3 ug/dL as a suitable low-dose overnight DST for
      screening of all cases of ACTH-dependent Cushing's syndrome in Japan. Recently,
      standardization of cortisol measurements by the ID-LC/MS/MS method using seven
      assay kits with standard plasma material containing synthetic hydrocortisone-d4
      was carried out in Japan. The resulting relative standard deviation was within
      10%. The cut-off value remains valid even after standardization of plasma
      cortisol measurements. Although the recent diagnostic criteria achieve higher
      diagnostic specificity, care should be taken since data for Cushing's disease
      partially overlaps with some cases of EAS. Overall, therefore, this review
      suggests that the accuracy of each diagnostic test should be considered.

PMID- 23171705
TI  - Melatonin as a free radical scavenger in the ovarian follicle.
AB  - This review summarizes new findings related to beneficial effects of melatonin 
      (N-acetyl-5-methoxytryptamine) on reproductive physiology.  Recently many
      researchers have begun to study the local role of melatonin as an antioxidant. 
      We focused on intra-follicular role of melatonin in the ovary.  Melatonin,
      secreted by the pineal gland, is taken up into the follicular fluid from the
      blood.  Reactive oxygen species (ROS) are produced within the follicles, during
      the ovulatory process.  Melatonin reduces oxidative stress as an antioxidant, and
      contribute to oocyte maturation, embryo development and luteinization of
      granulosa cells.  Our clinical study demonstrated that melatonin treatment for
      infertile women increases intra-follicular melatonin concentrations, reduces
      intra-follicular oxidative damage, and elevates fertilization and pregnancy
      rates.  Melatonin treatment also improves progesterone production by corpus
      luteum in infertile women with luteal phase defect.  Melatonin treatment could
      become a new cure for improving oocyte quality and luteal function in infertile
      women.

PMID- 23171706
TI  - Inhibition of insulin secretion from rat pancreatic islets by dexmedetomidine and
      medetomidine, two sedatives frequently used in clinical settings.
AB  - The aim of this study was to determine whether dexmedetomidine (DEX) and
      medetomidine (MED), alpha2-adrenergic agonists clinically used as sedatives,
      influence insulin secretion from rat pancreatic islets. Islets were isolated from
      adult male Wistar rats after collagenase digestion. Static incubation was used to
      determine effects of DEX or MED on insulin secretion and ionic-channel currents
      of beta-cells. Results indicate that both drugs dose-dependently inhibit insulin
      secretion, DEX more potently than MED. The inhibitory effects were attenuated by
      addition of yohimbine or by pretreatment of rats with pertussis toxin (PTX). 10
      nM DEX decreased the current amplitude of voltage-dependent Ca2+ channels, but
      this did not occur when the N-type Ca2+ channel blocker omega-conotoxin was
      added. In the presence of tetraethylammonium, a classical voltage-gated K+
      channel (Kv channel) blocker, the magnitude of inhibition of insulin secretion by
      MED was reduced. However, when tolbutamide, a specific blocker of the ATP
      sensitive K+ channel (KATP channel), was present, the magnitude of MED inhibition
      of insulin secretion was not influenced, suggesting that Kv-channel activity
      alteration, but not that of KATP channels, is involved in MED-associated insulin
      secretory inhibition. The Kv-channel currents were increased during 1 nM MED
      exposure at membrane potentials ranging from -30 mV to -10 mV, where action
      potentials were generated in response to glucose stimulation. These results
      indicate that DEX and MED inhibit insulin secretion through an alpha2
      adrenoceptor and PTX-sensitive GTP-binding protein pathway that eventually
      involves Kv channel activation and Ca2+ channel inhibition.

PMID- 23171707
TI  - Westward spread of Echinococcus multilocularis in foxes, France, 2005-2010.
AB  - During 2005-2010, we investigated Echinococcus multilocularis infection within
      fox populations in a large area in France. The parasite is much more widely
      distributed than hitherto thought, spreading west, with a much higher prevalence
      than previously reported. The parasite also is present in the large conurbation
      of Paris.

PMID- 23171708
TI  - Abundance of Ixodes ricinus and prevalence of Borrelia burgdorferi s.l. in the
      nature reserve Siebengebirge, Germany, in comparison to three former studies from
      1978 onwards.
AB  - BACKGROUND: During the last decades, population densities of Ixodes ricinus and
      prevalences of Borrelia burgdorferi s.l. have increased in different regions in
      Europe. In the present study, we determined tick abundance and the prevalence of
      different Borrelia genospecies in ticks from three sites in the Siebengebirge,
      Germany, which were already examined in the years 1987, 1989, 2001 and 2003. Data
      from all investigations were compared. METHODS: In 2007 and 2008, host-seeking I.
      ricinus were collected by monthly blanket dragging at three distinct vegetation
      sites in the Siebengebirge, a nature reserve and a well visited local recreation
      area near Bonn, Germany. In both years, 702 ticks were tested for B. burgdorferi
      s.l. DNA by nested PCR, and 249 tick samples positive for Borrelia were further
      genotyped by reverse line blotting. RESULTS: A total of 1046 and 1591 I. ricinus
      were collected in 2007 and 2008, respectively. In comparison to previous studies
      at these sites, the densities at all sites increased from 1987/89 and/or from
      2003 until 2008. Tick densities and Borrelia prevalences in 2007 and 2008,
      respectively, were not correlated for all sites and both years. Overall, Borrelia
      prevalence of all ticks decreased significantly from 2007 (19.5%) to 2008
      (16.5%), thus reaching the same level as in 2001 two times higher than in 1987/89
      (7.6%). Since 2001, single infections with a Borrelia genospecies predominated in
      all collections, but the number of multiple infections increased, and in 2007,
      for the first time, triple Borrelia infections occurred. Prevalences of Borrelia
      genospecies differed considerably between the three sites, but B. garinii or B.
      afzelii were always the most dominant genospecies. B. lusitaniae was detected for
      the first time in the Siebengebirge, also in co-infections with B. garinii or B.
      valaisiana. CONCLUSIONS: Over the last two centuries tick densities have changed
      in the Siebengebirge at sites that remained unchanged by human activity since
      they belong to a nature reserve. Abiotic and biotic conditions most likely
      favored the host-seeking activity of I. ricinus and the increase of multiple
      Borrelia infections in ticks. These changes have led to a potential higher risk
      of humans and animals to be infected with Lyme borreliosis.

PMID- 23171710
TI  - Beware of non-ulceroglandular tularaemia cases in your area.

PMID- 23171709
TI  - Determinants of male involvement in maternal and child health services in sub
      Saharan Africa: a review.
AB  - INTRODUCTION: Male participation is a crucial component in the optimization of
      Maternal and Child Health (MCH) services. This is especially so where prevention
      strategies to decrease Mother-to-Child Transmission (MTCT) of Human
      Immunodeficiency Virus (HIV) are sought. This study aims to identify determinants
      of male partners' involvement in MCH activities, focusing specifically on HIV
      prevention of maternal to child transmission (PMTCT) in sub-Saharan Africa.
      METHODS: Literature review was conducted using the following data bases:
      Pubmed/MEDLINE; CINAHL; EMBASE; COCHRANE; Psych INFORMATION and the websites of
      the International AIDS Society (IAS), the International AIDS Conference and the
      International Conference on AIDS in Africa (ICASA) 2011. RESULTS: We included 34
      studies in this review, which reported on male participation in MCH and PMTCT
      services. The majority of studies defined male participation as male involvement
      solely during antenatal HIV testing. Other studies defined male involvement as
      any male participation in HIV couple counseling. We identified three main
      determinants for male participation in PMTCT services: 1) Socio-demographic
      factors such as level of education, income status; 2) health services related
      factors such as opening hours of services, behavior of health providers and the
      lack of space to accommodate male partners; and 3) Sociologic factors such as
      beliefs, attitudes and communication between men and women. CONCLUSION: There are
      many challenges to increase male involvement/participation in PMTCT services. So
      far, few interventions addressing these challenges have been evaluated and
      reported. It is clear however that improvement of antenatal care services by
      making them more male friendly, and health education campaigns to change beliefs
      and attitudes of men are absolutely needed.

PMID- 23171711
TI  - Acute kidney injury requiring dialysis following carmustine and etoposide during
      autologous stem cell transplantation.
AB  - BACKGROUND: The Stanford BCNU protocol (carmustine, etoposide and
      cyclophosphamide) is a high-dose conditioning regimen widely used prior to
      autologous stem cell transplantation. While acute renal failure requiring renal
      replacement therapy is a known but rare complication of autologous stem cell
      transplantation, acute nephrotoxicity following carmustine and etoposide has not
      yet been reported. CASE: We present the first case of carmustine-induced acute
      kidney injury in the setting of autologous stem cell transplantation and perform
      a review of the literature. Renal failure was associated with a sharp rise in
      serum creatinine, oliguria and trace proteinuria. Urgent haemodialysis was
      required; however, renal failure resolved after 7 days. CONCLUSION: Although a
      rare complication, its severity mandates close monitoring of renal function as
      early recognition and treatment may limit long-term sequelae.

PMID- 23171713
TI  - Systematic review of head cooling in adults after traumatic brain injury and
      stroke.
AB  - BACKGROUND: Brain injuries resulting from trauma and stroke are common and
      costly. Cooling therapy may reduce damage and potentially improve outcome. Head
      cooling targets the site of injury and may have fewer side effects than systemic
      cooling, but there has been no systematic review and the evidence base is
      unclear. OBJECTIVE: To assess the effect of non-invasive head cooling after
      traumatic brain injury (TBI) and stroke on intracranial and/or core body
      temperature, functional outcome and mortality, determine adverse effects and
      evaluate cost-effectiveness. REVIEW METHODS: Search strategy Major international
      databases [including MEDLINE, EMBASE, Cumulative Index to Nursing and Allied
      Health Literature, Web of Science, the British Library's Electronic Table of
      Contents (Zetoc)], The Cochrane Library, trial registers, country-specific
      databases (including China, Japan), Google Scholar, hypothermia conference
      reports and reference lists of papers were searched with no publication or
      language restrictions. The searches were conducted from March 2010 to April 2011,
      with no back date restriction. Selection criteria For formal analysis of effect
      of head cooling on functional outcome and mortality: randomised controlled trials
      (RCTs) of non-invasive head cooling in TBI or stroke in adults (aged >= 18
      years). RCT prespecified in protocol to include adequate randomisation and
      blinded outcome assessment. For assessment of effect on temperature and adverse
      effects of cooling methods/devices: studies of any type in TBI, stroke, cardiac
      arrest and neonatal hypoxic-ischaemic encephalopathy (adverse effects only). Data
      collection and analysis A study assessment and data collection form was developed
      and piloted. Data on functional outcome, mortality, temperature change and
      adverse effects of devices were sought and extracted. Two authors independently
      assessed RCTs for quality using the Cochrane Renal Group checklist. RESULTS: Out
      of 46 head-cooling studies in TBI and stroke, there were no RCTs of suitable
      quality for formal outcome analysis. Twelve studies had useable data on
      intracranial and core body temperature. These included 99 patients who were
      cooled after TBI or stroke and 198 patients cooled after cardiac arrest. The data
      were too heterogeneous for a single summary measure of effect (many studies had
      no measure of spread) and are therefore presented descriptively. The most
      effective techniques for which there were adequate data (nasal coolant and liquid
      cooling helmets) could reduce intracranial temperature by >= 1  degrees C in 1
      hour. The main device-related adverse effects were localised skin problems, which
      were generally mild and self-limiting. There were no suitable data for economic
      modelling, but an exploratory model of possible treatment effects and cost
      effectiveness of head cooling in TBI was created using local patient data.
      LIMITATIONS: We conducted extensive and sensitive searches but found no good
      quality RCTs of the effect of head cooling on functional outcome that met the
      review inclusion criteria. Most trials were small and/or of low methodological
      quality. However, if the trial reports did not reflect the true quality of the
      research, there may be some excluded trials that should have been included.
      Temperature data were often poorly reported which made it difficult to assess the
      effect of head cooling on temperature. CONCLUSIONS: Whether head cooling improves
      functional outcome or has benefits and fewer side effects compared with systemic
      cooling or no cooling could not be established. Some methods of head cooling can
      reduce intracranial temperature, which is an important first step in determining
      effectiveness, but there is insufficient evidence to recommend its use outside of
      research trials. The principal recommendations for research are that active
      cooling devices show the most promise for further investigation and more robust
      proof of concept of intracranial and core body temperature reduction with head
      cooling is required, clearly showing whether temperature has changed and by how
      much. FUNDING: The National Institute for Health Research Health Technology
      Assessment programme.

PMID- 23171712
TI  - Clinical review: Exogenous surfactant therapy for acute lung injury/acute
      respiratory distress syndrome--where do we go from here?
AB  - Acute lung injury and acute respiratory distress syndrome (ARDS) are
      characterised by severe hypoxemic respiratory failure and poor lung compliance.
      Despite advances in clinical management, morbidity and mortality remains high.
      Supportive measures including protective lung ventilation confer a survival
      advantage in patients with ARDS, but management is otherwise limited by the lack
      of effective pharmacological therapies. Surfactant dysfunction with quantitative
      and qualitative abnormalities of both phospholipids and proteins are
      characteristic of patients with ARDS. Exogenous surfactant replacement in animal
      models of ARDS and neonatal respiratory distress syndrome shows consistent
      improvements in gas exchange and survival. However, whilst some adult studies
      have shown improved oxygenation, no survival benefit has been demonstrated to
      date. This lack of clinical efficacy may be related to disease heterogeneity
      (where treatment responders may be obscured by nonresponders), limited
      understanding of surfactant biology in patients or an absence of therapeutic
      effect in this population. Crucially, the mechanism of lung injury in neonates is
      different from that in ARDS: surfactant inhibition by plasma constituents is a
      typical feature of ARDS, whereas the primary pathology in neonates is the
      deficiency of surfactant material due to reduced synthesis. Absence of phenotypic
      characterisation of patients, the lack of an ideal natural surfactant material
      with adequate surfactant proteins, coupled with uncertainty about optimal timing,
      dosing and delivery method are some of the limitations of published surfactant
      replacement clinical trials. Recent advances in stable isotope labelling of
      surfactant phospholipids coupled with analytical methods using electrospray
      ionisation mass spectrometry enable highly specific molecular assessment of
      phospholipid subclasses and synthetic rates that can be utilised for phenotypic
      characterisation and individualisation of exogenous surfactant replacement
      therapy. Exploring the clinical benefit of such an approach should be a priority
      for future ARDS research. 

PMID- 23171714
TI  - Borrelia, Rickettsia, and Ehrlichia species in bat ticks, France, 2010.
AB  - Argas vespertilionis, an argasid tick associated with bats and bat habitats in
      Europe, Africa, and Asia has been reported to bite humans; however, studies
      investigating the presence of vector-borne pathogens in these ticks are lacking.
      Using molecular tools, we tested 5 A. vespertilionis ticks collected in 2010 from
      the floor of a bat-infested attic in southwestern France that had been converted
      into bedrooms. Rickettsia sp. AvBat, a new genotype of spotted fever group
      rickettsiae, was detected and cultivated from 3 of the 5 ticks. A new species of
      the Ehrlichia canis group, Ehrlichia sp. AvBat, was also detected in 3 ticks.
      Four ticks were infected with Borrelia sp. CPB1, a relapsing fever agent of the
      Borrelia group that caused fatal borreliosis in a bat in the United Kingdom.
      Further studies are needed to characterize these new agents and determine if the
      A. vespertilionis tick is a vector and/or reservoir of these agents.

PMID- 23171715
TI  - Utility of an improved model of amyloid-beta (Abeta1-42) toxicity in
      Caenorhabditis elegans for drug screening for Alzheimer's disease.
AB  - BACKGROUND: The definitive indicator of Alzheimer's disease (AD) pathology is the
      profuse accumulation of amyloid-beta (Abeta) within the brain. Various in vitro
      and cell-based models have been proposed for high throughput drug screening for
      potential therapeutic benefit in diseases of protein misfolding. Caenorhabditis
      elegans offers a convenient in vivo system for examination of Abeta accumulation
      and toxicity in a complex multicellular organism. Ease of culturing and a short
      life cycle make this animal model well suited to rapid screening of candidate
      compounds. RESULTS: We have generated a new transgenic strain of C. elegans that
      expresses full length Abeta1-42. This strain differs from existing Abeta models
      that predominantly express amino-truncated Abeta3-42. The Abeta1-42 is expressed
      in body wall muscle cells, where it oligomerizes, aggregates and results in
      severe, and fully penetrant, age progressive-paralysis. The in vivo accumulation
      of Abeta1-42 also stains positive for amyloid dyes, consistent with in vivo
      fibril formation. The utility of this model for identification of potential
      protective compounds was examined using the investigational Alzheimer's
      therapeutic PBT2, shown to be neuroprotective in mouse models of AD and
      significantly improve cognition in AD patients. We observed that treatment with
      PBT2 provided rapid and significant protection against the Abeta-induced toxicity
      in C. elegans. CONCLUSION: This C. elegans model of full length Abeta1-42
      expression can now be adopted for use in screens to rapidly identify and assist
      in development of potential therapeutics and to study underlying toxic
      mechanism(s) of Abeta.

PMID- 23171716
TI  - Up-regulation of nicotinic acetylcholine receptors in menthol cigarette smokers.
AB  - One-third of smokers primarily use menthol cigarettes and usage of these
      cigarettes leads to elevated serum nicotine levels and more difficulty quitting
      in standard treatment programmes. Previous brain imaging studies demonstrate that
      smoking (without regard to cigarette type) leads to up-regulation of beta(2)*
      containing nicotinic acetylcholine receptors (nAChRs). We sought to determine if
      menthol cigarette usage results in greater nAChR up-regulation than non-menthol
      cigarette usage. Altogether, 114 participants (22 menthol cigarette smokers, 41
      non-menthol cigarette smokers and 51 non-smokers) underwent positron emission
      tomography scanning using the alpha(4)beta(2)* nAChR radioligand 2-[(18)F]fluoro
      A-85380 (2-FA). In comparing menthol to non-menthol cigarette smokers, an overall
      test of 2-FA total volume of distribution values revealed a significant between
      group difference, resulting from menthol smokers having 9-28% higher
      alpha(4)beta(2)* nAChR densities than non-menthol smokers across regions. In
      comparing the entire group of smokers to non-smokers, an overall test revealed a
      significant between-group difference, resulting from smokers having higher
      alpha(4)beta(2)* nAChR levels in all regions studied (36-42%) other than thalamus
      (3%). Study results demonstrate that menthol smokers have greater up-regulation
      of nAChRs than non-menthol smokers. This difference is presumably related to
      higher nicotine exposure in menthol smokers, although other mechanisms for
      menthol influencing receptor density are possible. These results provide
      additional information about the severity of menthol cigarette use and may help
      explain why these smokers have more trouble quitting in standard treatment
      programmes.

PMID- 23171717
TI  - Feasibility and safety of endoscopic submucosal dissection of esophageal or
      gastric carcinomas under general anesthesia.
AB  - OBJECTIVE: To investigate the feasibility and safety of endoscopic submucosal
      dissection (ESD) of esophageal or gastric carcinomas under general anesthesia.
      SUBJECTS AND METHODS: ESD removal of esophageal or gastric carcinomas was
      performed in 59 patients under midazolam sedation (control group), and in 46
      patients under general anesthesia (GA group). The procedural times, perioperative
      complications and patient's satisfaction with the procedures were recorded.
      RESULTS: There was no statistically significant difference in age (65 +/- 12 vs.
      58 +/- 11), male gender (43.5 vs. 49.2%), types or location or the size of the
      carcinomas (30 +/- 6 vs. 28 +/- 7 mm) between the control and GA groups (p >
      0.05). The mean procedural time in the GA group was shorter than in the control
      group (42.5 +/- 5.5 vs. 79.0 +/- 13.2 min, p = 0.01). The combined gastric
      perforation and postprocedural bleeding rate in the GA group was lower than in
      the control group, but the difference did not reach statistical significance (p =
      0.06). In the GA group, all patients rated the procedural experience as
      satisfactory, while in the control group, 38 (64.5%) rated the experience as
      satisfactory (p = 0.001). CONCLUSION: ESD under general anesthesia was associated
      with a shorter procedure time and a high rate of patient's satisfaction with the
      procedures.

PMID- 23171718
TI  - Current concepts in diagnosis and perioperative management of carcinoid heart
      disease.
AB  - Carcinoid tumors are neuroendocrine tumors with a very unpredictable clinical
      behavior. In the setting of hepatic metastases, the tumor's release of bioactive
      substances into the systemic circulation results in carcinoid syndrome: a
      constellation of symptoms among which cutaneous flushing, gastrointestinal
      hypermotility, and cardiac involvement are the most prominent. Cardiac
      manifestations, also known as carcinoid heart disease, are secondary to a severe
      fibrotic reaction which frequently involves the right-sided valves and may extend
      towards the subvalvular apparatus leading to valve thickening and retraction.
      Left-sided involvement is rare and mostly observed in the presence of an
      interatrial shunt, endobronchial tumor localization, and high tumor activity.
      Echocardiographic techniques often reveal noncoaptation of the valves, which are
      fixed in a semiopen position. In patients with advanced lesions and severe
      valvular dysfunction, surgery is currently the only definitive treatment to
      potentially improve quality of life and provide survival benefit. Although
      cardiac surgery has been traditionally reserved for those patients with
      symptomatic right ventricular failure, a significant trend towards improved
      surgical outcomes has triggered a more liberal referral for valve replacement.
      Carcinoid heart disease poses two distinct challenges for the anesthesiologist:
      carcinoid crisis and low cardiac output syndrome secondary to right ventricular
      failure. Carcinoid crisis, characterized by flushing, hypotension, and
      bronchospasm, may be precipitated by catecholamines and histamine releasing drugs
      used routinely in patients undergoing valve surgery. Although a broader
      utilization of octreotide have significantly simplified the anesthetic and
      perioperative management of these patients, a very balanced anesthetic technique
      is required to identify and manage low cardiac output syndrome. 

PMID- 23171719
TI  - Anesthesia for tracheobronchial surgery.
AB  - The airway is a crucial dynamic structure that spans different anatomical zones,
      including the intrathoracic, extrathoracic, tracheal, bronchial, and alveolar
      zones. Because of its vital role as the sole oxygen-conducting pathway to the
      alveoli, and hence to the human body, surgery involving any portion requires
      careful and specific planning by both the surgeon and the anesthesiologist. The
      review covers essential management points for proximal and distal tracheal
      procedures, including a discussion of tracheal stenting and tracheoplasty.

PMID- 23171720
TI  - Candidatus Neoehrlichia mikurensis in bank voles, France.
AB  - To further assess the geographic occurrence, possible vectors, and prevalence of
      Candidatus Neoehrlichia mikurensis, we analyzed spleen tissues from 276 voles
      trapped close to human settlements in France; 5 were infected with the organism.
      Sequencing showed the isolates carried the same genotype as the bacteria that
      caused disease in humans and animals elsewhere in Europe.

PMID- 23171721
TI  - The validation of a three-stage screening methodology for detecting active
      convulsive epilepsy in population-based studies in health and demographic
      surveillance systems.
AB  - BACKGROUND: There are few studies on the epidemiology of epilepsy in large
      populations in Low and Middle Income Countries (LMIC). Most studies in these
      regions use two-stage population-based screening surveys, which are time
      consuming and costly to implement in large populations required to generate
      accurate estimates. We examined the sensitivity and specificity of a three-stage
      cross-sectional screening methodology in detecting active convulsive epilepsy
      (ACE), which can be embedded within on-going census of demographic surveillance
      systems.We validated a three-stage cross-sectional screening methodology on a
      randomly selected sample of participants of a three-stage prevalence survey of
      epilepsy. Diagnosis of ACE by an experienced clinician was used as 'gold
      standard'. We further compared the expenditure of this method with the standard
      two-stage methodology. RESULTS: We screened 4442 subjects in the validation and
      identified 35 cases of ACE. Of these, 18 were identified as false negatives, most
      of whom (15/18) were missed in the first stage and a few (3/18) in the second
      stage of the three-stage screening. Overall, this methodology had a sensitivity
      of 48.6% and a specificity of 100%. It was 37% cheaper than a two-stage survey.
      CONCLUSION: This was the first study to evaluate the performance of a multi-stage
      screening methodology used to detect epilepsy in demographic surveillance sites.
      This method had poor sensitivity attributed mainly to stigma-related non-response
      in the first stage. This method needs to take into consideration the poor
      sensitivity and the savings in expenditure and time as well as validation in
      target populations. Our findings suggest the need for continued efforts to
      develop and improve case-ascertainment methods in population-based
      epidemiological studies of epilepsy in LMIC.

PMID- 23171722
TI  - Jet or intensive care unit ventilator during simulated percutaneous transtracheal
      ventilation: a lung model study.
AB  - BACKGROUND: Percutaneous transtracheal ventilation (PTV) via a jet ventilator
      (PTJV) is considered a rescue technique in difficult airway management. However,
      whether a conventional ventilator can generate adequate ventilation via PTV is
      not known. Our goal was to evaluate the tidal volume (V(T)) generated by a
      conventional ventilator during simulated PTV compared with PTJV in a lung model.
      METHODS: A lung model simulating an adult lung was used. A catheter was inserted
      through the artificial trachea and connected to either a jet ventilator or a
      conventional ventilator. The direction of catheter insertion was perpendicular to
      the trachea, pointing towards the lung and away from the lung. The jet ventilator
      was operated at 344.7 kPa. The conventional ventilator was operated in the
      pressure mode at peak inspiratory pressures of 40-90 cm H(2)O. RESULTS: The jet
      ventilator generated larger V(T) [817 (336) ml] when the catheter was pointing
      towards the lung than when pointing away from the lung or perpendicular to the
      trachea [121 (41) and 69 (24) ml, respectively, P<0.01]. With the conventional
      ventilator, changes in V(T) at different direction of catheter insertion were
      much less [222 (81) ml catheter pointing towards the lung, 229 (121) ml
      perpendicular to the trachea, and 187 (97) ml away from the lung]. CONCLUSIONS:
      Our result demonstrated that PTJV was effective only when the catheter was
      pointing towards the lung and requires high operating pressure. A conventional
      ventilator can generate reasonable minute ventilation through the transtracheal
      catheter less dependent on directions of catheter insertion and should be
      considered during emergent PTV.

PMID- 23171723
TI  - Association of ethnicity and acute kidney injury after cardiac surgery in a South
      East Asian population.
AB  - BACKGROUND: Postoperative acute kidney injury (AKI) is a frequent and serious
      complication after cardiac surgery. Clinical factors alone have failed to
      accurately predict the incidence of AKI after cardiac surgery. Ethnicity has been
      shown to be a predictor of AKI in the Western population. We tested the
      hypothesis that ethnicity is an independent predictor of AKI in patients
      undergoing cardiac surgery in a South East Asian population. METHODS: A total of
      1756 consecutive patients undergoing cardiac surgery were prospectively
      recruited. Among them, data of 1639 patients met the criteria for analysis. There
      were 1182 Chinese, 195 Indian, and 262 Malay patients. The main outcome was
      postoperative AKI, defined as a 25% or greater increase in preoperative to a
      maximum postoperative serum creatinine level within 3 days after surgery.
      RESULTS: Five hundred and seventy-nine patients (35.3%) developed AKI after
      cardiac surgery. Ethnicity was shown to be an independent predictor of AKI after
      cardiac surgery with Indians and Malays having a higher risk of developing AKI
      when compared with Chinese patients (odds ratio: Indian vs Chinese 1.44, Malay vs
      Chinese 1.51). CONCLUSIONS: Indians and Malays have a higher risk of developing
      AKI after cardiac surgery than Chinese in a South East Asian population.
      Ethnicity was shown to be an independent predictor of AKI after cardiac surgery.

PMID- 23171724
TI  - Patients with end-stage renal disease admitted to the intensive care unit:
      systematic review.
AB  - The number of patients with end-stage renal disease (ESRD) is increasing
      worldwide, with a growing demand on healthcare services. A systematic review of
      the literature was performed to determine the requirement for intensive care unit
      (ICU) services, reasons for admission, predictors of mortality, and short- and
      long-term outcomes of ESRD patients admitted to ICU. Sixteen studies were
      identified, comprising 6591 ICU admissions. Cardiovascular disease and sepsis
      accounted for the majority of admissions. Acute illness severity scores tend to
      overestimate mortality among ESRD patients. Critical illness associated with
      acute kidney injury (AKI) requiring renal replacement therapy (RRT) is associated
      with significantly higher hospital mortality compared with ESRD patients admitted
      to the ICU [odds ratio (OR) 3.9; 3.5-4.4; P<0.0001]. However, hospital mortality
      of ESRD patients is less favourable compared with matched patients with mild AKI
      (OR 1.5; 1.4-1.6; P<0.0001). Although the mortality rate remains high shortly
      after hospital discharge, the duration of increased mortality risk is unclear.
      Patients with ESRD frequently benefit from ICU admission, despite chronic co
      morbidity. Further studies are required to modify and validate existing illness
      severity scores for ESRD patients admitted to the ICU, and to establish the
      duration of increased mortality risk after discharge from ICU.

PMID- 23171725
TI  - Stroke volume optimization in elective bowel surgery: a comparison between pulse
      power wave analysis (LiDCOrapid) and oesophageal Doppler (CardioQ).
AB  - BACKGROUND: Goal-directed fluid therapy improves outcome in major surgery. We
      evaluated a new device (LiDCOrapid) against our standard oesophageal Doppler
      method (ODM) for stroke volume (SV) optimization during colorectal surgery.
      METHODS: This was an observational study in 20 patients undergoing major
      colorectal surgery within a fast-track protocol. We compared SV values measured
      simultaneously by LiDCOrapid and ODM before and after 86 fluid challenges. We
      also evaluated the LiDCOrapid dynamic indices SV variation (SVV) and pulse
      pressure variation (PPV) as predictors for volume responsiveness, defined as an
      increase in SV >= 10% after 200 ml of colloid. RESULTS: SV increased >= 10% after
      27 out of 86 fluid challenges. For 172 paired SV values, the overall correlation
      was r=0.39, and bias (limits of agreement) -28 (-91-35) ml, percentage error 70%.
      The ability of LiDCOrapid to track changes in SV was weak with a concordance rate
      of 80%, and a sensitivity and specificity of 48% and 81%, respectively, to detect
      a positive fluid challenge. The area under the curve values (with 95% confidence
      intervals) for SVV and PPV were 0.72 (0.60-0.83) and 0.66 (0.52-0.79),
      respectively, indicating low predictive capacity in these setting. CONCLUSIONS:
      LiDCOrapid and ODM devices are not interchangeable. We cannot recommend that the
      LiDCOrapid replace the standard Doppler method until further device-specific
      outcome studies on volume optimization are available. The dynamic indices SVV and
      PPV add little value to a fluid optimization protocol, and should not replace SV
      measurements with a validated technique.

PMID- 23171726
TI  - Intraoperative tissue oxygenation and postoperative outcomes after major non
      cardiac surgery: an observational study.
AB  - BACKGROUND: The relationship between tissue oxygen saturation (StO(2)) and
      serious postoperative complications remains unclear. We tested the hypothesis
      that perioperative in patients undergoing major non-cardiac surgery is inversely
      related to serious surgical outcomes. METHODS: We enrolled 124 patients, ASA
      physical status <=IV, having elective major non-cardiac surgeries with general
      anaesthesia. An InSpectra Model 650 StO(2) monitor (Hutchinson Technology,
      Hutchinson, MN, USA) was used to measure at the thenar eminence throughout
      surgery and for two postoperative hours. Our primary outcome was a composite of
      30 day mortality and serious in-hospital complications. The secondary outcome was
      an a priori subset of the primary composite outcome representing infectious and
      wound-healing complications. Multivariable logistic regression was used to
      evaluate the associations between our primary and secondary outcomes and time
      weighted average (TWA) and minimum . RESULTS: Patients were 61 (12), mean (SD) yr
      old. The minimum was inversely associated with our primary composite outcome
      (P=0.02). The estimated odds ratio (97.5% CI) of having any major postoperative
      morbidity was 0.82 (0.67, 1.00) for a 5% increase in the minimum . In contrast,
      TWA was not significantly associated with major postoperative morbidity (P=0.35).
      Furthermore, neither TWA (P=0.65) nor minimum (P=0.70) was significantly
      associated with wound complications. CONCLUSIONS: Minimum perioperative
      peripheral tissue oxygenation predicted a composite of major complications and
      mortality from major non-cardiac surgery. This is an observational association
      and whether clinical interventions to augment tissue oxygenation will improve
      outcomes remains to be determined.

PMID- 23171727
TI  - The genetic contribution to disease risk and variability in response to diet:
      where is the hidden heritability?
AB  - Ten years ago, it was assumed that disease risk prediction and personalised
      nutrition based on genetic information would now be in widespread use. However,
      this has not (yet) transpired. The interaction of genetic make-up, diet and
      health is far more complex and subtle than originally thought. With a few notable
      exceptions, the impact of identified common genetic variants on phenotype is
      relatively small and variable in their penetrance. Furthermore, the known
      variants account for only a fraction of what we believe to be the total genetic
      contribution to disease risk and heterogeneity in response to environmental
      change. Here, the question 'how far have we progressed and are we likely to get
      there' (Rimbach and Minihane, 2009) is revisited with regard to the translation
      of genetic knowledge into public health benefit. It is concluded that progress to
      date has been modest. It is hoped that recent technological developments allowing
      the detection of rarer variants and future use of more hypothesis-driven targeted
      data analysis will reveal most of the currently 'hidden' significant genetic
      variability.

PMID- 23171728
TI  - Nonprimate hepaciviruses in domestic horses, United kingdom.
AB  - Although the origin of hepatitis C virus infections in humans remains
      undetermined, a close homolog of this virus, termed canine hepacivirus (CHV) and
      found in respiratory secretions of dogs, provides evidence for a wider
      distribution of hepaciviruses in mammals. We determined frequencies of active
      infection among dogs and other mammals in the United Kingdom. Samples from dogs
      (46 respiratory, 99 plasma, 45 autopsy samples) were CHV negative by PCR.
      Screening of 362 samples from cats, horses, donkeys, rodents, and pigs identified
      3 (2%) positive samples from 142 horses. These samples were genetically divergent
      from CHV and nonprimate hepaciviruses that horses were infected with during 2012
      in New York state, USA. Investigation of infected horses demonstrated nonprimate
      hepacivirus persistence, high viral loads in plasma (10(5)-10(7) RNA copies/mL),
      and liver function test results usually within reference ranges, although several
      values ranged from high normal to mildly elevated. Disease associations and host
      range of nonprimate hepaciviruses warrant further investigation.

PMID- 23171729
TI  - Calpain and atherosclerosis.
AB  - This review highlights the pro-atherogenic roles of Ca(2+)-sensitive
      intracellular protease calpains. Among more than ten species of calpain isozymes,
      u- and m-calpains have been characterized most extensively. These two isozymes
      are ubiquitously expressed in mammalian tissues, including blood vessels, and
      tightly regulate functional molecules in the vascular component cells through
      limited proteolytic cleavage. Indeed, previous cell-based experiments showed that
      calpains play significant roles in nitric oxide production in vascular
      endothelial cells (ECs), maintenance of EC barrier function and angiogenesis for
      maintaining vascular homeostasis. Recently, we demonstrated that modified-low
      density lipoprotein (LDL)-induced m-calpain causes hyperpermeability in ECs,
      leading to the infiltration of monocytes/macrophages and plasma lipids into the
      intimal spaces (Miyazaki T. et al., Circulation. 2011; 124: 2522-2532). Calpains
      also mediate oxidized LDL-induced apoptotic death in ECs. In
      monocytes/macrophages, calpains induce proteolytic degradation of ATP-binding
      cassette transporter A1 (ABCA1) and G1 (ABCG1), which results in impaired
      cholesterol efflux and subsequent macrophage foam cell formation. In vascular
      smooth muscle cells, calpains may be involved in the conversion from contractile
      phenotype to proliferative phenotype. In hepatocytes, calpains disrupt the
      biogenesis of high-density lipoprotein via proteolytic degradation of ABCA1.
      Thus, calpains may serve as novel candidate molecular targets for control of
      atherosclerosis.

PMID- 23171731
TI  - Effects of glial cell line-derived neurotrophic factor, fibroblast growth factor
      2 and epidermal growth factor on proliferation and the expression of some genes
      in buffalo (Bubalus bubalis) spermatogonial cells.
AB  - The present study evaluated the effects of glial cell line-derived neurotrophic
      factor (GDNF), fibroblast growth factor (FGF) 2 and epidermal growth factor (EGF)
      on proliferation and the expression of some genes in spermatogonial cells.
      Spermatogonial cells were isolated from prepubertal buffalo testes and enriched
      by double enzyme treatment, filtration through 80- and 60-MUm nylon mesh filters,
      differential plating on lectin-coated dishes and Percoll density gradient
      centrifugation. Cells were then cultured on a buffalo Sertoli cell feeder layer
      and formed colonies within 15-18 days. The colonies were found to predominantly
      contain undifferentiated Type A spermatogonia because they bound Dolichos
      biflorus agglutinin and did not express c-kit. The colonies expressed alkaline
      phosphatase, NANOG, octamer-binding transcription factor (OCT)-4 and tumour
      rejection antigen (TRA)-1-60. Cells were subcultured for 15 days, with or without
      growth factor supplementation. After 15 days, colony area and the relative mRNA
      abundance of PLZF were higher (P<0.05) following supplementation with 40 ng mL-1
      GDNF + 10 ng mL-1 EGF + 10 ng mL-1 FGF2 than with the same concentrations of GDNF
      alone or GDNF plus either EGF or FGF2. Expression of TAF4B was higher (P<0.05) in
      the presence of FGF2, whereas the expression of THY1 was not affected by growth
      factor supplementation. In the Sertoli cell feeder layer, EGF and FGF2 decreased
      (P<0.05), whereas GDNF increased (P<0.05), the relative mRNA abundance of ETV5
      compared with control. In conclusion, an in vitro culture system that
      incorporates various growth factors was developed for the short-term culture of
      buffalo spermatogonia.

PMID- 23171732
TI  - Toxocara cati larva migrans in domestic pigs--detected at slaughterhouse control
      in Norway.
AB  - Routine Trichinella meat inspection at the slaughterhouse detected one larva in a
      pooled batch of 100 pig samples. The larva was sent to the Norwegian Veterinary
      Institute (NVI) for species identification.Morphological examination revealed
      that the larva was not Trichinella spp. Molecular analysis was performed. PCR and
      sequencing of 5S/ITS identified the larva as Toxocara cati. A second round of
      digests was carried out at the meat inspection laboratory, in smaller batches to
      try to identify the infected animal. No further larvae were detected and it was
      not possible to identify which of the 100 animals the larva had come from. This
      is the first time that Toxocara cati has been reported in slaughterhouse pigs in
      Norway.Although the infected individual could not be identified, the meat
      originated from one of six potential farms. A small survey regarding rodent
      control and cats was sent to each of these farms. Cats had restricted access to
      food storage areas (two farms reported that cats had access) whilst none of the
      farms allowed cats into the production housing. Cats were, however, present on
      all the farms (mostly stray cats of unknown health status). Half of the farms
      also reported seeing rodents in the pig housing during the previous six months
      and half reported finding rodents in the feed and straw storage areas. We were
      unable to narrow down the source of infection - however contamination of food or
      bedding material, with cat faeces or infected rodents, in addition to the
      presence of infected rodents in pig housing remain potential routes of infection.

PMID- 23171733
TI  - CXCR3 blockade: a novel anti-sepsis approach?
AB  - Blockade of the CXC chemokine receptor 3 (CXCR3) attenuates inflammation and
      improves survival in a murine model of near lethal polymicrobial sepsis. However,
      given the multitude of cellular responses and inflammatory mediators that
      orchestrate sepsis syndrome, more detailed investigations will be required before
      a complete understanding of the mechanism(s) of CXCR3 blockade and its
      therapeutic potential are revealed. 

PMID- 23171734
TI  - The clinical significance of PCDH10 promoter methylation in patients with bladder
      transitional cell carcinoma.
AB  - OBJECTIVE: To investigate the clinical significance of PCDH10 (protocadherin 10)
      promoter methylation in patients with bladder transitional cell carcinoma (TCC).
      MATERIALS AND METHODS: 107 samples of bladder TCC and 38 normal bladder
      epithelial tissues were investigated using methylation-specific PCR, and the
      relationships between PCDH10 methylation and clinicopathologic features as well
      as patients' outcome were analyzed. RESULTS: PCDH10 methylation was detected in
      63 (58.9%) bladder TCC samples, but no methylation of PCDH10 was found in
      controls. Moreover, PCDH10 methylation was significantly associated with larger
      tumor size (p = 0.0074), non-papillary shape (p = 0.0268), tumor relapse (p =
      0.0029), high grade (p = 0.0397), advanced stage (p = 0.0004) and poor prognosis
      (p = 0.0009). In addition, multivariate analysis indicated that PCDH10
      methylation is independently associated with poor outcome and may be used as a
      useful independent prognostic factor (p = 0.0255). CONCLUSIONS: PCDH10
      methylation is closely associated with malignancy of bladder TCC and may be used
      as an independent predictor for patients with bladder TCC.

PMID- 23171730
TI  - Long-term exposure to particulate matter in relation to mortality and incidence
      of cardiovascular disease: the JPHC Study.
AB  - AIM: Associations between long-term exposure to particulate matter (PM) and
      increased cardiovascular mortality have been reported, but few studies have
      investigated the associated incidence of cardiovascular disease, and none
      involved men. METHODS: We used data on 78,057 participants (37,121 men, 40,936
      women) to examine the associations of long-term exposure to PM with mortality and
      the incidence of cardiovascular diseases. Average PM levels in the relevant area
      during the study period were used as an index of individual exposure to each
      subject. Cox models adjusted for age, sex, smoking, environmental smoking, body
      mass index, and alcohol consumption were used, with further adjustments for
      nitrogen dioxide and sulfur dioxide exposure, systolic blood pressure, total
      cholesterol, and diabetes mellitus. RESULTS: Increased PM levels were associated
      with an increased risk of incident coronary heart disease (CHD) and myocardial
      infarction (MI), particularly among smokers (adjusted hazard ratio (HR) per 10
      ug/m(3) increase in PM for CHD: 1.39, 95% confidence interval (CI) 1.01-1.93; for
      MI: 1.52, 1.08-2.13) and among women (for CHD: 1.63, 0.91-2.92; for MI: 1.99,
      1.07-3.70); however, the observed positive association of PM exposure with the
      incidence of CHD and MI was not robust, and the association disappeared when one
      of the areas (Akita) was excluded. The association with CHD mortality was not
      statistically significant (adjusted HR per 10 ug/m(3) increase in PM: 1.11, 0.92
      1.33). There was an inverse association of long-term PM exposure with stroke
      mortality and incidence. There was no clear association between PM levels and
      lung cancer mortality and incidence. CONCLUSIONS: Long-term exposure to PM might
      increase the risk of incident CHD in middle-aged Japanese men and women. Our
      findings also suggest that women and smokers are especially vulnerable to PM
      exposure.

PMID- 23171735
TI  - Correction: HP1gamma function is required for male germ cell survival and
      spermatogenesis.

PMID- 23171736
TI  - Reemergence of Chikungunya virus in Cambodia.
AB  - Chikungunya virus (CHIKV), probably Asian genotype, was first detected in
      Cambodia in 1961. Despite no evidence of acute or recent CHIKV infections since
      2000, real-time reverse transcription PCR of serum collected in 2011 detected
      CHIKV, East Central South African genotype. Spatiotemporal patterns and
      phylogenetic clustering indicate that the virus probably originated in Thailand.

PMID- 23171737
TI  - Effects of carpal tunnel syndrome on adaptation of multi-digit forces to object
      mass distribution for whole-hand manipulation.
AB  - BACKGROUND: Carpal tunnel syndrome (CTS) is a compression neuropathy of the
      median nerve that results in sensorimotor deficits in the hand. Until recently,
      the effects of CTS on hand function have been studied using mostly two-digit grip
      tasks. The purpose of this study was to investigate the coordination of multi
      digit forces as a function of object center of mass (CM) during whole-hand
      grasping. METHODS: Fourteen CTS patients and age- and gender-matched controls
      were instructed to grasp, lift, hold, and release a grip device with five digits
      for seven consecutive lifts while maintaining its vertical orientation. The
      object CM was changed by adding a mass at different locations at the base of the
      object. We measured forces and torques exerted by each digit and object
      kinematics and analyzed modulation of these variables to object CM at object lift
      onset and during object hold. Our task requires a modulation of digit forces at
      and after object lift onset to generate a compensatory moment to counteract the
      external moment caused by the added mass and to minimize object tilt. RESULTS: We
      found that CTS patients learned to generate a compensatory moment and minimized
      object roll to the same extent as controls. However, controls fully exploited the
      available degrees of freedom (DoF) in coordinating their multi-digit forces to
      generate a compensatory moment, i.e., digit normal forces, tangential forces, and
      the net center of pressure on the finger side of the device at object lift onset
      and during object hold. In contrast, patients modulated only one of these DoFs
      (the net center of pressure) to object CM by modulating individual normal forces
      at object lift onset. During object hold, however, CTS patients were able to
      modulate digit tangential force distribution to object CM. CONCLUSIONS: Our
      findings suggest that, although CTS did not affect patients' ability to perform
      our manipulation task, it interfered with the modulation of specific grasp
      control variables. This phenomenon might be indicative of a lower degree of
      flexibility of the sensorimotor system in CTS to adapt to grasp task conditions.

PMID- 23171738
TI  - Antipsychotic compounds differentially modulate high-frequency oscillations in
      the rat nucleus accumbens: a comparison of first- and second-generation drugs.
AB  - Improved understanding of the actions of antipsychotic compounds is critical for
      a better treatment of schizophrenia. Abnormal oscillatory activity has been found
      in schizophrenia and in rat models of the disease. N-Methyl-D-aspartic acid
      receptor (NMDAR) antagonists, used to model certain features of schizophrenia,
      increase the frequency and power of high-frequency oscillations (HFO, 130-180 Hz)
      in the rat nucleus accumbens, a brain region implicated in schizophrenia
      pathology. Antipsychotics can be classified as first- and second-generation
      drugs, the latter often reported to have wider benefit in humans and experimental
      models. This prompted the authors to examine the pre- and post-treatment effects
      of clozapine, risperidone (second-generation drugs) and sulpiride and haloperidol
      (first-generation drugs) on ketamine and MK801-enhanced accumbal HFO. Both NMDAR
      antagonists increased HFO frequency. In contrast, clozapine and risperidone
      markedly and dose-dependently reduced the frequency of spontaneous and NMDAR
      antagonist-enhanced HFO, whilst a moderate effect was found for sulpiride and a
      much weaker effect for haloperidol. Unexpectedly, we found reductions in HFO
      frequency were associated with an increase in its power. These findings indicate
      that modulation of accumbal HFO frequency may be a fundamental effect produced by
      antipsychotic compounds. Of the drugs investigated, first- and second-generation
      compounds could be dissociated by their potency on this measure. This effect may
      partially explain the differences in the clinical profile of these drugs.

PMID- 23171739
TI  - embB306 mutations as molecular indicators to predict ethambutol susceptibility in
      Mycobacterium tuberculosis.
AB  - BACKGROUND: Discordant results in conventional susceptibility testing of
      ethambutol against Mycobacterium tuberculosis may lead to underreporting of drug
      resistance. METHODS: A 240-bp region of the embB gene in 111 clinical isolates of
      M. tuberculosis was sequenced and examined for mutations linked to ethambutol
      resistance. The phenotypic susceptibility levels of the isolates were quantified
      by the BACTECTM MGIT 960TM TB System and correlated with the genotypic test
      results. These data were analyzed to find information that could be used to
      clarify discordant ethambutol susceptibility test results. RESULTS: Mutations
      M306I (n = 56), M306V (n = 18) and M306L (n = 3) in M. tuberculosis showed
      decreased susceptibility to ethambutol. The minimum inhibitory concentrations
      (MICs) in 73% (56/77) of embB306 mutants were at or just above the critical
      concentration (MICs, 5.0 to <=12.5 ug/ml) of ethambutol reflecting borderline (or
      intermediate) resistance. Eight ethambutol-resistant isolates lacked embB
      mutations, probably due to mutational alterations elsewhere in the genome.
      CONCLUSION: Our findings suggest that clinical isolates containing embB306
      mutations with MICs overlapping the critical concentration are associated with
      discordant ethambutol susceptibility test results. The clinical significance of
      borderline resistance in combination treatment of tuberculosis remains to be
      determined before alternative ethambutol breakpoints are considered.

PMID- 23171740
TI  - Avian influenza vaccination of poultry and passive case reporting, Egypt.
AB  - We investigated the influence of a mass poultry vaccination campaign on passive
      surveillance of highly pathogenic avian influenza subtype (H5N1) outbreaks among
      poultry in Egypt. Passive reporting dropped during the campaign, although
      probability of infection remained unchanged. Future poultry vaccination campaigns
      should consider this negative impact on reporting for adapting surveillance
      strategies.

PMID- 23171742
TI  - Surgical improvement of speech disorder caused by amyotrophic lateral sclerosis.
AB  - Amyotrophic lateral sclerosis (ALS) is a progressive debilitating neurological
      disease.  ALS disturbs the quality of life by affecting speech, swallowing and
      free mobility of the arms without affecting intellectual function.  It is
      therefore of significance to improve intelligibility and quality of speech
      sounds, especially for ALS patients with slowly progressive courses.  Currently,
      however, there is no effective or established approach to improve speech disorder
      caused by ALS.  We investigated a surgical procedure to improve speech disorder
      for some patients with neuromuscular diseases with velopharyngeal closure
      incompetence.  In this study, we performed the surgical procedure for two
      patients suffering from severe speech disorder caused by slowly progressing ALS. 
      The patients suffered from speech disorder with hypernasality and imprecise and
      weak articulation during a 6-year course (patient 1) and a 3-year course (patient
      2) of slowly progressing ALS.  We narrowed bilateral lateral palatopharyngeal
      wall at velopharyngeal port, and performed this surgery under general anesthesia
      without muscle relaxant for the two patients.  Postoperatively, intelligibility
      and quality of their speech sounds were greatly improved within one month without
      any speech therapy.  The patients were also able to generate longer speech
      phrases after the surgery.  Importantly, there was no serious complication during
      or after the surgery.  In summary, we performed bilateral narrowing of lateral
      palatopharyngeal wall as a speech surgery for two patients suffering from severe
      speech disorder associated with ALS.  With this technique, improved
      intelligibility and quality of speech can be maintained for longer duration for
      the patients with slowly progressing ALS.

PMID- 23171741
TI  - Virulent avian infectious bronchitis virus, People's Republic of China.
AB  - A virulent avian infectious bronchitis virus (IBV) was isolated from 30-day-old
      broiler chickens that exhibited respiratory symptoms, nephropathologic lesions,
      and a high proportion of deaths in the People's Republic of China during 2005.
      The strain, designated YN, was genetically and pathologically characterized.
      Phylogenetic analysis showed that YN and most of the previously characterized IBV
      isolates found in China were phylogenetically classified into 2 main genetic
      clusters. The YN isolate caused severe lesions and resulted in deaths of 65% in
      experimental infections of 30-day-old specific-pathogen-free chickens. Tracheal
      and severe kidney lesions developed in all infected birds, confirming the ability
      of YN strain to induce both respiratory and renal disease. IBV antigens were
      detected by immunohistochemical analysis in the trachea, lung, kidney, and bursa,
      consistent with histopathologic observations, virus isolation, and reverse
      transcription PCR detection. We showed that YN IBV exhibits severe pathogenicity
      in chickens, and that similar viruses are prevalent in China.

PMID- 23171743
TI  - Isolation and molecular characterization of type I and type II feline coronavirus
      in Malaysia.
AB  - BACKGROUND: Feline infectious peritonitis virus (FIPV) and feline enteric
      coronavirus (FECV) are two important coronaviruses of domestic cat worldwide.
      Although FCoV is prevalent among cats; the fastidious nature of type I FCoV to
      grow on cell culture has limited further studies on tissue tropism and
      pathogenesis of FCoV. While several studies reported serological evidence for
      FCoV in Malaysia, neither the circulating FCoV isolated nor its biotypes
      determined. This study for the first time, describes the isolation and biotypes
      determination of type I and type II FCoV from naturally infected cats in
      Malaysia. FINDINGS: Of the total number of cats sampled, 95% (40/42) were RT-PCR
      positive for FCoV. Inoculation of clinical samples into Crandell feline kidney
      cells (CrFK), and Feline catus whole fetus-4 cells (Fcwf-4), show cytopathic
      effect (CPE) characterized by syncytial cells formation and later cell
      detachment. Differentiation of FCoV biotypes using RT-PCR assay revealed that,
      97.5% and 2.5% of local isolates were type I and type II FCoV, respectively.
      These isolates had high sequence homology and phylogenetic similarity with
      several FCoV isolates from Europe, South East Asia and USA. CONCLUSIONS: This
      study reported the successful isolation of local type I and type II FCoV evident
      with formation of cytopathic effects in two types of cell cultures namely the
      CrFK and Fcwf-4 , where the later cells being more permissive. However, the RT
      PCR assay is more sensitive in detecting the antigen in suspected samples as
      compared to virus isolation in cell culture. The present study indicated that
      type I FCoV is more prevalent among cats in Malaysia.

PMID- 23171744
TI  - Affect regulation and psychopathology in women with borderline personality
      disorder.
AB  - INTRODUCTION: Dysfunction in affect regulation is a prominent feature that
      grossly impairs behavioural and interpersonal domains of experience and underlies
      a great deal of the psychopathology in borderline personality disorder (BPD).
      However, no study has yet been published that evaluates the psychometric
      properties of the translated Danish version of self-report measures sensitive to
      the different aspects and dimensions of dysfunction in affect regulation
      prevalent in BPD. MATERIAL AND METHODS: This study comprised a group of women
      diagnosed with BPD (n = 29) and a comparison group of healthy subjects (n = 29)
      who reported psychopathology and levels of affective instability, aggression,
      impulsivity and alexithymia by self-report measures. RESULTS: Our results
      demonstrated that women with BPD have significant psychopathology and report
      significantly higher levels of dysfunction in separate components of affect
      regulation by self-report measures than the comparison group of healthy subjects.
      Our results also provided partial support for the psychometric appropriateness
      and clinical relevance of the translated Danish version of affect regulation
      measures. CONCLUSION: The normative reference range indicated by our results
      makes the measures useful as a practical assessment tool. FUNDING: not relevant.
      TRIAL REGISTRATION: not relevant.

PMID- 23171745
TI  - Comparison of Child Behavior Checklist subscales in screening for obsessive
      compulsive disorder.
AB  - INTRODUCTION: Obsessive-compulsive disorder (OCD) is a prevalent psychiatric
      disorder in children and adolescents associated with significant functional
      impairment. Early and correct diagnosis is essential for an optimal treatment
      outcome. The purpose of this study was to determine which of four subscales
      derived from the Child Behavior Checklist best discriminates OCD patients from
      clinical and population-based controls. MATERIAL AND METHODS: The material
      consisted of 84 children diagnosed with OCD, 84 clinical controls and 84 general
      population controls with no psychiatric record. RESULTS: Receiver operating
      characteristics analyses identified the best cut-off scores of the scales. There
      was no significant difference in the discriminating ability of the scales.
      Sensitivity, specificity, positive and negative predictive value were calculated
      for single items and scales at cut-point levels. CONCLUSION: None of the scales
      examined were superior to the others. The extended scales were no better than a
      scale comprising the two core items, obsessions and compulsions. FUNDING: not
      relevant. TRIAL REGISTRATION: not relevant.

PMID- 23171746
TI  - Steady progress seen in endoscopic surgery on major salivary glands.
AB  - INTRODUCTION: The objective of this study was to investigate the development in
      sialendoscopy (SE) in East Denmark. Data were compared with previously published
      data to assess the learning curve. MATERIAL AND METHODS: In this retrospective
      consecutive study, all patients who had SE performed at Hillerod Hospital from
      November 2009 to April 2011 were included. Data were extracted from medical
      records and interviews. Two surgeons performed all SEs. Z-test and Fisher's exact
      test were used for statistical analysis. RESULTS: A total of 118 patients met the
      inclusion criteria. In all, 156 diagnostic and 139 therapeutic SEs were
      performed. The median age was 44 years (3-85 years) and the female-to-male-ratio
      was 1.81. A total of 96% of patients had pre-operative ultrasound performed (the
      positive predictive value for detection of stone was 0.82, 95% confidence
      interval 0.70-0.90. Indication for SE was recurrent or chronic swelling, pain,
      identified stone or recurrent infections. The only exclusion criterion was
      neoplasms. The success rate of diagnostic SE was 98%, and the therapeutic SE
      success rate was 67%. Total or partial relief from symptoms was obtained in 77%
      of patients which was a significant improvement (Z-test: p < 0.001). No serious
      persistent complications occurred. CONCLUSION: SE is a safe and effective
      treatment for benign obstructive disease of the major salivary glands. The
      surgeon's results improve significantly over time. Updated equipment and an
      experienced surgeon yielded patient symptom relief in 77% of cases. FUNDING: not
      relevant. TRIAL REGISTRATION: This study was approved by the Danish Committee on
      Biomedical Research Ethics and the Danish Data Protection Agency.

PMID- 23171747
TI  - Customization of a tool to assess Danish surgeons' non-technical skills in the
      operating room.
AB  - INTRODUCTION: Errors in surgery often stem from failure related to non-technical
      skills such as communication and teamwork. Tools for training and assessment of
      non-technical skills are needed to ensure safe surgery. The aim of this study was
      to customize the Non-Technical Skills for Surgeons (NOTSS) rating system for
      Danish general surgeons. MATERIAL AND METHODS: Eight group interviews were
      conducted at two hospitals with consultant general surgeons, trainee surgeons,
      scrub nurses and anaesthesia staff (n = 72). Interviews were transcribed and
      analysed by two coders identifying surgeons' non-technical skills. Skills were
      sorted according to NOTSS and behavioural examples were written. The prototype of
      NOTSSdk was discussed with a panel of surgeons (n = 12) to ensure face validity.
      RESULTS: The skills identified in a Danish context fitted NOTSS's four
      categories: situation awareness, decision making, leadership, communication and
      teamwork and the 12 underlying elements. Only one element was added to the
      NOTSSdk; "monitoring own performance." A total of 3-8 good and 3-6 poor
      behavioural examples were written for each element. Respecting team members,
      creating a good working atmosphere and discussing options in the surgical team
      were distinct themes. DISCUSSION: The tool, which was customized for Danish
      surgeons, comprises four categories, 13 elements and numerous behavioural
      examples. The distinct themes regarding respect, discussing options and creating
      a good working atmosphere are more prominent than in the Scottish NOTSS, which
      may be explained by cultural differences or the fact that the present study
      included the perspectives of the entire surgical team. CONCLUSION: NOTSSdk holds
      potential as a tool for the guiding of assessment and feedback on surgeons' non
      technical performance. FUNDING: not relevant. TRIAL REGISTRATION: The study was
      registered with clinicaltrials.gov (NCT01334411).

PMID- 23171748
TI  - Risk of perforation using rigid oesophagoscopy in the distal part of oesophagus.
AB  - INTRODUCTION: Endoscopic examination and treatment of disorders in the oesophagus
      have been a part of the otolaryngological specialty since the introduction of the
      rigid endoscope. Today, both flexible and rigid oesophagoscopy (RO) is used to
      that end. The aim of this study was to evaluate the safety of the RO. MATERIAL
      AND METHODS: We conducted a retrospective cohort study of all ROs performed at a
      head & neck department in a Danish hospital in the 2003-2011-period. Perforation
      of the oesophageal wall was the primary endpoint. Secondary endpoints included:
      dental injury, mortality and, in case of a foreign body: location and successful
      removal. RESULTS: A total of 483 ROs were performed. Four patients (0.8%)
      suffered perforation; three during removal of a foreign body in the lower part of
      the oesophagus and one as part of investigation for cancer. 46.2% of the
      procedures were performed to remove a foreign body and 32.7% as investigation for
      cancer. The majority of the foreign bodies were located in the superior part of
      the oesophagus and the objects were successfully removed in all but one case.
      CONCLUSION: Our results are well within the range of previously published
      material. We recommend that the risk of serious complications is taken into
      consideration when choosing this modality. Furthermore, we believe that this risk
      increases in the distal part of the oesophagus and recommend that the use of the
      RO in this area is reserved as a last resort option. FUNDING: not relevant. TRIAL
      REGISTRATION: not relevant.

PMID- 23171749
TI  - High dosage of dextran 70 is associated with severe bleeding in patients admitted
      to the intensive care unit for septic shock.
AB  - INTRODUCTION: Synthetic colloids are frequently used in fluid resuscitation of
      septic patients. Despite this, little is known about the potential side effects
      including the risk of renal failure and bleeding. As practice has changed, we
      performed a before-and-after study of fluid resuscitation and outcome in patients
      with septic shock. MATERIAL AND METHODS: We retrospectively assessed all adult
      patients with septic shock admitted to a general intensive care unit (ICU) at a
      tertiary hospital in the years 2006 and 2008. Data on patient characteristics,
      resuscitation fluids in the ICU and outcome were collected from electronic
      databases and patient files. RESULTS: A total of 332 patients with septic shock
      were included: 171 in 2006 and 161 in 2008. The use of mainly dextran 70 in 2006
      (median 3.5 (interquartile range 1.9-7.1) versus 1.5 (0.5-3.0) l, p < 0.0001; 44
      (24-86) versus 18 (8-42) ml/kg, p < 0.0001) had changed to mainly crystalloids
      (Ringer's lactate 0 (0.0-0.3) versus 1.1 (0.0-3.0) l, p < 0.0001) and albumin
      (5%, 0.0 (0.0-1.0) versus 0.8 (0.0-1.5) l, p < 0.0001; 20%, 0.0 (0.0-0.3) versus
      0.1 (0.0-0.4) l, p < 0.0001) in 2008. There were no differences in rates of renal
      replacement therapy or 90-day mortality, but more patients experienced severe
      bleeding in 2006 than in 2008 (30 versus 19%, p = 0.03). Also more red blood
      cells, plasma and platelets were given in 2006 than in 2008 (p < 0.01 for all).
      CONCLUSION: In patients with septic shock, fluid treatment had changed from
      mainly dextran 70 in 2006 to crystalloids and albumin in 2008. The administration
      of high-dosage dextran 70 was associated with more patients experiencing severe
      bleeding. FUNDING: not relevant. TRIAL REGISTRATION: not relevant.

PMID- 23171750
TI  - Medication problems are frequent and often serious in a Danish emergency
      department and may be discovered by clinical pharmacists.
AB  - INTRODUCTION: Transferring a patient from one health-care sector to another
      implies a risk of medication errors. It is of interest to evaluate whether a
      specialist in clinical pharmacy is beneficial for the patients in the emergency
      departments (ED). The aim of the present study was to report the incidence,
      categories and seriousness of medication problems discovered by clinical
      pharmacists in an ED and to evaluate if it is possible for pharmacists to
      identify those groups of patients who are most at risk of medication problems.
      MATERIAL AND METHODS: A pharmacist reviewed the patient files in the ED. If the
      pharmacists provided any kind of recommendations, a note was made describing the
      problem and a suggestion for a solution. After the study period, two medical
      specialists reviewed the files and rated the suggestions according to four levels
      of importance. RESULTS: A total of 1,696 patient files were reviewed after
      excluding patients who had received no medication. A total of 420 pharmacist
      notes were written, corresponding to 25% of all the included admissions. 47% of
      the pharmaceutical suggestions were considered serious. Increasing age and one
      drug as opposed to 2-9 drugs were associated with serious recommendations. In the
      multivariate analysis, only age above 70 years remained of significance for the
      identification of patients with a risk of a serious medication problem.
      CONCLUSION: A considerable amount of serious pharmaceutical problems were found
      in the ED. These problems had not been observed by the physicians and they were
      especially prevalent among the elderly and patients who were only prescribed a
      single drug. FUNDING: The Amgros research foundation financed salaries for the
      independent specialists who reviewed the patient files. TRIAL REGISTRATION: not
      relevant.

PMID- 23171751
TI  - Functional somatic symptoms in 5-7 year old children: assessment, prevalence and
      co-occurrence.
AB  - Medically unexplained or functional somatic symptoms (FSS) in children constitute
      a major clinical problem. However, research data on FSS in young children are
      few, and epidemiological studies are hampered by lack of good standardised
      measures.   The present thesis consists of two studies:   In study one, we
      developed two measures to assess FSS in young children. The first measure is a
      parent interview, the Soma Assessment Interview (SAI), to assess the 1-year
      prevalence and associated impairment caused by FSS. The interview can be
      performed by lay interviewers and subsequently rated clinically by physicians. A
      preliminary validation showed a good agreement on FSS recognition between two
      clinical raters (kappa = 0.86), a good concurrent validity with independent
      measures of physical complaints and a good discrimination on the prevalence of
      FSS between a community sample and clinical samples.   The second measure is a
      systematic medical record review of FSS in paediatric patients: the Medical
      Record Review for Functional Somatic Symptoms in Children (MRFC). Our findings
      suggest that the MRFC allows identification of subgroups of paediatric patients
      with multisymptomatic FSS and long-term and/or impairing FSS and it may prove
      useful for case finding in clinical and epidemiological research.   In study two,
      we investigated the parent-reported FSS and their impairment in a population
      based sample of Danish 5-7-year-old children. We used the SAI as the main
      measure. Data from 1,327 children from The Copenhagen Child Cohort 2000 were
      analysed. Impairing symptoms were defined as FSS causing substantial discomfort,
      impairment of everyday life, absence from daycare or school and/or health care
      seeking. We found that FSS are common in this age group with a 1-year prevalence
      of 23.2%. Different pain complaints, i.e. limb pain, abdominal pain and headache,
      were the most prevalent types of FSS. A subgroup of children with impairing FSS
      (4.4%) was identified. These children were more likely to present
      multisymptomatic FSS than children with non-impairing FSS.   Health anxiety
      symptoms (HAS) and their associations with different physical health variables,
      including FSS, were investigated in the same population of 5-7-year-old children.
      In total, 2.4% presented prominent HAS, and the level of HAS was correlated with
      general poor health, chronic physical disease and physical complaints including
      FSS. In children with FSS, we found significant associations between the level of
      HAS and the impact of the childrens' FSS in terms of number of doctor's visits
      and missed school and/or daycare due to FSS as well as the degree of parental
      worries about the childrens' FSS. Furthermore, HAS were significantly associated
      with emotional symptoms. The findings suggest an early onset of somatisation and
      point to the need for clinical and preventive intervention in a substantial
      proportion of children. The findings also suggest a close link between HAS, FSS
      and emotional symptoms.   Medically unexplained or functional somatic symptoms
      (FSS) in children constitute a major clinical problem. However, research data on
      FSS in young children are few, and epidemiological studies are hampered by lack
      of good standardised measures.

PMID- 23171752
TI  - LUCIS: lung cancer imaging studies.
AB  - Pulmonary nodules are of high clinical importance, as they may prove to be an
      early manifestation of lung cancer. Pulmonary nodules are small, focal opacities
      that may be solitary or multiple. A solitary pulmonary nodule (SPN) is a single,
      small (= 30 mm in diameter) radiographic opacity. Larger opacities are called
      masses and are often malignant. As imaging techniques improve and more nodules
      are detected, the optimal management of SPNs remains unclear. Current strategies
      include tissue sampling or CT follow-up.  The aim of this PhD was to examine
      current non-invasive methods used to characterise pulmonary nodules and masses in
      patients with suspected lung cancer and to stage NSCLC. In doing so, this PhD
      helps to validate the existing methods used to diagnose and stage lung cancer
      correctly and, hopefully, aids in the development of new methods.  In the first
      study, 213 participants with pulmonary nodules on CT were examined with an
      additional HRCT. In this study, it was concluded that HRCT of a solitary
      pulmonary nodule, assessed using attenuation and morphological criteria is a
      fast, widely available and effective method for diagnosing lung cancer correctly,
      and especially for ruling out cancer.  In the second study, 168 patients with
      pulmonary lesions on CT were examined with an additional F-18-FDG PET/CT. It was
      concluded that when used early in the work-up of the lesions, CT raised the
      prevalence of lung cancer in the population to the point at which further
      diagnostic imaging examination could be considered redundant. Standard contrast
      enhanced CT seems better suited to identify patients with lung cancer than to
      rule out cancer. Finally, the overall diagnostic accuracy as well as the
      classification probabilities and predictive values of the two modalities were not
      significantly different. The reproducibility of the above results was
      substantial.  In the third study, 59 patients with pulmonary nodules or masses on
      chest radiography were examined with an additional DCE-CT. A qualitative as well
      as a quantitative assessment method was examined. It was concluded that although
      the results of the qualitative approach were acceptable in their own right, they
      did not, however, add anything new when compared to standard CT. The quantitative
      approach gave rise to several conclusions concerning DCE-CT analysis as well as
      the use of DCE-CT in the diagnosis of lung cancer: First, that DCE-CT is best
      analysed using logarithmic scale data transformation; second, that irrespective
      of the ROI method applied, it was not possible to discriminate malignant and
      benign; and, third, that the lack of reproducibility should be addressed. These
      results show us that DCE-CT is currently not a clinically feasible method for
      analysing pulmonary lesions. This does not necessarily mean that DCE-CT should be
      abandoned, but it does signify the need for further development of the current
      DCE-CT methods.  Finally, in the fourth study, 114 patients with NSCLC were
      examined with both a CT and with an additional F-18-FDG PET/CT. It was concluded
      that there was no significant difference in the overall diagnostic accuracy of
      the two modalities when imaging the mediastinum for staging purposes.  In
      conclusion, although standard contrast-enhanced CT has brought us far in the
      characterisation of pulmonary nodules and masses, the last decade has seen a
      constant move away from strictly anatomical approaches to imaging, towards more
      functional or analytical approaches. The desire is, of course, to be able to
      safely distinguish between malignant and benign nodules without the need for
      invasive procedures.

PMID- 23171753
TI  - Impaired physical function, loss of muscle mass and assessment of biomechanical
      properties in critical ill patients.
AB  - Intensive care unit (ICU) admission is associated with muscle weakness and ICU
      survivors report sustained limitation of physical capacity for years after
      discharge. Limited information is available on the underlying biomechanical
      properties responsible for this muscle function impairment. A plausible
      contributor to the accentuated catabolic drive in ICU patients is a synergistic
      response to inflammation and inactivity leading to loss of muscle mass. As these
      entities are predominantly present in the early phase of ICU stay, interventions
      employed during this time frame may exhibit the greatest potential to counteract
      loss of muscle mass. Despite the obvious clinical significance of muscle atrophy
      for the functional impairment observed in ICU survivors, no preventive therapies
      have been identified as yet. The overall aim of the present dissertation is to
      characterize aspects of physical function and biomechanical properties in ICU
      patients and to provide new insights into ICU-induced muscle wasting and the
      underlying biomechanical mechanisms responsible for the residual impairment of
      physical function in ICU survivors.

PMID- 23171754
TI  - Mindfulness and bodily distress.
AB  - We have created a mindfulness approach to treat patients who experience multiple,
      persistent, and disabling physical symptoms that cannot be explained by a well
      defined medical or surgical condition. Randomized controlled trials in this area
      are few, and research is hampered by the lack of clear definitions. Bodily
      distress syndrome (BDS) or bodily stress is an empirically defined definition
      unifying various conditions such as fibromyalgia, chronic fatigue syndrome, and
      somatization disorder.   In the present PhD, we explored whether patients
      suffering from BDS may be committed to mental training in the form of mindfulness
      therapy, which is a mindfulness program specifically targeted patients suffering
      from BDS.   The theoretical model for including mindfulness training in the
      treatment of BDS is based on identified neurobiological impairments in these
      patients and the neurobiological improvements that mindfulness training may
      offer. BDS is a major public health issue possibly associated with the pathology
      of the immuno-endocrine and autonomic nervous system. BDS patients are often
      stigmatized, and effective treatment is rarely delivered, which leaves these
      patients isolated, left by themselves, vulnerable to potentially harming medical
      and/or alternative treatments. Accordingly, there is a need for non-harming
      practical tools that patients can learn to master so that they can improve the
      ability to take responsibility for their own health and wellbeing.   Mindfulness
      Based Stress Reduction (MBSR) is a group program that employs mindfulness
      practice to alleviate suffering associated with physical, psychosomatic, and
      psychiatric disorders. Mindfulness-Based Cognitive Therapy (MBCT) is designed to
      prevent depressive relapse.   Paper I and II present systematic literature
      reviews only of randomized controlled trials on MBSR and MBCT. The effect of MBSR
      has been explored on fibromyalgia in three studies, none of them showed
      convincing results, but gave some indications as to improvement. The reviews
      recommended MBSR as a useful method for improving mental health; however, lack of
      long-term follow-up and active control groups are limitations in most studies.
      MBCT was recommended as a tool for preventing depressive relapse in recovered,
      recurrently depressed patients, but the implication of MBSR and MBCT is
      problematic, especially due to the lack of well educated mindfulness teachers. 
      We combined MBSR with cognitive behavioral therapy, CBT, specifically targeted
      BDS. Paper III provides original data from 119 patients enrolled in a randomized
      clinical trial, mindfulness therapy for BDS. The randomized controlled trial
      indicates that BDS patients are capable of and willing to engage in mindfulness
      therapy. This thesis showed that mindfulness therapy can safely and successfully
      engage BDS patients in mindfulness practice. Since individual CBT and psychiatric
      consultation have previously been found to have positive outcomes for BDS
      patients, we compared mindfulness therapy to an active control group entitled
      specialized treatment in which an individual treatment was planned in
      collaboration between the patient and an MD specialized in BDS, CBT, and
      psychiatry. Mindfulness therapy was comparable to specialized treatment in
      improving the quality of life and the symptoms of the patients with BDS at 15
      month follow-up.   For primary outcome physical health (PCS) at 15-month follow
      up, different developments over time for the two treatment groups could not be
      established (F(3,2674) = 1.51, p = 0.21). However, in the mindfulness therapy
      group, PCS significant changed at the end of treatment and this change remained
      at 15-month follow-up, whereas no significantly change was seen in the
      specialized treatment group until at the 15-month follow-up. In the mindfulness
      therapy group, 26%; CI: 14-38 reported a marked improvement (> 1 SD) at the end
      of treatment compared with 10%; CI: 2-18 in the specialized treatment group. This
      amounts to a statistically significant difference between the groups (OR = 3.21;
      CI 1.05-9.78, p = 0.04). The results are indicating that mindfulness therapy
      produced greater and more rapid improvements than specialized treatment.  
      Mindfulness therapy appears to produce improvements within the range of those
      reported in the STreSS-1 trial, where CBT was compared with enhanced usual care,
      and no improvements on the SF-36 scale were observed in the enhanced usual care
      group. This indicates that the changes accomplished with the two treatments
      mindfulness therapy and specialized treatment reflect real changes attributable
      to the interventions.   The economic effects of mindfulness therapy are evaluated
      in paper IV by the use of original register data from the 119 enrolled patients
      and a matched control group of 5,950 individuals. Mindfulness therapy had
      substantial socioeconomic benefits over specialized treatment. The costs incurred
      to cover permanent health-related benefits, especially disability pension, were
      significantly lower in the mindfulness therapy group than in the specialized
      treatment group over a 15-month follow-up period; 25% from the mindfulness
      therapy group received disability pension compared with 45% from the specialized
      treatment group (p = 0.025).   The total health care utilization was reduced over
      time in both groups from the year before inclusion (mean $ 5,325, median $ 2,971)
      to the year after inclusion (mean $ 3,644, median $ 1,593) (p = 0.0001). There
      was no difference between the two groups.  Five and ten years before their
      inclusion, the BDS patients were less self-supporting than an age-, gender- and
      ethnicity-matched population control group; the BDS patients accumulated more
      weeks of sickness benefit and unemployment. Thus, the included BDS patients may
      have been ill and in high risk for a social decline five and ten years before
      they received a proper diagnosis and treatment.   In conclusion, the social and
      economic consequences of BDS are significant and mindfulness therapy may have a
      potential to significantly improve function, quality of life and symptoms,
      prevent a social decline, and reduce societal costs.

PMID- 23171755
TI  - Circulating microparticles in systemic Lupus Erythematosus.
AB  - Systemic lupus erythematosus (SLE) is a systemic autoimmune disease presenting
      with a wide array of clinical manifestations and an elusive pathogenesis. A
      characteristic feature in SLE is the occurrence of autoantibodies against
      chromatin, double-stranded DNA, and RNA-binding ribonucleoproteins. Observations
      of defective clearance of dying cells in SLE combined with the generation and
      exposure of nuclear autoantigens during apoptosis have led to the hypothesis that
      improperly cleared apoptotic debris constitutes a source of autoantigens capable
      of triggering autoimmune disease. In blood, circulating, heterogeneous
      subcellular microparticles (MPs) are released from cells and platelets
      constitutively and upon cellular activation or apoptosis. Such MPs may reflect
      the state of their parental cells and tissues, and could serve as markers of
      pathology. Particular in SLE MPs may serve as carriers of autoantigens and
      constituents of immune complexes (ICs).  The purposes of this PhD thesis were to
      develop and apply qualitative and quantitative methods to characterize
      circulating MPs with respect to numbers, cellular origins and composition in a
      large cohort of well-characterized SLE patients compared to healthy and disease
      controls and to explore associations with clinical, biochemical and serological
      parameters. The PhD thesis consists of a review and three papers.  In the first
      paper we show that SLE patients have significantly decreased numbers of annexin V
      binding MPs and MPs from platelets, leukocytes and endothelial cells using flow
      cytometry. Two morphologically distinguishable populations of annexin V non
      binding MPs were increased in the SLE patients. The annexin V non-binding MPs of
      most likely cellular origin were associated with the presence of lupus nephritis,
      markers of increased disease activity and levels of endothelial cell-derived MPs.
      In the second paper we present the development of a proteomic method to
      characterize the protein composition of purified MPs using high-resolution mass
      spectrometry and establish a set of proteins which may serve as normalizers for
      MP protein quantitation enabling comparison across samples and studies. We
      identify a core proteome of more than 330 proteins in MPs from healthy
      individuals. The method enables an unbiased, comprehensive coverage of all
      proteins present in MPs irrespectively of the availability and utility of
      immunological reagents.  In the third paper we use the established flow cytometry
      and mass spectrometry platforms to show that SLE-MPs carry more surface-bound
      IgG, IgM and C1q indicating that SLE-MPs could be antigenic targets and
      constituents of ICs. Additionally, the numbers of MPs carrying IgG are also
      increased in SLE. The load of IgG on SLE-MPs was associated with markers of
      complement activation, indicators of disease activity in SLE.   In conclusion,
      using both antibody-dependent and independent methods we demonstrate that SLE-MPs
      deviate distinctly from controls and may serve as precursors of ICs associated
      with complement activation and disease activity. This supports the hypothesis of
      MPs being directly involved in or reflecting tissue-specific or systemic
      inflammation in addition to carrying accessible antigens. Accordingly, further
      characterization of the proteome and functional properties of SLE-MPs seem highly
      warranted in future studies.

PMID- 23171756
TI  - Oral health-related quality of life among parents and teachers of disabled
      schoolchildren in Kuwait.
AB  - OBJECTIVE: The objective of this study was to assess the oral health-related
      quality of life between the parents and the teachers of disabled schoolchildren
      in Kuwait. SUBJECTS AND METHODS: The three category response version of the
      General Oral Health Assessment Index (GOHAI) (12 questions, always, sometimes,
      never) was used in the questionnaires in Kuwait. Three hundred and eight (308)
      parents and 112 teachers were enrolled in this study. RESULTS: The mean age of
      the parents was 45 +/- 9.9 years and of the teachers 38 +/- 8.4 years. The mean
      GOHAI was 27.2 +/- 3.5 among the parents and 27.8 +/- 3.3 among the teachers (p =
      0.091). GOHAI was higher in the older age groups (p = 0.002) and among the
      parents with a university education (p < 0.001). GOHAI was also higher with
      increasing toothbrushing frequency among the parents (p = 0.047) and the teachers
      (p = 0.003). Altogether, 203 (66%) of the parents and 85 (76%) of the teachers
      were always able to swallow comfortably; 123 (40%) of the parents and 41 (37%) of
      the teachers were able to eat without discomfort. Overall, 132 (43%) of the
      parents and 41 (37%) of the teachers were always pleased and happy with the looks
      of their teeth and gums, or dentures. The Cronbach's alpha (0.83) indicated a
      high degree of internal consistency between different GOHAI items. CONCLUSION:
      There seemed to be no difference in the impact of oral health on the quality of
      life between the parents and the teachers of disabled schoolchildren. Oral health
      had a relatively weak impact on the quality of life of these adults.

PMID- 23171757
TI  - Efficacy of single dose of an inactivated porcine circovirus type 2 (PCV2) whole
      virus vaccine with oil adjuvant in piglets.
AB  - BACKGROUND: Post-weaning multisystemic wasting syndrome (PMWS) associated with
      PCV2 is one of the most costly diseases currently faced by the swine industry.
      The development of effective vaccines against PCV2 infection has been accepted as
      an important strategy in the prophylaxis of PMWS. METHODS: In the present study,
      a PK-15 cell-adapted formalin-inactivated prototype vaccine candidate was
      prepared using a strain of PCV2 from China. Inactivation of the virus was
      accomplished using a standard formalin inactivation protocol. The protective
      properties of the inactivated PCV2 vaccine were evaluated in piglets. Ten 28-day
      old pigs were randomly assigned to two groups, each with five. Group 1 was
      vaccinated intramuscularly with the inactivated virus preparation; Group 2
      received sterile PBS as a placebo. By 28 days post-vaccination (DPV), Groups 1
      and 2 were challenged intranasally and intramuscularly with 5 * 107 TCID50 of a
      virulent PCV2 isolate. RESULTS: The vaccinated pigs seroconverted to PCV2 and had
      high levels of serum antibodies to PCV2 at 28 days after vaccination, whereas the
      control pigs remained seronegative. No significant signs of clinical disease were
      recorded following the challenge with PCV2, but moderate amounts of PCV2 antigen
      were detected in most lymphoid organs of the control pigs. PCV2 was detected in
      two out of the five vaccinated pigs. Furthermore, pathological lesions and
      viremia were milder in the vaccinated group. CONCLUSIONS: The obtained results
      indicate that the inactivated PCV2 virus vaccine with an oil adjuvant induce an
      immunological response in pigs that appears to provide protection from infection
      with PCV2. The vaccine, therefore, may have the potential to serve as a vaccine
      aimed to protect pigs from developing PMWS.

PMID- 23171758
TI  - Attitudes, beliefs and perceptions regarding truth disclosure of cancer-related
      information in the Middle East: a review.
AB  - The aim of this review is to evaluate the current status concerning attitudes,
      beliefs and/or practices of patients, family members, health professionals and/or
      caregivers regarding truth disclosure about a cancer diagnosis in the Greater
      Middle East countries. A search was done via MedLine for all publications related
      to this review objective. 55 publications were included emanating from Egypt,
      Iran, Israel, Jordan, Kuwait, Lebanon, Palestine Pakistan, Saudi Arabia, Turkey,
      and United Arab Emirates. In the Greater Middle East region, a diagnosis of
      cancer is still mixed with social stigma and misperceptions related to
      incurability. Physicians conserve a truth disclosure policy in which from one
      side they respect some of the historical and cultural misperceptions about cancer
      and accordingly, tell the truth about cancer to one of the family members and
      from another side acknowledge the patients' right to know the truth and tend to
      disclose it for him(or her) when possible. Family members and caregivers'
      attitudes, perceptions and beliefs about telling the truth to the patient seem to
      be in favor of concealment. Discrepant results concerning physicians' and
      patients' evaluation of the quality of truth disclosure exist in the literature.
      Education programs in breaking bad news are lacking in many countries. Finally,
      the most important and common problem affecting truth disclosure to a patient
      suffering from cancer is the lack of codes and legislations concerning the
      patients' rights in an informed consent. Studies, legislations and training
      programs are needed in this domain in Middle Eastern societies.

PMID- 23171759
TI  - Fixing the leak: targeting the vascular endothelium in sepsis.
AB  - Angiopoietin-1 is a Tie-2 receptor agonist that stabilizes vascular endothelium,
      promoting endothelial maturation and preventing capillary leak. Angiopoietin-2 is
      largely a competitive partial antagonist that is markedly elevated in humans and
      animal models of sepsis and other inflammatory states, directly disrupts the
      endothelial barrier, and has been correlated with end-organ dysfunction and death
      in sepsis. In the previous issue of Critical Care, Alfieri and colleagues used
      intravital microscopy to study the microvasculature in a murine model of sepsis.
      Treatment with a modified angiopoietin-1 molecule led to reversal of albumin
      vascular leak and improved blood flow to skeletal muscle, as well as a decrease
      in the levels of several inflammatory cytokines. Importantly, the angiopoietin-1
      variant was administered 20 hours after initial lipopolysaccharide challenge.
      This study adds to the evidence that the angiopoietin/Tie-2 axis represents a
      modifiable pathway through which targeted therapy may be able to directly reverse
      part of the pathology of sepsis. 

PMID- 23171761
TI  - Leptospirosis, diagnostic challenges, American Samoa.

PMID- 23171760
TI  - Mediator regulates non-coding RNA transcription at fission yeast centromeres.
AB  - BACKGROUND: In fission yeast, centromeric heterochromatin is necessary for the
      fidelity of chromosome segregation. Propagation of heterochromatin in dividing
      cells requires RNA interference (RNAi) and transcription of centromeric repeats
      by RNA polymerase II during the S phase of the cell cycle. RESULTS: We found that
      the Med8-Med18-Med20 submodule of the Mediator complex is required for the
      transcriptional regulation of native centromeric dh and dg repeats and for the
      silencing of reporter genes inserted in centromeric heterochromatin. Mutations in
      the Med8-Med18-Med20 submodule did not alter Mediator occupancy at centromeres;
      however, they led to an increased recruitment of RNA polymerase II to centromeres
      and reduced levels of centromeric H3K9 methylation accounting for the centromeric
      desilencing. Further, we observed that Med18 and Med20 were required for
      efficient processing of dh transcripts into siRNA. Consistent with defects in
      centromeric heterochromatin, cells lacking Med18 or Med20 displayed elevated
      rates of mitotic chromosome loss. CONCLUSIONS: Our data demonstrate a role for
      the Med8-Med18-Med20 Mediator submodule in the regulation of non-coding RNA
      transcription at Schizosaccharomyces pombe centromeres. In wild-type cells this
      submodule limits RNA polymerase II access to the heterochromatic DNA of the
      centromeres. Additionally, the submodule may act as an assembly platform for the
      RNAi machinery or regulate the activity of the RNAi pathway. Consequently, Med8
      Med18-Med20 is required for silencing of centromeres and proper mitotic
      chromosome segregation.

PMID- 23171762
TI  - Evaluation of matrix-assisted laser desorption/ionization time of flight mass
      spectrometry for the identification of ceratopogonid and culicid larvae.
AB  - Matrix-assisted laser desorption/ionization time of flight mass spectrometry
      (MALDI-TOF MS) was evaluated for the rapid identification of ceratopogonid
      larvae. Optimal sample preparation as evaluated with laboratory-reared biting
      midges Culicoides nubeculosus was the homogenization of gut-less larvae in 10%
      formic acid, and analysis of 0.2 mg/ml crude protein homogenate mixed with SA
      matrix at a ratio of 1:1.5. Using 5 larvae each of 4 ceratopogonid species (C.
      nubeculosus, C. obsoletus, C. decor, and Dasyhelea sp.) and of 2 culicid species
      (Aedes aegypti, Ae. japonicus), biomarker mass sets between 27 and 33 masses were
      determined. In a validation study, 67 larvae belonging to the target species were
      correctly identified by automated database-based identification (91%) or manual
      full comparison (9%). Four specimens of non-target species did not yield
      identification. As anticipated for holometabolous insects, the biomarker mass
      sets of adults cannot be used for the identification of larvae, and vice versa,
      because they share only very few similar masses as shown for C. nubeculosus, C.
      obsoletus, and Ae. japonicus. Thus, protein profiling by MALDI-TOF as a quick,
      inexpensive and accurate alternative tool is applicable to identify insect larvae
      of vector species collected in the field.

PMID- 23171763
TI  - Epizootic spread of Schmallenberg virus among wild cervids, Belgium, Fall 2011.
AB  - Schmallenberg virus was detected in cattle and sheep in northwestern Europe in
      2011. To determine whether wild ruminants are also susceptible, we measured
      antibody seroprevalence in cervids (roe deer and red deer) in Belgium in 2010 and
      2011. Findings indicated rapid spread among these deer since virus emergence ~250
      km away.

PMID- 23171765
TI  - [Non-contrast magnetic resonance angiography for renal arteries using breath held
      inflow inversion recovery-fan shaped inward outward view ordering: impact on
      image quality by changing wait recovery time after data acquisition].
AB  - PURPOSE: We assessed the wait time of non-contrast renal artery magnetic
      resonance (MR) angiography with a single breath hold using inflow inversion
      recovery-fan shaped inward outward view ordering technique in normal volunteers.
      METHODS: The wait time (WT)-the duration between the data acquisition and the
      following inversion recovery pulse-was varied from 10 ms to 2000 ms, and the
      contrast ratio between the renal artery and the background structures for each WT
      was assessed quantitatively. A simulation was also performed. RESULTS: The
      contrast ratio between the renal artery and each background structure with 2000
      ms of WT was higher than that with 10 ms of WT. The contrast ratio between the
      renal artery and renal cortex with 1500 ms of WT was also higher than that with
      10 ms of WT. In the simulation, when WT lengthened, the residual longitudinal
      magnetization of each background structure lowered. CONCLUSION: The WT affects
      contrast; adjustment of WT should be added to the assessment of the imaging
      parameter.

PMID- 23171766
TI  - [Questions that radiography students have regarding X-ray photography: a
      qualitative study].
AB  - OBJECTIVE: To improve lectures and training programs on X-ray photography, we
      aimed to determine the questions that radiography students have regarding X-ray
      photography. METHODS: We collected text data from questions on X-ray photography
      in radiography student reports after an X-ray photography training program. The
      text data were analyzed using content analysis. Codes were assigned to segments
      and they were categorized according to similarities. RESULTS: From 111 reports,
      348 questions were collected. Four categories and 47 subcategories were obtained.
      The "Required Knowledge" category comprised subcategories concerning knowledge
      for the X-ray photography including X-ray radiography methodology and disease
      knowledge. The "Radiography Service" category comprised subcategories concerning
      radiographers' responsibilities in a hospital including the role of radiographer
      and the extent of responsibilities. The "Radiographers' Challenges" category
      comprised subcategories concerning unusual situations radiographers encounter at
      work including accurate positioning and communication with patients. The "Patient
      Types" category comprised subcategories concerning patients in whom X-ray
      photography was considered difficult including pediatric patients and patients
      with serious conditions. Questions related to subcategories in "Radiographers'
      Challenges" and "Patient Types" were interrelated. Radiography students had
      concerns regarding whether they would be able to handle difficult patients
      efficiently in clinical situations. CONCLUSION: We were able to suggest the re
      orientation of radiography education according to students' intellectual appetite
      regarding X-ray radiography.

PMID- 23171767
TI  - [Slice profile measurement using a crossed thin-ramps method in three-dimensional
      magnetic resonance imaging].
AB  - Recent progress in variable-flip-angle fast spin-echo technology has further
      extended the utility of three-dimensional (3D) magnetic resonance imaging (MRI)
      for clinical application. The slice profile in 3D MRI is the point spread
      function that has a sync form in principle, whereas a slice profile in 2D imaging
      provides information on characteristics of selective radio frequency excitation.
      We investigated the optimal condition to measure 3D slice profiles using a
      crossed thin-ramps phantom. We found that the profile data should cover a large
      area in order to evaluate both the main lobe and side lobes in the slice profile,
      and that the appropriate slice thickness was 2 mm. We also found that artifacts
      in the direction perpendicular to the slice create an offset error in the
      measured slice profile when 3D imaging. In this paper, we describe the optimal
      condition and some remarks on the slice profile evaluation for 3D MRI.

PMID- 23171768
TI  - [Estimation of activities caused by black spots in digital radiography systems:
      analysis of black spots by the low concentrate radioisotopes adhered directly to
      the surface of the phosphor plate].
AB  - Because of an accident of the nuclear power plants in the Fukushima, many
      radioisotopes (RI) have been diffused to the environment. As a result, black
      spots were appearing on the medical images which were taken by the phosphor
      plate. The aim of this study is to evaluate the activity (Bq) of radioactive
      contaminated IP based on the experiment using RI. The radioactive material
      ((134)Cs and/or (137)Cs) in the form of liquid was dropped on filter paper (25
      mm(2)), and radioactive sources having 40-240 Bq activities were made. These
      sources were closely attached to the IP with irradiation times of 2-22 h. Then,
      we obtained the relationship between pixel values and products of activities and
      irradiation times. Using these relationships, we evaluated the activity in the
      contaminated IP. The evaluated value of approximately 7 Bq was in good agreement
      with a value which was inhered in a chemical wiper used for the decontamination
      of the IP. Based on the results, we summarized that almost all black spots were
      created by the RI adhered directly to the IP.

PMID- 23171769
TI  - [Development of a computer-aided diagnosis system for the distinction between
      benign and malignant gastric lesions].
AB  - We proposed a method for a computer-aided diagnosis system that distinguishes
      between benign and malignant lesions in gastrointestinal digital radiography. To
      begin with, the level set method was applied in order to extract a tumor region
      from the image which was smoothed by the bilateral filter. Next, we selected four
      image features with the large SN ratio among various image features obtained from
      a tumor region using the Mahalanobis-Taguchi method, which has been employed
      mainly in quality engineering. The selected four image features-circularity,
      irregularity, size, and perimeter-were used as input data for the artificial
      neural network, which was employed for distinction between benign and malignant
      lesions. By using 43 regions of interest cropped from the 43 clinical cases, the
      area under the ROC curve (AUC) of diagnostic accuracy for the classification
      obtained with this proposed method was 0.970, whereas the average AUC obtained
      with 7 human observers (3 radiologists and 4 radiological technologist) was
      0.941.

PMID- 23171770
TI  - [Positional accuracy and quality assurance of Backup JAWs required for volumetric
      modulated arc therapy].
AB  - The tolerance of the Backup diaphragm (Backup JAW) setting in Elekta linac was
      specified as 2 mm according to the AAPM TG-142 report. However, the tolerance and
      the quality assurance procedure for volumetric modulated arc therapy (VMAT) was
      not provided. This paper describes positional accuracy and quality assurance
      procedure of the Backup JAWs required for VMAT. It was found that a gap-width
      error of the Backup JAW by a sliding window test needed to be less than 1.5 mm
      for prostate VMAT delivery. It was also confirmed that the gap-widths had been
      maintained with an error of 0.2 mm during the past one year.

PMID- 23171771
TI  - [Practical method for six-dimensional online correction system with image guided
      radiation therapy].
AB  - In this study, we developed a correction method for coordinate transformation
      errors that are produced in combination with the ExacTrac X-ray system (BrainLAB)
      and HexaPOD (Elekta) in image guided radiation therapy (IGRT). The positional
      accuracy of the correction method was compared between the ExacTrac Robotics
      (BrainLAB) and no correction. We tried to correct iBeam evo couch top (Elekta) by
      operating two steps drive like ExacTrac Robotics. No correction for HexaPOD
      showed a maximal error of 4.52 mm, and the couch did not move to the correct
      position. However, our correction method for HexaPOD showed the positional
      accuracy within 1 mm. Our method has no significant difference with ExacTrac
      Robotics (paired t-test, P>0.1). But, when the correction values for the rotatory
      directions were large, the positional accuracy tended to be poor. The smallest
      setup errors for the rotatory directions are important for IGRT.

PMID- 23171772
TI  - [Method for evaluating the mechanical isocenter of the gantry of a radiotherapy
      machine with motion picture trace analysis software].
AB  - In recent years, development of advanced radiotherapy technology has resulted in
      an improvement in radiotherapy. Although the radiotherapy system has improved,
      the effect of the gap, the gyration center, and distortion of the rotation orbit
      cannot be neglected. Therefore, a verification method for a geometrical isocenter
      and rotation orbit in a three-dimension (3D) space is required. We developed a
      verification method for determination of the geometrical isocenter. In this
      method, the rotation of the gantry that applied the measured target from two
      directions was imaged and analyzed using animation pursuit analysis software. The
      measurement targets were pursued by analysis, and the rotation orbit of the
      target was visually evaluated from obtained coordinates and displacement
      distance. The gyration center in 3D space was calculated from pursued coordinates
      and compared with the intersection in the side laser and crosshair. In this
      verification method, the rotation orbit and geometrical isocenter in the 3D space
      were confirmed, and visually evaluated. Thus, this method was effective in
      verifying the geometrical isocenter by solving the problem of the measurement
      precision and reproducibility.

PMID- 23171773
TI  - [Characteristic of the image by image reconstruction method applied to successive
      approximation method].
AB  - In recent years, an applied successive approximation method has emerged as a new
      reconstruction technique of the computed tomography (CT). The CT unit of our
      hospital is equipped with an adaptive statistical iterative reconstruction (ASiR)
      which applies this method. This time, we have investigated the feature of the
      images through the ASiR. A subtraction of the filtered back projection (FBP)
      image from the ASiR image of various phantoms took place, and the structure
      marginal region was evaluated by varying the blend rate of ASiR and the display
      field of view (DFOV). By varying the CT value difference with the surroundings
      (using iodinated contrast medium) the structure marginal region of the
      subtraction image was evaluated. Modulation transfer function (MTF) and noise
      power spectrum (NPS) measurements were carried out to make evaluations. The
      result was that the CT value of the marginal unit structure was elevated with an
      increase of the blend ratio of ASiR and DFOV. When the CT value difference with
      surroundings was high, an edge was formed in the structure near the marginal
      region, and when it was low, a slowdown in the peripheral zone was observed. The
      value of MTF and NPS showed the change. The formation of the edge and slowdown in
      the peripheral zone can be seen in clinical images, we fully need to understand
      this result and make use of it in the clinical field.

PMID- 23171774
TI  - [Quality assurance of respiratory-gated stereotactic body radiation therapy in
      lung using real-time position management system].
AB  - In this study, we investigated comprehensive quality assurance (QA) for
      respiratory-gated stereotactic body radiation therapy (SBRT) in the lungs using a
      real-time position management system (RPM). By using the phantom study, we
      evaluated dose liberality and reproducibility, and dose distributions for low
      monitor unite (MU), and also checked the absorbed dose at isocenter and dose
      profiles for the respiratory-gated exposure using RPM. Furthermore, we evaluated
      isocenter dose and dose distributions for respiratory-gated SBRT plans in the
      lungs using RPM. The maximum errors for the dose liberality were 4% for 2 MU, 1%
      for 4-10 MU, and 0.5% for 15 MU and 20 MU. The dose reproducibility was 2% for 1
      MU and within 0.1% for 5 MU or greater. The accuracy for dose distributions was
      within 2% for 2 MU or greater. The dose error along a central axis for
      respiratory cycles of 2, 4, and 6 sec was within 1%. As for geometric accuracy,
      90% and 50% isodose areas for the respiratory-gated exposure became almost 1 mm
      and 2 mm larger than without gating, respectively. For clinical lung-SBRT plans,
      the point dose at isocenter agreed within 2.1% with treatment planning system
      (TPS). And the pass rates of all plans for TPS were more than 96% in the gamma
      analysis (3 mm/3%). The geometrical accuracy and the dose accuracy of TPS
      calculation algorithm are more important for the dose evaluation at penumbra
      region for respiratory-gated SBRT in lung using RPM.

PMID- 23171775
TI  - [Non-contrast time-resolved magnetic resonance angiography combining high
      resolution multiple phase echo planar imaging based signal targeting and
      alternating radiofrequency contrast inherent inflow enhanced multi phase
      angiography combining spatial resolution echo planar imaging based signal
      targeting and alternating radiofrequency in intracranial arteries].
AB  - Detailed information on anatomy and hemodynamics in cerebrovascular disorders
      such as AVM and Moyamoya disease is mandatory for defined diagnosis and treatment
      planning. Arterial spin labeling technique has come to be applied to magnetic
      resonance angiography (MRA) and perfusion imaging in recent years. However, those
      non-contrast techniques are mostly limited to single frame images. Recently we
      have proposed a non-contrast time-resolved MRA technique termed contrast inherent
      inflow enhanced multi phase angiography combining spatial resolution echo planar
      imaging based signal targeting and alternating radiofrequency (CINEMA-STAR).
      CINEMA-STAR can extract the blood flow in the major intracranial arteries at an
      interval of 70 ms and thus permits us to observe vascular construction in full by
      preparing MIP images of axial acquisitions with high spatial resolution. This
      preliminary study demonstrates the usefulness of the CINEMA-STAR technique in
      evaluating the cerebral vasculature.

PMID- 23171776
TI  - [Approach to the core of explanation of radiation exposure].

PMID- 23171777
TI  - [Key technology of photon-counting mammography].

PMID- 23171782
TI  - Please don't call me RI anymore; I may not be the one you think I am!
AB  - The previous issue of Critical Care reports new data on renal resistive index in
      critically ill patients. Although high renal resistive index may indeed be
      associated with acute kidney injury, the existence of several determinants of
      this index, of which renal resistance is only one among many, obscures the
      usefulness of this index in clinical practice. 

PMID- 23171783
TI  - The Israel Cancer Association's role as a volunteer organization in forecasting,
      establishing, implementing and upgrading palliative care services in Israel.
AB  - The Israel Cancer Association has contributed, as a key player, to the
      establishment and upgrade of palliative care in Israel. The aim of this article
      is to describe the involvement and contribution of the ICA, as a volunteer
      organization, from a clinical, educational, legal, and organizational
      perspective. Another main goal of this survey is to shed light on the palliative
      care network in Israel, in each one of these infrastructures.

PMID- 23171785
TI  - [Remember pregnant women during the seasonal influenza vaccination].

PMID- 23171784
TI  - Catecholamines can induce pulmonary remodeling in rats.
AB  - BACKGROUND/AIMS: Previously, we found that catecholamine (CA) infusion in rats
      induced pulmonary injury with edema and inflammation resembling acute lung injury
      in humans. Here, we examined effects of norepinephrine (NE) and of selective
      alpha- and beta-adrenergic agonists on the remodeling of pulmonary extracellular
      matrix. METHODS: Eighty rats were infused over 8-72 h with NE, phenylephrine
      (PE), isoproterenol (ISO) or NaCl solution. We investigated mRNA expression of
      collagen, matrix metalloproteinase (MMP)-2, its tissue inhibitor (TIMP-2) and
      transforming growth factor (TGF)-beta isoforms in lung tissue. Additionally, lung
      histology, hemodynamic function and cardiac hypertrophy were evaluated. RESULTS:
      After 72 h of infusion, lung histology showed beginning fibrosis and vascular
      hypertrophy. Collagen type I, MMP-2 and TIMP-2 mRNA expression were significantly
      elevated. All these effects were most pronounced with NE while PE and ISO induced
      weaker responses. TGF-beta mRNA expression was also elevated after 72 h,
      predominantly after PE infusion. Cardiac hypertrophy was most pronounced after
      ISO infusion. CONCLUSION: CA infusion over 72 h may induce pulmonary remodeling.
      Mainly alpha-adrenergic but also beta-adrenergic mechanisms contribute to these
      processes. In contrast, cardiac hypertrophy is predominantly mediated by beta
      adrenergic stimulation and hence, is considered to be a direct adrenergic effect
      rather than a consequence of pulmonary fibrosis.

PMID- 23171786
TI  - ["There are no bones in osteoporosis"].

PMID- 23171787
TI  - [Report: complicated influenza A(H1N1) in a second-trimester pregnancy].
AB  - A 27-year-old woman at 25 weeks of gestation was admitted to hospital due to
      bilateral pneumonia with increasing hypoxia. She was tested positive for
      influenza A (H1N1) and successfully treated with oral oseltamivir. Nine days
      after the admission pathological umbilical flows were recorded and an emergency
      caesarean was performed at 26 weeks + 2 days of gestation. The neonatal period
      was uncomplicated. Influenza A (H1N1) is especially dangerous in pregnant women
      and vaccination is important.

PMID- 23171788
TI  - [Diagnosing and treating osteoporosis in patients with chronic obstructive
      pulmonary disease].
AB  - Patients with chronic obstructive pulmonary disease have a high risk of
      osteoporosis and fractures. We present an algorithm for the prevention and
      treatment of osteoporosis in patients with chronic obstructive pulmonary disease.

PMID- 23171789
TI  - [Medical therapy of osteoporosis in patients with mildly to moderate decreased
      renal function].
AB  - Both chronic kidney disease and osteoporosis are frequent conditions in the
      general population. Most drugs for treating osteoporosis seem safe in terms of
      affecting renal function for patients with mildly to moderate decreased renal
      function. There are very few data on the efficacy (reduction in fracture risk) or
      safety in patients with severely decreased renal function (glomerular filtration
      rate < 30 ml/min) or on dialysis.

PMID- 23171790
TI  - [Treatment of mineral bone disorder with pharmaceuticals which influence the
      calcium phosphor turnover].
AB  - This review discusses the mineral bone disorders in patients with chronic kidney
      disease. We focus on the management of these conditions by administration of
      calcium, vitamin D (ergocalciferol and cholecalciferol), vitamin D receptor
      activators (calcitriol, alphacalcidiol), phosphate binders and calcimimetics
      (cinacalcet).

PMID- 23171791
TI  - [Otomicroscopy].

PMID- 23171792
TI  - [Preferences for user fees in general practice and the establishment of general
      practitioners in rural areas].
AB  - This study elicits the preferences of general practitioners (GPs) and patients
      for different ways of mitigating problems with a general and structural lack of
      GPs in Denmark. The supply of GPs can be increased in rural areas if the GPs are
      compensated (approximately 470,000 DKK per year in extra surplus) and if other
      non-pecuniary factors are implemented. The study further showed that there was a
      positive willingness to pay for a consultation (74-85 DKK), although the majority
      of the GPs do not support this initiative.

PMID- 23171793
TI  - [Hydrops foetalis caused by a mediastinal teratoma].
AB  - Hydrops foetalis (HF) is defined as an accumulation of fluid in at least two
      compartments of the body, e.g. the subcutis, the pleural cavities, the
      pericardial cavity and the abdomen. In present time, non-immune causes, including
      tumours, predominate. We present a case of severe HF, caused by a mass which was
      clinically interpreted as a hernia of the diaphragm at gestational week 19 + 6.
      An abortion was granted and performed. Autopsy revealed an immature teratoma in
      the mediastinum compressing the heart and airway. The prognosis and treatment of
      mediastinal teratoma and HF is discussed.

PMID- 23171794
TI  - [Vasa Previa].

PMID- 23171795
TI  - MicroRNAs reprogram normal fibroblasts into cancer-associated fibroblasts in
      ovarian cancer.
AB  - Cancer-associated fibroblasts (CAF) are a major constituent of the tumor stroma,
      but little is known about how cancer cells transform normal fibroblasts into
      CAFs. microRNAs (miRNA) are small noncoding RNA molecules that negatively
      regulate gene expression at a posttranscriptional level. Although it is clearly
      established that miRNAs are deregulated in human cancers, it is not known whether
      miRNA expression in resident fibroblasts is affected by their interaction with
      cancer cells. We found that in ovarian CAFs, miR-31 and miR-214 were
      downregulated, whereas miR-155 was upregulated when compared with normal or tumor
      adjacent fibroblasts. Mimicking this deregulation by transfecting miRNAs and
      miRNA inhibitors induced a functional conversion of normal fibroblasts into CAFs,
      and the reverse experiment resulted in the reversion of CAFs into normal
      fibroblasts. The miRNA-reprogrammed normal fibroblasts and patient-derived CAFs
      shared a large number of upregulated genes highly enriched in chemokines, which
      are known to be important for CAF function. The most highly upregulated
      chemokine, CCL5, (C-C motif ligand 5) was found to be a direct target of miR-214.
      These results indicate that ovarian cancer cells reprogram fibroblasts to become
      CAFs through the action of miRNAs. Targeting these miRNAs in stromal cells could
      have therapeutic benefit. SIGNIFICANCE: The mechanism by which quiescent
      fibroblasts are converted into CAFs is unclear. The present study identifies a
      set of 3 miRNAs that reprogram normal fibroblasts to CAFs. These miRNAs may
      represent novel therapeutic targets in the tumor microenvironment.

PMID- 23171797
TI  - A new international presence in interventional cardiology.

PMID- 23171798
TI  - Evolution and future perspectives for cardiovascular interventions in China.

PMID- 23171796
TI  - Elucidating distinct roles for NF1 in melanomagenesis.
AB  - BRAF mutations play a well-established role in melanomagenesis; however, without
      additional genetic alterations, tumor development is restricted by oncogene
      induced senescence (OIS). Here, we show that mutations in the NF1 tumor
      suppressor gene cooperate with BRAF mutations in melanomagenesis by preventing
      OIS. In a genetically engineered mouse model, Nf1 mutations suppress Braf-induced
      senescence, promote melanocyte hyperproliferation, and enhance melanoma
      development. Nf1 mutations function by deregulating both phosphoinositide 3
      kinase and extracellular signal-regulated kinase pathways. As such, Nf1/Braf
      mutant tumors are resistant to BRAF inhibitors but are sensitive to combined
      inhibition of mitogen-activated protein/extracellular signal-regulated kinase
      kinase and mTOR. Importantly, NF1 is mutated or suppressed in human melanomas
      that harbor concurrent BRAF mutations, NF1 ablation decreases the sensitivity of
      melanoma cell lines to BRAF inhibitors, and NF1 is lost in tumors from patients
      following treatment with these agents. Collectively, these studies provide
      mechanistic insight into how NF1 cooperates with BRAF mutations in melanoma and
      show that NF1/neurofibromin inactivation may have an impact on responses to
      targeted therapies.

PMID- 23171799
TI  - Europe, China and the world: the EAPCI international membership.

PMID- 23171800
TI  - Nine-month angiographic and 2-year clinical follow-up of the NOYA biodegradable
      polymer sirolimus-eluting stent in the treatment of patients with de novo native
      coronary artery lesions: the NOYA I trial.
AB  - AIMS: This study sought to evaluate the safety and efficacy of the NOYA stent
      which is a cobalt chromium-based sirolimus-eluting stent (SES) with DL
      polylactide biodegradable polymer (Medfavour Medical, Beijing, China) in treating
      de novo coronary artery lesions. METHODS AND RESULTS: The NOYA I trial was
      designed to compare the NOYA stent with the FIREBIRD2TM stent, a durable polymer
      SES widely used in China (MicroPort Medical, Shanghai, China); the trial was a
      non-inferiority trial with a primary angiographic endpoint of the in-stent late
      lumen loss (LLL) at nine-month follow-up. The secondary endpoints were binary
      restenosis rates within nine months, major adverse cardiac events (MACE) defined
      as the composite of cardiac death, myocardial infarction (MI) or target lesion
      revascularisation (TLR), and definite/probable stent thrombosis (ST) at 24-month
      follow-up. A total of 300 patients (n=150 in each group) were enrolled in the
      study from 16 Chinese centres. The LLL in the NOYA group at nine-month follow-up
      was similar to the FIREBIRD2 group (0.11+/-0.18 mm vs. 0.14+/-0.23 mm, p=0.16;
      non-inferiority p<0.001). The rates of MACE, death, MI and TLR at 24-month follow
      up were comparable between these two devices (p>0.05, respectively). CONCLUSIONS:
      The biodegradable polymer NOYA stent was non-inferior to the FIREBIRD2 durable
      polymer stent with respect to the primary non-inferiority endpoint of in-stent
      LLL at nine-month follow-up. Clinical outcomes at 24-month follow-up were
      comparable between the two stents. (ClinicalTrials.gov number, NCT01226355).

PMID- 23171801
TI  - Five-year clinical follow-up of unprotected left main bifurcation lesion
      stenting: one-stent versus two-stent techniques versus double-kissing crush
      technique.
AB  - AIMS: The present study aimed to compare the long-term (five-year) safety and
      efficacy between the one-stent, two-stent and double-kissing (DK) crush
      strategies, utilising drug-eluting stents, for unprotected left main coronary
      artery (ULMCA) bifurcation lesions. METHODS AND RESULTS: Between March 2004 and
      April 2007, 633 consecutive patients with ULMCA bifurcation lesions (232 in the
      one-stent group and 401 in the two-stent group) were prospectively enrolled. The
      primary endpoint was the occurrence of major adverse cardiac events (MACE), a
      composite of cardiac death, myocardial infarction (MI), and target vessel
      revascularisation (TVR), at five-year follow-up. Patients in the the two-stent
      group were classified as DK crush (n=155) and other two-stent techniques
      (culotte, T-stenting, kissing stenting and classical crush, n=246). Forty-seven
      (16.8%) patients in the one-stent group crossed over to the two-stent group. The
      one-stent group was associated with an increased incidence of MI compared to the
      two-stent approach (10.5% vs. 5.5%, p=0.025). The crude rate of MACE at five
      years was 28.0% in the one-stent group and 28.4% in the two-stent group
      (p=0.927). DK crush was associated with a significantly decreased five-year MACE
      compared to the other two-stent approaches or the one-stent approach (DK crush:
      14.8% vs. other two-stent approaches: 37.0%, one-stent approach: 28.0%, p<0.001).
      The main benefit of DK crush primarily appeared to be secondary to a reduction in
      TVR (7.7% vs. 30.5% vs. 18.1%, p<0.001). By Cox regression analyses, the non-DK
      crush two-stent technique, a high SYNTAX Score (>=33) or New Risk Stratification
      (NERS) score (>20), and incomplete revascularisation were shown to be independent
      predictors of MACE at five-year follow-up. CONCLUSIONS: With distal left main
      true bifurcations, the two-stent technique (excluding DK crush) is an independent
      predictor of long-term MACE. DK crush is associated with more favourable long
      term clinical outcomes. Confirmation of these findings is required from
      randomised controlled trials.

PMID- 23171802
TI  - A new generation of biodegradable polymer-coated sirolimus-eluting stents for the
      treatment of coronary artery disease: final 5-year clinical outcomes from the
      CREATE study.
AB  - AIMS: The aim of the present study was to evaluate the five-year safety and
      efficacy of a biodegradable polymer-coated sirolimus-eluting stent with six
      months dual antiplatelet therapy in daily practice. METHODS AND RESULTS: Two
      thousand and seventy-seven daily practice patients, exclusively treated with
      biodegradable polymer-coated sirolimus-eluting stents (EXCEL; JW Medical Systems,
      Weihai, China), were prospectively enrolled in the multicentre CREATE study.
      Clinical follow-up was completed in 1,982 patients (95.4%) at five-year follow
      up. The rates of cardiac death, non-fatal myocardial infarction (MI), target
      lesion revascularisation and overall major adverse cardiac events (MACE) at five
      year follow-up were 3.0%, 1.5%, 3.7% and 7.4%, respectively. The rates of
      definite or probable stent thrombosis (ST) at five years and definite ST from one
      to five years were 1.1% and 0.3%, respectively. Heart failure (hazard ratio [HR]:
      3.324, 95% confidence interval [CI]: 1.729-6.391, p<0.001) and prior MI (HR:
      2.664, 95% CI: 1.358-5.227, p=0.004) were independent predictors of ST. Landmark
      analysis of a propensity score matched patient cohort showed that patients with
      or without clopidogrel treatment after six months had similar clinical outcomes.
      CONCLUSIONS: The present study demonstrates satisfactory and sustained five-year
      clinical safety and efficacy profiles as evidenced by the low rates of MACE and
      ST for the EXCEL, a biodegradable polymer-based sirolimus-eluting stent, when
      patients were treated with six months dual antiplatelet therapy in daily
      practice.

PMID- 23171803
TI  - Sodium bicarbonate plus N-acetylcysteine to prevent contrast-induced nephropathy
      in primary and rescue percutaneous coronary interventions: the BINARIO
      (BIcarbonato e N-Acetil-cisteina nell'infaRto mIocardico acutO) study.
AB  - AIMS: Contrast-induced nephropathy (CIN) is a frequent and potentially harmful
      complication of percutaneous coronary interventions (PCI), especially in the
      setting of ST-elevation myocardial infarction (STEMI). We tested the efficacy of
      a sodium bicarbonate (SB)-based hydration in urgent PCI for STEMI. METHODS AND
      RESULTS: From June 2009 to September 2010, 262 consecutive STEMI patients
      undergoing urgent PCI were prospectively enrolled and treated by SB-based
      hydration (154 mEq/L at 3 ml Kg-1 for one hour followed by 1 ml Kg-1 for six
      hours) (group A). As controls, 262 consecutive STEMI patients receiving 0.9%
      saline hydration (1 ml Kg-1 for 24 hours) before June 2009 were retrospectively
      enrolled (group B). Both groups received high-dose N-acetylcysteine (NAC). The
      primary endpoint was the composite of in-hospital death, need for dialysis and
      CIN (>=25% increase in serum creatinine at 48 hours). The two groups were
      comparable for baseline clinical and procedural characteristics, for Mehran risk
      score and baseline estimated glomerular filtration rate. The primary combined
      endpoint was significantly reduced in group A as compared to group B (9.2 vs.
      18.7%, p=0.023) with a number needed to treat (NNT) of 11. Specifically, a
      significant reduction of both in-hospital death (2.3 vs. 6.1%, p=0.049, NNT 27)
      and CIN (8.0 vs. 14.1%, p=0.03, NNT 17) was observed, with no difference in the
      need for dialysis. CONCLUSIONS: Our data indicate that hydration with sodium
      bicarbonate in addition to high-dose NAC in the setting of urgent PCI for STEMI
      is associated with a net clinical benefit.

PMID- 23171804
TI  - The utility of a 5-in-6 double catheter technique in treating complex coronary
      lesions via transradial approach: the DOCA-TRI study.
AB  - AIMS: To evaluate the efficacy and safety of a 5-in-6 double catheter (DC)
      technique during transradial complex PCI compared to a conventional buddy-wire or
      balloon-anchoring approach. METHODS AND RESULTS: One hundred and eighty-seven
      patients who failed in stent or balloon delivery after successful wiring of the
      target vessel were prospectively randomised to further treatment with a 5-in-6 DC
      technique (DC group, n=94) or by a conventional buddy-wire or balloon-anchoring
      approach (control group, n=93). Baseline clinical and lesion features were
      comparable between the two groups. The primary endpoint of technical success was
      significantly higher in the DC than in the control group (97.9% and 39.8%,
      p<0.001). Fifty-six patients (60.2%) in the control group with failure of the
      buddy-wire or balloon-anchoring approach achieved successful PCI with bailout use
      of a DC technique. Procedural x-ray time (58.2+/-23.1 min vs. 94.9+/-18.6 min,
      p<0.001), patient dose-area product (23,970+/-8,555 cGy.cm2 vs. 44,475+/-10,573
      cGy.cm2, p<0.001) and contrast consumption (177+/-33 ml vs. 271+/-70 ml, p<0.001)
      were significantly reduced in the DC group. One-year major adverse cardiac event
      free survival did not differ between the two groups (89.4% vs. 84.9%, p=0.36).
      CONCLUSIONS: The use of a 5-in-6 DC technique, especially as a bailout strategy,
      is a more effective back-up support of the guiding system, subsequently
      facilitating the success of transradial PCI for complex coronary lesions, than a
      conventional buddy-wire or balloon-anchoring approach.

PMID- 23171805
TI  - Comparison of intravascular ultrasound versus angiography-guided drug-eluting
      stent implantation: a meta-analysis of one randomised trial and ten observational
      studies involving 19,619 patients.
AB  - AIMS: The impact of intravascular ultrasound (IVUS) guided coronary drug-eluting
      stent (DES) implantation on clinical outcomes remains controversial. A meta
      analysis of the currently available clinical trials investigating IVUS-guided DES
      implantation was undertaken. METHODS AND RESULTS: We searched Medline, the
      Cochrane Library and other internet sources, without language or date
      restrictions, for published articles comparing clinical outcomes between IVUS
      guided and angiography-guided DES implantation. Clinical studies with both
      adjusted and unadjusted data were included. Eleven studies were identified (one
      randomised controlled trial and 10 registries) and included in the meta-analysis
      with a weighted follow-up time of 20.7+/-11.5 months. Compared with angiography
      guidance, IVUS-guided DES implantation was associated with a reduced incidence of
      death (hazard ratio [HR]: 0.59, 95% confidence interval [CI]: 0.48-0.73,
      p<0.001), major adverse cardiac events (HR: 0.87, 95% CI: 0.78-0.96, p=0.008) and
      stent thrombosis (HR: 0.58, 95% CI: 0.44-0.77, p<0.001). The incidence of
      myocardial infarction (HR: 0.82, 95% CI: 0.63-1.06, p=0.126), target lesion (HR:
      0.90, 95% CI: 0.73-1.11, p=0.316) and target vessel (HR: 0.90, 95% CI: 0.77-1.05,
      p=0.195) revascularisation was comparable between the angiography and IVUS-guided
      arms. A repeat meta-analysis of propensity-matched studies only (six studies,
      n=5,300) yielded broadly similar results in terms of clinical outcomes.
      CONCLUSIONS: IVUS-guided coronary DES implantation is associated with a
      significant reduction in death, MACE and stent thrombosis compared to angiography
      guidance. Appropriately powered randomised trials are necessary to confirm the
      findings from this meta-analysis.

PMID- 23171806
TI  - How should I treat a massive thrombus embolisation in the left coronary artery
      during chronic total occlusion revascularisation?
AB  - BACKGROUND: A 53-year-old man symptomatic for unstable angina, underwent PCI for
      a severe stenosis of the first obtuse marginal and a CTO of the left circumflex
      arteries. INVESTIGATIONS: Physical examination, myocardial necrosis markers, ECG,
      transthoracic echocardiography, exercise ECG test, bilateral coronary
      angiography, cardiac magnetic resonance. DIAGNOSIS: During PCI, antegrade
      contrast injection displaced a large clot from the guiding catheter into the left
      coronary artery causing massive thrombosis. The patient became haemodynamically
      unstable. The pressure wave from the guiding catheter was damped. MANAGEMENT:
      Intravenous UFH and abciximab followed by aspiration from the guiding catheter,
      and then through an aspiration catheter, until clear blood came out and pressure
      wave was normalised. Subsequent left coronary angiography showed no residual
      thrombi with TIMI-3 flow. Afterwards, a CMR scan showed no myocardial damage.

PMID- 23171807
TI  - Radial stent deformation in saphenous vein graft.

PMID- 23171808
TI  - The development and application of new crystallization method for tobacco mosaic
      virus coat protein.
AB  - BACKGROUND: Although tobacco mosaic virus (TMV) coat protein (CP) has been
      isolated from virus particles and its crystals have grown in ammonium sulfate
      buffers for many years, to date, no one has reported on the crystallization of
      recombinant TMV-CP connecting peptides expressed in E. coli. METHODS: In the
      present papers genetically engineered TMV-CP was expressed, into which
      hexahistidine (His) tags or glutathione-S-transferase (GST) tags were
      incorporated. Considering that GST-tags are long peptides and His-tags are short
      peptides, an attempt was made to grow crystals of TMV-CP cleaved GST-tags (WT-TMV
      CP32) and TMV-CP incorporated His-tags (WT-His-TMV-CP12) simultaneously in
      ammonium sulfate buffers and commercial crystallization reagents. It was found
      that the 20S disk form of WT-TMV-CP32 and WT-His-TMV-CP12 did not form high
      resolution crystals by using various crystallization buffers and commercial
      crystallization reagents. Subsequently, a new experimental method was adopted in
      which a range of truncated TMV-CP was constructed by removing several amino acids
      from the N- or the C-terminal, and high resolution crystals were grown in
      ammonium sulfate buffers and commercial crystallization reagents. RESULTS: The
      new crystallization method was developed and 3.0 A resolution macromolecular
      crystal was thereby obtained by removing four amino acids at the C-terminal of
      His-TMV-CP and connecting six His-tags at the N-terminal of His-TMV-CP (TR-His
      TMV-CP19). The Four-layer aggregate disk structure of TR-His-TMV-CP19 was solved.
      This phenomenon showed that peptides at the C-terminus hindered the growth of
      high resolution crystals and the peptides interactions at the N-terminus were
      attributed to the quality of TMV-CP crystals. CONCLUSION: A 3.0 A resolution
      macromolecular crystal of TR-His-TMV-CP19 was obtained and the corresponding
      structure was solved by removing four amino acids at the C-terminus of TMV-CP and
      connecting His-tags at the N-terminus of TMV-CP. It indicated that short peptides
      influenced the resolution of TMV-CP crystals.

PMID- 23171810
TI  - Incremental parameter estimation of kinetic metabolic network models.
AB  - BACKGROUND: An efficient and reliable parameter estimation method is essential
      for the creation of biological models using ordinary differential equation (ODE).
      Most of the existing estimation methods involve finding the global minimum of
      data fitting residuals over the entire parameter space simultaneously.
      Unfortunately, the associated computational requirement often becomes
      prohibitively high due to the large number of parameters and the lack of complete
      parameter identifiability (i.e. not all parameters can be uniquely identified).
      RESULTS: In this work, an incremental approach was applied to the parameter
      estimation of ODE models from concentration time profiles. Particularly, the
      method was developed to address a commonly encountered circumstance in the
      modeling of metabolic networks, where the number of metabolic fluxes (reaction
      rates) exceeds that of metabolites (chemical species). Here, the minimization of
      model residuals was performed over a subset of the parameter space that is
      associated with the degrees of freedom in the dynamic flux estimation from the
      concentration time-slopes. The efficacy of this method was demonstrated using two
      generalized mass action (GMA) models, where the method significantly outperformed
      single-step estimations. In addition, an extension of the estimation method to
      handle missing data is also presented. CONCLUSIONS: The proposed incremental
      estimation method is able to tackle the issue on the lack of complete parameter
      identifiability and to significantly reduce the computational efforts in
      estimating model parameters, which will facilitate kinetic modeling of genome
      scale cellular metabolism in the future.

PMID- 23171809
TI  - Attributes of Oct4 in stem cell biology: perspectives on cancer stem cells of the
      ovary.
AB  - Epithelial ovarian cancer (EOC) remains the most lethal of all the
      gynaecological malignancies with drug resistance and recurrence remaining the
      major therapeutic barrier in the management of the disease. Although several
      studies have been undertaken to understand the mechanisms responsible for
      chemoresistance and subsequent recurrence in EOC, the exact mechanisms associated
      with chemoresistance/recurrence continue to remain elusive. Recent studies have
      shown that the parallel characteristics commonly seen between embryonic stem
      cells (ESCs) and induced pluripotent stem cells (iPSC) are also shared by a
      relatively rare population of cells within tumors that display stem cell-like
      features. These cells, termed 'cancer initiating cells' or 'cancer stem cells
      (CSCs)' have been shown not only to display increased self renewal and
      pluripotent abilities as seen in ESCs and iPSCs, but are also highly tumorigenic
      in in vivo mouse models. Additionally, these CSCs have been implicated in tumor
      recurrence and chemoresistance, and when isolated have consistently shown to
      express the master pluripotency and embryonic stem cell regulating gene Oct4.
      This article reviews the involvement of Oct4 in cancer progression and
      chemoresistance, with emphasis on ovarian cancer. Overall, we highlight why
      ovarian cancer patients, who initially respond to conventional chemotherapy
      subsequently relapse with recurrent chemoresistant disease that is essentially
      incurable.

PMID- 23171811
TI  - Variant of ETV6/ABL1 gene is associated with leukemia phenotype.
AB  - The ETV6/ABL1 fusion transcript is thought to be a very rare aberration in
      hematopoietic malignancies. We describe two new cases of acute leukemia with the
      ETV6/ABL1 fusion, acute myeloid leukemia with eosinophilia (case 1) and B acute
      lymphoblastic leukemia (ALL) (case 2), screened by multiplex RT-PCR. The
      ETV6/ABL1 fusion was also confirmed by fluorescence in situ hybridization using a
      mixture of BCR/ABL1 and ETV6/RUNX1 probes. A thorough review of all published
      cases showed that all 7 reported ALL patients possess the type A ETV6/ABL1 fusion
      transcript, composed of the first 4 exons of ETV6 fused to the second exon of
      ABL1. The presence of the type A fusion transcript strongly implies ALL
      manifestation in ETV6/ABL1-positive hematologic malignancies as minor BCR
      breakpoint in BCR/ABL1-positive ALL.

PMID- 23171812
TI  - Variant rabbit hemorrhagic disease virus in young rabbits, Spain.
AB  - Outbreaks of rabbit hemorrhagic disease have occurred recently in young rabbits
      on farms on the Iberian Peninsula where rabbits were previously vaccinated.
      Investigation identified a rabbit hemorrhagic disease virus variant genetically
      related to apathogenic rabbit caliciviruses. Improved antivirus strategies are
      needed to slow the spread of this pathogen.

PMID- 23171813
TI  - Vitex rotundifolia L. prevented airway eosinophilic inflammation and airway
      remodeling in an ovalbumin-induced asthma mouse model.
AB  - Vitex rotundifolia L. (VR) as long been used in China and Korea in traditional
      medicine. This study was conducted to evaluate the ability of Vitex rotundifolia
      L. to prevent airway inflammation and remodeling in an ovalbumin (OVA)-induced
      murine asthma model. The total cell number and number of inflammatory cells in
      the bronchoalveolar lavage (BAL) fluid were counted. The levels of cytokines in
      the BAL fluid and serum IgE levels were measured using an ELISA. For histological
      analysis, hematoxylin and eosin staining, periodic acid-Schiff staining and
      immunohistochemistry were evaluated. The release of total cells into the BAL
      fluid was significantly inhibited in OVA-induced asthmatic mice treated with VR
      extract. In addition, eosinophilia and lymphocytosis were reduced significantly
      in mice that received VR extract. Furthermore, levels of the T(h)2 cytokines IL-4
      and IL-5 and pro-inflammatory cytokine TNF-alpha in the BAL fluid and total IgE
      in serum were markedly suppressed by VR extract. OVA-specific IgE in the serum
      and IL-13 in the BAL fluid were decreased, but not significantly. The allergic
      effects of VR extract were accompanied by a reduction in airway
      hyperresponsiveness. Additionally, morphologic findings demonstrated that VR
      extract substantially inhibited OVA-induced eosinophilia, goblet cell hyperplasia
      and smooth muscle mass production. This finding suggests that VR extract may have
      pharmacological effects that would be useful for the treatment of asthma via the
      inhibition of the T(h)2 response and airway remodeling.

PMID- 23171814
TI  - African swine fever virus, Tanzania, 2010-2012.

PMID- 23171815
TI  - Does exercise improve self-reported sleep quality in non-remitted major
      depressive disorder?
AB  - BACKGROUND: Sleep disturbances are persistent residual symptoms following
      remission of major depressive disorder (MDD) and are associated with an increased
      risk of MDD recurrence. The purpose of the current study was to examine the
      effect of exercise augmentation on self-reported sleep quality in participants
      with non-remitted MDD. Method Participants were randomized to receive selective
      serotonin reuptake inhibitor (SSRI) augmentation with one of two doses of
      exercise: 16 kilocalories per kilogram of body weight per week (KKW) or 4 KKW for
      12 weeks. Depressive symptoms were assessed using the clinician-rated Inventory
      of Depressive Symptomatology (IDS-C). The four sleep-related items on the IDS-C
      (Sleep Onset Insomnia, Mid-Nocturnal Insomnia, Early Morning Insomnia, and
      Hypersomnia) were used to assess self-reported sleep quality. RESULTS:
      Significant decreases in total insomnia (p < 0.0001) were observed, along with
      decreases in sleep onset, mid-nocturnal and early-morning insomnia (p's <0.002).
      Hypersomnia did not change significantly (p = 0.38). Changes in total, mid
      nocturnal and early-morning insomnia were independent of changes in depressive
      symptoms. Higher baseline hypersomnia predicted a greater decrease in depression
      severity following exercise treatment (p = 0.0057). No significant moderating
      effect of any baseline sleep on change in depression severity was observed. There
      were no significant differences between exercise treatment groups on total
      insomnia or any individual sleep item. CONCLUSIONS: Exercise augmentation
      resulted in improvements in self-reported sleep quality in patients with non
      remitted MDD. Given the prevalence of insomnia as a residual symptom following
      MDD treatment and the associated risk of MDD recurrence, exercise augmentation
      may have an important role in the treatment of MDD.

PMID- 23171816
TI  - Alzheimer's disease and retinal neurodegeneration share a consistent stress
      response of the neurovascular unit.
AB  - BACKGROUND: The pathogenesis of Alzheimer's disease (AD) is characterized by
      neuronal injury, activation of microglia and astrocytes, deposition of amyloid
      beta and secondary vessel degeneration. In the polycystic kidney disease (PKD)
      rat model, we observed neuronal injury, microglial activation and vasoregression.
      We speculated that this neuroretinal degeneration shares important pathogenetic
      steps with AD. Therefore, we determined the activation of astrocytes and the
      accumulation of amyloid-beta in PKD retinae. METHODS: Immunohistochemistry of PKD
      retinae for vimentin, carboxymethyllysin, beta-Amyloid 1-42, High-Mobility-Group-
      Protein B1 and amyloid protein precursor was performed. RESULTS: Adjunct to
      astrocyte activation, accumulation of beta-Amyloid 1-42 and High-Mobility-Group
      Protein B1 in astrocytes and around vessels of the superficial network was found
      in PKD retinae prior to the onset of vasoregression. Amyloid precursor protein
      was localized adjacent to the outer segment of photoreceptors in PKD and control
      rats. The parallel appearance of AD-related peptides indicates an alarmine based
      response to photoreceptor degeneration and secondary vasoregression. CONCLUSION:
      The model has broad overlap with AD and may be suitable to study beneficial
      pharmacological concepts.

PMID- 23171817
TI  - Preface.

PMID- 23171818
TI  - Do psychopaths feel empathy?

PMID- 23171819
TI  - Aquaporin-2 levels in vitro and in vivo are regulated by VACM-1, a cul 5 gene.
AB  - BACKGROUND: In the renal collecting duct, vasopressin regulates water
      permeability by a process that involves stimulation of adenylyl cyclase activity,
      cAMP production and subsequent translocation of water channel aquaporin-2 (AQP2)
      into the apical plasma membrane. We have previously shown that in cos 1 cells in
      vitro, both adenylyl cyclase activity and cAMP production can be regulated by
      VACM-1, a cul 5 gene that forms complexes involved in protein ubiquitination and
      subsequent degradation. METHODS: To extend these observations further, the
      effects of changes in hydration state on the expression of VACM-1 at the mRNA and
      the protein level were examined in rats deprived of water (WD) for 24 hrs.
      RESULTS: In the kidney of WD rats Western blot analyses of kidney tissue showed
      that the decrease in VACM-1 protein concentration was correlated with the
      increase in the AQP2 protein level. The immunostaining data suggested that VACM
      1/cul5 may be decreased in renal collecting duct but increases in the vasculature
      of the inner medullary region in response to WD. To determine the possible
      consequences of the WD dependent decrease in VACM-1/cul5, we next examined the
      effects of VACM-1 expression on AQP2 protein in vitro. Immunocytochemistry and
      Western blot analyses data indicate that VACM-1/cul5 expression in MDCK line
      stably expressing AQP2 gene and in cos 1 cells co-transfected with the AQP2 and
      VACM-1/cul5 cDNAs decreased AQP2 protein concentration when compared to the
      vector transfected control groups. CONCLUSION: In summary, our data demonstrate
      that VACM-1 is involved in the regulation of AQP2 protein concentration and may
      play a role in regulating water balance.

PMID- 23171820
TI  - Exploring perceptions of psychological services in a children's hospice in the
      United Kingdom.
AB  - BACKGROUND: The provision of emotional and psychological support for all family
      members who need it is an essential element of holistic palliative care. Within
      East Anglia's Children's Hospice, teams of professionally trained and experienced
      workers offer psychosocial support to all family members at all times during the
      child's and family's journey. However, the effectiveness and appropriateness of
      current psychosocial provision is unclear, as is the requirement for any
      additional psychological services. OBJECTIVE: The purpose of this study was to
      elicit perceptions about current psychological support within the hospice from a
      group of stakeholders (parents, hospice staff, and external professionals).
      METHOD: Forty-five parents participated in family focus groups, telephone
      interviews, individual interviews in their home, or a web-based survey. Ninety
      five hospice staff (including nurses, carers, play specialists, therapists, and
      family support practitioners) and 28 external staff (including physicians,
      nurses, and commissioning managers) were seen using a mixture of focus group and
      individual meetings. Focus groups and meetings were held at the hospice building
      or at an external venue. Interviews were recorded and transcribed verbatim and
      analyzed using thematic coding. RESULTS: Two main themes addressing perceptions
      of current psychological provision emerged: "understanding psychological support"
      and "unmet psychological need." Subthemes linked to support included choice,
      staff roles and labels, communication, and flexibility, whereas the themes within
      unmet need had a stronger focus on people and problems. SIGNIFICANCE OF RESULTS:
      Understanding different user perspectives is an important first step in enhancing
      current psychological provision; operationalizing the findings will be
      challenging.

PMID- 23171821
TI  - Fifth European Antibiotic Awareness Day on 18 November: joining forces to reduce
      antibiotic resistance.

PMID- 23171823
TI  - Haemophilus influenzae serotype B (Hib) seroprevalence in England and Wales in
      2009.
AB  - A national seroprevalence study was performed to determine the prevalence of
      Haemophilus influenzae type b (Hib) antibodies in England and Wales in 2009, when
      Hib disease incidence was the lowest ever recorded. A total of 2,693 anonymised
      residual sera from routine diagnostic testing submitted by participating National
      Health Service hospital laboratories were tested for Hib anti-polyribosyl-ribitol
      phosphate (PRP) IgG antibodies using a fluorescent bead assay. Median anti-PRP
      IgG concentrations were highest in toddlers aged 1-4 years (2.65 MUg/ml),
      followed by children aged 5-9 years (1.95 MUg/ml). Antibody concentrations were
      significantly lower after this age, but were still significantly higher among 10
      19 year-olds (0.54 MUg/ml) compared with adults aged >20 years (0.16 MUg/ ml;
      p<0.0001). Half of the adults (51%) did not have Hib antibody concentrations
      >=0.15 MUg/ml, the level considered to confer short-term protection. Thus, the
      current excellent Hib control appears to be the result of high anti-PRP antibody
      concentrations in children aged up to 10 years, achieved through the various
      childhood vaccination campaigns offering booster immunisation. The lack of
      seroprotection in adults emphasises the importance of maintaining control of the
      disease and, most probably carriage, in children, therefore raising the question
      as to whether long-term routine boosting of either pre-school children or
      adolescents may be required.

PMID- 23171822
TI  - The European Centre for Disease Prevention and Control (ECDC) pilot point
      prevalence survey of healthcare-associated infections and antimicrobial use.
AB  - A standardised methodology for a combined point prevalence survey (PPS) on
      healthcare-associated infections (HAIs) and antimicrobial use in European acute
      care hospitals developed by the European Centre for Disease Prevention and
      Control was piloted across Europe. Variables were collected at national, hospital
      and patient level in 66 hospitals from 23 countries. A patient-based and a unit
      based protocol were available. Feasibility was assessed via national and hospital
      questionnaires. Of 19,888 surveyed patients, 7.1% had an HAI and 34.6% were
      receiving at least one antimicrobial agent. Prevalence results were highest in
      intensive care units, with 28.1% patients with HAI, and 61.4% patients with
      antimicrobial use. Pneumonia and other lower respiratory tract infections (2.0%
      of patients; 95% confidence interval (CI): 1.8-2.2%) represented the most common
      type (25.7%) of HAI. Surgical prophylaxis was the indication for 17.3% of used
      antimicrobials and exceeded one day in 60.7% of cases. Risk factors in the
      patient-based protocol were provided for 98% or more of the included patients and
      all were independently associated with both presence of HAI and receiving an
      antimicrobial agent. The patient-based protocol required more work than the unit
      based protocol, but allowed collecting detailed data and analysis of risk factors
      for HAI and antimicrobial use.

PMID- 23171824
TI  - Two geographically separated food-borne outbreaks in Sweden linked by an unusual
      Cryptosporidium parvum subtype, October 2010.
AB  - The number of sporadic cases of Cryptosporidium identified in the Stockholm
      county area increased above the expected limit during October 2010. Additionally,
      two food-borne outbreaks of cryptosporidiosis occurred in two other Swedish
      cities: Umea (4 October) and Orebro (9 October). The outbreak investigations did
      not reveal any responsible food item, however fresh herbs were suspected. Thirty
      stool samples, originating from all three events, tested positive for
      Cryptosporidium oocysts. Polymerase chain reaction (PCR) and subsequent
      restriction fragment length polymorphism (RFLP) revealed that 27 individuals were
      infected with C. parvum, two with C. hominis, and one with C. felis. Using
      sequence analysis of the GP60 glycoprotein gene, a polymorphic marker with high
      intra-species diversity, we identified the same C. parvum subtype IIdA24G1 in
      samples from both the Umea outbreak and the Stockholm area cases, thus indicating
      a possible outbreak in the Stockholm area and establishing a link between these
      two events. C. parvum IIdA24G1 has not previously been described in connection
      with a food-borne outbreak. For the outbreak in Orebro, another subtype was
      identified: C. parvum IIdA20G1e. These findings demonstrate that subtyping C.
      parvum isolates using GP60 gene amplification can be used to link cases in an
      outbreak investigation and we recommend its use in future similar events.

PMID- 23171825
TI  - EMCDDA publishes 2012 report on the state of the drugs problem in Europe.

PMID- 23171827
TI  - Young men, mental health, and technology: implications for service design and
      delivery in the digital age.
AB  - BACKGROUND: Young men are particularly vulnerable to suicide, drug, and alcohol
      problems and yet fail to seek appropriate help. An alternative or adjunct to face
      to-face services has emerged with widespread uptake of the Internet and related
      communication technologies, yet very little evidence exists that examines the
      capacity of the Internet to engage young men and promote help seeking. OBJECTIVE:
      To explore young people's attitudes and behaviors in relation to mental health
      and technology use. The aim was to identify key gender differences to inform the
      development of online mental health interventions for young men. METHODS: A cross
      sectional online survey of 1038 young people (aged 16 to 24 years) was used.
      RESULTS: Young men are more likely than young women to play computer games,
      access online video/music content, and visit online forums. More than half of
      young men and women reported that they sought help for a problem online, and the
      majority were satisfied with the help they received. Significant gender
      differences were identified in relation to how young people would respond to a
      friend in need, with young men being less likely than young women to confront the
      issue directly. CONCLUSIONS: Online interventions for young men need to be action
      oriented, informed by young men's views and everyday technology practices, and
      leverage the important role that peers play in the help-seeking process.

PMID- 23171828
TI  - DPP-4 inhibition on top of angiotensin receptor blockade offers a new therapeutic
      approach for diabetic nephropathy.
AB  - BACKGROUND: The need for an improved treatment for diabetic nephropathy is
      greatest in patients who do not adequately respond to angiotensin II receptor
      blockers (ARBs). This study investigated the effect of the novel dipeptidyl
      peptidase-4 inhibitor linagliptin alone and in combination with the ARB
      telmisartan on the progression of diabetic nephropathy in diabetic endothelial
      nitric oxide synthase (eNOS) knockout mice. METHODS: Sixty male eNOS knockout
      C57BL/6J mice were divided into four groups after receiving intraperitoneal
      highdose streptozotocin: telmisartan (1 mg/kg), linagliptin (3 mg/kg),
      linagliptin + telmisartan (3 mg/kg + 1 mg/kg) and vehicle. Fourteen mice were
      used as non-diabetic controls. RESULTS: After 12 weeks, urine and blood were
      obtained and blood pressure measured. Glucose concentrations were increased and
      similar in all diabetic groups. Telmisartan alone reduced systolic blood pressure
      by 5.9 mmHg versus diabetic controls (111.2 +/- 2.3 mmHg vs 117.1 +/- 2.2 mmHg;
      mean +/- SEM; P=0.071). Combined treatment significantly reduced albuminuria
      compared with diabetic controls (71.7 +/- 15.3 ug/24 h vs. 170.8 +/- 34.2 ug/24
      h; P=0.017), whereas the effects of single treatment with either telmisartan
      (97.8 +/- 26.4 ug/24 h) or linagliptin (120.8 +/- 37.7 ug/24 h) were not
      statistically significant. DPP-4 inhibition, alone and in combination, led to
      significantly lower plasma osteopontin levels compared with telmisartan alone.
      Histological analysis revealed reduced glomerulosclerosis after Linagliptin alone
      and in combination with telmisartan in comparison to non treated diabetic animals
      (p<0.01 and p<0.05). Kidney malonaldehyde immune-reactivity, a marker of
      oxidative stress, was significantly lower in animals treated with linagliptin.
      CONCLUSIONS: DPP-4 inhibition on top of ARB treatment significantly reduced
      urinary albumin excretion and oxidative stress in diabetic eNOS knockout mice.
      Linagliptin on top of an angiotensin II receptor blocker may offer a new
      therapeutic approach for patients with diabetic nephropathy.

PMID- 23171830
TI  - Controlling highly pathogenic avian influenza, Bangladesh.

PMID- 23171829
TI  - Biological characteristics of the rtA181T/sW172* mutant strain of Hepatitis B
      virus in animal model.
AB  - BACKGROUND: The effects of Hepatitis B virus (HBV) rtA181T/sW172* mutation on
      viral replication and pathogenicity was concerned recently. This study aimed to
      investigate the biological characteristics of rtA181T/sW172* mutant strain of HBV
      in animal model. METHODS: The rtA181T/sW172* mutant plasmid was constructed using
      the pHBV4.1 (wild type HBV) as a template. The wild and mutant HBV replication
      mouse models were established utilizing a hydrodynamic technique. The titers of
      hepatitis B surface antigen (HBsAg), hepatitis B e antigen, and HBV DNA in serum,
      and the levels of HBsAg, hepatitis B core antigen(HBcAg), HBV DNA replication
      intermediates (HBV DNA RI) and HBV RNA in liver were measured after 1, 3, 5, 7,
      10, 12 and 15 days of plasmid injection. RESULTS: In wild-type HBV replication
      mouse model, serum HBsAg was high on day 1, 3, and 5, but became lower since day
      7; while in mutant HBV mouse model, serum HBsAg was always at very low level. In
      liver tissues, HBV DNA RI of wild type HBV was detected on day 1 after
      transfection. The level subsequently peaked on day 3, gradually declined after
      day 5, and was almost undetectable on day 10. However, the HBV DNA RI levels of
      the mutant strain were always higher and lasted longer until day 15.
      Consistently, the expression levels of HBsAg and HBcAg in liver of the mutant
      group were significantly increased. CONCLUSIONS: In the case of the HBV
      rtA181T/sW172* mutation, the secretion of serum HBsAg was impaired, whereas HBV
      DNA replication and HBsAg/HBcAg expression were increased in liver. These results
      suggest that the mutation can impair HBsAg secretion, and may cause the
      accumulation of viral core particles in liver.

PMID- 23171831
TI  - Glycemic variability is complex--is glucose complexity variable?
AB  - Observational studies show an independent association between increased glycemic
      variability and higher mortality in critically ill patients. Minimization of
      glycemic variability is therefore suggested as a new target of glycemic control,
      which may require very frequent or almost continuous monitoring of glucose
      levels. Brunner and colleagues show the use of real-time subcutaneous continuous
      glucose monitoring does not decrease glycemic variability. Continuous glucose
      monitoring, however, may reveal changes in glucose complexity, which may be of
      interest since both increased and decreased glucose complexity is associated with
      higher mortality in the critically ill. 

PMID- 23171832
TI  - Depressed mood, glycaemic control and functional capacity in overweight/obese men
      with and without type 2 diabetes.
AB  - OBJECTIVE: To determine whether there were differences in depressed mood between
      overweight/obese men with and without type 2 diabetes (T2DM) and to examine any
      associations between depressed mood, physical functioning, and glycaemic control
      in overweight/obese men with and without T2DM. METHODS: Fifty seven
      overweight/obese men with (n = 19, age = 54.2 +/- 7.4 yrs, BMI = 32.3 +/- 6.7
      kg?m-2) and without T2DM (n = 38, age = 51.1 +/- 6.8 yrs, BMI = 29.9 +/- 4.5kg?m
      2, p > 0.05 between groups) participated. The men completed measures of depressed
      mood and health-related quality of life (HRQL) and underwent the following
      assessments: fasting blood lipids and glucose, HbA1c, anthropometric
      measurements, VO2peak, muscle strength, and physical function. RESULTS: Compared
      to men without T2DM, men with T2DM had higher depressed mood (p = 0.05, eta2 =
      0.07), as well as lower perceived general health (p < .01, eta2 = 0.24) and
      social functioning (p = .01, eta2 = 0.10). Men with T2DM also had lower VO2peak
      (21.8 +/- 5.3 versus 25.8 +/- 5.4 ml?kg-1?min-1, p < .01, eta2 = 0.11) and muscle
      strength (3.3 +/- 0.8 versus 3.7 +/- 0.7 kg?kg-1, p = 0.08, eta2 = 0.06), as well
      as being slower to complete physical performance tasks (27.2 +/- 5.2 versus 24.2
      +/- 2.8 sec, p < 0.01, eta2 = 0.13). In those with T2DM, depressed mood was
      highly correlated with most HRQL subscales. For the combined cohort, depressed
      mood was correlated with fasting glucose (r = 0.31, p = 0.012) but not the
      functional measures. CONCLUSIONS: Men with T2DM have higher levels of depressed
      mood compared to men without T2DM. Glycaemic control, but not functional
      capacities, is associated with depressed mood in the study cohort.

PMID- 23171833
TI  - A 4-year prospective observational follow-up study of course and predictors of
      course in body dysmorphic disorder.
AB  - BACKGROUND: This report prospectively examines the 4-year course, and predictors
      of course, of body dysmorphic disorder (BDD), a common and often severe disorder.
      No prior studies have prospectively examined the course of BDD in individuals
      ascertained for BDD. Method The Longitudinal Interval Follow-Up Evaluation (LIFE)
      assessed weekly BDD symptoms and treatment received over 4 years for 166 broadly
      ascertained adults and adolescents with current BDD at intake. Kaplan-Meier life
      tables were constructed for time to remission and relapse. Full remission was
      defined as minimal or no BDD symptoms, and partial remission as less than full
      DSM-IV criteria, for at least 8 consecutive weeks. Full relapse and partial
      relapse were defined as meeting full BDD criteria for at least 2 consecutive
      weeks after attaining full or partial remission respectively. Cox proportional
      hazards regression examined predictors of remission and relapse. RESULTS: Over 4
      years, the cumulative probability was 0.20 for full remission and 0.55 for full
      or partial remission from BDD. A lower likelihood of full or partial remission
      was predicted by more severe BDD symptoms at intake, longer lifetime duration of
      BDD, and being an adult. Among partially or fully remitted subjects, the
      cumulative probability was 0.42 for subsequent full relapse and 0.63 for
      subsequent full or partial relapse. More severe BDD at intake and earlier age at
      BDD onset predicted full or partial relapse. Eighty-eight percent of subjects
      received mental health treatment during the follow-up period. CONCLUSIONS: In
      this observational study, BDD tended to be chronic. Several intake variables
      predicted greater chronicity of BDD.

PMID- 23171834
TI  - A case of 8p11 myeloproliferative syndrome with BCR-FGFR1 gene fusion presenting
      with trilineage acute leukemia/lymphoma, successfully treated by cord blood
      transplantation.
AB  - The 8p11 myeloproliferative syndrome is a rare neoplasm associated with
      chromosomal translocations involving the fibroblast growth factor receptor 1
      (FGFR1) gene located at chromosome 8p11-12. FGFR1 encodes a transmembrane
      receptor tyrosine kinase. The resultant fusion proteins are constitutively active
      tyrosine kinases that drive the proliferation of hematopoietic cells, whose
      uncontrolled growth can present as a myeloproliferative neoplasm. We report here
      the case of a 50-year-old man harboring the t(8;22)(p12;q11) chromosomal
      translocation in cells from both bone marrow and lymph nodes. He presented with
      acute leukemia and lymphoma with trilineage features. A novel mRNA in-frame
      fusion between exon 4 of the breakpoint cluster region (BCR) gene at chromosome
      22q11 and exon 9 of FGFR1 gene on chromosome 8p11-12 was identified by reverse
      transcription polymerase chain reaction analysis and was confirmed by DNA
      sequencing. Because the patient was refractory to chemotherapy, cord blood
      transplantation was performed in progressive disease. It resulted in a successful
      outcome in which cytogenetic complete remission has been maintained for 2 years
      till date.

PMID- 23171835
TI  - Reservoir competence of vertebrate hosts for Anaplasma phagocytophilum.
AB  - Fourteen vertebrate species (10 mammals and 4 birds) were assessed for their
      ability to transmit Anaplasma phagocytophilum, the bacterium that causes human
      granulocytic anaplasmosis, to uninfected feeding ixodid ticks. Small mammals were
      most likely to infect ticks but all species assessed were capable of transmitting
      the bacterium, in contrast to previous findings.

PMID- 23171836
TI  - A(3) adenosine receptor mediates apoptosis in 5637 human bladder cancer cells by
      G(q) protein/PKC-dependent AIF upregulation.
AB  - BACKGROUND/AIMS: A(3) adenosine receptor mediates apoptosis in a variety of
      cancer cells via diverse signaling pathways. The present study was conducted to
      assess A(3) adenosine receptor-mediated apoptosis in human bladder cancer cell
      lines and to understand the underlying mechanism. METHODS: Human bladder cancer
      cell lines such as 253J, 5637, KK-47, TCCSUP, T24, and UMUC-3 cells were
      cultured. The siRNA to silence the A(3) adenosine receptor-targeted gene was
      constructed and transfected into cells. MTT assay, TUNEL staining, Western
      blotting, and real-time RT-PCR were carried out. RESULTS: For all the
      investigated cell types adenosine induced apoptosis in a concentration (0.01-10
      mM)- and treatment time (24-48 h)-dependent manner. Adenosine-induced 5637 cell
      death was significantly inhibited by the A(3) adenosine receptor inhibitor
      MRS1191 or knocking-down A(3) adenosine receptor, and the A(3) adenosine receptor
      agonist 2-Cl-IB-MECA mimicked the adenosine effect. The adenosine effect was
      prevented by GF109203X, an inhibitor of protein kinase C (PKC), but it was not
      affected by forskolin, an activator of adenylate cyclase. Adenosine-induced 5637
      cell death, alternatively, was not inhibited by the pan-caspase inhibitor Z-VAD.
      Adenosine upregulated expression of apoptosis-inducing factor (AIF), that is
      suppressed by knocking-down A(3) adenosine receptor, and accumulated AIF in the
      nucleus. CONCLUSION: The results of the present study show that adenosine induces
      5637 cell apoptosis by upregulating AIF expression via an A(3) adenosine receptor
      mediated G(q) protein/PKC pathway.

PMID- 23171837
TI  - Efficacy of chemotherapy for advanced non-small cell lung cancer with idiopathic
      pulmonary fibrosis.
AB  - BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is the most common type of
      idiopathic interstitial pneumonia and is associated with an independent increased
      risk of lung carcinogenesis. The benefit of chemotherapy for lung cancer in cases
      of IPF remains unknown. OBJECTIVES: This study was conducted to elucidate the
      efficacy of chemotherapy for advanced non-small cell lung cancer (NSCLC) in
      patients with IPF. METHODS: Advanced (i.e. stage IIIB and IV) NSCLC patients with
      IPF who received systemic chemotherapy were studied. Response rate, toxicity,
      overall survival and progression-free survival were investigated. RESULTS:
      Between January 2000 and December 2009, 21 patients were enrolled in this study
      and treated with chemotherapy. The overall response rate with the 1st regimen was
      42.9%. The median overall survival was 11.4 months, the 1-year survival rate was
      28.6% and the median PFS was 5.4 months. CONCLUSIONS: This study showed that
      advanced NSCLC patients with IPF may benefit from chemotherapy; well-controlled
      studies are still needed to clarify the efficacy.

PMID- 23171838
TI  - Increasing physical activity with mobile devices: a meta-analysis.
AB  - BACKGROUND: Regular physical activity has established physical and mental health
      benefits; however, merely one quarter of the U.S. adult population meets national
      physical activity recommendations. In an effort to engage individuals who do not
      meet these guidelines, researchers have utilized popular emerging technologies,
      including mobile devices (ie, personal digital assistants [PDAs], mobile phones).
      This study is the first to synthesize current research focused on the use of
      mobile devices for increasing physical activity. OBJECTIVE: To conduct a meta
      analysis of research utilizing mobile devices to influence physical activity
      behavior. The aims of this review were to: (1) examine the efficacy of mobile
      devices in the physical activity setting, (2) explore and discuss implementation
      of device features across studies, and (3) make recommendations for future
      intervention development. METHODS: We searched electronic databases (PubMed,
      PsychINFO, SCOPUS) and identified publications through reference lists and
      requests to experts in the field of mobile health. Studies were included that
      provided original data and aimed to influence physical activity through
      dissemination or collection of intervention materials with a mobile device. Data
      were extracted to calculate effect sizes for individual studies, as were study
      descriptives. A random effects meta-analysis was conducted using the
      Comprehensive Meta-Analysis software suite. Study quality was assessed using the
      quality of execution portion of the Guide to Community Preventative Services data
      extraction form. RESULTS: Four studies were of "good" quality and seven of "fair"
      quality. In total, 1351 individuals participated in 11 unique studies from which
      18 effects were extracted and synthesized, yielding an overall weight mean effect
      size of g = 0.54 (95% CI = 0.17 to 0.91, P = .01). CONCLUSIONS: Research
      utilizing mobile devices is gaining in popularity, and this study suggests that
      this platform is an effective means for influencing physical activity behavior.
      Our focus must be on the best possible use of these tools to measure and
      understand behavior. Therefore, theoretically grounded behavior change
      interventions that recognize and act on the potential of smartphone technology
      could provide investigators with an effective tool for increasing physical
      activity.

PMID- 23171839
TI  - [Dysfunction of the blood-brain barrier during ischaemia: a therapeutic concern].
AB  - Since it was discovered and its brain-protective role characterized, the blood
      brain barrier (BBB), through the permeability-restricting action of the brain
      capillary endothelial cells, has been representing a hurdle for 95% of new
      medical compounds targeting the central nervous system. Recently, a BBB
      dysfunction is being found in an increasing number of pathologies such as brain
      ischaemic stroke, whose only therapy consists in a pharmacological thrombolysis
      limited to a small percentage of the admitted patients, because of the toxical
      effects of thrombolytics. And since the clinical failure of promising
      neuroprotectants, numerous studies of brain ischaemia were carried out, with
      physiopathological or pharmacological approaches refocused on the BBB, whose
      structural complexity is now expanded to perivascular cells, all forming a
      functional unit named the neurovascular unit (NVU). Nevertheless, in spite of the
      numerous molecular mechanisms identified, the process of BBB dysfunction in the
      ischaemia/reperfusion cascade remains insufficiently established to explain the
      pleiotropic action exerted by new pharmacological compounds, possibly protecting
      the entire NVU and representing potential treatments.

PMID- 23171840
TI  - [Recent advances in quantitative proteomics as a sensitive tool to quantify drug
      transporters and drug metabolizing enzymes at the human blood-brain barrier].
AB  - Since its discovery at the beginning of the 20th century, the blood-brain barrier
      (BBB) has been considered for a long time as a "physical barrier" able to limit
      brain distribution of highly molecular weight and/or polar compounds. This early
      concept of an anatomical barrier between the blood and the brain was supported by
      the finding of unique tight junctions between the brain endothelial cells so that
      they formed a continuous wall preventing the paracellular diffusion of solutes.
      In the middle of the 50's, BBB has been proposed as a "biochemical barrier" able
      to control the supply of brain to essential nutriments. More recently, BBB was
      evidenced as a key element in controlling effects of central nervous system
      drugs, since it plays a critical role in the uptake and efflux of drugs from the
      blood to the brain, or vice versa, hence affecting their concentrations and
      effects in the central nervous system (CNS). The BBB has therefore been more
      recently defined as a "pharmacological barrier" since the endothelial cells were
      found to contain a range of metabolizing enzymes and transporters that control
      the rate and extent of drugs reaching the brain parenchyma via transcellular
      pathway. The emergence of new quantitative proteomic approaches allows
      quantifying these transporters and enzymes at the BBB, opening the way to
      identify new drugs that may be targeted to the brain.

PMID- 23171841
TI  - [Nanoparticles for brain delivery of drugs or contrast agents. Application to
      Alzheimer's disease].
AB  - The treatment and the diagnosis of brain diseases like Alzheimer's are nowadays a
      real challenge. In fact the brain delivery of drugs or contrast agents is very
      difficult due to the low permeability of the blood brain barrier (BBB) which is
      situated in brain capillaries and assures a high protection of the brain against
      exogenous molecules or particles. Among the different strategies that have been
      proposed to increase the passage of drugs through the barrier, a non-invasive one
      is based on the use of colloidal carriers called nanoparticles. These nanometric
      objects chosen for their biocompatibility and biodegradation exhibit several
      fates and distributions according to their composition and structures, defining
      the three generations of nanoparticles described up to now. The application of
      nanoparticles to the treatment and diagnosis of Alzheimer's disease is actually
      investigated in a European project. Recent studies reveal that more than 3
      million people in Europe are afflicted with Alzheimer's disease. New treatments
      are urgently needed, as are diagnostic tests that can detect the disease earlier.
      The strategies developed in this project are based on the design of new carriers
      able to pass through the BBB and to interact with beta-amyloid peptide in order
      to (1) detect already formed brain plaques, aiming to diagnose the disease and
      (2) avoid peptide aggregation which is toxic for neurons, for the purpose of
      discovering a new therapeutic approach for Alzheimer's disease.

PMID- 23171843
TI  - [Transcriptional control of ciliogenesis in animal development].
AB  - Cilia and flagella are eukaryotic organelles with a conserved structure and
      function from unicellular organisms to human. In animals, different types of
      cilia can be found and cilia assembly during development is a highly dynamic
      process. Ciliary defects in human lead to a wide spectrum of diseases called
      ciliopathies. Understanding the molecular mechanisms that govern dynamic cilia
      assembly during development and in different tissues in metazoans is an important
      biological challenge. The FOXJ1 (Forkhead Box J1) and RFX (Regulatory Factor X)
      family of transcription factors have been shown to be important factors in
      ciliogenesis control. FOXJ1 proteins are required for motile ciliogenesis in
      vertebrates. By contrast, RFX proteins are essential to assemble both primary and
      motile cilia through the regulation of specific sets of genes such as those
      encoding intraflagellar transport components. Recently, new actors with more
      specific roles in cilia biogenesis and physiology have also been discovered. All
      these factors are subject to complex regulation, allowing for the dynamic and
      specific regulation of ciliogenesis in metazoans.

PMID- 23171842
TI  - [New protein vectors for physiological transfer of therapeutic agents to the
      central nervous system].
AB  - The central nervous system is a sanctuary protected by barriers, among which the
      blood-brain barrier (BBB). The BBB is formed by the specific nature of the
      endothelial cells of the brain capillaries, that allow brain access only to
      nutrients necessary for brain cell survival and function. These properties of the
      BBB result in the incapacity of therapeutic compounds, both small and large, to
      reach the brain at therapeutic concentrations. Various strategies are now being
      developed to enhance the amount and concentration of these compounds in the brain
      parenchyma. The development of new technologies such as peptide vectors will
      achieve the delivery of active agents in therapeutic concentration across the BBB
      to treat brain diseases such as cancer or neurodegenerative disorders. In this
      paper, design of new active peptides and the development of new protein, peptide,
      vectors for drug brain delivery using physiological approaches will be addressed.
      In addition to the Angiopep platform technology which is in development at
      Angiochem Inc. and is to date the most advanced in human clinical trials, the new
      Transcend technology using a protein melanotransferrin for the transport of
      biologics such as lysosomal enzymes and antibodies will be discussed.

PMID- 23171844
TI  - [Regulation of intercellular adhesion during epithelial morphogenesis].
AB  - The epithelium is one of the most abundant tissues in metazoans. It is required
      to generate stable chemical and mechanical barriers between physiological
      compartments (fluid matrix/external environment). This function is based on
      multiple intercellular junctions, which insulate and stabilize cell-cell contacts
      in the tissue. Despite this apparent robustness, epithelia can be extensively
      remodeled during wound healing, embryogenesis and tumor progression. The capacity
      to be remodeled while keeping tissue cohesion requires a perfect balance between
      stability and plasticity of intercellular junctions. The balance is partially
      regulated by intercellular adhesion, which is mostly based on adherens junctions
      and the transmembrane protein E-cadherin. The aim of this review is to report the
      molecular basis of the balance between plasticity and robustness in the
      epithelium. We will first present the minimal physical framework used to describe
      epithelial cell shape. We will then describe the main processes involved in
      intercellular adhesion regulation and their functions during epithelial
      morphogenesis. Eventually, we will analyze the relationship and the coupling
      between adhesive forces and cortical tension.

PMID- 23171845
TI  - Hepatitis E virus genotype 3 in shellfish, United Kingdom.

PMID- 23171846
TI  - A review of cognitive therapy in acute medical settings. Part I: therapy model
      and assessment.
AB  - INTRODUCTION: Although cognitive therapy (CT) has established outpatient utility,
      there is no integrative framework for using CT in acute medical settings where
      most psychosomatic medicine (P-M) clinicians practice. Biopsychosocial complexity
      challenges P-M clinicians who want to use CT as the a priori psychotherapeutic
      modality. For example, how should clinicians modify the data gathering and
      formulation process to support CT in acute settings? METHOD: Narrative review
      methodology is used to describe the framework for a CT informed interview,
      formulation, and assessment in acute medical settings. Because this review is
      aimed largely at P-M trainees and educators, exemplary dialogues model the
      approach (specific CT strategies for common P-M scenarios appear in the companion
      article.) RESULTS: Structured data gathering needs to be tailored by focusing on
      cognitive processes informed by the cognitive hypothesis. Agenda setting,
      Socratic questioning, and adaptations to the mental state examination are
      necessary. Specific attention is paid to the CT formulation, Folkman's Cognitive
      Coping Model, self-report measures, data-driven evaluations, and collaboration
      (e.g., sharing the formulation with the patient.) Integrative CT
      psychopharmacological approaches and the importance of empathy are emphasized.
      SIGNIFICANCE OF RESULTS: The value of implementing psychotherapy in parallel with
      data gathering because of time urgency is advocated, but this is a significant
      departure from usual outpatient approaches in which psychotherapy follows
      evaluation. This conceptual approach offers a novel integrative framework for
      using CT in acute medical settings, but future challenges include demonstrating
      clinical outcomes and training P-M clinicians so as to demonstrate fidelity.

PMID- 23171847
TI  - Dnmt1-dependent DNA methylation is essential for photoreceptor terminal
      differentiation and retinal neuron survival.
AB  - Epigenetic regulation of the genome is critical for the emergence of diverse cell
      lineages during development. To understand the role of DNA methylation during
      retinal network formation, we generated a mouse retinal-specific Dnmt1 deletion
      mutation from the onset of neurogenesis. In the hypomethylated Dnmt1-mutant
      retina, neural progenitor cells continue to proliferate, however, the cell cycle
      progression is altered, as revealed by an increased proportion of G1 phase cells.
      Despite production of all major retinal neuronal cell types in the Dnmt1-mutant
      retina, various postmitotic neurons show defective differentiation, including
      ectopic cell soma and aberrant dendritic morphologies. Specifically, the
      commitment of Dmnt1-deficient progenitors towards the photoreceptor fate is not
      affected by DNA hypomethylation, yet the initiation of photoreceptor
      differentiation is severely hindered, resulting in reduction and mislocalization
      of rhodopsin-expressing cells. In addition to compromised neuronal
      differentiation, Dnmt1 deficiency also leads to rapid cell death of
      photoreceptors and other types of neurons in the postnatal retina. These results
      indicate that Dnmt1-dependent DNA methylation is critical for expansion of the
      retinal progenitor pool, as well as for maturation and survival of postmitotic
      neurons.

PMID- 23171848
TI  - Dysregulation of core components of SCF complex in poly-glutamine disorders.
AB  - Poly-glutamine (polyQ) diseases are neurodegenerative disorders characterised by
      expanded CAG repeats in the causative genes whose proteins form inclusion bodies.
      Various E3 ubiquitin ligases are implicated in neurodegenerative disorders. We
      report that dysfunction of the SCF (Skp1-Cul1-F-box protein) complex, one of the
      most well-characterised ubiquitin ligases, is associated with pathology in polyQ
      diseases like Huntington's disease (HD) and Machado-Joseph disease (MJD). We
      found that Cullin1 (Cul1) and Skp1, core components of the SCF complex, are
      reduced in HD mice brain. A reduction in Cul1 levels was also observed in
      cellular HD model and fly models of both HD and MJD. We show that Cul1 is able to
      genetically modify mutant huntingtin aggregates because its silencing results in
      increased aggregate load in cultured cells. Moreover, we demonstrate that
      silencing dCul1 and dSkp1 in Drosophila results in increased aggregate load and
      enhanced polyQ-induced toxicity. Our results imply that reduced levels of SCF
      complex might contribute to polyQ disease pathology.

PMID- 23171849
TI  - JNK2 is activated during ER stress and promotes cell survival.
AB  - Adaptation to endoplasmic reticulum (ER) stress relies on activation of the
      unfolded protein response (UPR) and induction of autophagy. Indeed, cells die if
      ER stress is not countered by the UPR. Here we show in U937 cells that the ER
      stressors tunicamycin and thapsigargin cause increased expression of c-Jun N
      terminal kinase 2 (JNK2), which allows regulation of the UPR, whose silencing or
      pharmacological inhibition delays BiP (immunoglobulin heavy-chain binding
      protein) upregulation, and causes earlier and greater expression of
      CCAAT/enhancer-binding protein-homologous protein (CHOP). Furthermore, we show
      that pharmacological inhibition or silencing of JNK2 causes accumulation of both
      p62 and the acidic compartment, caspase 3 activation and apoptosis. Our results
      reveal that JNK2 prevents accumulation of the acidic compartment in U937 cells
      undergoing autophagic flux and, by this mechanism, it keeps stressed cells alive.
      Our findings highlight a potential role for JNK2 in tumor cell survival,
      senescence and neurodegenerative diseases, in which ER stress, autophagy and
      lysosome activity are known to interplay.

PMID- 23171850
TI  - JC-1: alternative excitation wavelengths facilitate mitochondrial membrane
      potential cytometry.
AB  - Mitochondrial membrane potential provides a valuable indicator of cells' health
      and functional status. Cytometry- and microscopy-based analyses, in combination
      with fluorescent probes, are widely used to study mitochondrial behavior related
      to cellular pathways, most notably - apoptosis. The cyanine dye JC-1 (5,5',6,6'
      tetrachloro-1,1',3,3'-tetraethylbenzimi- dazolylcarbocyanine iodide) facilitates
      discrimination of energized and deenergized mitochondria because the normally
      green fluorescent dye forms red fluorescent aggregates when concentrated in
      energized mitochondria in response to their higher membrane potential. JC-1
      fluorescence is usually excited by the 488 nm laser wavelength common in flow
      cytometers. In this study, we show that in practice this approach is not optimal
      for monitoring mitochondrial behavior. Investigation of fluorescence of JC-1 in
      solution and in cells using spectrofluorimetry, microscopy and flow cytometry
      reveals that excitation at 405 nm wavelength, now available on standard
      instruments, produces signals from aggregate fluorescence with considerably less
      spillover from dye monomer fluorescence than can be obtained using 488 nm
      excitation. The improved data are more accurate and eliminate the necessity for
      fluorescence compensation, making the use of the alternative excitation
      wavelengths beneficial for mitochondria-related biological and biomedial
      research.

PMID- 23171851
TI  - Histopathologic insight into saphenous vein bypass graft disease.
AB  - OBJECTIVES: Vein graft disease is a major drawback of coronary artery bypass
      grafting. However, histopathologic studies of old human aortocoronary grafts are
      scarce. METHODS: We screened patients undergoing redo coronary artery bypass
      grafting at three university hospitals and selected those with at least one
      excisable old vein graft. Native non-grafted saphenous veins were also obtained
      as controls. Clinical and angiographic data were separately documented. RESULTS:
      We evaluated 117 segments from 29 veins. All but 4 old graft segments showed
      degrees of luminal narrowing and fibrointimal proliferation. Moreover, 61
      segments demonstrated atherosclerotic plaques. Such plaques were typically
      concentric and, compared with other segments, more frequently represented
      necrosis, calcification and giant cells (p < 0.001 for all comparisons) and had a
      higher inflammatory cell count, predominantly of lymphocytic origin. Native
      saphenous veins frequently showed fibrosis, but no calcification or active
      inflammation. Angiographic findings showed moderate correlation with the
      histological degree of luminal stenosis (Spearman's rho = 0.564, p < 0.001).
      CONCLUSIONS: Human vein graft atherosclerosis and arterial atherosclerosis share
      many features; however, we found lymphocytes to be the dominant inflammatory
      cells within plaques. Conventional angiography underestimated the atherosclerosis
      burden in vein grafts. Improved understanding of disease pathophysiology could
      lead to the development of novel interventions that reduce costly and suboptimal
      repeat revascularizations.

PMID- 23171852
TI  - Effects of etomidate on complications related to intubation and on mortality in
      septic shock patients treated with hydrocortisone: a propensity score analysis.
AB  - INTRODUCTION: Endotracheal intubation in the ICU is associated with a high
      incidence of complications. Etomidate use is debated in septic shock because it
      increases the risk of critical illness-related corticosteroid insufficiency,
      which may impact outcome. We hypothesized that hydrocortisone, administered in
      all septic shock cases in our ICU, may counteract some negative effects of
      etomidate. METHODS: A single-center observational study was carried out in septic
      shock patients, treated with hydrocortisone and intubated within the first 48
      hours of septic shock. Co-primary end points were life-threatening complications
      incidence occurring within the first hour after intubation and mortality during
      the ICU stay. Statistical analyses included unmatched and matched cohorts using a
      propensity score analysis. P < 0.05 was considered significant. RESULTS: Sixty
      patients in the etomidate cohort and 42 patients in the non-etomidate cohort were
      included. Critical illness-related corticosteroid insufficiency was 79% in the
      etomidate cohort and 52% in the non-etomidate cohort (P = 0.01). After
      intubation, life-threatening complications occurred in 36% of the patients
      whatever the cohort. After adjustment with propensity score analysis, etomidate
      was a protective factor for death in the ICU both in unmatched (hazard ratio,
      0.33 (0.15 to 0.75); P < 0.01)) and matched cohorts (hazard ratio, 0.33 (0.112 to
      0.988); P = 0.04). CONCLUSION: In septic shock patients treated with
      hydrocortisone, etomidate did not decrease life-threatening complications
      following intubation, but when associated with hydrocortisone it also did not
      impair outcome.

PMID- 23171854
TI  - Neuroanesthesiology fellowship training: curricular guidelines from the Society
      for Neuroscience in Anesthesiology and Critical Care.
AB  - Standardization and accreditation of fellowship training have been considered in
      the field of neuroanesthesiology. A prior survey of members of the Society for
      Neuroscience in Anesthesiology and Critical Care (SNACC) suggested strong support
      for accreditation and standardization. In response, SNACC created a Task Force
      that developed curricular guidelines for neuroanesthesiology fellowship training
      programs. These guidelines represent a first step toward standards for
      neuroanesthesiology training and will be useful if accreditation is pursued in
      the future.

PMID- 23171853
TI  - Severity and persistence of asthma and mental health: a birth cohort study.
AB  - BACKGROUND: The goal of the current study was to investigate asthma and mental
      health among youth in the community, and to consider the role of asthma severity
      and persistence in this link. Method Data were drawn from the Raine Study, a
      population-based birth cohort study in Western Australia. Logistic regression
      models and generalized estimating equations were used to examine the relationship
      between asthma at age 5 years and the range of internalizing and externalizing
      mental health problems at ages 5-17 years. Analyses were stratified by asthma
      severity and persistence, and adjusted for a range of potential confounders.
      RESULTS: More severe and persistent asthma at age 5 was associated with
      significantly increased odds of affective, anxiety, somatic, oppositional defiant
      and conduct problems at ages 5-17. Mild asthma and remitted asthma were not
      associated with heightened vulnerability to mental disorders. CONCLUSIONS: Our
      results suggest that youth with symptomatic asthma are more likely to suffer from
      a wide range of mental health problems, and that the likelihood of mental health
      problems appears to increase as a function of asthma severity. Youth with poorly
      controlled and/or more severe and persistent asthma may be considered a
      vulnerable group who might benefit from mental health screening in clinical,
      school and community settings.

PMID- 23171855
TI  - Bone embolism during neurosurgery in sitting position.

PMID- 23171856
TI  - Association between CYP2C8 (rs1934951) polymorphism and bisphosphonate-related
      osteonecrosis of the jaws in patients on bisphosphonate therapy: a meta-analysis.
AB  - AIMS: Bisphosphonate-related osteonecrosis of the jaws (BONJ) is a severe
      complication in patients on bisphosphonate therapy. The study was conducted to
      verify the association between CYP2C8 (rs1934951) polymorphism and BONJ
      predisposition. METHODS: The relative epidemiologic studies were identified in
      PubMed and Embase to conduct a meta-analysis using STATA. RESULTS: In the pooled
      analysis with multiple cancer types, patients carrying the CYP2C8 rs1934951 AA or
      AG genotype showed no significantly increased BONJ susceptibility compared with
      those carrying the wild GG genotype [dominant: odds ratio (OR) = 2.05, 95%
      confidence interval (CI) = 0.67-6.29, p = 0.209; recessive: OR = 1.88, 95% CI =
      0.23-15.6, p = 0.560; AG vs. GG: OR = 2.07, 95% CI = 0.80-5.32, p = 0.133, and AA
      vs. GG: OR = 1.34, 95% CI = 0.48-3.74, p = 0.578]. A significant association
      between AA and AG genotypes of CYP2C8 (rs1934951) and BONJ risk was found in the
      subgroup analysis of multiple myeloma (dominant: OR = 5.77, 95% CI = 1.21-27.63,
      p = 0.028; AG vs. GG: OR = 5.02, 95% CI = 2.06-12.23, p = 0.001, and AA vs. GG:
      OR = 16.23, 95% CI = 1.72-78.7, p = 0.015). CONCLUSION: The results indicated
      that AA and AG genotypes of CYP2C8 (rs1934951) might be predictors for multiple
      myeloma patients at high risk to develop BONJ.

PMID- 23171857
TI  - Renoprotective effects of sildenafil in DOCA-salt hypertensive rats.
AB  - BACKGROUND/AIMS: Sildenafil, the first selective phosphodiesterase-5 (PDE5)
      inhibitor to be widely used for treating erectile dysfunction, has been
      investigated with regard to its cardioand renoprotective effects in animal
      models. This study further investigated the renoprotective effects of sildenafil
      and their molecular mechanisms in deoxycorticosterone acetate (DOCA)-salt
      hypertensive (DSH) rats. METHODS: DOCA strips (200 mg/kg) were implanted in rats
      1 week after unilateral nephrectomy. These rats were fed on a control diet, with
      or without sildenafil (50 mg.kg(-1)day(-1)), for 2 weeks. Systolic blood pressure
      (SBP) was measured by the tail cuff method, and the urinary albumin-to-creatinine
      ratio (ACR) was calculated. The extent of glomerulosclerosis and
      tubulointerstitial fibrosis was determined by Masson's trichrome stain. Renal
      expression of ED-1, transforming growth factor-beta1 (TGF-beta1), Bax, and Bcl-2
      were determined by semiquantitative immunoblotting, polymerase chain reaction
      (PCR), and immunohistochemistry. TUNEL staining was used for detecting apoptotic
      cells. RESULTS: The increased SBP in DSH rats was not attenuated by sildenafil
      treatment. The decreased creatinine clearance and increased ACR in DSH rats,
      compared with control animals, were attenuated by sildenafil treatment. Further,
      sildenafil treatment attenuated glomerulosclerosis and tubulointerstitial
      fibrosis in DSH rats and counteracted the increased expression of ED-1, TGF
      beta1, and Bax and the decreased expression of Bcl-2 in the kidneys of these
      rats. The increase in the number of apoptotic cells in DSH rats was attenuated by
      sildenafil treatment. CONCLUSION: Sildenafil effectively prevented the
      progression of renal injury in DSH rats via its anti-inflammatory, antifibrotic,
      and antiapoptotic effects.

PMID- 23171858
TI  - Are diabetes management guidelines applicable in 'real life'?
AB  - BACKGROUND: The American Diabetes Association (ADA) has published several
      diabetes treatment algorithms, but none have been tested in real-life settings.
      The aim of this study is to analyze the feasibility of achieving and/or
      maintaining HbA1c levels <7.0% using current diabetes treatment guidelines and
      the resources available in the public health care system of Brazil. METHODS: A
      one-year, single-arm interventional study was conducted with type 2 diabetes
      patients in a primary care unit. Intervention consisted of intensification of
      lifestyle changes and sequential prescription of drugs based on ADA guidelines
      using the medications available through the publicly funded Unified Health System
      (Sistema Unico de Saude, SUS). RESULTS: Ninety patients (age: 62.7+/-10.4 years;
      diabetes duration: 8.2+/-9.1 years) completed the trial. During the intervention
      period, increases were observed in number of oral antidiabetic agent (OAD)
      classes per patient (1.50+/-0.74 vs. 1.67+/-0.7; p=0.015), OAD pills per patient
      (2.64+/-1.89 vs. 3.33+/-2.23 pills/patient; p <0.001), insulin dosage (0.20+/
      0.29 vs.0.50+/-0.36 UI/kg/day; p=0.008) and number of patients on insulin (19
      [21%] vs. 31 [34%]; p<0.01), but no improvement in HbA1c (7.2+/-1.6% vs. 7.3+/
      1.5%; p=0.453) or frequency of patients on target, defined as HbA1c <7% (53.3%
      vs. 48.9%; p=0.655). Patients with baseline HbA1c <7% had a small increase in
      HbA1c during the trial (6.3+/-0.4 vs. 6.7+/-0.9%; p=0.002). No such change was
      observed in those with baseline HbA1c >=7%. CONCLUSIONS: In this group of
      patients with a mean baseline HbA1c of 7.2%, implementation of 2006/2009 ADA/EASD
      guidelines led to achievement of the therapeutic goal of HbA1c <7% in a small
      proportion of patients.

PMID- 23171859
TI  - Human microRNAs originated from two periods at accelerated rates in mammalian
      evolution.
AB  - MicroRNAs (miRNAs) are short, noncoding RNAs that modulate genes
      posttranscriptionally. Frequent gains and losses of miRNA genes have been
      reported to occur during evolution. However, little is known systematically about
      the periods of evolutionary origin of the present miRNA gene repertoire of an
      extant mammalian species. Thus, in this study, we estimated the evolutionary
      periods during which each of 1,433 present human miRNA genes originated within 15
      periods, from human to platypus-human common ancestral branch and a class
      "conserved beyond theria," primarily using multiple genome alignments of 38
      species, plus the pairwise genome alignments of five species. The results showed
      two peak periods in which the human miRNA genes originated at significantly
      accelerated rates. The most accelerated rate appeared in the period of the
      initial phase of hominoid lineage, and the second appeared shortly before
      Laurasiatherian divergence. Approximately 53% of the present human miRNA genes
      have originated within the simian lineage to human. In particular, approximately
      28% originated within the hominoid lineage. The early phase of placental mammal
      radiation comprises approximately 28%, while no more than 15% of human miRNAs
      have been conserved beyond placental mammals. We also clearly showed a general
      trend, in which the miRNA expression level decreases as the miRNA becomes
      younger. Intriguingly, amid this decreasing trend of expression, we found one
      significant rise in the expression level that corresponded to the initial phase
      of the hominoid lineage, suggesting that increased functional acquisitions of
      miRNAs originated at this particular period.

PMID- 23171860
TI  - Editor's Report for Volume 28 (2011).

PMID- 23171866
TI  - The synthesis of amines by the homogeneous hydrogenation of secondary and primary
      amides.

PMID- 23171862
TI  - Anisotropic isolation by distance: the main orientations of human genetic
      differentiation.
AB  - Genetic differentiation among human populations is greatly influenced by
      geography due to the accumulation of local allele frequency differences. However,
      little is known about the possibly different increment of genetic differentiation
      along the different geographical axes (north-south, east-west, etc.). Here, we
      provide new methods to examine the asymmetrical patterns of genetic
      differentiation. We analyzed genome-wide polymorphism data from populations in
      Africa (n = 29), Asia (n = 26), America (n = 9), and Europe (n = 38), and we
      found that the major orientations of genetic differentiation are north-south in
      Europe and Africa, and east-west in Asia, but no preferential orientation was
      found in the Americas. Additionally, we showed that the localization of the
      individual geographic origins based on single nucleotide polymorphism data was
      not equally precise along all orientations. Confirming our findings, we obtained
      that, in each continent, the orientation along which the precision is maximal
      corresponds to the orientation of maximum differentiation. Our results have
      implications for interpreting human genetic variation in terms of isolation by
      distance and spatial range expansion processes. In Europe, for instance, the
      precise northnorthwest-southsoutheast axis of main European differentiation
      cannot be explained by a simple Neolithic demic diffusion model without admixture
      with the local populations because in that case the orientation of greatest
      differentiation should be perpendicular to the direction of expansion. In
      addition to humans, anisotropic analyses can guide the description of genetic
      differentiation for other organisms and provide information on expansions of
      invasive species or the processes of plant dispersal.

PMID- 23171868
TI  - The effects of palmitic acid on nitric oxide production by rat skeletal muscle:
      mechanism via superoxide and iNOS activation.
AB  - BACKGROUND: Increased plasma concentrations of free fatty acids (FFA) can lead to
      insulin resistance in skeletal muscle, impaired effects on mitochondrial
      function, including uncoupling of oxidative phosphorylation and decrease of
      endogenous antioxidant defenses. Nitric oxide (NO) is a highly diffusible gas
      that presents a half-life of 5-10 seconds and is involved in several
      physiological and pathological conditions. The effects of palmitic acid on nitric
      oxide (NO) production by rat skeletal muscle cells and the possible mechanism
      involved were investigated. METHODS: Primary cultured rat skeletal muscle cells
      were treated with palmitic acid and NO production was assessed by nitrite
      measurement (Griess method) and 4,5-diaminofluorescein diacetate (DAF-2-DA)
      assay. Nuclear factor-kappa B (NF-KB) activation was evaluated by electrophoretic
      mobility shift assay and iNOS protein content by western blotting. RESULTS:
      Palmitic acid treatment increased nitric oxide production. This effect was
      abolished by treatment with NOS inhibitors, L-nitro-arginine (LNA) and L-nitro
      arginine methyl esther (L-NAME). NF-KB activation and iNOS content were increased
      due to palmitic acid treatment. The participation of superoxide on nitric oxide
      production was investigated by incubating the cells with DAF-2-DA in the presence
      or absence of palmitic acid, a superoxide generator system (X-XO), a mixture of
      NOS inhibitors and SOD-PEG (superoxide dismutase linked to polyethylene glycol).
      Palmitic acid and X-XO system increased NO production and this effect was
      abolished when cells were treated with NOS inhibitors and also with SOD-PEG.
      CONCLUSIONS: In summary, palmitic acid stimulates NO production in cultured
      skeletal muscle cells through production of superoxide, nuclear factor-kappa B
      activation and increase of iNOS protein content.

PMID- 23171869
TI  - Communication about psychotic symptoms in long-term psychiatric illness.
AB  - BACKGROUND: Communicating about psychotic symptoms can be challenging. This study
      aimed to identify (1) how psychiatrists and patients communicate about psychotic
      symptoms from a research and clinical perspective and (2) whether communication
      patterns depend on patients' symptom levels. SAMPLING AND METHODS: Consultations
      between 27 psychiatrists and 100 patients with long-term
      schizophrenia/schizoaffective disorder in outpatient clinics were video-recorded,
      transcribed and coded. Symptoms were assessed on the Positive and Negative
      Syndrome Scale. Avoidance or engagement with psychotic symptoms was coded
      separately by researchers and three clinical psychiatrists. RESULTS: Psychotic
      symptoms were not mentioned in 27% of consultations. Patients reported their
      absence in 34% of consultations and avoided talking about symptoms in 6%.
      Researchers rated psychiatrists as engaged in talking about psychotic symptoms in
      15% of consultations and avoiding talking about them in 18% of consultations.
      Psychiatrists identified somewhat less avoidance (10%) and more engagement (23%).
      Psychiatrist avoidance was seen when the patient raised the topic and the
      psychiatrist gave brief responses and/or changed the topic. When psychiatrists
      engaged, they asked specific questions about symptoms, responded to patient
      concerns and provided explanations about symptoms. Psychotic symptoms were more
      often discussed with patients with more negative and general symptoms.
      CONCLUSIONS: There is considerable variation in whether psychotic symptoms are
      discussed or not in outpatient consultations. Whether psychiatrists discuss
      psychotic symptoms is influenced by patients' symptoms; however, not by their
      psychotic symptoms but rather by the presence of negative and general symptoms.
      Psychiatrists' ratings of communication identify broadly similar patterns as
      detailed research analyses.

PMID- 23171870
TI  - Cohort profile: the MUg Observational Cohort.
AB  - Mildmay Uganda (MUg), an HIV treatment centre near Kampala, the capital of
      Uganda, has entered into a memorandum of understanding to collaborate with
      Canadian researchers at the University of Ottawa to develop their research
      programme and develop an observational cohort database (the MUg observational
      cohort). The primary objectives of the MUg observational cohort are to monitor
      clinical care and outcomes of HIV among patients on treatment and to bring
      awareness to trends that are functional and dysfunctional in HIV care in Uganda.
      The MUg observational cohort comprises 8835 individuals who initiated combination
      antiretroviral therapy at MUg between January 2004 and October 2011. There are
      considerably more women (63.2%) than men in the cohort, and age spans from
      newborn to 92 years old. The low median age of 31 years (interquartile range: 18
      38 years) can be explained by the 24.9% of the cohort aged <18 years. The median
      baseline CD4 cell count among the entire cohort is 172 cells/mm(3) (interquartile
      range: 73-249 cells/mm(3)). Data are routinely completed at treatment initiation,
      and follow-up data are collected routinely through physician visits and
      laboratory results. Data comprise demographic, behavioural and clinical
      variables. Collaborations and enquiries relating to the MUg observational cohort
      are encouraged, and can be addressed to Dr Edward Mills at
      edward.mills@uottowa.ca.

PMID- 23171872
TI  - Reliable plasmonic substrates for bioanalytical SERS applications easily prepared
      by convective assembly of gold nanocolloids.
AB  - The ability to easily prepare Surface Enhanced Raman Scattering (SERS) substrates
      by the assembly of chemically synthesized gold nanocolloids is of great interest
      for the advancement of SERS-based optical detection and identification of
      molecular species of biological or chemical interest, pollutants or warfare
      agents. In this work we employ three very simple strategies, which can be
      implemented in any laboratory without the need for specialized equipment, to
      prepare assemblies of citrate-stabilized spherical gold colloids: (i) drop
      coating, which induces the assembly of colloids in so-called coffee rings; (ii) a
      simplified variant of convective self-assembly (CSA), based on water evaporation
      in a constrained geometry, which yields highly uniform strips of nanoparticles
      (NP); (iii) assembly onto chemically functionalized glass surfaces which yields
      randomly assembled colloids and colloidal clusters. The SERS properties of the
      resulting colloidal assemblies are comparatively evaluated under multiple
      excitation lines with p-aminothiophenol (pATP) as a model Raman scatterer. The NP
      strips obtained by CSA prove to be SERS-active both in the visible and NIR and
      possess a highly uniform SERS response as demonstrated by spectra at individually
      selected sites and by confocal SERS mapping. Further it is shown that these NP
      strips are effective for the detection of cytosine, a DNA component, and for
      multi-analyte SERS detection. These results, showing how an efficient SERS
      substrate can be obtained by a very simple assembly method from easy-to
      synthesize colloidal gold NP, can have an impact on the development of analytical
      SERS applications.

PMID- 23171871
TI  - Cohort profile: the skin cancer after organ transplant study.
AB  - The Skin Cancer after Organ Transplant (SCOT) study was designed to investigate
      the link between genus beta human papillomavirus (HPV) and squamous cell skin
      cancer (SCSC). We focused on a population receiving immunosuppressive therapy for
      extended periods, transplant patients, as they are at extremely high risk for
      developing SCSC. Two complementary projects were conducted in the Seattle area:
      (i) a retrospective cohort with interview data from 2004 recipients of renal or
      cardiac transplants between 1995 and 2010 and (ii) a prospective cohort with
      interview data from 328 people on the transplant waiting lists between 2009 and
      2011. Within the retrospective cohort, we developed a nested case-control study
      (172 cases and 337 control subjects) to assess risk of SCSC associated with
      markers of HPV in SCSC tumour tissue and eyebrow hair bulb DNA (HPV genotypes)
      and blood (HPV antibodies). In the prospective cohort, 135 participants had a 1
      year post-transplant visit and 71 completed a 2-year post-transplant visit. In
      both arms of the cohort, we collected samples to assess markers of HPV infection
      such as acquisition of new types, proportion positive for each type, persistence
      of types at consecutive visits and number of HPV types detected. In the
      prospective cohort, we will also examine these HPV markers in relation to levels
      of cell-mediated immunity. The goal of the SCOT study is to use the data we
      collected to gain a more complete understanding of the role of immune suppression
      in HPV kinetics and of genus beta HPV types in SCSC. For more information, please
      contact the principal investigator through the study website:
      http://www.fhcrc.org/science/phs/cerc/The_SCOT_Study.html. 

PMID- 23171873
TI  - Individual and neighborhood socioeconomic status in relation to breast cancer
      incidence in African-American women.
AB  - Socioeconomic status (SES) for both individuals and neighborhoods has been
      positively associated with incidence of breast cancer, although not consistently.
      The authors conducted an assessment of these factors among African-American
      women, based on data from the Black Women's Health Study, a prospective cohort
      study of 59,000 African-American women from all regions of the United States.
      Individual SES was defined as the participant's self-reported level of education,
      and neighborhood SES was measured by a score based on census block group data for
      6 indicators of income and education. Analyses included 1,343 incident breast
      cancer cases identified during follow-up from 1995 through 2009. In age-adjusted
      analyses, SES for both individuals and neighborhoods was associated with an
      increased incidence of estrogen receptor-positive breast cancer. The associations
      were attenuated by control for parity and age at first birth, and there was no
      association after further control for other breast cancer risk factors. These
      findings suggest that the observed associations of breast cancer with SES may be
      largely mediated by reproductive factors that are associated with both estrogen
      receptor-positive breast cancer and SES.

PMID- 23171874
TI  - Dietary glycemic index and the risk of birth defects.
AB  - Prepregnancy diabetes and obesity have been identified as independent risk
      factors for several birth defects, providing support for a mechanism that
      involves hyperglycemia and hyperinsulinemia in the development of malformations.
      Data from the National Birth Defects Prevention Study from 1997 to 2007 were used
      to investigate the association between the maternal dietary glycemic index (DGI)
      and the risk of birth defects among nondiabetic women. DGI was categorized by
      using spline regression models and quartile distributions. Adjusted odds ratios
      and 95% confidence intervals were calculated. The joint effect of DGI and obesity
      was also examined. Among the 53 birth defects analyzed, high DGI, categorized by
      spline regression, was significantly associated with encephalocele (adjusted odds
      ratio (aOR) = 2.68), diaphragmatic hernia (aOR = 2.58), small intestinal
      atresia/stenosis (aOR = 2.97) including duodenal atresia/stenosis (aOR = 2.48),
      and atrial septal defect (aOR = 1.37). Using quartiles to categorize DGI, the
      authors identified associations with cleft lip with cleft palate (aOR = 1.23) and
      anorectal atresia/stenosis (aOR = 1.40). The joint effect of high DGI and obesity
      provided evidence of a synergistic effect on the risk of selected birth defects.
      High DGI is associated with an increased risk of a number of birth defects under
      study. Obesity coupled with high DGI appears to increase the risk further for
      some birth defects.

PMID- 23171875
TI  - Invited commentary: childhood acute lymphoblastic leukemia and allergies: biology
      or bias?
AB  - Previous epidemiologic studies have shown an inverse association between a
      personal history of atopy/allergies, both overall and among asthma, eczema, and
      hay fever investigated separately, and childhood acute lymphoblastic leukemia
      (ALL) with some consistency; however, in most of these studies, exposure data
      were collected by maternal interview. Now, in a population-based and records
      based study in this issue of the Journal (Am J Epidemiol. 2012;176(11):970-978),
      Chang et al. report an increased risk for allergic conditions across different
      etiologic time periods, calling the former paradigm into doubt. A review of the
      basic biology literature shows that proposed mechanisms support either a positive
      or an inverse association. In light of this ambiguity, it is epidemiology's turn
      to determine the direction of association.

PMID- 23171876
TI  - Allergy and risk of childhood acute lymphoblastic leukemia: a population-based
      and record-based study.
AB  - A deficit of normal immune stimulation in early childhood is a suspected risk
      factor for both childhood acute lymphoblastic leukemia (ALL) and allergies. The
      present study utilized a population-based case-control design using medical
      claims data from the National Health Insurance Research Database of Taiwan to
      evaluate the association between allergy and childhood leukemia. Eight hundred
      forty-six childhood ALL patients who were newly diagnosed during 2000 to 2008 and
      were older than 1 but less than 10 years of age were individually matched with
      3,374 controls based on sex, birth date, and time of diagnosis (reference date
      for the controls). Conditional logistic regression was performed to assess the
      association between childhood ALL and allergies. An increased risk of ALL was
      observed with having an allergy less than 1 year before the case's ALL diagnosis
      (odds ratio (OR) = 1.7, 95% confidence interval (CI): 1.5, 2.0), more than 1 year
      before the case's diagnosis (OR = 1.3, 95% CI: 1.1, 1.5), and before the age of 1
      year (OR = 1.4, 95% CI: 1.1, 1.7). These results suggest that the pathogenesis of
      childhood ALL and allergy share a common biologic mechanism.

PMID- 23171877
TI  - Stories from the evolution of guidelines for causal inference in epidemiologic
      associations: 1953-1965.
AB  - Guidelines for causal inference in epidemiologic associations were a major
      contribution to modern epidemiologic analysis in the 1960s. This story recounts
      dramatic elements in a series of exchanges leading to their formulation and
      effective use in the 1964 Report of the Advisory Committee to the US Surgeon
      General on Smoking and Health, the landmark report which concluded that cigarette
      smoking caused lung cancer. The opening salvo was precipitated by Ancel Keys'
      presentation of an ecologic correlation between diet and cardiac death, which was
      vigorously criticized in an article by Jacob Yerushalmy calling for "proper
      handling" of bias and confounding in observational evidence. The dispute
      demonstrated a need for guidelines for causal inference and set off their serial
      refinement among US thinkers. Less well documented parallel efforts went on in
      the United Kingdom, leading to the criteria that Bradford Hill presented in his
      1965 President's Address to the Royal Society of Medicine. Here the authors
      recount experiences with some of the principals involved in development of these
      criteria and note the omission from both classic reports of proper attribution to
      those who helped create the guidelines. They also present direct, if
      unsatisfying, evidence about those particular lapses.

PMID- 23171878
TI  - Invited commentary: circulating inflammation markers and cancer risk-
      implications for epidemiologic studies.
AB  - Chronic inflammation, an established risk factor for cardiovascular disease, is
      increasingly being recognized as an etiologic factor in several cancers. In this
      issue of the Journal, Touvier et al. (Am J Epidemiol. 2013;177(1):3-13) report on
      the association of 7 markers of inflammation, adiposity, and endothelial function
      with risk of overall cancer and breast and prostate cancers in a nested case
      control study carried out within the SU.VI.MAX cohort (France, 1994-2007).
      Consistent with previous reports on this topic, Touvier et al. focused on a
      limited number of markers. Future studies of inflammation and cancer should be
      able to capitalize on emerging multiplexed methods for the simultaneous detection
      of larger numbers of inflammatory markers in low-volume specimens. This should
      allow a more comprehensive evaluation of the role of inflammation in cancer
      development. In this commentary, the authors review emerging methods for
      measurement of multiplexed inflammation markers, the design and analytic
      implications of the use of these methods in epidemiologic studies, and potential
      public health implications of such studies. Given that many large prospective
      cohort studies have already collected and banked serum/plasma samples, rapid
      gains in our understanding of chronic inflammation and its role in cancer
      etiology are possible.

PMID- 23171880
TI  - Association between prediagnostic biomarkers of inflammation and endothelial
      function and cancer risk: a nested case-control study.
AB  - Experimental and prevalent case-control studies suggest an association between
      biomarkers of inflammation, endothelial function, and adiposity and cancer risk,
      but results from prospective studies have been limited. The authors' objective
      was to prospectively examine the relations between these biomarkers and cancer
      risk. A nested case-control study was designed within the Supplementation en
      Vitamines et Mineraux Antioxydants (SU.VI.MAX) Study, a nationwide French cohort
      study, to include all first primary incident cancers diagnosed between 1994 and
      2007 (n = 512). Cases were matched with randomly selected controls (n = 1,024) on
      sex, age (in 2-year strata), body mass index (weight (kg)/height (m)(2); <25 vs.
      >=25), and SU.VI.MAX intervention group. Conditional logistic regression was used
      to study the associations between prediagnostic levels of high-sensitivity C
      reactive protein (hs-CRP), adiponectin, leptin, soluble intercellular adhesion
      molecule 1 (sICAM-1), soluble vascular cell adhesion molecule 1, soluble E
      selectin, and monocyte chemoattractant protein 1 and cancer risk. All statistical
      tests were 2-sided. Plasma sICAM-1 level was positively associated with breast
      cancer risk (for quartile 4 vs. quartile 1, multivariate odds ratio (OR) = 1.86,
      95% confidence interval (CI): 1.06, 3.26; P(trend) = 0.048). Plasma hs-CRP level
      was positively associated with prostate cancer risk (for quartile 4 vs. quartile
      1, multivariate OR = 3.04, 95% CI: 1.28, 7.23; P(trend) = 0.03). These results
      suggest that prediagnostic hs-CRP and sICAM-1 levels are associated with
      increased prostate and breast cancer risk, respectively.

PMID- 23171881
TI  - Endometrial cancer risk factors by 2 main histologic subtypes: the NIH-AARP Diet
      and Health Study.
AB  - On the basis of clinical and pathologic criteria, endometrial carcinoma has been
      distinguished as types I (mainly endometrioid) and II (nonendometrioid). Limited
      data suggest that these subtypes have different risk factor profiles. The authors
      prospectively evaluated risk factors for types I (n = 1,312) and II (n = 138)
      incident endometrial carcinoma among 114,409 women in the National Institutes of
      Health (NIH)-AARP Diet and Health Study (1995-2006). For individual risk factors,
      relative risks were estimated with Cox regression by subtype, and
      P(heterogeneity) was assessed in case-case comparisons with type I as the
      referent. Stronger relations for type I versus Type II tumors were seen for
      menopausal hormone therapy use (relative risk (RR) of 1.18 vs. 0.84;
      P(heterogeneity) = 0.01) and body mass index of >=30 vs. <30 kg/m2 (RR of 2.93
      vs. 1.83; P(heterogeneity) = 0.001). Stronger relations for type II versus type I
      tumors were observed for being black versus white (RR of 2.18 vs. 0.66;
      P(heterogeneity) = 0.0004) and having a family history of breast cancer (RR of
      1.93 vs. 0.80; P(heterogeneity) = 0.002). Other risk factor associations were
      similar by subtype. In conclusion, the authors noted different risk factor
      associations for Types I and II endometrial carcinomas, supporting the etiologic
      heterogeneity of these tumors. Because of the limited number of Type II cancers,
      additional evaluation of risk factors will benefit from consortial efforts.

PMID- 23171882
TI  - Risk of total and aggressive prostate cancer and pesticide use in the
      Agricultural Health Study.
AB  - Because pesticides may operate through different mechanisms, the authors studied
      the risk of prostate cancer associated with specific pesticides in the
      Agricultural Health Study (1993-2007). With 1,962 incident cases, including 919
      aggressive prostate cancers among 54,412 applicators, this is the largest study
      to date. Rate ratios and 95% confidence intervals were calculated by using
      Poisson regression to evaluate lifetime use of 48 pesticides and prostate cancer
      incidence. Three organophosphate insecticides were significantly associated with
      aggressive prostate cancer: fonofos (rate ratio (RR) for the highest quartile of
      exposure (Q4) vs. nonexposed = 1.63, 95% confidence interval (CI): 1.22, 2.17;
      P(trend) < 0.001); malathion (RR for Q4 vs. nonexposed = 1.43, 95% CI: 1.08,
      1.88; P(trend) = 0.04); and terbufos (RR for Q4 vs. nonexposed = 1.29, 95% CI:
      1.02, 1.64; P(trend) = 0.03). The organochlorine insecticide aldrin was also
      associated with increased risk of aggressive prostate cancer (RR for Q4 vs.
      nonexposed = 1.49, 95% CI: 1.03, 2.18; P(trend) = 0.02). This analysis has
      overcome several limitations of previous studies with the inclusion of a large
      number of cases with relevant exposure and detailed information on use of
      specific pesticides at 2 points in time. Furthermore, this is the first time
      specific pesticides are implicated as risk factors for aggressive prostate
      cancer.

PMID- 23171884
TI  - Long-term association between leisure-time physical activity and changes in
      happiness: analysis of the Prospective National Population Health Survey.
AB  - Happiness is among the most fundamental of all human goals. Although the short
      term association between physical activity and happiness is well known, the long
      term associations are not. Data from the National Population Health Survey cycles
      conducted between 1994/1995 and 2008/2009 (cycles 1 through 8) were analyzed.
      Happy respondents were classified as physically active or inactive at baseline
      and then were followed up in subsequent cycles to examine their likelihood of
      becoming unhappy. Individuals who changed their activity level also were
      examined. After controlling for potential confounding factors, the authors found
      that leisure-time physical activity (LTPA) was associated with reduced odds of
      unhappiness after 2 years and 4 years. People who were inactive in 2 consecutive
      cycles were more than twice as likely to be unhappy as those who remained active
      in both cycles after 2 years. Compared with those who became active, inactive
      participants who remained inactive were also more likely to become unhappy. A
      change in LTPA from active to inactive was associated with increased odds of
      becoming unhappy 2 years later. This study suggests that LTPA has a long-term
      association with happiness. Changes in LTPA are associated with subsequent mood
      status.

PMID- 23171883
TI  - Perinatal and family risk factors for Hodgkin lymphoma in childhood through young
      adulthood.
AB  - The incidence of Hodgkin lymphoma has increased among adolescents and young
      adults in recent decades, but the relevant risk factors in early life are still
      unknown. A national cohort study was conducted of 3,571,574 individuals born in
      Sweden in 1973-2008 and followed up for Hodgkin lymphoma incidence through 2009,
      to examine perinatal and family risk factors for Hodgkin lymphoma in childhood
      through young adulthood (ages 0-37 years). There were 943 Hodgkin lymphoma cases
      identified in 66.3 million person-years of follow-up. High fetal growth was
      associated with an increased risk of Hodgkin lymphoma after adjustment for
      gestational age at birth and other potential confounders (P(trend) = 0.005).
      Family history of Hodgkin lymphoma in a sibling or parent also was strongly
      associated with an increased risk, with adjusted hazard ratios = 8.83 (95%
      confidence interval: 3.67, 21.30) and 7.19 (95% confidence interval: 3.58,
      14.44), respectively. No association was found between gestational age at birth,
      birth order, twinning, parental age, or parental education and Hodgkin lymphoma.
      These findings did not vary by age at Hodgkin lymphoma diagnosis. Similar
      associations were found for nodular sclerosis and mixed cellularity subtypes.
      These findings suggest that perinatal factors including possible growth factor
      pathways may contribute to the risk of Hodgkin lymphoma in childhood through
      young adulthood.

PMID- 23171885
TI  - Teaching cross-cultural aspects of mourning: a Hindu perspective on death and
      dying.

PMID- 23171886
TI  - [Virtual slides, yes, virtual pathologists, no!].

PMID- 23171887
TI  - [SAMHD1 deprives HIV of nucleotides, essential for viral DNA synthesis].

PMID- 23171888
TI  - [How human-specific SRGAP2 gene duplications control human brain development].

PMID- 23171889
TI  - [How epithelium gets rid of weird cells].

PMID- 23171890
TI  - [Targeting the appropriate body size].

PMID- 23171891
TI  - [How ApoE regulates blood-brain barrier integrity].

PMID- 23171892
TI  - [BCL11A controls the expression of the human fetal hemoglobin].

PMID- 23171893
TI  - [Structure of a bacterial nanomachine: the type 3 secretion system needle].

PMID- 23171894
TI  - [Colorectal cancer is typified by enhancer specific epigenetic mutations].

PMID- 23171895
TI  - [Neural interface systems: the future is (almost) here].

PMID- 23171896
TI  - [Optical remote control of native ion channels].

PMID- 23171897
TI  - [Born to smell].

PMID- 23171898
TI  - [Sphingosine 1-phosphate receptors: from biology to physiopathology].
AB  - Sphingosine 1-phosphate (S1P) mediates critical physiological responses by its
      binding to G protein-coupled receptor (GPCR) subtypes, known as S1P receptors.
      Five distinct mammalian S1P receptors, designated S1P1-5 have been identified,
      each with a different cellular pattern of expression which influences the
      responses to S1P. In this review, we briefly outline our understanding of the
      modes of action and the roles of S1P receptors in the regulation of physiological
      and pathological functions in the cardiovascular, immune and central nervous
      system.

PMID- 23171899
TI  - [Lineage fate decisions in normal and regenerating liver].
AB  - The origin of hepatocytes and cholangiocytes in embryonic and adult liver, as
      well as the source of stellate and sinusoidal cells, have received much attention
      recently, due to the availability of biological tools enabling to trace the fate
      of cell lineages. A model is now proposed which defines the differentiation
      potential of hepatoblasts, ductal plate cells and adult progenitor cells, in
      normal conditions and in regenerating liver. The mesodermal origin of stellate
      and sinusoidal cells is also established.

PMID- 23171901
TI  - [Implication of the ubiquitin ligase c-Cbl in bone formation and tumorigenesis].
AB  - Cbl ubiquitin ligases are important molecules that control the process of
      ubiquitination and degradation of proteins by the proteasome. Because this
      process regulates several intracellular mechanisms, alterations in Cbl activity
      lead to several pathologies including cancer. In bone, the c-Cbl ubiquitin ligase
      is known to control osteoclast activity. Our studies indicate that c-Cbl also
      regulates osteoblast proliferation, differentiation and survival. We recently
      showed that inhibition of c-Cbl activity using a c-Cbl mutant leads to promote
      osteoblast differentiation in mesenchymal stromal cells as a consequence of
      increased receptor tyrosine kinase expression. Conversely, we found that
      overexpression of c-Cbl leads to inhibit osteosarcoma cell proliferation and
      tumorigenesis through downregulation of these receptors. Thus, the use of
      pharmacological agents capable of modulating c-Cbl activity may be of therapeutic
      interest for promoting bone formation in normal bone, or to reduce tumorigenesis
      in primary bone cancer.

PMID- 23171900
TI  - [Chronic granulomatous disease: pathogenesis and therapy of associated fungal
      infections].
AB  - Chronic granulomatous disease is a genetic disorder responsible for a defect in
      the NADPH oxidase of phagocytic cells. It impairs the oxidative burst necessary
      to the intracellular inactivation of microorganisms and predisposes to an
      increased risk of infections by various microorganisms, including fungi like
      Aspergillus spp. and other less frequently encountered or emerging fungal
      species. Here we review the genetic basis, pathogenesis and clinical presentation
      associated with fungal infections in chronic granulomatous disease as well as the
      current prophylaxis and newly available therapies.

PMID- 23171902
TI  - [Whole slide imaging technology: from digitization to online applications].
AB  - As e-health becomes essential to modern care, whole slide images (virtual slides)
      are now an important clinical, teaching and research tool in pathology. Virtual
      microscopy consists of digitizing a glass slide by acquiring hundreds of tiles of
      regions of interest at different zoom levels and assembling them into a
      structured file. This gigapixel image can then be remotely viewed over a
      terminal, exactly the way pathologists use a microscope. In this article, we will
      first describe the key elements of this technology, from the acquisition, using a
      scanner or a motorized microscope, to the broadcasting of virtual slides through
      a local or distant viewer over an intranet or Internet connection. As virtual
      slides are now commonly used in virtual classrooms, clinical data and research
      databases, we will highlight the main issues regarding its uses in modern
      pathology. Emphasis will be made on quality assurance policies, standardization
      and scaling.

PMID- 23171903
TI  - [Telepathology with virtual slides].

PMID- 23171904
TI  - [The use of virtual slide for pedagogy].

PMID- 23171905
TI  - [Virtual slides in fundamental and clinical research].

PMID- 23171906
TI  - [The Eastern Quebec telepathology network: a real collective project].
AB  - The aim of the Eastern Quebec telepathology network is to provide uniform
      diagnostic telepathology services across a huge geographic region with a low
      population density. This project is intended to provide surgeons and pathologists
      with frozen section and second opinion services anywhere and at any time across
      the entire region, in order to avoid unnecessary patient transfer. The project
      has been implemented in 21 sites, each equipped with a whole slide scanner, a
      macroscopy station, a videoconferencing device and a viewer/case management and
      collaboration solution. Of the 21 sites, 6 are devoid of a pathology laboratory,
      two have no pathologist and 5 have only one pathologist on site. Signs of
      improvement of medical care in this region are already apparent since the Eastern
      Quebec telepathology network has been implemented. However, it is important not
      to underestimate the challenges related to change management in the course of
      implementation of such a new technology.

PMID- 23171907
TI  - [Story of the tomato through its genome].
AB  - Tomato (Solanum lycopersicum) is a model for fruit development. The tomato
      history has origins traced back to the early Aztecs. It was not until around the
      16(th) century that Europeans were introduced to this fruit, but only as
      ornamental plant since it was related to nightshade belladona. Then it was
      accepted into the kitchen all around the world. The genome sequence of the inbred
      cultivar Heinz 1706 is sequenced and provides interesting insights into the
      fleshy evolution.

PMID- 23171908
TI  - [Measles in France].
AB  - From January 2008 to May 2012, over 22,000 cases of measles were reported in
      France. The highest incidence rate was observed in children below one year of
      age. Over 50% of cases were reported in young adults. Almost 5,000 patients were
      hospitalised including 1,023 with severe pneumonia, 27 with encephalitis and/or
      myelitis : 10 died. This situation is linked to insufficient and heterogeneous
      vaccination coverage with pockets of susceptible people allowing virus
      circulation. Although the vaccine coverage in children has now improved for both
      doses, the issue of convincing young susceptible adults to catch up for measles
      vaccination remains critical, if the elimination target is to be met, and in
      order to protect the most vulnerable population unable to benefit from this
      vaccination (children below 1 year, immunodeficient people, pregnant women).

PMID- 23171910
TI  - [Novel ETO2-GLIS2 fusion and therapeutic strategy in acute megakaryoblastic
      leukemia].

PMID- 23171911
TI  - Effects of cortisol on memory in women with borderline personality disorder: role
      of co-morbid post-traumatic stress disorder and major depression.
AB  - BACKGROUND: Stress and cortisol administration are known to have impairing
      effects on memory retrieval in healthy humans. These effects are reported to be
      altered in patients with major depressive disorder (MDD) and post-traumatic
      stress disorder (PTSD) but they have not yet been investigated in borderline
      personality disorder (BPD). METHOD: In a placebo-controlled cross-over study, 71
      women with BPD and 40 healthy controls received either placebo or 10 mg of
      hydrocortisone orally before undertaking a declarative memory retrieval task
      (word list learning) and an autobiographical memory test (AMT). A working memory
      test was also applied. RESULTS: Overall, opposing effects of cortisol on memory
      were observed when comparing patients with controls. In controls, cortisol had
      impairing effects on memory retrieval whereas in BPD patients cortisol had
      enhancing effects on memory retrieval of words, autobiographical memory and
      working memory. These effects were most pronounced for specificity of
      autobiographical memory retrieval. Patients with BPD alone and those with co
      morbid PTSD showed this effect. We also found that co-morbid MDD influenced the
      cortisol effects: in this subgroup (BPD + MDD) the effects of cortisol on memory
      were absent. CONCLUSIONS: The present results demonstrate beneficial effects of
      acute cortisol elevations on hippocampal-mediated memory processes in BPD. The
      absence of these effects in patients with co-morbid MDD suggests that these
      patients differ from other BPD patients in terms of their sensitivity to
      glucocorticoids (GCs).

PMID- 23171913
TI  - Subjective health is likely to confound the association between will-to-live and
      survival.

PMID- 23171914
TI  - Severe neutropenia in patients with chronic hepatitis C: a benign condition.
AB  - BACKGROUND/AIMS: Patients with chronic hepatitis C virus (HCV) infection may
      develop neutropenia, which can delay or prevent treatment. Severe neutropenia,
      absolute neutrophil counts (ANC) <=0.500 * 10(9)/l, is a rare finding, with only
      two isolated reports published in the literature. The aim of this study was to
      evaluate the incidence and natural history of severe neutropenia in hepatitis C
      patients. METHODS: The records of 685 patients with active HCV were reviewed to
      identify those with severe neutropenia. The laboratory parameters and clinical
      history data of patients with severe neutropenia were then compared to a cohort
      of patients with HCV patients who had the more common minor neutropenia (ANC =
      1.000-1.500 10(9)/l). RESULTS: There was no significant difference in race, MELD
      (Model for End Stage Liver Disease) scores, portal hypertension, splenomegaly,
      viral load, viral type, or hemoglobin or platelet levels. Neither group suffered
      serious systemic infections. CONCLUSIONS: Severe neutropenia in HCV patients is
      underreported and not associated with serious HCV complications such as elevated
      MELD score or cirrhosis. Serious infection is rare and patients respond well to
      granulocyte colony-stimulating factor. Severely neutropenic patients with HCV
      appear to have a benign course and may be candidates for antiviral therapy.

PMID- 23171915
TI  - Job strain and incident metabolic syndrome over 5 years of follow-up: the
      coronary artery risk development in young adults study.
AB  - BACKGROUND: Theories of stress-induced metabolic syndrome predict that job strain
      would increase risk. Few studies have evaluated this association. OBJECTIVE: To
      evaluate the association between job strain and the risk of metabolic syndrome.
      METHODS: We investigated associations between job strain and incident metabolic
      syndrome adjusted for sociodemographic factors, health behaviors, and depressive
      symptoms over 5 years among 2966 black and white men and women in the Coronary
      Artery Risk Development in Young Adults study. Job strain was categorized by
      Karasek's model: high demands/low control; high demands/high control; low
      demands/low control; and low demands/high control. RESULTS: Compared with persons
      in low-strain jobs, men in active jobs (adjusted hazards ratio, 2.7; 95%
      confidence interval, 1.5 to 4.9) and women in high strain jobs (adjusted hazards
      ratio, 2.2; 95% confidence interval, 1.0 to 4.6) had significantly increased risk
      of metabolic syndrome. CONCLUSION: Job strain may be a modifiable risk factor for
      metabolic syndrome and subsequent cardiovascular disease.

PMID- 23171916
TI  - Predicting temporal trends in sickness absence rates for civil service employees
      of a federal public health agency.
AB  - OBJECTIVE: To determine whether trends of sickness in employees at a federal
      agency are predictable, and whether the variance was minimal enough to detect
      unusual levels of employee illness for further investigation. METHODS: Ten years
      of absenteeism data from an attendance system were analyzed for rates of sickness
      absence. Specifically, week of year and day of week were used to describe
      temporal trends. RESULTS: This study evaluates the predictability in temporal
      absence trends due to sickness among employees at a federal agency. Trends follow
      regular patterns during a given year that correspond to seasonal illnesses.
      Temporal trends in sick leave have been proven to be very predictable.
      CONCLUSION: The minimal variance allows the detection of sick leave anomalies
      that may be ascribable to specific causes, allowing the business or agency to
      follow-up and develop interventions.

PMID- 23171917
TI  - Brucellosis seroprevalence among workers in at-risk professions: northwestern
      Wyoming, 2005 to 2006.
AB  - OBJECTIVE: Brucellosis is uncommon in the United States; however, its circulation
      among wildlife and domestic cattle has been ongoing in Wyoming. To assess the
      public health threat of brucellosis circulation among animals, a seroprevalence
      study was undertaken among workers in professions considered to be at the highest
      risk for infection. METHODS: A seroprevalence study was undertaken targeting
      individuals in at-risk professions in the affected area of the state. RESULTS:
      Seroprevalence among study participants was 14.4%. Veterinarians were the main
      professional group that demonstrated a statistically significant association with
      measurable anti-Brucella antibodies. Vaccinating animals with Brucella vaccines
      was associated with seropositivity. CONCLUSION: The risk to the general public's
      health from the circulation of Brucella among wildlife and cattle can be
      attributed primarily to a limited subpopulation at high risk rather than a
      generally elevated risk.

PMID- 23171919
TI  - Venezuelan equine encephalitis virus glycoprotein pseudotyping confers
      neurotropism to lentiviral vectors.
AB  - We have produced high-titre HIV-1 green fluorescent protein-expressing lentiviral
      (LV) vectors pseudotyped with strain 3908 Venezuelan equine encephalitis virus
      glycoprotein (VEEV-G) and used them to study transduction of: (1) rat embryonic
      motor neuron (MN) and striatal neuron primary cultures, (2) differentiated MN
      cell line NSC-34 and (3) adult rat striatum. In primary neuronal cultures,
      transduction with VEEV-G-pseudotyped LV was more efficient and more neuronal than
      with vesicular stomatitis virus glycoprotein (VSV-G)-pseudotyped LV. In NSC-34
      cells clear retrograde transport of VEEV-G vector particles was observed. In the
      striatum at the injection site, transduction with the VEEV-G vectors driven by
      cytomegalovirus or phosphoglycerate kinase promoters exhibited a distinct
      neuronal tropism with no microglial and only a minor astroglial component,
      superior to that obtained with VSV-G-pseudotyped LV, irrespective of the promoter
      used. Neuronal transduction efficiency increased over time. Distal to the
      injection site transduction of mitral cells in the olfactory bulb, thalamic
      neurons and dopaminergic neurons in the substantia nigra pars compacta was
      detected. This, together with observations of retrograde axonal trafficking in
      vitro indicates that these vectors also possess low level of retrograde neuronal
      transduction capability in vivo. In this study, we demonstrate both strong
      neurotropism as well as sustainability of expression and minimal host immune
      response in vivo, making the VEEV-G-pseudotyped LV vectors potentially useful for
      gene therapy of neurodegenerative diseases. 

PMID- 23171918
TI  - A myeloid cell-binding adenovirus efficiently targets gene transfer to the lung
      and escapes liver tropism.
AB  - Specific and efficient gene delivery to the lung has been hampered by liver
      sequestration of adenovirus serotype 5 (Ad5) vectors. The complexity of Ad5 liver
      tropism has largely been unraveled, permitting improved efficacy of Ad5 gene
      delivery. However, Kupffer cell (KC) scavenging and elimination of Ad5 still
      represent major obstacles to lung gene delivery strategies. KC uptake
      substantially reduces bioavailability of Ad5 for target tissues and compensatory
      dose escalation leads to acute hepatotoxicity and a potent innate immune
      response. Here, we report a novel lung-targeting strategy through redirection of
      Ad5 binding to the concentrated leukocyte pool within the pulmonary
      microvasculature. We demonstrate that this leukocyte-binding approach retargets
      Ad5 specifically to lung endothelial cells and prevents KC uptake and hepatocyte
      transduction, resulting in 165,000-fold enhanced lung targeting, compared with
      Ad5. In addition, myeloid cell-specific binding is preserved in single-cell lung
      suspensions and only Ad.MBP-coated myeloid cells achieved efficient endothelial
      cell transduction ex vivo. These findings demonstrate that KC sequestration of
      Ad5 can be prevented through more efficient uptake of virions in target tissues
      and suggest that endothelial transduction is achieved by leukocyte-mediated 'hand
      off' of Ad.

PMID- 23171920
TI  - Understanding lentiviral vector chromatin targeting: working to reduce
      insertional mutagenic potential for gene therapy.
AB  - Replication-deficient retroviruses have been successfully utilized as vectors,
      offering an efficient, stable method of therapeutic gene delivery. Many examples
      exist proving this mode of integrative gene transfer is both effective and safe
      in cultured systems and clinical trials. Along with their success, severe side
      effects have occurred with early retroviral vectors causing a shift in the
      approach to vector design before further clinical testing. Several alternative
      delivery methods are available but lentiviral vectors (LV) are among the most
      favorable as they are already well understood. LV offer safer integration site
      selection profiles and a lower degree of genotoxicity, compared with gamma
      retroviral vectors. Following their introduction, development of the self
      inactivating vector configuration was a huge step to this mode of therapy but did
      not confer full protection against insertional mutagenesis. As a result
      integration, modeling must be improved to eventually avoid this possibility. The
      cellular factor LEDGF/p75 seems to play an essential role in the process of LV
      site selection and its interactions with chromatin are being quickly resolved.
      LEDGF/p75 is at the center of one example directed integration effort where
      recombinant products bias the integration event, a step toward fully directed
      integration into pre-determined benign loci. A more accurate picture of the
      details of LEDGF/p75 in the natural integration process is emerging, including
      new binding specificities, chromatin interaction kinetics and additional cellular
      factors. Together with next-generation sequencing technology and bio-informatics
      to analyze integration patterns, these advancements will lead to highly focused
      directed integration, accelerating wide-spread acceptance of LV for gene therapy.

PMID- 23171921
TI  - Effects of endothelin receptor antagonists on renal hemodynamics in angiotensin
      II-infused rats on high NaCl intake.
AB  - AIM: The aim was to investigate effects of selective endothelin (ET) receptor
      antagonists on renal hemodynamics and dynamic renal blood flow autoregulation
      (RBFA) in angiotensin II (Ang II)-infused rats on a high NaCl intake. METHODS:
      Sprague-Dawley rats received Ang II (250 ng/kg/min, s.c.) and an 8% NaCl diet for
      14 days after which renal clearance experiments were performed. After baseline
      measurements animals were administered either: (a) saline vehicle; (b) ETA
      receptor antagonist BQ-123 (30 nmol/kg/min); (c) ETB receptor antagonist BQ-788
      (30 nmol/kg/min); or (d) BQ-123 + BQ-788, for six consecutive 20-minute clearance
      periods. RESULTS: BQ-123 reduced arterial pressure (AP) and selectively increased
      outer medullary perfusion versus vehicle (p<0.05). These effects were attenuated
      or abolished by combined BQ-123 and BQ-788. BQ-788 reduced renal blood flow and
      increased renovascular resistance (p<0.05). Ang II-infused rats on high NaCl
      intake showed abnormalities in dynamic RBFA characterized by an impaired myogenic
      response that were not significantly affected by ET receptor antagonists.
      CONCLUSION: In hypertensive Ang II-infused rats on a high-NaCl intake selective
      ETA antagonism with BQ-123 reduced AP and specifically increased OM perfusion and
      these effects were dependent on intact ETB receptor stimulation. Furthermore, ET
      receptor antagonists did not attenuate abnormalities in dynamic RBFA.

PMID- 23171922
TI  - 9,10-Dihydroanthracenyl structures: original ligands for the synthesis of
      polymetallic complexes through selective pi-coordination.
AB  - N-Phenylsuccinimides and the corresponding pyrrolidines containing 9,10
      dihydroanthracenyl skeletons were used for exploring their ability to coordinate
      RuCp(+) moieties through the aromatic rings. Electronic and steric tuning of
      ligands led to mono-, bi- and tri-metallic complexes. A full structural study was
      carried out in order to characterize the ruthenium organometallic compounds,
      proving the different coordination modes both in solution (NMR) and in solid
      state (X-ray diffraction). A modelling study (at DFT level) was completed with
      the aim to understand the selective pi-coordination observed for mono- and bi
      metallic complexes.

PMID- 23171923
TI  - Water pipe smoking and its association with cigarette and cannabis use in young
      adults in Switzerland.
AB  - BACKGROUND: Water pipe is a traditional method of tobacco use, which is
      epidemically spreading throughout Europe. There are scarce data about the use of
      water pipe and its relation to other addictive behaviors among young adults in
      Western countries. OBJECTIVES: It was our aim to identify the sociodemographic
      characteristics of water pipe users in Switzerland and to describe concurrent
      cigarette and cannabis smoking habits. METHODS: Young adults aged 16-30 years
      were evaluated based on a 16-item standardized questionnaire on tobacco
      consumption and exhaled carbon monoxide. Current water pipe smoking was defined
      as water pipe use at least once within the last 4 weeks; regular water pipe
      smoking was defined as water pipe use at least once a week during the last 52
      weeks. RESULTS: Out of 353 volunteers, a total of 204 subjects (mean age 21 +/-
      3.5 years, 113 males) met the inclusion criteria for the study. A total of 78% (n
      = 160), 30.0% (n = 55) and 3.9% (n = 8) reported ever, current and regular water
      pipe smoking, respectively. Males smoked more often than females: 2.8
      sessions/year (interquartile range 1.1-8) versus 2 sessions/year (interquartile
      range 0-4; p = 0.022). The major risk factor for ever smoking water pipe was
      cigarette smoking (odds ratio 6.22, 95% confidence interval 2.33-16.62), followed
      by cannabis consumption (odds ratio 1.44, 95% confidence interval 1.29-1.62).
      Ever water pipe smoking was more common among current cannabis users (100 vs. 0%;
      p < 0.0001) and related to higher exhaled carbon monoxide values (6.0 +/- 9.0 vs.
      2.1 +/- 4.6 ppm; p < 0.001). CONCLUSION: Water pipe smoking is common among young
      adults and strongly associated with cigarette smoking and cannabis consumption.

PMID- 23171924
TI  - Bone marrow concentrate for autologous transplantation in minipigs.
      Characterization and osteogenic potential of mesenchymal stem cells.
AB  - Autologous bone marrow plays an increasing role in the treatment of bone,
      cartilage and tendon healing disorders. Cell-based therapies display promising
      results in the support of local regeneration, especially therapies using intra
      operative one-step treatments with autologous progenitor cells. In the present
      study, bone marrow-derived cells were concentrated in a point-of-care device and
      investigated for their mesenchymal stem cell (MSC) characteristics and their
      osteogenic potential. Bone marrow was harvested from the iliac crest of 16
      minipigs. The mononucleated cells (MNC) were concentrated by gradient density
      centrifugation, cultivated, characterized by flow cytometry and stimulated into
      osteoblasts, adipocytes, and chondrocytes. Cell differentiation was investigated
      by histological and immunohistological staining of relevant lineage markers. The
      proliferation capacity was determined via colony forming units of fibroblast and
      of osteogenic alkaline-phosphatase-positive-cells. The MNC could be enriched 3.5
      fold in nucleated cell concentrate in comparison to bone marrow. Flow cytometry
      analysis revealed a positive signal for the MSC markers. Cells could be
      differentiated into the three lines confirming the MSC character. The cellular
      osteogenic potential correlated significantly with the percentage of newly formed
      bone in vivo in a porcine metaphyseal long-bone defect model. This study
      demonstrates that bone marrow concentrate from minipigs display cells with MSC
      character and their osteogenic differentiation potential can be used for osseous
      defect repair in autologous transplantations.

PMID- 23171930
TI  - Routine screening for colon cancer after conservative treatment of
      diverticulitis.
AB  - BACKGROUND AND AIMS: It is generally advised to perform colonoscopy after
      conservatively treated diverticulitis because colon cancer may present itself
      with similar symptoms, laboratory and radiological results. With this study we
      investigated in what percentage of patients a malignancy was found by performing
      routine colonoscopy or radiologic imaging after a conservatively treated episode
      of diverticulitis, and whether this follow-up programme could be reserved for a
      selected group of patients. METHODS: In our hospital, routine colonoscopy or, as
      a second choice, radiologic imaging has been standard practice over the last
      decade. We collected all colonoscopy and radiologic imaging results that were
      conducted of all 516 patients who were diagnosed with diverticulitis in this
      period. RESULTS: Of those 516 patients, 378 had undergone colonoscopy, 45
      radiologic imaging and 93 did not undergo any additional investigation. Eight
      cases of malignant neoplasia were found in those patients (2.1%), and an
      additional number of 40 adenomatous polyps (9.5%). Six out of 8 patients with
      colon cancer reported rectal blood loss, significant weight loss or persisting
      abdominal pain after being treated for diverticulitis. CONCLUSIONS: In patients
      who were conservatively treated with routine colonoscopy or radiologic imaging
      for apparent diverticulitis, a malignant tumour was found in the colon in 2.1% of
      them. If only performed in patients reporting alarm symptoms, a case of colon
      cancer would be missed in only 0.5% of patients conservatively treated for
      diverticulitis. Therefore, screening for colon cancer after conservative
      treatment of diverticulitis is only indicated in symptomatic patients.

PMID- 23171931
TI  - Protection of DDAH2 overexpression against homocysteine-induced impairments of
      DDAH/ADMA/NOS/NO pathway in endothelial cells.
AB  - BACKGROUND/AIMS: Homocysteine-induced endothelial dysfunction favors the
      development of cardiovascular diseases through accumulation of endogenous nitric
      oxide (NO) synthase (NOS) inhibitor asymmetric dimethylarginine (ADMA).
      Dimethylarginine dimethylaminohydrolase 2 (DDAH2) is the major enzyme for the
      degradation of ADMA in endothelial cells. The purpose of this study was to
      determine whether suppressed DDAH2 expression contributed to impairments of
      DDAH/ADMA/NOS/NO pathway induced by homocysteine in endothelial cells and whether
      DDAH2 overexpression could prevent endothelial cell dysfunction caused by
      homocysteine. METHODS: Liposome-mediated transfection of endothelial cells was
      performed to establish the cell line of DDAH2 overexpression. After treatment of
      cells with 1 mmol/L homocysteine for 24 h, the transcription and expression of
      DDAH1 and DDAH2, DDAH and NOS activities as well as ADMA and NO concentrations
      were measured. RESULTS: Treatment of endothelial cells with homocysteine
      significantly suppressed the transcription and expression of DDAH2 but not DDAH1.
      This suppression was associated with the declined DDAH activity, increased ADMA
      accumulation, inhibited NOS activity and decreased NO production in endothelial
      cells. DDAH2 overexpression not only resisted homocysteine-induced decline of
      DDAH activity, but also decreased the accumulation of endogenous ADMA,
      subsequently attenuated the reductions of NOS activity and NO production induced
      by homocysteine. CONCLUSIONS: These results indicate that suppression of DDAH2
      expression is a culprit for homocysteine-induced impairments of DDAH/ADMA/NOS/NO
      pathway in endothelial cells, and therapeutic manipulation of DDAH2 expression
      may be a promising strategy for preventing endothelial dysfunction and
      cardiovascular diseases associated with hyperhomocysteinemia.

PMID- 23171932
TI  - Copper@carbon coaxial nanowires synthesized by hydrothermal carbonization process
      from electroplating wastewater and their use as an enzyme-free glucose sensor.
AB  - In the pursuit of electrocatalysts with great economic and ecological values for
      non-enzymatic glucose sensors, one-dimensional copper@carbon (Cu@C) core-shell
      coaxial nanowires (NWs) have been successfully prepared via a simple continuous
      flow wet-chemistry approach from electroplating wastewater. The as-obtained
      products were characterized by X-ray powder diffraction, scanning electron
      microscopy, transmission electron microscopy, selected area electron diffraction,
      energy dispersive X-ray spectroscopy and Raman spectroscopy. The electrocatalytic
      activity of the modified electrodes by Cu@C NWs towards glucose oxidation was
      investigated by cyclic voltammetry and chronoamperometry. It was found that the
      as-obtained Cu@C NWs showed good electrochemical properties and could be used as
      an electrochemical sensor for the detection of glucose molecules. Compared to the
      other electrodes including the bare Nafion/glassy carbon electrode (GCE) and
      several hot hybrid nanostructures modified GCE, a substantial decrease in the
      overvoltage of the glucose oxidation was observed at the Cu@C NWs electrodes with
      oxidation starting at ca. 0.20 V vs. Ag/AgCl (3 M KCl). At an applied potential
      of 0.65 V, Cu@C NWs electrodes had a high and reproducible sensitivity of 437.8
      uA cm(-2) mM(-1) to glucose. Linear responses were obtained with a detection
      limit of 50 nM. More importantly, the proposed electrode also had good stability,
      high resistance against poisoning by chloride ion and commonly interfering
      species. These good analytical performances make Cu@C NWs promising for the
      future development of enzyme-free glucose sensors.

PMID- 23171936
TI  - Donor and acceptor levels of organic photovoltaic compounds from first
      principles.
AB  - Accurate and efficient approaches to predict the optical properties of organic
      semiconducting compounds could accelerate the search for efficient organic
      photovoltaic materials. Nevertheless, predicting the optical properties of
      organic semiconductors has been plagued by the inaccuracy or computational cost
      of conventional first-principles calculations. In this work, we demonstrate that
      orbital-dependent density-functional theory based upon Koopmans' condition [Phys.
      Rev. B, 2010, 82, 115121] is apt for describing donor and acceptor levels for a
      wide variety of organic molecules, clusters, and oligomers within a few tenths of
      an electron-volt relative to experiment, which is comparable to the predictive
      performance of many-body perturbation theory methods at a fraction of the
      computational cost.

PMID- 23171937
TI  - Micrometastasis and skip metastasis as predictive factors in non-small-cell lung
      cancer staging.

PMID- 23171938
TI  - Mediastinal lymphadenectomy in elderly patients with non-small-cell lung cancer.
AB  - OBJECTIVES: The progressive ageing of the population is accompanied by an
      increasing incidence of cancer. Our objective was to compare mediastinal
      lymphadenectomy performed in the surgical treatment of non-small-cell lung cancer
      (NSCLC) patients between >= 70 and <70. METHODS: We performed a retrospective
      single-centre case-control study, including 80 patients >= 70 years of age,
      surgically treated for NSCLC between January 2008 and December 2010, matched 1:1
      to 80 younger controls on gender, American Society of Anesthesia score,
      performance status and histological subtype of the tumour. The number and type of
      dissected hilar/intrapulmonary and mediastinal lymph node stations as well as the
      number of resected lymph nodes were compared between the two age groups. RESULTS:
      The type of pulmonary resection was significantly different between the two
      groups (P = 0.03): pneumonectomy 6% (n = 5) for patients >= 70 vs 12% (n = 10)
      for patients <70, lobectomy 85 (n = 68) vs 65% (n = 52), bilobectomy 1 (n = 1) vs
      2% (n = 2) and sub-lobar resection 7 (n = 6) vs 20% (n = 16). There was no
      significant difference in type of mediastinal lymphadenectomy (radical vs
      sampling; P = 0.6). Elderly patients presented a more advanced N status of lymph
      node invasion than younger controls (P = 0.02). The number and type of dissected
      lymph node stations and the number of lymph nodes were not significantly
      different between the two age groups (P = 0.66 and 0.25, respectively). The mean
      number of metastatic lymph nodes was higher in patients >= 70 (2.3 vs 1.3 in
      patients <70; P = 0.002). Lymph node ratio between metastatic and resected lymph
      nodes was higher in elderly patients (0.11 vs 0.07 in younger controls; P =
      0.009). CONCLUSIONS: Lymph node involvement in surgically treated NSCLC was more
      significant in elderly patients >= 70 than in younger patients presenting
      comparable clinical and histopathological characteristics, and undergoing a
      similar lymphadenectomy.

PMID- 23171939
TI  - Gas in the superior mesenteric artery: severe malperfusion and bowel necrosis
      caused by acute aortic dissection.

PMID- 23171940
TI  - Adenosine injection prior to cardioplegia enhances preservation of senescent
      hearts in rat heterotopic heart transplantation.
AB  - OBJECTIVES: Advanced donor age is one of the risk factors for graft failure and
      is the leading cause of early death after heart transplantation. Better
      myocardial preservation methods should reduce graft failure. The purpose of this
      study was to determine if adenosine, which is known to enhance cardioplegic
      protection, enhances myocardial preservation during heart transplantation using
      older donors. METHODS: We used a rat heterotopic heart transplantation model with
      Lewis rats that were at least 60 weeks old as donors. We injected saline
      (control) or adenosine (0.1 or 0.2 mg/kg) before cardioplegia, perfused with cold
      Celsior and stored the hearts in Celsior for 6 h at 4 degrees C. The grafts were
      transplanted into syngenic, 12-16-week old recipients, and blood and tissue were
      collected 3 h after reperfusion. RESULTS: Bolus injection of adenosine led to
      faster mechanical arrest after perfusion with Celsior and faster reanimation
      after reperfusion compared with controls. Adenosine treatment significantly
      reduced myocardial injury, as indicated by serum troponin I and creatine
      phosphokinase levels. The mRNAs for inflammatory cytokines were markedly
      increased in the control grafts, but were less upregulated in the grafts treated
      with adenosine. The grafts treated with adenosine also exhibited less
      mitochondrial damage, fewer infiltrating cells and a higher adenosine
      triphosphate content. CONCLUSIONS: Adenosine injection prior to perfusion of
      cardioplegia significantly reduced cold ischaemia/reperfusion injury in cardiac
      grafts from older donors and improved the stores of cellular energy after
      reperfusion. This procurement protocol may be clinically feasible and should be
      considered in the clinical setting, particularly for older donors.

PMID- 23171941
TI  - Visualization of hypoxemic coronary perfusion despite full retrograde
      extracorporeal circulatory life support.

PMID- 23171942
TI  - Reply to Krueger et al.

PMID- 23171943
TI  - Clopidogrel and aspirin administration management prior to coronary artery
      surgery requires an individual approach.

PMID- 23171948
TI  - miR-148b functions as a tumor suppressor in pancreatic cancer by targeting
      AMPKalpha1.
AB  - miRNAs are small noncoding RNAs that participate in a variety of biologic
      processes, and dysregulation of miRNA is always associated with cancer
      development and progression. Aberrant expression of miR-148b has been found in
      some types of cancer, but its expression and potential biologic role in
      pancreatic cancer are still largely unknown. In this study, our data showed that
      miR-148b was significantly downregulated in 48 pairs of human pancreatic cancer
      tissues and five cell lines. Furthermore, the deregulated miR-148b was correlated
      with increased tumor size, late tumor-node-metastasis stage, lymphatic invasion,
      distant metastasis, and worse prognosis in pancreatic cancer. Functional studies
      indicated overexpression of miR-148b dramatically suppressed the growth of cancer
      cells, attributable to induction of apoptosis and cell-cycle arrest at S-phase.
      Meanwhile, miR-148b remarkably inhibited invasion and enhanced chemosensitivity
      of pancreatic cancer cells. Moreover, ectopic expression of miR-148b was able to
      inhibit tumorigenicity in nude mice. Further studies revealed that AMPKalpha1
      might be the direct target gene of miR-148b, and overexpressed AMPKalpha1
      inversely correlated with miR-148b in pancreatic cancer. Silencing of AMPKalpha1
      with RNA interference inhibited the growth of pancreatic cancer cells in vitro
      and in vivo and also induced apoptosis, cell-cycle arrest, and inhibited invasion
      of cancer cells, which is consistent with the effects of miR-148b overexpression.
      In conclusion, miR-148b can inhibit cell proliferation, invasion, and enhance
      chemosensitivity of pancreatic cancer by targeting AMPKalpha1. Our present
      results implicate the potential effects of miR-148b on prognosis and treatment of
      pancreatic cancer.

PMID- 23171949
TI  - Genome and transcriptome sequencing in prospective metastatic triple-negative
      breast cancer uncovers therapeutic vulnerabilities.
AB  - Triple-negative breast cancer (TNBC) is characterized by the absence of
      expression of estrogen receptor, progesterone receptor, and HER-2. Thirty percent
      of patients recur after first-line treatment, and metastatic TNBC (mTNBC) has a
      poor prognosis with median survival of one year. Here, we present initial
      analyses of whole genome and transcriptome sequencing data from 14 prospective
      mTNBC. We have cataloged the collection of somatic genomic alterations in these
      advanced tumors, particularly those that may inform targeted therapies. Genes
      mutated in multiple tumors included TP53, LRP1B, HERC1, CDH5, RB1, and NF1.
      Notable genes involved in focal structural events were CTNNA1, PTEN, FBXW7,
      BRCA2, WT1, FGFR1, KRAS, HRAS, ARAF, BRAF, and PGCP. Homozygous deletion of
      CTNNA1 was detected in 2 of 6 African Americans. RNA sequencing revealed
      consistent overexpression of the FOXM1 gene when tumor gene expression was
      compared with nonmalignant breast samples. Using an outlier analysis of gene
      expression comparing one cancer with all the others, we detected expression
      patterns unique to each patient's tumor. Integrative DNA/RNA analysis provided
      evidence for deregulation of mutated genes, including the monoallelic expression
      of TP53 mutations. Finally, molecular alterations in several cancers supported
      targeted therapeutic intervention on clinical trials with known inhibitors,
      particularly for alterations in the RAS/RAF/MEK/ERK and PI3K/AKT/mTOR pathways.
      In conclusion, whole genome and transcriptome profiling of mTNBC have provided
      insights into somatic events occurring in this difficult to treat cancer. These
      genomic data have guided patients to investigational treatment trials and provide
      hypotheses for future trials in this irremediable cancer.

PMID- 23171950
TI  - Candidacidal effect of fluconazole and chlorhexidine released from acrylic
      polymer.
AB  - OBJECTIVES: To investigate the efficacy and rate of killing of a fluconazole- or
      chlorhexidine-impregnated polymeric delivery system against fluconazole
      susceptible and -resistant Candida albicans and fluconazole-resistant Candida
      glabrata. METHODS: Poly(ethyl methacrylate)/tetrahydrofurfuryl methacrylate
      (PEM/THFM) discs impregnated with chlorhexidine, pure fluconazole (FLCp) or
      fluconazole from capsules (FLCc) were prepared by substituting a portion of PEM
      powder with an equivalent amount of each drug. Discs were incubated in sterile
      water for 1, 3, 7, 14, 21 and 28 days. The amounts of drugs in the leachates were
      measured spectrophotometrically and their antifungal activity against fluconazole
      susceptible (n=1) and fluconazole-resistant (n=2) candidal isolates was
      determined using a time-kill method and by comparing the released concentrations
      with the corresponding MICs. RESULTS: Fluconazole and chlorhexidine leached from
      PEM/THFM polymer for up to 28 days and the released concentrations were
      fungicidal against all three Candida isolates for at least the first 7 days.
      Chlorhexidine leachates killed all Candida isolates more rapidly than the two
      fluconazole formulation leachates throughout the study period. FLCc leachates
      required longer incubation for 100% killing than FLCp leachates. The proportion
      of viable C. glabrata dropped more slowly than that of C. albicans with the same
      MIC. CONCLUSIONS: The concentrations of chlorhexidine and fluconazole leached
      from the PEM/THFM polymer were fungicidal against all Candida isolates, including
      those resistant to fluconazole, for the first 7 days. Chlorhexidine leachates
      showed a rapid fungicidal activity for up to 4 weeks, which can be of use in
      cases with poor response to conventional antifungals.

PMID- 23171951
TI  - A new workflow for the microbiological diagnosis of febrile neutropenia in
      patients with a central venous catheter.
AB  - OBJECTIVES: We aimed to improve the microbial diagnosis of first episodes of
      febrile neutropenia (FEFNs) since <30% of episodes are microbiologically
      documented. Consequently patients are usually treated by empirical antibiotic
      therapy. METHODS: A prospective study evaluated a new workflow combining: (i) one
      40 mL blood culture (BC) sampled from the central venous catheter; (ii) immediate
      incubation in an automated BC system on the ward; (iii) direct detection of
      microbial DNA in blood; and (iv) identification and susceptibility testing using
      rapid methods performed directly on positive BC bottles. Patients were also
      sampled for the standard workflow with two BC sets incubated in the central
      laboratory and assessed by classical procedures. RESULTS: One hundred and twenty
      consecutive FEFNs were included (February 2008-March 2009). The new workflow was
      as sensitive as the standard workflow, with BC positivity rates of 30% (36/120)
      and 28% (34/120), respectively (McNemar's chi(2) =0.67, P=0.41). Direct DNA
      detection was positive in nine episodes (7.5%) that were also positive in BC. The
      new workflow provided microbiological results significantly earlier than the
      standard workflow, with a shorter time to BC positivity (median 12 h 31 min,
      range 7 h 55 min-25 h 37 min versus median 13 h 01 min, range 9 h 31 min-43 h 33
      min, P=0.004) and shorter turnaround times for identification and susceptibility
      testing, with most of the results obtained <24 h after BC sampling. We
      retrospectively estimated that the new workflow would lead to earlier adequacy of
      antimicrobial therapy in 30% of documented cases. CONCLUSIONS: Our new process
      improved the microbiological diagnosis in FEFNs. Cost effectiveness needs to be
      tested.

PMID- 23171952
TI  - Laparoscopic excision of gastric mass yields intra-abdominal esophageal
      duplication cyst.
AB  - A 69-year-old man with presumed solid gastric mass determined by computed
      tomography, endoscopic ultrasonography, and fine-needle aspiration underwent
      videoscopic excision of what resulted in a cystic structure consistent with intra
      abdominal esophageal duplication cyst. Esophageal duplication cysts are rare
      congenital lesions that are difficult to diagnose. They seldom occur entirely
      below the diaphragm, and occurrence in adults is unusual. Only six such cases are
      reported in the literature. When diagnosis is made, treatment decisions are not
      always straight forward, although excision is frequently pursued. The current
      case describes this unique finding and presents laparoscopic excision as a safe
      treatment alternative. 

PMID- 23171953
TI  - A combination of healthy lifestyle factors is associated with a decreased
      incidence of chronic kidney disease: a population-based cohort study.
AB  - A combination of healthy lifestyle factors is associated with lower risks of
      coronary heart disease, diabetes and stroke, but little is known about its
      association with chronic kidney disease (CKD). This study analyzed the effect of
      a combination of healthy lifestyle factors on the incidence of proteinuria among
      participants without CKD. Of the 7565 persons aged 40-79 years who participated
      in the Specific Health Checkups and Guidance System in Sado Island, Japan in
      2008, 4902 participants (2015 males) without CKD were included. The healthy
      lifestyle score was calculated by summing the total number of lifestyle factors
      for which the participants were at low risk. Low risk was defined as (1)
      nonsmoker, (2) body mass index (BMI) <25 kg m(-2), (3) moderate or less alcohol
      consumption, (4) regular exercise and (5) better eating patterns. Logistic
      analysis was used to examine the relationship between the baseline score in 2008
      and the development of proteinuria in 2009. Proteinuria developed in 2.2% of
      participants (males, 3.2; females, 1.5%). Compared with participants with a
      healthy lifestyle score of 0 to 2, participants with a score of 5 had a lower
      risk (odds ratio: 0.39, 95% confidence interval: 0.16-0.94), independently of
      having diabetes, hypertension and hypercholesterolemia. Overall, 47% of the cases
      in this cohort could be attributed to lack of adherence to this low-risk pattern.
      These findings underscore the importance of a healthier lifestyle in preventing
      CKD.

PMID- 23171954
TI  - Mineralocorticoid receptor antagonists: their use and differentiation in Japan.
AB  - In the presence of salt, aldosterone causes hypertension and organ damage via the
      mineralocorticoid receptor (MR) through various mechanisms. MR antagonists are
      considered to be potassium-sparing diuretics that exert their effect by blocking
      MR in the kidney, and they are not the first choice for treating hypertension.
      However, the importance and usefulness of inhibiting aldosterone in the
      management of hypertension have recently been revealed in both the basic and
      clinical fields. In Japan, both the selective MR antagonist eplerenone and the
      non-selective MR antagonist spironolactone are indicated for the treatment of
      hypertension. Although these drugs are generally used in the same manner, in some
      cases they require differentiation. This differentiation is divided into two
      types due to the differences in their features and differences in their
      contraindications in Japan. Based on a number of studies on MR antagonists that
      have been recently published, the diseases and clinical conditions targeted by MR
      antagonists appear to be likely to increase in the future. In Japan, we consider
      it necessary to carefully differentiate spironolactone from eplerenone in regard
      to their intended uses.

PMID- 23171955
TI  - How important is it to control nocturnal hypertension with angiotensin II type 1
      receptor blockers?

PMID- 23171956
TI  - Stroke awareness in two Estonian cities: better knowledge in subjects with
      advanced age and higher education.
AB  - OBJECTIVES: This study was undertaken to assess stroke awareness of the Estonian
      population. METHODS: Investigators were asked to fill in an original, closed
      ended multiple-choice questionnaire about the definition, risk factors, symptoms
      and behavior at the onset of stroke by randomly selected subjects in public
      places of the two biggest cities in Estonia (Tallinn and Tartu). RESULTS: The
      study included 355 persons. Most of the respondents knew that stroke is an acute
      disease and that one should call the ambulance at the onset of a stroke. Speech
      disorder and paresis were the best known symptoms, while hypertension was the
      best known risk factor. There were no differences between the sexes, but advanced
      age and higher level of education were related to higher awareness. CONCLUSIONS:
      The overall knowledge was better compared to many other studies. Future awareness
      campaigns should be addressed to younger subjects with lower education.

PMID- 23171957
TI  - In vitro  radiographic characteristics and biomechanical properties of the canine
      lumbar vertebral motion unit after lateral corpectomy, mini-hemilaminectomy and
      hemilaminectomy.
AB  - OBJECTIVE: The purpose of this study was to assess the effect of three surgical
      procedures (left lateral corpectomy [LC], LC plus mini-hemilaminectomy [LC-MH],
      and LC plus hemilaminectomy [LC-H]) on the biomechanics and intervertebral
      collapse of a lumbar vertebral motor unit (VMU). METHODS: Six canine cadaveric
      first and second lumbar vertebrae (L1-L2) VMU were retrieved. Range-of-motion
      (ROM) was measured while a custom-built mechanical simulator applied 3 Nm torque
      in lateral bending, flexion and extension to the intact VMU and following the
      three surgical procedures (LC, LC-MH, LC-H) performed sequentially. Radiographs
      were taken with and without 3 kg axial compression at each step. RESULTS: Left
      lateral corpectomy and LC-MH significantly increased the ROM in left lateral
      bending and total lateral bending. A LC-H significantly increased the ventral,
      left, right, total lateral, and total dorsoventral ROM. Significant
      intervertebral collapse was observed after LC-H with and without axial
      compression, and after LC and LC-MH, but only with axial compression. CLINICAL
      SIGNIFICANCE: A LC induces significantly increased ROM in lateral bending to the
      side of the surgery and in total lateral ROM. Extending the LC to a LC-MH does
      not change the spinal column stability compared to LC alone, while it provides
      better access to the spinal canal. The LC-H further destabilizes the VMU. The
      finding of intervertebral collapse following these surgical procedures confirms
      the importance of the intervertebral disc and articular facet in the maintenance
      of spatial integrity.

PMID- 23171958
TI  - Real-time isothermal RNA amplification of toxic marine microalgae using preserved
      reagents on an integrated microfluidic platform.
AB  - Quantitation of specific RNA sequences is a useful technique in marine biology
      that can elucidate cell abundance, speciation and viability, especially for early
      detection of harmful algal blooms. We are thus developing an integrated
      microfluidic system for cell concentration and lysis, RNA extraction/purification
      and quantitative RNA detection for environmental applications. The portable
      system is based on a microfluidic cartridge, or "lab-card", using a low-cost
      injection moulded device, with a laminated lid. Here we present real-time
      isothermal RNA amplification using reagent master-mixes preserved on-chip in a
      gel at 4  degrees C for up to eight months. We demonstrate quantitation by
      reference to an internal control in a competitive assay with 500 cell equivalents
      of the toxic microalga Karenia brevis. Annealing of primers, amplification at 41 
      degrees C and real-time fluorescence detection of the internal control and target
      using sequence-specific molecular beacons were all performed on-chip.

PMID- 23171959
TI  - Effective induction therapy with subcutaneous administration of bortezomib for
      newly diagnosed POEMS syndrome: a case report and a review of the literature.
AB  - POEMS syndrome is characterized by polyneuropathy, organomegaly, endocrinopathy,
      monoclonal gammopathy and skin changes. Bortezomib is an important component of
      the chemotherapy regimen associated with multiple myeloma, and has been
      previously applied to POEMS syndrome. We present a 56-year-old Chinese man who
      was given subcutaneous administration of bortezomib as part of the BDex
      (bortezomib-dexamethasone) regimen for his POEMS syndrome. The peripheral
      neuropathy and laboratory-test results of the patient improved dramatically with
      4 cycles of treatment, resulting in a complete response. In addition, the
      treatment was well tolerated and adequate peripheral blood hematopoietic stem
      cells were collected for an ensuing autologous stem cell transplant.

PMID- 23171961
TI  - Toll-like receptor 4 in experimental kidney transplantation: early mediator of
      endogenous danger signals.
AB  - The role of toll-like receptors (TLRs) has been described in the pathogenesis of
      renal ischemia/reperfusion injury, but data on the expression and function of
      TLR4 during renal allograft damage are still scarce. We analyzed the expression
      of TLR4 in an experimental rat model 6 and 28 days after allogeneic kidney
      transplantation in comparison to control rats and rats after syngeneic
      transplantation. On day 6, a significant induction in TLR4 expression--restricted
      to the glomerular compartment--was found in acute rejecting allografts only. TLR4
      expression strongly correlated with renal function, and TLR4 induction was
      accompanied by a significant increase in CC chemokine expression within the graft
      as well as in urinary CC chemokine excretion. TLR4 induction may be caused by an
      influx of macrophages as well as TLR4-expressing intrinsic renal cells.
      Fibrinogen deposition in renal allografts correlated with renal TLR4 expression
      and may act as a potent stimulator of chemokine release via TLR4 activation. This
      study provides, for the first time, data about the precise intrarenal
      localization and TLR4 induction after experimental kidney transplantation. It
      supports the hypothesis that local TLR4 activation by endogenous ligands may be
      one pathological link from unspecific primary allograft damage to subsequent
      chemokine release, infiltration and activation of immune cells leading to
      deterioration of renal function and induction of renal fibrosis.

PMID- 23171960
TI  - SGK3 regulates Ca(2+) entry and migration of dendritic cells.
AB  - BACKGROUND/AIMS: Dendritic cells (DCs) are antigen-presenting cells linking
      innate and adaptive immunity. DC maturation and migration are governed by
      alterations of cytosolic Ca(2+) concentrations ([Ca(2+)](i)). Ca(2+) entry is in
      part accomplished by store-operated Ca(2+) (SOC) channels consisting of the
      membrane pore-forming subunit Orai and the ER Ca(2+) sensing subunit STIM.
      Moreover, DC functions are under powerful regulation of the phosphatidylinositol
      3-kinase (PI3K) pathway, which suppresses proinflammatory cytokine production but
      supports DC migration. Downstream targets of PI3K include serum- and
      glucocorticoid-inducible kinase isoform SGK3. The present study explored, whether
      SGK3 participates in the regulation of [Ca(2+)](i) and Ca(2+)-dependent functions
      of DCs, such as maturation and migration. METHODS/RESULTS: Experiments were
      performed with bone marrow derived DCs from gene targeted mice lacking SGK3
      (sgk3(-/-)) and DCs from their wild type littermates (sgk3(+/+)). Maturation,
      phagocytosis and cytokine production were similar in sgk3(-/-) and sgk3(+/+) DCs.
      However, SOC entry triggered by intracellular Ca(2+) store depletion with the
      endosomal Ca(2+) ATPase inhibitor thapsigargin (1 uM) was significantly reduced
      in sgk3(-/-) compared to sgk3(+/+) DCs. Similarly, bacterial lipopolysaccharide
      (LPS, 1 ug/ml)- and chemokine CXCL12 (300 ng/ml)- induced increase in [Ca(2+)](i)
      was impaired in sgk3(-/-) DCs. Moreover, currents through SOC channels were
      reduced in sgk3(-/-) DCs. STIM2 transcript levels and protein abundance were
      significantly lower in sgk3(-/-) DCs than in sgk3(+/+) DCs, whereas Orai1, Orai2,
      STIM1 and TRPC1 transcript levels and/or protein abundance were similar in sgk3-/
      and sgk3(+/+) DCs. Migration of both, immature DCs towards CXCL12 and LPS
      matured DCs towards CCL21 was reduced in sgk3(-/-) as compared to sgk3(+/+) DCs.
      Migration of sgk3(+/+) DCs was further sensitive to SOC channel inhibitor 2-APB
      (50 uM) and to STIM1/STIM2 knock-down. CONCLUSION: SGK3 contributes to the
      regulation of store-operated Ca(2+) entry into and migration of dendritic cells,
      effects at least partially mediated through SGK3-dependent upregulation of STIM2
      expression.

PMID- 23171962
TI  - High electrochemical performance based on ultrathin porous CuO nanobelts grown on
      Cu substrate as integrated electrode.
AB  - A facile and low-cost approach has been developed to fabricate porous CuO
      nanobelts directly grown on a Cu substrate. The as-prepared CuO samples can be
      directly used as integrated electrodes for lithium-ion batteries and pseudo
      supercapacitors without the addition of other ancillary materials such as carbon
      black or a binder to enhance electrode conductivity and cycling stability. The
      unique nanostructural features endow them with excellent electrochemical
      performance as demonstrated by high capacities of 640 mA h g(-1) after 100 cycles
      at 0.2 C rate and an excellent specific capacitance of 340 F g(-1), which
      corresponds to the energy density of 45 W h kg(-1). The cyclability of the
      electrode demonstrates only a 10-15% loss in capacitance over 5000 cycles.

PMID- 23171971
TI  - Performance of statistical methods for meta-analysis when true study effects are
      non-normally distributed: a comparison between DerSimonian-Laird and restricted
      maximum likelihood.

PMID- 23171972
TI  - Although we appreciate the authors' efforts in conducting their comparative
      study, we disagree with some of the conclusions drawn.

PMID- 23171973
TI  - A similar DAG could be drawn for adherence-related issues.

PMID- 23171980
TI  - Tolerability and efficacy of newly developed penile injection of cross-linked
      dextran and polymethylmethacrylate mixture on penile enhancement: 6 months follow
      up.
AB  - Cross-linked dextran and polymethylmethacrylate mixture (Lipen-10) is newly
      developed tissue filler. The purpose of this study was to evaluate tolerability
      and efficacy of Lipen-10 on penile enhancement. Twenty adult males were included
      in this study. Lipen-10 was injected into the subcutaneous tissue of the penile
      shaft. The penile girth and length were measured in the flaccid state, before and
      1, 3 and 6 months after the injection. The circumference increased by 3.7+/-1.2
      cm (50.8%, P<0.0001) at penile base, 4.2+/-0.9 cm (59.0%, P<0.001) at mid-shaft,
      and 3.8+/-1.0 cm (53.2%, P<0.0001) at distal shaft and the length increased by
      2.3+/-1.4 cm (63.2%, P<0.001). There was, however, no significant difference
      between 3 and 6 months post-treatment in girth and length (P-values: 0.796,
      0.498, 0.600 and 0.084 for penile base, mid- and distal-shaft and length,
      respectively). The complications were only one mild asymmetry of penile shape and
      one 5-mm-sized nodule in the injected site. There were no clinically significant
      adverse events in all subjects. Penile injection of Lipen-10 led to a significant
      increase in penile size, showed a good durability and was well-tolerated, without
      serious adverse events. These results suggest that penile injection of Lipen-10
      may be a new effective method for penile enhancement.

PMID- 23171981
TI  - Hydrogen sulfide promotes nitric oxide production in corpus cavernosum by
      enhancing expression of endothelial nitric oxide synthase.
AB  - Recently, hydrogen sulfide (H2S) has been identified as a potential therapy for
      ED. However, a thorough understanding of its molecular mechanisms of action would
      be essential to develop H2S as a new therapy for ED. In this study, the effect of
      H2S on nitric oxide (NO) production, especially through the expression of
      constitutive nitric oxide synthase (NOS) isoforms-endothelial NOS (eNOS) and
      neuronal NOS (nNOS) in rat corpus cavernosum (CC) were explored. Real-time PCR
      studies subsequent to in vitro treatment of sodium hydrosulfide hydrate (NaHS), a
      stable H2S donor, showed increases in eNOS but not nNOS mRNA. Western blot
      studies confirmed that the exogenously applied NaHS increased eNOS but not nNOS
      protein expression in the rat CC. Furthermore, NaHS did not alter the expressed
      amounts of Caveolin-1 (CAV-1), a dominant inhibitory interaction partner of eNOS,
      in these tissues. Not surprisingly, NaHS also enhanced the NO production in eNOS
      associated membrane fraction of rat CC. Taken together, we ascertain that H2S
      could exert its proerectile effects by augmenting NO pathway. It appears that H2S
      would be particularly useful in improving the clinical outcome of ED patients,
      whose erectile impairment is due to an inherent attenuation of the endothelial NO
      formation in the cavernosum.

PMID- 23171985
TI  - P(VDF-TrFE) ferroelectric nanotube array for high energy density capacitor
      applications.
AB  - Poly(vinylidene-fluoride-co-trifluoroethylene) (P(VDF-TrFE)) ferroelectric
      nanotube arrays were fabricated using an anodized alumina membrane (AAM) as a
      template and silver electrodes were deposited on both the outer and inner sides
      of the nanotubes by an electroless plating method. The nanotubes have the unique
      structure of being sealed at one end and linked at the open end, thus preventing
      electrical shorting between the inner and outer electrodes. Compared with a P(VDF
      TrFE) film with a similar overall thickness, the idealized nanotube array has a
      theoretical capacitance that is 763 times larger due to the greatly enlarged
      contact area between the electrodes and the polymer dielectric. A capacitance
      that is 95 times larger has been demonstrated experimentally, thus indicating
      that such nanotube arrays are promising for realizing high density capacitance
      and high power dielectric energy storage.

PMID- 23171982
TI  - Basal bodies exhibit polarized positioning in zebrafish cone photoreceptors.
AB  - The asymmetric positioning of basal bodies, and therefore cilia, is often
      critical for proper cilia function. This planar polarity is critical for motile
      cilia function but has not been extensively investigated for nonmotile cilia or
      for sensory cilia such as vertebrate photoreceptors. Zebrafish photoreceptors
      form an organized mosaic ideal for investigating cilia positioning. We report
      that, in the adult retina, the basal bodies of red-, green-, and blue-sensitive
      cone photoreceptors localized asymmetrically on the cell edge nearest the optic
      nerve. In contrast, no patterning was seen in the basal bodies of ultraviolet
      sensitive cones or in rod photoreceptors. The asymmetric localization of basal
      bodies was consistent in all regions of the adult retina. Basal body patterning
      was unaffected in the cones of the XOPS-mCFP transgenic line, which lacks rod
      photoreceptors. Finally, the adult pattern was not seen in 7-days
      postfertilization (dpf) larvae; basal bodies were randomly distributed in all the
      photoreceptor subtypes. These results establish the asymmetrical localization of
      basal bodies in red-, green-, and blue-sensitive cones in adult zebrafish retinas
      but not in larvae. This pattern suggests an active cellular mechanism regulated
      the positioning of basal bodies after the transition to the adult mosaic and that
      rods do not seem to be necessary for the patterning of cone basal bodies.

PMID- 23171986
TI  - Improving diagnosis of primary cytomegalovirus infection in pregnant women using
      immunoblots.
AB  - Human cytomegalovirus (CMV) is the most common infectious cause of mental
      disability in newborns of developed countries. Transmission of CMV from mother to
      baby is more frequent in maternal primary infection, although CMV reactivation
      causes more congenital infections overall. Current diagnostic tests for
      distinguishing primary and reactivation CMV have problems with interpretation and
      immunoblots may assist with diagnosis. Sera from 60 pregnant women were analyzed
      using conventional serology in parallel with a commercial immunoblot assay (using
      Recomblot, Mikrogen Diagnostik). Comparison of detection of CMV IgG, IgM, IgG
      avidity in maternal primary infection showed the immunoblot relative to
      conventional serology had sensitivity and specificity of 100% for IgG
      identification. The detection of IgM on immunoblot showed sensitivity of 75%,
      specificity of 62.5%, positive predictive value (PPV) of 81.8% and negative
      predictive value (NPV) of 52.6%. The immunoblot IgG avidity assay had sensitivity
      of 94.1%, with a PPV of 100% when identifying low avidity serum samples, and
      sensitivity of 100% with a PPV of 97.1% for high avidity serum samples. Overall
      agreement between conventional serology (IgM, IgG avidity) and immunoblot (IgM,
      IgG avidity) for detection of primary CMV infection was 65%. Although the
      immunoblot is effective in detecting IgG and determining IgG avidity, it showed
      no significant benefits in performance or utility as a first line diagnostic
      technique for IgM or primary CMV infection in pregnant women.

PMID- 23171987
TI  - [Evaluation of 10 years experience with endo-exo femur prostheses - background,
      data and results].
AB  - Between 1999 and 2011 the Endo-Exo femur prosthesis has been applied to 54
      patients. This comparatively new method for patient rehabilitation after upper
      leg amputation includes a two-step surgical procedure. The first step is an
      operation where the endomodule of the stem prosthesis is implanted in the bone
      via a press-fit technique. Then the soft tissue coat is closed to give the bone
      enough time for a secure osseointegration of the prosthesis. About six weeks
      later a stoma is cut out and the adapter for the exo-part is connected. The
      prosthesis is therefore intramedullary anchored and percutaneously penetrating
      the skin. A critical examination of this procedure has to put its main attention
      to the latent danger of an ascending, intramedullary infection. This may arise
      from the skin-penetrating stoma region at the distal stump. All data derived from
      patients operated in Lubeck, Germany have been evaluated focusing on reasons for
      objectionable operative procedures and their resulting terms of treatment. The
      evaluation shows that the initially high rate of stoma-associated infections of
      the soft tissue coat could be dramatically reduced through a change of design of
      the skin-penetrating parts. In between January 2009 and December 2011 (altogether
      24 implants/23 patients) no operative revisions had to be undertaken because of
      infections of the stoma. Next to this there are more characteristics
      conditionally caused by the implant - like fractures of the affected extremity
      and other complications - presented in terms of cause-related case histories.

PMID- 23171989
TI  - Development of fluorous porous polymer monolith (FPPM) for the capillary
      electrochromatographic separation of fluorous analytes based on fluorous-fluorous
      interaction.
AB  - This is the first report on the CEC separation of fluorous analytes on a fluorous
      porous polymer monolith (FPPM) stationary phase based on fluorous-fluorous
      interaction. Monolithic columns do not require retaining frits and can be
      conveniently photo-patterned within a capillary. Two groups of fluorous
      compounds, a N-f-Cbz-4-nitro-benzylamine (N) series and a N-f-Cbz-4-phenyl
      benzylamine (P) series, each series having compounds differing only by the length
      of their perfluorinated tag, were employed to evaluate the ability of the
      fluorinated column to separate fluorous analytes using a variety of mobile phase
      compositions and separation conditions. Fluorous monoliths showed enhanced
      separation performance by providing better selectivity, higher resolution and
      shorter analysis time compared to a similar non-fluorous (reversed phase)
      monolithic column. Under optimal conditions, column efficiency as high as 234,000
      plates per metre was achieved, and all four compounds of the N series were fully
      resolved in <5 minutes. Perfluoromethylene selectivity was used to quantitatively
      evaluate the interaction between the perfluorinated chain on the analytes and
      both the FPPM and non-FPPM columns. It was found that the non-FPPM column
      resolves fluorous analytes mainly based on reversed phase interaction while the
      FPPM column resolves them mainly based on fluorous-fluorous interaction. Results
      are compared to fluorous monolith columns used in a nano-liquid-chromatographic
      (nano-LC) separation with gradient elution. The FPPM column required less than
      one fifth the analysis time in CEC mode than was required in nanoLC mode, with
      superior separation efficiency and resolution. FPPM stationary phases provide an
      attractive option for the analysis of perfluorinated analytes, which is expected
      to be useful in areas such as proteomics for the separation of fluorously tagged
      proteins, and in environmental analysis where fluorinated species are of
      increasing concern.

PMID- 23171988
TI  - [Malpractice in the treatment of diaphyseal fractures in children - experience of
      the Arbitration Office of the Northern German Medical Boards].
AB  - BACKGROUND: Statistics of the Arbitration Office of the North German Medical
      Boards for extrajudicial claim resolution show that nearly 30 % of all panel
      proceedings confirm medical malpractice. In proceedings concerning fractures in
      children the percentage rises to 63 % with significant differences in various
      fracture localisations. METHODS: Between 2000 and 2011 the Arbitration Office
      dealt with 272 panel proceedings regarding the fracture treatment in children. In
      this study 83 proceedings concerning the treatment of diaphyseal fractures of the
      long bones are evaluated. RESULTS: The claims were related to the following
      specialities (p = number of proceedings, m = number of malpractices):
      orthopaedics/traumatology p = 46, m = 38; general surgery p = 17, m = 21;
      paediatric surgery p = 16, m = 13; anaesthesia p = 1, m = 1; general practitioner
      p = 2, m = 2. In 7 cases concerning obstetrics (4) and paediatrics (3) no
      malpractices could be established. In 5 cases two facilities/doctors were
      included in the same proceeding. On 17 occasions, 2 errors were made that were
      unrelated to each other. The overall frequency of malpractice was 69 % with no
      significant differences between the involved facilities. The diaphyseal fracture
      locations were: humerus p = 5, m = 2; radius and/or ulna (Monteggia fractures
      excluded): p = 29, m = 20; femur p = 29, m = 20; tibia (with or without fracture
      of the fibula): p = 20, m = 14. In conservative fracture treatment the following
      negligent adverse events were confirmed: severe skin lesions owing to either
      plaster extension or removal of the cast (11), omitted or insufficient reduction
      followed by consolidation in intolerable malposition (8), no inducement of
      corrective measures after consolidation in intolerable displacement (11).
      Following malpractices in the surgical treatment were classified as: no
      indication for surgical treatment (2), no osteosynthesis in spite of clear
      indication (3), technical failures in primary osteosynthesis (16), technical
      failures in repeated osteosynthesis (4), aspiration pneumonia due to missed
      intubation (1). The applied methods of osteosynthesis were intramedullary
      nailing, mainly ESIN p = 24, m = 12; plate p = 24, m = 5; fixateur externe p = 7,
      m = 5. The results of maltreated diaphyseal fractures were altogether moderate:
      transitional impairment due to delayed or repeated therapeutic measures with
      prolonged fracture healing, no functional loss 70 %, slight deformation of the
      forearm, minimal loss of mobility 21 %, remarkable deformation of the forearm
      with considerable impairment of mobility, especially pronation/supination,
      deformation of the radio-ulno-carpal joint unit 7 %. DISCUSSION: There are three
      main categories in the maltreatment of diaphyseal fractures: 1) Omission of
      fracture reduction with or without internal stabilisation in cases of relevant
      axial deviation by unjustified expectation of "spontaneous correction". 2)
      Omission of fracture reduction in cases of unmotivated or neglected secondary
      displacement. 3) Technical failures in performing of osteosynthesis resulting in
      instability or the creation of intolerable malposition requiring re
      osteosynthesis. The high number of plate osteosyntheses in our series (44 %) is
      not representative for the general treatment of children's fractures in Germany.
      Most cases of plate osteosynthesis are related to corrective measures with clear
      indication. In nine casuistic representations the errors in treatment are
      explained. CONCLUSION: The evaluation of malpractice in the treatment of
      diaphyseal fractures in children confirms the consensus: correct assessment of
      fracture type, early adequate treatment and fracture control, early corrective
      measures after insufficient primary reduction or secondary dislocation, lead to
      fracture healing without any anatomic or functional deficiency. Reverse argument:
      fracture healing leading to anatomic and/or functional loss gives a very probable
      indication of malpractice.

PMID- 23171990
TI  - En-bloc femoral cement removal after failure of cemented total hip replacement in
      two dogs.
AB  - In two dogs with periprosthetic infection after total hip replacement, the
      femoral cement mantle was retrieved by proximal extraction without an invasive
      osteotomy or cortical fenestration. En-bloc femoral cement removal was performed
      by injection of polymethylmethacrylate cement into the central mantle void left
      after stem removal, and by threading a positive profile pin into the newly
      injected cement. Once the PMMA had polymerized, the pin was withdrawn with the
      entire mantle attached. This technique should be considered in patients with
      circumferential deterioration of the femoral bone-cement interface in which the
      diameter of the femoral isthmus would not obstruct withdrawal of the cement
      mantle.

PMID- 23171993
TI  - Enhanced charge transportation in a polypyrrole counter electrode via
      incorporation of reduced graphene oxide sheets for dye-sensitized solar cells.
AB  - In this work, reduced graphene oxide (RGO) sheets are successfully introduced
      into the conductive polypyrrole (PPy) matrix as conductive channels and co
      catalyst, through simple incorporation of graphene oxide (GO) into PPy and
      subsequent in situ reduction from GO/PPy to RGO/PPy composite film. The RGO/PPy
      film is fabricated as a counter electrode for dye-sensitized solar cells, and it
      exhibits excellent catalytic performance for reduction of triiodide. For this
      reason, the incorporated RGO sheets significantly improve short-circuit
      photocurrent density from 14.27 to 15.81 mA cm(-2) and power conversion
      efficiency from 7.11% to 8.14%, which is comparable with that for the cell based
      on a Pt cathode.

PMID- 23171995
TI  - Alternating syndrome of inappropriate secretion of antidiuretic hormone and
      cerebral salt wasting in an infant with brain tumor.

PMID- 23171994
TI  - Microdialysis in early detection of temporary pancreatic ischemia in a porcine
      model.
AB  - BACKGROUND: Ischemic injury to the pancreas occurs in various clinical
      conditions. A method for online monitoring of pathophysiological events in
      pancreatic parenchyma is missing. AIMS: To assess the timing of microdialysis
      (MD) technique response on temporary changes in pancreatic perfusion, and to
      evaluate the relationship between MD data and systemic markers of anaerobic
      metabolism and inflammation. METHODS: In anaesthetized normoventilated pigs, MD
      probes were placed in right (control) and left (ischemic) pancreatic lobes,
      respectively. Following the clamping of the vessels, ischemia was verified by
      tissue oxygen tension (P(ti)O(2)) measurements. RESULTS: P(ti)O(2) decreased
      within 20 min after the clamping of the vessels, already returning to baseline
      levels at the first sampling point after the removal of the clamp. MD lactate
      levels increased, whereas pyruvate and glucose levels decreased at 20 min after
      the induction of ischemia. These trends continued until the end of ischemia and
      returned to baseline following reperfusion. Serum lactate, amylase and tumor
      necrosis factor-alpha levels decreased throughout the protocol time. CONCLUSION:
      MD data were in concordance with changes in P(ti)O(2), which is indicative of
      local anaerobic metabolism. MD allowed the detection of pathophysiological
      processes within the ischemic pancreas at a stage when no elevations of systemic
      markers of ischemia or inflammation were observed.

PMID- 23171996
TI  - Neutrophils engraftment delay during tigecycline treatment in 2 bone marrow
      transplanted patients.
AB  - BACKGROUND: Tigecycline is the first available drug of glycylcycline family.
      Because of recent introduction, some of its adverse effects could be still
      unexplored. OBSERVATION: We report the cases of 2 boys who underwent an allogenic
      bone marrow transplantation for acute myeloid leukemia and were treated with
      tigecycline. Erythrocyte and platelet engraftment followed a normal course, but
      the neutrophil count remained low despite the increase in leukocyte count. After
      tigecycline interruption, the neutrophil count rapidly raised in both cases.
      CONCLUSIONS: Neutropenia was suspected to be secondary to tigecycline exposure.
      In vitro experiments were performed, which suggested tigecycline influence on
      myeloid cells survival.

PMID- 23171997
TI  - Genotype instability during long-term subculture of lymphoblastoid cell lines.
AB  - Epstein-Barr virus (EBV)-transformed lymphoblastoid cell lines (LCLs) promise to
      address the challenge posed by the limited availability of primary cells needed
      as a source of genomic DNA for genetic studies. However, the genetic stability of
      LCLs following prolonged culture has never been rigorously investigated. To
      evaluate genotypic errors caused by EBV integration into human chromosomes, we
      isolated genomic DNA from human peripheral blood mononuclear cells and LCLs
      collected from 20 individuals and genotyped the DNA samples using the Affymetrix
      500K SNP array set. Genotype concordance measurements between two sources of DNA
      from the same individual indicated that genotypic discordance is negligible in
      early-passage LCLs (<20 passages) but substantial in late-passage LCLs (>50
      passages). Analysis of concordance on a chromosome-by-chromosome basis identified
      genomic regions with a high frequency of genotypic errors resulting from the loss
      of heterozygosity observed in late-passage LCLs. Our findings suggest that,
      although LCLs harvested during early stages of propagation are a reliable source
      of genomic DNA for genetic studies, investigations that involve genotyping of the
      entire genome should not use DNA from late-passage LCLs.

PMID- 23171999
TI  - Controlled beta-protonation and [4+2] cycloaddition of enals and chalcones via N
      heterocyclic carbene/acid catalysis: toward substrate independent reaction
      control.
AB  - A substrate-independent selective generation of enolates over homoenolate
      equivalents in NHC-catalyzed reactions of enals and chalcones is disclosed. Acid
      co-catalysts play vital roles in control of the reaction pathways, allowing for
      individual access to diverse products from identical substrates.

PMID- 23171998
TI  - Constructing a contemporary gene-environmental cohort: study design of the
      Yamagata Molecular Epidemiological Cohort Study.

PMID- 23172000
TI  - Modeling schizophrenia using induced pluripotent stem cell-derived and fibroblast
      induced neurons.
AB  - Although schizophrenia affects a number of brain regions and produces a range of
      clinical symptoms, we believe its origins lie at the level of single neurons and
      simple networks. Owing to this, as well as to its high degree of heritability, we
      hypothesize that schizophrenia is amenable to cell-based studies in vitro. Using
      induced pluripotent stem cell-derived neurons and/or fibroblast-induced neurons,
      a limitless quantity of live human neurons can now be generated from patient skin
      biopsies. We predict that cell-based studies will ultimately contribute to our
      understanding of the molecular and cellular underpinnings of this debilitating
      disorder.

PMID- 23172001
TI  - A randomized controlled trial of bibliotherapy for carers of young people with
      first-episode psychosis.
AB  - Caring for young people with first-episode psychosis (FEP) is challenging and can
      adversely affect carer well-being, with limited evidence-based support materials
      available. We aimed to examine whether completion of a self-directed problem
      solving bibliotherapy among carers of young people with FEP led to a better
      experience of caring, less distress and expressed emotion, and better general
      health than carers who only received treatment as usual (TAU). A randomized
      controlled trial was conducted across two early-intervention psychosis services
      in Melbourne, Australia. A total of 124 carers were randomized to problem-solving
      bibliotherapy intervention (PSBI) or TAU and assessed at baseline, 6-week and 16
      week follow-up. Intent-to-treat analyses were carried out and indicated that
      recipients of PSBI had a more favorable experience of caring than those receiving
      TAU, and these effects were sustained at both follow-up time points. Across the
      other measures, both groups demonstrated improvements by week 16, although the
      PBSI group tended to improve earlier. The PSBI group experienced a greater
      reduction in negative emotional evaluations of the need to provide additional
      support to young people with FEP than the TAU group by week 6, while the level of
      psychological distress decreased at a greater rate from baseline to 6 weeks in
      the PSBI compared with the TAU group. These findings support the use of problem
      solving bibliotherapy for first-time carers, particularly as a cost-effective
      adjunct to TAU. 

PMID- 23172003
TI  - A systematic review and meta-analysis of recovery in schizophrenia.
AB  - OBJECTIVE: Our primary aims were (a) to identify the proportion of individuals
      with schizophrenia and related psychoses who met recovery criteria based on both
      clinical and social domains and (b) to examine if recovery was associated with
      factors such as gender, economic index of sites, and selected design features of
      the study. We also examined if the proportions who met our definition of recovery
      had changed over time. METHOD: A comprehensive search strategy was used to
      identify potential studies, and data were extracted for those that met inclusion
      criteria. The proportion who met our recovery criteria (improvements in both
      clinical and social domains and evidence that improvements in at least 1 of these
      2 domains had persisted for at least 2 years) was extracted from each study. Meta
      regression techniques were used to explore the association between the recovery
      proportions and the selected variables. RESULTS: We identified 50 studies with
      data suitable for inclusion. The median proportion (25%-75% quantiles) who met
      our recovery criteria was 13.5% (8.1%-20.0%). Studies from sites in countries
      with poorer economic status had higher recovery proportions. However, there were
      no statistically significant differences when the estimates were stratified
      according to sex, midpoint of intake period, strictness of the diagnostic
      criteria, duration of follow-up, or other design features. CONCLUSIONS: Based on
      the best available data, approximately, 1 in 7 individuals with schizophrenia met
      our criteria for recovery. Despite major changes in treatment options in recent
      decades, the proportion of recovered cases has not increased.

PMID- 23172002
TI  - The myth of schizophrenia as a progressive brain disease.
AB  - Schizophrenia has historically been considered to be a deteriorating disease, a
      view reinforced by recent MRI findings of progressive brain tissue loss over the
      early years of illness. On the other hand, the notion that recovery from
      schizophrenia is possible is increasingly embraced by consumer and family groups.
      This review critically examines the evidence from longitudinal studies of (1)
      clinical outcomes, (2) MRI brain volumes, and (3) cognitive functioning. First,
      the evidence shows that although approximately 25% of people with schizophrenia
      have a poor long-term outcome, few of these show the incremental loss of function
      that is characteristic of neurodegenerative illnesses. Second, MRI studies
      demonstrate subtle developmental abnormalities at first onset of psychosis and
      then further decreases in brain tissue volumes; however, these latter decreases
      are explicable by the effects of antipsychotic medication, substance abuse, and
      other secondary factors. Third, while patients do show cognitive deficits
      compared with controls, cognitive functioning does not appear to deteriorate over
      time. The majority of people with schizophrenia have the potential to achieve
      long-term remission and functional recovery. The fact that some experience
      deterioration in functioning over time may reflect poor access, or adherence, to
      treatment, the effects of concurrent conditions, and social and financial
      impoverishment. Mental health professionals need to join with patients and their
      families in understanding that schizophrenia is not a malignant disease that
      inevitably deteriorates over time but rather one from which most people can
      achieve a substantial degree of recovery. 

PMID- 23172004
TI  - Diagnosis and management of superior labral anterior posterior tears in throwing
      athletes.
AB  - Injury to the superior glenoid labrum is increasingly recognized as a significant
      source of shoulder pain and dysfunction in the throwing athlete. Several theories
      have been proposed to explain the pathogenesis of superior labral anterior
      posterior (SLAP) tears. The clinical examination of the superior labrum-biceps
      tendon complex remains challenging because of a high association of other
      shoulder injuries in overhead athletes. Many physical examination findings have
      high sensitivity and low specificity. Advances in soft tissue imaging such as
      magnetic resonance arthrography allow for improved detection of labrum and biceps
      tendon lesions, although correlation with history and physical examination is
      critical to identify symptomatic lesions. Proper treatment of throwers with SLAP
      tears requires a thorough understanding of the altered biomechanics and the
      indications for nonoperative management and arthroscopic treatment of these
      lesions.

PMID- 23172005
TI  - Direct FGF-2 gene transfer via recombinant adeno-associated virus vectors
      stimulates cell proliferation, collagen production, and the repair of
      experimental lesions in the human ACL.
AB  - BACKGROUND: Basic fibroblast growth factor (FGF-2) is a powerful stimulator of
      fibroblast proliferation and type I/III collagen production. HYPOTHESIS:
      Overexpression of FGF-2 via direct recombinant adeno-associated virus (rAAV)
      vector-mediated gene transfer enhances the healing of experimental lesions to the
      human anterior cruciate ligament (ACL). STUDY DESIGN: Controlled laboratory
      study. METHODS: rAAV vectors carrying a human FGF-2 sequence or the lacZ marker
      gene were applied to primary human ACL fibroblasts in vitro and to intact or
      experimentally injured human ACL explants in situ to evaluate the efficacy and
      duration of transgene expression and the potential effects of FGF-2 treatment
      upon the proliferative, metabolic, and regenerative activities in these systems.
      RESULTS: Sustained, effective dose-dependent lacZ expression was achieved in all
      systems tested (up to 96% +/- 2% in vitro and 80%-85% in situ for at least 30
      days). rAAV allowed for continuous FGF-2 production both in vitro and in the
      intact ACL in situ (32.7 +/- 1.4 and 33.1 +/- 0.8 pg/mL/24 h, respectively, ie,
      up to 41-fold more than in the controls at day 30; always P <= .001), leading to
      significantly and durably enhanced levels of proliferation and type I/III
      collagen production vis-a-vis lacZ (at least 3- and 4-fold increases at day 30,
      respectively; always P <= .001). Most notably, rAAV FGF-2 promoted a significant,
      long-term production of the factor in experimental ACL lesions (92.7 +/- 3.9
      pg/mL/24 h, ie, about 5-fold more than in the controls; P <= .001) associated
      with enhanced levels of proliferation and type I/III collagen synthesis (at least
      2- and 4-fold increases at day 30, respectively; always P <= .001). Remarkably,
      the FGF-2 treatment allowed for a decrease in the amplitude of such lesions
      possibly because of the increased expression in contractile alpha-smooth muscle
      actin, ligament-specific transcription factor scleraxis, and nuclear factor
      kappaB for proliferation and collagen deposition, which are all markers commonly
      induced in response to injury. CONCLUSION: Efficient, stable FGF-2 expression via
      rAAV enhances the healing of experimental human ACL lesions by activating key
      cellular and metabolic processes. CLINICAL RELEVANCE: This approach has potential
      value for the development of novel, effective treatments for ligament
      reconstruction.

PMID- 23172006
TI  - Correlation between endobutton loop length and tunnel widening after hamstring
      anterior cruciate ligament reconstruction.
AB  - BACKGROUND: Previous reports have shown that graft fixation with the Endobutton
      is associated with tunnel widening because it provides distant fixation rather
      than aperture fixation. HYPOTHESIS: A longer loop of the Endobutton results in
      greater tunnel widening than a shorter loop. STUDY DESIGN: Cohort study; Level of
      evidence, 3. METHODS: A total of 171 consecutive patients underwent hamstring
      anterior cruciate ligament (ACL) reconstruction fixed with the Endobutton. They
      were followed for a minimum of 2 years postoperatively. A 15-mm loop was used in
      20 patients, a 20-mm loop in 53, a 25-mm loop in 58, and a >30-mm loop in 40. On
      anterior-posterior (AP) and lateral radiographs, the measured diameters of the
      femoral tunnel at 2 years after surgery were compared with the diameter of the
      reamer used at surgery. The measured diameter of the tibial tunnel at 2 years
      after surgery was compared with measurements taken on the immediate postoperative
      day. The center of the tibial tunnel and direction of the ACL graft were also
      measured. Postoperative knee stability was evaluated using the Lachman test,
      pivot-shift test, and KT-1000 arthrometer. Functional evaluations were performed
      using the Lysholm score and Tegner activity scale. All measurements were compared
      among the 4 groups according to the length of the Endobutton loop. RESULTS: The
      mean +/- standard deviation (SD) diameter of the femoral tunnel increased by
      50.7% +/- 23.3% and 37.0% +/- 18.8% on AP and lateral radiographs at 2 years
      after surgery, respectively. The mean +/- SD diameter of the tibial tunnel
      increased by 40.8% +/- 19.3% and 46.4% +/- 22.6% on AP and lateral radiographs,
      respectively. No significant difference in tunnel widening was present according
      to the length of the Endobutton loop. There were no significant differences in
      the average center of the tibial tunnel or the average angle of the direction of
      the ACL graft among the 4 groups. There was no significant difference in Lachman
      test results, postoperative KT-1000 arthrometer side-to-side differences, Lysholm
      score, and Tegner activity scale score among the 4 groups. The group with a >30
      mm loop showed a significant difference in the pivot-shift test than the other 3
      groups (P = .023). CONCLUSION: A longer Endobutton loop did not result in greater
      tunnel widening than a shorter loop. Long fixation distance may not be associated
      with tunnel widening after hamstring ACL reconstructions.

PMID- 23172007
TI  - Three-dimensional evaluation of cyclic displacement in single-row and double-row
      rotator cuff reconstructions under static external rotation.
AB  - BACKGROUND: The double-row suture bridge repair was recently introduced and has
      demonstrated superior biomechanical results and higher yield load compared with
      the traditional double-row technique. It therefore seemed reasonable to compare
      this second generation of double-row constructs to the modified single-row double
      mattress reconstruction. HYPOTHESIS: The repair technique, initial tear size, and
      tendon subregion will have a significant effect on 3-dimensional (3D) cyclic
      displacement under additional static external rotation of a modified single-row
      compared with a double-row rotator cuff repair. STUDY DESIGN: Controlled
      laboratory study. METHODS: Rotator cuff tears (small to medium: 25 mm; medium to
      large: 35 mm) were created in 24 human cadaveric shoulders. Rotator cuff repairs
      were performed as modified single-row or double-row repairs, and cyclic loading
      (10-60 N, 10-100 N) was applied under 20 degrees  of external rotation.
      Radiostereometric analysis was used to calculate cyclic displacement in the
      anteroposterior (x), craniocaudal (y), and mediolateral (z) planes with a focus
      on the repair constructs and the initial tear size. Moreover, differences in
      cyclic displacement of the anterior compared with the posterior tendon subregions
      were calculated. RESULTS: Significantly lower cyclic displacement was seen in
      small to medium tears for the single-row compared with double-row repair at 60
      and 100 N in the x plane (P = .001) and y plane (P = .001). The results were
      similar in medium to large tears at 100 N in the x plane (P = .004). Comparison
      of 25-mm versus 35-mm tears did not show any statistically significant
      differences for the single-row repairs. In the double-row repairs, lower gap
      formation was found for the 35-mm tears (P <= .05). Comparison of the anterior
      versus posterior tendon subregions revealed a trend toward higher anterior gap
      formation, although this was statistically not significant. CONCLUSION: The
      tested single-row reconstruction achieved superior results in 3D cyclic
      displacement to the tested double-row repair. Extension of the initial rupture
      size did not have a negative effect on the biomechanical results of the tested
      constructs. CLINICAL RELEVANCE: Single-row repairs with modified suture
      configurations provide comparable biomechanical strength to double-row repairs.
      Furthermore, as increased gap formation in the early postoperative period might
      lead to failure of the construct, a strong anterior fixation and restricted
      external rotation protocol might be considered in rotator cuff repairs to avoid
      this problem.

PMID- 23172008
TI  - Effects of bandwidth, compression speed, and gain at high frequencies on
      preferences for amplified music.
AB  - This article reviews a series of studies on the factors influencing sound quality
      preferences, mostly for jazz and classical music stimuli. The data were obtained
      using ratings of individual stimuli or using the method of paired comparisons.
      For normal-hearing participants, the highest ratings of sound quality were
      obtained when the reproduction bandwidth was wide (55 to 16000 Hz) and ripples in
      the frequency response were small (less than +/- 5 dB). For hearing-impaired
      participants listening via a simulated five-channel compression hearing aid with
      gains set using the CAM2 fitting method, preferences for upper cutoff frequency
      varied across participants: Some preferred a 7.5- or 10-kHz upper cutoff
      frequency over a 5-kHz cutoff frequency, and some showed the opposite preference.
      Preferences for a higher upper cutoff frequency were associated with a shallow
      high-frequency slope of the audiogram. A subsequent study comparing the CAM2 and
      NAL-NL2 fitting methods, with gains slightly reduced for participants who were
      not experienced hearing aid users, showed a consistent preference for CAM2. Since
      the two methods differ mainly in the gain applied for frequencies above 4 kHz
      (CAM2 recommending higher gain than NAL-NL2), these results suggest that
      extending the upper cutoff frequency is beneficial. A system for reducing
      "overshoot" effects produced by compression gave small but significant benefits
      for sound quality of a percussion instrument (xylophone). For a high-input level
      (80 dB SPL), slow compression was preferred over fast compression.

PMID- 23172009
TI  - Musical sound quality impairments in cochlear implant (CI) users as a function of
      limited high-frequency perception.
AB  - The purpose of this study was to (a) apply the musical sound quality assessment
      method, Cochlear Implant-MUltiple Stimulus with Hidden Reference and Anchor (CI
      MUSHRA), to quantify musical sound quality deficits in CI (cochlear implant)
      users with respect to high-frequency loss, and (b) assess possible correlations
      between CI-MUSHRA performance and self-reported musical sound quality, as
      assessed by more traditional rating scales. Five versions of real-world musical
      stimuli were created: 8-,4-, and 2-kHz low-pass-filtered (LPF) versions with
      increasing high-frequency removal, a composite stimulus containing a 1-kHz LPF
      filtered version and white noise ("anchor"), and an unaltered version ("hidden
      reference"). Using the CI-MUSHRA methodology, these versions were simultaneously
      presented to participants in addition to a labeled reference. Participants
      listened to all versions and provided ratings based on a 100-point scale that
      reflected perceived sound quality difference among the versions. A total of 25
      musical stimuli were tested. As comparison measures, participants completed four
      Visual Analogue Scales (VAS) to assess musical sound quality. Overall, compared
      to normal hearing (NH) listeners, CI users demonstrated an impaired ability to
      discriminate between unaltered and altered musical stimuli with variable amounts
      of high-frequency information removed. Performance using CI-MUSHRA to evaluate
      this parameter did not correlate to measurements of musical sound quality, as
      assessed by VAS. This study identified high-frequency loss as one acoustic
      parameter contributing to overall CI-mediated musical sound quality limitations.
      CI-MUSHRA provided a quantitative assessment of musical sound quality. This
      method offers the potential to quantify CI impairments of many different acoustic
      parameters related to musical sound quality in the future.

PMID- 23172010
TI  - Catalytic enantioselective [4 + 2]-cycloaddition: a strategy to access aza
      hexacycles.
AB  - The aza-Diels Alder reaction has become one of the most widely used synthetic
      tools for the preparation of N-containing 6-membered heterocycles. Numerous
      important developments have been reported to render this reaction catalytic and
      enantioselective. This tutorial review highlights strategies and recent advances
      to achieve high efficiency and selectivity through the use of organocatalysts and
      transition metal complexes, allowing also the extension of this transformation
      substrate scope.

PMID- 23172011
TI  - Lessons learned while implementing mandatory health care-associated infection
      reporting in New York State.
AB  - New York State Public Health Law S2819, requiring the mandatory public reporting
      of health care-associated infections, was enacted in July 2005. This article
      describes key provisions in the legislation, New York State health care
      associated infection program development, the rationale for selection of the
      National Healthcare Safety Network for reporting, and lessons learned.

PMID- 23172014
TI  - Pig kidney transplantation: an up-to-date guideline.
AB  - BACKGROUND: Swine and human beings have many aspects in common that make swine a
      well-characterized large animal model for kidney transplantation (KTx). However,
      pigs have some peculiar anatomical characteristics that standardized techniques
      must adapt to. The aim of this study was to prepare an up-to-date guideline for
      porcine KTx. METHODS: To achieve this goal, we performed a Medline search using
      the terminology 'kidney' or 'renal' and 'transplantation' and 'pig' or 'swine' or
      'porcine'. We found over 1,300 published articles since 1963. Only 13 studies
      focused on the surgical aspect. Furthermore, we reviewed related books and
      articles about swine anatomical characteristics and surgery. Finally, our
      experimental experiences of KTx during the last few decades were added to this
      collection. RESULTS: Proper hosting, fasting, anesthesia, medical therapy and
      monitoring can prevent postoperative complications. Explantation with a Carrel
      patch of the aorta facilitates the implantation and prevents future stenosis.
      Native nephrectomy makes the follow-up of the implanted organ more precise. KTx
      in the infrarenal fossa via end-to-side anastomosis to the aorta and inferior
      vena cava followed by ureteroureterostomy are the recommended options for KTx in
      pigs compared to other possible methods. CONCLUSION: Pigs, with respect to their
      characterizations, constitute one of the best large animal models for KTx.
      Preoperative preparations are as important as the intra- and postoperative
      management. Using the most adaptable methods of surgery with respect to the
      specific anatomical characteristics of pigs can prevent undermining the studies
      and avoid preventable complications and pitfalls.

PMID- 23172015
TI  - A novel chromatographic peak alignment method coupled with trilinear
      decomposition for three dimensional chromatographic data analysis to obtain the
      second-order advantage.
AB  - The alignment of chromatographic peaks and deconvolution of overlapped peaks
      still remain challenges in the field of complex sample analysis. In this paper,
      we highlight a strategy that employs a new time shift alignment method derived
      from the well-known Rank Minimization method for aligning chromatographic peak
      shifts among samples and then uses trilinear decomposition methodology to
      interpret the overlapped chromatographic peaks in order to quantify analytes of
      interest. The performance of this novel strategy for chromatographic data
      analysis was evaluated using simulated chromatographic data as well as real
      chromatographic data. The results indicate that the new time shift alignment
      method can accurately correct time shifts in test samples even in the presence of
      unexpected interferences, and thus the low-rank trilinearity of the same analyte
      can be obtained, which will be helpful for trilinear decomposition to achieve the
      second-order advantage. Moreover, the results showed that this new alignment
      method is more automated in comparison with the Rank Minimization method and will
      be suitable for the alignment of the time shifts of analytes that are completely
      overlapped by coeluted interferences.

PMID- 23172016
TI  - Contrast magnetic resonance imaging for measurement of cartilage
      glycosaminoglycan content in dogs: a pilot study.
AB  - OBJECTIVE: To assess the ability of a contrast-enhanced magnetic resonance
      imaging (MRI) technique to quantitatively determine glycosaminoglycan content in
      canine articular cartilage. METHODS: Fifty-four full-thickness cartilage discs
      were collected from the femorotibial and scapulohumeral joints of three adult
      dogs immediately following euthanasia. One set of discs from each dog was
      analysed for glycosaminoglycan content using a colourimetric laboratory assay.
      The remaining position-matched set of discs from contralateral limbs underwent
      pre- and post-contrast gadolinium-enhanced MRI, using repeated saturation
      recovery pulse sequences which were used to generate calculated T1 maps of the
      cartilage discs. Linear regression analysis was then performed relating delayed
      gadolinium-enhanced MRI T1 calculated signal intensity to the cartilage
      glycosaminoglycan content normalized to DNA content. Repeatability of triplicate
      measurements was estimated by calculating the coefficient of variation. RESULTS:
      Mean coefficient of variation estimates for the gadolinium-enhanced MRI T1 signal
      intensity values for nine sampling sites from three dogs ranged from 5.9% to
      7.5%. Gadolinium-enhanced MRI T1 signal intensity was significantly correlated (p
      <0.05) with normalized glycosaminoglycan content in two dogs (r = 0.79, p =
      0.011; r = 0.78, p = 0.048), but not in the third dog (r = 0.53, p = 0.071).
      CLINICAL SIGNIFICANCE: Gadolinium-enhanced MRI assessment of cartilage may be
      predictive of glycosaminoglycan content and therefore offer an in vivo assessment
      of changes in cartilage characteristics over time. Additional studies appear
      indicated to determine the reliability and clinical applicability of gadolinium
      enhanced MRI in detecting changes in cartilage over time.

PMID- 23172020
TI  - [Invasive fungal infections in immunocompromised patients with focus on
      aspergillosis and its causative agents].
AB  - Invasive fungal diseases (IFD) are a life-threatening infectious complications in
      immunocompromised patients and are associated with high rate of morbidity and
      mortality. The most common invasive mycosis in patients who underwent an
      allogeneic hematopoietic stem cell transplantation is invasive aspergilosis (IA),
      most frequently caused by the clinically dominant species Aspergillus fumigatus
      and, rarely, also by Aspergillus flavus, Aspergillus terreus and Aspergillus
      niger. In recent years, other related Aspergillus species were also reported to
      cause IFD, phenotypically similar to A. fumigatus and moreover, frequently
      exhibiting resistance towards various antifungals. For example, it is Aspergillus
      lentulus, Aspergillus viridinutans, Neosartoya fischeri, etc.  Classical
      microbiological methods such as direct microscopy or culture are usually used for
      the identification of Aspergillus species. The application of PCR-based molecular
      techniques and monitoring of secondary metabolites production enable detection
      and identification of species, which are not distinguishable solely by their
      morphology. PCR methods are also useful for molecular strain typing of aspergilli
      and can reveal the genetic diversity of isolates.

PMID- 23172021
TI  - [Invasive mucormycosis in pediatric hematology patients--single-center experience
      from 2005-2010].
AB  - BACKGROUND: Mucormycosis is an invasive fungal disease severely complicating
      treatment of patients with hematologic diseases. Effective therapy is represented
      by the combination of surgery and amphotericin B administration and early
      initiation of the therapy is necessary for favorable outcome. The first clinical
      symptoms are usually non-specific and this can lead to late therapy onset. The
      objective of this retrospective work was to determine the frequency, risk factors
      and outcome of invasive mucormycosis in pediatric hematology patients. MATERIAL
      AND METHODS: The study cohort comprised 399 patients diagnosed with hematologic
      diseases in the Department of Pediatric Hematology and Oncology (DPHO),
      University Hospital Motol, Prague between 2005 and 2010. Risk factors for the
      development of mucormycosis, clinical symptoms and radiology and laboratory
      results were retrospectively evaluated. So were the therapy used and outcomes.
      The findings were analyzed using Fisher's exact test. RESULTS: During the
      selected period, mucormycosis was detected in 8 patients diagnosed with
      hematologic disease. The incidence of mucormycosis was 1.75 %. These conditions
      accounted for 20.6 % of all mycoses. In five patients, it was found as isolated
      infection; three cases were associated with other mycoses (one with candidiasis,
      two with aspergillosis). The most frequent underlying disease was acute leukemia;
      the most common risk factor was severe prolonged neutropenia (median duration
      21.5 days). Three of eight patients survived mucormycosis, a mortality rate of
      62.5 %. The effective therapy was amphotericin B administration in three patients
      (p = 0.02); in two of them, it was combined with radical surgery. CONCLUSION: In
      the cohort, the proportion of mucormycosis cases was surprisingly high when
      compared with other fungal diseases. Continuous surveillance of mucormycosis in
      the DPHO is needed. There was no significant influence of the combination of
      radical surgery and amphotericin B administration as compared to administration
      of amphotericin B alone. Nevertheless, according to the published data, we
      consider this approach as an optimal strategy for the management of mucormycosis
      at the present time.

PMID- 23172022
TI  - [Detection and identification of filamentous fungi causing mycoses using
      molecular genetic methods].
AB  - Methods of molecular genetics offer rapid and sensitive detection and
      identification of fungal pathogens. The currently used methods are based mainly
      on PCR. With regard to the ubiquitous presence of fungi, it is important to
      prevent contamination during the whole process, from sampling to laboratory
      analyses. Molecular genetic methods are not included among the EORTC/MSG criteria
      used for the diagnosis of invasive fungal diseases since interlaboratory
      standardization is still missing. Another reason is the use of different target
      genes for PCR. ITS sequences from rDNA clusters are recommended for DNA barcoding
      of fungi. The use of DNA sequencing for identification of fungi in clinical
      samples has certain limitations and interpretation of results could be
      problematic in some cases. DNA sequences are searched and compared in public
      databases on the Internet, the best known of them being the GenBank. However,
      more reliable data for identification of fungi are offered by specialized
      mycological databases.

PMID- 23172023
TI  - [Yeast colonization of urinary catheters and the significance of biofilm
      formation].
AB  - OBJECTIVE: Urinary catheters are colonized by a wide range of microorganisms,
      including numerous yeasts. The catheters are usually colonized by more microbial
      species forming a community - multispecies biofilm. Catheter colonization usually
      does not affect the patient's clinical status in any significant way. On the
      other hand, the biofilm can become a source of endogenous infection and its
      presence can affect functionality of the catheter and formation of urinary
      stones. Material a METHODS: A total of 721 urinary catheters were studied.
      Microorganisms were released from catheters by sonication and subsequently
      cultured. Their identification was performed with the use of common phenotypic
      tests, as well as using MALDI TOF. Yeasts whose identification was ambiguous were
      recognized by sequencing. Biofilm formation was assessed by growth in a
      microtiter plate. RESULTS AND CONCLUSION: Yeast colonization was proved in 244
      urinary catheters. However, a total of 274 yeast strains were isolated. Most of
      them occurred together with other yeast species and/or bacteria on the catheters,
      producing multispecies biofilm there. The most frequent species was Candida
      albicans (a total of 144 isolated strains), followed by Candida glabrata (41),
      Candida tropicalis (41) and Candida parapsilosis sensu stricto (14). Other
      isolated species were as follows: Candida kefyr (10), Candida krusei (9), Candida
      fabianii (6), Candida lusitaniae (5), Candida dubliniensis (3) and Saccharomyces
      cerevisiae (one case). Most of the yeasts rather readily formed a firmly adhering
      biofilm layer on artificial surfaces.

PMID- 23172024
TI  - [Practical knowledge in fungal diagnosis in some biological materials].
AB  - The article deals with certain problematic issues associated with routine
      laboratory diagnosis of mycoses from secretions and samples taken from the
      respiratory tract and maxillary sinuses as well as samples of skin and skin
      appendages. The text is based on both the author's own long-term experience and
      experience gained from cooperation with other laboratories. To improve the
      detection of filamentous fungi in lower respiratory tract secretions, it is
      recommended to use 0.5 mL of the material for individual culture media. In both
      secretions and other biological material, the role of microscopic examination is
      stressed. In many cases, this may also be the only reliable laboratory procedure.
      Detection of filamentous fungi should be interpreted in close cooperation with
      clinicians, especially in order to obtain history data. These are particularly
      important in the diagnosis of endemic mycoses. Equivocal or unusual findings
      should be verified by repeated laboratory tests.

PMID- 23172025
TI  - Air oxygenation chemistry of 4-TBC catalyzed by chloro bridged dinuclear
      copper(II) complexes of pyrazole based tridentate ligands: synthesis, structure,
      magnetic and computational studies.
AB  - Four dinuclear bis(MU-Cl) bridged copper(II) complexes, [Cu(2)(MU
      Cl)(2)(L(X))(2)](ClO(4))(2) (L(X) = N,N-bis[(3,5-dimethylpyrazole-1-yl)
      methyl]benzylamine with X = H(1), OMe(2), Me(3) and Cl(4)), have been synthesized
      and characterized by the single crystal X-ray diffraction method. In these
      complexes, each copper(II) center is penta-coordinated with square-pyramidal
      geometry. In addition to the tridentate L(X) ligand, a chloride ion occupies the
      last position of the square plane. This chloride ion is also bonded to the
      neighboring Cu(II) site in its axial position forming an SP-I dinuclear Cu(II)
      unit that exhibits small intramolecular ferromagnetic interactions and supported
      by DFT calculations. The complexes 1-3 exhibit methylmonooxygenase (pMMO)
      behaviour and oxidise 4-tert-butylcatechol (4-TBCH(2)) with molecular oxygen in
      MeOH or MeCN to 4-tert-butyl-benzoquinone (4-TBQ), 5-methoxy-4-tert-butyl
      benzoquinone (5-MeO-4-TBQ) as the major products along with 6,6'-Bu(t)-biphenyl
      3,4,3',4'-tetraol and others as minor products. These are further confirmed by
      ESI- and FAB-mass analyses. A tentative catalytic cycle has been framed based on
      the mass spectral analysis of the products and DFT calculations on individual
      intermediates that are energetically feasible.

PMID- 23172027
TI  - The morning blood pressure surge is related to serum cholesterol.
AB  - A morning blood pressure surge (MBPS) may be either a mechanism for, or a marker
      of, increased cardiovascular events. This study has examined factors which may
      influence the morning surge: age, gender, metabolic factors, sympathetic
      function, blood pressure and arterial stiffness. Four measures of the MBPS were
      examined--sleep-trough surge, pre-awake surge, rate of blood pressure rise and a
      Power function. Subjects underwent ambulatory blood pressure monitoring, glucose
      tolerance test, central pulse wave velocity, sympathetic autonomic function tests
      (mental stress and sustained handgrip). MBPS was associated with age,
      hypertension, blood pressure variability and serum lipids. After adjustment for
      age and waist circumference, all four measures of MBPS remained positively
      associated with low-density lipoprotein (LDL) cholesterol. The novel finding of a
      significant relationship between measures of MBPS and LDL-cholesterol is an
      intriguing link between two major cardiovascular risk factors.

PMID- 23172026
TI  - Effect of resistance training on biomarkers of vascular function and oxidative
      stress in young African-American and Caucasian men.
AB  - African Americans (AA) have an earlier onset of hypertension and a different
      vascular profile than their Caucasian (Cau) peers. Research suggests that
      biological mediators of vascular inflammation are different among these groups in
      hypertensive populations. Resistance training (RT) is an important exercise
      modality that improves the vascular profile of young AA men. We examined the role
      of RT on biomarkers of vascular function and oxidative stress in body mass index
      matched AA and Cau men. RT for 6 weeks elicited significant changes in
      circulating matrix metalloprotease-9 (MMP-9) and 8-Isoprostane (8-IsoP) in young
      AA men (n=14, AA; n=18, Cau; 18-35 years). MMP-9 was lower and decreased in AA
      (pre: P=0.02; post: P<0.001) and a time * group interaction for MMP-9 (F(1,
      30)=4.81; P=0.036) and 8-IsoP (F(1, 24)=7.09; P=0.014) was detected. 8-IsoP
      decreased in AA (P=0.026) but did not change in Cau (P=0.309). Notably, the
      increase in strength (1-repetition maximum (1-RM)) was correlated with the
      decrease in MMP-9 (r=-0.398; P=0.022). Furthermore, these adaptations were
      independent of any improvement in cardiorespiratory fitness. We demonstrate that
      RT effectively reduces matrix remodeling proteins and oxidative stress in young
      AA men. Increasing strength may be beneficial for improving vascular health and
      offsetting novel cardiovascular risk factors of hypertension in young AA men.

PMID- 23172028
TI  - Unsafe health and safety: sphygmomanometer cuffs are not interchangeable.
AB  - Unknown to its hypertension specialists, a major teaching hospital changed the
      cuffs on its sphygmomanometers from manufacturer-validated to a uniform washable
      alternative, in line with 'Health and Safety' concerns surrounding potential
      cross-contamination between patients. When clinic doctors suspected serious under
      reading with the new cuffs, a systematic comparison was undertaken in 54 patients
      (mean+/-s.d. age, 61+/-17 years), using two UM-101 sphygmomanometers, one using
      the original, manufacturer-supplied cuff and the other with the washable
      replacement. The study confirmed an average under-reading of 8+/-10/5+/-5 mm Hg
      using the washable cuff, and a third of patients with poorly controlled
      hypertension were considered normotensive, after using this cuff. The UM-101
      sphygmomanometers have now been re-fitted with the original cuffs.
      Sphygmomanometer cuffs are not interchangeable between devices and a modicum of
      common sense should be shown to prevent changes made in the name of Health and
      Safety from having the opposite effect to that intended.

PMID- 23172029
TI  - Involvement of cytochrome epoxygenase metabolites in cutaneous postocclusive
      hyperemia in humans.
AB  - Several mediators contribute to postocclusive reactive hyperemia (PORH) of the
      skin, including sensory nerves and endothelium-derived hyperpolarizing factors.
      The main objective of our study was to investigate the specific contribution of
      epoxyeicosatrienoic acids in human skin PORH. Eight healthy volunteers were
      enrolled in two placebo-controlled experiments. In the first experiment we
      studied the separate and combined effects of 6.5 mM fluconazole, infused through
      microdialysis fibers, and lidocaine/prilocaine cream on skin PORH following 5 min
      arterial occlusion. In the second experiment we studied the separate and combined
      effects of 6.5 mM fluconazole and 10 mM N(G)-monomethyl-l-arginine (l-NMMA). Skin
      blood flux was recorded using two-dimensional laser speckle contrast imaging.
      Maximal cutaneous vascular conductance (CVC(max)) was obtained following 29 mM
      sodium nitroprusside perfusion. The PORH peak at the placebo site averaged 66 +/-
      11%CVC(max). Compared with the placebo site, the peak was significantly lower at
      the fluconazole (47 +/- 10%CVC(max); P < 0.001), lidocaine (29 +/- 10%CVC(max); P
      < 0.001), and fluconazole + lidocaine (30 +/- 10%CVC(max); P < 0.001) sites. The
      effect of fluconazole on the area under the curve was more pronounced. In the
      second experiment, the PORH peak was significantly lower at the fluconazole site,
      but not at the l-NMMA or combination site, compared with the placebo site. In
      addition to sensory nerves cytochrome epoxygenase metabolites, putatively
      epoxyeicosatrienoic acids, play a major role in healthy skin PORH, their role
      being more important in the time course rather than the peak.

PMID- 23172030
TI  - Prevention of deep tissue injury through muscle contractions induced by
      intermittent electrical stimulation after spinal cord injury in pigs.
AB  - Deep tissue injury (DTI) is a severe medical complication that commonly affects
      those with spinal cord injury. It is caused by prolonged external loading of the
      muscles, entrapping them between a bony prominence and the support surface. The
      entrapment causes excessive mechanical deformation and increases in interstitial
      pressure, leading to muscle breakdown deep around the bony prominences. We
      proposed the use of intermittent electrical stimulation (IES) as a novel
      prophylactic method for the prevention of DTI. In this study, we assessed the
      long-term effectiveness of this technique in pigs that had received a partial
      spinal cord injury that paralyzed one hindlimb. The pigs recovered for 2 wk
      postsurgery, and subsequently, their paralyzed limbs were loaded to 25% of their
      body weights 4 h/day for 4 consecutive days each week for 1 mo. One group of pigs
      (n = 3) received IES during the loading, whereas another group (n = 3) did not.
      DTI was quantified using magnetic resonance imaging (MRI) and postmortem
      histology. In the group that did not receive IES, MRI assessments revealed signs
      of tissue damage in 48% of the volume of the loaded muscle. In the group that did
      receive IES, only 8% of the loaded muscle volume showed signs of tissue damage.
      Similar findings were found through postmortem histology. This study
      demonstrates, for the first time, that IES may be an effective technique for
      preventing the formation of DTI in loaded muscles after spinal cord injury.

PMID- 23172031
TI  - Role of dual-specificity protein phosphatase-5 in modulating the myogenic
      response in rat cerebral arteries.
AB  - The present study examined the role of the dual-specificity protein phosphatase-5
      (DUSP-5) in the pressure-induced myogenic responses of organ-cultured cerebral
      arterial segments. In these studies, we initially compared freshly isolated and
      organ-cultured cerebral arterial segments with respect to responses to step
      increases in intravascular pressure, vasodilator and vasoconstrictor stimuli,
      activities of the large-conductance arterial Ca(2+)-activated K(+) (K(Ca)) single
      channel current, and stable protein expression of DUSP-5 enzyme. The results
      demonstrate maintained pressure-dependent myogenic vasoconstriction, DUSP-5
      protein expression, endothelium-dependent and -independent dilations, agonist
      induced constriction, and unitary K(Ca) channel conductance in organ-cultured
      cerebral arterial segments similar to that in freshly isolated cerebral arteries.
      Furthermore, using a permeabilization transfection technique in organ-cultured
      cerebral arterial segments, gene-specific small interfering RNA (siRNA) induced
      knockdown of DUSP-5 mRNA and protein, which were associated with enhanced
      pressure-dependent cerebral arterial myogenic constriction and increased
      phosphorylation of PKC-betaII. In addition, siRNA knockdown of DUSP-5 reduced
      levels of phosphorylated ROCK and ERK1 with no change in the level of
      phosphorylated ERK2. Pharmacological inhibition of ERK1/2 phosphorylation
      significantly attenuated pressure-induced myogenic constriction in cerebral
      arteries. The findings within the present studies illustrate that DUSP-5, native
      in cerebral arterial muscle cells, appears to regulate signaling of pressure
      dependent myogenic cerebral arterial constriction, which is crucial for the
      maintenance of constant cerebral blood flow to the brain.

PMID- 23172036
TI  - Concurrent sexual partnerships among female sex workers and their non-commercial
      male partners in Tijuana and Ciudad Juarez, Mexico.
AB  - OBJECTIVES: To investigate the prevalence and correlates of concurrent
      (overlapping) sexual partnerships among female sex workers (FSWs) and their non
      commercial male partners in two Mexico-US border cities. METHODS: A cross
      sectional survey of FSWs and their non-commercial male partners was conducted in
      Tijuana and Ciudad Juarez, Mexico (2010-2011). Eligible FSWs and verified non
      commercial partners were aged >=18 years; FSWs had ever used hard drugs
      (lifetime) and recently exchanged sex for money, drugs or other goods (past
      month). Participants underwent baseline questionnaires obtaining dates of sex and
      condom use with <=5 other recurring partners, including FSWs' regular clients.
      These dates were compared with dates of sex with enrolled study partners to
      determine overlap (ie, 'recurring' concurrency). Bivariate probit regression
      identified recurring concurrency correlates. RESULTS: Among 428 individuals (214
      couples), past-year recurring concurrency prevalence was 16% and was higher among
      women than their non-commercial male partners (26% vs 6%). In 10 couples (5%),
      both partners reported recurring concurrency. The majority of couples (64%)
      always had unprotected sex, and most of the individuals (70%) with recurring
      concurrency 'sometimes' or 'never' used condoms with their concurrent partners.
      Recurring concurrency was positively associated with FSWs' income, men's
      caballerismo (a form of traditional masculinity) and men's belief that their FSW
      partners had sexually transmitted infections (STIs). CONCLUSIONS: Recurring
      concurrency, representing sustained periods of overlapping partnerships in which
      unprotected sex was common, should be addressed by couple-based STI prevention
      interventions.

PMID- 23172037
TI  - Promoter hypomethylation of TIMP3 is associated with pre-eclampsia in a Chinese
      population.
AB  - A study by Yuen RK, Penaherrera MS, von Dadelszen P, McFadden DE, Robinson WP.
      DNA methylation profiling of human placentas reveals promoter hypomethylation of
      multiple genes in early-onset preeclampsia. Eur J Hum Genet 2010;18:1006-1012
      based on a Canadian population found the tissue inhibitor of the
      metalloproteinase 3 (TIMP3) gene to be hypomethylated in pre-eclampsia (PE)
      placentas and to be a potential prenatal marker for early onset PE. To further
      explore the role of TIMP3 in PE and to investigate whether the TIMP3 promoter
      shows the same methylation pattern in the Han Chinese population, we analyzed a
      complete methylation assay of TIMP3 including the promoter region studied in the
      Canadian report and the neighboring CpG island in placentas (cases n = 41,
      controls n = 22) maternal peripheral blood (cases n = 3; controls n = 6) and
      umbilical cord blood (cases n = 7; controls n = 8) using MassArray EpiTyper
      (Sequenom, San Diego, CA, USA). Our results confirmed the finding of aberrant
      TIMP3 promoter methylation in PE placentas (mean = 0.405) compared with those in
      controls (mean = 0.534, P = 9.40 * 10(-7)). A tissue-specific methylation pattern
      between placentas (mean = 0.459) and bloods (mean = 0.961, P = 6.91 * 10(-13))
      was also demonstrated in our clinical samples. Furthermore, a nearly 2-fold
      increase in TIMP3 expression for the hypomethylated promoter was found in PE
      placentas (P = 0.007), pointing to a negative relationship between TIMP3
      methylation and the expression (R = -0.758, P = 0.029). In conclusion, we
      replicated the findings of Yuen et al. in our Han Chinese-based study, confirming
      that TIMP3 is likely to be involved in the etiology of PE and that hypomethylated
      and placenta-specific TIMP3 may be a potential marker for early diagnosis of PE
      in maternal plasma.

PMID- 23172038
TI  - Predicting isosteric heats for gas adsorption.
AB  - A method for predicting the isosteric heat of gas adsorption on solid materials
      is developed which requires the measurement of a single isotherm - where previous
      methods, such as the Clausius-Clapeyron approach, require either multiple
      isotherms or complex calorimetric measurement. The Toth potential function,
      stemming from the Polanyi potential function, is evaluated using the Langmuir and
      Toth isotherm equations to generate new equations for the isosteric heat. These
      new isosteric heat equations share common parameters with the isotherm equations
      and are determined from isotherm fitting. This method is demonstrated in the
      literature for gas adsorption onto solid adsorbates including zeolites of various
      surface charge character and non-porous rutile phase titanium dioxide.
      Predictions are made using the new isosteric heat equations and then compared to
      calorimetric data.

PMID- 23172039
TI  - Nasal polyposis:  an inflammatory condition requiring effective anti-inflammatory
      treatment.
AB  - PURPOSE OF REVIEW: Recent literature in chronic rhinosinusitis with nasal polyps
      (CRSwNP) has focussed on inflammatory mechanisms underlying the disease.
      Endotyping the histopathological features of the disease, rather than simple
      clinical phenotypes, reflects a change in our understanding of the disease and
      approach to management. This is paralleled by renewed evidence for the need for
      wide postsurgical access and topical anti-inflammatory therapy. RECENT FINDINGS:
      Recent research into patterns of dysfunction in innate immunity suggests a
      crucial role of respiratory epithelium in mediating the inflammatory response.
      Elevated interleukins, IL-25 and IL-33, from sinus mucosa in CRSwNP and their
      interaction via innate lymphoid cells may represent the link between the host
      environment interface and T-helper 2 dominated inflammation that characterizes
      CRSwNP. While thorough immunological profiling of CRSwNP is not routinely
      available, classification of CRS as eosinophilic (ECRS) or noneosinophilic is
      practical and correlates with disease severity and prognosis. The practice and
      utility of endoscopic sinus surgery to create a single neosinus for topical
      corticosteroid delivery is a logical conclusion founded on the inflammatory basis
      of CRSwNP/ECRS. SUMMARY: There is mounting evidence for CRSwNP as a predominantly
      inflammatory disease. Even simple histopathological classification on the basis
      of degrees of tissue eosinophilia reflects the underlying pathogenic mechanisms
      with diagnostic and prognostic implications. Optimal treatment involves topical
      anti-inflammatory therapy delivered locally via a wide, postsurgical corridor.

PMID- 23172040
TI  - A thickened formula does not reduce apneas related to gastroesophageal reflux in
      preterm infants.
AB  - BACKGROUND: Apnea of prematurity (AOP) occurs frequently in preterm infants and a
      variable proportion of AOP can be induced by gastroesophageal reflux (GER).
      Conservative treatment, including dietary modifications, should be the first-line
      approach for both GER and GER-related apneas in this population. OBJECTIVES: To
      evaluate the efficacy of a starch-thickened preterm formula (PF) in reducing the
      frequency of apneas related to GER. METHODS: Preterm infants with AOP were
      studied by combined impedance and pH monitoring and polysomnography. The 6-hour
      study period included two feeds, one of a commercially available PF and one of
      the same formula thickened with amylopectin (TPF). GER indexes, apneas and GER
      related apneas detected after TPF and PF feeds were compared by Wilcoxon signed
      rank test. RESULTS: 24 infants were studied. During 140 h of registration, 289
      apneas (147 after TPF and 142 after PF; p = 0.876), and 861 GER episodes (400
      after TPF and 461 after PF; p = 0.465) were recorded. No difference in the number
      of AOP was found between TPF and PF. A significant reduction in acid exposure was
      found after TPF; there was no influence on non-acid GER indexes. The frequency of
      GER-related apneas did not differ between TPF and PF. CONCLUSIONS: A formula
      thickened with amylopectin did not reduce the number of AOP or GER-related
      apneas. It reduced acid GER features but had no effect on non-acid GER indexes.
      Future research should focus on exploring different conservative strategies to
      treat GER-related apneas in preterm infants.

PMID- 23172041
TI  - A novel amperometric immunosensor constructed with gold-platinum nanoparticles
      and horseradish peroxidase nanoparticles as well as nickel hexacyanoferrates
      nanoparticles.
AB  - In this study, three nano-materials comprising gold-platinum nanoparticles (Au
      PtNPs), horseradish peroxidase nanoparticles (HRPNPs) and nickel hexacyanoferrate
      nanoparticles (NiHCFNPs) were used to construct a signal-off immunosensor. Au
      PtNPs and NiHCFNPs were assembled on a glass carbon electrode (GCE) by
      electrodeposition and gold-cyanide bond formation, respectively; anti
      fetoproteins (anti-AFP) were immobilized on the Au-PtNPs. HRPNPs were employed to
      block the possible remaining active sites and avoid nonspecific adsorption. Here,
      NiHCFNPs served as redox probes, while Au-PtNPs and HRPNPs were used for the
      synergistic catalysis of H(2)O(2) to amplify the signal. With more and more
      immunocomplex produced by the antibody-antigen reaction covering the biosensing
      surface, thus hindering electron transfer, the catalytic peak current will
      decrease quantitatively in relation to the concentration of target antigen. The
      resulting immunosensors exhibited a fast response and excellent sensitivity to
      alpha-fetoprotein (AFP), and showed two linear ranges in the concentration ranges
      of 0.06-13 ng mL(-1) and 13-200 ng mL(-1) with a detection limit of 0.017 ng mL(
      1).

PMID- 23172042
TI  - Longitudinal study of seroprevalence and serostability of the human
      polyomaviruses JCV and BKV in organ transplant recipients.
AB  - The human polyomaviruses BKV and JCV cause mostly subclinical infections in
      childhood. Systemical immunosuppression after organ transplantation can lead to
      reactivation of persistent polyomavirus infections which may cause rejection of
      the transplanted organ. BKV and JCV seroprevalence and serostability was measured
      in 441 European solid organ transplanted recipients. Baseline samples were
      collected on average 24 days post-transplantation and sera were then collected
      over an 18 months follow-up period on up to six different time points. The
      overall seroprevalence at baseline for BKV was 97% with very little change over
      time. Prevalence for JCV was 76% at baseline and increased to 80% at the end of
      follow-up. BKV seroprevalence was highest in the youngest age group (100%) and
      decreased with increasing age (92% in the oldest age group; P < 0.0001), while
      JCV increased with age (69% vs. 81%; P = 0.020). Antibody reactivities for both
      BKV and JCV increased significantly with time (P = 0.0002 and P < 0.0001,
      respectively). Among the 406 patients with several samples, 94% were stably
      seropositive for BKV and 1% remained seronegative during the follow-up. JCV
      antibody stability was somewhat lower: 67% remained stably seropositive and 13%
      seronegative. While seroprevalence of BKV and JCV decrease and increase with age,
      respectively, both polyomaviruses showed significant increasing antibody
      reactivity over time in organ transplanted recipients at the onset of
      immunosuppression.

PMID- 23172043
TI  - Cytoskeletal changes during development and aging in the cortex of neurofilament
      light protein knockout mice.
AB  - The neurofilament light (NFL) subunit is considered as an obligate subunit
      polymer for neuronal intermediate filaments comprising the neurofilament (NF)
      triplet proteins. We examined cytoskeletal protein levels in the cerebral cortex
      of NFL knockout (KO) mice at postnatal day 4 (P4), 5 months, and 12 months of age
      compared with age-matched wild-type (WT) mice of a similar genetic background
      (C57BL/6). The absence of NFL protein resulted in a significant reduction of
      phosphorylated and dephosphorylated NFs (NF-P, NF-DP), the medium NF subunit
      (NFM), and the intermediate filament alpha-internexin (INT) at P4. At 5 months,
      NF-DP, NFM, and INT remained significantly lower in knockouts. At 12 months, NF-P
      was again significantly decreased, and INT significantly increased, in KOs
      compared with wild type. In addition, protein levels of class III neuron-specific
      beta-tubulin and microtubule-associated protein 2 were significantly increased in
      NFL KO mice at P4, 5 months, and 12 months, whereas beta-actin levels were
      significantly decreased at P4. Immunocytochemical studies demonstrated that NF-DP
      accumulated abnormally in the perikarya of cortical neurons by 5 months of age in
      NFL KO mice. Neurons that lacked NF triplet proteins, such as calretinin
      immunolabeled nonpyramidal cells, showed no alterations in density or
      cytoarchitectural distribution in NFL KO mice at 5 months relative to WT mice,
      although calretinin protein levels were decreased significantly after 12 months
      in NFL KO mice. These findings suggest that a lack of NFL protein alters the
      expression of cytoskeletal proteins and disrupts other NF subunits, causing
      intracellular aggregation but not gross structural changes in cortical neurons or
      cytoarchitecture. The data also indicate that changes in expression of other
      cytoskeletal proteins may compensate for decreased NFs.

PMID- 23172044
TI  - Agreement between magnetic resonance imaging, myelography, and surgery for
      detecting recurrent, thoracolumbar intervertebral disc extrusion in dogs.
AB  - OBJECTIVES: Although magnetic resonance imaging (MRI) is reported to be superior
      to myelography to determine the location and site of first time disc herniation,
      comparison of these diagnostic methods in cases of recurrent intervertebral disc
      disease (IVD) herniation after a first surgery has not been evaluated. The
      objective was to compare the diagnostic accuracy of MRI and myelography in a
      series of dogs undergoing repeat surgical decompression for recurrent IVD
      extrusion when compared to the gold standard of surgery. METHODS: Ten dogs with
      recurrent IVD herniation underwent MRI and myelography followed by surgical
      decompression. Three observers reviewed the images to determine the site and side
      of the first surgery and the recurrent lesion. Agreement was determined by
      calculating a kappa (kappa) score. RESULTS: Substantial interobserver agreement
      was noted for recurrent lesion site using MRI and myelography (kappa = 0.77 vs.
      0.73) and when comparing MRI and myelography to the reported surgical site (kappa
      = 0.73 vs. 0.67). Interobserver agreement was greater with MRI for
      circumferential location compared to myelography (kappa = 0.76 vs. 0.43), similar
      to what was found when comparing to surgical side (kappa = 0.82 vs. 0.49). The
      previous surgical site in this study had no effect on ability to identify the new
      lesion. CLINICAL SIGNIFICANCE: Despite the limitations of MRI, there was greater
      agreement between observers using MRI for both the recurrent and first lesion.

PMID- 23172047
TI  - When falsified medicines enter the supply chain: description of an incident in
      Kenya and lessons learned for rapid response.
AB  - Falsified and substandard medicines present serious concerns for public health.
      We describe an event that occurred in late 2011 involving falsified
      antiretroviral medicines found in the supplies of Medecins Sans Frontieres (MSF)
      projects in Kenya. We discuss factors contributing to these falsified medicines
      entering the supply chain as well as the response by MSF and others. We make
      recommendations to help defend against future episodes of entry of falsified
      medicines into the supply chain as well as comments on appropriate responses in
      cases of falsified medicines.

PMID- 23172048
TI  - Commentary: Corporate philanthropy and conflicts of interest in public health.
AB  - This commentary discusses how ethicists view the responsibilities of
      corporations, of their philanthropic spin-offs, and of not-for-profit
      organizations with regard to use of monies from corporate philanthropies for
      public health. Article JPHP.2012.60 available at www.palgrave-journals.com/jphp/,
      relates to this commentary.

PMID- 23172049
TI  - Social enterprise: new pathways to health and well-being?
AB  - In this article we attempt to make sense of recent policy directions and
      controversies relating to the 'social enterprise' and 'health' interface. In
      doing so, we outline the unrecognised potential of social enterprise for
      generating health and well-being improvement, and the subsequent challenges for
      government, the sector itself, and for the research community. Although we focus
      primarily upon the U.K. policy landscape, the key message--that social enterprise
      could represent an innovative and sustainable public health intervention--is a
      useful contribution to the ongoing international debate on how best to address
      the challenge of persistent and widening health inequalities.

PMID- 23172050
TI  - Corporate philanthropy and conflicts of interest in public health: ExxonMobil,
      Equatorial Guinea, and malaria.
AB  - Equatorial Guinea, the most prosperous country in Africa, still bears a large
      malaria burden. With massive wealth from oil reserves, and nearly half its
      population living in island ecotypes favourable for malaria control, only poor
      governance can explain continued parasite burden. By financially backing the
      country's dictator and other officials through illicit payments, the oil company
      ExxonMobil contributed to the state's failure. Now ExxonMobil, having helped
      perpetuate malaria in Equatorial Guinea, gives money to non-governmental
      organizations, charitable foundations, and universities to advocate for and
      undertake malaria work. How, and on what terms, can public health engage with
      such an actor? We discuss challenges in the identification and management of
      conflicts of interest in public health activities. We reviewed the business and
      foundation activities of ExxonMobil and surveyed organizations that received
      ExxonMobil money about their conflict of interest policies. Reforms in
      ExxonMobil's business practices, as well as its charitable structure, and reforms
      in the way public health groups screen and manage conflicts of interest are
      needed to ensure that any relationship ultimately improves the health of
      citizens.

PMID- 23172051
TI  - Comparison of health policy documents of European cities: are they oriented to
      reduce inequalities in health?
AB  - Health policies are specified in documents that contain values, objectives,
      strategies, and interventions to be implemented. The objective of our study was
      to analyse health policy documents of six European cities and one county council
      published around 2010 to determine (i) how cities conceptualize health
      inequalities, and (ii) what strategies are proposed to reduce them. We performed
      a qualitative document analysis. We selected Health or Health Inequalities policy
      documents and analysed the following aspects: general characteristics of the
      document, inclusion and definition of health inequalities, promotion of good
      governance and participation, number of objectives, and evaluation. We also
      described specific objectives. Rotterdam, London, and Stockholm use a conceptual
      framework. Two of them define health inequalities as a social gradient.
      Intersectoral action, participation, and evaluation are included in most
      documents. Interventions focus mainly on the socioeconomic context.

PMID- 23172052
TI  - MicroRNA expression profiles in metastatic and non-metastatic giant cell tumor of
      bone.
AB  - Giant cell tumor of bone (GCTB) is a skeletal neoplasm, a locally aggressive
      tumor that occasionally metastasizes to the lungs. To identify novel biomarkers
      associated with GCTB progression and metastasis, we performed a miRNA microarray
      on ten primary tumors of GCTB, of which five developed lung metastases and the
      rest remained metastasis-free. Between metastatic and non-metastatic GCTB, 12
      miRNAs were differentially expressed (such as miR-136, miR-513a-5p, miR-494, miR
      224, and miR-542-5p). A decreased level of miR-136 in metastatic versus non
      metastatic GCTB was significantly confirmed by the quantitative reverse
      transcriptase polymerase chain reaction (qRT-PCR) (p=0.04). To identify potential
      target genes for the differentially expressed miRNAs, we used three target
      prediction databases. Then, to functionally validate the potential target genes
      of the differentially expressed miRNAs, we re-analyzed our previous gene
      expression data from the same ten patients. Eight genes such as NFIB, TNC, and
      FLRT2 were inversely expressed relative to their predicted miRNA regulators. NFIB
      expression correlated in metastatic GCTB with no or low expression of miR-136,
      and this gene was selected for further verification with qRT-PCR and
      immunohistochemistry. Verification of NFIB mRNA and protein by qRT-PCR showed
      elevated expression levels in metastatic GCTBs. Further, the protein expression
      level of NFIB was tested in an independent validation cohort of 74 primary
      archival GCTB specimens. In the primary tumors that developed metastases compared
      to the disease-free group, NFIB protein was moderately to strongly expressed at a
      higher frequency. Thus, in GCTB, miR-136 and NFIB may serve as prognostic makers.

PMID- 23172053
TI  - Continuing education.

PMID- 23172058
TI  - Learning on the streets: experiencing homelessness.

PMID- 23172061
TI  - Kidney stones.

PMID- 23172062
TI  - A Christmas story.

PMID- 23172064
TI  - Making repairs with endovascular surgical neuroradiology.

PMID- 23172065
TI  - Policy and politics: why nurses should get involved.

PMID- 23172066
TI  - Takotsubo cardiomyopathy: nursing a broken heart.

PMID- 23172067
TI  - To B or not to B? The inside scoop on vitamin B12.

PMID- 23172068
TI  - Recognizing poststroke depression.

PMID- 23172069
TI  - Facing up to the challenge of range orders.

PMID- 23172070
TI  - Intermittent I.V. infusions in acute care: special considerations.

PMID- 23172071
TI  - What's new in the UA/NSTEMI guidelines?

PMID- 23172073
TI  - Bleeding esophageal varices.

PMID- 23172074
TI  - Terrestrial foraging by Cacajao melanocephalus ouakary (primates) in Amazonian
      Brazil: is choice of seed patch size and position related to predation risk?
AB  - We analyse the behaviour of Cacajao melanocephalus ouakary feeding at patches of
      germinating seedlings in dried-out flooded forest. Seedlings of Eschweilera
      tenuifolia (Lecythidaceae) were the most commonly eaten (88.9%). Some seed
      patches were revisited over several days, while others were consistently ignored.
      We tested 3 predictions relating uacari terrestrial foraging behaviour to: (1)
      arboreal escape route proximity, (2) seed patch size choice and (3) temporal
      patterns of repeat exploitation. Comparison of fed-at and ignored patches
      revealed significant preferences for larger patches, and for those close to
      arboreal refuges but distant from dense ground-based vegetation. Support for
      these predictions is interpreted as evidence for predation risk-sensitive
      foraging.

PMID- 23172075
TI  - Computational studies on organic reactivity in ionic liquids.
AB  - Computational studies on organic reactions in ionic liquids (ILs) are analysed
      from different points of view. Important information about reaction mechanisms in
      ILs has been obtained from these studies although the theoretical approaches are
      still not able to give an exhaustive picture of the chemical processes occurring
      in ionic media. Challenges and perspectives of this investigation field are
      discussed and the fundamental role played by experimental results in the
      development of this intriguing sector is pointed out.

PMID- 23172077
TI  - Gastroesophageal reflux and apnea of prematurity--coincidence, not causation.
      Commentary on L. Corvaglia et Al.: A thickened formula does not reduce apneas
      related to gastroesophageal reflux in preterm infants (Neonatology 2013;103;98
      102).

PMID- 23172078
TI  - Encapsulation and release of hydrophobic bioactive components in nanoemulsion
      based delivery systems: impact of physical form on quercetin bioaccessibility.
AB  - Many bioactive compounds are hydrophobic materials that are crystalline at
      ambient and body temperatures, which reduces their bioavailability and poses
      challenges to their successful incorporation into pharmaceuticals and functional
      foods. The aim of this study was to determine whether a hydrophobic crystalline
      bioactive component (quercetin) could be successfully incorporated into
      nanoemulsion-based delivery systems, and to evaluate the extent to which these
      delivery systems altered its bioaccessibility. The maximum amount of soluble
      quercetin that could be loaded into a carrier oil phase (medium chain
      triglycerides, MCT) at ambient temperature was C(Sat)~ 0.15 mg mL(-1). At
      quercetin concentrations <C(Sat), nanoemulsions remained stable throughout 30
      days storage at 5, 20 and 37  degrees C, i.e., no droplet growth, droplet
      creaming, or crystal formation were observed. At quercetin concentrations
      >C(Sat), nanoemulsions remained physically stable (no droplet growth or
      creaming), but quercetin crystals formed in the samples during storage. The
      bioaccessibility of quercetin was determined using an in vitro digestion model
      simulating the mouth, stomach, and small intestine. A higher percentage of
      quercetin was solubilized in the micelle phase after small intestine digestion
      when it was incorporated in nanoemulsions than when it was dispersed in either
      bulk oil or pure water. The bioaccessibility of crystalline quercetin was less
      than that of dissolved quercetin. The knowledge gained from this study is
      valuable for the rational design of delivery systems to incorporate crystalline
      hydrophobic bioactive compounds into pharmaceuticals and functional foods, and to
      increase their bioaccessibility.

PMID- 23172079
TI  - A gold nanorods-based fluorescent biosensor for the detection of hepatitis B
      virus DNA based on fluorescence resonance energy transfer.
AB  - In this study, we designed a fluorescence resonance energy transfer system
      containing gold nanorods (AuNRs) and fluorescein (FAM) for the detection of
      hepatitis B virus DNA sequences. AuNRs were synthesized according to the seed
      mediated surfactant-directed approach, and the surface of the AuNRs was wrapped
      with a thin layer of cetyltrimethylammonium bromide (CTAB), resulting in the
      AuNRs being positively charged. When FAM-tagged single-stranded DNA (FAM-ssDNA)
      was added into the AuNRs suspension, it was adsorbed onto the surface of the
      positively charged AuNRs and formed a FAM-ssDNA-CTAB-AuNRs ternary complex, the
      resulting structure led to a fluorescence resonance energy transfer (FRET)
      process from FAM to AuNRs and the fluorescence intensity of FAM was consequently
      quenched. When complementary target DNA was added to the FAM-ssDNA-CTAB-AuNRs
      complex solution, a further decrease in fluorescence intensity was observed
      because of an increased FRET efficiency. Under optimal conditions, the decline of
      the fluorescence intensity of FAM (DeltaF) was linear with the concentration of
      the complementary DNA from 0.045 to 6.0 nmol L(-1) and the detection limit was as
      low as 15 pmol L(-1) (signal/noise ratio of 3). When this fluorescent DNA sensor
      was used to detect the polymerase chain reaction product of hepatitis B virus
      gene extracted from a positive real sample, a positive response was obtained.
      Impressively, the biosensor exhibits good selectivity, even for single-mismatched
      DNA detection.

PMID- 23172081
TI  - Nrf2 expression is associated with poor outcome in osteosarcoma.
AB  - AIMS: NF-E2-related factor 2 (Nrf2) is involved in defence against oxidative
      stress in human cells. Nrf2 is over-expressed in many types of cancers suggesting
      that it plays a role in carcinogenesis and chemoresistance. We examined Nrf2
      expression in osteosarcoma to determine its prognostic significance. METHODS:
      Nrf2 expression was assessed using immunohistochemistry in 58 specimens from
      patients with osteosarcoma. We investigated whether Nrf2 expression was
      associated with clinicopathological parameters. RESULTS: Nrf2 was positively
      expressed in 19 (32.8%) of 58 specimens. Nrf2 expression in osteosarcoma
      indicated a poor prognostic outcome (p  = 0.0074), and correlated with worse
      disease-free survival (p  =   0.0279). Nrf2 expression had a significant
      relationship with histological subtype (osteoblastic versus non-osteoblastic, p 
      = 0.042); the non-osteoblastic subtype showed a higher rate of Nrf2 expression
      (50.0%) than the osteoblastic subtype (23.7%). Nrf2 expression showed no
      significant relationship with response to neoadjuvant chemotherapy (p  =  0.115).
      Other clinicopathological parameters had no relationship with Nrf2 expression.
      CONCLUSION: Increased expression of Nrf2 is associated with a poor outcome and
      disease-free survival in osteosarcoma. Our results suggest that Nrf2 is a
      possible marker of poor prognosis in osteosarcoma.

PMID- 23172082
TI  - Differential expression of the Bcl-2 and Bax isoforms in CD19 positive B
      lymphocytes isolated from patients diagnosed with chronic lymphocytic leukaemia.
AB  - AIM: To examine the relative gene expression levels of the anti-apoptotic Bcl
      2alpha and beta isoforms and the pro-apoptotic Baxalpha and beta isoforms in
      patients with chronic lymphocytic leukaemia (CLL) and healthy controls (HC).
      METHODS: Peripheral blood was obtained from 36 patients diagnosed with CLL and 10
      HC. CD19 B-lymphocytes were isolated using an antibody coupled magnetic bead
      isolation system; from these cells the total RNA was isolated and purified. The
      relative levels of gene expression were examined by quantitative real-time
      polymerase chain reaction (qReTi-PCR) using primers specific for each isoform.
      RESULTS: Bcl-2alpha and Baxalpha are expressed at higher levels than their beta
      isoforms in CLL and HC. Bcl-2alpha, Bcl-2beta and Baxbeta expression is increased
      in CLL while Bax-alpha is expressed at similar levels to HC. The Bcl-2alpha/Bcl
      2beta ratio is similar in CLL and HC. The Bcl-2alpha/Baxalpha ratio is increased
      in CLL when compared with HC. CONCLUSION: Bcl-2alpha and Baxalpha appear to be
      the dominant anti- and pro-apoptotic isoforms in CLL. The Bcl-2alpha/Baxalpha
      ratio is increased in CLL while the Bcl-2alpha/Bcl-2beta ratio is similar to HC.

PMID- 23172080
TI  - Periadolescent maturation of the prefrontal cortex is sex-specific and is
      disrupted by prenatal stress.
AB  - The prefrontal cortex (PFC) undergoes dramatic, sex-specific maturation during
      adolescence. Adolescence is a vulnerable window for developing mental illnesses
      that show significant sexual dimorphisms. Gestational stress is associated with
      increased risk for both schizophrenia, which is more common among men, and
      cognitive deficits. We have shown that male, but not female, rats exposed to
      prenatal stress develop postpubertal deficits in cognitive behaviors supported by
      the prefrontal cortex. Here we tested the hypothesis that repeated variable
      prenatal stress during the third week of rat gestation disrupts periadolescent
      development of prefrontal neurons in a sex-specific fashion. Using Golgi-Cox
      stained tissue, we compared dendritic arborization and spine density of prelimbic
      layer III neurons in prenatally stressed and control animals at juvenile (day
      20), prepubertal (day 30), postpubertal (day 56), and adult (day 90) ages (N =
      115). Dendritic ramification followed a sex-specific pattern that was disrupted
      during adolescence in prenatally stressed males, but not in females. In contrast,
      the impact of prenatal stress on the female PFC was not evident until adulthood.
      Prenatal stress also caused reductions in brain and body weights, and the latter
      effect was more pronounced among males. Additionally, there was a trend toward
      reduced testosterone levels for adult prenatally stressed males. Our findings
      indicate that, similarly to humans, the rat PFC undergoes sex-specific
      development during adolescence and furthermore that this process is disrupted by
      prenatal stress. These findings may be relevant to both the development of normal
      sex differences in cognition as well as differential male-female vulnerability to
      psychiatric conditions.

PMID- 23172083
TI  - Calibration of doxycycline for use in urinary tract infections with enterococci.

PMID- 23172084
TI  - KRAS mutation analysis in a complex molecular diagnostic referral practice:  the
      need for test redundancy.

PMID- 23172085
TI  - An unusual association of calcifying pseudoneoplasm of the neuraxis with
      interhemispheric lipoma and agenesis of corpus callosum.

PMID- 23172086
TI  - Histopathological features of cutaneous drug reactions to vemurafenib:  a report
      of two cases.

PMID- 23172087
TI  - Cellular blue naevus involving the urinary bladder.

PMID- 23172088
TI  - CD3 expression in plasma cell neoplasm (multiple myeloma):  a diagnostic pitfall.

PMID- 23172089
TI  - Purple bowel discovered at autopsy.

PMID- 23172090
TI  - [Factorial structure of the dysexecutive questionnaire in a sample of the Spanish
      population with acquired brain injury and memory deficit complaints].
AB  - INTRODUCTION AND AIMS: The dysexecutive questionnaire (DEX) has been used to
      study executive deficits in both clinical samples (both psychiatric and
      neurological) and non-clinical samples, although agreement on its factorial
      structure is lacking. The aim of this research is to study that structure in the
      self-administered version in a sample of the Spanish population with acquired
      brain injury and memory loss complaints, and to compare that solution with those
      obtained in other studies. PATIENTS AND METHODS: The questionnaire was
      administered to 119 subjects with acquired brain injury with different
      aetiologies (traumatic, vascular, tumours, multiple sclerosis, toxic-metabolic
      and others). RESULTS: The Cronbach's alpha coefficient was 0.88. All the items
      showed adequate discriminatory power, except item 15. No relation was found
      between the total score on the DEX and the age, gender and time elapsed since the
      injury. A negative correlation between total score and level of schooling was
      confirmed. The total score does not follow a normal distribution. The five-factor
      solution accounts for a higher percentage of the total variance than those of
      two, three and four factors (63.76%). CONCLUSIONS: The Spanish version of the DEX
      is an instrument that is valid for evaluating general dysexecutive symptoms in
      subjects with acquired brain injury. The five-factor factorial structure
      (planning, cognitive control, inhibition, social awareness and impulse control)
      offers a greater wealth of information because it measures more aspects of the
      dys-executive pathology and therefore appears to be more useful in the clinical
      setting. It is advisable to use the questionnaire in an early stage of evaluation
      or screening and to use it as a complement to the proxy-reported version.

PMID- 23172091
TI  - [Quality of life following surgical treatment of malignant middle cerebral artery
      infarction].
AB  - INTRODUCTION: Little work has been published on the capacity to adapt to the
      disease of patients with malignant middle cerebral artery infarction who have
      undergone decompressive surgery. The purpose of this study is to analyse the
      final quality of life and the degree of satisfaction of patients and their
      relatives. PATIENTS AND METHODS: We analysed 21 patients one year after their
      operation. The quality of life was evaluated using the Spanish version of the
      Sickness Impact Profile. In order to determine the degree of retrospective
      satisfaction, we asked relatives and patients whether, now that the patient's
      current sequelae are known, they would have still agreed to a decompressive
      craniectomy. RESULTS: The physical sphere is felt to be more disrupted than that
      concerning emotional aspects. There are no differences in the quality of life
      between patients who have the right or the left hemisphere affected. Patients
      with a better functional situation report a better quality of life. Altogether,
      81% of patients said they were satisfied. CONCLUSIONS: Despite the fact that all
      the patients show a loss of quality of life after a decompressive craniectomy,
      most of them seem to be satisfied with the treatment they have received, even in
      cases in which the dominant hemisphere is compromised or in those with a moderate
      severe disability.

PMID- 23172092
TI  - [Value of simultaneous electromyographic recording of the levator palpebrae and
      the orbicularis oculi muscles as an early diagnostic marker for blepharospasm].
AB  - INTRODUCTION: Blinking is usually a spontaneous movement that takes place as a
      consequence of the alternating and antagonistic activity of the orbicularis oculi
      and levator palpebrae superioris muscles. In order to achieve an efficient
      movement, they are regulated by a reciprocal inhibition in such a way that the
      agonistic movement triggers the simultaneous inhibition of the antagonist, and
      vice-versa. Co-contraction is the dysfunction of this mechanism and is a
      significant phenomenon in dystonic disorders, especially in simple movements that
      are not subject to variability, as is the case of blinking. Blepharospasm is the
      most frequent dystonia affecting adults and it is easy to diagnose. In incipient
      processes it may offer some difficulties and can even be mistaken for other
      processes. We evaluate the possibility of an early diagnosis of blepharospasm in
      patients with palpebral hyperfunction with a short time to progression. PATIENTS
      AND METHODS: A prospective evaluation of 23 patients with suspected blepharospasm
      was conducted. Each of them was submitted to a simultaneous electromyographic
      study of the orbicularis oculi and levator palpebrae muscles. RESULTS: The
      presence of co-contraction in any of the blinking movements recorded was related
      with the chances of developing blepharospasm in the following years. None of the
      patients who did not have dystonic blinking presented blepharospasm in the years
      of the follow-up; in contrast, it was developed by all of those who presented it
      on some occasion. CONCLUSIONS: Dystonic blinking was observed in all the patients
      with blepharospasm, and blinking was physiological in those who did not present
      it. Simultaneous electromyographic evaluation of the muscles of the eyelids is a
      simple, sensitive, well-tolerated and particularly specific examination that can
      be used to determine whether a patient will show blepharospasm in an early stage
      of development.

PMID- 23172093
TI  - [Reversible encephalopathy caused by valproic acid in an adolescent with
      idiopathic generalised epilepsy].
AB  - INTRODUCTION: Encephalopathy due to valproic acid (VPA) is a rare complication
      leading to a disorder that affects the patient's mental status to a greater or
      lesser extent and which can be accompanied by a paradoxical worsening of the
      seizures. The diagnosis is obvious when it appears within the context of
      hyperammonemia or a liver pathology, but can be difficult to diagnose if it
      appears in isolation in patients who show no other signs of intoxication due to
      VPA. CASE REPORT: We report the case of an adolescent who suffered idiopathic
      generalised epilepsy and presented sub-acute cognitive impairment and a worsening
      of his pattern of seizures some months after starting treatment with VPA. These
      manifestations were accompanied by a slowing of the baseline electroencephalogram
      (EEG) tracing; no biochemical signs of overdosage or toxicity that could be
      attributed to the drug or any other possible aetiology were observed. Withdrawing
      VPA resulted in a swift improvement in the patient's mental status and in the
      control of his seizures. Likewise, EEG recordings also returned to normal.
      CONCLUSIONS: Encephalopathy due to VPA should be considered in patients who
      present a deterioration of their neurological status, whether associated to an
      aggravation of their seizures or not, despite the absence of any analytical signs
      suggestive of VPA toxicity or overdosage. If liver functioning is not affected,
      withdrawal of the drug will determine the disappearance of the symptoms and will
      also allow confirmation of the diagnosis.

PMID- 23172094
TI  - [Levodopa in the treatment of Parkinson's disease: myths and realties].
AB  - In recent years we have witnessed a growing tendency to opt for the use of
      dopamine agonists (DA) as treatment for Parkinson's disease (PD), with the aim of
      delaying as far as possible the development of fluctuations and dyskinesias. Yet,
      levodopa continues to be the most effective antiparkinson drug and is probably
      the one that improves the greatest number of symptoms of the disease. This
      article reports on the results of a comprehensive review of the literature
      dealing with the benefits and risks of levodopa treatment in patients with PD
      which was conducted by a group of expert neurologists and members of the Spanish
      Neurology Society's Movement Disorder Group. The main conclusion reached in this
      article is that levodopa continues to be the most effective treatment for PD.
      Although the risk and incidence of developing dyskinesias remains at a lower
      level in the group initially treated with DA, the number of patients who develop
      disabling dyskinesias is very low in all the studies and is similar for DA and
      for levodopa. Scores on the quality of life scales are also similar in the two
      groups, which casts some doubt on the impact that these motor complications have
      on the quality of life of patients with PD. In view of these findings, we should
      consider whether there is any real justification for depriving patients of the
      good control of their symptoms offered by levodopa owing to the fear of
      developing dyskinesias or mild motor fluctuations that are not really going to
      have any negative effect on their quality of life. There is also the possibility
      of their developing severe side effects, which are more frequent with the use of
      DA.

PMID- 23172095
TI  - [Curares and timbos, poisons used in the Amazon].
AB  - INTRODUCTION: The natives that dwell along the banks of the Orinoco and Amazon
      rivers have used different poisons from plants for centuries. The study reviews
      the historical and ethnographic aspects of the use of curares and timbos in the
      Amazonian region. DEVELOPMENT: Curare is prepared by boiling the roots, bark and
      stalks of different plants belonging to the Loganiaceae (Strychnos) and
      Menispermaceae families (Chondrodendron, Curarea and Abuta). The curares of the
      eastern Amazon are extracted from different species of Strychnos that contain
      quaternary alkaloids, which act by blocking the neuromuscular junction. They are
      used to hunt wild animals and death comes about due to paralysis of the skeletal
      muscles. The first muscles to be paralysed are those of the eyes, nose and neck,
      and then those in the limbs; the diaphragm is the muscle that takes the longest
      to become paralysed. The earliest chronicles reporting their use were written by
      Fernandez de Oviedo, Cristoval de Acuna, Antonio de Ulloa and Jose Gumilla. La
      Condamine, Humbolt, Waterton and Schomburgk, among others, carried out a number
      of different ethnobotanical studies on curare. The ichthyotoxic poisons from
      plants, which are known as timbos or barbascos, are characterised by their high
      level of solubility, their fast diffusion and their high rate of activity. At
      least 70 plant species are used to poison the fish in the tributaries of the
      Amazon with the aim of make fishing easier. Sapindaceae, Papilionaceae,
      Euphorbiaceae and Theophrastaceae contain ichthyotoxic substances, such as
      rotenone or saponins. CONCLUSIONS: Ethnohistorical and ethnographic accounts show
      that the Amazonian cultures have a deep understanding of the toxic properties of
      curares and timbos.

PMID- 23172096
TI  - [Optic nerve head drusen].

PMID- 23172097
TI  - [Interhemispheric diaschisis: a case of crossed aphasia].

PMID- 23172098
TI  - [Ischemic stroke and splenic infarction].

PMID- 23172099
TI  - [Conjoint analysis in treatments with oral anticoagulants. Reply].

PMID- 23172100
TI  - Bibliometric analysis of theses and dissertations on prematurity in the Capes
      database.
AB  - OBJECTIVES: To perform a bibliometric analysis of theses and dissertations on
      prematurity in the Capes database from 1987 to 2009. METHODS: This is a
      descriptive study that used the bibliometric approach for the production of
      indicators of scientific production. Operationally, the methodology was developed
      in four steps: 1) construction of the theoretical framework; 2) data collection
      sourced from the abstracts of theses and dissertations available in the Capes
      Thesis Database which presented the issue of prematurity in the period 1987 to
      2009; 3) organization, processing and construction of bibliometric indicators; 4)
      analysis and interpretation of results. RESULTS: Increase in the scientific
      literature on prematurity during the period 1987 to 2009; production is
      represented mostly by dissertations; the institution that received prominence was
      the Universidade de Sao Paulo. The studies are directed toward the low birth
      weight and very low birth weight preterm newborn, encompassing the social,
      biological and multifactorial causes of prematurity. CONCLUSIONS: There is a
      qualified, diverse and substantial scientific literature on prematurity developed
      in various graduate programs of higher education institutions in Brazil.

PMID- 23172101
TI  - Low mannose-binding lectin serum levels are associated with reduced kidney graft
      survival.
AB  - Activation of the complement system is initiated by the alternative, the
      classical, or the lectin pathway. As the complement system is involved in the
      pathophysiology of graft rejection after kidney transplantation, we investigated
      the possible role of mannose-binding lectin in kidney transplantation and the
      influence of human leukocyte antigen (HLA) immunization on this process. In a
      prospective study of 544 kidney transplant patients over a follow-up period of 5
      years, low serum levels of this lectin at the time of transplantation were found
      to be significantly associated with decreased 5-year death-censored graft
      survival (hazard ratio 1.68). Subanalysis showed that this association was
      confined to non-HLA-immunized patients (hazard ratio 1.93). The strongest
      association was seen in non-HLA-immunized patients receiving a kidney from a
      deceased donor (hazard ratio 2.93). No significant association with mannose
      binding lectin levels and graft survival were found in HLA-immunized patients.
      Variant MBL2 genotypes causing low mannose-binding lectin serum concentrations
      showed the same association pattern. Our findings demonstrate a clear protective
      role of mannose-binding lectin and thus innate immunity in maintaining kidney
      graft survival, but these are probably overruled by HLA immunization.

PMID- 23172104
TI  - Imbalance between Th17 and Treg cells may play an important role in the
      development of chronic unpredictable mild stress-induced depression in mice.
AB  - BACKGROUND: Recent data suggest that major depression is potentially associated
      with dysregulated cytokine production. However, the roles of T helper (Th) cells
      and their subsets in the development of depression still remain to be determined.
      The present study assessed changes in Th cell subsets and cytokines during the
      development of depression in a mouse model. METHODS: Chronic unpredictable mild
      stress (CUMS) was used to simulate depression behavior in mice. The open field
      test, sucrose preference, and ingestion were used as evaluative indicators of
      depressive behavior. During the CUMS protocol, on days 3, 7, 14, and 21, we
      assessed behavioral changes, cytokine levels in serum or stimulated (CD3/CD28)
      cell culture medium, and mRNA expression (ELISA, RT-PCR), regulatory T (Treg) and
      Th17 subsets in spleen (ex vivo, flow cytometry, RT-PCR), and CD3/rIL-23
      stimulated Th17 cell proliferation (MTT assay). RESULTS: The results showed that
      in the depression model mice, IL-4 mRNA expression and serum levels increased on
      day 7, while no detectable change was observed in IFN-gamma. Notably, a reduced
      proportion of Th17 cells with decreased proliferation capacity was observed at
      later stages, in parallel with a decline in serum IL-23 levels. In contrast, an
      increased Treg cell proportion and increased Foxp3 mRNA expression were observed
      in the mid-stages. Correlation analysis showed that the proportion of Tregs was
      correlated negatively with sucrose preference, while the proliferation of Th17
      cells was notably correlated positively with sucrose preference. Also, an
      increased TGF-beta level was detected in serum and was believed to be a key
      factor responsible for the imbalance between Th17 and Treg cells. Furthermore,
      the sucrose preference in TGF-beta type I receptor blockade mice increased
      considerably, compared with CUMS mice. CONCLUSION: These results indicate that in
      CUMS-induced depression, behavioral changes may closely correlate with the
      imbalance between Th17 and Treg cell subsets, and TGF-beta may be a key
      regulatory cytokine.

PMID- 23172105
TI  - Crimean-Congo hemorrhagic fever nosocomial infection in a immunosuppressed
      patient, Pakistan: case report and virological investigation.
AB  - Crimean-Congo hemorrhagic fever (CCHF) is endemic in the Baluchistan province,
      Pakistan. Sporadic outbreaks of CCHF occur throughout the year especially in
      individuals in contact with infected livestock. Nosocomial transmission remains a
      risk due to difficulties in the diagnosis of CCHF and limited availability of
      facilities for the isolation of suspected patients. Rapid diagnosis of CCHF virus
      infection is required for early management of the disease and to prevent
      transmission. This study describes the case of a 43-year-old surgeon who
      contracted CCHF during a surgical procedure in Quetta, Baluchistan and who was
      transferred to a tertiary care facility at the Aga Khan University Hospital,
      Karachi within 1 week of contracting the infection. Diagnosis of CCHF was made
      using a rapid real-time reverse transcription polymerase chain reaction (RT-PCR)
      assay for CCHF viral RNA. The patient had chronic hepatitis B and hepatitis D
      infection for which he had previously received a liver transplant. He proceeded
      to develop classic hemorrhagic manifestations and succumbed to the infection 14
      days post-onset of disease. There was no further nosocomial transmission of the
      CCHF during the hospital treatment of the surgeon. Early diagnosis of CCHF
      enables rapid engagement of appropriate isolation, barrier nursing and infection
      control measures thus preventing nosocomial transmission of the virus.

PMID- 23172106
TI  - A 'turn-off' emission based chemosensor for HSO4(-)--formation of a hydrogen
      bonded complex.
AB  - Anion sensing behaviour of a quinoline-based derivative has been explored and is
      found to be selective towards HSO(4)(-) over a variety of anions including oxo
      anions. The sensing protocol has been suggested to proceed via a static emission
      quenching process which has further been supported by (1)H NMR, UV-vis and
      theoretical (DFT, TD-DFT) calculations indicating the formation of a hydrogen
      bonded complex between the quinoline part of the receptor and HSO(4)(-).

PMID- 23172107
TI  - Arylation of 2-substituted pyridines via Pd-catalyzed decarboxylative cross
      coupling reactions of 2-picolinic acid.
AB  - The novel palladium-catalyzed decarboxylative cross-coupling reactions of 2
      picolinic acid with aryl and heteroaryl bromides including benzenes,
      naphthalenes, pyridines and quinolines for C-C bond formation have been
      successfully achieved.

PMID- 23172109
TI  - Correlates of efavirenz exposure in Chilean patients affected with human
      immunodeficiency virus reveals a novel association with a polymorphism in the
      constitutive androstane receptor.
AB  - OBJECTIVE: To explore the effect of demographics and single-nucleotide
      polymorphisms in cytochrome P450 (CYP) 2B6, 2A6, UDP-glucuronosyltransferase
      (UGT) 2B7, and the constitutive androstane receptor (CAR) genes on efavirenz
      pharmacokinetics in a Chilean cohort affected with human immunodeficiency virus.
      METHODS: Timed plasma samples obtained throughout the dosing interval were
      analyzed for efavirenz concentrations with liquid chromatography/tandem mass
      spectrometry. DNA from whole-blood samples was used for genetic analysis. Data
      were analyzed using a Mann-Whitney statistical test; furthermore, a Pearson or
      Spearman correlation was used. A multivariate analysis was then conducted using
      multiple linear regression by best subset analysis. RESULTS: Overall 219 patients
      were included, 208 patients had measurable efavirenz levels and available genetic
      samples. The overall median (interquartile range) of efavirenz concentration was
      2.6 (2.1-3.7) mcg/mL. In multivariate regression analysis, CYP2B6 516G>T (P <
      0.0001) and CAR rs2307424 C>T (P = 0.002) were significantly related to efavirenz
      plasma concentrations. CONCLUSION: This novel association between CAR rs2307424
      and efavirenz plasma concentrations now requires validation in other cohorts.

PMID- 23172110
TI  - Magnetic carbon nanostructures: microwave energy-assisted pyrolysis vs.
      conventional pyrolysis.
AB  - Magnetic carbon nanostructures from microwave assisted- and conventional
      pyrolysis processes are compared. Unlike graphitized carbon shells from
      conventional heating, different carbon shell morphologies including nanotubes,
      nanoflakes and amorphous carbon were observed. Crystalline iron and cementite
      were observed in the magnetic core, different from a single cementite phase from
      the conventional process.

PMID- 23172108
TI  - Hypothalamic and other connections with dorsal CA2 area of the mouse hippocampus.
AB  - The CA2 area is an important, although relatively unexplored, component of the
      hippocampus. We used various tracers to provide a comprehensive analysis of CA2
      connections in C57BL/6J mice. Using various adeno-associated viruses that express
      fluorescent proteins, we found a vasopressinergic projection from the
      paraventricular nuclei of the hypothalamus (PVN) to the CA2 as well as a
      projection from pyramidal neurons of the CA2 to the supramammillary nuclei. These
      projections were confirmed by retrograde tracing. As expected, we observed CA2
      afferent projections from neurons in ipsilateral entorhinal cortical layer II as
      well as from bilateral dorsal CA2 and CA3 using retrograde tracers. Additionally,
      we saw CA2 neuronal input from bilateral medial septal nuclei, vertical and
      horizontal limbs of the nucleus of diagonal band of Broca, supramammillary nuclei
      (SUM), and median raphe nucleus. Dorsal CA2 injections of adeno-associated virus
      expressing green fluorescent protein revealed axonal projections primarily to
      dorsal CA1, CA2, and CA3 bilaterally. No projection was detected to the
      entorhinal cortex from the dorsal CA2. These results are consistent with recent
      observations that the dorsal CA2 forms disynaptic connections with the entorhinal
      cortex to influence dynamic memory processing. Mouse dorsal CA2 neurons send
      bilateral projections to the medial and lateral septal nuclei, vertical and
      horizontal limbs of the diagonal band of Broca, and SUM. Novel connections from
      the PVN and to the SUM suggest important regulatory roles for CA2 in mediating
      social and emotional input for memory processing.

PMID- 23172111
TI  - Syntheses, structures and chemical sensing properties of three complexes with
      mixed ligands of carboxylate and bipyridine.
AB  - Three mixed-ligand coordination polymers, [Cu(oda)(2,2'-bipy)](2) (1),
      Ni(2)(oda)(2)(4,4'-bipy).DMF (2), and [{Ni(oda)(H(2)O)(2)}(2)(MU-4,4'
      bipy)].2H(2)O (3) were synthesized and characterized. Complex 1 features a 1D
      chain via intermolecular pi-pi interactions. Complex 2 is a novel 3D microporous
      coordination polymer with 1D polarized channels. Complex 3 forms a 3D network via
      extensive hydrogen bonding interactions. Thermogravimetric analyses have been
      studied. The chemical sensing properties have been investigated in situ by quartz
      crystal microbalance (QCM). Complex 1 has a good sensitivity to toluene,
      complexes 2 and 3 have exceptionally high selectivity and sensitivity to water
      over organic solvents.

PMID- 23172114
TI  - Professor Manuel Jose Barbanoj Rodriguez.

PMID- 23172116
TI  - Characterization of tooth structure and the dentin-enamel zone based on the
      Stokes-Mueller calculation.
AB  - This is the first study of dentin-enamel zone (DEZ) identification with tooth
      structure characterization based on the optical Stokes-Mueller measurement.
      Stokes vectors of a cross-sectional tooth slice were measured using various
      polarization inputs. The direction of the DEZ is different in enamel and dentin
      structures; therefore, the Stokes profiles can specifically characterize the
      structures based on the DEZ. This optical method, using polarimetry, provides a
      useful tool for characterizing tooth.

PMID- 23172117
TI  - Effects of collagen cross-linking on the interlamellar cohesive strength of
      porcine cornea.
AB  - PURPOSE: To determine the interlamellar cohesive strength (ICS) of porcine cornea
      before and after collagen cross-linking using riboflavin and ultraviolet A (UVA)
      irradiation. METHODS: Corneal flaps, 130 MUm thick, were created with a
      microkeratome. Cross-linking was accomplished with 0.1% riboflavin and UVA
      irradiation for 30 minutes (3 mW/cm, 5.4 J/cm) at a distance of 10 mm. Two
      experiments were performed. (1) The maximal ICS between corneal flap and the
      stroma was determined and histological examination was performed. (2) The mean
      stromal ICS was measured. Untreated eyes served as controls in all experiments.
      RESULTS: The mean maximum flap-stroma ICS was 0.088 +/- 0.046 N/mm in the
      experimental group and 0.012 +/- 0.004 N/mm in the control group (P = 0.009). In
      experiment 2, incomplete (2 mm long) corneal flaps were used and the mean stromal
      ICS was 0.750 +/- 0.077 N/mm in the experimental group and 0.338 +/- 0.046 N/mm
      in the control group (P < 0.0001). Histological examination showed an irregular
      ragged separation of the surface in the stromal margin of the cornea with cross
      linking, but a smooth separation surface in the cornea without cross-linking.
      CONCLUSIONS: Collagen cross-linking activated by riboflavin/UVA increases ICS in
      porcine corneas.

PMID- 23172118
TI  - Reply: To PMID 22081155.

PMID- 23172119
TI  - Repeatability of in vivo corneal confocal microscopy to quantify corneal nerve
      morphology.
AB  - PURPOSE: To establish intraobserver and interobserver repeatability, agreement,
      and symmetry of corneal nerve fiber (NF) morphology in healthy subjects using in
      vivo corneal confocal microscopy. METHODS: Nineteen subjects underwent in vivo
      corneal confocal microscopy (Heidelberg Retinal Tomograph III Rostock Cornea
      Module) at baseline and 7 days apart. Bland-Altman plots were generated to assess
      agreement, and the intraclass correlation coefficient and coefficient of
      repeatability were calculated to estimate intraobserver and interobserver
      repeatability for corneal NF density (numbers per square millimeter), nerve
      branch density (NBD; numbers per square millimeter), NF length (millimeters per
      square millimeter), and NF tortuosity coefficient. Symmetry between the right and
      left eyes was also assessed. RESULTS: Intraclass correlation coefficient and
      coefficient of repeatability for intraobserver repeatability were 0.66 to 0.74
      and 0.17 to 0.64, for interobserver repeatability 0.54 to 0.93 and 0.15 to 0.85,
      and for symmetry 0.34 to 0.77 and 0.17 to 0.63, respectively. NBD demonstrated
      low repeatability. CONCLUSIONS: This study demonstrates good repeatability for
      the manual assessment of all major corneal NF parameters with the exception of
      NBD, which highlights the difficulty in defining nerve branches and suggests the
      need for experienced observers or automated image analysis to ensure optimal
      repeatability.

PMID- 23172120
TI  - The effect of anesthetic eye drop instillation on the distribution of corneal
      thickness.
AB  - PURPOSE: To address the effect of topical instillation of oxybuprocaine on the
      relative distribution of corneal thickness (CT) in young healthy subjects.
      METHODS: Prospective study involving 30 eyes of 30 emmetropic subjects (24 +/- 3
      years). Corneal thickness measurements were carried out before and 3 minutes
      after the instillation of oxybuprocaine 4% using slit-scanning corneal topography
      (Orbscan topography system II). No acoustic correction factor was applied. The
      mean of 5 consecutive Orbscan measurements was obtained at the center and 3 mm
      from the visual axis in the temporal, superior, nasal, and inferior
      hemimeridians. RESULTS: No significant mean differences were found at any corneal
      location after anesthesia (P > 0.05). The difference between the baseline values
      obtained of the central, superior, inferior, nasal, and temporal cornea and those
      obtained after anesthesia ranged from -15 to 16 MUm, from -19 to 32 MUm, from -14
      to 24 MUm, from -20 to 33 MUm, and from -31 to 18 MUm, respectively. The maximum
      paracentral CT was never found at the temporal location before anesthesia,
      whereas it was never found at the inferior location after anesthesia. The minimum
      paracentral CT was never found in the superior location after anesthesia.
      CONCLUSIONS: Topical anesthetic eye drops induce CT increases and decreases at
      each corneal location; however, the differences are not significant.
      Nevertheless, a change in the location of the minimum and maximum paracentral
      thickness occurs in some individuals after corneal anesthesia.

PMID- 23172121
TI  - Elastic CNT-polyurethane nanocomposite: synthesis, performance and assessment of
      fragments released during use.
AB  - Intended for use in high performance applications where electrical conductivity
      is required, we developed a CNT-TPU composite. Such a composite can be prepared
      by melt processing (extrusion) on an industrial scale. Due to the known hazard
      upon inhalation of CNTs, we assessed three degradation scenarios that may lead to
      the release of CNTs from the composite: normal use, machining and outdoor
      weathering. Unexpectedly, we find that the relative softness of the material
      actually enhances the embedding of CNTs also in its degradation fragments. A
      release of free CNTs was not detected under any condition using several detection
      methods. However, since machining may induce a high acute dose of human exposure,
      we assessed the cytotoxicity potential of released fragments in the in vitro
      model of precision-cut lung slices, and found no additional toxicity due to the
      presence of CNTs. At very low rates over years, weathering degrades the polymer
      matrix as expected for polyurethanes, thus exposing a network of entangled CNTs.
      In a preliminary risk assessment, we conclude that this material is safe for
      humans in professional and consumer use.

PMID- 23172122
TI  - Phenolic promiscuity in the cell nucleus--epigallocatechingallate (EGCG) and
      theaflavin-3,3'-digallate from green and black tea bind to model cell nuclear
      structures including histone proteins, double stranded DNA and telomeric
      quadruplex DNA.
AB  - Flavanols from tea have been reported to accumulate in the cell nucleus in
      considerable concentrations. The nature of this phenomenon, which could provide
      novel approaches in understanding the well-known beneficial health effects of tea
      phenols, is investigated in this contribution. The interaction between
      epigallocatechin gallate (EGCG) from green tea and a selection of theaflavins
      from black tea with selected cell nuclear structures such as model histone
      proteins, double stranded DNA and quadruplex DNA was investigated using mass
      spectrometry, Circular Dichroism spectroscopy and fluorescent assays. The
      selected polyphenols were shown to display affinity to all of the selected cell
      nuclear structures, thereby demonstrating a degree of unexpected molecular
      promiscuity. Most interestingly theaflavin-digallate was shown to display the
      highest affinity to quadruplex DNA reported for any naturally occurring molecule
      reported so far. This finding has immediate implications in rationalising the
      chemopreventive effect of the tea beverage against cancer and possibly the role
      of tea phenolics as "life span essentials".

PMID- 23172123
TI  - Moisture-swing sorption for carbon dioxide capture from ambient air: a
      thermodynamic analysis.
AB  - An ideal chemical sorbent for carbon dioxide capture from ambient air (air
      capture) must have a number of favourable properties, such as environmentally
      benign behaviour, a high affinity for CO(2) at very low concentration (400 ppm),
      and a low energy cost for regeneration. The last two properties seem
      contradictory, especially for sorbents employing thermal swing adsorption. On the
      other hand, thermodynamic analysis shows that the energy cost of an air capture
      device need only be slightly larger than that of a flue gas scrubber. The
      moisture swing separation process studied in this paper provides a novel approach
      to low cost CO(2) capture from air. The anionic exchange resin sorbent binds
      CO(2) when dry and releases it when wet. A thermodynamic model with coupled phase
      and chemical equilibria is developed to study the complex H(2)O-CO(2)-resin
      system. The moisture swing behaviour is compatible with hydration energies
      changing with the activity of water on the resin surfaces. This activity is in
      turn set by the humidity. The rearrangement of hydration water on the resin upon
      the sorption of a CO(2) molecule is predicted as a function of the humidity and
      temperature. Using water as fuel to drive the moisture swing enables an
      economical, large-scale implementation of air capture. By generating CO(2) with
      low partial pressures, the present technology has implications for in situ CO(2)
      utilizations which require low pressure CO(2) gas rather than liquid CO(2).

PMID- 23172128
TI  - On mite allergy in dogs and humans.

PMID- 23172129
TI  - Nuclear factor of activated T cells 5 deficiency increases the severity of
      neuronal cell death in ischemic injury.
AB  - Nuclear factor of activated T cells 5 (NFAT5) has been implicated in regulating
      several genes that are thought to be neuroprotective in ischemic injury. Because
      of the embryonic lethality of NFAT5 knockout (NFAT5(-/-)) mice, the heterozygous
      (NFAT5(+/-)) mice were used to study the in vivo role of NFAT5 in
      hypoxia/ischemia (H/I) condition. The NFAT5(+/-) mice exhibited more severe
      neurological deficits, larger infarct area and edema formation associated with
      increased aquaporin 4 expressions in the brain. Under in vitro H/I condition,
      increased apoptotic cell death was found in NFAT5(-/-) neurons. Moreover, SMIT, a
      downstream to NFAT5, was upregulated in NFAT5(+/+) neurons, while the SMIT level
      could not be upregulated in NFAT5(-/-) neurons under H/I condition. The elevation
      of reactive oxygen species generation in NFAT5(-/-) neurons under H/I condition
      further confirmed that NFAT5(-/-) neurons were more susceptible to oxidative
      stress. The present study demonstrated that activation of NFAT5 and its
      downstream SMIT induction is important in protecting neurons from ischemia
      induced oxidative stress.

PMID- 23172127
TI  - The MAURO study: baseline characteristics and compliance with guidelines targets.
AB  - BACKGROUND: The Multiple Intervention and Audit in Renal Diseases to Optimize
      Care (MAURO) study was a cluster randomized controlled trial in 22 renal clinics
      which aimed to assess the efficacy of a multimodal quality improvement
      intervention to increase compliance with guideline recommendations for prevention
      of chronic kidney disease (CKD) progression and cardiovascular (CV)
      complications. The trial aimed to test whether this multimodal intervention
      improved adherence to recommended targets for a series of surrogate indicators
      relevant to blood pressure (BP) control, sodium intake, proteinuria,
      dyslipidemia, anemia and calcium-phosphate alterations. The trial also tested
      whether the same intervention slowed CKD progression and prevented CV
      complications in CKD patients. METHOD: Twenty-two renal clinics were randomized
      to 2 arms: an intervention arm applying a multimethod quality improvement
      intervention and a control arm providing standard care. Surrogate indicators were
      measured to evaluate blood pressure (BP) control, sodium intake, proteinuria,
      dyslipidemia, anemia and calcium-phosphate alterations. RESULTS: Notwithstanding
      the fact that the vast majority of patients enrolled in this study (95%) were
      being treated with antihypertensive drugs, BP goals at baseline (specific for
      proteinuria level and diabetes) were met only in 45% of nonproteinuric patients
      and in just 14% and 18% of proteinuric and diabetic patients, respectively. The
      use of diuretics in hypertensive patients was less than what was needed, and
      about 80% of patients showed a salt excretion >100 mmol/24 hours. Total and low
      density lipoprotein cholesterol levels were out of target in over 40% of
      patients, but only about 60% of these were on statins. A large majority of CKD
      patients were obese or overweight. The proportion of smokers was relatively small
      (13%), and 37% of patients had quit smoking, indicating patients' awareness of
      the health risks of smoking. CONCLUSIONS: In our cohort, management of modifiable
      risk factors for CKD progression and CV disease could be substantially improved.

PMID- 23172130
TI  - Hepatitis C virus and nonliver solid organ transplantation.
AB  - : Hepatitis C virus (HCV) infection is common in solid organ allograft recipients
      and is a significant cause of morbidity and mortality after transplantation, so
      effective management will improve outcomes. In this review, we discuss the extent
      of the problem associated with HCV infection in donors and kidney, heart, and
      lung transplant candidates and recipients and recommend follow-up and
      treatment.Patients with end-stage kidney disease without cirrhosis and selected
      patients with early-stage cirrhosis can be considered for kidney transplant
      alone. In HCV-infected kidney allograft recipients, the progression of fibrosis
      should be evaluated serially by Fibroscan or serologic measures of fibrosis.
      Transplantation of kidneys from HCV-positive donors should be restricted to HCV
      positive recipients as it is associated with a reduced time waiting for a graft
      and does not affect posttransplant outcomes. Hepatitis C virus antiviral therapy
      should be considered for all HCV-RNA-positive kidney transplant candidates,
      irrespective of the baseline liver histopathology. Protease inhibitors have yet
      to be fully evaluated in patients with renal dysfunction and in the transplant
      population. As these agents may cause anemia in patients with normal renal
      function, tolerability may be a problem in patients with end-stage kidney
      disease.The impact of HCV infection on survival in heart and lung transplantation
      is unclear. Because of the shortage of organs, few HCV-infected patients are
      accepted for transplantation.Universal use of nucleic acid amplification testing
      (NAT) for the screening of potential organ donors should be reserved to high-risk
      donors. Assays that quantify HCV core antigen may become more cost-effective than
      NAT for the screening of potential organ donors.

PMID- 23172131
TI  - Neurodevelopmental assessment of very low birth weight preterm infants at
      corrected age of 18-24 months by Bayley III scales.
AB  - OBJECTIVE: To evaluate the prevalence of delay and factors associated with
      neurodevelopmental scores in premature infants. METHODS: Cross-sectional study to
      assess the development by Bayley Scales III, including very low birth weight
      preterm infants aged 18 to 24 months who were under follow-up at the outpatient
      clinic for preterm infants. Congenital malformation, genetic syndrome,
      symptomatic congenital infection at birth, deafness, and blindness were excluded.
      Numerical variables were compared by Mann-Whitney or Student t test and
      categorical variables by chi-square or Fisher's exact test. Factors associated
      with developmental scores were analyzed by linear regression, and statistical
      significance level was established at p < 0.05. RESULTS: Out of the 58 children
      included, four (6.9%) presented cognitive delay, four (6.9%) motor, 17 (29.3%)
      language, 16 (27.6%) social-emotional and 22 (37.0%) adaptive-behavior delay. By
      multiple linear regression, the variables: social classes CDE (-13.27; 95%CI: 
      21.23 to -5.31), oxygen dependency at 36 weeks of corrected age (-8.75; 95%CI: 
      17.10 to -0.39) decreased the cognitive developmental score. Periventricular
      leukomalacia decreased the cognitive (-15.21; 95%CI: -27.61 to -2.81), motor (
      10.67; 95%CI:-19.74 to -1.59) and adaptive-behavior scores (-21.52; 95%CI: -35.60
      to -7.44). The female sex was associated with higher motor (10.67; 95%CI: 2.77 to
      12.97), language (15.74; 95%CI: 7.39 to 24.09) and social-emotional developmental
      scores (10.27; 95%CI: 1.08 to 19.46). CONCLUSIONS: Very low birth weight preterm
      infants aged from 18 to 24 months of corrected age presented more frequently
      language, social-emotional and adaptive-behavior delays. The variables: social
      classes CDE, periventricular leukomalacia, bronchopulmonary dysplasia and male
      sex reduced the neurodevelopmental scores.

PMID- 23172132
TI  - An immobilized and reusable Cu(I) catalyst for metal ion-free conjugation of
      ligands to fully deprotected oligonucleotides through click reaction.
AB  - Chelation of Cu(I) ions to an immobilized hydrophilic tris(triazolylmethyl)amine
      chelator on a solid support allowed synthesis of RNA oligonucleotide conjugates
      from completely deprotected alkyne-oligonucleotides. No oligonucleotide strand
      degradation or metal ion contamination was observed. Furthermore, use of the
      immobilized copper(I) ion overcame regioselectivity issues associated with strain
      promoted copper-free azide-alkyne cycloaddition.

PMID- 23172133
TI  - Second harmonic generation reveals matrix alterations during breast tumor
      progression.
AB  - Alteration of the extracellular matrix in tumor stroma influences efficiency of
      cell locomotion away from the primary tumor into surrounding tissues and
      vasculature, thereby affecting metastatic potential. We study matrix changes in
      breast cancer through the use of second harmonic generation (SHG) of collagen in
      order to improve the current understanding of breast tumor stromal development.
      Specifically, we utilize a quantitative analysis of the ratio of forward to
      backward propagating SHG signal (F/B ratio) to monitor collagen throughout ductal
      and lobular carcinoma development. After detection of a significant decrease in
      the F/B ratio of invasive but not in situ ductal carcinoma compared with healthy
      tissue, the collagen F/B ratio is investigated to determine the evolution of
      fibrillar collagen changes throughout tumor progression. Results are compared
      with the progression of lobular carcinoma, whose F/B signature also underwent
      significant evolution during progression, albeit in a different manner, which
      offers insight into varying methods of tissue penetration and collagen
      manipulation between the carcinomas. This research provides insights into trends
      of stromal reorganization throughout breast tumor development.

PMID- 23172138
TI  - Resonant light scattering spectroscopy of gold, silver and gold-silver alloy
      nanoparticles and optical detection in microfluidic channels.
AB  - Dark field resonant light scattering by gold and silver nanoparticles enables the
      detection and spectroscopy of such particles with high sensitivity, down to the
      single-particle level, and can be used to implement miniaturised optical
      detection schemes for chemical and biological analysis. Here, we present a
      straightforward optical spectroscopic methodology for the quantitative
      spectrometric study of resonant light scattering (RLS) by nanoparticles. RLS
      spectroscopy is complementary to UV-visible absorbance measurements, and we apply
      it to the characterisation and comparison of different types of gold, silver and
      gold-silver alloy nanoparticles. The potential of gold and silver particles as
      alternatives for fluorescent probes in certain applications is discussed. RLS
      spectroscopy is shown to be useful for studying analyte-induced gold nanoparticle
      assembly and nanoparticle chemistry, which can induce radical changes in the
      plasmonic resonances responsible for the strong light scattering. Furthermore,
      the feasibility of dark field RLS detection and quantitation of metal
      nanoparticles in microfluidic volumes is demonstrated, opening interesting
      possibilities for the further development of microfluidic detection schemes.

PMID- 23172137
TI  - Laminar and connectional organization of a multisensory cortex.
AB  - The transformation of sensory signals as they pass through cortical circuits has
      been revealed almost exclusively through studies of the primary sensory cortices,
      for which principles of laminar organization, local connectivity, and parallel
      processing have been elucidated. In contrast, almost nothing is known about the
      circuitry or laminar features of multisensory processing in higher order,
      multisensory cortex. Therefore, using the ferret higher order multisensory
      rostral posterior parietal (PPr) cortex, the present investigation employed a
      combination of multichannel recording and neuroanatomical techniques to elucidate
      the laminar basis of multisensory cortical processing. The proportion of
      multisensory neurons, the share of neurons showing multisensory integration, and
      the magnitude of multisensory integration were all found to differ by layer in a
      way that matched the functional or connectional characteristics of the PPr.
      Specifically, the supragranular layers (L2/3) demonstrated among the highest
      proportions of multisensory neurons and the highest incidence of multisensory
      response enhancement, while also receiving the highest levels of extrinsic
      inputs, exhibiting the highest dendritic spine densities, and providing a major
      source of local connectivity. In contrast, layer 6 showed the highest proportion
      of unisensory neurons while receiving the fewest external and local projections
      and exhibiting the lowest dendritic spine densities. Coupled with a lack of input
      from principal thalamic nuclei and a minimal layer 4, these observations indicate
      that this higher level multisensory cortex shows functional and organizational
      modifications from the well-known patterns identified for primary sensory
      cortical regions.

PMID- 23172139
TI  - Inhibition dominates sensory responses in the awake cortex.
AB  - The activity of the cerebral cortex is thought to depend on the precise
      relationship between synaptic excitation and inhibition. In the visual cortex, in
      particular, intracellular measurements have related response selectivity to
      coordinated increases in excitation and inhibition. These measurements, however,
      have all been made during anaesthesia, which strongly influences cortical state
      and therefore sensory processing. The synaptic activity that is evoked by visual
      stimulation during wakefulness is unknown. Here we measured visually evoked
      responses--and the underlying synaptic conductances--in the visual cortex of
      anaesthetized and awake mice. Under anaesthesia, responses could be elicited from
      a large region of visual space and were prolonged. During wakefulness, responses
      were more spatially selective and much briefer. Whole-cell patch-clamp recordings
      of synaptic conductances showed a difference in synaptic inhibition between the
      two conditions. Under anaesthesia, inhibition tracked excitation in amplitude and
      spatial selectivity. By contrast, during wakefulness, inhibition was much
      stronger than excitation and had extremely broad spatial selectivity. We conclude
      that during wakefulness, cortical responses to visual stimulation are dominated
      by synaptic inhibition, restricting the spatial spread and temporal persistence
      of neural activity. These results provide a direct glimpse of synaptic mechanisms
      that control sensory responses in the awake cortex.

PMID- 23172140
TI  - Biochemistry: Another aspect of nature's ingenuity.

PMID- 23172141
TI  - Global convergence in the vulnerability of forests to drought.
AB  - Shifts in rainfall patterns and increasing temperatures associated with climate
      change are likely to cause widespread forest decline in regions where droughts
      are predicted to increase in duration and severity. One primary cause of
      productivity loss and plant mortality during drought is hydraulic failure.
      Drought stress creates trapped gas emboli in the water transport system, which
      reduces the ability of plants to supply water to leaves for photosynthetic gas
      exchange and can ultimately result in desiccation and mortality. At present we
      lack a clear picture of how thresholds to hydraulic failure vary across a broad
      range of species and environments, despite many individual experiments. Here we
      draw together published and unpublished data on the vulnerability of the
      transport system to drought-induced embolism for a large number of woody species,
      with a view to examining the likely consequences of climate change for forest
      biomes. We show that 70% of 226 forest species from 81 sites worldwide operate
      with narrow (<1 megapascal) hydraulic safety margins against injurious levels of
      drought stress and therefore potentially face long-term reductions in
      productivity and survival if temperature and aridity increase as predicted for
      many regions across the globe. Safety margins are largely independent of mean
      annual precipitation, showing that there is global convergence in the
      vulnerability of forests to drought, with all forest biomes equally vulnerable to
      hydraulic failure regardless of their current rainfall environment. These
      findings provide insight into why drought-induced forest decline is occurring not
      only in arid regions but also in wet forests not normally considered at drought
      risk.

PMID- 23172142
TI  - A canonical stability-elasticity relationship verified for one million face
      centred-cubic structures.
AB  - Any thermodynamically stable or metastable phase corresponds to a local minimum
      of a potentially very complicated energy landscape. But however complex the
      crystal might be, this energy landscape is of parabolic shape near its minima.
      Roughly speaking, the depth of this energy well with respect to some reference
      level determines the thermodynamic stability of the system, and the steepness of
      the parabola near its minimum determines the system's elastic properties.
      Although changing alloying elements and their concentrations in a given material
      to enhance certain properties dates back to the Bronze Age, the systematic search
      for desirable properties in metastable atomic configurations at a fixed
      stoichiometry is a very recent tool in materials design. Here we demonstrate,
      using first-principles studies of four binary alloy systems, that the elastic
      properties of face-centred-cubic intermetallic compounds obey certain rules. We
      reach two conclusions based on calculations on a huge subset of the face-centred
      cubic configuration space. First, the stiffness and the heat of formation are
      negatively correlated with a nearly constant Spearman correlation for all
      concentrations. Second, the averaged stiffness of metastable configurations at a
      fixed concentration decays linearly with their distance to the ground-state line
      (the phase diagram of an alloy at zero Kelvin). We hope that our methods will
      help to simplify the quest for new materials with optimal properties from the
      vast configuration space available.

PMID- 23172143
TI  - An alternative route to cyclic terpenes by reductive cyclization in iridoid
      biosynthesis.
AB  - The iridoids comprise a large family of distinctive bicyclic monoterpenes that
      possess a wide range of pharmacological activities, including anticancer, anti
      inflammatory, antifungal and antibacterial activities. Additionally, certain
      iridoids are used as sex pheromones in agriculturally important species of
      aphids, a fact that has underpinned innovative and integrated pest management
      strategies. To harness the biotechnological potential of this natural product
      class, the enzymes involved in the biosynthetic pathway must be elucidated. Here
      we report the discovery of iridoid synthase, a plant-derived enzyme that
      generates the iridoid ring scaffold, as evidenced by biochemical assays, gene
      silencing, co-expression analysis and localization studies. In contrast to all
      known monoterpene cyclases, which use geranyl diphosphate as substrate and invoke
      a cationic intermediate, iridoid synthase uses the linear monoterpene 10
      oxogeranial as substrate and probably couples an initial NAD(P)H-dependent
      reduction step with a subsequent cyclization step via a Diels-Alder cycloaddition
      or a Michael addition. Our results illustrate how a short-chain reductase was
      recruited as cyclase for the production of iridoids in medicinal plants.
      Furthermore, we highlight the prospects of using unrelated reductases to generate
      artificial cyclic scaffolds. Beyond the recognition of an alternative biochemical
      mechanism for the biosynthesis of cyclic terpenes, we anticipate that our work
      will enable the large-scale heterologous production of iridoids in plants and
      microorganisms for agricultural and pharmaceutical applications.

PMID- 23172144
TI  - An early age increase in vacuolar pH limits mitochondrial function and lifespan
      in yeast.
AB  - Mitochondria have a central role in ageing. They are considered to be both a
      target of the ageing process and a contributor to it. Alterations in
      mitochondrial structure and function are evident during ageing in most
      eukaryotes, but how this occurs is poorly understood. Here we identify a
      functional link between the lysosome-like vacuole and mitochondria in
      Saccharomyces cerevisiae, and show that mitochondrial dysfunction in
      replicatively aged yeast arises from altered vacuolar pH. We found that vacuolar
      acidity declines during the early asymmetric divisions of a mother cell, and that
      preventing this decline suppresses mitochondrial dysfunction and extends
      lifespan. Surprisingly, changes in vacuolar pH do not limit mitochondrial
      function by disrupting vacuolar protein degradation, but rather by reducing pH
      dependent amino acid storage in the vacuolar lumen. We also found that calorie
      restriction promotes lifespan extension at least in part by increasing vacuolar
      acidity via conserved nutrient-sensing pathways. Interestingly, although vacuolar
      acidity is reduced in aged mother cells, acidic vacuoles are regenerated in
      newborn daughters, coinciding with daughter cells having a renewed lifespan
      potential. Overall, our results identify vacuolar pH as a critical regulator of
      ageing and mitochondrial function, and outline a potentially conserved mechanism
      by which calorie restriction delays the ageing process. Because the functions of
      the vacuole are highly conserved throughout evolution, we propose that lysosomal
      pH may modulate mitochondrial function and lifespan in other eukaryotic cells.

PMID- 23172145
TI  - Autism-related deficits via dysregulated eIF4E-dependent translational control.
AB  - Hyperconnectivity of neuronal circuits due to increased synaptic protein
      synthesis is thought to cause autism spectrum disorders (ASDs). The mammalian
      target of rapamycin (mTOR) is strongly implicated in ASDs by means of upstream
      signalling; however, downstream regulatory mechanisms are ill-defined. Here we
      show that knockout of the eukaryotic translation initiation factor 4E-binding
      protein 2 (4E-BP2)-an eIF4E repressor downstream of mTOR-or eIF4E overexpression
      leads to increased translation of neuroligins, which are postsynaptic proteins
      that are causally linked to ASDs. Mice that have the gene encoding 4E-BP2
      (Eif4ebp2) knocked out exhibit an increased ratio of excitatory to inhibitory
      synaptic inputs and autistic-like behaviours (that is, social interaction
      deficits, altered communication and repetitive/stereotyped behaviours).
      Pharmacological inhibition of eIF4E activity or normalization of neuroligin 1,
      but not neuroligin 2, protein levels restores the normal excitation/inhibition
      ratio and rectifies the social behaviour deficits. Thus, translational control by
      eIF4E regulates the synthesis of neuroligins, maintaining the excitation-to
      inhibition balance, and its dysregulation engenders ASD-like phenotypes.

PMID- 23172146
TI  - Non-synaptic inhibition between grouped neurons in an olfactory circuit.
AB  - Diverse sensory organs, including mammalian taste buds and insect chemosensory
      sensilla, show a marked compartmentalization of receptor cells; however, the
      functional impact of this organization remains unclear. Here we show that
      compartmentalized Drosophila olfactory receptor neurons (ORNs) communicate with
      each other directly. The sustained response of one ORN is inhibited by the
      transient activation of a neighbouring ORN. Mechanistically, such lateral
      inhibition does not depend on synapses and is probably mediated by ephaptic
      coupling. Moreover, lateral inhibition in the periphery can modulate olfactory
      behaviour. Together, the results show that integration of olfactory information
      can occur via lateral interactions between ORNs. Inhibition of a sustained
      response by a transient response may provide a means of encoding salience.
      Finally, a CO(2)-sensitive ORN in the malaria mosquito Anopheles can also be
      inhibited by excitation of an adjacent ORN, suggesting a broad occurrence of
      lateral inhibition in insects and possible applications in insect control.

PMID- 23172147
TI  - Convergent acoustic field of view in echolocating bats.
AB  - Most echolocating bats exhibit a strong correlation between body size and the
      frequency of maximum energy in their echolocation calls (peak frequency), with
      smaller species using signals of higher frequency than larger ones. Size-signal
      allometry or acoustic detection constraints imposed on wavelength by preferred
      prey size have been used to explain this relationship. Here we propose the
      hypothesis that smaller bats emit higher frequencies to achieve directional sonar
      beams, and that variable beam width is critical for bats. Shorter wavelengths
      relative to the size of the emitter translate into more directional sound beams.
      Therefore, bats that emit their calls through their mouths should show a
      relationship between mouth size and wavelength, driving smaller bats to signals
      of higher frequency. We found that in a flight room mimicking a closed habitat,
      six aerial hawking vespertilionid species (ranging in size from 4 to 21 g, ref.
      5) produced sonar beams of extraordinarily similar shape and volume. Each species
      had a directivity index of 11 +/- 1 dB (a half-amplitude angle of approximately
      37 degrees ) and an on-axis sound level of 108 +/- 4 dB sound pressure level
      referenced to 20 MUPa root mean square at 10 cm. Thus all bats adapted their
      calls to achieve similar acoustic fields of view. We propose that the necessity
      for high directionality has been a key constraint on the evolution of
      echolocation, which explains the relationship between bat size and echolocation
      call frequency. Our results suggest that echolocation is a dynamic system that
      allows different species, regardless of their body size, to converge on optimal
      fields of view in response to habitat and task.

PMID- 23172148
TI  - Olfaction: Intimate neuronal whispers.

PMID- 23172149
TI  - Computational materials science: Substitution with vision.

PMID- 23172150
TI  - Plant ecology: Forests on the brink.

PMID- 23172151
TI  - Increasing heterosexual transmission of HIV-1 subtype C in Inland Central Western
      Brazil.
AB  - The molecular epidemiology of HIV-1 in Brazil is complex and heterogeneous
      because several subtypes co-circulate with some important regional differences.
      This study evaluated HIV-1 subtypes amongst pregnant women living in the
      metropolitan area and in the interior cities from central western Brazil. From
      June 2008 to June 2010, 86.9% of confirmed cases of HIV-1 infection amongst
      pregnant women (172 out of 198 cases) were recruited in Goiania/Goias state. The
      HIV-1 pol gene was sequenced after nested-PCR. HIV-1 subtypes were assigned by
      REGA, phylogenetic, and bootscan analyses. The median age of participants was 26
      years (15-41 years range); 58.7% of participants were diagnosed during prenatal
      care and 51.7% of participants came from >50 interior cities within Goias state.
      Amongst the 131 HIV-1 pol sequences, 64.9% were subtype B, 13.0% were BF1
      recombinant, 11.4% were subtype C, 7.6% were subtype F1, and 2.3% were BC
      recombinant. According to the HIV-1 diagnosis date (1994-2010), a significant
      increase in subtype C and a decrease of BF1 mosaics were observed over time. All
      subtype C patients lived in interior cities where the highest prevalence of
      subtype C outside southern Brazil was observed (18.4%). Phylogenetic analysis
      revealed multiple independent introductions of the Brazilian subtype C clade from
      the southern/southeastern regions of Brazil. The HIV-1 epidemic in women from
      central western Brazil infected by the heterosexual route is characterized by an
      unexpectedly high prevalence of subtype C viruses highly related to those
      circulating in southern/southeastern Brazil. These findings highlight the
      importance of molecular surveillance programs outside large metropolitan regions
      in Brazil.

PMID- 23172152
TI  - An alpha-Keggin polyoxometalate completely constructed from the late transition
      metal Co(II) as poly atom.
AB  - We report a catalytic eight-cobalt-capped alpha-Keggin polyoxoazocobaltite with a
      highly symmetric structure completely constructed from the late transition-metal
      Co(II) as a poly atom, [Co(20)(OH)(24)(MMT)(12)(SO(4))](NO(3))(2).6H(2)O (1)
      (MMT: 2-mercapto-5-methyl-1,3,4-thiadiazole). To the best of our knowledge, this
      is the first homometallic Co(II) magnetic cluster bearing Keggin structure. It
      can serve as a potential catalyst in the styrene polymerization.

PMID- 23172153
TI  - Screening therapeutic EMT blocking agents in a three-dimensional
      microenvironment.
AB  - Epithelial-mesenchymal transition (EMT) plays a critical role in the early stages
      of dissemination of carcinoma leading to metastatic tumors, which are responsible
      for over 90% of all cancer-related deaths. Current therapeutic regimens, however,
      have been ineffective in the cure of metastatic cancer, thus an urgent need
      exists to revisit existing protocols and to improve the efficacy of newly
      developed therapeutics. Strategies based on preventing EMT could potentially
      contribute to improving the outcome of advanced stage cancers. To achieve this
      goal new assays are needed to identify targeted drugs capable of interfering with
      EMT or to revert the mesenchymal-like phenotype of carcinoma to an epithelial
      like state. Current assays are limited to examining the dispersion of carcinoma
      cells in isolation in conventional 2-dimensional (2D) microwell systems, an
      approach that fails to account for the 3-dimensional (3D) environment of the
      tumor or the essential interactions that occur with other nearby cell types in
      the tumor microenvironment. Here we present a microfluidic system that integrates
      tumor cell spheroids in a 3D hydrogel scaffold, in close co-culture with an
      endothelial monolayer. Drug candidates inhibiting receptor activation or signal
      transduction pathways implicated in EMT have been tested using dispersion of A549
      lung adenocarcinoma cell spheroids as a metric of effectiveness. We demonstrate
      significant differences in response to drugs between 2D and 3D, and between
      monoculture and co-culture.

PMID- 23172154
TI  - Type-II nanorod heterostructure formation through one-step cation exchange.
AB  - A novel one-step cation exchange approach has been developed to prepare ZnO
      decorated ZnSe nanorods (ZnSe-ZnO NRs), a prototype type-II semiconductor
      nanoheterostructure. Because of the staggered band offset which promoted
      effective charge separation, the as-synthesized ZnSe-ZnO NRs exhibited remarkable
      photocatalytic activities under visible light illumination, demonstrating their
      promising potentials in relevant photoconversion applications.

PMID- 23172155
TI  - Hydrogenated bilayer wurtzite SiC nanofilms: a two-dimensional bipolar magnetic
      semiconductor material.
AB  - Recently, a new kind of spintronics material, bipolar magnetic semiconductors
      (BMS), has been proposed. The spin polarization of BMS can be conveniently
      controlled by a gate voltage, which makes it very attractive in device
      engineering. Now, the main challenge is finding more BMS materials. In this
      article, we propose that hydrogenated wurtzite SiC nanofilm is a two-dimensional
      BMS material. Its BMS character is very robust under the effect of strain,
      substrate or even a strong electric field. The proposed two-dimensional BMS
      material paves the way to use this promising new material in an integrated
      circuit.

PMID- 23172156
TI  - On the origin of the halo stabilization.
AB  - Monte Carlo simulations show that charge-regulation alone can cause highly
      charged zirconium nanoparticles to adsorb to a similarly charged or neutral
      silica particle and thereby stabilizing the latter. This mechanism, referred to
      as halo stabilization, is quite general and applicable in a range of systems
      provided that pH, van der Waals forces, and dissociation constants of the charge
      regulating particles are properly chosen. In our modeling we see an overall
      attraction at low volume fractions of nanoparticles, while at higher a repulsive
      barrier is created, stabilizing the microparticles and protecting them from
      aggregation. The charge-regulation mechanism also turns the silica surface from
      positively charged, without nanoparticles, to negatively charged in the presence
      of nanoparticles.

PMID- 23172160
TI  - The right timing for shrimp tropomyosins.

PMID- 23172161
TI  - Multilocular adenomyoma of seminal vesicle.

PMID- 23172162
TI  - Happy christmas.

PMID- 23172163
TI  - Surgical pathology and the Simpsons.

PMID- 23172164
TI  - Renal choriocarcinoma: gestational or germ cell origin?
AB  - Choriocarcinoma is a rare, highly malignant trophoblastic tumor with gestational
      or, rarely, germ cell origin. Primary extragenital localization is extremely
      rare. This report describes a choriocarcinoma case clinically mimicking a primary
      renal cell carcinoma with multiplex pulmonary metastases. Differentiation from a
      sarcomatoid renal cell carcinoma with trophoblastic differentiation and
      identification of the exact origin, namely gestational or germ cell origin by
      molecular genetic methods is of great importance as it helps determine the
      prognosis and the most effective therapy of the disease. The Investigator
      Hexaplex ESS Kit was used for DNA polymorphism studies. This showed foreign
      alleles in the tumor DNA that confirmed the presence of paternal DNA and the
      gestational origin of the tumor.

PMID- 23172165
TI  - C-cell hyperplasia and papillary thyroid carcinoma.

PMID- 23172166
TI  - Tissue-protective effect of glutamine on hepatic ischemia-reperfusion injury via
      induction of heme oxygenase-1.
AB  - BACKGROUND/AIMS: Glutamine showed cytoprotective activity in vitro on anoxia
      reoxygenation injury via induction of heme oxygenase-1 (HO-1). We thus
      investigated its in vivo tissue-protective effect in a rat liver ischemia
      reperfusion (I/R) model. METHODS: Before the I/R procedure, animals were treated
      with glutamine. Liver injury was evaluated by serum liver enzymes, histological
      examination and apoptosis detection by transferase-mediated uridine nick end
      labeling staining. Meanwhile, expression and activities of HO-1 were measured by
      Western blot and a biochemical method. Liver blood flow was measured by using a
      laser Doppler flowmeter, and oxidative injury was investigated by the
      thiobarbituric acid-reactive substance (TBARS) assay. The inflammatory cytokine
      monocyte chemotactic protein (MCP)-1 was quantified by ELISA. RESULTS: I/R caused
      a large increase in levels of liver enzymes, remarkably inducing the necrosis and
      apoptosis of liver tissue, which was markedly inhibited by glutamine, during
      which HO-1 was upregulated significantly, and the HO-1 inhibitor zinc
      protoporphyrin nullified the effect of glutamine. Liver blood flow was greatly
      reduced after I/R; however, it was significantly improved by glutamine. Lipid
      peroxidation (TBARS) in liver tissue was largely induced which was significantly
      lowered by glutamine. Similar results were also observed for the production of
      MCP-1. CONCLUSION: Glutamine protected tissue against oxidative injury during rat
      hepatic I/R, by induction of HO-1 to fulfill antioxidative and antiapoptotic
      effects.

PMID- 23172167
TI  - Axillary-axillary interarterial chest loop graft for successful early
      hemodialysis access.
AB  - PURPOSE: Obtaining adequate vascular access in patients undergoing chronic
      hemodialysis therapy can be demanding, particularly for those in whom all
      peripheral venous options have been exhausted. CASE: We present a case of a 46
      year-old woman with a history of complex vascular access for end-stage renal
      failure for whom there was no remaining possibility of venous access and had
      reached a palliative stage. We implanted an emergency loop axillary-axillary
      interarterial early needling graft. Post-operatively, the patient made a quick
      and uneventful recovery, resuming hemodialysis after only six days with no
      interventions necessary up to four months follow-up. To the best of our
      knowledge, this is the first dedicated case report describing the successful
      implantation of an axillary-axillary interarterial chest loop graft to re
      establish access in a patient with exhausted options. CONCLUSION: We recommend
      the use of this technique to surgeons who find themselves in comparable
      situations in the future.

PMID- 23172168
TI  - Does prophylactic anticoagulation reduce the risk of femoral tunneled dialysis
      catheter-related complications.
AB  - PURPOSE: To determine the incidence and predictors of femoral tunneled dialysis
      catheter (TDC)-related complications and whether prophylactic anticoagulation is
      associated with reduced catheter-related deep vein thrombosis (CRT) or prolonged
      patency. METHODS: A retrospective review of femoral TDCs inserted for maintenance
      hemodialysis in patients from two dialysis units that have used two different
      strategies to reduce thrombotic complications. One center routinely considered
      all femoral TDCs for prophylactic anticoagulation, whilst the other restricted
      anticoagulation to TDCs that had required repeated treatment with urokinase locks
      to maintain patency. Survival analyses were performed to establish complication
      rates, identify predictors of complications and assess the effect of prophylactic
      anticoagulation use. RESULTS: Of the 194 femoral TDCs identified, 178 (92%) were
      associated with at least one complication. Approximately three quarters did not
      provide adequate small solute clearance; one half were not in use by three
      months; one quarter had at least one catheter-related infection (2.3 per 1000
      catheter days); and one in ten developed a CRT (1.1 per 1000 catheter days).
      Prophylactic anticoagulation was not associated with significant improvements in
      rates of catheter occlusion, CRT, catheter-related infection or dialysis
      adequacy. A previous ipsilateral femoral TDC was identified as a statistically
      significant predictor of a CRT (adjusted hazard ratio 3.7 [95% confidence
      interval 1.4-9.8]; P=.007). CONCLUSIONS: Femoral TDCs are associated with poor
      patency rates and high complication rates; reusing femoral veins for TDCs should
      be avoided where possible, and this study provides no evidence to support routine
      prophylactic anticoagulation in all patients with femoral TDCs.

PMID- 23172169
TI  - Extravasation and extra vigilance.

PMID- 23172170
TI  - The accuracy of ultrasound volume flow measurements in the complex flow setting
      of a forearm vascular access.
AB  - PURPOSE: Maturation of an arterio-venous fistula (AVF) frequently fails, with low
      post-operative fistula flow as a prognostic marker for this event. As pulsed wave
      Doppler (PWD) is commonly used to assess volume flow, we studied the accuracy of
      this measurement in the setting of a radio-cephalic AVF. METHODS: As in-vivo
      validation of fistula flow measurements is cumbersome, we performed simulations,
      integrating computational fluid dynamics with an ultrasound (US) simulator. Flow
      in the arm was calculated, based on a patient-specific model of the arm
      vasculature pre and post AVF creation. Raw ultrasound signals were subsequently
      simulated, from which Doppler spectra were calculated in both a proximal and a
      distal location. RESULTS: The velocity component in the direction of the PWD-US
      beam (vPWD), in a centered, small, sample volume, can be captured accurately
      using PWD spectrum mean-tracking (maximum bias [mB] 8.1%). However, when deriving
      flow rate from these measurements, a high degree of inaccuracy occurs. First, the
      angle-correction of vPWD towards the velocity along the axis of the vessel is
      largely influenced by the radial velocity components in the complex flow field
      (mB=16.3%). Second, the largest error is introduced when transferring the
      centerline velocity to the cross-sectional mean velocity without any knowledge of
      the flow profile (mB=97.7%). CONCLUSIONS: In the setting of a forearm AVF, flow
      estimates based on PWD are hampered by the complex flow patterns. Overall, flow
      estimation based on centerline measurement, analyzed by mean-tracking of the RF
      spectral estimates, under the assumption of a parabolic flow profile, appeared to
      provide the most reasonable values.

PMID- 23172171
TI  - Venous aneurysms in autogenous hemodialysis fistulas: is there an association
      with venous outflow stenosis.
AB  - PURPOSE: To determine whether patients with venous aneurysms in their
      arteriovenous fistulas (AVFs) have associated venous outflow stenoses. MATERIALS
      AND METHODS: A retrospective study was performed, which included all patients
      presenting with dysfunction and had venous aneurysms in their AVFs. Patient's
      medical records and imaging studies were examined and data collected including
      access characteristics, patient demographics and imaging findings. Data were
      analyzed using Fisher's exact test. RESULTS: A total of 89 patients (58 men, 31
      women; mean age 60) presented for intervention related to access dysfunction with
      incident venous aneurysms over the study period. Of the 89 patients with venous
      aneurysms (mean diameter 2.3 cm) of their AVF's, 69 (78%) patients had an
      associated venous outflow stenosis. The stenoses were present most commonly in
      the outflow cephalic vein (57%), followed by the cephalic arch (20%),
      brachiocephalic vein (10%) and subclavian vein (6%). Outflow stenoses in AVFs
      with venous aneurysms were observed in 87% of brachiocephalic AVFs, 60% of
      radiocephalic AVFs and 80% of brachiobasilic AVFs. Brachiocephalic AVFs with
      venous aneurysms were significantly more likely to have an associated outflow
      stenosis than radiocephalic AVFs with venous aneurysms (P=0.007). AVFs with
      outflow stenosis were on average 1502 days old while AVFs without outflow
      stenosis were on average 2351 days old, which was a statistically significant
      difference (P=0.031). No statistically significant differences were observed for
      sex and side of the fistula. CONCLUSIONS: Outflow stenosis was observed to be
      associated with venous aneurysms in AVFs with a more statistically significant
      association in brachiocephalic AVFs compared to other AVFs.

PMID- 23172173
TI  - Early outcomes of the intraluminal flow guard device for secondary renal access.
AB  - PURPOSE: The Flixene Intraluminal Flow Guard (IFG) is a novel arteriovenous graft
      for use in complex renal access patients. The IFG is a PTFE graft with a covered
      nitinol stent at the venous end implanted into the axillary vein rather than
      anastomosed. The purported benefits are improved hemodynamic flow in the vein
      with reduced neointimal hyperplasia. Our primary aim was to assess its early
      patency and complications. Our center is the first to publish early outcomes.
      METHODS: All patients on whom we would have otherwise performed a standard
      brachial-axillary graft from April to November 2011 were instead given an IFG
      graft if they were suitable and consented. The only exclusion criteria was an
      axillary vein size under 5.5 mm as this would not accommodate the intraluminal
      stent graft. Data were collected prospectively and follow-up was identical to our
      usual graft surveillance. RESULTS: A total of 12 patients (mean age 64, mean
      follow-up 393 days) had IFG grafts implanted during the study period. There were
      no exclusions and all patients consented. All patients were having secondary
      access following previous failed fistulae or grafts and no patient had an
      autogenous hemodialysis option. On average each patient had already had 1.1
      previous ipsilateral access procedures. Mean operating time was 109 minutes.
      Functional patency at one year was 65.6%, with a mean functional patency of 162
      days. There was only one early complication (wound hematoma) and one graft
      infection requiring explantation. CONCLUSIONS: The IFG device provides an
      alternative to standard brachial-axillary grafts and brings similar early patency
      and complication profile. Continued monitoring of outcomes, however, is required
      to determine long-term results.

PMID- 23172172
TI  - A multi-center, dose-escalation study of human type I pancreatic elastase (PRT
      201) administered after arteriovenous fistula creation.
AB  - PURPOSE: To explore the safety and efficacy of PRT-201. METHODS: Randomized,
      double-blind, placebo-controlled, single-dose escalation study of PRT-201 (0.0033
      to 9 mg) applied after arteriovenous fistula (AVF) creation. Participants were
      followed for one year. The primary outcome measure was safety. Efficacy measures
      were the proportion with intra-operative increases in AVF outflow vein diameter
      or blood flow >=25% (primary), changes in outflow vein diameter and blood flow,
      AVF maturation and lumen stenosis by ultrasound criteria and AVF patency.
      RESULTS: The adverse events in the PRT-201 group (n=45) were similar to those in
      the placebo group (n=21). There were no differences in the proportion with >=25%
      increase in vein diameter or blood flow, successful maturation or lumen stenosis.
      There was no statistically significant difference in primary patency between the
      dose groups (placebo n=21, Low Dose n=16, Medium Dose n=17 and High Dose n=12).
      In a subgroup analysis that excluded three participants with early surgical
      failures, the hazard ratio (HR) for primary patency loss of Low Dose compared
      with placebo was 0.38 (95% CI 0.10-1.41, P=0.15). In a Cox model, Low Dose (HR
      0.27, 95% CI 0.04-0.79, P=0.09), white race (HR 0.17, 95% CI 0.03-0.79, P=0.02),
      and age <65 years (HR 0.25, CI 0.05-1.15, P=0.08) were associated (P<0.10) with a
      decreased risk of primary patency loss. CONCLUSIONS: PRT-201 was not different
      from placebo for safety or efficacy measures. There was a suggestion for improved
      AVF primary patency with Low Dose PRT-201 that is now being studied in a larger
      clinical trial.

PMID- 23172174
TI  - Subclavian central venous catheters and ultrasound guidance: policy vs practice.
AB  - PURPOSE: Policy statements recommend the use of ultrasound guidance (USG) to
      improve patient safety during placement of central venous catheters (CVCs).
      Studies have conclusively demonstrated greater success rates and fewer
      complications with the use of USG in catheter placement using the internal
      jugular vein approach. Data supporting the use of USG for the subclavian vein
      (SCV) approach, however, have been less conclusive, and USG for SCV cannulation
      is rarely used in clinical practice. We compared USG placement versus anatomic
      placement during subclavian insertion of a CVC. METHODS: A prospective randomized
      study was performed in March 2010 using a simulation model. RESULTS: Ultrasound
      guidance did not provide a statistically significant benefit for successful
      cannulation of the SCV (93.3% with USG and 100% without; P=0.15 or 2) or for rate
      of inadvertent arterial puncture (3.3% with USG and 0% without; P=0.31).
      CONCLUSIONS: The use of USG to access the SCV utilizing a task trainer did not
      improve time to cannulation or success rates. Further study is required to
      delineate why USG for SCV cannulation has not been widely adopted in clinical
      practice.

PMID- 23172175
TI  - Accurate measurement of small airways on low-dose thoracic CT scans in smokers.
AB  - BACKGROUND: Partial volume averaging and tilt relative to the scan plane on
      transverse images limit the accuracy of airway wall thickness measurements on CT
      scan, confounding assessment of the relationship between airway remodeling and
      clinical status in COPD. The purpose of this study was to assess the effect of
      partial volume averaging and tilt corrections on airway wall thickness
      measurement accuracy and on relationships between airway wall thickening and
      clinical status in COPD. METHODS: Airway wall thickness measurements in 80 heavy
      smokers were obtained on transverse images from low-dose CT scan using the open
      source program Airway Inspector. Measurements were corrected for partial volume
      averaging and tilt effects using an attenuation- and geometry-based algorithm and
      compared with functional status. RESULTS: The algorithm reduced wall thickness
      measurements of smaller airways to a greater degree than larger airways,
      increasing the overall range. When restricted to analyses of airways with an
      inner diameter < 3.0 mm, for a theoretical airway of 2.0 mm inner diameter, the
      wall thickness decreased from 1.07 +/- 0.07 to 0.29 +/- 0.10 mm, and the square
      root of the wall area decreased from 3.34 +/- 0.15 to 1.58 +/- 0.29 mm,
      comparable to histologic measurement studies. Corrected measurements had higher
      correlation with FEV1, differed more between BMI, airflow obstruction, dyspnea,
      and exercise capacity (BODE) index scores, and explained a greater proportion of
      FEV1 variability in multivariate models. CONCLUSIONS: Correcting for partial
      volume averaging improves accuracy of airway wall thickness estimation, allowing
      direct measurement of the small airways to better define their role in COPD.

PMID- 23172178
TI  - How resilient is your country?

PMID- 23172177
TI  - Efferent projections of neuropeptide Y-expressing neurons of the dorsomedial
      hypothalamus in chronic hyperphagic models.
AB  - The dorsomedial hypothalamus (DMH) has long been implicated in feeding behavior
      and thermogenesis. The DMH contains orexigenic neuropeptide Y (NPY) neurons, but
      the role of these neurons in the control of energy homeostasis is not well
      understood. NPY expression in the DMH is low under normal conditions in adult
      rodents but is significantly increased during chronic hyperphagic conditions such
      as lactation and diet-induced obesity (DIO). To understand better the role of DMH
      NPY neurons, we characterized the efferent projections of DMH-NPY neurons using
      the anterograde tracer biotinylated dextran amine (BDA) in lactating rats and DIO
      mice. In both models, BDA- and NPY-colabeled fibers were limited mainly to the
      hypothalamus, including the paraventricular nucleus of the hypothalamus (PVH),
      lateral hypothalamus/perifornical area (LH/PFA), and anteroventral
      periventricular nucleus (AVPV). Specifically in lactating rats, BDA-and NPY
      colabeled axonal swellings were in close apposition to cocaine- and amphetamine
      regulated transcript (CART)-expressing neurons in the PVH and AVPV. Although the
      DMH neurons project to the rostral raphe pallidus (rRPa), these projections did
      not contain NPY immunoreactivity in either the lactating rat or the DIO mouse.
      Instead, the majority of BDA-labeled fibers in the rRPa were orexin positive.
      Furthermore, DMH-NPY projections were not observed within the nucleus of the
      solitary tract (NTS), another brainstem site critical for the regulation of
      sympathetic outflow. The present data suggest that NPY expression in the DMH
      during chronic hyperphagic conditions plays important roles in feeding behavior
      and thermogenesis by modulating neuronal functions within the hypothalamus, but
      not in the brainstem.

PMID- 23172190
TI  - Truant particles turn the screw on supersymmetry.

PMID- 23172189
TI  - Drug-pollution law all washed up.

PMID- 23172191
TI  - Hunt for life under Antarctic ice heats up.

PMID- 23172192
TI  - Fresh start for global disease fund.

PMID- 23172193
TI  - Lab astrophysics aims for the stars.

PMID- 23172195
TI  - Private labs caught in budget crunch.

PMID- 23172196
TI  - The science of cities: Life in the concrete jungle.

PMID- 23172197
TI  - Chemical biology: DNA's new alphabet.

PMID- 23172198
TI  - Physics: Make nanotechnology research open-source.

PMID- 23172199
TI  - Physics: Let US physics commit to collaboration.

PMID- 23172204
TI  - Hurricane Sandy: Flood defence for financial hubs.

PMID- 23172205
TI  - Tropical forests: Tightening up on tree carbon estimates.

PMID- 23172206
TI  - Research landscape: Global science can bolster diplomacy.

PMID- 23172207
TI  - Insomnia: Medicalization of sleep may be needed.

PMID- 23172208
TI  - African spiny mouse: Real skin shedding meets mythology.

PMID- 23172209
TI  - Materials science: Synchronized tumbling particles.

PMID- 23172210
TI  - Physical chemistry: Water's response to the fear of water.

PMID- 23172212
TI  - Reproductive biology: Stem cells bear eggs.

PMID- 23172213
TI  - Hippocampal-cortical interaction during periods of subcortical silence.
AB  - Hippocampal ripples, episodic high-frequency field-potential oscillations
      primarily occurring during sleep and calmness, have been described in mice, rats,
      rabbits, monkeys and humans, and so far they have been associated with retention
      of previously acquired awake experience. Although hippocampal ripples have been
      studied in detail using neurophysiological methods, the global effects of ripples
      on the entire brain remain elusive, primarily owing to a lack of methodologies
      permitting concurrent hippocampal recordings and whole-brain activity mapping. By
      combining electrophysiological recordings in hippocampus with ripple-triggered
      functional magnetic resonance imaging, here we show that most of the cerebral
      cortex is selectively activated during the ripples, whereas most diencephalic,
      midbrain and brainstem regions are strongly and consistently inhibited. Analysis
      of regional temporal response patterns indicates that thalamic activity
      suppression precedes the hippocampal population burst, which itself is temporally
      bounded by massive activations of association and primary cortical areas. These
      findings suggest that during off-line memory consolidation, synergistic
      thalamocortical activity may be orchestrating a privileged interaction state
      between hippocampus and cortex by silencing the output of subcortical centres
      involved in sensory processing or potentially mediating procedural learning. Such
      a mechanism would cause minimal interference, enabling consolidation of
      hippocampus-dependent memory.

PMID- 23172214
TI  - Albedo and atmospheric constraints of dwarf planet Makemake from a stellar
      occultation.
AB  - Pluto and Eris are icy dwarf planets with nearly identical sizes, comparable
      densities and similar surface compositions as revealed by spectroscopic studies.
      Pluto possesses an atmosphere whereas Eris does not; the difference probably
      arises from their differing distances from the Sun, and explains their different
      albedos. Makemake is another icy dwarf planet with a spectrum similar to Eris and
      Pluto, and is currently at a distance to the Sun intermediate between the two.
      Although Makemake's size (1,420 +/- 60 km) and albedo are roughly known, there
      has been no constraint on its density and there were expectations that it could
      have a Pluto-like atmosphere. Here we report the results from a stellar
      occultation by Makemake on 2011 April 23. Our preferred solution that fits the
      occultation chords corresponds to a body with projected axes of 1,430 +/- 9 km
      (1sigma) and 1,502 +/- 45 km, implying a V-band geometric albedo p(V) = 0.77 +/-
      0.03. This albedo is larger than that of Pluto, but smaller than that of Eris.
      The disappearances and reappearances of the star were abrupt, showing that
      Makemake has no global Pluto-like atmosphere at an upper limit of 4-12 nanobar
      (1sigma) for the surface pressure, although a localized atmosphere is possible. A
      density of 1.7 +/- 0.3 g cm(-3) is inferred from the data.

PMID- 23172215
TI  - Linking synchronization to self-assembly using magnetic Janus colloids.
AB  - Synchronization occurs widely in the natural and technological worlds, from the
      rhythm of applause and neuron firing to the quantum mechanics of coupled
      Josephson junctions, but has not been used to produce new spatial structures. Our
      understanding of self-assembly has evolved independently in the fields of
      chemistry and materials, and with a few notable exceptions has focused on
      equilibrium rather than dynamical systems. Here we combine these two phenomena to
      create synchronization-selected microtubes of Janus colloids, micron-sized
      spherical particles with different surface chemistry on their opposing
      hemispheres, which we study using imaging and computer simulation. A thin nickel
      film coats one hemisphere of each silica particle to generate a discoid magnetic
      symmetry, such that in a precessing magnetic field its dynamics retain crucial
      phase freedom. Synchronizing their motion, these Janus spheres self-organize into
      micrometre-scale tubes in which the constituent particles rotate and oscillate
      continuously. In addition, the microtube must be tidally locked to the particles,
      that is, the particles must maintain their orientation within the rotating
      microtube. This requirement leads to a synchronization-induced structural
      transition that offers various applications based on the potential to form,
      disintegrate and fine-tune self-assembled in-motion structures in situ.
      Furthermore, it offers a generalizable method of controlling structure using
      dynamic synchronization criteria rather than static energy minimization, and of
      designing new field-driven microscale devices in which components do not
      slavishly follow the external field.

PMID- 23172216
TI  - Water structural transformation at molecular hydrophobic interfaces.
AB  - Hydrophobic hydration is considered to have a key role in biological processes
      ranging from membrane formation to protein folding and ligand binding.
      Historically, hydrophobic hydration shells were thought to resemble solid
      clathrate hydrates, with solutes surrounded by polyhedral cages composed of
      tetrahedrally hydrogen-bonded water molecules. But more recent experimental and
      theoretical studies have challenged this view and emphasized the importance of
      the length scales involved. Here we report combined polarized, isotopic and
      temperature-dependent Raman scattering measurements with multivariate curve
      resolution (Raman-MCR) that explore hydrophobic hydration by mapping the
      vibrational spectroscopic features arising from the hydrophobic hydration shells
      of linear alcohols ranging from methanol to heptanol. Our data, covering the
      entire 0-100  degrees C temperature range, show clear evidence that at low
      temperatures the hydration shells have a hydrophobically enhanced water structure
      with greater tetrahedral order and fewer weak hydrogen bonds than the surrounding
      bulk water. This structure disappears with increasing temperature and is then,
      for hydrophobic chains longer than ~1 nm, replaced by a more disordered structure
      with weaker hydrogen bonds than bulk water. These observations support our
      current understanding of hydrophobic hydration, including the thermally induced
      water structural transformation that is suggestive of the hydrophobic crossover
      predicted to occur at lengths of ~1 nm (refs 5, 9, 10, 14).

PMID- 23172222
TI  - The Escherichia coli toxin MqsR destabilizes the transcriptional repression
      complex formed between the antitoxin MqsA and the mqsRA operon promoter.
AB  - Bacterial biofilms are complex communities of cells containing an increased
      prevalence of dormant cells known as persisters, which are characterized by an up
      regulation of genes known as toxin-antitoxin (TA) modules. The association of
      toxins with their cognate antitoxins neutralizes toxin activity, allowing for
      normal cell growth. Additionally, protein antitoxins bind their own promoters and
      repress transcription, whereas the toxins serve as co-repressors. Recently, TA
      pairs have been shown to regulate their own transcription through a phenomenon
      known as conditional cooperativity, where the TA complexes bind operator DNA and
      repress transcription only when present in the proper stoichiometric amounts. The
      most differentially up-regulated gene in persister cells is mqsR, a gene that,
      with the antitoxin mqsA, constitutes a TA module. Here, we reveal that, unlike
      other TA systems, MqsR is not a transcription co-repressor but instead functions
      to destabilize the MqsA-DNA complex. We further show that DNA binding is not
      regulated by conditional cooperativity. Finally, using biophysical studies, we
      show that complex formation between MqsR and MqsA results in an exceptionally
      stable interaction, resulting in a subnanomolar dissociation constant that is
      similar to that observed between MqsA and DNA. In combination with
      crystallographic studies, this work reveals that MqsA binding to DNA and MqsR is
      mutually exclusive. To our knowledge, this is the first TA system in which the
      toxin does not function as a transcriptional co-repressor, but instead functions
      to destabilize the antitoxin-operator complex under all conditions, and thus
      defines another unique feature of the mqsRA TA module.

PMID- 23172223
TI  - Melanoma antigen-A11 (MAGE-A11) enhances transcriptional activity by linking
      androgen receptor dimers.
AB  - Prostate cancer growth and progression depend on androgen receptor (AR) signaling
      through transcriptional mechanisms that require interactions with coregulatory
      proteins, one of which is the primate-specific steroid receptor coregulator
      melanoma antigen-A11 (MAGE-A11). In this report, we provide evidence how
      increased expression of MAGE-A11 during prostate cancer progression enhances AR
      signaling and prostate cancer growth. MAGE-A11 protein levels were highest in
      castration-recurrent prostate cancer. The cyclic AMP-induced increase in androgen
      dependent and androgen-independent AR transcriptional activity correlated with an
      increase in MAGE-A11 and was inhibited by silencing MAGE-A11 expression. MAGE-A11
      mediated synergistic AR transcriptional activity in LAPC-4 prostate cancer cells.
      The ability of MAGE-A11 to rescue transcriptional activity of complementary
      inactive AR mutants and promote coimmunoprecipitation between unlike forms of AR
      suggests that MAGE-A11 links transcriptionally active AR dimers. A model for the
      AR.MAGE-A11 multidimeric complex is proposed in which one AR FXXLF motif of the
      AR dimer engages in the androgen-dependent AR NH(2)- and carboxyl-terminal
      interaction, whereas the second FXXLF motif region of the AR dimer interacts with
      dimeric MAGE-A11. The AR.MAGE-A11 multidimeric complex accounts for the dual
      functions of the AR FXXLF motif in the androgen-dependent AR NH(2)- and carboxyl
      terminal interaction and binding MAGE-A11 and for synergy between reported AR
      splice variants and full-length AR. We conclude that the increased expression of
      MAGE-A11 in castration-recurrent prostate cancer, which is enhanced by cyclic AMP
      signaling, increases AR-dependent growth of prostate cancer by MAGE-A11 forming a
      molecular bridge between transcriptionally active AR dimers.

PMID- 23172224
TI  - The neuroendocrine protein 7B2 suppresses the aggregation of neurodegenerative
      disease-related proteins.
AB  - Neurodegenerative diseases such as Alzheimer (AD) and Parkinson (PD) are
      characterized by abnormal aggregation of misfolded beta-sheet-rich proteins,
      including amyloid-beta (Abeta)-derived peptides and tau in AD and alpha-synuclein
      in PD. Correct folding and assembly of these proteins are controlled by
      ubiquitously expressed molecular chaperones; however, our understanding of neuron
      specific chaperones and their involvement in the pathogenesis of
      neurodegenerative diseases is limited. We here describe novel chaperone-like
      functions for the secretory protein 7B2, which is widely expressed in neuronal
      and endocrine tissues. In in vitro experiments, 7B2 efficiently prevented
      fibrillation and formation of Abeta(1-42), Abeta(1-40), and alpha-synuclein
      aggregates at a molar ratio of 1:10. In cell culture experiments, inclusion of
      recombinant 7B2, either in the medium of Neuro-2A cells or intracellularly via
      adenoviral 7B2 overexpression, blocked the neurocytotoxic effect of Abeta(1-42)
      and significantly increased cell viability. Conversely, knockdown of 7B2 by RNAi
      increased Abeta(1-42)-induced cytotoxicity. In the brains of APP/PSEN1 mice, a
      model of AD amyloidosis, immunoreactive 7B2 co-localized with aggregation-prone
      proteins and their respective aggregates. Furthermore, in the hippocampus and
      substantia nigra of human AD- and PD-affected brains, 7B2 was highly co-localized
      with Abeta plaques and alpha-synuclein deposits, strongly suggesting
      physiological association. Our data provide insight into novel functions of 7B2
      and establish this neural protein as an anti-aggregation chaperone associated
      with neurodegenerative disease.

PMID- 23172225
TI  - Neuronal Per Arnt Sim (PAS) domain protein 4 (NPAS4) regulates neurite outgrowth
      and phosphorylation of synapsin I.
AB  - Neuronal Per Arnt Sim domain protein 4 (NPAS4), a brain-specific basic helix-loop
      helix transcription factor, has recently been shown to regulate the development
      of the GABAergic inhibitory synapses and transcription program for contextual
      memory formation in the hippocampus. We previously reported that chronic social
      isolation or restriction stress in mice resulted in an impairment in memory and
      emotional behavior, which was associated with a decrease in Npas4 mRNA levels. In
      this study, we investigated the role of NPAS4 in neuronal function in vitro and
      in vivo. Differentiation medium-induced neurite outgrowth was inhibited in Npas4
      knockdown Neuro2a cells, whereas overexpression of NPAS4 accelerated the neurite
      outgrowth in Neuro2a cells. Furthermore, depolarization-induced neurite outgrowth
      was abolished in Npas4 KO hippocampal neurons. NPAS4 overexpression increased
      cyclin-dependent kinase 5 (CDK5)-dependent synapsin I phosphorylation in Neuro2a
      cells and primary cultured hippocampal neurons. A CDK5 inhibitor, roscovitine,
      inhibited the neurite outgrowth and the increase in phosphorylated synapsin I (p
      SYN I) levels in Npas4-overexpressed Neuro2a cells. Interaction of NPAS4 with
      promoters of Cdk5 and NeuN genes was demonstrated by a chromatin
      immunoprecipitation assay. In an in vivo study, pentylenetetrazole-induced
      convulsions in mice resulted in an increase in NPAS4 and p-SYN I levels in the
      prefrontal cortex of wild-type mice, although no changes in p-SYN I levels were
      observed in Npas4 knock-out mice. These results suggest that NPAS4 plays an
      important role in the structural and functional plasticity of neurons.

PMID- 23172226
TI  - Lysine 63-linked ubiquitination modulates mixed lineage kinase-3 interaction with
      JIP1 scaffold protein in cytokine-induced pancreatic beta cell death.
AB  - The mixed lineage kinase MLK3 plays a crucial role in compromising mitochondrial
      integrity and functions as a proapoptotic competence factor in the early stages
      of cytokine-induced pancreatic beta cell death. In an effort to identify
      mechanisms that regulate MLK3 activity in beta cells, we discovered that IL-1beta
      stimulates Lys-63-linked ubiquitination of MLK3 via a conserved, TRAF6-binding
      peptapeptide motif in the catalytic domain of the kinase. TRAF6-mediated
      ubiquitination was required for dissociation of inactive monomeric MLK3 from the
      scaffold protein IB1/JIP1, facilitating the subsequent dimerization,
      autophosphorylation, and catalytic activation of MLK3. Inability to ubiquitinate
      MLK3, or the presence of A20, an upstream Lys-63-linked deubiquitinase, strongly
      curtailed the ability of MLK3 to affect the proapoptotic translocation of BAX in
      cytokine-stimulated pancreatic beta cells, an early step in the progression
      toward beta cell death. These studies suggest a novel mechanism for MLK3
      activation and provide new clues for therapeutic intervention in promoting beta
      cell survival.

PMID- 23172227
TI  - Murine hyaluronidase 2 deficiency results in extracellular hyaluronan
      accumulation and severe cardiopulmonary dysfunction.
AB  - Hyaluronidase (HYAL) 2 is a membrane-anchored protein that is proposed to
      hydrolyze hyaluronan (HA) to smaller fragments that are internalized for
      breakdown. Initial studies of a Hyal2 knock-out (KO) mouse revealed a mild
      phenotype with high serum HA, supporting a role for HYAL2 in HA breakdown. We now
      describe a severe cardiac phenotype, deemed acute, in 54% of Hyal2 KO mice on an
      outbred background; Hyal2 KO mice without the severe cardiac phenotype were
      designated non-acute. Histological studies of the heart revealed that the valves
      of all Hyal2 KO mice were expanded and the extracellular matrix was disorganized.
      HA was detected throughout the expanded valves, and electron microscopy confirmed
      that the accumulating material, presumed to be HA, was extracellular. Both acute
      and non-acute Hyal2 KO mice also exhibited increased HA in the interstitial
      extracellular matrix of atrial cardiomyocytes compared with control mice.
      Consistent with the changes in heart structure, upper ventricular cardiomyocytes
      in acute Hyal2 KO mice demonstrated significant hypertrophy compared with non
      acute KO and control mice. When the lungs were examined, evidence of severe
      fibrosis was detected in acute Hyal2 KO mice but not in non-acute Hyal2 KO or
      control mice. Total serum and heart HA levels, as well as size, were increased in
      acute and non-acute Hyal2 KO mice compared with control mice. These findings
      indicate that HYAL2 is essential for the breakdown of extracellular HA. In its
      absence, extracellular HA accumulates and, in some cases, can lead to
      cardiopulmonary dysfunction. Alterations in HYAL2 function should be considered
      as a potential contributor to cardiac pathologies in humans.

PMID- 23172228
TI  - The C-terminal peptide of chondroadherin modulates cellular activity by
      selectively binding to heparan sulfate chains.
AB  - Chondroadherin, a leucine-rich repeat family member, contains a very C-terminal
      sequence CKFPTKRSKKAGRH(359), now shown to bind to heparin with a K(D) of 13 MUm.
      This observation led us to investigate whether chondroadherin interacts via this
      C-terminal heparin-binding domain with glycosaminoglycan chains of proteoglycans
      at the cell surface. Cells were shown to bind this heparin-binding peptide in
      FACS analysis, and the interaction was shown to be with glycosaminoglycans
      because it was abolished when sulfation was inhibited by chlorate treatment of
      the cells. In separate experiments, heparin and heparan sulfate inhibited the
      peptide interaction in a dose-dependent manner. Using a human chondrosarcoma and
      a murine osteoblast cell line, heparan sulfate proteoglycans were identified as
      the cell surface receptors involved in the binding. Different binding syndecans
      were identified in the two different cell lines, indicating that the same protein
      core of a proteoglycan may have structural and functional differences in the
      attached heparan sulfate chains. Upon binding to coated peptide, cells spread,
      demonstrating engagement of the cytoskeleton, but no focal adhesion complex was
      formed. The number of cells adhering via their beta(1) integrin receptor to
      collagen type II or chondroadherin was profoundly and rapidly enhanced by the
      addition of the heparin-binding peptide. The peptide added to the cells caused
      ERK phosphorylation, showing that it triggered intracellular signaling. The
      results show that heparan sulfate chains differ between various members of the
      proteoglycan families on a given cell, but also differ between the same
      proteoglycan on different cells with a potential for differential regulation of
      cellular activities.

PMID- 23172230
TI  - Case of Reye's syndrome accompanied by hemolytic anemia and cardiac injury after
      cytomegalovirus infection.
AB  - A 6-month-old girl with active human cytomegalovirus (HCMV) infection developed
      Reye's syndrome after vaccination. She suffered from uncommon complications of
      HCMV infection, including Coombs-negative hemolytic anemia and cardiac injury,
      but recovered after the appropriate treatment with prompt ganciclovir and
      symptomatic support. However, the patient died later as a result of a viral upper
      respiratory tract infection, which aggravated the primary disease. This case
      suggests that HCMV infection might be a causative agent of Reye's syndrome.

PMID- 23172231
TI  - Cholesterol--a biological compound as a building block in bionanotechnology.
AB  - Cholesterol is a molecule with many tasks in nature but also a long history in
      science. This feature article highlights the contribution of this small compound
      to bionanotechnology. We discuss relevant chemical aspects in this context
      followed by an overview of its self-assembly capabilities both as a free molecule
      and when conjugated to a polymer. Further, cholesterol in the context of
      liposomes is reviewed and its impact ranging from biosensing to drug delivery is
      outlined. Cholesterol is and will be an indispensable player in
      bionanotechnology, contributing to the progress of this potent field of research.

PMID- 23172229
TI  - Cardiolipin-dependent reconstitution of respiratory supercomplexes from purified
      Saccharomyces cerevisiae complexes III and IV.
AB  - Here, we report for the first time in vitro reconstitution of the respiratory
      supercomplexes from individual complexes III and IV. Complexes III and IV were
      purified from Saccharomyces cerevisiae mitochondria. Complex III contained eight
      molecules of cardiolipin, and complex IV contained two molecules of cardiolipin,
      as determined by electrospray ionization-mass spectrometry. Complex IV also
      contained Rcf1p. No supercomplexes were formed upon mixing of the purified
      complexes, and low amounts of the supercomplex trimer III(2)IV(1) were formed
      after reconstitution into proteoliposomes containing only phosphatidylcholine and
      phosphatidylethanolamine. Further addition of cardiolipin to the proteoliposome
      reconstitution mixture resulted in distinct formation of both the III(2)IV(1)
      supercomplex trimer and III(2)IV(2) supercomplex tetramer. No other anionic
      phospholipid was as effective as cardiolipin in supporting tetramer formation.
      Phospholipase treatment of complex IV prevented trimer formation in the absence
      of cardiolipin. Both trimer and tetramer formations were restored by cardiolipin.
      Analysis of the reconstituted tetramer by single particle electron microscopy
      confirmed native organization of individual complexes within the supercomplex. In
      conclusion, although some trimer formation occurred dependent only on tightly
      bound cardiolipin, tetramer formation required additional cardiolipin. This is
      consistent with the high cardiolipin content in the native tetramer. The
      dependence on cardiolipin for supercomplex formation suggests that changes in
      cardiolipin levels resulting from changes in physiological conditions may control
      the equilibrium between individual respiratory complexes and supercomplexes in
      vivo.

PMID- 23172233
TI  - Computation of DNP coupling factors of a nitroxide radical in toluene: seamless
      combination of MD simulations and analytical calculations.
AB  - Dynamic nuclear polarization (DNP) employs paramagnetic species to increase the
      NMR signal of nuclear spins. In liquids, the efficiency of the effect depends on
      the strength of the interaction between the electron and nuclear spins and the
      time scales on which this interaction is modulated by the physical motion of the
      spin-bearing molecules. An approach to quantitatively predict the contribution of
      molecular motions to the DNP enhancement using molecular dynamics (MD)
      simulations is developed and illustrated for the nitroxide radical TEMPOL in
      liquid toluene. A multi-resolution strategy that combines explicit treatment of
      the solvent at short distances from the free radical with implicit description at
      large intermolecular distances is adopted. Novel analytical expressions are
      obtained to correct for the finite spatial extent of the MD simulations. The
      atomistic and analytical descriptions are sewn seamlessly together by ensuring
      that for molecular trajectories that start in the near (explicit) region and end
      in the distant (implicit) region the analytical dipolar spectral densities
      reproduce the MD estimates. The spectral densities obtained from the developed
      approach are used to calculate DNP coupling factors separately for the ring and
      methyl protons of toluene. The agreement with previously reported experimental
      DNP data at a magnetic field of 3.4 T is noteworthy and encouraging. Maximum
      obtainable DNP enhancements at other magnetic fields are predicted.

PMID- 23172232
TI  - Digitally programmable microfluidic automaton for multiscale combinatorial mixing
      and sample processing.
AB  - A digitally programmable microfluidic Automaton consisting of a 2-dimensional
      array of pneumatically actuated microvalves is programmed to perform new
      multiscale mixing and sample processing operations. Large (MUL-scale) volume
      processing operations are enabled by precise metering of multiple reagents within
      individual nL-scale valves followed by serial repetitive transfer to programmed
      locations in the array. A novel process exploiting new combining valve concepts
      is developed for continuous rapid and complete mixing of reagents in less than
      800 ms. Mixing, transfer, storage, and rinsing operations are implemented
      combinatorially to achieve complex assay automation protocols. The practical
      utility of this technology is demonstrated by performing automated serial
      dilution for quantitative analysis as well as the first demonstration of on-chip
      fluorescent derivatization of biomarker targets (carboxylic acids) for microchip
      capillary electrophoresis on the Mars Organic Analyzer. A language is developed
      to describe how unit operations are combined to form a microfluidic program.
      Finally, this technology is used to develop a novel microfluidic 6-sample
      processor for combinatorial mixing of large sets (>2(6) unique combinations) of
      reagents. The digitally programmable microfluidic Automaton is a versatile
      programmable sample processor for a wide range of process volumes, for multiple
      samples, and for different types of analyses.

PMID- 23172236
TI  - Bridging the segment-prosody divide in speech production and perception.

PMID- 23172237
TI  - At the edge of intonation: the interplay of utterance-final F0 movements and
      voiceless fricative sounds.
AB  - The paper is concerned with the 'edge of intonation' in a twofold sense. It
      focuses on utterance-final F0 movements and crosses the traditional segment
      prosody divide by investigating the interplay of F0 and voiceless fricatives in
      speech production. An experiment was performed for German with four types of
      voiceless fricatives: /f/, /s/, /?/ and /x/. They were elicited with scripted
      dialogues in the contexts of terminal falling statement and high rising question
      intonations. Acoustic analyses show that fricatives concluding the high rising
      question intonations had higher mean centres of gravity (CoGs), larger CoG ranges
      and higher noise energy levels than fricatives concluding the terminal falling
      statement intonations. The different spectral-energy patterns are suitable to
      induce percepts of a high 'aperiodic pitch' at the end of the questions and of a
      low 'aperiodic pitch' at the end of the statements. The results are discussed
      with regard to the possible existence of 'segmental intonation' and its
      implication for F0 truncation and the segment-prosody dichotomy, in which
      segments are the alleged troublemakers for the production and perception of
      intonation.

PMID- 23172234
TI  - Strategies to query and display allergy-derived epitope data from the immune
      epitope database.
AB  - The recognition of specific epitopes on allergens by antibodies and T cells is a
      key element in allergic processes. Analysis of epitope data may be of interest
      for basic immunopathology or for potential application in diagnostics or
      immunotherapy. The Immune Epitope Database (IEDB) is a freely available
      repository of epitope data from infectious disease agents, as well as epitopes
      defined for allergy, autoimmunity, and transplantation. The IEDB curates the
      experiments associated with each epitope and thus provides a variety of different
      ways to search the data. This review aims to demonstrate the utility of the IEDB
      and its query strategies, including searching by epitope structure
      (peptidic/nonpeptidic), by assay methodology, by host, by the allergen itself, or
      by the organism from which the allergen was derived. Links to tools for
      visualization of 3-D structures, epitope prediction, and analyses of B and T cell
      reactivity by host response frequency score are also highlighted.

PMID- 23172238
TI  - Intonation adapts to lexical tone: the case of Kammu.
AB  - In this paper, we investigate how lexical tones interact with intonation, using
      data from the Austroasiatic language Kammu, one of few languages with two
      dialects whose only major phonological difference is the presence or absence of
      lexical tones. Northern (and Western) Kammu have developed tones in connection
      with the merger of voiceless and voiced initial consonants, while the non-tonal
      Eastern dialect kept the segmental opposition with no tones. We found the
      following prosodic hierarchy: (1) lexical tones, (2) phrase-final boundary tone,
      (3) focus marking. The results strongly suggest that the intonational systems of
      the two Kammu dialects are basically identical, and that the main differences
      between the dialects are adaptations of intonation patterns to the lexical tones
      when the identities of the tones are jeopardized.

PMID- 23172239
TI  - Making sense of outliers.
AB  - Phonetic inquiry, particularly of the kind which looks at large numbers of items,
      frequently asks what a 'typical' example of a phenomenon of speech is like. For
      example, in describing the plosives of a language, it is common to calculate
      average closure durations or voice onset times in some contexts. In this paper,
      the focus is on examples from natural conversation where there are untypical
      patterns, and where the item of interest is, in statistical terms, an outlier.
      Outliers are generally excluded from linguistic analysis, and may be treated as
      e.g. production errors. The paper shows instead that at least some outliers are
      in fact part of a meaningful practice, and an orderly method by which speakers
      can create meaning. The phenomenon more precisely is that of intensifying
      emphasis, which has been described for German. We consider its phonetic exponents
      in American English, which are both 'prosodic' and 'segmental'. We provide an
      account of function based on participants' own use and displayed understanding of
      the phenomenon, and argue for a structurally rich account of the phenomenon which
      includes aspects of turn construction and sequential organisation.

PMID- 23172240
TI  - The perception of lexical stress in German: effects of segmental duration and
      vowel quality in different prosodic patterns.
AB  - Several decades of research, focusing on English, Dutch and German, have set up a
      hierarchy of acoustic properties for cueing lexical stress. It attributes the
      strongest cue to criterial-level f0 change, followed by duration, but low weight
      to energy and to stressed-vowel spectra. This paper re-examines the established
      view with new data from German. In the natural productions of the German word
      pair Kaffee 'coffee' - Cafe 'locality' (with initial vs. final stress in a North
      German pronunciation), vowel duration was manipulated in a complementary fashion
      across the two syllables in five steps, spanning the continuum from initial to
      final stress on each word. The two base words provided different vowel qualities
      as the second variable, the intervocalic fricative was varied in two values, long
      and short, taken from Cafe and Kaffee, and the generated test words were inserted
      in a low f0 tail and in a high f0 hat-pattern plateau, which both eliminated f0
      change as a cue to lexical stress. The sentence stimuli were judged in two
      listening experiments by 16 listeners in each as to whether the first or the
      second syllable of the test word was stressed. The results show highly
      significant effects of vowel duration, vowel quality and fricative duration. The
      combined vowel-quality and fricative variable can outweigh vowel duration as a
      cue to lexical stress. The effect of the prosodic frame is only marginal,
      especially related to a rhythmic factor. The paper concludes that there is no
      general hierarchy with a fixed ranking of the variables traditionally adduced to
      signal lexical stress. Every prosodic embedding of segmental sequences defines
      the hierarchy afresh.

PMID- 23172241
TI  - Intelligibility of non-natively produced Dutch words: interaction between
      segmental and suprasegmental errors.
AB  - In the field of second language research many adhere to the idea that prosodic
      errors are more detrimental to the intelligibility of non-native speakers than
      segmental errors. The current study reports on a series of experiments testing
      the influence of stress errors and segmental errors, and a combination of these,
      on native processing of words produced by intermediate speakers of Dutch as a
      second language with either Mandarin Chinese or French as mother tongue. The
      results suggest that both stress and segmental errors influence processing, but
      suprasegmental errors do not outweigh segmental errors. It seems that a more
      'foreign' generic pronunciation leads to a greater impact of (supra)segmental
      errors, suggesting that segmental and prosodic deviations should not be viewed as
      independent factors in processing non-native speech.

PMID- 23172242
TI  - The CF-ABLE score: a novel clinical prediction rule for prognosis in patients
      with cystic fibrosis.
AB  - BACKGROUND: Determining prognosis and predicting outcomes in cystic fibrosis (CF)
      is a complex issue, and there have been very few clinically applicable models for
      this. The aim was to create a simple, practical outcome prediction tool for CF.
      METHODS: Forty-nine consecutive patients with CF from a single center were
      studied over an 84-month period (2004-2010). All baseline clinical parameters
      were gathered, and FEV1 measurements were analyzed over the study period. Using
      patterns of FEV1 decline, a tipping point of 52.8% predicted was identified.
      Other clinical variables were analyzed and correlated with outcome. Poor outcome
      was defined as death or transplantation. Using age, BMI, lung function (ie,
      FEV1), and number of exacerbations in the past 3 months, the CF-ABLE score was
      created. The score was validated for data from 370 patients from the national
      Cystic Fibrosis Registry of Ireland. RESULTS: The ABLE score uses clinical
      parameters that are measured at every clinic visit and scored on a scale from 0
      to 7. If FEV1 is < 52%, then 3.5 points are added; if the number of exacerbations
      in the past 3 months is > 1, then 1.5 points are added; if BMI is < 20.1 kg/m2 or
      age < 24 years, each receive 1 point. CONCLUSIONS: Patients with a low score have
      a very low risk of death or lung transplantation within 4 years; however, as the
      score increases, the risk significantly increases. Patients who score > 5 points
      have a 26% risk of poor outcome within 4 years. This score is simple and
      applicable and better predicts outcome than FEV1 alone.

PMID- 23172243
TI  - Integrating cell-free biosyntheses of heme prosthetic group and apoenzyme for the
      synthesis of functional P450 monooxygenase.
AB  - Harnessing the isolated protein synthesis machinery, cell-free protein synthesis
      reproduces the cellular process of decoding genetic information in artificially
      controlled environments. More often than not, however, generation of functional
      proteins requires more than simple translation of genetic sequences. For
      instance, many of the industrially important enzymes require non-protein
      prosthetic groups for biological activity. Herein, we report the complete cell
      free biogenesis of a heme prosthetic group and its integration with concurrent
      apoenzyme synthesis for the production of functional P450 monooxygenase. Step
      reactions required for the syntheses of apoenzyme and the prosthetic group have
      been designed so that these two separate pathways take place in the same reaction
      mixture, being insulated from each other. Combined pathways for the synthesis of
      functional P450 monooxygenase were then further integrated with in situ assay
      reactions to enable real-time measurement of enzymatic activity during its
      synthesis.

PMID- 23172244
TI  - Facile synthesis of novel Ni(II)-based metal-organic coordination polymer
      nanoparticle/reduced graphene oxide nanocomposites and their application for
      highly sensitive and selective nonenzymatic glucose sensing.
AB  - The present paper reports on the facile preparation of novel Ni(II)-based metal
      organic coordination polymer nanoparticle/reduced graphene oxide (NiCPNP/rGO)
      nanocomposites for the first time. The formation of the nanocomposites occurs in
      a single step, carried out by hydrothermal treatment of the mixture of tannic
      acid functioned graphene oxide and NiCl(2) aqueous solution in N,N
      dimethylformamide. It is found that the NiCPNP/rGO nanocomposite-modified
      electrode shows high electrocatalytic activity for glucose oxidation in alkaline
      medium. This nonenzymatic glucose sensor exhibits high selectivity toward glucose
      and the linear range and limit of detection are estimated to be from 0.01 to 8.75
      mM (r: 0.997) and 0.14 MUM with a signal-to-noise ratio of 3, respectively. The
      application of this glucose sensor in human blood serum has also been
      demonstrated successfully.

PMID- 23172245
TI  - Aortic aneurysm disease vs. aortic occlusive disease: differences in outcome and
      intensive care resource utilisation after elective surgery: an observational
      study.
AB  - CONTEXT: Abdominal aortic surgery is a high-risk procedure, with aortic aneurysm
      and aortic occlusive diseases being the main indications. These groups are often
      regarded as having equal perioperative risk profiles. Previous reports suggest
      that the haemodynamic and inflammatory response to aortic clamping is more
      pronounced in patients with aortic aneurysm disease, which may affect outcome.
      OBJECTIVES: The aim of this observational cohort study was to evaluate outcome
      after open elective abdominal aortic surgery, hypothesising a higher 30-day
      mortality, a higher incidence of postoperative organ dysfunction and a longer
      length of stay in patients with aortic aneurysm compared with aortic occlusive
      disease. DESIGN: Cohort observational study based on prospective registrations
      from national databases. SETTING: Eight Danish hospitals, including four
      university and four non-university centres, from 1 January 2007 to 1 March 2010.
      PATIENTS: One thousand two hundred and ninety-three patients scheduled for
      primary open elective, aortoiliac bypass or aortofemoral bypass procedures or
      abdominal aortic aneurysm repair. MAIN OUTCOME MEASURES: Mechanical ventilation,
      acute dialysis, use of vasopressors or inotropes, ICU stay more than 24 h,
      hospital length of stay and mortality. RESULTS: Compared with aortic occlusive
      disease, more patients with aortic aneurysm disease had ICU stays more than 24 h
      (62 vs. 45%, P < 0.001) and more often needed acute dialysis or ventilatory
      support (17 vs. 11%, P = 0.04). No difference was found in hospital length of
      stay, 30-day mortality or overall risk of death. Mortality after 1 year was
      higher in patients with aortic aneurysm disease (8 vs. 4.7%, P = 0.04).
      CONCLUSION: Patients with abdominal aortic aneurysms were at higher risk of
      developing postoperative organ dysfunction and required more ICU resources than
      patients with occlusive disease, despite no differences in hospital length of
      stay or 30-day mortality. Distinguishing between these two diseases may be useful
      in planning and distribution of ICU resources and for in future studies.

PMID- 23172246
TI  - Recovery of train-of-four ratio to 0.70 and 0.90 is delayed in type 2 diabetes
      with vecuronium-induced neuromuscular block.
AB  - CONTEXT: The recovery profile of train-of-four ratio to more than 0.70 in
      patients with diabetes mellitus has not been well investigated. OBJECTIVE: Our
      primary objective was to evaluate the spontaneous recovery profile of
      neuromuscular block by vecuronium until train-of-four ratio more than 0.90 in
      patients with type 2 diabetes mellitus compared with controls, using first dorsal
      interosseous electromyography. DESIGN: Single-centre prospective case-control
      study. SETTING: The operating theatres of Fukuoka University Hospital. PATIENTS:
      Fourteen adults with type 2 diabetes mellitus (diabetes mellitus group) and 14
      control patients (control group) were included in this study. INTERVENTION:
      Evoked responses to train-of-four stimuli were measured by electromyography at
      the first dorsal interosseous muscle. General anaesthesia was induced with
      propofol, fentanyl and remifentanil. Vecuronium (0.1  mg kg) was administered to
      all patients. Anaesthesia was maintained with propofol, fentanyl and
      remifentanil. The neuromuscular block was assessed until spontaneous recovery to
      train-of-four ratio more than 0.90. MAIN OUTCOME MEASURES: Recovery times to
      train-of-four ratio 0.70 and 0.90. RESULTS: Recovery times to train-of-four ratio
      0.70 and 0.90 were significantly longer in the diabetes mellitus group than the
      control group (P = 0.041 and P = 0.027, respectively). The time from train-of
      four ratio 0.25 to 0.90 was also significantly longer in the diabetes mellitus
      group than the control group (P = 0.029). In five of 14 patients in the diabetes
      mellitus group, the time from train-of-four ratio 0.25 to 0.90 was longer than 60
      min, which is longer than the duration of action of neostigmine. The time from
      train-of-four ratio 0.25 to 0.90 was longer than 60  min in only one of 14 in the
      control group. CONCLUSION: Recovery times to train-of-four ratio 0.70 and 0.90
      were delayed in patients with type 2 diabetes mellitus. Neuromuscular block by
      vecuronium should be carefully monitored in patients with type 2 diabetes
      mellitus until recovery of train-of-four ratio to a safe level is confirmed.

PMID- 23172248
TI  - Emotional Impulsivity and Emotional and Behavioral Difficulties Among Children
      With ADHD: An Ecological Momentary Assessment Study.
AB  - OBJECTIVE: Children with ADHD often demonstrate impulsive shifts in emotion,
      characterized by sudden and intense shifts in affect. This study examined the
      effects of emotional impulsivity over time on the emotional and behavioral
      functioning of children with ADHD using ecological momentary assessment (EMA).
      METHOD: Twenty-seven 8- to 12-year-old children with ADHD, and their parents,
      completed baseline measures of the children's emotional and behavioral
      functioning. Parents and children then completed an EMA protocol, whereby they
      each rated the child's affect three times daily for 28 days. RESULTS:
      Hierarchical regression analyses strongly supported the relation of greater EMA
      derived emotional impulsivity to children's increased emotional and behavioral
      difficulties. These effects were evident across reporters and were maintained
      after controlling for baseline emotion dysregulation. CONCLUSION: Overall, this
      study demonstrated the utility of EMA-based assessments and suggested that
      emotional impulsivity may play an important role in the emotional and behavioral
      functioning of children with ADHD.

PMID- 23172251
TI  - A quality assessment of cardiac auscultation material on YouTube.
AB  - BACKGROUND: YouTube is a highly utilized Web site that contains a large amount of
      medical educational material. Although some studies have assessed the education
      material contained on the Web site, little analysis of cardiology content has
      been made. This study aimed to assess the quality of videos relating to heart
      sounds and murmurs contained on YouTube. HYPOTHESIS: We hypothesized that the
      quality of video files purporting to provide education on heart auscultation
      would be highly variable. METHODS: Videos were searched for using the terms
      "heart sounds," "heart murmur," and "heart auscultation." A built-in educational
      filter was employed, and manual rejection of non-English language and nonrelated
      videos was undertaken. Remaining videos were analyzed for content, and suitable
      videos were scored using a purpose-built tool. RESULTS: YouTube search located
      3350 videos in total, and of these, 22 were considered suitable for scoring. The
      average score was 4.07 out of 7 (standard deviation, 1.35). Six videos scored 5.5
      or greater and 5 videos scoring 2.5 or less. There was no correlation between
      video score and YouTube indices of preference (hits, likes, dislikes, or search
      page). The quality of videos found in this study was highly variable. YouTube
      indications of preference were of no value in determining the value of video
      content. Therefore, teaching institutions or professional societies should
      endeavor to identify and highlight good online teaching resources. CONCLUSIONS:
      YouTube contains many videos relating to cardiac auscultation, but very few are
      valuable education resources.

PMID- 23172249
TI  - Alterations in the motor neuron-renshaw cell circuit in the Sod1(G93A) mouse
      model.
AB  - Motor neurons become hyperexcitable during progression of amyotrophic lateral
      sclerosis (ALS). This abnormal firing behavior has been explained by changes in
      their membrane properties, but more recently it has been suggested that changes
      in premotor circuits may also contribute to this abnormal activity. The specific
      circuits that may be altered during development of ALS have not been
      investigated. Here we examined the Renshaw cell recurrent circuit that exerts
      inhibitory feedback control on motor neuron firing. Using two markers for Renshaw
      cells (calbindin and cholinergic nicotinic receptor subunit alpha2 [Chrna2]), two
      general markers for motor neurons (NeuN and vesicular acethylcholine transporter
      [VAChT]), and two markers for fast motor neurons (Chondrolectin and calcitonin
      related polypeptide alpha [Calca]), we analyzed the survival and connectivity of
      these cells during disease progression in the Sod1(G93A) mouse model. Most
      calbindin-immunoreactive (IR) Renshaw cells survive to end stage but downregulate
      postsynaptic Chrna2 in presymptomatic animals. In motor neurons, some markers are
      downregulated early (NeuN, VAChT, Chondrolectin) and others at end stage (Calca).
      Early downregulation of presynaptic VAChT and Chrna2 was correlated with
      disconnection from Renshaw cells as well as major structural abnormalities of
      motor axon synapses inside the spinal cord. Renshaw cell synapses on motor
      neurons underwent more complex changes, including transitional sprouting
      preferentially over remaining NeuN-IR motor neurons. We conclude that the loss of
      presynaptic motor axon input on Renshaw cells occurs at early stages of ALS and
      disconnects the recurrent inhibitory circuit, presumably resulting in diminished
      control of motor neuron firing. J. Comp. Neurol. 521:1449-1469, 2013. (c) 2012
      Wiley Periodicals, Inc.

PMID- 23172252
TI  - Synthesis and assembly of Pd nanoparticles on graphene for enhanced
      electrooxidation of formic acid.
AB  - Monodisperse 4.5 nm Pd nanoparticles (NPs) were synthesized by solution phase
      reduction of palladium acetylacetonate with morpholine borane in a mixture of
      oleylamine and 1-octadecene. These NPs were assembled on graphene uniformly in
      the form of a monolayer, and showed much enhanced catalysis for electrooxidation
      of formic acid. The work demonstrates the great potential of graphene as a
      support to enhance NP catalysis and stability for important chemical oxidation
      reactions.

PMID- 23172253
TI  - Suppression of Sr surface segregation in La(1-x)Sr(x)Co(1-y)Fe(y)O(3-delta): a
      first principles study.
AB  - Based on systematic first principles calculations, we investigate Sr surface
      segregation (SSS) in La(1-x)Sr(x)Co(1-y)Fe(y)O(3-delta) (LSCF) (a typical
      perovskite ABO(3) compound), a bottleneck causing efficiency degradation of solid
      oxide fuel cells. We identify two basic thermodynamic driving forces for SSS and
      suggest two possible ways to suppress SSS: applying compressive strain and
      reducing surface charge. We show that compressive strain can be applied through
      doping of larger elements and surface coating; surface charge can be reduced
      through doping of higher-valence elements in the Sr- and B-site or lower-valence
      elements in the La-site and introducing surface A-site vacancies. The net effect
      of oxygen vacancy is to enhance SSS because its effect of increasing surface
      charge overrides its effect of inducing compressive strain, while Co substitution
      of Fe always enhances SSS because it induces tensile strain as well as increases
      surface charge. Our results explain the recent experimental observation of SSS
      suppression in LSCF by a La(1-x)Sr(x)MnO(3-delta) (LSM) coating.

PMID- 23172254
TI  - Perampanel approved for epilepsy.

PMID- 23172255
TI  - Meningitis outbreak challenges hospital pharmacies.

PMID- 23172257
TI  - Global pharmacy group celebrates 100 years.

PMID- 23172258
TI  - International hospital pharmacy section's work on Basel statements continues.

PMID- 23172259
TI  - Multidisciplinary clinic for patients with newly diagnosed chronic kidney
      disease.

PMID- 23172260
TI  - Developing pharmacy technicians across the leadership spectrum.

PMID- 23172261
TI  - Social media profiles: striking the right balance.

PMID- 23172262
TI  - Toward atonement for pharmacy compounding tragedies.

PMID- 23172263
TI  - Role of procalcitonin in guiding antibiotic therapy.
AB  - PURPOSE: The role of procalcitonin in guiding antibiotic therapy is reviewed.
      SUMMARY: Procalcitonin is a prohormone for calcitonin, which is secreted by the
      parafollicular cells of the thyroid gland. The biological activity of
      procalcitonin is significantly different from calcitonin and is believed to be
      part of the complex inflammatory cascade of the immune system. Procalcitonin has
      been shown to be elevated in bacterial infections but not in viral infections or
      other inflammatory conditions. The first published study that suggested that
      procalcitonin levels increased in the presence of bacterial infection was
      conducted in France in the early 1990s. Numerous studies have been conducted
      using procalcitonin-guided therapy to reduce antibiotic use. These studies were
      performed in one of three clinical settings: outpatient primary care (two
      multicenter, noninferiority studies of patients with upper- and lower-respiratory
      tract infections), emergency room and inpatient (five studies in patients with
      chronic obstructive pulmonary disease, exacerbation, bronchitis, or community
      acquired pneumonia), and the intensive care unit (ICU) (two studies in medical
      ICU patients and two in postoperative ICU patients with infection or sepsis).
      Based on the findings of these studies, a cutoff value of 0.25 MUg/L in non-ICU
      patients or of 0.5 MUg/L in ICU patients seems appropriate for making a decision
      about the initiation and discontinuation of antibiotic therapy. In patients with
      a significantly elevated baseline procalcitonin level, a subsequent drop of >80%
      appears to be reasonable for discontinuing antibiotics. CONCLUSION: Published
      evidence supports the use of procalcitonin as a biomarker of bacterial infection
      that can be used to reduce antibiotic exposure.

PMID- 23172264
TI  - Apparent interaction between telaprevir and warfarin in a patient with chronic
      hepatitis C viral infection.
AB  - PURPOSE: A probable interaction between warfarin and a recently approved protease
      inhibitor used in a triple-drug regimen for hepatitis C virus (HCV) infection is
      reported. SUMMARY: A 45-year-old Hispanic man seen at an anticoagulation clinic
      was found to have an International Normalized Ratio (INR) of 6.0; for the
      preceding eight months, INR values in the therapeutic range (2.5-3.5) had been
      maintained on a stable regimen of warfarin sodium 6 mg daily. Two days before the
      clinic visit, triple therapy with peginterferon alfa-2a, ribavirin, and
      telaprevir had been initiated for chronic HCV infection. The patient was
      instructed to skip two warfarin sodium doses and then resume its use at a reduced
      daily dose (5 mg), but he reported missing five doses, resulting in a below
      target INR. An increase in the weekly warfarin dose of 50% above the baseline
      dose was required to reattain a target INR. The warfarin dosing requirement began
      to decline only after the man finished the prescribed 12-week course of
      telaprevir. CONCLUSION: The INR of an HCV-infected man who was on a stable
      warfarin regimen was found to be above the target range two days after triple
      therapy including telaprevir was begun. The INR fell below the target range after
      warfarin therapy was ceased for five days and returned to that range after
      warfarin was restarted and its dosage gradually increased to 1.5 times the
      baseline dosage. The warfarin dosage needed to maintain a target INR fell to
      nearly its baseline level after telaprevir was discontinued.

PMID- 23172265
TI  - Evaluation of a pediatric continuous-infusion vancomycin therapy guideline.
AB  - PURPOSE: An institutional guideline for converting pediatric patients to
      continuous-infusion vancomycin (CIV) therapy if therapeutic targets are not
      achieved with intermittent i.v. dosing was evaluated. METHODS: All patients
      within a specified age range (>6 months but <19 years) who were converted to CIV
      therapy for pneumonia or osteomyelitis during the 2 years after guideline
      implementation were included in the evaluation. The guideline calls for
      conversion to CIV therapy if goals for trough serum vancomycin concentration
      (SVC) are not attained with escalating intermittent-infusion vancomycin (IIV)
      dosing. Primary outcome measures included the rate of attainment of the goal
      steady-state trough SVC (15-20 mg/L), preferably within 24-48 hours, the adequacy
      of an empirical dosing strategy, and adverse events. Secondary study outcomes
      included final vancomycin doses and the time to attainment of therapeutic SVCs.
      RESULTS: Within 24-48 hours after conversion to CIV therapy, the mean initial
      plateau SVC in the evaluated cases (n = 15) was 20.2 mg/L; the mean of all SVCs
      was 19.1 mg/L. The range of dosages required to achieve a plateau SVC of 15 mg/L
      was 23.8-65.4 mg/kg/day (median, 41 mg/kg/day). The mean +/- S.D. vancomycin
      dosage at the end of CIV therapy was 44.3 +/- 12.8 mg/kg/day. Monitoring of serum
      creatinine, urine output, and glomerular filtration rate indicated that no
      patients developed nephrotoxicity during CIV therapy. CONCLUSION: Conversion from
      IIV to CIV therapy in selected pediatric patients appeared to be safe and well
      tolerated, with few adverse effects noted. Using the institutional CIV dosing
      guideline, goal plateau SVC values were attained in most patients within 24-48
      hours.

PMID- 23172266
TI  - Effect of genetic polymorphisms on effectiveness of low-dose azathioprine in
      Japanese patients with systemic lupus erythematosus.
AB  - PURPOSE: The effect of genetic polymorphisms on the effectiveness of low-dose
      azathioprine in Japanese patients with systemic lupus erythematosus (SLE) was
      studied. METHODS: Sixty-one unrelated Japanese patients with SLE treated with
      azathioprine were included in the study. The selected genetic polymorphisms
      evaluated in the analysis were ITPA 138G>A, ITPA 563G>A, IMPDH 1575A>G, XO
      837C>T, XO 2211C>T, XO 3030C>T, and MRP4 2269G>A. The DNA isolation and
      genotyping procedures for ITPA 94C>A and TPMT*3C were the same as those in a
      previous study. Genotyping of ITPA 138G>A, ITPA 563G>A, IMPDH 1575A>G, MRP4
      2269G>A, XO 837C>T, XO 2211C>T, and XO 3030C>T was performed using a validated
      genotyping assay. The SLE disease activity index (SLEDAI) score was used as a
      marker for the efficacy of azathioprine treatment, and the correlations between
      the changes in the SLEDAI score and the considered polymorphisms were evaluated.
      RESULTS: The mean SLE duration, SLEDAI score, and azathioprine dosage prescribed
      were 5.6 years, 6.0, and 1 mg/kg/day, respectively. Small (but not significant) p
      values suggested a tendency for the reduction in the SLEDAI score to be greater
      in patients with the ITPA 94A allele. Further, the ITPA 94C>A polymorphism
      correlated highly with the change in the SLEDAI score. However, there were no
      significant associations among TPMT*3C, ITPA 138G>A, ITPA 563G>A, IMPDH 1575A>G,
      XO 837C>T, XO 2211C>T, and XO 3030C>T and the mean changes in the SLEDAI score
      over the one-year investigation period. CONCLUSION: The ITPA 94C>A polymorphism
      was found to possibly influence the clinical response to low-dose azathioprine in
      Japanese patients with SLE. The other studied single-nucleotide polymorphisms
      appeared to have little influence on the effectiveness of azathioprine.

PMID- 23172267
TI  - Pharmacy forecast 2013-2017: strategic planning advice for pharmacy departments
      in hospitals and health systems: executive summary of a trends report from the
      center for health-system pharmacy leadership, ASHP research and education
      foundation.

PMID- 23172268
TI  - Changes to medication-use processes after overdose of U-500 regular insulin.
AB  - PURPOSE: Modifications made to medication-use processes after an overdose of U
      500 regular insulin are described. SUMMARY: After a medication error occurred
      with U-500 regular insulin, a multidisciplinary team of physicians, nurses,
      advanced-practice nurses, and pharmacists was created to review and improve the
      ordering, dispensing, and administration processes associated with U-500 regular
      insulin. The group determined that current safety practices for managing insulin
      were inadequate. New safety processes specific to U-500 regular insulin were
      developed and implemented. Vials of U-500 regular insulin are no longer dispensed
      to nursing units and are stored only in the pharmacy and separated from other
      insulins. The ordering of U-500 regular insulin is limited to the endocrinology
      service, and all orders are written using a specialized U-500 regular insulin
      order set. The option for i.v. administration for U-500 regular insulin was
      removed from the pharmacy order-entry system; thus, only the subcutaneous route
      is entered by the pharmacist. In addition, patient-specific doses of U-500
      regular insulin are prepared in the pharmacy using only tuberculin syringes that
      require a double check by two pharmacists. These syringes are delivered to
      patient care areas in a bag distinguishing the medication as "high alert." One
      last safety check involving a two-nurse check at the bedside to confirm correct
      medication administration is performed. Lastly, patient education material
      specifically for U-500 regular insulin is available online. CONCLUSION: A
      multidisciplinary team recommended modifications to the medication-use system
      regarding U-500 regular insulin after review of a medication error. No errors
      involving U-500 regular insulin have been reported since implementation of the
      changes.

PMID- 23172269
TI  - ASHP statement on use of social media by pharmacy professionals: developed
      through the ASHP pharmacy student forum and the ASHP section of pharmacy
      informatics and technology and approved by the ASHP Board of Directors on April
      13, 2012, and by the ASHP House of Delegates on June 10, 2012.

PMID- 23172270
TI  - Biocatalytic reduction of short-chain carboxylic acids into their corresponding
      alcohols with syngas fermentation.
AB  - Short-chain carboxylic acids generated by various mixed- or pure-culture
      fermentation processes have been considered valuable precursors for production of
      bioalcohols. While conversion of carboxylic acids into alcohols is routinely
      performed with catalytic hydrogenation or with strong chemical reducing agents,
      here, a biological conversion route was explored. The potential of
      carboxydotrophic bacteria, such as Clostridium ljungdahlii and Clostridium
      ragsdalei, as biocatalysts for conversion of short-chain carboxylic acids into
      alcohols, using syngas as a source of electrons and energy is demonstrated.
      Acetic acid, propionic acid, n-butyric acid, isobutyric acid, n-valeric acid, and
      n-caproic acid were converted into their corresponding alcohols. Furthermore,
      biomass yields and fermentation stoichiometry from the experimental data were
      modeled to determine how much metabolic energy C. ljungdahlii generated during
      syngas fermentation. An ATP yield of 0.4-0.5 mol of ATP per mol CO consumed was
      calculated in the presence of hydrogen. The ratio of protons pumped across the
      cell membrane versus electrons transferred from ferredoxin to NAD(+) via the Rnf
      complex is suggested to be 1.0. Based on these results, we provide suggestions
      how n-butyric acid to n-butanol conversion via syngas fermentation can be further
      improved.

PMID- 23172271
TI  - A CN- specific turn-on phosphorescent probe with probable application for
      enzymatic assay and as an imaging reagent.
AB  - A new "turn-on" luminescence probe for imaging the uptake of 0.2 ppm inorganic
      CN(-) in live HeLa cells as well as for probing the CN(-) generation through an
      enzymatic process in a virtual aqueous medium at appropriate pH.

PMID- 23172274
TI  - Spatially resolved electrochemical sensing of chemical gradients.
AB  - Chemical gradients drive a diverse set of biological processes ranging from nerve
      transduction to ovulation. At present, the most common method for quantifying
      chemical gradients is microscopy. Here, a new concept for probing spatial and
      temporal chemical gradients is reported that uses a multi-layer microfluidic
      device to measure analyte concentration as a function of lateral position in a
      microfluidic channel using electrochemistry in a format that is readily adaptable
      to multi-analyte sensing.

PMID- 23172275
TI  - [Gut microbial influence and probiotics on colorectal cancer].
AB  - The human intestinal microbiota is a community of 10(13)-10(14) microorganisms
      that harbor in the intestine and normally participate in a symbiotic relationship
      with human. Technical and conceptual advances have enabled rapid progress in
      characterizing the taxonomic composition, metabolic capacity and immunomodulatory
      activity of the human intestinal microbiota. Their collective genome, defined as
      microbiome, is estimated to contain >=150 times as many genes as 2.85 billion
      base pair human genome. The intestinal microbiota and its microbiome form a
      diverse and complex ecological community that profoundly impact intestinal
      homeostasis and disease states. It is becoming increasingly evident that the
      large and complex bacterial population of the large intestine plays an important
      role in colorectal carcinogenesis. Numerous studies show that gut immunity and
      inflammation have impact on the development of colorectal cancer. Additionally,
      bacteria have been linked to colorectal cancer by the production of toxic and
      genotoxic bacterial metabolite. In this review, we discuss the multifactorial
      role of intestinal microbiota in colorectal cancer and role for probiotics in the
      prevention of colorectal cancer.

PMID- 23172272
TI  - A placebo-controlled, randomized trial of mesenchymal stem cells in COPD.
AB  - BACKGROUND: COPD is a devastating disease affecting millions worldwide. As
      disease pathogenesis includes both chronic pulmonary and systemic inflammation,
      antiinflammatory effects of systemically administered mesenchymal stem cells
      (MSCs) may decrease inflammation, resulting in improved lung function and quality
      of life. The goal of this study was to assess safety and to perform an initial
      evaluation of the potential efficacy of systemic MSC administration to patients
      with moderate to severe COPD. METHODS: Sixty-two patients at six sites were
      randomized to double-blinded IV infusions of either allogeneic MSCs (Prochymal;
      Osiris Therapeutics Inc) or vehicle control. Patients received four monthly
      infusions (100 * 106 cells/infusion) and were subsequently followed for 2 years
      after the first infusion. End points included comprehensive safety evaluation,
      pulmonary function testing (PFT), and quality-of-life indicators including
      questionnaires, 6MWT, and assessments of systemic inflammation. RESULTS: All
      study patients completed the full infusion protocol, and 74% completed the 2-year
      follow-up. There were no infusional toxicities and no deaths or serious adverse
      events deemed related to MSC administration. There were no significant
      differences in the overall number of adverse events, frequency of COPD
      exacerbations, or worsening of disease in patients treated with MSCs. There were
      no significant differences in PFTs or quality-of-life indicators; however, an
      early, significant decrease in levels of circulating C-reactive protein (CRP) was
      observed in patients treated with MSCs who had elevated CRP levels at study
      entry. CONCLUSIONS: Systemic MSC administration appears to be safe in patients
      with moderate to severe COPD and provides a basis for subsequent cell therapy
      investigations. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT00683722; URL:
      www.clinicaltrials.gov.

PMID- 23172276
TI  - [Clinicopathologic characteristics of superficial gastric cancer diagnosed at
      primary health care institutions in 2011].
AB  - BACKGROUND/AIMS: Stomach cancer is prevalent in Korea. The purpose of this study
      was to evaluate the characteristics of superficial gastric cancers detected at
      SOK Sokpeynhan Internal Medical Network, the nationwide primary health care
      institutions. METHODS: We prospectively analysed the clinicopathologic and
      endoscopic characteristics of 218 superficial gastric cancer patients diagnosed
      using gastric endoscopy at SOK network from January 2011 through December 2011.
      RESULTS: The mean age was 58.5 years old and male to female ratio was 1.7 : 1.
      Asymptomatic patients were most common (45.0%). The macroscopic classification
      revealed that simple types (63.8%) were more common than complex types (36.2%).
      The most common type was IIc (28.4%) and other types were as follows; IIb
      (16.1%), IIb+IIc (13.3%), IIa (10.6%), III (9.2%), IIa+IIc (7.3%), IIc+IIa
      (6.0%), IIc+IIb (5.0%). The most commonly involved sites were the body (53.1%)
      and greater curvature (32.6%) of the stomach. The size of lesion was less than 1
      cm (69.3%) and less than 5 mm (33.5%) in diameter. The most common pathologic
      type was tubular adenocarcinoma (75.7%). Helicobacter pylori infection rate was
      50.2%. Fifty five percent of the cases were diagnosed via endoscopy of National
      Health Insurance Corporation screenings. CONCLUSIONS: Superficial gastric cancers
      in 2011 at primary health care SOK network were different from those of previous
      reports. Type IIc was most common but type IIb was more prevalent and the body
      and greater curvature of the stomach were the most commonly involved sites.
      Therefore, careful observation of the proximal gastric mucosa and mucosal color
      change is needed.

PMID- 23172277
TI  - [A survey of actual clinical application patterns in Korean diagnostic guidelines
      for inflammatory bowel disease].
AB  - BACKGROUND/AIMS: The aim of this study was to analyze the actual application
      patterns of how Korean diagnostic guidelines for inflammatory bowel disease (IBD)
      were applied in clinical practice. METHODS: Questionnaires regarding guidelines
      for ulcerative colitis (UC), Crohn's disease (CD), intestinal Behcet's disease
      (BD) and intestinal tuberculosis (TB), were distributed during the 2011 Korean
      Association for the Study of Intestinal Disease annual conference, and e-mail
      survey was additionally conducted. Forty eight questionnaires were collected.
      RESULTS: Most of responders (79.2%) were working at secondary (>=500 beds) or
      tertiary referral centers. For the necessity of guidelines, 93.8% of responders
      gave positive answers in UC; 95.8% in CD; 81.3% in BD; 91.7% in TB. Of the
      clinicians, 95.8%, 91.7%, 64.6%, 77.1% had read UC, CD, BD and TB guideline, and
      87.0%, 93.2%, 90.3%, and 92.0% replied that diagnostic guidelines for UC, CD, BD
      and TB were helpful in practice, respectively. Practice patterns were changed in
      39.1%, 33.2%, 41.9%, and 54.1% of responders by UC, CD, BD and TB guidelines,
      respectively. For the needs of update, 58.7% of responders answered 'yes' in UC,
      54.5% in CD, 51.6% in BD and 48.7% in TB. There were differences between
      recommendations and practice patterns, including colonoscopy surveillance in UC,
      radiological examinations for small bowel in CD and for intestinal obstruction in
      UC, or biopsy method in UC, CD and TB, and diagnostic criteria in BD.
      CONCLUSIONS: Although most of responders perceived the Korean diagnostic
      guidelines for IBD, there were differences between recommendations of guidelines
      and actual practice patterns. Therefore, the publicity and revision of diagnostic
      guidelines are important to reconcile theory and practice.

PMID- 23172278
TI  - [Clinical significance of the large intestinal wall thickening detected by
      abdominal computed tomography].
AB  - BACKGROUND/AIMS: Bowel wall thickening on CT has been reported to reflect
      colorectal carcinoma and colitis. The aim of this study was to evaluate the
      clinical significance of the large intestinal wall thickening on CT. METHODS:
      Between January 2006 and August 2010, medical records of 815 patients who
      underwent endoscopy after CT scans within 1 month were reviewed retrospectively.
      RESULTS: A total of 233 patients were included. The wall thickening was actually
      associated with abnormal endoscopic findings in 81.1% of the cases. The accuracy
      rate on diagnosis between CT and endoscopy was 63.5%. The discrepancy in
      diagnosis was higher in cases with left colon abnormality and short segment
      lesion. Abdominal pain was significantly more common in cases suspected
      malignancy on CT compared with colitis (p=0.047). Most of the malignancy
      diagnosed on CT involved the left side colon and most of the colitis involved the
      entire colon (p<0.001). The length of lesion was below 5 cm in 86.5% of the
      malignancy. Malignancy was more common in patients aged over 50 years with
      hemoglobin below 12 g/dL. The CT findings significantly suggestive of malignancy
      were lymph node enlargement and length of lesion below 5 cm (p=0.027 and
      p<0.001). CONCLUSIONS: The large intestinal wall thickening on CT was limited in
      the differential diagnosis of malignancy and colitis. Additional endoscopic
      evaluation is needed in patients with bowel wall thickening associated with lymph
      node enlargement and short segment lesion on CT in order to exclude malignancy.

PMID- 23172279
TI  - [Efficacy of peginterferon and ribavirin combination therapy of chronic hepatitis
      C: a pooled analysis].
AB  - BACKGROUND/AIMS: A combination of peginterferon and ribavirin is the standard
      therapy for chronic hepatitis C (CHC). However, the respective study has not been
      carried out in a large scale in Korea. The purpose of this study was to collect
      the studies that have been reported in Korea in order to analyze the therapeutic
      effect of combination therapy and compare to find racial difference. METHODS:
      Twenty-eight papers related to the therapeutic effect of combination therapy in
      CHC patients were analyzed based on pooled analysis. RESULTS: Based on the
      analysis for genotype 1 in Korea, early virologic response (EVR), end of
      treatment response (ETR), and sustained virologic response (SVR) were 79.6%
      (125/157), 80.1% (166/207), and 62.7% (341/543). The EVR, ETR, and SVR for
      genotype 2 and 3 were 89.4% (119/133), 92.2% (203/220), and 84.1% (434/516). Data
      from other Asians showed that EVR and SVR for genotype 1 were 88.9% (290/326) and
      64.4% (491/762) respectively and 88.8% (135/152), and 79.4% (151/190) for
      genotype 2 and 3 respectively. In Western, EVR and SVR for genotype 1 were 51.3%
      (1,981/3,860) and 42.4% (1,798/4,231) respectively, and for genotype 2 and 3 were
      87.7% (350/399) and 77.8% (533/685) respectively. Based on the comparative
      analysis, no statistical difference in SVR between Koreans and other Asians
      (p=0.955) was observed; However, the SVR of Koreans was higher with significance
      than that of Westerns (p<0.001) On the other hand, there was no difference what
      so ever, in SVR for genotype 2 amongst the different races. CONCLUSIONS: The SVR
      of combination therapy for the Korean chronic hepatitis C patients was similar to
      other Asians but higher than Westerns.

PMID- 23172280
TI  - [A case of gastric emphysema in anorexia nervosa presenting as acute gastric
      distension].
AB  - Gas within the gastric wall is an alarming finding and a rare condition.
      Clinically, this condition is divided into two entities; Gastric emphysema and
      emphysematous gastritis. These two diseases should be differentiated because they
      are characterized by different clinical symptoms, possible etiology, treatment
      and prognosis. While emphysematous gastritis is a severe condition with high
      mortality, gastric emphysema is asymptomatic and usually has benign course.
      Rarely, anorexia nervosa and bulimia nervosa have been discribed to be associated
      with acute gastric distension and duodenal obstruction induced by superior
      mesentery artery syndrome. So, gastric emphysema could be accompanied by acute
      gastric distension induced by anorexia nervosa. We report a rare case of gastric
      emphysema in a patient with anorexia nervosa presenting as superior mesenteric
      artery syndrome with relevant literatures. In this case, the gastric emphysema
      was improved without surgical intervention after nasogastric tube for
      decompression and feeding insertion in the fourth portion of the duodenum.

PMID- 23172281
TI  - [A case of acute lymphoblastic leukemia presenting with protein-losing
      enteropathy].
AB  - Protein-losing enteropathy (PLE) is a syndrome characterized by excessive
      gastrointestinal protein loss, resulting in hypoproteinemia and edema. A variety
      of benign and malignant conditions can be associated with PLE and acute leukemia
      is a very rare cause of PLE. We report a case of PLE associated with acute
      lymphoblastic leukemia. A 27-year-old man was admitted due to watery diarrhea,
      epigastric pain and bilateral leg edema. Laboratory findings showed
      hypoproteinemia and polycythemia. The diagnosis of PLE and acute lymphoblastic
      leukemia were confirmed on the measurement of fecal a1-antitrypsin clearance and
      bone marrow examination. After systemic chemotherapy and autologous stem cell
      transplantation, his clinical symptoms and abnormal laboratory findings were
      gradually improved.

PMID- 23172282
TI  - [A case of colonic collision tumor (adenocarcinoma and neuroendocrine
      carcinoma)].
AB  - Collision tumors of the colon are rare. A 54-year-old man was referred to our
      hospital for the evaluation of hematochezia. Colonoscopy demonstrated the
      presence of about 3 cm sized mass in the rectosigmoid junction. After surgical
      resection, the colonic lesion was histologically composed of two discrete
      lesions: adenocarcinoma in the superficial layer and poorly differentiated
      neuroendocrine carcinoma in the deeper layer. We report this case of colonic
      collision tumor (adenocarcinoma and neuroendocrine carcinoma) with a review of
      the literature.

PMID- 23172283
TI  - [A case of steroid-induced hyperinfective strongyloidiasis with bacterial
      meningitis].
AB  - Strongyloides stercoralis is a soil transmitted intestinal nematode that is
      endemic in the tropical and subtropical regions. In most individuals who are
      infected, chronic, usually asymptomatic, gastrointestinal infection persists.
      But, in immunocompromized hosts or in patients receiving immunosuppressive
      therapy, autoinfection of S. stercoralis may result in the dissemination of
      larvae, leading to fatal hyperinfection and increased rate of complications. We
      report a case of hyperinfective strongyloidiasis with bacterial meningitis in a
      patient receiving steroid therapy. Strongyloidiasis was diagnosed by the presence
      of filariform larvae of S. stercoralis in the bronchoalveolar lavage cytology and
      upper gastrointestinal endoscopic biopsy specimen. Her clinical symptoms had
      progressively aggravated and developed bacterial meningitis during treatment. She
      died despite aggressive antibiotic and antihelminthic therapy.

PMID- 23172284
TI  - An insight into the hybridization mechanism of hairpin DNA physically immobilized
      on chemically modified graphenes.
AB  - There is an emerging interest in developing electrochemical DNA biosensors which
      rely on label-free protocols for the detection of DNA hybridization and
      polymorphism. Lately, many of them have been using DNA probes which were
      physically adsorbed onto different graphene platforms. In these works, the
      biorecognition event is monitored by electrochemical impedance spectroscopy and
      the detection mechanism proposed needs verification by orthogonal methods. Here,
      we aim to provide an insight into the mechanism behind the impedimetric signal
      change upon the hybridization event on graphene platforms. For this aim, we used
      an orthogonal electrochemical method, differential pulse voltammetry, to examine
      the oxidation of guanine on target DNA molecules hybridized with an inosine
      substituted hairpin DNA probe. We show that the successful biorecognition event
      leads to desorption of dsDNA from graphenic surfaces on a wide range of graphenic
      surfaces, such as graphene oxide, electrochemically reduced graphene oxide and
      thermally reduced graphene oxide. These results confirm the previous hypothesis
      based on electrochemical impedance spectroscopy data. In addition, these findings
      also have a profound impact on the understanding of both the interactions between
      DNA and graphene platforms and the DNA recognition event on graphene platforms
      for the construction of biosensors.

PMID- 23172286
TI  - WDDD: Worm Developmental Dynamics Database.
AB  - During animal development, cells undergo dynamic changes in position and gene
      expression. A collection of quantitative information about morphological dynamics
      under a wide variety of gene perturbations would provide a rich resource for
      understanding the molecular mechanisms of development. Here, we created a
      database, the Worm Developmental Dynamics Database
      (http://so.qbic.riken.jp/wddd/), which stores a collection of quantitative
      information about cell division dynamics in early Caenorhabditis elegans embryos
      with single genes silenced by RNA-mediated interference. The information contains
      the three-dimensional coordinate values of the outlines of nuclear regions and
      the dynamics of the outlines over time. The database provides free access to 50
      sets of quantitative data for wild-type embryos and 136 sets of quantitative data
      for RNA-mediated interference embryos corresponding to 72 of the 97 essential
      embryonic genes on chromosome III. The database also provides sets of four
      dimensional differential interference contrast microscopy images on which the
      quantitative data were based. The database will provide a novel opportunity for
      the development of computational methods to obtain fresh insights into the
      mechanisms of development. The quantitative information and microscopy images can
      be synchronously viewed through a web browser, which is designed for easy access
      by experimental biologists.

PMID- 23172285
TI  - The interactions of GW182 proteins with PABP and deadenylases are required for
      both translational repression and degradation of miRNA targets.
AB  - Animal miRNAs silence the expression of mRNA targets through translational
      repression, deadenylation and subsequent mRNA degradation. Silencing requires
      association of miRNAs with an Argonaute protein and a GW182 family protein. In
      turn, GW182 proteins interact with poly(A)-binding protein (PABP) and the PAN2
      PAN3 and CCR4-NOT deadenylase complexes. These interactions are required for the
      deadenylation and decay of miRNA targets. Recent studies have indicated that
      miRNAs repress translation before inducing target deadenylation and decay;
      however, whether translational repression and deadenylation are coupled or
      represent independent repressive mechanisms is unclear. Another remaining
      question is whether translational repression also requires GW182 proteins to
      interact with both PABP and deadenylases. To address these questions, we
      characterized the interaction of Drosophila melanogaster GW182 with deadenylases
      and defined the minimal requirements for a functional GW182 protein. Functional
      assays in D. melanogaster and human cells indicate that miRNA-mediated
      translational repression and degradation are mechanistically linked and are
      triggered through the interactions of GW182 proteins with PABP and deadenylases.

PMID- 23172287
TI  - PhosPhAt goes kinases--searchable protein kinase target information in the plant
      phosphorylation site database PhosPhAt.
AB  - Reversible phosphorylation is a key mechanism for regulating protein function.
      Thus it is of high interest to know which kinase can phosphorylate which
      proteins. Comprehensive information about phosphorylation sites in Arabidopsis
      proteins is hosted within the PhosPhAt database (http://phosphat.mpimp
      golm.mpg.de). However, our knowledge of the kinases that phosphorylate those
      sites is dispersed throughout the literature and very difficult to access,
      particularly for investigators seeking to interpret large scale and high
      throughput experiments. Therefore, we aimed to compile information on kinase
      substrate interactions and kinase-specific regulatory information and make this
      available via a new functionality embedded in PhosPhAt. Our approach involved
      systematic surveying of the literature for regulatory information on the members
      of the major kinase families in Arabidopsis thaliana, such as CDPKs, MPK(KK)s,
      AGC kinases and SnRKs, as well as individual kinases from other families. To
      date, we have researched more than 4450 kinase-related publications, which
      collectively contain information on about 289 kinases. Users can now query the
      PhosPhAt database not only for experimental and predicted phosphorylation sites
      of individual proteins, but also for known substrates for a given kinase or
      kinase family. Further developments include addition of new phosphorylation sites
      and visualization of clustered phosphorylation events, known as phosphorylation
      hotspots.

PMID- 23172288
TI  - UUCD: a family-based database of ubiquitin and ubiquitin-like conjugation.
AB  - In this work, we developed a family-based database of UUCD
      (http://uucd.biocuckoo.org) for ubiquitin and ubiquitin-like conjugation, which
      is one of the most important post-translational modifications responsible for
      regulating a variety of cellular processes, through a similar E1 (ubiquitin
      activating enzyme)-E2 (ubiquitin-conjugating enzyme)-E3 (ubiquitin-protein
      ligase) enzyme thioester cascade. Although extensive experimental efforts have
      been taken, an integrative data resource is still not available. From the
      scientific literature, 26 E1s, 105 E2s, 1003 E3s and 148 deubiquitination enzymes
      (DUBs) were collected and classified into 1, 3, 19 and 7 families, respectively.
      To computationally characterize potential enzymes in eukaryotes, we constructed
      1, 1, 15 and 6 hidden Markov model (HMM) profiles for E1s, E2s, E3s and DUBs at
      the family level, separately. Moreover, the ortholog searches were conducted for
      E3 and DUB families without HMM profiles. Then the UUCD database was developed
      with 738 E1s, 2937 E2s, 46 631 E3s and 6647 DUBs of 70 eukaryotic species. The
      detailed annotations and classifications were also provided. The online service
      of UUCD was implemented in PHP + MySQL + JavaScript + Perl.

PMID- 23172289
TI  - DictyBase 2013: integrating multiple Dictyostelid species.
AB  - dictyBase (http://dictybase.org) is the model organism database for the social
      amoeba Dictyostelium discoideum. This contribution provides an update on
      dictyBase that has been previously presented. During the past 3 years, dictyBase
      has taken significant strides toward becoming a genome portal for the whole
      Amoebozoa clade. In its latest release, dictyBase has scaled up to host multiple
      Dictyostelids, including Dictyostelium purpureum [Sucgang, Kuo, Tian, Salerno,
      Parikh, Feasley, Dalin, Tu, Huang, Barry et al.(2011) (Comparative genomics of
      the social amoebae Dictyostelium discoideum and Dictyostelium purpureum. Genome
      Biol., 12, R20)], Dictyostelium fasciculatum and Polysphondylium pallidum
      [Heidel, Lawal, Felder, Schilde, Helps, Tunggal, Rivero, John, Schleicher,
      Eichinger et al. (2011) (Phylogeny-wide analysis of social amoeba genomes
      highlights ancient origins for complex intercellular communication. Genome Res.,
      21, 1882-1891)]. The new release includes a new Genome Browser with RNAseq
      expression, interspecies Basic Local Alignment Search Tool alignments and a
      unified Basic Local Alignment Search Tool search for cross-species comparisons.

PMID- 23172290
TI  - Activity-regulated RNA editing in select neuronal subfields in hippocampus.
AB  - RNA editing by adensosine deaminases is a widespread mechanism to alter genetic
      information in metazoa. In addition to modifications in non-coding regions,
      editing contributes to diversification of protein function, in analogy to
      alternative splicing. However, although splicing programs respond to external
      signals, facilitating fine tuning and homeostasis of cellular functions, a
      similar regulation has not been described for RNA editing. Here, we show that the
      AMPA receptor R/G editing site is dynamically regulated in the hippocampus in
      response to activity. These changes are bi-directional, reversible and correlate
      with levels of the editase Adar2. This regulation is observed in the CA1
      hippocampal subfield but not in CA3 and is thus subfield/celltype-specific.
      Moreover, alternative splicing of the flip/flop cassette downstream of the R/G
      site is closely linked to the editing state, which is regulated by Ca(2+). Our
      data show that A-to-I RNA editing has the capacity to tune protein function in
      response to external stimuli.

PMID- 23172291
TI  - Steric antisense inhibition of AMPA receptor Q/R editing reveals tight coupling
      to intronic editing sites and splicing.
AB  - Adenosine-to-Inosine (A-to-I) RNA editing is a post-transcriptional mechanism,
      evolved to diversify the transcriptome in metazoa. In addition to wide-spread
      editing in non-coding regions protein recoding by RNA editing allows for fine
      tuning of protein function. Functional consequences are only known for some
      editing sites and the combinatorial effect between multiple sites (functional
      epistasis) is currently unclear. Similarly, the interplay between RNA editing and
      splicing, which impacts on post-transcriptional gene regulation, has not been
      resolved. Here, we describe a versatile antisense approach, which will aid
      resolving these open questions. We have developed and characterized morpholino
      oligos targeting the most efficiently edited site--the AMPA receptor GluA2 Q/R
      site. We show that inhibition of editing closely correlates with intronic editing
      efficiency, which is linked to splicing efficiency. In addition to providing a
      versatile tool our data underscore the unique efficiency of a physiologically
      pivotal editing site.

PMID- 23172292
TI  - De novo expression of neurokinin-1 receptors by spinoparabrachial lamina I
      pyramidal neurons following a peripheral nerve lesion.
AB  - Lamina I of the spinal dorsal horn is a major site of integration and
      transmission to higher centers of nociceptive information from the periphery. One
      important primary afferent population that transmits such information to the
      spinal cord expresses substance P (SP). These fibers terminate in contact with
      lamina I projection neurons that express the SP receptor, also known as the
      neurokinin-1 receptor (NK-1r). Three types of lamina I projection neurons have
      been described: multipolar, fusiform, and pyramidal. Most neurons of the first
      two types are thought to be nociceptive and express the NK-1r, whereas most
      pyramidal neurons are nonnociceptive and do not express the NK-1r. In this
      immunocytochemical and behavioral study, we induced a neuropathic pain-like
      condition in the rat by means of a polyethylene cuff placed around in the sciatic
      nerve. We document that this lesion led to a de novo expression of NK-1r on
      pyramidal neurons as well as a significant increase in SP-immunoreactive
      innervation onto these neurons. These phenotypic changes were evident at the time
      of onset of neuropathic pain-related behavior. Additionally, we show that, after
      a noxious stimulus (intradermal capsaicin injection), these NK-1r on pyramidal
      neurons were internalized, providing evidence that these neurons become
      responsive to peripheral noxious stimulation. We suggest that the changes
      following nerve lesion in the phenotype and innervation pattern of pyramidal
      neurons are of significance for neuropathic pain and/or limb temperature
      regulation.

PMID- 23172302
TI  - Proprotein convertase furin enhances survival and migration of vascular smooth
      muscle cells via processing of pro-nerve growth factor.
AB  - Maturation of nerve growth factor (NGF) in neuronal cells requires
      endoproteolytic processing of the precursor protein proNGF to beta-NGF by the
      proprotein convertase furin. Pro- and beta-NGF elicit opposite biological
      functions by differential neurotrophin-receptor binding, leading to apoptosis via
      sortilin or survival via neurotrophic tyrosine kinase receptor type-1 (TrkA),
      respectively. The present study was done to investigate the impact of furin
      dependent proNGF processing on vascular smooth muscle cell (VSMC) function. We
      found that beta-NGF mRNA and protein expression was upregulated in platelet
      derived growth factor-BB/transforming growth factor-beta1-stimulated,
      proliferating rat aortic VSMCs. Although beta-NGF itself did not affect VSMC
      proliferation, it promoted VSMC motility in an autocrine fashion via TrkA/Akt
      dependent integrin inside-out signalling. The beta-NGF-induced migration of VSMCs
      required proNGF processing by furin, which was co-regulated with NGF. Furin
      inhibition increased proNGF and reduced beta-NGF secretion, leading to apoptosis
      rather than migration. In line with our in vitro demonstration, we found co- and
      upregulation of NGF, its convertase furin and its high-affinity receptor TrkA in
      the neointima of balloon-injured rodent arteries. These results indicate that
      furin determines the balance between proNGF and beta-NGF in proliferating VSMCs,
      thus impacting on VSMC survival and migration and is also important in neointima
      formation.

PMID- 23172303
TI  - Vascular endothelial growth factor and its receptor system: physiological
      functions in angiogenesis and pathological roles in various diseases.
AB  - Vascular endothelial growth factors (VEGFs) belong to the platelet-derived growth
      factor supergene family, and they play central roles in the regulation of
      angiogenesis and lymphangiogenesis. VEGF-A, the major factor for angiogenesis,
      binds to two tyrosine kinase (TK) receptors, VEGFR-1 (Flt-1) and VEGFR-2 (KDR/Flk
      1), and regulates endothelial cell proliferation, migration, vascular
      permeability, secretion and other endothelial functions. VEGFR-2 exhibits a
      strong TK activity towards pro-angiogenic signals, whereas the soluble VEGFR-1
      (sFlt-1) functions as an endogenous VEGF inhibitor. sFlt-1 is abnormally
      overexpressed in the placenta of preeclampsia patients, resulting in the major
      symptoms of the disease due to abnormal trapping of VEGFs. The VEGF-VEGFR system
      is crucial for tumour angiogenesis, and anti-VEGF-VEGFR molecules are now widely
      used in the clinical field to treat cancer patients. The efficacy of these
      molecules in prolonging the overall survival of patients has been established;
      however, some cancers do not respond well and reduced tumour sensitivity to anti
      VEGF signals may occur after long-term treatment. The molecular basis of tumour
      refractoriness should be determined to improve anti-angiogenic therapy.

PMID- 23172304
TI  - P1 and P2' site mutations convert protease nexin-2 from a factor XIa inhibitor to
      a plasmin inhibitor.
AB  - The kunitz protease inhibitor domain of PN2 (PN2KPI) is a potent and specific
      inhibitor (K(i) 0.5-2 nM) of factor XIa (FXIa) and inhibits cerebrovascular
      thrombosis in mice. To determine whether the antithrombotic properties of PN2KPI
      arise from its FXIa-inhibitory activity, we have now prepared mutant forms of
      PN2KPI. Mutations at the P1 (Arg(15)) site in combination with P2' (Met(17))
      mutations profoundly affect inhibition of FXIa, plasmin, kallikrein, factor Xa
      and thrombin. The mutant proteins PN2KPI-R(15)K, -M(17)K, -R(15)K,M(17)K and 
      R(15)K,M(17)R lost inhibitory activity against FXIa (K(i) 34, 94, 3081 and 707
      nM, respectively) and kallikrein (no inhibition) and gained inhibitory activity
      against plasmin (K(i) 108, 7, 8 and 8 nM, respectively). The intravenous
      administration of rPN2KPI into mice dramatically decreased thrombus formation in
      a murine model of FeCl(3)-induced carotid injury, whereas rPN2KPI-R(15)K,M(17)K
      failed to inhibit thrombus formation. Molecular modelling studies showed that
      fine structural variations explain the observed functional differences in FXIa
      and plasmin inhibition. PN2KPI has potent antithrombotic activity due to its
      specific FXIa anticoagulant activity, whereas PN2KPI-R(15)K,M(17)K and PN2KPI
      R(15)K,M(17)R have potent antifibrinolytic (antiplasmin) activity without
      anticoagulant or antithrombotic activity.

PMID- 23172305
TI  - The formation of high-purity isocyanurate through proazaphosphatrane-catalysed
      isocyanate cyclo-trimerisation: computational insights.
AB  - Polyurethane foams are widely used materials and control of their physical
      properties is a significant challenge. Management of cyclo-trimerisation during
      the polymerisation process is vital when tailoring the mechanical properties of
      the foam. Proazaphosphatranes are known to efficiently catalyse the cyclo
      trimerisation of organic isocyanates, giving high purity isocyanurate with little
      uretdione by-product. The mechanism of this catalysis was previously unknown,
      although some zwitterionic intermediates have been identified spectroscopically.
      We have investigated a nucleophilic-catalysis reaction pathway involving
      sequential addition of methyl isocyanate to activated zwitterionic intermediates
      using density functional theory calculations. Evidence for significant
      transannulation by the proazaphosphatrane nitrogen was found for all
      intermediates, offering stabilisation of the phosphonium cation. Steric crowding
      at the proazaphosphatrane nucleophilic phosphorus gives rise to a preference for
      direct isocyanurate formation rather than via the uretdione, in sharp contrast to
      the uncatalysed system which has been found to preferentially proceed via the
      kinetic uretdione product. The investigations suggest the mechanism of
      proazaphosphatrane catalysed cyclo-oligomerisation does not proceed via the
      uretdione product, and hence why little of this impurity is observed
      experimentally.

PMID- 23172306
TI  - Insights into the activity, differential expression, mutual regulation, and
      functions of matrix metalloproteinases and a disintegrin and metalloproteinases
      in hypertension and cardiac disease.
AB  - Hypertensive cardiac disease is a major cause of death worldwide. Causative
      factors of hypertension include environmental stressors, genetic predisposition,
      and common morbidities of lipid metabolism such as obesity and diabetes. These
      factors pathologically elevate the systemic production of vasoconstrictive G
      protein-coupled receptor agonists. Pathological concentrations of these agonists
      upregulate the gene expression and proteolytic activity of matrix
      metalloproteinases (MMPs) and A disintegrin and metalloproteinases (ADAMs). Among
      the metalloproteinases that act in concert with other mediators to elevate the
      systemic blood pressure and to modulate the development of cardiovascular
      hypertrophy and fibrosis processes are MMP-2, MMP-7, ADAM-12, and ADAM-17. This
      review offers insights into the activity, differential expression, mutual
      regulation, and functions of these metalloproteinases. We further review evidence
      linking them to transcription factors, carrier proteins, and receptors for
      lipids. The emerging links between metalloproteinases and lipids are intriguing
      and suggest new therapeutic targets in hypertensive cardiac disease.

PMID- 23172307
TI  - Correlates of condom self-efficacy in an incarcerated juvenile population.
AB  - The purpose of this study was to enhance awareness of modes of HIV transmission
      and increase HIV/sexually transmitted diseases (STD) prevention efforts for
      incarcerated youth through use of an HIV/STD prevention program guided by the
      Making Proud Choices! curriculum. A convenience sample of 662 youth aged 13 to 18
      was recruited from Alabama juvenile detention facilities. Participants took part
      in three 2-hour sessions. Baseline and postintervention data were collected.
      There was no significant difference between males and females in intent to use
      condoms at baseline and postintervention. Intent to use condoms was the most
      influential predictor of condom self-efficacy. However, there was little change
      in condom self-efficacy among males and females at baseline and postintervention.

PMID- 23172308
TI  - 1p36 tumor suppression--a matter of dosage?
AB  - A broad range of human malignancies is associated with nonrandom 1p36 deletions,
      suggesting the existence of tumor suppressors encoded in this region. Evidence
      for tumor-specific inactivation of 1p36 genes in the classic "two-hit" manner is
      scarce; however, many tumor suppressors do not require complete inactivation but
      contribute to tumorigenesis by partial impairment. We discuss recent data derived
      from both human tumors and functional cancer models indicating that the 1p36
      genes CHD5, CAMTA1, KIF1B, CASZ1, and miR-34a contribute to cancer development
      when reduced in dosage by genomic copy number loss or other mechanisms. We
      explore potential interactions among these candidates and propose a model where
      heterozygous 1p36 deletion impairs oncosuppressive pathways via simultaneous
      downregulation of several dosage-dependent tumor suppressor genes.

PMID- 23172309
TI  - Why your new cancer biomarker may never work: recurrent patterns and remarkable
      diversity in biomarker failures.
AB  - Less than 1% of published cancer biomarkers actually enter clinical practice.
      Although best practices for biomarker development are published, optimistic
      investigators may not appreciate the statistical near-certainty and diverse modes
      by which the other 99% (likely including your favorite new marker) do indeed
      fail. Here, patterns of failure were abstracted for classification from
      publications and an online database detailing marker failures. Failure patterns
      formed a hierarchical logical structure, or outline, of an emerging, deeply
      complex, and arguably fascinating science of biomarker failure. A new cancer
      biomarker under development is likely to have already encountered one or more of
      the following fatal features encountered by prior markers: lack of clinical
      significance, hidden structure in the source data, a technically inadequate
      assay, inappropriate statistical methods, unmanageable domination of the data by
      normal variation, implausibility, deficiencies in the studied population or in
      the investigator system, and its disproof or abandonment for cause by others. A
      greater recognition of the science of biomarker failure and its near-complete
      ubiquity is constructive and celebrates a seemingly perpetual richness of
      biologic, technical, and philosophical complexity, the full appreciation of which
      could improve the management of scarce research resources.

PMID- 23172310
TI  - Macrophage delivery of an oncolytic virus abolishes tumor regrowth and metastasis
      after chemotherapy or irradiation.
AB  - Frontline anticancer therapies such as chemotherapy and irradiation often slow
      tumor growth, but tumor regrowth and spread to distant sites usually occurs after
      the conclusion of treatment. We recently showed that macrophages could be used to
      deliver large quantities of a hypoxia-regulated, prostate-specific oncolytic
      virus (OV) to prostate tumors. In the current study, we show that administration
      of such OV-armed macrophages 48 hours after chemotherapy (docetaxel) or tumor
      irradiation abolished the posttreatment regrowth of primary prostate tumors in
      mice and their spread to the lungs for up to 27 or 40 days, respectively. It also
      significantly increased the lifespan of tumor-bearing mice compared with those
      given docetaxel or irradiation alone. These new findings suggest that such a
      novel, macrophage-based virotherapy could be used to markedly increase the
      efficacy of chemotherapy and irradiation in patients with prostate cancer.

PMID- 23172311
TI  - Dual targeting of EGFR and HER3 with MEHD7945A overcomes acquired resistance to
      EGFR inhibitors and radiation.
AB  - EGF receptor (EGFR) inhibition is efficacious in cancer therapy, but initially
      sensitive tumors often develop resistance. In this study, we investigated the
      potential to overcome acquired resistance to EGFR inhibitors with MEHD7945A, a
      monoclonal antibody that dually targets EGFR and HER3 (ErbB3). In cancer cells
      resistant to cetuximab and erlotinib, we found that MEHD7945A, but not single
      target EGFR inhibitors, could inhibit tumor growth and cell-cycle progression in
      parallel with EGFR/HER3 signaling pathway modulation. MEHD7945A was more
      effective than a combination of cetuximab and anti-HER3 antibody at inhibiting
      both EGFR/HER3 signaling and tumor growth. In human tumor xenograft models, we
      confirmed the greater antitumor potency of MEHD7945A than cetuximab or erlotinib.
      MEHD7945A retained potent activity in tumors refractory to EGFR inhibitor alone.
      Furthermore, MEHD7945A also limited cross-resistance to radiation in EGFR
      inhibitor-resistant cells by modulating cell-cycle progression and repair
      processes that control apoptotic cell death. Taken together, our findings confirm
      an important role of compensatory HER3 signaling in the development of acquired
      resistance to EGFR inhibitors and offer preclinical proof-of-concept that
      MEHD7945A can effectively overcome EGFR inhibitor resistance.

PMID- 23172312
TI  - Resistance to irreversible EGF receptor tyrosine kinase inhibitors through a
      multistep mechanism involving the IGF1R pathway.
AB  - The clinical efficacy of EGF receptor (EGFR) kinase inhibitors gefitinib and
      erlotinib is limited by the development of drug resistance. The most common
      mechanism of drug resistance is the secondary EGFR T790M mutation. Strategies to
      overcome EGFR T790M-mediated drug resistance include the use of mutant selective
      EGFR inhibitors, including WZ4002, or the use of high concentrations of
      irreversible quinazoline EGFR inhibitors such as PF299804. In the current study,
      we develop drug-resistant versions of the EGFR-mutant PC9 cell line, which
      reproducibly develops EGFR T790M as a mechanism of drug resistance to gefitinib.
      Neither PF299804-resistant nor WZ4002-resistant clones of PC9 harbor EGFR T790M.
      Instead, they have shown activated insulin-like growth factor receptor (IGF1R)
      signaling as a result of loss of expression of IGFBP3 with the IGF1R inhibitor,
      BMS 536924, restoring EGFR inhibitor sensitivity. Intriguingly, prolonged
      exposure to either PF299804 or WZ4002 results in the emergence of a more drug
      resistant subclone that exhibits ERK activation. A MEK inhibitor, CI-1040,
      partially restores sensitivity to the EGFR/IGF1R inhibitor combination. Moreover,
      an IGF1R or MEK inhibitor used in combination with either PF299804 or WZ4002
      completely prevents the emergence of drug-resistant clones in this model system.
      Our studies suggest that more effective means of inhibiting EGFR T790M will
      prevent the emergence of this common drug resistance mechanism in EGFR-mutant non
      small cell lung cancer. However, multiple drug resistance mechanisms can still
      emerge. Preventing the emergence of drug resistance, by targeting pathways that
      become activated in resistant cancers, may be a more effective clinical strategy.

PMID- 23172314
TI  - Improved production of 3-hydroxypropionaldehyde by complex formation with
      bisulfite during biotransformation of glycerol.
AB  - 3-Hydroxypropionaldehyde (3HPA) is an important specialty chemical which can be
      produced from glycerol using resting cells of Lactobacillus reuteri. This
      biocatalytic route, however, suffers from substrate- and product-mediated loss of
      enzyme activity within 2 h of biotransformation. In order to overcome the
      inhibitory effects of 3HPA, complex formation with sodium bisulfite was
      investigated, optimized and applied for in situ capture of the aldehyde during
      biotransformation of glycerol in a fed-batch process. As a result, the activity
      of the cells was maintained for at least 18 h. The 3HPA produced per gram cell
      dry weight was increased 5.7 times compared to the batch production process, and
      2.2 times compared to fed-batch process without in situ complex formation. This
      approach may have potential for production and in situ removal of 3HPA after
      further process development.

PMID- 23172313
TI  - Engineering approaches for investigating tumor angiogenesis: exploiting the role
      of the extracellular matrix.
AB  - A major paradigm shift in cancer research is the emergence of multidisciplinary
      approaches to investigate complex cell behaviors, to elucidate regulatory
      mechanisms and to identify therapeutic targets. Recently, efforts are focused on
      the engineering of complex in vitro models, which more accurately recapitulate
      the growth and progression of cancer. These strategies have proven vital for
      investigating and targeting the events that control tumor angiogenesis. In this
      review, we explore how the emerging engineering approaches are being used to
      unlock the complex mechanisms regulating tumor angiogenesis. Emphasis is placed
      on models using natural and synthetic biomaterials to generate scaffolds
      mimicking the extracellular matrix, which is known to play a critical role in
      angiogenesis. While the models presented in this review are revolutionary,
      improvements are still necessary and concepts for advancing and perfecting
      engineering approaches for modeling tumor angiogenesis are proposed. Overall, the
      marriage between disparate scientific fields is expected to yield significant
      improvements in our understanding and treatment of cancer.

PMID- 23172315
TI  - Rare earth metal bis(silylamide) complexes bearing pyridyl-functionalized indenyl
      ligand: synthesis, structure and performance in the living polymerization of L
      lactide and rac-lactide.
AB  - Amine elimination of rare earth tris(silylamide) complexes
      Ln[N(SiHMe(2))(2)](3)(THF)(2) (Ln = La, Sm, Er, Lu) with 1 equiv. of the pyridyl
      functionalized indenyl ligand C(9)H(7)CMe(2)CH(2)C(5)H(4)N-alpha afforded a
      series of neutral mono-indenyl-ligated rare earth metal bis(silylamide) complexes
      (C(9)H(6)CMe(2)CH(2)C(5)H(4)N-alpha)Ln[N(SiHMe(2))(2)](2) (Ln = La (1), Sm (2),
      Er (3), Lu (4)) in 83-87% isolated yields. Reaction of
      La[N(SiHMe(2))(2)](3)(THF)(2) with 2 equivalents of C(9)H(7)CMe(2)CH(2)C(5)H(4)N
      alpha provided the neutral bis(indenyl) lanthanum mono(silylamide) complex
      (C(9)H(6)CMe(2)CH(2)C(5)H(4)N-alpha)(2)LaN(SiHMe(2))(2) (5). These complexes were
      characterized by elemental analysis, FT-IR and NMR (except for 3 for the strong
      paramagnetic property of the central metal). X-ray single crystal structural
      diffraction showed that 1-4 are isostructural and the central metals are four
      coordinated by one indenyl ring, one nitrogen atom from the pendant pyridyl
      group, and two amide groups to form a distorted tetrahedral geometry; while the
      central metal in 5 is five-coordinated by two indenyl rings, two nitrogen atoms
      from the pendant pyridyl groups, and one amide group to adopt a distorted
      pyramidal geometry, if the indenyl ring is regarded as occupying an independent
      vertex. The monoanionic pyridyl-functionalized indenyl ligand is bonded to the
      central metal in eta(5)/kappa(1) constrained geometry configuration (CGC) mode. 1
      4 are highly active for the ring-opening polymerization of L-lactide and rac
      lactide. In the presence of 2 equivalents of benzyl alcohol, 1 shows high
      activity toward L-lactide and rac-lactide in a living fashion.

PMID- 23172317
TI  - Effects of background lighting and retinal illuminance on spontaneous eyeblink
      activity of human subjects in primary eye gaze.
AB  - PURPOSE: To further evaluate possible effects of lighting conditions on the
      spontaneous eyeblink rate (SEBR) of normal young adult human subjects. METHODS: A
      baseline 5 min video recording was made followed by a second recording under test
      conditions in 7 different groups of 10 subjects. These test conditions were a
      simple repeat recording under reference conditions (subjects maintaining silence,
      with gaze directed towards a target on a 2 m distant whiteboard with the
      luminance of the reflected light of 35 cd/m, recording under lower (5 cd/m),
      higher (75 cd/m) and floodlit (150 cd/m) levels, after pupil dilation with
      phenylephrine 2.5 %, after sudden increase with floodlights (to 200 cd/m), as
      compared subjects engaged in conversation. RESULTS: The overall SEBR values
      ranged from 8.4 to 15.8 eyeblinks per minute (mean 12.3 +/- 2.8 eyeblinks per
      minute). These did not significantly change with repeated assessments, no
      significant changes were seen comparing lower or higher illumination levels or
      after pupil dilation, but an increase to 20.0 +/- 4.6 eyeblinks per minute was
      seen with a sudden increase in illumination. Conversation increased SEBR to 22.2
      +/- 6.4 eyeblinks per minute. CONCLUSIONS: Spontaneous eyeblink activity in
      silence may be slightly affected by background lighting conditions, but such
      effects are notably less than SEBR changes that can occur when there is a sudden
      increase in lighting levels (as a glare stimulus) or when assessments are made
      during conversation.

PMID- 23172316
TI  - Determination of electrokinetic and hydrodynamic parameters of proteins by
      modeling their electrophoretic mobilities through the electrically charged
      spherical soft particle.
AB  - This work explores the possibility of using the electrically charged "spherical
      soft particle" (SSP) to model the electrophoretic mobility of proteins in the low
      charge regime. The general framework concerning the electrophoretic mobility of
      the SSP already presented in the literature is analyzed and discussed here in
      particular for polyampholyte-polypeptide chains. In this regard, this theory is
      applied to BSA for different protocol pH values. The physicochemical conditions
      required to model proteins as SSP from their experimentally determined
      electrophoretic mobilities are established. In particular, the protein charge
      regulation phenomenon and the SSP particle core are included to study BSA having
      isoelectric point pI ~ 5.71, within a wide range of bulk pH values. The results
      of this case study are compared with previous ones concerning the spherical
      porous particle and the spherical hard particle with occluded water. A discussion
      of chain conformations in the SSP polyampholyte layer is presented through
      estimations of the packing and friction fractal dimensions.

PMID- 23172318
TI  - The epidemiology of microbial keratitis with silicone hydrogel contact lenses.
AB  - It was widely anticipated that after the introduction of silicone hydrogel
      lenses, the risk of microbial keratitis would be lower than with hydrogel lenses
      because of the reduction in hypoxic effects on the corneal epithelium. Large
      scale epidemiological studies have confirmed that the absolute and relative risk
      of microbial keratitis is unchanged with overnight use of silicone hydrogel
      materials. The key findings include the following: (1) The risk of infection with
      30 nights of silicone hydrogel use is equivalent to 6 nights of hydrogel extended
      wear; (2) Occasional overnight lens use is associated with a greater risk than
      daily lens use; (3) The rate of vision loss due to corneal infection with
      silicone hydrogel contact lenses is similar to that seen in hydrogel lenses; (4)
      The spectrum of causative organisms is similar to that seen in hydrogel lenses,
      and the material type does not impact the corneal location of presumed microbial
      keratitis; and (5) Modifiable risk factors for infection include overnight lens
      use, the degree of exposure, failing to wash hands before lens handling, and
      storage case hygiene practice. The lack of change in the absolute risk of disease
      would suggest that exposure to large number of pathogenic organisms can overcome
      any advantages obtained from eliminating the hypoxic effects of contact lenses.
      Epidemiological studies remain important in the assessment of new materials and
      modalities. Consideration of an early adopter effect with studies involving new
      materials and modalities and further investigation of the impact of second
      generation silicone hydrogel materials is warranted.

PMID- 23172319
TI  - Incidence and epidemiologic associations of corneal infiltrates with silicone
      hydrogel contact lenses.
AB  - Contact lens-associated corneal infiltrative events (CIEs) are presumed sterile
      events that have complicated contact lens wear for more than 30 years. There is
      consistent evidence that silicone hydrogel soft contact lenses increase CIE risk
      by twofold compared with low Dk hydrogel materials. The incidence of CIEs during
      silicone hydrogel extended wear ranges from 2% to 6% for symptomatic events and
      from 6% to 25% when asymptomatic events are included. For daily wear, with
      silicone hydrogels, the incidence of CIEs ranges from 2% to 3% for symptomatic
      events and from 7% to 20% when asymptomatic events are included. Despite the
      increased rate of CIEs with silicone hydrogels, the benefits of these lenses
      largely outweigh this risk for many patients. Most risk factors for CIEs observed
      with silicone hydrogels are consistent with CIE risk factors reported earlier
      with hydrogel lenses, such as bacterial bioburden on lens surfaces, and young age
      among others. Limiting the transfer of bacterial bioburden from the skin to
      lenses, lens cases and eventually to the eye is an obvious step forward for the
      prevention of CIEs across all lens types.

PMID- 23172320
TI  - Functional impact of tibial malrotation following intramedullary nailing of
      tibial shaft fractures.
AB  - BACKGROUND: Tibial malrotation is a complication that is seen in approximately
      30% of patients following locked intramedullary nailing. In this cohort study, we
      evaluated the hypothesis that tibial malrotation would lead to impaired
      functional outcomes. METHODS: Patients with a unilateral tibial shaft fracture
      who were managed with intramedullary nailing between 2003 and 2007 were
      identified with use of ICD-10 (International Classification of Diseases, 10th
      Revision) codes. After institutional review board approval and written informed
      consent had been obtained, specific assessment of eligible patients was achieved
      with use of computed tomography, functional measures (Lower Extremity Functional
      Scale, Olerud-Molander Score, six-minute walk test), and physical examination.
      Measures were compared between patients with and without tibial malrotation
      (defined as tibial rotation of >= 10 degrees ) on imaging studies. RESULTS: Of
      the 288 patients who were identified, 100 were eligible for the study and seventy
      consented to participate. The mean duration of follow-up (and standard deviation)
      for these seventy patients was 58 +/- 11 months. Twenty-nine patients (41%) had
      tibial malrotation. Lower Extremity Functional Scale scores were similar between
      the groups with and without malrotation (mean, 70.8 +/- 8.6 points compared with
      72.6 +/- 8.7 points; p = 0.41). The results for the other functional tests were
      also similar. CONCLUSIONS: Despite high rates of tibial malrotation following
      locked intramedullary nailing of isolated tibial diaphyseal fractures, this
      finding does not have a significant intermediate-term functional impact.

PMID- 23172321
TI  - Ultrasound-guided interscalene block anesthesia for shoulder arthroscopy: a
      prospective study of 1319 patients.
AB  - BACKGROUND: Ultrasound guidance improves the localization of anesthetic placement
      during regional anesthesia, but a decreased rate of adverse events has not been
      demonstrated in the current literature. In this large prospective study, we
      evaluated the safety, efficacy, and patient satisfaction associated with
      ultrasound-guided interscalene block. METHODS: A cohort of 1319 patients
      undergoing arthroscopic shoulder surgery at an outpatient surgery center was
      prospectively evaluated. Interscalene blocks were performed by experienced
      anesthesiologists and trainees with use of ultrasound guidance. Patients were
      queried by a physician twenty-four hours postoperatively regarding their
      satisfaction with the interscalene block and were screened for a comprehensive
      register of minor and major adverse events. Individuals with adverse events were
      followed until symptoms resolved. RESULTS: Interscalene block was ultimately
      successful in 99.6% of the cases. A total of thirty-eight adverse events
      (prevalence, 2.88%) were noted. At the time of the latest follow-up, permanent
      sequelae were present in three patients (0.23%), all of whom had relevant
      comorbidities. With regard to patient satisfaction, 99.06% of the respondents
      were "satisfied" or "very satisfied" with the interscalene block, whereas 0.94%
      of respondents were unsatisfied. In addition, 97.8% of the patients stated that
      they would elect to have an interscalene block again in the future. CONCLUSIONS:
      The present study supports the use of ultrasound-guided interscalene block by
      trained anesthesiologists for well-screened patients undergoing shoulder
      arthroscopy, given the high rate of patient satisfaction and the low rate of
      adverse events.

PMID- 23172322
TI  - Risk factors for wound complications after ankle fracture surgery.
AB  - BACKGROUND: The overall rate of complications after ankle fracture fixation
      varies between 5% and 40% depending on the population investigated, and wound
      complications have been reported to occur in 1.4% to 18.8% of patients. Large
      studies have focused on complications in terms of readmission, but few studies
      have examined risk factors for wound-related issues in the outpatient setting in
      a large number of patients. A review was performed to identify risk factors for
      wound complications tracked in the hospital and outpatient setting. METHODS: Four
      hundred and seventy-eight patients underwent open reduction and internal fixation
      of an ankle fracture between 2003 and 2010 by a single surgeon at a single
      institution. Demographic characteristics, time to surgery, comorbidities, and
      postoperative care were tracked. Wound complications were defined as those
      requiring dressing care and oral antibiotics or requiring further surgical
      treatment. RESULTS: Of the 478 patients who were followed, six (1.25%) had wounds
      requiring surgical debridement. Fourteen patients (2.9%) required further
      dressing care or a course of oral antibiotics. There were significant
      associations between wound complications and a history of diabetes (p < 0.001),
      peripheral neuropathy (p = 0.003), wound-compromising medications (p = 0.011),
      open fractures (p = 0.05), and postoperative noncompliance (p = 0.027). There was
      a significant difference in age between patients with and without wound
      complications (p = 0.045). We did not identify a relationship between time to
      surgery and complications. CONCLUSIONS: These results highlight the difficulty of
      treating medically complex and noncompliant patient populations. With careful
      preoperative monitoring of swelling, time to surgery does not affect wound
      outcome. The failure of the patient to adhere to postoperative instructions
      should be a concern to the treating surgeon.

PMID- 23172323
TI  - Do traction radiographs of distal radial fractures influence fracture
      characterization and treatment?
AB  - BACKGROUND: Our center evaluates all distal radial fractures with traction
      radiographs before splinting. Although investigations of various imaging
      modalities to evaluate distal radial fractures have been presented in the
      literature, to our knowledge the use of traction radiographs has not been well
      described. We hypothesized that the addition of traction radiographs to standard
      radiographs increases interobserver and intraobserver reliability for injury
      descriptions, affects the choice of treatment plan, and decreases the perceived
      need for computed tomography. METHODS: Radiographs for fifty consecutive eligible
      patients with distal radial fractures that were treated at a level-1 trauma
      center were used to create two image sets for each patient. Set 1 included injury
      and splint radiographs, and Set 2 included the images from Set 1 plus traction
      radiographs. The image sets were stripped of all demographic data and were
      presented in random order to seven fellowship-trained orthopaedic surgeons. The
      surgeons independently reviewed each of the 100 image sets and answered ten
      questions regarding the description and treatment of the injury. Analyses were
      conducted with kappa statistics to evaluate interobserver reliability.
      Intraobserver variability was assessed with the McNemar test after adjusting for
      clustering. RESULTS: Traction radiographs improved interobserver reliability for
      four of ten questions. With regard to intraobserver variability, responses to two
      questions were significantly changed. With the addition of traction radiographs,
      the observation of intra-articular fragments requiring reduction increased from
      38.3% to 53.1% (p < 0.05) and the perceived need to order computed tomography for
      further evaluation decreased from 21.7% to 5.1% (p < 0.001). No other changes
      reached significance. CONCLUSION: The addition of traction radiographs appeared
      to affect surgeons' interobserver reliability in the evaluation of distal radial
      fractures. In addition, traction radiographs changed the rate of detection of
      intra-articular fragments requiring reduction and the perceived need for computed
      tomography. These data indicate that traction radiographs may provide some of the
      same information as computed tomographic scans at a lower cost and argue for
      additional research comparing computed tomographic scans and traction radiographs
      of the distal part of the radius.

PMID- 23172324
TI  - Improved healing of large segmental defects in the rat femur by reverse
      dynamization in the presence of bone morphogenetic protein-2.
AB  - BACKGROUND: Large segmental defects in bone do not heal well and present clinical
      challenges. This study investigated modulation of the mechanical environment as a
      means of improving bone healing in the presence of bone morphogenetic protein
      (BMP)-2. Although the influence of mechanical forces on the healing of fractures
      is well established, no previous studies, to our knowledge, have described their
      influence on the healing of large segmental defects. We hypothesized that bone
      healing would be improved by initial, low-stiffness fixation of the defect,
      followed by high-stiffness fixation during the healing process. We call this
      reverse dynamization. METHODS: A rat model of a critical-sized femoral defect was
      used. External fixators were constructed to provide different degrees of
      stiffness and, importantly, the ability to change stiffness during the healing
      process in vivo. Healing of the critical-sized defects was initiated by the
      implantation of 11 MUg of recombinant human BMP (rhBMP)-2 on a collagen sponge.
      Groups of rats receiving BMP-2 were allowed to heal with low, medium, and high
      stiffness fixators, as well as under conditions of reverse dynamization, in which
      the stiffness was changed from low to high at two weeks. Healing was assessed at
      eight weeks with use of radiographs, histological analysis, microcomputed
      tomography, dual x-ray absorptiometry, and mechanical testing. RESULTS: Under
      constant stiffness, the low-stiffness fixator produced the best healing after
      eight weeks. However, reverse dynamization provided considerable improvement,
      resulting in a marked acceleration of the healing process by all of the criteria
      of this study. The histological data suggest that this was the result of
      intramembranous, rather than endochondral, ossification. CONCLUSIONS: Reverse
      dynamization accelerated healing in the presence of BMP-2 in the rat femur and is
      worthy of further investigation as a means of improving the healing of large
      segmental bone defects. CLINICAL RELEVANCE: These data provide the basis of a
      novel, simple, and inexpensive way to improve the healing of critical-sized
      defects in long bones. Reverse dynamization may also be applicable to other
      circumstances in which bone-healing is problematic.

PMID- 23172325
TI  - Prognostic factors for bacterial cultures positive for Propionibacterium acnes
      and other organisms in a large series of revision shoulder arthroplasties
      performed for stiffness, pain, or loosening.
AB  - BACKGROUND: Propionibacterium acnes has been grown on culture in half of the
      reported cases of chronic infection associated with shoulder arthroplasty. The
      presence of this organism can be overlooked because its subtle presentation may
      not suggest the need for culture or because, in contrast to many orthopaedic
      infections, multiple tissue samples and weeks of culture incubation are often
      necessary to recover this organism. Surgical decisions regarding implant revision
      and antibiotic therapy must be made before the results of intraoperative cultures
      are known. In the present study, we sought clinically relevant prognostic
      evidence that could help to guide treatment decisions. METHODS: We statistically
      correlated preoperative and intraoperative observations on 193 shoulder
      arthroplasty revisions that were performed because of pain, loosening, or
      stiffness with the results of a Propionibacterium acnes-specific culture
      protocol. Regression models were used to identify factors predictive of a
      positive culture for Propionibacterium acnes. RESULTS: One hundred and eight of
      the 193 revision arthroplasties were associated with positive cultures; 70% of
      the positive cultures demonstrated growth of Propionibacterium acnes. The rate of
      positive cultures per shoulder increased with the number of culture specimens
      obtained from each shoulder. Fifty-five percent of the positive cultures required
      observation for more than one week. Male sex, humeral osteolysis, and cloudy
      fluid were each associated with significant increases of >= 600% in the
      likelihood of obtaining a positive Propionibacterium acnes culture. Humeral
      loosening, glenoid wear, and membrane formation were associated with significant
      increases of >300% in the likelihood of obtaining a positive Propionibacterium
      acnes culture. CONCLUSIONS: Preoperative and intraoperative factors can be used
      to help to predict the risk of a positive culture for Propionibacterium acnes.
      This evidence is clinically relevant to decisions regarding prosthesis removal or
      retention and the need for immediate antibiotic therapy at the time of revision
      shoulder arthroplasty before the culture results become available. LEVEL OF
      EVIDENCE: Prognostic Level II. See Instructions for Authors for a complete
      description of levels of evidence.

PMID- 23172326
TI  - The effect of collagen nerve conduits filled with collagen-glycosaminoglycan
      matrix on peripheral motor nerve regeneration in a rat model.
AB  - BACKGROUND: Bioabsorbable unfilled synthetic nerve conduits have been used in the
      reconstruction of small segmental nerve defects with variable results, especially
      in motor nerves. We hypothesized that providing a synthetic mimic of the Schwann
      cell basal lamina in the form of a collagen-glycosaminoglycan (GAG) matrix would
      improve the bridging of the nerve gap and functional motor recovery. METHODS: A
      unilateral 10-mm sciatic nerve defect was created in eighty-eight male Lewis
      rats. Animals were randomly divided into four experimental groups: repair with
      reversed autograft, reconstruction with collagen nerve conduit (1.5-mm NeuraGen,
      Integra LifeSciences), reconstruction with collagen nerve conduit filled with
      collagen matrix, and reconstruction with collagen nerve conduit filled with
      collagen-GAG (chondroitin-6-sulfate) matrix. Nerve regeneration was evaluated at
      twelve weeks on the basis of the compound muscle action potential, maximum
      isometric tetanic force, and wet muscle weight of the tibialis anterior muscle,
      the ankle contracture angle, and nerve histomorphometry. RESULTS: The use of
      autograft resulted in significantly better motor recovery compared with the other
      experimental methods. Conduit filled with collagen-GAG matrix demonstrated
      superior results compared with empty conduit or conduit filled with collagen
      matrix with respect to all experimental parameters. Axon counts in the conduit
      filled with collagen-GAG matrix were not significantly different from those in
      the reversed autograft at twelve weeks after repair. CONCLUSIONS: The addition of
      the synthetic collagen basal-lamina matrix with chondroitin-6-sulfate into the
      lumen of an entubulation repair significantly improved bridging of the nerve gap
      and functional motor recovery in a rat model. CLINICAL RELEVANCE: Use of a nerve
      conduit filled with collagen-GAG matrix to bridge a motor or mixed nerve defect
      may result in superior functional motor recovery compared with commercially
      available empty collagen conduit. However, nerve autograft remains the gold
      standard for reconstruction of a segmental motor nerve defect.

PMID- 23172327
TI  - Reconstruction of the medial patellofemoral ligament was effective for traumatic
      patellar dislocation.

PMID- 23172328
TI  - A delayed physical therapy protocol that limited passive range of motion was
      similar to a protocol with early passive range of motion after rotator cuff
      repair.

PMID- 23172329
TI  - Large (36 or 40-mm) femoral heads decreased the rate of dislocation after
      revision total hip arthroplasty.

PMID- 23172330
TI  - What's New in Orthopaedic Rehabilitation.

PMID- 23172331
TI  - Long-term follow-up of shoulder hemiarthroplasty for glenohumeral osteoarthritis.
AB  - BACKGROUND: There is major controversy surrounding the use of hemiarthroplasty as
      compared with total shoulder arthroplasty for glenohumeral osteoarthritis, and
      long-term clinical outcomes of hemiarthroplasty are lacking. METHODS: Of a cohort
      of thirty patients (thirty-one shoulders) who were treated with hemiarthroplasty
      for glenohumeral osteoarthritis and followed longitudinally at our institution,
      twenty-five were available for long-term follow-up; five died, and one refused to
      participate. Three of the five patients who died had revision arthroplasty before
      death, and the data from those three were therefore included in the final follow
      up (final follow-up data therefore included twenty-seven patients and twenty
      eight shoulders). Follow-up through phone conversations and postal mail surveys
      included the following: Short Form-36, American Shoulder and Elbow Surgeons
      (ASES) shoulder outcome score, EuroQol, Simple Shoulder Test, modified Neer
      Score, and a unique, validated self-administered range-of-motion questionnaire.
      Correlations between clinical outcome and age, type of glenoid wear, and cause of
      osteoarthritis were determined. RESULTS: The average follow-up was 17.2 years
      (range, thirteen to twenty-one years). There were eight revisions (three of
      fifteen shoulders with concentric glenoids, and five of sixteen shoulders with
      eccentric glenoids). For those shoulders not revised, the average ASES score was
      70.54 (range, 36.67 to 91.67). Overall, active shoulder forward elevation and
      external rotation with the arm at 90 degrees  of abduction increased from 104
      degrees  preoperatively to 141.8 degrees  (range, 45 degrees  to 180 degrees )
      and 20.7 degrees  to 61.0 degrees  (range, 30 degrees  to 90 degrees ),
      respectively (p < 0.05), at the time of final follow-up. Of those who required
      revision arthroplasty, the average patient age at the time of the index procedure
      was 51.0 years (range, twenty-six to eighty-one years), while those not requiring
      revision averaged 57.1 years (range, twenty-seven to sixty-three years). The
      overall Neer satisfaction rating was 25%. The average Neer score and Neer rating
      for unrevised cases were significantly higher for concentric glenoid wear
      compared with eccentric glenoid wear (p = 0.015 and p = 0.001, respectively).
      Patients who had concentric glenoid wear had higher EuroQol scores (p = 0.020).
      The average Neer scores were 65.29 (range, forty-seven to seventy-eight) for
      primary osteoarthritis and 54.46 (range, forty to seventy-seven) for secondary
      osteoarthritis (p = 0.036). CONCLUSIONS: Only 25% of patients with glenohumeral
      osteoarthritis treated with shoulder hemiarthroplasty are satisfied with their
      outcome at an average of seventeen years after the operation. Patients with
      concentric glenoid wear and primary osteoarthritis have better outcomes than
      those with eccentric glenoid wear and secondary osteoarthritis do, but patients
      in both groups experienced deterioration of results over time. LEVEL OF EVIDENCE:
      Therapeutic Level IV. See Instructions for Authors for a complete description of
      levels of evidence.

PMID- 23172332
TI  - Malignant proximal fibular tumors: surgical management of 112 cases.
AB  - BACKGROUND: Malignant tumors of the proximal part of the fibula are rare. We
      sought to analyze the presenting characteristics, postoperative complications,
      and local recurrences of malignant tumors in the proximal part of the fibula in a
      large series of patients. METHODS: We identified 112 histologically confirmed
      malignant tumors of the proximal part of the fibula from the time period between
      1910 and 2007. The sex ratio was nearly equal (fifty-four male, fifty-eight
      female). The average age of the patients was 27.6 years, and the average follow
      up period was 5.7 years. RESULTS: Osteosarcoma (44%) was the most common
      diagnosis. Pain (86%), palpable mass (51%), and peroneal nerve symptoms (12%)
      were the most common presenting symptoms. One hundred and three (92%) of 112
      underwent curative surgical treatment. The two most common procedures were
      amputation in fifty (45%) of 112 patients and Malawer type-II resection in twenty
      four (21%) of 112 patients. Deliberative sacrifice of the peroneal nerve was
      performed in seventy-four patients (66%). Postoperative complications occurred in
      fourteen (12.5%) of 112 patients, including wound issues (ten of 112), peroneal
      nerve palsy despite nerve preservation (two of twenty-nine), and posterior tibial
      artery thrombosis (two of 112). No long-term knee instability was seen in the
      fifty-three patients who underwent resection with lateral collateral ligament
      reconstruction. Fifty-six patients (50%) developed distant metastases and twelve
      (11%) had local recurrences. CONCLUSIONS: Osteosarcomas are the most common
      malignant tumor of the proximal fibula. Complication rates are modest and long
      term knee instability was not seen in patients undergoing reconstruction of the
      lateral collateral ligament. Local recurrence following resection is not uncommon
      and metastatic dissemination is the main cause of death. This series represents
      the largest collection of such tumors for which there is extended follow-up and
      data on surgical complications.

PMID- 23172333
TI  - Outcomes of operative treatment of unstable ankle fractures: a comparison of
      metallic and biodegradable implants.
AB  - BACKGROUND: Biodegradable implants for internal fixation of ankle fractures may
      overcome some disadvantages of metallic implants, such as imaging interference
      and the potential need for additional surgery to remove the implants. The purpose
      of this study was to evaluate the outcomes after fixation of ankle fractures with
      biodegradable implants compared with metallic implants. METHODS: In this
      prospectively randomized study, 109 subjects with an ankle fracture underwent
      surgery with metallic (Group I) or biodegradable implants (Group II).
      Radiographic results were assessed by the criteria of the Klossner classification
      system and time to bone union. Clinical results were assessed with use of the
      American Orthopaedic Foot & Ankle Society (AOFAS) ankle-hindfoot scale, Short
      Musculoskeletal Function Assessment (SMFA) dysfunction index, and the SMFA bother
      index at three, six, and twelve months after surgery. RESULTS: One hundred and
      two subjects completed the study. At a mean of 19.7 months, there were no
      differences in reduction quality between the groups. The mean operative time was
      30.2 minutes in Group I and 56.4 minutes in Group II (p < 0.001). The mean time
      to bone union was 15.8 weeks in Group I and 17.6 weeks in Group II (p = 0.002).
      The mean AOFAS score was 87.5 points in Group I and 84.3 points in Group II at
      twelve months after surgery (p = 0.004). The mean SMFA dysfunction index was 8.7
      points in Group I and 10.5 points in Group II at twelve months after surgery (p =
      0.060). The mean SMFA bother index averaged 3.3 points in Group I and 4.6 points
      in Group II at twelve months after surgery (p = 0.052). No difference existed
      between the groups with regard to clinical outcomes for the subjects with an
      isolated lateral malleolar fracture. CONCLUSIONS: The outcomes after fixation of
      bimalleolar ankle fractures with biodegradable implants were inferior to those
      after fixation with metallic implants in terms of the score on the AOFAS scale
      and time to bone union. However, the difference in the final AOFAS score between
      the groups may not be clinically important. The outcomes associated with the use
      of biodegradable implants for the fixation of isolated lateral malleolar
      fractures were comparable with those for metallic implants.

PMID- 23172334
TI  - Lower-extremity peripheral nerve blocks in the perioperative pain management of
      orthopaedic patients: AAOS exhibit selection.
AB  - BACKGROUND: The utilization of peripheral nerve blocks in orthopaedic surgery has
      paralleled the rise in the number of ambulatory surgical procedures performed.
      Optimization of pain control in the perioperative orthopaedic patient contributes
      to improved patient satisfaction, early mobilization, decreased length of
      hospitalization, and decreased associated hospital and patient costs. Our purpose
      was to provide a concise, pertinent review of the use of peripheral nerve blocks
      in various orthopaedic procedures of the lower extremity, with specific focus on
      procedural anatomy, indications, patient outcome measures, and complications.
      METHODS: We reviewed the literature and reference textbooks on commonly performed
      lower-extremity peripheral nerve block procedures in orthopaedic surgery,
      focusing on those most commonly used. RESULTS: The use of lower-extremity
      peripheral nerve blocks is a safe and effective approach to perioperative pain
      management. Different techniques and timing can have an important impact on
      patient satisfaction, and each technique has specific indications and
      complications. For major hip surgery, one of the most commonly used is the lumbar
      plexus block, which can result in early mobilization, reduced postoperative pain,
      and decreased opioid-associated adverse events. Associated complications include
      epidural spread of anesthesia, retroperitoneal hematoma formation, and
      postoperative falls. For arthroscopic and open knee procedures, the femoral nerve
      block is frequently used adjunctively. It provides improved early postoperative
      pain control, early mobilization with therapy, and increased patient satisfaction
      compared with intra-articular or intravenous opioids alone; it also provides cost
      savings. However, some studies have shown no significant difference in outcome
      measures compared with intra-articular opioids alone for arthroscopic anterior
      cruciate ligament reconstruction. Associated complications include nerve injury,
      intravascular injection, and postoperative falls. CONCLUSIONS: The use of
      peripheral nerve blocks in lower-extremity surgery is becoming a mainstay of
      perioperative pain management strategy.

PMID- 23172338
TI  - Rapid antibiotic susceptibility testing by tracking single cell growth in a
      microfluidic agarose channel system.
AB  - Sepsis is one of the major causes of death in the US, necessitating rapid
      treatment with proper antibiotics. Conventional systems for antibiotic
      susceptibility testing (AST) take far too long (16-24 h) for the timely treatment
      of sepsis. This is because they rely on measuring optical density, which relates
      to bacterial growth, to determine the minimal inhibitory concentrations (MICs) of
      relevant antibiotics. Thus, there is a desperate need for more improved and rapid
      AST (RAST) systems. The RAST system can also reduce the growing number of
      clinical problems that are associated with antibiotic resistance caused by
      methicillin-resistant Staphylococcus aureus, vancomycin-resistant Staphylococcus
      aureus, and vancomycin-resistant enterococci. In this study, we demonstrate a
      microfluidic agarose channel (MAC) system that reduces the AST assay time for
      determining MICs by single bacterial time lapse imaging. The MAC system
      immobilizes bacteria by using agarose in a microfluidic culture chamber so that
      single cell growth can be tracked by microscopy. Time lapse images of single
      bacterial cells under different antibiotic culture conditions were analyzed by
      image processing to determine MICs. Three standard bacteria from the Clinical and
      Laboratory Standard Institute (CLSI) were tested with several kinds of
      antibiotics. MIC values that were well matched with those of the CLSI were
      obtained within only 3-4 h. We expect that the MAC system can offer rapid
      diagnosis of sepsis and thus, more efficient and proper medication in the
      clinical setting.

PMID- 23172339
TI  - 3D confocal Raman imaging of endothelial cells and vascular wall: perspectives in
      analytical spectroscopy of biomedical research.
AB  - Raman imaging was used to illustrate heterogeneity of a single endothelial cell
      and the vascular wall sample. The spectral analysis allowed for exploring the
      complexity of the studied systems in three dimensions and defining the size,
      volume, shape and biochemical composition of cellular organelles. The ability to
      construct the 3D maps by a method that does not disrupt the spatial integrity of
      the cell provided a unique insight into biochemical architecture and cellular
      processes of endothelium and vascular wall. 3D Raman imaging may be considered as
      a new trend in analytical spectroscopy to be applied in biomedical research. This
      method has a potential to be used for medical imaging and diagnostic purposes
      together with other, already established, imaging techniques.

PMID- 23172340
TI  - Developments in the field of HIV estimates: methods, parameters and trends.

PMID- 23172341
TI  - Updates to the Spectrum/Estimation and Projection Package (EPP) model to estimate
      HIV trends for adults and children.
AB  - BACKGROUND: The Spectrum and Estimation and Projection Package (EPP) programs are
      used to estimate key HIV indicators based on HIV surveillance and surveys,
      programme statistics and epidemic patterns. These indicators include the number
      of people living with HIV, new infections, AIDS deaths, AIDS orphans, the number
      of adults and children needing treatment, the need for preventing mother to child
      transmission (PMTCT) and the impact of antiretroviral treatment on survival.
      METHODS: The Joint United Nations Programme on HIV and AIDS (UNAIDS) Reference
      Group on Estimates, Models and Projections regularly reviews new data and
      information needs and recommends updates to the methodology and assumptions used
      in Spectrum. The latest updates described here were used in the 2011 round of
      global estimates. RESULTS: Spectrum and EPP have now been combined into one
      software package to enhance ease of use and ensure consistent data and
      assumptions for the curve fitting and indicator estimations. Major enhancements
      to the methods include a new adult model that tracks the HIV+ population by CD4
      count; new patterns describing child survival by time of infection (perinatally,
      <6 months, 7-12 months and 12+ months after birth); a more detailed estimate of
      mother-to-child transmission that includes differential transmission rates by CD4
      count of the mother, the effects of incident infections and new prophylaxis
      options; and new procedures to estimate uncertainty ranges around regional
      estimates. CONCLUSIONS: The revised model and software facilitate the preparation
      of new HIV estimates and use new data to address emerging needs for better
      information on need for treatment among adults and children.

PMID- 23172342
TI  - National HIV prevalence estimates for sub-Saharan Africa: controlling selection
      bias with Heckman-type selection models.
AB  - OBJECTIVES: Population-based HIV testing surveys have become central to deriving
      estimates of national HIV prevalence in sub-Saharan Africa. However, limited
      participation in these surveys can lead to selection bias. We control for
      selection bias in national HIV prevalence estimates using a novel approach, which
      unlike conventional imputation can account for selection on unobserved factors.
      METHODS: For 12 Demographic and Health Surveys conducted from 2001 to 2009 (N=138
      300), we predict HIV status among those missing a valid HIV test with Heckman
      type selection models, which allow for correlation between infection status and
      participation in survey HIV testing. We compare these estimates with conventional
      ones and introduce a simulation procedure that incorporates regression model
      parameter uncertainty into confidence intervals. RESULTS: Selection model point
      estimates of national HIV prevalence were greater than unadjusted estimates for
      10 of 12 surveys for men and 11 of 12 surveys for women, and were also greater
      than the majority of estimates obtained from conventional imputation, with
      significantly higher HIV prevalence estimates for men in Cote d'Ivoire 2005, Mali
      2006 and Zambia 2007. Accounting for selective non-participation yielded 95%
      confidence intervals around HIV prevalence estimates that are wider than those
      obtained with conventional imputation by an average factor of 4.5. CONCLUSIONS:
      Our analysis indicates that national HIV prevalence estimates for many countries
      in sub-Saharan African are more uncertain than previously thought, and may be
      underestimated in several cases, underscoring the need for increasing
      participation in HIV surveys. Heckman-type selection models should be included in
      the set of tools used for routine estimation of HIV prevalence.

PMID- 23172343
TI  - Analysis of duration of risk behaviour for key populations: a literature review.
AB  - BACKGROUND: The objective of this paper is to review literature in order to
      calculate regional estimates of the average duration of time individuals maintain
      a specific high-risk behaviour. METHODS: The review targeted the key populations
      of female sex workers (FSW), male clients of female sex workers (MCFSW), people
      who inject drugs (injecting drug users (IDU)) and high-risk men who have sex with
      men (MSM). To be included in the review the study had to provide information on
      (1) the time a person spent at risk until death or cessation of the risk
      behaviour, (2) the percentage of the sample who initiated the risk behaviour in
      less than a year or (3) the mean or median duration of the behaviour from a
      representative sample. RESULTS: 49 papers were found for the FSW population
      describing the period of time FSW stay in sex work to be between 2.9 years (Asia)
      and 12 years (Latin America). Eight papers were found for MCFSW showing the
      duration of the risk behaviour in this category varying from 4.6 years in Africa
      to 32 years in Asia. 86 papers were reviewed for the population of IDU showing
      that the average time a person injects illegal drugs varies from 5.6 years
      (Africa) to 21 years (South America). No information was found for duration of
      high-risk behaviour among MSM; instead, the definitions found in the literature
      for high- and low-risk behaviour among MSM were described. CONCLUSIONS: There is
      high variability of estimates of duration of high-risk behaviours at regional
      level. More research is needed to inform models and prevention programmes on the
      average duration of time individuals maintain a specific high-risk behaviour.

PMID- 23172344
TI  - Estimated mortality of adult HIV-infected patients starting treatment with
      combination antiretroviral therapy.
AB  - OBJECTIVE: To provide estimates of mortality among HIV-infected patients starting
      combination antiretroviral therapy. METHODS: We report on the death rates from
      122 925 adult HIV-infected patients aged 15 years or older from East, Southern
      and West Africa, Asia Pacific and Latin America. We use two methods to adjust for
      biases in mortality estimation resulting from loss from follow-up, based on
      double-sampling methods applied to patient outreach (Kenya) and linkage with
      vital registries (South Africa), and apply these to mortality estimates in the
      other three regions. Age, gender and CD4 count at the initiation of therapy were
      the factors considered as predictors of mortality at 6, 12, 24 and >24 months
      after the start of treatment. RESULTS: Patient mortality was high during the
      first 6 months after therapy for all patient subgroups and exceeded 40 per 100
      patient years among patients who started treatment at low CD4 count. This trend
      was seen regardless of region, demographic or disease-related risk factor.
      Mortality was under-reported by up to or exceeding 100% when comparing estimates
      obtained from passive monitoring of patient vital status. CONCLUSIONS: Despite
      advances in antiretroviral treatment coverage many patients start treatment at
      very low CD4 counts and experience significant mortality during the first 6
      months after treatment initiation. Active patient tracing and linkage with vital
      registries are critical in adjusting estimates of mortality, particularly in low-
      and middle-income settings.

PMID- 23172345
TI  - Estimates of peripartum and postnatal mother-to-child transmission probabilities
      of HIV for use in Spectrum and other population-based models.
AB  - BACKGROUND: The Global Plan Towards the Elimination of New HIV Infections among
      Children and Keeping Their Mothers Alive aims to reduce by 2015 the number of new
      infections in children, in 22 priority countries, by at least 90% from 2009
      levels. Mathematical models, such as Spectrum, are used to estimate national and
      global trends of the number of infants infected through mother-to-child
      transmission (MTCT). However, other modelling exercises have also examined MTCT
      under different settings. MTCT probabilities applied in models to populations
      that are assumed to receive antiretroviral interventions need to reflect the most
      current risk estimates. METHODS: The UNAIDS Reference Group on Estimates,
      Modelling and Projections held a consultation to review data on MTCT
      probabilities. Published literature, recent conferences and data from personal
      communications with principle investigators were reviewed. Based on available
      data, peripartum and postnatal transmission probabilities were estimated for
      different antiretroviral drug regimens and maternal CD4 levels including for
      women with incident infection. RESULTS: Incident infections occurring during
      pregnancy are estimated to be associated with a 30% probability of MTCT; incident
      infections during breast feeding lead to a 28% probability of postnatal MTCT. The
      2010 WHO recommended regimens (Options A or B) are estimated to be associated
      with a 2% peripartum transmission probability and 0.2% transmission probability
      per month of breast feeding. Peripartum and postnatal transmission probabilities
      were lowest for women who were taking antiretroviral therapy before the pregnancy
      namely 0.5% peripartum and 0.16% per month of breast feeding, respectively.
      DISCUSSION: These updated probabilities of HIV transmission (applied to Spectrum
      in April 2011) will be used to estimate new child HIV infections and track
      progress towards the 2015 targets of the Global Plan.

PMID- 23172346
TI  - Spline-based modelling of trends in the force of HIV infection, with application
      to the UNAIDS Estimation and Projection Package.
AB  - OBJECTIVE: We previously developed a flexible specification of the UNAIDS
      Estimation and Projection Package (EPP) that relied on splines to generate time
      varying values for the force of infection parameter. Here, we test the
      feasibility of this approach for concentrated HIV/AIDS epidemics with very sparse
      data and compare two methods for making short-term future projections with the
      spline-based model. METHODS: Penalised B-splines are used to model the average
      infection risk over time within the EPP 2011 modelling framework, which includes
      antiretroviral treatment effects and CD4 cell count progression, and is fit to
      sentinel surveillance prevalence data with a Bayesian algorithm. We compare two
      approaches for future projections: (1) an informative prior related to
      equilibrium prevalence and (2) a random walk formulation. RESULTS: The spline
      based model produced plausible fits across a range of epidemics, which included
      87 subpopulations from 14 countries with concentrated epidemics and 75
      subpopulations from 33 countries with generalised epidemics. The equilibrium
      prior and random walk approaches to future projections yielded similar prevalence
      estimates, and both performed well in tests of out-of-sample predictive validity
      for prevalence. In contrast, in some cases the two approaches varied
      substantially in estimates of incidence, with the random walk formulation
      avoiding extreme changes in incidence. CONCLUSIONS: A spline-based approach to
      allowing the force of infection parameter to vary over time within EPP 2011 is
      robust across a diverse array of epidemics, including concentrated ones with
      limited surveillance data. Future work on the EPP model should consider the
      impact that different modelling approaches have on estimates of HIV incidence.

PMID- 23172347
TI  - Trends in HIV prevalence among young people in generalised epidemics:
      implications for monitoring the HIV epidemic.
AB  - BACKGROUND: Countries measure trends in HIV incidence to assess the impact of HIV
      prevention and treatment programmes. Most countries have approximated trends in
      HIV incidence through modelled estimates or through trends in HIV prevalence
      among young people (aged 15-24 years) assuming they have recently become sexually
      active and have thus only been recently exposed to HIV. METHODS: Trends in HIV
      incidence are described and results are compared using three proxy measures of
      incidence: HIV prevalence among young women attending antenatal clinics (ANCs) in
      22 countries; HIV prevalence among young male and female nationally
      representative household survey respondents in 14 countries; and modelled
      estimates of adult (ages 15-49 years) HIV incidence in 26 countries. The
      significance of changes in prevalence among ANC attendees and young survey
      respondents is tested. RESULTS: Among 26 countries, 25 had evidence of some
      decline in HIV incidence and 15 showed statistically significant declines in
      either ANC data or survey data. Only in Mozambique did the direction of the trend
      in young ANC attendees differ from modelled adult incidence, and in Mali and
      Zambia trends among young men differed from trends in adult incidence. The
      magnitude of change differed by method. CONCLUSIONS: Trends in HIV prevalence
      among young people show encouraging declines. Changes in fertility patterns, HIV
      infected children surviving to adulthood, and participation bias could affect
      future proxy measures of incidence trends.

PMID- 23172349
TI  - Identifying and quantifying misclassified and under-reported AIDS deaths in
      Brazil: a retrospective analysis from 1985 to 2009.
AB  - BACKGROUND: A retrospective analysis of deaths registered in the Brazilian
      Mortality System was conducted to quantify the under-reporting of HIV/AIDS deaths
      and those misclassified to AIDS-related conditions in the 15-49 years old
      population in Brazil. METHODS: Death rates for AIDS-related diseases were
      calculated by age and sex for 1985-2009. Changes in the age-sex-specific death
      rates over time were used to identify conditions likely to be misclassified AIDS
      deaths and to quantify the corresponding number of misclassified deaths. Deaths
      due to ill-defined causes were redistributed across all other natural causes of
      death. The resulting total number of AIDS deaths was further adjusted for
      incompleteness of the mortality reporting system. RESULTS: Out of the 28
      potential causes of death investigated, five increased in the same distinct age
      pattern as AIDS: pneumonia, Kaposi's sarcoma, other immunodeficiencies, other
      septicaemia and toxoplasmosis. 18 490 deaths due to these five causes were
      recoded to HIV/AIDS from 1985 to 2009. 38 145 deaths due to ill-defined causes
      were redistributed to AIDS and 15 485 were added to the number of AIDS deaths to
      correct for completeness of the mortality system in Brazil. Altogether, 72 120
      deaths were recoded to AIDS between 1985 and 2009 and added to the reported 194
      445 AIDS related deaths in the country, representing 27% misclassification of
      AIDS deaths in Brazil. CONCLUSIONS: This study demonstrated that AIDS mortality
      is underestimated by the official mortality information system in Brazil. Efforts
      need to be made to reduce misclassification of causes of death in the future and
      identify ways in which the confidentiality of information regarding cause of
      death can be maintained.

PMID- 23172350
TI  - A comparison of respondent-driven and venue-based sampling of female sex workers
      in Liuzhou, China.
AB  - OBJECTIVES: To compare two methods for sampling female sex workers (FSWs) for bio
      behavioural surveillance. We compared the populations of sex workers recruited by
      the venue-based Priorities for Local AIDS Control Efforts (PLACE) method and a
      concurrently implemented network-based sampling method, respondent-driven
      sampling (RDS), in Liuzhou, China. METHODS: For the PLACE protocol, all female
      workers at a stratified random sample of venues identified as places where people
      meet new sexual partners were interviewed and tested for syphilis. Female workers
      who reported sex work in the past 4 weeks were categorised as FSWs. RDS used peer
      recruitment and chain referral to obtain a sample of FSWs. Data were collected
      between October 2009 and January 2010. We compared the socio-demographic
      characteristics and the percentage with a positive syphilis test of FSWs
      recruited by PLACE and RDS. RESULTS: The prevalence of a positive syphilis test
      was 24% among FSWs recruited by PLACE and 8.5% among those recruited by RDS and
      tested (prevalence ratio 3.3; 95% CI 1.5 to 7.2). Socio-demographic
      characteristics (age, residence and monthly income) also varied by sampling
      method. PLACE recruited fewer FSWs than RDS (161 vs 583), was more labour
      intensive and had difficulty gaining access to some venues. RDS was more likely
      to recruit from areas near the RDS office and from large low prevalence
      entertainment venues. CONCLUSIONS: Surveillance protocols using different
      sampling methods can obtain different estimates of prevalence and population
      characteristics. Venue-based and network-based methods each have strengths and
      limitations reflecting differences in design and assumptions. We recommend that
      more research be conducted on measuring bias in bio-behavioural surveillance.

PMID- 23172348
TI  - Focusing the HIV response through estimating the major modes of HIV transmission:
      a multi-country analysis.
AB  - OBJECTIVE: An increasing number of countries have been estimating the
      distribution of new adult HIV infections by modes of transmission (MOT) to help
      prioritise prevention efforts. We compare results from studies conducted between
      2008 and 2012 and discuss their use for planning and responding to the HIV
      epidemic. METHODS: The UNAIDS recommended MOT model helps countries to estimate
      the proportion of new HIV infections that occur through key transmission modes
      including sex work, injecting drug use (IDU), men having sex with men (MSM),
      multiple sexual partnerships, stable relationships and medical interventions. The
      model typically forms part of a country-led process that includes a comprehensive
      review of epidemiological data. Recent revisions to the model are described.
      RESULTS: Modelling results from 25 countries show large variation between and
      within regions. In sub-Saharan Africa, new infections occur largely in the
      general heterosexual population because of multiple partnerships or in stable
      discordant relationships, while sex work contributes significantly to new
      infections in West Africa. IDU and sex work are the main contributors to new
      infections in the Middle East and North Africa, with MSM the main contributor in
      Latin America. Patterns vary substantially between countries in Eastern Europe
      and Asia in terms of the relative contribution of sex work, MSM, IDU and spousal
      transmission. CONCLUSIONS: The MOT modelling results, comprehensive review and
      critical assessment of data in a country can contribute to a more strategically
      focused HIV response. To strengthen this type of research, improved
      epidemiological and behavioural data by risk population are needed.

PMID- 23172353
TI  - Transport and function of chloride in vascular smooth muscles.
AB  - This review summarizes the current knowledge of Cl(-) transport in vascular
      smooth muscle cells (VSMCs). VSMCs accumulate Cl(-) intracellularly using two
      secondary-active transport mechanisms. The Cl(-) equilibrium potential is more
      positive than the resting membrane potential enabling Cl(-) to be a depolarizing
      ion upon activation of a Cl(-) conductance. Cl(-) currents are involved in
      different vascular responses suggesting a number of different Cl(-) channels. All
      known Cl(-) channel families, with the exception of the GABA-/glycine-receptor
      family, have been identified in VSMCs. At least one member of the voltage
      activated ClC family - ClC-3 - has been suggested to be involved in myogenic
      constriction, in cell proliferation and to have an anti-apoptotic action. The
      cystic fibrosis transmembrane conductance regulator is also demonstrated in
      VSMCs. The molecular identity of the major anion conductance in VSMCs - a Ca(2+)
      activated Cl(-) current - is uncertain. Several candidates have been suggested
      with bestrophin and TMEM16 protein families the current favorites. Specific
      pharmacological tools are lacking for Cl(-) channels but recent molecular biology
      developments have made selective gene manipulations possible. A continuing quest
      within the vascular research field is to explicitly demonstrate the coupling
      between a putative channel protein and an endogenous Cl(-) current and the
      importance of these for specific functions.

PMID- 23172351
TI  - Expression of the plant viral protease NIa in the brain of a mouse model of
      Alzheimer's disease mitigates Abeta pathology and improves cognitive function.
AB  - The plant viral protease, NIa, has a strict substrate specificity for the
      consensus sequence of Val-Xaa-His-Gln, with a scissoring property after Gln. We
      recently reported that NIa efficiently cleaved the amyloid-beta (Abeta) peptide,
      which contains the sequence Val-His-His-Gln in the vicinity of the cleavage site
      by alpha-secretase, and that the expression of NIa using a lentiviral system in
      the brain of AD mouse model reduced plaque deposition levels. In the present
      study, we investigated whether exogenous expression of NIa in the brain of AD
      mouse model is beneficial to the improvement of cognitive deficits. To address
      this question, Lenti-NIa was intracerebrally injected into the brain of Tg
      APPswe/ PS1dE9 (Tg-APP/PS1) mice at 7 months of age and behavioral tests were
      performed 15-30 days afterwards. The results of the water maze test indicated
      that Tg-APP/PS1 mice which had been injected with Lenti-GFP showed an increased
      latency in finding the hidden-platform and markedly enhanced navigation near the
      maze-wall, and that such behavioral deficits were significantly reversed in Tg
      APP/PS1 mice injected with Lenti-NIa. In the passive avoidance test, Tg-APP/PS1
      mice exhibited a severe deficit in their contextual memory retention, which was
      reversed by NIa expression. In the marble burying test, Tg-APP/PS1 mice buried
      marbles fewer than non-transgenic mice, which was also significantly improved by
      NIa. After behavioral tests, it was verified that the Tg-APP/PS1 mice with Lenti
      NIa injection had reduced Abeta levels and plaque deposition when compared to Tg
      APP/PS1 mice. These results showed that the plant viral protease, NIa, not only
      reduces Abeta pathology, but also improves behavioral deficits.

PMID- 23172354
TI  - pH-tuned metal coordination and peroxidase activity of a peptide dendrimer enzyme
      model with a Fe(II)bipyridine at its core.
AB  - Peptide dendrimer BP1 was obtained by double thioether bond formation between
      5,5'-bis(bromomethyl)-2,2'-bipyridine and two equivalents of peptide dendrimer N1
      (Ac-Glu-Ser)(8)(Dap-Glu-Ala)(4)(Dap-Amb-Tyr)(2)Dap-Cys-Asp-NH(2) (Dap = branching
      2,3-diaminopropanoic acid, Amb = 4-aminomethyl-benzoic acid). At pH 4.0 BP1 bound
      Fe(ii) to form the expected tris-coordinated complex [Fe(II)(BP1)(3)] (K(f) = 2.1
      * 10(15) M(-3)). At pH 6.5 a monocoordinated complex [Fe(II)(BP1)] was formed
      instead (K(f) = 2.1 * 10(5) M(-1)) due to electrostatic repulsion between the
      polyanionic dendrimer branches, as confirmed by the behavior of three analogues
      where glutamates were partially or completely replaced by neutral glutamines or
      positive lysines. [Fe(II)(BP1)] catalyzed the oxidation of o-phenylenediamine
      with H(2)O(2) with enzyme-like kinetics (k(cat) = 1.0 min(-1), K(M) = 1.5 mM,
      k(cat)/k(uncat) = 90 000) and multiple turnover, while Fe(2+) or
      [Fe(bipy)(3)](2+) were inactive. The labile coordination positions allowing
      coordination to H(2)O(2) and to the substrate are likely responsible for the
      enhanced peroxidase activity of the metallopeptide dendrimer.

PMID- 23172355
TI  - Fiber alignment directs cell motility over chemotactic gradients.
AB  - The ability of tissue engineered scaffolds to direct cell behavior is paramount
      for scaffold design. Cell migration can be directed by various methods including
      chemical, adhesive, mechanical, and topographical cues. Electrospinning has
      emerged as a popular method to control topography and create fibrous scaffolds
      similar to that found in extracellular matrix. One major hurdle is limited cell
      infiltration and several studies have explored methods to alter electrospun
      materials to increase scaffold porosity; however, uniform cell distributions
      within scaffolds is still limited. Towards this, we investigated the motility of
      HUVECs on a model system of electrospun hyaluronic acid fibers under a gradient
      of VEGF and found that topographical cues dominate cell motility direction. Using
      time-lapse microscopy, cell aspect ratio, and migration angle were measured;
      cells were directed in a chemical gradient and/or on aligned electrospun fibers.
      Measurements of the persistence time demonstrated an additive effect of the
      chemical gradient and fiber alignment. However, when fibers were aligned
      perpendicular to a chemical gradient, cells were directed by fiber alignment and
      there was no effect of the chemical gradient. These results suggest that
      topographical cues may be more influential than chemical cues in directing cell
      motility and should be considered in material design.

PMID- 23172357
TI  - Fixed drug eruption caused by  fluconazole: a case report and  mini-review of the
      literature.

PMID- 23172358
TI  - Histamine H1-receptor antagonistic drug olopatadine suppresses TSLP in atopic
      dermatitis model mice.

PMID- 23172359
TI  - Therapeutic effects of beta1, 4 mannobiose in a Balb/c mouse model of
      intranasally-induced pollen allergy.
AB  - BACKGROUND: Nutritional prebiotic supplementation represents an attractive
      approach for interventions of allergy. In this study, the potential therapeutic
      effect of beta-1, 4 mannobiose (MNB) in a murine model of cedar pollinosis was
      investigated. METHODS: Groups of Balb/c mice were intranasally sensitized to
      Japanese cedar pollen extract, and subsequently administered with low or high
      dose MNB. Both intraperitoneal and intranasal challenges were performed to
      monitor for clinical signs. Frequency of sneezing was recorded. Serum, spleen and
      Peyer's patches were collected for various biomarker analyses. Anti-allergic
      activity of MNB using RBL-2H3 cells was also evaluated. RESULTS: Significant
      decrease in sneezing frequency, histamine, interleukin (IL)-4 and IL-17A and
      increase in TGF-beta and IL-10 concentration were exhibited by the MNB-treated
      mice. However, Cry j1 and Cry j 2-specific IgE activity remained unaltered. The
      high dose MNB treatment increased total IgA activity and IL-10, TGF-beta and
      FoxP3 and decreased IL-4, IL-17A, and RORgammaT mRNA expression. Inhibition of
      activation of RBL-2H3 cells was observed via decrease in histamine, intracellular
      Ca2+ concentration, and FcepsilonRI mRNA expression. CONCLUSIONS: We demonstrated
      the immunomodulatory effects of MNB and conclude that MNB is a potential
      therapeutic molecular nutritional supplement candidate for treatment of pollen
      allergy.

PMID- 23172360
TI  - Reconstruction and analysis of the genome-scale metabolic network of Candida
      glabrata.
AB  - Candida glabrata has been recognized as an efficient industrial microorganism for
      the production of pyruvate, the most widely used alpha-oxocarboxylic acid in the
      areas of agrochemicals, drugs, and chemicals. To gain a comprehensive
      understanding of its physiology and cellular metabolism, the genome-scale
      metabolic model for C. glabrata (named iNX804), comprising 804 genes, 1287
      reactions, and 1025 metabolites, was reconstructed by genome sequence annotation
      and biochemical data mining. The flux balance analysis data of model iNX804
      exhibited good agreement with the experimental data, including the phenotypic
      data and the carbon flux distribution. The model iNX804 predicted that C.
      glabrata can synthesize a high concentration of pyruvate because it has a strong
      glucose transport capacity and three pyruvate biosynthesis pathways and is
      deficient in key steps in vitamin synthesis. Furthermore, the metabolic capacity
      of pyruvate and other fine chemicals derived from pyruvate was evaluated by in
      silico deletion and overexpression of several key genes. The metabolic model
      iNX804 provides a potential platform for global elucidation of the metabolism of
      C. glabrata.

PMID- 23172361
TI  - Controlled perturbation of the thermodynamic equilibrium by microfluidic
      separation of porphyrin-based aggregates in a multi-component self-assembling
      system.
AB  - In a microfluidic H-cell, a multi-component self-assembled system is brought out
      of-equilibrium by changing the bimodal composition of porphyrin stacks and
      pyridine-capped dimers. Driven by their different diffusivities, diffusion
      controlled separation in methylcyclohexane reveals different compositions when
      detected in-line and off-line, which demonstrates the kinetic behaviour of this
      metastable system. The microfluidic technique also proves to be highly equipped
      to determine diffusion constants of the different assemblies.

PMID- 23172362
TI  - Commentary on nutrition standards in the national school lunch and breakfast
      programs.

PMID- 23172363
TI  - Dual-cycle dielectrophoretic collection rates for probing the dielectric
      properties of nanoparticles.
AB  - A new DEP spectroscopy method and supporting theoretical model is developed to
      systematically quantify the dielectric properties of nanoparticles using
      continuously pulsed DEP collection rates. Initial DEP collection rates, that are
      dependent on the nanoparticle dielectric properties, are an attractive
      alternative to the crossover frequency method for determining dielectric
      properties. The new method introduces dual-cycle amplitude modulated and
      frequency-switched DEP (dual-cycle DEP) where the first collection rate with a
      fixed frequency acts as a control, and the second collection rate frequency is
      switched to a chosen value, such that, it can effectively probe the dielectric
      properties of the nanoparticles. The application of the control means that
      measurement variation between DEP collection experiments is reduced so that the
      frequency-switched probe collection is more effective. A mathematical model of
      the dual-cycle method is developed that simulates the temporal dynamics of the
      dual-cycle DEP nanoparticle collection system. A new statistical method is also
      developed that enables systematic bivariate fitting of the multifrequency DEP
      collection rates to the Clausius-Mossotti function, and is instrumental for
      determining dielectric properties. A Monte-Carlo simulation validates that
      collection rates improve estimation of the dielectric properties, compared with
      the crossover method, by exploiting a larger number of independent samples.
      Experiments using 200 nm diameter latex nanospheres suspended in 0.2 mS/m KCl
      buffer yield a nanoparticle conductivity of 26 mS/m that lies within 8% of the
      expected value. The results show that the dual-frequency method has considerable
      promise particularly for automated DEP investigations and associated
      technologies.

PMID- 23172364
TI  - The effects of ionic liquid on the electrochemical sensing performance of
      graphene- and carbon nanotube-based electrodes.
AB  - The electrochemical sensing properties of graphene-based and carbon nanotube
      (CNT)-based electrodes towards ascorbic acid, dopamine, uric acid, and glucose
      are systematically compared. Nano-sized Pd catalyst particles are uniformly
      dispersed on both carbon supports using a supercritical fluid deposition
      technique to increase the sensing performance. The CNT/Pd electrode shows higher
      detection current than that of the graphene/Pd electrode, which is attributed to
      the three-dimensional architecture interwoven by the CNTs that creates a larger
      number of reaction sites. With the incorporation of ionic liquid (IL), the
      detection sensitivity of the IL/graphene/Pd electrode significantly increases,
      becoming noticeably higher than that of the IL/CNT/Pd counterpart. The
      synergistic interactions between graphene and IL that lead to the superior
      sensing performance are demonstrated and discussed.

PMID- 23172365
TI  - Site-selective azide incorporation into endogenous RNase A via a "chemistry"
      approach.
AB  - Site-selective labeling of endogenous proteins represents a major challenge in
      chemical biology, mainly due to the absence of unique reactive groups that can be
      addressed selectively. Recently, we have shown that surface-exposed lysine
      residues of two endogenous proteins and a peptide exhibit subtle changes in their
      individual reactivities. This feature allows the modification of a single residue
      in a highly site-selective fashion if kinetically controlled labeling conditions
      are applied. In order to broaden the scope of the "kinetically-controlled protein
      labeling" (KPL) approach and highlight additional applications, the water-soluble
      bioorthogonal reagent, biotin-TEO-azido-NHS (11), is developed which enables the
      site-selective introduction of an azido group onto endogenous proteins/peptides.
      This bioconjugation reagent features a biotin tag for affinity purification, an
      azido group for bioorthogonal labeling, a TEO (tetraethylene oxide) linker acting
      as a spacer and to impart water solubility and an N-hydroxysuccinimidyl (NHS)
      ester group for reacting with the exposed lysine residue. As a proof of concept,
      the native protein ribonuclease A (RNase A) bearing ten available lysine residues
      at the surface is furnished with a single azido group at Lys 1 in a highly site
      selective fashion yielding azido-(K1)RNase A. The K1 site-selectivity is
      demonstrated by the combined application and interpretation of high resolution
      MALDI-ToF mass spectroscopy, tandem mass spectroscopy and extracted ion
      chromatography (XIC). Finally, the water soluble azide-reactive phosphine probe,
      rho-TEO-phosphine (21) (rho: rhodamine), has been designed and applied to attach
      a chromophore to azido-(K1)RNase A via Staudinger ligation at physiological pH
      indicating that the introduced azido group is accessible and could be addressed
      by other established azide-reactive bioorthogonal reaction schemes.

PMID- 23172368
TI  - Mitochondria "fuel" breast cancer metabolism: fifteen markers of mitochondrial
      biogenesis label epithelial cancer cells, but are excluded from adjacent stromal
      cells.
AB  - Here, we present new genetic and morphological evidence that human tumors consist
      of two distinct metabolic compartments. First, re-analysis of genome-wide
      transcriptional profiling data revealed that > 95 gene transcripts associated
      with mitochondrial biogenesis and/or mitochondrial translation were significantly
      elevated in human breast cancer cells, as compared with adjacent stromal tissue.
      Remarkably, nearly 40 of these upregulated gene transcripts were mitochondrial
      ribosomal proteins (MRPs), functionally associated with mitochondrial translation
      of protein components of the OXPHOS complex. Second, during validation by
      immunohistochemistry, we observed that antibodies directed against 15 markers of
      mitochondrial biogenesis and/or mitochondrial translation (AKAP1, GOLPH3,
      GOLPH3L, MCT1, MRPL40, MRPS7, MRPS15, MRPS22, NRF1, NRF2, PGC1-alpha, POLRMT,
      TFAM, TIMM9 and TOMM70A) selectively labeled epithelial breast cancer cells.
      These same mitochondrial markers were largely absent or excluded from adjacent
      tumor stromal cells. Finally, markers of mitochondrial lipid synthesis (GOLPH3)
      and mitochondrial translation (POLRMT) were associated with poor clinical outcome
      in human breast cancer patients. Thus, we conclude that human breast cancers
      contain two distinct metabolic compartments-a glycolytic tumor stroma, which
      surrounds oxidative epithelial cancer cells-that are mitochondria-rich. The co
      existence of these two compartments is indicative of metabolic symbiosis between
      epithelial cancer cells and their surrounding stroma. As such, epithelial breast
      cancer cells should be viewed as predatory metabolic "parasites," which undergo
      anabolic reprogramming to amplify their mitochondrial "power." This notion is
      consistent with the observation that the anti-malarial agent chloroquine may be
      an effective anticancer agent. New anticancer therapies should be developed to
      target mitochondrial biogenesis and/or mitochondrial translation in human cancer
      cells.

PMID- 23172370
TI  - Direct methane oxidation over Pt-modified nitrogen-doped carbons.
AB  - Nitrogen-doped carbons derived from biomass precursors were modified with Pt(2+)
      and successfully tested as solid catalysts in the direct oxidation of methane in
      fuming sulfuric acid. Remarkably, the catalytic performance was found to be
      substantially better than the Pt-modified Covalent Triazine Framework (CTF)
      system previously reported, although deactivation is more pronounced for the
      biomass derived catalyst supports.

PMID- 23172369
TI  - BRCA1 mutations drive oxidative stress and glycolysis in the tumor
      microenvironment: implications for breast cancer prevention with antioxidant
      therapies.
AB  - Mutations in the BRCA1 tumor suppressor gene are commonly found in hereditary
      breast cancer. Similarly, downregulation of BRCA1 protein expression is observed
      in the majority of basal-like breast cancers. Here, we set out to study the
      effects of BRCA1 mutations on oxidative stress in the tumor microenvironment. To
      mimic the breast tumor microenvironment, we utilized an in vitro co-culture model
      of human BRCA1-mutated HCC1937 breast cancer cells and hTERT-immortalized human
      fibroblasts. Notably, HCC1937 cells induce the generation of hydrogen peroxide in
      the fibroblast compartment during co-culture, which can be inhibited by genetic
      complementation with the wild-type BRCA1 gene. Importantly, treatment with
      powerful antioxidants, such as NAC and Tempol, induces apoptosis in HCC1937
      cells, suggesting that microenvironmental oxidative stress supports cancer cell
      survival. In addition, Tempol treatment increases the apoptotic rates of MDA-MB
      231 cells, which have wild-type BRCA1, but share a basal-like breast cancer
      phenotype with HCC1937 cells. MCT4 is the main exporter of L-lactate out of cells
      and is a marker for oxidative stress and glycolytic metabolism. Co-culture with
      HCC1937 cells dramatically induces MCT4 protein expression in fibroblasts, and
      this can be prevented by either BRCA1 overexpression or by pharmacological
      treatment with NAC. We next evaluated caveolin-1 (Cav-1) expression in stromal
      fibroblasts. Loss of Cav-1 is a marker of the cancer-associated fibroblast (CAF)
      phenotype, which is linked to high stromal glycolysis, and is associated with a
      poor prognosis in numerous types of human cancers, including breast cancers.
      Remarkably, HCC1937 cells induce a loss of Cav-1 in adjacent stromal cells during
      co-culture. Conversely, Cav-1 expression in fibroblasts can be rescued by
      administration of NAC or by overexpression of BRCA1 in HCC1937 cells. Notably,
      BRCA1-deficient human breast cancer samples (9 out of 10) also showed a
      glycolytic stromal phenotype, with intense mitochondrial staining specifically in
      BRCA1-deficient breast cancer cells. In summary, loss of BRCA1 function leads to
      hydrogen peroxide generation in both epithelial breast cancer cells and
      neighboring stromal fibroblasts, and promotes the onset of a reactive glycolytic
      stroma, with increased MCT4 and decreased Cav-1 expression. Importantly, these
      metabolic changes can be reversed by antioxidants, which potently induce cancer
      cell death. Thus, antioxidant therapy appears to be synthetically lethal with a
      BRCA1-deficiency in breast cancer cells and should be considered for future
      cancer prevention trials. In this regard, immunostaining with Cav-1 and MCT4
      could be used as cost-effective biomarkers to monitor the response to antioxidant
      therapy.

PMID- 23172372
TI  - Expression of miR-124 inhibits growth of medulloblastoma cells.
AB  - Medulloblastoma is the most common malignant brain tumor in children, and a
      substantial number of patients die as a result of tumor progression.
      Overexpression of CDK6 is present in approximately one-third of medulloblastomas
      and is an independent poor prognostic marker for this disease. MicroRNA (miR)-124
      inhibits expression of CDK6 and prevents proliferation of glioblastoma and
      medulloblastoma cells in vitro. We examined the effects of miR-124 overexpression
      on medulloblastoma cells both in vitro and in vivo and compared cell lines that
      have low and high CDK6 expression. MiR-124 overexpression inhibits the
      proliferation of medulloblastoma cells, and this effect is mediated mostly
      through the action of miR-124 upon CDK6. We further show that induced expression
      of miR-124 potently inhibits growth of medulloblastoma xenograft tumors in
      rodents. Further testing of miR-124 will help define the ultimate therapeutic
      potential of preclinical models of medulloblastoma in conjunction with various
      delivery strategies for treatment.

PMID- 23172371
TI  - Choroid plexus papillomas: advances in molecular biology and understanding of
      tumorigenesis.
AB  - Choroid plexus papillomas are rare, benign tumors originating from the choroid
      plexus. Although generally found within the ventricular system, they can arise
      ectopically in the brain parenchyma or disseminate throughout the neuraxis. We
      sought to review recent advances in our understanding of the molecular biology
      and oncogenic pathways associated with this disease. A comprehensive PubMed
      literature review was conducted to identify manuscripts discussing the clinical,
      molecular, and genetic features of choroid plexus papillomas. Articles concerning
      diagnosis, treatment, and long-term patient outcomes were also reviewed. The
      introduction of atypical choroid plexus papilloma as a distinct entity has
      increased the need for accurate histopathologic diagnosis. Advances in
      immunohistochemical staining have improved our ability to differentiate choroid
      plexus papillomas from other intracranial tumors or metastatic lesions using
      combinations of key markers and mitotic indices. Recent findings have implicated
      Notch3 signaling, the transcription factor TWIST1, platelet-derived growth factor
      receptor, and the tumor necrosis factor-related apoptosis-inducing ligand pathway
      in choroid plexus papilloma tumorigenesis. A combination of commonly occurring
      chromosomal duplications and deletions has also been identified. Surgical
      resection remains the standard of care, although chemotherapy and radiotherapy
      may be considered for recurrent or metastatic lesions. While generally considered
      benign, these tumors possess a complex biology that sheds insight into other
      choroid plexus tumors, particularly malignant choroid plexus carcinomas.
      Improving our understanding of the molecular biology, genetics, and oncogenic
      pathways associated with this tumor will allow for the development of targeted
      therapies and improved outcomes for patients with this disease.

PMID- 23172373
TI  - Vascular actions of aldosterone.
AB  - Aldosterone exerts direct effects on the vascular system by inducing oxidative
      stress, inflammation, hypertrophic remodeling, fibrosis, and endothelial
      dysfunction. Aldosterone exerts its effects through genomic and nongenomic
      pathways in a mineralocorticoid receptor (MR)-dependent or independent manner.
      Other aldosterone receptors such as GPR30 have been identified. A tight relation
      exists between the aldosterone and angiotensin II pathways, as well as with the
      endothelin-1 system. There is a correlation between plasma levels of aldosterone
      and cardiovascular risk. Recently, an increasing body of evidence has underlined
      the importance of aldosterone in cardiovascular complications associated with the
      metabolic syndrome, such as arterial remodeling and endothelial dysfunction.
      Blockade of MR is an increasingly used evidence-based therapy for many forms of
      cardiovascular disease, including hypertension, heart failure, chronic kidney
      disease, and diabetes mellitus.

PMID- 23172375
TI  - Results of the Cox-Maze III/IV procedure in patients over 75 years old who
      present for cardiac surgery with a history of atrial fibrillation.
AB  - AIM: Elderly patients with atrial fibrillation (AF) present a special challenge.
      Despite the documented advantage in ablating AF, the addition of the procedure
      may add complexity and potentially impact patient outcome. This study explored
      the impact of the Cox-Maze III/IV procedure on elderly patients experiencing AF
      who present for cardiac surgery. METHODS: Forty-four patients aged >= 75 with
      concomitant surgery underwent the Cox-Maze III/IV procedure for AF. These
      patients were followed using our extensive longitudinally designed registry to
      include health related quality of life (HRQL). Late death was captured by the
      Social Security Index and the National Death Index. RESULTS: The mean age for
      this sample was 79.5 +/- 3 years and mean additive euroSCORE was 9 +/- 2.1 (high
      risk). The majority of patients with the Cox-Maze procedure underwent concomitant
      valve surgery (N. = 41, 93%). There was a low incidence of STS measured
      perioperative outcomes in this group. NSR rates at six months were 90% (26/29)
      and 85% (23/27) at 12 months for the ablation group. There were no embolic
      strokes and major bleeding events occurred in only two patients. By Kaplan-Meier
      analysis, two-year cumulative survival was 89.6% and there was only one operative
      mortality in this group (2.3%). CONCLUSION: Addition of the Cox-Maze III/IV
      procedure in patients >= 75 years may add to the complexity of the surgical
      procedure, but does not increase the operative risk. Age should not be the only
      discriminating factor when considering the Cox-Maze III/IV procedure for patients
      aged >= 75 years who present for cardiac surgery while experiencing atrial
      fibrillation.

PMID- 23172374
TI  - Ikaros promotes rearrangement of TCR alpha genes in an Ikaros null thymoma cell
      line.
AB  - Ikaros is important in the development and maintenance of the lymphoid system,
      functioning in part by associating with chromatin-remodeling complexes. We have
      studied the functions of Ikaros in the transition from pre-T cell to the CD4(+)
      CD8(+)  thymocyte using an Ikaros null CD4(-) CD8(-)  mouse thymoma cell line
      (JE131). We demonstrate that this cell line carries a single functional TCR beta
      gene rearrangement and expresses a surface pre-TCR. JE131 cells also carry
      nonfunctional rearrangements on both alleles of their TCR alpha loci. Retroviral
      reintroduction of Ikaros dramatically increased the rate of transcription in the
      alpha locus and TCR Valpha/Jalpha recombination resulting in the appearance of
      many new alphabetaTCR(+)  cells. The process is RAG dependent, requires
      switch/sucrose nonfermentable chromatin-remodeling complexes and is coincident
      with the binding of Ikaros to the TCR alpha enhancer. Furthermore, knockdown of
      Mi2/nucleosome remodeling and deacetylase complexes increased the frequency of
      TCR alpha rearrangement. Our data suggest that Ikaros controls Valpha/Jalpha
      recombination in T cells by controlling access of the transcription and
      recombination machinery to the TCR alpha loci. The JE131 cell line should prove
      to be a very useful tool for studying the molecular details of this and other
      processes involved in the pre-T cell to alphabetaTCR(+)  CD4(+) CD8(+)  thymocyte
      transition.

PMID- 23172376
TI  - Females do not have increased risk of early or late mortality after isolated
      aortic valve replacement: results from a multi-institutional Australian study.
AB  - AIM: There is controversy regarding whether isolated aortic valve replacement
      (AVR) in women is associated with an increased risk of early and late mortality.
      The current study evaluates the impact of gender as an independent risk factor
      for early and late mortality after isolated AVR. METHODS: Data obtained between
      June 2001 and December 2009 by the Australasian Society of Cardiac and Thoracic
      Surgeons Cardiac Surgery Database Program was retrospectively analysed.
      Demographic, operative data and postoperative complications were compared between
      male and female patients using chi(2) and t-tests. Long-term survival analysis
      was performed using Kaplan Meier survival curves and the log rank test.
      Independent risk factors for short term and long term mortality were identified
      using binary logistic and Cox regression, respectively. RESULTS: Isolated aortic
      valve replacement was undertaken for 2790 patients in 18 Australian institutions;
      41.9% were female. Female patients were generally older (mean age 72 vs. 66 years
      (P<0.001) and presented more often with hypertension (P<0.001) and obesity
      (P<0.001). They were less likely to present with cerebrovascular disease
      (P=0.018), renal failure (P=0.017) and non-elective presentation (P=0.017). Women
      were observed to have a lower 30-day mortality (1.7% vs. 2.1%) but there was no
      difference on univariate (P=0.490) or multivariate analysis (P=0.983). There was
      no difference in the incidence of early complications but women were more likely
      to require red blood cell transfusion (P<0.001). Long-term survival was
      comparable between men and women (P=0.662). CONCLUSION: Female patients
      undergoing isolated AVR do not have an increased risk of early and late
      mortality. Further investigation is required to delineate the impact of gender on
      early and late outcomes following AVR.

PMID- 23172377
TI  - The use of N-terminal pro-brain natriuretic peptide as a predictor of atrial
      fibrillation after cardiac surgery.
AB  - AIM: Atrial fibrillation (AF) is the most common arrhythmia after cardiac surgery
      with cardiopulmonary bypass (CPB). The value of Nt-pro BNP in predicting AF
      complicating cardiac surgery is not well studied. Our objective is to determine
      its predictive role in the occurrence of this complication after heart surgery
      with cardiopulmonary bypass. METHODS: It is a prospective observational study
      including patients proposed for scheduled cardiac surgery with normo-thermal CPB.
      We performed blood samples for each patient: the first one immediately after the
      induction of anesthesia and before CPB. The following samples were made at the
      end of the CBP (H0), 4 hours later (H4) and every day during the first four days
      (H24, H48, H72 and H96). NT-proBNP and cTnI were measured in each sample. The
      postoperative AF was defined as any episode of AF documented of a period not less
      than 15 min recorded in the first 3 days post operative. RESULTS: The most common
      cardiovascular complication was the AF (17.5%). Rates of Nt-proBNP were
      significantly increased in patients who developed this complication. The ROC
      analysis of NT-proBNP at different times studied for the prediction of AF showed
      that assays at the end of the CPB and those of the 4th postoperative hour (H4)
      had the best area under the curve (AUC). A threshold value of 353.5 mg/mL of Nt
      proBNP at the end of the CPB has a sensitivity of 71% and a specificity of 84%
      for the prediction of the AF and an AUC of 0.711. The threshold value (307.5
      mg/mL) of Nt-proBNP measured at H4 has the same sensitivity but with a lower
      specificity (74%) and AUC=0.709. DISCUSSION AND CONCLUSION: An early Nt pro BNP
      at H0 or H4, respectively, and with thresholds of 353 and 307 pg/mL could predict
      the occurrence of the AF. In this case, a primary prevention could be envisaged.

PMID- 23172378
TI  - Diverse reactivity of an isolable dialkylsilylene toward imines.
AB  - The reactions of isolable dialkylsilylene 10 with various aldimines proceed
      smoothly at low temperatures to give diverse products depending on the
      substituents on the imine. The reactions of 10 with 4-XC(6)H(4)CH=NPh [X = H
      (11a), MeO (11b), and Cl (11c)] give the corresponding silaaziridines 12a-12c in
      high yields, which are thermally very stable and remain intact in the air and
      moisture for a long time. In contrast, the reactions of 10 with 4
      F(3)CC(6)H(4)CH=NPh (11d) and 3,5-(F(3)C)(2)C(6)H(3)CH=NPh (11e) having strong
      electron-withdrawing aryl substituents on imine carbon are accompanied by 1,2
      trimethylsilyl migration rather unexpectedly to give silaazetidines 13d-13e
      incorporated into a bicyclo[3.2.0]heptane ring. The reaction of 10 with N
      benzylbenzaldimine 11f affords the corresponding (dibenzylamino)silane 14f in a
      moderate yield. Molecular structures of 12a-12c, 13d-13e and 14f were determined
      by X-ray crystallography. All these reactions are proposed to occur via the
      initial formation of the corresponding imine silaylides, while the subsequent
      reactions leading to the final products are controlled by the electronic
      structure of the ylide depending on the substituents. N-phenylbenzophenimine 11g
      does not react with 10.

PMID- 23172379
TI  - Substitution effect on phenalenyl backbone in the rate of organozinc catalyzed
      ROP of cyclic esters.
AB  - A series of zinc complexes (1-6) supported by substituted phenalenyl ligands was
      synthesized by reacting the phenalenyl ligands with diethyl zinc under ethane
      evolution. The solid state structures of these complexes (1-6) were determined by
      single crystal X-ray crystallography. Furthermore, the organozinc complexes (4-6)
      were tested for the polymerization of cyclic esters as efficient catalysts for
      the ring-opening polymerization of epsilon-caprolactone (epsilon-CL) and rac
      lactide (rac-LA) in the presence of benzyl alcohol (BnOH) as initiator. Complex 4
      exhibited remarkably higher rate of polymerization under identical reaction
      condition than complexes 5 and 6. The polymerization of epsilon-caprolactone
      produced polymer with narrow polydispersities (M(w)/M(n) = 1.06 to 1.22), while
      the polymerization of lactide monomers afforded polylactides with polydispersity
      values ranging from 1.08 to 1.8. The kinetic experiments unravelled a controlled
      polymerization. The controlled nature of polymerization was further utilized in
      the preparation of the block copolymer poly(CL)block-poly(rac-LA).

PMID- 23172383
TI  - 2D difference gel electrophoresis reference map of a Fusarium graminearum
      nivalenol producing strain.
AB  - Fusarium graminearum is widely studied as a model for toxin production among
      plant pathogenic fungi. A 2D DIGE reference map for the nivalenol-producing
      strain 453 was established. Based on a whole protein extract, all reproducible
      spots were systematically picked and analyzed by MALDI-TOF/TOF, leading to the
      identification of 1102 protein species. The obtained map contributes to the
      annotation of the genome by identifying previously nondescribed hypothetical
      proteins and will serve as a reference for future studies aiming at deciphering
      F. graminearum biology and chemotype diversity.

PMID- 23172384
TI  - Different characteristic phenotypes according to antibody in myasthenia gravis.
AB  - OBJECTIVES: To find the characteristic phenotypes of 3 different types of
      myasthenia gravis (MG). METHODS: The clinical and electrophysiological features
      among 15 cases of muscle-specific kinase antibody positive (MuSK Ab+) MG, 59
      cases of double seronegative (DSN) MG, and 161 cases of acetylcholine receptor
      antibody (AChR Ab)+ MG in the University of Alabama at Birmingham were compared.
      RESULTS: AChR Ab was positive in 69% of cases and MuSK Ab in 6% of cases. MuSK
      Ab+ MG was more common (14%) in African Americans compared with whites (4%). AChR
      Ab+ MG is characterized by male predominance, later onset, a fewer cases of
      ocular MG, and a higher association with thymoma. DSN-MG is characterized by a
      greater prevalence of ocular MG, milder forms of MG with less number of crisis,
      and fewer abnormalities in the repetitive nerve stimulation test. MuSK Ab+ MG is
      characterized by younger age at onset, severe and bulbar forms of MG, predominant
      faciobulbar neck weakness, and a poor response to edrophonium,
      anticholinesterase, and intravenous immunoglobulin. Long-term outcome showed no
      difference among 3 types of MG. CONCLUSIONS: AChR Ab+ MG and DSN-MG are similar,
      with the exception of less severity in the latter. MuSK Ab+ MG has distinct
      clinical and electrophysiological features.

PMID- 23172385
TI  - Guillain-Barre syndrome after influenza vaccination in the United States, a
      report from the CDC/FDA vaccine adverse event reporting system (1990-2009).
AB  - OBJECTIVES: To determine the rate of Guillain-Barre syndrome (GBS) after
      administration of influenza vaccine in the United States and to provide further
      information about the characteristics and temporal profile of these incidents.
      METHODS: Data were acquired from the Vaccine Adverse Event Reporting System,
      supplemented by data from the Center for Biologics and Research under the Freedom
      of Information Act between 1990 and 2009. RESULTS: There were 802 cases (mean
      age, 54.72 +/- 18.4 years) of GBS reported after influenza vaccination in the
      United States between 1990 and 2009. Among the 802 vaccinated patients with
      available data, 624 (77.8%) developed GBS within 6 weeks and 78 (9.7%) after 6
      weeks, whereas these data were unavailable for the remaining 100 patients (13%).
      The reporting rate of post-influenza vaccine GBS was within the range expected in
      the general population or approximately 0.46 cases per million vaccinations. A
      non-Gaussian distribution of GBS within the first 6 weeks post-vaccination was
      noted, given that the peak incidence occurred in the second week. CONCLUSIONS:
      The incidence of post-influenza vaccine GBS is similar to the incidence of
      idiopathic GBS in the general population. Although the nonnormal distribution of
      post-vaccination GBS suggests that some cases may be triggered by vaccination,
      the greater risk of complications from influenza virus infections makes
      vaccination the first-line strategy for infection prevention and support the
      current guidelines on vaccination.

PMID- 23172386
TI  - Lower extremity predominant stiff-person syndrome and limbic encephalitis with
      amphiphysin antibodies in breast cancer.
AB  - A 54-year-old woman presented with several weeks of psychiatric symptoms, partial
      onset seizures, and painful spasms of the lower extremities. On examination, she
      exhibited severe stiffness and intermittent extensor spasms of the lower
      extremities. Magnetic resonance imaging of the brain showed T2 hyperintensity in
      the left temporal lobe with enhancement after gadolinium administration on T1
      weighted images. Amphiphysin antibodies were present in the serum. Radiographic
      screening for malignancy disclosed a metastatic breast cancer. The case is a
      unique example of amphiphysin autoimmunity, illustrating the possibility of
      paraneoplastic stiff-person syndrome and limbic encephalitis coexisting in a
      patient with a "classical" presentation of stiff-person syndrome confined to the
      lower extremities.

PMID- 23172387
TI  - Acute bilateral painless radiculitis with abnormal Borrelia burgdorferi
      immunoblot.
AB  - A 57-year-old woman with a history of hypertension and hypothyroidism presented
      with painless left arm weakness and numbness 2 weeks before evaluation. Nerve
      conduction studies of the left arm revealed normal motor and sensory responses.
      Needle examination revealed acute denervation changes in all myotomes of the
      affected extremity, including cervical paraspinals on the left, and several
      myotomes on the contralateral side. The laboratory evaluation revealed normal
      anti-GM1 antibodies and 3 IgM/5 IgG bands on Lyme Western Blot. The patient began
      treatment with 28 days of intravenous ceftriaxone. On follow-up, patient had
      regained full strength of her extremities with no sensory deficits. Inflammatory
      borrelia radiculitis usually presents with pain in the distribution of the
      affected nerves and nerve roots. The novelty of this case report rests on (1) the
      absence of primary borreliosis symptomatology preceding the radiculitis and (2)
      the painless and bilateral clinical presentation in a patient with suspected Lyme
      radiculitis.

PMID- 23172388
TI  - Camptocormia due to inclusion body myositis.
AB  - Inclusion body myositis is the most common idiopathic inflammatory myopathy in
      elderly individuals. It typically causes proximal and distal limb weakness with
      forearm flexors and quadriceps being the most severely affected muscles. Axial
      musculature is infrequently involved. Here, we report an 80-year-old man who
      presented with an 18-month history of progressive truncal weakness causing
      stooped posture while standing and walking. Neurologic examination revealed no
      limb weakness. magnetic resonance imaging studies showed atrophy and findings,
      suggesting fatty replacement of paraspinal muscles. Needle electromyography
      confirmed the presence of an axial myopathy. Thoracic paraspinal muscle biopsy
      showed canonical features of inclusion body myositis. The current patient
      broadens the clinical presentation of inclusion body myositis.

PMID- 23172389
TI  - Amyotrophic lateral sclerosis with positive anti-acetylcholine receptor
      antibodies. Case report and review of the literature.
AB  - Myasthenia gravis is a nerve-muscle junction disease, for which the most specific
      test is an increase in the anti-acetylcholine receptor antibodies (anti-AChR-Abs)
      titer. Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease
      affecting both upper and lower motor neurons. Positive AChR-Ab in patients with
      pure ALS are exceedingly rare. We report the case of a patient with confirmed ALS
      and very high levels of AChR-Ab and review the literature on this topic.

PMID- 23172390
TI  - The diagnostic utility of a commercial limb-girdle muscular dystrophy gene test
      panel.

PMID- 23172392
TI  - Theoretical estimation of drag tag lengths for direct quantitative analysis of
      multiple miRNAs (DQAMmiR).
AB  - To better understand the regulatory roles of miRNA in biological functions and to
      use miRNA as molecular markers of diseases, we need to accurately measure amounts
      of multiple miRNAs in biological samples. Direct quantitative analysis of
      multiple miRNAs (DQAMmiR) has been recently developed by using a classical
      hybridization approach where miRNAs are hybridized with fluorescently labeled
      complementary DNA probes taken in excess, and the amounts of the hybrids and the
      unreacted probes are measured to calculate the amount of miRNAs. Capillary
      electrophoresis was used as an instrumental platform for analysis. The problem of
      separating the unreacted probes from the hybrids was solved by adding SSB to the
      run buffer. A more difficult problem of separating hybrids from each other was
      solved by attaching different drag tags to the probes. Biotin and a hairpin
      forming extension on the probe were used as two drag tags in the proof-of
      principle work. Making DQAMmiR a generic approach requires a generic solution for
      drag tags. Peptides have been suggested as drag tags for long oligonucleotides in
      DNA sequencing by electrophoresis. Here we theoretically consider short peptides
      of different lengths as drag tags for DQAMmiR. We find analytical equations that
      allow us to estimate mobilities of RNA-DNA hybrids with peptide drag tags of
      different lengths. Our calculations suggest that the mobility shifts required for
      DQAMmiR can be achieved with the length of peptide chains in the ranges of 5-20
      residues for five miRNAs and 2-47 residues for nine miRNAs. Peptides of these
      lengths can be feasibly synthesized with good yield and purity. The results of
      this theoretical study will guide the design and production of hybridization
      probes for DQAMmiR.

PMID- 23172393
TI  - A nucleic acid probe labeled with desmethyl thiazole orange: a new type of
      hybridization-sensitive fluorescent oligonucleotide for live-cell RNA imaging.
AB  - A new fluorescent nucleotide with desmethyl thiazole orange dyes, D'(505), has
      been developed for expansion of the function of fluorescent probes for live-cell
      RNA imaging. The nucleoside unit of D'(505) for DNA autosynthesis was soluble in
      organic solvents, which made the preparation of nucleoside units and the
      reactions in the cycles of DNA synthesis more efficient. The dyes of D'(505)
      containing oligodeoxynucleotide were protonated below pH 7 and the
      oligodeoxynucleotide exhibited hybridization-sensitive fluorescence emission
      through the control of excitonic interactions of the dyes of D'(505). The
      simplified procedure and effective hybridization-sensitive fluorescence emission
      produced multicolored hybridization-sensitive fluorescent probes, which were
      useful for live-cell RNA imaging. The acceptor-bleaching method gave us
      information on RNA in a specific cell among many living cells.

PMID- 23172394
TI  - High-density extraction solvent-based solvent de-emulsification dispersive liquid
      liquid microextraction combined with MEKC for detection of chlorophenols in water
      samples.
AB  - For the first time, the high-density solvent-based solvent de-emulsification
      dispersive liquid-liquid microextraction (HSD-DLLME) was developed for the fast,
      simple, and efficient determination of chlorophenols in water samples followed by
      field-enhanced sample injection with reverse migrating micelles in CE. The
      extraction of chlorophenols in the aqueous sample solution was performed in the
      presence of extraction solvent (chloroform) and dispersive solvent (acetone). A
      de-emulsification solvent (ACN) was then injected into the aqueous solution to
      break up the emulsion, the obtained emulsion cleared into two phases quickly. The
      lower layer (chloroform) was collected and analyzed by field-enhanced sample
      injection with reverse migrating micelles in CE. Several important parameters
      influencing the extraction efficiency of HSD-DLLME such as the type and volume of
      extraction solvent, disperser solvent and de-emulsification solvent, sample pH,
      extraction time as well as salting-out effects were optimized. Under the
      optimized conditions, the proposed method provided a good linearity in the range
      of 0.02-4 MUg/mL, low LODs (4 ng/mL), and good repeatability of the extractions
      (RSDs below 9.3%, n = 5). And enrichment factors for three phenols were 684, 797,
      and 233, respectively. This method was then utilized to analyze two real
      environmental samples from wastewater and tap water and obtained satisfactory
      results. The obtained results indicated that the developed method is an excellent
      alternative for the routine analysis in the environmental field.

PMID- 23172395
TI  - Do obesity and sleep problems cluster in the workplace? A multivariate,
      multilevel study.
AB  - OBJECTIVES: The aim of this study was to examine the co-occurrence of obesity and
      sleep problems among employees and workplaces. METHODS: We obtained data from 39
      873 men and women working in 3040 workplaces in 2000-2002 (the Finnish Public
      Sector Study). Individual- and workplace-level characteristics were considered as
      correlates of obesity and sleep problems, which were modelled simultaneously
      using a multivariate, multilevel approach. RESULTS: Of the participants, 11% were
      obese and 23% reported sleep problems. We found a correlation between obesity and
      sleep problems at both the individual [correlation coefficient 0.048, covariance
      0.047, standard error (SE) 0.005) and workplace (correlation coefficient 0.619,
      covariance 0.068, SE 0.011) level. The latter, but not the former, correlation
      remained after adjustment for individual- and workplace-level confounders, such
      as age, sex, socioeconomic status, shift work, alcohol consumption, job strain,
      and proportion of temporary employees and manual workers at the workplace.
      CONCLUSIONS: Obese employees and those with sleep problems tend to cluster in the
      same workplaces, suggesting that, in addition to targeting individuals at risk,
      interventions to reduce obesity and sleep problems might benefit from identifying
      "risky" workplaces.

PMID- 23172396
TI  - Optimization of an oil leaching process to reduce the level of dioxins and dioxin
      like PCBs in fishmeal.
AB  - BACKGROUND: Fishmeal produced from fish caught in polluted fishing areas might
      contain dioxins and dioxin-like polychlorinated biphenyls (PCBs) above maximum
      permitted levels (MPL) for use in feed. Decontamination of the fishmeal can be
      achieved by hexane extraction. The principal objective of this study was to
      optimize a more environmentally friendly alternative based on oil leaching of the
      moist presscake intermediate product during fishmeal manufacturing. RESULTS: A
      central composite design and response surface methodology was used to study the
      influence of the process variables temperature (T), presscake moisture content
      (MC) and leaching time (LT) on the decontamination process. A significant squared
      MC effect was observed, resulting in an optimum leaching rate at 27% MC. This
      corresponds to 5% improved dibenzo-p-dioxin/dibenzo furan (PCDD/F)-PCB toxic
      equivalent (TEQ) reduction compared to normal presscake (55% MC). The initial
      leaching rate was fast, with a TEQ reduction of 69% after only 2 min at 87 
      degrees C and 55% MC. Under the best experimental conditions (87  degrees C, 38%
      MC, 12 min LT) a TEQ reduction of 82% was achieved. Excess oil in the presscake
      after the leaching operation could be removed by use of a water washing step. No
      reduction in protein quality measured by mink digestibility could be observed.
      CONCLUSION: The results confirm that the oil leaching process is robust and
      offers easily achievable TEQ levels well below present MPLs based on process
      conditions normally used by the industry. Comparative effects on non-dioxin-like
      PCBs are expected.

PMID- 23172398
TI  - Particulate mass and polycyclic aromatic hydrocarbons exposure from secondhand
      smoke in the back seat of a vehicle.
AB  - CONTEXT: Exposure to secondhand smoke (SHS) has been reduced in the USA by
      banning smoking in public places. These restrictions have not had the same effect
      on children's exposure to SHS as adults suggesting that children are exposed to
      SHS in locations not covered by bans, such as private homes and cars. OBJECTIVES:
      Assess exposure to SHS in the backseat of a stationary vehicle where a child
      would sit, quantify exposures to fine particulates (PM2.5), polycyclic aromatic
      hydrocarbons (PAH), carbon monoxide (CO) and nicotine. Estimate the impact on a
      child's mean daily exposure to PM2.5. METHODS: SHS exposures in stationary
      vehicles with two different window configurations were monitored. A volunteer
      smoked three cigarettes in a one-hour period for twenty-two experiments. PM2.5,
      CO, nicotine and PAH where measured in the backseat of the vehicle. 16 PAH
      compounds were measured for in gas and particle phases as well as real-time
      particle phase concentrations. RESULTS: The mean PAH concentration, 1325.1
      ng/m(3), was larger than concentrations measured in bars and restaurants were
      smoking is banned in many countries. We estimate that a child spending only ten
      minutes in the car with a smoker at the mean PM2.5 concentration measured in the
      first window configuration--1697 mg/m(3)--will cause a 30% increase to the daily
      mean PM2.5 personal average of a child. CONCLUSIONS: Estimates made using the
      measured data and previously reported PM2.5 daily mean concentrations for
      children in California showing that even short exposure periods are capable of
      creating large exposure to smoke.

PMID- 23172397
TI  - Altered reactivity of tertiary mesenteric arteries following acute myocardial
      ischemia.
AB  - BACKGROUND: It is unknown if cardiac ischemia has any deleterious effect on the
      contractile properties of nonischemic, peripheral vascular beds. Thus, the
      objective of the present study was to determine whether acute myocardial ischemia
      results in peripheral vascular dysfunction. METHODS AND RESULTS: This study
      characterized force maintenance and the sensitivity to acetylcholine (ACh)
      mediated smooth muscle (SM) relaxation of tertiary (3rd) mesenteric arteries from
      Sprague-Dawley rats following 30 min of myocardial ischemia. Both the
      phosphorylation of nonmuscle (NM) light chain (LC) and SM-LCs as well as the
      expression of myosin phosphatase targeting subunit 1 (MYPT1) were also
      determined. Our data demonstrate that acute myocardial ischemia resulted in
      vascular dysfunction of 3rd mesenteric vessels, characterized by decreases in
      force maintenance, ACh- and cGMP-mediated SM relaxation, the phosphorylation of
      NM-LCs and SM-LCs, and MYPT1 expression. Ischemia was also associated with an
      increase in protein polyubiquitination, suggesting that during ischemia MYPT1 is
      targeted for degradation or proteolysis. CONCLUSION: Acute myocardial ischemia
      produces peripheral vascular dysfunction; the changes in LC phosphorylation and
      MYPT1 expression result in a decrease in both tone and the sensitivity to NO
      mediated SM relaxation of the peripheral vasculature.

PMID- 23172399
TI  - Public perceptions of the ban on tobacco sales in San Francisco pharmacies.
AB  - BACKGROUND: In October, 2008, legislation was implemented in the city and county
      of San Francisco, California, prohibiting the sale of tobacco products in
      pharmacies. OBJECTIVE: To characterise public awareness and perceptions of the
      ban on tobacco sales in San Francisco community pharmacies. METHODS: A brief,
      anonymous survey was used to assess public awareness and perceptions of a ban on
      tobacco sales approximately 1 year after implementation. Individuals were
      approached by researchers outside of chain pharmacies in San Francisco. Smokers
      and non-smokers were included, and participants did not have to be patrons of the
      pharmacy. RESULTS: Of 198 participants, 56% were in favor of the ban, 27% opposed
      it and 17% were undecided. A greater proportion of current tobacco users (81%)
      than former/never users (48%) were aware of the ban (p<0.001), and a lesser
      proportion were supportive of the ban (21% of current users vs 66% of
      former/never users; p<0.001). Most current tobacco users (88% of n=43) had not
      considered quitting smoking as a result of the ban. The majority of consumers
      indicated that the ban on cigarette sales did not influence their shopping
      behaviour at retail pharmacies. CONCLUSIONS: In the city and county of San
      Francisco, public support exists for prohibiting the sale of tobacco products in
      pharmacies.

PMID- 23172400
TI  - Patient-oriented rehabilitation in the management of chronic mechanical neck
      pain: a randomized controlled trial.
AB  - BACKGROUND: Management of chronic mechanical neck pain (CMNP) still represents a
      challenge. A patient-oriented (Pa-O) therapeutic approach could be considered as
      the one in which therapies are scheduled at the start of each therapeutic session
      according to the patient's current physical status, and differs from a
      prescription-oriented (Pr-O) therapeutic approach, in which therapies are
      prescribed at the first medical referral and are not adjusted at any time during
      the treatment period. AIM: To determine if a Pa-O approach may be more beneficial
      for CMNP patients when compared to a Pr-O one. DESIGN: Randomized controlled
      trial. POPULATION: 220 CMNP outpatients randomized to either Pa-O group (N.=114)
      or Pr-O group (N.=106). METHODS: Each group received 10 therapeutic sessions over
      3 weeks. Primary outcome measures were pain assessment, evaluated by Visual
      Analog-Scale (VAS), and disability level, evaluated by the Neck Pain and
      Disability Scale (NPDS-I). Secondary outcome measures included patients' response
      to treatment and treatment failures. Measurements were carried out at baseline
      (T0) and 1 month after treatment ended (T1). Data were analysed according to the
      intention-to-treat principle. RESULTS: Patients in both groups displayed at T1 a
      significant reduction in VAS and NPDS-I scores. The relative changes at T1 were
      greater in Pa-O group when compared with Pr-O group both for VAS (61.5% versus
      48.8%; P<0.005) and for NPDS-I scores (48.4% versus 36.8%; P<0.05). CONCLUSION: A
      Pa-O approach may be more beneficial in terms of pain and disability improvement
      in the short-term follow-up in suffers from CMNP. However, the occurrence of a
      performance-bias due to the increased level of attention from physicians to
      patients in Pa-O group, cannot be ruled-out. CLINICAL REHABILITATION IMPACT: A Pa
      O approach should be considered for CMNP also in an outpatient facility.

PMID- 23172402
TI  - Effects of treadmill training with partial body weight support and the
      proprioceptive neuromuscular facilitation method on hemiparetic gait: a
      randomized controlled study.
AB  - BACKGROUND: Gait disturbance is common after stroke; however, there is no
      consensus regarding the optimal therapeutic rehabilitation of hemiparetic gait.
      AIM: To compare the effects of the treadmill training with partial body-weight
      support (TPBWS) and Proprioceptive Neuromuscular Facilitation (PNF) method on
      gait of subjects with chronic stroke. DESIGN: Randomized clinical trial,
      comparing two experimental groups (comparative study). SETTING: Laboratory for
      Human Movement Analysis of UFRN. POPULATION: Twenty-three subjects, with a mean
      age of 56.7+/-8.0 years and a mean time since the onset of the stroke of 27.7+/
      20.3 months, able to walk with personal assistance or assistive devices. METHODS:
      Two experimental groups underwent gait training based on PNF method (N.=11) or
      using the TPBWS (N.=12), for twelve sessions. Evaluation of motor function (using
      the STREAM and motor FIM), and kinematic gait analysis were carried out before
      and after the interventions. RESULTS: Increases in the STREAM scores (F=49.189,
      P<0.001) and in motor FIM scores (F=7.093, P=0.016), as well as improvement in
      symmetry ratio-swing time of the paretic leg/swing time of non-paretic leg-
      (F=7.729, P=0.012), were observed for both groups. Speed, stride length and
      double-support time showed no change after training. Differences between groups
      were observed only for the maximum ankle dorsiflexion over the swing phase
      (F=6.046, P=0.024), which showed an increase for the PNF group. Other angular
      parameters remain unchanged. CONCLUSION: Improvement in motor function and in
      gait symmetry was observed for both groups, suggesting similarity of
      interventions. However, the sample size should be carefully considered in
      generalizing the results to other populations. CLINICAL REHABILITATION IMPACT:
      The results showed some equivalence between these two approaches with regard to
      motor recovery, functionality and temporal symmetry of hemiparetic gait,
      suggesting that the cost-effectiveness of each treatment may have a important
      role in this choice.

PMID- 23172403
TI  - Sony PlayStation EyeToy elicits higher levels of movement than the Nintendo Wii:
      implications for stroke rehabilitation.
AB  - BACKGROUND: Virtual reality (VR) is an emerging trend in stroke rehabilitation.
      VR gaming consoles in stroke intervention have been shown to increase motivation
      and enjoyment during exercise. The amount and intensity of movements elicited
      using these consoles are unknown. AIMS: The aims of this study were: (1) to
      quantify the amount and intensity of movement elicited from both hands of two
      groups of individuals ([chronic stroke and without a disability [healthy]); (2)
      to determine the effect of console (Wii/EyeToy) and group (stroke/healthy) on the
      amount and intensity of upper extremity movement; (3) to determine the effect of
      console (Wii/EyeToy) and group (stroke/healthy) on the usability and VR
      experience. DESIGN: A cross-sectional design was taken. SETTING: Outpatient
      rehabilitation setting and healthy participant's homes. POPULATION: Participants
      included ten adults with stroke and ten adults without a disability. METHODS:
      Participants experienced two games from each console. Amount and intensity of
      movement was measured using accelerometers on both wrists, while the virtual
      experience and usability was determined with questionnaires. RESULTS: No
      significant differences were found between the consoles usability and experience.
      EyeToy elicited significantly greater activity count than Wii among the healthy
      participants (P=0.028) and significantly greater movement intensity in both the
      stroke (P=0.005) and healthy (P=0.005) groups. CONCLUSION: Both consoles rated
      high for usability, enjoyment and satisfaction highlighting their suitability for
      a range of individuals in stroke rehabilitation. EyeToy provides increased
      movement and movement intensity. CLINICAL REHABILITATION IMPACT: Both consoles
      are suitable for use in stroke rehabilitation however this information can be
      helpful to clinicians while selecting a gaming console according to the type and
      intensity of movements that he/she aims to encourage during therapy.

PMID- 23172404
TI  - Motor strategies and bilateral transfer in sensorimotor learning of patients with
      subacute stroke and healthy subjects. A randomized controlled trial.
AB  - BACKGROUND: Bilateral transfer, i.e. the capacity to transfer from one to the
      other hand a learned motor skill, may help the recovery of upper limb functions
      after stroke. AIM: To investigate the motor strategies at the basis of
      sensorimotor learning involved in bilateral transfer. DESIGN: Randomized
      controlled trial. SETTING: Neurorehabilitation Hospital. POPULATION: Eighty right
      handed participants (65 +/- 13 years old): 40 patients with subacute stroke, 40
      control healthy subjects. METHODS: Subjects performed the 9 hole-peg-test twice
      in an order defined by random allocation: first with low and then with high
      skilled hand (LS-HS) or the reverse (HS-LS). Time spent to complete the test and
      filling sequence were recorded, together with maximum pinch force (assessed using
      a dynamometer), upper limb functioning (Motricity Index), spasticity (modified
      Ashworth Scale), limb dominance (Edinburgh Handeness Inventory). RESULTS: As
      expected, in patients, the performance was found related to the residual pinch
      force (P<0.001), upper limb motricity (P=0.006) and side of hemiparesis
      (P=0.016). The performances of all subjects improved more in HS-LS than in LS-HS
      subgroups (P=0.043). The strategy adopted in the first trial influenced the
      velocity in the second one (P=0.030). CONCLUSION: Bilateral transfer was observed
      from high to low skilled hand. Learning was not due to a mere sequence
      repetition, but on a strategy chosen on the basis of the previous performance.
      CLINICAL REHABILITATION IMPACT: The affected hand of patients with subacute
      stroke may benefit from sensorimotor learning occurred with the un-affected hand.

PMID- 23172405
TI  - Effect of supervision on ultrasonographic measurements. A blinded randomized
      cross-over study.
AB  - BACKGROUND: Musculoskeletal ultrasound is becoming an increasingly popular
      clinical tool in the hands of physiatrists. Herewith, although the role of direct
      supervision (by an expert) is universally recognized as the core element for
      appropriate ultrasound training, to our best notice, its impact on
      ultrasonographic measurements has not been studied quantitatively in the hitherto
      literature. AIM: To quantify the effect of supervision in the early period of
      musculoskeletal ultrasound training by using three different tissues (muscle
      cartilage-tendon) as models. DESIGN: A blinded randomized cross-over study.
      SETTING: Physical Medicine and Rehabilitation Department of a University
      Hospital. POPULATION: A total of 9 sonographers (8 novice and 1 expert) were
      involved whereby the novice sonographers were randomly divided into two groups;
      Group A (N.=4) and Group B (N.=4). METHODS: All sonographers performed three
      thickness measurements; medial head of the gastrocnemius muscle, patellar tendon
      and femoral cartilage on the left lower limb of the same subject. The expert
      supervised Group A in the first half of the study (9 days), and Group B in the
      second half (9 days). Throughout the study period, all the participants were
      blinded to the data. Relative effectiveness, expert effect, order effect,
      treatment-period effect were studied for cross-over variance analysis. RESULTS:
      For all the three sites, measurements under the supervision of the expert were
      significantly different than those without him -p values pertaining to relative
      effectiveness, expert effect were 0.014, 0.013 for femoral cartilage; <0.001,
      <0.001 for gastrocnemius and <0.001, <0.001 for patellar tendon, respectively).
      For gastrocnemius muscle measurements, studying with the expert in the second
      half of the study (vs in the first half) was better concerning the precision of
      the measurements (order effect P<0.001). CONCLUSION: Supervision during
      measurements of novice sonographers is crucial and their data should otherwise be
      interpreted attentively.

PMID- 23172406
TI  - Differential trajectory of functional recovery and determinants for first time
      stroke survivors by using a LCGA approach: a hospital based analysis over a 1
      year period.
AB  - BACKGROUND: Functional outcome and the risk factors for stroke survivors have
      explored in previous study. However, a comprehensive understanding of the
      patterns and critical risk factors of functional recovery is limited. AIM: To
      explore the trajectory groups and determinants of functional recovery for
      ischemic stroke patients during 1 year after stroke. DESIGN: Longitudinal study.
      SETTING: Inpatient. POPULATION: First-time stroke patients. METHOD: A total of
      367 first-time ischemic stroke patients from the Stroke Registry in the Chang
      Gung Hospital (SRICH) database were analyzed in this study. Study variables
      comprised demographic and disease characteristics, laboratory data, and
      functional outcome. The Latent Class Growth Analysis (LCGA) was used to identify
      various trajectory clusters and multinomial logistic regression was used to
      identify the predictors of functional recovery. RESULT: Five trajectory clusters
      of functional recovery were identified using the Barthel Index. Among five
      clusters of functional recovery, nearly 18% of first-ever ischemic stroke
      patients maintained functional dependence, whereas 82% of stroke patients
      demonstrated functional recovery; and the significant recovery time totaled three
      months after the stroke. Determinants for various trajectory clusters of
      functional recovery were body mass index and serum albumin level, especially a
      higher serum albumin concentration predicted a more favorable functional
      recovery. CONCLUSION: Our findings suggest that diverse functional recovery
      clusters persisted and serum albumin concentration at admission was a critical
      assessment factor. CLINICAL REHABILITATION: Such information could be useful for
      identifying the different rehabilitation needs of varying trajectory groups and
      for effectively improving functional ability among the ischemic stroke
      population.

PMID- 23172408
TI  - Validation of the ICF core set for neuromuscular diseases.
AB  - BACKGROUND: Understanding of the consequences of a neuromuscular disease (NMD)
      can improve when a valid sample of disease-specific categories based on the
      International Classification of Functioning, Disabilities, and Health (ICF) is
      available. OBJECTIVE: To examine the content validity of the initial ICF Core Set
      for neuromuscular diseases (NMDs). The initial ICF Core Set was developed for
      three chronic neurological diseases. DESIGN: A qualitative method. METHODS: To
      examine the content validity of the initial ICF Core Set for NMD, concepts in
      established disease-specific health-related Quality of Life Questionnaires
      (HRQOL) were compared with ICF categories. Next, the selected ICF categories were
      linked to the ICF categories in the initial ICF Core Set. RESULTS: All concepts
      in the HRQOL questionnaires, except one body function concept, were covered by
      the initial ICF Core Set. However, the NMD Core Set reflects a broader scope
      concerning health problems than the concepts in the HRQOL questionnaires do,
      especially concerning the "Participation" and "Environmental Factors" components.
      CONCLUSION: The NMD Core Set, as well as a measurement based on this Core Set,
      can contribute to a better understanding of the consequences of NMDs and can also
      serve as a basis for clinical practice, research, social security systems, and
      educational programs. CLINICAL REHABILITATION IMPACT: The newly developed NMD
      Core Set can be a basis for enhancing the development of rehabilitation
      interventions and improving overall health care for patients with a NMD.

PMID- 23172412
TI  - A conceptual model of root hair ideotypes for future agricultural environments:
      what combination of traits should be targeted to cope with limited P
      availability?
AB  - BACKGROUND: Phosphorus (P) often limits crop production and is frequently applied
      as fertilizer; however, supplies of quality rock phosphate for fertilizer
      production are diminishing. Plants have evolved many mechanisms to increase their
      P acquisition, and an understanding of these traits could result in improved long
      term sustainability of agriculture. This Viewpoint focuses on the potential
      benefits of root hairs to sustainable production. SCOPE: First the various root
      related traits that could be deployed to improve agricultural sustainability are
      catalogued, and their potential costs and benefits to the plant are discussed. A
      novel mathematical model describing the effects of length, density and longevity
      of root hairs on P acquisition is developed, and the relative benefits of these
      three root-hair traits to plant P nutrition are calculated. Insights from this
      model are combined with experimental data to assess the relative benefits of a
      range of root hair ideotypes for sustainability of agriculture. CONCLUSIONS: A
      cost-benefit analysis of root traits suggests that root hairs have the greatest
      potential for P acquisition relative to their cost of production. The novel
      modelling of root hair development indicates that the greatest gains in P-uptake
      efficiency are likely to be made through increased length and longevity of root
      hairs rather than by increasing their density. Synthesizing this information with
      that from published experiments we formulate six potential ideotypes to improve
      crop P acquisition. These combine appropriate root hair phenotypes with
      architectural, anatomical and biochemical traits, such that more root-hair zones
      are produced in surface soils, where P resources are found, on roots which are
      metabolically cheap to construct and maintain, and that release more P-mobilizing
      exudates. These ideotypes could be used to inform breeding programmes to enhance
      agricultural sustainability.

PMID- 23172413
TI  - Racemose inflorescences of monocots: structural and morphogenetic interaction at
      the flower/inflorescence level.
AB  - BACKGROUND: Understanding and modelling early events of floral meristem
      patterning and floral development requires consideration of positional
      information regarding the organs surrounding the floral meristem, such as the
      flower-subtending bracts (FSBs) and floral prophylls (bracteoles). In common with
      models of regulation of floral patterning, the simplest models of phyllotaxy
      consider only unbranched uniaxial systems. Racemose inflorescences and thyrses
      offer a useful model system for investigating morphogenetic interactions between
      organs belonging to different axes. SCOPE: This review considers (1) racemose
      inflorescences of early-divergent and lilioid monocots and their possible
      relationship with other inflorescence types, (2) hypotheses on the morphogenetic
      significance of phyllomes surrounding developing flowers, (3) patterns of FSB
      reduction and (4) vascular patterns in the primary inflorescence axis and lateral
      pedicels. CONCLUSIONS: Racemose (partial) inflorescences represent the
      plesiomorphic condition in monocots. The presence or absence of a terminal flower
      or flower-like structure is labile among early-divergent monocots. In some
      Alismatales, a few-flowered racemose inflorescence can be entirely transformed
      into a terminal 'flower'. The presence or absence and position of additional
      phyllomes on the lateral pedicels represent important taxonomic markers and key
      features in regulation of flower patterning. Racemose inflorescences with a
      single floral prophyll are closely related to thyrses. Floral patterning is
      either unidirectional or simultaneous in species that lack a floral prophyll or
      possess a single adaxial floral prophyll and usually spiral in the outer perianth
      whorl in species with a transversely oriented floral prophyll. Inhibitory fields
      of surrounding phyllomes are relevant but insufficient to explain these patterns;
      other important factors are meristem space economy and/or the inhibitory activity
      of the primary inflorescence axis. Two patterns of FSB reduction exist in basal
      monocots: (1) complete FSB suppression (cryptic flower-subtending bract) and (2)
      formation of a 'hybrid' organ by overlap of the developmental programmes of the
      FSB and the first abaxial organ formed on the floral pedicel. FSB reduction
      affects patterns of interaction between the conductive systems of the flower and
      the primary inflorescence axis.

PMID- 23172415
TI  - The anomeric effect: the dominance of exchange effects in closed-shell systems.
AB  - The origin of the anomeric effect has remained an open question. After Mo
      demonstrated that hyperconjugation is not responsible for the anomeric effect [Y.
      Mo, Nature Chem., 2010, 2, 666.], electrostatic interactions and Pauli repulsions
      have been at the center of this debate. In this work, the total energies of the
      most stable rotamers of the equatorial and axial anomers of fluoro, hydroxyl,
      cyano and amino groups in cyclohexane and 2-substituted tetrahydropyran rings are
      decomposed into their fundamental kinetic, electrostatic and exchange components.
      In this partitioning scheme, the differences in the total energies among the most
      stable rotamers of each anomer correlate very well with the differences in the
      exchange components, revealing that the anomeric effect has no electrostatic
      origin. Indeed, the anomeric effect is dominated by the exchange energy. This
      proposal for the origin of the anomeric effect brings new insights that, once
      incorporated, may improve qualitative chemical models. Implications of this new
      proposal for the origin of the anomeric effect on geometric parameters and
      solvation are also discussed.

PMID- 23172414
TI  - High-throughput root phenotyping screens identify genetic loci associated with
      root architectural traits in Brassica napus under contrasting phosphate
      availabilities.
AB  - BACKGROUND AND AIMS: Phosphate (Pi) deficiency in soils is a major limiting
      factor for crop growth worldwide. Plant growth under low Pi conditions correlates
      with root architectural traits and it may therefore be possible to select these
      traits for crop improvement. The aim of this study was to characterize root
      architectural traits, and to test quantitative trait loci (QTL) associated with
      these traits, under low Pi (LP) and high Pi (HP) availability in Brassica napus.
      METHODS: Root architectural traits were characterized in seedlings of a double
      haploid (DH) mapping population (n = 190) of B. napus ['Tapidor' * 'Ningyou 7'
      (TNDH)] using high-throughput phenotyping methods. Primary root length (PRL),
      lateral root length (LRL), lateral root number (LRN), lateral root density (LRD)
      and biomass traits were measured 12 d post-germination in agar at LP and HP. KEY
      RESULTS: In general, root and biomass traits were highly correlated under LP and
      HP conditions. 'Ningyou 7' had greater LRL, LRN and LRD than 'Tapidor', at both
      LP and HP availability, but smaller PRL. A cluster of highly significant QTL for
      LRN, LRD and biomass traits at LP availability were identified on chromosome A03;
      QTL for PRL were identified on chromosomes A07 and C06. CONCLUSIONS: High
      throughput phenotyping of Brassica can be used to identify root architectural
      traits which correlate with shoot biomass. It is feasible that these traits could
      be used in crop improvement strategies. The identification of QTL linked to root
      traits under LP and HP conditions provides further insights on the genetic basis
      of plant tolerance to P deficiency, and these QTL warrant further dissection.

PMID- 23172416
TI  - Euthanasia: India's position in the global scenario.
AB  - BACKGROUND: Euthanasia requests have increased as the number of debilitated
      patients rises in both developed and developing countries such as India due to
      medical, psychosocial-emotional, socioenvironmental, and existential issues amid
      fears of potential misuse. WORLD'S POSITION: Albania, Colombia, the Netherlands,
      and Switzerland permit euthanasia conditionally. Australia's legalization of
      euthanasia has been withdrawn. The United States permits withdrawal of life
      support. Mexico and Norway permit active euthanasia. INDIA'S POSITION: Following
      the Aruna Shanbaug case the Supreme Court granted legal sanction to passive, but
      not active, euthanasia that is valid till the Parliament legislates on
      euthanasia. HANDLING EUTHANASIA REQUESTS: Acknowledging the complexity of the
      problem; individualizing the palliative approach; and accepting the 'There is no
      alternative' or 'There is no answer' (TINA) factor.

PMID- 23172417
TI  - Adult malignant brain tumors: palliative medicine issues (part I).

PMID- 23172418
TI  - Inadvertent ophthalmic administration of atropine drops in a hospice patient.
AB  - This case report describes a patient who had atropine ophthalmic drops prescribed
      and dispensed by hospice to be administered sublingually as needed for control of
      secretions at the end of life. However, even as she stabilized and discharged
      from hospice, these remained on her medication list. At a subsequent
      hospitalization, this order was misinterpreted and the drops were ordered to be
      administered in both the eyes 3 times a day while in the hospital and were
      included in her discharge medication list. The patient experienced severe
      blurring of vision until the error was corrected. This case highlights the
      potential risks of the common practice in hospice of using alternate routes of
      administration for medications designed for another purpose. 

PMID- 23172419
TI  - Effect of gestational age on first trimester maternal serum prenatal screening
      correction factors for ethnicity and IVF conception.
AB  - OBJECTIVE: The aim of this study is to investigate gestational age effects of
      maternal ethnicity and in vitro fertilization (IVF) pregnancy correction factors
      of first trimester trisomy 21 screening markers pregnancy associated plasma
      protein A (PAPP-A) and free-beta human chorionic gonadotropin (free hCGbeta) in a
      large dataset. METHODS: Data from 205,341 normal singleton pregnancies were
      retrieved, and PAPP-A and free hCGbeta concentrations were converted to multiples
      of the medians (MoMs) uncorrected for either maternal ethnicity or IVF pregnancy.
      Log(10) transformed MoMs were plotted against gestational age in each group to
      examine gestational age effects RESULTS: Significant gestational age effects were
      found for correction factors for PAPP-A in Afro-Caribbean, South Asian and East
      Asian, and for free hCGbeta in Afro-Caribbean and IVF pregnancy. CONCLUSIONS:
      Current single correction factors for PAPP-A and free hCGbeta based on maternal
      ethnicity and IVF pregnancy are inappropriate, and future screening algorithms
      need to take into account the change in effect of these factors with gestational
      age.

PMID- 23172420
TI  - Development of octadecyl-functionalized-nanotubular TiO2/Ti wire solid-phase
      microextraction fiber.
AB  - An octadecyl-functionalized solid-phase microextraction (SPME) fiber was prepared
      by sol-gel technology with an anodized Ti wire as the substrate and
      dimethyloctadecyl[3-(trimethoxysilyl)propyl]ammonium chloride (C(18)-TMS) and
      tetraethoxysilane (TEOS) as sol-gel precursors. The anodized Ti wire has high
      mechanical strength and has numerous titanol groups on its surface for sol-gel
      reactions, consequently offering better performances than the commercial fragile
      fused silica substrate. The C(18)-TMS/TEOS sol-gel coated fiber has good thermal
      stability and stability against organic solvents. There is no loss in the
      performance after 100 cycles of exposure to acetonitrile and high temperature
      (300  degrees C) in turn. The developed fiber with a very thin (ca. 2 MUm)
      coating thickness exhibits comparable or even superior extraction capability
      relative to the commercial 100 MUm polydimethylsiloxane (PDMS) fiber. Under
      optimized conditions, the detection limits for the polycyclic aromatic
      hydrocarbons are in the range of 0.003 to 0.025 MUg L(-1) with a linear range
      from 0.01 to 20 MUg L(-1). The proposed method was successfully applied in the
      analysis of environmental water samples with the recoveries ranging from 85.3 to
      101.8%.

PMID- 23172421
TI  - Urokinase receptor mediates doxorubicin-induced vascular smooth muscle cell
      senescence via proteasomal degradation of TRF2.
AB  - The anthracycline doxorubicin is a widely used effective anti-cancer drug.
      However, its application and dosage are severely limited due to its
      cardiotoxicity. The exact mechanisms of doxorubicin-induced cardiotoxic side
      effects remain poorly understood. Even less is known about the impact of
      doxorubicin treatment on vascular damage. We found that low doses of doxorubicin
      induced a senescent response in human primary vascular smooth muscle cells
      (VSMC). We observed that expression of urokinase receptor (uPAR) was upregulated
      in response to doxorubicin. Furthermore, the level of uPAR expression played a
      decisive role in developing doxorubicin-induced senescence. uPAR silencing in
      human VSMC by means of RNA interference as well as uPAR knockout in mouse VSMC
      resulted in abrogation of doxorubicin-induced cellular senescence. On the
      contrary, uPAR overexpression promoted VSMC senescence. We further found that
      proteasomal degradation of telomeric repeat binding factor 2 (TRF2) mediates
      doxorubicin-induced VSMC senescence. Our results demonstrate that uPAR controls
      the ubiquitin-proteasome system in VSMC and regulates doxorubicin-induced TRF2
      ubiquitination and proteasomal degradation via this mechanism. Therefore, VSMC
      senescence induced by low doses of doxorubicin may contribute to vascular damage
      upon doxorubicin treatment. uPAR-mediated TRF2 ubiquitination and proteasomal
      degradation are further identified as a molecular mechanism underlying this
      process.

PMID- 23172422
TI  - Automatic particle detection and sorting in an electrokinetic microfluidic chip.
AB  - This paper reports a lab-on-a-chip device that can automatically detect and sort
      particles based on their size differences with a high resolution. The PDMS-glass
      microfluidic chip is made by soft-lithography technique. A differential resistive
      pulse sensor is employed to electrically detect the sizes of the particles in EOF
      generated by applying DC voltages across channels. The detected resistive pulse
      sensor signals, whose amplitudes are proportional to particles' sizes, will
      automatically trigger the sorting process that is controlled by applying a
      voltage pulse (36 V) whenever a target particle is detected. This method was
      applied to automatically detect and sort polystyrene particles and microalgae in
      aqueous solutions. Sorting 5 MUm polymer particle from a mixture of 4- and 5-MUm
      polystyrene particles in aqueous solution, i.e. 1 MUm sorting resolution, was
      demonstrated. The device described in this paper is simple, automatic, and label
      free with high sorting resolution. It has wide applications in sample
      pretreatment and target particles detection.

PMID- 23172424
TI  - Craniofacial and pediatric plastic surgery: the future is definitely on the
      forward mode.

PMID- 23172425
TI  - Characterization of midface fractures incurred in recent wars.
AB  - BACKGROUND: Facial injuries sustained by US military personnel during the wars in
      Iraq and Afghanistan have increased compared with past conflicts.
      Characterization of midface fractures (orbits, maxilla, zygoma, and nasal bones)
      sustained on the battlefield is needed to improve our understanding of these
      injuries, to optimize treatment, and to potentially direct strategic development
      of protective equipment in the future. METHODS: The military's Joint Theater
      Trauma Registry was queried for midface fractures from 2001 to 2011 using
      International Classification of Diseases, Ninth Revision diagnosis codes.
      Stratification was then performed, and individual treatment records from Brooke
      Army Medical Center were reviewed. Analysis of the fracture pattern, treatment,
      and complications was performed. RESULTS: One thousand seven hundred sixty
      individuals with midface fractures were identified. Those fractures sustained in
      battle were characterized by a predominance of open fractures, blast etiology,
      and associated injuries. Detailed record reviews of the patients treated at our
      institution revealed 45% of all midface fractures as operative. Thirty-one
      percent of these were treated at levels III and IV facilities outside the
      continental United States before arrival at our institution. Patients with
      midface fractures underwent multiple operations. There was a 30% rate of
      complication among operative fractures characterized by malalignment, implant
      exposure, and infection. Midface battle injuries also had a high incidence of
      orbital fractures and severe globe injuries. CONCLUSIONS: Midface fractures
      sustained in the battlefield have a high complication rate, likely as a result of
      the blast mechanism of injury with associated open fractures, multiple fractures,
      and associated injuries. These cases present unique challenges, often requiring
      both soft tissue and skeletal reconstruction.

PMID- 23172426
TI  - Perforating frontal branch of the superficial temporal artery as related to
      subcutaneous forehead lift.
AB  - The aim of this study was to elucidate the precise anatomy of the perforating
      branch of the superficial temporal artery in relation to subcutaneous forehead
      lift (SFL).Ten hemifaces of 6 fresh adult Korean cadavers were used in this
      study. In 4 hemifaces, following injection of red latex, dissection was
      performed. In 2 hemifaces, following injection of methylene blue solution into
      the perforator, the area of discoloration was observed. An artery perforating the
      frontalis muscle into skin of the forehead was identified in 18 foreheads of 9
      patients who underwent SFL. Measurements were taken of the external diameter and
      the location of the perforator.Perforating branches originating from the frontal
      branch of the superficial temporal artery, perforating the frontalis muscle into
      skin of the forehead, were observed in all 10 of the dissected hemifaces.
      Thereafter, it was referred to as the perforating frontal artery (PFA). Skin of
      the ipsilateral mid-forehead was discolored by methylene blue solution. Most of
      the PFA (83%) was included in a circle having a radius of 8.9 mm. The center of
      the circle was located 40.5 mm from the midline on the x axis and 53.6 mm from
      the supraorbital rim (on the y axis). The center of the circle was located at
      89.8% of the length of the midline to the lateral canthus (x axis) and 79.1% of
      the length of the supraorbital rim to the hairline (y axis).Plastic surgeons can
      use the PFA in order to achieve sufficient circulation of the skin flap. When
      surgeons are required to sacrifice the PFA in order to achieve flap mobilization,
      they can safely cauterize the PFA after isolation without causing accidental burn
      injury to the skin flap. In addition, the PFA might be useful in creation of
      local or distant flaps for reconstruction of the forehead or scalp.

PMID- 23172427
TI  - Location of the vascular arcade superficial and deep to the Muller muscle related
      to blepharoptosis surgery.
AB  - The aim of this study is to elucidate the location of the vascular arcades of the
      Muller muscle as it is related to blepharoptosis surgery. A total of 28 eyelids
      of 14 patients were observed. In 4 hemifaces of 2 fresh Korean adult cadavers,
      injection of red latex and dissection were performed via a cutaneous and
      conjunctival approach. Measurements were performed for determination of distances
      from the upper margin of the tarsal plate to the visible vascular arcades. Two
      parallel vascular arcades were observed through the conjunctiva. The distance
      from the upper margin of the tarsal plate to the visible vascular arcade was 6.86
      +/- 0.53 mm (lower arcade) and 11.71 +/- 0.73 mm (upper arcade), respectively.
      Using the skin approach, an upper vascular arcade was observed between the
      levator aponeurosis and the Muller muscle. Using the conjunctival approach, a
      lower vascular arcade was observed between the conjunctival epithelium and the
      Muller muscle. We hope that these two vascular arcades can be regarded as
      landmarks for placating the Muller muscle in blepharoptosis surgery.

PMID- 23172428
TI  - Internal carotid artery in endoscopic endonasal transsphenoidal surgery.
AB  - The transsphenoidal approach to the pituitary is widely used in pituitary
      surgery. Even though there are some landmarks for internal carotid artery (ICA)
      on the wall of the sphenoid sinus, it is not rare to get the artery injured
      during surgery. We found that the most important landmark, carotid prominence,
      matched with ICA in merely 37.5% of subjects. In order to find a simple method to
      locate the artery, we made an anatomical measurement of the ICA and placed the
      results in a 3-dimensional coordinate system. The sphenoid sinus opening is both
      the center of the endoscope entry in the anterior sinus wall and the origin of
      the coordinate system containing 3 orthogonal axes: x, y, and z. The x axis
      follows the body of the endoscope(out of the sphenoid sinus) parallel to the
      sagittal plane while z is perpendicular to the sagittal plane. Most of the
      measurements were obtained in the initial operative plane, which is perpendicular
      to the sagittal plane and contains the sinus opening and the midpoint of the
      pituitary fossa. We calculated the coordinates of the midpoint of the pituitary
      fossa and 4 ICA-related points. The depth of an ICA and the distance between 2
      ICAs are also helpful in locating ICA. According to our operation method, all the
      projective points of the medial edge of ICA on the posterior wall of the sphenoid
      sinus are lateral to the sphenoid sinus opening, and operating within 0-25
      degrees medial to the endoscope body is believed to be safe from ICA injury.

PMID- 23172429
TI  - Lateral orbital rim; open or closed in mammals.
AB  - We tried to determine the relationship between the presence of the lateral
      orbital rim and shape of the skull in certain mammals. From the literature, 15
      mammals with the orbit closed at the back by a bony bar (closed group) and 18
      mammals with the orbit closed at the back without a bony bar (open group) were
      selected. Calculation of interorbital-zygomatic breadth ratio (IZR, interorbital
      breadth/zygomatic breadth) and nasal-skull ratio (NSR, length of nasals/greatest
      length of skull) was performed.IZR of the closed group (0.73 +/- 0.27) was
      significantly greater than that of the open group (0.35 +/- 0.63, P = 0.000). NSR
      of the closed group (0.32 +/- 0.97) was significantly lower than that of the open
      group (0.41 +/- 0.67, P = 0.023).The open group (primarily carnivores) showed a
      lower interorbital-zygomatic breadth ratio, and here both orbits were located in
      close proximity. Although this bony structural arrangement is favorable for
      stereoscopic vision, the total field of view particularly lateral vision becomes
      limited. It is our view that the opened lateral orbital rim compensates for the
      limited lateral vision.

PMID- 23172430
TI  - Bony tubercle at external occipital protuberance and prominent ridges.
AB  - During the examination of skulls in the osteology laboratory of the Department of
      Anatomy, CSM Medical University, Lucknow, UP, India, a skull was detected having
      exostosis projecting from the external occipital protuberance along with
      prominent superior nuchal lines appearing as ridges. Measurements of the tubercle
      were taken by vernier calipers, and possible causes and clinical implications
      were analyzed.The length of this tubercle was 8 mm; width was 6 mm and thickness
      1.5 mm. The superior nuchal lines appeared as prominent ridges. The height of the
      ridges was 5 mm on both sides; the thickness was 10 mm and 8 mm, respectively, on
      both the right and left sides. The length of the ridges was 4.8 cm on the right
      side and 4.4 cm on the left side.The tubercle may cause occipital headache in
      general but especially in tree climbers and basketball/volleyball players during
      vertical biomechanical movements of the neck. The knowledge of this tubercle is
      of paramount importance to anatomists, neurosurgeons, sports physicians,
      radiologists, forensic experts, and anthropologists.

PMID- 23172431
TI  - Do upper and lower orbital fat have a connection?
AB  - This study, using cadavers, was conducted to determine whether there is a true
      connection between upper and lower orbital fat. A total of 39 orbits of 20 fresh
      Korean adult cadavers were used. Colored gelatin was injected into the upper or
      lower peripheral fat (preaponeurotic fat) of each orbit. One week after
      injection, dissection was continued and connection of the upper and lower orbital
      fat was examined. No migration of gelatin injected into the upper or to the
      central fat (intermuscular cone fat) was observed. However, migration of gelatin
      injected into the upper or lower preaponeurotic fat into the entire episcleral
      space through the adipose orifice (AO) was observed. The 3 sides of the upper AO
      consisted of the superior oblique muscle before the trochlea, superior oblique
      tendon after the trochlea, and sclera. The 3 sides of the lower AO consisted of
      the inferior oblique muscle, lateral rectus muscle, and fascia between the
      inferior rectus muscle and lateral rectus muscle. The upper AO was located at the
      medial one third of the orbital width and superior one fifth of the orbital
      height. The lower AO was located at the lateral one third of the orbital width
      and inferior one fifth of the orbital height. The shape of the upper AO was a
      triangle with a base of 4.3 +/- 2.0 mm and a height of 2.3 +/- 1.2 mm. The shape
      of the lower AO was a triangle with a base of 4.5 +/- 1.8 mm and a height of 2.7
      +/- 1.1 mm. We think that surgical obliteration of the AO might prevent migration
      of preaponeurotic fats. Prevention of migration of preaponeurotic fats will aid
      in avoidance of baggy lower eyelid or deepening of the supratarsal fold.

PMID- 23172432
TI  - Antiadhesive effect of mixed solution of sodium hyaluronate and sodium
      carboxymethylcellulose after blow-out fracture repair.
AB  - Treatment of blow-out fractures is aimed at the prevention of permanent diplopia
      and cosmetically unacceptable enophthalmos. Porous polyethylene sheets are one of
      the most common alloplastic implants for blow-out fracture repair. Because
      adhesion between the porous polyethylene and the orbital soft tissue can result
      in restrictions of ocular motility, prevention of postoperative adhesion is
      important in the reconstruction of blow-out fractures. The purpose of this study
      was to find out the effect of the mixed solution of sodium hyaluronate and sodium
      carboxymethylcellulose (HACMC) on postoperative adhesion in blow-out fracture
      repair in an animal model.Twenty-four New Zealand white rabbits were used. An 8
      mm defect was made in the maxillary sinuses including the bone and mucosa. A 10
      mm porous polyethylene sheet (Medpor; Porex Surgical Inc., Newnan, GA) was
      inserted in to the defect. The rabbits were divided into a control group and a
      HACMC group. In the HACMC group, HACMC solution was instilled onto the surface of
      the implant and then the implant was inserted. The implants were harvested at 1,
      2, 4, and 8 weeks after surgery (3 implants each period). Hematoxylin and eosin,
      Masson trichrome, and CD31 (platelet endothelial cell adhesion molecule-1) stains
      were performed for evaluation of inflammation, fibrosis, and
      vascularization.Inflammation appeared less severe in the HACMC group, but the
      difference between the 2 groups was not statistically significant. The degree of
      fibrosis was more severe in the control group. There were significant differences
      in the degree of fibrosis between the 2 groups 4 and 8 weeks after surgery (P =
      0.046). The amount of vascularization was similar in both groups.The HACMC
      solution seemed to be effective for reducing postoperative adhesion in
      reconstruction of blow-out fractures in a rabbit model. Our results suggest that
      the application of HACMC solution could be an effective adjunct for the repair of
      trap-door fractures or revision of blow-out fractures.

PMID- 23172433
TI  - Rotating distraction osteogenesis to enlarge the skull space.
AB  - BACKGROUND: Distraction osteogenesis has been used to treat diminished skull
      space caused by craniosynostosis. Our report investigated the relationship
      between space volume change by computer technology and the intracranial pressure
      change. Cerebrospinal fluid (CSF) regular test and CSF biochemistry test were
      also performed to ensure the safety of distraction process. METHODS: Seven
      minipigs, weighing 15 to 20 kilograms, were chosen; 4 * 3 cm bone flap was lifted
      in the left parietal bone. The dura was carefully protected. The distractor and
      assisted apparatus were implanted. Distraction was started with 10-day latency, 1
      mm/d distraction rates for 10 days. Twelve weeks after distraction, the
      distraction device and the assist apparatus were removed. All pigs underwent 3
      dimensional computerized scans of the craniofacial skeleton, CSF pressure
      measurement, CSF regular test, and CSF biochemistry test before operation, after
      7 days' operation, immediately after distraction was finished, 4 weeks after
      distraction, 8 weeks after distraction, and 12 weeks after distraction. The 3
      dimensional datum was collected, and volume change of skull was measured by 3
      dimensional medicine surface rendering software. RESULTS: All pigs tolerated the
      procedure. The mean volume 12 weeks after distraction was 87.93 +/- 3.11 cm,
      which was also significantly higher than 79.46 +/- 3.15 cm that of before
      operation (P < 0.001). The CSF pressure becomes maxim after 7 days' operation.
      The CSF pressure went down immediately after distraction was finished. Then, the
      CSF pressure kept stable but lower than the CSF pressure before the operation
      except 1 pig whose CSF pressure after operation was higher than the CSF pressure
      before the operation. Cerebrospinal fluid regular test and CSF biochemistry test
      show stable results, and the WBC does not rise during the whole process.
      CONCLUSIONS: The distraction osteogenesis is an efficient and safe method to
      enlarge the intracranial volume. The assisted apparatus of distraction is useful
      for rotating distraction. Three-dimensional DICOM datum and 3-dimensional
      medicine surface rendering are efficient for measurement of skull volume.

PMID- 23172434
TI  - Three-dimensional finite element analysis of stress distribution on different
      bony ridges with different lengths of morse taper implants and prosthesis
      dimensions.
AB  - This finite element analysis (FEA) compared stress distribution on different bony
      ridges rehabilitated with different lengths of morse taper implants, varying
      dimensions of metal-ceramic crowns to maintain the occlusal alignment. Three
      dimensional FE models were designed representing a posterior left side segment of
      the mandible: group control, 3 implants of 11 mm length; group 1, implants of 13
      mm, 11 mm and 5 mm length; group 2, 1 implant of 11 mm and 2 implants of 5 mm
      length; and group 3, 3 implants of 5 mm length. The abutments heights were 3.5 mm
      for 13- and 11-mm implants (regular), and 0.8 mm for 5-mm implants (short).
      Evaluation was performed on Ansys software, oblique loads of 365N for molars and
      200N for premolars. There was 50% higher stress on cortical bone for the short
      implants than regular implants. There was 80% higher stress on trabecular bone
      for the short implants than regular implants. There was higher stress
      concentration on the bone region of the short implants neck. However, these
      implants were capable of dissipating the stress to the bones, given the applied
      loads, but achieving near the threshold between elastic and plastic deformation
      to the trabecular bone. Distal implants and/or with biggest occlusal table
      generated greatest stress regions on the surrounding bone. It was concluded that
      patients requiring short implants associated with increased proportions implant
      prostheses need careful evaluation and occlusal adjustment, as a possible
      overload in these short implants, and even in regular ones, can generate stress
      beyond the physiological threshold of the surrounding bone, compromising the
      whole system.

PMID- 23172435
TI  - Morphological study of transpterional-insula approach using volume rendering.
AB  - This study describes the measurements of inferior circular insular sulcus (ICIS)
      and the shortest distance from ICIS to the temporal horn and determines the
      position of the incision, which does less harm to the temporal stem in the
      transpterional-insula approach using volume-rendering technique. Results of the
      research showed that one-third point over the anterior side of ICIS may be the
      ideal penetration point during operation. And there is no difference between 2
      hemispheres (P < 0.05). The comparison with the results of ICIS from other
      Chinese researches demonstrated that volume rendering is a reliable method in
      insular research that enables mass measurements.

PMID- 23172436
TI  - Facial dermis grafts after removal of basal cell carcinomas.
AB  - Selecting a proper reconstruction method is the key to success in skin cancer
      management, especially for lesions involving the face. Using a skin graft is
      usually straightforward when covering a skin defect; however, major concerns in
      skin grafting include a poor color match in the recipient-site and donor-site
      morbidity. To overcome these limitations, the authors have developed a dermis
      graft, which utilizes a de-epithelialized split-thickness skin graft method. The
      purpose of this retrospective study was to report reliability of dermis grafts
      after removal of basal cell carcinomas (BCCs) on the face by presenting our
      clinical experience with them. This study included 38 patients who were treated
      for facial defects created by resection of BCCs. The locations of the defects
      were as follows: nose (n = 17), orbital area (n = 14), cheek (n = 4), temple area
      (n = 2), and forehead (n = 1). The defects ranged in size from 3.3 to 6.5 cm.
      Functional and cosmetic outcomes, postoperative complications, and patient
      satisfaction were assessed. The patients were followed up for 12 to 36 months.
      The entire dermis graft re-epithelialized after grafting within 17 to 27 days.
      Most of the patients had satisfactory results in both functional and cosmetic
      matters with high-quality skin characteristics. There were no significant
      complications and no recurrences were observed during the follow-up period.
      Patient satisfaction with the dermis graft was also excellent. The dermis graft
      may be used reliably for covering defects after removal of BCCs on the face.

PMID- 23172437
TI  - Correction of facial asymmetry resulting from hemimandibular hyperplasia: 
      surgical steps to the esthetic result.
AB  - Hemimandibular hyperplasia is a facial deformity in which there is an increase in
      the condyle, neck of the condyle or ramus, and an occlusal cant. Different
      surgical treatments are proposed in the literature, from simple low or high
      condylectomy to more complex procedures combining osteotomies in different sites
      of the mandible. Surgical procedure is defined by the scintigraphic diagnosis of
      activity or inactivity in the center of condylar growth. The case report
      describes a 35-year-old female patient with hemimandibular hyperplasia on the
      left side with inactivity of condylar growth, successfully treated with bilateral
      sagittal split ramus osteotomy associated with a basilar osteotomy in form of "L"
      on the affected side. The surgical technique was easily executed, with an
      improvement in function, aesthetics, and patient satisfaction. Correction of
      facial asymmetry caused by excessive growth of the mandible using this basilar
      osteotomy in the form of "L" combined with bilateral sagittal split ramus
      osteotomy proved to be a relatively simple technique of easy execution with a low
      risk of nerve damage.

PMID- 23172438
TI  - Superficial skin sensitivity impairment and skeletal stability after sagittal
      split ramus osteotomy.
AB  - Adjustable osteosynthesis miniplates are used to facilitate positioning of the
      mandible after bilateral sagittal split osteotomy (BSSO) to avoid skeletal
      relapse and occlusal discrepancies. The short Obwegeser BSSO reduces neurosensory
      disturbances. Adjustable osteosynthesis plates suited for the Obwegeser BSSO are
      not commercially available. This study tested adjustable miniplates for the short
      Obwegeser BSSO in advancement of the mandible and correction of facial asymmetry,
      assessing (1) sensitivity impairment of the lower lip and (2) skeletal
      stability.A prototype of L-shaped, 6-hole, 2.0-mm miniplate with 2 sliding holes
      was used. Five patients with facial asymmetry (group 1) and 10 patients with
      mandibular hypoplasia (group 2) were operated on. Sensitivity of the lower lip
      was quantified using the pain and thermal sensitivity test before the surgery
      (T0), 1 week after the surgery (T1), and 12 months after the surgery (T2). The
      length of the ascending ramus (group 1) and the corpus (group 2) was determined
      at T1 and T2 using cone beam computed tomographic scans and lateral skull
      radiographs, respectively.After the surgery, occlusion was adequate. There was no
      need for revisional surgery. At T2, no patient showed a pathologically reduced
      sensitivity of the lower lip. The length of the ascending ramus in group 1 and
      the length of the corpus in group 2 did not have statistically significant
      changes between T1 and T2.The current study revealed that the adjustable
      osteosynthesis plates especially designed for the short Obwegeser BSSO can be
      safely used for the advancement of the mandible and the correction of facial
      asymmetry, with a minimum risk for neurosensory disturbance and a high skeletal
      stability.

PMID- 23172439
TI  - Elements of implant-supported rehabilitation planning in patients with bruxism.
AB  - The rehabilitation of partial or completely edentulous patients with implant
      supported prostheses has been widely used, achieving high success rates. However,
      many studies consider the presence of bruxism as a contraindication for this
      treatment modality. The purpose of this study was to revise the literature and
      identify risk factors in implant-supported rehabilitation planning in subjects
      with bruxism. Available literature was searched through Medline, with no time
      limit, including only studies in English. Topics discussed were etiology of
      bruxism and its implications on dental implants, biomechanical considerations
      regarding the overload on dental implants, and methods to prevent the occurrence
      of overloads in implant-supported prostheses. The rehabilitation of bruxers using
      implant-supported prostheses, using implants with adequate length and diameter,
      as well as proper positioning seems to be a reliable treatment, with reduced
      risks of failure. Bruxism control through the use of a nightguard by rigid
      occlusal stabilization appliance relieved in the region of implants is highly
      indicated. Although it is clear that implant-supported rehabilitation of patients
      with bruxism requires adequate planning and follow-up, well-designed randomized
      controlled trials are needed to provide reliable evidence on the long-term
      success of this treatment modality.

PMID- 23172440
TI  - Chondroma located in cerebral parenchyma without meningeal attachment.
AB  - Intracranial chondromas are rare benign tumors, which usually originate from
      skull base synchondrosis. In rarer cases, intracranial chondromas originate from
      the cerebral parenchyma without meningeal attachment, which is defined as
      intracerebral chondroma. In this paper, an 18-year-old male patient with
      intracerebral chondroma is presented. There are only 5 cases of intracerebral
      chondromas without meningeal attachment published in the literature. According to
      the clinical data, the intracerebral chondromas are hard hyaline cartilage,
      irregular lobulated grayish-white mass macroscopically and consist of mature
      hyaline chondrocyte microscopically. Total removal is the best treatment method
      for intracerebral chondroma.

PMID- 23172441
TI  - Late metastasis of an intracranial meningioma to the hard palate.
AB  - Meningiomas are benign neoplasms that arise from cellular elements of the
      meninges. Although meningiomas are usually considered as benign tumors, they have
      a potential to become aggressive and to metastasize to the extracranial
      structures. Distant metastasis most commonly occurs in lung, liver, and long
      bones. We present an extremely rare case of a delayed metastasis of a recurrent
      intracranial meningioma to the hard palate 19 years after the initial diagnosis.
      The patient underwent surgical excision without any complication and follow-up
      showed no recurrence.

PMID- 23172442
TI  - Alar rim neurothekeoma in a child.
AB  - OBJECTIVE: We report on the case of an 11-year-old girl with atypical
      neurothekeoma of the left lateral alar rim that was excised and ultimately closed
      primarily after an unsuccessful attempt at reconstruction with a full-thickness
      auricular composite graft. METHODS: In this case report, we present a description
      of the case and a review of the literature. RESULTS: The patient underwent
      successful excision of neurothekeoma and subsequent auricular cartilage graft
      reconstruction. Reconstruction failed to adequately heal at several months
      postoperatively and the defect was closed primarily. CONCLUSIONS: Rapidly growing
      nodules of the nose can have a broad differential and requires pathological
      diagnosis via early biopsy. This is important because the surgical approach
      varies depending on the lesion and its potential for metastasis and local growth.

PMID- 23172443
TI  - Correction of enophthalmos with rib bone segment and diced cartilage grafts.
AB  - We introduce our experiences of correcting enophthalmos with a rib bone segment
      graft and diced cartilage graft simultaneously.The affected orbit was exposed
      through a subcilliary incision, a medial brow incision, and a lateral brow
      incision. The periorbita was carefully dissected from the bony orbit
      circumferentially. The affected area was examined, and the size and shape of the
      bone graft were determined. A 5-cm incision was made at the 7th rib-cartilage
      junction, and the 7th and 8th ribs and costal cartilage was harvested as needed.
      The donor site was closed. The harvested rib bone segment was molded with a
      bender to fit the defect, and the cartilage was diced into 2 * 2 * 2-mm cubes.
      The diced cartilage was inserted into the subperiosteal space, and fibrin glue
      was sprayed.Nine patients (3 male and 6 female subjects) were operated on, and
      the average follow-up period was 9 months. On the exophthalmometry, the
      preoperative difference was 4.6 +/- 1.7 mm, and this improved to 1.4 +/- 0.8 mm
      at 3 months postoperatively. The average improvement was 3.2 mm.It is thought
      that the correction of enophthalmos by the combined use of a rib bone segment and
      cartilage grafts is very effective because bone and cartilage have complimentary
      effects in maintaining the globe's position.

PMID- 23172444
TI  - Tongue lymphangioma in adult.
AB  - Lymphangioma is a benign, hamartomatous tumor of the lymphatic channels. It is
      usually found in the head and neck region. Most lymphangiomas are present at
      birth and are usually diagnosed in infancy or early childhood. When lymphangioma
      occurs in the mouth, the anterior two thirds of the tongue is the most commonly
      affected region. A risk of secondary growth is classically described after
      surgical reduction. In this paper, we present 9 cases of tongue lymphangioma. We
      provide a literature review of tongue lymphangioma.

PMID- 23172445
TI  - Central serous chorioretinopathy after surgical repair of a blowout fracture.
AB  - We report the case of a 39-year-old male patient who experienced central serous
      chorioretinopathy after surgical repair of a blowout fracture. This patient
      developed bilateral central serous chorioretinopathy 1 week after surgical
      reconstruction of left medial and inferior orbital bone fractures. Fundus
      examination including fluorescein angiography and optical coherence tomography
      was performed. Central serous chorioretinopathy was more severe in the operated
      eye. Fortunately, the macular edema subsided, and the patient's vision normalized
      after 2 months without treatment.

PMID- 23172452
TI  - Mucocele in the buccal vestibule.

PMID- 23172453
TI  - Granular cell ameloblastoma of the anterior mandible.

PMID- 23172454
TI  - Isolated benign schwannoma of the supraorbital nerve presenting as an
      asymptomatic palpable mass.

PMID- 23172455
TI  - Lip nose surgery in a patient with hemophilia C (Rosenthal disease).

PMID- 23172456
TI  - Traumatic blindness due to explosion during traditional vinegar production.

PMID- 23172457
TI  - Aneurysmal bone cysts clinically mimicking a parotid gland mass.

PMID- 23172458
TI  - Nasal septal cyst:  a rare complication of nasal septal surgery.

PMID- 23172459
TI  - Pediatric lipoma of the buccal fat pad.

PMID- 23172460
TI  - Spindle cell carcinoma of the larynx following spindle cell pulmonary carcinoma: 
      second primary or metastasis?

PMID- 23172461
TI  - One-stage transfer of 2 paddles of thoracodorsal artery perforator flap with
      vascular anastomoses for Barraquer-Simons syndrome.

PMID- 23172462
TI  - Delayed thinning of the anterolateral thigh flap.

PMID- 23172463
TI  - Septoplasty decreases mean platelet volume levels in patients with marked nasal
      septal deviation.

PMID- 23172464
TI  - Congenital giant cervical teratoma.

PMID- 23172465
TI  - Implant handpiece with adapted drills in orthognathic surgery:  preventing facial
      scars.
AB  - The attachment of bilateral sagittal-split osteotomy of the mandibular ramus with
      bicortical screws or the combination of miniplates and a bicortical screw is
      complicated through the intraoral approach because of the angle required for
      insertion of screws, so it is necessary to use a trocater. This article aimed to
      report a technique developed and used in 60 patients, wherein an implant
      handpiece with adapted drills was used in the intraoral attachment. The setting
      was performed intraorally to prevent scarring and extraoral facial nerve damage,
      which may be caused by extraoral and transbuccal approaches routinely performed
      when using the trocater. The versatility of the handpiece implant allows for the
      insertion of monocortical and bicortical screws and rigid internal fixation of
      mandibular sagittal-split osteotomy, as well as surgical time reduction,
      decreasing postoperative morbidity.

PMID- 23172466
TI  - Surgical-orthodontic treatment for skeletal class II malocclusion with vertical
      maxillary excess, anterior open bite, and transverse maxillary deficiency.
AB  - Nongrowing adult patients with skeletal open bite have been considered among the
      most difficult to treat. This case report describes the surgical-orthodontic
      treatment of a blind 20-year-old woman who presented with skeletal class II
      malocclusion with vertical maxillary excess, anterior open bite, and transverse
      maxillary deficiency.After the transverse maxillary deficiency was corrected with
      miniscrew-assisted rapid palatal expansion, Le Fort I osteotomy with anterior
      segmental osteotomy and bilateral sagittal split ramus osteotomy with advancement
      genioplasty were used to correct the vertical maxillary excess and the anterior
      open bite. The patient's facial appearance was markedly improved, and she
      achieved a functional and stable occlusion after these treatments.This case
      report demonstrates the efficiency of miniscrew-assisted rapid palatal expansion
      for a patient with transverse maxillary deficiency and the benefit of a team
      approach using effective orthodontic mechanics in orthognathic surgery to correct
      a severe dentofacial deformity.

PMID- 23172468
TI  - Pathologic fracture of jaw in unicystic ameloblastoma treated with
      marsupialization.
AB  - Pathologic fractures may occur when a bone has been weakened by an underlying
      pathologic process. The treatment depends on the etiology. We report on a patient
      with pathologic fracture in the jaw caused by unicystic ameloblastoma. The lesion
      was subjected to marsupialization, and the size of the radiolucent lesion
      decreased. The fracture was consolidated by bone regeneration. For the remaining
      tumor, a secondary surgery was performed with enucleation followed by spray
      cryosurgery using a combination of propane, butane, and isobutane gases. The
      patient showed no signs of recurrence during the 3-year period after the second
      surgical procedure.

PMID- 23172467
TI  - Evaluation of a maxillary sinus floor augmentation in the presence of a large
      antral pseudocyst.
AB  - Sinus floor augmentation has been established as a predictable technique to
      overcome maxillary bone loss. Antral cystic lesions may lead to intrasurgical
      complications and should be accurately diagnosed. However, antral pseudocysts
      have recently been described not to be contraindicated for sinus-grafting
      procedures. The current article sought to report clinical, cone beam computed
      tomographic, and histologic results of a maxillary sinus floor augmentation,
      performed with piezoelectric surgery, in the presence of a large antral
      pseudocyst. Success of graft maturation was confirmed with histologic analysis,
      which also indicated the absence of inflammatory infiltration in the tissue
      evaluated. On the basis of our findings, it is possible to perform a predictable
      treatment based on sinus floor augmentation in the presence of antral
      pseudocysts. Graft maturation can also be achieved 6 months after sinus-lifting
      surgeries.

PMID- 23172469
TI  - Mandibular gunshot wound with bullet aspiration.
AB  - Urban violence continues to be an important source of penetrating craniofacial
      injuries in major trauma centers. Gunshot wounds to the mandible are a commonly
      treated condition by craniofacial surgeons. Some gunshot wounds are through-and
      through injuries, but in many patients, the bullet enters with no visible exit
      wound. In such situations, the bullet's trajectory and final destination are
      certainly important to the craniofacial surgeon in the extent of bony damage but
      may also be of unforeseen consequence to the patient's airway and respiratory
      condition. We present a case of a patient who had a gunshot wound to the face
      with comminuted mandibular ramus fracture in which the bullet was unexpectedly
      found to be aspirated down the right mainstem bronchus. This is the first
      reported case of a completely intact bullet being aspirated after gunshot wound
      to the face in an adult patient. We present this case to illustrate a rare
      possible complication after penetrating mandibular injury and offer a strategy
      for management of such an occurrence.

PMID- 23172470
TI  - Infantile fibromatosis of the pterygomandibular space.
AB  - Infantile fibromatosis (IF) is a benign, nonmetastasizing but locally aggressive
      tumor. Pterygomandibular space is deep and obscure, and IF in this space is
      seldom reported. We describe a typical case of IF in the pterygomandibular space
      that occurred in a 3-year-old girl. Intraoral incisional biopsy revealed the
      diagnosis of IF, and surgical resection of the tumor was performed. We intend to
      heighten the awareness of this tumor and emphasize the pathologic features and
      identifications of IF and discuss the diagnosis and treatment of this disease.
      For the high recurrence risk, follow-up with clinical examination and magnetic
      resonance imaging in pediatric patients is recommended.

PMID- 23172471
TI  - Cervicofacial emphysema after dental treatment with emphasis on the anatomy of
      the cervical fascia.
AB  - Fascial organization of the neck is quite complex and highly variable between
      individuals. Fascial layers separate very important structures in the neck, and
      by this way, they build anatomical walls against spread of infections, although
      this alignment could lead to spread of infection very easily throughout connected
      fascial spaces. We tried to discuss the possible anatomical pathways resulting in
      cervicofacial emphysema with a case.The development of cervicofacial emphysema
      after dental treatment is a well-known complication especially when using high
      speed turbines. A 39-year-old female patient is referred to our private dental
      clinic with complaints of swelling on her right supraclavicular region with edema
      of right orbita with absence of pain. In our case, emphysema reaches to
      supraclavicular region using retropharyngeal space and prevertebral fascia.This
      case illustrates anatomically how air or other materials, including pathogens or
      infections, could pass easily from oral cavity into thorax or even abdomen using
      facial planes.

PMID- 23172472
TI  - Tongue lesions.
AB  - BACKGROUND: Some authors have shown that tongue lesions represent an important
      segment of oral mucosal lesions group, with prevalence varying among
      epidemiologic studies from different countries. OBJECTIVES: The aim of this study
      was to describe the prevalence of tongue lesions in a Brazilian population.
      METHODS: A collaborative study was conducted using data from 5 anatomic pathology
      services in Brazil. After data collection, these tongue lesions were separated in
      4 groups: G1/malignant tumors, G2/benign tumors, G3/reactive lesions, and
      G4/other lesions. RESULTS: Analysis of 6231 specimens for which oral biopsy was
      performed showed 760 cases (12.2%) diagnosed in the tongue. From this total, 306
      cases (40.3%) occurred in females, and 454 (59.7%) occurred in males. Ages ranged
      from 3 to 93 years, with a global average of 45.3 years. The largest numbers of
      cases were represented by reactive lesions (44.6%), followed by benign tumors
      (27.9%), malignant tumors (18.6%), and other lesions (8.9%). CONCLUSIONS: Tongue
      diseases were more common in male patients, and most of them were reactive
      lesions or benign neoplasms, but 18.6% were malignant neoplasms. The occurrence
      of malignant neoplasm increased notably with age.

PMID- 23172473
TI  - Human heart by art.
AB  - Heart is of great importance in maintaining the life of the body. Enough to stop
      working for a few minutes to cause death, and hence the great importance in
      physiology, medicine, and research. This fact was already emphasized in the Bible
      in the Book of Proverbs, chapter 4 verse 23: "Keep your heart with all diligence,
      for out of it is the wellspring of life." Art was able to demonstrate the heart
      from various aspects; realistically, as done by Leonardo de Vinci who
      demonstrated the halves of the heart and its blood vessels. Symbolically, as a
      source of life, the heart was demonstrated by the artist Mrs. Erlondeiel, as a
      caricature by Salvador Dali, as an open heart by Sawaya, etc. Finally, it should
      be emphasized that different demonstrations of the human heart by many artworks
      make this most important organ of our body (that cannot be seen from outside)
      more familiar and clearer to us. And this is the purpose of this article-to
      demonstrate the heart through a large number of artworks of different kinds.

PMID- 23172474
TI  - Rapidly progressive thyroid mass:  amyloid goiter.
AB  - Amyloidosis is a disease of unknown etiology characterized by the accumulation of
      an amorphous proteinaceous material in various organs and tissues of the body.
      Amyloid goiter is an exceedingly rare pathologic condition due to massive amyloid
      infiltration of the thyroid tissue. Amyloid goiter occurs in association with
      both primary and secondary systemic amyloidosis, more commonly in the latter.
      Preoperatively, it simulates a multinodular goiter, and surgical intervention is
      often necessary to establish a diagnosis and to relieve compressive symptoms of a
      neck mass. We present the case of an 85-year-old female patient who presented
      with a rapidly enlarging goiter. Histologic examination confirmed amyloid goiter.

PMID- 23172475
TI  - Inflammatory myofibroblastic tumor of the parotid gland.
AB  - An inflammatory myofibroblastic tumor, previously known as an inflammatory
      pseudotumor, is an uncommon neoplasm. This tumor, which has characteristic
      morphologic and immunohistochemical features, is mostly seen in the lung. We
      present a rare case of an inflammatory myofibroblastic pseudotumor of the parotid
      gland. A 45-year-old woman presented with a 4-month history of a swelling in her
      right parotid region. A partial parotidectomy with preservation of the facial
      nerve branches was performed. The incidence of inflammatory myofibroblastic tumor
      in the parotid gland is low, and local resection is currently the best treatment.
      A prolonged postoperative follow-up period is necessary for patients with
      inflammatory myofibroblastic tumor. Inflammatory myofibroblastic tumor of the
      parotid gland is discussed with a brief literature review.

PMID- 23172476
TI  - Nodular fasciitis in the maxillary region.
AB  - We describe the imaging and histologic findings of a case of nodular fascitiis in
      the maxillary region in a 54-year-old man. The rapid growth and tissue distortion
      of this lesion may mimic malignant tumors. Therefore, proper diagnosis is
      essential to avoid unnecessarily aggressive treatment.

PMID- 23172477
TI  - Surgical management of pathologic mandibular fractures.
AB  - BACKGROUND: The aim of this article was to present our experience in the
      management of pathologic mandibular fractures. METHODS: We conducted a
      retrospective analysis of 14 patients with pathologic mandibular fractures
      associated with osteoradionecrosis, bisphosphonate-related osteonecrosis of the
      jaw, benign/malignant lesions, osteomyelitis, idiopathic, or iatrogenic etiology.
      Data collected included age, sex, etiology, site, treatment, and outcome.
      RESULTS: Five patients had iatrogenic fractures, 3 patients had osteomyelitis, 2
      had benign cystic lesion, and the remaining 4 had primary squamous cell
      carcinoma, histiocytosis, multiple myeloma, and bisphosphonate-related
      osteonecrosis of the jaw, respectively. Eleven fractures of 14 were treated using
      a 2.4-mm mandibular plate. CONCLUSIONS: Pathologic mandibular fractures may be
      challenging to treat because of their different etiology and peculiar local and
      general conditions, often requiring a more rigid fixation. In patients with poor
      medical conditions, simpler and more limited options may be preferred.

PMID- 23172478
TI  - Subgaleal-subperiosteal flap for forehead and scalp reconstruction.
AB  - Forehead soft tissue defects are most usually associated with motor vehicle
      accident and less commonly with physically assault, trauma resulting from falls,
      malignant tumor resection, and burn injury. These kinds of defects incorporate
      only the soft tissue in general but sometimes there are accompanying bone
      defects. Different reconstruction alternatives can be preferred depending on the
      defect type and the amount of tissue loss. In this report, a patient who
      underwent surgery for tumor excision is presented. After surgical excision,
      denuded frontal bones were covered with subgaleal-subperiosteal flap. Split
      thickness skin graft harvested from the medial upper arm was used for skin
      resurfacing. Optimal healing and cosmetic outcome were obtained using 1-step
      surgical procedure.

PMID- 23172479
TI  - An unusual mass filling within the middle meatus.
AB  - Schwannoma is a benign tumor that originates from sheath of myelinated peripheral
      nerves, rarely seen at the nasal cavity and paranasal sinuses. Symptoms of this
      tumor are nonspecific, and diagnosis is often made only after histological
      examination. Schwannoma is radioresistant, and chemotherapy is not effective, so
      surgical resection is the only curative treatment for this tumor. Endoscopic
      sinus surgery was the first choice for this case because of its definite origin
      and being easy to remove for complete excision. We present a patient with
      schwannoma who underwent an endonasal endoscopic approach for complete resection.

PMID- 23172480
TI  - Quantitative survey on the same shape of nose for women and men.
AB  - The present article is a follow-up to a previous article published in this
      magazine entitled "Numerical survey of the different shapes of human nose". In
      this article, experimental results were reported for the numerical quantities of
      the different shapes of nose for men and women together. To the best of the
      author's knowledge, this approach has never been applied. In the present article,
      a quantitative difference of the same shape of nose is presented for women and
      men separately.

PMID- 23172481
TI  - Management of an unusual presentation of Ascher syndrome.
AB  - Ascher syndrome is defined by the association between double lip,
      blepharochalasis, and nontoxic goiter. Because it is a rare disease, it is most
      often misdiagnosed, despite its implications for quality of life. We report a
      variation of an incomplete type of Ascher syndrome affecting the upper lip, upper
      eyelids, and lateral canthi of a young male patient. The surgical management,
      follow-up, and a brief overview of the syndrome are described. The results
      presented show an aesthetic and functional improvement of the facial deformities.

PMID- 23172482
TI  - Tissue engineering with dental pulp stem cells:  isolation, characterization, and
      osteogenic differentiation.
AB  - INTRODUCTION: Dental pulp stem cells (DPSCs) are adult mesenchymal stem cells
      that have the ability to differentiate into osteoblasts, a fact that is very
      interesting in the context of tissue engineering. Our purpose was to isolate and
      characterize DPSCs and to compare the differentiation potential of 3 different
      osteogenic media. PATIENTS AND METHODS: Human dental pulp extracted from healthy
      young adults was placed in flasks with a mesenchymal expansion medium. At passage
      4 DPSCs were analyzed for cell-cycle stage, proliferation, viability, and
      immunophenotype. DPSCs were grown in 3 different osteogenic media for 40 days.
      Flasks were incubated at 37  degrees C in 5% CO2, and the medium was changed
      twice a week. At day 40, the mineralization of the matrix was determined with
      Alizarin Red S dye. RESULTS: After osteogenic induction, DPSCs developed
      mineralization nodules (clusters), as revealed by Alizarin Red staining. This
      staining was stronger in the Osteodiff (Miltenyi) medium when compared to the
      other osteogenic media. CONCLUSIONS: This study demonstrates the ability of DPSC
      to differentiate into osteoblasts, especially in the presence of Osteodiff
      (Miltenyi). DPSCs are therefore a good candidate model for the study of hard
      tissue mineralization.

PMID- 23172483
TI  - Optical impression systems for CAD-CAM restorations.
AB  - Computer-aided design/computer-aided manufacturing images can be taken through
      either direct or indirect imaging. For the indirect systems, the digitalization
      is obtained from the impression material or cast, and for the direct ones the
      image is taken directly from the mouth using intraoral scanners.The direct
      acquisition systems have been constantly improved because these are less
      invasive, quicker, and more precise than the conventional method. Besides, the
      digital images can be easily stored for a long time. Therefore, the aim of this
      paper was to describe and discuss based on the literature the main direct image
      acquisition systems available on the market: CEREC Bluecam (Sirona), Lava C.O.S.
      System (3M ESPE), iTero System (Cadent/Straumann), and E4D System (D4D
      Technologies).

PMID- 23172484
TI  - Successful reconstruction after resection of malignant eccrine poroma using
      retroauricular artery perforator-based island flap.
AB  - INTRODUCTION: Malignant eccrine poroma (MEP), or porocarcinoma, is a rare
      malignant tumor arising from the intraepidermal eccrine duct. It has propensity
      to arise on the lower limbs (44%), trunk (24%), or head and neck region (24%) but
      rarely occurs on the scalp. It is very difficult to find proper technique for the
      first time. In this paper, we introduce rare MEP developing in a longstanding
      eccrine poroma on the scalp (postauricular area) and successful reconstruction
      method using perforator-based island flap. PATIENT AND METHODS: A 52-year-old man
      who had an abrupt growth of a mass on the temporal area presented to us. It was a
      3.7 * 2.1-cm mass with fungated margin, but it does not involve the perivertebral
      muscle and fat tissues in computed tomography scan. The next we executed was
      general operation for wide excision and scalp reconstruction of a large
      postauricular defect using retroauricular artery perforator-based island flap.
      RESULT: We harvested 7 * 5 cm sized flap and donor site closed primarily without
      any skin graft. We found that the flap had mild congestion after the suture and
      mild fullness because of swelling. CONCLUSIONS: Retroauricular artery perforator
      based island flap can survive over the bone, protect the infection, and bear the
      radiological treatment. Aesthetically, the patient was very satisfied with the
      result: similar skin texture, color, thickness, and pliability. There was only a
      linear scar on the lower margin of the mandible.

PMID- 23172485
TI  - Management of obstructive sleep apnea by maxillomandibular advancement surgery in
      an edentulous patient.
AB  - BACKGROUND: Maxillomandibular advancement (MMA) surgery is a surgical treatment
      option for treating the patients with obstructive sleep apnea (OSA). Surgical
      treatment of OSA by MMA surgery is a problem when it is encountered with an
      edentulous patient because of the intermaxillary fixation problem of the jaws. A
      paucity of information is available concerning MMA surgery for edentulous
      patients. MATERIALS AND METHODS: In this case report, we present the preoperative
      planning, orthognathic surgery, and postoperative phases of a 49-year-old
      edentulous severe OSA (apnea hypopnea index, 81.9 event/hr) patient who underwent
      MMA surgery. RESULTS: Polysomnographic examination 9 months after surgery
      revealed normalization of the somnographic evaluations (apnea hypopnea index,
      1.3). CONCLUSIONS: The results reported in the present case showed that the
      surgical treatment of OSA by MMA surgery in edentulous patients could be
      successfully done. Further critical evaluations of this approach for the surgical
      treatment of edentulous OSA patients are needed.

PMID- 23172486
TI  - Multifocal lipoblastoma of the face.
AB  - Lipoblastoma is a rare benign neoplasm found exclusively in the pediatric
      population that can occur anywhere in the body, most commonly seen in the
      extremities but also found in the face. We report an 8-month-old female subject
      who presented with multifocal soft tissue masses of the face. The diagnosis of
      lipoblastoma was made in 2 separate locations after surgical resection.
      Subsequent surgery was performed at the cheek site in an attempt to remove
      further mass, resulting in discovery of 2 other discrete tumors found to be
      lipoblastomas. Although the literature reports recurrence rates ranging from 14%
      to 27%, to our knowledge, aside from a case of Proteus syndrome, there are no
      known reports of multiple lipoblastomas in the literature. Presentation of the
      case, review of pertinent literature, and consideration of congenital
      infiltrative lipomatosis of the face follow.

PMID- 23172487
TI  - Changes in complete blood count in patients with surgically treated facial
      fractures.
AB  - The purpose of this prospective study was to verify the changes in the
      preoperative and postoperative complete blood counts of patients with surgically
      treated facial fractures. Fifty consecutive patients with a mean age of 34 years
      who presented facial fractures and underwent surgical treatment were included. A
      complete blood count was performed, comprising the red and white blood cell count
      (cells/MUL), hemoglobin (g/dL), and hematocrit (%) levels. These data were
      obtained preoperatively and postoperatively during a 6-week period. Statistical
      analyses were performed using the Kruskal-Wallis and Mann-Whitney tests to
      identify the possible differences among the groups and among the periods of
      observation using the Friedman and Wilcoxon matched-pairs signed-ranks tests. The
      most common location of the fractures was the mandible (42.3%), followed by the
      zygomatic-orbital (36.5%) and associated locations (21.2%). Leukocytosis was
      associated with neutrophilia in the immediate postoperative period in all of the
      groups. There were no values below the reference limits of the values of
      hemoglobin, hematocrit, and erythrocytes, and no values above the reference
      limits for the remaining white blood cells, although significant differences
      among periods were observed in most cells, depending on the type of fracture. The
      primary findings were leukocytosis associated with neutrophilia, verified in the
      immediate postoperative period in all of the groups, and the influence of the
      type of fracture on the significant alterations observed among studied periods on
      the values of hemoglobin, hematocrit, erythrocytes, leukocytes, neutrophils, and
      lymphocytes.

PMID- 23172488
TI  - Acrylic cranial implant:  an alternative vector in management of cranial defect.
AB  - In a pediatric patient with cranial defect, in order to replace the missing
      portion of the cranium, an acrylic cranial implant was fabricated prior to the
      surgical procedure. The primary aim was to fabricate this cranial implant prior
      to the surgical procedure and with optimum fit. A customized hand-sculpted
      acrylic cranial implant fabricated by lost wax technique was made prior to the
      surgery and with adequate precision.The prefabricated cranial implant was used by
      neurosurgeons on the patient in order to restore the continuity of bone (by the
      acrylic cranioplast) over the cranial defect, improving the aesthetics and more
      importantly providing protection to the vital neural tissue.Though with recent
      advancements (like computer-aided design and manufacturing, and rapid
      prototyping), rapidity and precision can be achieved in the fabrication of
      cranial prosthesis, yet most of the apparatus may not be amenable in every setup
      and may not be affordable by all patients. A simple, operator-friendly technique
      which acquires satisfactory precision has been described for a patient much in
      need. Optimal postoperatory results were attained.

PMID- 23172489
TI  - Anterior superficial temporal artery island flap:  intraoral defect repair.
AB  - There are many options for the repair of intraoral defects. Today, free radial
      forearm or anterolateral thigh perforator flap is the first choice for the repair
      of intraoral defects. However, the importance of regional flaps is still
      maintained for patients whose medical condition is inappropriate for a long
      surgery and anesthesia time. In this report, we present our clinical experience
      with 9 patients who underwent retromolar trigone, buccal mucosal, gingival, and
      mouth floor reconstruction with anterior superficial temporal artery island flap
      (ASTIF) which has not been described in the literature before. Their mean age is
      49 (27-85) years. ASTIF dimensions used for the reconstructions ranged from 3 * 5
      to 8 * 16 cm. No partial or total flap necrosis was seen in any of the patients;
      only 3 patients had venous congestion problem for the first 3 days of the
      surgery, but they all healed well. Five patients had squamous cell carcinoma, 2
      patients had squamous cell carcinoma with local recurrence, 1 patient had
      adenocarcinoma, and 1 patient had mandibular osteocarcinoma. Patients were
      followed for a minimum of 6 months postoperatively (average 12 months, range 6 to
      24 months). ASTIF provides an excellent alternative for reconstructing defects of
      the oral cavity for some patients who have significant comorbid conditions or
      specific contraindications to free tissue transfer. At the same time, the
      combination with the free flaps increases the success of the restoration. LEVEL
      OF EVIDENCE: Level IV therapeutic study.

PMID- 23172490
TI  - Initial finding of mandible mass in multiple myeloma.
AB  - Multiple myeloma is characterized by a monoclonal neoplastic proliferation of
      plasma cells. Systematically, multiple myeloma would bring on hypercalcemia,
      anemia, renal failure, and bone lesions. The vertebrae, ribs, pelvic bone, and
      skull are usually involved in bone lesions. We report a 46-year-old man whose
      initial finding of multiple myeloma was a mandible mass. Mandible mass is not
      rare in multiple myeloma, but it is not that frequently seen as an initial
      finding.

PMID- 23172491
TI  - Does the titanium plate fixation of symphyseal fracture affect mandibular growth?
AB  - The effect of metallic fixation on growth is a major concern in children and is
      not yet clear. The aim of this study was to evaluate the effect of metallic
      fixation of mandibular symphyseal fracture on mandibular growth.Eighteen 90-day
      old growing white New Zealand rabbits weighing 1.6 to 2.5 kg were included in
      this study and divided into 2 groups of 9 subjects. In the experimental group,
      animals underwent mandibular osteotomy, simulating a symphyseal fracture on the
      midline of mandibular symphysis. The bone segments were fixed with microplates
      and microscrews (1.6 mm).In the control group, the same surgical incision without
      performing symphyseal osteotomy was conducted, and 2 screws were inserted on each
      side of the symphyseal midline.Digital cephalometric and submentovertex
      radiographs were taken before the operation and at postoperative 6 months for
      each animal in 2 groups, and cephalometric measurements were performed. The
      distance between the centers of the head of 2 screws measured at the end of
      surgery in the control group was compared with measurements at 6 months after
      surgery. Obtained data were statistically analyzed.There is no statistically
      significant difference between the 2 groups for growth amount of both sides of
      the mandible. Difference of ANS-Id (the most anterior points of nasal bone, the
      most anterior point on the alveolar bone between the lower incisors) and Cd-Id
      (the uppermost and most distal point of the mandibular condyle, the most anterior
      point on the alveolar bone between the lower incisors) values of the 2 groups is
      not statistically significant (P > 0.05).The distance between the 2 screws at the
      first application significantly increased at the postoperative sixth month (P <
      0.05). Metallic fixation of mandibular symphyseal fracture does not affect the
      vertical and sagittal mandibular growth in growing rabbits.

PMID- 23172492
TI  - Surgical treatment of periorbital foreign body.
AB  - We present the rare case of a violence-related accident involving a periorbital
      foreign body and surgical treatment. A 43-year-old man was brought to the
      hospital with a foreign body lodged in his left eyelid. A ballpoint pen
      penetrated the upper lid and orbital floor and reached the maxillary sinus.The
      spring of the ballpoint pen was observed in the radiograph, but the other parts
      of the ballpoint pen were not seen.The ballpoint pen was retrieved along the path
      of insertion. The fractured part of the orbital floor was slightly enlarged with
      a drill to allow visual access during surgery. Plastic pieces and the spring of
      the pen were removed under endoscopy inside the maxillary sinus. The inferior
      orbital wall was successfully reconstructed and there were no postoperative
      complications.The unique features of this case include the nature of the foreign
      body and its trajectory; removal was particularly challenging because the foreign
      body was not clearly visible in the radiograph.

PMID- 23172493
TI  - Fascia versus cartilage graft in type I tympanoplasty:  audiological outcome.
AB  - Various materials such as fascia, perichondrium, and cartilage have been used for
      reconstruction of the tympanic membrane in middle ear surgery. Because of its
      stiffness, cartilage is resistant to resorption and retraction. However,
      cartilage grafts result in increased acoustic impedance, the main limitation to
      their use. The aim of this study was to compare the hearing results after
      cartilage tympanoplasty versus fascia tympanoplasty. This study included 114
      patients without postoperative tympanic membrane perforation who underwent
      tympanoplasty type I between 2007 and 2010, 31 with fascia and 83 with cartilage.
      Preoperative and 1 year postoperative air-bone gap (ABG) and postoperative gain
      in ABG at frequencies of 0.5, 1, 2, and 3 kHz were assessed. Both groups were
      statically similar in terms of the severity of middle ear pathology and the
      preoperative hearing levels. Overall, postoperative successful hearing results
      showed 77.4% of the fascia group and 77.1% of the cartilage group. Mean
      postoperative gains in ABG were 9.70 dB for the fascia group and 9.78 dB for the
      cartilage group. These results demonstrate that hearing after cartilage
      tympanoplasty is comparable to that after fascia tympanoplasty. Although
      cartilage is the ideal grafting material in problematic cases, it may be used in
      less severe cases, such as in type I tympanoplasty, without fear of impairing
      hearing.

PMID- 23172494
TI  - Effect of mitomycin C on revision endoscopic dacryocystorhinostomy.
AB  - OBJECTIVE: The objectives of the study were to compare the outcome and success
      rate of revision endoscopic dacryocystorhinostomy (EN-DCR) with or without use of
      adjunctive mitomycin C (MMC) in cases with dacryocystorhinostomy (DCR) failure.
      METHODS: Thirty-six consecutive adult patients underwent revision EN-DCR. The
      patients were divided into 2 groups. In group 1 (18 patients), a neurosurgical
      cottonoid soaked in MMC at 0.5 mg/mL was placed at the osteotomy site for 5
      minutes (using canalicular silicone intubation tube). In the other group (18
      patients), standard endoscopic dacryocystorhinostomy technique was used without
      MMC (using canalicular silicone intubation tube). Successful DCR was defined as
      relief of symptoms (resolution of epiphora and absence of discharge) as
      demonstrated by saline irrigation at the last postoperative visit. RESULTS: The
      EN-DCR procedure with adjunctive MMC was successful in 16 (88.88%) cases. The
      mean follow-up was 11.5 months (7-19 months). No significant complications were
      encountered. In the control group, the EN-DCR was successful in 10 patients
      (55.55%). The mean follow-up was 12.7 months (6-22 months). The difference
      between the 2 groups was statistically significant (P < 0.05). CONCLUSIONS:
      Recurrent nasolacrimal duct obstruction after primary DCR is mainly due to
      reclosure of the nasolacrimal stoma and osteotomy site with granulation tissue.
      Adjunctive use of intraoperative MMC seems to be a safe adjuvant that could help
      in increasing the success rates of revision EN-DCR surgery.

PMID- 23172495
TI  - Role of allergy in children with adenotonsillar hypertrophy.
AB  - OBJECTIVE: The goal of this prospective study is to investigate the correlation
      between allergen sensitivity and radiographic evaluation of adenoidal obstruction
      and tonsil size. SUBJECTS AND METHODS: A total of 82 children with upper airway
      obstructive symptoms were evaluated for their tonsil size. All patients underwent
      digital lateral soft tissue radiographs. Assessment of nasopharyngeal obstruction
      in radiographs was done according to the Cohen and Konak method. Skin prick tests
      with multitest applicator including 14 allergens were carried out to investigate
      their allergic background. RESULTS: All children reacted positive to at least one
      of the 14 allergens tested. We found a statistically significant correlation
      between tonsil size and skin prick tests (P < 0.01). However, there was no
      statistically significant correlation between the adenoid size and skin prick
      test results (P > 0.05). CONCLUSIONS: Although the degree of nasopharyngeal
      obstruction caused by adenoid hypertrophy does not increase with the degree of
      positivity to specific allergens in skin prick tests, allergic sensitivity may
      play an important role in children with tonsillar hypertrophy.

PMID- 23172496
TI  - Small cell lung cancer with metastasis to the thyroid in a patient with toxic
      multinodular goiter.
AB  - Thyroid metastasis of lung cancer is rarely observed in clinical practice. The
      primary cancers which metastasize to the thyroid gland are mostly renal cell
      carcinoma, lung cancer, and breast cancer. Transient destructive thyrotoxicosis
      is caused by massive metastasis of extrathyroid tumors. We herein present a case
      report of a patient with small cell carcinoma of lung with metastasis to the
      thyroid and thyrotoxicosis due to toxic multinodular goiter. A 66-year-old man
      complained of swelling around the right side of the neck, dyspnea, progressive
      weight loss, and palpitation starting since 3 months before his admission. The
      patient was diagnosed with small cell carcinoma of lung with metastasis to the
      thyroid and thyrotoxicosis due to toxic multinodular goiter. The case report
      presented here illustrates the challenge of making a definitive and adequate
      diagnosis, particularly if the patient presents with 2 potential causes of
      thyrotoxicosis. Thyroid scintigraphy is an important tool for differential
      diagnosis of thyrotoxicosis.

PMID- 23172497
TI  - Aesthetic mental and cervical reconstruction after severe acne inversa by using a
      bilateral pedicled expanded forehead flap.
AB  - Acne inverse (AI), also known as hidradenitis suppurativa, is characterized by
      inflammatory nodules, fistulating sinus tracts, and painful skin abscesses. The
      severe AI often produces disfiguring scars influenced in both the appearance and
      function, especially in the facial and cervical regions. There might be
      difficulties in the situation for surgical treatment. This report described a 26
      year-old man with severe scarring contractures in the neck and mandible regions
      after a long-term AI treated successfully with a bilateral pedicled expanded
      forehead flap. With the achievement of mental cervical angle, the patient has
      been reconstructed well both aesthetically and functionally during the long-term
      follow-ups.

PMID- 23172498
TI  - Reconstruction of chronic osteomyelitis of the nose using a thin latissimus dorsi
      perforator flap.
AB  - Osteomyelitis is an acute or chronic inflammatory process that occurs in bone.
      Although cranial bones are rarely involved, timely diagnosis and early treatment
      are mandatory because of its proximity to critical neurovascular structures and
      aesthetic considerations.A 57-year-old woman, who had a comminuted open nasal
      bone fracture 20 years ago, presented a firm, painful swelling nose. Whole-body
      bone scan images indicated increased uptake of the nasal bone, which was
      suspected to be osteomyelitis. After debridement, the nose was reconstructed with
      a thin latissimus dorsi perforator flap.In this article, we report a rare case of
      chronic osteomyelitis of the nose and provide a brief review of the literature.
      It is important for clinicians to consider osteomyelitis for early diagnosis and
      treatment.

PMID- 23172499
TI  - Radiation-induced fibrosarcoma after radiotherapy for osteosarcoma in the
      mandibular condyle.
AB  - With recent improvements in survival duration after cancer treatment, it is
      becoming increasingly important to study treatment-related morbidity and
      mortality. Radiation-induced sarcomas in the irradiated field are well-known
      potential late sequelae of radiotherapy. These tumors are biologically
      aggressive. In the case described here, a radiation-induced fibrosarcoma appeared
      at 20 years after initial surgery, radiotherapy, and chemotherapy for an
      osteosarcoma of the mandibular condyle. Radiation-induced fibrosarcoma is
      relatively rare in the head and neck region. The details of this case are
      presented, and diagnostic and management considerations are described.

PMID- 23172500
TI  - Lipostructure in Parry-Romberg disease.
AB  - Parry-Romberg syndrome is a disease characterized by progressive hemifacial
      atrophy. Multiple surgical procedures have been used to improve the facial volume
      and contours of patients with this disease, including alloplastic, silicone, or
      collagen implants; lipofilling; and pedicled or free-flap transplants. The
      present case describes the successful application of lipostructure to treat a
      woman with Parry-Romberg syndrome affecting the left side of her face.

PMID- 23172501
TI  - Evaluation of upper airway dimensional changes and hyoid position following
      mandibular advancement in patients with skeletal class II malocclusion.
AB  - BACKGROUND: Class II skeletal malocclusion due to mandibular deficiency is
      considered a risk factor for sleep disorders due to oropharyngeal airway
      deficiencies. In view of the above, a prospective interventional study was
      undertaken to evaluate upper airway dimensional changes and position of hyoid
      bone by comparing pretreatment and posttreatment lateral cephalograms. The
      objective also included the establishment of the ratio of mandibular advancement
      to increase in airway dimensions. PATIENTS AND METHODS: Pretreatment and
      posttreatment lateral cephalograms of 20 adults (13 females and 7 males) with
      skeletal class II malocclusion treated by combined orthodontics and bilateral
      sagittal split ramus osteotomy was evaluated for changes in posterior airway
      space (PAS), superior airway space (SAS), minimum airway space (MAS), hyoid bone
      position (MP-H), effective mandibular length (Co-Gn), mandibular corpus length
      (Go-Pg), and pogonion position (N perpendicular-Pg). The cephalograms were
      manually traced by a single operator and the data analyzed using MINITAB 13.2
      version software. RESULTS: There was a statistically highly significant (P =
      0.0001) increase in PAS, SAS, MP-H, Co-Gn, and Go-Pg. The mean ratio of
      mandibular advancement to increase PAS, SAS, and MAS was 1:0.35, 1:0.34, and
      1:0.24, respectively. Hyoid bone moved superiorly and in an anterior direction by
      2.1 +/- 2.8 mm and was found to be statistically highly significant (P = 0.0001).
      CONCLUSIONS: The study showed an overall increase in airway dimension and
      improvement in hyoid position. Thus, the procedure may be considered beneficial
      in reducing upper airway collapsibility and preventing sleep disorders due to
      oropharyngeal airway deficiencies in skeletal class II malocclusion.

PMID- 23172502
TI  - Total nasal prosthesis after resection of a recurrence of skin carcinoma on a
      forehead flap in a post-rhinectomy site.
AB  - The nose is the most common site for facial skin cancer; nonmelanoma skin cancers
      are the most common tumors of this region. Median and paramedian forehead flaps
      have been proposed for nasal defects greater than 2.5-3 cm in diameter. The aim
      of this study was to describe a peculiar case of a recurrence of a squamous cell
      carcinoma in a forehead flap of a post-rhinectomy site managed by a fabrication
      of a total nasal prosthesis as salvage procedure. To the best of our knowledge,
      this is the first reported case in the scientific literature of a recurrence of a
      squamous cell carcinoma in a forehead flap of a post-rhinectomy site; this
      peculiar clinical report adds knowledge in the complex field of nasal
      reconstruction.

PMID- 23172503
TI  - Application of the "All-on-Four" concept and guided surgery in a mandible treated
      with a free vascularized fibula flap.
AB  - In this article, we describe the first case in the literature in which 3D
      computer-assisted treatment planning and guided surgery enabled a patient
      affected by extreme paraphysiologic mandibular bone atrophy to be treated with a
      free vascularized fibula flap and, after a period of healing, the flapless
      installation of 4 immediately loaded dental implants. The computer-fabricated
      surgical guide allowed placement of the implants according to the "All-on-Four"
      concept in a proper spatial preplanned position and by tilting 1 implant,
      avoiding an area of bone discontinuity. Additionally, this technique allowed the
      production of a prefabricated temporary prosthesis, delivered after implant
      insertion, which could be immediately loaded. The use of a fibula flap makes it
      possible to create greater bone thickness while computer-assisted treatment
      planning and guided surgery provide several advantages over the traditional
      technique.

PMID- 23172504
TI  - Evaluation of torque maintenance of abutment and cylinder screws with Morse taper
      implants.
AB  - The screw loosening of implant-supported prostheses is a common mechanical
      failure and is related to several factors as insertion torque and preload. The
      aim of this study was to evaluate the torque maintenance of retention screws of
      tapered abutments and cylinders of Morse taper implants submitted to retightening
      and detorque measurements. Two groups were obtained (n = 12): group I-tapered
      abutment connected to the implant with titanium retention screw and group II
      cylinder with metallic base connected to tapered abutment with titanium retention
      screw. The detorque values were measured by an analogic torque gauge after 3
      minutes of torque insertion. The detorque was measured 10 times for each
      retention screw of groups I and II, totalizing 120 detorque measurements in each
      group. Data were submitted to ANOVA and Fisher exact test (P < 0.05). Both groups
      presented reduced detorque value (P < 0.05) in comparison to the insertion torque
      in all measurement periods. There was a statistically significant difference (P <
      0.05) between the detorque values of the first measurement and the other
      measurement periods for the abutment screw. However, there was no statistically
      significant difference (P > 0.05) for the detorque values of all measurement
      periods for the cylinder screw. In conclusion, the abutment and cylinder screws
      exhibited torque loss after insertion, which indicates the need for retightening
      during function of the implant-supported prostheses.

PMID- 23172505
TI  - One-stage treatment of hemimandibular hyperplasia.
AB  - Hemimandibular hyperplasia (HH) is a rare, self-limiting process manifesting
      between the first and third decades of life. HH causes facial asymmetry and
      derangement of the occlusion. Management involves resection of the condylar head
      and orthognathic surgery. This paper describes the case of a 38-year-old woman
      with spontaneous onset HH over a span of approximately 30 years. The condition
      was managed with resection of the condyle with simultaneous orthognathic surgery.
      The patient is currently satisfied with her appearance and function, and there
      are no signs of recurrence after 2 years.

PMID- 23172506
TI  - A nasal dermal sinus cyst involving the nasal septum.
AB  - Nasal dermoid sinus cysts (NDSCs) are rare neoplasms in the median line of the
      nasofrontal area. Unlike other dermoid cysts, a NDSC can manifest as a cyst,
      sinus, or fistula, and may extend intracranially. They usually occur as a mass in
      the median nasofrontal area and may have a pit. As an extensive tract can appear
      in some cases, careful preoperative evaluation and complete excision are
      required. A 15-year-old boy presented with a fistula, present from birth, in the
      nasal soft triangle. This report describes a case of NDSC occurring in the nasal
      septum and a fistula opening in the soft triangle, which is very rare, without
      recurrence after 4 years.

PMID- 23172507
TI  - Decompression for management of keratocystic odontogenic tumor in the mandible.
AB  - Keratocystic odontogenic tumor (KCOT) is a benign intraosseous neoplasm of
      odontogenic origin with high recurrence rate. To date, various conservative or
      aggressive management strategies have been suggested as a method of treatment.
      Decompression is a conservative method that has been used in the treatment of
      large odontogenic cysts. The present paper reports a case of KCOT located in the
      mandible and discusses the importance of its management using conservative
      methods. The authors present a case of a 38-year-old patient with a KCOT located
      in the right mandibular angle and ascending ramus, which was treated by
      decompression followed by enucleation and curettage. The lesion did not recur
      during a follow-up period of 3 years after surgery. Preserving important
      structures of the bone and soft tissue decompression is a method with low
      morbidity. In addition, according to the literature, decompression has a success
      rate at least as high as the one of most aggressive treatments.

PMID- 23172508
TI  - Orbital roof reconstruction using porous polyethylene sheet with embedded
      titanium.
AB  - Calvarial defects, including the orbital roof defect that occurs after trauma or
      oncologic resection, require immediate reconstruction to avoid complications such
      as enophthalmos, diplopia, and transmission of the cerebral pulse to the eye. In
      these cases, autologous bone grafts or various alloplastic materials have been
      used.Between January 2010 and December 2010, 5 patients underwent surgery for
      orbital roof reconstruction using porous polyethylene sheet with embedded
      titanium, which was developed for reconstruction of inferomedial wall of the
      orbit. One patient underwent surgery because of tumor excision; the other
      patients, because of trauma. Two patients had intracranial hemorrhage and 3
      patients had a defect in the supraorbital rim. We reconstructed the supraorbital
      rim and the orbital roof using a combination of calvarial bone graft and the
      porous polyethylene sheet with embedded titanium. The sheet was bended and
      trimmed according to the shape of the orbital defect, and it was fixed on the
      remaining adjacent bone using a microplate.There were no complications during the
      follow-up period. The patients were satisfied with the external appearance.In
      conclusion, the orbital roof reconstruction using porous polyethylene sheet with
      embedded titanium was an easy and a time-efficient procedure with satisfactory
      results.

PMID- 23172509
TI  - An unusual presentation of pleomorphic adenoma:  nasal ala.
AB  - Pleomorphic adenomas arising from nonsalivary glands are not common, whereas they
      are the most common of all salivary gland tumors. They have been reported to
      arise from the nasal septum, maxillary sinus, lacrimal gland, etc. However, no
      cases of pleomorphic adenoma involving the nasal ala have been reported. We
      present a case of pleomorphic adenoma arising from a nasal ala. The adenoma was
      excised without causing any deformity and there was no recurrence during a 6
      month follow-up.

PMID- 23172510
TI  - Surgical management of a rare variant of submucous cleft palate.
AB  - A submucous cleft is a palatal defect that is bridged over by mucosa; such a
      defect has been recognized for many years. A small portion of all cleft palate
      defects shows this phenomenon, but the cryptic nature of the lesion and the
      frequent failure to include it in the differential diagnosis of speech problems
      may make the defect's discovery a belated one. This report is a case of
      incomplete submucous cleft palate and its management.

PMID- 23172511
TI  - Bilateral buccal bifurcation cyst.
AB  - This report describes an unusual case of bilateral buccal bifurcation cyst in a 9
      year-old patient, presenting as a slight expansion in the mandibular body region
      in correspondence with the first permanent mandibular molar bilaterally.

PMID- 23172512
TI  - Synchronous central giant cell granuloma and ossifying fibroma of the mandible.
AB  - Central giant cell granuloma (CGCG) is a benign lesion of the jaws. In most
      cases, the lesion presents as a painless, slow-growing swelling of the jaws.
      Ossifying fibroma (OF) of the jaw is a benign neoplasm that consists of variable
      amounts of mineralized material embedded in a fibrous stroma. The simultaneous
      occurrence of CGCG with odontogenic fibroma or OF has been described as combined
      lesions. However, synchronous presentation of CGCG and OF in the mandible is a
      rare occurrence. This report describes a case of 2 completely independent CGCG
      and OF located on both posterior regions of the mandible.

PMID- 23172513
TI  - Merging the computed tomography and magnetic resonance imaging images for the
      visualization of temporomandibular joint disk.
AB  - Computed tomography (CT) depicts intricate bony details well, whereas magnetic
      resonance imaging (MRI) offers excellent contrast to the anatomy of soft tissues.
      This technical report offers a method to merge the CT and MRI images using
      Photoshop software and yield hybrid images that combine the key features of both
      CT and MRI. In this hybrid image, the temporomandibular joint (TMJ) disk was
      clearly displayed, and the relationship between the TMJ disk and surrounding
      skeleton structures, including glenoid fossa and condyle, also was finely
      demonstrated. Although the merging process is not absolutely accurate, the method
      presented in this article can be applied as a supplementary way to help the
      physicians to read the image of TMJ in an even better fashion and also may offer
      a useful method to help the junior physicians to quickly identify the TMJ disk.

PMID- 23172514
TI  - Local delivery of the hemostatic agent tranexamic acid in chronically
      anticoagulated patients.
AB  - In oral surgery, the management of patients on anticoagulant therapy is still
      challenging because of the risks of uncontrolled bleeding and, if the therapy is
      discontinued, the possibility of undesired thromboembolic complications. The use
      of local hemostatic agents may be a viable alternative to overcome these issues.
      Along these lines, the aim of this work was to evaluate the use of newly
      developed swelling matrices loaded with tranexanic acid in preventing
      postextractive bleeding in patients with no modification of oral anticoagulant
      therapy. The matrices are made up of cellulose and are able to fit the
      tridimensional postextractive alveolar cavity, thus assuring also a mechanical
      contribution to homeostasis. The potential of this new therapeutic approach in
      reducing hospitalization, removing the risk of infections, and lowering the
      number of hemorrhagic complications was demonstrated.

PMID- 23172515
TI  - Snake bite envenomation in tongue.
AB  - Snake bite envenomation has considerable medical importance because of its
      frequency and severity. An updated standardization of diagnosis and treatment
      conduct is essential. At no time did the patient develop respiratory
      insufficiency, neurotoxicity, or renal failure. Tongue damage rapidly resolved
      after early and aggressive treatment. The preserved tongue remained well perfused
      and viable, and tongue mobility was good. The aim of the present study was to
      describe a rare case of snake bite envenomation in the tongue, emphasizing risk
      factors, the patient's clinical evolution, and the importance of early,
      multidisciplinary treatment.

PMID- 23172516
TI  - Craniofacial magnetic resonance imaging with a gold solder-filled chain-like wire
      fixed orthodontic retainer.
AB  - Magnetic resonance imaging (MRI) is one of the most powerful tools in diagnostic
      imaging. With the growing rates of orthodontic treatment, there are increasing
      chances of post-orthodontic treatment patients permanently wearing fixed
      retainers who shall undergo MRI examination.Three adolescent patients were
      referred for craniofacial MRI examination. All the patients had completed full
      orthodontic treatment with a retention protocol of permanently wearing bonded
      gold solder-filled wire fixed retainers. In the first 2 cases, the MRI
      examination was performed on a 1.5-T system and in the last case on a 3-T
      system.All the images achieved were of good quality and high resolution. No
      adverse effects were reported by the first 2 patients including no complaint of
      heat sensation or any other discomfort in the anterior teeth area. The third
      patient complained of a headache during the MRI examination.Radiologists and
      technicians may consider allowing performance of MRI examination using 1.5-T
      systems when a gold solder-filled wire fixed retainer is involved with no concern
      regarding the patient's health or the accuracy of the MRI scans.

PMID- 23172517
TI  - Mucocele of the glands of Blandin-Nuhn after lingual frenectomy.
AB  - Mucoceles are the most common lesions of the minor salivary glands and typically
      appear as a fluctuant, bluish, nontender, submucosal swelling with a normal
      overlying mucosa. Mucoceles of the glands of Blandin-Nuhn (in the anterior
      portion of the ventral surface of the tongue) have been considered to be
      uncommon. This article reports an unusual case of a large extravasation mucocele
      involving the ventral surface of the tongue, which appeared after a lingual
      frenectomy.

PMID- 23172518
TI  - The chemotherapy long-term effect on cognitive functions and brain metabolism in
      lymphoma patients.
AB  - AIM: A growing number of neuropsychological studies reported that chemotherapy
      may impair brain functions, inducing persistent cognitive changes in a subset of
      cancer survivors. The aim of this paper was to investigate the neural basis of
      the chemotherapy induced neurobehavioral changes by means of metabolic imaging
      and neuropsychological testing. METHODS: We studied the resting brain [18F]FDG
      PET/CT images of 50 adult cancer patients with diagnosis of lymphoma: 18 patients
      were studied prior and 32 after to chemotherapy. All patients underwent to a
      neuropsychological examination assessing cognitive impairment (tests for shifting
      attention, verbal memory, phonemic fluency), depression, anxiety and distress.
      RESULTS: Compared to no chemotherapy patients, the treated group showed
      significant bilateral lower rate of glucose metabolism in prefrontal cortices,
      cerebellum, medial cortices and limbic brain areas. The metabolism of these
      regions negatively correlated with number of cycles and positively with post
      chemotherapy time. The treated group showed a poorer performance in many frontal
      functions, but similar level of depression, anxiety and distress. CONCLUSIONS:
      Chemotherapy induced significant long-term changes in metabolism of multiple
      regions with a prevailing involvement of the prefrontal cortex. The observed
      cognitive dysfunctions could be explained by these changes. The recovery from
      chemotherapy is probably affected by treatment duration and by the time elapsed
      after its end. We speculated that the mechanism could be an accelerating ageing /
      oxidative stress that, in some patients at risk, could result in an early and
      persistent cognitive impairment.

PMID- 23172519
TI  - [Treatment of super obesity by laparoscopic Roux-en-Y gastric bypass: experience
      of 42 cases].
AB  - OBJECTIVE: To investigate the feasibility and efficacy of laparoscopic Roux-en-Y
      gastric bypass(LRYGB) for super obesity(BMI>=50 kg/m(2)). METHOD: Clinical data
      of 42 patients undergoing LRYGB in the First Affiliated Hospital of Jinan
      University between 2004 and 2008 were analyzed retrospectively. RESULTS: All the
      LRYGB procedures were successfully performed with no conversion to open surgery.
      Average operation time was 145.1 minutes, volume of blood loss during the surgery
      was 25.0 ml, and length of postoperative hospital stay was 9.9 days. The cases
      were followed up for 1 month to 30 months. Body weight and BMI decreased
      significantly 1 month after the operation and reached a minimum level after 2
      years then became stable while excess body weight loss rate(EWL)
      increased(P<0.05). All  the obese-related symptoms were relieved significantly.
      Four cases(9.5%) showed complications during perioperative period including 1
      case of respiratory failure, 2 cases of gastrojejunal anastomotic bleeding, 1
      case of umbilical wound infection,  and  11  developed  long-term  complications.
      All of them were cured by conservative treatment. CONCLUSIONS: Treatment of super
      obesity by LRYGB is feasible with significant short-term results. But due to the
      difficulty of the operation and postoperative complications, comprehensive
      treatment from experienced bariatric surgical team is needed. The long-term
      outcome needs for further observation.

PMID- 23172520
TI  - [Efficacy of laparoscopic gastric bypass on simple obesity patients and analysis
      of influence factors].
AB  - OBJECTIVE: To evaluate the outcomes and factors related to weight loss after
      laparoscopic gastric bypass(LGBP) in obese patients. METHODS: Forty-one obese
      patients who underwent LGBP from May 2010 to December 2011 in the First
      Affiliated Hospital of Nanjing Medical University were followed up. The operative
      time, intraoperative complications, postoperative complications, preoperative
      body mass index(BMI), postoperative BMI, and excess weight loss rate(EWL) were
      determined and their correlation with efficacy were analyzed. RESULTS: All the
      surgeries were successful without conversions or perioperative deaths. The
      average operative time was (229+/-96)min, intraoperative blood loss was(15+/-3)
      ml, postoperative hospital stay was(5.7+/-1.7) d. Patients were followed up for 3
      12 months. The average EWL at 1, 3, 6, 9, and 12 months after operation was
      24.2%, 45.6%, 60.1%, 66.5% and 69.0%. The EWL was negatively correlated with
      preoperative BMI(P<0.01), but not correlated with age, gender, and waist-hip
      ratio(all P>0.05). Postoperative short-term EWL did not differ between central
      obesity patients and peripheral obesity patients, and before and after
      standardized treatment(both P>0.05). After standardization, however, operative
      time and postoperative hospital stay were significantly reduced(P<0.01).
      CONCLUSIONS: LGBP is an effective and feasible treatment for obesity patients.
      Short-term efficacy after surgery is negatively correlated with preoperative BMI.
      Standardization may reduce operative time and postoperative hospital stay, but
      not associated with improved short-term outcomes.

PMID- 23172521
TI  - [Efficacy comparison between 2 methods of laparoscopic gastric bypass surgery in
      the treatment of type 2 diabetes mellitus].
AB  - OBJECTIVE: To investigate the outcomes after 2 methods of laparoscopic gastric
      bypass surgery for patients with type 2 diabetes mellitus(T2DM). METHODS: From
      December 2009 to June 2011, 21 patients with T2DM underwent laparoscopic gastric
      bypass surgery, including laparoscopic Roux-en-Y gastric bypass (LRYGB, n=11),
      and laparoscopic mini-gastric bypass (LMGB, n=10). Clinical data were analyzed
      retrospectively. RESULTS: The clinical complete remission rate of T2DM was
      64%(7/11) in LRYGB group, and 60%(6/10) in LMGB group. The clinical partial
      remission rate of T2DM was 36%(4/11) in LRYGB group, and 40%(4/10) in the LMGB
      group. There was no significant difference between the two groups(both P>0.05).
      The levels of BMI, waist circumference, HOMA-IR and HbA1c within the
      postoperative 6 months were improved in each group (all P<0.05), but there was no
      significant difference between the two groups(all P>0.05). There were no
      conversion or perioperative deaths in both groups. Compared to LMGB, the LRYGB
      group had longer operative time[(147.0+/-35.9) min vs. (110.5+/-39.7) min,
      P=0.038] and postoperative hospital stay [(8.9+/-2.3) d vs. (7.1+/-1.4) d,
      P=0.046). One patient suffered from ileus in LRYGB group, one patient suffered
      from reflux esophagitis and one suffered chronic diarrhea in LMGB group. The
      incidence of postoperative complication was similar between the two
      groups(P>0.05). CONCLUSION: LRYGB and LMGB may result in satisfactory and safe
      effects for the treatment of T2DM, while the LMGB is simpler and associates with
      quicker recovery.

PMID- 23172522
TI  - [Analysis of laparoscopic Roux-en-Y gastric bypass in treating 62 cases of type 2
      diabetes mellitus].
AB  - OBJECTIVE: To evaluate the efficacy of laparoscopic Roux-en-Y gastric bypass
      (LRYGB) in the treatment of type 2 diabetes mellitus(T2DM). METHODS: Clinical
      data of 62 cases undergoing LRYGB from May 2010 to October 2011 were analyzed
      retrospectively. RESULTS: LRYGB was completed in 58 patients successfully. The
      mean operative time was(144.5+/-59.0) min and the mean intraoperative blood loss
      was(57.8+/-135.5) ml. Postoperatively two patients developed anastomotic
      bleeding, one gastric paralysis, one anastomotic leak, and one malnutrition,
      which were all healed by conservation treatment. One patient developed
      anastomotic stricture which was alleviated by balloon dilatation. Forty-nine
      cases were followed up for six months, in whom 34 patients required no further
      medical treatment, 9 received less medicines, and 6 were inactive. Body mass
      index, fasting C-peptide, and HbA1c were improved postoperatively. Compared to
      other patients, the 34 patients with clinical complete remission had higher BMI
      and shorter disease course(both P<0.05). CONCLUSIONS: LRYGB can safely and
      efficiently be applied in T2DM patients. Short-term efficacy is satisfactory and
      the long-term outcomes require further evaluation.

PMID- 23172523
TI  - [Efficacy evaluation of laparoscopic gastric bypass for the treatment of obese
      type 2 diabetes mellitus].
AB  - OBJECTIVE: To explore the treatment outcomes of obese type 2 diabetes mellitus
      (T2DM) after laparoscopic gastric bypass. METHODS: The clinical data of 18
      patients with obese T2DM who underwent laparoscopic Roux-en-Y gastric bypass in
      Beijing Shijitan Hospital between March 2009 and February 2011 were
      retrospectively analyzed. The clinical parameters included preoperative and
      postoperative blood glucose, blood lipid, nutrition status and weight lose.
      RESULTS: Eighteen patients included 8 men and 10 women. The range of age was 27
      62 years (mean, 42.4+/-10.7 years). The range of BMI was 28.7-57.4 kg/m(2)(mean,
      34.9+/-6.9 kg/m(2)). All the patients underwent laparoscopic Roux-en-Y gastric
      bypass, and no mortality, complication or conversion to open operation occurred.
      At 3 months after operation, there were significant changes in OGTT, BMI, HbA1c,
      Homa-IR and Homa-beta(all P<0.05). Fourteen patients(77.8%) showed clinical
      complete remission, and the overall effective rate was 100%(18/18). The level of
      blood lipid decreased significantly (P<0.05), and the change of nutritional
      status was not statistically significant(P>0.05). CONCLUSION: Gastric bypass is
      an effective treatment for obese type 2 diabetes mellitus.

PMID- 23172524
TI  - [Effect of Roux-en-Y gastric bypass on quality of life in non-obese patients with
      type 2 diabetes mellitus].
AB  - OBJECTIVE: To observe the impact of Roux-en-Y gastric bypass on quality of life
      in non-obese patients with type 2 diabetes mellitus. METHODS: Thirty-seven non
      obese patients with type 2 diabetes mellitus who underwent Roux-en-Y gastric
      bypass were prospectively studied. A 36-item short form healthy survey
      questionnaire(SF36), the diabetes treatment satisfaction questionnaire(DTSQ), and
      quality of life scale for patients with type 2 diabetes mellitus(DMQLS) were used
      to evaluate the quality of life for all the non-obese patients with type 2
      diabetes mellitus preoperatively and 12 months postoperatively. RESULT: The blood
      glucose and lipid indexes were significantly decreased after operation(all
      P<0.05). SF36 showed the physical and mental synthesis scores at 12 month after
      operation were 74.6+/-18.3 and 79.8+/-14.9 respectively, higher than those at one
      week before operation(54.9+/-15.1 and 56.4+/-17.8, both P<0.01). DTSQ showed
      treatment satisfaction score was increaced significantly after operation(29.2+/
      7.1 vs. 15.4+/-5.6, P<0.01). The quality of life evaluated by DMQLS, was also
      significantly improved(P<0.01). CONCLUSION: Roux-en-Y gastric bypass can
      significantly improve the quality of life for non-obese patients with type 2
      diabetes mellitus.

PMID- 23172525
TI  - [Efficacy analysis of laparoscopic sleeve gastrectomy in the treatment of obesity
      related comorbidities].
AB  - OBJECTIVE: To investigate the safety and efficacy of laparoscopic sleeve
      gastrectomy (LSG) for the treatment of obesity and related diseases. METHODS:
      Clinical data of 67 patients who underwent LSG between December 2006 and July
      2011 were analyzed retrospectively. Improvements in body mass index(BMI),
      percentage of excess weight loss(EWL), type 2 diabetes mellitus, hypertension and
      other comorbidities were observed at one year postoperatively. RESULTS:
      Laparoscopic procedures were completed in 67 patients without conversion. The
      operative time was(78+/-17) min. The postoperative hospital stay was(5.0+/-1.7)
      d. The postoperative recovery was uneventful and there were no perioperative
      death or severe postoperative complication. Sixty-four patients(95.5%) had a
      postoperative follow up of 1 year. One year after LSG, BMI decreased by(10.4+/
      3.7) kg/m(2) from (37.7+/-4.1) kg/m(2) preoperatively and EWL was(80.2+/-27.7)%.
      In 13 cases of type 2 diabetes mellitus, 7 patients (53.8%, 7/13) were weaned off
      hypoglycemic agents or insulin. In 11 cases of hypertension, 5 required no
      medications(45.5%, 5/11). The remission rate was both 100%. There was significant
      resolution or improvement of other obesity-related comorbidiities, including
      hyper-triglyceridemia(n=51), hyperuricemia(n=42), sleep apnea syndrome (n=2),
      osteoarticular disease (n=9), and acanthosis (n=8). CONCLUSIONS: LSG is safe and
      feasible for the treatment of obesity and can cure or improve type 2 diabetes
      mellitus, hypertension and other obesity related comorbidities.

PMID- 23172526
TI  - [Influence of gastric bypass surgery on hepatic gluconeogenesis in type 2
      diabetic Goto Kakizaki rats].
AB  - OBJECTIVE: To investigate the influence and significance of gastric bypass
      surgery on hepatic gluconeogenesis in type 2 diabetic Goto Kakizaki(GK) rats.
      METHODS: Forty GK rats were randomly divided into Roux-en-Y gastric bypass
      group(group A) and sham operation group(group B). Differences in glucose
      tolerance experiment(OGTT) at preoperative and postoperative 1, 2 and 4 weeks
      were compared and weight was recorded. Glycated hemoglobin levels were measured
      preoperatively and 4 weeks postoperatively. The animals were sacrificed 4 weeks
      after surgery and liver tissues were harvested to detect the relative expression
      of mRNA and protein of glucose 6 phosphatase(G-6-P) and phosphoenol pyruvate
      kinase(PEPCK) with RT-PCR and Western blot. RESULTS: Fasting blood glucose levels
      were 6.5, 4.9, and 4.7 mmol/L in group A, and were 10.3, 10.4, and 12.5 mmol/L in
      group B, and the differences between two groups were statistically
      significant(P<0.05). The blood glucose level at 2 h after stomach lavage were
      8.3, 6.4 and 5.5 mmol/L in group A, and were 21.4, 23.8 and 24.7 mmol/L in group
      B at postoperative 1, 2, 4 weeks, and the differences between two groups were
      statistically significant(P<0.05). The glycosylated hemoglobin at postoperative 4
      weeks was(6.8+/-1.0)%, significantly lower than that in group B[(7.9+/-0.8)%,
      P<0.05]. Hepatic G-6-P and PEPCK mRNA relative expression at postoperative 4
      weeks was reduced by 21.0% and 25.9% respectively as compared to group B, and the
      protein expression reduced as well. Immunohistochemistry showed that hepatic
      glycogen sedimentary in group A increased significantly. CONCLUSION: The relative
      mRNA and protein level of key enzymes of hepatic gluconeogenesis are
      significantly decreased after Roux-en-Y gastric bypass surgery and hepatic
      gluconeogenesis is reduced, which may be a potential mechanism of the decrease of
      blood glucose.

PMID- 23172528
TI  - [Meta-analysis of efficacy and safety on neoadjuvant therapy for rectal cancer].
AB  - OBJECTIVE: To assess the value of neoadjuvant therapy for resectable rectal
      cancer and the impact on postoperative complications. METHODS: Literature search
      was performed in PubMed, Ovid, Web of Science, Springer-Link and Elsevier
      ScienceDirect for randomized controlled trials published before May 2010 that
      compared neoadjuvant therapy with surgery alone or postoperative adjuvant
      therapy. The computer search was supplemented with hand search of reference lists
      for available primary studies. Inclusion criteria and quality assessment were
      performed. RESULTS: Eleven studies including 7407 patients were enrolled for
      analysis. Neoadjuvant therapy group had significant advantages in local
      recurrence (OR=0.43, 95%CI:0.37-0.50, P<0.01), distant recurrence (OR=0.85,
      95%CI:0.76-0.95, P<0.01), 5-year overall survival (RR=1.15, 95%CI:1.04-1.28,
      P<0.01), and sphincter-saving surgery (RR=1.48, 95%CI:1.17-1.87, P<0.01). There
      were no significant difference in postoperative mortality rate(OR=1.20,
      95%CI:0.68-2.13, P=0.53) and anastomotic complications (OR=1.04, 95%CI:0.73-1.48,
      P=0.84). CONCLUSION: Neoadjuvant therapy improves local control, distant
      recurrence and long-term survival without increasing postoperative complications.

PMID- 23172527
TI  - [Effect of gastric bypass surgery on mRNA expression level of hepatic
      phosphoenolpyruvate carboxykinase in type 2 diabetic Goto-Kakizaki rats].
AB  - OBJECTIVE: To investigate the effects of gastric bypass surgery(GBP) on hepatic
      phosphoenolpyruvate carboxykinase(PEPCK) mRNA expression in type 2 diabetic Goto
      Kakizaki rats. METHODS: Male GK rats were randomized into three groups: gastric
      bypass surgery(n=10), sham operation with diet restriction(n=10), and sham
      operation alone(n=10). Liver specimens of GK rats were collected during the
      intraoperative period for self-control study and 8 weeks after surgery. Fasting
      blood glucose, food intake, and body weight were recorded before surgery and 1,
      2, 4, 8 weeks after surgery. The expression of PEPCK mRNA was measured by real
      time PCR. RESULTS: The fasting plasma glucose level decreased from(17.6+/-2.1)
      mmol/L before surgery to(7.5+/-0.9) mmol/L 8 weeks after surgery in GBP group.
      The level of PEPCK mRNA decreased from 1.08+/-0.38 before surgery to 0.41+/-0.10
      8 weeks after surgery, significantly lower than that in sham operation alone
      group(1.04+/-0.12)(P<0.01). The level of PEPCK mRNA in diet restriction group
      increased from 1.15+/-0.16 before surgery to 2.54+/-0.82 8 weeks after
      surgery(P<0.01). The expression of PEPCK mRNA in diet restriction was
      significantly higher than that in CBP group(P<0.01). CONCLUSIONS: GBP can
      significantly improve hyperglycemia in type 2 diabetic GK rat models, which may
      be associated with the decrease of hepatic PEPCK mRNA level.

PMID- 23172529
TI  - [Study on relationship of the K-ras mutation with the occurrence of colorectal
      liver metastasis and survival outcomes].
AB  - OBJECTIVE: To analyze the relationship of K-ras mutation with the development of
      liver metastasis in colorectal cancer patients and the survival outcomes.
      METHODS: From 2003 to 2008, 300 patients who underwent colorectal cancer surgery
      in the Department of General Surgery of Zhongshan Hospital, Fudan University were
      assigned to different groups, according to the diagnosis and follow-up results.
      The mutation of exon 2 of K-ras was detected in primary paraffin-embedded lesions
      by PCR and Pyrosequencing. The association of gene mutation with the development
      of liver metastasis and its prognosis was studied. RESULTS: Among 300 cases, the
      mutations of exon 2 were present in 120 cases(40%). The G13D mutation was more
      common in metachronous metastasis group than that in synchronous group(17.0% vs.
      8.0%, P=0.041). Multivariable regression analysis showed that G13D mutation was
      an independent risk factor(HR=1.108, 95%CI:1.032-5.062, P=0.048) for metachronous
      metastasis. Patients with mutated K-ras had a poorer overall survival compared to
      those without mutated K-ras for patients without liver metastasis(median overall,
      65 vs. 72 months, P=0.039), and for patients who received metastasis
      resection(median disease-free survival 18 vs. 24 months, P=0.048). Multivariable
      analysis showed that K-ras mutation was an independent risk factors of overall
      survival(HR=1.561, 95%CI:1.022-6.422, P=0.045) in patients without liver
      metastasis. CONCLUSION: Detection of K-ras mutation may predict the development
      of liver metastasis and prognosis.

PMID- 23172530
TI  - [Expression of hMLH1 in rectal intraepithelial neoplasm and early rectal
      carcinoma].
AB  - OBJECTIVE: To explore whether the abnormality of hMLH1 gene may be an early event
      of carcinogenesis in rectal carcinoma, and to evaluate the diagnostic value in
      differentiation between intraepithelial neoplasm and early stage of colorectal
      carcinoma. METHODS: The expression of hMLH1 protein in 28 cases with early
      invasive rectal carcinoma(EIRC), 36 cases with rectal intraepithelial
      neoplasm(RIEN), and 30 cases with normal rectal mucosa(NRM) which were collected
      through surgical operations were detected by PV-9000 immunohistochemical method.
      RESULTS: The positive expression rates of hMLH1 protein were 100%(30/30),
      77.8%(28/36), and 39.3%(11/28) in NRM, RIEN, and EIRC respectively. The
      difference was statistically significant between RIEN and EIRC(P=0.002), and the
      difference was also statistically significant between RIEN and NRM(P=0.006). The
      positive expression of hMLH1 was not related to age, gender, tumor maximum
      diameter, dysplasia, tumor types, and distance from the anal verge in RIEV
      group(P>0.05). In EIRC group, hMLH1 was associated with tumor
      differentiation(P<0.05). CONCLUSION: hMLH1 gene deletion may be an early event
      during carcinogenesis of rectal carcinoma, which may be useful in differentiation
      of intraepithelial neoplasm from early rectal carcinoma.

PMID- 23172531
TI  - [Expression of connective tissue growth factor in colorectal cancer and its
      association with prognosis].
AB  - OBJECTIVE: To investigate the expression of connective tissue growth factor
      (CTGF) in colorectal cancer(CRC) and its association with clinicopathologic
      parameters and overall survival rate. METHODS: Fresh tumor tissues and matched
      distal normal colon tissues were collected from 92 patients diagnosed as CRC by
      surgical operation. The expression level of CTGF mRNA was quantified by
      quantitative reverse transcription PCR. Thirty out of 92 pairs of tissue
      specimens were selected randomly to detect CTGF protein by immunohistochemistry.
      All the cases were followed up to identify prognostic factors for survival.
      RESULTS: CTGF mRNA expression was up-regulated in CRC. The positive rate of CTGF
      protein expression tissues (73.3%) was significantly higher than that in the
      corresponding normal tissues (23.3%, P<0.01). CTGF expression was lower in
      patients with lymphatic metastasis or stage III/IIII disease (all P<0.05). A
      negative association was also observed between the CTGF protein positive rate and
      tumor infiltration depth (P<0.05). The relative expression of CTGF mRNA in tumor
      tissues was classified into high and low expression groups. The 5-year cumulative
      survival rate was lower in patients with low CTGF expression (29.3%) as compared
      to those with high CTGF expressions (68.3%) (P<0.01). Cox regression analysis
      revealed that the relative expression level of CTGF was independent factor of
      overall survival (RR=2.960, 95%CI:1.491-1.587, P<0.01). ROC curve analysis showed
      that sensitivity and specificity of CTGF mRNA expression for prediction of 5-year
      survival were 64.9% and 74.5%, respectively. CONCLUSIONS: The aberrant expression
      of CTGF is associated with the malignant biological behaviors of CRC. Low
      expression of CTGF is associated with worse prognosis of CRC.

PMID- 23172532
TI  - [Predicting value of dynamic alteration of blood neutrophil/lymphocyte ratio on
      recurrence-free  survival in patients with advanced colon cancer after operation
      and chemotherapy].
AB  - OBJECTIVE: To evaluate whether neutrophil-lymphocyte ratio(NLR) predicts risk of
      recurrence in patients with advanced colon cancer undergoing curative resection
      followed by adjuvant chemotherapy. METHODS: A total of 149 patients with advanced
      colon cancer undergoing curative resection followed by adjuvant
      chemotherapy(FOLFOX6 protocol) were included. NLR was calculated preoperatively
      and before chemotherapy. The changes in NLR and the predictive value of NLR for
      prognosis were analyzed. RESULTS: The NLR of 149 patients was 2.8+/-1.5. NLR of
      3.5 was identified according to the ROC curve. NLR<3.5 and NLR>=3.5 were
      classified as low and high NLR group, respectively. The 5-year recurrence-free
      survival(RFS) of patients with high preoperative NLR(n=22) was significantly
      worse than that of those with low preoperative NLR(n=127)(50.9% vs. 76.4%,
      P=0.025). The difference of 5-year RFS between high pre-chemotherapy NLR
      group(n=34) and low pre-chemotherapy NLR group(n=115) was statistically
      significant(50.1% vs. 71.4%, P=0.032). The 5-year RFS was 79.5% in patients with
      low preoperative NLR converting to high pre-chemotherapy NLR(n=16), similar to
      the group with high pre-chemotherapy group(P=0.077). The 5-year RFS was 17.7% in
      patients with high preoperative NLR reverting to low pre-chemotherapy NLR(n=12),
      similar to the group with low pre-chemotherapy group(P=0.978). There was
      significant difference in 5-year RFS between the postoperatively elevated group
      and postoperatively decreased group(P=0.036). CONCLUSION: An elevated blood NLR
      may be a biomarker of poor RFS in patients with advanced colon cancer after
      curative resection and chemotherapy.

PMID- 23172533
TI  - [Endoscopic submucosal enucleation for gastric submucosal tumors originated from
      muscularis propria layer: clinical analysis of 116 case].
AB  - OBJECTIVE: To explore the efficacy and safety of endoscopic submucosal
      enucleation (ESE) for gastric submucosal tumors (SMTs) originated from muscularis
      propria. METHODS: A total of 116 patients with gastric SMT originated from
      muscularis propria underwent ESE in Department of Gastroenterology of the Taizhou
      Hospital between July 2006 and March 2011. The occurrence of intra-operative and
      post-operative complications and corresponding treatment were recorded. After the
      treatment of ESE, the patients were followed up endoscopically. RESULTS: The
      success rate of operation was 96.6%. The mean time of the procedure was (51.9+/
      16.3) min. Complications included intra-operative bleeding (n=9, 7.8%),
      perforation (n=20, 17.2%), and post-operative bleeding (n=3, 2.6%). Among them, 5
      cases (4.3%) required surgical intervention. None of patient had other
      complications such as peritoneal abscess or peritonitis. The mean hospitalization
      time after ESE was 6.1 days. The median follow-up period was 12 months (range, 3
      48 months) and there was no residual tumor or recurrence. CONCLUSION: ESE is a
      safe and feasible treatment for patients with gastric SMT originated from
      muscularis propria.

PMID- 23172534
TI  - [Study of inhibiting and killing effects of transgenic LIGHT human umbilical cord
      blood mesenchymal stem cells on stomach cancer].
AB  - OBJECTIVE: To study the inhibition and killing effect of transgenic LIGHT
      umbilical cord blood mesenchymal stem cells (UCBMSCs) on stomach carcinoma.
      METHODS: The LIGHT gene was recombined to construct the transfer plasmid pGC-FU
      LIGHT by infusion technique. The 293T cells were co-transfected with the transfer
      plasmid pGC-FU-LIGHT, the construction plasmid Helper 1.0 and the envelope
      plasmid Helper 2.0 with the help of lipofectamine 2000 to produce lentiviral
      particles. Transgenic UCBMSCs(MSC-LIGHT) and empty carrier UCBMSCs (MSC) were
      obtained. Human gastric cancer cell SGC-7901 was injected into nude mice
      subcutaneously groin. The model of transplanted human gastric cancer cell SGC
      7901 in nude mice was established. Tumorigenesis nude mice were separated into
      three groups randomly with 5 in each group: MSC-LIGHT group, MSC group, and NS
      group. Three groups of nude mice were injected around the tumor with MSC-LIGHT,
      MSC and NS every other day for 3 times. Four weeks later, the transplanted
      gastric cancer volume was measured. The expressions of LIGHT in the three groups
      were determined by RT-PCR and ELISA method. The necrosis area in the tumors was
      calculated under pathological examination. RESULTS: The average volume of
      transplanted tumor was(0.45+/-0.25) cm(3) in MSG-LIGHT group, (0.64+/-0.36) cm(3)
      in MSG group, and(1.21+/-0.79) cm(3) in NS group, and the difference was
      statistically significant(P<0.05). The LIGHT mRNA was 2.96+/-0.27, 1.23+/-0.47,
      and 0.73+/-0.10 respectively. The LIGHT protein was(167.89+/-2.31), (73.22+/
      5.74), and (49.66+/-5.25) ng/L. The differences were all statistically
      significant among the three groups(both P<0.01). Pathological examination showed
      that the necrosis area was largest in MSC-LIGHT group. CONCLUSION: Transgenic
      UCBMSCs secret LIGHT in a paracrine manner, which has inhibition and killing
      effects on stomach carcinoma.

PMID- 23172535
TI  - [Effect of lentivirus-mediated NOB1 gene silencing by RNA interference on
      proliferation and apoptosis of human colon cancer cells].
AB  - OBJECTIVE: To investigate the effect of NOB1 gene on proliferation and apoptosis
      of human colon cancer cell line RKO by RNA interference. METHODS: Small
      interference RNA(siRNA) targeting NOB1 gene was cloned into lentivirus vector.
      Then the lentivirus particles expressing NOB1 short harpin RNA(shRNA) were
      infected into RKO cells. Real-time PCR and Western blot were performed to examine
      the expression of NOB1 in lentivirus infected cells. The Thermo Scientific
      Cellomics ArrayScan VTI HCS Reader was used to test the proliferation and colony
      formation of RKO cells, and flow cytometry assay was performed to detect cell
      cycle and apoptosis. Xenograft tumor was established by injection of RKO cells
      into nude mice, then NOB1-shRNA was injected into the tumor and tumor volume was
      detected. RESULTS: Compared to negative controls, the expression levels of NOB1
      mRNA and protein were both significantly down-regulated, the proliferation and
      colony-forming capacity of RKO cells were significantly inhibited, and cell
      apoptosis was increased after 3 days of NOB1-shRNA lentivirus infection(all
      P<0.05). The tumor volume was significantly smaller in NOB1-shRNA group than that
      in Scr-shRNA group[(405+/-102) mm(3) vs.(870+/-165) mm(3), P<0.05]. CONCLUSION:
      Silencing NOB1 gene by RNA interference may provide an inhibitive effect on human
      colon cancer development.

PMID- 23172536
TI  - [Effects of RNA interference and nolatrexed on thymidylate synthase expression
      and cell proliferation of human colorectal carcinoma LOVO cells].
AB  - OBJECTIVE: To investigate the effect of the RNAi and the chemotherapy drugs
      nolatrxed on the expression of thymidylate synthase(TS) and the growth of the
      colorectal carcinoma LOVO cells. METHODS: The siRNA was constructed targeting the
      human TS gene, and then transfected into the human colorectal cancer LOVO cells.
      RT-PCR and Western blot technique were used to observe the TS gene and protein
      expression levels, and MTT was used to detect cell proliferation after silencing
      the TS gene. In addition, siRNA and nolatrxed were applied to the LOVO cells to
      observe the TS protein expression and cell growth. RESULTS: TS siRNA
      significantly reduced the expression of TS gene and protein in LOVO cells, and
      inhibited cell growth. The IC50 value of LOVO cells was (1.46+/-0.25) MUmol/L in
      TS siRNA combined with nolatrexed group, (6.81+/-0.31) MUmol/L in the negative
      control group, and (6.47+/-0.43) MUmol/L in the single nolatrexed group. After
      treatment of TS siRNA combined with nolatrexed on LOVO cells for 36 hours, the
      apoptosis index was higher than that in single TS siRNA and nolatrexed[(62.12+/
      0.89)% vs.(21.56+/-0.67)% and(40.51+/-0.83)%, both P<0.05]. CONCLUSION: TS siRNA
      can partly suppress the expression of TS gene in LOVO cells, inhibit cell
      proliferation, promote cell apoptosis and enhance cell sensitivity to apoptosis
      induced by nolatrexd.

PMID- 23172537
TI  - [Growth hormone secretagogue participates in two-way regulation of the motility
      of small intestinal smooth muscle in rats].
AB  - OBJECTIVE: To investigate the effect of growth hormone secretagogue(ghrelin) on
      the contraction and relaxation of small intestinal smooth muscle in rats and its
      mechanism. METHODS: Twenty-four vagotomized rats were injected intraperitoneally
      with different concentrations of ghrelin (0, 20, 40, 80 MUg/kg). The small
      intestinal transit were observed. The effect of ghrelin(0.01, 0.1, 0.5, 1.0
      MUmol/L) on the contraction and relaxation of rat small intestinal smooth muscle
      strips was observed in vitro in the presence of carbachol(50 nmol/L), the
      locations of ghrelin receptors(GHS-R1a) on different cells in small intestinal
      muscle layers were detected by immunofluorescence. RESULTS: With the increase of
      concentrations, ghrelin elevated the percentage of small intestinal
      transit[(25.4+/-1.0)%, (33.7+/-1.9)%, (39.3+/-2.4)%, (44.7+/-2.1)%] in a dose
      dependent manner, and the differences were statistically significant among
      groups(P<0.05). Ghrelin could also enhance the contraction [(67.0+/
      2.4)%,(149.5+/-3.3)%, (187.1+/-4.7)%, (213.5+/-3.4)%] and relaxation[(35.3+/
      1.1)%, (62.9+/-3.8)%, (79.6+/-2.7)%, (94.6+/-2.2)%] of smooth muscle strips
      mediated by Cch in a dose-dependent manner, and the differences were
      statistically significant among groups(P<0.05). Immunofluorescence revealed that
      ghrelin receptors mainly located on membrane of the nerve cells in the muscle
      layers, while no receptors were observed on membrane of the smooth muscle cells.
      CONCLUSION: Ghrelin may enhance the effect of the contraction and relaxation of
      the rat small intestinal smooth muscle mediated by cholinergic neurotransmitters
      by activating the nerve cells in the enteric plexus.

PMID- 23172538
TI  - High affinity sulfate binding in aqueous media by cyclic peptides with thiourea
      arms.
AB  - Tripodal thioureas based on a cyclic peptide scaffold have been synthesised and
      their anion binding properties evaluated. These receptors show high affinity
      towards sulfate ions in aqueous solution.

PMID- 23172539
TI  - Assessment and profiling of the fatty acids in two ackee fruit (Blighia sapida
      Koenig) varieties during different ripening stages.
AB  - BACKGROUND: The ripening of fruits is characterized by physical, chemical and
      biochemical compositional changes such as color, sugars and phenolic compounds.
      Ackee fruit is famous in Jamaica and the Caribbean. This study aimed to assess
      the variation of fatty acids in two varieties (cheese and butter) ackee (Blighia
      sapida) fruits during five different ripening stages. RESULTS: The total fatty
      acid content of ackee fruit was much higher in arils and ranged from 283.4 to
      465.1 g kg(-1) dry weight (DW), while in husk they ranged from 235.2 to 465.1 g
      kg(-1) DW in both varieties. Total fatty acid content declined in the arils and
      the husks as the fruit ripened. Five major fatty acids were found: palmitic acid
      (C16:0) and stearic acid (C18:0), oleic acid (C18:1), linoleic acid (C18:2) and
      linolenic acid (C18:3). In the arils, oleic acid was found at the highest
      concentration, followed by palmitic, stearic, linoleic and last linolenic acid.
      The unsaturated:saturated ratio of fatty acids varied from 1.23 to 3.26 in the
      arils of both varieties, and from 1.03 to 5.05 in the husk.
      Monounsaturated:polyunsaturated fatty acids ranged from 8.56 to 25.19 in the
      arils and from 0.62 to 2.33 in the husk. CONCLUSION: The results show that ackee
      arils contain much higher levels of fats than the husk and the major fatty acid
      in the arils was oleic acid (Delta9-cis-oleic acid, an omega n-9), while in the
      husk unsaturated fatty acids were higher than the saturated ones. Oleic acid was
      the major fatty acid in both varieties, and aril fatty acid content was 10-20
      times higher than in the husk. In both varieties, unsaturated fatty acids were
      relatively higher than saturated ones; however, total fatty acids showed a
      decline with ripening for arils and husk tissues.

PMID- 23172540
TI  - The bihemispheric posterior interior cerebellar artery: anatomic variations and
      clinical relevance in 11 cases.
AB  - PURPOSE: Although the anatomic course of the posterior interior cerebellar artery
      (PICA) is variable, it is thought to be very rare for the artery to cross
      midline, with an estimated incidence of 0.1%. Bihemispheric PICA crosses midline
      and typically serves both PICA territories. METHODS: We present 11 cases of
      bihemispheric PICA discovered from retrospective angiogram review, the largest to
      date reported in the literature. RESULTS: Five cases were the typical
      bihemispheric PICA pattern, three were bihemispheric with distal vertebral
      hypoplasia, two cases were the vermian type, and one was atypical, with the PICA
      feeding a contralateral cerebellar arteriovenous malformation (AVM). The
      branching point to the contralateral hemisphere always occurred distal to the
      ascending tonsillar loop and all true bihemispheric variants had contralateral
      PICA aplasia. CONCLUSIONS: The true incidence of this variant may be much higher
      than previously thought (3.6% in the current series), and has relevance for
      cerebrovascular disease, including aneurysm, AVM, and ischemic stroke.
      Neuroradiologists, neurologists, and neurosurgeons should be aware of this
      potential variant.

PMID- 23172541
TI  - Combined balloon stent technique with the Scepter C balloon and low-profile
      visualized intraluminal stent for the treatment of intracranial aneurysms.
AB  - BACKGROUND: The 'balloon-then-stent' method involves stent placement after
      completion of a balloon-assisted embolization. The drawback to this technique is
      that the coil mass achieved during balloon remodeling must be crossed prior to
      stent deployment. This additional maneuver introduces the potential risk of coil
      disruption. We describe the first report of a novel technique employing the
      'balloon-then-stent' method. METHODS: A 51-year-old patient with an unruptured
      right middle cerebral artery bifurcation aneurysm was treated with balloon
      remodeling employing a 4 * 10 mm Scepter C balloon catheter. Following coil
      embolization, a low-profile visualized intraluminal stent (LVIS) Jr 2.5 mm * 16
      mm was delivered via the coaxial balloon catheter and deployed across the
      aneurysm neck. RESULTS: Follow-up angiograms demonstrated that the coil mass was
      well-seated within the aneurysm sac and the parent vessel was widely patent with
      satisfactory vessel wall apposition by the stent. CONCLUSIONS: We describe a
      technique for balloon remodeling followed by stenting for aneurysm coil
      embolization that incorporates the use of a coaxial dual-lumen balloon catheter
      system through which a novel self-expanding stent can be deployed. In the case
      described, we found this technique to be safe and feasible, reducing both the
      number of steps involved in this technique and the opportunities for mechanical
      coil-related complications.

PMID- 23172542
TI  - Hybrid printing of mechanically and biologically improved constructs for
      cartilage tissue engineering applications.
AB  - Bioprinting is an emerging technique used to fabricate viable, 3D tissue
      constructs through the precise deposition of cells and hydrogels in a layer-by
      layer fashion. Despite the ability to mimic the native properties of tissue,
      printed 3D constructs that are composed of naturally-derived biomaterials still
      lack structural integrity and adequate mechanical properties for use in vivo,
      thus limiting their development for use in load-bearing tissue engineering
      applications, such as cartilage. Fabrication of viable constructs using a novel
      multi-head deposition system provides the ability to combine synthetic polymers,
      which have higher mechanical strength than natural materials, with the favorable
      environment for cell growth provided by traditional naturally-derived hydrogels.
      However, the complexity and high cost associated with constructing the required
      robotic system hamper the widespread application of this approach. Moreover, the
      scaffolds fabricated by these robotic systems often lack flexibility, which
      further restrict their applications. To address these limitations, advanced
      fabrication techniques are necessary to generate complex constructs with
      controlled architectures and adequate mechanical properties. In this study, we
      describe the construction of a hybrid inkjet printing/electrospinning system that
      can be used to fabricate viable tissues for cartilage tissue engineering
      applications. Electrospinning of polycaprolactone fibers was alternated with
      inkjet printing of rabbit elastic chondrocytes suspended in a fibrin-collagen
      hydrogel in order to fabricate a five-layer tissue construct of 1 mm thickness.
      The chondrocytes survived within the printed hybrid construct with more than 80%
      viability one week after printing. In addition, the cells proliferated and
      maintained their basic biological properties within the printed layered
      constructs. Furthermore, the fabricated constructs formed cartilage-like tissues
      both in vitro and in vivo as evidenced by the deposition of type II collagen and
      glycosaminoglycans. Moreover, the printed hybrid scaffolds demonstrated enhanced
      mechanical properties compared to printed alginate or fibrin-collagen gels alone.
      This study demonstrates the feasibility of constructing a hybrid inkjet printing
      system using off-the-shelf components to produce cartilage constructs with
      improved biological and mechanical properties.

PMID- 23172546
TI  - Determination of electrokinetic and hydrodynamic parameters of proteins by
      modeling their electrophoretic mobilities through the electrically charged
      spherical porous particle.
AB  - This work explores the possibility of using the electrically charged "spherical
      porous particle" (SPP) to model the electrophoretic mobility of proteins in the
      low charge regime. In this regard, the electrophoretic mobility expression of the
      charged SPP (Hermans-Fujita model) is used and applied here to BSA and
      staphylococcal nuclease for different protocol pH values. The SPP is presented
      within the general framework of the "spherical soft particle" as described in the
      literature. The physicochemical conditions required to model proteins as SPP from
      their experimentally determined electrophoretic mobilities are established. It is
      shown that particle permeability and porosity and chain packing and friction
      fractal dimensions are relevant structural properties of proteins when
      hydrodynamic interaction between amino acid residues is present. The charge
      regulation phenomenon of BSA and staphylococcal nuclease with pIs ~ 5.71 and
      9.63, respectively, is described through the SPP within a wide range of bulk pH
      values. These case studies illustrate when the average regulating {pH} of the
      protein domain is lower and higher than the protocol pH. Further research for
      using the general spherical soft particle is also proposed on the basis of
      results and main conclusions.

PMID- 23172547
TI  - A combined experimental and computational study on the adsorption and reactions
      of NO on rutile TiO2.
AB  - In this work we combined computational density functional theory with
      experimental infrared spectroscopy to determine the adsorbate structure of NO and
      its reaction products N(2)O(2), N(2)O, and NO(2) on rutile TiO(2). These
      reactions are important for the photo-catalytic reduction of NO in exhaust gas,
      but yet little is known about the mechanisms or the intermediates involved. The
      combination of high-quality ultrahigh vacuum FTIRS data with large scale embedded
      cluster calculations using an accurate hybrid density functional rendered it
      possible to identify and assign unambiguously vibrational frequencies for nine
      species which are formed upon adsorption and reaction of NO on rutile TiO(2).
      Some of them have been observed for the first time. As a result of the quantum
      chemical calculations we can report for all adsorbates accurate structures and
      binding energies.

PMID- 23172548
TI  - A nomogram for perioperative prognostic risk-assessment in twin-twin transfusion
      syndrome.
AB  - OBJECTIVE: Prognostic assessment in twin-to-twin transfusion syndrome (TTTS) is
      ill-defined. The objective of this study is to define a perioperative prognostic
      score for TTTS treated by percutaneous laser coagulation. METHODS: Consecutive
      cases of TTTS treated by percutaneous fetoscopic laser coagulation over a 6-year
      period were reviewed. Twin survival at 28 days was considered using a 3-level
      polytomous variable defined by 0, 1, or 2 fatal events. A multivariate prognostic
      analysis with internal validation was conducted using gestational age at
      diagnosis, weight discordance, umbilical artery, and ductus venosus abnormalities
      in the donor and the recipient respectively, cervical length, selectivity of
      surgery, and transplacental approach. RESULTS: On the basis of 507 cases, the
      perinatal survival rate of 2 and 1 twin was 46.2% and 31.5%, respectively.
      Statistically significant factors included umbilical artery abnormalities in the
      donor, gestational age, and transplacental approach, but with different effects
      regarding survival of 0, 1, or 2 twins. A scoring chart was subsequently
      constructed together with a nomogram for both a preoperative and immediate post
      operative prognostic assessment. CONCLUSION: Part of the prognosis can be
      anticipated by perioperative findings. Although further validation is required,
      the presented nomogram should help unify the prognostic assessment in TTTS.

PMID- 23172549
TI  - Rapid capillary electrochromatographic profiling of phytohormones on a
      hydrophilic interaction/strong anion-exchange mixed-mode monolith.
AB  - An improved hydrophilic interaction/strong anion-exchange (HI-SAX) monolith for
      rapid capillary electrochromatographic profiling has been developed to detect
      carboxylic phytohormones with high resolution. The HI-SAX monolith was prepared
      by copolymerization of 2-(methacryloyloxy)ethyltrimethylammonium methyl sulfate,
      pentaerythritol triacrylate and porogenic solvents. Detailed polymerization
      compositions were investigated and improved, and the characteristics in terms of
      morphology, retention mechanism and column reproducibility were studied. A
      typical hydrophilic chromatography mechanism was observed when ACN content
      exceeded 30%, and the HI-SAX mixed-mode was verified with nucleic acid bases and
      nucleosides. Based on the improved HI-SAX monolith, capillary
      electrochromatographic profiling of typical phytohormones was evaluated by using
      indole-3-acetic acid (IAA), abscisic acid (ABA) and gibberellic acid (GA(3)) as
      the mode analytes. Effects of the test parameters on carboxyl phytohormones were
      investigated, and a fast analysis with high resolution for the representative
      phytohormones was achieved within 4.0 min with intraday RSDs (n = 3) less than
      2.6% and 6.3% for the retention time and peak area, respectively. When applied to
      spiked corn samples, mean recoveries between 82.3% and 95.4% were obtained.

PMID- 23172550
TI  - The influence of counter ion and ligand methyl substitution on the solid-state
      structures and photophysical properties of mercury(II) complexes with (E)-N
      (pyridin-2-ylmethylidene)arylamines.
AB  - Ten neutral monomeric, dimeric and polymeric mercury(II) complexes of
      compositions HgX(2)L (3, 8), [HgX(2)L](2) (1, 2, 4-6 and 7), [Hg(NO(3))(2)L](n)
      (9) and {[Hg(N(3))(2)L](2)}(n) (10) where X = chloride, bromide, iodide, nitrate
      and azide, and L = (E)-N-(pyridin-2-ylmethylidene)arylamine, are described.
      Compounds 1-10 were characterized by elemental analyses, and IR and (1)H NMR
      spectroscopic studies. The solution-state photophysical properties of the
      complexes are highly dependent on the anions as seen in the fluorescence emission
      features. Single-crystal X-ray crystallography showed that the molecular
      complexes can aggregate into larger entities depending upon the anion coordinated
      to the metal centre. Iodide gives discrete monomeric complexes, chloride and
      bromide generate binuclear complexes formed through Hg-X-Hg bridges, while
      nitrate and azide lead to 1D coordination polymers. The significant differences
      in the observed aggregation patterns of the compounds indicate that the anions
      exert a substantial influence on the formation of the compounds. A further
      influence upon supramolecular aggregation is the presence of methyl substituents
      in L(3) and L(4), which generally enhances the probability of forming
      supramolecular pipi interactions involving the five-membered C(2)N(2)Hg chelate
      rings in their crystal structures.

PMID- 23172551
TI  - Chemical exposure among professional ski waxers--characterization of individual
      work operations.
AB  - BACKGROUND: Preparation of skis prior to skiing competitions involves several
      individual work operations and the use of a wide variety of chemically based ski
      waxing products to improve the performance of the skis, including products used
      after skiing for wax removal and ski sole cleaning. Modern ski waxes consist
      mainly of petroleum-derived straight-chain aliphatic hydrocarbons, perfluoro-n
      alkanes or polyfluorinated n-alkanes. The wax cleaning products contain solvents
      such as neat aliphatic hydrocarbons (aliphates) or a mixture with limonene.
      Different ski waxing work operations can result in contaminated workroom
      atmospheres. OBJECTIVES: The aim of this study was to assess the chemical
      exposures related to the individual ski waxing work operations by investigating
      the specific work operations in controlled model experiments. METHODS: Four main
      work operations with potential exposures were identified: (i) application of
      glider waxes, (ii) scraping and brushing of applied glider waxes, (iii)
      application of base/grip waxes, and (iv) ski sole cleaning. Aerosol particle
      masses were sampled using conical samplers equipped with 37-mm PVC, 5-um pore
      size filters and cyclones equipped with 37-mm PVC, 0.8-um pore size filters for
      the inhalable and the respirable aerosol mass fractions, respectively. For
      measurements of particle number concentrations, a Scanning Mobility Particle
      Sizer was used. RESULTS: Mean aerosol particle mass concentrations of 18.6 mg m(
      3) and 32.2 mg m(-3) were measured during application of glider wax powders in
      the respirable and in the inhalable aerosol mass fractions, respectively.
      Particle number concentration of ~900 000 particles cm(-3) was measured during
      application of glider wax powder products. Ski sole cleaning with products
      containing aliphates displayed solvent air concentrations up to 62.5 p.p.m.
      CONCLUSIONS: This study shows that the potential exposure to generated particles
      during ski waxing and ski preparation is considerable, especially during work
      using glide wax powders.

PMID- 23172552
TI  - Bariatric surgery: a best practice article.
AB  - Bariatric surgery can effectively reduce body weight and treat obesity associated
      metabolic diseases such as diabetes mellitus. There are also benefits for an
      individual's functional status and psychological health. A multi-disciplinary
      evaluation should be offered to the individual as the first essential step in
      considering bariatric surgery as a treatment. This evaluation should include a
      thorough medical assessment, as well as psychological and dietetic assessments.
      In this best practice article, we outline the current recommendations for
      referral for bariatric surgery. We also present the data for pre-operative
      assessment before bariatric surgery, with particular reference to cardiovascular
      disease and obstructive sleep apnoea. We describe the literature on outcomes
      after bariatric surgery, including the results for mortality, weight loss,
      remission of diabetes and associated endocrine disorders such as hypogonadism.
      Within this review, we will illustrate the impact of bariatric surgery on self
      image, psychological health and perceived health and functional status. Finally,
      we briefly detail the potential complications of bariatric surgery, and offer
      advice on post-operative care and surveillance.

PMID- 23172553
TI  - MicroRNAs are suitable for assessment as biomarkers from formalin-fixed paraffin
      embedded tissue, and miR-24 represents an appropriate reference microRNA for
      diffuse large B-cell lymphoma studies.
AB  - Tissue biopsy specimens in the form of formalin-fixed paraffin-embedded tissue
      (FFPET) represent a valuable resource for biomarker identification and
      validation. However, to date, they remain an underused asset due to uncertainty
      regarding RNA extraction and the reliability of downstream techniques, including
      quantitative RT-PCR. Recently, much interest has emerged in the study of
      microRNAs; small single-stranded RNAs with a role in transcriptional regulation,
      that are thought to be well preserved in FFPET. In this study, we show that
      microRNA expression is comparable between FFPET and matched fresh-frozen samples
      (miR-17-5p: p=0.01, miR-92: p=0.003), and demonstrate that no significant
      deterioration in expression occurs over prolonged FFPET storage (p=0.06).
      Furthermore, microRNA expression is equivalent dependant on RNA extraction method
      (p<0.001) or DNAse treatment of total RNA (p<0.001). Finally, we validate miR-24
      as a suitable reference microRNA for diffuse large B-cell lymphoma (DLBCL) FFPET
      studies.

PMID- 23172554
TI  - Concurrent primary angiosarcoma and invasive ductal carcinoma in the same breast.

PMID- 23172556
TI  - CVID patients with autoimmunity have elevated T cell expression of granzyme B and
      HLA-DR and reduced levels of Treg cells.
AB  - AIMS: Common variable immunodeficiency (CVID) is a primary antibody
      immunodeficiency with approximately 20% of patients reporting additional
      autoimmune symptoms. The primary aim of this study was to compare the levels of
      activated and regulatory T cells (Treg cells) in CVID patients in an attempt to
      clarify their possible interactions leading to the generation of autoimmunity.
      METHODS: Immunophenotyping of T cells was performed by flow cytometry using a
      whole blood approach. Surface expression of human leukocyte antigen HLA class II
      DR and intracellular levels of granzyme B in T cell subsets were assessed; Treg
      levels were measured using CD4 CD25, FOXp3 and CTLA-4. RESULTS: CVID patients had
      higher levels of granzyme B and HLA-DR on CD8(+) T cells compared with control
      values (mean of 59% vs 30% and 45% vs 21%, respectively). Patients also had
      reduced levels of Treg cells compared with control values (con mean=3.24% vs
      pat=2.54%). Patients with autoimmunity (5/23) had a similar level of T cell
      activation markers to the rest of the patients but with lower Treg cells (mean of
      1.1%) and reduced CD25 and CTLA-4 expression. Patients with autoimmunity had a
      higher ratio of activated to Treg cells compared with patients with no autoimmune
      symptoms. CONCLUSIONS: These results highlight that reduced levels of Treg cells
      were associated with elevated levels of activated T cells, suggesting that
      reduced Treg cells in these patients may have functional consequences in allowing
      exaggerated T cell responses.

PMID- 23172557
TI  - Novel controllable auxetic effect of linearly elongated supported polyelectrolyte
      multilayers with amorphous structure.
AB  - Polyelectrolyte multilayers (PEMs) deposited on flexible supports are promising
      candidates for many applications ranging from controlled wettability over stimuli
      responsive nanovalves to lithography free surface structuring. Since many
      potential applications involve elongation of these films, we investigated the
      effect of elongation on the PEM thickness and density with ellipsometry. To our
      surprise PEM films with known amorphous internal structure show auxetic behavior
      that depends on the PEM preparation condition. The measured refractive index was
      compared with simulated values using the Garnet equation to evaluate if the
      incorporation of water or air causes the observed phenomena.

PMID- 23172558
TI  - Necrotizing fasciitis following Soave procedure in Hirschsprung disease.

PMID- 23172559
TI  - Transmesenteric treves field hernia as a late complication in gastroschisis.

PMID- 23172555
TI  - EGFR mutation testing in lung cancer: a review of available methods and their use
      for analysis of tumour tissue and cytology samples.
AB  - AIMS: Activating mutations in the gene encoding epidermal growth factor receptor
      (EGFR) can confer sensitivity to EGFR tyrosine kinase inhibitors such as
      gefitinib in patients with advanced non-small-cell lung cancer. Testing for
      mutations in EGFR is therefore an important step in the treatment-decision
      pathway. We reviewed reported methods for EGFR mutation testing in patients with
      lung cancer, initially focusing on studies involving standard tumour tissue
      samples. We also evaluated data on the use of cytology samples in order to
      determine their suitability for EGFR mutation analysis. METHODS: We searched the
      MEDLINE database for studies reporting on EGFR mutation testing methods in
      patients with lung cancer. RESULTS: Various methods have been investigated as
      potential alternatives to the historical standard for EGFR mutation testing,
      direct DNA sequencing. Many of these are targeted methods that specifically
      detect the most common EGFR mutations. The development of targeted mutation
      testing methods and commercially available test kits has enabled sensitive, rapid
      and robust analysis of clinical samples. The use of screening methods, subsequent
      to sample micro dissection, has also ensured that identification of more rare,
      uncommon mutations is now feasible. Cytology samples including fine needle
      aspirate and pleural effusion can be used successfully to determine EGFR mutation
      status provided that sensitive testing methods are employed. CONCLUSIONS: Several
      different testing methods offer a more sensitive alternative to direct sequencing
      for the detection of common EGFR mutations. Evidence published to date suggests
      cytology samples are viable alternatives for mutation testing when tumour tissue
      samples are not available.

PMID- 23172560
TI  - A rare case of neonatal intussusception caused by cytomegalovirus.

PMID- 23172561
TI  - Diaphragmatic rupture with gastric volvulus after Heimlich maneuver.

PMID- 23172563
TI  - Decline in health status of extremely premature neonates with patent ductus
      arteriosus after second course of medical therapy.
AB  - INTRODUCTION: Many neonatal centers offer surgical ligation of patent ductus
      arteriosus (PDA) after two failed courses of pharmacologic therapy. This study
      compares health status of extremely premature (< 28 weeks gestation) neonates who
      failed medical therapy at the time of their second course of medical treatment
      versus operation. MATERIALS AND METHODS: A retrospective chart review was
      performed on neonates born at less than 28 weeks gestation who underwent PDA
      ligation after two rounds of medical therapy over a 7.5-year period. Measurements
      of health status at the time of the second course of medical therapy and the time
      of operation were compared. RESULTS: Neonates (n = 34) required less fraction of
      inspired oxygen (33.5 +/- 12.9% vs. 48.5 +/- 24%, p < 0.0001), had lower mean
      airway pressure (7.5 +/- 1.9 vs. 9.1 +/- 2.4 mm Hg, p < 0.0001), and were less
      likely to require vasopressor support (16.7 vs. 60%, p = 0.0126) at the time of
      the start of second course than at surgery. CONCLUSION: Our study suggests that
      extremely premature neonates show a decline in cardiopulmonary reserve between a
      second course of medical therapy and surgical intervention.

PMID- 23172564
TI  - A proposed classification for the spectrum of vanishing gastroschisis.
AB  - Infants born with gastroschisis in association with intestinal atresia are well
      described. We are the proposing the classification of vanishing gastroschisis. In
      this series of six cases, at one end of the spectrum is an infant having
      gastroschisis with a much narrower defect on the right side of umbilicus. The
      ischemic bowel loops were connected to bowel inside the abdomen by a fibrous band
      compressing the exposed bowel mesentery. On the other end of spectrum, an infant
      having extensive bowel atresia and complete closure of abdominal wall defect
      (gastroschisis) detected on antenatal ultrasound. These cases should raise
      awareness of this devastating complication in prenatal management of
      gastroschisis.

PMID- 23172565
TI  - Operative intercostal chest drain is not required following extrapleural or
      transpleural esophageal atresia repair.
AB  - BACKGROUND: Approximately half of the United Kingdom patients undergoing
      esophageal atresia (OA) repair have an operative intercostal chest drain (ICD)
      placed (2008 British Association of Pediatric Surgeons Congenital Anomalies
      Surveillance Study data). We reviewed our experience of OA repairs to evaluate if
      an ICD placement is necessary. METHODS: Patients with OA/distal tracheoesophageal
      fistula (TOF), treated between January 1990 and January 2010, were identified by
      retrospective review of a prospectively maintained electronic database and
      patient case notes. MAIN RESULTS: A total of 112 consecutive patients were
      identified, of whom 107 were included (73 male). Five were excluded as no case
      notes were available. Median birth weight was 2,597 g (range 924 to 4,245 g) and
      median gestational age was 38 weeks (27 to 41 weeks). Median age at discharge was
      22 days (3 to 440 days) and median follow-up was 3.5 years (0 to 18 years).
      Patients were analyzed in two groups-group 1 (n = 73) had an extrapleural (EP)
      repair, of which 23 had a pleural breach and group 2 (n = 34) had a purposeful
      transpleural (TP) approach (surgeon preference). Eleven patients (10%) had an
      operative ICD, of which six patients were in group 1 and five in group 2. These
      11 patients had an uncomplicated postoperative course and all operative ICD were
      removed within 48 hours of surgery. Of the 96 patients that did not have an
      operative ICD, only 2 (2%) required postoperative intervention. One patient, in
      group 2, had a postoperative ICD inserted for a simple pneumothorax at 12 hours
      and removed at 48 hours. The other patient, in group 1, had a clinically detected
      anastomotic leak after 48 hours and required operative repair. CONCLUSION: An
      operative ICD is not required following OA/distal TOF repair, whether the
      approach is EP or TP. ICD that were electively placed (in 10%) served no clinical
      purpose.

PMID- 23172566
TI  - Management of a complication of percutaneous gastrostomy in children.
AB  - AIM: "Buried bumper" is a complication of percutaneous gastrostomy related to the
      internal flange getting buried into the wall of the stomach. The aim of this
      study is to evaluate the management of this complication. METHODS: The surgical
      and interventional radiology database in our hospital from August 1999 to May
      2011 was analyzed. There were 2,007 patients who underwent percutaneous
      gastrostomy insertion. Notes for patients with buried bumper were reviewed. A
      telephonic interview with the parents of these children was performed with
      focused assessment of the care of the gastrostomy tube before the episode of
      buried bumper. Continuous data are reported as median (range). RESULTS: Twenty
      children developed buried bumper after gastrostomy insertion. They had a primary
      diagnosis of neurological (n = 14), metabolic (n = 3), or endocrine (n = 3)
      disorders. The age at presentation was 5.7 years (2 to 18 years); 2.5 years (1
      month to 5 years) after gastrostomy insertion. Ten children (50%) presented with
      symptoms related to buried bumper which included leakage around the gastrostomy
      (n = 4), pus, discharge or bleeding from the site (n = 5), stiffness on feeding
      (n = 3), and unable to push the flange (n = 1) (three children had more than one
      symptom). Ten children (50%) were asymptomatic and underwent routine change or
      removal of gastrostomy. In nine children, there was an attempt to remove the
      flange by interventional radiology but this was successful only in one. In the
      remaining 19 children, 4 had endoscopic removal while 15 children developed an
      inflammatory mass and required a laparotomy (n = 12) or laparoscopic-assisted
      excision (n = 3). CONCLUSION: Buried bumper is a rare complication of
      percutaneous gastrostomy. Inadequate postoperative care without appropriate
      mobilization is a factor leading to this preventable complication. Endoscopic
      removal is possible, failing which laparoscopic surgery should be considered.

PMID- 23172567
TI  - Lisfranc injury in adolescents.
AB  - BACKGROUND: There are only few studies of Lisfranc injuries in children and
      adolescents. The aim of this study was to evaluate the mid-term results of the
      operatively treated injuries. METHODS: Seven Lisfranc injuries of adolescents
      were treated operatively in the Tampere University Hospital between 2004 and
      2009. In four of the seven feet, the trauma comprised all the metatarsal bones.
      All patients were treated with open reduction and internal fixation. A
      questionnaire concerning the function and pain of the foot was sent to all the
      patients. RESULTS: In all but one case, the anatomical reduction was achieved and
      held during the follow-up. However, most patients claimed discomfort or constant
      harm in the injured foot at the end of the follow-up. Still, all the patients
      were able to run and no one needed to wear special shoes or any other kind of
      means. CONCLUSIONS: Lisfranc injuries in adolescents are likely to cause constant
      harm, even if the anatomical reduction is achieved.

PMID- 23172568
TI  - Manufactured volvulus.
AB  - BACKGROUND/PURPOSE: Malrotation with a common mesentery is the classical
      pathology allowing midgut volvulus to occur. There are only a few reports of
      small bowel volvulus without malrotation or other pathology triggering
      volvulation. We describe three cases of small bowel volvulus in very premature
      newborns with a perfectly normal intra-abdominal anatomy and focus on the
      question, what might have set off volvulation. METHODS: In 2005 to 2008, three
      patients developed small bowel volvulus without any underlying pathology.
      Retrospective patient chart review was performed with special focus on clinical
      presentation, preoperative management, intraoperative findings, and potential
      causative explanations. Mean follow-up period was 46 months. RESULTS: All
      patients were born between 27 and 31 weeks (mean 28 weeks) with a birth weight
      between 800 and 1,000 g (mean 887 g). They presented with an almost identical
      pattern of symptoms including sudden abdominal distension, abdominal tenderness,
      erythema of the abdominal wall, high gastric residuals, and radiographic signs of
      ileus. All of them were treated with intensive abdominal massage or pelvic
      rotation to improve bowel movement before becoming symptomatic. CONCLUSIONS:
      Properistaltic maneuvers including abdominal massage and pelvic rotation may
      cause what we term a "manufactured" volvulus in very premature newborns. Thus,
      this practice was stopped.

PMID- 23172569
TI  - Thoracoscopy versus thoracotomy for esophageal atresia and tracheoesophageal
      fistula repair: review of the literature and meta-analysis.
AB  - INTRODUCTION: The thoracoscopic approach to esophageal atresia (EA) with
      tracheoesophageal fistula (TOF) represents a challenging procedure whose real
      benefits remains unclear. Our purpose is to identify, through a meta-analysis,
      clinical evidence of the reliability of the thoracoscopic repair (TR) for EA/TOF
      compared with the open repair. MATERIALS AND METHODS: Defined PubMed search, with
      analysis of intraoperative and postoperative complications after open or
      thoracoscopic primary anastomosis for EA/TOF. RESULTS: Five articles met the
      criteria of meta-analysis, being comparative studies between TR and conventional
      open repair (COR), although they were retrospective. One article was excluded
      because it was available only in Japanese. We observed a slight prevalence,
      statistically insignificant, of the intraoperative and postoperative complication
      rate for TR: odds ratio (OR) 1.29. Excluding the conversion rate, the meta
      analysis between the complication rate for TR and COR did not show a significant
      difference (OR 0.64). Anastomosis's leaks and strictures considered together did
      not show a significant difference between the two techniques, p = not significant
      and OR of 0.56. Similar results were observed analyzing the single outcome of
      leaks and strictures; the meta-analysis did not show any significant differences
      with an OR, respectively, of 1.05 and 0.43. CONCLUSIONS: The effectiveness of the
      endoscopic technique for EA/TOF repair is indicated with outcomes not different
      from open surgery. A randomized controlled trial is needed in this field to
      indicate which procedure is superior, open or TR.

PMID- 23172570
TI  - Immediate intraportal transplantation of human bone marrow mesenchymal stem cells
      prevents death from fulminant hepatic failure in pigs.

PMID- 23172571
TI  - Laser-assisted printing of alginate long tubes and annular constructs.
AB  - Laser-assisted printing such as laser-induced forward transfer has been well
      studied to pattern or fabricate two-dimensional constructs. In particular, laser
      printing has found increasing biomedical applications as an orifice-free cell and
      organ printing approach, especially for highly viscous biomaterials and
      biological materials. Unfortunately, there have been very few studies on the
      efficacy of three-dimensional printing performance of laser printing. This study
      has investigated the feasibility of laser tube printing and the effects of sodium
      alginate concentration and operating conditions such as the laser fluence and
      laser spot size on the printing quality during laser-assisted printing of
      alginate annular constructs (short tubes) with a nominal diameter of 3 mm. It is
      found that highly viscous materials such as alginate can be printed into well
      defined long tubes and annular constructs. The tube wall thickness and tube outer
      diameter decrease with the sodium alginate concentration, while they first
      increase, then decrease and finally increase again with the laser fluence. The
      sodium alginate concentration dominates if the laser fluence is low, and the
      laser fluence dominates if the sodium alginate concentration is low.

PMID- 23172572
TI  - Clinical use of a new position-independent rebound tonometer.
AB  - PURPOSE: To compare intraocular pressure (IOP) measurements obtained by rebound
      tonometry (Icare PRO tonometer), applanation tonometry (Goldmann and Perkins
      tonometry), and dynamic contour tonometry in the upright and the supine
      positions, and to investigate the influence of axial length and central corneal
      thickness. METHODS: Ninety-nine right eyes of 99 patients with glaucoma or
      suspect for glaucoma, admitted to our department between November 2010 and
      January 2011 to obtain an IOP profile including supine measurements, were
      included in our study. IOP measurements were obtained in an upright position
      using an Icare PRO rebound (RTPRO), a Goldmann applanation (GAT), and a Pascal
      dynamic contour tonometer (DCT). In the supine position, IOP measurements were
      taken using the RTPRO and a Perkins hand-held applanation tonometer (PAT). The
      means and SDs for all tonometers were compared. Agreement between the tonometers
      was calculated using the Bland-Altman method. RESULTS: The mean IOPs obtained in
      the upright position were 17.7 +/- 8.0 mm Hg (RTPRO), 17.6 +/- 7.8 mm Hg (GAT),
      and 19.9 +/- 6.6 mm Hg (DCT). Correlation analysis of these data indicated a good
      correlation between IOP readings obtained using RTPRO and GAT (r=0.951; P<0.001),
      and RTPRO and DCT (r=0.897; P<0.001). Bland-Altman analysis revealed mean
      differences (bias) between RTPRO and GAT, and between RTPRO and DCT of 0.1 mm Hg
      and -1.8 mm Hg, with 95% limits of agreement of -3.6 to 3.8 mm Hg and -7.3 to 3.6
      mm Hg, respectively. In the supine position, the mean IOPs were 19.2 +/- 6.4 mm
      Hg using the RTPRO and 19.6 +/- 6.2 mm Hg using the PAT. CONCLUSIONS:
      Measurements obtained with the RTPRO, either in the upright or in the supine
      position, show good correlation and agreement with those provided by applanation
      and dynamic contour tonometry. The study was registered with the DRKS (German
      Clinical Trials Register; http://www.germanctr.de; DRKS00000581).

PMID- 23172573
TI  - Trans [O=Re(V)-OH] core stabilised by chelating N-heterocyclic dicarbene ligands.
AB  - Three Re(v) N-heterocyclic carbene complexes
      [ReO(OH)(L(Me))(2)][PF(6)](1.4)[ReO(4)](0.6),
      [ReO(OH)(L(iPr))(2)][PF(6)](1.4)[ReO(4)](0.6) and
      [ReO(OH)(L(Bn))(2)][PF(6)](1.3)[ReO(4)](0.7) (L(Me) = 1,1'-methylene-bis(3
      methylimidazole-2-ylidene); L(iPr) = 1,1'-methylene-bis(3-isopropylimidazole-2
      ylidene) and L(Bn) = 1,1'-methylene-bis(3-benzylimidazole-2-ylidene)) with trans
      oxo and hydroxo at axial positions have been synthesized.

PMID- 23172574
TI  - Synthesis of enantioenriched azo compounds: organocatalytic Michael addition of
      formaldehyde N-tert-butyl hydrazone to nitroalkenes.
AB  - The unprecedented diaza-ene reaction of formaldehyde N-tert-butyl hydrazone with
      nitroalkenes can be efficiently catalyzed by an axially chiral bis-thiourea to
      afford the corresponding diazenes in good to excellent yields (60-96%) and
      moderate enantioselectivities, up to 84 : 16 er; additional transformation of
      diazenes into their tautomeric hydrazones proved to be operationally simple and
      high-yielding, affording bifunctional compounds which represent useful
      intermediates for the synthesis of enantioenriched beta-nitro-nitriles and
      derivatives thereof.

PMID- 23172575
TI  - A review of chemical composition and nutritional value of wild-growing and
      cultivated mushrooms.
AB  - Fruit bodies of about 200 mushroom species are consumed throughout the world,
      preferably as a delicacy. Knowledge of their chemical composition, nutritional
      value and health-promoting effects has expanded dynamically during the last few
      years. Dry matter (DM) is low: commonly about 100 g kg-1 . The usual contents of
      protein, lipids and ash are 200-250, 20-30 and 80-120 g kg-1 DM, respectively.
      Various carbohydrates form the remaining DM. Nevertheless, great variations occur
      both among and within species. Energy is low, usually 350-400 kcal kg-1 of fresh
      fruit bodies. The nutritional contribution of mushroom protein derived from
      earlier data seems to be overestimated. Fat content is low with markedly
      prevailing in linoleic acid and oleic acid, while the proportion of n-3 fatty
      acids is nutritionally marginal. The main carbohydrates are chitin, glycogen,
      trehalose and mannitol. Information on fibre content and composition is limited.
      Health-promoting beta-glucans are an auspicious group of polysaccharides. High
      potassium content is characteristic of mushrooms. Several species can accumulate
      very high levels of both detrimental trace elements, particularly cadmium and
      mercury, and radiocaesium isotopes if growing on heavily polluted substrates.
      Mushrooms seem to be a considerable source of ergosterol, provitamin D2, and
      phenolids with antioxidative properties. Hundreds of flavour constituents have
      been identified, particularly with eight-carbon aliphatic chains. Data on changes
      of mushroom components under various preservation conditions and culinary
      treatments have been fragmentary. Even more limited is knowledge of nutrient
      bioavailability.

PMID- 23172577
TI  - The effect of naringin on early growth and development of the spheno-occipital
      synchondrosis as measured by the expression of PTHrP and Sox9--an in vitro model.
AB  - The aim of this study was to assess the effect of the flavonoid naringin on the
      growth of the spheno-occipital synchondrosis by quantifying the levels of
      expression of Sox9 and PTHrP in an in vitro mouse model. Fifty 1-day-old BALB/c
      mice were randomly assigned to experimental or control groups, and each group
      equally divided into five time frames (6, 24, 48, 72 and 168 hours). The mice
      were sacrificed with phenobarbitone sodium, and the spheno-occipital
      synchondroses dissected and cultured in control or experimental medium, with the
      experimental medium supplemented with 0.1 um naringin. Sections of the specimens
      underwent immunohistochemical staining for Sox9 and PTHrP, and the amount of
      expression was quantified using true-colour RGB (red-green-blue) computer
      assisted image-analysing system with digital imaging. Data analysis showed there
      was a significant increase of expression of Sox9 at 6 and 24 hours (P < 0.001)
      between experimental and control groups, however, there was no significant
      difference between the levels of expression of PTHrP between experimental and
      control groups at any of the time frames. There was a very weak correlation found
      in this study between the expression of PTHrP and Sox9. In conclusion, naringin
      enhances the growth of the spheno-occipital synchondrosis through over expression
      of Sox9. This is a successful in vitro model to study factors regulating the
      growth of the spheno-occipital synchondrosis.

PMID- 23172578
TI  - Efficiency of molar distalization with the XBow appliance related to second molar
      eruption stage.
AB  - To quantitatively evaluate on lateral cephalograms horizontal, vertical, and
      angular changes in the position of the maxillary first molar based on the
      presence and absence of erupted maxillary second molars when it is distalized
      with the XBow appliance. In this retrospective study, a total of 102
      consecutively treated cases were assessed. Lateral cephalograms were obtained at
      the start and after completion of active treatment with the XBow appliance. In
      one group of patients, distal movement of the maxillary first molars was
      performed before the eruption of maxillary second molars; in the other group of
      patients, both first and second maxillary molars were simultaneously moved
      distally. All cephalograms were superimposed on palatal plane using the method of
      best-fit. In order to compare the mean horizontal, vertical, and angular changes
      in molar position between the treatment groups and gender, a multivariate
      analysis of covariance (MANCOVA) was performed with the pre-treatment class II
      severity used as a covariate. Regression analysis was also performed to further
      explore any possible relationships between the predictor variables and the
      quantity and quality of distalization. A MANCOVA revealed that the eruption stage
      of the maxillary second molar did not have a significant effect on the change in
      position of the maxillary first molar after treatment with a XBow appliance. When
      distalizing maxillary first molars with a XBow appliance, there is no difference
      in the amount of distalization in patients with erupted and unerupted maxillary
      second molars.

PMID- 23172579
TI  - Reply: To PMID 21478298.

PMID- 23172580
TI  - Comparison of self- and conventional-ligating brackets in the alignment stage.

PMID- 23172581
TI  - 3D comparison of average faces in subjects with oral clefts.
AB  - This prospective cross-sectional, case-controlled morphometric study assessed
      three dimensional (3D) facial morphological differences between average faces of
      103 children aged 8-12 years; 40 with unilateral cleft lip and palate (UCLP), 23
      with unilateral cleft lip and alveolus (UCLA), 19 with bilateral cleft lip and
      palate (BCLP), 21 with isolated cleft palate (ICP), and 80 gender and age-matched
      controls. 3D stereophotogrammetric facial scans were recorded for each
      participant at rest. Thirty-nine landmarks were digitized for each scan, and x-,
      y-, z-coordinates for each landmark were extracted. A 3D photorealistic average
      face was constructed for each participating group and subjective and objective
      comparisons were carried out between each cleft and control average faces. Marked
      differences were observed between all groups. The most severely affected were
      groups where the lip and palate were affected and repaired (UCLP and UCLA). The
      group with midsagittal palatal deformity and repair (ICP) was the most similar to
      the control group. The results revealed that 3D shape analysis allows
      morphometric discrimination between subjects with craniofacial anomalies and the
      control group, and underlines the potential value of statistical shape analysis
      in assessing the outcomes of cleft lip and palate surgery, and orthodontic
      treatment.

PMID- 23172582
TI  - Three new xanthone derivatives from an algicolous isolate of Aspergillus wentii.
AB  - Three new xanthone derivatives, yicathin A (1), yicathin B (2), and yicathin C
      (3), and three known anthraquinone derivatives, alatinone (4), 1,5-dihydroxy-3
      methoxy-7-methylanthraquinone (5), and 5-hydroxy-1,3-dimethoxy-7
      methylanthraquinone (6), were isolated from the cultures of Aspergillus wentii pt
      1, an endophytic fungus isolated from the marine red alga Gymnogongrus
      flabelliformis. Their structures were unambiguously elucidated by NMR and mass
      spectroscopic methods as well as quantum chemical calculations. Compound 2 was
      active against Escherichia coli, and 3 could inhibit E. coli, Staphylococcus
      aureus, and Colletotrichum lagenarium.

PMID- 23172587
TI  - Current controversies in prenatal diagnosis 4: pregnancy complications due to
      placental vascular disease (pre-eclampsia, FGR): are we ready for prevention?

PMID- 23172583
TI  - Predictors of coronary lesions complexity in patients with stable coronary artery
      disease.
AB  - Only a few studies focused on the predictors of the SYNTAX score (SS). We
      evaluated the independent clinical predictors of SS in 436 consecutive patients
      with stable angina pectoris who underwent coronary angiography. Estimated
      glomerular filtration rate (eGFR) was calculated. The mean SS was 25.8 +/- 13.7.
      High-sensitivity C-reactive protein and low-density lipoprotein cholesterol
      levels gradually rise while high-density lipoprotein cholesterol (HDL-C),
      triglycerides, and eGFR levels gradually decline from low to high SS tertile.
      Multivariate logistic regression analysis revealed that diabetes (P = .005), left
      ventricular ejection fraction ([LVEF]; P < .001), previous statin use (P = .02),
      HDL-C level (P < .001), and eGFR (P < .001) were independent predictors of SS. In
      conclusion, the presence of diabetes mellitus, no previous statin use, and lower
      values of HDL-C, LVEF, and eGFR were independent predictors of coronary heart
      disease complexity. This study has been accepted to present at the 28th Turkish
      National Cardiology Congress.

PMID- 23172588
TI  - Comparative analysis of salt-responsive phosphoproteins in maize leaves using
      Ti(4+)--IMAC enrichment and ESI-Q-TOF MS.
AB  - Salinity is one of the most common abiotic stresses encountered by plants.
      Reversible protein phosphorylation is involved in plant defense processes against
      salinity stress. Here, we performed global phosphopeptide mapping through
      enrichment by our synthesized PVA-phosphate-Ti(4+)  IMAC coupled with subsequent
      identification by ESI-Q-TOF MS. A total of 104 peptide sequences containing 139
      phosphorylation sites were determined from 70 phosphoproteins of the control
      leaves. In contrast, 124 phosphopeptides containing 143 phosphorylated sites from
      92 phosphoproteins were identified in salt-stressed maize leaves. Compared with
      the control, 47 proteins were phosphorylated, 25 were dephosphorylated, and 45
      overlapped. Among the 72 differential phosphoproteins, 35 were known salt stress
      response proteins and the rest had not been reported in the literature. To
      dissect the differential phosphorylation, gene ontology annotations were
      retrieved for the differential phosphoproteins. The results revealed that cell
      signaling pathway members such as calmodulin and 14-3-3 proteins were regulated
      in response to 24-h salt stress. Multiple putative salt-responsive
      phosphoproteins seem to be involved in the regulation of photosynthesis-related
      processes. These results may help to understand the salt-inducible
      phosphorylation processes of maize leaves.

PMID- 23172589
TI  - Oil/Water interface charged by hydroxide ions and deprotonated fatty acids: a
      comment.
AB  - The effect of fatty acid impurities on the electrophoretic mobility of hexadecane
      in water emulsions is reinterpreted, occasioned by an error in the surface charge
      attributed to the fatty acids. The results are consistent with a surface charge
      contributed by both hydroxide ions and deprotonated fatty acids.

PMID- 23172590
TI  - Liver and heart MR relaxometry in iron loading: reproducibility of three methods.
AB  - PURPOSE: To compare the derived T2* values and reproducibility of three methods
      used to assess iron-loading in heart and liver. MATERIALS AND METHODS: In 23
      pediatric patients, liver and cardiac gradient-echo imaging datasets (within-exam
      repeated sequence pairs) were evaluated. Data analyses compared derived
      relaxation values (average of pairs) and coefficient of variation
      (reproducibility of pairs). RESULTS: T2* values showed differences across
      methods, with pixel-wise mean > average fit > pixel-wise median. Coefficient of
      variation was found to be lower (better) with pixel-wise median and average fit
      methods compared to the pixel-wise mean technique. Maximum coefficient of
      variation values were lowest for the pixel-wise median approach in both the heart
      and liver. CONCLUSION: Differences in derived T2* values between methods must be
      considered when comparing values to established magnetic resonance imaging (MRI)
      biopsy formulas. The pixel-wise median and average fit methods demonstrate
      substantial benefits in reproducibility compared to the pixel-wise mean method.
      Since minimal variation in measurement is critical for patient care, median
      processing of relaxometry data may be preferable in both tissue types.

PMID- 23172591
TI  - One-pot synthesis of (3-sulfopropyl methacrylate potassium)-silica hybrid
      monolith via thiol-ene click chemistry for CEC.
AB  - A novel (3-sulfopropyl methacrylate potassium)-silica hybrid monolithic column
      for CEC has been prepared by a simple one-pot approach based on efficient thiol
      ene click chemistry. In this process, the polycondensation of hydrolyzed
      alkoxysilanes and in situ click reaction of vinyl groups on 3-sulfopropyl
      methacrylate potassium and thiol groups on the precondensed siloxanes
      simultaneously occurred in a pretreated capillary. Homogeneous monolithic matrix
      with large through-pores tightly bonded to the inner wall of the capillary was
      shown by optical microscope and SEM. The minimum plate height of this hybrid
      monolithic column was determined as 3.9 MUm for thiourea. Anilines,
      alkylbenzenes, and phenols were well separated on this hybrid monolithic column
      by CEC, which indicated typical reversed-phase and cation-exchange
      chromatographic retention mechanisms of the column.

PMID- 23172592
TI  - Three-dimensional printing of stem cell-laden hydrogels submerged in a
      hydrophobic high-density fluid.
AB  - Over the last decade, bioprinting technologies have begun providing important
      tissue engineering strategies for regenerative medicine and organ
      transplantation. The major drawback of past approaches has been poor or
      inadequate material-printing device and substrate combinations, as well as the
      relatively small size of the printed construct. Here, we hypothesise that cell
      laden hydrogels can be printed when submerged in perfluorotributylamine
      (C(12)F(27)N), a hydrophobic high-density fluid, and that these cells placed
      within three-dimensional constructs remain viable allowing for cell proliferation
      and production of extracellular matrix. Human mesenchymal stem cells and MG-63
      cells were encapsulated into agarose hydrogels, and subsequently printed in high
      aspect ratio in three dimensional structures that were supported in high density
      fluorocarbon. Three-dimensional structures with various shapes and sizes were
      manufactured and remained stable for more than six months. Live/dead and DAPI
      stainings showed viable cells 24 h after the printing process, as well as after
      21 days in culture. Histological and immunohistochemical analyses after 14 and 21
      days revealed viable cells with marked matrix production and signs of
      proliferation. The compressive strength values of the printed gels consequently
      increased during the two weeks in culture, revealing encouraging results for
      future applications in regenerative medicine.

PMID- 23172593
TI  - Neutralizing antibody against granulocyte/macrophage colony-stimulating factor
      inhibits inflammatory response in experimental otitis media.
AB  - OBJECTIVES/HYPOTHESIS: Granulocyte/macrophage colony-stimulating factor is
      important in the pathogenesis of acute and chronic inflammatory disease. We
      hypothesized that granulocyte/macrophage colony-stimulating factor plays a
      pivotal role in middle ear inflammation and that neutralization of
      granulocyte/macrophage colony-stimulating factor would inhibit neutrophil
      migration into the middle ear and production of inflammatory mediators. STUDY
      DESIGN: Animal experiment. METHODS: We used transtympanic administration of
      lipopolysaccharide, a major component of gram-negative bacteria, into mice to
      induce an experimental otitis media. Control mice received injection of phosphate
      buffered saline into the middle ear cavity. Mice were systemically treated with
      granulocyte/macrophage colony-stimulating factor neutralizing antibody or control
      immunoglobulin G via intraperitoneal injection 2 hours before transtympanic
      injection of lipopolysaccharide or phosphate-buffered saline. Middle ear
      effusions were collected. Concentrations of interleukin (IL)-1beta, tumor
      necrosis factor (TNF)-alpha, keratinocyte chemoattractant, and macrophage
      inflammatory protein-2 in middle ear effusions were measured by enzyme-linked
      immunosorbent assay. Histologic examination of the middle ear was also performed.
      RESULTS: Transtympanic injection of lipopolysaccharide upregulated levels of
      granulocyte/macrophage colony-stimulating factor, IL-1beta, TNF-alpha,
      keratinocyte chemoattractant, and macrophage inflammatory protein-2 in the middle
      ear. Concentrations of cytokines and chemokines were significantly decreased in
      mice injected with granulocyte/macrophage colony-stimulating factor neutralizing
      antibody. Infiltration of inflammatory cells into the middle ear cavity induced
      by lipopolysaccharide was also significantly reduced by neutralization of
      granulocyte/macrophage colony-stimulating factor. CONCLUSIONS: Systemic injection
      of granulocyte/macrophage colony-stimulating factor neutralizing antibody
      inhibits the middle ear inflammation induced by lipopolysaccharide in mice. Our
      findings suggest that granulocyte/macrophage colony-stimulating factor may offer
      a novel therapeutic target for the management of intractable otitis media.

PMID- 23172594
TI  - Bayesian prediction for liver fibrosis staging: combined use of elastography and
      serum fibrosis markers.

PMID- 23172595
TI  - alpha-Hydroxy-beta-keto acid rearrangement-decarboxylation: impact on thiamine
      diphosphate-dependent enzymatic transformations.
AB  - The thiamine diphosphate (ThDP) dependent MenD catalyzes the reaction of alpha
      ketoglutarate with pyruvate to selectively form 4-hydroxy-5-oxohexanoic acid 2,
      which seems to be inconsistent with the assumed acyl donor role of the
      physiological substrate alpha-KG. In contrast the reaction of alpha-ketoglutarate
      with acetaldehyde gives exclusively the expected 5-hydroxy-4-oxo regioisomer 1.
      These reactions were studied by NMR and CD spectroscopy, which revealed that with
      pyruvate the observed regioselectivity is due to the rearrangement
      decarboxylation of the initially formed alpha-hydroxy-beta-keto acid rather than
      a donor-acceptor substrate role variation. Further experiments with other ThDP
      dependent enzymes, YerE, SucA, and CDH, verified that this degenerate
      decarboxylation can be linked to the reduced enantioselectivity of acyloins often
      observed in ThDP-dependent enzymatic transformations.

PMID- 23172596
TI  - Analytical goal setting in aneuploidy screening: within person biological
      variability of first trimester biochemical markers.
AB  - OBJECTIVE: To determine the average within person biological variability of free
      beta human chorionic gonadotrophin (free hCGbeta), intact hCG and pregnancy
      associated plasma protein A (PAPP-A), and to establish analytical goals for the
      measurement of these markers when used in first trimester screening. METHODS:
      Free hCGbeta, PAPP-A and intact hCG were measured on paired first trimester
      samples collected during the same pregnancy. Results were converted to Multiple
      of the Median (MoMs).The overall total variation at each day log was determined
      from a correlation of the marker MoMs in the log domain. Biological variation was
      calculated after taking into account analytical variation. RESULTS: The within
      person biological variability for free hCGbeta varied from 1.30% at 2 days
      separation to 5.25% at 5 days. For PAPP-A this was 1.96% and 5.03%, respectively,
      and for intact hCG this was 14.59% and 21.09%. All markers exhibit a rapid
      increase in biological variability as the time separation increased. CONCLUSIONS:
      Setting analytical goals for precision of measurement of first trimester
      biochemical markers from within person biological variability would suggest that
      free hCGbeta and PAPP-A needs to be measured with a precision of 2.5%, targets
      close to those set empirically by the Fetal Medicine Foundation and achieved in
      practice by some analytical system in routine use.

PMID- 23172598
TI  - [Effects of calorie information and nutrition traffic light on alimentation
      behaviour in public catering].
AB  - BACKGROUND: Due to the significant increase in overweight and obese people,
      action is needed to raise eating behaviour awareness. A significant main meal
      (lunch) is witnessing a growing trend in the catering (part of the out-of-home
      nutrition). The aim of this study is to determine whether the selection of lunch
      menus is affected through the display of nutritional information in the form of
      number of calories or a traffic light model. METHODS: In this exploratory study,
      quantitative data were collected in a cross-sectional design. In addition to the
      established measurement instruments, socio-demographic and socio-economic
      information of the subjects based on the study were evaluated. The survey took
      place in 2008 in 2 passes (time t A/t B). The identical lunch menu of a catering
      company was applied twice respectively for 4 weeks. In the second run (t B) the
      lunch menu contained additional nutritional information (big 4 instructions) in
      the form of calories or a traffic light nutrition. The test of group differences
      was based on scientific statistical analysis in SPSS. RESULTS: The overall
      results for the illustration of kilocalories or traffic light do not have a
      unique significance in the direction of a low average number of calories at the
      time t B in comparison to the time t A. The food participants, on average, choose
      a lower calorie-containing menu, when a combination of traffic light and calories
      is given. CONCLUSION: The nutrition behaviour is accompanied by an oversupply of
      unhealthy foods. Lunch participants are sensitised for the selection of healthier
      lunch menus by a traffic light nutrition information or calories information.
      Nutrition labelling for lunch menus in the form of calories nutrition information
      or a coloured traffic light could trigger preventive effects.

PMID- 23172597
TI  - [Managed competition in the health-care services - the Dutch experience].
AB  - For some years in Switzerland, in Germany and in the Netherlands some experience
      has been gathered with managed competition in health care. Efficiency reserves in
      the health service should be opened up by stronger competition orientation. Since
      the fundamental reform of the health insurance system in the Netherlands in 2006
      the longest experience with the new governance model exists in this country.
      Health system experts in Germany and Switzerland maybe interested to include the
      experiences from the Netherlands into their further reforms. The analysis of
      relevant statistics and publications shows that, after 6 years, the results of
      the health reform in the Netherlands are to be called rather "sobering up". The
      competition activities of the health insurances, the insured persons and the
      providers are rather weak. However the expenditures for health are rising
      continuously. The intended goals of managed competition (reduction of costs and
      efficiency increase) could not be achieved in the Netherlands so far. The role of
      the health insurance companies and the competition readiness of the insured
      persons were obviously overrated, at the same time as well as the market power of
      the provider was rather underestimated. 

PMID- 23172599
TI  - [On the risk of spread of E. coli/EHEC O104:H4 stx 2 positive bacteria via
      sewerage treatment plants during the 2011 EHEC outbreak in north Germany].
AB  - During an EHEC outbreak with E. coli O104:H4 stx2-pos in northern Germany 2
      sewage treatment plants (Cuxhaven and Stade) of highly affected areas were
      monitored for the presence of the outbreak strain. 7 efflux water samples were
      collected at 1 h and 6 h intervals. The overall E. coli content of the treated
      sewage water was approximately 35 000 CFU/100 mL in both treatment plants. Among
      these about 500 were ESBL-E. coli (1.4%). ESBL-Agar was used as selective medium
      as the outbreak strain is highly resistant to 3rd generation cephalosporins. From
      the ESBL-isolates 208 strains have been typed by molecular methods for markers
      specific to the outbreak strain (O104rfb -351 base pairs (bp), flic H4-201 bp,
      stx2-584 bp, Tellur D - 434 bp). No outbreak strain was detected. The number of
      E. coli O104:H4 stx2-pos was calculated to be less than 3 per 100 mL in the
      treated sewage at the time of the study. Therefore it can be concluded that there
      was no threat for bathers to fall sick with this highly pathogenic strain from
      possibly sewage-contaminated bathing waters during the outbreak. The national
      limit value of 1 800 E. coli in 100 mL offers a high safety margin. 

PMID- 23172600
TI  - [Social inequality, combined risk factors and self-assessed health status-
      analyses using the German microcensus 2009].
AB  - Based on the micro-census 2009 this study investigates the relationship between
      socio-economic status and a combination of the risk factors smoking behaviour and
      overweight and furthermore the relation between those risk factor combinations
      and health status. Based on a multinomial logistic regression it is shown that
      the combined risk factors are strongly related to socio-economic status. Age
      standardised conditional means show, furthermore, that the relationship between
      the combination of smoking behaviour and overweight and health status is
      moderately negative.

PMID- 23172608
TI  - 'Hard,' 'soft' and 'surrogate' endpoints in diabetes.

PMID- 23172609
TI  - Eu(fod)3 binding on the 1H-NMR spectra of bis(2'-ethylbenzoate)ethylene glycol
      podands.
AB  - The complexing and selective binding constants of Eu(fod)(3) with bis(2'
      ethylbenzoate)ethylene glycol podands having one to four oxyethylene groups was
      observed on their (1)H-NMR spectra at 250 MHz and 295 K in CDCl(3). The
      Eu(fod)(3) interaction displayed the selective binding role of oxygen on H(2)C-O
      CH(2) backbones with referring the (1)H chemical shifts. The estimated
      equilibrium constants, K(a), of 1:1 ratio of interactions were in accordance with
      the Eu(fod)(3) ionic radii to bind the oxygen sites depending on the size and
      conformation of the esters. Esters having one or two ethyleneoxy groups gave
      mainly 2:2 complexes using ester sites. The minimum lanthanide-podand ester
      distance displayed the maximum stability so that ester with four oxyethylene
      groups was found to bind the Eu(fod)(3) moderately, whereas ester with three
      oxyethylene groups showed a large induced chemical shift due to the stability of
      Eu(3+) complexes with larger ethyleneoxy groups.

PMID- 23172610
TI  - Exploring an orbitrap analyzer for the characterization of intact antibodies by
      native mass spectrometry.
AB  - Antibody profiling: native mass spectrometry analysis of intact antibodies can be
      achieved with improved speed, sensitivity, and mass resolution by using a
      modified orbitrap instrument. Complex mixtures of monoclonal antibodies can be
      resolved and their glycan "fingerprints" can be profiled. Noncovalent
      interactions are maintained, thus allowing antibody-antigen binding to be
      measured.

PMID- 23172611
TI  - A potential novel use for direct antiviral therapy.

PMID- 23172612
TI  - High biocompatibility and improved osteogenic potential of novel Ca-P/titania
      composite scaffolds designed for regeneration of load-bearing segmental bone
      defects.
AB  - Regeneration of load-bearing bone segments is still an open challenge due to the
      lack of biomaterials mimicking natural bone with a suitable chemicophysical and
      mechanical performance. This study proposes ceramic bone scaffolds made of beta
      tricalcium phosphate (beta-TCP) and titania (TiO2 ), developed from
      hydroxyapatite (HA) and TiO2 starting nanopowders, which exhibit high and
      interconnected macroporosity (>70 vol %). The scaffold composition was designed
      to achieve a synergistic effect of bioactivity/resorbability and mechanical
      properties suitable for load-bearing regenerative applications. The analysis of
      the morphology, structure, and mechanical strength of the scaffolds resulted in
      compression strength nearly twice that of commercially available HA bone grafts
      with similar structure (Engipore((r))). Biological characterization was carried
      out for human MG-63 osteoblast-like cells proliferation, activity, attachment,
      and viability. beta-TCP/TiO2 scaffolds show high proliferation rate, high
      viability, and high colonization rates. Moreover, an increased activity of the
      osteogenic marker alkaline phosphatase (ALP) was found. These results demonstrate
      that beta-TCP/TiO2 scaffolds have good potential as osteogenically active load
      bearing scaffolds; moreover, given the high and interconnected macroporosity as
      well as the resorbability properties of beta-TCP, these scaffolds may enhance in
      vivo osteointegration and promote the formation of new organized bone, thus
      resulting in very promising biomimetic scaffolds for long bone regeneration.

PMID- 23172613
TI  - Reactive graphene oxide nanosheets: a versatile platform for the fabrication of
      graphene oxide-biomolecule/polymer nanohybrids.
AB  - Graphene oxide (GO) nanosheets can be functionalized with reactive
      pentafluorophenyl ester via esterification of the carboxylic groups. The
      resulting reactive GO nanosheets provide a versatile platform for grafting of
      amino-containing polymers or biomolecules via ester-amine coupling. Coupling of
      poly[(9,9-dioctylfluorene)-alt-(4-amino-phenylcarbazole)] (PFCz-NH(2) ), amino
      terminated hyperbranched polyglycerol (HPG-NH(2) ), and lysozyme (Lyz) was
      illustrated. The Al/GO-g-PFCz/ITO sandwich thin-film device exhibits bistable
      electrical switching and rewritable memory effects. The GO-g-Lyz nanohybrids
      exhibit high bactericidal efficacy against S. aureus and E. coli, while the GO-g
      HPG nanohybrids exhibit reduced cytotoxicity toward 3T3 fibroblasts.

PMID- 23172614
TI  - Multiparametric MRI for prostate cancer localization in correlation to whole
      mount histopathology.
AB  - PURPOSE: To prospectively evaluate multiparametric magnetic resonance imaging
      (MRI) for accurate localization of intraprostatic tumor nodules, with whole-mount
      histopathology as the gold standard. MATERIALS AND METHODS: Seventy-five patients
      with biopsy-proven, intermediate, and high-risk prostate cancer underwent
      preoperative T2-weighted (T2w), dynamic contrast-enhanced (DCE) and diffusion
      weighted (DW) MRI at 1.5T. Localization of suspicious lesions was recorded for
      each of 24 standardized regions of interest on the different MR images and
      correlated with the pathologic findings. Generalized estimating equations (GEE)
      were used to estimate the sensitivity, specificity, accuracy, positive, and
      negative predictive value for every MRI modality, as well as to evaluate the
      influence of Gleason score and pT-stage. Tumor volume measurements on
      histopathological specimens were correlated with those on the different MR
      modalities (Pearson correlation). RESULTS: DW MRI had the highest sensitivity for
      tumor localization (31.1% vs. 27.4% vs. 44.5% for T2w, DCE, and DW MRI,
      respectively; P < 0.005), with more aggressive or more advanced tumors being more
      easily detected with this imaging modality. Significantly higher sensitivity
      values were obtained for the combination of T2w, DCE, and DW MRI (58.8%) as
      compared to each modality alone or any combination of two modalities (P <
      0.0001). Tumor volume can most accurately be assessed by means of DW MRI (r =
      0.75; P < 0.0001). CONCLUSION: Combining T2w, DCE, and DW imaging significantly
      improves prostate cancer localization.

PMID- 23172615
TI  - Electrokinetic supercharging preconcentration prior to CGE analysis of DNA:
      sensitivity depends on buffer viscosity and electrode configuration.
AB  - Aiming to high sensitivity DNA analysis by CGE, electrokinetic supercharging
      (EKS) approach was adopted in this article. EKS is known as an online
      preconcentration technique that combines electrokinetic sample injection (EKI)
      with transient ITP (tITP). Herein, two factors of buffer viscosity and electrode
      configuration were studied to further improve EKS performance. An ultralow
      viscosity Tris-Boric acid-EDTA (TBE) buffer solution, consisted of 2% low
      molecular-weight hydroxypropyl methyl cellulose (HPMC) and 6% mannitol and with
      pH 8.0 adjusted by boric acid, was applied. The boric acid would make a complex
      with mannitol and generates borate polyanion, which acts as the leading ion for
      tITP process. The new electrode configuration, a Pt ring around capillary, was
      modified on Agilent CE system to lead large amount sample introduction during
      EKS. The standard DNA sample of phiX174/HaeIII digest was used to evaluate the
      qualitative and quantitative abilities of the proposed strategy. The 170,000-fold
      highly diluted sample at concentration of 3.0 ng/mL was enriched by EKS and
      detected by normal UV detection method. The obtained LOD of the weakest peak of
      72 bp fragment was around 7.7 pg/mL, apparently improved more than 10,000-fold in
      comparison with conventional CGE with UV detection.

PMID- 23172617
TI  - Adiposity and glucose intolerance exacerbate components of metabolic syndrome in
      children consuming sugar-sweetened beverages: QUALITY cohort study.
AB  - BACKGROUND: Sugar-sweetened beverage (SSB) consumption is linked to weight gain
      and metabolic syndrome (MetS) components in children, but whether these
      associations are modified by excess weight and glucose tolerance status in
      children is not known. OBJECTIVE: The objective of this study was to examine the
      cross-sectional associations between SSB intake and MetS components among
      children above and below the 85th body mass index (BMI) percentile and those with
      and without impaired glucose tolerance (IGT). METHODS: Data were from the QUebec
      Adiposity and Lifestyle InvesTigation in Youth study (2005-2008). Caucasian
      children aged 8-10 years (n = 632) were recruited from 1040 primary schools in
      Quebec, Canada. SSB consumption was assessed by three 24-h dietary recalls, body
      fat mass by dual-energy absorptiometry, physical activity by 7-d accelerometer.
      Multivariate linear regressions were used, with age, sex, fat mass index and
      physical activity as covariates, including waist circumference (WC), systolic
      blood pressure (SBP), concentrations of triglyceride and high-density lipoprotein
      cholesterol and homeostasis model assessment of insulin resistance (HOMA-IR) as
      outcome variables. RESULTS: Among overweight children, a 100-mL higher SSB
      consumption was associated with a 0.1-unit higher HOMA-IR (P = 0.009) and a 1.1
      mm Hg higher SBP (P = 0.001). In children with IGT, a 100-mL higher SSB
      consumption was associated with a 1.4-mm Hg higher SBP and a 4.0-cm higher WC (P
      < 0.001). These associations were not observed among children <85th BMI
      percentile. CONCLUSIONS: Our results suggest that the association between higher
      SSB consumption and MetS components is more evident in overweight/obese and
      glucose-intolerant children.

PMID- 23172618
TI  - Bilateral pharyngocele surgery under local anesthesia: let the patient help the
      surgeon.

PMID- 23172619
TI  - [Anterior ischemic neuropathy and temporal arteriitis].

PMID- 23172620
TI  - [40 years of German-speaking ophthalomologists (DOP)].

PMID- 23172621
TI  - [Characteristics of pupil function in patients with dissociated vertical
      divergence].
AB  - Dissociated vertical divergence (DVD) is frequently associated with the infantile
      strabismus syndrome. There are different theories on the pathomechanism of this
      disorder, but none of them is generally accepted. Some authors believe that the
      slow upward movement of the covered eye is due to a different illumination of
      both retinae and consequently an unequal activity of the oculomotor nerve's
      nuclei. In one hypothesis a predominance of crossing pupillary tract fibres from
      the pretectal area to motor and parasympathetic nuclei of the oculomotor nerve
      was supposed. The consequence of this abnormal pathway in the midbrain would be a
      pronounced contraction anisocoria in patients with DVD. In contraction anisocoria
      the directly illuminated pupil contracts more strongly than the contralateral
      pupil without any efferent defect. In a small study we compared direct and
      indirect pupillary light reflexes in 11 DVD patients and 10 normal subjects. We
      found no significant differences of contraction anisocoria between the two
      groups. The results do not support the hypothesis of a different pupillary tract
      pathway in the midbrain of patients with DVD.

PMID- 23172622
TI  - [Cataract surgery in nanophthalmic eyes].
AB  - PURPOSE: The aim of this study was to determine the prevalence of nanophthalmos
      among cataract patients and to evaluate intraoperative and postoperative
      complications in nanophthalmic eyes. PATIENTS AND METHODS: Medical and operating
      records of all 3287 patients who had undergone clear cornea phacoemulsification
      cataract surgery with foldable acrylic IOL implantation during a period of two
      years (January 2009 to December 2010) were retrospectively reviewed.
      Nanophthalmos was diagnosed according to a shorter axial length than 20 mm, a
      shallow anterior chamber, hyperopia and scleral thickness greater than 1.7 mm as
      determined by echography. Before surgery all patients received an intravenous 20
      % mannitol solution. RESULTS: From 3287 eyes, six eyes of four patients were
      identified as nanophthalmic with an axial length below 20 mm and a scleral
      thickness greater than 1.7 mm. The prevalence of nanophthalmos was 0.18 %. The
      average hyperopia was + 7.87 D (+ 6.0 to + 9.50). The mean axial length was 19.58
      mm (18.94 to 20.00). The mean biometry calculation was 33.16 D (31.5 to 36.0). In
      all cases no complications were observed during the surgery. In two eyes a mild
      iritis was observed one day after surgery. During a follow-up of 3 months no
      further complications occurred. CONCLUSIONS: Surgical manipulation in a narrow
      and crowded anterior chamber in nanophthalmic eyes with increased vitreous
      pressure is always a challenge and must be performed by an experienced surgeon.
      Preoperative examination of scleral thickness and preoperative administration of
      hyper-osmotic solution for reduction of vitreous pressure are very important to
      prevent unexpected complications. There was no need for a prophylactic surgical
      procedure in our patients.

PMID- 23172623
TI  - [Nonparetic strabismus. 1].

PMID- 23172624
TI  - De novo fenestration of extra-cardiac Fontan Goretex conduit assisted by Inoue
      balloon.
AB  - De novo fenestration of Goretex conduit of extra-cardiac total cavopulmonary
      connection in the postoperative period is challenging, and is rarely reported. We
      report a 17-year-old boy with failing Fontan circuit in whom fenestration was
      created, aided by an Inoue balloon.

PMID- 23172625
TI  - Construction of a cytosolic firefly luciferase reporter cassette for use in PCR
      mediated gene deletion and fusion in Saccharomyces cerevisiae.
AB  - Monitoring promoter response to environmental changes using reporter systems has
      provided invaluable information regarding cellular state. With the development of
      in vivo luciferase reporter systems, inexpensive, sensitive and accurate promoter
      assays have been developed without the variability reported between in vitro
      samplings. Current luciferase reporter systems, however, are largely inflexible
      to modifications to the promoter of interest. To overcome problems in flexibility
      and stability of these expression vectors, we report the creation of a novel
      vector system which introduces a cytosol-localized Photinus pyralis luciferase
      [LUC*(-SKL)] capable of one-step, in vivo measurements into a promoter-reporter
      system via PCR-based gene deletion and fusion. After introduction of the reporter
      under HUG1 promoter control, cytosolic localization was confirmed by fluorescence
      microscopy. The dose-response of this novel construct was then compared with that
      of a similar HUG1Delta::yEGFP1 promoter-reporter system and shown to give a
      similar response pattern.

PMID- 23172626
TI  - Reversible sigma-dimerizations of persistent organic radical cations.
AB  - A class of well-defined reversible sigma-dimerizations of 9,10-dialkoxyanthracene
      radical cations are presented. Yellow crystals of the sigma-dimerized dication
      dissociate to purple solutions of monomeric radical cations in solution. The
      identity and stability of radical cations were unequivocally confirmed, providing
      evidence for reversible sigma-dimerizations of persistent radical cations of
      aromatic systems.

PMID- 23172627
TI  - In vivo metabolic imaging of insulin with multiphoton fluorescence of human
      insulin-Au nanodots.
AB  - Functional human insulin-Au nanodots (NDs) are synthesized for the in vivo
      imaging of insulin metabolism. Benefiting from its efficient red to near infrared
      fluorescence, deep tissue subcellular uptake of insulin-Au NDs can be clearly
      resolved through a least-invasive harmonic generation and two-photon fluorescence
      (TPF) microscope. In vivo investigations on mice ear and ex vivo assays on human
      fat tissues conclude that cells with rich insulin receptors have higher uptake of
      administrated insulin. Interestingly, the insulin-Au NDs can even permeate into
      lipid droplets (LDs) of adipocytes. Using this newly discovered metabolic
      phenomenon of insulin, it is found that enlarged adipocytes in type II diabetes
      mice have higher adjacent/LD concentration contrast with small-sized ones in wild
      type mice. For human clinical samples, the epicardial adipocytes of patients with
      diabetes and coronary artery disease (CAD) also show elevated adjacent/LD
      concentration contrast. As a result, human insulin-Au nanodots provide a new
      approach to explore subcellular insulin metabolism in model animals or patients
      with metabolic or cardiovascular diseases.

PMID- 23172628
TI  - Farnesoid X receptor inhibits gankyrin in mouse livers and prevents development
      of liver cancer.
AB  - One of the early events in the development of liver cancer is a neutralization of
      tumor suppressor proteins Rb, p53, hepatocyte nuclear factor 4alpha (HNF4alpha),
      and CCAAT/enhancer binding protein (C/EBP) alpha. The elimination of these
      proteins is mediated by a small subunit of proteasome, gankyrin, which is
      activated by cancer. The aim of this study was to determine the mechanisms that
      repress gankyrin in quiescent livers and mechanisms of activation of gankyrin in
      liver cancer. We found that farnesoid X receptor (FXR) inhibits expression of
      gankyrin in quiescent livers by silencing the gankyrin promoter through HDAC1
      C/EBPbeta complexes. C/EBPbeta is a key transcription factor that delivers HDAC1
      to gankyrin promoter and causes epigenetic silencing of the promoter. We show
      that down-regulation of C/EBPbeta in mouse hepatoma cells and in mouse livers
      reduces C/EBPbeta-HDAC1 complexes and activates the gankyrin promoter. Deletion
      of FXR signaling in mice leads to de-repression of the gankyrin promoter and to
      spontaneous development of liver cancer at 12 months of age. Diethylnitrosoamine
      (DEN)-mediated liver cancer in wild-type mice also involves the reduction of FXR
      and activation of gankyrin. Examination of liver cancer in old mice and liver
      cancer in human patients revealed that FXR is reduced, while gankyrin is elevated
      during spontaneous development of liver cancer. Searching for animal models with
      altered levels of FXR, we found that long-lived Little mice have high levels of
      FXR and do not develop liver cancer with age and after DEN injections due to
      failure to activate gankyrin and eliminate Rb, p53, HNF4alpha and C/EBPalpha
      proteins. CONCLUSION: FXR prevents liver cancer by inhibiting the gankyrin
      promoter via C/EBPbeta-HDAC1 complexes, leading to subsequent protection of tumor
      suppressor proteins from degradation.

PMID- 23172629
TI  - Histological characteristics of small hepatocellular carcinomas showing atypical
      enhancement patterns on gadoxetic acid-enhanced MR imaging.
AB  - PURPOSE: To define the histological characteristics of hepatocellular carcinomas
      (HCCs) showing atypical dynamic enhancement patterns on gadoxetic acid-enhanced
      dynamic magnetic resonance imaging (EOB-MRI). MATERIALS AND METHODS: We evaluated
      a total of 130 small (<= 3 cm) HCCs from 114 patients that were surgically
      removed after EOB-MRI. Two radiologists blinded to the histological findings
      retrospectively classified the HCCs into typical or atypical lesions. Gross
      morphology, nuclear histological grade, presence of vascular invasion, and
      capsule formation and infiltration were compared between the two groups using Chi
      square or Fisher tests. RESULTS: Atypical dynamic enhancement patterns were seen
      in 23 HCCs (17.7%). None of the atypical HCC showed vascular invasion (P <
      0.001). Atypical HCCs also showed more frequently smaller size (1.6 +/- 0.6 cm
      versus 2.1 +/- 0.6 cm, P = 0.001) with 86.9% (n = 20) of which 2 cm or less in
      diameter (P = 0.001), vaguely nodular appearance (56.5% vs 3.7%, P < 0.001), and
      nuclear grade I (69.6% versus 6.5%, P < 0.001), while less frequently showed
      capsule formation (26.1% versus 77.6%, P < 0.001) or capsular infiltration (16.7%
      versus 77.1%, P = 0.005). CONCLUSION: Atypical HCCs on EOB-MRI may be
      characterized by the absence of vascular invasion, smaller (< 2 cm or less) size,
      vaguely nodular appearance, and well differentiation, and infrequent capsule
      formation or capsular infiltration.

PMID- 23172632
TI  - Very fast electrophoretic separation on commercial instruments using a
      combination of two capillaries with different internal diameters.
AB  - A capillary formed by connecting a 9.7 cm-long separation capillary with id 25
      MUm with an auxiliary 22.9 cm-long capillary with id 100 MUm (coupled capillary)
      was tested for electrophoretic separation at high electric field intensities. The
      coupled capillary was placed in the cassette of a standard electrophoresis
      apparatus. It was used in the short-end injection mode for separation of a
      mixture of dopamine, noradrenaline, and adrenaline in a BGE of 20 mM citric
      acid/NaOH, pH 3.2. An intensity of 2.7 kV/cm was attained in the separation part
      of the capillary at a separation voltage of 30 kV, which is 2.9 times more than
      maximum intensity value attainable in a capillary with the same length with
      uniform id. At these high electric field intensities, the migration times of the
      tested neurotransmitters had values of 12.3-13.3 s and the attained separation
      efficiency was between 2350 and 2760 plates/s. It is thus demonstrated that an
      effective separation instrument - a coupled capillary - can be used for very
      rapid separation in combination with standard, commercially available
      instrumentation.

PMID- 23172634
TI  - Computational complexity in electronic structure.
AB  - In quantum chemistry, the price paid by all known efficient model chemistries is
      either the truncation of the Hilbert space or uncontrolled approximations.
      Theoretical computer science suggests that these restrictions are not mere
      shortcomings of the algorithm designers and programmers but could stem from the
      inherent difficulty of simulating quantum systems. Extensions of computer science
      and information processing exploiting quantum mechanics has led to new ways of
      understanding the ultimate limitations of computational power. Interestingly,
      this perspective helps us understand widely used model chemistries in a new
      light. In this article, the fundamentals of computational complexity will be
      reviewed and motivated from the vantage point of chemistry. Then recent results
      from the computational complexity literature regarding common model chemistries
      including Hartree-Fock and density functional theory are discussed.

PMID- 23172635
TI  - Phase II study of sorafenib in combination with cisplatin and 5-fluorouracil to
      treat recurrent or metastatic nasopharyngeal carcinoma.
AB  - BACKGROUND: We aimed to investigate the efficacy and tolerability of sorafenib
      combined with cisplatin and 5-fluorouracil (5-FU) in patients with recurrent or
      metastatic nasopharyngeal carcinoma (NPC). PATIENTS AND METHODS: It was a Simon
      two-stage designed trial. Chemotherapy-naive patients with recurrent or
      metastatic disease were enrolled. The regimen was sorafenib 400 mg orally b.i.d.,
      cisplatin 80 mg/m(2) i.v. day 1, and 5-FU 1000 mg/m(2)/day CIV for 4 days,
      repeated every 21 days. After a maximum of six cycles of chemotherapy, patients
      received maintenance of sorafenib. RESULTS: In total, 54 patients were enrolled.
      The objective response rate reached 77.8%, including 1 complete response and 41
      partial responses. The median progression-free survival was 7.2 months (95% CI
      6.8-8.4 months), and the median overall survival was 11.8 months (95% CI 10.6
      18.7 months). Major toxic effects included hand-foot skin reaction,
      myelosuppression, and gastrointestinal (GI) reaction. The incidence of hemorrhage
      was 22.2%, and one patient with liver metastases died of GI bleeding. Contrast
      enhanced ultrasonography was carried out in a subset of patients with liver
      metastases. CONCLUSION: Combination of sorafenib, cisplatin (80 mg/m(2)) and 5-FU
      (3000 mg/m(2)) was tolerable and feasible in recurrent or metastatic NPC. Further
      randomized trials to compare sorafenib plus cisplatin and 5-FU with standard dose
      of cisplatin plus 5-FU in NPC are warranted.

PMID- 23172637
TI  - The need for accredited training in gynaecological oncology: a report from the
      European Network of Young Gynaecological Oncologists (ENYGO).
AB  - BACKGROUND: Primary data on training experiences of European gynaecological
      oncology trainees are lacking. This study aims to evaluate trainee profile,
      satisfaction and factors affecting the training experience in gynaecological
      oncology in Europe. PATIENTS AND METHODS: A web-based anonymous survey sent to
      ENYGO members/trainees in July 2011. It included sociodemographic information and
      a 22-item (1-5 Likert scale) questionnaire evaluating training experience in
      gynaecological oncology. Chi-square tests were used for evaluating the
      independence of categorical variables and t-test (parametric)/Mann-Whitney (non
      parametric) tests for differences between two independent groups on continuous
      data. Cluster analysis was used to identify groupings in multivariate data and
      Cronbach's-alpha for questionnaire reliability. A multivariable linear regression
      model was used to assess the effect of variables on training satisfaction.
      RESULTS: One hundred and nineteen gynaecological-oncology trainees from 31
      countries responded. The mean age was 37.4 (S.D, 5.3) years and 55.5% were in
      accredited training posts. Two clusters identified in the cohort (Calinski
      Harabasz, CH = 47.35) differed mainly by accredited training (P = 0.003). The
      training-satisfaction score (TSS) had high reliability (Cronbach's alpha, 0.951)
      and was significantly associated with accredited posts (P < 0.0005), years of
      training (P = 0.001) and salary (P = 0.002). The TSS was independent of age (P =
      0.360), working hours (P = 0.620), overtime-pay (P = 0.318), annual leave (P =
      0.933), gender (P = 0.545) and marital status (P = 0.731). Accredited programme
      trainees scored significantly higher than others in 17 of 22 aspects of training.
      The areas of greater need included advanced laparoscopic/urological/colorectal
      surgery, radiation oncology, palliative-care, cancer genetics and research
      opportunities. CONCLUSIONS: Our data demonstrate the importance of accredited
      training and the need for harmonisation of gynaecological oncology training
      within Europe.

PMID- 23172636
TI  - Safety and efficacy of decitabine in combination with temozolomide in metastatic
      melanoma: a phase I/II study and pharmacokinetic analysis.
AB  - BACKGROUND: Temozolomide (TMZ) is widely used for chemotherapy of metastatic
      melanoma. We hypothesized that epigenetic modulators will reverse chemotherapy
      resistance, and in this article, we report studies that sought to determine the
      recommended phase 2 dose (RP2D), safety, and efficacy of decitabine (DAC)
      combined with TMZ. PATIENTS AND METHODS: In phase I, DAC was given at two dose
      levels: 0.075 and 0.15 mg/kg intravenously daily * 5 days/week for 2 weeks, TMZ
      orally 75 mg/m(2) qd for weeks 2-5 of a 6-week cycle. The phase II portion used a
      two-stage Simon design with a primary end point of objective response rate (ORR).
      RESULTS: The RP2D is DAC 0.15 mg/kg and TMZ 75 mg/m(2). The phase II portion
      enrolled 35 patients, 88% had M1c disease; 42% had history of brain metastases.
      The best responses were 2 complete response (CR), 4 partial response (PR), 14
      stable disease (SD), and 13 progressive disease (PD); 18% ORR and 61% clinical
      benefit rate (CR + PR + SD). The median overall survival (OS) was 12.4 months;
      the 1-year OS rate was 56%. Grade 3/4 neutropenia was common but lasted >7 days
      in six patients. CONCLUSIONS: The combination of DAC and TMZ is safe, leads to
      18% ORR and 12.4-month median OS, suggesting possible superiority over the
      historical 1-year OS rate, and warrants further evaluation in a randomized
      setting.

PMID- 23172638
TI  - Triple click reaction strategy for macromolecular diversity.
AB  - This Feature Article focuses on the rapidly emerging concept of the "triple click
      reactions" towards the design and synthesis of macromolecules with well-defined
      topology and chemical composition, and also precise molecular weight and narrow
      molecular weight distribution. The term "triple click reaction" used in this
      feature article is based on the utilization of three chemically and
      mechanistically different click reactions for polymer-polymer conjugation and
      post-modification of the polymers. Three sequential click reactions of which two
      are identical should not be considered to be triple click reactions. The triple
      click reaction strategy for polymer conjugation and post-modification of polymers
      is classified in this article based on the resultant architectures: linear and
      non-linear structures.

PMID- 23172639
TI  - Gestational weight gain in accordance to the IOM/NRC criteria and the risk for
      childhood overweight: a meta-analysis.
AB  - WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT: Gestational weight gain is a modifiable
      risk factor for childhood overweight. WHAT THIS STUDY ADDS: Exceeding the
      recommended gestational weight gain increases the risk for childhood overweight
      by about 30%. Interventions to avoid excessive weight gain are needed.
      BACKGROUND: Overweight and obesity in children are thought to be related to
      prenatal priming. Gestational weight gain (GWG) might be a potential modifiable
      risk factor for childhood overweight. OBJECTIVE: To quantify the associations of
      inadequate and excessive GWG with childhood overweight. METHODS: The electronic
      literature search in six databases was complemented by a hand search for relevant
      articles. Papers were selected and quality was assessed. The effect estimates of
      the individual studies were pooled using a random-effects model. RESULTS: The
      literature search yielded 1492 results in total, of which seven observational
      studies met the inclusion criteria. The studies had medium to good quality. The
      pooled estimate for the association between excessive GWG and childhood
      overweight yielded an odds ratio (OR) of 1.38 (95% confidence interval [CI]: 1.21
      1.57). The association between inadequate GWG and childhood overweight yielded an
      OR of 0.91 (95% CI: 0.85-0.98). CONCLUSION: These data provide evidence for at
      least a 21% risk for childhood overweight related to excessive GWG. Therefore,
      further efforts to design appropriate interventions against excessive GWG may
      appear warranted.

PMID- 23172640
TI  - Lattice energies for crystals of colloidal spheroids.
AB  - Attractive interactions between adjacent spheroids and excluded volume  effects
      favor their parallel alignment. Parallel spheroids can be arranged into a variety
      of densely packed two-dimensional and three-dimensional lattice configurations.
      All of these configurations turn out to have the same lattice energy. A similar
      degeneracy is also found for several classes of lattices with lower volume
      density. We discuss implications of this degeneracy for the stability of
      colloidal crystals consisting of spheroids.

PMID- 23172642
TI  - Editor's letter.

PMID- 23172641
TI  - Conservative treatment of early endometrial cancer.
AB  - Endometrial cancer is the most common cancer of the female genital tract in
      Europe and in the United States. Endometrial cancer has increased 21% in
      incidence since 2008, and the death rate has increased more than 100% over the
      past two decades. Approximately 15% of patients with endometrial cancer are pre
      menopausal. The aim of this review is to discuss the conservative management of
      endometrial cancer. A number of studies largely support the conservative
      treatment of endometrial carcinoma (EC) in women desiring future fertility. We
      focus on the role of progestin hormonal therapy, including the risks associated
      with non-standard care, appropriate candidate selection, expected outcomes,
      various progestin agents and recommended follow-up.

PMID- 23172644
TI  - SAR analysis and bioactive potentials of freshwater and terrestrial
      cyanobacterial compounds: a review.
AB  - Freshwater and terrestrial cyanobacteria resemble the marine forms in producing
      divergent chemicals such as linear, cyclic and azole containing peptides,
      alkaloids, cyclophanes, terpenes, lactones, etc. These metabolites have wider
      biomedical potentials in targeting proteases, cancers, parasites, pathogens and
      other cyanobacteria and algae (allelopathy). Among the various families of non
      marine cyanobacterial peptides reported, many of them are acting as serine
      protease inhibitors. While the micropeptin family has a preference for
      chymotrypsin inhibition rather than other serine proteases, the aeruginosin
      family targets trypsin and thrombin. In addition, cyanobacterial compounds such
      as scytonemide A, lyngbyazothrins C and D and cylindrocyclophanes were found to
      inhibit 20S proteosome. Apart from proteases, metabolites blocking the other
      targets of cancer pathways may exhibit cytotoxic effect. Colon and rectum,
      breast, lung and prostate are the worst affecting cancers in humans and are
      deduced to be inhibited by both peptidic and non-peptidic compounds. Moreover,
      the growth of infections causing parasites such as Plasmodium, Leishmania and
      Trypanosoma are well controlled by peptides: aerucyclamides A-D, tychonamides and
      alkaloids: nostocarboline and calothrixins. Likewise, varieties of cyanobacterial
      compounds tend to inhibit serious infectious disease causing bacterial, fungal
      and viral agents. Interestingly, portoamides, spiroidesin, nostocyclamide and
      kasumigamide are the allelopathic peptides determined to suppress the growth of
      toxic cyanobacteria and nuisance algae. Thus cyanobacterial compounds have a
      broad bioactive spectrum; the analysis of SAR studies will not only assist to
      find out the mode of action but also reveal bioactive key components. Thereby,
      developing the drugs bearing these bioactive skeletons to treat various illnesses
      is wide open.

PMID- 23172645
TI  - An improved short-lived fluorescent protein transcriptional reporter for
      Saccharomyces cerevisiae.
AB  - Ideal reporter genes for temporal transcription programmes have short half-lives
      that restrict their detection to the window in which their transcripts are
      present and translated. In an effort to meet this criterion for reporters of
      transcription in individual living cells, we adapted the ubiquitin fusion
      strategy for programmable N-end rule degradation to generate an N-degron version
      of green fluorescent protein (GFP) with a half-life of ~7 min. The GFP variant we
      used here (designated GFP*) has excellent fluorescence brightness and maturation
      properties, which make the destabilized reporter well suited for tracking the
      induction and attenuation kinetics of gene expression in living cells. These
      attributes are illustrated by its ability to track galactose- and pheromone
      induced transcription in S. cerevisiae. We further show that the fluorescence
      measurements using the short-lived N-degron GFP* reporter gene accurately predict
      the transient mRNA profile of the prototypical pheromone-induced FUS1 gene.

PMID- 23172647
TI  - [Reverse pupillary block following anterior crystalline lens dislocation].

PMID- 23172646
TI  - Standardized letter of recommendation for otolaryngology residency selection.
AB  - OBJECTIVES/HYPOTHESIS: Develop a standardized letter of recommendation (SLOR) for
      otolaryngology residency application that investigates the qualities desired in
      residents and the letter writer's experience. Compare this SLOR to narrative
      letters of recommendation (NLORs). STUDY DESIGN: Prospective SLOR/NLOR
      comparison. METHODS: The SLOR was sent to an NLOR writer for each applicant. The
      applicant's NLOR/SLOR pair was blinded and ranked in seven categories by three
      reviewers. Inter-rater reliability and NLOR/SLOR rankings were compared. Means of
      cumulative NLOR and SLOR scores were compared to our departmental rank list.
      RESULTS: Thirty-one SLORs (66%) were collected. The SLORs had higher inter-rater
      reliability for applicant's qualifications for otolaryngology, global assessment,
      summary statement, and overall letter ranking. Writer's background, comparison to
      contemporaries/predecessors, and letter review ease had higher inter-rater
      reliability on the NLORs. Mean SLOR rankings were higher for writer's background
      (P = .0007), comparison of applicant to contemporaries/predecessors (P = .0031),
      and letter review ease (P < .0001). Mean SLOR writing time was 4.17 +/- 2.18
      minutes. Mean ranking time was significantly lower (P < .0001) for the SLORs
      (39.24 +/- 23.45 seconds) compared to the NLORs (70.95 +/- 40.14 seconds). Means
      of cumulative SLOR scores correlated with our rank list (P = .004), whereas means
      of cumulative NLOR scores did not (P = .18). Means of cumulative NLOR and SLOR
      scores did not correlate (P = .26). CONCLUSIONS: SLORs require little writing
      time, save reviewing time, and are easier to review compared to NLORs. Our SLOR
      had higher inter-rater reliability in four of seven categories and was correlated
      with our rank list. This tool conveys standardized information in an efficient
      manner.

PMID- 23172648
TI  - [Spontaneous closure of traumatic macular hole with peculiar findings by optical
      coherence tomography].

PMID- 23172649
TI  - [Validity and reproducibility of sensor contact lens profiles in comparison to
      applanation tonometry in healthy eyes].
AB  - PURPOSE: The aim of this study was to check the validity of the profiles gained
      by a sensor contact lens in one eye. We compared these values with measurements
      done by applanation tonometry in the other eye. The measurements were done in
      different body postures and head positions. All examinations were repeated 2 to 8
      weeks afterwards to check the reproducibility. PATIENTS, MATERIAL AND METHODS:
      Five young healthy individuals with normal eyes had the intraocular pressure
      (IOP) of their right eye measured by applanation tonometry (Goldmann and Perkins)
      in different postures (45 minutes upright, 30 minutes supine, 20 minutes head
      body down and 30 minutes upright). Simultanously the left eye had a sensor
      contact lens, which measured the changes of the corneal curvature due to changes
      of the IOP within intervals of 5 minutes. Within 2-8 weeks all examinations were
      repeated completely in the same manner. RESULTS: After 45 minutes in upright
      position the mean IOP remained unchanged (14 mmHg), increased after 30 minutes in
      supine position (20 mmHg), increased again after 20 minutes in head-body-down
      position (22.4 mmHg) and came back to 14 mmHg after 30 minutes in upright
      position. A very similar profile was obtained in the repeat examinations. In
      contrast, the mean profiles gained by the sensor contact lens were not in a
      positive slope-like shape, but the mean values showed a flat or surprisingly, an
      even downward profile (head-body-down position). No statistical differences were
      found between all mean values of the first and repeat examinations. CONCLUSIONS:
      Intraocular pressure measurements gained by applanation tonometry showed the
      expected physiological positive slope profile during changes of the body and head
      positions (upright, supine, head-body-down). None of the profiles simultaneously
      gained by the sensor contact lens had a slope-like shape, but were flat or even
      downward. The reasons for the lacking validity between applanation tonometry and
      sensor contact lens cannot be explained. This makes the interpretation of
      Triggerfish profiles uncertain and they should therefore be done with caution.
      The reproducibility of the applanation tonometry values as well as of the sensor
      contact lens values was good and showed no significant differences.

PMID- 23172650
TI  - [Treatment of trichiasis and distichiasis with a biopsy punch -- an effective and
      practical method for eyelash follicle excision].
AB  - Localised distichiasis and trichiasis with resulting keratopathy leads to
      considerable impairment for the patient. We present a new technique which enables
      the surgeon to excise the lash with its follicle to prevent regrowth in a single
      movement. The procedure does not need any preparation, leaving the lid with
      minimal concomitant trauma which prevents recurrence of trichiasis. The excision
      is done with a dermatological biopsy punch (Kai Europe GmbH, Solingen, Germany).
      The punch is placed on the appropriate place perpendicular to the lid margin
      where the punch is driven 3-4 mm parallel to the lash. Histopathological
      diagnosis should be obtained not only to prove the principle of this technique:
      the entire biopsy material should be handed over to the pathologist as
      distichiasis and trichiasis can be the first sign of lid tumours. The presented
      technique of hair follicle excision with a biopsy punch is extremely effective.
      Success can be proven by the results of histological work-up of the biopsy
      material.

PMID- 23172651
TI  - [Screening for glaucoma by blue light-pattern ERG and OCT--are the methods
      comparable?].
AB  - BACKGROUND: Up to now, several examinations are necessary to identify early
      glaucoma. It is also possible to analyse the peripapillary retinal nerve fibre
      layer thickness by means of OCT. The loss of retinal ganglion cells can be
      measured by pattern ERG, therefore this method could be used for the detection of
      early glaucoma. This study compares the results of the blue light-pattern ERG
      with the Stratus OCT for glaucoma early recognition. PATIENTS AND METHODS: We
      studied 30 healthy test persons, 20 patients with glaucoma and 20 patients with
      suspected glaucoma. Each group was examined using eye pressure measurements,
      funduscopy, perimetry, pachymetry und analysing the retinal nerve fibre layer by
      the Stratus OCT. The diagnostic work-up was completed by the pattern ERG and an
      upgrade with a blue light filtering glass. The results of the blue light-pattern
      ERG and the OCT ("healthy" or "pathological") were compared in a cross table and
      the agreement between these two raters was measured by the Cohen's kappa
      coefficient. RESULTS: Pattern ERG and blue light-pattern ERG decrease with
      advancing age. After developing an age-matched calibration graph we defined
      standard values up to the age of 56 years. All included subjects were classified
      by Stratus OCT and blue light-pattern ERG as healthy. We recognised a significant
      reduction of the retinal nerve fibre layer thickness and the amplitude in the
      pattern ERG in the cluster of glaucoma patients. For most of them, a blue light
      pattern ERG could not be recorded. Nine out of 40 glaucoma suspect eyes were
      judged as "pathological". Regarding the amplitudes of the blue light-pattern ERG
      25 of 28 eyes under suspicion of glaucoma were assigned as "healthy". With the
      aid of the cross table we estimated a Cohen's kappa of 0.4. The sensitivity of
      the blue light-pattern ERG was computed to be 70 % and the specificity to be 97.7
      %. For the OCT we calculated the sensitivity to be 50 % and the specificity to be
      100 %. CONCLUSION: The blue light-pattern ERG correlates in 87 % of our cases
      with the OCT. Healthy test persons are certainly identified just as well as
      definitely glaucomatous patients. To distinguish people suspected of early
      glaucoma the blue light-pattern ERG can be used as an additional, fast and
      economic diagnostic procedure.

PMID- 23172652
TI  - Predictors and outcomes after transcatheter aortic valve implantation using
      different approaches according to the valve academic research consortium
      definitions.
AB  - OBJECTIVES: We report the results of a large single-center study evaluating
      predictors and outcomes after transcatheter aortic valve implantation (TAVI) with
      different devices and access routes according to the Valve Academic Research
      Consortium (VARC). BACKGROUND: The widespread adoption of TAVI warrants a
      systematic analysis of outcomes. Only few comprehensive data exist comparing
      different approaches as selected by a heart team. METHODS: TAVI was performed in
      326 consecutive patients (mean age 80.6 +/- 7.1 years, 55.5% female) at high risk
      for surgery with balloon-expandable and self-expanding devices through
      transfemoral or transapical access. Data were analyzed according to VARC
      endpoints; predictors of mortality were identified. RESULTS: All-cause mortality
      was 10.1% (30 days) and 29.9% (1 year) overall and comparable with regard to
      valve or access choice (P = 0.295) despite different risk profiles at baseline.
      Device success and 30-day safety endpoints were achieved in 87.1 and 21.2%.
      Myocardial infarction [hazard ratio (HR) 6.52], stage-2 and -3 acute kidney
      injury (HR 2.52 and 6.80) and major access site complications (HR 1.96) were
      independent predictors of 1-year all-cause mortality. Device success had a
      protective effect (HR 0.58). Baseline predictors included body mass index <20
      kg/m(2) (HR 3.20), NYHA class IV (HR 1.87), left ventricular ejection-fraction
      <30% (HR 2.30), higher STS-PROM scores (HR 1.05 per percent), and age (group 75
      85 years, HR 0.47). CONCLUSIONS: Comparable results were achieved with different
      devices and access routes in a heart team approach. Baseline and perioperative
      predictors of all-cause mortality were identified, contributing to the refinement
      of patient and device selection criteria for TAVI.

PMID- 23172653
TI  - Enhanced cortisol suppression following administration of low-dose dexamethasone
      in first-episode psychosis patients.
AB  - OBJECTIVE: Impaired regulation of the hypothalamic-pituitary-adrenal (HPA) axis
      and hyper-activity of this system have been described in patients with psychosis.
      Conversely, some psychiatric disorders such as post-traumatic stress disorder
      (PTSD) are characterised by HPA hypo-activity, which could be related to prior
      exposure to trauma. This study examined the cortisol response to the
      administration of low-dose dexamethasone in first-episode psychosis (FEP)
      patients and its relationship to childhood trauma. METHOD: The low-dose (0.25 mg)
      Dexamethasone Suppression Test (DST) was performed in 21 neuroleptic-naive or
      minimally treated FEP patients and 20 healthy control participants. Childhood
      traumatic events were assessed in all participants using the Childhood Trauma
      Questionnaire (CTQ) and psychiatric symptoms were assessed in patients using
      standard rating scales. RESULTS: FEP patients reported significantly higher rates
      of childhood trauma compared to controls (p = 0.001) and exhibited lower basal
      (a.m.) cortisol (p = 0.04) and an increased rate of cortisol hyper-suppression
      following dexamethasone administration compared to controls (33% (7/21) vs 5%
      (1/20), respectively; p = 0.04). There were no significant group differences in
      mean cortisol decline or percent cortisol suppression following the 0.25 mg DST.
      This study shows for the first time that a subset of patients experiencing their
      first episode of psychosis display enhanced cortisol suppression. CONCLUSIONS:
      These findings suggest there may be distinct profiles of HPA axis dysfunction in
      psychosis which should be further explored.

PMID- 23172654
TI  - The measurement of burden of care in serious mental illness: a qualitative
      review.
AB  - OBJECTIVE: Caring for someone with serious mental illness such as schizophrenia
      or bipolar disorder can result in considerable consequences for the caregiver.
      Carers often experience a range of negative emotions, impacts upon their physical
      and mental health, as well as financial strain. Resultant from these impacts,
      carers utilise medical services at a higher rate than their non-caregiving
      counterparts. Further, these consequences of caregiving can also impact upon the
      patient, resulting in an increase in psychopathology and relapse. Although the
      notion of burden has been studied for approximately 60 years, many flaws and
      inadequacies remain; most notably, a lack of agreement on the definition of the
      construct along with the poor psychometric properties of the burden assessment
      instruments. METHOD: This article reviews and evaluates the measures of burden of
      care that have been utilised with carers of people with a serious mental illness.
      A systematic search was conducted and all articles that had measured burden of
      care in schizophrenia or bipolar disorder in the database PUBMED were reviewed to
      ascertain the measure utilised. RESULTS: Ten different measures were subsequently
      identified and eight were reviewed; two were excluded on the basis that they had
      only been utilised once. CONCLUSIONS: It was apparent that many of the measures
      lacked a strong theoretical basis and sound psychometric properties. Further,
      some of the measures lacked utility, feasibility and specificity. The article
      concludes with recommendations for future research.

PMID- 23172655
TI  - Capacity of forensic patients to consent to treatment.
AB  - OBJECTIVE: Lack of capacity to consent to psychiatric treatment has been promoted
      as a better basis for compulsion than mental disorder plus risk of harm. Previous
      research has examined how that legal change would affect acutely unwell
      inpatients. There is little research on forensic patients. This research aimed to
      assess capacity to consent in forensic patients at different stages of recovery
      and to consider the implications of respecting their competent treatment
      decisions. METHOD: Capacity to consent was assessed in a cross-sectional sample
      of 109 forensic patients both in hospital and in community settings. RESULTS: The
      majority of participants (67.6%) had treatment-related decision-making capacity.
      Very few patients with capacity refused treatment. CONCLUSIONS: Change to a
      capacity-based legal approach may alter treatment for some forensic patients but
      would not necessarily increase risk of harm to others. The implications for
      release decisions are less clear.

PMID- 23172657
TI  - Atomically flat, large-sized, two-dimensional organic nanocrystals.
AB  - Large-sized, 2D single crystals of perylene are grown by both solution-cast and
      physical vapor transport methods. The crystals have a atomically flat
      parallelogram morphology and the aspect ratios of the lateral extension compared
      to the thickness are up to 10(3) . The atomically flat feature leads to good
      interface contact, making a single-crystal field-effect transistor with higher
      mobility. The mobility of atomically flat crystals can be 10(3) -10(4) times
      higher than rough crystals.

PMID- 23172656
TI  - Combination of multichannel single-voxel MRS signals using generalized least
      squares.
AB  - PURPOSE: To propose using the generalized least square (GLS) algorithm for
      combining multichannel single-voxel magnetic resonance spectroscopy (MRS)
      signals. MATERIALS AND METHODS: Phantom and in vivo brain MRS experiments on a 7
      T scanner equipped with a 32-channel receiver coil, as well as Monte Carlo
      simulations, were performed to compare the coefficient of variation (CV) of the
      GLS method with those of two recently reported spectral combination methods.
      RESULTS: Compared to the two existing methods, the GLS method significantly
      reduced CV values for the simulation, phantom, and in vivo experiments.
      CONCLUSION: The GLS method can lead to improved precision of peak quantification.

PMID- 23172658
TI  - The elusive halides VCl5, MoCl6, and ReCl6.
AB  - Vanadium pentachloride and molybdenum and rhenium hexachloride are all thermally
      unstable but can be prepared by metathesis from the corresponding fluorides with
      BCl(3) at low temperatures. MoCl(6) is structurally related to beta-WCl(6), and
      ReCl(6) to alpha-WCl(6). VCl(5) is a dimer in the solid state (V red, Cl green).

PMID- 23172660
TI  - Measurement of LDL-C after treatment with the CETP inhibitor anacetrapib.
AB  - Estimation of low-density lipoprotein cholesterol (LDL-C) using the Friedewald
      (FR) formula is often inaccurate when triglycerides are elevated or VLDL particle
      composition is altered. We hypothesized that LDL-C estimation by the FR formula
      and other measurement methods might also be inaccurate in individuals treated
      with a cholesteryl ester transfer protein (CETP) inhibitor. An assay comparison
      study was conducted using pre and posttreatment serum samples from 280 of the 811
      patients treated with the CETP inhibitor anacetrapib in the DEFINE study
      (determining the efficacy and tolerability of CETP inhibition with anacetrapib).
      After 24 weeks of treatment with anacetrapib, mean LDL-C values by FR formula,
      Roche direct method (RDM) and Genzyme direct method (GDM) deviated from that
      measured by the beta-quantification (BQ) reference method by -12.2 +/- 7.5, -10.2
      +/- 6.6, -10.8 +/- 8.8 mg/dl, respectively. After treatment with anacetrapib, the
      FR formula and detergent-based direct methods provided lower LDL-C values than
      those obtained by the BQ reference method. The bias by the FR formula appeared to
      be due to an overestimation of VLDL-C by the TG/5 component of the formula.
      Evaluation of the clinical significance of these findings awaits comprehensive
      lipid and cardiovascular outcome data from ongoing Phase III clinical studies of
      anacetrapib.

PMID- 23172659
TI  - ATPase activity of human ABCG1 is stimulated by cholesterol and sphingomyelin.
AB  - ATP-binding cassette protein G1 (ABCG1) is important for the formation of HDL.
      However, the biochemical properties of ABCG1 have not been reported, and the
      mechanism of how ABCG1 is involved in HDL formation remains unclear. We
      established a procedure to express and purify human ABCG1 using the suspension
      adapted human cell FreeStyle293-F. ABCG1, fused at the C terminus with green
      fluorescent protein and Flag-peptide, was solubilized with n-dodecyl-beta-D
      maltoside and purified via a single round of Flag-M2 antibody affinity
      chromatography. The purified ABCG1 was reconstituted in liposome of various lipid
      compositions, and the ATPase activity was analyzed. ABCG1 reconstituted in egg
      lecithin showed ATPase activity (150 nmol/min/mg), which was inhibited by
      beryllium fluoride. The ATPase activity of ABCG1, reconstituted in
      phosphatidylserine liposome, was stimulated by cholesterol and choline
      phospholipids (especially sphingomyelin), and the affinity for cholesterol was
      increased by the addition of sphingomyelin. These results suggest that ABCG1 is
      an active lipid transporter and possesses different binding sites for cholesterol
      and sphingomyelin, which may be synergistically coupled.

PMID- 23172661
TI  - Inhibition of hedgehog signaling attenuates carcinogenesis in vitro and increases
      necrosis of cholangiocellular carcinoma.
AB  - The Hedgehog signaling pathway plays a pivotal role during embryonic development,
      stem cell maintenance, and wound healing. Hedgehog signaling also is deregulated
      in many cancers. However, the role of this signaling pathway in the
      carcinogenesis of cholangiocarcinoma (CCC) is still unknown. In this study, we
      investigated the effects of Hedgehog inhibition by cyclopamine and 5E1 in
      cultured human CCC cell lines and in vivo using a xenograft mouse model. We also
      investigated the involvement of Hedgehog in epithelial to mesenchymal transition
      (EMT), migration, and CCC tumor growth. Sonic hedgehog (Shh) ligand was highly
      expressed in 89% of human CCC tissues and in CCC cell lines. Cyclopamine and 5E1
      treatments effectively inhibited cell proliferation, migration, and invasion by
      down-regulating the Hedgehog target genes glioblastoma 1 and glioblastoma 2. In
      vitro and in vivo, we detected an increase in epithelial marker, E-cadherin,
      after Hedgehog inhibition. In addition, we saw an increase in necrotic areas and
      a decrease in mitotic figures in cyclopamine and 5E1-treated CCC xenograft
      tumors. CONCLUSION: This study supports the presence of autocrine Hedgehog
      signaling in human CCC, where CCC cells produce and respond to Shh ligand.
      Blocking the Hedgehog pathway inhibited EMT and decreased the viability of CCC
      cells. In addition, cyclopamine and 5E1 inhibited the growth of CCC xenograft
      tumors.

PMID- 23172662
TI  - The use of a multichannel capillary for electrophoretic separations of mixtures
      of clinically important substances with contactless conductivity and UV
      photometric detection.
AB  - A fused-silica capillary with a common outer diameter, 360 MUm, but containing
      seven internal channels, each 28 MUm in diameter (a multichannel capillary), has
      been tested on electrophoretic separations of mixtures of dopamine, adrenaline,
      and noradrenaline, using a contactless conductivity and UV photometric detection.
      It has been demonstrated that the sensitivity of the detection of these
      neurotransmitters in multichannel capillary, in comparison with those obtained
      for a standard singlechannel capillary with similar cross-sectional area, is
      comparable to that for the contactless conductivity and is about 50% higher for
      the UV photometry. The sensitivity is increased without loss of the separation
      efficiency, in contrast to UV detection with bubble cell. Further possibilities
      of using a multichannel capillary are demonstrated on separations of mixtures of
      inorganic cations (K+, Ba2+, Na+, Mg2+, and Li+) and mixtures of glucose and
      ribose. The main advantage of multi-channel capillary in comparison with a
      singlechannel capillary with the same cross-sectional area becomes apparent in
      separations in background electrolytes of high conductivity.

PMID- 23172663
TI  - Genome-wide CpG island methylation analyses in non-small cell lung cancer
      patients.
AB  - DNA methylation is part of the epigenetic gene regulation complex, which is
      relevant for the pathogenesis of cancer. We performed a genome-wide search for
      methylated CpG islands in tumors and corresponding non-malignant lung tissue
      samples of 101 stages I-III non-small cell lung cancer (NSCLC) patients by
      combining methylated DNA immunoprecipitation and microarray analysis. Overall, we
      identified 2414 genomic positions differentially methylated between tumor and non
      malignant lung tissue samples. Ninety-seven percent of them were found to be
      tumor-specifically methylated. Annotation of these genomic positions resulted in
      the identification of 477 tumor-specifically methylated genes of which many are
      involved in regulation of gene transcription and cell adhesion. Tumor-specific
      methylation was confirmed by a gene-specific approach. In the majority of tumors,
      methylation of certain genes was associated with loss of their protein expression
      determined by immunohistochemistry. Treatment of NSCLC cells with epigenetically
      active drugs resulted in upregulated expression of many tumor-specifically
      methylated genes analyzed by gene expression microarrays suggesting that about
      one-third of these genes are transcriptionally regulated by methylation.
      Moreover, comparison of methylation results with certain clinicopathological
      characteristics of the patients suggests that methylation of HOXA2 and HOXA10 may
      be of prognostic relevance in squamous cell carcinoma (SCC) patients. In
      conclusion, we identified a large number of tumor-specifically methylated genes
      in NSCLC patients. Expression of many of them is regulated by methylation.
      Moreover, HOXA2 and HOXA10 methylation may serve as prognostic parameters in SCC
      patients. Overall, our findings emphasize the impact of methylation on the
      pathogenesis of NSCLCs.

PMID- 23172664
TI  - Experimental verification of microRNA targets is essential, prediction alone is
      insufficient.

PMID- 23172666
TI  - Benzyl isothiocyanate induces protective autophagy in human prostate cancer cells
      via inhibition of mTOR signaling.
AB  - Benzyl isothiocyanate (BITC) is a dietary chemopreventive agent that inhibits the
      growth of various human cancer cells by causing apoptotic cell death. In this
      study, we demonstrate that BITC not only induces apoptosis but also induces
      autophagy in human hormone-sensitive (Rv1) and -refractory (PC3) prostate cancer
      cells. In BITC-treated cells, the induction of autophagy was detected by
      monitoring the processing of an autophagy marker protein, microtubule-associated
      protein 1 light chain 3 (LC3), the aggregation of LC3 into granular structures
      and the formation of acidic organelles. Inhibition of autophagy using 3
      methyladenine increased BITC-induced apoptosis, whereas the administration of
      caspase inhibitor suppressed BITC-induced cell death. Our data also showed that
      BITC inhibits mammalian target of rapamycin (mTOR) kinase activity in a dose
      dependent manner. The expression of phospho-mTOR (Ser2481), an indicator of mTOR
      intrinsic catalytic activity, and phospho-UNC-51-like kinase 1 (Ser757), a direct
      substrate of mTOR, were decreased in BITC-treated cells. However, the increased
      expression of phospho-mTOR (Ser2448), phospho-AKT (Ser473) and antiapoptotic Bcl
      2 were detected only in PC3 cells at later stages of BITC treatment.
      Collectively, our results show that BITC induces a protective autophagy response
      in Rv1 and PC3 cells through inhibition of the mTOR signaling pathway. Activation
      of the AKT survival pathway was only observed in PC3 cells, representing a
      resistance mechanism of advanced prostate cancer upon BITC treatment. These
      findings could potentially contribute to the beneficial effect of BITC in
      prostate cancer treatments.

PMID- 23172665
TI  - STAT3 is involved in esophageal carcinogenesis through regulation of Oct-1.
AB  - The transcription factor signal transducer and activator of transcription 3
      (STAT3) contributes to cell proliferation, apoptosis and motility in human cancer
      cells. We aim to elucidate the function of STAT3 in esophageal carcinogenesis
      process and molecular mechanisms. We showed that hyperactivated STAT3 in
      esophageal carcinogenesis tissues correlated with the overexpression of octamer
      transcription factor-1 (Oct-1). High STAT3 phosphorylation correlated with
      shorter survival compared with low STAT3 phosphorylation. STAT3 and Oct-1
      expression levels affected the proliferation and colony formation of Eca-109
      esophageal squamous cell carcinoma cells by altering Erk and Akt activation.
      Nevertheless, STAT3 regulated the migration and invasion of esophageal squamous
      cell carcinoma cells independent of Oct-1. In conjunction with Oct-1, STAT3
      inhibited apoptosis in esophageal squamous cell carcinoma cells. Constitutively
      activated STAT3 in normal human esophageal epithelium cells (HET-1A) elevated Oct
      1 expression,and promoted proliferation and decreased apoptosis. STAT3 activated
      HET-1A cells to form tumors in vivo, suggesting that overactivated STAT3 is
      sufficient for carcinogenesis. We further confirmed the colocalization of STAT3
      and Oct-1 in the nucleus and found that STAT3 regulates the transcription and
      expression of Oct-1 by directly targeting its promoter. Activated STAT3 also
      upregulated many genes associated with Oct-1. Together, our results indicate that
      STAT3 plays a crucial role in esophageal carcinogenesis by regulating the cell
      proliferation and apoptosis in conjunction with Oct-1.

PMID- 23172667
TI  - Ochratoxin A-induced cell proliferation and tumor promotion in mouse skin by
      activating the expression of cyclin-D1 and cyclooxygenase-2 through nuclear
      factor-kappa B and activator protein-1.
AB  - Our prior studies have indicated that ochratoxin A (OTA), a mycotoxin, has skin
      tumor initiating activity. In the present investigation, skin tumor promoting
      activity of OTA and the mechanism/(s) involved therein was undertaken. A single
      topical application of OTA (100 nmol/mouse) caused significant enhancement in
      short-term markers of skin tumor promotion such as ornithine decarboxylase
      activity, DNA synthesis, hyperplasia as well as expression of cyclin-D1 and COX-2
      in mouse skin. In a two-stage mouse skin tumorigenesis protocol, twice-weekly
      exposure of OTA (50 nmol/mouse) to 7,12-dimethylbenz[alpha]anthracene (120
      nmol/mouse) initiated mice skin for 24 weeks leads to tumor formation. Further,
      exposure of primary murine keratinocytes (PMKs) with non-cytotoxic dose of OTA
      (5.0 uM) caused (i) significant enhancement of DNA synthesis, (ii) enhanced
      phosphorylation and subsequent activation of epidermal growth factor receptor
      (EGFR) and its downstream signaling pathways viz Akt, ERK1/2, p38 and JNK mitogen
      activated protein kinases (MAPKs), (iii) overexpression of c-jun, c-fos, cyclin
      D1 and COX-2 and (iv) increased binding of nuclear factor-kappaB (NF-kappaB) and
      AP-1 transcription factors to the promoter region of cyclin-D1 and COX-2 genes.
      It was also observed that knocking down the messenger RNA expression of NF
      kappaB, c-jun, c-fos, cyclin-D1 and COX-2 results in significant inhibition in
      OTA-induced PMKs proliferation. These results suggest that OTA has cell
      proliferative and tumor-promoting potential in mouse skin, which involves EGFR
      mediated MAPKs and Akt pathways along with NF-kappaB and AP-1 transcription
      factors and that cyclin-D1 and COX-2 are the target genes responsible for tumor
      promoting activity of OTA.

PMID- 23172668
TI  - Selective Cox-2 inhibitor celecoxib induces epithelial-mesenchymal transition in
      human lung cancer cells via activating MEK-ERK signaling.
AB  - Increasing evidence has suggested that high expression level of cyclooxygenase-2
      (Cox-2) is associated with the malignancies of non-small cell lung cancer
      (NSCLC), leading to a rationale of applying Cox-2 inhibitors as adjuvant therapy
      in the treatment of NSCLC. However, the addition of celecoxib, a selective Cox-2
      inhibitor, to chemotherapy in clinical trials failed to benefit the survival of
      NSCLC patients, which urges the investigation to re-evaluate this strategy for
      NSCLC treatment. In this study, we observed that celecoxib treatment at
      clinically relevant concentrations induced epithelial-mesenchymal transition
      (EMT) in NSCLC cells regardless of Cox-2 status, which, however, was not
      recapitulated using another Cox-2 inhibitor, etodolac. Celecoxib-stimulated EMT
      in turn promoted cell invasion and rendered cells resistant to chemotherapy.
      Further mechanistic investigation by disrupting the integrity of signaling
      pathways using specific inhibitors or RNA interference revealed that celecoxib
      induced EMT in NSCLC cells is indispensable of transforming growth factor
      beta1/Smad signaling. Instead, the activated MEK/ERK/SNAIL1 signaling largely
      accounted for celecoxib-induced EMT. Taken together, our study reveals the
      diverse impacts of Cox-2 inhibitors on EMT in NSCLC cells independent of Cox-2
      inhibition, where celecoxib treatment leads to metastasis and chemoresistance via
      EMT induction. These findings reveal the increased risks of cancer metastasis and
      chemoresistance by applying Cox-2 inhibitors, celecoxib in particular, in
      clinical trials of NSCLC treatment and urge intensive preclinical assessment
      before proceeding to clinical application.

PMID- 23172673
TI  - The bound coherent neutron scattering lengths of the oxygen isotopes.
AB  - The technique of neutron interferometry was used to measure the bound coherent
      neutron scattering length b(coh) of the oxygen isotopes (17)O and (18)O. From the
      measured difference in optical path between two water samples, either H(2)(17)O
      or H(2)(18)O versus H(2)(nat)O, where nat denotes the natural isotopic
      composition, we obtain b(coh,(17)O) = 5.867(4) fm and b(coh,(18)O) = 6.009(5) fm,
      based on the accurately known value of b(coh,(nat)O) = 5.805(4) fm which is equal
      to b(coh,(16)O) within the experimental uncertainty. Our results for b(coh,(17)O)
      and b(coh,(18)O) differ appreciably from the standard tabulated values of 5.6(5)
      fm and 5.84(7) fm, respectively. In particular, our measured scattering-length
      contrast of 0.204(3) fm between (18)O and (nat)O is nearly a factor of 6 greater
      than the tabulated value, which renders feasible neutron diffraction experiments
      using (18)O isotope substitution and thereby offers new possibilities for
      measuring the partial structure factors of oxygen-containing compounds, such as
      water.

PMID- 23172669
TI  - Histone deacetylase inhibitor suberoylanilide hydroxamic acid suppresses the pro
      oncogenic effects induced by hepatitis B virus pre-S2 mutant oncoprotein and
      represents a potential chemopreventive agent in high-risk chronic HBV patients.
AB  - Chronic hepatitis B virus (HBV) infection is the major cause of hepatocellular
      carcinoma (HCC). The pre-S(2) mutant large HBV surface antigen (LHBS) in type II
      ground glass hepatocytes (GGHs) has been recognized as an emerging viral
      oncoprotein; it directly interacts with the c-Jun activation domain-binding
      protein 1 (JAB1) and subsequently causes hyperphosphorylation of the tumor
      suppressor retinoblastoma and, consequently, leads to disturbed cell cycle
      progression. The interaction of the pre-S(2) mutant LHBS with JAB1 could provide
      a potential target for chemoprevention. In this study, we found that the
      preneoplastic type II GGHs showed a significant decrease of the cyclin-dependent
      kinase inhibitor p27(Kip1), which serves as a marker for pre-S(2) mutant-JAB1
      complex formation. The histone deacetylase (HDAC) inhibitor suberoylanilide
      hydroxamic acid (SAHA) elevated expression of the tumor-suppressor thioredoxin
      binding protein 2 (TBP2), which subsequently enhanced the JAB1-TBP2 interaction
      and abolished the pre-S(2) mutant LHBS-induced degradation of p27(Kip1), which,
      in turn, recovered the normal cell cycle checkpoint. The pre-S(2) mutant LHBS
      induced pro-oncogenic effects: increased cell proliferation, nuclear/cytoplasmic
      ratio and proliferating cell nuclear antigen expression, were all greatly
      ameliorated after SAHA treatments, which suggested SAHA as a promising
      chemopreventive agent for the pre-S(2) mutant oncoprotein-induced HCC. In
      conclusion, this study provides the mechanism of histone deacetylase (HDAC)
      inhibitor in preventing the pre-S(2) mutant-induced oncogenic phenotype. The HDAC
      inhibitor SAHA is therefore a potential chemopreventive agent for high-risk
      chronic HBV patients who may develop HCC.

PMID- 23172674
TI  - Species identification of Wickerhamomyces anomalus and related taxa using beta
      tubulin (beta-tub) DNA barcode marker.
AB  - Wickerhamomyces anomalus is used in food and feed processing, although the
      species has been reported as an opportunistic human pathogen, predominantly in
      neonates. Neither phenotypic nor the most frequently applied genotypic marker
      (D1/D2 LSU ribosomal DNA) provide sufficient resolution for accurate
      identification of this yeast. In this study, the beta-tubulin gene was used for
      species identification by direct DNA sequencing and as marker in a species
      specific PCR assay. The results showed that all examined W. anomalus strains were
      clearly distinguished from the closely related species by comparative sequence
      analysis of the beta-tubulin gene. In addition, the species-specific primers were
      also developed based on the beta-tubulin gene, which was employed for polymerase
      chain reaction with the template DNA of Wickerhamomyces strains. A single 218 bp
      species-specific band was found only in W. anomalus. Our data indicate that the
      phylogenetic relationships between these strains are easily resolved by
      sequencing of the beta-tubulin gene and combined with species-specific PCR assay.

PMID- 23172675
TI  - Improved correction for gradient nonlinearity effects in diffusion-weighted
      imaging.
AB  - PURPOSE: To provide an improved correction for gradient nonlinearity (GN) effects
      in diffusion-weighted imaging (DWI). These effects produce spatially varying
      apparent diffusion coefficient (ADC), a result that will be significant in large
      field-of-view imaging, and may be confounded by distortion and concomitant fields
      related to the DWI acquisition. MATERIALS AND METHODS: The effect of more
      accurate gradient field maps on GN correction (GNC) of ADC was evaluated. A
      simulation compared GN effects in commonly imaged anatomy. A temperature
      controlled phantom was imaged at positions 0 cm and 11 cm from isocenter and in
      two whole-body MRI systems at 1.5T with different patient bore diameters (55 cm
      and 60 cm). Varying correction methods were applied to determine the errors from
      spatial variance and interscanner reproducibility. RESULTS: As compared to
      conventional fifth-order spherical harmonics, a seventh-order GNC improved ADC
      accuracy by 1%. The combination of GNC with a dual-spin-echo pulse sequence and a
      retrospective concomitant field correction reduced ADC error due to spatial
      variance from 9.5% to 1.8% (55 cm bore) and from 4.2% to 1.8% (60 cm bore). The
      error in ADC attributed to interscanner reproducibility was reduced from 5.8% to
      0.15% (at isocenter) and from 10% to 0.63% (11 cm from isocenter). CONCLUSION:
      GNC in DWI improved spatial accuracy and interscanner reproducibility of ADC.

PMID- 23172676
TI  - Venous blood ammonia can be associated with cerebral blood flow in hepatic
      encephalopathy.

PMID- 23172677
TI  - A novel approach for surgical repair of dehiscent high jugular bulb.

PMID- 23172678
TI  - Cor triatriatum: an unusual cause of elevated pulmonary capillary wedge pressure
      in a child with tetralogy of Fallot.
AB  - The coexistence of cor triatriatum and tetralogy of Fallot (TOF) is rare.
      Preoperative identification of cor triatriatum may be difficult owing to reduced
      pulmonary blood flow in patients with TOF. However, it is imperative to identify
      this rare combination as failure to identify obstruction to pulmonary venous
      egress may result in persistent pulmonary venous hypertension postoperatively.
      The authors discuss hemodynamic aspects of this rare coexistence in a 14-month
      old child in whom pulmonary capillary wedge pressure was elevated despite right
      ventricular outflow obstruction.

PMID- 23172679
TI  - Asymmetric hydrogenation of alpha,alpha'-disubstituted cycloketones through
      dynamic kinetic resolution: an efficient construction of chiral diols with three
      contiguous stereocenters.
AB  - Chiral diols with three contiguous stereocenters were synthesized by a highly
      enantioselective ruthenium-catalyzed asymmetric hydrogenation of racemic
      alpha,alpha'-disubstituted cycloketones involving dynamic kinetic resolution.
      This new catalytic asymmetric method provides a concise route to the alkaloid (+)
      gamma-lycorane.

PMID- 23172680
TI  - Correlations between the dielectric properties and exterior morphology of cells
      revealed by dielectrophoretic field-flow fractionation.
AB  - Although dielectrophoresis (DEP) has great potential for addressing clinical cell
      isolation problems based on cell dielectric differences, a biological basis for
      predicting the DEP behavior of cells has been lacking. Here, the dielectric
      properties of the NCI-60 panel of tumor cell types have been measured by
      dielectrophoretic (DEP) field-flow fractionation, correlated with the exterior
      morphologies of the cells during growth, and compared with the dielectric and
      morphological characteristics of the subpopulations of peripheral blood. In
      agreement with earlier findings, cell total capacitance varied with both cell
      size and plasma membrane folding and the dielectric properties of the NCI-60 cell
      types in suspension reflected the plasma membrane area and volume of the cells at
      their growth sites. Therefore, the behavior of cells in DEP-based manipulations
      is largely determined by their exterior morphological characteristics prior to
      release into suspension. As a consequence, DEP is able to discriminate between
      cells of similar size having different morphological origins, offering a
      significant advantage over size-based filtering for isolating circulating tumor
      cells, for example. The findings provide a framework for anticipating cell
      dielectric behavior on the basis of structure-function relationships and suggest
      that DEP should be widely applicable as a surface marker-independent method for
      sorting cells.

PMID- 23172681
TI  - Attenuation of NDEA-induced hepatocarcinogenesis by naringenin in rats.
AB  - Chemoprevention is one of the most promising and realistic approaches in the
      prevention of cancer. Several bioactive compounds present in fruits and
      vegetables have revealed their cancer curative potential on hepatocellular
      carcinoma. Naringenin is one such naturally occurring flavonoid widely found in
      citrus fruits. In this study, we examined the molecular mechanisms by which
      naringenin inhibited NDEA-induced hepatocellular carcinoma in rats by analysing
      the expression patterns of proliferating cell nuclear antigen, Bcl-2, NF-kappaB,
      VEGF and MMP-2/9. Enhanced cell proliferation and apoptotic evasion in NDEA
      induced hepatocarcinogenesis was associated with imbalance in pro-apoptotic and
      anti-apoptotic proteins together with upregulation of proliferating cell nuclear
      antigen (PCNA) and downregulation of caspase-3. Administration of pretreatment
      and posttreatment of naringenin decreased the expression of PCNA and Bcl-2 and
      increased the expression of Bax and caspase-3, indicating antiproliferative and
      apoptotic effects, respectively. Administration of NDEA increased the tumour
      expression of NF-kappaB, COX-2, VEGF, MMP-2 and MMP-9 that was correlated with
      more aggressive lesions and tumour growth. Downregulation of NF-kappaB, VEGF and
      MMPs by naringenin seen in the present study were correlated with the inhibition
      of liver tumour induced by NDEA. Our results suggest that naringenin could act as
      a legitimate agent by inhibiting cancer processes.

PMID- 23172684
TI  - Effects of alloying element and temperature on the stacking fault energies of
      dilute Ni-base superalloys.
AB  - A systematic study of stacking fault energy (gamma(SF)) resulting from induced
      alias shear deformation has been performed by means of first-principles
      calculations for dilute Ni-base superalloys (Ni(23)X and Ni(71)X) for various
      alloying elements (X) as a function of temperature. Twenty-six alloying elements
      are considered, i.e., Al, Co, Cr, Cu, Fe, Hf, Ir, Mn, Mo, Nb, Os, Pd, Pt, Re, Rh,
      Ru, Sc, Si, Ta, Tc, Ti, V, W, Y, Zn, and Zr. The temperature dependence of
      gamma(SF) is computed using the proposed quasistatic approach based on a
      predicted gamma(SF)-volume-temperature relationship. Besides gamma(SF),
      equilibrium volume and the normalized stacking fault energy (Gamma(SF) =
      gamma(SF)/Gb, with G the shear modulus and b the Burgers vector) are also studied
      as a function of temperature for the 26 alloying elements. The following
      conclusions are obtained: all alloying elements X studied herein decrease the
      gamma(SF) of fcc Ni, approximately the further the alloying element X is from Ni
      on the periodic table, the larger the decrease of gamma(SF) for the dilute Ni-X
      alloy, and roughly the gamma(SF) of Ni-X decreases with increasing equilibrium
      volume. In addition, the values of gamma(SF) for all Ni-X systems decrease with
      increasing temperature (except for Ni-Cr at higher Cr content), and the largest
      decrease is observed for pure Ni. Similar to the case of the shear modulus, the
      variation of gamma(SF) for Ni-X systems due to various alloying elements is
      traceable from the distribution of (magnetization) charge density: the spherical
      distribution of charge density around a Ni atom, especially a smaller sphere,
      results in a lower value of gamma(SF) due to the facility of redistribution of
      charges. Computed stacking fault energies and the related properties are in
      favorable accord with available experimental and theoretical data.

PMID- 23172682
TI  - Non-heritable genetics of human disease: spotlight on post-zygotic genetic
      variation acquired during lifetime.
AB  - The heritability of most common, multifactorial diseases is rather modest and
      known genetic effects account for a small part of it. The remaining portion of
      disease aetiology has been conventionally ascribed to environmental effects, with
      an unknown part being stochastic. This review focuses on recent studies
      highlighting stochastic events of potentially great importance in human disease
      the accumulation of post-zygotic structural aberrations with age in
      phenotypically normal humans. These findings are in agreement with a substantial
      mutational load predicted to occur during lifetime within the human soma. A major
      consequence of these results is that the genetic profile of a single tissue
      collected at one time point should be used with caution as a faithful portrait of
      other tissues from the same subject or the same tissue throughout life. Thus, the
      design of studies in human genetics interrogating a single sample per subject or
      applying lymphoblastoid cell lines may come into question. Sporadic disorders are
      common in medicine. We wish to stress the non-heritable genetic variation as a
      potentially important factor behind the development of sporadic diseases.
      Moreover, associations between post-zygotic mutations, clonal cell expansions and
      their relation to cancer predisposition are central in this context. Post-zygotic
      mutations are amenable to robust examination and are likely to explain a sizable
      part of non-heritable disease causality, which has routinely been thought of as
      synonymous with environmental factors. In view of the widespread accumulation of
      genetic aberrations with age and strong predictions of disease risk from such
      analyses, studies of post-zygotic mutations may be a fruitful approach for
      delineation of variants that are causative for common human disorders.

PMID- 23172683
TI  - Impact of T2 decay on carotid artery wall thickness measurements.
AB  - PURPOSE: To investigate the impact of T2 relaxation of the carotid wall on
      measurements of its thickness. MATERIALS AND METHODS: The common carotid artery
      wall was imaged using a spin echo sequence acquired at four echo times (17 ms to
      68 ms) in 65 participants as part of VALIDATE study. Images were acquired
      transverse to the artery 1.5 cm proximal to the flow divider. Mean wall
      thickness, mean wall signal intensity, lumen area, and outer wall area were
      measured for each echo. Contours were also traced on the image from the fourth
      echo and then propagated to the images from the preceding echoes. This was
      repeated using the image from the first echo. Mean wall signal intensity
      measurements at the four echo times were fit to a mono-exponential decay curve to
      derive the mean T2 relaxation time for each set of contours. RESULTS: Mean wall
      thickness decreased with increasing echo time, with an average thickness
      reduction of 8.6% between images acquired at the first and last echo times (TE)
      (0.93 mm at TE 17 ms versus 0.85 mm at TE 68 ms, P < 0.001). Average T2
      relaxation time of the carotid wall decreased by 3% when the smaller contours
      from the last echo were used, which excluded the outer-most layer (54.3 +/- 7.6
      ms versus 52.7 +/- 6.6 ms, P = 0.03). CONCLUSION: Carotid wall thickness
      measurements decrease with echo time as expected by the fast T2 relaxation time
      of the outer-most layer, namely the adventitia. A short echo time is needed for
      thickness measurements to include adventitia, which plays an important role in
      plaque development.

PMID- 23172685
TI  - HIV Gag-specific immune response mediated by double negative (CD3(+)CD4(-)CD8(-))
      T cells in HIV-exposed seronegative individuals.
AB  - Double negative (DN) T cells are CD3(+), CD4(-), CD8(-) cells with either T-cell
      receptors (TCR) alphabeta or TCR gammadelta whose importance on protection
      against HIV infection is unknown. Since HIV-exposed seronegative individuals
      correspond to an ideal group in whom correlates of protection are expected, the
      role of these cells was studied in 13 HIV-serodiscordant couples in a stable
      relationship and reporting unprotected sexual intercourses. HIV-specific immune
      responses mediated by DN T-cells were evaluated by measuring intracellular
      IFNgamma and MIP1beta (CCL4) production in response to HIV-Gag peptides. Thirty
      five healthy controls not exposed to HIV were tested similarly and used to define
      a threshold for positive responses. Interestingly, Gag-specific DN T-cell
      responses were found in 3/13 (23%) HIV-exposed seronegative individuals (Group
      A), involving both DN/alphabeta(+) and DN/gammadelta(+) T-cells through MIP1beta
      and IFNgamma production. 4/13 (30%) of partners infected with HIV (Group B) also
      showed Gag-specific responses but were mediated exclusively by DN/gammadelta(+) T
      cells, mainly through IFNgamma production. DN T-cells in Group A individuals can
      display differential HIV-specific immune responses, which might contribute to the
      low susceptibility to infection with HIV shown by individuals in Group A.

PMID- 23172686
TI  - Silent information regulator (Sir)T1 inhibits NF-kappaB signaling to maintain
      normal skeletal remodeling.
AB  - Silent information regulator T1 (SirT1) is linked to longevity and negatively
      controls NF-kappaB signaling, a crucial mediator of survival and regulator of
      both osteoclasts and osteoblasts. Here we show that NF-kappaB repression by SirT1
      in both osteoclasts and osteoblasts is necessary for proper bone remodeling and
      may contribute to the mechanisms linking aging and bone loss. Osteoclast- or
      osteoblast-specific SirT1 deletion using the Sirt(flox/flox) mice crossed to
      lysozyme M-cre and the 2.3 kb col1a1-cre transgenic mice, respectively, resulted
      in decreased bone mass caused by increased resorption and reduced bone formation.
      In osteoclasts, lack of SirT1 promoted osteoclastogenesis in vitro and activated
      NF-kappaB by increasing acetylation of Lysine 310. Importantly, this increase in
      osteoclastogenesis was blocked by pharmacological inhibition of NF-kappaB. In
      osteoblasts, decreased SirT1 reduced osteoblast differentiation, which could also
      be rescued by inhibition of NF-kappaB. In further support of the critical role of
      NF-kappaB signaling in bone remodeling, elevated NF-kappaB activity in
      IkappaBalpha(+/-) mice uncoupled bone resorption and formation, leading to
      reduced bone mass. These findings support the notion that SirT1 is a genetic
      determinant of bone mass, acting in a cell-autonomous manner in both osteoblasts
      and osteoclasts, through control of NF-kappaB and bone cell differentiation.

PMID- 23172687
TI  - Arnold Rothstein on Lawrence Friedman.

PMID- 23172688
TI  - Reply from Lawrence Friedman.

PMID- 23172689
TI  - Mild and general conditions for negishi cross-coupling enabled by the use of
      palladacycle precatalysts.
AB  - A wide range of biaryls were synthesized by palladium-catalyzed Negishi cross
      couplings at ambient temperature or with low catalyst loading. This protocol
      features the use of a recently reported aminobiphenyl palladacycle precatalyst to
      generate the catalytically active XPhosPd(0) species. Significantly, a wide range
      of challenging heterocyclic and polyfluorinated aromatic substrates can be
      employed to give products in excellent yields.

PMID- 23172690
TI  - Redo of percutaneous renal denervation in a patient with recurrent resistant
      hypertension after primary treatment success.
AB  - A 79-year-old patient was treated with percutaneous renal denervation (RDN) due
      to resistant arterial hypertension in the summer of 2010. After primary treatment
      success with a decrease of blood pressure from 170/100 to 130/80 mm Hg 6 months
      postablation, the blood pressure rose again at 12 months despite maintenance of
      the pharmacologic regimen and the decision was made to perform a second RDN
      procedure. Three months following the second RDN procedure, blood pressure was
      lowered to 130/77 mm Hg.

PMID- 23172691
TI  - Depicting the semicircular canals with inner-ear MRI: a comparison of the SPACE
      and TrueFISP sequences.
AB  - PURPOSE: To assess the ability of magnetic resonance imaging (MRI) to depict the
      semicircular canals of the inner ear by comparing results from the sampling
      perfection with application-optimized contrasts by using different flip angle
      evolutions (SPACE) sequence with those from the true free induction with steady
      precession (TrueFISP) sequence. MATERIALS AND METHODS: A 1.5-T MRI system was
      used to perform an in vivo study of 10 healthy volunteers and 17 patients. A
      three-point visual score was employed for assessing the depiction of the
      semicircular canals and facial and vestibulocochlear nerves and the contrast-to
      noise ratio (CNR) was computed for the vestibule and pons on images with the
      SPACE and TrueFIPS sequences. RESULTS: There were no susceptibility artifact
      related filling defects with the SPACE sequence. However, the TrueFISP sequence
      showed filling defects for at least one semicircular canal on both sides in seven
      cases for healthy subjects and in 10 cases for patients. The CNR with the SPACE
      sequence was significantly higher than with the TrueFISP sequence (P < 0.05).
      There was no statistically significant difference in depicting the facial and the
      vestibulocochlear nerves (P = 0.32). CONCLUSION: For the depiction of the
      semicircular canal, the SPACE sequence is superior to the TrueFISP sequence.

PMID- 23172693
TI  - Modulation of age-related changes in oxidative stress markers and energy status
      in the rat heart and hippocampus: a significant role for ozone therapy.
AB  - Oxidative stress emerges as a key player in the ageing process. Controlled ozone
      administration is known to promote an oxidative preconditioning or adaptation to
      oxidative stress. The present study investigated whether prophylactic ozone
      administration could interfere with the age-related changes in the heart and the
      hippocampus of rats. Four groups of rats, aged about 3 months old, were used.
      Group 1 (Prophylactic ozone group) received ozone/oxygen mixture by rectal
      insufflations (0.6 mg/kg) twice/week for the first 3 months, then once/week till
      the age of 15 months. Group 2 (Oxygen group) received oxygen as vehicle for ozone
      in a manner similar to group 1. Group 3 (Aged control group) was kept without any
      treatment until the age of 15 months. A fourth group of rats (Adult control
      group) was evaluated at 3 months of age to provide baseline data. Ozone
      alleviated age-associated redox state imbalance as evidenced by reduction of
      lipid and protein oxidation markers, lessening of lipofuscin deposition,
      restoration of glutathione levels in both tissues and normalization of
      glutathione peroxidase activity in the heart tissue. Ozone also mitigated age
      associated energy failure in the heart and the hippocampus, improved cardiac
      cytosolic Ca(2+) homeostasis and restored the attenuated Na(+) , K(+) -ATPase
      activity in the hippocampus of aged rats. These data provide new evidence
      concerning the anti-ageing potential of prophylactic ozone administration.

PMID- 23172694
TI  - First-principles study of ring to cage structural crossover in small ZnO
      clusters.
AB  - Density functional, full-potential computations are performed to study the origin
      and consequences of the ring to cage structural crossover in (ZnO)(n) (n = 2-16)
      clusters. The origin of this structural crossover, which is found to occur at n =
      10, is studied by investigating the behavior of the Zn-O-Zn bond angle, the Zn-O
      bond strength, and the number of bonds in the systems. It is argued that 12 is
      the lowest magic number of ZnO clusters in the ground state, while finite
      temperature vibrational excitations enhance the relative stability of the
      (ZnO)(9) cluster to make it a magic system at temperatures above about 170 K. The
      obtained electronic structure of the clusters before and after applying the many
      body GW corrections evidence a size-induced redshift originating from the ring to
      cage structural crossover in the system. The behavior of the electron density
      bond points of the clusters along with the extrapolated cluster binding energy at
      very large sizes may indicate the existence of a metastable structure for large
      ZnO nanostructures, different from the bulk ZnO structure.

PMID- 23172692
TI  - Disease risk score as a confounder summary method: systematic review and
      recommendations.
AB  - PURPOSE: To systematically examine trends and applications of the disease risk
      score (DRS) as a confounder summary method. METHODS: We completed a systematic
      search of MEDLINE and Web of Science(r) to identify all English language articles
      that applied DRS methods. We tabulated the number of publications by year and
      type (empirical application, methodological contribution, or review paper) and
      summarized methods used in empirical applications overall and by publication year
      (<2000, >=2000). RESULTS: Of 714 unique articles identified, 97 examined DRS
      methods and 86 were empirical applications. We observed a bimodal distribution in
      the number of publications over time, with a peak 1979-1980, and resurgence since
      2000. The majority of applications with methodological detail derived DRS using
      logistic regression (47%), used DRS as a categorical variable in regression
      (93%), and applied DRS in a non-experimental cohort (47%) or case-control (42%)
      study. Few studies examined effect modification by outcome risk (23%).
      CONCLUSION: Use of DRS methods has increased yet remains low. Comparative
      effectiveness research may benefit from more DRS applications, particularly to
      examine effect modification by outcome risk. Standardized terminology may
      facilitate identification, application, and comprehension of DRS methods. More
      research is needed to support the application of DRS methods, particularly in
      case-control studies.

PMID- 23172695
TI  - CE with a boron-doped diamond electrode for trace detection of endocrine
      disruptors in water samples.
AB  - Off-line SPE and CE coupled with electrochemical detection have been used for the
      determination of bisphenol A (BPA), bisphenol F, 4-ethylphenol, and bisphenol A
      diglycidyl ether in bottled drinking water. The use of boron-doped diamond
      electrode as an electrochemical detector in amperometric mode that provides a
      favorable analytical performance for detecting these endocrine-disrupting
      compounds, such as lower noise levels, higher peak resolution with enhanced
      sensitivity, and improved resistance against electrode passivation. The oxidative
      electrochemical detection of the endocrine-disrupting compounds was accomplished
      by boron-doped diamond electrode poised at +1.4 V versus Ag/AgCl without
      electrode pretreatment. An off-line SPE procedure (Bond Elut(r) C18 SPE
      cartridge) was utilized to extract and preconcentrate the compounds prior to
      separation and detection. The minimum concentration detectable for all four
      compounds ranged from 0.01 to 0.06 MUM, having S/N equal to three. After exposing
      the plastic bottle water container under sunlight for 7 days, the estimated
      concentration of BPA in the bottled drinking water was estimated to be 0.03 MUM.
      This proposed approach has great potential for rapid and effective determination
      of BPA content present in water packaging of plastic bottles that have been
      exposed to sunlight for an extended period of time. 

PMID- 23172696
TI  - Amyloidosis in association with spontaneous feline immunodeficiency virus
      infection.
AB  - Tissues from 34 naturally feline immunodeficiency virus (FIV)-infected cats, 13
      asymptomatic cats and 21 cats with signs of feline acquired immunodeficiency
      syndrome (F-AIDS), and 35 FIV-seronegative subjects were examined to determine
      the presence of amyloid deposits. Twenty experimentally FIV-infected cats and
      five specific pathogen-free (SPF) control cats were also included in the study.
      Paraffin-embedded sections from kidney and other organs were submitted to
      histological and histochemical analysis. Amyloid deposits were identified by a
      modified Congo red stain and confirmed by electron microscopy to demonstrate the
      presence of amyloid fibrils in amyloid positive glomeruli. In all positive cases,
      secondary amyloidosis was identified with potassium permanganate pretreatment and
      amyloid type was further characterised by immunohistochemistry using primary
      antibodies against human AA and feline AL amyloids. Amyloid deposits were present
      in different tissues of 12/34 (35%) naturally FIV-infected cats (seven presenting
      F-AIDS and five in asymptomatic phase) and in 1/30 FIV-seronegative cats. All the
      experimentally FIV-infected and SPF subjects showed no amyloid deposits.
      Amyloidosis has been reported in human lentiviral infections, and the data
      reported here demonstrate the need, in naturally FIV-infected cats, to consider
      the presence of amyloidosis in differential diagnosis of hepatic and renal
      disorders to better assess the prognosis of the disease.

PMID- 23172697
TI  - Unilateral uterine segmentary aplasia, papillary endometrial hyperplasia and
      ipsilateral renal agenesis in a cat.
AB  - A 1-year-old, female, previously spayed domestic shorthair cat presented with
      abnormal behavior characterized by rubbing up against objects, vocalization and
      abnormal body posture. A diagnostic laparoscopy was performed and a dilated
      segment of the left uterus and ovary was found in association with ipsilateral
      renal agenesis. Papillary hyperplasia of the endometrium of the dilated segment
      was found on histopathology. The occurrence and findings of this condition are
      reviewed.

PMID- 23172698
TI  - Preliminary results in the redox balance in healthy cats: influence of age and
      gender.
AB  - Oxidative stress (OS) impairs organic function and is considered causally related
      to cellular senescence and death. This study aims to evaluate if the redox
      balance varies in relation to age and gender in healthy cats. To quantify the
      oxidative status of this species we determined the oxidative damage as serum
      reactive oxygen metabolites (ROM) and the total serum antioxidant capacity (SAC).
      In addition, we used the ratio of ROM to SAC as a measure of the oxidative
      balance, with higher values meaning higher oxidative stress (oxidative stress
      index). Our results suggest that the male population is at oxidative risk when
      compared with females, especially between the age of 2 and 7 years. Nutritional
      strategies in this population looking for additional antioxidant support would
      probably avoid the oxidative stress status that predisposes to chronic processes
      in senior male cats. Further clinical trials in this field are recommended.

PMID- 23172700
TI  - Multi-reference-based multiple alignment statistics enables accurate protein
      particle pickup from noisy images.
AB  - Data mining from noisy data/images is one of the most important themes in modern
      science and technology. Statistical image processing is a promising technique for
      analysing such data. Automation of particle pickup from noisy electron
      micrographs is essential, especially when improvement of the resolution of single
      particle analysis requires a huge number of particle images. For such a purpose,
      reference-based matching using primary three-dimensional (3D) model projections
      is mainly adopted. In the matching, however, the highest peaks of the correlation
      may not accurately indicate particles when the image is very noisy. In contrast,
      the density and the heights of the peaks should reflect the probability
      distribution of the particles. To statistically determine the particle positions
      from the peak distributions, we have developed a density-based peak search
      followed by a peak selection based on average peak height, using multi-reference
      alignment (MRA). Its extension, using multi-reference multiple alignment (MRMA),
      was found to enable particle pickup at higher accuracy even from extremely noisy
      images with a signal-to-noise ratio of 0.001. We refer to these new methods as
      stochastic pickup with MRA (MRA-StoPICK) or with MRMA (MRMA-StoPICK). MRMA
      StoPICK has a higher pickup accuracy and furthermore, is almost independent of
      parameter settings. They were successfully applied to cryo-electron micrographs
      of Rice dwarf virus. Because current computational resources and parallel data
      processing environments allow somewhat CPU-intensive MRA-StoPICK and MRMA-StoPICK
      to be performed in a short period, these methods are expected to allow high
      resolution analysis of the 3D structure of particles.

PMID- 23172699
TI  - Obese rats with deficient leptin signaling exhibit heightened sensitivity to
      olfactory food cues.
AB  - The Zucker rat is used as a model of genetic obesity, and while Zucker rats have
      been well studied for their reduced sensitivity to leptin signaling and
      subsequent weight gain, little work has examined their responses to environmental
      signals that are associated with "hedonic" feeding. This study evaluated the
      effects of a high-fat food olfactory cue (bacon) in stimulating nose-poke food
      seeking behavior on first exposure (novel) and after a period of access for
      consumption (familiar) in lean and obese Zucker rats at either 4 or 12 months of
      age, and under ad-lib fed (unrestricted; U) or chronically food-restricted (70%
      of ad-lib; R) conditions. Baseline nose-poke levels were comparable amongst all
      groups. At 4 months of age, only ObU rats displayed increased behavioral
      activation to familiar food cues. Twelve-month-old Ob rats, regardless of diet,
      exhibited substantially greater food-seeking behavior when exposed to both the
      novel and familiar olfactory cues. A strong positive correlation between body
      weight and nose-poke entries for the familiar food cue was observed at both ages,
      while this correlation for the novel food cue was significant in 12-month-old
      rats only. Similarly, there were strong positive correlations between food intake
      and poke entries for the familiar food cue was observed at both ages, while this
      correlation for the novel food cue was significant in 12-month-old rats only.
      Although it is possible that differences in olfactory sensitivity contribute to
      these behavioral effects, our findings support the interactions between food
      intake, obesity, and food-seeking behavior and are consistent with leptin
      inhibiting the brain's reactivity to food cues and suggest that the enhanced
      sensitivity to the food cues with leptin deficiency is likely to contribute to
      overeating and weight gain.

PMID- 23172701
TI  - Transient heating of expressed breast milk up to 65 degrees C inactivates HIV-1
      in milk: a simple, rapid, and cost-effective method to prevent postnatal
      transmission.
AB  - The postnatal transmission of human immunodeficiency virus (HIV) from mothers to
      children occurs through breastfeeding. Although heat treatment of expressed
      breast milk is a promising approach to make breastfeeding safer, it is still not
      popular, mainly because the recommended procedures are difficult to follow, or
      time-consuming, or because mothers do not know which temperature is sufficient to
      inactivate HIV without destroying the nutritional elements of milk. To overcome
      these drawbacks, a simple and rapid method of heat treatment that a mother could
      perform with regular household materials applying her day-to-day art of cooking
      was examined. This structured experiment has demonstrated that both cell-free and
      cell-associated HIV type 1 (HIV-1) in expressed breast milk could be inactivated
      once the temperature of milk reached 65 degrees C. Furthermore, a heating method
      as simple as heating the milk in a pan over a stove to 65 degrees C inhibited HIV
      1 transmission retaining milk's nutritional key elements, for example, total
      protein, IgG, IgA, and vitamin B(12) . This study has highlighted a simple,
      handy, and cost-effective method of heat treatment of expressed breast milk that
      mothers infected with HIV could apply easily and with more confidence.

PMID- 23172702
TI  - Fast subset scan for multivariate event detection.
AB  - We present new subset scan methods for multivariate event detection in massive
      space-time datasets. We extend the recently proposed 'fast subset scan' framework
      from univariate to multivariate data, enabling computationally efficient
      detection of irregular space-time clusters even when the numbers of spatial
      locations and data streams are large. For two variants of the multivariate subset
      scan, we demonstrate that the scan statistic can be efficiently optimized over
      proximity-constrained subsets of locations and over all subsets of the monitored
      data streams, enabling timely detection of emerging events and accurate
      characterization of the affected locations and streams. Using our new fast search
      algorithms, we perform an empirical comparison of the Subset Aggregation and
      Kulldorff multivariate subset scans on synthetic data and real-world disease
      surveillance tasks, demonstrating tradeoffs between the detection and
      characterization performance of the two methods.

PMID- 23172704
TI  - Loss of pace capture after radiofrequency application predicts the formation of
      uniform transmural lesions.
AB  - AIMS: Lesion transmurality is critical to procedural success in radiofrequency
      catheter ablation. We sought to determine whether loss of pace capture (PC) with
      high-output unipolar and/or bipolar pacing predicts the formation of uniform
      transmural lesions. METHODS AND RESULTS: Ten juvenile swine were anaesthetized
      and prepped under sterile conditions. Seventy-seven isolated radiofrequency
      applications (RFAs) using a 3.5 mm tip-irrigated catheter were available for
      analysis. Pace capture was assessed before and after RFA at 10 mA/2 ms and
      catheter stability verified with a three-dimensional mapping system. Pace capture
      was defined as 1 : 1 or intermittent local capture per paced beat. Myocardial
      contact and catheter orientation were assessed using intracardiac echo.
      Endocardial and epicardial lesion areas were measured after sacrifice using 2,3,5
      triphenyltetrazolium chloride staining. A uniform transmural lesion was defined
      as an epicardial-to-endocardial surface ratio (epi/endo) >= 76%. Seventy-four per
      cent of lesions were transmural and 55.8% of lesions had an epi/endo ratio >=
      76%. In all, 79.2% of lesions associated with loss of bipolar PC were uniform
      whereas 20.8% of lesions with loss of bipolar PC were non-uniform (P = 0.006).
      Loss of bipolar PC was associated with higher mean epicardial/endocardial ratio
      compared with lesions with persistent PC (P = 0.019). Echocardiographic evidence
      of optimal catheter contact during RFA improved the predictive accuracy of
      uniform lesion formation when loss of bipolar PC was noted after RFA. CONCLUSION:
      Loss of bipolar PC after RFA is associated with the formation of uniform lesions
      in atrial tissue. Optimal catheter contact further improves the predictive
      accuracy associated with loss of PC.

PMID- 23172703
TI  - Rhodium(III)-catalyzed alkenyl C-H bond functionalization: convergent synthesis
      of furans and pyrroles.
AB  - Ring in the new: a new annulation for the efficient synthesis of substituted
      furans and pyrroles is reported. The Rh(III) -catalyzed reaction of O-methyl
      alpha,beta-unsaturated oximes with aldehydes and N-tosyl imines affords secondary
      alcohol and amine intermediates, respectively. Cyclization and aromatization
      occurs under the reaction conditions to provide access to biologically relevant
      furans and pyrroles in good yields. Cp*=C(5)Me(5), DCE=1,2-dichloroethane,
      THF=tetrahydrofuran.

PMID- 23172705
TI  - Pseudo T-wave variations on internal loop recorder: predictor or confounder?

PMID- 23172706
TI  - Closure of tubular patent ductus arteriosus in infants with the Amplatzer
      Vascular Plug II.
AB  - OBJECTIVES: We used the Amplatzer Vascular Plug II to close tubular patent ductus
      arteriosus (DA) in infants. BACKGROUND: Despite advancements in device design,
      catheter-based therapy for the DA of tubular morphology has been problematic.
      Likewise, the currently available devices are not designed to close DAs in small,
      often premature infants as the size of the delivery systems can be prohibitive
      and the devices obstructive to aortic or pulmonary artery flow. METHODS: We
      report our experience using the second-generation Amplatzer Vascular Plug (AVP
      II) in 10 patients with sizeable, tubular DAs, seven of whom were less than or
      equal to 4.0 kg. RESULTS: Complete closure was attained in all patients, with one
      minor complication. In four small infants, the device was delivered without
      arterial access under echocardiographic guidance. CONCLUSION: It is our belief
      that the AVP II device can be a useful embolization device for DAs in this
      difficult patient population.

PMID- 23172707
TI  - Health risk behaviors associated with agrochemical exposure among rice farmers in
      a rural community, Thailand: a community-based ethnography.
AB  - The study objective was to evaluate health beliefs and behaviors associated with
      agrochemical exposure among rice farmers. We applied the Health Belief Model,
      community-based ethnography, and public health risk assessment for this study.
      Data were collected from 101 rice farmers in Khlong Seven community between
      January and June 2010. Data comprised observations, unstructured and
      semistructured interviews, and focus group discussions. We showed that farmers
      had moderate levels of perceived susceptibility to, severity of, benefits of, and
      barriers to using agrochemicals safely. The major risk factors related to
      agrochemical exposure resulted from the misuse of pesticides, including erroneous
      beliefs of farmers regarding pesticide toxicity, the use of faulty spraying
      equipment, the lack of proper maintenance of spraying equipment, or the lack of
      protective gear and appropriate clothing. An intervention program is necessary to
      improve safety with regard to agrochemicals in the rice Khlong Seven community.

PMID- 23172708
TI  - A role for PKCdelta in foam cell formation?

PMID- 23172709
TI  - A role for PKCdelta in foam cell formation: reply.

PMID- 23172710
TI  - Signalling between G-protein-coupled receptors and TASK1 channels.

PMID- 23172712
TI  - First-principles calculation of structural, mechanical, magnetic and
      thermodynamic properties for gamma-M23C6 (M = Fe, Cr) compounds.
AB  - We report the results of our first-principles calculations of structural
      stability, mechanical, magnetic, and thermodynamic properties for gamma-M(23)C(6)
      (M = Fe, Cr) compounds with each of the four metal Wyckoff sites being occupied
      in turn by Fe. The thermodynamic properties and the temperature dependence of the
      mechanical behavior of gamma-M(23)C(6) compounds are investigated based on the
      quasi-harmonic Debye model. The results show that the thermodynamic properties of
      gamma-M(23)C(6) (M = Fe, Cr) compounds are more dependent on the position of Fe
      atoms than the amount of Fe.

PMID- 23172711
TI  - Pulmonary vein morphology by free-breathing whole heart magnetic resonance
      imaging at 3 Tesla versus breathhold multi-detector computed tomography.
AB  - PURPOSE: To compare pulmonary vein and left atrial anatomy using three
      dimensional free-breathing whole-heart magnetic resonance imaging (MR) at 3 Tesla
      (T) and multi-detector computed tomography (MDCT). MATERIALS AND METHODS: Thirty
      three subjects (19 male, age 49 +/- 12 years) underwent free-breathing 3T MR and
      contrast-enhanced MDCT during inspiratory breath hold. Pulmonary vein parameters
      (ostial areas, diameters, angles) were measured. RESULTS: All pulmonary veins and
      anomalies were identified by 3T MR and by MDCT. The right-sided pulmonary veins
      were directed more posteriorly, the right superior pulmonary vein more
      inferiorly, and the right inferior pulmonary vein more superiorly by 3T MR when
      compared with MDCT. The cross-sectional area, perimeters and minimum diameters of
      right-sided pulmonary vein ostia were significantly larger by MR, as were the
      maximum diameters of right and left inferior pulmonary veins. There were no
      significant differences between techniques in distance to first pulmonary vein
      branch. CONCLUSION: Pulmonary vein measurements demonstrated significant
      differences in angulations and dimensions when 3T MR is compared with MDCT. These
      differences likely represent hemodynamic and respiratory variation during free
      breathing with MR versus breath-holding with MDCT. MR imaging at 3T during free
      breathing offers an alternate method to define pulmonary vein and left atrial
      anatomy without exposure to radiation.

PMID- 23172713
TI  - Expression of FGF4 mRNA is mediated by mating behaviours in mice.
AB  - In mammals, breeding is preceded by species-specific mating behaviours. In this
      study, we investigated whether parthenogenetic embryo quality could be improved
      by mating behaviours in mice. To investigate this hypothesis, female mice were
      mated with vasectomized Kunming white male mice after superovulation. Oocytes
      were collected and counted at 16 h after superovulation. The oocytes were then
      artificially activated by medium containing 10 mM strontium chloride and 5 ug/ml
      cytochalasin B. Blastocysts were obtained by cultivating activated oocytes in
      vitro. Expression levels of reprogramming transcription factors (i.e. Oct4, Sox2,
      Klf4 and c-Myc) in oocytes, apoptosis-related genes (i.e. Bax, Bcl2 and c-Myc) in
      cumulus cells and pluripotency-related transcription factors (i.e. Oct4, Nanog
      and FGF4) in blastocysts were analysed in samples collected from mated and
      unmated mice. Additionally, developmental competence of parthenogenetic embryos
      was used to assess following fibroblast growth factor 4 (FGF4) treatment. The
      results showed that the formation rate of blastocysts in unmated mice was
      significantly higher than that in mated mice (p < 0.05). Embryo development was
      primarily blocked at the eight-cell stage in mated mice; however, the blastocyst
      formation rate did not differ significantly between groups after the addition of
      25 ng/ml FGF4 to the medium at the four-cell stage (p > 0.05). Moreover, the
      expression of the reprogramming factor Sox2 was significantly different in
      oocytes collected from mated versus unmated mice. Taken together, our results
      demonstrated that mating behaviours influenced embryonic development in vitro by
      decreasing FGF4 expression.

PMID- 23172714
TI  - Factors associated with spontaneous reporting of adverse drug reactions in Japan.
AB  - PURPOSE: Spontaneous reported adverse drug reactions (ADRs) are currently the
      main source of pharmacovigilance activities in each country. The number of ADRs
      reported to the authority warns of safety risks to patients, but it also reflects
      the efficiency and limitations of the reporting system itself. This article
      explored how the accumulation of safety information, status in foreign countries
      (e.g., US approval), drug company attributes, and regulatory actions (e.g., early
      post-marketing phase vigilance; EPPV) were associated with the numbers of
      spontaneously reported ADRs in Japan. METHODS: All serious ADRs for drugs for
      which the active ingredients or route of administration were approved in Japan
      from 2000 through 2005 were collected from the national database. The numbers of
      serious ADRs within the first 2 and 3 years after launch were analyzed using the
      negative binominal distribution model. RESULTS: The launch lag and the presence
      of drugs with a similar mode of action were negatively associated with the ADR
      numbers, but the number of study subjects for the new drug application (NDA)
      showed no clear association. The number of sales representatives and the
      implementation of EPPV were positively associated with the ADR numbers.
      CONCLUSION: The accumulation of foreign post-market evidence seemed to be more
      important for drug safety in Japan than was the amount of pre-approval safety
      data. The positive impacts of sales representatives and EPPV suggested a critical
      role for drug companies in drug safety and also the importance of considering how
      best to collect information in local situations with unique regulatory
      requirements.

PMID- 23172715
TI  - Nanoscale block copolymer ordering induced by visible interferometric
      micropatterning: a route towards large scale block copolymer 2D crystals.
AB  - We have overcome the cost and time consumption limitations of common lithography
      techniques used to control the self-assembly of block copolymers into highly
      ordered 2D arrays through the use of a guiding pattern created from a polymeric
      sub-layer. The guiding pattern is a sinusoidal surface-relief grating
      interferometrically inscribed onto an azobenzene containing copolymer sub-layer
      leading to a defect-free single grain of block copolymer domains.

PMID- 23172716
TI  - Comparing diagnostic tests: trials in people with discordant test results.
AB  - Diagnostic tests are traditionally compared for accuracy against a gold standard
      but can also be compared prospectively in a trial. A conventional trial comparing
      two tests would randomize each participant to a testing strategy, but a more
      efficient alternative is to give both tests to all participants and follow up
      those with discordant results. Participants could be randomized before or after
      testing. The statistical analysis of such a trial has not previously been
      described. We investigated two estimates of the risk difference for a binary
      outcome: one based on analysing outcomes as if from a conventional trial and one
      combining estimates of different parameters in the manner of a decision analysis.
      We show that the trial estimate and decision analysis estimate are both unbiased
      and derive approximate formulae for their standard errors. By using the decision
      analysis estimate (but not the trial estimate), the same precision can be
      achieved by randomizing before testing as by randomizing after. To avoid
      destroying equipoise, and to allow consenting and randomizing to be carried out
      at the same visit, we recommend randomizing before testing. Giving both tests to
      all participants means fewer need to be recruited: in one example from the
      literature, the proposed design was nearly four times more efficient in this
      sense than a conventional trial design.

PMID- 23172718
TI  - Measurable spin-polarized current in two-dimensional topological insulators.
AB  - We propose a simple method for generating a spin-polarized current in a two
      dimensional topological insulator. As z-component magnetic impurities exist on
      one edge of the Kane-Mele model, a subgap is opened in the corresponding pair of
      edge states, but another pair of gapless edge states is still protected by the
      time reversal symmetry. Thus the conductance plateau with the value e(2)/h in the
      subgap corresponds to a single-edge and spin-polarized current. We also find that
      the spin-polarized current is insensitive to weak non-magnetic disorder. This
      mechanism for generating spin-polarized currents is independent of the concrete
      theoretical model and can be generalized to two-dimensional topological
      insulators, such as HgTe/CdTe quantum wells and silicene nanoribbons.

PMID- 23172717
TI  - Cascade approach to stereoselective polycyclic ether formation: epoxides as
      trapping agents in the transposition of allylic alcohols.
AB  - Complexity from simplicity: polycyclic ethers are synthesized by cascade
      reactions involving the use of epoxides as electrophilic traps in the
      transposition of allylic alcohols. Stereogenic centers are created by
      functionalizing prochiral sites under thermodynamic control, and remote
      stereoinduction can be achieved through the use of ketones as conduits.

PMID- 23172719
TI  - Automatic model-based analysis of skeletal muscle BOLD-MRI in reactive hyperemia.
AB  - PURPOSE: To propose a quantitative model for a reliable and operator independent
      estimation of parameters describing blood oxygen-level dependent (BOLD) MRI time
      course in calf muscles during reactive hyperemia. MATERIALS AND METHODS: Echo
      planar imaging-based BOLD-MRI of the human calf were acquired during and after
      cuff-induced ischemia of the leg. Regions of interest were drawn in soleus,
      gastrocnemius and tibialis anterior muscles. A gamma-variate plus a sigmoidal
      function were fitted to the reactive hyperemia time courses and parameters
      including time to peak (TTP), hyperemic peak value (HPV), peak area, and peak
      width were calculated. In addition, the TTP and HPV parameters were estimated
      manually by two operators to validate the reliability of the fitting procedure.
      RESULTS: The model function was fitted successfully to all data with a minimum
      reduced R(2) around 0.9. The in vivo results were in agreement with manually
      determined values (r >= 0.69), although significant inter-operator differences
      were observed. CONCLUSION: The proposed method allows for rapid, operator
      independent and robust quantification of muscle BOLD signal during reactive
      hyperemia. The model worked equally well over a wide range of imaging parameters
      and data quality. This approach should contribute significantly to the
      standardization of skeletal muscle BOLD-MRI, an important step toward its
      clinical application.

PMID- 23172720
TI  - Comparison of large-area position-sensitive solid-state photomultipliers for
      small animal PET.
AB  - This paper evaluates the performance of two large-area position-sensitive solid
      state photomultipliers (PS-SSPM) for use in small animal PET detector designs.
      Both PS-SSPM device designs are 1 cm2 in area, the first being a 2 * 2 tiled
      array of 5 mm * 5 mm PS-SSPMs and the second being a 10 mm * 10 mm continuous PS
      SSPM. Signal-to-noise measurements were performed to investigate the optimal
      operating parameters for each device and to compare the performance of the two PS
      SSPM designs. A maximum signal-to-noise ratio of 29.3 was measured for the 5 mm
      PS-SSPM array and 15.1 for the 10 mm PS-SSPM, both measurements were made at 0 
      degrees C and at the optimal bias voltage. The best energy resolution measured
      with an array of 1.3 mm polished LSO crystals was 16% for the 5 mm PS-SSPM array
      and 18% for the 10 mm PS-SSPM. The timing properties of both devices were
      similar, with a best timing resolution (in coincidence with an LSO/PMT detector)
      of 6.8 ns (range 6.8-8.9 ns) and 7.1 ns (range 7.1-9.6 ns) for the 5 mm PS-SSPM
      and 10 mm PS-SSPM respectively. The 2 * 2 array of 5 mm PS-SSPMs was able to
      visually resolve the elements in an 0.5 * 0.5 * 20 mm LYSO scintillator array
      (unpolished, diffuse reflector) with an average peak-to-valley ratio in the flood
      histograms of ~11 indicating clear separation of the crystals. Advantages and
      drawbacks of PET detector designs using PS-SSPM photodetectors are addressed and
      comparisons to other small-animal PET detector designs using position-sensitive
      avalanche photodiodes are made.

PMID- 23172721
TI  - Very late erosion of Amplatzer septal occluder device presenting as pericardial
      pain and effusion 8 years after placement.
AB  - We report the case of a very late erosion of an Amplatzer septal occluder (ASO)
      device more than 8 years after implant, presenting without signs of cardiac
      tamponade. To date, this case represents the longest period between ASO device
      implantation and clinical presentation following erosion. The overall rate of
      device erosion remains low, and the majority reported so far has occurred early,
      but clinicians should remain alert to the possibility of very late erosion in
      patients with ASO devices.

PMID- 23172722
TI  - Twisting carbon nanotube fibers for both wire-shaped micro-supercapacitor and
      micro-battery.

PMID- 23172723
TI  - TPH gene polymorphisms are associated with disease perception and quality of life
      in women with irritable bowel syndrome.
AB  - The aims of this exploratory study were to examine whether tryptophan hydroxylase
      (TPH) gene polymorphisms are associated with psychosocial factors in women with
      irritable bowel syndrome (IBS). TPH is the rate-limiting enzyme in the
      biosynthesis of serotonin and has two isoforms, TPH1 and TPH2. Four single
      nucleotide polymorphisms (SNPs) in the TPH1 gene and one SNP in the TPH2 gene
      were selected based on previous studies investigating associations between these
      SNPs and psychiatric or behavioral disorders. One hundred ninety-nine Caucasian
      women with IBS were included. Results of univariate analysis showed no
      association between TPH1and TPH2 gene SNPs and current level of psychological
      distress or psychiatric illness. However, TPH1 gene SNPs were associated with IBS
      related cognitions (rs4537731 and rs21105) and quality of life (rs684302 and
      rs1800532), in particular the mental health and energy subscales. These
      associations were independent of the subjects' levels of gastrointestinal
      symptoms. These results suggest that patients' perception of their illness, and
      of the impact it has on their lives, may be subject to genetic influences, in
      this case sequence variants in TPH1. However, caution should be used in
      interpreting these results given the large number of hypothesis tests performed
      in this exploratory hypothesis-generating study, and the results should be
      considered tentative until confirmed in an independent sample. 

PMID- 23172724
TI  - Sample size estimation in educational intervention trials with subgroup
      heterogeneity in only one arm.
AB  - We present closed form sample size and power formulas motivated by the study of a
      psycho-social intervention in which the experimental group has the intervention
      delivered in teaching subgroups whereas the control group receives usual care.
      This situation is different from the usual clustered randomized trial because
      subgroup heterogeneity only exists in one arm. We take this modification into
      consideration and present formulas for the situation in which we compare a
      continuous outcome at both a single point in time and longitudinally over time.
      In addition, we present the optimal combination of parameters such as the number
      of subgroups and number of time points for minimizing sample size and maximizing
      power subject to constraints such as the maximum number of measurements that can
      be taken (i.e., a proxy for cost).

PMID- 23172725
TI  - Studying the fragmentation behavior of peptides with arginine phosphorylation and
      its influence on phospho-site localization.
AB  - Phospho-proteomic studies opened a broad view onto the main mechanisms of
      regulating cellular processes. Our recent discovery of a protein arginine kinase
      and its target in bacteria added a previously undescribed type of phosphorylation
      to control protein activity. Several challenges arise from large in vivo studies
      of this and other types of phosphorylations. The main factors impeding correct
      localization are low spectral quality, neutral loss of phosphoric acid, and gas
      phase rearrangements, which have recently been described for phospho-serine, 
      threonine, and -tyrosine. Studies on histidine-phosphorylated peptides, a
      nitrogen-bound phosphorylation, also reported loss of phosphoric acid upon
      collision-induced dissociation. We were interested in studying the behaviour of
      arginine phosphorylation under different fragmentation conditions and its
      influence on site localization. First, we determined the percentage of false
      localizations obtained by three different search engines and a software tool
      dedicated for phospho-site determination. Next, we demonstrate that application
      of collisional activation for analysis of arginine-phosphorylated peptides leads
      to extensive elimination of phosphoric acid and increases the numbers of false
      localizations, while the modification is maintained on the arginine side chain
      upon electron-transfer dissociation. Furthermore, we also observed a
      rearrangement of the phosphorylation onto serine and glutamic acid side chains
      upon collisional activation.

PMID- 23172726
TI  - Comparison of splicing factor 3b inhibitors in human cells.
AB  - Name your splice: FR901464 analogues and herboxidiene inhibit constitutive
      splicing, most likely by inhibiting spliceosomal subunit SF3b. A parallel
      comparison of these compounds in a cell-based assay system showed meayamycin B as
      the most potent splicing inhibitor among these small molecules.

PMID- 23172728
TI  - Genome damage in induced pluripotent stem cells: assessing the mechanisms and
      their consequences.
AB  - In 2006, Shinya Yamanaka and colleagues discovered how to reprogram terminally
      differentiated somatic cells to a pluripotent stem cell state. The resulting
      induced pluripotent stem cells (iPSCs) made a paradigm shift in the field,
      further nailing down the disproval of the long-held dogma that differentiation is
      unidirectional. The prospect of using iPSCs for patient-specific cell-based
      therapies has been enticing. This promise, however, has been questioned in the
      last two years as several studies demonstrated intrinsic epigenetic and genomic
      anomalies in these cells. Here, we not only review the recent critical studies
      addressing the genome integrity during the reprogramming process, but speculate
      about the underlying mechanisms that could create de novo genome damage in iPSCs.
      Finally, we discuss how much an elevated mutation load really matters considering
      the safety of future therapies with cells heavily cultured in vitro.

PMID- 23172727
TI  - Tissue-specific responses to aberrant FGF signaling in complex head phenotypes.
AB  - BACKGROUND: The role of fibroblast growth factor and receptor (FGF/FGFR)
      signaling in bone development is well studied, partly because mutations in FGFRs
      cause human diseases of achondroplasia and FGFR-related craniosynostosis
      syndromes including Crouzon syndrome. The FGFR2c C342Y mutation is a frequent
      cause of Crouzon syndrome, characterized by premature cranial vault suture
      closure, midfacial deficiency, and neurocranial dysmorphology. Here, using
      newborn Fgfr2c(C342Y/+) Crouzon syndrome mice, we tested whether the phenotypic
      effects of this mutation go beyond the skeletal tissues of the skull, altering
      the development of other non-skeletal head tissues including the brain, the eyes,
      the nasopharynx, and the inner ears. RESULTS: Quantitative analysis of 3D
      multimodal imaging (high-resolution micro-computed tomography and magnetic
      resonance microscopy) revealed local differences in skull morphology and coronal
      suture patency between Fgfr2c(C342Y/+) mice and unaffected littermates, as well
      as changes in brain shape but not brain size, significant reductions in
      nasopharyngeal and eye volumes, and no difference in inner ear volume in
      Fgfr2c(C342Y/+) mice. CONCLUSIONS: These findings provide an expanded catalogue
      of clinical phenotypes in Crouzon syndrome caused by aberrant FGF/FGFR signaling
      and evidence of the broad role for FGF/FGFR signaling in development and
      evolution of the vertebrate head.

PMID- 23172730
TI  - All conjugated copolymer excitonic multiferroics.
AB  - A substantial magnetoelectric coupling effect of an excitonic all-conjugated
      block copolymer multiferroics consisting of electronically distinct polythiophene
      derivatives is reported. The observations open new avenues for the
      multifunctional all-conjugated block copolymer synthesis and electric field
      tunable multiferroic devices.

PMID- 23172729
TI  - Long-term results of plaque excision combined with aggressive pharmacotherapy in
      high-risk patients with advanced peripheral artery disease (SAVE a LEG registry).
AB  - BACKGROUND: In United States alone there are more than 12 million people with
      peripheral artery disease (PAD). Long-term outcomes of plaque excision in high
      risk population (patients with diabetes and patients with end stage renal disease
      on dialysis) are scarce. METHODS: Since November 2003, we treated 225 consecutive
      patients (138 male, mean age: 66.3 +/- 12.4, range: 29-93) with SilverHawk(TM)
      plaque excision for critical limb ischemia or disabling claudication. A total of
      367 procedures were performed treating 832 lesions (157 restenotic, 675 de novo).
      One hundred fifty-five patients (68.9%) were diabetics, 74 (32.9%) were on
      dialysis. All patients were treated with statins, clopidogrel, aspirin, and
      aggressive glycemic control. The primary endpoint for our study was target lesion
      revascularization (TLR), and the secondary endpoint was an assessment of major
      adverse events (all cause death, amputation, TLR). RESULTS: The average time of
      observation was 2.2 +/- 1.2 years. Procedural success rate was 99.4% with <30%
      residual stenosis achieved in 818 (98.9%) lesions. SilverHawk was used alone in
      86.7%. No acute limb loss or major perforation occurred. Sixty (26.6%) patients
      had TLR. Long-term mortality was 16.4%. Seven (3.1%) patients had to undergo
      major amputations and 7 (3.1%) minor amputations. Seventy (31.1%) patients had a
      major adverse event. Atorvastatin 80 mg was found to be independent predictor of
      survival, and major amputation was found to be independent predictor of
      mortality. CONCLUSIONS: SilverHawk Plaque Excision combined with aggressive
      pharmacotherapy in this presented high-risk population is associated with
      promising long-term outcomes that compare favorably with accepted standards of
      care.

PMID- 23172731
TI  - Usefulness of Gd-EOB-DTPA-enhanced MR imaging in the evaluation of simple
      steatosis and nonalcoholic steatohepatitis.
AB  - PURPOSE: To evaluate the usefulness of gadolinium ethoxybenzyl
      diethylenetriaminepentaacetic acid (Gd-EOB-DTPA)-enhanced MR imaging (EOB-MRI) in
      differentiating between simple steatosis and nonalcoholic steatohepatitis (NASH),
      as compared with MR in-phase/out-of-phase imaging. The correlations between the
      MR features and histological characteristics were preliminarily investigated.
      MATERIALS AND METHODS: From April 2008 to October 2011, 25 patients (13 simple
      steatosis and 12 NASH) who underwent both EOB-MRI and in-phase/out-of-phase
      imaging were analyzed. The hepatobiliary-phase enhancement ratio and signal
      intensity loss on opposed-phase T1-weighted images (fat fraction) were compared
      between the simple steatosis and NASH groups. In the simple steatosis and NASH
      groups, the correlations between enhancement ratio and histological grade/stage
      were explored. In the NASH group, fat fraction was correlated with the steatosis
      score. RESULTS: The enhancement ratio in NASH was significantly lower than that
      in simple steatosis (P = 0.03). In the simple steatosis and NASH groups, the
      enhancement ratio was significantly correlated with the fibrosis stage (r = 
      0.469, P = 0.018). Fat fraction in NASH was strongly correlated with the
      steatosis score (r = 0.728, P = 0.007). CONCLUSION: In simple steatosis and NASH,
      the hepatobiliary-phase enhancement ratio of EOB-MRI showed significant
      association with fibrosis stage, and may be a useful discriminating parameter
      compared with the fat fraction measured by in-phase/out-of-phase imaging.

PMID- 23172733
TI  - Social epidemiology and health economics: the need to find common grounds.

PMID- 23172732
TI  - Family and home influences on children's after-school and weekend physical
      activity.
AB  - BACKGROUND: Family- and home-related factors have been shown to be associated
      with children's physical activity (PA), but may be time-dependent. Here we
      investigate whether family- and home-related correlates of children's PA are
      different for the after-school period on weekdays than for the weekend. METHODS:
      Data on 21 family- and home-related variables and objectively measured PA
      (Actigraph GT1M) were available from 1608 Year 5 children (9-10 years old) from
      92 schools in Norfolk participating in the SPEEDY (Sport, Physical activity and
      Eating behaviour: Environmental Determinants in Young people) study. Multi-level
      multiple linear regression was used to quantify cross-sectional associations
      between the family/home variables and average min per day of moderate-to-vigorous
      PA (MVPA, >=2000 counts/min) after school on weekdays and at the weekend. Models
      were additionally adjusted for age, sex, BMI z-score and registered accelerometer
      wear time. RESULTS: After-school MVPA was associated with parent education (beta:
      -1.1; 95% CI -2.0 to -0.2), being allowed to play out in the neighbourhood (beta:
      1.3; 0.7-1.8), restrictions on walking/cycling to friends' houses (beta: -1.1; 
      1.6 to -0.7), restrictions on sedentary behaviour (beta: -0.3; -0.5 to -0.02) and
      family social support (beta: 1.0; 0.7-1.3). Weekend MVPA was associated with
      number of siblings (beta: 2.6; 0.5-4.8), family encouragement (beta: 1.1; 0.2
      2.0) and family social support (beta: 1.5; 0.5-2.5). CONCLUSION: Family social
      support is positively associated with children's out-of-school PA both at
      weekdays and in weekends. However, rules and restrictions appear to be important
      only on weekdays. The results of this study merit consideration when identifying
      appropriate timing of PA-promotion strategies.

PMID- 23172734
TI  - Contaminant-mobilizing capability of fullerene nanoparticles (nC60): Effect of
      solvent-exchange process in nC60 formation.
AB  - Fullerene nanoparticles (nC(60)) in aqueous environments can significantly
      enhance the transport of hydrophobic organic contaminants by serving as a
      contaminant carrier. In the present study, the authors examine the effect of the
      solvent-exchange process on nC(60) aggregate formation and, subsequently, on
      nC(60) 's contaminant-mobilizing capability. A series of nC(60) samples were
      prepared using a modified toluene-water solvent-exchange method through the
      inclusion of a secondary organic solvent in the phase transfer of molecular C(60)
      in toluene to nC(60) in water. Two groups of solvents--a water-miscible group and
      a non-water-miscible group-of varied polarity were selected as secondary
      solvents. The involvement of a secondary solvent in the phase transfer process
      had only small effects on the particle size and distribution, zeta potential, and
      mobility of the nC(60) products but significantly influenced the capability of
      nC(60) to enhance the transport of 2,2',5,5'-polychlorinated biphenyl (PCB) in a
      saturated sandy soil column, regardless of whether the secondary solvent was
      water-miscible or non-water-miscible. The two groups of secondary solvents appear
      to affect the aggregation properties of nC(60) in water via different mechanisms.
      In general, nC(60) products made with a secondary water-miscible solvent have
      stronger capabilities to enhance PCB transport. Taken together, the results
      indicate that according to formation conditions and solvent constituents, nC(60)
      will vary significantly in its interactions with organic contaminants,
      specifically as related to adsorption or desorption as well as transport in
      porous media.

PMID- 23172736
TI  - Bayesian nonparametric variable selection as an exploratory tool for discovering
      differentially expressed genes.
AB  - High-throughput scientific studies involving no clear a priori hypothesis are
      common. For example, a large-scale genomic study of a disease may examine
      thousands of genes without hypothesizing that any specific gene is responsible
      for the disease. In these studies, the objective is to explore a large number of
      possible factors (e.g., genes) in order to identify a small number that will be
      considered in follow-up studies that tend to be more thorough and on smaller
      scales. A simple, hierarchical, linear regression model with random coefficients
      is assumed for case-control data that correspond to each gene. The specific model
      used will be seen to be related to a standard Bayesian variable selection model.
      Relatively large regression coefficients correspond to potential differences in
      responses for cases versus controls and thus to genes that might 'matter'. For
      large-scale studies, and using a Dirichlet process mixture model for the
      regression coefficients, we are able to find clusters of regression effects of
      genes with increasing potential effect or 'relevance', in relation to the outcome
      of interest. One cluster will always correspond to genes whose coefficients are
      in a neighborhood that is relatively close to zero and will be deemed least
      relevant. Other clusters will correspond to increasing magnitudes of the
      random/latent regression coefficients. Using simulated data, we demonstrate that
      our approach could be quite effective in finding relevant genes compared with
      several alternative methods. We apply our model to two large-scale studies. The
      first study involves transcriptome analysis of infection by human
      cytomegalovirus. The second study's objective is to identify differentially
      expressed genes between two types of leukemia.

PMID- 23172735
TI  - Evaluation of exogenous siRNA addition as a metabolic engineering tool for
      modifying biopharmaceuticals.
AB  - Traditional metabolic engineering approaches, including homologous recombination,
      zinc-finger nucleases, and short hairpin RNA, have previously been used to
      generate biologics with specific characteristics that improve efficacy, potency,
      and safety. An alternative approach is to exogenously add soluble small
      interfering RNA (siRNA) duplexes, formulated with a cationic lipid, directly to
      cells grown in shake flasks or bioreactors. This approach has the following
      potential advantages: no cell line development required, ability to tailor mRNA
      silencing by adjusting siRNA concentration, simultaneous silencing of multiple
      target genes, and potential temporal control of down regulation of target gene
      expression. In this study, we demonstrate proof of concept of the siRNA feeding
      approach as a metabolic engineering tool in the context of increasing monoclonal
      antibody (MAb) afucosylation. First, potent siRNA duplexes targeting fut8 and
      gmds were dosed into shake flasks with cells that express an anti-CD20 MAb. Dose
      response studies demonstrated the ability to titrate the silencing effect.
      Furthermore, siRNA addition resulted in no deleterious effects on cell growth,
      final protein titer, or specific productivity. In bioreactors, antibodies
      produced by cells following siRNA treatment exhibited improved functional
      characteristics compared to antibodies from untreated cells, including increased
      levels of afucosylation (63%), a 17-fold improvement in FCgRIIIa binding, and an
      increase in specific cell lysis by up to 30%, as determined in an Antibody
      Dependent Cellular Cytoxicity (ADCC) assay. In addition, standard purification
      procedures effectively cleared the exogenously added siRNA and transfection
      agent. Moreover, no differences were observed when other key product quality
      structural attributes were compared to untreated controls. These results
      establish that exogenous addition of siRNA represents a potentially novel
      metabolic engineering tool to improve biopharmaceutical function and quality that
      can complement existing metabolic engineering methods.

PMID- 23172737
TI  - Protein structure as a means to triage proposed PTM sites.
AB  - PTMs such as phosphorylation are often important actors in protein regulation and
      recognition. These functions require both visibility and accessibility to other
      proteins; that the modification is located at the surface of the protein.
      Currently, many repositories provide information on PTMs but structural
      information is often lacking. This study, which focuses on phosphorylation sites
      available in UniProtKB/Swiss-Prot, illustrates that most phosphorylation sites
      are indeed found at the surface of the protein, but that some sites are found
      buried in the core of the protein. Several of these identified buried
      phosphorylation sites can easily become accessible upon small conformational
      changes while others would require the whole protein to unfold and are hence most
      unlikely modification sites. Subsequent analysis of phosphorylation sites
      available in PRIDE demonstrates that taking the structure of the protein into
      account would be a good guide in the identification of the actual phosphorylated
      positions in phophoproteomics experiments. This analysis illustrates that care
      must be taken when simply accepting the position of a PTM without first analyzing
      its position within the protein structure if the latter is available.

PMID- 23172738
TI  - Evaluation of microextraction by packed sorbent and micro-liquid chromatography
      tandem mass spectrometry as a green approach in bioanalysis.
AB  - In this study the use of micro-liquid chromatography coupled to tandem mass
      spectrometry (MULC-MS/MS) was investigated in routine bioanalysis application for
      separation and quantification of pro-drug AZD6319 (developed for aldezheimer
      treatment). Microextraction by packed sorbent (MEPS) was used as sample clean-up
      method. The focus of this study was put on the evaluation of the usability of
      smaller column diameters such as 1.0 and 0.3 mm instead of 2.1 mm in bioanalysis
      application to reduce solvent consumption and sample volumes. Solvent consumption
      was reduced by 80% when a 1.0 mm column was used compared with 2.1 mm column.
      Robustness of the micro-columns in terms of accuracy and precision was
      investigated. The application of MULC-MS/MS for the quantitative analysis of
      AZD6319 in plasma samples showed good selectivity, accuracy and precision. The
      coefficients of determination (R(2) ) were >0.998 for all runs using plasma
      samples on the studied micro-columns. The inter-day accuracy values for quality
      control samples ranged from 99 to 103% and from 96 to 105% for 0.3 * 50 mm and
      1.0 * 50 mm columns, respectively. The inter-day precision values ranged from 4.0
      to 9.0% and from 4.0 to 8.0% for 0.3 * 50 and 1.0 * 50 mm columns, respectively.
      In addition the sensitivity was increased by three times using a 1.0 mm column
      compared with 2.1 mm. Furthermore, robustness of the micro-columns from different
      manufacturers was investigated.

PMID- 23172740
TI  - Engineered large spider eggcase silk protein for strong artificial fibers.

PMID- 23172739
TI  - Meiotic gene expression initiates during larval development in the sea urchin.
AB  - BACKGROUND: Meiosis is a unique mechanism in gamete production and a fundamental
      process shared by all sexually reproducing eukaryotes. Meiosis requires several
      specialized and highly conserved genes whose expression can also identify the
      germ cells undergoing gametogenic differentiation. Sea urchins are echinoderms,
      which form a phylogenetic sister group of chordates. Sea urchin embryos undergo a
      feeding, planktonic larval phase in which they construct an adult rudiment prior
      to metamorphosis. Although a series of conserved meiosis genes (e.g., dmc1, msh5,
      rad21, rad51, and sycp1) is expressed in sea urchin oocytes, we sought to
      determine when in development meiosis would first be initiated. RESULTS: We
      surveyed the expression of several meiotic genes and their corresponding proteins
      in the sea urchin Strongylocentrotus purpuratus. Surprisingly, meiotic genes are
      highly expressed not only in ovaries but beginning in larvae. Both RNA and
      protein localizations strongly suggest that meiotic gene expression initiates in
      tissues that will eventually give rise to the adult rudiment of the late larva.
      CONCLUSIONS: These results demonstrate that broad expression of the molecules
      associated with meiotic differentiation initiates prior to metamorphosis and may
      have additional functions in these cells, or mechanisms repressing their
      function, until later in development when gametogenesis begins.

PMID- 23172741
TI  - Silicon nanocrystal superlattices.

PMID- 23172742
TI  - Utility and feasibility of ultrasound-guided access in patients with critical
      limb ischemia.
AB  - BACKGROUND: Patients with advanced peripheral vascular disease (PVD) and critical
      limb ischemia (CLI) require immediate revascularization to improve blood flow and
      prevent amputation. Vascular, and especially tibial, access is arguably a very
      important part of the procedure. Utilization of ultrasound (US) guidance to
      access the peripheral vessels will maximize success and decrease the risk of
      complications. METHODS: This is a retrospective analysis of patients admitted to
      our institution between 2010 and 2011. Eighty-six patients with 191 lesions
      underwent revascularization for advanced PVD and CLI. US guidance was utilized to
      access the vascular bed in an antegrade or retrograde fashion in 100% of these
      patients. Data collected included success rate and time to access using US.
      Immediate in hospital and 30 day outcomes were also documented. RESULTS: The
      average age of patients was 69.8 years, with 69.7% male patients. All tibial
      access (33.7%) was obtained under US guidance. Obtaining vascular access using US
      was achieved in 95.3% of patients. At discharge, access site complications were
      limited to one patient (1.1%) with a pseudoaneurysm; no access complications
      related to the tibial vessels. At 30 days, there was one major amputation (1.1%)
      and one vascular access complication (1.1%). CONCLUSION: US guided access is a
      feasible and safe procedure that can aid in accessing vascular conduits in
      patients with CLI. Applying this technique across the board in CLI patients
      decreases the risk of immediate complications and facilitates accessing tibial
      arteries.

PMID- 23172743
TI  - MRI pyschophysics: an experimental framework relating image quality to diagnostic
      performance metrics.
AB  - PURPOSE: To determine the minimal image quality needed to preserve diagnostic
      performance relative to arthroscopy in the knee. MATERIALS AND METHODS: Synthetic
      noise was added to images from clinical MRI scans (three-dimensional SPACE pulse
      sequence; Siemens) from five patients who had undergone knee MRI with
      arthroscopic follow-up, resulting in 25 simulated sets of images with
      standardized signal-to-noise ratios (SNRs) of 1, 2, 5, 10, or 20. All cases were
      scored by four musculoskeletal radiologists progressing from low to high SNR and
      grading all cartilage surfaces, major ligaments and menisci on a 5-point scale.
      Receiver operator characteristic (ROC) curves were constructed for the detection
      of meniscal tears and cartilage abnormalities. The area under the ROC curve (AUC)
      was determined for each structure at each SNR level. In addition, reader
      confidence was measured and pairwise comparisons across SNR levels were
      performed. Results were compared with arthroscopy as the reference standard.
      RESULTS: ROC AUC was maximized for meniscal tears at SNR = 5 (structure specific
      CNR = 3.2) and for cartilage abnormalities at SNR = 10 (CNR = 4.2). Observer
      confidence was maximized for menisci at SNR = 5 (CNR = 8.0), for ligaments at SNR
      = 10 (CNR = 13.6) and cartilage at SNR = 10 (CNR = 8.2). CONCLUSION: For 3D
      isotropic imaging in the knee, images with SNR < 10 or CNR < 10 should be
      rejected as nondiagnostic.

PMID- 23172744
TI  - Evaluation of whole effluent toxicity data characteristics and use of Welch's T
      test in the test of significant toxicity analysis.
AB  - The U.S. Environmental Protection Agency (U.S. EPA) and state agencies evaluate
      the toxicity of effluent and surface water samples based on statistical endpoints
      derived from multiconcentration tests (e.g., no observed effect concentration,
      EC25). The test of significant toxicity (TST) analysis is a two-sample comparison
      test that uses Welch's t test to compare organism responses in a sample (effluent
      or surface water) with responses in a control or site sample. In general, any
      form of t test (Welch's t included) is appropriate only if the data meet
      assumptions of normality and homogeneous variances. Otherwise, nonparametric
      tests are recommended. TST was designed to use Welch's t as the statistical test
      for all whole effluent toxicity (WET) test data. The authors evaluated the
      suitability of using Welch's t test for analyzing two-sample toxicity (WET) data,
      and within the TST approach, by examining the distribution and variances of data
      from over 2,000 WET tests and by conducting multiple simulations of WET test
      data. Simulated data were generated having variances and nonnormal distributions
      similar to observed WET test data for control and the effluent treatment groups.
      The authors demonstrate that (1) moderately unequal variances (similar to WET
      data) have little effect on coverage of the t test or Welch t test (for normally
      distributed data), and (2) for nonnormally distributed data (similar in
      distribution to WET data) TST, using Welch's t test, has close to nominal
      coverage on the basis of simulations with up to a ninefold difference in variance
      between the effluent and control groups (~95th percentile based on observed WET
      test data).

PMID- 23172745
TI  - Progenitor cells from cartilage--no osteoarthritis-grade-specific differences in
      stem cell marker expression.
AB  - Tissue engineering efforts for the fabrication of cartilage substitutes head
      toward applicability in osteoarthritis (OA). Progenitor cells can be harvested
      from the osteoarthritic joint itself, resembling multipotent mesenchymal stromal
      cells (MSC). Our objective was to analyze MSC characteristics of those cells in
      respect to the OA-related damage of their harvest site. OA cartilage was obtained
      from six patients during alloarthroplastic knee surgery, sample grading was done
      according to Outerbridge's classification. Upon enzymatic dissociation, primary
      chondrocytes were expanded in two-dimensional monolayer culture. At distinct cell
      passages, the process of dedifferentiation was phenotypically monitored; cell
      surface expression of classical MSC markers was analyzed by flow cytometry. Cells
      were subjected to chondrogenesis and osteogenesis after their fourth passage. At
      third passage, 95% of cells became positive for cluster of differentiation
      (CD)105 and further subclassification revealed that the majority of them were
      positive for both CD73 and CD90. CD105(+) CD73(+) CD90(+) phenotype meets thus
      the minimal surface antigen criteria for MSC definition. More than one-third of
      dedifferentiated chondrocytes displayed a coexpression of CD9(+) CD166(+) CD90(+)
      and to a lesser extent CD105(+) CD73(+) CD44(+) , irrespective of the stage of
      the original cartilage degradation. Finally, we could successfully demonstrate a
      redifferentiation of these progenitors into sulfated glycosaminoglycan producing
      cells. The basic level of alkaline phosphatase activity could not be enhanced
      upon osteogenic differentiation. In conclusion, chondrogenic progenitors derived
      from OA cartilages with low or high Outerbridge's grade can be seen as a
      potential cellular source for cartilage replacement.

PMID- 23172746
TI  - Uncoupling of disease activity and structural damage. Does it matter clinically?

PMID- 23172747
TI  - Do the 2010 ACR/EULAR or ACR 1987 classification criteria predict erosive disease
      in early arthritis?
AB  - BACKGROUND: The new 2010 American College of Rheumatology (ACR)/European League
      Against Rheumatism (EULAR) classification criteria for rheumatoid arthritis (RA)
      aim at earlier diagnosis of RA compared to the 1987 ACR criteria. OBJECTIVE: To
      evaluate the ability of the 2010 ACR/EULAR and the 1987 ACR classification
      criteria to predict radiographic progression after 10 years of follow-up.
      METHODS: All early arthritis patients referred to Central Hospital in Jyvaskyla
      from 1997 to 1999 (cases with peripheral joint synovitis, other specific diseases
      excluded) were included in this 10-year follow-up study. Radiographs of hands and
      feet were analysed according to Larsen on a scale of 0-100. RESULTS: At 10 years,
      58% of the patients had an erosive disease (defined as Larsen >=2 in at least one
      joint). The discriminative power of the 2010 ACR/EULAR and the 1987 ACR criteria
      (erosive disease at 10 years) were comparable, with area under the curve 0.72
      (95% CI 0.65 to 0.79) (2010 ACR/EULAR criteria) and 0.65 (95% CI 0.58 to 0.72)
      (1987 ACR criteria). The respective sensitivities and specificities were 0.87 and
      0.70, and 0.44 and 0.47. At 10 years, median (IQR) Larsen score was 6 (0, 15)
      among patients who had fulfilled both sets of criteria, 2 (0, 8) in those who met
      the 2010 ACR/EULAR and did not meet the ACR 1987 criteria, 0 (0, 5) in those who
      met ACR 1987 criteria but did not meet 2010 ACR/EULAR criteria, and 0 (0, 2)
      among patients who did not fulfil either of the criteria. The percentage of
      patients with erosions was 69%, 64%, 32% and 26%, respectively. CONCLUSIONS: The
      ability of the 2010 ACR/EULAR and 1987 ACR classification criteria to identify
      erosive disease in early arthritis is low. The discriminative power of the 2010
      ACR/EULAR criteria of erosiveness in 10 years is slightly better than that of the
      1987 ACR criteria.

PMID- 23172748
TI  - Efficacy of biological agents in juvenile idiopathic arthritis: a systematic
      review using indirect comparisons.
AB  - OBJECTIVE: Over the past decade, the availability of biological agents for the
      treatment of juvenile idiopathic arthritis (JIA) has increased substantially.
      Because direct head-to-head trials comparing these agents are lacking, we
      indirectly compared their efficacy. METHODS: In a systematic review, all
      available efficacy data from randomised controlled trials performed in JIA with
      inclusion of biological agents were retrieved. Indirect between-drug comparisons
      (based on Bucher's method) were conducted only if trials were comparable with
      regard to design and patients' characteristics related to treatment outcome.
      RESULTS: We identified 11 randomised controlled trials. On the basis of the
      equality of the trials, six trials were grouped into two networks of evidence.
      Network 1 included withdrawal trials which evaluated etanercept, adalimumab and
      abatacept in polyarticular course JIA. Indirect comparisons identified no
      significant differences in short-term efficacy. Network 2 indirectly compared
      trials with a parallel study design investigating anakinra, tocilizumab and
      canakinumab in systemic JIA; no differences in comparative efficacy were
      identified. Although the two networks were constructed on the basis of
      comparability, small differences in trial design and case mix still existed.
      CONCLUSIONS: Because of the small number of trials and the observed differences
      between trials, no definite conclusions could be drawn about the comparative
      effectiveness of the indirectly compared biological agents. Therefore, for now,
      the paediatric rheumatologist has to rely on observational data and safety,
      practical and financial arguments. Comparability of future trials needs to be
      improved, and head-to-head trials are required to decide on the best biological
      treatment for JIA.

PMID- 23172749
TI  - Similar response rates in patients with ankylosing spondylitis and non
      radiographic axial spondyloarthritis after 1 year of treatment with etanercept:
      results from the ESTHER trial.
AB  - OBJECTIVE: We assessed whether there is a difference to etanercept (ETA)
      treatment in patients with ankylosing spondylitis (AS) compared with non
      radiographic axial SpA (nr-axSpA) patients with a disease duration <5 years.
      METHOD: AS (n=20) and nr-axSpA (n=20) patients who were treated with ETA for 1
      year were compared for differences in baseline data and treatment effect.
      Clinical, laboratory and MRI of sacroiliac joints (SI-joints) and spine were
      analysed. RESULTS: At baseline, there were no significant differences between the
      20 AS and the 20 nr-axSpA patients regarding age, disease duration, gender, HLA
      B27 and clinical disease activity in terms of Bath AS Disease Activity Index
      (BASDAI), C-reactive protein and MRI SI-joint and spine scores in the AS compared
      with the nr-axSpA group. After 1 year of treatment with ETA the treatment effect
      was similarly good in AS and nr-axSpA (reduction of BASDAI by 3.3 (95% CI 2.2 to
      3.8) vs 3.6 (95% CI 2.8 to 4.4) and reduction of AS Disease Activity Score by 1.8
      (95% CI 1.5 to 2.2) vs 1.8 (95% CI 1.5 to 2.1), respectively. CONCLUSIONS: The
      response rate to TNF-blockers does not differ between AS and nr-axSpA if the
      baseline data regarding symptom duration and disease activity are similar for the
      two groups.

PMID- 23172751
TI  - Lupuzor/P140 peptide in patients with systemic lupus erythematosus: a randomised,
      double-blind, placebo-controlled phase IIb clinical trial.
AB  - OBJECTIVES: To evaluate treatment with the peptide-based agent, Lupuzor, in a
      double-blind, randomised, placebo-controlled study of patients with systemic
      lupus erythematosus. METHODS: Patients who met >=4 of the American College of
      Rheumatology criteria, had a score of >=6 on the Systemic Lupus Erythematosus
      Disease Activity Index 2000 (SLEDAI-2K) and did not have an A score on the
      British Isles Lupus Assessment Group (BILAG)-2004 scale were eligible. 149
      intention-to-treat (ITT) patients were randomly assigned to receive Lupuzor (200
      MUg) subcutaneously every 4 weeks (n=49; group 1) or every 2 weeks (n=51; group
      2) or placebo (n=49; group 3) in addition to standard of care (SOC). A target
      population (136 ITT patients) consisting of patients having a clinical SLEDAI
      score >=6 at week 0 was considered. The clinical SLEDAI score is the SLEDAI-2K
      score obtained by omitting low complement and increased DNA binding components.
      RESULTS: In the ITT overall population, 53.1% in group 1 (p=0.048), 45.1% in
      group 2 (p=0.18) and 36.2% in the placebo group achieved an SLE Responder Index
      (SRI) response at week 12. In the target population, the results were more
      impressive: 61.9% in group 1 (p=0.016), 48.0% in group 2 (p=0.18) and 38.6% in
      the placebo group achieved an SRI response at week 12. An interim analysis
      including 114 patients from the target population demonstrated an even better
      efficacy (according to SLEDAI score) in group 1 compared with placebo (67.6% vs
      41.5% (p<0.025) at week 12 and 84.2% vs 45.8% (p<0.025) at week 24). The most
      common adverse event was a mild injection-site erythema. CONCLUSIONS: Lupuzor/200
      ug given three times at 4-week intervals during 12 weeks in addition to SOC is
      efficacious and generally well tolerated.

PMID- 23172750
TI  - Consensus statement on blocking the effects of interleukin-6 and in particular by
      interleukin-6 receptor inhibition in rheumatoid arthritis and other inflammatory
      conditions.
AB  - BACKGROUND: Since approval of tocilizumab (TCZ) for treatment of rheumatoid
      arthritis (RA) and juvenile idiopathic arthritis (JIA), interleukin 6 (IL-6)
      pathway inhibition was evaluated in trials of TCZ and other agents targeting the
      IL-6 receptor and ligand in various RA populations and other inflammatory
      diseases. This consensus document informs on interference with the IL-6 pathway
      based on evidence and expert opinion. METHODS: Preparation of this document
      involved international experts in RA treatment and RA patients. A systematic
      literature search was performed that focused on TCZ and other IL6-pathway
      inhibitors in RA and other diseases. Subsequently, incorporating available
      published evidence and expert opinion, the steering committee and a broader
      expert committee (both including RA patients) formulated the current consensus
      statement. RESULTS: The consensus statement covers use of TCZ as combination- or
      monotherapy in various RA populations and includes clinical, functional and
      structural aspects. The statement also addresses the second approved indication
      in Europe JIA and non-approved indications. Also early phase trials involving
      additional agents that target the IL-6 receptor or IL-6 were evaluated. Safety
      concerns, including haematological, hepatic and metabolic issues as well as
      infections, are addressed likewise. CONCLUSIONS: The consensus statement
      identifies points to consider when using TCZ, regarding indications,
      contraindications, screening, dose, comedication, response evaluation and safety.
      The document is aimed at supporting clinicians and informing patients,
      administrators and payers on opportunities and limitations of IL-6 pathway
      inhibition.

PMID- 23172752
TI  - Associations between statin use and changes in pain, function and structural
      progression: a longitudinal study of persons with knee osteoarthritis.
AB  - OBJECTIVES: Recently published research suggests that statins may have beneficial
      structural effects in persons with knee osteoarthritis (OA). The potential
      effects of statins on patient-reported knee pain and function have not been
      examined. We studied a large prospective community-based cohort of persons with
      knee OA to determine if statin usage was associated with changes in knee
      structure, pain and function trajectories. METHODS: Data were obtained from the
      Osteoarthritis Initiative using a subset of 2207 persons with radiographically
      suspected or confirmed knee OA. The changes in Western Ontario and McMaster
      Universities Arthritis Index (WOMAC) Pain and Physical Function scores, pain
      intensity and Kellgren-Lawrence radiographic grade over 4 years were examined.
      Data from persons were coded based on whether they were incident users of statins
      over the 4-year period. Outcome trajectories and probability of statin use were
      examined over the 4-year study period using parallel processing growth curve
      modelling. The analysis adjusted for potential confounders and determined if
      statin use predicted outcome trajectories. RESULTS: Statin users accounted for
      6.7% of the sample in year 1 and 16.4% in year 4. Statin use was not associated
      with improvements in knee pain, function or structural progression trajectories.
      The only significant finding indicated that increased duration of statin use was
      associated with worsening in WOMAC Physical Function scores over the study period
      (beta=0.161, p=0.005). CONCLUSIONS: Statin use was not associated with
      improvements in knee pain, function or structural progression over the 4-year
      study period.

PMID- 23172753
TI  - The cathelicidins LL-37 and rCRAMP are associated with pathogenic events of
      arthritis in humans and rats.
AB  - BACKGROUND: In rheumatoid arthritis (RA), neutrophil granulocytes fuel
      inflammation and damage tissue in the joint by releasing cytotoxic agents,
      antimicrobial peptides, proteases and other inflammatory mediators. The human
      cathelicidin LL-37 has recently been implicated in the development of systemic
      lupus erythematosus and psoriasis. OBJECTIVE: To elucidate if antimicrobial
      peptides (AMPs) contribute to the pathogenesis of arthritis. METHODS: Expression
      of LL-37 was determined in synovial membranes from patients with arthritis and
      control subjects. Expression of the rat cathelicidin rCRAMP and defensins was
      characterised in joints, blood and secondary lymphoid organs during pristane
      induced arthritis (PIA) in rats and in a transfer model of PIA induced by CD4 T
      cells. Serum samples of rats with arthritis were tested for IgG and IgM
      autoantibodies against rCRAMP by immunoblot and for interferon (IFNalpha) by
      ELISA. RESULTS: Cathelicidins are strongly upregulated in RA synovial membranes
      and in joints from rats with arthritis as compared with healthy joints.
      Expression was most prominent in neutrophil granulocytes and
      macrophages/osteoclasts. Cathelicidin expression is also upregulated in the blood
      and spleen of pristane-injected rats, with strongest expression detected in
      activated CD62L- cells coexpressing granulocyte and monocyte markers. Pristane
      injection caused accumulation of low-density granulocytes in the blood. After
      pristane injection, the increased expression of rCRAMP coincided with higher
      levels of cell death, raised levels of interferon (IFN)alpha and development of
      autoantibodies. CONCLUSIONS: Our results show strong upregulation of
      cathelicidins and beta-defensins coinciding with pathological events of
      arthritis. Higher expression and release of AMPs might contribute to development
      and/or maintenance of disease by systemic or local mechanisms.

PMID- 23172755
TI  - Estimating a time-dependent concordance index for survival prediction models with
      covariate dependent censoring.
AB  - Given a predictive marker and a time-to-event response variable, the proportion
      of concordant pairs in a data set is called concordance index. A specifically
      useful marker is the risk predicted by a survival regression model. This article
      extends the existing methodology for applications where the length of the follow
      up period depends on the predictor variables. A class of inverse probability of
      censoring weighted estimators is discussed in which the estimates rely on a
      working model for the conditional censoring distribution. The estimators are
      consistent for a truncated concordance index if the working model is correctly
      specified and if the probability of being uncensored at the truncation time is
      positive. In this framework, all kinds of prediction models can be assessed, and
      time trends in the discrimination ability of a model can be captured by varying
      the truncation time point. For illustration, we re-analyze a study on risk
      prediction for prostate cancer patients. The effects of misspecification of the
      censoring model are studied in simulated data.

PMID- 23172756
TI  - Plant proteins under oxidative attack.
AB  - Reactive oxygen and nitrogen species can modify various biomolecules, including
      proteins. The resulting protein modifications are highly diverse, can be
      reversible as well as irreversible, and might affect protein structure and
      function. Besides random modifications, targeted modifications at specific amino
      acids in surface-accessible protein regions occur. These changes are of
      particular interest as, e.g. by altering the local protein conformation; they
      might initiate specific (oxidative) signaling pathways. Here, we focus on two
      protein modifications that are found under conditions of oxidative stress in
      plants: oxidation of the sulfur-containing methionine and nitration of tyrosine.
      We review the functional consequences caused by the oxidation of several plant
      proteins and line-up those proteomics technologies that are amenable to study
      these selected modifications.

PMID- 23172754
TI  - Implication of IL-2/IL-21 region in systemic sclerosis genetic susceptibility.
AB  - OBJECTIVE: The interleukin 2 (IL-2) and interleukin 21 (IL-21) locus at
      chromosome 4q27 has been associated with several autoimmune diseases, and both
      genes are related to immune system functions. The aim of this study was to
      evaluate the role of the IL-2/IL-21 locus in systemic sclerosis (SSc). PATIENTS
      AND METHODS: The case control study included 4493 SSc Caucasian patients and 5856
      healthy controls from eight Caucasian populations (Spain, Germany, The
      Netherlands, USA, Italy, Sweden, UK and Norway). Four single nucleotide
      polymorphisms (rs2069762, rs6822844, rs6835457 and rs907715) were genotyped using
      TaqMan allelic discrimination assays. RESULTS: We observed evidence of
      association of the rs6822844 and rs907715 variants with global SSc (pc=6.6E-4 and
      pc=7.2E-3, respectively). Similar statistically significant associations were
      observed for the limited cutaneous form of the disease. The conditional
      regression analysis suggested that the most likely genetic variation responsible
      for the association was the rs6822844 polymorphism. Consistently, the rs2069762A
      rs6822844T-rs6835457G-rs907715T allelic combination showed evidence of
      association with SSc and limited cutaneous SSc subtype (pc=1.7E-03 and pc=8E-4,
      respectively). CONCLUSIONS: These results suggested that the IL-2/IL-21 locus
      influences the genetic susceptibility to SSc. Moreover, this study provided
      further support for the IL-2/IL-21 locus as a common genetic factor in autoimmune
      diseases.

PMID- 23172757
TI  - Early development of the thymus in Xenopus laevis.
AB  - BACKGROUND: Although Xenopus laevis has been a model of choice for comparative
      and developmental studies of the immune system, little is known about
      organogenesis of the thymus, a primary lymphoid organ in vertebrates. Here we
      examined the expression of three transcription factors that have been
      functionally associated with pharyngeal gland development, gcm2, hoxa3, and
      foxn1, and evaluated the neural crest contribution to thymus development.
      RESULTS: In most species Hoxa3 is expressed in the third pharyngeal pouch
      endoderm where it directs thymus formation. In Xenopus, the thymus primordium is
      derived from the second pharyngeal pouch endoderm, which is hoxa3-negative,
      suggesting that a different mechanism regulates thymus formation in frogs. Unlike
      other species foxn1 is not detected in the epithelium of the pharyngeal pouch in
      Xenopus, rather, its expression is initiated as thymic epithelial cell starts to
      differentiate and express MHC class II molecules. Using transplantation
      experiments we show that while neural crest cells populate the thymus primordia,
      they are not required for the specification and initial development of this organ
      or for T-cell differentiation in frogs. CONCLUSIONS: These studies provide novel
      information on early thymus development in Xenopus, and highlight a number of
      features that distinguish Xenopus from other organisms.

PMID- 23172759
TI  - Transradial percutaneous coronary intervention for chronic total occlusion using
      sheathless technique and retrograde approach.
AB  - The use of 5 or 6 Fr sheath in transradial (TR) approach is often required due to
      the relative small radial artery size. A sheathless approach may overcome the
      limitation of small radial size which limits the TR approach. Our case showed
      successful angioplasty of the right coronary artery chronic total occlusion (CTO)
      by bilateral TR approaches, utilizing a 7-Fr guide (7 Fr BL 3.5, 85 cm) for a
      retrograde sheathless approach, and a 6-Fr Ikari 3.5 guide catheter for an
      antegrade approach. The sheathless TR technique can minimize vascular trauma and
      increase back-up support for successful coronary intervention in CTO.

PMID- 23172758
TI  - Pasireotide is more effective than octreotide in reducing hepatorenal
      cystogenesis in rodents with polycystic kidney and liver diseases.
AB  - In polycystic liver (PLD) and kidney (PKD) diseases, increased cyclic adenosine
      monophosphate (cAMP) levels trigger hepatorenal cystogenesis. A reduction of the
      elevated cAMP by targeting somatostatin receptors (SSTRs) with octreotide (OCT; a
      somatostatin analog that preferentially binds to SSTR2) inhibits cyst growth.
      Here we compare the effects of OCT to pasireotide (PAS; a more potent
      somatostatin analog with broader receptor specificity) on: (1) cAMP levels, cell
      cycle, proliferation, and cyst expansion in vitro using cholangiocytes derived
      from control and PCK rats (a model of autosomal recessive PKD [ARPKD]), healthy
      human beings, and patients with autosomal dominant PKD (ADPKD); and (2)
      hepatorenal cystogenesis in vivo in PCK rats and Pkd2(WS25/-) mice (a model of
      ADPKD). Expression of SSTRs was assessed in control and cystic cholangiocytes of
      rodents and human beings. Concentrations of insulin-like growth factor 1 (IGF1)
      and vascular endothelial growth factor (VEGF) (both involved in indirect action
      of somatostatin analogs), and expression and localization of SSTRs after
      treatment were evaluated. We found that PAS was more potent (by 30%-45%) than OCT
      in reducing cAMP and cell proliferation, affecting cell cycle distribution,
      decreasing growth of cultured cysts in vitro, and inhibiting hepatorenal
      cystogenesis in vivo in PCK rats and Pkd2(WS25/-) mice. The levels of IGF1 (but
      not VEGF) were reduced only in response to PAS. Expression of SSTR1 and SSTR2
      (but not SSTR3 and SSTR5) was decreased in cystic cholangiocytes compared to
      control. Although both OCT and PAS increased the immunoreactivity of SSTR2, only
      PAS up-regulated SSTR1; neither drug affected cellular localization of SSTRs.
      CONCLUSION: PAS is more effective than OCT in reducing hepatorenal cystogenesis
      in rodent models; therefore, it might be more beneficial for the treatment of PKD
      and PLD.

PMID- 23172760
TI  - Discrimination of metastatic lymph nodes in patients with gastric carcinoma using
      diffusion-weighted imaging.
AB  - PURPOSE: To determine the accuracy of diffusion-weighted imaging (DWI) in
      discrimination of metastatic lymph nodes (LNs) in gastric carcinoma with rigorous
      histopathological correlation. MATERIALS AND METHODS: With Institutional Review
      Board (IRB) approval, 28 patients with gastric carcinoma underwent magnetic
      resonance imaging (MRI) and DWI before surgery. LNs were resected at surgery and
      thereafter submitted for histopathological analyses. All histopathologically
      identified LNs (>= 5 mm) that exactly matched the location and size of nodes on
      MRI/DWI were submitted to lesion-by-lesion analyses. Short-axis diameter, border
      irregularity, enhanced patterns, and apparent diffusion coefficient (ADC) values
      of each LN were recorded. Each measurement was compared between metastatic and
      benign LNs, confirmed by nodal histopathology. A receiver operating
      characteristic (ROC) curve was generated to evaluate the capability of
      morphological and ADC measurements in distinguishing metastatic lymph nodes.
      RESULTS: The median ADC value of metastatic nodes was significantly lower (1.28 *
      10(-3) mm(2) /sec; interquartile range, 1.20-1.31) than that of benign (1.55;
      1.47-1.73) nodes (P < 0.001). DWI showed greater diagnostic accuracy in
      determining metastatic nodes (AUC = 0.857) than the combined morphological
      measurements of short-axis, border irregularity, and enhanced patterns (AUC =
      0.746, P = 0.03). Adding ADC values to the combined morphologic criteria
      demonstrated the greatest predictive power (AUC = 0.889). CONCLUSION: DWI may
      provide great potential in effective discrimination of metastatic LNs in gastric
      carcinoma.

PMID- 23172761
TI  - The Informant Questionnaire on Cognitive Decline in the Elderly individuals in
      screening mild cognitive impairment with or without functional impairment.
AB  - The Informant Questionnaire on Cognitive Decline in the Elderly individuals
      (IQCODE) is a reliable, validated informant-based instrument. Most of the studies
      well support the validity of the IQCODE in dementia screening, but the
      sensitivity of the rating scale at the early stage during the course of dementia
      is limited. In this study, we investigate the utility of the IQCODE for patients
      with mild cognitive impairment (MCI) and the discriminative power of the IQCODE
      in patients having MCI with and without functional impairment. The samples
      included mild Alzheimer disease (AD, N=280), MCI ([N=657], further divided into 2
      subgroups: patients with MCI having functional impairment [MCI-fi, N=357] and
      patients having MCI without functional impairment [MCI-fn, N=300]), and normal
      cognition (NC, N=274). The IQCODE, Mini-Mental State Examination (MMSE), and
      other neuropsychological tests were administered to all participants. Logistic
      regression and receiver-operating characteristic (ROC) curves were used to
      evaluate the diagnostic ability of the IQCODE, compared to the MMSE. The optimal
      cutoff scores of the IQCODE were 3.19 for the MCI (sensitivity/specificity:
      0.979/0.714) and MCI-fn (0.900/0.817), 3.25 for the MCI-fi (0.978/0.701), and
      3.31 for mild AD (0.893/0.779), while the MMSE was identical, that is 26, for
      both MCI and its functional normal and functional impaired subgroups
      (0.892/0.755, 0.867/0.745, and 0.913/0.745, respectively) and 24 for mild AD
      (0.807/0.836). The discriminating accuracy of the IQCODE was slightly superior to
      that of the MMSE but did not reach statistical significance. Our study suggests
      that the IQCODE might be useful in screening for MCI, with hierarchical scores
      indicating functional normal or impaired.

PMID- 23172762
TI  - The frontal assessment battery in the differential diagnosis of dementia.
AB  - AIM: The Frontal Assessment Battery (FAB) has been used in different clinical
      settings as a valuable quick bedside test for executive dysfunction. The aim of
      the study was to evaluate clinical utility of the FAB for differential diagnosis
      of Alzheimer disease (AD), subcortical vascular cognitive impairment (scVCI), and
      frontotemporal lobar degeneration (FTLD). METHODS: Scores of the total FAB test
      and subtests were compared between consecutive series of 37 patients with AD, 31
      patients with scVCI, 13 patients with FTLD, and 29 cognitively healthy
      individuals. RESULTS: There was no statistically significant difference in the
      total FAB scores among the groups of patients with dementia. When comparing
      subtest scores, patients with FTLD had significantly lower scores on the lexical
      fluency subtest compared to the patients with AD (P<.001) or scVCI (P<.001);
      patients with scVCI had significantly lower scores on the motor series subtest
      compared to patients with FTLD (P=.02) and AD (P=.035) and on conflicting
      instructions subtest compared to patients with AD (P=.033). CONCLUSION: Some FAB
      subtests might enhance diagnostic accuracy taking into account clinical history
      and other tests of executive function.

PMID- 23172763
TI  - Predicting functional impairments in cognitively impaired older adults using the
      Minnesota Cognitive Acuity Screen.
AB  - Despite their growing use, few studies have examined the associations between
      patients' performance on brief telephone-based cognitive assessments and their
      functional status. The purpose of this study was to examine the relationship
      between the Minnesota Cognitive Acuity Screen (MCAS), a very brief telephone
      based dementia screening instrument, and functional impairment as rated by the
      Clinical Dementia Rating (CDR) scale in a sample of 176 individuals diagnosed
      with mild cognitive impairment or dementia. Results showed lower MCAS scores were
      correlated with poorer daily function as measured by CDR global scores and domain
      scores, and the MCAS orientation subscale was one of the strongest subscales in
      predicting functional status as it was uniquely predictive of all CDR domains.
      Findings suggest the MCAS appears to be useful in predicting patients' level of
      daily function and may be useful for quickly and easily monitoring patients'
      cognitive and functional status over time.

PMID- 23172765
TI  - Cognitive impairment in Parkinson disease: impact on quality of life, disability,
      and caregiver burden.
AB  - AIM: To compare quality of life, level of disability, and caregiver burden in 3
      groups of people with Parkinson disease (PD): those with mild cognitive
      impairment (PD-MCI), those with dementia (PDD), and those with no cognitive
      impairment (PD-NC). BACKGROUND: Although the cognitive profile of those with PD
      MCI and PDD has been well described, little is known about the personal and
      clinical impact of cognitive impairment and its impact on caregivers. METHOD:
      Quality of life and disability were measured in 3 groups of participants with PD
      (PD-NC, n=54; PD-MCI, n=48; and PDD, n=25). The PD-MCI group was classified using
      Movement Disorder Society Task Force consensus criteria. Caregivers (n=102) in
      the 3 groups were assessed using the Zarit Burden Inventory. RESULTS: Both
      quality of life and caregiver burden were similar in the 2 groups without
      dementia but were significantly different in those with PDD. In contrast, global
      disability was progressively greater as cognition declined across the 3 PD
      groups: PD-NC<PD-MCI<PDD and on the Activities of Daily Living scale a step up in
      impairment was seen with the presence of any cognitive impairment. CONCLUSIONS:
      The presence of dementia significantly increases caregiver burden and decreases
      quality of life. However, even mild levels of cognitive impairment increase
      disability and overall functional impairment progresses in tandem with cognitive
      decline.

PMID- 23172764
TI  - Caregiver burden in Parkinson disease with dementia compared to Alzheimer disease
      in Korea.
AB  - We compared caregiver burden in Parkinson disease with dementia (PDD) to that in
      Alzheimer disease (AD) and examined the factors contributing to the burden in
      PDD. Totally, 42 patients with PDD and 109 patients with AD and their caregivers
      participated in this study. The caregiver burden was measured using the Burden
      Interview (BI). Scores of Barthel activities of daily living (BADLs), Mini-Mental
      State Examination, Clinical Dementia Rating of patients, and score of Center for
      Epidemiologic Studies Depression scale, and Euro-quality of life of the
      caregivers were examined. The Unified Parkinson's Disease Rating Scale (UPDRS)
      and Hoehn and Yahr stage of the patients were administered to assess burden
      relating to parkinsonism on PDD. We used multiple linear regression to assess the
      predictors. The BI of caregivers was higher in PDD (47.9, Standard deviation
      [SD]: 3.8) than in AD (36.3, SD:2.1). In the AD group, the BI was predicted by
      cognitive function ((beta+/-SE: -0.8+/-0.4, P value=04) and basic ADL status of
      patients (beta+/-SE: -1.3+/-0.1, P<.001), depressive symptoms (beta+/-SE: 1.1+/
      0.1, P<.001), and poor quality of life (beta+/-SE: -0.2+/-0.1, P=.017) in
      caregivers. In PDD group, BI was predicted only by scores of Part 1 on the UPDRS
      (beta+/-SE: 2.9+/-1.3, P=.03) of patients and depressive symptoms (beta+/-SE:
      1.1+/-0.2, P<.001) of the caregivers. We concluded the caregiver burden is higher
      in PDD than in AD and factors predicting burden are different in AD and PDD. In
      patients with PDD, the neuropsychiatric problems are the major contributor to
      caregiver burden.

PMID- 23172766
TI  - Outcome of infants with prenatally diagnosed congenital heart disease delivered
      outside specialist paediatric cardiac centres.
AB  - OBJECTIVE: To determine the outcome of neonates with a suspected antenatal
      diagnosis of congenital heart disease (CHD) who were delivered away from a
      paediatric cardiothoracic centre and were initially managed in a level 3 Neonatal
      Intensive Care Unit. METHODS: An 18-year ongoing study conducted in a single
      institution. RESULTS: Between 1992 and 2009, 143 fetuses with suspected CHD were
      identified, and 124 babies were delivered locally. 13 babies with a normal
      postnatal echocardiogram and six with isolated arrhythmias were excluded from the
      study. Structural CHD was confirmed in 105 infants; of these, 94 (90%) survived
      the neonatal period. Of the 11 neonatal deaths, only four of these infants
      underwent surgery; most had additional risk factors including: prematurity, very
      low birth weight, and genetic and other structural congenital anomalies.
      CONCLUSIONS: This study demonstrates that appropriately selected infants with
      antenatally diagnosed CHD can be safely delivered and initially managed in a non
      cardiac centre during their neonatal period. Deliveries need to be carefully
      planned with close collaboration among neonatologists, obstetricians, paediatric
      cardiologists, mid-wives and parents.

PMID- 23172768
TI  - Callous-unemotional traits and response to functional family therapy in
      adolescent offenders.
AB  - OBJECTIVE: The current study examined whether callous-unemotional (CU) traits
      moderated the effectiveness of Functional Family Therapy for juvenile justice
      involved adolescents. METHOD: Participants were all youths (n = 134) who had been
      arrested and participated in an FFT program provided in a community mental health
      center over a 20-month period (mean age 15.34, 71.6% males, 59% African
      American). Parent and self-report ratings of emotional, behavioral, and social
      functioning, multi-informant ratings of treatment progress, and probation/arrest
      records were used as outcome indicators. RESULTS: CU traits were associated with
      poorer behavioral, emotional, and social adjustment prior to treatment but they
      were also associated with greater improvements in adjustment over the course of
      treatment. CU traits were not associated with significantly lower rates of
      participation or higher rates of treatment dropout, and the association between
      CU traits and risk for violent charges decreased after treatment at 6- and 12
      month follow-ups. However, CU traits were still correlated with poorer levels of
      adjustment post-treatment, less perceived change over treatment by youth and
      their parents, and increased likelihood of violent offending during treatment.
      CONCLUSIONS: The results of this study indicate that FFT can lead to improvements
      in youth with CU traits; however, they enter treatment with a greater number of
      symptoms and are at higher risk for committing violence during treatment than
      other youth.

PMID- 23172767
TI  - Antemortem cranial MRI compared with postmortem histopathologic examination of
      the brain in term infants with neonatal encephalopathy following perinatal
      asphyxia.
AB  - AIM: To compare antemortem cranial MRI with postmortem histopathological
      examination of the brain in full-term infants with neonatal encephalopathy
      following perinatal asphyxia. PATIENTS AND METHODS: In this retrospective
      observational cohort study, 23 infants with neonatal encephalopathy who
      subsequently died, were analysed. Infants underwent antemortem cranial MRI and
      postmortem histopathological examination of the brain. MRI included T1, T2 and
      diffusion-weighted sequences. Histopathology included staining with H&E, and
      monoclonal antibodies to CD68 and HLA-DR. Histological abnormalities were
      compared with MRI in 10 different brain regions. RESULTS: All neonates underwent
      cranial MRI within 7 days after birth (median day 3, IQR 2-4 days). Infants died
      on median day 4 (IQR 2-5 days). Histopathology demonstrated significantly
      (p=0.0016) more abnormal regions (median 10, IQR 7-10) per patient than did MRI
      (median 8, IQR 5-9). The number of cases with abnormalities in the thalamus,
      basal ganglia, posterior limb of the internal capsule (PLIC), cerebral cortex and
      cerebellum were not significantly different between MRI and histopathology. By
      contrast, the hippocampus (70% vs 96%, p=0.047), cerebral white matter (anterior
      65% vs 96%, p=0.022, posterior 61% vs 91%, p=0.035) and brainstem (57% vs 96%,
      p=0.004) were confirmed to be affected more often on histopathological
      examination than with MRI. CONCLUSIONS: Whereas early postnatal MR imaging is
      excellent in detecting injury to the basal ganglia and thalamus, PLIC, cortex and
      cerebellum, it may underestimate injury to the hippocampus, cerebral white
      matter, and the brainstem in term infants with neonatal encephalopathy following
      perinatal asphyxia.

PMID- 23172769
TI  - Enzymatic processes for the purification of trehalose.
AB  - A dual-enzyme process aiming at facilitating the purification of trehalose from
      maltose is reported in this study. Enzymatic conversion of maltose to trehalose
      usually leads to the presence of significant amount of glucose, by-product of the
      reaction, and unreacted maltose. To facilitate the separation of trehalose from
      glucose and unreacted maltose, sequential conversion of maltose to glucose and
      glucose to gluconic acid under the catalysis of glucoamylase and glucose oxidase,
      respectively, is studied. This study focuses on the hydrolysis of maltose with
      immobilized glucoamylase on Eupergit(r) C and CM Sepharose. CM Sepharose
      exhibited a higher protein adsorption capacity, 49.35 +/- 1.43 mg/g, and was thus
      selected as carrier for the immobilization of glucoamylase. The optimal reaction
      temperature and reaction pH of the immobilized glucoamylase for maltose
      hydrolysis were identified as 40 degrees C and 4.0, respectively. Under such
      conditions, the unreacted maltose in the product stream of trehalose synthase
      catalyzed reaction was completely converted to glucose within 35 min, without
      detectable trehalose degradation. The conversion of maltose to glucose could be
      maintained at 0.92 even after 80 cycles in repeated-batch operations. It was also
      demonstrated that glucose thus generated could be readily oxidized into gluconic
      acid, which can be easily separated from trehalose. We thus believe the proposed
      process of maltose hydrolysis with immobilized glucoamylase, in conjunction with
      trehalose synthase-catalyzed isomerization and glucose oxidase-catalyzed
      oxidation, is promising for the production and purification of trehalose on
      industrial scales.

PMID- 23172770
TI  - Ties between event times and jump times in the Cox model.
AB  - Methods for dealing with tied event times in the Cox proportional hazards model
      are well developed. Also, the partial likelihood provides a natural way to handle
      covariates that change over time. However, ties between event times and the times
      that discrete time-varying covariates change have not been systematically studied
      in the literature. In this article, we discuss the default behavior of current
      software and propose some simple methods for dealing with such ties. A simulation
      study shows that the default behavior of current software can lead to biased
      estimates of the coefficient of a binary time-varying covariate and that two
      proposed methods (Random Jitter and Equally Weighted) reduce estimation bias. The
      proposed methods can be easily implemented with existing software. The methods
      are illustrated on the well-known Stanford heart transplant data and data from a
      study on intimate partner violence and smoking.

PMID- 23172771
TI  - Neural responses to expression and gaze in the posterior superior temporal sulcus
      interact with facial identity.
AB  - Neural models of human face perception propose parallel pathways. One pathway
      (including posterior superior temporal sulcus, pSTS) is responsible for
      processing changeable aspects of faces such as gaze and expression, and the other
      pathway (including the fusiform face area, FFA) is responsible for relatively
      invariant aspects such as identity. However, to be socially meaningful, changes
      in expression and gaze must be tracked across an individual face. Our aim was to
      investigate how this is achieved. Using functional magnetic resonance imaging, we
      found a region in pSTS that responded more to sequences of faces varying in gaze
      and expression in which the identity was constant compared with sequences in
      which the identity varied. To determine whether this preferential response to
      same identity faces was due to the processing of identity in the pSTS or was a
      result of interactions between pSTS and other regions thought to code face
      identity, we measured the functional connectivity between face-selective regions.
      We found increased functional connectivity between the pSTS and FFA when
      participants viewed same identity faces compared with different identity faces.
      Together, these results suggest that distinct neural pathways involved in
      expression and identity interact to process the changeable features of the face
      in a socially meaningful way. 

PMID- 23172773
TI  - Common mechanisms of spatial attention in memory and perception: a tactile dual
      task study.
AB  - Orienting attention to locations in mnemonic representations engages processes
      that functionally and anatomically overlap the neural circuitry guiding
      prospective shifts of spatial attention. The attention-based rehearsal account
      predicts that the requirement to withdraw attention from a memorized location
      impairs memory accuracy. In a dual-task study, we simultaneously presented retro
      cues and pre-cues to guide spatial attention in short-term memory (STM) and
      perception, respectively. The spatial direction of each cue was independent of
      the other. The locations indicated by the combined cues could be compatible (same
      hand) or incompatible (opposite hands). Incompatible directional cues decreased
      lateralized activity in brain potentials evoked by visual cues, indicating
      interference in the generation of prospective attention shifts. The detection of
      external stimuli at the prospectively cued location was impaired when the
      memorized location was part of the perceptually ignored hand. The disruption of
      attention-based rehearsal by means of incompatible pre-cues reduced memory
      accuracy and affected encoding of tactile test stimuli at the retrospectively
      cued hand. These findings highlight the functional significance of spatial
      attention for spatial STM. The bidirectional interactions between both tasks
      demonstrate that spatial attention is a shared neural resource of a capacity
      limited system that regulates information processing in internal and external
      stimulus representations. 

PMID- 23172772
TI  - Reading front to back: MEG evidence for early feedback effects during word
      recognition.
AB  - Magnetoencephalography studies in humans have shown word-selective activity in
      the left inferior frontal gyrus (IFG) approximately 130 ms after word
      presentation ( Pammer et al. 2004; Cornelissen et al. 2009; Wheat et al. 2010).
      The role of this early frontal response is currently not known. We tested the
      hypothesis that the IFG provides top-down constraints on word recognition using
      dynamic causal modeling of magnetoencephalography data collected, while subjects
      viewed written words and false font stimuli. Subject-specific dipoles in left and
      right occipital, ventral occipitotemporal and frontal cortices were identified
      using Variational Bayesian Equivalent Current Dipole source reconstruction. A
      connectivity analysis tested how words and false font stimuli differentially
      modulated activity between these regions within the first 300 ms after stimulus
      presentation. We found that left inferior frontal activity showed stronger
      sensitivity to words than false font and a stronger feedback connection onto the
      left ventral occipitotemporal cortex (vOT) in the first 200 ms. Subsequently, the
      effect of words relative to false font was observed on feedforward connections
      from left occipital to ventral occipitotemporal and frontal regions. These
      findings demonstrate that left inferior frontal activity modulates vOT in the
      early stages of word processing and provides a mechanistic account of top-down
      effects during word recognition. 

PMID- 23172775
TI  - The neural signature of the own-race bias: evidence from event-related
      potentials.
AB  - Participants are more accurate at remembering faces of their own relative to
      another ethnic group (own-race bias, ORB). This phenomenon has been explained by
      reduced perceptual expertise, or alternatively, by the categorization of other
      race faces into social out-groups and reduced effort to individuate such faces.
      We examined event-related potential (ERP) correlates of the ORB, testing
      recognition memory for Asian and Caucasian faces in Caucasian and Asian
      participants. Both groups demonstrated a significant ORB in recognition memory.
      ERPs revealed more negative N170 amplitudes for other-race faces in both groups,
      probably reflecting more effortful structural encoding. Importantly, the
      ethnicity effect in left-hemispheric N170 during learning correlated
      significantly with the behavioral ORB. Similarly, in the subsequent N250, both
      groups demonstrated more negative amplitudes for other-race faces, and during
      test phases, this effect correlated significantly with the ORB. We suggest that
      ethnicity effects in the N170 reflect an early categorization of other-race faces
      into a social out-group, resulting in less efficient encoding and thus decreased
      memory. Moreover, ethnicity effects in the N250 may represent the "tagging" of
      other-race faces as perceptually salient, which hampers the recognition of these
      faces. 

PMID- 23172774
TI  - Encoding of rules by neurons in the human dorsolateral prefrontal cortex.
AB  - We use rules to extend learned behavior beyond specific instances to general
      scenarios. The prefrontal cortex (PFC) is thought to play an important role in
      representing rules, as evidenced by subjects who have difficulty in following
      rules after PFC damage and by animal studies demonstrating rule sensitivity of
      individual PFC neurons. How rules are instantiated at the single-neuronal level
      in the human brain, however, remains unclear. Here, we recorded from individual
      neurons in the human dorsolateral prefrontal cortex (DLPFC) as subjects performed
      a task in which they evaluated pairs of images using either of 2 abstract rules.
      We find that DLPFC neurons selectively encoded these rules while carrying little
      information about the subjects' responses or the sensory cues used to guide their
      decisions. 

PMID- 23172776
TI  - Drastic effect of germline TP53 missense mutations in Li-Fraumeni patients.
AB  - In contrast to other tumor suppressor genes, the majority of TP53 alterations are
      missense mutations. We have previously reported that in the Li-Fraumeni syndrome
      (LFS), germline TP53 missense mutations are associated with an earlier age of
      tumor onset. In a larger series, we observed that mean age of tumor onset in
      patients harboring dominant negative missense mutations and clearly null
      mutations was 22.6 and 37.5 years, respectively. To assess the impact of
      heterozygous germline TP53 mutations in the genetic context of the patients, we
      developed a new functional assay of the p53 pathway on the basis of induction of
      DNA damage in Epstein-Barr-virus-immortalized lymphocytes, followed by
      comparative gene-expression profiling. In wild-type lymphocytes, we identified a
      core of 173 genes whose expression was induced more than twofold, of which 46
      were known p53 target genes. In LFS lymphocytes with canonical missense
      mutations, the number of induced genes and the level of known p53 target genes
      induction were strongly reduced as compared with controls and LFS lymphocytes
      with null mutations. These results show that certain germline missense TP53
      mutations, such as those with dominant negative effect, dramatically alter the
      response to DNA damage. This probably explains why TP53 alterations are
      predominantly missense mutations.

PMID- 23172777
TI  - 3D-QSAR-assisted drug design: identification of a potent quinazoline-based Aurora
      kinase inhibitor.
AB  - We describe the 3D-QSAR-assisted design of an Aurora kinase A inhibitor with
      improved physicochemical properties, in vitro activity, and in vivo
      pharmacokinetic profiles over those of the initial lead. Three different 3D-QSAR
      models were built and validated by using a set of 66 pyrazole (Model I) and
      furanopyrimidine (Model II) compounds with IC(50)  values toward Aurora kinase A
      ranging from 33 nM to 10.5 MUM. The best 3D-QSAR model, Model III, constructed
      with 24 training set compounds from both series, showed robustness (r(2) (CV)
      =0.54 and 0.52 for CoMFA and CoMSIA, respectively) and superior predictive
      capacity for 42 test set compounds (R(2) (pred) =0.52 and 0.67, CoMFA and
      CoMSIA). Superimposition of CoMFA and CoMSIA Model III over the crystal structure
      of Aurora kinase A suggests the potential to improve the activity of the ligands
      by decreasing the steric clash with Val147 and Leu139 and by increasing
      hydrophobic contact with Leu139 and Gly216 residues in the solvent-exposed region
      of the enzyme. Based on these suggestions, the rational redesign of
      furanopyrimidine 24 (clog P=7.41; Aurora A IC(50) =43 nM; HCT-116 IC(50) =400 nM)
      led to the identification of quinazoline 67 (clog P=5.28; Aurora A IC(50) =25 nM;
      HCT-116 IC(50) =23 nM). Rat in vivo pharmacokinetic studies showed that 67 has
      better systemic exposure after i.v. administration than 24, and holds potential
      for further development.

PMID- 23172778
TI  - Manganese-doped highly ordered mesoporous silicate with high efficiency for
      oxidation suppression.
AB  - Herein, we demonstrate a facile approach to manganese-doped highly ordered
      mesoporous silicate with oxidation-suppression function. As biocompatible
      supports of guest ions, the ordered mesoporous silicate was synthesized by
      evaporation-induced self-assembly. The phase-transition from disordered to
      lamellar structures in the highly ordered mesoporous structure of these porosity
      tuned materials was controlled by adjusting the concentration of a lab-made
      polystyrene-b-polyethylene oxide copolymer. Manganese was successfully
      incorporated as a guest in the hexagonally packed mesoporous silicate by using an
      ultrasound-assisted technique. The incorporation of manganese ions into the pores
      of a mesoporous silicate support could be induced for host-guest functional
      applications. Manganese-doped mesoporous silicate structures have been examined
      for their use as antioxidizing agents by electron spin resonance (ESR)
      measurements and radical-scavenging tests. The manganese atoms in the mesoporous
      structures could act in a free-radical-scavenging capacity, much like manganese
      nanoparticles. The high efficiency of their oxidation-suppression function is
      extended for application to catalytic products.

PMID- 23172779
TI  - 'Rheumatology for the advanced age': a report of the West Midlands rheumatology
      forum autumn meeting 2012.

PMID- 23172780
TI  - Global epidemiology of hepatitis C virus infection: new estimates of age-specific
      antibody to HCV seroprevalence.
AB  - In efforts to inform public health decision makers, the Global Burden of
      Diseases, Injuries, and Risk Factors 2010 (GBD2010) Study aims to estimate the
      burden of disease using available parameters. This study was conducted to collect
      and analyze available prevalence data to be used for estimating the hepatitis C
      virus (HCV) burden of disease. In this systematic review, antibody to HCV (anti
      HCV) seroprevalence data from 232 articles were pooled to estimate age-specific
      seroprevalence curves in 1990 and 2005, and to produce age-standardized
      prevalence estimates for each of 21 GBD regions using a model-based meta
      analysis. This review finds that globally the prevalence and number of people
      with anti-HCV has increased from 2.3% (95% uncertainty interval [UI]: 2.1%-2.5%)
      to 2.8% (95% UI: 2.6%-3.1%) and >122 million to >185 million between 1990 and
      2005. Central and East Asia and North Africa/Middle East are estimated to have
      high prevalence (>3.5%); South and Southeast Asia, sub-Saharan Africa, Andean,
      Central, and Southern Latin America, Caribbean, Oceania, Australasia, and
      Central, Eastern, and Western Europe have moderate prevalence (1.5%-3.5%);
      whereas Asia Pacific, Tropical Latin America, and North America have low
      prevalence (<1.5%). CONCLUSION: The high prevalence of global HCV infection
      necessitates renewed efforts in primary prevention, including vaccine
      development, as well as new approaches to secondary and tertiary prevention to
      reduce the burden of chronic liver disease and to improve survival for those who
      already have evidence of liver disease.

PMID- 23172781
TI  - Air pressure-induced susceptibility changes in vascular reactivity studies using
      BOLD MRI.
AB  - PURPOSE: To investigate whether compressed air during air-cuff inflation in
      vascular reactivity studies could induce aberrant blood oxygenation level
      dependent (BOLD) signal change. MATERIALS AND METHODS: Magnetic resonance imaging
      (MRI) experiments were performed on a whole-body 3 T scanner. The pattern of T2*
      signal change measured from a phantom simulating the lower limb was assessed
      while a thigh cuff was inflated and deflated. MR spectroscopy was performed on a
      head phantom wrapped using a hand-cuff to determine the relationship between
      water peak linewidth and applied cuff pressure. Calf muscles from 14 normal
      subjects were examined to identify aberrant T2* signal changes in the occluded
      and nonoccluded legs. RESULTS: A sudden T2* signal drop was observed in the
      phantom on initiation of cuff inflation with subsequent signal change being
      dependent on cuff pressure. Water peak linewidth increased linearly with cuff
      pressure (r(2) = 0.94). Aberrant T2* signal changes were observed in both the
      occluded and nonoccluded legs. CONCLUSION: Compressed air due to cuff inflation
      directly affects local magnetic field susceptibility. The T2* sequence is
      sensitive to local field disturbances induced by an inflated cuff. Muscle BOLD
      results are affected by high-pressure air, with a sudden drop in T2* signal being
      a characteristic feature of this induced effect.

PMID- 23172783
TI  - Estimating the intensity of ward admission and its effect on emergency department
      access block.
AB  - Emergency department access block is an urgent problem faced by many public
      hospitals today. When access block occurs, patients in need of acute care cannot
      access inpatient wards within an optimal time frame. A widely held belief is that
      access block is the end product of a long causal chain, which involves poor
      discharge planning, insufficient bed capacity, and inadequate admission intensity
      to the wards. This paper studies the last link of the causal chain-the effect of
      admission intensity on access block, using data from a metropolitan hospital in
      Australia. We applied several modern statistical methods to analyze the data.
      First, we modeled the admission events as a nonhomogeneous Poisson process and
      estimated time-varying admission intensity with penalized regression splines.
      Next, we established a functional linear model to investigate the effect of the
      time-varying admission intensity on emergency department access block. Finally,
      we used functional principal component analysis to explore the variation in the
      daily time-varying admission intensities. The analyses suggest that improving
      admission practice during off-peak hours may have most impact on reducing the
      number of ED access blocks.

PMID- 23172785
TI  - A new technique for fast and safe collection of urine in newborns.
AB  - AIM: To describe and test a new technique to obtain midstream urine samples in
      newborns. DESIGN AND METHODS: This was a prospective feasibility and safety study
      conducted in the neonatal unit of University Infanta Sofia Hospital, Madrid. A
      new technique based on bladder and lumbar stimulation manoeuvres was tested over
      a period of 4 months in 80 admitted patients aged less than 30 days. The main
      variable was the success rate in obtaining a midstream urine sample within 5 min.
      Secondary variables were time to obtain the sample and complications. RESULTS:
      This technique was successful in 86.3% of infants. Median time to sample
      collection was 45 s (IQR 30). No complications other than controlled crying were
      observed. CONCLUSIONS: A new, quick and safe technique with a high success rate
      is described, whereby the discomfort and waste of time usually associated with
      bag collection methods can be avoided.

PMID- 23172784
TI  - Season of birth in a nationwide cohort of coeliac disease patients.
AB  - BACKGROUND AND OBJECTIVE: Genetic factors alone cannot explain the risk of
      developing coeliac disease (CD). Children born in summer months are likely to be
      weaned and introduced to gluten during winter when viral infections are more
      frequent. Earlier studies on birth season and CD are limited in sample size and
      results are contradictory. METHOD: Case-control study. We used biopsy reports
      from all 28 Swedish pathology departments to identify individuals with CD,
      defined as small intestinal villous atrophy (n=29 096). The government agency
      Statistics Sweden then identified 144 522 controls matched for gender, age,
      calendar year and county. Through conditional logistic regression we examined the
      association between summer birth (March-August) and later CD diagnosis (outcome
      measure). RESULTS: Some 54.10% of individuals with CD versus 52.75% of controls
      were born in the summer months. Summer birth was hence associated with a small
      increased risk of later CD (OR 1.06; 95% CI 1.03 to 1.08; p<0.0001). Stratifying
      CD patients according to age at diagnosis, we found the highest OR in those
      diagnosed before age 2 years (OR 1.17; 95% CI 1.10 to 1.26), while summer birth
      was not associated with a CD diagnosis in later childhood (age 2-18 years: OR
      1.02; 95% CI 0.97 to 1.08), but had a marginal effect on the risk of CD in
      adulthood (age >=18 years: OR 1.04; 95% CI 1.01 to 1.07). CONCLUSIONS: In this
      study, summer birth was associated with an increased risk of later CD, but the
      excess risk was small, and general infectious disease exposure early in life is
      unlikely to be a major cause of CD.

PMID- 23172786
TI  - Eating-related environmental factors in underweight eating disorders and obesity:
      are there common vulnerabilities during childhood and early adolescence?
AB  - OBJECTIVE: This study aimed to examine whether there is an association between
      individual, social and family influences and dysfunctional eating patterns early
      in life and the likelihood of developing a subsequent underweight eating disorder
      (ED) or obesity. METHOD: The total sample comprised 152 individuals (underweight
      ED, n = 45; obese patients, n = 65; healthy controls; n = 42) from Barcelona,
      Spain. The Cross-Cultural Questionnaire (CCQ) was used to assess early eating
      influences as well as individual and family eating patterns and attitudes towards
      food. RESULTS: Even though a few shared eating influences emerged for both
      groups, unique factors were also observed. Whereas relationship with friends,
      teasing about eating habits by family members and the mass media were of specific
      relevance to the underweight ED group, the patient's own physical appearance,
      body dissatisfaction, teasing about eating habits by friends, teasing about body
      shape by family members and dysfunctional eating patterns were unique to obesity.
      CONCLUSIONS: Overlapping environmental risk factors provide evidence for integral
      prevention and intervention approaches that simultaneously tackle a range of
      weight-related problems. The unique factors might be important for targeting high
      risk individuals.

PMID- 23172787
TI  - Selenium levels in patients with hepatitis C virus-related chronic hepatitis,
      liver cirrhosis, and hepatocellular carcinoma: a pilot study.

PMID- 23172788
TI  - Reversible phase transformation and luminescence of cadmium(II)-dipyridylamide
      based coordination frameworks.
AB  - We have synthesized a series of 1D double-zigzag
      ({[Cd(paps)(2)(H(2)O)(2)](ClO(4))(2)}(n) (1),
      {[Cd(papo)(2)(H(2)O)(2)](ClO(4))(2)}(n) (3), and
      {[Cd(papc)(2)(H(2)O)(2)](ClO(4))(2)}(n) (5)) and 2D polyrotaxane frameworks
      ([Cd(papc)(2)(ClO(4))(2)](n) (6)) by the reaction of Cd(ClO(4))(2) with
      dipyridylamide ligands N,N'-bis(pyridylcarbonyl)-4,4'-diaminodiphenyl thioether
      (paps), N,N'-bis(pyridylcarbonyl)-4,4'-diaminodiphenyl ether (papo), and N,N'
      (methylenedi-p-phenylene)bispyridine-4-carboxamide (papc), respectively, where
      their molecular structures have been determined by X-ray diffraction studies.
      Based on the powder X-ray data (PXRD) of compound 3 and its Zn(II) analogue,
      heating the double-zigzag framework of compound 3 can give the polyrotaxane
      framework of [Cd(papo)(2)(ClO(4))(2)](n) (4) and grinding this powder sample in
      the presence of moisture resulted in its complete conversion back into the pure
      double-zigzag framework. In addition, heating the double-zigzag frameworks of
      compounds 1 and 5 can induce structural transformation into their respective
      polyrotaxanes, whereas grinding these solid samples in the presence of moisture
      did not lead to the formation of the double zigzags. Herein, we investigated the
      effect of the metal (from Zn(II) to Cd(II)) on the assembly process and
      luminescence properties, as well as on the particularly intriguing structural
      transformation of a series of papx-based frameworks. In fact, the assembly
      behavior and luminescence properties of the Cd(II)-papx and Zn(II)-papx
      frameworks were really similar. However, both Zn(II)-papx (x = s, o) frameworks
      can perform reversible structural transformation, but only the Cd(II)-papo
      framework can do it. Therefore, a delicate metal effect on such a new structural
      transformation can be observed.

PMID- 23172789
TI  - Is DARTEL-based voxel-based morphometry affected by width of smoothing kernel and
      group size? A study using simulated atrophy.
AB  - PURPOSE: To quantify to what extent the new registration method, DARTEL
      (Diffeomorphic Anatomical Registration Through Exponentiated Lie Algebra), may
      reduce the smoothing kernel width required and investigate the minimum group size
      necessary for voxel-based morphometry (VBM) studies. MATERIALS AND METHODS: A
      simulated atrophy approach was employed to explore the role of smoothing kernel,
      group size, and their interactions on VBM detection accuracy. Group sizes of 10,
      15, 25, and 50 were compared for kernels between 0-12 mm. RESULTS: A smoothing
      kernel of 6 mm achieved the highest atrophy detection accuracy for groups with 50
      participants and 8-10 mm for the groups of 25 at P < 0.05 with familywise
      correction. The results further demonstrated that a group size of 25 was the
      lower limit when two different groups of participants were compared, whereas a
      group size of 15 was the minimum for longitudinal comparisons but at P < 0.05
      with false discovery rate correction. CONCLUSION: Our data confirmed DARTEL-based
      VBM generally benefits from smaller kernels and different kernels perform best
      for different group sizes with a tendency of smaller kernels for larger groups.
      Importantly, the kernel selection was also affected by the threshold applied.
      This highlighted that the choice of kernel in relation to group size should be
      considered with care.

PMID- 23172790
TI  - Olig2-lineage cells preferentially differentiate into oligodendrocytes but their
      processes degenerate at the chronic demyelinating stage of proteolipid protein
      overexpressing mouse.
AB  - In chronic demyelinating lesions of the central nervous system, insufficient
      generation of oligodendrocytes (OLs) is not due to a lack of oligodendrocyte
      precursor cells (OPCs), because the accumulation of OPCs and premyelinating OLs
      can be observed within these lesions. Here we sought to identify the basis for
      the failure of OLs to achieve terminal differentiation in chronic demyelinating
      lesions through the utilization of plp1-overexpressing (Plp(tg/-)) mice. These
      mice are characterized by progressive demyelination in young adults and chronic
      demyelinating lesions at more mature stages. We show that neural stem cells,
      which are the precursors of OL-lineage cells, are present in the Plp(tg/-) mouse
      brain and that their multipotentiality and ability to self-renew are comparable
      to those of wild-type adults in culture. Lineage-tracing experiments using a
      transgenic mouse line, in which an inducible Cre recombinase is knocked in at the
      Olig2 locus, revealed that Olig2-lineage cells preferentially differentiated into
      OPCs and premyelinating OLs, but not into astrocytes, in the Plp(tg/-) mouse
      brain. These Olig2-lineage cells matured to express myelin basic protein but
      after that their processes degenerated in the chronic demyelinating lesions of
      the Plp(tg/-) brain. These results indicate that in chronic demyelinated lesions
      more OL-lineage cells are produced as part of the repair process, but their
      processes degenerate after maturation.

PMID- 23172791
TI  - Operant self-administration of a sigma ligand improves nociceptive and emotional
      manifestations of neuropathic pain.
AB  - BACKGROUND: The treatment of neuropathic pain is unsatisfactory at the present
      moment and the sigma 1 receptor has been identified as a new potential target for
      neuropathic pain. The aim of this study was to use an operant self-administration
      model to reveal the potential interest of a new sigma 1 receptor antagonist,
      S1RA, in chronic pain that was developed in mice by a partial ligation of the
      sciatic nerve. METHODS: Once that chronic pain had reached a steady state, mice
      were trained to maintain an operant behaviour to self-administer S1RA. The
      possible abuse liability of the analgesic compound was determined by evaluating
      operant self-administration in sham-operated mice. The influence of S1RA on the
      anhedonic state related to chronic pain was also evaluated by measuring the
      preference for palatable drink (2% sucrose solution) using a recently validated
      and highly sensitive behavioural device. RESULTS: Nerve-injured mice, but not
      sham-operated animals, acquired the operant responding to obtain S1RA (6
      mg/kg/infusion). After 10 days of S1RA self-administration, neuropathic pain was
      significantly reduced in nerve-injured mice. In addition, an anhedonic state was
      revealed in nerve-injured mice by a decreased consumption of palatable drink,
      which was significantly attenuated by S1RA (25 mg/kg). CONCLUSIONS: These results
      reveal the analgesic efficacy of the sigma antagonist, S1RA, in neuropathic pain
      associated with an improvement of the emotional negative state and that was
      devoided of reinforcing effects. The operant responses evaluated in this new
      mouse model can have a high predictive value to estimate the clinical
      benefit/risk ratio of new analgesic compounds to treat chronic pain, such as
      S1RA.

PMID- 23172792
TI  - Additive manufacturing techniques for the production of tissue engineering
      constructs.
AB  - 'Additive manufacturing' (AM) refers to a class of manufacturing processes based
      on the building of a solid object from three-dimensional (3D) model data by
      joining materials, usually layer upon layer. Among the vast array of techniques
      developed for the production of tissue-engineering (TE) scaffolds, AM techniques
      are gaining great interest for their suitability in achieving complex shapes and
      microstructures with a high degree of automation, good accuracy and
      reproducibility. In addition, the possibility of rapidly producing tissue
      engineered constructs meeting patient's specific requirements, in terms of tissue
      defect size and geometry as well as autologous biological features, makes them a
      powerful way of enhancing clinical routine procedures. This paper gives an
      extensive overview of different AM techniques classes (i.e. stereolithography,
      selective laser sintering, 3D printing, melt-extrusion-based techniques,
      solution/slurry extrusion-based techniques, and tissue and organ printing)
      employed for the development of tissue-engineered constructs made of different
      materials (i.e. polymeric, ceramic and composite, alone or in combination with
      bioactive agents), by highlighting their principles and technological solutions.

PMID- 23172793
TI  - Small-for-size syndrome and transjugular intrahepatic portosystemic shunt.

PMID- 23172794
TI  - Multilattice sampling strategies for region of interest dynamic MRI.
AB  - A multilattice sampling approach is proposed for dynamic MRI with Cartesian
      trajectories. It relies on the use of sampling patterns composed of several
      different lattices and exploits an image model where only some parts of the image
      are dynamic, whereas the rest is assumed static. Given the parameters of such an
      image model, the methodology followed for the design of a multilattice sampling
      pattern adapted to the model is described. The multi-lattice approach is compared
      to single-lattice sampling, as used by traditional acceleration methods such as
      UNFOLD (UNaliasing by Fourier-Encoding the Overlaps using the temporal Dimension)
      or k-t BLAST, and random sampling used by modern compressed sensing-based
      methods. On the considered image model, it allows more flexibility and higher
      accelerations than lattice sampling and better performance than random sampling.
      The method is illustrated on a phase-contrast carotid blood velocity mapping MR
      experiment. Combining the multilattice approach with the KEYHOLE technique allows
      up to 12* acceleration factors. Simulation and in vivo undersampling results
      validate the method. Compared to lattice and random sampling, multilattice
      sampling provides significant gains at high acceleration factors.

PMID- 23172795
TI  - Cell and tissue microarray technologies for protein and nucleic acid expression
      profiling.
AB  - Tissue microarray (TMA) and cell microarray (CMA) are two powerful techniques
      that allow for the immunophenotypical characterization of hundreds of samples
      simultaneously. In particular, the CMA approach is particularly useful for
      immunophenotyping new stem cell lines (e.g., cardiac, neural, mesenchymal) using
      conventional markers, as well as for testing the specificity and the efficacy of
      newly developed antibodies. We propose the use of a tissue arrayer not only to
      perform protein expression profiling by immunohistochemistry but also to carry
      out molecular genetics studies. In fact, starting with several tissues or cell
      lines, it is possible to obtain the complete signature of each sample, describing
      the protein, mRNA and microRNA expression, and DNA mutations, or eventually to
      analyze the epigenetic processes that control protein regulation. Here we show
      the results obtained using the Galileo CK4500 TMA platform.

PMID- 23172796
TI  - Mapping of carboxypeptidase m in normal human kidney and renal cell carcinoma:
      expression in tumor-associated neovasculature and macrophages.
AB  - Although the kidney generally has been regarded as an excellent source of
      carboxypeptidase M (CPM), little is known about its renal-specific expression
      level and distribution. This study provides a detailed localization of CPM in
      healthy and diseased human kidneys. The results indicate a broad distribution of
      CPM along the renal tubular structures in the healthy kidney. CPM was identified
      at the parietal epithelium beneath the Bowman's basement membrane and in
      glomerular mesangial cells. Capillaries, podocytes, and most interstitial cells
      were CPM negative. Tumor cells of renal cell carcinoma subtypes lose CPM
      expression upon dedifferentiation. Tissue microarray analysis demonstrated a
      correlation between low CPM expression and tumor cell type. CPM staining was
      intense on phagocytotic tumor-associated macrophages. Immunoreactive CPM was also
      detected in the tumor-associated vasculature. The absence of CPM in normal renal
      blood vessels points toward a role for CPM in angiogenesis. Coexistence of CPM
      and the epidermal growth factor receptor (EGFR) was detected in papillary renal
      cell carcinoma. However, the different subcellular localization of CPM and EGFR
      argues against an interaction between these h proteins. The description of the
      distribution of CPM in human kidney forms the foundation for further study of the
      (patho)physiological activities of CPM in the kidney.

PMID- 23172797
TI  - Fibromyalgia family and relationship impact exploratory survey.
AB  - BACKGROUND: Fibromyalgia is frequently associated with impairments in activities
      of daily living and work disability. Limited data have investigated the impact of
      fibromyalgia on relationships with family and friends. OBJECTIVES: This
      exploratory study was designed to survey a large community sample of adults with
      fibromyalgia about the impact on the spouse/partner, children and close friends.
      METHODS: A 40-question, multiple-choice survey was made available online for a
      two-month period, with potential participants recruited through fibromyalgia and
      migraine community websites. Items included questions about demographics,
      fibromyalgia symptoms, comorbid mood disturbance and relationship impact,
      including the Relationship Assessment Scale. RESULTS: The survey was completed by
      6,126 adults who had been diagnosed with fibromyalgia. Using updated diagnostic
      criteria from the American College of Rheumatology, 91% satisfied the criteria
      for fibromyalgia (Fibromyalgia Severity score >=13 and pain >=3 months). Half of
      participants endorsed that fibromyalgia had mildly to moderately damaged
      relationship(s) with their spouse(s)/partner(s) or contributed to a break-up with
      a spouse or partner. Half of participants scored as not being satisfied with
      their current spouse/partner relationship, with satisfaction negatively affected
      by the presence of mood disturbance symptoms and higher fibromyalgia severity.
      Relationships with children and close friends were also negatively impacted for a
      substantial minority of participants. CONCLUSIONS: In addition to physical
      impairments that are well documented among individuals with fibromyalgia,
      fibromyalgia can result in a substantial negative impact on important
      relationships with family and close friends.

PMID- 23172798
TI  - Linking micro- and macro-evolution at the cell type level: a view from the
      lophotrochozoan Platynereis dumerilii.
AB  - Ever since the origin of the first metazoans over 600 million years ago, cell
      type diversification has been driven by micro-evolutionary processes at
      population level, leading to macro-evolution changes above species level. In this
      review, we introduce the marine annelid Platynereis dumerilii, a member of the
      lophotrochozoan clade (a key yet most understudied superphylum of bilaterians),
      as a suitable model system for the simultaneous study, at cellular resolution, of
      macro-evolutionary processes across phyla and of micro-evolutionary processes
      across highly polymorphic populations collected worldwide. Recent advances in
      molecular and experimental techniques, easy maintenance and breeding, and the
      fast, synchronous and stereotypical development have facilitated the
      establishment of Platynereis as one of the leading model species in the eco-evo
      devo field. Most importantly, Platynereis allows the combination of expression
      profiling, morphological and physiological characterization at the single cell
      level. Here, we discuss recent advances in the collection of -omics data for the
      lab strain and for natural populations collected world-wide that can be
      integrated with population-specific cellular analyses to result in a cellular
      atlas integrating genetic, phenotypic and ecological variation. This makes
      Platynereis a tractable system to begin understanding the interplay between macro
      and micro-evolutionary processes and cell type diversity. 

PMID- 23172799
TI  - Reproducibility of hepatic fat fraction measurement by magnetic resonance
      imaging.
AB  - PURPOSE: To evaluate the reproducibility of magnetic resonance imaging (MRI)
      determined hepatic fat fraction (%) across imaging sites with different magnet
      types and field strength. Reproducibility among MRI platforms is unclear, even
      though evaluating hepatic fat fractions (FFs) using MRI-based methods is accurate
      against MR spectroscopy. MATERIALS AND METHODS: Overweight subjects were
      recruited to undergo eight MRI examinations at five imaging centers with a range
      of magnet manufacturers and field strengths (1.5 and 3 T). FFs were estimated in
      liver and in fat-emulsion phantoms using three methods: 1) dual-echo images
      without correction (nominally out-of-phase [OP] and in-phase [IP]); 2) dual-dual
      echo images (two sequences) with T2* correction (nominally OP/IP and IP/IP); and
      3) six-echo images with spectral model and T2* correction, at sequential
      alternating OP and IP echo times (Methods 1, 2, and 3, respectively). RESULTS:
      Ten subjects were recruited. For Methods 1, 2, and 3, respectively, hepatic FF
      ranged from -2.5 to 27.0, 1.9 to 29.6, and 1.3 to 34.4%. Intraclass correlation
      coefficients were 0.85, 0.89, and 0.91 for each method, and within-subject
      coefficients of variation were 18.5, 9.9, and 10.3%, respectively. Mean phantom
      FFs derived by Methods 2 and 3 were comparable to the known FF for each phantom.
      Method 1 underestimated phantom FF. CONCLUSION: Methods 2 and 3 accurately assess
      FF. Strong reproducibility across magnet type and strength render them suitable
      for use in multicenter trials and longitudinal assessments.

PMID- 23172800
TI  - Sodium L-lactate differently affects brain-derived neurothrophic factor,
      inducible nitric oxide synthase, and heat shock protein 70 kDa production in
      human astrocytes and SH-SY5Y cultures.
AB  - The present study analyzed the in vitro effects induced by sodium L-lactate on
      human astrocytes and the SH-SY5Y cell line, when added at concentrations of 5,
      10, and 25 mmol/liter. Expression of brain-derived neurotrophic factor (BDNF),
      inducible nitric oxide synthase (iNOS), and heat shock protein 70 kDa (HSP70) was
      evaluated by Western blot analysis. Cell viability with MTT, release of nitric
      oxide (NO) through the Griess reaction, and production of BDNF by enzyme-linked
      immunoassay was determined. Data indicate that, in SH-SY5Y as well as in cortical
      astrocytes, after 4 hr sodium L-lactate increases the expression and release of
      BDNF, iNOS, and NO; after 24 hr, it turns is ineffective for the production of
      the neurotrophin in SH-SY5Y and not in astrocytes, but the expression of iNOS and
      release of NO appear to be further increased compared with those after 4 hr.
      Sodium L-lactate influences differently the expression of HSP70 in SH-SY5Y
      compared with astrocytes. We propose, based on these findings, that sodium L
      lactate affects the expression of BDNF in SH-SY5Y and astrocytes in a different
      manner: high levels of iNOS and NO expressed in SH-SY5Y have a profound
      inhibitory effect on the release of BDNF related to a more limited production of
      HSP70 by SH-SY5Y. In conclusion, the results demonstrate differences in the
      responses of SH-SY5Y and astrocytes to stimulation by high levels of sodium L
      lactate. Sodium L-lactate differently and dose and time dependently influences
      the expression and release of BDNF, iNOS, NO, and HSP70 depending on the cell
      type.

PMID- 23172801
TI  - Stable five-coordinate silicon(IV) complexes with SiN4 X skeletons (X = S, Se,
      Te) and Si=X double bonds.
AB  - Silylenes: Reaction of the donor-stabilized silylene 1 with elemental sulfur,
      selenium, or tellurium led to the formation of 2 a-c [SiN(4)X skeletons (X = S,
      Se, Te)], the first stable five-coordinate silicon(IV) compounds with silicon
      chalcogen double bonds (see figure).

PMID- 23172803
TI  - Penile urethra replacement with autologous cell-seeded tubularized collagen
      matrices.
AB  - Acellular collagen matrices have been used as an onlay material for urethral
      reconstruction. However, cell-seeded matrices have been recommended for
      tubularized urethral repairs. In this study we investigated whether long
      segmental penile urethral replacement using autologous cell-seeded tubularized
      collagen-based matrix is feasible. Autologous bladder epithelial and smooth
      muscle cells from nine male rabbits were grown and seeded onto preconfigured
      tubular matrices constructed from decellularized bladder matrices obtained from
      lamina propria. The entire anterior penile urethra was resected in 15 rabbits.
      Urethroplasties were performed with tubularized matrices seeded with cells in
      nine animals, and with matrices without cells in six. Serial urethrograms were
      performed at 1, 3 and 6 months. Retrieved urethral tissues were analysed using
      histo- and immunohistochemistry, western blot analyses and organ bath studies.
      The urethrograms showed that animals implanted with cell-seeded matrices
      maintained a wide urethral calibre without strictures. In contrast, the urethras
      with unseeded scaffolds collapsed and developed strictures. Histologically, a
      transitional cell layer surrounded by muscle was observed in the cell-seeded
      constructs. The epithelial and smooth muscle phenotypes were confirmed with
      AE1/AE3 and alpha-actin antibodies. Organ bath studies of the neourethras
      confirmed both physiological contractility and the presence of neurotransmitters.
      Tubularized collagen matrices seeded with autologous cells can be used
      successfully for long segmental penile urethra replacement, while implantation of
      tubularized collagen matrices without cells leads to poor tissue development and
      stricture formation. The cell-seeded collagen matrices are able to form new
      tissue, which is histologically similar to native urethra.

PMID- 23172804
TI  - Reducing the thickness of left lateral segment grafts in neonatal living donor
      liver transplantation.
AB  - Liver transplantation is now an established treatment for children with end-stage
      liver disease. Left lateral segment (LLS) grafts are most commonly used in split
      and living donor liver transplantation in children. In very small children, LLS
      grafts can be too large, and further nonanatomical reduction has recently been
      introduced to mitigate the problem of large-for-size grafts. However, the
      implantation of LLS grafts can be a problem in infants and very small children
      because of the thickness of the grafts, and these techniques do not address
      problems related to thickness. We herein describe a technique for reducing the
      thickness of living donor left lateral grafts and successful transplantation in a
      2.8-kg infant with acute liver failure.

PMID- 23172805
TI  - Noncontrast-enhanced renal angiography using multiple inversion recovery and
      alternating TR balanced steady-state free precession.
AB  - Noncontrast-enhanced renal angiography techniques based on balanced steady-state
      free precession avoid external contrast agents, take advantage of high inherent
      blood signal from the T 2 / T 1 contrast mechanism, and have short steady-state
      free precession acquisition times. However, background suppression is limited;
      inflow times are inflexible; labeling region is difficult to define when tagging
      arterial flow; and scan times are long. To overcome these limitations, we propose
      the use of multiple inversion recovery preparatory pulses combined with
      alternating pulse repetition time balanced steady-state free precession to
      produce renal angiograms. Multiple inversion recovery uses selective spatial
      saturation followed by four nonselective inversion recovery pulses to
      concurrently null a wide range of background T 1 species while allowing for
      adjustable inflow times; alternating pulse repetition time steady-state free
      precession maintains vessel contrast and provides added fat suppression. The high
      level of suppression enables imaging in three-dimensional as well as projective
      two-dimensional formats, the latter of which has a scan time as short as one
      heartbeat. In vivo studies at 1.5 T demonstrate the superior vessel contrast of
      this technique.

PMID- 23172806
TI  - Apoptosis induced by para-phenylenediamine involves formation of ROS and
      activation of p38 and JNK in chang liver cells.
AB  - para-Phenylenediamine (p-PD) is a suspected carcinogen, but it has been widely
      used as a component in permanent hair dyes. In this study, the mechanism of p-PD
      induced cell death in normal Chang liver cells was investigated. The results
      demonstrated that p-PD decreased cell viability in a dose-dependent manner. Cell
      death via apoptosis was confirmed by enhanced DNA damage and increased cell
      number in the sub-G1 phase of the cell cycle, using Hoechst 33258 dye staining
      and flow cytometry analysis. Apoptosis via reactive oxygen species generation was
      detected by the dichlorofluorescin diacetate staining method. Mitogen-activated
      protein kinase (MAPK) activation was assessed by western blot analysis and
      revealed that p-PD activated not only stress-activated protein kinase (SAPK)/c
      Jun N-terminal kinases (JNK) and p38 MAPK but also extracellular signal-regulated
      kinase (ERK). Cytotoxicity and apoptosis induced by p-PD were markedly enhanced
      by ERK activation and selectively inhibited by ERK inhibitor PD98059, thus
      indicating a negative role of ERK. In contrast, inhibition of p38 MAPK activity
      with the p38-specific inhibitor SB203580 moderately inhibited cytotoxicity and
      apoptosis induction by p-PD. Similarly, SP600125, an inhibitor of SAPK/JNK,
      moderately inhibited cytotoxicity and apoptosis induced by p-PD, thus implying
      that p38 MAPK and SAPK/JNK had a partial role in p-PD-induced apoptosis. Western
      blot analysis revealed that p-PD significantly increased phosphorylation of p38
      and SAPK/JNK and decreased phosphorylation of ERK. In conclusion, the results
      demonstrated that SAPK/JNK and p38 cooperatively participate in apoptosis induced
      by p-PD and that a decreased ERK signal contributes to growth inhibition or
      apoptosis.

PMID- 23172807
TI  - Correction of eddy current distortions in high angular resolution diffusion
      imaging.
AB  - PURPOSE: To correct distortions caused by eddy currents induced by large
      diffusion gradients during high angular resolution diffusion imaging without any
      auxiliary reference scans. MATERIALS AND METHODS: Image distortion parameters
      were obtained by image coregistration, performed only between diffusion-weighted
      images with close diffusion gradient orientations. A linear model that describes
      distortion parameters (translation, scale, and shear) as a function of diffusion
      gradient directions was numerically computed to allow individualized distortion
      correction for every diffusion-weighted image. RESULTS: The assumptions of the
      algorithm were successfully verified in a series of experiments on phantom and
      human scans. Application of the proposed algorithm in high angular resolution
      diffusion images markedly reduced eddy current distortions when compared to
      results obtained with previously published methods. CONCLUSION: The method can
      correct eddy current artifacts in the high angular resolution diffusion images,
      and it avoids the problematic procedure of cross-correlating images with
      significantly different contrasts resulting from very different gradient
      orientations or strengths.

PMID- 23172809
TI  - Reconciliation of metabolites and biochemical reactions for metabolic networks.
AB  - Genome-scale metabolic network reconstructions are now routinely used in the
      study of metabolic pathways, their evolution and design. The development of such
      reconstructions involves the integration of information on reactions and
      metabolites from the scientific literature as well as public databases and
      existing genome-scale metabolic models. The reconciliation of discrepancies
      between data from these sources generally requires significant manual curation,
      which constitutes a major obstacle in efforts to develop and apply genome-scale
      metabolic network reconstructions. In this work, we discuss some of the major
      difficulties encountered in the mapping and reconciliation of metabolic resources
      and review three recent initiatives that aim to accelerate this process, namely
      BKM-react, MetRxn and MNXref (presented in this article). Each of these resources
      provides a pre-compiled reconciliation of many of the most commonly used
      metabolic resources. By reducing the time required for manual curation of
      metabolite and reaction discrepancies, these resources aim to accelerate the
      development and application of high-quality genome-scale metabolic network
      reconstructions and models. 

PMID- 23172810
TI  - An "against the rules" double bank shot with diisobutylaluminum hydride to allow
      triple functionalization of alpha-cyclodextrin.
AB  - Frustration leads to overreaction: when diametrically opposed regioselective
      debenzylation is frustrated, an unexpected double debenzylation reaction affords
      original tetrafunctionalized cyclodextrins in a controlled and efficient manner.
      A rationale of the reaction is proposed based on a kinetic study.

PMID- 23172808
TI  - Upregulation of brain-derived neurotrophic factor expression in nodose ganglia
      and the lower brainstem of hypertensive rats.
AB  - Hypertension leads to structural and functional changes at baroreceptor synapses
      in the medial nucleus tractus solitarius (NTS), but the underlying molecular
      mechanisms remain unknown. Our previous studies show that brain-derived
      neurotrophic factor (BDNF) is abundantly expressed by rat nodose ganglion (NG)
      neurons, including baroreceptor afferents and their central terminals in the
      medial NTS. We hypothesized that hypertension leads to upregulation of BDNF
      expression in NG neurons. To test this hypothesis, we used two mechanistically
      distinct models of hypertension, the spontaneously hypertensive rat (SHR) and the
      deoxycorticosterone acetate (DOCA)-salt rat. Young adult SHRs, whose blood
      pressure was significantly elevated compared with age-matched Wistar-Kyoto (WKY)
      control rats, exhibited dramatic upregulation of BDNF mRNA and protein in the NG.
      BDNF transcripts from exon 4, known to be regulated by activity, and exon 9
      (protein-coding region) showed the largest increases. Electrical stimulation of
      dispersed NG neurons with patterns that mimic baroreceptor activity during blood
      pressure elevations led to increases in BDNF mRNA that were also mediated through
      promoter 4. The increase in BDNF content of the NG in vivo was associated with a
      significant increase in the percentage of BDNF-immunoreactive NG neurons.
      Moreover, upregulation of BDNF in cell bodies of NG neurons was accompanied by a
      significant increase in BDNF in the NTS region, the primary central target of NG
      afferents. A dramatic increase in BDNF in the NG was also detected in DOCA-salt
      hypertensive rats. Together, our study identifies BDNF as a candidate molecular
      mediator of activity-dependent changes at baroafferent synapses during
      hypertension.

PMID- 23172816
TI  - Design and characterization of a tissue-engineered bilayer scaffold for
      osteochondral tissue repair.
AB  - Treatment of full-thickness cartilage defects relies on osteochondral bilayer
      grafts, which mimic the microenvironment and structure of the two affected
      tissues: articular cartilage and subchondral bone. However, the integrity and
      stability of the grafts are hampered by the presence of a weak interphase,
      generated by the layering processes of scaffold manufacturing. We describe here
      the design and development of a bilayer monolithic osteochondral graft, avoiding
      delamination of the two distinct layers but preserving the cues for selective
      generation of cartilage and bone. A highly porous polycaprolactone-based graft
      was obtained by combining solvent casting/particulate leaching techniques. Pore
      structure and interconnections were designed to favour in vivo vascularization
      only at the bony layer. Hydroxyapatite granules were added as bioactive signals
      at the site of bone regeneration. Unconfined compressive tests displayed optimal
      elastic properties and low residual deformation of the graft after unloading (<
      3%). The structural integrity of the graft was successfully validated by tension
      fracture tests, revealing high resistance to delamination, since fractures were
      never displayed at the interface of the layers (n = 8). Ectopic implantation of
      grafts in nude mice, after seeding with bovine trabecular bone-derived
      mesenchymal stem cells and bovine articular chondrocytes, resulted in thick areas
      of mature bone surrounding ceramic granules within the bony layer, and a
      cartilaginous alcianophilic matrix in the chondral layer. Vascularization was
      mostly observed in the bony layer, with a statistically significant higher blood
      vessel density and mean area. Thus, the easily generated osteochondral scaffolds,
      since they are mechanically and biologically functional, are suitable for tissue
      engineering applications for cartilage repair.

PMID- 23172817
TI  - Self-reported oral symptoms and signs in liver transplant recipients and a
      control population.
AB  - Recipients of liver transplantation (LT) receive lifelong immunosuppression,
      which causes side effects. We investigated self-reported oral symptoms and
      associated risk factors with the following hypothesis: symptoms and signs would
      differ between LT recipients of different etiology groups and also between LT
      recipients and a control population. Eighty-four LT recipients (64 with chronic
      liver disease and 20 with acute liver disease) were recruited for clinical oral
      and salivary examinations (median follow-up = 5.7 years). A structured
      questionnaire was used to record subjective oral symptoms. Matched controls (n =
      252) came from the National Finnish Health 2000 survey. The prevalence of
      symptoms was compared between the groups, and the risk factors for oral symptoms
      were analyzed. Xerostomia was prevalent in 48.4% of the chronic LT recipients and
      in 42.1% of the acute LT recipients. This subjective feeling of dry mouth was
      only partly linked to objectively measured hyposalivation. The chronic transplant
      recipients had significantly lower unstimulated salivary flow rates than the
      acute transplant recipients (0.34 +/- 0.31 versus 0.61 +/- 0.49 mL/minute, P =
      0.005). Among the chronic transplant recipients, hyposalivation with unstimulated
      salivary flow was associated with fewer teeth (17.7 +/- 8.2 versus 21.9 +/- 8.4,
      P = 0.047) and more dentures (33.3% versus 12.2%, P = not significant). The
      chronic patients reported significantly more dysphagia than their controls (23.4%
      versus 11.5%, P = 0.02). Increases in the number of medications increased the
      symptoms in all groups. In conclusion, dysphagia was significantly more prevalent
      among the chronic LT recipients versus the controls. The number of medications
      was a risk factor for dry mouth-related symptoms for both the LT recipients and
      the controls. The chronic transplant recipients presented with lower salivary
      flow rates than the acute transplant recipients. Hyposalivation correlated with
      generally worse oral health among the chronic transplant recipients. These
      differences between the chronic and acute LT recipients may have been due to
      differences in their medical conditions due to the different etiologies.

PMID- 23172818
TI  - Exposure to bifenthrin causes immunotoxicity and oxidative stress in male mice.
AB  - Bifenthrin (BF) is one of the most commonly used pesticides among the synthetic
      pyrethroids. The effects of BF exposure on the induction of immunotoxicity and
      oxidative stress were studied both in adolescent and adult male ICR mice. Both
      the weights of the spleen and thymus decreased significantly in the adolescent
      mice when they were treated with 20 mg/kg BF for 3 weeks. We found that the 3
      week oral administration of BF during puberty increased the transcriptional
      levels of the genes TNF and IL2 in the spleen and IL2 as well as IL4 in the
      thymus. The effect of BF exposure on the induction of oxidative stress was also
      studied in serum and liver samples. The total antioxidant capacity and activity
      of superoxide dismutase were altered significantly in the serum of the 20 mg/kg
      BF-treated adolescent mice, and the activity of glutathione peroxidase (GPX)
      decreased significantly in the serum of adolescent and adult mice after 3 weeks
      of oral administration of 20 mg/kg BF. Compared to serum, hepatic GSH content
      increased significantly in both the adolescent and adult mice exposed to 20 mg/kg
      BF; hepatic CAT and GPX activities were altered significantly, even in adolescent
      mice, after treatment with 10 mg/kg BF. Taken together, the results of this study
      suggest that exposure to BF, especially during puberty, has the potential to
      induce immunotoxicity accompanied by oxidative stress in male mice. These
      findings will help in elucidating the mechanism of toxicity induced by BF in
      mice.

PMID- 23172819
TI  - Intravoxel incoherent motion imaging of focal hepatic lesions.
AB  - PURPOSE: To compare diffusivity values between malignant and benign focal hepatic
      lesions using the intravoxel incoherent motion model. MATERIALS AND METHODS: This
      study included 84 focal hepatic lesions in 84 patients. Final diagnoses were as
      follows: hepatocellular carcinoma (n = 45), cholangiocarcinoma (n = 6),
      metastatic liver tumor (n = 3), cyst (n = 20), hemangioma (n = 5), inflammatory
      pseudotumor (n = 2), abscess (n = 2), and focal nodular hyperplasia (n = 1).
      Diffusion-weighted images at 12 b-values were used to obtain the diffusion
      coefficient of pure molecular diffusion (D), diffusion coefficient of
      microcirculation or perfusion-related diffusion (D*), and perfusion-related
      diffusion fraction (f). Parameters of malignant and benign focal hepatic lesions
      were compared using the Wilcoxon test. The diagnostic performance for
      distinguishing between malignant and benign hepatic lesions was also analyzed.
      RESULTS: Both the D value (1.15 +/- 0.21 * 10(-3) mm(2) /s [mean +/- standard
      deviation]) and D* value (62.7 +/- 12.7 * 10(-3) mm(2) /s) in malignant lesions
      was significantly lower than that in benign lesions (D value [2.46 +/- 0.45* 10(
      3) mm(2) /s], P < 0.0001; D* value [87.6 +/- 35.3 * 10(-3) mm(2) /s], P =
      0.0008). The f value did not differ significantly between malignant (25.0 15.1 +/
      15.1%) and benign lesions (30.1 +/- 16.3%). CONCLUSION: D* and D values were
      suppressed in malignant lesions. However, the D value was more reliable for
      distinguishing between malignant and benign focal hepatic lesions.

PMID- 23172820
TI  - Elevated serum haptoglobin after traumatic brain injury is synthesized mainly in
      liver.
AB  - Haptoglobin (Hp), an acute-phase response protein, is typically increased in the
      serum of adults after acute tissue injury. It is an antioxidant and may function
      as an injury-induced neuroprotective protein. However, the source of increased Hp
      is not clear. To investigate its source, we compared its time course expression
      profile in serum from rats with or without traumatic brain injury (TBI). Elevated
      Hp levels revealed by proteomic analysis were confirmed by Western blot,
      semiquantitative PCR, and real-time PCR. We found that Hp protein and mRNA levels
      were increased after TBI in both serum and liver, especially in liver. Both in
      vivo and in vitro data showed that Hp expression was increased in rat and human
      (HL7702) liver cells upon treatment with TBI serum. Addition of anti-interleukin
      6 (IL-6) antibody downregulated the expression of Hp in liver cells induced by
      serum derived from rats and in liver of rats after TBI. These findings suggest
      that the increased Hp in serum came from the liver in response to TBI and that IL
      6 is an important mediator of this induction.

PMID- 23172821
TI  - Reversible photochemically gated transformation of a hemicarcerand to a
      carcerand.
AB  - Guests in a gated community: introduction of two anthracene groups into a linker
      in a hemicarcerand creates a new type of photochemically controlled gated
      hemicarcerand. The reversible opening and closing of the "gate" of the host is
      controlled photochemically. The encapsulation and release of the guest molecules
      such as 1,4-dimethoxybenzene is controlled by irradiation with light of different
      wavelengths.

PMID- 23172822
TI  - Staged release of bilateral carpal tunnel syndrome: cancellation rates of the
      second side procedure.

PMID- 23172823
TI  - Neutrophilic dermatosis: a rare cause of an ischaemic digit.

PMID- 23172824
TI  - Dewaxed ECM: A simple method for analyzing cell behaviour on decellularized
      extracellular matrices.
AB  - Decellularization techniques have been used on a wide variety of tissues to
      create cell-seedable scaffolds for tissue engineering. Finding a suitable
      decellularization protocol for a certain type of tissue can be laborious,
      especially when organ perfusion devices are needed. In this study, we report a
      quick and simple method for comparing decellularization protocols combining the
      use of paraffin slices and two-dimensional cell cultures. We developed three
      decellularization protocols for adult murine kidney that yielded decellularized
      extracellular matrices (ECMs) with varying histological properties. The resulting
      paraffin-embedded ECM slices were deparaffinized and reseeded with murine
      embryonic stem cells (mESCs). We analyzed cell attachment four days post seeding
      via determination of cell numbers, and used quantitative Real-Time PCR 13 days
      post seeding to measure gene expression levels of two genes associated with renal
      development, Pax2 and Pou3f3. The three decellularization protocols produced
      kidney-matrices that showed clearly distinguishable results. We demonstrated that
      formerly paraffin-embedded decellularized ECMs can effectively influence
      differentiation of stem cells. This method can be used to identify optimal
      decellularization protocols for recellularization of three-dimensional tissue
      scaffolds with embryonic stem cells and other tissue-specific cell types.

PMID- 23172825
TI  - Role of propolis (bee glue) in improving histopathological changes of the kidney
      of rat treated with aluminum chloride.
AB  - Humans are frequently exposed to aluminum from various food additives,
      therapeutic treatments and the environment, and it can be potentially toxic. This
      study is aimed to elucidate the protective effects of propolis against aluminum
      chloride (AlCl3 )-induced histopathological and immunohistochemical changes in
      kidney tissues of rats. Sixty Wistar Albino male rats (average weight 250-300 g)
      were divided into three equal groups. The first served as a negative control. The
      second received AlCl3 (34 mg/kg bw, 1/ 25 LD 50). The third were administered
      AlCl3 (34 mg/kg bw, 1/ 25 LD 50) plus propolis (50 mg/kg bw). Doses were given
      once daily via a gavage for 8 weeks every day. The results showed that shrunken
      glomeruli, intraglomerular congestion, loss of apical microvilli, degeneration of
      mitochondria and widened rough endoplasmic reticulum were also observed in the
      Proximal Convoluted Tubules of these animals. Treatment with propolis ameliorated
      the harmful effects of AlCl3 ; this was also proved histopathologically by the
      noticeable improvement in the renal tissues. There were also significant
      variations in the expressed of ki-67 and p53 proteins. It can be concluded that
      propolis may be promising as a natural therapeutic agent in AlCl3 -induced renal
      toxicity and oxidative stress in rat kidneys.

PMID- 23172827
TI  - Synthesis and pharmacological screening of novel meso-substituted porphyrin
      analogs.
AB  - A novel series of mesotetrakis[aryl]-21H,23H-porphyrin derivatives 2a-j was
      synthesized from the condensation of aldehyde derivatives 1a-j with pyrrole in
      the presence of p-toluenesulfonic acid. The synthesized porphyrins were
      considered as a model to study the free radical-induced damage of biological
      membranes and the protective effects of these porphyrins. It was found that these
      compounds effectively inhibit the free radical-induced oxidative hemolysis of red
      blood cells. Compounds 2c and 2d which bear a sulfur atom, a nitro group, and a
      chlorine atom exhibited markedly higher antihemolysis activity than the other
      analogous. Compounds 2a, 2c, 2d, and 2j showed the highest protection activity
      against DNA damage induced by the bleomycin-iron complex. Compounds 2d, 2f, 2i,
      and 2j were proved to exhibit antioxidative activity.

PMID- 23172826
TI  - Raf and PI3K are the molecular targets for the anti-metastatic effect of
      luteolin.
AB  - Metastases are the primary cause of human cancer deaths. Luteolin, a naturally
      occurring phytochemical, has chemopreventive and/or anticancer properties in
      several cancer cell lines. However, anti-metastatic effects of luteolin in vivo
      and the underlying molecular mechanisms and target(s) remain unknown. Luteolin
      suppresses matrix metalloproteinase (MMP)-2 and -9 activities and invasion in
      murine colorectal cancer CT-26 cells. Western blot and kinase assay data revealed
      that luteolin inhibited Raf and phosphatidylinositol 3-kinase (PI3K) activities
      and subsequently attenuated phosphorylation of MEK and Akt. A pull-down assay
      indicated that luteolin non-competitively bound with ATP to suppress Raf activity
      and competitively bound with ATP to inhibit PI3K activity. GW5074, a Raf
      inhibitor, and LY294002, a PI3K inhibitor, inhibited MMP-2 and -9 activities and
      invasion in CT-26 cells. An in vivo mouse study showed that oral administration
      (10 or 50 mg/kg) of luteolin significantly inhibited tumor nodules and tumor
      volume of lung metastasis induced by intravenous injection of CT-26 cells.
      Luteolin also inhibited MMP-9 expression and activity in CT-26-induced mouse lung
      tissue. These results suggest that luteolin may have considerable potential for
      development as an anti-metastatic agent.

PMID- 23172828
TI  - Magnetization exchange observed in human skeletal muscle by non-water-suppressed
      proton magnetic resonance spectroscopy.
AB  - Many metabolites in the proton magnetic resonance spectrum undergo magnetization
      exchange with water, such as those in the downfield region (6.0-8.5 ppm) and the
      upfield peaks of creatine, which can be measured to reveal additional information
      about the molecular environment. In addition, these resonances are attenuated by
      conventional water suppression techniques complicating detection and
      quantification. To characterize these metabolites in human skeletal muscle in
      vivo at 3 T, metabolite cycled non-water-suppressed spectroscopy was used to
      conduct a water inversion transfer experiment in both the soleus and tibialis
      anterior muscles. Resulting median exchange-independent T1 times for the creatine
      methylene resonances were 1.26 and 1.15 s, and for the methyl resonances were
      1.57 and 1.74 s, for soleus and tibialis anterior muscles, respectively.
      Magnetization transfer rates from water to the creatine methylene resonances were
      0.56 and 0.28 s(-1), and for the methyl resonances were 0.39 and 0.30 s(-1), with
      the soleus exhibiting faster transfer rates for both resonances, allowing
      speculation about possible influences of either muscle fibre orientation or
      muscle composition on the magnetization transfer process. These water
      magnetization transfer rates observed without water suppression are in good
      agreement with earlier reports that used either postexcitation water suppression
      in rats, or short CHESS sequences in human brain and skeletal muscle.

PMID- 23172829
TI  - Enzyme-encapsulating quantum dot hydrogels and xerogels as biosensors:
      multifunctional platforms for both biocatalysis and fluorescent probing.

PMID- 23172830
TI  - Influence of age and gender before and after liver transplantation.
AB  - Women constitute a particular group among patients with chronic liver disease and
      in the post-liver transplantation (LT) setting: they are set apart not only by
      traditional differences with respect to men (ie, body mass index, different
      etiologies of liver disease, and accessibility to transplantation) but also in
      increasingly evident ways related to hormonal changes that characterize first the
      fertile age and subsequently the postmenopausal period (eg, disease course
      variability and responses to therapy). The aim of this review is, therefore, to
      evaluate the role of the interplay of factors such as age, gender, and hormones
      in influencing the natural history of chronic liver disease before and after LT
      and their importance in determining outcomes after LT. As the population
      requiring LT ages and the mean age at transplantation increases, older females
      are being considered for transplantation. Older patients are at greater risk for
      nonalcoholic steatohepatitis, osteoporosis, and a worse response to antiviral
      therapy. Female gender per se is associated with a greater risk for osteoporosis
      because of metabolic changes after menopause, the bodily structure of females,
      and, in the population of patients with chronic liver disease, the greater
      prevalence of cholestatic and autoimmune liver diseases. With menopause, the fall
      of protective estrogen levels can lead to increased fibrosis progression, and
      this represents a negative turning point for women with chronic liver disease and
      especially for patients with hepatitis C. Therefore, the notion of gender as a
      binary female/male factor is now giving way to the awareness of more complex
      disease processes within the female gender that follow hormonal, social, and age
      patterns and need to be addressed directly and specifically.

PMID- 23172831
TI  - Enhanced fat suppression technique for breast imaging.
AB  - PURPOSE: To evaluate a new fat suppression technique using multiple fat
      suppression pulses intended for breast dynamic contrast-enhanced (DCE) imaging
      using segmented three-dimensional fast field echo (FFE). MATERIALS AND METHODS:
      The effect of multiple spectrally-selective fat suppression radiofrequency pulses
      was modeled using numerical Bloch-equation solutions for the following fat
      suppression techniques: spectral-selective inversion recovery (SPIR: one pulse),
      double fat suppression (DFS: two pulses, combining one SPIR pulse and one CHESS
      pulse), and triple fat suppression (TFS: three pulses, combining one SPIR pulse
      and two CHESS pulses). The simulation data were evaluated in terms of fat
      suppression performance, scan time, and specific absorption rate (SAR) relative
      to the SPIR technique. The DFS technique was selected as the optimal technique
      based on the efficacy of fat suppression versus the costs of scan time and SAR.
      The DFS technique was compared with SPIR in six volunteer studies using segmented
      T1 -weighted three-dimensional FFE. RESULTS: The DFS technique produced
      sufficient fat suppression using only two segments (two fat suppression shots).
      Breast DCE precontrast images using DFS presented uniform fat suppression
      compared with SPIR in both axial and sagittal scans in all six volunteers.
      CONCLUSION: DFS is a promising fat suppression technique for breast imaging even
      in regions with B1 (+) inhomogeneity.

PMID- 23172832
TI  - Quantification of phenylpropanoids in commercial Echinacea products using TLC
      with video densitometry as detection technique and ANN for data modelling.
AB  - INTRODUCTION: Echinacea preparations are among the most popular herbal remedies
      worldwide. Although it is generally assigned immune enhancement activities, the
      effectiveness of Echinacea is highly dependent on the Echinacea species, part of
      the plant used, the age of the plant, its location and the method of extraction.
      OBJECTIVE: The aim of this study was to investigate the capacity of an artificial
      neural network (ANN) to analyse thin-layer chromatography (TLC) chromatograms as
      fingerprint patterns for quantitative estimation of three phenylpropanoid markers
      (chicoric acid, chlorogenic acid and echinacoside) in commercial Echinacea
      products. MATERIAL AND METHODS: By applying samples with different weight ratios
      of marker compounds to the system, a database of chromatograms was constructed.
      One hundred and one signal intensities in each of the TLC chromatograms were
      correlated to the amounts of applied echinacoside, chlorogenic acid and chicoric
      acid using an ANN. RESULTS: The developed ANN correlation was used to quantify
      the amounts of three marker compounds in Echinacea commercial formulations. The
      minimum quantifiable level of 63, 154 and 98 ng and the limit of detection of 19,
      46 and 29 ng were established for echinacoside, chlorogenic acid and chicoric
      acid respectively. CONCLUSION: A novel method for quality control of herbal
      products, based on TLC separation, high-resolution digital plate imaging and ANN
      data analysis has been developed. The method proposed can be adopted for routine
      evaluation of the phytochemical variability in Echinacea formulations available
      in the market.

PMID- 23172833
TI  - Combined application of cytology and molecular urine markers to improve the
      detection of urothelial carcinoma.
AB  - BACKGROUND: The sensitivity of cytology for the detection of urothelial carcinoma
      (UC) is limited. Newer methods such as fluorescence in situ hybridization (FISH),
      immunocytology (uCyt+), and protein markers have been developed to improve urine
      based detection of UC. As only little is known regarding the combined application
      of these markers, we investigated whether combinations of 4 of the most broadly
      available tests (cytology, FISH, uCyt+, and nuclear matrix protein 22 [NMP22
      ELISA]) may improve their diagnostic performance. METHODS: The study was
      comprised of 808 patients who were suspected of having UC. All patients underwent
      urethrocystoscopy and upper urinary tract imaging and, in the case of positive
      findings, transurethral resection/biopsy. FISH, uCyt+, cytology, and NMP22-ELISA
      were performed in all patients. RESULTS: UC was diagnosed in 115 patients
      (14.2%). Cytology and FISH were found to be the single tests with the best
      overall performance (area under the curve [AUC], 0.78/0.79). Combinations of 2,
      3, and 4 markers were found to increase the AUC to various extents compared with
      the use of single markers. Combining cytology and FISH improved the sensitivity
      and performance (AUC, 0.83) compared with the single tests and identified 12
      tumors that were not detected by cytology alone. The percentage of WHO grade
      3/carcinoma in situ tumors not detected by cytology was reduced by 62.5% when
      FISH was performed in cytology-negative patients. The addition of uCyt+ as a
      third test further improved performance (AUC, 0.86), whereas the addition of
      NMP22-ELISA was not found to have any additional influence on the performance of
      the test combination. CONCLUSIONS: The results of the current study support the
      combined use of urine markers and may form the basis of further studies
      investigating whether risk stratification based on urine marker combinations may
      individualize diagnostic algorithms and the surveillance of patients suspected of
      having UC.

PMID- 23172834
TI  - Chlorpyrifos induced testicular damage in rats: ameliorative effect of
      glutathione antioxidant.
AB  - This study investigated the induction of oxidative stress in the testes of adult
      rats exposed to chlorpyrifos (CPF). CPF was administered orally, in a dose of 30
      mg/kg body weight to male rats for 90 days, twice weekly. Coadministration of
      water-soluble nonenzymatic antioxidant glutathione (GSH) was performed in a dose
      of 100 mg/kg body weight, orally, for the same period. Another two groups of male
      rats were administered GSH and corn oil, respectively. The activities of
      superoxide dismutase and GSH reductase were decreased while the levels of lipid
      peroxidation were increased in the testicular tissues of the exposed animals.
      Testosterone level in the serum was significantly decreased. A decrease in the
      histochemical determination of testicular alkaline phosphatase was observed in
      CPF-treated rats. A significant decrease in all stages of spermatogenesis in the
      seminiferous tubules was recorded in the exposed animals. Coadministration of GSH
      restored these parameters.

PMID- 23172835
TI  - A "smart" hollandite DeNO(x) catalyst: self-protection against alkali poisoning.
AB  - Banish the villains to their own realm: biomass has gained widespread attention
      as a renewable energy source. However, commercial catalysts used in power plants
      (co-)fuelled by biomass are deactivated by the alkali-rich flue gas. In contrast,
      one of two types of active sites in a promising alkali-resistant hollandite
      catalyst traps alkali-metal ions to free up the catalytically active sites for
      the reduction of NO by NH(3).

PMID- 23172836
TI  - Pivotal role of Rho-associated kinase 2 in generating the intrinsic circadian
      rhythm of vascular contractility.
AB  - BACKGROUND: The circadian variation in the incidence of cardiovascular events may
      be attributable to the circadian changes in vascular contractility. The circadian
      rhythm of vascular contractility is determined by the interplay between the
      central and peripheral clocks. However, the molecular mechanism of the vascular
      intrinsic clock that generates the circadian rhythm of vascular contractility
      still remains largely unknown. METHODS AND RESULTS: The agonist-induced
      phosphorylation of myosin light chain in cultured smooth muscle cells
      synchronized by dexamethasone pulse treatment exhibited an apparent circadian
      oscillation, with a 25.4-hour cycle length. The pharmacological inhibition and
      knockdown of Rho-associated kinase 2 (ROCK2) abolished the circadian rhythm of
      myosin light chain phosphorylation. The expression and activity of ROCK2
      exhibited a circadian rhythm in phase with that of myosin light chain
      phosphorylation. A clock gene, RORalpha, activated the promoter of the ROCK2
      gene, whereas its knockdown abolished the rhythmic expression of ROCK2. In the
      mouse aorta, ROCK2 expression exhibited the circadian oscillation, with a peak at
      Zeitgeber time 0/24 and a nadir at Zeitgeber time 12. The myofilament Ca(2+)
      sensitization induced by GTPgammaS and U46619, a thromboxane A2 analog, at
      Zeitgeber time 0/24 was greater than that seen at Zeitgeber time 12. The
      circadian rhythm of ROCK2 expression and myofilament Ca(2+) sensitivity was
      abolished in staggerer mutant mice, which lack a functional RORalpha.
      CONCLUSIONS: ROCK2 plays a pivotal role in generating the intrinsic circadian
      rhythm of vascular contractility by receiving a cue from RORalpha. The ROCK2
      mediated intrinsic rhythm of vascular contractility may underlie the diurnal
      variation of the incidence of cardiovascular diseases.

PMID- 23172837
TI  - Between a rock and a hard place: how to align our circadian rhythms?

PMID- 23172838
TI  - Hemodynamic responses to rapid saline loading: the impact of age, sex, and heart
      failure.
AB  - BACKGROUND: Hemodynamic assessment after volume challenge has been proposed as a
      way to identify heart failure with preserved ejection fraction. However, the
      normal hemodynamic response to a volume challenge and how age and sex affect this
      relationship remain unknown. METHODS AND RESULTS: Sixty healthy subjects
      underwent right heart catheterization to measure age- and sex-related normative
      responses of pulmonary capillary wedge pressure and mean pulmonary arterial
      pressure to volume loading with rapid saline infusion (100-200 mL/min).
      Hemodynamic responses to saline infusion in heart failure with preserved ejection
      fraction (n=11) were then compared with those of healthy young (<50 years of age)
      and older (>=50 years of age) subjects. In healthy subjects, pulmonary capillary
      wedge pressure increased from 10+/-2 to 16+/-3 mm Hg after ~1 L and to 20+/-3 mm
      Hg after ~2 L of saline infusion. Older women displayed a steeper increase in
      pulmonary capillary wedge pressure relative to volume infused (16+/-4 mm Hg.L(
      1).m(2)) than the other 3 groups (P<=0.019). Saline infusion resulted in a
      greater increase in mean pulmonary arterial pressure relative to cardiac output
      in women compared with men regardless of age. Subjects with heart failure with
      preserved ejection fraction exhibited a steeper increase in pulmonary capillary
      wedge pressure relative to infused volume (25+/-12 mm Hg.L(-1).m(2)) than healthy
      young and older subjects (P<=0.005). CONCLUSIONS: Filling pressures rise
      significantly with volume loading, even in healthy volunteers. Older women and
      patients with heart failure with preserved ejection fraction exhibit the largest
      increases in pulmonary capillary wedge pressure and mean pulmonary arterial
      pressure.

PMID- 23172840
TI  - Incidence of death and potentially life-threatening near-miss events in living
      donor hepatic lobectomy: a world-wide survey.
AB  - The incidence of morbidity and mortality after living donor liver transplantation
      (LDLT) is not well understood because reporting is not standardized and relies on
      single-center reports. Aborted hepatectomies (AHs) and potentially life
      threatening near-miss events (during which a donor's life may be in danger but
      after which there are no long-term sequelae) are rarely reported. We conducted a
      worldwide survey of programs performing LDLT to determine the incidence of these
      events. A survey instrument was sent to 148 programs performing LDLT. The
      programs were asked to provide donor demographics, case volumes, and information
      about graft types, operative morbidity and mortality, near-miss events, and AHs.
      Seventy-one programs (48%), which performed donor hepatectomy 11,553 times and
      represented 21 countries, completed the survey. The average donor morbidity rate
      was 24%, with 5 donors (0.04%) requiring transplantation. The donor mortality
      rate was 0.2% (23/11,553), with the majority of deaths occurring within 60 days,
      and all but 4 deaths were related to the donation surgery. The incidences of near
      miss events and AH were 1.1% and 1.2%, respectively. Program experience did not
      affect the incidence of donor morbidity or mortality, but near-miss events and AH
      were more likely in low-volume programs (<=50 LDLT procedures). In conclusion, it
      appears that independently of program experience, there is a consistent donor
      mortality rate of 0.2% associated with LDLT donor procedures, yet increased
      experience is associated with lower rates of AH and near-miss events. Potentially
      life-threatening near-miss events and AH are underappreciated complications that
      must be discussed as part of the informed consent process with any potential
      living liver donor.

PMID- 23172839
TI  - Low serum magnesium and the development of atrial fibrillation in the community:
      the Framingham Heart Study.
AB  - BACKGROUND: Low serum magnesium has been linked to increased risk of atrial
      fibrillation (AF) after cardiac surgery. It is unknown whether hypomagnesemia
      predisposes to AF in the community. METHODS AND RESULTS: We studied 3530
      participants (mean age, 44 years; 52% women) from the Framingham Offspring Study
      who attended a routine examination and were free of AF and cardiovascular
      disease. We used Cox proportional hazard regression analysis to examine the
      association between serum magnesium at baseline and risk of incident AF. Analyses
      were adjusted for conventional AF risk factors, use of antihypertensive
      medications, and serum potassium. During up to 20 years of follow-up, 228
      participants developed AF. Mean serum magnesium was 1.88 mg/dL. The age- and sex
      adjusted incidence rate of AF was 9.4 per 1000 person-years (95% confidence
      interval, 6.7-11.9) in the lowest quartile of serum magnesium (<=1.77 mg/dL)
      compared with 6.3 per 1000 person-years (95% confidence interval, 4.1-8.4) in the
      highest quartile (>=1.99 mg/dL). In multivariable-adjusted models, individuals in
      the lowest quartile of serum magnesium were ~50% more likely to develop AF
      (adjusted hazard ratio, 1.52; 95% confidence interval, 1.00-2.31; P=0.05)
      compared with those in the upper quartiles. Results were similar after the
      exclusion of individuals on diuretics. CONCLUSIONS: Low serum magnesium is
      moderately associated with the development of AF in individuals without
      cardiovascular disease. Because hypomagnesemia is common in the general
      population, a link with AF may have potential clinical implications. Further
      studies are warranted to confirm our findings and to elucidate the underlying
      mechanisms.

PMID- 23172841
TI  - High-risk nodules detected in the hepatobiliary phase of Gd-EOB-DTPA-enhanced MR
      imaging in cirrhosis or chronic hepatitis: incidence and predictive factors for
      hypervascular transformation, preliminary results.
AB  - PURPOSE: To evaluate the incidence and predictive factors of hypervascular
      transformation during follow-up of "high-risk nodules" detected in the
      hepatobiliary phase of initial Gd-EOB-DTPA-enhanced MRI in chronic liver disease
      patients. MATERIALS AND METHODS: A total of 109 patients with chronic liver
      disease who underwent Gd-EOB-DTPA-enhanced MRI several times were investigated.
      Of these, 43 patients had 76 high-risk nodules with both hypointensity in the
      hepatobiliary phase and hypovascularity in the arterial phase of initial MRI.
      These nodules were observed until hypervascularity was detected. MRI and clinical
      findings were compared to assess the incidence and potential predictive factors
      for hypervascular transformation between the group showing hypervascular
      transformation and the group not showing hypervascularization. RESULTS: The
      median observation period was 242.5 +/- 203.2 days (range, 47-802 days). Overall,
      24 of 76 high-risk nodules (31.6%) showed hypervascular transformation during
      follow-up (median observation period, 186.0 +/- 190.3 days). The growth rate of
      the nodules (P < 0.001), the presence of fat within nodules (P = 0.037), and
      hyperintensity on T1-weighted images (P = 0.018) were significantly correlated
      with hypervascularization. CONCLUSION: Subsets of high-risk nodules tended to
      show hypervascular transformation during follow-up, with an increased growth
      rate, the presence of fat, and hyperintensity on T1-weighted images as predictive
      factors.

PMID- 23172842
TI  - Stress dissipation in the bone through various crown materials of dental implant
      restoration: a 2-D finite element analysis.
AB  - AIM: To investigate stress transmitted by various restorative materials given for
      a full veneered implant-supported crown through implants in the bone. METHODS: A
      2-D finite element model of dental implant with an abutment and full crown was
      designed. The materials used for stress dissipation were zirconia, full ceramic,
      full metal crown, composite crown, and acrylic crown. Adequate boundary
      conditions were applied, as was a vertical load of 100 N. RESULTS: The highest
      stress value was exhibited for the zirconia prosthesis model, and maximum stress
      dissipation for the same model was observed around the cervical region of the
      abutment and abutment-implant junction (24.877 Mpa). CONCLUSION: Within the
      limitations of this study, it was concluded that an occlusal material with a low
      modulus of elasticity, such as acrylic resin, dampens the occlusal impact forces,
      thereby decreasing its effect on the bone-implant interface.

PMID- 23172843
TI  - Phenolic profiling of Portuguese propolis by LC-MS spectrometry: uncommon
      propolis rich in flavonoid glycosides.
AB  - INTRODUCTION: Propolis is a chemically complex resinous substance collected by
      honeybees (Apis mellifera) from tree buds, comprising plant exudates, secreted
      substances from bee metabolism, pollen and waxes. Its chemical composition
      depends strongly on the plant sources available around the beehive, which have a
      direct impact in the quality and bioactivity of the propolis. Being as Portugal
      is a country of botanical diversity, the phenolic characterisation of propolis
      from the different regions is a priority. OBJECTIVE: Extensive characterisation
      of the phenolic composition of Portuguese propolis from different continental
      regions and islands. METHOD: Forty propolis ethanolic extracts were analysed
      extensively by liquid chromatography with diode-array detection coupled to
      electrospray ionisation tandem mass spectrometry (LC-DAD-ESI-MS(n) ). RESULTS:
      Seventy-six polyphenols were detected in the samples and two groups of propolis
      were established: the common temperate propolis, which contained the typical
      poplar phenolic compounds such as flavonoids and their methylated/esterified
      forms, phenylpropanoid acids and their esters, and an uncommon propolis type with
      an unusual composition in quercetin and kaempferol glycosides - some of them
      never described in propolis. CONCLUSION: The method allowed the establishment of
      the phenolic profile of Portuguese propolis from different geographical
      locations, and the possibility to use some phenolic compounds, such as kaempferol
      dimethylether, as geographical markers. Data suggest that other botanical species
      in addition to poplar trees can be important sources of resins for Portuguese
      propolis.

PMID- 23172844
TI  - Intraoperative transesophageal echocardiography reveals thrombotic stenosis of
      inferior vena cava during orthotopic liver transplantation.

PMID- 23172845
TI  - In vivo blood T(1) measurements at 1.5 T, 3 T, and 7 T.
AB  - The longitudinal relaxation time of blood is a crucial parameter for
      quantification of cerebral blood flow by arterial spin labeling and is one of the
      main determinants of the signal-to-noise ratio of the resulting perfusion maps.
      Whereas at low and medium magnetic field strengths (B0), its in vivo value is
      well established; at ultra-high field, this is still uncertain. In this study,
      longitudinal relaxation time of blood in the sagittal sinus was measured at 1.5
      T, 3 T, and 7 T. A nonselective inversion pulse preceding a Look-Locker echo
      planar imaging sequence was performed to obtain the inversion recovery curve of
      venous blood. The results showed that longitudinal relaxation time of blood at 7
      T was ~ 2.1 s which translates to an anticipated 33% gain in the signal-to-noise
      ratio in arterial spin labeling experiments due to T1 relaxation alone compared
      with 3 T. In addition, the linear relationship between longitudinal relaxation
      time of blood and B0 was confirmed.

PMID- 23172847
TI  - A controlled study of lifestyle treatment in primary care for children with
      obesity.
AB  - WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT: Lifestyle intervention is the most
      common treatment strategy for children with obesity. Specialized units for the
      care of children with obesity report significant effects of lifestyle treatment.
      In children, the physical activity component in lifestyle treatment is often well
      accepted. WHAT THIS STUDY ADDS: Two lifestyle treatment programmes in primary
      care for children with obesity both gave a reduction of body mass index
      significantly greater than the change observed in a non-intervention comparison
      group of children with obesity. Substituting one-third of nurse-led treatment
      sessions with sessions led by physiotherapists in one of the programmes did not
      improve the outcome. The efficacy of treatment in primary care seems to be
      comparable to that reported in the literature. OBJECTIVE: To evaluate the
      efficacy of lifestyle treatment in primary care for children with obesity.
      METHODS: In a multicentre study, sixty-four 9- to 13-year-old children with
      obesity were randomized to one of two 12-month lifestyle treatment programmes.
      The only difference between the programmes was that a physiotherapist substituted
      the nurse in one-third of the sessions in an attempt to stimulate physical
      activity. For comparison, children with normal weight and overweight, and an age
      , sex- and body mass index-matched non-intervention group of children with
      obesity were used. RESULTS: Anthropometry and laboratory data differed
      significantly between children with obesity and normal weight at baseline. The
      follow-up at the end of treatment was attended by 55 children with obesity, 28
      and 27 in each treatment arm. The mean (standard deviation) body mass standard
      deviation score changed by -0.36 (0.3) in the arm involving a physiotherapist and
      by -0.33 (0.2) in the other arm. These outcomes were not significantly different.
      Both reductions were significantly greater than the change of -0.14 (0.3)
      observed in the non-intervention comparison group of children with obesity
      CONCLUSION: The efficacy of treatment in primary care for children with obesity
      seems to be comparable to that reported in the literature. ISRCTN44919688.

PMID- 23172846
TI  - Venous and arterial flow quantification are equally accurate and precise with
      parallel imaging compressed sensing 4D phase contrast MRI.
AB  - PURPOSE: To evaluate the precision and accuracy of parallel-imaging compressed
      sensing 4D phase contrast (PICS-4DPC) magnetic resonance imaging (MRI) venous
      flow quantification in children with patients referred for cardiac MRI at our
      children's hospital. MATERIALS AND METHODS: With Institutional Review Board (IRB)
      approval and Health Insurance Portability and Accountability Act (HIPAA)
      compliance, 22 consecutive patients without shunts underwent 4DPC as part of
      clinical cardiac MRI examinations. Flow measurements were obtained in the
      superior and inferior vena cava, ascending and descending aorta, and the
      pulmonary trunk. Conservation of flow to the upper, lower, and whole body was
      used as an internal physiologic control. The arterial and venous flow rates at
      each location were compared with paired t-tests and F-tests to assess relative
      accuracy and precision. RESULTS: Arterial and venous flow measurements were
      strongly correlated with the upper (rho = 0.89), lower (rho = 0.96), and whole
      body (rho = 0.97); net aortic and pulmonary trunk flow rates were also tightly
      correlated (rho = 0.97). There was no significant difference in the value or
      precision of arterial and venous flow measurements in upper, lower, or whole
      body, although there was a trend toward improved precision with lower velocity
      encoding settings. CONCLUSION: With PICS-4DPC MRI, the accuracy and precision of
      venous flow quantification are comparable to that of arterial flow quantification
      at velocity-encodings appropriate for arterial vessels.

PMID- 23172848
TI  - Clinical outcomes in real-world patients with acute myocardial infarction
      receiving XIENCE V(r) everolimus-eluting stents: one-year results from the XIENCE
      V USA study.
AB  - OBJECTIVES: The objective of this analysis was to evaluate the safety and
      effectiveness of XIENCE V in acute myocardial infarction (AMI). BACKGROUND: The
      XIENCE V((r)) Everolimus-eluting coronary stent was superior to the TAXUS((r))
      paclitaxel-eluting stent in angiographic and clinical outcomes in the SPIRIT II,
      III, and IV randomized controlled trials, but patients with AMI were excluded.
      METHODS: XIENCE V USA is a large, prospective, multicenter, real-world single-arm
      postmarket surveillance trial. Consecutive patients undergoing PCI with XIENCE V
      were enrolled. For this analysis, clinical outcomes in 673 patients presenting
      with AMI (STEMI, n = 125) were as compared to patients without AMI (n = 3528) at
      1 year. RESULTS: At 1 year, ARC-defined stent thrombosis (ST) rates were 1.08% in
      AMI vs. 0.85% in the non-AMI group (P = 0.4987). The late ST (30 days-1 year)
      rates were 0.31% vs. 0.47% (AMI vs. non-AMI, P = 0.7551). Rates of target lesion
      revascularization (TLR) were 4.1% vs. 4.6% (P = 0.6104), and rates of target
      lesion failure (TLF) were 9.1% vs. 8.5%, (P = 0.5964). With the historical WHO
      definition of MI, 1 year TLF rates were 7.0% vs. 6.7% (P = 0.8001). Improvements
      in quality of life, angina frequency, angina stability, and physical limitations
      occurred at 6 months (each P < 0.0001) and were sustained at 1 year in both
      groups. There were no significant differences in clinical outcomes between STEMI
      and non-STEMI patients. CONCLUSIONS: At 1 year, AMI patients treated with XIENCE
      V had low rates of ST, TLR, and TLF, similar to non-AMI patients. Marked
      improvements in patients' health status in this subgroup were also demonstrated.

PMID- 23172849
TI  - Applications of helical-chiral pyridines as organocatalysts in asymmetric
      synthesis.
AB  - A new family of chiral pyridines has been designed and synthesized for use in
      asymmetric organocatalysis. Thus, helical-chiral pyridines induce high
      enantioselectivity in a range of mechanistically unrelated, synthetically
      significant transformations, including Friedel-Crafts alkylation with
      nitroalkenes, periselective Diels-Alder reactions with nitroalkenes, the ring
      opening of epoxides with a chloride nucleophile, and the propargylation of
      aldehydes.

PMID- 23172850
TI  - The genetic architecture of biofilm formation in a clinical isolate of
      Saccharomyces cerevisiae.
AB  - Biofilms are microbial communities that form on surfaces. They are the primary
      form of microbial growth in nature and can have detrimental impacts on human
      health. Some strains of the budding yeast Saccharomyces cerevisiae form colony
      biofilms, and there is substantial variation in colony architecture between
      biofilm-forming strains. To identify the genetic basis of biofilm variation, we
      developed a novel version of quantitative trait locus mapping, which leverages
      cryptic variation in a clinical isolate of S. cerevisiae. We mapped 13 loci
      linked to heterogeneity in biofilm architecture and identified the gene most
      closely associated with each locus. Of these candidate genes, six are members of
      the cyclic AMP-protein kinase A pathway, an evolutionarily conserved cell
      signaling network. Principal among these is CYR1, which encodes the enzyme that
      catalyzes production of cAMP. Through a combination of gene expression
      measurements, cell signaling assays, and gene overexpression, we determined the
      functional effects of allelic variation at CYR1. We found that increased pathway
      activity resulting from protein coding and expression variation of CYR1 enhances
      the formation of colony biofilms. Four other candidate genes encode kinases and
      transcription factors that are targets of this pathway. The protein products of
      several of these genes together regulate expression of the sixth candidate,
      FLO11, which encodes a cell adhesion protein. Our results indicate that epistatic
      interactions between alleles with both positive and negative effects on cyclic
      AMP-protein kinase A signaling underlie much of the architectural variation we
      observe in colony biofilms. They are also among the first to demonstrate genetic
      variation acting at multiple levels of an integrated signaling and regulatory
      network. Based on these results, we propose a mechanistic model that relates
      genetic variation to gene network function and phenotypic outcomes.

PMID- 23172852
TI  - The relationship between F(ST) and the frequency of the most frequent allele.
AB  - F(ST) is frequently used as a summary of genetic differentiation among groups. It
      has been suggested that F(ST) depends on the allele frequencies at a locus, as it
      exhibits a variety of peculiar properties related to genetic diversity: higher
      values for biallelic single-nucleotide polymorphisms (SNPs) than for multiallelic
      microsatellites, low values among high-diversity populations viewed as
      substantially distinct, and low values for populations that differ primarily in
      their profiles of rare alleles. A full mathematical understanding of the
      dependence of F(ST) on allele frequencies, however, has been elusive. Here, we
      examine the relationship between F(ST) and the frequency of the most frequent
      allele, demonstrating that the range of values that F(ST) can take is restricted
      considerably by the allele-frequency distribution. For a two-population model, we
      derive strict bounds on F(ST) as a function of the frequency M of the allele with
      highest mean frequency between the pair of populations. Using these bounds, we
      show that for a value of M chosen uniformly between 0 and 1 at a multiallelic
      locus whose number of alleles is left unspecified, the mean maximum F(ST) is
      ~0.3585. Further, F(ST) is restricted to values much less than 1 when M is low or
      high, and the contribution to the maximum F(ST) made by the most frequent allele
      is on average ~0.4485. Using bounds on homozygosity that we have previously
      derived as functions of M, we describe strict bounds on F(ST) in terms of the
      homozygosity of the total population, finding that the mean maximum F(ST) given
      this homozygosity is 1 - ln 2 ~ 0.3069. Our results provide a conceptual basis
      for understanding the dependence of F(ST) on allele frequencies and genetic
      diversity and for interpreting the roles of these quantities in computations of
      F(ST) from population-genetic data. Further, our analysis suggests that many
      unusual observations of F(ST), including the relatively low F(ST) values in high
      diversity human populations from Africa and the relatively low estimates of F(ST)
      for microsatellites compared to SNPs, can be understood not as biological
      phenomena associated with different groups of populations or classes of markers
      but rather as consequences of the intrinsic mathematical dependence of F(ST) on
      the properties of allele-frequency distributions.

PMID- 23172851
TI  - Dysfunctional mitochondria modulate cAMP-PKA signaling and filamentous and
      invasive growth of Saccharomyces cerevisiae.
AB  - Mitochondrial metabolism is targeted by conserved signaling pathways that mediate
      external information to the cell. However, less is known about whether
      mitochondrial dysfunction interferes with signaling and thereby modulates the
      cellular response to environmental changes. In this study, we analyzed defective
      filamentous and invasive growth of the yeast Saccharomyces cerevisiae strains
      that have a dysfunctional mitochondrial genome (rho mutants). We found that the
      morphogenetic defect of rho mutants was caused by specific downregulation of
      FLO11, the adhesin essential for invasive and filamentous growth, and did not
      result from general metabolic changes brought about by interorganellar retrograde
      signaling. Transcription of FLO11 is known to be regulated by several signaling
      pathways, including the filamentous-growth-specific MAPK and cAMP-activated
      protein kinase A (cAMP-PKA) pathways. Our analysis showed that the filamentous
      growth-specific MAPK pathway retained functionality in respiratory-deficient
      yeast cells. In contrast, the cAMP-PKA pathway was downregulated, explaining also
      various phenotypic traits observed in rho mutants. Thus, our results indicate
      that dysfunctional mitochondria modulate the output of the conserved cAMP-PKA
      signaling pathway.

PMID- 23172853
TI  - Transposing from the laboratory to the classroom to generate authentic research
      experiences for undergraduates.
AB  - Large lecture classes and standardized laboratory exercises are characteristic of
      introductory biology courses. Previous research has found that these courses do
      not adequately convey the process of scientific research and the excitement of
      discovery. Here we propose a model that provides beginning biology students with
      an inquiry-based, active learning laboratory experience. The Dynamic Genome
      course replicates a modern research laboratory focused on eukaryotic transposable
      elements where beginning undergraduates learn key genetics concepts, experimental
      design, and molecular biological skills. Here we report on two key features of
      the course, a didactic module and the capstone original research project. The
      module is a modified version of a published experiment where students experience
      how virtual transposable elements from rice (Oryza sativa) are assayed for
      function in transgenic Arabidopsis thaliana. As part of the module, students
      analyze the phenotypes and genotypes of transgenic plants to determine the
      requirements for transposition. After mastering the skills and concepts, students
      participate in an authentic research project where they use computational
      analysis and PCR to detect transposable element insertion site polymorphism in a
      panel of diverse maize strains. As a consequence of their engagement in this
      course, students report large gains in their ability to understand the nature of
      research and demonstrate that they can apply that knowledge to independent
      research projects.

PMID- 23172855
TI  - Quantitative trait loci mapping of the mouse plasma proteome (pQTL).
AB  - A current challenge in the era of genome-wide studies is to determine the
      responsible genes and mechanisms underlying newly identified loci. Screening of
      the plasma proteome by high-throughput mass spectrometry (MALDI-TOF MS) is
      considered a promising approach for identification of metabolic and disease
      processes. Therefore, plasma proteome screening might be particularly useful for
      identifying responsible genes when combined with analysis of variation in the
      genome. Here, we describe a proteomic quantitative trait locus (pQTL) study of
      plasma proteome screens in an F(2) intercross of 455 mice mapped with 177 genetic
      markers across the genome. A total of 69 of 176 peptides revealed significant LOD
      scores (>=5.35) demonstrating strong genetic regulation of distinct components of
      the plasma proteome. Analyses were confirmed by mechanistic studies and MALDI
      TOF/TOF, liquid chromatography-tandem mass spectrometry (LC-MS/MS) analyses of
      the two strongest pQTLs: A pQTL for mass-to-charge ratio (m/z) 3494 (LOD 24.9,
      D11Mit151) was identified as the N-terminal 35 amino acids of hemoglobin subunit
      A (Hba) and caused by genetic variation in Hba. Another pQTL for m/z 8713 (LOD
      36.4; D1Mit111) was caused by variation in apolipoprotein A2 (Apoa2) and
      cosegregated with HDL cholesterol. Taken together, we show that genome-wide
      plasma proteome profiling in combination with genome-wide genetic screening aids
      in the identification of causal genetic variants affecting abundance of plasma
      proteins.

PMID- 23172854
TI  - The Saccharomyces cerevisiae F-box protein Dia2 is a mediator of S-phase
      checkpoint recovery from DNA damage.
AB  - Cell-cycle progression is monitored by checkpoint pathways that pause the cell
      cycle when stress arises to threaten the integrity of the genome. Although
      activation of checkpoint pathways has been extensively studied, our understanding
      of how cells resume the cell cycle when the stress is resolved is relatively
      limited. In this study, we identify the Saccharomyces cerevisiae F-box protein
      Dia2 as a novel player in the S-phase checkpoint recovery pathway. Dia2 is
      required for robust deactivation of the Rad53 checkpoint kinase and timely
      completion of DNA replication during recovery from DNA damage induced by methyl
      methanesulfonate (MMS). Aiming to identify the substrate of SCF(Dia2)
      (Skp1/Cul1/F-box Dia2) in checkpoint recovery, we performed a genetic screen to
      identify suppressors of dia2Delta cells. The screen identified a new checkpoint
      defective allele of MRC1 truncated at the C terminus. We found that checkpoint
      defective mrc1 alleles suppress the MMS sensitivity and the checkpoint recovery
      defect of dia2Delta cells. In addition, Dia2 contributes to Mrc1 degradation
      during S-phase checkpoint recovery. Furthermore, induced degradation of
      checkpoint-functional Mrc1 partially rescues the checkpoint recovery defect of
      dia2Delta cells. We propose a model in which Dia2 mediates Mrc1 degradation to
      help cells resume the cell cycle during recovery from MMS-induced DNA damage in S
      phase.

PMID- 23172856
TI  - The relationship between long-range chromatin occupancy and polymerization of the
      Drosophila ETS family transcriptional repressor Yan.
AB  - ETS family transcription factors are evolutionarily conserved downstream
      effectors of Ras/MAPK signaling with critical roles in development and cancer. In
      Drosophila, the ETS repressor Yan regulates cell proliferation and
      differentiation in a variety of tissues; however, the mechanisms of Yan-mediated
      repression are not well understood and only a few direct target genes have been
      identified. Yan, like its human ortholog TEL1, self-associates through an N
      terminal sterile alpha-motif (SAM), leading to speculation that Yan/TEL1 polymers
      may spread along chromatin to form large repressive domains. To test this
      hypothesis, we created a monomeric form of Yan by recombineering a point mutation
      that blocks SAM-mediated self-association into the yan genomic locus and compared
      its genome-wide chromatin occupancy profile to that of endogenous wild-type Yan.
      Consistent with the spreading model predictions, wild-type Yan-bound regions span
      multiple kilobases. Extended occupancy patterns appear most prominent at genes
      encoding crucial developmental regulators and signaling molecules and are highly
      conserved between Drosophila melanogaster and D. virilis, suggesting functional
      relevance. Surprisingly, although occupancy is reduced, the Yan monomer still
      makes extensive multikilobase contacts with chromatin, with an overall pattern
      similar to that of wild-type Yan. Despite its near-normal chromatin recruitment,
      the repressive function of the Yan monomer is significantly impaired, as
      evidenced by elevated target gene expression and failure to rescue a yan null
      mutation. Together our data argue that SAM-mediated polymerization contributes to
      the functional output of the active Yan repressive complexes that assemble across
      extended stretches of chromatin, but does not directly mediate recruitment to DNA
      or chromatin spreading.

PMID- 23172857
TI  - Patterns of transcriptome divergence in the male accessory gland of two closely
      related species of field crickets.
AB  - One of the central questions in evolutionary genetics is how much of the genome
      is involved in the early stages of divergence between populations, causing them
      to be reproductively isolated. In this article, we investigate genomic
      differentiation in a pair of closely related field crickets (Gryllus firmus and
      G. pennsylvanicus). These two species are the result of allopatric divergence and
      now interact along an extensive hybrid zone in eastern North America. Genes
      encoding seminal fluid proteins (SFPs) are often divergent between species, and
      it has been hypothesized that these proteins may play a key role in the origin
      and maintenance of reproductive isolation between diverging lineages. Hence, we
      chose to scan the accessory gland transcriptome to enable direct comparisons of
      differentiation for genes known to encode SFPs with differentiation in a much
      larger set of genes expressed in the same tissue. We have characterized
      differences in allele frequency between two populations for >6000 SNPs and
      >26,000 contigs. About 10% of all SNPs showed nearly fixed differences between
      the two species. Genes encoding SFPs did not have significantly elevated numbers
      of fixed SNPs per contig, nor did they seem to show larger differences than
      expected in their average allele frequencies. The distribution of allele
      frequency differences across the transcriptome is distinctly bimodal, but the
      relatively high proportion of fixed SNPs does not necessarily imply "ancient"
      divergence between these two lineages. Further studies of linkage disequilibrium
      and introgression across the hybrid zone are needed to direct our attention to
      those genome regions that are important for reproductive isolation.

PMID- 23172859
TI  - Synthesis and evaluation of antibacterial polyurethane coatings made from soybean
      oil functionalized with dimethylphenylammonium iodide and hydroxyl groups.
AB  - Preparation of antibacterial polyurethane coatings from novel functional soybean
      oil was considered in this work. First, epoxidized soybean oil (ESBO) as a low
      price and widely available renewable resource raw material was subjected to the
      reaction with aniline using an ionic liquid as a green catalyst. The intermediate
      phenylamine containing polyol (SAP) was then methylated by reaction with methyl
      iodide to produce a polyol (QAP) with pendant dimethylphenylammonium iodide
      groups. To regulate the physical and mechanical properties as well as biological
      characteristics of final coatings, QAP was mixed with different portions of a
      similar soybean oil-based polyol (MSP) without quaternary ammonium groups. The
      mixtures were reacted with isophorone diisocyanate to produce crosslinked
      polyurethane coatings. Evaluation of viscoelastic properties by DMA method
      revealed single phase structure with Tg in the range of 50-82 degrees C. Stress
      strain analysis of the prepared polyurethanes showed initial modulus, tensile
      strength, and elongation at break in the ranges of 13-299 MPa, 4.5-13.8 MPa, and
      16-109%, respectively. Additionally, the coatings showed good adherence to
      aluminum and PVC substrates. The solvent extracted samples showed excellent
      biocompatibility as determined by monitoring L929 fibroblast cells morphology and
      MTT assay. Meanwhile, very promising antibacterial properties against both Gram
      positive (S. aureus) and Gram-negative (E. coli) bacteria with bacterial
      reduction in the range of 83-100% was observed.

PMID- 23172858
TI  - Waist circumference measurement site does not affect relationships with visceral
      adiposity and cardiometabolic risk factors in children.
AB  - WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT: A number of anatomic sites are used for
      the measurement of waist circumference. A number of studies have documented
      differences in the absolute values of waist circumference measurements across
      these common sites in adults. It is unclear whether waist circumference
      measurement site alters the relationship with abdominal adiposity and
      cardiometabolic risk factors in children. WHAT THIS STUDY ADDS: The absolute
      values of waist circumference at four anatomic locations (minimal, midway, iliac,
      umbilicus) differed and this affected prevalence of high (>=90th percentile)
      waist circumference. The relationships between waist circumference values at four
      anatomic locations and both depot-specific adiposity and cardiometabolic risk
      factors were similar across race and sex groups. BACKGROUND: Different waist
      circumference (WC) measurement sites are used in clinical and epidemiological
      settings. OBJECTIVES: To examine differences in WC measurement at four anatomic
      sites and how each WC measurement relates to visceral adipose tissue (VAT) and
      cardiometabolic risk factors in children. METHODS: A total of 371 white and
      African-American children aged 5 to 18 years had WC measured at four sites:
      minimal waist, midpoint between the iliac crest and the lowest rib, superior
      border of the iliac crest and the umbilicus. Abdominal VAT was measured using
      magnetic resonance imaging and cardiometabolic risk factors were defined using
      National Heart, Lung and Blood Institute guidelines. Relationships between WC
      sites and VAT and risk factors were explored in each race-by-sex group. RESULTS:
      All WC sites were highly correlated (r = 0.97 to 0.99). Differences in absolute
      mean WC values existed in all race-by-sex groups, and this affected the
      prevalence of high WC (>=90th percentile). Values were lowest for minimal waist
      and highest for umbilicus. Age-controlled partial correlations between WC and
      logVAT VAT were 0.81-0.89 (all P < 0.001) and between WC and cardiometabolic risk
      factors were -0.24 to -0.41 and 0.19 to 0.52 (all P < 0.05). CONCLUSIONS:   While
      the absolute values of WC at four anatomic locations differed, the relationships
      between WC values and both VAT and cardiometabolic risk factors were similar
      within all race-by-sex groups.

PMID- 23172860
TI  - Intron-centric estimation of alternative splicing from RNA-seq data.
AB  - MOTIVATION: Novel technologies brought in unprecedented amounts of high
      throughput sequencing data along with great challenges in their analysis and
      interpretation. The percent-spliced-in (PSI, ) metric estimates the incidence of
      single-exon-skipping events and can be computed directly by counting reads that
      align to known or predicted splice junctions. However, the majority of human
      splicing events are more complex than single-exon skipping. RESULTS: In this
      short report, we present a framework that generalizes the metric to arbitrary
      classes of splicing events. We change the view from exon centric to intron
      centric and split the value of into two indices, and , measuring the rate of
      splicing at the 5' and 3' end of the intron, respectively. The advantage of
      having two separate indices is that they deconvolute two distinct elementary acts
      of the splicing reaction. The completeness of splicing index is decomposed in a
      similar way. This framework is implemented as bam2ssj, a BAM-file-processing
      pipeline for strand-specific counting of reads that align to splice junctions or
      overlap with splice sites. It can be used as a consistent protocol for
      quantifying splice junctions from RNA-seq data because no such standard procedure
      currently exists. AVAILABILITY: The C code of bam2ssj is open source and is
      available at https://github.com/pervouchine/bam2ssj CONTACT: dp@crg.eu

PMID- 23172861
TI  - DOOSS: a tool for visual analysis of data overlaid on secondary structures.
AB  - MOTIVATION: DOOSS (Data Overlaid On Secondary Structures) is a tool for
      visualizing annotated secondary structures of large single-stranded nucleotide
      sequences (such as full-length virus genomes). The purpose of this tool is to
      assist investigators in evaluating the biological relevance of secondary
      structures within particular sequences. AVAILABILITY AND IMPLEMENTATION: DOOSS is
      written in Java and is available from: http://dooss.computingforbiology.org
      CONTACT: michaelgolden0@gmail.com SUPPLEMENTARY INFORMATION: Supplementary data
      are available at Bioinformatics online.

PMID- 23172862
TI  - Non-redundant compendium of human ncRNA genes in GeneCards.
AB  - MOTIVATION: Non-coding RNA (ncRNA) genes are increasingly acknowledged for their
      importance in the human genome. However, there is no comprehensive non-redundant
      database for all such human genes. RESULTS: We leveraged the effective platform
      of GeneCards, the human gene compendium, together with the power of fRNAdb and
      additional primary sources, to judiciously unify all ncRNA gene entries
      obtainable from 15 different primary sources. Overlapping entries were clustered
      to unified locations based on an algorithm employing genomic coordinates. This
      allowed GeneCards' gamut of relevant entries to rise ~5-fold, resulting in
      ~80,000 human non-redundant ncRNAs, belonging to 14 classes. Such 'grand
      unification' within a regularly updated data structure will assist future ncRNA
      research. AVAILABILITY AND IMPLEMENTATION: All of these non-coding RNAs are
      included among the ~122,500 entries in GeneCards V3.09, along with pertinent
      annotation, automatically mined by its built-in pipeline from 100 data sources.
      This information is available at www.genecards.org. CONTACT:
      Frida.Belinky@weizmann.ac.il SUPPLEMENTARY INFORMATION: Supplementary data are
      available at Bioinformatics online.

PMID- 23172863
TI  - An empirical Bayes approach for analysis of diverse periodic trends in time
      course gene expression data.
AB  - MOTIVATION: There is a substantial body of works in the biology literature that
      seeks to characterize the cyclic behavior of genes during cell division. Gene
      expression microarrays made it possible to measure the expression profiles of
      thousands of genes simultaneously in time-course experiments to assess changes in
      the expression levels of genes over time. In this context, the commonly used
      procedures for testing include the permutation test by de Lichtenberg et al. and
      the Fisher's G-test, both of which are designed to evaluate periodicity against
      noise. However, it is possible that a gene of interest may have expression that
      is neither cyclic nor just noise. Thus, there is a need for a new test for
      periodicity that can identify cyclic patterns against not only noise but also
      other non-cyclic patterns such as linear, quadratic or higher order polynomial
      patterns. RESULTS: To address this weakness, we have introduced an empirical
      Bayes approach to test for periodicity and compare its performance in terms of
      sensitivity and specificity with that of the permutation test and Fisher's G-test
      through extensive simulations and by application to a set of time-course
      experiments on the Schizosaccharomyces pombe cell-cycle gene expression. We use
      'conserved' and 'cycling' genes by Lu et al. to assess the sensitivity and CESR
      genes by Chenet al. to assess the specificity of our new empirical Bayes method.
      AVAILABILITY AND IMPLEMENTATION: The SAS Macro for our empirical Bayes test for
      periodicity is included in the supplementary materials along with a sample run of
      the MACRO program. CONTACT: mkocak1@uthsc.edu SUPPLEMENTARY INFORMATION:
      Supplementary data are available at Bioinformatics online.

PMID- 23172864
TI  - Scribl: an HTML5 Canvas-based graphics library for visualizing genomic data over
      the web.
AB  - MOTIVATION: High-throughput biological research requires simultaneous
      visualization as well as analysis of genomic data, e.g. read alignments, variant
      calls and genomic annotations. Traditionally, such integrative analysis required
      desktop applications operating on locally stored data. Many current terabyte-size
      datasets generated by large public consortia projects, however, are already only
      feasibly stored at specialist genome analysis centers. As even small laboratories
      can afford very large datasets, local storage and analysis are becoming
      increasingly limiting, and it is likely that most such datasets will soon be
      stored remotely, e.g. in the cloud. These developments will require web-based
      tools that enable users to access, analyze and view vast remotely stored data
      with a level of sophistication and interactivity that approximates desktop
      applications. As rapidly dropping cost enables researchers to collect data
      intended to answer questions in very specialized contexts, developers must also
      provide software libraries that empower users to implement customized data
      analyses and data views for their particular application. Such specialized, yet
      lightweight, applications would empower scientists to better answer specific
      biological questions than possible with general-purpose genome browsers currently
      available. RESULTS: Using recent advances in core web technologies (HTML5), we
      developed Scribl, a flexible genomic visualization library specifically targeting
      coordinate-based data such as genomic features, DNA sequence and genetic
      variants. Scribl simplifies the development of sophisticated web-based graphical
      tools that approach the dynamism and interactivity of desktop applications.
      AVAILABILITY AND IMPLEMENTATION: Software is freely available online at
      http://chmille4.github.com/Scribl/ and is implemented in JavaScript with all
      modern browsers supported.

PMID- 23172865
TI  - High-throughput microbial population genomics using the Cortex variation
      assembler.
AB  - SUMMARY: We have developed a software package, Cortex, designed for the analysis
      of genetic variation by de novo assembly of multiple samples. This allows direct
      comparison of samples without using a reference genome as intermediate and
      incorporates discovery and genotyping of single-nucleotide polymorphisms, indels
      and larger events in a single framework. We introduce pipelines which simplify
      the analysis of microbial samples and increase discovery power; these also enable
      the construction of a graph of known sequence and variation in a species, against
      which new samples can be compared rapidly. We demonstrate the ease-of-use and
      power by reproducing the results of studies using both long and short reads.
      AVAILABILITY: http://cortexassembler.sourceforge.net (GPLv3 license). CONTACT:
      zam@well.ox.ac.uk, mcvean@well.ox.ac.uk SUPPLEMENTARY INFORMATION: Supplementary
      data are available at Bioinformatics online.

PMID- 23172866
TI  - Nystagmus in SCA territory cerebellar infarction: pattern and a possible
      mechanism.
AB  - OBJECTIVES: To investigate the frequency and pattern of nystagmus associated with
      isolated cerebellar infarction in the territory of the superior cerebellar artery
      (SCA) and to discuss its possible mechanism. METHODS: We identified 41
      consecutive patients with isolated SCA territory cerebellar infarction diagnosed
      by MRI. Each patient completed a standardised dizziness questionnaire and
      underwent neurotological evaluations. Eye movements were recorded using 3
      dimensional video-oculography during the acute period. RESULTS: Approximately
      half (19/41) of the patients experienced true vertigo early in the course of the
      SCA distribution infarct. 11 (27%) of the 41 patients showed spontaneous
      nystagmus (SN) or direction changed bidirectional gaze-evoked nystagmus (GEN). SN
      was observed in 10 patients (24%) and the horizontal component of SN was
      predominant in most case (80%, 8/10) and always beat towards the lesion side.
      Direction changed bidirectional GEN was observed in five patients and was mostly
      (4/5) accompanied by SN. Lesion subtraction analyses revealed that damage to the
      rostral anterior cerebellum including the ala of the central lobule and part of
      the quadrangular lobule was more frequent in patients with nystagmus compared to
      patients without nystagmus (9/11, 82% vs 11/30, 37%) (p=0.015). In most (82%,
      9/11) patients with SN or GEN, the nystagmus subsided within 1 week after
      hospitalisation. DISCUSSION: Vertigo and nystagmus in SCA territory cerebellar
      infarction are more common than previously thought. Ipsilesional SN may result
      from damage to the anterior lobe of the cerebellum, which transmits the
      vestibular output to the fastigial nucleus.

PMID- 23172867
TI  - Feasibility, safety and cost of outpatient management of acute minor ischaemic
      stroke: a population-based study.
AB  - BACKGROUND: Outpatient management safely and effectively prevents early recurrent
      stroke after transient ischaemic attack (TIA), but this approach may not be safe
      in patients with acute minor stroke. OBJECTIVE: To study outcomes of clinic and
      hospital-referred patients with TIA or minor stroke (National Institute of Health
      Stroke Scale score <=3) in a prospective, population-based study (Oxford Vascular
      Study). RESULTS: Of 845 patients with TIA/stroke, 587 (69%) were referred
      directly to outpatient clinics and 258 (31%) directly to inpatient services. Of
      the 250 clinic-referred minor strokes (mean age 72.7 years), 237 (95%) were
      investigated, treated and discharged on the same day, of whom 16 (6.8%) were
      subsequently admitted to hospital within 30 days for recurrent stroke (n=6),
      sepsis (n=3), falls (n=3), bleeding (n=2), angina (n=1) and nursing care (n=1).
      The 150 patients (mean age 74.8 years) with minor stroke referred directly to
      hospital (median length-of-stay 9 days) had a similar 30-day readmission rate
      (9/150; 6.3%; p=0.83) after initial discharge and a similar 30-day risk of
      recurrent stroke (9/237 in clinic patients vs 8/150, OR=0.70, 0.27-1.80, p=0.61).
      Rates of prescription of secondary prevention medication after initial
      clinic/hospital discharge were higher in clinic-referred than in hospital
      referred patients for antiplatelets/anticoagulants (p<0.05) and lipid-lowering
      agents (p<0.001) and were maintained at 1-year follow-up. The mean (SD) secondary
      care cost was L8323 (13 133) for hospital-referred minor stroke versus L743
      (1794) for clinic-referred cases. CONCLUSION: Outpatient management of clinic
      referred minor stroke is feasible and may be as safe as inpatient care. Rates of
      early hospital admission and recurrent stroke were low and uptake and maintenance
      of secondary prevention was high.

PMID- 23172869
TI  - When patient opinion and clinical science are implacably opposed: the view from
      an MS specialist.

PMID- 23172868
TI  - Risk for late-life re-injury, dementia and death among individuals with traumatic
      brain injury: a population-based study.
AB  - OBJECTIVES: To determine the association of self-reported traumatic brain injury
      (TBI) with loss of consciousness (LOC) with late-life re-injury, dementia
      diagnosis and mortality. DESIGN: Ongoing longitudinal population-based
      prospective cohort study. SETTING: Seattle-area integrated health system.
      PARTICIPANTS: 4225 dementia-free individuals age 65 and older were randomly
      selected and enrolled between 1994 and 2010. Participants were seen every 2
      years, with mean (range) follow-up of 7.4 (0-16) years. 606 (14%) participants
      reported a lifetime history of TBI with LOC at enrolment. 3466 participants
      provided information regarding lifetime history of TBI and completed at least one
      follow-up visit. MAIN OUTCOME MEASURES: Self-reported TBI with LOC after study
      entry, incident all-cause dementia and Alzheimer's disease (AD), and all-cause
      mortality. RESULTS: There were 25 567 person-years of follow-up. History of TBI
      with LOC reported at study enrolment was associated with increased risk for TBI
      with LOC during follow-up, with adjusted HRs ranging from 2.54 (95% CI 1.42 to
      4.52) for those reporting first injury before age 25 to 3.79 (95% CI 1.89 to
      7.61) for those with first injury after age 55. History of TBI with LOC was not
      associated with elevated risk for developing dementia or AD. There was no
      association between baseline history of TBI with LOC and mortality, though TBI
      with LOC since the previous study visit ('recent TBI') was associated with
      increased mortality (HR 2.12, 95% CI 1.62 to 2.78). CONCLUSIONS: Individuals aged
      65 or older who reported a history of TBI with LOC at any time in their lives
      were at elevated risk of subsequent re-injury. Recent TBI with LOC sustained in
      older adulthood was associated with increased risk for mortality. Findings
      support the need for close clinical monitoring of older adults who sustain a TBI
      with LOC.

PMID- 23172870
TI  - No gain - no pain?

PMID- 23172871
TI  - Hyperhomocysteinemia and methylenetetrahydrofolate reductase C677T polymorphism
      in cerebral veno-sinus thrombosis.
AB  - There is limited data on the role of hyperhomocysteinemia as a risk factor for
      cerebral veno-sinus thrombosis (CVT) in Indians. We examined the association
      between plasma homocysteine (Hcy), methylenetetrahydrofolate reductase (MTHFR)
      C677T polymorphism, and CVT in 185 patients with aseptic CVT (puerperal 80 and
      nonpuerperal 105) and 248 healthy controls (puerperal 67 and nonpuerperal 181).
      Fasting Hcy was higher in patients compared to controls (20.25 +/- 5.97 vs 9.81
      +/- 5.19 MUmol/L, P < .001) and associated with 4.54-fold (95% confidence
      interval [CI]: 2.74-7.53) increase in risk of CVT. Risk was higher in puerperal
      (odds ratio [OR]: 8.7, 95% CI: 2.73-26.91) compared to nonpuerperal CVT (OR:
      3.82, 95% CI: 2.09-6.96). Plasma Hcy was higher in MTHFR 677TT compared to 677CT
      and 677CC genotypes (34.44 +/- 32.8 vs 25.81 +/- 33.3 vs 18.50 +/- 23.7 MUmol/L,
      respectively, P < .001), but the risk associated with MTHFR 677TT was
      insignificant (OR: 1.91, 95% CI: 0.53-7.06). We conclude that
      hyperhomocysteinemia is a risk marker for Indian patients with aseptic CVT. MTHFR
      677TT genotype is not linked with CVT but is a determinant of plasma Hcy. 

PMID- 23172872
TI  - GATA3 acts upstream of FOXA1 in mediating ESR1 binding by shaping enhancer
      accessibility.
AB  - Estrogen receptor (ESR1) drives growth in the majority of human breast cancers by
      binding to regulatory elements and inducing transcription events that promote
      tumor growth. Differences in enhancer occupancy by ESR1 contribute to the diverse
      expression profiles and clinical outcome observed in breast cancer patients.
      GATA3 is an ESR1-cooperating transcription factor mutated in breast tumors;
      however, its genomic properties are not fully defined. In order to investigate
      the composition of enhancers involved in estrogen-induced transcription and the
      potential role of GATA3, we performed extensive ChIP-sequencing in unstimulated
      breast cancer cells and following estrogen treatment. We find that GATA3 is
      pivotal in mediating enhancer accessibility at regulatory regions involved in
      ESR1-mediated transcription. GATA3 silencing resulted in a global redistribution
      of cofactors and active histone marks prior to estrogen stimulation. These global
      genomic changes altered the ESR1-binding profile that subsequently occurred
      following estrogen, with events exhibiting both loss and gain in binding
      affinity, implying a GATA3-mediated redistribution of ESR1 binding. The GATA3
      mediated redistributed ESR1 profile correlated with changes in gene expression,
      suggestive of its functionality. Chromatin loops at the TFF locus involving ESR1
      bound enhancers occurred independently of ESR1 when GATA3 was silenced,
      indicating that GATA3, when present on the chromatin, may serve as a licensing
      factor for estrogen-ESR1-mediated interactions between cis-regulatory elements.
      Together, these experiments suggest that GATA3 directly impacts ESR1 enhancer
      accessibility, and may potentially explain the contribution of mutant-GATA3 in
      the heterogeneity of ESR1+ breast cancer.

PMID- 23172873
TI  - 'A tale of two cases:' the health, illness, and physical activity stories of two
      children living with cystic fibrosis.
AB  - Storytelling is perennial, and central to the human condition. Although illness
      may shatter identity and one's role and place in the broader social world,
      narrative may aid in the process of self-reparation. Despite the merits of the
      narrative approach, it has been underutilized with children who are living with
      cystic fibrosis (CF). The role that illness narratives may play in influencing CF
      youths' physical activity also remains poorly investigated. This article drew on
      the qualitative case study methodological tradition to narrate the stories of two
      children living with CF at a children's hospital in Canada. The findings beg
      researchers to consider (a) how children with life-limiting diseases borrow
      multiple illness narrative types, (b) the role of development in influencing the
      kinds of stories that children can tell, and (c) the impact of illness narratives
      on physical activity. By rendering the tales of two CF youth in this study, we
      respond to Aurthur Frank's call; taking a multiple narrative turn, we listen to
      stories of a different kind of suffering. 

PMID- 23172874
TI  - Stigmatization predicts psychological adjustment and quality of life in children
      and adolescents with a facial difference.
AB  - OBJECTIVES: This cross-sectional study assessed psychological adjustment and
      health-related quality of life (HRQOL) in children and adolescents with
      congenital or acquired facial differences and identified potential predictors of
      adjustment. METHODS: Data were obtained from 88 children, ages 9 months to 16
      years, by means of parent questionnaires (n = 86) and standardized interviews
      with children >=7 years old (n = 31). Evaluation measures included the Child
      Behavior Checklist (CBCL), KIDSCREEN-27, TNO-AZL Preschool Quality of Life
      Questionnaire (TAPQOL), and Perceived Stigmatization Questionnaire. RESULTS:
      Psychological adjustment, as measured by the CBCL, was within norms. Parent
      reported HRQOL was good in preschool children. Parent- and self-reported HRQOL of
      participants 7-16 years old was impaired in several dimensions, including
      psychological well-being. Psychological adjustment (especially internalizing
      behavior problems) and HRQOL were predicted primarily by perceived
      stigmatization. CONCLUSIONS: Identification of stigma experiences and appropriate
      support may be crucial to enhancing psychological adjustment and quality of life
      in children with facial disfigurement.

PMID- 23172875
TI  - An efficient method for selectively imaging and quantifying in situ the
      expression of sialylated glycoproteins on living cells.
AB  - A simple and efficient method for selectively imaging and monitoring in situ the
      expression of sialylated glycoproteins on living cells has been developed.
      Treating living cells by mild periodate oxidation to selectively generate
      aldehydes on sialylated glycoproteins, followed by direct labeling of aldehydes
      with a commercially available fluorescent tag, fluorescein-5-thiosemicarbazide
      (FTSC), allows in situ imaging and quantification of sialylated glycoproteins on
      living cells. Under optimum reaction conditions, the periodate oxidation-based
      FTSC ligation (PF) strategy could be completed within 40 min. The cells
      undergoing the PF assay revealed a 91% viability and a fairly high-level of
      metabolic activity. Compared with current labeling methods, the PF assay proved
      to be a simpler and faster means of imaging sialylated glycoproteins on living
      cells. The PF assay has been successfully applied to imaging the location and
      quantification of the abundance of sialylated glycoproteins on tumor and normal
      cells. Our results demonstrated the methodological significance in clinical
      diagnosis and functional elucidation studies.

PMID- 23172876
TI  - Are anti-LGBT homicides in the United States unique?
AB  - An integral issue to the study of bias crimes is how violence targeting lesbian,
      gay, bisexual, and transgender (LGBT) victims is different from other more common
      forms of violent crimes. Limitations in official bias crimes data have inhibited
      our understanding of the relative nature of anti-LGBT crimes. The purpose of this
      study is to examine the similarities and differences in anti-LGBT homicides and
      average homicides in the United States between 1990 and 2008. The current study
      addresses methodological issues by relying on an open-source database of anti
      LGBT homicides. This study found that the nature of these homicides is both
      similar and significantly different from the average homicide. Implications for
      the ongoing bias crimes discourse are discussed.

PMID- 23172877
TI  - Photoreceptor impairment on optical coherence tomographic images in patients with
      retinitis pigmentosa.

PMID- 23172878
TI  - Post-chemoreduction cryptic optic nerve relapse in a patient with bilateral
      retinoblastoma.

PMID- 23172879
TI  - Association between external limiting membrane status and visual acuity in
      diabetic macular oedema.
AB  - AIM: To evaluate the association between the foveal external limiting membrane
      (ELM) status and visual acuity (VA) in diabetic macular oedema (DMO). METHODS: We
      retrospectively reviewed the spectral domain optical coherence tomography images
      of 127 eyes from 127 patients with DMO and evaluated the correlation between the
      logarithm of the minimal angle of resolution (logMAR) VA and the statuses of the
      foveal ELM, inner segment/outer segment (IS/OS) and cone outer segment tips
      (COST); foveal macular thickness (FMT); and presence or absence of hard exudates
      (HE), serous retinal detachment (SRD) and vitreous adhesion. The integrity of the
      ELM, IS/OS, and COST was classified into three categories (absent, disrupted and
      complete). RESULTS: There was a strong correlation between VA and the statuses of
      the ELM (r=0.699, p<0.001), IS/OS (r=0.716, p<0.001) and COST (r=0.471, p<0.001).
      There was no correlation between FMT and logMAR VA (r=-0.036, p=0.687). However,
      when we analysed the correlation between FMT and VA by dividing patients into
      those with FMT <=250 MUm and those with FMT >250 MUm, there was a positive
      correlation between FMT and VA in eyes with FMT <=250 MUm (r=-0.601, p<0.0001)
      and a negative correlation in eyes with FMT>250 MUm (r=0.290, p<0.01). Other
      factors HE, SRD and vitreous adhesion did not correlate with VA. CONCLUSIONS: In
      DMO, the ELM status may be as closely related to VA as the IS/OS status.

PMID- 23172880
TI  - Expression of an anti-CD4 single-chain antibody fragment from the donor cornea
      can prolong corneal allograft survival in inbred rats.
AB  - AIM: To investigate whether expression of an anti-CD4 antibody fragment (scFv) by
      a lentivector-transduced donor cornea can prolong rat corneal allograft survival.
      METHODS: Inbred Fischer 344 rats received penetrating corneal allografts from
      Wistar-Furth donors after a 3 h transduction of the donor cornea with a
      lentivector carrying anti-CD4scFv cDNA (Lv-CD4scFv), a lentivector carrying the
      reporter gene-enhanced yellow fluorescence protein (LV-eYFP), or an adenoviral
      vector carrying anti-CD4 scFv cDNA (Ad-CD4scFv). Unmodified controls were also
      performed. Graft survival was assessed by corneal clarity, and rejection was
      confirmed histologically. RESULTS: In organ-cultured corneas, expression of anti
      CD4 scFv was detected at 2 days post-transduction with the adenoviral vector,
      compared with 5 days post-transduction with the lentivector, and was 10-fold
      higher than the former. More inflammation was observed in Ad-CD4scFv-modified
      allografts than in Lv-CD4scFv-modified grafts at 15 days postsurgery (p=0.01).
      The median time to rejection for unmodified, LV-eYFP and Ad-CD4scFv grafts was
      day 17, compared with day 22 for Lv-CD4scFv grafts (p<=0.018). CONCLUSION: Donor
      corneas transduced with a lentiviral vector carrying anti-CD4scFv cDNA showed a
      modest but significant prolongation in graft survival compared with unmodified,
      Lv-eYFP and Ad-CD4scFv grafts. However, rejection still occurred in all Lv
      CD4scFv grafts, indicating that sensitisation may have been delayed but was not
      prevented.

PMID- 23172881
TI  - Diphtheria toxin-epidermal growth factor fusion protein DAB389EGF for the
      treatment of bladder cancer.
AB  - PURPOSE: The novel fusion protein, DAB(389)EGF, is composed of both the catalytic
      and the translocation domains of diphtheria toxin that are fused to the human
      EGF, providing a targeting and a toxicity component. We tested DAB(389)EGF for
      antitumor activity in both in vitro and in vivo urinary bladder cancer models.
      EXPERIMENTAL DESIGN: Human bladder cancer lines were treated with DAB(389)EGF and
      assessed for growth inhibition and clonogenic suppression. Using 6- to 8-week-old
      female athymic nude mice implanted orthotopically with HTB9 cells, DAB(389)EGF
      was administered intravesically twice weekly for 2 weeks. The response of the
      luciferase-expressing HTB9 cells was monitored via bioluminescence as the primary
      endpoint. RESULTS: Treatment response with DAB(389)EGF was specific and robust,
      with an IC(50) ranging from 0.5 to 15 ng/mL in eight tested bladder cancer cell
      lines, but greater than 50 ng/mL in the EGF receptor (EGFR)-negative H520 control
      cell line. Simulating short-duration intravesical therapy used clinically, a 2
      hour treatment exposure of DAB(389)EGF (10 ng/mL) produced clonogenic suppression
      in three selected bladder cancer cell lines. In vivo, luciferase activity was
      suppressed in five of six mice treated with DAB(389)EGF [70 MUL (1 ng/MUL) per
      mouse], as compared with only one of six mice treated with a control diphtheria
      toxin (DT) fusion protein. Histologic assessment of tumor clearance correlated
      with the bioluminescent changes observed with DAB(389)EGF treatment.
      Immunocompetent mice treated with intravesical DAB(389)EGF did not show any
      nonspecific systemic toxicity. CONCLUSIONS: The intravesical delivery of targeted
      toxin fusion proteins is a novel treatment approach for non-muscle-invasive
      urinary bladder cancer. With appropriate targeting, the treatments are effective
      and well-tolerated in vivo.

PMID- 23172882
TI  - Competing risks and multistate models.
AB  - Complex clinical endpoints are present in studies in cancer. Especially in
      studies on hematopoietic stem-cell transplantation (HSCT), various risks exist
      after HSCT. Patients can experience acute and chronic graft versus host disease
      (GVHD) or need to undergo immunosuppressive therapy (IST), a relapse can occur,
      or patients can die after relapse or without former relapse (nonrelapse
      mortality, NRM). Sometimes, endpoints can be reasonably combined in a composite
      endpoint, as, for example, relapse and NRM are combined into disease-free
      survival (DFS). In this case, standard survival techniques, as Kaplan-Meier
      estimation of the DFS probability, can be applied. Often, interest focuses on
      endpoints for which competing risks are present, as, for example, GVHD, with
      death without prior GVHD as competing risk. This results in a competing risks
      model, a special case of a multistate model. A more complex multistate model is
      required when the effects of events occurring in the course of the study on
      further disease process shall be investigated, as, for example, the effect of
      GVHD on relapse and NRM. Another endpoint of interest is time under IST. As
      patients usually experience multiple episodes of IST, thus switching back and
      forth between "IST" and "no IST" during follow-up, the multistate model used for
      analysis must be adapted for this event structure. The aim of this nontechnical
      report is to explain use and interpretation of Cox-type regression models
      suitable for the different situations in a randomized trial on the effects of
      anti-T-cell globulin as GVHD prophylaxis.

PMID- 23172883
TI  - Secrets of drug resistance in NSCLC exposed by new molecular definition of EMT.
AB  - Non-small cell lung carcinoma (NSCLC) metastasis and drug resistance has been
      associated with epithelial-to-mesenchymal transition (EMT). This study reports
      the development of a robust gene expression signature of EMT in NSCLC and reveals
      new insights into the key molecular events that underlie EMT and drug resistance
      in NSCLC.

PMID- 23172884
TI  - Variation in precursor lesions of pancreatic cancer among high-risk groups.
AB  - PURPOSE: Pancreatic ductal adenocarcinoma (PDAC) surveillance programs are
      currently offered to high-risk individuals aiming to detect precursor lesions or
      PDAC at an early stage. We assessed differences in frequency and behavior of
      precursor lesions and PDAC between two high-risk groups. EXPERIMENTAL DESIGN:
      Individuals with a p16-Leiden germline mutation (N = 116; median age 54 years)
      and individuals from familial pancreatic cancer (FPC) families (N = 125; median
      age 47 years) were offered annual surveillance by MRI and magnetic resonance
      cholangiopancreatography (MRCP) with or without endoscopic ultrasound (EUS) for a
      median surveillance period of 34 months (0-127 months) or 36 months (0-110
      months), respectively. Detailed information was collected on pancreatic cystic
      lesions detected on MRCP and precursor lesions in surgical specimens of patients
      who underwent pancreatic surgery. RESULTS: Cystic lesions were more common in the
      FPC cohort (42% vs. 16% in p16-Leiden cohort), whereas PDAC was more common in
      the p16-Leiden cohort (7% vs. 0.8% in FPC cohort). Intraductal papillary mucinous
      neoplasm (IPMN) was a common finding in surgical specimens of FPC-individuals,
      and was only found in two patients of the p16-Leiden cohort. In the p16-Leiden
      cohort, a substantial proportion of cystic lesions showed growth or malignant
      transformation during follow-up, whereas in FPC individuals most cystic lesions
      remain stable. CONCLUSION: In p16-Leiden mutation carriers, cystic lesions have a
      higher malignant potential than in FPC-individuals. On the basis of these
      findings, a more intensive surveillance program may be considered in this high
      risk group.

PMID- 23172885
TI  - Tumor burden modeling versus progression-free survival for phase II decision
      making.
AB  - Randomized Phase II oncology trial endpoints for decision making include both
      progression-free survival (PFS) and change in tumor burden as measured by the sum
      of longest diameters (SLD) of the target lesions. In addition to observed SLD
      changes, tumor shrinkage and growth parameters can be estimated from the patient
      specific SLD profile over time. The ability of these SLD analyses to identify an
      active drug is contrasted with that of a PFS analysis through the simulation of
      Phase II trials via resampling from each of 6 large, Phase II and III trials, 5
      of which were positive and one negative. From each simulated Phase II trial, a P
      value was obtained from 4 analyses-a log-rank test on PFS, a Wilcoxon rank-sum
      test on the minimum observed percentage change from baseline in SLD, and 2
      nonlinear, mixed-effects model analyses of the SLD profiles. All 4 analyses led
      to approximately uniformly distributed P values in the negative trial. The PFS
      analysis was the best or nearly the best analysis in the other 5 trials. In only
      one of the positive studies did the modeling analysis outperform the analysis of
      the minimum SLD. In conclusion, for the decision to start a Phase III trial based
      on the results of a randomized Phase II trial of an oncology drug, PFS appears to
      be a better endpoint than does SLD, whether analyzed through simple SLD
      endpoints, such as the minimum percentage change from baseline, or through the
      modeling of the SLD time course to estimate tumor dynamics.

PMID- 23172886
TI  - Breast cancer treatment with imiquimod: applying an old lotion to a new disease.
AB  - Over the prior two decades, imiquimod, a toll-like receptor 7 agonist, has been
      applied to nearly 50 clinical settings. Because of its immunomodulatory role, the
      topical cream today, for the first time, is being applied to cutaneous breast
      cancer in preclinical models and in a phase II clinical trial.

PMID- 23172887
TI  - Targeting the phosphoinositide 3-kinase p110-alpha isoform impairs cell
      proliferation, survival, and tumor growth in small cell lung cancer.
AB  - PURPOSE: The phosphoinositide 3-kinase (PI3K) pathway is fundamental for cell
      proliferation and survival and is frequently altered and activated in neoplasia,
      including carcinomas of the lung. In this study, we investigated the potential of
      targeting the catalytic class I(A) PI3K isoforms in small cell lung cancer
      (SCLC), which is the most aggressive of all lung cancer types. EXPERIMENTAL
      DESIGN: The expression of PI3K isoforms in patient specimens was analyzed. The
      effects on SCLC cell survival and downstream signaling were determined following
      PI3K isoform inhibition by selective inhibitors or downregulation by siRNA.
      RESULTS: Overexpression of the PI3K isoforms p110-alpha and p110-beta and the
      antiapoptotic protein Bcl-2 was shown by immunohistochemistry in primary SCLC
      tissue samples. Targeting the PI3K p110-alpha with RNA interference or selective
      pharmacologic inhibitors resulted in strongly affected cell proliferation of SCLC
      cells in vitro and in vivo, whereas targeting p110-beta was less effective.
      Inhibition of p110-alpha also resulted in increased apoptosis and autophagy,
      which was accompanied by decreased phosphorylation of Akt and components of the
      mTOR pathway, such as the ribosomal S6 protein, and the eukaryotic translation
      initiation factor 4E-binding protein 1. A DNA microarray analysis revealed that
      p110-alpha inhibition profoundly affected the balance of pro- and antiapoptotic
      Bcl-2 family proteins. Finally, p110-alpha inhibition led to impaired SCLC tumor
      formation and vascularization in vivo. CONCLUSION: Together our data show the key
      involvement of the PI3K isoform p110-alpha in the regulation of multiple tumor
      promoting processes in SCLC.

PMID- 23172888
TI  - The Hamilton Rating Scale for Depression: The making of a "gold standard" and the
      unmaking of a chronic illness, 1960-1980.
AB  - OBJECTIVES: To show why and how the Hamilton Rating Scale for Depression became
      the 'Gold Standard' for assessing therapies from the mid-1960s and how it was
      used to frame depression as a short-term and curable illness rather than a
      chronic one. METHODS: My approach is that of the social construction of
      knowledge, identifying the interests, institutional contexts and practices that
      produce knowledge claims and then mapping the social processes of their
      circulation, validation and acceptance. RESULTS: The circulation and validation
      of Hamilton Rating Scale for Depression was relatively slow and it became a 'Gold
      Standard' 'from below', from an emerging consensus amongst psychiatrists
      undertaking clinical trials for depression, which from the 1960s were principally
      with psychopharmaceuticals for short-term illness. Hamilton Rating Scale for
      Depression, drug trials and the construction of depression as non-chronic were
      mutually constituted. DISCUSSION: Hamilton Rating Scale for Depression framed
      depression and its sufferers in new ways, leading psychiatrists to understand
      illness as a treatable episode, rather than a life course condition. As such,
      Hamilton Rating Scale for Depression served the interests of psychiatrists and
      psychiatry in its new era of drug therapy outside the mental hospital. However,
      Hamilton Rating Scale for Depression was a strange kind of 'standard', being
      quite non-standard in the widely varying ways it was used and the meanings given
      to its findings.

PMID- 23172890
TI  - Treatment of pancreatic fibrosis with siRNA against a collagen-specific chaperone
      in vitamin A-coupled liposomes.
AB  - BACKGROUND AND OBJECTIVE: Fibrosis associated with chronic pancreatitis is an
      irreversible lesion that can disrupt pancreatic exocrine and endocrine function.
      Currently, there are no approved treatments for this disease. We previously
      showed that siRNA against collagen-specific chaperone protein gp46, encapsulated
      in vitamin A-coupled liposomes (VA-lip-siRNAgp46), resolved fibrosis in a model
      of liver cirrhosis. This treatment was investigated for pancreatic fibrosis
      induced by dibutyltin dichloride (DBTC) and cerulein in rats. METHODS: Specific
      uptake of VA-lip-siRNAgp46, conjugated with 6'-carboxyfluorescein (FAM) by
      activated pancreatic stellate cells (aPSCs), was analysed by fluorescence
      activated cell sorting (FACS). Intracellular distribution of VA-lip-siRNAgp46-FAM
      was examined by fluorescent microscopy. Suppression of gp46 expression by VA-lip
      siRNAgp46 was assessed by immunoblotting. Collagen synthesis in aPSCs was assayed
      by dye-binding. Specific delivery of VA-lip-siRNAgp46 to aPSCs in DBTC rats was
      verified following intravenous VA-lip-siRNA-FAM and (3)H-VA-lip-siRNAgp46. The
      effect of VA-lip-siRNA on pancreatic histology in DBTC- and cerulein-treated rats
      was determined by Azan-Mallory staining and hydroxyproline content. RESULTS: FACS
      analysis revealed specific uptake of VA-lip-siRNAgp46-FAM through the retinol
      binding protein receptor by aPSCs in vitro. Immunoblotting and collagen assay
      verified knockdown of gp46 and suppression of collagen secretion, respectively,
      by aPSCs after transduction of VA-lip-siRNAgp46. Specific delivery of VA-lip
      siRNAgp46 to aPSCs in fibrotic areas in DBTC rats was confirmed by fluorescence
      and radioactivity 24 h after the final injection. 10 systemic VA-lip-siRNAgp46
      treatments resolved pancreatic fibrosis, and suppressed tissue hydroxyproline
      levels in DBTC- and cerulein-treated rats. CONCLUSION: These data suggest the
      therapeutic potential of the present approach for reversing pancreatic fibrosis.

PMID- 23172889
TI  - Durability of improvement in post-traumatic stress disorder symptoms and absence
      of harmful effects or drug dependency after 3,4-methylenedioxymethamphetamine
      assisted psychotherapy: a prospective long-term follow-up study.
AB  - We report follow-up data evaluating the long-term outcomes for the first
      completed trial of 3,4-methylenedioxymethamphetamine (MDMA)-assisted
      psychotherapy for chronic, treatment-resistant post-traumatic stress disorder
      (PTSD) (Mithoefer et al., 2011). All of the 19 subjects who received MDMA
      assisted treatment in the original trial participated in the long-term follow-up
      (LTFU), with 16 out of 19 completing all of the long-term outcome measures, which
      were administered from 17 to 74 months after the original study's final MDMA
      session (mean = 45.4; SD = 17.3). Our primary outcome measure used was the
      Clinician-Administered PTSD Scale (CAPS). Secondary outcome measures were the
      Impact of Events Scale-Revised (IES-R) and the Neuroticism Extroversion Oppenness
      Personality Inventory-Revised (NEO PI-R) Personality Inventory. We also collected
      a long-term follow-up questionnaire. Results for the 16 CAPS completers showed
      there were no statistical differences between mean CAPS score at LTFU (mean =
      23.7; SD = 22.8) (t (matched) = 0.1; df = 15, p = 0.91) and the mean CAPS score
      previously obtained at Study Exit (mean = 24.6, SD = 18.6). On average, subjects
      maintained statistically and clinically-significant gains in symptom relief,
      although two of these subjects did relapse. It was promising that we found the
      majority of these subjects with previously severe PTSD who were unresponsive to
      existing treatments had symptomatic relief provided by MDMA-assisted
      psychotherapy that persisted over time, with no subjects reporting harm from
      participation in the study.

PMID- 23172891
TI  - Neutralisation of the interleukin-33/ST2 pathway ameliorates experimental colitis
      through enhancement of mucosal healing in mice.
AB  - OBJECTIVE: Inflammatory bowel diseases (IBD) have been intrinsically linked to a
      deregulated cytokine network, but novel therapeutic principles are urgently
      needed. Here we identify the interleukin (IL)-33 and its receptor ST2 as key
      negative regulators of wound healing and permeability in the colon of mice.
      DESIGN: Expression of IL-33 and ST2 was determined by qRT-PCR, ELISA,
      immunohistochemistry and western-blot analysis. Wild-type and St2(-/-) mice were
      used in wound healing experiments and in two experimental models of IBD triggered
      by 2,4,6-trinitrobenzene sulphonic acid or dextran sodium sulphate (DSS).
      Neutralisation of ST2 was performed by using a specific blocking antibody.
      RESULTS: Nuclear localisation and enhanced expression of IL-33 in myofibroblasts
      and enterocytes was linked to disease involvement independently of inflammation,
      while the expression of ST2 was primarily restricted to the colonic epithelia. In
      two experimental models of IBD, genetic ablation of ST2 significantly improved
      signs of colitis, while a sustained epithelial expression of the cyto-protective
      factor connexin-43 was observed in DSS-treated St2-deficient mice. Unexpectedly,
      absence of ST2 in non-hematopoietic cells was sufficient to protect against
      colitis. Consistently, specific inhibition of endogenous ST2-mediated signalling
      by treatment with neutralising antibody improved DSS-induced colitis. In
      addition, IL-33 treatment impaired epithelial barrier permeability in vitro and
      in vivo, whereas absence of ST2 enhanced wound healing response upon acute
      mechanical injury in the colon. CONCLUSIONS: Our study unveiled a novel non
      hematopoietic function of IL-33 in epithelial barrier function and wound healing.
      Therefore, blocking the IL-33/ST2 axis may represent an efficient therapy in IBD.

PMID- 23172892
TI  - Identification of novel in vivo MAP kinase substrates in Arabidopsis thaliana
      through use of tandem metal oxide affinity chromatography.
AB  - Mitogen-activated protein kinase (MPK) cascades are important for eukaryotic
      signal transduction. They convert extracellular stimuli (e.g. some hormones,
      growth factors, cytokines, microbe- or damage-associated molecular patterns) into
      intracellular responses while at the same time amplifying the transmitting
      signal. By doing so, they ensure proper performance, and eventually survival, of
      a given organism, for example in times of stress. MPK cascades function via
      reversible phosphorylation of cascade components MEKKs, MEKs, and MPKs. In plants
      the identity of most MPK substrates remained elusive until now. Here, we provide
      a robust and powerful approach to identify and quantify, with high selectivity,
      site-specific phosphorylation of MPK substrate candidates in the model plant
      Arabidopsis thaliana. Our approach represents a two-step chromatography combining
      phosphoprotein enrichment using Al(OH)(3)-based metal oxide affinity
      chromatography, tryptic digest of enriched phosphoproteins, and TiO(2)-based
      metal oxide affinity chromatography to enrich phosphopeptides from complex
      protein samples. When applied to transgenic conditional gain-of-function
      Arabidopsis plants supporting in planta activation of MPKs, the approach allows
      direct measurement and quantification ex vivo of site-specific phosphorylation of
      several reported and many yet unknown putative MPK substrates in just a single
      experiment.

PMID- 23172893
TI  - Proteomic analysis of temporally stimulated ovarian cancer cells for biomarker
      discovery.
AB  - While ovarian cancer remains the most lethal gynecological malignancy in the
      United States, there are no biomarkers available that are able to predict
      therapeutic responses to ovarian malignancies. One major hurdle in the
      identification of useful biomarkers has been the ability to obtain enough ovarian
      cancer cells from primary tissues diagnosed in the early stages of serous
      carcinomas, the most deadly subtype of ovarian tumor. In order to detect ovarian
      cancer in a state of hyperproliferation, we analyzed the implications of
      molecular signaling cascades in the ovarian cancer cell line OVCAR3 in a temporal
      manner, using a mass-spectrometry-based proteomics approach. OVCAR3 cells were
      treated with EGF(1), and the time course of cell progression was monitored based
      on Akt phosphorylation and growth dynamics. EGF-stimulated Akt phosphorylation
      was detected at 12 h post-treatment, but an effect on proliferation was not
      observed until 48 h post-exposure. Growth-stimulated cellular lysates were
      analyzed for protein profiles between treatment groups and across time points
      using iTRAQ labeling and mass spectrometry. The protein response to EGF treatment
      was identified via iTRAQ analysis in EGF-stimulated lysates relative to vehicle
      treated specimens across the treatment time course. Validation studies were
      performed on one of the differentially regulated proteins, lysosomal-associated
      membrane protein 1 (LAMP-1), in human tissue lysates and ovarian tumor tissue
      sections. Further, tissue microarray analysis was performed to demarcate LAMP-1
      expression across different stages of epithelial ovarian cancers. These data
      support the use of this approach for the efficient identification of tissue-based
      markers in tumor development related to specific signaling pathways. LAMP-1 is a
      promising biomarker for studies of the progression of EGF-stimulated ovarian
      cancers and might be useful in predicting treatment responses involving tyrosine
      kinase inhibitors or EGF receptor monoclonal antibodies.

PMID- 23172896
TI  - Optimizing transition of care through the facilitation of a pharmacist-managed
      deep vein thrombosis treatment program.
AB  - A pharmacist-managed deep vein thrombosis (DVT) treatment program was put into
      operation at Jackson Memorial Hospital in Miami, Florida to provide appropriate
      transition of care to the outpatient setting for patients diagnosed with DVT. A
      postgraduate year 1 pharmacy practice resident partnered with a clinical
      pharmacist to establish and implement the DVT pilot program in the emergency
      department (ED). Once contacted, the pharmacy resident or the clinical pharmacist
      communicated with the ED physician and made recommendations regarding appropriate
      anticoagulation. The pharmacist met with the patient to obtain informed consent
      and provide counseling regarding the anticoagulants. A timely outpatient
      appointment at the pharmacy-managed warfarin clinic was arranged for the patient
      and contact information was exchanged between the patient and the pharmacist. On
      average, patients enrolled in the DVT program from the ED were released 18.29
      hours (+/-7.06) following the time of arrival. Following release from the
      hospital, 91% of patients attended their outpatient follow-up appointment at the
      warfarin clinic. Since the initiation of the DVT program, 1 patient experienced a
      recurrent DVT and major bleed during their treatment course. Due to successful
      implementation of this pharmacist-managed DVT program in the ED, the services
      were subsequently extended to inpatients with DVT. 

PMID- 23172895
TI  - Tobacco smoke exposure in public places and workplaces after smoke-free policy
      implementation: a longitudinal analysis of smoker cohorts in Mexico and Uruguay.
AB  - OBJECTIVE: To determine the prevalence, correlates and changes in secondhand
      smoke (SHS) exposure over the period after comprehensive smoke-free policy
      implementation in two Latin American countries. METHODS: Data were analysed from
      population-based representative samples of adult smokers and recent quitters from
      the 2008 and 2010 waves of the International Tobacco Control Policy Evaluation
      Survey in Mexico (n = 1766 and 1840, respectively) and Uruguay (n = 1379 and
      1411, respectively). Prevalence of SHS exposure was estimated for regulated
      venues, and generalized estimating equations were used to determine correlates of
      SHS exposure. RESULTS: Workplace SHS exposure in the last month was similar
      within and across countries (range: Mexico 20-25%; Uruguay 14-29%). At the most
      recent restaurant visit, SHS exposure was lower where comprehensive smoke-free
      policies were implemented (range: Uruguay 6-9%; Mexico City 5-7%) compared with
      Mexican cities with weaker policies, where exposure remained higher but decreased
      over time (32-17%). At the most recent bar visit, SHS exposure was common (range:
      Uruguay 8-36%; Mexico City 23-31%), although highest in jurisdictions with weaker
      policies (range in other Mexican cities: 74-86%). In Uruguay, males were more
      likely than females to be exposed to SHS across venues, as were younger compared
      with older smokers in Mexico. CONCLUSIONS: Comprehensive smoke-free policies are
      more effective than weaker policies, although compliance in Mexico and Uruguay is
      not as high as desired.

PMID- 23172894
TI  - Proteomic profiling of triple-negative breast carcinomas in combination with a
      three-tier orthogonal technology approach identifies Mage-A4 as potential
      therapeutic target in estrogen receptor negative breast cancer.
AB  - Breast cancer is a very heterogeneous disease, encompassing several intrinsic
      subtypes with various morphological and molecular features, natural history and
      response to therapy. Currently, molecular targeted therapies are available for
      estrogen receptor (ER)(-) and human epidermal growth factor receptor 2 (Her2)
      positive breast tumors. However, a significant proportion of primary breast
      cancers are negative for ER, progesterone receptor (PgR), and Her2, comprising
      the triple negative breast cancer (TNBC) group. Women with TNBC have a poor
      prognosis because of the aggressive nature of these tumors and current lack of
      suitable targeted therapies. As a consequence, the identification of novel
      relevant protein targets for this group of patients is of great importance. Using
      a systematic two dimensional (2D) gel-based proteomic profiling strategy, applied
      to the analysis of fresh TNBC tissue biopsies, in combination with a three-tier
      orthogonal technology (two dimensional PAGE/silver staining coupled with MS, two
      dimensional Western blotting, and immunohistochemistry) approach, we aimed to
      identify targetable protein markers that were present in a significant fraction
      of samples and that could define therapy-amenable sub-groups of TNBCs. We present
      here our results, including a large cumulative database of proteins based on the
      analysis of 78 TNBCs, and the identification and validation of one specific
      protein, Mage-A4, which was expressed in a significant fraction of TNBC and Her2
      positive/ER negative lesions. The high level expression of Mage-A4 in the tumors
      studied allowed the detection of the protein in the tumor interstitial fluids as
      well as in sera. The existence of immunotherapeutics approaches specifically
      targeting this protein, or Mage-A protein family members, and the fact that we
      were able to detect its presence in serum suggest novel management options for
      TNBC and human epidermal growth factor receptor 2 positive/estrogen receptor
      negative patients bearing Mage-A4 positive tumors.

PMID- 23172897
TI  - Novel direct-acting anticoagulants for risk reduction in ACS.
AB  - Acute coronary syndrome (ACS) is a devastating adverse cardiovascular event with
      a massive burden on patient morbility and mortality, as well as the economy.
      Approximately 1.2 million people are hospitalized annually for ACS in the United
      States, with direct medical costs estimated at $150 billion in 2009.
      Rehospitalization is common, often as the result of recurrence of the initial
      event or complications of ACS or its therapy. Thrombosis is central to the
      pathogenesis of ACS. The current standard of care includes dual antiplatelet
      therapy, which reduces platelet activation and aggregation, integral steps for
      forming a thrombus. However, antiplatelet therapy does not prevent continued
      thrombin generation or the deposition of fibrin in the clot and residual risk of
      a recurrent event remains high. New oral anticoagulants offer a mechanism of
      action that is different from and complementary to that of antiplatelet agents.
      The ATLAS ACS-TIMI 51 (Anti-Xa Therapy to Lower Cardiovascular Events in Addition
      to Standard Therapy in Subjects with Acute Coronary Syndrome-Thrombolysis in
      Myocardial Infarction 51) trial, using rivaroxaban, is the first trial of the new
      oral anticoagulants to show a benefit when added to antiplatelet therapy in
      reducing ACS events and mortality. While there was more major bleeding with the
      addition of rivaroxaban, fatal bleeding was not increased. These agents, if added
      to the current standard of care, might substantially reduce the high clinical and
      economic consequences of ACS. 

PMID- 23172899
TI  - Medico-legal and ethical aspects of nasal fractures secondary to assault: do we
      owe a duty of care to advise patients to have a facial x-ray?
AB  - Guidelines advise that x-rays do not contribute to the clinical management of
      simple nasal fractures. However, in cases of simple nasal fracture secondary to
      assault, a facial x-ray may provide additional legal evidence should the victim
      wish to press charges, though there is no published guidance. We examine the
      ethical and medico-legal issues surrounding this controversial area.

PMID- 23172898
TI  - Compliance with inpatient drug use process steps: a cross-sectional observational
      study.
AB  - OBJECTIVES: The aim was to compare nursing staff compliance over the years, per
      health care unit, and per drug use process step. METHODS: Compliance assessment
      was performed by nursing consultants with direct observation of the registered
      nurses and nursing assistants during the performance of 7 steps of the drug use
      process. A total of 36 compliance criteria were developed. The compliance to drug
      use process criteria was measured in 2007 (Prephase), 2008 (post 1), and 2011
      (post 2). Totally, 10 health care units were evaluated, with a minimum of 10
      doses evaluated per health care unit, including a minimum of 5 parental doses and
      a total of 100 nurses observed. RESULTS: A total of 142 nurses were observed in
      the prephase, 140 nurses in the post 1 phase, and 98 in the post 2 phase (90%
      regular staff and 10% float staff). The overall compliance rates went from 77% in
      2007 up to 87% in 2008 and down to 78% in 2011. CONCLUSIONS: This cross-sectional
      observational study revealed a significant difference in the drug use process
      compliance in terms of drug preparation and drug administration for inpatients at
      the bedside, between 2007 and 2011.

PMID- 23172900
TI  - Best interests and the sanctity of life after W v M.
AB  - The case of W v M and Others, in which the court rejected an application to
      withdraw artificial nutrition and hydration from a woman in a minimally conscious
      state, raises a number of profoundly important medico-legal issues. This article
      questions whether the requirement to respect the autonomy of incompetent
      patients, under the Mental Capacity Act 2005, is being unjustifiably disregarded
      in order to prioritise the sanctity of life. When patients have made informal
      statements of wishes and views, which clearly--if not precisely--apply to their
      present situation, judges should not feel free to usurp such expressions of
      autonomy unless there are compelling reasons for so doing.

PMID- 23172901
TI  - Immunological follow-up of patients with neuromyelitis optica: is there a good
      biomarker?
AB  - A serial assessment of biomarkers related to disease activity could be clinically
      useful in some autoimmune diseases. Neuromyelitis optica (NMO) is a severe
      inflammatory disease of the optic nerves and spinal cord that can be associated
      with lupus erythematosus, Sjogren syndrome or myasthenia gravis. In this review,
      we discuss the existing data on the use of biomarkers of disease activity in NMO.
      A specific and pathogenic antibody (Ab) directed against aquaporin 4 (AQP4) was
      recently discovered in this disease. The relapses were frequently accompanied by
      a rise and immunosuppressive therapy by a decrease in serum anti-AQP4 Ab
      concentrations. However, this association is not strong enough to justify
      treatment changes based only on anti-AQP4 Ab level variations. This parameter
      might be helpful as a longitudinal biomarker but only if a threshold inducing a
      relapse and justifying a switch in therapy can be established. A link between
      disease severity and serum cytotoxicity against AQP4-expressing cells was
      proposed but has not yet been confirmed. Finally, the assessment of T cell
      immunity against AQP4 and specific cytokines could be future directions for
      research.

PMID- 23172902
TI  - Hemophagocytic lymphohistiocytosis--a diagnostic dilemma: two cases and review.
AB  - Hemophagocytic lymphohistiocytosis (HLH) is a severe inflammatory disorder
      characterized by activation and proliferation of lymphocytes and histiocytes with
      cytokine release and uncontrolled hemophagocytosis, especially late in the course
      of the disease. Clinical features include relapsing fevers, hepatosplenomegaly,
      cytopenias, lymphadenopathy, and coagulopathy. The diagnosis can be challenging,
      as the early signs and symptoms are nonspecific and no specific laboratory tests
      exist. This syndrome is frequently not recognized and has a significant mortality
      rate. Typical scenarios in which HLH should be considered include mononucleosis
      (fever, hepatosplenomegaly, and lymphadenopathy) in an infant or young child,
      aseptic meningitis associated with cytopenias, or a viral syndrome-like illness
      with cytopenias and lymphadenopathy or splenomegaly, for example. Our approach
      includes measuring a ferritin level as a screening tool early in the course of
      such an illness. Two cases of HLH are reviewed, illustrating the frequent
      complexity of these cases and potential pitfalls to making a prompt diagnosis.

PMID- 23172903
TI  - Baby unplugged: a novel, market-based approach to reducing screen time and
      promoting healthy alternatives.
AB  - The issue of electronic media use by young children is increasingly important in
      pediatrics, a major risk factor for numerous chronic conditions. Despite
      guidelines in place since 1999, screen time is on the rise, aided by new formats
      removing practically all barriers of use. Key drivers are technological allure,
      confusion about developmental readiness, and perception of educational value,
      fueled by potent marketing. This article describes the development of Baby
      Unplugged, a series of children's board books celebrating "old-school," screen
      free childhood. Written by a pediatrician who also owns a children's bookstore,
      the books were inspired and informed by advocacy projects in the areas of media
      use and early literacy as a pediatric resident. They reinforce AAP Electronic
      Media Guidelines, notably discouraging screen-based media under 2 years old,
      largely by encouraging healthy, fun alternatives. Examples include Pets, Book,
      and Yard. Multi-sensorial exploration and parent-child engagement are emphasized
      in a non-prescriptive way, featuring gender and ethnic diversity and activities
      that are accessible and inexpensive. The author describes challenges faced by
      pediatricians providing anticipatory guidance for media use, given limited time
      and resources and the perception that we are out of touch. This is heightened by
      oft-deceptive marketing of screen-based products more likely to be perceived as
      "cool." Reach Out and Read is cited as an example of a successful, "cool"
      intervention, though limited to select populations. Baby Unplugged takes advocacy
      to the marketplace, where the screen time battle is being lost.

PMID- 23172904
TI  - An adolescent found unconscious.

PMID- 23172905
TI  - Sterile cerebrospinal fluid pleocytosis in an infant with appendicitis.

PMID- 23172906
TI  - An adolescent female with fever, rash, and arthralgias.

PMID- 23172907
TI  - Pulse steroid therapy inhibits murine subglottic granulation.
AB  - OBJECTIVE: Using a functional model of airway granulation tissue in subglottic
      stenosis, we investigated changes in inflammatory markers within granulation
      tissue in response to intraperitoneal dexamethasone injections. Changes in
      inflammatory markers will allow us to identify potential targets for
      immunological therapy. STUDY DESIGN: Institutional Animal Care and Use Committee
      approved animal study. SETTING: Philadelphia Veterans Administration Medical
      Center animal research facility. SUBJECTS AND METHODS: Laryngotracheal complexes
      of donor mice underwent direct airway injury and were transplanted into
      subcutaneous tissue of 19 recipient mice in 2 groups: steroid treated and
      untreated, with sample sizes of 10 and 9, respectively. The steroid-treated arm
      received intraperitoneal injection of dexamethasone for 3 weeks. Laryngotracheal
      complexes were then harvested, and granulation formation was measured. The
      messenger RNA (mRNA) expression of transforming growth factor (TGF)-beta(1) and
      interleukin (IL)-1 was quantified. RESULTS: At 3 weeks posttransplantation, there
      were statistically significant differences in observable granulation formation as
      well as mRNA expression of TGF-beta(1) and IL-1beta in all groups within the
      steroid treated arm as compared with the untreated arm. CONCLUSIONS: Systemic
      steroids have been used to prevent formation of granulation tissue and subglottic
      stenosis. However, the study of the immunologic markers and the corresponding
      changes with steroid treatment has not been well studied in animal models. Using
      a previously described novel murine model, we begin to delineate inflammatory
      markers that can be applied for potential therapeutic targets.

PMID- 23172908
TI  - Reduction of polyglutamine toxicity by TDP-43, FUS and progranulin in
      Huntington's disease models.
AB  - The DNA/RNA binding proteins TAR DNA-binding protein 43 (TDP-43) and fused-in
      sarcoma (FUS) are genetically linked to amyotrophic lateral sclerosis and
      frontotemporal lobar dementia, while the inappropriate cytoplasmic accumulations
      of TDP-43 and FUS are observed in a growing number of late-onset pathologies
      including spinocerebellar ataxia 3, Alzheimer's and Huntington's diseases (HD).
      To investigate if TDP-43 and FUS contribute to neurodegenerative phenotypes, we
      turned to a genetically accessible Caenorhabditis elegans model of polyglutamine
      toxicity. In C. elegans, we observe that genetic loss-of-function mutations for
      nematode orthologs of TDP-43 or FUS reduced behavioral defects and
      neurodegeneration caused by huntingtin exon-1 with expanded polyglutamines.
      Furthermore, using striatal cells from huntingtin knock-in mice we observed that
      small interfering ribonucleic acid (siRNA) against TDP-43 or FUS reduced cell
      death caused by mutant huntingtin. Moreover, we found that TDP-43 and the
      survival factor progranulin (PGRN) genetically interact to regulate polyglutamine
      toxicity in C. elegans and mammalian cells. Altogether our data point towards a
      conserved function for TDP-43 and FUS in promoting polyglutamine toxicity and
      that delivery of PGRN may have therapeutic benefits.

PMID- 23172909
TI  - Ataxin-2 interacts with FUS and intermediate-length polyglutamine expansions
      enhance FUS-related pathology in amyotrophic lateral sclerosis.
AB  - Fused in sarcoma (FUS) is mutated in both sporadic amyotrophic lateral sclerosis
      (ALS) and familial ALS patients. The mechanisms underlying neurodegeneration are
      not fully understood, but FUS redistributes from the nucleus to the cytoplasm in
      affected motor neurons, where it triggers endoplasmic reticulum (ER) stress.
      Ataxin-2 is a polyglutamine protein which normally contains 22 repeats, but
      expanded repeats (>34) are found in Spinocerebellar Ataxia type 2. Recently
      ataxin-2 with intermediate length repeats (27-33) was found to increase the risk
      of ALS. Here we show that ataxin-2 with an ALS-linked intermediate length repeat
      (Q31) is a potent modifier of FUS pathology in cellular disease models.
      Translocation of FUS to the cytoplasm and ER stress were significantly enhanced
      by co-expression of mutant FUS with ataxin-2 Q31. Ataxin-2 also co-localized with
      FUS in sporadic and FUS-linked familial ALS patient motor neurons, co
      precipitated with FUS in ALS spinal cord lysates, and co-localized with FUS in
      the ER-Golgi compartments in neuronal cell lines. Fragmentation of the Golgi
      apparatus is linked to neurodegeneration in ALS and here we show that Golgi
      fragmentation is induced in cells expressing mutant FUS. Moreover, Golgi
      fragmentation was enhanced, and the early stages of apoptosis were triggered,
      when ataxin-2 Q31 was co-expressed with mutant FUS. These findings describe new
      cellular mechanisms linking ALS with ataxin-2 intermediate length polyQ
      expansions and provide further evidence linking disruption to ER-Golgi
      compartments and FUS pathology in ALS.

PMID- 23172910
TI  - Effect of powered gait orthosis on walking in individuals with paraplegia.
AB  - BACKGROUND: The important purpose of a powered gait orthosis is to provide active
      joint movement for patients with spinal cord injury. OBJECTIVES: The aim of this
      study was to clarify the effect of a powered gait orthosis on the kinematics and
      temporal-spatial parameters in paraplegics with spinal cord injury. STUDY DESIGN:
      Quasi-experimental. METHODS: Four spinal cord injury individuals experienced gait
      training with a powered gait orthosis for a minimum of 6 weeks prior to
      participating in the following walking trials: walking with an isocentric
      reciprocating gait orthosis and walking with both separate and synchronized
      movements with actuated orthotic hip and knee joints in a powered gait orthosis.
      Specific parameters were calculated and compared for each of the test conditions.
      RESULTS: Using separate and synchronized actuated movement of the hip and knee
      joints in the powered gait orthosis increased gait speed and step length and
      reduced lateral and vertical compensatory motions when compared to the isocentric
      reciprocating gait orthosis, but there were no significant differences in these
      parameters. Using the new powered gait orthosis improved knee and hip joint
      kinematics. CONCLUSIONS: The powered gait orthosis increased speed and step
      length as well as hip and knee joint kinematics and reduced the vertical and
      lateral compensatory motions compared to an isocentric reciprocating gait
      orthosis in spinal cord injury patients. CLINICAL RELEVANCE: This new powered
      gait orthosis has the potential to improve hip and knee joint kinematics, the
      temporal-spatial parameters of gait in spinal cord injury patients walking.

PMID- 23172911
TI  - The effort to make mosaic analysis a household tool.
AB  - The analysis of genetic mosaics, in which an animal carries populations of cells
      with differing genotypes, is a powerful tool for understanding developmental and
      cell biology. In 1990, we set out to improve the methods used to make genetic
      mosaics in Drosophila by taking advantage of recently developed approaches for
      genome engineering. These efforts led to the work described in our 1993
      Development paper.

PMID- 23172912
TI  - Importance of the pluripotency factor LIN28 in the mammalian nucleolus during
      early embryonic development.
AB  - The maternal nucleolus is required for proper activation of the embryonic genome
      (EGA) and early embryonic development. Nucleologenesis is characterized by the
      transformation of a nucleolar precursor body (NPB) to a mature nucleolus during
      preimplantation development. However, the function of NPBs and the involved
      molecular factors are unknown. We uncover a novel role for the pluripotency
      factor LIN28, the biological significance of which was previously demonstrated in
      the reprogramming of human somatic cells to induced pluripotent stem (iPS) cells.
      Here, we show that LIN28 accumulates at the NPB and the mature nucleolus in mouse
      preimplantation embryos and embryonic stem cells (ESCs), where it colocalizes
      with the nucleolar marker B23 (nucleophosmin 1). LIN28 has nucleolar localization
      in non-human primate (NHP) preimplantation embryos, but is cytoplasmic in NHP
      ESCs. Lin28 transcripts show a striking decline before mouse EGA, whereas LIN28
      protein localizes to NPBs at the time of EGA. Following knockdown with a Lin28
      morpholino, the majority of embryos arrest between the 2- and 4-cell stages and
      never develop to morula or blastocyst. Lin28 morpholino-injected embryos arrested
      at the 2-cell stage were not enriched with nucleophosmin at presumptive NPB
      sites, indicating that functional NPBs were not assembled. Based on these
      results, we propose that LIN28 is an essential factor of nucleologenesis during
      early embryonic development.

PMID- 23172913
TI  - Non-autonomous crosstalk between the Jak/Stat and Egfr pathways mediates Apc1
      driven intestinal stem cell hyperplasia in the Drosophila adult midgut.
AB  - Inactivating mutations within adenomatous polyposis coli (APC), a negative
      regulator of Wnt signaling, are responsible for most sporadic and hereditary
      forms of colorectal cancer (CRC). Here, we use the adult Drosophila midgut as a
      model system to investigate the molecular events that mediate intestinal
      hyperplasia following loss of Apc in the intestine. Our results indicate that the
      conserved Wnt target Myc and its binding partner Max are required for the
      initiation and maintenance of intestinal stem cell (ISC) hyperproliferation
      following Apc1 loss. Importantly, we find that loss of Apc1 leads to the
      production of the interleukin-like ligands Upd2/3 and the EGF-like Spitz in a Myc
      dependent manner. Loss of Apc1 or high Wg in ISCs results in non-cell-autonomous
      upregulation of upd3 in enterocytes and subsequent activation of Jak/Stat
      signaling in ISCs. Crucially, knocking down Jak/Stat or Spitz/Egfr signaling
      suppresses Apc1-dependent ISC hyperproliferation. In summary, our results uncover
      a novel non-cell-autonomous interplay between Wnt/Myc, Egfr and Jak/Stat
      signaling in the regulation of intestinal hyperproliferation. Furthermore, we
      present evidence suggesting potential conservation in mouse models and human CRC.
      Therefore, the Drosophila adult midgut proves to be a powerful genetic system to
      identify novel mediators of APC phenotypes in the intestine.

PMID- 23172914
TI  - Emergence of embryonic pattern through contact inhibition of locomotion.
AB  - The pioneering cell biologist Michael Abercrombie first described the process of
      contact inhibition of locomotion more than 50 years ago when migrating
      fibroblasts were observed to rapidly change direction and migrate away upon
      collision. Since then, we have gleaned little understanding of how contact
      inhibition is regulated and only lately observed its occurrence in vivo. We
      recently revealed that Drosophila macrophages (haemocytes) require contact
      inhibition for their uniform embryonic dispersal. Here, to investigate the role
      that contact inhibition plays in the patterning of haemocyte movements, we have
      mathematically analysed and simulated their contact repulsion dynamics. Our data
      reveal that the final pattern of haemocyte distribution, and the details and
      timing of its formation, can be explained by contact inhibition dynamics within
      the geometry of the Drosophila embryo. This has implications for morphogenesis in
      general as it suggests that patterns can emerge, irrespective of external cues,
      when cells interact through simple rules of contact repulsion.

PMID- 23172915
TI  - Residual body removal during spermatogenesis in C. elegans requires genes that
      mediate cell corpse clearance.
AB  - Generation of spermatozoa involves segregation of most of the cytoplasm into
      residual bodies, which are detached from spermatids and eliminated in mammals.
      However, the molecular and cellular mechanism underlying the removal of residual
      bodies remains largely unknown. Here, we demonstrate that during C. elegans
      spermatogenesis residual bodies are engulfed and degraded by gonadal sheath
      cells, a process that uses the same set of genes underlying apoptotic cell
      removal. The two partially redundant engulfment pathways that clear cell corpses
      also mediate phagocytosis of residual bodies, possibly by recognizing the 'eat
      me' signal phosphatidylserine exposed on the surface. The residual body
      containing phagosome undergoes a maturation process involving sequential steps
      including dynamic coating with PtdIns(3)P and association of RAB small GTPases.
      The genetic hierarchy of residual body removal in hermaphrodites is similar to
      that of cell corpse clearance, but male residual body removal involves a distinct
      hierarchy, with differential use of the engulfment genes. Efficient removal of
      residual bodies regulates the number of spermatids and effective transfer of
      spermatids during male matings. Our results indicate that a similar molecular
      mechanism is employed for the removal of residual bodies and apoptotic cell
      corpses in C. elegans.

PMID- 23172916
TI  - Regulation of retinal interneuron subtype identity by the Iroquois homeobox gene
      Irx6.
AB  - Interneuronal subtype diversity lies at the heart of the distinct molecular
      properties and synaptic connections that shape the formation of the neuronal
      circuits that are necessary for the complex spatial and temporal processing of
      sensory information. Here, we investigate the role of Irx6, a member of the
      Iroquois homeodomain transcription factor family, in regulating the development
      of retinal bipolar interneurons. Using a knock-in reporter approach, we show
      that, in the mouse retina, Irx6 is expressed in type 2 and 3a OFF bipolar
      interneurons and is required for the expression of cell type-specific markers in
      these cells, likely through direct transcriptional regulation. In Irx6 mutant
      mice, presumptive type 3a bipolar cells exhibit an expansion of their axonal
      projection domain to the entire OFF region of the inner plexiform layer, and
      adopt molecular features of both type 2 and 3a bipolar cells, highlighted by the
      ectopic upregulation of neurokinin 3 receptor (Nk3r) and Vsx1. These findings
      reveal Irx6 as a key regulator of type 3a bipolar cell identity that prevents
      these cells from adopting characteristic features of type 2 bipolar cells.
      Analysis of the Irx6;Vsx1 double null retina suggests that the terminal
      differentiation of type 2 bipolar cells is dependent on the combined expression
      of the transcription factors Irx6 and Vsx1, but also points to the existence of
      Irx6;Vsx1-independent mechanisms in regulating OFF bipolar subtype-specific gene
      expression. This work provides insight into the generation of neuronal subtypes
      by revealing a mechanism in which opposing, yet interdependent, transcription
      factors regulate subtype identity.

PMID- 23172917
TI  - The differentiation and movement of presomitic mesoderm progenitor cells are
      controlled by Mesogenin 1.
AB  - Somites are formed from the presomitic mesoderm (PSM) and give rise to the axial
      skeleton and skeletal muscles. The PSM is dynamic; somites are generated at the
      anterior end, while the posterior end is continually renewed with new cells
      entering from the tailbud progenitor region. Which genes control the conversion
      of tailbud progenitors into PSM and how is this process coordinated with cell
      movement? Using loss- and gain-of-function experiments and heat-shock transgenics
      we show in zebrafish that the transcription factor Mesogenin 1 (Msgn1), acting
      with Spadetail (Spt), has a central role. Msgn1 allows progression of the PSM
      differentiation program by switching off the progenitor maintenance genes ntl,
      wnt3a, wnt8 and fgf8 in the future PSM cells as they exit from the tailbud, and
      subsequently induces expression of PSM markers such as tbx24. msgn1 is itself
      positively regulated by Ntl/Wnt/Fgf, creating a negative-feedback loop that might
      be crucial to regulate homeostasis of the progenitor population until
      somitogenesis ends. Msgn1 drives not only the changes in gene expression in the
      nascent PSM cells but also the movements by which they stream out of the tailbud
      into the PSM. Loss of Msgn1 reduces the flux of cells out of the tailbud,
      producing smaller somites and an enlarged tailbud, and, by delaying exhaustion of
      the progenitor population, results in supernumerary tail somites. Through its
      combined effects on gene expression and cell movement, Msgn1 (with Spt) plays a
      key role both in genesis of the paraxial mesoderm and in maintenance of the
      progenitor population from which it derives.

PMID- 23172918
TI  - Macrophage migration inhibitory factor acts as a neurotrophin in the developing
      inner ear.
AB  - This study is the first to demonstrate that macrophage migration inhibitory
      factor (MIF), an immune system 'inflammatory' cytokine that is released by the
      developing otocyst, plays a role in regulating early innervation of the mouse and
      chick inner ear. We demonstrate that MIF is a major bioactive component of the
      previously uncharacterized otocyst-derived factor, which directs initial neurite
      outgrowth from the statoacoustic ganglion (SAG) to the developing inner ear.
      Recombinant MIF acts as a neurotrophin in promoting both SAG directional neurite
      outgrowth and neuronal survival and is expressed in both the developing and
      mature inner ear of chick and mouse. A MIF receptor, CD74, is found on both
      embryonic SAG neurons and adult mouse spiral ganglion neurons. Mif knockout mice
      are hearing impaired and demonstrate altered innervation to the organ of Corti,
      as well as fewer sensory hair cells. Furthermore, mouse embryonic stem cells
      become neuron-like when exposed to picomolar levels of MIF, suggesting the
      general importance of this cytokine in neural development.

PMID- 23172919
TI  - Flavonoid apigenin is an inhibitor of the NAD+ ase CD38: implications for
      cellular NAD+ metabolism, protein acetylation, and treatment of metabolic
      syndrome.
AB  - Metabolic syndrome is a growing health problem worldwide. It is therefore
      imperative to develop new strategies to treat this pathology. In the past years,
      the manipulation of NAD(+) metabolism has emerged as a plausible strategy to
      ameliorate metabolic syndrome. In particular, an increase in cellular NAD(+)
      levels has beneficial effects, likely because of the activation of sirtuins.
      Previously, we reported that CD38 is the primary NAD(+)ase in mammals. Moreover,
      CD38 knockout mice have higher NAD(+) levels and are protected against obesity
      and metabolic syndrome. Here, we show that CD38 regulates global protein
      acetylation through changes in NAD(+) levels and sirtuin activity. In addition,
      we characterize two CD38 inhibitors: quercetin and apigenin. We show that
      pharmacological inhibition of CD38 results in higher intracellular NAD(+) levels
      and that treatment of cell cultures with apigenin decreases global acetylation as
      well as the acetylation of p53 and RelA-p65. Finally, apigenin administration to
      obese mice increases NAD(+) levels, decreases global protein acetylation, and
      improves several aspects of glucose and lipid homeostasis. Our results show that
      CD38 is a novel pharmacological target to treat metabolic diseases via NAD(+)
      dependent pathways.

PMID- 23172920
TI  - RAGE deficiency improves postinjury sciatic nerve regeneration in type 1 diabetic
      mice.
AB  - Peripheral neuropathy and insensate limbs and digits cause significant morbidity
      in diabetic individuals. Previous studies showed that deletion of the receptor
      for advanced end-glycation products (RAGE) in mice was protective in long-term
      diabetic neuropathy. Here, we tested the hypothesis that RAGE suppresses
      effective axonal regeneration in superimposed acute peripheral nerve injury
      attributable to tissue-damaging inflammatory responses. We report that deletion
      of RAGE, particularly in diabetic mice, resulted in significantly higher
      myelinated fiber densities and conduction velocities consequent to acute sciatic
      nerve crush compared with wild-type control animals. Consistent with key roles
      for RAGE-dependent inflammation, reconstitution of diabetic wild-type mice with
      RAGE-null versus wild-type bone marrow resulted in significantly improved axonal
      regeneration and restoration of function. Diabetic RAGE-null mice displayed
      higher numbers of invading macrophages in the nerve segments postcrush compared
      with wild-type animals, and these macrophages in diabetic RAGE-null mice
      displayed greater M2 polarization. In vitro, treatment of wild-type bone marrow
      derived macrophages with advanced glycation end products (AGEs), which accumulate
      in diabetic nerve tissue, increased M1 and decreased M2 gene expression in a RAGE
      dependent manner. Blockade of RAGE may be beneficial in the acute complications
      of diabetic neuropathy, at least in part, via upregulation of regeneration
      signals.

PMID- 23172921
TI  - CD36 and Na/K-ATPase-alpha1 form a proinflammatory signaling loop in kidney.
AB  - Proatherogenic, hyperlipidemic states demonstrate increases in circulating
      ligands for scavenger receptor CD36 (eg, oxidized low-density lipoprotein
      [oxLDL]) and the Na/K-ATPase (eg, cardiotonic steroids). These factors increase
      inflammation, oxidative stress, and progression of chronic kidney disease. We
      hypothesized that diet-induced obesity and hyperlipidemia potentiate a CD36/Na/K
      ATPase-dependent inflammatory paracrine loop between proximal tubule cells (PTCs)
      and their associated macrophages and thereby facilitate development of chronic
      inflammation and tubulointerstitial fibrosis. ApoE(-/-) and apoE(-/-)/cd36(-/-)
      mice were fed a high-fat diet for <=32 weeks and examined for physiologic and
      histologic changes in renal function. Compared with apoE(-/-), apoE(-/-)/cd36(-/
      ) mice had improved creatinine clearance and blood pressure which corresponded
      histologically with less glomerular and tubulointerstitial macrophage
      accumulation, foam cell formation, oxidant stress, and interstitial fibrosis.
      Coimmunopreciptation and a cell surface fluorescence-based crosslinking assay
      showed that CD36 and Na/K-ATPase alpha-1 colocalized in PTCs and macrophages, and
      this association was increased by oxLDL or the cardiotonic steroid ouabain. OxLDL
      and ouabain also increased activation of Src and Lyn in PTCs. Cell-free
      conditioned medium from PTCs treated with oxLDL or ouabain increased macrophage
      migration. OxLDL, ouabain, or plasma isolated from high-fat diet-fed mice
      stimulated reactive oxygen species production in PTCs, which was inhibited by N
      acetyl-cysteine, apocynin, or Na/K-ATPase alpha-1 knockdown. These data suggest
      that ligands generated in hyperlipidemic states activate CD36 and the Na/K-ATPase
      and potentiate an inflammatory signaling loop involving PTCs and their associated
      macrophages, which facilitates the development of chronic inflammation, oxidant
      stress, and fibrosis underlying the renal dysfunction common to proatherogenic,
      hyperlipidemic states.

PMID- 23172922
TI  - Ganglion-specific impairment of the norepinephrine transporter in the
      hypertensive rat.
AB  - Hypertension is associated with enhanced cardiac sympathetic transmission,
      although the exact mechanisms underlying this are still unknown. We hypothesized
      that defective function of the norepinephrine uptake transporter (NET) may
      contribute to the sympathetic phenotype of the spontaneously hypertensive rat,
      and that this may occur before the development of hypertension itself. The
      dynamic kinetics of NET were monitored temporally using a novel fluorescent assay
      of the transporter in cultured postganglionic sympathetic neurons from the
      cardiac stellate ganglion, the superior cervical ganglion, the celiac
      ganglia/superior mesenteric ganglia, and the renal sympathetic chain. All NET
      activity was blocked by desipramine. NET rate was significantly impaired in
      cardiac stellate sympathetic neurons from the prehypertensive spontaneously
      hypertensive rat compared with age-matched normotensive Wistar-Kyoto rats. A
      similar response was seen in hypertensive spontaneously hypertensive rats
      stellate sympathetic neurons. However, no reduction in transporter rate was
      observed at either age in the other major noncardiac sympathetic ganglia.
      Depolarization of cardiac stellate neurons by electrical field stimulation
      further potentiated the difference in transporter rate observed between the
      hypertensive and normotensive rats at both developmental ages. In conclusion,
      dysregulation of the norepinephrine transporter in the hypertensive rat is
      ganglion-specific, where NET impairment in the stellate neurons may contribute to
      the increased cardiac norepinephrine spillover seen in hypertension.

PMID- 23172925
TI  - Targeted neuronal nitric oxide synthase transgene delivery into stellate neurons
      reverses impaired intracellular calcium transients in prehypertensive rats.
AB  - Hypertension is associated with the early onset of cardiac sympathetic
      hyperresponsiveness and enhanced intracellular Ca(2+) concentration [Ca(2+)](i)
      in sympathetic neurons from both prehypertensive and hypertensive, spontaneously
      hypertensive rats (SHRs). Oxidative stress is a hallmark of hypertension,
      therefore, we tested the hypothesis that the inhibitory action of the nitric
      oxide-cGMP pathway on [Ca(2+)](i) transients is impaired in cardiac sympathetic
      neurons from the SHR. Stellate ganglia were isolated from young prehypertensive
      SHRs and age-matched normotensive Wistar-Kyoto rats. [Ca(2+)](i) was measured by
      ratiometric fluorescence imaging. Neurons from the prehypertensive SHR ganglia
      had a significantly higher depolarization evoked [Ca(2+)](i) transient that was
      also associated with decreased expression of neuronal nitric oxide synthase
      (nNOS), beta1 subunit of soluble guanylate cyclase and cGMP when compared with
      the Wistar-Kyoto rat ganglia. Soluble guanylate cyclase inhibition or nNOS
      inhibition increased [Ca(2+)](i) in the Wistar-Kyoto rats but had no effect in
      SHR neurons. A nitric oxide donor decreased [Ca(2+)](i) in both sets of neurons,
      although this was markedly less in the SHR. A novel noradrenergic cell specific
      vector (Ad.PRSx8-nNOS/Cherry) or its control vector (Ad.PRSx8-Cherry) was
      expressed in sympathetic neurons. In the SHR, Ad.PRSx8-nNOS/Cherry-treated
      neurons had a significantly reduced peak [Ca(2+)](i) transient that was
      associated with increased tissue levels of nNOS protein and cGMP concentration
      compared with gene transfer of Ad.PRSx8-Cherry alone. nNOS inhibition
      significantly increased [Ca(2+)](i) after Ad.PRSx8-nNOS/Cherry expression. We
      conclude that artificial upregulation of stellate sympathetic nNOS via targeted
      gene transfer can directly attenuate intracellular Ca(2+) and may provide a novel
      method for decreasing enhanced cardiac sympathetic neurotransmission.

PMID- 23172923
TI  - Aortic pulse wave velocity predicts focal white matter hyperintensities in a
      biracial cohort of older adults.
AB  - Although the cross-sectional relationship of arterial stiffness with cerebral
      small vessel disease is consistently shown in middle-aged and young-old adults,
      it is less clear whether these associations remain significant over time in very
      old adults. We hypothesize that arterial stiffness is longitudinally associated
      with white matter characteristics, and associations are stronger within watershed
      areas. Neuroimaging was obtained in 2006-2008 from 303 elderly (mean age 82.9
      years, 59% women, 41% black) with pulse wave velocity (PWV) measures in 1997
      1998. Multivariable regression models estimated the coefficients for PWV (cm/sec)
      in relationship to presence, severity, and spatial distribution of white matter
      hyperintensities (WMH), gray matter volume, and fractional anisotropy from
      diffusion tensor, adjusting for demographic, cardiovascular risk factors, and
      diseases from 1997-1998 to 2006-2008. Higher PWV in 1997-1998 was associated with
      greater WMH volume in 2006-2008 within the left superior longitudinal fasciculus
      (age and total brain WMH adjusted, P=0.023), but not with WMH in other tracts or
      with fractional anisotropy or gray matter volume from total brain (P>0.2).
      Associations were stronger in blacks than in whites, remaining significant in
      fully adjusted models. Elderly with WMH in tracts related to processing speed and
      memory are more likely to have had higher PWV values 10 years prior, before
      neuroimaging data being available. Future studies should address whether arterial
      stiffness can serve as an early biomarker of covert brain structural
      abnormalities and whether early arterial stiffness control can promote successful
      brain aging, especially in black elderly.

PMID- 23172926
TI  - Ambulatory blood pressure monitoring trumps estimated glomerular filtration rate
      in predicting cardiovascular risk in low-risk populations.

PMID- 23172924
TI  - Excessive leukotriene B4 in nucleus tractus solitarii is prohypertensive in
      spontaneously hypertensive rats.
AB  - Inflammation within the brain stem microvasculature has been associated with
      chronic cardiovascular diseases. We found that the expression of several enzymes
      involved in arachidonic acid-leukotriene B4 (LTB4) production was altered in
      nucleus tractus solitarii (NTS) of spontaneously hypertensive rat (SHR). LTB4
      produced from arachidonic acid by 5-lipoxygenase is a potent chemoattractant of
      leukocytes. Leukotriene B4-12-hydroxydehydrogenase (LTB4-12-HD), which degrades
      LTB4, was downregulated in SHR rats compared with that in Wistar-Kyoto rats.
      Quantitative real-time PCR revealed that LTB4-12-HD was reduced by 63% and 58% in
      the NTS of adult SHR and prehypertensive SHR, respectively, compared with that in
      age-matched Wistar-Kyoto rats (n=6). 5-lipoxygenase gene expression was
      upregulated in the NTS of SHR (~50%; n=6). LTB4 levels were increased in the NTS
      of the SHR, (17%; n=10, P<0.05). LTB4 receptors BLT1 (but not BLT2) were
      expressed on astroglia in the NTS but not neurons or vessels. Microinjection of
      LTB4 into the NTS of Wistar-Kyoto rats increased both leukocyte adherence and
      arterial pressure for over 4 days (peak: +15 mm Hg; P<0.01). In contrast,
      blockade of NTS BLT1 receptors lowered blood pressure in the SHR (peak: -13 mm
      Hg; P<0.05) but not in Wistar-Kyoto rats. Thus, excessive amounts of LTB4 in NTS
      of SHR, possibly as a result of upregulation of 5-lipoxygenase and downregulation
      of LTB4-12-HD, can induce inflammation. Because blockade of NTS BLT1 receptors
      lowered arterial pressure in the SHR, their endogenous activity may contribute to
      the hypertensive state of this rodent model. Thus, inflammatory reactions in the
      brain stem are causally associated with neurogenic hypertension.

PMID- 23172927
TI  - The carotid body as a therapeutic target for the treatment of sympathetically
      mediated diseases.

PMID- 23172929
TI  - Substantial reduction in single sympathetic nerve firing after renal denervation
      in patients with resistant hypertension.
AB  - Renal denervation (RDN) has been shown to reduce blood pressure (BP) and muscle
      sympathetic nerve activity (MSNA) in patients with resistant hypertension. The
      mechanisms underlying sympathetic neural inhibition are unknown. We examined
      whether RDN differentially influences the sympathetic discharge pattern of
      vasoconstrictor neurons in patients with resistant hypertension. Standardized
      office BP, single-unit MSNA, and multi-unit MSNA were obtained at baseline and at
      3-month follow-up in 35 patients with resistant hypertension. Twenty-five
      patients underwent RDN, and 10 patients underwent repeated measurements without
      RDN (non-RDN). Baseline BP averaged 164/93 mm Hg (RDN) and 164/87 mm Hg (non-RDN)
      despite use of an average of 4.8 +/- 0.4 and 4.4 +/- 0.5 antihypertensive drugs,
      respectively. Mean office BP decreased significantly by -13/-6 mm Hg for systolic
      BP (P<0.001) and diastolic BP (P<0.05) with RDN but not in non-RDN at 3-month
      follow-up. RDN moderately decreased multi-unit MSNA (79 +/- 3 versus 73 +/- 4
      bursts/100 heartbeats; P<0.05), whereas all properties of single-unit MSNA
      including firing rates of individual vasoconstrictor fibers (43 +/- 5 versus 27
      +/- 3 spikes/100 heartbeats; P<0.01), firing probability (30 +/- 2 versus 22 +/-
      2% per heartbeat; P<0.02), and multiple firing incidence of single units within a
      cardiac cycle (8 +/- 1 versus 4 +/- 1% per heartbeat; P<0.05) were substantially
      reduced at follow-up. BP, single-unit MSNA, and multi-unit MSNA remained
      unaltered in the non-RDN cohort at follow-up. RDN results in the substantial and
      rapid reduction in firing properties of single sympathetic vasoconstrictor
      fibers, this being more pronounced than multi-unit MSNA inhibition. Whether the
      earlier changes in single-unit firing patterns may predict long-term BP response
      to RDN warrants further exploration.

PMID- 23172928
TI  - Risk stratification by 24-hour ambulatory blood pressure and estimated glomerular
      filtration rate in 5322 subjects from 11 populations.
AB  - No previous study addressed whether in the general population estimated
      glomerular filtration rate (eGFR [Chronic Kidney Disease Epidemiology
      Collaboration formula]) adds to the prediction of cardiovascular outcome over and
      beyond ambulatory blood pressure. We recorded health outcomes in 5322 subjects
      (median age, 51.8 years; 43.1% women) randomly recruited from 11 populations, who
      had baseline measurements of 24-hour ambulatory blood pressure (ABP(24)) and
      eGFR. We computed hazard ratios using multivariable-adjusted Cox regression.
      Median follow-up was 9.3 years. In fully adjusted models, which included both
      ABP(24) and eGFR, ABP(24) predicted (P<=0.008) both total (513 deaths) and
      cardiovascular (206) mortality; eGFR only predicted cardiovascular mortality
      (P=0.012). Furthermore, ABP(24) predicted (P<=0.0056) fatal combined with
      nonfatal events as a result of all cardiovascular causes (555 events), cardiac
      disease (335 events), or stroke (218 events), whereas eGFR only predicted the
      composite cardiovascular end point and stroke (P<=0.035). The interaction terms
      between ABP(24) and eGFR were all nonsignificant (P>=0.082). For cardiovascular
      mortality, the composite cardiovascular end point, and stroke, ABP(24) added
      0.35%, 1.17%, and 1.00% to the risk already explained by cohort, sex, age, body
      mass index, smoking and drinking, previous cardiovascular disease, diabetes
      mellitus, and antihypertensive drug treatment. Adding eGFR explained an
      additional 0.13%, 0.09%, and 0.14%, respectively. Sensitivity analyses stratified
      for ethnicity, sex, and the presence of hypertension or chronic kidney disease
      (eGFR <60 mL/min per 1.73 m(2)) were confirmatory. In conclusion, in the general
      population, eGFR predicts fewer end points than ABP(24). Relative to ABP(24),
      eGFR is as an additive, not a multiplicative, risk factor and refines risk
      stratification 2- to 14-fold less.

PMID- 23172930
TI  - Absence of cardiotrophin 1 is associated with decreased age-dependent arterial
      stiffness and increased longevity in mice.
AB  - Cardiotrophin 1 (CT-1), an interleukin 6 family member, promotes fibrosis and
      arterial stiffness. We hypothesized that the absence of CT-1 influences arterial
      fibrosis and stiffness, senescence, and life span. In senescent 29-month-old
      mice, vascular function was analyzed by echotracking device. Arterial
      histomorphology, senescence, metabolic, inflammatory, and oxidative stress
      parameters were measured by immunohistochemistry, reverse transcription
      polymerase chain reaction, Western blot, and ELISA. Survival rate of wild-type
      and CT-1-null mice was studied. Vascular smooth muscle cells were treated with CT
      1 (10(-9) mol/L) for 15 days to analyze senescence. The wall stress-incremental
      elastic modulus curve of old CT-1-null mice was shifted rightward as compared
      with wild-type mice, indicating decreased arterial stiffness. Media thickness and
      wall fibrosis were lower in CT-1-null mice. CT-1-null mice showed decreased
      levels of inflammatory, apoptotic, and senescence pathways, whereas telomere
      linked proteins, DNA repair proteins, and antioxidant enzyme activities were
      increased. CT-1-null mice displayed a 5-month increased median longevity compared
      with wild-type mice. In vascular smooth muscle cells, chronic CT-1 stimulation
      upregulated apoptotic and senescence markers and downregulated telomere-linked
      proteins. The absence of CT-1 is associated with decreased arterial fibrosis,
      stiffness, and senescence and increased longevity in mice likely through
      downregulating apoptotic, senescence, and inflammatory pathways. CT-1 may be a
      major regulator of arterial stiffness with a major impact on the aging process.

PMID- 23172932
TI  - Ovarian cycle and sympathoexcitation in premenopausal women.
AB  - The influence of the ovarian cycle on muscle sympathetic nerve activity (MSNA)
      remains controversial. Some studies report an increase of resting MSNA during the
      mid luteal (ML) phase of the ovarian cycle compared with the early follicular
      phase, whereas other studies do not. These inconsistent findings may be
      attributable, in part, to the variable surges in estradiol and progesterone. We
      tested the hypothesis that the degree of sympathoexcitation during the ML phase
      (DeltaMSNA) is associated with changes in estradiol (DeltaE(2)) and progesterone
      (DeltaP). Multiple regression analysis of data from previous studies with
      complete recordings of mean arterial pressure, MSNA, E(2), and P during both
      early follicular and ML phases were available from 30 eumenorrheic women (age, 28
      +/- 1 years; body mass index, 23 +/- 0 kg/m(2)). ML phase increased E(2) (37 +/-
      2 to 117 +/- 9 pg/mL; P<0.001), P (1 +/- 0 to 11 +/- 1 ng/mL; P<0.001), and MSNA
      (12 +/- 1 to 15 +/- 1 bursts/min; P=0.02), but did not alter mean arterial
      pressure (83 +/- 2 to 83 +/- 2 mm Hg; P=0.91). DeltaMSNA was correlated with
      DeltaE(2) (r=-0.50, P=0.003) and DeltaE(2)/DeltaP (r=-0.52, P=0.002) but not
      DeltaP (r=0.21, P=0.13). There was no association between Deltamean arterial
      pressure and DeltaE(2) (r=-0.13, P=0.49), DeltaP (r=-0.04, P=0.83), or
      DeltaE(2)/DeltaP (r<0.01, P=0.98). In conclusion, sympathoexcitation during the
      ML phase of the ovarian cycle seems to be dependent, in part, on the degree of
      sex steroid surges. This dynamic interaction among E(2), P, and MSNA likely
      explains previously reported inconsistencies in the field; it remains possible
      that other sex steroids, such as testosterone, might explain further variance.

PMID- 23172931
TI  - A trial of 2 strategies to reduce nocturnal blood pressure in blacks with chronic
      kidney disease.
AB  - The objective of our study was to determine the effects of 2 antihypertensive
      drug dose schedules (PM dose and add-on dose) on nocturnal blood pressure (BP) in
      comparison with usual therapy (AM dose) in blacks with hypertensive chronic
      kidney disease and controlled office BP. In a 3-period, crossover trial, former
      participants of the African American Study of Kidney Disease were assigned to
      receive the following 3 regimens, each lasting 6 weeks, presented in random
      order: AM dose (once-daily antihypertensive medications taken in the morning), PM
      dose (once-daily antihypertensives taken at bedtime), and add-on dose (once-daily
      antihypertensives taken in the morning and an additional antihypertensive
      medication before bedtime [diltiazem 60-120 mg, hydralazine 25 mg, or additional
      ramipril 5 mg]). Ambulatory BP monitoring was performed at the end of each
      period. The primary outcome was nocturnal systolic BP. Mean age of the study
      population (n=147) was 65.4 years, 64% were men, and mean estimated glomerular
      filtration rate was 44.9 mL/min per 1.73 m(2). At the end of each period, mean
      (SE) nocturnal systolic BP was 125.6 (1.2) mm Hg in the AM dose, 123.9 (1.2) mm
      Hg in the PM dose, and 123.5 (1.2) mm Hg in the add-on dose. None of the pairwise
      differences in nocturnal, 24-hour, and daytime systolic BP was statistically
      significant. Among blacks with hypertensive chronic kidney disease, neither PM
      (bedtime) dosing of once-daily antihypertensive nor the addition of drugs taken
      at bedtime significantly reduced nocturnal BP compared with morning dosing of
      antihypertensive medications.

PMID- 23172933
TI  - Home blood pressure variability as cardiovascular risk factor in the population
      of Ohasama.
AB  - Blood pressure variability based on office measurement predicts outcome in
      selected patients. We explored whether novel indices of blood pressure
      variability derived from the self-measured home blood pressure predicted outcome
      in a general population. We monitored mortality and stroke in 2421 Ohasama
      residents (Iwate Prefecture, Japan). At enrollment (1988-1995), participants
      (mean age, 58.6 years; 60.9% women; 27.1% treated) measured their blood pressure
      at home, using an oscillometric device. In multivariable-adjusted Cox models, we
      assessed the independent predictive value of the within-subject mean systolic
      blood pressure (SBP) and corresponding variability as estimated by variability
      independent of the mean, difference between maximum and minimum blood pressure,
      and average real variability. Over 12.0 years (median), 412 participants died,
      139 of cardiovascular causes, and 223 had a stroke. In models including morning
      SBP, variability independent of the mean and average real variability (median, 26
      readings) predicted total and cardiovascular mortality in all of the participants
      (P<=0.044); variability independent of the mean predicted cardiovascular
      mortality in treated (P=0.014) but not in untreated (P=0.23) participants; and
      morning maximum and minimum blood pressure did not predict any end point
      (P>=0.085). In models already including evening SBP, only variability independent
      of the mean predicted cardiovascular mortality in all and in untreated
      participants (P<=0.046). The R(2) statistics, a measure for the incremental risk
      explained by adding blood pressure variability to models already including SBP
      and covariables, ranged from <0.01% to 0.88%. In a general population, new
      indices of blood pressure variability derived from home blood pressure did not
      incrementally predict outcome over and beyond mean SBP.

PMID- 23172934
TI  - Does white coat hypertension require treatment over age 80?: Results of the
      hypertension in the very elderly trial ambulatory blood pressure side project.
AB  - White coat hypertension is considered to be a benign condition that does not
      require antihypertensive treatment. Ambulatory blood pressure (ABP) was measured
      in 284 participants in the Hypertension in the Very Elderly Trial (HYVET), a
      double-blind randomized trial of indapamide sustained release 1.5 mg+/
      perindopril 2 to 4 mg versus matching placebo in hypertensive subjects (systolic
      blood pressure 160-199 mm Hg) aged >80 years. ABP recordings (Diasys Integra II)
      were obtained in 112 participants at baseline and 186 after an average follow-up
      of 13 months. At baseline, clinic blood pressure (CBP) exceeded the morning ABP
      by 32/10 mm Hg. Fifty percent of participants fulfilled the established criteria
      for white coat hypertension. The highest ABP readings were in the morning
      (average 140/80 mm Hg), the average night-time pressure was low at 124/72 mm Hg,
      and the average 24-hour blood pressure was 133/77 mm Hg. During follow-up, the
      systolic/diastolic blood pressure placebo-active differences averaged 6/5 mm Hg
      for morning ABP, 8/5 mm Hg for 24-hour ABP, and 13/5 mm Hg for CBP. The lowering
      of blood pressure over 24 hours supports the reduction in blood pressure with
      indapamide sustained release+/-perindopril as the explanation for the reduction
      in total mortality and cardiovascular events observed in the main HYVET study.
      Because we estimate that 50% had white coat hypertension in the main study, this
      condition may benefit from treatment in the very elderly.

PMID- 23172935
TI  - Team physician challenges in 2013: dealing with media and travelling across state
      borders.

PMID- 23172936
TI  - Flawed meta-analysis of a flawed literature: commentary on Versteeg et al.

PMID- 23172938
TI  - The UK's research excellence framework 2014.

PMID- 23172939
TI  - Survival after cardiac arrest in hospital improves in the US.

PMID- 23172937
TI  - Mast cell inhibition attenuates myocardial damage, adverse remodeling, and
      dysfunction during fulminant myocarditis in the rat.
AB  - BACKGROUND: Myocarditis is a life-threatening heart disease characterized by
      myocardial inflammation, necrosis, and chronic fibrosis. While mast cell
      inhibition has been suggested to prevent fibrosis in rat myocarditis, little is
      known about its effectiveness in attenuating cardiac remodeling and dysfunction
      in myocarditis. Thus, we sought to test the hypothesis that mast cell inhibition
      will attenuate the inflammatory reaction and associated left ventricular (LV)
      remodeling and dysfunction after fulminant autoimmune myocarditis.  Methods and
      RESULTS: To induce experimental autoimmune myocarditis, we immunized 30 rats with
      porcine cardiac myosin (PCM) twice at a 7-day interval. On day 8 animals were
      randomized into treatment with either an intraperitoneal (IP) injection of
      25mg/kg of cromolyn sodium (n = 13) or an equivalent volume (~0.5 mL IP) of
      normal saline (n = 11). All animals were scanned by serial echocardiography
      studies before treatment (baseline echocardiogram) and after 20 days of cromolyn
      sodium (28 days after immunization). Furthermore, serial cardiac magnetic
      resonance was performed in a subgroup of 12 animals. After 20 days of treatment
      (28 days from first immunization), hearts were harvested for histopathological
      analysis. By echocardiography, cromolyn sodium prevented LV dilatation and
      attenuated LV dysfunction, compared with controls. Postmortem analysis of hearts
      showed that cromolyn sodium reduced myocardial fibrosis, as well as the number
      and size of cardiac mast cells in the inflamed myocardium, compared with
      controls. CONCLUSIONS: Our study suggests that mast cell inhibition with cromolyn
      sodium attenuates adverse LV remodeling and dysfunction in myocarditis. This
      mechanism-based therapy is clinically relevant and could improve the outcome of
      patients at risk for inflammatory cardiomyopathy and heart failure.

PMID- 23172940
TI  - Mental health deteriorates in economically successful Taiwan.

PMID- 23172941
TI  - Job losses linked to myocardial infarction in US cohort.

PMID- 23172942
TI  - Increased incidence of hip fracture after first prescription for antihypertensive
      drugs.

PMID- 23172943
TI  - How good a doctor do you need to be?

PMID- 23172944
TI  - Falling through the gaps in care.

PMID- 23172945
TI  - UK doctors call on government to introduce minimum pricing for alcohol.

PMID- 23172946
TI  - Denmark cancels "fat tax" and shelves "sugar tax" because of threat of job
      losses.

PMID- 23172947
TI  - Alcohol, as well as sugary drinks, adds calories to the US diet, finds study.

PMID- 23172948
TI  - Foundation is laid for the "end of AIDS," says UN report.

PMID- 23172949
TI  - General practices will be inspected every two years, with 48 hours' notice in
      normal circumstances.

PMID- 23172950
TI  - Air pollution and type 2 diabetes: mechanistic insights.

PMID- 23172952
TI  - American Diabetes Association research symposium: diabetes and the brain.

PMID- 23172951
TI  - Clinical islet xenotransplantation: how close are we?

PMID- 23172953
TI  - The vascular contribution to insulin resistance: promise, proof, and pitfalls.

PMID- 23172954
TI  - New role for Grb10 signaling in the pancreas.

PMID- 23172955
TI  - The magnetic appeal of silencing theranostics.

PMID- 23172956
TI  - P-selectin glycoprotein ligand-1: a cellular link between perivascular adipose
      inflammation and endothelial dysfunction.

PMID- 23172957
TI  - Biomarkers that predict diabetic nephropathy: the long road from finding targets
      to clinical use.

PMID- 23172958
TI  - Longitudinal validation of hemoglobin A(1c) criteria for diabetes diagnosis: risk
      of retinopathy.

PMID- 23172959
TI  - The magic of mother's milk.

PMID- 23172960
TI  - Nicotine and insulin resistance: when the smoke clears.

PMID- 23172961
TI  - Ceramide and insulin resistance: how should the issue be approached?

PMID- 23172964
TI  - Comment on: Greenbaum et al. through the fog: recent clinical trials to preserve
      beta-cell function in type 1 diabetes. Diabetes 2012;61:1323-1330.

PMID- 23172966
TI  - Comment on: Visinoni et al. The role of liver fructose-1,6-bisphosphatase in
      regulating appetite and adiposity. Diabetes 2012;61:1122-1132.

PMID- 23172968
TI  - Comment on: Vila et al. B-type natriuretic peptide modulates ghrelin, hunger, and
      satiety in healthy men. Diabetes 2012;61:2592-2596.

PMID- 23172970
TI  - Reduction in carotid intima-media thickness after pancreatic islet
      transplantation in patients with type 1 diabetes.
AB  - OBJECTIVE: Determine the impact of islet transplantation on carotid intima-media
      thickness (CIMT), a marker for atherosclerosis, in type 1 diabetes without kidney
      disease. RESEARCH DESIGN AND METHODS: Consecutive case series of 15 adults (mean
      age [SD], 49 years [10 years]; 87% female) with type 1 diabetes for >=5 years
      (mean duration [SD], 30 years [12 years]; mean HbA(1c) [SD], 7.2% [0.9%]),
      without kidney disease, presenting with severe hypoglycemic unawareness to
      undergo allogeneic pancreatic islet transplant(s) (one to three each) in a phase
      1/2 and 3 clinical trial. Current follow-up ranges from 1 to 5 years (2005-2011).
      CIMT of the common and internal carotid arteries was measured before and every 12
      16 months after the first transplant (two to six CIMTs each) by one
      ultrasonographer and one blinded reader. CIMT was analyzed as change from
      baseline to 12- and 50-month follow-up; a combined CIMT score was calculated as
      the sum of the standardized IMT scores (SD units [SDs]) of both arteries.
      RESULTS: All patients achieved insulin independence after one to three
      transplants. CIMT decreased at 12 months (n = 15) for the common carotid (-0.058
      mm; P = 0.006) and combined score (-1.28 SDs; P = 0.004). In those with 50-month
      follow-up (n = 7), the decrease in the combined score continued from 12 (-1.59
      SDs; P = 0.04) to 50 months (-0.77 SDs; P = 0.04). During follow-up, the
      decreasing slope of change in CIMT was associated with decreasing slopes of
      change in HbA(1c), lipoproteins, and cardiovascular/inflammatory markers.
      CONCLUSIONS: Islet transplantation may ameliorate diabetes-related
      atherosclerosis through improved glycemic control consequent to restoring
      endogenous insulin secretion, and optimal lipid management posttransplant also
      contributes.

PMID- 23172971
TI  - Smoking is associated with reduced risk of autoimmune diabetes in adults
      contrasting with increased risk in overweight men with type 2 diabetes: a 22-year
      follow-up of the HUNT study.
AB  - OBJECTIVE: To investigate the association between smoking habits and risk of
      autoimmune diabetes in adults and of type 2 diabetes. RESEARCH DESIGN AND
      METHODS: We used data from the three surveys of the Nord-Trondelag Health Study,
      spanning 1984-2008 and including a cohort of 90,819 Norwegian men (48%) and women
      (52%) aged >=20 years. Incident cases of diabetes were identified by
      questionnaire and classified as type 2 diabetes (n = 1,860) and autoimmune
      diabetes (n = 140) based on antibodies to glutamic decarboxylase (GADA) and age
      at onset of diabetes. Hazard ratios (HRs) adjusted for confounders were estimated
      by Cox proportional hazards regression models. RESULTS: The risk of autoimmune
      diabetes was reduced by 48% (HR 0.52 [95% CI 0.30-0.89]) in current smokers and
      58% in heavy smokers (0.42 [0.18-0.98]). The reduced risk was positively
      associated with number of pack-years. Heavy smoking was associated with lower
      levels of GADA (P = 0.001) and higher levels of C-peptide (964 vs. 886 pmol/L; P
      = 0.03). In contrast, smoking was associated with an increased risk of type 2
      diabetes, restricted to overweight men (1.33 [1.10-1.61]). Attributable
      proportion due to an interaction between overweight and heavy smoking was
      estimated to 0.40 (95% CI 0.23-0.57). CONCLUSIONS: In this epidemiological study,
      smoking is associated with a reduced risk of autoimmune diabetes, possibly linked
      to an inhibitory effect on the autoimmune process. An increased risk of type 2
      diabetes was restricted to overweight men.

PMID- 23172972
TI  - Resistance versus aerobic exercise: acute effects on glycemia in type 1 diabetes.
AB  - OBJECTIVE: In type 1 diabetes, small studies have found that resistance exercise
      (weight lifting) reduces HbA(1c). In the current study, we examined the acute
      impacts of resistance exercise on glycemia during exercise and in the subsequent
      24 h compared with aerobic exercise and no exercise. RESEARCH DESIGN AND METHODS:
      Twelve physically active individuals with type 1 diabetes (HbA(1c) 7.1 +/- 1.0%)
      performed 45 min of resistance exercise (three sets of seven exercises at eight
      repetitions maximum), 45 min of aerobic exercise (running at 60% of Vo(2max)), or
      no exercise on separate days. Plasma glucose was measured during and for 60 min
      after exercise. Interstitial glucose was measured by continuous glucose
      monitoring 24 h before, during, and 24 h after exercise. RESULTS: Treatment-by
      time interactions (P < 0.001) were found for changes in plasma glucose during and
      after exercise. Plasma glucose decreased from 8.4 +/- 2.7 to 6.8 +/- 2.3 mmol/L
      (P = 0.008) during resistance exercise and from 9.2 +/- 3.4 to 5.8 +/- 2.0 mmol/L
      (P = 0.001) during aerobic exercise. No significant changes were seen during the
      no-exercise control session. During recovery, glucose levels did not change
      significantly after resistance exercise but increased by 2.2 +/- 0.6 mmol/L (P =
      0.023) after aerobic exercise. Mean interstitial glucose from 4.5 to 6.0 h
      postexercise was significantly lower after resistance exercise versus aerobic
      exercise. CONCLUSIONS: Resistance exercise causes less initial decline in blood
      glucose during the activity but is associated with more prolonged reductions in
      postexercise glycemia than aerobic exercise. This might account for HbA(1c)
      reductions found in studies of resistance exercise but not aerobic exercise in
      type 1 diabetes.

PMID- 23172973
TI  - Real-time improvement of continuous glucose monitoring accuracy: the smart sensor
      concept.
AB  - OBJECTIVE: Reliability of continuous glucose monitoring (CGM) sensors is key in
      several applications. In this work we demonstrate that real-time algorithms can
      render CGM sensors smarter by reducing their uncertainty and inaccuracy and
      improving their ability to alert for hypo- and hyperglycemic events. RESEARCH
      DESIGN AND METHODS: The smart CGM (sCGM) sensor concept consists of a commercial
      CGM sensor whose output enters three software modules, able to work in real time,
      for denoising, enhancement, and prediction. These three software modules were
      recently presented in the CGM literature, and here we apply them to the Dexcom
      SEVEN Plus continuous glucose monitor. We assessed the performance of the sCGM on
      data collected in two trials, each containing 12 patients with type 1 diabetes.
      RESULTS: The denoising module improves the smoothness of the CGM time series by
      an average of ~57%, the enhancement module reduces the mean absolute relative
      difference from 15.1 to 10.3%, increases by 12.6% the pairs of values falling in
      the A-zone of the Clarke error grid, and finally, the prediction module forecasts
      hypo- and hyperglycemic events an average of 14 min ahead of time. CONCLUSIONS:
      We have introduced and implemented the sCGM sensor concept. Analysis of data from
      24 patients demonstrates that incorporation of suitable real-time signal
      processing algorithms for denoising, enhancement, and prediction can
      significantly improve the performance of CGM applications. This can be of great
      clinical impact for hypo- and hyperglycemic alert generation as well in
      artificial pancreas devices.

PMID- 23172974
TI  - Sex differences in the association between serum ferritin and fasting glucose in
      type 2 diabetes among South Asian Surinamese, African Surinamese, and ethnic
      Dutch: the population-based SUNSET study.
AB  - OBJECTIVE: Moderately elevated iron stores below the levels commonly associated
      with hemochromatosis have been implicated in the etiology of diabetes. Studies
      suggest that iron status (measured by serum ferritin) differs significantly
      according to sex, but inconsistent findings have been reported. Our aim is to
      test the association between serum ferritin and the prevalence of type 2 diabetes
      and fasting glucose concentrations in a population-based, multiethnic, cross
      sectional study including men and women of African Surinamese, South Asian
      Surinamese, and ethnic Dutch origin. RESEARCH DESIGN AND METHODS: We analyzed
      data on 508 ethnic Dutch, 597 African Surinamese, and 339 South Asian Surinamese
      aged 35-60 years. Type 2 diabetes was defined as a fasting plasma glucose level
      >=7.0 mmol/L or a self-reported diagnosis. RESULTS: Serum ferritin was positively
      associated with type 2 diabetes and fasting glucose, but differences in the
      associations according to sex were observed. Serum ferritin concentration was
      positively associated with type 2 diabetes among women in all ethnic groups (odds
      ratio [OR] ethnic Dutch: 1.07 [95% CI 1.01-1.13]; OR South Asian Surinamese: 1.05
      [1.00-1.10]; OR African Surinamese: 1.05 [1.01-1.10]), but not among men. Serum
      ferritin was also more strongly associated with fasting glucose in women than in
      men. Moreover, the magnitude of sex differences in the association between serum
      ferritin and fasting glucose, but not type 2 diabetes, was more pronounced in the
      African Surinamese group than in the other ethnic groups (P for interaction
      <=0.0001). CONCLUSIONS: We found a positive association between serum ferritin
      and type 2 diabetes and fasting glucose in our multiethnic population, which
      appeared stronger among women than men. Further evaluation of the variation in
      sex differences between ethnic groups is warranted, particularly among the
      African Surinamese, to understand the mechanisms behind these sex differences.

PMID- 23172975
TI  - Heterogeneity of responses to real-time continuous glucose monitoring (RT-CGM) in
      patients with type 2 diabetes and its implications for application.
AB  - OBJECTIVE: To characterize glucose response patterns of people who wore a real
      time continuous glucose monitor (RT-CGM) as an intervention to improve glycemic
      control. Participants had type 2 diabetes, were not taking prandial insulin, and
      interpreted the RT-CGM data independently. RESEARCH DESIGN AND METHODS: Data were
      from the first 12 weeks of a 52-week, prospective, randomized trial comparing RT
      CGM (n = 50) with self-monitoring of blood glucose (n = 50). RT-CGM was used in 8
      of the first 12 weeks. A1C was collected at baseline and quarterly. This analysis
      included 45 participants who wore the RT-CGM >=4 weeks. Analyses examined the RT
      CGM data for common response patterns-a novel approach in this area of research.
      It then used multilevel models for longitudinal data, regression, and
      nonparametric methods to compare the patterns of A1C, mean glucose, glycemic
      variability, and views per day of the RT-CGM device. RESULTS: There were five
      patterns. For four patterns, mean glucose was lower than expected as of the first
      RT-CGM cycle of use given participants' baseline A1C. We named them favorable
      response but with high and variable glucose (n = 7); tight control (n = 14);
      worsening glycemia (n = 6); and incremental improvement (n = 11). The fifth was
      no response (n = 7). A1C, mean glucose, glycemic variability, and views per day
      differed across patterns at baseline and longitudinally. CONCLUSIONS: The
      patterns identified suggest that targeting people with higher starting A1Cs,
      using it short-term (e.g., 2 weeks), and monitoring for worsening glycemia that
      might be the result of burnout may be the best approach to using RT-CGM in people
      with type 2 diabetes not taking prandial insulin.

PMID- 23172976
TI  - White matter alteration in metabolic syndrome: diffusion tensor analysis.
AB  - OBJECTIVE: We explored the regional pattern of white matter alteration in
      subjects with metabolic syndrome. We also investigated whether white matter
      alteration was correlated with BMI. RESEARCH DESIGN AND METHODS: Seven middle
      aged men with metabolic syndrome and seven without metabolic syndrome underwent
      diffusion tensor imaging with a 3T magnetic resonance imaging imager. We analyzed
      the fractional anisotropy (FA) values by using a tract-based spatial statistics
      technique (whole-brain analysis). We subsequently focused on measuring the mean
      FA values of the right inferior fronto-occipital fasciculus (IFOF) of all
      subjects by tract-specific analysis (regional brain analysis). We used a Pearson
      correlation coefficient to evaluate the relationship between BMI and mean FA
      values of the right IFOF. RESULTS: In the whole-brain analysis, subjects with
      metabolic syndrome had significantly lower FA values than control subjects in
      part of the right external capsule (part of the right IFOF), the entire corpus
      callosum, and part of the deep white matter of the right frontal lobe. In the
      regional brain analysis, the mean FA value of the right IFOF was 0.41 +/- 0.03
      for subjects with metabolic syndrome and 0.44 +/- 0.05 for control subjects. A
      significant negative correlation was observed between BMI and FA values in the
      right IFOF (r = -0.56, P < 0.04). CONCLUSIONS: Our results show that
      microstructural white matter changes occur in patients with metabolic syndrome.
      FA values may be useful indices of white matter alterations in patients with
      metabolic syndrome.

PMID- 23172977
TI  - Systemic inflammation (C-reactive protein) in type 2 diabetic patients is
      associated with ambient air pollution in Pune City, India.
AB  - OBJECTIVE: To study the association between ambient air pollutants and serum C
      reactive protein (CRP) concentration in 1,392 type 2 diabetic patients in Pune,
      India. RESEARCH DESIGN AND METHODS: A cross-sectional study was conducted that
      linked daily time series of ambient air pollution data (obtained from central
      monitoring sites) and plasma CRP concentration in type 2 diabetic patients from
      the Wellcome Trust Genetic (WellGen) Study, recruited between March 2005 and May
      2007. Air pollution effects on CRP concentration were investigated with delays
      (lags) of 0-7 days and multiday averaging spans of 7, 14, and 30 days before
      blood collection adjusted for age, sex, BMI, hemoglobin, fasting plasma glucose,
      treatment with agents with anti-inflammatory action, season, air temperature, and
      relative humidity. RESULTS: Median CRP concentration was 3.49 mg/L. For 1 SD
      increase in SO(2) and oxides of nitrogen (NO(x)) concentrations in ambient air, a
      day before blood collection (lag(1)), we observed a significant increase in CRP
      (9.34 and 7.77%, respectively). The effect was higher with lag(2) (12.42% for
      SO(2) and 11.60% for NO(x)) and wore off progressively thereafter. We also found
      a significant association with multiday averaging times of up to 30 and 7 days
      for SO(2) and NO(x), respectively. No significant associations were found between
      particulate matter with an aerodynamic profile <=10 um (PM(10)) and CRP
      concentration except in summer. The association was significantly higher among
      patients with a shorter duration of diabetes, and in those not on statin and
      thiazolidinedione treatment. CONCLUSIONS: We demonstrate, for the first time, a
      possible contribution of ambient air pollution to systemic inflammation in Indian
      type 2 diabetic patients. This may have implications for vascular complications
      of diabetes.

PMID- 23172979
TI  - High School Classmates and College Success.
AB  - This paper uses administrative data from the University of Texas-Austin to
      examine whether the number of same high school classmates at college entry
      influences college achievement, measured by grade point average (GPA) and
      persistence. For each freshman cohort from 1993 through 2003 we calculate the
      number and ethnic makeup of college freshmen from each Texas high school.
      Empirical specifications include high school fixed effects to control for
      unobservable differences across schools that influence both college enrollment
      behavior and academic performance. Using an instrumental variables/fixed effects
      estimation strategy, we also evaluate whether "marginal" increases in the number
      of high school classmates influence college grades. Results show that students
      who arrive on campus with a larger number of high school classmates outperform
      their counterparts from smaller high school cohorts. Average effects of larger
      high school cohorts on college achievement are small, but a marginal increase in
      the number of same-race classmates raises GPA by 0.1 point. Results provide
      suggestive evidence that minority academic benefits from larger high school
      cohorts are greater for minority compared with white students.

PMID- 23172980
TI  - Synthetic Efforts Toward [3.3.1] Bridged Bicyclic Phloroglucinol Natural
      Products.

PMID- 23172981
TI  - Biosynthesis of Athmu, a alpha,gamma-hydroxy-beta-amino acid of pahayokolides A
      B.
AB  - Pahayokolides A-B are cyanobacteria derived non-ribosomal peptides which exhibit
      cytotoxicity against a number of cancer cell lines. The biosynthetic origin of
      the 3-amino-2,5,7,8-tetrahydroxy-10-methylundecanoic acid (Athmu) moiety has been
      investigated using stable isotope incorporation experiments. While alpha
      ketoisocaproic acid (alpha-KIC), alpha-hydroxyisocaproic acid (alpha-HIC) and
      leucine all serve as precursors to Athmu, the feeding of [1-(13)C] alpha-KIC
      results in more than threefold greater (13)C enrichment than the other
      precursors. This result suggests that alpha-KIC is the immediate precursor which
      is selected and activated by the adenylation domain of the loading NRPS module
      and subsequently reduced in a fashion similar to that of the recently identified
      pathways for cryptophycins A-B, cereulide and valinomycin.

PMID- 23172978
TI  - Variational multiscale models for charge transport.
AB  - This work presents a few variational multiscale models for charge transport in
      complex physical, chemical and biological systems and engineering devices, such
      as fuel cells, solar cells, battery cells, nanofluidics, transistors and ion
      channels. An essential ingredient of the present models, introduced in an earlier
      paper (Bulletin of Mathematical Biology, 72, 1562-1622, 2010), is the use of
      differential geometry theory of surfaces as a natural means to geometrically
      separate the macroscopic domain from the microscopic domain, meanwhile,
      dynamically couple discrete and continuum descriptions. Our main strategy is to
      construct the total energy functional of a charge transport system to encompass
      the polar and nonpolar free energies of solvation, and chemical potential related
      energy. By using the Euler-Lagrange variation, coupled Laplace-Beltrami and
      Poisson-Nernst-Planck (LB-PNP) equations are derived. The solution of the LB-PNP
      equations leads to the minimization of the total free energy, and explicit
      profiles of electrostatic potential and densities of charge species. To further
      reduce the computational complexity, the Boltzmann distribution obtained from the
      Poisson-Boltzmann (PB) equation is utilized to represent the densities of certain
      charge species so as to avoid the computationally expensive solution of some
      Nernst-Planck (NP) equations. Consequently, the coupled Laplace-Beltrami and
      Poisson-Boltzmann-Nernst-Planck (LB-PBNP) equations are proposed for charge
      transport in heterogeneous systems. A major emphasis of the present formulation
      is the consistency between equilibrium LB-PB theory and non-equilibrium LB-PNP
      theory at equilibrium. Another major emphasis is the capability of the reduced LB
      PBNP model to fully recover the prediction of the LB-PNP model at non-equilibrium
      settings. To account for the fluid impact on the charge transport, we derive
      coupled Laplace-Beltrami, Poisson-Nernst-Planck and Navier-Stokes equations from
      the variational principle for chemo-electro-fluid systems. A number of
      computational algorithms is developed to implement the proposed new variational
      multiscale models in an efficient manner. A set of ten protein molecules and a
      realistic ion channel, Gramicidin A, are employed to confirm the consistency and
      verify the capability. Extensive numerical experiment is designed to validate the
      proposed variational multiscale models. A good quantitative agreement between our
      model prediction and the experimental measurement of current-voltage curves is
      observed for the Gramicidin A channel transport. This paper also provides a brief
      review of the field.

PMID- 23172982
TI  - Union Formation Implications of Race and Gender Gaps in Educational Attainment:
      The Case of Latin America.
AB  - We use census microdata to assess the levels of educational homogamy in six Latin
      American countries: Argentina, Brazil, Chile, Costa Rica, Ecuador and Mexico.
      This paper contributes to the literature on homogamy in three ways. First, by
      conducting a comparative analysis between countries belonging to the still little
      studied region of Latin America, which is still undergoing intense and varied
      processes of demographic, economic, social, and political modernization. Second,
      by simultaneously including variables of structural and individual nature.
      Finally, by making progress with respect to the interactions between educational
      homogamy and other important variables associated with high levels of social
      inequality in the region: race, ethnicity and birthplace.

PMID- 23172984
TI  - ?
AB  - This article presents the experience acquired by participating in the
      international ethics of biomedical and psychosocial research training program of
      the Interdisciplinary Center for Studies on Bioethics of the University of Chile
      (2003-2004) and some reflections about the integration of knowledge acquired in
      my posterior work at scientific ethical review committees and ethics of research
      academic programs. Furthermore, in the elaboration of regulations for improving
      scientific and ethical review.

PMID- 23172983
TI  - GENE EXPRESSION PROFILING OF HUMAN LIVER CARCINOMA (HepG2) CELLS EXPOSED TO THE
      MARINE TOXIN OKADAIC ACID.
AB  - The marine toxin, okadaic acid (OA) is produced by dinoflagellates of the genera
      Prorocentrum and Dinophysis and is the causative agent of the syndrome known as
      diarrheic shellfish poisoning (DSP). In addition, OA acts as both a tumor
      promoter, attributed to OA-induced inhibition of protein phosphatases as well as
      an inducer of apoptosis. To better understand the potentially divergent
      toxicological profile of OA, the concentration dependent cytotoxicity and
      alterations in gene expression on the human liver tumor cell line HepG2 upon OA
      exposure were determined using RNA microarrays, DNA fragmentation, and cell
      proliferation assays as well as determinations of cell detachment and cell death
      in different concentrations of OA. mRNA expression was quantified for
      approximately 15,000 genes. Cell attachment and proliferation were both
      negatively correlated with OA concentration. Detached cells displayed necrotic
      DNA signatures but apoptosis also was broadly observed. Data suggest that OA has
      a concentration dependent effect on cell cycle, which might explain the divergent
      effects that at low concentration OA stimulates genes involved in the cell cycle
      and at high concentrations it stimulates apoptosis.

PMID- 23172985
TI  - Unraveling Uses and Effects of an Interactive Health Communication System.
AB  - By developing a number of measures distinguishing amount, type of content, and
      when and how that content is used, the current study revealed effective patterns
      of use that are associated with quality of life benefits during an eHealth
      intervention. Results generally suggest that the benefits depend on how a patient
      uses the system, far more than on sheer amount of exposure or even what type of
      content is chosen. The next generation of eHealth system should focus on
      providing new and varying content over time, but even more on encouraging
      intensity of use and long-term commitment to the system.

PMID- 23172986
TI  - Statistical Comparison of Carcinogenic Effects and Dose-Response Relationships in
      Rats and Mice for 2,4-Toluene Diamine to those Ascribed to Toluene Diisocyanate.
AB  - The U.S. National Toxicology Program (NTP) conducted 2-year bioassays of
      commercial grade toluene diisocyanate (TDI) (80% 2,4-TDI and 20% 2,6-TDI) and 2,4
      toluene diamine (TDA) and concluded that both were carcinogenic in rodents. In
      the TDI study, there was an unproven but likely formation of TDA either because
      of flawed test-substance handling and storage conditions and/or the atypical
      exposure conditions employed. Although the carcinogenic responses in both studies
      were qualitatively similar, several statistical analyses were performed to
      substantiate this possibility more rigorously. Seven different statistical
      approaches combine to yield a robust and consistent conclusion that, if only a
      small fraction (approximately 5%) of the dose of TDI were hydrolyzed to TDA in
      the TDI study, then that would be sufficient to explain the observed carcinogenic
      responses in the TDI study.

PMID- 23172987
TI  - Exploring the Determinants of the Perceived Risk of Food Allergies in Canada.
AB  - Food allergies are emerging health risks in much of the Western world, and some
      evidence suggests prevalence is increasing. Despite lacking scientific consensus
      around prevalence and management, policies and regulations are being implemented
      in public spaces (e.g., schools). These policies have been criticized as extreme
      in the literature, in the media, and by the non-allergic population. Backlash
      appears to be resulting from different perceptions of risk between different
      groups. This article uses a recently assembled national dataset (n = 3,666) to
      explore how Canadians perceive the risks of food allergy. Analyses revealed that
      almost 20% self-report having an allergic person in the household, while the
      average respondent estimated the prevalence of food allergies in Canada to be
      30%. Both of these measures overestimate the true clinically defined prevalence
      (7.5%), indicating an inflated public understanding of the risks of food
      allergies. Seventy percent reported food allergies to be substantial risks to the
      Canadian population. Multivariate logistic regression models revealed important
      determinants of risk perception including demographic, experience-based,
      attitudinal, and regional predictors. Results are discussed in terms of
      understanding emerging health risks in the post-industrial era, and implications
      for both policy and risk communication.

PMID- 23172988
TI  - Methacrylic-based nanogels for the pH-sensitive delivery of 5-fluorouracil in the
      colon.
AB  - Methacrylic-based copolymers in drug-delivery systems demonstrate a pH-sensitive
      drug-releasing behavior in the colon. In this study, copolymers of methacrylic
      acid and 2-ethyl hexyl acrylate were prepared using a microemulsion
      polymerization technique. The purified copolymer was characterized by Fourier
      transform infrared spectroscopy, proton nuclear magnetic resonance spectroscopy,
      and differential scanning calorimetry. 5-Fluorouracil (5-FU) was entrapped within
      methacrylic-based copolymers by a solvent evaporation method. The size of the
      nanogels formed was characterized by transmission electron microscopy and atomic
      force microscopy. In vitro drug-release studies using phosphate-buffered saline
      at different pH levels demonstrated the sustained release of 5-FU and its pH
      dependence. Cell proliferation assay of a human colon tumor colon cancer cell
      line (HCT-116) was performed and showed that the nanogels containing 5-FU
      exhibited considerable cytotoxicity in comparison with free 5-FU. Cell uptake of
      the nanogels was also monitored using confocal microscopy. Western blot analysis
      and flow cytometry studies confirmed that the nanogels could be successfully used
      as an efficient vector for pH-sensitive and controlled delivery of drugs
      specifically targeted to the colon.

PMID- 23172989
TI  - Treatment of prehypertension: lifestyle and/or medication.
AB  - Prehypertension is a warning to individuals with resting blood pressures between
      120/80 mmHg and 139/89 mmHg of an insidious progression of blood pressure towards
      hypertensive levels (>= 140/90 mmHg). Prehypertension is associated with
      increased cardiovascular risk and end organ damage compared with individuals who
      are normotensive. This review primarily focuses on internal and external factors
      associated with the prevalence of prehypertension. Elucidating all of the factors
      associated with a rise in resting blood pressure and comparing the effects of
      medication versus lifestyle changes may aid the clinician in developing a
      preventive and/or treatment strategy for each individual.

PMID- 23172990
TI  - The impact of tumor size change after target therapy on survival: analysis of
      patients enrolled onto three clinical trials of advanced NSCLC from one
      institution.
AB  - PURPOSE: To explore whether changes in tumor size impact survival in advanced non
      small-cell lung cancer (NSCLC) after target therapy, especially in patients with
      evaluation of stable disease (SD), and to review the applicability of the
      Response Evaluation Criteria in Solid Tumors (RECIST) criteria in target therapy.
      PATIENTS AND METHODS: Data from 88 NSCLC patients receiving gefitinib (250 mg,
      daily [qd]), erlotinib (150 mg, qd), and ZD6474 (100 mg, qd) in three clinical
      trials (IRESSA registration clinical trial, TRUST study, ZD6474 study) during
      November 2003 to June 2005 were retrospectively analyzed. The treatment effect
      (complete response, partial response, stable disease [SD], or progressive
      disease) was evaluated with radiologic assessment according to the RECIST
      criteria. SD patients were divided into two groups: SD-/0, in which the sum of
      the longest diameter of target lesions decreased by less than 30% or did not
      change; and SD+, in which the sum of the longest diameter of target lesions
      increased by less than 20%. The differences of progression-free survival (PFS)
      and overall survival (OS) between these groups were analyzed. RESULTS: In the
      whole group, 27 patients achieved complete response or partial response as best
      response, 40 achieved SD, and 22 had progressive disease. The median PFS and OS
      were 4 months and 11.1 months, respectively. In SD patients, 27 were SD-/0 and 13
      patients were SD+. The PFS and OS of SD+ patients was shorter than that of SD-/0
      patients (5.65 months vs 2.03 days, P < 0.001 and 12.2 months vs 7.1 months, P <
      0.001). CONCLUSION: The applicability of RECIST criteria was called into question
      in the evaluation of target therapy. Change in tumor size might predict survival
      in advanced NSCLC patients with target therapy and may be a surrogate endpoint
      for efficacy in target therapy.

PMID- 23172991
TI  - Pharmacological and clinical evidence of nevirapine immediate- and extended
      release formulations.
AB  - We reviewed the current information available on nevirapine immediate- and
      extended-release formulations and its role in single-dose and combination
      antiretroviral therapy. Nevirapine was approved in 1996 and was the first non
      nucleoside reverse-transcriptase inhibitor available for the treatment of HIV-1
      infection. Nevirapine has demonstrated good efficacy and a well-characterized
      safety profile. A major drawback is the low genetic barrier, allowing the
      emergence of resistance in the presence of single mutations in the reverse
      transcriptase gene. This shortcoming is particularly relevant when nevirapine is
      administered in a single dose to prevent mother-to-child transmission of HIV-1
      infection, compromising the efficacy of future non-nucleoside reverse
      transcriptase-inhibitor regimens. Studies published recently have probed the
      noninferiority of nevirapine compared to ritonavir-boosted atazanavir with both
      tenofovir disoproxil fumarate and emtricitabine in antiretroviral treatment-naive
      patients. In 2011, a new formulation of nevirapine (nevirapine extended release)
      that allowed once-daily dosing was approved by the Food and Drug Administration
      and by the European Medicines Agency. VERxVe, a study comparing nevirapine
      extended release with nevirapine immediate release in antiretroviral treatment
      naive patients, and TRANxITION, a study carried out in antiretroviral treatment
      experienced patients who switched therapy from nevirapine immediate release to
      nevirapine extended release, provided data on the noninferiority of the new
      formulation of nevirapine compared with nevirapine immediate release in terms of
      efficacy and safety. Nevirapine extended release will further increase the
      durability and persistence of nevirapine-containing antiretroviral therapy,
      allowing once-daily dosing regimens.

PMID- 23172992
TI  - Some characteristics of social interactions among adolescents in Croatia, Bosnia
      and Herzegovina, and Macedonia.
AB  - INTRODUCTION: The bioecological model refers to the basic social needs that a
      person has satisfied through social interactions. In individualist cultures, the
      need for independence is emphasized with the aim of self-realization and personal
      achievement. In collectivist cultures, togetherness is encouraged and it prevails
      over individuality. AIM: The aim of this study was to determine whether there
      were differences in adolescents (n = 1033) from three different cultural
      environments (Croatia, Bosnia and Herzegovina, and Macedonia) with regard to the
      various aspects of the social interactions and behaviors these adolescents
      exercise with their parents and friends. METHODS: THREE GROUPS OF QUESTIONNAIRES
      WERE USED: those that measure family interactions (the quality of family
      interactions, loneliness in the family, and family influence); those that assess
      peer interactions (quality of friendships, social loneliness, and influence of
      friendships); and those that examined behavioral variables (self-esteem,
      aggression, and prosocialness). RESULTS: Discriminant analysis has shown that
      there are two significant functions that differentiate subjects from the three
      different cultural environments. The first discriminant function that adequately
      discriminates between subjects in all three cultural environments is related to
      social and family loneliness and the influence of friends. Loneliness in the
      family, social loneliness, and influence of friends are most prevalent among
      adolescents in Macedonia and least among adolescents in Croatia. The second
      function that distinguished adolescents in Croatia from those in the other two
      cultural environments was primarily connected with the quality of family
      interactions, aggressiveness, parent influence, and self-esteem. Finally, it was
      found that adolescents from Bosnia and Herzegovina were more likely to engage in
      family interactions, have greater levels of parental influence, and appeared to
      be less aggressive and had lower self-esteem than adolescents from the other two
      regions.

PMID- 23172993
TI  - Brain Extracellular Space as a Diffusion Barrier.
AB  - The extracellular space (ECS) consists of the narrow channels between brain cells
      together with their geometrical configuration and contents. Despite being only 20
      60 nm in width, the ECS typically occupies 20% of the brain volume. Numerous
      experiments over the last 50 years have established that molecules moving through
      the ECS obey the laws of diffusion but with an effective diffusion coefficient
      reduced by a factor of about 2.6 compared to free diffusion. This review
      considers the origins of the diffusion barrier arising from the ECS and its
      properties. The paper presents a brief overview of software for implementing two
      point-source paradigms for measurements of localized diffusion properties: the
      real-time iontophoresis or pressure method for small ions and the integrative
      optical imaging method for macromolecules. Selected results are presented. This
      is followed by a discussion of the application of the MCell Monte Carlo
      simulation program to determining the importance of geometrical constraints,
      especially dead-space microdomains, and the possible role of interaction with the
      extracellular matrix. It is concluded that we can predict the impediment to
      diffusion of many molecules of practical importance and also use studies of the
      diffusion of selected molecular probes to reveal the barrier properties of the
      ECS.

PMID- 23172994
TI  - LHRH Agonists for the Treatment of Prostate Cancer: 2012.
AB  - The most recent guidelines on prostate cancer screening from the American
      Urological Association (2009), the National Comprehensive Cancer Network (2011),
      and the European Association of Urology (2011), as well as treatment and advances
      in disease monitoring, have increased the androgen deprivation therapy (ADT)
      population and the duration of ADT usage as the first-line treatment for
      metastatic prostate cancer. According to the European Association of Urology,
      gonadotropin-releasing hormone (GnRH) agonists have become the leading
      therapeutic option for ADT because they avoid the physical and psychological
      discomforts associated with orchiectomy. However, GnRH agonists display several
      shortcomings, including testosterone (T) surge ("clinical flare") and
      microsurges. T surge delays the intended serologic endpoint of T suppression and
      may exacerbate clinical symptoms. Furthermore, ADT manifests an adverse-event
      spectrum that can impact quality of life with its attendant well-documented
      morbidities. Strategies to improve ADT tolerability include a holistic management
      approach, improved diet and exercise, and more specific monitoring to detect and
      prevent T depletion toxicities. Intermittent ADT, which allows hormonal recovery
      between treatment periods, has become increasingly utilized as a methodology for
      improving quality of life while not diminishing chronic ADT efficacy, and may
      also provide healthcare cost savings. This review assesses the present and
      potential future role of GnRH agonists in prostate cancer and explores strategies
      to minimize the adverse-event profile for patients receiving ADT.

PMID- 23172995
TI  - Active surveillance for small renal masses.
AB  - Small renal masses (SRMs; <= 4 cm in dimension) have rapidly risen in incidence
      in recent decades and pose an increasingly common management dilemma in urology.
      SRMs are biologically heterogeneous and a wide variety of treatments exist with
      favorable oncologic outcomes. Active surveillance (AS) has emerged as a viable
      option for those not desiring surgery or those who are suboptimal candidates for
      surgery, with < 2% of patients progressing to metastatic disease in retrospective
      and prospective studies. This article reviews the current data regarding AS for
      SRM, operational considerations for an AS program, and criteria for safely
      selecting patients for this treatment strategy.

PMID- 23172997
TI  - Innovation in Endourology and Minimally Invasive Surgery: Highlights From the
      29th World Congress of Endourology and SWL 2011, November 30-December 3, 2011,
      Kyoto, Japan.

PMID- 23172996
TI  - Radical retropubic prostatectomy: comparison of the open and robotic approaches
      for treatment of prostate cancer.
AB  - Radical prostatectomy represents the standard of care for surgical treatment of
      clinically localized prostate cancer. First described in 1904, the operation
      became widely performed only after advances in diagnostic and surgical techniques
      occurred later in the century. Over time, open retropubic radical prostatectomy
      (RRP) became the most common operation for prostate cancer, and excellent long
      term survival outcomes have been reported. More recently, minimally invasive
      techniques such as the robotic-assisted laparoscopic radical prostatectomy
      (RALRP) were introduced. Despite a lack of prospectively collected, long-term
      data supporting its use, RALRP has overtaken RRP as the most frequently performed
      prostate cancer operation in the United States. This article uses currently
      available data to compare oncologic, functional, and quality-of-life outcomes
      associated with both the open and robotic approaches to radical prostatectomy.

PMID- 23172998
TI  - Adult Wilms' tumor with a unique presentation of high-grade Fever, photophobia,
      and headache.
AB  - Wilms' tumor is the second most common tumor in children, accounting for 6% to 7%
      of all childhood tumors. However, in adults, it is a rare occurrence. The true
      incidence of adult Wilms' tumor is difficult to ascertain because of its rarity
      in the adult population. A review of literature demonstrates that fewer than 300
      cases have been reported worldwide. Treatment guidelines in adults have not been
      established, although reported prognosis is worse for adults compared with
      children because the disease is more advanced in adults at the time of diagnosis.
      Reported here is a case of adult Wilms' tumor presenting as high-grade fever and
      abnormal laboratory values.

PMID- 23172999
TI  - Pelvic surgeons caught in the meshes of the law.

PMID- 23173000
TI  - Urodynamics in children.

PMID- 23173001
TI  - Congenital bladder abnormalities.

PMID- 23173004
TI  - One-Step Hydrothermal Synthesis of Comb-Like ZnO Nanostructures.
AB  - Zinc Oxide (ZnO) nano-superstructures (NSSs) have attracted intense research
      interests due to their large surface areas and unique properties. In this work,
      we report an original approach to synthesize ZnO NSSs in a one-step manner with a
      hydrothermal method. The crystalline structures and growth mechanism can be
      understood by surface energy calculations. The reaction kinetics was investigated
      for the control of the morphology of ZnO NSSs. The critical role of the
      morphology of Au catalysts in the synthesis of ZnO nanostructures has been
      demonstrated. Such ZnO NSSs can be fabricated on various rigid and flexible
      substrates for applications in electronics, solar cells and piezoelectric
      devices.

PMID- 23173006
TI  - Plan B for stimulating stem cell division.

PMID- 23173005
TI  - Cooperativity of Rb, Brca1, and p53 in malignant breast cancer evolution.
AB  - Breast cancers that are "triple-negative" for the clinical markers ESR1, PGR, and
      HER2 typically belong to the Basal-like molecular subtype. Defective Rb, p53, and
      Brca1 pathways are each associated with triple-negative and Basal-like subtypes.
      Our mouse genetic studies demonstrate that the combined inactivation of Rb and
      p53 pathways is sufficient to suppress the physiological cell death of mammary
      involution. Furthermore, concomitant inactivation of all three pathways in
      mammary epithelium has an additive effect on tumor latency and predisposes highly
      penetrant, metastatic adenocarcinomas. The tumors are poorly differentiated and
      have histologic features that are common among human Brca1-mutated tumors,
      including heterogeneous morphology, metaplasia, and necrosis. Gene expression
      analyses demonstrate that the tumors share attributes of both Basal-like and
      Claudin-low signatures, two molecular subtypes encompassed by the broader, triple
      negative class defined by clinical markers.

PMID- 23173007
TI  - Genomic medicine: evolving science, evolving ethics.
AB  - Genomic medicine is rapidly evolving. Next-generation sequencing is changing the
      diagnostic paradigm by allowing genetic testing to be carried out more quickly,
      less expensively and with much higher resolution; pushing the envelope on
      existing moral norms and legal regulations. Early experience with implementation
      of next-generation sequencing to diagnose rare genetic conditions in symptomatic
      children suggests ways that genomic medicine might come to be used and some of
      the ethical issues that arise, impacting test design, patient selection, consent,
      sequencing analysis and communication of results. The ethical issues that arise
      from use of new technologies cannot be satisfactorily analyzed until they are
      understood and they cannot be understood until the technologies are deployed in
      the real world.

PMID- 23173008
TI  - Self-perceived strengths among people who are homeless.
AB  - This study examined self-perceived strengths among 116 people who were homeless.
      Those who had experienced a longer period of current homelessness tended to
      report fewer personal strengths (r = -0.23). Nonetheless, in spite of their
      marginalized position in society, the vast majority of participants (114 out of
      116) perceived personal strengths. A prior diagnosis with mental illness was not
      associated with the number of strengths reported, but self-perception of
      strengths was associated with altruistic orientation. The Values in Action (VIA)
      taxonomy of character strengths captured many of the responses generated by this
      population. The most frequently mentioned character categories included social
      intelligence, kindness, persistence, authenticity and humour. The most frequently
      mentioned other strengths included personal skills (e.g. music, sports), job
      skills, intelligence and education. The results have relevance for efforts to
      build self-perceptions that facilitate escape from homelessness.

PMID- 23173009
TI  - Impact of sterol tilt on membrane bending rigidity in cholesterol and 7DHC
      containing DMPC membranes.
AB  - Cholesterol is so essential to the proper function of mammalian cell membranes
      that even strikingly small inborn errors in cholesterol synthesis can be
      devastating. Here we combine molecular dynamics simulations with small angle x
      ray diffraction experiments to compare mixed sterol/DMPC membranes over a wide
      range of sterol compositions for two types of sterols: cholesterol and its
      immediate metabolic precursor 7DHC, that differs from cholesterol by one double
      bond. We find that while most membrane properties are only slightly affected by
      the replacement of one sterol by the other, the tilt degree of freedom, as gauged
      by the tilt modulus, is significantly larger for cholesterol than for 7DHC over a
      large range of concentrations. In silico mutations of one sterol into the other
      further support these findings. Moreover, bending rigidities calculated from
      simulations and estimated in experiments show that cholesterol stiffens membranes
      to a larger extent than 7DHC. We discuss the possible mechanistic link between
      sterol tilt and the way it impacts the membrane mechanical properties, and
      comment on how this link may shed light on the way replacement of cholesterol by
      7DHC leads to disease.

PMID- 23173010
TI  - Resource Group Assertive Community Treatment (RACT) as a Tool of Empowerment for
      Clients with Severe Mental Illness: A Meta-Analysis.
AB  - The aim of the current meta-analysis was to explore the effectiveness of the
      method here labeled Resource Group Assertive Community Treatment (RACT) for
      clients with psychiatric diagnoses as compared to standard care during the period
      2001 - 2011. Included in the meta-analysis were 17 studies comprising a total of
      2263 clients, 1291 men and 972 women, with a weighted mean age of 45.44 years.
      The diagnoses of 86 % of the clients were within the psychotic spectrum while 14
      % had other psychiatric diagnoses. There were six randomized controlled trials
      and eleven observational studies. The studies spanned between 12 and 60 months,
      and 10 of them lasted 24 months. The results indicated a large effect-size for
      the "grand total measure" (Cohen's d = 0.80). The study comprised three outcome
      variables: Symptoms, Functioning, and Well-being. With regard to Symptoms, a
      medium effect for both randomized controlled trials and non-randomized studies
      was found, whereas Functioning showed large effects for both types of design.
      Concerning Well-being both large and medium effects were evident. The conclusions
      of the meta-analysis were that the treatment of clients with Resource Group
      Assertive Community Treatment yields positive effects for clients with psychoses
      and that the method may be of use for clients within the entire psychiatric
      spectrum.

PMID- 23173011
TI  - Counseling in primary care improves depression and quality of life.
AB  - INTRODUCTION: To measure the effectiveness on Quality of Life of adjunctive
      cognitive behavioral counseling in the setting of General Practitioners (GPs)
      along with the treatment as usual (TAU;) for the treatment of depression.
      METHODS: Six month-controlled trial of patients who were referred to randomly
      assigned GPs (four for experimental group of patients and ten for the control)
      was done. Experimental sample had 34 patients with DSM-IV diagnosis of Depression
      (Depressed Episode, Dysthymia, or Adjustment Disorder with Depressed Mood)
      receiving the TAU supplemented with counseling. Control group had 30 patients
      with diagnosis of Depression receiving only the TAU. RESULTS: The Beck Depression
      Inventory (BDI) score improved in both groups. Patients in the experimental group
      showed greater improvement compared to the control group at T2. The World Health
      Organization Quality OF Life Questionnaire (WHOQOL) score also improved in the
      experimental group but not in the control group. The improvement in the
      experimental group was statistically significant in terms of both BDI and WHOQOL
      scores. CONCLUSIONS: Adding counseling to TAU in general medical practice
      settings is more effective in controlling the symptoms of depression and
      improving the quality of life as measured over a period of six months, than TAU
      alone. These results while encouraging, also calls for a larger study involving a
      largersample size and a longer period of time.

PMID- 23173012
TI  - Broadening of Generalized Anxiety Disorders Definition Does not Affect the
      Response to Psychiatric Care: Findings from the Observational ADAN Study.
AB  - OBJECTIVE: To elucidate the consequences of broadening DSM-IV criteria for
      generalized anxiety disorder (GAD), we examined prospectively the evolution of
      GAD symptoms in two groups of patients; one group diagnosed according to DSM-IV
      criteria and the other, according to broader criteria. METHOD: Multicentre,
      prospective and observational study conducted on outpatient psychiatric clinics.
      Patients were selected from October 2007 to January 2009 and diagnosed with GAD
      according to DSM-IV criteria (DSM-IV group) or broader criteria. Broader criteria
      were considered 1-month of excessive or non-excessive worry and only 2 of the
      associated symptoms listed on DSM-IV for GAD diagnosis. Socio-demographic data,
      medical history and functional outcome measures were collected three times during
      a 6-month period. RESULTS: 3,549 patients were systematically recruited; 1,815
      patients in DSM-IV group (DG) and 1,264 in broad group (BG); 453 patients did not
      fulfil inclusion criteria and were excluded. Most patients (87.9% in DG, 82.0% in
      BG) were currently following pharmacological therapies (mainly benzodiazepines)
      to manage their anxiety symptoms. The changes observed during the study were:
      49.0% and 58.0%, respectively of patients without anxiety symptoms as per HAM-A
      scale at the 6 month visit (p=0.261) and 59.7% and 67.7%, respectively (p=0.103)
      of responder rates (> 50% reduction of baseline scoring). CONCLUSION: Broadening
      of GAD criteria does not seem to affect psychiatric care results in subjects with
      GAD, is able to identify the core symptoms of the disease according to the DSM-IV
      criteria and could lead to an earlier diagnosis.

PMID- 23173013
TI  - Predicting the survival time for diffuse large B-cell lymphoma using microarray
      data.
AB  - The present study was conducted to predict survival time in patients with diffuse
      large B-cell lymphoma, DLBCL, based on microarray data using Cox regression model
      combined with seven dimension reduction methods. This historical cohort included
      2042 gene expression measurements from 40 patients with DLBCL. In order to
      predict survival, a combination of Cox regression model was used with seven
      methods for dimension reduction or shrinkage including univariate selection,
      forward stepwise selection, principal component regression, supervised principal
      component regression, partial least squares regression, ridge regression and
      Losso. The capacity of predictions was examined by three different criteria
      including log rank test, prognostic index and deviance. MATLAB r2008a and RKWard
      software were used for data analysis. Based on our findings, performance of ridge
      regression was better than other methods. Based on ridge regression coefficients
      and a given cut point value, 16 genes were selected. By using forward stepwise
      selection method in Cox regression model, it was indicated that the expression of
      genes GENE3555X and GENE3807X decreased the survival time (P=0.008 and P=0.003,
      respectively), whereas the genes GENE3228X and GENE1551X increased survival time
      (P=0.002 and P<0.001, respectively). This study indicated that ridge regression
      method had higher capacity than other dimension reduction methods for the
      prediction of survival time in patients with DLBCL. Furthermore, a combination of
      statistical methods and microarray data could help to detect influential genes in
      survival.

PMID- 23173014
TI  - Admission cardiotocography: Its role in predicting foetal outcome in high-risk
      obstetric patients.
AB  - BACKGROUND: Routine and continuous electronic monitoring of foetal heart rate
      (FHR) in labour has become an established obstetric practice in high-risk
      pregnancies in industrialised countries. However, the same may not be possible in
      non-industrialised countries where antenatal care is inadequate with a large
      number of high-risk pregnancies being delivered in crowded settings and
      inadequate health care provider to patient ratios. AIMS: The objective of this
      study was to evaluate the predictive value of the admission cardiotocogram (CTG)
      in detecting foetal hypoxia at the time of admission in labour and to correlate
      the results of the admission CTG with the perinatal outcome in high-risk
      obstetric cases. METHOD: This was a prospective observational study conducted in
      the labour and maternity ward of a hospital in Gangtok, India, during the period
      2008 to 2010. The study included high-risk pregnant women, admitted via the
      emergency or outpatient department with a period of gestation >=36 weeks, in
      first stage of labour with foetus in the cephalic presentation. All women were
      subjected to an admission CTG, which included a 20 minute recording of FHR and
      uterine contractions. RESULTS: One hundred and sixty patients were recruited. The
      majority of women were primigravida in the 21-30 years age group. About 42%
      patients were postdated pregnancy followed by pregnancy-induced hypertension
      (PIH) (15.6%) and premature rupture of membranes (PROM) (11.3%) as the major risk
      factors. The admission CTG were 'reactive' in 77%, 'equivocal' in 14.4% and
      'ominous' in 8.7% women. Incidence of foetal distress, moderate-thick meconium
      stained liquor and neonatal intensive care unit (NICU) admission was
      significantly more frequent among patients with ominous test results compared
      with equivocal or reactive test results on admission. Incidence of vaginal
      delivery was more common when the test was reactive. CONCLUSION: The admission
      CTG appears to be a simple non-invasive test that can serve as a screening tool
      in 'triaging' foetuses of high-risk obstetric patients in non-industrialised
      countries with a heavy workload and limited resources.

PMID- 23173015
TI  - Carotid stenting in a nonagenarian patient with symptomatic carotid stenosis.
AB  - Carotid artery stenosis is a disabling disease in all age groups. Elderly people
      are more prone to recurrent strokes due to advancing age and multiple co
      morbidities. Treatment options for symptomatic carotid stenosis in the very
      elderly are the same as in younger patients although with a higher operative
      risk. We describe a successful case of carotid artery stenting in a nonagenarian
      with symptomatic carotid artery stenosis, a subgroup for whom treatment options
      are rarely discussed in guidelines.

PMID- 23173016
TI  - Community acquired bilateral upper lobe pneumonia with acute adrenal
      insufficiency: A new face of Achromobacter Xylosoxidans.
AB  - Achromobacter xylosoxidans is an uncommon pathogen of low virulence known to
      cause serious nosocomial infection in the immunocompromised. Its inherent multi
      drug resistance makes treatment difficult. Community-acquired infections are rare
      despite its ubiquitous existence. We present a 50-year-old immunocompetent woman
      who presented with one-month history of coughing with expectoration who was
      subsequently diagnosed with bilateral upper lobe pneumonia and acute adrenal
      insufficiency. Achromobacter xylosoxidans was isolated from sputum and
      bronchoalveolar lavage culture. The acute adrenal insufficiency recovered after
      appropriate antibiotic therapy. Amongst the myriad of presentations, we highlight
      the rarity of acute adrenal insufficiency triggered by the infection.

PMID- 23173017
TI  - Surgeons' adherence to guidelines for surgical antimicrobial prophylaxis - a
      review.
AB  - Surgical site infections are the most common nosocomial infection among surgical
      patients. Patients who experience surgical site infections are associated with
      prolonged hospital stay, rehospitalisation, increased morbidity and mortality,
      and costs. Consequently, surgical antimicrobial prophylaxis (SAP), which is a
      very brief course of antibiotic given just before the surgery, has been
      introduced to prevent the occurrence of surgical site infections. The efficacy of
      SAP depends on several factors, including selection of appropriate antibiotic,
      timing of administration, dosage, duration of prophylaxis and route of
      administration. In many institutions around the globe, evidence-based guidelines
      have been developed to advance the proper use of SAP. This paper aims to review
      the studies on surgeons' adherence to SAP guidelines and factors influencing
      their adherence. A wide variation of overall compliance towards SAP guidelines
      was noted, ranging from 0% to 71.9%. The misuses of prophylactic antibiotics are
      commonly seen, particularly inappropriate choice and prolonged duration of
      administration. Lack of awareness of the available SAP guidelines, influence of
      initial training, personal preference and influence from colleagues were among
      the factors which hindered the surgeons' adherence to SAP guidelines. Immediate
      actions are needed to improve the adherence rate as inappropriate use of SAP can
      lead to the emergence of a strain of resistant bacteria resulting in a number of
      costs to the healthcare system. Corrective measures to improve SAP adherence
      include development of guidelines, education and effective dissemination of
      guidelines to targeted surgeons and routine audit of antibiotic utilisation by a
      dedicated infection control team.

PMID- 23173018
TI  - An unusual cause for recurrent jaundice in an otherwise healthy male.
AB  - A 41-year-old Asian-Indian male presented with recurrent episodes of jaundice
      over the past six months. Physical examination was normal, barring mild icterus.
      Laboratory parameters revealed indirect hyperbilirubinemia. Further evaluation
      yielded a diagnosis of severe nutritional vitamin B12 deficiency. Indirect
      hyperbilirubinemia was ascribed to ineffective erythropoiesis. Underlying
      Gilbert's syndrome was ruled out by provocative testing with lipid-restricted
      diet. Presentation of severe vitamin B12 deficiency with isolated
      hyperbilirubinemia without concomitant major haematologic or neurologic
      dysfunction is unusual and potentially underdiagnosed. Awareness of this
      possibility can permit early diagnosis of vitamin B12 deficiency and forestall
      development of severe haematologic and neurologic sequelae.

PMID- 23173019
TI  - Hospital discharge information after elective total hip or knee joint replacement
      surgery: A clinical audit of preferences among general practitioners.
AB  - The demand for elective joint replacement (EJR) surgery for degenerative joint
      disease continues to rise in Australia, and relative to earlier practices,
      patients are discharged back to the care of their general practitioner (GP) and
      other community-based providers after a shorter hospital stay and potentially
      greater post-operative acuity. In order to coordinate safe and effective post
      operative care, GPs rely on accurate, timely and clinically-informative
      information from hospitals when their patients are discharged. The aim of this
      project was to undertake an audit with GPs regarding their preferences about the
      components of information provided in discharge summaries for patients undergoing
      EJR surgery for the hip or knee.GPs in a defined catchment area were invited to
      respond to an online audit instrument, developed by an interdisciplinary group of
      clinicians with knowledge of orthopaedic surgery practices. The 15-item
      instrument required respondents to rank the importance of components of discharge
      information developed by the clinician working group, using a three-point rating
      scale.Fifty-three GPs and nine GP registrars responded to the audit invitation
      (11.0% response rate). All discharge information options were ranked as
      'essential' by a proportion of respondents, ranging from 14.8-88.5%. Essential
      information requested by the respondents included early post-operative actions
      required by the GP, medications prescribed, post-operative complications
      encountered and noting of any allergies. Non-essential information related to the
      prosthesis used. The provision of clinical guidelines was largely rated as
      'useful' information (47.5-56.7%).GPs require a range of clinical information to
      safely and effectively care for their patients after discharge from hospital for
      EJR surgery. Implementation of changes to processes used to create discharge
      summaries will require engagement and collaboration between clinical staff,
      hospital administrators and information technology staff, supported in parallel
      by education provided to junior medical staff.

PMID- 23173020
TI  - Experiences in the implementation of a national policy: A retrospective analysis
      of the Australian Chronic Dental Disease Scheme.
AB  - BACKGROUND: The Chronic Dental Disease Scheme (CDSS) is the first public dental
      policy in Australia to attract Medicare benefits for dental services. AIMS: This
      study examines the utilisation of a new federal method of funding dental care in
      Australia and provides an insight into the implications of government dental
      programs. The program titled; Chronic Dental Disease Scheme, provided government
      subsidised dental care for people suffering from a chronic medical condition.
      METHOD: A retrospective analysis of activity data using the relevant item numbers
      were extracted from the open source Medicare Benefits Schedule database (MBS) for
      years 2007-2009. RESULTS: During the study period, a total of approximately five
      million dental services were provided. There was a disproportionate use of
      services between jurisdictions. The highest proportion (66%) of services was
      provided in the state of New South Wales (NSW) with Victoria second (22%). The
      adjusted value of care provided as a proportion of comprehensive examinations
      ranged from $1937 in the northern territory (NT) to $2900 in NSW. The value of
      care per dentist ranged from nearly $80 000 down to less than $1000 and the value
      of care per adult of the population ranged between $53 and $1 across Australia.
      The highest was always in NSW and the lowest always being the NT. Fixed
      prosthodontics (reconstruction) accounted for the significant costs associated
      with the program. CONCLUSION: The scheme has been utilised above its budget
      estimate with prosthodontics accounting for the majority of expenses. Treatment
      plans differed between jurisdictions. The increase in utilisation of the scheme
      was coincident with periods of increased in subsidy and remuneration and has been
      postulated to be a main driver for its utilisation rather than the improvement in
      chronic health.

PMID- 23173021
TI  - A six-minute video-clip to ponder the values fostered by health technology.
AB  - As part of our research team's knowledge transfer and exchange (KTE) initiatives,
      we developed a six-minute video-clip to enable productive deliberations among
      technology developers, clinicians and patient representatives. This video-clip
      summarises in plain language the valuable goals and features that are embedded in
      health technology and raises questions regarding the direction that should be
      taken by health care innovations. The use of such video-clips creates unique
      opportunities for face-to-face deliberations by enabling participants to interact
      and debate policy issues that are pivotal to the sustainability of health care
      systems. In our experience, we found that audiovisual-elicitation-based KTE
      initiatives can fill an important communication gap among key stakeholders:
      pondering, from a health care system perspective, why and how certain kinds of
      medical technologies bring a more valuable response to health care needs when
      compared to others.

PMID- 23173022
TI  - Identification of G-Quadruplex Inducers Usinga Simple, Inexpensiveand Rapid High
      Throughput Assay, and TheirInhibition of Human Telomerase.
AB  - Telomeres are protein and DNA complexes located atchromosome ends. Telomeric DNA
      is composed of a double stranded region of repetitive DNA followed by single
      stranded 3' extension of aG-rich sequence. Single-stranded G-rich sequencescan
      fold into G-quadruplex structures,and molecules that stabilize G-quadruplexes are
      known to inhibit the enzyme telomerase and disrupt telomere maintenance. Because
      telomere maintenance is required for proliferation of cancer cells, G-quadruplex
      stabilizers have become attractive prospects for anticancer drug
      discovery.However, telomere-targeting G-quadruplex ligands have yet to enter the
      clinic owing in part to poor pharmacokinetics and target selectivity. Increasing
      the pharmacophore diversity of G-quadruplex and specifically telomeric-DNA
      targeting agents should assist in overcoming these shortcomings. In this work, we
      report the identification and validation ofligands that bind telomeric DNA and
      induce G-quadruplex formationusing the NCI Diversity Set I, providing validation
      of anextremely simple, rapid and high-throughput screen using FRET technology.
      Hits from the screen were validated by examining telomerase inhibition and G
      quadruplex inductionusing CD spectroscopy and DNA polymerase stop assays. We show
      that two known DNA binding molecules, ellipticine derivativeNSC 176327
      (apyridocarbazole) and NSC 305831 (an antiparasitic hetero-cyclediamidine
      referred to as furamidine and DB75),are selective induceG-quadruplex formation in
      the human telomeric sequence and bind telomeric DNA quadruplexes in the absence
      of stabilizing monovalent cations with molar ratios(molecule: DNA)of 4:1and
      1.5:1, respectively.

PMID- 23173023
TI  - Evaluation of immunoprotective activity of six leptospiral proteins in the
      hamster model of leptospirosis.
AB  - Leptospirosis is a worldwide zoonosis caused by pathogenic Leptospira. The whole
      genome sequence of L. interrogans serovar Copenhageni together with
      bioinformatics tools represent a great opportunity to search for novel antigen
      candidates that could be used as subunit vaccine against leptospirosis. We
      focused on six genes encoding for conserved hypothetical proteins predicted to be
      exported to the outer membrane. The genes were amplified by PCR from Leptospira
      interrogans genomic DNA and were cloned and expressed in Escherichia coli. The
      recombinant proteins tagged with N-terminal hexahistidine were purified by metal
      charged chromatography. The immunization of hamsters followed by challenge with
      lethal dose of virulent strain of Leptospira showed that the recombinant proteins
      Lsa21, Lsa66 and rLIC11030 elicited partial protection to animals. These proteins
      could be used combined or in a mixture with novel adjuvants in order to improve
      their effectiveness.

PMID- 23173024
TI  - Intramedullary fixation of diaphyseal clavicle fractures using the rockwood
      clavicle pin: review of 86 cases.
AB  - AIM: This study reports the safety, efficacy and functional and patient centred
      outcomes of the largest published series of patients treated with the Rockwood
      clavicle pin (intramedullary device) to date. PATIENTS AND METHODS: A
      retrospective review of case notes, radiographs and follow-up by questionnaire
      was conducted. 86 patients were operated upon, 70 for acute fractures (group A)
      and 16 for non-union (group B). RESULTS: Rate of non-union was 2 (2.9%) in group
      A and 0 in group B. Mean Disability of the Arm, Shoulder and Hand (DASH) scores
      were 5.9 for group A and 8.7 for group B. Satisfaction was rated as good or
      excellent in 61 (96.8%) of responders and all patients would have the procedure
      again. Pin prominence was the predominant complication in both groups and all
      patients underwent a second procedure for metalwork removal. DISCUSSION: Rockwood
      clavicle pins are as effective as plates in achieving union and maintaining
      length, however the advantages of this less invasive technique should be weighed
      against the common complication of pin prominence and the inconvenience of
      removal of metalwork in all cases.

PMID- 23173025
TI  - HIV/AIDS-Related Knowledge and Behaviors Among Most-at-Risk Populations in
      Vietnam.
AB  - The U.S. President's Emergency Plan for AIDS Relief (PEPFAR) has supported the
      Vietnamese Ministry of Health (MOH) in implementing behavior change strategies to
      slow the HIV epidemic. These programs target commercial sex workers (CSW),
      injection drug users (IDU), and men who have sex with men (MSM). Using data from
      a program evaluation to assess effectiveness of the PEPFAR intervention, we
      conducted a sub-analysis of HIV/AIDS knowledge, sexual behaviors, and injection
      drug risk behaviors among 2,199 Vietnamese respondents, including those reporting
      recent contact with an outreach worker and those who did not report contact. We
      found overall high levels of HIV/AIDS knowledge, low rates of needle sharing, and
      moderate to high rates of inconsistent condom use. Average knowledge scores of
      IDU were significantly higher than non-IDU for antiretroviral treatment
      knowledge, while MSM had significantly less knowledge of treatment compared to
      non-MSM. HIV/AIDS-related knowledge was not significantly associated with needle
      sharing practices. Knowledge was modestly but significantly associated with more
      consistent use of condoms with primary and commercial sex partners, even after
      controlling for contact with an outreach worker. Contact with an outreach worker
      was also an independent predictor of more consistent condom use. Outreach
      programs appear to play a meaningful role in changing sexual behavior, though the
      effect of outreach on IDU risk behaviors was less clear. More research is needed
      to understand the relationship between outreach programs and skill development,
      motivation, and use of referral services by most-at-risk populations in Vietnam.

PMID- 23173026
TI  - Today's Food System: How Healthy Is It?
AB  - With its focus on the quantity of production, often to the exclusion of other
      goals, today's food system is on an unsustainable course. The problem begins with
      and is driven by industrialized production of both crops and animals.
      Industrialization is a product of technological change, public policy, and, most
      recently, globalized trade. The lack of sustainability derives from reliance on
      the intensive use of nonrenewable and hard-to-renew resources-soil, antibiotics,
      fresh water, and fossil fuels, for example-but also from the waste and pollution
      created by the industrial model. For at least 50 years, American agriculture
      policies have promoted production of, and ultimately lower market prices for,
      commodity crops like corn, wheat, and soybeans. Over the last 3 decades in
      particular, these "cheap food" policies have exacerbated the negative impacts of
      an industrialized agriculture on the health of the agro-ecosystem, as well as on
      the health of the humans who must share and be sustained by it. Sustainability
      and health are two sides of the same food system coin. Policies that put US food
      production on more sustainable footing can help aid in public efforts to address
      the myriad crises confronting both the food and health systems.

PMID- 23173028
TI  - Food Systems and Public Health: The Community Perspective.
AB  - This article addresses the intersection of the food system and public health from
      the community perspective, based on the work of the HOPE Collaborative in
      Oakland, California. The HOPE Collaborative initiated intensive community
      outreach and engagement as part of its planning process to address inequitable
      access to healthy food in Oakland's most vulnerable neighborhoods. This effort
      involved two levels of community assessment and an inquiry into the potential of
      addressing both healthy food access and poverty through the construction of local
      food enterprise networks. Many unanswered questions remain. However, it seems
      clear in that in order to reduce health disparities in Oakland's most vulnerable
      neighborhoods, the community must address inequities in both access to healthy
      food and access to economic opportunity.

PMID- 23173027
TI  - Food Systems and Public Health Disparities.
AB  - The United States has set a national goal to eliminate health disparities. This
      article emphasizes the importance of food systems in generating and exacerbating
      health disparities in the United States and suggests avenues for reducing them.
      It presents a conceptual model showing how broad food system conditions interplay
      with community food environments-and how these relationships are filtered and
      refracted through prisms of social disparities to generate and exacerbate health
      disparities. Interactions with demand factors in the social environment are
      described. The article also highlights the separate food systems pathway to
      health disparities via environmental and occupational health effects of
      agriculture.

PMID- 23173029
TI  - Places to Intervene to Make Complex Food Systems More Healthy, Green, Fair, and
      Affordable.
AB  - A Food Systems and Public Health conference was convened in April 2009 to
      consider research supporting food systems that are healthy, green, fair, and
      affordable. We used a complex systems framework to examine the contents of
      background material provided to conference participants. Application of our
      intervention-level framework (paradigm, goals, system structure, feedback and
      delays, structural elements) enabled comparison of the conference themes of
      healthy, green, fair, and affordable. At the level of system structure suggested
      actions to achieve these goals are fairly compatible, including broad public
      discussion and implementation of policies and programs that support sustainable
      food production and distribution. At the level of paradigm and goals, the
      challenge of making healthy and green food affordable becomes apparent as some
      actions may be in conflict. Systems thinking can provide insight into the
      challenges and opportunities to act to make the food supply more healthy, green,
      fair, and affordable.

PMID- 23173030
TI  - Economic impact of HIV and antiretroviral therapy on education supply in high
      prevalence regions.
AB  - BACKGROUND: We set out to estimate, for the three geographical regions with the
      highest HIV prevalence, (sub-Saharan Africa [SSA], the Caribbean and the Greater
      Mekong sub-region of East Asia), the human resource and economic impact of HIV on
      the supply of education from 2008 to 2015, the target date for the achievement of
      Education For All (EFA), contrasting the continuation of access to care, support
      and Antiretroviral therapy (ART) to the scenario of universal access.
      METHODOLOGY/PRINCIPAL FINDINGS: A costed mathematical model of the impact of HIV
      and ART on teacher recruitment, mortality and absenteeism (Ed-SIDA) was run using
      best available data for 58 countries, and results aggregated by region. It was
      estimated that (1) The impact of HIV on teacher supply is sufficient to derail
      efforts to achieve EFA in several countries and universal access can mitigate
      this. (2) In SSA, the 2008 costs to education of HIV were about half of those
      estimated in 2002. Providing universal access for teachers in SSA is cost
      effective on education returns alone and provides a return of $3.99 on the
      dollar. (3) The impacts on education in the hyperendemic countries in Southern
      Africa will continue to increase to 2015 from its 2008 level, already the highest
      in the world. (4) If treatment roll-out is successful, numbers of HIV positive
      teachers are set to increase in all the regions studied.
      CONCLUSIONS/SIGNIFICANCE: The return on investing in care and support is also
      greater in those areas with highest impact. SSA requires increased investment in
      teacher support, testing and particularly ART if it is to achieve EFA. The
      situation for teachers in the Caribbean and East Asia is similar but on a smaller
      scale proportionate to the lower levels of infection and greater existing access
      to care and support.

PMID- 23173031
TI  - Disseminated breast cancer cells acquire a highly malignant and aggressive
      metastatic phenotype during metastatic latency in the bone.
AB  - BACKGROUND: Disseminated tumor cells (DTCs) in the bone marrow may exist in a
      dormant state for extended periods of time, maintaining the ability to
      proliferate upon activation, engraft at new sites, and form detectable
      metastases. However, understanding of the behavior and biology of dormant breast
      cancer cells in the bone marrow niche remains limited, as well as their potential
      involvement in tumor recurrence and metastasis. Therefore, the purpose of this
      study was to investigate the tumorigenicity and metastatic potential of dormant
      disseminated breast cancer cells (prior to activation) in the bone marrow.
      METHODOLOGY/PRINCIPAL FINDINGS: Total bone marrow, isolated from mice previously
      injected with tumorspheres into the mammary fat pad, was injected into the
      mammary fat pad of NUDE mice. As a negative control, bone marrow isolated from
      non-injected mice was injected into the mammary fat pad of NUDE mice. The
      resultant tumors were analyzed by immunohistochemistry for expression of
      epithelial and mesenchymal markers. Mouse lungs, livers, and kidneys were
      analyzed by H+E staining to detect metastases. The injection of bone marrow
      isolated from mice previously injected with tumorspheres into the mammary fat
      pad, resulted in large tumor formation in the mammary fat pad 2 months post
      injection. However, the injection of bone marrow isolated from non-injected mice
      did not result in tumor formation in the mammary fat pad. The DTC-derived tumors
      exhibited accelerated development of metastatic lesions within the lung, liver
      and kidney. The resultant tumors and the majority of metastatic lesions within
      the lung and liver exhibited a mesenchymal-like phenotype.
      CONCLUSIONS/SIGNIFICANCE: Dormant DTCs within the bone marrow are highly
      malignant upon injection into the mammary fat pad, with the accelerated
      development of metastatic lesions within the lung, liver and kidney. These
      results suggest the acquisition of a more aggressive phenotype of DTCs during
      metastatic latency within the bone marrow microenvironment.

PMID- 23173032
TI  - None of the six SNPs of IL28B could predict treatment responses in genotype 2
      chronic HCV infected patients by propensity score matching analysis.
AB  - BACKGROUND & AIMS: A combination of pegylated interferon-alpha and ribavirin (PR)
      is the standard therapy for patients with chronic hepatitis C. The impact of
      polymorphism of interleukin-28B (IL28B) on sustained virological response (SVR)
      to PR has been well documented in patients with CHC genotype-1 (GT1), but it is
      controversial in genotype-2 (GT2) CHC patients. This study investigated the
      predictability of six single nucleotide polymorphisms (SNP) of IL28B on the
      treatment responses of PR in patients with CHC GT2. METHOD: 197 CHC GT2
      consecutive patients who received PR treatment in our prospective cohort were
      enrolled. Hepatitis C virus (HCV) genotyping, quantification of HCV-RNA and
      genotyping of the ten SNPs of IL28B were performed. Six SNPs of IL28B were chosen
      for analysis. The propensity score matching (PSM) analysis was applied using
      patients with CHC GT1 in another prospective cohort as a positive comparison to
      avoid covariate bias. RESULTS: The distribution of the six SNPs was similar in
      GT1 and GT2 patients. Five of these SNPs had strong association with treatment
      responses in GT1 but not in GT2 patients. After PSM analysis, these five SNPs
      still showed strong association with rapid virological response (RVR), cEVR and
      SVR in GT1 and had no influence in GT2 patients. Furthermore, rs12979860 and
      baseline viral load were the predictors for both RVR and SVR in GT1 patients.
      However, only baseline viral load could predict RVR and SVR in GT2 patients. In
      addition, in patients without RVR, rs12979860 was the only predictor for SVR in
      GT1 but no predictor for SVR was found in GT2. CONCLUSIONS: The genetic
      polymorphisms of IL28B had no impact on treatment responses in GT2 patients.

PMID- 23173033
TI  - Hyaluronan fragments improve wound healing on in vitro cutaneous model through
      P2X7 purinoreceptor basal activation: role of molecular weight.
AB  - BACKGROUND: hyaluronan biopolymer is used in dermatology but the underlying
      mechanism and the impact of its molecular weight have not yet been investigated
      in skin wound healing. The aim of our work was to study the role of HA molecular
      weight in the proliferative phase of wound healing and to understand how this
      physiological biopolymer acts to promote wound healing on a human keratinocyte in
      vitro model. METHODOLOGY AND FINDINGS: wound healing closure was evaluated using
      scratch test assay, cell proliferation by counting cell with haemocytometer,
      expression of CD44 and ZO-1 (protein present in tight junctions specific of
      epithelia) using flow cytometry, and P2X7 receptor activation on living using a
      cytoflurometric method. Our study showed that medium hyaluronan fragment (MMW-HA,
      between 100 and 300 kDa) induced a significant increase in wound closure,
      increased ZO-1 protein expression and induced a slight activation of P2X7
      receptor, contrary to high (between 1000 and 1400 kDa) and low (between 5 and 20
      kDa) molecular hyaluronan fragments that had no healing effects. Basal activation
      of P2X7 receptor is already known to stimulate cell proliferation and this
      activation in our model plays a pivotal role in MMW-HA-induced wound healing.
      Indeed, we showed that use of BBG, a specific inhibitor of P2X7 receptor, blocked
      completely the beneficial effects of MMW-HA on wound healing. CONCLUSION: taken
      together, our results showed for the first time the relationship between P2X7
      receptor and hyaluronan in wound healing, and that topical use of MMW-HA
      (fragment between 100 and 300 kDa) could represent a new therapeutic strategy to
      promote healing.

PMID- 23173034
TI  - Oscillatory threshold logic.
AB  - In the 1940s, the first generation of modern computers used vacuum tube
      oscillators as their principle components, however, with the development of the
      transistor, such oscillator based computers quickly became obsolete. As the
      demand for faster and lower power computers continues, transistors are themselves
      approaching their theoretical limit and emerging technologies must eventually
      supersede them. With the development of optical oscillators and Josephson
      junction technology, we are again presented with the possibility of using
      oscillators as the basic components of computers, and it is possible that the
      next generation of computers will be composed almost entirely of oscillatory
      devices. Here, we demonstrate how coupled threshold oscillators may be used to
      perform binary logic in a manner entirely consistent with modern computer
      architectures. We describe a variety of computational circuitry and demonstrate
      working oscillator models of both computation and memory.

PMID- 23173035
TI  - Expression of small RNA in Aphis gossypii and its potential role in the
      resistance interaction with melon.
AB  - BACKGROUND: The regulatory role of small RNAs (sRNAs) in various biological
      processes is an active area of investigation; however, there has been limited
      information available on the role of sRNAs in plant-insect interactions. This
      study was designed to identify sRNAs in cotton-melon aphid (Aphis gossypii)
      during the Vat-mediated resistance interaction with melon (Cucumis melo).
      METHODOLOGY/PRINCIPAL FINDINGS: The role of miRNAs was investigated in response
      to aphid herbivory, during both resistant and susceptible interactions. sRNA
      libraries made from A. gossypii tissues feeding on Vat+ and Vat- plants revealed
      an unexpected abundance of 27 nt long sRNA sequences in the aphids feeding on
      Vat+ plants. Eighty-one conserved microRNAs (miRNAs), twelve aphid-specific
      miRNAs, and nine novel candidate miRNAs were also identified. Plant miRNAs found
      in the aphid libraries were most likely ingested during phloem feeding. The
      presence of novel miRNAs was verified by qPCR experiments in both resistant Vat+
      and susceptible Vat- interactions. The comparative analyses revealed that novel
      miRNAs were differentially regulated during the resistant and susceptible
      interactions. Gene targets predicted for the miRNAs identified in this study by
      in silico analyses revealed their involvement in morphogenesis and anatomical
      structure determination, signal transduction pathways, cell differentiation and
      catabolic processes. CONCLUSION/SIGNIFICANCE: In this study, conserved and novel
      miRNAs were reported in A. gossypii. Deep sequencing data showed differences in
      the abundance of miRNAs and piRNA-like sequences in A. gossypii. Quantitative RT
      PCR revealed that A. gossypii miRNAs were differentially regulated during
      resistant and susceptible interactions. Aphids can also ingest plant miRNAs
      during phloem feeding that are stable in the insect.

PMID- 23173036
TI  - Plants from Brazilian Cerrado with potent tyrosinase inhibitory activity.
AB  - The increased amount of melanin leads to skin disorders such as age spots,
      freckles, melasma and malignant melanoma. Tyrosinase is known to be the key
      enzyme in melanin production. Plants and their extracts are inexpensive and rich
      resources of active compounds that can be utilized to inhibit tyrosinase as well
      as can be used for the treatment of dermatological disorders associated with
      melanin hyperpigmentation. Using in vitro tyrosinase inhibitory activity assay,
      extracts from 13 plant species from Brazilian Cerrado were evaluated. The results
      showed that Pouteria torta and Eugenia dysenterica extracts presented potent in
      vitro tyrosinase inhibition compared to positive control kojic acid. Ethanol
      extract of Eugenia dysenterica leaves showed significant (p<0.05) tyrosinase
      inhibitory activity exhibiting the IC50 value of 11.88 ug/mL, compared to kojic
      acid (IC50 value of 13.14 ug/mL). Pouteria torta aqueous extract leaves also
      showed significant inhibitory activity with IC50 value of 30.01 ug/mL. These
      results indicate that Pouteria torta and Eugenia dysenterica extracts and their
      isolated constituents are promising agents for skin-whitening or
      antimelanogenesis formulations.

PMID- 23173037
TI  - Potent inhibition of late stages of hepadnavirus replication by a modified cell
      penetrating peptide.
AB  - Cationic cell-penetrating peptides (CPPs) and their lipid domain-conjugates
      (CatLip) are agents for the delivery of (uncharged) biologically active molecules
      into the cell. Using infection and transfection assays we surprisingly discovered
      that CatLip peptides were able to inhibit replication of Duck Hepatitis B Virus
      (DHBV), a reference model for human HBV. Amongst twelve CatLip peptides we
      identified Deca-(Arg)8 having a particularly potent antiviral activity, leading
      to a drastic inhibition of viral particle secretion without detectable toxicity.
      Inhibition of virion secretion was correlated with a dose-dependent increase in
      intracellular viral DNA. Deca-(Arg)8 peptide did neither interfere with DHBV
      entry, nor with formation of mature nucleocapsids nor with their travelling to
      the nucleus. Instead, Deca-(Arg)8 caused envelope protein accumulation in large
      clusters as revealed by confocal laser scanning microscopy indicating severe
      structural changes of preS/S. Sucrose gradient analysis of supernatants from Deca
      (Arg)8-treated cells showed unaffected naked viral nucleocapsids release, which
      was concomitant with a complete arrest of virion and surface protein-containing
      subviral particle secretion. This is the first report showing that a CPP is able
      to drastically block hepadnaviral release from infected cells by altering late
      stages of viral morphogenesis via interference with enveloped particle formation,
      without affecting naked nucleocapsid egress, thus giving a view inside the mode
      of inhibition. Deca-(Arg)8 may be a useful tool for elucidating the hepadnaviral
      secretory pathway, which is not yet fully understood. Moreover we provide the
      first evidence that a modified CPP displays a novel antiviral mechanism targeting
      another step of viral life cycle compared to what has been so far described for
      other enveloped viruses.

PMID- 23173038
TI  - Behavioural distinction between strategic control and spatial realignment during
      visuomotor adaptation in a viewing window task.
AB  - We must frequently adapt our movements in order to successfully perform motor
      tasks. These visuomotor adaptations can occur with or without our awareness and
      so, have generally been described by two mechanisms: strategic control and
      spatial realignment. Strategic control is a conscious modification used when
      discordance between an intended and actual movement is observed. Spatial
      realignment is an unconscious recalibration in response to subtle differences
      between an intended and efferent movement. Traditional methods of investigating
      visuomotor adaptation often involve simplistic, repetitive motor goals and so may
      be vulnerable to subject boredom or expectation. Our laboratory has recently
      developed a novel, engaging computer-based task, the Viewing Window, to
      investigate visuomotor adaptation to large, apparent distortions. Here, we
      contrast behavioural measures of visuomotor adaptation during the Viewing Window
      task when either gradual progressive rotations or large, sudden rotations are
      introduced in order to demonstrate that this paradigm can be utilized to
      investigate both strategic control and spatial realignment. The gradual rotation
      group demonstrated significantly faster mean velocities and spent significantly
      less time off the object compared to the sudden rotation group. These differences
      demonstrate adaptation to the distortion using spatial realignment. Scan paths
      revealed greater after-effects in the gradual rotation group reflected by greater
      time spent scanning areas off of the object. These results demonstrate the
      ability to investigate both strategic control and spatial realignment. Thus, the
      Viewing Window provides a powerful engaging tool for investigating the neural
      basis of visuomotor adaptation and impairment following injury and disease.

PMID- 23173039
TI  - Non-injurious neonatal hypoxia confers resistance to brain senescence in aged
      male rats.
AB  - Whereas brief acute or intermittent episodes of hypoxia have been shown to exert
      a protective role in the central nervous system and to stimulate neurogenesis,
      other studies suggest that early hypoxia may constitute a risk factor that
      influences the future development of mental disorders. We therefore investigated
      the effects of a neonatal "conditioning-like" hypoxia (100% N2, 5 min) on the
      brain and the cognitive outcomes of rats until 720 days of age (physiologic
      senescence). We confirmed that such a short hypoxia led to brain neurogenesis
      within the ensuing weeks, along with reduced apoptosis in the hippocampus
      involving activation of Erk1/2 and repression of p38 and death-associated protein
      (DAP) kinase. At 21 days of age, increased thicknesses and cell densities were
      recorded in various subregions, with strong synapsin activation. During aging,
      previous exposure to neonatal hypoxia was associated with enhanced memory
      retrieval scores specifically in males, better preservation of their brain
      integrity than controls, reduced age-related apoptosis, larger hippocampal cell
      layers, and higher expression of glutamatergic and GABAergic markers. These
      changes were accompanied with a marked expression of synapsin proteins, mainly of
      their phosphorylated active forms which constitute major players of synapse
      function and plasticity, and with increases of their key regulators, i.e. Erk1/2,
      the transcription factor EGR-1/Zif-268 and Src kinase. Moreover, the
      significantly higher interactions between PSD-95 scaffolding protein and NMDA
      receptors measured in the hippocampus of 720-day-old male animals strengthen the
      conclusion of increased synaptic functional activity and plasticity associated
      with neonatal hypoxia. Thus, early non-injurious hypoxia may trigger beneficial
      long term effects conferring higher resistance to senescence in aged male rats,
      with a better preservation of cognitive functions.

PMID- 23173041
TI  - Comparison of journal self-citation rates between some Chinese and non-Chinese
      international journals.
AB  - BACKGROUND: The past 3 decades have witnessed a boost in science development in
      China; in parallel, more and more Chinese scientific journals are indexed by the
      Journal Citation Reports issued by Thomson Reuters (SCI). Evaluation of the
      performance of these Chinese SCI journals is necessary and helpful to improve
      their quality. This study aimed to evaluate these journals by calculating various
      journal self-citation rates, which are important parameters influencing a journal
      impact factor. METHODOLOGY/PRINCIPAL FINDINGS: We defined three journal self
      citation rates, and studied these rates for 99 Chinese scientific journals,
      almost exhausting all Chinese SCI journals currently available. Likewise, we
      selected 99 non-Chinese international (abbreviated as 'world') journals, with
      each being in the same JCR subject category and having similar impact factors as
      their Chinese counterparts. Generally, Chinese journals tended to be higher in
      all the three self-citation rates than world journal counterparts. Particularly,
      a few Chinese scientific journals had much higher self-citation rates.
      CONCLUSIONS/SIGNIFICANCE: Our results show that generally Chinese scientific
      journals have higher self-citation rates than those of world journals.
      Consequently, Chinese scientific journals tend to have lower visibility and are
      more isolated in the relevant fields. Considering the fact that sciences are
      rapidly developing in China and so are Chinese scientific journals, we expect
      that the differences of journal self-citation rates between Chinese and world
      scientific journals will gradually disappear in the future. Some suggestions to
      solve the problems are presented.

PMID- 23173040
TI  - Osteoclasts in multiple myeloma are derived from Gr-1+CD11b+myeloid-derived
      suppressor cells.
AB  - Osteoclasts play a key role in the development of cancer-associated osteolytic
      lesions. The number and activity of osteoclasts are often enhanced by tumors.
      However, the origin of osteoclasts is unknown. Myeloid-derived suppressor cells
      (MDSCs) are one of the pre-metastatic niche components that are induced to expand
      by tumor cells. Here we show that the MDSCs can differentiate into mature and
      functional osteoclasts in vitro and in vivo. Inoculation of 5TGM1-GFP myeloma
      cells into C57BL6/KaLwRij mice led to a significant expansion of MDSCs in blood,
      spleen, and bone marrow over time. When grown in osteoclastogenic media in vitro,
      MDSCs from tumor-challenged mice displayed 14 times greater potential to
      differentiate into mature and functional osteoclasts than those from non-tumor
      controls. Importantly, MDSCs from tumor-challenged LacZ transgenic mice
      differentiated into LacZ+osteoclasts in vivo. Furthermore, a significant increase
      in tumor burden and bone loss accompanied by increased number of osteoclasts was
      observed in mice co-inoculated with tumor-challenged MDSCs and 5TGM1 cells
      compared to the control animals received 5TGM1 cells alone. Finally, treatment of
      MDSCs from myeloma-challenged mice with Zoledronic acid (ZA), a potent inhibitor
      of bone resorption, inhibited the number of osteoclasts formed in MDSC cultures
      and the expansion of MDSCs and bone lesions in mice. Collectively, these data
      provide in vitro and in vivo evidence that tumor-induced MDSCs exacerbate cancer
      associated bone destruction by directly serving as osteoclast precursors.

PMID- 23173043
TI  - Improved gravitation field algorithm and its application in hierarchical
      clustering.
AB  - BACKGROUND: Gravitation field algorithm (GFA) is a new optimization algorithm
      which is based on an imitation of natural phenomena. GFA can do well both for
      searching global minimum and multi-minima in computational biology. But GFA needs
      to be improved for increasing efficiency, and modified for applying to some
      discrete data problems in system biology. METHOD: An improved GFA called IGFA was
      proposed in this paper. Two parts were improved in IGFA. The first one is the
      rule of random division, which is a reasonable strategy and makes running time
      shorter. The other one is rotation factor, which can improve the accuracy of
      IGFA. And to apply IGFA to the hierarchical clustering, the initial part and the
      movement operator were modified. RESULTS: Two kinds of experiments were used to
      test IGFA. And IGFA was applied to hierarchical clustering. The global minimum
      experiment was used with IGFA, GFA, GA (genetic algorithm) and SA (simulated
      annealing). Multi-minima experiment was used with IGFA and GFA. The two
      experiments results were compared with each other and proved the efficiency of
      IGFA. IGFA is better than GFA both in accuracy and running time. For the
      hierarchical clustering, IGFA is used to optimize the smallest distance of genes
      pairs, and the results were compared with GA and SA, singular-linkage clustering,
      UPGMA. The efficiency of IGFA is proved.

PMID- 23173042
TI  - Matrix metalloproteinases in a sea urchin ligament with adaptable mechanical
      properties.
AB  - Mutable collagenous tissues (MCTs) of echinoderms show reversible changes in
      tensile properties (mutability) that are initiated and modulated by the nervous
      system via the activities of cells known as juxtaligamental cells. The molecular
      mechanism underpinning this mechanical adaptability has still to be elucidated.
      Adaptable connective tissues are also present in mammals, most notably in the
      uterine cervix, in which changes in stiffness result partly from changes in the
      balance between matrix metalloproteinases (MMPs) and tissue inhibitors of
      metalloproteinases (TIMPs). There have been no attempts to assess the potential
      involvement of MMPs in the echinoderm mutability phenomenon, apart from studies
      dealing with a process whose relationship to the latter is uncertain. In this
      investigation we used the compass depressor ligaments (CDLs) of the sea-urchin
      Paracentrotus lividus. The effect of a synthetic MMP inhibitor - galardin - on
      the biomechanical properties of CDLs in different mechanical states ("standard",
      "compliant" and "stiff") was evaluated by dynamic mechanical analysis, and the
      presence of MMPs in normal and galardin-treated CDLs was determined semi
      quantitatively by gelatin zymography. Galardin reversibly increased the stiffness
      and storage modulus of CDLs in all three states, although its effect was
      significantly lower in stiff than in standard or compliant CDLs. Gelatin
      zymography revealed a progressive increase in total gelatinolytic activity
      between the compliant, standard and stiff states, which was possibly due
      primarily to higher molecular weight components resulting from the inhibition and
      degradation of MMPs. Galardin caused no change in the gelatinolytic activity of
      stiff CDLs, a pronounced and statistically significant reduction in that of
      standard CDLs, and a pronounced, but not statistically significant, reduction in
      that of compliant CDLs. Our results provide evidence that MMPs may contribute to
      the variable tensility of the CDLs, in the light of which we provide an updated
      hypothesis for the regulatory mechanism controlling MCT mutability.

PMID- 23173044
TI  - Deletion of CDKAL1 affects high-fat diet-induced fat accumulation and glucose
      stimulated insulin secretion in mice, indicating relevance to diabetes.
AB  - BACKGROUND/OBJECTIVE: The CDKAL1 gene is among the best-replicated susceptibility
      loci for type 2 diabetes, originally identified by genome-wide association
      studies in humans. To clarify a physiological importance of CDKAL1, we examined
      effects of a global Cdkal1-null mutation in mice and also evaluated the influence
      of a CDKAL1 risk allele on body mass index (BMI) in Japanese subjects. METHODS:
      In Cdkal1-deficient (Cdkal1-/-) mice, we performed oral glucose tolerance test,
      insulin tolerance test, and perfusion experiments with and without high-fat
      feeding. Based on the findings in mice, we tested genetic association of CDKAL1
      variants with BMI, as a measure of adiposity, and type 2 diabetes in Japanese.
      PRINCIPAL FINDINGS: On a standard diet, Cdkal1-/- mice were modestly lighter in
      weight than wild-type littermates without major alterations in glucose
      metabolism. On a high fat diet, Cdkal1-/- mice showed significant reduction in
      fat accumulation (17% reduction in %intraabdominal fat, P = 0.023 vs. wild-type
      littermates) with less impaired insulin sensitivity at an early stage. High fat
      feeding did not potentiate insulin secretion in Cdkal1-/- mice (1.0-fold),
      contrary to the results in wild-type littermates (1.6-fold, P<0.01). Inversely,
      at a later stage, Cdkal1-/- mice showed more prominent impairment of insulin
      sensitivity and glucose tolerance. mRNA expression analysis indicated that Scd1
      might function as a critical mediator of the altered metabolism in Cdkal1-/-
      mice. In accordance with the findings in mice, a nominally significant (P<0.05)
      association between CDKAL1 rs4712523 and BMI was replicated in 2 Japanese general
      populations comprising 5,695 and 12,569 samples; the risk allele for type 2
      diabetes was also associated with decreased BMI. CONCLUSIONS: Cdkal1 gene
      deletion is accompanied by modestly impaired insulin secretion and longitudinal
      fluctuations in insulin sensitivity during high-fat feeding in mice. CDKAL1 may
      affect such compensatory mechanisms regulating glucose homeostasis through
      interaction with diet.

PMID- 23173045
TI  - Position-specific analysis and prediction for protein lysine acetylation based on
      multiple features.
AB  - Protein lysine acetylation is a type of reversible post-translational
      modification that plays a vital role in many cellular processes, such as
      transcriptional regulation, apoptosis and cytokine signaling. To fully decipher
      the molecular mechanisms of acetylation-related biological processes, an initial
      but crucial step is the recognition of acetylated substrates and the
      corresponding acetylation sites. In this study, we developed a position-specific
      method named PSKAcePred for lysine acetylation prediction based on support vector
      machines. The residues around the acetylation sites were selected or excluded
      based on their entropy values. We incorporated features of amino acid composition
      information, evolutionary similarity and physicochemical properties to predict
      lysine acetylation sites. The prediction model achieved an accuracy of 79.84% and
      a Matthews correlation coefficient of 59.72% using the 10-fold cross-validation
      on balanced positive and negative samples. A feature analysis showed that all
      features applied in this method contributed to the acetylation process. A
      position-specific analysis showed that the features derived from the critical
      neighboring residues contributed profoundly to the acetylation site
      determination. The detailed analysis in this paper can help us to understand more
      of the acetylation mechanism and can provide guidance for the related
      experimental validation.

PMID- 23173046
TI  - Unraveling the phylogenetic relationships of the Eccoptochilinae, an enigmatic
      array of ordovician cheirurid trilobites.
AB  - The Cheiruridae are a diverse group of trilobites and several subfamilies within
      the clade have been the focus of recent phylogenetic studies. This paper focuses
      on the relationships of one of those subfamilies, the Ordovician Eccoptochilinae.
      We analyze sixteen species from six genera within the traditionally defined
      group, using the pilekiid Anacheirurus frederici as an outgroup. To assess the
      monophyly of the Eccoptochilinae seven sphaerexochine species, Kawina arnoldi,
      Sphaerexochus arenosus, S. atacius, S. latifrons, S. mirus, S. parvus, and S.
      scabridus were included in the analysis as well. The results of this analysis
      show that the genus Eccoptochile represents a paraphyletic grade and species
      traditionally assigned to Parasphaerexochus and Skelipyx plot within
      Pseudosphaerexochus. Also, representative species of Sphaerexochinae plot within
      the traditionally defined Eccoptochilinae, suggesting Eccoptochilinae itself is
      paraphyletic. To resolve this, we propose all species of Pseudosphaerexochus be
      placed within Sphaerexochinae and Eccoptochilinae be restricted to a monotypic
      Eccoptochile clavigera.

PMID- 23173047
TI  - Soybean endo-beta-mannanase GmMAN1 is not associated with leaf abscission, but
      might be involved in the response to wounding.
AB  - The objective of this work is to investigate the relationship between endo-beta
      mannanase and leaf abscission, and response to wounding in soybean (Glycine max).
      An endo-beta-mannanase gene GmMAN1 was cloned from the abscission zone in petiole
      explants, and was heterologously expressed in E. coli. Polyclonal antibodies were
      raised against the fusion protein. The increases in activity, isoform numbers,
      and amounts of transcripts and proteins of GmMAN1 were found not only in the
      abscission zone but also in the non-abscission zone during petiole abscission in
      the explants, but not in these two tissues during leaf abscission artificially
      induced by ethephon treatment in the intact plants. The changes in endo-beta
      mannanase expression patterns in these two tissues were probably induced by the
      inherent mechanical wounding during the preparation of explants. When soybean
      plants were wounded by removing half of the leaf blade of the first pair of true
      leaves, the transcripts and proteins of GmMAN1 were induced in the leaves and
      stem, leading to the increases in enzyme activity and isoform numbers in them. It
      is concluded that the soybean endo-beta-mannanase GmMAN1 is not associated with
      leaf abscission, but might be involved in the response to wounding.

PMID- 23173048
TI  - Seasonal response of grasslands to climate change on the Tibetan Plateau.
AB  - BACKGROUND: Monitoring vegetation dynamics and their responses to climate change
      has been the subject of considerable research. This paper aims to detect change
      trends in grassland activity on the Tibetan Plateau between 1982 and 2006 and
      relate these to changes in climate. METHODOLOGY/PRINCIPAL FINDINGS: Grassland
      activity was analyzed by evaluating remotely sensed Normalized Difference
      Vegetation Index (NDVI) data collected at 15-day intervals between 1982 and 2006.
      The timings of vegetation stages (start of green-up, beginning of the growing
      season, plant maturity, start of senescence and end of the growing season) were
      assessed using the NDVI ratio method. Mean NDVI values were determined for major
      vegetation stages (green-up, fast growth, maturity and senescence). All
      vegetation variables were linked with datasets of monthly temperature and
      precipitation, and correlations between variables were established using Partial
      Least Squares regression. Most parts of the Tibetan Plateau showed significantly
      increasing temperatures, as well as clear advances in late season phenological
      stages by several weeks. Rainfall trends and significant long-term changes in
      early season phenology occurred on small parts of the plateau. Vegetation
      activity increased significantly for all vegetation stages. Most of these changes
      were related to increasing temperatures during the growing season and in some
      cases during the previous winter. Precipitation effects appeared less pronounced.
      Warming thus appears to have shortened the growing season, while increasing
      vegetation activity. CONCLUSIONS/SIGNIFICANCE: Shortening of the growing season
      despite a longer thermally favorable period implies that vegetation on the
      Tibetan Plateau is unable to exploit additional thermal resources availed by
      climate change. Ecosystem composition may no longer be well attuned to the local
      temperature regime, which has changed rapidly over the past three decades. This
      apparent lag of the vegetation assemblage behind changes in climate should be
      taken into account when projecting the impacts of climate change on ecosystem
      processes.

PMID- 23173049
TI  - Defects in ultrasonic vocalization of cadherin-6 knockout mice.
AB  - BACKGROUND: Although some molecules have been identified as responsible for human
      language disorders, there is still little information about what molecular
      mechanisms establish the faculty of human language. Since mice, like songbirds,
      produce complex ultrasonic vocalizations for intraspecific communication in
      several social contexts, they can be good mammalian models for studying the
      molecular basis of human language. Having found that cadherins are involved in
      the vocal development of the Bengalese finch, a songbird, we expected cadherins
      to also be involved in mouse vocalizations. METHODOLOGY/PRINCIPAL FINDINGS: To
      examine whether similar molecular mechanisms underlie the vocalizations of
      songbirds and mammals, we categorized behavioral deficits including vocalization
      in cadherin-6 knockout mice. Comparing the ultrasonic vocalizations of cadherin-6
      knockout mice with those of wild-type controls, we found that the peak frequency
      and variations of syllables were differed between the mutant and wild-type mice
      in both pup-isolation and adult-courtship contexts. Vocalizations during male
      male aggression behavior, in contrast, did not differ between mutant and wild
      type mice. Open-field tests revealed differences in locomotors activity in both
      heterozygote and homozygote animals and no difference in anxiety behavior.
      CONCLUSIONS/SIGNIFICANCE: Our results suggest that cadherin-6 plays essential
      roles in locomotor activity and ultrasonic vocalization. These findings also
      support the idea that different species share some of the molecular mechanisms
      underlying vocal behavior.

PMID- 23173050
TI  - BCL::Fold--de novo prediction of complex and large protein topologies by assembly
      of secondary structure elements.
AB  - Computational de novo protein structure prediction is limited to small proteins
      of simple topology. The present work explores an approach to extend beyond the
      current limitations through assembling protein topologies from idealized alpha
      helices and beta-strands. The algorithm performs a Monte Carlo Metropolis
      simulated annealing folding simulation. It optimizes a knowledge-based potential
      that analyzes radius of gyration, beta-strand pairing, secondary structure
      element (SSE) packing, amino acid pair distance, amino acid environment, contact
      order, secondary structure prediction agreement and loop closure. Discontinuation
      of the protein chain favors sampling of non-local contacts and thereby creation
      of complex protein topologies. The folding simulation is accelerated through
      exclusion of flexible loop regions further reducing the size of the
      conformational search space. The algorithm is benchmarked on 66 proteins with
      lengths between 83 and 293 amino acids. For 61 out of these proteins, the best
      SSE-only models obtained have an RMSD100 below 8.0 A and recover more than 20% of
      the native contacts. The algorithm assembles protein topologies with up to 215
      residues and a relative contact order of 0.46. The method is tailored to be used
      in conjunction with low-resolution or sparse experimental data sets which often
      provide restraints for regions of defined secondary structure.

PMID- 23173051
TI  - BCL::Score--knowledge based energy potentials for ranking protein models
      represented by idealized secondary structure elements.
AB  - The topology of most experimentally determined protein domains is defined by the
      relative arrangement of secondary structure elements, i.e. alpha-helices and beta
      strands, which make up 50-70% of the sequence. Pairing of beta-strands defines
      the topology of beta-sheets. The packing of side chains between alpha-helices and
      beta-sheets defines the majority of the protein core. Often, limited experimental
      datasets restrain the position of secondary structure elements while lacking
      detail with respect to loop or side chain conformation. At the same time the
      regular structure and reduced flexibility of secondary structure elements make
      these interactions more predictable when compared to flexible loops and side
      chains. To determine the topology of the protein in such settings, we introduce a
      tailored knowledge-based energy function that evaluates arrangement of secondary
      structure elements only. Based on the amino acid C(beta) atom coordinates within
      secondary structure elements, potentials for amino acid pair distance, amino acid
      environment, secondary structure element packing, beta-strand pairing, loop
      length, radius of gyration, contact order and secondary structure prediction
      agreement are defined. Separate penalty functions exclude conformations with
      clashes between amino acids or secondary structure elements and loops that cannot
      be closed. Each individual term discriminates for native-like protein structures.
      The composite potential significantly enriches for native-like models in three
      different databases of 10,000-12,000 protein models in 80-94% of the cases. The
      corresponding application, "BCL::ScoreProtein," is available at
      www.meilerlab.org.

PMID- 23173052
TI  - Return to work after percutaneous coronary intervention: the predictive value of
      self-reported health compared to clinical measures.
AB  - AIMS: Coronary heart disease is prevalent in the working-age population.
      Traditional outcome measures like mortality and readmission are of importance to
      evaluate the prognosis but are hardly sufficient. Ability to work is an
      additional outcome of clinical and societal significance. We describe trends and
      predictors of Return To Work (RTW) after PCI and describe a possible benefit
      using patient-reported measures in risk stratification of RTW. METHODS: A total
      of 1585 patients aged less than 67 years treated with PCI in 2006-2008 at the
      Aarhus University Hospital were enrolled. Clinical information was provided
      through the West Denmark Heart Registry, and 4 weeks after PCI we mailed a
      questionnaire regarding self-rated health (response rate 83.5%). RTW was defined
      at weekly basis using extensive register data on transfer payments. Predictors of
      RTW were analysed as time to event. ROC curves constructed by logistic regression
      of predicting variables were evaluated by the c-statistic. RESULTS: Four weeks
      before PCI 50% of the patients were working; the corresponding figures were 25%
      after 4 weeks, 36% after 12 weeks, and 43% after one year. The patients' self
      rated health one month after the procedure was a significant better predictor of
      RTW compared to other variables including LVEF, both at short (12 weeks) and long
      (one year) term. CONCLUSIONS: The patient's self-rated health four weeks after
      the procedure was a stronger predictor than left ventricular ejection fraction
      (LVEF), and consequently useful when patients seek medical advice with respect to
      RWT.

PMID- 23173053
TI  - CXC-type chemokines promote myofibroblast phenoconversion and prostatic fibrosis.
AB  - Recent studies from our group suggest that extracellular matrix (ECM) deposition
      and fibrosis characterize the peri-urethral prostate tissues of some men
      suffering from Lower Urinary Tract Symptoms (LUTS) and that fibrosis may be a
      contributing factor to the etiology of LUTS. Fibrosis can generally be regarded
      as an errant wound-healing process in response to chronic inflammation, and
      several studies have shown that the aging prostate tissue microenvironment is
      rich with inflammatory cells and proteins. However, it is unclear whether these
      same inflammatory proteins, particularly CXC-type chemokines, can mediate
      myofibroblast phenoconversion and the ECM deposition necessary for the
      development of prostatic tissue fibrosis. To examine this, immortalized and
      primary prostate stromal fibroblasts treated with TGF-beta1, CXCL5, CXCL8, or
      CXCL12 were evaluated morphologically by microscopy, by immunofluorescence and
      qRT-PCR for alphaSMA, collagen 1, vimentin, calponin, and tenascin protein and
      transcript expression, and by gel contraction assays for functional myofibroblast
      phenoconversion. The results of these studies showed that that immortalized and
      primary prostate stromal fibroblasts are induced to express collagen 1 and 3 and
      alphaSMA gene transcripts and proteins and to undergo complete and functional
      myofibroblast phenoconversion in response to CXC-type chemokines, even in the
      absence of exogenous TGF-beta1. Moreover, CXCL12-mediated myofibroblast
      phenoconversion can be completely abrogated by inhibition of the CXCL12 receptor,
      CXCR4. These findings suggest that CXC-type chemokines, which comprise
      inflammatory proteins known to be highly expressed in the aging prostate, can
      efficiently and completely mediate myofibroblast phenoconversion and may thereby
      promote fibrotic changes in prostate tissue architecture associated with the
      development and progression of male lower urinary tract dysfunction.

PMID- 23173054
TI  - Oral human papillomavirus in men having sex with men: risk-factors and sampling.
AB  - BACKGROUND: Human papillomavirus (HPV)-associated oropharyngeal squamous cell
      carcinoma is becoming more common. We examined prevalence and risk factors for
      oral HPV among men who have sex with men (MSM) and compared sampling and
      transport methods. METHODS: In 2010, 500 MSM (249 HIV-positive) attending
      Melbourne Sexual Health Centre answered a questionnaire, swabbed their mouth and
      throat and collected a gargled oral rinse sample. Half the oral rinse was
      transported absorbed in a tampon (to enable postage). HPV was detected by
      polymerase chain reaction, and genotyped by Roche Linear Array(r). Men with HPV
      16 or 18 were retested after six months. RESULTS: Any HPV genotype was detected
      in 19% (95% confidence intervals (CI) 15-25%) of HIV-infected men and 7% (95% CI
      4-11%) of HIV-negative men (p<0.001), and HPV 16 was detected in 4.4% (95% CI 2
      8%) of HIV-infected men and 0.8% (0.1-2.8%) of HIV-negative men. Oral HPV was
      associated with: current smoking (adjusted odds ratio (aOR) 2.2 (95%CI: 1.2
      3.9)), time since tooth-brushing (aOR per hour 0.87, 95%CI: 0.8-0.96) and number
      of lifetime tongue-kissing partners aOR 3.2 95%CI: (1.2-8.4) for 26-100 partners
      and 4.9 95%CI: (1.9-12.5) for>100 partners. Lifetime oral-penile sex partner
      numbers were significantly associated in a separate model: aOR 2.8(1.2-6.3) for
      26-100 partners and 3.2(1.4-7.2) for>100 partners. HPV 16 and 18 persisted in 10
      of 12 men after a median six months. Sensitivities of sampling methods compared
      to all methods combined were: oral rinse 97%, tampon-absorbed oral rinse 69%,
      swab 32%. CONCLUSIONS: Oral HPV was associated with HIV infection, smoking,
      recent tooth-brushing, and more lifetime tongue-kissing and oral sex partners.
      The liquid oral rinse sample was more sensitive than a tampon-absorbed oral rinse
      or a self-collected swab.

PMID- 23173055
TI  - Intense resistance exercise induces early and transient increases in ryanodine
      receptor 1 phosphorylation in human skeletal muscle.
AB  - BACKGROUND: While ryanodine receptor 1 (RyR1) critically contributes to skeletal
      muscle contraction abilities by mediating Ca2+ion oscillation between
      sarcoplasmatic and myofibrillar compartments, AMP-activated protein kinase (AMPK)
      senses contraction-induced energetic stress by phosphorylation at Thr172.
      Phosphorylation of RyR1 at serine2843 (pRyR1Ser2843) results in leaky RyR1
      channels and impaired Ca2+homeostasis. Because acute resistance exercise exerts
      decreased contraction performance in skeletal muscle, preceded by high rates of
      Ca2+-oscillation and energetic stress, intense myofiber contractions may induce
      increased RyR1 and AMPK phosphorylation. However, no data are available regarding
      the time-course and magnitude of early RyR1 and AMPK phosphorylation in human
      myofibers in response to acute resistance exercise. PURPOSE: Determine the
      effects and early time-course of resistance exercise on pRyR1Ser2843 and
      pAMPKThr172 in type I and II myofibers. METHODS: 7 male subjects (age 23+/-2
      years, height: 185+/-7 cm, weight: 82+/-5 kg) performed 3 sets of 8 repetitions
      of maximum eccentric knee extensions. Muscle biopsies were taken at rest, 15, 30
      and 60 min post exercise. pRyR1Ser2843 and pAMPKThr172 levels were determined by
      western blot and semi-quantitative immunohistochemistry techniques. RESULTS:
      While total RyR1 and total AMPK levels remained unchanged, RyR1 was significantly
      more abundant in type II than type I myofibers. pRyR1Ser2843 increased 15 min and
      peaked 30 min (p<0.01) post exercise in both myofiber types. Type I fibers showed
      relatively higher increases in pRyR1Ser2843 levels than type II myofibers and
      remained elevated up to 60 min post resistance exercise (p<0.05). pAMPKThr172
      also increased 15 to 30 min post exercise (p<0.01) in type I and II myofibers and
      in whole skeletal muscle. CONCLUSION: Resistance exercise induces acutely
      increased pRyR1Ser2843 and concomitantly pAMPKThr172 levels for up to 30 min in
      resistance exercised myofibers. This provides a time-course by which pRyR1Ser2843
      can mechanistically impact Ca2+handling properties and consequently induce
      reduced myofiber contractility beyond immediate fatiguing mechanisms.

PMID- 23173056
TI  - A tale of two tissues: AtGH9C1 is an endo-beta-1,4-glucanase involved in root
      hair and endosperm development in Arabidopsis.
AB  - Arabidopsis AtGH9C1 is an endo-beta-1,4-glucanase possessing a carbohydrate
      binding domain (CBM49). Analysis of AtGH9C1 expression by promoter-reporter GUS,
      RT-PCR, public transcriptome databases and GFP protein tagging demonstrated a
      high and selective expression of AtGH9C1 in root hairs and in the endosperm.
      Expression in root hair cells started prior to bulge formation and continued
      during hair elongation. AtGH9C1 expression increased with treatments that
      increase density (ACC) or length (sucrose) of root hairs. Expression in the
      endosperm extended sequentially to the micropylar, peripheral and chalazal
      compartments. A mutant with reduced AtGH9C1 expression had a delay in germination
      and a marked reduction in root hair presence. Complementation of the mutant
      partially improved both germination and root hair density. Experiments with
      ectopically expressed AtGH9C1-GFP with and without the CBM49, demonstrated that
      both forms of the protein are secreted and that CBM49 targets the protein to
      specific regions of the cell wall, but what makes these regions special is still
      unknown. The amino acid alignment of angiosperm GH9 genes with C-terminal
      extensions illustrate that AtGH9C1 belongs to a different clade than its tomato
      homolog, S1GH9C1. The latter has a CBM49 that was shown to bind crystalline
      cellulose. We suggest that AtGH9C1 is associated with the weakening of the cell
      wall during formation and growth of the root hair as well as with the sequential
      anterior-posterior breakdown of the endosperm cell wall that provides space for
      the growing embryo. Thus, is likely that the CBM49 of AtGH9C1 recognizes a form
      of cellulose or glucan polymer that is prevalent in the wall of these specialized
      tissues and that is different than the one recognized by S1GH9C1.

PMID- 23173057
TI  - Spatio-temporal variation in predation by urban domestic cats (Felis catus) and
      the acceptability of possible management actions in the UK.
AB  - Urban domestic cat (Felis catus) populations can attain exceedingly high
      densities and are not limited by natural prey availability. This has generated
      concerns that they may negatively affect prey populations, leading to calls for
      management. We enlisted cat-owners to record prey returned home to estimate
      patterns of predation by free-roaming pets in different localities within the
      town of Reading, UK and questionnaire surveys were used to quantify attitudes to
      different possible management strategies. Prey return rates were highly variable:
      only 20% of cats returned >=4 dead prey annually. Consequently, approximately 65%
      of owners received no prey in a given season, but this declined to 22% after
      eight seasons. The estimated mean predation rate was 18.3 prey cat-1 year-1 but
      this varied markedly both spatially and temporally: per capita predation rates
      declined with increasing cat density. Comparisons with estimates of the density
      of six common bird prey species indicated that cats killed numbers equivalent to
      adult density on c. 39% of occasions. Population modeling studies suggest that
      such predation rates could significantly reduce the size of local bird
      populations for common urban species. Conversely, most urban residents did not
      consider cat predation to be a significant problem. Collar-mounted anti-predation
      devices were the only management action acceptable to the majority of urban
      residents (65%), but were less acceptable to cat-owners because of perceived
      risks to their pets; only 24% of cats were fitted with such devices. Overall, cat
      predation did appear to be of sufficient magnitude to affect some prey
      populations, although further investigation of some key aspects of cat predation
      is warranted. Management of the predation behavior of urban cat populations in
      the UK is likely to be challenging and achieving this would require considerable
      engagement with cat owners.

PMID- 23173058
TI  - New alternately colored FRET sensors for simultaneous monitoring of Zn2+ in
      multiple cellular locations.
AB  - Genetically encoded sensors based on fluorescence resonance energy transfer
      (FRET) are powerful tools for reporting on ions, molecules and biochemical
      reactions in living cells. Here we describe the development of new sensors for
      Zn2+based on alternate FRET-pairs that do not involve the traditional CFP and
      YFP. Zn2+ is an essential micronutrient and plays fundamental roles in cell
      biology. Consequently there is a pressing need for robust sensors to monitor Zn2+
      levels and dynamics in cells with high spatial and temporal resolution. Here we
      develop a suite of sensors using alternate FRET pairs, including
      tSapphire/TagRFP, tSapphire/mKO, Clover/mRuby2, mOrange2/mCherry, and
      mOrange2/mKATE. These sensors were targeted to both the nucleus and cytosol and
      characterized and validated in living cells. Sensors based on the new FRET pair
      Clover/mRuby2 displayed a higher dynamic range and better signal-to-noise ratio
      than the remaining sensors tested and were optimal for monitoring changes in
      cytosolic and nuclear Zn2+. Using a green-red sensor targeted to the nucleus and
      cyan-yellow sensor targeted to either the ER, Golgi, or mitochondria, we were
      able to monitor Zn2+ uptake simultaneously in two compartments, revealing that
      nuclear Zn2+ rises quickly, whereas the ER, Golgi, and mitochondria all sequester
      Zn2+ more slowly and with a delay of 600-700 sec. Lastly, these studies provide
      the first glimpse of nuclear Zn2+ and reveal that nuclear Zn2+ is buffered at a
      higher level than cytosolic Zn2+.

PMID- 23173059
TI  - Biodiversity increases the productivity and stability of phytoplankton
      communities.
AB  - Global biodiversity losses provide an immediate impetus to elucidate the
      relationships between biodiversity, productivity and stability. In this study, we
      quantified the effects of species richness and species combination on the
      productivity and stability of phytoplankton communities subject to predation by a
      single rotifer species. We also tested one mechanism of the insurance hypothesis:
      whether large, slow-growing, potentially-defended cells would compensate for the
      loss of small, fast-growing, poorly-defended cells after predation. There were
      significant effects of species richness and species combination on the
      productivity, relative yield, and stability of phytoplankton cultures, but the
      relative importance of species richness and combination varied with the response
      variables. Species combination drove patterns of productivity, whereas species
      richness was more important for stability. Polycultures containing the most
      productive single species, Dunaliella, were consistently the most productive.
      Yet, the most species rich cultures were the most stable, having low temporal
      variability in measures of biomass. Polycultures recovered from short-term
      negative grazing effects, but this recovery was not due to the compensation of
      large, slow-growing cells for the loss of small, fast-growing cells. Instead,
      polyculture recovery was the result of reduced rotifer grazing rates and
      persisting small species within the polycultures. Therefore, although an
      insurance effect in polycultures was found, this effect was indirect and
      unrelated to grazing tolerance. We hypothesize that diverse phytoplankton
      assemblages interfered with efficient rotifer grazing and that this "interference
      effect" facilitated the recovery of the most productive species, Dunaliella. In
      summary, we demonstrate that both species composition and species richness are
      important in driving patterns of productivity and stability, respectively, and
      that stability in biodiverse communities can result from an alteration in
      consumer functioning. Our findings underscore the importance of predator-prey
      dynamics in determining the relationships between biodiversity, productivity and
      stability in producer communities.

PMID- 23173061
TI  - Impact of free delivery care on health facility delivery and insurance coverage
      in Ghana's Brong Ahafo Region.
AB  - BACKGROUND: Many sub-Saharan countries, including Ghana, have introduced policies
      to provide free medical care to pregnant women. The impact of these policies,
      particularly on access to health services among the poor, has not been evaluated
      using rigorous methods, and so the empirical basis for defending these policies
      is weak. In Ghana, a recent report also cast doubt on the current mechanism of
      delivering free care--the National Health Insurance Scheme. Longitudinal
      surveillance data from two randomized controlled trials conducted in the Brong
      Ahafo Region provided a unique opportunity to assess the impact of Ghana's
      policies. METHODS: We used time-series methods to assess the impact of Ghana's
      2005 policy on free delivery care and its 2008 policy on free national health
      insurance for pregnant women. We estimated their impacts on facility delivery and
      insurance coverage, and on socioeconomic differentials in these outcomes after
      controlling for temporal trends and seasonality. RESULTS: Facility delivery has
      been increasing significantly over time. The 2005 and 2008 policies were
      associated with significant jumps in coverage of 2.3% (p = 0.015) and 7.5%
      (p<0.001), respectively after the policies were introduced. Health insurance
      coverage also jumped significantly (17.5%, p<0.001) after the 2008 policy. The
      increases in facility delivery and insurance were greatest among the poorest,
      leading to a decline in socioeconomic inequality in both outcomes. CONCLUSION:
      Providing free care, particularly through free health insurance, has been
      effective in increasing facility delivery overall in the Brong Ahafo Region, and
      especially among the poor. This finding should be considered when evaluating the
      impact of the National Health Insurance Scheme and in supporting the continuation
      and expansion of free delivery care.

PMID- 23173062
TI  - Do young adults participate in surveys that 'go green'? Response rates to a web
      and mailed survey of weight-related health behaviors.
AB  - There is a paucity of research regarding the contextual factors that influence
      health behaviors to inform the development of programs and services for youth
      during the transition from adolescence to young adulthood. Researchers are thus
      in need of efficient strategies for surveying diverse populations of young
      adults. This study among a population-based sample of young adults aimed to 1)
      examine response to a mixed-mode survey design (web and mailed surveys) and 2)
      identify demographic correlates of response mode. Young adults who participated
      in previous study waves were invited to participate in the third wave of a 10
      year longitudinal study (Project EAT-III: 2008-2009) examining factors associated
      with weight-related behaviors. Participants were mailed invitation letters
      providing the web address and a unique password for completing the survey.
      Nonresponders were mailed three reminder invitations; the third mailing included
      the paper form, and all other mailings included a postage-paid card for
      requesting the paper form. Most completed surveys (82.1% of n=2,287) were
      returned by respondents within the first four months of fielding prior to the
      mailing which included the paper form. Nearly all of these early responders
      (92.6% of n=1,878) and 86.5% of the full respondent sample (n=1,979 of 2,287)
      completed the web form. Response to the web versus mailed paper form of the
      survey was associated with age >25 years, higher socioeconomic status, current
      employment, student status, and having no children. The combination of web and
      mailed survey modes is an effective strategy for conducting data collection in
      demographically diverse, young adult populations.

PMID- 23173060
TI  - Epithelial-mesenchymal-transition-like and TGFbeta pathways associated with
      autochthonous inflammatory melanoma development in mice.
AB  - We compared gene expression signatures of aggressive amelanotic (Amela) melanomas
      with those of slowly growing pigmented melanomas (Mela), identifying pathways
      potentially responsible for the aggressive Amela phenotype. Both tumors develop
      in mice upon conditional deletion in melanocytes of Ink4a/Arf tumor suppressor
      genes with concomitant expression of oncogene H-Ras(G12V) and a known tumor
      antigen. We previously showed that only the aggressive Amela tumors were highly
      infiltrated by leukocytes concomitant with local and systemic inflammation. We
      report that Amela tumors present a pattern of de-differentiation with reduced
      expression of genes involved in pigmentation. This correlates with reduced and
      enhanced expression, respectively, of microphthalmia-associated (Mitf) and
      Pou3f2/Brn-2 transcription factors. The reduced expression of Mitf-controlled
      melanocyte differentiation antigens also observed in some human cutaneous
      melanoma has important implications for immunotherapy protocols that generally
      target such antigens. Induced Amela tumors also express Epithelial-Mesenchymal
      Transition (EMT)-like and TGFbeta-pathway signatures. These are correlated with
      constitutive Smad3 signaling in Amela tumors and melanoma cell lines. Signatures
      of infiltrating leukocytes and some chemokines such as chemotactic cytokine
      ligand 2 (Ccl2) that contribute to leukocyte recruitment further characterize
      Amela tumors. Inhibition of the mitogen-activated protein kinase (MAPK)
      activation pathway in Amela tumor lines leads to reduced expression of EMT
      hallmark genes and inhibits both proinflammatory cytokine Ccl2 gene expression
      and Ccl2 production by the melanoma cells. These results indicate a link between
      EMT-like processes and alterations of immune functions, both being controlled by
      the MAPK pathway. They further suggest that targeting the MAPK pathway within
      tumor cells will impact tumor-intrinsic oncogenic properties as well as the
      nature of the tumor microenvironment.

PMID- 23173063
TI  - Alzheimer's disease: development of disease-modifying treatments is the challenge
      for our generation.

PMID- 23173064
TI  - Dye-binding assays for evaluation of the effects of small molecule inhibitors on
      amyloid (abeta) self-assembly.
AB  - Dye-binding assays, such as those utilizing Congo red and thioflavin T, are among
      the most widely used tools to probe the aggregation of amyloidogenic biomolecules
      and for the evaluation of small molecule inhibitors of amyloid aggregation and
      fibrillization. A number of recent reports have indicated that these dye-binding
      assays could be prone to false positive effects when assessing inhibitors'
      potential toward Abeta peptides, species involved in Alzheimer's disease.
      Specifically, this review focuses on the application of thioflavin T for
      determining the efficiency of small molecule inhibitors of Abeta aggregation and
      addresses potential reasons that might be associated with the false positive
      effects in an effort to increase reliability of dye-binding assays.

PMID- 23173065
TI  - Phosphodiesterases as therapeutic targets for Alzheimer's disease.
AB  - Alzheimer's disease (AD) is the most common form of dementia among the elderly.
      In AD patients, memory loss is accompanied by the formation of beta-amyloid
      plaques and the appearance of tau in a pathological form. Given the lack of
      effective treatments for AD, the development of new management strategies for
      these patients is critical. The continued failure to find effective therapies
      using molecules aimed at addressing the anti-beta amyloid pathology has led
      researchers to focus on other non-amyloid-based approaches to restore memory
      function. Promising non-amyloid related candidate targets include
      phosphosdiesterases (PDEs), and indeed, Rolipram, a specific PDE4 inhibitor, was
      the first compound found to effectively restore cognitive deficits in animal
      models of AD. More recently, PDE5 inhibitors have also been shown to effectively
      restore memory function. Accordingly, inhibitors of other members of the PDE
      family may also improve memory performance in AD and non-AD animal models. Hence,
      in this review, we will summarize the data supporting the use of PDE inhibitors
      as cognitive enhancers and we will discuss the possible mechanisms of action
      underlying these effects. We shall also adopt a medicinal chemistry perspective
      that leads us to propose the most promising PDE candidates on the basis of
      inhibitor selectivity, brain distribution, and mechanism of action.

PMID- 23173066
TI  - The role of molecular simulations in the development of inhibitors of amyloid
      beta-peptide aggregation for the treatment of Alzheimer's disease.
AB  - The pathogenic aggregation of the amyloid beta-peptide (Abeta) is considered a
      hallmark of the progression of Alzheimer's disease, the leading cause of senile
      dementia in the elderly and one of the principal causes of death in the United
      States. In the absence of effective therapeutics, the incidence and economic
      burden associated with the disease are expected to rise dramatically in the
      coming decades. Targeting Abeta aggregation is an attractive therapeutic
      approach, though structural insights into the nature of Abeta aggregates from
      traditional experiments are elusive, making drug design difficult. Theoretical
      methods have been used for several years to augment experimental work and drive
      progress forward in Alzheimer's drug design. In this Review, we will describe how
      two common techniques, molecular docking and molecular dynamics simulations, are
      being applied in developing small molecules as effective therapeutics against
      monomeric, oligomeric, and fibrillated forms of Abeta. Recent successes and
      important limitations will be discussed, and we conclude by providing a
      perspective on the future of this field by citing recent examples of
      sophisticated approaches used to better characterize interactions of small
      molecules with Abeta and other amyloidogenic proteins.

PMID- 23173069
TI  - Targeting selective activation of M(1) for the treatment of Alzheimer's disease:
      further chemical optimization and pharmacological characterization of the M(1)
      positive allosteric modulator ML169.
AB  - The M(1) muscarinic acetylcholine receptor is thought to play an important role
      in memory and cognition, making it a potential target for the treatment of
      Alzheimer's disease (AD) and schizophrenia. Moreover, M(1) interacts with BACE1
      and regulates its proteosomal degradation, suggesting selective M(1) activation
      could afford both palliative cognitive benefit as well as disease modification in
      AD. A key challenge in targeting the muscarinic acetylcholine receptors is
      achieving mAChR subtype selectivity. Our lab has previously reported the M(1)
      selective positive allosteric modulator ML169. Herein we describe our efforts to
      further optimize this lead compound by preparing analogue libraries and probing
      novel scaffolds. We were able to identify several analogues that possessed
      submicromolar potency, with our best example displaying an EC(50) of 310 nM. The
      new compounds maintained complete selectivity for the M(1) receptor over the
      other subtypes (M(2)-M(5)), displayed improved DMPK profiles, and potentiated the
      carbachol (CCh)-induced excitation in striatal MSNs. Selected analogues were able
      to potentiate CCh-mediated nonamyloidogenic APPsalpha release, further
      strengthening the concept that M(1) PAMs may afford a disease-modifying role in
      the treatment of AD.

PMID- 23173068
TI  - Stabilizers of neuronal and mitochondrial calcium cycling as a strategy for
      developing a medicine for Alzheimer's disease.
AB  - For the last two decades, most efforts on new drug development to treat
      Alzheimer's disease have been focused to inhibit the synthesis of amyloid beta
      (Abeta), to prevent Abeta deposition, or to clear up Abeta plaques from the brain
      of Alzheimer's disease (AD) patients. Other pathogenic mechanisms such as the
      hyperphosphorylation of the microtubular tau protein (that forms neurofibrillary
      tangles) have also been addressed as, for instance, with inhibitors of the enzyme
      glycogen synthase-3 kinase beta (GSK3beta). However, in spite of their proven
      efficacy in animal models of AD, all these compounds have so far failed in
      clinical trials done in AD patients. It seems therefore desirable to explore new
      concepts and strategies in the field of drug development for AD. We analyze here
      our hypothesis that a trifunctional chemical entity acting on the L subtype of
      voltage-dependent Ca(2+) channels (VDCCs) and on the mitochondrial Na(+)/Ca(2+)
      exchanger (MNCX), and having additional antioxidant properties, may efficiently
      delay or stop the death of vulnerable neurons in the brain of AD patients. In
      recent years, evidence has accumulated indicating that enhanced neuronal Ca(2+)
      cycling (NCC) and futile mitochondrial Ca(2+) cycling (MCC) are central stage in
      activating calpain and calcineurin, as well as the intrinsic mitochondrial
      pathway for apoptosis, leading to death of vulnerable neurons. An additional
      contributing factor to neuronal death is the excess free radical production
      linked to distortion of Ca(2+) homeostasis. We propose that an hybrid compound
      containing a dihydropyridine moiety (to block L channels and mitigate Ca(2+)
      entry) and a benzothiazepine moiety (to block the MNCX and slow down the rate of
      Ca(2+) efflux from the mitochondrial matrix into the cytosol), as well as a
      polyphenol moiety (to sequester excess free radicals) could break down the
      pathological enhanced NCC and MCC, thus delaying the initiation of apoptosis and
      the death of vulnerable neurons. In so doing, such a trifunctional compound could
      eventually become a neuroprotective medicine capable of delaying disease
      progression in AD patients.

PMID- 23173067
TI  - Recent advances in the design, synthesis, and biological evaluation of selective
      DYRK1A inhibitors: a new avenue for a disease modifying treatment of Alzheimer's?
AB  - With 24.3 million people affected in 2005 and an estimated rise to 42.3 million
      in 2020, dementia is currently a leading unmet medical need and costly burden on
      public health. Seventy percent of these cases have been attributed to Alzheimer's
      disease (AD), a neurodegenerative pathology whose most evident symptom is a
      progressive decline in cognitive functions. Dual specificity tyrosine
      phosphorylation regulated kinase-1A (DYRK1A) is important in neuronal development
      and plays a variety of functional roles within the adult central nervous system.
      The DYRK1A gene is located within the Down syndrome critical region (DSCR) on
      human chromosome 21 and current research suggests that overexpression of DYRK1A
      may be a significant factor leading to cognitive deficits in people with
      Alzheimer's disease (AD) and Down syndrome (DS). Currently, treatment options for
      cognitive deficiencies associated with Down syndrome, as well as Alzheimer's
      disease, are extremely limited and represent a major unmet therapeutic need.
      Small molecule inhibition of DYRK1A activity in the brain may provide an avenue
      for pharmaceutical intervention of mental impairment associated with AD and other
      neurodegenerative diseases. We herein review the current state of the art in the
      development of DYRK1A inhibitors.

PMID- 23173070
TI  - Facile methodology for monitoring amyloid-beta fibrillization.
AB  - Amyloid-beta (Abeta) is a peptide fragment that is prone to aggregate into large
      fibrils under physiological conditions. Many techniques have been developed to
      quickly monitor the transition from a primarily monomeric peptide into fibrils.
      Here we propose a novel method for both incubating and monitoring changes in
      Abeta aggregation by using modified NMR tubes, a microtube thermoshaker, and a
      fluorescence or UV-vis spectrometer. These NMR tubes are thin and cylindrical,
      which allows efficient heat transfer and orbital shaking. Our results demonstrate
      that our technique is both reliable and expedient when tracking Abeta
      fibrillization using fluorescence or turbidity assays, which presents an
      alternative for laboratories without specialized equipment for incubating
      peptide.

PMID- 23173071
TI  - Familial Alzheimer's disease mutations differentially alter amyloid beta-protein
      oligomerization.
AB  - Although most cases of Alzheimer's disease (AD) are sporadic, ~5% of cases are
      genetic in origin. These cases, known as familial Alzheimer's disease (FAD), are
      caused by mutations that alter the rate of production or the primary structure of
      the amyloid beta-protein (Abeta). Changes in the primary structure of Abeta alter
      the peptide's assembly and toxic activity. Recently, a primary working hypothesis
      for AD has evolved where causation has been attributed to early, soluble peptide
      oligomer states. Here we posit that both experimental and pathological
      differences between FAD-related mutants and wild-type Abeta could be reflected in
      the early oligomer distributions of these peptides. We use ion mobility-based
      mass spectrometry to probe the structure and early aggregation states of three
      mutant forms of Abeta40 and Abeta42: Tottori (D7N), Flemish (A21G), and Arctic
      (E22G). Our results indicate that the FAD-related amino acid substitutions have
      no noticeable effect on Abeta monomer cross section, indicating there are no
      major structural changes in the monomers. However, we observe significant changes
      to the aggregation states populated by the various Abeta mutants, indicating that
      structural changes present in the monomers are reflected in the oligomers.
      Moreover, the early oligomer distributions differ for each mutant, suggesting a
      possible structural basis for the varied pathogenesis of different forms of FAD.

PMID- 23173072
TI  - An N-heterocyclic amine chelate capable of antioxidant capacity and amyloid
      disaggregation.
AB  - Alzheimer's disease is a neurodegenerative disorder characterized by the
      development of intracellular neurofibrillary tangles, deposition of extracellular
      amyloid beta (Abeta) plaques, along with a disruption of transition metal ion
      homeostasis in conjunction with oxidative stress. Spectroscopic, transmission
      electron microscopy, and scanning electron microscopy imaging studies show that 1
      (pyclen) is capable of both preventing and disrupting Cu(2+) induced AB(1-40)
      aggregation. The pyridine backbone of 1 engenders antioxidant capacity, as shown
      by cellular DCFH-DA (dichlorodihydrofluorescein diacetate) assay in comparison to
      other N-heterocyclic amines lacking this aromatic feature. Finally, 1 prevents
      cell death induced by oxidative stress as shown by the Calcein AM assay. The
      results are supported using density functional theory studies which show that the
      pyridine backbone is responsible for the antioxidant capacity observed.

PMID- 23173073
TI  - Brain-penetrant tetrahydronaphthalene thromboxane A2-prostanoid (TP) receptor
      antagonists as prototype therapeutics for Alzheimer's disease.
AB  - A hallmark pathological feature of the Alzheimer's disease (AD) brain is the
      presence of senile plaques, which comprise amyloid beta (Abeta) peptides that are
      derived from the amyloid precursor protein (APP). The plaque-containing AD brain
      is thought to be under oxidative stress, as evidenced by increased lipid
      oxidation products that include isoprostane-F2alphaIII (iPF2alphaIII).
      IPF2alphaIII can bind to and activate the thromboxane A2-prostanoid (TP)
      receptor, and TP receptor activation causes increased Abeta production through
      enhancement of APP mRNA stability. Moreover, TP receptor antagonists have been
      shown to block iPF2alphaIII-induced increases of Abeta secretion. Thus, the TP
      receptor may be a potential drug target for AD therapy. However, here we show
      that existing TP receptor antagonists have poor blood-brain barrier (BBB)
      permeability, likely due to the presence of a carboxylic acid moiety that is
      believed to be important for receptor interaction, but which may hamper passive
      diffusion across the BBB. We now report selected analogues of a known
      tetrahydronaphthalene TP receptor antagonist, wherein the carboxylic acid moiety
      has been replaced by heterocyclic bioisosteres. These heterocyclic analogues
      retained relatively high affinity for the mouse and human TP receptors, and,
      unlike the parent carboxylic acid compound, several examples freely diffused
      across the BBB into the brain upon administration to mice. These results reveal
      that brain-penetrant tetrahydronaphthalene TP receptor antagonists can be
      developed by substituting the carboxylic acid moiety with a suitable nonacidic
      bioisostere. Compounds of this type hold promise as potential lead structures to
      develop drug candidates for the treatment of AD.

PMID- 23173074
TI  - Amyloid beta-peptide 25-35 self-assembly and its inhibition: a model
      undecapeptide system to gain atomistic and secondary structure details of the
      Alzheimer's disease process and treatment.
AB  - Combined results of theoretical molecular dynamic simulations and in vitro
      spectroscopic (circular dichroism and fluorescence) studies are presented,
      providing the atomistic and secondary structure details of the process by which a
      selected small molecule may destabilize the beta-sheet ordered "amyloid"
      oligomers formed by the model undecapeptide of amyloid beta-peptide 25-35
      [Abeta(25-35)]. Abeta(25-35) was chosen because it is the shortest fragment
      capable of forming large beta-sheet fibrils and retaining the toxicity of the
      full length Abeta(1-40/42) peptides. The conformational transition, that leads to
      the formation of beta-sheet fibrils from soluble unordered structures, was found
      to depend on the environmental conditions, whereas the presence of myricetin
      destabilizes the self-assembly and antagonizes this conformational shift. In
      parallel, we analyzed several molecular dynamics trajectories describing the
      evolution of five monomer fragments, without inhibitor as well as in the presence
      of myricetin. Other well-known inhibitors (curcumin and (-)-tetracycline), found
      to be stronger and weaker Abeta(1-42) aggregation inhibitors, respectively, were
      also studied. The combined in vitro and theoretical studies of the Abeta(25-35)
      self-assembly and its inhibition contribute to understanding the mechanism of
      action of well-known inhibitors and the peptide amino acid residues involved in
      the interaction leading to a rational drug design of more potent new molecules
      able to antagonize the self-assembly process.

PMID- 23173075
TI  - Glycogen synthase kinase 3 inhibition promotes adult hippocampal neurogenesis in
      vitro and in vivo.
AB  - Glycogen synthase kinase-3 (GSK-3) is a serine/threonine kinase originally
      identified as a regulator of glycogen metabolism but it also plays a pivotal role
      in numerous cellular functions, including differentiation, cell cycle regulation,
      and proliferation. The dentate gyrus of the hippocampus, together with the
      subventricular zone of the lateral ventricles, is one of the regions in which
      neurogenesis takes place in the adult brain. Here, using a chemical genetic
      approach that involves the use of several diverse inhibitors of GSK-3 as
      pharmacological tools, we show that inhibition of GSK-3 induces proliferation,
      migration, and differentiation of neural stem cells toward a neuronal phenotype
      in in vitro studies. Also, we demonstrate that inhibition of GSK-3 with the small
      molecule NP03112, called tideglusib, induces neurogenesis in the dentate gyrus of
      the hippocampus of adult rats. Taken together, our results suggest that GSK-3
      should be considered as a new target molecule for modulating the production and
      integration of new neurons in the hippocampus as a treatment for
      neurodegenerative diseases or brain injury and, consequently, its inhibitors may
      represent new potential therapeutic drugs in neuroregenerative medicine.

PMID- 23173076
TI  - Synapse-binding subpopulations of Abeta oligomers sensitive to peptide assembly
      blockers and scFv antibodies.
AB  - Amyloid beta42 self-assembly is complex, with multiple pathways leading to large
      insoluble fibrils or soluble oligomers. Oligomers are now regarded as most
      germane to Alzheimer's pathogenesis. We have investigated the hypothesis that
      oligomer formation itself occurs through alternative pathways, with some leading
      to synapse-binding toxins. Immediately after adding synthetic peptide to buffer,
      solutions of Abeta42 were separated by a 50 kDa filter and fractions assessed by
      SDS-PAGE silver stain, Western blot, immunoprecipitation, and capacity for
      synaptic binding. Abeta42 rapidly assembled into aqueous-stable oligomers, with
      similar protein abundance in small (<50 kDa) and large (>50 kDa) oligomer
      fractions. Initially, both fractions were SDS-labile and resolved into tetramers,
      trimers, and monomers by SDS-PAGE. Upon continued incubation, the larger
      oligomers developed a small population of SDS-stable 10-16mers, and the smaller
      oligomers generated gel-impermeant complexes. The two fractions associated
      differently with neurons, with prominent synaptic binding limited to larger
      oligomers. Even within the family of larger oligomers, synaptic binding was
      associated with only a subset of these species, as a new scFv antibody (NUsc1)
      immunoprecipitated only a small portion of the oligomers while eliminating
      synaptic binding. Interestingly, low doses of the peptide KLVFFA blocked assembly
      of the 10-16mers, and this result was associated with loss of the smaller
      clusters of oligomers observed at synaptic sites. What distinguishes these
      smaller clusters from the unaffected larger clusters is not yet known. Results
      indicate that distinct species of Abeta oligomers are generated by alternative
      assembly pathways and that synapse-binding subpopulations of Abeta oligomers
      could be specifically targeted for Alzheimer's therapeutics.

PMID- 23173077
TI  - The modelling cycle for collective animal behaviour.
AB  - Collective animal behaviour is the study of how interactions between individuals
      produce group level patterns, and why these interactions have evolved. This study
      has proved itself uniquely interdisciplinary, involving physicists,
      mathematicians, engineers as well as biologists. Almost all experimental work in
      this area is related directly or indirectly to mathematical models, with regular
      movement back and forth between models, experimental data and statistical
      fitting. In this paper, we describe how the modelling cycle works in the study of
      collective animal behaviour. We classify studies as addressing questions at
      different levels or linking different levels, i.e. as local, local to global,
      global to local or global. We also describe three distinct approaches-theory
      driven, data-driven and model selection-to these questions. We show, with
      reference to our own research on species across different taxa, how we move
      between these different levels of description and how these various approaches
      can be applied to link levels together.

PMID- 23173078
TI  - Solitons beyond binary: possibility of fibre-optic transmission of two bits per
      clock period.
AB  - Optical telecommunication employs light pulses travelling down optical fibres; in
      a binary format logical Ones and Zeroes are represented by the presence or
      absence of a light pulse in a given time slot, respectively. The fibre's data
      carrying capacity must keep up with increasing demand, but for binary coding it
      now approaches its limit. Alternative coding schemes beyond binary are currently
      hotly debated; the challenge is to mitigate detrimental effects from the fibre's
      nonlinearity. Here we provide proof-of-principle that coding with solitons and
      soliton molecules allows to encode two bits of data per clock period. Solitons do
      not suffer from nonlinearity, rather, they rely on it; this endows them with
      greater robustness. However, they are universally considered to be restricted to
      binary coding. With that notion now refuted, it is warranted to rethink future
      systems.

PMID- 23173080
TI  - Estimation of the Frequency of Intravenous Drug Users in Hamadan City, Iran,
      Using the Capture-recapture Method.
AB  - OBJECTIVES: The number of illicit drug users is prone to underestimation. This
      study aimed to use the capture-recapture method as a statistical procedure for
      measuring the prevalence of intravenous drug users (IDUs) by estimating the
      number of unknown IDUs not registered by any of the registry centers. METHODS:
      This study was conducted in Hamadan City, the west of Iran, in 2012. Three
      incomplete data sources of IDUs, with partial overlapping data, were assessed
      including: (a) Volunteer Counseling and Testing Centers (VCTCs); (b) Drop in
      Centers (DICs); and (c) Outreach Teams (ORTs). A log-linear model was applied for
      the analysis of three-sample capture-recapture results. Two information criteria
      were used for model selection including Akaike's Information Criterion and the
      Bayesian Information Criterion. RESULTS: Out of 1,478 IDUs registered by three
      centers, 48% were identified by VCTCs, 32% by DICs, and 20% by ORTs. After
      exclusion of duplicates, 1,369 IDUs remained. According to our findings, there
      were 9,964 (95% CI, 6,088 to 17,636) IDUs not identified by any of the centers.
      Hence, the real number of IDUs is expected to be 11,333. Based on these findings,
      the overall completeness of the three data sources was around 12% (95% CI, 7% to
      18%). CONCLUSION: There was a considerable number of IDUs not identified by any
      of the centers. Although the capture-recapture method is a useful and practical
      approach for estimating unknown populations, due to the assumptions and
      limitations of the method, the results must be interpreted with caution.

PMID- 23173079
TI  - Bacteriophytochrome controls carotenoid-independent response to photodynamic
      stress in a non-photosynthetic rhizobacterium, Azospirillum brasilense Sp7.
AB  - Ever since the discovery of the role of bacteriophytochrome (BphP) in inducing
      carotenoid synthesis in Deinococcus radiodurans in response to light the role of
      BphPs in other non-photosynthetic bacteria is not clear yet. Azospirillum
      brasilense, a non-photosynthetic rhizobacterium, harbours a pair of BphPs out of
      which AbBphP1 is a homolog of AtBphP1 of Agrobacterium tumefaciens. By
      overexpression, purification, biochemical and spectral characterization we have
      shown that AbBphP1 is a photochromic bacteriophytochrome. Phenotypic study of the
      DeltaAbBphP1 mutant showed that it is required for the survival of A. brasilense
      on minimal medium under red light. The mutant also showed reduced chemotaxis
      towards dicarboxylates and increased sensitivity to the photooxidative stress.
      Unlike D. radiodurans, AbBphP1 was not involved in controlling carotenoid
      synthesis. Proteome analysis of the DeltaAbBphP1 indicated that AbBphP1 is
      involved in inducing a cellular response that enables A. brasilense in
      regenerating proteins that might be damaged due to photodynamic stress.

PMID- 23173081
TI  - Mapping the genetic basis of symbiotic variation in legume-rhizobium interactions
      in Medicago truncatula.
AB  - Mutualisms are known to be genetically variable, where the genotypes differ in
      the fitness benefits they gain from the interaction. To date, little is known
      about the loci that underlie such genetic variation in fitness or whether the
      loci influencing fitness are partner specific, and depend on the genotype of the
      interaction partner. In the legume-rhizobium mutualism, one set of potential
      candidate genes that may influence the fitness benefits of the symbiosis are the
      plant genes involved in the initiation of the signaling pathway between the two
      partners. Here we performed quantitative trait loci (QTL) mapping in Medicago
      truncatula in two different rhizobium strain treatments to locate regions of the
      genome influencing plant traits, assess whether such regions are dependent on the
      genotype of the rhizobial mutualist (QTL * rhizobium strain), and evaluate the
      contribution of sequence variation at known symbiosis signaling genes. Two of the
      symbiotic signaling genes, NFP and DMI3, colocalized with two QTL affecting
      average fruit weight and leaf number, suggesting that natural variation in
      nodulation genes may potentially influence plant fitness. In both rhizobium
      strain treatments, there were QTL that influenced multiple traits, indicative of
      either tight linkage between loci or pleiotropy, including one QTL with opposing
      effects on growth and reproduction. There was no evidence for QTL * rhizobium
      strain or genotype * genotype interactions, suggesting either that such
      interactions are due to small-effect loci or that more genotype-genotype
      combinations need to be tested in future mapping studies.

PMID- 23173083
TI  - Genetic analysis of vertebral regionalization and number in medaka (Oryzias
      latipes) inbred lines.
AB  - Vertebral number is the most variable trait among vertebrates. In addition to the
      vertebral number, the ratio of abdominal to caudal vertebrae is a variable trait.
      The vertebral number and the ratio of abdominal to caudal vertebrae contribute to
      vertebrate diversity. It is very interesting to know how to determine the
      vertebral number and the ratio of abdominal to caudal vertebrae. In this study,
      we identify differences in the vertebral number and the ratio of abdominal
      vertebrae to vertebral number between two inbred lines of medaka, namely, Hd
      rRII1 and Kaga. To identify the genetic factor of those differences, we performed
      quantitative trait locus (QTL) analysis for vertebral number and the ratio of
      abdominal vertebrae to vertebral number using 200 F(2) fish. Our results show a
      suggestive QTL of the ratio of abdominal vertebrae to vertebral number on
      chromosome 15, and five QTL of vertebral number on chromosomes 1, 10, 11, 17, and
      23. The QTL on chromosome 15 contains hoxDb cluster genes. The QTL of vertebral
      number include some genes related to the segmentation clock and axial elongation.
      In addition, we show that the difference in vertebral number between two inbred
      lines is derived from differences in the anteroposterior length of somites. Our
      results emphasize that the developmental process should be considered in genetic
      analyses for vertebral number.

PMID- 23173082
TI  - Gal4-based enhancer-trapping in the malaria mosquito Anopheles stephensi.
AB  - Transposon-based forward and reverse genetic technologies will contribute greatly
      to ongoing efforts to study mosquito functional genomics. A piggyBac transposon
      based enhancer-trap system was developed that functions efficiently in the human
      malaria vector, Anopheles stephensi. The system consists of six transgenic lines
      of Anopheles stephensi, each with a single piggyBac-Gal4 element in a unique
      genomic location; six lines with a single piggyBac-UAStdTomato element; and two
      lines, each with a single Minos element containing the piggyBac-transposase gene
      under the regulatory control of the hsp70 promoter from Drosophila melanogaster.
      Enhancer detection depended upon the efficient remobilization of piggyBac-Gal4
      transposons, which contain the yeast transcription factor gene Gal4 under the
      regulatory control of a basal promoter. Gal4 expression was detected through the
      expression of the fluorescent protein gene tdTomato under the regulatory control
      of a promoter with Gal4-binding UAS elements. From five genetic screens for
      larval- and adult-specific enhancers, 314 progeny were recovered from 24,250
      total progeny (1.3%) with unique patterns of tdTomato expression arising from the
      influence of an enhancer. The frequency of piggyBac remobilization and enhancer
      detection was 2.5- to 3-fold higher in female germ lines compared with male germ
      lines. A small collection of enhancer-trap lines are described in which Gal4
      expression occurred in adult female salivary glands, midgut, and fat body, either
      singly or in combination. These three tissues play critical roles during the
      infection of Anopheles stephensi by malaria-causing Plasmodium parasites. This
      system and the lines generated using it will be valuable resources to ongoing
      mosquito functional genomics efforts.

PMID- 23173084
TI  - A window into domain amplification through Piccolo in teleost fish.
AB  - I describe and characterize the extensive amplification of the zinc finger domain
      of Piccolo selectively in teleost fish. Piccolo and Bassoon are partially
      functionally redundant and play roles in regulating the pool of neurotransmitter
      filled synaptic vesicles present at synapses. In mice, each protein contains two
      N-terminal zinc finger domains that have been implicated in interacting with
      synaptic vesicles. In all teleosts examined, both the Bassoon and Piccolo genes
      are duplicated. Both teleost bassoon genes and one piccolo gene show very similar
      domain structure and intron-exon organization to their mouse homologs. In
      contrast, in piccolo b a single exon that encodes a zinc finger domain is
      amplified 8 to 16 times in different teleost species. Analysis of the amplified
      exons suggests they were added and/or deleted from the gene as individual exons
      in rare events that are likely the result of unequal crossovers between
      homologous sequences. Surprisingly, the structure of the repeats from cod and
      zebrafish suggest that amplification of this exon has occurred independently
      multiple times in the teleost lineage. Based on the structure of the exons, I
      propose a model in which selection for high sequence similarity at the 5' and 3'
      ends of the exon drives amplification of the repeats and diversity in repeat
      length likely promotes the stability of the repeated exons by minimizing the
      likelihood of mispairing of adjacent repeat sequences. Further analysis of
      piccolo b in teleosts should provide a window through which to examine the
      process of domain amplification.

PMID- 23173085
TI  - Escherichia coli lacking RpoS are rare in natural populations of non-pathogens.
AB  - The alternative sigma factor RpoS controls a large regulon that allows E. coli to
      respond to a variety of stresses. Mutations in rpoS can increase rates of
      nutrient acquisition at the cost of a decrease in stress resistance. These kinds
      of mutations evolve rapidly under certain laboratory conditions where nutrient
      acquisition is especially challenging. The frequency of strains lacking RpoS in
      natural populations of E. coli is less clear. Such strains have been found at
      frequencies over 20% in some collections of wild isolates. However, laboratory
      handling can select for RpoS-null strains and may have affected some of these
      strain collections. Other studies have included an unknown diversity of strains
      or only used a phenotypic proxy as a measure of RpoS levels. We directly measured
      RpoS levels in a collection of E. coli that includes the full diversity of the
      species and that was handled in a manner to minimize the potential for laboratory
      evolution. We found that only 2% of strains produce no functional RpoS.
      Comparison of these strains in multiple labs shows that these rpoS mutations
      occurred in the laboratory. Earlier studies reporting much higher levels of RpoS
      polymorphism may reflect the storage history of the strains in laboratories
      rather than true frequency of such strains in natural populations.

PMID- 23173087
TI  - SAGA complex components and acetate repression in Aspergillus nidulans.
AB  - Alongside the well-established carbon catabolite repression by glucose and other
      sugars, acetate causes repression in Aspergillus nidulans. Mutations in creA,
      encoding the transcriptional repressor involved in glucose repression, also
      affect acetate repression, but mutations in creB or creC, encoding components of
      a deubiquitination system, do not. To understand the effects of acetate, we used
      a mutational screen that was similar to screens that uncovered mutations in creA,
      creB, and creC, except that glucose was replaced by acetate to identify mutations
      that were affected for repression by acetate but not by glucose. We uncovered
      mutations in acdX, homologous to the yeast SAGA component gene SPT8, which in
      growth tests showed derepression for acetate repression but not for glucose
      repression. We also made mutations in sptC, homologous to the yeast SAGA
      component gene SPT3, which showed a similar phenotype. We found that acetate
      repression is complex, and analysis of facA mutations (lacking acetyl CoA
      synthetase) indicates that acetate metabolism is required for repression of some
      systems (proline metabolism) but not for others (acetamide metabolism). Although
      plate tests indicated that acdX- and sptC-null mutations led to derepressed
      alcohol dehydrogenase activity, reverse-transcription quantitative real-time
      polymerase chain reaction showed no derepression of alcA or aldA but rather
      elevated induced levels. Our results indicate that acetate repression is due to
      repression via CreA together with metabolic changes rather than due to an
      independent regulatory control mechanism.

PMID- 23173086
TI  - Identification of genes required for alternative oxidase production in the
      Neurospora crassa gene knockout library.
AB  - The alternative oxidase (AOX) of Neurospora crassa transfers electrons from
      ubiquinol to oxygen. The enzyme is not expressed under normal conditions.
      However, when the function of the standard electron transport chain is
      compromised, AOX is induced, providing cells with a means to continue respiration
      and growth. Induction of the enzyme represents a form of retrograde regulation
      because AOX is encoded by a nuclear gene that responds to signals produced from
      inefficiently functioning mitochondria. To identify genes required for AOX
      expression, we have screened the N. crassa gene knockout library for strains that
      are unable to grow in the presence of antimycin A, an inhibitor of complex III of
      the standard electron transport chain. From the 7800 strains containing knockouts
      of different genes, we identified 62 strains that have reduced levels of AOX when
      grown under conditions known to induce the enzyme. Some strains have virtually no
      AOX, whereas others have only a slight reduction of the protein. A broad range of
      seemingly unrelated functions are represented in the knockouts. For example, we
      identified transcription factors, kinases, the mitochondrial import receptor
      Tom70, three subunits of the COP9 signalosome, a monothiol glutaredoxin, and
      several hypothetical proteins as being required for wild-type levels of AOX
      production. Our results suggest that defects in many signaling or metabolic
      pathways have a negative effect on AOX expression and imply that complex systems
      control production of the enzyme.

PMID- 23173088
TI  - A germline clone screen on the X chromosome reveals novel meiotic mutants in
      Drosophila melanogaster.
AB  - In an effort to isolate novel meiotic mutants that are severely defective in
      chromosome segregation and/or exchange, we employed a germline clone screen of
      the X chromosome of Drosophila melanogaster. We screened over 120,000 EMS
      mutagenized chromosomes and isolated 19 mutants, which comprised nine
      complementation groups. Four of these complementation groups mapped to known
      meiotic genes, including mei-217, mei-218, mei-9, and nod. Importantly, we have
      identified two novel complementation groups with strong meiotic phenotypes, as
      assayed by X chromosome nondisjunction. One complementation group is defined by
      three alleles, and the second novel complementation group is defined by a single
      allele. All 19 mutants are homozygous viable, fertile, and fully recessive. Of
      the 9 mutants that have been molecularly characterized, 5 are canonical EMS
      induced transitions, and the remaining 4 are transversions. In sum, we have
      identified two new genes that are defined by novel meiotic mutants, in addition
      to isolating new alleles of mei-217, mei-218, mei-9, and nod.

PMID- 23173089
TI  - On the role of PDZ domain-encoding genes in Drosophila border cell migration.
AB  - Cells often move as collective groups during normal embryonic development and
      wound healing, although the mechanisms governing this type of migration are
      poorly understood. The Drosophila melanogaster border cells migrate as a cluster
      during late oogenesis and serve as a powerful in vivo genetic model for
      collective cell migration. To discover new genes that participate in border cell
      migration, 64 out of 66 genes that encode PDZ domain-containing proteins were
      systematically targeted by in vivo RNAi knockdown. The PDZ domain is one of the
      largest families of protein-protein interaction domains found in eukaryotes.
      Proteins that contain PDZ domains participate in a variety of biological
      processes, including signal transduction and establishment of epithelial apical
      basal polarity. Targeting PDZ proteins effectively assesses a larger number of
      genes via the protein complexes and pathways through which these proteins
      function. par-6, a known regulator of border cell migration, was a positive hit
      and thus validated the approach. Knockdown of 14 PDZ domain genes disrupted
      migration with multiple RNAi lines. The candidate genes have diverse predicted
      cellular functions and are anticipated to provide new insights into the
      mechanisms that control border cell movement. As a test of this concept, two
      genes that disrupted migration were characterized in more detail: big bang and
      the Dlg5 homolog CG6509. We present evidence that Big bang regulates JAK/STAT
      signaling, whereas Dlg5/CG6509 maintains cluster cohesion. Moreover, these
      results demonstrate that targeting a selected class of genes by RNAi can uncover
      novel regulators of collective cell migration.

PMID- 23173090
TI  - A forward genetic screen identifies eukaryotic translation initiation factor 3,
      subunit H (eIF3h), as an enhancer of variegation in the mouse.
AB  - We have used a forward genetic screen to identify genes required for transgene
      silencing in the mouse. Previously these genes were found using candidate-based
      sequencing, a slow and labor-intensive process. Recently, whole-exome deep
      sequencing has accelerated our ability to find the causative point mutations,
      resulting in the discovery of novel and sometimes unexpected genes. Here we
      report the identification of translation initiation factor 3, subunit H (eIF3h)
      in two modifier of murine metastable epialleles (Mommes) lines. Mice carrying
      mutations in this gene have not been reported previously, and a possible
      involvement of eIF3h in transcription or epigenetic regulation has not been
      considered.

PMID- 23173091
TI  - Maintaining sufficient nanos is a critical function for polar granule component
      in the specification of primordial germ cells.
AB  - Primordial germ cells (PGC) are the precursors of germline stem cells. In
      Drosophila, PGC specification is thought to require transcriptional quiescence
      and three genes, polar granule component (pgc), nanos (nos), and germ cell less
      (gcl) function to downregulate Pol II transcription. While it is not understood
      how nos or gcl represses transcription, pgc does so by inhibiting the
      transcription elongation factor b (P-TEFb), which is responsible for
      phosphorylating Ser2 residues in the heptad repeat of the C-terminal domain (CTD)
      of the largest Pol II subunit. In the studies reported here, we demonstrate that
      nos are a critical regulatory target of pgc. We show that a substantial fraction
      of the PGCs in pgc embryos have greatly reduced levels of Nos protein and exhibit
      phenotypes characteristic of nos PGCs. Lastly, restoring germ cell-specific
      expression of Nos is sufficient to ameliorate the pgc phenotype.

PMID- 23173092
TI  - Shrinkage estimation of the realized relationship matrix.
AB  - The additive relationship matrix plays an important role in mixed model
      prediction of breeding values. For genotype matrix X (loci in columns), the
      product XX' is widely used as a realized relationship matrix, but the scaling of
      this matrix is ambiguous. Our first objective was to derive a proper scaling such
      that the mean diagonal element equals 1+f, where f is the inbreeding coefficient
      of the current population. The result is a formula involving the covariance
      matrix for sampling genomic loci, which must be estimated with markers. Our
      second objective was to investigate whether shrinkage estimation of this
      covariance matrix can improve the accuracy of breeding value (GEBV) predictions
      with low-density markers. Using an analytical formula for shrinkage intensity
      that is optimal with respect to mean-squared error, simulations revealed that
      shrinkage can significantly increase GEBV accuracy in unstructured populations,
      but only for phenotyped lines; there was no benefit for unphenotyped lines. The
      accuracy gain from shrinkage increased with heritability, but at high
      heritability (> 0.6) this benefit was irrelevant because phenotypic accuracy was
      comparable. These trends were confirmed in a commercial pig population with
      progeny-test-estimated breeding values. For an anonymous trait where phenotypic
      accuracy was 0.58, shrinkage increased the average GEBV accuracy from 0.56 to
      0.62 (SE < 0.00) when using random sets of 384 markers from a 60K array. We
      conclude that when moderate-accuracy phenotypes and low-density markers are
      available for the candidates of genomic selection, shrinkage estimation of the
      relationship matrix can improve genetic gain.

PMID- 23173094
TI  - Effectiveness of genomic prediction of maize hybrid performance in different
      breeding populations and environments.
AB  - Genomic prediction is expected to considerably increase genetic gains by
      increasing selection intensity and accelerating the breeding cycle. In this
      study, marker effects estimated in 255 diverse maize (Zea mays L.) hybrids were
      used to predict grain yield, anthesis date, and anthesis-silking interval within
      the diversity panel and testcross progenies of 30 F(2)-derived lines from each of
      five populations. Although up to 25% of the genetic variance could be explained
      by cross validation within the diversity panel, the prediction of testcross
      performance of F(2)-derived lines using marker effects estimated in the diversity
      panel was on average zero. Hybrids in the diversity panel could be grouped into
      eight breeding populations differing in mean performance. When performance was
      predicted separately for each breeding population on the basis of marker effects
      estimated in the other populations, predictive ability was low (i.e., 0.12 for
      grain yield). These results suggest that prediction resulted mostly from
      differences in mean performance of the breeding populations and less from the
      relationship between the training and validation sets or linkage disequilibrium
      with causal variants underlying the predicted traits. Potential uses for genomic
      prediction in maize hybrid breeding are discussed emphasizing the need of (1) a
      clear definition of the breeding scenario in which genomic prediction should be
      applied (i.e., prediction among or within populations), (2) a detailed analysis
      of the population structure before performing cross validation, and (3) larger
      training sets with strong genetic relationship to the validation set.

PMID- 23173093
TI  - large-scale screening for targeted knockouts in the Caenorhabditis elegans
      genome.
AB  - The nematode Caenorhabditis elegans is a powerful model system to study
      contemporary biological problems. This system would be even more useful if we had
      mutations in all the genes of this multicellular metazoan. The combined efforts
      of the C. elegans Deletion Mutant Consortium and individuals within the worm
      community are moving us ever closer to this goal. At present, of the 20,377
      protein-coding genes in this organism, 6764 genes with associated molecular
      lesions are either deletions or null mutations (WormBase WS220). Our three
      laboratories have contributed the majority of mutated genes, 6841 mutations in
      6013 genes. The principal method we used to detect deletion mutations in the
      nematode utilizes polymerase chain reaction (PCR). More recently, we have used
      array comparative genome hybridization (aCGH) to detect deletions across the
      entire coding part of the genome and massively parallel short-read sequencing to
      identify nonsense, splicing, and missense defects in open reading frames. As
      deletion strains can be frozen and then thawed when needed, these strains will be
      an enduring community resource. Our combined molecular screening strategies have
      improved the overall throughput of our gene-knockout facilities and have
      broadened the types of mutations that we and others can identify. These multiple
      strategies should enable us to eventually identify a mutation in every gene in
      this multicellular organism. This knowledge will usher in a new age of metazoan
      genetics in which the contribution to any biological process can be assessed for
      all genes.

PMID- 23173095
TI  - Identification of gene expression changes associated with long-term memory of
      courtship rejection in Drosophila males.
AB  - Long-term memory formation in Drosophila melanogaster is an important neuronal
      function shaping the insect's behavioral repertoire by allowing an individual to
      modify behaviors on the basis of previous experiences. In conditioned courtship
      or courtship suppression, male flies that have been repeatedly rejected by mated
      females during courtship advances are less likely than naive males to
      subsequently court another mated female. This long-term courtship suppression can
      last for several days after the initial rejection period. Although genes with
      known functions in many associative learning paradigms, including those that
      function in cyclic AMP signaling and RNA translocation, have been identified as
      playing critical roles in long-term conditioned courtship, it is clear that
      additional mechanisms also contribute. We have used RNA sequencing to identify
      differentially expressed genes and transcript isoforms between naive males and
      males subjected to courtship-conditioning regimens that are sufficient for
      inducing long-term courtship suppression. Transcriptome analyses 24 hours after
      the training regimens revealed differentially expressed genes and transcript
      isoforms with predicted and known functions in nervous system development,
      chromatin biology, translation, cytoskeletal dynamics, and transcriptional
      regulation. A much larger number of differentially expressed transcript isoforms
      were identified, including genes previously implicated in associative memory and
      neuronal development, including fruitless, that may play functional roles in
      learning during courtship conditioning. Our results shed light on the complexity
      of the genetics that underlies this behavioral plasticity and reveal several new
      potential areas of inquiry for future studies.

PMID- 23173096
TI  - NANOGP8: evolution of a human-specific retro-oncogene.
AB  - NANOGP8 is a human (Homo sapiens) retrogene, expressed predominantly in cancer
      cells where its protein product is tumorigenic. It arose through
      retrotransposition from its parent gene, NANOG, which is expressed predominantly
      in embryonic stem cells. Based on identification of fixed and polymorphic
      variants in a genetically diverse set of human NANOG and NANOGP8 sequences, we
      estimated the evolutionary origin of NANOGP8 at approximately 0.9 to 2.5 million
      years ago, more recent than previously estimated. We also discovered that NANOGP8
      arose from a derived variant allele of NANOG containing a 22-nucleotide pair
      deletion in the 3' UTR, which has remained polymorphic in modern humans. Evidence
      from our experiments indicates that NANOGP8 is fixed in modern humans even though
      its parent allele is polymorphic. The presence of NANOGP8-specific sequences in
      Neanderthal reads provided definitive evidence that NANOGP8 is also present in
      the Neanderthal genome. Some variants between the reference sequences of NANOG
      and NANOGP8 utilized in cancer research to distinguish RT-PCR products are
      polymorphic within NANOG or NANOGP8 and thus are not universally reliable as
      distinguishing features. NANOGP8 was inserted in reverse orientation into the LTR
      region of an SVA retroelement that arose in a human-chimpanzee-gorilla common
      ancestor after divergence of the orangutan ancestral lineage. Transcription
      factor binding sites within and beyond this LTR may promote expression of NANOGP8
      in cancer cells, although current evidence is inferential. The fact that NANOGP8
      is a human-specific retro-oncogene may partially explain the higher genetic
      predisposition for cancer in humans compared with other primates.

PMID- 23173097
TI  - Evidence for autoregulation and cell signaling pathway regulation from genome
      wide binding of the Drosophila retinoblastoma protein.
AB  - The retinoblastoma (RB) tumor suppressor protein is a transcriptional cofactor
      with essential roles in cell cycle and development. Physical and functional
      targets of RB and its paralogs p107/p130 have been studied largely in cultured
      cells, but the full biological context of this family of proteins' activities
      will likely be revealed only in whole organismal studies. To identify direct
      targets of the major Drosophila RB counterpart in a developmental context, we
      carried out ChIP-Seq analysis of Rbf1 in the embryo. The association of the
      protein with promoters is developmentally controlled; early promoter access is
      globally inhibited, whereas later in development Rbf1 is found to associate with
      promoter-proximal regions of approximately 2000 genes. In addition to conserved
      cell-cycle-related genes, a wholly unexpected finding was that Rbf1 targets many
      components of the insulin, Hippo, JAK/STAT, Notch, and other conserved signaling
      pathways. Rbf1 may thus directly affect output of these essential growth-control
      and differentiation pathways by regulation of expression of receptors, kinases
      and downstream effectors. Rbf1 was also found to target multiple levels of its
      own regulatory hierarchy. Bioinformatic analysis indicates that different classes
      of genes exhibit distinct constellations of motifs associated with the Rbf1-bound
      regions, suggesting that the context of Rbf1 recruitment may vary within the Rbf1
      regulon. Many of these targeted genes are bound by Rbf1 homologs in human cells,
      indicating that a conserved role of RB proteins may be to adjust the set point of
      interlinked signaling networks essential for growth and development.

PMID- 23173099
TI  - The cardio-protective signaling and mechanisms of adiponectin.
AB  - Adiponectin is an endogenous insulin-sensitizing hormone which has been found to
      regulate energy metabolism throughout the body, including the heart. However, low
      levels of adiponectin are found in patients with diabetes, hypertension and
      cardiovascular diseases. Thus it has been suggested to be an independent
      predictor for cardiovascular risk. Paradoxically, recent studies have also
      determined that adiponectin has cardioprotective effects against various cardiac
      related pathologies which lead to heart failure. These cardioprotective effects
      of adiponectin are attributed to its anti-inflammatory, anti-oxidant and anti
      apoptotic properties. Further findings suggest that locally produced adiponectin
      in cardiomyocytes are functional and biologically significant. This ectopic
      derived adiponectin exerts its protective effects through an autocrine mechanism.
      These data suggest adiponectin may serve as a potential therapeutic target
      against the development of pathologies which develop into heart failure. The
      current manuscript has summarized the key findings to date which explore the
      cardioprotective mechanisms of adiponectin against various cardiac pathologies.
      Further we explore the roles of both circulating and endogenous heart specific
      adiponectin and their physiological importance in various heart diseases.

PMID- 23173101
TI  - Valvular heart disease and 3-dimensional echocardiography: ready for prime-time?
AB  - Significant advances in 3-dimensional echocardiography (3DE) technology have
      ushered its use into clinical practice. The recent advent of real-time 3DE using
      matrix array transthoracic and transesophageal transducers has resulted in
      improved image spatial resolution, and therefore, enhanced visualization of the
      patho-morphological features of the cardiac valves. Three-dimensional
      echocardiography provides unique perspectives of valvular structures by
      presenting "en face" views of valvular structures, allowing for a better
      understanding of the topographical aspects of pathology, and a refined definition
      of the spatial relationships of intracardiac structures. Three-dimensional
      echocardiography makes available indices not described by 2D echocardiography and
      has been demonstrated to be superior to 2D echocardiography in a variety of
      valvular disease scenarios. In this review, we discuss the incremental role of
      3DE in evaluating valvular anatomic features, volumetric quantification, pre
      surgical planning, intra-procedural guidance, and post-procedural assessment of
      valvular heart disease.

PMID- 23173100
TI  - Genetic epidemiology of left ventricular hypertrophy.
AB  - Left ventricular (LV) hypertrophy is a strong independent predictor of increased
      cardiovascular morbidity and mortality in clinical and population-based samples.
      Clinical and hemodynamic stimuli to LV hypertrophy induce not only an increase in
      cardiac mass and wall thickness but also a fundamental reconfiguration of the
      protein, cellular and molecular components of the myocardium. Several studies
      have indicated that LV mass is influenced by genetic factors. The substantial
      heritability (h(2)) for LV mass in population-based samples of varying ethnicity
      indicates robust genetic influences on LV hypertrophy. Genome-wide linkage and
      association studies in diverse populations have been performed to identify genes
      influencing LV mass, and although several chromosomal regions have been found to
      be significantly associated with LV mass, the specific genes and functional
      variants contained in these chromosomal regions have yet to be identified. In
      addition, multiple studies have tried to link single-nucleotide polymorphisms
      (SNPs) in regulatory and pathway genes with common forms of LV hypertrophy, but
      there is little evidence that these genetic variations are functional. Up to this
      point in time, the results obtained in genetic studies are of limited clinical
      value. Much of the heritability remains unexplained, the identity of the
      underlying gene pathways, genes, and functional variants remains unknown, and the
      promise of genetically-based risk prediction and personalized medicine remain
      unfulfilled. However, molecular biological technologies continue to improve
      rapidly, and the long-term potential of sophisticated genetic investigations
      using these modern genomic technologies, coupled with smart study designs,
      remains intact. Ultimately, genetic investigations offer much promise for future
      prevention, early intervention and treatment of this major public health issue.

PMID- 23173102
TI  - Aortic vascular inflammation in psoriasis is associated with HDL particle size
      and concentration: a pilot study.
AB  - Psoriasis is a model Th1-mediated inflammatory disease associated with increased
      incidence of stroke and cardiovascular disease (CVD). The mechanism behind these
      associations is unknown, however abnormal HDL particle composition measured by
      nuclear magnetic resonance (NMR) spectroscopy has been shown to be associated
      with CVD. Using [18F]-fluorodeoxyglucose (FDG) positron emission tomography
      computed tomography (PET/CT), a validated surrogate marker of CVD, we assessed
      whether HDL particle size and concentration were associated with vascular
      inflammation in patients with psoriasis. Patients with psoriasis were
      prospectively enrolled (439 aortic samples from 10 patients). Lipoprotein
      profiles using NMR spectroscopy were obtained and the relationship between
      vascular inflammation within the thoracic aorta by FDG-PET/CT was analyzed for
      association with lipoprotein particle characteristics. The plasma total
      cholesterol (206 mg/dL (IQR 154-229)), LDL (105 (90-161)), and triglyceride
      levels were within normal range (151 (94-191)) while HDL levels were low (28.9
      (27.2-31.3)); however, the NMR profile demonstrated an atherogenic profile with
      increased small LDL and HDL particles. Total HDL particle concentration (p<0.001)
      and HDL particle size (p<0.001) were associated with decreased aortic
      inflammation, while concentration of small HDL particles was associated with
      increased inflammation (p<0.001). The association of total HDL particle
      concentration (beta -0.0113, p=0.002) and small HDL particle concentration (beta
      0.026, p<0.001) with aortic inflammation persisted following adjustment for CVD
      risk factors. Total HDL particle concentration and small HDL particle
      concentration were associated with vascular inflammation within the thoracic
      aorta in psoriasis. These findings suggest that HDL particle characteristics may
      play an important role in psoriatic vascular inflammation and CVD.

PMID- 23173103
TI  - A novel clinical indicator using cardiac technetium-99m sestamibi kinetics for
      evaluating cardiotoxicity in cancer patients treated with multiagent
      chemotherapy.
AB  - BACKGROUND: Multiagent chemotherapy (MCT) has mitochondrial targets. Since
      technetium-99m-sestamibi (MIBI) is a marker of mitochondrial metabolism, cardiac
      MIBI uptake and MIBI washout rate (%WR) may detect MCT-induced cardiotoxicity.
      METHODS: In 16 cancer patients on MCT for 10 months and in 14 non-cancer
      controls, cardiac MIBI uptake between early (30 min) and delayed (3 hours) post
      injection planar images was measured as counts per pixel (cpp). The MIBI cardiac
      %WR was also measured. RESULTS: When MCT patients and controls were compared,
      early and cardiac delayed MIBI uptake were greater in MCT patients (45 +/- 12 cpp
      vs. 30 +/- 4 cpp; p <0.04) and (30 +/- 8 cpp vs. 25 +/- 2 cpp; p < 0.02), but %
      WR did not change (12 +/- 4% vs. 13 +/- 3%; p = ns). However, in the MCT
      patients, the MIBI cardiac %WR was more rapid because it was obtained at the same
      time as in the control patients but from a greater amount of MIBI cardiac uptake.
      On 36-months follow-up, only MCT patients died of cardiac death. Overall survival
      risk parameters, only delayed cardiac MIBI uptake (Odds ratio = 1.7, p<0.001) and
      early cardiac MIBI uptake (Odds ratio = 1.2, p<0.02) were found to be
      significantly associated with cardiac mortality. CONCLUSIONS: In experimental
      studies, anticancer drugs elicit mitochondrial membrane hyperpolarization with
      passive cardiac MIBI uptake. In MCT patients, the increased cardiac MIBI uptake
      and rapid %WR compared with controls may reflect mitochondrial membrane
      dysfunction, pre-clinical cardiotoxicity and thus poor prognosis.

PMID- 23173104
TI  - Safety and efficacy of the Aperio thrombectomy device when compared to the
      Solitaire AB/FR and the Revive devices in a pulsatile flow system.
AB  - BACKGROUND AND PURPOSE: There are a limited number of studies comparing the
      Aperio mechanical thrombectomy device to other stent-based devices. In this
      paper, we compared the Aperio thrombectomy device to the Solitaire AB, FR and
      Revive devices in a model of the middle cerebral artery (MCA) within a modified
      pulsatile flow system. METHODS: Thrombi made of lamb's blood were placed into a
      pulsatile flow system perfused with Hartmann's solution at 80 bpm with a mean
      pressure of 90 mm Hg. 30 experiments were run with each device. RESULTS:
      Recanalization rates were similar for all three devices (90% with the Solitaire
      AB, FR, 80% with the Revive, and 90% with the Aperio). The mean number of
      attempts to retrieve the thrombus was also similar for all three devices (1.7
      with the Solitaire AB, FR, 2.1 with the Revive, 1.6 with the Aperio). Clot
      fragmentation and embolization rates revealed no statistical significance but
      there was a trend towards lower embolization rates with the Aperio (23% compared
      to 40% with the Solitaire AB, FR and 47% with the Revive). The Aperio was the
      fastest to recanalize the MCA (mean of 66 seconds compared to 186 seconds for the
      Solitaire AB, FR and 169 seconds for the Revive). CONCLUSIONS: In this in vitro
      setting, the Aperio device seems to be an efficacious and safe device when
      compared to other similar clinically used mechanical thrombectomy devices. Larger
      clinical trials are warranted.

PMID- 23173105
TI  - Subclinical, hemodynamic, and echocardiographic abnormalities of high pulse
      pressure in hypertensive and non-hypertensive adults.
AB  - BACKGROUND: High pulse pressure (PP) is associated with cardiovascular events,
      but subclinical abnormalities in cardiac structure and function in relation to
      high pulse pressure are not well described. METHODS AND RESULTS: 2225
      hypertensive and 1380 non-hypertensive participants with adequate
      echocardiographic left ventricular measurements were evaluated. Non-hypertensives
      in the highest PP tertile (compared to the lower tertiles) were older (44 years
      vs. 40 years, p<0.009), had higher systolic pressure [(SBP) 136 mmHg vs. 108
      mmHg] and lower diastolic pressure [(DBP) 54 vs. 71 mmHg (p=.0001)], greater BMI
      (27 vs. 25 kg/m2, p<.001) and more diabetes (4% vs. 2.25%, p<.001). In the
      hypertensive group, subjects in the highest PP tertile were older (52 vs 42
      years), had higher SBP (157 vs. 116 mmHg) but lower DBP (65 vs. 83 mmHg). In the
      non-hypertensive group, higher PP (>60 mmHG) was associated with a higher
      frequency of echocardiographic structural and functional abnormalities,
      specifically, greater posterior and relative wall thickness, longer isovolumic
      relaxation time, and concentric left ventricular (LV) hypertrophy. CONCLUSION: In
      a population-based sample of hypertensive and non-hypertensive participants,
      higher PP was associated with subclinical abnormalities of cardiac structure and
      function, which exist even in the absence of hypertension and/or the use of
      antihypertensive treatment.

PMID- 23173106
TI  - Abdominal aortic aneurysm and the association with serum levels of Homocysteine,
      vitamins B6, B12 and Folate.
AB  - Previous investigations have shown hyperhomocysteinemi in patients with abdominal
      aortic aneurysm (AAA). In the present study we evaluated the circulating level of
      homocysteine (Hcy) in relation to renal function, vitamins B6, B12 and folate
      status in AAA patients with special regard to aneurysm size, and rupture. Hcy,
      Creatinine, B6, B12 and folate were measured in 119 patients with AAA and 36
      controls without aneurysm matched by age, gender and smoking habit. As expected
      there was a weak correlation between Hcy and vitamins B6, B12 or folate. We found
      similar levels of Hcy, B6 and folic acid in patients with nonruptured AAA
      compared to the control group matched by age, gender and smoking habit. There was
      no correlation between maximum diameter of the nonruptured AAA (n=78) and Hcy, B6
      or folate. However, the present study shows a significant inverse correlation
      between maximum diameter of the nonruptured AAA (n=78) and B12 (r = -0.304,
      p=0.007) with significant higher levels in small AAA compared to large AAA. In
      conclusion, Hcy does not seem to be a useful biomarker in AAA disease. The
      unexpected finding of B12 levels correlating to aneurysm diameter warrants urgent
      further investigation of B12 supplement to prevent progression of small AAA.

PMID- 23173107
TI  - Neck circumference and central obesity are independent predictors of coronary
      artery disease in patients undergoing coronary angiography.
AB  - Excess of adiposity is a risk factor for coronary artery disease, but it remains
      unclear if the distribution of fat is an effect modifier or if the risk is
      mediate by hypertension, diabetes and dyslipidemia. We investigated the
      association of central in addition to general obesity with coronary artery
      disease (CAD). A case-control study was conducted in 376 patients, aged 40 years
      or more, with chronic coronary disease, undergoing elective coronary angiography.
      Excess of adiposity was evaluated by the Body Mass Index (BMI), waist
      circumference, waist-hip ratio, and neck circumference. Cases (n=155) were
      patients referred for coronary angiography with at least 50% of coronary stenosis
      in at least one epicardial vessels or their branches, with diameter greater than
      2.5 mm. Controls (n=221) were patients referred for coronary angiography without
      significant coronary disease. Odds ratios and 95%CI for significant coronary
      stenosis were calculated using multiple logistic regression, controlling for age,
      sex, years at school, smoking, hypertension, HDL-cholesterol, diabetes mellitus,
      and an adiposity index. There was a predominance of men and individuals older
      than 50 years among cases. The waist-hip ratio increased four times the chance of
      CAD, even after the control for confounding factors, including BMI. Neck
      circumference above the 90(th) Percentile doubled the chance of CAD, after
      adjustment for traditional risk factors. Neck circumference and waist-hip ratio
      are independent predictors of CAD, even taking into account traditional risk
      factors for CAD. These findings highlight the need of anthropometric assessment
      among patients with suspected coronary artery disease.

PMID- 23173108
TI  - Renal infarction secondary to cor triatriatum sinister.
AB  - A 30 year old, otherwise healthy man presented with flank pain and was ultimately
      found to have a rightsided renal infarction. Transthoracic echocardiography
      suggested, and then transesophageal echocardiography (TEE) confirmed, the
      presence of cor triatriatum sinister. Given the lack of other sources of emboli,
      this was felt to be the most likely source. We describe the case and both the
      echocardiographic and CT findings of this rare condition. This case demonstrates
      the need for TEE in some cases where 2D echocardiography is not sensitive enough
      to "rule out" cardio-embolic sources. This is only the second case in the
      literature of a systemic embolization due to cor triatriatum, and the first one
      in the Western literature.

PMID- 23173109
TI  - Strategy for prevention of hip fractures in patients with Parkinson's disease.
AB  - Hypovitaminosis D and K due to malnutrition or sunlight deprivation, increased
      bone resorption due to immobilization, low bone mineral density (BMD) and an
      increased risk of falls may contribute to an increased risk of hip fractures in
      patients with Parkinson's disease. The purpose of the present study was to
      clarify the efficacy of interventions intended to prevent hip fractures in
      elderly patients with Parkinson's disease. PubMed was used to search the
      literature for randomized controlled trials (RCTs) regarding Parkinson's disease
      and hip fractures. The inclusion criteria were 50 or more subjects per group and
      a study period of 1 year or longer. Five RCTs were identified and the relative
      risk and 95% confidence interval were calculated for individual RCTs. Sunlight
      exposure increased serum hydroxyvitamin D [25(OH)D] concentration, improved motor
      function, decreased bone resorption and increased BMD. Alendronate or risedronate
      with vitamin D supplementation increased serum 25(OH)D concentration, strongly
      decreased bone resorption and increased BMD. Menatetrenone (vitamin K(2))
      decreased serum undercarboxylated osteocalcin concentration, decreased bone
      resorption and increased BMD. Sunlight exposure (men and women), menatetrenone
      (women), alendronate and risedronate with vitamin D supplementation (women)
      significantly reduced the incidence of hip fractures. The respective RRs (95%
      confidence intervals) according to the intention-to-treat analysis were 0.27
      (0.08, 0.96), 0.13 (0.02, 0.97), 0.29 (0.10, 0.85) and 0.20 (0.06, 0.68).
      Interventions, including sunlight exposure, menatetrenone and oral
      bisphosphonates with vitamin D supplementation, have a protective effect against
      hip fractures elderly patients with Parkinson's disease.

PMID- 23173110
TI  - RANKL-RANK interaction in immune regulatory systems.
AB  - The interaction between the receptor activator of NF-kappaB ligand (RANKL) and
      its receptor RANK plays a critical role in the development and function of
      diverse tissues. This review summarizes the studies regarding the functions of
      RANKL signaling in immune regulatory systems. Previous in vitro and in vivo
      studies have indicated that the RANKL signal promotes the survival of dendritic
      cells (DCs), thereby activating the immune response. In addition, RANKL signaling
      to DCs in the body surface barriers controls self-tolerance and oral-tolerance
      through regulatory T cell functions. In addition to regulating DC functions, the
      RANKL and RANK interaction is critical for the development and organization of
      several lymphoid organs. The RANKL signal initiates the formation of clusters of
      lymphoid tissue inducer cells, which is crucial for lymph node organogenesis.
      Moreover, the RANKL-RANK interaction controls the differentiation of M cells,
      specialized epithelial cells in mucosal tissues, that take up and transcytose
      antigen particles to control the immune response to pathogens or commensal
      bacterium. The development of epithelial cells localized in the thymic medulla
      (mTECs) is also regulated by the RANKL-RANK signal. Given that the unique
      property of mTECs to express a wide variety of tissue-specific self-antigens is
      critical for the elimination of self-antigen reactive T cells in the thymus, the
      RANKL-RANK interaction contributes to the suppression of autoimmunity. Future
      studies on the roles of the RANKL-RANK system in immune regulatory functions
      would be informative for the development and application of inhibitors of RANKL
      signaling for disease treatment.

PMID- 23173112
TI  - Statistical virtual eye model based on wavefront aberration.
AB  - Wavefront aberration affects the quality of retinal image directly. This paper
      reviews the representation and reconstruction of wavefront aberration, as well as
      the construction of virtual eye model based on Zernike polynomial coefficients.
      In addition, the promising prospect of virtual eye model is emphasized.

PMID- 23173111
TI  - Injury patterns of seniors in traffic accidents: A technical and medical
      analysis.
AB  - AIM: To investigate the actual injury situation of seniors in traffic accidents
      and to evaluate the different injury patterns. METHODS: Injury data,
      environmental circumstances and crash circumstances of accidents were collected
      shortly after the accident event at the scene. With these data, a technical and
      medical analysis was performed, including Injury Severity Score, Abbreviated
      Injury Scale and Maximum Abbreviated Injury Scale. The method of data collection
      is named the German In-Depth Accident Study and can be seen as representative.
      RESULTS: A total of 4430 injured seniors in traffic accidents were evaluated. The
      incidence of sustaining severe injuries to extremities, head and maxillofacial
      region was significantly higher in the group of elderly people compared to a
      younger age (P < 0.05). The number of accident-related injuries was higher in the
      group of seniors compared to other groups. CONCLUSION: Seniors are more likely to
      be involved in traffic injuries and to sustain serious to severe injuries
      compared to other groups.

PMID- 23173113
TI  - Conductive keratoplasty: an approach for the correction of residual hyperopia in
      post-lasik pseudophakia.
AB  - Although there are many formulae for the calculation of intraocular lens power in
      the eyes with previous kerato-refractive surgeries, unexpected refractive bias
      still exists. Hyperopic bias is particularly disliked because it affects both
      uncorrected distance and near visual acuity. Surgical treatment of the residual
      hyperopia for the eyes with both laser in situ keratomileusis and cataract
      surgery remains to be a big problem. Conductive keratoplasty has been shown to be
      an effective, safe and predictable method for low and moderate hyperopia in the
      pseudophakic eyes or in the eyes with kerato-refractive surgeries. However, the
      efficacy and safety of conductive keratoplasty in the correction of residual
      hyperopia after both corneal and lens refractive surgeries has not been reported.
      Herein, we reported the surgical correction with conductive keratoplasty for
      cases of residual hyperopia with/without astigmatism after previous laser in situ
      keratomileusis for high myopia and following phacoemulsification combined with
      posterior intraocular lens implantation for complicated cataract.

PMID- 23173114
TI  - Reader's Forum.

PMID- 23173115
TI  - Three-dimensional analysis of dental decompensation for skeletal Class III
      malocclusion on the basis of vertical skeletal patterns obtained using cone-beam
      computed tomography.
AB  - OBJECTIVE: To evaluate the presurgical orthodontic tooth movement of mandibular
      teeth after dental decompensation for skeletal Class III deformities on the basis
      of vertical skeletal patterns. METHODS: This cohort was comprised of 62 patients
      who received presurgical orthodontic treatment. These patients were divided into
      3 groups according to their vertical skeletal patterns. Changes in the positions
      of the mandibular central incisor, canine, premolar, and 1st molar after
      presurgical orthodontic treatment were measured using a cone-beam computed
      tomography (CBCT) superimposition method. RESULTS: The incisors moved forward
      after dental decompensation in all 3 groups. The canines in group I and the 1st
      premolars in groups I and III also moved forward. The incisors and canines were
      extruded in groups I and II. The 1st and 2nd premolars were also extruded in all
      groups. Vertical changes in the 1st premolars differed significantly between the
      groups. We also observed lateral movement of the canines in group III and of the
      1st premolar, 2nd premolar, and 1st molar in all 3 groups (p < 0.05).
      CONCLUSIONS: Movement of the mandibular incisors and premolars resolved the
      dental compensation. The skeletal facial pattern did not affect the dental
      decompensation, except in the case of vertical changes of the 1st premolars.

PMID- 23173116
TI  - Validity of palatal superimposition of 3-dimensional digital models in cases
      treated with rapid maxillary expansion and maxillary protraction headgear.
AB  - OBJECTIVE: The purpose of this study was to evaluate the validity of the 3
      dimensional (3D) superimposition method of digital models in patients who
      received treatment with rapid maxillary expansion (RME) and maxillary protraction
      headgear. METHODS: The material consisted of pre- and post-treatment maxillary
      dental casts and lateral cephalograms of 30 patients, who underwent RME and
      maxillary protraction headgear treatment. Digital models were superimposed using
      the palate as a reference area. The movement of the maxillary central incisor and
      the first molar was measured on superimposed cephalograms and 3D digital models.
      To determine whether any difference existed between the 2 measuring techniques,
      intra-class correlation (ICC) and Bland-Altman plots were analyzed. RESULTS: The
      measurements on the 3D digital models and cephalograms showed a very high
      correlation in the antero-posterior direction (ICC, 0.956 for central incisor and
      0.941 for first molar) and a moderate correlation in the vertical direction (ICC,
      0.748 for central incisor and 0.717 for first molar). CONCLUSIONS: The 3D model
      superimposition method using the palate as a reference area is as clinically
      reliable for assessing antero-posterior tooth movement as cephalometric
      superimposition, even in cases treated with orthopedic appliances, such as RME
      and maxillary protraction headgear.

PMID- 23173117
TI  - Comparison of success rates of orthodontic mini-screws by the insertion method.
AB  - OBJECTIVE: The aim of this study was to compare the success rates of the manual
      and motor-driven mini-screw insertion methods according to age, gender, length of
      mini-screws, and insertion sites. METHODS: We retrospectively reviewed 429
      orthodontic mini-screw placements in 286 patients (102 in men and 327 in women)
      between 2005 and 2010 at private practice. Age, gender, mini-screw length, and
      insertion site were cross-tabulated against the insertion methods. The Cochran
      Mantel-Haenszel test was performed to compare the success rates of the 2
      insertion methods. RESULTS: The motor-driven method was used for 228 mini-screws
      and the manual method for the remaining 201 mini-screws. The success rates were
      similar in both men and women irrespective of the insertion method used. With
      respect to mini-screw length, no difference in success rates was found between
      motor and hand drivers for the 6-mm-long mini-screws (68.1% and 69.5% with the
      engine driver and hand driver, respectively). However, the 8-mm-long mini-screws
      exhibited significantly higher success rates (90.4%, p < 0.01) than did the 6-mm
      long mini-screws when placed with the engine driver. The overall success rate was
      also significantly higher in the maxilla (p < 0.05) when the engine driver was
      used. Success rates were similar among all age groups regardless of the insertion
      method used. CONCLUSIONS: Taken together, the motor-driven insertion method can
      be helpful to get a higher success rate of orthodontic mini-screw placement.

PMID- 23173118
TI  - Skeletal myogenic differentiation of human periodontal ligament stromal cells
      isolated from orthodontically extracted premolars.
AB  - OBJECTIVE: To investigate the stem cell-like characteristics of human periodontal
      ligament (PDL) stromal cells outgrown from orthodontically extracted premolars
      and to evaluate the potential for myogenic differentiation. METHODS: PDL stromal
      cells were obtained from extracted premolars by using the outgrowth method. Cell
      morphological features, self-replication capability, and the presence of cell
      surface markers, along with osteogenic, adipogenic, and chondrogenic
      differentiation, were confirmed. In addition, myogenic differentiation was
      induced by the use of 5-aza-2'-deoxycytidine (5-Aza) for DNA demethylation.
      RESULTS: PDL stromal cells showed growth patterns and morphological features
      similar to those of fibroblasts. In contrast, the proliferation rates of premolar
      PDL stromal cells were similar to those of bone marrow and adipogenic stem cells.
      PDL stromal cells expressed surface markers of human mesenchymal stem cells
      (i.e., CD90 and CD105), but not those of hematopoietic stem cells (i.e., CD31 and
      CD34). PDL stromal cells were differentiated into osteogenic, adipogenic, and
      chondrogenic lineages. Myotube structures were induced in PDL stromal cells after
      5-Aza pretreatment, but not in the absence of 5-Aza pretreatment. CONCLUSIONS:
      PDL stromal cells isolated from extracted premolars can potentially be a good
      source of postnatal stem cells for oromaxillofacial regeneration in bone and
      muscle.

PMID- 23173119
TI  - Comparison of retention characteristics of Essix and Hawley retainers.
AB  - OBJECTIVE: We aimed to compare the retention characteristics of Essix and Hawley
      retainers. METHODS: Adolescents undergoing fixed appliance treatment at 2 centers
      were recruited for this study. Twenty-two patients (16 women and 6 men) wore
      Essix retainers (Essix group) while 20 (14 women and 6 men) wore Hawley retainers
      (Hawley group). The mean retention time was 1 year, and the mean follow-up recall
      time for both groups was 2 years. Two qualified dental examiners evaluated the
      blind patient data. Maxillary and mandibular dental casts and lateral
      cephalograms were analyzed at 4 stages: pretreatment (T1), post-treatment (T2),
      post-retention (T3), and follow-up (T4). RESULTS: The results revealed that Essix
      appliances were more efficient in retaining the anterior teeth in the mandible
      during a 1-year retention period. The irregularity index increased in both arches
      in both groups after a 2-year post-retention period. The mandibular arch lengths
      increased during treatment and tended to return to their original value after
      retention in both groups; however, these changes were statistically significant
      only in the Hawley group. Cephalometric variables did not show any significant
      differences. CONCLUSIONS: The retention characteristics of both Essix and Hawley
      retainers are similar.

PMID- 23173120
TI  - Antimicrobial effect of different brushing frequencies with fluoride toothpaste
      on Streptococcus mutans and Lactobacillus species in children with fixed
      orthodontic appliances.
AB  - OBJECTIVE: To evaluate the antimicrobial effect of different frequencies of
      brushing with fluoride toothpaste on the levels of salivary mutans streptococci
      and lactobacilli in children undergoing fixed orthodontic treatment. METHODS: The
      study included 22 patients scheduled for fixed orthodontic therapy distributed
      between 2 groups with different hygiene regimes. All the subjects received
      identical braces, bands, and brackets bonded with the same material. Stimulated
      saliva samples were obtained before placement of the appliance and at 6, 12, and
      18 weeks during the therapy. Saliva samples were cultured on selective microbial
      agar for the detection of microorganisms. RESULTS: Salivary mutans streptococci
      were significantly suppressed throughout the experimental period in the group
      that brushed 4 times a day as compared to the group that brushed twice a day.
      Salivary lactobacilli were not significantly affected by the frequency of
      brushing with 0.32% sodium fluoride (NaF) toothpaste. CONCLUSIONS: The use of
      0.32% NaF-containing toothpaste more than 3 times a day has effective
      antimicrobial activity on mutans streptococci but not lactobacilli in the saliva
      of children with fixed orthodontic appliances.

PMID- 23173121
TI  - Correction of dental Class III with posterior open bite by simple biomechanics
      using an anterior C-tube miniplate.
AB  - In the correction of dental Class III molar relationship in skeletal Class II
      patients, uprighting of the mandibular posterior segments without opening the
      mandible is an important treatment objective. In the case reported herein, a C
      tube miniplate fixed to the lower labial symphysis and connected with a nickel
      titanium reverse-curved archwire provided effective uprighting of the lower
      molars, without the need of orthodontic appliances on the mandibular anteriors.
      Using this approach, an appropriate magnitude of force is exerted on the molars
      while avoiding any negative effect on the mandibular anteriors.

PMID- 23173122
TI  - Chemical composition of human and canine fascia lata.
AB  - The fascial system is an integral part of the musculoskeletal system. It is a
      three-dimensional network of connective tissue spreading ubiquitously throughout
      the body, surrounding muscles, bones, internal organs, nerves, vessels, and other
      structures. The basic biophysical properties of the fascial system are determined
      by its structure and chemical composition. This study aimed to determine the
      elemental composition of pathologically unchanged fascia lata of the thigh,
      collected during autopsies on humans and dogs. The wide spectrum of elements
      analysed included both macro and micro elements. The analyses were conducted
      using scanning electron microscopy with X-ray microanalysis (SEM-EDS).
      Concentrations of the following macro and micro elements were determined: C, N,
      O, Na, Mg, Al, Si, P, S, Cl, K, Ca, Ti, Fe Co, Ni, Cu, and Zn. The obtained
      results showed significant differences between human and canine fascia lata
      regarding the content of most of the examined elements (p < 0.05), except for N.
      These data may in future provide a starting point for the establishment of
      reference values for the content of various elements in normal fascial tissue and
      may also serve to verify the usefulness of experimental animal material as a
      substitute for human tissue.

PMID- 23173123
TI  - Vps41, a protein involved in lysosomal trafficking, interacts with caspase-8.
AB  - Caspase-8 is a member of the cysteine-aspartic acid protease (caspase) family
      which plays a central role in apoptosis and development. We screened caspase-8
      interacting proteins from mouse T-cell lymphoma and 7.5-day embryo cDNA libraries
      by yeast two-hybrid system and obtained eleven positive clones, including
      Vacuolar protein sorting 41 (Vps41), a protein involved in trafficking of
      proteins from the late Golgi to the vacuole. The interaction of Vps41 with
      caspase-8 was confirmed by co-immunoprecipitation (co-IP) and co-localization
      studies in HEK293T cells. Co-IP experiments also showed that Vps41 binds to the
      p18 subunit of caspase-8 through its WD40 region and RING-finger motif.
      Furthermore, we found that overexpression of Vps41 promotes Fas-induced apoptosis
      in A549 human lung adenocarcinoma cells. The cleavage of caspase-3, a caspase-8
      downstream effector, was increased when cells were transfected with Vps41
      overexpressing plasmid. Together, these results suggest a novel interaction of
      caspase-8 with Vps41 and provide a potential role of Vps41 beyond lysosomal
      trafficking.

PMID- 23173124
TI  - The role of microRNA in metastatic colorectal cancer and its significance in
      cancer prognosis and treatment.
AB  - microRNAs (miRNAs) are small, non-coding RNA molecules that regulate gene
      expression by targeting specific mRNAs. microRNAs play a role in several
      physiological processes in the cell, including migration, proliferation,
      differentiation and apoptosis. Apart from their role in regular metabolism,
      abnormal profiles of miRNA expression accompany cancer transformation, including
      colorectal cancer (CRC) metastasis. microRNAs may play a role in each phase of
      CRC metastasis including angiogenesis, invasion, intravasation, circulation,
      extravasation and metastatic colonization. microRNA levels may serve as a
      predictive CRC marker, which was confirmed by the serum level of miR-29a
      targeting KLF4, a marker of cell stemness, and the plasma level of miR-221 down
      regulating c-Kit, Stat5A and ETS1, which are signal transducers and transcription
      factor, respectively. In turn, the level of miR-143 in CRC cells decreasing the
      amount of MACC1 (metastasis-associated in colon cancer-1) and oncogenic KRAS
      protein, may be utilized as a prognostic marker. Also, single nucleotide
      polymorphisms of genes encoding miRNAs, including miR-423 and miR-608, which
      correlate with tumor recurrence, may be useful as diagnostic, prognostic and
      predictive indicators in CRC metastasis. Pre-miR-34a and pre-miR-199a decreased
      the level of Axl, a tyrosine-protein kinase receptor, so they can be considered
      as drugs in antimetastatic therapy. On the other hand, miR-222 targeting ADAM-17,
      a disintegrin and metalloproteinase, and miR-328 interacting with ABCG2, an ABC
      transporter, may overcome drug resistance of cancer cells. microRNAs may be
      considered in wide-range application to facilitate CRC metastasis diagnosis,
      prognosis, prediction and therapy, however, further clinical, epidemiological and
      in vitro studies should be conducted to verify their utility.

PMID- 23173125
TI  - "New twist" in Diabetes Care for HbA(1c) reporting: "it takes two to tango"!

PMID- 23173126
TI  - The imperative to prevent diabetes.

PMID- 23173127
TI  - Incidence of major amputation for diabetes in Scotland sets a target for us all.

PMID- 23173128
TI  - When the blood glucose and the HbA(1c) don't match: turning uncertainty into
      opportunity.

PMID- 23173129
TI  - S.O.S.

PMID- 23173130
TI  - Glargine and cancer: can we now suggest closure?

PMID- 23173131
TI  - The start of something good: the discovery of HbA(1c) and the American Diabetes
      Association Samuel Rahbar Outstanding Discovery Award.

PMID- 23173132
TI  - Diabetes: have we got it all wrong? Insulin hypersecretion and food additives:
      cause of obesity and diabetes?

PMID- 23173133
TI  - Diabetes: have we got it all wrong? Hyperinsulinism as the culprit: surgery
      provides the evidence.

PMID- 23173134
TI  - Projections of type 1 and type 2 diabetes burden in the U.S. population aged <20
      years through 2050: dynamic modeling of incidence, mortality, and population
      growth.
AB  - OBJECTIVE: To forecast the number of U.S. individuals aged <20 years with type 1
      diabetes mellitus (T1DM) or type 2 diabetes mellitus (T2DM) through 2050,
      accounting for changing demography and diabetes incidence. RESEARCH DESIGN AND
      METHODS: We used Markov modeling framework to generate yearly forecasts of the
      number of individuals in each of three states (diabetes, no diabetes, and death).
      We used 2001 prevalence and 2002 incidence of T1DM and T2DM from the SEARCH for
      Diabetes in Youth study and U.S. Census Bureau population demographic
      projections. Two scenarios were considered for T1DM and T2DM incidence: 1)
      constant incidence over time; 2) for T1DM yearly percentage increases of 3.5,
      2.2, 1.8, and 2.1% by age-groups 0-4 years, 5-9 years, 10-14 years, and 15-19
      years, respectively, and for T2DM a yearly 2.3% increase across all ages.
      RESULTS: Under scenario 1, the projected number of youth with T1DM rises from
      166,018 to 203,382 and with T2DM from 20,203 to 30,111, respectively, in 2010 and
      2050. Under scenario 2, the number of youth with T1DM nearly triples from 179,388
      in 2010 to 587,488 in 2050 (prevalence 2.13/1,000 and 5.20/1,000 [+144%
      increase]), with the greatest increase in youth of minority racial/ethnic groups.
      The number of youth with T2DM almost quadruples from 22,820 in 2010 to 84,131 in
      2050; prevalence increases from 0.27/1,000 to 0.75/1,000 (+178% increase).
      CONCLUSIONS: A linear increase in diabetes incidence could result in a
      substantial increase in the number of youth with T1DM and T2DM over the next 40
      years, especially those of minority race/ethnicity.

PMID- 23173135
TI  - Metformin and the risk of cancer: time-related biases in observational studies.
AB  - OBJECTIVE: Time-related biases in observational studies of drug effects have been
      described extensively in different therapeutic areas but less so in diabetes.
      Immortal time bias, time-window bias, and time-lag bias all tend to greatly
      exaggerate the benefits observed with a drug. RESEARCH DESIGN AND METHODS: These
      time-related biases are described and shown to be prominent in observational
      studies that have associated metformin with impressive reductions in the
      incidence of and mortality from cancer. As a consequence, metformin received much
      attention as a potential anticancer agent; these observational studies sparked
      the conduction of randomized, controlled trials of metformin as cancer treatment.
      However, the spectacular effects reported in these studies are compatible with
      time-related biases. RESULTS: We found that 13 observational studies suffered
      from immortal time bias; 9 studies had not considered time-window bias, whereas
      other studies did not consider inherent time-lagging issues when comparing the
      first-line treatment metformin with second- or third-line treatments. These
      studies, subject to time-related biases that are avoidable with proper study
      design and data analysis, led to illusory extraordinarily significant effects,
      with reductions in cancer risk with metformin ranging from 20 to 94%. Three
      studies that avoided these biases reported no effect of metformin use on cancer
      incidence. CONCLUSIONS: Although observational studies are important to better
      understand the effects of drugs, their proper design and analysis is essential to
      avoid major time-related biases. With respect to metformin, the scientific
      evidence of its potential beneficial effects on cancer would need to be
      reassessed critically before embarking on further long and expensive trials.

PMID- 23173136
TI  - Measurement of hemoglobin A(1c): a new twist on the path to harmony.

PMID- 23173138
TI  - Immune response of hepatitis B vaccine among persons with diabetes: a systematic
      review of the literature.

PMID- 23173137
TI  - Changing physical activity behavior in type 2 diabetes: a systematic review and
      meta-analysis of behavioral interventions.
AB  - OBJECTIVE: Behavioral interventions targeting "free-living" physical activity
      (PA) and exercise that produce long-term glycemic control in adults with type 2
      diabetes are warranted. However, little is known about how clinical teams should
      support adults with type 2 diabetes to achieve and sustain a physically active
      lifestyle. RESEARCH DESIGN AND METHODS: We conducted a systematic review of
      randomized controlled trials (RCTs) (published up to January 2012) to establish
      the effect of behavioral interventions (compared with usual care) on free-living
      PA/exercise, HbA(1c), and BMI in adults with type 2 diabetes. Study
      characteristics, methodological quality, practical strategies for increasing
      PA/exercise (taxonomy of behavior change techniques), and treatment fidelity
      strategies were captured using a data extraction form. RESULTS: Seventeen RCTs
      fulfilled the review criteria. Behavioural interventions showed statistically
      significant increases in objective (standardized mean difference [SMD] 0.45, 95%
      CI 0.21-0.68) and self-reported PA/exercise (SMD 0.79, 95% CI 0.59-0.98)
      including clinically significant improvements in HbA(1c) (weighted mean
      difference [WMD] -0.32%, 95% CI -0.44% to -0.21%) and BMI (WMD -1.05 kg/m(2), 95%
      CI -1.31 to -0.80). Few studies provided details of treatment fidelity strategies
      to monitor/improve provider training. Intervention features (e.g., specific
      behavior change techniques, interventions underpinned by behavior change
      theories/models, and use of >=10 behaviour change techniques) moderated
      effectiveness of behavioral interventions. CONCLUSIONS: Behavioral interventions
      increased free-living PA/exercise and produced clinically significant
      improvements in long-term glucose control. Future studies should consider use of
      theory and multiple behavior change techniques associated with clinically
      significant improvements in HbA(1c), including structured training for care
      providers on the delivery of behavioural interventions.

PMID- 23173139
TI  - Basal supplementation of insulin lispro protamine suspension versus insulin
      glargine and detemir for type 2 diabetes: meta-analysis of randomized controlled
      trials.
AB  - OBJECTIVE: We compared the effect of insulin lispro protamine suspension (ILPS)
      with that of insulin glargine and insulin detemir, all given as basal
      supplementation, in the treatment of patients with type 2 diabetes. RESEARCH
      DESIGN AND METHODS: We conducted an electronic search until February 2012,
      including online registries of ongoing trials and abstract books. All randomized
      controlled trials comparing ILPS with insulin glargine or detemir with a duration
      of >=12 weeks were included. RESULTS: We found four trials lasting 24-36 weeks
      involving 1,336 persons: three studies compared ILPS with glargine, and one trial
      compared ILPS with detemir. There was no significant difference in change in
      HbA(1c) level between ILPS and comparators, in the proportion of patients
      achieving the HbA(1c) goals of <=6.5 or <7%, in weight change, or in daily
      insulin doses. There was no difference in overall hypoglycemia, but nocturnal
      hypoglycemia occurred significantly more with ILPS than with comparator insulins
      (mean difference 0.099 events/patient/30 days [95% CI 0.03-0.17]). In a
      prespecified sensitivity analysis comparing data obtained in patients who
      remained on their once-daily insulin regimen, not significantly different event
      rates for nocturnal hypoglycemia were observed between ILPS and comparator
      insulins (0.063 [-0.007 to 0.13]), and ILPS was associated with lower insulin
      dose (0.07 units/kg/day [0.05-0.09]). CONCLUSIONS: There is no difference between
      ILPS and insulin glargine or detemir for targeting hyperglycemia, but nocturnal
      hypoglycemia occurred more frequently with ILPS than with comparator insulins.
      Nocturnal hypoglycemia was not significantly different in people who injected
      insulin once daily.

PMID- 23173140
TI  - Pharmacist interventions to improve cardiovascular disease risk factors in
      diabetes: a systematic review and meta-analysis of randomized controlled trials.
AB  - OBJECTIVE: This systematic review and meta-analysis of randomized controlled
      trials (RCTs) assesses the effect of pharmacist care on cardiovascular disease
      (CVD) risk factors among outpatients with diabetes. RESEARCH DESIGN AND METHODS:
      MEDLINE, EMBASE, CINAHL, and the Cochrane Central Register of Controlled Trials
      were searched. Pharmacist interventions were classified, and a meta-analysis of
      mean changes of blood pressure (BP), total cholesterol (TC), LDL cholesterol, HDL
      cholesterol, and BMI was performed using random-effects models. RESULTS: The meta
      analysis included 15 RCTs (9,111 outpatients) in which interventions were
      conducted exclusively by pharmacists in 8 studies and in collaboration with
      physicians, nurses, dietitians, or physical therapists in 7 studies. Pharmacist
      interventions included medication management, educational interventions, feedback
      to physicians, measurement of CVD risk factors, or patient-reminder systems.
      Compared with usual care, pharmacist care was associated with significant
      reductions for systolic BP (12 studies with 1,894 patients; -6.2 mmHg [95% CI 
      7.8 to -4.6]); diastolic BP (9 studies with 1,496 patients; -4.5 mmHg [-6.2 to 
      2.8]); TC (8 studies with 1,280 patients; -15.2 mg/dL [-24.7 to -5.7]); LDL
      cholesterol (9 studies with 8,084 patients; -11.7 mg/dL [-15.8 to -7.6]); and BMI
      (5 studies with 751 patients; -0.9 kg/m(2) [-1.7 to -0.1]). Pharmacist care was
      not associated with a significant change in HDL cholesterol (6 studies with 826
      patients; 0.2 mg/dL [-1.9 to 2.4]). CONCLUSIONS: This meta-analysis supports
      pharmacist interventions-alone or in collaboration with other health care
      professionals-to improve major CVD risk factors among outpatients with diabetes.

PMID- 23173142
TI  - Bariatric surgery does not exacerbate and may be beneficial for the microvascular
      complications of type 2 diabetes.

PMID- 23173143
TI  - The TOSCA.IT trial: a study designed to evaluate the effect of pioglitazone
      versus sulfonylureas on cardiovascular disease in type 2 diabetes.

PMID- 23173144
TI  - Sitagliptin successfully ameliorates glycemic control in Werner syndrome with
      diabetes.

PMID- 23173145
TI  - Vitamin B(12) deficiency associated with concomitant metformin and proton pump
      inhibitor use.

PMID- 23173146
TI  - Point-of-care measurements of HbA(1c): simplicity does not mean laxity with
      controls.

PMID- 23173147
TI  - Comment on: Holstein et al. Substantial increase in incidence of severe
      hypoglycemia between 1997-2000 and 2007-2010: a german longitudinal population
      based study. Diabetes Care 2012;35:972-975.

PMID- 23173149
TI  - Comment on: Gruden et al. Severe hypoglycemia and cardiovascular disease
      incidence in type 1 diabetes: the EURODIAB prospective complications study.
      Diabetes Care 2012;35:1598-1604.

PMID- 23173151
TI  - Comment on: Stefanovski et al. Estimating hepatic glucokinase activity using a
      simple model of lactate kinetics. Diabetes Care 2012;35:1015-1020.

PMID- 23173153
TI  - Comment on: Park et al. Association of serum ferritin and the development of
      metabolic syndrome in middle-aged Korean men: a 5-year follow-up study. Diabetes
      Care 2012;35:2521-2526.

PMID- 23173154
TI  - Lower blood pressure associated with higher mortality in retrospective study of
      patients with newly diagnosed type 2 diabetes.

PMID- 23173155
TI  - N-3 fatty acids did not reduce major cardiovascular events in patients with
      dysglycaemia.

PMID- 23173169
TI  - Birth weight of Korean infants is affected by the interaction of maternal iron
      intake and GSTM1 polymorphism.
AB  - Excessive iron consumption during pregnancy can lead to increased oxidative
      stress in the maternal body, which may result in adverse pregnancy outcomes.
      Glutathione S-transferases (GSTs) originate from a superfamily of detoxifying
      enzymes that play a role in reducing xenobiotic compounds and oxidative stress.
      The aim of this study was to determine the relationship among GST gene
      expression, maternal iron intake during pregnancy, and neonatal birth weight. The
      study participants were 1087 Korean gravidas and their newborns recruited for the
      Mothers and Children's Environmental Health study between 2006 and 2010. A 24-h
      dietary recall interview was conducted to estimate iron intake; additional intake
      through nutritional supplements was thoroughly investigated. Deletion
      polymorphisms of GSTM1 and GSTT1 were genotyped using PCR. Dietary iron
      consumption during pregnancy was positively associated with birth weight in
      pregnant women who were GSTM1-present after adjustment for the following
      covariates: maternal age, prepregnancy BMI, mother's education level, log
      transformed urinary cotinine level, infant gender, gestational age at term, log
      transformed energy intake, parity, and the use of folic acid supplements (P <
      0.05). There were interactions between the GSTM1 genotype and iron intakes from
      animal foods (P < 0.05), diet (P < 0.05), and diet with supplements (P < 0.05).
      No relationship was found between maternal iron intake and birth weight for the
      GSTT1 polymorphism. This study demonstrates that increased iron consumption
      during pregnancy may improve infant birth weight for mothers who are GSTM1
      present, but it might not be beneficial for mothers with the GSTM1-null genotype.

PMID- 23173170
TI  - Low-methoxyl pectin stimulates small intestinal mucin secretion irrespective of
      goblet cell proliferation and is characterized by jejunum Muc2 upregulation in
      rats.
AB  - Generally, soluble fibers increase small intestinal mucin secretion by increasing
      the number of goblet cells in a viscosity-dependent manner. The present study
      aimed to examine the mechanism by which low-methoxyl pectin (LPC) affects mucin
      secretion in the small intestine. First, diets containing 50 g/kg of low
      viscosity fiber (LPC, gum arabic, guar gum, low-molecular konjac mannan,
      arabinogalactan, sodium alginate) or high-molecular konjac mannan (KMH) were fed
      to Wistar rats for 10 d. Luminal mucin was greater in the LPC and KMH groups than
      in the fiber-free control group, but only the KMH group had more goblet cells in
      the ileum compared with the other groups. Next, Sprague-Dawley rats were fed LPC,
      KMH, or high-methoxyl pectin (HPC) diets (50 g/kg) for 10 d. The KMH and LPC
      groups, but not the HPC group, had greater luminal mucin than the control group,
      whereas jejunum Muc2 expression was higher only in the LPC group. Sprague-Dawley
      rats fed the LPC diet for 1 or 3 d had greater luminal mucin and jejunum Muc2
      expression than those fed the control diet. In vitro studies using HT-29MTX cells
      showed that, of the various fibers studied, only LPC and HPC affected mucin
      secretion. Finally, Wistar rats were fed the LPC diet with or without neomycin in
      drinking water for 10 d; neomycin treatment did not compromise the effect of LPC
      on mucin secretion. We conclude that LPC does not affect the number of goblet
      cells but can interact directly with the epithelium and stimulate small
      intestinal mucin secretion.

PMID- 23173171
TI  - Accounting for an isobaric interference allows correct determination of folate
      vitamers in serum by isotope dilution-liquid chromatography-tandem MS.
AB  - Mild and prolonged oxidative degradation of 5-methyltetrahydrofolate (5
      methylTHF) leads to the biologically inactive pyrazino-s-triazine derivative of
      4alpha-hydroxy-5-methylTHF (MeFox). MeFox and the biologically active 5
      formyltetrahydrofolate (5-formylTHF) are isobaric compounds that behave similarly
      during chromatographic and mass separation, making coelution and
      misidentification likely. Our published routine liquid chromatography-tandem MS
      (LC-MS/MS) method did not discern between 5-formylTHF and MeFox, measuring the
      sum of these compounds at a mass to charge ratio (m/z) of 474->327 as 5
      formylTHF. We modified this method to separate MeFox and 5-formylTHF by either
      chromatography or unique mass transitions and then applied the 2 methods to serum
      specimens to determine typical concentrations of these compounds. The 2 unique
      transitions (m/z: 5-formylTHF, 474->299; MeFox, 474->284) showed good sensitivity
      [limit of detection (nmol/L): 5-formylTHF, 0.21; MeFox, 0.34], selectivity (no
      interfering peaks), spiking recovery (mean +/- SD: 5-formylTHF, 103 +/- 3.4%;
      MeFox, 94 +/- 10%), and low imprecision (CV: 5-formylTHF, 3.9% at 2.4 nmol/L;
      MeFox, 5.1% at 2.9 nmol/L). The mass separation method detected 5-formylTHF in
      the same specimens as the chromatographic separation method. Analysis of several
      thousand serum specimens showed that the majority (~85%) contained MeFox at <3
      nmol/L but no detectable 5-formylTHF concentrations, some (~14%) contained 5
      formylTHF at <0.5 nmol/L, and a few specimens contained 5-formylTHF at >1 nmol/L
      and MeFox at >10 nmol/L. In summary, serum can contain 5-formylTHF high enough to
      contribute to total folate and contains MeFox that will bias total folate if not
      appropriately separated. Including measurements of MeFox and 5-formylTHF along
      with the other folate vitamers will enhance assessments of the association
      between biologically active folate and health effects.

PMID- 23173172
TI  - Association between dairy food consumption and risk of myocardial infarction in
      women differs by type of dairy food.
AB  - The relation between dairy foods, particularly specific foods, and risk of
      cardiovascular disease (CVD) remains unclear. We examined the association between
      total, as well as specific, dairy food intakes and incidence of myocardial
      infarction (MI) in a prospective population-based cohort. We followed 33,636
      women (aged 48-83 y), free from CVD, cancer, and diabetes at baseline (1997), in
      the Swedish Mammography Cohort. Consumption of milk, cultured milk/yogurt,
      cheese, cream, creme fraiche, and butter was obtained from a validated self
      administered FFQ at baseline. We used Cox proportional hazards regression models
      to estimate HRs and 95% CIs, adjusted for relevant CVD risk factors. MI incidence
      was ascertained from national registries. Over 11.6 y of follow-up, we
      ascertained 1392 cases of MI. When the highest quintile was compared with the
      lowest quintile, total dairy food intake was inversely associated with MI risk
      [multivariable adjusted HR: 0.77 (95% CI: 0.63, 0.95)]. Among specific dairy food
      products, total cheese was inversely associated [HR: 0.74 (95% CI: 0.60, 0.91)]
      and butter used on bread but not on cooking was positively associated [HR: 1.34
      (95% CI: 1.02, 1.75)] with MI risk. Other specific dairy food products were not
      significantly associated with MI risk. No differences were observed between
      consumption of specific low-fat and high-fat dairy foods, expressed as either
      absolute intakes or intakes relative to the total, and MI risk. Failure to
      consider dairy foods as a heterogeneous group in future studies could hamper
      important insights of relevance for the development of dietary guidelines.

PMID- 23173173
TI  - Thiamine nutritional status and depressive symptoms are inversely associated
      among older Chinese adults.
AB  - Thiamine has been hypothesized to play an important role in mental health;
      however, few studies have investigated the association between thiamine
      nutritional status and depression in the general population. Concentrations of
      free thiamine and its phosphate esters [thiamine monophosphate (TMP) and thiamine
      diphosphate (TDP)] in erythrocytes were measured by HPLC among 1587 Chinese men
      and women aged 50-70 y. The presence of depressive symptoms was defined as a
      Center for Epidemiological Studies Depression Scale score of >=16. The median
      erythrocyte concentration (nmol/L) was 3.73 for free thiamine, 3.74 for TMP, and
      169 for TDP. The overall prevalence of depressive symptoms was 11.3%. Lower
      concentrations of all 3 erythrocyte thiamine biomarkers were monotonically
      associated with a higher prevalence of depressive symptoms: the multivariable
      adjusted ORs comparing the lowest with the highest quartiles were 2.97 (95% CI =
      1.87, 4.72; P-trend < 0.001) for free thiamine, 3.46 (95% CI = 1.99, 6.02; P
      trend < 0.001) for TMP, and 1.98 (95% CI = 1.22, 3.21; P-trend = 0.002) for TDP.
      In conclusion, poorer thiamine nutritional status and higher odds of depressive
      symptoms were associated among older Chinese adults. This finding should be
      further investigated in prospective or interventional studies.

PMID- 23173174
TI  - Functional characterization of the chicken fatty acid elongases.
AB  - The health benefits of the (n-3) PUFA, EPA, and DHA have created a demand for
      fish and fish oil, the main sources of these PUFA. Production animals, such as
      poultry, are potential alternate and sustainable sources of EPA and DHA, provided
      these fatty acids can be synthesized from plant-derived alpha-linolenic acid
      [ALA, 18:3(n-3)]. Because elongases are potential control points in the
      conversion of ALA to DHA in rats, we examined the chicken elongases, ELOVL2 and
      ELOVL5, which had not been characterized. ELOVL2 activity was limited to C20-22
      PUFA substrates and the major product of ELOVL2 metabolism of EPA was 24:5(n-3).
      This indicates that ELOVL2 can sequentially elongate EPA to docosapentaenoic acid
      [DPA, 22:5(n-3)] and then onto 24:5(n-3). ELOVL5 selectivity was broader with
      elongation of C18-22 PUFA substrates. The ability of chicken ELOVL5 to
      efficiently synthesize 24:5(n-3) is unique compared with ELOVL5 enzymes from
      other species. The expression of ELOVL5 was higher than ELOVL2 in livers of
      broiler chickens and their expression did not change when dietary ALA was
      increased from 0.6 to 1.3% of dietary energy for 42 d. The expression of both
      genes was higher than previously seen in rats. The chicken elongase enzymes are
      unlike those of any species studied to date, because both ELOVL2 and ELOVL5 have
      the ability to efficiently elongate DPA. In addition, the relative abundance of
      ELOVL2 and ELOVL5 in the liver suggests that chickens may be able to metabolize
      more DPA through to 24:5(n-3), the precursor of DHA, compared with other species
      such as rats.

PMID- 23173175
TI  - Recent applications of engineered animal antioxidant deficiency models in human
      nutrition and chronic disease.
AB  - Dietary antioxidants are essential nutrients that inhibit the oxidation of
      biologically important molecules and suppress the toxicity of reactive oxygen or
      nitrogen species. When the total antioxidant capacity is insufficient to quench
      these reactive species, oxidative damage occurs and contributes to the onset and
      progression of chronic diseases, such as neurodegenerative diseases,
      cardiovascular diseases, and cancer. However, epidemiological studies that
      examine the relationship between antioxidants and disease outcome can only
      identify correlative associations. Additionally, many antioxidants also have
      prooxidant effects. Thus, clinically relevant animal models of antioxidant
      function are essential for improving our understanding of the role of
      antioxidants in the pathogenesis of complex diseases as well as evaluating the
      therapeutic potential and risks of their supplementation. Recent progress in gene
      knockout mice and virus-based gene expression has potentiated these areas of
      study. Here, we review the current genetically modified animal models of dietary
      antioxidant function and their clinical relevance in chronic diseases. This
      review focuses on the 3 major antioxidants in the human body: vitamin C, vitamin
      E, and uric acid. We examine genetic models of vitamin C synthesis (guinea pig,
      Osteogenic Disorder Shionogi rat, Gulo(-/-) and SMP30(-/-) mouse mutants) and
      transport (Slc23a1(-/-) and Slc23a2(-/-) mouse mutants), vitamin E transport
      (Ttpa(-/-) mouse mutant), and uric acid synthesis (Uox(-/-) mouse mutant). The
      application of these models to current research goals is also discussed.

PMID- 23173176
TI  - Consumption of breakfast and the type of breakfast consumed are positively
      associated with nutrient intakes and adequacy of Canadian adults.
AB  - Few studies have assessed the associations between breakfast intake and nutrient
      adequacy [where inadequacy reflects prevalence of usual intakes below the
      estimated average requirement (EAR) and potential excess reflects the prevalence
      above the tolerable upper intake level (UL)]. This study examined associations
      among breakfast, nutrient intakes, and nutrient adequacy in Canadian adults.
      Respondents aged >=19 y in the Canadian Community Health Survey 2.2 (n = 19,913)
      were classified as breakfast nonconsumers (11%), ready-to-eat cereal (RTEC)
      breakfast consumers (20%), or other breakfast consumers (69%). Nutrient intakes
      from food (24-h recall) and the prevalence of usual intakes below the EAR and
      above the UL from food alone and from food plus supplements were compared by
      breakfast group. Usual intake distributions were estimated using the National
      Cancer Institute method. Breakfast consumers, and to a greater extent RTEC
      breakfast consumers, had significantly higher intakes of fiber and several
      vitamins and minerals than breakfast nonconsumers. Compared with nonconsumers,
      RTEC and other breakfast consumers had significantly lower prevalences below the
      EARs for vitamin A and magnesium. The prevalences below the EARs of these
      nutrients and calcium, thiamin, vitamin D, and iron were significantly lower with
      RTEC breakfasts than with other breakfasts. Similar patterns were observed from
      food alone compared with food plus supplements. Breakfast consumption did not
      affect prevalence above the UL based on food sources, although based on food plus
      supplements, breakfast consumers had slightly higher proportions that were above
      the UL than nonconsumers for several nutrients. Breakfast, especially an RTEC
      breakfast, is associated with improved nutrient adequacy and does not
      meaningfully affect prevalence above the UL.

PMID- 23173177
TI  - Plasma uric acid is associated with increased risk of type 2 diabetes independent
      of diet and metabolic risk factors.
AB  - Current evidence suggests a direct association of uric acid with diabetes risk,
      but it is still unclear whether this is independent of risk factors such as
      obesity and diet. We aimed to investigate whether plasma uric acid concentrations
      are independently associated with incident type 2 diabetes and to investigate the
      role of a uric acid-related dietary pattern in this association. We used a case
      cohort nested in the European Prospective Investigation into Cancer and Nutrition
      Netherlands study. The study included 2318 subcohort members and 845 incident
      diabetes cases, with a mean follow-up of 10 y. At baseline, blood samples were
      taken and diet was assessed using a validated FFQ. A uric acid-related dietary
      pattern was derived with reduced rank regression. Diabetes was mainly self
      reported and verified against general practitioner records. Plasma uric acid was
      (mean +/- SD) 231 +/- 54.6 MUmol/L in the subcohort. After adjustment for
      established diabetes risk factors such as age, the HR (highest vs. lowest
      quartile of uric acid) for diabetes was 4.36 (95% CI: 3.22, 5.90). Further
      adjustment for adiposity attenuated the HR to 1.86 (95% CI: 1.32, 2.62).
      Additional adjustment for hypertension and biochemical markers, such as TG,
      slightly attenuated the association [HR = 1.43 (95% CI: 0.97, 2.10)]. A uric acid
      related dietary pattern did not confound the association. In conclusion, this
      study supports that high uric acid concentrations are associated with increased
      diabetes risk, although a large part of the association can be explained by the
      degree of adiposity.

PMID- 23173178
TI  - An integrated approach to extreme thermostabilization and affinity maturation of
      an antibody.
AB  - Antibodies are important tools for a broad range of applications due to their
      high specificity and ability to recognize virtually any target molecule. However,
      in order to be practically useful, antibodies must be highly stable and bind
      their target antigens with high affinity. We present a combinatorial approach to
      generate high-affinity, highly stable antibodies through the design of stable
      frameworks, specificity grafting and maturation via somatic hypermutation in
      vitro. By collectively employing these methods, we have engineered a highly
      stable, high-affinity, full-length antibody with a T(m) over 90 degrees C that
      retains significant activity after heating to 90 degrees C for 1 h, and has ~95
      fold improved antigen-binding affinity. The stabilized IgG framework is
      compatible with affinity maturation, and should provide a broadly useful scaffold
      for grafting a variety of complementarity-determining region loops for the
      development of stable antibodies with desired specificities.

PMID- 23173179
TI  - Rearranging and concatenating a native RTX domain to understand sequence
      modularity.
AB  - The use of repetitive peptide sequences forming predictable secondary structures
      has been a key paradigm in recent efforts to engineer biomolecular recognition.
      The modularity and predictability of these scaffolds enables precise
      identification and mutation of the active interface, providing a level of control
      which non-repetitive scaffolds often lack. However, the majority of these
      scaffolds are well-folded stable structures. If the structures had a stimulus
      responsive character, this would enable the allosteric regulation of their
      function. The calcium-responsive beta roll-forming repeats in toxin (RTX) domain
      potentially offer both of these properties. To further develop this scaffold, we
      synthesized a set of RTX peptides ranging in size from 5 to 17 repeats, with and
      without C-terminal capping. We found that while the number of repeats can be
      altered to tune the size of the RTX face, repeat ordering and C-terminal capping
      are critical for successful folding. Comparing all of the constructs, we also
      observed that native configuration with nine repeats exhibited the highest
      affinity for calcium. In addition, we performed a comparison on a set of known
      RTX-containing proteins and find that C-terminal repeats often possess deviations
      from the consensus RTX sequence which may be essential for proper folding. We
      further find that there seems to be a narrow size range in which RTX domains
      exist. These results demonstrate that the deviations from the consensus RTX
      sequence that are observed in natural proteins are important for high-affinity
      calcium binding and folding. Therefore, the RTX scaffolds will be less modular as
      compared with other, non-responsive scaffolds, and the sequence-dependent
      interactions between different repeats will need to be retained in these
      scaffolds as they are developed in future protein-engineering efforts.

PMID- 23173180
TI  - The European HANDOVER Project: a multi-nation program to improve transitions at
      the primary care--inpatient interface.

PMID- 23173181
TI  - The Handover Toolbox: a knowledge exchange and training platform for improving
      patient care.
AB  - BACKGROUND: Safe and effective patient handovers remain a global organisational
      and training challenge. Limited evidence supports available handover training
      programmes. Customisable training is a promising approach to improve the quality
      and sustainability of handover training and outcomes. OBJECTIVE: We present a
      Handover Toolbox designed in the context of the European HANDOVER Project. The
      Toolbox aims to support physicians, nurses, individuals in health professions
      training, medical educators and handover experts by providing customised handover
      training tools for different clinical needs and contexts. METHODS: The Handover
      Toolbox uses the Technology Enhanced Learning Design Process (TEL-DP), which
      encompasses user requirements analysis; writing personas; group concept mapping;
      analysis of suitable software; plus, minus, interesting rating; and usability
      testing. TEL-DP is aligned with participatory design approaches and ensures
      development occurs in close collaboration with, and engagement of, key
      stakeholders. RESULTS: Application of TEL-DP confirmed that the ideal formats of
      handover training differs for practicing professionals versus individuals in
      health profession education programmes. Training experts from different countries
      differed in their views on the optimal content and delivery of training. Analysis
      of suitable software identified ready-to-use systems that provide required
      functionalities and can be further customised to users' needs. Interest rating
      and usability testing resulted in improved usability, navigation and uptake of
      the Handover Toolbox. CONCLUSIONS: The design of the Handover Toolbox was based
      on a carefully led stakeholder participatory design using the TEL-DP approach.
      The Toolbox supports a customisable learning approach that allows trainers to
      design training that addresses the specific information needs of the various
      target groups. We offer recommendations regarding the application of the Handover
      Toolbox to medical educators.

PMID- 23173182
TI  - Context, culture and (non-verbal) communication affect handover quality.
AB  - BACKGROUND: Transfers of care, also known as handovers, remain a substantial
      patient safety risk. Although research on handovers has been done since the
      1980s, the science is incomplete. Surprisingly few interventions have been
      rigorously evaluated and, of those that have, few have resulted in long-term
      positive change. Researchers, both in medicine and other high reliability
      industries, agree that face-to-face handovers are the most reliable. It is not
      clear, however, what the term face-to-face means in actual practice. OBJECTIVES:
      We studied the use of non-verbal behaviours, including gesture, posture, bodily
      orientation, facial expression, eye contact and physical distance, in the
      delivery of information during face-to-face handovers. METHODS: To address this
      question and study the role of non-verbal behaviour on the quality and accuracy
      of handovers, we videotaped 52 nursing, medicine and surgery handovers covering
      238 patients. Videotapes were analysed using immersion/crystallisation methods of
      qualitative data analysis. A team of six researchers met weekly for 18 months to
      view videos together using a consensus-building approach. Consensus was achieved
      on verbal, non-verbal, and physical themes and patterns observed in the data.
      RESULTS: We observed four patterns of non-verbal behaviour (NVB) during
      handovers: (1) joint focus of attention; (2) 'the poker hand'; (3) parallel play
      and (4) kerbside consultation. In terms of safety, joint focus of attention was
      deemed to have the best potential for high quality and reliability; however, it
      occurred infrequently, creating opportunities for education and improvement.
      CONCLUSIONS: Attention to patterns of NVB in face-to-face handovers coupled with
      education and practice can improve quality and reliability.

PMID- 23173183
TI  - Fragmented care in the era of limited work hours: a plea for an explicit handover
      curriculum.
AB  - The current challenge in surgical residency education, preserving a sense of
      accountability in an era of limited work hours and multiple transitions of care,
      can be accomplished through the promotion of effective handovers. Approaches
      include increasing the transparency of handovers, enhancing the 'situational
      awareness' of individuals involved, and incorporating narratives and social
      interactions, and expanding common ground among professionals who collectively
      have responsibility for patient care. Done well, handovers can preserve the
      physician-patient relationship and provide a continuity bridge during a
      vulnerable time for patients.

PMID- 23173184
TI  - Technology support of the handover: promoting observability, flexibility and
      efficiency.
AB  - BACKGROUND: Efforts to standardise data elements and increase the
      comprehensiveness of information included in patient handovers have produced a
      growing interest in augmenting the verbal exchange of information with written
      communications conducted through health information technology (HIT). OBJECTIVE:
      The aim of this perspective is to offer recommendations to optimise technology
      support of handovers, based on a review of the relevant scientific literature.
      RECOMMENDATIONS: Review of the literature on human factors and the study of
      communication produced three recommendations. The first entails making available
      "shared knowledge" relevant to the handover and subsequent clinical management
      with intended and unintended recipients. The second is to create a flexible
      narrative structure (unstructured text fields) for human-human communications
      facilitated by technology. The third recommendation is to avoid reliance on real
      time data entry during busy periods. Implementing these recommendations is
      anticipated to increase the observability (the ability to readily determine
      current status), flexibility, and efficiency of HIT-supported patient handovers.
      CONCLUSIONS: Anticipated benefits of technology-supported handovers include
      reducing reliance on human memory, increasing the efficiency and structure of the
      verbal exchange, avoiding readbacks of numeric data, and aiding clinical
      management following the handover. In cases when verbal handovers are delayed, do
      not occur, or involve members of the health care team without first-hand access
      to critical information, making 'common ground' observable for all recipients,
      creating a flexible narrative structure for communication and avoiding reliance
      on real-time data entry during the busiest times has implications for HIT design
      and day to day data entry and management operations. Benefits include increased
      observability, flexibility, and efficiency of HIT-supported patient handovers.

PMID- 23173185
TI  - The patient handover as an entrustable professional activity: adding meaning in
      teaching and practice.

PMID- 23173186
TI  - Neurofibromatosis Type 1 and pancreatic islet cell tumours: an association which
      should be recognized.

PMID- 23173187
TI  - Edaravone, a novel free radical scavenger, prevents steroid-induced osteonecrosis
      in rabbits.
AB  - OBJECTIVE: To investigate the efficacy of edaravone, a novel free radical
      scavenger, on preventing steroid-induced osteonecrosis (ON) in a rabbit model.
      METHODS: Thirty-six New Zealand white rabbits were divided into control (C; n =
      6), steroid-administered (S; n = 15) and edaravone-administered groups (E; n =
      15) after receiving an established protocol of steroid-induced ON. Before and
      after steroid administration, plasma levels of reduced glutathione (GSH) and
      lipid peroxidation (LPO) were measured for oxidative stress. Two weeks later
      bilateral proximal femurs were dissected for micro-CT-based micro-angiography,
      and the presence or absence of ON and intravascular thrombi were examined
      histopathologically. Immunohistochemical examination of oxidative injury in bone
      tissue was conducted using the anti-8-hydoxy-2'-deoxyguanosine and anti
      malondialdehyde mAbs. RESULTS: The incidence of ON in the E group (20%) was
      significantly lower than in the S group (73%). Three to five days after steroid
      administration, the plasma GSH level was significantly higher and LPO level was
      significantly lower in the E group than the S group. Compared with the S group,
      there were significantly more small-sized perfusion vessels and fewer large-sized
      dilated vessels in the E group. Thrombosis incidence was significantly lower in
      the E group than the S group. Intraosseous vessels and haematopoietic cells that
      sustained oxidative injury were significantly fewer in the E group than the S
      group. CONCLUSION: Edaravone exerted beneficial effects on reducing incidence of
      steroid-induced ON by suppressing the accumulation of lipid peroxidative products
      and oxidative DNA damage in endothelial cells and haematopoietic cells.

PMID- 23173188
TI  - Increased serum vascular cell adhesion molecule (VCAM)-1 levels in patients with
      erosive hand osteoarthritis.

PMID- 23173189
TI  - Experimentally increased noise levels change spatial and singing behaviour.
AB  - The reasons why animal populations decline in response to anthropogenic noise are
      still poorly understood. To understand how populations are affected by noise, we
      must understand how individuals are affected by noise. By modifying the acoustic
      environment experimentally, we studied the potential relationship between noise
      levels and both spatial and singing behaviour in the European robin (Erithacus
      rubecula). We found that with increasing noise levels, males were more likely to
      move away from the noise source and changed their singing behaviour. Our results
      provide the first experimental evidence in a free ranging species, that not
      merely the presence of noise causes changes in behaviour and distribution, but
      that the level of noise pollution plays a crucial role as well. Our results have
      important implications for estimating the impact of infrastructure which differs
      in the level of noise produced. Thus, governmental planning bodies should not
      only consider the physical effect on the landscape when assessing the impact of
      new infrastructure, but also the noise levels emitted, which may reduce the loss
      of suitable habitats available for animals.

PMID- 23173190
TI  - Marine trophic diversity in an anadromous fish is linked to its life-history
      variation in fresh water.
AB  - We used carbon and nitrogen stable isotopes from muscle tissues accrued in the
      ocean to examine whether marine foraging tactics in anadromous sockeye salmon
      (Oncorhynchus nerka) are linked to their ultimate freshwater life history as
      adults. Adults from large-bodied populations spawning in deep freshwater habitats
      had more enriched delta(15)N than individuals from small-bodied populations from
      shallow streams. Within populations, earlier maturing individuals had higher
      delta(15)N than older fish. These differences in delta(15)N suggest that the fish
      with different life histories or spawning habitats in freshwater either fed at
      different trophic positions or in different habitats in the ocean. We propose
      that, nested within interspecific diversity in the ecological attributes of
      salmon, population and life-history diversity in spawning adults is associated
      with variation in marine foraging tactics. These results further indicate that
      the trophic diversity of sockeye salmon in the ocean may be linked to trade-offs
      in ecological and evolutionary constraints they eventually experience as adults
      in freshwater ecosystems.

PMID- 23173191
TI  - Colour misbinding during motion rivalry.
AB  - When two dissimilar colours are displayed to the two eyes at overlapping retinal
      locations, binocular rivalry typically results: a fluctuating struggle for
      perceptual dominance of each eye's stimulus. We found instead that isoluminant
      counter-rotating patterns consisting of coloured and achromatic portions can
      promote an illusory colour 'misbinding', where the colours from both eyes were
      perceived within a single rotating pattern. The achromatic portion of one
      rotating pattern thus appeared to take on the colour of the other, oppositely
      rotating pattern. The results suggest that the neural mechanisms of colour
      binding can operate even while representations of the same patterns' motions are
      undergoing rivalry, and support the idea that rivalry can occur in isolation
      within the motion system.

PMID- 23173192
TI  - Wormholes record species history in space and time.
AB  - Genetic and fossil data often lack the spatial and temporal precision for tracing
      the recent biogeographic history of species. Data with finer resolution are
      needed for studying distributional changes during modern human history. Here, I
      show that printed wormholes in rare books and artwork are trace fossils of wood
      boring species with unusually accurate locations and dates. Analyses of wormholes
      printed in western Europe since the fifteenth century document the detailed
      biogeographic history of two putative species of invasive wood-boring beetles.
      Their distributions now overlap broadly, as an outcome of twentieth century
      globalization. However, the wormhole record revealed, unexpectedly, that their
      original ranges were contiguous and formed a stable line across central Europe,
      apparently a result of competition. Extension of the wormhole record, globally,
      will probably reveal other species and evolutionary insights. These data also
      provide evidence for historians in determining the place of origin or movement of
      a woodblock, book, document or art print.

PMID- 23173194
TI  - Towards a simplification of models using regression trees.
AB  - Over-parametrization in modelling is a well-known issue that makes it hard to
      identify which part of a model is responsible for a given behaviour. In line with
      that ascertainment, this work presents the outline of an empirical method to
      simplify models by decreasing the number of parameters. By using regression trees
      to classify outputs according to related input parameters, the method provides
      the modeller with an objective tool to reduce the range of the used parameters
      and, under certain conditions, to establish relations between them. Thereby, the
      complexity of the model is reduced on the basis of mathematical arguments. As an
      example, a dynamic energy budget-based model of a mesopelagic bacterial ecosystem
      is simplified using the presented method. The main benefits of such a method are
      thus highlighted: (i) more robust parameter estimations; (ii) less complex
      formulations; and (iii) fewer modelling assumptions. To conclude, the
      difficulties encountered are discussed, and several solutions are proposed to
      deal with them.

PMID- 23173193
TI  - Applications of polymeric adjuvants in studying autoimmune responses and
      vaccination against infectious diseases.
AB  - Polymers as an adjuvant are capable of enhancing the vaccine potential against
      various infectious diseases and also are being used to study the actual
      autoimmune responses using self-antigen(s) without involving any major immune
      deviation. Several natural polysaccharides and their derivatives originating from
      microbes and plants have been tested for their adjuvant potential. Similarly,
      numerous synthetic polymers including polyelectrolytes, polyesters,
      polyanhydrides, non-ionic block copolymers and external stimuli responsive
      polymers have demonstrated adjuvant capacity using different antigens. Adjuvant
      potential of these polymers mainly depends on their solubility, molecular weight,
      degree of branching and the conformation of polymeric backbone. These polymers
      have the ability not only to activate humoral but also cellular immune responses
      in the host. The depot effect, which involves slow release of antigen over a long
      duration of time, using different forms (particulate, solution and gel) of
      polymers, and enhances the co-stimulatory signals for optimal immune activation,
      is the underlying principle of their adjuvant properties. Possibly, polymers may
      also interact and activate various toll-like receptors and inflammasomes, thus
      involving several innate immune system players in the ensuing immune response.
      Biocompatibility, biodegradability, easy production and purification, and non
      toxic properties of most of the polymers make them attractive candidates for
      substituting conventional adjuvants that have undesirable effects in the host.

PMID- 23173195
TI  - Adhesion of mussel foot proteins to different substrate surfaces.
AB  - Mussel foot proteins (mfps) have been investigated as a source of inspiration for
      the design of underwater coatings and adhesives. Recent analysis of various mfps
      by a surface forces apparatus (SFA) revealed that mfp-1 functions as a coating,
      whereas mfp-3 and mfp-5 resemble adhesive primers on mica surfaces. To further
      refine and elaborate the surface properties of mfps, the force-distance profiles
      of the interactions between thin mfp (i.e. mfp-1, mfp-3 or mfp-5) films and four
      different surface chemistries, namely mica, silicon dioxide,
      polymethylmethacrylate and polystyrene, were measured by an SFA. The results
      indicate that the adhesion was exquisitely dependent on the mfp tested, the
      substrate surface chemistry and the contact time. Such studies are essential for
      understanding the adhesive versatility of mfps and related/similar adhesion
      proteins, and for translating this versatility into a new generation of coatings
      and (including in vivo) adhesive materials.

PMID- 23173197
TI  - A mathematical model of the defence mechanism of a bombardier beetle.
AB  - Previous studies of bombardier beetles have shown that some species have a
      continuous discharge while others exhibit a pulsed discharge. Here, a
      mathematical model of the defence mechanism of the bombardier beetle is developed
      and the hypothesis that almost all bombardiers' defences have some sort of cyclic
      behaviour at frequencies much higher than previously thought is put forward. The
      observation of pulses arises from secondary lower frequency cycles that appear
      for some parameter values. For realistic parameter values, the model can exhibit
      all the characteristics seen in the various species of bombardier. The
      possibility that all bombardiers have the same underlying defence mechanism gives
      weight to the theory that all bombardiers' explosive secretory mechanisms have
      diversified from a common ancestral mechanism.

PMID- 23173196
TI  - Acceleration feedback improves balancing against reflex delay.
AB  - A model for human postural balance is considered in which the time-delayed
      feedback depends on position, velocity and acceleration (proportional-derivative
      acceleration (PDA) feedback). It is shown that a PDA controller is equivalent to
      a predictive controller, in which the prediction is based on the most recent
      information of the state, but the control input is not involved into the
      prediction. A PDA controller is superior to the corresponding proportional
      derivative controller in the sense that the PDA controller can stabilize systems
      with approximately 40 per cent larger feedback delays. The addition of a sensory
      dead zone to account for the finite thresholds for detection by sensory receptors
      results in highly intermittent, complex oscillations that are a typical feature
      of human postural sway.

PMID- 23173198
TI  - Dissecting a wildlife disease hotspot: the impact of multiple host species,
      environmental transmission and seasonality in migration, breeding and mortality.
AB  - Avian influenza viruses (AIVs) have been implicated in all human influenza
      pandemics in recent history. Despite this, surprisingly little is known about the
      mechanisms underlying the maintenance and spread of these viruses in their
      natural bird reservoirs. Surveillance has identified an AIV 'hotspot' in
      shorebirds at Delaware Bay, in which prevalence is estimated to exceed other
      monitored sites by an order of magnitude. To better understand the factors that
      create an AIV hotspot, we developed and parametrized a mechanistic transmission
      model to study the simultaneous epizootiological impacts of multi-species
      transmission, seasonal breeding, host migration and mixed transmission routes. We
      scrutinized our model to examine the potential for an AIV hotspot to serve as a
      'gateway' for the spread of novel viruses into North America. Our findings
      identify the conditions under which a novel influenza virus, if introduced into
      the system, could successfully invade and proliferate.

PMID- 23173199
TI  - Finite element modelling versus classic beam theory: comparing methods for stress
      estimation in a morphologically diverse sample of vertebrate long bones.
AB  - Classic beam theory is frequently used in biomechanics to model the stress
      behaviour of vertebrate long bones, particularly when creating intraspecific
      scaling models. Although methodologically straightforward, classic beam theory
      requires complex irregular bones to be approximated as slender beams, and the
      errors associated with simplifying complex organic structures to such an extent
      are unknown. Alternative approaches, such as finite element analysis (FEA), while
      much more time-consuming to perform, require no such assumptions. This study
      compares the results obtained using classic beam theory with those from FEA to
      quantify the beam theory errors and to provide recommendations about when a full
      FEA is essential for reasonable biomechanical predictions. High-resolution
      computed tomographic scans of eight vertebrate long bones were used to calculate
      diaphyseal stress owing to various loading regimes. Under compression, FEA values
      of minimum principal stress (sigma(min)) were on average 142 per cent (+/-28%
      s.e.) larger than those predicted by beam theory, with deviation between the two
      models correlated to shaft curvature (two-tailed p = 0.03, r(2) = 0.56). Under
      bending, FEA values of maximum principal stress (sigma(max)) and beam theory
      values differed on average by 12 per cent (+/-4% s.e.), with deviation between
      the models significantly correlated to cross-sectional asymmetry at midshaft (two
      tailed p = 0.02, r(2) = 0.62). In torsion, assuming maximum stress values
      occurred at the location of minimum cortical thickness brought beam theory and
      FEA values closest in line, and in this case FEA values of tau(torsion) were on
      average 14 per cent (+/-5% s.e.) higher than beam theory. Therefore, FEA is the
      preferred modelling solution when estimates of absolute diaphyseal stress are
      required, although values calculated by beam theory for bending may be acceptable
      in some situations.

PMID- 23173200
TI  - The effect of sexual harassment on lethal mutation rate in female Drosophila
      melanogaster.
AB  - The rate by which new mutations are introduced into a population may have far
      reaching implications for processes at the population level. Theory assumes that
      all individuals within a population have the same mutation rate, but this
      assumption may not be true. Compared with individuals in high condition, those in
      poor condition may have fewer resources available to invest in DNA repair,
      resulting in elevated mutation rates. Alternatively, environmentally induced
      stress can result in increased investment in DNA repair at the expense of
      reproduction. Here, we directly test whether sexual harassment by males, known to
      reduce female condition, affects female capacity to alleviate DNA damage in
      Drosophila melanogaster fruitflies. Female gametes can repair double-strand DNA
      breaks in sperm, which allows manipulating mutation rate independently from
      female condition. We show that male harassment strongly not only reduces female
      fecundity, but also reduces the yield of dominant lethal mutations, supporting
      the hypothesis that stressed organisms invest relatively more in repair
      mechanisms. We discuss our results in the light of previous research and suggest
      that social effects such as density and courtship can play an important and
      underappreciated role in mediating condition-dependent mutation rate.

PMID- 23173201
TI  - Aphids evolved novel secreted proteins for symbiosis with bacterial endosymbiont.
AB  - Aphids evolved novel cells, called bacteriocytes, that differentiate specifically
      to harbour the obligatory mutualistic endosymbiotic bacteria Buchnera aphidicola.
      The genome of the host aphid Acyrthosiphon pisum contains many orphan genes that
      display no similarity with genes found in other sequenced organisms, prompting us
      to hypothesize that some of these orphan genes are related to lineage-specific
      traits, such as symbiosis. We conducted deep sequencing of bacteriocytes mRNA
      followed by whole mount in situ hybridizations of over-represented transcripts
      encoding aphid-specific orphan proteins. We identified a novel class of genes
      that encode small proteins with signal peptides, which are often cysteine-rich,
      that are over-represented in bacteriocytes. These genes are first expressed at a
      developmental time point coincident with the incorporation of symbionts strictly
      in the cells that contribute to the bacteriocyte and this bacteriocyte-specific
      expression is maintained throughout the aphid's life. The expression pattern
      suggests that recently evolved secretion proteins act within bacteriocytes,
      perhaps to mediate the symbiosis with beneficial bacterial partners, which is
      reminiscent of the evolution of novel cysteine-rich secreted proteins of
      leguminous plants that regulate nitrogen-fixing endosymbionts.

PMID- 23173202
TI  - Source population characteristics affect heterosis following genetic rescue of
      fragmented plant populations.
AB  - Understanding the relative importance of heterosis and outbreeding depression
      over multiple generations is a key question in evolutionary biology and is
      essential for identifying appropriate genetic sources for population and
      ecosystem restoration. Here we use 2455 experimental crosses between 12
      population pairs of the rare perennial plant Rutidosis leptorrhynchoides
      (Asteraceae) to investigate the multi-generational (F(1), F(2), F(3)) fitness
      outcomes of inter-population hybridization. We detected no evidence of
      outbreeding depression, with inter-population hybrids and backcrosses showing
      either similar fitness or significant heterosis for fitness components across the
      three generations. Variation in heterosis among population pairs was best
      explained by characteristics of the foreign source or home population, and was
      greatest when the source population was large, with high genetic diversity and
      low inbreeding, and the home population was small and inbred. Our results
      indicate that the primary consideration for maximizing progeny fitness following
      population augmentation or restoration is the use of seed from large, genetically
      diverse populations.

PMID- 23173203
TI  - Seed dispersal networks in the Galapagos and the consequences of alien plant
      invasions.
AB  - Alien plants are a growing threat to the Galapagos unique biota. We evaluated the
      impact of alien plants on eight seed dispersal networks from two islands of the
      archipelago. Nearly 10 000 intact seeds from 58 species were recovered from the
      droppings of 18 bird and reptile dispersers. The most dispersed invaders were
      Lantana camara, Rubus niveus and Psidium guajava, the latter two likely
      benefiting from an asynchronous fruit production with most native plants, which
      facilitate their consumption and spread. Lava lizards dispersed the seeds of 27
      species, being the most important dispersers, followed by small ground finch, two
      mockingbirds, the giant tortoise and two insectivorous birds. Most animals
      dispersed alien seeds, but these formed a relatively small proportion of the
      interactions. Nevertheless, the integration of aliens was higher in the island
      that has been invaded for longest, suggesting a time-lag between alien plant
      introductions and their impacts on seed dispersal networks. Alien plants become
      more specialized with advancing invasion, favouring more simplified plant and
      disperser communities. However, only habitat type significantly affected the
      overall network structure. Alien plants were dispersed via two pathways: dry
      fruited plants were preferentially dispersed by finches, while fleshy fruited
      species were mostly dispersed by other birds and reptiles.

PMID- 23173204
TI  - Expansion of the antimicrobial peptide repertoire in the invasive ladybird
      Harmonia axyridis.
AB  - The harlequin ladybird beetle Harmonia axyridis has emerged as a model species in
      invasion biology because of its strong resistance against pathogens and
      remarkable capacity to outcompete native ladybirds. The invasive success of the
      species may reflect its well-adapted immune system, a hypothesis we tested by
      analysing the transcriptome and characterizing the immune gene repertoire of
      untreated beetles and those challenged with bacteria and fungi. We found that
      most H. axyridis immunity-related genes were similar in diversity to their
      counterparts in the reference beetle Tribolium castaneum, but there was an
      unprecedented expansion among genes encoding antimicrobial peptides and proteins
      (AMPs). We identified more than 50 putative AMPs belonging to seven different
      gene families, and many of the corresponding genes were shown by quantitative
      real-time RT-PCR to be induced in the immune-stimulated beetles. AMPs with the
      highest induction ratio in the challenged beetles were shown to demonstrate broad
      and potent activity against Gram-negative bacteria and entomopathogenic fungi.
      The invasive success of H. axyridis can therefore be attributed at least in part
      to the greater efficiency of its immune system, particularly the expansion of AMP
      gene families and their induction in response to pathogens.

PMID- 23173205
TI  - Ecological traits affect the response of tropical forest bird species to land-use
      intensity.
AB  - Land-use change is one of the main drivers of current and likely future
      biodiversity loss. Therefore, understanding how species are affected by it is
      crucial to guide conservation decisions. Species respond differently to land-use
      change, possibly related to their traits. Using pan-tropical data on bird
      occurrence and abundance across a human land-use intensity gradient, we tested
      the effects of seven traits on observed responses. A likelihood-based approach
      allowed us to quantify uncertainty in modelled responses, essential for applying
      the model to project future change. Compared with undisturbed habitats, the
      average probability of occurrence of bird species was 7.8 per cent and 31.4 per
      cent lower, and abundance declined by 3.7 per cent and 19.2 per cent in habitats
      with low and high human land-use intensity, respectively. Five of the seven
      traits tested affected the observed responses significantly: long-lived, large,
      non-migratory, primarily frugivorous or insectivorous forest specialists were
      both less likely to occur and less abundant in more intensively used habitats
      than short-lived, small, migratory, non-frugivorous/insectivorous habitat
      generalists. The finding that species responses to land use depend on their
      traits is important for understanding ecosystem functioning, because species'
      traits determine their contribution to ecosystem processes. Furthermore, the loss
      of species with particular traits might have implications for the delivery of
      ecosystem services.

PMID- 23173206
TI  - Ecological selection as the cause and sexual differentiation as the consequence
      of species divergence?
AB  - Key conceptual issues about speciation go unanswered without consideration of non
      mutually exclusive factors. With tests based on speciation theory, we exploit the
      island distribution and habitat differences exhibited by the Caribbean cricket
      Amphiacusta sanctaecrucis, and with an analysis of divergent ecological
      selection, sexually selected differentiation and geographical isolation, address
      how these different factors interact. After testing for divergent selection by
      comparing neutral genetic and morphological divergence in one ecological
      (mandible shape) and one sexual (male genitalia shape) trait, we examine whether
      ecological or sexual selection is the primary mechanism driving population
      divergence. We find that all three factors--isolation, ecological and sexual
      selection--contribute to divergence, and that their interaction determines the
      stage of completeness achieved during the speciation process, as measured by
      patterns of genetic differentiation. Moreover, despite the striking diversity in
      genitalic shapes across the genus Amphiacusta, which suggests that sexual
      selection drives speciation, the significant differences in genitalia shape
      between forest habitats revealed here implies that ecological divergence may be
      the primary axis of divergence. Our work highlights critical unstudied aspects in
      speciation-differentiating the cause from the consequence of divergence-and
      suggests avenues for further disentangling the roles of natural and sexual
      selection in driving divergence in Amphiacusta.

PMID- 23173207
TI  - Rapid action in the Palaeogene, the relationship between phenotypic and taxonomic
      diversification in Coenozoic mammals.
AB  - A classic question in evolutionary biology concerns the tempo and mode of lineage
      evolution. Considered variously in relation to resource utilization, intrinsic
      constraints or hierarchic level, the question of how evolutionary change occurs
      in general has continued to draw the attention of the field for over a century
      and a half. Here we use the largest species-level phylogeny of Coenozoic fossil
      mammals (1031 species) ever assembled and their body size estimates, to show that
      body size and taxonomic diversification rates declined from the origin of
      placentals towards the present, and very probably correlate to each other. These
      findings suggest that morphological and taxic diversifications of mammals
      occurred hierarchically, with major shifts in body size coinciding with the birth
      of large clades, followed by taxonomic diversification within these newly formed
      clades. As the clades expanded, rates of taxonomic diversification proceeded
      independently of phenotypic evolution. Such a dynamic is consistent with the
      idea, central to the Modern Synthesis, that mammals radiated adaptively, with the
      filling of adaptive zones following the radiation.

PMID- 23173209
TI  - With that diet, you will go far: trait-based analysis reveals a link between
      rapid range expansion and a nitrogen-favoured diet.
AB  - Recent global change has had a substantial influence on the distribution of
      organisms, and many species are currently expanding their ranges. To evaluate the
      underlying processes, long-term data with good geographic resolution are
      essential. One important but generally overlooked data source is offered by the
      taxon-specific national catalogues of first provincial records that are kept in
      many countries. Here, we use such data to quantify trait-based influences on
      range expansion in Swedish butterflies and moths between 1973 and 2010. Of 282
      species meeting pre-defined quality criteria, 170 expanded their northern range
      margin, with a mean expansion rate of 2.7 km per year. The analyses demonstrate
      that habitat and diet generalists, forest species and species active during warm
      conditions have expanded their ranges more rapidly than other species. Notably,
      range expansion in diet specialists was positively related to a nitrogen-favoured
      larval diet, an effect not found among oligo- or polyphagous species. In contrast
      to the general view, this shows that specialist species can undergo rapid range
      expansion. We suggest that increased areas of nitrogen-rich habitat, and
      increased availability of a nitrogen-favoured diet, are among the most important
      drivers of range expansions, potentially having far-reaching consequences for a
      wide variety of organisms.

PMID- 23173208
TI  - Linking brains and brawn: exercise and the evolution of human neurobiology.
AB  - The hunting and gathering lifestyle adopted by human ancestors around 2 Ma
      required a large increase in aerobic activity. High levels of physical activity
      altered the shape of the human body, enabling access to new food resources (e.g.
      animal protein) in a changing environment. Recent experimental work provides
      strong evidence that both acute bouts of exercise and long-term exercise training
      increase the size of brain components and improve cognitive performance in humans
      and other taxa. However, to date, researchers have not explored the possibility
      that the increases in aerobic capacity and physical activity that occurred during
      human evolution directly influenced the human brain. Here, we hypothesize that
      proximate mechanisms linking physical activity and neurobiology in living species
      may help to explain changes in brain size and cognitive function during human
      evolution. We review evidence that selection acting on endurance increased
      baseline neurotrophin and growth factor signalling (compounds responsible for
      both brain growth and for metabolic regulation during exercise) in some mammals,
      which in turn led to increased overall brain growth and development. This
      hypothesis suggests that a significant portion of human neurobiology evolved due
      to selection acting on features unrelated to cognitive performance.

PMID- 23173210
TI  - Are elder siblings helpers or competitors? Antagonistic fitness effects of
      sibling interactions in humans.
AB  - Determining the fitness consequences of sibling interactions is pivotal for
      understanding the evolution of family living, but studies investigating them
      across lifetime are lacking. We used a large demographic dataset on preindustrial
      humans from Finland to study the effect of elder siblings on key life-history
      traits. The presence of elder siblings improved the chances of younger siblings
      surviving to sexual maturity, suggesting that despite a competition for parental
      resources, they may help rearing their younger siblings. After reaching sexual
      maturity however, same-sex elder siblings' presence was associated with reduced
      reproductive success in the focal individual, indicating the existence of
      competition among same-sex siblings. Overall, lifetime fitness was reduced by
      same-sex elder siblings' presence and increased by opposite-sex elder siblings'
      presence. Our study shows opposite effects of sibling interactions depending on
      the life-history stage, and highlights the need for using long-term fitness
      measures to understand the selection pressures acting on sibling interactions.

PMID- 23173211
TI  - Rain reverses diel activity rhythms in an estuarine teleost.
AB  - Activity rhythms are ubiquitous in nature, and generally synchronized with the
      day-night cycle. Several taxa have been shown to switch between nocturnal and
      diurnal activity in response to environmental variability, and these relatively
      uncommon switches provide a basis for greater understanding of the mechanisms and
      adaptive significance of circadian (approx. 24 h) rhythms. Plasticity of activity
      rhythms has been identified in association with a variety of factors, from
      changes in predation pressure to an altered nutritional or social status. Here,
      we report a switch in activity rhythm that is associated with rainfall. Outside
      periods of rain, the estuarine-associated teleost Acanthopagrus australis was
      most active and in shallower depths during the day, but this activity and depth
      pattern was reversed in the days following rain, with diurnality restored as
      estuarine conductivity and turbidity levels returned to pre-rain levels. Although
      representing the first example of a rain-induced reversal of activity rhythm in
      an aquatic animal of which we are aware, our results are consistent with
      established models on the trade-offs between predation risk and foraging
      efficiency.

PMID- 23173213
TI  - Comparison of clinical and physics scoring of PET images when image
      reconstruction parameters are varied.
AB  - In this study the quantitative and qualitative image quality (IQ) measurements
      with clinical judgement of IQ in positron emission tomography (PET) were
      compared. The limitations of IQ metrics and the proposed criteria of
      acceptability for PET scanners are discussed. Phantom and patient images were
      reconstructed using seven different iterative reconstruction protocols. For each
      reconstructed set of images, IQ was scored based both on the visual analysis and
      on the quantitative metrics. The quantitative physics metrics did not rank the
      reconstruction protocols in the same order as the clinicians' scoring of
      perceived IQ (R(s)=-0.54). Better agreement was achieved when comparing the
      clinical perception of IQ to the physicist's visual assessment of IQ in the
      phantom images (R(s)=+0.59). The closest agreement was seen between the
      quantitative physics metrics and the measurement of the standard uptake values
      (SUVs) in small tumours (R(s)=+0.92). Given the disparity between the clinical
      perception of IQ and the physics metrics a cautious approach to use of IQ
      measurements for determining suspension levels is warranted.

PMID- 23173212
TI  - Oxytocin-like receptors mediate pair bonding in a socially monogamous songbird.
AB  - Although many species form socially monogamous pair bonds, relevant neural
      mechanisms have been described for only a single species, the prairie vole
      (Microtus ochrogaster). In this species, pair bonding is strongly dependent upon
      the nonapeptides oxytocin (OT) and vasopressin, in females and males,
      respectively. Because monogamy has evolved many times in multiple lineages, data
      from additional species are required to determine whether similar peptide
      mechanisms modulate bonding when monogamy evolves independently. Here we test the
      hypothesis that OT-like receptor activation is required for pair bond formation
      in the socially monogamous zebra finch (Taeniopygia guttata). Males and females
      were administered chronic intracerebroventricular infusions of saline or an OT
      receptor antagonist and were observed twice daily for 3 days in a colony
      environment. A variety of affiliative, aggressive and other behaviours were
      quantified. The antagonist produced significant and selective effects on pair
      bonding (latency to pair; number of sessions paired; stable pairing) and the
      associated behaviour of allopreening. Importantly, findings for males follow the
      trends of females; this yields main effects of treatment in two-way ANOVAs,
      although within-sex analyses are significant only for females. These data provide
      evidence for both convergent evolution and species diversity in the
      neuroendocrine mechanisms of pair bonding.

PMID- 23173214
TI  - Survey of compliance with European acceptability criteria for HVL and AEC.
AB  - Half value layer (HVL) was measured for 226 general radiographic X-ray tube
      assemblies at 80 kV and for 53 dental X-ray tube assemblies at 70 kV, and
      evaluated by the previous (1997) and the new draft of European acceptability
      criteria (2009) for HVL as adopted from the IEC collateral standards. Fourteen
      per cent of the tested general radiography X-ray tube assemblies were subject to
      readjustment by the new criteria. In routine quality control tests, receptor
      entrance dose was estimated for 54 AEC systems by using post-exposure mAs values,
      taking into account the measured tube output at different tube potentials, HVL
      and estimated scattering for 10, 15 and 21 cm PMMA phantom. Receptor dose (third
      quartile) varied from 6.4 MUGy at 60 kV to 3.8 MUGy at 125 kV. The results
      correspond well to the draft criteria for maximum receptor dose of 10 MUGy and
      for the patient thickness compensation.

PMID- 23173215
TI  - EANM perspective.
AB  - Two scientific committees (physics & dosimetry) of the European Association of
      Nuclear Medicine (EANM) commented on the draft 'Radiation Protection 162:
      radiation criteria for acceptability of radiological equipment used in diagnostic
      radiology, nuclear medicine and radiotherapy' (RP 162). This document updates and
      extends the acceptability criteria mentioned in 'Radiation Protection 91' and is
      an important means to further improve the quality of medical procedures involving
      ionising radiation. While the EANM committees support the presented framework as
      described in the introductory chapter, they have suggested substantial changes to
      the specific suspension levels for nuclear medicine equipment. During the
      revision process, an agreed consensus position was reached. The EANM considers RP
      162 a significant improvement of RP 91 and endorses the document.

PMID- 23173216
TI  - Criteria for acceptability of medical radiological equipment in Euratom
      legislation.
AB  - The treaty establishing the European Atomic Energy Community ('Euratom Treaty')
      is binding primary law for 27 member states of the European Union (EU) with about
      500 million inhabitants. Council Directive 96/29/Euratom is a secondary EU law
      establishing the Basic Safety Standards (BSS) for protection of the health of
      workers and the general public. The BSS Directive is supplemented by other
      binding instruments, medical exposure being regulated under Council Directive
      97/43/Euratom ('Medical Exposures Directive', MED). MED, Article 8 (3),
      stipulates that the EU member states shall adopt criteria of acceptability for
      medical radiological equipment in order to indicate when action is necessary,
      including taking the equipment out of service. A few years ago, the European
      Commission ('the Commission', EC) started a revision of the Euratom BSS
      encompassing, among others, a codification of similar legal acts including MED.
      The draft legal proposal contains a number of changes on medical exposure and,
      while no amendments have been made on the criteria for acceptability, some of
      them (e.g. those concerning the requirements for equipment in use and the
      involvement of the medical physics expert) may have a direct influence in this
      area. The Commission submitted the revised Directive to the Council of the
      European Union in September 2011; the adoption depends on the procedures in the
      Council. In order to facilitate the implementation of MED, Article 8 (3), in 1997
      the Commission published 'Radiation Protection 91: Criteria for acceptability of
      radiological (including radiotherapy) and nuclear medicine installations'; an
      update of RP 91 was launched in 2007 and planned for publication in early 2012
      (as RP 162).

PMID- 23173217
TI  - The effect of a combined tube current modulation system on dose delivered to
      patients undergoing thoracic and abdominal CT with a 128-slice scanner.
AB  - Combined tube current modulation techniques (such as Care Dose4D used in this
      study) during computed tomography (CT) procedures bring together the benefits of
      the angular and z-axis modulation techniques, measuring X-ray attenuation profile
      in the z-axis together with the data from the perpendicular x-y direction with a
      sophisticated algorithm. The purpose of this study was to investigate the
      radiation dose, in terms of computed tomography dose index (CTDI(vol)), delivered
      to patients during thoracic and abdominal CT using this technique and compare it
      with the corresponding CTDI(vol) of the fixed tube current CT technique. The
      results revealed a 5-32% dose reduction for chest CT and a dose reduction of 7.6
      60% for the three-sequence abdominal CT scan of normal and overweight patients.
      In the case of obese patients a 15.4-18.7% dose increase for chest CT and a (
      1.5) - (26.3)% dose increase for the three-stage abdominal examinations for
      females and males, respectively, was revealed.

PMID- 23173218
TI  - Scene setting: criteria for acceptability and suspension levels in diagnostic
      radiology, nuclear medicine and radiotherapy.
AB  - The EC (European Commission) Directive on radiation protection of patients
      requires that Criteria for Acceptability of Equipment in Diagnostic Radiology,
      Nuclear Medicine and Radiotherapy be established throughout the member states.
      This paper reviews the background to this requirement and to its implementation
      in practice. It notes parallel requirements in the EC medical devices directive
      and International Electrotechnical Commission standards. It is also important to
      be aware and that both sets of requirements should ideally be harmonised due to
      the global nature of the equipment industry. The paper further reviews the type
      of criteria that can be well applied for the above purposes, and defines
      qualitative criteria and suspension levels suitable for application. Both are
      defined and relationships with other acceptance processes are considered
      (including acceptance testing at the time of purchase, commissioning and the
      issue of second-hand equipment). Suspension levels are divided into four types,
      A, B, C and D, depending on the quality of evidence and consensus on which they
      are based. Exceptional situations involving, for example, new or rapidly evolving
      technology are also considered. The publication and paper focuses on the role of
      the holder of the equipment and related staff, particularly the medical physics
      expert and the practitioner. Advice on how the criteria should be created and
      implemented and how this might be coordinated with the supplier is provided for
      these groups. Additional advice on the role of the regulator is provided.

PMID- 23173219
TI  - Experience with the European quality assurance guidelines for digital mammography
      systems in a national screening programme.
AB  - The transition to a fully digital breast screening programme, utilising three
      different full-field digital mammography (FFDM) systems has presented many
      challenges to the implementation of the European guidelines for physico-technical
      quality assurance (QA) testing. An analysis of the QA results collected from the
      FFDM systems in the screening programme over a 2-y period indicates that the
      three different systems have similar QA performances. Generally, the same tests
      were failed by all systems and failure rates were low. The findings provide some
      assurance that the QA guidelines are being correctly implemented. They also
      suggest that there is more scope for the development of the relevance of the
      guidelines with respect to modern FFDM systems. This study has also shown that a
      summary review of the QA data can be achieved by simple organisation of the QA
      data storage and by automation of data query and retrieval using commonly
      available software.

PMID- 23173220
TI  - Criteria and suspension levels in diagnostic radiology.
AB  - The EC (European Council) Directive on radiation protection of patients requires
      that criteria for acceptability of equipment in diagnostic radiology, nuclear
      medicine and radiotherapy be established throughout the member states. This study
      reviews the background to this requirement and to its implementation in practice.
      It notes and considers parallel requirements in the EC medical devices directive
      and International Electrotechnical Commission standards that it is also important
      to consider and that both sets of requirements should ideally be harmonised due
      to the global nature of the equipment industry. The study further reviews the
      types of criteria that can be well applied for the above purposes, and defines
      qualitative criteria and suspension levels suitable for application. Both are
      defined and relationships with other acceptance processes are considered
      (including acceptance testing at the time of purchase, commissioning and the
      issue of second-hand equipment). Suspension levels are divided into four types,
      A, B, C and D, depending on the quality of evidence and consensus they are based
      on. Exceptional situations involving, for example, new or rapidly evolving
      technology are also considered. The publication and paper focuses on the role of
      the holder of the equipment and related staff, particularly the medical physics
      expert and the practitioner. Advice on how the criteria should be created and
      implemented is provided for these groups and how this might be coordinated with
      the supplier. Additional advice on the role of the regulator is provided.

PMID- 23173221
TI  - Employing various blood pressure measurements yields valuable data.  Measures of
      aortic blood pressure and pulse wave velocity provide additional information on
      arterial stiffness and vascular health.

PMID- 23173222
TI  - Stem cell research shows promise for heart failure patients.  Though it remains
      years away from wide clinical practice, stem cell therapy continues to offer
      encouraging glimpses at future heart disease care.

PMID- 23173223
TI  - Exercise plays a key role in treating heart disease. Studies show that regular
      physical activity can improve cardiovascular risk factors such as weight,
      arterial health, blood pressure and cholesterol.

PMID- 23173224
TI  - Revascularization is a viable option for older patients, too. Research shows
      patients 80 and older have higher survival rates when heart attacks are treated
      with bypasses or percutaneous coronary interventions.

PMID- 23173225
TI  - Device designed to prevent strokes gets widespread use.  Cleveland Clinic doctors
      developed a method of reducing blood clot formation in the left atrial appendage
      of the heart.

PMID- 23173226
TI  - I'm 67 and I've been a runner for many years. I was recently diagnosed with high
      blood pressure, which runs in my family. I take two medications for it, but we're
      still trying to get the right combination to get it under control. Can I continue
      running and how will know if I'm overdoing it?

PMID- 23173227
TI  - How much does the cholesterol in your diet affect the cholesterol levels in the
      blood?  I'm curious because I eat a diet that is lower in cholesterol than my
      husband, but my LDL cholesterol level is much higher.

PMID- 23173228
TI  - I'm having a stent put in one of my coronary arteries soon and I wonder how long
      I will need to be on clopidogrel.  Does it depend on the kind of stent?

PMID- 23173229
TI  - United approach to foot-and-mouth disease.

PMID- 23173230
TI  - A good death--naturally?

PMID- 23173231
TI  - Editor's note: promotion is key.

PMID- 23173232
TI  - Re: ineffective therapies.

PMID- 23173233
TI  - Re: a new name for the holistic SIG.

PMID- 23173234
TI  - Re: stockpersons assume veterinary role on live export voyages. Response from
      Mark Schipp.

PMID- 23173235
TI  - Re: stockpersons assume veterinary role on live export voyages. Response from
      Kevin Doyle.

PMID- 23173236
TI  - Re: stockpersons assume veterinary role on live export voyages. Response from
      Paul Nilon.

PMID- 23173237
TI  - [Superficial thrombophlebitis, unjustly underestimated disease--has the time come
      to change our views?].

PMID- 23173238
TI  - [Splenectomy and sepsis: the patient must be informed of the risk, he must be
      vaccinated and in certain cases use antibiotics prophylactically].

PMID- 23173240
TI  - [Leptospirosis].

PMID- 23173239
TI  - [Is it possible decrease the number of serious infections after splenectomy?].

PMID- 23173241
TI  - [Day hospital].

PMID- 23173242
TI  - [Interview with Lia Ricon on day hospital].

PMID- 23173243
TI  - The most effective way of delivering a train-the-trainers program: a systematic
      review.
AB  - INTRODUCTION: Previous literature has shown that multifaceted, interactive
      interventions may be the most effective way to train health and social care
      professionals. A Train-the-Trainer (TTT) model could incorporate all these
      components. We conducted a systematic review to determine the overall
      effectiveness and optimal delivery of TTT programs. METHODS: We searched 15
      databases. Reference lists and online resources were also screened. Studies with
      an objective follow-up measure collected over 1 week after the intervention were
      included. The intervention had to be based on a TTT model for health and social
      care professionals. RESULTS: Eighteen studies met the inclusion criteria. TTT
      interventions varied greatly, ranging from didactic presentations to group
      discussions and role-plays. The heterogeneity of the studies and limited data
      prevented meta-analysis. A narrative review found that the TTT programs in 13
      studies helped to increase knowledge, improve clinical behavior, or produce
      better patient outcomes. One study showed no effect. Three studies showed
      possible effect and one study showed that a CD-ROM training method was more
      effective than a TTT training method in improving participants' knowledge.
      Ratings of the studies' methodologies suggested moderate risk of bias, which
      limits interpretation of the results. DISCUSSION: There is evidence that using a
      blended learning approach to deliver TTT programs--combining different techniques
      such as interactive, multifaceted methods and accompanying learning materials-
      can help to effectively disseminate and implement guidelines and curricula to
      health and social care professionals. However, further research is needed to
      determine the optimum "blend" of techniques.

PMID- 23173244
TI  - [Chinese medicine needs the baptism of science].
AB  - All branches of mature practical technologies of both Eastern and Western ancient
      cultures, such as astronomy, geography, calendar, agriculture, architectonics,
      medicine, and so on, possess their own scientific connotation, which were derived
      from gradual accumulation and repeated validation of practical experiences. The
      ancient Greek medicine has the advantage of easily receiving scientific 'baptism'
      (reformation). The ontology and logics in ancient Greek philosophy, served as the
      epistemological and methodological bases, could effectively promote the
      development of science. Therefore, following the rapid progress of natural
      sciences since the Renaissance of the West world, the ancient Greek medicine
      rationally received the scientific "baptism" and gradually transformed into
      "modern medicine". In recent years, an upsurge to study and reappraise the works
      of Galen, an outstanding doctor and philosopher of Roman Empire, was evoked to
      discover and illuminate the practical and historical values of ancient Greek
      medicine. In ancient times, the medical theories and clinical practice of both
      Greek medicine and Chinese medicine were quite similar to each other, and they
      separately produced particular merits of themselves. However, owe to lack in the
      support of natural philosophy in ancient China, the progress of Chinese medicine,
      with its original native qualities for thousands of years only showed increase of
      clinical experiences, rather than scientific reformation of its essences.
      Therefore, Chinese medicine should also receive scientific "baptism" as Greek
      medicine. Ebb tide and see the real gold. The valuable medical experiences of
      Chinese medicine can be picked up for wide application, and its great historical
      achievements can be revealed for later pondering.

PMID- 23173245
TI  - [Effects of acupuncture combined Chinese materia medica for tonifying shen and
      soothing gan on the anxiety and depression of patients with in vitro
      fertilization and embryo transplantation and on the treatment outcomes].
AB  - OBJECTIVE: To assess the effects of acupuncture combined Chinese materia medica
      for tonifying shen and soothing gan (CMMTSSG) on the anxiety and depression of
      patients with in vitro fertilization and embryo transplantation (IVF-ET), and to
      observe the treatment outcomes. METHODS: Totally 97 IVF-ET patients were randomly
      assigned to two groups, the acupuncture combined CMMTSSG (group A, 51 cases) and
      the Western medicine treatment group (group B, 46 cases). The long protocol of
      IVF-ET in a mid luteal phase was performed in all patients. Patients in group A
      received acupuncture and CMMTSSG (erzhi tiangui granule and xiaoyao granule)
      during the process of ovarian hyperstimulation, while those in group B only
      received the routines of IVF-ET. The improvement of Shen deficiency Gan
      depression syndrome (SDGDS) between after and before treatment were observed in
      the two groups. The changes of self-rating anxiety scale (SAS) and Beck
      depression inventory (BDI) score were observed. The endometrial thickness,
      typing, and endometrial blood flow resistance index (RI) on the day of injecting
      HCG, the number of retrieved oocytes, the rate of high quality oocytes, the
      fertilization rate, the rate of high quality embryos, and the clinical pregnancy
      rate were respectively compared between the two groups. RESULTS: The scores of
      SDGDS, SAS, and BDI were improved more obviously in group A than in group B,
      showing statistical difference (P < 0.01). There was no statistical difference in
      the endometrial thickness on the day of injecting HCG between the two groups (P >
      0.05). The proportion of type A endometrium was 74.5% (38/51 cases) in group A
      and 45.7% (21/46 cases) in group B, showing statistical difference between the
      two groups (P < 0.01). The RI was significantly lower in group A (0.48 +/- 0.03)
      than in group B on the day of injecting HCG (0.52 +/- 0.06, P < 0.01). There was
      no statistical difference in the number of retrieved oocytes and the
      fertilization rate between the two groups (P > 0.05). The rate of high quality
      oocyte, the rate of high quality embryos, and the clinical pregnancy rate were
      all improved more significantly in group A than in group B, showing statistical
      difference between the two groups (P < 0.05). CONCLUSIONS: Acupuncture combined
      CM-MTSSG could obviously alleviate unfavorable emotions as anxiety and depression
      in patients with IVF-ET, effectively improve the treatment outcomes. Its effects
      might be correlated with lowering the excitability of the sympathetic nervous
      system, elevating the quality of oocytes, and improving the endometrial
      receptivity.

PMID- 23173246
TI  - [Clinical observation on treatment of premature ovarian failure patients of shen
      deficiency gan stagnation syndrome by combination of bushui roumu recipe and
      medroxyprogesterone acetate tablet HUA].
AB  - OBJECTIVE: To study the therapeutic efficacy of bushui roumu recipe (BRR)
      combined medroxyprogesterone acetate tablet (MAT) in treating premature ovarian
      failure (POF). METHODS: Totally 90 POF patients of Shen deficiency Gan stagnation
      syndrome were assigned to 3 groups by random number table, 30 in each group.
      Patients in the treatment group were treated with BRR and MAT, those in the
      Chinese medicine group were treated with BRR, and those in the Western medicine
      group were treated with artificial period method. All patients were treated for 3
      months. The menstrual improvement was observed before and after treatment. The
      therapeutic efficacy was assessed using modified Kupperman scoring standard. The
      serum levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), and
      estradiol (E2) were observed before and after treatment. RESULTS: (1) In aspect
      of the menstrual improvement: In the treatment group 20 patients had menstrual
      onset during the treatment course. Ten had normal menstruation after discontinued
      medication. Of them one got pregnancy one month after treatment. In the Chinese
      medicine group 6 patients had menstrual onset during the treatment course. Two
      had normal menstruation after discontinued medication. In the Western medicine
      group 26 patients had menstrual onset during the treatment course. Twelve had
      normal menstruation after discontinued medication. Better effects on the
      menstrual improvement were obtained in the treatment group than in the Chinese
      medicine group (P < 0.01), but with no statistical difference when compared with
      the Western medicine group (P > 0.05). (2) There was statistical difference in
      modified Kupperman scores of the 3 groups between before and after treatment (P <
      0.01). The improvement of total modified Kupperman score was better in the
      treatment group than in the other two groups (P < 0.01). The improvement of
      palpitation was better in the treatment group than in the other two groups (P <
      0.05). The improvement of tidal fever and sweat was better in the treatment group
      and the Chinese medicine group than in the Western medicine group (P < 0.05). (3)
      After treatment all patients' serum E2 was higher than before treatment, serum
      levels of FSH and LH were lower than before treatment. Compared pre- and post
      treatment, there was statistical difference (P < 0.01). The serum E2 level in the
      3 groups was higher after treatment than before treatment with statistical
      difference (P < 0.01). The levels of FSH and LH were lower in the 3 groups after
      treatment than before treatment with statistical difference (P < 0.01). The
      improvement of E2 was better in the treatment group than in the Chinese medicine
      group (P < 0.05). The improvement of FSH and LH was better in the treatment group
      than in the Western medicine group (P < 0.05). CONCLUSION: Combination of BRR and
      MAT could improve the clinical symptoms, menstruation, and serum reproductive
      hormones in POF patients of Shen deficiency Gan stagnation syndrome.

PMID- 23173247
TI  - [Study on the differential gene expressions of chronic hepatitis B patients of
      gan depression pi deficiency syndrome and pi-wei damp-heat syndrome].
AB  - OBJECTIVE: To explore the differential gene expressions of chronic hepatitis B
      (CHB) of Gan depression Pi deficiency syndrome (GDPDS) and Pi-Wei damp-heat
      syndrome (PWDHS). METHODS: The ulnar venous blood was withdrawn from healthy
      subjects (26 cases), patients of GDPDS (35 cases) and PWDHS (34 cases) on an
      empty stomach. The total RNA was extracted using Trizol method. The differential
      genes were detected using Aglient expression profile chip and screened using
      randomized variance model. The results were analyzed using GO, Pathway, GeneBank,
      NCBI, and Geneontology. RESULTS: There were 125 differential genes between CHB
      patients of GDPDS and those of PWDHS (including 66 up-regulated genes and 59 down
      regulated genes), mainly involving in functions of transmembrane transport,
      response to selenium ion, and regulation of calcium ion-dependent exocytosis. The
      signal pathway participated in mainly includes cell adhesion molecules, calcium
      ion signaling pathway, leukocyte trans-endothelial migration. We present gene co
      expression networks to find 9 interactions among genes (LOC340508, HIST2H2BE,
      MPL, FLJ22536, TUBA8, NT5M, EGFL7, PTPRF, TSPAN33), which were mainly involved in
      immune response, cell growth, DNA damage, signal transduction, inflammatory
      reaction, and so on. CONCLUSIONS: The differential expression genes existed
      between CHB patients of GDPDS and those of PWDHS, indicating that Chinese
      medicine syndrome classification has its own basis for gene expression profile.
      The genomics research method is expected to provide an objective basis for
      Chinese medicine syndrome typing.

PMID- 23173248
TI  - [Study on the correlation between chronic asymptomatic HBV carriers of yin
      asthenia constitution and genotypes of HLA-DRB1 and HLA DQA1 alleles].
AB  - OBJECTIVE: To study on the correlation between chronic asymptomatic HBV carriers
      (ASC) of yin asthenia constitution and genotypes of HLA-DRB1 and HLA DQA1
      alleles. METHODS: Totally 105 ASC were assigned to two groups according to their
      constitutions, i.e., the yin asthenia group (47 cases) and the non-yin asthenia
      group (58 cases). The genotypes of HLA-DRB1 and HLA DQA1 alleles were determined
      using PCR-SSP. RESULTS: The gene frequency of HLA-DRB1 * 09 allele and HLA-DQA1 *
      0301 allele (being 12.1% and 19.1%) were obviously lower in the yin asthenia
      group than in the non-yin asthenia group (being 27.8% and 39.7%, P < 0.05). The
      gene frequency of HLA-DRB1 * 11 allele and HLA-DQA1 * 0501 allele were obviously
      higher in the yin asthenia group (being 12.1% and 28.7%) than in the non-yin
      asthenia group (4.3% and 9.5%), showing statistical difference (P < 0.05, P <
      0.01). CONCLUSIONS: HLA-DRB1 * 09 allele and HLA-DQA1 * 0301 allele might be the
      molecular bases for non-yin asthenia patients with ASC. HLA-DRB1 * 11 allele and
      HLA-DQA1 * 0501 allele might be the molecular bases for yin asthenia patients
      with ASC.

PMID- 23173249
TI  - [Efficacy observation of treating early and midterm chronic renal failure
      patients by qi supplementing, collateral dredging, detoxifying, and turbidity
      descending recipe combined with basic methods of Western medicine].
AB  - OBJECTIVE: To observe therapeutic efficacy of treating early and midterm chronic
      renal failure (CRF) patients by qi supplementing, collateral dredging,
      detoxifying, and turbidity descending recipe (QSCDDTDR) combined with basic
      methods of Western medicine (WM). METHODS: Totally 160 early and midterm CRF
      patients were recruited from Hebei Hospital of Traditional Chinese Medicine,
      Hebei Medical University from January 2007 to December 2011. They were randomly
      assigned to the treatment group and the control group, 80 in each group. On the
      basis of basic treatment of WM, QSCDDTDR was given to patients in the treatment
      group, while niaoduqing granule (NDQG) was given to those in the control group.
      After 12 months of treatment, the therapeutic efficacy, Chinese medicine (CM)
      symptom scores, serum creatinine (SCr), blood urine nitrogen (BUN), 24 h urine
      protein quantitation, hemoglobin (Hb), and the occurrence of end-point events
      were observed. RESULTS: The total effective rate in the treatment group was 77.6%
      (28/76), obviously higher than that in the control group [(58.1%, 43/74), P <
      0.05]. After treatment the CM syndrome scores obviously decreased in the
      treatment group (18.3 +/- 5.3), obviously lower than before treatment (26.0 +/-
      4.4) and the control group (22.4 +/- 4.9) (P < 0.05, P < 0.01). The levels of
      SCr, BUN, and 24 h urine protein quantitation were (169.1 +/- 22.6) micromol/L,
      (10.4 +/- 2.0) mmol/L, (861.4 +/- 232.7) mg/24 h, respectively, in the treatment
      group after treatment, which were lower than before treatment [(204.1 +/- 27.7)
      micromol/L, (13.2 +/- 3.2) mmol/L, (1 287.5 +/- 442.3) mg/24 h, P < 0.01). The
      aforesaid indices were also improved in the control group after treatment (P <
      0.05, P < 0.01). The decrease in SCr, BUN, and 24 h urine protein quantitation
      after treatment was more obviously in the treatment group than in the control
      group [(185.8 +/- 23.9) micromol/L, (11.2 +/- 2.5) mmol/L, (1014.5 +/- 301.7)
      mg/24 h; P < 0.05, P < 0.01). The incidence rate of the end-point events was
      10.53% (8/76) in the treatment group and 13.51% (10/74) in the control group, but
      with no statistical difference. CONCLUSION: QSCDDTDR combined with basic methods
      of WM showed better therapeutic efficacy in improving the renal function and
      reducing the level of urinary protein of the early and midterm CRF patients.

PMID- 23173250
TI  - [Effects of rhubarb on the intestinal barrier function of patients with acute
      myocardial infarction-heart].
AB  - OBJECTIVE: To clarify the intestinal barrier function (IBF) state of patients
      with acute myocardial infarction-heart failure (AMI-HF), and to compare the
      therapeutic effects of rhubarb and Pantoprazole (proton pump inhibitor). METHODS:
      Enrolled were 107 AMI patients from ICU, Union Hospital, Tongji Medical College,
      Huazhong University of Science and Technology from May 2008 to April 2010. Of
      them, 47 AMI patients without HF were recruited as the control group, while 60
      AMI-HF patients were randomly assigned to the rhubarb group (30 cases, treated by
      rhubarb + Pantoprazole) or the Pantoprazole group (30 cases, treated by
      Pantoprazole + routine treatment). All patients were treated till the 14th day of
      the onset. The fecal occult blood (FOB) test was performed daily. The occurrence
      of the digestive tract hemorrhage on the 14th day after onset was compared. The N
      terminal pro-brain natriuretic peptide (NT-proBNP), serum D-lactic acid, plasma
      glutamine (Gln), endotoxin and cytokines [high sensitive C reaction protein
      (hsCRP), tumor necrosis factor-alpha (TNF-alpha), interleukin-10 (IL-10)], and
      heart function were compared among the three groups before and after treatment.
      RESULTS: There was no statistical difference in the case number of using aspirin,
      clopidogel, low molecular weight heparin, ACEI/ARB, statins, insulin, and
      antibiotics among the 3 groups. The case number of using beta-blocker was
      obviously lower in the two medication groups than in the control group (P <
      0.05). The case number of using diuretics was obviously higher in the two
      medication groups than in the control group (P < 0.05). There was no statistical
      difference in the incidence of digestive tract hemorrhage (P = 0.413). Compared
      with the control group before treatment, Gln and ejection fraction (EF) were both
      lowered, NT-proBNP, D-lactic acid, endotoxin, hsCRP, TNF-alpha, and IL-10
      increased in the two medication groups (P < 0.01). There was no statistical
      difference in each index between the two medication groups (P > 0.05). Compared
      with before treatment, NT-proBNP, D-lactic acid, endotoxin, hsCRP, TNF-alpha, and
      IL-10 decreased in the Pantoprazole group (P < 0.01), and no obvious change in
      Gin or EF was found (P > 0.05). Gin and EF increased in the rhubarb group after
      treatment, and they were higher than those of the control group. Blood NT-proBNP,
      D-lactic acid, endotoxin, hsCRP, TNF-alpha, and IL-10 decreased in the rhubarb
      group after treatment, showing statistical difference when compared with the
      control group (P < 0.01, P < 0.05). CONCLUSIONS: Impaired IBF and endotoxemia
      existed in AMI-HF patients. Rhubarb not only could prevent the digestive tract
      hemorrhage, but also could reduce endotoxemia, inhibit inflammatory reactions,
      and improve the heart function through ameliorating the IBF.

PMID- 23173251
TI  - [Efficacy assessment of treating patients with coronary heart disease angina of
      phlegm and stasis mutual obstruction syndrome by Danlou tablet].
AB  - OBJECTIVE: To assess the clinical efficacy of danlou tablet (DT) in treating
      coronary heart disease angina (CHDA) patients of phlegm and stasis mutual
      obstruction syndrome (PSMOS). METHODS: Totally 66 CHDA patients of PSMOS were
      recruited from four centers (Beijing Guang'anmen Hospital, Beijing Anzhen
      Hospital, First Affiliated Hospital of Henan College of Traditional Chinese
      Medicine, and Hubei Union Hospital). They were assigned to two groups according
      to the random digit table, the treatment group (treated by DT +Western medicine)
      and the control group (treated by Western medicine), 33 in each group. All
      patients took Western medicine. Patients in the treatment group were given DT,
      1.5 g each time, twice daily, while those in the control group took DT placebo.
      The treatment course was 28 days for all. The efficacy of angina, the angina
      attack frequency, its duration, the score of angina, the numbers of ST segment
      depression and flat or inversed T wave, the lead number of inversed T wave, the
      angina relief time after taking nitroglycerin, the amount of nitroglycerin were
      observed in the two groups. The changes of Chinese medicine (CM) syndrome scores,
      including the duration and frequency of chest tightness and pain, shortness of
      breath, fatigue, palpitation, spontaneous sweating, and total syndrome score were
      compared before and after treatment. The changes of hypersensitive C-reactive
      protein (hs-CRP), homocysteic acid (HCY), soluble CD40 ligand (sCD40L),
      interleukin-6 (IL-6), myeloperoxidase (MPO), matrix metalloproteinase-9 (MMP-9),
      and vascular cell adhesion molecular-1 (VCAM-1) were also observed in both
      groups. RESULTS: The total effective rate was significantly higher in the
      treatment group (26/32 cases, 81.2%) when compared with the control group (13/30
      cases, 43.3%, P < 0.05). Compared with before treatment in the same group, the
      duration and frequency of chest tightness and pain, the score of angina, the
      numbers of ST segment depression and flat or inversed T wave, the lead number of
      inversed T wave, the angina relief time after taking nitroglycerin, the amount of
      nitroglycerin, the duration and frequency of chest tightness and pain, hs-CRP,
      sCD40L, HCY, IL-6, MMP-9, MPO were lowered after treatment in both groups (P <
      0.01, P < 0.05). The VCAM-1 level decreased in the treatment group, while it
      increased in the control group, showing statistical difference (P < 0.01, P <
      0.05). Compared with the control group after treatment, the duration and
      frequency of chest tightness and pain, the score of angina, the angina relief
      time after taking nitroglycerin, the amount of nitroglycerin, the duration and
      frequency of chest tightness and pain, fatigue, the total syndrome score, the
      levels of hs-CRP, sCD40L, HCY, IL-6, MMP-9, MPO, and VCAM-1 were lowered in the
      treatment group after treatment (P < 0.01, P < 0.05). CONCLUSION: DT could
      improve CHDA patients' clinical symptoms, inhibit the inflammation reaction,
      showing plaque stabilizing and anti-oxidization effects.

PMID- 23173252
TI  - [Acupuncture therapy for the improvement of sleep quality of outpatients
      receiving methadone maintenance treatment: a randomized controlled trial].
AB  - OBJECTIVE: To study the efficacy and safety of acupuncture therapy for the
      improvement of sleep quality of outpatients receiving methadone maintenance
      treatment (MMT). METHODS: Using randomized double-blinded controlled design,
      seventy-five MMT outpatients with low sleep quality [score of Pittsburgh sleep
      quality index (PSQI) > or = 8], were randomly assigned to the acupuncture group
      (38 cases) and the sham-acupuncture group (37 cases). All patients maintained
      previous MMT. Acupuncture was applied to Baihui (GV20), Shenmen (bilateral, TF4),
      Shenting (GV24), Sanyinjiao (bilateral, SP6), and Sishencong (EX-HN1) in the
      acupuncture group. The same procedures were performed in the sham-acupuncture
      group, but not to the acupoints (5 mm lateral to the acupoints selected in the
      acupuncture group) with shallow needling technique. The treatment was performed 5
      times each week for 8 successive weeks. The PSQI was assessed before treatment,
      at the end of the 2nd, 4th, 6th, and 8th week of the treatment. The detection
      ratio of low sleep quality and the incidence of adverse acupuncture reactions
      were compared between the two groups at the end of the 8th week. RESULTS: The
      overall PSQI score was obviously higher in the acupuncture group than in the sham
      acupuncture group with statistical difference (P < 0.01). The detection ratio of
      low sleep quality at the end of the 8th week was lower in the acupuncture group
      (60.53%, 23/38 cases) than in the sham-acupuncture group (83.78%, 31/37 cases)
      with statistical difference (P < 0.05). The rate of adverse acupuncture reaction
      was 5.26% (2/38 cases) in the acupuncture group and 2.70% (1/37 cases) in the
      sham-acupuncture group respectively, showing no statistical difference (P >
      0.05). CONCLUSION: Acupuncture therapy could effectively and safely improve the
      sleep quality of outpatients receiving MMT.

PMID- 23173253
TI  - [Clinical study of treating knee osteoarthritis (Bi syndrome of knee) by massage
      combined Chinese materia medica footbath fumigation and washing].
AB  - OBJECTIVE: To evaluate the clinical efficacy of treating knee osteoarthritis
      (KOA, Bi syndrome of knee) by massage combined Chinese materia medica (CMM)
      footbath fumigation and washing, and to observe the changes of the Lysholm knee
      score (LKSS). METHODS: Totally 61 patients with grade I to III KOA were randomly
      assigned to two groups, the treatment group and the control group. Patients in
      the treatment group were treated with massage combined CMM footbath fumigation
      and washing, while those in the control group were treated with oral
      administration of meloxicam. They were treated for 20 days (times). The LKSS was
      assessed before treatment, 10 days of treatment, by the end of the treatment, and
      1 month after treatment. RESULTS: (1) The therapeutic efficacy in the treatment
      group was superior to that in the control group (P < 0.05). Thirteen cases were
      clinically controlled, with 11 markedly effective, 6 effective, and 1 ineffective
      in the treatment group, while 5 cases were clinically controlled, with 11
      markedly effective, 10 effective, and 4 ineffective in the control group. (2) The
      LKSS: The post-treatment LKSS was higher than that before treatment in the two
      groups. The LKSS at 10 days (times) of treatment was lower in the treatment group
      than in the control group, but with no statistical difference (P > 0.05). The
      LKSS by the end of the treatment was higher in the treatment group than in the
      control group (P < 0.05). (3) The case number of patients in need of receiving
      the treatment again within 1-month follow-up and the difference between the LKSS
      at follow-ups and that by the end of the treatment were lower in the treatment
      group than in the control group (P < 0.01). CONCLUSION: Massage combined CMM
      footbath fumigation and washing had better clinical efficacy on patients
      suffering from KOA.

PMID- 23173254
TI  - [Effects of Ginkgo biloba extract 50 on inflammatory cytokines and glia cell
      ultrastructures in the prefrontal cortex and hippocampus of aging rats].
AB  - OBJECTIVE: To study the effects of Ginkgo biloba extract 50 (GBE50) on
      inflammatory cytokines and glia cell injury in the prefrontal cortex and
      hippocampus of aging rats and its probable mechanism. Methods Totally 45 male SD
      rats were randomly divided into 4 groups, i.e., the normal control group (n=12),
      the model group (n=11), the low dose GBE50 group (n=10), and the high dose GBE50
      group (n=12). The aging rat model was intraperitoneally injected with D-galactose
      to establish the aging model for 42 days. Starting from the 22nd day of modeling,
      rats in the low dose GBE50 group and the high dose GBE50 group were administered
      by gastrogavage with 75 mg/kg and 150 mg/kg respectively. The protein contents
      and mRNA expressions of IL-1beta, IL-6, and TNF-a in the prefrontal cortex and
      hippocampus of rats were detected by radioimmunoassay and Real-time fluorescence
      quantitative PCR assay respectively. The ultrastructural changes of glia cells in
      the hippocampal CA1 region were observed by transmission electron microscope.
      Results The protein contents and mRNA expressions of IL-1beta and TNF-alpha in
      the prefrontal cortex and the hippocampus of aging rats obviously increased when
      compared with the normal control group (P < 0.05, P < 0.01). The content of IL-6
      in the hippocampus of aging rats obviously decreased (P < 0.01). Compared with
      the model group, the protein content and mRNA expression of IL-1beta in the
      prefrontal cortex and the hippocampus were obviously downregulated in the low and
      high dose GBE50 groups. The content of TNF-alpha in the prefrontal cortex was
      obviously downregulated in the low and high dose GBE50 groups, the content of TNF
      alpha in the hippocampus was obviously downregulated in the low dose GBE50 group
      (P < 0.05, P < 0.01). The content of IL-6 in the prefrontal cortex of the low
      dose GBE50 group was up-regulated. The content of IL-6 in the hippocampus of the
      high dose GBE50 group was also upregulated. The mRNA expression of IL-6 in the
      prefrontal cortex of the low and high dose GBE50 groups obviously increased (P <
      0.05, P < 0.01). Low and high dose GBE50 showed obvious recovery on the
      ultrastructural damage of glia cells in the hippocampal CA1 region. CONCLUSIONS:
      GBE50 showed inhibitive effects on the inflammatory reaction of nerves of aging
      rats. Its mechanism might be possibly correlated with its regulatory effects on
      the cytokines in the prefrontal cortex and the hippocampus, as well as the
      ultrastructures of glia cells in the prefrontal cortex and hippocampus to some
      degree.

PMID- 23173255
TI  - [Effects of puerarin on the neurocyte apoptosis and p-Akt (Ser473) expressions in
      rats with cerebral ischemia/reperfusion injury].
AB  - OBJECTIVE: To observe the effects of puerarin (Pue) on the neurocyte apoptosis
      and the p-Akt (Ser473) expression in the ischemic penumbra of rats with cerebral
      ischemia/reperfusion (I/R). METHODS: The 48 Sprague-Dawley rats were randomly
      divided into four groups, i.e., the sham-operation group, the I/R group, the Pue
      treatment group, and the Pue + LY294002 treatment group (Pue + LY), 12 in each
      group. The cerebral I/R rat model was established by Longa's suture method. Pue
      and Pue + specific P13K kinase inhibitor, i.e., LY294002 were administered. The
      score of the neurological deficit was estimated 1 h followed by 24 h reperfusion.
      The infarct volume was measured using TTC staining. The number of apoptotic
      neurons were detected using Tunel method. The expressions of p-Akt (Ser473) was
      detected using immunohistochemical assay, and the images were analyzed. RESULTS:
      The score of the neurological deficit decreased more obviously, the number of
      apoptosis decreased more significantly, the expressions of p-Akt (Ser473)
      increased more significantly in the Pue group than in the I/R group (all P <
      0.05). The score of the neurological deficit increased more obviously, the number
      of apoptosis increased more significantly, the expression of p-Akt (Ser473)
      decreased more significantly in the Pue + LY group than in the Pue group (all P <
      0.05). CONCLUSION: Pue reduced the apoptosis of neurocytes and had protective
      effects against cerebral I/R injury possibly through activating the PI3K/Akt
      signaling pathway.

PMID- 23173256
TI  - [Effects of sodium tanshinone B on the protein expression of NMDAR1 in rat
      hippocampal subfields following focal ischemia/reperfusion injury].
AB  - OBJECTIVE To observe the changing laws of the protein expression of N-methyl D
      aspartate receptor (NMDAR) in rat hippocampal subfields following focal
      ischemia/reperfusion injury, and to study the effects of sodium tanshinone B
      (STB) on it, thus exploring the possible mechanism of STB for treating cerebral
      ischemia. METHODS: The rat model of focal cerebral ischemia/reperfusion injury
      was established using middle cerebral artery occlusion (MCAO) by reversibly
      inserting a nylon thread. The Wistar rats were randomly divided into the sham
      operation group, the I/R model group, and the low, middle, and high dose STB
      groups. The neural functional disturbance was scored referring to the 5-grade Zea
      Longa EL standard. The protein expression of NMDAR1 in the ischemic side was
      detected using immunohistochemical assay. RESULTS: There was statistical
      difference in the scores of the neural functional disturbance in the middle and
      high dose STB groups when compared with the model group (P < 0.01). Results of
      the immunohistochemical assay showed the expression of NMDAR1 in CA1 region was
      obviously higher in the I/R model group, the low and middle dose STB groups than
      in the sham-operation group (P < 0.01). The expression of NMDAR1 in CA1 region
      was obviously lower in the high dose STB group than in the I/R model group (P <
      0.01), the low (P < 0.01) and middle dose STB groups (P < 0.05). The expression
      of NMDAR1 in CA3 region was obviously higher in the low dose STB group and the
      I/R model group than in the sham-operation group, the middle and high dose STB
      groups (P < 0.01). The expression of NMDAR1 in CA3 region was obviously higher in
      the high and middle dose STB groups than in the sham-operation group (P < 0.05).
      CONCLUSIONS: STB could promote the recovery of neural functions in cerebral
      ischemia/reperfusion injury rats. STB fought against cerebral
      ischemia/reperfusion injury by lowering excitable neurotransmitter glumatic acid
      and reducing the protein expression of NMDAR1.

PMID- 23173257
TI  - [Protection mechanisms of modified danggui buxue decoction for podocytes in
      adriamycin-induced nephropathy rats].
AB  - OBJECTIVE: To study the effects of modified danggui buxue decoction (MDBD) on
      podocytes in adriamycin-induced nephropathy (DN) model rats. METHODS: SD rats
      were divided into four groups, i.e., the normal control group, the model group,
      the benazepril group, and the MDBD group. On the 7th, 28th, 42nd, and 56th day of
      modeling, the urine sample was collected to examine the dynamic changes of
      urinary albumin quantitation. The renal tissue was processed for the examinations
      under light microscope and electron microscope. The immunofluorescence of nephrin
      and podocin were detected. The expressions of the slit membrane expression
      protein in the renal tissue were further analyzed using RT-PCR and Western blot.
      RESULTS: (1) Urinary protein (UP): The UP did not obviously decrease in each
      treatment group on the 7th day, but it decreased so markedly on the 28th, 42nd,
      and 56th day. There was statistical difference in UP of the benazepril group and
      the MDBD group when compared with that of the model group (P < 0.05). The
      decrease was most obvious in the MDBD group. (2) Effects on the podocytes and the
      renal tissue: RESULTS: under light microscope and electron microscope showed,
      when compared with the model group, the proliferation of mesangial cells, the
      renal tubule-interstitial lesion, the podocyte fusion, and the expressions of
      nephrin and podocin were milder, and the urinary albumin quantitation was more
      obviously reduced in the benazepril group and the MDBD group. But the renal
      fibrosis correlated renal pathological progress also existed, indicating the
      renal lesion degree was milder but could not be reversed. (3) Results of RT-PCR
      and Western blot: Statistical difference existed in the expressions of nephrin
      and podocin between the benazepril group and the MDBD group on the 56th day, when
      compared with the model group (P < 0.05). CONCLUSION: MDBD showed therapeutic
      effects on adriamycin-induced nephropathy model rats. Its actions could be
      achieved through reducing albuminuria, inhibiting the proliferation of mesangial
      cells, attenuating the renal tubule-interstitial lesion, and protecting the
      integrity of the slit membrane structure.

PMID- 23173258
TI  - [Protective effects of chailing decoction on cyclosporine A induced chronic renal
      injury and its mechanisms].
AB  - OBJECTIVE: To observe the effects of Chailing Decoction (CD) on transforming
      growth factor-beta1 (TGF-beta1), connective tissue growth factor (CTGF), renal
      cell apoptosis and proliferation in rats with chronic cyclosporine A nephropathy
      (CCN), and to explore its possible mechanism for inhibiting renal fibrosis.
      METHODS: The CCN rat model was prepared using oral administration of cyclosporine
      A (CsA, 30 mg x kg(-1) x d(-1)). Meanwhile, they were treated with CD (3 g x kg(
      1) x d(-1)) by gastrogavage. The serum blood urea nitrogen (BUN), serum
      creatinine (SCr), and creatinine clearance rate (CCr) were measured by the end of
      the fourth week of the experiment. The kidneys were taken out on the next day.
      The degree of renal fibrosis was detected using Masson staining. The protein and
      gene expressions of TGF-beta1, and CTGF were observed using immunohistochemical
      assay and RT-PCR. The renal cell apoptosis rate and the proliferation index were
      detected by flow cytometry. RESULTS: Compared with the control group (BUN: 6.123
      +/- 0.588 mmol/L; SCr: 75.654 +/- 8.196 micromol/L; CCr: 0.539 +/- 0.169 mL/min),
      the renal function of the model group (BUN: 11.600 +/- 1.437 mmol/L; SCr: 101.985
      +/- 10.809 micromol/L; CCr: 0.272 +/- 0.060 mL/min) obviously declined (P <
      0.01). The collagen deposition in the renal interstitial area significantly
      increased. The protein and mRNA expressions of TGF-beta1, and CTGF in the tubular
      epithelial cells and the mesenchymal cells were significantly enhanced (P <
      0.01). The cell proliferation index and the apoptosis rate both increased, but
      the ratio of apoptosis to proliferation (0.317 +/- 0.059) decreased more than
      that in the control group (0.680 +/- 0.150, P < 0.01). After treatment by CD, the
      renal function (BUN: 7.340 +/- 0.857; SCr: 84.923 +/- 10.627; CCr: 0.405 +/-
      0.081) was significantly enhanced (P < 0.05, P < 0.01), the collagen deposition
      decreased, the high protein and mRNA expressions of TGF-beta1 and CTGF were down
      regulated (P < 0.01), the ratio of apoptosis to proliferation increased (0.650 +/
      0.092, P<0. 01). CONCLUSION: CD could improve the renal function of CCN model
      rats, inhibit the expressions of TGF-beta1 and CTGF, and recover the balance
      between the renal cell apoptosis and proliferation by inducing cell apoptosis and
      inhibiting cell proliferation, thus delaying the renal fibrosis process.

PMID- 23173259
TI  - [Effects of dachengqi decoction containing serum on the expressions of caveolin
      1, eNOS, and NF-kappaB in lipopolysaccharide stimulated human bronchial
      epithelial cells].
AB  - OBJECTIVE: To observe the effects of dachengqi decoction (DD) containing serum on
      the expressions of caveolin-1 (CAV-1), endothelial nitric oxide synthase (eNOS),
      and nuclear transcription factor-kappa B (NF-kappaB) in lipopolysaccharide (LPS)
      stimulated human bronchial epithelial cells (HBECs). METHODS: The DD and the DD
      containing serum were prepared. The in vitro cultured HBECs were randomly divided
      into 7 groups, i.e., the normal serum control group, the LPS intervention group,
      the low dose DD serum containing group, the middle dose DD serum containing
      group, the high dose DD serum containing group, the Western medicine control
      group, the vehicle serum control group. The effects of DD containing serum at
      different doses on the mRNA and protein expressions of CAV-1, eNOS, and NF-kappaB
      were detected using methyl thiazolyl tetrazolium (MTT) colorimetry, Real-time
      PCR, immunocytochemical assay, and Western blot. RESULTS: The mRNA and protein
      expressions of CAV-1, eNOS, and NF-kappaB at the basic levels were detected in
      the HBECs of the normal serum control group. After stimulated by LPS, the mRNA
      and protein expressions of CAV-1, eNOS, and NF-kappaB increased more
      significantly in the LPS intervention group than in the normal serum control
      group (P < 0.01), while DD containing serums at different doses all could
      suppress the mRNA and protein expressions of CAV-1, eNOS, and NF-kappaB.
      CONCLUSION: DD containing serum could inhibit the expressions of CAV-1, eNOS, and
      NF-kappaB in LPS stimulated HBECs.

PMID- 23173260
TI  - [Experimental study of jiangtang xiaozhi tablet on decreasing the levels of blood
      glucose and serum lipids in transgenic mice with diabetes mellitus].
AB  - OBJECTIVE: To observe the effects of Jiangtang Xiaozhi Tablet (JTXZT) on
      decreasing the levels of blood glucose and serum lipids in KK-Ay transgenic model
      mice with diabetes mellitus (DM). METHODS: KK-Ay transgenic mice were fed with
      high fat diet to induce DM obesity model. The C57 mice of the same age were
      recruited as the control group. Then the modeled KK-Ay mice were divided into 5
      groups, i.e., the model group, the Pioglitazone Hydrochloride Tablet treatment
      group (8 mg/kg, as the positive control group), and the high dose JTXZT group (10
      g/kg), the middle dose JTXZT group (5 g/kg), and the low dose JTXZT group (2.5
      g/kg), 11 in each group. Eight weeks was taken as one therapeutic course. All
      medicines were given by gastrogavage. The food intake and body weight were
      measured every week. The blood glucose level was determined once every 2 weeks.
      The levels of fasting blood glucose (FBG), serum lipids (TC and TG), insulin
      (INS), and leptin (Lep) were assayed 8 weeks after medication. The weight of
      liver and fat were weighed to calculate their indices. Then the adipose
      denaturalization of the liver was classified. The numbers of the pancreatic islet
      and adipocytes were respectively counted. RESULTS: Compared with the model group,
      the food intake and the body weight obviously decreased in the 3 JTXZT groups (P
      < 0.05, P < 0.01). From the 6th week, the FBG level obviously decreased in the
      high dose JTXZT group (P < 0.01). After eight successive weeks of intragastric
      administration, the levels of TG and INS obviously decreased in the 3 JTXZT
      groups (P < 0.05, P < 0.01). The Lep level somewhat decreased in the high dose
      JTXZT group (P < 0.05). The indices of the liver and fat obviously decreased and
      the number of the pancreatic islet obviously increased in the 3 JTXZT groups (P <
      0.05, P < 0.01). The number of adipocytes obviously decreased in the high and
      middle dose JTXZT groups (P < 0.05, P < 0.01). The liver fatty degeneration was
      obviously improved in the high dose JTXZT group (P < 0.05). CONCLUSION: JTXZT had
      obvious effects on decreasing the levels of blood glucose and serum lipids in KK
      Ay transgenic model mice with DM obesity.

PMID- 23173262
TI  - [The expressions of TNF-alpha and MMP-9 in serum and MMP-1 mRNA in the bone
      tissue in chronic obstructive pulmonary disease patients of cold dryness syndrome
      in northwest China].
AB  - OBJECTIVE: To observe the expressions of tumor necrosis factor a (TNF-alpha) and
      matrix metalloproteinase (MMP-9) in serum and matrix metalloproteinase 1 (MMP-1)
      mRNA in the bone tissue in chronic obstructive pulmonary disease (COPD) patients
      of cold dryness syndrome (CDS) in northwest China, thus providing reference for
      wholism treating COPD of CDS. METHODS: Twenty-one male Wistar rats were randomly
      divided into three groups, i.e., the normal control group, the COPD model group,
      and the COPD of CDS group, 7 in each group. The COPD model was established by
      dripping porcine pancreatic elastase (PEE) in trachea combination with cigarette
      smoking, and the COPD of CDS model was also set up by dripping PEE in trachea in
      combination with cigarette smoking and cold-dry environmental stress. Serum
      contents of TNF-alpha and MMP-9 were determined using ELISA. The MMP-1 mRNA
      expression in rats' bone tissue was detected using fluorescent quantitative PCR.
      RESULTS: Compared with the normal control group, the serum MMP-9 level obviously
      increased in the COPD of CDS group (P < 0.05). The MMP-1 mRNA expression level in
      the bone tissue of the COPD of CDS group and the COPD model group also obviously
      increased (P < 0.01, P < 0.05). The MMP-1 mRNA expression level was obviously
      higher in the COPD of CDS group than in the COPD model group (P < 0.01). There
      was no statistical difference in the serum TNF-alpha level among the three groups
      (P > 0.05). CONCLUSION: CDS could increase the serum MMP-9 level and the MMP-1
      mRNA expression in the bone tissue, which might be one of reasons for the fact
      that cold and dry environment causes more bone resorption and bone degradation in
      COPD.

PMID- 23173261
TI  - [Effects of electroacupuncture at neiguan (PC6) on c-Jun NH2-teminal kinase
      signaling pathways in hypertrophic myocardial cells].
AB  - OBJECTIVE: To study the effects of electroacupuncture (EA) at Neiguan (PC6) on c
      Jun NH2-terminal kinases (JNK) signaling pathways in hypertrophic myocardial
      cells. METHODS: Thirty female SD rats were randomly divided into three groups,
      i.e., the normal group, the model group, and the EA group, 10 in each group.
      Isoprenaline hydrochloride (ISO) injection at the daily dose of 3 mg/kg was
      subcutaneously injected for 14 days to establish the cardiac hypertrophy (CH)
      model. Rats in normal group were subcutaneously injected with an equal volume of
      normal saline. EA at Neiguan (PC6) was applied for rats in the EA group while
      modeling, once daily, for 14 successive days. The left ventricular weight index
      (LVWI) and heart weight index (HWI) were calculated in all rats. The content of
      angiotensin II (Ang II) in the cardiac muscular tissue was tested using
      radioimmunoassay. The protein expressions of JNK and phosphorated JNK (p-JNK) in
      cardiocytes were detected using Western blot. RESULTS: Compared with the normal
      group, LVWI and HWI, the Ang II content, and the expressions of JNK and p-JNK
      were significantly higher in the model group, showing statistical difference (P <
      0.01). The aforesaid indices were obviously lower in the EA group than in the
      model group with statistical difference (P < 0.05). CONCLUSIONS: EA at PC6 could
      prevent and treat CH possibly correlated with regulation of JNK signaling
      pathways. EA might play a role possibly through regulating its upstream
      neuroendocrine factors.

PMID- 23173263
TI  - [Effects of sinomenine and methotrexate on fibroblast-like synoviocytes in
      rheumatoid arthritis].
AB  - OBJECTIVE: To investigate the effects of sinomenine (SIN) and methotrexate (MTX)
      on the proliferation and apoptosis of in vitro cultured fibroblast-like
      synoviocytes (FLS) in rheumatoid arthritis (RA) patients, as well as the
      expression of osteoclast differentiation factor in FLS. METHODS: FLS were
      isolated from the synovium of RA patients and cultured in vitro. FLS were
      incubated with different concentrations of SIN and MTX respectively or combined:
      0.001, 0.010, 0.100, 1.000 mg/mL SIN; 0.001, 0.010, 0.100, 1.000 mg/mL MTX; 0.001
      mg/mL SIN + 0.001 mg/mL MTX, 0.010 mg/mL SIN + 0.010 mg/mL MTX, 0.100 mg/mL SIN +
      0.100 mg/mL MTX, 1.000 mg/mL SIN + 1.000 mg/mL MTX, namely SIN1, 2, 3, 4 groups;
      MTX1, 2, 3, 4 groups and the combination 1, 2, 3, 4 groups. The medium without
      drugs was used as a control group. There was a total of 13 groups, each group
      with 3 complex holes. MTT was applied to detect the growth of FLS. The flow
      cytometry was applied to detect the apoptosis of FLS. The expressions of FLS
      receptor activator of nuclear factor kappa B ligand (RANKL) mRNA and
      osteoprotegerin (OPG) mRNA were observed by semi-quantitative RT-PCR. RESULTS:
      Compared with the control group, RA FLS proliferation OD values of all the drug
      groups were lower (P < 0.05). The RA FLS apoptosis OD value of the combination 3
      group increased, the OPG mRNA expression increased, the expression of RANKL mRNA
      decreased with statistical difference (P < 0.05). The RA proliferation OD values
      of the SIN3 group and the MTX3 group increased when compared with the combination
      3 group (P < 0.05). CONCLUSIONS: SIN and MTX had synergistic effects in
      inhibiting FLS. This might be one of the mechanisms for inhibiting RA bone
      damage.

PMID- 23173264
TI  - [Comparison of the effects of sanjie zhentong capsule and danazol on the
      endometriosis rats].
AB  - OBJECTIVE: To compare the effects of sanjie zhentong capsule (SZC) and danazol on
      rats with endometriosis (EMT). METHODS: Totally 48 adult female Lewis rats were
      selected, 12 as the blank control group, and the rest 36 rats in the estrus cycle
      were used to establish the EMT model. After modeling they were randomly divided
      into 3 groups, i.e., the model control group, the SZC treatment group, and the
      danazol treatment group, 12 in each group. Four weeks later the focus was
      measured by a second laparotomy. The normal saline at 1 mL/day was administered
      to rats in the model control group, SZC at 86.4 mg/day to those in the SZC
      treatment group, and danazol at 7.2 mg/day to those in the danazol treatment
      group. All the treatment lasted for 4 weeks. At the end of the treatment, a third
      laparotomy was performed to measure the size of focus. The expression of
      proliferating cell nuclear antigen (PCNA) was detected using immunohistochemical
      assay. The cell apoptosis rate was detected using terminal deoxynucleotidyl
      transferase-mediated deoxy-UTP nick-end labeling (TUNEL). The concentration of
      prostaglandin E2 (PGE2) in the peritoneal fluid and the serum were detected using
      ELISA. RESULTS: There was statistical difference in the change of the focus
      volume between the SZC treatment group (-23.27 +/- 18.18) and the danazol
      treatment group (-12.28 +/- 10.04) and the model control group (13.97 +/- 7.54, P
      < 0.01). The expression of ectopic PCNA significantly decreased and the positive
      expression rate of TUNEL obviously increased in the two treatment groups when
      compared with the model control group (P < 0.05, P < 0.01). The expression of
      ectopic PCNA decreased and the positive expression rate of TUNEL increased more
      obviously in the SZC treatment group than in the danazol treatment group (P <
      0.01). The concentration of PGE2 in the peritoneal fluid and the serum was
      significantly lower in the two treatment group when compared with the model
      control group (P < 0.01). The concentration of PGE2 in the peritoneal fluid and
      the serum was significantly lower in the SZC treatment group than in the danazol
      treatment group (P < 0.01). CONCLUSIONS: SZC and danazol both could inhibit the
      focus growth in EMT rats. SZC showed better effects. It was an effective drug for
      treating EMT.

PMID- 23173265
TI  - [The difference in acknowledging the AAHRPP between China and America].
AB  - With the active encouragement of the Chinese government, all domestic clinical
      research institutes pay more attention to the human research protect program
      (HRPP) during the process of clinical trials, and actively follow the regulations
      of medical ethical practice. We could make fully preparation for the
      accreditation by the correlated international organizations only by further
      analyzing the Association for Accreditation of Human Research Protection Program
      (AAHRPP) from a whole and in each accreditation field at different levels, thus
      having a clear understanding the difference in acknowledging the difference
      between China's hospitals and America's hospitals.

PMID- 23173266
TI  - [Analysis of GRACE principle for comparative effectiveness research].
AB  - Comparative effectiveness research (CER) now is a very popular concept in the
      field of international heath care reformation. Although its contents are not
      essentially changed, it advocates a new medical idea, a policy orientation at the
      national medical system level. The European countries and America hope CER could
      initiate the construction of a new historical milestone. Although there are
      already some guidelines for the design and report of CER by authorized
      international organizations, its assessment standards have not been involved.
      Therefore, good research for comparative effectiveness (GRACE) was signed by
      International Society Pharmacoepidemiology. A series of standard rules were
      formulated on how to assess the observational studies. In this article by
      analyzing the GRACE, we hope to provide the referential standards for enforcing
      observational studies by introducing CER in the clinical studies of Chinese
      medicine.

PMID- 23173267
TI  - [The application of qi benefiting and blood activating method in thrombolytic
      therapy of acute cerebral infarction].
AB  - The thrombolytic therapy has been widely used in treating acute cerebral
      infarction (ACI), but various severe complications restrict its clinical
      application. However, Chinese medicine shows its advantages in the treatment of
      ACI after thrombolytic therapy. Qi benefiting and blood activating method is an
      important principle and mean for supporting the vital qi and removing the surplus
      evil. By using this method, its short-term and long-term efficacy could be
      improved after thrombolytic therapy.

PMID- 23173268
TI  - [Thought and clinical experiences in diagnosing and treating heart failure].

PMID- 23173269
TI  - [Syndrome and disease combination treatment of hypertensive disease].

PMID- 23173270
TI  - [Examples for syndrome and disease combination treatment of tachyarrhythmia].

PMID- 23173271
TI  - [English translation of Chinese medical formulae from the perspective of
      adaptation and alienation].

PMID- 23173272
TI  - [The application of data digging technology in Chinese medical observation and
      analysis].

PMID- 23173273
TI  - [The research progress for Chinese materia medica polysaccharides induced tumor
      apoptosis].

PMID- 23173274
TI  - [Do you recognize this dermatosis?].

PMID- 23173275
TI  - [What slows down Odinius' campaign against overweight].

PMID- 23173276
TI  - [Pruritus--just as bad as pain].

PMID- 23173277
TI  - [Is the effectiveness of beta blockers overestimated?].

PMID- 23173278
TI  - [Why is the child hoarse? (interview by Dr. Christine Starostzik)].

PMID- 23173280
TI  - [Do combinations with hydroxychloroquine help?].

PMID- 23173279
TI  - [Becoming slimmer is hard work].

PMID- 23173281
TI  - [Surgery is not the only option in Dupuytren's contracture].

PMID- 23173282
TI  - [From nodules to chords in Dupuytren's contracture].

PMID- 23173283
TI  - [Knuckle pads and therapeutic options].

PMID- 23173284
TI  - [Ledderhose's disease--an update on therapeutic options].

PMID- 23173285
TI  - [Penis deviation with or without pain in Peyronie's disease--an update].

PMID- 23173286
TI  - [Circumcision in a medical and legal perspective].

PMID- 23173287
TI  - [Suspected depression].

PMID- 23173288
TI  - [Stroke risk--atrial fibrillation].

PMID- 23173289
TI  - [Diagnosis and treatment of hepatitis C].

PMID- 23173290
TI  - [Difficult, but absolutely feasible!].

PMID- 23173291
TI  - [Febrile neutropenia in lung cancer patients].
AB  - A malignant tumor and infection have a close relation which is hard to separate.
      The differential diagnosis of the infection is necessary even at the time of the
      diagnosis of the malignant tumor. Controlling infection is another difficulty at
      the anti-cancer treatment as next step. In this report, the issues concerning the
      infection with lung cancer, especially febrile neutropenia, was argued.

PMID- 23173292
TI  - [Current status adult pertussis in Japan].
AB  - Pertussis has been prevalent among the infants in summer, however, in recent
      years, it is increasing also in the adult. The epidemiology in 2010 showed
      pertussis in the adults dominated over 50%. Although the cough in the adults
      persists for a long time comparing with the infants, the adult pertussis is easy
      to be overlooked since the symptom is not typical especially in the adults.
      Therefore, it might be lead to the outbreak in the community. Pertussis is mainly
      treated by macrolides, such as erythromycin (EM) or clarithromycin (CAM) at
      present.

PMID- 23173293
TI  - [Clinical efficacy of tosufloxacin in children with pneumonia due to Mycoplasma
      pneumoniae].
AB  - We retrospectively examined pediatric 83 patients with pneumonia due to
      Mycoplasma pneumoniae, ranging in age from 6 months to 14 years, treated with
      tosufloxacin (TFLX) for more than 3 days between October 2010 and December 2011.
      The TFLX dose was 12 mg/kg/day (maximum 360 mg/day). Seventy-eight of the 83
      children treated with this drug showed symptom amelioration, and the response
      rate to the drug was 94.0%. The remaining 5 patients showed no improvement
      despite drug administration for 3 to 6 days, and TFLX was switched to
      minocycline, which relieved symptoms. Forty-six of the 83 were given TFLX as
      initial treatment, and the remaining 37 not responding to clarithromycin (CAM)
      and azithromycin (AZM) were also treated with TFLX. This drug was effective in 41
      (89.1%) of the 46 patients initially treated with TFLX and TFLX was effective in
      all 37 (100%) patients not responding to CAM and AZM. Side effects of TFLX
      included mild diarrhea, observed in 3 patients, but no patients had joint
      symptoms or convulsions.

PMID- 23173295
TI  - [Arbekacin sulfate concentrations in peripheral lymph and in serum after
      intravenous injection: report of four cases].
AB  - Antibiotic levels in serum are commonly used to guide antibiotic therapy. The
      antibiotic levels in peripheral lymph are a more accurate reflection of the
      efficacy of antibiotic penetration into the tissues of patients with complicated
      skin and soft-tissue infections. The pharmacokinetics of arbekacin sulfate (ABK)
      in peripheral lymph after systemic administration has not been studied. Four
      patients (cases 1-4) with skin and soft-tissue infections (average age 74.3
      years, range 54 to 85) received 200 mg of ABK intravenously once a day either by
      slow bolus (5min.) or by slow infusion (60 min.). The serum concentrations
      collected 60min. after the start ofABK infusion (C60) and the peripheral lymph
      concentrations of ABK were measured. 55 min. after initiation of slow 5-min.
      bolus (case 1), C60 was 32.5l microg/mL. The daily average concentration of ABK
      in peripheral lymph after slow bolus (case 1) was 14.84 microg/mL. The ratio
      peripheral lymph on daily average/C60 was 0.46. Patients (cases 2, 3 and 4) had
      been intravenously administered ABK at an infusion time of 60 min. C60 (cases 2,
      3 and 4) were 14.10, 11.48 and 8.26 microg/mL, respectively. The daily average
      concentration of ABK in peripheral lymph after slow infusion (case 2) was 7.80
      microg/mL. The average concentrations of ABK in peripheral lymph during the third
      eight hours since slow infusion (cases 3 and 4) were 0.72 and 2.23 microg/mL. The
      ratio peripheral lymph/C60 was 0.55, 0.06 and 0.27, respectively. An increase in
      the serum peak concentration of ABK may lead to considerable elevation of the
      concentration of ABK in peripheral lymph.

PMID- 23173296
TI  - [List of approved antibacterial agents, antifungal agents, etc. in Japan from
      January to March, 2012].

PMID- 23173297
TI  - Screening family and sexual contacts of HBsAg+ persons in the Pilsen region.
AB  - THE AIM OF THE STUDY: To detect HBsAg-positive persons and to offer their family
      and sexual contacts, after screening for viral hepatitis B (VHB) markers, free
      vaccination against the infection. MATERIAL AND METHODS: In collaboration with
      laboratories, all persons with confirmed HBsAg in the Pilsen Region (549,618
      population) were prospectively detected. From these persons, the following data
      were collected: reason for examination, clinical diagnosis, and
      ethnicity/nationality. Their family and sexual contacts were screened for
      serologic markers (HBsAg, anti-HBc, anti-HBs) and vaccinated. RESULTS: Between
      1997-2005, 1,053 HBsAg+ persons were routinely detected by the laboratories in
      the Pilsen Region. The average age of the infected persons was 41.7 years (range
      0-90 years). At the time of the detection, 63.4% of the HBsAg positives were
      clinically "healthy" carriers. Within the monitored period there was a
      considerable increase in the HBsAg positivity rate among immigrants (particularly
      from Vietnam). Of 908 family and sexual contacts, 18% were positive for hepatitis
      B markers. The highest seropositivity rates (33.9% and 27.7%) were found in
      siblings and parents, respectively, of the HBsAg+ persons. So far 77.5% of the
      susceptible contacts have used the opportunity for free vaccination. CONCLUSION:
      The study has proven the importance of detecting HBsAg carriers and vaccinating
      their contacts. Special attention should be paid to immigrant families,
      particularly from Asia. Consistent vaccination of family and sexual contacts of
      HBsAg+ persons can contribute to a more rapid elimination of hepatitis B in the
      Czech Republic.

PMID- 23173294
TI  - [In vitro susceptibilities to levofloxacin and various antibacterial agents of
      12,866 clinical isolates obtained from 72 centers in 2010].
AB  - Postmarketing surveillance of levofloxacin (LVFX) has been conducted continuously
      since 1992. The present survey was performed to investigate in vitro
      susceptibility of recent clinical isolates in Japan to 30 selected antibacterial
      agents, focusing on fluoroquinolones (FQs). The common respiratory pathogens
      Streptococcus pyogenes, Streptococcus pneumoniae, Moraxella catarrhalis, and
      Haemophilus influenzae continue to show a high susceptibility to FQs. In
      contrast, widely-prevailing resistance to macrolides was markedly noted among S
      pneumoniae and S. pyogenes. Regarding H. influenzae, the prevalence of beta
      lactamase-negative ampicillin-resistant isolates has been increasing year by year
      (25.8% in 2002, 40.0% in 2004, 50.1% in 2007, and 57.9% in 2010).
      Enterobacteriaceae showed high susceptibility to FQs, however, prevalence of LVFX
      resistant Escherichia coli, including intermediate resistance, was 29.3%, showing
      an increase over time. Nevertheless, the increase in the prevalence of LVFX
      resistant E. coli isolates has slowed since 2007 (8.2% in 2000, 11.8% in 2002,
      18.8% in 2004, 26.2% in 2007, and 29.3% in 2010), suggesting the influence of
      LVFX 500 mg tablets since its approval in 2009. Another Enterobacteriaceae
      member, Klebsiella pneumoniae, showed low resistance to FQs, in contrast with E.
      coli. In methicillin-resistant Staphylococcus aureus (MRSA), the percentage of FQ
      susceptible isolates was low, at 51.6% for susceptibility to sitafloxacin, and at
      only around 10% for susceptibility to other FQs. However, methicillin-susceptible
      S. aureus (MSSA) isolates were highly susceptible to FQs, with the percentage
      ranging from 88.5% to 99.1%. The prevalence of FQs-resistant isolates in
      methicillin-resistant coagulase-negative staphylococci was higher than that in
      methicillin-susceptible coagulase-negative staphylococci, although it was lower
      than the prevalence of FQ-resistance in MRSA. The prevalence of FQs-resistant
      Pseudomonas aeruginosa isolates derived from urinary tract infections (UTIs) was
      15.4-21.3%, higher than the prevalence of 6.1-12.3% in P. aeruginosa isolates
      from respiratory tract infections (RTIs). While this trend was consistent with
      the results of previous surveillance, gradual decreases were noted in the
      prevalence of FQ-resistant P. aeruginosa isolates derived from UTIs. The
      prevalence of multidrug-resistant P. aeruginosa was 2.3% among isolates derived
      from UTIs and 0.3% among isolates from RTIs, a decrease from the results of 2007.
      Acinetobacter spp. showed high susceptibility to FQs. Imipenem-resistant
      Acinetobacter baumannii, which is currently an emerging issue, was detected at a
      prevalence of 2.4% (13 isolates). Neisseria gonorrhoeae showed a high resistance
      of 81.3-82.5%, to FQs. Ceftriaxone (CTRX) continued to show 100% susceptibility
      until 2007, but the present survey revealed the advent of resistance to CTRX in
      some clinical isolates. The result of the present survey indicated that although
      methicillin-resistant staphylococci, Enterococcus faecium, P. aeruginosa from
      UTIs, N. gonorrhoeae, and E. coli showed resistance of about 20% or more (19.5
      89.2%) against the FQs which have been used clinically for over 17 years, the
      trends observed were similar to the results of previous surveillance. While FQ
      resistance has been prevailing in E. coli, E. coli still shows more than 70%
      susceptibility to FQs. The other bacterial species maintained high susceptibility
      rates of greater than 80%, against FQs.

PMID- 23173298
TI  - [Chromosomal integration of the sixth human herpes virus (HHV-6)].
AB  - Two closely related and commonly found human herpesviruses HHV-6 A and HHV-6 B
      are classified into the sixth human herpes virus complex (HHV-6). Primary
      infection with HHV-6 often takes place in early childhood and it can be either
      asymptomatic or manifests itself as sixth disease (caused by HHV-6 B). HHV-6
      remains present in a latent form in the body with the potential for virus
      reactivation. The article points out the phenomenon of chromosomal integration of
      HHV-6 (Ci-HHV-6) which is found in about 1% of the population and, unlike the
      commonly spread HHV-6 infection, has become hereditary, with its pathological
      potential in Ci-HHV-6 DNA carriers remaining unknown. Therefore, the focus on
      clinical consequences of Ci-HHV-6 is of high relevance to the therapeutic
      strategy for patients with high HHV-6 positivity in molecular biological tests.

PMID- 23173299
TI  - [The rules for the transport of microorganisms].
AB  - Every laboratory sometimes needs to transport microbial cultures. This is done
      mostly for the purposes of the research, teaching, or reference testing, at the
      national and international level. To ensure the highest possible safety for
      humans, animals and the environment, it is necessary to follow rules relating to
      the handling and transport of bacterial or fungal cultures. The article presents
      the basic rules for the transport of microorganisms and relevant links providing
      information about the shipping of infectious substances.

PMID- 23173300
TI  - [30 years since the first AIDS cases were reported: history and the present. Part
      II].
AB  - HIV taxonomy, morphology, biophysical properties, and replication cycle as well
      as modes of HIV transmission in humans are described. State of the art laboratory
      diagnosis of HIV/AIDS, core clinical diagnostic criteria for AIDS, and AIDS
      treatment guidelines are summarized. Global HIV/AIDS epidemic and relevant
      prevention activities are discussed.

PMID- 23173301
TI  - Correlative microscopy of Purkinje cells.
AB  - The Purkinje cell and their synaptic contacts have been described using (1) light
      microsocopy, (2) transmission and scanning electron microscopy, and freeze
      etching technique, (3) conventional and field emission scanning electron
      microscopy and cryofracture methods, (4) confocal laser scanning microscopy using
      intravital stain FM64, and (5) immunocytochemical techniques for Synapsin-I, PSD9
      5, GluR1 subunit of AMPA receptors, N-cadherin, and CamKII alpha. The outer
      surface and inner content of plasma membrane, cell organelles, cytoskeleton,
      nucleus, dendritic and axonal processes have been exposed and analyzed in a three
      dimensional view. The intramembrane morphology, in bi- and three-dimensional
      views, and immunocytochemical labeling of synaptic contacts with parallel and
      climbing fibers, basket and stellate cell axons have been characterized. Freeze
      etching technique, field emission scanning microscopy and cryofracture methods,
      and GluR1 immunohistochemistry showed the morphology and localization
      ofpostsynaptic receptors. Purkinje cell shows N-cadherin and CamKII alpha
      immunoreactivity. The correlative microscopy approach provides a deeper
      understanding of structure and function of the Purkinje cell, a new three
      dimensional outer and inner vision, a more detailed study of afferent and
      intrinsic synaptic junctions, and of intracortical circuits.

PMID- 23173302
TI  - Cryopreservation of Cyrtopodium hatschbachii Pabst (Orchidaceae) immature seeds
      by encapsulation-dehydration.
AB  - The aim of the present study was to investigate the efficiency of the
      encapsulation-dehydration technique for cryopreservation of Cyrtopodium
      hastchbachii Pabst seeds. Immature seeds of this species were cryopreserved by an
      encapsulation-dehydration technique. Seeds of five immature pods, 120 days after
      pollination, were encapsulated in 3% calcium alginate matrix and pretreated in
      liquid medium supplemented with 0.08 M sucrose (24 h), 0.15 M sucrose (24 h),
      0.25 M sucrose (48 h), 0.5 M sucrose (24 h) and 0.75 M sucrose (24 h) in shaker
      at 60 rpm. Alginate beads were dehydrated 5 h in silicagel and immersed in liquid
      nitrogen for 12 h. Cryopreserved beads were thawed at 30 degrees C for 1 min,
      rehydrated using the same liquid mediums [0.75 M sucrose (24 h), 0.5 M sucrose
      (24 h), 0.25 M sucrose (48 h) and 0.15 M sucrose (24 h)] and cultivated in half
      strength Murashige & Skoog medium (1962) with the addition of 2 g/L activated
      charcoal. Sixty four percent of seeds survived and developed into acclimatized
      plants after being cryopreserved. In this work, the encapsulation-dehydration
      technique was employed for first time in Cyrtopodium hatschbachii.

PMID- 23173303
TI  - Optimization and comparison of two different 3D culture methods to prepare cell
      aggregates as a bioink for organ printing.
AB  - The ultimate goal of tissue engineering is to design and fabricate functional
      human tissues that are similar to natural cells and are capable of regeneration.
      Preparation of cell aggregates is one of the important steps in 3D tissue
      engineering technology, particularly in organ printing. Two simple methods,
      hanging drop (HD) and conical tube (CT) were utilized to prepare cell aggregates.
      The size and viability of the aggregates obtained at different initial cell
      densities and pre-culture duration were compared. The proliferative ability of
      the cell aggregates and their ability to spread in culture plates were also
      investigated. In both methods, the optimum average size of the aggregates was
      less than 500 microm. CT aggregates were smaller than HD aggregates. 5,000 cells
      per drop HD aggregates showed a marked ability to attach and spread on the
      culture surface. The proliferative ability reduced when the initial cell density
      was increased. Comparing these methods, we found that the HD method having better
      size controlling ability as well as enhanced ability to maintain higher rates of
      viability, spreading, and proliferation. In conclusion, smaller HD aggregates
      might be a suitable choice as building blocks for making bioink particles in
      bioprinting technique.

PMID- 23173304
TI  - [Category design and clinical application of esthetic clasps].
AB  - Not only can esthetic clasps removable partial dentures reserve some advantages
      that removable partial denture itself has such as non-preparation or less
      preparation and cheap price, but also can bring metal-free smile to the patients,
      which is an new effective and affordable treatment option for partial edentulism.
      This article introduced the basic concepts, principle, various types of
      estheticdesign and related clinical application.

PMID- 23173305
TI  - [Nano-scratch research of amelogenesis imperfecta teeth].
AB  - OBJECTIVE: To study the differences between amelogenesis imperfecta (AI) teeth
      and normal human (NH) teeth in wear properties. METHODS: The ultrastructure of
      the human tooth enamel from adult patient diagnosed with AI was investigated
      using atomic force microscope (AFM) and compared with the surface of normal human
      tooth enamel. The composition of tooth enamel of AI teeth and normal human teeth
      were analyzed by energydispersive X-ray spectroscopy (EDX). The properties of
      micro-friction and wear between AI teeth and normal human teeth were compared
      using nano-scratch technology and scanning electron microscope (SEM). RESULTS:
      The AI teeth were found porosity and the loosely packed hydroxyapatite was
      distributed randomly compared with normal human teeth. The amount of C was higher
      while the amount of Ca, P were lower in AI teeth than normal human teeth. The
      friction coefficient of both AI teeth and normal human teeth was increasing with
      the load increased and the friction coefficient of AI teeth was higher than
      normal human teeth with the same load. Meanwhile, the destruction of AI teeth was
      more severe than normal human teeth with the same load. CONCLUSION: The AI teeth
      has significant differences with normal human teeth on micro-structure,
      composition and micro-friction and wear properties. Thus, we need to have a
      general consideration of all these results when doing clinical restorations.

PMID- 23173306
TI  - [Screen and analysis of differentially expressed genes related to stem-like cells
      in tongue squamous cell carcinoma Tca8113 cell line].
AB  - OBJECTIVE: To screen the differentially expressed genes of stem-like cells in
      tongue squamous cell carcinoma using suppression subtractive hybridization (SSH).
      METHODS: The cells with high and low expression of aldehyde dehydrogenase(ALDHbr
      and ALDHlow) were isolated respectively from human tongue squamous cell carcinoma
      Tca8113 cell line. SSH was used to identify differentially expressed genes in
      those two groups. Positive cell clones with high/ low-expressed ALDH were
      screened randomly for the genetic sequences and function analysis by the
      bioinformatics technology. RESULTS: Total 62 differentially expressed genes were
      identified, most of which got involved in regulation of cell cycle, cellular
      differentiation and other biology activities as gene ontology (GO) analysis
      indicated. Signal pathway analysis revealed 12 pathways related to 11 genes
      changed significantly. CONCLUSION: Several potential novel biomarker candidates
      of tongue cancer stem cells were identified and they may provide important
      insights into the functions and characteristics of human tumor stem cell.

PMID- 23173307
TI  - [Early proliferation changes and differences of gene expression in human
      periodontal ligament fibroblasts subjected to tensile and compressive stress].
AB  - OBJECTIVE: The study was aimed to provide insights into cell proliferation
      ability alteration of human periodontal ligament fibroblasts (HPDLF) under two
      different types of stimulation, cyclic tensile and compressive stress, and screen
      the differentially expressed genes to have a comprehensive understanding of the
      molecular mechanism of changes in proliferation. METHODS: Primary HPDLF were
      subjected to cyclic tensile and compressive stress (0.5 Hz, 4 000 microstrain)
      for 2 h through a four-point bending strain system. After that, cell
      proliferation ability was examined by flow cytometry. Then the gene expression
      profile was investigated by microarray analysis. RESULTS: Mechanical stress
      slowed a down proliferation of cells. S phase cells and proliferation index (PI)
      decreased. Differentially expressed genes were mainly located at nucleus and
      focus in transcription factor activity related genes, and most of them were
      involved in the regulation of transcription factors. Among them, more were in
      group of compressive stress. CONCLUSION: 1) Under mechanical loading, HPDLF
      proliferation were slowed and cell cycles were arrested. 2) Cell cycle arrest and
      the slow-down proliferation, which can be viewed as an adaptation and protection
      mechanism of cells to have more time to decide how to respond to mechanical
      stimuli, and the differential gene expression reflect the behavior of cells. The
      result of the response is gene transcription changes at first, and the most
      important biological response is the nuclear transcription. 3) HPDLF are more
      sensitive to cyclic compressive stress.

PMID- 23173308
TI  - [Study of vascular endothelial growth factor and transforming growth factor beta1
      genes regulate the mineral-related genes in human cells from apical papilla].
AB  - OBJECTIVE: To clone the VEGF165 gene and to construct eucaryotic expression
      vector, investigate the effect of overexpressed VEGF165 and transforming growth
      factor beta1 (TGFbeta1) on the mineral-related genes in human cells from apical
      papilla. METHODS: Total RNA of ECV304 cell was extracted. The VEGF165 gene was
      amplified by reverse transcription-polymerase chain reaction (RT-PCR), and then
      was subcloned into eucaryotic expression vector pcDNA3.1hisA to construct the
      recombinant vector pcDNA3.1hisA-VEGF165. After being identified by digestion and
      DNA sequencing, pcDNA3.1hisA-VEGF165, and pcDNA3.1hisA-TGFbeta1 were transfected
      into human cells from apical papilla Then the efficiency of gene transfection and
      the expression of bone sialoprotein (BSP), dentin sialophosphoprotein (DSPP),
      osteocalcin (OCN), dentin matrix protein 1 (DMP1) were detected by Real-Time
      polymerase chain reaction (PCR). RESULTS: Cloned VEGF165 gene sequences and
      inserted into expression vector of the VEGF165 sequences showed 100% homology
      related to the sequence in GenBank database. VEGF165 and TGFbeta1 mRNA were
      upregulated after transfection. The expression of DSPP mRNA were significantly
      increased in each experiment group (P < 0.05). The expression of OCN mRNA were
      increased significantly in the group transfected with pcDNA3.1hisA-TGFbeta1 and
      transfected with two plasmids (P < 0.05). The expression of BSP mRNA were not
      varying (P > 0.05), while no expression of DMP1 mRNA in each experiment group.
      CONCLUSION: The recombinant eucaryotic expression vector of pcDNA3.1hisA-VEGF165
      was constructed successfully. VEGF165 and TGFbeta1 can induce the expression of
      most mineral-related genes and they may play a key role during the
      differentiation of human cells from apical papilla.

PMID- 23173309
TI  - [A quantitative glucose method by constant air pressure for evaluating the
      sealing ability of four root canal sealers].
AB  - OBJECTIVE: To introduce a modified model for quantitative testing of glucose
      microleakage by constant air pressure and evaluate the sealing ability of four
      root canal sealers including AU Plus, Roeko Seal, Cortisomol and RC Sealer.
      METHODS: Fifty-six straight maxillary anterior teetb were randomly divided into
      four experimental groups with 12 samples in each group, group A: AH Plus, group
      B: Roeko Seal, group C: Cortisomol, group D: RC Sealer, and positive and negative
      control group with 4 samples in each. After regular root preparation, samples in
      experimental groups were obturated by cold gutta-percha lateral compaction
      technique with sealers according to group description. Control groups were
      obturated with cold gutta-percha only. Through the model above, the value of
      glucose microleakage from crown to root was measured at 1, 3, 5, 7, 10, 15, 20,
      25, 30 days with the glucose oxidase-peroxidase method (GOD-POD). RESULTS: At day
      1, 3, 5, no significant difference of microleakage was found between group A and
      B (P > 0.05). The same result was also seen between group C and D. From 7 days,
      microleakage value in each experimental group gradually increased, and
      statistical difference was found between groups (P < 0.05). CONCLUSION: This new
      model using constant air pressure is easy to establish, sensitive and practical.
      Among all the sealers evaluated, polydimethylsiloxane based root canal sealer,
      Roeko Seal has the greatest sealing ability, while epoxy-amine resin based AH
      Plus is second and Zinc Oxide based Cortisomol and RC Sealer have the least
      sealing ability.

PMID- 23173310
TI  - [The intercellular communication condition of alveolar bone with traumatic
      occlusion at early stage in rats].
AB  - OBJECTIVE: To study the intercellular communication of alveolar bone during
      traumatic occlusion at early stage in rats. METHODS: The occlusal surface of the
      upper left first molar of rat was raised by placing a stainless steel wire to
      induce occlusal trauma in the lower left first molar. After 24 hours, the
      alveolar bone tissues of the lower jaws first molars at the both sides were taken
      out under anesthesia The various 27 000 genes were identified with genome-wide
      microarray, and further were investigated with reverse transcription-polymerase
      chain reaction (RT-PCR) and Pathway analysis. RESULTS: Total 586 gene were found
      to be changed, 106 different signal pathways got involved with Pathway analysis,
      including cell adhesion molecules(CAMS), adhesions junction, gap junction, focal
      adhesion and tight junction, and the cytokines associated with bone metabolism in
      above 5 signal pathways were all down-regulated. CONCLUSION: At the early phase
      of the occlusal trauma, intercellular communication in rat's alveolar bone were
      inhibited.

PMID- 23173311
TI  - [A study on the penetration abilities of natural initial caries lesions with
      resin infiltration].
AB  - OBJECTIVE: To compare the penetration abilities of resin infiltration into
      natural initial caries lesions with those of adhesive in vitro. METHODS: Thirty
      six extracted human molars and premolars showing proximal white spot lesions were
      selected. Teeth roots were removed, and the crowns were cut across the caries
      lesions perpendicular to the surface. Corresponding lesion halves were etched for
      2 min with 15% hydrochloric acid gel and were subsequently treated with either
      adhesive or resin infiltration. Specimens were observed with confocal laser
      scanning microscopy (CLSM) in dual fluorescence mode. In confocal microscopic
      images, penetration depth (PD) and lesion depth (LD) were defined as the distance
      from the surface to the deepest point of red and green fluorescence,
      respectively. The penetration percentages (PP) were calculated. RESULTS: At the
      same level of caries, mean maximum lesion LD were comparable for both lesion
      halves (P > 0.05). But mean maximum PD and PP of the resin infiltration were
      significantly higher than those of the adhesive (P < 0.01). CONCLUSION:
      Penetration of enamel caries lesions is observed in the adhesive and the resin
      infiltration. But the resin infiltration is capable of penetrating almost
      completely into enamel parts of natural caries lesions.

PMID- 23173312
TI  - [Low intensity pulsed ultrasound irradiating combined with guided bone
      regeneration for promoting the repair effect of periodontal bone defect].
AB  - OBJECTIVE: To study the repair effect of low intensity pulsed ultrasound (LIPUS)
      irradiating combined with guided bone regeneration (GBR) on the defect of Beagle
      dog canines periodontal bone. METHODS: Four canine teeth of every beagle dog (8
      beagle dogs) were randomly distributed: Group 1 (LIPUS disposal + GBR+ autogenous
      bone graft group), group 2 (LIPUS disposal + autogenous bone graft group), group
      3 (GBR + autogenous bone graft group), blank control group. The model of
      periodontal bone defect was established in the 1/3 part of the root buccal area.
      According to the group division, autogenous bone were grafted, group 1 and group
      2 were disposed by LIPUS 20 min x d(-1). The intensity of ultrasound were 30 mW x
      cm(-2). Group 1 and group 3 were injected with Bio-Gide collagen membrane. The
      beagle dogs were executed at 6 and 8 weeks of the disposal of LIPUS and then
      Micro-CT test and analysis were conducted to periodontal bone defect area of each
      group. RESULTS: By clinical observation, there were different degrees of
      shrinkages of the area of periodontal bone defect in each group. The Micro-CT
      test analysis indicated that there was a statistical difference among the number,
      the thickness as well as the size of bone trabecula of each group (P < 0.05).
      However, there was no statistical difference (P > 0.05) in terms of bone issue
      measurement index between 6 to B weeks of each group. Group 1 had the most new
      bone. CONCLUSION: LIPUS has the potential to promote the repair of periodontal
      bone defect. Therefore the combination of LIPUS and GBR may be more conducive to
      the repair and regeneration of periodontal bone defect.

PMID- 23173313
TI  - [Effect to demineralization and remineralization of enamel surface by fluorine].
AB  - OBJECTIVE: To analyze the mechanism of fluorine by systemic analysis of
      fluorination-demineralization-remineralization experiments. METHODS: The enamel
      specimens were randomly assigned to untreated group (group A), non-fluoride group
      (group B), low-fluoride group (group C) and high-fluoride group (group D). The in
      vitro model of fluoride enamel was established in group C and D. Based on that,
      the establishment of demineralization model and remineralization experiment by pH
      cycling in group B, C and D were followed. All enamel specimens were observed by
      stereomicroscope and scanning electron microscope and compared in surface
      microhardness value. RESULTS: There was distinct difference in micro-morphologic
      appearance on fluoride enamel surface. Artificial caries of fluoride enamel
      showed a relatively complete surface, the surface microhardness after
      demineralization and remineralization in fluoride group was higher than non
      fluoride group (P < 0.05). CONCLUSION: The fluorinated enamel can enhance
      cariostatic potential and remineralization capacity of dental enamel.

PMID- 23173314
TI  - [Assessment of referral cases for root canal therapy].
AB  - OBJECTIVE: To assess referral cases for root canal therapy to provide clinical
      evidence with establishment of referral system. METHODS: A questionnaire was
      designed to collect 312 cases (355 teeth) referred to Department of Conservative
      Dentistry and Endodontics, West China School of Stomatology, Sichuan University
      for root canal therapy from April to June in 2011. The questionnaire consisted of
      questions such as age, gender, occupation, general disease and medical histories
      of patients, sources. Difficulty of treatment before therapy and reasons for
      referral were evaluated. RESULTS: In 355 referral teeth, the most were mandibular
      first molars (17%), the greatest percentage of reasons were calcified root canals
      (30%), the second was root canal retreatment (24%). 72% of teeth belong to the
      complicated difficulty (Class III), while 7% were listed as the uncomplicated
      difficulty (Class I). No significantly difference from different sources was
      found (P = 0.9). CONCLUSION: Establishment of referral system needs cooperation
      with every dentist. Difficulty of cases for root canal therapy before treatment
      should be first evaluated to treat or to refer. Referral cases for root canal
      therapy should be treated by endodontist of corresponding level according to the
      difficulty.

PMID- 23173315
TI  - [Study of the pragmatic of saliva test cassette to detect the Helicobacter pylori
      in oral cavity].
AB  - OBJECTIVE: To study the link of Helicobacter pylori salive test cassette (HPS)
      and 13C-urea breath test (13C-UBT) on detecting Helicobacter pylori infection of
      stomach, and the sensitivity as well as specificity should be determined.
      METHODS: A screening trial of 13C-UBT and HPS tests was carried out 130 patients
      included 106 positive and 24 negative results of 13C-UBT. As gold standards of
      13C-UBT, a comparison study with HPS was evaluated using Bayes formula. RESULTS:
      The sensitivity, specificity, accuracy, positive and negative predictive value of
      HPS was 68.87%, 58.33%, 66.92%, 87.95%, 29.79% respectively. The coincidence was
      66.92%. CONCLUSION: There is a correlation between results of 13C-UBT and HPS.
      Combination of 13C-UBT and HPS may compensate the blind zone of 13C-UBT in
      detecting oral Helicobacter pylori infection. 13C-UBT could not be used as a gold
      standard to judge the validation of HPS in detecting Helicobacter pylori oral
      infection. The methods can be used at the same time in clinic.

PMID- 23173316
TI  - [Quality assessment on reports of randomized controlled trials of oral and
      maxillofacial surgery in China].
AB  - OBJECTIVE: To evaluate the report quality of randomized controlled trials (RCT)
      of oral and maxillofacial surgery in China during 2000-2009. METHODS: A
      comprehensive electronic search was carried out through Chinese Biomedical
      Literature Database (CBM), VIP Database for Chinese Technical Periodicals (VIP)
      and China National Knowledge Infrastructure (CNKI), and 19 kinds of journals of
      stomatology in China were also hand-searched. We identified RCT published between
      2000 and 2009, and classified into oral and maxillofacial surgery and labeled
      "random" and assessed the quality of these reports using the consolidated
      standards of reporting trials (CONSORT) statement. RESULTS: 53 RCT articles were
      included. Reporting quality of the 53 articles was not high and the CONSORT score
      was 8.2 +/- 2.5. CONCLUSION: The reporting quality of RCT of oral and
      maxillofacial surgery in China is poor. The CONSORT statement should be used to
      standardize the reporting of RCT.

PMID- 23173317
TI  - [Effect of Nd: YAG laser on the bond strength of 3 resin cements to dentin].
AB  - OBJECTIVE: To observe the microscopic characteristic of the bonding interface
      between resin cement and dentin before and after using Nd: YAG laser, and
      evaluate the effects of the Nd: YAG laser on the shear bond strength of 3 resin
      cements to dentin. METHODS: 30 human premolars were cut into nearly equal halves,
      prepared to expose the dentin and randomly divided into two groups: Laser group
      and control group. The teeth in the laser group were processed with pulse Nd: YAG
      laser (0.8 W, 10 Hz) for 25 s, and then the teeth were bonded using 3 resin
      cements (RelyX ARC, Panavia F and RelyX Unicem) to dentin. All teeth in the
      control group were directly filled with 3 cements. The shear bond strength of
      specimens was measured. Each fractured specimen was examined under dental
      microscope. And 6 new human premolars were prepared into standard bonding
      specimens. After 3 teeth processed with pulse Nd: YAG laser, all teeth were
      bonded using 3 resin cements. To observe the microscopic characteristics of the
      bonding interface between resin cements and dentin. RESULTS: Nd: YAG laser on
      dentin surface could increase bond strength of Panavia F and RelyX Unicem (P <
      0.05). And the laser could decrease bond strength of RelyX ARC (P < 0.05). Most
      of the fractured adhesive dentin surfaces were adhesive failure modes. Scanning
      electron microscope (SEM) observation demonstrated that Nd: YAG laser irradiation
      on dentin surface could decrease the hybrid layer and resin tags between the
      resin cements (RelyX ARC and Panavia F) and dentin. The interface between RelyX
      Unicem and dentin showed no obvious change, and resin tags were not observed.
      CONCLUSION: Nd: YAG laser on dentin surface can increase bond strength of Panavia
      F and RelyX Unicem. Therefore, they can be used together in clinic.

PMID- 23173318
TI  - [Incidence of human herpes virus 1-4 type in saliva of 245 human immunodeficiency
      virus-infected patients].
AB  - OBJECTIVE: To determine the incidence of human herpes virus (HHV) 1-4 type
      including herpes simplex virus type-1 (HSV-1), herpes simplex virus type-2 (HSV
      2), varicella-zoster virus (VZV), Epstein-Barr virus(EBV) in the saliva of human
      immunodeficiency virus (HIV) -infected patients. METHODS: The incidence of
      salivary HSV-1, HSV-2, VZV and EBV from 245 HIV-seropositive individuals and
      control group was used to investigate by polymerase chain reaction(PCR) or nested
      PCR. The data was analyzed by SPSS 18.0 statistical software. RESULTS: In the 245
      HIV-seropositive individuals, the detection rates of HSV-1, HSV-2, VZV, EBV were
      29.0%, 3.3%, 4.1%, 82.0%. In the control group, the detection rates of HSV-1, HSV
      2, VZV, EBV were 13.3%, 0, 0, 36.7%. Four HHVs were significantly more prevalent
      in the salivas of HIV-seropositive persons than those in the control group (P <
      0.01). The detection rates of HSV-1, HSV-2, VZV and EBV DNA were no difference
      between the HIV-positive group with highly active antiretroviral therapy (HAART)
      and HIV-positive group without HAART (P > 0.05). CONCLUSION: There is a high
      prevalence of HHV infection in HIV-infected people in Yunnan. The most common
      virus are EBV, followed by HSV-1, but VZV and HSV-2 are rarely detected. HHV co
      infection is also observed.

PMID- 23173319
TI  - [Protein-protein interaction network of receptor activator of nuclear factor
      kappaB ligand and macrophage colony-stimulating factor induced differentiation of
      osteoclasts].
AB  - OBJECTIVE: To systemically investigate receptor activator of nuclear factor
      kappaB ligand (RANKL) and macrophage colony-stimulating factor (M-CSF) induced
      differentiation of osteoclasts. METHODS: Mouse protein-protein interaction(PPI)
      database NIA and published microarray dataset GES16749 were used to construct and
      analyze PPI network of RANKL and M-CSF induced mouse monocyte RAW264.7. RESULTS:
      In the PPI network, transforming growth factor beta receptor 1 (TGFBR1), Rous
      sarcoma oncogene (SRC), myelocytomatosis oncogene(MYC) and integrin beta 3
      (ITGB3) were able to interact with more proteins and they were the key nodes in
      the signaling transduction. CONCLUSION: TGFBR1, SRC, MYC and ITGB3 might be the
      key points of RANKL and M-CSF induced differentiation of osteoclasts.

PMID- 23173320
TI  - [Effect of different techniques in root canal preparation on coronal microleakage
      of endodontically treated teeth].
AB  - OBJECTIVE: To compare the effect of three techniques in root canal preparation on
      coronal microleakage of endodontically treated teeth. METHODS: Forty-eight human
      single-rooted teeth were divided into 4 groups randomly and subjected to
      different techniques on removal of smear layer. Group A, the control group,
      irrigation with hydrogen peroxide (H2O2) and normal saline (NS); group B, smear
      cleared with 5.25% sodium hypochlorite (NaClO) and ethylenediamine tetraacetis
      (EDTA) gel; group C, irrigation with Odontoson-M ultrasonics; group D, smear
      layer removed with Nd: YAG laser irradiation. Two specimens of every group were
      split longitudinally into equal segments and canal walls at coronal portion were
      examined under scanning electron microscope (SEM). Then ten teeth of every group
      were filled with warm vertical condensation by Obtura II thermoplasticized gutta
      perch injection technique and sealed with zinc oxide eugenol (ZOE). The teeth
      were immersed in 20 g x L(-1) methylene blue for 7 days, then were demineralized,
      dehydrated and cleared. Linear dye penetration was determined under a
      steremicroscope. The data were statistically analyzed. RESULTS: In group A, there
      were smear layer and debris remained and dentinal tubules were covered. In group
      B and group C, the smear layer of root canals were removed and dentinal tubules
      were open. In group D, the root canal dentinal tubules were sealed or semi-sealed
      and the smear layer were melted and ablated. The mean length of coronal
      microleakage for group A, B, C, D were (2.15 +/- 0.38), (1.75 +/- 0.28), (2.04 +/
      0.40), (1.73 +/- 0.36) mm. The analysis showed that the linear in group A was
      longer than that in group B and group D clearly (P < 0.05). CONCLUSION: The
      coronal microleakage following root canal treatment could be reduced by removing
      smear layer with different techniques in root canal preparation.

PMID- 23173321
TI  - [Study on synthesis on a novel nano-antibacterial inorganic filler and its
      antibacterial property].
AB  - OBJECTIVE: To synthesize a novel nano-antibacterial inorganic filler and provide
      a new way to give dental composite resin antibacterial property. METHODS:
      Quaternary ammonium iodide N,N,N-trimethyl-3-(trimethoxysilyl) propan-1-aminium
      iodide were organically synthesized firstly and then the N,N,N-trimethyl-3
      (trimethoxysilyl) propan-1-aminium iodide was grafted to the nano-silica particle
      to synthesize the antihacterial inorganic fillers nano-silica particle grafted
      with quaternary ammonium salt. All the products were analyzed and identified by
      infrared spectrum analysis. Then Streptococcus mutans were chosen as experimental
      object to analysis the antibacterial property of nanoantibacterial inorganic
      filler. RESULTS: Quaternary ammonium salt was grafted to the surface of nano
      silica particles successfully by infrared spectrum analysis. Compared with the
      control group, the nano-silica particle grafted with quaternary ammonium salt had
      a strong bactericidal effect on Streptococcus mutons (P < 0.01). CONCLUSION: The
      nano-silica particle grafted with quaternary ammonium salt has a strong
      antibacterial property and could be used to improve dental composite resin
      antibacterial property.

PMID- 23173322
TI  - [The effect of bleaching on fracture resistance in human dentin].
AB  - OBJECTIVE: To study the effect of bleaching on the mechanical properties of human
      dentin. METHODS: The finite element method (FEM) based the cohesive zone model
      had been employed to study the fracture resistance of human dentin. There types
      of dentin were considered, i.e. original dentin, dentin after direct-bleaching
      and indirect-bleaching. RESULTS: The bleaching treatments had large impact on the
      crack growth resistance of human dentin. The initiation toughness (1.48 MPa x
      square root of m), growth toughness (3.90 MPa x square root of m x mm(-1)) and
      plateau toughness (3.25 MPa x square root of m) of human dentin were reduced to
      1.29 MPa x square root of m, 3.45 MPa x square root of m x mm(-1) and 2.71 MPa x
      square root of m respectively after indirect-bleaching. The worst case was the
      direct-bleaching which causes significant reductions in the growth toughness
      (0.14 MPa x square root of m x mm(-1)) and plateau toughness (1.63 MPa x square
      root of m) respectively, while the initiation toughness remained the same as that
      after indirect-bleaching. CONCLUSION: The cohesive zone modeling is an effective
      tool in characterizing the fracture behavior of human dentin. Bleaching
      treatments reduce the crack growth resistance of human dentin and increase the
      risk of fracture of teeth.

PMID- 23173323
TI  - [The influence of methacryloxy propyl trimethoxyl silane on shear bond strength
      of three kinds metal and Filtek resin].
AB  - OBJECTIVE: To study the influence of three different metal alloy surfaces treated
      with primer methacryloxy propyl trimethoxyl silane (gamma-MPS) coupling agent on
      the bond strength of Filtek Z350 resin. METHODS: Total 36 specimens of nickel
      chromium(Ni-Cr) alloy, pure titanium(Ti) and aurum-palladium(Au-Pd) alloy, each
      of 12 pieces produced by lost wax casting method, were divided into 6 groups.
      After treated with gamma-MPS on the bonding surface, experimental group samples
      were adhered to Filtek Z350 resin, then compared with the surface without gamma
      MPS treatment. The tensile and shear strength of each group tested and the
      fracture sections were observed with scanning electron microscope (SEM). RESULTS:
      Comparing the Ni-Cr alloy and pure Ti experimental group with them in control
      group, the shearing strength of the experimental group was higher, and the
      differences were significant (P < 0.001). The shearing strength of the
      experimental group and control group of Au-Pd alloy were not significant (P >
      0.05). Comparing the experimental groups, the shearing strength of pure Ti was
      higher than Ni-Cr alloy, both were higher than Au-Pd alloy (P < 0.01). These
      entire specimens were adhesive fracture. Comparing with the control group, Ni-Cr
      alloy and pure Ti experimental group showed more resin juts in the fracture
      surface, while the Au-Pd alloy in experimental group showed less resin juts.
      CONCLUSION: gamma-MPS can enhance the adhesion between metal and resin, but it is
      also related to the metal composition. gamma-MPS can significantly increase the
      bond strength of resin and Ti or Ni-Cr alloy, but not the case of Au-Pd alloy and
      resin.

PMID- 23173324
TI  - [Research on flora on tongue dorsum of patients with atrophic glossitis and
      correlated factors].
AB  - OBJECTIVE: To examine the flora samples from the tongue dorsum of the atrophic
      glossitis group and to discuss the relationship so as to provide a thinking
      pattern for therapy and a clue for deeper research. METHODS: To collect personal
      information on 60 cases of atrophic glossitis and 40 cases of volunteers as
      control. The main items include general status, oral examination, salivary flow
      rate, pH value and bacteria test. All data were analyzed statistically. RESULTS:
      1) Among the 60 cases, 75.00% were female patients. Glosso-pain, dry mouth and
      taste loss were the most common symptoms. 2) In regard to the pathogenic factors,
      the systematic diseases were often visible, i.e. gastritis, coronary disease and
      anemia. 3) Oral hygiene of the patients was worse than that of the control group,
      the saliva flow rate and pH value were lower than that of the control. 4)The
      statistic analysis showed that the quantity of some bacteria of tongue dorsum and
      their detectable rate were different between the glossitis group and the control
      one, between the patients with atrophic glossitis who also suffered from
      different systematic diseases and the control group, and between the complete
      type and the partial type. These bacteria included Streptococcus sanguis,
      Stomatococcus, Staphylococcus aureus, Saccharomyces, etc. CONCLUSION: Atrophic
      glossitis is the consequence co-affected by host, circumstances of oral cavity
      and bacteria. The tangible relationship between atrophic glossitis and micro
      ecological changes on glossal dorsum has not been confirmed yet, however, flora
      change on dorsum may have relations with occurrence, and development of the
      disease.

PMID- 23173325
TI  - [Influence of novel porous calcium phosphate cement on biological behavior of
      bone marrow mesenchymal stem cells].
AB  - OBJECTIVE: To investigate the effect of novel porous calcium phosphate cement
      (CPC) scaffoldings on attachment, proliferation and differentiation of bone
      marrow mesenchymal stem cells (BMSCs). METHODS: BMSCs of Beagle dogs were
      implanted and cultured with CPC scaffoldings in vitro, tricalcium phosphate (TCP)
      and poly (lactide-coglycolide) (PLGA) scaffoldings as controls. The attachment,
      proliferation and differentiation of BMSCs were detected through morphological
      characters, growth curve and the semi-quantitative detection of alkaline
      phosphatase (ALP) and osteocalcin (OC) activity. RESULTS: Cell morphology and
      growth curve illustrated that BMSCs attached to and grown better on the surface
      of novel porous CPC scaffoldings than that of PLGA group (P < 0.05). Semi
      quantitative analysis of ALP showed that ALP expression level in BMSCs on the CPC
      and TCP group were significantly higher than that of the PLGA group (P < 0.05),
      the CPC group was slightly higher than the TCP group, but no significant
      difference was found between the two groups (P > 0.05). The staining and semi
      quantitative analysis results of OC demonstrated that calcium deposition of the
      PLGA group was significantly less than the CPC and TCP group on both observation
      point (P < 0.05), but no significant difference between the CPC and TCP group (P
      > 0.05). CONCLUSION: The novel porous CPC material used in this study has good
      biocompatibility similar to TCP but much better than PLGA which is favorable of
      BMSCs adhesion, proliferation and osteogenic differentiation. The novel porous
      CPC material is a suitable scaffolding for BMSCs to fabricate tissue-engineered
      bone in vitro.

PMID- 23173326
TI  - [Pilot study of the effect of green tea extractive epigallocatechin-3-gallate on
      degradation of collagen in dental erosion].
AB  - OBJECTIVE: To observe the effect of green tea extractive epigallocatechin-3
      gallate (EGCG) on degradation of collagen in dental erosion. METHODS: Sixty-four
      volunteers with dental erosion were randomly divided into two groups. The custom
      fitted trays were made from the heat curable braces and were injected with
      carboxymethyl cellulose sodium (CMC) hydrogel in one group (control group) or CMC
      hydrogel with EGCG added in another (experimental group). These trays were used
      during sleep and removed from oral cavity in the next morning. The content of
      carboxy-terminal telopeptide of type I collagen (ICTP) were determined by
      radioimmunoassay kit at 1 d before the experiment, and 1, 2, 3, 4 weeks after the
      experiment. RESULTS: Both the types and time showed significant effects on ICTP.
      The incubation in EGCG resulted in relatively rapid and significant (P < 0.05)
      decrease in the expression level of ICTP compared with the control group.
      CONCLUSION: EGCG can inhibit collagen degradation and improve the antierosive
      effect of dentine.

PMID- 23173327
TI  - [Repair of root fracture in maxillary second premolar with MTA: a case report].
AB  - MTA is rarely applied in the repair of root fractured section. A case of
      maxillary second premolar which fractured ten years ago had been connected with
      MTA in this article and the cone beam CT was used to evaluate the treatment
      effect.

PMID- 23173328
TI  - [Langerhans cell histiocytosis: a case report].
AB  - A case of Langerhans cell histiocytosis of the mandible was reported. A 34-year
      old woman presented with pain for one year on the gingival of the low left jaw,
      and together with pyorrhea in the past 2 months. The histopathology and
      immunohistochemical examination confirmed the diagnosis of Langerhans cell
      histiocytosis.

PMID- 23173329
TI  - [Modern toxicology of magnetic nanomaterials].
AB  - Current advances in nanobiotechnology have led to the development of new field of
      nanomedicine, which includes many applications of nano(bio)materials for both
      diagnostic and therapeutic purposes (theranostics). Major expectations and
      challenges are on bioengineered magnetic nanoparticles when their come to
      delivering drug compounds, especially to targeting anticancer drugs to specific
      molecular endpoints in cancer therapy. The unique physicochemical properties of
      these nanoparticles offer great promise in modern cancer nanomedicine to provide
      new technological breakthroughs, such as guided drug and gene delivery, magnetic
      hyperthermia cancer therapy, tissue engineering, cancer cell tracking and
      molecular magnetic resonance imaging. Along with the expanding interest in bio
      engineered magnetic nanoproducts their potential toxicity has become one of the
      major concerns. To date, a number of recent scientific evidences suggest that
      certain properties of magnetic nanoparticles (e.g., enhanced reactive area,
      ability to cross cell membranes, resistance to biodegradation) may amplify their
      cytotoxic potential relative to bulk non-nanoscale counterparts. In other words,
      safety assessment developed for ordinary magnetic materials may be of limited use
      in determining the health and environmental risks of the novel bio-engineered
      magnetic nanoproducts. In the present paper we discuss the main directions of
      research conducted to assess the toxicity of magnetic nanocompounds in
      experimental in vitro and in vivo models, pointing to the key issues concerning
      the toxicological analysis of magnetic nanomaterials. In addition new research
      directions of nanotoxicological studies elucidating the importance of developing
      alternative methods for testing magnetic nano(bio)products are also presented.

PMID- 23173330
TI  - [Fish and seafood as a source of human exposure to methylmercury].
AB  - Fish and seafood are recommended diet constituents providing high quality
      protein, vitamins, minerals and omega-3 fatty acids, mainly eicosapentaenoic acid
      (EPA) and docosahexaenoic acid (DHA). However, these foodstuffs can also be the
      major source ofmethylmercury intake in humans. In general, more than 90% of the
      mercury in fish is found as methylmercury, but contents of methylmercury can vary
      considerably between species. Predatory species that are at the top of the food
      chain and live a long time, may accumulate higher levels of methylmercury. This
      paper contains information about sources of human exposure to organic compounds
      of mercury, toxicity, metabolism and transformation of mercury in the
      environment. Assessment of methylmercury by international risk assessment bodies
      such as the Joint FAO/WHO Expert Committee on Food Additives (JECFA) and U.S.
      National Research Council (NRC) were presented. Climate changes and their
      influence on the mercury cycle in the environment especially mercury methylation
      and concentrations of methylmercury in marine species were also presented.
      Consumer advice prepared by European Commission and Member States as regards
      consumption of predatory fishes such as swordfish, tuna, shark, marlin and pike,
      taking into account the most vulnerable groups of population e.g. women planning
      pregnancy, pregnant or breastfeeding women and children were presented. Mercury
      and methylmercury contamination of fishes and seafood on the basis of the
      literature references as well as intake of mercury with fish and fish products in
      Poland and other European country were discussed. The role of selenium as a
      factor which counteracts methylmercury toxicity and protects against some
      neurological effects of methylmercury exposure in humans, as well as information
      on potential etiological factors connected with autism disorder were also
      described. Attention has also been drawn to increasing number of notifications to
      Rapid Alert System for Food and Feed (RASFF) concerning the contamination of fish
      and fish products with total mercury. European and national regulations
      concerning maximum permissible levels of mercury in food were also presented.
      Possibility of selection of different fish and seafood species, taking into
      account low methylmercury contamination and high contents of omega-3 fatty acids
      e.g. sardine, mackerel, anchovy, salmon, periwinkle, have been discussed.

PMID- 23173331
TI  - [Evaluation of the possibilities to increase the content of conjugated linoleic
      acid (CLA) in meat and meat product].
AB  - The paper characterizes pro-health properties of conjugated linoleic acid (CLA)
      and assesses the possibility of increasing their content in pork and pork meat
      products. Studies conducted on animals indicate antitumor, antiatherosclerotic
      and antiinflammatory effect ofCLA, also find impact on reducing body fat and
      increasing muscle growth. However, the number of observations concerning human
      populations is insufficient to fully evaluate the relationship between CLA intake
      and reducing the risk of lifestyle diseases. Therefore, it is necessary to
      conduct further research. Literature data indicate that the use in pigs feed
      suplementation with CLA preparations, can increase the content of these compounds
      in the meat and also show, that isomer cis-9, trans-11 is accumulated at
      significantly higher level. However, these changes were accompanied by increased
      the share of saturated fatty acids at the expense of monounsaturated which is
      unfavorable for human health. A better way to increase the CLA content in pork
      meat appears to be the addition of CLA preparation during the production process,
      because it does not affect the level of saturated fats. Pork and pork meat
      products enriched in CLA are characterized by low susceptibility to oxidation,
      which may result from the coupling of double bonds, antioxidantive properties of
      conjugated linoleic acid and the increased content of saturated fatty acids. The
      issue of beneficial effects on human health of pork and pork products with a
      higher content of CLA, requires further studies conducted on humans. Only then
      these products can be classified as a functional foods.

PMID- 23173332
TI  - Determinants of self-rated health of Warsaw inhabitants.
AB  - BACKGROUND: Self-rated health is a one-point measure commonly used for
      recognising subjectively perceived health and covering a wide range of
      individual's health aspects. OBJECTIVE: The aim of our study was to examine the
      extent to which self-rated health reflects the differences due to demographic
      characteristics, physical, psychical and social well-being, health disorders,
      occurrence of chronic disease and negative life events in Polish social and
      cultural conditions. MATERIAL AND METHOD: Data were collected by non-addressed
      questionnaire methods from 402 Warsaw inhabitants. The questionnaire contained
      the questions concerning self-rated health, physical, psychical and social well
      being, the use of health care services, occurrence of chronic disease and contact
      with negative life events. RESULTS: The analysis showed that worse self-rated
      health increased exponentially with age and less sharply with lower level of
      education. Pensioners were more likely to assess their own health worse then
      employed or students. Such difference was not found for unemployed. Compared to
      married, the self-rated health of divorced or widowed respondents was lower.
      Gender does not differentiate self-rated health. In regard to well-being, self
      rated health linearly decreased for physical well-being, for social and,
      especially, for psychical well-being the differences were significant, but more
      complicated. Hospitalisation, especially repeated, strongly determined worse self
      rated health. In contrast, relationship between self-rated health and sickness
      absence or frequency of contact with physician were lower. Chronic diseases
      substantially increased the risk of poorer self-rated health, and their co
      morbidity increased the risk exponentially. The patients with cancer were the
      group, in which the risk several times exceeded that reported for the patients of
      other diseases. Regarding negative life events, only experience with violence and
      financial difficulties were resulted in worse self-rated health. CONCLUSIONS: Our
      findings confirmed the usefulness of self-rated health for public health
      research.

PMID- 23173334
TI  - [Assessment of the effect of selected mixture of food additives on the protein
      metabolism--model studies].
AB  - BACKGROUND: Contemporarily, food production without food additives is very rare.
      Increasingly often, however, scientific works report on adverse effects of
      specified, single food additives on the body. Data is, in turn, lacking on the
      synergistic effect of a mixture of different food additives on body functions and
      its main metabolic pathways. OBJECTIVE: The objective of this study, an animal
      model, was to evaluate if and in what way the compound of chosen and most
      frequently used and consumed food additives, along with the change of diet
      composition to processed, purified, influence the selected markers of protein
      metabolism. MATERIAL AND METHODS: The animals were divided into four groups,
      which were fed with compound of feed pellets: group I and II with basic compound,
      group III and IV with modified compound in which part of the full grain was
      replaced by isocalorie wheat flour type 500 and saccharose. Animals from groups I
      and III received tap water, which was standing for some time, to drink. Animals
      from groups II and IV received solution of chosen additives to food and next they
      were given water to drink. The amount of given food additives was evaluated by
      taking into consideration their consumption by people recalculated to 1 kg of
      their body mass. The experiment spanned for 7 weeks. RESULTS: It was ascertained
      that the applied additives caused significant changes in total protein
      concentration and its fractions: albumin, alpha1-globulin, alpha2-globulin, beta
      globulin and gamma-globulin in the blood serum of the animals under research,
      which can indicate and contribute to disclosure of creation of undesirable food
      reaction, especially when recommended levels of consumption of those additives
      are being exceeded. The organism response to the applied additives and
      accompanying it change of diet was essentially connected to sex of the animals.
      Undesirable character of changes taking place under the influence of applied
      additives, was observed both in animals fed with basic feed and modified feed
      with various intensity according to the parameter under research. CONCLUSIONS:
      The analysis of the results achieved enabled concluding that the applied mixture
      of food additives caused significant changes in the concentration of total
      protein and its fractions: albumins, alphal-, alpha2-, beta- and gamma-globulins
      in blood serum of the investigated animals. These changes may indicate but also
      may contribute to the development or manifestation of undesirable nutritional
      responses, especially when recommended dietary allowances are exceeded. The
      body's response to the applied additives and concomitant modification of diet
      composition was significantly correlated with sex of the animals. The unfavorable
      character of changes following the administration of additives was observed in
      both the animals on the basal diet and these fed the modified feed mixture, yet
      with a different intensity that was found to depend not on the feeding group but
      on the parameter examined.

PMID- 23173333
TI  - Assessment of atherogenicity of students daily diets of Wroclaw Medical
      University.
AB  - BACKGROUND: Results of the research indicate that excessive consumption of
      products that are a rich source of the saturated fatty acids (SFA) and
      cholesterol, and disturbed balance in the monounsaturated fatty acids (MUFA) and
      polyunsaturated fatty acids (PUFA) intake could affect the development of
      atherosclerotic lesions since the childhood. OBJECTIVE: The aim of the study was
      to evaluate the atherogenicity of the students diets, based on the content of
      various fatty acids (FA), their relative proportions, and the content of
      cholesterol. MATERIAL AND METHODS: The study group included 127 students (female
      100, male-27) of Wroclaw Medical University. Dietary habits in the study group
      were evaluated by the method of the three-day diet record including one weekend
      day. In total 381 dietary interviews: 300 from female and 81 from male were
      analyzed. RESULTS: The percentage of energy from SFA was higher than recommended
      10%. The average percentage of energy from SFA in the diets of male and female
      was 14.3% and 15.6%. The average percentage of energy from MUFA in the diets of
      female and male was respectively 12.8% and 15.3%. The recommended average
      percentage of energy from MUFA is > or = 14% of daily energy requirements. The
      daily intake of cholesterol should be less than 300 mg/day. The average content
      of cholesterol in the diets of female was 278.7 mg/day, and male 428.1 mg/day.
      The Keys atherogenic score assessed in the diets of female was on average 49.2
      with recommended values of 30.1-35.5, and 52.3 in the diets of male at the
      recommended values of 28.4-33.8. Atherogenicity estimated by P/S ratio in both
      students groups was 0.4 at the recommended values of > or =1. The recommended
      daily percentage of energy from PUFA is 6-10%. The percentage of energy from PUFA
      in the average diet of female was 5.3%, and 6.0% in the male diets. The sum of
      EPA and DHA in the female diets was average 0.1 g/day, and the n-6/n-3 PUFA ratio
      was 5.8:1 (recommended 4:1). The sum of EPA and DHA in the male diets was 0.2
      g/day, and the n-6/n-3 PUFA ratio was 6.1:1. CONCLUSIONS: It was shown that
      studied students diets may promote the development of atherosclerotic lesions.

PMID- 23173335
TI  - [Assesment of energy and basic components intake in selected group of the
      breastfeeding women].
AB  - BACKGROUND: Breastfeeding is considered the most beneficial, natural nutrition
      for babies. Qualitative and quantitative composition of breast milk is ideal for
      implementing all the nutritional needs of infants up to 6 months of age, assuming
      that the nursing mother's diet is correct. OBJECTIVE: The aim of the study was to
      evaluate the intake of energy, proteins, fat, carbohydrates and cholesterol in
      the group of 100 breastfeeding women, aged 19 to 38 years, from Masovian
      province. MATERIAL AND METHOD: The survey was conducted from September 2010 to
      March 2011. The results were obtained using a questionnaire survey and the 3-day
      dietary records method. RESULTS: Energy intake was compatible with the norms in
      9% of women. As many as 91% of respondents characterized too high energy intake.
      Protein intake according to the norm was recorded in 64% of women, fat in 45% of
      respondents. Recommendations intake of polyunsaturated fatty acids was observed
      in 61% of group, saturated acids in 15% of women, carbohydrate in case of 36% of
      respondents. Cholesterol intake was too high at 45% of women. There was a
      statistically significant effect of education on intake of total fat and
      saturated fatty acids and polyunsaturated fats, sucrose and energy value. Women
      with higher education consumed 12% to 20% more of these nutrients compared to
      women with secondary education. CONCLUSIONS: There is need for further education
      of women during lactation on the importance of their properly balanced diet, as
      assessed food rations of lactating women have shown a lot of irregularities.

PMID- 23173336
TI  - [Evaluation of the nutrition model in students of university in Rzeszow].
AB  - BACKGROUND: Adequate nutrition is an essential factor conditioning physical and
      mental development of man, and poor nutrition can cause deterioration of health
      and occurrence of diseases related to diet. The fashion for slim body promoted in
      the media contributes to the youth's activities aiming to shape their bodies and,
      in particular, studying persons run the risk of nutritional deficiencies, which
      is also connected with irregular time of classes. OBJECTIVE: The aim of the study
      was to evaluate the diet of 200 students (161 women and 39 men) in the second
      year of Food Technology and Human Nutrition at the University of Rzeszow and to
      evaluate the extent to which nutritional standards for energy and essential
      nutrients in the daily food rations are kept. MATERIAL AND METHODS: The tests
      were carried out in the years 2010-2011. Intake assessment was made by the method
      of current listing of products and beverages consumed in the successive three
      days. Portion size was estimated by using the "Album of photographs of products
      and dishes." Using the "Tables of the nutritional value of food products and
      dishes," there was calculated the energy value, content of essential nutrients
      and cholesterol. The obtained results of the energy value were compared with the
      "Human Nutrition Standards" for women and men aged 19-30 years of moderate
      physical activity, and the nutritional value of analyzed diets was compared with
      standards of recommended dietary allowance (RDA). RESULTS: Diets of students
      (women and men) were significantly different (p = 0.01) in terms of energy
      content and nutritional value. Food rations for women and men were characterized
      by low energy value not corresponding to the recommendations of the Human
      Nutrition Standards. The energy value of diets of tested women students was
      1568,56 kcal/day, while of men students 2283,22 kcal/day. Protein supply in daily
      food rations for women was 56,73 g and corresponded to the recommendations of the
      standards, while in the group of men it exceeded the standard at the recommended
      intake level and amounted to 89,32 g. Fat intake was consistent with the
      recommendations of the standards for both women and men and it was 59,67 g and
      89,09 g respectively. The level of carbohydrate intake exceeded the standards at
      the level of recommended intake in daily food rations of women and men (213,14 g
      and 286,04 g). Average intake of cholesterol was 239,08 mg and 394,92 mg
      respectively. These values are close to the limit set by American Heart
      Association. CONCLUSIONS: Daily food rations of students of the University of
      Rzeszow under the study were characterized by low energy value. In the analyzed
      daily food rations of women was found the protein content at the level of
      recommended intake whereas in the group of men these values exceeded the
      recommendations of standards. In both groups the fat intake was at the level of
      recommended intake and the carbohydrate content was at a higher level than the
      recommendations of standards.

PMID- 23173337
TI  - [Food patterns of youth from gymnasium and lyceum].
AB  - BACKGROUND: Children and adolescents are the most vulnerable for the impact of
      improper nutrition. The mode of nutrition is one of the factor influencing the
      proper development and growth of young organism and the maintenance of good
      health until advanced old age. OBJECTIVE: The food pattern of youth from selected
      Warsaw gymnasium and lyceum was evaluated. MATERIAL AND METHODS: Author's
      questionnaire, 24h interview and Block questionnaire were used. RESULTS:
      Irregularity of main meals intake, between meals consumption (sweets and salts
      snacks mainly and fruits also) as well as tea, fruit juices and mineral water
      drinking were observed in youth of both schools. More than half of them took cola
      drinks every day and half of youth drank coffee permanently. The daily ratios of
      both groups were short in fibre and too rich in fats. Fats intake was more proper
      among gymnasialists. Youth's daily ration in both types of school were poor in
      vitamin C, D, E as well as calcium, potassium and magnesium. They were too rich
      in vitamin A in some cases (7%) over UL. Also, vitamin B2, B6 i B12 and sodium,
      copper, iron (boys) exceeded recommendations. CONCLUSIONS: No statistically
      significant differences in food pattern between gymnasium and lyceum youth were
      observed however in girls the one was more proper. In order to optimise the mode
      of nutrition the monitoring established on the constant base and education for
      parents, teachers and adolescents are needed.

PMID- 23173338
TI  - [Assessment of intake of minerals with daily diets by children aged 10-12 years
      from Malopolska region].
AB  - BACKGROUND: Adolescence is a time of rapid growth and development of the
      organism. During intense growth and maturation changes taking place in the body,
      it cost higher demand for energy and nutrients including minerals. OBJECTIVE: The
      aim of this study was to assess the intake of sodium, potassium, calcium,
      phosphorus, magnesium, iron, zinc, copper and manganese with daily diets by
      children aged 10-12 years. MATERIALS AND METHODS: Assessment of intake of mineral
      compounds from daily diets was conduced with using 24 hours recall. Data were
      collected in spring and autumn of 2006 in randomly selected primary schools in
      Krakow and Skawina. Average intake of minerals (Na, K, Ca, P, Mg, Fe, Zn, Cu, Mn)
      with daily diets by respondents and the meeting of requirements was estimated
      with using the computer softwere Diet 2. RESULTS: In almost all cases intake of
      minerals with daily diets did not meet requirements. Daily dies of children did
      not met requirements for major minerals i.e. calcium and magnese, and for trace
      minerals copper, zinc, iron. Insufficient intake of calcium, while fully covering
      the demand for phosphorus, resulted in improper ratio these minerals in the diet
      (0.62 at the recommended, of 1). Intake of manganese and potassium fully covered
      demand, while the sodium and salt were taken in excess. CONCLUSIONS: To low
      intake of minerals compounds by children may increase the risk of development of
      diet non-communicable diseases.

PMID- 23173339
TI  - [Influence of selected factors on fortified food intake by children].
AB  - BACKGROUND: The range of food products fortified with vitamins and minerals in
      Poland is growing rapidly in the last years. Also the consumption of such food
      and dietary supplements is increasing. Therefore there is a risk of excessive
      intake of vitamins and minerals. OBJECTIVE: The aim of the study was to analyze
      the determinants of intake of food products fortified with vitamins and minerals
      among children aged 6-12. MATERIAL AND METHODS: Data was collected by a
      questionnaire specially developed and a FFQ method including vitamins and/or
      minerals in fortified food products. There were collected data from parents of
      743 children (374 boys, 369 girls) attending primary schools, placed in four
      different districts of Poland. RESULTS: More than 70% of children consumed food
      products fortified with vitamins and/or minerals, among them 76% - every day. As
      a main reason of intake of fortified food by children, parents mentioned the
      beneficial effects on health (86.2% parents) and taste preferences (61.2%).
      However, the main reason of no consuming this kind of products, were proper
      nutrition of the children (57.4%), no influence on health (30.3%) and prohibitive
      price (24,1%). There were statistically significant relationships between intake
      of food fortified with vitamins and/or minerals and children's age (75.8% of age
      6-9 years vs. 58.1% of age 10-12 years), health condition (71.6% of children with
      good and very good health status -assessed by parents - vs. 55.6% with average
      and poor health status), the number of meals eaten during the day (75.6% eating 4
      meals/day vs. 67.8% - 5 and more meals vs. 52.3% - 3 meals), regular breakfast
      eating (71.8% eating vs. 50.0% non consumption), brunch eating (73.3% vs. 54.0%
      respectively), afternoon snack eating (75.7% vs. 59.4%) and using of dietary
      supplements (84.6% among children who use supplements vs. 61.4% among non users).
      CONCLUSIONS: It was established that about 22% of parents were unaware that their
      children consumed food fortified with vitamins and/or minerals. Food fortified
      with vitamins and/or minerals was consumed more frequently among younger
      children, specially among those who eat more meals per day and with good and very
      good health status. Due to the fact that many children consumed both fortified
      foods and dietary supplements, there is a risk of exceeding levels consider as
      safe (UL) of some vitamins and/or minerals.

PMID- 23173340
TI  - [Assessment of mineral bottled water as a source of selected minerals among
      students].
AB  - BACKGROUND: Given the range of natural mineral waters, natural spring waters and
      table waters, and their degree of mineralization (from low to the high), it can
      be assumed that they will become increasingly important as a source of minerals
      in everyday diet. OBJECTIVE: The aim of the study was the assessment of the
      amount of bottled waters consumption as well as contained selected minerals in
      waters among female students. MATERIAL AND METHOD: Study was conducted among 18
      26 years old students from Warsaw University of Life Sciences (SGGW) and Cardinal
      Stefan Wyszynski University in Warsaw (UKSW) (50 female from each), from May to
      October 2010 year. The study was performed by using the questionnaire concerned
      habitual consumption of bottled waters. Intake of calcium, magnesium, sodium,
      potassium, silicon, chlorine and fluorine, as the major components of water
      declared on the label packaging, was also estimated. RESULTS: Almost 40% of
      respondents consumed four glasses of water a day, about 24% - 2 glasses, about
      24% - 3 glasses, 11% - 1 glass, but it was mainly low- and medium-mineralized
      water. The average daily intake of calcium, magnesium, sodium, potassium,
      chlorine and fluorine in the study population was respectively: 64.1, 26.5, 14.3,
      1.9, 5.4, and 0.1 mg per person. Intake of silicon was 14, 4 mg/person/day. Among
      minerals only calcium and magnesium intake with waters was comparatively
      significant (6% and 8% of reference values, respectively). CONCLUSIONS: Bottled
      waters were not a significant source of minerals, but they can be a valuable
      addition to daily diet. There is a need to promote the drinking of natural
      mineral waters, spring waters and table waters, especially highly-mineralized and
      low-sodium waters as a source of well-absorbed minerals.

PMID- 23173341
TI  - [Determination of the thyreostats in animal muscle tissue by matrix solid-phase
      dispersion (MSPD) and liquid chromatography-tandem mass spectrometry].
AB  - BACKGROUND: The residues ofthyreostats must not be present in the edible animal
      tissues. The proposed in the EU minimum required performance limit (MPRL) in the
      animal tissues is 10 microg/kg. This implies the decision limit (CCalpha) and
      decision capability (CCbeta) of the analytical methods used for the determination
      of these compounds lower than 10 microg/kg. OBJECTIVE: This study aimed at the
      development, basing on the literature data and own studies the analytical method
      allowing for the identification and quantification of five thyreostats: tapazole
      (TAP), thiouracil (TU), methylotiouracil (MTU), propylothiouracil (PTU) and
      phenylotiouracil (FTU)) in the bovine muscle tissue, which would meet the
      criteria set in the Commission Decision No 2002/657/EC. MATERIAL AND METHODS: The
      developed method used liquid chromatography-tandem mass spectrometry (LC-MS/MS).
      The sample was extracted and cleaned using the matrix solid-phase dispersion
      (MSPD) method. The LC was equipped with column Luna C18 Phenomenex.
      Dimetylotiouracyl was used as internal standard. The samples were fortified at
      levels: 5, 10 and 20 microg/kg. The method was validated according to the
      criteria laid down in Commission Decision No. 2002/657/EC. RESULTS: At the
      levels, mean relative recoveries was in the range 90 - 109% and repeatability (CV
      %) was less than 10%. Decision limit (CCalpha) and detection capability (CCbeta)
      calculated for all thyreostats were below the recommended minimum required
      performance limit (MRPL) - 10 microg/kg. CONCLUSIONS: The developed and validated
      LC-ESI-MS/MS method allows for the identification and quantification of five
      thyreostats in the bovine muscle tissue in the quantities below 10 microg/kg.
      Analytical procedure meets the criteria of Commission Decision No 2002/657/EC.

PMID- 23173342
TI  - [Evaluation of contamination of some types of honey with selected persistent
      organic polutants (POPs)].
AB  - BACKGROUND: Honey is a synonymous of healthy food. Its quality is associated with
      the state of the environment. Although persistent chlorinated hydrocarbons are no
      longer produced nor used, their residues are still detected in the environment.
      Some of these compounds are carcinogenic to humans. Continuous exposure of bees
      to various types of chemicals impacts also their products. Therefore, knowledge
      of the degree of contamination of honey may have important implications for human
      health. OBJECTIVE: The aim of this study was to assess the degree of honey
      contamination with POPs. MATERIAL AND METHODS: Six species of honey were
      analyzed, as well as rape inflorescences and soil coming from the villages
      Peczerzyno and Przybyslaw in Western Pomerania, Poland. The scope of
      investigation included organochlorine pesticides: alpha-HCH, beta-HCH, gamma-HCH,
      heptachlor, aldrin, dieldrin, endrin, heptachlor epoxid isomer B, p,p'-DDT, o,p'
      DDT, p,p'-DDE, p,p'-DDD, o,p'-DDD, dioxin-like non-ortho PCB congeners (PCB 77,
      PCB 81, PCB 126, PCB 169), dioxin-like mono-ortho PCB congeners (PCB 105, PCB
      114, PCB 156, PCB 157) and indicator PCB congeners (PCB 28, PCB 52, PCB 101, PCB
      118, PCB 138, PCB 153, PCB 180). Chromatographic separation was performed using
      gas chromatography (HP 6890) coupled with mass spectrometry (HP 5973). RESULTS:
      Among the analyzed organochlorine pesticides the highest concentration in honeys
      was noticed for heptachlor (3.89 ng/g mm). The content of indicator PCB congeners
      in honey ranged from below LOQ values to 0.02 ng/g w.w. The content of non- and
      mono-ortho PCB congeners in honey were relatively low, reaching a maximum 0.02
      ng/g w.w. CONCLUSIONS: The content of the analyzed organochlorine compounds in
      the material depended on the location of sampling sites, and the highest
      concentrations were found in rape inflorescences. The soil and rape
      inflorescences from Peczerzyno were the most contaminated with POPs, but it had
      no clear impact on the content of the compounds in honey. Buckwheat honey was
      significantly (p<0,05) least contaminated with POPs. The content of the examined
      POPs in honeys was low and safe for consumers health.

PMID- 23173343
TI  - [Influence of diesel fuel on the number of selected soil microorganisms group].
AB  - BACKGROUND: Among a range of xenobiotics, that are introduced into the
      environment, especially dangerous are petroleum substances. Microorganisms
      participating in their decomposition, may be a good effectiveness indicator of
      biodegradation process. OBJECTIVE: The aim of this study was to determine the
      influence of soil contamination with diesel oil for changes in number of basic
      taxonomic groups of microorganisms, including bacteria, actinomycetes and fungi.
      MATERIAL AND METHOD: The study was carried out in two soils, loamy sand and sandy
      clay, which, apart from granulometric composition also differed in organic matter
      content. Two levels of diesel contamination was used: 5% and 15% w/w of soil d.m.
      The soil samples, not contaminated with diesel oil, was left as a experience
      control objects. The number of microorganisms were evaluated by automated method
      with measuring impedance in media, using the analyzer BacTrac 4100. RESULTS: In
      the studied soils the largest group of microorganisms were bacteria,
      significantly less was fungi and actinomycetes. Based on the results of research
      it was found a significant effect on the quantitative composition of microflora
      was both contamination dose and type of soil. Diesel fuel at a concentration of
      5% stimulated the number of bacteria and fungi in sandy soil. In general,
      increase in concentration of pollutants adversely affect the microorganisms,
      especially in loamy soils. Soil contamination with diesel oil resulted in a
      reduction in the degree of microbial growth rate (55% in loamy sand and 39% in
      sandy clay), and thus have an impact on their fertility. The reduction of SR
      index was correlated with increasing dose of pollutants. CONCLUSIONS: Diesel oil
      affect the biological balance of soil and stimulates or reduces the number of
      different groups of microorganisms, depending on the amount of fuel. The presence
      of fuel decrease index of soil fertility, proportion to increase in the level of
      contamination.

PMID- 23173344
TI  - [Population aging: the challenges of success].

PMID- 23173345
TI  - [Principles for the assessment and management of polymorbid elderly patients: a
      guide for clinicians].
AB  - Providing care to multimorbid older patients is complex, not only because of the
      coexistence of multiple chronic conditions, but also because of their frequent
      intrication with psychological and social problems. This article describes a
      guide for clinicians to assess and manage multimorbid older patients. This guide
      was adapted from the work of a group of expert US geriatricians. It proposes
      seven steps: identification of the main problem; identification of patients'
      preferences; setting of goals of care; estimation of life expectancy;
      identification of relevant evidence in the literature; revision of the plan of
      care; and discussion of the options with the patient. The use of this guide is
      illustrated by a clinical case.

PMID- 23173346
TI  - [Assessment of life expectancy in older people].
AB  - Evaluation of the remaining life expectancy in elderly persons plays an important
      role in their care, most importantly when treatments are associated with severe
      side effects or when they reduce the quality of life. Prognostic scores,
      incorporating the functional status in addition to age and comorbidities, enable
      evaluation of the mortality risk during different periods of time. Despite some
      limitations, these scores are useful in establishing individualized treatment
      plans.

PMID- 23173347
TI  - [Assessment of behavior in non-psychiatric settings: use of a simple and reliable
      method].
AB  - Behavioral and psychological symptoms of dementia are the most common
      complication in hospitalized older people with dementia. This article describes
      the development of a French version of a simple and reliable scale that is easy
      to use in somatic settings to foster clear and objective communication around
      this symptomatology.

PMID- 23173348
TI  - [Teaching skills of functional assessment to medical students: why not playing
      games?].
AB  - Today, physicians take care of an aging population suffering from multiple
      chronic diseases and disabilities. Therefore, a good knowledge of functional
      assessment is required, and this topic should be addressed in the undergraduate
      medical curriculum. This article reports our experience with a seminar on
      functional assessment using an "aging game" as a pedagogic vector. This seminar
      is organized by geriatricians, occupational therapists and physical therapists.
      Medical students are exposed to situations where they experiment disabilities and
      try to elaborate compensatory strategies. Then, they reflect on a complex
      discharge project by analyzing a written clinical case. Finally, they are
      introduced to the use of validated functional assessment instruments. Evaluation
      indicated that this pedagogic approach is highly valued by students and fosters
      the acquisition of knowledge in functional assessment.

PMID- 23173349
TI  - [How to prevent functional decline: an acute care integrated model for the
      elderly].
AB  - Hospitalization in older patients is frequently associated with functional
      decline. Hospital factors and inadapted process of care are factors leading to
      this decline. Acute care units specifically developed for older patients can
      prevent functional decline. These units usually include a comprehensive geriatric
      evaluation, an interdisciplinary meeting, protocols for the treatment of
      geriatric syndromes and specific teaching for the care team. Globally, patients'
      cares are organized to preserve and improve functional performances. This article
      presents a pilot unit inspired by this model.

PMID- 23173350
TI  - [Intermediate geriatric care in Geneva: experience of ten years].
AB  - Population aging has generated an increased demand for acute healthcare services
      in persons aged over 65, who may represent up to half of all patients treated in
      intensive care units (ICU). However, the number of available ICU beds is limited.
      Intermediate care units (IntCU) require less human and technical resources, and
      may represent an interesting alternative to intensive care in the geriatric
      population. This article describes a 10-year, single centre experience at a
      geriatrics IntCU in Geneva. We observed a significant reduction in in-hospital
      mortality after the creation of the IntCU (2000-2001) compared to the 2 years
      immediately preceding its inception (1998-1999).

PMID- 23173351
TI  - [Vitamin D and chronic kidney disease: increasing role for an old vitamin].
AB  - Patients with chronic kidney disease exhibit a high mortality risk that is not
      fully explained by the classical cardiovascular risk factors. Vitamin D
      deficiency highly prevalent among CKD patients is independently associated with
      an increased mortality risk in this population. Advances in the understanding of
      vitamin D physiology dramatically changed the view on the role of this vitamin in
      kidney disease. Extra-renal actions on a variety of tissues have been identified.
      By its cardiovascular effects for instance, correction of vitamin D insufficiency
      might help to reduce the excess of mortality among patients with chronic kidney
      disease. This article summarizes the sum of knowledge on the roles of vitamin D
      in kidney disease. Recommendations on screening and substitution with vitamin D
      in this high-risk population are then proposed.

PMID- 23173352
TI  - [Believing it all . . . ].

PMID- 23173353
TI  - [Medications: evidence of counterfeit drugs].

PMID- 23173354
TI  - [Reflecting our black bile].

PMID- 23173355
TI  - [Aquila, Italy, where the seven experts were punished with prison].

PMID- 23173356
TI  - [Individual boundaries of a person].

PMID- 23173357
TI  - Sharp healthcare's risk-sharing strategy.

PMID- 23173358
TI  - Is the slowdown in healthcare spending sustainable?

PMID- 23173359
TI  - 5 ways to attract the most highly qualified travel nurses.

PMID- 23173360
TI  - Maximizing value from anesthesia services.

PMID- 23173361
TI  - Health insurance exchanges bring potential opportunities.
AB  - The introduction of the state health insurance exchanges, as provided for in the
      Affordable Care Act, has many strategic implications for healthcare providers:
      Unprecedented transparency; The "Walmart Effect", with patients playing a greater
      role as healthcare consumers; A rise in narrow networks spurred by low prices and
      narrow geographies; The potential end of the cross subsidy of Medicare and
      Medicaid by commercial plans; The possible end of not-for-profit status for
      hospitals

PMID- 23173362
TI  - Perspectives on medical malpractice self-insurance financial reporting.
AB  - Financial reporting of medical malpractice self-insurance is evolving. The
      Financial Accounting Standards Board Accounting Standards Codification Section
      954-450-25 provides guidance for accounting and financial reporting for medical
      malpractice. Discounting of medical malpractice liabilities has been reassessed
      in recent years. Malpractice litigation reform efforts continue in several
      states. Accountable care organizations could increase the frequency of medical
      malpractice claims because of patients' heightened expectations regarding quality
      of care.

PMID- 23173363
TI  - 5 strategies for building a top-performing hospital.
AB  - A hospital's strategy for attaining high performance under value-based business
      models should focus on five key objectives: Building meaningful scale and scope;
      Focusing on more integrated care delivery and management; Attaining demonstrably
      high levels of clinical quality; Differentiating from the competition through
      superior customer service; Establishing a competitive cost position.

PMID- 23173364
TI  - Are your physician-integration strategies sustainable?
AB  - Before embarking on a physician-integration strategy, hospitals and health
      systems should perform a detailed analysis of the following four critical areas
      to ensure that the strategy is competitive and sustainable: Strategic objectives;
      Financial resources; Requisite experience and functional capabilities;
      Organizational structure, culture, and commitment.

PMID- 23173365
TI  - The urge to merge.
AB  - For many stand-alone hospitals, a merger, partnership, or affiliation may be the
      only option to access scale and remain viable in the nation's emerging new
      healthcare delivery system. These organizations can consider many options for
      affiliation, including traditional options such as affiliation with regional
      academic medical centers, a merger or takeover to become the corporate member of
      a large system, and acquisition by a for-profit system. Emerging options include
      mergers for scale and access to capital, private-equity transactions, and
      arrangements involving insurance vertical integration.

PMID- 23173366
TI  - Outlook for independent community hospitals: uncertain.
AB  - Increasing financial pressures in the healthcare marketplace have made it
      imperative for many independent community hospitals to conduct assessments to
      determine the viability of continued independence. For organizations initiating
      such assessments, the decision of whether to affiliate with another organization
      is as much about when to act as it is about whether to seek a partner. Even if
      all indicators considered point to a need to consolidate, there remains one
      critical concern in identifying the best partner for a successful combination:
      whether the two organizations are culturally compatible.

PMID- 23173367
TI  - Distressed industries: lessons for U.S. health care.
AB  - Steps that healthcare organizations can take now to ensure their survival are to:
      Embrace a sense of urgency; Appreciate patients' cost concerns; Evaluate labor
      costs; Encourage strong leadership and coordination.

PMID- 23173368
TI  - 4 pitfalls to clinical integration.
AB  - Four common mistakes can easily thwart clinical integration: Assuming that EHR
      adoption is the cornerstone of successful integration; Delaying the development
      of ambulatory services that support clinical integration; Believing that
      knowledge of clinical integration initiatives will passively diffuse through the
      ranks; Attaching too much weight to Federal Trade Commission/Department of
      Justice approval of a clinical integration model.

PMID- 23173369
TI  - Applying the ABCs in provider organizations.
AB  - Activity-based costing (ABC) is an accounting technique designed to guard against
      potentially serious financial problems that can arise when an organization's
      accounting costs deviate significantly from its actual costs. In general, an ABC
      analysis considers two factors: a cost element (a directly measurable unit of
      cost, such as the cost of an item) and a cost driver (a directly measurable
      feature of the service, such as how often the item is used). ABC is best applied
      to specific service areas, orservice packages, for which consumption of resources
      is largely predictable and atomic units of services can be accurately identified.

PMID- 23173370
TI  - Equity versus adequacy of managed care contracts.
AB  - Healthcare finance leaders can use a methodology and metrics to compare managed
      care payments against those of their local and regional peers. Depending on
      payment levels, they should adopt one of the following negotiation stances with
      payers: If payment levels are both equitable and adequate, they should view a
      continuation of the present structure as desirable. If payment levels are
      adequate but not equitable (e.g., payments are lower than payments peers are
      receiving for similar services), they should seek increases in payment to level
      the payment structure among providers. If payment levels are neither adequate nor
      equitable, they should demand correction in the near future to avoid the need to
      cease operations. If payment levels are equitable but not adequate, however, they
      should question the viability of the delivery system.

PMID- 23173371
TI  - The 50 percent solution to reducing energy costs.
AB  - Hospitals can use a five-step process to achieve energy savings: Define a minimum
      acceptable ROI or hurdle rate. Seek incentives, rebates, and tax benefits. Set a
      10-year investment horizon for all project portfolios. Create a system for
      tracking and reporting the operational and financial performance of the project
      portfolios. At the end of the year, return 50 percent of the savings to the
      facilities department and use the rest to fund additional projects.

PMID- 23173372
TI  - Road maps for the value journey.

PMID- 23173373
TI  - Cap and trade: a mechanism to reduce healthcare costs.

PMID- 23173374
TI  - Supply chain benchmarking presents opportunity for added cost savings.

PMID- 23173375
TI  - [Mortality of tuberculosis in Romania, a marker for severity of the endemic].
AB  - After reaching the lowest level of tuberculosis mortality rate in 1980, 3.7%
      hundred thousand (830 deaths), followed by a few years with low levels of
      mortality, the period following the year 1985 was marked by a gradual increase in
      the mortality rate and in 1995 it reached 11.3% hundred thousand (2560 deaths).
      The implementation since 1997 of TB control programmes on medium-term (under
      technical assistance of WHO experts) has led to a decrease in tuberculosis
      mortality rate to 1482 deaths, 6.9% hundred thousand, in 2010. Compared to
      standardized TB mortality rate in Europe, Romania is far from the countries of
      Western and Central Europe, with a rate 6.6 times greater than in the EU.
      Standardized mortality rate by sex reveals that the rate for males in Romania, in
      2009, was 6.5 times higher than in women. Similar to 2009, in 2010, the deaths
      have reached a maximum per age group at 45-54 years old. In 2010 the tuberculosis
      fatality was 4.7% and the lethality was 0.6%. Consistency of tuberculosis control
      strategy, regarding both measures for early detection of tuberculosis and
      establishing TB treatment under the direct observation, represent the safety
      elements in the reduction of tuberculosis mortality rate. It should be reminded
      that one of the goals of Stop TB Partnership is reducing mortality rate in 2012
      at half compared to 1990, Romania being one of the 18 countries included in this
      plan initiated by the WHO Europe Region Office.

PMID- 23173376
TI  - [The relevance of the 6 minutes walking test and of dyspnea measured with mMRC
      scale in evaluating COPD severity].
AB  - The 6 minutes walking test (6MW) and the measurement of dyspnoea using Medical
      Research Council modified scale (mMRC) for Chronic Obstructive Pulmonary Disease
      (COPD) allow an integrated diagnostic of severity, deficiencies and disability of
      active age, stable COPD patient, assisting the physician to create an adequate
      rehabilitation programme. The descriptive and prospective study that covered the
      period January 2008 - October 2010 aimed to determine the existing relationship
      between the dyspnoea degree, the 6 minutes walking test and the degree of
      severity of COPD patients, evaluated against GOLD stages. METHOD AND SUBJECTS: In
      a sample of 105 eligible COPD patients, aged 44 to 65, we measured the degree of
      severity of COPD using GOLD staging, mMRC dyspnea scale and 6MWT. RESULTS: The
      GOLD stages have a very strong correlation to dyspnoea degree measured by mMRC
      scale. The GOLD stages are moderately correlated with the distance covered in
      6MWT. The dyspnoea degrees are strongly correlated with the distance covered in
      the 6MWT. CONCLUSIONS: The dyspnoea degree measured by the mMRC scale allows the
      evaluation of the severity and also the disability of the COPD patient. The 6MWT
      allows the measurement of the disease severity and prognosis by the distance
      covered and also the effort endurance revealing the disability degree.

PMID- 23173377
TI  - [Non-cystic bronchiectasis: pathogenic correlations between the parameters of
      body composition, systemic inflammation and respiratory function].
AB  - The causes of bronchiectasis may be idiopathic or secondary to pulmonary
      diseases. The consequences determined by this pathology are found on different
      levels. AIM: To determine the relationships between the parameters of body mass
      composition, chronic systemic inflammatory syndrome and lung function inpatients
      with bronchiectasis. METHOD: 35 patients with bronchiectasis diagnosed through
      HRCT (High Resolution Computer Tomography) and 35 patients with COPD were
      enrolled in the study. The protocol included the testing of all subjects, not in
      an acute period, to determine body mass composition, lung function and systemic
      inflammation. RESULTS: Modified parameters of body mass composition significantly
      correlated with those determined by the presence of inflammatory syndrome and
      alteration of lung function mainly for patients with bronchiectasis compared with
      patients with COPD. CONCLUSIONS: There is an important relationship between the
      parameters that were studied and this call for an individualized and targeted
      treatment that will lead to significant improvement of the general status of
      patients with bronchiectasis.

PMID- 23173378
TI  - [Aspects of the surgical treatment in plurivisceral echinococcosis--case report].
AB  - Hydatid disease remains endemic in many parts of the world, most notably the
      Mediterranean region, Australia, New Zealand, the Middle East, and South America.
      Plurivisceral echinococcosis is defined as the concomitant or successive presence
      of hydatidosis in more than one internal organ. It has been noticed that the
      number of cases with multi-organ localizations and multiple cysts has increased
      in the last years. As the surgery of plurivisceral echinococcosis remains one of
      the challenges for the medical world, in this article we present our experience
      during 2000-2007 with this disease, followed by a case report of one of the most
      special cases of echinococcosis, discussing the principles of treatment, along
      with a new classification of this disease. Plurivisceral echinococcosis is
      associated with higher postoperative morbidity and mortality than uncomplicated
      cysts, related to organ involvement and surgical treatment. In the sequential
      approach we recommend resolving first surgically the complicated cysts or those
      at risk. In the thoracic and abdominal locations, the thoracic cysts will be
      approached first. The treatment methods will be as conservative as possible.
      Management of pulmonary and hepatic cysts (diaphragmatic side) simultaneously
      through the thoracic route is convenient and should be encouraged in patients
      because this prevents a second operation.

PMID- 23173380
TI  - Severe transfuse related acute lung injury (TRALI) syndrome in a 14 years old
      girl with a history of type I von Willebrand disease.
AB  - Von Willebrand disease (vWD) is the most common inherited bleeding disorder based
      on an autosomal abnormality of von Willebrand factor. Transfusion is a lifesaving
      medical intervention among patients with bleeding disorders. Patients with vWD
      are exposed to Transfuse Related Acute Lung Injury (TRALI) when they become
      recipients of multiple blood products and repeated transfusions. TRALI is a non
      hemolytic transfusion reaction induced by infusions of intravenous
      immunoglobulin, platelets (suspended in plasma), whole blood, cryoprecipitates,
      and fresh frozen plasma (FFP). We report a 14 years old white girl, with a
      history of type 1 von Willebrand disease (vWd), recipient of 2 units' fresh
      frozen plasma (FFP) and 1 unit whole blood transfusion who developed an acute
      respiratory distress with severe hypoxemia and bilateral pulmonary infiltrate on
      chest X-ray within 3 hours of the whole blood transfusion, completely reversible
      after mechanical ventilation. Concluding, patients with vWd who received
      recurrent transfusions have an increased risk of TRALI. Physicians must be
      familiar with it as a cause of white lung X-ray pattern.

PMID- 23173379
TI  - [Paradoxical reaction to salbutamol in an asthma patient].
AB  - Bronchial asthma is a disease with increasing incidence worldwide, being an
      important cause of morbidity and mortality. The diagnosis and management of the
      disease are subject to international guidelines, GINA being updated periodically,
      according to the latest findings about the disease. The recommendations include
      the use in all severity stages of short acting beta-2-agonists as reliever of
      asthma symptoms. We present the case of an asthma patient presenting a life
      threatening paradoxical bronchospasm at salbutamol, as well as discussions on the
      possible pathogenesis of this situation. Paradoxical bronchospasm to salbutamol
      is a rare situation but can turn into a serious problem for the patient, as well
      as for the physicians who underestimate this possibility.

PMID- 23173381
TI  - [Peripheral muscle dysfunction in chronic obstructive pulmonary disease].
AB  - Although primarily a disease of the lungs, Chronic Obstructive Pulmonary Disease
      (COPD) associates systemic manifestations and comorbidities. The skeletal muscles
      function is restricted in COPD, because of decreased endurance and strength.
      Skeletal muscle weakness has a great clinical importance in COPD, as it is
      recognized to contribute independently to poor health status, reduced quality of
      life and increased mortality. The purpose of this paper is to describe the
      current knowledge of the structural and functional abnormalities of skeletal
      muscles in COPD and the possible physiopathologic determination of these
      dysfunctions. The understanding of these abnormalities is essential in
      development of new therapeutic strategies to combat muscle dysfunction in COPD,
      including the pulmonary rehabilitation programs.

PMID- 23173382
TI  - [Non-invasive positive pressure ventilation in stable COPD: has it any role?].
AB  - The role of non invasive positive pressure ventilation in stable COPD remains, in
      many ways, a controversial subject in pulmonology. In this article we are
      analysing the pro and con arguments and select the current indications, pointing
      out the unelucidated aspects of this kind of therapy.

PMID- 23173383
TI  - Tomorrow's board leaders.
AB  - Board succession planning can improve governance performance.

PMID- 23173384
TI  - ED interventions.
AB  - Intensive case management and community support can reduce unnecessary emergency
      department visits.

PMID- 23173385
TI  - Ready for risk contracting?
AB  - Before taking on value-based care, hospitals must assess risk capacity.

PMID- 23173386
TI  - Achieving fiscal fitness.

PMID- 23173387
TI  - Transformation from the top.
AB  - Transforming a hospital's culture leads to improved patient satisfaction and
      physician loyalty.

PMID- 23173388
TI  - Community commitment.
AB  - MaineHealth adopts six metrics to assess its impact on population health.

PMID- 23173389
TI  - Stronger, smarter advocacy.
AB  - Trustees must take the lead in organizing community support for their hospitals.

PMID- 23173390
TI  - Physician whiplash.

PMID- 23173391
TI  - Managing advanced illness.
AB  - Every organization can deliver patient-centered end-of-life care.

PMID- 23173393
TI  - Political pioneer. Interview by Elizabeth Gardner.

PMID- 23173392
TI  - Exposing danger: tracking and reducing exposure is a top priority for regulators,
      providers and vendors.

PMID- 23173394
TI  - CT overuse for mild traumatic brain injury.
AB  - BACKGROUND: Multiple, validated, evidence-based guidelines exist to inform the
      appropriate use of computed tomography (CT) to differentiate mild traumatic brain
      injury (MTBI) from clinically important brain injury and to prevent the overuse
      of CT. Yet, CT use is growing rapidly, potentially exposing patients to
      unnecessary ionizing radiation risk and costs. A study was conducted to quantify
      the overuse of CT in MTBI on the basis of current guideline recommendations.
      METHODS: A retrospective analysis of secondary data from a prospective
      observational study was undertaken at an urban, Level I emergency department (ED)
      with more than 90,000 visits per year. For adult patients with minor head injury
      receiving CT imaging at the discretion of the treating physician, the proportion
      of cases meeting criteria for CT on the basis of the Canadian CT Head Rule
      (CCHR), American College of Emergency Physicians (ACEP) Clinical Policy, New
      Orleans Criteria (NOC), and National Institute for Health and Clinical Excellence
      (NICE) guidelines was reported. RESULTS: All 346 patients enrolled in the
      original study were included in the analysis. The proportion of cases meeting
      criteria for CT for each of the guidelines was: CCHR 64.7% (95% confidence
      interval [CI], 0.60-0.70), ACEP 74.3% (95% CI, 0.70-0.79), NICE 86.7% (95% CI,
      0.83-0.90), and NOC 90.5% (95% CI, 0.87-0.94). The odds ratio of the guidelines
      for predicting positive head CT findings were also reported. DISCUSSION: Some 10%
      35% of CTs obtained in the ED for MTBI were not recommended according to the
      guidelines. Successful implementation of existing guidelines could decrease CT
      use in MTBI by up to 35%, leading to a significant reduction in radiation-induced
      cancers and health care costs.

PMID- 23173395
TI  - A case-control study of an intraoperative corneal abrasion prevention program:
      holding the gains made with a continuous quality improvement effort.
AB  - BACKGROUND: Corneal injury is the most frequent ocular complication during
      general anesthesia. Although prevention has appeared feasible, inconsistent use
      and timing of conventional eye ointment and eyelid tape had failed to adequately
      prevent intraoperative corneal injuries at a department of anesthesiology in an
      academic medical center. A continuous quality improvement (CQI) program was thus
      undertaken to prevent intraoperative corneal injury. PLAN-DO-CHECK-ACT: A
      departmentwide Plan-Do-Check-Act cycle, and specifically the Seven-Step Problem
      Solving Model, were applied. The new standardized eye- protection method involved
      eye lubrication with aqueous-based gel and application of clear, square occlusive
      dressings that were large enough to cover the eyelids and surrounding skin.
      Standardized documentation of patient eye protection in the electronic anesthesia
      record was also implemented. A systematic approach maximized departmental
      awareness about this new eye-protection method and its documentation. Subsequent
      individual practitioner counseling and reinforcement was undertaken. RESULTS: A
      total of 50,151 sequential general anesthetics before and 113,044 sequential
      general anesthetics after implementation of the new corneal injury prevention
      program were analyzed. The corneal injury rate was 1.20/1,000 general anesthetics
      before versus 0.09/1,000 general anesthetics after implementing our prevention
      program (p < .001). This pattern of a marked reduction in intraoperative corneal
      injuries was sustained for the entire 45-month follow-up period. DISCUSSION: A
      simple and cost-effective method for preventing intraoperative corneal injuries
      was successfully identified, implemented, and sustained. The systematic approach
      involved a rigorous reiterative approach and resulted in a fundamental change in
      local practice pattern.

PMID- 23173396
TI  - Using process elicitation and validation to understand and improve chemotherapy
      ordering and delivery.
AB  - BACKGROUND: Chemotherapy ordering and administration, in which errors have
      potentially severe consequences, was quantitatively and qualitatively evaluated
      by employing process formalism (or formal process definition), a technique
      derived from software engineering, to elicit and rigorously describe the process,
      after which validation techniques were applied to confirm the accuracy of the
      described process. METHODS: The chemotherapy ordering and administration process,
      including exceptional situations and individuals' recognition of and responses to
      those situations, was elicited through informal, unstructured interviews with
      members of an interdisciplinary team. The process description (or process
      definition), written in a notation developed for software quality assessment
      purposes, guided process validation (which consisted of direct observations and
      semistructured interviews to confirm the elicited details for the treatment plan
      portion of the process). RESULTS: The overall process definition yielded 467
      steps; 207 steps (44%) were dedicated to handling 59 exceptional situations.
      Validation yielded 82 unique process events (35 new expected but not yet
      described steps, 16 new exceptional situations, and 31 new steps in response to
      exceptional situations). Process participants actively altered the process as
      ambiguities and conflicts were discovered by the elicitation and validation
      components of the study. Chemotherapy error rates declined significantly during
      and after the project, which was conducted from October 2007 through August 2008.
      DISCUSSION: Each elicitation method and the subsequent validation discussions
      contributed uniquely to understanding the chemotherapy treatment plan review
      process, supporting rapid adoption of changes, improved communication regarding
      the process, and ensuing error reduction.

PMID- 23173397
TI  - Using root cause analysis and form redesign to reduce incorrect ordering of HIV
      tests.
AB  - BACKGROUND: Advances in molecular biology and changes in microbial nomenclature
      may subject diagnostic microbiology to errors. A patient diagnosed with
      Pneumocystis jiroveci pneumonia and then with AIDS had received a negative "AIDS
      test"--"negative for antibodies to HTLV 1 and 2." The test requisition showed
      that the physician had requested HTLV-I/II testing but not an HIV-1/2 test. A
      root cause analysis was performed to determine if the erroneous testing
      represented a systemic problem. A study was conducted to identify and address
      such testing errors. METHODS: For the 1,952 HTLV-I/II test requests in a 17-month
      period in the Southern Alberta region, a random representative sample of 555
      requests for HTLV-I/II testing were evaluated for appropriateness. Physicians
      ordering "inappropriate" tests were surveyed to determine root causes, and the
      HTLV-I/II check box was subsequently removed from the requisition. RESULTS: Some
      318 (94%) of the 340 clinically directed HTLV tests were likely or definitely
      inappropriate--that is, only an HIV-1/2 test was required. At least 81% (127/156)
      of the 8% (156/1,948) of the HTLV-I/II tests ordered without an HIV-1/2 test
      concurrently were ordered inappropriately. In the telephone survey, all 69
      physicians suspected to have incorrectly ordered HTLV-I/II tests reported
      erroneously requesting HTLV for HIV. A root cause analysis identified confusing
      viral nomenclature, diagnostic testing menu, and form design as contributing
      factors. A requisition recall and redesign has reduced erroneous laboratory
      testing. CONCLUSIONS: A high proportion of HTLV-I/II tests were ordered
      erroneously and confused with HIV-1/2. Careful attention to routine test menus
      and form design, including the exclusion of rare and confusing pathogens, reduces
      risk of error for practicing physicians.

PMID- 23173398
TI  - Doing and documenting.

PMID- 23173399
TI  - Procedural safety in emergency care: a conceptual model and recommendations.

PMID- 23173400
TI  - [Inadequate control reduces the quality of health care].

PMID- 23173401
TI  - [2012 Nobel Prize in Physiology or Medicine. Nobel Prize for a life return
      ticket].

PMID- 23173402
TI  - [Inherited vascular fragility means a high risk of complications from surgery.
      Centralized specialist competence should support the decentralized emergency
      care].

PMID- 23173403
TI  - [Vascular complications in neurofibromatosis are life threatening. Frail vessel
      walls complicate surgical intervention--risk of iatrogenic injuries].

PMID- 23173404
TI  - [Ambulatory surgery in Sweden is structured and follows unified routines. A
      questionnaire on the practice of ambulatory surgery].

PMID- 23173405
TI  - [Congestive heart failure, part 2: treatment].

PMID- 23173406
TI  - [Is an aged physician older or younger than an old physician?].

PMID- 23173407
TI  - [Israeli physicians have to stop participating in torture].

PMID- 23173408
TI  - [Adolescence yesterday and today: care issues].
AB  - In ancient Greece, the chronological boundaries of the stages of life hinged upon
      Solon's theory of human life as divided into ten seven year stages. At the peak
      of Latin civilization, the chronological limits of the infant, pueritia and
      adulescentia were respectively 0-8 years, 8-16 years and 16-17 years, when in a
      ceremony the adolescent (a term derived from adolescente (m) present participle
      of the Latin verb adolescere = to grow) wearing the "toga of manhood" is declared
      an adult (teenager adult) and up to 30 years later iuventus. Throughout the
      following centuries, the chronological boundaries of the various ages came to
      acquire only a theoretical worth, since the child, once introduced to the world
      of work, used to suddenly become an adult. Only in the wave of Humanism in the
      XVI-XVII century, people started to rediscover the Greek 'paideia' (education),
      the Latin Humanitas' (recognition and respect towards manhood in every man), and,
      through the Christian 'caritas' (to recognize and to love the son of God in every
      man) begins a moral vision of childhood, of his weakness and innocence, a
      reflection of the 'divine purity'. In this evolution, the twentieth century
      identifies itself with adolescence, so that history moves from an era devoiced of
      adolescence to an age in which adolescence appears to be the privileged age: the
      adolescent is the hero of the twentieth century. Several and many important
      institutions have proceeded to recognize the essential rights of adolescent care
      in pediatric departments, but many are still admitted to adult wards with
      suboptimal therapeutic results, particularly for blood-cancer. The pediatrician,
      both the family one and the one in the hospital, must be the referees for the
      health of the adolescent, especially in cases of chronic diseases or in those of
      psychosocial relevance, following her in the path of the disease especially if
      other specialists are involved with a view to further investigation, and
      establishing, since early childhood, communication, dialogue and compliance with
      her and the whole family. One of the greatest philosophers and sophists of Magna
      Graecia, Gorgia of Lentini, used to state that the word has tremendous power: it
      can instill the joy, eliminate pain, enhance compassion, put an end to fear: then
      be medicine for the suffering. The doctor is in fact, in certain situations of
      life, a drug for his patient. He is the most widely used drug because drugs are
      not the only thing that matters: the soul of medicine lies in the relationship,
      in the communication between the healer and the healed.

PMID- 23173409
TI  - [The Ponseti approach for the treatment of congenital clubfoot].

PMID- 23173410
TI  - [To reduce the pain of heel prick in the newborn: comparison of six types of
      lancets].
AB  - Heel prick is an usual method performed to get a blood sample for newborn
      screening. Its wide use justifies the effort in reducing the pain as much as
      possible and some simple steps, including the use of spring heelsticks, are
      recommended by national and international guide-lines. But not all the heelsticks
      cause the same pain and allow to get enough blood for the screening. The aim of
      this work was to test six automatic heelstick devices with regard to the pain in
      heel prick measured with NIPS scale and, at the same time, to value their
      effectiveness in getting a blood sample suitable for filter paper for newborn
      screening. The following devices were assessed: Amnes Minilet Lancets, Wuxi Xinda
      Ltd, Exxe Safe Blade, Lifescan Stik Johnson & Johnson, One Touch Ultra Soft, Accu
      Chek Safe T Pro Plus. The device Exxe Safe Blade statistically differs from all
      others: it is the least painful and it doesn't need any prick repetition.

PMID- 23173411
TI  - Comparison between two treatment protocols with recombinant human erythropoietin
      (rHuEpo) in the treatment of late anemia in neonates with Rh-isoimmunization.
AB  - OBJECTIVE: [corrected] The Rh-hemolytic disease can lead to a late anemia by
      hemolytic and hyporigenerative mechanism. We compared the effectiveness of rHuEPO
      in two care protocols that differ for doses of rHuEPO administrated and for
      timing of administration. METHODS: A cohort of 14 neonates was investigated. The
      neonates were treated with two different protocols. Protocol A: a dose of 200
      U/kg/day of rHuEpo administered subcutaneously starting from the end of the
      second week of life; Protocol B: a dose of 400 U/kg/day of rHuEpo administered
      subcutaneously starting from the end of the first week of life. RESULTS: The
      hematocrit values in the protocol A group decreased during treatment (32,5% vs
      25,2%), whereas the hematocrit value in protocol B group remained almost stable
      (38,7% vs 42,8%). The mean numbers of platelets remained stable in both groups
      while neutrophils increased in protocol A group and decreased in protocol B
      (p<0,05). Reticulocyte count increased during treatment in both groups, although
      only in protocol B group it was statistically significative (p<0,05).
      CONCLUSIONS: Our results suggest a similar efficacy between the two treatment
      protocols. Increasing doses of rHuEPO do not seem enhancing their effectiveness
      and the incidence of side effects.

PMID- 23173412
TI  - [Testicular microlithiasis and Leydig cell proliferation in Wistar rats underwent
      Fowler-Stephens procedure].
AB  - OBJECTIVES: The present study investigates the outcome of Fowler-Stephens
      operation in prepubertal Wistar rats focused on microlithiasis and Leydig cell
      hyperplasia development. METHODS: Thirty-eight (38) animals underwent
      laparoscopic Fowler-Stephens operation on the right testis (8 of them formed the
      control group) and 6 of them additional contra-lateral orchectomy. The testes
      were examined histological 9,30,70 and 90 days later, while ultrasound study was
      perfomed a day earlier. RESULTS: Initially, atrophic signs were visible as early
      as 9 days after the operation. Signs of intratubular calcification were obvious
      30 days after the operation, in severe atrophic testes. Another important point
      was that in the animals that underwent orchectomy, testicular microlithiasis co
      existed with lesions of Leydig cell hyperplasia. CONCLUSIONS: Microlithiasis and
      Leydig cell hyperplasia seem to have causative relation in operated undescended
      testis and present serious postoperative complications, with a review in the
      literature.

PMID- 23173413
TI  - A distal renal tubular acidosis showing hyperammonemia and hyperlactacidemia.
AB  - INTRODUCTION: distal renal tubular acidosis (dRTA) presents itself with variable
      clinical manifestations and often with late expressions that impact on prognosis.
      CASE REPORT: A 45-day-old male infant was admitted with stopping growth,
      difficult feeding and vomiting after meals. Clinical tests and labs revealed a
      type 1 renal tubular acidosis, even if the first blood tests showed ammonium and
      lactate increase. We had to exclude metabolic diseases before having a certain
      diagnosis. CONCLUSIONS: blood and urine investigations and genetic tests are
      fundamental to formulate dRTA diagnosis and to plan follow-up, according to
      possible phenotypic expressions of recessive and dominant autosomal forms in
      patients with dRTA.

PMID- 23173414
TI  - [Renal tubular acidosis: a diagnostic and therapeutic challenge for the
      pediatrician].

PMID- 23173415
TI  - [Reconstruction of facial soft tissue defects with free flaps by microsurgery].
AB  - OBJECTIVE: To investigate the method and indications for reconstruction of facial
      complicated soft tissue defects with free flaps by microsurgery. METHODS: 37
      patients (16 males and 21 females, aged from 1 to 54 years) with different size
      of facial soft tissue defects were reconstructed with free flaps, including 10
      latissimus dorsi myocutaneous flaps, 3 thoracodorsal artery perforator flaps, 9
      scapular flaps, forearm flaps and 9 postauricular flaps. The defects size ranged
      from 1 cm x 2 cm to 25 cm x 12 cm. RESULTS: Venous obstruction happened in 3
      postauricular flaps, resulting partial necrosis in 2 flaps. All the other flaps
      survived completely. The cosmetic and functional results were both satisfactory.
      CONCLUSIONS: The facial complicated soft tissue defects can be treated
      successfully with free flaps by microsurgery. The wounds can be healed primarily
      with short recovery time and reliable cosmetic and functional result.

PMID- 23173416
TI  - [Reduction mammaplasty with central gland pedicle based on Wuringer's horizontal
      septum].
AB  - OBJECTIVE: To investigate the method and efficacy of reduction mammaplasty with
      central gland pedicle based on Wuringer' s horizontal septum in the treatment of
      female breast hypertrophy. METHODS: From Mar. 2009 to Sept. 2011, a series of 21
      consecutive patients with mild and moderate hypermastia underwent reduction
      mammaplasty with central gland pedicle. Only the mammary gland located at cranial
      portion of septum was resected and the mammary gland located at caudal portion of
      septum was preserved. RESULTS: In our series, the mean resection weight per
      breast was (327.8 +/- 148.6) g, the mean nipple-to clavicle midpoint was 20.0 cm
      (range, 18.0-22.0 cm) and the mean nipple-to-sternal-notch distance was 21.0 cm
      (range, 19.5-22.5 cm) postoperatively. Nipple was moved upward 6.5 cm on average
      (range, 4.0-10.0 cm). There was no hematoma and nipple-areolar complex (NAC)
      necrosis. Minimal wound dehiscence occurred in one case and healed by dressing
      change. 17 cases were followed up for 3 months to 2 years. Satisfactory breast
      shape was achieved with good NAC sensibility. CONCLUSIONS: The reduction
      mammaplasty with central gland pedicle based on Wuringer' s horizontal septum is
      a safe and reliable technique for mild and moderate hypermastia. Satisfactory
      breast contour, as well as NAC viability and sensibility, could be achieved with
      lower occurrence of hematoma or seroma.

PMID- 23173417
TI  - [Anatomic study and application of TRAM flap with partial preservation of
      abdominal rectus muscle in the breast reconstruction].
AB  - OBJECTIVE: To investigate the feasibility and effectiveness of transverse rectus
      abdominis musculocutaneous (TRAM) flap with partial preservation of abdominal
      rectus muscle based on the anatomic study in cadavers. METHODS: 5 adult female
      cadavers which provided by department of anatomy of Fujian Medical University
      were dissected after injection with medical red latex from the starting point of
      the inferior epigastric artery and superior epigastric artery. The TRAM flap with
      partial preservation of lateral abdominal rectus muscle were dissected for breast
      reconstruction. The location, route, branches and anastomosis of inferior and
      superior epigastric arteries were observed. Based on the anatomic study, breast
      reconstruction were performed in 8 cases with muscle-sparing TRAM flaps. RESULTS:
      The inferior epigastric artery arises from external iliac artery (9/10, 90%) or
      femoral artery (1/10, 10%) at the joint point between the internal third and
      lateral two third. There are extensive anastomoses between superior and inferior
      epigastric arteries above the umbilicus, mostly between the 2cm below the first
      tendinous intersection and umbilical level. From Sept. 2009 to Sept. 2010, 8
      cases received breast reconstruction with muscle-sparing TRAM flap. The patients
      were followed up for 3 months to one year. Fibrosis happened in subcutaneous fat
      at flap IV zone in 2 cases, borderline necrosis and subcutaneous fat liquefaction
      occurred in some areas of flap IV zone in 2 cases, which healed after
      debridement. The other 4 cases healed with no complication. Except for
      unsatisfied shape in one case, good result achieved in 7 cases. There was no
      abdominal weakness, hemia or other complication. CONCLUSIONS: It is an effective
      and safe method in breast reconstruction with muscle-sparing TRAM flap. It is
      practical with comparatively short operation time and less morbidity in donor
      site.

PMID- 23173418
TI  - [Clinical study on hemangiomas treatment with high-intensity focused ultrasound
      (60 cases)].
AB  - OBJECTIVE: To explore the clinical effect and appropriate power of high-intensity
      focused ultrasound (HIFU) in the treatment of infant hemangioma. METHODS: 80
      infants with hemangioma were randomly divided into four groups, 20 cases in each
      group. All cases in group A, B and C were irradiated on the lesion surface with 3
      5 mm/s speed for five continuous come-and-goes using HIFU, with frequency 9 MHz,
      impulse 1 000 Hz and 10% scanning overlap. The power was respectively 3.5 W in
      group A, 4.0 W in group B and 4.5 W in group C. One session contained three times
      of treatment, with one month interval. The cases in group D were only followed up
      as control group. The therapeutic effect, ulcer and scar in irradiated region in
      group A, B, C were observed 6 months after the last treatment, which were
      synchronously compared with those in group D. RESULTS: 6 months after the last
      treatment, 7, 9, 8 cases were cured and 9, 8, 10 cases were almost cured, and 4,
      3, 2 cases got improved in group A, B, C, respectively. The total effective rate
      was 100% in the three groups. While only 5 cases got improved in group D. The
      treatment effect in group A, B and C was obviously better than that in group D (P
      < 0.05), with no significant difference among the three groups statistically (P >
      0.05). Ulcer and scar in irradiated skin occurred in 0,4,6,0 cases in group A, B,
      C and D, respectively. The incidence of ulcer and scar was obviously higher in
      group B and C than that in group A and D statistically (P < 0.05). CONCLUSIONS:
      HIFU irradiating is one of effective methods for infant hemangioma treatment. The
      appropriate power should not be above 3.5 W.

PMID- 23173419
TI  - [Combined treatment with urea injection and surgical procedure for the scrotal
      vein malformation in teenagers].
AB  - OBJECTIVE: To discuss the treatment of the scrotal vein malformation in teenagers
      and clinical efficacy. METHODS: 32 cases with the local and diffuse scrotal vein
      malformation were retrospectively analyzed. 31 cases underwent local injection
      with 40% urea before resection. The urea was injected locally into tumor through
      multi-points within 30 seconds, 2-6 ml every time, one time a day. The injection
      was performed for 5-12 days. The treatment was refused in one case. The
      therapeutic effect and cosmetic result were recorded. RESULTS: The tumors were
      removed radically in 28 cases including one operation in 25 cases and secondary
      operation in 3 cases. The patients were followed up for 1-3 years with no
      recurrence. Cosmetic result with bilaterally symmetric scrotum was satisfactory.
      The tumors in 3 severe cases were partially resected with improvement.
      CONCLUSIONS: Combined treatment with urea injection and surgical procedure can
      effectively treat the scrotal vein malformation with satisfactory result.

PMID- 23173420
TI  - [Penoplasty with scrotal flap for the treatment of buried penis in children].
AB  - OBJECTIVE: To investigate the therapeutic effect of penoplasty with scrotal skin
      flap for the treatment of buried penis in children. METHODS: The narrow ring was
      cut vertically at the ventral side of penis and the prepuce inner plate was
      circularly cut 0.5 cm from the coronary sulcus. The prepuce was degloved to the
      base of penis. The abnormal aponeurosis was removed completely. The prepuce was
      designed to cover the coronary sulcus. The scrotal flaps at both sides were
      formed and advanced to cover the penile base. Then the prepuce was sutured to
      reconstruct penile-scrotal angle and scrotum plasty was completed. RESULTS: From
      March 2009 to July 2011, 24 children with buried penis were treated with scrotal
      flaps. Adhesion at external orifice of urethra was happened in two cases which
      recovered after urethra expansion. There was one case of necrosis at the distal
      end of prepuce. All the cases were followed up for 6 months to 2 years with no
      penile shrinkage. The penile appearance was good without rotation or lateral
      curvature during erection. CONCLUSIONS: The buried penis can be best corrected
      with scrotal flap. It is an ideal method with less complication.

PMID- 23173421
TI  - [Reconstruction of soft-tissue defect in the middle and distal thirds of the leg
      with the soleus muscle flap].
AB  - OBJECTIVE: To investigate the efficacy of surgical method with the soleus muscle
      flap for repairing the soft-tissue defects in the middle and distal thirds of the
      leg, combined with open tibial fracture and/or osteomyelitis. METHODS: From May
      2007 to December 2011, 8 cases with soft-tissue defects in the middle and distal
      thirds of the leg were treated with soleus muscle flaps, including 5 cases with
      chronic osteomyelitis and 3 cases with open tibial fracture and acute
      osteomyelitis. The defects size ranged from 8 cm x 6 cm to 12 cm x 10 cm. The
      surface of muscle flaps was covered by split-thickness skin graft. The defects at
      the donor site were closed directly. RESULTS: All the muscle flaps and skin
      grafts survived completely and fracture was healed. The patients were followed up
      for 2 to 54 months with satisfactory cosmetic and functional results.
      CONCLUSIONS: The soleus muscle flap is an effective and feasible method for
      reconstruction of the soft-tissue defects in the middle and distal thirds of the
      leg, combined with open tibial fracture and/or osteomyelitis. The morbidity at
      donor sites is also minor.

PMID- 23173422
TI  - [Reconstruction of traumatic ear defect by retro-auricular expanded flap and
      cartilage graft].
AB  - OBJECTIVE: To investigate the therapeutic effect of retro-auricular expanded flap
      and cartilage graft for reconstruction of traumatic ear defect. METHODS: From
      Aug. 2008 to Aug. 2010, 10 cases of traumatic ear defects were treated with retro
      auricular expanded flap and cartilage graft. The expanders (volume, 50 ml) were
      implanted subcutaneously at retro-auricular area on the first stage. Then the
      expansion began at 1 week after operation until the volume reached 60 ml. On the
      second stage, the ear defects were reconstructed with the expanded flaps, rib
      cartilage framework, as well as skin graft. RESULTS: All the wounds healed
      primarily without any complication. The patients were followed up for 6 months to
      2 years with satisfactory cosmetic results. Good symmetry was achieved.
      CONCLUSIONS: It is an effective and reliable method to reconstruct traumatic ear
      defect by retro-auricular expanded flap and cartilage graft.

PMID- 23173423
TI  - [Application of the vacuum sealing drainage technique combined with skin flap in
      chronic ulcerative wounds].
AB  - OBJECTIVE: To explore the feasibility and efficacy of the vacuum sealing drainage
      (VSD) technique combined with skin flap for the treatment of chronic ulcerative
      wounds. METHODS: From June 2009 to Aug. 2011, the VSD technique combined with
      skin flap has been applied in the treatment of 15 patients with chronic
      ulcerative wounds caused by various reasons. The VSD was applied to the wound for
      1-6 times. When infection was controlled and fresh granulation grew, skin flap
      was used to cover the wound. RESULTS: Flap necrosis happened in a small area at
      the distal end in one case, which healed after skin graft. All the other flaps
      survived with primary healing. The patients were followed up for 6-24 months
      postoperatively with no recurrence of infection. CONCLUSIONS: VSD combined with
      skin flap is an ideal choice for reconstruction of chronic ulcerative wounds. It
      has the advantages of low complications, reliable flap survival rate, and low
      infection recurrence.

PMID- 23173424
TI  - [3-Dimensional model reconstruction of penis and surrounding tissue].
AB  - OBJECTIVE: To evaluate the feasibility of 3-Dimensional (3-D) model
      reconstruction of penis and surrounding structures based on magnetic resonance
      images, which may provide the model building method for modeling surgery of
      individual penoplasty. METHODS: Magnetic resonance (MR) images of penis with
      different imaging parameters were evaluated. With the surface rendering
      construction, the 3D virtual model was established by Amira software. RESULTS:
      The anatomical details imaging is better in T2-weighted fast spin-echo images
      with 3.0 mm slice thickness. The established model based on the MR images can
      show the soft-tissue, suspensory ligament of the penis. The suspensory ligament
      stretches between the pubic symphysis and the corpora cavernosa. The penile roots
      attach to inferior ramus of pubis. CONCLUSIONS: MR imaging provides enough
      anatomical information for modeling. It can be used for the development of model
      surgery system of individual penoplasty.

PMID- 23173425
TI  - [Application of conscious sedation with midazolam, propofol and sufentanil for
      patients in plastic surgery].
AB  - OBJECTIVE: To observe the effectiveness of conscious sedation with midazolam,
      propofol and sufentanil for patients in plastic surgery. METHODS: 81 patients,
      scheduled for plastic surgery, were randomly selected to receive conscious
      sedation with midazolam 0.05 mg x kg(-1) and sufentanil 0.1 microg x kg(-1)
      intravenously, following by a continuous infusion of midazolam-propofol
      sufentanil combination (midazolam 5 mg + propofol 200 mg + sufentanil 10 microg,
      a total of 23 ml). The initial infusion rate was 0.2 ml x kg(-1) x h(-1), and was
      adjusted (in 20% of initial infusion rate increment) to maintain OAA/S score as
      11 during the operation. The patients' vital signs, discomfort and level of
      sedation were evaluated at 5 to 10 min intervals until the end of the surgery.
      The complications (i. e. anoxemia, apnea, restlessness, nausea and vomiting),
      anesthesia duration and drug consumption were recorded. The drug infusion was
      discontinued at 5 - 10 min before the end of the surgical procedure. On the first
      postoperative day, patients were asked to rate their satisfaction with the
      anesthetic management and whether they would choose to receive the same
      anesthetic technique if necessary in the future. RESULTS: The OAA/S score
      decreased from 20.0 +/- 0 to 11.9 +/- 2.6 after midazolam and sufentanil IV (P <
      0.05), and was maintained as 10.5-11.1 during the procedure. At the end of the
      procedure, the OAA/S score returned to 16.0 +/- 2.2, which was also lower
      significantly compared with baseline value (P < 0.05). The induction of sedation
      produced a significant decrease in SBP and DBP (P < 0.05) and no significant
      changes in heart rate (P > 0.05). At the end of the procedure, SBP, DBP and HR
      returned to the baseline value. The anoxemia happened in 11 cases, apnea in 5
      cases and restlessness in 2. No nausea and vomiting occurred. The anesthesia
      duration and consumption of midazolam, propofol and sufentanil were (101.1 +/-
      42.5) min, (8.4 +/- 3.7) mg, (189.1 +/- 88.7) mg and (18.2 +/- 5.6) microg
      respectively. In an interview on the first postoperative day, 96% (78/ 81) of the
      patients were satisfied with their anesthesia and were willing to receive the
      same anesthetic technique if necessary in the future. CONCLUSION: Conscious
      sedation with midazolam, propofol and sufentanil is an effective anesthetic
      technique for patients in plastic surgery.

PMID- 23173426
TI  - [Efficacy of CO2 laser combined with 32P-patch contact brachyradiotherapy for the
      treatment of keloids].
AB  - OBJECTIVE: To investigate the efficacy of CO2 laser combined with 32P-patch
      contact brachyradiotherapy for the treatment of keloids. METHODS: From 2001 to
      2006, 121 cases with 151 keloids, which reoccurred after treatment with more than
      2 methods, underwent continuous CO2 laser treatment to remove the hypertrophic
      scar tissue, following by ultra-pulse CO2 laser to treat the fresh granulation
      tissue. After wound healing, 32P-patch contact brachyradiotherapy was used for
      the lesion, 0.5-1 MBQ/cm2 for 72-96 hours, every 1-2 months. 2-3 treatment were
      applied. RESULTS: Among the 151 keloids, good result was achieved in 111 keloids,
      and effective result in 40 keloids. Adverse effect included hyperpigmentation in
      21 lesions and hypopigmentation in 32 lesions. The patients were followed up for
      2-6 years without relapse. CONCLUSION: CO2 laser combined with 32P-patch contact
      brachyradiotherapy is an effective and safe method for the treatment of
      recalcitrant keloids.

PMID- 23173427
TI  - [Experimental study on the best concentration of SVFs for promoting survival rate
      of fat graft].
AB  - OBJECTIVE: To investigate the effect of different concentrations of human adipose
      stromal vascular fraction cells (SVFs) on the survival rate of fat
      transplantation. METHODS: 0.3 ml fat tissue, derived and refined from clinical
      liposuction patients, was mixed with different concentrations of SVFs as 5 x
      10(5)/ml in Group A, or 1 x 10(6)/ml in Group B, or 2 x 10(6)/ml in Group C, or
      completely medium in control group D. Then the mixture was injected randomly
      under the back skin of 6 nude mice. The transplanted fat tissue in four groups
      was harvested at 3 months after implantation. Wet weight of fat grafts was
      measured for macroscopic aspects. After HE staining, blood vessel density, viable
      adipocytes and fibrous proliferation were counted respectively for histological
      evaluation. RESULTS: The wet weight of fat grafts in group B (81.670 +/- 7.528)
      mg was significantly higher than that in group A, C, D [(60.000 +/- 6.325) mg,
      (68.330 +/- 7.528) mg, (48.330 +/- 7.528) mg, respectively, P < 0.05)], but the
      difference between group A and group C was not statistically significant (P >
      0.05). The grafts in group A, B and C had significantly higher blood vessel
      density than those in the control group D, whereas blood vessel density was the
      highest in group B (P < 0.05) and there was no significant difference between
      group A and C (P > 0.05). Compared with group A, C and D, histological analysis
      revealed that the fat grafts in group B was consisted predominantly of adipose
      tissue with less fat necrosis and fibrosis (P < 0.05). However, fibrosis counts
      were significant lower in group A, B and C than those in group D (P < 0.05), and
      there was no significant difference between group A and C (P > 0.05).
      CONCLUSIONS: The human isolated SVFs has the advantages to improve the survival
      rate of fat transplantation, and the magnitude of 1 x 10(6)/ml is more practical
      and safe, indicating a wide clinical application in the future.

PMID- 23173428
TI  - [Progresses in anaerobic biodegradation of polycyclic aromatic hydrocarbons--a
      review].
AB  - Polycyclic aromatic hydrocarbons (PAHs) are a recalcitrant group of contaminants
      in the environment. PAHs degradation has been extensively studied and well
      understood under aerobic conditions, whereas little is known about anaerobic
      degradation of PAHs. Here, we reviewed recent progress in anaerobic degradation
      of PAHs. We focused on naphthalene and phenanthrene as model compounds. We
      addressed the main rate-limiting factors involved, including the bioaccessibility
      of PAHs, the amendment of nutrients and elector acceptors, the degrading
      microorganisms, and the biochemistry of the initial activation and subsequent
      enzyme reaction involved in the pathway. Prospects on this field are also
      discussed.

PMID- 23173429
TI  - [Molecular mechanism of co-culturing Bacillus megaterium and Ketogulonigenium
      vulgare--a review].
AB  - Co-culturing Bacillus megaterium and Ketogulonigenium vulgare is widely applied
      to 2-keto-gulonic acid production. For optimizing the process, numerous
      researchers studied on the symbiotic molecular mechanism of the co-culture
      process. The research was promoted greatly owing to omics technologies,
      bioinformatics, high throughput technologies and physiology. Recently, the
      proteomic, metabolomic, comparative genomics and transcriptomics were performed
      to the research. These omics data provided us the interaction network of the
      artificial ecosystem in multilevel. Combining with the physiological validation
      based on the high throughput method, we can elucidate the molecular mechanism in
      detail, which will facilitate us to develop strategies for metabolic engineering.
      The paper reviewed the recent developments of symbiotic molecular mechanism
      research in this co-culture process and its applications. In addition, we
      proposed the future research needs.

PMID- 23173430
TI  - [Fungal bio-control agents against ixodid tick--a review].
AB  - Entomopathogenic fungi as potential agents for bio-control have been widely
      applied in the control of insect pests in agriculture. However, the application
      remains in laboratory scale for the control of ectoparasites. Owing to the need
      to combat the short lasting period of chemical acaricides and reduction of
      pollution, it is urgent to develop sufficient, stable and safe measures for tick
      control. We reviewed the primary scientific achievements in utilization of
      environmental microbes for controlling of ticks. Studies conducted in this field
      may benefit to sustainable development, environmental protection, maintaining
      ecological balance and production of green products.

PMID- 23173431
TI  - [VPA1045 and VPA1049 of Vibrio parahaemolyticus regulate translocation of Hcp2].
AB  - OBJECTIVE: Vibrio parahaemolyticus causes acute gastroenteritis by secreting a
      number of virulence factors including two sets of type VI secretion systems
      (T6SS1 and T6SS2). However, it remains unknown how T6SS is regulated in the
      bacterium and what kinds of effects the systems have on adhesion onto and
      invasion into the host cells. This study was attempted to examine if VPA1045 and
      VPA1049 regulate T6SS2. METHODS: Vpa1045 and Vpa1049 deletion mutants were
      constructed by homologous recombination. Real-time PCR was performed to examine
      the transcription level of the translocon protein gene hcp2 in V.
      parahaemolyticus clinical strain HZ and its mutants. Western blot was used to
      analyze the levels of expression and translocation of Hcp2. RESULTS: Both VPA1045
      and VPA1049 contain the Che-Y domain, and belong to the two-component regulators.
      Deletion of either Vpa1045 or Vpa1049 did not affect expression and transcription
      of Hcp2, but decreased translocation of Hcp2 in the supernatant of V.
      parahaemolycus. Bacterial adherence to the HeLa monolayers was also significantly
      reduced as compared with their parent strains. CONCLUSION: The two-component
      regulators VPA1045 and VPA1049 regulate T6SS2 of V. parahaemolyticus post
      translationally by up-regulating Hcp2 translocation.

PMID- 23173432
TI  - [Expression and subcellular location of NSm protein of Tomato spotted wilt virus
      in plant and insect cells].
AB  - OBJECTIVE: Expression and subcellular location of NSm protein of Tomato spotted
      wilt virus were studied using plant and insect cells. METHODS: First, the NSm
      gene, located on the ambisense M RNA segment of tomato spotted wilt virus, was
      cloned into the pCHF3 vector which includes a GFP gene. Agrobacterium-mediated
      transient expression from N. benthamiana leaves was used to study the location of
      NSm in plant cells. Second, to test whether plant-specific components were
      involved in tubule formation, the NSm gene was also expressed in a heterologous
      expression system, i. e., insect cells. T. ni (Tn) cells were infected with a
      recombinant baculovirus expressing the NSm gene. RESULTS: NSm-GFP fusion proteins
      diffused in the tobacco epidermal cells and were located at the edge of the cell
      walls. These proteins can also form discontinuous green fluorescent spots at the
      plasmodesmata, which were sometimes present in pairs between two neighboring
      cells. However, GFP proteins expressed alone distributed evenly around the cell
      wall and in the nucleus. In the entomic Tn cells, NSm proteins formed a large
      number of tubular structures extending from the surface. CONCLUSION: These
      findings suggest that NSm protein target the plasmodesmata specifically in plant
      cells, and they also could form tubular structures on the surface when expressed
      in entomic Tn cells.

PMID- 23173433
TI  - [Effects of secondary structure of the leader peptide on modification and
      processing of bovicin HJ50].
AB  - OBJECTIVE: Elucidating the correlation between the secondary structure of the
      leader peptide of lantibiotic bovicin HJ50 and its modification and processing.
      METHODS: The variants with mutated leader peptide were synthesized by semi-in
      vitro biosynthesis, and their modification pattern were then analyzed by MALDI
      TOF MS. At the same time, the effect of leader peptide mutants on processing the
      modified propeptide was examined by HPLC and antimicrobial activity. RESULTS: We
      constructed 6 mutants (F-16A, V-15E, E-14L, E-8P, L-7D, L-4K) involved in forming
      secondary structure of the bovicin HJ50 leader peptide. F-16A, V-15E, L-4K showed
      very little effect on modification and processing whereas E-14L and E-8P caused
      changes in modification. In addition, we found that L-7D strongly affected the
      processing. CONCLUSION: The conserved helix structure in the leader peptide of
      bovicin HJ50 was closely related to the activity of BovM and BovT150, and the
      presence of secondary structure was very important to modification and processing
      of bovicin HJ50.

PMID- 23173434
TI  - [Denaturing gradient gel electrophoresis analysis on bacterial community change
      in the phase II composting of Volvariella volvacea substrate].
AB  - OBJECTIVE: To study the bacterial community change during the phase II composting
      of Volvariella volvacea substrate of cotton waste and to clarify the predominant
      bacteria at different composting stages. METHODS: The 16S rDNA-DGGE (denaturing
      gradient gel electrophoresis) and clone strains sequencing methods were used to
      track th change of bacterial community during composting. RESULTS: The DGGE
      profile shows that the diversity of bacteria community was rich and bands
      diversity decreased with the composting progress. The dynamic changes of
      predominant community and relative intensity were observed. The 23 predominant
      strains belong to 3 classes of Proteobacteria, Bacteroidetes and Firmicutes, 6
      families of alpha, beta, gamma-Proteobacterium, Bacteroidetes, Sphingobacteria
      and Clostridia, 11 genera, in which 19 strains were thermophilic bacteria. The
      genera of Stenotrophomonas, Comamonas, Sphingobacterium and Sinorhizobium were
      predominant bacteria in the stages of high temperature and drop of temperature
      during composting. CONCLUSION: The bacterial community structure and predominant
      community change dynamically during the phase II of Volvariella volvacea
      composting, especially in the course of entering the stage of high temperature.

PMID- 23173435
TI  - [Characterization of salicylate 5-hydroxylase for phenanthrene degradation using
      moderately halophilic Martelella sp. AD-3].
AB  - OBJECTIVE: To identify the relationship between salicylate 5-hydroxylase activity
      and the degradation rate of phenanthrene by moderately halophilic Martelella sp.
      AD-3, and to investigate their enzymatic characteristics. METHODS: The products
      resulted from degradation of salicylic acid using the crude enzyme produced by AD
      3 was analyzed using HPLC analysis, and salicylate 5-hydroxylase activities at
      different conditions was calculated according to the change of NADH absorbance at
      340 nm. RESULTS: The salicylate 5-hydroxylase activity was higher during log
      phase and early stationary phase of AD-3, and the enzyme activity was in
      consistent with phenanthrene degradation rate. The enzyme production was induced
      by phenanthrene and salicylic acid. The highest enzyme activity, 132.8 nmol/(min
      x mg), from strain AD-3 was obtained under the phenanthrene concentration of 200
      mg/L, 3% salinity and a pH of 9.0. The optimum conditions for degradation of
      salicylic acid using this enzyme were 30 degrees C , pH 7.5, and salinity 3%. The
      V(max) and K(m) for the enzyme were 200 nmol/(min x mg) and 8.7 micromol/L,
      respectively. CONCLUSION: The salicylate 5-hydroxylase was produced in the
      degradation of phenanthrene in AD-3. The enzyme activity was related to
      phenanthrene degradation rate.

PMID- 23173436
TI  - [Isolation and characterization of Thermopirellula anaerolimosa gen. nov., sp.
      nov., an obligate anaerobic hydrogen-producing bacterium of the phylum
      Planctomycetes].
AB  - OBJECTIVE: To cultivate various yet-to-be cultured heterotrophs from anaerobic
      granule sludge, we used a selective culture medium with low concentrations of
      substrates supplemented a variety of antibiotics. METHODS: An obligate anaerobic,
      thermophilic, hydrogen-producing bacterium, strain VM20-7(T), was isolated from
      an upflow anaerobic sludge blanket (UASB) reactor treating high-strength organic
      wastewater from isomerized sugar production processes. RESULTS: Cells of strain
      VM20-7(T) are non-motile, spherical, pear or teardrop shaped, occurring
      singly(o)r as aggregates (0.7 - 2.0 microm x 0.7 - 2.0 microm). Spore formation
      was not observed. Growth temperature ranges from 35 - 50 degrees C (optimum 45
      degrees C), pH ranges from 6.0 - 8.3 (optimum 7.0 - 7.5) , NaCl tolerant
      concentration ranges from 0% - 0.5% (w/v, optimum 0% ). Nitrate, sulfate,
      thiosulfate, sulfite, elemental sulfur and Fe (III)-NTA were not used as terminal
      electron acceptors. Strain VM20-7(T) utilizes a wide range of carbohydrates,
      including glucose, maltose, ribose, xylose, sucrose, galactose, mannose,
      raffinose, pectin, yeast extract and xylan. Acetate and H2 are the main end
      products of glucose fermentation. The G + C content of the genomic DNA was 60.9
      mol%. 16S rRNA gene sequence analysis revealed that it is related to the
      Pirellula-Rhodopirellula-Blastopirellula (PRB) clade within the order
      Planctomycetales (82.7 - 84.3% similarity with 16S rRNA genes of other known
      related species). CONCLUSION: The first obligate anaerobic bacterium within the
      phylum Planctomycetes was isolated with low concentration of carbohydrates and
      antibiotics. On the basis of the physiological and phylogenetic data, the name
      Thermopirellula anaerolimosa gen. nov. , sp. nov. is proposed for strain VM20
      7(T) (= CGMCC 1.5169(T) = JCM 17478(T) = DSM 24165(T)).

PMID- 23173437
TI  - [Molecular detection of symbiotic bacteria Arsenophonus from Ericerus pela
      Chavannes].
AB  - OBJECTIVE: The purpose of this study is to examine the relation between the sex
      ratio of Ericerus pela and its symbiotic bacterial Arsenophonus. METHODS: The
      symbiotic bacterial diversity in male Ericerus pela was determined through
      sequencing 16S rDNA gene library. PCR amplification for Arsenophonus was
      performed by using two 16S rDNA specific primers and 23S rDNA specific primer.
      The molecular detection of Arsenophonus in six geographic populations of E. pela,
      namely Zhaotong, Kunming, Jinkouhe, Hangzhou, Changchun, and Jianghua, were
      performed by semi-quantitative PCR. The absolute concentrations of Arsenophonus
      in E. pela of Zhaotong, Kunming, Jinkouhe geographic populations were determined
      using absolute quantitative real-time PCR. RESULTS: Two different 16S rDNA
      sequences were obtained; the sizes were 445bp and 1462bp respectively. A 23S rDNA
      sequence was obtained, the size was 582bp. Some E. pela individuals of Hangzhou
      and Jianghua were not infected with Arsenophonus. The contents of Arsenophonus in
      E. pela of Zhaotong were significantly higher than that of Kunming and Jinkouhe,
      while the contents of Arsenophonus from the latter two geographic populations
      were not significantly different. CONCLUSION: Arsenophonus is not responsible for
      the sex ratio of E. pela.

PMID- 23173438
TI  - [Diversity of C16 H33 Cl-degrading bacteria in surface seawater of the Arctic
      Ocean].
AB  - OBJECTIVE: To detect the diversity of the degradation bacteria of halogenated
      alkane form the surface seawater of the Arctic Ocean. METHOD: Twelve surface
      water samples from the Arctic Ocean were collected and enriched using C16 H33 Cl
      as the sole carbon and energy source. Bacteria from the enriched cultures were
      isolated on marine agar, and followed by 16S rRNA gene identification and
      phylogenetic analysis. Further, their degradation ability was tested with C16 H33
      Cl. The bacterial community structures were further examined by denaturing
      gradient gel electrophoresis (DGGE). RESULT: In total 112 isolates were obtained
      from the 12 samples, of which 19 isolates degraded C16 H33 Cl. Bacteria of
      Alcanivorax and Rhodococcus exerted good emulsification and degradation, whereas
      bacteria of Marinobacter also had the degradation capacity, but less. DGGE
      analysis revealed that Alcanivorax, Parvibaculum and Thioclava were dominated in
      the enriched consortia. CONCLUSION: The C16 H33 Cl degradation bacteria in the
      Arctic marine environment mainly belonged to alpha-proteobacteria, gamma
      proteobacteria, actinobacteria and bacteroidetes. This is the first report on the
      diversity of degradation bacteria of halogenated alkane in the Arctic Ocean. Our
      result contributed to the knowledge about the arctic environment and the
      biodiversity of degrading bacteria.

PMID- 23173439
TI  - [Construction of ompW knock-out mutants of Escherichia coli to increase
      sensitivity to neomycinsulphate and ampicillin].
AB  - OBJECTIVE: To investigate the contribution of an outer membrane protein OmpW to
      tolerance neomycinsulphate and ampicillin of Escherichia coli K12. METHODS: The
      ompW knock-out mutant (deltaompW) of E. coli K12 was generated using lambda-Red
      recombination system. Then the minimal inhibitory concentration (MIC) and the
      survival rates under 1/2 MIC of neomycinsulphate or ampicillin of deltaompW and
      E. coli K12 were determined respectively. RESULTS: The deltaompW was successfully
      obtained through confirmation of PCR analysis at the gene level and Western blot
      analysis at the protein level. The MIC of neomycinsulphate of deltaompW is 1.7
      microg/mL. The value is much lower than that of E. coli K12, which is 8.0
      microg/mL. Difference of survival rates under 1/2 MIC of neomycinsulphate of
      deltaompW and E. coli K12 was also observed, and their survival rates are 39% and
      98% , respectively. The MIC of ampicillin of deltaompW is 3.3 microg/mL. The
      value is also lower than that of E. coli K12 (16.0 microg/mL). The survival rates
      under 1/2 MIC ampicillin of deltaompW and E. coli K12 are 30.3% and 70.38%,
      respectively. CONCLUSION: The AompW is much more sensitive to neomycinsulphate
      and ampicillin than its parent strain. The result indicated that OmpW played
      crucial role in bacteria resistance of drug.

PMID- 23173440
TI  - [Factors affecting adhesion of Cytophaga hutchinsonii to cellulose].
AB  - OBJECTIVE: The aim of the study was to understand the mechanism of Cytophaga
      hutchinsonii adhension to cellulose. METHODS: The effects of different factors on
      the bacterial adhesion to cellulose were studied, including bacterial age, pH,
      temperature, cell surface charge, cell viability, cell surface protein,
      extracellular polysaccharides, and cellulose derivates. RESULTS: Treatments with
      heat and protease reduced the adhesion remarkably. But treatments with NaN3,
      formalin, glutaraldehyde, Congo red and NaIO4 had only slight effect on the
      adhesion. The adhension of Cytophaga hutchinsonii cells to microcrystalline
      cellulose was specific and not inhibited by cellobiose or carboxymethyl
      cellulose. CONCLUSION: The adhesion of Cytophaga hutchinsonii to cellulose was
      closely related to cell surface proteins, while cellular metabolic activity and
      extracellular polysaccharides had only slight effect on it. It is speculated that
      there might be some specific cellulose binding proteins on the cell surface.

PMID- 23173441
TI  - [Quantity of Desulfovibrios and analysis of intestinal microbiota diversity in
      health and intestinal disease people in Wuxi, Jiangsu province].
AB  - OBJECTIVE: This paper provides an overview of Desulfovibrio (DSV) incidence and
      its effect on bacterial diversity in human gastrointestinal tract of four groups:
      ulcerative colitis (UC), colorectal cancer (CRC), polypus (PP) and the healthy
      control (H). METHODS: Real time fluorescence quantitative PCR (RT-PCR) assays
      were used to enumerate DSV in gastrointestinal tract of 58 subjects. Diversity of
      gut microbiota was analyzed by PCR-Denaturing Gradient Gel Electrophoresis (PCR
      DGGE) and 16S rRNA V3 sequencing. RESULTS: RT-PCR detected DSV in all samples.
      Significantly increased numbers of DSV were observed for UC and PP groups
      compared with CRC and H groups. No significant difference was observed for CRC
      and H groups with gene copy numbers of DSV. Alterations of DSV and gut microbiota
      were observed in disease groups. CONCLUSION: We found that quantity and diversity
      of DSV are significantly increased in UC and PP compared to controls. The
      increased numbers of DSV in disease groups suggests a possible harmful role.

PMID- 23173442
TI  - [Effects of Brucella phosphoglucomutase on inducing infection of trophoblastic
      cells].
AB  - OBJECTIVE: We studied the biological function of Brucella phosphoglucomutase
      (pgm) gene, and detected the changes of human trophoblast cell invaded by the
      Brucella pgm mutant and PGM protein. METHODS: Human trophoblast cells were
      infected by the pgm mutant and PGM protein. The changes of cytokines were
      detected by enzyme-linked immunosorbent assay, and morphology of cells was
      identified. RESULTS: PGM protein was purified, and pgm mutant was constructed.
      The sera of mice immunized by pgm mutant were negative by agglutination test and
      Standard Tube Agglutination Test for Brucellosis. The cellular morphology of
      human trophoblast cells infected pgm mutant or PGM protein changed. The adhesion
      and infection of the pgm mutant reduced more than Brucella vaccine strain M5-90,
      and human trophoblast cells partially cracked off. The activity of IL-6, TNF
      alpha or lactic dehydrogenae increased in human trophoblast cells infected by the
      pgm mutant more than Brucella vaccine strain M5-90 (P < 0.01), but not for IL-10.
      Lactic dehydrogenae in human trophoblast cells infected by the PGM Protein
      increased more than sodium phosphate buffer (P < 0.01), whereas IL-6 and TNF
      alpha decreased in human trophoblast cells less than sodium phosphate buffer (P <
      0.05). CONCLUSION: The results suggest that the pgm mutant of brucella and PGM
      protein had the cytotoxic effect for human trophoblast cells with cellular
      morphology and changes of cytokines.

PMID- 23173443
TI  - [Responses of Pinus tabulaeformis forest ecosystem in North China to climate
      change and elevated CO2: a simulation based on BIOME-BGC model and tree-ring
      data].
AB  - Based on BIOME-BGC model and tree-ring data, a modeling study was conducted to
      estimate the dynamic changes of the net primary productivity (NPP) of Pinus
      tabulaeformis forest ecosystem in North China in 1952-2008, and explore the
      responses of the radial growth and NPP to regional climate warming as well as the
      dynamics of the NPP in the future climate change scenarios. The simulation
      results indicated the annual NPP of the P. tabulaeformis ecosystem in 1952-2008
      fluctuated from 244.12 to 645.31 g C x m(-2) x a(-1), with a mean value of 418.6
      g C x m(-2) x a(-1) The mean air temperature in May-June and the precipitation
      from previous August to current July were the main factors limiting the radial
      growth of P. tabulaeformis and the NPP of P. tabulaeformis ecosystem. In the
      study period, both the radial growth and the NPP presented a decreasing trend due
      to the regional warming and drying climate condition. In the future climate
      scenarios, the NPP would have positive responses to the increase of air
      temperature, precipitation, and their combination. The elevated CO2 would benefit
      the increase of the NPP, and the increment would be about 16.1% due to the CO2
      fertilization. At both ecosystem and regional scales, the tree-ring data would be
      an ideal proxy to predict the ecosystem dynamic change, and could be used to
      validate and calibrate the process-based ecosystem models including BIOME-BGC.

PMID- 23173444
TI  - [Relationships of forest fire with lightning in Daxing' anling Mountains,
      Northeast China].
AB  - Forest fire is an important factor affecting forest ecosystem succession.
      Recently, forest fire, especially forest lightning fire, shows an increasing
      trend under global warming. To study the relationships of forest fire with
      lightning is essential to accurately predict the forest fire in time. Daxing'
      anling Mountains is a region with high frequency of forest lightning fire in
      China, and an important experiment site to study the relationships of forest fire
      with lightning. Based on the forest fire records and the corresponding lightning
      and meteorological observation data in the Mountains from 1966 to 2007, this
      paper analyzed the relationships of forest fire with lightning in this region. In
      the period of 1966-2007, both the lightning fire number and the fired forest area
      in this region increased significantly. The meteorological factors affecting the
      forest lighting fire were related to temporal scales. At yearly scale, the forest
      lightning fire was significantly correlated with precipitation, with a
      correlation coefficient of -0.489; at monthly scale, it had a significant
      correlation with air temperature, the correlation coefficient being 0.18. The
      relationship of the forest lightning fire with lightning was also related to
      temporal scales. At yearly scale, there was no significant correlation between
      them; at monthly scale, the forest lightning fire was strongly correlated with
      lightning and affected by precipitation; at daily scale, a positive correlation
      was observed between forest lightning fire and lightning when the precipitation
      was less than 5 mm. According to these findings, a fire danger index based on
      ADTD lightning detection data was established, and a forest lightning fire
      forecast model was developed. The prediction accuracy of this model for the
      forest lightning fire in Daxing' anling Mountains in 2005-2007 was > 80%.

PMID- 23173445
TI  - [Water recharge through nighttime stem sap flow of Schima superba in Guangzhou
      region of Guangdong Province, South China: affecting factors and contribution to
      transpiration].
AB  - To understand the nighttime water recharge of tree through its sap flow is
      beneficial to the precise estimation of total transpiration and canopy stomatal
      conductance, and to the further understanding of the time lag between canopy
      transpiration and stem sap flow. By using Granier's thermal dissipation probe,
      this paper measured the stem sap flow of Schima superba, and synchronously
      measured the main environmental factors including air temperature, relative
      humidity, photosynthetically active radiation, and soil moisture content, and
      also analyzed the water recharge through nighttime stem flow of S. superba at
      daily and seasonal scales. The sap flow density of S. superba was lower at night
      than at daytime, and the nighttime sap flow density had a larger variation in dry
      season than in wet season. The water recharge at night generally started from
      sunset when radiation was approaching zero, and lasted up to midnight (18:00
      22:00). No significant difference was observed in the nighttime water recharge
      among seasons, and no significant correlations were found between the nighttime
      water recharge and environmental factors, but the nighttime water recharge was
      well regressed with the diameter at breast height, tree height, tree canopy size,
      stem biomass, and canopy biomass, suggesting that tree form features and biomass
      could better explain the nighttime water recharge. The contribution of nighttime
      water recharge to the total transpiration varied significantly with seasons, and
      was obviously higher in dry season than in wet season.

PMID- 23173446
TI  - [Effects of forest gap size and within-gap position on the microclimate in Pinus
      koraiensis-dominated broadleaved mixed forest].
AB  - HOBO automatic weather stations were installed in the central parts and at the
      south, north, east, and west edges of large, medium, and small gaps in a Pinus
      koraiensis-dominated broadleaved mixed forest in Xiaoxing' anling Mountains to
      measure the air temperature, relative humidity, and photosynthetic photon flux
      density (PPFD) in these locations and the total radiation and precipitation in
      the gap centres from June to September 2010, taking the closed forest stand and
      open field as the controls. The differences in the microclimate between various
      size forest gaps and between the gap centers and their edges as well as the
      variations of the microclimatic factors over time were analyzed, and the effects
      of sunny and overcast days on the diurnal variations of the microclimatic factors
      within forest gaps were compared, aimed to offer basic data and practice
      reference for gap regeneration and sustainable management of Pinus koraiensis
      dominated broadleaved mixed forest. The PPFD was decreased in the order of large
      gap, medium gap, and small gap. For the same gaps, the PPFD in gap centre was
      greater than that in gap edge. The mean monthly air temperature and total
      radiation in gap centres were declined in the sequence of July, June, August, and
      September, and the amplitudes of the two climatic factors were decreased in the
      order of open field, large gap, medium gap, small gap, and closed forest stand.
      The mean monthly relative humidity in gap centres dropped in the order of August,
      July, September, and June, and the amplitude of this climatic factor was
      decreased in the sequence of closed forest stand, small gap, medium gap, large
      gap, and open field. The total and monthly precipitations for the three different
      size gaps and open field during measurement period generally decreased in the
      order of open field, large gap, medium gap, small gap, and closed forest stand.
      In sunny days, the variations of PPFD, air temperature, and relative humidity
      were greater in large gap than in small gap, but in overcast days, it was in
      opposite.

PMID- 23173447
TI  - [Variations of canopy temperature in Quercus variabilis plantation and their
      relations with micrometeorological factors].
AB  - Based on the canopy temperature and micrometeorological data of Quercus
      variabilis in its main growth season (from May to August) in hilly areas of North
      China in 2011, this paper analyzed the variations of canopy temperature (T(c)) in
      Q. variabilis plantation and their relations with micrometeorological factors in
      typically clear days and cloudy days. From 9:00 to 17:00 in clear days, the
      boundary layer of canopy was unstable, and the mean T(c) was 3.55 degrees C
      higher than the mean air temperature (T(a)). In cloudy days, the variations of
      T(c) were gentler than those in clear days. The T(c) was significantly correlated
      with T(a), net solar radiation (R(n)), relative humidity, and wind speed, with a
      multiple correlation coefficient being 0. 825. The T(a) and R(n) were the
      dominant meteorological factors controlling T(c), and their affecting degree on
      T(c) was associated with weather condition.

PMID- 23173448
TI  - [Spectral characteristics of Pinus tabulaeformis canopy with different damaged
      rates of needle leaf in western Liaoning Province, Northeast China].
AB  - Through the measurement of the spectral reflectance of large areas Chinese pine
      (Pinus tabulaeformis Carr. ) canopy in western Liaoning Province, this paper
      analyzed the difference of the spectral reflectance of the canopies with
      different damaged rates of needle leaf. In visible band, the characteristics of
      the spectral reflectance of P. tabulaeformis canopies with healthy and damaged
      needle leaf were in accordance with the spectral characteristics of green plants,
      but the position of red valley was not obvious when the damaged rate of needle
      leaf was higher than 60%. In near-infrared band, with the decrease of the damaged
      rate of needle leaf, the canopy spectral reflectance increased at 780-1350 nm,
      but decreased at 1450-1800 and 1950-2350 nm. With the increase of the damaged
      rate, the position of red-edge inflection moved to the short-wave direction.
      There were significant correlations between the damaged rate of needle leaf and
      the red edge feature variables and some vegetation indices. The model based on
      DVI (1470, 860) could be more reliable for predicting the damaged rate of needle
      leaf in P. tabulaeformis canopy in western Liaoning Province.

PMID- 23173449
TI  - [Degradation characteristics of swamps in Zoige Plateau induced by drainage based
      on quantitative classification of vegetation].
AB  - Based on the field survey of swamp ecological characteristics and environmental
      quality and the ecological investigation of drained swamp transects in Zoige
      Plateau of Tibet in 2009, twenty typical swamp plots in the Plateau were
      classified into three types by TWINSPAN, i. e., primary swamp, long-term drained
      degraded swamp, and short-term drained degraded swamp, and each type of the
      degraded swamps was divided into three degradation grades, i. e., light
      degradation, moderate degradation, and severe degradation, with the degradation
      characteristics of vegetation and soil along the swamp degraded gradient studied.
      The swamp degradation in the Plateau was mainly driven by drainage pattern,
      drainage intensity, and soil moisture gradient, and the vegetation degradation
      was more obvious than the soil degradation. In the vegetation degradation, the
      structural change of hydro-type functional assemblage was most obvious, e. g.,
      the importance value of helophytes under the stress of long-term drainage and
      short-term drainage decreased from 0.920 to 0.183 and 0.053, while that of
      mesophytes increased from 0.029 to 0.613 and 0.686, respectively. The soil
      response to the swamp degradation was in hysteresis, i. e., the soil physical and
      chemical properties presented definite variations but the differences were not
      significant among the swamps with different grades of degradation. The results of
      CCA indicated that soil moisture and nitrogen and potassium contents were the
      most important factors affecting the plant species distribution in drained
      degraded swamps in Zoige Plateau.

PMID- 23173450
TI  - [Effects of NaCl stress on leaf photosynthesis characteristics and free amino
      acid metabolism of Heyedysarum scoparium].
AB  - This paper studied the variations of leaf photosynthesis gas exchange,
      chlorophyll fluorescence, and free amino acid contents of Heyedysarum scoparium
      under the stress of different concentration NaCl, aimed to understand the effects
      of salt stress on the leaf physiological characteristics and free amino acid
      metabolism of the plant. Under mild salt stress, the photo-damage of the leaf
      photosystem II was avoided via the dissipation of excess excitation energy, and
      stomatal limitation was the main factor reducing the photosynthesis rate. With
      the increase of salt stress, the leaf photoprotection was not sufficient to avoid
      oxidative damage, and thus, the damage to photosystem II happened. Under the
      stress of 200 mmol NaCl x L(-1), non-stomatal limitation was the main factor
      responsible for the inhibition of photosynthesis. The accumulation and metabolism
      of major free amino acids in H. scoparium leaves varied under salt stress. Under
      mild salt stress, the major free amino acids such as proline, glutamate,
      aspartate, and alanine had a significant accumulation, but with the further
      increase of salt stress, the aspartate and alanine contents in H. scoparium
      leaves decreased, while the synthesis and accumulation of praline increased.

PMID- 23173451
TI  - [Effects of light intensity on the phenotypic plasticity of invasive species
      Ambrosia trifida].
AB  - Through artificial shading, this paper studied the phenotypic plasticity of
      invasive species Ambrosia trifida in its morphology, biomass allocation, and
      photosynthesis characteristics in response to different light intensities. As
      compared with the control, shading increased the stem height, crown width, leaf
      area, specific leaf area, and the proportion of leaf biomass in total biomass of
      A. trifida significantly, but decreased the total biomass, biomass per unit leaf
      area, and root to shoot ratio. Under natural light condition, the crown width and
      leaf area were smaller and the root to shoot ratio was larger, which benefited
      the decrease of water loss under high temperature and high light intensity and
      manifested the stronger phenotypic plasticity of A. trifida in its morphology and
      biomass allocation in response to different light intensities. Under shading, the
      mean daily net photosynthetic rate, transpiration rate, and stomatal conductance
      decreased, while the stomatal CO2 concentration increased. At noon when the light
      intensity was the highest, the photosynthetic rate, transpiration rate, and
      stomatal conductance under low shading reached the maximum. Under moderate
      shading and high shading, the chlorophyll content increased significantly, and
      the chlorophyll a/b had a significant decrease, which could improve the
      utilization of light energy by A. trifida under shading environment.

PMID- 23173452
TI  - [Role of mitochondrial alternative oxidase (AOX) pathway in photoprotection in
      Rumex K-1 leaves].
AB  - Taking Rumex K-1 leaves as test materials, this paper studied the role of
      mitochondrial alternative oxidase (AOX) pathway in photoprotection under
      different light intensities. Under low light intensity (200 micromol x m(-2) x s(
      1)), and after treated with salicylhydroxamic acid to inhibit the AOX pathway,
      the leaf actual photochemical efficiency of PS II, linear electron transport rate
      of photosynthesis, and photosynthetic O2 evolution rate all decreased
      significantly while the non-Q(B) reducing reaction center had a significant
      increase, indicating that under low light, the photoinhibition was aggravated
      while the scavenging enzymes of reactive oxygen species (ROS) increased, which
      avoided the over-accumulation of ROS and partially alleviated the photoinhibition
      of Rumex K-1 leaves. Under high light intensity (800 micromol x m(-2) x s(-1)),
      the inhibition of AOX pathway caused more severe photoinhibition, and the
      increased activities of ROS scavenging enzymes were insufficient to prevent the
      over-accumulation of ROS. This study demonstrated that AOX pathway played an
      important role in the photoprotection in Rumex K-1 leaves under both high and low
      light intensities, and the role of AOX pathway in photoprotection under high
      light could be irreplaceable by the other photoprotection pathways in
      chloroplast.

PMID- 23173453
TI  - [Effects of snow pack removal on soil microbial biomass carbon and nitrogen and
      the number of soil culturable microorganisms during wintertime in alpine Abies
      faxoniana forest of western Sichuan, Southwest China].
AB  - To understand the effects of the lack of snow pack under global warming on the
      characteristics of soil microorganisms during wintertime, a snow-shading
      experiment was conducted in a primary fir (Abies faxoniana) forest after snow
      pack removal, with the soil microbial biomass carbon (MBC) and nitrogen (MBN) and
      soil culturable microorganisms (bacteria and fungi) at the stages of snow
      forming, snow covering, and snow melting investigated. Snow pack removal had
      significant effects on the soil MBC and MBN and the number of soil culturable
      bacteria and fungi, but the responses of the culturable microorganisms differed
      with the stages of snow-shading. Under the condition of snow pack removal, the
      MBC and MBN in soil organic layer decreased significantly at the early stages of
      snow forming and snow melting but increased significantly at snow covering stage
      and at the later stage of snow melting, and the number of culturable bacteria
      decreased significantly from the early stage of snow forming to the stage of snow
      covering while that of culturable fungi had a significant increase from the early
      stage of snow forming to the stage of snow melting. After snow melting, the MBC
      and the number of culturable fungi in soil organic layer had a significant
      decrease, the number of cultural bacteria was in adverse, but the MBN had less
      change. The MBC and MBN and the number of culturable microorganisms in soil
      mineral layer had the similar variation trends as those in soil organic layer,
      but the fluctuations were smaller. It was suggested that snow pack removal
      changed the ratio of culturable bacteria to culturable fungi, showing positive
      effects on the number of soil culturable fungi during wintertime in alpine Abies
      faxoniana forest of western Sichuan.

PMID- 23173454
TI  - [Effects of Morus alba and Setaria italica intercropping on their plant growth
      and diurnal variation of photosynthesis].
AB  - A field investigation was conducted to study the effects of intercropping Morus
      aIba and Setaria italica on their dry matter production, land use efficiency, and
      diurnal variation of leaf photosynthesis. Under intercropping, the plant height,
      basal diameter, root length, and branch number of M. alba increased by 6.0%,
      13.7%, 6.8%, and 14.8%, respectively, and the leaf yield of M. alba was increased
      by 31.3%, as compared with monoculture M. alba. In contrast, the plant height and
      root length of intercropped S. italica had no significant difference with those
      of monoculture S. italica. Intercropping enhanced the equivalent ratio and use
      efficiency of arable land. For both M. alba and S. italica in monoculture or
      intercropping, their leaf photosynthetic depression all occurred at midday (12
      :00), but the leaf photosynthetic depression of monoculture M. alba was heavier
      than that of intercropped M. alba. Intercropping promoted the leaf stomatal
      conductance (g(s)) and water use efficiency (WUE) of M. alba at midday, increased
      the photosynthetic carbon assimilation of M. alba, and inhibited the decline of
      M. alba leaf actual photochemical efficiency of PS II (phi(PS II)),
      photosynthetic electron transport rate (ETR), and the maximal photochemical of PS
      II (F(v)/F(m)) , which might contribute to alleviate the leaf photosynthetic
      depression of M. alba at midday. It was concluded that M. alba and S. italica
      intercropping could obviously improve the leaf photosynthetic capacity of M.
      alba.

PMID- 23173455
TI  - [Effects of mulberry-soybean intercropping on carbon-metabolic microbial
      diversity in saline-alkaline soil].
AB  - Aiming at the characteristics that mulberry-soybean intercropping could alleviate
      the damage of saline-alkaline soil, Biolog technique was adopted to study the
      effects of this intercropping on the diversity of carbon-metabolic microbial
      community in the rhizosphere of saline-alkaline soil. Under mulberry-soybean
      intercropping, the average well color development (AWCD) symbolizing the
      metabolic activity of soil microbes was obviously higher, as compared with that
      under mulberry or soybean monocropping, being the lowest under mulberry
      monocropping. The McIntosh index was also higher under intercropping than under
      monocropping, but the Shannon index and Simpson index had less difference between
      intercropping and monocropping, indicating that intercropping changed the
      composition and enhanced the diversity of the microbial community in the
      rhizosphere of saline-alkaline soil. Principal component analysis (PCA) showed
      that the carbon source utilization mode of the soil microbial community differed
      between intercropping and monocropping, and the main carbon sources were
      carbohydrate, carboxylic acid, and polymers. Soil pH and salinity were the main
      factors limiting the diversity of the microbial community in saline-alkaline
      soil, and intercropping could effectively decrease the soil pH and salinity and
      promote the improvement of soil microbial community diversity.

PMID- 23173456
TI  - [Differences in root developmenly of winter wheat cultivars in Huang-Huai Plain,
      China].
AB  - Selecting one presently popularized winter wheat cultivar (Zhengmai 9023) and two
      cultivars (Abo and Fengchan 3) introduced in the 1950s and 1960s in Huang-Huai
      Plain as test materials, and by using minirhizotron technique, this paper studied
      the live root length, root diameter distribution, and net root growth rate of the
      cultivars. Fine roots with a diameter from 0.05 mm to 0.25 mm occupied the
      majority of the whole root system, and the fine roots with a diameter less than
      0.5 mm accounted for 98% of the live root length. The average root diameter
      varied with plant growth, the variation range being 0.15 - 0.22 mm, and no
      significant difference was observe among the cultivars. The live root length was
      significantly positively correlated root number, suggesting that root number was
      the main factor for the increase of live root length. The most vigorous growth
      period of the roots was from reviving to jointing stage, and Abo and Fengchan 3
      had a longer period increased root vitality, as compared with Zhengmai 9023. For
      Zhengmai 9023, its fine roots with a diameter more than 0.1 mm had an increasing
      proportion after jointing stage, which was helpful for improving plant
      resistance, root activity, and grain-filling at late growth stages.

PMID- 23173457
TI  - [Effects of planting density on root spatiotemporal distribution and plant
      nitrogen use efficiency of winter wheat].
AB  - Taking winter wheat cultivars Tainong 18 (TN18) and Shannong 15 (SN15) as test
      materials, a field experiment was conducted to study the effects of planting
      density (135 x 10(4), 270 x 10(4), and 405 x 10(4) plants x hm(-2) for TN18;
      172.5 x 10(4), 345 x 10(4), and 517.5 x 10(4) plants x hm(-2) for SN15) on the
      root spatiotemporal distribution and plant nitrogen use efficiency of the
      varieties. For TN18, its root length density, total root absorbing area, and
      active root absorbing area increased with increasing planting density, and peaked
      at planting density 405 x 10(4) plants x hm(-2) during the whole growth period.
      For SN15, its root length density, total root absorbing area, and active root
      absorbing area achieved the highest values at planting density 345 x 10(4) plants
      x hm(-2) at booting and late grain-filling stages. The grain yield, nitrogen
      uptake efficiency, nitrogen partial factor productivity, and nitrogen use
      efficiency of TN18 were the highest at planting density 405 x 10(4) plants x hm(
      2), and those of SN were the highest at planting density 345 x 10(4) plants x hm(
      2) but had less differences between the densities 345 x 10(4) and 517.5 x 10(4)
      plants x hm(-2). The inorganic nitrogen accumulation in different soil layers
      decreased with increasing planting density at maturity stage. Taking grain yield
      and nitrogen use efficiency into consideration, the appropriate planting density
      of TN18 and SN15 would be 405 x 10(4) and 345 x 10(4) plants x hm(-2),
      respectively.

PMID- 23173458
TI  - [Dynamic changes of photosynthetic characteristics in big-spike wheat yield
      formation].
AB  - A field experiment was conducted to investigate the yield traits, leaf
      photosynthetic rate, chlorophyll fluorescence parameters, chlorophyll content
      (Chl), and leaf area index (LAI) of eight new big-spike wheat lines, with
      multiple-spike cultivar Xinong 979 (Triticum aestivum cv. Xinong 979) as the
      control. The eight new lines had significantly higher kernel numbers per spike,
      kernel qualities, and 1000-grain mass but lower spike numbers per unit area, and
      the lines 2036, 2037, 2038, and 2040 had significantly higher yields than the
      control. The average net photosynthetic rate (P(n)) of the eight new lines had no
      significant difference with that of the control, but the PS II maximum energy
      conversion efficiency, PS II actual photochemical efficiency, photochemical
      quenching coefficient, and PS II reaction center activity of the lines were
      higher than those of the control. The leaf Chl of the lines 2037, 2040, 2039,
      2038 and 2036 were 17.5%, 19.1%, 15.3%, 13.9%, and 7.9% higher than those of the
      control, and their LAI was significantly higher than that of the control and
      declined slowly in late growth period.

PMID- 23173459
TI  - [Effects of seeding-box total fertilization on rice yield and nitrogen loss].
AB  - By using seeding-box total fertilization technology, a two-year field plot
      experiment was conducted to study the effects of applying medium rate of
      controlled-release urea fertilizer (MN, 80 kg N x hm(-2)), high rate of
      controlled-release urea fertilizer (HN, 120 kg N x hm(-2)), and conventional urea
      fertilizer (FP, 300 kg N x hm(-2)) on rice yield and nitrogen loss. As compared
      with FP, HN did not decrease rice yield significantly, and MN and HN increased
      the two-year average nitrogen use efficiency (NUE) by 26.2% and 20.7%,
      respectively (the NUE in treatment FP was 33.2%). In treatment FP, the total N
      concentration in surface water peaked after 1-3 days of urea application; while
      in treatments MN and HN, the total N concentration in surfate water peaked after
      7-9 days of urea application, and was significantly lower than that in treatment
      FP throughout the rice growth period. The nitrogen leaching loss in treatment FP
      mainly occurred at tillering stage, while that in treatments MN and HN delayed to
      tillering-flowering stage. In all treatments, the NO3(-)-N loss accounted for
      59.7% - 64.2% of the total N loss. HN decreased the total N leaching loss by
      51.8%, as compared with FP.

PMID- 23173460
TI  - [Effects of plant polysaccharide compound agents on the photosynthetic
      characteristics and dry matter of soybean].
AB  - A field experiment was conducted to study the effects of foliar spraying three
      compound agents [plant polysaccharides (P1), plant polysaccharides and 5
      aminolevulinic acid (P2), and plant polysaccharides and 5-aminolevulinic acid and
      dimethylpiperidinium chloride (P3)] at the initial flowering stage of soybean on
      its leaf chlorophyll content, photosynthesis and transpiration, dry matter
      accumulation and allocation, and grain yield. Within 35 days after spraying the
      three compound agents, the leaf chlorophyll content had obvious increase, and its
      decreasing trend with plant growth had somewhat delay. Compared with the control,
      spraying P1 and P3 increased the leaf photosynthetic rate and water use
      efficiency by more than 13.2% and 10.3%, respectively. With the spraying of the
      three compound agents, the dry matter accumulation in aerial part increased, and
      the allocation of dry matter from leaf to pod was also enhanced, with the
      contribution of post-anthesis assimilates to grain yield increased by more than
      17.1%. The 100-grain mass and the pods and seeds per plant increased
      significantly after spraying P1 and P3, but had no significant increase after
      spraying P2. The grain yield of soybean treated with the three compound agents
      increased by more than 5.9%, compared with the control. This study showed that
      the three plant polysaccharide compound agents could increase the leaf
      chlorophyll content, delay the leaf-senescence, improve the leaf photosynthetic
      capacity and water status, effectively control the dry matter accumulation and
      post-anthesis assimilates allocation, and increase the grain yield of soybean.

PMID- 23173461
TI  - [Greenhouse tomato transpiration and its affecting factors: correlation analysis
      and model simulation].
AB  - A pot experiment was conducted to study the correlations between the daily
      transpiration of greenhouse tomato and the related affecting factors such as
      total leaf area per plant, soil relative moisture content, air temperature,
      relative humidity, and solar radiation under different treatments of
      supplementary irrigation. A regression model for the daily transpiration of
      greenhouse tomato was established. There existed significant linear correlations
      between the daily transpiration and the test affecting factors, and the affecting
      factors had complicated mutual effects. Soil relative moisture content was the
      main decision factor of the transpiration, with the decision coefficient being
      27.4%, and daily minimum relative humidity was the main limiting factor, with the
      decision coefficient being -119.7%. The square value of the regression
      coefficient (R2) between the predicted and measured tomato daily transpiration
      was 0.81, root mean squared error (RMSE) was 68.52 g, and relative prediction
      error (RE) was 19.4%, suggesting that the regression model established by using
      the main affecting factors selected through path analysis could better simulate
      the daily transpiration of greenhouse tomato.

PMID- 23173462
TI  - [Characteristics and adaption of seasonal drought in southern China under the
      background of global climate change. I. Change characteristics of precipitation
      resource].
AB  - Based on the 1959-2008 precipitation data from 262 meteorological stations in
      southern China, this paper analyzed the change characteristics of seasonal
      precipitation trend coefficient, precipitation variability, and annual and
      decadal precipitation standardized anomalies in this region. In the study period,
      there was a great difference among the trend of quarter precipitation. In most
      parts of the region, the precipitation in spring and autumn presented a
      decreasing trend but that in summer and winter was in adverse; only in southwest
      part, a slightly different trend was observed. In the whole region, the
      probability of spring drought decreased, but that of summer drought, autumn
      drought, and winter drought increased. Spring drought often occurred in south and
      southwest parts, summer drought and autumn drought often occurred in south part
      and the middle, lower reaches of Yangtze River, and winter drought expanded from
      south part to south part and the middle, lower reaches of Yangtze River. The
      precipitation in spring and autumn was below the normal level after the 1980s,
      while that in summer and winter was below the normal level before the 1990s,
      above the normal level in the 1990s, and below the normal level since the 21st
      century. The decadal change of the seasonal precipitation standardized anomaly in
      each part of the region was basically consistent, i. e., decreased in autumn and
      increased in summer and winter.

PMID- 23173463
TI  - [New paradigm for soil and water conservation: a method based on watershed
      process modeling and scenario analysis].
AB  - With the increase of severe soil erosion problem, soil and water conservation has
      become an urgent concern for sustainable development. Small watershed
      experimental observation is the traditional paradigm for soil and water control.
      However, the establishment of experimental watershed usually takes long time, and
      has the limitations of poor repeatability and high cost. Moreover, the
      popularization of the results from the experimental watershed is limited for
      other areas due to the differences in watershed conditions. Therefore, it is not
      sufficient to completely rely on this old paradigm for soil and water loss
      control. Recently, scenario analysis based on watershed modeling has been
      introduced into watershed management, which can provide information about the
      effectiveness of different management practices based on the quantitative
      simulation of watershed processes. Because of its merits such as low cost, short
      period, and high repeatability, scenario analysis shows great potential in aiding
      the development of watershed management strategy. This paper elaborated a new
      paradigm using watershed modeling and scenario analysis for soil and water
      conservation, illustrated this new paradigm through two cases for practical
      watershed management, and explored the future development of this new soil and
      water conservation paradigm.

PMID- 23173464
TI  - [Improvement of "scatter degree" method and its application in evaluating river
      ecosystem health].
AB  - "Scatter degree" method is generally blamed for not capable of reflecting the
      subjective information of evaluator in comprehensive evaluation and for the
      complexity, uncertainty, and variety of the factors affecting river ecosystem
      health. In this paper, the "scatter degree" method was improved and applied to
      comprehensively evaluate the ecosystem health status of the upstream, midstream,
      and downstream of Beiyunhe River which flowed through Beijing and Tianjing. The
      ecosystem health value of upstream, midstream, and downstream was evaluated as
      0.539, 0.521 and 0. 546, respectively, indicating that these streams were in sub
      health condition. The environmental status of flowing water was the most
      important factor affecting the River' s ecosystem health. With the application of
      the improved method to evaluate river ecosystem health, both the evaluator' s
      subjective judgment and the data's objective information could be included, the
      evaluation process was transparent, and the evaluation results were scientific,
      reasonable, objective, and reliable, suggesting that this method could be served
      as a technical support and a basis for the comprehensive treatment of rivers.

PMID- 23173465
TI  - [Spatiotemporal variation of vegetation in northern Shaanxi of Northwest China
      based on SPOT-VGT NDVI].
AB  - By using 1998-2010 SPOT-VGT NDVI images, this paper analyzed the spatiotemporal
      variation of vegetation in northern Shaanxi. In 1998-2010, the NDVI in northern
      Shaanxi had an obvious seasonal variation. The average monthly NDVI was the
      minimum (0.14) in January and the maximum (0.46) in August, with a mean value of
      0.28. The average annual NDVI presented an overall increasing trend, indicating
      that the vegetation in this area was in restoring. Spatially, the restoration of
      vegetation in this area was concentrated in central south part, and the
      degradation mainly occurred in the north of the Great Wall. Air temperature and
      precipitation were the important climate factors affecting the variation of
      vegetation, with the linear correlation coefficients to NDVI being 0.72 and 0.58,
      respectively. The regions with better restored vegetation were mainly on the
      slopes of 15 degrees-25 degrees, indicating that the Program of Conversion of
      Cropland to Forestland and Grassland had a favorable effect in the vegetation
      restoration in northern Shaanxi.

PMID- 23173466
TI  - [Secondary productivity of macrobenthos in intertidal flat of Luoyuan Bay, Fujian
      Province of East China].
AB  - Based on the survey data of macrobenthos in the intertidal flat of Luoyuan Bay in
      2009, and by using Brey' s empirical formula, this paper estimated the
      macrobenthos secondary productivity, production/biomass (P/B) ratio, and their
      spatiotemporal distribution patterns in the flat. The annual secondary
      productivity and P/B ratio of the macrobenthos in the flat were estimated as
      18.58 g AFDM (ash free dry mass) x m(-2) x a(-1) and 0.97, respectively, and the
      secondary productivity in the Spartina alterniflora marshes of the upper
      intertidal flat (8.97g AFDM x m(-2) a(-1)) was much lower than that in the bare
      flat of the lower intertidal zone (28.19 g AFDM x m(-2) x a(-1)). Since the
      introduction of S. alterniflora by the end of the 1980s, the secondary
      productivity of the macrobenthos in the flat had increased about 4 folds.
      Musculus senhousei, which inhabited in the lower bare flat, contributed 66.4% of
      the total macrobenthos secondary productivity in the entire intertidal flat. If
      the contribution from M. senhousei was not taken into account, the macrobenthos
      secondary productivity in the salt marshes would be significantly higher than
      that in the bare flat, and the macrobenthos secondary productivity in the
      intertidal flat would have less change. The successful colonization of M.
      senhousei was partly attributed to the changes of sediment composition enhanced
      by S. alterniflora due to its capability in trapping fine-grained materials; this
      species' feeding activities result in a remarkable increase of sediment
      chlorophyll a content. There was a significant positive correlation between the
      secondary productivity of macrobenthos and the sediment chlorophyll a and/or
      organic matter contents. These findings suggested that salt marshes had effects
      on the coastal wetland ecosystem via a number of physical and biological
      mechanisms.

PMID- 23173467
TI  - [Physiological responses of Enteromorpha linza and Enteromorpha prolifera to
      seawater salinity stress].
AB  - To investigate the physiological responses and adaptation mechanisms of
      Enteromorpha to seawater salinity stress, a laboratory experiment with
      Enteromorpha linza and E. prolifera was conducted to study their fresh mass (FM),
      relative growth rate (RGR), relative electrical conductivity (REC), chlorophyll
      (Chl) and carotenoid (Car) contents, Chl a/Chl b, Chl/Car, chlorophyll
      fluorescence parameters, and osmotic adjustment ability (OAA) under the stress of
      different salinity levels of diluted and concentrated seawater for 10 days.
      Compared with the control, 10%-200% salinity seawater increased the FM and RGR of
      the two Enteromorpha species obviously, 100% and 50% salinity seawater made the
      FM and RGR of E. linza and E. prolifera peaked, respectively, while 300% salinity
      seawater decreased the FM and RGR of E. linza and E. prolifera significantly,
      with the decrement being larger for E. linza. The biomass of E. linza and E.
      prolifer only had an increase in 50% and 100% sanity seawater and in 10%, 50%,
      100%, and 200% salinity seawater, respectively. The Chl and Car contents and Chl
      a/Chl b of E. linza and E. prolifera had a significant increase in 10% salinity
      seawater, but decreased after an initial increase with the increasing salinity
      level of seawater. The Chl and Car contents and Chl a/Chl b of E. linza and E.
      prolifera peaked in 100% and 50% salinity seawater, respectively. With increasing
      salinity of seawater, the light use efficiency (alpha), maximal photochemical
      efficiency of PS II (F(v)/F(m)), actual photochemical efficiency of PS II in the
      light (Yield), maximal relative electron transport rate (rETR(max)), and half
      saturation light intensity (I(k)) of E. linza and E. prolifera all showed the
      same variation trend as Chl. 10% -300% salinity seawater enabled E. linza and E.
      prolifera to express certain osmotic adjustment ability (OAA), and the OAA of E.
      linza and E. prolifer peaked in 100% and 50% salinity seawater, respectively. The
      growth of Enteromorpha had no correlation with Chl/Car, but was significantly
      negatively correlated with REC and positively correlated with Chl, Car, Chl a/
      Chl b, F(v)/F(m), Yield, rETR(max), alpha, I(k), and OAA. To sum up, 100%
      salinity was the optimal salt concentration for the growth of E. linza, and 50%
      salinity was optimal for E. prolifera. E. prolifera could adapt to a wider range
      of salinity than E. linza. The parameters REC, Chl, Car, Chl a/Chl b, F(v)/F(m),
      Yield, rETR(max), alpha, I(k), and OAA could be used to evaluate the salt
      adaptation of Enteromorpha.

PMID- 23173468
TI  - [Microbial biomass and its correlations with carbon, nitrogen, and phosphorus in
      the sediments of Taihu Lake].
AB  - To explore the responses and feedbacks of the microbes in the sediments of Taihu
      Lake to the sediment nutrients, an investigation was made on the microbial
      biomass carbon (MB(C)), microbial biomass nitrogen (MB(N)), microbial biomass
      phosphorus (MB(P)), and their correlations with the total organic carbon (TOC),
      total nitrogen (TN), and total phosphorus (TP) in the sediments. The microbial
      biomass in the sediments was 184.66 mg x kg(-1), being higher at the lakeside
      than in the mid-lake region. The MB(C) was higher in the western coastal region,
      Zhushan Bay, and Meiliang Bay, with an average of 127.57 mg x kg(-1), MB(N) was
      higher in Meiliang Bay, Gonghu Bay, mid-lake region close to Meiliang Bay and
      Gonghu Bay, and eastern costal region, with an average of 19.25 mg x kg(-1), and
      MB(P) was higher in the eastern region and parts of the mid-lake region, with an
      average was 19.09 mg x kg(-1). The TOC high value zone (> or = 2.30 g x kg(-1))
      was mainly in Zhushan Bay, western coastal region, Meiliang Bay, and Gonghu Bay,
      with an average of 1.59 g x kg(-1), TN high value zone (> or = 0.30 g x kg(-1))
      was mainly in the Gonghu Bay, Meiliang Bay, Zhushan Bay, and western costal
      region, with an average of 0.21 g x kg(-1), and TP high value zone (> or = 1.20 g
      x kg(-1)) was mainly in the eastern coastal region and parts of the mid-lake
      region, with an average of 0.55 g x kg(-1). The TOC/TN ratio in the sediments was
      7-19, with an average of 8.97, which showed that the organic substances in the
      sediments had obvious dual sources, among which, terrestrial organisms were
      mainly in the west side of the lake. The microbial biomass in the sediments was
      significantly positively correlated with sediment TOC and TN but had less
      correlation with sediment TP, and the MB(C)/MB(N) was significantly correlated
      with sediment TOC/TN, suggesting that the microbes in the sediments of Taihu Lake
      were mainly affected by the sediment TOC and TN, and the changes of the TOC/TN
      had significant effects on the microbial community structure.

PMID- 23173469
TI  - [Effects of temperature on population parameters of Therioaphis trifolii (Monell)
      (Homoptera: Aphididae)].
AB  - To investigate the effects of temperature on the population growth of Therioaphis
      trifolii (Monell) (Homoptera: Aphididae), a laboratory experiment was conducted
      to study the development, reproduction, and life table of the spotted alfalfa
      aphid at nine constant temperatures ranged from 15 to 35 degrees C. The aphid
      could not survive at 35 degrees C. The total nymphal period shortened
      significantly with increasing temperature. From birth to adult stage, it required
      18.33 days at 15 degrees C, but only 4.02 days at 32 degrees C. The survivorship
      of the nymphs ranged from 40.0% (32 degrees C) to 83.6% (25 degrees C). The
      average longevity of the adults ranged from 10.64 days at 32 degrees C to 20.87
      days at 23 degrees C. The reproductive peak was advanced with increasing
      temperature, and the reproduction duration at all test temperatures was 3-6 days
      except that at 15 degrees C (15 days). The average fecundity and the highest
      fecundity were the highest at 25 degrees C, being 82.0 and 149.0 offspring per
      female aphid, respectively. When the temperature increased, the mean generation
      time was gradually decreased from 31.17 days at 15 degrees C to 10.17 days at 32
      degrees C. The net reproductive rate was the highest (68.62) at 25 degrees C and
      the lowest (13.96) at 32 degrees C. The intrinsic rate of increase was 0.10-0.30
      per day, with the highest at 28 degrees C but the lowest at 15 degrees C. The
      developmental threshold temperature and thermal constant of the nymphs were 9.35
      degrees C and 97.83 day-degrees, respectively. Unary quadratic equation could be
      used to describe the relationships of the fecundity, net reproductive rate, and
      intrinsic growth rate with the temperature.

PMID- 23173470
TI  - [Resistance mechanisms and cross-resistance of phoxim-resistant Frankliniella
      occidentalis Pergande population].
AB  - To understand the resistance risks of Frankliniella occidentalis Pergande against
      phoxim, this paper studied the resistance mechanisms of phoxim-resistant F.
      occidentalis population against phoxim and the cross-resistance of the population
      against other insecticides. The phoxim-resistant population had medium level
      cross-resistance to chlorpyrifos, lambda-cyhalothrin, and methomyl, low level
      cross-resistance to chlorfenapyr, imidacloprid, emamectin-benzoate, and spinosad,
      but no cross-resistance to acetamiprid and abamectin. The synergists piperonyl
      butoxide (PBO), s, s, s-tributyl phosphorotrithioate (DEF), and triphenyl
      phosphate (TPP) had significant synergism (P < 0.05) on the toxicity of phoxim to
      the resistant (XK), field (BJ), and susceptible (S) populations, while diethyl
      maleate (DEM) had no significant synergism to XK and S populations but had
      significant synergism to BJ population. As compared with S population, the XK and
      BJ populations had significantly increased activities of mixed-functional
      oxidases P450 (2.79-fold and 1.48-fold), b, (2.88-fold and 1.88-fold), O
      demethylase (2.60-fold and 1.68-fold), and carboxylesterase (2.02-fold and 1.61
      fold, respectively), and XK population had a significantly increased
      acetylcholine esterase activity (3.10-fold). Both XK and BJ population had an
      increased activity of glutathione S-transferases (1.11-fold and 1.20-fold,
      respectively), but the increment was not significant. The increased
      detoxification enzymes activities in F. occidentalis could play an important role
      in the resistance of the plant against phoxim.

PMID- 23173471
TI  - [Effects of wheat-oilseed rape intercropping and methyl salicylate application on
      the spatial distributions of Sitobion avenae and its main natural enemies].
AB  - A field investigation was conducted on the spatial distributions of Sitobion
      avenae and its main natural enemies under wheat-oilseed rape intercropping and
      methyl salicylate application. With the development of wheat plant, an
      alternation from aggregation to uniform was observed in the spatial distribution
      of S. avenae under the intercropping and methyl salicylate application, being
      more obvious under the interaction of the two practices. The spatial distribution
      of S. avenae natural enemies was in accordance with that of the aphid. These
      results could be used for the reference of sampling investigation and forecast of
      wheat aphid and its natural enemies in field.

PMID- 23173472
TI  - [Effects of fermented cattle dung on the growth and development of Tenebrio
      molitor larvae].
AB  - In order to make use of and industrialize the animal dung from large cattle
      farms, this paper explored the feasibility of using Tenebrio molitor to digest
      and utilize cattle dung. Cattle dung was mixed with the conventional feed (65%
      wheat bran, 30% corn flour, and 5% bean pulp) of T. molitor in definite
      proportions, and fermented with effective microorganisms (EM). The fermented
      products containing 60% and 80% of cattle dung (FD1 and FD2, respectively) were
      selected to feed T. molitor larvae, and the effects of the fermented products on
      the growth curve, death rate, pupation rate, and antioxidant system of the larvae
      were compared. Compared with CK (conventional deed), the FD1 made the
      developmental duration of the larvae prolonged by 10 days and the larvae's death
      rate upraised somewhat, but made the single larva's total food intake, average
      body mass, crude fat content, and ratio of unsaturated to saturated fat acids
      increased by 49%, 28%, 26%, and 32%, respectively (P < 0.05), and the activity of
      larvae's antioxidant system improved significantly, showing a remarkable
      adaptability of the larvae to FD1. Unlike FD1, FD2 displayed definite
      disadvantages in most test growth indicators, as compared with CK, indicating
      that T. molitor larvae had weak adaptability to FD2. Our findings suggested that
      using FD1 to feed the 3rd instar of T. molitor larvae would have good practical
      prospects in industrializing cattle dung.

PMID- 23173473
TI  - [Effects of soybean trypsinase inhibitor and defense signaling compounds on
      detoxification enzymes in Spodoptera litura (F.) larvae].
AB  - In a long history of interactions between insects and plants, plants have
      developed various anti-insect compounds and defense signaling transduction
      pathways to defend against herbivorous insects, while insects have responded with
      sophisticated detoxification enzyme systems to protect against the toxicity of
      anti-insect compounds. In this study, the 2nd or 3rd instar of Spodoptera litura
      larvae were successively fed with the diets containing 0.5% soybean trypsinase
      inhibitor (SBTI) for six generations to evaluate the effects of SBTI and defense
      signaling compounds on the activities of detoxification enzymes carboxylesterase
      (CarE) and glutathione-S-transferase (GST) in the midgut and fatbody of the
      larvae. After fed with the diets, the CarE and GST activities in the 5th instar
      larvae increased significantly. The CarE activity in the midgut and fatbody of
      the second generation larvae was the highest, being 2.06 and 2.40 times, and 1.96
      and 2.70 times of that of the control, and the GST activity in the midgut and
      fatbody of the fourth and second generations was the highest, being 7.03 and
      11.58 times, and 5.71 and 3.60 times of that of the control, respectively. These
      induced enzyme activities decreased gradually when the larvae continuously grew
      with the SBTI-containing diets. In addition, when the S. litura larvae were pre
      exposed to methyl jasmonate (MeJA) or methyl salicylate (MeSA) for 48 h or fed
      with the diets containing 0.5% SBTI, the activities of CarE and GST in the midgut
      and fatbody increased significantly, and, when the 2nd instar larvae were pre
      exposed to MeJA and MeSA for 48 h, the effects of SBTI on the GST activity in
      larval midgut and fatbody were reduced.

PMID- 23173474
TI  - [Effects of population density and culture volume on the growth and reproduction
      of Moina irrasa].
AB  - A laboratory experiment was conducted to study the effects of different
      population density (D1 : 100 ind x L(-1), D2 : 150 ind x L(-1), D3 : 300 ind x L(
      1)) and culture volume (V1: 50 mL, V2 : 100 mL, V3 : 400 mL) on the growth and
      reproduction of Moina irrasa at 25 degrees C. At the same culture density, the
      body length of the M. irrasa females at their first pregnancy, the first brood,
      and the total offsprings per female decreased with the increase of culture
      volumes, while the sex ratio (male/female) of the offsprings was in adverse. At
      the same culture volumes, the total offsprings per female decreased with the
      increase of culture density. At D1 V1, the body length of the females at their
      first pregnancy (0.95 +/- 0.10 mm) and the total offsprings (171.3 +/- 19.8 ind)
      per female were the maximum. At D3V2, the sex ratio was the maximum (0.54 +/-
      0.05). Culture density, culture volume, and their interactions significantly
      affected the total offsprings per female and the sex ratio (P < 0.001).

PMID- 23173475
TI  - [Cadmium bioaccumulation and its toxicity in Babylonia areolata under different
      nutritional status].
AB  - An indoor exposure experiment with juvenile Babylonia areolata was conducted to
      study its survival, growth, cadmium (Cd) accumulation, metallothionein (MT)
      induction, and glycogen content as well as the DNA integrity of hepatopancreas
      tissue. The juveniles were starved or fed with mussel (Perna viridis) or clamworm
      (Perinereis aibuhitensis), and exposed to 50 microg x L(-1) of Cd2+ for 10 weeks.
      Prolonged starvation and simultaneous exposure to Cd reduced the survival rate of
      B. areolata, and its glycogen was mobilized in great extent. Feeding with P.
      viridis or P. aibuhitensis helped the B. areolata to combat Cd toxicity and
      lessen mortality. After exposed to Cd, the damage of the DNA integrity of
      hepatopancreas tissue for the B. areolata fed with P. viridis or P. aibuhitensis
      could be recovered with time, but not for the starved B. areolata. Prolonged
      starvation caused tissue atrophy and led to Cd accumulation and MT increase,
      while feeding with P. viridis or P. aibuhitensis increased the B. areolata mass
      and lowered the Cd accumulation and MT level because of the tissue dilution
      effect. The B. areolata fed with P. viridis had better growth and lower Cd
      content than that fed with P. aibuhitensis. This study indicated that starvation
      intensified the toxicity of Cd to B. areolata, while prey type had significant
      effects on the growth rate of the B. areolata and indirectly affected its Cd
      accumulation, MT induction, and glycogen consumption. It was suggested that when
      using gastropods such as B. areolata as the indicator species to monitor marine
      environmental pollution, it would be necessary to consider the effects of habitat
      ecological data including food richness and prey type. Moreover, in the high
      density cultivation of B. areolata in factory, rational feeding and periodic
      measurement of Cd concentration in seawater should be made.

PMID- 23173476
TI  - [Construction of suppression subtractive hybridization (SSH) library of copepod
      Pseudodiaptomous annandalei and its ferritin cDNA cloning and differential
      expression under nickel stress].
AB  - To study the molecular response mechanisms of copepod to nickel stress, a
      suppression subtractive hybridization (SSH) cDNA library of Pseudodiaptomous
      annandalei under nickel stress was constructed by using SSH technique, and a
      total of 140 clones were randomly picked from the growing colonies and identified
      by PCR. The recombinant rate of the library was 98.6%, and the volume of the
      library was 1.12 x 10(6) cfu. After the recombinant plasmids were sequenced, a
      partial cDNA fragment of ferritin was recognized based on BLAST searches in NCBI,
      with a size of 859 bp and continuously encoding 170 amino acid residues. The semi
      quantitative PCR results showed that the ferritin cDNA under 24 h nickel stress
      was distinctly up-regulated. The successful construction of the SSH library and
      the obtaining of ferritin cDNA fragment would supply basis for the further study
      of the molecular response mechanisms of copepod to nickel stress.

PMID- 23173477
TI  - [Isolation and identification of aerobic denitrifying bacterium Defluvibacter
      lusatiensis strain DN7 and its heterotrophic nitrification ability].
AB  - An aerobic denitrifying bacterium strain DN7 with excellent nitrate removal
      ability was isolated from the bio-contact oxidation reactor treating bamboo
      process wastewater. The strain had a nitrate removal efficiency of 99.4% in 72 h.
      Cell microscopic observation demonstrated that the strain was a gram-negative
      bacillus with an average size of 0.5 microm x 1.5 microm, and the colony was
      ivory. Based on its biochemical/morphological characteristics and its 16S rDNA
      sequence homologic analysis, this strain was identified as Defluvibacter
      lusatiensis. Its optimal carbon sources were small molecular organic compounds
      such as sodium citrate and glucose, and its nitrogen removal efficiency reached
      99.0% when the medium C/N ratio was 9. The nitrogen removal efficiency could
      reach more than 96% when the nitrate concentration was below 138.48 mg x L(-1)
      and the nitrite concentration was lower than 1.0 mg x L(-1). The strain was not
      sensitive to DO, and the denitrification was favored under neutral or a bit
      alkaline condition. The DN7 also had good ability in degrading ammonim nitrogen,
      with the removal efficiency being 84.7% in 72 h.

PMID- 23173478
TI  - [Phylogenic diversity of soil chemotatic bacteria in a phosphorous-rich area
      around Dianchi Lake of Yunnan Province, Southwest China].
AB  - Phosphate-solubilizing bacteria (PSB) were isolated from 100 soil samples
      collected from a phosphorous-rich area around the Dianchi Lake of Yunnan
      Province, Southwest China. The chemotatic PSB strains were screened by cheA gene
      detection, and their chemotaxis was verified by the method of soft agar plate.
      The tricalcium phosphate (TCP)-solubilizing activities of PSB were determined
      with molybdenum blue spectrophotometry. Based on 16S rRNA sequences, the
      phylogenic relationships of the PSB were analyzed. A total of 145 PSB strains
      with a diameter of phosphate-solubilizing halo zone ranged from 0.5 cm to 2 cm
      were isolated, among which, 37 strains were chemotactic. The 37 chemotactic
      strains showed chemotaxis towards four test attractants, and exhibited TCP
      solubilizing activity. Phylogenic analysis revealed that the 37 chemotatic
      strains were belonged to 17 species of 10 genera, in which, Pseudomonas was
      dominant (9 strains of 5 species), followed by Enterobacter (8 strains of 3
      species). Only one species (Bacillus aryabhattai) was isolated from Bacillus, but
      9 strains were identified.

PMID- 23173479
TI  - [Effects of enhanced UV-B radiation on terrestrial ecosystem carbon cycle: a
      review].
AB  - As one of the most important phenomena of global climate change, the enhancement
      of ultraviolet-B radiation (UV-B, 280-320 nm) could have critical impact on the
      carbon cycle in terrestrial ecosystem. Through the impacts on plant
      photosynthesis, litter decomposition, and soil respiration, the enhanced UV-B
      radiation can affect the carbon input, turnover, and output of terrestrial
      ecosystem. Other climatic factors (ambient CO2 concentration, air temperature,
      and precipitation) may promote or mitigate the impact of enhanced UV-B radiation
      on terrestrial ecosystem carbon cycle. This paper introduced the background of UV
      B radiation enhancement, reviewed the impacts of enhanced UV-B radiation and its
      interactions with other climatic factors on terrestrial ecosystem carbon cycle,
      summarized the existing problems in related researches, and discussed the
      priorities and directions of future researches.

PMID- 23173480
TI  - [Research methods of carbon sequestration by soil aggregates: a review].
AB  - To increase soil organic carbon content is critical for maintaining soil
      fertility and agricultural sustainable development and for mitigating increased
      greenhouse gases and the effects of global climate change. Soil aggregates are
      the main components of soil, and have significant effects on soil physical and
      chemical properties. The physical protection of soil organic carbon by soil
      aggregates is the important mechanism of soil carbon sequestration. This paper
      reviewed the organic carbon sequestration by soil aggregates, and introduced the
      classic and current methods in studying the mechanisms of carbon sequestration by
      soil aggregates. The main problems and further research trends in this study
      field were also discussed.

PMID- 23173481
TI  - [Decision support system for watershed management: a review].
AB  - Watershed management decision support system (DSS) is an intellectual system
      developed for the optimal allocation of water resources by watershed managers,
      and the simulation results of the system can directly affect the scientificity
      and practicability of watershed management. This paper summarized the related
      researches from the aspects of water quantity simulation and deployment systems,
      water quality monitoring and evaluation systems, and integrated watershed
      management systems. The main features and problems in existing DSS were analyzed,
      and the model structure and development status of the representative systems such
      as AQUA-Tool, Elbe-DSS, and HD were introduced. It was suggested that the
      accuracy and stability of simulated results, the succinctness of working process,
      and the high degree of user visualization would be the focuses in developing the
      DSS in the future, and the optimization of program-selecting models and 3D
      visualization tools, the research and development of inter-basin integrated
      management DSS, and the improvement of stakeholder participation would be the
      development trend for the future watershed management DSS.

PMID- 23173482
TI  - [Research advances in anaerobic co-digestion of biogas fermentation substrates].
AB  - With global climate change, more and more attention has been paid to the
      development of bio-energy. Biogas fermentation, as a fairly mature technology of
      bio-matter energy transformation, has received considerable attention and
      experienced much development. How to improve the efficiency of biogas
      fermentation and promote its industrialization is a pressing issue. Anaerobic co
      digestion is a simple, low-cost, and high-efficiency method for enhancing the
      efficiency of biogas fermentation, and received increasing attention from related
      researchers. This paper summarized the characteristics of various fermentation
      substrates, reviewed the research advances in the co-digestion of animal manure,
      sewage sludge, and industrial waste, with the focus on the advantages of co
      digestion and the factors affecting the rate and efficiency of co-digestion, and
      prospected the future research of co-digestion and its application, aimed to
      provide theoretical guidance for the promotion and application of co-digestion
      techniques.

PMID- 23173483
TI  - [Thermophiles and their working mechanisms in degrading excess sludge: a review].
AB  - Activated sludge process is widely used in treating a wide variety of wastewater,
      but the by-product is the large amount of excess sludge. To treat the excess
      sludge properly could spend 25%-60% of the total cost of wastewater treatment,
      while improperly treating the sludge could cause serious secondary pollution.
      Therefore, the reduction of excess sludge is becoming a rising challenge. Using
      thermophiles to degrade excess sludge is a way easy in operation and inexpensive
      in maintenance, being a promising method in application. This paper reviewed the
      recent progress in the researches of sludge-degrading thermophiles, their working
      mechanisms, and the enzymes from thermophiles, such as thermophilic proteolytic
      enzymes and thermophilic lipases which play an important role in the degradation
      of sludge. The factors affecting the degradation of sludge by thermophiles were
      summarized, and the perspectives for the further research on the application of
      thermophiles in digesting sludge were discussed.

PMID- 23173484
TI  - [Membership in the National Order of Nurses is in peril].

PMID- 23173485
TI  - [A nurse who demands the most of oneself, feels benevolence for others, has an
      open spirit and possesses a constant desire to learn].

PMID- 23173486
TI  - [Substance abuse among health personnel, defense or temptation?].
AB  - The increase of the psychological burden at work influences the consumption of
      substances, notably tobacco and alcohol. Healthcare workers are in a high-risk
      sector where we observe increasing malaise. A model of prevention and support
      with the treatment of staff members' addictions has been put in place within the
      Paris public hospital system (AP-HP): the Fides mission.

PMID- 23173487
TI  - [Personal accounts of colleagues suffering from addiction].
AB  - Addictions in the workplace of healthcare professionals remain a taboo subject
      despite their frequency. Talking about the addiction of a colleague is rather
      difficult.

PMID- 23173488
TI  - [Understanding caregivers addiction to alcohol].
AB  - Bringing up the subject of caregivers' addictions in their workplace highlights
      several issues such as denial, a refusal to see, dependency, the approach to take
      and prevention. A reflection on a known but generally hushed up phenomenon.

PMID- 23173489
TI  - [Consumption of psychoactive substances by caregivers].
AB  - Prescribed medication, self-medication or doping the use of psychoactive
      substances by caregivers is varied. Doping behaviour in the care environment is
      under-estimated and trivialised. It is often difficult to spot at an early stage
      and yet this consumption is not without consequences on the quality and safety of
      work. Gerard-Marchant general hospital in Toulouse integrates this issue into its
      professional risk management policy.

PMID- 23173490
TI  - [Treatment program in Spain for nurses suffering from depression and drug
      addiction].
AB  - Since 2000 a programme has existed in Barcelona for nurses suffering from
      depression and addictions. On the basis of voluntary and anonymous admission,
      they can be hospitalised or treated as an outpatient and thereby avoid being
      declared unfit to practise.

PMID- 23173491
TI  - [Prevention of addiction in hospital staff].
AB  - La Pitie-Salpetriere-Charles Foix university hospital group (Paris) has set up a
      task force to help healthcare managers manage a member of staff suffering with
      addiction. An addiction awareness day is also organised, aimed at all staff, with
      information stands and a performance by a theatre company.

PMID- 23173492
TI  - [From the operating room to home care, the same pleasant nursing experience].

PMID- 23173493
TI  - [The gift in caregiving. Is it possible for a gift to be a purely free, no
      strings act?].
AB  - It is not easy to answer this philosophical and moral question. Care situations
      however unfold in a place where the spontaneity of a gift can be expressed in all
      simplicity through the gestures of care.

PMID- 23173494
TI  - [A questioning method to guide the nursing clinical assessment].
AB  - Often minimised by patients, the symptoms they experience in the evolution of
      chronic diseases must be explored rigorously by healthcare professionals. The
      PQRST questioning method is a mnemonic tool which enables the nurse to cover the
      essential elements of the description of a symptom, thereby facilitating the
      clinical assessment.

PMID- 23173495
TI  - [Nursing practice in Lebanon: specificities and challenges].
AB  - The increase in life expectancy as well as the emergence of non-communicable
      diseases have had an influence on the nursing profession in Lebanon. In this
      predominantly female profession, the profession is recognized and encouraged to
      pursue higher education degrees and engage into research. The Order of Nurses in
      Lebanon contributes to the promotion of the professional autonomy of nursing.

PMID- 23173496
TI  - [Dog-assisted intervention with elderly people].
AB  - An experiment to study the benefits of dog-assisted intervention in a long-term
      nursing home was carried out in two care homes in Lyon. It brought together
      trained visiting dogs with their handlers and elderly people. More than a simple
      activity, the experience proved to be therapeutic, soothing and stimulating for
      people who are often withdrawn.

PMID- 23173497
TI  - Antenatal care.

PMID- 23173498
TI  - [Nursing care of the adult patient with generalized epileptic seizure].

PMID- 23173499
TI  - [Type 2 diabetes and diet].

PMID- 23173500
TI  - [Research and student reflexion on the theme of empowerment].

PMID- 23173501
TI  - [Nursing management of catecholamines].

PMID- 23173502
TI  - Are you ready for the next step?

PMID- 23173503
TI  - Leader be nimble.

PMID- 23173504
TI  - Defining leadership: behavioral competencies for success.

PMID- 23173505
TI  - Spanning the gap: strategies that win in turbulent times.

PMID- 23173506
TI  - Four steps to building a successful team.

PMID- 23173507
TI  - Four keys to effective listening.

PMID- 23173508
TI  - The motivated employee.

PMID- 23173509
TI  - The ethics of avoiding nonbeneficial healthcare: unnecessary treatment has both
      financial and moral implications.

PMID- 23173510
TI  - Setting new benchmarks for patient care: quality improvement is a long road, but
      the rewards make the journey worth it.

PMID- 23173511
TI  - Increasing access to care for the underserved: community partnerships can lead to
      real change.

PMID- 23173512
TI  - The challenge of healthcare fraud: supply chain structure could offer ACOs a
      fraud-resistant system.

PMID- 23173513
TI  - Advancing your leadership skillset: succeeding under health reform requires
      flexible leaders.

PMID- 23173515
TI  - Patient-centered leadership: more than a score: focusing on the patient will
      improve both quality and patient satisfaction.

PMID- 23173514
TI  - Three fundamentals of board leadership: focus on job description, committee
      structure and performance is key.

PMID- 23173517
TI  - Close-to-home education: ACHE chapters provide numerous opportunities for local
      professional development.

PMID- 23173516
TI  - Transforming culture to drive cost improvement: senior leaders' role: three
      practices universal among top performers in improving performance.

PMID- 23173518
TI  - The changing landscape of HIV diagnostics.

PMID- 23173520
TI  - "Empty QC": when QC is out of control.

PMID- 23173519
TI  - Risk assessment and quality control: be ready for the new guidance.

PMID- 23173521
TI  - Barcodes: a useful tool for the lab.

PMID- 23173522
TI  - Barcode solutions: it may be time to refresh your laboratory technology.

PMID- 23173523
TI  - Clinical diagnosis of influenza-like illness: the flu and beyond.

PMID- 23173524
TI  - Influenza and RSV: know the diagnostic options.

PMID- 23173525
TI  - The evolution of rapid diagnostic testing in the management of influenza.

PMID- 23173526
TI  - Health information exchange.

PMID- 23173527
TI  - Molecular-based diagnostic testing developments.

PMID- 23173528
TI  - U.S. Congress considers CLIA referral legislation.

PMID- 23173529
TI  - RFID: a medical miracle?

PMID- 23173531
TI  - Medicaid--a moral matter.

PMID- 23173532
TI  - Advocate, enroll: dual strategy for Catholic hospitals.

PMID- 23173533
TI  - The Supreme Court ruling and what it means.

PMID- 23173534
TI  - Systems gear up for new demands.

PMID- 23173535
TI  - Can it succeed? States to roll out more Medicaid managed care.

PMID- 23173536
TI  - Dignity sets strategies to better serve the poor.

PMID- 23173537
TI  - How a Detroit program expands the safety net.

PMID- 23173538
TI  - Dual eligibles: risk shifts to more providers.

PMID- 23173539
TI  - CHE speeds ahead in support of PACE.

PMID- 23173540
TI  - PACE and its future in the new landscape.

PMID- 23173541
TI  - Campaign for action: primary care needs advanced roles for nurses.

PMID- 23173542
TI  - POLST supports care in context of ERDs.

PMID- 23173543
TI  - Social accountability for long-term care organizations: a leadership and mission
      imperative.

PMID- 23173544
TI  - Just because it shocks doesn't make it scandal.

PMID- 23173545
TI  - [Case of chordoid glioma of the third ventricle].

PMID- 23173546
TI  - Thermal annealing induced enhancements of electrical conductivities and mechanism
      for multiwalled carbon nanotubes filled poly(ethylene-co-hexene) composites.
AB  - Thermal annealing-induced enhancements of electrical conductivities at the
      temperature higher than the melting point of poly(ethylene-co-hexene) matrix for
      multiwalled carbon nanotubes filled poly(ethylene-co-hexene) (MWCNTs/PEH)
      composites were investigated by electrical conductivity measurements. Two types
      of MWCNTs with low and high aspect ratios (4 and 31) were added as fillers into
      PEH matrix, respectively for comparison study purpose. The morphological changes
      due to annealing for MWCNTs/PEH composites were observed by SEM. The formation of
      MWCNT networks in the composites were clearly demonstrated by rheological
      measurements. It is surprisingly found that the electrical conductivity for
      MWCNTs/PEH composites with high MWCNT concentrations increases obviously with
      annealing time of 40 min and the maximum increment approaches about 3 orders of
      magnitude with annealing time of 120 min. The increase of electrical conductivity
      of MWCNTs/PEH composites depends on MWCNT content, MWCNT aspect ratio and
      annealing time. SEM results clearly reveal that micrometer-sized MWCNT aggregates
      are broken down and more loosely packed MWCNT networks form due to annealing.
      Different types of networks in the composites are responsible for the evolutions
      of rheological (MWCNT network and PEH chain-MWCNT combined network) and
      electrical conductivity properties (tube-tube contacting MWCNT network). The
      reconstruction of MWCNT network during annealing is attributed to rotational
      diffusion of MWCNTs in PEH matrix at high temperature and the length of MWCNTs
      shows significant effect on this. The obvious enhancements of electrical
      conductivities can be ascribed to the thermal annealing-induced formation of
      loosely packed more homogeneous networks through non-Brownian motions.

PMID- 23173547
TI  - Complete mitogenome of the pale-edged stingray Dasyatis zugei (Myliobatiformes:
      Dasyatidae).
AB  - The complete mitogenome of the pale-edged stingray (Dasyatis zugei) was first
      confirmed in this study. The mitogenome is 18,264 bp in length and contains 13
      protein-coding genes, 2 rRNAs, 22 tRNAs and 1 control region, with the typical
      gene order in vertebrates. Similar to nucleotide composition of most vertebrate
      mitogenomes, the nucleotide composition of the pale-edged stingray demonstrates
      low G and high A+T components. The control region of the pale-edged stingray is
      2523 bp in length, the longest known in Chondrichthyes. The termination
      associated sequence and two short conserved blocks (CSB II and CSB III) are found
      in the control region.

PMID- 23173548
TI  - Language experienced in utero affects vowel perception after birth: a two-country
      study.
AB  - AIMS: To test the hypothesis that exposure to ambient language in the womb alters
      phonetic perception shortly after birth. This two-country study aimed to see
      whether neonates demonstrated prenatal learning by how they responded to vowels
      in a category from their native language and another non-native language,
      regardless of how much postnatal experience the infants had. METHOD: A
      counterbalanced experiment was conducted in Sweden (n = 40) and the USA (n = 40)
      using Swedish and English vowel sounds. The neonates (mean postnatal age = 33 h)
      controlled audio presentation of either native or non-native vowels by sucking on
      a pacifier, with the number of times they sucked their pacifier being used to
      demonstrate what vowel sounds attracted their attention. The vowels were either
      the English/i/or Swedish/y/in the form of a prototype plus 16 variants of the
      prototype. RESULTS: The infants in the native and non-native groups responded
      differently. As predicted, the infants responded to the unfamiliar non-native
      language with higher mean sucks. They also sucked more to the non-native
      prototype. Time since birth (range: 7-75 h) did not affect the outcome.
      CONCLUSION: The ambient language to which foetuses are exposed in the womb starts
      to affect their perception of their native language at a phonetic level. This can
      be measured shortly after birth by differences in responding to familiar vs.
      unfamiliar vowels.

PMID- 23173549
TI  - Xenobiotic receptor humanized mice and their utility.
AB  - The nuclear receptors pregnane X receptor, constitutive androstane receptor, and
      peroxisome proliferator-activated receptor alpha have important endogenous
      functions and are also involved in the induction of drug-metabolizing enzymes and
      transporters in response to exogenous xenobiotics. Though not belonging to the
      same protein family, the Per-Sim-ARNT domain receptor aryl hydrocarbon receptor
      functionally overlaps with the three nuclear receptors in many aspects and is
      therefore included in this review. Significant species differences in ligand
      affinity and biological responses as a result of activation of these receptors
      have been described. Several xenobiotic receptor humanized mice have been created
      to overcome these species differences and to provide in vivo models that are more
      predictive for human responses. This review provides an overview of the different
      xenobiotic receptor humanized mouse models described to date and will summarize
      how these models can be applied in basic research and improve drug discovery and
      development. Some of the key applications in the evaluation of drug induction,
      drug-drug interactions, nongenotoxic carcinogenicity, other toxicity, or efficacy
      studies are described. We also discuss relevant considerations in the
      interpretation of such data and potential future directions for the use of
      xenobiotic receptor humanized mice.

PMID- 23173550
TI  - Ovarian Sertoli-Leydig cell tumor: a report of seven cases and a review of the
      literature.
AB  - The aim of this study was to investigate the clinicopathologic features,
      treatment and outcome of seven patients with an ovarian Sertoli-Leydig cell tumor
      (SLCT). Five patients presented with feminization, two with accompanying
      virilization. One presented with amenorrhea alone. Three of the five patients
      showing feminization symptoms had endocrine-related diseases. Histologically,
      five tumors were well differentiated, the other two were poorly differentiated.
      The latter two patients were misdiagnosed as having an ovarian epithelial
      carcinoma or granulosa cell tumor from frozen sections. Immunohistochemistry
      showed that the tumors were calretinin-positive in two patients and one was
      inhibin-positive. Four patients underwent total abdominal hysterectomy and
      bilateral salpingo-oophorectomy(TAH/BSO) and two were treated by unilateral
      salpingo-oophorectomy. Among them, two patients received adjuvant chemotherapy.
      Six patients were free of disease in a follow-up of 2-34 years and one achieved a
      pregnancy. The remaining patient recurred 4 years later. Feminization as well as
      virilization might provide important clues for a preoperative diagnosis.
      Histological misdiagnosis is probable in poorly differentiated tumors.
      Conservative surgery including retention of fertility can be considered. However,
      the tendency for recurrence in poorly differentiated tumors should be considered.

PMID- 23173551
TI  - Lysozyme as a pH-responsive valve for the controlled release of guest molecules
      from mesoporous silica.
AB  - Mesoporous silica nanoparticles show promise as a drug-carrier vehicle for
      biomedical applications, but the development of simple, biocompatible capping
      systems has remained a challenge. We have found that lysozyme molecules can act
      as a pH-responsive nanovalve to block and unlock the pore entrances of MCM-41
      nanoparticles for guest molecules. Our experiments indicate that pore blocking is
      due to a pH-induced conformational change by which the effective size of the
      protein is changed in a reversible manner. This effect may form the basis of a
      controlled-release system without the need to functionalize the pore mouth and
      caps.

PMID- 23173552
TI  - Drug-conjugated antibodies for the treatment of cancer.
AB  - Despite considerable effort, application of monoclonal antibody technology has
      had only modest success in improving treatment outcomes in patients with solid
      tumours. Enhancing the cancer cell-killing activity of antibodies through
      conjugation to highly potent cytotoxic 'payloads' to create antibody-drug
      conjuates (ADCs) offers a strategy for developing anti-cancer drugs of great
      promise. Early ADCs exhibited side-effect profiles similar to those of
      'classical' chemotherapeutic agents and their performance in clinical trials in
      cancer patients was generally poor. However, the recent clinical development of
      ADCs that have highly potent tubulin-acting agents as their payloads have
      profoundly changed the outlook for ADC technology. Twenty-five such ADCs are in
      clinical development and one, brentuximab vedotin, was approved by the FDA in
      August, 2011, for the treatment of patients with Hodgkin's lymphoma and patients
      with anaplastic large cell lymphoma, based on a high rate of durable responses in
      single arm phase II clinical trials. More recently, a second ADC, trastuzumab
      emtansine, has shown excellent anti-tumour activity with the presentation of
      results of a 991-patient randomized phase III trial in patients with HER2
      positive metastatic breast cancer. Treatment with this ADC (single agent)
      resulted in a significantly improved progression-free survival of 9.6 months
      compared with 6.4 months for lapatinib plus capecitabine in the comparator arm
      and significantly prolonged overall survival. Besides demonstrating excellent
      efficacy, these ADCs were remarkably well tolerated. Thus these, and other ADCs
      in development, promise to achieve the long sought goal of ADC technology, that
      is, of having compounds with high anti-tumour activity at doses where adverse
      effects are generally mild. 

PMID- 23173553
TI  - Cigarette smoke condensate promotes pro-tumourigenic stromal-epithelial
      interactions by suppressing miR-145.
AB  - BACKGROUND: Exposure to factors released from tobacco during chewing or smoking
      is recognized as a major risk factor for oral carcinogenesis and influences the
      phenotype of oral epithelial cells and fibroblasts within the underlying stroma.
      Micro(mi)RNA can regulate the expression of genes within cells, and previous
      studies show that tobacco products can alter the miRNA profiles in lung
      epithelial cells. However, the molecular alterations occurring in oral
      fibroblasts exposed to tobacco constituents remain to be elucidated. METHODS:
      Oral fibroblasts were exposed to cigarette smoke condensate (CSC) and miRNA
      expression compared to untreated controls using tiling low-density arrays (TLDA).
      Expression of miRNA-145 was confirmed by quantitative (q)RT-PCR. The effect of
      CSC on fibroblast cell viability, motility and matrix metalloproteinase (MMP)-2
      expression was measured using MTS, a wound scratch assay and qRT-PCR,
      respectively. Oral cancer cell migration in response to culture supernatants from
      mock, control or pre-miR-145-transfected CSC-treated fibroblasts was analysed by
      chemotaxis assay. RESULTS: TLDA analysis identified widespread changes in the
      miRNA expression profile of fibroblasts exposed to CSC. Pri-, pre- and mature
      miRNA-145 were significantly down-regulated in response to CSC, and this was
      accompanied by up-regulated expression of MMP-2 and increased migration of
      fibroblasts compared to untreated controls. Re-expression of miR-145 abrogated
      the ability of fibroblasts to promote oral cancer cell chemotaxis in response to
      CSC. CONCLUSION: These findings suggest that tobacco constituents influence the
      expression of miRNA within oral fibroblasts promoting a phenotype that increases
      oral cancer migration and sheds new light on the mechanisms underlying oral
      cancer pathogenesis.

PMID- 23173554
TI  - Preclinical evaluation of Gd-DTPA and gadomelitol as contrast agents in DCE-MRI
      of cervical carcinoma interstitial fluid pressure.
AB  - BACKGROUND: High interstitial fluid pressure (IFP) in the primary tumor is
      associated with poor disease-free survival in locally advanced cervical
      carcinoma. A noninvasive assay is needed to identify cervical cancer patients
      with highly elevated tumor IFP because these patients may benefit from
      particularly aggressive treatment. It has been suggested that dynamic contrast
      enhanced magnetic resonance imaging (DCE-MRI) with gadolinium diethylene-triamine
      penta-acetic acid (Gd-DTPA) as contrast agent may provide useful information on
      the IFP of cervical carcinomas. In this preclinical study, we investigated
      whether DCE-MRI with contrast agents with higher molecular weights (MW) than Gd
      DTPA would be superior to Gd-DTPA-based DCE-MRI. METHODS: CK-160 human cervical
      carcinoma xenografts were subjected to DCE-MRI with Gd-DTPA (MW of 0.55 kDa) or
      gadomelitol (MW of 6.5 kDa) as contrast agent before tumor IFP was measured
      invasively with a Millar SPC 320 catheter. The DCE-MRI was carried out at a
      spatial resolution of 0.23 * 0.23 * 2.0 mm3 and a time resolution of 14 s by
      using a 1.5-T whole-body scanner and a slotted tube resonator transceiver coil
      constructed for mice. Parametric images were derived from the DCE-MRI recordings
      by using the Tofts iso-directional transport model and the Patlak uni-directional
      transport model. RESULTS: When gadomelitol was used as contrast agent,
      significant positive correlations were found between the parameters of both
      pharmacokinetic models and tumor IFP. On the other hand, significant correlations
      between DCE-MRI-derived parameters and IFP could not be detected with Gd-DTPA as
      contrast agent. CONCLUSION: Gadomelitol is a superior contrast agent to Gd-DTPA
      in DCE-MRI of the IFP of CK-160 cervical carcinoma xenografts. Clinical studies
      attempting to develop DCE-MRI-based assays of the IFP of cervical carcinomas
      should involve contrast agents with higher MW than Gd-DTPA.

PMID- 23173555
TI  - Percutaneous treatment of a aorto-caval fistula in a old high risk patient.
AB  - BACKGROUND: To remark the feasibility of endovascular treatment of an aorto-caval
      fistula in a old high risk patient with "hostile" abdomen for previous surgeries.
      METHODS: In September 2009 a 81-years-old patient was admitted in emergency at
      our department because of abdominal pain and massive oedema of the lower
      extremities associated to dyspnoea (New York Heart Association (NYHA) functional
      class III). A CT scan showed an aorto-caval fistula involving the abdominal aorta
      below the renal arteries. This abnormal communication was likely due to the
      previous abdominal surgeries, was complicated by occlusion of the inferior vena
      cava at the diaphragm and was responsible for the massive oedema of the lower
      extremities. Because of unstable conditions and hostile abdomen the patient was
      considered unfit for conventional surgery and an endovascular approach was
      planned. After unsuccessful attempt by positioning of an Amplatzer vascular ring
      into the fistula, a Medtronic covered stent-grafts were implanted from the renal
      arteries to the both common iliac arteries. The patient had an impressive
      improvement characterized by a 18 Kg weight loss and a complete restoration of
      the functional capacity (from NYHA class III to NYHA class I) associated to a
      complete resolution of the lower extremities oedema as confirmed at the a month
      CT-scan. CONCLUSION: Endovascular surgery of aorto-caval fistula represents a
      good option in alternative to conventional surgery mostly in old high risk
      patient.

PMID- 23173556
TI  - Chronic HCV infection: epidemiological and clinical relevance.
AB  - Hepatitis C virus (HCV), first recognized as a cause of transfusion-associated
      acute and chronic hepatitis in 1989, plays a major role as a cause of chronic
      liver injury, with potential for neoplastic degeneration. It is mainly
      transmitted by the parenteral route. However, although with lower efficiency, it
      may be also transmitted by sexual intercourses and by the mother-to-child route.
      Epidemiological evidence shows that a wave of infection occurred in the 1945-65
      period (baby boomers) in western countries. After acute infection, as many as 50
      85% of the patients fail to clear the virus resulting in chronic liver infection
      and/or disease. It is estimated that, on a global scale, about 170 million people
      are chronically infected with HCV, leading to about 350.000 deaths yearly. Among
      western countries southern Europe, and particularly Italy, is among the most
      affected areas. The impact on the public health systems is noteworthy, with high
      number of hospitalizations due to chronic liver disease, cirrhosis or
      hepatocellular carcinoma. While waiting for a safe and effective vaccine to be
      made available, new promising direct-acting antiviral (DAA) drugs offer a better
      therapeutic scenario than in the past even for the poor responder genotypes 1 and
      4, provided that effective screening and care is offered. However, the long and
      aspecific prodromic period before clinical symptoms develop is a major obstacle
      to early detection and treatment. Effective screening strategies may target at
      risk groups or age specific groups, as recently recommended by the CDC.

PMID- 23173557
TI  - True blue: S-opsin is widely expressed in different animal species.
AB  - Colour vision in animals is an interesting, fascinating subject. In this study,
      we examined a wide variety of species for expression of S-opsin (blue sensitive)
      and M-/L-opsin (green-red sensitive) in retinal cones using two novel monoclonal
      antibodies specific for peptides from human opsins. Mouse, rat and hare did not
      express one of the investigated epitopes, but we could clearly prove existence of
      cones through peanut agglutinin labelling. Retinas of guinea pig, dog, wolf,
      marten, cat, roe deer, pig and horse were positive for S-opsin, but not for M-/L
      opsin. Nevertheless all these species are clearly at least dichromats, because we
      could detect further S-opsin negative cones by labelling with cone arrestin
      specific antibody. In contrast, pheasant and char had M-/L-opsin positive cones,
      but no S-opsin expressing cones. Sheep, cattle, monkey, men, pigeon, duck and
      chicken were positive for both opsins. Visual acuity analyzed through density of
      retinal ganglion cells revealed least visual discrimination by horses and highest
      resolution in pheasant and pigeon. Most mammals studied are dichromats with
      visual perception similar to red-green blind people. 

PMID- 23173558
TI  - Use of pharmacokinetic modelling to individualize FFP dosing in factor V
      deficiency.
AB  - Therapy with fresh frozen plasma (FFP) confers serious risks, such as contraction
      of blood-borne viruses, allergic reaction, volume overload and development of
      alloantibodies. The aim of this study was to apply principles of pharmacokinetic
      (PK) modelling to individual factor content of FFP to optimize individualized
      dosing, while minimizing potential risks of therapy. We used PK modelling to
      successfully target individual factor replacement in an 8-month-old patient
      receiving FFP for treatment of a severe congenital factor V (FV) deficiency. The
      model fit for the FV activity vs. time data was excellent (r = 0.98) and the
      model accurately predicted FV activity during the intraoperative and
      postoperative period. Accurate PK modelling of individual factor activity in FFP
      has the potential to provide better targeted therapy, enabling clinicians to more
      precisely dose patients requiring coagulation products, while avoiding wasteful
      and expensive product overtreatment, minimizing potentially life-threatening
      complications due to undertreatment and limiting harmful product-associated
      risks.

PMID- 23173559
TI  - A commentary on evidenced-based parenting programs: redressing misconceptions of
      the empirical support for Triple P.
AB  - A meta-analytic review of the Triple P-Positive Parenting program by Wilson et
      al., recently published in BMC Medicine, claimed to demonstrate that although
      Triple P is widely disseminated and adopted, the evidence attesting to the
      effectiveness of the program is not as convincing as it may appear. Although this
      review addresses the important issue of evaluation and reporting methods within
      evidence-based interventions, we contend that the Wilson et al. review contains a
      number of significant conceptual, methodological and interpretational
      inadequacies that render the key conclusions of their review problematic.

PMID- 23173560
TI  - Beyond diversity: how nested predator effects control ecosystem functions.
AB  - The global decline in biodiversity is especially evident in higher trophic levels
      as predators display higher sensitivity to environmental change than organisms
      from lower trophic levels. This is even more alarming given the paucity of
      knowledge about the role of individual predator species in sustaining ecosystem
      functioning. The effect of predator diversity on lower trophic level prey is
      often driven by the increasing chance of including the most influential species.
      Furthermore, intraguild predation can cause trophic cascades with net positive
      effects on basal prey. As a consequence, the effects of losing a predator species
      appear to be idiosyncratic and it becomes unpredictable how the community's net
      effect on lower trophic levels changes when species number is declining. We
      performed a full factorial microcosm experiment with litter layer arthropods to
      measure the effects of predator diversity and context-dependent identity effects
      on a detritivore population and microbial biomass. We show that major parts of
      the observed diversity effect can be assigned to the increasing likelihood of
      including the most influential predator. Further, the presence of a second
      predator feeding on the first predator dampens this dominant effect. Including
      this intraguild predator on top of the first predator is more likely with
      increasing predator diversity as well. Thus, the overall pattern can be explained
      by a second identity effect, which is nested into the first. When losing a
      predator from the community, the response of the lower trophic level is highly
      dependent on the remaining predator species. We mechanistically explain the net
      effects of the predator community on lower trophic levels by nested effects of
      predator identities. These identity effects become predictable when taking the
      species' body masses into account. This provides a new mechanistic perspective
      describing ecosystem functioning as a consequence of species composition and
      yields an understanding beyond simple effects of biodiversity.

PMID- 23173561
TI  - Two novel blood-free solid media for the culture of the salmonid pathogen
      Piscirickettsia salmonis.

PMID- 23173563
TI  - Major postoperative complications and survival for colon cancer elderly patients.
AB  - BACKGROUND: Increased life expectancy has led to elevating the mean age of the
      patients at the time of diagnosis of colon cancer and subsequent treatment.
      Differences in complication rates and outcome between elderly and younger
      patients have been investigated. METHODS: We retrospectively analysed a database
      containing the information of patients who underwent surgery for stage I-III
      colorectal cancer from January 2004 to January 2012 at our institution and
      compared demographic, cancer-related, and outcomes data of 235 elderly patients
      with 211 patients <= 65 years old. RESULTS: Intraoperative complications did not
      differ between young and old patients whereas some differences have been found in
      postoperative and late complications: elderly patients suffered more by ileus (P
      = 0.024), peritonitis or septic shock (P = 0.017), pelvic abscess (P = 0.028),
      wound infection (P = 0.031), and incisional/port herniation (P = 0.012) compared
      with younger patients. Moreover, elderly patients suffered by systemic
      complications such as cardiovascular (4.7% vs. 1.4%, P = 0.049), renal (4.7% vs.
      0.5%, P = 0.006), and respiratory (10.6% vs. 5.2%, P = 0.036). The multivariate
      analysis assessing the odds of having a complication revealed that older age (Odd
      Ratio [OR] 2.75, 95% Confidential Interval [CI]: 1.67-4.52) and open surgery (OR
      1.63, 95% CI: 1.01-2.62) are significantly and independently associated with
      having a complication. CONCLUSIONS: In our series, elderly patients have
      presented a slight higher incidence of comorbidities that may affect the
      incidence rates of postoperative complications. These results have implications
      in increasing the hospital stay as well as a higher rate of death.

PMID- 23173564
TI  - Ulnar-sided pain due to extensor carpi ulnaris tendon subluxation: a case report.
AB  - INTRODUCTION: We present the case of a patient with extensor carpi ulnaris
      tendon subluxation who was first treated for distal radioulnar joint sprain. CASE
      PRESENTATION: A 25-year-old Caucasian man was seen at our policlinic one month
      after he had fallen on his outstretched hand. A diagnosis of extensor carpi
      ulnaris subluxation was made clinically but we also had the magnetic resonance
      imaging scan of the patient's wrist which displayed an increased signal on T2
      weighted images consistent with inflammation around the extensor carpi ulnaris
      tendon. The extensor carpi ulnaris tendon was found to be dislocating during
      supination and relocating during pronation. The sheath was reconstructed using
      extensor retinaculum due to attenuation of subsheath. CONCLUSION: There was no
      recurrent dislocation of the extensor carpi ulnaris tendon of the patient at his
      last follow up 12 months after the operation.

PMID- 23173562
TI  - Downy mildew resistance induced by Trichoderma harzianum T39 in susceptible
      grapevines partially mimics transcriptional changes of resistant genotypes.
AB  - BACKGROUND: Downy mildew, caused by Plasmopara viticola, is one of the most
      severe diseases of grapevine and is commonly controlled by fungicide treatments.
      The beneficial microorganism Trichoderma harzianum T39 (T39) can induce
      resistance to downy mildew, although the molecular events associated with this
      process have not yet been elucidated in grapevine. A next generation RNA
      sequencing (RNA-Seq) approach was used to study global transcriptional changes
      associated with resistance induced by T39 in Vitis vinifera Pinot Noir leaves.
      The long-term aim was to develop strategies to optimize the use of this agent for
      downy mildew control. RESULTS: More than 14.8 million paired-end reads were
      obtained for each biological replicate of T39-treated and control leaf samples
      collected before and 24 h after P. viticola inoculation. RNA-Seq analysis
      resulted in the identification of 7,024 differentially expressed genes,
      highlighting the complex transcriptional reprogramming of grapevine leaves during
      resistance induction and in response to pathogen inoculation. Our data show that
      T39 has a dual effect: it directly modulates genes related to the microbial
      recognition machinery, and it enhances the expression of defence-related
      processes after pathogen inoculation. Whereas several genes were commonly
      affected by P. viticola in control and T39-treated plants, opposing modulation of
      genes related to responses to stress and protein metabolism was found. T39
      induced resistance partially inhibited some disease-related processes and
      specifically activated defence responses after P. viticola inoculation, causing a
      significant reduction of downy mildew symptoms. CONCLUSIONS: The global
      transcriptional analysis revealed that defence processes known to be implicated
      in the reaction of resistant genotypes to downy mildew were partially activated
      by T39-induced resistance in susceptible grapevines. Genes identified in this
      work are an important source of markers for selecting novel resistance inducers
      and for the analysis of environmental conditions that might affect induced
      resistance mechanisms.

PMID- 23173565
TI  - Are keloid and hypertrophic scar different forms of the same disorder? A
      fibroproliferative skin disorder hypothesis based on keloid findings.
AB  - Hypertrophic scars (HSs) and keloids are commonly seen as two different diseases
      by both clinicians and pathologists. However, as supported by histological
      evidence showing they share increased numbers of fibroblasts and accumulate
      collagen products, HS and keloid might be different forms of the same
      pathological entity, rather than separate conditions. To test this hypothesis,
      keloids from patients who underwent scar excisions (n = 20) in Nippon Medical
      School from 2005 to 2010 were examined histologically. The proportion and
      distribution of cellular and matrix collagen components were evaluated at the
      centre and periphery of each sample. In keloid samples, coexistence of hyalinised
      collagen, which is the most important pathognomonic characteristic of a keloid
      and dermal nodules that are considered to be characteristic of HS, was found.
      Moreover, hyalinised fibres appeared to initiate from the corner of the dermal
      nodules. Key features of inflammation such as microvessels, fibroblasts and
      inflammatory cells all decreased gradually from the periphery to the centre of
      keloids, indicative of reduced inflammation in the centre. Thus, we hypothesise
      that HS and keloid can be considered as successive stages of the same
      fibroproliferative skin disorder, with differing degrees of inflammation that
      might be affected by genetic predisposition. 

PMID- 23173566
TI  - Fine-scale environmental control of hybridization in oaks.
AB  - Natural hybridization is attracting much interest in modern speciation and
      conservation biology studies, but the underlying mechanisms remain poorly
      understood. In particular, it is unclear why environmental changes often increase
      hybridization rates. To study this question, we surveyed mating events in a mixed
      oak stand and developed a spatially explicit individual-based hybridization
      model. This model, where hybridization is frequency-dependent, pollen is
      nonlimiting and which allows immigrant pollen to compete with local pollen, takes
      into account species-specific pollen dispersal and sexual barriers to
      hybridization. The consequences of pollen limitation on hybridization were
      studied using another simple model. The results indicate that environmental
      changes could increase hybridization rates through two distinct mechanisms.
      First, by disrupting the spatial organization of communities, they should
      decrease the proportion of conspecific pollen available for mating, thus
      increasing hybridization rates. Second, by decreasing the density of
      conspecifics, they should increase pollen limitation and thus hybridization
      rates, as a consequence of chance pollination predominating over deterministic
      pollen competition. Altogether, our results point to a need for considering
      hybridization events at the appropriate level of organization and provide new
      insights into why hybridization rates generally increase in disturbed
      environments.

PMID- 23173567
TI  - The burden of influenza complications in different high-risk groups: a targeted
      literature review.
AB  - OBJECTIVES: The objective was to review the published literature on seasonal
      influenza to assess the differences between complications and mortality rates for
      those adults at high risk of influenza complications, including the resource use
      of those hospitalized with influenza complications. METHODS: A targeted
      literature review was performed using electronic database keyword searches,
      specific inclusion criteria, quality rating of the reviewed full-text articles
      and abstraction of data to present published evidence on the incidence,
      complication rates and health service use associated with clinical influenza in
      different adult high-risk groups including those who are aged 65 years and older
      or those with different chronic underlying medical conditions. RESULTS: Key
      findings for incidence rates of clinical influenza were that incidence rates are
      similar among people with chronic cardiovascular or respiratory comorbidity, and
      may be higher in those with allogeneic stem cell transplants compared to those
      with autologous transplants. Rates of hospitalization and/or pneumonia or lower
      respiratory tract infection for those with chronic conditions or those who are
      immunocompromised are substantially higher than those in people over age 65 but
      without additional high-risk factors. A person who is hospitalized and has a
      laboratory-confirmed influenza diagnosis has a probability of intensive care unit
      admission of between 11.8-28.6% and of death of between 2.9-14.3%. CONCLUSIONS:
      These findings indicate that although the burden of influenza varied across high
      risk groups, it also varied widely across studies within a single high-risk
      group. A key finding was that those over 65 years of age but without additional
      high-risk factors had a low risk of influenza complications. A limitation of the
      review is that most of the studies of hospitalized patients did not present
      outcomes data separately by high-risk group and only limited data were identified
      on rates of hospitalization or lower respiratory tract infection for most high
      risk groups. Information about influenza complication rates and resource use,
      including influenza vaccines, chemoprophylaxis and/or treatment strategies for
      different high-risk groups, is needed to evaluate new interventions.

PMID- 23173568
TI  - Inhibition of breast cancer cell proliferation in repeated and non-repeated
      treatment with zoledronic acid.
AB  - BACKGROUND: Zoledronic acid is used to treat bone metastases and has been shown
      to reduce skeletal-related events and exert antitumor activity. The present in
      vitro study investigates the mechanism of action of Zoledronic Acid on breast
      cancer cell lines with different hormonal and HER2 patterns. Furthermore, we
      investigated the efficacy of repeated versus non-repeated treatments. METHODS:
      The study was performed on 4 breast cancer cell lines (BRC-230, SkBr3, MCF-7 and
      MDA-MB-231). Non-repeated treatment (single exposure of 168 hrs' duration) with
      zoledronic acid was compared with repeated treatment (separate exposures, each of
      48 hrs' duration, for a total of 168 hrs) at different dosages. A dose-response
      profile was generated using sulforhodamine B assay. Apoptosis was evaluated by
      TUNEL assay and biomolecular characteristics were analyzed by western blot.
      RESULTS: Zoledronic acid produced a dose-dependent inhibition of proliferation in
      all cell lines. Anti-proliferative activity was enhanced with the repeated
      treatment, proving to be statistically significant in the triple-negative lines.
      In these lines repeated treatment showed a cytocidal effect, with apoptotic cell
      death caused by caspase 3, 8 and 9 activation and decreased RAS and pMAPK
      expression. Apoptosis was not observed in estrogen receptor-positive line: p21
      overexpression suggested a slowing down of cell cycle. A decrease in RAS and
      pMAPK expression was seen in HER2-overexpressing line after treatment.
      CONCLUSIONS: The study suggests that zoledronic acid has an antitumor activity in
      breast cancer cell lines. Its mechanism of action involves the decrease of RAS
      and RHO, as in osteoclasts. Repeated treatment enhances antitumor activity
      compared to non-repeated treatment. Repeated treatment has a killing effect on
      triple-negative lines due to apoptosis activation. Further research is warranted
      especially in the treatment of triple-negative breast cancer.

PMID- 23173569
TI  - Identification of the HDL-ApoCIII to VLDL-ApoCIII ratio as a predictor of
      coronary artery disease in the general population: the Chin-Shan Community
      Cardiovascular Cohort (CCCC) study in Taiwan.
AB  - BACKGROUND: Apolipoprotein (Apo) levels are considered more reliable than plasma
      lipoprotein levels for predicting coronary artery disease (CAD). However, a
      unanimous Apo marker for CAD has not been identified. In the Chin-Shan Community
      Cardiovascular Cohort (CCCC), we sought to identify a common Apo marker for
      predicting CAD in the general population. METHODS: We examined the cross
      sectional association between Apo markers and CAD in the CCCC from 1990 to 2001.
      Among 3,602 subjects, 90 had angiographically proven CAD (>50% stenosis in >=1
      vessel), and 200 did not have CAD. These subjects were divided into the following
      4 groups for analysis: normolipidemic (total cholesterol [TC] <200 mg/dL,
      triglyceride [TG] <150 mg/dL), hypertriglyceridemic (TC <200 mg/dL, TG >=150
      mg/dL), hypercholesterolemic (TC >=200 mg/dL, TG <150 mg/dL), and hyperlipidemic
      (TC >=200 mg/dL, TG >=150 mg/dL). RESULTS: Compatible with findings in other
      populations, our results showed that CAD patients in the CCCC had higher ApoB and
      lower high-density lipoprotein (HDL) cholesterol and ApoAI concentrations than
      non-CAD subjects, but the differences were not significant in all groups. Plasma
      concentrations of ApoE and lipoprotein (a) were not consistently correlated with
      CAD. In contrast, the ratio of HDL-ApoCIII to very-low-density lipoprotein (VLDL)
      ApoCIII was the only universal determinant for CAD in the normolipidemic group
      (P=0.0018), the hypertriglyceridemic group (P=0.0001), the hypercholesterolemic
      group (P=0.0001), and the hyperlipidemic group (P=0.0001). Overall, a high HDL
      ApoCIII/VLDL-ApoCIII ratio was observed in all CAD patients, including those with
      a normal lipid profile. In multivariate analyses, the HDL-ApoCIII/VLDL-ApoCIII
      ratio was the strongest predictor for CAD among all lipid factors investigated
      (odds ratio, 2.04; 95% confidence interval, 1.46-2.84; P<0.0001). CONCLUSIONS: A
      high HDL-ApoCIII to VLDL-ApoCIII ratio is a better marker for predicting CAD than
      are the conventional lipid markers or ApoAI and ApoB. High HDL-ApoCIII and low
      VLDL-ApoCIII values in CAD, irrespective of lipid variations, suggest that
      ApoCIII is markedly transported from VLDL to HDL in this disease. Measurement of
      plasma ApoCIII may improve CAD prediction in the general population.

PMID- 23173570
TI  - Coadministration of tacrolimus with corticosteroid accelerates recovery in
      refractory patients with polymyositis/ dermatomyositis: a retrospective study.
AB  - BACKGROUND: To investigate whether or not coadministration of tacrolimus (TAC)
      with prednisolone (PSL) can produce a beneficial effect in the treatment of
      polymyositis/ dermatomyositis (PM/DM). METHODS: We reviewed medical records of 32
      PM/DM patients who had been admitted to our hospital, and abstracted those who
      had received TAC in addition to oral PSL for treatment. The clinical usefulness
      of TAC in PM/DM was objectively evaluated focusing upon the manual muscle
      strength test (MMT) score, serum creatine kinase (CK) and tapering of PSL.
      RESULTS: Nine patients with PM and 6 with DM were enrolled in this study. TAC was
      added because of difficulty in reduction of PSL in 12 patients and recurrence
      with corticosteroid-induced complications in the remaining 3. Both PM and DM
      patients showed significant increases in the MMT score and significant decreases
      in serum CK 1 to 3 months after starting TAC compared with before. Skin symptoms
      in a clinically amyopathic DM patient also improved 1 month after starting TAC.
      The daily dosage of PSL could be significantly reduced in both PM and DM after
      starting TAC compared with before. No serious adverse events ascribable to TAC
      occurred in any patients. CONCLUSION: Additional use of TAC with PSL may safely
      promote improvement of PM/DM and also accelerate tapering of the latter.

PMID- 23173572
TI  - Comparing health-related quality of life of employed women and housewives: a
      cross sectional study from southeast Iran.
AB  - BACKGROUND: Quality of life differs for different people in different situations
      and is related to one's self-satisfaction with life. Considering the role of
      women in family and social health and the specific cultural characteristics of
      our province, we aimed to compare the quality of life of employed women with
      housewives in Zahedan, Iran. METHODS: This cross-sectional study was carried out
      during 2009-2010 in Zahedan, Iran. The sample consisted of 110 housewives and 110
      employed women selected randomly from ten health care centers. Health-related
      quality of life was assessed using the SF-36. Analysis of covariance (ANCOVA) was
      used to compare quality of life in housewives and employed women while
      controlling for age, education and income. RESULTS: The mean (+/-SD) age of
      participants was 33.87+/- 8.95 years. Eighty-eight women (40%) had a university
      degree with a mean (+/-SD) official education of 10.8 (+/-4.9) years. The results
      indicated that employed women scored higher than housewives in all measures
      except for physical functioning. The differences were found to be remarkable for
      vitality, mental health and role emotional. However, after controlling for age,
      education and family income, none of differences reached significant level.
      CONCLUSION: After controlling for potential confounders, the findings from this
      study indicated that there were no significant differences in quality of life
      between employed women and housewives. However, employed women scored higher on
      the SF-36, especially on the role emotional, vitality, and mental health. The
      findings suggest that associations exist between some aspects of health-related
      quality of life and employment. Indeed improving health-related quality of life
      among housewives seems essential.

PMID- 23173571
TI  - Replication of somatic micronuclei in bovine enucleated oocytes.
AB  - BACKGROUND: Microcell-mediated chromosome transfer (MMCT) was developed to
      introduce a low number of chromosomes into a host cell. We have designed a novel
      technique combining part of MMCT with somatic cell nuclear transfer, which
      consists of injecting a somatic micronucleus into an enucleated oocyte, and
      inducing its cellular machinery to replicate such micronucleus. It would allow
      the isolation and manipulation of a single or a low number of somatic
      chromosomes. METHODS: Micronuclei from adult bovine fibroblasts were produced by
      incubation in 0.05 MUg/ml demecolcine for 46 h followed by 2 mg/ml mitomycin for
      2 h. Cells were finally treated with 10 MUg/ml cytochalasin B for 1 h. In vitro
      matured bovine oocytes were mechanically enucleated and intracytoplasmatically
      injected with one somatic micronucleus, which had been previously exposed
      [Micronucleus- injected (+)] or not [Micronucleus- injected (-)] to a transgene
      (50 ng/MUl pCX-EGFP) during 5 min. Enucleated oocytes [Enucleated (+)] and
      parthenogenetic [Parthenogenetic (+)] controls were injected into the cytoplasm
      with less than 10 pl of PVP containing 50 ng/MUl pCX-EGFP. A non-injected
      parthenogenetic control [Parthenogenetic (-)] was also included. Two hours after
      injection, oocytes and reconstituted embryos were activated by incubation in 5
      MUM ionomycin for 4 min + 1.9 mM 6-DMAP for 3 h. Cleavage stage and egfp
      expression were evaluated. DNA replication was confirmed by DAPI staining. On day
      2, Micronucleus- injected (-), Parthenogenetic (-) and in vitro fertilized (IVF)
      embryos were karyotyped. Differences among treatments were determined by Fisher's
      exact test (p<=0.05). RESULTS: All the experimental groups underwent the first
      cell divisions. Interestingly, a low number of Micronucleus-injected embryos
      showed egfp expression. DAPI staining confirmed replication of micronuclei in
      most of the evaluated embryos. Karyotype analysis revealed that all Micronucleus
      injected embryos had fewer than 15 chromosomes per blastomere (from 1 to 13),
      while none of the IVF and Parthenogenetic controls showed less than 30
      chromosomes per spread. CONCLUSIONS: We have developed a new method to replicate
      somatic micronuclei, by using the replication machinery of the oocyte. This could
      be a useful tool for making chromosome transfer, which could be previously
      targeted for transgenesis.

PMID- 23173573
TI  - Generalised pollination systems for three invasive milkweeds in Australia.
AB  - Because most plants require pollinator visits for seed production, the ability of
      an introduced plant species to establish pollinator relationships in a new
      ecosystem may have a central role in determining its success or failure as an
      invader. We investigated the pollination ecology of three milkweed species -
      Asclepias curassavica, Gomphocarpus fruticosus and G. physocarpus - in their
      invaded range in southeast Queensland, Australia. The complex floral morphology
      of milkweeds has often been interpreted as a general trend towards specialised
      pollination requirements. Based on this interpretation, invasion by milkweeds
      contradicts the expectation than plant species with specialised pollination
      systems are less likely to become invasive that those with more generalised
      pollination requirements. However, observations of flower visitors in natural
      populations of the three study species revealed that their pollination systems
      are essentially specialised at the taxonomic level of the order, but generalised
      at the species level. Specifically, pollinators of the two Gomphocarpus species
      included various species of Hymenoptera (particularly vespid wasps), while
      pollinators of A. curassavica were primarily Lepidoptera (particularly nymphalid
      butterflies). Pollinators of all three species are rewarded with copious amounts
      of highly concentrated nectar. It is likely that successful invasion by these
      three milkweed species is attributable, at least in part, to their generalised
      pollinator requirements. The results of this study are discussed in terms of how
      data from the native range may be useful in predicting pollination success of
      species in a new environment.

PMID- 23173574
TI  - Apoptotic and anti-angiogenic effects of benzimidazole compounds: relationship
      with oxidative stress mediated ischemia/reperfusion injury in rat hind limb.
AB  - Ischemia/reperfusion (I/R)-induced injury is a pathophysiological process
      consisting of a complex cascade characterized by an increase in reactive oxygen
      species production, pro-inflammatory cytokine release, and activated endothelial
      cells leading to cell damage and death. The aim of this study was to investigate
      effects of substituted 2-benzylbenzimidazole derivatives, 2-(3
      methoxybenzyl)benzimidazole (BB3) and 2-(4-methoxybenzyl)benzimidazole (BB4), on
      I/R-induced changes in the markers of oxidative stress, apoptosis, and
      angiogenesis in rats. BB3 and BB4 were synthesized with microwave irradiation and
      conventional Phillips methods. I/R was performed by occlusion of femoral artery.
      Catalase activity and reduced glutathione (GSH) levels as well as caspase-3, -8,
      and -9 activities were measured in muscle tissues as an index for oxidative
      stress and apoptosis, respectively. Vascular endothelial growth factor (VEGF)
      levels as an index for angiogenesis were also measured in the muscle tissues and
      sera. I/R decreased GSH levels, increased catalase activity and VEGF levels, and
      did not change caspase-3, -8, and -9 activities compared to control groups. BB3
      and BB4 caused a further decrease in GSH levels and increased caspase-3, -8, and 
      9 activities in I/R group. These compounds caused a further increase in catalase
      activity and prevented the increase in VEGF levels induced by I/R. These data
      suggest that BB3 and BB4 exhibit apoptotic and anti-angiogenic activity with pro
      oxidative effects resulting in oxidative stress in pathophysiological process of
      I/R-induced hind limb injury in rats.

PMID- 23173575
TI  - Efficacy and safety of H1-antihistamines: an update.
AB  - H1-antihistamines are inverse agonists that combine with and stabilize inactive
      conformation of H1-receptors. Thus they interfere with actions of histamine at H1
      receptors. They are widely used for treatment of allergic rhinitis, allergic
      conjunctivitis, urticaria, coughs, colds and insomnia. H1-antihistamines are
      classified as older 'first generation' and newer 'second generation'. First
      generation H1-antihistamines have poor receptor H1-receptor selectivity, and
      cross blood-brain-barrier. They have a lot of adverse events such as anti
      muscarinic, anti-alpha-adrenergic, anti-serotonin, and sedative effects. In
      contrast, second generation H1-antihistamines were highly selective for the
      histamine H1-receptor, do not cross the blood brain barrier, and have minimal
      adverse events. The risks of first-generation H1-antihistamines have been clearly
      underestimated, particularly when purchased as nonprescribed over the counter
      medications by public. This review summarizes current literature to evaluate
      antihistamines including their mechanism, indications and side-effects.

PMID- 23173576
TI  - Increased production of nitric oxide mediates selective organ-specific effects of
      endotoxin on oxidative stress.
AB  - Endotoxemic shock is a systemic inflammatory response that is associated with
      increased nitric oxide (NO) production by inducible NO synthase (iNOS) which
      contributes to hypotension, vascular hyporeactivity, and multiple organ failure.
      Oxidative stress (OS) is a major contributing factor to high morbidity and
      mortality in endotoxemic shock. We have previously demonstrated that endotoxin
      induced fall in blood pressure is associated with an increase in nitrite levels
      in serum, kidney, heart, thoracic aorta (TA), and superior mesenteric artery
      (SMA), a decrease in malondialdehyde (MDA) levels in the kidney, heart, TA, and
      SMA, and an increase in myeloperoxidase (MPO) activity in the heart and TA, but a
      decrease in the kidney and SMA of rats. In this study, we further investigated
      whether increased production of iNOS-derived NO contributes to endotoxin induced
      changes in the biomarkers of OS in the liver, lungs, brain, spleen, and femoral
      artery (FA) of rats. Endotoxin-induced increase in nitrite production was
      associated with a decrease in reduced glutathione levels in the liver, lungs,
      brain, spleen, and FA. MPO activity was increased by endotoxin in the lungs,
      spleen, and FA, but decreased in the liver and brain. MDA levels were increased
      by endotoxin in the lungs, brain, spleen, and FA, but were decreased in the
      liver. Activities of superoxide dismutase and catalase were decreased in the
      liver and spleen, but were increased in the lungs, brain, and FA. These effects
      of endotoxin were prevented by a selective iNOS inhibitor, phenylene-1,3
      bis[ethane-2-isothiourea] dihydrobromide. These data suggest that iNOS-derived NO
      mediates selective organ-specific effects of endotoxin on OS.

PMID- 23173577
TI  - A multigenic combination of estrogen related genes are associated with the
      duration of fertility period in the Spanish population.
AB  - OBJECTIVE: The duration of the fertile period (FP) can be considered a complex
      parameter that depends on the interaction of multiple factors. In the present
      study, the role of interaction between genetic variants within estrogen synthesis
      and signaling pathways in the FP in Spanish women is studied. MATERIAL AND
      METHODS: Nine single nucleotide polymorphisms (SNPs) located at different
      candidate genes related to the estrogen signaling pathway were analyzed in 1980
      Spanish postmenopausal women. RESULTS: Independently, none of the nine markers
      were significantly associated with age at menopause. In contrast, survival
      analysis techniques suggest several epistatic interactions including these
      markers in relation to age at menopause, especially between ESR2, NRIP1 and
      BMP15: women who showed the three markers ESR2 (AA), BMP15 (rs3897937) (TC) and
      NRIP1 (AA), the FP was shorter than the control group of women without any of
      these markers (32.36 +/- 1.49 versus 34.94 +/- 0.32 years; p = 0.026). The
      digenic BMP15 (rs3897937) (TC) and NRIP1 (AA) combination were also associated
      with a decreased duration of the FP (33.32 +/- 0.96 years, p = 0.031).
      CONCLUSIONS: The results suggest that interactions of estrogen-related alleles
      may contribute to variance in FP in Spanish women.

PMID- 23173578
TI  - Fibroblast growth factor-21 is a promising dietary restriction mimetic.
AB  - Dietary or caloric restriction (DR or CR), typically a 30%-40% reduction in ad
      libitum or "normal" nutritional energy levels, has been reported to extend life
      span and health span in diverse organisms, including mammals. Although the life
      span benefit of DR in primates and humans is unproven, preliminary evidence
      suggests that DR confers health span benefits. A serious effort is underway to
      discover or engineer DR mimetics. The most straightforward path to a DR mimetic
      requires a detailed understanding of the molecular mechanisms that underlie DR
      and related life span-enhancing protocols. Increased expression of fibroblast
      growth factor-21 (FGF21), a putative mammalian starvation master regulator,
      promotes many of the same beneficial physiological changes seen in DR animals,
      including decreased glucose levels, increased insulin sensitivity, and improved
      fatty acid/lipid profiles. Ectopic over-expression of FGF21 in transgenic mice
      (FGF21-Tg) extends life span to a similar extent as DR in a recent study. FGF21
      may achieve these effects by attenuating growth hormone (GH)/insulin-like growth
      factor-1 (IGF1) signaling. Although FGF21 expression does not increase during DR,
      and therefore is unlikely to mediate DR, it does increase during short-term
      starvation in rodents, which is a critical component of alternate day fasting, a
      DR-like protocol that also increases life span and health span in mammals.
      Various drugs have been reported to induce FGF21, including peroxisome
      proliferator-activated receptor-alpha (PPARalpha) agonists such as fenofibrate,
      the histone deacetylase inhibitor sodium butyrate, and adenosine monophosphate
      (AMP) kinase activators metformin and 5-amino-1-beta-D-ribofuranosyl-imidazole-4
      carboxamide (AICAR). Of these, only metformin has been reported to extend life
      span in mammals, and the extent of benefit is less than that seen with ectopic
      FGF21 expression. Perhaps the most parsimonious explanation is that high,
      possibly un-physiological, levels of FGF21 are needed to achieve maximum life
      span and health span benefits and that sufficiently high levels are not achieved
      by the identified FGF21 inducers. More in-depth studies of the effects of FGF21
      and its inducers on longevity and health span are warranted.

PMID- 23173579
TI  - Nanoparticle mediated brain targeted delivery of gallic acid: in vivo behavioral
      and biochemical studies for improved antioxidant and antidepressant-like
      activity.
AB  - CONTEXT: Gallic acid had been reported to possess antidepressant like activity,
      which may be attributed to its CNS effects like increase in reduced glutathione
      levels, increased catalase activity and decreased malonaldehyde levels in brain.
      OBJECTIVE: This study was designed to enhance the antidepressant-like activity of
      gallic acid (GA) using nanoparticulate delivery system in swiss male albino mice
      and to explore the possible underlying mechanisms for this activity. METHODS: GA
      loaded chitosan nanoparticles (GANP) and corresponding tween 80 coated batch
      (cGANP) were formulated for brain targeting of GA and characterized for
      physicochemical parameters, morphology, differential scanning calorimetry and in
      vitro drug release. GA, GANP, cGANP (dose equivalent to GA 10 mg/kg, i.p.) and
      positive control drug, Fluoxetine (10 mg/kg, i.p.) were administered for
      successive seven days to male swiss albino mice. Then, the in vivo antidepressant
      like activity was evaluated using Despair Swim Test (DST) and Tail Suspension
      Test (TST); along with the evaluation of MAO-A activity, reduced glutathione,
      malonaldehyde level, catalase and locomotor activity in mice. KEYFINDINGS: cGANP
      (equivalent to 10 mg/kg, i.p.) significantly decreased immobility period of mice
      in DST and TST, indicating significant antidepressant-like activity. There was no
      significant effect on locomotor activity of the mice by GA and its nanoparticle
      formulations. cGANP (10 mg/kg, i.p.) significantly decreased Monoamine oxidase-A
      (MAO-A) activity, malondialdehyde levels, and catalase activity in mice.
      CONCLUSIONS: GA possess significant antidepressant like activity and ligand
      coated nanoparticle approach with improved brain targeting may serve as an
      effective approach to enhance such effect.

PMID- 23173580
TI  - Strategies to deliver microRNAs as potential therapeutics in the treatment of
      cardiovascular pathology.
AB  - CONTEXT: MicroRNAs (miRNAs) are important and powerful mediators in a variety of
      diseases including cardiovascular pathology. Thus, they emerged as interesting
      new drug targets. However, it is important to develop efficient transfer tools to
      successfully deliver miRNAs or antisense oligonucleotides (antagomirs) to the
      target tissue. OBJECTIVE: The aim of this study was to review the scientific
      literature on delivery techniques currently used for transfer of miRNAs and
      antagomirs to animal models of cardiovascular disease and those that are likely
      to be used for therapeutic miRNA transport in the nearest future. METHODS: The
      research was carried out by consulting the following medical websites: Medicus
      Medline Index, PubMed (National Library of Medicine), and a registry database of
      clinical trials conducted in USA ( www.clinicaltrials.gov). The selection gathers
      articles written in English, published from January 2012. RESULTS: A current
      delivery technique includes chemical modification of antagomirs with 2-O-methyl
      group or 2-O-methyoxyethyl or using locked nucleic acids to increase drug
      stability and affinity. Development of miRNA sponges/decoys aims to target all
      members of a miRNA seed family of interest. A further strategy to augment miRNA
      levels is to use miRNA delivery through viral-based vectors including
      adenoviruses, adeno-associated viruses, and lentiviruses. To date, a variety of
      nanocarriers is available for efficient delivery of miRNAs. Microvesicles, and
      apoptotic bodies that contain circulating miRNAs could be also used as
      therapeutic transport systems in the nearest future. CONCLUSION: Development of
      new miRNA carrier systems with advanced properties and large animal data in the
      cardiovascular field is highly recommended.

PMID- 23173581
TI  - Characterization of the minimal replicon of pHM300 and independent copy number
      control of major and minor chromosomes of Haloferax mediterranei.
AB  - The presence of minichromosomes is very common in haloarchaea, but little is
      known about the coordination of replication between the major and minor
      chromosomes. In this study, we analyzed the replication of pHM300, a 321,908-bp
      minichromosome, which encodes versatile metabolism pathways in Haloferax
      mediterranei. The replication origin of pHM300 was predicted in the 699-bp
      intergenic region between the cdc6K and tbp4 gene, and the minimal replicon,
      consisting of an AT-rich region flanked by putative origin recognition boxes
      (ORBs) and the adjacent cdc6K gene, was determined by assaying for its ability to
      replicate autonomously in Haloarcula hispanica. Southern blot analysis indicated
      that the ratio of pHM300 to chromosome increased from the early exponential to
      middle stationary phase. The copy numbers of these minor and major chromosomes
      were then evaluated by real-time PCR and showed that both decreased in stationary
      phase. However, the decrease in the copy number of the major chromosome was a
      little earlier and much greater than that of pHM300, revealing that the copy
      number control of the minichromosome pHM300 is independent from that of the major
      chromosome in H. mediterranei.

PMID- 23173582
TI  - Pharmacological properties of glutamatergic drugs targeting NMDA receptors and
      their application in major depression.
AB  - BACKGROUND: A growing body of evidence suggests that glutamatergic system,
      especially the abnormalities of glutamate and N-methyl-D-aspartate (NMDA)
      receptors contribute to the pathophysiology of major depressive disorders. An
      imbalance in glutamatergic neurotransmission may contribute to increased levels
      of NMDA agonism, thereby enhancing excitatory activity in most brain circuits
      involved in major depression. Although NMDA receptor antagonists have been
      demonstrated to possess antidepressant-like activity, the molecular changes
      underlying abnormal glutamatergic signaling still remain poorly understood.
      Therefore, we aimed to review the current literature focusing on the main
      pharmacological properties and the impact of glutamatergic drugs targeting NMDA
      receptors in major depression. METHODS: A detailed literature search in
      PubMed/Medline and ScienceDirect databases using the terms glutamate, depression
      and major depressive disorder has been performed. RESULTS: Most drugs acting at
      glutamatergic receptors showed biochemical effects indicative of antidepressant
      activity in both clinical and preclinical studies. Recent neuroimaging and
      genetic contributions also confirm the antidepressant properties of these
      medications. However, human studies including NMDA receptor antagonists provided
      mixed results. In overall, glutamatergic receptor modulation may facilitate
      neuronal stem cell enhancement (neurogenesis) as well as the release of
      neurotransmitters associated with treatment response to depression in humans.
      LIMITATIONS: Cognitive side effects and psychotomimetic properties complicate the
      application and the development of clinically useful agents. CONCLUSIONS:
      Glutamatergic system represents a target for effective intervention in major
      depression. Specifically, those glutamatergic medications targeting NMDA
      receptors by inhibiting the release of neurotransmitters or modulating its post
      synaptic responses may serve as molecule modulators with specific antidepressant
      properties.

PMID- 23173583
TI  - Molecular markers of cardiovascular damage in hypertension.
AB  - There is increasing evidence that an elevation of oxidative stress and associated
      oxidative damages are mediators of vascular injury in various cardiovascular
      pathologies, including hypertension. Accumulation of oxidative damage is thought
      to play an important role in aging and age-associated diseases such as
      hypertension and oxidative stress may function as a common trigger for activation
      of the senescence programme. In this regard, the role of telomeres in the onset,
      development and prognosis of hypertension has generated considerable interest.
      These structures may deteriorate in the onset and development of arterial
      hypertension in which their length may be a predictor of outcome. As telomere
      length by its nature is a marker of cell senescence, this parameter is of
      particular interest when studying the lifespan and fate of endothelial cells,
      cardiomyocytes and smooth muscle cells, especially so because telomere length
      seems to be regulated by various factors notably certain cardiovascular risk
      factors, such as smoking, sex and obesity that are associated with high levels of
      oxidative stress. This review focuses on the vascular effects of reactive oxygen
      species and the role of oxidative stress in hypertension- associated vascular
      damage. In addition it reviewes the considerable amount of data published
      recently on the role of telomeres to gain insights into the links between
      telomere length and hypertension, and assesses the usefulness of telomere length
      as a new marker of cardiovascular risk.

PMID- 23173584
TI  - Effect of aging on metabolic pathways in endothelial progenitor cells.
AB  - Age represents a significant risk factor for the onset and progression of
      cardiovascular disease, with the increase in life expectancy in developed
      countries going in parallel with increased incidence of such pathologies.
      Treatment strategies alternative or additive to pharmacological treatments are
      needed. The relationship between aging and progenitor cell-mediated repair is of
      great interest. Endothelial progenitor cells (EPC) mediate repair mechanisms for
      endothelial regeneration and maintenance, but they are subject to age-associated
      changes affecting negatively their number and/or function. Aim of this review is
      to examine the impact of age on EPC-mediated vascular repair, with a focus on the
      metabolic pathways involved and on the therapeutic targets with potential for
      attenuating this effect.

PMID- 23173585
TI  - Microvascular function/dysfunction downstream a coronary stenosis.
AB  - For decades coronary macrovascular atherosclerosis has been considered the
      principal manifestation of coronary heart disease, with most of our effort
      dedicated to identifying and removal of coronary stenosis. However, growing body
      of literature indicates that coronary microcirculation also contributes
      substantially to the pathophysiology of cardiovascular disease. An understanding
      of mechanisms regulating microvascular function is of critical importance in
      understanding its role in disease, especially because these regulatory mechanisms
      vary substantially across species, vascular bed and due to comorbidities. Indeed,
      the most obvious consequence of coronary stenosis is that it may limit blood
      supply to the dependent myocardium to the point of causing ischaemia during
      exercise or even at rest. However, this flow limiting effect is not only due to
      the passive hydraulic effect of a narrowed conduit, but also to active responses
      in the coronary microcirculation triggered by the presence of an epicardial
      stenosis. To understand this problem it is important to review the inter-related
      mechanisms that regulate flow to the left ventricular wall and modulate
      transmural distribution of flow. These regulatory mechanisms operate
      hierarchically and are heterogeneously distributed along the coronary vascular
      tree. It is also important to discuss the effect of myocardial performance in
      modulating both blood flow demands and coronary resistance. Some of the
      interactions between coronary stenosis and microcirculation are transient, like
      those documented in acute coronary syndromes or during percutaneous
      interventions. However, microcirculatory remodeling may be triggered by a chronic
      coronary stenosis, leading to a sustained impairment of blood supply even after
      successful removal of the epicardial stenosis. A deeper understanding of these
      phenomena may explain paradoxical findings in patients undergoing coronary
      revascularization, particularly when functional tests are used in their
      assessment. These aspects are discussed in detail in this review.

PMID- 23173586
TI  - Structural alterations of the retinal microcirculation in the "prehypertensive"
      high- normal blood pressure state.
AB  - The high-normal blood pressure (also known as prehypertension) is a clinical
      condition characterized by an increased cardiovascular risk as well as by the
      presence of target organ damage. This include an increased left ventricular mass,
      an endothelial dysfunction and an early renal functional and structural damage.
      Whether this is the case also for alterations of retinal vessels network, which
      are frequently detectable in established hypertension, is still largey undefined.
      The present paper, after discussing the main characteristics of the high-normal
      blood pressure state, will review the different approaches used throughout the
      years for assessing retinal microcirculatory network. Data collected by our group
      in subjects with high normal blood pressure will be also discussed, showing that
      arterial venular ratio values are reduced in this individuals with high-normal
      blood pressure and more so in established hypertension. These data indicate that
      retinal microvascular alterations 1) are of early appearance in the clinical
      course of hypertension and 2) are of frequent detection in the high-normal blood
      pressure state. The possible hemodynamic and non-hemodynamic mechanisms
      resposible for these structural alteations of the retinal microcirculation will
      be also discussed.

PMID- 23173587
TI  - Microvascular endothelial dysfunction in obesity and hypertension.
AB  - Endothelium plays a crucial role in modulating vascular function and structure,
      mainly by production of nitric oxide which protects the vasculature against the
      development of atherosclerosis and thrombosis. Traditional cardiovascular risk
      factors are characterized by endothelial dysfunction caused by an enhanced
      production of oxidative stress leading to destroy NO thus reducing its
      availability. A reduced endothelium-dependent relaxation is a predictor of
      cardiovascular events in high risk patients. Abdominal obesity is associated with
      microvascular endothelial dysfunction, through indirect mechanisms, such as
      insulin-resistance and the association with risk factors (including diabetes
      mellitus, hypertension and dyslipidemia), and directly, among others, by the
      production of adipokines and pro-inflammatory cytokines which in turn induce
      oxidative stress leading to a reduced NO availability. Several systems are
      amplified by the concomitant obesity and hypertension, thus generating a
      perpetual vicious circle which further contribute to the pathogenesis/progression
      of microvascular disease. Weight loss and modification of life-style ameliorate
      endothelial function in obese patients. It is conceivable that endothelial
      dysfunction might represent a complementary but crucial objective of a modern
      therapeutical approach leading to improve the prognosis in many patients,
      including obese patients, exposed to a high cardiovascular risk.

PMID- 23173588
TI  - Functional and structural alterations of large arteries: methodological issues.
AB  - Ultrasound assessment of vascular biomarkers has been implemented for screening,
      prevention and improvement of cardiovascular risk stratification beyond classical
      risk factors including smoking, diabetes, hypercholesterolemia and hypertension.
      Thus, the presence of vascular damage at the sub-clinical, asymptomatic stages
      can identify a "vulnerable" patient, and aid in implementing cardiovascular
      prevention strategies. Increased intima-media thickness of the common carotid
      artery is a well-known marker of early atherosclerosis, which significantly
      correlates with the development of coronary or cerebro-vascular disease. More
      recently, guidelines for cardiovascular prevention in hypertension also
      introduced other vascular parameters evaluating both mechanical and functional
      arterial properties of peripheral arteries. Increased arterial stiffness, which
      can be detected by ultrasound at the common carotid, has been shown to predict
      future cardiovascular events and it is already considered a subclinical target
      organ of hypertensive patients. Even earlier vascular abnormalities such as
      endothelial dysfunction in the peripheral arteries, detected as reduced flow
      mediated dilation of the brachial artery by ultrasound, have also been mentioned
      for their possible clinical use in the future. This manuscript reviews clinical
      evidence supporting the use of these different vascular markers for
      cardiovascular risk stratification, focusing on the need for an accurate, robust
      and reliable methodology for the assessment of vascular markers, which could
      improve their predictive value and increase their use in routine clinical
      practice.

PMID- 23173589
TI  - Device-based therapies for resistant hypertension.
AB  - Hypertension is universally considered the most detrimental among cardiovascular
      risk factors. Despite the overwhelming evidence of benefits deriving from
      lowering blood pressure, its control among the hypertensive population is still
      unsatisfactory. Resistant hypertension has a non negligible prevalence among
      hypertensive patients, and it is associated with a worse cardiovascular
      prognosis. There is need of new therapeutic approaches for reducing
      cardiovascular risk in this population. Sympathetic nervous system is known to
      play a major role in development and maintenance of essential hypertension, thus
      in the past decades several efforts have been made to counteract its
      overactivation. Novel non-pharmacological, promising approaches targeting
      sympathetic nervous system are now available, such as renal denervation and
      baroceptor-activating therapy. This review is aimed at describing essential
      clinical aspects of resistant hypertension, physiopatological basis of autonomic
      modulation as a target for hypertension treatment, and the available clinical
      evidence about efficacy and safety of device-based therapies for resistant
      hypertension. Present limitations and future perspectives were also considered.

PMID- 23173590
TI  - Sleep loss and hypertension: a systematic review.
AB  - Hypertension and insomnia are very common and often coexist. There is evidence to
      suggest that the increasing prevalence of arterial hypertension in the past
      decade might be related both to an increased prevalence of insomnia and to the
      decline of sleep duration due to modern lifestyle. The aim of this paper is to
      reconsider both the clinical evidence of the relationship between conditions of
      sleep loss and of perceived impairment in sleep quality with hypertension and the
      potential pathophysiological mechanisms underlying the biological plausibility of
      their relationship. Through a systematic search from MEDLINE, EMBASE, PsychINFO
      we selected articles, which reported experimental sleep deprivation designs, or
      studied sleep duration or insomnia and their relationship with blood pressure or
      hypertension in participants over 18 years. This analysis shows that experimental
      sleep deprivation, short sleep duration, and persistent insomnia are associated
      with increased blood pressure and increased risk of hypertension, even after
      controlling for other risk factors. Pathophysiological mechanisms underlying this
      association might be related to inappropriate arousal ("hyperarousal") due to an
      overactivation of stress system functions. According this hypothesis, prolonged
      sleep loss or alterations of sleep quality might act as a neurobiological and
      physiologic stressor that impair brain functions and contribute to allostatic
      load, compromising stress resilience and somatic health.

PMID- 23173591
TI  - Insulin resistance and endothelial dysfunction: a mutual relationship in
      cardiometabolic risk.
AB  - Cardiometabolic risk comprises a cluster of traditional and emerging factors that
      are good indicators of a patient's overall risk for type 2 diabetes and
      cardiovascular disease. The insulin resistance, a key feature common to obesity
      and type 2 diabetes, is associated with impaired vascular response and
      contributes to increased cardiovascular risk. Abnormal vascular insulin
      signalling induces endothelial dysfunction, the initial step of atherosclerotic
      process, characterized by attenuated nitric oxide-mediated vasodilatation and
      atherogenic response. Insulin resistance and endothelial dysfunction are two
      pathological conditions that can co-exist, even if their cause-effect
      relationship is not yet clarified. Multiple signaling pathways shared by insulin
      resistance and endothelial dysfunction include hyperinsulinemia, glucotoxicity,
      lipotoxicity, and inflammation. These mechanisms selectively impair PI3K
      dependent insulin in vascular endothelium harming endothelial balance and
      strengthening the evidence of the close association between metabolic and
      cardiovascular disease. The present review analyzes the close relationship
      between endothelial dysfunction and insulin resistance and explores the common
      mechanisms, with clinical considerations and pharmacological strategies.

PMID- 23173593
TI  - Cardiovascular molecular imaging: new methodological strategies.
AB  - Significant technical advances in small animal molecular imaging techniques and
      in imaging probes with high specificity for various molecular targets have been
      produced in the last ten years. Notwithstanding, the clinical applicability of
      molecular imaging proceeds slowly. In animal experiments, multimodality molecular
      imaging techniques based on hybrid scanners are increasing, providing more
      insight into path physiologic phenomena associated with cardiovascular disease.
      In parallel, we assisted in the development of a new generation of multi-imaging
      probes, such as PET/MRI probes, particularly effective in hybrid scanners. More
      recently, in order to gain in inherently low sensitivity of MRI, hyperpolarized
      magnetic resonance spectroscopy using hyperpolarized (13)C was proposed.
      Preliminary results obtained in experimental animal studies seem to confirm the
      potentialities of hyperpolarized (13)C magnetic resonance to monitor myocardial
      energetics. In this review the preclinical cardiovascular applications and the
      potential for clinical translation are discussed.

PMID- 23173592
TI  - Chronic hyperuricemia, uric acid deposit and cardiovascular risk.
AB  - Hyperuricemia is commonly associated with traditional risk factors such as
      dysglicemia, dyslipidemia, central obesity and abnormal blood pressure, i.e. the
      metabolic syndrome. Concordantly, recent studies have revived the controversy
      over the role of circulating uric acid, hyperuricemia, and gout as an independent
      prognostic factor for cardiovascular morbidity and mortality. In this regard,
      different studies also evaluated the possible role of xanthine inhibitors in
      inducing blood pressure reduction, increment in flow-mediated dilation, and
      improved cardiovascular prognosis in various patient settings. The vast majority
      of these studies have been conducted with either allopurinol or its active
      metabolite oxypurinol, i.e. two purine-like non-selective inhibitors of xanthine
      oxidase. More recently, the role of uric acid as a risk factor for cardiovascular
      disease and the possible protective role exerted by reduction of hyperuricemia to
      normal level have been evaluated by the use of febuxostat, a selective, non
      purine-like xanthine oxidase inhibitor. In this review, we will report current
      evidence on hyperuricemia in cardiovascular disease. The value of uric acid as a
      biomarker and as a potential therapeutic target for tailored old and novel
      "cardiometabolic" treatments will be also discussed.

PMID- 23173594
TI  - The economic costs for the control of cardiovascular risk: an overview.
AB  - Macroeconomic variables primarily related to the health care system are the
      result of two key factors. On the one hand, the results obtained for preserving
      the health of individuals improving, also, the quality of life and, on the other
      hand, the costs to be supported in order to reach these results. There is
      evidence that a balance between these two parameters must be obtained in an era
      of limited economic resources and, therefore, measures, which can achieve these
      variables, are under study. Cost-effectiveness ratio is the most economic factor
      analyzed still lending to define the relationship between costs and disease. With
      regard to cardiovascular risk, budgets not always in line with established
      expectations are under exam. Quantitative measures related to cost-effectiveness
      ratio as the estimate-score system, which sets specific scores for the symptoms
      of the disease, are studied to improve the budget that regulates costs and
      results on public health including cardiovascular risk characterized by a high
      frequency of adverse events.

PMID- 23173595
TI  - Modifying cardiovascular risk factors: new markers of cardiovascular damage.

PMID- 23173596
TI  - Building theories of knowledge translation interventions: use the entire menu of
      constructs.
AB  - BACKGROUND: In the ongoing effort to develop and advance the science of knowledge
      translation (KT), an important question has emerged around how theory should
      inform the development of KT interventions. DISCUSSION: Efforts to employ theory
      to better understand and improve KT interventions have until recently mostly
      involved examining whether existing theories can be usefully applied to the KT
      context in question. In contrast to this general theory application approach, we
      propose a 'menu of constructs' approach, where individual constructs from any
      number of theories may be used to construct a new theory. By considering the
      entire menu of available constructs, rather than limiting choice to the broader
      level of theories, we can leverage knowledge from theories that would never on
      their own provide a complete picture of a KT intervention, but that nevertheless
      describe components or mechanisms relevant to it. We can also avoid being forced
      to adopt every construct from a particular theory in a one-size-fits-all manner,
      and instead tailor theory application efforts to the specifics of the situation.
      Using audit and feedback as an example KT intervention strategy, we describe a
      variety of constructs (two modes of reasoning, cognitive dissonance, feed
      forward, desirable difficulties and cognitive load, communities of practice, and
      adaptive expertise) from cognitive and educational psychology that make concrete
      suggestions about ways to improve this class of intervention. SUMMARY: The 'menu
      of constructs' notion suggests an approach whereby a wider range of theoretical
      constructs, including constructs from cognitive theories with scope that makes
      the immediate application to the new context challenging, may be employed to
      facilitate development of more effective KT interventions.

PMID- 23173597
TI  - Laparocopic ventral hernia repair with primary transparietal closure of the
      hernial defect.
AB  - BACKGROUND: The treatment of ventral hernias is still a subject of debate. The
      affixing of a prosthesis and the subsequent introduction of laparoscopic
      treatment have reduced complications and recurrences. The high incidence of
      seromas and high costs remain open problems. METHODS: At our Department between
      January 2008 and December 2011, 87 patients (43 over 65 years), out of a total of
      132, with defects of wall whose major axis was less than 10 cm, or minor and
      multiple defects (Swiss-cheese defect) on an axis not exceeding 12 cm underwent
      laparoscopic ventral hernia repair (LVHR) with primary and transparietal closure
      of the hernial defect. Through small incisions in the skin we proceeded to close
      the parietal defect with sutures tied outside. Then the mesh was fixed as usual
      with double row of stitches and an overlap of 3-5 cm. RESULTS: In all patients,
      43 of them elderly, surgery was successfully conducted. The juxtaposition of the
      edges of the hernial defect has not been time consuming and has not developed new
      complications. The postoperative course was uneventful, with discharge on the
      third day, except in 5 patients. Were observed only small gaps and not the
      formation of large seromas. There were no infections wall. We do not have
      relapses, but some small and asymptomatic solutions continuously up to 2 cm at
      the sonographic study. In elderly patients the absence of dead space and the
      feeling of greater stability of the wall, early mobilization and pain control
      have facilitated the post-operative course. CONCLUSIONS: The positioning of
      sutures transcutaneous is simple and effective, the reduced incidence of seromas
      and the greater stability of the wall suggest to adopt this procedure fully.The
      possibility to close the margins of the defect may allow to change the size and
      setting of the mesh, since the absence of dead space allows to download
      physiologically tensions of the wall.

PMID- 23173598
TI  - Contrasting seasonal overlaps between primary and secondary growth are linked to
      wood anatomy in Mediterranean sub-shrubs.
AB  - Whole-plant approaches allow quantification of the temporal overlap between
      primary and secondary growth. If the amount of time available to grow is short,
      there may be a high temporal overlap between shoot growth and wood formation. We
      hypothesise that such overlap depends on the duration of the growing season and
      relates to wood anatomy. We evaluated wood anatomy, shoot longitudinal and radial
      growth rates, fine root production and the concentrations of non-structural
      carbohydrates (NSC) in the wood of six sub-shrub species growing in sites with
      contrasting climatic conditions (Lepidium subulatum, Linum suffruticosum, Salvia
      lavandulifolia, Satureja montana, Ononis fruticosa, Echinospartum horridum). Sub
      shrub species living in sites with a short growing season displayed a high
      overlap between aboveground primary and secondary growth and formed wide vessels,
      whereas species from the warmest and driest sites presented the reverse
      characteristics. The highest overlap was linked to a rapid shoot extension and
      thickening through the enhanced hydraulic conductivity provided by wide vessels.
      The reductions in NSC concentrations when growth peaked were low or moderate,
      indicating that sub-shrubs accumulate NSC in excess, as do trees. The temporal
      overlap among primary and secondary growth in woody plants may be connected to
      the duration and rates of shoot and wood growth, which in turn depend on the
      vessel lumen area. 

PMID- 23173599
TI  - Copper-ion-assisted growth of gold nanorods in seed-mediated growth: significant
      narrowing of size distribution via tailoring reactivity of seeds.
AB  - In the well-developed seed-mediated growth of gold nanorods (GNRs), adding the
      proper amount of Cu(2+) ions in the growth solution leads to significant
      narrowing in the size distribution of the resultant GNRs, especially for those
      with shorter aspect ratios (corresponding longitudinal surface plasmon resonance
      (LSPR) peaks shorter than 750 nm). Cu(2+) ions were found to be able to catalyze
      the oxidative etching of gold seeds by oxygen, thus mediating  subsequent growth
      kinetics of the GNRs. At proper Cu(2+) concentrations, the size distribution of
      the original seeds is greatly narrowed via  oxidative etching. The etched seeds
      are highly reactive and grow quickly into desired GNRs with significantly
      improved size distribution. A similar mechanism can be employed to tune the end
      cap of the GNRs. Except for copper ions, no observable catalytic effect is
      observed from other cations presumably due to their lower affinity to oxygen.
      Considering the widespread use of seed-mediated growth in the morphology
      controlled synthesis of noble metal nanostructures, the tailoring in seed
      reactivity we presented herein could be extended to other systems.

PMID- 23173600
TI  - Management of surgical procedures in children with severe FV deficiency:
      experience of 13 surgeries.
AB  - Homozygous severe factor V (FV) deficiency has a prevalence of around one per
      million. Even in patients with FV levels of <0.01 IU mL(-1)  there appears to be
      a variation in bleeding phenotype in that there is a subgroup of affected
      individuals who present in later childhood and have a relatively mild bleeding
      phenotype, but there are children who present as neonates with intracerebral
      bleeding events and who have a much more severe bleeding phenotype. The only
      available current FV replacement is in the form of fresh frozen plasma (FFP) or
      solvent detergent FFP. We present here our experience with surgical haemostatic
      cover for 13 surgeries in three children with severe FV deficiency.

PMID- 23173601
TI  - Involvement of spinal orexin A in the electroacupuncture analgesia in a rat model
      of post-laparotomy pain.
AB  - BACKGROUND: Orexin A (OXA, hypocretin/hcrt 1) is a newly discovered potential
      analgesic substance. However, whether OXA is involved in acupuncture analgesia
      remains unknown. The present study was designed to investigate the involvement of
      spinal OXA in electroacupuncture (EA) analgesia. METHODS: A modified rat model of
      post-laparotomy pain was adopted and evaluated. Von Frey filaments were used to
      measure mechanical allodynia of the hind paw and abdomen. EA at 2/15 Hz or 2/100
      Hz was performed once on the bilateral ST36 and SP6 for 30 min perioperatively.
      SB-334867, a selective orexin 1 receptor (OX1R) antagonist with a higher affinity
      for OXA than OXB, was intrathecally injected to observe its effect on EA
      analgesia. RESULTS: OXA at 0.3 nmol and EA at 2/15 Hz produced respective
      analgesic effects on the model (P<0.05). Pre-surgical intrathecal administered of
      SB-334867 30 nmol antagonized OXA analgesia and attenuated the analgesic effect
      of EA (P<0.05). However, SB-334867 did not block fentanyl-induced analgesia
      (P>0.05). In addition, naloxone, a selective opioid receptor antagonist, failed
      to antagonize OXA-induced analgesia (P>0.05). CONCLUSIONS: The results of the
      present study indicate the involvement of OXA in EA analgesia via OX1R in an
      opioid-independent way.

PMID- 23173602
TI  - Validation of an enzyme-linked immunosorbent assay for the quantification of
      human IgG directed against the repeat region of the circumsporozoite protein of
      the parasite Plasmodium falciparum.
AB  - BACKGROUND: Several pre-erythrocytic malaria vaccines based on the
      circumsporozoite protein (CSP) antigen of Plasmodium falciparum are in clinical
      development. Vaccine immunogenicity is commonly evaluated by the determination of
      anti-CSP antibody levels using IgG-based assays, but no standard assay is
      available to allow comparison of the different vaccines. METHODS: The validation
      of an anti-CSP repeat region enzyme-linked immunosorbent assay (ELISA) is
      described. This assay is based on the binding of serum antibodies to R32LR, a
      recombinant protein composed of the repeat region of P. falciparum CSP. In
      addition to the original recombinant R32LR, an easy to purify recombinant His
      tagged R32LR protein has been constructed to be used as solid phase antigen in
      the assay. Also, hybridoma cell lines have been generated producing human anti
      R32LR monoclonal antibodies to be used as a potential inexhaustible source of
      anti-CSP repeats standard, instead of a reference serum. RESULTS: The anti-CSP
      repeats ELISA was shown to be robust, specific and linear within the analytical
      range, and adequately fulfilled all validation criteria as defined in the ICH
      guidelines. Furthermore, the coefficient of variation for repeatability and
      intermediate precision did not exceed 23%. Non-interference was demonstrated for
      R32LR-binding sera, and the assay was shown to be stable over time. CONCLUSIONS:
      This ELISA, specific for antibodies directed against the CSP repeat region, can
      be used as a standard assay for the determination of humoral immunogenicity in
      the development of any CSP-based P. falciparum malaria vaccine.

PMID- 23173603
TI  - Rumen-protected methionine supplementation and fibre production in alpacas
      (Vicugna pacos).
AB  - Sulphur-containing amino acids are a crucial requirement for fibre production and
      may be supplemented in the diet of fibre-producing animals to stimulate fibre
      growth. The alpaca fibre industry is a developing industry in Australia with high
      variability in fibre production. To date, there is no evidence whether
      supplementing the diet of alpacas with sulphur amino acids improves fibre
      production. We hypothesised that supplementation with the rumen-protected sulphur
      amino acid, methionine would increase fibre growth in alpacas. Three groups of
      eight huacaya alpaca wethers were fed daily a maintenance diet supplemented with
      0, 2 or 4 g of rumen-protected methionine for 7 weeks. Fibre samples were taken
      at the beginning and end of the study with a blood sample taken by jugular
      venipuncture prior to feeding on the first day of each week. Methionine
      supplementation had no effect on fibre diameter (p = 0.92), fibre length (p =
      0.91) or fibre yield (p = 0.33). The change of season over the study affected
      plasma glucose (p < 0.001), plasma urea nitrogen (p < 0.001) and fibre diameter
      (p < 0.001). The indifference between groups may be due to the maintenance diet
      supplying sufficient levels of methionine, the lack of genetic potential of the
      experimental animals to respond to additional methionine or that the supplemental
      methionine was not protected in alpacas and deaminated for glucose production. 

PMID- 23173604
TI  - An antibody microarray analysis of serum cytokines in neurodegenerative
      Parkinsonian syndromes.
AB  - BACKGROUND: Microarray technology may offer a new opportunity to gain insight
      into disease-specific global protein expression profiles. The present study was
      performed to apply a serum antibody microarray to screen for differentially
      regulated cytokines in Parkinson's disease (PD), multiple system atrophy (MSA),
      progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS). RESULTS:
      Serum samples were obtained from patients with clinical diagnoses of PD (n =
      117), MSA (n = 31) and PSP/CBS (n = 38) and 99 controls. Cytokine profiles of
      sera from patients and controls were analyzed with a semiquantitative human
      antibody array for 174 cytokines and the expression of 12 cytokines was found to
      be significantly altered. In a next step, results from the microarray experiment
      were individually validated by different immunoassays. Immunoassay validation
      confirmed a significant increase of median PDGF-BB levels in patients with
      PSP/CBS, MSA and PD and a decrease of median prolactin levels in PD. However,
      neither PDGF-BB nor prolactin were specific biomarkers to discriminate PSP/CBS,
      MSA, PD and controls. CONCLUSIONS: In our unbiased cytokine array based screening
      approach and validation by a different immunoassay only two of 174 cytokines were
      significantly altered between patients and controls.

PMID- 23173605
TI  - Global diversity patterns and cross-taxa convergence in freshwater systems.
AB  - Whereas global patterns and predictors of species diversity are well known for
      numerous terrestrial taxa, our understanding of freshwater diversity patterns and
      their predictors is much more limited. Here, we examine spatial concordance in
      global diversity patterns for five freshwater taxa (i.e. aquatic mammals, aquatic
      birds, fishes, crayfish and aquatic amphibians) and investigate the environmental
      factors driving these patterns at the river drainage basin grain. We find that
      species richness and endemism patterns are significantly correlated among taxa.
      We also show that cross-taxon congruence patterns are often induced by common
      responses of taxa to their contemporary and historical environments (i.e.
      convergent patterns). Apart from some taxa distinctiveness (i.e. fishes), the
      'climate/productivity' hypothesis is found to explain the greatest variance in
      species richness and endemism patterns, followed by factors related to the
      'history/dispersion' and 'area/environmental heterogeneity' hypotheses. As
      aquatic amphibians display the highest levels of congruency with other taxa, this
      taxon appears to be a good 'surrogate' candidate for developing global freshwater
      conservation planning at the river drainage basin grain. 

PMID- 23173606
TI  - Therapeutic algorithms for chronic hepatitis C in the DAA era during the current
      economic crisis: whom to treat? How to treat? When to treat?
AB  - The advent of triple therapy (TT) with first-generation protease inhibitors
      boceprevir (BOC) and telaprevir (TVR) in addition to pegylated interferon and
      ribavirin resulted in a significant gain in terms of sustained virological
      response (SVR) when treating naive or previous treated patients with genotype 1
      (G1) chronic hepatitis C (CHC). This gain is partly balanced by the increased
      complexity of treatment and by the raised costs and risks of therapy, making
      necessary to optimize the indication to TT.Specifically, the identification of
      patient needing to TT over DT, the choice of the more correct therapeutic
      approach according to baseline and on treatment SVR predictors, and the timing of
      antiviral treatment, appear key issues to evaluate when considering TVR or BOC
      based therapies.Along this line, further efforts aimed to optimize the current TT
      regimens are still needed, especially in under-represented groups of patients in
      phase 3 studies such as those with cirrhosis, where post-marketing data are
      giving interesting evidences.

PMID- 23173607
TI  - Upregulation of mesencephalic astrocyte-derived neurotrophic factor in glial
      cells is associated with ischemia-induced glial activation.
AB  - BACKGROUND: Mesencephalic astrocyte-derived neurotrophic factor (MANF), a 20 kDa
      secreted protein, was originally derived from a rat mesencephalic type-1
      astrocyte cell line. MANF belongs to a novel evolutionally conserved family of
      neurotrophic factors along with conserved dopamine neurotrophic factor. In recent
      years, ever-increasing evidence has shown that both of them play a remarkable
      protective role against various injuries to neurons in vivo or in vitro. However,
      the characteristics of MANF expression in the different types of glial cells,
      especially in astrocytes, remain unclear. METHODS: The model of focal cerebral
      ischemia was induced by rat middle cerebral artery occlusion. Double-labeled
      immunofluorescent staining was used to identify the types of neural cells
      expressing MANF. Primarily cultured glial cells were used to detect the response
      of glial cells to endoplasmic reticulum stress stimulation. Propidium iodide
      staining was used to determine dead cells. Reverse transcription PCR and western
      blotting were used to detect the levels of mRNA and proteins. RESULTS: We found
      that MANF was predominantly expressed in neurons in both normal and ischemic
      cortex. Despite its name, MANF was poorly expressed in glial cells, including
      astrocytes, in normal brain tissue. However, the expression of MANF was
      upregulated in the glial cells under focal cerebral ischemia, including the
      astrocytes. This expression was also induced by several endoplasmic reticulum
      stress inducers and nutrient deprivation in cultured primary glial cells. The
      most interesting phenomenon observed in this study was the pattern of MANF
      expression in the microglia. The expression of MANF was closely associated with
      the morphology and state of microglia, accompanied by the upregulation of
      BIP/Grp78. CONCLUSIONS: These results indicate that MANF expression was
      upregulated in the activated glial cells, which may contribute to the mechanism
      of ischemia-induced neural injury.

PMID- 23173609
TI  - Hemoperitoneum presenting with the use of a topical hemostatic agent in oocyte
      retrieval: a case report.
AB  - INTRODUCTION: Hemoperitoneum may occur from an ovarian puncture point after
      oocyte retrieval. CASE PRESENTATION: We report a case of massive hemoperitoneum
      following transvaginal ultrasound-guided oocyte retrieval in a 33-year-old
      Caucasian woman. The bleeding required emergency laparoscopy because of active
      bleeding from the ovarian puncture point. Hemostasis was very difficult to
      achieve, and traditional operative procedures were not efficient. The only way to
      stop the bleeding was by using an absorbable fibrinogen and thrombin sealant
      sponge, which was applied around the ovary. During laparoscopy three pints of
      packed red blood were administered. No specific alteration of screening
      coagulation tests was found one month later. CONCLUSIONS: Hemostasis can be very
      difficult to achieve with traditional operative procedures. Topical hemostatic
      agents can be useful to preserve the ovary wherever possible.

PMID- 23173608
TI  - Changed adipocytokine concentrations in colorectal tumor patients and morbidly
      obese patients compared to healthy controls.
AB  - BACKGROUND: Obesity has been associated with increased incidence of colorectal
      cancer. Adipose tissue dysfunction accompanied with alterations in the release of
      adipocytokines has been proposed to contribute to cancer pathogenesis and
      progression. The aim of this study was to analyze plasma concentrations of
      several adipose tissue expressed hormones in colorectal cancer patients (CRC) and
      morbidly obese (MO) patients and to compare these concentrations to
      clinicopathological parameters. METHODS: Plasma concentrations of adiponectin,
      resistin, leptin, active plasminogen activator inhibitor (PAI)-1, monocyte
      chemotactic protein (MCP)-1, interleukin (IL)-1 alpha, and tumor necrosis factor
      (TNF)-alpha were determined in 67 patients operated on for CRC (31 rectal
      cancers, 36 colon cancers), 37 patients operated on for morbid obesity and 60
      healthy blood donors (BD). RESULTS: Compared to BD, leptin concentrations were
      lowered in CRC patients whereas those of MO patients were elevated. Adiponectin
      concentrations were only lowered in MO patients. Concentrations of MCP-1, PAI-1,
      and IL-1 alpha were elevated in both CRC and MO patients, while resistin and TNF
      alpha were similarly expressed in MO and CRC patients compared to BD. Resistin
      concentrations positively correlated with tumor staging (p<0.002) and grading
      (p=0.015) of rectal tumor patients. CONCLUSIONS: The results suggest that both MO
      and CRC have low-grade inflammation as part of their etiology.

PMID- 23173610
TI  - Why do few food-allergic adolescents treat anaphylaxis with adrenaline?-
      Reviewing a pressing issue.
AB  - Food allergic adolescents are at higher risk of fatal anaphylaxis than other
      children. Both allergen avoidance and maintaining access to adrenaline auto
      injectors (AAI) are key goals in effective food allergy management, for which
      written guidance is often supplied. However, adolescents are rarely sufficiently
      prepared to use adrenaline during anaphylaxis. It is likely that further didactic
      education would bring limited improvement in management in this population.
      Focused discussion of each adolescent's perspectives and current management
      practice may allow more effective behavioural strategies to be adopted. Key areas
      for appraisal include subjects' experiences after previous allergen exposure with
      reference to worst response, recognising specific symptoms requiring AAI
      administration, and appropriate priority being given to timeliness of
      administering adrenaline. Behavioural strategies should be discussed to increase
      AAI accessibility. Rigor of allergen avoidance should not be compromised by false
      reassurance of proximity to emergency medication or medical services. Food
      allergic adolescents are motivated by the psychological impact of their
      condition, which often makes them feel different to their peers and may result in
      bullying. Methods of appropriately empowering adolescents may be considered, such
      as involvement of close friends and lay organisations to support appropriate
      management. Open discussion is crucial in engaging with adolescents' reasoning
      for adopting their chosen management strategies. Further research is warranted to
      identify cognitive patterns associated with high-risk behaviour, and to design
      appropriate interventions for the augmentation of adolescent self-management
      skills.

PMID- 23173611
TI  - Efficacy and safety profile of a novel technique, ThuLEP (Thulium laser
      enucleation of the prostate) for the treatment of benign prostate hypertrophy.
      Our experience on 148 patients.
AB  - BACKGROUND: Over the past years laser technology has played a predominant role in
      prostate surgery, for the treatment of benign prostate hypertrophy (BPH). Various
      laser devices have been introduced in clinical practice, showing good results in
      terms of complications and urodynamic outcomes efficacy compared with TURP and
      Open Prostatectomy.In this study we describe the efficacy and the safety profile
      of a novel laser technique, ThuLEP (Thulium Laser Enucleation of Prostate) that
      permits a complete anatomical endoscopic enucleation of prostatic adenoma
      independently to prostate size. METHODS: 148 patients with a mean age of 68.2
      years were enrolled between September 2009 and March 2012 (36 months), and
      treated for BPH with ThuLEP. Every patient was evaluated at base line according
      to: Digital Rectal Examination (DRE), prostate volume, Post-Voided volume (PVR),
      International Prostate Symptoms Score (I-PSS), International Index of Erectile
      Function-5 (IIEF-5), Quality of Life (QoL), PSA values, urine analysis and urine
      culture, uroflowmetry. The same evaluation was conducted after a 12 month follow
      up. ThuLEP was performed by 2 expert surgeons. RESULTS: Our data showed a better
      post-operative outcome in terms of catheter removal, blood loss, TURP syndrome,
      clot retention and residual tissue compared to large series of TURP and OP. Only
      1.3% of patients had bladder wall injury during morcellation. I-PSS, Qmax,
      Prostate Volume, QoL and PVR showed a highly significant improvement at 12 month
      follow-up in comparison to preoperative assessment. CONCLUSION: ThuLEP represent
      an innovative option in patients with BPH. It is a size independent surgical
      endoscopic technique and it can be considered the real alternative, at this time,
      to TURP and even more to Open Prostatectomy for large prostate, with a complete
      removal of adenoma and with a low complication rate.

PMID- 23173612
TI  - Peripheral blood mono-nuclear cells implantation in patients with peripheral
      arterial disease: a pilot study for clinical and biochemical outcome of
      neoangiogenesis.
AB  - BACKGROUND: Substantial progresses in the management of peripheral arterial
      disease (PAD) have been made in the past two decades. Progress in the
      understanding of the endothelial-platelet interaction during health and disease
      state has resulted in better antiplatelet drugs that can prevent platelet
      aggregation, activation and thrombosis during angioplasty and stenting. A role in
      physiological and pathological angiogenesis in adults has been recently shown in
      bone marrow-derived circulating endothelial progenitors (BM-DCEPs) identified in
      the peripheral blood. These findings have paved the way for the development of
      therapeutic neovascularization techniques using endothelial progenitors. METHODS:
      This pilot study includes five patients, aged 60 to 75, with a history of
      claudication and recruited from September 2010 to February 2011 at the A.O.U.
      Federico II of Naples.PBMNCs have been implanted three times in the limb with the
      worst ABI value in all the patients included in the study.The clinical follow up
      was performed during the subsequent 12 months from the beginning of the
      treatment. RESULTS: In four patients there was a regression of ulcerative
      lesions.One patient's condition improved after the first implantation but later
      did not respond to the further treatments.All patients achieved a pain relief as
      judged by the numeric pain scale. Pain relief remained satisfactory in three
      patients for one year. Pain gradually returned to the pre-treatment level in two
      patients.All patients referred an ameliorating in their quality of life expressed
      even by an improvement in claudication free walking distance.These improvements
      are reflected also by intra-arterial digital subtraction angiography (IADSA) that
      shows an improvement of arterial vascularization. CONCLUSIONS: The data from this
      study suggest an efficacy of BM-DCEPs implantation in terms of improvement of the
      vascularization and quality of life in patients affected by Peripheral Arterial
      Disease. Nevertheless a double-blind placebo-controlled study is needed to
      confirm our findings.

PMID- 23173613
TI  - Nucleotide oligomerization domain 2 polymorphisms in patients with intestinal
      failure.
AB  - BACKGROUND: Nucleotide oligomerization domain 2 (NOD2) has been associated with
      intestinal immunity after the discovery that its polymorphisms are linked to
      Crohn's disease (CD). Intestinal failure (IF) represents a wider spectrum of
      diseases where intestinal homeostasis has been disrupted. AIM: To evaluate the
      prevalence of NOD2 mutations in a population with IF as well as its association
      with the different conditions causing this problem. METHODS: One hundred ninety
      two consecutive patients with IF and 103 healthy controls were genotyped for the
      three most common NOD2 polymorphisms. Genotypes were compared between the groups
      and were related to the entities causing IF. RESULTS: A high percentage (26%) of
      patients had at least one of the three most common NOD2 polymorphisms, while only
      a 4.8% of healthy controls had a mutant genotype. In patients with IF, specific
      mutations for the 702W, 908R and 1007fs alleles were 11, 5 and 12.5%,
      respectively, compared with 0.9% (P = 0.0003), 1.9% (P = 0.1) and 1.9% (P =
      0.001) in the control group. If we consider patients with any cause of IF other
      than CD, the percentage is still as high as 18.8%, with specific mutation
      frequencies of 7.6% (702W; P = 0.01), 5.8% (908R; P = 0.1) and 8.2% (1007fs; P =
      0.002). We could not establish an association between a NOD2 mutant genotype with
      any other specific clinical condition other than CD. CONCLUSION: Our finding
      supports the importance of NOD2 in the maintenance of intestinal immune
      homeostasis and may be important to a variety of intestinal stressors.

PMID- 23173614
TI  - Necrosis of the columella associated with nasal continuous positive airway
      pressure in a preterm infant.

PMID- 23173615
TI  - Graphene oxide as a quencher for fluorescent assay of amino acids, peptides, and
      proteins.
AB  - Understanding the interaction between graphene oxide (GO) and the biomolecules is
      fundamentally essential, especially for disease- and drug-related peptides and
      proteins. In this study, GO was found to strongly interact with amino acids
      (tryptophan and tyrosine), peptides (Alzheimer's disease related amyloid beta 1
      40 and type 2 diabetes related human islet amyloid polypeptide), and proteins
      (drug-related bovine and human serum albumin) by fluorescence quenching,
      indicating GO was a universal quencher for tryptophan or tyrosine related
      peptides and proteins. The quenching mechanism between GO and tryptophan (Trp) or
      tyrosine (Tyr) was determined as mainly static quenching, combined with dynamic
      quenching (Forster resonance energy transfer). Different quenching efficiency
      between GO and Trp or Tyr at different pHs indicated the importance of
      electrostatic interaction during quenching. Hydrophobic interaction also
      participated in quenching, which was proved by the presence of nonionic
      amphiphilic copolymer Pluronic F127 (PF127) in GO dispersion. The strong
      hydrophobic interaction between GO and PF127 efficiently blocked the hydrophobic
      interaction between GO and Trp or Tyr, lowering the quenching efficiency.

PMID- 23173616
TI  - Innate immune responses against Cryptosporidium parvum infection.
AB  - Cryptosporidium parvum infects intestinal epithelial cells and is commonly the
      parasite species involved in mammalian cryptosporidiosis, a major health problem
      for humans and neonatal livestock. In mice, immunologically mediated elimination
      of C. parvum requires CD4+ T cells and IFN-gamma. However, innate immune
      responses also have a significant protective role in both adult and neonatal
      mice. NK cells and IFN-gamma have been shown to be important components in
      immunity in T and B cell-deficient mice, but IFN-gamma-dependent resistance has
      also been demonstrated in alymphocytic mice. Epithelial cells may play a vital
      role in immunity as once infected these cells have increased expression of
      inflammatory chemokines and cytokines and demonstrate antimicrobial killing
      mechanisms, including production of NO and antimicrobial peptides. Toll-like
      receptors facilitate the establishment of immunity in mice and are involved in
      the development of inflammatory responses of infected epithelial cells and also
      dendritic cells.

PMID- 23173617
TI  - MirSNP, a database of polymorphisms altering miRNA target sites, identifies miRNA
      related SNPs in GWAS SNPs and eQTLs.
AB  - BACKGROUND: Numerous single nucleotide polymorphisms (SNPs) associated with
      complex diseases have been identified by genome-wide association studies (GWAS)
      and expression quantitative trait loci (eQTLs) studies. However, few of these
      SNPs have explicit biological functions. Recent studies indicated that the SNPs
      within the 3'UTR regions of susceptibility genes could affect complex
      traits/diseases by affecting the function of miRNAs. These 3'UTR SNPs are
      functional candidates and therefore of interest to GWAS and eQTL researchers.
      DESCRIPTION: We developed a publicly available online database, MirSNP
      (http://cmbi.bjmu.edu.cn/mirsnp), which is a collection of human SNPs in
      predicted miRNA-mRNA binding sites. We identified 414,510 SNPs that might affect
      miRNA-mRNA binding. Annotations were added to these SNPs to predict whether a SNP
      within the target site would decrease/break or enhance/create an miRNA-mRNA
      binding site. By applying MirSNP database to three brain eQTL data sets, we
      identified four unreported SNPs (rs3087822, rs13042, rs1058381, and rs1058398),
      which might affect miRNA binding and thus affect the expression of their host
      genes in the brain. We also applied the MirSNP database to our GWAS for
      schizophrenia: seven predicted miRNA-related SNPs (p < 0.0001) were found in the
      schizophrenia GWAS. Our findings identified the possible functions of these SNP
      loci, and provide the basis for subsequent functional research. CONCLUSION:
      MirSNP could identify the putative miRNA-related SNPs from GWAS and eQTLs
      researches and provide the direction for subsequent functional researches.

PMID- 23173618
TI  - The development of the spinal cord injury participation and quality of life (PAR
      QoL) tool-kit.
AB  - PURPOSE: Accurate descriptions of the impact of spinal cord injury (SCI)-related
      secondary health conditions (SHCs) on quality of life (QoL) are important to help
      guide the direction of resources and evaluation of therapies. However, selecting
      an appropriate outcome tool can be a challenge due to several clinical,
      theoretical and measurement issues. In order to help improve practices related to
      QoL measurement, a web-based Participation and QoL (PAR-QoL) tool-kit was
      designed to support researchers and clinicians with the outcome measure selection
      process. METHOD: The content of the PAR-QoL website ( www.parqol.com ) was
      developed through a series of systematic reviews of the SHC literature. Outcome
      tools identified in the studies were classified using Dijker's (2005) theoretical
      framework. RESULTS: A total of 199 studies were identified and categorized across
      eight different SHCs. Measures from the studies were extrapolated, and details
      regarding their [1] sensitivity to SHC impact [2], psychometric properties for
      SCI and [3] underlying QoL constructs were summarized onto a website.
      CONCLUSIONS: A better understanding of SHC impact on QoL will improve the quality
      of research, which in turn may provide better evidence for securing the necessary
      resources to help persons with SCI manage their health.

PMID- 23173620
TI  - Assessment of I-125 seed implant accuracy when using the live-planning technique
      for low dose rate prostate brachytherapy.
AB  - BACKGROUND: Low risk prostate cancers are commonly treated with low dose rate
      (LDR) brachytherapy involving I-125 seeds. The implementation of a 'live
      planning' technique at the Royal Adelaide Hospital (RAH) in 2007 enabled the
      completion of the whole procedure (i.e. scanning, planning and implant) in one
      sitting. 'Live-planning' has the advantage of a more reliable delivery of the
      planned treatment compared to the 'traditional pre-plan' technique (where patient
      is scanned and planned in the weeks prior to implant). During live planning, the
      actual implanted needle positions are updated real-time on the treatment planning
      system and the dosimetry is automatically recalculated. The aim of this
      investigation was to assess the differences and clinical relevance between the
      planned dosimetry and the updated real-time implant dosimetry. METHODS: A number
      of 162 patients were included in this dosimetric study. A paired t-test was
      performed on the D90, V100, V150 and V200 target parameters and the differences
      between the planned and implanted dose distributions were analysed. Similarly,
      dosimetric differences for the organs at risk (OAR) were also evaluated. RESULTS:
      Small differences between the primary dosimetric parameters for the target were
      found. Still, the incidence of hotspots was increased with approximately 20% for
      V200. Statistically significant increases were observed in the doses delivered to
      the OAR between the planned and implanted data; however, these increases were
      consistently below 3% thus probably without clinical consequences. CONCLUSIONS:
      The current study assessed the accuracy of prostate implants with I-125 seeds
      when compared to initial plans. The results confirmed the precision of the
      implant technique which RAH has in place. Nevertheless, geographical misses,
      anatomical restrictions and needle displacements during implant can have
      repercussions for centres without live-planning option if dosimetric changes are
      not taken into consideration.

PMID- 23173619
TI  - Longitudinal analysis of the lung microbiome in lung transplantation.
AB  - Lung transplant recipients experience poor long-term survival, largely due to
      chronic rejection. The pathogenesis of chronic rejection is incompletely
      understood, but bacterial colonization of the lung is associated with chronic
      rejection, while antibiotic use slows its progression. The lung harbors a
      bacterial community, termed the microbiome, which is present both in health and
      disease. We hypothesize that the lung microbiome will change following
      transplantation, and these changes may correspond to the development of
      rejection. Twelve bronchoalveolar lavage fluid (BALF) samples were obtained from
      four patients at three time points after transplantation, and two BALF samples
      were obtained from healthy, nontransplant controls. The microbiome of each sample
      was determined by pyrosequencing the 16S rRNA gene hypervariable 3 region. The
      data were analyzed using mothur, Ribosomal Database Project Classifier, Fast
      UniFrac, and Metastats. Transplanted lungs contained more bacterial sequences and
      demonstrated more microbial diversity than did control lungs. Bacteria in the
      phyla Proteobacteria (class Betaproteobacteria) predominated in the transplant
      samples. In contrast, the microbiome of the healthy lung consisted of the phyla
      Proteobacteria (class Gammaproteobacteria) and Firmicutes. The microbiome of the
      transplanted lung is vastly different from that of healthy lungs, mainly due to
      the presence of the family Burkholderiaceae in transplant samples.

PMID- 23173621
TI  - Acute kidney injury due to acute cortical necrosis following a single wasp sting.
AB  - Acute kidney injury (AKI) can develop after multiple wasp or bee stings. The
      etiology is the acute tubular necrosis secondary to shock, pigment toxicity,
      interstitial nephritis, or direct nephrotoxicity of venom. We report a 40-year
      old female who presented with oliguric AKI after a single wasp sting on her hand.
      Her history, examination, and investigations did not support any of the
      established causes of AKI in such settings. She did not improve with supportive
      management and dialysis, and kidney biopsy showed acute cortical necrosis (ACN).
      This is the first report of ACN after a single wasp sting.

PMID- 23173622
TI  - Death after an accidental fall of a 101 year old hospitalized patient. Medico
      legal implication of falling in geriatrics.
AB  - BACKGROUND: The case presented by the authors gives the opportunity to discuss
      the medico-legal issues related to lack of prevention of falls in elderly
      hospitalized patients. CASE PRESENTATION: A 101 year old Caucasian female was
      admitted to a surgery division for evaluation of abdominal pain of uncertain
      origin. During hospitalization, after bilateral bed rails were raised, she fell
      and reported a femoral fracture. Before surgical treatment of the fracture,
      scheduled for the day after injury, the patient reported a slight reduction in
      hemoglobin. She received blood transfusion but her general condition suddenly
      worsened; heart failure was observed and pulseless electrical activity was
      documented. The patient died 1 day after the fall. Patient relatives requested a
      judicial evaluation of the case.The case was studied with a methodological
      approach based on the following steps: 1) examination of clinical records; 2)
      autopsy; 3) evaluation of clinicians' behavior, in the light of necroscopic
      findings and a review of the literature. CONCLUSIONS: The case shows that an
      accurate evaluation of clinical and environmental risk factors should be always
      performed at the moment of admission also in surgery divisions. A
      multidisciplinary approach is always recommended also with the involvement of the
      family members. In some cases, as in this one a fall of the patient is expectable
      but not always avoidable. Physical restraint use should be avoided when not
      necessary and used only if there are no practical alternatives.

PMID- 23173623
TI  - Are we near a limit or can we get more safety from vehicle alcohol interlocks?

PMID- 23173624
TI  - Effect of dexmedetomidine on erythrocyte deformability during ischemia
      reperfusion injury of liver in diabetic rats.
AB  - AIM: The aim of this study is to evaluate the effect of dexmedetomidine on
      erythrocyte deformability during IR injury of liver in diabetic rats. METHODS:
      Twenty- eight Wistar Albino rats were included in the study after a 4 week
      streptozocin (65 mg/kg) treatment to observe the existence of diabetes. The
      animals were randomly assigned to one of the four experimental groups: GroupC and
      DC (sham-control group): The abdomen was dissected with a median laparotomy and
      the liver was collected. GroupDIR: The liver was collected after IR following the
      abdominal median laparotomy. GroupDIRD: The liver was collected after IR
      following the abdominal median laparotomy and 30 min of infusion of
      dexmedetomidine 100 ug/kg ip The deformability measurements were performed in
      erythrocyte suspensions containing Htc 5% in PBS buffer. RESULTS: The
      deformability index was significantly increased in diabetic rats, however it was
      similar in the GroupC and DIRD. It was significantly increased in the GroupDIR
      when compared to the GroupC, DIRD and DC. The relative resistance was increased
      in IR models. CONCLUSION: Erythrocyte deformability was damaged in rats having
      diabetes and IR injury. This injury might lead to further problems in
      microcirculation. It was shown that dexmedetomidine may be useful in enhancing
      the adverse effects of this injury (Tab. 1, Fig. 2, Ref. 41).

PMID- 23173625
TI  - Effects of diosmine-hesperidine on experimental colonic anastomosis.
AB  - AIM: Our goal was to determine the effects of a diosmine-hesperidine combination
      on wound healing in a rat model of colonic anastomosis. MATERIALS AND METHODS: In
      this study, 20 Wistar Albino female rats were randomized into four experimental
      groups containing five rats in each group. A segment of 1 cm of colon was excised
      4 cm proximally to the peritoneal reflection in all rats without carrying out any
      mechanical or antibacterial bowel preparation. Colonic anastomosis was performed
      with interrupted, inverting sutures of 6/0 polypropylene. Beginning from the
      first postoperative day, the rats in Groups II and IV received 100 mg/kg per day
      of diosmine-hesperidine via orogastic route by 4F fine feeding catheter. RESULTS:
      A significant difference was detected between groups in terms of their
      hydroxyproline levels (p<0.05); the hydroxyproline level of Group I was
      significantly lower than that of the other groups while no significant difference
      was noted between Groups II and III. CONCLUSION: The administration of diosmine
      hesperidine increased the amount of collagen and bursting pressures at the
      anastomotic site and thus had favorable influences on the healing of colonic
      anastomosis (Tab. 1, Fig. 3, Ref. 33).

PMID- 23173626
TI  - Protective effect of melatonin on lipid peroxidation in various tissues of
      diabetic rats subjected to an acute swimming exercise.
AB  - BACKGROUND: The present study aimed to explore the effect of melatonin
      administration on lipid peroxidation in various tissues of rats with streptozocin
      induced diabetes and subjected to an acute swimming exercise. METHODS: The study
      used 80 adult male rats, which were equally allocated to 8 groups: Group 1,
      general control; Group 2, melatonin-administered control; Group 3, melatonin
      administered diabetic control; Group 4, swimming control; Group 5, melatonin
      administered swimming; Group 6, melatonin-administered diabetic swimming; Group
      7, diabetic swimming; Group 8, diabetic control. Diabetic rats were administered
      3 mg/kg/day ip melatonin for 4 weeks. At the end of the study, the animals were
      decapitated to collect samples from liver, lung and spleen tissues, which were
      then analyzed to determine levels of liver MDA (nmol/gram/protein) and GSH
      (mg/g/protein). RESULTS: The highest MDA values in liver, lung and spleen tissues
      were obtained in the Group 7. The values in the Group 8 were lower than those in
      the Group 7, but higher than in all other groups. The Group 5 and 6 had the
      highest liver, lung and spleen GSH values. CONCLUSION: Results obtained from the
      study indicate that the increase in free radical production and the inhibition of
      antioxidant activity in diabetes and acute exercise are both prevented by
      melatonin administration (Tab. 2, Ref. 30).

PMID- 23173627
TI  - Oxidative stress and antioxidant activity of female rat liver tissue after
      sevoflurane anaesthesia: young versus old.
AB  - AIM: The aim of our study was to assess the evidence of oxidative stress in the
      rat liver tissue by studying enzymes, such as nitric oxide synthase (NOS),
      superoxide dismutase (SOD), glutathione-S transferase (GST) activity, and
      thiobarbutiric acid-reactive substances (TBARS) levels in young versus old female
      rats after sevoflurane anaesthesia. MATERIAL AND METHOD: The study involved 28
      female Wistar Albino rats. The rats were divided into the two groups [(Group I,
      n=14): Young sevoflurane group (Group I-YS, n=7); Young control group (Group I
      YC, n=7)], [(Group II, n=14): Old sevoflurane group (Group II-OS, n=7); Old
      control group (Group II-OC, n=7)]. Sevoflurane was administered at 2 % volume
      inspiratory concentration, 6 L.min-1 in 100 % O2 for 2 hours. The control groups
      were not subjected to any procedures. Accordingly, GST, SOD, and NOS enzyme
      activity and TBARS level, were studied in the liver tissue samples of the rats to
      determine the presence of oxidative stress (OS) and antioxidant activity.
      RESULTS: Following administration of sevoflurane anaesthesia; GST, SOD enzyme
      activity and TBARS level was significantly higher in the Group I-YS than in the
      Group I-YC and in the Group II-OS than in the Group II-OC. There was no
      difference between the groups when the mean NOS levels were compared. CONCLUSION:
      Although the results of our study are similar to the previous indicating that
      sevoflurane has the capacity to induce the oxidative stress; a new data has been
      recorded that sevoflurane has a similar effect on the OS level in aged and young
      female rat (Tab. 1, Fig. 4, Ref. 48).

PMID- 23173628
TI  - The evaluation of Candida albicans biofilms formation on silicone catheter, PVC
      and glass coated with titanium dioxide nanoparticles by XTT method and ATPase
      assay.
AB  - Lots of Candida albicans infections involve in biofilm formation on medical
      devices. This kind of biofilm can impede antifungal therapy and complicates the
      treatment of infectious diseases particularly in field of chronic diseases
      associated with implanted devices. This study has investigated the influence of
      treating silicone catheter, PVC and glass coated with Titanium dioxide (TiO2)
      nanoparticles on attachment of C. albicans. In this study TiO2 nanoparticles were
      synthesized from precursor TiCl4 and characterized by scanning electron
      microscopy (SEM) and X-ray diffraction (XRD) which showed TiO2 nanoparticles are
      70-100 nm in size. In the simplest model of biofilms formation, C. albicans
      isolates (ATCC10231) and (ATCC 76615) were grown on the surface of small disks of
      catheter, PVC and glass in a flat-bottomed 12-well plates and evaluated biofilm
      formation using ATP bioluminescence and tetrazolium salt (XTT) reduction assays.
      In addition, morphology of C. albicans biofilms after 48 h incubation was
      observed by SEM. Results indicated that there is a statistical difference between
      mean of coated samples especially catheter and glass before and after TiO2
      nanoparticles coating (p<0.05). In SEM analysis, C. albicans biofilm was more
      aggregated on the surface of glass and catheter than PVC and control groups and
      after treatment by these nanoparticles, catheter and glass both showed most
      significant decrease of C. albicans attachment in comparison to the control
      groups (Fig. 4, Ref. 23).

PMID- 23173629
TI  - Histological composition of lumbar disc herniations related to the type of
      herniation and to the age.
AB  - OBJECTIVES: To compare the data for histologic composition of the herniated disc
      material between different types of disc herniations and between patients of
      different age. BACKGROUND: Lots of studies have investigated the histologic
      composition of disc herniations. Few studies have examined the presence of
      granulation tissue related to the type of herniations and age of the subjects.
      METHODS: 120 patients divided in to two age groups underwent MR imaging before
      microsurgical removal of the herniations. Disc herniations were divided in to two
      groups, non migrated and large migrated disc herniations. The histologic
      assessment of the herniated material is done by dividing the intercellular matrix
      into four types. The existence of areas of granulation tissue and hyaline
      cartilage is evaluated too. RESULTS: The tissue composition showed significant
      differences between patients of different age. Areas of granulation tissue and
      neovascularisation are found in 12% of 64 protrusions and contained extrusions,
      and in 29% of 56 large migrated disc extrusions (p=0.029 ). In elderly patients
      the tissue composition changed with a significant decrease of prevailing nucleus
      pulposus composition in 7% of 60 (p=0.000) and a significant increase of
      prevailing fibrous tissue composition in 40% of 60 patients (p=0.000). Areas of
      granulation tissue and neovascularisation were found in 27% of 60 patients aged
      <= 50 and in 13% of 60 patients aged >50. CONCLUSIONS: The tissue composition of
      the herniated material showed more expressed differences between subjects of
      different age. Granulation tissue and neovascularisation were more frequent
      findings in large migrated disc herniations and in patients aged 35 to 50 years
      (Fig. 8, Ref. 22).

PMID- 23173630
TI  - Serum copper levels in benign and malignant thyroid diseases.
AB  - OBJECTIVE: To examine the changes in serum copper (Cu) levels in benign and
      malignant thyroid disease in humans. BACKGROUND: Thyroid hormones influence the
      metabolism of trace elements including copper. METHODS: 47 papillary thyroid
      cancer and 43 benign multinodular goitre patients who underwent total
      thyroidectomy and 37 healthy control subjects were included into this study. All
      of the patients and controls were females. Serum Cu levels were detected with
      atomic absorption spectrophotometer. RESULTS: In the papillary thyroid cancer
      group serum level of Cu was 131.61 +/- 33.9 MUg/dL before surgery and 120.81 +/-
      30.4 MUg/dL after 20 days from surgery. In the benign group serum Cu level was
      84.75 +/- 12.1 MUg/dL and 68.01 +/- 9.4 MUg/dL postoperatively.These results were
      compared to healthy control's value of 105.87 +/- 10.68 MUg/dL. In the papillary
      thyroid cancer group pre- and postoperative serum Cu level was significantly
      higher when compared to control group (p<0.05). Postoperative serum Cu level
      significantly decreased when compared to pre-operative level(p<0.05), in which,
      it was still higher than the control(p<0.05). In the benign group pre- and
      postoperative serum Cu level was significantly lower than in the control group
      (p<0.05).Postoperative serum Cu level significantly decreased when compared to
      pre-operative level in the benign group (p<0.05). CONCLUSION: This is a pioneer
      study to examine serum Cu level in benign and malignant thyroid patients compared
      to controls. In our small groups serum Cu levels increased in malignant thyroid
      patients and decreased in the benign group (Tab. 1, Ref. 18).

PMID- 23173631
TI  - Screening for metabolic syndrome within a minority ethnic group (adult Gypsy
      people) in Hungary.
AB  - BACKGROUND: Metabolic syndrome occurs more often among people living in poorer
      social conditions. The health status of the largest minority ethnic group in
      Hungary lags in many aspects behind that of the general population. METHODS: To
      estimate the prevalence of metabolic syndrome a screening was initiated in the
      city of Gyor among subjects aged 20-70 years who declared themselves as Gypsy.
      Subjects with known diabetes and cardiovascular disease were excluded. The
      diagnosis of metabolic syndrome was based on the ATP-III criteria. RESULTS: Among
      the 77 individuals screened (35 men, 42 women, age 46.9 +/- 10.6 years, x +/- SD)
      diabetes mellitus was found in 14 cases (18.2 %), and pre-diabetes (impaired
      fasting blood glucose (IFG) or impaired glucose tolerance (IGT) could be
      diagnosed in further 14 cases (18.2 %). Individual components of the metabolic
      syndrome occurred as follows: hypertension in 47 subjects (61.0 %), abnormal
      waist circumference in 40 individuals (51.9 %), abnormal HDL-cholesterol in 39
      cases (50.6 %), abnormal triglycerides in 35 individuals (45.5 %) and abnormal
      fasting blood glucose in 15 subjects (19.5 %). Within the cohort metabolic
      syndrome could be diagnosed in 39 individuals (50.6 %) without a significant
      gender difference (males 20/35 = 57.1 %; women: 19/42 = 45.2 %, p>0.05).
      CONCLUSION: The occurrence of metabolic syndrome and that of glucose intolerance
      is high among adult Gypsy people in Hungary. In order to recognise cardio
      metabolic risks and to prevent their cardiovascular consequences, continuous
      health promotion and adequate medical care should be provided for the Gypsy
      population in Hungary (Tab. 5, Ref. 32).

PMID- 23173632
TI  - Clinico-embryological submission of an unilateral anomalous presentation of
      axillary artery.
AB  - OBJECTIVES: Descriptions of the variant arterial pattern of upper limb are not
      exceptional and are therefore frequently reported in anatomy archives.
      BACKGROUND: A noteworthy deviation from the usual branching pattern was observed
      unilaterally in a single cadaver. This unique division of axillary artery (AA)
      was present on the right side in an adult human cadaver of Indian origin.
      RESULTS: The first part of axillary artery gave off the superior thoracic and
      thoraco-acromial arteries. Just proximal to the upper border of pectoralis minor
      the AA was observed to divide into two trunks a medial and a lateral. The lateral
      trunk continued into the brachium as the usual axillary artery where as the
      medial trunk displayed the other branches deep and distal to the pectoralis minor
      muscle. The remarkable feature was the wide caliber of the axillary artery where
      it bifurcated into two branches. An attempt has been made to dwell upon the
      embryological basis of the present anomaly. CONCLUSIONS: The relevance of
      anomalous arterial pattern of upper limb (U.L.) is realized while performing
      percutaneous arterial venous catheter insertion into subclavian vein via the
      infraclavicular route. We advocate a meticulous familiarization of the anatomy of
      axillary artery and its topographical relationship to other neurovascular
      structures for the operating plastic surgeon, anesthetist and radiologist (Fig.
      1, Ref. 12).

PMID- 23173633
TI  - A new surgical method of pilonidal sinus treatment: a bilaterally paralel
      elliptic fascio-cutaneous advancement flap technique.
AB  - OBJECTIVE: Pilonidal sinus disease (PSD) is a common chronic disease in young
      people, It is often associated with considerable discomfort and morbidity.
      BACKGROUND: We aimed to describe our new bilateral parallel elliptic fascio
      cutaneous advancement flap technique in PSD treatment and we assessed the
      technique's results in 57 patients. METHOD: This procedure consists of a
      bilateral parallel elliptical excision, mobilization of the fascio-cutaneous flap
      from the median line of the wound, fixation of the base of the flap to the
      sacrococcygeal fascia by method of overlapping, and suturing its edge to the
      lateral side. Finally, we closed the wound without tension in accord with the
      anatomical plane. RESULT: The mean age of the patients was 25.3 +/- 4 years.
      Complications such as infection, wound dehiscence, and seroma were detected in 2
      (3.5 %), 2 (3.5 %), and 3 (5.2 %) patients, respectively. The mean durations of
      hospitalization and absence from work were 2.4 +/- 3 and 12.6 +/- 3 days,
      respectively. The mean length of defects after operations was 14.4 +/- 1 cm and
      the mean width was 7.2 +/- 1 cm). Follow up period averaged 21.4 +/- 1.2 (range,
      12 to 72) months. Recurrence occurred in one (1.7 %) patient. included in this
      study. We detected a mild-degree wound dehiscence in patients with wound
      infection (n=2, 3.5 %). CONCLUSION: Our novel technique provided the patients
      with minimum postoperative morbidity, short hospital stay and reduced absence
      from work. In addition, the technique has a satisfying aesthetic outcome and a
      decreased recurrence rate. Moreover, the flap could be prepared easily. In the
      light of our results, we suggest that our novel surgical technique seems to be a
      reasonable method in treatment of PSD (Fig. 2, Ref. 24).

PMID- 23173634
TI  - MDCT angiography assessment of tetralogy of Fallot with atresic left pulmonary
      artery.
AB  - A 24-year-old female patient was admitted to clinic with a 10-year history of
      dyspnoea. A chest radiograph showed mild cardiomegaly and echocardiography
      revealed classic findings of Fallot's tetralogy (TOF). Multidetector-computed
      tomography (MDCT) angiography was performed to evaluate the additional vascular
      anomalies. MDCT undoubtedly revealed left pulmonary arterial atresia as well as
      complex intracardiac and vascular anatomic features of TOF. We described both
      image findings of MDCT angiography for TOF and additional vascular anomalies in
      this patient (Fig. 3, Ref. 8).

PMID- 23173635
TI  - A stroke patient with impairment of auditory sensory (echoic) memory.
AB  - A 42-year-old man suffered damage to the left supra-sylvian areas due to a stroke
      and presented with verbal short-term memory (STM) deficits. He occasionally could
      not recall even a single syllable that he had heard one second before. A study of
      mismatch negativity using magnetoencephalography suggested that the duration of
      auditory sensory (echoic) memory traces was reduced on the affected side of the
      brain. His maximum digit span was four with auditory presentation (equivalent to
      the 1st percentile for normal subjects), whereas it was up to six with visual
      presentation (almost within the normal range). He simply showed partial recall in
      the digit span task, and there was no self correction or incorrect reproduction.
      From these findings, reduced echoic memory was thought to have affected his
      verbal short-term retention. Thus, the impairment of verbal short-term memory
      observed in this patient was "pure auditory" unlike previously reported patients
      with deficits of the phonological short-term store (STS), which is the next
      higher-order memory system. We report this case to present physiological and
      behavioral data suggesting impaired short-term storage of verbal information, and
      to demonstrate the influence of deterioration of echoic memory on verbal STM. 

PMID- 23173636
TI  - Finding malaria hot-spots in northern Angola: the role of individual, household
      and environmental factors within a meso-endemic area.
AB  - BACKGROUND: Identifying and targeting hyper-endemic communities within meso
      endemic areas constitutes an important challenge in malaria control in endemic
      countries such like Angola. Recent national and global predictive maps of malaria
      allow the identification and quantification of the population at risk of malaria
      infection in Angola, but their small-scale accuracy is surrounded by large
      uncertainties. To observe the need to develop higher resolution malaria
      endemicity maps a predictive risk map of malaria infection for the municipality
      of Dande (a malaria endemic area in Northern Angola) was developed and compared
      to existing national and global maps, the role of individual, household and
      environmental risk factors for malaria endemicity was quantified and the spatial
      variation in the number of children at-risk of malaria was estimated. METHODS:
      Bayesian geostatistical models were developed to predict small-scale spatial
      variation using data collected during a parasitological survey conducted from May
      to August 2010. Maps of the posterior distributions of predicted prevalence were
      constructed in a geographical information system. RESULTS: Malaria infection was
      significantly associated with maternal malaria awareness, households with canvas
      roofing, distance to health care centre and distance to rivers. The predictive
      map showed remarkable spatial heterogeneity in malaria risk across the Dande
      municipality in contrast to previous national and global spatial risk models;
      large high-risk areas of malaria infection (prevalence >50%) were found in the
      northern and most eastern areas of the municipality, in line with the observed
      prevalence. CONCLUSIONS: There is remarkable spatial heterogeneity of malaria
      burden which previous national and global spatial modelling studies failed to
      identify suggesting that the identification of malaria hot-spots within seemingly
      mesoendemic areas may require the generation of high resolution malaria maps.
      Individual, household and hydrological factors play an important role in the
      small-scale geographical variation of malaria risk in northern Angola. The
      results presented in this study can be used by provincial malaria control
      programme managers to help target the delivery of malaria control resources to
      priority areas in the Dande municipality.

PMID- 23173638
TI  - Epidemiological features and specificities of HCV infection: a hospital-based
      cohort study in a university medical center of Calabria region.
AB  - The epidemiological status of HCV in Europe, and in particular in Mediterranean
      countries, is continuously evolving. The genotype distribution is related to
      improvement of healthcare conditions, expansion of intravenous drug use and
      immigration. We review and characterize the epidemiology of the distribution of
      HCV genotypes within Calabria, an area of Southern Italy. We focus on the pattern
      of distinct HCV genotype changes over the last 16 years; particularly subtype 1b
      and genotype 4. We collected data by evaluating a hospital-based cohort of
      chronic hepatitis C patients; in addition, we report an update including new
      patients enrolled during last eight months.

PMID- 23173637
TI  - Cross-cultural adaptation and validation of the South African Pain
      Catastrophizing Scale (SA-PCS) among patients with fibromyalgia.
AB  - BACKGROUND: Pain catastrophization has recently been recognized as a barrier to
      the healthy development of physical functioning among chronic pain patients.
      Levels of pain catastrophization in chronic pain patients are commonly measured
      using the Pain Catastrophizing Scale (PCS). OBJECTIVE: To cross-culturally adapt
      and validate the South African PCS (SA-PCS) among English-, Afrikaans- and Xhosa
      speaking patients with fibromyalgia living in the Cape Metropole area, Western
      Cape, South Africa. METHODS: The original PCS was cross-culturally adapted in
      accordance with international standards to develop an English, Afrikaans and
      Xhosa version of the SA-PCS using a repeated measures study design. Psychometric
      testing included face/content validity, internal consistency (Cronbach's alpha
      alpha), test-retest reliability (intraclass coefficient correlations-ICC),
      sensitivity-to-change and cross-sectional convergent validity (by comparing the
      adapted SA-PCS to related constructs). RESULTS: The cross-culturally adapted
      English, Afrikaans and Xhosa SA-PCS showed good face and content validity,
      excellent internal consistency (with Chronbach's alpha = 0.98, 0.98 and 0.97 for
      the English, Afrikaans and Xhosa SA-PCS, as a whole, respectively), excellent
      test-retest reliability (with ICC's of 0.90, 0.91 and 0.89 for the English,
      Afrikaans and Xhosa SA-PCS, respectively); as well as satisfactory sensitivity-to
      change (with a minimum detectable change of 8.8, 9.0 and 9.3 for the English,
      Afrikaans and Xhosa SA-PCS, respectively) and cross-sectional convergent validity
      (when compared to pain severity as well as South African versions of the Tampa
      scale for Kinesiophobia and the revised Fibromyalgia Impact Questionnaire).
      CONCLUSION: The SA-PCS can therefore be recommended as simple, efficient, valid
      and reliable tool which shows satisfactory sensitivity-to-change and cross
      sectional convergent validity, for use among English, Afrikaans and Xhosa
      speaking patients with fibromyalgia attending the public health sector in the
      Western Cape area of South Africa.

PMID- 23173639
TI  - Looking forward--glancing back.

PMID- 23173640
TI  - Relationship between waist circumference and supine abdominal height measured at
      different anatomical sites and cardiometabolic risk factors in older women.
AB  - OBJECTIVES: To measure waist circumference (WC) and supine abdominal height (SAH)
      at different anatomic sites and to assess the relationship with cardiometabolic
      risk factors in women aged >60 years. METHODS: The present study included 113
      women from Vicosa, Minas Gerais, Brazil. The evaluations comprised
      anthropometric, biochemical and haemodynamic measurements. Different anatomical
      sites were used to measure WC: (i) the midpoint between the last rib and iliac
      crest; (ii) umbilical level; (iii) immediately above the iliac crests; and (iv)
      the narrowest point between the last rib and the iliac crest. Measurements were
      also taken at different anatomic sites for SAH: (i) the midpoint between the
      iliac crests; (ii) umbilical level; (iii) higher abdominal diameter; and (iv) the
      narrowest point between the last rib and the iliac crest. RESULTS: It was found
      that 35.4% of women were overweight, and the area (SE) body mass index was 25.8
      (4.2) kg/m(2). WC at the umbilical level [area (SE) area under the curve (AUC) =
      0.694 (0.079)] and SAH at the midpoint between the iliac crests [AUC = 0.747
      (0.076)] showed the largest areas under the receiver operating characteristic
      curve (P < 0.05) with respect to the identification of cardiometabolic risk
      factors associated with the metabolic syndrome (MS) where, of the two measures,
      SAH showed the greatest predictive potential. CONCLUSIONS: The results obtained
      in the present study suggest that, for the assessment of older women, the
      umbilical level and the midpoint between the iliac crests should used to measure
      WC and SAH, respectively. SAH showed the greatest predictive power for
      cardiometabolic risk factors associated with the MS in older women.

PMID- 23173643
TI  - Vitamin D receptor gene polymorphism and cardiovascular risk variables in elderly
      Polish subjects.
AB  - The aim of this work was to evaluate whether the FokI and BsmI polymorphisms of
      the VDR gene are associated with anthropometric and biochemical features of
      cardiovascular disease (CVD) in a Caucasian population aged over 65, participants
      of the Polish PolSenior study. We performed the study on randomly selected
      subjects: 427 women and 454 men aged over 65. Measurements of anthropometric
      parameters were carried out and biochemical parameters were estimated using
      commercial kits. VDR polymorphisms (rs10735810, rs1544410) were genotyped by PCR
      and FRLP. The prevalence of BsmI genotypes was 50% Bb, 23% bb, 27% BB in women
      and 48% Bb, 20% bb, 32% BB in men. The prevalence of FokI was 48% Ff, 22% ff, 30%
      FF in women and 50% Ff, 18% ff, 32% FF in men. The women bearing the rare allele
      b differ in homeostatic model assessment (HOMA) (p < 0.049) from women bearing
      common allele B, and the men differ in insulin level (p < 0.047) and HOMA (p <
      0.017). There were no significant differences in anthropometric or biochemical
      parameters between genotypes in FokI in female and male groups. The common allele
      B is connected with biochemical risk factors of CVD in older Caucasian men and
      women.

PMID- 23173644
TI  - Mixotrophic organisms become more heterotrophic with rising temperature.
AB  - The metabolic theory of ecology predicts that temperature affects heterotrophic
      processes more strongly than autotrophic processes. We hypothesized that this
      differential temperature response may shift mixotrophic organisms towards more
      heterotrophic nutrition with rising temperature. The hypothesis was tested in
      experiments with the mixotrophic chrysophyte Ochromonas sp., grown under
      autotrophic, mixotrophic and heterotrophic conditions. Our results show that (1)
      grazing rates on bacterial prey increased more strongly with temperature than
      photosynthetic electron transport rates, (2) heterotrophic growth rates increased
      exponentially with temperature over the entire range from 13 to 33  degrees C,
      while autotrophic growth rates reached a maximum at intermediate temperatures and
      (3) chlorophyll contents during mixotrophic growth decreased at high temperature.
      Hence, the contribution of photosynthesis to mixotrophic growth strongly
      decreased with temperature. These findings support the hypothesis that mixotrophs
      become more heterotrophic with rising temperature, which alters their functional
      role in food webs and the carbon cycle.

PMID- 23173645
TI  - The impact of MRI on stroke management and outcomes: a systematic review.
AB  - RATIONALE, AIMS AND OBJECTIVES: Magnetic resonance imaging (MRI) is widely used
      in stroke evaluation and is superior to computed tomography for the detection of
      acute ischaemia. We sought to evaluate the evidence that conventional MRI
      influences doctor management or patient outcomes in routine care. METHODS: We
      systematically searched PubMED, EMBASE and proceedings of the International
      Stroke Conference. Studies were included if they included patients presenting
      with possible stroke syndromes and they reported MRI results and resulting
      changes in management or outcome. Multiple reviewers determined
      inclusion/exclusion for each study, abstracted study characteristics and assessed
      study quality. RESULTS: Of 1813 articles screened, nine studies met inclusion
      criteria. None were randomized controlled trials, cohort studies or case-control
      studies. We found little evidence that MRI affects outcomes - one single-centre
      case series presented three patients. The remaining articles were studies of
      diagnostic tests or vignette-based studies that described changes in doctor
      management attributed to MRI. In the studies that suggested MRI influenced
      management, it did so in two ways. First, MRI distinguished stroke from mimics
      (e.g. brain tumours), thus enabling more appropriate selection of therapies.
      Second, even when MRI confirmed a suspected stroke diagnosis, it sometimes
      provided information (on stroke mechanism, localization, timing or
      pathophysiology) that influenced management. CONCLUSIONS: The impact of MRI on
      management and outcomes in stroke patients has been inadequately studied. Further
      research is needed to understand how MRI may productively affect stroke
      management and outcomes.

PMID- 23173647
TI  - Editorial: Developmental trajectories of intimate social relations and emotion
      regulation skills--a bi-directional interdependence.

PMID- 23173646
TI  - The role of stem cell factor and granulocyte-colony stimulating factor in
      treatment of stroke.
AB  - Stroke is a serious cerebrovascular disease that causes high mortality and
      persistent disability in adults worldwide. Stroke is also an enormous public
      health problem and a heavy public financial burden in the United States.
      Treatment for stroke is very limited. Thrombolytic therapy by tissue plasminogen
      activator (tPA) is the only approved treatment for acute stroke, and no effective
      treatment is available for chronic stroke. Developing new therapeutic strategies,
      therefore, is a critical need for stroke treatment. This article summarizes the
      discovery of new routes of treatment for acute and chronic stroke using two
      hematopoietic growth factors, stem cell factor (SCF) and granulocyte-colony
      stimulating factor (G-CSF). In a study of acute stroke, SCF and G-CSF alone or in
      combination displays neuroprotective effects in an animal model of stroke. SCF
      appears to be the optimal treatment for acute stroke as the functional outcome is
      superior to G-CSF alone or in combination (SCF+G-CSF); however, SCF+G-CSF does
      show better functional recovery than G-CSF. In a chronic stroke study, the
      therapeutic effects of SCF and G-CSF alone or in combination appear differently
      as compared with their effects on the acute stroke. SCF+G-CSF induces stable and
      long-lasting functional improvement; SCF alone also improves functional outcome
      but its effectiveness is less than SCF+G-CSF, whereas G-CSF shows no therapeutic
      effects. Although the mechanism by which SCF+G-CSF repairs the brain in chronic
      stroke remains poorly understood, our recent findings suggest that the SCF+G-CSF
      induced functional improvement in chronic stroke is associated with a
      contribution to increasing angiogenesis and neurogenesis through bone marrow
      derived cells and the direct effects on stimulating neurons to form new neuronal
      networks. These findings would assist in developing new treatment for stroke. The
      article presents some promising patents on role of stem cell factor and
      granulocyte-colony stimulating factor in treatment of stroke.

PMID- 23173648
TI  - Quality of life and depression in a cohort of female patients with chronic
      disease.
AB  - BACKGROUND: Differences in health-related quality of life perception in patients
      with chronic disease may depend on pre-existing differences in personality
      profile. The purpose of the study was to investigate in a cohort of female
      patients with chronic diseases the relationship between the Quality of Life
      perception and the potential presence of depressive symptoms. PATIENTS AND
      METHODS: Female patients with chronic diseases were enrolled in the study.
      Exclusion criteria were diagnosis of psychopathological condition, treatment with
      psychoactive substances.Methodological approach was based on administration of
      the following test. Short Form health survey SF-36, Symptom Check List SCL-90-R,
      Satisfaction Profile test (SAT-P) and Beck Depression Inventory-II (BDI-II). The
      Pearson correlation coefficient was used to evaluate the relationship between
      depressive symptoms and Quality of life as assessed by psychometric test.
      RESULTS: 57 patients, aged 52(+/- 3,4), responded to inclusion criteria. 57% of
      patients had a diagnosis of functional dyspepsia or gastro-oesophageal reflux not
      complicated, and the remaining 43% musculoskeletal diseases. The statistical
      analysis showed an inverse correlation between the variable Bodily Pain of the SF
      36 and the variable Depression scales of the SCL-90-R.In a second phase another
      sample of female patients was enrolled in the study. 64 patients, aged 49(+/-
      3,2), responded to inclusion criteria.Another significant negative correlation
      was found between the Somatic-Affective factor of the BDI-II and the scale
      Physical Functioning of the SAT-P. DISCUSSIONS: In female patients with chronic
      disease depressive symptoms resulted influenced by pain and vice versa. The
      treatment of depressive symptoms could improve the quality of life of patients.

PMID- 23173649
TI  - Effect of branched-chain amino acid-enriched nutritional supplementation on
      interferon therapy in Japanese patients with chronic hepatitis C virus infection:
      a retrospective study.
AB  - BACKGROUND: The aims of this study were to evaluate the effects of nutritional
      supplementation with branched-chain amino acids (BCAA) with zinc component
      (Aminofeel(r)) on adherence to and outcome of therapy in patients treated with
      interferon (IFN) for chronic hepatitis C and cirrhosis and to determine whether
      to recommend the supplement. METHODS: In this retrospective study, 51 patients
      who received IFN therapy were investigated among 203 consecutive patients who
      visited our hospital and were advised regarding the potential benefit of taking
      Aminofeel(r). Each patient was free to choose whether to purchase and take
      Aminofeel(r). RESULTS: Twenty four patients (group 1-A) took Aminofeel(r) during
      standard IFN therapy and 13 (group 1-B) did not. Low-dose, long-term IFN
      (maintenance) therapy, mainly peglated (Peg)-IFN alpha 2a, was administered to 14
      patients who were difficult to treat, because of no effect or harmful side
      effects with standard IFN therapy, and who had advanced liver fibrosis. Among the
      14, 11 patients (group 2-A) took Aminofeel(r) and 3 (group 2-B) did not. The
      prevalence of obesity was significantly higher (P=0.04) in group 1-A than in
      group 1-B. The rate of adherence to IFN therapy was higher in group 1-A (83.3%)
      than in group 1-B (53.8%, P=0.05). There were no significant differences between
      the two groups in the rates of sustained virological response (SVR) to IFN
      therapy. According to multivariate analysis, two factors, SVR and intake of
      Aminofeel(r), were associated with successful adherence to IFN therapy. The
      adjusted odds ratios for these two factors were 13.25 and 12.59, respectively,
      and each was statistically significant. The SVR rate of maintenance IFN therapy
      was in 18.2% group 2-A and 0% in group 2-B. CONCLUSION: Our data show that BCAA
      intake is useful for adherence to and effect of IFN therapy for patients with
      chronic hepatitis C. Nutritional supplementation with BCAA seems to be useful for
      HCV-infected patients receiving IFN therapy because it is impossible to introduce
      standard treatment for all patients among Japan's aging population.

PMID- 23173651
TI  - Hypoxia-inducible factor-1 as a therapeutic target in cancer.
AB  - Hypoxia-inducible factor-1 (HIF-1) is a transcription factor that immortalizes
      tumors by inducing key genes in cancer biology, including angiogenesis,
      glycolysis, invasion, and metastasis. Overexpression of HIF-1alpha is thus
      associated with resistance to cancer chemotherapy and increased patient mortality
      in several cancer phenotypes. In the present review, we summarize the role of
      intratumoral hypoxia and bioactive lipids in enhancing HIF-1 activity, critically
      discussing the potential for HIF-1alpha inhibitors in cancer chemotherapy.
      Considering preclinical studies, HIF-1 inhibitors appear to have antitumor
      effects and thus represent a novel therapeutic strategy.

PMID- 23173650
TI  - Observational study: daily treatment with a new compound "Tradamixina" plus
      serenoa repens for two months improved the lower urinary tract symptoms.
AB  - BACKGROUND: Lower urinary tract symptoms (LUTS) are associated with great
      emotional costs to individuals and substantial economic costs to society. This
      study seeks to evaluate the effect of a new natural compound "Tradamixina plus
      Serenoa Repens" in order to improve lower urinary tract symptoms. METHODS: 100
      patients (>= 45 years) who had had LUTS/BPH for >6 mo at screening and with IPSS 
      The international Prostate symptom scores- >= 13 and maximum urinary flow rate
      (Qmax) >= 4 to <= 15 ml/s. were recruited. The compound "Tradamixina plus Serenoa
      Repens" (80 mg of Alga Ecklonia Bicyclis, 100 mg of Tribulus Terrestris and 100
      mg of D-Glucosamine and N-Acetyl-D-Glucosamine plus 320 mg of Serenoa Repens) was
      administered daily for 2 months. At visit and after 60 days of treatment patients
      were evaluated by means of detailed medical urological history, clinical
      examination, laboratory investigations (total PSA), and instrumental examination
      like urolfowmetry. Efficacy measures included IPSS-International Prostate Sympto,
      BPH Impact Index (BII), Quality-of-Life (QoL) Index. Measures were assessed at
      baseline and end point (12 wk or end of therapy) and also at screening, 1 and 4
      wk for IPSS, and 4 wk for BII. Statistical significance was interpreted only if
      the results of the preceding analysis were significant at the 0.05 level.
      RESULTS: After 2 months of treatment the change from baseline to week 12 relative
      to "Tradamixina plus Seronea Repens" in total IPSS and Qol was statistically
      significant. Differences from baseline in BII were statistically significant for
      "Tradamixina plus Seronea Repens" above all differences in BII were also
      significant at 4 wk (LSmean +/- SE: -0.8 +/- 0.2). In the distribution of
      subjects over the PGI-I and CGI-I response categories were significant
      for"Tradamixina plus Seronea Repens" (PGI-I: p = 0.001; CGI-I). We also observed
      a decrease of total PSA. CONCLUSION: The daily treatment with a new compound
      "Tradamixina plus Serenoa Repens" for 2 months improved the male sexual function
      , it improved the bother symptoms which affect the patient's quality of life ,
      improved uroflowmetric parameters, and we also observed a decrease of serum PSA
      level.

PMID- 23173652
TI  - Plasma-mediated immune suppression: a neonatal perspective.
AB  - Plasma is a rich mixture of immune regulatory factors that shape immune cell
      function. This immunomodulatory role of plasma is especially important in
      neonates. To maintain in utero feto-maternal tolerance and to allow for microbial
      colonization after birth, the neonatal immune system is biased against pro
      inflammatory responses while favoring immune suppression. Therefore, the neonatal
      period provides a unique opportunity to study the physiologic mechanisms
      regulating the immune system. Several recent studies in neonates have identified
      plasma factors that play a key role in immune regulation. Insight into immune
      regulation by neonatal and adult plasma may have clinical implications, because
      plasma is easily accessible, affordable, and widely available. Herein, we review
      plasma-mediated immune regulation, with specific focus on neonatal plasma. We
      discuss how immune suppression is a key function of plasma and provide a
      systematic overview of the published literature regarding plasma-derived immune
      suppressive proteins, lipids, purines, and sugars. Finally, we outline how immune
      regulation by these factors, which are particularly abundant in neonatal plasma,
      may eventually be used to treat immune-mediated diseases, such as autoimmune,
      allergic, and inflammatory diseases.

PMID- 23173653
TI  - Comparison of free-solution and surface-immobilized molecular interactions using
      a single platform.
AB  - While it is generally accepted that surface immobilization affects the binding
      properties of proteins, it has been difficult to quantify these effects due to
      the lack of technology capable of making affinity measurements with species
      tethered and in free solution on a single platform. Further, quantifying the
      interaction of binding pairs with widely differing masses has also been
      challenging, particularly when it is desirable to tether the high molecular
      weight protein. Here we describe the use of backscattering interferometry (BSI)
      to quantify the binding affinity of mannose and glucose to concanavalin A (ConA),
      a 106 KDa homotetramer protein, in free solution using picomoles of the protein.
      Using the same platform, BSI, we then studied the effect on the binding constants
      of the ConA-carbohydrate interactions upon chemically immobilizing ConA on the
      sensor surface. By varying the distances (0, 7.17, and 20.35 nm) of the ConA
      tether and comparing these results to the free-solution measurements, it has been
      possible to quantify the effect that protein immobilization has on binding. Our
      results indicate that the apparent binding affinity of the sugar-lectin pair
      increases as the distance between ConA and the surface decreases. These
      observations could lend insight as to why the affinity values reported in the
      literature sometimes vary significantly from one measurement technique to
      another.

PMID- 23173655
TI  - What I should like to know about team nursing.

PMID- 23173656
TI  - Patient education outcomes in surgery: a systematic review from 2004 to 2010.
AB  - RATIONALE AND OBJECTIVES: In 2004, Johansson and colleagues, in their systematic
      review covering the years 1990-2003, documented education interventions and their
      effectiveness in the treatment of surgical patients. While they provide a review
      of the state of knowledge until 2003, recent trends in preoperative education and
      its effects on postoperative patients' outcomes have not been documented in a
      systematic review. The aim of this study was to describe preoperative educational
      interventions (including content and delivery time) and postoperative outcomes as
      considered in studies evaluating the effectiveness for patients undergoing major
      surgery published from 2004 to 2010. METHODS: A systematic review of preoperative
      education and its effects on postoperative patient outcomes was undertaken. A
      search was conducted of the PubMed, CINAHL and EBMR databases, including the
      Cochrane Central Register of Controlled Trials. Randomised controlled trials, or
      at least clinical trials including pre-/post-test evaluations, with educational
      interventions performed by nurses preoperatively and outcomes evaluated
      postoperatively, and written in English, were included. RESULTS: A total of 19
      studies involving 3944 patients were retrieved. Of these, 12 were randomised
      controlled trials. Interventions were based on verbal education, on
      written/visual education, or both. The content of interventions varied widely.
      Frequent outcomes evaluated were anxiety, knowledge, pain and length of stay.
      Objective knowledge (what a patient retains from education) was the only positive
      outcome influenced by education. CONCLUSIONS: Current trends in preoperative
      education are: scheduling education early; increased frequency of message
      exposure through several interventions and/or reinforcements; content frequently
      addressing postoperative management; the measurement of outcomes such as
      patients' cognitive, experiential and biophysiological aspects. Both the clinical
      and research implications that emerged from the findings are discussed.

PMID- 23173654
TI  - Wound repair and anti-inflammatory potential of Lonicera japonica in excision
      wound-induced rats.
AB  - BACKGROUND: Lonicera japonica Thunb. (Caprifoliaceae), a widely used traditional
      Chinese medicinal plant, is used to treat some infectious diseases and it may
      have uses as a healthy food and applications in cosmetics and as an ornamental
      groundcover. The ethanol extract of the flowering aerial parts of L. japonica
      (LJEE) was investigated for its healing efficiency in a rat excision wound model.
      METHODS: Excision wounds were inflicted upon three groups of eight rats each.
      Healing was assessed by the rate of wound contraction in skin wound sites in rats
      treated with simple ointment base, 10% (w/w) LJEE ointment, or the reference
      standard drug, 0.2% (w/w) nitrofurazone ointment. The effects of LJEE on the
      contents of hydroxyproline and hexosamine during healing were estimated. The
      antimicrobial activity of LJEE against microorganisms was also assessed. The in
      vivo anti-inflammatory activity of LJEE was investigated to understand the
      mechanism of wound healing. RESULTS: LJEE exhibited significant antimicrobial
      activity against Staphylococcus aureus, Staphylococcus epidermidis, Escherichia
      coli, Candida albicans, and Candida tropicalis. The ointment formulation prepared
      with 10% (w/w) LJEE exhibited potent wound healing capacity as evidenced by the
      wound contraction in the excision wound model. The contents of hydroxyproline and
      hexosamine also correlated with the observed healing pattern. These findings were
      supported by the histopathological characteristics of healed wound sections, as
      greater tissue regeneration, more fibroblasts, and angiogenesis were observed in
      the 10% (w/w) LJEE ointment-treated group. The results also indicated that LJEE
      possesses potent anti-inflammatory activity, as it enhanced the production of
      anti-inflammatory cytokines that suppress proinflammatory cytokine production.
      CONCLUSIONS: The results suggest that the antimicrobial and anti-inflammatory
      activities of LJEE act synergistically to accelerate wound repair.

PMID- 23173657
TI  - Models of care in nursing: a systematic review.
AB  - OBJECTIVE: This review investigated the effect of the various models of nursing
      care delivery using the diverse levels of nurses on patient and nursing outcomes.
      METHODS: All published studies that investigated patient and nursing outcomes
      were considered. Studies were included if the nursing delivery models only
      included nurses with varying skill levels. A literature search was performed
      using the following databases: Medline (1985-2011), CINAHL (1985-2011), EMBASE
      (1985 to current) and the Cochrane Controlled Studies Register (Issue 3, 2011 of
      Cochrane Library). In addition, the reference lists of relevant studies and
      conference proceedings were also scrutinised. Two reviewers independently
      assessed the eligibility of the studies for inclusion in the review, the
      methodological quality and extracted details of eligible studies. Data were
      analysed using the RevMan software (Nordic Cochrane Centre, Copenhagen, Denmark).
      RESULTS: Fourteen studies were included in this review. The results reveal that
      implementation of the team nursing model of care resulted in significantly
      decreased incidence of medication errors and adverse intravenous outcomes, as
      well as lower pain scores among patients; however, there was no effect of this
      model of care on the incidence of falls. Wards that used a hybrid model
      demonstrated significant improvement in quality of patient care, but no
      difference in incidence of pressure areas or infection rates. There were no
      significant differences in nursing outcomes relating to role clarity, job
      satisfaction and nurse absenteeism rates between any of the models of care.
      CONCLUSIONS: Based on the available evidence, a predominance of team nursing
      within the comparisons is suggestive of its popularity. Patient outcomes, nurse
      satisfaction, absenteeism and role clarity/confusion did not differ across model
      comparisons. Little benefit was found within primary nursing comparisons and the
      cost effectiveness of team nursing over other models remains debatable.
      Nonetheless, team nursing does present a better model for inexperienced staff to
      develop, a key aspect in units where skill mix or experience is diverse.

PMID- 23173658
TI  - Making evidence more wanted: a systematic review of facilitators to enhance the
      uptake of evidence from systematic reviews and meta-analyses.
AB  - CONTEXT: The increased uptake of evidence from systematic reviews is advocated
      because of their potential to improve the quality of decision making for patient
      care. Systematic reviews can do this by decreasing inappropriate clinical
      variation and quickly expediting the application of current, effective advances
      to everyday practice. However, research suggests that evidence from systematic
      reviews has not been widely adopted by health professionals. Little is known
      about the facilitators to uptake of research evidence from systematic reviews and
      meta-analyses. OBJECTIVE: To review the facilitators to the uptake by decision
      makers, of evidence from systematic, meta-analyses and the databases containing
      them. SEARCH STRATEGY: We searched 19 databases covering the full range of
      publication years, utilised three search engines and also personally contacted
      investigators. Grey literature and knowledge translation research was
      particularly sought. Reference lists of primary studies and related reviews were
      also searched. SELECTION CRITERIA: Studies were included if they reported on the
      views and perceptions of decision makers on the uptake of evidence from
      systematic reviews, meta-analyses and the databases associated with them. One
      investigator screened titles to identify candidate articles, and then two
      reviewers independently assessed the relevance of retrieved articles to exclude
      studies that did not meet the inclusion criteria. Quality of the included studies
      was also assessed. DATA EXTRACTION: Using a pre-established taxonomy, two
      reviewers described the methods of included studies and extracted data that were
      summarised in tables and then analysed. Differences were resolved by consensus.
      RESULTS: Of articles initially identified, we selected unique published studies
      describing at least one facilitator to the uptake of evidence from systematic
      reviews. The 15 unique studies reported 10 surveys, three qualitative
      investigations and two mixed studies that addressed potential facilitators. Five
      studies were from Canada, four from the UK, three from Australia, one from Iran
      and one from South-east Asia (Indonesia, Malaysia, Thailand and the Philippines),
      with one study covering both Canada and UK. In total, the 15 studies covered
      eight countries from four continents. Of 2495 participants in the 15 studies, at
      least 1343 (53.8%) were physicians. Perceived facilitators to the use of evidence
      from systematic reviews varied. The 15 studies yielded 54 potential facilitators
      to systematic review uptake. The five most commonly reported perceived
      facilitators to uptake of evidence from systematic reviews were the following:
      the perception that systematic reviews have multiple uses for improving
      knowledge, research, clinical protocols and evidence-based medicine skills
      (6/15); a content that included benefits, harms and costs and is current,
      transparent and timely (6/15); a format with a 1:3:25 staged access and executive
      summary (5/15); training in use (4/15); and peer-group support (4/15).
      CONCLUSION: The results expand our understanding of how multiple factors act as
      facilitators to optimal clinical practice. This systematic review reveals that
      interventions to foster uptake of evidence from systematic reviews, meta-analyses
      and The Cochrane Library can build on a broad range of facilitators.

PMID- 23173659
TI  - Current evidence on evidence-based practice training in allied health: a
      systematic review of the literature.
AB  - INTRODUCTION: It is essential that allied health practice decisions are
      underpinned by the best available evidence. Therefore, effective training needs
      to be provided for allied health professionals to do this. However, little is
      known about how evidence-based practice training programs for allied health
      professionals are delivered, the elements contained within them, how learning
      outcomes are measured or the effectiveness of training components in improving
      learning outcomes. METHODS: We conducted a systematic literature review to
      identify effectiveness of evidence-based practice training programs and their
      components for allied health professionals. Key words of evidence-based practice
      programs OR journal clubs OR critical appraisal AND allied health OR
      physiotherapists OR occupational therapists OR speech pathologists AND knowledge
      OR skills OR attitudes OR behaviour were applied to all available databases.
      Papers were critically appraised using the Joanna Briggs Institute and McMaster
      tools and the checklist of recommendations for educational interventions. Data
      were extracted on participants, training program components and underpinning
      theories, methods of delivery and learning outcomes. Data were synthesised using
      a combination of narrative and realist synthesis approaches. RESULTS: Six
      relevant studies (four randomised controlled trials and two before-and-after
      studies) reported on the effectiveness of evidence-based practice training
      programs for evidence-based practice for groups of health professionals.
      Specifically, only three of these studies (one randomised controlled trial and
      two before-and-after studies) reported on allied health professionals
      (physiotherapists, occupational therapists and social workers). Among these three
      studies on allied health, outcomes were variably measured, largely reporting on
      knowledge, skills, attitudes and/or behaviours. Significant changes in knowledge
      and skills were reported in all studies. Only the social work study, which
      reassessed outcomes after 3 months, reported significant changes in attitudes and
      behaviours. Training took from 3 hours to 2 days. While there was information on
      training program components, there was no evidence of effectiveness related to
      learning outcomes. CONCLUSION: Overall, there is limited research regarding
      training of allied health professionals in evidence-based practice and learning
      outcomes. From the limited evidence base, there was consistent evidence that any
      training significantly influenced knowledge, skills and attitudes, irrespective
      of the allied health discipline. There was little information, however, regarding
      how to change or measure behaviours. This review cannot recommend components of
      training for allied health professionals in evidence-based practice, which
      significantly improve learning outcomes.

PMID- 23173660
TI  - Implementation of evidence-based healthcare in Papua New Guinea.
AB  - AIM: The aim of this research was to understand how health workers in developing
      countries reach diagnostic and treatment decisions. In developing countries,
      health workers are often forced to make diagnostic and treatment decisions based
      on limited knowledge, unhelpful information, infrequent and low technology back
      up services and without the support of more senior staff. Yet patients continue
      to be treated. This paper investigates how primary healthcare workers in such
      contexts reach these diagnostic and treatment decisions. METHOD: Using a
      qualitative methodology, 58 primary healthcare workers from the three primary
      healthcare facilities in Papua New Guinea--aid posts, sub-health centres and
      health centres--participated in an in-depth interview, in order to investigate
      how diagnostic and treatment decisions were made. RESULTS: Although participants
      were originally trained in the biomedical model, they lived and worked in a
      context where other belief systems operated to diagnose and treat illness. This
      led to the coexistence of at least three models of treatment: the biomedical
      model, traditional indigenous health practices and Christian beliefs. Thus, a
      homogenous biomedical understanding of health and well-being was not possible in
      this setting, and treatment options did not always follow the biomedical
      recommendations. CONCLUSIONS: In developing countries where competing medical
      frame works exist, evidence-based practices may be more difficult to implement.
      Although the skill and knowledge of the provider and availability of treatment
      resources are still important, belief in the accuracy of the diagnosis and the
      potency of the treatment by the patient and the patient's community as well as
      the health provider may be just as significant.

PMID- 23173661
TI  - Patient handover in the oncology setting: an evidence utilisation project.
AB  - BACKGROUND: Handover is an essential activity in nursing and is an integral part
      of communication as it will improve and ensure quality patient care in clinical
      practice. However, handover could be ineffective and harmful to patients and
      nurses if the information communicated is incorrect, irrelevant or omitted. Thus
      to achieve optimal care as well as to maintain patient safety, these information
      needs to be accurately communicated. In recent time, registered nurses in the
      ward have been staying late beyond their working hours as handover is taking more
      time than is required. The nurses were taking almost an hour to hand over their
      reports to the oncoming staff. There was also a lot of distraction and
      interruption which further prolonged the time spent handing over. This has led to
      much unhappiness and dissatisfaction in the ward. In addition, it also took the
      registered nurses away from direct clinical care. AIM: The aim of this project
      was to improve the quality and duration of inter-shift patient handover from
      morning to afternoon shift. METHODS: This project utilised a pre- and post-audit
      methodology using the Joanna Briggs Institute Practical Application of Clinical
      Evidence System (JBI PACES) and Getting Research into Practice module. It was
      implemented in three phases over a 6-month period from June 2011 to December
      2011. The audit utilised four out of the six criteria recommended by Joanna
      Briggs Institute clinical handover best practice sheet. It took place in a 16-bed
      oncology ward within an acute care hospital in Singapore, involving a sample size
      of 15 registered nurses. It involved educating the registered nurses in the
      process of patients' handover with the aid of cue cards. RESULTS: All four
      Criterions achieved 100% compliance. Compliance rate among the registered nurses
      increased for Criterion 2 to Criterion 4, showing significant improvement,
      especially in Criterion 4. Fisher's exact test was carried out to determine
      statistical significance between results of the two audits. Compliance for
      Criterion 1 remained at 100%. Criterion 2 achieved 100% compliance compared with
      80% in the pre-implementation audit, highlighting an improvement of 20% (chi(2) =
      3.333, P = 0.068). Criterion 3 showed 100% compliance compared with 80% in the
      pre-implementation audit, indicating an improvement of 20% (chi(2) = 3.333, P =
      0.068). Criterion 4 now showed 100% compliance compared with 47% in the pre
      implementation audit, indicating a significant improvement of 53% (chi(2) =
      9.130, P = 0.003). CONCLUSION: This project not only showed a significant
      improvement in the inter-shift patient handover, but also shortened the duration
      of handover by 21.67 min per registered nurse. This project also showed that
      commitment, acceptance, enthusiasm and support from all the registered nurses and
      stakeholders are essential contributing factors towards the success of improving
      clinical practice. Utilising the JBI PACES approach of audit and feedback has
      helped in reducing the time spent on handover. It has demonstrated that the use
      of evidence to improve clinical practice is possible in a challenging acute care
      environment.

PMID- 23173662
TI  - Nutritional screening among patients with cancer in an acute care hospital: a
      best practice implementation project.
AB  - AIM: This project sought to improve the nutritional screening practice among
      registered nurses in caring for adult patients with cancer. METHODS: This project
      used the pre- and post-implementation audit strategy using Joanna Briggs
      Institute Practical Application of Clinical Evidence System and Getting Research
      into Practice (JBI-PACES) module. The audit, feedback and re-audit sequence was
      the strategy used to improve clinical practice. This project ran over three
      phases during a 5-month period from July to November 2011. RESULTS: This project
      utilised three criteria from the JBI-PACES. The criteria are: (i) a validated
      screening tool is used to identify patients at risk for malnutrition; (ii)
      patients are screened upon admission using a validated screening tool; and (iii)
      appropriate action plans are initiated when at-risk patients for malnutrition are
      identified. According to the pre-implementation audit, only Criterion 1 showed
      100% compliance. Criterion 2 and 3 showed 96% and 46% compliance, respectively.
      The audit team identified four barriers and developed action plans, which
      included a simplified nutritional screening tool and empowerment of the nurses
      for dietician referral. The post-implementation audit showed 100% compliance rate
      achieved for all the three criteria. CONCLUSION: This project used the pre- and
      post-audit strategy to translate evidence into practice. It demonstrated not only
      that implementation of best practice is possible in a busy oncology ward, but
      also showed a remarkable improvement in the nutritional screening of patients
      with cancer.

PMID- 23173663
TI  - Hand hygiene in the nursery during diaper changing.
AB  - AIM: This project aimed to improve hand hygiene practice during diaper changing
      among nurses working in the nursery. METHODS: This project was conducted in one
      of the nurseries in a 935-bed acute care hospital with a sample of 15 nurses. A
      pre- and post-intervention audit was conducted utilising the Joanna Briggs
      Institute Practical Application of Clinical Evidence System and Getting Research
      into Practice module. A revised written workflow, which specified the occasions
      and process for hand hygiene during diaper changing, was introduced.
      Modifications to the baby bassinets and nursery were made after barriers to good
      hand hygiene were identified. The project was carried out over 4 months, from
      March to June 2011. RESULTS: The post-intervention audit results show an
      improvement in performing hand washing after changing diapers (20%) and
      performing the correct steps of hand rubbing (25%). However, the compliance rates
      decreased for the other criteria that measured whether hand rubbing or hand
      washing was performed prior to contacting the infant and after wrapping the
      infant, and whether hand washing was performed correctly. The improvement in
      compliance with hand washing--the main focus of the new workflow--after changing
      diapers was especially significant. CONCLUSION: The results indicated that having
      a workflow on the occasions and process for hand hygiene during diaper changing
      was useful in standardising practice. Pre- and post-implementation audits were
      effective methods for evaluating the effect of translating evidence into
      practice. However, this project had limited success in improving compliance with
      hand hygiene. This suggested that more effort is needed to reinforce the
      importance of hand hygiene and compliance to the proposed workflow. In addition,
      this project showed that for change to take place successfully, environmental
      modifications, increased awareness and adequate communication to every staff
      member are essential.

PMID- 23173664
TI  - Promoting continence in nursing homes in four European countries: the use of
      PACES as a mechanism for improving the uptake of evidence-based recommendations.
AB  - BACKGROUND: Multi-faceted approaches are generally recognised as the most
      effective way to support the implementation of evidence into practice. Audit and
      feedback often constitute one element of a multi-faceted implementation package,
      alongside other strategies, such as interactive education and facilitated support
      mechanisms. This paper describes a multi-faceted implementation strategy that
      used the Joanna Briggs Institute Practical Application of Clinical Evidence
      System (PACES) as an online audit tool to support facilitators working to
      introduce evidence-based continence recommendations in nursing homes in four
      different European countries. AIMS/OBJECTIVES: The paper describes the experience
      of using PACES with an international group of nursing home facilitators. In
      particular, the objectives of the paper are: to describe the process of
      introducing PACES to internal facilitators in eight nursing homes; to discuss the
      progress made during a 12-month period of collecting and analysing audit data
      using PACES; to summarise the collective experience of using PACES, including
      reflections on its strengths and limitations. METHODS: Descriptive data were
      collected during the 12-month period of working with PACES in the eight nursing
      home sites. These data included digital and written notes taken at an initial 3
      day introductory programme, at monthly teleconferences held between the external
      and internal facilitators and at a final 2-day meeting. Qualitative analysis of
      the data was undertaken on an ongoing basis throughout the implementation period,
      which enabled formative evaluation of PACES. A final summative evaluation of the
      experience of using PACES was undertaken as part of the closing project meeting
      in June 2011. RESULTS: The nursing home facilitators took longer than anticipated
      to introduce PACES and it was only after 9-10 months that they became confident
      and comfortable using the system. This was due to a combination of factors,
      including a lack of audit knowledge and skills, limited IT access and skills,
      language difficulties and problems with the PACES system itself. The initial plan
      of undertaking a full baseline audit followed by focused action cycles had to be
      revised to allow a more staged, smaller-scale approach to implementation and
      audit. This involved simplifying the audit process and removing steps such as the
      calculation of population size estimates. As a result, an accurate baseline
      measure, prior to introducing changes to continence care, was not achieved.
      However, by the end of the 12 months, the majority of facilitators had undertaken
      a full audit and reported value in the process. In particular, they benefited
      from comparing audit data across sites to share learning and best practice.
      DISCUSSION/CONCLUSION: Working with PACES as part of a facilitated programme to
      support the implementation of evidence-based continence recommendations in
      nursing homes in four European countries has been a valuable learning experience,
      although not without its challenges. The findings highlight the importance of
      thorough training and support for first time users of PACES and the need to make
      the audit process as simple as possible in the initial stages.

PMID- 23173665
TI  - What is a rapid review? A methodological exploration of rapid reviews in Health
      Technology Assessments.
AB  - AIM: Commissioners of Health Technology Assessments require timely reviews to
      attain efficacious decisions on healthcare and treatments. In recent years, there
      has been an emergence of 'rapid reviews' within Health Technology Assessments;
      however, there is no known published guidance or agreed methodology within
      recognised systematic review or Health Technology Assessment guidelines. In order
      to answer the research question 'What is a rapid review and is methodology
      consistent in rapid reviews of Health Technology Assessments?', a study was
      undertaken in a sample of rapid review Health Technology Assessments from the
      Health Technology Assessment database within the Cochrane Library and other
      specialised Health Technology Assessment databases to investigate similarities
      and/or differences in rapid review methodology utilised. METHOD: In a targeted
      search to obtain a manageable sample of rapid reviews, the Health Technology
      Assessment database of The Cochrane Library and six international Health
      Technology Assessment databases were searched to locate rapid review Health
      Technology Assessments from 2000 onwards. Each rapid review was examined to
      investigate the individual methodology used for searching, inclusion screening,
      quality assessment, data extraction and synthesis. Methods of each rapid review
      were compared to investigate differences and/or similarities in methodologies
      used, in comparison with recognised methods for systematic reviews. RESULTS:
      Forty-six full rapid reviews and three extractable summaries of rapid reviews
      were included. There was a wide diversity of methodology, with some reviews
      utilising well-established systematic review methods, but many others
      diversifying in one or more areas, that is searching, inclusion screening,
      quality assessment, data extraction, synthesis methods, report structure and
      number of reviewers. There was a significant positive correlation between the
      number of recommended review methodologies utilised and length of time taken in
      months. CONCLUSIONS: Despite the number of rapid reviews published within Health
      Technology Assessments over recent years, there is no agreed and tested
      methodology and it is unclear how rapid reviews differ from systematic reviews.
      In a sample of Health Technology Assessment rapid reviews from 2000 to 2011,
      there was a wide diversity of methodology utilised in all aspects of rapid
      reviews. There is scope for wider research in this area to investigate the
      diversity of methods in more depth during each stage of the rapid review process,
      so that eventually recommendations could be made for clear and systematic methods
      for rapid reviews, thus facilitating equity and credibility of this type of
      important review methodology.

PMID- 23173671
TI  - MicroRNA-99a induces G1-phase cell cycle arrest and suppresses tumorigenicity in
      renal cell carcinoma.
AB  - BACKGROUND: A growing body of evidence suggests that microRNAs (miRNAs) play an
      important role in cancer diagnosis and therapy. MicroRNA-99a (miR-99a), a
      potential tumor suppressor, is downregulated in several human malignancies. The
      expression and function of miR-99a, however, have not been investigated in human
      renal cell carcinoma (RCC) so far. We therefore examined the expression of miR
      99a in RCC cell lines and tissues, and assessed the impact of miR-99a on the
      tumorigenesis of RCC. METHODS: MiR-99a levels in 40 pairs of RCC and matched
      adjacent non-tumor tissues were assessed by real-time quantitative Reverse
      Transcription PCR (qRT-PCR). The RCC cell lines 786-O and OS-RC-2 were
      transfected with miR-99a mimics to restore the expression of miR-99a. The effects
      of miR-99a were then assessed by cell proliferation, cell cycle, transwell, and
      colony formation assay. A murine xenograft model of RCC was used to confirm the
      effect of miR-99a on tumorigenicity in vivo. Potential target genes were
      identified by western blotting and luciferase reporter assay. RESULTS: We found
      that miR-99a was remarkably downregulated in RCC and low expression level of miR
      99a was correlated with poor survival of RCC patients. Restoration of miR-99a
      dramatically suppressed RCC cells growth, clonability, migration and invasion as
      well as induced G1-phase cell cycle arrest in vitro. Moreover, intratumoral
      delivery of miR-99a could inhibit tumor growth in murine xenograft models of
      human RCC. In addition, we also fond that mammalian target of rapamycin (mTOR)
      was a direct target of miR-99a in RCC cells. Furthermore, siRNA-mediated
      knockdown of mTOR partially phenocopied the effect of miR-99a overexpression,
      suggesting that the tumor suppressive role of miR-99a may be mediated primarily
      through mTOR regulation. CONCLUSIONS: Collectively, these results demonstrate for
      the first time, to our knowledge, that deregulation of miR-99a is involved in the
      etiology of RCC partially via direct targeting mTOR pathway, which suggests that
      miR-99a may offer an attractive new target for diagnostic and therapeutic
      intervention in RCC.

PMID- 23173670
TI  - Potential role of probiotics on colorectal cancer prevention.
AB  - BACKGROUND: Colorectal cancer represents the most common malignancy of the
      gastrointestinal tract. Owing to differences in dietary habits and lifestyle,
      this neoplasm is more common in industrialized countries than in developing ones.
      Evidence from a wide range of sources supports the assumption that the link
      between diet and colorectal cancer may be due to an imbalance of the intestinal
      microflora. DISCUSSION: Probiotic bacteria are live microorganisms that, when
      administered in adequate amounts, confer a healthy benefit on the host, and they
      have been investigated for their protective anti-tumor effects. In vivo and
      molecular studies have displayed encouraging findings that support a role of
      probiotics in colorectal cancer prevention. SUMMARY: Several mechanisms could
      explain the preventive action of probiotics against colorectal cancer onset. They
      include: alteration of the intestinal microflora; inactivation of cancerogenic
      compounds; competition with putrefactive and pathogenic microbiota; improvement
      of the host's immune response; anti-proliferative effects via regulation of
      apoptosis and cell differentiation; fermentation of undigested food; inhibition
      of tyrosine kinase signaling pathways.

PMID- 23173673
TI  - Two new Penicillium species Penicillium buchwaldii and Penicillium spathulatum,
      producing the anticancer compound asperphenamate.
AB  - Penicillium buchwaldii sp. nov. (type strain CBS 117181(T)  = IBT 6005(T)  = IMI
      30428(T) ) and Penicillium spathulatum sp. nov. (CBS 117192(T)  = IBT 22220(T) )
      are described as new species based on a polyphasic taxonomic approach. Isolates
      of P. buchwaldii typically have terverticillate conidiophores with echinulate
      thick-walled conidia and produce the extrolites asperphenamate,
      citreoisocoumarin, communesin A and B, asperentin and 5'-hydroxy-asperentin.
      Penicillium spathulatum is unique in having restricted colonies on Czapek yeast
      agar (CYA) with an olive grey reverse, good growth on CYA supplemented with 5%
      NaCl, terverticillate bi- and ter-ramulate conidiophores and consistently
      produces the extrolites benzomalvin A and D and asperphenamate. The two new
      species belong to Penicillium section Brevicompacta and are phylogenetically
      closely related to Penicillium tularense. With exception of Penicillium
      fennelliae, asperphenamate is also produced by all other species in section
      Brevicompacta (P. tularense, Penicillium brevicompactum, Penicillium
      bialowiezense, Penicillium olsonii, Penicillium astrolabium and Penicillium
      neocrassum). Both new species have a worldwide distribution. The new species were
      mainly isolated from indoor environments and food and feedstuffs. The fact that
      asperphenamate has been found in many widely different plants may indicate that
      endophytic fungi rather than the plants are the actual producers.

PMID- 23173672
TI  - Identification of novel genes involved in DNA damage response by screening a
      genome-wide Schizosaccharomyces pombe deletion library.
AB  - BACKGROUND: DNA damage response (DDR) plays pivotal roles in maintaining genome
      integrity and stability. An effective DDR requires the involvement of hundreds of
      genes that compose a complicated network. Because DDR is highly conserved in
      evolution, studies in lower eukaryotes can provide valuable information to
      elucidate the mechanism in higher organisms. Fission yeast (Schizosaccharomyces
      pombe) has emerged as an excellent model for DDR research in recent years. To
      identify novel genes involved in DDR, we screened a genome-wide S. pombe haploid
      deletion library against six different DNA damage reagents. The library covered
      90.5% of the nonessential genes of S. pombe. RESULTS: We have identified 52 genes
      that were actively involved in DDR. Among the 52 genes, 20 genes were linked to
      DDR for the first time. Flow cytometry analysis of the repair defective mutants
      revealed that most of them exhibited a defect in cell cycle progression, and some
      caused genome instability. Microarray analysis and genetic complementation assays
      were carried out to characterize 6 of the novel DDR genes in more detail. Data
      suggested that SPBC2A9.02 and SPAC27D7.08c were required for efficient DNA
      replication initiation because they interacted genetically with DNA replication
      initiation proteins Abp1 and Abp2. In addition, deletion of sgf73+, meu29+,
      sec65+ or pab1+ caused improper cytokinesis and DNA re-replication, which
      contributed to the diploidization in the mutants. CONCLUSIONS: A genome-wide
      screen of genes involved in DDR emphasized the key role of cell cycle control in
      the DDR network. Characterization of novel genes identified in the screen helps
      to elucidate the mechanism of the DDR network and provides valuable clues for
      understanding genome stability in higher eukaryotes.

PMID- 23173674
TI  - Genotyping of Plasmodium falciparum using antigenic polymorphic markers and to
      study anti-malarial drug resistance markers in malaria endemic areas of
      Bangladesh.
AB  - BACKGROUND: In the past many regions of Bangladesh were hyperendemic for malaria.
      Malaria control in the 1960s to 1970s eliminated malaria from the plains but in
      the Chittagong Hill Tracts remained a difficult to control reservoir. The
      Chittagong Hill Tracts have areas with between 1 and 10% annual malaria rates,
      predominately 90-95% Plasmodium falciparum. In Southeast Asia, multiplicity of
      infection for hypo-endemic regions has been approximately 1.5. Few studies on the
      genetic diversity of P. falciparum have been performed in Bangladesh. Anderson et
      al. performed a study in Khagrachari, northern Chittagong Hill Tracts in 2002 on
      203 patients and found that parasites had a multiplicity of infection of 1.3 by
      MSP-1, MSP-2 and GLURP genotyping. A total of 94% of the isolates had the K76T
      Pfcrt chloroquine resistant genotype, and 70% showed the N86Y Pfmdr1 genotype.
      Antifolate drug resistant genotypes were high with 99% and 73% of parasites
      having two or more mutations at the dhfr or dhps loci. METHODS: Nested and real
      time polymerase chain reaction (PCR) methods were used to genotype P. falciparum
      using antigenic polymorphic markers and to study anti-malarial drug resistance
      markers in malaria endemic areas of Bangladesh. RESULTS: The analysis of
      polymorphic and drug resistant genotype on 33 paired recrudescent infections
      after drug treatment in the period 2004 to 2008 in the Chittagong Hill Tracts,
      which is just prior to countrywide provision of artemisinin combination therapy.
      Overall the multiplicity of infection for MSP-1 was 2.7 with a slightly smaller
      parasite diversity post-treatment. The 13 monoclonal infections by both GLURP and
      MSP-1 were evenly divided between pre- and post-treatment. The MSP-1 MAD block
      was most frequent in 66 of the samples. The prevalence of the K76T PfCRT
      chloroquine resistant allele was approximately 82% of the samples, while the
      resistant Pfmdr1 N86Y was present in 33% of the samples. Interestingly, the post
      treatment samples had a small but significantly higher frequency of the sensitive
      PfCRT alleles by RT-PCR. CONCLUSION: The parasite population retains high
      population diversity despite hypo-endemic transmission with retention, but
      decrease in the chloroquine-resistant allele and Pfmdr1 resistant alleles in the
      Chittagong Hill Tracts of Bangladesh.

PMID- 23173675
TI  - Quantitative reduction of peripheral CD4+ CD25+ FOXP3+ regulatory T cells in
      reproductive failure after artificial insemination by donor sperm.
AB  - PROBLEM: The objective of this study was to determine whether peripheral Treg
      cell percentages were altered in women with reproductive failure after artificial
      insemination by donor sperm (AID) and which parameters can best discriminate
      women with AID failure and normal controls. METHOD OF STUDY: A retrospective case
      control study of 20 fertile controls and 20 patients undergoing more than four
      treatment cycles with negative pregnancy test (Group I), 20 experiencing
      biochemical pregnancy loss (Group II), and 20 undergoing missed abortion or
      spontaneous miscarriage (Group III) was performed. The peripheral percentages of
      CD4(+) CD25(+)  and CD4(+) CD25 (+) Foxp3(+)  Treg cells within CD4(+)  T-cell
      population were evaluated at both late follicular and luteal phases of menstrual
      cycle by flow cytometry. RESULTS: A significantly decreased percentage of CD4(+)
      CD25(+) Foxp3(+)  Treg cells was detected at the late follicular phase in all AID
      failure groups compared with the controls. The percentage of CD4(+) CD25(+)
      Foxp3(+)  Treg cells at the late follicular phase in the controls was higher than
      that at the luteal phase. Using receiver operating characteristic curve, we found
      that CD4(+) CD25(+) Foxp3(+)  Treg-cell percentage <2% can best discriminate the
      AID failure and normal controls. CONCLUSION: Reduced percentage of peripheral
      CD4(+) CD25(+)  Foxp3(+)  Treg cells at the late follicular phase was associated
      with AID failure and can be a potential biomarker for predicting AID-induced
      failure.

PMID- 23173676
TI  - Comparative efficacy of three brands of gum acacia on adenine-induced chronic
      renal failure in rats.
AB  - Gum acacia (GA) is used in pharmaceutical, cosmetic and food industries as an
      emulsifier and stabilizer, and in some countries in the traditional treatment of
      patients with chronic kidney disease (CKD). We have previously found that GA
      ameliorates adenine-induced chronic renal failure (CRF) in rats. Different brands
      of GA are commercially available, but their comparative efficacy against adenine
      induced CKD is unknown. Here, we explored the effects of three different brands
      of GA (Sudanese GA, Supergum and GA from BDH) on some physiological, biochemical,
      and histological effects of adenine-induced CRF in rats. Adenine (0.75 %, w/w in
      feed, four weeks) reduced body weight, and increased urine output. It also
      induced significant increases in blood pressure, and in creatinine, urea, several
      inflammatory cytokines in plasma, and indices of oxidative stress, and caused
      histological damage in kidneys. Treatment of rats concomitantly with any of the
      three GA brands, significantly, and to a broadly similar extent, mitigated all
      the signs of CRF. The results suggested equivalent efficacy of these brands in
      antagonizing the CRF in this animal model. However, to enable standardization of
      different brands between laboratories, the use of the chemically well
      characterized GA preparation (such as Supergum) is recommended.

PMID- 23173677
TI  - Aprotinin reduces the procalcitonin rise associated with complex cardiac surgery
      and cardiopulmonary bypass.
AB  - Aprotinin, a nonspecific serine protease inhibitor, has been primarily used as a
      haemostatic drug in cardiac surgery with cardio-pulmonary bypass (CPB). This
      study investigated the effect of aprotinin on the post-operative levels of
      procalcitonin (PCT) and a set of cytokines in patients undergoing pulmonary
      artery endarterectomy (PEA). We analyzed 60 patients with chronic thromboembolic
      pulmonary hypertension undergoing PEA. 30 patients (Group A) were treated with
      aprotinin (2,00,00 IU prior anesthesia, then 2,00,00 IU in CPB prime and 50,00 IU
      per hour continuously); a further 30 patients (Group B) received tranexamic Acid
      (1 g before anesthesia, 1 g after full heparin dose and 2 g in CPB prime). PCT,
      TNFalpha, IL-1beta, IL-6, and IL-8 arterial concentrations were measured from
      before until 72 hours after surgery. Aprotinin significantly affected early post
      PEA plasma PCT. Patients treated with aprotinin (Group A) had lower peak PCT
      levels compared to patients in Group B (1.52 ng/ml versus 2.18, p=0.024).
      Postoperative peak values of PCT and IL-6 correlated closely in both groups
      (r=0.78, r=0.83 respectively). Aprotinin attenuates the post-PEA increase of PCT
      in the same manner as other pro-inflammatory cytokines. Significant correlation
      between PCT and IL-6 post-surgery may be indicative of an indirect IL-6-mediated
      pathway of PCT alteration.

PMID- 23173678
TI  - Effects of smoking cessation on hormonal levels in men.
AB  - Chronic smoking can cause imbalance in endocrine homeostasis and impairment of
      fertility in both sexes. The male reproductive system is more resilient, still
      the literature provides conflicting results about the influence of smoking on the
      steroid hormone levels. The data about smoking cessation are limited; there has
      not yet been a study primarily focused on changes in steroids levels. In our
      study, we analyzed levels of testosterone, dehydroepiandrosterone (DHEA),
      dehydroepiandrosterone sulphate (DHEAS), cortisol and sex hormone-binding
      globulin (SHBG) in male smokers and during smoking cessation. Monitored analytes
      were determined by RIA. The free testosterone index was calculated. Basal samples
      of men successful and unsuccessful in smoking cessation did not differ and
      monitored hormones could hardly predict success of smoking cessation. After one
      year without smoking, a significant BMI increase and SHBG decrease in former
      smokers was observed. The decrease in total testosterone was non-significant.
      Changes in SHBG and testosterone did not correlate with BMI, presumably due to
      the direct effect of smoking cessation.

PMID- 23173679
TI  - Chronic inflammation and low-dose glucocorticoid effects on glucose metabolism in
      premenopausal females with rheumatoid arthritis free of conventional metabolic
      risk factors.
AB  - Chronic systemic inflammation is associated with increased cardiovascular
      mortality in patients with rheumatoid arthritis (RA). The aim of our study was to
      investigate association of glucose metabolism and inflammatory markers in a group
      of patients with rheumatoid arthritis free of other metabolic risk factors.
      Twenty-two premenopausal RA females (11 patients on low-dose GC (<8.5 mg/day of
      prednisone or equivalent), 11 patients without glucocorticoid therapy) and 15 age
      and BMI-matched healthy females underwent the oral glucose tolerance test. The
      insulin sensitivity indices according Matsuda (ISI(MAT)) and Cederholm (ISI(CED))
      as well as HOMA2 %S were calculated. Cytokines, lipid profile, non-esterified
      fatty acids (NEFA) and plasminogen activator inhibitor-1 (PAI-1) were measured in
      baseline blood samples. Despite elevated interleukin IL-6 and TNF alpha, glucose,
      insulin and C-peptide responses to oral glucose load as well as ISI(MAT),
      ISI(CED), PAI-1 and NEFA were comparable in both RA groups and healthy controls.
      HOMA2 %S correlated with disease activity. In conclusions, low-dose
      glucocorticoid treatment does not lead to glucose metabolism impairment in RA
      patients without other metabolic risk factors. Increased cardiovascular mortality
      and morbidity is probably due to a direct effect of systemic inflammation on
      myocardium and/or blood vessels.

PMID- 23173680
TI  - Temporal and spatial expression of podocyte-associated molecules are accompanied
      by proteinuria in IgA nephropathy rat model.
AB  - We used a rat model to assess the role of nephrin, podocin, and desmin in the
      pathogenesis of IgA nephropathy (IgAN). A rat IgAN model was established by
      administration of BSA, CCl(4), and lipopolysaccharide (LPS) and compared with
      healthy control rats. Urinary protein, urine red blood cells, and biochemical
      parameters were measured for 12 weeks. Renal morphology and ultrastructure were
      examined by light and electron microscopy. Immunofluorescence was used to assess
      IgA deposition in the glomeruli and to measure expression of nephrin, podocin,
      and desmin. Real-time quantitative PCR was used to measure expression of nephrin,
      podocin, and desmin mRNAs. IgAN rats developed proteinuria at week-6 and this
      worsened over time. Pathological changes were evident under light microscopy at
      week-8 and under electron microscopy at week-4. Immunofluorescence analysis
      showed deposition of IgA in the kidneys of IgAN rats, but not control rats. IgAN
      rats had increased expression of glomerular podocin, nephrin, and desmin mRNAs
      and proteins at week-4. The expression of nephrin, podocin and desmin proteins
      and the expression of podocin and desmin mRNAs preceded the increase in urinary
      protein. Taken together, our study of a rat model of IgAN indicates that changes
      in the expression and distribution of nephrin, podocin, and desmin precede and
      may cause foot process fusion and proteinuria.

PMID- 23173681
TI  - Heterologous expression of a glial Kir channel (KCNJ10) in a neuroblastoma spinal
      cord (NSC-34) cell line.
AB  - Heterologous expression of Kir channels offers a tool to modulate excitability of
      neurons which provide insight into Kir channel functions in general. Inwardly
      rectifying K+ channels (Kir channels) are potential candidate proteins to
      hyperpolarize neuronal cell membranes. However, heterologous expression of
      inwardly-rectifying K+ channels has previously proven to be difficult. This was
      mainly due to a high toxicity of the respective Kir channel expression. We
      investigated the putative role of a predominantly glial-expressed, weakly
      rectifying Kir channel (Kir4.1 channel subunit; KCNJ10) in modulating
      electrophysiological properties of a motoneuron-like cell culture (NSC-34).
      Transfection procedures using an EGFP-tagged Kir4.1 protein in this study proved
      to have no toxic effects on NSC-34 cells. Using whole cell-voltage clamp, a
      substantial increase of inward rectifying K+ currents as well as
      hyperpolarization of the cell membrane was observed in Kir4.1-transfected cells.
      Na+ inward currents, observed in NSC-34 controls, were absent in Kir4.1/EGFP
      motoneuronal cells. The Kir4.1-transfection did not influence the NaV1.6 sodium
      channel expression. This study demonstrates the general feasibility of a
      heterologous expression of a weakly inward-rectifying K+ channel (Kir4.1 subunit)
      and shows that in vitro overexpression of Kir4.1 shifts electrophysiological
      properties of neuronal cells to a more glial-like phenotype and may therefore be
      a candidate tool to dampen excitability of neurons in experimental paradigms.

PMID- 23173682
TI  - Impacts of perinatal induced photothrombotic stroke on sensorimotor performance
      in adult rats.
AB  - Perinatal ischemic stroke is a leading cerebrovascular disorder occurring in
      infants around the time of birth associated with long term comorbidities
      including motor, cognitive and behavioral deficits. We sought to determine the
      impact of perinatal induced stroke on locomotion, behavior and motor function in
      rats. A photothrombotic model of ischemic stroke was used in rat at postnatal day
      7. Presently, we induced two lesions of different extents, to assess the
      consequences of stroke on motor function, locomotion and possible correlations to
      morphological changes. Behavioral tests sensitive to sensorimotor changes were
      used; locomotion expressed as distance moved in the open field was monitored and
      histological changes were also assessed. Outcomes depicted two kinds of lesions
      of different shapes and sizes, relative to laser illumination. Motor performance
      of rats submitted to stroke was poor when compared to controls; a difference in
      motor performance was also noted between rats with small and large lesions.
      Correlations were observed between: motor performance and exposition time; volume
      ratio and exposition time; and in the rotarod between motor performance and
      volume ratio. Outcomes demonstrate that photothrombotic cerebral ischemic stroke
      induced in early postnatal period and tested in adulthood, indeed influenced
      functional performance governed by the affected brain regions.

PMID- 23173683
TI  - Hindlimb suspension does not influence mechanical sensitivity, epidermal
      thickness, and peripheral nerve density in the glabrous skin of the rat hind paw.
AB  - Our aim was to investigate the influence of microgravity on the sensitivity of
      the skin to mechanical stimulation, epidermal thickness, peripheral nerve density
      in the upper dermis, and serum levels of a stress marker in a rat hindlimb
      suspension (HS) model. Thirty 8-week-old male Wistar rats were randomly divided
      into 3 groups: HS, n=10; sham HS, n=10; control, n=10. The suspension system was
      attached to rat tails in both the HS and sham-HS groups, but the hindlimbs were
      suspended only in the HS group. The HS and sham-HS groups were treated for 4
      weeks. In behavioral tests using von-Frey filaments (n=5 in each group),
      mechanical hypersensitivity developed in the HS and sham HS groups. Serum
      corticosterone levels increased significantly in the HS and sham HS groups
      compared to the control group, and no changes in epidermal thickness or
      peripheral nerve density were observed immediately after the removal of HS (n=5
      in each group). These data indicated that the mechanical hypersensitivity
      observed in the HS group was not caused by microgravity or inactivity, but rather
      by restraint stress. We suggest that microgravity does not affect skin
      sensitivity and histology in these animals. Unit of Physical Therapy and
      Occupational Therapy Sciences, Nagasaki University Graduate School of Biochemical
      Sciences, Nagasaki-shi, Japan.

PMID- 23173684
TI  - Collagenolytic potential of rat liver myofibroblasts.
AB  - Rat liver myofibroblasts (MFB) were isolated by repeated passaging of
      nonparenchymal liver cell fraction. They were cultured on polystyrene Petri
      dishes, on fibrin or on type I collagen gels for 5 days. Quantitative RT-PCR,
      Western blotting, zymography and immunocytochemistry were used to study
      differences in cell morphology and protein expression. MFB were large and spread
      on plastic substrate, with prominent alpha-smooth muscle (alpha-SMA) fibres. They
      turned much smaller and elongated on collagen which was accompanied by the
      rearrangement of the cytoskeleton and a decrease in alpha-SMA and beta-actin
      content. Collagen gel induced the expression of a group of metalloproteinases
      (MMP-2, -3, -9, -13), on mRNA and protein level which resulted in the degradation
      of the gel. This response was accompanied by changes in the mRNA expression of
      cytokines of TGF-beta family, CTGF and interleukin-6, as well as of osteopontin
      and thrombospondin-2 that are involved in metalloproteinases (MMPs) regulation.
      The expression of MMPs substrates, collagen types I, IV and XII did not change or
      decreased. The effects of fibrin gels on MFB were milder than those of collagen.
      MFB assumed to deposit collagen and other ECM components in fibrotic liver,
      besides hepatic stellate cells, also possess a great collagenolytic potential.

PMID- 23173685
TI  - Sex differences in ICR mice in the Morris water maze task.
AB  - The Morris water maze (MWM) is one of the most common tasks used to assess
      spatial learning and memory ability in rodents. Genetic strain and gender are two
      prominent variants that influence spatial performance. Although it was reported
      that ICR (Institute of Cancer Research) mice exhibited an unchanged baseline
      performance in the training phase of the MWM task, this outbred strain has been
      widely used in learning and memory studies, and little is known regarding the
      effects of sex on behavioral performance. In this study, we demonstrated that
      both male and female ICR mice could complete the MWM task. Furthermore, a
      significant sex difference was observed, with females having shorter escape
      latencies and longer durations in the target quadrant in both the acquisition and
      test phases. Our findings emphasize the necessity of careful examination of not
      only the strain effect on behavioral performance but also the sex effect.

PMID- 23173686
TI  - Resveratrol and related compounds as antioxidants with an allosteric mechanism of
      action in epigenetic drug targets.
AB  - The present review is intended to focus on naturally occurring cytoprotective
      agents such as resveratrol (trans-3,4',5-trihydroxystilbene) and other related
      compounds, probably with similar molecular mechanisms of action and high capacity
      to find applications in medical fields. Several physiological aspects have been
      ascribed to resveratrol and similar compounds. Resveratrol, among others, has
      been recently described as a silent information regulator T1 (SIRT1) activator
      that increases AMP-activated protein kinase (AMPK) phosphorylation and reduces
      the oxidative damage biomarkers during aging in laboratory settings. The reports
      on resveratrol and other SIRT1 activators from various sources are encouraging.
      The pharmacological strategies for modulation of sirtuins by small molecules
      through allosteric mechanisms should gain a greater momentum including human
      research. Resveratrol and resveratrol-like molecules seem to fulfill the
      requirement of a new horizon in drug research since these molecules cover a
      growing research means as antioxidants with allosteric mechanism in epigenetic
      drug targets. However, one should keep in mind the challenges of extrapolation of
      basic research into clinical results. Overall, the issue of sirtuins in biology
      and disease provides an insight on therapeutic potentials of sirtuin-based
      therapeutics and demonstrates the high complexity of drug-targeting these
      modalities for human applications.

PMID- 23173687
TI  - Suppression of streptozotocin-induced type-1 diabetes in mice by radon
      inhalation.
AB  - We examined the protective effect of radon inhalation on streptozotocin (STZ)
      induced type-1 diabetes in mice. Mice inhaled radon at concentrations of 1000,
      2500, and 5500 Bq/m3 for 24 hours before STZ administration. STZ administration
      induced characteristics of type-1 diabetes such as hyperglycemia and
      hypoinsulinemia; however, radon inhalation at doses of 1000 and 5500 Bq/m3
      significantly suppressed the elevation of blood glucose in diabetic mice. Serum
      insulin was significantly higher in mice pre-treated with radon at a dose of 1000
      Bq/m3 than in mice treated with a sham. In addition, superoxide dismutase
      activities and total glutathione contents were significantly higher and lipid
      peroxide was significantly lower in mice pre-treated with radon at doses of 1000
      and 5500 Bq/m3 than in mice treated with a sham. These results were consistent
      with the result that radon inhalation at 1000 and 5500 Bq/m3 suppressed
      hyperglycemia. These findings suggested that radon inhalation suppressed STZ
      induced type-1 diabetes through the enhancement of antioxidative functions in the
      pancreas.

PMID- 23173688
TI  - New nanostructural biomaterials based on active silicate systems and
      hydroxyapatite: characterization and genotoxicity in human peripheral blood
      lymphocytes.
AB  - AIM: To characterize and investigate the genotoxic effect of a new endodontic
      cement based on dicalcium- and tricalcium-silicate (CS) with hydroxyapatite (HA)
      on human lymphocytes. METHODOLOGY: Hydrothermal treatment was applied for
      synthesis of CS and HA. The final mixture HA-CS, with potential to be used in
      endodontic practice, is composed of CS (34%) and HA (66%). Human lymphocytes were
      incubated with HA, HA-CS and CS for 1 h, at 37  degrees C and 5% CO2. Cell
      viability was determined using the trypan blue exclusion assay. To evaluate the
      level of DNA damage comet assay (single cell gel electrophoresis) was performed.
      For the statistical analysis anova and Duncan's Post Hoc Test were used. RESULTS:
      The SEM analysis indicated that CS consisted mostly of agglomerates of several
      micrometers in size, built up from smaller particles, with dimensions between 117
      and 477 nm. This is promising because dimensions of agglomerates are not
      comparable with channels inside the cell membranes, whereas their nano-elements
      provide evident activity, important for faster setting of these mixtures compared
      to MTA. Values of DNA damage obtained in the comet assay indicated low genotoxic
      risk of the new endodontic materials. CONCLUSIONS: The significantly improved
      setting characteristics and low genotoxic risk of the new material support
      further research.

PMID- 23173689
TI  - Quality of life of people with mental health problems: a synthesis of qualitative
      research.
AB  - PURPOSE: To identify the domains of quality of life important to people with
      mental health problems. METHOD: A systematic review of qualitative research
      undertaken with people with mental health problems using a framework synthesis.
      RESULTS: We identified six domains: well-being and ill-being; control, autonomy
      and choice; self-perception; belonging; activity; and hope and hopelessness.
      Firstly, symptoms or 'ill-being' were an intrinsic aspect of quality of life for
      people with severe mental health problems. Additionally, a good quality of life
      was characterised by the feeling of being in control (particularly of distressing
      symptoms), autonomy and choice; a positive self-image; a sense of belonging;
      engagement in meaningful and enjoyable activities; and feelings of hope and
      optimism. Conversely, a poor quality life, often experienced by those with severe
      mental health difficulties, was characterized by feelings of distress; lack of
      control, choice and autonomy; low self-esteem and confidence; a sense of not
      being part of society; diminished activity; and a sense of hopelessness and
      demoralization. CONCLUSIONS: Generic measures fail to address the complexity of
      quality of life measurement and the broad range of domains important to people
      with mental health problems.

PMID- 23173690
TI  - Phenomenology, psychiatric comorbidity and family history in referred preschool
      children with obsessive-compulsive disorder.
AB  - OBJECTIVE: The study aimed to investigate phenomenology, psychiatric
      comorbidity, and family history of obsessive-compulsive disorder (OCD) in a
      clinical sample of normally developing preschool children with OCD. METHOD:
      Subjects in this study were recruited from a clinical sample of preschool
      children (under 72 months of age) who were referred to a university clinic.
      Subjects with a normal developmental history and significant impairment related
      to OCD symptoms were included in the study. Children's Yale-Brown Obsessive
      Compulsive Scale was used to assess OCD symptoms. Each subject was assessed for
      comorbid DSM-IV psychiatric disorders using a semi-structured interview. Parents
      were evaluated for lifetime history of OCD in individual sessions. RESULTS:
      Fifteen boys and ten girls (age range: 28 to 69 months; 54.12+/-9.08 months) were
      included. Mean age of onset of OCD was 35.64+/-13.42 months. All subjects
      received at least one comorbid diagnosis. The most frequent comorbid disorders
      were non-OCD anxiety disorders (n=17; 68.0%), attention-deficit hyperactivity
      disorder (ADHD) (n=15; 60.0%), oppositional defiant disorder (ODD) (n=12; 48.0%),
      and tic disorders (n=6; 24.0%). Mean number of comorbid disorders was 3.65 and
      2.35 for boys and girls, respectively. At least one parent received lifetime OCD
      diagnosis in 68 percent of the subjects. CONCLUSIONS: The results indicated that
      OCD in referred preschool children is more common in males, highly comorbid with
      other psychiatric disorders, and associated with high rates of family history of
      OCD. Given the high rates of comorbidity and family history, OCD should be
      considered in referred preschool children with disruptive behavior disorders
      and/or with family history of OCD.

PMID- 23173691
TI  - Cost analysis in favor of a combined approach for cytomegalovirus after kidney
      transplantation: a single-center experience.
AB  - BACKGROUND: In kidney transplant recipients, cytomegalovirus (CMV) can cause
      significant morbidity, mortality, and costs, which can be prevented by universal
      antiviral prophylaxis or preemptive therapy. METHODS: With the aim to improve our
      understanding of the advantages and disadvantages of these interventions, we
      documented resource use for 101 consecutive kidney transplant recipients in our
      center receiving preemptive therapy and estimated resource use for 2 alternative
      scenarios. RESULTS: At 100 days after transplantation, the mean total costs of
      our preemptive strategy including monitoring and treatment with intravenous
      ganciclovir was ?2545 per patient. At ?4853 per patient, these costs were highest
      for the CMV-positive donor/CMV-negative recipient (D+/R-) patient subgroup (n =
      28), who frequently require recurrent treatment. A treatment scenario with
      valganciclovir prophylaxis for D+/R- and R+ patients, in which we ignored late
      onset disease after discontinuation of prophylaxis, resulted in an estimated cost
      of ?1892 per patient. A combined approach using valganciclovir prophylaxis in the
      D+/R- group and a preemptive strategy in the R+ groups would result in the lowest
      mean and median costs per patient (?1701). CONCLUSION: Our study suggests that a
      combined approach, using valganciclovir prophylaxis in D+/R- patients and
      preemptive treatment in R+ patients, may result in the lowest cost. This approach
      seems reasonable as it restricts expensive prophylactic drug therapy to those who
      would benefit the most, whereas it limits the risk for drug toxicity and late
      onset disease in those at lower risk for CMV.

PMID- 23173692
TI  - VEGF-dependent continuous angiogenesis in the median eminence of adult mice.
AB  - Brain vasculature forms the blood-brain barrier (BBB) that restricts the movement
      of molecules between the brain and blood, but the capillary of the median
      eminence (ME) lacks the BBB for secretion of adenohypophysial hormone-releasing
      peptides. In the present study, we aimed to elucidate whether continuous
      angiogenesis occurs in the ME of adult mice. By using a mitotic marker,
      bromodeoxyuridine (BrdU), we demonstrated that new endothelial cells were born
      continuously in the ME of adults. Prominent expression of NG2, platelet-derived
      growth factor receptor B (PDGFRB), and delta-like ligand 4 was observed at
      pericytes of adults, although the expression of these angiogenesis-associated
      proteins has been shown to be at low or trace levels in adult mature capillary.
      In addition, vascular endothelial growth factor (VEGF), a key regulator of
      angiogenesis, was expressed highly in the nervous parenchyma of the ME.
      Expression of VEGF receptor 2 (VEGFR2) was observed at endothelial cells in the
      external zone and at somatodendrites in the internal zone. Finally, a VEGFR- and
      PDGFR-associated tyrosine kinase inhibitor, SU11248, significantly decreased the
      number of BrdU-positive proliferating endothelial cells and parenchyma cells. In
      conclusion, the present study demonstrates VEGF-dependent continuous angiogenesis
      in the ME of adult mouse brains under normal conditions, which provides new
      insight into our understanding of neurosecretion in the ME.

PMID- 23173694
TI  - The effect of cell cluster size on intracellular nanoparticle-mediated
      hyperthermia: is it possible to treat microscopic tumors?
AB  - AIM: To compare the measured surface temperature of variable size ensembles of
      cells heated by intracellular magnetic fluid hyperthermia with heat diffusion
      model predictions. MATERIALS & METHODS: Starch-coated Bionized NanoFerrite
      (Micromod Partikeltechnologie GmbH, Rostock, Germany) iron oxide magnetic
      nanoparticles were loaded into cultured DU145 prostate cancer cells. Cell pellets
      of variable size were treated with alternating magnetic fields. The surface
      temperature of the pellets was measured in situ and the associated cytotoxicity
      was determined by clonogenic survival assay. RESULTS & CONCLUSION: For a given
      intracellular nanoparticle concentration, a critical minimum number of cells was
      required for cytotoxic hyperthermia. Above this threshold, cytotoxicity increased
      with increasing cell number. The measured surface temperatures were consistent
      with those predicted by a heat diffusion model that ignores intercellular thermal
      barriers. These results suggest a minimum tumor volume threshold of approximately
      1 mm(3), below which nanoparticle-mediated heating is unlikely to be effective as
      the sole cytotoxic agent.

PMID- 23173695
TI  - Community attitudes towards childbearing and abortion among    HIV-positive women
      in Nigeria and Zambia.
AB  - Although stigma towards HIV-positive women for both continuing and terminating a
      pregnancy has been documented, to date few studies have examined relative stigma
      towards one outcome versus the other. This study seeks to describe community
      attitudes towards each of two possible elective outcomes of an HIV-positive
      woman's pregnancy - induced abortion or birth - to determine which garners more
      stigma and document characteristics of community members associated with
      stigmatising attitudes towards each outcome. Data come from community-based
      interviews with reproductive-aged men and women, 2401 in Zambia and 2452 in
      Nigeria. Bivariate and multivariate analyses revealed that respondents from both
      countries overwhelmingly favoured continued childbearing for HIV-positive
      pregnant women, but support for induced abortion was slightly higher in scenarios
      in which anti-retroviral therapy (ART) was unavailable. Zambian respondents held
      more stigmatising attitudes towards abortion for HIV-positive women than did
      Nigerian respondents. Women held more stigmatising attitudes towards abortion for
      HIV-positive women than men, particularly in Zambia. From a sexual and
      reproductive health and rights perspective, efforts to assist HIV-positive women
      in preventing unintended pregnancy and to support them in their pregnancy
      decisions when they do become pregnant should be encouraged in order to combat
      the social stigma documented in this paper.

PMID- 23173696
TI  - Persistent median artery at the forearm.

PMID- 23173697
TI  - Sexual asthenia: Tradamixina versus Tadalafil 5 mg daily.
AB  - BACKGROUND: Reduced libido is widely considered the most prominent symptomatic
      reflection of low testosterone (T) levels in men. Testosterone deficiency (TD)
      afflicts approximately 30% of men aged 40-79 years. This study seeks to evaluate
      the effect of a new natural compound "tradamixina "in order to improve male
      sexual function in elderly men, particularly libido and possible erectile
      dysfunction, versus administration of tadalafil 5 mg daily. METHODS: Seventy
      patients (67.3 +/- 3.7 years) with stable marital relations and affected by
      reduced libido, with or without erectile dysfunction were recruited. They were
      randomly separated in 2 groups A-B of 35. Group A was administered twice a day a
      new compound "Tradamixina" (150 mg of Alga Ecklonia Bicyclis, 396 mg of Tribulus
      Terrestris and 144 mg of D-Glucosamine and N-Acetyl-D-Glucosamine) for two
      months, while Group B was administered tadalafil 5 mg daily, for two months. At
      visit and after 60 days of treatment patients were evaluated by means of detailed
      medical and sexual history, clinical examination, laboratory investigations
      (Total and Free T), instrumental examination (NPTR- nocturnal penile tumescence
      and rigidity test- with Rigiscan). Patients completed a self-administered IIEF
      questionnaire (The international index of erectile function) and SQoLM
      questionnaire (Sexual quality of life Questionnarie-Male). The results pre and
      post treatment were compared by Student t test (p<0.005). RESULTS: After 2 months
      of treatment in group A serum TT levels (230 +/- 18 ng/dl vs 671 +/- 14 ng/dl )
      and FT levels(56 +/- 2.4 pg/ml vs 120 +/- 3.9 pg/ml) increased, while in group B
      serum TT levels (245 +/- 12 ng/dl vs 247 +/- 15 ng/dl ) and FT levels(53 +/- 0.3
      pg/ml vs 55 +/- 0.5 pg/ml) increased not statistically significant. The patient's
      numbers with negative NPTR improved after treatment in group A and B (15 vs 18
      and 13 vs 25 respectively). The IIEF total score in group A increased after
      treatment with tradamixina (15 +/- 1.5 vs 29.77 +/- 1.2); the IIEF total score in
      group B increased slightly (12 +/- 1.3 vs 23.40 +/- 1.2). The SQoLM total score
      improved in both groups (A:16 +/- 2,3 vs 33 +/- 4,1 and B: 16 +/- 3,4 vs 31 +/-
      2,1). CONCLUSION: The treatment twice a day with "Tradamixina" for 2 months
      improved libido in elderly men without side effects of Tadalafil.

PMID- 23173698
TI  - Lead-in treatment with interferon-beta/ribavirin may modify the early hepatitis C
      virus dynamics in pegylated interferon alpha-2b/ribavirin combination for chronic
      hepatitis C patients with the IL28B minor genotype.
AB  - BACKGROUND AND AIM: The most important factor influencing the effect of pegylated
      interferon (PEG-IFN)/ribavirin therapy (PEG) for chronic hepatitis C genotype 1b
      with high viral load is the interleukin 28B (IL28B) genotype. We investigated the
      usefulness of lead-in twice-daily interferon (IFN)-beta/ribavirin therapy (IFN
      beta), and the early hepatitis C virus RNA (HCV-RNA) dynamics was compared
      between PEG and IFN-beta groups according to the IL28B genotype. METHODS: Forty
      six patients were randomly allocated to PEG and IFN-beta groups, and HCV-RNA
      dynamics in an early phase of treatment were analyzed. RESULTS: The patients with
      minor IL28B genotype was 6/23 and 8/23 in IFN-beta and PEG groups, respectively.
      In the patients with IL28B major genotype, viral load reduction was marginally
      greater in IFN-beta group than in PEG group. In contrast, in the patients with
      the IL28B minor genotype, viral load reduction was significantly and numerically
      greater in IFN-beta group than in PEG group at 1 week (2.07 vs. 0.76 log IU/mL, P
      = 0.038), 2 weeks (2.73 vs. 1.01, P = 0.009), 4 weeks (2.72 vs. 1.55, P = 0.059),
      and 12 weeks (4.56 vs. 3.24, P = 0.104). The sustained virological response rates
      in the IL28B major genotype were similar between IFN-beta group (47.1%, 8/17) and
      PEG group (53.3%, 8/15). In contrast, the sustained virological response rates in
      the IL28B minor genotype were numerically higher in IFN-beta group (50.0%, 3/6)
      than in PEG group (12.5%, 1/8), although not statistically significant.
      CONCLUSION: It was suggested that lead-in twice-daily IFN-beta/ribavirin
      treatment followed by PEG-IFN/ribavirin combination therapy may modify the HCV
      RNA dynamics compared with that by PEG-IFN/ribavirin therapy, and it is
      particularly useful for the IL28B minor genotype.

PMID- 23173699
TI  - Cronkhite-Canada syndrome: a case report and review of literature.

PMID- 23173700
TI  - Phylogeny and phylodinamic of Hepatitis C in Italy.
AB  - Hepatitis C virus infection (HCV) is one of the most pressing health emergencies
      in the world with a global prevalence of about 170 million people chronically
      infected worldwide. In Europe, Italy has the highest HCV prevalence (3 - 4.4%)
      with peaks of 12.6 - 26% in Southern regions and the major islands. In Italy HCV
      genotype 1b prevails, and genotype 4 is mainly found in the south of the country
      where the prevalence is particularly high in regions such as
      Calabria.Phylogenetics analysis is a molecular tool widely used to study rapidly
      evolving RNA viruses that establish chronic infections such as HCV. Searching the
      scientific literature, it was found that thirty-nine genetic studies on HCV
      genotypes have been carried out in Italy between 1997 to 2012 years. However,
      phylogenetic analysis was performed only in fourteen out of thirty-nine HCV
      studies (36%) considered. Monitoring the genetic evolution of HCV is an essential
      step to control the local as well as global HCV epidemic and to develop efficient
      preventive and therapeutic strategies.

PMID- 23173701
TI  - West Nile alternative open reading frame (N-NS4B/WARF4) is produced in infected
      West Nile Virus (WNV) cells and induces humoral response in WNV infected
      individuals.
AB  - BACKGROUND: West Nile Virus (WNV) is a flavivirus that requires an efficient
      humoral and cellular host response for the control of neuroinvasive infection. We
      previously reported the existence of six alternative open reading frame proteins
      in WNV genome, one of which entitled WARF4 is exclusively restricted to the
      lineage I of the virus. WARF4 is able to elicit antibodies in WNV infected
      horses; however, there was no direct experimental proof of the existence of this
      novel protein. The purpose of this study was to demonstrate the in vitro
      production of WARF4 protein following WNV infection of cultured VERO cells and
      its immunity in WNV infected individuals. RESULTS: We produced a monoclonal
      antibody against WARF4 protein (MAb 3A12) which detected the novel protein in WNV
      lineage I-infected, cultured VERO cells while it did not react with WNV lineage
      II infected cells. MAb 3A12 specificity to WARF4 protein was confirmed by its
      reactivity to only one peptide among four analyzed that cover the full WARF4
      amino acids sequence. In addition, WARF4 protein was expressed in the late phase
      of WNV lineage I infection. Western blotting and bioinformatics analyses strongly
      suggest that the protein could be translated by programmed -1 ribosomal
      frameshifting process. Since WARF4 is embedded in the NS4B gene, we rename this
      novel protein N-NS4B/WARF4. Furthermore, serological analysis shows that N
      NS4B/WARF4 is able to elicit antibodies in WNV infected individuals. CONCLUSIONS:
      N-NS4B/WARF4 is the second Alternative Reading Frame (ARF) protein that has been
      demonstrated to be produced following WNV infection and might represent a novel
      tool for a better characterization of immune response in WNV infected
      individuals. Further serological as well as functional studies are required to
      characterize the function of the N-NS4B/WARF4 protein. Since the virus might
      actually make an extensive use of ARFs, it appears important to investigate the
      novel six ARF putative proteins of WNV.

PMID- 23173702
TI  - Short communication: HIV type 1 transmitted drug resistance and evidence of
      transmission clusters among recently infected antiretroviral-naive individuals
      from Ugandan fishing communities of Lake Victoria.
AB  - Human immunodeficiency virus type 1 (HIV-1) prevalence and incidence in the
      fishing communities on Lake Victoria in Uganda are high. This population may play
      a role in driving the HIV epidemic in Uganda including the spread of transmitted
      drug resistance (TDR). We report data on TDR in this population among
      antiretroviral (ARV)-naive, recently infected individuals about 5 years after ARV
      scaling-up in Uganda. We identified phylogenetic transmission clusters and
      combined these with volunteer life histories in order to understand the sexual
      networks within this population. From a prospective cohort of 1,000 HIV-negative
      individuals recruited from five communities, 51 seroconverters were identified
      over a period of 2 years. From these, whole blood was collected and population
      sequencing of the HIV-1 pol gene (protease/reverse transcriptase) was performed
      from plasma. Drug resistance mutations (DRMs) were scored using the 2009 WHO list
      for surveillance of TDR. TDR prevalence categories were estimated using the WHO
      recommended truncated sampling technique for the surveillance of TDR for use in
      resource-limited settings (RLS). Of the samples 92% (47/51) were successfully
      genotyped. HIV-1 subtype frequencies were 15/47 (32%) A1, 20/47 (43%) D, 1/47
      (2%) C, 1/47 (2%) G, and 10/47 (21%) unique recombinant forms. Nonnucleoside
      reverse transcriptase inhibitor (NNRTI) drug resistance mutation K103N was
      identified in two individuals and V106A in one (6%) suggesting that the level of
      TDR was moderate in this population. No nucleoside/tide reverse transcriptase
      inhibitor (NRTI) or protease inhibitor (PI) DRMs were detected. In this study, we
      identified five transmission clusters supported by high bootstrap values and low
      genetic distances. Of these, one pair included the two individuals with K103N.
      Two of the genotypic clusters corresponded with reported sexual partnerships as
      detected through prior in-depth interviews. The level of TDR to NNRTIs in these
      ARV-naive individuals was moderate by WHO threshold survey categorization. The
      transmission clusters suggest a high degree of sexual partner mixing between
      members of these communities.

PMID- 23173703
TI  - Development of a gene therapy strategy to target hepatocellular carcinoma based
      inhibition of protein phosphatase 2A using the alpha-fetoprotein promoter
      enhancer and pgk promoter: an in vitro and in vivo study.
AB  - BACKGROUND: Hepatocellular carcinoma (HCC) is one of the leading causes of cancer
      related deaths worldwide. Current therapies are insufficient, making HCC an
      intractable disease. Our previous studies confirmed that inhibition of protein
      phosphatase 2A (PP2A) may provide a promising therapeutic strategy for cancer.
      Unfortunately, constitutive expression of PP2A in normal tissues limits the
      application of PP2A inhibition. Thus, a HCC-specific gene delivery system should
      be developed. The alpha-fetoprotein (AFP) promoter is commonly used in HCC
      specific gene therapy strategies; however, the utility of this approach is
      limited due to the weak activity of the AFP promoter. It has been shown that
      linking the AFP enhancer with the promoter of the non-tissue-specific, human
      housekeeping phosphoglycerate kinase (pgk) gene can generate a strong and HCC
      selective promoter. METHODS: We constructed a HCC-specific gene therapy system to
      target PP2A using the AFP enhancer/pgk promoter, and evaluated the efficiency and
      specificity of this system both in vitro and in vivo. RESULTS: AFP enhancer/pgk
      promoter-driven expression of the dominant negative form of the PP2A catalytic
      subunit alpha (DN-PP2Acalpha) exerted cytotoxic effects against an AFP-positive
      human hepatoma cell lines (HepG2 and Hep3B), but did not affect AFP-negative
      human hepatoma cells (SK-HEP-1) or normal human liver cells (L-02). Moreover, AFP
      enhancer/pgk promoter driven expression of DN-PP2Acalpha inhibited the growth of
      AFP-positive HepG2 tumors in nude mice bearing solid tumor xenografts, but did
      not affect AFP-negative SK-HEP-1 tumors. CONCLUSIONS: The novel approach of AFP
      enhancer/pgk promoter-driven expression of DN-PP2Acalpha may provide a useful
      cancer gene therapy strategy to selectively target HCC.

PMID- 23173704
TI  - The effects of Sutaehwan-Gami on menopausal symptoms induced by ovariectomy in
      rats.
AB  - BACKGROUND: This study was undertaken to evaluate the beneficial effects of a
      modified prescription of Sutaehwan named Sutaehwan-Gami (SG), created by adding
      Rhizoma dioscoreae and Carthami semen to Sutaehwan, on menopausal symptoms.
      METHODS: To evaluate the estrogenic effect of SG, we first examined estrogen
      receptor (ER) activation by SG treatment in breast adenocarcinoma cells and
      confirmed the estrogenic effect of SG in vivo ovariectomized rats. The animals
      were randomized into four groups: Sham operated group (Sham), saline treated
      ovariectomized group (OVX), SG treated group (SG) and raloxifene treated group
      (RLX). Animals were provided with SG at a dose of 500 mg/kg bw/day and RLX at a
      dose of 5.4 mg/kg bw/day with standard rat pellets for 3 months. RESULTS: SG
      significantly increased ERalpha phosphorylation, and its downstream effectors,
      extracellular signal-regulated kinase (ERK) and protein kinase B (Akt)
      phosphorylation in breast adenocarcinoma cells. Treatment with SG reversed
      ovariectomy-induced uterine weight reduction and weight gain. Decreases in the
      levels of GOT and GPT were observed in the SG group. The significantly reduced
      E2beta level in OVX rats was raised by treatment with SG. Moreover, SG
      significantly increased the phosphorylation levels of ERK and Akt in the uterus.
      CONCLUSION: Taken together, these data indicate that SG has phytoestrogen-like
      properties through ERK and Akt activation, implying that it could be protective
      and beneficial for the management of menopausal symptoms.

PMID- 23173705
TI  - Petunia flowers solve the defence/apparency dilemma of pollinator attraction by
      deploying complex floral blends.
AB  - Flowers recruit floral visitors for pollination services by emitting fragrances.
      These scent signals can be intercepted by antagonists such as florivores to
      locate host plants. Hence, as a consequence of interactions with both mutualists
      and antagonists, floral bouquets likely consist of both attractive and defensive
      components. While the attractive functions of floral bouquets have been studied,
      their defensive function has not, and field-based evidence for the deterrence of
      floral-scent constituents is lacking. In field and glasshouse experiments with
      five lines of transgenic Petunia x hybrida plants specifically silenced in their
      ability to release particular components of their floral volatile bouquet, we
      demonstrate that the emission of single floral-scent compounds can dramatically
      decrease damage from generalist florivores. While some compounds are used in host
      location, others prevent florivory. We conclude that the complex blends that
      comprise floral scents are likely sculpted by the selective pressures of both
      pollinators and herbivores.

PMID- 23173706
TI  - EliA facilitates the induction of lipase expression by stearyl alcohol in
      Ralstonia sp. NT80.
AB  - Extracellular lipase activity from Ralstonia sp. NT80 is induced significantly by
      fatty alcohols such as stearyl alcohol. We found that when lipase expression was
      induced by stearyl alcohol, a 14-kDa protein (designated EliA) was produced
      concomitantly and abundantly in the culture supernatant. Cloning and sequence
      analysis revealed that EliA shared 30% identity with the protein-like activator
      protein of Pseudomonas aeruginosa, which facilitates oxidation and assimilation
      of n-hexadecane. Inactivation of the eliA gene caused a significant reduction in
      the level of induction of lipase expression by stearyl alcohol. Furthermore,
      turbidity that was caused by the presence of emulsified stearyl alcohol, an
      insoluble material, remained in the culture supernatant of the DeltaeliA mutant
      during the late stationary phase, whereas the culture supernatant of the wild
      type at 72 h was comparatively clear. In contrast, when lipase expression was
      induced by polyoxyethylene (20) oleyl ether, a soluble material, inactivation of
      eliA did not affect the extracellular lipase activity greatly. These results
      strongly indicate that EliA facilitates the induction of lipase expression,
      presumably by promoting the recognition and/or incorporation of the induction
      signal that is attributed to stearyl alcohol.

PMID- 23173707
TI  - Centenarians and supercentenarians: a black swan. Emerging social, medical and
      surgical problems.
AB  - The Black Swan Theory was described by Nassim Nicholas Taleb in his book "The
      Black Swan". This theory refers to "high-impact, hard-to-predict, and rare events
      beyond the realm of normal expectations". According to Taleb's criteria, a Black
      Swan Event is a surprise, it has a major impact and after the fact, the event is
      rationalized by hindsight, as if it had been expected. For most of human history
      centenarians were a rare and unpredictable phenomenon. The improvements of the
      social-environmental conditions, of medical care, and the quality of life caused
      a general improvement of the health status of the population and a consequent
      reduction of the overall morbidity and mortality, resulting in an overall
      increase of life expectancy. The study of centenarians and supercentenarians had
      the objective to consider this black swan and to evaluate the health, welfare,
      social and economic consequences of this phenomenon.

PMID- 23173708
TI  - Wnt3a induces exosome secretion from primary cultured rat microglia.
AB  - BACKGROUND: Microglia, the immune effector cells of the CNS and the signaling
      molecule Wnt, both play critical roles in neurodevelopment and neurological
      disease. Here we describe the inducible release of exosomes from primary cultured
      rat microglia following treatment with recombinant carrier-free Wnt3a. RESULTS:
      Wnt3a was internalised into microglia, being detectable in early endosomes, and
      secreted in exosomes through a GSK3-independent mechanism. Electron microscopy
      demonstrated that exosomes were elliptical, electron-dense (100 nm) vesicles that
      coalesced with time in vitro. In contrast to microglia, primary cortical neurons
      released exosomes constitutively and the quantity of exosomes released was not
      altered by Wnt3a treatment. The proteomic profile of the microglial-derived
      exosomes was characterised using liquid chromatography-tandem mass spectrometry
      (LC/MS/MS) and the vesicles were found to be associated with proteins involved in
      cellular architecture, metabolism, protein synthesis and protein degradation
      including beta-actin, glyceraldehyde-3-phosphate dehydrogenase, ribosomal
      subunits and ubiquitin (45 proteins in total). Unlike lipopolysaccharide, Wnt3a
      did not induce a neurotoxic, pro-inflammatory phenotype in primary microglia.
      CONCLUSION: These findings reveal a novel mechanism through which Wnt3a signals
      in microglia resulting in the release of exosomes loaded with proteinaceous
      cargo.

PMID- 23173709
TI  - Characterizing the relationship between health utility and renal function after
      kidney transplantation in UK and US: a cross-sectional study.
AB  - BACKGROUND: Chronic allograft nephropathy (CAN) occurs in a large share of
      transplant recipients and it is the leading cause of graft loss despite the
      introduction of new and effective immunosuppressants. The reduction in renal
      function secondary to immunologic and non-immunologic CAN leads to several
      complications, including anemia and calcium-phosphorus metabolism imbalance and
      may be associated to worsening Health-Related Quality of Life. We sought to
      evaluate the relationship between kidney function and Euro-Qol 5 Dimension Index
      (EQ-5Dindex) scores after kidney transplantation and evaluate whether cross
      cultural differences exist between UK and US. METHODS: This study is a secondary
      analysis of existing data gathered from two cross-sectional studies. We enrolled
      233 and 209 subjects aged 18-74 years who received a kidney transplant in US and
      UK respectively. For the present analysis we excluded recipients with multiple or
      multi-organ transplantation, creatinine kinase >=200 U/L, acute renal failure,
      and without creatinine assessments in 3 months pre-enrollment leaving 281
      subjects overall. The questionnaires were administered independently in the two
      centers. Both packets included the EQ-5Dindex and socio-demographic items. We
      augmented the analytical dataset with information abstracted from clinical charts
      and administrative records including selected comorbidities and biochemistry test
      results. We used ordinary least squares and quantile regression adjusted for
      socio-demographic and clinical characteristics to assess the association between
      EQ-5Dindex and severity of chronic kidney disease (CKD). RESULTS: CKD severity
      was negatively associated with EQ-5Dindex in both samples (UK: rho= -0.20,
      p=0.02; US: rho= -0.21, p=0.02). The mean adjusted disutility associated to CKD
      stage 5 compared to CKD stage 1-2 was Delta= -0.38 in the UK sample, Delta= -0.11
      in the US sample and Delta= -0.22 in the whole sample. The adjusted median
      disutility associated to CKD stage 5 compared to CKD stage 1-2 for the whole
      sample was 0.18 (p<0.01, quantile regression). Center effect was not
      statistically significant. CONCLUSIONS: Impaired renal function is associated
      with reduced health-related quality of life independent of possible confounders,
      center-effect and analytic framework.

PMID- 23173710
TI  - Differences in magnetic particle uptake by CNS neuroglial subclasses:
      implications for neural tissue engineering.
AB  - AIM: To analyze magnetic particle uptake and intracellular processing by the four
      main non-neuronal subclasses of the CNS: oligodendrocyte precursor cells;
      oligodendrocytes; astrocytes; and microglia. MATERIALS & METHODS: Magnetic
      particle uptake and processing were studied in rat oligodendrocyte precursor
      cells and oligodendrocytes using fluorescence and transmission electron
      microscopy, and the results collated with previous data from rat microglia and
      astrocyte studies. All cells were derived from primary mixed glial cultures.
      RESULTS: Significant intercellular differences were observed between glial
      subtypes: microglia demonstrate the most rapid/extensive particle uptake,
      followed by astrocytes, with oligodendrocyte precursor cells and oligodendrocytes
      showing significantly lower uptake. Ultrastructural analyses suggest that
      magnetic particles are extensively degraded in microglia, but relatively stable
      in other cells. CONCLUSION: Intercellular differences in particle uptake and
      handling exist between the major neuroglial subtypes. This has important
      implications for the utility of the magnetic particle platform for
      neurobiological applications including genetic modification, transplant cell
      labeling and biomolecule delivery to mixed CNS cell populations.

PMID- 23173712
TI  - Educational strategies in performing cesarean section.
AB  - Cesarean section is a common operation and one of the first surgeries performed
      independently by trainees/residents in obstetrics and gynecology. Determination
      of trainees' technical skills level is dependent upon subjective faculty
      assessment. Based on three studies on learning curves in cesarean section, it is
      recommended that trainees perform between 10-15 and 40 supervised cesarean
      sections before operating independently. Surgical technical skills of
      trainees/residents may be assessed by Objective Structured Assessment of
      Technical Skills (OSATS), which provides a foundation for constructive feedback
      during surgical training. The Danish, Swedish and British Obstetric and
      Gynecological Societies' guidelines on cesarean section were reviewed regarding
      cesarean section surgical technique. Placental removal by traction on the
      umbilical cord is recommended uniformly; however, the Danish guidelines recommend
      one-layer uterine incision closure, whereas the Swedish and British guidelines
      recommend two-layer closure. Maternal complications at cesarean section increase
      when the primary surgeon is a trainee/resident rather than an experienced
      surgeon. Basic surgical proficiencies regarding instruments, sutures and surgical
      technique as well as basic anatomy, should be verified before entering a training
      program for cesarean section. Such a training program for technical and non
      technical skills in cesarean section should include theoretical instruction,
      video tutorials, practical experience and direct supervision. Development of a
      specific OSATS for cesarean section is recommended. Training must be individually
      structured accommodating the differences in trainees' competencies. Before
      clinical training in the operating room begins, all trainees must attain
      standardized cognitive and technical skills.

PMID- 23173711
TI  - Plasmodium serine hydroxymethyltransferase: indispensability and display of
      distinct localization.
AB  - BACKGROUND: Serine hydroxymethyltransferase (SHMT), a pyridoxal phosphate
      dependent enzyme, plays a vital role in the de novo pyrimidine biosynthesis
      pathway in malaria parasites. Two genes have been identified in Plasmodium spp.
      encoding a cytosolic SHMT (cSHMT) and putative mitochondria SHMT (mSHMT), but
      their roles have not been fully investigated. METHODS: The presence of Plasmodium
      SHMT isoforms in the intra-erythrocytic stage was assessed based on their gene
      expression using reverse transcription PCR (RT-PCR). Localization studies of
      Plasmodium SHMT isoforms were performed by transfection of fluorescent-tagged
      gene constructs into P. falciparum and expressions of fluorescent fusion proteins
      in parasites were observed using a laser scanning confocal microscope. Genetic
      targeting through homologous recombination was used to study the essentiality of
      SHMT in Plasmodium spp. RESULTS: Semi-quantitative RT-PCR revealed the expression
      of these two genes throughout intra-erythrocytic development. Localization
      studies using P. falciparum expressing fluorescent-tagged SHMT showed that
      PfcSHMT-red fluorescent fusion protein (PfcSHMT-DsRed) is localized in the
      cytoplasm, while PfmSHMT-green fluorescent fusion protein (PfmSHMT-GFP) co
      localized with MitotrackerTM-labelled mitochondria as predicted. The essentiality
      of plasmodial cSHMT was inferred from transfection experiments where recovery of
      viable knock-out parasites was not achieved, unless complemented with a
      functional equivalent copy of shmt. CONCLUSIONS: Distinct compartment
      localizations of PfSHMT were observed between cytoplasmic and mitochondrial
      isoforms, and evidence was provided for the indispensable role of plasmodial
      cSHMT indicating it as a valid target for development of novel anti-malarials.

PMID- 23173713
TI  - The isotropic fractionator provides evidence for differential loss of hippocampal
      neurons in two mouse models of Alzheimer's disease.
AB  - BACKGROUND: The accumulation of amyloid beta (Abeta) oligomers or fibrils is
      thought to be one of the main causes of synaptic and neuron loss, believed to
      underlie cognitive dysfunction in Alzheimer's disease (AD). Neuron loss has
      rarely been documented in amyloid precursor protein (APP) transgenic mouse
      models. We investigated whether two APP mouse models characterized by different
      folding states of amyloid showed different neuronal densities using an accurate
      method of cell counting. FINDINGS: We examined total cell and neuronal
      populations in Swedish/Indiana APP mutant mice (TgCRND8) with severe Abeta
      pathology that includes fibrils, plaques, and oligomers, and Dutch APP mutant
      mice with only Abeta oligomer pathology. Using the isotropic fractionator, we
      found no differences from control mice in regional total cell populations in
      either TgCRND8 or Dutch mice. However, there were 31.8% fewer hippocampal neurons
      in TgCRND8 compared to controls, while no such changes were observed in Dutch
      mice. CONCLUSIONS: We show that the isotropic fractionator is a convenient method
      for estimating neuronal content in milligram quantities of brain tissue and
      represents a useful tool to assess cell loss efficiently in transgenic models
      with different types of neuropathology. Our data support the hypothesis that
      TgCRND8 mice with a spectrum of Abeta plaque, fibril, and oligomer pathology
      exhibit neuronal loss whereas Dutch mice with only oligomers, showed no evidence
      for neuronal loss. This suggests that the combination of plaques, fibrils, and
      oligomers causes more damage to mouse hippocampal neurons than Abeta oligomers
      alone.

PMID- 23173714
TI  - C1-INH concentrate for treatment of acute hereditary angioedema: a pediatric
      cohort from the I.M.P.A.C.T. studies.
AB  - BACKGROUND: We analyzed the clinical response of pediatric and adolescent
      hereditary angioedema (HAE) patients to pdC1-INH in the International Multicenter
      Prospective Angioedema C1-INH Trials (I.M.P.A.C.T.) 1 and 2. METHODS: Patients
      included in this post hoc analysis of prospectively collected data were between
      10 and 18 yr old with type I or II HAE and a documented history of abdominal or
      facial attacks. Patients received a single injection of pdC1-INH concentrate
      (Berinert((r)) , CSL Behring, Marburg, Germany) 20 U/kg. Efficacy end-points were
      time from the administration of study drug to onset of symptom relief and time to
      complete relief of all symptoms. RESULTS: Seven pediatric patients were included
      in I.M.P.A.C.T.1 with only 1 attack analyzed per patient. Median time to onset of
      relief was 0.42 h and to complete resolution was 8.08 h. No patient experienced a
      worsening of symptoms during the 0-4-h assessment period. Nine patients who
      experienced a total of 115 attacks were included in the analysis of
      I.M.P.A.C.T.2. Abdominal attacks were rated as 'severe' more frequently than were
      other types of attacks. The number of attacks per patient ranged from 2 to 42,
      and study participation ranged from 1 to 38 months. Median times to onset of
      symptom relief and to complete symptom resolution were 0.49 h and 14.1 h,
      respectively. Of 4 treatment-emergent adverse events in both studies, only 2 were
      considered related to treatment. CONCLUSIONS: Study results showed that outcomes
      with pdC1-INH treatment of HAE in pediatric patients are comparable with outcomes
      in adults.

PMID- 23173715
TI  - Identifying stage-specific protein subnetworks for colorectal cancer.
AB  - BACKGROUND: In recent years, many algorithms have been developed for network
      based analysis of differential gene expression in complex diseases. These
      algorithms use protein-protein interaction (PPI) networks as an integrative
      framework and identify subnetworks that are coordinately dysregulated in the
      phenotype of interest. MOTIVATION: While such dysregulated subnetworks have
      demonstrated significant improvement over individual gene markers for classifying
      phenotype, the current state-of-the-art in dysregulated subnetwork discovery is
      almost exclusively limited to binary phenotype classes. However, many clinical
      applications require identification of molecular markers for multiple classes.
      APPROACH: We consider the problem of discovering groups of genes whose expression
      signatures can discriminate multiple phenotype classes. We consider two alternate
      formulations of this problem (i) an all-vs-all approach that aims to discover
      subnetworks distinguishing all classes, (ii) a one-vs-all approach that aims to
      discover subnetworks distinguishing each class from the rest of the classes. For
      the one-vs-all formulation, we develop a set-cover based algorithm, which aims to
      identify groups of genes such that at least one gene in the group exhibits
      differential expression in the target class. RESULTS: We test the proposed
      algorithms in the context of predicting stages of colorectal cancer. Our results
      show that the set-cover based algorithm identifying "stage-specific" subnetworks
      outperforms the all-vs-all approaches in classification. We also investigate the
      merits of utilizing PPI networks in the search for multiple markers, and show
      that, with correct parameter settings, network-guided search improves
      performance. Furthermore, we show that assessing statistical significance when
      selecting features greatly improves classification performance.

PMID- 23173716
TI  - Sex workers talk about sex work: six contradictory characteristics of legalised
      sex work in Melbourne, Australia.
AB  - Despite research suggesting that legal sex work is safe and that emotional risks
      and social stigma are of greater concern than health risks, much research on sex
      work has focused on health risks. Given the legalisation of sex work in Victoria,
      Australia, it is timely to look beyond health. Three focus groups were conducted
      with a total of 14 female sex workers on their experience of legal sex work, both
      positive and negative, and the social acceptability of their profession. Thematic
      analysis was used to identify the key ways that sex workers described sex work.
      Women saw legal sex work as safer than illegal sex work, but still not socially
      acceptable. However, they also described six contradictory elements of sex work,
      which was seen as: financially rewarding and entrapping; empowering and
      demeaning; increasing some opportunities while reducing others; flexible and
      demanding; offering both intimacy and competition; and leading to a 'double
      life'. While legalisation has improved the safety of sex work, stigma and
      discrimination persist.

PMID- 23173717
TI  - Are mammographic changes in the tumor bed more pronounced after intraoperative
      radiotherapy for breast cancer? Subgroup analysis from a randomized trial (TARGIT
      A).
AB  - Intraoperative radiotherapy (IORT) with low-energy x-rays is increasingly used in
      breast-conserving therapy (BCT). Previous non-randomized studies have observed
      mammographic changes in the tumor bed to be more pronounced after IORT. The
      purpose of this study was to reassess the postoperative changes in a randomized
      single-center subgroup of patients from a multicenter trial (TARGIT-A). In this
      subgroup (n = 48) 27 patients received BCT with IORT, 21 patients had BCT with
      standard whole-breast radiotherapy serving as controls. Overall 258 postoperative
      mammograms (median follow-up 4.3 years, range 3-8) were retrospectively evaluated
      by two radiologists in consensus focusing on changes in the tumor bed. Fat
      necroses showed to be significantly more frequent (56% versus 24%) and larger
      (8.7 versus 1.6 sq cm, median) after IORT than those in controls. Scar
      calcifications were also significantly more frequent after IORT (63% versus 19%).
      The high incidence of large fat necroses in our study confirms previous study
      findings. However, the overall higher incidence of calcifications in the tumor
      bed after IORT represents a new finding, requiring further attention.

PMID- 23173718
TI  - Effects of 5-alpha reductase inhibitors on erectile function, sexual desire and
      ejaculation.
AB  - INTRODUCTION: Treatment with 5-alpha reductase inhibitors (5ARI) is commonly
      utilized for the treatment of benign prostatic hyperplasia (BPH). The true
      prevalence of sexual side effects with 5ARI treatment is currently unknown. AREAS
      COVERED: The current article reviews the reported adverse effects of 5ARI in
      regard to erectile function, sexual desire and ejaculation. A PubMed search was
      performed of all articles from 1990 to present, which reported any sexual side
      effects with finasteride or dutasteride. Preference was given to more recent and
      human studies where available. EXPERT OPINION: Clinical trials with 5ARI report
      prevalence rates of de novo erectile dysfunction of 5 - 9%. Decreased circulating
      dihydrotestosterone (DHT) resulting from 5ARI use is associated with diminished
      sexual desire and/or orgasm. The presence of adverse sexual effects is associated
      with decreased self-esteem, quality of life and ability to maintain an intimate
      relationship. Inhibition of 5ARI additionally influences progesterone and
      deoxycorticosterone levels and may alter psychological functions, including
      increased depression, melancholy and loss of general well being. Ejaculatory
      dysfunction has not been well studied in patients using 5ARI. Patients receiving
      therapy with 5ARI should be counseled as to potential sexual and psychological
      adverse effects. Future clinical studies are needed to further investigate the
      sexual side effects associated with this class of drugs.

PMID- 23173719
TI  - Hemodynamic responses in amygdala and hippocampus distinguish between aversive
      and neutral cues during Pavlovian fear conditioning in behaving rats.
AB  - Lesion and electrophysiological studies in rodents have identified the amygdala
      and hippocampus (HPC) as key structures for Pavlovian fear conditioning, but
      human functional neuroimaging studies have not consistently found activation of
      these structures. This could be because hemodynamic responses cannot detect the
      sparse neuronal activity proposed to underlie conditioned fear. Alternatively,
      differences in experimental design or fear levels could account for the
      discrepant findings between rodents and humans. To help distinguish between these
      alternatives, we used tissue oxygen amperometry to record hemodynamic responses
      from the basolateral amygdala (BLA), dorsal HPC (dHPC) and ventral HPC (vHPC) in
      freely-moving rats during the acquisition and extinction of conditioned fear. To
      enable specific comparison with human studies we used a discriminative paradigm,
      with one auditory cue [conditioned stimulus (CS)+] that was always followed by
      footshock, and another auditory cue (CS-) that was never followed by footshock.
      BLA tissue oxygen signals were significantly higher during CS+ than CS- trials
      during training and early extinction. In contrast, they were lower during CS+
      than CS- trials by the end of extinction. dHPC and vHPC tissue oxygen signals
      were significantly lower during CS+ than CS- trials throughout extinction. Thus,
      hemodynamic signals in the amygdala and HPC can detect the different patterns of
      neuronal activity evoked by threatening vs. neutral stimuli during fear
      conditioning. Discrepant neuroimaging findings may be due to differences in
      experimental design and/or fear levels evoked in participants. Our methodology
      offers a way to improve translation between rodent models and human neuroimaging.

PMID- 23173720
TI  - QuantiFERON-TB Gold In-Tube test for diagnosis of latent tuberculosis (TB)
      infection in solid organ transplant candidates: a single-center study in an area
      endemic for TB.
AB  - BACKGROUND: The prevalence of Mycobacterium tuberculosis in transplant recipients
      is estimated to be 50 times higher than in the general population, with a
      mortality rate of around 40%. Diagnosis and treatment of latent tuberculosis (TB)
      infection (LTBI) is an essential strategy for TB control. In this study we
      compared the QuantiFERON-TB Gold In-Tube test (QFT) with the tuberculin skin test
      (TST) for detection of LTBI in solid organ transplant (SOT) candidates. PATIENTS
      AND METHODS: Between March 2008 and September 2011, 187 transplant candidates,
      who were referred to the transplant clinic of Imam-Khomeini Hospital, were
      enrolled in the study. Patients were screened for LTBI with both QFT and TST.
      Twenty-three patients (12.3%) were excluded for failure to follow up. Concordance
      between the 2 tests, and variables associated with test discordance were
      assessed. RESULTS: The mean age of patients was 40 years (range: 11-65) and male
      to-female ratio was 1.2 (88/76). TST and QFT were positive in 26 (15.9%) and 33
      (20.1%) patients, respectively. Five cases (3.1%) had indeterminate QFT. Overall
      agreement between QFT and TST was about 80% (k = 0.32, P-value = 0.0001).
      CONCLUSION: Considering the fair overall agreement between the 2 tests, and
      greater ease of the QFT from the patient's point of view, QFT is recommended for
      detection of LTBI in SOT candidates.

PMID- 23173721
TI  - Usefulness of a fast track list for anxious patients in a upper GI endoscopy.
AB  - BACKGROUND: To determine whether patients with no alarm signs who ask the
      endoscopist to shorten their waiting time due to test result anxiety, represent a
      risk category for a major organic pathology. METHODS: At our open-access
      endoscopy service, we set up an expedite list for six months for outpatients who
      complained that the waiting time for gastroscopy was too long. Over this period
      we studied 373 gastroscopy patients. In addition to personal details, we
      collected information on the presence of Hp infection and compliance with
      dyspepsia guideline indications for gastroscopy. RESULTS: Average waiting time
      was 38.2 days (SD 12.7). The 66 patients who considered the waiting time too long
      underwent gastroscopy within 15 days. We made 5 diagnoses of esophageal and
      gastric tumour and gastric ulcer (7.6%) among the expedite list patients and 14
      (4.6%) among those on the normal list (p=0.31). On including duodenal peptic
      disease in the analysis, the total prevalence rate rose to 19.7% in the short
      wait group and to 10.4% (p=0.036) in the longer-wait group. DISCUSSION AND
      CONCLUSIONS: Our data suggests that asking to be fast-tracked does not have
      prognostic impact on the diagnosis of a major (gastric ulcer and cancer)
      pathology.

PMID- 23173722
TI  - Amperometric nitric oxide sensor based on nanoporous platinum phthalocyanine
      modified electrodes.
AB  - This article describes the fabrication of electropolymerized Metallo 4', 4",
      4''', 4'''' tetra-amine phthalocyanine (poly-MTAPc) modified electrodes for the
      detection of nitric oxide (NO) in phosphate-buffered saline (PBS) at pH 7.4. A
      two-step synthetic protocol using a laboratory microwave reactor was adopted to
      provide three MTAPc complexes bearing different metal centers (M = Cu(2+):
      CuTAPc, M = Zn(2+): ZnTAPc, and M = Pt(2+): PtTAPc). The MTAPc complexes and the
      intermediates were characterized by MALDI-TOF mass spectrometry, UV-vis
      spectroscopy, (1)H NMR spectroscopy, and elemental analysis. The MTAPc products
      were separately electropolymerized either onto a glassy carbon (GC) electrode as
      a thin-film or within the pores of Anodisc nanoporous alumina membrane as a
      densely packed array of poly-MTAPc nanotubes to produce two electrode systems. In
      the latter system, the surface area enhancement provided by the nanotube-arrayed
      morphology of the poly-MTAPc enabled a high faradaic (signal) to capacitative
      (background) current during NO electro-oxidation. Amperometric detection of NO
      using these two electrode systems shows that the sensitivity and linear ranges
      were insensitive to the metal centers (M = Cu(2+), Zn(2+), and Pt(2+)) of the
      poly-MTAPc material.

PMID- 23173723
TI  - Effect of tooth isolation on laser Doppler readings.
AB  - AIM: To measure differences between single (STI) and multiple teeth isolation
      (MTI), pulpal blood flow (PBF) was assessed using laser Doppler flowmetry (LDF).
      METHODOLOGY: Pulpal blood flow of twenty maxillary incisors with no restorations
      or abnormal responses to sensitivity tests in healthy patients between 24 and 42
      years of age was measured in perfusion units (PU). STI (isolation of only the
      tooth undergoing blood flow assessment) and MTI (isolation including the
      maxillary right to the maxillary left canine) recordings were taken with regular
      blood flow (RBF) and with local infiltration (LI) with vasoconstrictor. anova and
      Tukey HSD tests were used for statistical analysis. RESULTS: The mean PBF with
      regular blood flow conditions was significantly different between single tooth
      isolation [5.53 PU (SD +/- 2.98)] and multiple tooth isolation [2.85 PU (SD +/-
      2.13)] (P < 0.01). When local anaesthesia was administered (LI), the PBF was
      significantly different between single tooth isolation [2.95 PU (SD +/- 2.48)]
      and multiple tooth isolation [1.32 PU (SD +/- 0.70)] (P < 0.05). Significant
      differences in PBF also existed between single tooth isolation under regular
      blood flow conditions and with local anaesthesia (P < 0.01), between single tooth
      isolation under regular blood flow conditions and multiple tooth isolation with
      local anaesthesia (P < 0.01), and between multiple tooth isolation under regular
      blood flow conditions and with local anaesthesia (P < 0.05). CONCLUSIONS: Pulpal
      blood flow measurements could be obtained with multiple teeth isolation and
      single tooth isolation. Multiple teeth isolation blocked signal contamination
      better. Single tooth isolation provided significantly different readings for
      regular blood flow and LI conditions and may therefore provide an option for
      pulpal blood flow assessment with LDF.

PMID- 23173724
TI  - Analysis of altered microRNA expression profiles in peripheral blood mononuclear
      cells from patients with primary biliary cirrhosis.
AB  - BACKGROUND AND AIM: MicroRNA, as an important regulator of gene expression, has
      been found to be associated with several diseases. MicroRNA expression profiles
      have been identified in several autoimmune diseases, such as rheumatoid
      arthritis, systemic lupus erythematosus, and multiple sclerosis. However, the
      expression profile in peripheral blood mononuclear cells (PBMCs) from primary
      biliary cirrhosis (PBC) patients and the role of microRNA in PBC remained
      unclear. The present study aimed to explore abnormal microRNA regulation in PBC.
      METHODS: MicroRNA array was performed in PBMCs obtained from PBC patients versus
      healthy controls. Then, six of the 17 differentially expressed microRNAs were
      confirmed using quantitative real-time polymerase chain reaction. Based on
      bioinformatics analysis, we identified the potential biological processes and
      significant signaling pathways affected by these microRNAs, and generated the
      microRNA-gene network. RESULTS: According to microRNA array, a total of 17
      microRNAs were found to be differentially expressed. Six microRNAs have been
      validated using quantitative real-time polymerase chain reaction, and the results
      were consistent with microRNA array analysis. The bioinformatics analysis showed
      that the potential target genes of these microRNAs were involved in cell
      proliferation, cell differentiation, apoptosis, and signal transduction.
      Similarly, these microRNAs also affected endocytosis, mitogen-activated protein
      kinase signaling pathway, transforming growth factor-beta signaling pathway, Wnt
      signaling pathway, calcium signaling pathway, etc. CONCLUSION: In the present
      study, 17 microRNAs were identified to be differentially expressed in PBMCs from
      PBC patients. Functional bioinformatics analysis demonstrated that prediction
      genes targeted by these microRNAs were involved in multiple biological processes
      and signaling pathways. The present study offers intriguing new perspectives on
      the involvement of microRNA in PBC, but the precise mechanisms need to be
      validated further.

PMID- 23173725
TI  - Model systems for rapid and slow induction of apoptosis obtained by inducible
      expression of pro-apoptotic proteins.
AB  - Killing tumor cells is a central goal of non-surgical cancer therapy and
      induction of apoptosis in the malignant cells is the major strategy used to
      achieve it. However, this may have serious drawbacks, since apoptotic cells
      reportedly induce immunological tumor tolerance and activate a tumor repopulation
      program. The debate on which type of cell death has the most beneficial
      therapeutic effects in cancer treatment is intense and controversial. Stringently
      regulated, doxycycline-inducible transgene expression systems trigger cell death
      in a defined manner, which might help us find answers to these problems. A
      conditional suicide switch established transiently in Jurkat T-cells was used to
      test a set of pro-apoptotic proteins for their potency to induce cell death. The
      activated forms of caspase-3 (revCasp-3) and Bid (tBid) were very effective and,
      therefore, analyzed after stable integration into human leukemia and murine
      melanoma cell lines. Expression of either protein resulted in more than 95% cell
      death, but with strongly different kinetics. 85% cell death was observed if tBid
      and revCasp-3 were expressed for 4-6 hours and 18-24 hours, respectively. The
      human cell lines expressing these suicide switches can serve as cancer models in
      xeno-transplanted mice, the corresponding murine cell lines allow syngeneic and
      allogeneic murine cancer models to be established. 

PMID- 23173726
TI  - Molecular epidemiology of measles virus in Italy, 2002-2007.
AB  - BACKGROUND: The European Regional Office of the World Health Organization
      (WHO/Europe) developed a strategic approach to halt the indigenous transmission
      of measles in its 53 Member States by 2015. In view of the goal of measles
      elimination, it is of great importance to assess the circulation of wild-type
      measles virus (MV). Genetic analysis is indispensable to understand the
      epidemiology of measles. METHODS: Urine and saliva samples were collected between
      May 2002 and December 2007, in order to find the origins and routes of wild type
      measles virus circulation. RT-PCR was performed on a total of 414 clinical
      samples of patients from different Italian regions. The results confirmed the
      genome presence in 199 samples, out of which 179 were sequenced. The sequences
      were genotyped by comparing the fragment coding for the carboxyl terminus of the
      nucleoprotein (450 nucleotides) with that one of the WHO reference strains.
      RESULTS: From the year 2002 to the year 2007 phylogenetic analysis of measles
      sequences showed a predominant circulation of the D7 genotype in the Italian
      territory for the years 2002-2004. This genotype was replaced by D4 and B3
      genotypes in the biennium 2006-2007. During the same period C2, A, D5 and D8
      genotypes were also detected. CONCLUSIONS: Genetic characterization of wild-type
      MV provides a means to study the transmission pathways of the virus, and is an
      essential component of laboratory-based surveillance. Knowledge of currently
      circulating measles virus genotype in Italy will help in monitoring the success
      of the measles elimination programme and will contribute to evaluate the
      effectiveness of future vaccination campaigns.

PMID- 23173727
TI  - Testosterone deficiency causes penile fibrosis and organic erectile dysfunction
      in aging men. Evaluating association among Age, TDS and ED.
AB  - INTRODUCTION: We studied the possible correlation between age, testosterone
      deficiency, cavernosal fibrosis and erectile dysfunction (ED). METHODS: 47
      patients with ED were enrolled between September 2010 and October 2011. IIEF-EF
      score, NPTR test using the Rigiscan method, total and free testosterone levels,
      and cavernosum biopsy were carried out on all patients. Patients aged 65 or over
      were defined as Old Age (OA) while patients under 65 were defined Young age (YA).
      The strength of the relationships found was estimated by Odds Ratio. RESULTS: 74%
      of patients with values of over 52% collagen fibers in the corpora cavernosa were
      found to have organic ED. A significant difference was found in age, percentage
      of collagen fibers, testosterone levels between patients with Positive Rigiscan
      (PR) and Negative Rigiscan (NR). Hypotestosteronaemia increased the risk of ED
      with PR (OR: 21.4, 95% CI: 20.2-22.6) and in both young age patients (OR: 4.3,
      95% CI: 2.4-6.2) and old age patients (OR: 15.5, 95% CI: 13.4-17.6). Moreover
      cavernosal fibrosis increased the risk of ED with PR in both young age patients
      (OR: 8.2, 95% CI: 6.4-10.0 and old age patients (OR: 24.6, 95% CI: 20.8-28.4).
      CONCLUSIONS: This study demonstrates a strong association among age, testosterone
      deficiency, cavernosal fibrosis and ED with PR. Age, testosterone deficiency and
      cavernosal fibrosis are potentially correctable factors of cavernosal fibrosis
      and organic ED. Further, prospective studies are needed to evaluate if
      testosterone treatment, alone or in association with PDE5 inhibitors, may lower
      the risk of cavernosal fibrosis or decrease the severity the fibrosis in ED
      patients.

PMID- 23173728
TI  - Performance of a point-of-care device in determining prothrombin time in supra
      therapeutic INRs.
AB  - INTRODUCTION: Point-of-care (POC) devices have been widely adopted for monitoring
      prothrombin time (PT) (INR) following the demonstration of their accuracy
      compared to standard INR determination. However, guidelines suggest confirmation
      of POC results when INRs increase above therapeutic range, due to concerns
      regarding possible inferior performance of POC devices in high INR levels.
      Unfortunately, patients with supra-therapeutic INRs are underrepresented in
      studies that validated these devices. METHODS: We performed a prospective
      evaluation of the performance of a POC device in monitoring oral anticoagulation
      in patients with INR values above 3.5 in a University outpatient anticoagulation
      clinic. During a 6-month period, 2322 INR determinations were performed with a
      POC device, and results above 3.5 were immediately repeated on an automated
      coagulometer. RESULTS: Dual INR determinations by two methods were obtained in
      160 visits, with a mean INR from the POC device of 4.52 +/- 0.96. Both classical
      statistics and clinical concordance analysis yielded satisfactory results when
      the two methods were compared. CONCLUSION: Our results demonstrate that POC
      devices present good correlation with standard laboratory methods for PT
      determination in supra-therapeutic INRs and that differences in clinical
      management do not support the need for systematic confirmation of these results
      in nonbleeding patients.

PMID- 23173729
TI  - A metabolic signature for long life in the Caenorhabditis elegans Mit mutants.
AB  - Mit mutations that disrupt function of the mitochondrial electron transport chain
      can, inexplicably, prolong Caenorhabditis elegans lifespan. In this study we use
      a metabolomics approach to identify an ensemble of mitochondrial-derived alpha
      ketoacids and alpha-hydroxyacids that are produced by long-lived Mit mutants but
      not by other long-lived mutants or by short-lived mitochondrial mutants. We show
      that accumulation of these compounds is dependent on concerted inhibition of
      three alpha-ketoacid dehydrogenases that share dihydrolipoamide dehydrogenase
      (DLD) as a common subunit, a protein previously linked in humans with increased
      risk of Alzheimer's disease. When the expression of DLD in wild-type animals was
      reduced using RNA interference we observed an unprecedented effect on lifespan -
      as RNAi dosage was increased lifespan was significantly shortened, but, at higher
      doses, it was significantly lengthened, suggesting that DLD plays a unique role
      in modulating length of life. Our findings provide novel insight into the origin
      of the Mit phenotype.

PMID- 23173730
TI  - Competitive amplification of differentially melting amplicons (CADMA) improves
      KRAS hotspot mutation testing in colorectal cancer.
AB  - BACKGROUND: Cancer is an extremely heterogeneous group of diseases traditionally
      categorized according to tissue of origin. However, even among patients with the
      same cancer subtype the cellular alterations at the molecular level are often
      very different. Several new therapies targeting specific molecular changes found
      in individual patients have initiated the era of personalized therapy and
      significantly improved patient care. In metastatic colorectal cancer (mCRC) a
      selected group of patients with wild-type KRAS respond to antibodies against the
      epidermal growth factor receptor (EGFR). Testing for KRAS mutations is now
      required prior to anti-EGFR treatment, however, less sensitive methods based on
      conventional PCR regularly fail to detect KRAS mutations in clinical samples.
      METHODS: We have developed sensitive and specific assays for detection of the
      seven most common KRAS mutations based on a novel methodology named Competitive
      Amplification of Differentially Melting Amplicons (CADMA). The clinical
      applicability of these assays was assessed by analyzing 100 colorectal cancer
      samples, for which KRAS mutation status has been evaluated by the commercially
      available TheraScreen(r) KRAS mutation kit. RESULTS: The CADMA assays were
      sensitive to at least 0.5% mutant alleles in a wild-type background when using 50
      nanograms of DNA in the reactions. Consensus between CADMA and the TheraScreen
      kit was observed in 96% of the colorectal cancer samples. In cases where
      disagreement was observed the CADMA result could be confirmed by a previously
      published assay based on TaqMan probes and by fast COLD-PCR followed by Sanger
      sequencing. CONCLUSIONS: The high analytical sensitivity and specificity of CADMA
      may increase diagnostic sensitivity and specificity of KRAS mutation testing in
      mCRC patients.

PMID- 23173731
TI  - Natural history and clinical response: "it's the virus, stupid, or is it the
      host?".
AB  - A major goal of modern medicine is the application of personalized therapies,
      consisting of decisions and practices tailored to the individual patient.
      Information about genetic variants, either mutant or polymorphic, represents the
      basis for the development of this clinical approach. Recently, several
      independent genome-wide association studies (GWAS) have identified two single
      nucleotide polymorphisms (SNPs) on the IL28B locus associated with HCV
      containment, spontaneous clearance, treatment response, and disease progression.
      In this minireview we will concisely discuss some critical genetic concepts that
      may have possible implications for clinical decisions in the treatment of HCV
      infection.

PMID- 23173733
TI  - Precisely controlled smart polymer scaffold for nanoscale manipulation of
      biomolecules.
AB  - We demonstrate the application of a novel smart surface to modulate the
      orientation of immobilized double stranded DNA (dsDNA) and the conformation of a
      polymer scaffold through variation in buffer pH and ionic strength. An amphoteric
      poly(dimethylacrylamide) based coating containing weak acrylamido acids and
      bases, which are copolymerized together with the neutral monomer, is covalently
      bound to the surface. The coating can be made to contain any desired amount of
      buffering and titrant ionogenic monomers, allowing control of the surface charge
      when the surface is bathed in a given buffer pH. Spectral self-interference
      fluorescence microscopy (SSFM) is utilized to precisely quantify both the DNA
      orientation and the polymer conformation with subnanometer resolution. It is
      possible to utilize the polymer scaffold to functionalize a variety of common
      materials used in microfabrication, making it a general purpose building block
      for the next generation of nanomachines and biosensors.

PMID- 23173732
TI  - Assessment of cervical lymph node metastasis for therapeutic decision-making in
      squamous cell carcinoma of buccal mucosa: a prospective clinical analysis.
AB  - BACKGROUND: Cervical metastasis has a tremendous impact on the prognosis in
      patients with carcinomas of the head and neck and the frequency of such spread is
      greater than 20% for most squamous cell carcinomas. With emerging evidence, focus
      is shifting to conservative neck procedures aimed at achieving good shoulder
      function without compromising oncologic safety. The purpose of this study was to
      analyze the pattern of nodal metastasis in patients presenting with squamous cell
      carcinoma of buccal mucosa. MATERIALS AND METHODS: This was a prospective
      clinical analysis of patients who were histologically diagnosed with squamous
      cell carcinoma of the buccal cavity and clinically N1 and had not received
      treatment anywhere else. Patients were analyzed for age and sex distribution,
      tumor staging, location, and metastasis. RESULTS: The incidence of metastatic
      lymph node in T4 (n=44) was the highest, that is, level I was 100% (44/44), level
      II was 43.18% (19/44), level III was 15.90% (7/44), and level IV was 4.5% (2/44).
      Level V was free of metastasis. Among T3 (n=10) lesions, incidence of metastasis
      in level I was 100% (10/10), level II was 20% (2/10), and level III, IV, and V
      were free of metastasis. Among T2 (n=6) lesions, incidence of lymph node
      metastasis in level I was 100% (6/6) and all other levels of lymph nodes were
      found free of metastasis. CONCLUSION: Lymphatic spread from carcinoma of the
      buccal mucosa is low. Involvement of level IV is seen in only 3% of patients. A
      more conservative approach to the neck in patients with carcinoma of the buccal
      mucosa is recommended.

PMID- 23173734
TI  - Intranasal administration of antiretroviral-loaded micelles for anatomical
      targeting to the brain in HIV.
AB  - AIM: To investigate the intranasal administration of poly(ethylene oxide)
      poly(propylene oxide) polymeric micelles loaded with high payloads of the first
      line antiretroviral drug efavirenz for targeting to the CNS. METHODS & MATERIALS:
      The effect of micellar size and composition and drug payload was assessed,
      employing simple micelles made of a highly hydrophilic copolymer, poloxamer F127,
      loaded with 20 mg/ml drug and mixed micelles containing 75% of a poloxamine of
      intermediate hydrophobicity, T904, and 25% F127 loaded with 20 and 30 mg/ml drug.
      F127 confers high physical stability, while T904 substantially improves the
      encapsulation capacity of the micelles. RESULTS: The bioavailability of the drug
      in the CNS was increased fourfold and the relative exposure index (ratio between
      the area under the curve in the CNS and plasma) was increased fivefold with
      respect to the same system administered intravenously. CONCLUSION: These findings
      demonstrate the potential of this scalable and cost-viable strategy to address
      the HIV sanctuary in the CNS.

PMID- 23173735
TI  - Tunical plication in the management of penile curvature due La Peyronie's
      disease. Our experience on 47 cases.
AB  - BACKGROUND: Peyronie's disease is an acquired connective tissue disorder of the
      penile tunica albuginea with fibrosis and inflammation. The disease produces
      palpable plaques, penile curvature and pain during erections. Patients report
      negative effects in four major domains: physical appearance and self-image,
      sexual function and performance. These changes damage sexual life and compromise
      the quality of life. Our objective is to review the patient's sexual life after
      penile tunical plicature using the International Index of Erectile Function
      (IIEF) and the Sexual Encounter Profile (SEP) questionnaires. METHODS: A total of
      47 patients with Peyronie's disease (PD) were enrolled at our urology department
      and they underwent correction of penile deviation between February 2009 and March
      2010. Mean patient age was 56 years and mean follow-up was 24 months. Patients
      with painless PD plaque with no progression in angulation for at least 12 months
      were chosen for surgery. They underwent a penile tunical plication.IIEF and SEP
      questionnaire were administered to all patients. RESULTS: Of all treated
      patients, 94% were able to insert their penis in the partner's vagina (p<0.01;
      SEP question 2), compared with 62% preoperatively and 90% of them was satisfied
      overall with the sexual intercourse (p<0.01; SEP question 5) .Patients had a
      significantly higher endpoint and a greater change from baseline for the
      remaining SEP questions related to achievement of an erection, satisfaction of
      erection hardness (SEP questions 1 and 4; p < 0:001).We reported a significant
      improvement in the IIEF scores (from a baseline total score of 25.2 +/- 3.2 to a
      final score of 38.3 +/- 5.2; P<0.01). It resulted in significantly higher
      endpoint IIEF scores across all five IIEF domains: Erectile Function, Intercourse
      Satisfaction, Orgasmic Function, Sexual Desire and Overall Satisfaction. The main
      complaint was penile shortening (28 patients, 60%), feeling of the suture during
      flaccidity and tumescence (37 patients, 80%). CONCLUSION: Patient quality of life
      improved after surgery thanks to the improvement of their sexual life. The
      complications are unimportant and few bother symptoms are reported. The
      significant improvement in erectile function was also supported by IIEF and SEP
      questionnaire data. Nowadays tunical plication is a safe, advantageous and useful
      technique to treat patients suffering of Peyronie's disease.

PMID- 23173736
TI  - Auxin as a player in the biocontrol of Fusarium head blight disease of barley and
      its potential as a disease control agent.
AB  - BACKGROUND: Mechanisms involved in the biological control of plant diseases are
      varied and complex. Hormones, including the auxin indole acetic acid (IAA) and
      abscisic acid (ABA), are essential regulators of a multitude of biological
      functions, including plant responses to biotic and abiotic stressors. This study
      set out to determine what hormones might play a role in Pseudomonas fluorescens 
      mediated control of Fusarium head blight (FHB) disease of barley and to determine
      if biocontrol-associated hormones directly affect disease development. RESULTS: A
      previous study distinguished bacterium-responsive genes from bacterium-primed
      genes, distinguished by the fact that the latter are only up-regulated when both
      P. fluorescens and the pathogen Fusarium culmorum are present. In silico analysis
      of the promoter sequences available for a subset of the bacterium-primed genes
      identified several hormones, including IAA and ABA as potential regulators of
      transcription. Treatment with the bacterium or pathogen resulted in increased IAA
      and ABA levels in head tissue; both microbes had additive effects on the
      accumulation of IAA but not of ABA. The microbe-induced accumulation of ABA
      preceded that of IAA. Gene expression analysis showed that both hormones up
      regulated the accumulation of bacterium-primed genes. But IAA, more than ABA up
      regulated the transcription of the ABA biosynthesis gene NCED or the signalling
      gene Pi2, both of which were previously shown to be bacterium-responsive rather
      than primed. Application of IAA, but not of ABA reduced both disease severity and
      yield loss caused by F. culmorum, but neither hormone affect in vitro fungal
      growth. CONCLUSIONS: Both IAA and ABA are involved in the P. fluorescens-mediated
      control of FHB disease of barley. Gene expression studies also support the
      hypothesis that IAA plays a role in the primed response to F. culmorum. This
      hypothesis was validated by the fact that pre-application of IAA reduced both
      symptoms and yield loss asssociated with the disease. This is the first evidence
      that IAA plays a role in the control of FHB disease and in the bacterial priming
      of host defences.

PMID- 23173737
TI  - Therapeutic efficacy of artemether-lumefantrine combination in the treatment of
      uncomplicated malaria among children under five years of age in three ecological
      zones in Ghana.
AB  - BACKGROUND: In 2008, artemether - lumefantrine (AL) and dihydroartemisinin -
      piperaquine (DHAP) were added to artesunate - amodiaquine (AS-AQ) as first-line
      drugs for uncomplicated malaria in Ghana. The introduction of new drugs calls for
      continuous monitoring of these drugs to provide timely information on trends of
      their efficacy and safety to enhance timely evidence-based decision making by the
      National Malaria Control Programme. In this regard, the therapeutic efficacy of
      AL was monitored from September 2010 to April 2011 in four sentinel sites
      representing the three main ecological zones of the country. METHODS: The study
      was a one-arm prospective evaluation of clinical and parasitological responses to
      directly observed treatment for uncomplicated malaria among children aged 6
      months to 59 months using the 2009 WHO protocol for surveillance of anti-malarial
      drug efficacy. Children recruited into the study received weight-based 20/120 mg
      AL at 0, 8, 24, 36, 48, and 60 hrs. Parasitaemia levels were assessed on days 2,
      3, 7, 14, 21, 28, and at any time a study child was brought to the clinic with
      fever. RESULTS: A total of 175 children were enrolled into the study: 56 in the
      savanna zone, 78 in the forest zone and 41 in the coastal zone. Per-protocol
      analysis showed that the overall PCR-corrected cure rates on day 14 and day 28
      were 96.5% (95% CI: 92.1, 98.6) and 95.4% (95% CI: 90.3, 98.0), respectively,
      with statistically significant differences between the ecological zones. The
      90.4% day-28 cure rate observed in the savannah zone (95% CI: 78.2, 96.4) was
      significantly the lowest compared with 100% (95% CI: 93.2, 99.9) in the forest
      zone and 93.8% (95% CI: 77.8, 98.9) in the coastal zone (P = 0.017). Fever and
      parasite clearance were slower among children enrolled in the savannah zone.
      Gametocytaemia after day-3 post-treatment was rare in all the zones. CONCLUSIONS:
      The study has shown that AL remains efficacious in Ghana with significant
      ecologic zonal differences. The savannah zone may be a potential zone for any
      emergence of resistant alleles as a result of the slower parasite clearance
      observed in the zone.

PMID- 23173738
TI  - Use of near-infrared spectroscopy to identify trends in regional cerebral oxygen
      saturation in horses.
AB  - REASONS FOR PERFORMING STUDY: Alterations in cerebral haemodynamics may
      contribute to perianaesthetic complications in horses. Near-infrared spectroscopy
      (NIRS) is frequently used intraoperatively in man to provide information
      regarding cerebral perfusion. OBJECTIVES: To determine whether NIRS can identify
      trends in regional cerebral oxygen saturation (rSO2) in horses and whether there
      is a correlation between rSO2 and venous oxygen tensions. METHODS: A cerebral
      oximeter sensor recorded rSO2 from the dorsal sagittal sinus of 6 healthy horses.
      Values for rSO2, arterial and venous oxygen and carbon dioxide tensions (PaO2,
      PvO2, PaCO2 and PvCO2 respectively), along with arteriovenous oxygen saturations
      (SavO2) were recorded in unsedated (recording period [RP] 1), sedated (RP2) and
      anaesthetised horses (RP3-5) and during recovery (RP6-8). During anaesthesia,
      horses were ventilated to achieve states of normo- (RP3), hyper- (RP4) and
      hypocapnoea (RP5). Data were evaluated descriptively and analysed using linear
      mixed-effects models and Pearson's correlation coefficient. RESULTS: Overall mean
      +/- s.d. values for rSO2, PaO2, PvO2, PaCO2, SavO2 and mean arterial pressure
      varied significantly by RP (P<0.001). Significant decreases in rSO2 were
      identified between RP1 and the post anaesthetic periods (P<0.001). No significant
      differences in rSO2 values were identified between RP1 and the intra-anaesthesia
      periods or between RP3, RP4 and RP5. Significant correlations were identified
      between rSO2 and PaO2 (r = 0.448, P<0.001), rSO2 and PvO2 (r = 0.512, P<0.001)
      and rSO2 and SavO2 (r = 0.469, P<0.001). CONCLUSIONS: This is the first study to
      identify trends in rSO2 in horses using NIRS. A positive correlation was
      identified between rSO2 and PvO2, suggesting that alterations in cerebral
      oxygenation may be reflected in PvO2 . POTENTIAL RELEVANCE: Near-infrared
      spectroscopy may be used to monitor trends in rSO2 during equine anaesthesia.
      Decreasing rSO2 values may act as an early warning signal, alerting clinicians to
      potential cerebral desaturation events and indicating a need for intervention.

PMID- 23173739
TI  - Value of human chorionic gonadotropin levels in diagnosing cervical ectopic
      pregnancy.

PMID- 23173740
TI  - The importance of active learning and practice on the students' mastery of
      pharmacokinetic calculations for the intermittent intravenous infusion dosing of
      antibiotics.
AB  - BACKGROUND: Estimation of pharmacokinetic parameters after intermittent
      intravenous infusion (III) of antibiotics, such as aminoglycosides or vancomycin,
      has traditionally been a difficult subject for students in clinical pharmacology
      or pharmacokinetic courses. Additionally, samples taken at different intervals
      during repeated dose therapy require manipulation of sampling times before
      accurate calculation of the patient-specific pharmacokinetic parameters. The main
      goal of this study was to evaluate the effectiveness of active learning tools and
      practice opportunities on the ability of students to estimate pharmacokinetic
      parameters from the plasma samples obtained at different intervals following
      intermittent intravenous infusion. METHODS: An extensive reading note, with
      examples, and a problem case, based on a patient's chart data, were created and
      made available to students before the class session. Students were required to
      work through the case before attending the class. The class session was devoted
      to the discussion of the case requiring active participation of the students
      using a random participation program. After the class, students were given
      additional opportunities to practice the calculations, using online modules
      developed by the instructor, before submitting an online assignment. RESULTS: The
      performance of students significantly (P < 0.001) improved from a baseline of
      11.3% (pretest) to 60.3% (posttest) after the class discussion. The grades of
      students further improved (P < 0.001) to 89.3% on the take-home assignment after
      they had a chance to study on their own and work on the online practices.
      Finally, students scored 82.6% in a formal mid-term examination, suggesting
      significant retention of the materials. CONCLUSIONS: Despite being a difficult
      subject, students achieve mastery of pharmacokinetic calculations for the topic
      of intermittent intravenous infusion when appropriate active learning strategies
      and practice opportunities are employed.

PMID- 23173741
TI  - Seipin regulates excitatory synaptic transmission in cortical neurons.
AB  - Heterozygosity for missense mutations in Seipin, namely N88S and S90L, leads to a
      broad spectrum of motor neuropathy, while a number of loss-of-function mutations
      in Seipin are associated with the Berardinelli-Seip congenital generalized
      lipodystrophy type 2 (CGL2, BSCL2), a condition that is characterized by severe
      lipoatrophy, insulin resistance, and intellectual impairment. The mechanisms by
      which Seipin mutations lead to motor neuropathy, lipodystrophy, and insulin
      resistance, and the role Seipin plays in central nervous system (CNS) remain
      unknown. The goal of this study is to understand the functions of Seipin in the
      CNS using a loss-of-function approach, i.e. by knockdown (KD) of Seipin gene
      expression. Excitatory post-synaptic currents (EPSCs) were impaired in Seipin-KD
      neurons, while the inhibitory post-synaptic currents (IPSCs) remained unaffected.
      Expression of a shRNA-resistant human Seipin rescued the impairment of EPSC
      produced by Seipin KD. Furthermore, alpha-amino-3-hydroxy-5-methyl-4
      isoxazolepropionic acid (AMPA)-induced whole-cell currents were significantly
      reduced in Seipin KD neurons, which could be rescued by expression of a shRNA
      resistant human Seipin. Fluorescent imaging and biochemical studies revealed
      reduced level of surface AMPA receptors, while no obvious ultrastructural changes
      in the pre-synapse were found. These data suggest that Seipin regulates
      excitatory synaptic function through a post-synaptic mechanism.

PMID- 23173742
TI  - Severe hyponatremia caused by syndrome of inappropriate secretion of antidiuretic
      hormone developed as initial manifestation of human herpesvirus-6-associated
      acute limbic encephalitis after unrelated bone marrow transplantation.
AB  - Severe hyponatremia is a critical electrolyte abnormality in allogeneic stem cell
      transplantation (allo-SCT) recipients and >50% of cases of severe hyponatremia
      are caused by the syndrome of inappropriate secretion of antidiuretic hormone
      (SIADH). Here, we present a patient with rapidly progressive severe hyponatremia
      as an initial sign and symptom of human herpesvirus-6-associated post
      transplantation acute limbic encephalitis (HHV-6 PALE) after allo-SCT. A 45-year
      old woman with acute lymphoblastic leukemia received unrelated bone marrow
      transplantation from a one locus-mismatched donor at the DR locus. On day 21, she
      developed a generalized seizure and loss of consciousness with severe
      hyponatremia, elevated serum antidiuretic hormone (ADH), and decreased serum
      osmolality. A high titer of HHV-6 DNA was detected in cerebrospinal fluid.
      Treatment with foscarnet sodium and hypertonic saline was started with
      improvement of neurological condition within several days. Although an elevated
      serum ADH, low serum osmolality, and high urinary osmolality persisted for 2
      months, she had no other recurrent symptoms of encephalitis. Our experience
      suggests that hyponatremia accompanied by SIADH should be recognized as a
      prodromal or concomitant manifestation of HHV-6 PALE, and close monitoring of
      serum sodium levels in high-risk patients for HHV-6 PALE is necessary for
      immediate diagnosis and treatment initiation.

PMID- 23173744
TI  - Kinetic and in silico analysis of thiazolidin-based inhibitors of alpha-carbonic
      anhydrase isoenzymes.
AB  - Carbonic anhydrases (CAs, EC 4.2.1.1) are inhibited by sulfonamides, inorganic
      anions, phenols, salicylic acid derivatives (acting as drug or prodrugs). A novel
      class of CA inhibitors (CAIs), interacting with the CA isozymes I and II
      (cytosolic) in a different manner, is reported here. Kinetic measurements allowed
      us to identify thiazolidin-based compounds as submicromolar-low micromolar
      inhibitors of these two CA isozymes. Molecular docking studies of a set of such
      inhibitors within CA I and II active site allowed us to understand the inhibition
      mechanism. This new class of inhibitors bind differently compared to other
      classes of inhibitors known to date: they were found between the phenol-binding
      site, filling thus the middle of the enzyme cavity.

PMID- 23173743
TI  - Defective lysosomal proteolysis and axonal transport are early pathogenic events
      that worsen with age leading to increased APP metabolism and synaptic Abeta in
      transgenic APP/PS1 hippocampus.
AB  - BACKGROUND: Axonal pathology might constitute one of the earliest manifestations
      of Alzheimer disease. Axonal dystrophies were observed in Alzheimer's patients
      and transgenic models at early ages. These axonal dystrophies could reflect the
      disruption of axonal transport and the accumulation of multiple vesicles at local
      points. It has been also proposed that dystrophies might interfere with normal
      intracellular proteolysis. In this work, we have investigated the progression of
      the hippocampal pathology and the possible implication in Abeta production in
      young (6 months) and aged (18 months) PS1(M146L)/APP(751sl) transgenic mice.
      RESULTS: Our data demonstrated the existence of a progressive, age-dependent,
      formation of axonal dystrophies, mainly located in contact with congophilic Abeta
      deposition, which exhibited tau and neurofilament hyperphosphorylation. This
      progressive pathology was paralleled with decreased expression of the motor
      proteins kinesin and dynein. Furthermore, we also observed an early decrease in
      the activity of cathepsins B and D, progressing to a deep inhibition of these
      lysosomal proteases at late ages. This lysosomal impairment could be responsible
      for the accumulation of LC3-II and ubiquitinated proteins within axonal
      dystrophies. We have also investigated the repercussion of these deficiencies on
      the APP metabolism. Our data demonstrated the existence of an increase in the
      amyloidogenic pathway, which was reflected by the accumulation of hAPPfl, C99
      fragment, intracellular Abeta in parallel with an increase in BACE and gamma
      secretase activities. In vitro experiments, using APPswe transfected N2a cells,
      demonstrated that any imbalance on the proteolytic systems reproduced the in vivo
      alterations in APP metabolism. Finally, our data also demonstrated that Abeta
      peptides were preferentially accumulated in isolated synaptosomes. CONCLUSION: A
      progressive age-dependent cytoskeletal pathology along with a reduction of
      lysosomal and, in minor extent, proteasomal activity could be directly implicated
      in the progressive accumulation of APP derived fragments (and Abeta peptides) in
      parallel with the increase of BACE-1 and gamma-secretase activities. This retard
      in the APP metabolism seemed to be directly implicated in the synaptic Abeta
      accumulation and, in consequence, in the pathology progression between
      synaptically connected regions.

PMID- 23173745
TI  - Vascular endothelial growth factor and fibroblast growth factor-2 incorporation
      in starch-based bone tissue-engineered constructs promote the in vivo expression
      of neovascularization mediators.
AB  - The ideal bone tissue-engineered (TE) construct remains to be found, although
      daily discoveries significantly contribute to improvements in the field and
      certainly have valuable long-term outcomes. In this work, different TE elements,
      aiming at bone TE applications, were assembled and its effect on the expression
      of several vascularization/angiogenesis mediators analyzed.
      Starch/polycaprolactone (SPCL) scaffolds, obtained by two different
      methodologies, were combined with fibrin sealant (Baxter((r))), human adipose
      derived stem cells (hASCs), and growth factors (vascular endothelial growth
      factor [VEGF] or fibroblast growth factor-2 [FGF-2]), and implanted in vascular
      endothelial growth factor receptor-2 (VEGFR2)-luc transgenic mice. The expression
      of VEGFR2 along the implantation of the designed constructs was followed using a
      luminescence device (Xenogen((r))) and after 2 weeks, the explants were retrieved
      to perform histological analysis and reverse transcriptase-polymerase chain
      reaction for vascularization (VEGF and VEGFR1) and inflammatory (tumor necrosis
      factor-alpha, interleukin-4, and interferon-gamma) markers. It was showed that
      SPCL scaffolds obtained by wet spinning and by fiber bonding constitute an
      adequate support for hASCs. The assembled TE constructs composed by fibrin
      sealant, hASCs, VEGF, and FGF-2 induce only a mild inflammatory reaction after 2
      weeks of implantation. Additionally, the release of VEGF and FGF-2 from the
      constructs enhanced the expression of VEGFR2 and other important mediators in
      neovascularization (VEGF and VEGFR1). These results indicate the potential of
      VEGF or FGF-2 within a bone TE construct composed by wet-spun SPCL, fibrin
      sealant, and hASCs in promoting the vascularization of newly formed tissue.

PMID- 23173746
TI  - An efficient heuristic method for active feature acquisition and its application
      to protein-protein interaction prediction.
AB  - BACKGROUND: Machine learning approaches for classification learn the pattern of
      the feature space of different classes, or learn a boundary that separates the
      feature space into different classes. The features of the data instances are
      usually available, and it is only the class-labels of the instances that are
      unavailable. For example, to classify text documents into different topic
      categories, the words in the documents are features and they are readily
      available, whereas the topic is what is predicted. However, in some domains
      obtaining features may be resource-intensive because of which not all features
      may be available. An example is that of protein-protein interaction prediction,
      where not only are the labels ('interacting' or 'non-interacting') unavailable,
      but so are some of the features. It may be possible to obtain at least some of
      the missing features by carrying out a few experiments as permitted by the
      available resources. If only a few experiments can be carried out to acquire
      missing features, which proteins should be studied and which features of those
      proteins should be determined? From the perspective of machine learning for PPI
      prediction, it would be desirable that those features be acquired which when used
      in training the classifier, the accuracy of the classifier is improved the most.
      That is, the utility of the feature-acquisition is measured in terms of how much
      acquired features contribute to improving the accuracy of the classifier. Active
      feature acquisition (AFA) is a strategy to preselect such instance-feature
      combinations (i.e. protein and experiment combinations) for maximum utility. The
      goal of AFA is the creation of optimal training set that would result in the best
      classifier, and not in determining the best classification model itself. RESULTS:
      We present a heuristic method for active feature acquisition to calculate the
      utility of acquiring a missing feature. This heuristic takes into account the
      change in belief of the classification model induced by the acquisition of the
      feature under consideration. As compared to random selection of proteins on which
      the experiments are performed and the type of experiment that is performed, the
      heuristic method reduces the number of experiments to as few as 40%. Most notable
      characteristic of this method is that it does not require re-training of the
      classification model on every possible combination of instance, feature and
      feature-value tuples. For this reason, our method is far less computationally
      expensive as compared with previous AFA strategies. CONCLUSIONS: The results show
      that our heuristic method for AFA creates an optimal training set with far less
      features acquired as compared to random acquisition. This shows the value of
      active feature acquisition to aid in protein-protein interaction prediction where
      feature acquisition is costly. Compared to previous methods, the proposed method
      reduces computational cost while also achieving a better F-score. The proposed
      method is valuable as it presents a direction to AFA with a far lesser
      computational expense by removing the need for the first time, of training a
      classifier for every combination of instance, feature and feature-value tuples
      which would be impractical for several domains.

PMID- 23173747
TI  - Influence of contact with schizophrenia on implicit attitudes towards
      schizophrenia patients held by clinical residents.
AB  - BACKGROUND: Patients with schizophrenia and their families have suffered greatly
      from stigmatizing effects. Although many efforts have been made to eradicate both
      prejudice and stigma, they still prevail even among medical professionals, and
      little is known about how contact with schizophrenia patients affects their
      attitudes towards schizophrenia. METHODS: We assessed the impact of the renaming
      of the Japanese term for schizophrenia on clinical residents and also evaluated
      the influence of contact with schizophrenia patients on attitudes toward
      schizophrenia by comparing the attitudes toward schizophrenia before and after a
      one-month clinical training period in psychiatry. Fifty-one clinical residents
      participated. Their attitudes toward schizophrenia were assessed twice, before
      and one month after clinical training in psychiatry using the Implicit
      Association Test (IAT) as well as Link's devaluation-discrimination scale.
      RESULTS: The old term for schizophrenia, "Seishin-Bunretsu-Byo", was more
      congruent with criminal than the new term for schizophrenia, "Togo-Shitcho-Sho",
      before clinical training. However, quite opposite to our expectation, after
      clinical training the new term had become even more congruent with criminal than
      the old term. There was no significant correlation between Link's scale and IAT
      effect. CONCLUSIONS: Renaming the Japanese term for schizophrenia still reduced
      the negative images of schizophrenia among clinical residents. However, contact
      with schizophrenia patients unexpectedly changed clinical residents' attitudes
      towards schizophrenia negatively. Our results might contribute to an
      understanding of the formation of negative attitudes about schizophrenia and
      assist in developing appropriate clinical training in psychiatry that could
      reduce prejudice and stigma concerning schizophrenia.

PMID- 23173748
TI  - Hepatic arterial infusion and systemic chemotherapy for breast cancer liver
      metastases.
AB  - Hepatic failure from breast cancer liver metastases (BCLM) is a major cause of
      morbidity and mortality. We reviewed the treatment histories and outcomes of nine
      patients with heavily treated BCLM, who received hepatic arterial infusion (HAI)
      of floxuridine (FUDR)/dexamethasone (Dex) and systemic chemotherapy at our
      institution. Patients received a median of five (range 1-15) HAI treatments.
      There were seven (78%) objective responses. Four patients had grade 3 elevations
      in liver enzymes attributable to HAI. There were no treatment-related deaths.
      Median hepatic and extrahepatic time to progression on HAI were both 6 months.
      Median survival after starting HAI was 17 months (range 1-115). Median overall
      survival from the original breast cancer diagnosis was 110 months (range 52-248).
      One patient is alive with stable disease on systemic therapy alone. HAI and
      systemic chemotherapy is feasible and can benefit selected patients with BCLM,
      who have progressed on prior therapies. Patients require close monitoring for
      treatment-limiting toxicities.

PMID- 23173749
TI  - A new treatment for neurogenic inflammation caused by EV71 with CR2-targeted
      complement inhibitor.
AB  - BACKGROUND: Enterovirus 71 (EV71), one of the most important neurotropic EVs, has
      caused death and long-term neurological sequelae in hundreds of thousands of
      young children in the Asia-Pacific region in the past decade. The neurological
      diseases are attributed to infection by EV71 inducing an extensive peripheral and
      central nervous system (CNS) inflammatory response with abnormal cytokine
      production and lymphocyte depletion induced by EV71 infection. In the absence of
      specific antiviral agents or vaccines, an effective immunosuppressive strategy
      would be valuable to alleviate the severity of the local inflammation induced by
      EV71 infection. PRESENTATION OF THE HYPOTHESIS: The complement system plays a
      pivotal role in the inflammatory response. Inappropriate or excessive activation
      of the complement system results in a severe inflammatory reaction or numerous
      pathological injuries. Previous studies have revealed that EV71 infection can
      induce complement activation and an inflammatory response of the CNS. CR2
      targeted complement inhibition has been proved to be a potential therapeutic
      strategy for many diseases, such as influenza virus-induced lung tissue injury,
      postischemic cerebral injury and spinal cord injury. In this paper, a mouse model
      is proposed to test whether a recombinant fusion protein consisting of CR2 and a
      region of Crry (CR2-Crry) is able to specifically inhibit the local complement
      activation induced by EV71 infection, and to observe whether this treatment
      strategy can alleviate or even cure the neurogenic inflammation. TESTING THE
      HYPOTHESIS: CR2-Crry is expressed in CHO cells, and its biological activity is
      determined by complement inhibition assays. 7-day-old ICR mice are inoculated
      intracranially with EV71 to duplicate the neurological symptoms. The mice are
      then divided into two groups, in one of which the mice are treated with CR2-Crry
      targeted complement inhibitor, and in the other with phosphate-buffered saline. A
      group of mice deficient in complement C3, the breakdown products of which bind to
      CR2, are also infected with EV71 virus. The potential bioavailability and
      efficacy of the targeted complement inhibitor are evaluated by histology,
      immunofluorescence staining and radiolabeling. IMPLICATIONS OF THE HYPOTHESIS:
      CR2-Crry-mediated targeting complement inhibition will alleviate the local
      inflammation and provide an effective treatment for the severe neurological
      diseases associated with EV71 infection.

PMID- 23173750
TI  - Use of a whole-slide imaging system to assess the presence and alteration of
      lymphatic vessels in joint sections of arthritic mice.
AB  - We investigated the presence and alteration of lymphatic vessels in joints of
      arthritic mice using a whole-slide imaging system. Joints and long bone sections
      were cut from paraffin blocks of two mouse models of arthritis: meniscal
      ligamentous injury (MLI)-induced osteoarthritis (OA) and TNF transgene (TNF-Tg)
      induced rheumatoid arthritis (RA). MLI-OA mice were fed a high fat diet to
      accelerate OA development. TNF-Tg mice were treated with lymphatic growth factor
      VEGF-C virus to stimulate lymphangiogenesis. Sections were double
      immunofluorescence stained with anti-podoplanin and alpha-smooth muscle actin
      antibodies. The area and number of lymphatic capillaries and mature lymphatic
      vessels were determined using a whole-slide imaging system and its associated
      software. Lymphatic vessels in joints were distributed in soft tissues mainly
      around the joint capsule, ligaments, fat pads and muscles. In long bones,
      enriched lymphatic vessels were present in the periosteal areas adjacent to the
      blood vessels. Occasionally, lymphatic vessels were observed in the cortical
      bone. Increased lymphatic capillaries, but decreased mature lymphatic vessels,
      were detected in both OA and RA joints. VEGF-C treatment increased lymphatic
      capillary and mature vessel formation in RA joints. Our findings suggest that the
      lymphatic system may play an important role in arthritis pathogenesis and
      treatment.

PMID- 23173751
TI  - GERD in elderly patients: surgical treatment with Nissen-Rossetti laparoscopic
      technique, outcome.
AB  - BACKGROUND: The gastro-esophageal reflux disease (GERD) is one of the most
      frequent disease of the upper gastro-entheric tract. Surgical treatment is
      reserved to selected patients, affected by severe forms of disease and/or without
      compliance to medical therapy.In 95%-60% of the patients submitted to surgical
      antireflux intervention, a notable improvement of the quality of life is
      observed.Functional evaluations performed on pre and post--surgical pHmetric and
      manometric examination have provided new acquisitions about improvements in the
      restoration of anatomical and functional integrity of the esophagus-gastric
      antireflux barrier. METHODS: 45 elderly patients with GERD were recruited in a 27
      months period. All patients were subjected to laparoscopic Nissen-Rossetti 360
      degrees  fundoplication. The subjects had a pre-surgical evaluation with:* 24
      hours pHmetry,* esophageal manometry,The same evaluation was repeated 1 month and
      6 months after surgical intervention. RESULTS: In our series all patients get
      benefit from surgical treatment, with an improvement of pHmetric and manometric
      parameters and a regression of complications of GERD such as Barrett's
      metaplasia. In 8.33% of patients a PPI therapy was necessary, after the surgical
      intervention, to control symptoms. CONCLUSIONS: The role of surgery in GERD
      concerns selected patients. Nissen-Rossetti mini-invasive approach is performed
      with an acceptable percentage of complications (3%-10%). This technique is
      associated with a good control of GERD symptoms in a short and middle term and
      with an improvement of functional parameters, such as pHmetric and manometric.

PMID- 23173752
TI  - Top topics in HCV research arena.
AB  - A significant improvement in the rate of eradication of Hepatitis C Virus
      Genotype 1 has been achieved with the addition of Boceprevir and Telaprevir to
      pegylated interferon and ribavirin. These two drugs are the heralds of a new wave
      of antivirals that will improve the efficacy of pegylated interferon or even will
      substitute this drug in interferon free combinations. The results of phase II
      studies in patients naive to treatment seem to be very promising strongly
      supporting the possibility of a large success for a first line all oral antiviral
      combination in interferon naive. However, data observed in interferon experienced
      patients are less exciting and probably more complex treatment regimens will be
      needed to treat this patients' population.

PMID- 23173753
TI  - Assessing the cost-effectiveness of treating chronic hepatitis C virus in people
      who inject drugs in Australia.
AB  - BACKGROUND AND AIM: To assess the cost-effectiveness of hepatitis C virus
      treatment with pegylated interferon alfa-2a and ribavirin in current and former
      people who inject drugs (PWID). METHODS: A decision analytic model simulated the
      lifetime costs and outcomes of four treatment options: early treatment with mild
      fibrosis, standard treatment with moderate fibrosis, late treatment with
      compensated cirrhosis, and no treatment. Treatment modalities were simulated
      across current, former, and never-injector cohorts of 1000 hypothetical patients
      with chronic hepatitis C virus. The main outcome measures were incremental costs
      ($AUD) per quality-adjusted life years (QALYs) gained, and incremental cost
      effectiveness ratios (ICERs) were calculated for each cohort. RESULTS: Treatment
      of current PWID during mild fibrosis resulted in a discounted average gain of
      1.60 QALYs (95% confidence interval 0.93-2.26) for an added cost of $12,723
      ($11,153-$14,396) compared with no treatment, yielding an ICER of $7941 per QALY
      gained ($6347-$12,017). Former PWID gained 1.80 QALYs (1.29-2.33) for $10,441
      ($8843-$12,074) for early treatment compared with no treatment, resulting in an
      ICER of $5808 per QALY gained ($5189-$6849). Never-injectors gained 2.33 QALYs
      (1.87-2.80) for $9290 ($7642-$10,912) compared with no treatment-an ICER of $3985
      per QALY gained ($3896-$4080). Early treatment was more cost-effective than late
      treatment in all cohorts. CONCLUSIONS: Despite comorbidities, increased
      mortality, and reduced adherence, treatment of both current and former PWID is
      cost-effective. Our estimates fall below the unofficial Australian cost
      effectiveness threshold of $AUD 50,000 per QALY for public subsidies. Scaling up
      treatment for PWID can be justified on purely economic grounds.

PMID- 23173754
TI  - Adolescent gain in positive valence of a socially relevant stimulus: engagement
      of the mesocorticolimbic reward circuitry.
AB  - A successful transition from childhood to adulthood requires adolescent
      maturation of social information processing. The neurobiological underpinnings of
      this maturational process remain elusive. This research employed the male Syrian
      hamster as a tractable animal model for investigating the neural circuitry
      involved in this critical transition. In this species, adult and juvenile males
      display different behavioral and neural responses to vaginal secretions, which
      contain pheromones essential for expression of sexual behavior in adulthood.
      These studies tested the hypothesis that vaginal secretions acquire positive
      valence over adolescent development via remodeling of neural circuits underlying
      sexual reward. Sexually naive adult, but not juvenile, hamsters showed a
      conditioned place preference for vaginal secretions. Differences in behavioral
      response to vaginal secretions between juveniles and adults correlated with a
      difference in the vaginal secretion-induced neural activation pattern in
      mesocorticolimbic reward circuitry. Fos immunoreactivity increased in response to
      vaginal secretions in the medial amygdala and ventral tegmental dopaminergic
      cells of both juvenile and adult males. However, only in adults was there a Fos
      response to vaginal secretions in non-dopaminergic cells in interfascicular
      ventral tegmental area, nucleus accumbens core and infralimbic medial prefrontal
      cortex. These results demonstrate that a socially relevant chemosensory stimulus
      acquires the status of an unconditioned reward during adolescence, and that this
      adolescent gain in social reward is correlated with experience-independent
      engagement of specific cell groups in reward circuitry.

PMID- 23173755
TI  - Comparative study between Levobupivacaine and Bupivacaine for hernia surgery in
      the elderly.
AB  - BACKGROUND: The inguinal hernia is one of the most common diseases in the
      elderly. Treatment of this type of pathology is exclusively surgical and relies
      almost always on the use of local anesthesia. While in the past hernia surgery
      was carried out mainly by general anesthesia, in recent years there has been
      growing emphasis on the role of local anesthesia. METHODS: The aim of our study
      was to compare intra-and postoperative analgesia obtained by the use of
      levobupivacaine compared with that of bupivacaine. Bupivacaine is one of the main
      local anesthetics used in the intervention of inguinal hernioplasty.
      Levobupivacaine is an enantiomer of racemic bupivacaine with less cardiotoxicity
      and neurotoxicity. The study was conducted from April 2010 to May 2012. We
      collected data of forty male patients, aged between 73 and 85 years, who
      underwent inguinal hernioplasty with local anesthesia for the first time.
      RESULTS: Minimal pain is the same in both groups. Mild pain was more frequent in
      the group who used bupivacaine, moderate pain was slightly more frequent in the
      group who used levobupivacaine, and the same for intense pain. It is therefore
      evident how Bupivacaine is slightly less preferred after four and twenty four
      hours, while the two drugs seem to have the same effect at a distance of twelve
      and forty-eight hours. Bupivacaine shows a significantly higher number of
      complications, as already demonstrated by previous studies. The request for an
      analgesic was slightly higher in patients receiving levobupivacaine. CONCLUSIONS:
      After considering all these elements, we can conclude that the clinical efficacy
      of levobupivacaine and racemic bupivacaine are essentially similar, when used
      under local intervention of inguinal hernioplasty.

PMID- 23173756
TI  - Alterations in ventricular K(ATP)  channel properties during aging.
AB  - Coronary heart disease remains the principle cause of mortality in the United
      States. During aging, the efficiency of the cardiovascular system is decreased
      and the aged heart is less tolerant to ischemic injury. ATP-sensitive K(+)
      (K(ATP)) channels protect the myocardium against ischemic damage. We investigated
      how aging affects cardiac K(ATP) channels in the Fischer 344 rat model.
      Expression of K(ATP) channel subunit mRNA and protein levels was unchanged in
      hearts from 26-month-old vs. 4-month-old rats. Interestingly, the mRNA expression
      of several other ion channels (> 80) was also largely unchanged, suggesting that
      posttranscriptional regulatory mechanisms occur during aging. The whole-cell
      K(ATP) channel current density was strongly diminished in ventricular myocytes
      from aged male rat hearts (also observed in aged C57BL/6 mouse myocytes).
      Experiments with isolated patches (inside-out configuration) demonstrated that
      the K(ATP) channel unitary conductance was unchanged, but that the inhibitory
      effect of cytosolic ATP on channel activity was enhanced in the aged heart. The
      mean patch current was diminished, consistent with the whole-cell data. We
      incorporated these findings into an empirical model of the K(ATP) channel and
      numerically simulated the effects of decreased cytosolic ATP levels on the human
      action potential. This analysis predicts lesser activation of K(ATP) channels by
      metabolic impairment in the aged heart and a diminished action potential
      shortening. This study provides insights into the changes in K(ATP) channels
      during aging and suggests that the protective role of these channels during
      ischemia is significantly compromised in the aged individual.

PMID- 23173757
TI  - Antidepressant use, depression, and new-onset diabetes among elderly Medicare
      beneficiaries.
AB  - BACKGROUND: The aim of the present study was to examine the association between
      antidepressant use, diagnosed depression, and new-onset diabetes among elderly
      Medicare beneficiaries. METHODS: Longitudinal data from merged survey and claims
      from the nationally representative Medicare Current Beneficiary Survey(MCBS) from
      1999 to 2005 were used. Diabetes incidence was extracted from claims and survey
      data over a 3-year period. Data regarding depression and antidepressant use over
      time were obtained. Multivariate logistic regression analysis was used to examine
      associations between antidepressant use, depression, and new-onset diabetes,
      adjusted for demographic, socioeconomic, and lifestyle risk factors. Analyses
      accounted for the complex design of the MCBS. RESULTS: The incident diabetes rate
      was 4.8% for those "without depression and without antidepressants" and 9.5% for
      those with any antidepressant use in all 3 years and diagnosed depression".
      Compared with Medicare beneficiaries who did not report any antidepressant use,
      beneficiaries reporting antidepressant use in all 3 years were 50% more likely to
      have new-onset diabetes. However, when diagnosed depression was entered in the
      model, there was no significant association between long-term antidepressant use
      and new-onset diabetes. Medicare beneficiaries with any depression were twice as
      likely as those without depression to develop diabetes (adjusted odds ratio 2.04;
      95% confidence interval 1.51, 2.75). CONCLUSIONS: Depression independently
      increased the risk of developing diabetes in the MCBS population, although there
      is no evidence of an association between antidepressant use and new-onset
      diabetes. If replicated, these results have significant clinical implications.

PMID- 23173758
TI  - Aspiration pneumonia in patients treated with radiotherapy for head and neck
      cancer.
AB  - Aspiration and aspiration pneumonia has been reported with a high incidence in
      head and neck cancer populations treated with chemo-radiotherapy. The aim of this
      study was to investigate the incidence and mortality of aspiration pneumonia in
      an unselected series of head and neck cancer patients treated with curative
      radiotherapy with or without concurrent weekly cisplatin. MATERIAL AND METHODS: A
      total of 324 consecutive patients treated with curative intended radiotherapy for
      head and neck cancer in a single Danish referral center in Aarhus from 2006 to
      2008 were included and followed for a median of 4.3 years. Data on patient, tumor
      and treatment characteristics were obtained from the DAHANCA database. Data on
      hospital admissions were obtained from the National Patient Registry. Data from
      the National Registry of Causes of Death were obtained on all deaths and causes
      of death. RESULTS: Severe dysphagia occurred in 32% of the 324 patients included.
      A total of 18 patients developed aspiration pneumonia, corresponding to an
      incidence rate of 29 (95% CI 17-46) per 1000 person-years and an incidence
      proportion of 5.3% (95% CI 3.1-8.3%) in the first year after radiotherapy;
      significant risk factors included tube feeding, clinical stage, severe dysphagia
      and incomplete response to treatment. Three of the 18 patients with aspiration
      pneumonia died from this complication. CONCLUSION: Dysphagia-related aspiration
      and aspiration pneumonia are serious and potentially fatal treatment
      complications to accelerated radiotherapy, but occur less frequent than
      previously reported.

PMID- 23173759
TI  - A randomised controlled trial to improve general practitioners' services in
      cancer rehabilitation: effects on general practitioners' proactivity and on
      patients' participation in rehabilitation activities.
AB  - Few studies have evaluated initiatives targeting implementation of cancer
      rehabilitation. In this study we aim to test the effects of a complex
      intervention designed to improve general practitioners' (GPs) involvement in
      cancer rehabilitation. Outcomes were proactive contacts to patients by their GP
      reported by the patients and GPs, respectively, and patients' participation in
      rehabilitation activities. METHODS: Cluster randomised controlled trial. All
      general practices in Denmark were randomised to an intervention group or to a
      control group (usual procedures). Patients were subsequently allocated to the
      intervention or the control group based on randomisation status of their GP.
      Between May 2008 and February 2009, adult patients treated for incident cancer at
      Vejle Hospital, Denmark, were assessed for eligibility. A total of 323 general
      practices were included, allocating 486 patients to an intervention and 469 to a
      control group. The intervention included a patient interview about rehabilitation
      with a rehabilitation coordinator at the hospital, comprehensive information to
      the GP about individual needs for rehabilitation, and an encouragement to the GP
      to contact the patient proactively. Questionnaires were administered to patients
      and GPs at 14 months after inclusion. RESULTS: At baseline average age of
      patients was 63 years and 72% were female. The most frequent cancer localisations
      were breast (43%), lung (15%), and malignant melanoma (8%). The intervention had
      no effect on either patient- or GP-reported extent of GP proactivity. Further, no
      effect was observed on patient participation in rehabilitation activities during
      the 14-month follow-up period. DISCUSSION: The intervention had no effect on GP
      proactivity or on patient participation in rehabilitation activities. However,
      analyses showed a significant association between proactivity and participation
      and we, therefore, conclude that increased GP proactivity may facilitate patient
      participation in rehabilitation activities.

PMID- 23173760
TI  - Ewing's sarcoma family of tumors in Finland during 1990-2009: a population-based
      study.
AB  - BACKGROUND: Ewing's sarcoma family of tumors (ESFTs) are rare bone and soft
      tissue tumors characterized by specific genetic alterations. Our aim was to carry
      out a nationwide analysis of ESFT, to survey the treatments used and to report
      the five-year disease specific and event-free survival rates (EFS and DSS).
      MATERIAL AND METHODS: The study data was gathered from the Finnish National
      Cancer Registry and all five University Hospitals and consisted of 76 bone and
      soft tissue ESFT patients diagnosed during 1990-2009. Their medical records were
      reviewed and data on their disease, treatments, complications and outcome were
      analyzed. RESULTS: The five-year EFS and DSS of patients with localized disease
      at diagnosis (n = 57) were 70% and 60%, respectively. Factors contributing to DSS
      and EFS were the axial vs. peripheral site of primary tumor and adequate surgical
      resection of the primary tumor. DSS was also affected by patient's age at
      diagnosis and the treatment employed. The five-year DSS of patients with
      metastatic disease at diagnosis (n = 19) was 33% and both preoperative and high
      dose chemotherapy were associated with improved survival. CONCLUSION: Population
      based studies including both bone and soft tissue ESFTs are few. In this
      nationwide, population-based study on Finnish bone and soft tissue ESFT patients,
      we find their treatment successful and results comparable to those previously
      published. Absence of metastases, young age at diagnosis and a peripheral primary
      tumor site were associated with a better prognosis. It seems that surgical
      resection of the primary tumor should be performed whenever adequate resection
      margins can be achieved. The role of high dose chemotherapy merits further
      studies in this setting.

PMID- 23173761
TI  - Polycystic ovary syndrome in Salvador, Brazil: a prevalence study in primary
      healthcare.
AB  - BACKGROUND: Polycystic ovary syndrome (PCOS) is a common condition in women of
      reproductive age. It is characterized by hyperandrogenism,
      oligomenorrhea/amenorrhea and polycystic ovaries. It is associated with obesity,
      diabetes, dyslipidemia and cardiovascular disease. No studies have been conducted
      on the prevalence of PCOS in Brazilian or South American women. Few studies using
      the Rotterdam criteria have been published. The objective of the present study
      was to calculate the prevalence of PCOS at primary healthcare level in Salvador,
      Brazil based on these criteria. METHODS: This was a cross-sectional, two-phase
      study conducted in a probability sample of women of 18-45 years of age screened
      for cervical cancer in the primary healthcare network of the city of Salvador,
      Brazil. In the first phase, interviews were conducted, weight, height, waist
      circumference, blood pressure and random blood sugar levels were measured, and
      the presence of acne and hirsutism was investigated. Women with at least one
      diagnostic criterion were referred for the second phase, which consisted of
      specialist consultation, pelvic ultrasonography and hormone measurements for
      differential diagnosis and/or investigation of a second criterion. RESULTS: Of
      the 859 women interviewed, 88.5% were black and 58.7% had 11 years of schooling
      or less. A diagnosis of PCOS was excluded in 84.4%, undetermined in 7.1% and
      confirmed in 8.5% (95% CI: 6.80-10.56). There were no statistically significant
      differences between these three groups with respect to weight, body mass index,
      waist circumference, blood sugar levels or arterial blood pressure. Women with
      PCOS were younger (p = 0.00), taller (p = 0.04), had fewer children (p = 0.00),
      were better educated (p = 0.01), and had higher total testosterone levels (p =
      0.01) and a higher LH/FSH ratio (p = 0.01). CONCLUSION: According to the
      Rotterdam criteria, the prevalence of PCOS in women seeking primary healthcare in
      Salvador, Brazil, was 8.5%.

PMID- 23173762
TI  - Study on bending behaviour of nickel-titanium rotary endodontic instruments by
      analytical and numerical analyses.
AB  - AIM: To develop analytical models and analyse the stress distribution and
      flexibility of nickel-titanium (NiTi) instruments subject to bending forces.
      METHODOLOGY: The analytical method was used to analyse the behaviours of NiTi
      instruments under bending forces. Two NiTi instruments (RaCe and Mani NRT) with
      different cross-sections and geometries were considered. Analytical results were
      derived using Euler-Bernoulli nonlinear differential equations that took into
      account the screw pitch variation of these NiTi instruments. In addition, the
      nonlinear deformation analysis based on the analytical model and the finite
      element nonlinear analysis was carried out. Numerical results are obtained by
      carrying out a finite element method. RESULTS: According to analytical results,
      the maximum curvature of the instrument occurs near the instrument tip. Results
      of the finite element analysis revealed that the position of maximum von Mises
      stress was near the instrument tip. Therefore, the proposed analytical model can
      be used to predict the position of maximum curvature in the instrument where
      fracture may occur. Finally, results of analytical and numerical models were
      compatible. CONCLUSION: The proposed analytical model was validated by numerical
      results in analysing bending deformation of NiTi instruments. The analytical
      model is useful in the design and analysis of instruments. The proposed
      theoretical model is effective in studying the flexibility of NiTi instruments.
      Compared with the finite element method, the analytical model can deal
      conveniently and effectively with the subject of bending behaviour of rotary NiTi
      endodontic instruments.

PMID- 23173763
TI  - Assessment of left ventricular geometrical patterns and function among
      hypertensive patients at a tertiary hospital, Northern Tanzania.
AB  - BACKGROUND: With hypertension, the cardiovascular system changes to adapt to the
      varying neuro-humoral and hemodynamic changes and this may lead to the
      development of different left ventricular geometric patterns, each carrying a
      different risk profile for major adverse cardiovascular events. METHODS: Using a
      consecutive sampling technique, a cross-sectional, prospective, hospital based
      study was done and two hundred and twenty seven (227) hypertensive patients were
      studied. RESULTS: The distribution of different abnormal LV geometrical patterns
      was 19.8%, 28.2%, 22% for concentric remodelling, concentric hypertrophy and
      eccentric hypertrophy respectively. With echocardiographic criteria, the
      proportion of patients with left ventricular hypertrophy (LVH) was higher when
      left ventricular mass (LVM) was indexed to height(2.7) than to body surface area
      (70.0% vs. 52.9%). Duration of hypertension markedly influenced the type of LV
      geometry with normal LV geometry predominating in early hypertension and abnormal
      geometrical patterns predominating in late hypertension. The left ventricular
      fractional shortening decreased with duration of hypertension and was common in
      patients with eccentric hypertrophy. Age of the patient, systolic blood pressure,
      duration of hypertension and body mass index were found to be independent
      predictors left ventricular hypertrophy. CONCLUSION: About 70% of hypertensive
      patients had abnormal geometry existing in different patterns. Eccentric
      hypertrophy had more of clinical and echocardiographic features suggestive of
      reduced left ventricular systolic function. Hypertensive patients should be
      recognized as a heterogeneous population and therefore stratifying them into
      their respective LV geometrical patterns is useful as way of assessing their risk
      profile as well as instituting appropriate management.

PMID- 23173764
TI  - Treatment of a rapidly expanding thoracoabdominal aortic aneurysm after
      endovascular repair of descending thoracic aortic aneurysm in an old patient.
AB  - BACKGROUND: Aortic pathology progression and/or procedure related complications
      following endovascular repair should always be considered mostly in older
      patients. We herein describe a hybrid procedure for treatment of rapidly
      expanding thoracoabdominal aneurysm following endovascular treatment of a
      descending thoracic aortic aneurysm in an older patient. CASE PRESENTATION: A 82
      year-old man at 18 months after endovascular surgery for a contained rupture of
      descending thoracic aortic aneurysm revealed a type IV thoracoabdominal aneurysm
      with significant increase of the aortic diameters at superior mesenteric and
      renal artery levels. A hybrid approach consisting of preventive visceral vessel
      revascularization and endovascular repair of entire abdominal aorta was
      performed. Under general anaesthesia and by xyphopubic laparotomy, the infrarenal
      aneurysmatic aorta and common iliac arteries were replaced by a bifurcated woven
      prosthetic graf. From each of the prosthetic branches two reverse 14 x 7 mm
      bifurcated PTFE prosthetic grafts were anastomized to both renal arteries and to
      the celiac axis and superior mesenteric artery, respectively. Vessel ischemia was
      restricted to the time required for anastomosis. Three 10 cm Gore endovascular
      stent-grafts for a total length of 15 cm, were used. The overlapping of the stent
      grafts was carried out from the bottom upwards, starting from the aorto-iliac
      prosthetic body up to the healthy segment of thoracic aorta, 40 mm from the
      previous stent-grafts.The patient was discharged on the 9th postoperative day.
      CONCLUSION: This technique offers the advantage of a less invasive treatment,
      reducing the risk of paraplegia, visceral ischaemia and pulmonary complications,
      mostly in older patients.

PMID- 23173765
TI  - Morbidity and mortality due to malaria in Est Mono district, Togo, from 2005 to
      2010: a times series analysis.
AB  - BACKGROUND: In 2004, Togo adopted a regional strategy for malaria control that
      made use of insecticide-treated nets (ITNs), followed by the use of rapid
      diagnostic tests (RDTs), artemisinin-based combination therapy (ACT). Community
      health workers (CHWs) became involved in 2007. In 2010, the impact of the
      implementation of these new malaria control strategies had not yet been
      evaluated. This study sought to assess the trends of malaria incidence and
      mortality due to malaria in Est Mono district from 2005 to 2010. METHODS:
      Secondary data on confirmed and suspected malaria cases reported by health
      facilities from 2005 to 2010 were obtained from the district health information
      system. Rainfall and temperature data were provided by the national Department of
      Meteorology. Chi square test or independent student's t-test were used to compare
      trends of variables at a 95% confidence interval. An interrupted time series
      analysis was performed to assess the effect of meteorological factors and the use
      of ACT and CHWs on morbidity and mortality due to malaria. RESULTS: From January
      2005 to December 2010, 114,654 malaria cases (annual mean 19,109 +/- 6,622) were
      reported with an increase of all malaria cases from 10,299 in 2005 to 26,678
      cases in 2010 (p<0.001). Of the 114,654 malaria cases 52,539 (45.8%) were
      confirmed cases. The prevalence of confirmed malaria cases increased from 23.1
      per 1,000 in 2005 to 257.5 per 1,000 population in 2010 (p <0.001). The mortality
      rate decreased from 7.2 per 10,000 in 2005 to 3.6 per 10,000 in 2010 (p <0.001),
      with a significant reduction of 43.9% of annual number of death due to malaria.
      Rainfall (beta-coefficient = 1.6; p = 0.05) and number of CHWs trained (beta
      coefficient = 6.8; p = 0.002) were found to be positively correlated with malaria
      prevalence. CONCLUSION: This study showed an increase of malaria prevalence
      despite the implementation of the use of ACT and CHW strategies. Multicentre data
      analysis over longer periods should be carried out in similar settings to assess
      the impact of malaria control strategies on the burden of the disease. Integrated
      malaria vector control management should be implemented in Togo to reduce malaria
      transmission.

PMID- 23173766
TI  - Surgical lesions of the small colon and post operative survival in a UK hospital
      population.
AB  - REASONS FOR PERFORMING STUDY: There is limited information about risk factors and
      survival associated with disorders of the small colon requiring surgical
      management. OBJECTIVES: 1) To document the types of surgical lesion in horses
      where pathology of the small (descending) colon was the primary cause of
      abdominal pain, 2) to describe the short- and long-term survival of these cases
      and identify factors associated with survival and 3) to identify preoperative
      variables associated with localisation of a lesion to the small colon. METHODS:
      Clinical data and long-term follow-up were obtained for horses that underwent
      exploratory laparotomy over a 10-year period. Descriptive data were generated for
      short- and long-term survival and survival analysis performed to identify factors
      associated with reduced survival. Univariable and multivariable relationships
      were explored using a Cox proportional hazards model. Preoperative factors
      associated with increased likelihood of a small colon lesion were explored, using
      controls randomly selected from horses undergoing exploratory laparotomy for
      treatment of colic unrelated to the small colon. RESULTS: The study population
      included 84 horses. Of horses with small colon lesions recovered from
      anaesthesia, the percentage that survived until discharge, one year and 2 years
      following surgery, was 91.0, 81.0 and 73.5%, respectively. Median survival time
      for horses in which a resection had been performed was 1029 vs. 3072 days in the
      nonresection group. Small colon cases were more likely to have shown a longer
      duration of colic signs prior to admission (P<0.001) and to develop post
      operative diarrhoea (P = 0.001) when compared with surgical controls.
      CONCLUSIONS: Lesions of the small colon carry a good prognosis for survival
      following surgery. Resection and anastomosis was the only factor associated with
      reduced long-term survival. POTENTIAL RELEVANCE: This study provides information
      about lesion types and post operative survival that may be used to assist
      informed decision-making when managing these cases.

PMID- 23173767
TI  - Structural and functional characterization of mycobactericidal ubiquitin-derived
      peptides in model and bacterial membranes.
AB  - The mycobactericidal properties of macrophages include the delivery of bacteria
      to a hydrolytic lysosome enriched in bactericidal ubiquitin-derived peptides (Ub
      peptides). To improve our understanding of interactions of ubiquitin-derived
      peptides with mycobacteria, we further characterized the structure and function
      of bactericidal Ub-peptide Ub2. We found that Ub2 adopts a beta-sheet
      conformation in the context of sodium dodecyl sulfate micelles and phospholipid
      (1:1 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoglycerol/1-palmitoyl-2-oleoyl-sn
      glycero-3-phosphatidylcholine) vesicles that was dependent upon the primary
      sequence of the peptide. Point mutations in Ub2 that reduced the net charge of
      the peptide decreased Ub2 bactericidal activity. We investigated Ub-peptide
      function in the context of model membranes and intact bacteria. Differential
      scanning calorimetry analysis demonstrated that Ub2 inserts into and perturbs
      model phospholipid vesicles. In addition, we demonstrate that Ub2 disrupts the
      integrity of the mycobacterial membrane, equilibrates the transmembrane
      potential, and is localized within both the mycobacterial membrane and cytoplasm
      of treated bacteria. Finally, we identified additional bactericidal Ub-peptides
      and characterized their activity and structure. This study provides new insight
      into the mycobactericidal mechanisms of Ub-peptides.

PMID- 23173768
TI  - Inflammatory mechanisms of ventilator-induced lung injury: a time to stop and
      think?
AB  - Ventilator-induced lung injury (VILI) is the phenomenon by which mechanical
      ventilation exacerbates lung injury in critically ill patients. It is
      particularly relevant for those suffering from acute respiratory distress
      syndrome, in which the iatrogenic injury caused by VILI contributes to their high
      mortality. The innate immune system is widely accepted to play an important role
      during VILI. However, it is our belief that the identification of inflammatory
      mediators that are crucial during VILI, and thus may make useful therapeutic
      targets, has become obscured by the wide variety of pre-clinical animal models of
      VILI reported in the literature. We aim here to summarise some of our work
      addressing this issue over the last 10 years, and thus, we hope, make
      interpretation of a convoluted field a little clearer.

PMID- 23173769
TI  - Outside enclosure and additional enrichment for dairy goats--a preliminary study.
AB  - BACKGROUND: Dairy goats are commonly housed at a space allowance of 0.7-0.8
      m2/goat in commercial Norwegian goat herds, which is very low compared to
      regulations and recommendations in other European countries. One easy and cheap
      way to increase space allowance is to allow the animals' access to outdoor area.
      The aim of this study was to investigate the effect of access to an outside
      enclosure and environmental enrichment for dairy goats kept in slatted floor pens
      with low space allowance on their activity pattern and social behaviour. METHODS:
      A group of 82 dairy goats on a commercial Norwegian dairy farm were kept inside
      during the winter period from October to April. In April the goats were given
      access to an outside enclosure for 8 hours per day. After having access to the
      enclosure for another for two days, enrichment (branches) was provided, and after
      19 days the enrichment were removed. The goats were observed for 5 hours per day
      for the two last days before they got access to the outside enclosure, the two
      days in the enclosure, the two first and the two last days with enrichment and
      for the following two days without enrichment by two trained observers. RESULTS:
      When allowed access to the enclosure, the goats spent nearly 50% of the time
      outside, and later the time spent outside was reduced to less than 40% (P <
      0.0001), but there was no clear effect of enrichment. All the goats appeared to
      have a regular use of the enclosure. Time spent resting decreased 59.2% to only
      25.2% when the goats first got access to the enclosure, but then started to
      increase again (P < 0.0001). Initially time spent exploring and chewing the
      branches was 20%, but this was reduced to around 12% in the last part of the
      ENRICH period (P < 0.0001). Number of aggressive interactions tended to increase
      when the goats were allowed access to the outdoor enclosure whereas play
      behaviour was only observed in the outside enclosure (P < 0.05). CONCLUSIONS: In
      conclusion, the goats preferred to use the outside enclosure when being active,
      and branches were perceived as an attractive enrichment.

PMID- 23173770
TI  - Attitudes toward statistics in medical postgraduates: measuring, evaluating and
      monitoring.
AB  - BACKGROUND: In medical training, statistics is considered a very difficult course
      to learn and teach. Current studies have found that students' attitudes toward
      statistics can influence their learning process. Measuring, evaluating and
      monitoring the changes of students' attitudes toward statistics are important.
      Few studies have focused on the attitudes of postgraduates, especially medical
      postgraduates. Our purpose was to understand current attitudes regarding
      statistics held by medical postgraduates and explore their effects on students'
      achievement. We also wanted to explore the influencing factors and the sources of
      these attitudes and monitor their changes after a systematic statistics course.
      METHODS: A total of 539 medical postgraduates enrolled in a systematic statistics
      course completed the pre-form of the Survey of Attitudes Toward Statistics -28
      scale, and 83 postgraduates were selected randomly from among them to complete
      the post-form scale after the course. RESULTS: Most medical postgraduates held
      positive attitudes toward statistics, but they thought statistics was a very
      difficult subject. The attitudes mainly came from experiences in a former
      statistical or mathematical class. Age, level of statistical education, research
      experience, specialty and mathematics basis may influence postgraduate attitudes
      toward statistics. There were significant positive correlations between course
      achievement and attitudes toward statistics. In general, student attitudes showed
      negative changes after completing a statistics course. CONCLUSIONS: The
      importance of student attitudes toward statistics must be recognized in medical
      postgraduate training. To make sure all students have a positive learning
      environment, statistics teachers should measure their students' attitudes and
      monitor their change of status during a course. Some necessary assistance should
      be offered for those students who develop negative attitudes.

PMID- 23173771
TI  - Effect of antioxidant supplementation on the total yield, oxidative stress
      levels, and multipotency of bone marrow-derived human mesenchymal stromal cells.
AB  - Bone marrow-derived multipotent mesenchymal stromal cells (MSCs) are the most
      frequently investigated cell type for potential regenerative strategies because
      they are relatively easy to isolate and are able to differentiate into several
      mesenchymal lineages. Unfortunately, during ex vivo culture, MSCs present gradual
      loss of differentiation potential and reduced clinical efficacy. Reactive oxygen
      species (ROS) are associated with oxidative damage and accumulate during MSC
      expansion. Because ROS are believed to be involved in the loss of multipotency,
      we hypothesized that compounds with antioxidant activity have the capacity to
      scavenge ROS, prevent cellular damage, and rescue culture-induced loss of
      multipotency. In this manuscript, we show that antioxidant supplementation can
      partially rescue the loss of alkaline phosphatase expression induced by oxidizing
      agents and increases the yield of hMSCs, when supplemented to a fresh bone marrow
      aspirate. Concomitantly, oxidative DNA damage and ROS levels in hMSCs were
      reduced by antioxidants. We conclude that antioxidant supplementation during MSC
      expansion reduces the DNA damage load and increases the MSC yield.

PMID- 23173773
TI  - Analysis of the pathological severity degree of aortic stenosis (AS) and mitral
      stenosis (MS) using the discrete wavelet transform (DWT).
AB  - The heart is the principal organ that circulates blood. In normal conditions it
      produces four sounds for each cardiac cycle. However, most often only two sounds
      appear essential: S1 and S2. Two other sounds: S3 and S4, with lower amplitude
      than S1 or S2, appear occasionally in the cardiac cycle by the effect of disease
      or age. The presence of abnormal sounds in one cardiac cycle provide valuable
      information on various diseases. The aortic stenosis (AS), as being a valvular
      pathology, is characterized by a systolic murmur due to a narrowing of the aortic
      valve. The mitral stenosis (MS) is characterized by a diastolic murmur due to a
      reduction in the mitral valve. Early screening of these diseases is necessary;
      it's done by a simple technique known as: phonocardiography. Analysis of
      phonocardiograms signals using signal processing techniques can provide for
      clinicians useful information considered as a platform for significant decisions
      in their medical diagnosis. In this work two types of diseases were studied:
      aortic stenosis (AS) and mitral stenosis (MS). Each one presents six different
      cases. The application of the discrete wavelet transform (DWT) to analyse
      pathological severity of the (AS and MS was presented. Then, the calculation of
      various parameters was performed for each patient. This study examines the
      possibility of using the DWT in the analysis of pathological severity of AS and
      MS.

PMID- 23173772
TI  - Epidemiology, risk factors, and outcomes of Clostridium difficile infection in
      kidney transplant recipients.
AB  - BACKGROUND: We sought to describe the epidemiology and risk factors for
      Clostridium difficile infection (CDI) among kidney transplant recipients (KTR)
      between 1 January 2008 and 31 December 2010. METHODS: A single-institution
      retrospective study was conducted among all adult KTR with CDI, defined as a
      positive test for C. difficile by a cell cytotoxic assay for C. difficile toxin A
      or B or polymerase chain reaction test for toxigenic C. difficile. RESULTS: Among
      603 kidney transplants performed between 1 January 2008 and 31 December 2010, 37
      (6.1%) patients developed CDI: 12 (of 128; 9.4%) high-risk (blood group
      incompatible and/or anti-human leukocyte antigen donor-specific antibodies) vs.
      25 (of 475; 5.3%, P = 0.08) standard-risk patients. The overall rate of CDI
      increased from 3.7% in 2008 to 9.4% in 2010 (P = 0.05). The median time to CDI
      diagnosis was 9 days, with 27 (73.0%) patients developing CDI within the first 30
      days after their transplant, and 14 (51.8%) developing CDI within 7 days. A case
      control analysis of 37 CDI cases and 74 matched controls demonstrated the
      following predictors for CDI among KTR: vancomycin-resistant Enterococcus
      colonization before transplant (odds ratio [OR]: 3.6, P = 0.03), receipt of an
      organ from Centers for Disease Control high-risk donor (OR: 5.9, P = 0.006), and
      administration of high-risk antibiotics within 30 days post transplant (OR: 6.6,
      P = 0.001). CONCLUSIONS: CDI remains a common early complication in KTR, with
      rates steadily increasing during the study period. Host and transplant-related
      factors and exposure to antibiotics appeared to significantly impact the risk for
      CDI among KTR.

PMID- 23173774
TI  - Prevention of anxiety disorders in primary care: a feasibility study.
AB  - BACKGROUND: Anxiety disorders are highly prevalent in primary care and cause a
      substantial burden of disease. Screening on risk status, followed by preventive
      interventions in those at risk may prevent the onset of anxiety disorders, and
      thereby reduce the disease burden. The willingness to participate in screening
      and interventions is crucial for the scope of preventive strategies, but unknown.
      This feasibility study, therefore, investigated participation rates of screening
      and preventive services for anxiety disorders in primary care, and explored
      reasons to refrain from screening. METHODS: In three general practices, screening
      was offered to individuals visiting their general practitioner (total n = 2454).
      To assess risk status, a 10-item questionnaire was followed by a telephone
      interview (including the CIDI) when scoring above a predefined threshold.
      Preventive services were offered to those at risk. Participation rates for
      screening and preventive services for anxiety disorders were assessed. Those not
      willing to be screened were asked for their main reason to refrain from
      screening. RESULTS: Of all individuals, 17.3% participated in initial screening,
      and of those with a possible risk status, 56.0% continued screening. In 30.1% of
      those assessed, a risk status to develop an anxiety disorder was verified. Of
      these, 22.6% already received some form of mental health treatment and 38.7% of
      them agreed to participate in a preventive intervention and were referred. The
      most frequently mentioned reasons to refrain from screening were the emotional
      burden associated with elevated risk status, the assumption not to be at risk,
      and a lack of motivation to act upon an elevated risk status by using preventive
      services. CONCLUSIONS: Screening in general practice, followed by offering
      services to prevent anxiety disorders in those at risk did not appear to be a
      feasible strategy due to low participation rates. To enable the development of
      feasible and cost-effective preventive strategies, exploring the reasons of low
      participation rates, considering involving general practitioners in preventive
      strategies, and looking at preventive strategies in somatic health care with
      proven feasibility may be helpful.

PMID- 23173775
TI  - A nu-support vector regression based approach for predicting imputation quality.
AB  - BACKGROUND: Decades of genome-wide association studies (GWAS) have accumulated
      large volumes of genomic data that can potentially be reused to increase
      statistical power of new studies, but different genotyping platforms with
      different marker sets have been used as biotechnology has evolved, preventing
      pooling and comparability of old and new data. For example, to pool together data
      collected by 550K chips with newer data collected by 900K chips, we will need to
      impute missing loci. Many imputation algorithms have been developed, but the
      posteriori probabilities estimated by those algorithms are not a reliable measure
      the quality of the imputation. Recently, many studies have used an imputation
      quality score (IQS) to measure the quality of imputation. The IQS requires to
      know true alleles to estimate. Only when the population and the imputation loci
      are identical can we reuse the estimated IQS when the true alleles are unknown.
      METHODS: Here, we present a regression model to estimate IQS that learns from
      imputation of loci with known alleles. We designed a small set of features, such
      as minor allele frequencies, distance to the nearest known cross-over hotspot,
      etc., for the prediction of IQS. We evaluated our regression models by estimating
      IQS of imputations by BEAGLE for a set of GWAS data from the NCBI GEO database
      collected from samples from different ethnic populations. RESULTS: We construct a
      nu-SVR based approach as our regression model. Our evaluation shows that this
      regression model can accomplish mean square errors of less than 0.02 and a
      correlation coefficient close to 0.75 in different imputation scenarios. We also
      show how the regression results can help remove false positives in association
      studies. CONCLUSION: Reliable estimation of IQS will facilitate integration and
      reuse of existing genomic data for meta-analysis and secondary analysis.
      Experiments show that it is possible to use a small number of features to regress
      the IQS by learning from different training examples of imputation and IQS pairs.

PMID- 23173776
TI  - Molecular diagnostic and predictive tests in the evolution of chronic hepatitis C
      anti-viral therapies.
AB  - Since the discovery of HCV, polymerase chain reaction (PCR) has significantly
      contributed to the understanding of the virus life cycle and its replicative
      kinetics during anti-viral therapy. Parallel to the progression of dual and
      triple combination treatment, real-time PCR molecular tests have constantly
      improved in their ability to monitor viral load and drive personalized management
      schedules. The current sensitivity, accuracy and dynamic range of the available
      assays fulfil the requirement of "companion diagnostics" and support the
      development of new directly acting antiviral (DAA)-based regimens.

PMID- 23173777
TI  - Morpho-functional gastric pre-and post-operative changes in elderly patients
      undergoing laparoscopic cholecystectomy for gallstone related disease.
AB  - BACKGROUND: Cholecystectomy, gold standard treatment for gallbladder lithiasis,
      is closely associated with increased bile reflux into the stomach as amply
      demonstrated by experimental studies. The high prevalence of gallstones in the
      population and the consequent widespread use of surgical removal of the
      gallbladder require an assessment of the relationship between cholecystectomy and
      gastric mucosal disorders.Morphological evaluations performed on serial pre and
      post - surgical biopsies have provided new acquisitions about gastric damage
      induced by bile in the organ. METHODS: 62 elderly patients with gallstone related
      disease were recruited in a 30 months period. All patients were subjected to the
      most appropriate treatment (Laparoscopic cholecystectomy). The subjects had a pre
      surgical evaluation with:* dyspeptic symptoms questionnaire,* gastric endoscopy
      with body, antrum, and fundus random biopsies,* histo-pathological analysis of
      samples and elaboration of bile reflux index (BRI).The same evaluation was
      repeated at a 6 months follow-up. RESULTS: In our series the duodeno-gastric
      reflux and the consensual biliary gastritis, assessed histologically with the
      BRI, was found in 58% of the patients after 6 months from cholecystectomy. The
      demonstrated bile reflux had no effect on H. pylori's gastric colonization nor on
      the induction of gastric precancerous lesions. CONCLUSIONS: Cholecystectomy, gold
      standard treatment for gallstone-related diseases, is practiced in a high
      percentage of patients with this condition. Such procedure, considered by many
      harmless, was, in our study, associated with a significant risk of developing
      biliary gastritis after 6 months during the postoperative period.

PMID- 23173778
TI  - Mammographic density and estimation of breast cancer risk in intermediate risk
      population.
AB  - It is not clear to what extent mammographic density represents a risk factor for
      breast cancer among women with moderate risk for disease. We conducted a
      population-based study to estimate the independent effect of breast density on
      breast cancer risk and to evaluate the potential of breast density as a marker of
      risk in an intermediate risk population. From November 2006 to April 2009, data
      that included American College of Radiology Breast Imaging Reporting and Data
      System (BI-RADS) breast density categories and risk information were collected on
      52,752 women aged 50-69 years without previously diagnosed breast cancer who
      underwent screening mammography examination. A total of 257 screen-detected
      breast cancers were identified. Logistic regression was used to assess the effect
      of breast density on breast carcinoma risk and to control for other risk factors.
      The risk increased with density and the odds ratio for breast cancer among women
      with dense breast (heterogeneously and extremely dense breast), was 1.9 (95%
      confidence interval, 1.3-2.8) compared with women with almost entirely fat
      breasts, after adjustment for age, body mass index, age at menarche, age at
      menopause, age at first childbirth, number of live births, use of oral
      contraceptive, family history of breast cancer, prior breast procedures, and
      hormone replacement therapy use that were all significantly related to breast
      density (p < 0.001). In multivariate model, breast cancer risk increased with
      age, body mass index, family history of breast cancer, prior breast procedure and
      breast density and decreased with number of live births. Our finding that
      mammographic density is an independent risk factor for breast cancer indicates
      the importance of breast density measurements for breast cancer risk assessment
      also in moderate risk populations.

PMID- 23173779
TI  - Nutritional and cognitive status of entry-level primary school children in Zomba,
      rural Malawi.
AB  - Entry-level Malawian children (n = 226) aged 6-8 years from two public primary
      schools, one a participant in a national school feeding programme (FP), the other
      not, were investigated for differences in nutritional and cognitive status.
      Stunted growth (42%) and underweight (25%) were prevalent, with no significant
      differences between the schools, although the school attended was a significant
      predictor of mid-upper arm circumference. Previous attendance at a community
      based childcare centre was significantly associated with lower body weight and
      height. There were no significant differences in memory, reversal learning and
      attention outcomes between the schools. These findings report no major
      significant difference in nutrition or cognitive statuses between the schools,
      and on this basis suggest that both schools were equally in need of FP
      participation. More inclusive interventions and broadening/review of FP
      participation criteria are recommended.

PMID- 23173780
TI  - Advanced glycation end products augment experimental hepatic fibrosis.
AB  - BACKGROUND AND AIMS: Advanced glycation end products (AGEs) are nonenzymatic
      modifications of proteins by reducing sugars. These compounds accumulate in a
      number of chronic disease states, contributing to tissue injury via several
      mechanisms, including activation of the receptor for advanced glycation end
      products (RAGE). We aimed to investigate whether AGEs can exacerbate chronic
      liver injury and contribute to hepatic fibrosis. METHODS: We initially studied
      the effects of chronic hepatic exposure to high levels of AGEs given
      intraperitoneally as AGE-rat serum albumin. In a separate experiment, we examined
      the impact of high AGE exposure in rats following bile duct ligation (BDL).
      RESULTS: In normal rats, chronic AGE-rat serum albumin administration induced
      significant increases in alpha-smooth muscle actin gene and protein expression
      but did not induce fibrosis or biochemical evidence of liver injury. However, in
      BDL animals, AGE-bovine serum albumin administration significantly increased
      hepatic fibrosis as evidenced by increased collagen content and alpha-smooth
      muscle actin expression, compared with BDL alone. Furthermore, AGEs increased
      hepatic oxidative stress and receptor for advanced glycation end products gene
      expression. CONCLUSIONS: These findings suggest that AGEs may contribute to the
      pathogenesis of chronic liver injury and fibrosis.

PMID- 23173781
TI  - Evidence for validity of five secondary data sources for enumerating retail food
      outlets in seven American Indian communities in North Carolina.
AB  - BACKGROUND: Most studies on the local food environment have used secondary
      sources to describe the food environment, such as government food registries or
      commercial listings (e.g., Reference USA). Most of the studies exploring evidence
      for validity of secondary retail food data have used on-site verification and
      have not conducted analysis by data source (e.g., sensitivity of Reference USA)
      or by food outlet type (e.g., sensitivity of Reference USA for convenience
      stores). Few studies have explored the food environment in American Indian
      communities. To advance the science on measuring the food environment, we
      conducted direct, on-site observations of a wide range of food outlets in
      multiple American Indian communities, without a list guiding the field
      observations, and then compared our findings to several types of secondary data.
      METHODS: Food outlets located within seven State Designated Tribal Statistical
      Areas in North Carolina (NC) were gathered from online Yellow Pages, Reference
      USA, Dun & Bradstreet, local health departments, and the NC Department of
      Agriculture and Consumer Services. All TIGER/Line 2009 roads (>1,500 miles) were
      driven in six of the more rural tribal areas and, for the largest tribe, all
      roads in two of its cities were driven. Sensitivity, positive predictive value,
      concordance, and kappa statistics were calculated to compare secondary data
      sources to primary data. RESULTS: 699 food outlets were identified during primary
      data collection. Match rate for primary data and secondary data differed by type
      of food outlet observed, with the highest match rates found for grocery stores
      (97%), general merchandise stores (96%), and restaurants (91%). Reference USA
      exhibited almost perfect sensitivity (0.89). Local health department data had
      substantial sensitivity (0.66) and was almost perfect when focusing only on
      restaurants (0.91). Positive predictive value was substantial for Reference USA
      (0.67) and moderate for local health department data (0.49). Evidence for
      validity was comparatively lower for Dun & Bradstreet, online Yellow Pages, and
      the NC Department of Agriculture. CONCLUSIONS: Secondary data sources both over-
      and under-represented the food environment; they were particularly problematic
      for identifying convenience stores and specialty markets. More attention is
      needed to improve the validity of existing data sources, especially for rural
      local food environments.

PMID- 23173784
TI  - Epidemiology and genetic characterization of equine infectious anaemia virus
      strains isolated in Belgium in 2010.
AB  - In January 2010, the United Kingdom notified cases of equine infectious anaemia
      (EIA) in two horses introduced from Belgium. The animals came from one assembly
      centre in Romania and had transited through Belgium with 16 other horses. Nine of
      them, bought by a Belgian horse breeder, were investigated in Belgium and
      revealed one additional EIA-positive animal. Afterwards, the Belgian Federal
      Agency for the Safety of the Food Chain (FASFC) organized a serological EIA
      survey of the horses introduced into Belgium from Romania between 2007 and 2009.
      Among the 95 horses identified, six additional serological positive cases were
      found that had been introduced into Belgium in 2008 (n = 4) and in 2009 (n = 2).
      The survey was extended to the horses in contact with the positive cases, but all
      contact animals were negative, indicating the absence of transmission.
      Virological examination performed on tissue samples collected from two
      seropositive animals demonstrated the presence of viral DNA of EIA virus.
      Phylogenetic analysis based on the sequences of EIA virus gag gene clustered the
      Belgian isolates with Romanian strains isolated in 2009. The presumption of a
      common Belgian origin could be rejected. 

PMID- 23173782
TI  - RACK1 identified as the PCBP1-interacting protein with a novel functional role on
      the regulation of human MOR gene expression.
AB  - Poly C binding protein 1 (PCBP1) is an expressional regulator of the mu-opioid
      receptor (MOR) gene. We hypothesized the existence of a PCBP1 co-regulator
      modifying human MOR gene expression by protein-protein interaction with PCBP1. A
      human brain cDNA library was screened using the two-hybrid system with PCBP1 as
      the bait. Receptor for activated protein kinase C (RACK1) protein, containing
      seven WD domains, was identified. PCBP1-RACK1 interaction was confirmed via in
      vivo validation using the two-hybrid system, and by co-immunoprecipitation with
      anti-PCBP1 antibody and human neuronal NMB cell lysate, endogenously expressing
      PCBP1 and RACK1. Further co-immunoprecipitation suggested that RACK1-PCBP1
      interaction occurred in cytosol alone. Single and serial WD domain deletion
      analyses demonstrated that WD7 of RACK1 is the key domain interacting with PCBP1.
      RACK1 over-expression resulted in a dose-dependent decrease of MOR promoter
      activity using p357 plasmid containing human MOR promoter and luciferase reporter
      gene. Knock-down analysis showed that RACK1 siRNA decreased the endogenous RACK1
      mRNA level in NMB, and elevated MOR mRNA level as indicated by RT-PCR. Likewise,
      a decrease of RACK1 resulted in an increase of MOR proteins, verified by (3) H
      diprenorphine binding assay. Collectively, this study reports a novel role of
      RACK1, physically interacting with PCBP1 and participating in the regulation of
      human MOR gene expression in neuronal NMB cells.

PMID- 23173785
TI  - Induction of cross-protection against influenza A virus by DNA prime-intranasal
      protein boost strategy based on nucleoprotein.
AB  - BACKGROUND: The highly conserved nucleoprotein (NP) is an internal protein of
      influenza virus and is capable of inducing cross-protective immunity against
      different influenza A viruses, making it a main target of universal influenza
      vaccine. In current study, we characterized the immune response induced by DNA
      prime-intranasal protein boost strategy based on NP (A/PR/8/34, H1N1) in mouse
      model, and evaluated its protection ability against a lethal dose challenge of
      influenza virus. RESULTS: The intranasal boost with recombinant NP (rNP) protein
      could effectively enhance the pre-immune response induced by the NP DNA vaccine
      in mice. Compared to the vaccination with NP DNA or rNP protein alone, the prime
      boost strategy increased the level of NP specific serum antibody, enhanced the T
      cell immune response, and relatively induced more mucosal IgA antibody. The
      overall immune response induced by this heterologous prime-boost regimen was Th-1
      biased. Furthermore, the immune response in mice induced by this strategy
      provided not only protection against the homologous virus but also cross
      protection against a heterosubtypic H9N2 strain. CONCLUSIONS: The NP DNA prime
      intranasal protein boost strategy may provide an effective strategy for universal
      influenza vaccine development.

PMID- 23173786
TI  - Copy number variations identified in the chicken using a 60K SNP BeadChip.
AB  - Copy number variation (CNV) is considered an important genetic variation,
      contributing to many economically important traits in the chicken. Although CNVs
      can be detected using a comparative genomic hybridization array, the high-density
      SNP array has provided an alternative way to identify CNVs in the chicken. In the
      current study, a chicken 60K SNP BeadChip was used to identify CNVs in two
      distinct chicken genetic lines (White Leghorn and dwarf) using the PENNCNV
      program. A total of 209 CNV regions were identified, distributing on chromosomes
      1-22 and 24-28 and encompassing 13.55 Mb (1.42%) of chicken autosomal genome
      area. Three of seven selected CNVs (73.2% individuals) were completely validated
      by quantitative PCR. To our knowledge, this is the first report in the chicken
      identifying CNVs using a SNP array. Identification of 190 new identified CNVs
      illustrates the feasibility of the chicken 60K SNP BeadChip to detect CNVs in the
      chicken, which lays a solid foundation for future analyses of associations of
      CNVs with economically important phenotypes in chickens.

PMID- 23173788
TI  - Tissue analysis - a powerful tool for drug discovery and development.

PMID- 23173787
TI  - Nutritional status of young children in Mumbai slums: a follow-up anthropometric
      study.
AB  - BACKGROUND: Chronic childhood malnutrition remains common in India. As part of an
      initiative to improve maternal and child health in urban slums, we collected
      anthropometric data from a sample of children followed up from birth. We
      described the proportions of underweight, stunting, and wasting in young
      children, and examined their relationships with age. METHODS: We used two linked
      datasets: one based on institutional birth weight records for 17 318 infants,
      collected prospectively, and one based on follow-up of a subsample of 1941
      children under five, collected in early 2010. RESULTS: Mean birth weight was 2736
      g (SD 530 g), with a low birth weight (<2500 g) proportion of 22%. 21% of infants
      had low weight for age standard deviation (z) scores at birth (<-2 SD). At follow
      up, 35% of young children had low weight for age, 17% low weight for height, and
      47% low height for age. Downward change in weight for age was greater in children
      who had been born with higher z scores. DISCUSSION: Our data support the idea
      that much of growth faltering was explained by faltering in height for age,
      rather than by wasting. Stunting appeared to be established early and the
      subsequent decline in height for age was limited. Our findings suggest a focus on
      a younger age-group than the children over the age of three who are prioritized
      by existing support systems. FUNDING: The trial during which the birth weight
      data were collected was funded by the ICICI Foundation for Inclusive Growth
      (Centre for Child Health and Nutrition), and The Wellcome Trust (081052/Z/06/Z).
      Subsequent collection, analysis and development of the manuscript was funded by a
      Wellcome Trust Strategic Award: Population Science of Maternal and Child Survival
      (085417ma/Z/08/Z). D Osrin is funded by The Wellcome Trust (091561/Z/10/Z).

PMID- 23173789
TI  - MALDI imaging MS analysis of drug distribution in tissue: the right time!(?).

PMID- 23173791
TI  - Conference report: emerging technology for bioanalysis in the next decade.
AB  - This University of Wisconsin School of Pharmacy bioanalytical conference is
      presented each year by the Extension Services in Pharmacy, the professional
      development department within the School. The purpose of this 4-day conference is
      to provide an educational forum to discuss issues and applications associated
      with the analysis of xenobiotics, metabolites, biologics and biomarkers in
      biological matrices. The conference is designed to include and encourage an open
      exchange of scientific and methodological applications for bioanalysis. To
      increase the interactive nature of the conference, the program was a mixture of
      lectures, poster sessions, round table discussions and workshops. This article
      summarizes the presentations at the 13th Annual Conference.

PMID- 23173792
TI  - Quantitative determination of erlotinib and O-desmethyl erlotinib in human EDTA
      plasma and lung tumor tissue.
AB  - BACKGROUND: To increase knowledge about lung tumor tissue levels of erlotinib and
      its primary active metabolite, and about erlotinib plasma levels in intercalated
      dosing schedules, a sensitive and accurate method for determination of erlotinib
      and O-desmethyl erlotinib (OSI-420) in human plasma and lung tumor tissue has
      been developed. RESULTS: A method with HPLC-MS/MS was validated over a linear
      range from 5 to 2500 ng/ml in plasma and from 5.0 to 500 ng/ml for lung tumor
      tissue homogenate (50-5000 ng/g for lung tumor). Calibration curves in plasma
      were used to quantify analytes in lung tumor tissue homogenate. Lung tumor tissue
      of 15 patients has been collected and analyzed with the presented method.
      CONCLUSION: This method has been successfully validated and applied to determine
      plasma and lung tumor tissue concentrations of erlotinib and O-desmethyl
      erlotinib in patients with non-small-cell lung cancer.

PMID- 23173793
TI  - Evaluation of surrogate matrices for standard curve preparation in tissue
      bioanalysis.
AB  - BACKGROUND: The aim of this work was to investigate the feasibility of using
      tissue surrogate matrices and plasma for determining drug concentrations in
      tissues by LC-MS/MS. RESULTS: The similarity of tissues was evaluated using eight
      model compounds with different SlogP values. For plasma dilution, the overall
      matrix effects of tissue samples were found to approximate to those of pure
      plasma samples when plasma percentage was increased. When a ten-fold plasma
      dilution was applied, the differences between the instrumental responses of
      diluted tissue samples and pure plasma samples with the same spiked
      concentrations were within +/-20%. The results of tissue bioanalysis using plasma
      dilution and plasma curve for in vivo studies were acceptable with an averaged
      deviation of +/-20-25% compared with data using traditional tissue curves.
      CONCLUSION: Results demonstrate that tissue samples can be quantified using
      surrogate matrices. Plasma standard curves can be used for quantitation of both
      plasma and plasma-diluted tissue samples.

PMID- 23173794
TI  - Tissue bioanalysis of biotherapeutics and drug targets to support PK/PD.
AB  - Contemporary drug discovery leverages quantitative modeling and simulation with
      increasing emphasis, both to gain deeper knowledge of drug targets and mechanisms
      as well as improve predictions between preclinical models and clinical
      applications, such as first-in-human dose projections. Proliferation of novel
      biotherapeutic modalities increases the need for applied PK/PD modeling as a
      quantitative tool to advance new therapies. Of particular relevance is the
      understanding of exposure, target binding and associated pharmacology at the
      target site of interest. Bioanalytical methods are key to informing PK/PD models
      and require assessment of both PK and PD end points. Where targets are
      sequestered in tissues (noncirculating), the ability to quantitatively measure
      drug or biomarker in tissue compartments becomes particularly important. This
      perspective provides an overview of contemporary applications of quantitative
      bioanalysis in tissue compartments as applied to PK and PD assessments associated
      with novel biotherapeutics. Case studies and key references are provided.

PMID- 23173795
TI  - In vivo solid-phase microextraction for tissue bioanalysis.
AB  - Conventional in vitro or ex vivo bioanalytical quantitative sample preparation
      methods for the determination of compounds in biological tissues are often
      coupled with challenges in obtaining an assay representative of the system of
      interest. The rising interest in in vivo microsampling bioanalytical methods is
      due to the unique advantages they offer over their in vitro counterparts. In vivo
      solid-phase microextraction (SPME), a diffusion-based microsampling tool, has
      been successfully applied in recent studies to various biological systems. This
      review presents recent trends in tissue bioanalysis using in vivo SPME as a
      sample preparation tool. Efforts were made to discuss the various bioapplications
      of the method while highlighting possible strategies for improved sensitivity
      where needed. In vivo SPME devices currently employed for the various
      applications have also been described. In addition, we highlight selectivity of a
      new class of biocompatible coatings that can potentially improve the coverage of
      metabolites for untargeted metabolomics.

PMID- 23173796
TI  - A primer for best practices in tissue preparation for bioanalysis.
AB  - Analysis of drugs, biomarkers and their metabolites in tissue samples has always
      been an important aspect of the drug-development process. In the last decade,
      significant improvements in equipment and processes have made handling such
      samples far more efficient, with higher precision, accuracy and ruggedness. The
      purpose of this paper is to provide a primer for best practices of tissue
      analysis, including brief but specific tutorials on basic principles and
      laboratory operation. Included will be a discussion of what to consider when
      designing a study, tools available to make appropriate pre-study decisions,
      approaches for tissue acquisition and extraction, sample processing methods, and
      tips on creation of standards and QCs. We will offer some practical advice to
      help scientists who have good analytical skills, but are not experienced in
      tissue analysis to quickly start their own analyses with the minimum amount of
      time, labor and cost.

PMID- 23173797
TI  - Bioanalysis of drug in tissue: current status and challenges.
AB  - Distribution of drugs into tissues is an important determinant of the overall PK
      and PD profile. Thus, bioanalysis of drugs and their metabolites in tissues can
      play an important role in understanding the pharmacological and toxicological
      properties of new drug candidates. Unlike liquid matrices, bioanalysis in tissues
      offers unique challenges such as proper tissue sampling, appropriate tissue
      sample preparation, efficient extraction of the analytes from the tissue
      homogenates, and demonstration of stability and recovery of analytes in intact
      tissues. This article provides a systematic review of tissue sample analysis for
      small molecules using LC-MS/MS. The authors provide rationale for tissue sample
      analysis, and discuss strategies for method development, method qualification or
      validation, and sample analysis. Unique aspects of method development and
      qualification/validation are highlighted based on authors' direct experiences and
      literature summary. Analysis using intact tissue samples such as MALDI imaging is
      also briefly discussed.

PMID- 23173799
TI  - Defective ATM-Kap-1-mediated chromatin remodeling impairs DNA repair and
      accelerates senescence in progeria mouse model.
AB  - ATM-mediated phosphorylation of KAP-1 triggers chromatin remodeling and
      facilitates the loading and retention of repair proteins at DNA lesions. Mouse
      embryonic fibroblasts (MEFs) derived from Zmpste24(-/-) mice undergo early
      senescence, attributable to delayed recruitment of DNA repair proteins. Here, we
      show that ATM-Kap-1 signaling is compromised in Zmpste24(-/-) MEFs, leading to
      defective DNA damage-induced chromatin remodeling. Knocking down Kap-1 rescues
      impaired chromatin remodeling, defective DNA repair and early senescence in
      Zmpste24(-/-) MEFs. Thus, ATM-Kap-1-mediated chromatin remodeling plays a
      critical role in premature aging, carrying significant implications for progeria
      therapy.

PMID- 23173801
TI  - Instrumental lying by parents in the US and China.
AB  - The practice of lying to one's children to encourage behavioral compliance was
      investigated among parents in the US (N = 114) and China (N = 85). The vast
      majority of parents (84% in the US and 98% in China) reported having lied to
      their children for this purpose. Within each country, the practice most
      frequently took the form of falsely threatening to leave a child alone in public
      if he or she refused to follow the parent. Crosscultural differences were seen: A
      larger proportion of the parents in China reported that they employed
      instrumental lie-telling to promote behavioral compliance, and a larger
      proportion approved of this practice, as compared to the parents in the US. This
      difference was not seen on measures relating to the practice of lying to promote
      positive feelings, or on measures relating to statements about fantasy characters
      such as the tooth fairy. Findings are discussed with reference to sociocultural
      values and certain parenting-related challenges that extend across cultures.

PMID- 23173800
TI  - The role of atherectomy in the treatment of lower extremity peripheral artery
      disease.
AB  - BACKGROUND: The incidence of lower extremity peripheral artery disease (LE-PAD)
      continues to increase and associated morbidity remains high. Despite the
      significant development of percutaneous revascularization strategies, over the
      past decade, LE-PAD still represents a unique challenge for interventional
      cardiologists and vascular surgeons. METHOD: Typical features of atherosclerosis
      that affects peripheral vascular bed (diffuse nature, poor distal runoff,
      critical limb ischemia, chronic total occlusion) contribute to the disappointing
      results of traditional percutaneous transluminal angioplasty (PTA). New
      technologies have been developed in attempt to improve the safety and
      effectiveness of percutaneous revascularization. Among these, atherectomy,
      debulking and removing atherosclerotic plaque, offers the potential advantage of
      eliminating stretch on arterial walls and reducing rates of restenosis.
      CONCLUSIONS: This review summarizes the features and the current applications of
      new debulking devices.

PMID- 23173803
TI  - The NHS Cervical Screening Programme criteria for evaluating cervical cytology:
      comparison of the new with the old.

PMID- 23173804
TI  - ABC3 Part I: a review of the guidelines for terminology, classification and
      management of cervical cytology in England.
AB  - The provision of guidance on cytology reporting and evaluation, first outlined in
      1995 with the publication of Achievable Standards, Benchmarks for Reporting, and
      Criteria for Evaluating Cervical Cytopathology (ABC), and subsequently revised
      and expanded in a second edition in 2000, has been pivotal to the success of the
      National Health Service Cervical Screening Programme (NHSCSP), ensuring that
      standards are upheld, and that rigorous evaluation and quality assurance take
      place. In the last decade, major changes to the NHSCSP, notably the adoption of
      revised age ranges and screening intervals for all women in England,
      implementation of liquid-based cytology and, most recently, the decision to
      introduce high-risk human papillomavirus (HR-HPV) testing for triage of low-grade
      and borderline (equivalent to 'atypical') cytological abnormalities and test of
      cure after treatment of cervical intraepithelial neoplasia (CIN) determined that
      an updated version of ABC was required. The third edition of ABC recommends
      adoption, with minor modification, of the revised British Society for Clinical
      Cytology terminology and provides guidance on the management of abnormal cytology
      results linked to this terminology taking account of HR-HPV testing. To
      accommodate these changes, expanded result codes, which are electronic codes used
      to transfer management information to central computers for follow-up, call and
      recall of individual women, have been developed. Further guidance on specimen
      adequacy is also provided. Revised performance indicators are described and
      explained in a separate article by R. Blanks in this issue of Cytopathology. All
      the changes in ABC3 are designed to support the mission statement of the NHSCSP
      that 'the objective of cervical screening is to reduce cervical cancer incidence
      and mortality by screening with a high sensitivity for the detection of CIN2 or
      worse, whilst maintaining a high specificity'.

PMID- 23173805
TI  - ABC3 Part II: a review of the new criteria for evaluating cervical cytology in
      England.
AB  - The new Achievable Standards, Benchmarks for Reporting, and Criteria for
      Evaluating Cervical Cytopathology, 3rd edn (ABC3) includes radical changes in the
      criteria for evaluating cervical cytology. First, they include a new mission
      statement 'the objective of cervical screening is to reduce cervical cancer
      incidence and mortality by screening with a high sensitivity for the detection of
      CIN2 or worse, whilst maintaining a high specificity'. Second, the original four
      performance measurement criteria where laboratories were examined further if they
      were below the 10th or above the 90th percentile has been changed to three and
      laboratories are only mandatorily examined if they fall below the 5th or above
      the 95th percentile. The old criteria related to the percentage of samples that
      were inadequate, the percentage of all adequate samples reported as moderate
      dyskaryosis or worse (equivalent to high-grade squamous intraepithelial lesion or
      cancer), the percentage of adequate samples reported as mild dyskaryosis or
      borderline (equivalent to low-grade squamous intraepithelial lesion or atypical
      squamous/glandular cells) and the positive predictive value. The new criteria are
      percentage of inadequate samples, positive predictive value and a new measure
      termed referral value. These changes mean that far fewer laboratories will
      require mandatory examination. Third, a raft of optional performance measures
      have been introduced to help laboratories examine their annual statistical return
      to the Department of Health in comparison with other laboratories. These measures
      have been designed to produce a more uniform national programme, and to help
      laboratories decide whether they are maximizing the benefit of screening while
      minimizing the harm, which is the goal of all screening programmes. This review
      examines in detail the new criteria and explains in more detail some of the
      thinking behind them.

PMID- 23173806
TI  - miR-210: a therapeutic target in cancer.
AB  - INTRODUCTION: As the predominant miRNA regulated by hypoxia, miR-210 correlates
      with survival in cancer patients. miR-210 may play important roles in regulation
      of cell growth, angiogenesis and apoptosis in different human tumor models,
      indicating that it can be used as a therapeutic target. AREAS COVERED: This
      review covers all literature related to miR-210 in malignant tumors from the past
      5 years, and analyzes the biological functions and molecular mechanisms of it.
      The authors also envisage future developments toward the clinical applications of
      miR-210 to cancer diagnosis and treatment. EXPERT OPINION: miR-210 may function
      as a new therapeutic target for anticancer intervention. Considering that the
      exact function of miR-210 is still not well characterized and understood, more
      investigations should be performed to promote the success of therapeutic-clinical
      use of miR-210 in cancer.

PMID- 23173807
TI  - Sutureless jejuno-jejunal anastomosis in gastric cancer patients: a comparison
      with handsewn procedure in a single institute.
AB  - BACKGROUND: The biofragmentable anastomotic ring has been used to this day for
      various types of anastomosis in the gastrointestinal tract, but it has not yet
      achieved widespread acceptance among surgeons. The purpose of this retrospective
      study is to compare surgical outcomes of sutureless with suture method of Roux
      and-Y jejunojejunostomy in patients with gastric cancer. METHODS: Two groups of
      patients were obtained based on anastomosis technique (sutureless group versus
      hand sewn group): perioperative outcomes were recorded for every patient.
      RESULTS: The mean time spent to complete a sutureless anastomosis was 11 +/- 4
      min, whereas the time spent to perform hand sewn anastomosis was 23 +/- 7 min.
      Estimated intraoperative blood loss was 178 +/- 32 ml in the sutureless group and
      182 +/- 23 ml in the suture-method group with no significant differences. No
      complications were registered related to enteroanastomosis. Intraoperative
      mortality was none for both groups. CONCLUSIONS: The Biofragmentable Anastomotic
      Ring offers a safe and time-saving method for the jejuno-jejunal anastomosis in
      gastric cancer surgery, and for this purpose the ring has been approved as a
      standard method in our clinic. Nevertheless currently there are few studies on
      upper gastrointestinal sutureless anastomoses and this could be the reason for
      the low uptake of this device.

PMID- 23173808
TI  - Delivery at 37 weeks' gestation is associated with a higher risk for child
      behavioural problems.
AB  - BACKGROUND: Advances in obstetric care have been accompanied by increasing rates
      of intervention which often involve elective delivery at 37 weeks, soon after
      term gestation has been achieved. AIM: The aim of this study was to examine the
      behavioural sequelae for children born at this early term gestational age
      compared with those born at later weeks. METHODS: The Western Australian
      Pregnancy Cohort (Raine) Study provided comprehensive obstetric data from 2900
      pregnancies. Offspring were followed up at ages two, five, eight, 10, 14 and 17
      years using the parent report Child Behaviour Checklist (CBCL) with clinical
      cutoffs for overall, internalising (withdrawn, somatic complaints,
      anxious/depressed) and externalising (delinquent, aggressive) behaviour (T-score
      >= 60). We used longitudinal logistic regression models incorporating generalised
      estimating equations (GEE) with step-wise adjustment for ante-, peri- and
      postnatal confounding factors. RESULTS: Approximately 9% of our cohort was born
      within the range of 37(0/7) and 37(6/7)  weeks. Those born at 37 weeks' gestation
      were at increased risk for overall (OR = 1.43, 95% CI = 1.02, 2.01) and
      externalising (OR = 1.42, 95% CI = 1.01, 2.01) behavioural problems in the fully
      adjusted model when compared with infants born from 39 weeks onwards. Infants
      born late preterm (34-36 weeks) and at 38 weeks did not show a significantly
      increased risk for behavioural problems. CONCLUSION: Infants born at 37 weeks'
      gestation are at increased risk for behavioural problems over childhood and
      adolescence compared with those born later in gestation. We suggest that 37
      weeks' gestation may not be the optimal cutoff for defining perinatal risk as it
      applies to behavioural development.

PMID- 23173809
TI  - The implications of biomarker evidence for systematic reviews.
AB  - BACKGROUND: In Evidence-Based Medicine, clinical practice guidelines and
      systematic reviews are crucial devices for medical practitioners in making
      clinical decision. Clinical practice guidelines are systematically developed
      statements to support health care decisions for specific circumstances whereas
      systematic reviews are summaries of evidence on clearly formulated clinical
      questions. Biomarkers are biological measurements (primarily molecular) that are
      used to diagnose, predict treatment outcomes and prognosticate disease and are
      increasingly used in randomized controlled trials (RCT). METHODS: We search
      PubMed for systematic reviews, RCTs, case reports and non-systematic reviews with
      and without mentions of biomarkers between years 1990-2011. We compared the
      frequency and growth rate of biomarkers and non-biomarkers publications. We also
      compared the growth of the proportion of biomarker-based RCTs with the growth of
      the proportion of biomarker-based systematic reviews. RESULTS: With 147,774
      systematic reviews indexed in PubMed from 1990 to 2011 (accessed on 18/10/2012),
      only 4,431 (3%) are dedicated to biomarkers. The annual growth rate of biomarkers
      publications is consistently higher than non-biomarkers publications, showing the
      growth in biomarkers research. From 20 years of systematic review publications
      indexed in PubMed, we identified a bias in systematic reviews against the
      inclusion of biomarker-based RCTs. CONCLUSIONS: With the realisation of genome
      based personalised medicine, biomarkers are becoming important for clinical
      decision making. The bias against the inclusion of biomarkers in systematic
      reviews leads to medical practitioners deprive of important information they
      require to address clinical questions. Sparse or weak evidence and lack of
      genetic training for systematic reviewers may contribute to this trend.

PMID- 23173810
TI  - Human epithelial stem cells persist within tissue-engineered skin produced by the
      self-assembly approach.
AB  - To adequately and permanently restore organ function after grafting, human tissue
      engineered skin substitutes (TESs) must ultimately contain and preserve
      functional epithelial stem cells (SCs). It is therefore essential that a maximum
      of SCs be preserved during each in vitro step leading to the production of TESs
      such as the culture process and the elaboration of a skin cell bank by
      cryopreservation. To investigate the presence and functionality of epithelial SCs
      within the human TESs made by the self-assembly approach, slow-cycling cells were
      identified using 5'-bromo-2'-deoxyuridine (BrdU) in the three-dimensional
      construct. A subset of basal epithelial cells retained the BrdU label and was
      positive for the SC-associated marker keratin 19 within TESs after a chase of 21
      days in culture post-BrdU labeling. Moreover, keratinocytes harvested from TESs
      gave rise to SC-like colonies in secondary monolayer subcultures, indicating that
      SCs were preserved within TESs. To evaluate the effect of cryopreservation with
      dimethyl sulfoxide and storage in liquid nitrogen on SCs, human epithelial cells
      were extracted from skin samples, amplified in culture, and used to produce TESs,
      before cryopreservation as well as after thawing. We found that the proportion
      and the growth potential of epithelial SCs in monolayer culture and in TESs
      remained constant before and after cryopreservation. Further, the functionality
      of these substitutes was demonstrated by successfully grafting human TESs on
      athymic mice for 6 months. We conclude that human epithelial skin SCs are
      adequately preserved upon human tissue reconstruction. Thus, these TESs produced
      by the self-assembly approach are suitable for clinical applications.

PMID- 23173811
TI  - Solution-processable ambipolar diketopyrrolopyrrole-selenophene polymer with
      unprecedentedly high hole and electron mobilities.
AB  - There is a fast-growing demand for polymer-based ambipolar thin-film transistors
      (TFTs), in which both n-type and p-type transistor operations are realized in a
      single layer, while maintaining simplicity in processing. Research progress
      toward this end is essentially fueled by molecular engineering of the conjugated
      backbones of the polymers and the development of process architectures for device
      fabrication, which has recently led to hole and electron mobilities of more than
      1.0 cm(2) V(-1) s(-1). However, ambipolar polymers with even higher performance
      are still required. By taking into account both the conjugated backbone and side
      chains of the polymer component, we have developed a dithienyl
      diketopyrrolopyrrole (TDPP) and selenophene containing polymer with hybrid
      siloxane-solubilizing groups (PTDPPSe-Si). A synergistic combination of rational
      polymer backbone design, side-chain dynamics, and solution processing affords an
      enormous boost in ambipolar TFT performance, resulting in unprecedentedly high
      hole and electron mobilities of 3.97 and 2.20 cm(2) V(-1) s(-1), respectively.

PMID- 23173812
TI  - Future research and collaboration: the "SINERGIE" project on HCV (South Italian
      Network for Rational Guidelines and International Epidemiology).
AB  - The SINERGIE (South Italian Network for Rational Guidelines and International
      Epidemiology) project is intended to set up a collaborative network comprising
      virologists, clinicians and public health officials dealing with patients
      affected by HCV disease in the Calabria Region. A prospective observational data
      base of HCV infection will be developed and used for studies on HCV natural
      history, response to treatment, pharmaco-economics, disease complications, and
      HCV epidemiology (including phylogenetic analysis). With this approach, we aim at
      improving the identification and care of patients, focusing on upcoming research
      questions. The final objective is to assist in improving care delivery and inform
      Public Health Authorities on how to optimize resource allocation in this area.

PMID- 23173813
TI  - Exogenously applied abscisic acid to Yan73 (V. vinifera) grapes enhances phenolic
      content and antioxidant capacity of its wine.
AB  - Yan73 is a 'teinturier' red wine variety cultivated in China and widely used in
      winemaking to strengthen red wine colour. The objective of this study was to
      evaluate the effect of exogenous abscisic acid (ABA) applied to the grapevine
      cluster on the antioxidant capacity and phenolic content of the wine made from
      Yan73. Two hundred mg/l ABA was applied on Yan73 grapevine cluster during
      veraison. As they mature, these ABA-treated and untreated grape berries were
      transformed into wines, respectively, and the phenolic content and antioxidant
      capacity of these wines were compared. The results showed that phenolic content
      (total phenolics, tannins, flavonoids and anthocyanins) and antioxidant capacity
      were higher in the wine produced with ABA-treated Yan73 grapes than those in the
      wine from untreated grapes. Compared to Cabernet Sauvignon wine, Yan73 wine had
      higher phenolic content and stronger antioxidant capacity. These strongly suggest
      that exogenously applied ABA to Yan73 grapes can enhance phenolic content and
      antioxidant capacity of its wine, and Yan73 wine has the higher utilization value
      and potential for development.

PMID- 23173814
TI  - Safety and efficacy of subretinal visual implants in humans: methodological
      aspects.
AB  - BACKGROUND: Replacing the function of visual pathway neurons by electronic
      implants is a novel approach presently explored by various groups in basic
      research and clinical trials. The novelty raises unexplored methodological
      aspects of clinical trial design that may require adaptation and validation.
      METHODS: We present procedures of efficacy and safety testing for subretinal
      visual implants in humans, as developed during our pilot trial 2005 to 2009 and
      multi-centre clinical trial since 2010. RESULTS: Planning such a trial requires
      appropriate inclusion and exclusion criteria. For subretinal electronic visual
      implants, patients with photoreceptor degeneration are the target patient group,
      whereas presence of additional diseases affecting clear optic media or the visual
      pathway must be excluded. Because sham surgery is not possible, a masked study
      design with implant power ON versus OFF is necessary. Prior to the efficacy
      testing by psychophysical tests, the implant's technical characteristics have to
      be controlled via electroretinography (ERG). Moreover the testing methods require
      adaptation to the particular technology. We recommend standardised tasks first to
      determine the light perception thresholds, light localisation and movement
      detection, followed by grating acuity and vision acuity test via Landolt C rings.
      A laboratory setup for assessing essential activities of daily living is
      presented. Subjective visual experiences with the implant in a natural
      environment, as well as questionnaires and psychological counselling are further
      important aspects. CONCLUSIONS: A clinical trial protocol for artificial vision
      in humans, which leads a patient from blindness to the state of very low vision
      is a challenge and cannot be defined completely prior to the study. Available
      tests of visual function may not be sufficiently suited for efficacy testing of
      artificial vision devices. A protocol based on experience with subretinal visual
      implants in 22 patients is presented that has been found adequate to monitor
      safety and efficacy.

PMID- 23173815
TI  - Where are the NGOs and why? The distribution of health and development NGOs in
      Bolivia.
AB  - BACKGROUND: The presence and influence of nongovernmental organizations (NGOs) in
      the landscape of global health and development have dramatically increased over
      the past several decades. The distribution of NGO activity and the ways in which
      contextual factors influence the distribution of NGO activity across geographies
      merit study. This paper explores the distribution of NGO activity, using Bolivia
      as a case study, and identifies local factors that are related to the
      distribution of NGO activity across municipalities in Bolivia. METHODS: The
      research question is addressed using a geographic information system (GIS) and
      multiple regression analyses of count data. We used count data of the total
      number of NGO projects across Bolivian municipalities to measure NGO activity
      both in general and in the health sector specifically and national census data
      for explanatory variables of interest. RESULTS: This study provides one of the
      first empirical analyses exploring factors related to the distribution of NGO
      activity at the national scale. Our analyses show that NGO activity in Bolivia,
      both in general and health-sector specific, is distributed unevenly across the
      country. Results indicate that NGO activity is related to population size, extent
      of urbanization, size of the indigenous population, and health system coverage.
      Results for NGO activity in general and health-sector specific NGO activity were
      similar. CONCLUSIONS: The uneven distribution of NGO activity may suggest a lack
      of co-ordination among NGOs working in Bolivia as well as a lack of co-ordination
      among NGO funders. Co-ordination of NGO activity is most needed in regions
      characterized by high NGO activity in order to avoid duplication of services and
      programmes and inefficient use of limited resources. Our findings also indicate
      that neither general nor health specific NGO activity is related to population
      need, when defined as population health status or education level or poverty
      levels. Considering these results we discuss broader implications for global
      health and development and make several recommendations relevant for development
      and health practice and research.

PMID- 23173816
TI  - Electrochemotherapy of cutaneous metastastes from breast cancer in elderly
      patients: a preliminary report.
AB  - BACKGROUND: The management of cutaneous metastases often represents a challenge
      because they may be widespread and may recur after radiotherapy or chemotherapy;
      breast cancer accounts for 51% of the total cases of cutaneous metastases. When
      surgical excision of chest wall recurrences is not possible and other local
      treatments such as radiotherapy or radiotherapy with hyperthermia fail, topical
      chemotherapy and electrochemotherapy (ECT) might be taken into account.ECT is a
      new local treatment of solid tumors which can be defined as the local
      potentiation, by means of permeabilizing electric pulses, of the antitumor
      activity of a non permeating anticancer drug with high intrinsic cytotoxicity.
      METHODS: This prospective observational study took place throughout March 2010 to
      October 2011. Twelve consecutive elderly patients (1 man and 11 women, median age
      of 76 years) with regional or distant skin or subcutaneous metastases from breast
      cancer, with or without visceral disease, were included in the study. Patient
      enrollment was carried out according to the ESOPE criteria. Bleomycin
      administration was followed by the application of brief electric pulses to each
      tumor nodule within 8 min after intravenous infusion of the drug. Electric
      currents were delivered by means of a 2-3 cm long needle electrode according to
      lesion size. All treatments were performed using the CliniporatorTM device.
      RESULTS: We observed Complete Response(CR) in 75.3% (107 metastases), Partial
      Response(PR) in 17% (24 metastases), no change in 7.7% (11 metastases) . No
      serious ECT-related adverse events were reported; adverse events consisted of
      pain in the treated area one to two days after treatment (1 patient, 8.3%) and
      ulceration of treated area (1 patient, 8.3%). CONCLUSION: ECT could be suggested
      as a primary local therapy in patients not suitable for surgical removal of the
      primary tumor, and clinicians should not hesitate to use it even in the elderly.

PMID- 23173817
TI  - Effect of age on the pharmacokinetics of a single daily dose of gentamicin
      sulfate in healthy foals.
AB  - REASONS FOR PERFORMING STUDY: Therapeutic drug monitoring in a small number of
      foals of various ages indicates that the standard adult dose of 6.6 mg/kg bwt q.
      24 h for gentamicin is too low and a dose of 12 mg/kg bwt has been proposed. The
      pharmacokinetics of this dosage in foals and the ages at which this higher dose
      should be used have not previously been investigated. OBJECTIVE: To determine the
      effect of age on the pharmacokinetics of a single 12 mg/kg bwt i.v. dose of
      gentamicin in foals. METHODS: Six healthy foals were given a single i.v. dose of
      gentamicin at 1-3 days, 2, 4, 8 and 12 weeks of age. Plasma concentrations were
      measured using LC-MS/MS. RESULTS: Elimination half-life (mean +/- s.d.) was
      significantly longer in 1-3-day-old foals (8.2 +/- 2.0 h) than in foals 4 weeks
      of age (3.7 +/- 1.5 h) or older. Volume of distribution was significantly higher
      in 1-3-day-old foals (0.75 +/- 0.20 l/kg bwt) than in 8- (0.27 +/- 0.10 l/kg bwt)
      or 12-week-old foals (0.29 +/- 0.11 l/kg bwt). Concentrations of gentamicin 1 h
      after administration were significantly lower in 1-3-day-old foals (20.52 +/-
      2.07 MUg/ml) than in all other age groups (>42.16 +/- 17.57 MUg/ml).
      Concentrations of gentamicin 24 h after administration were significantly higher
      in the 1-3-day-old foals (1.97 +/- 0.90 MUg/ml) than in all the other age groups
      (<0.85 +/- 0.46 MUg/ml). CONCLUSIONS: The pharmacokinetics of gentamicin change
      considerably in the first 2 weeks of life. POTENTIAL RELEVANCE: Intravenous
      administration of gentamicin at a dose of 12 mg/kg bwt q. 36 h would be required
      in foals less than 2 weeks of age. In foals 2 weeks of age or older, a lower dose
      of 6.6 mg/kg bwt given q. 24 h was predicted to be adequate.

PMID- 23173818
TI  - Statistical analysis of immuno-functionalized tumor-cell behaviors on
      nanopatterned substrates.
AB  - Laser scanning cytometry has been proven as a powerful technology for high
      content, high-throughput quantitative analysis of cellular functions in a fully
      automated manner. It utilizes a large-area fluorescence imaging scheme and
      rigorous image quantitation algorithms to enable informative analysis of cell
      samples attached to solid substrates. While this technology represents a powerful
      approach for high-content screening using cell lines, it has not been applied to
      the study of tumor-cell behaviors on these solid nanopatterned substrates after
      several hours of incubation. Herein, we statistically demonstrated functional
      cellular morphology information, including size, shape, and distribution of the
      captured cells after 0.5 to 45 h of incubation on nanopatterned substrates, such
      as silicon nanowires and quartz nanopillars, along with planar glass substrates.
      With increasing incubation time up to 45 h, we observed that the nanopatterned
      substrates could have not only increased adhesion and traction forces between
      cells and nanopatterned substrates, but also limited cell spreading on the
      substrates compared to the planar glass substrates. On the basis of our results,
      we suggest that the most important factors to influence the cell behaviors on the
      three solid substrates are the degree of dimension on cell behaviors and cell
      traction force.

PMID- 23173819
TI  - TIGRESS: Trustful Inference of Gene REgulation using Stability Selection.
AB  - BACKGROUND: Inferring the structure of gene regulatory networks (GRN) from a
      collection of gene expression data has many potential applications, from the
      elucidation of complex biological processes to the identification of potential
      drug targets. It is however a notoriously difficult problem, for which the many
      existing methods reach limited accuracy. RESULTS: In this paper, we formulate GRN
      inference as a sparse regression problem and investigate the performance of a
      popular feature selection method, least angle regression (LARS) combined with
      stability selection, for that purpose. We introduce a novel, robust and accurate
      scoring technique for stability selection, which improves the performance of
      feature selection with LARS. The resulting method, which we call TIGRESS (for
      Trustful Inference of Gene REgulation with Stability Selection), was ranked among
      the top GRN inference methods in the DREAM5 gene network inference challenge. In
      particular, TIGRESS was evaluated to be the best linear regression-based method
      in the challenge. We investigate in depth the influence of the various parameters
      of the method, and show that a fine parameter tuning can lead to significant
      improvements and state-of-the-art performance for GRN inference, in both directed
      and undirected settings. CONCLUSIONS: TIGRESS reaches state-of-the-art
      performance on benchmark data, including both in silico and in vivo (E. coli and
      S. cerevisiae) networks. This study confirms the potential of feature selection
      techniques for GRN inference. Code and data are available on
      http://cbio.ensmp.fr/tigress. Moreover, TIGRESS can be run online through the
      GenePattern platform (GP-DREAM, http://dream.broadinstitute.org).

PMID- 23173820
TI  - Outbreak of Burkholderia cepacia bloodstream infections traced to the use of
      Ringer lactate solution as multiple-dose vial for catheter flushing, Phnom Penh,
      Cambodia.
AB  - The Burkholderia cepacia complex is a group of Gram-negative bacteria known as
      respiratory pathogens in cystic fibrosis patients, but also increasingly reported
      as a cause of healthcare associated infections. We describe an outbreak of B.
      cepacia bloodstream infections in a referral hospital in Phnom Penh, Cambodia.
      Over a 1.5-month period, blood cultures from eight adult patients grew B.
      cepacia. Bloodstream infection occurred after a median of 2.5 days of
      hospitalisation. Three patients died: 7, 10 and 17 days after blood cultures were
      sampled. As part of the outbreak investigation, patient files were reviewed and
      environmental sampling was performed. All patients had peripheral venous
      catheters that were flushed with Ringer lactate drawn from a 1 L bag, used as
      multiple-dose vial at the ward. Cultures of unopened Ringer lactate and
      disinfectants remained sterile but an in-use bag of Ringer lactate solution and
      the dispensing pin grew B. cepacia. The isolates from patients and flushing
      solution were identified as B. cepacia by recA gene sequence analysis, and random
      amplified polymorphic DNA typing confirmed clonal relatedness. The onset of the
      outbreak had coincided with the introduction of a dispensing pin with a screw fit
      that did not allow proper disinfection. Re-enforcement of aseptic procedures with
      sterile syringe and needle has ended the outbreak. Growth of B. cepacia should
      alert the possibility of healthcare associated infection also in tropical
      resource-limited settings. The use of multiple-dose vials should be avoided and
      newly introduced procedures should be assessed for infection control risks.

PMID- 23173821
TI  - One-year maintenance outcomes among patients with moderately-to-severely active
      ulcerative colitis who responded to induction therapy with adalimumab: subgroup
      analyses from ULTRA 2.
AB  - BACKGROUND: Patients with moderately-to-severely active ulcerative colitis (UC)
      are unlikely to continue anti-TNF therapy in the absence of early therapeutic
      response. AIM: To assess week 52 efficacy, safety and benefit/risk balance of
      adalimumab treatment in patients with moderately-to-severely active UC failing
      conventional therapy who achieved clinical response at week 8 in the 52-week
      ULTRA 2 trial. METHODS: Patients randomised to adalimumab (160/80 mg, week 0/2;
      40 mg, every other week thereafter) in ULTRA 2 who achieved clinical response at
      week 8 per partial Mayo score (Mayo score without endoscopy subscore) were
      assessed for week 52 clinical remission, clinical response, mucosal healing,
      steroid-free remission and steroid discontinuation rates, overall and by prior
      anti-TNF use. Benefit/risk balance for the overall ITT population (regardless of
      week 8 responder status) was assessed using 'net efficacy adjusted for risk'
      (NEAR) odds ratios. Safety was assessed using adverse event rates. RESULTS: Of
      248 adalimumab-treated patients, 123 (49.6%) achieved clinical response at week
      8. Of these, 30.9%, 49.6%, and 43.1% achieved clinical remission, clinical
      response, and mucosal healing, respectively, at week 52. Of the week 8 responders
      using corticosteroids at baseline (N = 90), 21.1% achieved steroid-free remission
      and 37.8% were steroid-free at week 52. NEAR odds ratios indicated a positive
      benefit/risk balance for achievement of week 8 and week 52 response or remission
      without serious adverse events or serious infections. No safety concerns were
      identified. CONCLUSIONS: Adalimumab treatment was associated with a positive
      benefit/risk balance in the overall population of patients with moderately-to
      severely active ulcerative colitis in ULTRA 2; early response was predictive of a
      positive outcome at 1 year (NCT00408629).

PMID- 23173822
TI  - Differential association of postsynaptic signaling protein complexes in striatum
      and hippocampus.
AB  - Distinct physiological stimuli are required for bidirectional synaptic plasticity
      in striatum and hippocampus, but differences in the underlying signaling
      mechanisms are poorly understood. We have begun to compare levels and
      interactions of key excitatory synaptic proteins in whole extracts and
      subcellular fractions isolated from micro-dissected striatum and hippocampus.
      Levels of multiple glutamate receptor subunits, calcium/calmodulin-dependent
      protein kinase II (CaMKII), a highly abundant serine/threonine kinase, and
      spinophilin, a F-actin and protein phosphatase 1 (PP1) binding protein, were
      significantly lower in striatal extracts, as well as in synaptic and/or
      extrasynaptic fractions, compared with similar hippocampal extracts/fractions.
      However, CaMKII interactions with spinophilin were more robust in striatum
      compared with hippocampus, and this enhanced association was restricted to the
      extrasynaptic fraction. NMDAR GluN2B subunits associate with both spinophilin and
      CaMKII, but spinophilin-GluN2B complexes were enriched in extrasynaptic fractions
      whereas CaMKII-GluN2B complexes were enriched in synaptic fractions. Notably, the
      association of GluN2B with both CaMKII and spinophilin was more robust in
      striatal extrasynaptic fractions compared with hippocampal extrasynaptic
      fractions. Selective differences in the assembly of synaptic and extrasynaptic
      signaling complexes may contribute to differential physiological regulation of
      excitatory transmission in striatum and hippocampus.

PMID- 23173824
TI  - A synthetic oligopeptide derived from enamel matrix derivative promotes the
      differentiation of human periodontal ligament stem cells into osteoblast-like
      cells with increased mineralization.
AB  - BACKGROUND: In a previous study, the authors obtained a synthetic peptide (SP)
      for useful periodontal tissue regeneration. Periodontal ligament stem cells
      (PDLSCs) have multiple potentiality to contribute to tissue regeneration. The aim
      of this experiment is to investigate the effect of SP on human PDLSCs. METHODS:
      Periodontal ligament cells were obtained from healthy adult human third molars
      and used to isolate single PDLSC-derived colonies. The mesenchymal stem cell
      nature of the PDLSCs was confirmed by immunohistochemical evaluation of STRO-1
      expression. Proliferation and osteoblastic differentiation were investigated by
      culturing PDLSCs in normal or osteogenic medium with and without SP (100 ng/mL).
      Osteoblast differentiation was assessed by measuring alkaline phosphatase (ALP)
      activity, osteocalcin production, mRNA expression of osteonectin, mineralization,
      and calcium deposition. RESULTS: Isolated PDLSCs were immunohistochemically
      positive for vimentin and STRO-1 and negative for cytokeratin. A greater number
      of calcified nodules were observed in osteogenic medium culture with SP than
      without. In the early and later stages of PDLSC culture with SP, osteonectin
      production and osteocalcin production were increased. SP in culture with
      osteogenic medium significantly enhanced proliferation of PDLSCs, as well as ALP
      activity, expression of osteonectin, osteocalcin production, formation of
      calcified nodules, and mineralization. CONCLUSIONS: SP enhances the formation of
      calcified nodules and osteocalcin production in the culture of PDLSCs into
      osteoblast-like cells and is a useful material for periodontal tissue
      regeneration.

PMID- 23173823
TI  - Blocking proinflammatory cytokine release modulates peripheral blood mononuclear
      cell response to Porphyromonas gingivalis.
AB  - BACKGROUND: Chronic periodontitis (CP) is an inflammatory disease in which
      cytokines play a major role in the progression of disease. Anti-inflammatory
      cytokines (interleukin 4 [IL-4] and IL-10) were reported to be absent or reduced
      in diseased periodontal tissues, suggesting an imbalance between the
      proinflammatory and anti-inflammatory mediators. This study tests the hypothesis
      that there is cellular crosstalk mediated by proinflammatory and anti
      inflammatory cytokines and that blocking proinflammatory cytokine (tumor necrosis
      factor-alpha [TNF-alpha] and IL-1) production will enhance anti-inflammatory
      cytokine (IL-4 and IL-10) production from peripheral blood mononuclear cells
      (PBMCs) in response to Porphyromonas gingivalis. METHODS: PBMCs were isolated
      from individuals diagnosed with CP or healthy individuals and cultured for 24
      hours. Concanavalin A (ConA) was used as an activator of lymphocyte function.
      Live and heat-killed P. gingivalis or lipopolysaccharide from P. gingivalis were
      used as the bacterial stimulants. TNF-alpha and IL-1 production was neutralized
      by specific antibodies against TNF-alpha and IL-1alpha or IL-beta. Culture
      supernatants were evaluated by enzyme-linked immunosorbent assay for TNF-alpha,
      IL-1beta, IL-4, and IL-10 production. RESULTS: Live P. gingivalis did not result
      in any significant IL-10 or IL-4 release, whereas heat-killed P. gingivalis led
      to a significant increase in IL-10 levels compared with unstimulated or live P.
      gingivalis-stimulated cells from both healthy individuals or those with CP.
      Overall, PBMCs from patients with CP produced significantly lower IL-10 in
      response to ConA and P. gingivalis, suggesting chronic suppression of the anti
      inflammatory cytokine production. Blocking the proinflammatory cytokine response
      did not result in any substantial change in IL-10 or IL-4 response to live P.
      gingivalis. Blocking the proinflammatory cytokine response restored IL-10
      production by cells from CP in response to P. gingivalis lipopolysaccharide.
      CONCLUSIONS: These findings suggest that PBMCs from patients with CP have
      suppressed anti-inflammatory cytokine production that can, in part, be restored
      by neutralizing proinflammatory cytokines. Monocytes are an important source of
      IL-10 production, and monocyte-derived IL-10 might play a regulatory role in the
      pathogenesis of CP.

PMID- 23173825
TI  - Host genome, epigenome, and oral microbiome interactions: toward personalized
      periodontal therapy.
AB  - Periodontal diseases are multidimensional and complex. Bacterial content is the
      initiator, but disease progression depends on genetic and environmental
      parameters related to the host. Although bone loss magnitude is the common
      resulting outcome, the biologic process likely represents a unique inflammatory
      response characteristic to every individual. Therefore, it is obvious that
      practitioners must take into account the influence of these parameters and tailor
      a treatment accordingly. New, emerging deoxyribonucleotide-based technologies
      allow integration of the biologic impact of the environment, and periodontists
      should be prepared to incorporate these technologies into their practice to
      advance personalized medicine. This commentary provides updated insights on the
      distinctiveness of inflammation per individual in terms of microbiome and genome
      specificity and cites some educational resources helpful for implementing
      individualized therapy. 

PMID- 23173826
TI  - Effect of maxillary sinus membrane perforation on vital bone formation and
      implant survival: a retrospective study.
AB  - BACKGROUND: The maxillary sinus augmentation procedure (SAP) using the lateral
      window technique has been documented to be a highly predictable procedure.
      However, the most common intraoperative complication has been reported to be
      maxillary sinus membrane perforation (MSMP). The present study evaluates the
      percentage of vital bone and implant survival in sinuses that had perforations
      repaired during surgery versus a non-perforated sinus group. METHODS: Data were
      obtained retrospectively from an Institutional Review Board-approved anonymous
      database at New York University, Kriser Dental Center, Department of
      Periodontology and Implant Dentistry, New York, New York, from 23 patients who
      had undergone SAP with a total of 40 treated sinuses. Sinuses were grafted with
      mineralized cancellous bone allograft, anorganic bovine bone matrix, or biphasic
      calcium phospate. Perforation complications occurred in 15 sinuses with 25 non
      perforated sinuses. All perforations were repaired during surgery with absorbable
      collagen membrane barriers. Histologic cores were taken from all treated sinuses
      26 to 32 weeks after surgery. The implant success rate of 79 placed implants was
      recorded. RESULTS: The average percentage of vital bone was 26.3% +/- 6.3% in the
      perforated (repaired) sinuses versus 19.1% +/- 6.3% in the non-perforated
      sinuses. The differences were statistically significant (SS). The implant success
      rate was 100% (35 of 35) compared to 95.5% (43 of 45) in the perforated/repaired
      vs. non-perforated sinuses, respectively. There was no SS difference in implant
      failure rates. CONCLUSIONS: The augmented sinuses in this study that exhibited
      MSMPs that occurred during the SAP (which were treated during surgery) show SS
      greater vital bone percentages compared with the non-perforated sinus group.
      There were no SS differences in implant survival in the perforated versus non
      perforated groups. In this study, sinus MSMPs, when properly repaired during
      surgery, do not appear to be an adverse complication in terms of vital bone
      production or implant survival.

PMID- 23173827
TI  - Influence of periodontal status and periodontopathogens on levels of oral human
      beta-defensin-2 in saliva.
AB  - BACKGROUND: Expression patterns of human beta-defensin-2 (HBD-2) mRNA or HBD-2
      protein concentration and periodontal diseases have been a focus of scientific
      research. This study compares the salivary levels of HBD-2 protein concentration
      of healthy patients and patients with gingivitis and chronic periodontitis (CP)
      and correlates these levels with the presence of periodontopathogens. METHODS: A
      total of 89 patients were enrolled in this study: 31 periodontally healthy, 27
      with gingivitis, and 31 with CP. Plaque and gingival indices, probing depth, and
      clinical attachment level were measured. The presence of Campylobacter rectus,
      Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Tannerella
      forsythia, Treponema denticola, and Prevotella intermedia was evaluated
      qualitatively by conventional polymerase chain reaction. HBD-2 quantification in
      saliva was performed using an immune enzymatic assay. Frequency of
      periodontopathogens and HBD-2 protein concentration was assessed. Association
      between HBD-2 protein concentration (>=100 pg/mL) and the simultaneous presence
      of one to two, three to four, or five to six periodontopathogens was tested.
      RESULTS: Although periodontally healthy individuals and patients with gingivitis
      showed similar HBD-2 levels, the CP group displayed an increased level of HBD-2.
      P. gingivalis, P. intermedia, T. forsythia, and T. denticola were more prevalent
      in CP; however, their mere presence was not related to the increased levels of
      HBD-2 (Pearson correlation and multinomial logistic regression model).
      CONCLUSIONS: Salivary HBD-2 protein concentration was higher in patients with CP
      compared with healthy individuals or patients with gingivitis. These different
      protein concentrations were not related to the frequency of periodontopathogens.
      Clinical inflammatory profile had a higher impact on salivary HBD-2 levels than
      bacteria.

PMID- 23173828
TI  - The upregulation of transglutaminase-2 by cyclosporin a in human gingival
      fibroblasts is augmented by oxidative stress.
AB  - BACKGROUND: Transglutaminase-2 (TGM-2) has been implicated in several fibrotic
      disorders and can be induced by reactive oxygen species (ROS). Hence, the authors
      hypothesize that cyclosporin A (CsA) may regulate TGM-2 via ROS, and this
      regulation may have a role in the pathogenesis of CsA-induced gingival
      overgrowth. METHODS: Cytotoxicity, 2',7'-dichlorodihydrofluorescein diacetate
      assay, and Western blot were used to investigate the effects of CsA in human
      gingival fibroblasts (HGFs). In addition, extracellular signal-regulated kinase
      (ERK) inhibitor PD98059, phosphatidylinositol 3-kinase inhibitor LY294002,
      glutathione precursor N-acetyl-L-cysteine (NAC), curcumin, epigallocatechin-3
      gallate (EGCG), and p38 inhibitor SB203580 were added to find the possible
      regulatory mechanisms. RESULTS: Concentrations of CsA >500 ng/mL demonstrated
      cytotoxicity to HGFs (P < 0.05). CsA enhanced the generation of intracellular ROS
      at concentrations >200 ng/mL (P <0.05). TGM-2 protein induced by CsA was found in
      HGFs in a dose- and time-dependent manner (P <0.05). The addition of PD98059,
      LY294002, NAC, curcumin, EGCG, and SB203580 markedly inhibited TGM-2 expression
      induced by CsA (P <0.05). CONCLUSIONS: These results demonstrate that CsA
      significantly upregulates intracellular ROS generation and elevates TGM-2
      expression in HGFs. In addition, TGM-2 induced by CsA is downregulated by
      PD98059, LY294002, NAC, curcumin, EGCG, and SB203580.

PMID- 23173829
TI  - Predictive power of the severity measure of attachment loss for periodontal care
      need.
AB  - BACKGROUND: The prevalence of periodontal diseases is high, and >15% of adults
      have severe gum disease. Clinical attachment loss (AL) is one of the most
      important measures for periodontal disease severity. With AL, one could measure
      the worst scenario, the average, or the cumulative sum of AL among all teeth. The
      objective of this study is to evaluate which of the 15 measures of periodontal
      problems (e.g., maximum, mean, and cumulative AL) best predict the need for
      periodontal treatment. METHODS: Using detailed periodontal data obtained through
      clinical examination from the National Health and Nutrition Examination Survey
      1999 to 2002, weighted logistic regression was used to model the periodontal
      treatment need of 15 different periodontal disease measures. The outcome measure
      is the clinically determined periodontal need. RESULTS: After adjustment for the
      covariates of age, sex, ethnicity, education, smoking status, and diabetes, the
      three most predictive measures were identified as: 1) the sum of the maximum mid
      buccal (B) and mesio-buccal (MB) measures, which reflects the worst case of both
      B and MB measures; 2) the sum of the maximum MB measure or the worst case of the
      MB measure; and 3) the sum of all B and MB measures, or the cumulative AL
      measures. CONCLUSIONS: Cumulative periodontal morbidity, particularly the worst
      case of B and MB measures, has the strongest impact on the need for periodontal
      care. All the demographic variables and covariates follow the classic pattern of
      association with periodontal disease.

PMID- 23173832
TI  - Persistence of Mycobacterium bovis bacillus Calmette-Guerin (BCG) Danish in white
      tailed deer (Odocoileus virginianus) vaccinated with a lipid-formulated oral
      vaccine.
AB  - Mycobacterium bovis, the causative agent of tuberculosis in animals, has a broad
      host range, including humans. Historically, public health concerns prompted
      programs to eradicate tuberculosis from cattle in many nations. Eradication
      efforts decreased the prevalence of bovine tuberculosis; nevertheless, some
      countries encountered significant obstacles, not least of which was a wildlife
      reservoir of M. bovis. Efforts to decrease the size of the affected wildlife
      populations have neither eliminated disease nor eliminated transmission to
      cattle. Consequently, the use of a vaccine for wildlife is being explored. The
      vaccine most studied is M. bovis BCG, an attenuated live vaccine, first developed
      100 years ago. The most efficient and effective means of vaccinating wildlife
      will be an oral vaccine. White-tailed deer in Michigan, USA, constitute a
      reservoir of M. bovis. White-tailed deer are a popular game species, and as such,
      represent a food animal to many hunters. BCG persistence in deer tissues could
      result in human exposure to BCG. Although non-pathogenic, BCG exposure could
      induce false-positive skin test results, confounding the central component of
      public health surveillance for TB. The objective of the present study in white
      tailed deer was to evaluate persistence of lipid-encapsulated BCG and a liquid
      suspension of BCG after oral administration at two different dosages. Vaccine was
      not recovered at any time after oral consumption of a bait containing a single
      dose (1 * 10(8) CFU) of lipid-encapsulated BCG. However, persistence was
      consistent in deer consuming 10 lipid-encapsulated baits (1 * 10(9) CFU), with
      BCG recovered from at least one deer at 1, 3, 6, 9 and 12 months after
      consumption. Persistence of up to 9 months was seen in deer vaccinated with
      orally with a liquid suspension. Persistence of BCG was limited to lymphoid
      tissue and never found in samples of muscle collected at each time point.
      Although the risk of exposure to hunters is low, BCG persistence should be
      considered prior to field use in white-tailed deer.

PMID- 23173831
TI  - Effects of supplementation with n-3 polyunsaturated fatty acids on cognitive
      performance and cardiometabolic risk markers in healthy 51 to 72 years old
      subjects: a randomized controlled cross-over study.
AB  - BACKGROUND: Higher plasma n-3 polyunsaturated fatty acids (PUFA) have been
      associated with a lower risk of age related cognitive decline, and to
      beneficially affect cardiometabolic risk factors. A relation exists between
      metabolic disorders such as diabetes type 2 and cognitive decline. Results
      regarding the potential effects of n-3 PUFA on risk factors in healthy subjects
      are divergent, and studies regarding the possible relation between
      cardiometabolic parameters and cognitive performance are scarce. The objective
      was to evaluate the effects of five weeks intake of long chain n-3 PUFA on
      cognitive performance in healthy individuals, and to exploit the possible
      relation between outcomes in cognitive tests to cardiometabolic risk parameters.
      METHODS: Fish oil n-3 PUFA (3g daily) were consumed during 5 weeks separated by a
      5 week washout period in a cross-over placebo controlled study, including 40
      healthy middle aged to elderly subjects. Cognitive performance was determined by
      tests measuring working memory (WM) and selective attention. RESULTS:
      Supplementation with n-3 PUFA resulted in better performance in the WM-test
      compared with placebo (p < 0.05). In contrast to placebo, n-3 PUFA lowered plasma
      triacylglycerides (P < 0.05) and systolic blood pressure (p < 0.0001). Systolic
      blood pressure (p < 0.05), f-glucose (p = 0.05), and s-TNF-alpha (p = 0.05), were
      inversely related to the performance in cognitive tests. CONCLUSIONS: Intake of n
      3 PUFA improved cognitive performance in healthy subjects after five weeks
      compared with placebo. In addition, inverse relations were obtained between
      cardiometabolic risk factors and cognitive performance, indicating a potential of
      dietary prevention strategies to delay onset of metabolic disorders and
      associated cognitive decline.

PMID- 23173830
TI  - Problem-solving versus cognitive restructuring of medically ill seniors with
      depression (PROMISE-D trial): study protocol and design.
AB  - BACKGROUND: With an ageing population in most Western countries, people are
      living longer but often with one or more chronic physical health problems. Older
      people in physically poor health are at greater risk of developing clinical
      depression. Cognitive Behavioural Therapy (CBT) and Problem Solving Therapy (PST)
      have both been found to be efficacious in treating late-life depression, however
      patients with "multi-morbidity" (i.e. more than one chronic condition) are often
      excluded from these trials. The aim of this study is to compare the efficacy of
      CBT and PST in treating older adults who have one or more chronic physical health
      conditions and a diagnosable depressive disorder. This study will be the first to
      explicitly target the treatment of depression in older people in primary care
      settings presenting with a range of health problems using behavioural
      interventions. METHODS/DESIGN: The PROMISE-D study is a randomised controlled
      trial of two evidence-based treatments for late-life major or minor depression
      for patients who also have at least one co-morbid chronic health problem.
      Participants will be randomised to two active interventions (PST or CBT) or
      enhanced treatment-as-usual (E-TAU). Primary outcomes will be depression
      diagnostic status and severity of depression (according to the Hamilton
      Depression Rating Scale and the Geriatric Depression Scale). Secondary outcomes
      will be anxiety severity, quality of life and health care utilisation.
      Assessments will be conducted by a researcher who remains blind to the patient's
      treatment allocation and will be conducted pre and post-treatment and at six and
      12 months follow-up. Health care utilisation will be assessed throughout a two
      year period following entry to the trial. Executive function, rumination and
      emotion regulation will also be measured to determine the impact of these factors
      on treatment response in two treatment groups. DISCUSSION: Multi-morbidity, the
      experience of two or more chronic health problems, is becoming an increasing
      problem internationally, particularly amongst the elderly. Evidence-based
      psychological treatments exist for late-life depression and these have been shown
      to be effective for participants with individual health problems and depression.
      However, there are no studies that have compared the two leading psychotherapies
      shown to be effective in the treatment of late-life depression. In addition, many
      trials of psychotherapy with older adults exclude those with multi-morbidity.
      Hence, this trial will confirm whether CBT and PST are efficacious in the
      treatment of depression in the context of complex medical needs and determine
      which of these two interventions is most efficacious. TRIAL REGISTRATION:
      ACTRN12612000854831.

PMID- 23173833
TI  - Effect of conformation sampling strategies in genetic algorithm for multiple
      protein docking.
AB  - BACKGROUND: Macromolecular protein complexes play important roles in a cell and
      their tertiary structure can help understand key biological processes of their
      functions. Multiple protein docking is a valuable computational tool for
      providing structure information of multimeric protein complexes. In a previous
      study we developed and implemented an algorithm for this purpose, named Multi
      LZerD. This method represents a conformation of a multimeric protein complex as a
      graph, where nodes denote subunits and each edge connecting nodes denotes a
      pairwise docking conformation of the two subunits. Multi-LZerD employs a genetic
      algorithm to sample different topologies of the graph and pairwise
      transformations between subunits, seeking for the conformation of the optimal
      (lowest) energy. In this study we explore different configurations of the genetic
      algorithm, namely, the population size, whether to include a crossover operation,
      as well as the threshold for structural clustering, to find the optimal
      experimental setup. METHODS: Multi-LZerD was executed to predict the structures
      of three multimeric protein complexes, using different population sizes,
      clustering thresholds, and configurations of mutation and crossover. We analyzed
      the impact of varying these parameters on the computational time and the
      prediction accuracy. RESULTS AND CONCLUSIONS: Given that computational resources
      is a key for handling complexes with a large number of subunits and also for
      computing a large number of protein complexes in a genome-scale study, finding a
      proper setting for sampling the conformation space is of the utmost importance.
      Our results show that an excessive sampling of the conformational space by
      increasing the population size or by introducing the crossover operation is not
      necessary for improving accuracy for predicting structures of small complexes.
      The clustering is effective in reducing redundant pairwise predictions, which
      leads to successful identification of near-native conformations.

PMID- 23173834
TI  - Consenting options for posthumous organ donation: presumed consent and incentives
      are not favored.
AB  - BACKGROUND: Posthumous organ procurement is hindered by the consenting process.
      Several consenting systems have been proposed. There is limited information on
      public relative attitudes towards various consenting systems, especially in
      Middle Eastern/Islamic countries. METHODS: We surveyed 698 Saudi Adults attending
      outpatient clinics at a tertiary care hospital. Preference and perception of norm
      regarding consenting options for posthumous organ donation were explored.
      Participants ranked (1, most agreeable) the following, randomly-presented,
      options from 1 to 11: no-organ-donation, presumed consent, informed consent by
      donor-only, informed consent by donor-or-surrogate, and mandatory choice; the
      last three options +/- medical or financial incentive. RESULTS: Mean(SD) age was
      32(9) year, 27% were males, 50% were patients' companions, 60% had >= college
      education, and 20% and 32%, respectively, knew an organ donor or recipient.
      Mandated choice was among the top three choices for preference of 54% of
      respondents, with an overall median[25%,75%] ranking score of 3[2,6], and was
      preferred over donor-or-surrogate informed consent (4[2,7], p < 0.001), donor
      only informed consent (5[3,7], p < 0.001), and presumed consent (7[3,10], p <
      0.001). The addition of a financial or medical incentive, respectively, reduced
      ranking of mandated choice to 7[4,9], p < 0.001, and 5[3,8], p < 0.001; for donor
      or-surrogate informed consent to 7[5,9], p < 0.001, and 5[3,7], p = 0.004; and
      for donor-only informed consent to 8[6,10], p < 0.001, and 5[3,7], p = 0.56.
      Distribution of ranking score of perception of norm and preference were similar
      except for no-organ donation (11[7,11] vs. 11[6,11], respectively, p = 0.002).
      Compared to females, males more perceived donor-or-surrogate informed consent as
      the norm (3[1,6] vs. 5[3,7], p < 0.001), more preferred mandated choice with
      financial incentive option (6[3,8] vs. 8[4,9], p < 0.001), and less preferred
      mandated choice with medical incentive option (7[4,9] vs. 5[2,7], p < 0.001).
      There was no association between consenting options ranking scores and age,
      health status, education level, or knowing an organ donor or recipient.
      CONCLUSIONS: We conclude that: 1) most respondents were in favor of posthumous
      organ donation, 2) mandated choice system was the most preferred and presumed
      consent system was the least preferred, 3) there was no difference between
      preference and perception of norm in consenting systems ranking, and 4) financial
      (especially in females) and medical (especially in males) incentives reduced
      preference.

PMID- 23173835
TI  - Vancomycin-resistant enterococcal meningitis in an autologous stem cell
      transplant recipient cured with linezolid.
AB  - Enterococci are an unusual cause of meningitis, with most cases reported in the
      literature preceded by neurosurgical procedures. Spread to the meninges from an
      enterococcal bloodstream infection is even more rare, with few cases reported in
      the literature. We report the first documented case, to our knowledge, of
      successful treatment of vancomycin-resistant enterococcal (VRE) meningitis with
      linezolid therapy in an immunosuppressed hematopoietic stem cell transplant
      recipient. Our case highlights the success of monotherapy with linezolid for VRE
      meningitis. A literature review is provided, which reveals that there is little
      evidenced-based data on the optimal therapy for VRE meningitis.

PMID- 23173836
TI  - Depression in older breast cancer survivors.
AB  - BACKGROUND: Breast cancer is the most commonly diagnosed cancer among U.S. women
      .The 5-year survival rate for this tumour is nowadays 85%, and the 61% of these
      women are still alive at 15 years. When depression symptoms are present as a
      consequence of breast cancer treatments, they may interfere negatively with
      patients' quality of life. The aim of this study was to examine the effects of
      breast cancer treatment on the quality of life and the impact of depression on
      the health-related life. METHODS: We enrolled 173 women aged 65-75 years with
      early stage breast cancer diagnosed over the last 10 years, initially recruited
      to participate in a study examining heath-related quality of life in the first 5
      years after breast cancer diagnosis. Participants were divided into four groups:
      1) 46 breast cancer survivors (aged 65-70); 2) 62 women diagnosed with breast
      cancer (aged 65-69); 3) 32 women with recurrent breast cancer after 10 years
      (aged 66-75); 4) 30 women in good health status (aged 60-70). The Geriatric
      Depression Scale was used as a routine part of a comprehensive geriatric
      assessment. Collection of data for the application of instruments, such as
      sociodemographic variables (age, educational level, social state) and clinical
      date (stage and time of the disease and treatment), was carried out by trained
      researcher assistants. RESULTS: Our results demonstrated the correlation between
      depression and previous cancer experiences. In fact, in patients with cancer
      experience, the grade of depression was significantly higher compared to healthy
      subjects. Furthermore, we demonstrated that the patients with recurrent breast
      cancer were severely depressed compared to other groups. CONCLUSIONS: A high
      percentage of participants were identified as having emotional and/or well being
      problems. Further investigations on the cause of depression problems cancer
      related are needed.

PMID- 23173837
TI  - Papillary glioneuronal tumour: a review of the literature with two illustrative
      cases.
AB  - We report two cases of papillary glioneuronal tumour (PGNT). One was located in
      the supratentorial parenchyma and the other was intraventricular. Both patients
      underwent gross total resection of their tumour and have returned to normal
      lifestyle. Papillary glioneuronal tumor is a recently described rare cerebral
      neoplasm. Recently classified by the World Health Organization in 2007 as a Grade
      I neuronal-glial tumour, these tumours are infrequent lesions that can be
      challenging to the practising pathologist. Patients commonly present with
      headaches or seizures, but may be asymptomatic with the mass discovered
      incidentally. The characteristic radiological, histological and
      immunohistochemical features are discussed. Surgical excision has been curative
      in most of the cases with only a handful of cases of recurrence reported. The
      increasing number of reports in the literature shows how PGNT forms a good
      example of a newly diagnosed tumour category in evolution. New classifications
      and re-classifications of broad categories of brain tumours will hopefully lead
      to a narrower diagnostic, prognostic and therapeutic profile. The even rarer
      presence of atypia calls for longer follow-up to help elucidate further its
      biological behaviour.

PMID- 23173838
TI  - Assessment of anodized titanium implants bioactivity.
AB  - OBJECTIVES: This study was conducted to create nanostructured surface titanium
      implants by anodic oxidation process aiming to bring out bioactivity and to
      assess the resultant bioactivity both in vitro and in vivo. MATERIALS AND
      METHODS: An economic protocol was used to apply anodic spark discharge and create
      surface nanoporosities on grade II commercially pure titanium (cpTi). The in
      vitro investigation included morphology, surface chemical analysis, roughness and
      crystalline structure of titanium oxide (TiO2) film prepared. Assessment of the
      bioactivity was carried out by immersing the specimens in simulate body fluid
      (SBF) and investigating the surface-deposited layer. The in vivo investigation
      was conducted by surgically placing the anodized implants into rabbits tibia for
      different healing periods. Then biomechanical evaluation was performed to verify
      the effect of treatments on the interface resistance to shear force. Routine
      histological analysis was performed to evaluate the bone tissue reactions to
      anodized implants. RESULTS: Anodization of titanium implants produced
      morphological changes, raised the percentage of oxygen in the TiO2 layer,
      increased surface area and roughness of implants remarkably, and modified the
      crystallinity of the film. The in vitro assessments of bioactivity showed that a
      layer of calcium phosphate was precipitated on the titanium surfaces 7 days after
      soaking into SBF. The implant-bone interface resistance to shear force was
      enhanced at 2-week healing period. This was confirmed by histological findings.
      CONCLUSION: Nanostructured surface titanium implants could be prepared by anodic
      oxidation with resultant accelerated bioactivity that may be recommended for
      early loading.

PMID- 23173839
TI  - Sleep-Wake profiles in patients with primary biliary cirrhosis.
AB  - BACKGROUND: Impaired sleep quality and daytime sleepiness have been described in
      patients with primary biliary cirrhosis (PBC). However, no information is
      available on their sleep timing/diurnal preference. AIMS: To evaluate such
      variables and determine their relationship with sleep quality, fatigue, pruritus
      and quality of life. METHODS: Seventy-four patients with PBC (58 +/- 12 years),
      79 healthy volunteers (56 +/- 8 years) and 60 patients with cirrhosis (58 +/- 12
      years) underwent formal assessment of sleep quality/timing, diurnal preference
      and daytime sleepiness. Patients with PBC also underwent assessment of fatigue,
      quality of life and the daytime course of sleepiness/pruritus. RESULTS: Sleep
      timing was significantly delayed in both patients with PBC and with cirrhosis,
      compared to healthy volunteers (sleep onset time: 23:18 +/- 01:00 vs. 23:30 +/-
      01:00 vs. 22:54 +/- 00:54 hours, respectively; P < 0.05). In patients with PBC,
      delayed sleep timing was associated with impaired sleep quality (P < 0.05).
      Sleepiness showed a physiological daily rhythm, with early afternoon/evening
      peaks. Pruritus was absent in the morning and increased over the
      afternoon/evening hours. Both the daytime course of pruritus and sleepiness
      changed in relation to diurnal preference. Patients with PBC and significant
      pruritus (upper quartile) had prolonged sleep latency (39 +/- 37 vs. 21 +/- 23
      min, P = 0.05) and earlier wake-up times (5.9 +/- 0.8 vs. 6.7 +/- 0.9 min, P <
      0.05). Significant correlations were observed between sleep timing and quality of
      life. CONCLUSIONS: Patients with PBC exhibited a delay in sleep timing that was
      associated with impaired sleep quality/quality of life. In addition, an interplay
      was observed between diurnal preference and the daytime course of
      pruritus/sleepiness.

PMID- 23173840
TI  - Epidemiological and economic trends in inpatient and outpatient thyroidectomy in
      the United States, 1996-2006.
AB  - BACKGROUND: Traditionally, thyroid surgery has been an inpatient procedure due to
      the risk of several well-documented complications. Recent research suggests that
      for selected patients, outpatient thyroid surgery is safe and feasible, with the
      additional potential benefit of cost savings. In recognition of these
      observations, we hypothesized that there would be an increase in U.S. outpatient
      thyroidectomies with a concurrent decline in inpatient thyroidectomies over time.
      METHODS: Comparative cross-sectional analyses of the National Survey of
      Ambulatory Surgery (NSAS) and Nationwide Inpatient Sample (NIS) databases from
      1996 and 2006 were performed. All cases of thyroid surgery were extracted, as
      well as data on age, sex, and insurance status. Diagnoses and surgical cases were
      identified using International Classification of Diseases, Ninth Revision (ICD-9)
      diagnostic and treatment codes. Hospital charges were acquired from the NIS 1996
      and 2006 and NSAS 2006 releases, using imputed data where necessary. After survey
      weights were applied, patient characteristics, diagnoses, and procedures were
      compared for inpatient versus outpatient procedures. RESULTS: The total number of
      thyroidectomies increased 39%, from 66,864 to 92,931 cases per year during the
      study timeframe. Outpatient procedures increased by 61%, while inpatient
      procedures increased by 30%. The proportion of privately insured inpatients
      declined slightly from 63.8% to 60.1%, while those covered by Medicare increased
      from 22.8% to 25.8%. In contrast, the proportion of privately insured outpatients
      declined sharply from 76.8% to 39.9%, while those covered by Medicare rose from
      17.2% to 45.7%. These trends coincided with a small increase in the mean
      inpatient age from 50.2 to 52.3 years and a larger increase in the mean
      outpatient age from 50.7 to 58.1 years. Inflation-adjusted per-capita charges for
      inpatient thyroidectomies more than doubled from $9,934 in 1996 to $22,537 in
      2006, while aggregate national inpatient charges tripled from $464 million to
      $1.37 billion. By comparison, per-capita charges for outpatient thyroidectomy
      totaled $7,222 in 2006. CONCLUSIONS: From 1996 to 2006, there has been a
      concurrent modest increase in inpatient and pronounced increase in outpatient
      thyroidectomies in the United States, with a consequential demographic shift and
      economic impact.

PMID- 23173841
TI  - Proton transfer reactions of triazol-3-ylidenes: kinetic acidities and carbon
      acid pKa values for twenty triazolium salts in aqueous solution.
AB  - Second-order rate constants have been determined for deuteroxide ion-catalyzed
      exchange of the C(3)-proton for deuterium, k(DO) (M(-1) s(-1)), of a series of 20
      triazolium salts in aqueous solution at 25  degrees C and ionic strength I = 1.0
      (KCl). Evidence is presented that the rate constant for the reverse protonation
      of the triazol-3-ylidenes by solvent water is close to that for dielectric
      relaxation of solvent (10(11) s(-1)). These data enabled the calculation of
      carbon acid pK(a) values in the range 16.5-18.5 for the 20 triazolium salts. pD
      rate profiles for deuterium exchange of the triazolium salts reveal that
      protonation at nitrogen to give dicationic triazolium species occurs under acidic
      conditions, with estimates of pK(a)(N1) = -0.2 to 0.5.

PMID- 23173843
TI  - Elevated serum levels of Chromogranin A in hepatocellular carcinoma.
AB  - BACKGROUND: During the past three decades, the incidence of hepatocellular
      carcinoma in the United States has tripled. The neuroendocrine character has been
      observed in some tumor cells within some hepatocellular carcinoma nodules and
      elevated serum chromogranin A also been reported in patients with hepatocellular
      carcinoma. The aim of this work was to investigate the role of serum
      concentration of chromogranin A in patients with hepatocellular carcinoma at
      different stages. METHODS: The study population consisted of 96 patients (63
      males and 33 females age range 52-84) at their first hospital admission for
      hepatocellular carcinoma. The control group consisted of 35 volunteers (20 males
      and 15 females age range 50-80). The hepatocellular carcinoma patients were
      stratified according the Barcelona-Clinic Liver Cancer classification. Venous
      blood samples were collected before treatment from each patients before surgery,
      centrifuged to obtain serum samples and stored at -80 degrees  C until assayed.
      RESULTS: The chromogranin A serum levels were elevated (> 100 ng/ml) in 72/96
      patients with hepatocellular carcinoma. The serum levels of chromogranin A were
      significantly correlated (p<0.05) with alpha-fetoprotein. In comparison with
      controls, the hepatocellular carcinoma patients showed a significant increase
      (p<0.001) vs controls. The chromogranin A levels in the Barcelona staging of
      hepatocellular carcinoma was higher in stage D compared to stage C (p<0.01), to
      stage B (p<0.001), and to stage A (p<0.001). CONCLUSIONS: Molecular markers, such
      as chromogranin A, could be very useful tools for hepatocellular carcinoma
      diagnosis. However the molecular classification should be incorporated into a
      staging scheme, which effectively separated patients into groups with homogeneous
      prognosis and response to treatment, and thus serves to aid in the selection of
      appropriate therapy.

PMID- 23173842
TI  - Targeting the Bcl-2 family for cancer therapy.
AB  - INTRODUCTION: Programmed cell death is well-orchestrated process regulated by
      multiple pro-apoptotic and anti-apoptotic genes, particularly those of the Bcl-2
      gene family. These genes are well documented in cancer with aberrant expression
      being strongly associated with resistance to chemotherapy and radiation. AREAS
      COVERED: This review focuses on the resistance induced by the Bcl-2 family of
      anti-apoptotic proteins and current therapeutic interventions currently in
      preclinical or clinical trials that target this pathway. Major resistance
      mechanisms that are regulated by Bcl-2 family proteins and potential strategies
      to circumvent resistance are also examined. Although antisense and gene therapy
      strategies are used to nullify Bcl-2 family proteins, recent approaches use small
      molecule inhibitors (SMIs) and peptides. Structural similarity of the Bcl-2
      family of proteins greatly favors development of inhibitors that target the BH3
      domain, called BH3 mimetics. EXPERT OPINION: Strategies to specifically identify
      and inhibit critical determinants that promote therapy resistance and tumor
      progression represent viable approaches for developing effective cancer
      therapies. From a clinical perspective, pretreatment with novel, potent Bcl-2
      inhibitors either alone or in combination with conventional therapies hold
      significant promise for providing beneficial clinical outcomes. Identifying SMIs
      with broader and higher affinities for inhibiting all of the Bcl-2 pro-survival
      proteins will facilitate development of superior cancer therapies.

PMID- 23173845
TI  - Clinical involvement and transparency in medical apps; not all apps are equal.

PMID- 23173844
TI  - PXR and CAR single nucleotide polymorphisms influence plasma efavirenz levels in
      South African HIV/AIDS patients.
AB  - BACKGROUND: This study investigated variation in NR1I2 and NR1I3 and its effect
      on plasma efavirenz levels in HIV/AIDS patients. Variability in plasma drug
      levels has largely led research on identifying causative variants in drug
      metabolising enzyme (DME) genes, with little focus on the nuclear receptor genes
      NR1I2 and NR1I3, coding for PXR and CAR, respectively, that are involved in
      regulating DMEs. METHODS: 464 Bantu-speaking South Africans comprising of
      HIV/AIDS patients on efavirenz-based treatment (n=301) and 163 healthy subjects
      were genotyped for 6 SNPs in NR1I2 and NR1I3. 32 of the 301 patients had their
      DNA binding domains (DBDs) in NR1I2 and NR1I3 sequenced. RESULTS: Significantly
      decreased efavirenz plasma concentrations were observed in patients carrying the
      NR1I3 rs3003596C/C and T/C genotypes (P=0.015 and P=0.010, respectively).
      Sequencing resulted in the discovery of a further 13 SNPs, 3 of which are novel
      variants in the DBD of NR1I2. There were significant differences in the
      distribution of NR1I2 and NR1I3 SNPs between South Africans when compared to
      Caucasian, Asian and Yoruba population groups. CONCLUSION: For the realisation of
      personalised medicine, PXR and CAR genetic variation should be taken into
      consideration because of their involvement in the regulation of DMEs.

PMID- 23173846
TI  - Local recurrence of gastric cancer after total gastrectomy: an unusual
      presentation.
AB  - A 71 years old Italian man had type 3 gastric cancer of the greater curvature.
      Total gastrectomy with splenectomy and D2 lymph node dissection were performed.
      After discharge chemotherapy ELF regimen was administered for 6 months. After 16
      months from the operation a local recurrence was discovered by CT scan. Surgical
      en-bloc resection was performed removing pancreatic tail, splenic colic flexure
      and a portion of left diaphragm. Histological examination confirmed local
      recurrence of gastric adenocarcinoma infiltrating pancreas, colon and diaphragm
      with lymph node metastasis.

PMID- 23173847
TI  - Soft tissue injuries of the tarsocrural joint: a retrospective analysis of 30
      cases evaluated arthroscopically.
AB  - REASONS FOR PERFORMING THE STUDY: Intra-articular soft tissue injuries of the
      equine tarsocrural joint have been poorly defined. METHODS: All horses that
      underwent arthroscopic surgery of a tarsocrural joint over a 10 year period were
      identified. Those with primary intra-articular soft tissue injuries were selected
      for inclusion and the cases evaluated retrospectively. RESULTS: Two hundred and
      eighty-one horses underwent tarsocrural joint arthroscopy during the study
      period, 30 of which met the inclusion criteria (30 joints). A combination of soft
      tissue lesions was more common than injury to a single structure. Injuries
      involved the joint capsule (n = 25), collateral ligaments (n = 20), dorsal plica
      (n = 8) and open communication between the tarsocrural joint and extensor bundle
      (n = 7). Following arthroscopic surgery and rehabilitation, 81% of horses were
      able to return to their previous function. CONCLUSION: Intra-articular soft
      tissue injuries of the tarsocrural joint may be associated with localising
      clinical signs of inflammation. This series represented 11% of the total number
      of arthroscopic procedures undertaken on that joint in a single referral
      hospital. Arthroscopic surgery allows accurate definition of the injuries and
      facilitates lesion management. Case outcome following arthroscopic debridement
      and a subsequent period of rehabilitation is favourable. POTENTIAL RELEVANCE: In
      lame horses with clinical signs localised to the tarsocrural joint, disrupted
      intra-articular soft tissues should be considered in the list of differential
      diagnoses. Attending clinicians should consider arthroscopic evaluation in cases
      where primary intra-articular soft tissue injuries are suspected to be causative.

PMID- 23173848
TI  - Evaluating the predictive value of biomarkers with stratified case-cohort design.
AB  - Identification of novel biomarkers for risk assessment is important for both
      effective disease prevention and optimal treatment recommendation. Discovery
      relies on the precious yet limited resource of stored biological samples from
      large prospective cohort studies. Case-cohort sampling design provides a cost
      effective tool in the context of biomarker evaluation, especially when the
      clinical condition of interest is rare. Existing statistical methods focus on
      making efficient inference on relative hazard parameters from the Cox regression
      model. Drawing on recent theoretical development on the weighted likelihood for
      semiparametric models under two-phase studies (Breslow and Wellner, 2007), we
      propose statistical methods to evaluate accuracy and predictiveness of a risk
      prediction biomarker, with censored time-to-event outcome under stratified case
      cohort sampling. We consider nonparametric methods and a semiparametric method.
      We derive large sample properties of proposed estimators and evaluate their
      finite sample performance using numerical studies. We illustrate new procedures
      using data from Framingham Offspring Study to evaluate the accuracy of a recently
      developed risk score incorporating biomarker information for predicting
      cardiovascular disease.

PMID- 23173850
TI  - Effect of periodic number of [Si/Sb80Te20]x multilayer film on its laser-induced
      crystallization studied by coherent phonon spectroscopy.
AB  - The periodic number dependence of the femtosecond laser-induced crystallization
      threshold of [Si(5nm)/Sb80Te20(5nm)]x nanocomposite multilayer films has been
      investigated by coherent phonon spectroscopy. Coherent optical phonon spectra
      show that femtosecond laser-irradiated crystallization threshold of the
      multilayer films relies obviously on the periodic number of the multilayer films
      and decreases with the increasing periodic number. The mechanism of the periodic
      number dependence is also studied. Possible mechanisms of reflectivity and
      thermal conductivity losses as well as the effect of the glass substrate are
      ruled out, while the remaining superlattice structure effect is ascribed to be
      responsible for the periodic number dependence. The sheet resistance of
      multilayer films versus a lattice temperature is measured and shows a similar
      periodic number dependence with one of the laser irradiation crystallization
      power threshold. In addition, the periodic number dependence of the
      crystallization temperature can be fitted well with an experiential formula
      obtained by considering coupling exchange interactions between adjacent layers in
      a superlattice. Those results provide us with the evidence to support our
      viewpoint. Our results show that the periodic number of multilayer films may
      become another controllable parameter in the design and parameter optimization of
      multilayer phase change films.

PMID- 23173849
TI  - Inclusion of mobile phone numbers into an ongoing population health survey in New
      South Wales, Australia: design, methods, call outcomes, costs and sample
      representativeness.
AB  - BACKGROUND: In Australia telephone surveys have been the method of choice for
      ongoing jurisdictional population health surveys. Although it was estimated in
      2011 that nearly 20% of the Australian population were mobile-only phone users,
      the inclusion of mobile phone numbers into these existing landline population
      health surveys has not occurred. This paper describes the methods used for the
      inclusion of mobile phone numbers into an existing ongoing landline random digit
      dialling (RDD) health survey in an Australian state, the New South Wales
      Population Health Survey (NSWPHS). This paper also compares the call outcomes,
      costs and the representativeness of the resultant sample to that of the previous
      landline sample. METHODS: After examining several mobile phone pilot studies
      conducted in Australia and possible sample designs (screening dual-frame and
      overlapping dual-frame), mobile phone numbers were included into the NSWPHS using
      an overlapping dual-frame design. Data collection was consistent, where possible,
      with the previous years' landline RDD phone surveys and between frames. Survey
      operational data for the frames were compared and combined. Demographic
      information from the interview data for mobile-only phone users, both, and total
      were compared to the landline frame using chi2 tests. Demographic information for
      each frame, landline and the mobile-only (equivalent to a screening dual frame
      design), and the frames combined (with appropriate overlap adjustment) were
      compared to the NSW demographic profile from the 2011 census using chi2 tests.
      RESULTS: In the first quarter of 2012, 3395 interviews were completed with 2171
      respondents (63.9%) from the landline frame (17.6% landline only) and 1224
      (36.1%) from the mobile frame (25.8% mobile only). Overall combined response,
      contact and cooperation rates were 33.1%, 65.1% and 72.2% respectively. As
      expected from previous research, the demographic profile of the mobile-only phone
      respondents differed most (more that were young, males, Aboriginal and Torres
      Strait Islanders, overseas born and single) compared to the landline frame
      responders. The profile of respondents from the two frames combined, with overlap
      adjustment, was most similar to the latest New South Wales (NSW) population
      profile. CONCLUSIONS: The inclusion of the mobile phone numbers, through an
      overlapping dual-frame design, did not impact negatively on response rates or
      data collection, and although costing more the design was still cost-effective
      because of the additional interviews that were conducted with young people,
      Aboriginal and Torres Strait Islanders and people who were born overseas
      resulting in a more representative overall sample.

PMID- 23173853
TI  - Prognostic value of pulmonary hypertension in patients undergoing surgery for
      degenerative mitral valve disease with leaflet prolapse.
AB  - BACKGROUND AND AIM OF THE STUDY: The aim of this study was to evaluate the impact
      of pulmonary hypertension (PH) on early and late outcomes following surgery in
      patients with degenerative mitral regurgitation. METHODS: The study included 270
      patients who had undergone isolated mitral valve surgery (MVS) for leaflet
      prolapse during 1998 to 2010. Pulmonary artery systolic pressure (PASP) was
      measured with Doppler echocardiography pre- and postoperatively. The impact of PH
      (PASP > 50 mmHg) on mortality and the potential for postoperative resolution of
      preoperatively elevated PASP was retrospectively analyzed. RESULTS: The incidence
      of PH was 27% (n = 74/270). Postoperative normalization, or reduction of
      preoperative PASP, was demonstrated in 87% of the patients with PH at a median of
      two months (interquartile range 1 to 19). Absent improvement or a postoperative
      increase in PASP was independently predicted by age (OR 1.08, 95% CI 1.02-1.14, p
      = 0.010). Preoperative PH resulted in a fourfold higher risk of postoperative
      mortality (HR 4.3, 95% CI 1.1-17.4, p = 0.039) during the first three years of
      follow-up. CONCLUSIONS: PH is an independent predictor of mortality during the
      initial three years following MVS. The majority of patients with PH demonstrated
      a reduction of preoperatively elevated PASP following surgery and the increased
      risk of mortality gradually decreased after three years. Our findings support
      early admission for mitral valve surgery before the occurrence of PH.

PMID- 23173852
TI  - Influence of chronic total occlusions on coronary artery bypass graft surgical
      outcomes.
AB  - BACKGROUND: Presence of epicardial coronary artery chronic total occlusion (CTO)
      predicts higher referral rates for coronary bypass graft surgery (CABG). However,
      the impact of coronary artery CTO on CABG outcomes has never been systematically
      studied. METHOD: We examined one-year outcomes in 605 consecutive Veterans,
      discharged post-CABG between June 2005 and December 2008. RESULTS: A coronary CTO
      was present in 256 patients (42%), predominantly (48.3%) in the right coronary
      artery distribution. Baseline clinical characteristics and medical therapy were
      similar in patients with and without a coronary CTO. A single CTO was present in
      73.8%, and 26.2% patients had multiple CTO. All left anterior descending coronary
      artery CTO were successfully bypassed, as were >92% in left circumflex and right
      coronary arteries and 85% CTO in multiple coronary artery distributions. During
      the mean follow-up of 348.9 +/- 4.5 days, incidence of all-cause death and
      myocardial infarction were similar in both groups (7.1% in CTO group and 7.4% in
      non-CTO group; p = 0.97). CTO >20 mm in length constituted 74.9% and >40 mm
      37.8%. One-year survival post-CABG was significantly lower in patients with CTO
      lengths >40 mm compared to <=20 mm (p = 0.04). CTO >40 mm was an independent
      predictor of post-CABG mortality controlling for age, number of CTO, comorbid
      diseases, clopidogrel use, severity of coronary artery disease, renal failure,
      and left ventricular ejection fraction. CONCLUSION: CABG achieves high success in
      grafting epicardial coronary vessels with CTO; however, presence of long coronary
      CTO (>40 mm) is an independent predictor of post-CABG survival.

PMID- 23173854
TI  - On-pump transcatheter aortic valve replacement in patients with poor left
      ventricular function.
AB  - Transcatheter aortic valve replacement (TAVR) has recently been shown to be
      feasible in patients with severe aortic stenosis who are considered inoperable.
      We perform TAVR with cardiopulmonary support (CPS) for patients with low left
      ventricular (LV) function. We report two successful cases of TAVR on CPS in
      patients with low LV function and describe this technique.

PMID- 23173851
TI  - Cannabidiol (CBD) enhances lipopolysaccharide (LPS)-induced pulmonary
      inflammation in C57BL/6 mice.
AB  - Cannabidiol (CBD) is a plant-derived cannabinoid that has been predominantly
      characterized as anti-inflammatory. However, it is clear that immune effects of
      cannabinoids can vary with cannabinoid concentration, or type or magnitude of
      immune stimulus. The present studies demonstrate that oral administration of CBD
      enhanced lipopolysaccharide (LPS)-induced pulmonary inflammation in C57BL/6 mice.
      The enhanced inflammatory cell infiltrate as observed in bronchoalveolar lavage
      fluid (BALF) was comprised mainly of neutrophils, with some monocytes.
      Concomitantly, CBD enhanced pro-inflammatory cytokine mRNA production, including
      tumor necrosis factor-alpha (Tnfa), interleukins (IL)-5 and -23 (Il6, Il23), and
      granulocyte colony stimulating factor (Gcsf). These results demonstrate that the
      CBD-mediated enhancement of LPS-induced pulmonary inflammation is mediated at the
      level of transcription of a variety of pro-inflammatory genes. The significance
      of these studies is that CBD is part of a therapeutic currently in use for
      spasticity and pain in multiple sclerosis patients, and therefore it is important
      to further understand mechanisms by which CBD alters immune function. 

PMID- 23173855
TI  - Coronary sinus approach to repair an intracardiac ventricular pseudoaneurysm.
AB  - A coronary sinus approach using a Gore-Tex Patch was used to repair an
      intracardiac left ventricular pseudoaneurysm after a previous bioprosthetic
      mitral valve replacement. At follow-up six months after surgery, echocardiography
      and a computed tomographic scan revealed almost complete obliteration of the
      pseudoaneurysm cavity.

PMID- 23173856
TI  - Posterior intercostal hemorrhage following median sternotomy.
AB  - We report two cases of patients who underwent cardiac surgery and suffered from
      posterior intercostal artery bleeding. Both cases were treated by transcatheter
      arterial embolization.

PMID- 23173857
TI  - Coronary artery fistula associated with mitral valve endocarditis.
AB  - Coronary artery fistulas are rare, and the further development of mitral valvular
      insufficiency and endocarditis is even more uncommon. We report a case of
      endocarditis secondary to a congenital coronary artery fistula arising from the
      right coronary artery and draining into the left ventricle. Vegetations were
      found on the mitral valve leaflet. The fistula was successfully treated with
      surgery, and the endocarditis, with antibiotic therapy. Surgical repair is the
      optimal treatment for coronary artery fistula, even in asymptomatic patients.

PMID- 23173858
TI  - Traumatic myocardial infarction caused by shotgun bullet injury.

PMID- 23173859
TI  - Giant pericardial lipoma compressing the right atrium.

PMID- 23173860
TI  - Interatrial septal bronchogenic cyst accompanied with TAPVC.

PMID- 23173861
TI  - Successful long-term management of aneurysm-associated chronic disseminated
      intravascular coagulation with low molecular weight heparin.
AB  - Disseminated intravascular coagulation (DIC) is a well-described complication of
      aortic aneurysm. In cases where surgical repair of the aneurysm is
      contraindicated, palliative therapy via medical management of the coagulopathy
      may be warranted. We present a case of aneurysm-associated DIC successfully
      managed with low molecular weight heparin.

PMID- 23173862
TI  - Transesophageal echocardiographic guidance of percardiac device closure of
      intracardiac defects in patients weighing less than 10 kg.
AB  - BACKGROUND: To evaluate the technology of transesophageal echocardiographic
      guidance of percardiac closure in patients with low weight. METHODS: Forty-two
      patients with intracardiac defects, aged from two months to five years (median,
      18.4 months) and weighted from 4 to 10 kg (median, 8.9 kg), underwent attempted
      percardiac device closure under transesophageal echocardiographic guidance.
      RESULTS: Thirty-nine (93%) patients successfully underwent occlusion, whereas
      three patients (7.1%) were converted to conventional open-heart surgery. There
      was no mortality. They were followed up from 3 months to 15 months (median, 9.4
      months). First degree atrioventricular block was detected in one patient at the
      time of discharge. The most common electrocardiogram change was bundle-branch
      block, which developed in three (7.7%) patients during follow-up. New mild mitral
      valve regurgitation (MR) was detected in three patients after operation and
      disappeared in one but remained in two others. Pericardial perfusion and
      recurrent intubation developed in one patient, respectively. The incidence of
      late complications is 5.1% (2/39) including low cardiac output syndrome and
      residual shunt in one patient, and moderate pericardial perfusion in one patient,
      respectively. No complication such as device dislocation, thrombosis, and
      obstruction of left or right ventricular outflow tract was found during the
      follow-up. CONCLUSIONS: This initial success indicates that transesophageal
      echocardiographic guidance of percardiac device closure will aid in the treatment
      of intracardiac defects in selected patients weighing less than 10 kg with good
      early outcomes.

PMID- 23173863
TI  - Results for surgical correction of complete atrioventricular septal defect:
      associations with age, surgical era, and technique.
AB  - BACKGROUND: This study was conducted to evaluate the outcomes of patients
      undergoing complete atrioventricular septal defect (CAVSD) repair with particular
      attention to age at surgery, surgical era, and technique. METHODS: One hundred
      and forty-seven patients undergoing CAVSD repair between November 2002 and
      February 2012 were grouped according to surgical era and technique. Group I (age:
      9.4 +/- 5.0 months; weight: 6.8 +/- 1.7 kg) consisted of 45 patients, operated
      before August 2006, and was divided into subgroup Ia (31 patients; two-patch
      repair) and subgroup Ib (14 patients; modified single-patch repair). One hundred
      and two patients operated after August 2006 were included in Group II (age: 5.2
      +/- 3.1 months; weight: 4.9 +/- 2.6 kg), and was divided into subgroup IIa (59
      patients; two-patch repair) and subgroup IIb (43 patients; modified single-patch
      repair). Groups were compared with regard to perioperative variables and
      postoperative data. RESULTS: There were 19 early and five late deaths. Overall
      mortality was significantly higher in Group I, compared to Group II (p < 0.01).
      Comparison of Groups Ia to Ib and IIa to IIb revealed no statistically
      significant difference in mortality or morbidity. Age >8 months and preoperative
      common atrioventricular valve (CAVV) regurgitation >= moderate were significant
      risk factors for mortality and morbidity. After 40.8 +/- 24.4 months, 99 (80.4%)
      of 123 (83.7%) survivors were asymptomatic without any medication, and 24 (19.5%)
      have mild symptoms. CONCLUSION: Our current results indicate that younger patient
      age and better preoperative CAVV functions were the main factors for a favorable
      outcome after surgical correction of CAVSD; and outcomes did not differ by the
      surgical technique.

PMID- 23173864
TI  - Concomitant tricuspid valve repair or replacement during left ventricular assist
      device implant demonstrates comparable outcomes in the long term.
AB  - INTRODUCTION: Severe tricuspid regurgitation (TR) is present in nearly half the
      patients undergoing implant of a left ventricular assist device (LVAD) and its
      correction confers better long-term outcome. AIM: To compare the early and late
      results of tricuspid valve repair (TVrpr) or replacement (TVR) with LVAD implant.
      PATIENT AND METHODS: Sixty-four from a cohort of 126 patients had a concomitant
      tricuspid valve procedure; 48 (75%) underwent a TVrpr whereas 16 (25%) had TVR.
      All preoperative hemodynamic parameters including the mean TR grade (TVrpr; 3.6
      vs. TVR; 3.7) were comparable (p = 0.7). The mean TR grade was 1.6 +/- 1.5 for
      the remaining 62 patients who did not have a concomitant tricuspid valve
      procedure, with 4/62 (6%) having severe TR (p < 0.0001). RESULTS: Cardiopulmonary
      bypass time was longer for patients undergoing TVR (p = 0.01). There was a
      significant reduction in right atrial pressure for the entire cohort (p < 0.01)
      and the postoperative right atrial pressure was not statistically different
      between TVrpr (13.6 +/- 4.6) and TVR (11.6 +/- 4.3; p = 0.6. Postoperative
      intensive care unit stay was comparable as was the duration of inotropic support
      (p = 0.5) or need for temporary right ventricular mechanical support. In-hospital
      mortality (12%) was not different between groups. The mean time for LVAD support
      was 12.3 +/- 9.71 months and the last transthoracic echocardiographic examination
      was performed at mean intervals of 13.8 +/- 10.8 months (TVrpr) and 11.8 +/- 7.6
      months (TVR; p = 0.47). Reduction in TR grade was similar between groups (p =
      0.27). Late mortality (p = 1.00) was comparable in both groups. Using log-rank
      analysis, there was no significant difference in the estimated survival between
      TVrpr and TVR (p = 0.88). CONCLUSION: TVrpr repair at the time of LVAD implant is
      effective in correcting TR even at the end of one year of follow-up. The choice
      to repair or replace does not affect the clinical outcome.

PMID- 23173865
TI  - Salvage of permanent epicardial lead function by conversion of a bipolar to
      unipolar lead.
AB  - Increased thresholds in permanent epicardial leads pose a special challenge in
      the postoperative period. We present a case of complete heart block after
      surgical correction of a congenital heart defect that required conversion of an
      axial bipolar lead to unipolar lead to avoid lead replacement. We review the
      options for repair and describe our approach to this patient.

PMID- 23173866
TI  - Siglec-7 specifically recognizes Campylobacter jejuni strains associated with
      oculomotor weakness in Guillain-Barre syndrome and Miller Fisher syndrome.
AB  - Due to molecular mimicry, Campylobacter jejuni lipo-oligosaccharides can induce a
      cross-reactive antibody response to nerve gangliosides, which leads to Guillain
      Barre syndrome (GBS). Cross-reactive antibodies to ganglioside GQ1b are strongly
      associated with oculomotor weakness in GBS and its variant, Miller Fisher
      syndrome (MFS). Antigen recognition is a crucial first step in the induction of a
      cross-reactive antibody response, and it has been shown that GQ1b-like epitopes
      expressed on the surface of C. jejuni are recognized by sialic acid-binding
      immunoglobulin-like lectin-7 (Siglec-7). We aimed to determine the epitope
      specificity of C. jejuni binding to Siglec-7, and correlate the outcome to
      disease symptoms in GBS and MFS patients. Using a well-defined GBS/MFS-associated
      C. jejuni strain collection, which included three sialic acid knockout strains,
      we found that Siglec-7 exclusively binds to C. jejuni strains that express
      terminal disialylated ganglioside mimics. When serological and diagnostic patient
      records were correlated with the Siglec-7-binding properties, we observed an
      association between Siglec-7 binding and the presence of anti-GQ1b antibodies in
      patient serum. In addition, Siglec-7 binding was associated with oculomotor
      weakness in GBS and MFS patients. Lipo-oligosaccharide-specific binding of C.
      jejuni to Siglec-7 may be an initiating event in immune recognition and
      presentation, and lead to anti-GQ1b antibody production and the development of
      ocular weakness in GBS or MFS.

PMID- 23173868
TI  - Rumination variations: aetiology and classification of abnormal behavioural
      responses to digestive symptoms based on high-resolution manometry studies.
AB  - BACKGROUND: Rumination is the voluntary, albeit subconscious return of gastric
      contents to the mouth. Currently, rumination syndrome and repetitive belching
      disorders are considered separate diagnoses, as defined by Rome III criteria and
      high-resolution oesophageal manometry (HRM). AIM: To test the hypothesis that
      these conditions represent a common behavioural response to aversive digestive
      stimuli and that successful treatment can be directed at both the stimulus and
      the response. METHODS: Case-note review of consecutive patients with a final
      diagnosis of behavioural digestive disorders between August 2009 and October
      2011. RESULTS: Thirty-five of 46 (76%) patients exhibited 'classical' rumination
      with abdomino-gastric strain (R-waves) driving gastric contents across the lower
      oesophageal sphincter; 5 (11%) had 'reflux-related' rumination with R-waves seen
      during gastro-oesophageal common cavity (reflux) events and 6 had (13%) supra
      gastric belching. All received at least one biofeedback session at the time of
      diagnosis with a good response reported by 20/46 (43%) of the patients, which
      included 3 with supra-gastric belching. Additionally, rumination ceased in cases
      in which definitive treatment relieved the symptoms that triggered abnormal
      behaviour (e.g. fundoplication in 'reflux-rumination'). CONCLUSIONS: Rumination
      and many of its variations, excluding only some cases of supra-gastric belching,
      are associated with abdomino-gastric strain, a generic abnormal behavioural
      response to a variety of aversive digestive stimuli. All types of rumination can
      respond to biofeedback. High-resolution oesophageal manometry identifies
      subgroups with distinct mechanisms of disease that respond to specific management
      targeted at the symptoms that trigger the abnormal behaviour.

PMID- 23173867
TI  - Experimental determination of the oral bioavailability and bioaccessibility of
      lead particles.
AB  - In vivo estimations of Pb particle bioavailability are costly and variable,
      because of the nature of animal assays. The most feasible alternative for
      increasing the number of investigations carried out on Pb particle
      bioavailability is in vitro testing. This testing method requires calibration
      using in vivo data on an adapted animal model, so that the results will be valid
      for childhood exposure assessment. Also, the test results must be reproducible
      within and between laboratories. The Relative Bioaccessibility Leaching
      Procedure, which is calibrated with in vivo data on soils, presents the highest
      degree of validation and simplicity. This method could be applied to Pb
      particles, including those in paint and dust, and those in drinking water
      systems, which although relevant, have been poorly investigated up to now for
      childhood exposure assessment.

PMID- 23173869
TI  - Subjective well-being in times of social change: congruence of control strategies
      and perceived control.
AB  - This paper investigates the association between perceptions of broader changes in
      the social-ecological context and individuals' subjective well-being (SWB). Macro
      level societal changes such as globalization or demographic change give rise to
      new demands for individual functioning at work and/or in the family. Such new
      demands associated with social change are stressful and likely to be related to
      lower levels of SWB. Being active agents, individuals attempt to deal with social
      change and its increasing demands to protect their SWB. The present study
      investigates which kinds of control strategies are most effective in protecting
      one's SWB. Specifically, we predicted that control strategies of goal engagement
      will be most effective under conditions of perceived high control, and control
      strategies of goal disengagement will be most effective under conditions of
      perceived low control. In a large sample of 2537 German adults, work- and family
      related demands associated with social change were found to be negatively linked
      to SWB. Moreover and in line with the motivational theory of lifespan
      development, control strategies of goal engagement and disengagement were
      beneficial for SWB to the extent that they matched the perceived control of the
      demands associated with social change. 

PMID- 23173870
TI  - Reduced expression of microRNA-100 confers unfavorable prognosis in patients with
      bladder cancer.
AB  - OBJECTIVE: MicroRNA-100 (miR-100) has been demonstrated to be downregulated in
      bladder cancer tissues, and enforced expression of this miRNA may inhibit cell
      growth and colony formation of human bladder cancer 5637 cells in vitro. However,
      the clinical significance of miR-100 in human bladder cancer has not yet been
      elucidated. Thus, the aim of this study was to investigate the diagnostic and
      prognostic values of miR-100 in this disease. METHODS: Expression levels of miR
      100 in 126 pairs of bladder cancer and adjacent normal tissues were detected by
      TaqMan real-time quantitative RT-PCR assay. In order to determine its prognostic
      value, overall survival (OS) and progression-free survival (PFS) were evaluated
      using the Kaplan-Meier method, and multivariate analysis was performed using the
      Cox proportional hazard analysis. RESULTS: Expression levels of miR-100 in
      bladder cancer tissues were significantly lower than those in adjacent normal
      tissues (mean expression level: 2.6 +/- 1.2 vs. 3.9 +/- 1.5, P < 0.001). When
      categorized into low vs. high expression, low miR-100 expression was negatively
      associated with the stage (P = 0.01), the recurrence (P = 0.008), the progression
      (P = 0.01), and the death (P < 0.001) of patients with bladder cancer. Moreover,
      low miR-100 expression clearly predicted poorer PFS (P = 0.001) and OS (P <
      0.001). In the multivariate analysis, low miR-100 expression was an independent
      prognostic factor for both PFS (P = 0.01) and OS (P = 0.008). CONCLUSION: Our
      data offer the convincing evidence that miR-100 may play an important role in the
      progression of bladder cancer and that the reduced expression of this miRNA may
      be independently associated with shorter PFS and OS of patients, suggesting that
      miR-100 might be a potential marker for further risk stratification in the
      treatment of this cancer. VIRTUAL SLIDES: The virtual slides' for this article
      can be found here:
      http://www.diagnosticpathology.diagnomx.eu/vs/1105483419841671.

PMID- 23173871
TI  - Evaluation of function predictions by PFP, ESG,and PSI-BLAST for moonlighting
      proteins.
AB  - BACKGROUND: Advancements in function prediction algorithms are enabling large
      scale computational annotation for newly sequenced genomes. With the increase in
      the number of functionally well characterized proteins it has been observed that
      there are many proteins involved in more than one function. These proteins
      characterized as moonlighting proteins show varied functional behavior depending
      on the cell type, localization in the cell, oligomerization, multiple binding
      sites, etc. The functional diversity shown by moonlighting proteins may have
      significant impact on the traditional sequence based function prediction methods.
      Here we investigate how well diverse functions of moonlighting proteins can be
      predicted by some existing function prediction methods. RESULTS: We have analyzed
      the performances of three major sequence based function prediction methods,PSI
      BLAST, the Protein Function Prediction (PFP), and the Extended Similarity Group
      (ESG) on predicting diverse functions of moonlighting proteins. In predicting
      discrete functions of a set of 19 experimentally identified moonlighting
      proteins, PFP showed overall highest recall among the three methods. Although ESG
      showed the highest precision, its recall was lower than PSI-BLAST. Recall by PSI
      BLAST greatly improved when BLOSUM45 was used instead of BLOSUM62. CONCLUSION: We
      have analyzed the performances of PFP, ESG, and PSI-BLAST in predicting the
      functional diversity of moonlighting proteins. PFP shows overall better
      performance in predicting diverse moonlighting functions as compared with PSI
      BLAST and ESG. Recall by PSI-BLAST greatly improved when BLOSUM45 was used. This
      analysis indicates that considering weakly similar sequences in prediction
      enhances the performance of sequence based AFP methods in predicting functional
      diversity of moonlighting proteins. The current study will also motivate
      development of novel computational frameworks for automatic identification of
      such proteins.

PMID- 23173872
TI  - Prevalence of beta-lactamase-producing bacteria in human periodontitis.
AB  - BACKGROUND AND OBJECTIVE: Beta-lactam antibiotics prescribed in periodontal
      therapy are vulnerable to degradation by bacterial beta-lactamases. This study
      evaluated the occurrence of beta-lactamase-positive subgingival bacteria in
      chronic periodontitis subjects of USA origin, and assessed their in vitro
      resistance to metronidazole at a breakpoint concentration of 4 MUg/mL. MATERIAL
      AND METHODS: Subgingival plaque specimens from deep periodontal pockets with
      bleeding on probing were removed from 564 adults with severe chronic
      periodontitis before treatment. The samples were transported in VMGA III and then
      plated onto: (i) nonselective enriched Brucella blood agar (EBBA) and incubated
      anaerobically for 7 d; and (ii) selective trypticase soy-bacitracin-vancomycin
      (TSBV) and incubated for 3 d in air + 5% CO2 . At the end of the incubation
      periods, the bacterial test species were identified and quantified. Specimen
      dilutions were also plated onto EBBA plates supplemented with 2 MUg/mL of
      amoxicillin, a combination of 2 MUg/mL of amoxicillin plus 2 MUg/mL of the beta
      lactamase inhibitor clavulanic acid, or 4 MUg/mL of metronidazole, followed by
      anaerobic incubation for 7 d. Bacterial test species presumptively positive for
      beta-lactamase production were identified by growth on EBBA primary isolation
      plates supplemented with amoxicillin alone and no growth on EBBA primary
      isolation plates containing both amoxicillin plus clavulanic acid. A subset of
      such isolates was subjected to nitrocefin-based chromogenic disk testing to
      confirm the presence of beta-lactamase activity. In vitro resistance to 4 MUg/mL
      of metronidazole was noted when growth of test species occurred on metronidazole
      supplemented EBBA culture plates. RESULTS: Two-hundred and ninety-four (52.1%) of
      the study subjects yielded beta-lactamase-producing subgingival bacterial test
      species, with Prevotella intermedia/nigrescens, Fusobacterium nucleatum and other
      Prevotella species most frequently identified as beta-lactamase-producing
      organisms. Of the beta-lactamase-producing bacterial test species strains
      recovered, 98.9% were susceptible in vitro to metronidazole at 4 MUg/mL.
      CONCLUSION: The occurrence of beta-lactamase-positive subgingival bacterial
      species in more than half of the subjects with severe chronic periodontitis
      raises questions about the therapeutic potential of single-drug regimens with
      beta-lactam antibiotics in periodontal therapy. The in vitro effectiveness of
      metronidazole against nearly all recovered beta-lactamase-producing subgingival
      bacterial species further supports clinical periodontitis treatment strategies
      involving the combination of systemic amoxicillin plus metronidazole.

PMID- 23173873
TI  - A multiscale and multiparametric approach for modeling the progression of oral
      cancer.
AB  - BACKGROUND: In this work, we propose a multilevel and multiparametric approach in
      order to model the growth and progression of oral squamous cell carcinoma (OSCC)
      after remission. OSCC constitutes the major neoplasm of the head and neck region,
      exhibiting a quite aggressive nature, often leading to unfavorable prognosis.
      METHODS: We formulate a Decision Support System assembling a multitude of
      heterogeneous data sources (clinical, imaging tissue and blood genomic), aiming
      to capture all manifestations of the disease. Our primary aim is to identify the
      factors that dictate OSCC progression and subsequently predict potential relapses
      of the disease. The discrimination potential of each source of data is initially
      explored separately, and afterwards the individual predictions are combined to
      yield a consensus decision achieving complete discrimination between patients
      with and without a disease relapse. Moreover, we collect and analyze gene
      expression data from circulating blood cells throughout the follow-up period in
      consecutive time-slices, in order to model the temporal dimension of the disease.
      For this purpose a Dynamic Bayesian Network (DBN) is employed which is able to
      capture in a transparent manner the underlying mechanism dictating the disease
      evolvement, and employ it for monitoring the status and prognosis of the patients
      after remission. RESULTS: By feeding as input to the DBN data from the baseline
      visit we achieve accuracy of 86%, which is further improved to complete
      discrimination when data from the first follow-up visit are also employed.
      CONCLUSIONS: Knowing in advance the progression of the disease, i.e. identifying
      groups of patients with higher/lower risk of reoccurrence, we are able to
      determine the subsequent treatment protocol in a more personalized manner.

PMID- 23173874
TI  - Use of statins in lower extremity artery disease: a review.
AB  - BACKGROUND: Lower extremity artery disease (LE-PAD) is one of the most common
      manifestations of atherosclerosis, particularly in elderly patients, and it is
      related to a high cardiovascular risk. DESCRIPTION: It is well established that
      statin therapy is characterized by crucial benefits on cardiovascular system by
      limiting atherosclerotic progression and reducing cardiovascular events and
      mortality. A growing body of evidence support efficacy of statins in LE-PAD due
      to the ability of both reducing cardiovascular risk and improving walking
      distance and, hence, quality of life. Consequently, statin therapy should be
      considered in all LE-PAD patients and new LDL-cholesterol targets should be
      reached. CONCLUSIONS: Our opinion is that statin therapy remains still
      underutilized or with inadequate dosage, so therapy of LE-PAD patients should be
      improved to obtain all the demonstrated benefits of statins.

PMID- 23173875
TI  - A dedicated surveillance network for congenital toxoplasmosis in Greece, 2006
      2009: assessment of the results.
AB  - BACKGROUND: Toxoplasmosis is caused by infection with the protozoan parasite
      Toxoplasma gondii. Acute infections in pregnant women may be transmitted to the
      fetus and cause severe illness. The purpose of this study was to establish a
      dedicated surveillance network (DSN) for congenital toxoplasmosis (CT) in Greece,
      in order to assess the birth prevalence of CT. METHODS: A DSN of thirty
      clinicians was established for reporting CT cases from hospitals throughout
      Greece. The clinicians were selected on the basis that there was a high
      possibility the suspected cases would be referred to them from district hospitals
      or private clinics. Suspected cases of CT were reported on a monthly basis with a
      zero reporting card during a surveillance period from April 2006 to December
      2009. A questionnaire was sent for any suspected case to record information
      including demographic parameters, clinical signs and symptoms and laboratory
      results. Serological and molecular confirmation of cases was performed by the
      Pasteur Hellenic Institute. All newborns suspected of CT received treatment and
      were serologically and clinically followed up for one year. RESULTS: The monthly
      response rate reached 100%, although only after reminders sent to 65% of the
      participant physicians. Sixty-three suspected CT cases were recorded by the DSN
      during the study period including fourteen confirmed and seven probable cases.
      Ten cases (47.6%) presented with symptoms at birth. Chorioretinitis was the most
      prominent manifestation, occurring in five symptomatic CT cases (50%). No other
      symptoms appeared by the end of the one year clinical follow up. No case was
      recorded by the existing surveillance system of the Hellenic Center of Disease
      Control and Prevention (HCDCP) during the same time period. Birth prevalence was
      estimated at 0.45, 0.51 and 0.51 per 10,000 births for 2007, 2008 and 2009
      respectively. The incidence rate of symptomatic CT at birth was estimated at 0.10
      cases per 10,000 births per year in Greece (for the period 2007-2009).
      CONCLUSION: The DSN for CT proved to be more sensitive than the classical
      notification system, easy in application and very efficient in reporting rare
      diseases such as CT. Similar DSNs could be used to provide useful information on
      other rare diseases.

PMID- 23173876
TI  - Hormonal response during physical exercise of different intensities in
      adolescents with type 1 diabetes and healthy controls.
AB  - BACKGROUND: Physical activity is a critical component in the care of diabetes.
      Although it offers health benefits it presents challenges. OBJECTIVE: To
      investigate differences between adolescent boys and girls with type 1 diabetes
      and healthy controls in terms of maximal work capacity (VO(2)  max) and hormonal
      response to physical exercise of different intensities. SUBJECTS: Twelve
      individuals (six boys and six girls; age 14-19 yr, pubertal stage 4-5) with type
      1 diabetes (duration, 6.3 +/- 4.4 yr; hemoglobin A1c, 63 +/- 10 mmol/mol) were
      compared with 12 healthy controls matched for age, sex, pubertal stage, body mass
      index standard deviation score, and amount of regular physical activity. METHODS:
      During consecutive days, three different workloads; maximal, endurance, and
      interval, were performed on an Ergometer cycle. During the tests, levels of
      lactate, glucose, insulin, and regulatory hormones [glucagon, cortisol, growth
      hormone (GH), adrenaline, and noradrenaline] were measured in blood. Subcutaneous
      glucose was measured continuously. RESULTS: VO(2)  max did not differ between the
      groups, diabetes 49.8 +/- 9.9 vs. control 50.7 +/- 12.0 mL/min/kg. Hormonal
      responses did not differ between the groups except for mean peak GH level during
      the interval test, diabetes 63.2 +/- 27.0 vs. control 33.8 +/- 20.9 mU/L, p <
      0.05. CONCLUSIONS: Physical capacity and hormonal regulation of blood glucose in
      connection with physical exercise of different intensities did not differ between
      adolescents with diabetes and healthy controls. Thus, adolescents with type 1
      diabetes can participate in physical activity on the same terms as healthy peers.

PMID- 23173877
TI  - Assessing diabetes-related quality of life of youth with type 1 diabetes in
      routine clinical care: the MIND Youth Questionnaire (MY-Q).
AB  - AIM: It is recommended to assess health-related quality of life (HRQoL) in
      teenagers with diabetes as part of their ongoing medical care. Here, we describe
      the development and psychometric evaluation of the Monitoring Individual Needs in
      Diabetes Youth Questionnaire (MY-Q), a multi-dimensional self-report HRQoL
      questionnaire designed for use in pediatric diabetes care. DESIGN AND METHODS: In
      expert meetings, characteristics and domains of interest were defined. Existing
      questionnaires were reviewed, topics selected, and new items added, resulting in
      the 36-item MY-Q. To test face validity, we interviewed 22 teenagers. In
      addition, 84 teenagers with type 1 diabetes (age 10-18 yr) completed the MY-Q and
      Pediatric Quality of Life Inventory (PedsQL) generic and diabetes-modules to
      examine psychometric properties. Hemoglobin A1c (HbA1c) values were obtained by
      chart audit. RESULTS: The MY-Q consists of seven subscales (social impact,
      parents, diabetes control perceptions, responsibility, worries, treatment
      satisfaction, and body image and eating behavior) as well as general HRQoL and
      emotional well-being. Cronbach's alpha for the total scale was 0.80. Strong
      correlations between MY-Q total and PedsQL generic and diabetes-module scores (r
      = 0.58 and r = 0.71, p < 0.001) confirmed concurrent validity. Higher HbA1c was
      associated with lower diabetes control perceptions (r = -0.35, p = 0.001),
      worries (r = -0.24, p = 0.029), and body image and eating behavior (r = -0.26, p
      = 0.019) scores. Younger age was associated with higher diabetes control
      perceptions (r = -0.26, p = 0.020) and body image and eating behavior (r = -0.23,
      p = .038), and lower responsibility (r = 0.25, p = 0.027) scores. CONCLUSION: The
      MY-Q is the first HRQoL questionnaire designed for use in clinical care. It has
      acceptable measurement properties and seems suitable for implementation in
      routine care of teenagers with diabetes.

PMID- 23173878
TI  - Impact of physicians' sex on treatment choices for low back pain.
AB  - BACKGROUND: Little information is available regarding physicians' sex as a
      potential bias in making pain treatment decisions. This study investigated how
      sex of the medical care provider and patient characteristics influence choices
      that are made in the treatment of low back pain. METHODS: Data of 186 charts of
      patients with low back pain (46% males) who were seen by trained residents were
      analyzed in this retrospective observational study. The primary outcome was the
      first treatment choice that was made, which was categorized in three groups:
      pharmacological therapy; invasive procedures; or other options at the time of
      first consultation. Chi-square statistics and multinominal logistic regression
      analysis were used to examine associations between physicians' and/or patients'
      sex and treatment choices. RESULTS: Physicians' sex was found to be a significant
      predictor of the first decision that was made in the treatment of low back pain.
      Female physicians tended to prescribe more pharmacological agents as their first
      treatment choice. No significant sex differences were found for invasive
      therapies or other treatment options as a first choice. These findings were found
      to be independent from previous received pain therapies before consultation by
      the specialized pain clinician. Further, patients' sex did not influence
      decisions on pain management nor did gender concordance or discordance in the
      patient-physician relationship. CONCLUSIONS: Physicians' sex had a significant
      impact on pain management decisions in patients with low back pain. Female
      physicians prescribed more pharmacological agents as their first choice compared
      to male physicians.

PMID- 23173879
TI  - Prevalence of negative life events and chronic adversities in European pre- and
      primary-school children: results from the IDEFICS study.
AB  - BACKGROUND: Children are not always recognized as being susceptible to stress,
      although childhood stressors may originate from multiple events in their everyday
      surroundings with negative effects on children's health. METHODS: As there is a
      lack of large-scale, European prevalence data on childhood adversities, this
      study presents the prevalence of (1) negative life events and (2) familial and
      social adversities in 4637 European pre- and primary-school children (4-11 years
      old), using a parentally-reported questionnaire embedded in the IDEFICS project
      ('Identification and prevention of Dietary- and lifestyle-induced health EFfects
      In Children and infantS'). RESULTS: The following findings were observed: (1)
      Certain adversities occur only rarely, while others are very regular (i.e.
      parental divorce); (2) A large percentage of children is shielded from stressors,
      while a small group of children is exposed to multiple, accumulating adversities;
      (3) The prevalence of childhood adversity is influenced by geographical location
      (e.g. north versus south), age group and sex; (4) Childhood adversities are
      associated and co-occur, resulting in potential cumulative childhood stress.
      CONCLUSIONS: This study demonstrated the importance of not only studying
      traumatic events but also of focusing on the early familial and social
      environment in childhood stress research and indicated the importance of
      recording or monitoring childhood adversities.

PMID- 23173880
TI  - Vocal fold vibration amplitude, open quotient, speed quotient and their
      variability along glottal length: kymographic data from normal subjects.
AB  - Abstract Quantitative knowledge about healthy vocal fold vibration
      characteristics provides the basis for an objective assessment of vocal fold
      vibrations. In this study, using high-speed videolaryngoscopy the alterations of
      the relative vibration amplitudes, open quotients, and speed quotients were
      analyzed along the glottal length in 30 male and 30 female healthy subjects. The
      maximum vibration amplitude was identified at 41.1% +/- 10.8% and 46.5% +/- 18.0%
      of the visible glottal length in females and males, respectively. The average
      open quotients decreased in females and males from posterior to anterior, while
      the speed quotients did not change systematically. The reported normative values
      can be used to distinguish normal and abnormal vibrations in clinical practice
      when aiming at quantitative diagnosis of functional voice disorders. 

PMID- 23173881
TI  - Chemical differentiation of two taste variants of Gynostemma pentaphyllum by
      using UPLC-Q-TOF-MS and HPLC-ELSD.
AB  - To differentiate the sweet and bitter taste variants of a Chinese medicinal tea
      Gynostemma pentaphyllum (GP), a method for the quantitative analysis of
      ginsenosides Rb(1), Rb(3), Rd, and F(2) in GP by using UPLC-Q-TOF-MS was
      developed. According to the different contents of the four ginsenosides, chemical
      differentiation of the two taste variants of GP was achieved by principal
      component analysis (PCA). A supplementary quantitative analysis method of using
      HPLC-ELSD for determination of 20(S)-panaxadiol in the hydrolysates of GP was
      also developed. Similarly, chemical differentiation based on different amounts of
      20(S)-panaxadiol was established and the result was well consistent with that
      based on the analysis of the four ginsenosides. It was found that the amounts of
      the four ginsenosides and 20(S)-panaxadiol in the sweet taste variant were
      significantly higher than those in the bitter one. The significant difference
      between the sweet and bitter taste variants of GP was easily visualized in 3D-PCA
      score plots. The PCA loading plot also indicated the contributions among the four
      ginsenosides (Rd > Rb(3) > F(2) > Rb(1)) for distinguishing the two taste
      variants. This is the first report to describe the use of these two quantitative
      methods (UPLC-Q-TOF-MS and HPLC-ELSD) for the accurate authentication and quality
      control of GP.

PMID- 23173882
TI  - Early outcomes of colon laparoscopic resection in the elderly patients compared
      with the younger.
AB  - BACKGROUND: The aim of this study was to define any benefits in terms of early
      outcome for laparoscopic colectomy in patients over 75 years old (OP) compared
      with the outcomes of a younger populations (YP). METHODS: Forty elderly patients
      undergoing laparoscopic colectomy for colorectal cancer between 2007-2011 were
      studied, the patients are divided for gender, age, year of surgery, site of
      cancer, and comorbidity on admission and compared with 40 younger patients.
      RESULTS AND DISCUSSION: Mean (standard deviation) age was 81.3 in OP and 68.3 YP
      Conversion rate was the same between the two groups. There was no difference in
      operative mean time . The overall mortality rate was 0% percent. The surgical
      morbidity rate was the same but there was an increased in cardiologic e
      bronchopneumonia complications in older population. Patients treated with
      laparoscopic approach had a faster recovery of bowel function and a significant
      reduction of the mean length of hospital stay not age related. Laparoscopy
      allowed a better preservation of postoperative independence status. CONCLUSIONS:
      Laparoscopic colectomy for cancer in elderly patients is safe and beneficial
      including preservation of postoperative independence and a reduction of length of
      hospital stay.

PMID- 23173883
TI  - Surgery for a gastric Dieulafoy's lesion reveals an occult bleeding jejunal
      diverticulum. A case report.
AB  - BACKGROUND: Jejunal diverticulosis is an uncommon disease and usually
      asymptomatic. It can be complicated not only by diverticulitis, but by
      hemorrhage, perforation, intussusception, volvulus, malabsorption and even small
      bowel obstruction due to enteroliths formed and expelled from these diverticula.
      METHODS: We describe a case of an occult bleeding jejunal diverticulum, casually
      discovered in a patient that was taken to surgery for a Dieulafoy's lesion after
      unsuccessful endoscopic treatment. We performed a gastric resection together with
      an ileocecal resection.Macroscopic and microscopic examinations confirmed the
      gastric Dieulafoy's lesion and demonstrated the presence of another source of
      occult bleeding in asymptomatic jejunal diverticulum. DISCUSSION: The current
      case emphasizes that some gastrointestinal bleeding lesions, although rare, can
      be multiple and result in potentially life-threatening bleeding. The clinician
      must be mindful to the possibility of multisite lesions and to the correlation
      between results of the investigations and clinical condition of the bleeding
      patient.

PMID- 23173884
TI  - Assessment of inter-examiner agreement and variability in the manual
      classification of auditory brainstem response.
AB  - BACKGROUND: The analysis of the Auditory Brainstem Response (ABR) is of
      fundamental importance to the investigation of the auditory system behaviour,
      though its interpretation has a subjective nature because of the manual process
      employed in its study and the clinical experience required for its analysis. When
      analysing the ABR, clinicians are often interested in the identification of ABR
      signal components referred to as Jewett waves. In particular, the detection and
      study of the time when these waves occur (i.e., the wave latency) is a practical
      tool for the diagnosis of disorders affecting the auditory system. Significant
      differences in inter-examiner results may lead to completely distinct clinical
      interpretations of the state of the auditory system. In this context, the aim of
      this research was to evaluate the inter-examiner agreement and variability in the
      manual classification of ABR. METHODS: A total of 160 ABR data samples were
      collected, for four different stimulus intensity (80dBHL, 60dBHL, 40dBHL and
      20dBHL), from 10 normal-hearing subjects (5 men and 5 women, from 20 to 52
      years). Four examiners with expertise in the manual classification of ABR
      components participated in the study. The Bland-Altman statistical method was
      employed for the assessment of inter-examiner agreement and variability. The
      mean, standard deviation and error for the bias, which is the difference between
      examiners' annotations, were estimated for each pair of examiners. Scatter plots
      and histograms were employed for data visualization and analysis. RESULTS: In
      most comparisons the differences between examiner's annotations were below 0.1
      ms, which is clinically acceptable. In four cases, it was found a large error and
      standard deviation (>0.1 ms) that indicate the presence of outliers and thus,
      discrepancies between examiners. CONCLUSIONS: Our results quantify the inter
      examiner agreement and variability of the manual analysis of ABR data, and they
      also allows for the determination of different patterns of manual ABR analysis.

PMID- 23173885
TI  - Comparative studies of Al-doped ZnO and Ga-doped ZnO transparent conducting oxide
      thin films.
AB  - We have investigated the influences of aluminum and gallium dopants (0 to 2.0
      mol%) on zinc oxide (ZnO) thin films regarding crystallization and electrical and
      optical properties for application in transparent conducting oxide devices. Al-
      and Ga-doped ZnO thin films were deposited on glass substrates (corning 1737) by
      sol-gel spin-coating process. As a starting material, AlCl3?6H2O, Ga(NO3)2, and
      Zn(CH3COO)2?2H2O were used. A lowest sheet resistance of 3.3 * 103 Omega/? was
      obtained for the GZO thin film doped with 1.5 mol% of Ga after post-annealing at
      650 degrees C for 60 min in air. All the films showed more than 85% transparency
      in the visible region. We have studied the structural and microstructural
      properties as a function of Al and Ga concentrations through X-ray diffraction
      and scanning electron microscopy analysis. In addition, the optical bandgap and
      photoluminescence were estimated.

PMID- 23173886
TI  - Relationship between circumcision scar thickness, postcircumcision mucosal cuff
      length measures and premature ejaculation.
AB  - OBJECTIVE: The etiology of premature ejaculation (PE) is unknown. Over the past
      two decades several studies have suggested that lifelong and acquired PE may be
      caused by somatic disorders and/or neurobiological disturbances. One
      controversial factor is the effect of circumcision on ejaculation. This
      prospective study investigated the relationship between postcircumcision penile
      mucosal cuff length, circumcision scar thickness and the PE syndromes. Features
      of PE patients were compared with those of a normal healthy control (NHC) group.
      MATERIAL AND METHODS: In total, 160 circumcised men were studied: 80 men with PE
      and 80 men in the NHC group. The following data and measurements were evaluated:
      age, type of PE syndrome, intravaginal ejaculation latency time (IELT),
      circumcision scar thickness and postcircumcision mucosal cuff length. RESULTS: In
      terms of the mean IELT, a statistically significant difference was detected
      between the PE syndromes (p < 0.05), and between the PE patients and the control
      group (p < 0.05). Among the four PE syndromes, there was no significant
      difference related to the mean mucosal cuff length and mean circumcision scar
      thickness (p > 0.05). No significant difference was observed between the two
      groups for mean mucosal cuff length (p > 0.05) or mean circumcision scar
      thickness (p > 0.05). CONCLUSION: In this study, no relationship was observed
      between PE and postcircumcision penile mucosal cuff length and circumcision scar
      thickness. Further studies are required to evaluate the positive and negative
      effects of circumcision on PE syndromes.

PMID- 23173888
TI  - Living longer: our challenges in geriatric ESRD. Introduction.

PMID- 23173889
TI  - The older patient with end-stage renal disease: is chronic dialysis the best
      option?
AB  - The mean age of the ESRD population continues to increase, with the 2011 USRDS
      Annual Data report noting it to be 62.6 years among a prevalent chronic dialysis
      population (both hemo- and peritoneal dialyses) of approximately 399,000. As with
      previous reports, the greatest growth rate per million population in the ESRD
      cohort occurs in age range >75 years. Entering the ESRD pool >75 years of age are
      about 5,000 patients/million population; in contrast, the number is about
      2,100/million population that falls in the age range 45-65 years. Baseline
      comorbid conditions, especially complications associated with diabetes and
      cardiovascular disease (CVD), accelerate with duration of ESRD, and compound the
      already high morbidity and mortality. With aging comes progressive vascular
      disease, making it more likely that the elderly will have a central venous
      catheter (CVC) access, rather than a fistula, for starting and continuing
      dialysis, hence, increased hospitalization and death rates associated with access
      clotting and infection (sepsis). The scenario in the elderly patient on dialysis
      is often a poor quality of life with repeated hospitalizations and eventual
      nursing home placement. For those patients who survive such a disabled state
      leads to the question whether chronic dialysis therapy is the best option. Our
      goal as committed nephrologists is to deliver compassionate, quality care. In the
      sick, older patient let us rethink what is the best option as they enter ESRD.

PMID- 23173887
TI  - Who should be prioritized for renal transplantation?: Analysis of key stakeholder
      preferences using discrete choice experiments.
AB  - BACKGROUND: Policies for allocating deceased donor kidneys have recently shifted
      from allocation based on Human Leucocyte Antigen (HLA) tissue matching in the UK
      and USA. Newer allocation algorithms incorporate waiting time as a primary
      factor, and in the UK, young adults are also favoured. However, there is little
      contemporary UK research on the views of stakeholders in the transplant process
      to inform future allocation policy. This research project aimed to address this
      issue. METHODS: Discrete Choice Experiment (DCE) questionnaires were used to
      establish priorities for kidney transplantation among different stakeholder
      groups in the UK. Questionnaires were targeted at patients, carers, donors /
      relatives of deceased donors, and healthcare professionals. Attributes considered
      included: waiting time; donor-recipient HLA match; whether a recipient had
      dependents; diseases affecting life expectancy; and diseases affecting quality of
      life. RESULTS: Responses were obtained from 908 patients (including 98 ethnic
      minorities); 41 carers; 48 donors / relatives of deceased donors; and 113
      healthcare professionals. The patient group demonstrated statistically different
      preferences for every attribute (i.e. significantly different from zero) so
      implying that changes in given attributes affected preferences, except when
      prioritizing those with no rather than moderate diseases affecting quality of
      life. The attributes valued highly related to waiting time, tissue match,
      prioritizing those with dependents, and prioritizing those with moderate rather
      than severe diseases affecting life expectancy. Some preferences differed between
      healthcare professionals and patients, and ethnic minority and non-ethnic
      minority patients. Only non-ethnic minority patients and healthcare professionals
      clearly prioritized those with better tissue matches. CONCLUSIONS: Our
      econometric results are broadly supportive of the 2006 shift in UK transplant
      policy which emphasized prioritizing the young and long waiters. However, our
      findings suggest the need for a further review in the light of observed
      differences in preferences amongst ethnic minorities, and also because those with
      dependents may be a further priority.

PMID- 23173890
TI  - Geriatric assessment for the nephrologist.
AB  - Dialysis providers are increasingly being presented with progressively older and
      frailer patients, in all healthcare settings from the acute hospital to the
      community dialysis center. These patients commonly bring more than kidney failure
      with them, with a complex constellation of chronic illness, comorbidity, and
      functional and cognitive impairment. Navigating these challenges and coordinating
      the care of these highly complex patients significantly increase the work of the
      whole dialysis team. This article reviews the role of Comprehensive Geriatric
      Assessment in these patients and discusses how each of its elements interacts
      with routine dialysis care.

PMID- 23173891
TI  - Predialyis nephrology care of older individuals approaching end-stage renal
      disease.
AB  - Many older patients with advanced CKD approaching ESRD do not receive timely
      nephrology care, although data suggest that the situation may be improving. In
      2005-2008, 43% of older patients who initiated renal replacement therapy had
      experienced an outpatient nephrologist consultation more than 1 year before
      starting treatment. Earlier consultation with a nephrologist has been found to
      provide better access to peritoneal dialysis and kidney transplantation, better
      preparation for the chosen dialytic modality, and improved survival after start
      of dialysis or receipt of a kidney transplant. Recent data suggest that older
      individuals are less likely to receive treatment for ESRD compared with younger
      individuals in whom almost all receive dialysis treatment or transplantation.
      Little is known about the role nephrologists play in the decision whether to
      initiate dialysis or choose a conservative route among older adults with ESRD.
      Defining the appropriate role and involvement of nephrologists in the decision
      about initiating renal replacement therapy in older adults seems ripe for further
      investigation and discussion.

PMID- 23173893
TI  - Advance care planning in patients with chronic kidney disease.
AB  - Poor communication and failure to establish goals of care result in unnecessary
      admissions to hospital, invasive procedures, suffering, and prolongation of the
      dying process for many CKD patients. Comprehensive CKD care requires systematic
      integration of advance care planning (ACP). This report describes an approach to
      ACP for patients with CKD, discusses essential aspects of how to facilitate these
      conversations, and briefly reviews the empirical evidence supporting the value of
      ACP.

PMID- 23173892
TI  - Optimal hemodialysis vascular access in the elderly patient.
AB  - The optimal vascular access for elderly patients remains a challenge due to the
      difficulty balancing the benefits and risks in a population with increased
      comorbidity and decreased survival. Age is commonly associated with failure to
      mature in fistula and decreased rates of primary and secondary patency in both
      fistula and grafts. In the elderly, at 1 and 2 years, primary patency rates range
      from 43% to 74% and from 29% to 67%, respectively. Secondary patency rates at 1
      and 2 years range from 56% to 82% and 44% to 67%, respectively. Cumulative
      fistula survival is no better than grafts survival when primary failures are
      included. Several observational studies consistently demonstrate a lower adjusted
      mortality among those using a fistula compared with a catheter; however, catheter
      use in the elderly is increasing in most countries with the exception of Japan.
      Both guidelines and quality initiatives do not acknowledge the trade-offs
      involved in managing the elderly patients with multiple chronic conditions and
      limited life expectancy or the value that patients place on achieving these
      outcomes. The framework for choice of vascular access presented in this article
      considers: (1) likelihood of disease progression before death, (2) patient life
      expectancy, (3) risks and benefits by vascular access type, and (4) patient
      preference. Future studies evaluating the timing and type of vascular access with
      careful assessments of complications, functionality, cost benefit, and patients'
      preference will provide relevant information to individualize and optimize care
      to improve morbidity, mortality, and quality of life in the elderly patient.

PMID- 23173894
TI  - Age should be considered in the allocation of deceased donor kidneys.
AB  - Organ allocation is a specific example of the allocation of scarce resources in a
      pluralistic society. As such, it is subject to both governmental and public
      scrutiny. It must follow the requirements of the federal legislation and
      regulations regarding "equitable allocation of organs." An ideal allocation
      system should balance the ethical concepts of equity, or fairness, and utility,
      or usefulness. The current kidney allocation system has been in place, with some
      modifications over time, since the mid-1980s. It suffers from the changing
      demographics in ESRD, notably the aging of these groups, and in the growing
      length of the kidney waiting list. The current algorithm is thus imbalanced and
      requires reexamination. In particular, the system fails to match kidneys with
      long-projected function to recipients with long-projected lifespans, and vice
      versa. To improve the utility of kidney transplantation and lengthen the useful
      lifespan of these organs, a system that better matches kidneys and recipients is
      necessary, and this will require the use of recipient age in those calculations.
      The ethical questions and justification of such a system are presented.

PMID- 23173897
TI  - Evidence that an evolutionary transition from dehiscent to indehiscent fruits in
      Lepidium (Brassicaceae) was caused by a change in the control of valve margin
      identity genes.
AB  - In the Brassicaceae, indehiscent fruits evolved from dehiscent fruits several
      times independently. Here we use closely related wild species of the genus
      Lepidium as a model system to analyse the underlying developmental genetic
      mechanisms in a candidate gene approach. ALCATRAZ (ALC), INDEHISCENT (IND),
      SHATTERPROOF1 (SHP1) and SHATTERPROOF2 (SHP2) are known fruit developmental genes
      of Arabidopsis thaliana that are expressed in the fruit valve margin governing
      dehiscence zone formation. Comparative expression analysis by quantitative RT
      PCR, Northern blot and in situ hybridization show that their orthologues from
      Lepidium campestre (dehiscent fruits) are similarly expressed at valve margins.
      In sharp contrast, expression of the respective orthologues is abolished in the
      corresponding tissue of indehiscent Lepidium appelianum fruits, indicating that
      changes in the genetic pathway identified in A. thaliana caused the transition
      from dehiscent to indehiscent fruits in the investigated species. As parallel
      mutations in different genes are quite unlikely, we conclude that the changes in
      gene expression patterns are probably caused by changes in upstream regulators of
      ALC, IND and SHP1/2, possible candidates from A. thaliana being FRUITFULL (FUL),
      REPLUMLESS (RPL) and APETALA2 (AP2). However, neither expression analyses nor
      functional tests in transgenic plants provided any evidence that the FUL or RPL
      orthologues of Lepidium were involved in evolution of fruit indehiscence in
      Lepidium. In contrast, stronger expression of AP2 in indehiscent compared to
      dehiscent fruits identifies AP2 as a candidate gene that deserves further
      investigation.

PMID- 23173898
TI  - Novel OTOA mutations cause autosomal recessive non-syndromic hearing impairment
      in Pakistani families.

PMID- 23173899
TI  - Clinical comparison of the Welch Allyn SureSightTM handheld autorefractor vs.
      streak retinoscopy in dogs.
AB  - OBJECTIVE: To compare the Welch Allyn SureSightTM wavefront autorefractor with
      retinoscopy in normal dogs. ANIMALS STUDIED: Fifty privately owned dogs (100
      eyes) of 20 breeds, free of ocular disease. Mean +/- SD age: 5.7 +/- 3.25 years
      (range: 6 months-13 years). PROCEDURES: The refractive error was determined in
      each eye by two experienced retinoscopists using streak retinoscopy as well as by
      an autorefractor operated by two different examiners. Measurements were performed
      before and approximately 30-45 min after cycloplegia was induced by
      cyclopentolate 0.5% and tropicamide 0.5% ophthalmic solutions. RESULTS: Mean +/-
      SD noncyclopleged retinoscopy net sphere was -0.55 +/- 1.14 (range: -3.75 to 3.5)
      diopters (D). Mean cyclopleged retinoscopy net sphere was -0.52 +/- 1.18 (range: 
      4.25 to 2) D. Mean +/- SD noncyclopleged autorefractor spherical equivalent (SE)
      was -0.42 +/- 1.13 D (range: -3.36 to 2.73) D. Mean cyclopleged autorefractor SE
      was 0.10 +/- 1.47 (range: -5.62 to 3.19) D. Noncyclopleged autorefraction results
      were not significantly different from streak retinoscopy (whether noncyclopleged
      or cyclopleged, P = 0.80 and P = 0.26, respectively). Cyclopleged autorefraction
      results were significantly different from noncyclopleged or cyclopleged streak
      retinoscopy (P < 0.0001 in both states). There was no significant difference
      between noncyclopleged and cyclopleged streak retinoscopy (P = 0.97).
      CONCLUSIONS: Noncyclopleged autorefraction shows good agreement with streak
      retinoscopy in dogs and may be a useful clinical technique. Cycloplegia does not
      significantly affect streak retinoscopy results in dogs.

PMID- 23173900
TI  - Reaction wood - a key cause of variation in cell wall recalcitrance in willow.
AB  - BACKGROUND: The recalcitrance of lignocellulosic cell wall biomass to
      deconstruction varies greatly in angiosperms, yet the source of this variation
      remains unclear. Here, in eight genotypes of short rotation coppice willow (Salix
      sp.) variability of the reaction wood (RW) response and the impact of this
      variation on cell wall recalcitrance to enzymatic saccharification was
      considered. RESULTS: A pot trial was designed to test if the 'RW response' varies
      between willow genotypes and contributes to the differences observed in cell wall
      recalcitrance to enzymatic saccharification in field-grown trees. Biomass
      composition was measured via wet chemistry and used with glucose release yields
      from enzymatic saccharification to determine cell wall recalcitrance. The levels
      of glucose release found for pot-grown control trees showed no significant
      correlation with glucose release from mature field-grown trees. However, when a
      RW phenotype was induced in pot-grown trees, glucose release was strongly
      correlated with that for mature field-grown trees. Field studies revealed a 5
      fold increase in glucose release from a genotype grown at a site exposed to high
      wind speeds (a potentially high RW inducing environment) when compared with the
      same genotype grown at a more sheltered site. CONCLUSIONS: Our findings provide
      evidence for a new concept concerning variation in the recalcitrance to enzymatic
      hydrolysis of the stem biomass of different, field-grown willow genotypes (and
      potentially other angiosperms). Specifically, that genotypic differences in the
      ability to produce a response to RW inducing conditions (a 'RW response')
      indicate that this RW response is a primary determinant of the variation observed
      in cell wall glucan accessibility. The identification of the importance of this
      RW response trait in willows, is likely to be valuable in selective breeding
      strategies in willow (and other angiosperm) biofuel crops and, with further work
      to dissect the nature of RW variation, could provide novel targets for genetic
      modification for improved biofuel feedstocks.

PMID- 23173901
TI  - Development and experimental test of support vector machines virtual screening
      method for searching Src inhibitors from large compound libraries.
AB  - BACKGROUND: Src plays various roles in tumour progression, invasion, metastasis,
      angiogenesis and survival. It is one of the multiple targets of multi-target
      kinase inhibitors in clinical uses and trials for the treatment of leukemia and
      other cancers. These successes and appearances of drug resistance in some
      patients have raised significant interest and efforts in discovering new Src
      inhibitors. Various in-silico methods have been used in some of these efforts. It
      is desirable to explore additional in-silico methods, particularly those capable
      of searching large compound libraries at high yields and reduced false-hit rates.
      RESULTS: We evaluated support vector machines (SVM) as virtual screening tools
      for searching Src inhibitors from large compound libraries. SVM trained and
      tested by 1,703 inhibitors and 63,318 putative non-inhibitors correctly
      identified 93.53%~ 95.01% inhibitors and 99.81%~ 99.90% non-inhibitors in 5-fold
      cross validation studies. SVM trained by 1,703 inhibitors reported before 2011
      and 63,318 putative non-inhibitors correctly identified 70.45% of the 44
      inhibitors reported since 2011, and predicted as inhibitors 44,843 (0.33%) of
      13.56M PubChem, 1,496 (0.89%) of 168 K MDDR, and 719 (7.73%) of 9,305 MDDR
      compounds similar to the known inhibitors. CONCLUSIONS: SVM showed comparable
      yield and reduced false hit rates in searching large compound libraries compared
      to the similarity-based and other machine-learning VS methods developed from the
      same set of training compounds and molecular descriptors. We tested three virtual
      hits of the same novel scaffold from in-house chemical libraries not reported as
      Src inhibitor, one of which showed moderate activity. SVM may be potentially
      explored for searching Src inhibitors from large compound libraries at low false
      hit rates.

PMID- 23173903
TI  - Methods: implementation of in vitro and ex vivo phagocytosis and respiratory
      burst function assessments in safety testing.
AB  - Functional innate immune assessments, including phagocytosis and respiratory
      burst, are at the forefront of immunotoxicology evaluation in pre-clinical animal
      species. Although in the clinic and in academic science, phagocytosis, and
      respiratory burst assessments have been reported for over two decades, the
      implementation of phagocytosis and respiratory burst analyses in toxicology
      safety programs is just recently gaining publicity. Discussed herein are general
      methods, both microtiter plate-based and flow cytometric-based, for assessing
      phagocytosis and respiratory burst in pre-clinical species including mouse, rat,
      dog, and monkey. This methods-centric discussion includes a review of
      technologies and descriptions of method applications, with examples of results
      from analyses testing reported inhibitors (rottlerin, wortmannin, and SB203580)
      of phagocytosis and respiratory burst. Justification of implementation, strategic
      experimental design planning, and feasibility aspects of evaluating test article
      effects on phagocytosis and respiratory burst function are described within the
      context of a case study. The case study involves investigation of the effects of
      a small molecule p38 kinase inhibitor, BMS-582949, on phagocytosis and
      respiratory burst functions in rat and monkey neutrophils and monocytes in vitro,
      as well as ex vivo in these innate immune cells from monkeys administered BMS
      582949 during a 1-week repeat dose investigative study. The results of the in
      vitro and ex vivo assessments demonstrated that BMS-582949 inhibited phagocytosis
      and respiratory burst. These findings correlated with incidences of opportunistic
      infections observed in rat and monkey toxicity studies.

PMID- 23173902
TI  - Is the Scale for Measuring Motivational Interviewing Skills a valid and reliable
      instrument for measuring the primary care professionals motivational skills?:
      EVEM study protocol.
AB  - BACKGROUND: Lifestyle is one of the main determinants of people's health. It is
      essential to find the most effective prevention strategies to be used to
      encourage behavioral changes in their patients. Many theories are available that
      explain change or adherence to specific health behaviors in subjects. In this
      sense the named Motivational Interviewing has increasingly gained relevance. Few
      well-validated instruments are available for measuring doctors' communication
      skills, and more specifically the Motivational Interviewing. METHODS/DESIGN: The
      hypothesis of this study is that the Scale for Measuring Motivational
      Interviewing Skills (EVEM questionnaire) is a valid and reliable instrument for
      measuring the primary care professionals skills to get behavior change in
      patients. To test the hypothesis we have designed a prospective, observational,
      multi-center study to validate a measuring instrument. - SCOPE: Thirty-two
      primary care centers in Spain. -Sampling and Size: a) face and consensual
      validity: A group composed of 15 experts in Motivational Interviewing. b)
      Assessment of the psychometric properties of the scale; 50 physician- patient
      encounters will be videoed; a total of 162 interviews will be conducted with six
      standardized patients, and another 200 interviews will be conducted with 50 real
      patients (n=362). Four physicians will be specially trained to assess 30
      interviews randomly selected to test the scale reproducibility. -Measurements for
      to test the hypothesis: a) Face validity: development of a draft questionnaire
      based on a theoretical model, by using Delphi-type methodology with experts. b)
      Scale psychometric properties: intraobservers will evaluate video recorded
      interviews: content-scalability validity (Exploratory Factor Analysis), internal
      consistency (Cronbach alpha), intra-/inter-observer reliability (Kappa index,
      intraclass correlation coefficient, Bland & Altman methodology),
      generalizability, construct validity and sensitivity to change (Pearson product
      moment correlation coefficient). DISCUSSION: The verification of the hypothesis
      that EVEM is a valid and reliable tool for assessing motivational interviewing
      would be a major breakthrough in the current theoretical and practical knowledge,
      as it could be used to assess if the providers put into practice a patient
      centered communication style and can be used both for training or researching
      purposes. TRIALS REGISTRATION Dislip-EM study: NCT01282190 (ClinicalTrials.gov).

PMID- 23173904
TI  - Predictors of long-term smoking cessation: results from the global adult tobacco
      survey in Poland (2009-2010).
AB  - BACKGROUND: Expanding the information on determinants of smoking cessation is
      crucial for developing and implementing more effective tobacco control measures
      at the national as well as European levels. Data on smoking cessation and its
      social correlates among adults from middle-income countries of Central and
      Eastern Europe are still poorly reported in the literature. The aim of the study
      was to analyze the association of socio-demographic indicators with long term
      tobacco smoking cessation (quit smoking for at least one year prior to interview)
      among adults. Moreover, we evaluated motives for giving up smoking from former
      smokers. METHODS: Data on former as well as current smokers' socio-demographic
      and smoking-related characteristics were derived from the Global Adult Tobacco
      Survey (GATS). GATS is a cross-sectional, nationally representative household
      survey implemented in Poland between 2009 and 2010. GATS collected data on a
      representative sample of 7,840 individuals including 1,206 individuals who met
      the criteria of long-term smoking cessation and 2,233 current smokers. Smoking
      cessation rate was calculated as the number of former smokers divided by the
      number of ever smokers. Logistic regression analyses were used to obtain odds
      ratios (ORs) and 95% confidence interval (CI) of the broad number of variables on
      successful cessation of smoking. RESULTS: Among females the quit rate was 30.4%
      compared to 37.9% in males (p < 0.01). Former smokers declared concerns about the
      health hazard of smoking (60.8%) and the high price of cigarettes (11.6%) as
      primary reasons for smoking cessation. Older age, high education attainment,
      awareness of smoking health consequences was associated with long-term quitting
      among both genders. Also employed males had over twice the probability of giving
      up smoking compared with unemployed, and being religious did not contribute to
      successful smoking cessation. CONCLUSION: Results indicated that smoking
      cessation policies focused on younger age groups are vital for curbing tobacco
      epidemic in Poland and should become a public health main concern. There is also
      the need for interventions to raise awareness on smoking health risks and
      quitting benefits are crucial to increase cessation potential among adult
      smokers. Nevertheless further effort needs to be done to prevent smoking uptake.

PMID- 23173905
TI  - The retention of health human resources in primary healthcare centers in Lebanon:
      a national survey.
AB  - BACKGROUND: Critical shortages of health human resources (HHR), associated with
      high turnover rates, have been a concern in many countries around the globe. Of
      particular interest is the effect of such a trend on the primary healthcare (PHC)
      sector; considered a cornerstone in any effective healthcare system. This study
      is a rare attempt to investigate PHC HHR work characteristics, level of burnout
      and likelihood to quit as well as the factors significantly associated with staff
      retention at PHC centers in Lebanon. METHODS: A cross-sectional design was
      utilized to survey all health providers at 81 PHC centers dispersed in all
      districts of Lebanon. The questionnaire consisted of four sections: socio
      demographic/ professional background, organizational/institutional
      characteristics, likelihood to quit and level of professional burnout (using the
      Maslach-Burnout Inventory). A total of 755 providers completed the questionnaire
      (60.5% response rate). Bivariate analyses and multinomial logistic regression
      were used to determine factors associated with likelihood to quit. RESULTS: Two
      out of five respondents indicated likelihood to quit their jobs within the next 1
      3 years and an additional 13.4% were not sure about quitting. The top three
      reasons behind likelihood to quit were poor salary (54.4%), better job
      opportunities outside the country (35.1%) and lack of professional development
      (33.7%). A U-shaped relationship was observed between age and likelihood to quit.
      Regression analysis revealed that high levels of burnout, lower level of
      education and low tenure were all associated with increased likelihood to quit.
      CONCLUSIONS: The study findings reflect an unstable workforce and are not
      conducive to supporting an expanded role for PHC in the Lebanese healthcare
      system. While strategies aiming at improving staff retention would be important
      to develop and implement for all PHC HHR; targeted retention initiatives should
      focus on the young-new recruits and allied health professionals. Particular
      attention should be dedicated to enhancing providers' role satisfaction and sense
      of job security. Such initiatives are of pivotal importance to stabilize the
      workforce and ensure its longevity.

PMID- 23173906
TI  - Malaysian government dentists' experience, willingness and barriers in providing
      domiciliary care for elderly people.
AB  - OBJECTIVE: To assess Malaysian government dentists' experience, willingness and
      barriers in providing domiciliary care for elderly people. MATERIAL AND METHODS:
      A descriptive cross-sectional study was conducted using a self-administered
      postal questionnaire targeting government dentists working in the Ministry of
      Health in Peninsular Malaysia. RESULTS: Seven hundred and eleven out of 962
      dentists responded with a response rate of 74.0%. Only 36.1% of the dentists had
      experience in providing domiciliary care for elderly people in the past 2 years
      with mean number of visit per year of 1. Younger dentists below the age of 30 and
      those with confidence in providing the service were the most willing to undertake
      domiciliary care for elderly patients (OR=13.5, p<0.05). The 3 most reported
      barriers were patient's complex medical history (74.1%), patient's poor attitude
      towards oral health service (67.5%), and dentist's unfavourable working condition
      (64.4%). CONCLUSION: The majority of Malaysian government dentists had not been
      involved in providing domiciliary care for elderly patients. Apart from
      overcoming the barriers, other recommendations include improving undergraduate
      dental education, education for elderly people and carers, improving dentist's
      working condition, and introducing domiciliary financial incentive for dentist.

PMID- 23173907
TI  - Pathology, a path well worn.

PMID- 23173908
TI  - Biological effects of short-term salmon oil administration, using distinct salmon
      oil sources in healthy dogs.
AB  - OBJECTIVES: To assess the short-term effects of feeding distinct salmon oil
      sources in healthy dogs. METHODS: A diet containing chicken fat as major fat
      source was fed to 17 dogs for 14 days. For the next 14 days, dogs received one of
      two diets, both with 1% of chicken fat exchanged for 1% salmon oil; Norwegian or
      Scottish salmon oil, harvested using a distinct procedure. Finally, all dogs were
      fed chicken fat again for 14 days. RESULTS: Salmon oil increased serum
      phospholipid total n-3 polyunsaturated fatty acids, eicosapentaenoic and
      docosahexaenoic acid and decreased total n-6 polyunsaturated fatty acids and n
      6:n-3. The phospholipid fatty acid profile returned to initial values within 2
      weeks of discontinuing salmon oil administration. Blood coagulation, acute phase
      response and plasma immunoglobulin concentrations were not affected by salmon oil
      and no differences were detected for the measured indices between the two salmon
      oils. CLINICAL SIGNIFICANCE: Low-dose salmon oil administration alters serum
      phospholipid fatty acid profile within 2 weeks, but without affecting selected
      immunologic and coagulation indices. Salmon oil sources from different sources
      and harvested using a distinct procedure did not induce different effects, most
      probably because of their similar fatty acid profiles.

PMID- 23173909
TI  - Drug reaction with eosinophilia and systemic symptoms syndrome associated
      myocarditis: a survival experience after extracorporeal membrane oxygenation
      support.
AB  - WHAT IS KNOWN AND OBJECTIVE: Myocarditis that develops because of the drug
      reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a life
      threatening disease. We report a case of DRESS-associated myocarditis with
      cardiac failure that required extracorporeal membrane oxygenation (ECMO) for
      cardiovascular support. CASE SUMMARY: A 14-year-old boy experienced DRESS
      associated myocarditis after anticonvulsive therapy with carbamazepine,
      clonazepam and phenytoin. The clinical signs included hypotension, cardiac
      arrhythmia and poor left ventricular (LV) performance. Laboratory investigations
      showed elevated levels of cardiac enzymes. Systemic corticosteroid pulse therapy
      for 3 days was administered for treating the DRESS syndrome. The patient required
      inotropic drugs including dopamine, dobutamine and milrinone because of
      refractory hypotension and poor LV function. He was placed on ECMO support, and
      intra-aortic balloon pumping was initiated because of poor response to inotropic
      drugs and stasis of blood flow in the ventricle on hospital day 17. Plasma
      exchanges for four separate times over 8 days were also performed during ECMO
      support on day 22. His condition stabilized 13 days after ECMO support was
      initiated. The patient was discharged on hospital day 50, and the seizure was
      controlled by the oral form clonazepam, phenobarbital, topiramate and
      levetiracetam. Three months later, an echocardiogram showed mild dilated
      cardiomyopathy. WHAT IS NEW AND CONCLUSION: Drug reaction with eosinophilia and
      systemic symptoms-associated fulminant myocarditis is a life-threatening disease.
      Traditionally, systemic corticosteroid administration, plasmapheresis,
      intravenous immunoglobulin infusion and ventricular assist device implantation
      have been used for the treatment of this disease. To our knowledge, this is the
      first case of DRESS-associated fulminant myocarditis treated successfully with
      ECMO support. However, echocardiogram should be followed regularly because
      dilated cardiomyopathy may be the late sequela.

PMID- 23173910
TI  - Early biocompatibility of poly (ethylene glycol) hydrogel barrier materials for
      guided bone regeneration. An in vitro study using human gingival fibroblasts (HGF
      1).
AB  - OBJECTIVES: To evaluate the early cellular attachment and viability to modified
      polyethylene glycol (PEG) hydrogels with the influence of arginine-glycine
      aspartic acid (RGD) in an in vitro model system. MATERIAL AND METHODS: Human
      gingival fibroblasts (HGF-1) were cultured on 6 different modalities of PEG
      hydrogel in hydrophobic polystyrene wells. A total of 7500 cells/well (10,000
      cells/cm(2)) were dispersed over the PEG filled wells and incubated in
      triplicates for 24 h, 7 and 13 days. Cell numbers were calculated by means of a
      NucleoCounter. Cell viability was determined by measuring lactate dehydrogenase
      (LDH). For statistical analysis, nonparametric Kruska-Wallis test followed by
      Dunetts T3 test were used. RESULTS: All PEG modifications showed good
      biocompatibility, as demonstrated by low LDH values per cell at the earlier two
      time points. After 13 days, all PEG modifications showed significantly lower
      number of cells compared with the controls, and the MX60 configurations
      demonstrated significantly higher LDH/cell values compared with the other
      hydrogels. CONCLUSIONS: Modifications of the physio-chemical properties of PEG
      hydrogels and the addition of RGD and spacers influenced the initial cellular
      response of cultured HGF-1 cells. With the exception of MX60 after 13 days, all
      PEG formulations performed similarly well. Early cellular response should be
      considered when developing PEG-based material for clinical purposes.

PMID- 23173911
TI  - Comment and reply on: Vasohibin-1 and its emerging role in the evolution and
      progression of systemic tumors besides renal cell carcinomas.

PMID- 23173912
TI  - A hierarchical coherent-gene-group model for brain development.
AB  - We have described a strategy to analyze the data available on brain genes
      expression, using the concept of coherent-gene groups controlled by transcription
      factors (TFs). A hierarchical model of gene-expression patterns during brain
      development was established that identified the genes assumed to behave as
      functionally coding. Analysis of the concerned signaling pathways and processes
      showed distinct temporal gene-expression patterns in relation with
      neurogenesis/synaptogenesis. We identified the hierarchical tree of TF networks
      that determined the patterns of genes expressed during brain development. Some
      'master TFs' at the top level of the hierarchy regulated the expression of gene
      groups. Enhanced/decreased activity of a few master TFs may explain paradoxes
      raised by the genetic determination of autism-spectrum disorders and
      schizophrenia. Our analysis showed gene-TF networks, common or related, to these
      disorders that exhibited two maxima of expression, one in the prenatal and the
      other at early postnatal period of development, consistent with the view that
      these disorders originate in the prenatal period, develop in the postnatal
      period, and reach the ultimate neural and behavioral phenotype with different
      sets of genes regulating each of these periods. We proposed a strategy for drug
      design based upon the temporal patterns of expression of the concerned TFs.
      Ligands targeting specific TFs can be designed to specifically affect the
      pathological evolution of the mutated gene(s) in genetically predisposed patients
      when administered at relevant stages of brain development.

PMID- 23173913
TI  - TIMELESS is overexpressed in lung cancer and its expression correlates with poor
      patient survival.
AB  - TIMELESS (TIM) is a mammalian homolog of a Drosophila circadian rhythm gene, but
      its circadian properties in mammals have yet to be determined. TIM appears to be
      essential for replication protection and genomic stability. Recently, the
      involvement of TIM in human malignancies has been reported; therefore, we
      investigated the role of TIM in lung cancer. Microarray expression analysis of
      lung cancer cell lines showed that TIM expression was elevated 3.7-fold (P <
      0.001) in non-small cell lung cancer cell lines (n = 116) compared to normal lung
      controls (n = 59). In addition, small cell lung cancer cell lines (n = 29)
      expressed TIM at levels 2.2-fold (P < 0.001) higher than non-small cell lung
      cancer. Western blot analysis of 22 lung cancer cell lines revealed that all of
      them expressed TIM protein and that 20 cell lines (91%) expressed TIM protein at
      higher levels than a normal control line. Remarkably, immunohistochemistry of 30
      surgically resected lung cancer specimens showed that all lung cancer specimens
      but no matched normal lung tissues were positive for TIM expression. Moreover,
      immunohistochemistry of surgically resected specimens from 88 consecutive
      patients showed that high TIM protein levels correlated with poor overall
      survival (P = 0.013). Mutation analysis for TIM in 23 lung cancer cell lines
      revealed no mutation. TIM knockdown suppressed proliferation and clonogenic
      growth, and induced apoptosis in H157 and H460 cells. Taken together, our
      findings suggest that TIM could be useful as a diagnostic and prognostic marker
      for lung cancer and targeting it would be of high therapeutic value for this
      disease.

PMID- 23173914
TI  - Assessments used to diagnose developmental coordination disorder: do their
      underlying constructs match the diagnostic criteria?
AB  - This study examined the constructs underlying the Movement Assessment Battery for
      Children-2 (M-ABC-2), Bruninks-Oseretsky Test of Motor Proficiency (BOTMP) and
      Vineland Adaptive Behavior Scale-2 (VABS-2) using the framework of the
      International Classification of Functioning Disability and Health-Child Youth
      version (ICF-CY) and the diagnostic criteria of developmental coordination
      disorder (DCD). Two independent raters coded and matched items to ICF-CY codes as
      per the eight ICF linking rules developed by Cierza and colleagues. Content
      density and inter-rater reliability were also calculated. The majority of codes
      assigned to the M-ABC-2 and BOTMP related to body functions (54% and 64%
      respectively). For the VABS-2, 91% of codes pertained to activities and
      participation. The M-ABC-2, BOTMP, and the VABS-2 emphasize the ICF-CY constructs
      differently. The VABS-2 may be useful in the evaluation of performance of daily
      life activities and participation in children with DCD.

PMID- 23173915
TI  - Plant lighting system with five wavelength-band light-emitting diodes providing
      photon flux density and mixing ratio control.
AB  - BACKGROUND: Plant growth and development depend on the availability of light.
      Lighting systems therefore play crucial roles in plant studies. Recent
      advancements of light-emitting diode (LED) technologies provide abundant
      opportunities to study various plant light responses. The LED merits include
      solidity, longevity, small element volume, radiant flux controllability, and
      monochromaticity. To apply these merits in plant light response studies, a
      lighting system must provide precisely controlled light spectra that are useful
      for inducing various plant responses. RESULTS: We have developed a plant lighting
      system that irradiated a 0.18 m2 area with a highly uniform distribution of
      photon flux density (PFD). The average photosynthetic PFD (PPFD) in the
      irradiated area was 438 micro-mol m-2 s-1 (coefficient of variation 9.6%), which
      is appropriate for growing leafy vegetables. The irradiated light includes
      violet, blue, orange-red, red, and far-red wavelength bands created by LEDs of
      five types. The PFD and mixing ratio of the five wavelength-band lights are
      controllable using a computer and drive circuits. The phototropic response of oat
      coleoptiles was investigated to evaluate plant sensitivity to the light control
      quality of the lighting system. Oat coleoptiles irradiated for 23 h with a
      uniformly distributed spectral PFD (SPFD) of 1 micro-mol m-2 s-1 nm-1 at every
      peak wavelength (405, 460, 630, 660, and 735 nm) grew almost straight upwards.
      When they were irradiated with an SPFD gradient of blue light (460 nm peak
      wavelength), the coleoptiles showed a phototropic curvature in the direction of
      the greater SPFD of blue light. The greater SPFD gradient induced the greater
      curvature of coleoptiles. The relation between the phototropic curvature (deg)
      and the blue-light SPFD gradient (micro-mol m-2 s-1 nm-1 m-1) was 2 deg per 1
      micro-mol m-2 s-1 nm-1 m-1. CONCLUSIONS: The plant lighting system, with a
      computer with a graphical user interface program, can control the PFD and mixing
      ratios of five wavelength-band lights. A highly uniform PFD distribution was
      achieved, although an intentionally distorted PFD gradient was also created.
      Phototropic responses of oat coleoptiles to the blue light gradient demonstrated
      the merit of fine controllability of this plant lighting system.

PMID- 23173917
TI  - Morphological markers for the detection of introgression from cultivated into
      wild carrot (Daucus carota L.) reveal dominant domestication traits.
AB  - Hybridisation and subsequent introgression have recently received much attention
      in the context of genetically modified crops. But crop-wild hybrid detection in
      the field can be difficult, as most domestication traits seem to be recessive,
      and the hybrid phenotype may also depend on the direction of the cross or
      environmental factors. Our aim was to develop a reliable set of morphological
      markers that differ between two wild and 13 cultivated carrots (Daucus carota L.)
      and to evaluate their inheritance in hybrid lines. We then examined these
      morphological markers in four F1 hybrids obtained by fertilising plants from the
      two wild accessions with pollen from two common carrot cultivars. Of the 16
      traits that differed between the two carrot subspecies, three took intermediate
      values in the hybrids, eight resembled the cultivar parent (dominant
      domestication traits), two resembled the wild parent (domestication traits
      recessive), and three were not significant or growth condition-dependent.
      Root:shoot ratio was seven times higher for cultivars than for wild plants, while
      still attaining equivalent total dry weight, which shows that dry matter
      production by the shoot is much higher in cultivars than in wild plants. High
      root:shoot ratios were also present in the hybrids. While we found no maternal
      effects, the type of cultivar used for pollination had an impact on hybrid
      characteristics. The morphological markers developed here provide insights into
      the mode of inheritance of ecologically relevant traits and can be useful for pre
      screening wild populations for hybrid detection prior to genetic analysis.

PMID- 23173919
TI  - Thyroid surgery in geriatric patients: a literature review.
AB  - BACKGROUND: Thyroid disease is common in the elderly population. The incidence of
      hypothyroidism and multinodular goitre gradually increases with age. In view of a
      growth of aging population, we performed a literature review about the
      feasibility of thyroid surgery in the elderly. METHODS: We conducted a literature
      search in the PubMed database in September 2012 and all English-language
      publications on thyroidectomy in geriatric patients since 2002 were retrieved.
      The potential original articles mainly focusing on thyroidectomy in elderly
      patients were all identified and full texts were obtained and reviewed for
      further hand data retrieving. RESULTS: We retrieved five papers based on
      different primary end-point. Four were retrospective non randomized studies and
      one was prospective non randomized study. At last 65, 70, 75 and 80 years were
      used as an age cut-off. All studies evaluate the indications of thyroidectomy in
      geriatric patients, postoperative morbility and mortality. Only one study
      specifically assesses the rate of the rehospitalization after thyroidectomy among
      the elderly. CONCLUSIONS: Thyroid nodules are particularly important in elderly
      patients, as the incidence of malignancy increases and they are usually more
      aggressive tumors. An age of at least 70 years is an independent risk factor for
      complications after general surgery procedures. Thyroid surgery in patients aged
      70 years or older is safe and the relatively high rate of thyroid carcinoma and
      toxic goiter may justify an aggressive approach. A programmed operation with a
      careful pre-operative evaluation and a risk stratification should make the
      surgical procedures less hazardous, specially in 80 years old patients with an
      high ASA score.

PMID- 23173918
TI  - Difficult colonoscopies in the propofol era.
AB  - BACKGROUND: To study the relationship between endoscopic practice and adverse
      events during colonoscopy under standard deep sedation induced and monitored by
      an anesthetist. METHODS: We investigated the routine activity of an endoscopy
      center at the Padova University teaching hospital. We considered not only
      endoscopic and cardiorespiratory complications, but also the need to use high
      dose propofol to complete the procedure, and the inability to complete the
      procedure. Variables relating to the patient's clinical conditions, bowel
      preparation, the endoscopist's and the anesthetist's experience, and the duration
      of the procedure were input in the model. RESULTS: 617 procedures under deep
      sedation were performed with a 5% rate of adverse events. The average dose of
      propofol used was 2.6 +/- 1.2 mg/kg. In all, 14 endoscopists and 42 anesthetists
      were involved in the procedures. The logistic regression analysis identified
      female gender (OR=2.3), having the colonoscopy performed by a less experienced
      endoscopist (OR=1.9), inadequate bowel preparation (OR=3.2) and a procedure
      lasting longer than 17.5 minutes (OR=1.6) as the main risk factors for
      complications. An ASA score of 2 carried a 50% risk reduction (OR=0.5).
      DISCUSSION AND CONCLUSIONS: Our model showed that none of the variables relating
      to anesthesiological issues influenced which procedures would prove difficult.

PMID- 23173916
TI  - Striatocortical pathway dysfunction in addiction and obesity: differences and
      similarities.
AB  - Neuroimaging techniques are starting to reveal significant overlap in the brain
      circuitry underlying addiction and disorders of dyscontrol over rewarding
      behaviors (such as binge eating disorder and obesity). Positron emission
      tomography (PET) has demonstrated impaired striatal dopamine (DA) signaling
      (decreased D2 receptors) in drug addiction and obesity that is associated with
      reduced baseline glucose metabolism in medial and ventral prefrontal brain
      regions. Functional magnetic resonance imaging (fMRI) has documented brain
      activation abnormalities that also implicate DA-modulated striato-cortical
      pathways. In this review we map findings from recent neuroimaging studies that
      differentiate brain activation in drug/food addiction from those in controls
      within brain networks functionally connected with ventral and dorsal striatum. We
      show that regions found to be abnormal in addiction and obesity frequently emerge
      at the overlap of the dorsal and the ventral striatal networks. Medial temporal
      and superior frontal regions functionally connected with dorsal striatum display
      greater vulnerability in obesity and eating disorders than in drug addictions,
      indicating more widespread abnormalities for obesity and eating disorders than
      for addictions. This corroborates involvement of both ventral striatal
      (predominantly associated with reward and motivation) and dorsal striatal
      networks (associated with habits or stimulus response learning) in addiction and
      obesity but also identify distinct patterns between these two disorders.

PMID- 23173920
TI  - Probing the contacts of a low-affinity substrate with a membrane-embedded
      transport protein using 1H-13C cross-polarisation magic-angle spinning solid
      state NMR.
AB  - Solid-state NMR combined with sample deuteration was used to probe the proximity
      of the low-affinity substrate D-glucose to its binding site within the
      Escherichia coli sugar transport protein GalP. Samples of E. coli inner membranes
      with amplified expression of GalP were incubated in D(2)O with D
      [(13)C(6)]glucose and (13)C NMR signals from the substrate were assigned in two
      dimensional dipolar-assisted rotational resonance (DARR) spectra. The signals
      were confirmed as representing D-glucose bound to GalP as the peaks were
      abolished after the substrate was displaced from the specific site with the
      inhibitor forskolin. The (13)C chemical shift values for D-[(13)C(6)]glucose in
      solution revealed some differences compared to those for ligand bound to GalP,
      the differences being most pronounced for positions C1 and C2, and especially for
      C1 in the alpha-anomer. (13)C cross-polarization build-up was measured for C1 and
      C2 of D-[(13)C(6)]glucose and D-[(2)H(7), (13)C(6)]glucose in GalP membranes
      suspended in D(2)O. The build-up curves for the deuterated substrate reflect
      intermolecular (1)H-(13)C interactions between the protein and the fully
      deuterated substrate; the signal build-up suggests that the alpha-anomer is
      situated closer to the protein binding site than is the beta-anomer, consistent
      with its relatively high signal intensities and more pronounced chemical shift
      changes in the 2D-correlation spectra. These results demonstrate the utility of
      solid-state NMR combined with sample deuteration for mapping the binding
      interface of low affinity ligands with membrane proteins.

PMID- 23173921
TI  - Hofmeister phenomena in nonaqueous media: the solubility of electrolytes in
      ethylene carbonate.
AB  - The solubility of some potassium salts (KF, KCl, KBr, KI, KNO(3), KClO(4), KSCN,
      and KSeCN) in ethylene carbonate (EC) was determined at different temperatures
      with an inductively coupled plasma atomic emission spectrometer. From the
      solubility measurements, the thermodynamic parameters DeltaG, DeltaH, and DeltaS,
      of solution and of solvation, were calculated. Measurements were carried out via
      XRD, ATR, and FTIR to determine the effect of each salt on the properties of the
      solvent. The open question of whether specific ion (Hofmeister) effects are
      restricted to hydration peculiar to water is resolved. As for water, the effects
      are due to solute (ion, dipolar) induced solvent structure not accounted for by
      electrostatic forces. Cooperative quantum mechanical forces are necessary to
      understand the phenomena.

PMID- 23173922
TI  - Diverticular disease hospital cost impact analysis: evaluation of testings and
      surgical procedures in inpatient and outpatient admissions.
AB  - BACKGROUND: Diverticular Disease (DD) is a common condition in Italy and in other
      western countries. There is not much data concerning DD's impact on budget and
      activity in hospitals. METHODS: The aim is to detect the clinical workload and
      the financial impact of diverticular disease in hospitals.Retrospective
      observational study of all patients treated for diverticular disease during the
      period of seven years in AOU Federico II. Analysis of inpatient and outpatient
      investigations, treatment, hospitalization and financial refunds. RESULTS: A
      total of 738 patients were treated and 840 hospital discharge records were
      registered. There were a total number of 4101 hospitalization days and 753
      outpatient accesses. The investigations generated were 416 endoscopies, 197
      abdominal CT scans, 177 abdominal ultrasound scans, 109 X-rays tests. A total of
      193 surgical operations were performed. The total cost of this activity was ?
      1.656.802 or 0.2% of the total budget of the hospital. ? 1.346.218, were
      attributable to the department of general surgery, 0.9% of the department's
      budget . CONCLUSIONS: The limited impact of diverticular disease on the budget
      and activity of AOU Federico II of Naples is mainly due to the absence of an
      emergency department.

PMID- 23173923
TI  - The effects of a selective inhibitor of c-Fos/activator protein-1 on endotoxin
      induced acute kidney injury in mice.
AB  - BACKGROUND: Sepsis has been identified as the most common cause of acute kidney
      injury (AKI) in intensive care units. Lipopolysaccharide (LPS) induces the
      production of several proinflammatory cytokines including tumor necrosis factor
      (TNF)-alpha, a major pathogenetic factor in septic AKI. c-Fos/activator protein
      (AP)-1 controls the expression of these cytokines by binding directly to AP-1
      motifs in the cytokine promoter regions. T-5224 is a new drug developed by
      computer-aided drug design that selectively inhibits c-Fos/AP-1 binding to DNA.
      In this study, we tested whether T-5224 has a potential inhibitory effect against
      LPS-induced AKI, by suppressing the TNF-alpha inflammatory response and other
      downstream effectors. METHODS: To test this hypothesis, male C57BL/6 mice at 7
      weeks old were divided into three groups (control, LPS and T-5224 groups). Mice
      in the control group received saline intraperitoneally and polyvinylpyrrolidone
      solution orally. Mice in the LPS group were injected intraperitoneally with a 6
      mg/kg dose of LPS and were given polyvinylpyrrolidone solution immediately after
      LPS injection. In the T-5224 group, mice were administered T-5224 orally at a
      dose of 300 mg/kg immediately after LPS injection. Serum concentrations of TNF
      alpha, interleukin (IL)-1beta, IL-6 and IL-10 were measured by ELISA. Moreover,
      the expression of intercellular adhesion molecule (ICAM)-1 mRNA in kidney was
      examined by quantitative real-time RT-PCR. Finally, we evaluated renal
      histological changes. RESULTS: LPS injection induced high serum levels of TNF
      alpha, IL-1beta and IL-6. However, the administration of T-5224 inhibited the LPS
      induced increase in these cytokine levels. The serum levels of IL-10 in the LPS
      group and T-5224 group were markedly elevated compared with the control group. T
      5224 also inhibited LPS-induced ICAM-1 mRNA expression. Furthermore histological
      studies supported an anti-inflammatory role of T-5224. CONCLUSIONS: In endotoxin
      induced AKI, T-5224 inhibited the production of TNF-alpha and other downstream
      effectors. In contrast, T-5224 did not inhibit IL-10, an anti-inflammatory
      cytokine. These data support that the use of T-5224 is a promising new treatment
      for septic kidney injury.

PMID- 23173924
TI  - Flavonoids and linderone from Lindera oxyphylla and their bioactivities.
AB  - A new linderone A, namely 2-cinnamoyl-3-hydroxy-4, 5-dimethoxycyclopenta-2, 4
      dienone (5), together with three known flavonoids (1-3) and one linderone (4),
      were isolated from the bark of Lindera oxyphylla. Extensive spectroscopic
      analysis including 1D and 2D-NMR spectra determined their sturctures. In
      addition, the antioxidant activity of all the compounds has been determined using
      2, 2-diphenyl-1-picrylhydrazyl radical scavenging (DPPH), ferric reducing
      antioxidant power (FRAP) and ferrous ion chelating (FIC) methods. Compound 3
      showed excellent DPPH scavenging activity with IC50% value of 8.5 +/- 0.004%
      (MUg/mL) which is comparable with vitamin C. This compound, also showed an
      absorbance value of 1.00 +/- 0.06% through FRAP test when compared with Butyl
      Hydroxy Aniline (BHA). However, FIC showed low activity for all the isolated
      compounds (chelating activity less than 50%) in comparison with ethylene diamine
      tetra acetic acid (EDTA). Anticancer activity for all compounds has also been
      measured on A375 human melanoma, HT-29 colon adenocarcinoma, MCF-7 human breast
      adenocarcinoma cells, WRL-68 normal hepatic cells, A549 non-small cell lung
      cancer cells and PC-3 prostate adenocarcinoma cell line. Compound 1 showed
      A549=65.03%, PC-3=30.12%, MCF-7=47.67, compound 2 showed PC-3=90.13%, compound 3
      showed MCF-7=79.57 and for compound 5 MCF-7 is 96.33.

PMID- 23173925
TI  - Computational modelling of the volatile hydride fragmentation in a dielectric
      barrier discharge atomizer.
AB  - In this study, we present a model whereby a fragmentation of arsenic hydride in a
      rectangular dielectric barrier discharge (DBD) atomizer is investigated. The aim
      is to elucidate the distribution of the intermediates species and generated free
      analyte atoms along atomizer channel, which is required to decide the optimal
      position for spectrometric data acquisition. Simulation results indicate that
      formation of intermediate species and free arsenic atoms is initiated in the
      first section of atomization channel before reaching the section between the
      electrodes. Moreover, concentration of free arsenic atoms saturates to a maximum
      and does not vary thereafter along atomization channel. This result could be
      attributed to the presence of abundance of hydrogen radicals along atomization
      channel which limits recombination reactions and ultimately maintains free atom
      life, which is so useful for analytical purposes. This outcome suggests an
      approach for radial data acquisition from any position along DBD atomization
      channel with same sensitivity. Furthermore, this result indicates that DBD
      atomizer is appropriate for analytical purposes and competitive to other well
      known atomization tools such as a quartz cell atomizer. The model has been
      verified experimentally upon examining arsenic and mercury qualitatively from
      applying chemical vapour generation techniques. Approximately similar results
      obtained from three radial positions along the atomization channel, whereas a
      significant increase in signal intensity observed when applying axial viewing by
      22 and 40% for arsenic and mercury respectively. Furthermore, a quantitative
      determination for arsenic is also tried; however, the results were found not
      useful for model validation due to the hydrogen magnification effect on the
      recorded spectrum.

PMID- 23173926
TI  - Colostrum supplementation protects against exercise-induced oxidative stress in
      skeletal muscle in mice.
AB  - BACKGROUND: This study examined the effects of bovine colostrum on exercise 
      induced modulation of antioxidant parameters in skeletal muscle in mice. Adult
      male BALB/c mice were randomly divided into four groups (control, colostrum
      alone, exercise and exercise with colostrum) and each group had three subgroups
      (day 0, 21 and 42). Colostrum groups of mice were given a daily oral supplement
      of 50 mg/kg body weight of bovine colostrum and the exercise group of mice were
      made to exercise on the treadmill for 30 minutes per day. Total antioxidants,
      lipid hydroperoxides, xanthine oxidase and super oxide dismutase level was
      assayed from the homogenate of hind limb skeletal muscle. RESULTS: Exercise
      induced a significant oxidative stress in skeletal muscles as evidenced by the
      elevated lipid hydroperoxides and xanthine oxidase levels. There was a
      significant decrease in skeletal muscle total antioxidants and superoxide
      dismutase levels. Daily colostrum supplement significantly reduced the lipid
      hydroperoxides and xanthine oxidase enzyme level and increased the total
      antioxidant levels in the leg muscle. CONCLUSION: Thus, the findings of this
      study showed that daily bovine colostrum supplementation was beneficial to
      skeletal muscle to reduce the oxidant-induced damage during muscular exercise.

PMID- 23173927
TI  - Professional health care use and subjective unmet need for social or emotional
      problems: a cross-sectional survey of the married and divorced population of
      Flanders.
AB  - BACKGROUND: The high mental health care consumption rates of divorced singles may
      constitute a heavy burden on the public health care system. This raises the
      question of whether their higher health care use stems from a greater need, or
      whether there are other factors contributing to these high consumption rates. We
      examine both health care use and subjective unmet need (perceiving a need for
      care without seeking it) because of social or emotional problems of the divorced
      singles, the repartnered divorcees, and the married. Moreover, we investigate how
      health care use and subjective unmet need relate to each other. METHODS: We
      conduct several gender specific logistic regressions employing data from the
      Divorce in Flanders Survey (N men = 2884; N women = 3317). RESULTS: Results show
      that the divorced singles have more contact with professional health care
      providers (general practitioners, psychiatrists, and psychologists) because of
      social or emotional problems, and more often perceive unmet needs. The higher
      health care use rates and greater subjective unmet needs can largely be
      attributed to higher levels of depressive symptoms. Surprisingly, we find that
      non-frequent health care users more often perceive a subjective unmet need than
      frequent health care users and those who have not contacted any health care
      provider. CONCLUSION: The single divorced consult health care providers more
      often because of social or emotional problems and they also perceive unmet needs
      more often.

PMID- 23173928
TI  - Systemic analysis of inducible target of rapamycin mutants reveal a general
      metabolic switch controlling growth in Arabidopsis thaliana.
AB  - The target of rapamycin (TOR) pathway is a major regulator of growth in all
      eukaryotes, integrating energy, nutrient and stress signals into molecular
      decisions. By using large-scale MS-based metabolite profiling of primary,
      secondary and lipid compounds in combination with array-based transcript
      profiling, we show that the TOR protein not only regulates growth but also
      influences nutrient partitioning and central energy metabolism. The study was
      performed on plants exhibiting conditional down-regulation of AtTOR expression,
      revealing strong regulation of genes involved in pathways such as the cell cycle,
      cell-wall modifications and senescence, together with major changes in
      transcripts and metabolites of the primary and secondary metabolism. In agreement
      with these results, our morphological and metabolic analyses disclosed major
      metabolic changes leading to massive accumulations of storage lipids and starch.
      The implications of these data in the context of the general role of TOR in
      eukaryotic systems are discussed in parallel with the plant-specific aspects of
      TOR function. Finally, we propose a role for harnessing the plant TOR pathway by
      utilizing it as a potent metabolic switch, offering a possible route for
      biotechnological optimization of plant energy content and carbon partitioning for
      the production of bioenergy.

PMID- 23173929
TI  - A prospective experimental study of liver fibrosis with ultrasound and its
      correlation with hepatic reserve function and hemodynamics.
AB  - BACKGROUND: Progressive hepatic fibrosis is the eventual cause of liver
      cirrhosis. Doppler ultrasound has been used to detect hemodynamic changes that
      are known to be present during the pre-cirrhotic stages of hepatic fibrogenesis.
      However, the relationship between the Doppler ultrasound parameters and the
      impairment of the liver function has not been fully investigated. The purpose of
      this study was to explore the hepatic function reserve and its relationship with
      the hepatic hemodynamics in a rabbit model of liver fibrosis using Doppler
      ultrasound. METHODS: A prospective study was performed. Sixty healthy New Zealand
      rabbits were included in this study. Eleven of them served as controls and were
      normally fed and provided with water drink; the rest of 49 rabbits that served as
      fibrosis group were normally fed but provided with 1.2 g/L of thioacetamide to
      create liver fibrosis model. Doppler measurements were performed in the portal
      trunk, proper hepatic artery and proper splenic artery. The hepatic circulation
      index (HCI) was calculated. Hepatic function reverse was evaluated by measuring
      the indocyanine green clearance and retention rate at 15 min (ICG R15) test.
      Portal venous pressure (PVP) was measured using the portal vein punctuation
      equipment. RESULTS: HCI was significantly decreased and PVP increased in the
      advanced fibrotic stage (F4) compared to mild and moderate fibrotic stage (F1-3),
      respectively (p<0.05). PVP and ICG R15 in the fibrotic group were significantly
      higher than that in the control group (ICG: 0.209+/-0.086 vs. 0.093+/-0.023,
      p<0.01). Within the fibrotic groups, PVP was higher in advanced fibrotic stage
      (F4) than those in mild (F1-2) or moderate (F3) fibrotic stages (p<0.05). Both
      HCI and PVP correlated well with ICG R15 (r = -0.890, and r = 0.780, p <0.01).
      CONCLUSIONS: Hepatic function reserve closely relates to the hepatic hemodynamics
      in the rabbit model of liver fibrosis. Doppler Ultrasound could be reliably used
      to assess the hepatic function reserve and hemodynamic changes in different
      stages of liver fibrosis.

PMID- 23173930
TI  - Cutaneous tuberculosis in children.
AB  - Cutaneous tuberculosis is a rare form of extrapulmonary tuberculosis that
      accounts for 1% to 2% of cases. Childhood skin tuberculosis represents 18% to 82%
      of all cutaneous tuberculosis cases. Scrofuloderma and lupus vulgaris are the two
      most common clinical forms in children. An increase in the number of tuberculids,
      especially lichen scrofulosorum, has been observed in the last several years.
      Cutaneous tuberculosis in children can be severe and have a protracted course.
      Multiplicity of lesions and multifocal disseminated involvement in scrofuloderma
      and lupus vulgaris is common. Scrofuloderma progressing to gummatous lesions
      (scrofulous gumma) is mostly described in children. Morbidities and deformities
      are more severe in children.

PMID- 23173932
TI  - Abstracts of Sepsis 2012. Paris, France. November 14-16, 2012.

PMID- 23173931
TI  - Genetic manipulation of myoblasts and a novel primary myosatellite cell culture
      system: comparing and optimizing approaches.
AB  - The genetic manipulation of skeletal muscle cells in vitro is notoriously
      difficult, especially when using undifferentiated muscle cell lines (myoblasts)
      or primary muscle stem cells (myosatellites). We therefore optimized methods of
      gene transfer by overexpressing green fluorescent protein (GFP) in mouse C2C12
      cells and in a novel system, primary rainbow trout myosatellite cells. A common
      lipid-based transfection reagent was used (Lipofectamine 2000) along with three
      different viral vectors: adeno-associated virus serotype 2 (AAV2), baculovirus
      (BAC) and lentivirus. Maximal transfection efficiencies of 49% were obtained in
      C2C12 cells after optimizing cell density and reagent : DNA ratio, although the
      GFP signal rapidly dissipated with proliferation and was not maintained with
      differentiation. The transduction efficiency of AAV2 was optimized to 65% by
      extending incubation time and decreasing cell density, although only 30% of cells
      retained expression after passing. A viral comparison revealed that lentivirus
      was most efficient at transducing C2C12 myoblasts as 97% of cells were transduced
      with only 10(6) viral genomes (vg) compared to 54% with 10(8) vg AAV2 and 23%
      with 10(9) vg BAC. Lentivirus also transduced 90% of primary trout myosatellites
      compared to 1-10% with AAV2 and BAC. The phosphoglycerate kinase 1 (pgk) promoter
      was 10-fold more active than the cytomegalovirus immediate-early promoter in
      C2C12 cells and both were effective in trout myosatellites. Maximal transduction
      of C2C12 myotubes was achieved by differentiating myoblasts previously transduced
      with lentivirus and the pgk promoter. Thus, our optimized protocol proved highly
      effective in diverse muscle cell systems and could therefore help overcome a
      common technological barrier.

PMID- 23173933
TI  - Nectar regulation in Euphorbia tithymaloides L., a hummingbird-pollinated
      Euphorbiaceae.
AB  - Floral sexual phases can differ in nectar production and might be under selective
      pressure by pollinators. We studied Euphorbia tithymaloides, which has
      inflorescences that are initially female and then hermaphroditic. Volume and
      concentration of nectar were measured in both stages. Nectar production and the
      effect of extractions were determined using sets of bagged inflorescences;
      inflorescences in the hermaphroditic phase had higher values of nectar
      concentration, volume and sugar mass than inflorescences in the female phase.
      Nectar resorption was detected in senescent inflorescences. To test for
      homeostatic nectar regulation, artificial nectar was added and the response
      assessed after 24 h. The experiments showed that concentration and sugar mass are
      regulated within a narrow range, and the homeostatic points differ between the
      two sexual phases. These differences in nectar can be detected by hummingbirds,
      which prefer the female stage. Resorption and secretion seem to be part of a
      homeostatic mechanism by which nectar attributes are maintained to optimise sugar
      recovery.

PMID- 23173936
TI  - Gas-phase hydrosilylation of plasma-synthesized silicon nanocrystals with short-
      and long-chain alkynes.
AB  - Surface passivation of Si nanocrystals (NCs) is necessary to enable their
      utilization in novel photovoltaic and optoelectronic devices. Herein, we report
      the surface passivation of plasma-synthesized, H-terminated Si NCs via gas-phase
      hydrosilylation using a combination of short- and long-chain alkynes.
      Specifically, using in situ attenuated total reflection Fourier transform
      infrared spectroscopy, we show that a sequential exposure of the Si NC surface to
      acetylene and phenylacetylene results in a surface alkenyl coverage of ~58%,
      which is close to the theoretical maximum of ~55% and ~60% predicted for alkyl-
      and alkenyl-terminated Si(111) surfaces, respectively. We attribute this
      unprecedented high surface hydrocarbon coverage to the combination of short- and
      long-chain alkynes that reduce the steric hindrance on the surface, higher
      reactivity of 1-alkynes versus 1-alkenes of the same chain length, and the
      smaller van der Waals radius of the alkenyl groups compared to the alkyl groups.
      Unlike 1-alkenes, 1-alkynes also react with the surface to form the 1,1- and 1,2
      bridge structures via the bis-hydrosilylation reaction. However, our data clearly
      show that this reaction pathway cannot account for the enhanced surface coverage
      in the sequential exposure experiments, since exposure of the surface to just
      acetylene or phenylacetylene results in an almost identical surface coverage due
      to the 1,1- and 1,2-bridge sites.

PMID- 23173934
TI  - The Th2 cytokine, interleukin-4, abrogates the cohesion of normal stratum corneum
      in mice: implications for pathogenesis of atopic dermatitis.
AB  - There is mounting evidence that Th2 cytokines adversely affect skin barrier
      functions and contribute to the pathogenesis of atopic dermatitis (AD). AD is
      also characterized by abnormal cohesion in the stratum corneum (SC). However, the
      contribution of Th2 cytokines to this abnormality remains unknown. This study
      examined the effects of IL-4, a prototypic Th2 cytokine, on the cohesion of the
      SC. Structural and physiological assessments revealed that repeated intradermal
      injections of IL-4 compromised the cohesion of the SC of normal hairless mice.
      Two potential mechanisms were explored to account for the altered cohesion.
      First, IL-4 decreased the amount of corneodesmosomes and down-regulated the
      expression of desmoglein 1, but not of corneodesmosin (CDSN) or loricrin
      expression, in murine skin and in cultured human keratinocytes (KC). IL-4 did not
      affect the skin surface pH, and in situ zymography revealed no net change in
      total serine protease activity in the IL-4-treated SC. Yet, IL-4 enhanced
      expression of kallikrein (KLK)7, while simultaneously down-regulating KLK5 and
      KLK14. Finally, IL-4 did not alter the expression of the lympho-epithelial Kazal
      type inhibitor (LEKTI) in KC. This study suggests that IL-4 abrogates the
      cohesion of SC primarily by reducing epidermal differentiation.

PMID- 23173937
TI  - Detection of atrial fibrillation in the post-stroke setting: challenges and
      opportunities on the horizon.

PMID- 23173935
TI  - Specific antibody-dependent cellular cytotoxicity responses associated with slow
      progression of HIV infection.
AB  - Antibody-dependent cellular cytotoxicity (ADCC) is potentially an effective
      adaptive immune response to HIV infection. However, little is understood about
      the role of ADCC in controlling chronic infection in the small number of long
      term slow-progressors (LTSP) who maintain a relatively normal immunological state
      for prolonged periods of time. We analysed HIV-specific ADCC responses in sera
      from 139 HIV(+) subjects not on antiretroviral therapy. Sixty-five subjects were
      LTSP, who maintained a CD4 T-cell count > 500/MUl for over 8 years after
      infection without antiretroviral therapy and 74 were non-LTSP individuals. The
      ADCC responses were measured using an natural killer cell activation assay to
      overlapping HIV peptides that allowed us to map ADCC epitopes. We found that
      although the magnitude of ADCC responses in the LTSP cohort were not higher and
      did not correlate with CD4 T-cell depletion rates, the LTSP cohort had
      significantly broader ADCC responses compared with the non-LTSP cohort.
      Specifically, regulatory/accessory HIV-1 proteins were targeted more frequently
      by LTSP. Indeed, three particular ADCC epitopes within the Vpu protein of HIV
      were recognized only by LTSP individuals. Our study provides evidence that
      broader ADCC responses may play a role in long-term control of HIV progression
      and suggests novel vaccine targets.

PMID- 23173938
TI  - The effects of rear-wheel camber on the kinematics of upper extremity during
      wheelchair propulsion.
AB  - BACKGROUND: The rear-wheel camber, defined as the inclination of the rear wheels,
      is usually used in wheelchair sports, but it is becoming increasingly employed in
      daily propulsion. Although the rear-wheel camber can increase stability, it
      alters physiological performance during propulsion. The purpose of the study is
      to investigate the effects of rear-wheel cambers on temporal-spatial parameters,
      joint angles, and propulsion patterns. METHODS: Twelve inexperienced subjects
      (22.3+/-1.6 yr) participated in the study. None had musculoskeletal disorders in
      their upper extremities. An eight-camera motion capture system was used to
      collect the three-dimensional trajectory data of markers attached to the
      wheelchair-user system during propulsion. All participants propelled the same
      wheelchair, which had an instrumented wheel with cambers of 0 degrees , 9 degrees
      , and 15 degrees , respectively, at an average velocity of 1 m/s. RESULTS: The
      results show that the rear-wheel camber significantly affects the average
      acceleration, maximum end angle, trunk movement, elbow joint movement, wrist
      joint movement, and propulsion pattern. The effects are especially significant
      between 0 degrees  and 15 degrees . For a 15 degrees  camber, the average
      acceleration and joint peak angles significantly increased (p < 0.01). A single
      loop pattern (SLOP) was adopted by most of the subjects. CONCLUSIONS: The rear
      wheel camber affects propulsion patterns and joint range of motion. When choosing
      a wheelchair with camber adjustment, the increase of joint movements and the base
      of support should be taken into consideration.

PMID- 23173939
TI  - The effect of bariatric surgery in the difficult asthma-obesity phenotype: a case
      report.
AB  - INTRODUCTION: Obesity and asthma have become increasingly prevalent conditions in
      recent years; they often coexist and place a significant burden on the National
      Health Service. Asthma in the obese is more difficult to treat than in those with
      a normal body mass index (BMI) and is associated with resistance to traditional
      asthma therapies and increased use of healthcare resources. Weight loss can
      improve asthma control in such patients. The degree of weight loss achieved
      through dietary strategies, however, is often only modestly successful in this
      group. Bariatric surgery is increasingly used to achieve sustained significant
      weight loss in morbid obesity. It may offer under-recognized benefit in the
      difficult asthma-obesity phenotype. CASE STUDY: We describe the case of a 32-year
      old female with difficult asthma who had a BMI of 45 kg/m(2) at the time of
      referral to our clinic. Her asthma was uncontrolled despite maximal inhaled
      therapy, oral therapy with Zafirlukast, and daily high-dose (25 mg) oral
      prednisolone. Additional therapies (subcutaneous Terbutaline and the steroid
      sparing agent Methotrexate) had little impact on asthma control and she remained
      morbidly obese. She underwent gastric bypass surgery and, over the following 18
      months, her BMI dropped to 27.7 kg/m(2), her corticosteroid dose was reduced to
      7.5 mg (adrenal insufficiency proven), and maintenance inhaled therapy and oral
      medications were stopped as she maintained good asthma control. CONCLUSION: This
      case demonstrates the dramatic improvement that bariatric surgery can have on
      asthma symptoms and medication use in morbidly obese patients with very difficult
      to control asthma.

PMID- 23173940
TI  - The substrate specificity of the human ADP/ATP carrier AAC1.
AB  - The mitochondrial ADP/ATP carrier imports ADP from the cytosol into the
      mitochondrial matrix for its conversion to ATP by ATP synthase and exports ATP
      out of the mitochondrion to replenish the eukaryotic cell with chemical energy.
      Here the substrate specificity of the human mitochondrial ADP/ATP carrier AAC1
      was determined by two different approaches. In the first the protein was
      functionally expressed in Escherichia coli membranes as a fusion protein with
      maltose binding protein and the effect of excess of unlabeled compounds on the
      uptake of [(32)P]-ATP was measured. In the second approach the protein was
      expressed in the cytoplasmic membrane of Lactococcus lactis. The uptake of
      [(14)C]-ADP in whole cells was measured in the presence of excess of unlabeled
      compounds and in fused membrane vesicles loaded with unlabeled compounds to
      demonstrate their transport. A large number of nucleotides were tested, but only
      ADP and ATP are suitable substrates for human AAC1, demonstrating a very narrow
      specificity. Next we tried to understand the molecular basis of this specificity
      by carrying out molecular-dynamics simulations with selected nucleotides, which
      were placed at the entrance of the central cavity. The binding of the phosphate
      groups of guanine and adenine nucleotides is similar, yet there is a low
      probability for the base moiety to be bound, likely to be rooted in the greater
      polarity of guanine compared to adenine. AMP is unlikely to engage fully with all
      contact points of the substrate binding site, suggesting that it cannot trigger
      translocation.

PMID- 23173941
TI  - A novel method for efficient in vitro germination and tube growth of Arabidopsis
      thaliana pollen.
AB  - In addition to its importance in studies of plant reproduction and fertility,
      pollen is as widely employed as a model system of cell growth and development.
      This work demands robust, reproducible methods to induce pollen germination and
      morphologically normal growth of pollen tubes in vitro. Despite numerous
      advantages of Arabidopsis thaliana as a model plant, such experiments on pollen
      germination and pollen tube growth have often proved challenging. Our new method
      employs a physical cellulosic membrane, overlying an agarose substrate. By
      modulating the substrate composition, we provide important insights into the
      mechanisms promoting pollen growth both in vitro and in vivo. This effective new
      technical approach to A. thaliana pollen germination and tube growth results in
      swift, consistent and unprecedented levels of germination to over 90%. It can
      also promote rapid growth of long, morphologically normal pollen tubes. This
      technical development demonstrates that exogenous spermidine and a cellulosic
      substrate are key factors in stimulating germination. It has potential to greatly
      assist the study of reproduction in A. thaliana and its closest relatives, not
      only for the study of germination levels and pollen tube growth dynamics by
      microscopy, but also for biochemical and molecular analysis of germinating
      pollen.

PMID- 23173942
TI  - Abdominal aortic aneurysm in patients affected by intermittent claudication:
      prevalence and clinical predictors.
AB  - BACKGROUND: Abdominal aortic aneurysm (AAA) is a frequent cause of death among
      elderly. Patients affected by lower extremity peripheral arterial disease (LE
      PAD) seem to be particularly at high risk for AAA. We aimed this study at
      assessing the prevalence and the clinical predictors of the presence of AAA in a
      homogeneous cohort of LE-PAD patients affected by intermittent claudication.
      METHODS: We performed an abdominal ultrasound in 213 consecutive patients with
      documented LE-PAD (ankle/brachial index <= 0.90) attending our outpatient clinic
      for intermittent claudication. For each patient we registered cardiovascular risk
      factors and comorbidities, and measured neutrophil count. RESULTS: The ultrasound
      was inconclusive in 3 patients (1.4%), thus 210 patients (169 males, 41 females,
      mean age 65.9 +/- 9.8 yr) entered the study. Overall, AAA was present in 19
      patients (9.0%), with a not significant higher prevalence in men than in women
      (10.1% vs 4.9%, p = 0.300). Patients with AAA were older (71.2 +/- 7.0 vs 65.4 +/
      9.9 years, p = 0.015), were more likely to have hypertension (94.7% vs 71.2%, p
      = 0.027), and greater neutrophil count (5.5 [4.5 - 6.2] vs 4.1 [3.2 - 5.5] x
      10(3)/MUL, p = 0.010). Importantly, the c-statistic for neutrophil count (0.73,
      95% CI 0.60 - 0.86, p = 0.010) was higher than that for age (0.67, CI 0.56-0.78,
      p = 0.017). The prevalence of AAA in claudicant patients with a neutrophil count
      >= 5.1 x 10(3)/MUL (cut-off identified at ROC analysis) was as high as 29.0%.
      CONCLUSIONS: Prevalence of AAA in claudicant patients is much higher than that
      reported in the general population. Ultrasound screening should be considered in
      these patients, especially in those with an elevated neutrophil count.

PMID- 23173943
TI  - Feasibility of capsule endoscopy in elderly patients with obscure
      gastrointestinal bleeding. An up-to-date report.
AB  - BACKGROUND: Anemia is the most common hematologic abnormality in older
      populations. Furthermore, iron deficiency anemia is common and merits
      investigation and treatment, as it usually results from chronic occult bleeding
      from the gastrointestinal tract. In view of a wide use of capsule endoscopy as a
      diagnostic procedure for occult gastrointestinal bleeding and of the growth of
      aging population, we performed a literature review about the feasibility of
      capsule endoscopy in the elderly. METHODS: We conducted a literature search in
      the PubMed database in July 2012, and all English-language publications on
      capsule endoscopy in elderly patients since 2005 were retrieved. The potential
      original articles mainly focused on obscure gastrointestinal bleeding were all
      identified and full texts were obtained and reviewed for further hand data
      retrieving. RESULTS: We retrieved only six papers based on different primary end
      points. Four were retrospective non randomized studies and two were prospective
      non randomized studies. In the end 65, 70, 80 and 85 years were used as an age
      cut-off. All studies evaluate the diagnostic yield of capsule endoscopy in iron
      deficiency anemia. Only three studies assess the feasibility of capsule
      examination of the elderly. CONCLUSIONS: Iron deficiency anemia in the elderly
      with or without obscure gastrointestinal bleeding is the major indication for
      capsule endoscopy after a negative esophago-gastro-duodenoscopy and colonoscopy.
      It is safe and effective to identify a small bowel pathology without a great
      discomfort for the elderly. Inability to swallow the capsule, battery failure
      before capsule reaches the cecum, and capsule retention are some of the important
      problems associated with capsule endoscopy in elderly as well as in younger
      patients.

PMID- 23173944
TI  - Clinician's use of automated reports of estimated glomerular filtration rate: a
      qualitative study.
AB  - BACKGROUND: There is a growing awareness in primary care of the importance of
      identifying patients with chronic kidney disease (CKD) so that they can receive
      appropriate clinical care; one method that has been widely embraced is the use of
      automated reporting of estimated glomerular filtration rate (eGFR) by clinical
      laboratories. We undertook a qualitative study to examine how clinicians use eGFR
      in clinical decision making, patient communication issues, barriers to use of
      eGFR, and suggestions to improve the clinical usefulness of eGFR reports.
      METHODS: Our study used qualitative methods with structured interviews among
      primary care clinicians including both physicians and allied health providers,
      recruited from Kaiser Permanente Northwest, a non-profit health maintenance
      organization. RESULTS: We found that clinicians generally held favorable views
      toward eGFR reporting but did not use eGFR to replace serum creatinine in their
      clinical decision-making. Clinicians used eGFR as a tool to help identify CKD,
      educate patients about their kidney function and make treatment decisions.
      Barriers noted by several clinicians included a desire for greater education
      regarding care for patients with CKD and tools to facilitate discussion of eGFR
      findings with patients. CONCLUSIONS: The manner in which clinicians use eGFRs
      appears to be more complex than previously understood, and our study illustrates
      some of the efforts that might be usefully undertaken (e.g. specific clinician
      education) when encouraging further promulgation of eGFR reporting and usage.

PMID- 23173945
TI  - Does elastography reduce the need for thyroid FNAs?
AB  - OBJECTIVE: Ultrasound elastography (USE) assesses lesion stiffness by evaluating
      tissue distortion in response to stress; it is emerging as a potentially useful
      tool to augment the ultrasound characterisation of thyroid nodules. The aim of
      this study was to assess the accuracy of USE examination of thyroid nodules
      compared with pathological outcome, especially to determine whether USE could
      reliably detect benign nodules and reduce the numbers of ultrasound guided fine
      needle aspiration cytology (USgFNAC). DESIGN: Over a three-year period, thyroid
      nodules were initially characterised by B-mode ultrasound (US) findings. Where
      USgFNAC was indicated by clinical concern and/or the sonographic appearances, the
      lesion was then subjected to USE by an experienced operator prior to the USgFNAC.
      PATIENTS: 147 thyroid nodules were examined by USE and USgFNAC in 146 patients.
      MEASUREMENTS: The elastographic appearance was subjectively categorized at the
      time of the examination (soft, intermediate or hard) and subsequently compared
      with the cytological/histological outcome. RESULTS: A total of 122 nodules were
      non-neoplastic, 5 nodules were benign neoplasms, 10 nodules had indeterminate
      cytology and 10 were malignant neoplasms. The sensitivity of USE for malignancy
      was 90.0%, specificity was 79.6%, PPV was 24.3%, NPV was 99.1% and accuracy was
      80.3%. CONCLUSION: Thyroid nodules that are soft at USE have a high likelihood of
      being non-neoplastic and subjective USE assessment of thyroid nodules by an
      experienced operator can be a useful means of avoiding USgFNAC for benign
      nodules. In contrast, we suggest that all nodules that are intermediate or hard
      on USE undergo USgFNAC.

PMID- 23173946
TI  - DNA barcoding of Northern Nearctic Muscidae (Diptera) reveals high correspondence
      between morphological and molecular species limits.
AB  - BACKGROUND: Various methods have been proposed to assign unknown specimens to
      known species using their DNA barcodes, while others have focused on using
      genetic divergence thresholds to estimate "species" diversity for a taxon,
      without a well-developed taxonomy and/or an extensive reference library of DNA
      barcodes. The major goals of the present work were to: a) conduct the largest
      species-level barcoding study of the Muscidae to date and characterize the range
      of genetic divergence values in the northern Nearctic fauna; b) evaluate the
      correspondence between morphospecies and barcode groupings defined using both
      clustering-based and threshold-based approaches; and c) use the reference library
      produced to address taxonomic issues. RESULTS: Our data set included 1114
      individuals and their COI sequences (951 from Churchill, Manitoba), representing
      160 morphologically-determined species from 25 genera, covering 89% of the known
      fauna of Churchill and 23% of the Nearctic fauna. Following an iterative process
      through which all specimens belonging to taxa with anomalous divergence values
      and/or monophyly issues were re-examined, identity was modified for 9 taxa,
      including the reinstatement of Phaonia luteva (Walker) stat. nov. as a species
      distinct from Phaonia errans (Meigen). In the post-reassessment data set, no
      distinct gap was found between maximum pairwise intraspecific distances (range
      0.00-3.01%) and minimum interspecific distances (range: 0.77-11.33%).
      Nevertheless, using a clustering-based approach, all individuals within 98% of
      species grouped with their conspecifics with high (>95%) bootstrap support; in
      contrast, a maximum species discrimination rate of 90% was obtained at the
      optimal threshold of 1.2%. DNA barcoding enabled the determination of females
      from 5 ambiguous species pairs and confirmed that 16 morphospecies were
      genetically distinct from named taxa. There were morphological differences among
      all distinct genetic clusters; thus, no cases of cryptic species were detected.
      CONCLUSIONS: Our findings reveal the great utility of building a well-populated,
      species-level reference barcode database against which to compare unknowns. When
      such a library is unavailable, it is still possible to obtain a fairly accurate
      (within ~10%) rapid assessment of species richness based upon a barcode
      divergence threshold alone, but this approach is most accurate when the threshold
      is tuned to a particular taxon.

PMID- 23173947
TI  - When should a patient receive an arteriovenous graft rather than a fistula?
AB  - There has been a dramatic increase in the placement and use of arteriovenous
      fistulas (AVF) in US patients with chronic kidney disease over the past few
      years, in accordance with strong recommendations by Fistula First Initiative and
      KDOQI guidelines. However, AVF nonmaturation remains a substantial obstacle to
      achieving functional AVFs in a subset of patients, despite the widespread use of
      preoperative vascular mapping to assist surgeons in planning access surgery, and
      the growing use of interventions to salvage nonmaturing AVFs. In the right
      patient, aggressive efforts result in a functioning AVF, which provides adequate
      dialysis with relatively few interventions required to maintain its long-term
      patency for dialysis. In the wrong patient, aggressive efforts to achieve a
      mature AVF may result in numerous failed surgical and percutaneous procedures and
      prolonged catheter dependence, with all its associated complications. Thus,
      strict recommendations to place an AVF in all dialysis patients might not benefit
      every patient, and may actually harm some patients. There are no randomized
      clinical trials to address which patients are more suitable for placement of an
      arteriovenous graft (AVG), rather than an AVF. However, there is a wealth of
      observational studies, which taken cumulatively, may assist clinicians in
      identifying those patients who should receive an AVG. In this article, we review
      the relevant published literature regarding this topic and provide suggestions
      for stratifying patients who should receive each type of vascular access.

PMID- 23173948
TI  - Challenging the use of adult neuropsychological models for explaining
      neurodevelopmental disorders: developed versus developing brains.
AB  - In this paper, I contrast approaches from adult neuropsychology that seek
      selective, domain-specific deficits with approaches aimed at understanding the
      dynamics of developmental trajectories in children with genetic disorders. I
      stress the crucial difference between developed brains damaged in their mature
      state, and atypically developing brains. I also challenge the search for single
      genes to explain selective cognitive-level outcomes. Throughout, the paper argues
      that it is critical to trace cognitive-level deficits back to their basic-level
      processes in infancy, where genes are likely to exert their early influences, if
      we are to understand both the impairments and proficiencies displayed in children
      with neurodevelopmental disorders.

PMID- 23173949
TI  - Antioxidant activity and mechanism of Rhizoma Cimicifugae.
AB  - BACKGROUND: As a typical Chinese herbal medicine, rhizoma Cimicifugae (RC,   in
      Chinese) possesses various pharmacological effects involved in antioxidant
      activity. However, its antioxidant activity has not been reported so far. The aim
      of the present study was to systematically evaluate the antioxidant ability of RC
      in vitro, then discuss the mechanism. METHODS: Firstly, five RC extracts (i.e.
      petroleum ether extract PERC, ethyl acetate extract EARC, absolute ethanol
      extract AERC, 95% ethanol extract 95ERC, and water extract WRC) were prepared and
      determined by various antioxidant methods, including anti-lipidperoxidation,
      protection against DNA damage, .OH scavenging, .O2- scavenging, DPPH. (1,1
      diphenyl-2-picryl-hydrazl radical) scavenging, ABTS+. (2,2'-azino-bis (3
      ethylbenzo- thiazoline-6-sulfonic acid radical ion) scavenging, Cu2+-chelating,
      and Fe3+ reducing assays. Subsequently, we measured the chemical contents of five
      RC extracts, including total phenolics, total saponins, total sugars, caffeic
      acid, ferulic acid and isoferulic acid. Finally, we quantitatively analyzed the
      correlations between antioxidant levels (1/IC50 values) and chemical contents.
      RESULTS: In the study, the antioxidant levels and chemical contents (including
      total phenolics, total saponins, total sugars, caffeic acid, ferulic acid and
      isoferulic acid) of five RC extracts were determined by various methods. In all
      antioxidant assays, five RC extracts increased the antioxidant levels in a dose
      dependent manner. However, their antioxidant levels (IC50 values) and chemical
      contents significantly differed from each other. Quantitative analysis of the
      correlation showed that total phenolic was of significant positive correlations
      (average R value was 0.56) with antioxidant levels; In contrast, total sugars and
      total saponins had no positive correlation with antioxidant (the average R values
      were -0.20 and -0.26, for total sugars and total saponins, respectively); Among
      total phenolics, three phenolic acids (caffeic acid, ferulic acid and isoferulic
      acid) also displayed positive correlations (the average R values were 0.51, 0.50,
      and 0.51, for caffeic acid, ferulic acid and isoferulic acid, respectively).
      CONCLUSIONS: As an effective antioxidant, Rhizoma Cimicifugae can protect DNA and
      lipids against oxidative damage. Its antioxidant ability can be responsible for
      its various pharmacological effects and may be mainly attributed to the existence
      of total phenolics, among which caffeic acid, ferulic acid and isoferulic acid
      are regarded as main bioactive components. Rhizoma Cimicifugae exerts its
      antioxidant effect through metal-chelating, and radical-scavenging which is via
      donating hydrogen atom (H.) and donating electron (e).

PMID- 23173950
TI  - An UPLC-MS/MS method for highly sensitive high-throughput analysis of
      phytohormones in plant tissues.
AB  - BACKGROUND: Phytohormones are the key metabolites participating in the
      regulation of multiple functions of plant organism. Among them, jasmonates, as
      well as abscisic and salicylic acids are responsible for triggering and
      modulating plant reactions targeted against pathogens and herbivores, as well as
      resistance to abiotic stress (drought, UV-irradiation and mechanical wounding).
      These factors induce dramatic changes in phytohormone biosynthesis and transport
      leading to rapid local and systemic stress responses. Understanding of underlying
      mechanisms is of principle interest for scientists working in various areas of
      plant biology. However, highly sensitive, precise and high-throughput methods for
      quantification of these phytohormones in small samples of plant tissues are still
      missing. RESULTS: Here we present an LC-MS/MS method for fast and highly
      sensitive determination of jasmonates, abscisic and salicylic acids. A single
      step sample preparation procedure based on mixed-mode solid phase extraction was
      efficiently combined with essential improvements in mobile phase composition
      yielding higher efficiency of chromatographic separation and MS-sensitivity. This
      strategy resulted in dramatic increase in overall sensitivity, allowing
      successful determination of phytohormones in small (less than 50 mg of fresh
      weight) tissue samples. The method was completely validated in terms of analyte
      recovery, sensitivity, linearity and precision. Additionally, it was cross
      validated with a well-established GC-MS-based procedure and its applicability to
      a variety of plant species and organs was verified. CONCLUSION: The method can be
      applied for the analyses of target phytohormones in small tissue samples obtained
      from any plant species and/or plant part relying on any commercially available
      (even less sensitive) tandem mass spectrometry instrumentation.

PMID- 23173951
TI  - Schirmer tear test type I readings and intraocular pressure values assessed by
      applanation tonometry (Tonopen(r) XL) in normal eyes of four European species of
      birds of prey.
AB  - OBJECTIVE: To determine normal values for Schirmer tear test I and intraocular
      pressure in four European species of birds of prey. ANIMALS STUDIED: Twenty birds
      from each of the following species: Eurasian Tawny owl (Strix aluco), Little owl
      (Athene noctua), Common buzzard (Buteo buteo), and European kestrel (Falco
      tinnunculus). PROCEDURES: Both eyes of all birds (80 eyes) underwent a complete
      ophthalmic examination, which included a Schirmer tear test type I (STT-I)
      performed with commercially available strips and the assessment of the
      intraocular pressure (IOP) by applanation tonometry, employing the Tonopen
      XL((r)) device. The animals, which had been taken to a rescue center, were
      examined for ocular lesions prior to their eventual release into the wild. STT-I
      readings and IOP values were expressed as means +/- standard deviation. RESULTS:
      Schirmer tear test type I readings were as follows: Eurasian Tawny owls: 3.12 +/-
      1.92 mm/min; Little owls: 3.5 +/- 1.96 mm/min; Common buzzards: 12.47 +/- 2.66
      mm/min; European kestrels: 6.20 +/- 3.67 mm/min. IOP values were as follows:
      Eurasian Tawny owls: 11.21 +/- 3.12 mmHg; Little owls: 9.83 +/- 3.41 mmHg; Common
      buzzards: 17.2 +/- 3.53 mmHg; European kestrels: 8.53 +/- 1.59 mmHg. CONCLUSIONS:
      The results of this study give representative values for STT-I and IOP in four of
      the most common species of birds of prey in Europe.

PMID- 23173952
TI  - Electron transport in a GaPSb film.
AB  - We have performed transport measurements on a gallium phosphide antimonide
      (GaPSb) film grown on GaAs. At low temperatures (T), transport is governed by
      three-dimensional Mott variable range hopping (VRH) due to strong localization.
      Therefore, electron-electron interactions are not significant in GaPSb. With
      increasing T, the coexistence of VRH conduction and the activated behavior with a
      gap of 20 meV is found. The fact that the measured gap is comparable to the
      thermal broadening at room temperature (approximately 25 meV) demonstrates that
      electrons can be thermally activated in an intrinsic GaPSb film. Moreover, the
      observed carrier density dependence on temperature also supports the coexistence
      of VRH and the activated behavior. It is shown that the carriers are delocalized
      either with increasing temperature or magnetic field in GaPSb. Our new
      experimental results provide important information regarding GaPSb which may well
      lay the foundation for possible GaPSb-based device applications such as in high
      electron-mobility transistor and heterojunction bipolar transistors.

PMID- 23173953
TI  - Clinicians' experiences of becoming a clinical manager: a qualitative study.
AB  - BACKGROUND: There has been an increased interest in recruiting health
      professionals with a clinical background to management positions in health care.
      We know little about the factors that influence individuals' decisions to engage
      in management. The aim of this study is to explore clinicians' journeys towards
      management positions in hospitals, in order to identify potential drivers and
      barriers to management recruitment and development. METHODS: We did a qualitative
      study which included in-depth interviews with 30 clinicians in middle and first
      line management positions in Norwegian hospitals. In addition, participant
      observation was conducted with 20 of the participants. The informants were
      recruited from medical and surgical departments, and most had professional
      backgrounds as medical doctors or nurses. Interviews were analyzed by systemic
      text condensation. RESULTS: We found that there were three phases in clinicians'
      journey into management; the development of leadership awareness, taking on the
      manager role and the experience of entering management. Participants' experiences
      suggest that there are different journeys into management, in which both external
      and internal pressure emerged as a recurrent theme. They had not anticipated a
      career in clinical management, and experienced that they had been persuaded to
      take the position. Being thrown into the position, without being sufficiently
      prepared for the task, was a common experience among participants. Being left to
      themselves, they had to learn management "on the fly". Some were frustrated in
      their role due to increasing administrative workloads, without being able to
      delegate work effectively. CONCLUSIONS: Path dependency and social pressure seems
      to influence clinicians' decisions to enter into management positions. Hospital
      organizations should formalize pathways into management, in order to identify,
      attract, and retain the most qualified talents. Top managers should make sure
      that necessary support functions are available locally, especially for early
      stage clinician managers.

PMID- 23173954
TI  - Behavioural inventory of the giraffe (Giraffa camelopardalis).
AB  - BACKGROUND: Numerous factors like continuous habitat reduction or fragmentation
      for free-ranging giraffes (Giraffa camelopardalis) as well as e.g. suboptimal
      housing conditions for animals in captivity might lead to behavioural alterations
      as part of the overall adaptation process to the changing living conditions. In
      order to facilitate current and future studies on giraffe behaviour, a
      comprehensive ethogram was compiled based on existing literature, as well as
      observations on giraffes in the wild (Hwange National Park, Zimbabwe; Entabeni
      Game Reserve, South Africa), and in captivity (National Zoological Gardens of
      South Africa, Pretoria). FINDINGS: The resulting ethogram lists 65 different
      behavioural patterns, which were described and grouped into seven categories:
      General activities, Abnormal repetitive behaviours, General interactions, Bull
      Cow behaviour, Bull-Bull behaviour, Cow-Bull behaviour, Maternal behaviours, and
      Interactions by calves. The behaviours were further described regarding a
      presumed purpose, particularly with respect to social interactions and sexual
      behaviour. Contradictory descriptions from previous studies were considered and
      discussed in comparison with our own observations. CONCLUSIONS: This ethogram
      provides a basis for current and future studies by suggesting a terminology which
      can be used for harmonizing behavioural observations, thus helping to facilitate
      comparability of future results. Subsequently, a better understanding of the
      behavioural ecology of giraffes in the wild as well as in captivity could aid
      future conservation efforts.

PMID- 23173955
TI  - Editorial: possible therapeutic targets for the treatment of diabetic
      retinopathy: evidences from experimental models.

PMID- 23173956
TI  - The concomitance of hypertension and diabetes exacerbating retinopathy: the role
      of inflammation and oxidative stress.
AB  - Diabetes and hypertension frequently coexist and constitute the most notorious
      combination for the pathogenesis of DR. Large clinical trials have clearly
      demonstrated that tight control of glycaemia and/or blood pressure significantly
      reduces the incidence and progression of DR. The mechanism by which hypertension
      interacts with diabetes to exacerbate the retinal disease is not completely
      understood. From experimental studies, increasing evidence demonstrates that
      chronic inflammation and oxidative stress are involved. In the present review, we
      summarize data obtained from our research along with those from other groups to
      better understand the role of hypertension in the pathogenesis of DR. It is
      suggested that oxidative stress and inflammation may be common denominators of
      retinal damage in the presence of hypertension in diabetic patients. 

PMID- 23173957
TI  - The renin-angiotensin system and advanced glycation end-products in diabetic
      retinopathy: impacts and synergies.
AB  - Diabetic retinopathy is a major cause of vision impairment and blindness and
      represents a significant health burden throughout the world. There is
      considerable interest in developing new treatments that retard the progression of
      diabetic retinopathy from its early to proliferative stages. It could be argued
      that the absence of an ideal therapy for diabetic retinopathy comes from an
      incomplete understanding about the biochemical mechanisms that underlie this
      disease, and their precise impact on specific retinal cell populations. Findings
      from pre-clinical and clinical studies indicate that both the renin-angiotensin
      system (RAS) and advanced glycation end-products (AGEs) influence various aspects
      of diabetic retinopathy. Of interest is growing evidence of cross-talk between
      the RAS and AGEs pathways. This review will discuss the role of both the RAS and
      AGEs in diabetic retinopathy, and how the identification of interactions between
      the two pathways may have implications for the development of new treatment
      strategies. 

PMID- 23173958
TI  - Mitochondrial dysfunction and endoplasmic reticulum stress in diabetic
      retinopathy: mechanistic insights into high glucose-induced retinal cell death.
AB  - Hyperglycemia, a prominent characteristic of diabetes, has been implicated in the
      apoptotic death of vascular and neuronal cells in the retina. In diabetic
      retinopathy, mitochondrial dysfunction, endoplasmic reticulum (ER) stress, and
      subsequent breakdown of cellular homeostasis play a critical role in retinal cell
      death. In particular, changes in mitochondrial morphology, mitochondrial membrane
      potential heterogeneity, oxygen consumption rate and protein misfolding are
      beginning to be recognized as key players in the demise of retinal vascular cells
      in diabetes. Some of these key changes contribute to oxidative stress and
      influence ion transport, impacting overall cellular homeostasis. The primary
      objective of this review is to provide insight into the mechanisms in which high
      glucose influences two disparate cellular organelles, mitochondria and ER, in
      promoting apoptotic demise of retinal vascular and neuronal cells in diabetic
      retinopathy. 

PMID- 23173959
TI  - Poor response to antiplatelet drugs. An important issue in drug-eluting stents.
AB  - Platelet aggregation activity is the cornerstone of the pathogenesis of
      atherothrombosis and plays a main role in the appearance of major adverse cardiac
      events (MACE). This aspect has become even more important nowadays due to the use
      of drug-eluting stents (DES), where a proper platelet inhibition is required.
      Dual antiplatelet therapy with aspirin and clopidogrel in patients undergoing
      percutaneous coronary intervention (PCI) has widely demonstrated its beneficial
      effect in reducing MACE compared with aspirin alone. These benefits had also been
      established in short and long term treatment in patients with coronary artery
      disease managed with a conservative strategy. However, despite dual antiplatelet
      therapy an important number of patients experience new MACE related to an
      incomplete platelet inhibition that can be caused by the interaction of different
      mechanisms, not fully known at the moment. Several clinical studies suggested the
      significant variability in individual patient response to antiplatelet drugs to
      be due to the use of different laboratory tests. Moreover, other studies
      associated the low responsiveness status with an increased risk of recurrent
      cardiovascular events. Notably, resistance or reduced response to antiplatelet
      therapy with aspirin and clopidogrel is a clinically relevant entity that needs
      to be taken into account in order to perform a proper and individualized
      treatment strategy. Recent antiplatelet drugs such as prasugrel and ticagrelor
      have appeared to be an attractive option for patients with resistance or low
      response to traditional therapy. In this article we review aspirin and
      clopidogrel resistance as a clinical entity, the different mechanisms that could
      be linked to treatment failure, its relation with special situations and future
      perspectives in this area. 

PMID- 23173960
TI  - Editorial (hot topic: renal sympathetic denervation and cardiovascular disease:
      past, present and future).

PMID- 23173961
TI  - Clinical studies of renal nerve ablation. Unanswered questions for its efficacy
      and safety.
AB  - Resistant hypertension is frequently encountered and remains challenging in
      everyday clinical practice despite the availability of numerous effective
      antihypertensive drugs. Existing limitations in drug therapy renders renal nerve
      ablation (RNA) an attractive alternative for the management of resistant
      hypertension. RNA has been proven so far both effective and safe in small
      clinical studies. However, every novel technique raises several questions that
      need to be answered before the wide application of this approach. Likewise,
      existing data with RNA leave some unanswered questions, which among others
      include: the heterogeneity in blood pressure response, the identification of
      response predictors, the extent of RNA, the association between office and
      ambulatory blood pressure reduction, the long-term efficacy and safety of the
      procedure, the time-course of blood pressure response, and the effects on renal
      function in the long-term. This review aims to discuss these issues since RNA
      represents one of the hottest topics in hypertension and research directions are
      urgently needed. 

PMID- 23173962
TI  - The role of sympathetic nervous system in the progression of chronic kidney
      disease in the era of catheter based sympathetic renal denervation.
AB  - The kidney has been shown to be critically involved as both trigger and target of
      sympathetic nervous system overactivity in both experimental and clinical
      studies. Renal injury and ischemia, activation of renin angiotensin system and
      dysfunction of nitric oxide system have been implicated in adrenergic activation
      from kidney. Conversely, several lines of evidence suggest that sympathetic
      overactivity, through functional and morphological alterations in renal
      physiology and structure, may contribute to kidney injury and chronic kidney
      disease progression. Pharmacologic modulation of sympathetic nervous system
      activity has been found to have a blood pressure independent renoprotective
      effect. The inadequate normalization of sympathoexcitation by pharmacologic
      treatment asks for novel treatment options. Catheter based renal denervation
      targets selectively both efferent and afferent renal nerves and functionally
      denervates the kidney providing blood pressure reduction in clinical trials and
      renoprotection in experimental models by ameliorating the effects of excessive
      renal sympathetic drive. This review will focus on the role of sympathetic
      overactivity in the pathogenesis of kidney injury and CKD progression and will
      speculate on the effect of renal denervation to these conditions. 

PMID- 23173963
TI  - How to assess sympathetic nervous system activity in clinical practice.
AB  - The present paper reviews the techniques allowing to assess sympathetic activity
      in humans, highlighting their advantages and limitations. While plasma
      noradrenaline measurement represents a useful and widely used method to evaluate
      sympathetic neural function, new approaches, developed starting from the
      seventies, like direct recording of sympathetic nerve traffic and noradrenaline
      spillover. These approaches have largely supplanted the plasma noradrenaline
      approach due to the precise estimation of the behavior of regional sympathetic
      neural function. The paper in particular will focus the microneurographic
      technique, considered as the gold standard, and on the new clinical evidences
      obtained with this technique. 

PMID- 23173964
TI  - Renal sympathetic denervation and renal physiology.
AB  - The sympathetic nervous system has a profound effect on the kidney's ability to
      regulate blood pressure and, vice versa, the kidney has an important effect on
      the overall sympathetic tone. As a result, renal sympathetic nerves are crucial
      for initiation and the maintenance of systemic hypertension. It is fairly well
      established that efferent renal sympathetic nerve activity contributes
      significantly to homeostatic regulation of renal blood flow, glomerular
      filtration rate, renal tubular epithelial cell solute and water transport, and
      hormonal release. The afferent nerves from the kidney activate central
      sympathetic nervous system activity, participate in a reflex control system via
      reno-renal reflexes and are involved in cardiovascular regulation and
      pathogenesis of hypertension in CKD patients whose kidney ischemia also seems to
      play a key role. Sympathetic nerve modulation in hypertension had been considered
      as a therapeutic strategy long before the advent of modern pharmacological
      therapies. Renal sympathetic denervation with a percutaneous, catheter-based
      approach results in significant and sustained blood pressure reduction in
      patients with resistant hypertension. This procedure has also beneficial effects
      in multiple organs function. However, renal physiology and the long term observed
      benefits with the use of renal sympathetic denervation have not completely
      elucidated. 

PMID- 23173965
TI  - Metabolic effects of renal denervation.
AB  - In the present review article we address the issue of the potential effect of
      renal sympathetic denervation (RSD) on metabolic states associated with resistant
      hypertension. So far, there is an established pathophysiological background
      denoting that abnormalities in glucose metabolism especially in obese patients
      and in those with sleep apnea are constantly accompanied by increased sympathetic
      firing, as assessed by markers of sympathetic activity. Since resistant
      hypertension is also characterized by enhanced sympathetic activity, it seems
      logical and biologically plausible, that RSD might favorably influence impaired
      glucose metabolism, sleep disorders and increased body adiposity beyond BP
      lowering. Despite the limited evidence from clinical trials, there are promising
      data suggesting that RSD indeed ameliorates glucose metabolism-related measures
      in resistant hypertension. Well-designed randomized trials recruiting a larger
      number of patients with hypertension, and focused on metabolic parameters, may
      refine the role of RSD as a potential intervention to treat dysmetabolic states
      associated with hypertension. 

PMID- 23173966
TI  - Peri-procedural care of renal nerve ablation candidates.
AB  - Percutaneous catheter-based transluminal renal nerve ablation (RNA) by delivery
      of radiofrequency energy constitutes a novel therapeutic strategy for the
      treatment of resistant hypertension. The sympathetic nervous activation to the
      kidney and the sensory afferent signals to the central nervous system represent
      the targets of RNA. In this review we summarize current recommendations for
      appropriate patient selection for RNA and multimodal strategies in order to
      optimize pharmacological treatment for resistant hypertension. The safety and
      efficacy of the RNA based on published trials are also presented. Furthermore, a
      detailed description of the periprocedural management, the methodology of the RNA
      procedure and appropriate follow-up are provided. In conclusion, in order to
      improve the overall clinical outcome and achieve optimal management of resistant
      hypertensive patients before and after the RNA, experienced and certified centers
      are of major importance. 

PMID- 23173967
TI  - Development of natural products as anti-parasitic agents.
AB  - Parasites are eukaryotic pathogens and largely include protozoa, helminths and
      arthropods that cause different diseases to human. Parasitic diseases have a
      significant impact on developing countries and it has raised the mortality rate
      to various millions per year. Despite the recent progress, no vaccines are
      presently available against any of the major parasitic infections of humans.
      Chemotherapy remains the only option for both clinical and control management.
      However, conventional drugs are present with features that limit their utility,
      such as high cost, poor compliance, drug resistance, low efficacy and poor
      safety. There is thus a clear need for new therapeutic agents against parasites
      infections. 

PMID- 23173968
TI  - Plants used in traditional medicine: extracts and secondary metabolites
      exhibiting antileishmanial activity.
AB  - Plants and their extracts have been used traditionally against different
      pathologies, and in some poor regions they are the only therapeutic source for
      treatments. Moreover, the identification of specific active secondary metabolites
      can be account for amelioration of clinical status of suffering individual. A
      series of ethnopharmacological surveys conducted in Brazil recorded the
      traditional use of plants against different pathologies and interestingly, some
      of them presented antileishmanial activity in vitro and in vivo, possibly due to
      their immunostimulatory, healing and microbicidal properties. Of note, Leishmania
      parasites can alter patient's immunological status, leading to the development of
      extensive skin and/or visceral alterations. Therefore, the extracts or secondary
      metabolites presented in plants that might be capable of improving the
      pathological conditions can be attractive candidates in the development of new
      chemotherapeuticals against leishmaniosis. 

PMID- 23173969
TI  - An in-silico investigation of anti-Chagas phytochemicals.
AB  - Over 18 million people in tropical and subtropical America are afflicted by
      American trypanosomiasis or Chagas disease. In humans, symptoms of the disease
      include fever, swelling, and heart and brain damage, usually leading to death.
      There is currently no effective treatment for this disease. Plant products
      continue to be rich sources of clinically useful drugs, and the biodiversity of
      the Neotropics suggests great phytomedicinal potential. Screening programs have
      revealed numerous plant species and phytochemical agents that have shown in-vitro
      or in-vivo antitrypanosomal activity, but the biochemical targets of these
      phytochemicals are not known. In this work, we present a molecular docking
      analysis of Neotropical phytochemicals, which have already demonstrated
      antiparasitic activity against Trypanosoma cruzi, with potential druggable
      protein targets of the parasite. Several protein targets showed in-silico
      selectivity for trypanocidal phytochemicals, including trypanothione reductase,
      pteridine reductase 2, lipoamide dehydrogenase, glucokinase, dihydroorotate
      dehydrogenase, cruzain, dihydrofolate-reductase/thymidylate-synthase, and
      farnesyl diphosphate synthase. Some of the phytochemical ligands showed notable
      docking preference for trypanothione reductase, including flavonoids, fatty-acid
      derived oxygenated hydrocarbons, geranylgeraniol and the lignans ganschisandrine
      and eupomatenoid-6. 

PMID- 23173970
TI  - Marine products with anti-protozoal activity: a review.
AB  - The marine organisms are a rich source of varied natural products with unique
      functionality. A variety of natural products of new molecular structures with
      diverse biological activities have been reported from marine flora and fauna for
      treatment and/or prevention of human diseases. The present review briefly
      illustrates current status of marine products as antiprotozoal agents. The in
      vitro and in vivo studies of marine algae, invertebrates and micro-organism
      against different protozoa parasites are included. The marine products studied,
      according to international criterions for selection of more promisory products in
      the different models reported, demonstrated their potentialities as antiprozoal
      agents. Herein, the interest of scientific community to search new alternatives
      from marine environment has been demonstrated. 

PMID- 23173971
TI  - In-vivo and In-vitro activities of medicinal plants on ecto, endo and
      haemoparasitic infections: a review.
AB  - Crude methanol, pet. ether, ethyl acetate, n-hexane, dichloromethane and aqueous
      extracts of various species of medicinal plants have shown significant in-vivo
      and in-vitro pharmacological activities against ecto, endo and haemoparasites.
      The scientific evaluations of the use of the plants as antiparasitic agents were
      based on the claims of folklore drawn from traditional healers from various
      communities across the world. The pharmacological activities of these plants were
      associated with the presence of various bioactive compounds such as alkaloids,
      flavonoids, saponins, glycosides, allicinine, harmala, harmaline, harman,
      tetrahydroharman, ursolic acid, terapines, tannins, phenolic compounds, embelin
      and brucine. These compounds were either found in the leaves, seeds, bulbs,
      flowers, stem, root barks or entire plant. In the in-vivo studies, plant extracts
      were tested using animal models such as mice, sheep, goats, cattle and dogs. The
      in-vivo anthelmintic activities of the plants were assessed by faecal egg out
      puts and post-mortem worm counts which in most instances achieved 70-90% priori
      levels with some of the plants. For haemoparasitic infections, parasitaemia
      clearance levels were used, while larvae and adult deaths were used to measure
      the activity of the plants against ectoparasites. For in-vitro activities,
      inhibitory concentration IC50 values using the brine lethality test, micro
      dilution, flow cytometery and larval packet test were used to assess the efficacy
      of the plant extracts on the parasites in various cell cultures. Significant in
      vitro activity of 99.8% at 3.1mg/ml was achieved with the ethanolic extract of
      Azadirachta indica. Many of the plants were found to be more potent and possessed
      similar mechanism of action as their novel synthetic drugs. Such breakthroughs
      have led to the development of less toxic, cheaper and readily available drugs.
      Worthy of note is the use of the fruit of the Thai plant Piper longum
      (PIPERACEAE) as part of a drug formulation used in India for the treatment of
      clinical giardiosis in human patients. 

PMID- 23173972
TI  - Setting a colorimetric assay with MTT for assessment of trichomonicidal activity.
AB  - Trichomonas vaginalis infection is associated with important problems of public
      health, including the spreading of other sexual transmitted infections. The
      existence of clinical resistant isolates metronidazole and tinidazole, the drugs
      approved for the treatment of trichomoniasis, points to the necessity of continue
      searching for trichomonicidal substances. Here we optimize a colorimetric assay
      with MTT to assess trichomonas viability. The absence of ascorbic acid and
      cysteine in the culture medium was indispensable to perform the assay, as these
      compounds spontaneously reduce the MTT. Linearity of absorbance was verified
      versus trichomonas counts. Medium inhibitory concentration of metronidazole was
      determined using the sigmoidal Emax model, by comparing the absorbance of test
      cultures with controls. The obtained value was in the range of published data.
      The test would be used for the evaluation of trichomonicidal activity of chemical
      compounds and natural products. 

PMID- 23173973
TI  - Insulin resistance: a risk marker for disease and disability in the older person.
AB  - Clinical metabolic studies have demonstrated that insulin action declines
      progressively with age in humans. In addition to its close association with Type
      2 diabetes, which reduces life expectancy in older people, age-related insulin
      resistance is implicated in pathogenesis of several highly prevalent disorders
      for which ageing is a major risk factor. These include atherosclerotic
      cardiovascular disease, dementia, frailty and cancer. Accordingly, insulin
      resistance may be viewed as biomarker of age-related ill health and reduced
      lifespan. The rapidly rising number of older people, coupled with a high
      prevalence of insulin resistance resulting from obesity and sedentary lifestyles,
      presents unprecedented public health and societal challenges. Studies of
      centenarians have shown that preserved whole-body sensitivity to insulin is
      associated with longevity. The mechanisms through which insulin action is
      associated with age-related diseases remain unclear. Changes in body composition,
      i.e. sarcopenia and excess adiposity, may be more potent than age per se.
      Moreover, the impact of insulin resistance has been difficult to disentangle from
      the clustering of vascular risk factors that co-segregate with the insulin
      resistance-hyperinsulinaemia complex. Potentially modifiable mediators of age
      related changes in insulin sensitivity include alterations in adipocytokines,
      impaired skeletal myocyte mitochondrial function and brown fat activity. The
      hypothesis that improving or maintaining insulin sensitivity preserves health and
      extends lifespan merits further evaluation. Practical non-pharmacological
      interventions directed against age-related insulin resistance remain
      underdeveloped. Novel metabolically active pharmacological agents with
      theoretical implications for some age-related disorders are entering clinical
      trials. However, recent adverse experiences with the thiazolidinediones suggest
      the need for a cautious approach to the use of insulin sensitizing drugs in older
      people. This could be particularly important in the absence of diabetes where the
      risk to benefit analysis may be less favourable.

PMID- 23173974
TI  - Abstracts of the British Society of Breast Radiology Annual Scientific Meeting
      2012. Leeds, United Kingdom. November 12-13, 2012.

PMID- 23173975
TI  - The biological fate of silver ions following the use of silver-containing wound
      care products - a review.
AB  - Ionic silver has a long history as an antimicrobial in human health care. This
      article is a review of the published literature on how ionic silver may enter the
      body from exposure to silver-containing wound care products and its eventual
      metabolic fates, in an assessment of the safety during normal use of these
      products in wound care. Following the application to breached skin, there appears
      to be little evidence of localised or systemic toxicity, and this is borne out by
      the continuous use of silver sulfadiazine formulations for more than 50 years.
      Consequently, following normal use, the risk of silver ion toxicity locally and
      systemically is considered to be low or negligible. 

PMID- 23173976
TI  - A role for the miR396/GRF network in specification of organ type during flower
      development, as supported by ectopic expression of Populus trichocarpa miR396c in
      transgenic tobacco.
AB  - The MIR396 family, composed of ath-miR396a and ath-miR396b in Arabidopsis, is
      conserved among plant species and is known to target the Growth-Regulating Factor
      (GRF) gene family. ath-miR396 overexpressors or grf mutants are characterised by
      small and narrow leaves and show embryogenic defects such as cotyledon fusion.
      Heterologous expression of ath-miR396a has been reported in tobacco and resulted
      in reduction of the expression of three NtGRF genes. In this study, the precursor
      of the Populus trichocarpa ptc-miR396c, with a mature sequence identical to ath
      miR396b, was expressed under control of the CaMV35S promoter in tobacco. Typical
      phenotypes of GRF down-regulation were observed, including cotyledon fusion and
      lack of shoot apical meristem (SAM). At later stage of growth, transgenic plants
      had delayed development and altered specification of organ type during flower
      development. The third and fourth whorls of floral organs were modified into
      stigmatoid anthers and fasciated carpels, respectively. Several NtGRF genes
      containing a miR396 binding site were found to be down-regulated, and the
      cleavage of their corresponding mRNA at the miR396 binding site was confirmed for
      two of them using RACE-PCR analysis. The data obtained agree with the functional
      conservation of the miR396 family in plants and suggest a role for the miR396/GRF
      network in determination of floral organ specification. 

PMID- 23173977
TI  - The colloidal state of tannins impacts the nature of their interaction with
      proteins: the case of salivary proline-rich protein/procyanidins binding.
AB  - While the definition of tannins has been historically associated with its
      propensity to bind proteins in a nonspecific way, it is now admitted that
      specific interaction also occurs. The case of the astringency perception is a
      good example to illustrate this phenomenon: astringency is commonly described as
      a tactile sensation induced by the precipitation of a complex composed of proline
      rich proteins present in the human saliva and tannins present in beverages such
      as tea or red wines. In the present work, the interactions between a human saliva
      protein segment and three different procyanidins (B1, B3, and C2) were
      investigated at the atomic level by NMR and molecular dynamics. The data provided
      evidence for (i) an increase in affinity compared to shortest human saliva
      peptides, which is accounted for by protein "wraping around" the tannin, (ii) a
      specificity in the interaction below tannin critical micelle concentration (CMC)
      of ca. 10 mM, with an affinity scale such that C2 > B1 > B3, and (iii) a
      nonspecific binding above tannin CMC that conducts irremediably to the
      precipitation of the tannins/protein complex. Such physicochemical findings
      describe in accurate terms saliva protein-tannin interactions and provide support
      for a more subtle description by oenologists of wine astringency perception in
      the mouth.

PMID- 23173978
TI  - Transcranial brain sonography findings in two main variants of progressive
      supranuclear palsy.
AB  - BACKGROUND AND PURPOSE: Progressive supranuclear palsy (PSP) can occur with two
      main clinical presentations, classified as classical Richardson's syndrome (PSP
      RS) and as PSP-parkinsonism (PSP-P), the most common atypical PSP variant. The
      differential diagnosis between them is challenging. Therefore, we studied
      different ultrasound markers by transcranial sonography in individuals with PSP
      RS and PSP-P, to test their value in the diagnostic work up of these patients.
      METHODS: Transcranial sonography was performed in 21 patients with PSP-RS and 11
      patients with PSP-P. Echogenic sizes of the substantia nigra (SN) and the
      lenticular nuclei (LN), as well as the width of the third ventricle, were
      measured. RESULTS: Among the patients with PSP-RS and PSP-P, three (14%) and
      eight (73%) patients had a hyperechogenic SN (P = 0.020), respectively. Uni- or
      bilateral hyperechogenicity of the LN was observed in 67% and 36% of patients
      with PSP-RS and PSP-P, respectively (P = 0.101). Third ventricle was
      significantly wider in patients with PSP-RS (11.2 +/- 2.3 mm) when compared with
      patients with PSP-P (7.5 +/- 1.4 mm; P = 0.001). CONCLUSION: Our data, possibly
      reflecting pathological differences, primarily contribute supporting the view
      that the neurodegenerative process differs in the two PSP variants.

PMID- 23173979
TI  - Improvement in asthma quality of life in patients enrolled in a prospective study
      to increase lifestyle physical activity.
AB  - OBJECTIVE: Asthma patients know the benefits of exercise but often avoid physical
      activity because they are concerned that it will exacerbate asthma. The objective
      of this analysis was to assess longitudinal asthma status in 256 primary care
      patients in New York City enrolled in a trial to increase lifestyle physical
      activity. METHODS: Patients were randomized to two protocols to increase physical
      activity during a period of 12 months. At enrollment, patients completed the
      Asthma Quality of Life Questionnaire (AQLQ) and the Asthma Control Questionnaire
      (ACQ) and received asthma self-management instruction through an evaluative test
      and workbook. Exercise and self-management were reinforced every 2 months. The
      AQLQ was repeated every 4 months and the ACQ was repeated at 12 months. RESULTS:
      The mean age was 43 years and 75% were women. At 12 months there were clinically
      important increases in physical activity with no differences between groups;
      thus, data were pooled for asthma analyses. The enrollment AQLQ score was 5.0 +/-
      1.3 and increased to 5.9 +/- 1.1 corresponding to a clinically important
      difference. Correlations between AQLQ and physical activity were approximately
      0.35 (p < .0001) at each time point. In a mixed effects model, the variables
      associated with improvement in AQLQ scores over time were male sex, less severe
      asthma, not taking asthma maintenance medications, fewer depressive symptoms, and
      increased physical activity (all variables, p < .03). According to the ACQ,
      asthma was well controlled in 38% at enrollment and in 60% at 12 months (p <
      .0001). CONCLUSION: With attention to self-management, increased physical
      activity did not compromise asthma control and was associated with improved
      asthma.

PMID- 23173980
TI  - Molecular genetic analysis of 16 XP-C patients from Germany: environmental
      factors predominately contribute to phenotype variations.
AB  - Patients belonging to xeroderma pigmentosum (XP) complementation group C comprise
      one-third of all XP patients. Only four major reports compiled larger groups of
      XP-C patients from southern Europe (12 pts), North America (16 pts) and Africa
      (14 and 56 pts) as well as their genetic background (46 XPC mutations). We
      identified 16 XP-C patients from Germany. Interestingly, only five patients
      exhibited severe sun sensitivity. The mean age of XP diagnosis was 9.4 years, and
      the median age of the first skin cancer was 7 years. Neurological symptoms were
      absent in all but two patients. Primary fibroblasts from all 16 patients showed
      reduced post-UV cell survival (mean: 50% vs 93% in normal cells) and reduced
      reactivation of an UV-treated luciferase reporter gene (mean: 6.4% vs 30.7% in
      normal cells). XPC mRNA expression was also greatly reduced compared with normal
      cells (mean: 14.3%; range 8.3-25.7%) except in XP47MA (274.1%). All patients
      carried homozygous XPC mutations. Four mutations have been described previously:
      c.1747_1748delTG (found in 4/16), c.567 C>T (4/16), c.1839 C>T (1/16) and a
      complex insertion/deletion mutation in exon 9 (1/16). The novel frameshift
      mutations c.446_447delAG (2/16), c.1525insA (1/16) and c.2271delC (1/16) lead to
      truncated XPC proteins as does the novel nonsense mutation c.843C>T (1/16).
      XP47MA carries an interesting mutation (c.2538_2540delATC; p.Ile812del) resulting
      in an in-frame single amino acid deletion. This mutation results in a classical
      XP phenotype, a non-functional XPC protein, but elevated XPC mRNA expression. Our
      study indicates that extrinsic factors may contribute to XP-C symptom severity
      due to nonsense-mediated message decay.

PMID- 23173981
TI  - Spatial genetic and morphologic structure of wolves and coyotes in relation to
      environmental heterogeneity in a Canis hybrid zone.
AB  - Eastern wolves have hybridized extensively with coyotes and gray wolves and are
      listed as a 'species of special concern' in Canada. However, a distinct
      population of eastern wolves has been identified in Algonquin Provincial Park
      (APP) in Ontario. Previous studies of the diverse Canis hybrid zone adjacent to
      APP have not linked genetic analysis with field data to investigate genotype
      specific morphology or determine how resident animals of different ancestry are
      distributed across the landscape in relation to heterogeneous environmental
      conditions. Accordingly, we studied resident wolves and coyotes in and adjacent
      to APP to identify distinct Canis types, clarify the extent of the APP eastern
      wolf population beyond the park boundaries and investigate fine-scale spatial
      genetic structure and landscape-genotype associations in the hybrid zone. We
      documented three genetically distinct Canis types within the APP region that also
      differed morphologically, corresponding to putative gray wolves, eastern wolves
      and coyotes. We also documented a substantial number of hybrid individuals (36%)
      that were admixed between 2 or 3 of the Canis types. Breeding eastern wolves were
      less common outside of APP, but occurred in some unprotected areas where they
      were sympatric with a diverse combination of coyotes, gray wolves and hybrids. We
      found significant spatial genetic structure and identified a steep cline
      extending west from APP where the dominant genotype shifted abruptly from eastern
      wolves to coyotes and hybrids. The genotypic pattern to the south and northwest
      was a more complex mosaic of alternating genotypes. We modelled genetic ancestry
      in response to prey availability and human disturbance and found that individuals
      with greater wolf ancestry occupied areas of higher moose density and fewer
      roads. Our results clarify the structure of the Canis hybrid zone adjacent to APP
      and provide unique insight into environmental conditions influencing
      hybridization dynamics between wolves and coyotes.

PMID- 23173982
TI  - Environmental and demographic risk factors for campylobacteriosis: do various
      geographical scales tell the same story?
AB  - BACKGROUND: Campylobacter is a common cause of bacterial gastro-enteritis
      characterized by multiple environmental sources and transmission pathways.
      Ecological studies can be used to reveal important regional characteristics
      linked to campylobacteriosis risk, but their results can be influenced by the
      choice of geographical units of analysis. This study was undertaken to compare
      the associations between the incidence of campylobacteriosis in Quebec, Canada
      and various environmental characteristics using seven different sets of
      geographical units. METHODS: For each set of geographical unit, a conditional
      autoregressive model was used to model the incidence of reported cases of
      campylobacteriosis according to environmental (poultry density, ruminant density,
      slaughterhouse presence, temperature, and precipitation) and demographic
      (population density, level of education) characteristics. Models were compared in
      terms of number of significant predictors, differences in direction and magnitude
      of predictors, and fit of the models. RESULTS: In general, the number of
      significant predictors was reduced as the aggregation level increased. More
      aggregated scales tend to show larger but less precise estimates for all
      variables, with the exception of slaughterhouse presence. Regional
      characteristics associated with an increased regional risk of campylobacteriosis,
      for at least some geographical units, were high ruminant density, high poultry
      density, high population density, and presence of a large poultry slaughterhouse,
      whereas a reduction in risk was associated with a lower percentage of people with
      diplomas, a lower level of precipitation, and warmer temperature. Two clusters of
      elevated residual risk were observed, with different location and size depending
      on the geographical unit used. CONCLUSIONS: Overall, our results suggest that the
      use of municipality or census consolidated subdivision were the most optimal
      scales for studying environmental determinants of campylobacteriosis at a
      regional level. This study highlights the need for careful selection and analysis
      of geographical units when using ecological study designs.

PMID- 23173983
TI  - Microbiological food safety: a dilemma of developing societies.
AB  - Current food safety issues are deleteriously reshaping the life style of the
      population in the developing world. Socioeconomic status of the population in
      poorer economies is one of the major determinants to delineate the availability
      of safe food to the vulnerable population. Assessment of the prevalence of
      foodborne illness in developing world is the most neglected area to control
      disease. Botulism, Shigellosis, Campylobacteriosis, Escherichia coli infection,
      Staphylococcus aureus infection, Salmonellosis, Listeriosis and Cholerae are
      extensively prevalent and pose a major threat to human health in underdeveloped
      communities. The existing food safety status of many African, South Asian,
      Central, and South American developing countries is distressing therefore; it
      seems much timely to highlight the areas for the improvement to ensure the supply
      of safe food to the population in these regions. Extensive literature search at
      PubMed, Science Direct and Medline was carried out during the current year to
      catch on relevant data from 1976 to date, using selective terms like food safety,
      South East Asia, Africa, Central and South America, and foodborne illness etc.
      Efforts were made to restrict the search to low income countries of these regions
      with reference to specific foodborne pathogens. This report briefly discusses the
      present food safety situation in these developing countries and associated
      consequences as prime issues, suggesting foodborne illness to be the most
      distressing threat for human health and economic growth.

PMID- 23173985
TI  - Ankle/brachial index to everyone.
AB  - BACKGROUND: In the last years significant attention has been paid in identifying
      markers of subclinical atherosclerosis or of increased cardiovascular risk.
      METHOD: An abnormal ankle/brachial index (ABI) identifies patients affected by
      lower extremity peripheral arterial disease, and even more important, represents
      a powerful predictor of the development of future ischemic cardiovascular events.
      CONCLUSIONS: In our opinion, ABI is a cardiovascular risk prediction tool with
      very desirable properties that might become a routine measurement in clinical
      practice.

PMID- 23173986
TI  - The perspectives of bereaved family carers on dying at home: the study protocol
      of 'unpacking the home: family carers' reflections on dying at home.
AB  - BACKGROUND: Recent end of life care policy prioritises patient choice over place
      of care and in particular promotes dying at home. This policy is predicated on
      the assumption that there are family carers able and willing to provide care for
      the dying person. Through the accounts of bereaved family members, the 'Unpacking
      the home' study aims to gain an in-depth understanding of 'home' and the issues
      faced by family members caring for a dying older person at home; it also aims to
      examine the way the home is transformed in the process of providing end of life
      care, and offer a critical analysis of policies that aim to increase home deaths.
      This paper presents the protocol for this study. METHODS/DESIGN: A cross
      sectional qualitative study has been designed to achieve the study aims. In-depth
      interviews will be conducted in the north and south of England with 50 bereaved
      family carers to elicit their accounts of witnessing the dying in the home of an
      older person (50+ years). All interviews will be subjected to thematic analysis,
      and narrative analysis will be undertaken on a subset of 30 interview
      transcripts. A final phase of integration and policy analysis will be conducted
      towards the end of the study. User involvement is integral to this study, with
      service users actively engaged at every stage. DISCUSSION: This study will seek
      to take a qualitative approach by explicitly recognising that family carers are
      central to the experience of dying at home for older people, and they have needs
      that may be amenable to support and anticipatory planning. The strengths of this
      study, which include its interdisciplinary and participatory approach, and in
      depth data collection and analysis methods, will be explored. The limitations and
      challenges of this research will also be considered. This study seeks to make
      recommendations that will ensure that family carers receive appropriate and
      adequate support in caring for their loved ones at the end of life.

PMID- 23173984
TI  - Arsenic, asbestos and radon: emerging players in lung tumorigenesis.
AB  - The cause of lung cancer is generally attributed to tobacco smoking. However lung
      cancer in never smokers accounts for 10 to 25% of all lung cancer cases. Arsenic,
      asbestos and radon are three prominent non-tobacco carcinogens strongly
      associated with lung cancer. Exposure to these agents can lead to genetic and
      epigenetic alterations in tumor genomes, impacting genes and pathways involved in
      lung cancer development. Moreover, these agents not only exhibit unique
      mechanisms in causing genomic alterations, but also exert deleterious effects
      through common mechanisms, such as oxidative stress, commonly associated with
      carcinogenesis. This article provides a comprehensive review of arsenic,
      asbestos, and radon induced molecular mechanisms responsible for the generation
      of genetic and epigenetic alterations in lung cancer. A better understanding of
      the mode of action of these carcinogens will facilitate the prevention and
      management of lung cancer related to such environmental hazards.

PMID- 23173988
TI  - Striving for scientific stringency: a re-analysis of a randomised controlled
      trial considering first-time mothers' obstetric outcomes in relation to birth
      position.
AB  - BACKGROUND: The aim of this study was to compare maternal labour and birth
      outcomes between women who gave birth on a birth seat or in any other position
      for vaginal birth and further, to study the relationship between synthetic
      oxytocin augmentation and maternal blood loss, in a stratified sample. METHODS: A
      re-analysis of a randomized controlled trial in Sweden. An on-treatment analysis
      was used to study obstetrical outcomes for nulliparous women who gave birth on a
      birth seat (birth seat group) compared to birth in any other position for vaginal
      birth (control group). Data were collected between November 2006 and July 2009.
      The outcome measurements included perineal outcome, post partum blood loss,
      epidural analgesia, synthetic oxytocin augmentation and duration of labour.
      RESULTS: The major findings of this paper were that women giving birth on the
      birth seat had shorter duration of labour and were significantly less likely to
      receive synthetic oxytocin for augmentation in the second stage of labour.
      Significantly more women had an increased blood loss when giving birth on the
      birth seat, but had no difference in perineal outcomes. Blood loss was increased
      regardless of birth position if women had been exposed to synthetic oxytocin
      augmentation during the first stage of labour. CONCLUSIONS: The results of this
      analysis imply that women with a straightforward birth process may well benefit
      from giving birth on a birth seat without risk for any adverse obstetrical
      outcomes. However it is important to bear in mind that, women who received
      synthetic oxytocin during the first stage of labour may have an increased risk
      for greater blood loss when giving birth on a birth seat. Finally it is of vital
      importance to scrutinize the influence of synthetic oxytocin administered during
      the first stage of labour on blood loss postpartum, since excessive blood loss is
      a well-documented cause of maternal mortality worldwide and may cause severe
      maternal morbidity in high-income countries. TRIAL REGISTRATION: Unique Protocol
      ID: NCT01182038 ( http://register.clinicaltrials.gov).

PMID- 23173989
TI  - Assessing and addressing cardiovascular risk in adults with Turner syndrome.
AB  - Turner syndrome (TS), the result of a structurally abnormal or absent X
      chromosome, occurs in one in 2 000 live born females. The phenotype is highly
      variable, but short stature and gonadal dysgenesis are usually present. The main
      objective in adults with TS is health surveillance, but TS still causes a
      reduction in life expectancy of up to 13 years, with cardiovascular disease,
      congenital or acquired, as the major cause of an early death. While it has been
      established that all women with TS should undergo in-depth cardiovascular
      examination at diagnosis, advice on the cardiovascular management of women with
      TS is limited. Here, we provide a summary of our current practice within a
      multidisciplinary team, supported by our expertise in various aspects of
      cardiovascular risk management, and the evidence from research where it is
      available, with the aim of providing optimal support to our patients with TS.
      BACKGROUND: A dedicated Adult Turner Clinic was established in South East
      Scotland in 2002. This gynaecology-led clinic serves a population of roughly 1.2
      million and, currently, reviews around 50 women with TS annually. Referrals for
      adult care come from paediatrics or general practice. Following a series of
      individual case discussions regarding the management of more complex
      cardiovascular problems, we have assembled a dedicated multidisciplinary group to
      determine a timely cardiovascular screening strategy, a basis for specialist
      referral, and appropriate hypertension management. This team now includes a
      paediatric endocrinologist, gynaecologist, cardiologist (with an interest in
      inherited disorders), vascular radiologist and hypertension specialist. Here, we
      review the literature on cardiovascular disease in women with TS and, make
      recommendations, based on relatively limited high-quality evidence, together with
      our experience, on the optimal timing of cardiovascular screening.

PMID- 23173987
TI  - Recent advances in understanding viral evasion of type I interferon.
AB  - The type I interferon (IFN) system mediates a wide variety of antiviral effects
      and represents an important first barrier to virus infection. Consequently,
      viruses have developed an impressive diversity of tactics to circumvent IFN
      responses. Evasion strategies can involve preventing initial virus detection, via
      the disruption of the Toll-like receptors or the retinoic acid inducible gene I
      (RIG-I) -like receptors, or by avoiding the initial production of the ligands
      recognized by these receptors. An alternative approach is to preclude IFN
      production by disarming or degrading the transcription factors involved in the
      expression of IFN, such as interferon regulatory factor 3 (IRF3)/IRF7, nuclear
      factor-kappaB (NF-kappaB), or ATF-2/c-jun, or by inducing a general block on host
      cell transcription. Viruses also oppose IFN signalling, both by disturbing the
      type I IFN receptor and by impeding JAK/STAT signal transduction upon IFN
      receptor engagement. In addition, the global expression of IFN-stimulated genes
      (ISGs) can be obstructed via interference with epigenetic signalling, and
      specific ISGs can also be selectively targeted for inhibition. Finally, some
      viruses disrupt IFN responses by co-opting negative regulatory systems, whereas
      others use antiviral mechanisms to their own advantage. Here, we review recent
      developments in this field.

PMID- 23173990
TI  - Rectosigmoid stump washout as an alternative to permanent mucous fistula in
      patients undergoing subtotal colectomy for ulcerative colitis in emergency
      settings.
AB  - BACKGROUND: Restorative proctocolectomy with ileopouch-anal anastomosis (IPAA) is
      the treatment of choice for intractable or complicated ulcerative colitis(UC).
      Elderly patients often present with acute colitis requiring emergent subtotal
      colectomy(SC). Frail patients are at risk of developing septic complications
      related to the closed rectosigmoidal stump, often requiring formation of a second
      stoma to be reversed at the time of completion proctectomy. This carries nuisance
      to such exhausted patients. We propose a simple and inexpensive trick to avoid
      the need for creating a mucous fistula. METHODS: IPAA was performed as a 3-stage
      procedure in emergency settings. The rectosigmoidal stump was closed and placed
      subcutaneously; skin was closed over it. After SC, if patients showed signs of
      stump-related pelvic sepsis, a lavage of the rectal stump with povidone iodine
      solution and with saline was carried out as a rescue treatment aiming to avoid
      the need of opening the rectal stump to drain sepsis. RESULTS: Thirty-five
      patients underwent SC for UC between 1987 and 2012. The skin was closed over the
      closed stump in the 20. Seven patients out of these 20 experienced early stump
      related septic complication. In five cases, we were able to avoid opening of the
      rectal stump, and a second stoma was unnecessary. After opening the closed stump
      in the remaining ones, a prompt improving of symptoms was observed. CONCLUSIONS:
      Rectal washout was well tolerated and avoided a second stoma in five out of seven
      patients, with better quality of life and body perception after IPAA surgery.
      This is relevant when dealing with geriatric patients, needing to completely
      recover before undergoing completion proctectomy.

PMID- 23173991
TI  - An algorithm to derive the fraction of photosynthetically active radiation
      absorbed by photosynthetic elements of the canopy (FAPAR(ps)) from eddy
      covariance flux tower data.
AB  - The fraction of absorbed photosynthetically active radiation (FAPAR) is a key
      vegetation biophysical variable in most production efficiency models (PEMs).
      Operational FAPAR products derived from satellite data do not distinguish between
      the fraction of photosynthetically active radiation (PAR) absorbed by
      nonphotosynthetic and photosynthetic components of vegetation canopy, which would
      result in errors in representation of the exact absorbed PAR utilized in
      photosynthesis. The possibility of deriving only the fraction of PAR absorbed by
      photosynthetic elements of the canopy (i.e. FAPAR(ps) ) was investigated. The
      approach adopted involved inversion of net ecosystem exchange data from eddy
      covariance measurements to calculate FAPAR(ps) . The derived FAPAR(ps) was then
      related to three vegetation indices (i.e. Normalized Difference Vegetation Index
      (NDVI), Medium Resolution Imaging Spectrometer (MERIS) Terrestrial Chlorophyll
      Index (MTCI) and Enhanced Vegetation Index (EVI)) in an attempt to determine
      their potential as surrogates for FAPAR(ps) . Finally, the FAPAR(ps) was
      evaluated against two operational satellite data-derived FAPAR products (i.e.
      MODIS and CYCLOPES products). The maximum FAPAR(ps) from the inversion approach
      ranged between 0.6 and 0.8. The inversion approach also predicted site-specific
      Q10-modelled daytime respiration successfully (R2 > 0.8). The vegetation indices
      were positively correlated (R2 = 0.67-0.88) to the FAPAR(ps). Finally, the two
      operational FAPAR products overestimated the FAPAR(ps). This was attributed to
      the two products deriving FAPAR for the whole canopy rather than for only
      photosynthetic elements in the canopy.

PMID- 23173992
TI  - In situ-prepared composite materials of PEDOT: PSS buffer layer-metal
      nanoparticles and their application to organic solar cells.
AB  - We report an enhancement in the efficiency of organic solar cells via the
      incorporation of gold (Au) or silver (Ag) nanoparticles (NPs) in the hole
      transporting buffer layer of poly(3,4
      ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS), which was formed on
      an indium tin oxide (ITO) surface by the spin-coating of PEDOT:PSS-Au or Ag NPs
      composite solution. The composite solution was synthesized by a simple in situ
      preparation method which involved the reduction of chloroauric acid (HAuCl4) or
      silver nitrate (AgNO3) with sodium borohydride (NaBH4) solution in the presence
      of aqueous PEDOT:PSS media. The NPs were well dispersed in the PEDOT:PSS media
      and showed a characteristic absorption peak due to the surface plasmon resonance
      effect. Organic solar cells with the structure of ITO/PEDOT:PSS-Au, Ag NPs/poly(3
      hexylthiophene):[6,6]-phenyl-C61-butyric acid methyl ester (P3HT:PCBM)/LiF/Al
      exhibited an 8% improvement in their power conversion efficiency mainly due to
      the enlarged surface roughness of the PEDOT:PSS, which lead to an improvement in
      the charge collection and ultimately improvements in the short-circuit current
      density and fill factor.

PMID- 23173993
TI  - Young people's perspectives on the adoption of preventive measures for HIV/AIDS,
      malaria and family planning in South-West Uganda: focus group study.
AB  - BACKGROUND: Despite the possibility of preventing many cases of HIV, malaria and
      unplanned pregnancy, protective measures are often not taken by those at risk in
      Uganda. The study aim was to explore young people's perspectives on the reasons
      why this is so. METHODS: Focus groups were conducted with 100 secondary school
      and college students in Kanungu, Uganda in 2011. Three parallel groups considered
      HIV, malaria and family planning, and common messages were then explored jointly
      in a workshop based on the RE-AIM framework (Reach, Effectiveness, Adoption,
      Implementation and Maintenance). RESULTS: Participants identified various reasons
      why preventive action was not always taken. They worried about the effectiveness
      and side effects of several key interventions: condoms, antiretroviral treatment,
      various contraceptives and impregnated mosquito nets. Cost, rural isolation and
      the quality and availability of health services also limited the extent to which
      people were able to follow health advice. Although there was respect for policy
      supporting abstinence and fidelity, it was seen as hard to follow and offering
      inadequate protection when gender imbalance put pressure on women to have sex.
      CONCLUSIONS: There is an opportunity to improve the uptake of preventive measures
      by tackling the misconceptions and fears that participants reported with clear,
      evidence-based messages. This should be done in a way that encourages more open
      communication about reproductive health between men and women, that reaches out
      to isolated communities, that draws on both voluntary and government services and
      enlists young people so that they can shape their future.

PMID- 23173994
TI  - Increasing trend of HIV/AIDS among Arab and Jewish male persons in Israel, 1986
      2010.
AB  - OBJECTIVES: The aim of the study was to compare the HIV/AIDS burdens in Jewish
      and Arab Israeli males, as HIV/AIDS affects different population groups
      disproportionally. METHODS: The National HIV/AIDS Registry (NHAR) was used as the
      source of HIV/AIDS infection records, while the Israeli Central Bureau of
      Statistics was used to determine group-specific disease rates. RESULTS: Between
      1986 and 2010, 3499 HIV/AIDS-infected male Israelis were reported to the NHAR:
      3369 (96.3%) Jews and 130 (3.7%) Arabs, with an average annual incidence of 5.5
      and 0.8 per 100 000 of the population, respectively (P = 0.05). Of the Jews, 1018
      (29.9%) were born in Ethiopia, while 2389 were Jews who were not Ethiopian-born
      (JNE). Most of the Arabs (n = 99; 74.8%) were Muslims, followed by Christians
      (21; 16.2%) and Druze (13; 10%). AIDS rather than HIV infection at the time of
      reporting was diagnosed in 568 (23.8%) of the JNE and 31 (23.8%) of the Arabs (p
      = 1). The most affected age group was those aged 25-34 years among the JNE and
      those aged 20-24 years among the Arabs, and the respective cumulative death rates
      were 24.9% (n = 594) and 32.5% (n = 40) (P = 0.1). The point prevalences in 2010
      were 58.4 and 11.4 per 100 000 for JNE and Arabs, and in adults aged 15-59 years
      they were 71.5 and 26.3 per 100 000, respectively. In Muslims, Christians and
      Druze, the point prevalences were 4.2, 11.2 and 7.1 per 100 000, and in adults
      aged 15-59 years they were 22.6, 42.9 and 29.4, respectively. The most common
      risk group among JNE was men who have sex with men (MSM; n = 1223; 51.2%),
      followed by injecting drug users (n = 661; 27.7%), while among Arabs it was MSM
      (n = 63; 48.1%), followed by heterosexuals (n = 36; 27.3%). CONCLUSIONS: The
      HIV/AIDS burden in Israeli Arab males was significantly lower than that in Jews,
      and in both populations the most common risk group was MSM, with the proportion
      of MSM increasing with time.

PMID- 23173995
TI  - Patients' experience with cancer care: a qualitative study in family practice.
AB  - BACKGROUND: Continuity is an important aspect of cancer care that is often a
      challenge owing to the movement of patients between family practice, cancer
      clinics, and hospitals. OBJECTIVES: To investigate the experiences of cancer
      patients in relation to continuity of care. METHODS: A qualitative study was
      conducted in a family practice setting. Semi-structured interviews were used for
      data collection. 10 cancer patients with a wide variation in their disease
      duration and experiences with medical care were interviewed. Open questions were
      used to encourage patients to express their personal experiences with cancer
      care. The interviews were recorded, transcribed and analysed by three researchers
      using thematic analysis. RESULTS: Cancer patients experienced a lack of
      information concerning cancer and its treatment. They also perceived that the
      cancer treatment made them suffer. In the patients' opinion, the family doctor
      has a limited role in cancer care. However, the patients felt that the family
      doctor should be aware of their health. The patients' satisfaction with the
      oncologist's care was high. They considered that their role in cancer care was to
      mediate an exchange of information between the oncologist and the family doctor.
      CONCLUSION: Cancer patients experience continuity of care in several ways:
      continuity in cancer care should be implemented by co-ordinating activities, such
      as regular check-ups, a clear timeframe and provision of adequate information. In
      addition, communication between the primary and secondary sector could be
      improved.

PMID- 23173996
TI  - Acute cough: the use of antibiotics and health care services in an urban health
      centre in Israel.
AB  - BACKGROUND: Acute cough, often caused by a viral respiratory infection, is a
      common symptom in primary care. Although clinical guidelines recommend
      symptomatic treatment for acute cough, antibiotics are frequently prescribed.
      OBJECTIVE: To determine antibiotic prescribing for acute cough at the initial
      consultation and to follow subsequent medical consultations and use of
      medications. METHODS: The study population included all adult patients with acute
      cough who visited general practitioners from one health centre (HC) during four
      months. Information was gathered from medical charts and telephone interviews
      conducted two weeks later. RESULTS: Fifty six of three hundred and thirty eight
      participants (16.6%) received antibiotics at the initial visit. Eighty three
      participants made subsequent visits to the HC, 40 participants visited physicians
      outside the HC and nine participants visited both. During two weeks after the
      initial visit, 35 participants were prescribed antibiotics (eight in the HC, 27
      outside the HC). Total antibiotic use rose to 27% (91/338) during the study
      period. At that time 98 (29%) of the participants reported they were still ill.
      Multivariate analysis showed that expectation to receive antibiotics was reported
      at a higher rate by the participants who received it, as compared to those who
      did not (32.2% versus 13.2%, OR: 2.3; 95% CI: 1.2-4.8). Receiving antibiotics was
      also associated with use of health services (20.3% versus 9.9%, OR: 2.7; 95% CI:
      1.2-6.2). CONCLUSIONS: Patient activism during the course of acute cough is
      associated with increased antibiotic use.

PMID- 23173997
TI  - Observational approaches in the study of the effects of Total Suspended
      Particulates (TSP) exposure.
AB  - Literature contains mainly reports of observations based on time-series, or those
      of a case-crossover analysis design or, although less frequently, case control
      studies. However, data obtained by different approaches are difficult to compare
      based on different and non-homogenous population. The principal aim of this
      research was to compare the estimated risks obtained by differing approaches
      based on the same population study in the period 2006-2009. The data were based
      on a total of 44,200 residents in the city of Turin, hospitalised for respiratory
      diseases (ICD 460-519) in the period 2006-2009. Total suspended particulates
      (TSP), measured in ug/m(3), are the most commonly used predictors of urban
      pollution. The association between hospital admission for respiratory diseases
      and TSP exposure was investigated using at the same time the time-series, case
      crossover and case-control approaches. The analyses show a general comparability
      of the case-crossover design stratified for time and the time-series approach,
      and the case control approach provided a more unstable estimation of risks. In
      conclusion, our results seem to indicate that the different approaches studied
      seem to offer comparable results.

PMID- 23173998
TI  - Young GPs and transforming primary care.

PMID- 23173999
TI  - L-carnitine supplementation in dialysis: treatment in quest of disease.
AB  - L-Carnitine (LC) administration has been recommended for specific indications in
      dialysis patients, including epoetin-resistant anemia, intradialytic hypotension,
      cardiomyopathy, fatigue, muscle weakness, and exercise performance; it may
      ameliorate insulin resistance, inflammation, and protein wasting. Use of LC for
      anemia and intradialytic hypotension has been approved for reimbursement by the
      Centers for Medicare and Medicaid Services. Yet, the data to support these
      recommendations are inadequate and have not been bolstered over several decades.
      LC administration continues to appeal to nephrologists because its use in
      dialysis patients has an attractive rationale, it addresses problems that persist
      despite dialysis, it is safe, and the existing literature does not refute its
      use. Nevertheless, definitive trials to justify LC administration have not been
      conducted and are increasingly unlikely to be funded. In an era of shrinking
      resources and bundling of dialysis services, the use of LC in dialysis patients
      will, appropriately, diminish.

PMID- 23174000
TI  - Challenges in identifying barriers to adoption in a theory-based implementation
      study: lessons for future implementation studies.
AB  - BACKGROUND: Exploring barriers to the uptake of research based recommendations
      into practice is an important part of the development of implementation
      programmes. Techniques to identify barriers can include use of theory-informed
      questionnaires and qualitative interviews. Conceptualising and measuring theory
      informed factors, and engaging health professionals' to uncover all potential
      barriers, can be a difficult task. This paper presents a case study of the
      process of trying to identify, systematically, the key factors influencing health
      professionals' referrals for women diagnosed with mild to moderate postnatal
      depression for psychological treatment. The paper illustrates how the factors
      were conceptualised and measured and explores the real world challenges
      experienced, with implications for future implementation studies. METHODS: Theory
      informed factors were conceptualised and measured using a questionnaire and
      interviews. The questionnaire was piloted, before being administered to general
      practitioners, practice nurses and health visitors working in general practices
      in one area of the UK NHS. The interviews were conducted with a small sample of
      general practitioners who had not completed the questionnaire, further exploring
      factors influencing their referral decisions in the local context. RESULTS: The
      response rate to the questionnaire was low (19%), despite selecting the
      recommendation to target through engagement with local stakeholders and surveying
      local health professionals, and despite using two reminders, an incentive prize,
      and phone calls to practice managers to bolster response rates. CONCLUSIONS: Two
      significant challenges to achieving higher response rates and successfully
      exploring local context were identified: the difficulties of developing a robust-
      but feasible- questionnaire to explore theory-informed factors, and targeting
      recommendations that are important to policy makers, but which health
      professionals view as unimportant. This case study highlights the "trade-off"
      between scientifically rigorous collection of data against the pragmatism and
      flexibility requirements of "real world" implementation. Future implementation
      studies should explore different ways of identifying factors influencing the
      adoption of recommendations to bridge this gulf.

PMID- 23174001
TI  - Access to wound dressings for patients living with epidermolysis bullosa - an
      Australian perspective.
AB  - Epidermolysis Bullosa (EB) is a rare genetic skin disorder characterised by
      fragility and blistering of skin and mucous membranes. Skin can blister and shear
      away from minimal friction, trauma and every day activities. The disease causes a
      wide range of complications but wound care is the major challenge to severe EB,
      and good wound care is an essential part of wound management. The goal of wound
      care was to choose a product that protects the fragile skin, limits friction,
      decreases pain and promotes healing. However, access to wound dressings for those
      people living with EB is challenging. This article discusses the availability of
      EB dressings in a number of countries around the world and also describes an
      innovative National Epidermolysis Bullosa Dressings Scheme (NEBDS) in Australia,
      which aims to improve the quality of life of people with EB, by reducing the
      financial burden associated with the provision of dressings accordingly. 

PMID- 23174002
TI  - Design, synthesis and biological evaluation of novel betulinic acid derivatives.
AB  - BACKGROUND: Tumor, is one of the major reason for human death, due to its
      widespread occurrence. Betulinic acid derivatives have attracted considerable
      attention as cancer chemopreventive agents and also as cancer therapeutics. Many
      of its derivatives inhibit the growth of human cancer cell lines by triggering
      apoptosis. With this background, we planned to synthesize a series of betulinic
      acid derivatives to assess their antiproliferation efficacy on human cancer cell
      lines. RESULTS: A series of novel betulinic acid derivatives were designed and
      synthesized as highlighted by the preliminary antitumor evaluation against MGC
      803, PC3, A375, Bcap-37 and A431 human cancer cell lines in vitro. The
      pharmacological results showed that some of the compounds displayed moderate to
      high levels of antitumor activities with most of new exhibiting higher inhibitory
      activities compared to BA. The IC50 values of compound 3c on the five cancer cell
      lines were 2.3, 4.6, 3.3, 3.6, and 4.3 MUM, respectively. Subsequent fluorescence
      staining and flow cytometry analysis (FCM) indicated that compound 3c could
      induce apoptosis in MGC-803 and PC3 cell lines, and the apoptosis ratios reached
      the peak (37.38% and 33.74%) after 36 h of treatment at 10 MUM. CONCLUSIONS: This
      study suggests that most of betulinic acid derivatives could inhibit the growth
      of human cancer cell lines. Furthermore, compound 3c could induce apoptosis of
      cancer cells.

PMID- 23174003
TI  - Salinity-tolerant larvae of mosquito vectors in the tropical coast of Jaffna, Sri
      Lanka and the effect of salinity on the toxicity of Bacillus thuringiensis to
      Aedes aegypti larvae.
AB  - BACKGROUND: Dengue, chikungunya, malaria, filariasis and Japanese encephalitis
      are common mosquito-borne diseases endemic to Sri Lanka. Aedes aegypti and Aedes
      albopictus, the major vectors of dengue, were recently shown to undergo pre
      imaginal development in brackish water bodies in the island. A limited survey of
      selected coastal localities of the Jaffna district in northern Sri Lanka was
      carried out to identify mosquito species undergoing pre-imaginal development in
      brackish and saline waters. The effect of salinity on the toxicity of Bacillus
      thuringiensis israelensis larvicide to Ae. aegypti larvae at salinity levels
      naturally tolerated by Ae. aegypti was examined. METHODS: Larvae collected at the
      selected sites along the Jaffna coast were identified and salinity of habitat
      water determined in the laboratory. The LC50 and LC90 of B. thuringiensis toxin,
      the active ingredient of a commercial formulation of the larvicide BACTIVEC(r),
      were determined with Ae. aegypti larvae. Bioassays were also carried out at
      salinities varying from 0 to 18 ppt to determine the toxicity of Bacillus
      thuringiensis to fresh and brackish water-derived larvae of Ae. aegypti. RESULTS:
      Larvae of four Anopheles, two Aedes, one Culex and one Lutzia species were
      collected from brackish and saline sites with salinity in the range 2 to 68 ppt.
      The LC50 and LC90 of B. thuringiensis toxin for the second instar larvae of Ae.
      aegypti in fresh water were 0.006 ppm and 0.013 ppm respectively, with
      corresponding values for brackish water populations of 0.008 and 0.012 ppm
      respectively. One hundred percent survival of second instar fresh water and
      brackish water-derived Ae. aegypti larvae was recorded at salinity up to 10 and
      12 ppt and 100% mortality at 16 and 18 ppt, yielding an LC90 for salinity of 13.9
      ppt and 15.4 ppt at 24 h post-treatment respectively for the two populations.
      Statistical analysis showed significantly reduced toxicity of B. thuringiensis to
      fresh and brackish water-derived Ae. aegypti larvae at high salinities.
      CONCLUSION: A variety of mosquito vectors of human diseases undergo pre-imaginal
      development in brackish or saline waters in coastal areas of the Jaffna district
      in northern Sri Lanka. Salinity has a small but significant negative impact on
      the toxicity of B. thuringiensis toxin to Ae. aegypti larvae at salinity levels
      where Ae. aegypti larvae are found in the environment. This has implications for
      the use of B. thuringiensis toxin as a larvicide in brackish waters.

PMID- 23174004
TI  - Adsorption of the linear poly(ethyleneimine) precursor poly(2-ethyl-2-oxazoline)
      and sodium dodecyl sulfate mixtures at the air-water interface: the impact of
      modification of the poly(ethyleneimine) functionality.
AB  - The adsorption of the polymer-surfactant mixture of poly(2-ethyl-2-oxazoline)
      sodium dodecyl sulfate at the air-water interface has been studied by neutron
      reflectivity and surface tension. The observed patterns of adsorption more
      closely resemble those encountered in weakly interacting polymer-surfactant
      mixtures, rather than the pronounced enhancements in adsorption observed in
      strongly interacting polymer-surfactant mixtures, such as in the related
      poly(ethyleneimine)-sodium dodecyl sulfate mixtures. The adsorption was found to
      be strongly dependent on solution pH, polymer molecular weight, and polymer
      concentration. At the lower and higher molecular weights studied, there was
      little enhancement in the sodium dodecyl sulfate adsorption at low sodium dodecyl
      sulfate concentrations, whereas at the intermediate polymer molecular weights,
      some enhancement in the adsorption was observed. For the higher-molecular-weight
      polymers and at increasingly higher polymer concentrations, a significant
      reduction of the surfactant at the interface compared to pure sodium dodecyl
      sulfate occurred for sodium dodecyl sulfate concentrations between the critical
      aggregation concentration and the critical micellar concentration. The results
      illustrate the important role of modifying the functionality of
      poly(ethyleneimine) on surface adsorption.

PMID- 23174005
TI  - Population genomics based on low coverage sequencing: how low should we go?
AB  - Research in molecular ecology is now often based on large numbers of DNA sequence
      reads. Given a time and financial budget for DNA sequencing, the question arises
      as to how to allocate the finite number of sequence reads among three dimensions:
      (i) sequencing individual nucleotide positions repeatedly and achieving high
      confidence in the true genotype of individuals, (ii) sampling larger numbers of
      individuals from a population, and (iii) sampling a larger fraction of the
      genome. Leaving aside the question of what fraction of the genome to sample, we
      analyze the trade-off between repeatedly sequencing the same nucleotide position
      (coverage depth) and the number of individuals in the sample. We review simple
      Bayesian models for allele frequencies and utilize these in the analysis of how
      to obtain maximal information about population genetic parameters. The models
      indicate that sampling larger numbers of individuals, at the expense of coverage
      depth per nucleotide position, provides more information about population
      parameters. Dividing the sequencing effort maximally among individuals and
      obtaining approximately one read per locus and individual (1 * coverage) yields
      the most information about a population. Some analyses require genetic parameters
      for individuals, in which case Bayesian population models also support inference
      from lower coverage sequence data than are required for simple likelihood models.
      Low coverage sequencing is not only sufficient to support inference, but it is
      optimal to design studies to utilize low coverage because they will yield highly
      accurate and precise parameter estimates based on more individuals or sites in
      the genome.

PMID- 23174006
TI  - A curvilinear nomogram of peak expiratory flow rate for the young.
AB  - OBJECTIVE: Peak expiratory flow rates (PEFRs) differ among populations and
      between times. The new EU scale of the mini-Wright flow-meter has been introduced
      since 2004. This study updated the PEFR nomograms with the new scale for Chinese
      children and adolescents (aged 6-19 years) in Hong Kong. METHODS: A convenience
      sample was recruited from 34 primary care practices (patients'
      companions/children) and four schools. Standardization workshops were run for the
      physicians, and the proper use of the flow-meter was demonstrated to students
      prior to the data collection. Brand new meters were used. For each sex, the
      linear regression model was used to determine the relationship between PEFR and
      the variables of age and body height. The open-source software PyNomo was used to
      generate the nomograms. RESULTS: After excluding 66 participants with
      past/current history of respiratory tract diseases, heart disease, incomplete
      data, and poor effort, PEFRs were collected from 798 males and 794 females. The
      PEFR had a linear relationship with age but a curvilinear relationship with
      height. The regression equations for predicted PEFR were ln(PEFR) =
      1.810256*ln(height) + 0.038297*age - 3.734139 for males and ln(PEFR) =
      1.525509*ln(height) + 0.033275*age - 2.368592 for females. The corresponding
      nomograms were constructed. They were tested with 230 patients in primary care;
      9.6% (12 males and 10 females) had PEFR less than the predicted value by >=20%.
      CONCLUSION: The body height was a stronger determinant than age for PEFR. The
      predicted PEFR with these determinants bear a curvilinear relationship.

PMID- 23174007
TI  - Factors associated with the occurrence and level of Isospora suis oocyst
      excretion in nursing piglets of Greek farrow-to-finish herds.
AB  - BACKGROUND: Piglet isosporosis is one of the most common parasitic diseases in
      modern pig production. To prevent clinical disease, prophylactic treatment of
      piglets with toltrazuril (BAYCOX(r) 5%, Bayer HealthCare, Animal Health, Monheim,
      Germany) is widely practiced in the past 20 years. There are only very few
      reports documenting the likely effect of managerial practices, such as hygiene
      measures, all-in-all-out management of farrowing facilities and piglet
      manipulations, and/or farm-specific environment - i.e. design and materials of
      the farrowing pen and room - in the risk of disease occurrence and transmission.
      Therefore, in this cross-sectional study, we identified litter- and herd-level
      factors associated with the odds and the level of Isospora suis oocyst excretion
      in nursing piglets of Greek farrow-to-finish pig herds. Faecal samples were
      collected from 314 liters of 55 randomly selected herds. Oocyst counts were
      determined by a modified McMaster technique and possible risk-factor data were
      collected through a questionnaire. In the analysis, we employed a two-part model
      that simultaneously assessed the odds and the level of oocyst excretion. RESULTS:
      Factors associated with lower odds of oocyst excretion were: use of toltrazuril
      treatment, all-in all-out management of the farrowing rooms, no cross-fostering
      or fostering during the first 24 hours after farrowing, plastic flooring in the
      farrowing pens, farrowing rooms with more than fourteen farrowing pens and
      employment of more than two caretakers in the farrowing section. Factors
      associated with lower oocyst excretion level were: use of toltrazuril treatment
      and caretakers averting from entering into farrowing pens. CONCLUSION: Apart from
      prophylactic treatment with toltrazuril, the risk and the level of I. suis oocyst
      excretion from piglets in their second week of life, was associated with
      managerial and environmental factors. Changes in these factors, which may enhance
      prevention of piglet isosporosis - either alternatively or supplementary to
      medical control - are of increasing importance because of the likely development
      of resistant parasites under the currently widespread use of anticoccidial
      compounds.

PMID- 23174008
TI  - Endovascular treatment of lower extremity arteries is associated with an improved
      outcome in diabetic patients affected by intermittent claudication.
AB  - BACKGROUND: Lower extremity peripheral arterial disease (LE-PAD) is a highly
      prevalent condition among diabetic patients, associated with reduced walking
      capacity and a high incidence of cardiovascular events. Endovascular
      revascularization of lower extremities arteries improves walking performance and
      quality of life of diabetic patients affected by intermittent claudication, but
      few studies evaluated the impact of revascularization on cardiovascular outcome
      in this high-risk population. Accordingly, in the present study we evaluated if
      leg-ischemia resolution by effective lower limbs percutaneous revascularization
      can also impact cardiovascular outcome in a homogeneous group of diabetic
      patients affected by intermittent claudication. METHODS: 236 diabetic patients
      affected by LE-PAD at stage II of Fontaine's classification, with ankle/brachial
      index <= 0.90 and one or more hemodynamically significant stenosis in at least
      one artery of the ileo-femoro-popliteal axis were enrolled in the study.
      According to the Trans-Atlantic Inter Society Consensus II recommendations, 123
      (52.1%) underwent percutaneous transluminal angioplasty (PTA group), while 113
      (47.9%) underwent conservative medical therapy only (MT group). The incidence of
      major cardiovascular events (cardiovascular death, myocardial infarction,
      ischemic stroke, coronary or carotid revascularization) was prospectively
      analyzed with Kaplan-Meier curves and the risk of developing a cardiovascular
      event calculated by Cox analyses. RESULTS: No baseline difference in
      cardiovascular risk factors were observed between the PTA and MT groups, except
      for a lower prevalence of males in PTA group (74.8% vs. 85.8%, p=0.034).
      Furthermore, patients in the PTA group showed a worse walking capacity as
      expressed by maximum walking distance (108.7 +/- 300.9 vs 378.4 +/- 552.3 meters,
      p<0.001). During a median follow-up of 20 months (12.0-29.0), the incidence of
      cardiovascular events was markedly lower in patients in the PTA group with
      respect to patients in the MT group (7.3% vs. 22.1%, p=0.001), and patients of
      the MT group had at Cox analysis a 3.9 increased risk with respect to PTA group,
      after adjustment for potential confounding factors (95% CI 1.1-15.3, p=0.049).
      CONCLUSIONS: The present study shows that lower limbs revascularization of
      diabetic patients affected by intermittent claudication, in addition to improve
      walking performance, is associated with a reduction in the incidence of future
      major cardiovascular events.

PMID- 23174009
TI  - Early sexual behaviour and Chlamydia trachomatis infection - a population based
      cross-sectional study on gender differences among adolescents in Norway.
AB  - BACKGROUND: Early sexual behaviour has been shown to differ significantly between
      genders, but few studies have addressed this topic to explain the commonly
      observed differences in chlamydia rates between adolescent girls and boys. Our
      study aimed to determine chlamydia prevalence in adolescents aged 15-20 years in
      a high-incidence area in Norway, and to identify gender-specific early sexual
      behaviours associated with infection. METHODS: A population based cross-sectional
      study was conducted among all high school students in five towns in Finnmark
      county in 2009, using a web-based questionnaire and real-time Chlamydia
      trachomatis PCR in first-void urine samples (participation rate 85%, 800
      girls/818 boys, mean age 17.2 years). Crude and multivariable logistic regression
      models were applied with chlamydia test result as dependent variable. RESULTS:
      Prevalence of chlamydia infection was 5.7% (95% confidence interval, CI, 4.4
      7.3%). Girls were twice as likely to be infected as boys (7.3%, 5.3-9.7 vs 3.9%,
      2.3-6.0). Girls reported earlier sexual debut, older partners, higher lifetime
      number of partners, and were poorer condom users. In girls, higher maternal
      education (odds ratio, OR, 2.2, 95% CI 1.1-4.4), >=2 sexual partners past 6
      months (OR 3.6, 1.8-7.3), and partner meeting venue at a private party, bar or
      disco (OR 5.0, 1.1-22.7) increased the odds of infection in the multivariable
      model. In boys, condom use at first intercourse (OR 0.06, 0.01-0.42) decreased
      the odds of infection, while having an older last sexual partner (OR 3.7, 1.3
      11.0) increased the odds. In all participants, the risk of infection increased if
      residence outside the family home during school year (OR 2.0, 1.2-3.6), and
      decreased if condom was used at last intercourse (OR 0.2, 0.1-0.8). CONCLUSIONS:
      We detected significant gender differences in chlamydia prevalence and sexual
      behaviours, and accordingly differing independent risk factors for chlamydia
      infection. We suggest that accumulation of essentially different experiences in
      the early sexually active years contribute to gender disparities in chlamydia
      risk in individuals this age. Gender-specific approaches may be the best
      alternative to control chlamydia infection in age group 15-20 years.

PMID- 23174010
TI  - Factor VIII Bypassing Activity (FEIBA) assays: standardization and development of
      the 1st NIBSC Working Standard for FEIBA--results from a collaborative study.
AB  - Factor-Eight-Inhibitor-Bypassing-Activity (FEIBA) is a bypassing-agent used to
      control spontaneous bleeding or cover surgical interventions in Haemophiliacs who
      develop neutralizing antibodies against FVIII/FIX. The market lot-release of
      FEIBA is dependent on specific clot-based assays, carried out by both the
      manufacturer and regulatory authorities, relative to manufacturer's in-house
      standards, which are produced on a small-scale and are replaced frequently. We
      sought to standardize the FEIBA assay by developing a FEIBA primary standard
      which would be internationally available in sufficiently large quantities, with a
      predicted lifetime of many years. A collaborative study involving the
      manufacturer and three regulatory authorities, was carried out in which a
      candidate material, sample B (06/172), was calibrated by assays relative to the
      manufacturer's in-house FEIBA standards (C and D). All laboratories used their
      routine validated methods (16 APTT-assays, 8 ACTIN-FS-assays and 27 DAPTTIN
      assays). Intra-laboratory geometric coefficients of variation (GCVs) for
      candidate B ranged from 3% to 29% (GCVs <9% from majority of labs). Assessment of
      inter-laboratory variability gave overall GCV values of 6.9% and 4.4% relative to
      standards C and D, respectively, for all methods. There was good agreement in
      potency estimation between laboratories using each of the three methods, with the
      overall potencies by the three methods differing by less than 10% of the overall
      mean, giving an overall combined potency of 28.0 units per ampoule. All
      participants agreed that candidate B (06/172) be established as the 1st NIBSC
      Working Standard for FEIBA with an assigned potency of 28.0 units per ampoule,
      based on combined results for both methods, relative to either standard C or D.

PMID- 23174011
TI  - The roles of female and hermaphroditic flowers in the gynodioecious
      gynomonoecious Silene littorea: insights into the phenology of sex expression.
AB  - Some gynodioecious species have intermediate individuals that bear both female
      and hermaphroditic flowers. This phenomenon is known as a gynodioecious
      gynomonoecious sexual system. Gender expression in such species has received
      little attention in the past, and the phenologies of male and female functions
      have also yet to be explored. In this study, we examined variations in gender
      patterns, their effects on female reproductive success and sex expression in
      depth throughout the flowering period in two populations. The studied populations
      of Silene littorea contained mostly gynomonoecious plants and the number of pure
      females was very low. The gynomonoecious plants showed high variability in the
      total proportion of female flowers. In addition, the proportion of female flowers
      in each plant varied widely across the flowering season. Although there was a
      trend towards maleness, our measures of functional gender suggested that most
      plants transmit their genes via both pollen and ovules. Fruit set and seed set
      were not significantly different among populations; in contrast, flower
      production significantly varied between the two populations - and among plants -
      with consequent variation in total seed production. Conversely, gender and sex
      expression were similar in both populations. Plants with higher phenotypic
      femaleness did not have higher fruit set, seed set or total female fecundity. The
      mating environment fluctuated little across the flowering period, but
      fluctuations were higher in the population with low flower production. We
      therefore conclude that the high proportion of gynomonoecious individuals in our
      studied populations of S. littorea may be advantageous for the species, providing
      the benefits of both hermaphroditic and female flowers. 

PMID- 23174012
TI  - Hospital-wide breastfeeding rates vs. breastmilk provision for very-low-birth
      weight infants.
AB  - AIM: To investigate the relationship between breastmilk feeding in very-low-birth
      weight infants in the neonatal intensive care unit and breastmilk feeding rates
      for all newborns by hospital. METHODS: This was a cross-sectional study of 111
      California hospitals in 2007 and 2008. Correlation coefficients were calculated
      between overall hospital breastfeeding rates and breastmilk feeding rates of very
      low-birth-weight infants. Hospitals were categorized in quartiles by crude and
      adjusted very-low-birth-weight infant rates to compare rankings between measures.
      RESULTS: Correlation between breastmilk feeding rates of very-low-birth-weight
      infants and overall breastfeeding rates varied by neonatal intensive care unit
      level of care from 0.13 for intermediate hospitals to 0.48 for regional
      hospitals. For hospitals categorized in the top quartile according to overall
      breastfeeding rate, only 46% were in the top quartile for both crude and adjusted
      very-low-birth-weight infant rates. On the other hand, when considering the
      lowest quartile for overall breastfeeding hospitals, three of 27 (11%) actually
      were performing in the top quartile of performance for very-low-birth-weight
      infant rates. CONCLUSIONS: Reporting hospital overall breastfeeding rates and
      neonatal intensive care unit breastmilk provision rates separately may give an
      incomplete picture of quality of care.

PMID- 23174013
TI  - Plasma specific miRNAs as predictive biomarkers for diagnosis and prognosis of
      glioma.
AB  - OBJECTIVE: Glioblastoma multiforme (GBM) is a highly malignant brain tumor with a
      poor prognosis. MicroRNAs (miRNAs) are a class of small non-coding RNAs,
      approximately 21-25 nucleotides in length. Recently, some researchers have
      demonstrated that plasma miRNAs are sensitive and specific biomarkers of various
      cancers. The primary aim of the study is to investigate whether miRNAs present in
      the plasma of GBM patients can be used as diagnostic biomarkers and are
      associated with glioma classification and clinical treatment. MATERIALS AND
      METHODS: Plasma samples were attained by venipuncture from 50 patients and 10
      healthy donors. Plasma levels of miRNAs were determined by real-time quantitative
      polymerase chain reaction. RESULTS: The plasma levels of miR-21, miR-128 and miR
      342-3p were significantly altered in GBM patients compared to normal controls and
      could discriminate glioma from healthy controls with high specificity and
      sensitivity. However, these three miRNAs were not significantly changed in
      patients with other brain tumors such as meningioma or pituitary adenoma.
      Furthermore, the plasma levels of these three miRNAs in GBM patients treated by
      operation and chemo-radiation almost revived to normal levels. Finally, we also
      demonstrated that miR-128 and miR-342-3p were positively correlated with
      histopathological grades of glioma. CONCLUSIONS: These findings suggest that
      plasma specific miRNAs have potential use as novel biomarkers of glioma and may
      be useful in clinical management for glioma patients.

PMID- 23174014
TI  - Salivary biomarkers of oral health: a cross-sectional study.
AB  - AIM: Saliva is a useful diagnostic fluid for oral-related diseases. Monitoring
      salivary biomarkers for oral and systemic diseases could become an important
      complement to clinical examinations in epidemiological surveys. Recent findings
      indicate that it is possible to detect biomarkers for oral diseases within saliva
      samples. The aim of this study was to investigate if known salivary biomarkers
      could be used for epidemiological studies for detection of periodontitis.
      MATERIALS AND METHODS: A randomly selected sample of adults (20-89 years) living
      in Southern Sweden were invited to participate. Four hundred and fifty-one
      individuals were examined clinically using standard examination procedures.
      Stimulated saliva samples were collected and analysed for concentrations of IL
      1beta, -6, -8, lysozyme, matrix metalloproteinases (MMP)-8 and tissue inhibitor
      of metalloproteinase (TIMP)-1 using ELISA, immunofluorometric assay or Luminex
      assays. RESULTS: Patients with severe periodontitis presented with elevated
      salivary concentrations of IL-1beta (p < 0.001) and MMP-8 (p < 0.001). In
      addition, the MMP-8/TIMP-1 ratio was significantly higher in the severe
      periodontitis group (p < 0.001). Smokers compared with non-smokers showed
      slightly lower concentrations of IL-8 (p < 0.05) and MMP-8 (p = 0.052).
      CONCLUSION: This investigation shows that IL-1beta, MMP-8 and the ratio of MMP
      8/TIMP-1 could be used as markers of periodontal disease in larger patient
      populations.

PMID- 23174015
TI  - Bioinformatics Resource Manager v2.3: an integrated software environment for
      systems biology with microRNA and cross-species analysis tools.
AB  - BACKGROUND: MicroRNAs (miRNAs) are noncoding RNAs that direct post
      transcriptional regulation of protein coding genes. Recent studies have shown
      miRNAs are important for controlling many biological processes, including nervous
      system development, and are highly conserved across species. Given their
      importance, computational tools are necessary for analysis, interpretation and
      integration of high-throughput (HTP) miRNA data in an increasing number of model
      species. The Bioinformatics Resource Manager (BRM) v2.3 is a software environment
      for data management, mining, integration and functional annotation of HTP
      biological data. In this study, we report recent updates to BRM for miRNA data
      analysis and cross-species comparisons across datasets. RESULTS: BRM v2.3 has the
      capability to query predicted miRNA targets from multiple databases, retrieve
      potential regulatory miRNAs for known genes, integrate experimentally derived
      miRNA and mRNA datasets, perform ortholog mapping across species, and retrieve
      annotation and cross-reference identifiers for an expanded number of species.
      Here we use BRM to show that developmental exposure of zebrafish to 30 uM
      nicotine from 6-48 hours post fertilization (hpf) results in behavioral
      hyperactivity in larval zebrafish and alteration of putative miRNA gene targets
      in whole embryos at developmental stages that encompass early neurogenesis. We
      show typical workflows for using BRM to integrate experimental zebrafish miRNA
      and mRNA microarray datasets with example retrievals for zebrafish, including
      pathway annotation and mapping to human ortholog. Functional analysis of
      differentially regulated (p<0.05) gene targets in BRM indicates that nicotine
      exposure disrupts genes involved in neurogenesis, possibly through misregulation
      of nicotine-sensitive miRNAs. CONCLUSIONS: BRM provides the ability to mine
      complex data for identification of candidate miRNAs or pathways that drive
      phenotypic outcome and, therefore, is a useful hypothesis generation tool for
      systems biology. The miRNA workflow in BRM allows for efficient processing of
      multiple miRNA and mRNA datasets in a single software environment with the added
      capability to interact with public data sources and visual analytic tools for HTP
      data analysis at a systems level. BRM is developed using JavaTM and other open
      source technologies for free distribution
      (http://www.sysbio.org/dataresources/brm.stm).

PMID- 23174016
TI  - A minimum price per unit of alcohol: a focus group study to investigate public
      opinion concerning UK government proposals to introduce new price controls to
      curb alcohol consumption.
AB  - BACKGROUND: UK drinkers regularly consume alcohol in excess of guideline limits.
      One reason for this may be the high availability of low-cost alcoholic beverages.
      The introduction of a minimum price per unit of alcohol policy has been proposed
      as a means to reduce UK alcohol consumption. However, there is little in-depth
      research investigating public attitudes and beliefs regarding a minimum pricing
      policy. The aim of the present research was to investigate people's attitudes and
      beliefs toward the introduction of a minimum price per unit of alcohol policy and
      their views on how the policy could be made acceptable to the general public.
      METHODS: Twenty-eight focus groups were conducted to gain in-depth data on
      attitudes, knowledge, and beliefs regarding the introduction of a minimum price
      per unit of alcohol policy. Participants (total N = 218) were asked to give their
      opinions about the policy, its possible outcomes, and how its introduction might
      be made more acceptable. Transcribed focus-group discussions were analysed for
      emergent themes using inductive thematic content analysis. RESULTS: Analysis
      indicated that participants' objections to a minimum price had three main themes:
      (1) scepticism of minimum pricing as an effective means to reduce harmful alcohol
      consumption; (2) a dislike of the policy for a number of reasons (e.g., it was
      perceived to 'punish' the moderate drinker); and (3) concern that the policy
      might create or exacerbate existing social problems. There was a general
      perception that the policy was aimed at 'problem' and underage drinkers.
      Participants expressed some qualified support for the policy but stated that it
      would only work as part of a wider campaign including other educational elements.
      CONCLUSIONS: There was little evidence to suggest that people would support the
      introduction of a minimum price per unit of alcohol policy. Scepticism about the
      effectiveness of the policy is likely to represent the most significant barrier
      to public support. Findings also suggest that clearer educational messages are
      needed to dispel misconceptions regarding the effectiveness of the policy and the
      introduction of the policy as part of a package of government initiatives to
      address excess alcohol consumption might be the best way to advance support for
      the policy.

PMID- 23174017
TI  - Assessing the potential effectiveness of food and beverage taxes and subsidies
      for improving public health: a systematic review of prices, demand and body
      weight outcomes.
AB  - Taxes and subsidies are increasingly being considered as potential policy
      instruments to incentivize consumers to improve their food and beverage
      consumption patterns and related health outcomes. This study provided a
      systematic review of recent U.S. studies on the price elasticity of demand for
      sugar-sweetened beverages (SSBs), fast food, and fruits and vegetables, as well
      as the direct associations of prices/taxes with body weight outcomes. Based on
      the recent literature, the price elasticity of demand for SSBs, fast food, fruits
      and vegetables was estimated to be -1.21, -0.52, -0.49 and -0.48, respectively.
      The studies that linked soda taxes to weight outcomes showed minimal impacts on
      weight; however, they were based on existing state-level sales taxes that were
      relatively low. Higher fast-food prices were associated with lower weight
      outcomes particularly among adolescents, suggesting that raising prices would
      potentially impact weight outcomes. Lower fruit and vegetable prices were
      generally found to be associated with lower body weight outcomes among both low
      income children and adults, suggesting that subsidies that would reduce the cost
      of fruits and vegetables for lower-socioeconomic populations may be effective in
      reducing obesity. Pricing instruments should continue to be considered and
      evaluated as potential policy instruments to address public health risks.

PMID- 23174018
TI  - IL-1beta promotes stemness and invasiveness of colon cancer cells through Zeb1
      activation.
AB  - BACKGROUND: IL-1beta is a pleiotropic pro-inflammatory cytokine and its up
      regulation is closely associated with various cancers including gastrointestinal
      tumors. However, it remains unclear how IL-1beta may contribute to the initiation
      and development of these inflammation-associated cancers. Here we investigated
      the role of IL-1beta in colon cancer stem cell (CSC) development. METHODS: Using
      self-renewal assay, soft-agar assay, invasion assay, real-time PCR analysis,
      immunoblot assay and shRNA knockdown, we determined the effects of IL-1beta on
      cancer stem cell development and epithelial-mesenchymal transition (EMT) in human
      primary colon cancer cells and colon cancer cell line HCT-116. RESULTS: We found
      that IL-1beta can increase sphere-forming capability of colon cancer cells in
      serum-free medium. IL-1beta-induced spheres displayed an up-regulation of
      stemness factor genes (Bmi1 and Nestin) and increased drug resistance, hallmarks
      of CSCs. Importantly, expression of EMT activator Zeb1 was increased in IL-1beta
      induced spheres, indicating that there might be a close association between EMT
      and IL-1beta-induced CSC self-renewal. Indeed, IL-1beta treatment led to EMT of
      colon cancer cells with loss of E-cadherin, up-regulation of Zeb1, and gain of
      the mesenchymal phenotype. Furthermore, shRNA-mediated knockdown of Zeb1 in HCT
      116 cells reversed IL-1beta-induced EMT and stem cell formation. CONCLUSION: Our
      findings indicate that IL-1beta may promote colon tumor growth and invasion
      through activation of CSC self-renewal and EMT, and Zeb1 plays a critical role in
      these two processes. Thus, IL-1beta and Zeb1 might be new therapeutic targets
      against colon cancer stem cells.

PMID- 23174020
TI  - Treatment failure in osteoporosis.

PMID- 23174019
TI  - Good news for HRT--what next?

PMID- 23174022
TI  - High-throughput sequencing of the melanoma genome.
AB  - Next-generation sequencing technologies are now common for whole-genome, whole
      exome and whole-transcriptome sequencing (RNA-seq) of tumors to identify point
      mutations, structural or copy number alterations and changes in gene expression.
      A substantial number of studies have already been performed for melanoma. One
      study analysed eight melanoma cell lines with RNA-Seq technology and identified
      11 novel melanoma gene fusions. Whole-exome sequencing of seven melanoma cell
      lines identified overlapping gain of function mutations in MAP2K1 (MEK1) and
      MAP2K2 (MEK2) genes. Integrative sequencing of cutaneous melanoma metastases
      using different sequencing platforms revealed a new somatic point mutation in
      HRAS and a structural rearrangement affecting CDKN2C (a CDK4 inhibitor). These
      latter sequencing-based discoveries may be used to motivate the inclusion of the
      affected patients into clinical trials with specific signalling pathway
      inhibitors. Taken together, we are at the beginning of an era with new sequencing
      technologies providing a more comprehensive view of cancer mutational landscapes
      and hereby a better understanding of their pathogenesis. This will also open
      interesting perspectives for new treatment approaches and clinical trial designs.

PMID- 23174021
TI  - Rapid resolution of an acute subdural hematoma by increasing the shunt valve
      pressure in a 63-year-old man with normal-pressure hydrocephalus with a
      ventriculoperitoneal shunt: a case report and literature review.
AB  - INTRODUCTION: Symptomatic subdural hematoma development is a constant concern
      for patients who have undergone cerebrospinal fluid shunting procedures to
      relieve symptoms related to normal-pressure hydrocephalus. Acute subdural
      hematomas are of particular concern in these patients as even minor head trauma
      may result in subdural hematoma formation. The presence of a ventricular shunt
      facilitates further expansion of the subdural hematoma and often necessitates
      surgical treatment, including subdural hematoma evacuation and shunt ligation.
      CASE PRESENTATION: We present the case of a 63-year-old North American Caucasian
      man with normal-pressure hydrocephalus with an adjustable valve
      ventriculoperitoneal shunt who developed an acute subdural hematoma after
      sustaining head trauma. Conservative treatment was favored over operative
      evacuation because our patient was neurologically intact, but simple observation
      was considered to be too high risk in the setting of a low-pressure
      ventriculoperitoneal shunt. Thus, the valve setting on the ventriculoperitoneal
      shunt was increased to its maximum pressure setting in order to reduce flow
      through the shunt and to mildly increase intracranial pressure in an attempt to
      tamponade any active bleeding and limit hematoma expansion. A repeat computed
      tomography scan of the head six days after the valve adjustment revealed complete
      resolution of the acute subdural hematoma. At this time, the valve pressure was
      reduced to its original setting to treat symptoms of normal-pressure
      hydrocephalus. CONCLUSIONS: Programmable shunt valves afford the option for non
      operative management of acute subdural hematoma in patients with ventricular
      shunts for normal-pressure hydrocephalus. As illustrated in this case report,
      increasing the shunt valve pressure may result in rapid resolution of the acute
      subdural hematoma in some patients.

PMID- 23174023
TI  - Combination of thermographic and ultrasonographic assessments for early detection
      of deep tissue injury.
AB  - Early detection and intervention of deep tissue injury are important to lead good
      outcome. Although the efficiency of ultrasonographic assessment of deep tissue
      injury has been reported previously, it requires a certain level of skill for
      accurate assessment. In this study, we present an investigation of the
      combination of thermographic and ultrasonographic assessments for early detection
      of deep tissue injury. We retrospectively reviewed 28 early-stage pressure ulcers
      (21 patients) presenting at the University of Tokyo Hospital between April 2009
      and February 2010, surveying the associated thermographic and ultrasonographic
      findings. The wound temperature patterns were divided into low, even and high
      compared with the surrounding skin. Ultrasonographic findings were classified
      into unclear layer structure, hypoechoic lesion, discontinuous fascia and
      heterogeneous hypoechoic area. All 13 ulcers that were associated with low
      temperature showed good outcome; three ulcers had even temperatures and 12 ulcers
      showed high temperature on thermographic assessment. The two deep tissue injuries
      were rated high on thermographic assessment and showed heterogeneous hypoechoic
      area findings on ultrasonographic assessment. No non-deep tissue injury lesion
      was associated with these two findings simultaneously. The combination of
      thermographic and ultrasonographic assessments is expected to increase the
      accuracy of the early detection of deep tissue injuries. 

PMID- 23174024
TI  - Sustainability of healthcare innovations (SUSHI): long term effects of two
      implemented surgical care programmes (protocol).
AB  - BACKGROUND: Two healthcare innovations were successfully implemented using
      different implementation strategies. First, a Short Stay Programme for breast
      cancer surgery (MaDO) was implemented in four early adopter hospitals, using a
      hospital-tailored implementation strategy. Second, the Enhanced Recovery After
      Surgery (ERAS) programme for colonic surgery was implemented in 33 Dutch
      hospitals, using a generic breakthrough implementation strategy. Both strategies
      resulted in a shorter hospital length of stay without a decrease in quality of
      care. Currently, it is unclear to what extent these innovative programmes and
      their results have been sustained three to five years following implementation.
      The aim of the sustainability of healthcare innovations (SUSHI) study is to
      analyse sustainability and its determinants using two implementation cases.
      METHODS: This observational study uses a mixed methods approach. The study will
      be performed in 14 hospitals in the Netherlands, from November 2010. For both
      implementation cases, the programme aspects and the effects will be evaluated by
      means of a follow-up measurement in 160 patients who underwent breast cancer
      surgery and 300 patients who underwent colonic surgery. A policy cost
      effectiveness analysis from a societal perspective will be performed
      prospectively for the Short Stay Programme for breast cancer surgery in 160
      patients. To study determinants of sustainability key professionals in the
      multidisciplinary care processes and implementation change agents will be
      interviewed using semi-structured interviews. DISCUSSION: The concept of
      sustainability is not commonly studied in implementation science. The SUSHI study
      will provide insight in to what extent the short-term implementation benefits
      have been maintained and in the determinants of long-term continuation of
      programme activities.

PMID- 23174025
TI  - Persistent infectious diseases say - IDO. Role of indoleamine-2,3-dioxygenase in
      disease pathogenesis and implications for therapy.
AB  - Indoleamine-2,3-dioxygenase (IDO) is an enzyme that catabolises tryptophan - an
      essential amino acid critical for T cell proliferation. Initially recognized as a
      first line of host defense against infectious pathogens, IDO has been
      subsequently identified as an important immune-regulator inhibiting T-cell
      responses and promoting immune tolerance. Research over the past few years has
      demonstrated a crucial role for IDO in the pathogenesis of persistent infections
      that place an enormous burden on public health. In this review, we summarize
      current knowledge about IDO's role in causing pathogen persistence and
      progression to clinical disease. We conclude with a perspective on the potential
      benefits and risks of therapeutic IDO manipulation.

PMID- 23174026
TI  - Transradial approach for cardiovascular interventions and its implications for
      hemodialysis vascular access.
AB  - Because of its advantages, the transradial approach for cardiovascular
      interventions has gained significant popularity. However, this approach can be
      associated with radial artery thrombosis and occlusion. The complication
      generates a major concern for its potential impact on the future creation of an
      arteriovenous hemodialysis access. The issue gains more importance as a
      significant number of patients with cardiovascular disease suffer from underlying
      chronic kidney disease (CKD) and might need an arteriovenous access for
      hemodialysis therapy. In this context, the preservation of the arterial system is
      of equal importance to the frequently highlighted venous conservation for the
      successful creation of an arteriovenous access. It is for this reason that the
      Fistula First Breakthrough Initiative recommends avoiding the use of the radial
      artery for performing percutaneous interventions in patients with advanced CKD.
      Furthermore, there is scarce clinical data and publication regarding the impact
      of transradial approach on hemodialysis access. Is it possible to utilize the
      potential benefits and minimize the potential risks of transradial approach in
      chronic kidney disease patients? On the basis of current knowledge, this review
      discusses related issues of transradial approach to raise awareness and
      understanding, which are essential to proper caring of CKD patients undergoing
      cardiovascular interventions.

PMID- 23174027
TI  - Spontaneous generation of reactive oxygen species and effect on motility and
      fertilizability of sea urchin spermatozoa.
AB  - We investigated the generation of reactive oxygen species (ROS) by spermatozoa in
      two species of sea urchin. ROS generation was accompanied by the initiation of
      motility and respiration and influenced the motility and fertilizability of
      spermatozoa. The sea urchin performs external fertilization in aerobic seawater.
      Sperm motility was initiated after spawning through Na+/H+ exchange. ROS
      generation was dependent on the respiration and sperm concentration and its
      generation was first observed at initiation of motility, via activation of
      respiration through ATP/ADP transport. The ROS generation rate increased at
      higher dilution ratios of spermatozoa, in a manner that was synchronous with the
      respiratory rate. This phenomenon resembled the previously defined 'sperm
      dilution effect' on respiration. The loss of motility and fertilizability was
      induced not only by treatment with hydrogen peroxide but also by sperm dilution.
      Storage of spermatozoa with a higher dilution ratio also accelerated the decrease
      in fertilizability. Thus, optimum sea urchin fertilizability is maintained by
      storage of undiluted spermatozoa on ice, in order to minimize oxidative stress
      and to maximize longevity.

PMID- 23174028
TI  - Feasibility of inguinal hernioplasty under local anaesthesia in elderly patients.
AB  - BACKGROUND: The aim of this study is to evaluate the feasibility and the safety
      of hernioplasty under local anaesthesia in elderly patients with significant
      comorbidity. METHODS: A total of 218 patients underwent inguinal hernia repair
      with mesh between June 2009 and July 2012. Presence of comorbid conditions and
      complications were compared between patients younger and older than 70 years.
      RESULTS: Hernia repair in older patients were more likely associated with
      comorbid conditions than in their younger counterparts ( hypertension: 25% vs
      8.16%; cardiovascular diseases: 50% vs 22%; benign prostatic hypertrophy 60% vs
      30%). The most common postoperative complications in both groups were recurrence,
      wound infection, urinary retention. There was a slightly higher rate of
      complication in elderly group. CONCLUSIONS: Inguinal hernia repair with local
      anaesthesia is quite safe and results in a good success rate in elderly patients
      despite a higher rate of comorbidity typical of this kind of patient.

PMID- 23174030
TI  - Towards HCV extinction with modern HCV treatment? "Yes we can!".

PMID- 23174031
TI  - The relationship between carotid intima-media thickness and endogenous androgens
      in young women with polycystic ovary syndrome in Taiwan.
AB  - Polycystic ovary syndrome (PCOS) is a common and complex female endocrinopathy
      that is associated with multiple vascular risk factors. Our objective was to
      investigate the relationship between carotid intima-media thickness (CIMT) and
      endogenous androgens in young Taiwanese-Chinese women with PCOS. We measured CIMT
      with B-mode ultrasound in 42 young PCOS patients and 43 controls. Atherosclerosis
      associated profiles and endocrinological parameters were also measured. The
      results showed that although Taiwanese-Chinese PCOS patients tend to possess more
      risk factors for atherosclerosis than controls, there was no evidence to support
      that they have a greater CIMT at this age. Furthermore, androstenedione appears
      to be inversely associated with CIMT.

PMID- 23174029
TI  - The role of selection in driving landscape genomic structure of the waterflea
      Daphnia magna.
AB  - The combined analysis of neutral and adaptive genetic variation is crucial to
      reconstruct the processes driving population genetic structure in the wild.
      However, such combined analysis is challenging because of the complex interaction
      among neutral and selective processes in the landscape. Overcoming this level of
      complexity requires an unbiased search for the evidence of selection in the
      genomes of populations sampled from their natural habitats and the identification
      of demographic processes that lead to present-day populations' genetic structure.
      Ecological model species with a suite of genomic tools and well-understood
      ecologies are best suited to resolve this complexity and elucidate the role of
      selective and demographic processes in the landscape genomic structure of natural
      populations. Here we investigate the water flea Daphnia magna, an emerging model
      system in genomics and a renowned ecological model system. We infer past and
      recent demographic processes by contrasting patterns of local and regional
      neutral genetic diversity at markers with different mutation rates. We assess the
      role of the environment in driving genetic variation in our study system by
      identifying correlates between biotic and abiotic variables naturally occurring
      in the landscape and patterns of neutral and adaptive genetic variation. Our
      results indicate that selection plays a major role in determining the population
      genomic structure of D. magna. First, environmental selection directly impacts
      genetic variation at loci hitchhiking with genes under selection. Second,
      priority effects enhanced by local genetic adaptation (cf. monopolization) affect
      neutral genetic variation by reducing gene flow among populations and genetic
      diversity within populations.

PMID- 23174032
TI  - Isolation and phylogenetic analysis of orf virus from the sheep herd outbreak in
      northeast China.
AB  - BACKGROUND: Orf is a zoonotic and epitheliotrophic contagious disease that mainly
      affects sheep, goats, wild ruminants, and humans with a worldwide distribution.
      To date, there is little information on the characterization of ORFV strains that
      are endemic in Mainland China. In addition, the relationship between the severity
      of disease and the molecular profile of ORFV strains has not been fully
      elucidated. RESULTS: From the recent outbreak of a sheep herd in Nongan,
      northeast of China, the novel orf virus (ORFV) strain NA1/11 was successfully
      isolated. Western blot analysis indicated that the NA1/11 strain cross reacts
      with monoclonal antibody A3 and infected sheep ORFV antiserum. The purified
      virions revealed the typical ovoid shape when observed by atomic force
      microscopy. To determine the genetic characteristics of the NA1/11 strain, the
      sequences of ORFV011 (B2L), ORFV059 (F1L), ORFV109, ORFV110 and ORFv132 (VEGF)
      genes were amplified and compared with reference parapoxvirus strains. Non-metric
      multidimensional scaling (nMDS) was performed to analyze the nucleotide
      similarities between different ORFV strains. CONCLUSIONS: Phylogenetic analysis
      based on ORFV 011 nucleotide sequences showed that the NA1/11strain was closely
      related to Xinjiang and Gansu strains. ORFV110 and ORFV132 genes are highly
      variable. The results revealed that precise phylogenetic analysis might provide
      evidence for genetic variation and movement of circulating ORFV strains in
      Northeast China. In addition, nMDS analysis showed that geographic isolation and
      animal host are likely major factors resulting in genetic differences between
      ORFV strains.

PMID- 23174034
TI  - Borderline sebaceous neoplasm in a renal transplant patient without Muir-Torre
      syndrome.
AB  - Borderline sebaceous neoplasms are rare tumors that can be challenging to
      diagnose because of their admixture of histopathologic features. Most such tumors
      have been described in patients with Muir-Torre syndrome (MTS). We report the
      case of an immunosuppressed, 82-year-old African-American woman without MTS who
      developed a rapidly growing lesion on the left cheek. Histopathology revealed a
      borderline sebaceous neoplasm with predominant features of sebaceous adenoma and
      with focal features raising concern for the possibility of an evolving, well
      differentiated, low-grade sebaceous carcinoma with a high mitotic index. In the
      setting of immunosuppression, borderline sebaceous neoplasms may occur outside of
      MTS; careful evaluation and conservative treatment are recommended in managing
      such tumors. 

PMID- 23174033
TI  - Pharmacological insights into the role of P2X4 receptors in behavioural
      regulation: lessons from ivermectin.
AB  - Purinergic ionotropic P2X receptors are a family of cation-permeable channels
      that bind extracellular adenosine 5'-triphosphate. In particular, convergent
      lines of evidence have recently highlighted P2X(4) receptors as a potentially
      critical target in the regulation of multiple nervous and behavioural functions,
      including pain, neuroendocrine regulation and hippocampal plasticity.
      Nevertheless, the role of the P2X(4) receptor in behavioural organization remains
      poorly investigated. To study the effects of P2X(4) activation, we tested the
      acute effects of its potent positive allosteric modulator ivermectin (IVM, 2.5-10
      mg/kg i.p.) on a broad set of paradigms capturing complementary aspects of
      perceptual, emotional and cognitive regulation in mice. In a novel open field,
      IVM did not induce significant changes in locomotor activity, but increased the
      time spent in the peripheral zone. In contrast, IVM produced anxiolytic-like
      effects in the elevated plus maze and marble burying tasks, as well as depression
      like behaviours in the tail-suspension and forced swim tests. The agent induced
      no significant behavioural changes in the conditioned place preference test and
      in the novel object recognition task. Finally, the drug induced a dose-dependent
      decrease in sensorimotor gating, as assessed by pre-pulse inhibition (PPI) of the
      acoustic startle reflex. In P2X(4) knockout mice, the effects of IVM in the open
      field and elevated plus maze were similar to those observed in wild type mice;
      conversely, the drug significantly increased startle amplitude and failed to
      reduce PPI. Taken together, these results suggest that P2X(4) receptors may play
      a role in the regulation of sensorimotor gating.

PMID- 23174035
TI  - Assessment of the thrombin generation assay in haemophilia: comparative study
      between fresh and frozen platelet-rich plasma.
AB  - The severity of haemophilia A has traditionally been classified by the dosage of
      factor VIII (FVIII) by one-step coagulation tests. However, an homogeneous group
      of patients with similar FVIII levels show clinical heterogeneity and 10-15% of
      the patients classified as severe haemophilia do not have a severe bleeding
      phenotype. Traditional tests used for measuring FVIII are not capable of
      detecting other prohaemorrhagic or prothrombotic factors. Global tests as the
      thrombin generation assay (TGA) may detect these haemostatic factors. So TGA may
      be an additional tool for classifying the actual severity of haemophilia. Our
      group is carrying out correlation tests between FVIII and TGA in platelet-poor
      and -rich plasmas (PPP and PRP, respectively). PRP has the inconvenience that
      must be done freshly soon after blood extraction. Our aim is to study the
      differences between TGA performed with fresh and frozen PRP and PPP and its
      implementation in multicenter studies. We included 70 patients with severe
      haemophilia A in prophylactic treatment. Venous blood drawing was obtained prior
      to administration of FVIII, at the trough levels. FVIII measurement and TGA were
      performed in fresh and frozen PRP and PPP. The platelet absence caused a
      significant decrease in TGA although PPP and PRP correlated well. Frozen samples
      gave different results in PPP, but there were no significant differences between
      fresh and frozen PRP. This fact enables using frozen PRP in multicenter studies
      with a TGA-specialized laboratory for reclassifying haemophilia severity and for
      pharmacokinetic studies with TGA.

PMID- 23174036
TI  - Core Hunter II: fast core subset selection based on multiple genetic diversity
      measures using Mixed Replica search.
AB  - BACKGROUND: Sampling core subsets from genetic resources while maintaining as
      much as possible the genetic diversity of the original collection is an important
      but computationally complex task for gene bank managers. The Core Hunter computer
      program was developed as a tool to generate such subsets based on multiple
      genetic measures, including both distance measures and allelic diversity indices.
      At first we investigate the effect of minimum (instead of the default mean)
      distance measures on the performance of Core Hunter. Secondly, we try to gain
      more insight into the performance of the original Core Hunter search algorithm
      through comparison with several other heuristics working with several realistic
      datasets of varying size and allelic composition. Finally, we propose a new
      algorithm (Mixed Replica search) for Core Hunter II with the aim of improving the
      diversity of the constructed core sets and their corresponding generation times.
      RESULTS: Our results show that the introduction of minimum distance measures
      leads to core sets in which all accessions are sufficiently distant from each
      other, which was not always obtained when optimizing mean distance alone.
      Comparison of the original Core Hunter algorithm, Replica Exchange Monte Carlo
      (REMC), with simpler heuristics shows that the simpler algorithms often give very
      good results but with lower runtimes than REMC. However, the performance of the
      simpler algorithms is slightly worse than REMC under lower sampling intensities
      and some heuristics clearly struggle with minimum distance measures. In
      comparison the new advanced Mixed Replica search algorithm (MixRep), which uses
      heterogeneous replicas, was able to sample core sets with equal or higher
      diversity scores than REMC and the simpler heuristics, often using less
      computation time than REMC. CONCLUSION: The REMC search algorithm used in the
      original Core Hunter computer program performs well, sometimes leading to
      slightly better results than some of the simpler methods, although it doesn't
      always give the best results. By switching to the new Mixed Replica algorithm
      overall results and runtimes can be significantly improved. Finally we recommend
      including minimum distance measures in the objective function when looking for
      core sets in which all accessions are sufficiently distant from each other. Core
      Hunter II is freely available as an open source project at
      http://www.corehunter.org.

PMID- 23174037
TI  - Experimental support of the stress-gradient hypothesis in herbivore-herbivore
      interactions.
AB  - The stress-gradient hypothesis (SGH) postulates an increase in the frequency of
      positive species interactions at increasing amounts of stress. While the SGH has
      been extensively tested in plant-plant interactions along abiotic stresses, it
      remains unclear whether this hypothesis could apply to higher trophic levels,
      such as herbivores, along biotic stress gradients. To address this issue, we
      investigated how the interaction between two potato herbivores may change along a
      stress gradient created by an assortment of potato varieties with different tuber
      palatability. We used a tuber resistance trait as a measure for biotic stress and
      one herbivore as the facilitator to gain access to the tuber of the other
      herbivore. Our experiment revealed a switch from neutral to positive interactions
      with increasing stress, confirming for the first time the predictions of the SGH
      for herbivores. Moreover, the intensity of facilitation decreased at high stress
      levels, suggesting that benefits by the facilitating species were dampened in the
      most stressful environment. In view of the ubiquitous role played by positive
      interactions among herbivores, broadening our search image for facilitative
      effects among other plant enemies will allow a better awareness of the importance
      of the SGH in structuring plant communities.

PMID- 23174038
TI  - Ethics in EMS and disaster research.

PMID- 23174039
TI  - Development of a decision framework for establishing a health register following
      a major incident.
AB  - INTRODUCTION: Health registers have been established in the United Kingdom (UK)
      and elsewhere following mass exposure to novel agents or known agents, but there
      is no consensus on the criteria for establishing such registers. OBJECTIVE: This
      study aimed to develop a decision framework to assess the need for establishing a
      health register for major chemical, biological, radiological, and nuclear (CBRN)
      incidents. METHODS: The study comprised three stages. In the first stage, the
      study team prepared a list of potential criteria that may be used to assess the
      need for setting up a health register based on literature review and personal
      experiences in previous incidents. In the second stage, the potential criteria
      were evaluated in two Delphi rounds involving experts and key decision makers
      from the UK Health Protection Agency (HPA) and academic organizations. In the
      final stage, the criteria were converted into a decision framework, and its
      utility was tested using four fictional scenarios. RESULTS: A total of 11
      statements were proposed by the study group. These criteria were revised
      following feedback from 16 experts in the first Delphi round. All 11 statements
      achieved consensus at the end of the second Delphi round. Pilot testing of the
      agreed criteria on four fictional scenarios confirmed validity and reliability
      for use in the decision process. CONCLUSIONS: A decision framework to assess the
      need for setting up a health register after a major incident was agreed upon and
      tested using fictional scenarios. Further areas of work for practical
      implementation of the criteria and related planning for systems and protocols
      have been identified.

PMID- 23174040
TI  - Minimum data set for mass-gathering health research and evaluation: a discussion
      paper.
AB  - This paper discusses the need for consistency in mass-gathering data collection
      and biomedical reporting. Mass gatherings occur frequently throughout the world,
      and having an understanding of the complexities of mass gatherings is important
      to inform health services about the possible required health resources. Factors
      within the environmental, psychosocial and biomedical domains influence the usage
      of health services at mass gatherings. The biomedical domain includes the
      categorization of presenting injury or illness, and rates such as patient
      presentation rate, transferred to hospital rate and referred to hospital rate.
      These rates provide insight into the usage of onsite health services, prehospital
      ambulance services. and hospital emergency department services. Within the
      literature, these rates are reported in a manner that is varied, haphazard and
      author dependent. This paper proposes moving away from an author-dependent
      practice of collection and reporting of data. An expert consensus approach is
      proposed as a means of further developing mass-gathering theory and moving beyond
      the current situation of reporting on individual case studies. To achieve this, a
      minimum data set with a data dictionary is proposed in an effort to generate
      conversation about a possible agreed minimum amount and type of information that
      should be collected consistently for research and evaluation at mass gatherings.
      Finally, this paper outlines future opportunities that will emerge from the
      consistent collection and reporting of mass-gathering data, including the
      possibility for meta-analysis, comparison of events across societies and modeling
      of various rates to inform health services.

PMID- 23174041
TI  - Multiple patients with carbon monoxide toxicity from water-pipe smoking.
AB  - This case report describes carbon monoxide toxicity from prolonged shisha (water
      pipe) smoking. The evidence base for the source and pathway of toxicity is
      discussed. This practice has been increasing in the UK in recent years, and
      emergency physicians need to be aware of the high levels of CO, with the
      consequent risk of clinical poisoning from water-pipe smoking.

PMID- 23174042
TI  - Design of a model to predict surge capacity bottlenecks for burn mass casualties
      at a large academic medical center.
AB  - OBJECTIVES: To design and test a model to predict surge capacity bottlenecks at a
      large academic medical center in response to a mass-casualty incident (MCI)
      involving multiple burn victims. METHODS: Using the simulation software ProModel,
      a model of patient flow and anticipated resource use, according to principles of
      disaster management, was developed based upon historical data from the University
      Hospital of the University of Michigan Health System. Model inputs included: (a)
      age and weight distribution for casualties, and distribution of size and depth of
      burns; (b) rate of arrival of casualties to the hospital, and triage to ward or
      critical care settings; (c) eligibility for early discharge of non-MCI inpatients
      at time of MCI; (d) baseline occupancy of intensive care unit (ICU), surgical
      step-down, and ward; (e) staff availability-number of physicians, nurses, and
      respiratory therapists, and the expected ratio of each group to patients; (f)
      floor and operating room resources-anticipating the need for mechanical
      ventilators, burn care and surgical resources, blood products, and intravenous
      fluids; (g) average hospital length of stay and mortality rate for patients with
      inhalation injury and different size burns; and (h) average number of times that
      different size burns undergo surgery. Key model outputs include time to
      bottleneck for each limiting resource and average waiting time to hospital bed
      availability. RESULTS: Given base-case model assumptions (including 100 mass
      casualties with an inter-arrival rate to the hospital of one patient every three
      minutes), hospital utilization is constrained within the first 120 minutes to 21
      casualties, due to the limited number of beds. The first bottleneck is
      attributable to exhausting critical care beds, followed by floor beds. Given this
      limitation in number of patients, the temporal order of the ensuing bottlenecks
      is as follows: Lactated Ringer's solution (4 h), silver sulfadiazine/Silvadene (6
      h), albumin (48 h), thrombin topical (72 h), type AB packed red blood cells (76
      h), silver dressing/Acticoat (100 h), bismuth tribromophenate/Xeroform (102 h),
      and gauze bandage rolls/Kerlix (168 h). The following items do not precipitate a
      bottleneck: ventilators, topical epinephrine, staplers, foams, antimicrobial non
      adherent dressing/Telfa types A, B, or O blood. Nurse, respiratory therapist, and
      physician staffing does not induce bottlenecks. CONCLUSIONS: This model, and
      similar models for non-burn-related MCIs, can serve as a real-time estimation and
      management tool for hospital capacity in the setting of MCIs, and can inform
      supply decision support for disaster management.

PMID- 23174043
TI  - Predicting the spatio-temporal distribution of Culicoides imicola in Sardinia
      using a discrete-time population model.
AB  - BACKGROUND: Culicoides imicola KIEFFER, 1913 (Diptera: Ceratopogonidae) is the
      principal vector of Bluetongue disease in the Mediterranean basin, Africa and
      Asia. Previous studies have identified a range of eco-climatic variables
      associated with the distribution of C. imicola, and these relationships have been
      used to predict the large-scale distribution of the vector. However, these
      studies are not temporally-explicit and can not be used to predict the
      seasonality in C. imicola abundances. Between 2001 and 2006, longitudinal
      entomological surveillance was carried out throughout Italy, and provided a
      comprehensive spatio-temporal dataset of C. imicola catches in Onderstepoort-type
      black-light traps, in particular in Sardinia where the species is considered
      endemic. METHODS: We built a dynamic model that allows describing the effect of
      eco-climatic indicators on the monthly abundances of C. imicola in Sardinia.
      Model precision and accuracy were evaluated according to the influence of process
      and observation errors. RESULTS: A first-order autoregressive cofactor, a digital
      elevation model and MODIS Land Surface Temperature (LST)/or temperatures acquired
      from weather stations explained ~77% of the variability encountered in the
      samplings carried out in 9 sites during 6 years. Incorporating Normalized
      Difference Vegetation Index (NDVI) or rainfall did not increase the model's
      predictive capacity. On average, dynamics simulations showed good accuracy
      (predicted vs. observed r corr = 0.9). Although the model did not always
      reproduce the absolute levels of monthly abundances peaks, it succeeded in
      reproducing the seasonality in population level and allowed identifying the
      periods of low abundances and with no apparent activity. On that basis, we mapped
      C. imicola monthly distribution over the entire Sardinian region. CONCLUSIONS:
      This study demonstrated prospects for modelling data arising from Culicoides
      longitudinal entomological surveillance. The framework explicitly incorporates
      the influence of eco-climatic factors on population growth rates and accounts for
      observation and process errors. Upon validation, such a model could be used to
      predict monthly population abundances on the basis of environmental conditions,
      and hence can potentially reduce the amount of entomological surveillance.

PMID- 23174044
TI  - Assessment of psychosocial variables by parents of youth with type 1 diabetes
      mellitus.
AB  - PURPOSE: To evaluate the impact of type 1 diabetes (T1D) on family functioning
      and child-rearing practices from parents' point of view, to assess parents'
      health-related quality of life and to explore the relations between psychosocial
      variables and diabetes care outcomes in youth with diabetes. METHODS: This
      research was part of the cross-sectional multicenter Brazilian Type 1 Diabetes
      Study, conducted between December 2008 and December 2010 in 28 public clinics of
      20 cities across four Brazilian geographical regions. Psychosocial questions were
      addressed to 1,079 parents of patients with T1D through an interview (89.3%
      mothers, 52.5% Caucasians, 38.6 +/- 7.6 years old). Overall, 72.5% of the
      families were from low or very low socioeconomic levels. Parents were also
      submitted to health-related quality of life instruments (EQ-5D+EQ-VAS). Clinical
      data from the last medical appointment were collected by a physician using
      standardized chart review forms. The demographic, educational and socioeconomic
      profiles were also obtained and HbA1c levels registered. RESULTS: Discomfort and
      anxiety/depression were the main complaints in EQ-5D, and were significantly more
      frequent in mothers (37.3% and 53.4%, respectively) than in fathers (25.7% and
      32.7%, respectively). The mother was the only parent involved in diabetes care in
      50.5% of the cases. The majority of parents (78.5%) mentioned changes in family
      functioning after the diagnosis, although they neither treated their diabetic
      children differently from the others (76.3%), nor set prohibitions (69.1%) due to
      diabetes. The majority was worried about diabetes complications (96.4%) and felt
      overwhelmed by diabetes care (62.8%). Parents report of overwhelming was
      significantly associated with anxiety/depression, as measured by the EQ-5D
      questionnaire. Less than half of the patients had already slept over, and the
      permission to do it increased as a function of children's age. Nearly half of the
      parents (52%) admitted to experiencing difficulties in setting limits for their
      children/adolescents. HbA1c levels in patients from this group (9.7 +/- 2.5%)
      were significantly higher than those of children/adolescents whose parents
      reported no difficulties towards limit-setting (8.8 +/- 2.1%). Parents whose
      children/adolescents reported the occurrence of hypoglycemic episodes in the last
      month complained significantly more about anxiety/depression (55.1%) than parents
      from patients who did not report it (45.7%). Also a significantly greater
      proportion of parents whose children/adolescents had been hospitalized due to
      hyperglycemia reported anxiety /depression (58.7%) than those whose
      children/adolescents had not been hospitalized (49.8%). CONCLUSIONS: After the
      diagnosis of T1D, the lifestyle of all family members changes, what interferes
      with their quality of life. Mothers are still the primary caregivers for
      children/adolescents with diabetes. Difficulty to set limits for
      children/adolescents may be a risk for poor metabolic control. The study
      demonstrates the importance of family context in the adjustment of young patients
      to T1D. The specific needs of T1D patients and their impact on a family routine
      must be considered for future improvement on therapy elements and strategies.

PMID- 23174045
TI  - Differential effects of topical corticosteroid and calcineurin inhibitor on the
      epidermal tight junction.
AB  - Tight junction (TJ) is one of the functional barriers present in the skin.
      Although topical corticosteroids and calcineurin inhibitors are used widely for
      atopic dermatitis, the effect of these agents on TJs has not been reported. We
      investigated the structural changes of TJs in mice skin after application of
      0.05% clobetasol propionate or 0.1% tacrolimus ointment for 10 days. Clobetasol
      caused epidermal thinning and decreased collagen density. Basal transepidermal
      water loss was significantly increased in clobetasol-treated versus vehicle- or
      tacrolimus-treated skin. Confocal immunofluorescence showed that clobetasol
      altered the structure of claudin-1,-4 and occludin. Tacrolimus also caused
      morphological alteration of occludin. Western blot and real-time PCR revealed
      that clobetasol significantly decreased claudin-1,-4 and occludin, whereas
      tacrolimus did not significantly affect claudin-1 and -4 but downregulated
      occludin to a lesser extent compared to clobetasol. In conclusion, we suggest
      that downregulation of TJ proteins expression is another pathomechanism of
      corticosteroid-induced permeability barrier disruption.

PMID- 23174046
TI  - Are cosmetics safe?

PMID- 23174047
TI  - The tolerability profile of clindamycin 1%/benzoyl peroxide 5% gel vs. adapalene
      0.1%/benzoyl peroxide 2.5% gel for facial acne: results of a randomized, single
      blind, split-face study.
AB  - BACKGROUND: Topical combination therapy, such as that with fixed-dose
      clindamycin/benzoyl peroxide (BPO) or adapalene/BPO, is the recommended first
      line approach for the treatment of facial acne. AIMS: To compare the tolerability
      of clindamycin 1%/BPO 5% gel vs. adapalene 0.1% BPO 2.5% gel for the first 2
      weeks of treatment in patients with facial acne. PATIENTS/METHODS: Using a
      randomized, single-blind, split-face method, 48 patients with acne received both
      clindamycin/BPO and adapalene/BPO once daily for 2 weeks. The primary endpoint
      was investigator-assessed tolerability. Treatment efficacy, patient-assessed
      tolerability and satisfaction, and safety were also investigated. RESULTS: Forty
      five patients completed treatment. Investigator-rated scores for erythema,
      dryness, and peeling were significantly higher with adapalene/BPO than
      clindamycin/BPO. Patients rated clindamycin/BPO as significantly more tolerable
      than adapalene/BPO for redness, dryness, burning, itching, and scaling.
      Investigator Static Global Assessment scores and lesion counts improved with both
      products, with no significant difference between treatments. Patients' Global
      Change Assessment showed a statistically significant difference in favor of
      clindamycin/BPO at week 1, but not week 2. Overall, >80% of patients were
      "satisfied" or "very satisfied" with treatment at week 2, but 63% of patients
      stated that they preferred clindamycin/BPO. Both products were well tolerated,
      with no serious adverse events (AEs), but a post hoc analysis indicated that
      treatment-related AEs, including irritation, dryness and erythema, were
      significantly less common with clindamycin/BPO. CONCLUSIONS: Clindamycin/BPO had
      a better tolerability profile than adapalene/BPO during 2 weeks of split-face
      treatment. Treatment satisfaction was highest with clindamycin/BPO.

PMID- 23174048
TI  - Use of a neuromuscular electrical stimulation device for facial muscle toning: a
      randomized, controlled trial.
AB  - BACKGROUND: Age-related loss of muscle mass contributes to aging of the human
      face. AIMS: To evaluate the effects of a neuromuscular electrical stimulation
      (NMES) device on facial muscle tone and signs of facial aging in healthy women.
      PATIENTS/METHODS: One hundred and eight healthy women (mean age 43.7, range 32 to
      58-45 years) participated in this randomized, controlled, partially blinded
      study. Participants were randomized to 12 weeks' treatment with the NMES facial
      device (20 min/day, 5 days/week) or to a nonintervention control group.
      Participants could not alter fitness, diet or facial care routines during the
      study. Assessments included psychometric evaluations of facial appearance and
      assessor-blinded ultrasound measurements of the thickness of the zygomatic major
      muscle. RESULTS: Mean muscle thickness increased vs. baseline in the NMES group
      (18.6%) but not the control group. Between-group differences were significant at
      6 and 12 weeks (P = 0.05 and P = 0.0001). NMES users reported subjective
      improvements in facial attributes. The control group did not. In an overall
      evaluation, >=80% of NMES users reported improved firmness, tone and lift vs. <5%
      of the control group (P < 0.001). CONCLUSIONS: A 12-week course of facial NMES
      was associated with increased thickness of the zygomatic major muscle and
      subjective improvements in facial attributes.

PMID- 23174049
TI  - Phase IV study comparing incobotulinumtoxinA and onabotulinumtoxinA using a 1:1.5
      dose-conversion ratio for the treatment of glabellar frown lines.
AB  - BACKGROUND: IncobotulinumtoxinA and onabotulinumtoxinA are effective treatments
      for glabellar frown lines, and a dose of 20 U is recommended for both
      preparations. However, debate continues over using the same dosages of these
      products, although a 1:1 dose ratio has been proven in several head-to-head
      clinical trials in neurological and esthetic indications. OBJECTIVES: To
      investigate whether a 50% higher dose of onabotulinumtoxinA was nonsuperior to
      incobotulinumtoxinA in the treatment of glabellar frown lines in the short and
      long term. METHODS AND MATERIALS: Subjects aged 18-65 years with symmetrical
      moderate-to-severe glabellar frown lines (score: >=2 on a validated Merz 5-point
      scale) at maximum frown were enrolled. Corrugator muscles on both sides were
      treated with two injections of either 4 U incobotulinumtoxinA or 6 U
      onabotulinumtoxinA (equivalent to 20 and 30 U, respectively, if corrugator
      muscles on both sides and the procerus are treated) allowing intra-individual
      comparison. Glabellar frown line severity was assessed from standardized
      photographs every 4 weeks for 4 months and, in a subset of subjects, for up to 6
      months posttreatment. The primary efficacy endpoint was the percentage of
      subjects with an improvement of >=1 point on the 5-point scale at week 4.
      Nonsuperiority was assessed by comparing the response rates of each product.
      RESULTS: Nonsuperiority of a 50% higher dose of onabotulinumtoxinA to that of
      incobotulinumtoxinA was confirmed at 4 weeks, 4 months, and 6 months
      posttreatment. CONCLUSION: There is generally no reason to increase the dose of
      either incobotulinumtoxinA or onabotulinumtoxinA above the 20 U recommended for
      glabellar frown lines.

PMID- 23174050
TI  - SIG1273: a new cosmetic functional ingredient to reduce blemishes and
      Propionibacterium acnes in acne prone skin.
AB  - BACKGROUND: Propionibacterium acnes is a major contributing factor to the
      inflammatory component of acne. The interaction of P. acnes with keratinocytes
      leads to an innate immune response via activation of toll-like receptors (TLR2,
      TLR4) resulting in the production and secretion of pro-inflammatory mediators.
      SIG1273, an isoprenylcysteine small molecule modulates inflammatory signaling
      pathways and kills P. acnes. SIG1273 represents a novel cosmetic functional
      ingredient that provides relief from blemishes in acne prone skin. OBJECTIVE: To
      assess the keratinocyte response and microbial growth of SIG1273 in vitro and
      evaluate the tolerability of SIG1273 gel applied topically in acne prone
      subjects. METHODS: For in vitro studies, human keratinocytes were exposed in
      culture to live P. acnes and peptidoglycan (PGN) to induce IL-8 production. P.
      acnes were cultured to determine minimal inhibitory concentration and minimal
      bactericidal concentration values. A total of 30 subjects were randomized in a
      double-blind controlled trial receiving 3% SIG1273 gel or vehicle for 6 weeks.
      Evaluation included inflammatory lesions, noninflammatory lesions,
      microcomedones, Sebutape scores, and P. acnes counts. RESULTS: In vitro studies
      demonstrate SIG1273 inhibits P. acnes-induced IL-8 production and inhibits P.
      acnes growth. SIG1273 gel was well tolerated with no signs of stinging, redness,
      or itching. Furthermore, improvement in some aspects of acne was observed in
      subjects applying SIG1273 gel, including inflammatory lesions, microcomedone
      counts and Sebutape scores. Facial scrubs taken to measure P. acnes colony
      forming units showed those applying SIG1273 gel had ~1.0 Log 10 colony reduction
      over the length of the study, a statistically significantly improvement when
      compared with vehicle. No significant effects above vehicle were observed for
      noninflammatory lesions. CONCLUSIONS: SIG1273 represents a novel cosmetic
      functional ingredient that provides a safe dual modulating benefit to individuals
      with acne prone skin by reducing P. acnes counts and reducing inflammation.

PMID- 23174051
TI  - Global, 3-dimensional approach to natural rejuvenation: part 1 - recommendations
      for volume restoration and the periocular area.
AB  - BACKGROUND: New techniques and products have lead to a global approach for the
      treatment of signs of aging. However, there is little published literature on the
      procedures involved in this approach and currently no validated recommendations
      exist. OBJECTIVES: To provide a detailed, practical guide to midfacial volume
      restoration and rejuvenation of the periocular area based on expert consensus
      recommendations. METHODS: The expert committee took into account both volumetric
      and dynamic aspects of treatment, as well as benefits of treatment combinations,
      for example, combining OnabotulinumtoxinA with hyaluronic acid (HA) fillers and
      volumizers. An aging severity scale was established for each area, together with
      recommendations of appropriate products, doses, site, depth, and injection
      techniques, as well as rules to be respected. RESULTS: The expert group concluded
      that volume restoration of the midface is the first essential step in the global
      approach because treatment for this area has the most significant positive
      impact. Firstly, it is important to restore the malar contour, as malar volume
      anchors the structure of the midface. Secondly, an assessment of the effects of
      malar enhancement on the appearance of the nasolabial folds and the nasojugal
      fold (tear trough) should be conducted because these aging signs may be decreased
      by malar enhancement. Finally, treatment for the nasolabial folds and periorbital
      area with HA should be performed when needed. CONCLUSIONS: Practical guidance is
      provided for midfacial volume restoration and rejuvenation of the periocular area
      based on validated expert consensus recommendations. This will help esthetic
      facial physicians to achieve optimum outcomes.

PMID- 23174053
TI  - Stem cells and the skin.
AB  - Stem cells live long lives, renew themselves, and differentiate into more mature,
      less potent, specialized cells, such as epidermal keratinocytes and dermal
      fibroblasts. Stem cells can be embryonic, if derived from an embryo, or
      adult/somatic if derived from postembryonic tissue. By producing new skin cells,
      stem cell division and differentiation can potentially rejuvenate skin and
      restore hair. To reproduce, stem cells can undergo symmetric nondifferentiative
      or differentiative divisions, or asymmetric differentiative divisions. Asymmetric
      divisions reproduce the stem cell and provide a more differentiated, but less
      potent transient amplifying cell. Divisions and differentiation of transient
      amplifying cells regenerate tissues by producing cells of a specific lineage, for
      example, keratinocytes. Epidermal stem cells lie in niches in the interfollicular
      epidermis, sebaceous gland, and in the bulge regions of hair follicles. These
      epidermal stem cells renew the epidermis, the sebaceous glands, and hair
      follicles after mature cells die. Dermal stem cells lie in the hair papillae,
      around pericytes, and elsewhere among other dermal cells. These form pericytes,
      myoblasts, fibroblasts, chondrocytes, and other specialized dermal cells. Along
      with other signaling pathways, the Wnt signaling pathway controls stem cell fate.
      Wnt signals enlist two functionally and chemically different gene coactivators to
      direct the time and type of replicative divisions. Stem cells may help to heal
      wounds, repair damaged tissues, regenerate aged skin, and reinvigorate growth of
      skin, hair, nails, and mucous membranes.

PMID- 23174052
TI  - Oligosaccharides of hyaluronic acid increased epidermal cell stemness by
      modulation of integrin expression.
AB  - BACKGROUNDS: Hyaluronic acid (HA) is an abundant matrix component and is degraded
      into polymers of various sizes. These generated fragments appear to have
      properties that affect wound healing of the skin. In industry, small-sized HA is
      used as a moisturizing agent but can have biologic effects when it is absorbed
      through the skin with barrier disruption. AIMS: In this study, the regenerative
      effects of these molecules were investigated using skin equivalent (SE) models.
      METHODS: Normal human keratinocytes and fibroblasts were isolated, and the
      effects of oligosaccharides of HA were tested in cultured keratinocytes and in
      the SE model. RESULTS: In the monolayer of cultured keratinocytes,
      oligosaccharides of HA did not affect the proliferation of keratinocytes.
      However, the epidermis became thicker when oligosaccharides of HA were added
      during the culture of SE models. The data also showed that oligosaccharides of HA
      promote the differentiation of the epidermis. Furthermore, the expression of p63,
      integrin-alpha6 and integrin-beta1 was increased. Western blot analysis also
      showed increased expression of both integrins. CONCLUSIONS: These findings
      suggest that oligosaccharides of HA increase the differentiation of the
      epidermis. In addition, increased number of p63, a putative stem cell marker of
      the skin, showed that oligosaccharides of HA promote the survival of basal stem
      cells by modulating the expression of integrin-alpha6 and integrin-beta1.
      Finally, it can be said that inflammation-induced small-sized oligosaccharides
      can have beneficial effects on epidermal regeneration and topically applied
      oligosaccharide of HA can have healing effects in skin problems.

PMID- 23174054
TI  - One-step technique for esthetic earlobe repair.
AB  - Earlobe tear is a common cause for earlobe disfigurement. Different techniques
      described in the literature for earlobe repair usually require re-piercing of the
      ear after some time at a different site avoiding the scar tissue. If re-piercing
      is performed at the original site because of cosmetic reasons, there is risk of
      tract elongation. We describe a new technique in which polypropylene deep buried
      suture is left in situ to strengthen the repaired scar tissue with preservation
      of perforation at the upper end of the slit, thereby giving good cosmetic result
      to the patient in single sitting.

PMID- 23174055
TI  - Stability, transdermal penetration, and cutaneous effects of ascorbic acid and
      its derivatives.
AB  - Topically applied antioxidants exert their benefits by offering protection from
      damaging free radicals and over-the-counter cosmeceuticals incorporating
      antioxidants are among the most popular anti-aging products available. One potent
      antioxidant of particular note, vitamin C, has been extensively utilized because
      it possesses a variety of other cutaneous benefits including photoprotection from
      UV A & B, neocollagenesis, inhibition of melanogenesis and improvement of a
      variety of inflammatory skin disorders. However, the instability of this water
      soluble vitamin, together with difficulties associated with its topical delivery,
      has presented issues for the formulation chemist. This article reviews the
      scientific data and clinical studies that underpin the stability, percutaneous
      absorption, and cutaneous effects of vitamin C together with its commonly
      utilized, commercially available derivatives.

PMID- 23174056
TI  - Dermabrasion may repigment vitiligo through stimulation of melanocyte precursors
      and elimination of hyperkeratosis.
AB  - BACKGROUND: The observation of successful repigmentation of recalcitrant vitiligo
      patches in spite of rejection of epithelial grafts from the dermabraded skin
      presented a query about possible efficiency of dermabrasion itself in the
      repigmentation process. OBJECTIVES: The aim of this work is to investigate the
      possible effectiveness of dermabrasion alone in managing stable vitiligo.
      METHODS: Ten patients with vitiligo were candidates in this study. Superficial
      dermabrasion was carried out using proper diamond fraises. Biopsy was obtained
      after 10 days of the procedure and examined pathologically. The patients were
      followed up for 3 months. RESULTS: Dermabrasion was able to repigment
      vitiliginous patches completely in six patients and partially in two patients,
      while two cases failed to repigment at all. Spindle melanocyte precursors were
      demonstrated in the epidermis 10 days after abrasion with regaining normal
      thickness of keratin layers. CONCLUSION: Dermabrasion can repigment vitiligo
      through stimulation of melanocyte stem cells and elimination of hyperkeratosis.

PMID- 23174057
TI  - The activity of adenosine deaminase and oxidative stress biomarkers in scraping
      samples of acne lesions.
AB  - BACKGROUND: Acne vulgaris is one of the most common dermatological diseases, and
      its pathogenesis is multifactorial. Although there are some reports about role of
      oxidative stress biomarkers in blood, serum, plasma in the pathogenesis of acne,
      there has been no report about oxidative stress biomarkers in scraping samples.
      For this reason, the aim of our study is to determine the role of oxidative
      stress biomarkers and adenosine deaminase (ADA) in scraping samples of acne
      lesion and to determine a possible link with the clinical severity. Fifty
      patients with different severity of acne vulgaris and forty healthy controls were
      enrolled. In both groups, ADA and oxidative stress biomarkers such as the levels
      of malondialdehyde (MDA), and reduced glutathione (GSH), the activities of
      superoxide dismutase (SOD) and catalase (CAT) in scraping samples were measured
      spectrophotometrically. The levels of SOD, CAT, GSH, MDA, and ADA of patients
      with acne were higher than the control patients (P < 0.05). ADA and MDA levels in
      patients with severe acne were significantly higher about two- to four-fold
      compared with other acne groups (P < 0.05). However, CAT, SOD, and GSH levels
      were lower in patients with severe acne vulgaris than the others (P < 0.05).
      Increased antioxidant enzyme levels of scraping samples in patients might be a
      local response of the organism to increased oxidative stress. Also, we believe
      that oxidative stress increases in parallel with the disease severity, hence
      antioxidant therapy may be beneficial if given in addition to the routine
      treatment of severe acne.

PMID- 23174058
TI  - Arthroscopic resection arthroplasty for malunited intra-articular distal radius
      fractures.
AB  - PURPOSE: Cartilage damage of the carpals is a contraindication for corrective
      osteotomy of the malunited intra-articular distal radius fracture and typically
      is treated in the symptomatic patient with a salvage procedure. Here, we present
      our experience and early results with arthroscopic resection arthroplasty of the
      radiocarpal joint. METHODS: We treated 10 patients (age, 17-68 y; average, 53 y)
      who had intra-articular malunion of the distal radius with mirror erosion on the
      carpals. The original fracture occurred 4 to 36 months (average, 9 mo) before our
      intervention. We performed arthroscopic arthrolysis and resected the offending
      portion of the radial malunited fragment, eliminating the stepoff and creating a
      smoother joint surface. Range of motion was started immediately after the
      operation, except in 2 patients. RESULTS: The locations of the malunions were
      evenly distributed between the scaphoid fossa, the lunate fossa, or both.
      Stepoffs varied from 2 to 6 mm. We resected up to 60% of the entire radial
      articular surface to obtain a smooth surface (average, 28%; range, 20% to 60%).
      All patients reported immediate relief of pain and improvement in motion
      (particularly extension). At the latest follow-up (average, 28 mo; range, 13-42
      mo), average extension improved from 24 degrees  to 54 degrees , average grip
      strength improved from 47% to 89% of the contralateral wrist, average
      Disabilities of the Arm, Shoulder, and Hand score improved from 74 to 18, and
      average Patient-Rated Wrist Hand Evaluation score improved from 79 to 15.
      CONCLUSIONS: The aim of the operation was to relieve patients' pain by providing
      a smooth, although fibrocartilaginous, surface for the carpus to glide on the
      radius. The follow-up was short and the results may be short-lived. However, for
      the younger patient, it may provide a temporary alternative to partial wrist
      arthrodesis with minimal morbidity, and for the less demanding patients, it may
      be a definitive procedure.

PMID- 23174059
TI  - Ulnar shortening for adolescent ulnar impaction syndrome: radiological and
      clinical outcomes.
AB  - PURPOSE: To determine the amount of shortening needed in an ulna to achieve final
      neutral ulnar variance in adolescents with ulnar impaction syndrome. Radiological
      and clinical outcomes were evaluated after ulnar shortening and after growth had
      stopped. METHODS: From February 2006 to February 2009, we prospectively followed
      16 consecutive patients treated with a shortening osteotomy for positive ulnar
      variance. The study group included 10 boys and 6 girls with an average age of
      16.1 years. The closed medial half-side of the physis of the distal radius was
      used to measure the variance as a reference for the ulna. Based on the radius
      without any growth potential, the amount of shortening was determined for the
      ulna with potential for further growth. The preoperative, postoperative, and
      final ulnar variances were evaluated. The clinical results were compared before
      surgery and at the time of growth termination. RESULTS: Preoperative ulnar
      variance was 3.4 mm +/- 0.6 mm and the amount to be shortened was 6.1 mm +/- 1
      mm. The final ulnar variance was 0.2 mm +/- 0.3 mm. The mean visual analog scale
      pain score improved from 6.6 +/- 1.0 before surgery to 2.2 +/- 0.5 after surgery.
      The mean range of forearm rotation increased from 132 degrees  +/- 11 degrees 
      before surgery to 170 degrees  +/- 16 degrees  at final follow-up. In addition,
      grip strength was 15.3 kg +/- 7.6 kg (71% of grip strength on the unaffected
      side) before surgery and 19.8 kg +/- 4.9 kg (90% of grip strength on the
      unaffected side) at final follow-up. The modified Mayo Wrist Score was 85 +/- 8
      at the final follow-up. No cases of complications or treatment failure occurred.
      CONCLUSIONS: Ulnar shortening was considered a useful procedure for adolescents
      with ulnar impaction syndrome, particularly if the measurement for the shortening
      amount was determined using the physis of the distal radius and ulna.

PMID- 23174060
TI  - Clinical, radiographic, and arthroscopic outcomes after ulnar shortening
      osteotomy: a long-term follow-up study.
AB  - PURPOSE: Previous studies have investigated the long-term outcomes of ulnar
      shortening osteotomy (USO) in the treatment of ulnocarpal abutment syndrome
      (UCA), but none have used arthroscopic assessments. The purpose of this study was
      to investigate the long-term clinical outcomes of USO with patient-based,
      arthroscopic, and radiographic assessments. METHODS: We retrospectively reviewed
      30 patients with UCA after a minimum follow-up of 5 years, with arthroscopic
      evaluations at the time of both USO and plate removal. We confirmed the initial
      diagnosis of UCA by radiography and arthroscopy. Mean age at the time of index
      surgery was 37 years. Mean duration of follow-up was 11 years (range, 5-19 y). We
      obtained Disabilities of the Arm, Shoulder, and Hand and Hand20 self-assessments
      postoperatively for all patients. Bony spur formation was evaluated
      postoperatively from plain radiographs. RESULTS: We detected triangular
      fibrocartilage complex (TFCC) disc tear in 13 wrists arthroscopically at the time
      of USO. Of these, 10 showed no evidence of TFCC disc tear at second-look
      arthroscopy. The remaining 17 cases showed no TFCC disc tear at either first- or
      second-look arthroscopy. Follow-up radiography revealed that bony spurs at the
      distal radioulnar joint had progressed in 13 wrists. Disabilities of the
      Shoulder, Arm, and Hand and Hand20 scores did not significantly correlate with
      the presence of bony spurs or TFCC disc tears. Range of motion decreased
      significantly with age only. Lower grip strength correlated with bony spur and
      lower radial inclination. Triangular fibrocartilage complex tear, male sex, and
      advanced age were associated with lower Disabilities of the Shoulder, Arm, and
      Hand and Hand20 scores. CONCLUSIONS: Ulnar shortening osteotomy achieved
      excellent long-term results in most cases. Most TFCC disc tears identified at the
      initial surgery had healed by long-term arthroscopic follow-up. We suggest that
      UCA with a TFCC disc tear is a good indication for USO.

PMID- 23174061
TI  - Functional results of the Darrach procedure: a long-term outcome study.
AB  - PURPOSE: To assess long-term functional outcome after ulnar head excision for
      distal radioulnar joint dysfunction with prior or concomitant wrist trauma. We
      hypothesized that long-term outcomes would reflect good functional results with
      satisfactory pain relief. METHODS: A retrospective chart review identified
      patients who had undergone the Darrach procedure for traumatic or posttraumatic
      distal radioulnar joint (DRUJ) pathology. We assessed subjective outcomes using a
      visual analog scale questionnaire to assess pain, wrist stability, and overall
      satisfaction. We evaluated objective functional outcomes using the Quick
      Disabilities of the Shoulder, Arm, and Hand and Patient-Rated Wrist Evaluation
      measures. Final radiographs were compared with preoperative x-rays to investigate
      the effect of possible ulnar impingement syndrome (convergent instability).
      RESULTS: A total of 98 patients with 99 wrists met our predetermined inclusion
      criteria. Of these, 27 patients with a total of 27 wrists were available for
      final follow-up, 15 of whom were available for final in-office follow-up with
      radiographs (6-20 y). Patients displayed an average Quick Disabilities of the
      Shoulder, Arm, and Hand score of 17 and a Patient-Rated Wrist Evaluation score of
      14. Final average visual analog scale scores for pain (0-4), pain with activity
      (0-4), overall satisfaction (0-4), and wrist stability (0-10) were 0.1, 0.6, 3.7,
      and 1.5, respectively. Final average wrist range of motion was 85 degrees /78
      degrees  and 41 degrees /45 degrees  for pronation-supination and flexion
      extension, respectively. A total of 7 patients displayed radioulnar impingement
      based on dynamic radiography. This ulnar impingement was not associated with
      clinical reports of pain and did not affect outcome measures in a statistically
      significant manner. CONCLUSIONS: The Darrach procedure provides reliably good
      long-term subjective and objective results for the treatment of a symptomatic
      DRUJ after a distal radius fracture. Patients can expect to have excellent
      forearm range of motion at long-term follow-up. Nearly one-half of patients had
      dynamic convergence of the DRUJ when stressed radiographically; however, the
      presence of radiographic dynamic convergence did not influence clinical outcomes.

PMID- 23174062
TI  - Biomechanical analysis of a volar variable-angle locking plate: the effect of
      capturing a distal radial styloid fragment.
AB  - PURPOSE: Variable-angle volar locked constructs for distal radius fractures are a
      recent treatment addition. This study sought to biomechanically evaluate a
      variable-angle volar locking plate as compared with a fixed-angle construct.
      METHODS: We created 2 different AO-C3 osteotomies in fourth-generation synthetic
      composite distal radiuses and labeled them proximal and distal. The distal
      osteotomy consisted of a smaller radial styloid fragment. We then fixed both sets
      of specimens with either a fixed-angle or variable-angle volar locking construct.
      We tested samples in axial compression with regard to cyclical loading and load
      to failure. Articular stepoff, stiffness, and load to failure data were then
      analyzed. RESULTS: Neither the proximal nor the distal osteotomy groups showed
      articular failure after cyclic loading, significant loss of stiffness over
      cycling, or superior stiffness compared with the other. After load to failure in
      the proximal osteotomy, 1 of 8 fixed-angle and none of 8 variable-angle
      constructs had articular failure, whereas in the distal osteotomy, all 8 fixed
      angle and none of 8 variable-angle constructs had articular failure. CONCLUSIONS:
      Variable-angle and fixed-angle volar locked fixation of unstable intra-articular
      distal radius fractures in fourth-generation composite radii provide mechanically
      sound constructs with high load to failure values and no loss of stiffness over
      testing. The variable-angle construct exhibited excellent resistance to articular
      stepoff at load to failure and no loss of stiffness throughout cyclic loading,
      and did not exhibit significantly less overall stiffness compared with fixed
      angle constructs. The variable-angle fixation exhibited a distinct mechanical
      advantage over fixed-angle fixation in the setting of a smaller radial styloid
      fragment. CLINICAL RELEVANCE: Variable-angle constructs could be expected to hold
      up to standard loads in the postoperative period as well as traditional fixed
      angle devices. The additional cost associated with variable-angle constructs may
      be warranted when treating distal radius fractures with radial styloid fragments,
      owing to the fragment-specific fixation allowed by customized screw placement.

PMID- 23174063
TI  - Biomechanical comparison of parallel versus 90-90 plating of bicolumn distal
      humerus fractures with intra-articular comminution.
AB  - PURPOSE: To compare the biomechanical properties of 90-90 versus mediolateral
      parallel plating of C-3 bicolumn distal humerus fractures. METHODS: We created
      intra-articular AO/Orthopaedic Trauma Association C-3 bicolumn fractures in 10
      fresh-frozen matched pairs of cadaveric elbows. We determined bone mineral
      density of the metaphyseal region with dual-energy x-ray absorptiometry. The
      matched pairs of elbows were randomly assigned to either 90-90 or parallel plate
      fixation. We tested anteroposterior displacement at a rate of 0.5 mm/s to a
      maximum load of +/- 100 N for both the articular and entire distal humerus
      segments. We tested torsional stability at a displacement rate of 0.1 Hz to a
      maximum torque of +/- 2.5 Nm. After cyclical testing, we loaded the specimens in
      torsion to failure. RESULTS: There was no significant difference in the bone
      density of the paired specimens. Compared with parallel fixation, 90-90 plate
      fixation had significantly greater torque to failure load. Both plating
      constructs were equally sensitive to bone density. Both techniques had the same
      mode of failure in torsion, a spiral fracture extending from the medial plate at
      the metaphyseal-diaphyseal junction. There was no significant difference in the
      stiffness of fixation of the articular fragment or the entire distal segment in
      anteroposterior loading. CONCLUSIONS: This study demonstrated that 90-90 and
      parallel plating had comparable biomechanical properties for fixation of
      comminuted intra-articular distal humerus fractures, and that 90-90 plating had
      greater resistance to torsional loading.

PMID- 23174064
TI  - Effect of lactoferrin peptide (PXL01) on rabbit digit mobility after flexor
      tendon repair.
AB  - PURPOSE: Restoration of digital function after flexor tendon injuries remains a
      clinical challenge. Complications such as adhesion formation and tendon rupture
      can lead to limited hand function. The aim of this study was to compare the
      effects of the lactoferrin-derived peptide, PXL01, formulated in sodium
      hyaluronate (SH), with SH alone on joint mobility as an indirect measure of
      postsurgical adhesion prevention and healing strength of the tendon and to
      elucidate the most optimal concentration of PXL01. METHODS: Using a rabbit flexor
      tendon repair model, in which the deep flexor tendon was fully transected and
      repaired, PXL01 in SH or SH alone was administered between the repaired tendon
      and the tendon sheath before closure of the surgical wound. Three concentrations
      of PXL01 in SH (5, 20, or 40 mg/mL) were compared to determine the lowest
      effective concentration. The repaired tendons were evaluated 7 weeks after
      surgery by measuring the proximal interphalangeal joint mobility by full range of
      flexion assessment and the tendon repair strength. RESULTS: Treatment with PXL01
      formulated in SH resulted in improved mobility of the proximal interphalangeal
      joint with an average of 10 degrees , corresponding to improvement of
      approximately 25% to 60% of the flexion of nonoperated toes at the different
      measuring points compared with SH alone. The difference was statistically
      significant in 5 out of 6 measuring points (0.5, 1, 2, 3, and 4 N; P < .05). The
      dose-response study indicated that the lowest effective concentration of PXL01
      was 20 mg/mL. There was no difference in healing strength of the tendon between
      the groups as assessed by load-to-failure breaking strength. CONCLUSIONS: PXL01
      in SH significantly improved the mobility compared with the carrier SH alone,
      without any negative effect on healing strength, and PXL01 at 20 mg/mL was the
      lowest effective concentration. CLINICAL RELEVANCE: The result provides a
      valuable basis for a clinical trial to assess efficacy and safety of PXL01 in
      clinical hand surgery.

PMID- 23174065
TI  - The effect of core and epitendinous suture modifications on repair of
      intrasynovial flexor tendons in an in vivo canine model.
AB  - PURPOSE: To determine in vivo effects of modifications to core and epitendinous
      suture techniques in a canine intrasynovial flexor tendon repair model using
      clinically relevant rehabilitation. Our null hypothesis was that gap formation
      and rupture rates would remain consistent across repair techniques. METHODS: We
      evaluated gap formation and rupture in 75 adult mongrel dogs that underwent
      repair of intrasynovial flexor tendon lacerations followed by standardized
      postoperative therapy. The current suture technique was a 4-0, 8-strand core
      suture with a purchase of 1.2 cm and a 5-0, epitendinous suture repair with a 2
      mm purchase length and depth. We compared gap and failure by chi-square analysis
      to a historical group of in vivo repairs (n = 76) from the same canine model
      using 8-strand core suture repair with purchase of 0.75 cm and 6-0 epitendinous
      suture with a 1-mm purchase length and depth. RESULTS: A total of 93% of tendons
      (n = 70) demonstrated gapping of less than 3 mm using the current suture
      technique. Five percent of tendons (n = 4) had a gap of 3 mm or greater, and
      there was 1 repair site failure. This was significantly improved over the
      comparison group of historical 8-strand core repair technique, which resulted in
      82% (n = 62) of repairs with a gap of less than 3 mm and 7 failures (9%).
      CONCLUSIONS: In an in vivo model, current modifications to suture techniques for
      intrasynovial flexor tendon repair demonstrated significant improvements in gap
      formation and rupture compared with a similar technique using shorter purchase
      lengths and shallower purchase depth. CLINICAL RELEVANCE: Suggested repair
      modifications for the treatment of zone II flexor tendon transections demonstrate
      improvements in gap formation and tendon rupture in vivo.

PMID- 23174067
TI  - Distraction osteogenesis and free nail graft after distal phalanx amputation.
AB  - PURPOSE: To describe the results in patients treated with distraction
      osteogenesis combined with free nail graft after distal phalanx amputation.
      METHODS: We analyzed 14 patients with distal phalanx amputation (13 women). Mean
      age was 35 years. There were 9 amputations of the index finger, 3 of the middle
      finger, and 1 each of the thumb and ring finger. We started bone distraction 7
      days after surgery, with 1 mm distraction every 3 days. After bone elongation, we
      inserted a free composite nail graft at the dorsal tip of the distracted finger.
      We evaluated distraction length, consolidation time, aesthetic result (using the
      Foucher and Leclere score), and complications. RESULTS: The mean bone elongation
      was 17 mm and mean consolidation time was 149 days. Nail cosmetic results were
      satisfactory; the mean total Foucher score was 14 out of 20. Mean individual
      scores were patient's opinion (7.8 out of 10), adequate length (1.2 out of 2.5),
      adequate alignment (1 out of 1), adequate width (1.8 out of 4), and dorsal scar
      quality (2.2 out of 2.5). The mean total Leclere score was 14 out of 20. All
      patients retained sensibility in the grafted area and none had healing
      abnormalities. The mean opinion about the donor site was 7.5 out of 8. Nail
      growth less than 50% occurred in 2 patients. Mean follow-up was 62 months.
      CONCLUSIONS: Distraction osteogenesis combined with free nail graft is a
      therapeutic option when replantation is not an option or when it fails. However,
      treatment takes time and requires the involvement of the patient, family, and
      medical team.

PMID- 23174066
TI  - Clinical outcomes of zone II flexor tendon repair depending on mechanism of
      injury.
AB  - PURPOSE: To determine whether mechanism of injury affects outcomes of Zone II
      flexor tendon repairs. METHODS: We retrospectively analyzed patients who
      underwent Zone II flexor tendon repair between 2001 and 2010 with a minimum of 12
      month follow-up. Exclusion criteria included fingers with fracture, pulley
      reconstruction, or flexor tendon bowstringing. The saw group injuries were from
      saws or from tearing mechanisms; the sharp group had clean transection injuries
      from knives or glass. At final evaluation, primary outcomes were total passive
      motion (TPM) and total active motion (TAM) at the proximal interphalangeal and
      distal interphalangeal joints. Secondary comparisons included strength,
      Disabilities of the Shoulder, Arm, and Hand (DASH) score, percentage of
      postoperative tendon rupture, and percentage of patients requiring secondary
      surgery. The saw group had 13 patients with 17 fingers studied. The sharp group
      had 21 patients with 24 fingers studied. All patients had primary flexor
      digitorum profundus repairs in Zone II. Operative records review confirmed for
      all but 1 patient that flexor digitorum profundus injuries were repaired with a
      minimum of a 4-strand core suture technique. In the saw group, 9 of 14 fingers
      with a 50% or greater laceration of flexor digitorum superficialis were repaired;
      in the sharp group, 15 of 18 such flexor digitorum superficialis injuries were
      repaired. Average follow-up was 4 years (range, 1-9 y). RESULTS: The saw group
      had significantly less TAM and TPM compared with the sharp group. There was no
      significant difference in DASH scores, strength measurements, or tendon rupture
      rates. The rate of secondary surgery was significantly higher in the saw group.
      CONCLUSIONS: Tearing types of injury, such as those caused by saws, led to poorer
      outcomes for Zone II flexor tendon injuries compared with sharp injuries at an
      average follow-up of 4 years. Our results can be useful when discussing expected
      outcomes. Mechanism of injury in Zone II flexor tendon lacerations may eventually
      help define optimal treatment.

PMID- 23174068
TI  - Intramedullary fixation in digital replantation using bioabsorbable poly-DL
      lactic acid rods.
AB  - PURPOSE: To evaluate bioabsorbable poly-DL-lactic acid (PDLLA) intramedullary
      rods for fracture fixation of amputated digits. METHODS: From October 2005 to
      October 2007, we used bioabsorbable rods made of PDLLA as intramedullary fixation
      in osteosynthesis procedures in 9 cases of digital replantation. Four cases
      involved the middle phalanx and 5 the proximal phalanx. The amputation level was
      diaphyseal in all cases. All patients were followed up from 6 months to 2 years,
      with an average of 13 months. RESULTS: All fractures healed in 6 to 8 weeks.
      There were no infections. There was no evidence of hardware failure at 4 weeks
      after surgery. According to the Tamai et al criteria, the results were excellent
      in 8 cases and good in 1. CONCLUSIONS: Using bioabsorbable PDLLA rods for
      intramedullary fixation can be an effective technique for replantation with
      fractures through the proximal or middle phalanges. Bioabsorbable rods can
      provide rigid stable fixation, which allows early mobilization.

PMID- 23174069
TI  - Successful use of ultrasound-guided compression for a princeps pollicis artery
      pseudoaneurysm: case report.
AB  - A 73-year-old man receiving heparin developed a large hematoma in the first web
      after a routine blood draw. Color Doppler ultrasound demonstrated a
      pseudoaneurysm of the princeps pollicis artery. Ultrasound-guided compression
      resulted in successful thrombosis of the pseudoaneurysm.

PMID- 23174070
TI  - Wrist, first carpometacarpal joint, and thumb interphalangeal joint arthrodesis
      in patients with brachial plexus injuries.
AB  - PURPOSE: Wrist arthrodesis, first carpometacarpal joint arthrodesis, and thumb
      interphalangeal joint arthrodesis can be used in conjunction with other
      reconstructive measures to improve function and grasp in patients with complete
      brachial plexus injuries. This study evaluates wrist arthrodesis, first
      carpometacarpal joint arthrodesis, and thumb interphalangeal joint arthrodesis as
      measured by fusion rate, complications, and clinical outcomes. METHODS: A
      retrospective chart review was performed for 24 skeletally mature patients with
      brachial plexus injuries treated with wrist arthrodesis by a dorsal plating
      technique, first carpometacarpal joint arthrodesis by staples, and thumb
      interphalangeal joint arthrodesis by a tension band wiring technique. Nineteen
      patients were subjectively evaluated using prearthrodesis and postarthrodesis
      Disabilities of the Shoulder, Arm, and Hand scores, visual analog pain scores,
      and a visual analog scale assessing appearance, function, hygiene, ease of daily
      care, pain, and overall satisfaction. RESULTS: There was 100% union rate with 1
      postarthrodesis complication. One patient required wrist fusion plate removal
      because of painful hardware. Subjective patient assessments showed a
      statistically significant (P < .001) improvement in Disabilities of the Shoulder,
      Arm, and Hand scores (from 51 to 28) and pain scores (from 5.3 to 3.2) before and
      after arthrodeses. The visual analog questionnaire results revealed improvements
      in appearance, function, daily cares, hygiene, pain, and satisfaction.
      CONCLUSIONS: Wrist arthrodesis, first carpometacarpal joint arthrodesis, and
      thumb interphalangeal joint arthrodesis had high union rates with minimal
      complications. Patients benefited from the improved function of their upper
      extremities and were satisfied with the surgery. The use of wrist, first
      carpometacarpal joint, and thumb interphalangeal joint arthrodeses in combination
      should be considered one of the reconstructive possibilities for patients with
      complete or nearly complete brachial plexus injuries.

PMID- 23174071
TI  - Pulse oximetry measurements in the evaluation of patients with possible thoracic
      outlet syndrome.
AB  - PURPOSE: We present our experience in using pulse oximetry as an aid in the
      diagnosis of thoracic outlet syndrome (TOS). Our attention was given to those
      symptomatic patients without objective confirmatory data on imaging or
      electrodiagnostic evaluation. METHODS: Using a pulse oximeter, we measured the
      oxygen saturation and the pulse rate during a provocative extremity abduction
      stress test exercise maneuver in 18 patients with symptoms and signs consistent
      with a diagnosis of nonspecific neurogenic TOS. The oxygen saturation and pulse
      rates in 18 asymptomatic subjects were used as a control. RESULTS: Resting oxygen
      saturation above 97% was present in both groups initially. After the provocative
      exercise maneuver, there was a significant reduction in the oxygen saturation
      levels, which dropped to 86% in the symptomatic TOS group compared with 94% in
      the control group. There was a significant increase in pulse rate in those
      subjects suspected of having TOS compared with a minimal increase in pulse rate
      in control subjects. CONCLUSIONS: Pulse oximetry produced objective confirmatory
      measurements, which support a hypothesis that hypoperfusion in the upper limb
      during provocative activities or exercise may cause disabling symptoms associated
      with nonspecific neurogenic TOS. This method may be a useful, noninvasive, rapid,
      and inexpensive clinical tool in the diagnosis of TOS, a condition frequently
      lacking in objective, confirmatory diagnostic data.

PMID- 23174072
TI  - Diagnostic biopsy of the pronator teres and a motor branch of the median nerve:
      indications and technique.
AB  - PURPOSE: Biopsy of muscle tissue and motor nerve is helpful in the neurological
      evaluation of patients who present with upper limb and/or diffuse motor weakness.
      The procedure is indicated to supplement clinical, serological, and imaging
      diagnostic work-up of myopathic and neuropathic disorders. We describe a surgical
      technique and clinical series of biopsy of the pronator teres muscle and a motor
      branch of the median nerve. METHODS: We performed a retrospective review of 20
      patients who underwent biopsy of the pronator teres and a motor branch of the
      median nerve as part of a clinical, serological, and radiographic evaluation for
      weakness of the upper extremity. All of the biopsies were performed by a single
      surgeon. The surgical technique is described. Follow-up visits with both the
      surgeon and the neurologist were reviewed to evaluate preoperative and
      postoperative neurological function to identify any changes in nerve or muscle
      function and any postoperative complications. RESULTS: Biopsied tissue was
      sufficient for pathological diagnosis in all 20 patients. Diagnoses included
      multifocal motor neuropathy in 14 patients, amyotrophic lateral sclerosis in 3
      patients (2 sporadic; 1 familial), inclusion body myositis (1 patient),
      inflammatory myopathy (1 patient), and chronic inflammatory demyelinating
      polyneuropathy (1 patient). At a mean follow-up of 11 weeks (range, 5-31 wk),
      there were 6 minor surgical complications, all of which were superficial
      hematomas that resolved with use of a compressive wrap. CONCLUSIONS: Biopsy of
      the pronator teres and a motor branch of the median nerve was safe and effective.
      The technique is particularly useful when considering the diagnosis of multifocal
      motor neuropathy affecting the upper extremity.

PMID- 23174073
TI  - Developing the art of scientific presentation.
AB  - PURPOSE: Few guidelines exist regarding the most effective approach to scientific
      oral presentations. Our purpose is to (1) develop a standardized instrument to
      evaluate scientific presentations based on a comprehensive review of the
      available literature regarding the components and organization of scientific
      presentations and (2) describe the optimal characteristics of scientific
      presentations. METHODS: At the Sixty-sixth (2011) Annual Meeting of the American
      Society for Surgery of the Hand, 69 presentations were evaluated by at least 2
      independent observers. A rating instrument was developed a priori to examine
      presentation content (background, methods, results, and conclusions),
      presentation style (speech, structure, delivery, slide aesthetics), and overall
      quality. We examined correlations between reviewers' ratings of each component as
      well as overall perceived quality of the presentation using regression analysis.
      Intraclass correlation coefficients were calculated to measure the degree of
      variation because of reviewer disagreement and identify the aspects of
      presentations that contribute to overall quality. RESULTS: Reviewer agreement was
      high for presentation content, and less than 1% of variation was caused by
      reviewer disagreement for background, methods, and conclusions. With respect to
      presentation style, reviewers agreed most frequently regarding speech and slide
      appearance, and only 9% and 13%, respectively, of the variation was caused by
      reviewer disagreement. Disagreement was higher for delivery and presentation
      structure, and 21% of the variation was attributable to reviewer disagreement.
      Speaker delivery and slide appearance were the most important predictors of
      presentation quality, followed by the quality of the presentation of conclusions
      and background information. Presentation of methods and results were not
      associated with overall presentation quality. CONCLUSIONS: Distinct aspects of
      presentation content and style correlate with quality, which can be reliably and
      objectively measured. By focusing on selected concepts with visually simple
      slides, speakers can enhance their delivery and may potentially improve the
      audience's comprehension of the study findings.

PMID- 23174074
TI  - The use of a tablet computer to complete the DASH questionnaire.
AB  - PURPOSE: To determine whether electronic self-administration of the Disabilities
      of the Arm, Shoulder, and Hand (DASH) questionnaire using a tablet computer
      increased completion rate compared with paper self-administration. METHODS: We
      gave the DASH in self-administered paper form to 222 new patients in a single
      hand surgeon's practice. After a washout period of 5 weeks, we gave the DASH in
      self-administered tablet computer form to 264 new patients. A maximum of 3
      questions could be omitted before the questionnaire was considered unscorable. We
      reviewed the submitted surveys to determine the number of scorable questionnaires
      and the number of omitted questions in each survey. We completed univariate
      analysis and regression modeling to determine the influence of survey
      administration type on respondent error while controlling for patient age and
      sex. RESULTS: Of the 486 total surveys, 60 (12%) were not scorable. A
      significantly higher proportion of the paper surveys (24%) were unscorable
      compared with electronic surveys (2%), with significantly more questions omitted
      in each paper survey (2.6 +/- 4.4 questions) than in each electronic survey (0.1
      +/- 0.8 questions). Logistic regression analysis revealed survey administration
      mode to be significantly associated with DASH scorability while controlling for
      age and sex, with electronic survey administration being 14 times more likely
      than paper administration to yield a scorable DASH. CONCLUSIONS: In our
      retrospective series, electronic self-administration of the DASH decreased the
      number of omitted questions and yielded a higher number of scorable
      questionnaires. Prospective, randomized evaluation is needed to better delineate
      the effect of survey administration on respondent error. CLINICAL RELEVANCE:
      Administration of the DASH with a tablet computer may be beneficial for both
      clinical and research endeavors to increase completion rate and to gain other
      benefits from electronic data capture.

PMID- 23174075
TI  - Diagnosis and management of the acute felon: evidence-based review.

PMID- 23174076
TI  - Posterior interosseous artery distal radius graft for ulnar nonunion treatment.
AB  - The aim of our study was to describe a dorsal distal radius vascularized bone
      graft pedicled on the posterior interosseous artery (PIA), and its clinical
      application in 2 cases of ulnar nonunion. We studied the surgical technique in 5
      freshly injected cadavers. The 4th extensor compartment artery originates from
      the anastomotic arch between the posterior division of the anterior interosseous
      artery and the PIA and provides periosteal branches to supply the dorsal distal
      radius metaphysis. A 2-cm vascularized bone graft can be harvested from the
      radius, and dissection of the PIA enables a long pedicle with a wide arc of
      rotation able to reach the ulnar diaphysis. The approach is limited to the
      forearm and distal radius and has minimal donor morbidity.

PMID- 23174077
TI  - Antipronation spiral tenodesis--a surgical technique for the treatment of
      perilunate instability.
AB  - Perilunate dislocations involve avulsion or rupture of both intrinsic and
      extrinsic ligaments around the lunate. If inadequately treated, these ligaments
      may not heal properly, inducing a particular type of carpal instability
      characterized by the loss of the ability of the carpus to resist pronation
      torques. Six ligaments protect the carpus against excessive intracarpal
      pronation: long radiolunate, palmar and dorsal lunotriquetral, dorsal
      scapholunate, dorsal intercarpal, and palmar scaphocapitate ligaments.
      Collectively, these antipronation ligaments have a spiral configuration around
      the carpus. This article describes a technique to reconstruct this spiral
      arrangement of ligaments using a strip of flexor carpi radialis. To illustrate
      the technique, we describe 1 clinical case with a follow-up of 34 months. The so
      called antipronation spiral tenodesis is only indicated if the instability is
      easily reducible, without cartilage damage.

PMID- 23174078
TI  - Radial head fractures.
AB  - Fractures of the radial head are the most common fractures in the elbow, and they
      frequently have associated ligamentous, cartilaginous, or other bony injuries.
      Clinical assessment and radiological investigation allow for accurate diagnosis
      and the formulation of a management plan. Undisplaced or minimally displaced
      fractures with no rotational block to motion can be treated nonoperatively with
      excellent results expected. The minimum amount of displacement in a partial
      articular radial head fracture required for open reduction and internal fixation
      to provide a superior outcome to nonoperative management is still unknown. Medium
      term data suggest that patients with comminuted radial head fractures do well
      with radial head replacement.

PMID- 23174079
TI  - Guidelines for ethical and professional use of social media in a hand surgery
      practice.
AB  - In growing numbers, patients are using social media platforms as resources to
      obtain health information and report their experiences in the health care
      setting. More physicians are making use of these platforms as a means to reach
      prospective and existing patients, to share information with each other, and to
      educate the public. In this ever-expanding online dialogue, questions have arisen
      regarding appropriate conduct of the physician during these interactions. The
      purpose of this article is to review the laws that govern online communication as
      they pertain to physician presence in this forum and to discuss appropriate
      ethical and professional behavior in this setting.

PMID- 23174080
TI  - An atypical injury distal to the palmar arch.

PMID- 23174081
TI  - What pulley? A letter to the editor.

PMID- 23174082
TI  - Screw prominence of locking plating in distal radius fractures.

PMID- 23174084
TI  - Structural analysis of toad oviductal mucosa in relation to jelly components
      secretion throughout the reproductive cycle.
AB  - In amphibians, the components of the jelly coats that surround the oocytes at the
      time of fertilization and coordinate gamete interaction are secreted by the
      oviduct. We analysed the histological variations in the mucosa of the oviductal
      pars convoluta (PC) of Rhinella arenarum during the reproductive cycle and its
      relationship with secretion. During the preovulatory period, the mucosa reaches a
      high degree of morphological and functional development, with a large number of
      epithelial (ESC) and glandular secretory cells (GSC) loaded with contents that
      are secreted into the oviductal lumen. During the ovulatory period, the secretory
      cells (SC) of both layers present maximum secretory activity through apocrinia
      and merocrinia. While the ESC located at the tips of the folds release their
      content directly in contact with the oocytes, the GSC secrete material from the
      bottom of the epithelial folds that, by interaction with the secretion of the ESC
      in the lateral faces, form a product with a certain degree of organization.
      Secretion is a continuous process with formation of coats of increasing
      complexity from the intermediate proximal zone (IPZ) to the pars convoluta (pc)
      itself, and the passage of the oocyte is a requisite for the organization of the
      jelly coats around the gamete. During the early postovulatory period, although
      there is a marked decrease in the number and volume of the SC, the ESC still
      release material into the oviductal lumen. In the late postovulatory period the
      morphological characteristics of the PC begin to recovery although there is no
      evidence of secretion.

PMID- 23174085
TI  - Chinese patients with spinocerebellar ataxia type 3 presenting with rare clinical
      symptoms.
AB  - Clinical heterogeneity is the prominent feature of spinocerebellar ataxia type 3
      (SCA3) which is sometimes neglected and often impedes the timely diagnosis of
      patients. In this study, the clinical data of 201 unrelated Chinese SCA3 patients
      were retrospectively studied. The rare clinical features were summarized and the
      underlying genetic mutations were screened by direct DNA sequencing. Three
      patients were found primarily presenting with the rare clinical features,
      including dystonic phenotype without response to levodopa, chorea and memory
      decline, and hearing impairment, respectively. We firstly reported three diverse
      heterogeneities of SCA3 patients, which are quite uncommon in the Chinese SCA3
      patients. Our results expanded the variable phenotypes of SCA3 and provided the
      explicit information for the rare and special SCA3 manifestations. Based on this
      new knowledge, we suggested that when the presentation was consistent with HD or
      DRD while negative in the corresponding genetic testing, SCA3 should be
      considered, and clinicians should divert partial attention to the examinations on
      the auditory system of SCA3 patients.

PMID- 23174086
TI  - Preliminary evaluation of the toxic effects of the antifouling biocide Sea-Nine
      211TM in the soft coral Sarcophyton cf. glaucum (Octocorallia, Alcyonacea) based
      on PAM fluorometry and biomarkers.
AB  - Sea-Nine 211TM is a new biocide specifically formulated for antifouling paints
      and being considered to have a low environmental impact. Even with a short
      environmental half-life, this compound can cause toxic effects on marine
      organisms. This study used PAM fluorometry and biomarkers of oxidative stress
      (GST, CAT and LPO) to monitor potential toxic effects of Sea-Nine 211TM on
      fragments of the soft coral Sarcophyton cf. glaucum. After exposure to
      concentrations of 1-100 MUg l(-1) for 72 h, CAT activity was inhibited under the
      two highest concentrations, being in accordance with the activity of GST. LPO
      activity (as TBARS) and photosynthetic efficiency of endosymbiotic zooxanthellae
      were not significantly affected. These results show that PAM fluorometry alone
      cannot detect the full effects of Sea-Nine 211TM on Sarcophyton cf. glaucum and
      should be used together with other biomarkers. This holobiont driven approach to
      evaluate chemical toxicity in photosynthetic corals is therefore recommended for
      biocides which are not photosystem II inhibitors.

PMID- 23174087
TI  - Radiotracer estimates of benthic activity effects on trace metal diffusion into
      mangrove sediments.
AB  - Potential influences of the whole benthic organisms' activity (i.e., coupled
      faunal and microbial effects) on (58)Co, (51)Cr and (65)Zn diffusion into surface
      mangrove sediment layers (0-6 cm depth) were evaluated in 36 h experiments.
      Benthic activity indices (BAI) were proposed, calculated as the relative percent
      difference between untreated sediments and formaldehyde-treated sediments data in
      relation to untreated sediments data. Benthic activity was estimated as
      responsible for 32%-44% of total inventories within sediments, being the chromate
      anion spiked the less affected radiotracer, while (65)Zn was the most sensitive.
      Benthic activity was quantitatively evidenced as a control on trace metal
      diffusion into the sediments, contributing to determine the sediment role as a
      metal sink. This influence can also affect metal potential bioavailability,
      considering that recently diffused metals can be more readily available to
      biological uptake.

PMID- 23174088
TI  - Body mass index (BMI) and breast cancer: impact on tumor histopathologic
      features, cancer subtypes and recurrence rate in pre and postmenopausal women.
AB  - The study aims to analyze the association between body mass index (BMI) at time
      of diagnosis, breast cancer histopathologic features (tumor size, nuclear grade,
      estrogen and progesterone receptor (ER and PgR) and HER-2/neu expression,
      histological subtypes, Ki-67 index, lymphatic/vascular invasion, axillary nodes
      involvement) and incidence of different subtypes defined using hormone receptors
      and HER2/neu expression, according to menopausal status; to evaluate the impact
      of BMI on disease free survival (DFS) at multivariate analysis. A total of 2148
      patients (592 premenopausal, 1556 postmenopausal) were classified into subgroups
      according to BMI distribution. High BMI was significantly associated with larger
      size tumor both in pre (p = 0.01) and postmenopausal women (p = 0.00). Obese
      premenopausal women showed worse histopathologic features (more metastatic
      axillary lymphnodes, p = 0.017 and presence of vascular invasion, p = 0.006)
      compared to under/normal weight group. Postmenopausal patients with BMI > 25
      developed more frequently ER/PgR positive cancers (87% versus 75%, p 0.017),
      while no association was found in premenopausal women. We could not found any
      statistically significant correlation between breast cancer subtypes (luminal A,
      B, HER-2 and basal-like) and BMI both in pre and postmenopause. Higher BMI was
      significantly associated with a shorter DR-FS in postmenopausal women but the
      independent prognostic role of obesity was not confirmed in our analysis.

PMID- 23174089
TI  - [A nasal septal abscess].

PMID- 23174090
TI  - A randomized add-on trial of high-dose D-cycloserine for treatment-resistant
      depression.
AB  - Antagonism of N-methyl-D-aspartate glutamatergic receptors (NMDAR) may represent
      an effective antidepressant mechanism. D-cycloserine (DCS) is a partial agonist
      at the NMDAR-associated glycine modulatory site that at high doses acts as a
      functional NMDAR antagonist. Twenty-six treatment-resistant major depressive
      disorder patients participated in a double blind, placebo-controlled, 6-wk
      parallel group trial with a gradually titrated high dose (1000 mg/d) of DCS added
      to their antidepressant medication. DCS treatment was well tolerated, had no
      psychotomimetic effects and led to improvement in depression symptoms as measured
      by Hamilton Depression Rating Scale (HAMD; p = 0.005) and Beck Depression
      Inventory (p = 0.046). Of the 13 subjects treated with DCS, 54% had a >= 50% HAMD
      score reduction vs. 15% of the 13 patients randomized to placebo (p = 0.039). A
      significant (p = 0.043) treatment* pre-treatment glycine serum levels interaction
      was registered. These findings indicate that NMDAR glycine site antagonism may be
      a cost-effective target for development of mechanistically novel antidepressants.
      Larger-sized DCS trials are warranted.

PMID- 23174091
TI  - Endothelial ultrastructural alterations of intramuscular capillaries in infantile
      mitochondrial cytopathies: "mitochondrial angiopathy".
AB  - Electron microscopy (EM) is a reliable method for diagnosing mitochondrial
      diseases in striated muscle biopsy in infancy. Ultrastructural alterations in
      mitochondria of myofibers are well documented, but there are few studies of
      endothelial involvement in intramuscular capillaries. Quadriceps femoris biopsies
      of five representative infants and toddlers, ages neonate to 3.5 years, were
      performed because of clinical and laboratory data consistent with mitochondrial
      disease without mitochondrial DNA (mtDNA) mutations and likely with nuclear DNA
      mutations. Pathological studies included histochemistry, EM, respiratory chain
      enzymatic assay and mtDNA sequencing and deletion/duplication analysis. EM
      demonstrated frequent and severe alterations of mitochondria in capillary
      endothelium. The most constant changes included: either too few or fragmented
      cristae; stacked and whorled cristae; paracrystallin structures that often were
      large and spheroid with stress fractures; closely apposed membranes of granular
      endoplasmic reticulum surrounding mitochondria with loss of the normal
      intervening layer of cytoplasm; long narrow, thin looped microvilli extending
      into the lumen; and thick microvilli containing large, abnormal mitochondria. We
      conclude that mitochondrial cytopathies in early life exhibit more severe
      ultrastructural alterations in the endothelium than in myofibers and that
      paracrystallin body structure differs, perhaps due to less rigid surrounding
      structures. This distribution may explain the frequent lack of prominent
      histochemical and biochemical abnormalities in muscle biopsies of young patients.
      Endothelial changes do not distinguish the genetic defects. Vascular involvement
      in brain contributes to cerebral lesions and neuronal death by impairment of
      molecular and nutrient transport and ischemia; endothelium in muscle may reflect
      similar changes.

PMID- 23174092
TI  - The effect of spatial smoothing on fMRI decoding of columnar-level organization
      with linear support vector machine.
AB  - We examined how spatial smoothing affects the result of multivariate
      classification analysis using the linear support vector machine (SVM) for
      decoding columnar-level organization. It has been suggested that the effect of
      spatial smoothing on decoding performance is minor because smoothing operation is
      an invertible data transformation and such invertible transformation does not
      remove information in multivariate pattern. Our theoretical consideration,
      however, revealed that generalization score (performance for test samples unused
      during classifier training) was susceptible to non-uniform scaling of input data;
      SVM classifier became less sensitive to variability in shrunk dimension. This
      result indicates that spatial smoothing reduces sensitivity of SVM classifier to
      high spatial frequency pattern so that the effect of smoothing implies the amount
      of information distributed in spatial frequencies. We also examined the effect of
      smoothing in an fMRI experiment of decoding ocular dominance responses. The
      results of group statistic showed that large smoothing reduced decoding
      accuracies while the smoothing effect at individual subject were not the same for
      all subjects. These results suggest that spatial smoothing can have major effect
      on decoding performance and the informative pattern for columnar level decoding
      resides in higher frequencies on average across subjects while it may distribute
      multiple frequencies at individual subject level.

PMID- 23174093
TI  - A method for hypothermia-induction and maintenance allows precise body and brain
      temperature control in mice.
AB  - The benefits as well as mechanisms of hypothermia in brain injuries are actively
      studied at the bench and in the clinic. However, methods used in controlling
      hypothermia vary among laboratories, and usually brain temperatures are not
      monitored directly in animals due to the need for an invasive procedure. Here we
      show a method, water immersion technique, which we developed recently to regulate
      body temperature in mice during hypothermia process. This method significantly
      reduced the temperature variation around target temperature. Importantly, this
      method demonstrated a parallel and consistent relationship between rectal
      temperature and brain temperature (the brain temperature was consistently 0.5C
      higher than rectal temperature) throughout hypothermia maintenance. This
      technique may be well adapted to hypothermia studies in mice and other rodents,
      especially to the assessment and regulation of brain temperature during studies.

PMID- 23174094
TI  - Standardized database development for EEG epileptiform transient detection:
      EEGnet scoring system and machine learning analysis.
AB  - The routine scalp electroencephalogram (rsEEG) is the most common clinical
      neurophysiology procedure. The most important role of rsEEG is to detect evidence
      of epilepsy, in the form of epileptiform transients (ETs), also known as spike or
      sharp wave discharges. Due to the wide variety of morphologies of ETs and their
      similarity to artifacts and waves that are part of the normal background
      activity, the task of ET detection is difficult and mistakes are frequently made.
      The development of reliable computerized detection of ETs in the EEG could assist
      physicians in interpreting rsEEGs. We report progress in developing a
      standardized database for testing and training ET detection algorithms. We
      describe a new version of our EEGnet software system for collecting expert
      opinion on EEG datasets, a completely web-browser based system. We report results
      of EEG scoring from a group of 11 board-certified academic clinical
      neurophysiologists who annotated 30-s excepts from rsEEG recordings from 100
      different patients. The scorers had moderate inter-scorer reliability and low to
      moderate intra-scorer reliability. In order to measure the optimal size of this
      standardized rsEEG database, we used machine learning models to classify
      paroxysmal EEG activity in our database into ET and non-ET classes. Based on our
      results, it appears that our database will need to be larger than its current
      size. Also, our non-parametric classifier, an artificial neural network,
      performed better than our parametric Bayesian classifier. Of our feature sets,
      the wavelet feature set proved most useful for classification.

PMID- 23174095
TI  - A systematic evaluation of whole genome amplification of bisulfite-modified DNA.
AB  - BACKGROUND: Studying DNA methylation profiles in detail should be the first step
      in epigenetic research. Although sodium bisulfite modification of genomic DNA is
      the gold standard method for DNA methylation analysis, this method results in the
      loss of the majority of the DNA material. Whole genome amplification (WGA) of
      bisulfite-modified DNA is expected to provide a rich source of materials, but its
      validity has not been thoroughly evaluated. In this study, we evaluated the
      extent of biased amplification in the WGA of bisulfite-modified DNA and the
      reproducibility of independent WGA reactions. We performed the multiple
      displacement amplification-based WGA separately three times. Each experiment
      included two reactions using 10 or 50 ng of bisulfite-modified DNA as template.
      DNA methylation levels were compared between WGA products and original bisulfite
      modified DNA at about 450,000 CpG sites. RESULTS: Using a sufficient amount of
      bisulfite-modified DNA for WGA was critical for downstream application. The
      considerable deviations from original bisulfite-modified DNA were found in the
      middle range of DNA methylation levels. Distribution of hyper- and
      hypomethylation were equal, which suggested that the deviation at each CpG site
      occurred randomly. Averaging the data from independently amplified WGA products
      dramatically improved the overall quality. CONCLUSIONS: WGA of bisulfite-modified
      DNA could be a valuable tool for epigenetic research, but careful experimental
      design and data interpretation are required.

PMID- 23174096
TI  - Voriconazole in clinical practice.
AB  - Invasive fungal diseases are associated with significant morbidity and mortality
      in immunocompromized patients. Voriconazole is the first line treatment of
      invasive aspergillosis, and has been successfully used in other invasive fungal
      infections, such as candidiasis, fusariosis or  scedosporidiosis. Voriconazole
      has non-linear pharmacokinetics and undergoes extensive hepatic metabolism by the
      cytochrome P450 system that depends on age, genetic factors, and interactions
      with other drugs. Thus, significant interpatient variability is observed after
      administration of the  same dose. Additionally, the therapeutic window is narrow,
      with high risk of side effects at serum levels 3-5 times higher than the minimal
      threshold for efficacy. Therefore, the knowledge of pharmacological properties,
      metabolism, interactions, dosage indications in various populations  and side
      effects is crucial. Therapeutic drug monitoring can help maximize the efficacy
      and minimize the risk of toxicity. Pharmacological, mycological and clinical
      aspects of the treatment with voriconazole are summarized in order to optimize
      its use in daily clinical practice.

PMID- 23174097
TI  - ZAAPS Program results for 2010: an activity and spectrum analysis of linezolid
      using clinical isolates from 75 medical centres in 24 countries.
AB  - The Zyvox(r) Annual Appraisal of Potency and Spectrum (ZAAPS) Program monitors
      the in vitro activities of linezolid and comparator agents for Gram-positive
      organisms in Latin America, Europe, Canada, and the Asia-Pacific. For the 2010
      Program a total of 6305 Gram-positive strains were collected from 75 medical
      centres on five continents (24 countries). Reference broth microdilution
      susceptibility tests were performed on organisms from the following groups:
      Staphylococcus aureus (2875), coagulase negative staphylococci (CoNS) (855),
      enterococci (787), Streptococcus pneumoniae (926), viridans group and other
      streptococci (325), and beta-haemolytic streptococci (507). Linezolid
      demonstrated a 99.81% susceptibility rate among 6305 strains tested from 24
      nations. Of the resistant isolates, four linezolid-resistant strains of
      enterococci (two each for Enterococcus faecalis and Enterococcus faecium) were
      found in four nations (China, Thailand, Germany, and Brazil). Eight CoNS
      (Staphylococcus epidermidis, Staphylococcus hominis) isolates were observed to be
      resistant to linezolid (MIC, >=8 MUg/ml). Two strains from Mexico were determined
      to be from an ongoing epidemic, and investigations showed that isolates from
      Italy and Brazil were also from circulating resistant clones discovered in
      earlier years. MRSA rates varied by region and between nations, as did
      resistances to other potential therapeutic agent options frequently listed for
      MRSA therapy such as clindamycin, fluoroquinolones and
      trimethoprim/sulfamethoxazole. In summary, the 2010 ZAAPS Program demonstrated
      that linezolid activity remains stable around the world with >99% susceptibility.

PMID- 23174098
TI  - Clinical experience with ertapenem in the treatment of infections of the biliary
      tract in daily practice in five Spanish hospitals.
AB  - Efficacy of ertapenem in biliary tract infections in daily practice was
      retrospectively analyzed. Records of patients admitted to five Spanish hospitals
      (January 2007/February 2011) with biliary infections (cholecystitis/cholangitis)
      treated with ertapenem for >=72 hours were reviewed. A total of 187 patients
      (mean 63.8+/-19.3 years, 52.9% males) were identified. Up to 96 (51.3%) were
      operated, with cholecystectomy (97.9%) and primary laparoscopy approach (75%) as
      most frequent intervention. Non-operated patients presented higher age (71.0+/
      17.5 vs 56.9+/-18.5 years; P<0.001), heart insufficiency (11.0 vs 3.1%; P =
      0.044) and the Mortality in Emergency Department Sepsis score (2.99+/-2.26 vs
      1.94+/-2.34; P<0.001); and longer length of stay (10.3+/-6.6 vs 9.1+/-7.0; P =
      0.005). Mean duration of treatment was 6.89+/-3.38 days. Overall favourable
      response was 87.7% (95% CI = 83.0-92.4) at the end of treatment. In the
      multivariate analysis (P<0.001, R2 Cox = 0.10), non-favourable response was
      associated with Charlson index>=5 (OR = 18.71; 95% CI: 1.26-278.55; P = 0.034),
      pericholecystic abscess (OR = 5.30; 95% CI: 1.26-22.37; P = 0.023) and >3 days
      from symptoms start to admission (OR = 3.02; 95% CI: 1.13-8.04; P = 0.027).

PMID- 23174099
TI  - Healthcare expenditures and increasing antimicrobial consumption in Turkey.
AB  - OBJECTIVES: The aim of this study was to assess the trend in antimicrobial
      consumption in Turkey between 2007 and 2010. METHODS: Antimicrobial consumption
      data were obtained from Intercontinental Medical Statistics Turkey office. The
      total antimicrobial consumption data were calculated as Defined Daily Dose
      (DDD)/1000 inhabitant-days. The correlation between the previous five-year period
      and association with the main indicators of economy and healthcare services of
      the country were assessed. RESULTS: Total utilization of antibiotics increased
      from 33.7 to 38.8 DDD/1000 inhabitant-days between 2007 and 2010. A steady
      increase took place during the study period. When this period was compared with
      the previous period (between 2001 and 2006), a similar trend was found. Turkey's
      total healthcare expenditure 2001 to 2010 increased from 4.5 billion Turkish
      Liras to 32 billion Turkish Liras. CONCLUSION: In Turkey, antibiotic consumption
      increased steadily in recent years, with a close relation to government
      healthcare support policy, rising health expenditures and other economical
      indicators.

PMID- 23174100
TI  - Clusterin confers resistance to TNF-alpha-induced apoptosis in breast cancer
      cells through NF-kappaB activation and Bcl-2 overexpression.
AB  - Secretory clusterin (sClu) is an anti-apoptotic protein that plays a role in
      protecting cells from Tumour-necrosis factor (TNF)-alpha-induced apoptosis. The
      aim of the present study was to investigate the molecular mechanisms underlying
      the effect of sClu on TNF-alpha-induced apoptosis  in breast cancer cells. The
      wild-type p53 expressing MCF-7 cell line was engineered to overexpress sClu (MCF
      7/sClu), whereas the MDA-MB-231 cell line with mutant p53 was transfected with a
      sClu silencing siRNA (MDA-MB-231/sClu siRNA). The effects of clusterin
      overexpression and downregulation  on apoptosis and sensitivity to TNF-alpha were
      examined in vitro. Our results showed that TNF-alpha treatment increased Bcl-2
      mRNA and protein levels in breast cancer cells, suggesting that Bcl-2 is directly
      regulated by nuclear factor-kappaB (NF-kappaB) in response to TNF-alpha. The 
      induction of Bcl-2 was mediated by the p65 subunit of NF-kappaB. siRNA-mediated
      silencing of Bcl-2 led to a significant increase in TNF-alpha-induced apoptosis.
      Silencing of sClu in MDA-MB-231/sClu siRNA cells abrogated TNF-alpha-mediated NF
      kappaB activation and Bcl-2 overexpression, and  rendered the MDA-MB-231/sClu
      siRNA cells significantly more sensitive to TNF-alpha-mediated apoptosis than the
      parental cells. Furthermore, overexpression of sClu in MCF-7/sClu cells promoted
      TNF-alpha-mediated NF-kappaB activity and Bcl-2 overexpression, and rendered the
      MCF-7/Clu cells significantly  more resistant to TNF-alpha-mediated apoptosis.
      Inhibition of NF-kappaB activity or p65 and Bcl-2 expression reversed these
      effects. The present results suggested that sClu confers breast cancer cells
      resistance to TNF-alpha-induced apoptosis through NF-kappaB activation and Bcl-2
      overexpression.

PMID- 23174101
TI  - Focused ultrasound-induced blood-brain barrier disruption enhances the delivery
      of cytarabine to the rat brain.
AB  - To investigate the feasibility of using focused ultrasound (FUS) with
      microbubbles for targeted delivery of cytarabine to the brain. Sprague-Dawly rats
      (weighing 200-250 g) received focused ultrasound with intravenous injection
      microbubbles. At 0, 2, 4, 8, and 24 hours (n=5 for each time point) after
      sonication, animals received intravenous administration of cytarabine at a normal
      dose of 4 mg/kg body weight. Additional five rats were given with a high dose (50
      mg/kg body weight) of cytarabine alone. Blood-brain barrier (BBB) permeability
      and cerebral cytarabine were determined. FUS in conjunction with microbubbles
      caused a transient BBB opening. Sonication exposure promoted cytarabine
      accumulation at the sonicated site. Animals injected with a normal dose of
      cytarabine 2 hours after sonication had similar concentrations of cerebral
      cytarabine compared to those with higher cytarabine without sonication. FUS can
      temporarily open the BBB and thus facilitate the penetration of systemic
      cytarabine into the brain.

PMID- 23174102
TI  - Low-dose docetaxel and cisplatin combination chemotherapy for stage II/III
      gastric cancer showing resistance to S-1 adjuvant chemotherapy: a phase I study.
AB  - To establish a safe, long-term regimen of docetaxel (DOC) and cisplatin (CDDP) in
      an outpatient setting for gastric cancer refractory to S-1 adjuvant chemotherapy,
      a dose-escalating phase I study was conducted. Cohorts of patients were treated
      with escalating doses of DOC (starting at 20 mg/m2 per week with 5 mg/m2
      increments) and a fixed dose of CDDP (25 mg/m2). Drugs were administered on days
      1, 8, and 15. A cycle of this treatment was 28 days. In total, 52 courses were
      performed, and the mean number of courses was 5.3. Two of the four patients at
      dose level 3 showed dose-limiting toxicities (grade 4 neutropenia, and grade 3
      anorexia and dehydration). The recommended dose (RD) of DOC was therefore defined
      as 25 mg/m2. There is a need for a phase II clinical trial using this regimen in
      patients with S-1-refractory stage II/III gastric cancer.

PMID- 23174103
TI  - Acute hepatitis B in a patient with OLT during treatment with peg-interferon and
      ribavirin for hepatitis C recurrence.
AB  - The course and outcome of acute viral hepatitis in liver transplanted patients
      with hepatitis C recurrence are unknown. Here we describe a patient who presented
      with acute hepatitis B infection while on treatment with peg-interferon and
      ribavirin for hepatitis C recurrence after liver  transplantation. A nucleoside
      analogue was added (entecavir) and the patient cleared hepatitis C virus (HCV)
      infection and seroconverted to anti-HBs. In this case, the acute hepatitis B
      virus (HBV) infection might have contributed to the clearance of HCV, the
      concomitant immunosuppression  might have lead to the slow clearance of HBV
      infection, and the combined antiviral therapy has helped in the resolution of
      both infections. Hepatitis B vaccination should be recommended in susceptible
      patients waiting for liver transplantation.

PMID- 23174104
TI  - A nematode immunomodulator suppresses grass pollen-specific allergic responses by
      controlling excessive Th2 inflammation.
AB  - Helminth parasites modulate the immune system by complex mechanisms to ensure
      persistence in the host. Released immunomodulatory parasite components lead to a
      beneficial environment for the parasite by targeting different host cells and in
      parallel to a modulation of unrelated inflammatory responses in the host, such as
      allergy. The aim of this study was to investigate the effect of the potent
      helminth immunomodulator, filarial cystatin, in a murine model of airway
      inflammation and hyperreactivity induced by a clinically relevant aeroallergen
      (timothy grass (Phleum pratense) pollen) and on the function of peripheral blood
      mononuclear cells (PBMCs) from timothy grass pollen allergic patients. BALB/c
      mice were systemically sensitised with a recombinant major allergen of timothy
      grass pollen (rPhl p 5b) and then challenged with timothy grass pollen extract
      (GPE) via the airways. Filarial cystatin was applied i.p. during the
      sensitisation phase. Airway hyperresponsiveness to methacholine challenges,
      inflammation of airways, inflammatory cell recruitment, cytokine production and
      lung histopathology were investigated. In a translational approach, PBMCs from
      allergic subjects and healthy controls were treated in vitro with cystatin prior
      to stimulation with GPE. Administration of filarial cystatin suppressed rPhl p 5b
      induced allergen-specific Th2-responses and airway inflammation, inhibited local
      recruitment of eosinophils, reduced levels of allergen-specific IgE and down
      regulated IL-5 and IL-13 in the bronchoalveolar lavage (BAL). Ex vivo
      restimulation with cystatin of spleen cells from cystatin-treated mice induced
      the production of IL-10, while cystatin inhibited allergen-specific IL-5 and IL
      13 levels. Human PBMCs from timothy grass pollen allergic patients displayed a
      shift towards a Th1 response after treatment with cystatin. These results show
      that filarial cystatin ameliorates allergic inflammation and disease in a
      clinically relevant model of allergy. This data indicate that filarial cystatin
      has a modulatory effect on grass pollen-specific responses warranting further
      investigation of potential preventive and therapeutic options in the treatment of
      allergies.

PMID- 23174105
TI  - Stage-specific expression and antigenicity of glycoprotein glycans isolated from
      the human liver fluke, Opisthorchis viverrini.
AB  - Infection by Opisthorchis viverrini (liver fluke) is a major public health
      problem in southeastern Asia, resulting in hepatobiliary disease and
      cholangiocarcinoma. Fluke surface glycoconjugates are prominently presented to
      the host, thereby constituting a crucial immunological interface that can
      determine the parasite's success in establishing infection. Therefore, N- and O
      linked glycoprotein glycan profiles of the infective metacercarial stage and of
      the mature adult were investigated by nanospray ionisation-linear ion trap mass
      spectrometry (NSI-MS(n)). Glycan immunogenicity was investigated by
      immunoblotting with serum from infected humans. Metacercariae and adult parasites
      exhibit similar glycan diversity, although the prevalence of individual glycans
      and glycan classes varies by stage. The N-glycans of the metacercaria are mostly
      high mannose and monofucosylated, truncated-type oligosaccharides (62.7%), with
      the remainder processed to complex and hybrid type glycans (37.3%). The N-linked
      glycan profile of the adult is also dominated by high mannose and
      monofucosylated, truncated-type oligosaccharides (80.0%), with a smaller
      contribution from complex and hybrid type glycans (20.0%). At both stages,
      complex and hybrid type glycans are detected as mono-, bi-, tri-, or tetra
      antennary structures. In metacercariae and adults, O-linked glycans are detected
      as mono- to pentasaccharides. The mucin type core 1 structure, Galbeta1-3GalNAc,
      predominates in both stages but is less prevalent in the adult than in the
      metacercaria. Immunogenic recognition of liver fluke glycoproteins is reduced
      after deglycosylation but infected human serum was unable to recognise glycans
      released from peptides. Therefore, the most potent liver fluke antigenic epitopes
      are mixed determinants, comprised of glycan and polypeptide elements.

PMID- 23174107
TI  - High aldehyde dehydrogenase activity enhances stem cell features in breast cancer
      cells by activating hypoxia-inducible factor-2alpha.
AB  - High aldehyde dehydrogenase (ALDH) activity has been recognized as a marker of
      cancer stem cells (CSCs) in breast cancer. In this study, we examined whether
      inhibition of ALDH activity suppresses stem-like cell properties in a 4T1
      syngeneic mouse model of breast cancer. We found that ALDH-positive 4T1 cells
      showed stem cell-like properties in vitro and in vivo. Blockade of ALDH activity
      reduced the growth of CSCs in breast cancer cell lines. Treatment of mice with
      the ALDH inhibitor diethylaminobenzaldehyde (DEAB) significantly suppressed 4T1
      cell metastasis to the lung. Recent evidence suggests that ALDH affects the
      response of stem cells to hypoxia; therefore, we examined a possible link between
      ALDH and hypoxia signaling in breast cancer. Hypoxia-inducible factor-2alpha (HIF
      2alpha) was highly dysregulated in ALDH-positive 4T1 cells. We observed that ALDH
      was highly correlated with the HIF-2alpha expression in breast cancer cell lines
      and tissues. DEAB treatment of breast cancer cells reduced the expression of HIF
      2alpha in vitro. In addition, reduction of HIF-2alpha expression suppressed in
      vitro self-renewal ability and in vivo tumor initiation in ALDH-positive 4T1
      cells. Therefore, our findings may provide the evidence necessary for exploring a
      new strategy in the treatment of breast cancer.

PMID- 23174108
TI  - The journey from research to practice: a road less travelled.

PMID- 23174109
TI  - Assessing executive function in relation to fitness to drive: a review of tools
      and their ability to predict safe driving.
AB  - BACKGROUND/AIM: The assessment of executive functions is an integral component in
      determining fitness to drive. A structured review was conducted to identify
      assessment tools used to measure executive function in relation to driving and to
      describe these tools according to: (i) specific executive function components
      assessed; (ii) the tool's validity in predicting safe driving; and (iii) clinical
      utility. METHODS: Sixty-nine articles were reviewed, identifying 53 executive
      function tools/assessments used in driving research. Each tool was critically
      appraised and the findings were compiled in a Driving Executive Function Tool
      Guide. RESULTS: Among the 53 tools, there were 27 general assessments of
      cognition, 19 driving-specific and seven activities of daily living/instrumental
      activities of daily living assessments. No single tool measured all executive
      function components: working memory was the most common (n = 20/53). Several
      tools demonstrated strong predictive validity and clinical utility. For example,
      tools, such as the Trail Making Test and the Maze Task, have the shortest
      administration time (i.e. often less than 10 minutes) and the most easily
      accessible method of administration (i.e. pen and paper or verbal). Driving
      specific tools range from short questionnaires, such as the 10-minute Manchester
      Driving Behaviour Questionnaire, to more complex tools requiring about 45 minutes
      to administer. CONCLUSIONS AND SIGNIFICANCE OF THE STUDY: The appropriateness of
      a tool depends on the individual being assessed and on practical constraints of
      the clinical context. The Driving Executive Function Tool Guide provides useful
      information that should facilitate decision-making and selection of appropriate
      executive function tools in relation to driving.

PMID- 23174110
TI  - Contribution of occupational therapists in positive behaviour support.
AB  - AIM: Positive behaviour support employs specific strategies which aim to both
      reduce the incidence of behaviours of concern and enhance the quality of life of
      people with intellectual disabilities. This study aims to identify activities and
      experiences of occupational therapists working in behaviour support contexts to
      understand how they see their contributions in this area. METHODS: Semi
      structured interviews were undertaken with 10 occupational therapists who have
      provided behaviour support for people with intellectual disabilities. Audio
      recordings were transcribed verbatim and thematically analysed. RESULTS: Three
      major themes emerged from the interview data: contextualising and understanding
      behaviour; occupational therapy - why and how?; and 'challenges, strengths and
      expanding horizons'. CONCLUSIONS: Participants saw themselves as providing an
      occupational perspective in the delivery of behaviour support, to individuals
      with behaviour support needs. They highlighted that this was achieved utilising
      their skills and knowledge about positive behaviour support strategies. Their
      approaches were seen as drawing on: their understanding of neurological function
      and how it relates to a person's occupational engagement; combining
      occupationally focussed approaches with behavioural analysis methodology to guide
      practice; and advocating for person-centred interventions. These observations
      form the basis for exploring ways in which occupational therapists can advance
      their contributions in positive behaviour support settings.

PMID- 23174106
TI  - Next-generation sequencing in the clinic: promises and challenges.
AB  - The advent of next generation sequencing (NGS) technologies has revolutionized
      the field of genomics, enabling fast and cost-effective generation of genome
      scale sequence data with exquisite resolution and accuracy. Over the past years,
      rapid technological advances led by academic institutions and companies have
      continued to broaden NGS applications from research to the clinic. A recent crop
      of discoveries have highlighted the medical impact of NGS technologies on
      Mendelian and complex diseases, particularly cancer. However, the ever-increasing
      pace of NGS adoption presents enormous challenges in terms of data processing,
      storage, management and interpretation as well as sequencing quality control,
      which hinder the translation from sequence data into clinical practice. In this
      review, we first summarize the technical characteristics and performance of
      current NGS platforms. We further highlight advances in the applications of NGS
      technologies towards the development of clinical diagnostics and therapeutics.
      Common issues in NGS workflows are also discussed to guide the selection of NGS
      platforms and pipelines for specific research purposes. 

PMID- 23174111
TI  - Better Access to Mental Health program: influence of mental health occupational
      therapy.
AB  - BACKGROUND/AIM: The Better Access to Mental Health program has enabled eligible
      occupational therapists to provide services to people with a mental health
      condition. No studies have yet reported the influence of occupational therapy
      under this scheme. The aim of this study was to investigate whether attending an
      occupational therapist under this initiative influences change in psychological
      distress of clients as measured by the Kessler Psychological Distress Scale
      (K10). METHOD: A quasi-experimental pretest-posttest design, using pre-existing
      data collected in the process of regular treatment was used. Data from a total of
      31 clients (mean = 17.13 years, SD = 3.603) were accessed for this study. Pre-
      and post-intervention scores on the K10 were used to determine if psychological
      distress had changed over the course of intervention. RESULTS: Highly significant
      improvements (P < 0.001) were found between the K10 pre-intervention score (mean
      = 25.68, SD = 9.944) and the K10 post-intervention score (mean = 21.00, SD =
      9.212). Male K10 post-intervention scores (mean = 17.64, SD = 5.3) significantly
      improved (P = 0.05), whereas results for females were not statistically
      significant. Medication use, diagnosis, age, number of sessions and prior contact
      with health services did not influence the results. Results from specific
      evidence-based interventions were not able to be considered in this study.
      CONCLUSION: The results of this study demonstrate effectiveness of occupational
      therapy services for adolescents and provide support for the ongoing
      participation of occupational therapists in this scheme.

PMID- 23174112
TI  - New graduate occupational therapists feelings of preparedness for practice in
      Australia and Aotearoa/New Zealand.
AB  - AIM: The development of competent future allied health professionals through
      academic programmes, professional support and practical education is continually
      evolving. The aim of this study was to explore the feelings of newly graduated
      occupational therapists in Australia and Aotearoa/New Zealand regarding their
      education and work preparedness. METHODS: Newly graduated occupational therapists
      from Australia (n = 178) and Aotearoa/New Zealand (n = 53) who had completed
      their occupational therapy studies in 2007 were recruited. Participants completed
      an online survey which explored their preparedness for work; based on
      professional competencies. RESULTS: Most newly graduated occupational therapists
      felt somewhat prepared for practice. However, only 17.1% of Australian new
      graduates, and even fewer (8.5%) of Aotearoa/New Zealand new graduates felt very
      well prepared. Participants felt more prepared for the competencies required for
      'managing inwards' (including interpersonal skills) and less prepared for those
      required for 'managing outwards' (including evidence-based practice).
      CONCLUSIONS: This study provides the first international comparison into the
      feelings of competence and preparedness for practice of new graduates of
      occupational therapy from Australia and Aotearoa/New Zealand. Given the
      importance of competencies, such as evidence-based practice to the progress of
      the profession, there is a need to further explore methods to increase feelings
      of preparedness in these areas.

PMID- 23174113
TI  - Coordination difficulties and self-esteem: a review and findings from a New
      Zealand survey.
AB  - AIMS: Children and adolescents with significant coordination difficulties have
      consistently been found to have lower self-esteem in relation to athletic
      competence and physical ability. However, findings in relation to global self
      esteem have been mixed. This study aimed to investigate the self-esteem of
      children and adolescents with a diagnosis of dyspraxia in a large New Zealand
      sample. METHODS: A confidential postal questionnaire was sent to all members of
      the Dyspraxia Support Group of New Zealand. Children and adolescents aged seven
      to 18 years with a diagnosis of dyspraxia were asked to complete the Piers-Harris
      Children's Self-Concept Scale 2nd edition (PHCSCS-2), while parents were asked
      about a range of factors which might affect self-esteem including possible
      coexisting conditions. RESULTS: There was a response rate of 20% with 75 valid
      responses. Coexisting conditions were common including 50.7% with a diagnosis of
      dyslexia or another learning disorder. Children and adolescents with dyspraxia
      scored significantly lower than PHCSCS-2 norms on the physical appearance and
      attributes, intellectual and school status and popularity subscales and also the
      PHCSCS-2 total score, indicating lower global self-esteem. CONCLUSIONS: This
      study strengthens the evidence that an association exists in children and
      adolescents between having significant coordination difficulties and lower global
      self-esteem.

PMID- 23174114
TI  - Changes and challenges in higher education: what is the impact on fieldwork
      education?

PMID- 23174115
TI  - Single subject experimental design study demonstrated Cognitive Orientation to
      daily Occupational Performance (CO-OP) improved performance of self-selected
      goals in adults with chronic stroke.

PMID- 23174116
TI  - Weighted vests did not improve competing behaviours or joint attention of 2 year
      olds with Autism Spectrum Disorder (ASD).

PMID- 23174118
TI  - A mass spectrometry-based plasma protein panel targeting the tumor
      microenvironment in patients with breast cancer.
AB  - Proteins secreted or shed by cancerous cells are seen as a rich source of
      biomarkers and novel therapeutic targets. Recently, the importance of the tumor
      microenvironment, which comprises the surrounding non-tumor cells, has received
      increased attention for its role in tumor progression. We developed a targeted
      proteomics assay to monitor a panel of plasma proteins postulated to be present
      in the tumor microenvironment. The plasma of 76 breast cancer patients was
      depleted of abundant circulating proteins, enzymatically digested and labeled by
      reductive methylation. The labeled digests were analyzed by tandem mass
      spectrometry using a multiple reaction monitoring acquisition method. The protein
      targets were correlated with the tumor characteristics, the extent of the disease
      and the clinical staging of the patients. Linear discriminant analysis revealed
      that infiltrating ductal and invasive mammary breast carcinomas could be grouped
      based on distinctive peptide levels of fibronectin, clusterin, gelsolin and alpha
      1-microglobulin/Inter-alpha-trypsin inhibitor light chain precursor (AMBP). These
      proteins have been previously associated with breast cancer at the tissue level,
      however, this is the first study to measure plasma levels of these proteins and
      correlate these levels with clinical features. Significant variability was seen
      between unique peptides belonging to the same protein. This article is part of a
      Special Issue entitled: From protein structures to clinical applications.

PMID- 23174119
TI  - Proteomic analysis of the phenotype of the scaleless wings mutant in the
      silkworm, Bombyx mori.
AB  - A scaleless wing mutant of silkworm, Bombyx mori, has much fewer scales than wild
      type (WT). The scaleless phenotype was associated with tracheal system
      developmental deficiency and excessive apoptosis of scale cells. In this study,
      the wing discs proteins of WT and scaleless during pupation were studied using 2
      DE and mass spectrometry. Of the 99 identified protein spots, four critical
      differentially expressed proteins between WT and scaleless were further verified
      using Q-PCR. At the first day of pupation (P0) in WT, imaginal disk growth factor
      (IDGF) was upregulated, whereas actin-depolymerizing factor 1 (ADF1) and profilin
      (PFN), which associated with cellular motility and cytoplasmic extension, were
      downregulated. We speculated their coaction counteracts the correct organization
      of the tracheal system in wing disc. Thiol peroxiredoxin (TPx) was upregulated in
      scaleless at P0, but its mRNA higher expression occurred in the day before
      pupation (S4). TPx could inhibit the formation of hydrogen peroxide, preventing
      the release of cytochrome C and activation of the caspase family protease. Its
      higher expression in scaleless was responsible for the apoptosis of scale cells
      delayed. The results provide further evidence that the scaleless phenotype was
      related to the tracheal system developmental deficiency and excessive apoptosis
      of scale cells.

PMID- 23174120
TI  - DNA methylation pattern in mouse oocytes and their in vitro fertilized early
      embryos: effect of oocyte vitrification.
AB  - This study was conducted to investigate the pattern of DNA methylation in
      vitrified-thawed mouse oocytes and their in vitro fertilized early embryos.
      Firstly, mouse oocytes at metaphase II (MII) stage of meiosis were allocated
      randomly into three groups: (1) untreated (control); (2) exposed to vitrification
      solution without being plunged into liquid nitrogen (toxicity); or (3) vitrified
      by open-pulled straw (OPS) method (vitrification). Oocytes from all three groups
      were fertilized subsequently in vitro. The level of DNA methylation in the MII
      oocytes and their early embryos was then examined by immunofluorescence using an
      anti-5-methylcytosine (anti-5-MeC) monoclonal antibody and fluorescein
      isothiocyanate (FITC)-conjugated goat anti-mouse IgG. Developmental rates to 2
      cell embryos (62.28%) and blastocysts (43.68%) of the vitrified-thawed oocytes
      were lower (P < 0.01) than those of fresh oocytes (81.47%, 61.99%) and
      vitrification solution treated (79.20%, 60.04%) oocytes. DNA methylation (as
      reflected by 5-MeC fluorescence intensity) in the vitrification group was less (P
      < 0.01) for MII oocyte and 2- to 8-cell stages compared with that in the control
      and toxicity groups. Accordingly, a reduction in global genomic methylation due
      to vitrification of MII oocytes may result in compromised in vitro developmental
      potential in early mouse embryos.

PMID- 23174121
TI  - Extensive histone post-translational modification in honey bees.
AB  - Histone post-translational modifications (PTMs) play a key role in regulating a
      variety of cellular processes including the establishment, maintenance and
      reversal of transcriptional programmes in eukaryotes. However, little is known
      about such modifications in the economically and ecologically important insect
      pollinator, the honey bee (Apis mellifera). Using mass spectrometry approaches,
      we show that histone H3.1, H3.3 and H4 of the honey bee are extensively modified
      by lysine acetylation and lysine methylation. We analysed histones isolated from
      queen ovaries and 96 hr-old larvae, in toto we quantified 23 specific
      modification states on 23 distinct peptides. In addition, we have identified and
      characterised patterns of histone PTMs that reside on the same peptide,
      generating detailed combinatorial information. Overall, we observed similar
      profiles of histone PTMs in both samples, with combinatorial patterns of lysine
      methylations on H3K27 and H3K36 more frequently identified in histones extracted
      from queen ovaries than from larvae. To our knowledge, this comprehensive dataset
      represents the first identification and quantitation of histone PTMs in this
      eusocial insect and emerging epigenetic model.

PMID- 23174122
TI  - Repurposing buspirone for drug addiction treatment.

PMID- 23174123
TI  - Abstracts of the International Network on Brief Interventions for Alcohol and
      Other Drugs (INEBRIA) Meeting 2011. Boston, Massachusetts, USA. September 21-23,
      2011.

PMID- 23174124
TI  - Vitamin D status in Chinese pregnant women and their newborns in Beijing and
      their relationships to birth size.
AB  - OBJECTIVE: To evaluate the prevalence of vitamin D deficiency in pregnant women
      and their newborns in Beijing, China and the influence of vitamin D deficiency on
      birth size. DESIGN: A cross-sectional study. SETTING: Data were collected from
      pregnant women who delivered during April to May 2010 at 306 Hospital of PLA in
      Beijing, China. SUBJECTS: Participants in the study were seventy healthy
      nulliparous pregnant women with singleton pregnancies who delivered healthy
      babies at full term and their newborns. RESULTS: Severe vitamin D deficiency (25
      hydroxyvitamin D (25(OH)D) < 25 nmol/l) was detected in 54.5 % of mothers and
      46.6 % of newborns. Neither mothers nor newborns had serum 25(OH)D concentrations
      that reached the normal level (>75 nmol/l). The concentration of 25(OH)D in
      mothers was positively correlated with that in cord blood (r = 0.89, P < 0.001).
      Newborns of mothers with severe vitamin D deficiency had lower birth length and
      birth weight. The head circumference and birth weight were lower in vitamin D
      deficient newborns. CONCLUSIONS: The study indicates that pregnant women and
      neonates residing in Beijing are at high risk of vitamin D deficiency. Neonatal
      25(OH)D concentrations are dependently related to maternal 25(OH)D levels.
      Maternal and neonatal vitamin D status influences newborn size.

PMID- 23174125
TI  - Restoring fertility after ovarian tissue cryopreservation: a half century of
      research.
AB  - Tissue transplantation and in vitro ovarian follicle culture have been
      investigated as alternative techniques to restore fertility in young women who
      are facing fertility-threatening diseases or treatments following ovarian tissue
      cryopreservation. Although transplants of fresh or frozen ovarian tissue have
      successfully yielded healthy live births in different species including humans,
      the risks of reintroducing cancer cells back into the patient, post treatment,
      have limited its clinical purpose. The in vitro ovarian follicle culture
      minimizes these risks and provides a way to harvest more mature oocytes, however
      its clinical translation has yet to be determined. Not only is it possible for
      tissue cryopreservation to safeguard fertility in cancer patients, this technique
      also allows the maintenance of germplasm banks for animals of high commercial
      value or for those animals that are at risk of extinction. Given the importance
      of managing female genetic material, this paper reviews the progress of the
      methods used to preserve and restore female fertility in different species to
      demonstrate the results obtained in the past 50 years of research, the current
      achievements and the future directions on this field.

PMID- 23174127
TI  - Transferring information to an out-of-hours primary care service for patients
      with palliative care needs: an action research study to improve the use of
      handover forms.
AB  - AIM: To work with service users and providers to optimise the design and
      implementation of handover forms to support the transfer of information between
      daytime and out-of-hours primary care services for patients with palliative care
      needs. BACKGROUND: There is a need for improved informational continuity between
      daytime and out-of-hours primary care services for patients with palliative care
      needs. Research suggests that while handover forms are vital to ensure continuity
      of care, they remain underused for such patients. Audit work in an out-of-hours
      primary care service in South West England identified that their current system
      of handover forms was underused. METHODS: An action research study consisting of
      two phases was undertaken. In phase one, the views of general practitioners and
      nurses working in the out-of-hours and daytime primary care services (29 health
      professionals) in Devon (population c.1.4 million) and patients with palliative
      care needs and their carers (8 participants) were investigated using qualitative
      interviews and focus group methods. Participants' views on the content and use of
      handover forms, and of the systems supporting their generation were sought. In
      phase two, additional feedback from the health professional stakeholder groups
      was collected and collaborative work undertaken with the out-of-hours service to
      implement recommendations emerging from the qualitative research. Findings
      Respondents identified variable use of handover forms and inconsistent practice
      in terms of: who was responsible for generating and updating forms; when and
      where they were discussed in primary care; the criteria used to define which
      patient needed a form; and the information forms should contain. There was
      uncertainty about how handover forms were used by the out-of-hours service and
      concerns about incomplete access to forms for certain groups of staff. An action
      plan to improve the existing system was developed. This included distribution of
      educational materials (desktop guide, newsletter) to key stakeholders, and the
      modification of information systems to facilitate the updating of messages and
      the accessibility of electronic records for previously under-served staff.

PMID- 23174126
TI  - [Alexandre Reydellet, Navy surgeon (1793-1859): a life devoted to fighting
      smallpox at Reunion Island].
AB  - After reviewing the history of smallpox throughout the world and of the
      techniques used to try to prevent it (variolation and then Jenner's vaccine), we
      describe the epidemics that reached in the Indian Ocean between 1729 and 1859.
      Alexandre Reydellet, a Navy surgeon under Naoleon, arrived in Reunion in 1815 and
      stayed until his death in 1859. His energetic vaccination campaigns and their
      results are depicted.

PMID- 23174128
TI  - Report on the 4'th scientific meeting of the "Verein zur Forderung des
      Wissenschaftlichen Nachwuchses in der Neurologie" (NEUROWIND e.V.) held in
      Motzen, Germany, Nov. 2'nd - Nov. 4'th, 2012.
AB  - From November 2nd - 4th 2012, the 4th NEUROWIND e.V. meeting was held in Motzen,
      Brandenburg, Germany. Again more than 60 participants, predominantly at the
      doctoral student or postdoc level, gathered to share their latest findings in the
      fields of neurovascular research, neurodegeneration and neuroinflammation. Like
      in the previous years, the symposium provided an excellent platform for
      scientific exchange and the presentation of innovative projects in the
      stimulating surroundings of the Brandenburg outback. This year's keynote lecture
      on the pathophysiological relevance of neuronal networks was given by Christian
      Gerloff, Head of the Department of Neurology at the University Clinic of Hamburg
      Eppendorf. Another highlight of the meeting was the awarding of the NEUROWIND
      e.V. prize for young scientists working in the field of experimental neurology.
      The award is donated by the Merck Serono GmbH, Darmstadt, Germany and is endowed
      with 20.000 Euro. This year the jury decided unanimously to adjudge the award to
      Michael Gliem from the Department of Neurology at the University Clinic of
      Dusseldorf (group of Sebastian Jander), Germany, for his outstanding work on
      different macrophage subsets in the pathogenesis of ischemic stroke published in
      the Annals of Neurology in 2012.

PMID- 23174129
TI  - 'We eat together; today she buys, tomorrow I will buy the food': adolescent best
      friends' food choices and dietary practices in Soweto, South Africa.
AB  - OBJECTIVE: To explore if and how female adolescents engage in shared eating and
      joint food choices with best friends within the context of living in urban
      Soweto, South Africa. DESIGN: A qualitative, exploratory, multiple case study was
      conducted using semi-structured duo interviews of best friend pairs to ascertain
      their eating patterns, friendship and social interactions around dietary habits.
      SETTING: Participants were recruited from three high schools in the urban
      township of Soweto, South Africa. SUBJECTS: Fifty-eight female adolescents
      (twenty-nine friend pairs) still in high school (mean age of 18 years) were
      enrolled. RESULTS: Although overweight rates were high, no association between
      friends was found; neither did friends share dieting behaviours. Both at school
      and during visits to the shopping mall, foods were commonly shared and money
      pooled together by friends to make joint purchases. Some friends carefully
      planned expenditures together. Foods often bought at school were mostly
      unhealthy. Availability, price and quality were reported to affect choice of
      foods purchased at school. Preference shaped joint choices within the shopping
      mall environment. CONCLUSIONS: Food sharing practices should be investigated in
      other settings so as to identify specific behaviours and contexts for targeted
      and tailored obesity prevention interventions. School-based interventions
      focusing on price and portion size should be considered. In the Sowetan context,
      larger portions of healthy food may improve dietary intake of fruit and
      vegetables where friends are likely to share portions.

PMID- 23174130
TI  - Interpersonal conflict strategies and their impact on positive symptom remission
      in persons aged 55 and older with schizophrenia spectrum disorders.
AB  - BACKGROUND: Although interpersonal interactions are thought to affect
      psychopathology in schizophrenia, there is a paucity of data about how older
      adults with schizophrenia manage interpersonal conflicts. This paper examines
      interpersonal conflict strategies and their impact on positive symptom remission
      in older adults with schizophrenia spectrum disorders. METHODS: The schizophrenia
      group consisted of 198 persons aged 55 years and over living in the community who
      developed schizophrenia before age 45. A community comparison group (n = 113) was
      recruited using randomly selected block-groups. Straus' Conflict Tactics Scale
      (CTS) was used to assess the ways that respondents handled interpersonal
      conflicts. RESULTS: Seven conflict management subscales were created based on a
      principal component analysis with equamax rotation of items from the CTS. The
      order of the frequency of the tactics that was used was similar for both the
      schizophrenia and community groups. Calm and Pray tactics were the most commonly
      used, and the Violent and Aggressive tactics were rarely utilized. In two
      separate logistic regression analysis, after controlling for confounding
      variables, positive symptom remission was found to be associated significantly
      with both the Calm and Pray subscales. CONCLUSIONS: The findings suggest that
      older persons with schizophrenia approximate normal distribution patterns of
      conflict management strategies and the most commonly used strategies are
      associated with positive symptom remission.

PMID- 23174131
TI  - Identification of alpha-1 acid glycoprotein (AGP) as a potential marker of
      impaired growth in the newborn piglet.
AB  - Two studies were conducted to investigate the relationship between circulating
      levels of haptoglobin and alpha-1 acid glycoprotein (AGP) and growth in neonatal
      pigs. Circulating serum AGP, but not haptoglobin, was higher (P<0.001) in newborn
      runts than average-sized littermates. At 1 and 3 weeks, AGP and haptoglobin were
      similar among control and runt piglets. To determine the possible association
      between AGP and growth rate, blood was collected between the first and second day
      after birth in piglets from 10 average litters. Birthweight was positively
      correlated with growth rate through 21 days (linear regression correlation
      coefficient (CC), 0.43 (P<0.006); 0.299 (P<0.003) in males and females,
      respectively). Plasma AGP at birth was negatively correlated with growth (CC, 
      0.429 (P<0.006); -0.351 (P<0.01) in males and females, respectively). When AGP
      was calculated on a per kg birthweight basis, the CC with growth improved by 25
      and 34% in males and females, respectively, compared with birthweight alone.
      Haptoglobin in blood was not correlated with growth. These data suggest that AGP
      at birth is reflective of growth conditions in utero or fetal maturation and may
      serve as an early predictive biomarker for pre-weaning growth rate. 

PMID- 23174132
TI  - Seroprevalence of certain bacterial and viral infections among the Irula tribal
      population of Marakkanam, Tamil Nadu state, India.
AB  - AIM: Seroprevalence study in Irula tribe of Marakkanam, Tamil Nadu State was
      carried out for certain bacterial (typhoid, syphilis and leptospirosis) and viral
      infection (hanta, hepatitis B and human immunodeficiency virus (HIV)). RESULT:
      Highest seroprevalence was observed for leptospirosis (61.1%) followed by,
      hepatitis B virus surface antigen (11.11%), syphilis (9.72%), typhoid (8.33%),
      hantavirus (6.9%) and HIV (2.77%). OBSERVATION: The seroprevalence of
      leptospirosis and hantavirus may be attributed to their professional exposure to
      rodent that they catch in the open field and the syphilis, hepatitis B and HIV
      prevalence may be related to their sexual behavior and social customs.

PMID- 23174133
TI  - [Long fingers articular fractures treatment by glued traction].
AB  - Comminuted articular fractures of the fingers are a real surgical challenge. Many
      surgical treatments are proposed, but despite their complexity, their results are
      often unsatisfactory. We describe a simple and functional treatment intended to
      ensure these articular fractures heal in the right position. The material used in
      this technique is inexpensive and easily available.

PMID- 23174134
TI  - Development of imatinibmesylate-induced interstitial lung disease 2 weeks after
      discontinuation of the treatment: a case report.
AB  - BACKGROUND: Imatinibmesylate (imatinib) is a small molecule tyrosine kinase
      inhibitor administered to patients with chronic myelogenous leukemia and
      gastrointestinal stromal tumor. Although imatinib-associated interstitial lung
      disease is uncommon, a few cases have been reported so far. However, in all these
      cases interstitial lung disease developed during the use of imatinib. The present
      case is the first report of imatinib-induced interstitial lung disease developing
      after discontinuation of the drug. CASE PRESENTATION: A 51-year-old woman was
      administered oral imatinib for gastrointestinal stromal tumor. Ten weeks later,
      imatinib was discontinued because of facial edema. On this occasion, chest
      radiography showed no abnormal findings. However, 2 weeks after discontinuation
      of imatinib, she developed fever, dry cough, and dyspnea. Chest radiography and
      computed tomography showed diffuse interstitial infiltrates in both lungs.
      Examination of bronchoalveolar lavage fluid showed an increased proportion of
      lymphocytes. Imatinib-induced interstitial lung disease was suspected, because no
      other cause was evident. After administration of corticosteroids, her clinical
      condition and chest radiographic findings improved. CONCLUSION: We report a
      unique case of imatinib-induced interstitial lung disease that developed 2 weeks
      after discontinuation of the drug. Physicians should consider occurrence of
      imatinib-induced interstitial lung disease even after discontinuation of the
      drug.

PMID- 23174135
TI  - Physicians' practice and familiarity with treatment for agitation associated with
      dementia in Israeli nursing homes.
AB  - BACKGROUND: To clarify physicians' actual practice in treating agitation in the
      nursing home and to elucidate the relationship between background factors,
      familiarity with interventions, and practice. METHODS: A survey of actual
      practice for agitation in persons with dementia was administered to 67 physicians
      aged 31-70+ working in nursing homes in Israel. Questionnaires were administered
      by personal interview, self-completed, or a combination of the two. RESULTS:
      Psychotropic medications are prescribed by 92.5% of physicians for treating
      agitation, most notably, Haloperidol (39%). Non-pharmacological treatment was
      also reported to be common, though to a lesser extent, with environmental change
      being the most prevalent non-pharmacological intervention. Generally, physicians
      showed low familiarity levels with non-pharmacological interventions, with higher
      levels noted for physicians with a specialty in geriatrics compared to those who
      were non-specialized. Physicians who were non-Israeli and younger also reported
      higher familiarity levels compared to their respective counterparts (i.e. Israeli
      and older) but this difference did not reach significance. CONCLUSION: The
      findings indicate that, despite current guidelines, psychotropic medications are
      the treatment of choice among nursing home physicians in Israel. While rates of
      use of non-pharmacological interventions are substantial, their in-practice
      application may be hindered by lack of familiarity as well as system barriers.
      The results have implications for system and education changes.

PMID- 23174136
TI  - College cafeteria snack food purchases become less healthy with each passing week
      of the semester.
AB  - OBJECTIVE: Snacks, stress and parties all contribute to the weight gain - the
      elusive 'Freshman 15' - that some college-goers unfortunately experience. The
      present study examines how a' la carte snack choice changes on a university
      campus during each progressing week of the academic calendar. DESIGN: How a' la
      carte snack choices change on a university campus with each progressing week of
      the academic calendar was examined. SETTING: The data were collected from three
      large cafeterias (or dining halls) on Cornell University's campus during four
      semesters (Fall 2006, Spring 2007, Fall 2007 and Spring 2008), for 18 weeks in
      each semester. SUBJECTS: After the a' la carte snack items were divided into
      healthy snacks and unhealthy snacks, the percentage share for each food category
      was calculated. RESULTS: Within each semester, the unhealthy snack food choices
      increased consistently by 0?4% per week (b50?00418, P,0?01). Furthermore, a sharp
      (8 %) increase occurred in the final two weeks of the semester. In contrast,
      healthy snack food choices decreased by almost 4% (b520?0408, P,0?01) in the
      final two weeks during the fall semester. CONCLUSIONS: These results demonstrate
      an increased demand for hedonic, or unhealthy, snack foods as the college
      semester progresses and in particular at the very end of the semester. To counter
      this tendency towards unhealthy snacking, cafeterias and stores should make extra
      effort to promote healthy alternatives during the later weeks of the semester.

PMID- 23174137
TI  - Adverse event reporting in adult intensive care units and the impact of a
      multifaceted intervention on drug-related adverse events.
AB  - BACKGROUND: Adverse events (AEs) frequently occur in intensive care units (ICUs)
      and affect negatively patient outcomes. Targeted improvement strategies for
      patient safety are difficult to evaluate because of the intrinsic limitations of
      reporting crude AE rates. Single interventions influence positively the quality
      of care, but a multifaceted approach has been tested only in selected cases. The
      present study was designed to evaluate the rate, types, and contributing factors
      of emerging AEs and test the hypothesis that a multifaceted intervention on
      medication might reduce drug-related AEs. METHODS: This is a prospective,
      multicenter, before-and-after study of adult patients admitted to four ICUs
      during a 24-month period. Voluntary, anonymous, self-reporting of AEs was
      performed using a detailed, locally designed questionnaire. The temporal impact
      of a multifaceted implementation strategy to reduce drug-related AEs was
      evaluated using the risk-index scores methodology. RESULTS: A total of 2,047 AEs
      were reported (32 events per 100 ICU patient admissions and 117.4 events per
      1,000 ICU patient days) from 6,404 patients, totaling 17,434 patient days. Nurses
      submitted the majority of questionnaires (n = 1,781, 87%). AEs were eye-witnessed
      in 49% (n = 1,003) of cases and occurred preferentially during an elective
      procedure (n = 1,597, 78%) and on morning shifts (n = 1,003, 49%), with a peak
      rate occurring around 10 a.m. Drug-related AEs were the most prevalent (n = 984,
      48%), mainly as a consequence of incorrect prescriptions. Poor communication
      among caregivers (n = 776) and noncompliance with internal guidelines (n = 525)
      were the most prevalent contributing factors for AE occurrence. The majority of
      AEs (n = 1155, 56.4%) was associated with minimal, temporary harm. Risk-index
      scores for drug-related AEs decreased from 10.01 +/- 2.7 to 8.72 +/- 3.52
      (absolute risk difference 1.29; 95% confidence interval, 0.88-1.7; p < 0.01)
      following the introduction of the intervention. CONCLUSIONS: AEs occurred in the
      ICU with a typical diurnal frequency distribution. Medication-related AEs were
      the most prevalent. By applying the risk-index scores methodology, we were able
      to demonstrate that our multifaceted implementation strategy focused on
      medication-related adverse events allowed to decrease drug related incidents.

PMID- 23174138
TI  - Involvement of sperm plasma membrane and cytoskeletal proteins in human male
      infertility.
AB  - OBJECTIVE: To assess the physicochemical characteristics of sperm plasma membrane
      and to evaluate the immunohistochemical expression of transmembrane and
      cytoskeletal proteins in spermatozoa isolated from normospermic fertile donors
      and asthenozoospermic infertile patients. DESIGN: Case-control study. SETTING:
      Academic male infertility center. PATIENT(S): Twenty-five infertile patients
      affected by idiopathic asthenozoospermia and 21 age-matched normospermic fertile
      donors. INTERVENTION(S): Sperm parameters were evaluated; membrane fluidity and
      hydration studies, and immunohistochemical analysis were performed in isolated
      spermatozoa. MAIN OUTCOME MEASURE(S): Semen analyses to ascertain volume, sperm
      count, motility, and morphology; then membrane fluidity and hydration studies and
      immunohistochemical analysis were performed on isolated spermatozoa. RESULT(S):
      Spermatozoa from the asthenozoospermic group exhibited a reduced fluidity at the
      lipid-water interface level, an increased fluidity of the deeper portion of the
      bilayer, and a lower plasma membrane hydration than normospermic cells. Moreover,
      the immunohistochemical expression of ezrin, Cdc42, CD9, F-actin, and beta
      tubulin was higher in normospermic samples. CONCLUSION(S): Our results together
      assume that a cytoskeletal reorganization induced by a disturbance in the
      physicochemical features of sperm plasma membrane, and potentially mediated by
      ezrin, Cdc42, and tetraspanin CD9, could have a role in idiopathic
      asthenozoospermia.

PMID- 23174139
TI  - [Comparison of Kinyoun, auramine O, and Ziehl-Neelsen staining for diagnosing
      tuberculosis at the National Tuberculosis Center in Burkina Faso].
AB  - CONTEXT: This study was conducted at the National Tuberculosis Center in Burkina
      Faso from October 2007 through May 2008. OBJECTIVE: Our objective was to compare
      the diagnostic performance of three staining methods: Kinyoun, auramine O, and
      Ziehl-Neelsen. METHODS: Ziehl-Neelsen staining served as the reference method to
      assess the diagnostic performance of Kinyoun and auramine O staining. In all, 616
      sputum smears from 233 patients were read with each method to detect acid-fast
      bacilli. SPSS was used for data analysis. RESULTS: The results of auramine O
      staining showed positive diagnoses in 15.9% of the samples; sensitivity was 100%,
      specificity 95.6%, and the positive and negative predictive values 75.7% and 100%
      respectively. Kinyoun staining produced a positive diagnosis rate of 12%,
      sensitivity of 96.4%, specificity of 99.5%, and positive and negative predictive
      values of 96.4% and 99.5%. CONCLUSION: Our study indicates that auramine O
      staining had a better sensitivity for detecting acid-fast bacilli than Kinyoun
      staining. Accordingly, the use of auramine O staining should increase the
      detection rate for pulmonary tuberculosis in Burkina Faso.

PMID- 23174140
TI  - Inactivation of encapsulated cells and their therapeutic effects by means of TGL
      triple-fusion reporter/biosafety gene.
AB  - The immobilization of cells within alginate-poly-l-lysine-alginate (APA)
      microcapsules has been demonstrated to be an effective technology design for long
      term delivery of therapeutic products. Despite promising advances, biosafety
      aspects still remain to be improved. Here, we describe a complete
      characterization of the strategy based on TGL triple-fusion reporter gene--which
      codifies for Herpes Simplex virus type 1 thymidine-kinase (HSV1-TK), green
      fluorescent protein (GFP) and Firefly Luciferase--(SFG(NES)TGL) to inactivate
      encapsulated cells and their therapeutic effects. Myoblasts genetically
      engineered to secrete erythropoietin (EPO) were retroviraly transduced with the
      SFG(NES)TGL plasmid to further characterize their ganciclovir (GCV)-mediated
      inactivation process. GCV sensitivity of encapsulated cells was 100-fold lower
      when compared to cells plated onto 2D surfaces. However, the number of cells per
      capsule and EPO secretion decayed to less than 15% at the same time that
      proliferation was arrested after 14 days of GCV treatment in vitro. In vivo, ten
      days of GCV treatment was enough to restore the increased hematocrit levels of
      mice implanted with encapsulated TGL-expressing and EPO-secreting cells.
      Altogether, these results show that TGL triple-fusion reporter gene may be a good
      starting point in the search of a suitable biosafety strategy to inactivate
      encapsulated cells and control their therapeutic effects.

PMID- 23174141
TI  - Nanocarriers for the targeted treatment of ovarian cancers.
AB  - Ovarian cancer is the leading cause of death from gynecological malignancies
      worldwide. Although the majority of tumors initially respond to standard
      treatments combining surgery and chemotherapy with platinum based chemotherapy,
      frequent recurrence and subsequent acquired chemoresistance are responsible for
      the therapeutic failure, leading to an overall 5 years survival rate of 30%.
      Considering the usual initial sensitivity of the ovarian tumors to chemotherapy,
      over the past decade efforts have been focused over the past decade to cure
      ovarian cancer using the currently available chemotherapeutic agents in various
      combinations, dosages, schedules (durations and/or routes of administration).
      However, with such a systemic chemotherapeutic approach, considerable limitations
      exist including toxicities to healthy tissues and low achievable drug
      concentrations at tumor sites. Considerable efforts are implemented to engineer
      systems capable of ferrying large doses of cytotoxic agents specifically into
      targeted malignant cells while sparing healthy cells. The purpose of the present
      review is to index the main targeted colloidal systems used for drug delivery to
      ovarian tumors. These nanocarriers will be analyzed by citing examples of their
      use in preclinical development.

PMID- 23174142
TI  - Docetaxel-loaded thermoresponsive conjugated linoleic acid-incorporated poloxamer
      hydrogel for the suppression of peritoneal metastasis of gastric cancer.
AB  - We evaluated the potential of a thermoresponsive hydrogel consisting of
      conjugated linoleic acid-coupled Pluronic F-127 (Plu-CLA) as a controlled
      release, intraperitoneal delivery system for docetaxel with the aim of treating
      peritoneal dissemination of gastric cancer. Previously, we established a
      peritoneal metastasis model that involves the injection of BALB/c mice with TMK1
      human gastric cancer cells. One week after the TMK1 cells were injected, the mice
      were injected intraperitoneally with docetaxel alone or docetaxel-loaded Plu-CLA.
      Tumor progression and response to therapy were monitored by micro-positron
      emission tomography. The total number of peritoneal tumors and the ascites volume
      were also measured. Compared with docetaxel alone, the combination of docetaxel
      and Plu-CLA (docetaxel-Plu-CLA) significantly and synergistically reduced tumor
      cell survival. Docetaxel-Plu-CLA showed excellent anti-tumor activity, inducing
      apoptosis more potently than docetaxel alone. Docetaxel-Plu-CLA also
      significantly reduced the number of peritoneal metastatic nodules and increased
      survival in the peritoneal gastric cancer xenograft model. Our results show that
      intraperitoneal administration of docetaxel-Plu-CLA synergistically inhibits
      peritoneal metastasis and prolongs survival in a peritoneal gastric cancer model.
      Therefore, Plu-CLA is a potential intraperitoneal-route carrier for hydrophobic
      docetaxel for the effective treatment of peritoneal metastatic gastric cancer.

PMID- 23174143
TI  - Antimicrobial activity of a ferrocene-substituted carborane derivative targeting
      multidrug-resistant infection.
AB  - Multidrug resistance (MDR) of bacteria is still an unsolved serious problem to
      threaten the health of human beings. Developing new antibacterial agents,
      therefore, are urgently needed. Herein, we have explored the possibility to
      design and synthesize some novel antibacterial agents including ferrocene
      substituted carborane derivative (Fc(2)SBCp(1)) and have evaluated the relevant
      antibacterial action against two clinical common MDR pathogens (i.e., Gram
      positive Staphylococcus aureus and Gram-negative Pseudomonas aeruginosa) in vitro
      and in vivo. The results demonstrate that in vitro antimicrobial activity of
      Fc(2)SBCp(1) could be gradually transformed into a bactericidal effect from a
      bacteriostatic effect with the increasing concentration of the active carborane
      derivative, which can also prevent biofilm formation at concentrations below MIC
      (i.e., minimal inhibitory concentration). Biocompatibility studies indicate that
      there exists no/or little toxic effect of Fc(2)SBCp(1) on normal cells/tissues
      and leads to little hemolysis. In vivo studies illustrate that the new carborane
      derivative Fc(2)SBCp(1) is highly effective in treating bacteremia caused by S.
      aureus and P. aeruginosa as well as interstitial pneumonia caused by S. aureus.
      This raises the possibility for the potential utilization of the new ferrocene
      substituted carborane derivatives as promising antibacterial therapeutic agents
      against MDR bacterial infections in future clinical applications.

PMID- 23174144
TI  - Histopathological effects of waterborne copper nanoparticles and copper sulphate
      on the organs of rainbow trout (Oncorhynchus mykiss).
AB  - It is unclear whether copper nanoparticles are more toxic than traditional forms
      of dissolved copper. This study aimed to describe the pathologies in gill, gut,
      liver, kidney, brain and muscle of juvenile rainbow trout, Oncorhynchus mykiss,
      exposed in triplicate to either a control (no added Cu), 20 or 100 MUg l(-1) of
      either dissolved Cu (as CuSO(4)) or Cu-NPs (mean primary particle size of 87 +/-
      27 nm) in a semi-static waterborne exposure regime. Fish were sampled at days 0,
      4, and 10 for histology. All treatments caused organ injuries, and the kinds of
      pathologies observed with Cu-NPs were broadly of the same type as CuSO(4)
      including: hyperplasia, aneurisms, and necrosis in the secondary lamellae of the
      gills; swelling of goblet cells, necrosis in the mucosa layer and vacuole
      formation in the gut; hepatitis-like injury and cells with pyknotic nuclei in the
      liver; damage to the epithelium of some renal tubules and increased Bowman's
      space in the kidney. In the brain, some mild changes were observed in the nerve
      cell bodies in the telencephalon, alteration in the thickness of the
      mesencephalon layers, and enlargement of blood vessel on the ventral surface of
      the cerebellum. Changes in the proportional area of muscle fibres were observed
      in skeletal muscle. Overall the data showed that pathology from CuSO(4) and Cu
      NPs were of similar types, but there were some material-type effects in the
      severity or incidence of injuries with Cu-NPs causing more injury in the
      intestine, liver and brain than the equivalent concentration of CuSO(4) by the
      end of the experiment, but in the gill and muscle CuSO(4) caused more pathology.

PMID- 23174145
TI  - Assessment of the PROBIT approach for estimating the prevalence of global,
      moderate and severe acute malnutrition from population surveys.
AB  - OBJECTIVE: Prevalence of acute malnutrition is classically estimated by the
      proportion of children meeting a case definition in a representative population
      sample. In 1995 the WHO proposed the PROBIT method, based on converting
      parameters of a normally distributed variable to cumulative probability, as an
      alternative method requiring a smaller sample size. The present study compares
      classical and PROBIT methods for estimating the prevalence of global, moderate
      and severe acute malnutrition (GAM, MAM and SAM) defined by weight-for-height Z
      score (WHZ) or mid-upper arm circumference (MUAC). DESIGN: Bias and precision of
      classical and PROBIT methods were compared by simulating a total of 1.26 million
      surveys generated from 560 nutrition surveys. SETTING: Data used for simulation
      were derived from nutritional surveys of children aged 6-59 months carried out in
      thirty-one countries around the world. SUBJECTS: Data of 459 036 children aged 6
      59 months from representative samples were used to generate simulated
      populations. RESULTS: The PROBIT method provided an estimate of GAM, MAM and SAM
      using WHZ or MUAC proportional to the true prevalence with a small systematic
      overestimation. The PROBIT method was more precise than the classical method for
      estimating the prevalence for GAM, MAM and SAM by WHZ or MUAC for small sample
      sizes (i.e. n<150 for SAM and GAM; n<300 for MAM), but lost this advantage when
      sample sizes increased. CONCLUSIONS: The classical method is preferred for
      estimating acute malnutrition prevalence from large sample surveys. The PROBIT
      method may be useful in sentinel-site surveillance systems with small sample
      sizes.

PMID- 23174146
TI  - Pb2+ exposure induced microsatellite instability in Pisum sativum in a locus
      related with glutamine metabolism.
AB  - Lead (Pb) is a toxic element, but its putative mutagenic effects in plant cells,
      using molecular markers, remain to unveil. To evaluate if Pb induces
      mutagenicity, Pisum sativum L. seedlings were exposed to Pb(2+) (up to 2000 mg L(
      1)) for 28 days and the instability of microsatellites (or Simple Sequence
      Repeats, SSR) was analyzed in leaves and roots. The analysis of eight selected
      microsatellites (SSR1-SSR8) demonstrated that only at the highest dosage
      microsatellite instability (MSI) occurred, at a frequency of 4.2%. Changes were
      detected in one microsatellite (SSR6) that is inserted in the locus for glutamine
      synthetase. SSR6 products of roots exposed to the highest concentration of Pb
      were 3 bp larger than those of the control. Our data demonstrate that: (a) SSR
      technique is sensitive to detect Pb-induced mutagenicity in plants. MSI
      instability is Pb dose dependent and organ dependent (roots are more sensitive);
      (b) the Pb-sensitive SSR6 is inserted in the glutamine synthetase locus, with
      still unknown relation with functional changes of this enzyme; (c) Pb levels
      inducing MSI are much above the maximum admitted levels in some European Union
      countries for agricultural purpose waters. In conclusion, we propose here the
      potential use of SSR to evaluate Pb(2+)-induced mutagenicity, in combination with
      other genetic markers.

PMID- 23174147
TI  - Optimization of the medium composition of a biphasic production system for
      mycelial growth and spore production of Aschersonia placenta using response
      surface methodology.
AB  - The culture media for mycelial growth and sporulation of the entomopathogenic
      fungus Aschersonia placenta were optimized using the response surface method
      (RSM). Interactions of medium components and the optimization of a biphasic
      production system were studied using Box-Behnken design (BBD) with three levels
      of three variables. Experimentation confirmed that the model developed based on
      RSM and BBD successfully predicted mycelia production (R(2) = 0.9336) and conidia
      production (R(2) = 0.9532). In the first phase, mycelial dry weight was highest
      (2.14 +/- 0.17 g per 100ml of culture, mean+/-SE) when the concentrations (g/l)
      of glucose, vitamin B(6), and MgSO(4).7H(2)O were 31.4, 11.5, and 0.64,
      respectively. In the second phase, conidia production was highest (9.31 +/- 0.48
      * 10(7)sporespercm(2)) after 18d of cultivation in the medium containing 33.8 g/l
      of millet, 1.11 g/l of KH(2)PO(4), and 0.37 g/l of MgSO(4). Mycelial and conidial
      yields were 3.6- and 10-fold greater, respectively, with the optimized media than
      with the non-optimized basal media. The results indicate that RSM and BBD methods
      are effective for increasing the production of A. placenta mycelia and conidia.

PMID- 23174148
TI  - Umbilical cord diameter percentile curves and their correlation to birth weight
      and placental pathology.
AB  - OBJECTIVE: The aims of this study were to develop a nomogram of umbilical cord
      diameter (UCD) for pathologic examination of the placenta, to identify the
      umbilical cord components responsible for variations in UCD, and to examine the
      relationship between UCD and other placental pathologic features and perinatal
      outcome. STUDY DESIGN: We prospectively collected 497 umbilical cords between 18
      and 41 weeks' gestation over a 1-year period. Fresh-tissue UCD were grouped
      according to gestational age and compared to sonographic and histological
      measurements. Associations between UCD percentile and placental pathologic
      findings or obstetrical outcomes were examined. RESULTS: Mean UCD increased with
      gestational age until a plateau at 1.0 cm in the third trimester, a value that
      was 0.56 cm less than sonographic measurements prior to delivery and 0.17 cm
      greater than UCD measured histologically. Umbilical cord components varied with
      UCD percentile, with umbilical vessel area increased in thick cords (p < 0.001)
      and Wharton's jelly area reduced in thin cords (p = 0.002). Thin umbilical cords
      were associated with at least one pathologic histological placental finding (p =
      0.02), low placental weight (p < 0.001), single umbilical artery (p = 0.02),
      marginal cord insertion (p = 0.01), and low infant birth weight (p < 0.001).
      CONCLUSIONS: This study provides reference curves for post-delivery UCD from 18
      to 41 weeks' gestation for use by perinatal pathologists. We show that increased
      UCD is a function of increased umbilical blood vessel volume and decreased UCD is
      a function of decreased Wharton's jelly volume. UCD shows a strong association
      with placental and infant birth weight.

PMID- 23174149
TI  - Iodide transporters expression in early human invasive trophoblast.
AB  - CONTEXT: The placenta plays an essential role in the fetomaternal exchanges of
      iodine and thyroid hormones. Propylthiouracil (PTU) is presently considered to be
      the treatment of choice for hyperthyroidism during the first trimester of
      pregnancy. Little is known on the expression of iodide transporters in invasive
      human trophoblast and the possible effect of PTU on this early phase of human
      placental development. OBJECTIVE: To analyze during early pregnancy expression of
      sodium/iodide symporter (NIS) and pendrin at the feto-maternal interface in situ
      in first trimester placentas, in vitro during human trophoblastic cell
      differentiation in presence or not of PTU. DESIGN: NIS and pendrin
      immunodetection were performed on 8-10 WG placental tissue sections and in
      primary cultures of first trimester placenta trophoblastic cells, which
      differentiate in vitro into syncytiotrophoblast or invasive extravillous
      cytotrophoblasts (EVCT). The effect of PTU (1 mM) was tested in EVCT on iodide
      transporters expression, cell invasion, and hCG secretion. RESULTS: NIS and
      pendrin were present in early human trophoblast at the maternofetal interface.
      Their expression was modulated with in vitro trophoblast differentiation. Early
      invasive EVCT were characterized by higher expression of NIS than pendrin. In
      vitro PTU did modify significantly neither EVCT iodide transporters expression
      nor EVCT biological functions: i.e. invasive properties and hCG secretion.
      CONCLUSION: This study reveals that NIS is highly expressed in early human
      trophoblast at the feto-maternal interface. PTU has no effect on early human
      trophoblast invasion.

PMID- 23174150
TI  - The Birmingham Relationship Continuity Measure: the development and evaluation of
      a measure of the perceived continuity of spousal relationships in dementia.
AB  - BACKGROUND: Qualitative research has suggested that spousal carers of someone
      with dementia differ in terms of whether they perceive their relationship with
      that person as continuous with the premorbid relationship or as radically
      different, and that a perception of continuity may be associated with more person
      centered care and the experience of fewer of the negative emotions associated
      with caring. The aim of the study was to develop and evaluate a quantitative
      measure of the extent to which spousal carers perceive the relationship to be
      continuous. METHODS: An initial pool of 42 questionnaire items was generated on
      the basis of the qualitative research about relationship continuity. These were
      completed by 51 spousal carers and item analysis was used to reduce the pool to
      23 items. The retained items, comprising five subscales, were then administered
      to a second sample of 84 spousal carers, and the questionnaire's reliability,
      discriminative power, and validity were evaluated. RESULTS: The questionnaire
      showed good reliability: Cronbach's alpha for the full scale was 0.947, and test
      retest reliability was 0.932. Ferguson's delta was 0.987, indicating good
      discriminative power. Evidence of construct validity was provided by predicted
      patterns of subscale correlations with the Closeness and Conflict Scale and the
      Marwit-Meuser Caregiver Grief Inventory. CONCLUSION: Initial psychometric
      evaluation of the measure was encouraging. The measure provides a quantitative
      means of investigating ideas from qualitative research about the role of
      relationship continuity in influencing how spousal carers provide care and how
      they react emotionally to their caring role.

PMID- 23174151
TI  - Artificial fertilisation in a terrestrial toadlet (Pseudophryne guentheri):
      effect of medium osmolality, sperm concentration and gamete storage.
AB  - Anurans exhibit a greater reproductive diversity than any other vertebrate order.
      However, studies investigating the effects of the external fertilisation
      environment on fertilisation success are limited to aquatic-breeding species.
      This study investigated the effects of fertilisation medium osmolality, sperm
      concentration and short-term oocyte storage on fertilisation success in a
      terrestrial-breeding anuran, Pseudophryne guentheri. Split-clutch experimental
      designs were used to determine optimal fertilisation conditions. To determine the
      effect of short-term sperm storage, sperm viability was assessed using
      fluorescence microscopy and percentage sperm motility and velocity quantified
      with a computer-assisted sperm analysis system. Fertilisation success was highest
      in media ranging in osmolality from 25 mOsm kg-1 to 100 mOsm kg-1, representing a
      broader range and higher optimal osmolality than previously reported for aquatic
      breeders. High rates of fertilisation (>75%) were achieved in relatively low
      sperm concentrations (2.5*104 mL-1). Oocytes stored in isotonic solutions (200
      mOsm kg-1) retained fertilisation capacity (32%) after 8h of storage, while sperm
      suspensions maintained motility (>=26%) for 13 days. Additional studies on
      terrestrial-breeding anurans will be required to ascertain whether the optimal
      fertilisation conditions reported reflect adaptations to achieve fertilisation in
      a terrestrial environment.

PMID- 23174152
TI  - The history of neurosurgery in Anatolia and Turkey: the Turkish Neurosurgical
      Society.
AB  - Although the history of neurosurgery in Anatolia goes back ten thousand years,
      modern surgery began in Turkey in 1890. Neurosurgery in Turkey began in the first
      half of the 20th century. However, general surgeons began applying neurosurgical
      techniques back in the late 19th century. Most of these applications included
      procedures for craniocerebral traumas and infections. Dr. Cemil Topuzlu (1868
      1958) is the founder of modern surgery in Turkey. Dr. Abdulkadir Cahit Tuner
      became the first neurosurgeon with a degree in Turkey in 1923. The first
      neurosurgery department was established in Istanbul in 1923, and the first
      training program began in the late 1940s. Currently there are almost 1200
      neurosurgeons in Turkey and 75 training clinics at university hospitals and
      Training and Research Hospitals of the Ministry of Health provide neurosurgery
      training. The current state of neurosurgery in Turkey is parallel to that of the
      advanced Western countries. Apart from the application of neurosurgical
      procedures, there have been many scientific studies from Turkish neurosurgeons
      contributing to the total body of literature in neurosurgery.

PMID- 23174153
TI  - Atlantoaxial fusion: transarticular screws versus screw-rod constructs.

PMID- 23174154
TI  - Gallipoli: intercontinental leadership through the prism of Ataturk, Churchill,
      and Gandhi.

PMID- 23174155
TI  - Are we training too many neuroendovascular fellows?

PMID- 23174156
TI  - Iron--potential therapeutic target in hemorrhagic stroke.

PMID- 23174158
TI  - Why are GPs treating subclinical hypothyroidism? Case note review and GP survey.
AB  - BACKGROUND: Subclinical hypothyroidism (SCHo) is a common biochemical diagnosis
      in older age. Evidence of impact is inconclusive and guidelines are inconsistent.
      With increasing numbers of thyroid function tests (TFTs) performed, GPs
      frequently have to make management decisions regarding this diagnosis. However,
      little is known about how SCHo is currently being managed in primary care. AIM:
      To explore management of SCHo in primary care and GP reported rationale for
      treatment of SCHo in older individuals. DESIGN: Descriptive study using
      retrospective case note review and GP survey. SETTING: Nineteen General
      Practices, Central England, UK. METHODS: Follow-up of a large cohort with
      subsequent detailed review of individuals for whom therapy had been initiated
      following diagnosis of SCHo. Data on practice policies, and rationale behind
      treatment were collected via GP questionnaire. RESULTS: Forty-two individuals
      were treated following identification of SCHo. Factors regarded as supporting
      instigation of therapy recorded by practitioners included symptoms, a positive
      antithyroid antibody test and history of radioiodine therapy. In all, 55% were
      registered at 3/19 practices suggesting significant between practice variation.
      Reasons for testing included chronic disease check-up (n = 14), presenting
      'thyroid symptoms' (n = 5) and presenting other symptoms (n = 9). Reasons for
      therapy initiation were only recorded in 26 cases and included presence of
      symptoms, persistently high or increasing serum thyroid stimulating hormone
      concentration and patient request. Only 2/15 GPs reported having practice
      guidelines on management. CONCLUSION: Results suggest that GPs are uncertain how
      to interpret symptoms and TFT results in older individuals. There is considerable
      variation in management of SCHo between GPs with some GPs treating patients
      outside of all guideline recommendations.

PMID- 23174159
TI  - Immunoreactivity characterisation of the three structural regions of the human
      coronavirus OC43 nucleocapsid protein by Western blot: implications for the
      diagnosis of coronavirus infection.
AB  - Previous studies have reported that a prokaryotic-expressed recombinant
      nucleocapsid protein (NP) is a suitable reagent for the epidemiological screening
      of coronavirus infection. In this study, soluble recombinant human coronavirus
      OC43 (HCoV-OC43) NP was produced to examine the antigenicity of the HCoV-OC43 NP
      of betacoronavirus. Using the purified recombinant NP as an antigen, a polyclonal
      antibody from rabbit serum with specificity for HCoV-OC43 NP was generated; this
      antibody reacts specifically with HCoV-OC43 NP and does not cross-react with
      other human CoV NPs (including those of SARS-CoV and HCoV-229E) by Western blot.
      Sera from 26 young adults, 17 middle-aged and elderly patients with respiratory
      infection, and 15 cord blood samples were also tested. Strong reactivity to the
      NPs of HCoV-OC43 was observed in 96%, 82%, and 93% of the serum samples from the
      young adults, respiratory patients, and cord blood samples, respectively. To
      identify the immunoreactivities of the three structural regions of the NP that
      are recognised by the rabbit polyclonal antibody and human serum, the
      antigenicities of three protein fragments, including the N-terminal domain (aa 1
      173), the central-linker region (aa 174-300), and the C-terminal domain (aa 301
      448), were evaluated by Western blot. The rabbit polyclonal antibody demonstrated
      greater immunoreactivity to the central-linker region and the C-terminal domain
      than to the N-terminal domain. Three different patterns for the
      immunoreactivities of the three structural regions of HCoV-OC43 NP were observed
      in human serum, suggesting variability in the immune responses that occur during
      HCoV-OC43 infection in humans. The central-linker region of the NP appeared to be
      the most highly immunoreactive region for all three patterns observed. The goal
      of this study was to offer insight into the design of diagnostic tools for HCoV
      infection.

PMID- 23174157
TI  - How to deal with dialysis catheters in the ICU setting.
AB  - Acute kidney insufficiency (AKI) occurs frequently in intensive care units
      (ICU). In the management of vascular access for renal replacement therapy (RRT),
      several factors need to be taken into consideration to achieve an optimal RRT
      dose and to limit complications. In the medium and long term, some individuals
      may become chronic dialysis patients and so preserving the vascular network is of
      major importance. Few studies have focused on the use of dialysis catheters (DC)
      in ICUs, and clinical practice is driven by the knowledge and management of long
      term dialysis catheter in chronic dialysis patients and of central venous
      catheter in ICU patients. This review describes the appropriate use and
      management of DCs required to obtain an accurate RRT dose and to reduce
      mechanical and infectious complications in the ICU setting. To deliver the best
      RRT dose, the length and diameter of the catheter need to be sufficient. In
      patients on intermittent hemodialysis, the right internal jugular insertion is
      associated with a higher delivered dialysis dose if the prescribed extracorporeal
      blood flow is higher than 200 ml/min. To prevent DC colonization, the physician
      has to be vigilant for the jugular position when BMI < 24 and the femoral
      position when BMI > 28. Subclavian sites should be excluded. Ultrasound guidance
      should be used especially in jugular sites. Antibiotic-impregnated dialysis
      catheters and antibiotic locks are not recommended in routine practice. The
      efficacy of ethanol and citrate locks has yet to be demonstrated. Hygiene
      procedures must be respected during DC insertion and manipulation.

PMID- 23174160
TI  - A single-tube duplex and multiplex PCR for simultaneous detection of four cassava
      mosaic begomovirus species in cassava plants.
AB  - A single-tube duplex and multiplex PCR was developed for the simultaneous
      detection of African cassava mosaic virus (ACMV), East African cassava mosaic
      Cameroon virus (EACMCV), East African cassava mosaic Malawi virus (EACMMV) and
      East African cassava mosaic Zanzibar virus (EACMZV), four cassava mosaic
      begomoviruses (CMBs) affecting cassava in sub-Saharan Africa. Co-occurrence of
      the CMBs in cassava synergistically enhances disease symptoms and complicates
      their detection and diagnostics. Four primer pairs were designed to target DNA-A
      component sequences of cassava begomoviruses in a single tube PCR amplification
      using DNA extracted from dry-stored cassava leaves. Duplex and multiplex PCR
      enabled the simultaneous detection and differentiation of the four CMBs, namely
      ACMV (940bp), EACMCV (435bp), EACMMV (504bp) and EACMZV (260bp) in single and
      mixed infections, and sequencing results confirmed virus identities according to
      the respective published sequences of begomovirus species. In addition, we report
      here a modified Dellapotra et al. (1983) protocol, which was used to extract DNA
      from dry and fresh cassava leaves with comparable results. Using the duplex and
      multiplex techniques, time was saved and amount of reagents used were reduced,
      which translated into reduced cost of the diagnostics. This tool can be used by
      cassava breeders screening for disease resistance; scientists doing virus
      diagnostic studies; phytosanitary officers checking movement of diseased planting
      materials, and seed certification and multipliers for virus indexing.

PMID- 23174162
TI  - Analysis of koi herpesvirus latency in wild common carp and ornamental koi in
      Oregon, USA.
AB  - Koi herpesvirus (KHV) infection is associated with high mortalities in both
      common carp (Cyprinus carpio carpio) and koi carp (Cyprinus carpio koi)
      worldwide. Although acute infection has been reported in both domestic and wild
      common carp, the status of KHV latent infection is largely unknown in wild common
      carp. To investigate whether KHV latency is present in wild common carp, the
      distribution of KHV latent infection was investigated in two geographically
      distinct populations of wild common carp in Oregon, as well as in koi from an
      Oregon-based commercial supplier. Latent KHV infection was demonstrated in white
      blood cells from each of these populations. Although KHV isolated from acute
      infections has two distinct genetic groups, Asian and European, KHV detected in
      wild carp has not been genetically characterized. DNA sequences from ORF 25 to 26
      that are unique between Asian and European were investigated in this study. KHV
      from captive koi and some wild common carp were found to have ORF-25-26 sequences
      similar to KHV-J (Asian), while the majority of KHV DNA detected in wild common
      carp has similarity to KHV-U/-I (European). In addition, DNA sequences from IL
      10, and TNFR were sequenced and compared with no differences found, which
      suggests immune suppressor genes of KHV are conserved between KHV in wild common
      carp and koi, and is consistent with KHV-U, -I, -J.

PMID- 23174161
TI  - Efficient production of foot-and-mouth disease virus empty capsids in insect
      cells following down regulation of 3C protease activity.
AB  - Foot-and-mouth disease virus (FMDV) is a significant economically and distributed
      globally pathogen of Artiodactyla. Current vaccines are chemically inactivated
      whole virus particles that require large-scale virus growth in strict bio
      containment with the associated risks of accidental release or incomplete
      inactivation. Non-infectious empty capsids are structural mimics of authentic
      particles with no associated risk and constitute an alternate vaccine candidate.
      Capsids self-assemble from the processed virus structural proteins, VP0, VP3 and
      VP1, which are released from the structural protein precursor P1-2A by the action
      of the virus-encoded 3C protease. To date recombinant empty capsid assembly has
      been limited by poor expression levels, restricting the development of empty
      capsids as a viable vaccine. Here expression of the FMDV structural protein
      precursor P1-2A in insect cells is shown to be efficient but linkage of the
      cognate 3C protease to the C-terminus reduces expression significantly.
      Inactivation of the 3C enzyme in a P1-2A-3C cassette allows expression and
      intermediate levels of 3C activity resulted in efficient processing of the P1-2A
      precursor into the structural proteins which assembled into empty capsids.
      Expression was independent of the insect host cell background and leads to
      capsids that are recognised as authentic by a range of anti-FMDV bovine sera
      suggesting their feasibility as an alternate vaccine.

PMID- 23174163
TI  - Monoclonal antibody-based ELISA for detection of antibodies against H5 avian
      influenza viruses.
AB  - Diagnostic and containment measures are essential for the management of avian
      influenza. In this study, a monoclonal antibody (MAb)-based competitive ELISA for
      detecting antibodies against H5 avian influenza viruses was developed and
      validated. Twenty-five anti-H5 MAbs were characterised using competitive,
      indirect and sandwich ELISAs, immunofluorescence, Western blotting and virus
      neutralisation and haemagglutination inhibition assays. One MAb (5D8) with wide
      intra-subtype cross-reactivity was selected and characterised using escape mutant
      selection. Epitope analysis showed that this MAb recognises a conformational
      epitope comprising amino acid residues in positions 170, 235 and 240 located in
      the receptor binding domain. The diagnostic performance of the test was evaluated
      by ROC analysis using a panel of 950 known sera collected from different avian
      species, including chickens, turkeys, ducks, pheasants, wild Anseriformes and
      ostriches. The competitive ELISA had excellent diagnostic performance and
      discriminatory power with high Se and Sp values (Se: 99.6-95% CI 98.0-100; Sp:
      99.4-95% CI 98.5-99.8). In addition to its excellent diagnostic performance,
      properties of the competitive ELISA, such as high feasibility of testing sera
      without pre-treatment and potential for automation and instrument-mediated
      detection, make it ideal for screening samples, confirming positive HI assay
      results or analysing samples that are difficult to test using the HI assay.

PMID- 23174164
TI  - Validation of a commercial real-time PCR kit for specific and sensitive detection
      of Pseudorabies.
AB  - Pseudorabies virus is the causative agent of Aujeszky's disease, one of the OIE
      listed diseases that mainly affects swine, but also can affect other animal
      species, and which can lead to heavy economic losses in pig industry. This study
      was designed to evaluate the performance of the ADIAVET((r)) PRV REALTIME kit, a
      new commercial real time PCR kit for Pseudorabies virus genome detection
      developed by the French manufacturer Adiagene. It can be used on pig biological
      samples such as nasal swab supernatant, tonsil, brain or lung samples, or on
      samples from other susceptible animals, such as domestic carnivores. This ready
      to-use duplex PCR assay contains an external positive control, appropriate for
      assessing DNA extraction efficiency and the presence of PCR inhibitors. The
      analytical specificity and sensitivity, intra- and inter-assay repeatability and
      diagnostic characteristics of the kit were determined and compared with virus
      isolation, which is the gold standard. Based on these results, the ADIAVET((r))
      PRV REALTIME kit received full validation for diagnostic purposes.

PMID- 23174165
TI  - Rapid detection and typing of Molluscum contagiosum virus by FRET-based real-time
      PCR.
AB  - A fluorescence resonance energy transfer (FRET)-based real-time PCR (RT-PCR) was
      developed for very sensitive and specific detection of Molluscum contagiosum
      virus (MCV), as well as reliable differentiation of the two MCV subtype genetic
      lineages, MCV1 and MCV2, in a single reaction. The assay employs modified primers
      specific for the viral MC021L gene and uses two novel FRET hybridization probes
      to detect polymorphisms specific for each of the two subtypes. The sensitivity of
      the assay at a 95% detection level for both MCV subtypes was 3.3 DNA
      copies/reaction and the dynamic range was nine orders of magnitude,
      discriminating 10-10(9) viral genome equivalents/reaction. Post-amplification
      probe-specific dissociation analysis differentiated the two viral subtypes
      reliably in all tested concentrations. Testing of 43 tissue specimens clinically
      diagnosed as MCV lesions showed complete agreement with the results obtained with
      previously described MCV specific MC080R Taqman RT-PCR and MC021L whole gene
      sequencing. The novel assay is simple, robust and easy to perform, and may be of
      great value for clinical and epidemiological studies of MCV infections and
      related conditions.

PMID- 23174166
TI  - Electrophysiological characterization of scars detected by contrast enhanced
      magnetic resonance imaging in patients with non-ischemic cardiomyopathy.

PMID- 23174167
TI  - Drug adherence and the incidence of coronary heart disease- and stroke-specific
      mortality among 218,047 patients newly prescribed an antihypertensive medication:
      a five-year cohort study.
AB  - BACKGROUND: Randomized trials have shown that optimal adherence to
      antihypertensive agents could protect against cardiovascular diseases, but
      whether adherence reduces cardiovascular deaths in community settings has not
      been explored so fully. This study evaluates the association between
      antihypertensive adherence and cardiovascular (coronary heart disease and stroke)
      mortality in the primary care settings. METHODS: From a territory-wide database
      in Hong Kong, we included all patients who were prescribed their first-ever
      antihypertensive agents in the years between 2001 and 2005 from the public
      healthcare sector. All patients were followed up for five years, and assigned as
      having poor (Proportion of Days Covered [PDC]<40%), intermediate (40-79%), and
      high (>= 80%) adherence to antihypertensive agents. The association between
      antihypertensive adherence and cardiovascular mortality was evaluated by using
      the Cox proportional hazard models. RESULTS: From a total of 218,047 eligible
      patients, 3825 patients (1.75%) died of cardiovascular disease within five years
      after having received their first-ever antihypertensive agents. The proportions
      of patients having poor, intermediate, and high medication adherence were 32.9%,
      12.1%, and 55.0%, respectively. Higher adherence levels at PDC 40%-79% (HR=0.46,
      95% C.I. 0.41-0.52, p<0.001) and >= 80% (HR=0.91, 95% C.I. 0.85-0.98, p=0.012)
      were significantly less likely to be associated with mortality than the poor
      adherence (PDC0.040) group. CONCLUSIONS: Better antihypertensive adherence was
      associated with lower cardiovascular mortality. This highlights the need to
      promote adherence through strategies which have been proved to be effective in
      clinical settings.

PMID- 23174168
TI  - Hast thou slain the Jabberwock of funnel plot asymmetry? From the meta-analysis
      of smoking bans for reduction of acute myocardial infarction.

PMID- 23174169
TI  - Highlights of the mechanistic and therapeutic cachexia and sarcopenia research
      2010 to 2012 and their relevance for cardiology.
AB  - Sarcopenia and cachexia are significant medical problems with a high disease
      related burden in cardiovascular illness. Muscle wasting and weight loss are very
      frequent particularly in chronic heart failure and they relate to poor prognosis.
      Although clinically largely underestimated, the fields of cachexia and sarcopenia
      are of great relevance to cardiologists. In cachexia and sarcopenia a significant
      number of research publications related to basic science questions of muscle
      wasting and lipolysis were published between 2010 and 2012. Recently, the two
      processes of muscle wasting and lipolysis were found to be closely linked.
      Treatment research in pre-clinical models involves studies on a number of
      different therapeutic entities, including ghrelin, selective androgen receptor
      modulators (SARMs), as well as drugs targeting myostatin or melanocortin-4. In
      the human setting, studies using enobosarm (a SARM) and anamorelin (ghrelin) are
      in phase III. The last 3 years has seen significant efforts to define the field
      using consensus statements. In the future, these definitions should also be
      considered for guidelines and treatment trials in cardiovascular medicine. The
      current review aims to summarize important information and development in the
      fields of muscle wasting, sarcopenia and cachexia focussing on findings in
      cardiovascular research, in order for cardiologists to have a better
      understanding of the progress in the still not well enough known field.

PMID- 23174170
TI  - Contrasting effects of diabetes and metabolic syndrome on post-operative atrial
      fibrillation and in-hospital outcome after cardiac surgery.

PMID- 23174171
TI  - The Last Judgment upon abdominal aortic aneurysm screening.

PMID- 23174172
TI  - TAPSE should be a routine clinical tool in assessing congenital heart diseases
      with right ventricular involvement.

PMID- 23174173
TI  - Cardiotoxicity of a non-pegylated liposomal doxorubicin-based regimen versus an
      epirubicin-based regimen for breast cancer: the LITE (Liposomal doxorubicin
      Investigational chemotherapy-Tissue Doppler imaging Evaluation) randomized pilot
      study.

PMID- 23174174
TI  - Congestive heart failure as cause of death in an anorexia nervosa fatal case.

PMID- 23174175
TI  - A 64,489-patient full-disclosure database of cardiovascular risk factors and
      events status analysed in a Bayesian framework: a unique contribution to
      predictive science.
AB  - Today in the International Journal of Cardiology Liu et al. [1] publish an
      unusual exercise in open science which should set a pioneering trend for future
      knowledge sharing. They present both the principle and a large fully-analysed
      real world dataset to show how Bayesian reasoning can be practically helpful for
      clinicians at the front line. The Bayesian approach differs from the frequentist
      approach that is more commonly seen in reports of clinical research. Instead of a
      probability having a single point estimate and confidence interval, it instead
      has a complete probability density function. For Bayesian analysis in general,
      instead of there being no information before a particular study, there is some
      information--the "prior". The difference is that while the frequentist approach
      assumes that before the study all probabilities are equally plausible, the
      Bayesian approach recognises that even before the study, some probabilities are
      more likely than others. Therefore, after the study, the Bayesian approach
      produces a new distribution of the probability--the "posterior"--which
      incorporates both the raw study results and the prior distribution. Bayesian
      approaches are routinely used in medical decision-making and everyday life,
      perhaps without even realising it. Clinical test results are rarely interpreted
      in isolation. Instead, the background clinical belief of plausibility of various
      diagnoses (the prior) is updated in light of test results, to form a new set of
      beliefs (the posterior). We more readily accept assertions that are within the
      range of our prior beliefs than those that substantially contradict those
      beliefs. To build a model of cardiovascular risk, the Bayesian approach begins
      with an assumed distribution for the risk depending on the risk factors and
      progressively updates it with the experience of patients and their outcomes. Each
      additional patient makes a contribution to the model's knowledge. Then the model
      can be applied to any individual, and provide a distribution for the risk of that
      individual. This might be narrow, indicating precise risk evaluation or wide,
      indicating substantial persisting uncertainty. The authors' openness to share the
      whole dataset creates three exciting avenues for advancement in the field. First,
      researchers could analyse the dataset in different ways, for example, by
      proposing distributions other than the normal. Second, they could use the outcome
      of this dataset as a starting point for further upgrading the model with future
      data. Third, researchers are absolutely free to use this data to explore other
      interrelationships between the variables for new purposes. For example, we have
      studied the joint distribution of two variables that have a multiplicative effect
      of cardiovascular risk: cholesterol and blood pressure. The online supplement to
      this editorial contains the raw dataset in .zip format to facilitate its download
      for the reader. Freely exposing all the data is currently remarkable but on
      objective reflection, it is hard to understand why it is not already a normal
      practice. Do authors fear that readers despite a handicap of years might trump
      them to future findings? Or do they have something to hide? We do not know but
      this paper is changing our practice and we hope it will change yours.

PMID- 23174176
TI  - Treatment of stage I lung cancer in high-risk and inoperable patients: comparison
      of prospective clinical trials using stereotactic body radiotherapy (RTOG 0236),
      sublobar resection (ACOSOG Z4032), and radiofrequency ablation (ACOSOG Z4033).
AB  - OBJECTIVE: The purpose of the present study was to compare the selection criteria
      and short-term outcomes among 3 prospective clinical trials using stereotactic
      body radiotherapy (Radiation Therapy Oncology Group [RTOG] trial 0236), sublobar
      resection (American College of Surgeons Oncology Group [ACOSOG] trial Z4032), and
      radiofrequency ablation (ACOSOG trial Z4033). METHODS: The selection criteria and
      outcomes were compared among RTOG 0236 (n = 55), ACOSOG Z4032 (n = 211), and
      ACOSOG Z4033 (n = 51). Age, Eastern Cooperative Oncology Group performance
      status, percentage of predicted forced expiratory volume in 1 second, and
      percentage of predicted carbon monoxide diffusing capacity of the lung were used
      to perform a propensity-matched analysis among patients with clinical stage 1A in
      RTOG 0236 and ACOSOG Z4032. RESULTS: The patients in ACOSOG Z4033 undergoing
      radiofrequency ablation were older (75.6 +/- 7.5 years) than those in RTOG 0236
      (72.5 +/- 8.8 years) and ACOSOG Z4032 (70.2 +/- 8.5 years; P = .0003). The
      pretreatment percentage of predicted forced expiratory volume in 1 second was
      61.3% +/- 33.4% for RTOG 0236, 53.8% +/- 19.6% for ACOSOG Z4032, and 48.8% +/-
      20.3% for ACOSOG Z4033 (P = .15). The pretreatment percentage of predicted carbon
      monoxide diffusing capacity of the lung was 61.6% +/- 30.2% for RTOG 0236, 46.4%
      +/- 15.6% for ACOSOG Z4032, and 43.7% +/- 18.0% for ACOSOG Z4033 (P = .001). The
      overall 90-day mortality for stereotactic body radiotherapy, surgery, and
      radiofrequency ablation was 0%, 2.4% (5/211), and 2.0% (1/51), respectively (P =
      .5). Overall, the unadjusted 30-day grade 3+ adverse events were more common with
      surgery than with stereotactic body radiotherapy (28% vs 9.1%, P = .004),
      although no difference was between the 2 groups at 90 days. Among the patients
      with clinical stage IA in ACOSOG Z4032, 29.3% had a more advanced pathologic
      stage at surgery. A propensity-matched comparison showed no difference between
      stereotactic body radiotherapy and surgery for 30-day grade 3+ adverse events
      (odds ratio, 2.37; 95% confidence interval, 0.75-9.90; P = .18). CONCLUSIONS:
      Among appropriately matched patients, no difference was seen in early morbidity
      between sublobar resection and stereotactic body radiotherapy. These results
      underscore the need for a randomized trial to delineate the relative survival
      benefit of each modality and to help stratify patients considered high risk.

PMID- 23174177
TI  - Intraoperative hyperthermic chemotherapy perfusion for malignant pleural
      mesothelioma: an in vitro evaluation.
AB  - OBJECTIVES: Hyperthermic chemotherapy perfusion has been used in the treatment of
      both pleural and peritoneal mesothelioma without an extensive basic science
      foundation. Clinical data are limited with no prospective randomized trials to
      support the use of this potentially toxic therapy. We sought to generate basic
      scientific support for this clinical practice and to define the optimal
      conditions for use in future clinical trials. METHODS: Growth of a variety of in
      vitro established cell lines, including a hyperthermia-sensitive Chinese hamster
      ovary (CHO)-K1 cell line, a normal lung fibroblast line (MRC-5), a lung cancer
      line (A549), and 3 human mesothelioma cell lines (NCI-H28, NCI-H2052, and MSTO
      211H), was assessed using a novel tetrazolium compound (3-(4,5-dimethylthiazol-2
      yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt
      [MTS]) and an electron coupling reagent (phenazine methosulfate), which measures
      the absorbance at 490 nm of a formazan product reduced from MTS by living cells
      (MTS metabolic assay), or a standard dilution clonogenic assay, which enumerates
      colony-forming units of more than 50 cells. Each cell line was plated into flasks
      and then exposed to varying combinations of chemotherapy agents and hyperthermia
      (37 degrees C-45 degrees C). The cells then were harvested and assessed in either
      assay. The role of chemotherapeutic agents currently most commonly used in
      clinical practice, including cisplatin, gemcitabine, and pemetrexed, was assessed
      with and without simultaneous heat exposure. RESULTS: Conditions initially were
      explored using hyperthermia alone in CHO-K1, A549, and NCI-H28 cell lines using
      temperatures of 37 degrees C, 42 degrees C, and 45 degrees C for 20, 40, and 60
      minutes, respectively. This showed a reproducible dose-response curve in CHO-K1
      cells with increasing temperature producing lower survival to only 1.5% of the
      control at 45 degrees C for 60 minutes (P < .01). The A549 cells also showed a
      response but only at the highest temperature, and the NCI-H28 cells showed a more
      modest reduction to 65% at 45 degrees C for 60 minutes (P < .01). When the 2
      assays were directly compared, the MTS assay failed to detect differences between
      groups and therefore was discontinued from the remainder of these experiments.
      Next, hyperthermia was limited to the physiologic limit of 42 degrees C, and the
      addition of chemotherapy was assessed. Doses were chosen on the basis of prior
      pharmacokinetic data from studies showing a maximum tissue/blood level of 200
      ng/mL for cisplatin pleural instillation and were thought to more accurately
      reflect actual tumor levels. Cisplatin alone modestly reduced the clonogenic
      potential to 26%, 16.4%, and 13.6% at 42 degrees C, respectively, for 60 minutes
      (P < .01); however, this was only a further reduction of 29.6%, 33.8%, and 34.2%,
      respectively, from the cisplatin alone control. Therefore, most of the reduction
      was attributable to chemotherapy and not hyperthermia. With combinations of
      cisplatin/gemcitabine and cisplatin/pemetrexed, the effect was larger, with
      reduction to 9.6%, 0%, and 0%, respectively (P < .01) (incremental reduction of
      16.5%, 0%, and 0%, respectively, due to hyperthermia). Cisplatin/pemetrexed
      produced essentially identical results. CONCLUSIONS: Intrapleural chemotherapy
      seems to be most effective when using 2 drug combinations. All mesothelioma cell
      lines showed no particular sensitivity to heat. The use of hyperthermia alone or
      with chemotherapy produces at best only a modest effect and does not necessarily
      support its current clinical use.

PMID- 23174178
TI  - Activation of JAK-STAT3 signaling pathway in chronic subdural hematoma outer
      membranes.
AB  - Chronic subdural hematoma (CSDH) is an inflammatory disease, the mechanism of
      which still remains to be elucidated. Interleukin-6 (IL-6), one of the
      inflammatory cytokines regulating janus kinase (JAK)-signal transducer and
      activator of transcription (STAT) signaling pathway, is expressed in human CSDH
      fluid. The status of this signaling pathway in human CSDH outer membranes was
      examined in the present study using outer membranes obtained during trepanation
      surgery. Concentrations of IL-6 in human CSDH fluids were measured using an
      enzyme immuno-assay kit. Expression patterns of JAK1, STAT1, phosphorylated (p)
      STAT1 at Tyr(701) and at Ser(727), STAT3, p-STAT3 at Tyr(705) and at Ser(727) and
      actin in outer membranes were examined by Western blot analysis and
      immunohistochemistry. IL-6 is significantly expressed in human CSDH fluids
      compared with control cerebrospinal fluid. JAK1, STAT1 and STAT3 were detected in
      all cases. The expression of p-STAT3 at Tyr(705) is more significant compared
      with that of p-STAT1 at Tyr(701). In some cases, p-STAT3 at Ser(727) could also
      be detected, while p-STAT1 at Ser(727) could not. The localizations of STAT1 and
      STAT3 were revealed to be present in fibroblasts in human CSDH outer membranes,
      especially when p-STAT3 at Tyr(705) was in the nuclei of fibroblasts. These
      findings suggest that JAK1-STAT3 signaling is dominantly activated in fibroblasts
      of human CSDH outer membranes compared with STAT1 and indicate the possibility
      that this JAK1-STAT3 pathway might be activated by IL-6 and play a critical role
      in progression of human CSDH.

PMID- 23174179
TI  - Upregulation of reggie-1/flotillin-2 promotes axon regeneration in the rat optic
      nerve in vivo and neurite growth in vitro.
AB  - The ability of fish retinal ganglion cells (RGCs) to regenerate their axons was
      shown to require the re-expression and function of the two proteins reggie-1 and 
      2. RGCs in mammals fail to upregulate reggie expression and to regenerate axons
      after lesion suggesting the possibility that induced upregulation might promote
      regeneration. In the present study, RGCs in adult rats were induced to express
      reggie-1 by intravitreal injection of adeno-associated viral vectors (AAV2/1)
      expressing reggie-1 (AAV.R1-EGFP) 14d prior to optic nerve crush. Four weeks
      later, GAP-43-positive regenerating axons had crossed the lesion and grown into
      the nerve at significantly higher numbers and length (up to 5mm) than the control
      transduced with AAV.EGFP. Consistently, after transduction with AAV.R1-EGFP as
      opposed to AAV.EGFP, primary RGCs in vitro grew long axons on chondroitin sulfate
      proteoglycan (CSPG) and Nogo-A, both glial cell-derived inhibitors of neurite
      growth, suggesting that reggie-1 can provide neurons with the ability to override
      inhibitors of neurite growth. This reggie-1-mediated enhancement of growth was
      reproduced in mouse hippocampal and N2a neurons which generated axons 40-60%
      longer than their control counterparts. This correlates with the reggie-1
      dependent activation of Src and PI3 kinase (PI3K), of the Rho family GTPase Rac1
      and downstream effectors such as cofilin. This increased growth also depends on
      TC10, the GTPase involved in cargo delivery to the growth cone. Thus, the
      upregulation of reggie-1 in mammalian neurons provides nerve cells with neuron
      intrinsic properties required for axon growth and successful regeneration in the
      adult mammalian CNS.

PMID- 23174180
TI  - AT2-receptor stimulation enhances axonal plasticity after spinal cord injury by
      upregulating BDNF expression.
AB  - It is widely accepted that the angiotensin AT2-receptor (AT2R) has
      neuroprotective features. In the present study we tested pharmacological AT2R
      stimulation as a therapeutic approach in a model of spinal cord compression
      injury (SCI) in mice using the novel non-peptide AT2R-agonist, Compound 21 (C21).
      Complementary experiments in primary neurons and organotypic cultures served to
      identify underlying mechanisms. Functional recovery and plasticity of
      corticospinal tract (CST) fibers following SCI were monitored after application
      of C21 (0.3mg/kg/dayi.p.) or vehicle for 4 weeks. Organotypic co-culture of GFP
      positive entorhinal cortices with hippocampal target tissue served to evaluate
      the impact of C21 on reinnervation. Neuronal differentiation, apoptosis and
      expression of neurotrophins were investigated in primary murine astrocytes and
      neuronal cells. C21 significantly improved functional recovery after SCI compared
      to controls, and this significantly correlated with the increased number of CST
      fibers caudal to the lesion site. In vitro, C21 significantly promoted
      reinnervation in organotypic brain slice co-cultures (+50%) and neurite outgrowth
      of primary neurons (+25%). C21-induced neurite outgrowth was absent in neurons
      derived from AT2R-KO mice. In primary neurons, treatment with C21 further induced
      RNA expression of anti-apoptotic Bcl-2 (+75.7%), brain-derived neurotrophic
      factor (BDNF) (+53.7%), the neurotrophin receptors TrkA (+57.4%) and TrkB
      (+67.9%) and a marker for neurite growth, GAP43 (+103%), but not TrkC. Our data
      suggest that selective AT2R-stimulation improves functional recovery in
      experimental spinal cord injury through promotion of axonal plasticity and
      through neuroprotective and anti-apoptotic mechanisms. Thus, AT2R-stimulation may
      be considered for the development of a novel therapeutic approach for the
      treatment of spinal cord injury.

PMID- 23174181
TI  - Relation of severe deficiency of vitamin D to cardiovascular mortality during
      acute coronary syndromes.
AB  - Vitamin D deficiency is associated with risk for a first cardiovascular event in
      the general population, possibly because of inflammation, insulin resistance, and
      neurohumoral activation. However, its relation with outcomes in acute coronary
      syndromes has not been reported. To test the hypothesis that severe deficiency of
      vitamin D is independently associated with cardiovascular mortality during ACS,
      206 patients admitted for unstable angina, non-ST-segment elevation myocardial
      infarction, or ST-segment elevation acute myocardial infarction had 25
      hydroxyvitamin D serum levels measured at admission. Severe vitamin D deficiency
      was defined a priori as a value <=10 ng/ml. The average concentration of vitamin
      D was 20 +/- 8.2 ng/ml, and 10% of patients were severely deficient (95%
      confidence interval 6.6% to 15%). Cardiovascular mortality during hospitalization
      took place in 14 patients, an incidence of 6.8%. Patients with severe vitamin D
      deficiency had in-hospital cardiovascular mortality of 24%, significantly higher
      than the 4.9% observed in the remaining patients (relative risk 4.3, 95%
      confidence interval 1.8 to 10, p = 0.001). After adjustment for Global Registry
      of Acute Coronary Events (GRACE) score, Gensini angiographic score, and potential
      confounding variables, severe deficiency of vitamin D remained an independent
      predictor of in-hospital cardiovascular mortality (odds ratio 14, 95% confidence
      interval 1.2 to 158, p = 0.03). In conclusion, severe vitamin D deficiency is
      independently associated with in-hospital cardiovascular mortality in patients
      with acute coronary syndromes.

PMID- 23174182
TI  - Pregnancy outcomes in women with aortic valve substitutes.
AB  - Young women who require aortic valve replacement need information on the
      potential cardiac and obstetric complications of pregnancy for the different
      valve substitutes available. We, therefore, assessed the pregnancy outcomes in
      women who had received an autograft, homograft, or mechanical valve in the aortic
      position. Women who were pregnant after surviving aortic valve replacement at our
      institution from 1987 to 2011 were included. Information on cardiac status and
      pregnancy outcome was obtained through the hospital medical records and by an
      extensive patient questionnaire. A total of 40 women experienced 67 pregnancies,
      of which 55 (82%) were completed pregnancies, 6 (9%) were miscarriages, and 6
      (9%) were terminated. Of the 40 women, 18 (45%) had a pulmonary autograft, 13
      (32%) a homograft, and 9 (23%) a mechanical valve. The mean age at the first
      pregnancy was 30.0 +/- 5.7 years. No maternal mortality but 1 fetal death (1.8%)
      and 1 neonatal death (1.8%) occurred. Maternal cardiac complications developed in
      13% and obstetric complications in 38% of the completed pregnancies. Heart
      failure (9%), arrhythmias (7%), hypertension-related disorders (7%), preterm
      delivery (24%), and small-for-gestational-age infants (15%) were most often
      encountered. Mechanical valve recipients had the greatest incidence of both
      cardiac and obstetric complications. In conclusion, pregnancy-associated
      complications after aortic valve replacement were common, and human tissue valves
      should be considered in the discussion for the optimal aortic valve substitute in
      a young woman. However, careful obstetric monitoring is mandatory.

PMID- 23174183
TI  - Utility of high-sensitivity C-reactive protein versus coronary artery calcium for
      the detection of obstructive stenoses in stable patients.
AB  - The inflammatory biomarker high-sensitivity C-reactive protein (hs-CRP) has
      emerged as a predictor of future cardiovascular events. Screening for coronary
      artery calcium (CAC) is an alternative method for stratifying subjects by their
      cardiovascular risk. It is unclear, however, how hs-CRP compares with CAC scoring
      for the detection of obstructive coronary artery stenoses. We, thus, evaluated
      the association, if any, between hs-CRP and CAC scores for the detection of
      obstructive stenoses in a low-risk population with well-controlled traditional
      cardiovascular risk factors. In the present study of 1,079 stable subjects, 38
      (3.5%) severely obstructive stenoses were found initially by coronary computed
      tomographic angiography and confirmed subsequently using invasive coronary
      angiography. The univariate predictors of severely obstructive coronary artery
      disease included the use of antihypertensive agents (p = 0.03), angina (p
      <0.001), and an elevated CAC score (p <0.001). The biomarker hs-CRP was not
      significantly associated with the presence of a severely obstructive stenosis. As
      the CAC scores increased, the frequency of obstructive stenosis also increased (p
      for trend <0.001). In contrast, the frequency of obstructive stenoses was low
      when CAC was not detected. This relation remained significant after adjustment
      for antihypertensive medication use and angina. In conclusion, hs-CRP was not
      useful for the prediction of obstructive stenoses in stable subjects. CAC was
      found to be a better predictor of obstructive heart disease than hs-CRP.

PMID- 23174184
TI  - Is the ST-segment elevation in Takotsubo syndrome partially (or even totally) due
      to dyskinesis?

PMID- 23174186
TI  - Structural insights into the mechanism and inhibition of the beta-hydroxydecanoyl
      acyl carrier protein dehydratase from Pseudomonas aeruginosa.
AB  - Fatty acid biosynthesis is an essential component of metabolism in both
      eukaryotes and prokaryotes. The fatty acid biosynthetic pathway of Gram-negative
      bacteria is an established therapeutic target. Two homologous enzymes FabA and
      FabZ catalyze a key step in fatty acid biosynthesis; both dehydrate hydroxyacyl
      fatty acids that are coupled via a phosphopantetheine to an acyl carrier protein
      (ACP). The resulting trans-2-enoyl-ACP is further polymerized in a processive
      manner. FabA, however, carries out a second reaction involving isomerization of
      trans-2-enoyl fatty acid to cis-3-enoyl fatty acid. We have solved the structure
      of Pseudomonas aeruginosa FabA with a substrate allowing detailed molecular
      insight into the interactions of the active site. This has allowed a detailed
      examination of the factors governing the second catalytic step. We have also
      determined the structure of FabA in complex with small molecules (so-called
      fragments). These small molecules occupy distinct regions of the active site and
      form the basis for a rational inhibitor design program.

PMID- 23174185
TI  - Mechanism of replicative DNA polymerase delta pausing and a potential role for
      DNA polymerase kappa in common fragile site replication.
AB  - Common fragile sites (CFSs) are hot spots of chromosomal breakage, and CFS
      breakage models involve perturbations of DNA replication. Here, we analyzed the
      contribution of specific repetitive DNA sequence elements within CFSs to the
      inhibition of DNA synthesis by replicative and specialized DNA polymerases
      (Pols). The efficiency of in vitro DNA synthesis was quantitated using templates
      corresponding to regions within FRA16D and FRA3B harboring AT-rich microsatellite
      and quasi-palindrome (QP) sequences. QPs were predicted to form stems of ~75-100%
      self-homology, separated by 3-9 bases of intervening sequences. Analysis of DNA
      synthesis progression by human Pol delta demonstrated significant synthesis
      perturbation both at [A](n) and [TA](n) repeats in a length-dependent manner and
      at short (<40 base pairs) QP sequences. DNA synthesis by the Y-family polymerase
      kappa was significantly more efficient than Pol delta through both types of
      repetitive elements. Using DNA trap experiments, we show that Pol delta pauses
      within CFS sequences are sites of enzyme dissociation, and dissociation was
      observed in the presence of RFC-loaded PCNA. We propose that enrichment of
      microsatellite and QP elements at CFS regions contributes to fragility by
      perturbing replication through multiple mechanisms, including replicative Pol
      pausing and dissociation. Our finding that Pol delta dissociates at specific CFS
      sequences is significant, since dissociation of the replication machinery and
      inability to efficiently recover the replication fork can lead to fork collapse
      and/or formation of double-strand breaks in vivo. Our biochemical studies also
      extend the potential involvement of Y-family polymerases in CFS maintenance to
      include polymerase kappa.

PMID- 23174187
TI  - Transcription regulation of a yeast gene from a downstream location.
AB  - Mechanisms for coregulation of transcription of tandem genes in yeast remain
      largely speculative. This study focused on inositol-mediated regulation of the
      tandem gene pair SNA3-INO1. While the pattern of regulation of these two genes
      was similar, results showed that intermediate levels of inositol repressed INO1
      and induced SNA3. Results also showed that inositol-mediated regulation of the
      SNA3 gene was not a function of its promoter but occurred from factors within the
      SNA3-INO1 intergenic region. The basic helix-loop-helix proteins, Ino2p and
      Ino4p, mediated this regulation through the upstream activation sequence
      (UAS)(INO) (E-box) sequences in the intergenic region. These results provide a
      model for studying coregulation of yeast tandem genes. This is especially
      significant given that many tandem gene pairs in yeast are coregulated even
      though context-specific UAS sequences are known only for one gene in the pair.

PMID- 23174188
TI  - Computational convergence of the path integral for real dendritic morphologies.
AB  - Neurons are characterised by a morphological structure unique amongst biological
      cells, the core of which is the dendritic tree. The vast number of dendritic
      geometries, combined with heterogeneous properties of the cell membrane, continue
      to challenge scientists in predicting neuronal input-output relationships, even
      in the case of sub-threshold dendritic currents. The Green's function obtained
      for a given dendritic geometry provides this functional relationship for passive
      or quasi-active dendrites and can be constructed by a sum-over-trips approach
      based on a path integral formalism. In this paper, we introduce a number of
      efficient algorithms for realisation of the sum-over-trips framework and
      investigate the convergence of these algorithms on different dendritic
      geometries. We demonstrate that the convergence of the trip sampling methods
      strongly depends on dendritic morphology as well as the biophysical properties of
      the cell membrane. For real morphologies, the number of trips to guarantee a
      small convergence error might become very large and strongly affect computational
      efficiency. As an alternative, we introduce a highly-efficient matrix method
      which can be applied to arbitrary branching structures.

PMID- 23174189
TI  - [Chronic myeloid leukemia and imatinib: Experience at the Lome Campus teaching
      hospital (Togo)].
AB  - BACKGROUND: Chronic myeloid leukemia (CML) is a clonal malignant
      myeloproliferative disorder characterized by the expansion of hematopoietic cells
      carrying the Philadelphia chromosome (t 9.22). Our main objective was to assess
      the efficacy of imatinib in CML patients, measured by their survival. METHODS:
      Over a six-year period (June 2003 through May 2009), 25 patients were seen
      regularly for CML at the Lome Campus teaching hospital. Patients received
      imatinib after diagnosis and underwent regular laboratory monitoring
      (quantification of BCR-ABL ratio by RT-PCR). Patients' survival and treatment
      response were evaluated. RESULTS: Patients' mean age at diagnosis was 40 years
      (range: 9 to 72 years). Men predominated (17 compared with 7 women). Splenomegaly
      was found in 80% of cases. The mean leukocyte level was 188.71 g/L (24.4-350).
      Six patients (24%) had thrombocytosis with a mean platelet count of 491.15 g/L
      (108-2000). Six patients (24%) died after developing accelerated-phase CML or
      blast crisis. Estimated overall survival of patients at 6 years was 60%.
      Molecular biology monitoring detected a secondary G250E mutation with resistance
      to imatinib in one patient. Standard hematological side effects led to reduction
      in imatinib doses. The principal nonhematological side effects were weight gain
      and transient digestible disorders. CONCLUSIONS: At six years after diagnosis,
      imatinib was effective in treating patients with CML, even in sub-Saharan Africa.
      Mutation-induced resistance required regular molecular biological monitoring to
      determine the need to switch to later-generation tyrosine kinase inhibitors.

PMID- 23174190
TI  - Novel players in multiple myeloma pathogenesis: role of protein kinases CK2 and
      GSK3.
AB  - Multiple myeloma (MM) is an incurable plasma cell malignancy, which causes a
      significant morbidity due to organ damage and bone tissue destruction. In recent
      years, novel drugs have become available for MM therapy thanks to a more deepened
      knowledge of this disease's pathogenesis. The perspective of employing targeted
      therapies has considerably changed the expectations on the clinical outcome for
      patients affected by this malignancy and among the targetable molecules
      identified for MM therapy are several protein kinases, which have been proven to
      play relevant roles in supporting malignant plasma cell growth by regulating
      critical signaling cascades and by sustaining oncogenic mechanisms. Protein
      kinase CK2 (formerly known as casein kinase 2) and GSK3 (glycogen synthase kinase
      3) are two multifaceted serine-threonine kinases whose task in the pathogenesis
      of malignant cell growth is increasingly emerging both in solid and blood tumors.
      In hematologic malignancies, CK2 and GSK3 have been shown to play an oncogenic
      function in chronic and acute leukemias as well as in MM. They have been
      demonstrated to act by impinging on pivotal signaling pathways that control
      malignant clone growth. We will herein briefly review the more recent
      advancements on the role of these two kinases in regulating the NF-kappaB, STAT3
      and endoplasmic reticulum (ER) stress/unfolded protein response (UPR) signaling
      in MM and discuss the rationale of using small selective inhibitors as a
      therapeutic strategy to hamper the growth of malignant plasma cells or to improve
      the MM-associated bone disease.

PMID- 23174191
TI  - Chronic myelomonocytic leukemia treatment with azacitidine: what have we learned
      so far?

PMID- 23174192
TI  - Chronic inflammation as a promotor of mutagenesis in essential thrombocythemia,
      polycythemia vera and myelofibrosis. A human inflammation model for cancer
      development?
AB  - The Philadelphia-negative chronic myeloproliferative neoplasms (MPNs) are
      acquired stem cell neoplasms, in which a stem cell lesion induces an autonomous
      proliferative advantage. In addition to the JAK2V617 mutation several other
      mutations have been described. Recently chronic inflammation has been proposed as
      a trigger and driver of clonal evolution in MPNs. Herein, it is hypothesized that
      sustained inflammation may elicit the stem cell insult by inducing a state of
      chronic oxidative stress with elevated levels of reactive oxygen species (ROS) in
      the bone marrow, thereby creating a high-risk microenvironment for induction of
      mutations due to the persistent inflammation-induced oxidative damage to DNA in
      hematopoietic cells. Alterations in the epigenome induced by the chronic
      inflammatory drive may likely elicit a "epigenetic switch" promoting persistent
      inflammation. The perspectives of chronic inflammation as the driver of
      mutagenesis in MPNs are discussed, including early intervention with interferon
      alpha2 and potent anti-inflammatory agents (e.g. JAK1-2 inhibitors, histone
      deacetylase inhibitors, DNA-hypomethylators and statins) to disrupt the self
      perpetuating chronic inflammation state and accordingly eliminating a potential
      trigger of clonal evolution and disease progression with myelofibrotic and
      leukemic transformation.

PMID- 23174193
TI  - Diet and physical activity in pre-school children: a pilot project for
      surveillance in three regions of Italy.
AB  - OBJECTIVE: To test a surveillance system on diet and physical activity based on
      data gathered at well-child visits. DESIGN: Cross-sectional data collection on
      growth, diet, physical activity and sociodemographic variables. SETTING: Offices
      of 179 paediatricians in three Italian regions. SUBJECTS: 26 898 children for a
      total of 32 915 well-child visits at 1, 3, 5-6, 8-9, 12, 18, 24, 36 and 60-72
      months of age. RESULTS: The BMI Z-score was lower than the WHO standard at 1 and
      3 months but higher from 8-9 months onwards. The rates of breast-feeding at 1, 3,
      5-6, 8-9 and 12 months were 88 %, 75 %, 64 %, 52 % and 32 %, respectively, with 5
      % and 3 % continuing up to 24 and 36 months. Exclusive breast-feeding was 64 %,
      54 % and 20 % at 1, 3 and 5-6 months, respectively; 57 % at 5 months and 85 % at
      6 months were given complementary foods. Only 8 % and 10 % of children were
      taking five portions of fruit and vegetables daily, while 47 % and 51 % were
      consuming sugar-sweetened beverages at 36 and 60-72 months, respectively. At 60
      72 months, less than 10 % reported at least 1 h of moderate-to-vigorous physical
      activity on 5-7 d/week, and 32 % watched television or played videogames for more
      than 2 h/d, every day. The majority of paediatricians rated the surveillance
      system as reliable and feasible. CONCLUSIONS: Surveillance for diet and physical
      activity in pre-school children, with data gathered during well-child visits, is
      feasible and potentially useful to plan and evaluate activities for the
      prevention of obesity.

PMID- 23174194
TI  - Influenza vaccination in Turkey: prevalence of risk groups, current vaccination
      status, factors influencing vaccine uptake and steps taken to increase
      vaccination rate.
AB  - Influenza infections cause considerable morbidity and mortality not only during
      the pandemics but also during annual epidemics. Vaccines are the most effective
      tools for preventing the infection. Although World Health Organization (WHO) and
      Ministry of Health (MoH) recommends vaccination for people at increased risk,
      sales data indicate that vaccination rate remains low in Turkey. Vaccine
      recommended groups are well defined and reimbursed in Turkey. However, the
      prevalence of people in risk groups, current vaccination rates and factors
      influencing vaccine uptake which are essential in order to develop and sustain
      effective strategies to increase vaccination rate are not documented. A thorough
      literature review was performed to determine the estimated number of people in
      risk groups, vaccination rates, factors influencing vaccine uptake in Turkey.
      Actions taken by the health authorities in order to increase the vaccine uptake
      among specified risk groups are also summarized. Based on the published
      prevalence rates, current study calculated that there are approximately 27 to 33
      million people in risk groups. In addition, there are 428,000 health care
      providers serving in the public sector who are at increased risk for influenza
      infections. The lowest reported vaccination rate (5.9%) was in the elderly >=65
      years of age and the highest (27.3%) in patients with COPD. Finally, survey
      results indicated that leading factor negatively influencing vaccine uptake was
      disbelief in the effectiveness of vaccine. In order to increase vaccination
      coverage, vaccines are provided to health care providers free of charge and
      reimbursed for those in the risk groups. Realizing the fact that combating flu
      requires multidisciplinary collaboration, a stakeholder network, Grip Platformu,
      has been established in 2011 with the endorsement of the MoH to increase
      influenza awareness and vaccine coverage rates among risk groups in accordance
      with WHO recommendations.

PMID- 23174196
TI  - Kinetics of antibody and memory B cell responses after MMR immunization in
      children and young adults.
AB  - The persistence of antigen-specific memory B-cells (MBCs) in children and young
      adults long time after vaccination against measles, mumps and rubella (MMR) is
      not known. Here we have looked at the Swedish immunization program and examined
      children 1-10 years after the first MMR dose in early childhood, as well as young
      adults 7-18 years after the second dose of MMR. We show that Ab titers and MBCs
      against measles and rubella have different kinetics, indicating that the MBC pool
      and the corresponding Ab titers are regulated independently. These data fit well
      with other findings that continuous IgG secretion comes from long-lived plasma
      cells and not MBCs. We also demonstrate that individuals with low post
      vaccination Ab titers might have an adequate MBC response. It remains to be shown
      if memory B-cells provide the same protection as specific antibodies, but our
      data is a valuable complement to the incomplete knowledge about correlates of
      protection after vaccination.

PMID- 23174195
TI  - How cost effective is universal varicella vaccination in developing countries? A
      case-study from Colombia.
AB  - OBJECTIVE: Varicella vaccination has not been introduced worldwide, especially in
      developing countries. The present study assesses the potential epidemiological
      and economic impact of one-dose and two-dose varicella vaccination schemes in
      Colombia, a south American upper middle-income country. METHODS: A decision-tree
      based model was developed. Varicella cases were estimated based on previous
      reports of seropositivity within the country. Cost per life-year gained (LYG) was
      the main outcome measure. Costs from the health care system perspective were
      expressed in 2008 American dollars. Deterministic and probabilistic sensitivity
      analyses were performed. RESULTS: In Colombia, there would be 700,197 varicella
      cases in an average year plus 60 yearly deaths without vaccination. It was
      estimated that health care costs for all cases during 30 years period could be
      around US $88,734,735 (with discount). Cost per LYG of one-dose vaccination was
      US $2519 and using a two-dose scheme was US $5728. CONCLUSION: Vaccinating
      against varicella in Colombia, an upper middle-income South American country is
      cost-effective under the assumptions used in this study. Decision-makers should
      consider introducing universal varicella vaccination in Colombia, given the
      effectiveness, safety and cost-effectiveness of this intervention.

PMID- 23174197
TI  - The first national adult immunization summit 2012: implementing change through
      action.
AB  - To address lagging vaccine coverage among adults in the United States, over 150
      organizations representing a wide range of immunization partners convened in
      Atlanta, GA from May 15-16, 2012 for the inaugural National Adult Immunization
      Summit. The meeting called for solution-oriented discussion toward improving
      current immunization levels, implementing the 2011 National Vaccine Advisory
      Committee adult immunization recommendations, and capitalizing on new
      opportunities to improve coverage. Provisions in the federal health reform law
      that increase access to preventive services, including immunizations, and the
      increasing numbers of complementary vaccine providers such as pharmacists, create
      new opportunities to increase access for immunization services and improve
      coverage for adults. The Summit organized around five focal areas: empowering
      providers, quality and performance measures, increasing access and collaboration,
      educating patients, and informing decision-makers. These focal areas formed the
      basis of working groups, charged to coordinate efforts by the participating
      organizations to address gaps in the current immunization system. Summit
      participants identified priority themes to address as tasks during the coming
      year, including better communicating the value of immunizations to increase
      demand for immunizations, creating a central repository of resources for
      providers, patients, and others interested in improving adult immunization
      levels, examining performance and quality measures and evaluating means to use
      such measures to motivate vaccine providers, increasing engagement with employer
      and employee groups to increase awareness and demand for vaccinations, improving
      the use of immunization information systems and electronic health reports,
      decreasing barriers to all vaccine providers including pharmacists and community
      vaccinators, decreasing the complexity of the adult vaccine schedule where
      possible, engaging adult immunization champions and leaders in key sectors,
      including adult healthcare provider groups, and encouraging more integration of
      immunization services with other preventive services.

PMID- 23174198
TI  - A PCV2 vaccine based on genotype 2b is more effective than a 2a-based vaccine to
      protect against PCV2b or combined PCV2a/2b viremia in pigs with concurrent PCV2,
      PRRSV and PPV infection.
AB  - The predominant genotype of porcine circovirus (PCV) in the pig population today
      is PCV2b yet PCV2a-based commercial vaccines are considered effective in
      protecting against porcine circovirus associated disease. The objective of this
      study was to compare the ability of PCV2a- and PCV2b-based vaccines to control
      PCV2b viremia in a challenge model that mimics the U.S. field situation. Sixty
      three pigs were randomly assigned to one of eight groups. Sixteen pigs were
      vaccinated with an experimental live-attenuated chimeric PCV1-2a vaccine based on
      genotype 2a and another 16 pigs with a chimeric PCV1-2b vaccine based on genotype
      2b. Challenge was done 28 days post vaccination (dpv) using PCV2b (or a
      combination of PCV2a and PCV2b), porcine reproductive and respiratory syndrome
      virus (PRRSV), and porcine parvovirus (PPV) to mimic what commonly occurs in the
      field. The experiment was terminated 21 days post challenge (dpc) or 49dpv. Pigs
      vaccinated with the chimeric PCV1-2b vaccine had significantly higher levels of
      PCV1-2b viremia and shedding of the PCV1-2b vaccine virus in feces and nasal
      secretions but also a more robust humoral immune response as evidenced by
      significantly higher ELISA S/P ratios compared to the PCV1-2a vaccination.
      Regardless of challenge, the PCV1-2b vaccination significantly reduced the
      prevalence and amount of PCV2 viremia compared to the PCV1-2a vaccination.
      Interestingly, in the non-vaccinated pigs concurrent PCV2a infection resulted in
      clinical disease and increased macroscopic lung lesions compared to pigs
      challenged with PCV2b alone, further supporting the idea that concurrent
      PCV2a/PCV2b infection is necessary for optimal PCV2 replication.

PMID- 23174199
TI  - Dose sparing and enhanced immunogenicity of inactivated rotavirus vaccine
      administered by skin vaccination using a microneedle patch.
AB  - Skin immunization is effective against a number of infectious diseases, including
      smallpox and tuberculosis, but is difficult to administer. Here, we assessed the
      use of an easy-to-administer microneedle (MN) patch for skin vaccination using an
      inactivated rotavirus vaccine (IRV) in mice. Female inbred BALB/c mice in groups
      of six were immunized once in the skin using MN coated with 5 MUg or 0.5 MUg of
      inactivated rotavirus antigen or by intramuscular (IM) injection with 5 MUg or
      0.5 MUg of the same antigen, bled at 0 and 10 days, and exsanguinated at 28 days.
      Rotavirus-specific IgG titers increased over time in sera of mice immunized with
      IRV using MN or IM injection. However, titers of IgG and neutralizing activity
      were generally higher in MN immunized mice than in IM immunized mice; the titers
      in mice that received 0.5 MUg of antigen with MN were comparable or higher than
      those that received 5 MUg of antigen IM, indicating dose sparing. None of the
      mice receiving negative-control, antigen-free MN had any IgG titers. In addition,
      MN immunization was at least as effective as IM administration in inducing a
      memory response of dendritic cells in the spleen. Our findings demonstrate that
      MN delivery can reduce the IRV dose needed to mount a robust immune response
      compared to IM injection and holds promise as a strategy for developing a safer
      and more effective rotavirus vaccine for use among children throughout the world.

PMID- 23174200
TI  - Hepatitis B specific T cell immunity induced by primary vaccination persists
      independently of the protective serum antibody level.
AB  - In 2005, in accordance with recommendations made by the European Medicines
      Agency, the Italian Drug Agency ordered withdrawal of the hexavalent Hexavac((r))
      vaccine (Sanofi Pasteur MSD) from the market. Concerns had been raised about the
      low immunogenicity of the hepatitis B virus component of the vaccine, assessed by
      measurement of serum antibody levels, and its potential consequences on long-term
      protection against hepatitis B infection. We evaluated memory T cell response to
      establish whether there are differences in the protective mechanisms among
      children who had received either Hexavac((r)) or Infanrix-hexa((r))
      (GlaxoSmithKline) as their primary vaccination. Immunological memory was
      determined by measuring the ability of T cells to proliferate and secrete
      IFNgamma by ELISA and intracellular cytokines (IFNgamma and IL-2) when cultured
      with hepatitis B surface antigen (HBsAg). The different memory subsets of T cells
      were also measured. The results indicate that, although they generate different
      serum antibody levels, both vaccines are efficient in generating T recall
      responses in vitro five years after the primary vaccination. The less immunogenic
      Hexavac((r)) vaccine induces a strong T antigen response, as indicated by
      increased blast proliferation and the enhanced presence of memory subsets after
      HBsAg recall stimulation. These findings suggest that cellular immune response
      should be considered alongside serological markers as a surrogate of protection.

PMID- 23174201
TI  - Enhancement of HIV-1 DNA vaccine immunogenicity by BCG-PSN, a novel adjuvant.
AB  - Although the importance of DNA vaccines, especially as a priming immunization has
      been well established in numerous HIV vaccine studies, the immunogenictiy of DNA
      vaccines is generally moderate. Novel adjuvant is in urgent need for improving
      the immunogenicity of DNA vaccine. Polysaccharide and nucleic acid fraction
      extracted by hot phenol method from Mycobacterium bovis bacillus Calmette-Guerin,
      known as BCG-PSN, is a widely used immunomodulatory product in China clinical
      practice. In this study, we evaluated whether the BCG-PSN could serve as a novel
      adjuvant of DNA vaccine to trigger better cellular and humoral immune responses
      against the HIV-1 Env antigen in Balb/C mouse model. The BCG-PSN was mixed with
      10 MUg or 100 MUg of pDRVI1.0gp145 (HIV-1 CN54 gp145 gene) DNA vaccine and
      intramuscularly immunized two or three times. We found that BCG-PSN could
      significantly improve the immunogenicity of DNA vaccine when co-administered with
      DNA vaccine. Further, at the same vaccination schedule, BCG-PSN co-immunization
      with 10 MUg DNA vaccine could elicit cellular and humoral immune responses which
      were comparable to that induced by 100 MUg DNA vaccine alone. Moreover, our
      results demonstrate that BCG-PSN can activate TLR signaling pathways and induce
      Th1-type cytokines secretion. These findings suggest that BCG-PSN can serve as a
      novel and effective adjuvant for DNA vaccination.

PMID- 23174202
TI  - The impact of maternally derived immunity on influenza A virus transmission in
      neonatal pig populations.
AB  - The commonality of influenza A virus (IAV) exposure and vaccination on swine
      farms in the United States ensures that the majority of neonatal pigs will have
      some degree of maternal immunity to IAV. The influence of maternal immunity on
      IAV transmission in neonatal pig populations will impact virus prevalence and
      infection dynamics across pig populations. The main objective of this study was
      to assess the impact of maternally derived immunity on IAV transmission in an
      experimental setting. Neonatal pigs suckled colostrum and derived maternal
      (passive) immunity from sows in one of three treatment groups: (a) non-vaccinated
      control (CTRL) or vaccinated with (b) homologous (PASSV-HOM) or (c) heterologous
      (PASSV-HET) inactivated experimental IAV vaccines. Sentinel neonatal pigs derived
      from the groups above were challenged with IAV via direct contact with an
      experimentally infected pig (seeder pig) and monitored for IAV infection daily
      via nasal swab sampling. A susceptible-infectious-recovered (SIR) experimental
      model was used to obtain and estimate transmission parameters in each treatment
      group via a generalized linear model. All sentinel pigs in the CTRL (30/30) and
      PASSV-HET (30/30) groups were infected with IAV following contact with the seeder
      pigs and the reproduction ratio estimates (95% confidence interval) were 10.4
      (6.6-15.8) and 7.1 (4.2-11.3), respectively. In contrast, 1/20 sentinel pigs in
      the PASSV-HOM group was infected following contact with the seeder pigs and the
      reproduction ratio estimate was significantly lower compared to the CTRL and
      PASSV-HET groups at 0.8 (0.1-3.7). Under the conditions of this study, IAV
      transmission was reduced in neonatal pigs with homologous maternal immunity
      compared to seronegative neonatal pigs and pigs with heterologous maternal
      immunity as defined in this study. This study provides estimates for IAV
      transmission in pigs with differing types of maternal immunity which may describe
      the influence of maternal immunity on IAV prevalence and infection dynamics in
      pig populations.

PMID- 23174203
TI  - The gut microbial metabolome: modulation of cancer risk in obese individuals.
AB  - Obesity is a critical health concern and although genetic factors may predispose
      an individual to become obese, changes in diet and lifestyle over the last few
      decades are likely to be significant contributors. Even so, it has been suggested
      that the causes of the current obesity crisis are not simply explained by changes
      in eating and exercise habits. Evidence suggests that the gut microbiota may play
      an important role in obesity and may be a factor in the development of associated
      disease including diabetes, CVD, non-alcoholic fatty liver disease and cancer.
      There have been tremendous advances in knowledge regarding the composition of
      human gut microbiota, but less is known about their function and role within the
      human host. It is becoming widely accepted that the products of microbial
      metabolism influence human health and disease, particularly with respect to
      immune response and inflammation. However, in most cases, the products of
      microbial metabolism are uncharacterised and their mechanism of action remains
      unknown. This review addresses the role of the metabolites produced by gut
      microbiota in cancer and obesity. It is clear that only if the link between
      microbial diversity and metabolic functionality is firmly established, will the
      mechanism by which gut microbiota maintains health or contributes to disease
      development be elucidated.

PMID- 23174204
TI  - Yikes... spikes! Exposed tracheal cartilaginous spikes at EGD from malignant
      tracheoesophageal fistula.

PMID- 23174205
TI  - An uncommon cause of esophageal ulcer: a diagnostic pitfall.

PMID- 23174206
TI  - Findings from the Garner-paradigm do not support the "how" versus "what"
      distinction in the visual brain.
AB  - In this study we challenge the widely accepted suggestion that visual perception,
      but not visual control of action, processes object shape in a holistic manner
      (Ganel and Goodale, 2003, Nature). The finding that perceptual judgments but not
      visuomotor acts, such as grasping are affected by variations along an irrelevant
      object dimension (Garner-interference) is held up as strong evidence that vision
      for perception and vision for action are processed within different areas of the
      human brain. Here, we suggest that it is possible to explain the observed
      dissociation without recourse to functional and/or neurological dissociations
      between vision for perception and vision for action. In three experiments, we
      demonstrate that it is possible to either elicit or eliminate a Garner
      interference effect in a perceptual task by varying the temporal profile of the
      perceptual response. Additionally, we show that it is also possible to induce a
      Garner-interference effect in a visuomotor task when the task is designed in a
      way which discourages participants from making online changes to their ongoing
      motor response. We suggest that the crucial factor for the occurrence of a Garner
      interference is whether reaction time is measured such that it actually reflects
      the total duration of the response selection processes or not. According to our
      results, it seems therefore no longer appropriate to use the Garner-paradigm in
      support of the notion that the processing mechanisms in perception and action are
      dissociated.

PMID- 23174207
TI  - Mental transformations of spatial stimuli in humans and in monkeys: rotation vs.
      translocation.
AB  - We studied the ability of monkeys and humans to orient in one spatial frame
      ("response frame") according to abstract spatial stimuli presented in another
      spatial frame ("stimulus frame"). The stimuli were designed as simple maps of the
      "response space". We studied how the transformations of these stimuli affected
      the performance. The subjects were trained to choose a particular position in the
      response frame - either on a touch screen (monkeys) or on a keyboard (humans) -
      according to schematic spatial stimuli presented on the stimulus screen. The
      monkeys responded by touching one of four circles shown in corners of a rectangle
      displayed on the touch screen. The correct position was signaled by the stimulus
      ("map") presented on the stimulus screen. The map was a complementary rectangle,
      but only with one circle shown ("pointer"). The position of this circle indicated
      the correct position in the response frame. In the first experiment we only
      manipulated stimuli presented on the computer screen. The "map" was originally
      shown in the same position and orientation as the "response pattern" but later
      the position and the rotation of the map on the screen were changing. Such
      transformations of the stimuli allow us to study the mental operations that the
      animals performed and how particular mental transformations mutually differed. In
      the second experiment we tested whether the monkeys relied more on stimuli
      presented on the screen or on the surrounding stable environment and objects. We
      compared the performance of animals in tasks with rotated virtual maps in a
      stable surrounding environment with the performance in tasks where we rotated the
      surrounding frame (computer monitor), whereas the stimuli on the screen remained
      stable. In the third experiment we tested human subjects in analogous tests to
      compare the ability and cognitive strategies of monkeys and humans in this task.
      We showed that the mental strategies that monkeys used for orientation in one
      spatial frame according to the map presented in the other spatial frame depended
      on the type of stimulus manipulation. We demonstrated that for monkeys there was
      a difference between solving "mental rotation" and "mental translocation" in this
      experimental design. We showed that humans were able both to mentally rotate and
      translocate the displayed stimuli. However, the mental rotation was more
      difficult than mental translocation also for them. These experiments help us to
      understand how the monkeys perceive the abstract spatial information, create the
      representation of space and how they transform the information about the position
      obtained from one spatial frame into another. The comparison between humans and
      monkeys allows us to study this cognitive ability in phylogeny.

PMID- 23174208
TI  - A drug-paired taste cue elicits withdrawal and predicts cocaine self
      administration.
AB  - Addiction is a chronic disease where periods of abstinence are riddled with
      instances of craving, withdrawal, and eventual relapse to escalated drug use.
      Cues previously associated with drug use can have a deleterious effect on this
      cycle by precipitating withdrawal symptoms. Here we focus specifically on the
      relationship between avoidance of a drug-paired taste cue and the ability of the
      drug-paired cue to elicit withdrawal and, ultimately, drug seeking and taking. We
      used a rat model of drug addiction and naloxone-induced loss of body weight to
      test whether a taste cue elicits withdrawal in anticipation of drug availability.
      Experiment 1 investigated the ability of a taste cue to elicit signs of
      withdrawal when it predicted experimenter-administered morphine (15 mg/kg, i.p.).
      In Experiment 2, a saccharin taste cue was paired with the opportunity to
      actively self-administer cocaine (0.167 mg/infusion, i.v.). The results show that
      presentation of a morphine- or cocaine-paired taste cue is sufficient to elicit
      naloxone-induced withdrawal symptoms, and greater withdrawal predicts greater
      cocaine self-administration in rats.

PMID- 23174209
TI  - Inhibition of phosphodiesterase-5 rescues age-related impairment of synaptic
      plasticity and memory.
AB  - Aging is characterized by a progressive cognitive decline that leads to memory
      impairment. Because the cyclic nucleotide cascade is essential for the integrity
      of synaptic function and memory, and it is down-regulated during aging and in
      neurodegenerative disorders, we investigated whether an increase in cGMP levels
      might rescue age-related synaptic and memory deficits in mice. We demonstrated
      that acute perfusion with the phosphodiesterase-5 inhibitor sildenafil (50 nM)
      ameliorated long-term potentiation in hippocampal slices from 26-30-month-old
      mice. Moreover, chronic intraperitoneal injection of sildenafil (3mg/kg for 3
      weeks) improved age-related spatial learning and reference memory as tested by
      the Morris Water Maze, and recognition memory as tested by the Object Recognition
      Test. Finally, sildenafil restored central cAMP responsive element-binding
      protein (CREB) phosphorylation, which is crucial for synaptic plasticity and
      memory. Our data suggest that inhibition of phosphodiesterase-5 may be beneficial
      to treat age-related cognitive dysfunction in a physiological mouse model of
      aging.

PMID- 23174210
TI  - Neural mechanisms underlying the changes in ipsilateral primary motor cortex
      excitability during unilateral rhythmic muscle contraction.
AB  - The aim of this study was to investigate the neural mechanisms underlying the
      changes in the ipsilateral primary motor cortex (ipsi-M1) excitability induced
      during the unilateral rhythmic muscle contraction of the first dorsal
      interosseous (FDI) (rhythmic contraction) muscle with three different frequencies
      of auditory cues (1, 2, and 3 Hz). The effect of different frequencies of
      unilateral rhythmic contraction on changes in the ipsi-M1 excitability was
      assessed using a single-pulse transcranial magnetic stimulation (TMS) technique
      when subjects were performing the unilateral rhythmic contractions according to
      each auditory cue frequency. After that, the changes in short intracortical
      inhibition (SICI)/facilitation (ICF), long intracortical inhibition (LICI) within
      the ipsi-M1, and interhemispheric inhibition (IHI), as well as dorsal premotor
      cortex to M1 (PMd-M1), and dorsolateral prefrontal cortex to M1 (DLPFC-M1)
      connectivity from the contralateral hemisphere to the ipsi-M1 were assessed using
      paired-pulse TMS techniques. The motor evoked potentials (MEP) induced in the
      right FDI were recorded. In the results, the ipsi-M1 excitability induced in
      response to single-pulse TMS was significantly decreased in the 2 Hz conditions,
      compared with the 1Hz and 3Hz conditions. Furthermore, PMd-M1 connectivity and
      LICI were significantly modulated depending on the frequency of the unilateral
      rhythmic contraction. In contrast, the changes in the SICI, ICF, IHI, and DLPFC
      M1 were not directly associated with the rhythm frequency. These results suggest
      that PMd-M1 connectivity and LICI within the ipsi-M1 are likely to preferentially
      operate to modulate ipsi-M1 excitability during the performance of unilateral
      rhythmic contraction with different frequencies.

PMID- 23174211
TI  - Selective increase in the association of the beta2 adrenergic receptor, beta
      Arrestin-1 and p53 with Mdm2 in the ventral hippocampus one month after
      underwater trauma.
AB  - Chronic infusion of mice with a beta2 adrenergic receptor (beta2AR) analog was
      shown to cause long-term DNA damage in a pathway which involves beta Arresin-1
      mediated activation of Mdm2 and subsequent degradation of the tumor suppressor
      protein p53. The objective of the present study was to test whether a single
      acute stress, which manifests long lasting changes in behavior, affects the
      interaction of Mdm2 with p53, beta2AR, and beta Arrestin-1 in the dorsal and
      ventral hippocampal CA1. Adult rats were subject to underwater trauma, a brief
      forceful submersion under water and tested a month later for behavioral and
      biochemical changes. Elevated plus maze tests confirmed that animals that
      experienced the threat of drowning present heightened levels of anxiety one month
      after trauma. An examination of the CA1 hippocampal areas of the same rats showed
      that underwater trauma caused a significant increase in the association of Mdm2
      with beta2AR, beta Arrestin-1, and p53 in the ventral but not dorsal CA1. Our
      results provide support for the idea that stress-related events may result in
      biochemical changes restricted to the ventral 'emotion-related' parts of the
      hippocampus.

PMID- 23174212
TI  - Predicting longevity of iron permeable reactive barriers using multiple iron
      deactivation models.
AB  - In this study we investigate the model uncertainties involved in predicting long
      term permeable reactive barrier (PRB) remediation efficiency based on a lab-scale
      column experiment under accelerated flow conditions. A PRB consisting of 20% iron
      and 80% sand was simulated in a laboratory-scale column and contaminated
      groundwater was pumped into the column for approximately 1 year at an average
      groundwater velocity of 3.7 E-1 m d(-1). Dissolved contaminants (PCE, TCE, cis
      DCE, trans-DCE and VC) and inorganic (Ca(2+), Fe(2+), TIC and pH) concentrations
      were measured in groundwater sampled at different times and at eight different
      distances along the column. These measurements were used to calibrate a multi
      component reactive transport model, which subsequently provided predictions of
      long-term PRB efficiency under reduced flow conditions (i.e., groundwater
      velocity of 1.4 E-3m d(-1)), representative of a field site of interest in this
      study. Iron reactive surface reduction due to mineral precipitation and iron
      dissolution was simulated using four different models. All models were able to
      reasonably well reproduce the column experiment measurements, whereas the
      extrapolated long-term efficiency under different flow rates was significantly
      different between the different models. These results highlight significant model
      uncertainties associated with extrapolating long-term PRB performance based on
      lab-scale column experiments. These uncertainties should be accounted for at the
      PRB design phase, and may be reduced by independent experiments and field
      observations aimed at a better understanding of reactive surface deactivation
      mechanisms in iron PRBs.

PMID- 23174213
TI  - Osteopetrosis, osteopetrorickets and hypophosphatemic rickets differentially
      affect dentin and enamel mineralization.
AB  - Osteopetrosis (OP) is an inherited disorder of defective bone resorption, which
      can be accompanied by impaired skeletal mineralization, a phenotype termed
      osteopetrorickets (OPR). Since individuals with dysfunctional osteoclasts often
      develop osteomyelitis of the jaw, we have analyzed, if dentin and enamel
      mineralization are differentially affected in OP and OPR. Therefore, we have
      applied non-decalcified histology and quantitative backscattered electron imaging
      (qBEI) to compare the dental phenotypes of Src(-/-), oc/oc and Hyp(-/0) mice,
      which serve as models for OP, OPR and hypophosphatemic rickets, respectively.
      While both, Src(-/-) and oc/oc mice, were characterized by defects of molar root
      formation, only oc/oc mice displayed a severe defect of dentin mineralization,
      similar to Hyp(-/0) mice. Most importantly, while enamel thickness was not
      affected in either mouse model, the calcium content within the enamel phase was
      significantly reduced in oc/oc, but not in Src(-/-) or Hyp(-/0) mice. Taken
      together, these data demonstrate that dentin and enamel mineralization are
      differentially affected in Src(-/-) and oc/oc mice. Moreover, since defects of
      dental mineralization may trigger premature tooth decay and thereby osteomyelitis
      of the jaw, they further underscore the importance of discriminating between OP
      and OPR in the respective individuals.

PMID- 23174214
TI  - Accuracy of ICD-9 codes to identify nonunion and malunion and developing
      algorithms to improve case-finding of nonunion and malunion.
AB  - OBJECTIVE: To evaluate the accuracy of using ICD-9 codes to identify nonunions
      (NU) and malunions (MU) among adults with a prior fracture code and to explore
      case-finding algorithms. STUDY DESIGN: Medical chart review of potential NU
      (N=300) and MU (N=288) cases. True NU cases had evidence of NU and no evidence of
      MU in the chart (and vice versa for MUs) or were confirmed by the study
      clinician. Positive predictive values (PPV) were calculated for ICD-9 codes. Case
      finding algorithms were developed by a classification and regression tree
      analysis using additional automated data, and these algorithms were compared to
      true case status. SETTING: Group Health Cooperative. RESULTS: Compared to true
      cases as determined from chart review, the PPV of ICD-9 codes for NU and MU were
      89% (95% CI, 85-92%) and 47% (95% CI, 41-53%), respectively. A higher proportion
      of true cases (NU: 95%; 95% CI, 90-98%; MU: 56%; 95% CI, 47-66%) were found among
      subjects with 1+ additional codes occurring in the 12months following the initial
      code. There was no case-finding algorithm for NU developed given the high PPV of
      ICD-9 codes. For MU, the best case-finding algorithm classified people as an MU
      case if they had a fracture in the forearm, hand, or skull and had no visit with
      an NU diagnosis code in the 12-month post MU diagnosis. PPV for this MU case
      finding algorithm increased to 84%. CONCLUSIONS: Identifying NUs with its ICD-9
      code is reasonable. Identifying MUs with automated data can be improved by using
      a case-finding algorithm that uses additional information. Further validation of
      the MU algorithms in different populations is needed, as well as exploration of
      its performance in a larger sample.

PMID- 23174215
TI  - Autosomal dominant hypophosphatemic rickets in an 85 year old woman:
      characterization of her disease from infancy through adulthood.
AB  - BACKGROUND: Autosomal dominant hypophosphatemic rickets (ADHR) is a rare genetic
      disorder of phosphate homeostasis characterized, when severely expressed, by
      osteomalacia, suppressed levels of calcitriol, and renal phosphate wasting due to
      elevated levels of fibroblast growth factor 23 (FGF23). The disease is caused by
      heterozygous FGF23 mutations at the RXXR site that prevent cleavage of the intact
      hormone. OBJECTIVES: An FGF23 mutation was identified in the proband an 85-year
      old woman with elevated FGF23 levels, and her clinical course was characterized.
      Medical records revealed she was treated for rickets as an infant. She was then
      asymptomatic until soon after her 4th pregnancy, when she suffered incapacitating
      bone pain and weakness, age 37. Symptoms remitted with brief treatment. RESULTS:
      The proband and one son, but not other family members, were found to be
      heterozygous for the R176Q mutation in FGF23. Expression of this germ line
      mutation was strikingly different in both individuals in terms of skeletal
      health, FGF23 levels and disease activity. CONCLUSIONS: The identified FGF23
      mutation in two members of this family raises questions about molecular
      mechanisms that have led to intermittent increases in FGF23 synthesis and
      secretion, and disease expression.

PMID- 23174216
TI  - Conceptual evaluation of population health surveillance programs: method and
      example.
AB  - Veterinary and public health surveillance programs can be evaluated to assess and
      improve the planning, implementation and effectiveness of these programs.
      Guidelines, protocols and methods have been developed for such evaluation. In
      general, they focus on a limited set of attributes (e.g., sensitivity and
      simplicity), that are assessed quantitatively whenever possible, otherwise
      qualitatively. Despite efforts at standardization, replication by different
      evaluators is difficult, making evaluation outcomes open to interpretation. This
      ultimately limits the usefulness of surveillance evaluations. At the same time,
      the growing demand to prove freedom from disease or pathogen, and the Sanitary
      and Phytosanitary Agreement and the International Health Regulations require
      stronger surveillance programs. We developed a method for evaluating veterinary
      and public health surveillance programs that is detailed, structured, transparent
      and based on surveillance concepts that are part of all types of surveillance
      programs. The proposed conceptual evaluation method comprises four steps: (1)
      text analysis, (2) extraction of the surveillance conceptual model, (3)
      comparison of the extracted surveillance conceptual model to a theoretical
      standard, and (4) validation interview with a surveillance program designer. This
      conceptual evaluation method was applied in 2005 to C-EnterNet, a new Canadian
      zoonotic disease surveillance program that encompasses laboratory based
      surveillance of enteric diseases in humans and active surveillance of the
      pathogens in food, water, and livestock. The theoretical standard used for
      evaluating C-EnterNet was a relevant existing structure called the "Population
      Health Surveillance Theory". Five out of 152 surveillance concepts were absent in
      the design of C-EnterNet. However, all of the surveillance concept relationships
      found in C-EnterNet were valid. The proposed method can be used to improve the
      design and documentation of surveillance programs. It complements existing
      surveillance evaluation methods. Conceptual evaluation is not a performance
      oriented evaluation method and so it is particularly useful for surveillance
      programs with a valid conceptual framework but limited technical capacity and
      resources. Such programs would be penalized using existing performance-based
      evaluation methods. Applying conjointly the conceptual evaluation along with
      existing performance-oriented evaluation methods will better judge the worth of
      surveillance programs. We recommend developing a comprehensive surveillance
      evaluation framework for veterinary and public health surveillance programs that
      integrates all existing surveillance evaluation tools and provides an appropriate
      way to evaluate various types of surveillance programs.

PMID- 23174217
TI  - Hock lesion epidemiology in cubicle housed dairy cows across two breeds, farming
      systems and countries.
AB  - This cross-sectional study examined various aspects of cubicle design and
      management in terms of their potential as risk factors for hock lesions, using an
      epidemiological approach. Cubicle dairy farms in Germany and Austria with
      Holstein Friesian or Simmental cows were visited during the winter housing
      season. 105 farms and 3691 cows were included in the analysis which consisted of
      three steps: bifactorial regression, regression trees and multiple linear
      regression. The mean farm prevalence of hock lesions, i.e. scabs, wounds, and
      swellings was 50%, with a range from 0 to 100%. The final model contained eight
      factors which were largely related to lying comfort and explained 75% of the
      variance. The presence of a curb turned out to be the most influential beneficial
      factor. Additionally, there were fewer hock lesions when cows were housed with
      deep bedded cubicles compared to cubicles without deep bedding. Other factors in
      the regression model were softness and length of the lying surface and height of
      free space under cubicle partitions, the proportion of overconditioned cows and a
      variable encoding three different combinations of region, husbandry system
      (organic and conventional) and breed. Independently from the risk factor model
      hock lesions were positively correlated with lameness at herd level as well as at
      animal level. This probably results from related risk factors for both
      conditions. It can be concluded that lying comfort of dairy cows should be
      improved in order to prevent hock lesions. In addition, preventive measures for
      hock lesions at the same time have a potential of reducing lameness and thus to
      improve cow welfare in several aspects.

PMID- 23174219
TI  - An audit of prescribing for type 2 diabetes in primary care: optimising the role
      of the community pharmacist in the primary healthcare team.
AB  - The Government has identified that the pharmacist should have greater involvement
      in the management of long-term conditions. The aim of this audit was to determine
      the adherence to National Institute for Health and Clinical Excellence guidelines
      for type 2 diabetes patients and identify whether there is a potential role for
      pharmacists in their long-term management. All prescribing, in 194 patients, was
      within guidance for anti-hyperglycaemics. In all, 87.4% of patients prescribed an
      anti-hypertensive were prescribed an angiotensin-converting enzyme inhibitor or
      equivalent. A large number of patients remain uncontrolled with respect to blood
      glucose or blood pressure. There are four potential reasons for this: patients
      require additional therapy; current therapy has not been optimised; current
      therapy is not working; or the patient is not fully adherent. Therefore, there
      may be a role for the pharmacist either in therapy optimisation or improving
      patient adherence to current therapy in order to support more patients reaching
      national targets.

PMID- 23174218
TI  - Effects of systemic administration or intrabursal injection of serotonin on
      puberty, first ovulation and follicular development in rats.
AB  - To elucidate the role of serotonin in the onset of puberty, the effects of both
      systemic and in-ovarian bursa administration of serotonin on the neuroendocrine
      mechanism that modulates the onset of puberty, follicular development and first
      ovulation were evaluated. Two experiments were carried out. For the first, 25 or
      37.5 mg kg-1 of bodyweight of serotonin creatinine sulfate was administered by a
      subcutaneous route to 30-day-old female rats. In the second experiment, serotonin
      creatinine sulfate was administered directly into the ovarian bursa of 34-day-old
      female rats. Systemic administration of 25 or 37.5 mg kg-1 of serotonin
      creatinine sulfate induced a delay in the ages of vaginal opening and first
      vaginal oestrus, a decrease in the number of ovulating animals, and serum
      concentrations of FSH, LH, oestradiol and progesterone. An increase in the number
      of Class 3 (>500 MUm) and atretic follicles was observed in the ovaries of these
      animals. The administration of serotonin creatinine sulfate in the ovarian bursa
      did not modify the onset of puberty and ovulation, but a reduced serum
      concentration of oestradiol was observed. Our results suggest that serotonin acts
      on the components of the hypothalamus-hypophysis-ovary axis by modulating
      follicular development, ovarian functions and the onset of puberty.

PMID- 23174220
TI  - Monogalactosyl diacylglycerol, a replicative DNA polymerase inhibitor, from
      spinach enhances the anti-cell proliferation effect of gemcitabine in human
      pancreatic cancer cells.
AB  - BACKGROUND: Gemcitabine (GEM) is used to treat various carcinomas and represents
      an advance in pancreatic cancer treatment. In the screening for DNA polymerase
      (pol) inhibitors, a glycoglycerolipid, monogalactosyl diacylglycerol (MGDG), was
      isolated from spinach. METHODS: Phosphorylated GEM derivatives were chemically
      synthesized. In vitro pol assay was performed according to our established
      methods. Cell viability was measured using MTT assay. RESULTS: Phosphorylated
      GEMs inhibition of mammalian pol activities assessed, with the order of their
      effect ranked as: GEM-5'-triphosphate (GEM-TP) > GEM-5'-diphosphate > GEM-5'
      monophosphate > GEM. GEM suppressed growth in the human pancreatic cancer cell
      lines BxPC-3, MIAPaCa2 and PANC-1 although phospholylated GEMs showed no effect
      MGDG suppressed growth in these cell lines based on its selective inhibition of
      replicative pol species. Kinetic analysis showed that GEM-TP was a competitive
      inhibitor of pol alpha activity with nucleotide substrates, and MGDG was a
      noncompetitive inhibitor with nucleotide substrates. GEM combined with MGDG
      treatments revealed synergistic effects on the inhibition of DNA replicative pols
      alpha and gamma activities compared with GEM or MGDG alone. In cell growth
      suppression by GEM, pre-addition of MGDG significantly enhanced cell
      proliferation suppression, and the combination of these compounds was found to
      induce apoptosis. In contrast, GEM-treated cells followed by MGDG addition did
      not influence cell growth. CONCLUSIONS: GEM/MGDG enhanced the growth suppression
      of cells based on the inhibition of pol activities. GENERAL SIGNIFICANCE: Spinach
      MGDG has great potential for development as an anticancer food compound and could
      be an effective clinical anticancer chemotherapy in combination with GEM.

PMID- 23174221
TI  - Beta-catenin signaling induces CYP1A1 expression by disrupting adherens junctions
      in Caco-2 human colon carcinoma cells.
AB  - BACKGROUND: The aryl hydrocarbon (Ah) receptor is one of the best known ligand
      activated transcription factors. The present study has focused on the wound
      healing process on Ah receptor function. METHODS: Depletion of calcium from
      culture medium of Caco-2 human colon carcinoma cells by transfer to Minimal
      Essential Medium (Spinner Modification; S-MEM) destroyed adherens junctions and
      the cells were used as the model of wound-healing process. RESULTS: Calcium
      depletion induced both nuclear translocation of the Ah receptor, and increased
      expression of CYP1A1 and Slug mRNAs in Caco-2 cells. However, expression of Slug
      mRNA was not significantly induced by treatment with 2,3,7,8-tetrachlorodibenzo-p
      dioxin. Knockdown of the Ah receptor and treatment with Ah receptor antagonists
      decreased level of CYP1A1 mRNA. The fragment of E-cadherin released by gamma
      secretase was not involved in induction of CYP1A1 mRNA following S-MEM treatment.
      Knockdown of beta-catenin increased levels of Ah receptor mRNA, which may be
      attributable to direct or indirect involvement of beta-catenin in suppression of
      the Ah receptor gene. CONCLUSIONS: Our results suggest that mRNA induction of
      some genes by destruction of adherens junctions depends on the Ah receptor. beta
      Catenin, one of the components of the adherens junction, was released from the E
      cadherin complex, which resulted in its increased interaction with the Ah
      receptor, and was translocated into the nucleus, and consequently the target
      genes would be transcribed. GENERAL SIGNIFICANCE: Our observations suggest that
      some aspects of the molecular mechanism of wound healing involve the Ah receptor.

PMID- 23174222
TI  - Percutaneous device closure of aortico-left ventricular tunnel using Amplatzer
      vascular plug III.
AB  - Aortico-left ventricular tunnel is a rare congenital heart defect. Reports on
      successful device closure of these defects are scarce. We are reporting the first
      case of device closure of aortico-left ventricular tunnel using an Amplatzer
      vascular plug III.

PMID- 23174223
TI  - Early in life bladder inflammation alters opioid peptide content in the spinal
      cord and bladder of adult female rats.
AB  - PURPOSE: Previous research suggests that a failure of opioid inhibition may
      contribute to chronic bladder pain. We determined how acute adult and/or prior
      early in life exposure to bladder inflammation alters the adult content of
      endogenous opioid peptides in the bladder, spinal cord and blood. MATERIALS AND
      METHODS: Inflammation was induced by intravesical administration of zymosan.
      Female Sprague-Dawley(r) rats were exposed to anesthesia only or zymosan early in
      life (postnatal days 14 to 16) and anesthesia only or zymosan as adults (ages 12
      to 17 weeks). Thoracolumbar and lumbosacral segments of the spinal cord, and
      blood and bladders were collected 24 hours after adult treatment. Opioid peptide
      content was measured using enzyme-linked immunosorbent assay. RESULTS: Early in
      life bladder inflammation alone produced a chronic increase in dynorphin A (1-17)
      in the lumbosacral spinal cord. When early in life inflammation was followed by
      adult re-inflammation, spinal cord dynorphin remained unchanged but bladder
      dynorphin was decreased. In addition, early in life inflammation combined with
      adult bladder inflammation decreased endomorphin-2 content in the thoracolumbar
      spinal cord. Neither early in life nor adult bladder inflammation affected
      thoracolumbar dynorphin, serum dynorphin, lumbosacral endomorphin-2 or plasma
      beta-endorphin. CONCLUSIONS: Several opioid peptides were measured using enzyme
      linked immunosorbent assay following early in life and adult bladder
      inflammation. The changes observed are consistent with the view that early in
      life bladder inflammation alone can chronically alter spinal cord peptide
      content. When coupled with adult re-inflammation, these changes could set the
      neurochemical stage to support bladder hypersensitivity.

PMID- 23174224
TI  - Data for free--can an electronic medical record provide outcome data for
      incontinence/prolapse repair procedures?
AB  - PURPOSE: We determined whether a custom computer program can improve the
      extraction and accuracy of key outcome measures from progress notes in an
      electronic medical record compared to a traditional data recording system for
      incontinence and prolapse repair procedures. MATERIALS AND METHODS: Following
      institutional review board approval, progress notes were exported from the Epic
      electronic medical record system for outcome measure extraction by a custom
      computer program. The extracted data (D1) were compared against a manually
      maintained outcome measures database (D2). This work took place in 2 phases.
      During the first phase, volatile data such as questionnaires and standardized
      physical examination findings using the POP-Q (pelvic organ prolapse
      quantification) system were extracted from existing progress notes. The second
      phase used a progress note template incorporating key outcome measures to
      evaluate improvement in data accuracy and extraction rates. RESULTS: Phase 1
      compared 6,625 individual outcome measures from 316 patients in D2 to 3,534
      outcome measures extracted from progress notes in D1, resulting in an extraction
      rate of 53.3%. A subset of 3,763 outcome measures from D1 was created by
      excluding data that did not exist in the extraction, yielding an accuracy rate of
      93.9%. With the use of the template in phase 2, the extraction rate improved to
      91.9% (273 of 297) and the accuracy rate improved to 100% (273 of 273).
      CONCLUSIONS: In the field of incontinence and prolapse, the disciplined use of an
      electronic medical record template containing a preestablished set of key outcome
      measures can provide the ideal interface between required documentation and
      clinical research.

PMID- 23174225
TI  - The Penile Perception Score: an instrument enabling evaluation by surgeons and
      patient self-assessment after hypospadias repair.
AB  - PURPOSE: Studies of the outcome of hypospadias repair must document quality,
      including assessment of complications and appraisal of appearance. To our
      knowledge the Pediatric Penile Perception Score is the first validated instrument
      for the outcome assessment of hypospadias repair in prepubertal males by surgeons
      and patients. We validated the instrument for adult genitalia. MATERIALS AND
      METHODS: Standardized photographic documentation was prepared for 19 men after
      hypospadias repair and 3 with normal genitalia after circumcision. This was sent
      to 21 urologists, who rated the outcome with a questionnaire comprising items on
      the penile meatus, glans, shaft skin and general appearance. Each item was rated
      with a 4-point Likert scale. The Penile Perception Score is a sum score of all
      items. Patients were asked to provide a self-assessment with the same instrument.
      RESULTS: When calculated with the ICC and the rank correlation using Kendall W,
      concordance among urologist scores was fair and good (0.46 and 0.64,
      respectively, p <0.001). Instrument stability was 0.78, indicating good
      reproducibility. Using the Spearman rank correlation coefficient general
      appearance correlated well with single items, including the meatus (r = 0.93, p =
      0.000), glans (r = 0.92, p = 0.000) and shaft skin (r = 0.89, p = 0.000). No
      significant differences were found between patient and urologist Penile
      Perception Scores. CONCLUSIONS: The Penile Perception Score is a reliable
      instrument for urologist assessment and self-assessment of postpubertal genitalia
      after hypospadias repair. The instrument can be recommended for all age groups
      because it was previously validated for the pediatric population.

PMID- 23174226
TI  - The influence of promoter -202 A/C polymorphism (rs2854744) of the IGFBP-3 gene
      on erectile dysfunction risk and serum levels of IGF-I and IGFBP-3.
AB  - PURPOSE: We studied whether the IGFBP-3 gene polymorphism rs2854744 is associated
      with erectile dysfunction. MATERIALS AND METHODS: We investigated the association
      of this polymorphism with erectile dysfunction in 176 cases and 352 controls. We
      genotyped rs2854744 using polymerase chain reaction-restriction fragment length
      polymorphism. Circulating concentrations of IGF-I and IGFBP-3 were also measured.
      RESULTS: Allelic frequencies were 0.474 (A allele) and 0.526 (C allele) in men
      with erectile dysfunction, and 0.457 (A allele) and 0.543 (C allele) in normal
      controls (adjusted OR 1.74, 95% CI 0.82-2.43, p = 0.08). The frequency of the
      IGFBP-3 A-202C polymorphism genotype was 0.273 (CC), 0.506 (AC) and 0.221 (AA) in
      the case group, and 0.296 (CC), 0.494 (AC) and 0.210 (AA) in the control group
      (chi-square test p = 0.08). Neither the IGFBP-3 A-202C polymorphism nor serum IGF
      I and IGFBP-3 levels were significantly associated with the risk of erectile
      dysfunction. Carriers of the AA genotype had the highest age adjusted serum IGFBP
      3. This demonstrated a stepwise decrease in the presence of 1 or 2 copies of the
      C allele (mean +/- SD 4,541 +/- 796.2, 3,552 +/- 642.4 and 3,314 +/- 669.3 ng/ml,
      respectively). There was a positive correlation between serum IGFBP-3 and serum
      IGF-I concentrations (Spearman correlation coefficient r = 0.34, p for trend =
      0.001). CONCLUSIONS: The IGFBP-3 gene A-202C polymorphism does not modulate the
      risk of erectile dysfunction.

PMID- 23174227
TI  - Loss of heterozygosity analysis at different chromosome regions in Wilms tumor
      confirms 1p allelic loss as a marker of worse prognosis: a study from the Italian
      Association of Pediatric Hematology and Oncology.
AB  - PURPOSE: The specific aims of the AIEOP-TW-2003 protocol included prospectively
      investigating a possible association of tumor loss of heterozygosity with
      outcomes in children treated for Wilms tumor. MATERIALS AND METHODS: We analyzed
      125 unilateral favorable histology Wilms tumors registered between 2003 and 2008
      in the Italian cooperative protocol for microsatellite markers mapped to
      chromosomes 1p, 7p, 11q, 16q and 22q. RESULTS: The 3-year disease-free survival
      and overall survival probabilities were 0.87 (95% CI 0.81-0.93) and 0.98 (95% CI
      0.96-1.0), respectively. Loss of heterozygosity at 1p was significantly
      associated with a worse disease-free survival (probability 0.67 for patients with
      and 0.92 for those without 1p loss of heterozygosity, p = 0.0009), as confirmed
      also by multivariate analysis adjusting for tumor stage and patient age at
      diagnosis. There was no difference in disease-free survival probability among
      children with loss of heterozygosity in the other chromosomal regions tested. The
      worse outlook for children older than 2 years at diagnosis did not seem to be
      influenced by the loss of heterozygosity patterns considered. CONCLUSIONS:
      Chromosome 1p loss of heterozygosity seems to be a risk factor for nonanaplastic
      Wilms tumor, possibly regardless of other clinical factors. Our findings were
      uninformative regarding loss of heterozygosity in the other chromosomal regions
      tested.

PMID- 23174228
TI  - Colon enemas for fecal incontinence in patients with spina bifida.
AB  - PURPOSE: We studied the use of colon enemas in achieving fecal pseudocontinence
      in patients with spina bifida to define the variables associated with success.
      MATERIALS AND METHODS: Questionnaires were individually filled out by all
      patients with spina bifida using colon enemas at our Spina Bifida Reference
      Center between October 2009 and June 2010. Patient age, type of enema, volume
      required, evacuation time, followup, continence and independence were recorded.
      Fecal pseudocontinence was defined as no involuntary stool loss during the last 6
      months. Social continence was defined as involuntary stool loss less than once
      monthly. Children are routinely seen at the reference center, while adults are
      seen on request. RESULTS: A total of 25 children and 15 adults with spina bifida
      were studied. Median volume required was 1 liter (range 0.5 to 2) in children and
      1.5 liters (0.75 to 3) in adults. Median evacuation time was 30 minutes (range 15
      to 60) in children and 60 minutes (30 to 120) in adults. Fecal continence was
      achieved in 76% of children (19 of 25) and 60% of adults (9 of 15), and social
      continence in 88% of children (23 of 25) and 67% of adults (10 of 15). A
      significant relation was found between medical followup since childhood and fecal
      pseudocontinence. No enema determinants predicted pseudocontinence. CONCLUSIONS:
      Colon enemas are a valuable method in achieving continence. At our center medical
      followup from childhood to adulthood is associated with successful acquisition of
      fecal pseudocontinence.

PMID- 23174230
TI  - Editorial comment.

PMID- 23174231
TI  - Editorial comment.

PMID- 23174232
TI  - Reply by authors.

PMID- 23174233
TI  - Editorial comment.

PMID- 23174234
TI  - Herpes simplex virus vector mediated gene therapy of tumor necrosis factor-alpha
      blockade for bladder overactivity and nociception in rats.
AB  - PURPOSE: We examined the effects of tumor necrosis factor-alpha blockade on
      bladder overactivity and nociception using replication defective HSV vectors
      expressing tumor necrosis factor-alpha soluble receptor. MATERIALS AND METHODS:
      HSV vectors expressing tumor necrosis factor-alpha soluble receptor or beta
      galactosidase/green fluorescent protein as the control were injected into the
      bladder wall of female Sprague-Dawley(r) rats. Green fluorescent protein was
      observed with fluorescent microscopy in the bladder and L6 dorsal root ganglia.
      mRNA and protein expression of tumor necrosis factor-alpha, and interleukin-1beta
      and 6 as well as myeloperoxidase activity in the bladder were determined by
      quantitative reverse transcriptase-polymerase chain reaction and enzyme-linked
      immunosorbent assay 4 hours after intravesical resiniferatoxin administration. c
      Fos positive neurons were counted in the L6 spinal dorsal horn. Cystometry and
      behavioral analyses were also performed. RESULTS: Green fluorescent protein
      expression was confirmed in the bladder and L6 dorsal root ganglia.
      Resiniferatoxin administration significantly increased tumor necrosis factor
      alpha mRNA and protein levels in the bladder in controls. Tumor necrosis factor
      alpha mRNA was also increased in the tumor necrosis factor-alpha soluble receptor
      group, although tumor necrosis factor-alpha protein up-regulation was suppressed.
      The up-regulation of interleukin-1beta and 6 mRNA and protein levels, and the
      myeloperoxidase activity seen in controls were suppressed in the tumor necrosis
      factor-alpha soluble receptor group. c-Fos positive cells in the L6 spinal dorsal
      horn were less prominent in the tumor necrosis factor-alpha soluble receptor
      group than in controls. On cystometry the significant decrease in
      intercontraction intervals after resiniferatoxin infusion detected in controls
      was not seen in the tumor necrosis factor-alpha soluble receptor group. On
      behavioral analyses freezing behavior was significantly decreased in the tumor
      necrosis factor-alpha soluble receptor group without affecting licking behavior.
      CONCLUSIONS: HSV vector mediated tumor necrosis factor-alpha blockade gene
      therapy in the bladder and bladder afferent pathways decreases the bladder pain
      and overactivity induced by nociceptive bladder stimuli.

PMID- 23174235
TI  - A3 adenosine receptor mediates apoptosis in in vitro RCC4-VHL human renal cancer
      cells by up-regulating AMID expression.
AB  - PURPOSE: Accumulating studies have shown that extracellular adenosine induces
      apoptosis in various cancer cells via diverse signaling pathways. We sought to
      understand adenosine induced apoptosis in human renal cancer cells and the
      underlying pathway. MATERIALS AND METHODS: RCC4-VHL (European Collection of
      Animal Cell Cultures, Salisbury, United Kingdom), ACHN (Cell Resource Center for
      Biomedical Research, Institute of Development, Aging and Cancer, Tohuku
      University, Aoba-ku, Sendai, Japan) and 786-O (ATCC(r)) human renal cancer cells
      were cultured. MTT assay, TUNEL staining, reverse transcriptase-polymerase chain
      reaction and Western blot were done in cells untransfected and transfected with
      siRNA silencing the A(3) adenosine receptor targeted gene or the AMID targeted
      gene. RESULTS: Adenosine induced apoptosis in all cell types used in a
      concentration (1 to 10 mM) dependent manner. A similar effect was obtained with
      the A(3) adenosine receptor agonist 2-Cl-IB-MECA. Adenosine induced RCC4-VHL cell
      death was inhibited by the A(3) adenosine receptor inhibitor MRS1191 or by
      knocking down A(3) adenosine receptor or AMID. Adenosine up-regulated the
      expression of AMID mRNA and protein in RCC4-VHL cells, which was suppressed by
      A(3) adenosine receptor knockdown. Moreover, adenosine promoted AMID
      translocation from cytosol to nucleus. CONCLUSIONS: Adenosine induces RCC4-VHL
      cell apoptosis by up-regulating AMID expression and accumulating AMID in the
      nucleus via A(3) adenosine receptor.

PMID- 23174236
TI  - Congenital phimosis in patients with and without lichen sclerosus: distinct
      expression patterns of tissue remodeling associated genes.
AB  - PURPOSE: Lichen sclerosus is a potentially important factor in the ongoing debate
      concerning the pathology of persistent congenital phimosis. We assessed the
      molecular differences of congenital phimosis in boys with and without lichen
      sclerosus compared to age matched boys with fully retractable foreskins to gain
      more insight into the pathogenesis of fibrotic remodeling of the prepuce.
      MATERIALS AND METHODS: A total of 150 boys were circumcised in a prospective
      study between 2007 and 2009. Using target gene specific preamplification and
      quantitative real-time polymerase chain reaction based low density arrays, we
      measured the mRNA expression of 45 tissue remodeling associated genes in
      foreskins of boys with absolute phimosis and lichen sclerosus (8 patients) and
      those of an age matched group of boys with phimosis but no lichen sclerosus (8),
      as well as a control group with foreskins without delimitable changes (6).
      Complementary protein expression and inflammatory infiltrates were assessed by
      immunohistochemical analysis. RESULTS: Cellular composition, inflammatory
      infiltrate and microenvironment as seen in histologically proven lichen sclerosis
      differed significantly from the other groups. In particular, lichen sclerosis was
      characterized by over expression of bone morphogenetic protein 2 and its
      corresponding receptor, matrix metalloproteinases 1 and 9 and tissue inhibitor of
      metalloproteinases 1, cytokine chemokine ligands 5 (RANTES) and interleukin 4,
      and transforming growth factor-beta2 and its corresponding receptor. There were
      no major molecular differences between specimens from boys with congenital
      phimosis without signs of lichen sclerosis and controls. CONCLUSIONS: Distinct
      expression patterns of tissue remodeling associated genes are evident in boys
      with congenital phimosis and lichen sclerosis, while congenital phimosis without
      lichen sclerosis represents a physiological condition.

PMID- 23174237
TI  - Pediatric genitourinary injuries in the United States from 2002 to 2010.
AB  - PURPOSE: We describe the epidemiological features of pediatric genitourinary
      injuries, and determine the products and events that may predict an increased
      risk of genitourinary injury during childhood. MATERIALS AND METHODS: The
      National Electronic Injury Surveillance System was queried to identify children
      18 years or younger who sustained genitourinary injuries and presented to
      emergency departments in the United States between 2002 and 2010. Demographics
      and injury characteristics of these children were analyzed. Analyses were
      performed with adjustments for sample weighting and the stratified survey design.
      All data are reported as national estimates along with 95% confidence intervals.
      RESULTS: Based on 10,286 actual cases, an estimated 252,392 children (95% CI
      205,579-299,194) sustained genitourinary injuries during the 9-year study period.
      Children 4 to 7 years old were most frequently injured (36.8% of all injuries),
      followed by those 8 to 11 years old (20.6%). Girls comprised 55% of the injured
      children. The yearly incidence of genitourinary injuries was stable across the
      period studied. The most commonly injured organs were female external genitalia
      (37.7%), penises (21.6%) and testicles (12%). Genitourinary injuries were most
      commonly associated with sporting and exercise equipment (35.7%), furniture
      (15.5%) and clothing items (11.9%). Of the patients 91% were treated at the
      emergency department and discharged home. CONCLUSIONS: Genitourinary injuries in
      children result in approximately 28,000 emergency department visits yearly.
      Efforts should be made to decrease the risk of genitourinary injuries in children
      by promoting the use of protective gear and safer product selection for those at
      greatest risk for injury.

PMID- 23174238
TI  - Pediatric standard and robot-assisted laparoscopic pyeloplasty: a comparative
      single institution study.
AB  - PURPOSE: We report our experience and compare the outcomes between standard and
      robot-assisted laparoscopic pyeloplasty to treat ureteropelvic junction
      obstruction in children. MATERIALS AND METHODS: A retrospective cohort study was
      performed of all children who underwent standard or robot-assisted laparoscopic
      pyeloplasty for ureteropelvic junction obstruction at a single institution from
      October 2007 to January 2012. Indications for surgery included symptomatic
      obstruction and abnormal diuretic renal scan. A successful outcome was defined as
      resolution of clinical symptoms, improvement of hydronephrosis on ultrasound,
      stable ultrasound with resolution of symptoms or improvement of the drainage
      curve on diuretic renal scan. RESULTS: We reviewed 18 patients (median age 8.1
      years) who underwent standard and 46 (8.8 years) who underwent robot-assisted
      laparoscopic pyeloplasty (p = 0.194). Median operative time was 298 minutes
      (range 145 to 387) for standard and 209 minutes (106 to 540) for robot-assisted
      laparoscopic pyeloplasty (p = 0.008). Mean hospitalization was similar between
      the groups (1 day for standard vs 2 days for robot-assisted laparoscopic
      pyeloplasty, p = 0.246). Narcotic use was similar between the groups. Median
      followup was 43 months for standard and 22 months for robot-assisted laparoscopic
      pyeloplasty (p <0.01). Renal ultrasound showed postoperative improvement of
      hydronephrosis in 85% and stable disease in 15% of patients following robot
      assisted laparoscopic pyeloplasty, and improvement in 89.5% and stable disease in
      10.5% after standard laparoscopic pyeloplasty. Symptoms resolved in 100% of
      patients (38 of 38) after robot-assisted laparoscopic pyeloplasty and 87.5% of
      patients (7 of 8) after standard laparoscopic pyeloplasty. CONCLUSIONS: Robot
      assisted laparoscopic pyeloplasty and standard laparoscopic pyeloplasty are
      effective techniques to correct ureteropelvic junction obstruction, with similar
      outcomes. Robot-assisted laparoscopic pyeloplasty had a shorter operative time,
      and its success and complication rates are comparable to standard laparoscopic
      pyeloplasty.

PMID- 23174239
TI  - Febrile urinary tract infections after ureteroneocystostomy and subureteral
      injection of dextranomer/hyaluronic acid for vesicoureteral reflux--do choice of
      procedure and success matter?
AB  - PURPOSE: Despite success rates favoring ureteroneocystostomy over subureteral
      injection of dextranomer/hyaluronic acid for correction of vesicoureteral reflux,
      the reported incidence of postoperative febrile urinary tract infection favors
      the latter. We evaluated contemporary treatment cohorts for an association
      between correction of vesicoureteral reflux and risk of postoperative febrile
      urinary tract infection. MATERIALS AND METHODS: We retrospectively reviewed the
      records of 396 consecutive patients who underwent ureteroneocystostomy or
      subureteral injection of dextranomer/hyaluronic acid between 1994 and 2008. Time
      to event multivariate analyses included preoperative grade of vesicoureteral
      reflux and bladder/bowel dysfunction. RESULTS: Of 316 patients meeting study
      criteria 210 underwent ureteroneocystostomy (356 ureters) and 106 underwent
      subureteral injection of dextranomer/hyaluronic acid (167). Median patient age
      was 5.7 years (IQR 3.4 to 8.3). Median followup was 28 months (IQR 8 to 61).
      Ureteral success was significantly greater after ureteroneocystostomy (88%, 314
      of 356 cases) vs subureteral injection of dextranomer/hyaluronic acid (74%, 124
      of 167, p = 0.0001). When controlling for preoperative grade of vesicoureteral
      reflux and bladder/bowel dysfunction, the risk of persistent reflux was 2.8 times
      greater after subureteral injection of dextranomer/hyaluronic acid (95% CI 1.7
      4.7, p <0.0001). The incidence of febrile urinary tract infection did not
      significantly differ between ureteroneocystostomy (8%, 16 of 210 cases) and
      subureteral injection of dextranomer/hyaluronic acid (4%, 4 of 106; HR 1.96, 95%
      CI 0.64-5.9, p = 0.24) even when controlling for preoperative grade of
      vesicoureteral reflux, a predictor of postoperative febrile urinary tract
      infection on multivariate analysis (HR 2.2 per increase in grade, 95% CI 1.3-3.6,
      p = 0.0022). Persistent reflux was not a predictor of postoperative febrile
      urinary tract infection (HR 0.81, 95% CI 0.22-2.9, p = 0.75 for
      ureteroneocystostomy vs HR 1.8, 95% CI 0.2-17.3, p = 0.6 for subureteral
      injection of dextranomer/hyaluronic acid and HR 1.8, 95% CI 0.3-3.3, p = 0.6 for
      both). CONCLUSIONS: The incidence of postoperative febrile urinary tract
      infection may be independent of radiographic procedural success.

PMID- 23174240
TI  - Editorial comment.

PMID- 23174241
TI  - Urinary neurotrophic factors in healthy individuals and patients with overactive
      bladder.
AB  - PURPOSE: We investigated urinary levels of nerve growth factor, brain-derived
      neurotrophic factor and glial cell line-derived neurotrophic factor in healthy
      individuals and patients with overactive bladder. MATERIALS AND METHODS: Urine
      from 40 healthy volunteers, half of them male and half female, was collected in
      the morning, afternoon and evening on 2 occasions 3 months apart. Morning urine
      samples were collected from 37 female naive patients with overactive bladder. A
      total of 24 patients were followed. Urine was collected after a 3-month lifestyle
      intervention and after 3-month antimuscarinic treatment (oxybutynin 10 mg,
      extended release). Urinary nerve growth factor, brain-derived neurotrophic factor
      and glial cell line-derived neurotrophic factor concentrations were measured by
      enzyme-linked immunosorbent assay and normalized to creatinine. Patients
      completed a 7-day bladder diary combined with an urgency severity scale. The
      number of urgency episodes per week was counted. RESULTS: In healthy individuals
      urinary levels of neurotrophic factors were stable. In patients with overactive
      bladder the nerve growth factor-to-creatinine (mean +/- SD 488.5 +/- 591.8 vs
      188.3 +/- 290.2, p = 0.005) and brain-derived neurotrophic factor-to-creatinine
      (mean 628.1 +/- 590.5 vs 110.4 +/- 159.5, p <0.001) ratios were significantly
      higher than in healthy women. No significant differences were found in the glial
      cell line-derived neurotrophic factor-to-creatinine ratio. After lifestyle
      intervention the nerve growth factor-to-creatinine and brain-derived neurotrophic
      factor-to-creatinine ratios decreased to a mean of 319.7 +/- 332.3 and 432.5 +/-
      589.0 (vs baseline p = 0.318 and 0.033, respectively). After antimuscarinic
      treatment the nerve growth factor-to-creatinine and brain-derived neurotrophic
      factor-to-creatinine ratios further decreased to a mean of 179.8 +/- 237.9 and
      146.6 +/- 264.9 (vs baseline p = 0.008 and <0.001, respectively). There was no
      significant variation in the glial cell line-derived neurotrophic factor-to
      creatinine ratio at any time point. The reduction in the number of urgency
      episodes per week correlated with the brain-derived neurotrophic factor-to
      creatinine variation (Pearson product-moment correlation coefficient r = 0.607, p
      = 0.006) but not with the nerve growth factor-to-creatinine ratio (r = 0.396, p =
      0.094). CONCLUSIONS: The urinary nerve growth factor-to-creatinine and brain
      derived neurotrophic factor-to-creatinine ratios are increased in patients with
      overactive bladder. These findings may have pathophysiological and clinical
      implications.

PMID- 23174242
TI  - A rationale for procedure selection to repair female urethral stricture
      associated with urethrovaginal fistulas.
AB  - PURPOSE: We investigated a rationale for procedure selection to repair female
      urethral stricture associated with urethrovaginal fistula. We compared the
      outcomes of the 5 techniques used. MATERIALS AND METHODS: Between January 1999
      and October 2011, 44 female patients with urethral stricture associated with
      urethrovaginal fistula were treated using a total of 5 techniques. The surgical
      techniques were labial pedicle flap urethroplasty in 24 patients, vulvar flap
      urethroplasty in 3, anterior vaginal flap urethroplasty in 11, end-to-end
      anastomosis in 4 and bladder flap urethroplasty in 2. Supplementary procedures
      were performed in some patients during urethroplasty, including bladder neck
      reshaping for incontinence in 5, intestinal-vaginal fistula repair in 3,
      colpoplasty for island vulvar skin flaps in 3, middle vaginal stricture
      vaginoplasty in 2 and enlargement of the vaginal introitus in 1. RESULTS: Average
      postoperative followup was 42.3 months (range 6 to 140). Urethrovaginal fistula
      recurred in 2 patients because of infection, urethral stricture developed in 1
      and stress incontinence appeared in 1. The other patients voided normally with an
      average maximum urine flow greater than 15 ml per second (range 16.7 to 46). The
      overall anatomical success rate was 93.18% (41 of 44 cases) and the functional
      success rate was 90.91% (40 of 44). CONCLUSIONS: Surgical procedures for treating
      female urethral strictures with urethrovaginal fistulas should be based on
      fistula location, stricture length and vaginal anatomy. A transvaginal approach
      might be optimal if the vagina is wide and easily dilated. Pedicle labial flap
      urethroplasty was a reliable technique for complex strictures.

PMID- 23174243
TI  - Wrap plication of megaureter around normal-sized ureter for complete duplex
      system reimplantations.
AB  - PURPOSE: A duplex collecting system is a common congenital renal tract
      abnormality associated with different clinical problems. We describe our
      experience with ureteral reimplantations of a complete duplex collecting system
      where 1 megaureter needing recalibration and 1 normal-sized ureter coexisted.
      Recalibration of the megaureter was done by wrap plication around the normal
      sized ureter. MATERIALS AND METHODS: Operative logs and case notes were reviewed
      of consecutive children with a complete duplex collecting system treated with
      wrap plication of the megaureter around the normal-sized ureter and
      reimplantation between 1997 and 2010. Reoperation, vesicoureteral reflux and
      obstruction rates were assessed. RESULTS: A total of 25 children underwent wrap
      plication and ureteral reimplantation. Of the cases 19 (76%) were completely
      successful and 6 (24%) needed reoperation. Three children (12%) had persistent
      high grade vesicoureteral reflux, 2 (8%) underwent endoscopic correction and 1
      (4%) underwent repeat reimplantation of the duplex system. Three children (12%)
      had postoperative obstruction and 2 (8%) underwent endoscopic incision of the
      ureteral orifice. In 1 child (4%) a nonfunctioning lower moiety of the kidney
      developed, which was managed by heminephrectomy. CONCLUSIONS: Wrap plication of a
      megaureter around the normal-sized ureter before reimplantation seems to be a
      relatively safe method in the surgical management of children with a complete
      duplex collecting system of the kidney. Sufficient spatulation of the lower pole
      ureter seems to be crucial.

PMID- 23174244
TI  - A comparative study of the efficacy of intralesional verapamil versus normal
      saline injection in a novel Peyronie disease animal model: assessment of
      immunohistopathological changes and erectile function outcome.
AB  - PURPOSE: While intralesional injections improve penile curvature and decrease
      plaque volume, the exact mechanism of action on Peyronie disease is unknown. We
      evaluated penile curvature, immunohistology and erectile function outcomes after
      intralesional injections of verapamil and normal saline in a previously described
      Peyronie disease animal model. MATERIALS AND METHODS: Peyronie plaque was induced
      in 12 adult male rats using an established Peyronie disease animal model. At 4
      weeks the rats were divided into group 1-5 with 0.1 mg/0.1 ml intralesional
      verapamil injected every second day for 2 weeks, group 2-5 with 0.1 ml
      intralesional normal saline injection and group 3-2 that served as controls. At
      weeks 6 and 8 penile pressure was measured and serial immunohistochemical
      staining of penile tissue sections was done. RESULTS: Intralesional injection of
      verapamil and normal saline resulted in macroscopic and microscopic changes to
      penile curvature and Peyronie plaque size. Decreased collagen and elastin fibers
      were measured with a significant reduction in smooth muscle alpha-actin (p
      <0.05). Changes were greater in group 1 than group 2 (p <0.05). Intralesional
      verapamil injection was associated with greater recovery of electrostimulated
      penile pressure, a surrogate of erectile function, than in the saline and control
      groups. CONCLUSIONS: To our knowledge this novel study offers for the first time
      histological evidence of cellular changes and improvement in penile pressure
      studies in rats with Peyronie plaque after intralesional verapamil injection
      therapy in a Peyronie disease animal model.

PMID- 23174247
TI  - Reply by authors.

PMID- 23174246
TI  - The predictive value of a cystocele for concomitant vaginal apical prolapse.
AB  - PURPOSE: Recent studies showing a correlation between descent of the anterior and
      apical vaginal compartments suggest that cystoceles may recur if associated
      apical prolapse is not corrected. However, to date the anatomical relationship of
      apical prolapse with respect to cystocele has been incompletely reported. We
      present the predictive value of a cystocele for clinically significant vaginal
      apical prolapse. MATERIALS AND METHODS: We retrospectively reviewed the records
      of all new patient visits to a urogynecology clinic in a 30-month period. Women
      with a point Ba value of -1 or greater (stage 2 cystocele and above) were
      included in analysis. Predictive values of clinically significant apical
      prolapse, defined as point C -3 or greater, were calculated and stratified by
      cystocele stage. RESULTS: A total of 385 women were included in study. Point Ba
      was the leading edge of prolapse in 83.9% of cases. The position of Ba strongly
      correlated with that of the vaginal apex (Spearman rho = 0.769, p <0.001).
      Overall 59.7% of patients had a point C of -3 or greater. The finding of
      clinically significant apical prolapse increased significantly with increasing Ba
      values. Of patients with stage 2, 3 and 4 cystocele point C was -3 or greater in
      42%, 85% and 100%, respectively. CONCLUSIONS: The finding of stage 2 or greater
      cystocele is highly suggestive of clinically significant apical vaginal descent
      to -3 or greater. Furthermore, as cystocele stage increases, the predictive value
      of apical prolapse also increases. Surgeons contemplating cystocele repair should
      have high suspicion for vaginal apical prolapse and consider concomitant repair.

PMID- 23174248
TI  - The distribution and function of chondroitin sulfate and other sulfated
      glycosaminoglycans in the human bladder and their contribution to the protective
      bladder barrier.
AB  - PURPOSE: Glycosaminoglycan replenishment therapies are commonly applied to treat
      bladder inflammatory conditions such as bladder pain syndrome/interstitial
      cystitis. Although there is evidence that these therapies are clinically
      effective, much is still unknown about the location and function of different
      types of glycosaminoglycans in the bladder. We investigated the location of
      sulfated glycosaminoglycans in the bladder and evaluated their contribution to
      the urothelial barrier. MATERIALS AND METHODS: The location of different
      glycosaminoglycans (heparan sulfate, chondroitin sulfate and dermatan sulfate) in
      human and porcine bladders was investigated with immunofluorescence staining and
      isolating glycosaminoglycans using selective urothelial sampling techniques.
      Barrier function was evaluated with transepithelial electrical resistance
      measurements (Omega.cm(2)) on primary porcine urothelial cell cultures. The
      contribution of different glycosaminoglycans to the bladder barrier was
      investigated with specific glycosaminoglycan digesting enzymes and protamine.
      RESULTS: High glycosaminoglycan concentrations are located around the urothelial
      basal membrane and at the urothelial luminal surface. After removing the
      glycosaminoglycan layer, urothelial permeability increased. Natural recovery of
      the glycosaminoglycan layer takes less than 24 hours. Chondroitin sulfate was the
      only sulfated glycosaminoglycan that was located on the urothelial luminal
      surface and that contributed to urothelial barrier function. CONCLUSIONS: This
      study reveals an important role for chondroitin sulfate in bladder barrier
      function. Therapies aiming at restoring the luminal glycosaminoglycan layer in
      pathological conditions such as bladder pain syndrome/interstitial cystitis are
      based on a sound principle.

PMID- 23174250
TI  - Re: Holmium laser enucleation of the prostate: a modified enucleation technique
      and initial results: Y. G. Gong, D. L. He, M. Z. Wang, X. D. Li, G. D. Zhu, Z. H.
      Zheng, Y. F. Du, L. S. Chang and X. Y. Nan J Urol 2012; 187: 1336-1340.

PMID- 23174249
TI  - CpG island hypermethylation frequently silences FILIP1L isoform 2 expression in
      prostate cancer.
AB  - PURPOSE: Senescence related regulatory pathways serve as barriers to cancer
      immortalization and progression but they are currently not well defined. FILIP1L
      is a growth inhibitory gene with multiple isoforms whose expression is increased
      in senescent prostate and prostate cancer cells, and decreased in many cancers.
      We investigated whether DNA methylation regulates FILIP1L in senescence and in
      prostate cancer development. MATERIALS AND METHODS: FILIP1L mRNA expression was
      assessed in prostate cancer and associated normal prostate tissues using
      quantitative polymerase chain reaction. A tissue microarray was constructed using
      95 prostate cancer specimens and 45 benign prostate specimens. VectraTM imaging
      was used to quantitate nuclear and cytoplasmic FILIP1L protein expression.
      Bisulfite sequencing and Pyrosequencing(r) were used to assess methylation.
      Prostate cancer cell lines were treated with 2'-deoxy-5-azacytidine and mRNA
      expression was assessed. RESULTS: FILIP1L isoform 2 mRNA was increased in
      replicatively senescent human prostate epithelial cells and decreased in prostate
      cancer specimens. We verified a reduction in nuclear FILIP1L protein in prostate
      cancer using tissue microarrays (p = 0.006). A CpG island 5' of the isoform 2
      translational start site was identified that showed hypermethylation in prostate
      cancer cell lines and tumors compared to normal prostate cells and tissues.
      Pyrosequencing confirmed FILIP1L hypermethylation in all 14 tumors compared to
      paired normal tissues (p <0.0001). Isoform 2 expression was induced in prostate
      cancer cell lines using 2'-deoxy-5-azacytidine. CONCLUSIONS: FILIP1L isoform 2 is
      one of the most commonly hypermethylated genes in prostate cancer. It may serve
      as an important marker of prostate cancer. Isoform 2 expression is associated
      with senescence and its down-regulation may represent an early important
      biological event in prostate cancer development.

PMID- 23174251
TI  - Reproductive potential of men with obstructive azoospermia undergoing
      percutaneous sperm retrieval and intracytoplasmic sperm injection according to
      the cause of obstruction.
AB  - PURPOSE: We evaluated the retrieval rates and reproductive outcomes of
      percutaneous sperm retrieval according to the cause of obstructive azoospermia.
      MATERIALS AND METHODS: We retrospectively studied the records of 146 men with
      obstructive azoospermia who underwent sperm retrieval for intracytoplasmic sperm
      injection. Patients were grouped by the cause of obstruction, including 32 with
      congenital bilateral absence of the vas deferens, 59 with vasectomy and 55 with
      obstruction due to post-infection disease. Sperm were retrieved percutaneously
      from the epididymis or testis. We compared retrieval rates and intracytoplasmic
      sperm injection outcomes, including neonatal results, in the groups of men with
      obstructive azoospermia. RESULTS: The success of sperm retrieval was similar
      among the etiology groups, including 100% for congenital bilateral absence of the
      vas deferens, 96.6% for vasectomy and 96.3% for previous infection. Significantly
      fewer men in the congenital bilateral absence of the vas deferens group needed
      testicular aspiration compared to those in the post-infection and vasectomy
      groups (3.1% vs 23.6% and 30.5%, respectively, p <0.001). Sperm cryopreservation
      was possible in 26.7% of the cases and did not significantly differ among the
      groups. Live birth rates after sperm injection were similar in the congenital
      (34.4%), vasectomy (32.2%) and previous infection (36.4%) groups. Birth
      parameters, prematurity and low birth weight rates were comparable among the
      groups. CONCLUSIONS: Percutaneous sperm retrieval is an effective method to
      retrieve sperm in men with obstructive azoospermia irrespective of the cause of
      obstruction. The chance of achieving a live birth and the profile of neonates
      born after sperm injection do not seem to be related to the cause of obstruction.

PMID- 23174252
TI  - Long-term satisfaction and predictors of use of intracorporeal injections for
      post-prostatectomy erectile dysfunction.
AB  - PURPOSE: Intracorporeal injections have low use rates and high discontinuation
      rates. We examined factors associated with intracorporeal injection use, long
      term satisfaction with intracorporeal injection and reasons for discontinuation
      in men treated with radical prostatectomy. MATERIALS AND METHODS: Between October
      2000 and September 2003, 731 men who underwent open radical retropubic
      prostatectomy were enrolled in a prospective outcomes study. The 8-year followup
      evaluation included the UCLA-PCI, and a survey capturing intracorporeal injection
      use, satisfaction and reasons for discontinuation. Logistic regression was used
      to determine associations between intracorporeal injection use and preoperative
      variables. RESULTS: The 8-year self-assessment was completed by 368 (50.4%) men.
      Of these men 140 (38%) indicated prior or current intracorporeal injection use,
      with only 34 using intracorporeal injection at 8 years. Overall, 44% of the men
      were satisfied with intracorporeal injections. Reasons for discontinuation
      included dislike (47%), pain (33%), return of erection (19%), inefficacy (14%)
      and no partner (6%). Men trying intracorporeal injections had greater
      preoperative UCLA-PCI sexual function scores (75.2 vs 65.62, p = 0.00005) as well
      as greater decreases in this score at 3 months (p = 0.0002) and 2 years (p =
      0.003). Higher preoperative sexual function scores were independently associated
      with the use of intracorporeal injections in a model adjusted for age, marital
      status, nerve sparing status and body mass index (OR 1.021, 95% CI 1.008-1.035).
      CONCLUSIONS: Men pursuing intracorporeal injections have better baseline erectile
      function and experience greater deterioration in erectile function during the
      early postoperative period. Despite the high efficacy of injections, many men
      discontinue intracorporeal injections due to dislike or discomfort. Satisfaction
      rates for intracorporeal injections indicate their long-term role in restoring
      sexual function in men with post-prostatectomy erectile dysfunction.

PMID- 23174253
TI  - Laparoendoscopic single site varicocele ligation: comparison of testicular artery
      and lymphatic preservation versus complete testicular vessel ligation.
AB  - PURPOSE: We compared postoperative outcomes in patients treated with
      laparoendoscopic single site varicocele ligation with or without testicular
      artery and lymphatic preservation. MATERIALS AND METHODS: A total of 80 patients
      with left varicocele were randomly divided into 2 groups and treated with
      laparoendoscopic single site varicocele ligation with preservation of the
      testicular artery and lymphatics (40 in group 1) or complete ligation of the
      testicular vessels and lymphatics (40 in group 2). Operative time, hospital stay,
      return to normal activity, postoperative visual analog scale pain scores and
      complications were analyzed. In patients with subfertility preoperative and 3
      month postoperative semen analyses were performed. In patients with scrotal pain
      preoperative and 12-month postoperative visual analog scale pain scores were
      analyzed. RESULTS: A total of 35 patients per group completed the study. Hospital
      stay, return to normal activity and postoperative pain scores did not differ
      between the groups. No major complications were observed. Mean +/- SD operative
      time was 60.7 +/- 10.7 and 48.6 +/- 6.0 minutes in groups 1 and 2, respectively
      (p <0.001). Patients with subfertility, including 22 in group 1 and 21 in group
      2, showed improved semen parameters 3 months postoperatively but postoperative
      values did not differ between the groups. The 17 patients in each group with
      scrotal pain showed decreased pain scores 12 months postoperatively with no
      difference between the groups. CONCLUSIONS: Laparoendoscopic single site
      varicocele ligation is feasible. No differences in postoperative outcomes and
      complications were observed when preserving or not preserving the testicular
      artery and lymphatics.

PMID- 23174254
TI  - Reply by authors.

PMID- 23174255
TI  - Reply by authors.

PMID- 23174256
TI  - A prospective, randomized clinical trial comparing plasmakinetic resection of the
      prostate with holmium laser enucleation of the prostate based on a 2-year
      followup.
AB  - PURPOSE: We compared plasmakinetic resection with holmium laser enucleation of
      the prostate for the treatment of benign prostatic hyperplasia by analyzing 2
      year followup data from a prospective randomized clinical trial. MATERIALS AND
      METHODS: A total of 280 patients were randomly treated with plasmakinetic
      resection or holmium laser enucleation of the prostate. Perioperative and
      postoperative outcome data were obtained during a 2-year followup. RESULTS: No
      significant differences between the 2 surgical groups were observed in the
      preoperative data. Both groups displayed significant improvements after surgery.
      However, we identified no significant differences between the 2 groups in the 2
      year followup data for I-PSS (International Prostate Symptom Score), quality of
      life scores or maximum flow rate values. Patients in the holmium laser
      enucleation group displayed a lower risk of hemorrhage, shorter bladder
      irrigation and catheter times, and shorter hospital stays. A larger amount of
      prostate tissue was retrieved in the holmium laser enucleation group, but the
      operation time was longer for this group than for the plasmakinetic resection
      group. CONCLUSIONS: Plasmakinetic resection and holmium laser enucleation of the
      prostate are effective and safe treatments for benign prostatic hyperplasia.
      Holmium laser enucleation of the prostate can be applied to prostates of all
      sizes, and involves less risk of hemorrhage, decreased bladder irrigation and
      catheter times, as well as reduced hospital stay. Thus, we believe holmium laser
      enucleation of the prostate should be proposed as a potential new gold standard
      surgical therapy instead of transurethral resection of the prostate for patients
      with benign prostatic hyperplasia.

PMID- 23174257
TI  - Critical review of existing patient reported outcome measures after male anterior
      urethroplasty.
AB  - PURPOSE: Male urethral stricture disease can be recurrent and debilitating. The
      aim of any intervention is to allow men to return to a normal state of voiding
      while maintaining a strong quality of life. A systematic review of the literature
      was conducted to assess for the use of patient reported outcome instruments after
      male anterior urethroplasty. MATERIALS AND METHODS: A review of PubMed(r) was
      conducted to identify studies that used a patient reported outcome measure to
      assess patient outcome after open surgical correction of male strictures.
      Preference was given to studies that used an instrument in the preoperative and
      postoperative setting. However, use of an outcome measure solely in the
      postoperative setting was also accepted. After article selection, the 8
      attributes recommended by the Scientific Advisory Committee were used to analyze
      the measurement properties of each patient reported outcome measure. RESULTS: A
      total of 15 studies were identified that included an instrument to assess
      patients with anterior urethral strictures. The studies used differing
      instruments to assess anterior urethral strictures in a nonuniform manner. Four
      studies used a lower urinary tract symptoms instrument, 8 used a
      sexual/ejaculatory dysfunction instrument, and 3 used a lower urinary tract
      symptoms and sexual/ejaculatory function instrument. There was only 1 report that
      described the development of a urethroplasty specific patient reported outcome
      instrument. CONCLUSIONS: Continued effort is necessary to develop a powerful
      instrument to assess patient reported outcomes after male urethroplasty. The
      importance of patient perspective is vital to understanding the success of open
      urethral reconstruction.

PMID- 23174258
TI  - Changes in urine parameters after desert exposure: assessment of stone risk in
      United States Marines transiently exposed to a desert environment.
AB  - PURPOSE: Living in a desert environment has been associated with a higher
      incidence of kidney stone formation, likely because of concentrated urine output,
      higher production of vitamin D and genetic predisposition. We determined the
      changes in urinary parameters after a group of United States Marines temporarily
      transitioned from a temperate environment to a desert environment. MATERIALS AND
      METHODS: A total of 50 Marines completed a questionnaire and performed 3, 24-hour
      urine collections before mobilization to the desert, after 30 days in the desert
      and 2 weeks after returning from the desert. RESULTS: Daily urine output
      decreased 68% to 0.52 L despite marked increased fluid intake (17 L per day).
      Total daily urinary excretion of calcium, uric acid, sodium, magnesium and
      potassium in the desert decreased by 70%, 41%, 53%, 22% and 36%, respectively.
      Urinary pH decreased from 6.1 to 5.6 while in the desert, and citrate and oxalate
      had minimal changes. After their return from the desert, apart from a decrease of
      22% in oxalate, there were no statistically significant differences from
      baseline. While in the desert, relative supersaturation risks of uric acid and
      sodium urate were increased 153% and 56%, respectively. Brushite relative
      supersaturation decreased 24%. After their return there was no statistical
      difference from baseline. CONCLUSIONS: Our findings suggest that the kidneys
      preserved water and electrolytes while the Marines were subjected to the desert
      environment. Despite this conservation, relative saturations indicate increased
      risk of stones in healthy men exposed to a desert environment with rapid
      resolution upon return.

PMID- 23174259
TI  - Reply by authors.

PMID- 23174260
TI  - Re: Recovery of urinary function after radical prostatectomy: identification of
      trajectory cluster groups: C. B. Anderson, M. R. Kaufman, M. S. Dietrich, D. A.
      Barocas, S. S. Chang, M. S. Cookson, J. A. Smith, Jr., P. E. Clark and S. D.
      Herrell J Urol 2012; 187: 1346-1351.

PMID- 23174262
TI  - Re: Gender and body mass index as risk factors for bladder perforation during
      primary transurethral resection of bladder tumors: K. Herkommer, C. Hofer, J. E.
      Gschwend, M. Kron and U. Treiber J Urol 2012; 187: 1566-1570.

PMID- 23174261
TI  - Protamine sulfate induced bladder injury protects from distention induced bladder
      pain.
AB  - PURPOSE: Bladder pain is a debilitating symptom of many urological conditions.
      There is no generally effective treatment. Abnormal urothelial turnover is common
      to multiple disease states but the specific components of urothelial injury and
      the resulting molecular signals that lead to bladder pain are unknown. We
      examined mouse models of bladder injury induced by uropathogenic Escherichia
      coli, protamine sulfate (Sigma(r)) and bacterial lipopolysaccharide to identify
      cellular and molecular correlates underlying pain sensitization in response to
      the stimuli. MATERIALS AND METHODS: C57BL/6 female mice (Jackson Laboratory, Bar
      Harbor, Maine) were given intravesicular protamine sulfate, lipopolysaccharide or
      uropathogenic E. coli. The impact of each on nociception was determined by
      measuring the evoked visceromotor response to bladder distention 24 hours after
      inoculation. Levels of pyuria and tissue inflammation were examined by urinary
      cytology and tissue histology. Quantitative polymerase chain reaction and gene
      expression analysis were used to identify injury profiles associated with
      nociception. RESULTS: Protamine sulfate treatment was significantly analgesic
      upon bladder distention. Protamine treated bladders did not show pyuria or
      extensive tissue damage. Protamine injury was associated with a global decrease
      in the expression of inflammation associated genes. In contrast, uropathogenic E.
      coli injury significantly increased the nociceptive response to bladder
      distention. Lipopolysaccharide treatment did not affect nociception. Finally,
      injury induced expression of inflammation associated genes correlated with
      nociceptive responses. CONCLUSIONS: Protamine treatment of the bladder is
      analgesic and tissue protective, and it suppresses the inflammatory cytokine
      expression normally associated with nociception. Also, the injury modalities that
      result in differential tissue response patterns provide an innovative method for
      identifying mediators of visceral pain.

PMID- 23174263
TI  - Re: Interstitial cystitis--is it time to look beyond the bladder? K. M. Peters J
      Urol 2012; 187: 381-382.

PMID- 23174264
TI  - Cost of neuromodulation therapies for overactive bladder: percutaneous tibial
      nerve stimulation versus sacral nerve stimulation.
AB  - PURPOSE: Conservative therapy and antimuscarinic agents are first line therapies
      for overactive bladder. Patients refractory to treatment are candidates for
      neuromodulation therapy. We estimated the costs and cost-effectiveness of
      percutaneous tibial nerve stimulation and sacral nerve stimulation. MATERIALS AND
      METHODS: A Markov model was constructed to simulate the total costs and
      effectiveness of percutaneous tibial and sacral nerve stimulation during 2 years.
      Cost data used average Medicare national physician payments, and ambulatory
      payment classification and diagnosis related group payments for hospital based
      care and office visits. Clinical effectiveness, and the rates of patient
      adherence to treatment and adverse events were estimated by a review of the
      literature. RESULTS: The costs of initial therapy were $1,773 for 12 weekly
      percutaneous tibial nerve stimulation treatments and $1,857 for test sacral nerve
      stimulation. For ongoing therapy the cost of the sacral nerve stimulation
      surgical implant was $22,970. Cumulative discounted 2-year costs were $3,850 for
      percutaneous tibial nerve stimulation and $14,160 for sacral nerve stimulation,
      including those who discontinued therapy. Of the patients 48% and 49%,
      respectively, remained on therapy. The incremental cost-effectiveness ratio was
      $573,000 per additional patient on sacral nerve stimulation. When considering
      only patients who completed initial stimulation successfully, the costs were
      $4,867 and $24,342 for percutaneous tibial and sacral nerve stimulation with 71%
      and 90%, respectively, remaining on therapy for an incremental cost-effectiveness
      ratio of $99,872. CONCLUSIONS: Percutaneous tibial nerve stimulation and sacral
      nerve stimulation are safe, effective neuromodulation therapies for overactive
      bladder. In this economic model percutaneous tibial nerve stimulation had
      substantially lower cost. An additional 1% of patients would remain on therapy at
      2 years if sacral nerve stimulation were used rather than percutaneous tibial
      nerve stimulation but the average cost per additional patient would be more than
      $500,000.

PMID- 23174266
TI  - Beneficial effects of polyphenols on cardiovascular disease.
AB  - In recent years, numerous studies have demonstrated the health benefits of
      polyphenols, and special attention has been paid to their beneficial effects
      against cardiovascular disease, the leading cause of death in the world today.
      Polyphenols present vasodilator effects and are able to improve lipid profiles
      and attenuate the oxidation of low density lipoproteins. In addition, they
      present clear anti-inflammatory effects and can modulate apoptotic processes in
      the vascular endothelium. It has been suggested that most of these effects are a
      consequence of the antioxidant properties of polyphenols, but this idea is not
      completely accepted, and many other mechanisms have been proposed recently to
      explain the health effects of these compounds. In fact, different signaling
      pathways have been linked to polyphenols. This review brings together some recent
      studies which establish the beneficial properties of polyphenols for
      cardiovascular disease and analyzes the mechanisms involved in these properties.

PMID- 23174265
TI  - Cannabinoid agonists increase the interaction between beta-Arrestin 2 and ERK1/2
      and upregulate beta-Arrestin 2 and 5-HT(2A) receptors.
AB  - We have recently reported that selective cannabinoid 2 (CB(2)) receptor agonists
      upregulate 5-HT(2A) receptors by enhancing ERK1/2 signaling in prefrontal cortex
      (PFCx). Increased activity of cortical 5-HT(2A) receptors has been associated
      with several neuropsychiatric disorders such as anxiety and schizophrenia. Here
      we examine the mechanisms involved in this enhanced ERK1/2 activation in rat PFCx
      and in a neuronal cell model. Sprague-Dawley rats treated with a non-selective
      cannabinoid agonist (CP55940, 50MUg/kg, 7 days, i.p.) showed enhanced co
      immunoprecipitation of beta-Arrestin 2 and ERK1/2, enhanced pERK protein levels,
      and enhanced expression of beta-Arrestin 2 mRNA and protein levels in PFCx. In a
      neuronal cell line, we found that selective CB(2) receptor agonists upregulate
      beta-Arrestin 2, an effect that was prevented by selective CB(2) receptor
      antagonist JTE-907 and CB(2) shRNA lentiviral particles. Additionally, inhibition
      of clathrin-mediated endocytosis, ERK1/2, and the AP-1 transcription factor also
      prevented the cannabinoid receptor-induced upregulation of beta-Arrestin 2. Our
      results suggest that sustained activation of CB(2) receptors would enhance beta
      Arrestin 2 expression possibly contributing to its increased interaction with
      ERK1/2, thereby driving the upregulation of 5-HT(2A) receptors. The CB(2)
      receptor-mediated upregulation of beta-Arrestin 2 would be mediated, at least in
      part, by an ERK1/2-dependent activation of AP-1. These data could provide the
      rationale for some of the adverse effects associated with repeated cannabinoid
      exposure and shed light on some CB(2) receptor agonists that could represent an
      alternative therapeutic because of their minimal effect on serotonergic
      neurotransmission.

PMID- 23174267
TI  - Stability of the splay state in networks of pulse-coupled neurons.
AB  - We analytically investigate the stability of splay states in the networks of N
      globally pulse-coupled phase-like models of neurons. We develop a perturbative
      technique which allows determining the Floquet exponents for a generic velocity
      field and implement the method for a given pulse shape. We find that in the case
      of discontinuous velocity fields, the Floquet spectrum scales as 1/N2 and the
      stability is determined by the sign of the jump at the discontinuity. Altogether,
      the form of the spectrum depends on the pulse shape, but it is independent of the
      velocity field.PACS: 05.45.Xt, 84.35.+i, 87.19.lj.

PMID- 23174268
TI  - Community-level effects in edaphic fauna from an abandoned mining area:
      integration with chemical and toxicological lines of evidence.
AB  - As a part of the Ecological Risk Assessment of a deactivated uranium mining area
      (Cunha Baixa), the aim of this study was to assess the drivers of litter
      arthropod community (ecological line of evidence) inhabiting soils with different
      degrees of contamination. Litter arthropods were collected in the mining area
      using a total of 70 pitfall traps, in the spring and autumn of 2004. Unlike
      information previously collected in the chemical and ecotoxicological lines of
      evidence, we found no clear evidence of impacts of soil contamination on the
      edaphic arthropod assemblage. Multivariate analyses were unable to extract
      relevant environmental gradients related to contamination, as most of the sites
      shared the same taxa overall. Given the consistency of the chemical and
      ecotoxicological lines of evidence, we must conclude that the litter arthropod
      assemblage underestimated the impacts of contamination in this abandoned mining
      area. In part, this could be due to the uncertainty caused by confounding factors
      that affect the litter arthropod community in the area. Nevertheless, despite the
      overall lack of responsiveness of the epigeic arthropod community data, a few
      taxa were negatively correlated with metal concentrations (Clubionidae and
      Staphylinidae), while Pseudoscorpionida were associated with the toxicological
      profile of the sites. These evidences suggest that community-level approaches
      with other animal and plant assemblages are necessary to reduce uncertainty
      relatively to the assessment of risks in higher evaluation tiers in the Cunha
      Baixa mine area.

PMID- 23174269
TI  - Effect of silver nanoparticles on Oryza sativa L. and its rhizosphere bacteria.
AB  - Silver nanoparticles (AgNPs) are widely used as antibacterial and antifungal
      agents in agriculture. Nevertheless, these nanoparticles with newborn properties
      pose a potential risk to the environment, Due to contact with crops and bacteria
      that are beneficial to the soil. This study is based on the examination of the
      phytotoxic effects of AgNPs on Oryza sativa L. and some of its rhizosphere
      bacteria, by physiological and biochemical assays. In order to study the complex
      interaction of the AgNPs life expectancy that are mixed with culture medium, the
      incubation time for the fresh mixture, 7, 14 and 21 days old of AgNPs, on the
      seedlings growth was investigated. Results indicated that plant's response to the
      treatment with AgNPs affected on the cell wall, and that with an increase in its
      concentration (up to 60 MUg/mL). The obtained results of transmission electron
      microscopy (TEM) exhibited that those particles not only penetrated the cell
      wall, but they could also damage the cell morphology and its structural features.
      AgNPs treatment up to 30 MUg/mL accelerated root growth and at 60 MUg/mL was able
      to restrict a root's ability to grow. The 30 MUg/mL treatment had significant
      effect on root branching and dry weight. In contrast, shoot growth was more
      susceptible to the effects of AgNPs treatment. The root content for total soluble
      carbohydrates and starch demonstrated that despite stable starch content, total
      soluble carbohydrates showed the tendency to significantly decline in response to
      AgNPs. However, induction of root branching and photosynthetic pigments can
      attributed to AgNPs stress based on evidence from the production of the reactive
      oxygen species (ROS) and local root tissue death. Nine isolates of the genus
      Bacillus selected and identified according to morphological and chemotaxonomic
      methods. The AgNPs treatment revolutionized the populations of bacteria as
      Bacillus thuringiensis SBURR1 was totally eliminated, and Bacillus
      amyloliquefaciens SBURR5 became the most populated one. Images from an electron
      microscope and the leakage of reducing sugars and protein through the bacterial
      membrane, similarly confirmed the "pit" formation mechanism of the AgNPs.
      Moreover the hypothesis from the growth curve study demonstrated that AgNPs may
      damage bacterium cell wall and transform them to protoplasts.

PMID- 23174270
TI  - [Amyloidosis in sub-Saharan Africa].
AB  - Amyloidosis is a protein folding disorder in which normally soluble proteins are
      deposited extracellularly as insoluble fibrils. When stained with Congo red dye,
      it produces apple-green birefringence under polarized light. The main amyloid
      proteins are AL, AA, ATTR and Abeta(2)-M. The incidence of amyloidosis in sub
      Saharan Africa ranges from 0.28 to 0.57% in autopsy series. Secondary AA
      amyloidosis is the most frequent, found in 42 to 66% of amyloidoses. Chronic
      infections, especially tuberculosis, are the main cause. AL amyloidosis is found
      in 21 to 34% of amyloidosis cases, half of them due to myeloma. Other types of
      amyloidosis seem rare, but are probably underdiagnosed. The clinical presentation
      in sub-Saharan Africa is similar to that in Western series. Further experimental
      and clinical studies will allow a better assessment of the characteristics of
      amyloidosis in sub-Saharan Africa.

PMID- 23174271
TI  - Formative evaluation of the feedback component of Children's and Adolescents'
      Nutrition Assessment and Advice on the Web (CANAA-W) among parents of
      schoolchildren.
AB  - OBJECTIVE: The aim of the paper is to describe the formative evaluation of the
      feedback component of an online nutrition tailoring instrument, the Children's
      and Adolescents' Nutrition Assessment and Advice on the Web (CANAA-W), among
      parents of schoolchildren. DESIGN: Parents of pre-primary and primary-school
      children recorded their child's food intake over 3 d with CANAA-W and completed
      the evaluation questionnaire online. A subsample participated in focus group
      discussions. SETTING: Parents completed CANAA-W at home. SUBJECTS: Forty-six
      parents completed the evaluation questionnaire. Seventeen parents participated in
      three focus group discussions. RESULTS: Parents were enthusiastic: the majority
      (81 % or more) found the advice comprehensible, interesting, logical, useful,
      believable, well formulated, correct, personal, relevant, complete, attractive,
      containing enough and not too much information; they indicated that it is helpful
      to improve their children's eating habits and that they intend to use it. The
      qualitative analyses revealed that the respondents appreciated the confrontation
      with their child's diet and the visualization (i.e. traffic light colours,
      pictograms, food models, diagrams). The length of the feedback was rather a
      drawback, but it was useful nevertheless. CONCLUSIONS: CANAA-W was well received
      by the parents; the scores on the feasibility questionnaire were high and the
      qualitative analyses showed that the confrontation with their child's diet, and
      attractive visualization of the most relevant feedback linked to more elaborated
      optional feedback, were well appreciated. The major challenge will be to convince
      parents who are less interested in food habits and less computer-literate to
      participate in this type of study.

PMID- 23174272
TI  - Acquisition of English grammatical morphology by internationally adopted children
      from China.
AB  - Acquisition of English grammatical morphology was examined in five
      internationally adopted (IA) children from China (aged 0;10-1;1 at adoption)
      during the first three years' exposure to English to determine whether
      acquisition patterns were characteristic of child second language (L2) learners
      or monolingual first language (L1) learners. Results from spontaneous and
      elicited speech showed that IA children acquired grammatical morphemes similarly
      to L1 learners; namely, (1) non-tense-marking morphemes were acquired earlier
      than tense-marking morphemes; (2) BE was acquired in synchrony with other tense
      marking morphemes; and (3) a high percentage of omission errors and a low
      percentage of commission errors were observed.

PMID- 23174273
TI  - How common are lymph node metastases in patients with Barrett's esophagus
      complicated by high-grade dysplasia or intramucosal cancer?

PMID- 23174274
TI  - Liver stiffness measurement: simplicity is prerequisite for reliability.

PMID- 23174276
TI  - IBS bowel habits and associated symptoms: forming a clearer picture.

PMID- 23174277
TI  - MLVA-16 loci panel on Brucella spp. using multiplex PCR and multicolor capillary
      electrophoresis.
AB  - The Multi Locus Variable Number Tandem Repeat Analysis 16 loci panel (MLVA-16),
      involving singleplex PCRs and agarose gel electrophoresis, is the standard
      genotyping method for Brucella spp., used also for the Brucella international
      online database. We describe an alternative, reliable, high-throughput MLVA-16
      protocol using multiplex PCRs and multicolor capillary electrophoresis.

PMID- 23174279
TI  - A variable structure fuzzy neural network model of squamous dysplasia and
      esophageal squamous cell carcinoma based on a global chaotic optimization
      algorithm.
AB  - Identification of squamous dysplasia and esophageal squamous cell carcinoma
      (ESCC) is of great importance in prevention of cancer incidence. Computer aided
      algorithms can be very useful for identification of people with higher risks of
      squamous dysplasia, and ESCC. Such method can limit the clinical screenings to
      people with higher risks. Different regression methods have been used to predict
      ESCC and dysplasia. In this paper, a Fuzzy Neural Network (FNN) model is selected
      for ESCC and dysplasia prediction. The inputs to the classifier are the risk
      factors. Since the relation between risk factors in the tumor system has a
      complex nonlinear behavior, in comparison to most of ordinary data, the cost
      function of its model can have more local optimums. Thus the need for global
      optimization methods is more highlighted. The proposed method in this paper is a
      Chaotic Optimization Algorithm (COA) proceeding by the common Error Back
      Propagation (EBP) local method. Since the model has many parameters, we use a
      strategy to reduce the dependency among parameters caused by the chaotic series
      generator. This dependency was not considered in the previous COA methods. The
      algorithm is compared with logistic regression model as the latest successful
      methods of ESCC and dysplasia prediction. The results represent a more precise
      prediction with less mean and variance of error.

PMID- 23174278
TI  - A polyphyletic model for the origin of tRNAs has more support than a monophyletic
      model.
AB  - The monophyletic and polyphyletic origins of tRNAs are compared. The monophyletic
      hypothesis of the origin of the tRNA molecule would turn out to be strictly true
      only if a universal tRNA, possessing a number of anticodons with which to read
      primitive mRNAs, was present at the Last Universal Common Ancestor (LUCA) stage.
      On the other hand, whether a tRNA precursor less complex than it - for instance a
      hairpin - was present at the LUCA stage, then one should imperatively predict a
      phase of evolutionary convergence towards the cloverleaf structure typical of
      tRNAs, equivalent to a polyphyletic origin, also in presence of a real
      monophyletic origin. Thus, the monophyletic hypothesis is not able to eliminate
      the main trouble inherent in the evolutionary convergence, for which it is
      usually invoked. Arguments opposed to the existence of a universal tRNA and in
      favour of less complex precursors to tRNA, combined with the existence of two
      different classes of tRNAs, and, in particular, tyrosine tRNA being a class II
      tRNA in the bacterial domain but a class I tRNA in the eukaryal and archaeal
      domains, support a polyphyletic origin of tRNA molecules. It might have been the
      main path for the evolution of tRNAs, also because a polyphyletic origin of tRNA
      genes has been corroborated.

PMID- 23174280
TI  - Designing a robust minimum variance controller using discrete slide mode
      controller approach.
AB  - Designing minimum variance controllers (MVC) for nonlinear systems is confronted
      with many difficulties. The methods able to identify MIMO nonlinear systems are
      scarce. Harsh control signals produced by MVC are among other disadvantages of
      this controller. Besides, MVC is not a robust controller. In this article, the
      Vector ARX (VARX) model is used for simultaneously modeling the system and
      disturbance in order to tackle these disadvantages. For ensuring the robustness
      of the control loop, the discrete slide mode controller design approach is used
      in designing MVC and generalized MVC (GMVC). The proposed method for controller
      design is tested on a nonlinear experimental Four-Tank benchmark process and is
      compared with nonlinear MVCs designed by neural networks. In spite of the
      simplicity of designing GMVCs for the VARX models with uncertainty, the results
      show that the proposed method is accurate and implementable.

PMID- 23174281
TI  - Variability-specific differential gene expression across reproductive stages in
      sows.
AB  - Differential gene expression analyses typically focus on departures across
      mathematical expectations (i.e. mean) from two or more groups of microarrays,
      without considering alternative patterns of departure. Nevertheless, recent
      studies in humans and great apes have suggested that differential gene expression
      could also be characterized in terms of heterogeneous dispersion patterns. This
      must be viewed as a very interesting genetic phenomenon clearly linked to the
      regulation mechanisms of gene transcription. Unfortunately, we completely lack
      information about the incidence and relevance of dispersion-specific differential
      gene expression in livestock species, although a specific Bayes factor (BF) for
      testing this kind of differential gene expression (i.e. within-probe
      heteroskedasticity) has been recently developed. Within this context, our main
      objective was to characterize the incidence of dispersion-specific differential
      gene expression in pigs and, if possible, providing the first evidence of this
      phenomenon in a livestock species. We evaluated dispersion-specific differential
      gene expression on ovary, uterus and hypophysis samples from 22 F2 Iberian *
      Meishan sows, where a total of 15,252 probes were interrogated. For each tissue,
      heteroskedasticity of probe-specific residual variances was evaluated by three
      pairwise comparisons involving three physiological stages, that is, heat, 15 days
      of pregnancy and 45 days of pregnancy. Between 2.9% and 37.4% of the analyzed
      probes provided statistical evidence of within-tissue across-physiological stages
      dispersion-specific differential gene expression (BF >1), and between 0.1% and
      3.0% of them reported decisive evidence (BF >100). It is important to highlight
      that <8% of the heteroskedastic probes were also linked to differential gene
      expression in terms of departures among the probe-specific mathematical
      expectation of each physiological stage. This discarded the disturbance of scale
      effects in a high percentage of probes and suggested that probe-specific
      heteroskedasticity must be viewed as an independent phenomenon within the context
      of differential gene expression. As a whole, our results report a remarkable
      incidence of dispersion-specific differential gene expression across the whole
      genome of the pig, establishing a very interesting starting point for further
      studies focused on deciphering the genetic mechanisms underlying
      heteroskedasticity.

PMID- 23174282
TI  - Functional expression of a foreign gene in Aspergillus oryzae producing new
      pyrone compounds.
AB  - Fungi from the genus Xylaria produce a wide range of polyketides with diverse
      structures, which provide important sources for pharmaceutical agents. At least
      seven polyketide synthase (PKS) genes, including pksmt, were found in Xylaria sp.
      BCC 1067. The multifunctional enzyme pksmt contains the following catalytic
      motifs: beta-ketosynthase (KS), acyltransferase (AT), dehydratase (DH),
      methyltransferase (MT), enoylreductase (ER), ketoreductase (KR), and acyl carrier
      region (ACP). The presence of multiple domains indicated that pksmt was an
      iterative type I highly-reduced-type PKS gene. To identify the gene function,
      pksmt was fused with a gene encoding green fluorescent protein (GFP) and
      introduced into a surrogate host, Aspergillus oryzae, and expressed under the
      control of a constitutive gpdA promoter. In the transformant, the pksmt gene was
      functionally expressed and translated as detected by a green fluorescence signal.
      This transformant produced two new 2-pyrone compounds, 4-(hydroxymethyl)-5,6
      dihydro-pyran-2-one and 5-hydroxy-4-methyl-5,6-dihydro-pyran-2-one, as well as a
      previously identified 4-methyl-5,6-dihydro-pyran-2-one. Our results suggested
      that pksmt from Xylaria sp. BCC 1067 represents a family of fungal PKSs that can
      synthesize 2-pyrone-containing compounds.

PMID- 23174283
TI  - Biofuels development and the policy regime.
AB  - Any major change to the energy order is certain to provoke both positive and
      negative societal responses. The current wave of biofuels development ignited
      controversies that have re-shaped the thinking about their future development.
      Mistakes were made in the early support for road transport biofuels in
      Organisation for Economic Co-operation and Development (OECD) countries. This
      article examines some of the policies that shaped the early development of
      biofuels and looks to the future.

PMID- 23174284
TI  - Reply: Crystal P. Tyler, for the ELGAN Study Authors.

PMID- 23174286
TI  - Discussion: 'Metabolomic prediction of late-onset preeclampsia', by Bahado-Singh
      et al.

PMID- 23174285
TI  - Associations between vaginal bacteria and levels of vaginal defensins in pregnant
      women.
AB  - OBJECTIVE: We evaluated vaginal defensin concentrations and levels of bacterial
      vaginosis-associated bacterial species in pregnant women. STUDY DESIGN: Self
      collected vaginal swabs from 2 visits during pregnancy were tested with
      quantitative polymerase chain reaction for 9 bacterial species. Beta defensins 2
      3 and alpha defensins 1-3 were measured by enzyme-linked immunosorbent assay.
      RESULTS: Our 126 participants were primarily African American (60%), had a mean
      gestational age at enrollment of 10 +/- 3 weeks and at follow-up visit of 25 +/-
      6 weeks. At enrollment, the prevalence of bacterial vaginosis was 74% (94/126
      women), which decreased to 60% (75/126 specimens) at follow-up visit. At
      enrollment, beta defensin 3 concentrations were significantly lower in women with
      bacterial vaginosis (2.64 +/- 0.91 vs 3.25 +/- 0.99 log(10) pg/mL; P = .003).
      Higher concentrations of Atopobium vaginae, bacterial vaginosis-associated
      bacteria1 and 2 were associated with significantly lower concentrations of beta
      defensin 3 (P < .01). CONCLUSION: Bacterial vaginosis was associated with lower
      vaginal concentrations of beta defensin 3, but not beta defensin 2 or alpha
      defensins 1-3, in pregnant women.

PMID- 23174287
TI  - Brain damage and maternal medication.

PMID- 23174288
TI  - The use of aspirin during pregnancy.

PMID- 23174289
TI  - Comparison of cervical cancer screening strategies incorporating different
      combinations of cytology, HPV testing, and genotyping for HPV 16/18: results from
      the ATHENA HPV study.
AB  - OBJECTIVE: The objective of the study was to compare 9 cervical cancer screening
      strategies to the current screening standard (cytology with human papillomavirus
      [HPV] triage of atypical squamous cells of undetermined significance) for the
      detection of high-grade cervical disease. STUDY DESIGN: Women (n = 34,254) aged
      30 years or older from the Addressing the Need for Advanced HPV Diagnostics
      (ATHENA) study underwent screening with cytology and HPV testing with
      simultaneous HPV16/18 genotyping; those with atypical squamous cells of
      undetermined significance cytology or greater or HPV-positive status were
      referred for colposcopy. RESULTS: In general, screening strategies that offered
      greater sensitivity also required more referral to colposcopy. HPV testing was
      more sensitive than cytology for detection of cervical intraepithelial neoplasia
      grade 2 or greater, but strategies that depended on cytology for triage of HPV
      positive women decreased this sensitivity. Various strategies of cotesting with
      cytology increased sensitivity but did so by increasing testing. Strategies that
      included integrated HPV16/18 testing provided more efficient referral to
      colposcopy. CONCLUSION: Strategies that maximize detection of women at greatest
      risk of cervical intraepithelial neoplasia grade 3 or greater by immediate
      referral to colposcopy, with follow-up testing of women at intermediate risk,
      maximize the benefits of cervical cancer screening while decreasing the potential
      harm. Incorporating screening with HPV and triage of HPV-positive women by a
      combination of genotyping for HPV16/18 and cytology provided a good balance
      between maximizing sensitivity (benefit) and specificity by limiting the number
      of colposcopies (potential harm).

PMID- 23174290
TI  - Monopolin.

PMID- 23174291
TI  - Place, space and memory cells.

PMID- 23174292
TI  - 21 years of shelf life between discovery and description of new species.

PMID- 23174293
TI  - Sleep biology: tuning in while tuned out.
AB  - The barrel cortex and whisker thalamus preferentially respond to whisker
      movements during REM sleep in infant rats. Understanding why the brain tunes into
      sensory signals while it's tuned out in sleep may provide clues about the
      functions of REM sleep.

PMID- 23174294
TI  - Aging: evolution of life span revisited.
AB  - A new study reports that high rates of extrinsic mortality can lead to the
      evolution of a longer life - a pattern opposite to that expected under the
      classic predictions of the evolutionary theory of aging.

PMID- 23174295
TI  - Dopamine: on the threshold of sleep.
AB  - A new study examining the neural circuitry regulating sleep in Drosophila has
      identified a pair of dopamine neurons that signal to the fan-shaped body to
      suppress sleep. These neurons are separate from the dopamine neurons that
      regulate motivation, memory, and feeding, suggesting that independent populations
      of dopamine neurons regulate distinct behaviors.

PMID- 23174296
TI  - Histones: sequestered by Jabba in fatty storehouse.
AB  - A paper in this issue shows that histones H2a and H2b are stored in lipid
      droplets in Drosophila embryos complexed with the protein Jabba. In Jabba mutant
      embryos, histones H2a and H2b are degraded but embryos survive by translating
      stored histone mRNA.

PMID- 23174298
TI  - Evolution: cichlid models on the runaway to speciation.
AB  - Rapid speciation has fascinated biologists for a long time. A recent study shows
      that ecological opportunity and sex-biased color differences increase the
      likelihood of speciation in African cichlid fishes.

PMID- 23174297
TI  - Sexual attraction: sex-specific wiring of neural circuitry.
AB  - Two recent studies describe mechanisms by which sexually dimorphic responses to
      pheromones in the nematode worm Caenorhabditis elegans are driven by differences
      in the balance of neural circuits that control attraction and repulsion
      behaviors.

PMID- 23174299
TI  - Cell biology: cohesin ring exit gate revealed.
AB  - A multiprotein complex called cohesin mediates sister chromatid cohesion by
      entrapping sister DNAs into a tripartite ring. Recent studies show that Wapl
      opens the newly identified DNA exit gate of the cohesin ring, only when Smc3 is
      deacetylated, and that mutations in human Smc3 deacetylase cause a developmental
      disorder.

PMID- 23174300
TI  - Transcription: base J blocks the way.
AB  - How do cells stop transcribing RNA Polymerase II to promote proper gene
      expression and prevent transcriptional havoc in the genome? In the case of
      Leishmania, a uniquely modified DNA base blocks RNA Polymerase II and suggests an
      interesting new model for transcription termination.

PMID- 23174301
TI  - Organelle biogenesis: en BLOC exchange for RAB32 and RAB38.
AB  - Prominent subtypes of the genetic disorder Hermansky-Pudlak syndrome result from
      defects in a mysterious protein complex, BLOC-3. New work identifies BLOC-3 as a
      guanine nucleotide exchange factor for two RAB GTPases previously implicated in
      lysosome-related organelle biogenesis.

PMID- 23174302
TI  - The spindle assembly checkpoint.
AB  - During mitosis and meiosis, the spindle assembly checkpoint acts to maintain
      genome stability by delaying cell division until accurate chromosome segregation
      can be guaranteed. Accuracy requires that chromosomes become correctly attached
      to the microtubule spindle apparatus via their kinetochores. When not correctly
      attached to the spindle, kinetochores activate the spindle assembly checkpoint
      network, which in turn blocks cell cycle progression. Once all kinetochores
      become stably attached to the spindle, the checkpoint is inactivated, which
      alleviates the cell cycle block and thus allows chromosome segregation and cell
      division to proceed. Here we review recent progress in our understanding of how
      the checkpoint signal is generated, how it blocks cell cycle progression and how
      it is extinguished.

PMID- 23174303
TI  - Endovascular treatment of symptomatic intracranial atheromatous stenosis: a
      single center study of 21 consecutive cases.
AB  - OBJECTIVES: This retrospective single-center study evaluated the technical
      success as well as the periprocedural and long-term complications of angioplasty
      with stenting of symptomatic intracranial atheromatous stenosis. PATIENTS AND
      METHODS: From January 2005 to December 2010, 21 patients were treated by
      angioplasty with stent implantation for symptomatic atheromatous intracranial
      stenosis greater or equal to 50% at least 7 days after a stroke. RESULTS: The
      median population age was 65 years (range: 41-88 years), and 76% (16/21) of the
      candidates had a history of transient ischemic attack (TIA) or stroke before the
      event qualifying them for an endovascular procedure. In addition, 86% (18/21)
      were taking antithrombotic medication at the time of the qualifying event.
      Technical success was obtained in all cases. The periprocedural stroke or death
      rate was 9.5% (2/21), and there was no other stroke or death after 30 days during
      the mean follow-up of 1.4 years. CONCLUSION: Endovascular treatment of
      symptomatic intracranial atherothrombotic stenosis can lead to severe
      complications, particularly during the periprocedural period, but it also
      represents the only alternative treatment for patients who fail with medical
      therapy. Future studies need to focus on improvement of periprocedural
      complications. Essentially, this should include more rigorous selection of
      candidates as well as a better understanding of the pathophysiological
      mechanism(s) of the ischemic phenomenon related to stenosis.

PMID- 23174304
TI  - Chemical evolution of Macondo crude oil during laboratory degradation as
      characterized by fluorescence EEMs and hydrocarbon composition.
AB  - The fluorescence EEM technique, PARAFAC modeling, and hydrocarbon composition
      were used to characterize oil components and to examine the chemical evolution
      and degradation pathways of Macondo crude oil under controlled laboratory
      conditions. Three major fluorescent oil components were identified, with Ex/Em
      maxima at 226/328, 262/315, and 244/366 nm, respectively. An average degradation
      half-life of ~20 d was determined for the oil components based on fluorescence
      EEM and hydrocarbon composition measurements, showing a dynamic chemical
      evolution and transformation of the oil during degradation. Dispersants appeared
      to change the chemical characteristics of oil, to shift the fluorescence EEM
      spectra, and to enhance the degradation of low-molecular-weight hydrocarbons.
      Photochemical degradation played a dominant role in the transformation of oil
      components, likely an effective degradation pathway of oil in the water column.
      Results from laboratory experiments should facilitate the interpretation of field
      data and provide insights for understanding the fate and transport of oil
      components in the Gulf of Mexico.

PMID- 23174305
TI  - Physical dynamics controlling variability in nearshore fecal pollution: fecal
      indicator bacteria as passive particles.
AB  - We present results from a 5-h field program (HB06) that took place at
      California's Huntington State Beach. We assessed the importance of physical
      dynamics in controlling fecal indicator bacteria (FIB) concentrations during HB06
      using an individual based model including alongshore advection and cross-shore
      variable horizontal diffusion. The model was parameterized with physical (waves
      and currents) and bacterial (Escherichia coli and Enterococcus) observations made
      during HB06. The model captured surfzone FIB dynamics well (average surfzone
      model skill: 0.84 {E. coli} and 0.52 {Enterococcus}), but fell short of capturing
      offshore FIB dynamics. Our analyses support the hypothesis that surfzone FIB
      variability during HB06 was a consequence of southward advection and diffusion of
      a patch of FIB originating north of the study area. Offshore FIB may have
      originated from a different, southern, source. Mortality may account for some of
      the offshore variability not explained by the physical model.

PMID- 23174306
TI  - Eutrophication, risk management and sustainability. The perceptions of different
      stakeholders in the northern Baltic Sea.
AB  - The environmental condition of the Baltic Sea is not only of concern for natural
      scientists. The awareness of the deteriorating state of the ecosystem has become
      an issue of interdisciplinary interest, and the amount of organizations with the
      marine environment and ecosystem health on the agenda is large. To present
      holistic and sustainable solutions and results of the actions taken, an active
      cooperation between all stakeholder groups and levels are needed. How different
      stakeholders in the northern Baltic Sea perceive the structures and assessments
      of the eutrophication were analyzed by semi-structured interviews with 17
      stakeholders representing authorities, scientists, NGOs and national interest
      organizations. The focus was the view of the governance structures, risk
      assessment, management and communication. There was an overall consensus that
      eutrophication is a serious problem. Still variations in the opinions both within
      and between the stakeholder groups were seen. The scientists were most divergent
      from the rest.

PMID- 23174307
TI  - Multiscale analysis of slow-fast neuronal learning models with noise.
AB  - This paper deals with the application of temporal averaging methods to recurrent
      networks of noisy neurons undergoing a slow and unsupervised modification of
      their connectivity matrix called learning. Three time-scales arise for these
      models: (i) the fast neuronal dynamics, (ii) the intermediate external input to
      the system, and (iii) the slow learning mechanisms. Based on this time-scale
      separation, we apply an extension of the mathematical theory of stochastic
      averaging with periodic forcing in order to derive a reduced deterministic model
      for the connectivity dynamics. We focus on a class of models where the activity
      is linear to understand the specificity of several learning rules (Hebbian, trace
      or anti-symmetric learning). In a weakly connected regime, we study the
      equilibrium connectivity which gathers the entire 'knowledge' of the network
      about the inputs. We develop an asymptotic method to approximate this
      equilibrium. We show that the symmetric part of the connectivity post-learning
      encodes the correlation structure of the inputs, whereas the anti-symmetric part
      corresponds to the cross correlation between the inputs and their time
      derivative. Moreover, the time-scales ratio appears as an important parameter
      revealing temporal correlations.

PMID- 23174308
TI  - Biophysical mechanisms regulating AMPA receptor accumulation at synapses.
AB  - Controlling the number of AMPA receptors at synapses is fundamental for fast
      synaptic transmission as well as for long term adaptations in synaptic strength.
      In this review, we examine the biophysical mechanisms implicated in regulating
      AMPAR levels at the cell surface and at synapses. We first describe the structure
      and function of AMPARs, as well as their interactions with various proteins
      regulating their traffic and function. Second we review the vesicular trafficking
      mechanism involving exocytosis and endocytosis, by which AMPARs reach the cell
      surface and are internalized, respectively. Third, we examine the properties of
      lateral diffusion of AMPARs and their trapping at post-synaptic densities.
      Finally, we discuss how these two parallel mechanisms are integrated in time and
      space to control changes in synaptic AMPAR levels in response to plasticity
      protocols. This review highlights the important role of the extra-synaptic AMPAR
      pool, which makes an obligatory link between vesicular trafficking and trapping
      or release at synapses.

PMID- 23174309
TI  - Modulation of allopregnanolone on excitatory transmitters release from single
      glutamatergic terminal.
AB  - Neurosteroids such as allopregnanolone (Allo) are widely distributed in the brain
      and may modulate neuronal excitability under physiological or pathological
      states. Allo modulates GABAA receptor responses, and in this study we
      investigated the functional effects of Allo on presynaptic GABAA receptors on
      single glutamatergic nerve terminal projecting on CA3 neurons. In the present
      study, we measured spontaneous and evoked excitatory postsynaptic currents
      (sEPSCs and eEPSCs), the latter was elicited with single or paired-pulse focal
      electrical stimulation, using mechanically isolated 'synaptic bouton'
      preparation. Allo (10 nM) increased significantly eEPSC amplitude while
      decreasing the failure rate (Rf) and the paired-pulse response ratio (PPR).
      Conversely high concentration (100 nM) of Allo decreased eEPSC amplitude and
      increased Rf and PPR. Allo also increased significantly the frequency and
      amplitude of sEPSCs at low concentrations (10-30 nM) but at high concentration
      (100 nM) it had no effect on current amplitude but modestly decreased sEPSC
      frequency. Application of Allo at nanomolar concentrations facilitated exogenous
      muscimol-induced outward postsynaptic currents but had no effect on glutamate
      induced inward postsynaptic currents. Our results demonstrate that Allo modulates
      glutamate release via presynaptic GABAA receptors, in addition to its better
      characterized effects to modulate postsynaptic GABAA responses. Both pre- and
      postsynaptic GABAA receptor modulation is likely to contribute to the
      physiological actions of neurosteroids.

PMID- 23174310
TI  - Newly identified variability in Brucella canis fatty-acid content is associated
      with geographical origin.
AB  - This study compared the fatty-acid profiles of Brucella canis blood culture
      isolates obtained from infected dogs in the UK, Germany, Japan, South Africa,
      Peru, Mexico, Colombia, and Argentina, and from a human clinical case in
      Argentina, to a bank of isolates obtained from canine outbreaks in the USA.
      Analysis of a total of 42 B. canis isolates and one reference strain found a
      marked variation within the species. Fatty-acid analysis showed that only the
      isolates from Argentina, Colombia, and Mexico, which included the human B. canis
      isolate, contained a specific fatty acid, 19:0 cyclopropane (lactobacillic acid),
      w8c (cis-11,12-methylene octadecanoic acid), and that this fatty acid, when
      present, made up a large percentage of overall fatty-acid content. Prior to this
      study, the cellular fatty-acid 19:0 cyclopropane had been identified in all of
      the species of Brucella considered to be pathogenic to humans (B. abortus, B.
      melitensis, B. suis) except for B. canis. Discovering that this fatty acid not
      only occurs in B. canis, but also that it is only present in some strains of the
      species provides a new focus for investigations aimed at identifying the cause of
      reported geographical variability in human B. canis infection, and at finding
      predictors of biological behaviour and human pathogenicity within this Brucella
      species.

PMID- 23174311
TI  - [Comparative study of schistosomiasis transmission (urinary and intestinal forms)
      at 10 sites in Burkina Faso (in sub-Saharan Africa)].
AB  - Despite great progress in schistosomiasis control over the past decade in Burkina
      Faso, this disease remains a public health problem. This study analyzes
      parasitologic data from investigations of Schistosoma haematobium, S. mansoni,
      and mollusks. The prevalence rate of S. haematobium varies from 3.3% to 50.4%;
      that for S. mansoni (tested only in the western part of the country) from 3.3% to
      39.1%. Prevalence rates are higher in school-aged boys than girls, but the
      reverse is true among adults. Studies of mussels showed the presence of
      Biomphalaria pfeifferi, Bulinus truncatus, Bulinus senegalensis and Bulinus
      globosus in these areas. Our results indicate that behavioral factors as well as
      the dynamics and the distribution of the intermediate mollusks play a major role
      in the persistence of the disease.

PMID- 23174312
TI  - 2H-13C HETCOR MAS NMR for indirect detection of 2H quadrupole patterns and spin
      lattice relaxation rates.
AB  - Two-dimensional (2D) cross-polarization magic angle spinning (CP-MAS) (2)H-(13)C
      heteronuclear correlation (HETCOR) experiments were utilized to indirectly detect
      site-specific deuterium MAS powder patterns. The (2)H-(13)C cross-polarization
      efficiency is orientation-dependent and non-uniform for all crystallites. This
      leads to difficulty in extracting the correct (2)H MAS quadrupole powder
      patterns. In order to obtain accurate deuterium line shapes, (13)C spin lock rf
      field, spin lock rf ramp and CP contact time were carefully calibrated with the
      assistance of theoretical simulations. The extracted quadrupole patterns for U
      [(2)H/(13)C/(15)N]-alanine indicate that the methyl deuterium undergoes classic,
      three-site jumping in the fast motion regime (10(-8)-10(-12)s) and the methine
      deuterium has a rigid deuterium powder pattern. For U-[(2)H/(13)C/(15)N]
      phenylalanine, indirectly detected deuterium line shapes illustrate that the
      aromatic ring undergoes 180 degrees  flips in the fast motion regime while
      (2)Hbeta and (2)Halpha are completely rigid. The experimental deuterium line
      shapes for U-[(2)H/(13)C/(15)N]-proline reflect that (2)Hbeta, (2)Hgamma and
      (2)Hdelta are subjected to fast, two-site reorientations at an angle of (15+/-5)
      degrees , (30+/-5) degrees  and (25+/-10) degrees  respectively. In addition, an
      approach that combines a composite inversion pulse with (2)H-(13)C CP-MAS is
      applied to measure (2)H spin-lattice relaxation times in a site-specific, (13)C
      detected fashion.

PMID- 23174314
TI  - Blockers of adenosine A1, but not muscarinic acetylcholine, receptors improve
      excessive extracellular glutamate-induced synaptic depression.
AB  - We investigated adenosinergic and cholinergic effects on excessive glutamate
      induced depressions of central excitatory synaptic transmissions in vitro. From
      the CA1 region in rat hippocampal slices, orthodromically elicited population
      spikes (PSs) and field excitatory postsynaptic potentials (fEPSPs) at 0.1Hz were
      simultaneously recorded. ANOVA was used for statistics, and p<0.05 was accepted
      as significant. Glutamate (10mM for 10min) completely depressed PSs and fEPSPs,
      which were partially recovered by the following washout for 40min (67.5+/-15.7%
      and 65.4+/-13.9% of the control, respectively, p<0.01, n=12). The recoveries in
      PSs and fEPSPs were exacerbated by edrophonium and carbamoylcholine but improved
      by non- and A1-selective adenosine receptor antagonists (p<0.01, n=6). The
      recovery in PSs, not that in fEPSPs, was exacerbated by adenosine, adenosine A1
      receptor agonist and A2a-receptor antagonist (p<0.01, n=6). The effects of
      edrophonium were blocked by non-, M2- and M4-selective muscarinic acetylcholine
      receptor antagonists (p<0.01, n=6). Excessive glutamate depresses glutamatergic
      excitatory synaptic transmissions, which are exacerbated by muscarinic
      acetylcholine receptor stimulation but improved by adenosine A1 receptor block.
      Somatic excitability is impaired by excessive glutamate with adenosine A1
      receptor stimulation.

PMID- 23174313
TI  - The NO donor sodium nitroprusside: evaluation of skeletal muscle vascular and
      metabolic dysfunction.
AB  - The nitric oxide (NO) donor sodium nitroprusside (SNP) may promote cyanide
      induced toxicity and systemic and/or local responses approaching maximal
      vasodilation. The hypotheses were tested that SNP superfusion of the rat
      spinotrapezius muscle exerts 1) residual impairments in resting and contracting
      blood flow, oxygen utilization (VO(2)) and microvascular O(2) pressure (PO(2)mv);
      and 2) marked hypotension and elevation in resting PO(2)mv. Two superfusion
      protocols were performed: 1) Krebs-Henseleit (control 1), SNP (300 MUM; a dose
      used commonly in superfusion studies) and Krebs-Henseleit (control 2), in this
      order; 2) 300 and 1200 MUM SNP in random order. Spinotrapezius muscle blood flow
      (radiolabeled microspheres), VO(2) (Fick calculation) and PO(2)mv
      (phosphorescence quenching) were determined at rest and during electrically
      induced (1 Hz) contractions. There were no differences in spinotrapezius blood
      flow, VO(2) or PO(2)mv at rest and during contractions pre- and post-SNP
      condition (control 1 and control 2; p>0.05 for all). With regard to dosing, SNP
      produced a graded elevation in resting PO(2)mv (p<0.05) with a reduction in mean
      arterial pressure only at the higher concentration (p<0.05). Contrary to our
      hypotheses, skeletal muscle superfusion with the NO donor SNP (300 MUM) improved
      microvascular oxygenation during the transition from rest to contractions
      (PO(2)mv kinetics) without precipitating residual impairment of muscle
      hemodynamic or metabolic control or compromising systemic hemodynamics. These
      data suggest that SNP superfusion (300 MUM) constitutes a valid and important
      tool for assessing the functional roles of NO in resting and contracting skeletal
      muscle function without incurring residual alterations consistent with cyanide
      accumulation and poisoning.

PMID- 23174315
TI  - How does the inclusion of twins conceived via fertility treatments influence the
      results of twin studies?
AB  - Rates of twinning have risen dramatically over the last 30 years, from 1 in 53
      births in 1980 to 1 in 30 births in 2009 (Martin et al. (January 2012). Three
      decades of twin births in the United States, 1980-2009. Atlanta, GA: Centers for
      Disease Control and Prevention, National Center for Health Statistics). This
      increase is largely attributable to increases in the use of fertility treatments
      (i.e., ovulation induction and in vitro fertilization) combined with delays in
      parenthood. Although this increase means that more twins are available for
      recruitment into twin studies, it also has potential consequences for the
      heritability estimates obtained in these studies. This study sought to evaluate
      this possibility, making use of the ongoing Michigan Twins Project (N = 7,261
      families with twins aged 3-17 years), an arm of the Michigan State University
      Twin Registry. Results revealed that, on average, twins conceived via fertility
      treatments had lower rates of behavior problems than those conceived naturally,
      although these behavioral differences could be explained largely by demographic
      and socio-economic differences across the two types of twin families. Twin
      similarity did not meaningfully differ across fertility treatment status. We thus
      conclude that estimates of genetic and environmental influences obtained from
      twin studies over the last 10-15 years are more or less unaffected by the
      inclusion of twins conceived via fertility treatments in their samples.

PMID- 23174316
TI  - Halogenated flavanones as potential apoptosis-inducing agents: synthesis and
      biological activity evaluation.
AB  - A series of halogenated flavanones were synthesized from 2-hydroxychalcones and
      tested for their cytotoxicity against a panel of human cancer cell lines. Among
      the synthesized compounds, 3',7-dichloroflavanone (2d) showed the highest
      activity against MCF-7, LNCaP, PC3, Hep-G2, KB and SK-N-MC cells. However, 3',6
      dichloroflavanone (2g) with IC(50) value of 2.9 +/- 0.9 MUM was the most potent
      compound against MDA-MB-231 cells, being approximately 12 times more active than
      etoposide as reference drug. According to the flow-cytometric analysis, compound
      2g can induce apoptosis by 66.19 and 21.37% in PC3 and MDA-MB-231 cells,
      respectively. The results of acridine orange/ethidium bromide staining and TUNEL
      assay suggested that the cytotoxic activity of this compound in PC3 and MDA-MB
      231 cells occurs via apoptosis.

PMID- 23174317
TI  - Synthesis of N,N'-bis(5-arylidene-4-oxo-3,5-dihydro-4H-imidazol-2-yl)diamines
      bearing various linkers and biological evaluation as potential inhibitors of
      kinases.
AB  - The synthesis in 4 steps of new N,N'-bis(5-arylidene-4-oxo-3,5-dihydro-4H
      imidazol-2-yl)diamines issued from various symmetric primary diamines as linkers
      was reported. The key step of our strategy has been the sulphur/nitrogen
      displacement of (5Z)-5-arylidene-2-ethylsulfanyl-3,5-dihydro-4H-imidazol-4-ones 6
      with respectively ethylenediamine 7a, piperazine 7b and N,N'-bis(3
      aminopropyl)piperazine 7c using solvent-free reaction conditions under microwave
      irradiation with retention of configuration. These compounds were tested for
      their kinase inhibitory potencies toward four kinases (GSK-3alpha/beta, DYRK1A,
      CLK1 and CLK3).

PMID- 23174318
TI  - Isoprenyl-thiourea and urea derivatives as new farnesyl diphosphate analogues:
      synthesis and in vitro antimicrobial and cytotoxic activities.
AB  - A series of new isoprenyl-thiourea and urea derivatives were synthesized by the
      reaction of alkyl or aryl isothiocyanate or isocyanate and primary amines. The
      structures of the compounds were established by (1)H NMR, (13)C NMR, MS, HRMS and
      elemental analysis. The new compounds were screened for in vitro antimicrobial
      activity against seven strains representing different types of gram-positive and
      gram-negative bacteria. More than a third of the synthesized compounds showed
      variable inhibition activities against the tested strains. Best antimicrobial
      activities were found for those thiourea analogues with 3-methyl-2-butenyl,
      isobutyl or isopentyl groups and aromatic rings possessing electron withdrawing
      substituents. The new compounds were also subjected to a preliminary screening
      for antitumoral activity. The presence of a highly lipophilic group and an
      electron withdrawing group in the aromatic rings enhanced anticancer activity of
      the synthesized compounds, showing in most cases more activity than that of the
      controls.

PMID- 23174319
TI  - Blunt abdominal aortic trauma in paediatric patients.
AB  - BACKGROUND: Blunt abdominal aortic trauma (BAAT) is a very rare occurrence in
      children, with significant morbidity and mortality. Varied clinical presentations
      and sparse literature evidence make it difficult to define the proper management
      policy for paediatric patients. METHOD: We report our centre's data on three
      consecutive children with BAAT managed between 2006 and 2010. A Medline search
      was also performed for relevant publications since 1966, together with a review
      of references in retrieved publications. RESULTS: Forty children (range 1-16
      years) were included in our final analysis. Motor vehicle crashes (MVC) were the
      leading cause of injury (65%). The in-hospital mortality rate was 7.5% (3/40).
      Nine patients (22.5%) ended up with residual sequelae. Main primary aortic
      lesions were complete wall rupture (12.5%), intimal transection (70%) and
      pseudoaneurysm (15%). Twenty-eight children underwent aortic surgical repair
      (70%). Among the 12 non-operatively managed patients, 41.6% had complications,
      including one death. CONCLUSION: Symptomatic lesions and complete ruptures should
      undergo immediate surgical repair. Circumferential intimal transections are at
      high risk of complication and should also receive intervention. Partial intimal
      transections and delayed pseudoaneurysms can be initially observed by clinical
      examination and imaging. Patients with these latter pathologies should be
      operated on at any sign of deterioration.

PMID- 23174320
TI  - Neuroendocrine responses of a crustacean host to viral infection: effects of
      infection of white spot syndrome virus on the expression and release of
      crustacean hyperglycemic hormone in the crayfish Procambarus clarkii.
AB  - The objectives of the present study were to characterize the changes in
      crustacean hyperglycemic hormone (CHH) transcript and peptide levels in response
      to infection of white spot syndrome virus (WSSV) in a crustacean, Procambarus
      clarkii. After viral challenge, significant increase in virus load began at 24 h
      post injection (hpi) and the increase was much more substantial at 48 and 72 hpi.
      The hemolymph CHH levels rapidly increased after viral challenge; the increase
      started as early as 3 hpi and lasted for at least 2 d after the challenge. In
      contrast, the hemolymph glucose levels did not significantly changed over a 2 d
      period in the WSSV-infected animals. The CHH transcript and peptide levels in
      tissues were also determined. The CHH transcript levels in the eyestalk ganglia
      (the major site of CHH synthesis) of the virus-infected animals did not
      significantly change over a 2 d period and those in 2 extra-eyestalk tissues (the
      thoracic ganglia and cerebral ganglia) significantly increased at 24 and 48 hpi.
      The CHH peptide levels in the eyestalk ganglia of the virus-infected animals
      significantly decreased at 24 and 48 hpi and those in the thoracic ganglia and
      cerebral ganglia remained unchanged over a 2 d period. These data demonstrated a
      WSSV-induced increase in the release of CHH into hemolymph that is rapid in onset
      and lasting in duration. Changes in the CHH transcript and peptide levels implied
      that the WSSV-induced increase in hemolymph CHH levels primarily resulted from an
      enhanced release from the eyestalk ganglia, but the contribution of the 2 extra
      eyestalk tissues to hemolymph pool of CHH increased as viral infection
      progressed. The combined patterns of change in the hemolymph glucose and CHH
      levels further suggest that the virus-enhanced CHH release would lead to higher
      glycolytic activity and elevated glucose mobilization presumably favorable for
      viral replication.

PMID- 23174321
TI  - Scapulothoracic dissociation.
AB  - Scapulothoracic dissociation is rare, resulting from high-energy trauma to the
      shoulder girdle and disruption of the scapulothoracic articulation. The
      associated musculoskeletal, vascular, and neurologic injuries carry potentially
      devastating outcomes. Overall outcomes seem to be closely related to the degree
      of neurologic impairment sustained. However, given the wide spectrum of injury in
      scapulothoracic dissociation and limited data concerning outcomes, general
      recommendations regarding the management of this injury have been difficult to
      discern. This article reviews the current data regarding the evaluation,
      diagnosis, treatment, and outcomes after scapulothoracic dissociation.

PMID- 23174322
TI  - Fractures of the proximal humerus.
AB  - Proximal humeral fractures are common, with low-energy injuries occurring in the
      elderly population and less frequent high-energy fractures striking young people.
      This article discusses the anatomy, clinical evaluation, and treatment of these
      fractures.

PMID- 23174323
TI  - Emerging concepts in upper extremity trauma: humeral shaft fractures.
AB  - Fractures of the humeral shaft are common in low-energy and high-energy trauma,
      and optimal clinical management remains controversial. Nonsurgical management has
      been supported as the preferred treatment based on high union rates and minimal
      functional deficit due to a rich vascular supply from overlying muscle and the
      wide motion available at the glenohumeral joint. Recent studies of nonoperative
      management have challenged surgeons' understanding of these fractures and the
      perception of favorable outcomes. Current considerations support expanded
      operative indications with traditional open-plate fixation and with the use of
      minimally invasive techniques, implants, and a reconsideration of intramedullary
      nailing.

PMID- 23174324
TI  - Intra-articular distal humerus fractures.
AB  - Distal humeral fractures are relatively rare and complex injuries. With
      appropriate preoperative planning and execution of surgical technique, good
      outcomes may be obtained in most patients. Patients should be counseled regarding
      loss of motion in these injuries, and elderly, osteoporotic patients with
      extensive comminution should be considered for total elbow arthroplasty as an
      alternative to open reduction and internal fixation.

PMID- 23174325
TI  - Terrible triad of the elbow.
AB  - The terrible triad of the elbow is a difficult injury with historically poor
      outcomes. Improved experience, techniques, and implants have advanced to the
      point where restoration of elbow stability can be expected. Careful attention to
      each destabilizing element of the injury pattern is essential and places high
      demands on the surgeon's mastery of the anatomic complexity of the elbow.
      Technically, the surgeon must bring every skill to bear, as soft tissue
      techniques, fracture repair, and joint arthroplasty are routinely required to
      adequately treat these complex constellations of injury.

PMID- 23174326
TI  - Monteggia fractures.
AB  - Monteggia described a fracture of the proximal third of the ulna with anterior
      dislocation of the radial head from both the proximal radioulnar and
      radiocapitellar joints. Application of this eponym to all injuries with
      radiocapitellar subluxation or dislocation has led to some confusion. In
      addition, there are substantial differences between Monteggia injuries in
      children and adults. With careful definition, specific subsets of patients may
      benefit from consideration as a separate type of Monteggia injury.

PMID- 23174327
TI  - Proximal forearm fractures.
AB  - Unfortunately, the literature has little guidance for revision elbow surgery.
      This article attempts to supplement what is known in the literature with the
      author's anecdotal experience. With this article, it is the author's hope that
      the reader may learn from his or her successes and his or her failures without
      having to discover them first hand. There is good reason for angst to overcome
      surgeons looking at radiographs depicting a traumatized proximal ulna or radius.
      Surgeons know that there is a good chance they will be seeing these patients for
      a long time.

PMID- 23174328
TI  - Complex distal radius fractures.
AB  - Complex distal radius fractures are high-energy injuries of the wrist with
      articular disruption, ligamentous instability, significant comminution, soft
      tissue injury, and/or neurovascular impairment. The management of these injuries
      requires a thorough understanding of wrist functional anatomy and familiarity
      with a wide selection of approach and fixation options. This article reviews an
      approach that involves structured evaluation, aggressive soft tissue management,
      early reduction and skeletal stabilization, and a columnar approach to definitive
      care. Outcome is determined by multiple factors and depends greatly on the soft
      tissue injury, patient factors, and management and the adequacy of restoration of
      osseous and ligamentous relationships.

PMID- 23174329
TI  - Fracture-dislocations of the carpus: perilunate injury.
AB  - The progressive perilunar instability model described by Mayfield is still used
      to predict the pattern of injury. Diagnosis of injury and clinical and
      radiographic findings depend on the pattern of injury. Open procedures are
      preferred for anatomic reduction after initial closed reduction is performed for
      acute injuries. A dorsal, volar, or combined dorsal/volar approach may be
      necessary and is often decided by surgeon preference. Loss of motion and
      diminished grip strength are common consequences despite appropriate treatment.
      Successful outcomes depend on time to treatment, open or closed nature of injury,
      extent of chondral damage, residual instability, and fracture union.

PMID- 23174330
TI  - The scaphoid.
AB  - The scaphoid is vitally important for the proper mechanics of wrist function. Its
      unique morphology from its boat like shape to its retrograde blood supply can
      present with challenges in the presence of a fracture. Almost completely covered
      with articular cartilage, this creates precise surface loading demands and
      intolerance to bony remodeling. Fracture location compounds risk of malunion and
      non-union. Scaphoid fractures may significantly impair wrist function and
      activities of daily living, with both individual and economic consequences.

PMID- 23174331
TI  - From the scapula to the scaphoid.

PMID- 23174332
TI  - Interconversion of CO2 and formic acid by bio-inspired Ir complexes with pendent
      bases.
AB  - Recent investigations of the interconversion of CO2 and formic acid using Ru, Ir
      and Fe complexes are summarized in this review. During the past several years,
      both the reaction rates and catalyst stabilities have been significantly
      improved. Remarkably, the interconversion (i.e., reversibility) has also been
      achieved under mild conditions in environmentally benign water solvent by
      slightly changing the pH of the aqueous solution. Only a few catalysts seem to
      reflect a bio-inspired design such as the use of proton responsive ligands,
      ligands with pendent bases or acids for a second-coordination-sphere interaction,
      electroresponsive ligands, and/or ligands having a hydrogen bonding function with
      a solvent molecule or an added reagent. The most successful of these is an
      iridium dinuclear complex catalyst that at least has the first three of these
      characteristics associated with its bridging ligand. By utilizing an acid/base
      equilibrium for proton removal, the ligand becomes a strong electron donor,
      resulting in Ir(I) character with a vacant coordination site at each metal center
      in slightly basic solution. Complemented by DFT calculations, kinetic studies of
      the rates of formate production using a related family of Ir complexes with and
      without such functions on the ligand reveal that the rate-determining step for
      the CO2 hydrogenation is likely to be H2 addition through heterolytic cleavage
      involving a "proton relay" through the pendent base. The dehydrogenation of
      formic acid, owing to the proton responsive ligands changing character under
      slightly acidic pH conditions, is likely to occur by a mechanism with a different
      rate-determining step. This article is part of a Special Issue entitled: Metals
      in Bioenergetics and Biomimetics Systems. 

PMID- 23174333
TI  - The role of complex II in disease.
AB  - Genetically defined mitochondrial deficiencies that result in the loss of complex
      II function lead to a range of clinical conditions. An array of tumor syndromes
      caused by complex II-associated gene mutations, in both succinate dehydrogenase
      and associated accessory factor genes (SDHA, SDHB, SDHC, SDHD, SDHAF1, SDHAF2),
      have been identified over the last 12 years and include hereditary paraganglioma
      pheochromocytomas, a diverse group of renal cell carcinomas, and a specific
      subtype of gastrointestinal stromal tumors (GIST). In addition, congenital
      complex II deficiencies due to inherited homozygous mutations of the catalytic
      components of complex II (SDHA and SDHB) and the SDHAF1 assembly factor lead to
      childhood disease including Leigh syndrome, cardiomyopathy and infantile
      leukodystrophies. The role of complex II subunit gene mutations in tumorigenesis
      has been the subject of intensive research and these data have led to a variety
      of compelling hypotheses. Among the most widely researched are the stabilization
      of hypoxia inducible factor 1 under normoxia, and the generation of reactive
      oxygen species due to defective succinate:ubiquinone oxidoreductase function.
      Further progress in understanding the role of complex II in disease, and in the
      development of new therapeutic approaches, is now being hampered by the lack of
      relevant cell and animal models. This article is part of a Special Issue
      entitled: Respiratory complex II: Role in cellular physiology and disease.

PMID- 23174334
TI  - Silent Spring after 50 years.
AB  - As Silent Spring passed the half-century mark, historians have continued to
      reflect on its significance. For this issue of Endeavour, we drew together six
      articles that explore a few of the many legacies of this remarkable book. Given
      the impressive scope and breadth of the papers in this issue, it is clear that
      Silent Spring, and the shock waves surrounding its publication, continue to
      provide rich fodder for historical analysis.

PMID- 23174335
TI  - Functional relationships for investigating cognitive processes.
AB  - Functional relationships (from systematic manipulation of critical variables) are
      advocated for revealing fundamental processes of (comparative) cognition-through
      examples from my work in psychophysics, learning, and memory. Functional
      relationships for pigeon wavelength (hue) discrimination revealed best
      discrimination at the spectral points of hue transition for pigeons-a
      correspondence (i.e., functional relationship) similar to that for humans.
      Functional relationships for learning revealed: Item-specific or relational
      learning in matching to sample as a function of the pigeons' sample-response
      requirement, and same/different abstract-concept learning as a function of the
      training set size for rhesus monkeys, capuchin monkeys, and pigeons. Functional
      relationships for visual memory revealed serial position functions (a 1st order
      functional relationship) that changed systematically with retention delay (a 2nd
      order relationship) for pigeons, capuchin monkeys, rhesus monkeys, and humans.
      Functional relationships for rhesus-monkey auditory memory also revealed
      systematic changes in serial position functions with delay, but these changes
      were opposite to those for visual memory. Functional relationships for proactive
      interference revealed interference that varied as a function of a ratio of delay
      times. Functional relationships for change detection memory revealed
      (qualitative) similarities and (quantitative) differences in human and monkey
      visual short-term memory as a function of the number of memory items. It is
      concluded that these findings were made possible by varying critical variables
      over a substantial portion of the manipulable range to generate functions and
      derive relationships.

PMID- 23174336
TI  - Repeated visual distracter exposure enhances new discrimination learning and
      sustained attention task performance in rats.
AB  - Repeated exposure to distraction requires attentional effort to restore task
      performance. However, the impact of repeated distracter exposure and exertion of
      attentional effort on new learning has not been examined. In the present
      experiment, rats were trained in a two-lever sustained attention task. Rats then
      continued to train, for 12 sessions, in this task either with or without a
      flashing houselight distracter throughout the session. The flashing houselight
      transiently decreased attentional performance. Trials that were part of a new
      light-location discrimination task were then interspersed within the sustained
      attention task sessions. The frequency of these new light-location discrimination
      trials increased with additional training. Rats exposed to the distracter
      exhibited higher accuracy levels during some blocks of sessions in the new light
      location discrimination task trials and in the remaining sustained attention task
      trials compared to rats that were not exposed to the distracter. The effects of
      repeated distracter exposure are interpreted in the context of an "occasion
      setting" model that has been used to describe performance in this task.

PMID- 23174337
TI  - Categorization of birds, mammals, and chimeras by pigeons.
AB  - Identifying critical features that control categorization of complex polymorphous
      pictures by animals remains a challenging and important problem. Toward this
      goal, experiments were conducted to isolate the properties controlling the
      categorization of two pictorial categories by pigeons. Pigeons were trained in a
      go/no-go task to categorize black and white line drawings of birds and mammals.
      They were then tested with a variety of familiar and novel exemplars of these
      categories to examine the features controlling this categorization. These tests
      suggested the pigeons were segregating and using the principal axis of
      orientation of the animal figures as the primary means of discriminating each
      category, although other categorical and item-specific cues were likely involved.
      This perceptual/cognitive reduction of the categorical stimulus space to a few
      visual features or dimensions is likely a characteristic of this species'
      processing of complex pictorial discrimination problems and is a critical
      property for theoretical accounts of this behavior.

PMID- 23174338
TI  - Hydroxyapatite bioactivated bacterial cellulose promotes osteoblast growth and
      the formation of bone nodules.
AB  - The goal of this study was to investigate the feasibility of bacterial cellulose
      (BC) scaffold to support osteoblast growth and bone formation. BC was produced by
      culturing Acetobacter xylinum supplemented with hydroxyapatite (HA) to form BC
      membranes (without HA) and BC/HA membranes. Membranes were subjected to X-ray
      photoelectron spectroscopy (XPS) analysis to determine surface element
      composition. The membranes were further used to evaluate osteoblast growth,
      alkaline phosphatase activity and bone nodule formation. BC was free of calcium
      and phosphate. However, XPS analysis revealed the presence of both calcium (10%)
      and phosphate (10%) at the surface of the BC/HA membrane. Osteoblast culture
      showed that BC alone was non-toxic and could sustain osteoblast adhesion.
      Furthermore, osteoblast adhesion and growth were significantly (p <=0.05)
      increased on BC/HA membranes as compared to BC alone. Both BC and BC/HA membranes
      improved osteoconductivity, as confirmed by the level of alkaline phosphatase
      (ALP) activity that increased from 2.5 mM with BC alone to 5.3 mM with BC/HA.
      BC/HA membranes also showed greater nodule formation and mineralization than the
      BC membrane alone. This was confirmed by Alizarin red staining (ARS) and energy
      dispersive X-ray spectroscopy (EDX). This work demonstrates that both BC and
      BC/HA may be useful in bone tissue engineering.

PMID- 23174339
TI  - Occurrence of pathogens in wild rodents caught on Swedish pig and chicken farms.
AB  - A total of 207 wild rodents were caught on nine pig farms, five chicken farms and
      five non-farm locations in Sweden and surveyed for a selection of bacteria,
      parasites and viruses. Lawsonia intracellularia and pathogenic Yersinia
      enterocolitica were only detected in rodents on pig farms (9% and 8% prevalence,
      respectively) which indicate that these agents are more likely to be transmitted
      to rodents from pigs or the environment on infected farms. Brachyspira
      hyodysenteriae (1%), Brachyspira intermedia (2%), Campylobacter jejuni (4%),
      Campylobacter upsaliensis (2%), leptospires (7%) and encephalomyocarditis virus
      (9%) were also detected from rodents not in contact with farm animals. Giardia
      and Cryptosporidium spp. were common, although no zoonotic types were verified,
      and Salmonella enterica was isolated from 1/11 mice on one farm but not detected
      by PCR from any of the rodents. Trichinella spp. and Toxoplasma gondii were not
      detected.

PMID- 23174340
TI  - Pharmacological and behavioral characterization of the novel CRF1 antagonist BMS
      763534.
AB  - BMS-763534 is a potent (CRF(1) IC(50) = 0.4 nM) and selective (>1000-fold
      selectivity vs. all other sites tested) CRF(1) receptor antagonist (pA2 = 9.47
      vs. CRF(1)-mediated cAMP production in Y79 cells). BMS-763534 accelerated the
      dissociation of (125)I-o-CRF from rat frontal cortex membrane CRF(1) receptors
      consistent with a negative allosteric modulation of CRF binding. BMS-763534
      produced dose-dependent increases in CRF(1) receptor occupancy and anxiolytic
      efficacy; lowest effective anxiolytic dose = 0.56 mg/kg, PO, which was associated
      with 71 +/- 5% CRF(1) receptor occupancy of frontoparietal CRF(1) receptors.
      Sedative/ataxic effects of BMS-763534 were only observed at high dose multiples
      (54-179*) relative to the lowest dose required for anxiolytic efficacy. At doses
      of 5- to 18-fold higher than the lowest efficacious dose in the anxiety assay,
      BMS-763534 shared subjective effects with the benzodiazepine chlordiazepoxide.
      Interestingly BMS-790318, the O-demethylated metabolite of BMS-763534, showed
      weak affinity for the TBOB site of the GABA(A) receptor (67% inhibition at 10
      MUM) and augmented GABA evoked currents (EC(50) = 1.6 MUM). Thus, the
      unanticipated signal in the drug discrimination assay may have resulted from an
      interaction of the metabolite BMS-790318 with the TBOB site on the GABA(A)
      channel where it appears to behave as an allosteric potentiator of GABA evoked
      currents.

PMID- 23174341
TI  - Potentiation of mGlu7 receptor-mediated glutamate release at nerve terminals
      containing N and P/Q type Ca2+ channels.
AB  - Calcium channels that mediate glutamate release (N-type and P/Q-type) are
      expressed in distinct populations of cerebrocortical nerve terminals in adult
      mice. mGlu7 receptors are exclusively expressed in nerve terminals containing N
      type Ca(2+) channels, which are less tightly coupled to glutamate release than
      P/Q-type Ca(2+) channels. We recently reported that in addition to inhibit, mGlu7
      receptors can also potentiate glutamate release via phosphatidyl inositol (4,5)
      bisphosphate hydrolysis and activation of the non-kinase diacylglycerol binding
      protein Munc13-1, a protein that primes synaptic vesicles for exocytosis. Here,
      we assessed whether mGlu7 receptor-mediated potentiation of glutamate release is
      restricted to nerve terminals expressing N-type Ca(2+) channels to compensate for
      their weak coupling to release. In the hippocampus, mGlu7 receptors are expressed
      both in nerve terminals containing N-type Ca(2+) channels and in nerve terminals
      containing P/Q-type Ca(2+) channels. When analyzed, we observed potentiation of
      mGlu7 receptor mediated release in wild type hippocampal nerve terminals at
      physiological (1.3 mM) and low (0.1 mM) concentrations of external Ca(2+). By
      contrast, in nerve terminals from mice lacking the alpha1B subunit of N-type
      channels (Ca(v)2.2), in which evoked release is mediated by P/Q-type channels
      only, no release potentiation was observed at 1.3 mM Ca(2+). We conclude that
      release potentiation at 1.3 mM [Ca(2+)](e) occurs in nerve terminals expressing N
      type channels, whereas that which occurs at low 0.1 mM [Ca(2+)](e) represents the
      release from nerve terminals containing P/Q-type Ca(2+) channels. Although, mGlu7
      receptor mediated potentiation is independent of Ca(2+) channel activity, as it
      was induced by the Ca(2+) ionophore ionomycin, release potentiation is influenced
      by the Ca(2+) channel type and/or the associated release machinery.

PMID- 23174343
TI  - [Neuropathic pain during tuberculosis treatment in Bamako (Mali)].
AB  - BACKGROUND: The incidence of tuberculosis is high in Africa. It is treated with
      medications that can trigger neuropathic pain and thus negatively affect
      patients' quality of life and treatment compliance. The aim of this study was to
      investigate neuropathic pain due to antituberculosis drugs in patients without
      HIV infection. METHODS: This prospective study, conducted in the pulmonology
      department of the University Hospital of Point G, Mali, included patients taking
      antituberculosis drugs who had negative HIV tests and no other potential cause of
      neuropathic pain. Diagnosis of neuropathic pain relied on the DN4 questionnaire
      (4 questions for neuropathic pain) and its assessment on a visual analog scale
      (VAS) and the Lattinen test. RESULTS: During the study period, 423 subjects were
      admitted to our department, 103 (24.4%) with tuberculosis. Eighty met the
      inclusion criteria. The sex ratio (male to female) was 2.5. Their mean age was 39
      years (range: 13-80). In all, 13 (16.25%) reported neuropathic pain. Burning
      sensations in the plantar region, with or without paresthesia, were the
      presenting symptoms in 10 of them. All patients began a treatment based on
      amitriptyline, vitamin B6, and physical therapy and all reported improvement
      within 2 months. CONCLUSION: Neuropathic pain occurs independently of age, sex or
      the specific antituberculosis regimen, as long as it includes isoniazid. Stopping
      or modifying the treatment regimen is not necessary. In our context, in view of
      the difficulties in identifying slow acetylators, the routine addition of vitamin
      B6 to all treatment protocols should be discussed.

PMID- 23174342
TI  - Inflammatory T helper 17 cells promote depression-like behavior in mice.
AB  - BACKGROUND: Recognition of substantial immune-neural interactions is revising
      dogmas about their insular actions and revealing that immune-neural interactions
      can substantially impact central nervous system functions. The inflammatory
      cytokine interleukin-6 promotes susceptibility to depression and drives
      production of inflammatory T helper 17 (Th17) T cells, raising the hypothesis
      that in mouse models, Th17 cells promote susceptibility to depression-like
      behaviors. METHODS: Behavioral characteristics were measured in male mice
      administered Th17 cells, CD4(+) cells, or vehicle and in retinoid-related orphan
      receptor-gammaT (RORgammaT)(+/GFP) mice or male mice treated with RORgammaT
      inhibitor or anti-interleukin-17A antibodies. RESULTS: Mouse brain Th17 cells
      were elevated by learned helplessness and chronic restraint stress, two common
      depression-like models. Th17 cell administration promoted learned helplessness in
      89% of mice in a paradigm where no vehicle-treated mice developed learned
      helplessness, and impaired novelty suppressed feeding and social interaction
      behaviors. Mice deficient in the RORgammaT transcription factor necessary for
      Th17 cell production exhibited resistance to learned helplessness, identifying
      modulation of RORgammaT as a potential intervention. Treatment with the RORgammaT
      inhibitor SR1001, or anti-interleukin-17A antibodies to abrogate Th17 cell
      function, reduced Th17-dependent learned helplessness. CONCLUSIONS: These
      findings indicate that Th17 cells are increased in the brain during depression
      like states, promote depression-like behaviors in mice, and specifically
      inhibiting the production or function of Th17 cells reduces vulnerability to
      depression-like behavior, suggesting antidepressant effects may be attained by
      targeting Th17 cells.

PMID- 23174344
TI  - G * E interaction and neurodevelopment I. Focus on maltreatment.
AB  - In a short series of articles, we will review the evidence for genotype by
      environment interaction (G * E) in developmental psychopathology. We will focus
      specifically on the characteristics of types of exposure assessed with respect to
      both their methods and findings. This article aims to review the studies
      exploring the effects of child maltreatment on children, adolescents and young
      adults closer in time to maltreatment experience, in a G * E perspective.

PMID- 23174345
TI  - Mapping urban pipeline leaks: methane leaks across Boston.
AB  - Natural gas is the largest source of anthropogenic emissions of methane (CH(4))
      in the United States. To assess pipeline emissions across a major city, we mapped
      CH(4) leaks across all 785 road miles in the city of Boston using a cavity-ring
      down mobile CH(4) analyzer. We identified 3356 CH(4) leaks with concentrations
      exceeding up to 15 times the global background level. Separately, we measured
      delta(13)CH(4) isotopic signatures from a subset of these leaks. The
      delta(13)CH(4) signatures (mean = -42.80/00 +/- 1.30/00 s.e.; n = 32) strongly
      indicate a fossil fuel source rather than a biogenic source for most of the
      leaks; natural gas sampled across the city had average delta(13)CH(4) values of 
      36.80/00 (+/- 0.70/00 s.e., n = 10), whereas CH(4) collected from landfill sites,
      wetlands, and sewer systems had delta(13)CH(4) signatures ~200/00 lighter (MU = 
      57.80/00, +/- 1.60/00 s.e., n = 8). Repairing leaky natural gas distribution
      systems will reduce greenhouse gas emissions, increase consumer health and
      safety, and save money.

PMID- 23174346
TI  - Evaluation of food and beverage television advertising during children's viewing
      time in Spain using the UK nutrient profile model.
AB  - OBJECTIVE: To evaluate the nutritional quality of products advertised on
      television (TV) during children's viewing time in Spain, applying the UK nutrient
      profile model (UKNPM). DESIGN: We recorded 80 h of four general TV station
      broadcasts during children's time in May and June 2008, and identified all
      advertisements for foods and beverages. Nutritional information was obtained from
      the product labels or websites and from food composition tables. Each product was
      classified as healthy (e.g. gazpacho, a vegetable juice) or less healthy (e.g.
      potato crisp snacks) according to the UKNPM criteria. SETTING: Four free-of
      charge TV channels in Spain: two national channels and two regional ones.
      SUBJECTS: TV commercials of food and beverages. RESULTS: A total of 486
      commercials were broadcast for ninety-six different products, with a mean
      frequency of 5?1 advertisements per product. Some 61?5% of the ninety-six
      products were less healthy, and the percentage was higher for foods (74?1 %). All
      (100 %) of the breakfast cereals and 80% of the non-alcoholic drinks and soft
      drinks were less healthy. Of the total sample of commercials, 59?7% were for less
      healthy products, a percentage that rose to 71?2% during children's reinforced
      protection viewing time. CONCLUSIONS: Over half the commercials were for less
      healthy products, a proportion that rose to over two-thirds during the hours of
      special protection for children. This suggests that applying the UKNPM to
      regulate food advertising during this slot would entail the withdrawal of most
      food commercials in Spain. TV advertising of products with low nutritional
      quality should be restricted.

PMID- 23174347
TI  - High concentrations of visfatin in the peripheral blood of patients with acute
      basal ganglia hemorrhage are associated with poor outcome.
AB  - Higher plasma visfatin concentration has been associated with clinical outcomes
      of traumatic brain injury. No published information exists to date about change
      in plasma visfatin after intracerebral hemorrhage. This study included one
      hundred and twenty-eight healthy controls and 128 patients with intracerebral
      hemorrhage. The unfavorable outcome was defined as modified Rankin Scale score >2
      at 6 months. The patients had higher plasma visfatin measurements than control
      subjects. Plasma visfatin levels were highly correlated with National Institutes
      of Health Stroke Scale score and plasma C-reactive protein levels in the
      patients. A multivariate analysis identified plasma visfatin level as an
      independent predictor for 6-month mortality and unfavorable outcome. According to
      receiver operating characteristic curve analysis, the predictive value of the
      plasma visfatin concentration was similar to National Institutes of Health Stroke
      Scale score. In a combined logistic-regression model, visfatin improved the
      predictive value of National Institutes of Health Stroke Scale score for 6-month
      unfavorable outcome. Thus, increased plasma visfatin level is associated with 6
      month clinical outcomes after intracerebral hemorrhage.

PMID- 23174348
TI  - Antifungal peptides homologous to the Penicillium chrysogenum antifungal protein
      (PAF) are widespread among Fusaria.
AB  - Putative antifungal peptide encoding genes containing Penicillium chrysogenum
      antifungal protein (PAF) characteristic amino acid motifs were identified in 15
      Fusarium isolates, representing 10 species. Based on the predicted sequences of
      mature peptides, discrepancy in one, two or three amino acids was observed
      between them. Phylogenetic investigations revealed that they show high amino acid
      sequence similarity to PAF and they belong to the group of fungal derived
      antifungal peptides with PAF-cluster. Ten from the 15 partially purified <10 kDa
      peptide fraction of Fusarium ferment broths showed antifungal activity. The
      presence of approximately 6.3 kDa molecular weight peptides was detected in all
      of the antifungally active ferment broths, and this peptide was isolated and
      purified from Fusarium polyphilaidicum. The minimal inhibitiory concentrations of
      F. polyphilaidicum antifungal protein (FPAP) were determined against different
      filamentous fungi, yeasts and bacteria. Filamentous fungal species were the most
      susceptible to FPAF, but some yeasts were also slightly sensitive.

PMID- 23174349
TI  - New analogs of the CART peptide with anorexigenic potency: the importance of
      individual disulfide bridges.
AB  - The CART (cocaine- and amphetamine-regulated transcript) peptide is an
      anorexigenic neuropeptide that acts in the hypothalamus. The receptor and the
      mechanism of action of this peptide are still unknown. In our previous study, we
      showed that the CART peptide binds specifically to PC12 rat pheochromocytoma
      cells in both the native and differentiated into neuronal phenotype. Two
      biologically active forms, CART(55-102) and CART(61-102), with equal biological
      activity, contain three disulfide bridges. To clarify the importance of each of
      these disulfide bridges in maintaining the biological activity of CART(61-102),
      an Ala scan at particular S-S bridges forming cysteines was performed, and
      analogs with only one or two disulfide bridges were synthesized. In this study, a
      stabilized CART(61-102) analog with norleucine instead of methionine at position
      67 was also prepared and was found to bind to PC12 cells with an anorexigenic
      potency similar to that of CART(61-102). The binding study revealed that out of
      all analogs tested, [Ala(68,86)]CART(61-102), which contains two disulfide
      bridges (positions 74-94 and 88-101), preserved a high affinity to both native
      PC12 cells and those that had been differentiated into neurons. In food intake
      and behavioral tests with mice after intracerebroventricular administration, this
      analog showed strong and long-lasting anorexigenic potency. Therefore, the
      disulfide bridge between cysteines 68 and 86 in CART(61-102) can be omitted
      without a loss of biological activity, but the preservation of two other
      disulfide bridges and the full-length peptide are essential for biological
      activity.

PMID- 23174350
TI  - HIV-1 p6 - a structured to flexible multifunctional membrane-interacting protein.
AB  - The human immunodeficiency virus type 1 (HIV-1) p6 protein has recently been
      recognized as a docking site for several cellular and viral binding partners and
      is important for the formation of infectious viruses. Most of its known functions
      are suggested to occur under hydrophobic conditions near the cytoplasmic
      membrane, where the protein is presumed to exist in its most structured state.
      Although p6 is involved in manifold specific interactions, the protein has
      previously been considered to possess a random structure in aqueous solution. We
      show that p6 exhibits a defined structure with N- and C-terminal helical domains,
      connected by a flexible hinge region in 100mM dodecylphosphocholine micelle
      solution at pH 7 devoid of any organic co-solvents, indicating that this is a
      genuine limiting structural feature of the molecule in a hydrophobic environment.
      Furthermore, we show that p6 directly interacts with a cytoplasmic model membrane
      through both N-terminal and C-terminal regions by use of surface plasmon
      resonance (SPR) spectroscopy. Phosphorylation of Ser-40 located in the center of
      the C-terminal alpha-helix does not alter the secondary structure of the protein
      but amplifies the interaction with membranes significantly, indicating that p6
      binds to the polar head groups at the surface of the cytoplasmic membrane. The
      increased hydrophobic membrane interaction of p6(23-52) S40F correlated with the
      observed increased amount of the polyprotein Gag in the RIPA insoluble fraction
      when Ser40 of p6 was mutated with Phe indicating that p6 modulates the membrane
      interactions of HIV-1 Gag.

PMID- 23174351
TI  - Structure and dynamics of the two amphipathic arginine-rich peptides RW9 and RL9
      in a lipid environment investigated by solid-state NMR and MD simulations.
AB  - Cell penetrating peptides (CPPs) are able to cross membranes without using
      receptors but only little information about the underlying mechanism is
      available. In this work, we investigate the interaction of the two arginine-rich
      CPPs RW9 and RL9 with 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphatidylcholine
      (POPC), 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphatidylglycerol (POPG), and
      POPC/POPG membranes with varying POPG content using isothermal titration
      calorimetry (ITC), solid-state nuclear magnetic resonance (NMR) spectroscopy, and
      molecular dynamics (MD) simulations. Both peptides were derived from the known
      CPP penetratin and it was shown previously that RW9 is able to penetrate
      membranes better than RL9. Overall, the results show that both RW9 and RL9 have a
      relatively small influence on the membrane. They increase the order of the lipids
      in the headgroup region and reduce order in the acyl chains indicating that they
      are located in the lipid/water interface. In addition, the flexibility of the
      membrane is slightly increased by both peptides but RW9 has a larger influence
      than RL9. The differences observed in the influences on POPC and POPG as well as
      MD simulations on the mixed POPC/POPG bilayers of 850ns length each show that
      both peptides preferentially associate with and enrich the charged PG lipids
      almost 2fold in an area of 12A around the peptides. As expected, we could not
      observe any membrane crossing on the simulation time scale of 850ns but observed
      that some peptides flipped their orientation during binding to the membrane.
      Interestingly, all observed flips coincided with structural changes in the
      peptides indicating that structural changes or flexibility might play a role
      during the binding of arginine-rich CPPs to membranes.

PMID- 23174352
TI  - Transport and uptake of immunogenic lipids.
AB  - An increasing number of lipid mediators have been identified as key modulators of
      immunity. Among these is a family of glycolipids capable of cellular uptake,
      loading onto the MHC-like molecule CD1d and stimulation of NKT cells. NKT cells
      are particularly interesting because they bridge innate and adaptive immunity by
      coordinating the early events of dendritic cell maturation, recruitment of NK
      cells, CD4 and CD8 T cells, and B cells at the site of microbial injury. As such,
      their therapeutic manipulation could be of the greatest interest in vaccine
      design or active immunotherapy. However, the use of NKT cells as cellular
      adjuvant of immunity in the clinic will require a better knowledge of the
      pharmacology of lipid agonists in order to optimize their action and avoid
      potential unseen off-target effects. We have been studying extracellular
      transport and cellular uptake of NKT agonists for the past few years. This field
      is confronted to a very limited prior knowledge and a small set of usable tools.
      New technology must be put in place and adapted to answering basic immunology
      questions related to NKT cells. The intimate link between the pharmacology of
      glycolipids and lipid metabolism makes us believe that great variations of
      bioactivity could be seen in the general population when NKT agonists are used
      therapeutically.

PMID- 23174353
TI  - Management considerations for malignant tumors of the skull base.
AB  - The last two decades have brought refinements in diagnostic imaging,
      instrumentation, and microvascular reconstruction, and an improved overall
      appreciation of the anatomy of the skull base, both open and endoscopic. These
      refinements have extended the boundaries of tumor resection and have obviated
      adjuvant therapies in some patients with benign or low-grade tumors. In patients
      with high-grade malignancies, however, a carefully constructed multimodal
      treatment plan, incorporating surgery, radiation therapy, and chemotherapy, is
      necessary to maximize patients' outcomes.

PMID- 23174354
TI  - Anterior and anterolateral resection for skull base malignancies: techniques and
      complication avoidance.
AB  - Combined anterior cranial base resection is the mainstay of therapy for skull
      base malignancies. Improvements in surgical techniques and reconstruction have
      led to a reduction in morbidity and overall better survival rates. Meticulous
      attention to dural and skull base reconstruction is essential for reducing the
      major complications, including cerebrospinal fluid leak and pneumocephalus.
      Complications can be devastating, but timely effective management can limit the
      severity.

PMID- 23174355
TI  - Minimally invasive approaches to the anterior skull base.
AB  - The use of minimally invasive approaches to the anterior skull base is a valuable
      tool to improving the treatment in patients with aggressive anterior skull base
      neoplasms. This article discusses the history, advantages and disadvantages
      relative to open approaches, the corridors and pathways used in approach, the
      equipment and operating room setup, perioperative care, and complication
      avoidance. Although outcomes are difficult to compare to open approaches, due to
      often small and varying patient cohorts, these approaches continue to gain
      acceptance as an effective treatment of anterior skull base tumors in the
      experienced surgeon's hands with proper patient selection.

PMID- 23174356
TI  - Sinonasal carcinomas: epidemiology, pathology, and management.
AB  - Sinonasal carcinomas are uncommon neoplasms accounting for approximately 3% to 5%
      of all upper respiratory tract malignancies. Sinonasal malignancies in most cases
      do not cause early symptoms and present in an advanced stage of disease. Exact
      staging necessitates a clinical and endoscopic examination with biopsy and
      imaging. Tumor resection using an open or endoscopic approach is usually
      considered the first treatment option. In general, sinonasal carcinomas are
      radiosensitive, so adjuvant or neoadjuvant radiation treatment may be indicated
      in advanced disease. Multidisciplinary surgical and medical oncologic approaches,
      including ablation and reconstruction, have enhanced the survival outcome over
      the past few decades.

PMID- 23174357
TI  - Esthesioneuroblastoma.
AB  - Esthesioneuroblastoma is a rare malignant neoplasm in the olfactory region of the
      nasal cavity and anterior skull base. Diagnosis and staging require anatomic
      imaging and careful pathologic assessment. Standard treatment is anterior
      craniofacial resection with postoperative irradiation. The role for chemotherapy
      is not defined, but is generally for the most advanced cases and used in the
      neoadjuvant setting and/or postoperatively with irradiation. Prognosis is
      favorable; however, metastasis rates remain relatively high. Regional and distant
      metastasis portends a poor outcome. Intensity-modulated radiation treatment and
      endoscopic surgery have reduced morbidity, but outcomes with these techniques
      must be fully evaluated.

PMID- 23174358
TI  - Head and neck sarcomas: epidemiology, pathology, and management.
AB  - Sarcomas of the head, neck, and skull base represent a heterogeneous group of
      tumors with distinct prognostic features. There have been significant
      improvements in characterizing these sarcomas using traditional morphologic
      assessments and more recent immunohistochemical analysis. Surgery is the mainstay
      of treatment followed by radiation therapy. Treatment modalities have changed in
      select pediatric sarcomas, for which new chemotherapeutic combinations have
      improved survival statistics. The high rate of distant failure emphasizes the
      need for novel systemic and directed molecular therapies. Tumor grade, size, and
      margin status are key factors in survival.

PMID- 23174359
TI  - Skull base chordomas: clinical features, prognostic factors, and therapeutics.
AB  - Chordomas of the skull base are one of the rarest intracranial malignancies that
      arise from ectopic remnants of embryonal notochod. The proximity of many
      chordomas to neurovascular structures makes gross total resection difficult, and
      the tendency for recurrence leads to the routine use of adjuvant postoperative
      radiation. Several surgical approaches are used ranging from extensive
      craniotomies to minimally invasive endonasal endoscopic approaches. In this
      review, the histopathology and epidemiology, imaging characteristics, surgical
      approaches, adjuvant therapies, prognostic factors, and molecular biology of
      chordomas are described.

PMID- 23174360
TI  - Skull base chondrosarcoma: evidence-based treatment paradigms.
AB  - Chondrosarcomas are indolent but invasive chondroid malignancies that can form in
      the skull base. Standard management of chondrosarcoma involves surgical resection
      and adjuvant radiation therapy. This review evaluates evidence from the
      literature to assess the importance of the surgical approach and extent of
      resection on outcomes for patients with skull base chondrosarcoma. Also evaluated
      is the ability of the multiple modalities of radiation therapy, such as
      conventional fractionated radiotherapy, proton beam, and stereotactic
      radiosurgery, to control tumor growth. Finally, emerging therapies for the
      treatment of skull-base chondrosarcoma are discussed.

PMID- 23174361
TI  - Temporal bone malignancies.
AB  - Primary temporal bone tumors are rare. Suspicious lesions of the ear canal should
      be biopsied for diagnosis. Surgical resection to achieve negative margins is the
      mainstay of treatment. Small tumors can be treated with lateral temporal bone
      resection. Parotidectomy and neck dissection are added for disease extension and
      proper staging. Higher staged tumors generally require subtotal temporal bone
      resection or total temporal bone resection. Adjuvant postoperative radiotherapy
      has shown improved survival for some patients. Chemotherapy has an emerging role
      for advanced stage disease. Evaluation and management by a multidisciplinary team
      are the best approach for patients with these tumors.

PMID- 23174362
TI  - Craniofacial reconstruction following oncologic resection.
AB  - The ability to reliably reconstruct complex and sizable wounds has decreased the
      morbidity of skull base surgery substantially, preventing major complications and
      allowing treatment of tumors previously considered inoperable. Addressing facial
      nerve function with static and dynamic procedures as well as fabrication of
      craniofacial prostheses to replace delicate facial landmarks has further
      increased surgeons' ability to restore the appearance and function of the face.

PMID- 23174363
TI  - Radiotherapy for malignant tumors of the skull base.
AB  - Malignant tumors of the skull base are a fascinating group of tumors arising via
      disparate causes leading often to similar presentations. This article explores
      radiotherapy techniques applied to this group of malignancies, with a focus on
      providing general overview and guiding readers to primary sources to achieve
      greater depth. The outcomes and effects of radiation, therapeutic radiation
      modalities and delivery system are discussed. Equipped with these basic
      principles, practitioners will have general guidance for rational treatment
      modality selection for patients with skull base tumors.

PMID- 23174364
TI  - Malignant tumors of the skull base. Preface.

PMID- 23174365
TI  - [Candida peritonitis: Prevalence and risk factors].
AB  - BACKGROUND: A peritoneal fluid with a positive culture for Candida in patients
      with associated clinical symptoms enables peritoneal candidiasis (PC) to be
      diagnosed. This etiology is related to a poor prognosis, thus, it is important to
      know all the risk factors and to start early an empirical treatment. The risk
      factors associated with this kind of peritonitis are to receive prolonged
      antibiotic treatment, nosocomial infection, female gender, involvement of the
      upper gastro-intestinal (UGI) tract, and the ocurrence of an intraoperative
      cardiovascular failure (CVF). AIMS: The principal aim was to determine the
      prevalence of PC in our hospital, and the secondary aims to determine the
      associated risk factors. METHODS: We obtained samples from 74 patients diagnosed
      with peritonitis, consecutively from 2007 to 2010. Cultures were performed with
      the free peritoneal fluid aspirated during surgery. RESULTS: The prevalence of PC
      obtained in our hospital was 17.6%, from which 46.15% corresponded to Candida
      albicans. The involvement of the UGI tract and the onset of CVF can be considered
      risk factors for the development of this pathology. Age, gender, nosocomial
      infection and previous antibiotic treatment were not related to this pathology.
      CONCLUSIONS: Our prevalence of PC is 17.6%. The risk factors that could
      predispose are the involvement of the UGI tract as the cause of peritonitis, and
      CVF during surgical procedure.

PMID- 23174366
TI  - ABCC5 supports osteoclast formation and promotes breast cancer metastasis to
      bone.
AB  - INTRODUCTION: Bone is the most common site of breast cancer metastasis, and
      complications associated with bone metastases can lead to a significantly
      decreased patient quality of life. Thus, it is essential to gain a better
      understanding of the molecular mechanisms that underlie the emergence and growth
      of breast cancer skeletal metastases. METHODS: To search for novel molecular
      mediators that influence breast cancer bone metastasis, we generated gene
      expression profiles from laser-capture microdissected trephine biopsies of both
      breast cancer bone metastases and independent primary breast tumors that
      metastasized to bone. Bioinformatics analysis identified genes that are
      differentially expressed in breast cancer bone metastases compared with primary,
      bone-metastatic breast tumors. RESULTS: ABCC5, an ATP-dependent transporter, was
      found to be overexpressed in breast cancer osseous metastases relative to primary
      breast tumors. In addition, ABCC5 was significantly upregulated in human and
      mouse breast cancer cell lines with high bone-metastatic potential. Stable
      knockdown of ABCC5 substantially reduced bone metastatic burden and osteolytic
      bone destruction in mice. The decrease in osteolysis was further associated with
      diminished osteoclast numbers in vivo. Finally, conditioned media from breast
      cancer cells with reduced ABCC5 expression failed to induce in vitro
      osteoclastogenesis to the same extent as conditioned media from breast cancer
      cells expressing ABCC5. CONCLUSIONS: Our data suggest that ABCC5 functions as a
      mediator of breast cancer skeletal metastasis. ABCC5 expression in breast cancer
      cells is important for efficient osteoclast-mediated bone resorption. Hence,
      ABCC5 may be a potential therapeutic target for breast cancer bone metastasis.

PMID- 23174367
TI  - Phylogeny and biogeography of highly diverged freshwater fish species
      (Leuciscinae, Cyprinidae, Teleostei) inferred from mitochondrial genome analysis.
AB  - The distribution of freshwater taxa is a good biogeographic model to study
      pattern and process of vicariance and dispersal. The subfamily Leuciscinae
      (Cyprinidae, Teleostei) consists of many species distributed widely in Eurasia
      and North America. Leuciscinae have been divided into two phyletic groups,
      leuciscin and phoxinin. The phylogenetic relationships between major clades
      within the subfamily are poorly understood, largely because of the overwhelming
      diversity of the group. The origin of the Far Eastern phoxinin is an interesting
      question regarding the evolutionary history of Leuciscinae. Here we present
      phylogenetic analysis of 31 species of Leuciscinae and outgroups based on
      complete mitochondrial genome sequences to clarify the phylogenetic relationships
      and to infer the evolutionary history of the subfamily. Phylogenetic analysis
      suggests that the Far Eastern phoxinin species comprised the monophyletic clades
      Tribolodon, Pseudaspius, Oreoleuciscus and Far Eastern Phoxinus. The Far Eastern
      phoxinin clade was independent of other Leuciscinae lineages and was closer to
      North American phoxinins than European leuciscins. All of our analysis also
      suggested that leuciscins and phoxinins each constituted monophyletic groups.
      Divergence time estimation suggested that Leuciscinae species diverged from
      outgroups such as Tincinae to be 83.3 million years ago (Mya) in the Late
      Cretaceous and leuciscin and phoxinin shared a common ancestor 70.7 Mya.
      Radiation of Leuciscinae lineages occurred during the Late Cretaceous to
      Paleocene. This period also witnessed the radiation of tetrapods. Reconstruction
      of ancestral areas indicates Leuciscinae species originated within Europe.
      Leuciscin species evolved in Europe and the ancestor of phoxinin was distributed
      in North America. The Far Eastern phoxinins would have dispersed from North
      America to Far East across the Beringia land bridge. The present study suggests
      important roles for the continental rearrangements during the Late Cretaceous to
      form the present-day distribution of organisms. Furthermore, the Late Cretaceous
      biotic turnover influenced for the modern terrestrial biodiversity.

PMID- 23174368
TI  - Niacin improves lipid profile but not endothelial function in patients with
      coronary artery disease on high dose statin therapy.
AB  - AIMS: To determine the effect of extended release (ER) niacin on endothelial and
      vascular function assessed by brachial flow-mediated dilatation (FMD), peak
      hyperemic velocity (VTiRH) and pulse arterial tonometry (PAT) in patients with
      established coronary artery disease (CAD), already treated with high dose
      statins. Endothelial dysfunction is common in patients with established coronary
      artery disease (CAD) and has prognostic implications. Niacin has proven clinical
      benefit in patients with CAD, but its additive effect in patients on statin
      therapy is being evaluated. The effect of niacin on endothelial function, in the
      presence of optimal LDL cholesterol is unclear. METHODS AND RESULTS: Sixty-six
      patients with CAD (mean age 57.9 +/- 8.5 yrs) received ER niacin (1500 mg per
      day) and placebo in a randomized crossover fashion for 3 months of each therapy.
      All patients received atorvastatin 80 mg per day. FMD, VTiRH and PAT measurements
      were performed at baseline and after each treatment period. Treatment with niacin
      improved dyslipidemia parameters (LDL placebo 1.52 +/- 0.51 vs. niacin 1.30 +/-
      0.43; p = 0.004; HDL placebo 0.95 +/- 0.16 vs. niacin 1.11 +/- 0.22; p < 0.001).
      However, there was no observed improvement in endothelial function as assessed by
      FMD (placebo 6.1 +/- 4.9 vs. niacin 6.6 +/- 4.8%; p = 0.48), VTiRH (placebo 75 +/
      28 vs. niacin 78 +/- 26 cm; p = 0.23) or PAT (placebo 1.8 +/- 0.42 vs. niacin
      1.79 +/- 0.5; p = 0.43). CONCLUSION: Niacin as add-on treatment to high dose
      statins in patients with established CAD significantly improves lipid profile.
      However, these changes were not associated with improved endothelial or
      microvascular function. Registered clinical trial with clinicaltrials.gov:
      NCT00150722.

PMID- 23174369
TI  - Effects of pitavastatin and atorvastatin on lipoprotein oxidation biomarkers in
      patients with dyslipidemia.
AB  - OBJECTIVE: The effects of potent statins on oxidized lipoprotein biomarkers are
      not well defined. METHODS AND RESULTS: The VISION (Value of oxIdant lipid
      lowering effect by Statin InterventiON in hypercholesterolemia) Trial randomized
      patients with hypercholesterolemia to 12-week administration of pitavastatin 2
      mg/day (n = 21) or atorvastatin 10 mg/day (n = 21) and a variety of lipoprotein
      oxidative biomarkers were measured. Between-group analysis did not reveal any
      differences except in the ratio of malondialdehyde (MDA)-LDL over apolipoprotein
      B-100 (MDA-LDL/apoB) in pitavastatin vs. atorvastatin group (-13% vs. -0.7%, p =
      0.04). Within-group changes from baseline to 12-week revealed significant
      increases in OxPL/apoB and reductions in small-dense LDL, MDA-LDL, and
      lipoprotein-associated phospholipase A(2) measured on circulating apoB particles
      (Lp-PLA(2)/apoB) in both groups and significant reductions in OxPL/apoAI in the
      atorvastatin group. CONCLUSIONS: The VISION study describes the first comparison
      on lipoprotein oxidation biomarkers between pitavastatin and atorvastatin and
      suggests diverse effects on lipoprotein oxidation markers in patients with
      hypercholesterolemia.

PMID- 23174370
TI  - Co-culture embedded in cumulus clumps promotes maturation of denuded oocytes and
      reconstructs gap junctions between oocytes and cumulus cells.
AB  - The present study was undertaken to establish an effective method for in vitro
      maturation (IVM) of denuded oocytes (DOs) by simulating the ovarian three
      dimensional status in vivo using buffalo ovarian tissues or cumulus cells, so as
      to provide a model for investigating the mechanisms of oocyte maturation. Buffalo
      cumulus-oocyte complexes from ovaries taken at slaughter were denuded by
      pipetting, and then allocated randomly into four groups for IVM by direct culture
      in maturation medium (M1, control group), co-culture with a monolayer of cumulus
      cells (M2), embedded in cumulus cell clumps (M3) and ovarian tissue (M4) for 24
      h. The nuclear maturation of DOs was assessed by the extrusion of the first polar
      body and the cytoplasmic maturation was evaluated by subsequently developmental
      capacity after parthenogenetic activation. More DOs matured to MII (56.89%) and
      developed to blastocysts (25.75%) when they were matured in vitro with M3 in
      comparison with DOs matured in vitro with M1 (45.14 and 15.97%) and M4 (40.48 and
      13.49%). Further detection of gap junctions by injecting Lucifer yellow directly
      into cytoplasm of matured DOs with adherent cumulus cells and scanning with
      confocal microscope showed that Lucifer yellow were found in nine out of 11 the
      adherent cumulus cells in M3, indicating that the gap junctions between oocytes
      and cumulus cells was reconstructed in vitro. These results indicate that co
      culture of DOs embedded in cumulus cell clumps can improve their nuclear and
      cytoplasmic maturation of DOs, possibly through the reconstruction of gap
      junctions in vitro.

PMID- 23174371
TI  - Prion diseases remain a mystery.

PMID- 23174372
TI  - Human microbial challenge: the ultimate animal model.

PMID- 23174373
TI  - Effect of intermittent preventative therapy for secondary prevention of severe
      malarial anaemia.

PMID- 23174375
TI  - Public-private mix in tuberculosis.

PMID- 23174376
TI  - Public-private mix in tuberculosis.

PMID- 23174377
TI  - Public-private mix in tuberculosis.

PMID- 23174378
TI  - Public-private mix in tuberculosis - Authors' reply.

PMID- 23174380
TI  - Pretreatment HIV-1 drug resistance testing in sub-Saharan Africa.

PMID- 23174381
TI  - The burden of tuberculosis in crisis-affected populations: a systematic review.
AB  - Crises caused by armed conflict, forced population displacement, or natural
      disasters result in high rates of excess morbidity and mortality from infectious
      diseases. Many of these crises occur in areas with a substantial tuberculosis
      burden. We did a systematic review to summarise what is known about the burden of
      tuberculosis in crisis settings. We also analysed surveillance data from camps
      included in UN High Commissioner for Refugees (UNHCR) surveillance, and
      investigated the association between conflict intensity and tuberculosis
      notification rates at the national level with WHO data. We identified 51 reports
      of tuberculosis burden in populations experiencing displacement, armed conflict,
      or natural disaster. Notification rates and prevalence were mostly elevated;
      where incidence or prevalence ratios could be compared with reference
      populations, these ratios were 2 or higher for 11 of 15 reports. Case-fatality
      ratios were mostly below 10% and, with exceptions, drug-resistance levels were
      comparable to those of reference populations. A pattern of excess risk was noted
      in UNHCR-managed camp data where the rate of smear testing seemed to be
      consistent with functional tuberculosis programmes. National-level data suggested
      that conflict was associated with decreases in the notification rate of
      tuberculosis. More studies with strict case definitions are needed in crisis
      settings, especially in the acute phase, in internally displaced populations and
      in urban settings. Findings suggest the need for early establishment of
      tuberculosis services, especially in displaced populations from high-burden areas
      and for continued innovation and prioritisation of tuberculosis control in crisis
      settings.

PMID- 23174384
TI  - [Does the sickle cell trait (heterozygous carrier status) confer protection
      against malaria?].
AB  - The high frequency of the gene for sickle-cell hemoglobin in malaria-endemic
      regions is believed to be due to an advantage in surviving malaria. We report the
      case of a woman with both malaria and hemoglobin S.

PMID- 23174382
TI  - Strategies to increase responsiveness to hepatitis B vaccination in adults with
      HIV-1.
AB  - HIV and hepatitis B virus co-infection leads to substantially increased morbidity
      and mortality compared with either infection alone. Immunisation with hepatitis B
      virus vaccine is the most effective way to prevent the infection in people with
      HIV; however, these patients have decreased vaccine responses and a short
      duration of protection compared with immunocompetent individuals. Control of HIV
      replication with highly active antiretroviral therapy and increased CD4 cell
      counts are associated with improved immune responses to hepatitis B vaccination.
      New vaccination strategies, such as increased vaccine dose, use of the
      intradermal route, and addition of adjuvants, could improve response rates in
      adults with HIV.

PMID- 23174385
TI  - Perception of front-of-pack labels according to social characteristics,
      nutritional knowledge and food purchasing habits.
AB  - OBJECTIVE: To identify patterns of perception of front-of-pack (FOP) nutrition
      labels and to determine social factors, nutritional knowledge and attention to
      packaging features related to such patterns. DESIGN: Cross-sectional. Perception
      was measured using indicators of understanding and acceptability of three simple
      FOP labels (the 'Green Tick', the logo of the French Nutrition and Health
      Programme (PNNS logo) and 'simple traffic lights' (STL)) and two detailed formats
      ('multiple traffic lights' (MTL) and the 'colour range' logo (CR)). Associations
      of perception patterns with individual characteristics were examined using chi2
      tests. SETTING: Data from the French NutriNet-Sante cohort study. SUBJECTS: A
      total of 38,763 adults. RESULTS: Four perception patterns emerged. Poorly
      educated individuals were most often found in groups favouring simple formats.
      The 'favourable to CR' group had a high rate of men and older persons. Poor
      nutritional knowledge was more frequent in the 'favourable to STL' group, while
      individuals with substantial knowledge were proportionally more numerous in the
      'favourable to MTL' group. The 'favourable to STL' group more frequently self
      reported noting price and marketing characteristics during purchasing, while the
      'favourable to MTL' and 'favourable to CR' groups declared more interest in
      nutritional information. The 'favourable to Green Tick and PNNS logo' group self
      reported paying closer attention to claims and quality guarantee labels.
      CONCLUSIONS: The 'favourable to MTL' cluster was most frequently represented in
      our survey. However, simple FOP formats may be most appropriate for increasing
      awareness of healthy eating among targeted groups with poor nutritional knowledge
      and little interest in the nutritional quality of packaged foods.

PMID- 23174386
TI  - Oxytocin use during active labor: too much of a good thing?

PMID- 23174383
TI  - Lessons from malaria control to help meet the rising challenge of dengue.
AB  - Achievements in malaria control could inform efforts to control the increasing
      global burden of dengue. Better methods for quantifying dengue endemicity
      equivalent to parasite prevalence surveys and endemicity mapping used for malaria
      would help target resources, monitor progress, and advocate for investment in
      dengue prevention. Success in controlling malaria has been attributed to
      widespread implementation of interventions with proven efficacy. An improved
      evidence base is needed for large-scale delivery of existing and novel
      interventions for vector control, alongside continued investment in dengue drug
      and vaccine development. Control of dengue is unlikely to be achieved without
      coordinated international financial and technical support for national
      programmes, which has proven effective in reducing the global burden of malaria.

PMID- 23174387
TI  - The association between hospital obstetric volume and perinatal outcomes in
      California.
AB  - OBJECTIVE: We sought to analyze the association between hospital obstetric volume
      and perinatal outcomes in California. STUDY DESIGN: This was a retrospective
      cohort study of births occurring in California in 2006. Hospitals were divided
      into 4 obstetric volume categories. Unadjusted rates of neonatal mortality and
      birth asphyxia were calculated for each category, overall and among term
      deliveries with birthweight >2500 g. Multivariable logistic regression was used
      to control for confounders. Deliveries in rural hospitals were analyzed
      separately using different volume categories. RESULTS: Prevalence of asphyxia
      increased with decreasing hospital volume overall and among term, non-low
      birthweight infants, from 9/10,000 live births at highest-volume hospitals to
      18/10,000 live births at the lowest-volume hospitals (P < .001). Similar trends
      were observed in rural hospitals, with rates increasing from 7-34/10,000 live
      births in low-volume rural hospitals (P < .001). CONCLUSION: These findings
      provide evidence for an inverse association between hospital obstetric volume and
      birth asphyxia.

PMID- 23174389
TI  - Role of faith-based and nongovernment organizations in the provision of obstetric
      services in 3 African countries.
AB  - OBJECTIVE: We sought to describe obstetric care capacity of nongovernment
      organization (NGO)-/faith-based organization (FBO)-run institutions compared to
      government-run institutions in 3 African countries using the World Health
      Organization Global Survey. We also compared delivery characteristics and
      outcomes. STUDY DESIGN: This is a descriptive analysis of the 22 NGO-/FBO-run
      institutions in Uganda, Kenya and Democratic Republic of Congo delivering 11,594
      women, compared to 20 government-run institutions delivering 25,825 women in the
      same countries and period. RESULTS: Infrastructure, obstetric services,
      diagnostic facilities, and anesthesiology at NGO/FBO institutions were comparable
      to government institutions. Women delivering at NGO/FBO institutions had more
      antenatal care, antenatal complications, and cesarean delivery. NGO/FBO
      institutions had higher obstetrician attendance and lower rates of eclampsia,
      preterm birth, stillbirth, Apgar <7, and neonatal near miss. CONCLUSION: NGO/FBO
      institutions are comparable to government institutions in capacity to deliver
      obstetric care. NGO/FBOs have been found effective in providing delivery care in
      developing countries and should be appropriately recognized by stakeholders in
      their efforts to assist nations achieve international goals.

PMID- 23174388
TI  - Obesity trends and perinatal outcomes in black and white teenagers.
AB  - OBJECTIVE: Our objective was to explore the trends in prepregnancy body mass
      index (BMI) for black and white teenagers over time and the association between
      elevated BMI and outcomes based on race. STUDY DESIGN: This was a retrospective
      cohort study of singleton infants (n = 38,158) born to black (34%) and white
      (66%) teenagers (<18 years of age). We determined the prevalence of elevated
      prepregnancy BMI between 1993 and 2006 and the association between elevated
      prepregnancy BMI (primary exposure) and maternal and perinatal outcomes based on
      race (2000-2006). RESULTS: The percentage of white teenagers with elevated
      prepregnancy BMI increased significantly from 17-26%. White and black overweight
      and obese teenagers were more likely to have pregnancy-related hypertension than
      normal-weight teenagers; postpartum hemorrhage was increased only in obese black
      teenagers, and infant complications were increased only in overweight and obese
      white teenagers. CONCLUSION: Because the percentage of elevated prepregnancy BMI
      has increased in white teenagers, specific risks for poor maternal and perinatal
      outcomes in the overweight and obese teenagers varies by race.

PMID- 23174390
TI  - Neuroprotective peptides influence cytokine and chemokine alterations in a model
      of fetal alcohol syndrome.
AB  - OBJECTIVE: Fetal alcohol syndrome (FAS) is associated with intellectual
      disability and neurodevelopmental abnormalities. Neuroprotective peptides
      NAPVSIPQ (NAP) and SALLRSIPA (SAL) can prevent some of the alcohol-induced
      teratogenesis including fetal death, growth abnormalities, and learning
      impairment in part by preventing alcohol-induced alterations in N-methyl-D
      aspartate receptor gene expression in a mouse model for FAS. We evaluated a panel
      of cytokines and chemokines to determine whether NAP plus SAL work through a
      cytokine/chemokine-mediated pathway in preventing these alterations. STUDY
      DESIGN: Using a well-characterized FAS model, timed, pregnant C57BL6/J mice were
      treated on gestational day (E) 8 with alcohol (0.03 mL/g), placebo, or alcohol
      plus peptides. Embryos were evaluated at 2 time points: after 6 hours and 10 days
      later at E18. A panel of cytokines/chemokines was measured using a microsphere
      based multiplex immunoassay (Luminex xMAP; Millipore, Billerica, MA). Statistical
      analysis included Kruskal-Wallis, with P < .05 considered significant. RESULTS:
      Six hours after treatment, interleukin (IL)-6 and keratinocyte chemoattractant
      cytokine (KC) were not detectable in the control embryos. Alcohol treatment
      resulted in detectable levels and significant increases in IL-6 (median, 15.7;
      range, 10.1-45.9 pg/mL) and KC (median, 45.9; range, 32.5-99.1 pg/mL). Embryos
      exposed to alcohol plus NAP plus SAL had undetectable IL-6 and KC (both P <
      .003), similar to the controls. Alcohol exposure resulted in a significant
      increase of granulocyte colony-stimulating factor (G-CSF) (P < .003) as compared
      with controls, and treatment with NAP plus SAL prevented the alcohol-induced
      increase. IL-13 and IL-1beta were decreased 6 hours after alcohol exposure, and
      exposure to alcohol plus NAP plus SAL did not completely ameliorate the decrease.
      At E18, 10 days after exposure, these alterations were no longer present. Several
      analytes (regulated upon activation, normal T cell expressed, and secreted, tumor
      necrosis factor-alpha, interferon-gamma, and IL-4) were not detectable at either
      time point in any of the groups. CONCLUSION: Prenatal alcohol exposure acutely
      results in a significant elevation of IL-6, G-CSF and the KC, which are known to
      affect N-methyl-D-aspartate receptors. NAP plus SAL treatment prevented alcohol
      induced increases. This provides additional insight into the mechanism of alcohol
      damage in FAS and NAP plus SAL prevention of neurodevelopmental anomalies.

PMID- 23174391
TI  - Performance of an automatic quantitative ultrasound analysis of the fetal lung to
      predict fetal lung maturity.
AB  - OBJECTIVE: The objective of the study was to evaluate the performance of
      automatic quantitative ultrasound analysis (AQUA) texture extractor to predict
      fetal lung maturity tests in amniotic fluid. STUDY DESIGN: Singleton pregnancies
      (24.0-41.0 weeks) undergoing amniocentesis to assess fetal lung maturity (TDx
      fetal lung maturity assay [FLM]) were included. A manual-delineated box was
      placed in the lung area of a 4-chamber view of the fetal thorax. AQUA transformed
      the information into a set of descriptors. Genetic algorithms extracted the most
      relevant descriptors and then created and validated a model that could
      distinguish between mature or immature fetal lungs using TDx-FLM as a reference.
      RESULTS: Gestational age at enrollment was (mean [SD]) 32.2 (4.5) weeks.
      According to the TDx-FLM results, 41 samples were mature and 62 were not. The
      imaging biomarker based on AQUA presented a sensitivity 95.1%, specificity 85.7%,
      and an accuracy 90.3% to predict a mature or immature lung. CONCLUSION: Fetal
      lung ultrasound textures extracted by AQUA provided robust features to predict
      TDx-FLM results.

PMID- 23174392
TI  - Comparative transplacental transfer of taxanes using the human perfused cotyledon
      placental model.
AB  - OBJECTIVES: The use of taxanes (paclitaxel and docetaxel) in pregnant cancer
      patients is increasing. We aimed to compare their transplacental transfer using
      the gold standard human placental perfusion model, to guide drug selection. STUDY
      DESIGN: Term placentas were perfused with paclitaxel or docetaxel and 2 different
      albumin concentrations. Main transfer parameters such as fetal transfer rate
      (FTR), clearance index, and placental uptake of taxanes were assessed. RESULTS:
      Twelve placentas were perfused, 6 with paclitaxel and 6 with docetaxel. Mean FTR
      of paclitaxel decreased significantly from 5.67 +/- 0.02% in low albumin
      conditions to 1.72 +/- 0.09% in physiological albumin conditions. Similarly, mean
      clearance index decreased significantly from 0.22 +/- 0.02 to 0.09 +/- 0.01.
      Regarding docetaxel, mean FTR were similar in low albumin and physiological
      conditions (5.03 +/- 0.60% and 4.04 +/- 0.22%, respectively) while mean clearance
      index decreased significantly from 0.18 +/- 0.02 to 0.13 +/- 0.01. Taxanes
      accumulation in cotyledon was similar for docetaxel and paclitaxel: 4.54 +/-
      1.84% vs 3.31 +/- 1.88%, respectively. CONCLUSION: Transplacental transfer and
      placental accumulation of paclitaxel and docetaxel were low and similar,
      especially in physiological conditions of albumin. Further studies are warranted
      to optimize the selection of a taxane in pregnant cancer patients.

PMID- 23174394
TI  - The role of cognitive functioning in the outcome of those at clinical high risk
      for developing psychosis.
AB  - Although it is well established that cognitive impairment is a common feature of
      schizophrenia, only recently has cognitive functioning been prospectively studied
      in individuals at clinical high risk (CHR) for developing psychosis. To date,
      both cross-sectional and longitudinal studies have been conducted in the CHR
      population and in the context of later conversion to psychosis. A comprehensive
      review of the literature suggests that CHR individuals have general and specific
      baseline cognitive deficits compared to healthy controls. As a group, their
      cognitive course, tends to remain stable over time and in this way does not
      differ from healthy controls. For those who go on to develop a full-blown
      psychotic illness compared to those who do not convert, there appeared to be
      minimal differences at baseline with respect to cognition, although over time the
      converters may show deterioration in certain cognitive abilities compared to the
      non-converters. However, for many cognitive domains results are mixed, and may
      result from methodological limitations.

PMID- 23174395
TI  - Prismatic correction of consecutive esotropia in children after a unilateral
      recession and resection procedure.
AB  - PURPOSE: To determine the long-term efficacy of prismatic correction in
      consecutive esotropia after a unilateral recession and resection (RR) procedure
      for primary exotropia. DESIGN: Retrospective cohort study. PARTICIPANTS: A total
      of 110 patients with esodeviation of 5 prism diopters (PD) or more at 4 weeks
      after the unilateral RR procedure for primary exotropia who were fitted with
      prism glasses and were followed up for a minimum of 2 years after primary
      surgery. METHODS: Patients were divided into 2 groups based on whether they were
      weaned off the prism glasses within 1 year: (1) the prism-weaned group whose
      esotropia decreased enough for them to be weaned off the prism within 1 year; (2)
      the prism-wearing group who wore prism glasses for more than 1 year. Clinical
      characteristics and changes in deviation angle were compared between groups. MAIN
      OUTCOME MEASURES: The period of prism wearing, the rate of decline in deviation
      angle after prismatic correction, and preoperative and postoperative motor and
      sensory outcomes. RESULTS: The average age of patients was 4.7 years. Overall,
      the average period of prism wearing was 20.9 months, and the rate of decrease in
      the deviation angle was 2.9 PD per 6 months. Thirty-four patients (32%) were
      weaned off the prism glasses within 1 year. The prism-weaned group showed more
      preoperative constant deviation and anisometropia compared with the prism-wearing
      group. Overall, successful motor outcome was achieved in 71% of patients. The
      rate of recurrence during follow-up was higher in the prism-weaned group, and the
      rate of overcorrection was higher in the prism-wearing group (P = 0.003). No
      patients demonstrated new onset amblyopia, and 1 of the 105 patients (0.95%)
      demonstrated loss of stereoacuity as a result of overcorrection. At the final
      visit, stereoacuity was improved or was maintained in 92% of patients compared
      with preoperative values. CONCLUSIONS: Prismatic correction can lead to good
      motor outcomes while maintaining favorable sensory status in most patients with
      consecutive esotropia. Patients showed different clinical manifestations and
      outcome according to the period of prismatic correction. Patients in the prism
      weaned group showed a faster change in esodeviation after prismatic correction
      and more exotropic drift after prism weaning, resulting in a higher rate of
      recurrence of exotropia.

PMID- 23174396
TI  - Femtosecond lasers for LASIK flap creation: a report by the American Academy of
      Ophthalmology.
AB  - OBJECTIVE: To review the published literature to assess the safety, efficacy, and
      predictability of femtosecond lasers for the creation of corneal flaps for LASIK;
      to assess the reported outcomes of LASIK when femtosecond lasers are used to
      create corneal flaps; and to compare the differences in outcomes between
      femtosecond lasers and mechanical microkeratomes. METHODS: Literature searches of
      the PubMed and Cochrane Library databases were last conducted on October 12,
      2011, without language or date limitations. The searches retrieved a total of 636
      references. Of these, panel members selected 58 articles that they considered to
      be of high or medium clinical relevance, and the panel methodologist rated each
      article according to the strength of evidence. Four studies were rated as level I
      evidence, 14 studies were rated as level II evidence, and the remaining studies
      were rated as level III evidence. RESULTS: The majority of published studies
      evaluated a single laser platform. Flap reproducibility varied by device and the
      generation of the device. Standard deviations in flap thicknesses ranged from 4
      to 18.4 MUm. Visual acuities and complications reported with LASIK flaps created
      using femtosecond lasers are within Food and Drug Administration safety and
      efficacy limits. Of all complications, diffuse lamellar keratitis is the most
      common after surgery but is generally mild and self-limited. Corneal sensation
      was reported to normalize by 1 year after surgery. Unique complications of
      femtosecond lasers included transient light-sensitivity syndrome, rainbow glare,
      opaque bubble layer, epithelial breakthrough of gas bubbles, and gas bubbles
      within the anterior chamber. CONCLUSIONS: Available evidence (levels I and II)
      indicates that femtosecond lasers are efficacious devices for creating LASIK
      flaps, with accompanying good visual results. Overall, femtosecond lasers were
      found to be as good as or better than mechanical microkeratomes for creating
      LASIK flaps. There are unique complications that can occur with femtosecond
      lasers, and long-term follow-up is needed to evaluate the technology fully.

PMID- 23174397
TI  - Risk of cardiovascular diseases is increased even with mild diabetic retinopathy:
      the Japan Diabetes Complications Study.
AB  - OBJECTIVE: Diabetic retinopathy (DR) is linked to cardiovascular risk in diabetic
      patients. This study examined whether mild-stage DR is associated with risk of
      coronary heart disease (CHD) and stroke in type 2 diabetic patients of the Japan
      Diabetes Complications Study (JDCS). DESIGN: Prospective cohort study.
      PARTICIPANTS: In the JDCS, there were 2033 Japanese persons with type 2 diabetes
      free of cardiovascular diseases at baseline. METHODS: Diabetic retinopathy was
      ascertained from clinical and photographic grading (70%) following the
      international clinical diabetic retinopathy and diabetic macular edema disease
      severity scales. Incident CHD and stroke were followed up prospectively annually
      up to 8 years. MAIN OUTCOME MEASURES: Eight-year incidence of CHD and stroke
      compared between persons with or without DR. RESULTS: After adjusting for
      traditional cardiovascular risk factors, persons with mild to moderate
      nonproliferative DR had a higher risk of CHD (hazard ratio [HR], 1.69; 95%
      confidence interval [CI], 1.17-2.97) and stroke (HR, 2.69; 95% CI, 1.03-4.86).
      Presence of retinal hemorrhages or microaneurysms was associated with risk of CHD
      (HR, 1.63; 95% CI, 1.04-2.56) but was not associated with stroke (P = 0.06).
      Presence of cotton-wool spots was associated with risk of incident stroke (HR,
      2.39; 95% CI, 1.35-4.24) but was not associated with CHD (P = 0.66). When
      information about DR was added in the prediction models for CHD and stroke based
      on traditional cardiovascular risk factors, the area under the receiver operating
      curve improved from 0.682 to 0.692 and 0.640 to 0.677, and 9% and 13% of persons
      were reclassified correctly for CHD and stroke, respectively. CONCLUSIONS: Type 2
      diabetic patients with even a mild stage of DR, such as dot hemorrhages, are
      already at higher risk of CHD and stroke independent of traditional risk factors.

PMID- 23174399
TI  - Epimacular brachytherapy for neovascular age-related macular degeneration: a
      randomized, controlled trial (CABERNET).
AB  - PURPOSE: To evaluate the safety and efficacy of epimacular brachytherapy (EMBT)
      for the treatment of neovascular age-related macular degeneration (AMD). DESIGN:
      Multicenter, randomized, active-controlled, phase III clinical trial.
      PARTICIPANTS: Four hundred ninety-four participants with treatment-naive
      neovascular AMD. METHODS: Participants with classic, minimally classic, and
      occult lesions were randomized in a 2:1 ratio to EMBT or a ranibizumab
      monotherapy control arm. The EMBT arm received 2 mandated, monthly loading
      injections of 0.5 mg ranibizumab. The control arm received 3 mandated, monthly
      loading injections of ranibizumab then quarterly injections. Both arms also
      received monthly as needed (pro re nata) retreatment. MAIN OUTCOME MEASURES: The
      proportion of participants losing fewer than 15 Early Treatment Diabetic
      Retinopathy Study (ETDRS) letters from baseline visual acuity (VA) and the
      proportion gaining more than 15 ETDRS letters from baseline VA. RESULTS: At 24
      months, 77% of the EMBT group and 90% of the control group lost fewer than 15
      letters. This difference did not meet the prespecified 10% noninferiority margin.
      This end point was noninferior using a 20% margin and a 95% confidence interval
      for the group as a whole and for classic and minimally classic lesions, but not
      for occult lesions. The EMBT did not meet the superiority end point for the
      proportion of participants gaining more than 15 letters (16% for the EMBT group
      vs. 26% for the control group): this difference was statistically significant
      (favoring controls) for occult lesions, but not for predominantly classic and
      minimally classic lesions. Mean VA change was -2.5 letters in the EMBT arm and
      +4.4 letters in the control arm. Participants in the EMBT arm received a mean of
      6.2 ranibizumab injections versus 10.4 in the control arm. At least 1 serious
      adverse event occurred in 54% of the EMBT arm, most commonly postvitrectomy
      cataract, versus 18% in the control arm. Mild, nonproliferative radiation
      retinopathy occurred in 3% of the EMBT participants, but no case was vision
      threatening. CONCLUSIONS: The 2-year efficacy data do not support the routine use
      of EMBT for treatment-naive wet AMD, despite an acceptable safety profile.
      Further safety review is required.

PMID- 23174398
TI  - Associations of anisometropia with unilateral amblyopia, interocular acuity
      difference, and stereoacuity in preschoolers.
AB  - PURPOSE: To evaluate the relationship of anisometropia with unilateral amblyopia,
      interocular acuity difference (IAD), and stereoacuity among Head Start
      preschoolers using both clinical notation and vector notation analyses. DESIGN:
      Multicenter, cross-sectional study. PARTICIPANTS: Three- to 5-year-old
      participants in the Vision in Preschoolers (VIP) study (n = 4040). METHODS:
      Secondary analysis of VIP data from participants who underwent comprehensive eye
      examinations, including monocular visual acuity testing, stereoacuity testing,
      and cycloplegic refraction. Visual acuity was retested with full cycloplegic
      correction when retest criteria were met. Unilateral amblyopia was defined as IAD
      of 2 lines or more in logarithm of the minimum angle of resolution (logMAR)
      units. Anisometropia was defined as a 0.25-diopter (D) or more difference in
      spherical equivalent (SE) or in cylinder power and 2 approaches using power
      vector notation. The percentage with unilateral amblyopia, mean IAD, and mean
      stereoacuity were compared between anisometropic and isometropic children. MAIN
      OUTCOMES MEASURES: The percentage with unilateral amblyopia, mean IAD, and mean
      stereoacuity. RESULTS: Compared with isometropic children, anisometropic children
      had a higher percentage of unilateral amblyopia (8% vs. 2%), larger mean IAD
      (0.07 vs. 0.05 logMAR), and worse mean stereoacuity (145 vs. 117 arc sec; all
      P<0.0001). Larger amounts of anisometropia were associated with higher
      percentages of unilateral amblyopia, larger IAD, and worse stereoacuity (P<0.001
      for trend). The percentage of unilateral amblyopia increased significantly with
      SE anisometropia of more than 0.5 D, cylindrical anisometropia of more than 0.25
      D, vertical and horizontal meridian (J0) or oblique meridian (J45) of more than
      0.125 D, or vector dioptric distance of more than 0.35 D (all P<0.001). Vector
      dioptric distance had greater ability to detect unilateral amblyopia than
      cylinder, SE, J0, or J45 (P<0.001). CONCLUSIONS: The presence and amount of
      anisometropia were associated with the presence of unilateral amblyopia, larger
      IAD, and worse stereoacuity. The threshold level of anisometropia at which
      unilateral amblyopia became significant was lower than current guidelines. Vector
      dioptric distance is more accurate than spherical equivalent anisometropia or
      cylindrical anisometropia in identifying preschoolers with unilateral amblyopia.

PMID- 23174400
TI  - A test revealing the slow acquisition and the dorsal stream substrate of visuo
      spatial perception.
AB  - We propose a battery of simple clinical tests to assess the development of
      elementary visuo-spatial perception. We postulate that most of the tasks we
      selected rely on the visual dorsal stream, although the dual-stream theory
      (Milner & Goodale, 1995) discards the role of the dorsal stream for visual
      perception. In order to test the contribution of this anatomical substrate in
      visuo-spatial perception, we evaluated the performance of two adult patients with
      acquired bilateral occipito-parietal (dorsal stream) damage. Additionally, the
      developmental evolution was assessed by testing 96 children from 4 to 12 years
      old (4 two-year age groups of 24 children). In order to determine the point at
      which children achieved adult performance, and to provide a control group for the
      two patients, we also tested a group of 14 healthy adults. The results
      highlighted the necessity for age-dependent normative values: adult performance
      was achieved only at the age of 8 for length and size comparisons and at 12 for
      dot localisation. In contrast, the ability to judge angles and midlines did not
      reach adult performance even in the oldest group of children, suggesting further
      acquisition through adolescence. Occipito-parietal lesions strongly and
      differentially affected elementary visuo-spatial tasks. In overall scores, the
      two adult patients were approximately at the level of 6-year olds, below the
      outlier limit of the adult group. They were on average within the adult
      interquartile range for processing length and size but clearly outside for the 4
      other subtests (Angle, Midline, Position perception and Position selection). As a
      whole, these data both shed light on the neuroanatomical bases of visuo-spatial
      perception and allow for age-specific comparisons in children with developmental
      disorders potentially linked to visuo-spatial and/or attentional defects.

PMID- 23174401
TI  - Empathy and emotion recognition in people with autism, first-degree relatives,
      and controls.
AB  - Empathy is the lens through which we view others' emotion expressions, and
      respond to them. In this study, empathy and facial emotion recognition were
      investigated in adults with autism spectrum conditions (ASC; N=314), parents of a
      child with ASC (N=297) and IQ-matched controls (N=184). Participants completed a
      self-report measure of empathy (the Empathy Quotient [EQ]) and a modified version
      of the Karolinska Directed Emotional Faces Task (KDEF) using an online test
      interface. Results showed that mean scores on the EQ were significantly lower in
      fathers (p<0.05) but not mothers (p>0.05) of children with ASC compared to
      controls, whilst both males and females with ASC obtained significantly lower EQ
      scores (p<0.001) than controls. On the KDEF, statistical analyses revealed poorer
      overall performance by adults with ASC (p<0.001) compared to the control group.
      When the 6 distinct basic emotions were analysed separately, the ASC group showed
      impaired performance across five out of six expressions (happy, sad, angry,
      afraid and disgusted). Parents of a child with ASC were not significantly worse
      than controls at recognising any of the basic emotions, after controlling for age
      and non-verbal IQ (all p>0.05). Finally, results indicated significant
      differences between males and females with ASC for emotion recognition
      performance (p<0.05) but not for self-reported empathy (p>0.05). These findings
      suggest that self-reported empathy deficits in fathers of autistic probands are
      part of the 'broader autism phenotype'. This study also reports new findings of
      sex differences amongst people with ASC in emotion recognition, as well as
      replicating previous work demonstrating empathy difficulties in adults with ASC.
      The use of empathy measures as quantitative endophenotypes for ASC is discussed.

PMID- 23174402
TI  - Detecting the onset of accelerated long-term forgetting: evidence from temporal
      lobe epilepsy.
AB  - Accelerated long-term forgetting (ALF) refers to a slowly developing anterograde
      amnesia in which material is retained normally over short delays but then
      forgotten at an abnormally fast rate over days to weeks. Such long-term memory
      impairment is not detected by standard clinical tests. This study analysed ALF in
      a temporal lobe epileptic, RY. Key issues addressed were: (i) the timeframe of
      ALF onset; (ii) whether disruption of memory consolidation during sleep is a
      necessary requirement for precipitating ALF; (iii) the effectiveness of repeated
      recall in limiting the impact of ALF. RY's memory for novel word-pairings was
      compared with that of matched controls using cued-recall and forced choice
      recognition (FCR) tests at multiple delays (5, 30, 55, 240 min). To investigate
      the impact of repeated recall some pairings were recalled at all intervals, and
      all material (repeatedly and non-repeatedly recalled) was tested again after a
      24h delay. RY's initial learning and performance at 30 min were normal, but by 55
      min both his cued-recall performance and the subjective quality of his
      recognition memory were significantly impaired. This suggests disruption of
      secondary consolidation processes occurring relatively soon after learning. It
      also raises the possibility of developing a standard test to diagnose ALF within
      a single clinical session rather than requiring multiple visits. Since RY
      remained awake it appears that disruption of memory consolidation during sleep is
      not a necessary condition for him to experience ALF. Repeated recall at multiple
      time-points within the first 4h sustained normal recall performance to 24h,
      indicating repeated recall could form the basis for a protective strategy.

PMID- 23174404
TI  - Are there sex differences in ERPs related to processing empathy-evoking pictures?
AB  - OBJECTIVE: This study aimed to investigate sex differences in the temporal
      dynamics of experiencing empathy by using electrophysiological measurements.
      METHODS: Twenty-five females and 27 males viewed 414 pictures of the
      International affective picture system varying in emotional valence (positive,
      negative and neutral) and presence of humans (human and scenes). EEG event
      related potentials (ERPs) were obtained and correlations were computed with self
      reported empathy. RESULTS: Compared to males, females showed increased anterior
      N2 and parietal LPP amplitudes to humans contrasted with scenes (independent of
      emotional valence) and to negative contrasted with neutral emotions (independent
      of human presence). Independent of sex the N1 and anterior N2 were specifically
      increased for positive human emotions and the parietal LPP for negative human
      emotions. Across sexes, the N2 and LPP human emotion effects and LPP human
      effects were associated with self-reported affective empathy, but not with
      cognitive empathy. CONCLUSIONS: This study provides electrophysiological evidence
      that women prioritize the processing of socially relevant and negative emotional
      information, but that women did not show enhanced brain potentials to pictures
      with positive or negative emotions in humans.

PMID- 23174403
TI  - Developmental changes in within- and between-network connectivity between late
      childhood and adulthood.
AB  - A number of behavioral changes occur between late childhood and adulthood,
      including maturation of social cognition, reward receptivity, impulsiveness, risk
      taking and cognitive control. Although some of these abilities show linear
      improvements with age, some abilities may temporarily worsen, reflecting both the
      restructuring and/or strengthening of connections within some brain systems. The
      current study uses resting state functional connectivity to examine developmental
      differences between late childhood and adulthood in task positive (TP) regions,
      which play a role in cognitive control functions, and task negative (TN) regions,
      which play a role in social cognition, self-referential, and internally-directed
      thought. Within the TP network, developmental differences in connectivity were
      found with the left dorsolateral prefrontal cortex. Within the TN network,
      developmental differences in connectivity were found with a broad area of the
      medial prefrontal cortex and the right parahippocampal gyrus. Connections between
      the two networks also showed significant developmental differences. Stronger
      anticorrelations were found in the TN maps of the adult group for the right
      anterior insula/inferior frontal gyrus, bilateral anterior inferior parietal
      lobule, bilateral superior parietal lobule and an anterior portion of the right
      posterior cingulate cortex. There was a significant brain-behavior relationship
      between the strength of anticorrelation in these regions and inhibitory control
      performance on two Go/No-go tasks suggesting that the development of
      anticorrelations between late childhood and adulthood supports mature inhibitory
      control. Overall, maturation of these networks occurred in specific regions which
      are associated with cognitive control of goal-directed behavior, including those
      involved in working memory, social cognition, and inhibitory control.

PMID- 23174406
TI  - MTHFR 677T variant contributes to diabetic nephropathy risk in Caucasian
      individuals with type 2 diabetes: a meta-analysis.
AB  - OBJECTIVE: Previous studies regarding the association between 5,10
      methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and diabetic
      nephropathy (DN) risk in Caucasian individuals with type 2 diabetes reported
      conflicting results. To derive a more precise estimation of this association, a
      meta-analysis was performed. MATERIALS/METHODS: Odds ratios (ORs) with
      corresponding 95% confidence intervals (95% CIs) were pooled to assess the
      association between MTHFR C677T polymorphism and DN risk. Finally, 10 case
      control studies with a total of 1590 DN cases and 1555 type 2 diabetic controls
      without DN were included. RESULTS: Overall, there was an association between
      MTHFR C677T polymorphism and increased risk of DN under four comparison models
      (OR T vs. C=1.50, 95% CI 1.07-2.02, P=0.02; OR TT vs. CC=2.09, 95% CI 1.07-4.08,
      P=0.03; OR TT vs. TC+CC=1.70, 95% CI 1.10-2.63, P=0.017; OR TC+TT vs. CC=1.85,
      95% CI 1.19-2.88, P=0.006). Sensitivity analysis suggested exclusion of any
      single study did not materially alter the overall pooled ORs above. CONCLUSIONS:
      This meta-analysis supports that there is an association between MTHFR C677T
      polymorphism and DN risk, and MTHFR 677T variant contributes to increased risk of
      DN in Caucasian individuals with type 2 diabetes.

PMID- 23174405
TI  - Acute effects of different diet compositions on skeletal muscle insulin
      signalling in obese individuals during caloric restriction.
AB  - OBJECTIVE: The cellular effects of restricting fat versus carbohydrate during a
      low-calorie diet are unclear. The aim of this study was to examine acute effects
      of energy and macronutrient restriction on skeletal muscle insulin signalling in
      obesity. MATERIALS/METHODS: Eighteen obese individuals without diabetes underwent
      euglycemic-hyperinsulinemic clamp and skeletal muscle biopsy after: (a) 5days of
      eucaloric diet (30% fat, 50% carbohydrate), and (b) 5days of a 30% calorie
      restricted diet, either low fat/high carbohydrate (LF/HC: 20% fat, 60%
      carbohydrate) or high-fat/low carbohydrate (HF/LC: 50% fat, 30% carbohydrate).
      RESULTS: Weight, body composition, and insulin sensitivity were similar between
      groups after eucaloric diet. Weight loss was similar between groups after
      hypocaloric diet, 1.3+/-1.3kg (p<0.0001 compared with eucaloric). Whole-body
      insulin sensitivity was unchanged after calorie restriction and similar between
      groups. However, ex vivo skeletal muscle insulin signalling differed depending on
      macronutrient composition of calorie-restricted diet. Skeletal muscle of the
      LF/HC group had increased insulin-stimulated tyrosine phosphorylation of IRS-1,
      decreased insulin-stimulated Ser307 phosphorylation of IRS-1, and increased IRS-1
      associated phosphatidylinositol (PI)3-kinase activity. Conversely, insulin
      stimulation of tyrosine phosphorylated IRS-1 was absent and serine 307
      phosphorylation of IRS-1 was increased on HF/LC, with blunting of IRS-1
      associated PI3-kinase activity. CONCLUSION: Acute caloric restriction with an
      LF/HC diet alters skeletal muscle insulin signalling in a way that improves
      insulin sensitivity, while acute caloric restriction with an HF/LC diet induces
      changes compatible with insulin resistance. In both cases, ex vivo changes in
      skeletal muscle insulin signalling appear prior to changes in whole body insulin
      sensitivity.

PMID- 23174407
TI  - High serum C1q-adiponectin/total adiponectin ratio correlates with coronary
      artery disease in Japanese type 2 diabetics.
AB  - OBJECTIVE: Adiponectin, an adipocyte-derived protein, has potential
      antiatherogenic properties. Low levels of serum total-adiponectin (Total-APN)
      correlate with diabetes and coronary artery disease (CAD). Adiponectin and C1q
      form a protein complex in blood, and serum C1q-binding adiponectin (C1q-APN) can
      be measured. We investigated the correlation between C1q-APN and CAD in patients
      with type 2 diabetes mellitus (T2DM). METHODS: The study subjects were 107
      outpatients with T2DM who underwent evaluation for CAD. Blood C1q, Total-APN,
      high-molecular weight-adiponectin (HMW-APN) and C1q-APN were measured by enzyme
      linked immunosorbent assays. RESULTS: Serum levels of C1q-APN/Total-APN ratio
      were higher in patients diagnosed with CAD (10.47+/-0.59, mean+/-SEM, n=54) than
      those without CAD (8.88+/-0.60, n=53, p=0.0482). Age- and sex-adjusted logistic
      regression analysis identified serum C1q-APN/Total-APN ratio and hypertension as
      significant and independent determinants of CAD. A high serum C1q-APN/Total-APN
      ratio was associated with 3.965-fold increase in CAD prevalence. CONCLUSIONS:
      High serum C1q-APN/Total-APN ratio correlates with CAD in T2DM.

PMID- 23174408
TI  - Fabrication and evaluation of pH-modulated solid dispersion for telmisartan by
      spray-drying technique.
AB  - The present study was undertaken to overcome the problems associated with
      solubility, dissolution and oral bioavailability of a poorly water-soluble
      ionizable drug, telmisartan (TMS). For these purposes, a solubility test was
      carried to select the appropriate formulation composition from various carriers
      and alkalizers. Solid dispersions (SDs) of TMS were prepared at different drug-to
      carrier ratios by the spray-drying technique, and were characterized by
      dissolution and aqueous solubility studies. The optimum formulation was
      investigated by dissolution studies at different pH and water media and its solid
      state characterisations were performed by scanning electron microscopy (SEM),
      differential scanning calorimetry (DSC) and X-ray diffraction (XRD) studies. In
      solubility and dissolution tests, all TMS-loaded pH-modulated SDs (pH(M)-SDs)
      exhibited marked improvement in the dissolution behavior when compared with
      crystalline TMS powder. The optimum formulation of pH(M)-SD consisted of TMS/PVP
      (polyvinylpyrrolidone) K30/Na(2)CO(3) at a weight ratio of 2/0.5/3 and showed
      significant improvement in the aqueous solubility and dissolution rate by
      approximately 40,000- and 3-fold, respectively, compared to TMS powder. Solid
      state characterization revealed the changed in crystallinity of TMS into
      amorphous state. Furthermore, area under the drug concentration time-curve (AUC)
      of TMS from the pH(M)-SD increased by 13.4- and 2.1-fold, compared with TMS
      powder and commercial product, respectively. According to these observations,
      taken together with dissolution and pharmacokinetic behaviors, pH-modulated SD in
      the presence of an alkalizer for a poorly water-soluble ionizable drug, TMS,
      appeared to be efficacious for enhancing its bioavailability.

PMID- 23174410
TI  - Polysaccharide-anchored fatty acid liposome.
AB  - In this study, the preparation of N-pamitoyl chitosan (ChP) anchored oleic acid
      (OA) liposome was demonstrated. Two different types of water-soluble ChPs with
      different degrees of acylation (DA) were selected for this study. The presence of
      ChPs on the surface of OA liposome was confirmed with their micrographs and
      physicochemical properties. The "peeling off" effect on the surface of the ChP
      anchored OA (OAChP) liposomes was observed on the atomic force microscope
      micrographs and confirmed the presence of the ChPs layer on the liposome surface.
      The surface tension of the OAChPs liposome solution was found to be higher than
      that of the OA liposome solution. This result indicated the removal of OA monomer
      by ChPs from the air-water interface. The increase in the minimum area per
      headgroup (A(min)) of the OA with the presence of ChPs has further proved the
      interaction between OA monomer and the hydrophobic moieties of the ChPs. The ChPs
      anchored onto the OA monolayer increased the curvature of the OAChP liposomes
      monolayer and reduced the liposome size. The size of the OAChP liposomes was
      reduced by 30 nm as compared with the unmodified OA liposome. Results revealed
      that the anchored ChPs can improve the integrity and rigidity of the OA liposome.

PMID- 23174409
TI  - Abrogation of the accelerated blood clearance phenomenon by SOXL regimen: promise
      for clinical application.
AB  - We recently proposed an S-1 combined with oxaliplatin (SOXL) regimen, a
      combination treatment consisting of oral metronomic S-1 dosing and intravenous
      administration of oxaliplatin (l-OHP) containing PEGylated liposomes, which
      showed potent antitumor activity in vivo. PEGylated liposomes induce what is
      referred to as the "accelerated blood clearance (ABC) phenomenon" upon repeated
      administration and consequently lose their long-circulating characteristics. This
      phenomenon seems to pose an impediment for the clinical application and use of
      PEGylated liposomal formulations. In the present study, l-OHP-containing
      PEGylated liposomes in the SOXL regimen significantly attenuated the ABC
      phenomenon in a dose-dependent manner through suppression of the anti-PEG IgM
      response, which allowed an enhanced hepatic uptake of subsequently injected test
      PEGylated liposomes. In tumor-bearing mice, the abrogation of the ABC phenomenon
      restored intratumor accumulation of subsequently injected PEGylated liposomes.
      Consequently, the therapeutic efficacy of the SOXL regimen over the combination
      of the free form of the drugs was credited not only with the selective delivery
      of drugs to the tumor tissue but also with ensuring an adequate accumulation of
      subsequent doses within the tumor tissue. The SOXL regimen we proposed may hold
      promise as a safe and effective treatment regimen for advanced colorectal cancer.

PMID- 23174411
TI  - Chitosan oligosaccharide-arachidic acid-based nanoparticles for anti-cancer drug
      delivery.
AB  - Chitosan oligosaccharide-arachidic acid (CSOAA) conjugate was successfully
      synthesized and used for the development of self-assembled nanoparticles for
      doxorubicin (DOX) delivery. The molar substitution of AA on CSO and critical
      micelle concentration (CMC) of CSOAA were measured. Physicochemical properties of
      DOX-loaded CSOAA-based nanoparticles, such as particle size, zeta potential and
      morphology, were also characterized. The DOX-loaded CSOAA-based nanoparticles
      showed spherical shape with a mean diameter of 130 nm and positive charge.
      According to the result of in vitro release test, DOX-loaded CSOAA-based
      nanoparticles exhibited sustained and pH-dependent drug release profiles. The
      CSOAA showed negligible cytotoxicity in FaDu, human head and neck cancer, cells.
      Cellular uptake of DOX in FaDu cells was higher in the nanoparticle-treated group
      compared to the free DOX group. The anti-tumor efficacy of DOX-loaded
      nanoparticles was also verified in FaDu tumor xenografted mouse model. These
      results suggested that synthesized amphiphilic CSOAA might be used for the
      preparation of self-assembled nanoparticles for anti-cancer drug delivery.

PMID- 23174412
TI  - A miniaturized flow-through cell to evaluate skin permeation of endoxifen.
AB  - Endoxifen, an anti-estrogenic agent, has been recently implicated in the use of
      breast cancer. Its physicochemical properties make it a good candidate for
      transdermal delivery. However, as an investigative drug, its limited supply makes
      it difficult to conduct extensive pre-formulation studies. To address this issue,
      a miniaturized flow-through diffusion cell has been fabricated that utilized
      minimal amounts of the drug for in vitro skin permeation studies. The novel flow
      through cells have been validated against horizontal diffusion cells and shown to
      cause no noticeable damage to the applied skin, as observed by histological
      sectioning. The cells were also demonstrated to be useful in search of suitable
      enhancers for endoxifen. Endoxifen permeation using permeation enhancers was
      tested by using this new device and limonene was found to achieve highest flux,
      attaining the requirement for clinical applications. The fabricated cells can
      thus be useful in carrying out pre-formulation studies for expensive, new drug
      entities, both in industrial as well as academic research.

PMID- 23174413
TI  - Real-time monitoring of lubrication properties of magnesium stearate using NIR
      spectrometer and thermal effusivity sensor.
AB  - Real-time monitoring techniques based on an NIR spectrometer and a thermal
      effusivity sensor for lubrication properties of magnesium stearate (Mg-St) are
      proposed. The lubrication properties of Mg-St are defined by its concentration
      distribution and flatting state in a mixture. The concentration distribution of
      Mg-St significantly affects the absorbance in the NIR wavelength region between
      1128 nm and 1240 nm. Thus, the absorbance area in this region after baseline
      correction was selected as a monitoring index (MI). In laboratory-scale
      experiments, the difference of Mg-St concentration distribution could be detected
      by the proposed MI with high sensitivity. In addition, experimental results using
      spherical mannitol granules confirmed that the changes of the flatting state of
      Mg-St could also be detected by the proposed MI. Similar experiments with
      spherical mannitol granules and the thermal effusivity sensor confirmed that
      effusivity could also be used to detect the changes of the flatting state of Mg
      St. The applicability of these monitoring techniques was verified using a 2000 L
      commercial-scale blender equipped with the NIR spectrometer and the thermal
      effusivity sensor. The results showed that both lubrication properties could be
      monitored by the proposed MI, and that the flatting state of Mg-St could be
      monitored more sensitively by using the effusivity.

PMID- 23174414
TI  - Guided preparedness planning with lay communities: enhancing capacity of rural
      emergency response through a systems-based partnership.
AB  - INTRODUCTION: Community disaster preparedness plans, particularly those with
      content that would mitigate the effects of psychological trauma on vulnerable
      rural populations, are often nonexistent or underdeveloped. The purpose of the
      study was to develop and evaluate a model of disaster mental health preparedness
      planning involving a partnership among three, key stakeholders in the public
      health system. METHODS: A one-group, post-test, quasi-experimental design was
      used to assess outcomes as a function of an intervention designated Guided
      Preparedness Planning (GPP). The setting was the eastern-, northern-, and mid
      shore region of the state of Maryland. Partner participants were four local
      health departments (LHDs), 100 faith-based organizations (FBOs), and one academic
      health center (AHC)-the latter, collaborating entities of the Johns Hopkins
      University and the Johns Hopkins Health System. Individual participants were 178
      community residents recruited from counties of the above-referenced geographic
      area. Effectiveness of GPP was based on post-intervention assessments of trainee
      knowledge, skills, and attitudes supportive of community disaster mental health
      planning. Inferences about the practicability (feasibility) of the model were
      drawn from pre-defined criteria for partner readiness, willingness, and ability
      to participate in the project. Additional aims of the study were to determine if
      LHD leaders would be willing and able to generate post-project strategies to
      perpetuate project-initiated government/faith planning alliances
      (sustainability), and to develop portable methods and materials to enhance model
      application and impact in other health jurisdictions (scalability). RESULTS: The
      majority (95%) of the 178 lay citizens receiving the GPP intervention and
      submitting complete evaluations reported that planning-supportive objectives had
      been achieved. Moreover, all criteria for inferring model feasibility,
      sustainability, and scalability were met. CONCLUSIONS: Within the span of a six
      month period, LHDs, FBOs, and AHCs can work effectively to plan, implement, and
      evaluate what appears to be an effective, practical, and durable model of
      capacity building for public mental health emergency planning.

PMID- 23174415
TI  - Effects of bisphenol A on the microtubule arrays in root meristematic cells of
      Pisum sativum L.
AB  - Bisphenol A (BPA), a widely used chemical in the plastics industry that displays
      weak oestrogenic properties, is an emerging environmental pollutant, potentially
      harmful to living organisms. The presumed cytotoxicity of BPA to plant cells has
      been poorly studied. To understand how BPA might influence plant cell division
      and affect the underlying cytoskeleton, the effects of BPA on the microtubule
      (MT) arrays of meristematic root-tip cells of Pisum sativum L. were investigated.
      Root tips of young seedlings were exposed to 20, 50 and 100mg/L BPA for 1, 3, 6,
      12 and 24h. The effects of each treatment were determined by means of confocal
      laser scanning microscopy after immunolabelling of tubulin and counterstaining of
      DNA, and by use of light and transmission electron microscopy. It was found that
      BPA affected normal chromosome segregation, hampered the completion of
      cytokinesis and deranged interphase and mitotic MT arrays. BPA effects were
      dependent on the stage of each cell at the time of BPA entrance. Moreover, BPA
      induced the formation of macrotubules with a mean diameter of 32 +/- 0.14 nm,
      compared with 23 +/- 0.70 nm for the MT arrays in untreated cells. Finally, all
      MT arrays and macrotubules were depolymerised upon longer treatment. Taken
      together, the data suggest that BPA exerts acute anti-mitotic effects on
      meristematic root-tip cells of P. sativum, MT arrays constitute a primary sub
      cellular target of BPA toxicity, and the manifested chromosomal abnormalities
      could be attributed to the disruption of the MT cytoskeleton.

PMID- 23174416
TI  - Attention modulates the use of spectral attributes in vowel discrimination:
      behavioral and event-related potential evidence.
AB  - Speech contains a variety of acoustic cues to auditory and phonetic contrasts
      that are exploited by the listener in decoding the acoustic signal. In three
      experiments, we tried to elucidate whether listeners rely on formant peak
      frequencies or whole spectrum attributes in vowel discrimination. We created two
      vowel continua in which the acoustic distance in formant frequencies was constant
      but the continua differed in spectral moments (i.e., the whole spectrum modeled
      as a probability density function). In Experiment 1, we measured reaction times
      and response accuracy while listeners performed a go/no-go discrimination task.
      The results indicated that the performance of the listeners was based on the
      spectral moments (especially the first and second moments), and not on formant
      peaks. Behavioral results in Experiment 2 showed that, when the stimuli were
      presented in noise eliminating differences in spectral moments between the two
      continua, listeners employed formant peak frequencies. In Experiment 3, using the
      same listeners and stimuli as in Experiment 1, we measured an automatic brain
      potential, the mismatch negativity (MMN), when listeners did not attend to the
      auditory stimuli. Results showed that the MMN reflects sensitivity only to the
      formant structure of the vowels. We suggest that the auditory cortex
      automatically and pre-attentively encodes formant peak frequencies, whereas
      attention can be deployed for processing additional spectral information, such as
      spectral moments, to enhance vowel discrimination.

PMID- 23174417
TI  - Diphenyleneiodonium protects preoligodendrocytes against endotoxin-activated
      microglial NADPH oxidase-generated peroxynitrite in a neonatal rat model of
      periventricular leukomalacia.
AB  - The contribution of microglial activation to preoligodendroglial (preOL) damage
      in the central nervous system (CNS) is considered to be one of the principal
      causes of periventricular leukomalacia (PVL) pathogenesis. The present study
      explores the effect of diphenyleneiodonium (DPI), a NADPH oxidase (NOX)
      inhibitor, on protection of preOLs from bacterial lipopolysaccharide (LPS)
      induced microglial toxicity in vivo and in vitro. In vitro, preOLs co-cultured
      with microglia exhibited increased preOL apoptosis, accompanied by overproduction
      of superoxide anion (O(2)(-)) and the formation of peroxynitrite (ONOO(-)) after
      LPS exposure. LPS also significantly up-regulated accumulation of activated
      microglial NOX subunits p67-phox and gp91-phox in the plasma membrane.
      Diphenyleneiodonium (DPI) (10MUm) was found to significantly attenuate up
      regulation of this NOX activity. In vivo, DPI was administered (1mg/kg/day) by
      subcutaneous injection for 3 days to two-day-old neonatal Sprague-Dawley rats
      subjected to intracerebral injection of LPS. Treatment with DPI within 24h of LPS
      injection significantly ameliorated white matter injury, decreasing preOL loss,
      O(2)(-) generation, and ONOO(-) formation, and inhibiting p67-phox, gp91-phox
      synthesis and p67phox membrane translocation in microglia. These results
      indicated that LPS-induced preOL apoptosis may have been mediated by microglia
      derived ONOO(-). DPI prevented this LPS-induced brain injury, most likely by
      inhibiting ONOO(-) formation via NOX, thereby preventing preOL loss and immature
      white matter injury.

PMID- 23174419
TI  - Predictive modeling of the virtual Hemi-Fontan operation for second stage single
      ventricle palliation: two patient-specific cases.
AB  - Single ventricle hearts are congenital cardiovascular defects in which the heart
      has only one functional pumping chamber. The treatment for these conditions
      typically requires a three-staged operative process where Stage 1 is typically
      achieved by a shunt between the systemic and pulmonary arteries, and Stage 2 by
      connecting the superior venous return to the pulmonary circulation. Surgically,
      the Stage 2 circulation can be achieved through a procedure called the Hemi
      Fontan, which reconstructs the right atrium and pulmonary artery to allow for an
      enlarged confluence with the superior vena cava. Based on pre-operative data
      obtained from two patients prior to Stage 2 surgery, we developed two patient
      specific multi-scale computational models, each including the 3D geometrical
      model of the surgical junction constructed from magnetic resonance imaging, and a
      closed-loop systemic lumped-parameter network derived from clinical measurements.
      "Virtual" Hemi-Fontan surgery was performed on the 3D model with guidance from
      clinical surgeons, and a corresponding multi-scale simulation predicts the
      patient's post-operative hemodynamic and physiologic conditions. For each
      patient, a post-operative active scenario with an increase in the heart rate (HR)
      and a decrease in the pulmonary and systemic vascular resistance (PVR and SVR)
      was also performed. Results between the baseline and this "active" state were
      compared to evaluate the hemodynamic and physiologic implications of changing
      conditions. Simulation results revealed a characteristic swirling vortex in the
      Hemi-Fontan in both patients, with flow hugging the wall along the SVC to Hemi
      Fontan confluence. One patient model had higher levels of swirling,
      recirculation, and flow stagnation. However, in both models, the power loss
      within the surgical junction was less than 13% of the total power loss in the
      pulmonary circulation, and less than 2% of the total ventricular power. This
      implies little impact of the surgical junction geometry on the SVC pressure,
      cardiac output, and other systemic parameters. In contrast, varying HR, PVR, and
      SVR led to significant changes in theses clinically relevant global parameters.
      Adopting a work-flow of customized virtual planning of the Hemi-Fontan procedure
      with patient-specific data, this study demonstrates the ability of multi-scale
      modeling to reproduce patient specific flow conditions under differing
      physiological states. Results demonstrate that the same operation performed in
      two different patients can lead to different hemodynamic characteristics, and
      that modeling can be used to uncover physiologic changes associated with
      different clinical conditions.

PMID- 23174418
TI  - Advances in assessment of bone porosity, permeability and interstitial fluid
      flow.
AB  - This contribution reviews recent research performed to assess the porosity and
      permeability of bone tissue with the objective of understanding interstitial
      fluid movement. Bone tissue mechanotransduction is considered to occur due to the
      passage of interstitial pore fluid adjacent to dendritic cell structures in the
      lacunar-canalicular porosity. The movement of interstitial fluid is also
      necessary for the nutrition of osteocytes. This review will focus on four topics
      related to improved assessment of bone interstitial fluid flow. First, the
      advantages and limitations of imaging technologies to visualize bone porosities
      and architecture at several length scales are summarized. Second, recent efforts
      to measure the vascular porosity and lacunar-canalicular microarchitecture are
      discussed. Third, studies associated with the measurement and estimation of the
      fluid pressure and permeability in the vascular and lacunar-canalicular domains
      are summarized. Fourth, the development of recent models to represent the
      interchange of fluids between the bone porosities is described.

PMID- 23174420
TI  - Comparison of partial least squares regression and principal component regression
      for pelvic shape prediction.
AB  - This paper studied two different regression techniques for pelvic shape
      prediction, i.e., the partial least square regression (PLSR) and the principal
      component regression (PCR). Three different predictors such as surface landmarks,
      morphological parameters, or surface models of neighboring structures were used
      in a cross-validation study to predict the pelvic shape. Results obtained from
      applying these two different regression techniques were compared to the
      population mean model. In almost all the prediction experiments, both regression
      techniques unanimously generated better results than the population mean model,
      while the difference on prediction accuracy between these two regression methods
      is not statistically significant (alpha=0.01).

PMID- 23174423
TI  - Peer consultation on relationship between PAC profile and toxicity of petroleum
      substances.
AB  - An expert peer consultation panel reviewed a report by the PAC Analysis Task
      Group, which hypothesized that systemic, developmental, and reproductive toxicity
      observed in repeated-dose dermal toxicity studies was related to polycyclic
      aromatic compound (PAC) content. Peer consultations seek to solicit scientific
      and technical input from experts on the scientific basis and merits of the
      subject report. This peer consultation panel included nine scientists with
      expertise in petroleum chemistry, biostatistics, toxicology, risk assessment,
      structure activity, and reproductive and developmental toxicology. The panel
      evaluated the technical quality of the PAC report and provided recommendations
      for improving the statistical and biological approaches. The PAC report authors
      revised their methods and documentation, which are published elsewhere in this
      supplement. A review of the post peer consultation manuscripts confirmed that
      many of the key suggestions from expert panel members were considered and
      incorporated. In cases where the PAC report authors did not fully incorporate
      panel suggestions from the peer consultation, they have provided an explanation
      and support for their decision. This peer consultation demonstrates the value of
      formal engagement of peers in development of new scientific methods and
      approaches. 

PMID- 23174422
TI  - High-resolution CFD detects high-frequency velocity fluctuations in bifurcation,
      but not sidewall, aneurysms.
AB  - High-frequency flow fluctuations in intracranial aneurysms have previously been
      reported in vitro and in vivo. On the other hand, the vast majority of image
      based computational fluid dynamics (CFD) studies of cerebral aneurysms report
      periodic, laminar flow. We have previously demonstrated that transitional flow,
      consistent with in vivo reports, can occur in a middle cerebral artery (MCA)
      bifurcation aneurysm when ultra-high-resolution direct numerical simulation
      methods are applied. The object of the present study was to investigate if such
      high-frequency flow fluctuations might be more widespread in adequately-resolved
      CFD models. A sample of N=12 anatomically realistic MCA aneurysms (five
      unruptured, seven ruptured), was digitally segmented from CT angiograms. Four
      were classified as sidewall aneurysms, the other eight as bifurcation aneurysms.
      Transient CFD simulations were carried out assuming a steady inflow velocity of
      0.5m/s, corresponding to typical peak systolic conditions at the MCA. To allow
      for detection of clinically-reported high-frequency flow fluctuations and
      resulting flow structures, temporal and spatial resolutions of the CFD
      simulations were in the order of 0.1 ms and 0.1 mm, respectively. A transient
      flow response to the stationary inflow conditions was found in five of the 12
      aneurysms, with energetic fluctuations up to 100 Hz, and in one case up to 900
      Hz. Incidentally, all five were ruptured bifurcation aneurysms, whereas all four
      sidewall aneurysms, including one ruptured case, quickly reached a stable, steady
      state solution. Energetic, rapid fluctuations may be overlooked in CFD models of
      bifurcation aneurysms unless adequate temporal and spatial resolutions are used.
      Such fluctuations may be relevant to the mechanobiology of aneurysm rupture, and
      to a recently reported dichotomy between predictors of rupture likelihood for
      bifurcation vs. sidewall aneurysms.

PMID- 23174421
TI  - Toward patient-specific simulations of cardiac valves: state-of-the-art and
      future directions.
AB  - Recent computational methods enabling patient-specific simulations of native and
      prosthetic heart valves are reviewed. Emphasis is placed on two critical
      components of such methods: (1) anatomically realistic finite element models for
      simulating the structural dynamics of heart valves; and (2) fluid structure
      interaction methods for simulating the performance of heart valves in a patient
      specific beating left ventricle. It is shown that the significant progress
      achieved in both fronts paves the way toward clinically relevant computational
      models that can simulate the performance of a range of heart valves, native and
      prosthetic, in a patient-specific left heart environment. The significant
      algorithmic and model validation challenges that need to be tackled in the future
      to realize this goal are also discussed.

PMID- 23174424
TI  - Estimates of daily di-isodecyl phthalate (DIDP) intake calculated from urinary
      biomonitoring data.
AB  - Biomonitoring of chemical species in biologic media can be a valuable tool in
      risk assessment since it informs directly on aggregate exposures. While advances
      in the analytical techniques required for biomonitoring have resulted in
      increased sensitivity for the detection of chemical species, the detection of a
      chemical substance in a biological medium (such as blood, urine or breast milk)
      does not mean that the chemical causes or is associated with an adverse health
      outcome. In this paper, intake estimates for di-isodecyl phthalate (DIDP), a high
      molecular weight general purpose plasticizer, were calculated from urinary
      biomonitoring data representing various population segments and geographic
      locales. From these data, intake estimates converge on a mean that is <1
      MUg/kg/day (95th% < 5 MUg/kg/day). This intake estimate is at least two orders of
      magnitude lower than the health-based exposure guidance values (38-150
      MUg/kg/day) which have been proposed by regulatory authorities and other
      authoritative bodies as safe exposure levels.

PMID- 23174425
TI  - Stroke thrombolysis in England: an age stratified analysis of practice and
      outcome.
AB  - INTRODUCTION: until very recently, only small numbers of older patients with
      stroke had been recruited into randomised controlled trials of thrombolysis with
      recombinant tissue plasminogen activator (rt-PA) and patients aged >80 are
      excluded in the European licence for this therapy. We aimed to estimate the use
      and outcome of stroke thrombolysis in England across age groups, including the
      oldest-old. METHODS: data were collected as part of the Stroke Improvement
      National Audit Programme. All adults receiving thrombolysis for acute ischaemic
      stroke as part of routine care between April 2010 and November 2011 were
      included. Multilevel multivariable logistic regression was used to analyse the
      associations between age, process of care and 30-day mortality. RESULTS: of
      37,151 adults admitted with acute ischaemic stroke, 3,374 (9.1%) received rt-PA.
      Patients aged >80 accounted for 21% of the thrombolysis recipients and 4.8% of
      patients in this age group received rt-PA. Treatment times were similar across
      all age groups, but older thrombolysis recipients were more likely to have Total
      anterior circulation infarct strokes and less likely to be functionally
      independent prior to stroke. Similar rates of post-thrombolysis complications
      were observed between patients aged >80 and younger patients. Mortality was high
      among older patients whether they were treated with rt-PA or not. Among patients
      treated with rt-PA, those aged 81-90 and >90 had, respectively, 34 and 270%
      higher odds of 30-day mortality than patients aged 70-80. CONCLUSION: treatment
      with rt-PA is now carried out frequently for older stroke patients in England.
      Their care is as timely as younger patients with no higher risk of major
      complication but mortality rates in older patients with stroke remain high.

PMID- 23174426
TI  - Structured population models: introduction.

PMID- 23174427
TI  - Relational processing following stroke.
AB  - The research examined relational processing following stroke. Stroke patients (14
      with frontal, 30 with non-frontal lesions) and 41 matched controls completed four
      relational processing tasks: sentence comprehension, Latin square matrix
      completion, modified Dimensional Change Card Sorting, and n-back. Each task
      included items at two or three levels of relational complexity. Relational
      processing was impaired in the stroke groups. This was due mainly to items at the
      intermediate ternary-relational level of complexity. Less complex binary
      relational items and more complex quaternary-relational items (the latter are
      difficult for adults generally) were less sensitive to stroke status. Impairment
      was greater in frontal than non-frontal stroke patients. Positive inter
      correlations among measures supported the domain-general nature of relational
      processing. Implications for assessment and intervention are discussed.

PMID- 23174428
TI  - Bilateral saccadic eye movements and tactile stimulation, but not auditory
      stimulation, enhance memory retrieval.
AB  - Recent research has shown superior memory retrieval when participants make a
      series of horizontal saccadic eye movements between the memory encoding phase and
      the retrieval phase compared to participants who do not move their eyes or move
      their eyes vertically. It has been hypothesized that the rapidly alternating
      activation of the two hemispheres that is associated with the series of left
      right eye movements is critical in causing the enhanced retrieval. This
      hypothesis predicts a beneficial effect on retrieval of alternating left-right
      stimulation not only of the visuomotor system, but also of the somatosensory
      system, both of which have a strict contralateral organization. In contrast, this
      hypothesis does not predict an effect, or a weaker effect, on retrieval of
      alternating left-right stimulation of the auditory system, which has a much less
      lateralized organization. Consistent with these predictions, we replicated the
      horizontal saccade-induced retrieval enhancement (Experiment 1) and showed that a
      similar retrieval enhancement occurs after alternating left-right tactile
      stimulation (Experiment 2). Furthermore, retrieval was not enhanced after
      alternating left-right auditory stimulation compared to simultaneous bilateral
      auditory stimulation (Experiment 3). We discuss the possibility that alternating
      bilateral activation of the left and right hemispheres exerts its effects on
      memory by increasing the functional connectivity between the two hemispheres. We
      also discuss the findings in the context of clinical practice, in which bilateral
      eye movements (EMDR) and auditory stimulation are used in the treatment of post
      traumatic stress disorder.

PMID- 23174429
TI  - Neural correlates of stimulus response and stimulus outcome shifting in healthy
      participants and MS patients.
AB  - INTRODUCTION: Adaptation to changing situations can be mediated by two
      strategies: (1) Evaluation of a response and (2) Evaluation of outcome values in
      relation to objects. Previous studies indicate that response shifting is
      associated with a network comprising the left frontal cortex and parietal cortex
      connected by the superior longitudinal fascicle, whereas outcome evaluation is
      associated with a network consisting of the orbitofrontal cortex, amygdala and
      uncinate fascicle. However, these studies rarely compared both kinds of
      adaptation directly and existing fMRI studies with healthy subjects are not
      informative about the role of the two fiber systems. METHODS: We analyzed
      stimulus response shifting and stimulus outcome shifting in two studies, one fMRI
      study on healthy participants and one study on patients with MS involving
      structural MRI (Diffusion Tensor Imaging, Voxel Based Morphometry, Ventricular
      volumetry). Two tasks were used, identical in presentation but different in
      instruction, controlling for effects of lower level processing. In the SRS task,
      participants had to perform a "Go" or "NoGo" response depending on a stimulus
      change: if the stimulus remained the same, they had to continue with the former
      type of response, if it changed they had to adapt their response pattern. In the
      SOS task they had to perform a "Go" response only if the presented stimulus
      corresponded to that of an internal alternating series. RESULTS: fMRI findings
      showed that SRS is related to a bilateral parietal-premotor network. In the left
      hemisphere the prefrontal cortex was also involved. SOS was lateralized to the
      right hemisphere, particularly to the anterior temporal pole and amygdala, and
      the inferior parietal cortex. MS patients impaired on this task suffered from
      lesions in the right uncinate fascicle and showed an enlarged right frontal
      lateral ventricle. CONCLUSION: With physically identical tasks, a functional
      neuronal segregation can be demonstrated for stimulus response shifting
      (bilateral activations with a focus in the left prefrontal cortex) and stimulus
      outcome shifting (right anterior temporal lobe and right supramarginal gyrus).

PMID- 23174430
TI  - fMRI evidence for dorsal stream processing abnormality in adults born preterm.
AB  - We investigated the consequences of premature birth on the functional
      neuroanatomy of the dorsal stream of visual processing. fMRI was recorded while
      sixteen healthy participants, 8 (two men) adults (19 years 6 months old, SD 10
      months) born premature (mean gestational age 30 weeks), referred to as Premas,
      and 8 (two men) matched controls (20 years 1 month old, SD 13 months), performed
      a 1-back memory task of Object or Grip information using a hand grasping a
      drinking vessel as stimulus. While history of prematurity did not significantly
      affect task performance, Group by Task analysis of variance in regions of
      interest spanning the occipital, temporal and parietal lobes revealed main
      effects of Task and interactions between the two factors. Object processing
      activated the left inferior occipital cortex and bilateral ventral temporal
      regions, belonging to the ventral stream, with no effect of Group. Grip
      processing across groups activated the early visual cortex and the left
      supramarginal gyrus belonging to the dorsal stream. Group effect on the brain
      activity during Grip suggested that Controls represented the actions' goal while
      Premas relied more on low-level visual information. This shift from higher- to
      lower-order visual processing between Controls and Premas may reflect a more
      general trend, in which Premas inadequately recruit higher-order visual functions
      for dorsal stream task performance, and rely more on lower-level functions.

PMID- 23174431
TI  - Impact of intention on the ERP correlates of face recognition.
AB  - The present study investigated the impact of study-test similarity on face
      recognition by manipulating, in the same experiment, the expression change (same
      vs. different) and the task-processing context (inclusion vs. exclusion
      instructions) as within-subject variables. Consistent with the dual-process
      framework, the present results showed that participants performed better on the
      inclusion task than on the exclusion task, with no response bias. A mid-frontal
      FN400 old/new effect and a parietal old/new effect were found in both tasks.
      However, modulations of the ERP old/new effects generated by the expression
      change on recognized faces differed across tasks. The modulations of the ERP
      old/new effects were proportional to the degree of matching between the study
      face and the recognition face in the inclusion task, but not in the exclusion
      task. The observed modulation of the FN400 old/new effect by the task
      instructions when familiarity and conceptual priming were kept constant indicates
      that these early ERP correlates of recognition depend on voluntary task-related
      control. The present results question the idea that FN400 reflects implicit
      memory processes such as conceptual priming and show that the extent to which the
      FN400 discriminates between conditions depends on the retrieval orientation at
      test. They are discussed in relation to recent controversies about the ERP
      correlates of familiarity in face recognition. This study suggests that while
      both conceptual and perceptual information can contribute to the familiarity
      signal reflected by the FN400 effect, their relative contributions vary with the
      task demands.

PMID- 23174432
TI  - Reliability and plasticity of response inhibition and interference control.
AB  - This study investigated the internal reliability, temporal stability and
      plasticity of commonly used measures of inhibition-related functions. Stop
      signal, go/no-go, antisaccade, Simon, Eriksen flanker, Stroop and Continuous
      Performance tasks were administered twice to 23 healthy participants over a
      period of approximately 11 weeks in order to assess test-retest correlations,
      internal consistency (Cronbach's alpha), and systematic between as well as within
      session performance changes. Most of the inhibition-related measures showed good
      test-retest reliabilities and internal consistencies, with the exception of the
      stop-signal reaction time measure, which showed poor reliability. Generally no
      systematic performance changes were observed across the two assessments with the
      exception of four variables of the Eriksen flanker, Simon and Stroop task which
      showed reduced variability of reaction time and an improvement in the response
      time for incongruent trials at second assessment. Predominantly stable
      performance within one test session was shown for most measures. Overall, these
      results are informative for studies with designs requiring temporally stable
      parameters e.g. genetic or longitudinal treatment studies.

PMID- 23174433
TI  - When do people cooperate? The neuroeconomics of prosocial decision making.
AB  - Understanding the roots of prosocial behavior is an interdisciplinary research
      endeavor that has generated an abundance of empirical data across many
      disciplines. This review integrates research findings from different fields into
      a novel theoretical framework that can account for when prosocial behavior is
      likely to occur. Specifically, we propose that the motivation to cooperate (or
      not), generated by the reward system in the brain (extending from the striatum to
      the ventromedial prefrontal cortex), is modulated by two neural networks: a
      cognitive control system (centered on the lateral prefrontal cortex) that
      processes extrinsic cooperative incentives, and/or a social cognition system
      (including the temporo-parietal junction, the medial prefrontal cortex and the
      amygdala) that processes trust and/or threat signals. The independent modulatory
      influence of incentives and trust on the decision to cooperate is substantiated
      by a growing body of neuroimaging data and reconciles the apparent paradox
      between economic versus social rationality in the literature, suggesting that we
      are in fact wired for both. Furthermore, the theoretical framework can account
      for substantial behavioral heterogeneity in prosocial behavior. Based on the
      existing data, we postulate that self-regarding individuals (who are more likely
      to adopt an economically rational strategy) are more responsive to extrinsic
      cooperative incentives and therefore rely relatively more on cognitive control to
      make (un)cooperative decisions, whereas other-regarding individuals (who are more
      likely to adopt a socially rational strategy) are more sensitive to trust signals
      to avoid betrayal and recruit relatively more brain activity in the social
      cognition system. Several additional hypotheses with respect to the neural roots
      of social preferences are derived from the model and suggested for future
      research.

PMID- 23174434
TI  - Spirituality and positive mental health.

PMID- 23174435
TI  - Brain structural abnormalities in obsessive-compulsive disorder: converging
      evidence from white matter and grey matter.
AB  - INTRODUCTION: Specific cortico-striato-thalamic circuits are hypothesised to
      underlie the aetiology of obsessive-compulsive disorder (OCD). However, findings
      from neuroimaging studies have been inconsistent. In the current study, we
      attempted to provide a complete overview of structural alterations in OCD by
      conducting signed differential mapping (SDM) meta-analysis on grey matter and
      white matter studies of patients with OCD based on voxel-based morphometry (VBM)
      studies and diffusion tensor imaging (DTI) studies. METHODS: Fifteen VBM and
      seven DTI case-control studies were included in this meta-analysis. SDM meta
      analyses were performed to assess grey matter volume and white matter integrity
      changes in OCD patients and healthy controls. RESULTS: We found that OCD patients
      had smaller grey matter volume than health controls in the frontal eye fields,
      medial frontal gyrus and anterior cingulate cortex. However, we showed that there
      was an increase in the grey matter volume in the lenticular nucleus, caudate
      nucleus and a small region in the right superior parietal lobule. OCD patients
      also had a lower fractional anisotropy (FA) in the cingulum bundles, inferior
      fronto-occipital fasciculus, and superior longitudinal fasciculus, while
      increased FA in the left uncinate fasciculus. CONCLUSIONS: The current findings
      confirm the structural abnormalities of cortico-striato-thalamic circuits in OCD.

PMID- 23174436
TI  - Pain symptoms in Malay patients with major depression.
AB  - OBJECTIVES: There is a strong association between depression and pain, which is
      influenced by various biological and psychological mechanisms. The objectives of
      this study were to assess the prevalence and severity of pain symptoms among
      patients with major depression; and to determine the correlation between pain
      with clinical variables, neurotic pathology and severity of depression. METHODS:
      Fifty-one Malay patients with major depressive disorder without psychotic feature
      enrolled for the study. They were assessed with the Hamilton Rating Scale for
      Depression (HAM-D), Brief Pain Inventory (BPI) and Crown Crisp Experiential Index
      (CCEI). RESULTS: The majority (80.4%) of the subjects had experienced pain, but
      overall severity of the pain was mild (33.3%). There were no statistically
      significant differences in socio-demographic variables with the status of pain.
      The prevalence of pain was significantly higher in patients who were still
      depressed (p<0.05), had anxious depression (p<0.05) and those with prominent
      somatic symptoms of anxiety (SOM) (p<0.05). The severity of pain was
      significantly correlated with neuroticism, the severity of depression (HAM-D
      total score) and high scores on SOM, DEP and FFA subscales of the CCEI. Among the
      three, the DEP subscale had the highest correlation with severity of pain.
      CONCLUSIONS: The somatising patients were heterogeneous group. The pain symptoms
      were common in severe mixed anxiety-depression, predisposed by the underlying
      neurotic pathology. Neuroticism and high scores on SOM, DEP and FFA subscales of
      the CCEI contributed significantly to the pathogenesis of depressed Malay
      patients with pain symptoms.

PMID- 23174437
TI  - Pathway to psychiatric care in a tertiary mental health facility in Jaipur,
      India.
AB  - PURPOSE: This study was planned to evaluate the pathway to care of mentally ill
      patients attending a tertiary mental health facility in Jaipur to highlight the
      difficulties of mentally ill and their relatives in accessing appropriate care.
      METHODS: Seventy-six patients, who attended the Out Patient Department of
      Psychiatry of a tertiary care hospital in Jaipur, India for the first time, were
      enrolled in this study. The family members of the patients were interviewed to
      evaluate the pathway to care using the Encounter form developed by the WHO.
      RESULTS: The patients were predominantly young adults, male, from rural, agrarian
      but educated background and a majority of them presented with psychotic
      illnesses. It was seen that there were five major gateways to care of the
      mentally ill in the region, Faith healers being the most popular portal of care.
      The median duration of untreated illness (DUI) was 6 months, and subjects had
      already visited, 2 carers before visiting any mental health professional. The
      median monetary cost of the pathway was Rs. 3565. Patients suffering from
      psychotic illnesses presented earlier. Those who used psychiatric services as
      first portal of care had different socio-demographic variables as compared to
      clients who used other services. CONCLUSION: This pathway to psychiatric care
      study in Jaipur, India demonstrated that referral pathway heavily relies on faith
      healers. The study indicates possible fields and gives indications, underlining
      the importance of improving awareness campaigns that will facilitate the
      recognition of psychiatric disorders.

PMID- 23174438
TI  - Quality of life in anxiety disorders: its relation to work and social functioning
      and dysfunctional cognitions: an exploratory study from India.
AB  - The aim of the study was to examine quality of life, functioning, disability,
      work and social adjustment, depression, anxiety and dysfunctional cognitions in
      patients with anxiety disorders. One hundred patients with anxiety disorders and
      98 non-clinical participants were recruited for the study. A cross sectional
      design was adopted. The participants were assessed on the WHOQoL-BREF, Global
      Assessment of Functioning (GAF), Sheehan Disability Scale (SDS), the Work and
      Social Adjustment Scale (WSAS) and Dysfunctional Attitudes Scale (DAS). Data was
      analyzed using descriptive statistics, Mann-Whitney test, Spearman's Rho and
      regression analysis. Patients with anxiety disorders reported significantly lower
      quality of life than the community sample (df=98, p<.001). A shorter duration of
      illness was associated with lower quality of life. QoL was significantly
      correlated with severity of anxiety, depression and stress as well as with
      measures of disability and adjustment. Partial correlations indicated that
      depression did not significantly impact the relationship between work and social
      adjustment and QoL. Work and social adjustment, depression and dysfunctional
      cognitions emerged as significant predictors of QoL. The findings of the study
      are discussed in the light of existing research and the implications for future
      interventions are highlighted.

PMID- 23174439
TI  - Are there different neural mechanisms responsible for three stages of weight gain
      development in anti-psychotic therapy: temporally based hypothesis.
AB  - Weight gain as a result of atypical anti-psychotic treatment is a common issue
      with different atypical anti-psychotic treatments causing differing magnitudes of
      weight gain. Although differing amounts of weight gain result from different
      atypical agents little is known about the temporal course of weight gain in anti
      psychotic treatment. Specifically is the time course of weight gain comparable
      across different agents. Therefore this article reviews the temporal course of
      weight gain for three common atypical anti-psychotics namely; clozapine,
      olanzapine and risperidone. It is evident that all three of these agents exhibit
      similar although at distinct magnitudes temporal courses of weight gain. That is
      an initial rapid increase from baseline to 3 months (stage 1), a steady increase
      from 3 months to 18 months (stage 2) and a plateau after this point (stage 3)
      with continued anti-psychotic treatment. It is postulated that each of these
      stages of weight gain result from distinct neural mechanisms. The hypothesized
      neural correlates for each stage of weight gain are reviewed and discussed. The
      article concludes with recommendations for future research.

PMID- 23174440
TI  - Subjective models of psychological disorders: mental health professional's
      perspectives.
AB  - This exploratory study is an extension of previous studies which have applied
      personal construct theory (PCP) methodology toward a better understanding of the
      structure and dynamics of multidisciplinary mental (and physical) health care
      (Kirkcaldy and Pope, 1992; Kirkcaldy et al., 1993, 2000, 2005; Kirkcaldy and
      Siefen, 1999). In this study we wanted to use similar cluster statistical
      analyses, not unlike PCP analysis, to identify the diverse subjective models of
      psychological ailments such as anxiety, depression, psychosis, mania, obsessive
      compulsive disorder (OCD), post stress traumatic disorder (PTSD), etc., using not
      the idiosyncratic constructs generated by individual triadic element comparisons,
      but by selecting those constructs which have been clearly identified in various
      psychiatric and psychological rating scales (e.g. somatic preoccupation, social
      withdrawal, conceptual disorganization, hostility, disinhibition and
      controlling). Clinical experts (psychological psychotherapists, and medical
      psychotherapist and psychiatrist) each with over 25 years of clinical and
      research experience were required to complete the ratings of each disorder listed
      in terms of the pre-formulated behavioral, emotional and cognitive concepts. What
      emerged are several multivariate (grid) analyses based on mental health
      professionals' perception of diverse elements (disorders) and their
      interrelationship derived from the similarity of composite profiles of ill
      related constructs. Overall, the analyses revealed clear associations between the
      subjective evaluations of psychological ailments suggesting some uniformity in
      mental health assessment of such disorders. The implications of these findings
      are discussed within the theoretical framework of improved mental health care.

PMID- 23174441
TI  - Electrophysiological examination of Formal Thought Disorder in schizophrenia.
AB  - Quantitave EEG profile was recorded for 60 age and sex matched drug free/naive
      schizophrenia patients, divided into two groups based on the presence and absence
      of Formal Thought Disorder (FTD) and a group of 30 matched healthy participants.
      Coherence and power spectrum analysis revealed that as compared to normal
      controls, schizophrenia patients with FTD had decreased regional power and intra
      hemispheric coherence; those without FTD had increased regional power and
      increased intra hemispheric coherence. Inter hemispheric coherence was greater in
      schizophrenia patients with FTD and lesser in those without FTD, as compared to
      healthy participants. The data were interpreted in terms of neural dis-connection
      which in FTD can be attributed to the existence of both a deficit and excess of
      neural connections, which compensate each other.

PMID- 23174442
TI  - Sikhism, spirituality and psychiatry.
AB  - Sikhism has millions of followers in India and among the Indian diaspora. As a
      religion it is relatively young but carries with it unique perspectives which are
      often not well known. The holy book of Sikhism, Guru Granth Sahib, is not only
      the last Guru, but also remained a key text for this religion. Using descriptions
      of the religion and its followers we attempt to understand the context of
      spirituality within this religion and attempt to apply it to clinical settings.
      We explored various texts to understand the notions of spirituality and ethics
      and directions for living one's life. We studied both the Gurumukhi version as
      well as the English translation of the Sikh holy text. In the context of history
      of the Sikhs, various descriptions related to mental well being were identified.
      In this paper we describe the history, development and the core values of the
      religion and we also review their role on psychiatric and mental health settings
      for managing Sikh patients. Guru Granth Sahib offers a very useful insight into
      what is understood by the term equivalent to depression and its phenomenology.
      The notions of dukh (loosely translated as pain, but can also mean sadness or
      suffering) and maya (illusion) and their role in daily living are also discussed.
      In this paper these descriptions are explored further and their importance
      explained.

PMID- 23174443
TI  - Assessing clinical implications of spiritual experiences.
AB  - Since spiritual experiences (SE) very often resemble dissociative and psychotic
      symptoms, there is a risk of misdiagnosis in both directions: labeling a healthy
      SE as a mental disorder or taking a mental disorder as an SE. There is a scarcity
      of well-controlled studies on this subject. The paper provides a brief overview
      of studies on dissociative and psychotic experiences in the non-clinical
      population, especially those occurring in spiritual populations. At the end, some
      guidelines are proposed to help clinical reasoning when making the differential
      diagnosis between healthy SE with psychotic and dissociative experiences and
      mental disorders that may resemble SE.

PMID- 23174444
TI  - Holistic health and well-being: a psycho-spiritual/religious and theological
      perspective.
AB  - Neuro-biological studies have established the perennial teaching of all the
      world's religious traditions that human persons are primarily religious/spiritual
      beings. They confirm that religion and spirituality are hardwired into the human
      brain and into human nature. The transcendental dimension of human nature demands
      that progress in man's ethical formation and inner growth is the most essential
      aspect of holistic health. Their experience of the divine led the Hindu sages to
      commit themselves to establish peace, happiness and well-being for all the human
      family and the universe. Judeo-Christian theology advocates that human beings
      created in the image of God have potential for theocentric-transcendence.
      Catholic theologians like St. Augustine propose that God has made humans for
      himself and that their hearts are restless until they rest in him. With the
      revolutionary shift in recent years from attacking faith and religion to the
      exploration of the benefits of spirituality and religion for human flourishing,
      the outstanding themes of Christian theology and other religious traditions
      became topics of research in health sciences. Interdisciplinary interaction will
      result in attaining a profound understanding of the human person and help him/her
      to achieve lasting fulfilment by adequately paying attention to the
      transcendental, religious and spiritual needs.

PMID- 23174445
TI  - Relational mindfulness, spirituality, and the therapeutic bond.
AB  - Mindfulness training, which emphasizes deliberate non-judgmental attention to
      present moment experiences, has become increasingly mainstream over the past
      several decades. With accumulating evidence for the physical and mental health
      benefits of mindfulness, it has been integrated into medical and psychological
      treatments and is increasingly accepted in the fields of psychology and
      psychiatry. However, several elements of mindfulness practice which potentially
      contribute to its benefits have been largely neglected. These include the
      connections between mindfulness, interpersonal relationships, spirituality, and
      the psychotherapeutic alliance. The emerging concept of "relational mindfulness"
      focuses attention on the oft-neglected interpersonal aspects of mindfulness
      practices. Relational mindfulness is potentially relevant to the
      psychotherapeutic process, due to its cultivation of the types of qualities that
      enhance the therapeutic relationship, including warmth, empathy, curiosity,
      acceptance, self-attunement, and emotional intelligence. In addition, mindfulness
      practices, especially relational ones, can contribute to the development of
      spiritual qualities, such as transcendence, boundlessness, ultimacy, and
      interconnectedness. Several recent studies suggest that meditation/mindfulness
      interventions may be explained and or enhanced by an emphasis on spiritual
      components. In this paper, we suggest that focusing on the oft-neglected
      relational and spiritual aspects of mindfulness practice has the potential to
      deepen its benefits, especially within the context of the psychotherapeutic
      relationship.

PMID- 23174446
TI  - Controversy or consensus? Recommendations for psychiatrists on psychiatry,
      religion and spirituality.
AB  - OBJECTIVE: Although there is still a lot of controversy surrounding the debates
      on religion and psychiatry, working toward consensus based on clinical experience
      and research seems to be far more fruitful. DISCOURSE: The main idea in this
      contribution runs as follows. It is no longer appropriate to treat psychiatry and
      religion as enemies. It is argued here that they are in fact allies. This
      position is elucidated in the light of two statements. (1) The World Psychiatric
      Association, indeed representing world psychiatry, needs to change its position
      toward religion and psychiatry. It should do so by crossing narrow-minded
      scientific boundaries like reductionist and materialistic boundaries. (2) Science
      and religion should not be regarded as opposing adversaries against each other,
      but as allies against nonsense and superstition. CONCLUSION: Two recommendations
      are formulated. First, science-and-religion, and in our case psychiatry-and
      religion, is not purely about description based on gathering evidence, systematic
      empirical testing and mathematical modeling. We need an approach of both
      descriptive and prescriptive aspects of our daily reality, not only how our world
      is, but also how it should be. Secondly, science-and-religion, in our case
      psychiatry-and-religion as allies should formulate sensible criteria and develop
      an appropriate attitude to discernment based on intellectual, moral and spiritual
      sincerity.

PMID- 23174447
TI  - Interview by Russell D'Souza.

PMID- 23174448
TI  - How to give an effective presentation.

PMID- 23174449
TI  - Successful treatment of atypical depression with amisulpride: a case report.

PMID- 23174450
TI  - Frequency and clinical features of borderline personality disorder in adolescent
      suicide attempts in Japan.

PMID- 23174451
TI  - Torticollis after low-dose aripiprazole administration in a Thai schizophrenia
      patient.

PMID- 23174452
TI  - Broad-based with a cutting edge: the evolution and growth of NIMHANS.
AB  - The National Institute of Mental Health and Neuro-Sciences (NIMHANS) in
      Bangalore, India began as the lunatic asylum, in 1848, when a separate asylum to
      care for the mentally ill was approved by Sir Mark Cubbon, Commissioner of Mysore
      in the Pettah area of Bangalore. After the transfer of power from the British to
      the Kingdom of Mysore in 1881, it became, for a while, the only asylum to be
      supported by a native kingdom. A larger mental hospital, in the light of the
      expanding population of Mysore, was thought essential by the 1920's, when the
      Maharaja of Mysore approved the decision to build a new asylum. This was finally
      completed in 1937, and by then had been renamed as the Mysore State Mental
      Hospital. The hospital, and its staff, was recommended as the first institution
      to begin training specialists in psychiatry and related mental health fields,
      after Independence, in 1953, when it was renamed the All-India Institute of
      Mental Health. It now houses the Department of Psychiatry at NIMHANS. The asylum
      architecture, horticultural layout, high standards of mental health care and
      emphasis on scientific training initiated in the early part of the last century
      continue to date and many of its alumni hold distinguished positions all over the
      world.

PMID- 23174453
TI  - Bringing out the leader in you--Malaysian Psychiatric Association Leadership
      Certification for Early Career Psychiatrists.

PMID- 23174454
TI  - [Morbidity and mortality in HIV-infected patients in the Military Hospital in
      Libreville (Gabon)].
AB  - OBJECTIVE: To study the morbidity and mortality of HIV-infected patients at the
      military hospital in Libreville (Gabon). MATERIALS & METHODS: A retrospective
      study of the clinical records of 289 HIV-positive patients hospitalized in the
      department of internal medicine between January 2008 and December 2010. RESULTS:
      The patient's median age was 40 years (range: 18-70). The principal presenting
      complaints were fever (82%), weight loss (76.47%) and coughing (26.64%). Median
      time from symptom onset to consultation was 150 days (1-365). The predominant
      opportunistic diseases were oropharyngeal candidiasis (71.62%), all forms of
      tuberculosis (26.29%) and cerebral toxoplasmosis (23.87%). The median CD4
      lymphocyte count was 177/mm(3 )(1-590). In-hospital mortality was 27.68%. The
      factors associated with death were long time to consultation and severe
      immunosuppression (CD4 count <100/mm(3)). CONCLUSION: Despite increased
      awareness, lateness of diagnosis and thus of treatment persist, and AIDS remains
      one of the principal causes of morbidity and mortality in Gabon.

PMID- 23174455
TI  - Alkaline transition of horse heart cytochrome c in the presence of ZnO
      nanoparticles.
AB  - The effect of zinc oxide nanoparticles (ZnO NPs) on cytochrome c (cyt c) in
      alkaline pH was studied with absorption spectroscopy and UV circular dichroism
      (CD). Spectral data from UV-vis spectroscopy and circular dichroism indicate only
      small changes in the native structure of the protein at neutral pH after the
      interaction with ZnO nanoparticles. The stability around the heme crevice of cyt
      c and therefore the switch of the axial ligand Met80 to Lys which occurs in
      conditions of higher pH was proven following the interaction of cytochrome c with
      ZnO nanoparticles. The formation of cyt c-ZnO NPs complex based on electrostatic
      attraction was accompanied by a significant increase in the apparent pKa constant
      of the alkaline transition of cyt c.

PMID- 23174456
TI  - Bisphenol A affects gene expression of gonadotropin-releasing hormones and type I
      GnRH receptors in brains of adult rare minnow Gobiocypris rarus.
AB  - Recent studies support the notion that endocrine disrupting chemicals (EDCs)
      could affect the reproductive regulations of the neuroendocrine system. The
      objectives of the present study were to determine whether the weak estrogenic
      chemical, bisphenol A (BPA), disrupts gonadotropin-releasing hormone (GnRH)
      system by altering the transcription of GnRHs and GnRH receptor (GnRHR) genes in
      adult rare minnow Gobiocypris rarus. In the present study, the histological
      examination of the ovary after 35-day BPA exposure at 15 MUg/L demonstrated the
      perturbing effects of environmentally relevant BPA on the ovarian development in
      G. rarus. In addition mRNA expression of ovarian P450 aromatase in both ovaries
      and testes were significantly down-regulated by 15 MUg/L BPA. GnRH2, GnRH3,
      GnRHR1A and GnRHR1B gene were identified in G. rarus. The expression patterns of
      GnRHs and GnRHR1s were analyzed in various tissues of G. rarus by quantitative
      real-time PCR. GnRHs and GnRHR1s were all predominantly expressed in the brains.
      Both GnRH3 and GnRHR1A were significantly upregulated in the brains of female
      exposed to 15 MUg/L BPA for 35 days. It would suggest a potential negative
      feedback in the GnRH system in response to the disturbance of downstream of the
      brain-pituitary-gonadal axis. Collectively, the present findings suggest that the
      transcripts of some key genes in the neuroendocrine system can be used as
      critical biomarkers in endocrine disruption assays of teleost fish.

PMID- 23174457
TI  - Mn2+ modulates the kinetic properties of an archaeal member of the PLL family.
AB  - Recently we reported on the characterization of an archaeal member of the
      amidohydrolase superfamily, namely Sulfolobus acidocaldarius lactonase, showing
      low but significant and extremely thermostable paraoxonase activity. This enzyme,
      that we have named SacPox, is a member of the new described family of
      phosphotriesterase-like lactonases (PLLs). In this family the binuclear metal
      centre, which is involved in the catalytic machinery, has been poorly studied up
      to now. In this work we describe the expression of the protein in presence of
      different metals showing Mn(2+) to support the higher activity. The enzyme has
      been over-expressed, purified and characterized as a Mn(2+)-containing enzyme by
      inductive plasma coupled mass spectrometry (ICP-MS), showing also surprising
      kinetic differences in comparison with the cadmium-containing enzyme. The Mn(2+)
      containing enzyme was about 30-fold more efficient with paraoxon as substrate and
      more stable than the Cd(2+) counterpart, even though the Mn(2+) affinity for the
      binuclear metal centre is apparently lower. These results increase our knowledge
      of the biochemical characteristics of SacPox mainly with regard to the metal-ions
      modulation of function.

PMID- 23174458
TI  - Assessment of the dining environment on and near the campuses of fifteen post
      secondary institutions.
AB  - OBJECTIVE: The present study evaluated the restaurant and dining venues on and
      near post-secondary campuses varying in institution size. DESIGN: The Nutrition
      Environment Measures Survey for Restaurants (NEMS-R) was modified to evaluate
      restaurants as fast food, sit down and fast casual; and campus dining venues as
      dining halls, student unions and snack bar/cafe's. ANOVA with post hoc Tukey's B
      and T tests were used to distinguish differences between dining venues and
      associated institutions by size. SETTING: The study was conducted at fifteen US
      post-secondary institutions, 2009-2011. SUBJECTS: Data presented are from a
      sample of 175 restaurants and sixty-eight on-campus dining venues. RESULTS: There
      were minimal differences in dining halls by institution size, although medium
      sized institutions as compared with small-sized institutions offered
      significantly more healthful side dish/salad bar items. Dining halls scored
      significantly higher than student unions or snack bar/cafe's on healthful
      entre'es, side dish/salad bar and beverages offerings, but they also had the most
      barriers to healthful dietary habits (i.e. all-you-can-eat). No differences were
      found by restaurant type for NEMS-R scores for total restaurant dining
      environment or healthful entre'es and barriers. Snack bars had more healthful
      side dishes (P50?002) and fast-food restaurants had the highest level of
      facilitators (i.e. nutrition information; P50?002). CONCLUSIONS: Based on this
      evaluation in fifteen institutions, the full campus dining environment provides
      limited support for healthy eating and obesity prevention. The quality of campus
      dining environments can be improved via healthful offerings, providing nutrition
      information and other supports to facilitate healthy eating and prevent unwanted
      weight gain.

PMID- 23174459
TI  - Complex visual illusions in a patient with pituitary apoplexy.

PMID- 23174460
TI  - The role of social media networks in psychotic disorders: a case report.
AB  - We report the case of a young man diagnosed with schizophrenia who presented with
      stalking behaviors that may have been caused by problematic use or participation
      in social media networks (SMN). We review the possible role of SMN in the
      formation of his romantic delusion and offer suggestions for clinicians around
      incorporation of SMN questions into assessments. It is imperative to identify
      populations at risk of SMN-related stalking behaviors to stratify mental health
      resources and interventions. Additional studies are needed to further clarify the
      role of SMN in psychotic disorders. 

PMID- 23174461
TI  - Prospective findings from the 1993 Pelotas (Brazil) birth cohort study.

PMID- 23174462
TI  - Interventions using new digital media to improve adolescent sexual health: a
      systematic review.
AB  - New digital media (e.g., the Internet, text messaging, and social networking
      sites [SNS]) have dramatically altered the communication landscape, especially
      for youth. These communication platforms present new tools for engaging youth in
      sexual health promotion and risk reduction. We searched eight public databases
      across multiple disciplines for all peer-reviewed studies published between
      January 2000 and May 2011 that empirically evaluated the impact of digital media
      based interventions on the sexual health knowledge, attitudes, and/or behaviors
      of adolescents aged 13-24 years. Of 942 abstracts, 10 met inclusion criteria.
      Seven studies were conducted in the United States. Eight described Web-based
      interventions, one used mobile phones, and one was conducted on an SNS. Two
      studies significantly delayed initiation of sex, and one was successful in
      encouraging users of an SNS to remove sex references from their public profile.
      Seven interventions significantly influenced psychosocial outcomes such as condom
      self-efficacy and abstinence attitudes, but at times the results were in
      directions unexpected by the study authors. Six studies increased knowledge of
      HIV, sexually transmitted infections, or pregnancy. This area of research is
      emerging and rapidly changing. More data from controlled studies with longer (>1
      year) follow-up and measurement of behavioral outcomes will provide a more robust
      evidence base from which to judge the effectiveness of new digital media in
      changing adolescent sexual behavior.

PMID- 23174463
TI  - Moderators of treatment effectiveness for war-affected youth with depression in
      northern Uganda.
AB  - PURPOSE: As we build the evidence base of interventions for depression among war
      affected youth, it is critical to understand factors moderating treatment
      outcomes. The current study investigated how gender and history of abduction by
      Lord's Resistance Army rebels moderated treatment outcomes for war-affected
      youth. METHODS: The study-a three-armed, randomized, controlled trial-was
      conducted with internally displaced war-affected adolescents in northern Uganda.
      Participants with significant depression symptoms (N = 304; 57% female; 14-17
      years of age) were randomly assigned to an interpersonal psychotherapy group (IPT
      G), a creative play/recreation group, or a wait-list control condition. Secondary
      analyses were conducted on data from this randomized controlled trial. RESULTS: A
      history of abduction by Lord's Resistance Army rebels was reported by 42% of the
      sample. Gender and abduction history interacted to moderate the effectiveness of
      IPT-G for the treatment of depression. In the IPT-G intervention arm, treatment
      effectiveness was greatest among female subjects without an abduction history,
      with effect size = 1.06. IPT-G was effective for the treatment of depression for
      both male and female subjects with a history of abduction (effect size = .92 and
      .50, respectively). Male subjects with no abduction history in IPT-G showed no
      significant improvement compared with those in the control conditions.
      CONCLUSIONS: Abduction history and gender are potentially important moderators of
      treatment effects, suggesting that these factors need to be considered when
      providing interventions for war-affected youth. IPT-G may be an effective
      intervention for female subjects without an abduction history, as well as for
      both male and female former child soldiers, but less so for male subjects without
      an abduction history.

PMID- 23174465
TI  - Examining the effect of maternal sexual communication and adolescents'
      perceptions of maternal disapproval on adolescent risky sexual involvement.
AB  - PURPOSE: To examine the influence of maternal sexual communication during early
      adolescence on three adolescent sexual risk behaviors (assessed 5-6 years later)
      in relation to adolescents' perceptions of maternal disapproval of [their] sexual
      involvement and contraceptive use. METHODS: Using data from waves 1 and 3 of the
      National Longitudinal Study of Adolescent Health (Add Health), we distinguish
      between youth who reported being virgins from those who reported having had sex
      by the time maternal sexual communication was assessed. RESULTS: Frequency of
      maternal sexual communication has a significant influence on adolescents'
      lifetime number of sexual partners, but its effect is moderated by adolescents'
      perceptions of maternal disapproval of contraceptive use. This relationship holds
      regardless of whether the adolescent was a virgin or not at the time of the
      communication. When occurring in the context of adolescent-perceived maternal
      nondisapproval, greater frequency of maternal sexual communication is associated
      with a higher likelihood of having multiple sexual partners. Greater frequency of
      maternal sexual communication was also associated with inconsistent condom use
      and positive sexually transmitted infection diagnosis among adolescents who were
      sexually experienced at baseline and who perceived maternal disapproval of
      contraceptive use. CONCLUSIONS: These findings emphasize the need to evaluate the
      effect of maternal sexual communication on adolescent risky sexual behaviors in
      relation to the value context of these discussions as well as the sexual status
      of the adolescent.

PMID- 23174464
TI  - Linkage to care for HIV-positive adolescents: a multisite study of the adolescent
      medicine trials units of the adolescent trials network.
AB  - PURPOSE: To understand linkage to care practices at sites providing clinical
      services to newly diagnosed HIV-positive adolescents. METHODS: Qualitative
      analysis of detailed interviews conducted with 28 personnel involved in linkage
      to care at 15 sites providing specialty care to HIV-positive adolescents.
      RESULTS: We showed that multiple models exist for linkage to care, and that both
      formal and informal community relationships are important for successful linkage
      to care. Stigma was seen as a universal issue, enhancing the importance of the
      balance of confidentiality and social support. Barriers to care, such as mental
      health issues, substance use, and transportation, are common. CONCLUSIONS: We
      conclude that the complexity of linkage to care requires thought and planning as
      HIV testing is expanded to lower-risk populations.

PMID- 23174467
TI  - Improving the implementation of a condom availability program in urban high
      schools.
AB  - PURPOSE: We conducted an intervention to improve the implementation of a high
      school condom availability program, and evaluated its effect on students'
      awareness of the program and acquisition of condoms. METHODS: Twelve public high
      schools in the Los Angeles, CA area participated, half each in the intervention
      and control conditions. Project staff facilitated intervention schools' self
      assessment of compliance with the school district's condom availability policy,
      creating an action plan by determining which mandatory program elements were
      lacking and identifying steps to improve compliance. Staff provided technical
      assistance and follow-up to assist schools in improving program implementation.
      From 2005 to 2009 (T1-T5), 29,823 students were randomly selected by classroom
      and they completed surveys. We tested for changes in students' awareness and
      acquisition of condoms over time between conditions using mixed model logistic
      regression analyses. Records of condom orders by schools also were reviewed.
      RESULTS: Awareness increased significantly among intervention versus control
      participants from T1 to T3 (adjusted odds ratio [AOR]: 1.28; 95% confidence
      interval [CI]: 1.01, 1.62), T4 (AOR: 2.17; 95% CI: 1.70, 2.76), and T5 (AOR:
      2.78; 95% CI: 2.18, 3.56). Acquisition of condoms increased significantly among
      intervention versus control participants from T1 to T4 (AOR: 1.69; 95% CI: 1.23,
      2.32) and T5 (AOR: 1.81; 95% CI: 1.32, 2.49). Results were similar across gender
      and different levels of sexual experience. Orders of condoms increased markedly
      in intervention schools by T5. CONCLUSIONS: Feasible minor enhancements to condom
      availability program implementation improved program delivery, resulting in
      increased student awareness of the program and acquisition of condoms.

PMID- 23174466
TI  - Association between sex partner meeting venues and sexual risk taking among urban
      adolescents.
AB  - PURPOSE: To increase understanding of the association between sexual partner
      meeting venue types (school, through friends or family, organized groups, public
      places, or on the street) and sexual risk taking among urban youths. METHODS:
      Data were from 17- to 18-year-old youths who reported having had sex (n = 1,656)
      by the time they participated in the 2008-2009 follow-up of a multicomponent
      alcohol preventive intervention, Project Northland Chicago. We used logistic
      regression to assess the association between partner meeting venue and sexual
      risk taking. RESULTS: Approximately 20% of Chicago adolescents met their most
      recent sex partner on the street or in public places. Adolescents who met their
      partner in a public place, rather than in school, were more likely to report
      having >= 3 years age-discordant partner (women: odds ratio [OR] = 7.7, 95%
      confidence interval [CI] = 3.3-17.7; men: OR = 2.7, 95% CI = 1.1-6.6], alcohol
      use before sex (women: OR = 3.4, 95% CI = 1.8-6.5; men: OR = 2.4, 95% CI = 1.3
      4.4), casual partner (women: OR = not significant; men: OR = 2.4, 95% CI = 1.3
      4.5), anal sex (women: OR = not significant; men: OR = 2.4, 95% CI = 1.2-4.9),
      and unprotected sex (women: OR = 1.7, 95% CI = 1.0-2.7; men: OR = 1.9, 95% CI =
      1.1-3.4). Meeting partners on the street was associated with increased
      probability of alcohol use before sex (women: OR = 2.2, 95% CI = 1.1-4.3; men: OR
      = 2.1, 95% CI = 1.0-4.6), age-discordant partnerships among women (OR = 14.2, 95%
      CI = 6.4-31.4), and casual sex partners among men (OR = 2.5, 95% CI = 1.4-4.8).
      CONCLUSIONS: Targeting sexual risk taking with partners selected from public
      places or the street may improve adolescent HIV preventive interventions.

PMID- 23174468
TI  - Effects of a natural community intervention intensifying alcohol law enforcement
      combined with a restrictive alcohol policy on adolescent alcohol use.
AB  - PURPOSE: Determining whether intensified inspections on alcohol retailers,
      combined with a policy withdrawing liquor licenses if retailers are fined twice
      per annum, is effective in reducing adolescents' odds to initiate weekly drinking
      and drunkenness. Causal pathways by which the intervention was assumed to work
      were tested. METHODS: A longitudinal (2008, 2009, and 2010) quasi-experimental
      comparison group design including two Dutch communities, one intervention and one
      comparison, was used. Outcomes were assessed by following a cohort of 1,327
      adolescents (aged 13-15 years at baseline). RESULTS: The intervention resulted in
      increased retail inspections but only seven sanctions and no repeated sanctions
      in 1 year. The intervention did not reduce adolescents' odds to initiate weekly
      drinking. Weekly drinking adolescents in the intervention community were at
      reduced risk to initiate drunkenness. This effect was not mediated by smaller
      increases in the frequency of adolescents' alcohol purchases or their perceived
      ease of purchasing alcohol. CONCLUSIONS: Intensified enforcement was effective in
      preventing adolescent drunkenness. No mediating causal pathways were detected.
      Effectiveness of enforcement could be increased by adopting enforcement methods
      with a high likelihood of apprehension, increasing social support for restrictive
      measures, and mobilizing the community to be more outspoken against adolescent
      (heavy) drinking.

PMID- 23174469
TI  - Trait mindfulness helps shield decision-making from translating into health-risk
      behavior.
AB  - PURPOSE: The cognitive tendency toward mindfulness may influence the enactment of
      health and risk behaviors by its bringing increased attention to and awareness of
      decision-making processes underlying behavior. The present study examined the
      moderating effect of trait mindfulness on associations between intentions to
      smoke (ITS)/smoking refusal self-efficacy (SRSE) and smoking frequency. METHODS:
      Self-reports from Chinese adolescents (N = 5,287; mean age = 16.2 years, standard
      deviation = .7; 48.8% female) were collected in 24 schools. Smoking frequency was
      regressed on latent factor interactions Mindful Attention Awareness Scale*ITS and
      Mindful Attention Awareness Scale*SRSE, adjusting for school clustering effects
      and covariates. RESULTS: Both interaction terms were significant in cross
      sectional analyses and showed that high ITS predicted higher smoking frequency
      among those low, relative to high, in trait mindfulness, whereas low SRSE
      predicted higher smoking frequency among those low, relative to high, in trait
      mindfulness. CONCLUSIONS: Findings suggest trait mindfulness possibly shields
      against decision-making processes that place adolescents at risk for smoking.

PMID- 23174470
TI  - ADHD knowledge, perceptions, and information sources: perspectives from a
      community sample of adolescents and their parents.
AB  - PURPOSE: The chronic illness model advocates for psychoeducation within a
      collaborative care model to enhance outcomes. To inform psychoeducational
      approaches for ADHD, this study describes parent and adolescent knowledge,
      perceptions, and information sources and explores how these vary by
      sociodemographic characteristics, ADHD risk, and past child mental health service
      use. METHODS: Parents and adolescents were assessed 7.7 years after initial
      school district screening for ADHD risk. The study sample included 374
      adolescents (56% high and 44% low ADHD risk) aged, on average, 15.4 (standard
      deviation = 1.8) years, and 36% were African American. Survey questions assessed
      ADHD knowledge, perceptions, and cues to action and elicited used and preferred
      information sources. Multiple logistic regression was used to determine potential
      independent predictors of ADHD knowledge. McNemar tests compared information
      source utilization against preference. RESULTS: Despite relatively high self
      rated ADHD familiarity, misperceptions among parents and adolescents were common,
      including a sugar etiology (25% and 27%, respectively) and medication overuse
      (85% and 67%, respectively). African American respondents expressed less ADHD
      awareness and greater belief in sugar etiology than Caucasians. Parents used a
      wide range of ADHD information sources, whereas adolescents relied on social
      network members and teachers/school. However, parents and adolescents expressed
      similar strong preferences for the Internet (49% and 51%, respectively) and
      doctor (40% and 27%, respectively) as ADHD information sources. CONCLUSIONS:
      Culturally appropriate psychoeducational strategies are needed that combine
      doctor-provided ADHD information with reputable Internet sources. Despite time
      limitations during patient visits, both parents and teens place high priority on
      receiving information from their doctor.

PMID- 23174471
TI  - The effects of lisdexamfetamine dimesylate on driving behaviors in young adults
      with ADHD assessed with the Manchester driving behavior questionnaire.
AB  - PURPOSE: Young adults with ADHD have been shown to be at increased risk for
      impairment in driving behaviors. Although stimulant medications have proven
      efficacy in reducing ADHD symptomatology, there is limited knowledge as to their
      effects on driving behavior. The focus of this report is on assessing the impact
      of lisdexamfetamine dimesylate (LDX) on driving behaviors in young adults with
      ADHD using a validated driving behavior questionnaire. METHODS: This assessment
      was carried out in the context of a randomized, double-blind, 6-week, placebo
      controlled, parallel-design study of LDX versus placebo. Subjects were 61
      outpatients of both sexes, 18-26 years of age, who met Diagnostic and Statistical
      Manual of Mental Disorders, fourth edition, criteria for ADHD. Subjects were
      randomized to receive LDX or placebo for 6 weeks. Driving behavior was assessed
      at baseline and at the end of treatment using a U.S. version of the Manchester
      Driving Behavior Questionnaire (DBQ). RESULTS: Highly significant improvements
      were documented on LDX, over placebo, in driving behaviors assessed through the
      DBQ in measures of driving errors, driving lapses, and a trend toward fewer
      driving violations. There were no meaningful associations between these DBQ
      results and previously documented changes in a laboratory driving simulation
      paradigm or with improvement in symptoms of ADHD assessed through the ADHD rating
      scale. CONCLUSIONS: LDX treatment was associated with significant improvements in
      self-reported driving behaviors that were independent of improvement in symptoms
      of ADHD. These results suggest that LDX may reduce behaviors associated with
      driving risks in young adults with ADHD.

PMID- 23174472
TI  - A cross-sectional and longitudinal study of travel by walking before and after
      school among eighth-grade girls.
AB  - PURPOSE: To examine "travel by walking" (TBW) before and after school among
      eighth-grade girls. METHODS: Participants attended 36 middle schools from
      Arizona, Maryland, Minnesota, Louisiana, California, and South Carolina
      participating in the Trial of Activity for Adolescent Girls. The cross-sectional
      sample consisted of 3,076 eighth-grade girls, and the longitudinal sample
      included 1,017 girls who participated in both sixth and eighth grades. Before- or
      after-school TBW status was determined from the 3-Day Physical Activity Recall.
      The main outcomes were body mass index and physical activity, which was measured
      by accelerometry, estimated for total physical activity (light, moderate,
      vigorous) and moderate-to-vigorous physical activity (MVPA). RESULTS: Eighth
      grade girls who reported TBW had 4 more minutes (95% confidence interval = 2.1
      6.1) of MVPA before and after school than nonwalkers, and 2 more minutes of MVPA
      (95% confidence interval = 1.1-3.1) on an average weekday. In the longitudinal
      sample, girls who reported TBW before and after school in both sixth and eighth
      grades (consistent walkers) accumulated more minutes of MVPA for an average
      weekday than inconsistent walkers in both sixth (27 +/- 2.2 vs. 25 +/- 1.9
      minutes; p = .03) and eighth (28 +/- 2.6 vs. 25 +/- 2.3 minutes; p = .003)
      grades. There were no differences in body mass index by walking status.
      CONCLUSIONS: Adolescent girls who reported TBW before and after school
      accumulated more minutes of MVPA than nonwalkers. Efforts to prevent the decline
      in walking to school in middle school girls could contribute to their overall
      physical activity.

PMID- 23174473
TI  - Daily morning running for 3 weeks improved sleep and psychological functioning in
      healthy adolescents compared with controls.
AB  - PURPOSE: To compare sleep electroencephalographic patterns and psychological
      functioning of healthy adolescents running regularly in the mornings with those
      of control subjects. Although several studies have shown that regular moderate-to
      vigorous exercise is related to favorable sleep and psychological functioning in
      adolescents, research on the effectiveness of short interventions is more
      limited. METHODS: Fifty-one adolescents (mean age = 18.30 years; 27 female [53%])
      took part in the study; they were randomly assigned either to a running or to a
      control group. The running group went running every morning for 30 minutes at
      moderate intensity during weekdays for 3 consecutive weeks. Sleep
      electroencephalographic patterns and psychological functioning were assessed in
      both groups before and after the 3-week period. All participants also kept a
      sleep log for 3 weeks. RESULTS: Objective sleep improved (slow-wave sleep
      increased; sleep onset latency decreased) in the running group compared with the
      control group. Subjective sleep quality, mood, and concentration during the day
      improved, whereas sleepiness during the day decreased. CONCLUSIONS: Thirty
      minutes of running in the morning during weekdays for 3 consecutive weeks
      impacted positively on sleep and psychological functioning in healthy adolescents
      compared with control subjects. Running is inexpensive and easy to implement
      during school schedules, and as both objective and subjective improvements were
      observed within 3 weeks, regular physical exercise should be promoted.

PMID- 23174474
TI  - The role of daily activities in youths' stress physiology.
AB  - PURPOSE: This study examined links between diurnal patterns of the stress hormone
      cortisol and time spent by adolescents in nine common daily activities. METHODS:
      During eight consecutive nightly telephone interviews, 28 youths (n = 12 girls),
      10-18 years of age, reported their daily activities. On 4 days, four saliva
      samples were also collected and assayed for cortisol. Multilevel models assessed
      within- and between-person associations between time in each activity and
      cortisol area under the curve (AUC), cortisol awakening response (CAR), morning
      peak (30 minutes after wake up), and daily decline (morning peak to bedtime).
      RESULTS: Links with AUC were found for most activities; significant associations
      with cortisol rhythms suggested that most effects were due to anticipation of the
      day's activities. Specifically, on days when youths spent more time than usual on
      video games and television, they had lower AUCs, with lower morning peaks. Youths
      who spent more time reading (within-person) and in computer-related activities
      (between-person) had higher AUCs, with stronger CARs (within-person). Youths who
      slept more had lower AUCs, with lower morning peaks on both the between- and
      within-person levels. Amounts of time spent in clubs, and for older adolescents
      in sports, were also linked to lower AUCs. Finally, youths who spent more time in
      school/schoolwork had lower average AUCs, but on days when youths spent more time
      than usual in school, they had higher AUCs, stronger CARs, and steeper daily
      declines. CONCLUSION: Beyond their known implications for psychological
      adjustment, youths' everyday activities are linked to stress physiology.

PMID- 23174476
TI  - Preventive child health care findings on early childhood predict peer-group
      social status in early adolescence.
AB  - PURPOSE: A disputed social status among peers puts children and adolescents at
      risk for developing a wide range of problems, such as being bullied. However,
      there is a lack of knowledge about which early predictors could be used to
      identify (young) adolescents at risk for a disputed social status. The aim of
      this study was to assess whether preventive child health care (PCH) findings on
      early childhood predict neglected and rejected status in early adolescence in a
      large longitudinal community-based sample. METHODS: Data came from 898
      participants who participated in TRAILS, a longitudinal study. Information on
      early childhood factors was extracted from the charts of routine PCH visits
      registered between infancy and age of 4 years. To assess social status, peer
      nominations were used at age of 10-12 years. RESULTS: Multinomial logistic
      regression showed that children who had a low birth weight, motor problems, and
      sleep problems; children of parents with a low educational level (odds ratios
      [ORs] between 1.71 and 2.90); and those with fewer attention hyperactivity
      problems (ORs = .43) were more likely to have a neglected status in early
      adolescence. Boys, children of parents with a low educational level, and children
      with early externalizing problems were more likely to have a rejected status in
      early adolescence (ORs between 1.69 and 2.56). CONCLUSIONS: PCH findings on early
      childhood-on motor and social development-are predictive of a neglected and a
      rejected status in early adolescence. PCH is a good setting to monitor risk
      factors that predict the social status of young adolescents.

PMID- 23174475
TI  - Preconception health trajectories and birth weight in a national prospective
      cohort.
AB  - PURPOSE: This study was designed to assess the relationship between birth weight
      and prospectively measured trajectories of preconception health across
      adolescence and young adulthood in a diverse national cohort of young adult
      women. METHODS: Data came from Waves I (1994-1995), III (2001-2002), and IV (2007
      2008) of the National Longitudinal Study of Adolescent Health. Eligibility was
      restricted to all the singleton live births (n = 3,436) to female participants
      occurring between the Wave III (ages 18-26 years) and Wave IV (ages 24-32 years)
      interviews. Preconception cigarette smoking, overweight/obesity, adequate
      physical activity, heavy alcohol consumption, and fair/poor self-rated health
      were measured in adolescence (Wave I) and early adulthood (Wave III) and combined
      into four-category variables to capture the timing and sequencing of exposure.
      The outcome measure, birth weight, was classified as low (<2,500 g), normal
      (2,500-4,000 g), and macrosomic (>4,000 g). RESULTS: Multinomial logistic
      regression results indicated that adult-onset overweight significantly increased
      the odds of having a macrosomic birth (odds ratio = 1.56; 95% confidence interval
      = 1.02-2.38). CONCLUSIONS: This study provides new evidence about the influence
      of maternal body mass index trajectories on offspring birth weight. Adult-onset
      overweight/obesity during the transition to adulthood was common in the sample
      and increased the odds of subsequently delivering a macrosomic infant by 56%.
      This finding suggests that healthy weight promotion before this transition would
      confer intergenerational benefits, and supports recommendations for preconception
      care to address overweight/obesity.

PMID- 23174477
TI  - [Celedonio Calatayud-Costa and the birth of the specialty, the Spanish Society of
      Medical Radiology, and the journal: the beginning of a century of Spanish
      radiology].
AB  - Dr. Celedonio Calatayud-Costa, an eminent Spanish radiologist, electrical
      engineer, researcher, and co-founder of the Spanish Society of Electrical
      Engineering and Medical Radiology, was also the founder of the Spanish Journal of
      Electrical Engineering and Medical Radiology. The journal, the first journal
      dedicated specifically to the incipient specialty of electrology, from which
      radiology would later develop, was the official publication of that primordial
      Society, and was thus the first antecessor of Radiologia, which is today the
      official journal of the Spanish Society of Medical Radiology. This article
      analyzes the figure of Dr. Calatayud, based on the scant information available
      about him, in the centennial of the publication of his journal. Criticized by
      some and eulogized by others, knowledge about this controversial figure is
      essential to any understanding of the beginnings of the specialty and its
      scientific publication in Spain.

PMID- 23174478
TI  - Screening approach, optimisation and scale-up for chiral liquid chromatography of
      cathinones.
AB  - Screening approaches adopted in pharmaceutical companies for chiral LC method
      development may be quite complicated and sophisticated in order to guarantee a
      high success rate. However in other environments it may be of more value to
      assess how simple a screen might be used to still have a good chance of achieving
      success. The genuine need to develop chiral separations for the former 'legal
      high' drug mephedrone and related cathinones of topical interest presented a good
      opportunity to develop this theme. In initial work on mephedrone itself, no
      chiral separation was observed on Chirobiotic V, Cyclobond I 2000 DNP, Whelk-O1
      and AmyCoat using reversed phase mobile phases. However, using normal phase
      solvents, chiral separation was observed on all the chiral stationary phases
      (CSP) used except Chiralcel OJ-H. Of the chiral separations observed on
      RegisPack, RegisCell and Whelk-O1, some optimisation work was carried out on the
      latter two which had showed the greatest enantioselectivity. Following
      optimisation, the best enantioselectivity (1.59) and enantioresolution (5.90) was
      found with a 250 mm * 4.6 mm I.D. Whelk-O1 column using a propan-2-ol (IPA)
      hexane-trifluoroacetic acid (TFA)-triethylamine (TEA) (10:90:0.05:0.05, v/v/v/v)
      mobile phase. Subsequent screening on other cathinones was restricted to
      RegisPack, RegisCell and Whelk-O1 or equivalent phases with two mobile phases and
      this gave a very good success rate. Indeed it was possible to separate all six
      cathinones on one column, RegisCell, with one mobile phase, propan-2-ol-hexane
      TFA (15:85:0.1, v/v/v) but obviously it had been necessary to go through the 3
      column screen to arrive at this finding. While Whelk-O1 was not so successful,
      ease of optimisation on this phase was again a feature. To illustrate the
      applicability of these separations, it was shown that, as a basis for semi
      preparative work, the optimsed mephedrone separation on Whelk-O1 could be scaled
      up to a 2000MUl injection of a 1.0 mg ml(-1) solution in mobile phase (2.0mg on
      column) while still using the 250 mm * 4.6 mm I.D. analytical column.

PMID- 23174479
TI  - Special issue: risk assessment of undesirable substances in feed.

PMID- 23174480
TI  - Phenylbutyric acid protects against carbon tetrachloride-induced hepatic
      fibrogenesis in mice.
AB  - A recent report showed that the unfolded protein response (UPR) signaling was
      activated in the pathogenesis of carbon tetrachloride (CCl(4))-induced hepatic
      fibrosis. Phenylbutyric acid (PBA) is a well-known chemical chaperone that
      inhibits endoplasmic reticulum (ER) stress and unfolded protein response (UPR)
      signaling. In the present study, we investigated the effects of PBA on CCl(4)
      induced hepatic fibrosis in mice. All mice were intraperitoneally (i.p.) injected
      with CCl(4) (0.15 ml/kg BW, twice per week) for 8 weeks. In CCl(4)+PBA group,
      mice were i.p. injected with PBA (150 mg/kg, twice per day) from the beginning of
      CCl(4) injection to the end. As expected, PBA significantly attenuated CCl(4)
      induced hepatic ER stress and UPR activation. Although PBA alleviated, only to a
      less extent, hepatic necrosis, it obviously inhibited CCl(4)-induced tumor
      necrosis factor alpha (TNF-alpha) and transforming growth factor beta (TGF-beta).
      Moreover, PBA inhibited CCl(4)-induced hepatic nuclear factor kappa B (NF-kappaB)
      p65 translocation and extracellular signal-regulated kinase (ERK) and c-Jun N
      terminal Kinase (JNK) phosphorylation. Interestingly, CCl(4)-induced alpha-smooth
      muscle actin (alpha-SMA), a marker for the initiation phase of HSC activation,
      was significantly attenuated in mice pretreated with PBA. Correspondingly, CCl(4)
      induced hepatic collagen (Col)1alpha1 and Col1alpha2, markers for the
      perpetuation phase of HSC activation, were inhibited in PBA-treated mice.
      Importantly, CCl(4)-induced hepatic fibrosis, as determined using Sirius red
      staining, was obviously attenuated by PBA. In conclusion, PBA prevents CCl(4)
      induced hepatic fibrosis through inhibiting hepatic inflammatory response and HSC
      activation.

PMID- 23174481
TI  - Role of Nrf2 antioxidant defense in mitigating cadmium-induced oxidative stress
      in the olfactory system of zebrafish.
AB  - Exposure to trace metals can disrupt olfactory function in fish leading to a loss
      of behaviors critical to survival. Cadmium (Cd) is an olfactory toxicant that
      elicits cellular oxidative stress as a mechanism of toxicity while also inducing
      protective cellular antioxidant genes via activation of the nuclear factor
      (erythroid-derived 2)-like 2 (Nrf2) pathway. However, the molecular mechanisms of
      Cd-induced olfactory injury have not been characterized. In the present study, we
      investigated the role of the Nrf2-mediated antioxidant defense pathway in
      protecting against Cd-induced olfactory injury in zebrafish. A dose-dependent
      induction of Nrf2-regulated antioxidant genes associated with cellular responses
      to oxidative stress was observed in the olfactory system of adult zebrafish
      following 24h Cd exposure. Zebrafish larvae exposed to Cd for 3h showed increased
      glutathione S-transferase pi (gst pi), glutamate-cysteine ligase catalytic
      subunit (gclc), heme oxygenase 1 (hmox1) and peroxiredoxin 1 (prdx1) mRNA levels
      indicative of Nrf2 activation, and which were blocked by morpholino-mediated Nrf2
      knockdown. The inhibition of antioxidant gene induction in Cd-exposed Nrf2
      morphants was associated with disruption of olfactory driven behaviors, increased
      cell death and loss of olfactory sensory neurons (OSNs). Nrf2 morphants also
      exhibited a downregulation of OSN-specific genes after Cd exposure. Pre
      incubation of embryos with sulforaphane (SFN) partially protected against Cd
      induced olfactory tissue damage. Collectively, our results indicate that
      oxidative stress is an important mechanism of Cd-mediated injury in the zebrafish
      olfactory system. Moreover, the Nrf2 pathway plays a protective role against
      cellular oxidative damage and is important in maintaining zebrafish olfactory
      function.

PMID- 23174483
TI  - Steady-state MEG responses elicited by a sequence of amplitude-modulated short
      tones of different carrier frequencies.
AB  - The auditory steady-state response (ASSR) is a weak potential or magnetic
      response elicited by periodic acoustic stimuli with a maximum response at about a
      40-Hz periodicity. In most previous studies using amplitude-modulated (AM) tones
      of stimulus sound, long lasting tones of more than 10 s in length were used.
      However, characteristics of the ASSR elicited by short AM tones have remained
      unclear. In this study, we examined magnetoencephalographic (MEG) ASSR using a
      sequence of sinusoidal AM tones of 0.78 s in length with various tone frequencies
      of 440-990 Hz in about one octave variation. It was found that the amplitude of
      the ASSR was invariant with tone frequencies when the level of sound pressure was
      adjusted along an equal-loudness curve. The amplitude also did not depend on the
      existence of preceding tone or difference in frequency of the preceding tone.
      When the sound level of AM tones was changed with tone frequencies in the same
      range of 440-990 Hz, the amplitude of ASSR varied in a proportional manner to the
      sound level. These characteristics are favorable for the use of ASSR in studying
      temporal processing of auditory information in the auditory cortex. The lack of
      adaptation in the ASSR elicited by a sequence of short tones may be ascribed to
      the neural activity of widely accepted generator of magnetic ASSR in the primary
      auditory cortex.

PMID- 23174482
TI  - Technical advances in the characterization of the complexity of sleep and sleep
      disorders.
AB  - The current clinical standard for quantifying sleep physiology is the laboratory
      polysomnogram, from which basic sleep-wake stages are determined. However, the
      complexity of sleep physiology has inspired alternative metrics that are
      providing additional insights into the rich dynamics of sleep. Electro
      encephalography, magneto-encephalography, and functional magnetic resonance
      imaging represent advanced imaging modalities for understanding brain dynamics.
      These methods are complemented by autonomic measurements that provide additional
      important insights. We review here the spectrum of approaches that have been
      leveraged towards improved understanding of the complexity of sleep. 

PMID- 23174484
TI  - [Acute myocardial infarction in Djibouti: 2-year prospective study].
AB  - OBJECTIVES: Acute myocardial infarction (AMI) is a life-threatening emergency. In
      Africa, the increasing prevalence of cardiovascular risk factors is leading to an
      epidemiological transition. No data have yet been reported about AMI in Djibouti.
      PATIENTS AND METHODS: This study prospectively included all patients with acute
      coronary syndrome and persistent ST segment elevation admitted to the emergency
      department of Bouffard Military Hospital in Djibouti from January 2009 through
      December 2010. It analyzed their clinical data and management. RESULTS: The study
      included 35 patients. Their mean age was 52 +/- 11 years [range: 29-76]. The sex
      ratio was 7.7 (men/women). Cardiovascular risk factors were: hypercholesterolemia
      (83%), tobacco use (60%), khat chewing (57%), diabetes (49%), hypertension (46%),
      and heredity (20%). AMI was anterior in 40% of cases. Fifteen patients (43%)
      arrived within 12 hours after the onset of symptoms (average 5 hours);
      thrombolysis was successful for 11 of them (73%). Seven patients (20%) died over
      the entire follow-up (11.3 +/- 9 months), 5 within the first month. Mortality was
      significantly associated with diabetes (p<0.01), initial severe clinical
      complications (p<0.01) and initial low left ventricular ejection fraction (p<10(
      6)). CONCLUSION: Patients with AMI in Djibouti are 10 to 15 years younger than in
      Western countries. Their high level of cardiovascular risk is remarkable. Khat
      use did not significantly affect prognosis. The high mortality rate was similar
      to rates reported before the percutaneous coronary angioplasty era.

PMID- 23174485
TI  - Ultra-sensitive conductometric detection of heavy metals based on inhibition of
      alkaline phosphatase activity from Arthrospira platensis.
AB  - This study is based on the conductometric measurement of alkaline phosphatase
      activity (APA) from the cyanobacterium, Arthrospira platensis, called Spirulina.
      Cyanobacterium cells were directly immobilized, by physical adsorption, on the
      ceramic part of gold interdigitated transducers. This activity was inhibited in
      the presence of heavy metals and a variation of the local conductivity was
      measured after addition of the substrate. The Michaelis-Menten constant (Km) was
      evaluated to be 0.75 mM through a calibration curve of the substrate, disodium 4
      nitrophenylphosphate p-nitrophenyl phosphate (pNPP). Inhibition of APA was
      observed with cadmium and mercury with a detection limit of 10(-20) M. The half
      maximal inhibitory concentration (IC50) was determined at 10(-19) M for Cd(2+)
      and 10(-17) M for Hg(2+), and the binding affinity of heavy metal (Ki) was equal
      to the IC50. On the sensor surface, scanning electron microscopy (SEM) images
      revealed a remarkable evolution of the cyanobacterium's external surface that was
      attributable to the first defense mechanism against toxic heavy metals in trace.
      This effect was also confirmed through the important increase of response time
      tau(90%) recorded for APA response towards the substrate pNPP after cell exposure
      to metallic cations. Lifetime of the Spirulina-based biosensor was estimated to
      be more than 25 days.

PMID- 23174486
TI  - Effects of cardiac resynchronization therapy on left ventricular mass and wall
      thickness in mild heart failure patients in MADIT-CRT.
AB  - BACKGROUND: The effect of cardiac resynchronization therapy (CRT) on left
      ventricular wall thickness and left ventricular mass (LVM) is unknown.
      OBJECTIVES: To evaluate the effects of CRT on septal and posterior wall thickness
      (SWT and PWT) and LVM in patients with left bundle branch block (LBBB) and non
      LBBB vs implantable cardioverter-defibrillator patients and to assess the
      relationship between CRT-induced changes and cardiac events. METHODS: We
      investigated 843 patients with LBBB and 366 patients with non-LBBB enrolled in
      the Multicenter Automatic Defibrillator Implantation Trial - Cardiac
      Resynchronization Therapy (MADIT-CRT) trial to analyze changes in SWT, PWT, and
      LVM at 12 months and subsequent outcome. The primary end point was heart failure
      or death; secondary end points included ventricular tachycardia, ventricular
      fibrillation, or death. RESULTS: In LBBB patients, reduction in SWT, PWT, and LVM
      was more pronounced in CRT defibrillator (CRT-D) than in implantable cardioverter
      defibrillator (SWT:-6.7% +/- 4.4% vs-1.0% +/- 1.9%; PWT:-6.4% +/- 4.3% vs-0.8% +/
      1.9%; LVM:-23.6% +/- 9.9% vs-5.1% +/- 5.1%; P<.001 for all). In CRT-D patients
      with non-LBBB, LVM reduction was less pronounced; however, changes in SWT and PWT
      were comparable. Changes in LVM correlated with changes in left ventricular end
      diastolic volume. In CRT-D patients with LBBB, reduction in SWT and LVM was
      associated with reduction in heart failure/death (SWT: hazard ratio 0.94; 95%
      confidence interval 0.89-0.99 per percent change; P = .03) and ventricular
      tachycardia/ventricular fibrillation/death (SWT: hazard ratio 0.95; 95%
      confidence interval 0.91-1.00; P = .04). CRT-D patients with non-LBBB did not
      show favorable reduction in clinical or arrhythmic end points related to changes
      in SWT, PWT, or LVM. CONCLUSIONS: CRT-D was associated with significant reduction
      in SWT, PWT, and LVM in patients with LBBB along with left ventricular volume
      changes and associated favorable clinical and arrhythmia outcomes.

PMID- 23174487
TI  - Risk of life-threatening cardiac events among patients with long QT syndrome and
      multiple mutations.
AB  - BACKGROUND: Patients with long QT syndrome (LQTS) who harbor multiple mutations
      (i.e. >= 2 mutations in >= 1 LQTS-susceptibility gene) may experience increased
      risk for life-threatening cardiac events. OBJECTIVES: The present study was
      designed to compare the clinical course of LQTS patients with multiple mutations
      to those with a single mutation. METHODS: The risk for life-threatening cardiac
      events (comprising aborted cardiac arrest, implantable defibrillator shock, or
      sudden cardiac death) from birth through age 40 years, by the presence of
      multiple vs. single mutations, was assessed among 403 patients from the LQTS
      Registry. RESULTS: Patients with multiple mutations (n=57) exhibited a longer QTc
      at enrollment compared with those with a single mutation (mean +/- SD: 506 +/- 72
      vs. 480 +/- 56 msec, respectively; P=0.003) and had a higher rate of life
      threatening cardiac events during follow-up (23% vs. 11%, respectively; p=0.031).
      Consistently, multivariate analysis demonstrated that patients with multiple
      mutations had a 2.3-fold (P=0.015) increased risk for life threatening cardiac
      events as compared to patients with a single mutation. The presence of multiple
      mutations in a single LQTS gene was associated with a 3.2-fold increased risk for
      life threatening cardiac events (P=0.010) whereas the risk associated with
      multiple mutation status involving >1 LQTS gene was not significantly different
      from the risk associated with a single mutation (HR 1.7, P=0.26). CONCLUSIONS:
      LQTS patients with multiple mutations have a greater risk for life-threatening
      cardiac events as compared to patients with a single mutation.

PMID- 23174489
TI  - Introduction.The entire scope of clinical medicine is being transformed by the
      integration of molecular medicine.

PMID- 23174488
TI  - Plasma visfatin levels and gene expression in morbidly obese women with
      associated fatty liver disease.
AB  - OBJECTIVES: The few studies on the physiopathological role of visfatin in morbid
      obesity and the related metabolic diseases have led us to examine visfatin levels
      and its liver gene expression in morbidly obese women with non-alcoholic fatty
      liver disease (NAFLD). DESIGN AND METHODS: We examined the circulating levels of
      visfatin by ELISA in serum samples from 95 morbidly obese women (MO) (BMI>40
      kg/m(2)) who underwent bariatric surgery and 38 normal weight control women
      (BMI<25 kg/m(2)). We analysed visfatin liver and adipose tissue mRNA expression
      by RT-PCR. We evaluated the circulating levels and gene expression of
      adiponectin, resistin, RBP4, TNFalpha, IL6 and CRP. RESULTS: Serum visfatin was
      significantly higher in MO compared with controls, and also in MO with NAFLD was
      significantly higher than MO with normal liver. We found that NAFLD diabetic
      patients presented similar serum visfatin levels than non-diabetic. Serum
      visfatin correlated with IL6 (r=0.496; p<0.001) and CRP levels (r=0.241;
      p=0.049). Liver visfatin expression was significantly higher in MO compared to
      controls and was also significantly higher in MO with NAFLD than in MO with
      normal liver. Visfatin liver expression correlated positively with resistin
      (r=0.436, p=0.018) and TNFalpha expression (r=0.328, p=0.028). Visfatin
      expression in adipose tissues was similar among the MO groups analysed.
      CONCLUSION: Serum visfatin and its liver expression are higher in MO women with
      NAFLD, irrespective of the presence of diabetes. Serum visfatin and its liver
      expression correlate positively with pro-inflammatory factors. These findings
      suggest that visfatin may be a molecule related with fat inflammation in morbid
      obesity and fatty liver disease.

PMID- 23174490
TI  - Hereditary nonmelanoma skin cancer.
AB  - Cutaneous basal and squamous cell carcinomas are among the most frequent
      malignancies in the white population, with the annual incidence estimates ranging
      from 1 million to 3.5 million cases in the United States. These tumors can occur
      either sporadically or in the context of hereditary genodermatoses with cancer
      predisposition, such as basal cell nevus syndrome, xeroderma pigmentosum,
      epidermolysis bullosa, or oculocutaneous albinism. Different genes and signaling
      pathways have been shown to play a central role in the development and growth of
      these tumors. This article overviews the clinical features, diagnostic criteria,
      and the most recent data on genetic routes of the major hereditary syndromes
      predisposed to the development of nonmelanoma skin cancer.

PMID- 23174491
TI  - Molecular diagnostics in genodermatoses.
AB  - In recent years, there has been tremendous progress in elucidating the molecular
      bases of genodermatoses. The interface between genetics and dermatology has
      broadened with the identification of "new" heritable disorders, improved
      recognition of phenotypic spectrums, and integration of molecular and clinical
      data to simplify disease categorization and highlight relationships between
      conditions. With the advent of next-generation sequencing and other technological
      advances, dermatologists have promising new tools for diagnosis of
      genodermatoses. This article first addresses phenotypic characterization and
      classification with the use of online databases, considering concepts of clinical
      and genetic heterogeneity. Indications for genetic testing related to medical
      care and patient/family decision making are discussed. Standard genetic testing
      is reviewed, including resources for finding specialized laboratories, methods of
      gene analysis, and patient/family counseling. The benefits and challenges
      associated with multigene panels, array-based analysis (eg, copy number
      variation, linkage, and homozygosity), and whole-exome or whole-genome sequencing
      are then examined. Specific issues relating to molecular analysis of mosaic skin
      conditions and prenatal/preimplantation diagnosis are also presented. Use of the
      modern molecular diagnostics described herein enhance our ability to counsel,
      monitor, and treat patients and families affected by genodermatoses, with broader
      benefits of providing insights into cutaneous physiology and multifactorial skin
      disorders.

PMID- 23174492
TI  - The role of molecular testing in the diagnosis of cutaneous soft tissue tumors.
AB  - A number of soft tissue tumors are characterized by recurring genetic
      abnormalities. The identification of these abnormalities has advanced our
      understanding of the biology of these tumors and has led to the development of
      molecular tests that are helpful diagnostically. This review will focus on the
      application of molecular diagnostic testing in select mesenchymal tumors of the
      dermis and subcutis.

PMID- 23174493
TI  - The role of molecular analysis in cutaneous lymphomas.
AB  - The purpose of this review is to summarize the most important molecular
      techniques for the diagnosis of cutaneous lymphomas. When making a diagnosis, we
      are looking for the solid clinicopathological correlation. Molecular analysis
      includes immunophenotyping and clonality analysis, and is important for 2
      principal reasons: (1) to confirm the diagnosis in cases where the clinical
      and/or pathological presentations are nondiagnostic, and (2) to further
      characterize the nature of the lymphoma. More specifically, we are trying to
      discern whether the lymphoma is primarily cutaneous or systemic with secondary
      skin involvement, and we are also attempting to subclassify the tumor. Recently,
      many techniques have provided a more accurate diagnosis of cutaneous lymphomas
      and some prognostic implications, including polymerase chain reaction,
      fluorescence in situ hybridization, and flow cytometry. Fluorescence in situ
      hybridization is not routinely used in the diagnosis of cutaneous lymphoma, but
      many studies have shown potential future applications in various areas. Other
      techniques, such as comparative genomic hybridization, are still confined to the
      research arena, but have added some insight into the molecular pathogenesis of
      cutaneous T-cell lymphoma.

PMID- 23174494
TI  - Polymerase chain reaction-based molecular diagnosis of cutaneous infections in
      dermatopathology.
AB  - Conventional methods, including microscopy, culture, and serologic studies, are a
      mainstay in the diagnosis of cutaneous infection. However, owing to limitations
      associated with these techniques, such as low sensitivity for standard microscopy
      and in the case of culture delay in diagnosis, polymerase chain-reaction based
      molecular techniques have taken on an expanding role in the diagnosis of
      infectious processes in dermatopathology. In particular, these assays are a
      useful adjunct in the diagnosis of cutaneous tuberculosis, atypical mycobacterial
      infection, leprosy, Lyme disease, syphilis, rickettsioses, leishmaniasis, and
      some fungal and viral infections. Already in the case of tuberculosis and
      atypical mycobacterial infection, standardized polymerase chain-reaction assays
      are commonly used for diagnostic purposes. With time, additional molecular-based
      techniques will decrease in cost and gain increased standardization, thus
      delivering rapid diagnostic confirmation for many difficult-to-diagnose cutaneous
      infections from standard formalin-fixed paraffin-embedded tissue specimens.

PMID- 23174495
TI  - Molecular diagnosis of infection-related cancers in dermatopathology.
AB  - The association between viruses and skin cancer is increasingly recognized in a
      number of neoplasms, that is, cutaneous squamous cell carcinoma, Kaposi sarcoma,
      nasopharyngeal carcinoma, and Merkel cell carcinoma, as well as hematolymphoid
      malignancies such as adult T-cell leukemia/lymphoma and NK/T-cell lymphoma (nasal
      type) and post-transplant lymphoproliferative disorders. Molecular assays are
      increasingly used to diagnose and manage these diseases. In this review,
      molecular features of tumor viruses and related host responses are explored. The
      tests used to identify such features are summarized. Evaluation of the utility of
      these assays for diagnosis and/or management of specific tumor types is
      presented.

PMID- 23174496
TI  - Update on the genetics of androgenetic alopecia, female pattern hair loss, and
      alopecia areata: implications for molecular diagnostic testing.
AB  - Androgenetic alopecia, female pattern hair loss, and alopecia areata are among
      the most common forms of nonscarring hair loss encountered in clinical practice.
      Although the exact pathogenesis of these forms of alopecia remains to be
      clarified, genetic factors appear to have a significant contribution to their
      pathogenesis. Current treatment strategies are limited and their effectiveness
      remains modest at best. This review summarizes the current purported pathogenesis
      and recent genetic discoveries relating to these forms of alopecia. The role of
      molecular diagnostic testing is also discussed in relation to its future clinical
      utility for the prediction of developing hair loss, the diagnosis of the type of
      alopecia, prediction of disease severity, development of novel therapeutic and
      preventative targeted treatments, as well as determination of response to
      therapy.

PMID- 23174497
TI  - Molecular platforms utilized to detect BRAF V600E mutation in melanoma.
AB  - Metastatic melanoma (MM) is a deadly skin disease refractory to standard
      chemotherapy. Despite numerous clinical and pathological parameters derived to
      guide patient management, clinical outcomes in melanoma patients remain difficult
      to predict. There is a critical need to delineate the important biomarkers
      typical of this disease. These biomarkers will ideally illuminate those key
      biochemical pathways responsible for the aggressive behavior of melanoma and, in
      the process, unveil new opportunities for the design of rational therapeutic
      interventions in high-risk patients. The most common recurring mutation in
      cutaneous melanoma is the prooncogenic BRAF V600E mutation that drives melanoma
      cell proliferation. The development of RAF inhibitors targeted against BRAF V600E
      mutant melanoma cells has revolutionized the treatment of MM. Clinical trials
      with BRAF inhibitor vemurafenib have shown objective clinical response and
      improved survival in patients with MM; therefore, knowledge of the molecular
      signature of melanoma in patients will be important in directing management
      decisions. Several molecular platforms exist to analyze the mutation status of
      melanoma. These include Sanger sequencing, pyrosequencing, allele-specific
      reverse transcriptase polymerase chain reaction, mass spectrometry base
      sequencing (Sequenom), high-resolution melting curve analysis, and next
      generation sequencing methods using microfluidics technology. The Food and Drug
      Administration has approved the cobas BRAF V600 Mutation Test developed by Roche
      to analyze BRAF mutation status in formalin-fixed paraffin-embedded tumor
      samples. The cobas Mutation Test has been designed specifically to detect BRAF
      V600E mutations, and the analytic performance of this assay has demonstrated >99%
      sensitivity in the detection of BRAF V600E mutation when compared with the Sanger
      sequencing method and confirmed with the next-generation sequencing 454
      pyrosequencing technology. The lower limit of detection of the percentage of
      mutant alleles in a tissue sample for the cobas test is less than 4%-5%. Some
      cross-reactivity with other variants of mutant BRAF was seen with the cobas V600
      platform; however, this clinical test offers highly sensitive reproducible BRAF
      V600E mutation analysis in formalin-fixed paraffin-embedded tumor samples.

PMID- 23174498
TI  - Molecular diagnostics for ambiguous melanocytic tumors.
AB  - Certain subsets of melanocytic neoplasms are difficult to classify because of
      conflicting histologic features and the existence of a poorly defined
      intermediate grade of melanocytic tumors. The integration of molecular diagnostic
      information with a histologic impression may contribute significantly toward
      improving classification. This review discusses the development of and advances
      in molecular techniques, including comparative genomic hybridization and
      fluorescence in situ hybridization (FISH) as diagnostic and prognostic tools for
      melanocytic neoplasms. Further, we discuss how specific molecular aberrations
      identified via FISH correlate with certain morphologies in melanocytic neoplasms.
      We also examine the prognostic value of FISH in intermediate-grade melanocytic
      tumors, particularly atypical Spitz tumors.

PMID- 23174499
TI  - Brief dynamic therapy and depression severity: a single-blind, randomized study.
AB  - BACKGROUND: Brief dynamic therapy (BDT) has been shown to be effective in
      treating depressive disorders. Nevertheless, whether its effect is related to the
      severity of depression is still unknown. The aim of this study was to analyze
      whether the efficacy of BDT is related to severity of depressive symptoms in
      patients with mild to moderate unipolar depressive disorders. METHODS: A
      randomized clinical trial compared BDT with brief supportive psychotherapy (BSP)
      in 88 outpatients with depressive disorders. Two subgroups of patients were
      considered for statistical analysis: with mild depressive disorders (HAM-D17
      baseline score: 8-13) and with moderate depressive disorders (HAM-D17 baseline
      score: 14-18). Patients were assessed at start of treatment (baseline-T0), at the
      end of treatment (T1) and at 6-month follow-up (T2). RESULTS: In the subgroup of
      patients with mild depressive disorders, no statistically significant differences
      emerged between the two treatments on all efficacy measures. In the subgroup of
      patients with moderate depressive disorders, the remission rates of patients
      treated with BDT were higher than those of patients treated with BSP at 6 month
      of follow-up (90.5% vs. 34.8%: p<.005). LIMITATIONS: The sample size was
      relatively small; a longer follow-up period should be considered to assess the
      efficacy of BDT in terms of prevention of recurrences. CONCLUSIONS: The efficacy
      of BDT in treating depressive disorders is higher in moderate than in mild
      depression.

PMID- 23174500
TI  - What predicts persistent depression in older adults across Europe? Utility of
      clinical and neuropsychological predictors from the SHARE study.
AB  - BACKGROUND: Depression in later life frequently persists and perpetuating factors
      are of immediate therapeutic relevance to clinicians. No studies of this scale
      have examined both clinical and neuropsychological predictors of persistent
      depression in a cross-national European context. METHODS: 4095 community dwelling
      older adults (>= 50 yr) with clinically signficant depression (EURO-D >= 4) from
      eleven European countries in the Survey of Heath, Ageing, and Retirement in
      Europe (SHARE) were followed for a median of 28 months. Logistic regression
      analyses were conducted to determine predictors of persistent depression.
      RESULTS: 2187 (53.4%) remained depressed at follow up. Independent predictors
      included: female gender, baseline functional impairment, functional decline,
      physical symptoms, past history of depression, increased severity of depression,
      early age of onset (< 50 yr), life events, financial distress and country of
      residence. Neuropsychological variables were associated with persistent
      depression but not independently of other variables. LIMITATIONS: The assessment
      of depression was by self-report and the data source did not contain a number of
      potentially relevant predictors. CONCLUSION: Individuals at risk of persistent
      depression may be identified and targeted for intervention. Therapeutic
      interventions should adopt a multimodal approach to optimise current function,
      prevent further functional decline and treat symptoms of depression. Country of
      residence may be associated with further modifiable variables.

PMID- 23174501
TI  - Coronary artery disease diagnosis by analysis of ECG depolarization.

PMID- 23174502
TI  - Author's response.

PMID- 23174503
TI  - A flash from the past: a case on long term follow-up of a "corridor" operation.
AB  - An electrophysiological study in a patient with a previous corridor operation was
      performed because of syncope. The atrial electrograms showed the persistence of
      the sinus rhythm in the right atrial corridor despite an organized atrial
      fibrillation in the left atrium. The first case described of a long term follow
      up in a corridor operation, one of the first described surgical approach for the
      treatment of atrial fibrillation, that gave the beginning to the non
      pharmacological approach of this arrhythmia.

PMID- 23174504
TI  - Canine distemper virus with the intact C protein has the potential to replicate
      in human epithelial cells by using human nectin4 as a receptor.
AB  - Recent outbreaks in monkeys have proven that canine distemper virus (CDV) causes
      diseases in a wide range of mammals. CDV uses SLAM and nectin4 as receptors to
      replicate in susceptible animals. Here, we show that human nectin4, but not human
      SLAM, is fully functional as a CDV receptor. The CDV Ac96I strain hardly
      replicated in nectin4-expressing human epithelial NCI-H358 cells, but readily
      adapted to grow in them. Unsurprisingly, no amino acid change in the H protein
      was required for the adaptation. The original Ac96I strain possessed a truncated
      C protein, and a subpopulation possessing the intact C protein was selected after
      growth in NCI-H358 cells. Other CDV strains possessing the intact C protein
      showed significantly higher growth abilities in NCI-H358 cells than the Ac96I
      strain with the truncated C protein. These findings suggest that the C protein is
      functional in human epithelial cells and critical for CDV replication in them.

PMID- 23174505
TI  - Identification of two functional nuclear localization signals in the capsid
      protein of duck circovirus.
AB  - The capsid protein (CP) of duck circovirus (DuCV) is the major immunogenic
      protein and has a high proportion of arginine residues concentrated at the N
      terminus of the protein, which inhibits efficient mRNA translation in prokaryotic
      expression systems. In this study, we investigated the subcellular distribution
      of DuCV CP expressed via recombinant baculoviruses in Sf9 cells and the DNA
      binding activities of the truncated recombinant DuCV CPs. The results showed that
      two independent bipartite nuclear localization signals (NLSs) situated at N
      terminal 1-17 and 18-36 amino acid residue of the CP. Moreover, two expression
      level regulatory signals (ELRSs) and two DNA binding signals (DBSs) were also
      mapped to the N terminus of the protein and overlapped with the two NLSs. The
      ability of CP to bind DNA, coupled with the karyophilic nature of this protein,
      strongly suggests that it may be responsible for nuclear targeting of the viral
      genome.

PMID- 23174506
TI  - Longitudinal study of seroprevalence and serostability of 34 human papillomavirus
      types in European organ transplant recipients.
AB  - Organ transplant recipients (OTR) are at increased risk of cutaneous squamous
      cell carcinoma, which may be related to reactivation of human papillomavirus
      (HPV) infections. Measurement of change in HPV antibodies after transplantation
      would help to explore this hypothesis. We measured antibodies to 34 HPV types on
      up to six occasions over 18 months in 441 OTRs from five European countries. At
      baseline (mean 24 days after transplantation), 80% of all OTRs were seropositive
      to at least one HPV type. The beta HPV genus had the highest seroprevalence
      (45%). For most HPV genera baseline seroprevalence peaked between 40 and 59 years
      old. Most OTRs retained their serostatus over time and antibody levels were
      stable. Seroprevalence in immunosuppressed OTRs is stable in the 18 months
      immediately after transplantation. Thus there is no short-term evidence that
      immunosuppression leads to new or reactivated skin infection with HPV sufficient
      to induce antibodies.

PMID- 23174507
TI  - Multiple antigen peptide consisting of B- and T-cell epitopes of F1 antigen of Y.
      pestis showed enhanced humoral and mucosal immune response in different strains
      of mice.
AB  - Yersinia pestis is a causative agent of plague. F1 and V antigen based vaccines
      have shown remarkable protection in experimental animals. In order to develop
      epitope based immunogen, three B and one T-cell epitopes of F1 antigen with
      palmitate residue at amino terminal were assembled on a lysine backbone as
      multiple antigen peptide (MAP or F1-MAP). MAP was characterized by SDS-PAGE,
      immunoblot and immunoreactivity with anti F1 sera. MAP was entrapped in PLGA
      (polylactide-co-glycolide) microparticles and humoral, mucosal immune responses
      were studied after intranasal immunization with/without CpG ODN 1826
      (CpG)/murabutide in different strains of mice. Serum and mucosal washes were
      measured for MAP specific IgG, IgA, sIgA and IgG subclasses in three strains of
      mice. F1-MAP showed high serum antibody and mucosal IgG and IgA peak antibody
      titers. MAP with CpG showed significantly high (p<0.001) peak antibody titer
      ranging from 102,400 to 204,800 for IgG and 6400 to 12,800 for IgA. High mucosal
      sIgA and its secretary component detection confirmed generation of mucosal
      response in intestinal and lung washes. MAP antisera also showed significant
      immunoreactivity with individual peptides. Moreover, antibody specific activity
      (IgG, IgA and sIgA) positively correlates with peak antibody titers.
      Predominantly IgG2a/IgG2b subclass was observed with CpG formulation but in other
      formulation a mixed IgG1 and IgG2a response was observed. The present study
      highlights the importance of multiple antigen peptide approach of F1-antigen with
      CpG as an alternative approach for subunit vaccine.

PMID- 23174508
TI  - The effect of phloretin on human gammadelta T cells killing colon cancer SW-1116
      cells.
AB  - OBJECTIVE: To explore the effect and mechanism of Phloretin on human gammadelta T
      cells killing colon cancer SW-1116 cells. METHODS: gammadelta T cells were
      amplified in vitro from human peripheral blood mononuclear cells through
      isopentenyl pyrophosphate method (IPP). After cocultured different concentrations
      of Phloretin with gammadelta T cells or SW-1116 cells for 48h respectively, MTT
      assay was used to test the growth curve of these two cells; Flow cytometry to
      test the expression of Granzyme B (GraB), perforin (PFP), CD107a and IFN-gamma of
      gammadelta T cells; Lactate dehydrogenase (LDH) release assay to test the
      cytotoxic activity of the gammadelta T cells on SW-1116 cells; and Western blot
      to test the Wnt3a expression of the gammadelta T cells. RESULTS: After cultured
      with IPP for ten days, the percentage of gammadelta T cells increased from 3.31+/
      3.00% to 78.40+/-10.30%. Compared to the control group, when the concentration of
      Phloretin increased from 2.35MUg/ml to 18.75MUg/ml, it could significantly
      proliferate the gammadelta T cell growth (P<0.05) and inhibit the growth of SW
      1116 cells in dose-response, and the expression of GraB, PFP, CD107a and Wnt3a
      significantly increased (P<0.05). Significant positive relationships were
      observed among CD107a and PFP, GraB, cytotoxicity (P<0.05). The percentage of IFN
      gamma producing gammadelta T cells treated with Phloretin was significantly
      higher than control group. CONCLUSION: Phloretin can enhance the killing effect
      of gammadelta T cells on SW-1116 cells; the mechanism may be that Phloretin could
      proliferate the gammadelta T cell growth, increase the expression of PFP and
      GraB, activate the Wnt signaling pathway, and produce higher level of IFN-gamma.
      Indeed CD107a expression probably correlates quite well with antitumor activity.

PMID- 23174509
TI  - Biochemical and functional characterization of recombinant fungal
      immunomodulatory proteins (rFIPs).
AB  - In this study, two novel FIPs have been identified and characterized. The first
      is FIP-nha, identified in the ascomycete Nectria haematococca, and as such, FIP
      nha would be the first FIP to be identified outside the order of Basidiomycota.
      The second is LZ-9, an LZ-8 like protein identified in Ganoderma lucidum.
      Recombinant FIPs (rFIPs) were produced in Pichia pastoris and purified using His
      affinity magnetic beads. The bioactive characteristics of FIP-nha and LZ-9 were
      compared to the well-known FIPs, LZ-8 from G. lucidum and FIP-fve from Flammulina
      velutipes, which were produced and purified using the same method. The produced
      rFIPs: rLZ-8, rLZ-9, rFIP-fve and rFIP-nha were investigated for their
      hemagglutinating activity which revealed that rLZ-8, rLZ-9 and rFIP-nha were able
      to agglutinate rabbit, mouse and sheep red blood cells while rFIP-fve only
      agglutinated rabbit red blood cells. None of the rFIPs were able to agglutinate
      human red blood cells unless the cells were trypsinized. In addition, all rFIPs
      were studied and compared to several lectins for their effect on Caco-2
      intestinal cell layer integrity using transepithelial electrical resistance
      (TEER) measurement. rLZ-9 appeared to have the highest effect in lowering TEER,
      similar to one of the tested lectins. Testing of rFIPs for their activation of
      inflammation-related genes of THP-1 macrophages showed rFIP-fve to be the
      strongest inducer of pro-inflammatory cytokine transcription. These results
      indicate that each rFIP has a unique bioactive profile as well as each lectin,
      creating the basis for further studies to relate structure to biological
      activity.

PMID- 23174510
TI  - Peripheral signalling involved in energy homeostasis control.
AB  - The alarming prevalence of obesity has led to a better understanding of the
      molecular mechanisms controlling energy homeostasis. Regulation of energy intake
      and expenditure is more complex than previously thought, being influenced by
      signals from many peripheral tissues. In this sense, a wide variety of peripheral
      signals derived from different organs contributes to the regulation of body
      weight and energy expenditure. Besides the well-known role of insulin and
      adipokines, such as leptin and adiponectin, in the regulation of energy
      homeostasis, signals from other tissues not previously thought to play a role in
      body weight regulation have emerged in recent years. The role of fibroblast
      growth factor 21 (FGF21), insulin-like growth factor 1 (IGF-I), and sex hormone
      binding globulin (SHBG) produced by the liver in the regulation of body weight
      and insulin sensitivity has been recently described. Moreover, molecules
      expressed by skeletal muscle such as myostatin have also been involved in adipose
      tissue regulation. Better known is the involvement of ghrelin, cholecystokinin,
      glucagon-like peptide 1 (GLP-1) and PYY(3-36), produced by the gut, in energy
      homeostasis. Even the kidney, through the production of renin, appears to
      regulate body weight, with mice lacking this hormone exhibiting resistance to
      diet-induced obesity. In addition, the skeleton has recently emerged as an
      endocrine organ, with effects on body weight control and glucose homeostasis
      through the actions of bone-derived factors such as osteocalcin and osteopontin.
      The comprehension of these signals will help in a better understanding of the
      aetiopathology of obesity, contributing to the potential development of new
      therapeutic targets aimed at tackling excess body fat accumulation.

PMID- 23174511
TI  - Nutrition and the HIV-associated lipodystrophy syndrome.
AB  - HIV-associated lipodystrophy syndrome (HALS), comprising metabolic and
      morphological alterations, is a known side effect of highly active antiretroviral
      therapy (HAART). Evidence for the role of nutrition in the management of the
      systemic parameters of HALS is currently limited. In the present paper we review
      the current knowledge base surrounding HALS, focusing particularly on the role of
      nutrition in mitigating the systemic parameters of the syndrome. Reported
      prevalence of HALS was found to vary from 9 to 83 % due to lack of a standardised
      definition, as well as variations in assessment methods and in the study
      population used. HALS is associated with both morphological (lipoatrophy,
      lipohypertrophy) and metabolic (dyslipidaemia, glucose intolerance, diabetes,
      hypertension, endothelial dysfunction and atherosclerosis) alterations, which may
      occur singly or in combination, and are associated with an increased risk of CVD.
      HAART-induced adipocyte inflammation, oxidative stress and macrophage
      infiltration, as well as altered adipocyte function and mitochondrial toxicity,
      have been shown to be central to the development of HALS. The adipocyte,
      therefore, represents a plausible target for treatment. Pharmacological and
      surgical treatment interventions have shown effect. However, their use is
      associated with numerous adverse effects and complications. Targeted lifestyle
      interventions may provide a useful alternative for managing HALS owing to their
      safety and tolerability. A Mediterranean-style diet has been found to be
      effective in improving the systemic parameters of HALS. Furthermore, the effects
      of n-3 PUFA supplementation are encouraging and future randomised controlled
      trials investigating the beneficial effects of n-3 PUFA in HALS are justified.

PMID- 23174512
TI  - The role of oxidative stress in postprandial endothelial dysfunction.
AB  - Endothelial dysfunction is a turning point in the initiation and development of
      atherosclerosis and its complications and is predictive of future cardiovascular
      events. Ingestion of high-carbohydrate or high-fat meals often results in
      postprandial hyperglycaemia and/or hypertriacylglycerolaemia that may lead to a
      transient impairment in endothelial function. The present review will discuss
      human studies evaluating the impact of high-carbohydrate and high-fat challenges
      on postprandial endothelial function as well as the potential role of oxidative
      stress in such postprandial metabolic alterations. Moreover, the present review
      will differentiate the postprandial endothelial and oxidative impact of meals
      rich in varying fatty acid types.

PMID- 23174513
TI  - Exercising control: exercise intention and perceived constraints in older adults
      with osteoarthritis.
AB  - PURPOSE OF THE STUDY: Maintaining perceived psychological control in older
      adulthood is beneficial for health, well-being, and adjustment to chronic
      illness. Theoretically, control over specific, personally meaningful domains
      should inform general control beliefs. Thus, the objective of the present study
      was to examine perceived control over the exercise domain (operationalized as
      exercise intention belief) for its ability to predict general control beliefs in
      a sample of older adults with chronic illness over 1 year. DESIGN AND METHODS:
      Longitudinal survey responses from 133 older adults with osteoarthritis (OA) were
      examined. RESULTS: Longitudinal hierarchical multiple regression analyses
      revealed that higher baseline exercise intention beliefs predicted a lower
      perception of constraints on control 9-12 months later, but did not predict
      changes in mastery beliefs. IMPLICATIONS: Results suggest that bolstering
      exercise intention beliefs may protect against age-related increases in
      psychological constraints on perceived control for older adults with OA.

PMID- 23174514
TI  - Drop out from out-patient mental healthcare in the World Health Organization's
      World Mental Health Survey initiative.
AB  - BACKGROUND: Previous community surveys of the drop out from mental health
      treatment have been carried out only in the USA and Canada. AIMS: To explore
      mental health treatment drop out in the World Health Organization World Mental
      Health Surveys. METHOD: Representative face-to-face household surveys were
      conducted among adults in 24 countries. People who reported mental health
      treatment in the 12 months before interview (n = 8482) were asked about drop out,
      defined as stopping treatment before the provider wanted. RESULTS: Overall, drop
      out was 31.7%: 26.3% in high-income countries, 45.1% in upper-middle-income
      countries, and 37.6% in low/lower-middle-income countries. Drop out from
      psychiatrists was 21.3% overall and similar across country income groups (high
      20.3%, upper-middle 23.6%, low/lower-middle 23.8%) but the pattern of drop out
      across other sectors differed by country income group. Drop out was more likely
      early in treatment, particularly after the second visit. CONCLUSIONS: Drop out
      needs to be reduced to ensure effective treatment.

PMID- 23174515
TI  - Cost-effectiveness of early intervention in first-episode psychosis: economic
      evaluation of a randomised controlled trial (the OPUS study).
AB  - BACKGROUND: Information about the cost-effectiveness of early intervention
      programmes for first-episode psychosis is limited. AIMS: To evaluate the cost
      effectiveness of an intensive early-intervention programme (called OPUS) (trial
      registration NCT00157313) consisting of enriched assertive community treatment,
      psychoeducational family treatment and social skills training for individuals
      with first-episode psychosis compared with standard treatment. METHOD: An
      incremental cost-effectiveness analysis of a randomised controlled trial,
      adopting a public sector perspective was undertaken. RESULTS: The mean total
      costs of OPUS over 5 years (?123,683, s.e. = 8970) were not significantly
      different from that of standard treatment (?148,751, s.e. = 13073). At 2-year
      follow-up the mean Global Assessment of Functioning (GAF) score in the OPUS group
      (55.16, s.d. = 15.15) was significantly higher than in standard treatment group
      (51.13, s.d. = 15.92). However, the mean GAF did not differ significantly between
      the groups at 5-year follow-up (55.35 (s.d. = 18.28) and 54.16 (s.d. = 18.41),
      respectively). Cost-effectiveness planes based on non-parametric bootstrapping
      showed that OPUS was less costly and more effective in 70% of the replications.
      For a willingness-to-pay up to ?50,000 the probability that OPUS was cost
      effective was more than 80%. CONCLUSIONS: The incremental cost-effectiveness
      analysis showed that there was a high probability of OPUS being cost-effective
      compared with standard treatment.

PMID- 23174516
TI  - Religion, spirituality and mental health: results from a national study of
      English households.
AB  - BACKGROUND: Religious participation or belief may predict better mental health
      but most research is American and measures of spirituality are often conflated
      with well-being. AIMS: To examine associations between a spiritual or religious
      understanding of life and psychiatric symptoms and diagnoses. METHOD: We analysed
      data collected from interviews with 7403 people who participated in the third
      National Psychiatric Morbidity Study in England. RESULTS: Of the participants 35%
      had a religious understanding of life, 19% were spiritual but not religious and
      46% were neither religious nor spiritual. Religious people were similar to those
      who were neither religious nor spiritual with regard to the prevalence of mental
      disorders, except that the former were less likely to have ever used drugs (odds
      ratio (OR) = 0.73, 95% CI 0.60-0.88) or be a hazardous drinker (OR = 0.81, 95% CI
      0.69-0.96). Spiritual people were more likely than those who were neither
      religious nor spiritual to have ever used (OR = 1.24, 95% CI 1.02-1.49) or be
      dependent on drugs (OR = 1.77, 95% CI 1.20-2.61), and to have abnormal eating
      attitudes (OR = 1.46, 95% CI 1.10-1.94), generalised anxiety disorder (OR = 1.50,
      95% CI 1.09-2.06), any phobia (OR = 1.72, 95% CI 1.07-2.77) or any neurotic
      disorder (OR = 1.37, 95% CI 1.12-1.68). They were also more likely to be taking
      psychotropic medication (OR = 1.40, 95% CI 1.05-1.86). CONCLUSIONS: People who
      have a spiritual understanding of life in the absence of a religious framework
      are vulnerable to mental disorder.

PMID- 23174517
TI  - Usage patterns of personal care products: important factors for exposure
      assessment.
AB  - Complete information regarding the use of personal care products (PCPs) by
      consumers is limited, but such information is crucial for realistic consumer
      exposure assessment. To fill this gap, a database was created with person
      oriented information regarding usage patterns and circumstances of use for 32
      different PCPs. Out of 2700 potential participants from the Netherlands, 516 men
      and women completed a digital questionnaire. The prevalence of use varied by
      gender, age, level of education and skin type. A high frequency of use was
      observed for some products (e.g. lip care products), while toothpaste, deodorant
      and day cream were generally used once or twice a day. The frequency of use for
      other PCPs varied over a wide range. The amounts of use varied largely between
      and within different product groups. Body lotion, sunscreen and after sun lotion
      were often applied on adjacent body parts. The majority of PCPs were applied in
      the morning, but some products, such as night cream and after sun, were
      predominantly applied in the evening or night. As expected, the participants used
      several PCPs simultaneously. The database yields important personalized exposure
      factors which can be used in aggregate consumer exposure assessment for
      substances that are components of PCPs.

PMID- 23174518
TI  - Chemical characterization, antioxidant and cytotoxic activities of Brazilian red
      propolis.
AB  - Propolis is known for a long time for its health benefits and biological
      activities. Here, the red variety from the northeast of Brazil was chemically
      analyzed and extracts were investigated regarding their antioxidant and antitumor
      activity. Hydroalcoholic extracts, obtained from the red propolis, revealed
      polyphenol content, 2,2-diphenyl-1-picrylhydrazyl scavenging potential and
      enzymatic activities for catalase-like and superoxide dismutase-like. Cytotoxic
      activity was evaluated for human laryngeal epidermoid carcinoma cell (Hep-2),
      human cervical adenocarcinoma (HeLa) and human normal epithelial embryonic kidney
      (Hek-293). Survival analysis for non-tumor cell line showed greater IC50 compared
      to tumor cell lines, suggesting an increased sensitivity that may correlate with
      the higher proliferative index of the tumor vs. normal cells. Our results
      indicate that the Brazilian red propolis is capable of inhibiting cancer cell
      growth and constitutes an excellent source of antioxidant and antitumor natural
      agent.

PMID- 23174519
TI  - An unusual marine envenomation following a rope contact: a report on nine cases
      of dermatitis caused by Pennaria disticha.
AB  - We would like to present the clinical course of nine patients who had an acute,
      painful dermatitis following contact with a rope used as a swimming area liner in
      the sea. The macroscopic and microscopic analysis of the fouling on the rope
      retrospectively, revealed Pennaria disticha as the causative organism. To our
      knowledge, there is no previous report on P. disticha envenomation in medical
      literature. P. disticha is a benthic hydrozoa belonging to Cnidaria phylum.
      Cnidaria are well known for their envenomation with their venomous organelle,
      "cnidocyst". The contact with cnidaria can result in a wide range of cytotoxic or
      anaphylactic reactions. While there is a large body of data in the literature
      from studies at molecular and cellular levels, there is limited data about the in
      vivo effects of cnidaria toxins. We think the clinical aspects of the
      dermatologic reactions caused by P. disticha and the diagnostic work-up to reveal
      the contamination on this unusual medium would be of interest to the readers.

PMID- 23174520
TI  - A prospective observational analysis of ambulation after motor vehicle
      collisions.
AB  - OBJECTIVES: Predicting injury patterns of patients based only on mechanism of
      injury is difficult and is well described in the literature. Characteristics of
      patients on-scene immediately following injury(ies) may lead to predicting injury
      patterns. Although reported frequently, the significance of victim ambulation
      after a motor vehicle crash is poorly understood. It was hypothesized that
      ambulation at the scene is not predictive of injury severity following a motor
      vehicle crash (MVC). METHODS: A prospective, cohort study of 117 consecutive
      injured patients who were ambulatory after MVCs were enrolled. Paramedics in a
      large urban Emergency Medical Services (EMS) system were mandated to document
      "ambulatory" or "nonambulatory" for motor vehicle collisions in order to complete
      their prehospital electronic medical records. This assured accuracy and
      completeness in the data collection. All charts were abstracted for trauma
      induced injury and imaging results. RESULTS: A total of 608 (10.9%) persons were
      ambulatory at the scene, of which 284 had an injury pattern documented in the
      prehospital or emergency department record. The average age was 35.9 (SD = 16.8)
      years, and 158 (55.6%) were male. A total of 707 injuries were identified in the
      284 patients who had sustained injuries. CONCLUSIONS: Ambulation after motor
      vehicle collisions appears to be only infrequently associated with major
      injuries, although this population still may present with significant injuries. A
      larger, prospective study is warranted.

PMID- 23174521
TI  - Zebrafish: a nontraditional model of traditional medicine.
AB  - With a modern rise in the use of traditional medicines has come a need for model
      organisms that are amenable not only to treatment with these remedies, but also
      to testing the large number of potential therapeutics this field presents. The
      high-fecundity and rapid generation time of the zebrafish makes it a natural
      candidate for this endeavor. Additionally, the zebrafish shares genetic, anatomic
      and physiologic homology to higher order vertebrates. This review surveys the
      present state of phytotherapy research utilizing the zebrafish model organism.
      The studies herein described utilize the zebrafish for investigating plant-based
      effectors of hypercholesterolemia, angiogenesis, Parkinson's and Alzheimer's. In
      addition to reviewing the present state of research in this area, the
      philosophical intersection of modern and traditional medical paradigms is
      discussed and future directions for investigations at this junction are
      suggested.

PMID- 23174522
TI  - Characterization of the aqueous extract of the root of Aristolochia indica:
      evaluation of its traditional use as an antidote for snake bites.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: The aqueous extract of the roots of Aristolochia
      indica is used as a decoction for the ailment of a number of diseases including
      snake bite treatment. Though the alcoholic extract of the different parts of the
      plant are well studied, information on the aqueous extract is limited. We have
      estimated aristolochic acid, different enzymes, enzyme inhibitors and anti-snake
      venom potency of its root extract. MATERIALS AND METHODS: Reverse phase-HPLC was
      used to quantify aristolochic acid. Zymography, DQ-gelatin assay and atomic force
      microscopy were done to demonstrate gelatinase and collagenase activities of the
      extract. SDS-PAGE followed by MS/MS analysis revealed the identity of major
      protein components. Toxicity of the extract was estimated on animal model.
      Interaction of the extract with Russell's viper venom components was followed by
      Rayleigh scattering and enzyme assay. RESULTS: The aristolochic acid content of
      the root extract is 3.08 +/- 1.88 * 10(-3)mg/ml. The extract possesses strong
      gelatinolytic, collagenase, peroxidase and nuclease activities together with l
      amino acid oxidase and protease inhibitory potencies. Partial proteomic studies
      indicated presence of starch branching enzymes as major protein constituent of
      the extract. The extract did not show any acute and sub-chronic toxicity in
      animals at lower doses, but high dose causes liver and kidney damage. The extract
      elongated duration of survival of animals after application of Russell's viper
      venom. CONCLUSIONS: Considering the low aristolochic acid content of the extract,
      its consumption for a short time at moderate dose does not appear to cause
      serious toxicity. Strong inhibition of l-amino acid oxidase may give partial
      relief from snake bite after topical application of the extract.

PMID- 23174523
TI  - Chylous ascites: Why exercise is bad for you.
AB  - INTRODUCTION: The development of chylous ascites is usually associated with
      trauma, iatrogenic or otherwise. Blunt abdominal trauma producing hyperextension
      or hyperflexion may cause disruption to lymphatic vessels causing chylous
      ascites. PRESENTATION OF CASE: This report describes the case of a 38-year-old
      gentleman who presented to the emergency department with severe abdominal pain
      after completing a triathlon. As the patient was in severe pain, an abdominal CT
      was performed which demonstrated a possible mid gut volvulus. Subsequent
      laparotomy noted a significant volume of intra-abdominal chyle with no other
      abnormalities. DISCUSSION: This is the first report of chylous ascites occurring
      without associated abdominal pathology after a period of strenuous exercise.
      CONCLUSION: Chylous ascites can occur as a result of hyperreflexion and
      hyperextension injuries sustained during strenuous exercise.

PMID- 23174524
TI  - An elective combined caesarean section and small bowel GIST resection during the
      third trimester of pregnancy: Report of a case.
AB  - INTRODUCTION: Gastro-Intestinal Stromal Tumours (GISTs) are rare with an
      estimated incidence of only 11-15 per million. In pregnancy, GISTs are an
      extremely rare occurrence and are thus complex to manage from an ethical,
      surgical and oncological perspective. PRESENTATION OF CASE: We present the first
      reported case in the literature of a successful combined lower segment caesarean
      section (LSCS) and a tumour resection in a 31-year-old pregnant patient
      presenting with a small bowel GIST. DISCUSSION: We compare and contrast our case
      with other reported cases of GIST resection in pregnancy and discuss the
      challenges faced by both patients and clinicians. CONCLUSION: Our case
      demonstrates that a combined LSCS and GIST resection is feasible. In addition,
      our case highlights the importance of both the multidisciplinary setting and the
      consideration of patients' wishes in the successful management of this complex
      group of patients.

PMID- 23174525
TI  - [Assessment of the management of cases of fever and malaria by general
      practitioners in the central Highlands of Madagascar, 2009-2010].
AB  - The aim of this study was to determine the frequency of confirmed malaria among
      patients with fever in the central Highlands of Madagascar, the clinical utility
      of treating this fever, and the involvement of community general practitioners in
      improving malaria management. This descriptive, prospective study took place from
      July 1, 2009, through June 30, 2010. Patients consulting for fever were
      classified into 2 groups: the first (G1) included all children younger than 5
      years and the second group (G2) children 5 years or older and adults. In G1, 1383
      cases of fever included 145 (10.5%) confirmed cases of malaria. The corresponding
      numbers in G2 were 1172 and 276 (23.5%). The prevalence of malaria was highest
      between December and May. In G1, the main clinical signs associated with a
      positive rapid diagnostic test (RDT) were pallor, jaundice, seizures, and failure
      to eat. In G2, a positive RDT was associated with pallor, coma, and jaundice.
      Treatment of patients with positive RDTs was based on quinine (51%) or
      artemisinin-based combination therapy (49%). Malaria remains endemic in the
      central Highlands of Madagascar. Efforts should be undertaken to improve
      prescription of antimalarial drugs.

PMID- 23174526
TI  - Kaempferol glycosides from the twigs of Cinnamomum osmophloeum and their nitric
      oxide production inhibitory activities.
AB  - In the present study, ethanolic extract of twigs from Cinnamomum osmophloeum led
      to isolate nine kaempferol glycosides including two new kaempferol triglycosides
      that were characterized as kaempferol 3-O-beta-D-xylopyranosyl-(1->2)-alpha-L
      arabinofuranosyl-7-O-alpha-L-rhamnopyranoside (1) and kaempferol 3-O-beta-D
      xylopyranosyl-(1->2)-alpha-L-rhamnopyranosyl-7-O-alpha-L-rhamnopyranoside (2).
      The structures of these compounds were assigned by the application of 1D and 2D
      NMR spectroscopy and other techniques. Among these nine compounds, kaempferol 7-O
      alpha-L-rhamnopyranoside (9) revealed inhibitory effect against LPS-induced
      production of nitric oxide in RAW 264.7 macrophages with an IC(50) value of 41.2
      MUM. It also slightly reduced PGE(2) accumulation by 26% at the concentration of
      50 MUM.

PMID- 23174527
TI  - Genetic drift influenza A(H3N2) virus hemagglutinin (HA) variants originated
      during the last pandemic turn out to be predominant in the 2011-2012 season in
      Northern Italy.
AB  - Influenza A(H3N2) virus is once again the predominant strain after the 2009
      pandemic. Its molecular epidemiology and phylogeny were investigated during the
      2011-2012 season in Northern Italy. The epidemiological and virological influenza
      surveillance was carried out within the framework of the Italian Influenza
      Surveillance Network. The hemagglutinin (HA) gene of the A(H3N2) viruses detected
      was analyzed by means of a time-scaled phylogenetic approach. In Northern Italy,
      the 2011-2012 epidemic wave was sustained almost exclusively by influenza A(H3N2)
      viruses (87.2% of total influenza virus detections). The consultation rates for
      influenza-like illness (ILI) in the age group >=65 years were 1.5 to 6-fold
      higher than those registered during the previous eight epidemics: A(H3N2) was the
      only virus identified in this group. The phylogenetic analysis of A(H3N2) viruses
      showed viruses belonging to the A/Victoria/208/2009 genetic clade, characterized
      by substitutions in HA antigenic sites with respect to the A/Perth/16/2009-like
      2011-2012 vaccine strain. About one-third of analyzed sequences fell into group 6
      and two thirds into group 3 (subdivided into 3A, 3B, and 3C). The time scale
      reconstruction of the phylogeny showed several independent introductions of
      A(H3N2) groups between summer and winter of 2011. However, the common origin of
      all the circulating A(H3N2) strains dated back to the 2009 pandemic period
      (November 2009). The time scale phylogenetic approach is of particular importance
      for the evaluation of the introduction and circulation of new variants in the
      area. Therefore, it should be implemented within the framework of influenza
      virological surveillance.

PMID- 23174528
TI  - Generalized Linear Model (GLM) framework for the association of host variables
      and viral strains with liver fibrosis in HCV/HIV coinfected patients.
AB  - Chronic hepatitis C virus (HCV) infection is the main cause of advanced and end
      stage liver disease world-wide, and an important factor of morbidity and
      mortality in Human Immunodeficiency virus-1 (HIV-1) co-infected individuals.
      Whereas the genetic variability of HCV has been studied extensively in
      monoinfected patients, comprehensive analyses of both patient and virus
      characteristics are still scarce in HCV/HIV co-infection. In order to find
      correlates for liver damage, we sought to analyze demographic, epidemiological
      and clinical features of HCV/HIV co-infected patients along with the genetic
      makeup of HCV (viral subtypes and lineage studied by nucleotide sequencing and
      phylogenetic analysis of the NS5B region). We used the Generalized Linear Model
      (GLM) methodology in order to integrate data from the virus and the infected host
      to find predictors for liver damage. The degree of liver disease was evaluated
      indirectly by means of two indexes (APRI and FIB-4) and accounting for the time
      since infection, to estimate fibrosis progression rates. Our analyses identified
      a reduced number of variables (both from the virus and the host) implicated in
      liver damage, which included the stage of HIV infection, levels of gamma-glutamil
      transferase and cholesterol, and some distinct HCV phylogenetic clades.

PMID- 23174529
TI  - Phagocyte dynamics in a highly regenerative urochordate: insights into
      development and host defense.
AB  - Phagocytosis is a cellular process by which particles and foreign bodies are
      engulfed and degraded by specialized cells. It is functionally involved in
      nutrient acquisition and represents a fundamental mechanism used to remove
      pathogens and cellular debris. In the marine invertebrate chordate Botryllus
      schlosseri, cell corpse engulfment by phagocytic cells is the recurrent mechanism
      of programmed cell clearance and a critical process for the successful execution
      of asexual regeneration and colony homeostasis. In the present study, we have
      utilized a naturally occurring process of vascular parabiosis coupled with
      intravascular microinjection of fluorescent bioparticles and liposomes as tools
      to investigate the dynamics of phagocyte behavior in real-time during cyclical
      body regeneration. Our findings indicate that B. schlosseri harbors two major
      populations of post-mitotic phagocytes, which display distinct phagocytic
      specificity and homing patterns: a static population that lines the circulatory
      system epithelia, and a mobile population that continuously recirculates
      throughout the colony and exhibits a characteristic homing pattern within
      mesenchymal niches called ventral islands (VI). We observed that a significant
      proportion of ventral island phagocytes (VIP) die and are engulfed by other VIP
      following takeover. Selective impairment of VIP activity curtailed zooid
      resorption and asexual development. Together, these findings strongly suggest
      that ventral islands are sites of phagocyte homing and turnover. As botryllid
      ascidians represent invertebrate chordates capable of whole body regeneration in
      a non-embryonic scenario, we discuss the pivotal role that phagocytosis plays in
      homeostasis, tissue renewal and host defense.

PMID- 23174530
TI  - CT appearance of common cosmetic and reconstructive surgical procedures and their
      complications.
AB  - In this review, we illustrate the spectrum of imaging features after plastic
      surgical procedures including transverse rectus abdominis myocutaneous flap, deep
      inferior epigastric perforators flap, latissimus dorsi flap, liposuction,
      abdominoplasty, and buttocks augmentation. Examples of complications, including
      seromas, abscesses, fat necrosis, abdominal hernia, and flap necrosis, will also
      be discussed.

PMID- 23174531
TI  - NIH TRND program: successes in preclinical therapeutic development.

PMID- 23174532
TI  - Beyond initial encoding: measures of the post-encoding status of memory traces
      predict long-term recall during infancy.
AB  - The first years of life are witness to rapid changes in long-term recall ability.
      In the current research we contributed to an explanation of the changes by
      testing the absolute and relative contributions to long-term recall of encoding
      and post-encoding processes. Using elicited imitation, we sampled the status of
      16-, 20-, and 24-month-old infants' memory representations at various time points
      after experience of events. In Experiment 1, infants were tested immediately, 1
      week after encoding, and again after 1 month. The measure of 1-week trace status
      was a unique predictor of 1-month delayed recall. In Experiment 2, infants were
      tested immediately, 15 min, 48 h, and 2 weeks after encoding and again 1 month
      later. The measures of 15-min and 48-h trace strength contributed unique variance
      in 1-month delayed recall. The findings highlight the need to consider post
      encoding processes in explanations of variability in long-term memory during
      infancy.

PMID- 23174533
TI  - In situ study of binding of copper by fulvic acid: comparison of differential
      absorbance data and model predictions.
AB  - This study examined the binding of copper(II) by Suwannee River fulvic acid
      (SRFA) using the method of differential absorbance that was used at
      environmentally-relevant concentrations of copper and SRFA. The pH- and metal
      differential spectra were processed via numeric deconvolution to establish
      commonalities seen in the changes of absorbance caused by deprotonation of SRFA
      and its interactions with copper(II) ions. Six Gaussian bands were determined to
      be present in both the pH- and Cu-differential spectra. Their maxima were
      located, in the order of increasing wavelengths at 208 nm, 242 nm, 276 nm, 314
      nm, 378 nm and 551 nm. The bands with these maxima were denoted as A0, A1, A2,
      A3, A4 and A5, respectively. Properties of these bands were compared with those
      existing in the spectra of model compounds such as sulfosalicylic acid (SSA),
      tannic acid (TA), and polystyrenesulfonic acid-co-maleic acid (PSMA). While none
      of the features observed in differential spectra of the model compound were
      identical to those present in the case of SRFA, Gaussian bands A1, A3 and
      possibly A2 were concluded to be largely attributable to a combination of
      responses of salicylic- and polyhydroxyphenolic groups. In contrast, bands A4 and
      A5 were detected in the differential spectra of SRFA only. Their nature remains
      to be elucidated. To examine correlations between the amount of copper(II) bound
      by SRFA and changes of its absorbance, differential absorbances measured at
      indicative wavelengths 250 nm and 400 nm were compared with the total amount of
      SRFA-bound copper estimated based on Visual MINTEQ calculations. This examination
      showed that the differential absorbances of SRFA in a wide range of pH values and
      copper concentrations were strongly correlated with the concentration of SRFA
      bound copper. The approach presented in this study can be used to generate in
      situ information concerning the nature of functional groups in humic substances
      engaged in interactions with metals ions. This information can be useful for
      further elaboration and development of detailed theoretic models that describe
      the complexation of metals in the environment.

PMID- 23174534
TI  - Effects of organic pollutants from wastewater treatment plants on aquatic
      invertebrate communities.
AB  - Pesticides are a major stressor for stream ecosystem health. They enter surface
      waters from diffuse agricultural sources but also from point sources such as
      municipal wastewater treatment plants (WWTPs). However, to date, no studies have
      focused on the ecological effects of pesticide-contaminated WWTP effluent on
      macroinvertebrate communities. On the basis of governmental monitoring data of
      328 sites in Hesse, Germany, we identified insecticidal long-term effects on the
      structure of the macroinvertebrate community up to 3 km downstream of WWTPs. The
      effects were quantified using the trait-based SPEAR(pesticides) index, which has
      been shown to be an effective tool for identifying community effects of pesticide
      contamination. In addition, based on the German Saprobic Index, we revealed that
      WWTPs are still an important source of oxygen-depleting organic pollution,
      despite the extensive technological improvements in wastewater management over
      several centuries. In general, our findings emphasize the need to take municipal
      WWTPs into consideration in the management of river basins under the EU Water
      Framework Directive to achieve good ecological and chemical status for European
      streams and rivers.

PMID- 23174535
TI  - Impact of treatment on Pb release from full and partially replaced harvested Lead
      Service Lines (LSLs).
AB  - Release of lead from 80% partially replaced service lines was compared to full
      lead service lines using harvested-stabilized lead pipes and field brass
      connectors. After more than a year of stabilization, lead release was consistent
      with field samples. Over the relatively short duration partial replacement of
      lead pipe by copper pipe (3 months), generated high lead release, attributed to
      galvanic corrosion, resulting in a final outcome for lead release that was even
      worse than for a full lead pipe. Increased lead release was especially evident at
      higher flow rates. Orthophosphate reduced lead release from full lead pipes by
      64%. For partially replaced samples with copper, lead concentrations were
      unchanged by phosphate dosing at moderate flow (103 +/- 265 vs 169 +/- 349 MUg/L)
      and were increased to very high levels when sampled at high flow rates (1001 +/-
      1808 vs 257 +/- 224 MUg/L). The increase lead release was in the form of
      particulate lead (>90%). In comparison to the condition without treatment,
      increased sulfate treatment had little impact on lead release from 100%-Pb rigs
      but reduced lead release from partially replaced lead pipes with copper. Our
      results also raise questions concerning protocols based on short 30 min
      stagnation (as those used in Canada) due to their incapacity to consider
      particulate lead release generated mostly after longer stagnation.

PMID- 23174536
TI  - MCM-48 modified magnetic mesoporous nanocomposite as an attractive adsorbent for
      the removal of sulfamethazine from water.
AB  - A novel magnetic mesoporous nanocomposite FeM48 was synthesized and applied to
      remove sulfamethazine (SMN) from water. The adsorption kinetics could be
      expressed by the pseudo-second-order model, where external and interfacial
      diffusions tended to be the rate-limiting step. The adsorption isotherms at
      varied temperatures were fitted well with Freundlich model, and thermodynamic
      analysis revealed that SMN adsorption on FeM48 was a spontaneous exothermic
      process. Solution pH exhibited a remarkable impact on the adsorption process and
      the maximum adsorbed concentration was obtained at pH 6.3. The effect of co
      existing anions and humic acid demonstrated that SMN could be adsorbed
      selectively by FeM48. Hydrogen bonding between the nitrogen of the aniline,
      sulfinol or pyrimidine group of SMN and the surface hydroxyl group of FeM48 was
      the major driving force for adsorption. In addition, the pi-pi electron-donor
      acceptor interaction between SMN (pi-electron-acceptor) and MCM-48 (pi-electron
      donor) also promoted the adsorption process.

PMID- 23174537
TI  - Involvement of Akt isoforms in chemoresistance of endometrial carcinoma cells.
AB  - OBJECTIVE: In tumors, upstream regulation of Akt is affected by oncogenic events
      which lead to its constitutive activation and promote cell survival. Since
      studies have demonstrated that the three Akt isoforms exhibit different
      physiological functions, Akt isoforms may contribute differently in
      chemoresistance. The objective of the study was to determine the role of each Akt
      isoforms in chemoresistance. METHODS: We stably transfected the chemoresistant
      KLE endometrial carcinoma cells with specific shRNAs for Akt1, Akt2 or Akt3.
      Alternatively, we stably transfected the chemosensitive Hec-1-A endometrial
      carcinoma cells, in which no Akt activity is detected, with constitutively active
      Akt expression vectors for each isoform. RESULTS: We demonstrated that Akt1 and
      Akt2 downregulation by RNAi highly sensitizes KLE cells to cisplatin by inducing
      the activation of pro-apoptotic factors such as the cleavage of caspases-3, -6, 
      9 and PARP; downregulation of all Akt isoforms leads to increased sensitivity to
      doxorubicin while only Akt1-2 downregulation increases taxol sensitivity.
      Proliferation of Akt1, and mostly Akt2 deficient cells was affected by cisplatin
      treatment. Constitutive Akt1 or Akt2 expression led to an increased resistance to
      apoptosis. Akt isoforms have been shown to influence migration in other cancer
      cells. We showed that Akt2 blocks cell motility, while Akt1-3 had less effect on
      our endometrial cancer cell models. CONCLUSION: Our findings highlight the
      contribution of Akt1 and Akt2 in the molecular mechanisms that govern
      chemoresistance of endometrial carcinomas. Furthermore, Akt isoform-specific
      transfectants will provide a strong model to determine the involvement of each
      Akt isoform in tumor progression and metastasis.

PMID- 23174538
TI  - Postoperative pelvic intensity-modulated radiotherapy in high risk endometrial
      cancer.
AB  - OBJECTIVE: According to national surveys, the use of intensity-modulated
      radiation therapy (IMRT) in gynecologic cancers is on the rise, yet there is
      still some reluctance to adopt adjuvant IMRT as standard practice. The purpose of
      this study is to report a single-institution experience using postoperative
      pelvic IMRT with or without chemotherapy in high-risk endometrial cancer.
      METHODS: From 11/2004 to 12/2009, 46 patients underwent hysterectomy/bilateral
      salpingo-oophorectomy for stage I-III (22% stage I/II and 78% stage III)
      endometrial cancer. Median IMRT dose was 50.4Gy. Adjuvant chemotherapy was given
      to 30 (65%) patients. RESULTS: With a median follow-up of 52months, 4 patients
      recurred: 1 vaginal plus lung metastasis, 2 isolated para-aortic recurrences, and
      1 lungs and liver metastasis. Five-year relapse rate was 9% (95% CI, 0-13.6%).
      Five-year disease-free survival (DFS) was 88% (95% CI, 77-98%) and overall
      survival (OS) was 97% (95% CI, 90-100%). There were 2 patients with non
      hematological grade 3 toxicity: 1 (2%) acute and 1 (2%) chronic gastrointestinal
      toxicity. In patients treated with IMRT and chemotherapy (n=30), 5 had grade 3
      leukopenia, 8 grade 2 anemia, and 2 grade 2 thrombocytopenia. CONCLUSIONS:
      Oncologic outcomes with postoperative IMRT were very good, with DFS and OS rates
      of >88% at median follow-up of 52months, despite a preponderance (78%) of stage
      III disease. Toxicity was minimal even in the setting of an aggressive
      trimodality (65% of patients) approach. Data from this study and emerging data
      from RTOG trial 0418 demonstrate the advantages of IMRT in high-risk endometrial
      cancer.

PMID- 23174539
TI  - Effects of early life permethrin exposure on spatial working memory and on
      monoamine levels in different brain areas of pre-senescent rats.
AB  - Pesticide exposure during brain development could represent an important risk
      factor for the onset of neurodegenerative diseases. Previous studies investigated
      the effect of permethrin (PERM) administered at 34 mg/kg, a dose close to the no
      observable adverse effect level (NOAEL) from post natal day (PND) 6 to PND 21 in
      rats. Despite the PERM dose did not elicited overt signs of toxicity (i.e. normal
      body weight gain curve), it was able to induce striatal neurodegeneration
      (dopamine and Nurr1 reduction, and lipid peroxidation increase). The present
      study was designed to characterize the cognitive deficits in the current animal
      model. When during late adulthood PERM treated rats were tested for spatial
      working memory performances in a T-maze-rewarded alternation task they took
      longer to choose for the correct arm in comparison to age matched controls. No
      differences between groups were found in anxiety-like state, locomotor activity,
      feeding behavior and spatial orientation task. Our findings showing a selective
      effect of PERM treatment on the T-maze task point to an involvement of frontal
      cortico-striatal circuitry rather than to a role for the hippocampus. The
      predominant disturbances concern the dopamine (DA) depletion in the striatum and,
      the serotonin (5-HT) and noradrenaline (NE) unbalance together with a
      hypometabolic state in the medial prefrontal cortex area. In the hippocampus, an
      increase of NE and a decrease of DA were observed in PERM treated rats as
      compared to controls. The concentration of the most representative marker for
      pyrethroid exposure (3-phenoxybenzoic acid) measured in the urine of rodents 12 h
      after the last treatment was 41.50 MUg/L and it was completely eliminated after
      96 h.

PMID- 23174540
TI  - Exercise and sports for health promotion, disease, and disability.

PMID- 23174541
TI  - Principles of exercise physiology: responses to acute exercise and long-term
      adaptations to training.
AB  - Physical activity and fitness are associated with a lower prevalence of chronic
      diseases, such as heart disease, cancer, high blood pressure, and diabetes. This
      review discusses the body's response to an acute bout of exercise and long-term
      physiological adaptations to exercise training with an emphasis on endurance
      exercise. An overview is provided of skeletal muscle actions, muscle fiber types,
      and the major metabolic pathways involved in energy production. The importance of
      adequate fluid intake during exercise sessions to prevent impairments induced by
      dehydration on endurance exercise, muscular power, and strength is discussed.
      Physiological adaptations that result from regular exercise training such as
      increases in cardiorespiratory capacity and strength are mentioned. The review
      emphasizes the cardiovascular and metabolic adaptations that lead to improvements
      in maximal oxygen capacity.

PMID- 23174542
TI  - Basic principles regarding strength, flexibility, and stability exercises.
AB  - Strength, flexibility, and stability are physiologic parameters associated with
      health-related physical fitness. Each of these domains affects health in general,
      the risk of injury, how an injury is treated, and performance in activities of
      daily living and sports. These domains are affected by individual phenotype, age,
      deconditioning, occupational activity, and formal exercise. Deficits or loss of
      strength, flexibility, and stability can be prevented or reduced with exercise
      programs. Normal muscle strength has been associated with general health
      benefits, increased life expectancy, psychological benefits, prevention of
      illness, and reduction of disability in older adults. Static flexibility programs
      have been shown to improve joint range of motion and tolerance to stretch but do
      not appear to reduce the risk of musculoskeletal injury and may impair muscle
      performance immediately after a static stretch. Dynamic flexibility, on the other
      hand, may enhance power and improve sports-specific performance. Stability
      training leads to improved balance and neuromuscular control, may prevent injury
      to the knee and ankle joints, and can be used for treatment of patients with low
      back pain.

PMID- 23174543
TI  - Psychosocial benefits and implications of exercise.
AB  - This review is based on a case report that concerns a young female athlete who
      experienced some of the negative aspects of exercise. Overtraining, a negative
      byproduct of excessive exercise, can turn the positive psychosocial and
      physiologic benefits of regular physical activity into an activity detrimental to
      one's health. With the proper psychological skills and appropriate exercise
      regimen, these negatives can be turned into positives. Once learned, the
      psychosocial benefits of exercise, as well as the positive implications, will
      become more prevalent, similar to the way in which proper physical training helps
      one become more fit over time.

PMID- 23174544
TI  - The exercise prescription: a tool to improve physical activity.
AB  - The current epidemic of sedentary behavior is a serious public health issue that
      requires the attention of the medical community. Although the benefits of
      physical activity are well established, research indicates that Americans are not
      heeding the message, and new strategies are warranted to bring about change in
      this arena. The health care community can and should play a key role in this
      movement. Patients respect their physicians as credible sources of information
      and look to them for health-related guidance. Unfortunately, many physicians are
      not talking to their patients about physical activity and are missing a unique
      opportunity to raise awareness about its benefits. Exercise needs to be discussed
      as a serious form of treatment, similar to medication, and should be thoughtfully
      prescribed to every patient. Physicians need to be familiar with the level of
      exercise necessary to achieve health benefits as defined by the Physical Activity
      Guidelines for Americans. Furthermore, they should be competent in their ability
      to identify a patient's level of risk for starting or increasing exercise and
      provide guidance on the frequency, intensity, time, and type of activity
      necessary to safely elicit maximal health benefits. These basic competencies can
      be easily understood by physicians and incorporated into their practices.
      Resources have been established to help support physicians in this process.
      Physiatrists are uniquely positioned to lead the effort for change in this area
      because they are well-established proponents of exercise and are trained to
      prescribe therapeutic exercise to address the complex medical issues of their
      patients. This skill-set should be used for every patient in an effort to reduce
      the widespread prevalence of the "chronic disease" physical inactivity.

PMID- 23174545
TI  - Physical activity in children and adolescents.
AB  - After obesity rates in youth reached alarming rates, public health officials
      recognized the need for specific physical activity guidelines for children and
      adolescents. Numerous health care groups and sports and fitness organizations
      collaborated on the development of the Physical Activity Guidelines for Americans
      in 2008, which have been widely endorsed and include recommendations for the
      pediatric population. Children and adolescents should participate in moderate-to
      vigorous physical activity 1 or more hours per day and muscle and bone
      strengthening activities 3 or more times per week. Physical activities should be
      age appropriate, enjoyable, and varied and occur beyond what is required for
      typical activities of daily living. Adequate exercise in youth improves strength,
      cardiorespiratory fitness, and body composition and therefore decreases
      cardiovascular risk factors. An improved cardiovascular profile provides a
      continued benefit in adulthood. Exercise also improves bone health, psychological
      well-being, cognition, and school performance and may decrease the risk of sports
      injury. Exercise habits established in childhood often continue into adulthood.

PMID- 23174546
TI  - Exercise in the older adult: from the sedentary elderly to the masters athlete.
AB  - The diverse exercise goals of the aging population present several challenges to
      physicians. Whereas some Masters athletes aim to set personal time records,
      sedentary elderly persons may look to exercise to help maintain independence and
      combat functional decline. This review article examines the common cardiovascular
      and neuromuscular physiological changes associated with aging and how regular
      exercise is used to improve physiological parameters and functional abilities.
      Exercise precautions specific to the elderly population are discussed. Exercise
      recommendations for persons with osteoarthritis and after joint arthroplasty also
      are presented.

PMID- 23174547
TI  - The role of exercise in the treatment of obesity.
AB  - The United States is in the midst of a significant public health problem that
      relates to obesity and inactivity. This epidemic has far-ranging consequences for
      our workforce and our children and shows no signs of slowing in the near future.
      Significant research has been performed on the effects of exercise for the
      reduction of body weight; results of most studies indicate that exercise alone
      has a small effect on body-weight reduction independent of caloric restriction.
      However, when combined with dietary restriction, exercise has a synergistic
      effect and enhances weight loss beyond the effect of diet alone. In addition,
      exercise has been shown to have significant beneficial effects on cardiovascular
      and metabolic risk factors independent of actual weight loss, and losing just a
      small amount of weight can have a significant beneficial effect on these
      parameters. Genetic factors related to obesity have been found to be positively
      modified when persons incorporate physical activity into their lifestyle. Sitting
      time appears to be an independent risk factor for the development of metabolic
      risk factors; persons who spend more time sitting and watching television have
      worse metabolic profiles, even if they achieve the recommended amount of physical
      activity per week, than do those who move about throughout the day. Exercise also
      is essential for the prevention of weight gain over a life span, although the
      amount required to prevent weight gain may be closer to twice the amount of
      exercise recommended by the current Physical Activity Guidelines for Americans
      (www.health.gov/paguidelines). In many ways, the physiatrist is the most well
      prepared of all the specialists to address the complex, multidimensional problems
      of obesity and inactivity.

PMID- 23174548
TI  - Benefits of exercise during pregnancy.
AB  - There is a direct link between healthy mothers and healthy infants. Exercise and
      appropriate nutrition are important contributors to maternal physical and
      psychological health. The benefits and potential risks of exercise during
      pregnancy have gained even more attention, with a number of studies having been
      published after the 2002 American College of Obstetrics and Gynecologists
      guidelines. A review of the literature was conducted by using PubMed, Scopus, and
      Embase to assess the literature regarding the benefits of exercise during
      pregnancy. The search revealed 219 publications, which the authors then narrowed
      to 125 publications. The purpose of this review is to briefly summarize the known
      benefits of exercise to the mother, fetus, and newborn.

PMID- 23174549
TI  - The Paralympic Movement: using sports to promote health, disability rights, and
      social integration for athletes with disabilities.
AB  - Competitive sports for people with disabilities has grown rapidly over the past
      several decades, and opportunities for participation are increasingly available
      throughout the spectrum from developmental to elite. The Paralympic Games, seen
      as the pinnacle sporting event that represents the broader Paralympic Movement,
      has provided a platform to showcase the abilities of people with disabilities
      while also serving as a catalyst for disability rights through ensuring
      integration, equality of opportunity, and accessibility of the built environment.
      Concurrently, media coverage of the Paralympic Games has led to an increased
      awareness of opportunities for sport participation for individuals with
      disabilities and, with it, the adjustment of norms regarding expectations for
      exercise as a component of preventive health. In addition, there is evidence of
      the power of sports to stimulate confidence, self-efficacy, and a self-perceived
      high quality of life for individuals with disabilities above and beyond the basic
      benefits to cardiometabolic fitness. When taken together, the promotion of
      health, disability rights, and social integration through sports has the power to
      transform the lives of those who participate and to further stimulate the
      expansion of opportunities available to the next generation of athletes with
      disabilities.

PMID- 23174550
TI  - Getting beyond the plateau: bridging the gap between rehabilitation and community
      based exercise.
AB  - Rehabilitation specialists have a unique opportunity to serve as the drivers of
      change in promoting the use of exercise facilities by people with newly acquired
      disabilities. Identifying programs that are effective and sustainable for
      extending recovery in a community-based exercise facility after rehabilitation
      may reduce the risk of secondary health complications and optimize health and
      function. This article describes an approach for closing the gap between
      inpatient and outpatient rehabilitation and the use of community-based exercise
      facilities by people with disabilities. Extending recovery from rehabilitation to
      community-based exercise requires a transitional setting (eg, hospital-based
      fitness facilities and specialized fitness centers and programs for people with
      disabilities) that provides greater support and supervision in teaching
      individuals with disabilities (and, when necessary, their caregivers) how to
      exercise safely and effectively and access the programs, equipment, and services
      available in these facilities. With the shortened amount of rehabilitation time
      that many patients are given after acquiring a disability or being treated for a
      new health condition, community-based exercise facilities and the fitness
      professionals who are employed in them must become part of the rehabilitation
      continuum and obtain additional training to better serve the needs of people with
      newly acquired disabilities who are leaving rehabilitation.

PMID- 23174551
TI  - Preventive exercise in sports.
AB  - Sports injuries are common and can result in significant problems, such as pain,
      social isolation, depression, disability (temporary or permanent), loss of
      income, or loss of scholarship. Further, sports injuries can predispose the
      athlete to future injury or degenerative disorders, for example, osteoarthritis.
      Therefore, a preventive approach is paramount, and exercise can be used as an
      effective tool to prevent sports-related injuries. This article describes the
      process by which successful injury prevention programs can be developed and
      implemented by using noncontact anterior cruciate ligament injury programs as an
      example. The knowledge gained from this information can be used in the future to
      assist in the creation of new injury prevention programs for other common sports
      injuries.

PMID- 23174553
TI  - The role and efficacy of exercise in persons with cancer.
AB  - Improvements in cancer screening, diagnosis, and treatment have resulted in an
      increasing population of cancer survivors with impairments in physical function,
      cancer-related symptoms, and reduced quality of life. Exercise and physical
      activity have therapeutic value at multiple points along the cancer disease
      continuum, spanning disease prevention, treatment, survivorship, prognostic
      outcomes, and end-of-life issues. Molecular mechanisms for the influence of
      exercise in persons with cancer include altering tumor initiation pathways and
      affecting hormonal, inflammatory, immune, and insulin pathways. Physical activity
      has been found to play a role in the prevention of certain malignancies,
      including breast, colon, and other cancers. An increasing amount of evidence
      indicates that physical activity may affect prognostic outcomes in certain cancer
      diagnoses, especially breast cancer. Structured exercise and physical activity
      interventions can be helpful in addressing specific survivorship issues,
      including overall quality of life, cardiorespiratory impairment, cancer-related
      fatigue, and lymphedema. Exercise also may be helpful during the palliative care
      phase to alleviate symptoms and increase physical well-being. This article will
      familiarize physiatrists with the current state of evidence regarding the role
      and efficacy of exercise in persons with cancer.

PMID- 23174552
TI  - Exercise in cardiovascular diseases.
AB  - Analysis of extensive data has shown that exercise training provides significant
      impact on prevention and modification of cardiovascular diseases and mortality.
      In general, exercise recommendations for patients with cardiovascular diseases
      are based on individual aerobic capacity and comorbidities. Patients with acute
      syndromes benefit from participating in a cardiac rehabilitation program, whereas
      patients with chronic syndromes benefit from a life-long home-based program. In
      general, exercise prescription should involve aerobic activities in combination
      with resistance, flexibility, and balance exercises. This review will discuss an
      exercise prescription for patients with coronary artery disease, heart failure,
      and after heart transplantation. Detailed precautions for particular groups of
      patients will be discussed.

PMID- 23174554
TI  - Exercise for patients with osteoporosis: management of vertebral compression
      fractures and trunk strengthening for fall prevention.
AB  - Maintenance of bone health and quality requires mechanical strain, but the
      mechanical force needs to be within the bone's biomechanical competence. In
      osteoporosis, compression of vertebral bodies can be insidious. Therefore,
      absence of pain does not necessarily indicate absence of vertebral microfracture
      and deformity. Further, patients with previous vertebral fractures are at risk
      for further vertebral fractures and their associated morbidity. Exercise is a
      part of the comprehensive management of patients with osteoporosis and has been
      associated with improvement of quality of life and lowered risk of future
      fracture. The exercise prescription needs to match the needs of the patient. If
      exercise is not prescribed properly, then it may have negative consequences. In
      general, an exercise program, therapeutic or recreational, needs to address
      flexibility, muscle strength, core stability, cardiovascular fitness, and gait
      steadiness. As with pharmacotherapy, therapeutic exercises need to be
      individualized on the basis of musculoskeletal status and an individual's
      exercise interest. In osteoporosis, axial strength and stability are of primary
      importance. In particular, a spinal extensor strengthening program should be
      performed with progressive measured resistance as tolerated. To address falls and
      fractures, an exercise program should also include balance and lower extremity
      strength training. Proper dosing of oral cholecalciferol and calcium supplements
      can enhance the effect of strengthening exercises. Finally, a coordinated
      approach, such as the Spinal Proprioception Extension Exercise Dynamic (SPEED)
      program, can improve back extensor strength, the level of physical activity, and
      locomotion, and reduce back pain and fear and risk of falls.

PMID- 23174555
TI  - Exercise in muscle pain disorders.
AB  - Muscle pain disorders range from local or regional (myofascial pain) to
      widespread (fibromyalgia). Many people with muscle pain have decreased fitness.
      Exercise intolerance is a common feature as well, and yet exercise plays an
      important role in the treatment of muscle pain disorders. Results of studies have
      shown repeatedly, via multiple modes and methods of delivery, that exercise is at
      least as effective as the best pharmacologic treatments. An understanding by
      clinicians and their patients of the unique benefits of a carefully crafted
      exercise program is one step in the successful management of these often
      frustrating muscle pain disorders.

PMID- 23174556
TI  - Exercise and sport for persons with spinal cord injury.
AB  - This review article provides an overview of the evidence that links exercise and
      sports participation to physical and psychological well-being among people with
      spinal cord injury. Two aspects of physical well-being are examined, including
      the prevention of chronic disease and the promotion of physical fitness. Multiple
      aspects of psychosocial well-being are discussed, including mental health, social
      participation, and life satisfaction. The review concludes with future research
      recommendations and a discussion of challenges and opportunities for using
      exercise and sports to promote health and well-being among people living with
      spinal cord injury.

PMID- 23174557
TI  - Effects of cardiorespiratory fitness and muscle-resistance training after stroke.
AB  - Stroke is a leading cause of long-term disability. The physical and cognitive
      impairments after an ischemic or hemorrhagic stroke often lead to activity
      limitations and participation restrictions. Many persons after stroke have a
      sedentary lifestyle, are physically inactive, and have a low fitness level.
      Physical fitness training is known to be beneficial for persons with a number of
      comorbid conditions or risk factors for stroke. Although exercise and physical
      activity are considered valuable, the evidence of their benefits after stroke is
      still insufficient. In this review, we summarize published randomized controlled
      trials regarding the effects of cardiorespiratory fitness and muscle-resistance
      training after stroke on physical function, activity, participation, life
      satisfaction, and mood. We discuss various barriers that can impede the ability
      to perform exercise, and the importance of reducing these barriers to increase
      physical fitness levels after the completion of usual stroke rehabilitation,
      thereby enhancing leisure, well-being, and participation in society.

PMID- 23174558
TI  - Exercise to enhance neurocognitive function after traumatic brain injury.
AB  - Vigorous exercise has long been associated with improved health in many domains.
      Results of clinical observation have suggested that neurocognitive performance
      also is improved by vigorous exercise. Data derived from animal model-based
      research have been emerging that show molecular and neuroanatomic mechanisms that
      may explain how exercise improves cognition, particularly after traumatic brain
      injury. This article will summarize the current state of the basic science and
      clinical literature regarding exercise as an intervention, both independently and
      in conjunction with other modalities, for brain injury rehabilitation. A key
      principle is the factor of timing of the initiation of exercise after mild
      traumatic brain injury, balancing potentially favorable and detrimental effects
      on recovery.

PMID- 23174559
TI  - A call to arms (and legs): exercise prescription for medical students.

PMID- 23174560
TI  - Osteochondral tissue engineering: current strategies and challenges.
AB  - Osteochondral defect management and repair remain a significant challenge in
      orthopedic surgery. Osteochondral defects contain damage to both the articular
      cartilage as well as the underlying subchondral bone. In order to repair an
      osteochondral defect the needs of the bone, cartilage and the bone-cartilage
      interface must be taken into account. Current clinical treatments for the repair
      of osteochondral defects have only been palliative, not curative. Tissue
      engineering has emerged as a potential alternative as it can be effectively used
      to regenerate bone, cartilage and the bone-cartilage interface. Several scaffold
      strategies, such as single phase, layered, and recently graded structures have
      been developed and evaluated for osteochondral defect repair. Also, as a
      potential cell source, tissue specific cells and progenitor cells are widely
      studied in cell culture models, as well with the osteochondral scaffolds in vitro
      and in vivo. Novel factor strategies being developed, including single factor,
      multi-factor, or controlled factor release in a graded fashion, not only assist
      bone and cartilage regeneration, but also establish osteochondral interface
      formation. The field of tissue engineering has made great strides, however
      further research needs to be carried out to make this strategy a clinical
      reality. In this review, we summarize current tissue engineering strategies,
      including scaffold design, bioreactor use, as well as cell and factor based
      approaches and recent developments for osteochondral defect repair. In addition,
      we discuss various challenges that need to be addressed in years to come. 

PMID- 23174561
TI  - Methane biogenesis during sodium azide-induced chemical hypoxia in rats.
AB  - Previous studies demonstrated methane generation in aerobic cells. Our aims were
      to investigate the methanogenic features of sodium azide (NaN(3))-induced
      chemical hypoxia in the whole animal and to study the effects of l-alpha
      glycerylphosphorylcholine (GPC) on endogenous methane production and inflammatory
      events as indicators of a NaN(3)-elicited mitochondrial dysfunction. Group 1 of
      Sprague-Dawley rats served as the sham-operated control; in group 2, the animals
      were treated with NaN(3) (14 mg.kg(-1).day(-1) sc) for 8 days. In group 3, the
      chronic NaN(3) administration was supplemented with daily oral GPC treatment.
      Group 4 served as an oral antibiotic-treated control (rifaximin, 10 mg.kg(
      1).day(-1)) targeting the intestinal bacterial flora, while group 5 received this
      antibiotic in parallel with NaN(3) treatment. The whole body methane production
      of the rats was measured by means of a newly developed method based on
      photoacoustic spectroscopy, the microcirculation of the liver was observed by
      intravital videomicroscopy, and structural changes were assessed via in vivo
      fluorescent confocal laser-scanning microscopy. NaN(3) administration induced a
      significant inflammatory reaction and methane generation independently of the
      methanogenic flora. After 8 days, the hepatic microcirculation was disturbed and
      the ATP content was decreased, without major structural damage. Methane
      generation, the hepatic microcirculatory changes, and the increased tissue
      myeloperoxidase and xanthine oxidoreductase activities were reduced by GPC
      treatment. In conclusion, the results suggest that methane production in mammals
      is connected with hypoxic events associated with a mitochondrial dysfunction. GPC
      is protective against the inflammatory consequences of a hypoxic reaction that
      might involve cellular or mitochondrial methane generation.

PMID- 23174563
TI  - Ouabain downregulates Mcl-1 and sensitizes lung cancer cells to TRAIL-induced
      apoptosis.
AB  - Resistance to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is
      a prerequisite for cancer progression, and TRAIL resistance is prevalent in lung
      cancer. Ouabain, a recently identified human hormone, has shown therapeutic
      promise by potentiating the apoptotic response of metastatic lung cancer cells to
      TRAIL. Nontoxic concentrations of ouabain are shown to increase caspase-3
      activation, poly(ADP-ribose) polymerase (PARP) cleavage, and apoptosis of H292
      cells in response to TRAIL. While ouabain had a minimal effect on c-FLIP, Bcl-2,
      and Bax levels, we show that it possesses an ability to downregulate the
      antiapoptotic Mcl-1 protein. The present study also reveals that the sensitizing
      effect of ouabain is associated with its ability to generate reactive oxygen
      species (ROS), and hydrogen peroxide is identified as the principle ROS
      triggering proteasomal Mcl-1 degradation. In summary, our results indicate a
      novel function for ouabain in TRAIL-mediated cancer cell death through Mcl-1
      downregulation, thereby providing new insight into a potential lung cancer
      treatment as well as a better understanding of the physiological activity of
      ouabain.

PMID- 23174562
TI  - Mis-expression of the BK K(+) channel disrupts suprachiasmatic nucleus circuit
      rhythmicity and alters clock-controlled behavior.
AB  - In mammals, almost all aspects of circadian rhythmicity are attributed to
      activity in a discrete neural circuit of the hypothalamus, the suprachiasmatic
      nucleus (SCN). A 24-h rhythm in spontaneous firing is the fundamental neural
      intermediary to circadian behavior, but the ionic mechanisms that pattern circuit
      rhythmicity, and the integrated impact on behavior, are not well studied. Here,
      we demonstrate that daily modulation of a major component of the nighttime-phased
      suppressive K(+) current, encoded by the BK Ca(2+)-activated K(+) current channel
      (K(Ca)1.1 or Kcnma1), is a critical arbiter of circadian rhythmicity in the SCN
      circuit. Aberrant induction of BK current during the day in transgenic mice using
      a Per1 promoter (Tg-BK(R207Q)) reduced SCN firing or silenced neurons, decreasing
      the circadian amplitude of the ensemble circuit rhythm. Changes in cellular and
      circuit excitability in Tg-BK(R207Q) SCNs were correlated with elongated
      behavioral active periods and enhanced responses to phase-shifting stimuli.
      Unexpectedly, despite the severe reduction in circuit amplitude, circadian
      behavioral amplitudes in Tg-BK(R207Q) mice were relatively normal. These data
      demonstrate that downregulation of the BK current during the day is essential for
      the high amplitude neural activity pattern in the SCN that restricts locomotor
      activity to the appropriate phase and maintains the clock's robustness against
      perturbation. However, a residually rhythmic subset prevails over the ensemble
      circuit to drive the fundamental circadian behavioral rhythm.

PMID- 23174564
TI  - Cellular mechanisms of tissue fibrosis. 2. Contributory pathways leading to
      myocardial fibrosis: moving beyond collagen expression.
AB  - While the term "fibrosis" can be misleading in terms of the complex patterns and
      processes of myocardial extracellular matrix (ECM) remodeling, fibrillar collagen
      accumulation is a common consequence of relevant pathophysiological stimuli, such
      as pressure overload (PO) and myocardial infarction (MI). Fibrillar collagen
      accumulation in both PO and MI is predicated on a number of diverse cellular and
      extracellular events, which include changes in fibroblast phenotype
      (transdifferentiation), posttranslational processing and assembly, and finally,
      degradation. The expansion of a population of transformed
      fibroblasts/myofibroblasts is a significant cellular event with respect to ECM
      remodeling in both PO and MI. The concept that this cellular expansion within the
      myocardial ECM may be due, at least in part, to endothelial-mesenchymal
      transformation and thereby not dissimilar to events observed in cancer
      progression holds intriguing future possibilities. Studies regarding determinants
      of procollagen processing, such as procollagen C-endopeptidase enhancer (PCOLCE),
      and collagen assembly, such as the secreted protein acidic and rich in cysteine
      (SPARC), have identified potential new targets for modifying the fibrotic
      response in both PO and MI. Finally, the transmembrane matrix metalloproteinases,
      such as MMP-14, underscore the diversity and complexity of this ECM proteolytic
      family as this protease can degrade the ECM as well as induce a profibrotic
      response. The growing recognition that the myocardial ECM is a dynamic entity
      containing a diversity of matricellular and nonstructural proteins as well as
      proteases and that the fibrillar collagens can change in structure and content in
      a rapid temporal fashion has opened up new avenues for modulating what was once
      considered an irreversible event--myocardial fibrosis.

PMID- 23174565
TI  - Copper stabilizes the Menkes copper-transporting ATPase (Atp7a) protein expressed
      in rat intestinal epithelial cells.
AB  - Iron deficiency decreases oxygen tension in the intestinal mucosa, leading to
      stabilization of hypoxia-inducible transcription factor 2alpha (Hif2alpha) and
      subsequent upregulation of genes involved in iron transport [e.g., divalent metal
      transporter (Dmt1) and ferroportin 1 (Fpn1)]. Iron deprivation also alters copper
      homeostasis, reflected by copper accumulation in the intestinal epithelium and
      induction of an intracellular copper-binding protein [metallothionein (Mt)] and a
      copper exporter [Menkes copper ATPase (Atp7a)]. Importantly, Atp7a is also a
      Hif2alpha target. It was, however, previously noted that Atp7a protein expression
      was induced more strongly than mRNA in the duodenum of iron-deprived rats,
      suggesting additional regulatory mechanisms. The current study was thus designed
      to decipher mechanistic aspects of Atp7a regulation during iron deprivation using
      an established in vitro model of the mammalian intestine, rat intestinal
      epithelial (IEC-6) cells. Cells were treated with an iron chelator and/or copper
      loaded to mimic the in vivo situation. IEC-6 cells exposed to copper showed a
      dose-dependent increase in Mt expression, confirming intracellular copper
      accumulation. Iron chelation with copper loading increased Atp7a mRNA and protein
      levels; however, contrary to our expectation, copper alone increased only protein
      levels. This suggested that copper increased Atp7a protein levels by a
      posttranscriptional regulatory mechanism. Therefore, to determine if Atp7a
      protein stability was affected, the translation inhibitor cycloheximide was
      utilized. Experiments in IEC-6 cells revealed that the half-life of the Atp7a
      protein was ~41 h and, furthermore, that intracellular copper accumulation
      increased steady-state Atp7a protein levels. This investigation thus reveals a
      novel mechanism of Atp7a regulation in which copper stabilizes the protein,
      possibly complementing Hif2alpha-mediated transcriptional induction during iron
      deficiency.

PMID- 23174567
TI  - Comparative utility of the BESTest, mini-BESTest, and brief-BESTest for
      predicting falls in individuals with Parkinson disease: a cohort study.
AB  - BACKGROUND: The newly developed brief-balance evaluation system test (brief
      BESTest) may be useful for measuring balance and predicting falls in individuals
      with Parkinson disease (PD). OBJECTIVES: The purposes of this study were: (1) to
      describe the balance performance of those with PD using the brief-BESTest, (2) to
      determine the relationships among the scores derived from the 3 versions of the
      BESTest (i.e., full BESTest, mini-BESTest, and brief-BESTest), and (3) to compare
      the accuracy of the brief-BESTest with that of the mini-BESTest and BESTest in
      identifying recurrent fallers among people with PD. DESIGN: This was a
      prospective cohort study. METHODS: Eighty participants with PD completed a
      baseline balance assessment. All participants reported a fall history during the
      previous 6 months. Fall history was again collected 6 months (n=51) and 12 months
      (n=40) later. RESULTS: At baseline, participants had varying levels of balance
      impairment, and brief-BESTest scores were significantly correlated with mini
      BESTest (r=.94, P<.001) and BESTest (r=.95, P<.001) scores. Six-month
      retrospective fall prediction accuracy of the Brief-BESTest was moderately high
      (area under the curve [AUC]=0.82, sensitivity=0.76, and specificity=0.84).
      Prospective fall prediction accuracy over 6 months was similarly accurate
      (AUC=0.88, sensitivity=0.71, and specificity=0.87), but was less sensitive over
      12 months (AUC=0.76, sensitivity=0.53, and specificity=0.93). LIMITATIONS: The
      sample included primarily individuals with mild to moderate PD. Also, there was a
      moderate dropout rate at 6 and 12 months. CONCLUSIONS: All versions of the
      BESTest were reasonably accurate in identifying future recurrent fallers,
      especially during the 6 months following assessment. Clinicians can reasonably
      rely on the brief-BESTest for predicting falls, particularly when time and
      equipment constraints are of concern.

PMID- 23174568
TI  - Pemphigoid with autoantibodies to all laminin 332 subunits and BP230 developing
      vesicles within psoriatic plaques.

PMID- 23174566
TI  - Exogenous modification of platelet membranes with the omega-3 fatty acids EPA and
      DHA reduces platelet procoagulant activity and thrombus formation.
AB  - Several studies have implicated the omega-3 fatty acids eicosapentaenoic acid
      (EPA) and docosahexaenoic acid (DHA) in inhibition of normal platelet function,
      suggesting a role for platelets in EPA- and DHA-mediated cardioprotection.
      However, it is unclear whether the cardioprotective mechanisms arise from
      alterations to platelet-platelet, platelet-matrix, or platelet-coagulation factor
      interactions. Our previous results led us to hypothesize that EPA and DHA alter
      the ability of platelets to catalyze the generation of thrombin. We tested this
      hypothesis by exogenously modifying platelet membranes with EPA and DHA, which
      resulted in compositional changes analogous to increased dietary EPA and DHA
      intake. Platelets treated with EPA and DHA showed reductions in the rate of
      thrombin generation and exposure of platelet phosphatidylserine. In addition,
      treatment of platelets with EPA and DHA decreased thrombus formation and altered
      the processing of thrombin precursor proteins. Furthermore, treatment of whole
      blood with EPA and DHA resulted in increased occlusion time and a sharply reduced
      accumulation of fibrin under flow conditions. These results demonstrate that EPA
      and DHA inhibit, but do not eliminate, the ability of platelets to catalyze
      thrombin generation in vitro. The ability of EPA and DHA to reduce the
      procoagulant function of platelets provides a possible mechanism behind the
      cardioprotective phenotype in individuals consuming high levels of EPA and DHA.

PMID- 23174569
TI  - [Expressions of adiponectin and its receptors in the retina of normal and type 1
      diabetic mice].
AB  - OBJECTIVE: To investigate the expression of adiponectin and its receptors
      (AdipoRs) in the retina of normal mice and mice with type 1 diabetes mellitus
      (T1DM). METHODS: C57BL/6 mice were randomly divided into control group and
      streptozotocin-induced T1DM group. Two months after the modeling, the total
      protein and adiponectin protein expression in the retina and choroid were
      measured using BCA method and enzyme-linked immunosorbent assay, respectively.
      Quantitative RT-PCR was performed to detect the mRNA expressions of AdipoRs in
      the retina and choroid, and Western blotting was employed to examine the protein
      expressions of AdipoRs in the retina. RESULTS: Adiponectin and AdipoRs proteins
      were expressed in the retina and choroid in normal mice. The expressions of
      adiponectin and AdipoR1 were up-regulated in the retina of mice with T1DM while
      AdipoR2 expression exhibited no significant changes. CONCLUSION: Adiponectin and
      AdipoR1 may play an important role in the evolvement of type 1 diabetic
      retinopathy.

PMID- 23174570
TI  - [Effect of low-molecular-weight heparin combined with paclitaxel on the
      invasiveness and migration of nasopharyngeal carcinoma cells in vitro].
AB  - OBJECTIVE: To investigate the effect of low-molecular-weight heparin (LMWH)
      combined with paclitaxel (PTX) on the invasiveness and migration of
      nasopharyngeal carcinoma cells and explore the molecular mechanisms. METHODS: MTT
      assay was used to detect the growth inhibition induced by LMWH and PTX in CNE1
      and CNE2 cells. Wound healing assay and Transwell migration assay were employed
      to assess the effects of the drugs on the cell migration, and Transwell invasion
      assay was used to evaluate the cell invasiveness. The cellular expression of
      matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of matrix
      metalloproteinase-1 (TIMP-1) were analyzed by Western blotting. ELISA was used to
      determine the expression of heparanase (HPA) in the culture medium of the cells.
      RESULTS: MTT assay showed an obvious suppression of CNE1 and CNE2 cell
      proliferation in response to LMWH and PTX treatments. Treatment with 200 U.ml
      LMWH combined with 0.1 umol.L PTX for 24 h resulted in the inhibition rates of
      migration of 66.70% and 70.53% in CNE1 and CNE2 cells, respectively significantly
      higher than the rates in cells with PTX treatment alone. The combined treatment
      with LMWH and PTX for 24 h also caused a significantly higher inhibition rate of
      cell invasion than LMWH and PTX alone. LMWH enhanced the down-regulation of MMP-9
      and HPA induced by PTX. CONCLUSION: LMWH can enhance the inhibitory effect of PTX
      on the migration and invasion of nasopharyngeal carcinoma cells, the mechanism of
      which may involve the down-regulation of MMP-9 and HPA expressions.

PMID- 23174571
TI  - [Effects of seven RNA silencing suppressors on heterologous expression of green
      fluorescence protein expression mediated by a plant virus-based system in
      Nicotiana benthamiana].
AB  - OBJECTIVE: To test the effects of 7 virus-encoded RNA silencing suppressors
      (RSSs) for enhancement of a plant virus-based vector system-mediated heterologous
      expression of green fluorescence protein (GFP) in Nicotiana benthamiana. METHODS:
      Seven transient expression vectors for the 7 RSSs were constructed and co
      inoculated on the leaves of Nicotiana benthamiana with PVXdt-GFP vector, a novel
      Potato virus X-based plant expression vector, through agroinfiltration. The
      protein and mRNA expression levels of the reporter gene GFP in the co-inoculated
      Nicotiana leaves were examined by Western blotting, ELISA and RT-qPCR to assess
      the effect of the RSSs for GFP expression enhancement. RESULTS: The 7 RSSs
      differed in the degree and duration of enhancement of heterologous GFP
      expression, and the p19 protein of Tomato bushy stunt virus (TBSV) induced the
      highest expression of GFP. African cassava mosaic virus AC2 protein and Rice
      yellow mettle virus P1 protein produced no obvious enhancement GFP expression.
      CONCLUSION: Transient co-expression of RSSs suppresses host silencing response to
      allow high-level and long-term expression of heterologous genes in plant, but the
      optimal RSS has to be identified for each plant virus-based expression vector
      system.

PMID- 23174572
TI  - [Annexin A2 expression in intestinal mucosa of patients with inflammatory bowel
      disease and its clinical implications].
AB  - OBJECTIVE: To explore the role of annexin A2 (ANXA2) expression in the intestinal
      mucosa in the pathogenesis of inflammatory bowel disease (IBD). METHODS:
      Intestinal or colonic mucosal biopsy samples were obtained from 54 patients with
      ulcerative colitis (UC), 37 with Crohn's disease (CD), and 15 healthy control
      subjects. Immunohistochemistry was employed to examine the expression of ANXA2 in
      the intestinal mucosa, and mRNA expression of ANXA2 was detected using real-time
      PCR. RESULTS: Immunohistochemistry showed a ANXA2 positivity rate of 83.3%
      (45/54) in patients with UC, 27.0% (10/37) in patients with CD, and 53.3% (8/15)
      in the control subjects. ANXA2 expression in the intestinal or colonic mucosa was
      significantly up-regulated in patients with UC compared with the patients with CD
      and healthy control subjects, but was significantly lower in patients with CD
      than in the healthy controls (P<0.05). The expression levels of ANXA2 were
      strongly associated with the severity of clinical manifestations and the
      histopathological grades of UC (P<0.05). Compared with the healthy controls and
      patients with CD, patients with UC showed a significantly increased ANXA2 mRNA
      expression level in the inflamed mucosa of UC (P<0.05). CONCLUSION: ANXA2 can
      serve as a marker for differential diagnosis of IBD, and its up-regulated
      expression is closely related to the pathogenesis of UC.

PMID- 23174573
TI  - [Analysis of angiogenesis and lymphangiogenesis signaling pathways based on gene
      expression patterns of nasopharyngeal carcinoma].
AB  - OBJECTIVE: To pinpoint angiogenesis- and lymphangiogenesis-related genes in
      nasopharyngeal carcinoma (NPC). METHODS: Based on the reported microarray data
      which identified 831 differentially expressed genes in NPC tissues and the latest
      genomic information, we selected 246 genes for analysis with the smallest
      differential expression threshold of 260. Gene function analysis and network
      construction was carried out based on literature mining for analysis of the
      signaling pathways related with angiogenesis and lymphangiogenesis of NPC.
      RESULTS: The 246 genes were related with such keywords as nasopharyngeal
      carcinoma, EB virus, metastasis, angiogenesis, lymphangiogenesis, and invasion.
      Particularly, we found that up to 52 genes were associated with angiogenesis
      (P=0.00001), and 19 genes form 12 related gene pairs (P=0.0042). Twenty-one
      lymphangiogenesis-related genes were identified (P=0.00001), and 6 of these genes
      formed a gene network (P=0.0226). Eight genes, including PTGS2, participated in
      the nuclear factor-kappaB (NF-kappaB) pathway, which was closely related to
      angiogenesis in small cell lung cancer (P=7.87E-07). Five genes, including STAT1
      and CXCL10, participated in toll-like receptor signaling pathway (P=0.00176).
      CONCLUSION: PTGS2 and NF-kappaB promote angiogenesis of NPC, and the role of toll
      like receptor signaling pathway in lymphangiogenesis warrants further
      investigation.

PMID- 23174574
TI  - [Down-regulation of miR-21 expression enhances the radiosensitivity of TE-1 cells
      in vitro].
AB  - OBJECTIVE: To study the effect of miR-21 down-regulation on the radiosensitivity
      of TE-1 cells in vitro. METHODS: TE-1 cells were transfected via lentivirus with
      a vector containing the antisense oligonucleotides of miR21, and the subclones
      with stable down-regulation of miR21 expression were selected with puromycin and
      designated as TE-1-miR21(-), whose expression level of miR21 was determined using
      real-time quantitative PCR. The radiosensitivity of TE-1 and TE-1-miR21(-) cells
      were evaluated with colony formation assay, and the expressions of beta-catenin
      was determined using Western blotting and RT-PCR. Flow cytometry was used to
      analyze the proportion of p75NTR(+) cells in TE-1 and TE-1-miR21(-) cells.
      RESULTS: A cell subclone stably expressing a low level of miR21 was obtained and
      verified by real-time quantitative PCR. Colony formation assay showed an enhanced
      the radiosensitivity of TE-1-miR21(-) cells compared to parental TE-1 cells. RT
      PCR revealed no significant changes in beta-catenin mRNA expression in TE-1
      miR21(-) cells, whereas its beta-catenin protein expression was markedly
      suppressed by high-dose (8 and 10 Gy) irradiation. Flow cytometry assay showed a
      decreased proportion of p75NTR(+) cells in TE-1-miR21(-) cells compared to that
      in TE-1 cells. CONCLUSION: Down-regulation of miR21 can enhance the
      radiosensitivity of TE-1 cells, which might result from the inactivation of
      wnt/beta-catenin signal pathway and a decreased p75NTR(+) cell proportion.

PMID- 23174575
TI  - [Establishment of an isolated porcine liver machine perfusion model for high
      intensity focused ultrasound studies].
AB  - OBJECTIVE: To explore the feasibility of establishing an isolated porcine liver
      machine perfusion model and assess its value in high-intensity focused ultrasound
      studies. METHODS: Twenty-one isolated porcine livers were perfused with
      autologous blood for 4 h through dual vessels (portal vein and hepatic artery)
      cannulation using an extracorporeal circulation machine under a sub-normothermic
      perfusion condition. The perfusion model was assessed by monitoring the liver
      color, texture, liver weight gain, hemodynamic parameters, color Doppler flow
      imaging, bile output and histopathology. RESULTS: Nineteen isolated porcine
      livers were successfully cannulated with dual vessels, and failure of hepatic
      artery intubation occurred in two porcine livers. After machine perfusion for 4
      h, the isolated livers maintained a soft texture with stable hemodynamic levels
      within relative normal physiological ranges. The bile output was more than 3 ml/h
      within the initial 3 h of perfusion. Histopathological examination demonstrated
      no morphological or structural changes of the liver tissues. CONCLUSION: The
      isolated porcine liver perfusion model is stable and feasible, and can be used
      for high-intensity focused ultrasound studies.

PMID- 23174576
TI  - [Association of miR-199a expression with clinicopathologic characteristics and
      prognosis of renal cell carcinoma].
AB  - OBJECTIVE: To investigate the association of miR-199a expression with the
      clinicopathologic characteristics and the survival of patients with renal cell
      carcinoma (RCC). METHODS: Real-time quantitative RT-PCR was used to detect the
      expression of miR-199a in the tumor tissues and paired adjacent normal tissues
      from 67 patients with RCC. The correlations of miR-199a expression with the
      clinicopathologic characteristics and survival of RCC patients were analyzed.
      RESULTS: Positive miR-199a expression was detected in both the RCC and adjacent
      normal tissues, but the tumor tissues showed a significantly lower expression
      level by a mean of 13.7 folds (P=0.003). The expression of miR-199a was
      negatively correlated with tumor recurrence in RCC patients in T stage (P<0.05),
      but showed no significant correlations with the patients age, histological type
      of the tumor, lymph node metastasis, distal metastasis, or Fuhrman grade
      (P>0.05). The patients with lowered miR-199a expression in the tumor tissue had a
      significantly shorter mean survival time than those without miR-199a down
      regulation (P=0.017 by Log-rank test). CONCLUSION: A decreased expression of miR
      199a is significantly correlated with a higher tumor stage, a greater likeliness
      of tumor recurrence, and a poorer prognosis in RCC patients. miR-199a can serve
      as a promising prognostic factor of renal cell carcinoma.

PMID- 23174577
TI  - [Cytoplasmic expression of CDK4 protein and its correlation with the
      clinicopathologic features and prognosis of lung cancer].
AB  - OBJECTIVE: To evaluate the correlation of CDK4 protein expression in the
      cytoplasm with the clinicopathologic features and prognosis of lung cancer.
      METHODS: Immunohistochemistry was employed to examine CDK4 protein expression in
      the cytoplasm of lung cancer samples, using normal lung tissue samples as
      control. The correlation of cytoplasmic CDK4 protein expression with the
      clinicopathologic parameters and prognosis of lung cancer patients was analyzed.
      RESULTS: No significant difference was found in cytoplasmic CDK4 protein
      expression levels between lung cancer and normal lung tissues (P=1.000). In the
      lung cancer tissues, however, an increased cytoplasmic expression of CDK4 was
      positively correlated with the clinical stages and lymph node metastasis.
      Prognostic analysis showed that the patients with an increased cytoplasmic CDK4
      expression had a markedly shorter overall survival than those with a low
      cytoplasmic CDK4 expression. Multivariate analysis suggested that the level of
      cytoplasmic CDK4 expression was an independent prognostic indicator for the
      survival of patients with lung cancer (P<0.001). CONCLUSION: Overexpression of
      CDK4 protein in the cytoplasm may promote the carcinogenesis of lung cancer and
      can be an unfavorable prognostic factor for the survival of lung cancer patients.

PMID- 23174578
TI  - [Retrograde changes in the dorsal motor nuclei of rat vagus nerve after
      vagotomy].
AB  - OBJECTIVE: To investigate the retrograde changes in the dorsal motor nuclei (DMV)
      of the vagus nerve after vagotomy in rats. METHODS: Nissl staining and
      immunohistochemistry were used to observe the morphological and quantitative
      changes of the DMV and alterations of the expression of iNOS and NADPH after
      severing of the vagus nerve in adult male Wistar rats. RESULTS: Compared with the
      control group, the rats with right vagotomy showed obvious morphological changes
      and a significantly decreased number of neurons in the right DMV (P<0.05).
      Numerous iNOS- and NADPH-immunopositive cells were detected in the right DMV 5
      and 10 days after right vagotomy. CONCLUSION: Vagotomy causes obvious retrograde
      changes in rat DMV shown by a significantly decreased number and obvious
      morphological changes of the neurons in the DMV.

PMID- 23174579
TI  - [Protective effect of amlodipine against contrast agent-induced renal injury in
      elderly patients with coronary heart disease].
AB  - OBJECTIVE: To evaluate the protective effect of amlodipine against contrast agent
      induced renal injury in elderly patients with coronary heart disease. METHODS: A
      total of 189 elderly patients (>60 years) with coronary heart disease undergoing
      coronary artery angiography were randomly assigned into amlodipine group and
      control group to receive amlodipine or placebo, respectively, before and after
      administration of the contrast agent. At 24 h, 48 h and 5 days after contrast
      agent administration, the parameters of renal function were measured including
      serum cystatin C, urea nitrogen, creatinine, creatinine clearance rate, urine
      beta2-microglobulin, and urine N-acetyl-beta-glucosaminidase. RESULTS: In both
      groups, the contrast agents obviously affected the renal functions  of the
      patients (P<0.05). At 24 h after contrast administration, the levels of serum
      cystatin C, urine beta2-microglobulin and urine NAG were significantly lower in
      amlodipine group than in the control group, but the other functional parameters
      showed no significant difference. At 48 h after contrast administration, the
      glomerular and tubular functional parameters were all superior in amlodipine
      group (P<0.05). At 5 days, the two groups showed significant differences in such
      glomerular and tubular functional parameters as urea nitrogen, creatinine,
      creatinine clearance rate, urine beta2-microglobulin, and urine NAG (P<0.05), but
      not in serum cystatin C level. The incidence of contrast agent-induced
      nephropathy was significantly lower in amlodipine group than in the control group
      (5/95 vs 10/94, P<0.05). CONCLUSIONS: Amlodipine offers protection against
      radiographic contrast agent-induced renal injury in elderly patients with
      coronary heart disease.

PMID- 23174580
TI  - [Preparation of the trimeric subunits of recombinant human mannan-binding lectin
      and analysis of its bioactivity].
AB  - OBJECTIVE: To prepare the trimeric subunits of recombinant human mannan-binding
      lectin (MBL) with biological activities. METHODS: A prokaryotic expression vector
      containing human MBL N-terminal deletant (rhMBLdeltaN) gene we previously
      constructed was transformed into E. coli for efficient expression of rhMBLdeltaN
      fusion protein. Based on the principle that the collagen polypeptides tend to
      self-assembly into the tertiary structure of proteins by forming a triple helix
      due to the characteristic properties of the collagen proteins, rhMBLdeltaN fusion
      protein was limitedly hydrolyzed with thrombin. The obtained rhMBLdeltaN
      polypeptide was repeatedly dialyzed in 50 mmol/L PBS (pH7.2) and ddH(2)O, and the
      final product was analyzed for its bioactivities using a ligand-binding assay and
      a C4d deposition assay. RESULTS: rhMBLdeltaN polypeptide with a relative
      molecular mass of about 20 000 was obtained by limited proteolysis of rhMBLdeltaN
      fusion protein with thrombin. Repeated dialyses of rhMBLdeltaN polypeptides in 50
      mmol/L PBS and ddH(2)O resulted in the isolation of the trimeric subunit
      trhMBLdeltaN (with a relative molecular mass of about 50 000), which contained a
      collagen-like helix. The trhMBLdeltaN protein had a higher ligand-binding
      activity than rhMBLdeltaN polypeptide, and acquired the activity to initiate the
      lectin pathway of complement activation, but the activities were lower than those
      of natural MBL. CONCLUSION: We have successfully obtained the bioactive trimeric
      subunit of rhMBL, trhMBLdeltaN, and this structural subunit is also the
      functional subunit of the MBL molecule.

PMID- 23174581
TI  - [Finite element analysis of the initial stability of subtalar arthrodesis with
      double-screw fixation].
AB  - OBJECTIVE: To assess the optimal configuration of double-screw fixation for
      subtalar arthrodesis using finite element analysis. METHODS: Three-dimensional
      finite element double-screw models of subtalar arthrodesis were reconstructed
      using Mimics 13.0, Geomagic 10.0 and solid works software based on the 3-D images
      of the volunteer's right foot. The external and internal rotation torques of 4
      N.m were applied, and the micromotion at the bone-to-bone interface were measured
      to evaluate the initial stability of subtalar arthrodesis. RESULTS: A neck screw
      plus an anterolateral dome screw was the most stable model. The peak micromotion
      at the fusion site of this fixation configuration were 41.67mnplus;0.49 and
      42.64mnplus;0.75 um in response to the respectively. A neck screw plus a
      posteromedial dome screw was the least stable model, with peak micromotion at the
      bone-to-bone interface of 61.76mnplus;1.00 and 62.32mnplus;0.90 um, respectively.
      CONCLUSION: A neck screw plus an anterolateral dome screw is the best fixation
      configuration while a neck screw plus a posteromedial screw provides the least
      stability of subtalar arthrodesis. Three-dimensional finite element models allow
      effective preoperative planning of the screw number and placement.

PMID- 23174582
TI  - [Applied anatomy of the reverse pedicled island skin flap with arterial arch at
      the superior border of the abductor hallucis muscle for repairing fore foot skin
      defect].
AB  - OBJECTIVE: To explore the blood supply of the reverse arterial arch at the
      superior border of the hallucal abductor island flap and provide an anatomical
      basis for repairing fore foot skin defect using this flap. METHODS: The
      constitution, course, distribution, and external diameter of the arterial arch at
      the superior border of the hallucal abductor, and the concomitant veins and
      nerves were observed on 12 sides of formaldehyde-fixed and 12 fresh adult foot
      specimens perfused with red latex. The surgical approach using the arterial arch
      at the superior border of the hallucal abductor for repairing fore foot skin
      defect were designed. RESULTS: The arterial arch at the superior border of the
      hallucal abductor, constituted by the branch of the medial tarsal artery or the
      branch of the anterior medial malleolus artery anastomosed with the superficial
      branch of the medial basal hallucal artery or the branch of the superficial
      branch of the medial plantar artery or the all the four branches, functioned as
      the axis of the medial tarsal, the medialis pedis and the medial plantar. The
      external diameters of the anterior medial malleolus artery, the medial tarsal
      artery, the branch of the superficial branch of the medial plantar artery, and
      the distal arterial arch at the superior border of the hallucal abductor were
      1.02?0.03 mm, 0.73?0.04 mm, 0.56?0.02 mm, and 0.53?0.14 mm, respectively. Most of
      the arteries (91.67%) had one concomitant vein with the external diameters of
      1.01?0.03 mm, 0.81?0.04 mm, 0.57?0.01 mm, and 0.61?0.02, respectively, and only a
      small fraction of them (8.33%) had two concomitant veins. CONCLUSIONS: The fore
      foot skin defect can be repaired using this flap supplied by the branch of the
      anterior medial malleolus artery and the medial tarsal artery, the superficial
      branch of the medial plantar artery, or all the three. The pivot point formed by
      the neck of the first metatarsal or metatarsophalangeal joint allows for long
      vessel pedicles and larger flap areas to increase the flexibility of surgery.

PMID- 23174583
TI  - [Effect of Baitouweng Decoction on intestinal miR-19a expression in mice with
      ulcerative colitis].
AB  - OBJECTIVE: To investigate the therapeutic effect of Baitouweng Decoction on 
      dextran sodium sulphate (DSS)-induced ulcerative colitis in mice and explore its
      mechanism involving miR-19a. METHODS: Forty female c57 mice were randomly
      allocated into 4 equal groups, namely the normal control group, model group
      (treated with 3.5% DSS solution), treatment group (treated with DSS+Baitouweng
      Decoction), and positive control group (treated with DSS+5-ASA). Ulcerative
      colitis was induced in the mice by feeding them with 3.5% DSS in drinking water,
      and the mice in the control group were given water only. The disease activity
      index (DAI) of the mice in each group was recorded daily. Seven days later, the
      mice were sacrificed for histological examination of the intestines using HE
      staining; the expression of miR-19a mRNA in the intestines was detected using RT
      qPCR. RESULTS: Compared with the control group, the model group showed 
      significantly increased DAI and histological scores, and administration of
      Baitouweng Decoction significantly lowered the DAI and histological scores of the
      DSS-treated mice. The expression of miR-19a was lowered following DSS treatment,
      and Baitouweng Decoction treatment caused an increased miR-19a expression in DSS
      treated mice. CONCLUSION: Baitouweng Decoction has therapeutic effects on DSS
      induced ulcerative colitis in mice, and this effect is probably mediated by
      enhancement of miR-19a expression in the intestines.

PMID- 23174584
TI  - [Atorvastatin prevents contrast agent-induced renal injury in patients undergoing
      coronary angiography by inhibiting oxidative stress].
AB  - OBJECTIVE: To evaluate the efficacy of atorvastatin in preventing contrast agent
      induced nephropathy (CIN) in patients undergoing coronary angiography and explore
      the mechanism. METHODS: A total of 180 patients undergoing coronary angiography
      or percutaneous coronary interventions (PCI) were randomized into regular dose
      and high dose atorvastatin groups (n=90). Serum creatinine (Scr), glomerular
      filtration rate (GFR), cystatin, peripheral blood levels of myeloperoxidase
      (MPO), malondialdehyde (MDA), and superoxide dismutase (SOD)  before and after
      the procedure were compared between the two groups. RESULTS: The incidence of CIN
      was significantly lower in high-dose atorvastatin group than in the regular dose
      group. At 48-72 h after the surgery, serum Scr and cystatin levels were
      significantly lower and eGFR was significantly higher in the high-dose group. At
      24 h after the surgery, MPO and MDA levels were significantly lower, and SOD
      activity was significantly higher in high-dose group than in the regular dose
      group. CONCLUSION: High-dose atorvastatin used before angiography is more
      effective than the regular dose in attenuating contrast agent-induced renal
      dysfunction, and its mechanism is related with the inhibition of oxidative
      stress.

PMID- 23174585
TI  - [Effect of astragali injection on epithelial sodium channel expression in mice
      with acute lung injury].
AB  - OBJECTIVE: To investigate the effect of astragali injection on the expression of
      epithelial sodium channel in mice with acute lung injury (ALI) and explore the
      possible mechanism. METHODS: Thirty C57BL/6 mice were randomized into 3 equal
      groups, namely the control group, ALI model group, and astragali injection
      treatment group. Twelve hours after the treatments, The wet-dry ratio (W/D) of
      the lungs, inflammation cell percentages in the bronchoalveolar lavage fluid
      (BALF) and histopathological changes of the lung tissues were examined, and the
      expressions of alpha-ENaC, TNF-alpha, and IL-8 mRNA in the lung tissues were
      determined with quantitative RT-PCR. RESULTS: The neutrophil percentage in the
      BALF increased significantly in ALI group as compared with that in the other two
      groups. Pathological examination revealed milder lung tissue inflammation,
      congestion and edema in astragalus injection treatment group than in the ALI
      model group. Compared with those in the control group, alpha-ENaC mRNA expression
      decreased significantly while TNF-alpha and IL-8 mRNAs increased markedly in ALI
      group. In astragalus injection treatment group, the expression level of alpha
      ENaC mRNA was higher than that in ALI group, and TNF-alpha and IL-8 mRNA
      expression lower than those in ALI group but higher than those in the control
      group. CONCLUSION: Astragalus injection can ameliorate ALI in mice by inhibiting
      the release of inflammatory factors and up-regulating ENaC mRNA expression to
      promote the clearance of pulmonary edema fluid.

PMID- 23174586
TI  - [A fast non-local means algorithm for denoising of computed tomography images].
AB  - A fast non-local means image denoising algorithm is presented based on the single
      motif of existing computed tomography images in medical archiving systems. The
      algorithm is carried out in two steps of prepossessing and actual possessing. The
      sample neighborhood database is created via the data structure of locality
      sensitive hashing in the prepossessing stage. The CT image noise is removed by
      non-local means algorithm based on the sample neighborhoods accessed fast by
      locality sensitive hashing. The experimental results showed that the proposed
      algorithm could greatly reduce the execution time, as compared to NLM, and 
      effectively preserved the image edges and details.

PMID- 23174587
TI  - [Effect of intensive rosuvastatin therapy on adhesion molecules and the upstream
      mechanism in patients with peripheral atherosclerosis].
AB  - OBJECTIVE: To investigate the effect of intensive rosuvastatin therapy on
      adhesion molecules in patients with peripheral atherosclerosis and explore the
      possible upstream mechanism. METHODS: Twenty asymptomatic patients with
      peripheral atherosclerosis were enrolled and given 5-20 mg/day rosuvastatin for 3
      months. Before and after the treatment, the lipid profile and plasma vascular
      cell adhesion molecule-1 (VCAM-1) levels were examined. The expression of
      intercellular adhesion molecule-1 (ICAM-1) in the mononuclear cells was measured
      using flow cytometry, and the mRNA and protein expressions of peroxisome
      proliferator-activated receptor gamma (PPARgamma) were detected using RT-PCR and
      Western blotting, respectively. RESULTS: Compared with the baseline levels, ICAM
      1 expression decreased and PPARgamma protein expression increased in the
      lymphocytes. Rosuvastatin therapy did not produce obvious effects on plasma VCAM
      1 level or ICAM-1 expression in the monocytes in these patients. CONCLUSION:
      Rosuvastatin produces anti-inflammatory effects by decreasing the expression of
      ICAM-1 in mononuclear cells, and its upstream mechanism may involve the PPARgamma
      pathway.

PMID- 23174588
TI  - [Value of (18)F-FDG PET/CT and CECT in detecting postoperative recurrence and
      extrahepatic metastasis of hepatocellular carcinoma in patients with elevated
      serum alpha-fetoprotein].
AB  - OBJECTIVE: To assess the clinical value of (18)F-FDG PET/CT and contrast-enhanced
      computed tomography (CECT) in detecting residual tumor or tumor recurrence and
      metastasis in patients with hepatocellular carcinoma (HCC) who show an elevated
      serum alpha-fetoprotein (AFP) level after surgical intervention. METHODS: The
      data of (18)F-FDG PET/CT and CECT, which were performed at an interval within 2
      weeks, were reviewed in 54 HCC patients showing elevated AFP levels after
      surgical interventions of the tumor. The patients were followed up for at least 6
      months and the imaging findings were confirmed by pathological examination,
      follow-up imaging examination, or serum AFP level monitoring. RESULTS: Forty-five
      patients were found to have focal intrahepatic HCC recurrence after surgical
      interventions, and 9 patients were free of HCC recurrence. Twenty-three patients
      developed extrahepatic metastasis, among whom 19 also had intrahepatic tumor
      recurrence and 4 had extrahepatic metastasis only. The sensitivity, specificity,
      and accuracy of (18)F-FDG PET/CT in the detection of HCC recurrence were 88.9%
      (40/45), 77.8% (7/9), and 87.0% (47/54), respectively, as compared with those of
      57.8% (26/45), 100% (9/9), and 64.8% (35/54) by CECT detection. CONCLUSION:
      Compared with CECT, (18)F-PET/CT shows a high sensitivity and accuracy in
      detecting postoperative tumor residual or recurrence in the liver, and can also
      be an effective modality for detecting extrahepatic lesions in HCC patients.

PMID- 23174589
TI  - [Effects of ulinastatin on cardiac function and myocardial p38MAPK in rats with
      septic shock].
AB  - OBJECTIVE: To investigate the effect of different doses of ulinastatin (UTI) on
      the cardiac function and myocardial expression of p38 mitogen-activated protein
      kinase (p38MAPK) in septic rats. METHODS: Forty male SD rats were randomized
      equally into 5 groups, namely the control group (group A), sham-operated group
      (group B), sepsis group (group C), low-dose UTI group (group D), and high-dose
      UTI group (group E). Rat models of sepsis were established by cecal ligation and
      puncture (CLP), At 24 h after successful modeling, the left ventricle ejection
      fraction (LVEF) and fractional shortening (LVFS) were evaluated, and the
      myocardium of the left ventricle was sampled to examine the expression of the
      expressions of p38MAPK and p-p38MAPK using Western blotting. RESULTS: In groups
      A, B, C, D, and E, the LVEF was (77.13?3.76)%, (76.88?3.64)%, (56.13?4.16)%,
      (55.00?3.12)%, and (66.50?3.46)%, and the LVFS was (43.50?3.70)%, (44.00?3.38)%,
      (28.13?1.81)%, (26.13?2.70)%, and (38.00?2.07)%, respectively. Compared with
      group B at 24 h after CLP, LVEF and LVFS were markedly lowered in the groups C, D
      and E (P=0.000, 0.000 and 0.002), but showed no significant differences between
      groups C and D (P=0.541 and 0.166); LVEF and LVFS were significantly lower in
      group E than in groups C and D (P=0.000 and 0.000). The p-p38/p38 ratio was
      similar between groups C and D (0.79?0.12 vs 0.75?0.12, P=0.682), but both
      significantly higher than that in group B (0.28?0.15, P=0.001); the ratio in
      group E was significantly lower than that in group C (P=0.001), but similar with
      that in group B (P=0.972). CONCLUSION: High-dose UTI can inhibit p38
      phosphorylation, which may be the mechanism for its effect of myocardial
      protection in septic rat.

PMID- 23174590
TI  - [Effect of propofol and inhalation anesthesia on postoperative cognitive
      dysfunction in the elderly: a meta-analysis].
AB  - OBJECTIVE: To compare the effects of propofol and inhalation anesthesia on the
      incidence of early postoperative cognitive dysfunction (POCD) in elderly patients
      undergoing noncardiac surgeries. METHODS: PubMed, Cochrane Library, CBM, CNKI,
      Wanfang data and VIP Database (by October 2012) were searched for randomized
      controlled trials (RCTs) comparing propofol and inhalation anesthesia for their
      impact on the incidence of early POCD in elderly patients undergoing noncardiac
      surgeries. After data extraction and quality evaluation, Stata 12.0 software was
      used for statistical data analysis. RESULTS: Thirteen RCTs, including 2 comparing
      propofol with xenon, 7 comparing propofol with sevoflurane, and 4 comparing
      propofol with isoflurane were obtained, involving a total of 753 patients. The
      odds ratio of early POCD incidence between patients with propofol anesthesia and
      those with xenon anesthesia, sevoflurane anesthesia, and isoflurane anesthesia
      were 1.62 (95% CI 0.81-3.23, P=0.533), 0.67 (95% CI 0.39-1.14, P=0.830), and 0.20
      (95% CI 0.08-0.50, P=0.925), respectively. Overall, the odds ratio of early POCD
      incidence between propofol anesthesia and inhalation anesthesia was 0.68 (95% CI
      0.47-0.98, P=0.189). Egger's test showed a publication bias of the RCTs retrieved
      (P=0.011). CONCLUSION: Compared with inhalation anesthesia, propofol anesthesia
      is associated with a lower incidence of early POCD in elderly patients, but this
      conclusion needs to be further verified by more well-designed large-scale RCTs.

PMID- 23174591
TI  - [Expression of miR-216a in pancreatic cancer and its clinical significance].
AB  - OBJECTIVE: To explore the clinical significance of miRNA-216a expression in
      pancreatic cancer. METHODS: Fourteen patients with pancreatic cancer undergoing
      pancreaticoduodenectomy and 6 patients with benign pancreas lesions were examined
      for miR-216a expressions in the tumor or lesion tissues using Agilent Human miRNA
      Microarray (V12.0). The relationship between miR-216a expressions and the
      clinicopathological features of the patients was analyzed. RESULTS: The
      expression of miRNA-216a was significantly lower in pancreatic cancer than in
      benign pancreas lesions (P=0.000). The expression of miRNA-216a was significantly
      correlated with the T stage of the tumor (P=0.002), but not with the patients'
      age, gender, smoking status, tumor stage, lymph node metastases, distant
      metastasis, tumor differentiation, nerve invasion, vessel invasion or serum CA19
      9 level (P>0.05). CONCLUSIONS: The down-regulated expression of miR-216a in
      pancreatic cancer suggests the involvement of miR-216a in the tumorigenesis and
      development of pancreatic cancer. miR-216a may potentially serve as a novel tumor
      marker and also a prognostic factor for pancreatic cancer.

PMID- 23174592
TI  - [Effect of house dust mite vaccine on pulmonary function and inhaled
      corticosteroid doses in children with allergic asthma].
AB  - OBJECTIVE: To observe the dynamic changes of pulmonary function and inhaled
      corticosteroid (ICS) doses during subcutaneous immunotherapy (SCIT) with
      standardized house dust mite vaccine (Alutard) in children with mild to moderate
      allergic asthma. METHODS: One hundred children with mild to moderate allergic
      asthma were randomized into SCIT group and control group for treatment with SCIT
      plus ICS and with ICS only, respectively. The pulmonary function and ICS doses
      were evaluated before and every 3 months during the 2 years of treatment.
      RESULTS: No significant difference was found in the pulmonary functions between
      the two groups before the treatment (P>0.05). After 3 months of treatment, FEV1%
      and PEF% in SCIT group were significantly higher than those in the control group
      [(103.19?2.07)% vs (97.52?1.92)%, and (105.56?3.21)% vs (96.35?2.7)%,
      respectively]; at 21 months, FEF50% and FEF25% were significantly higher in SCIT
      group than in the control group [(105.69?3.29)% vs (94.61?3.12)%, and
      (106.60?3.71)% vs (92.92?3.31)%, respectively]. A significant difference was
      found in ICS doses between SCIT group and the control group after 9 months of
      treatment (147.14?6.41 vs 170?4.95 ug/day, P<0.05), and the difference increased
      as the treatment prolonged. CONCLUSION: SCIT combined with ICS can improve the
      ventilation function of the large airways early after the commencement of
      treatment, but its effect on small airways can be delayed. SCIT for 2 years shows
      a good therapeutic effect and can reduce the doses of ICS in children with mild
      to moderate allergic asthma.

PMID- 23174593
TI  - [Expression of MDR1 gene in cancer stem cells in breast cancer tissues of
      different molecular subtypes].
AB  - OBJECTIVE: To investigate the association between MDR1 gene expression in breast
      cancer stem cells and the molecular subtypes of breast cancer tissue. METHODS:
      According to ER, PR, Her-2 and CK5/14 expression profiles, 153 breast cancer
      specimens were divided into 5 molecular molecular subtypes, in which the
      expression of MDR1 was detected to analyze the relationship between MDR1 gene
      expression and the subtypes of breast cancer stem cells. RESULTS: The expression
      of MDR1 in Luminal A subtype breast cancer was 0.26?0.04, which showed no
      significant difference from that of Luminal B subtype (0.31?0.03, P>0.05).
      Compared with these two subtypes, HER-2 (+) subtype breast cancer tissues showed
      a significantly higher MDR1 expression(0.56?0.05, P<0.05). MDR1 expression in
      Basal-like subtype and Normal-like subtype breast cancers was comparable
      (0.98?0.01 vs 0.90?0.15, P<0.05), but both significantly higher than that in
      Luminal A and B subtypes and HER-2 (+) subtype (P<0.05). CONCLUSION: The
      expression of MDR1 gene in cancer stem cells is related with the molecular
      subtypes of breast cancer tissue.

PMID- 23174594
TI  - [Diffusion tensor imaging  of the bilateral uncinate fasciculus in patients with
      temporal lobe epilepsy].
AB  - OBJECTIVE: To study the structural integrity and continuity of the bilateral
      uncinate fasciculus (UF) in patients with temporal lobe epilepsy (TLE) using
      magnetic resonance diffusion tensor imaging (DTI) and evaluate the impact of
      structural damage of the UF on the executive function of the patients. METHODS:
      Thirty patients with TLE (14 left, 16 right) and 15 healthy control subjects
      underwent DTI scanning between January, 2007 and July, 2011, and the left and
      right UF were analyzed for fractional anisotropy (FA) and fiber mean length.
      RESULTS: In the control subjects, the average FA was significantly higher in the
      left than in the right UF (P<0.01). In patients with left TLE, the average FA of
      the left UF was significantly lower than that of the control subjects (P<0.01),
      but the FA of the right UF was comparable with that of the control group
      (P>0.05). In patients with right TLE, the average FA of the left and right UF was
      significantly lower than that of the control group (P<0.05 and P<0.01). In
      patients with unilateral TLE, the FA of their bilateral UF was similar. No
      significant difference was found in the mean length of UF fiber between these 3
      groups. CONCLUSIONS: FA is normally higher in the left UF than in the right UF,
      but inpatients with TLE, the left FA tends to have a lowered UF regardless of
      which hemisphere is involved, suggesting an early pathology in the microstructure
      of the left UF. This finding may help in the investigation of possible reasons
      for executive function damage in TLE patients.

PMID- 23174595
TI  - [Establishment of a mouse model of ovarian oxidative stress].
AB  - OBJECTIVE: To evaluate the feasibility of establishing a mouse model of ovarian
      oxidative stress by intraperitoneal injections of arsenic sodium. METHODS: Twenty
      adult female Kunming mice were randomized equally into the normal control group
      and ovarian oxidative stress model group for intraperitoneal injections of 0.5 ml
      distilled water and 8 mg/kg arsenic sodium solution every other day,
      respectively. After 8 injections, the mice were sacrificed for histological
      observation of the ovarian sections and enzyme-linked immunosorbent assay (ELISA)
      of serum estradiol (E(2)) and pregnenedione (P) levels ande contents of reactive
      oxygen species (ROS) , malondialdehyde (MDA), superoxide dismutase (SOD) and
      glutathione peroxidase (GSH-Px) in the ovary homogenate. RESULTS: Numerous
      atretic follicles were found in the ovaries of mice in the model group with
      obviously reduced growing follicles. Compared with those in the normal control
      group, the contents of ROS and MDA increased and SOD and GSH-Px levels in the
      ovarian homogenate decreased significantly in the model group (P<0.05).
      CONCLUSION: A mouse model of ovarian oxidative stress can be established by
      intraperitoneal injections of arsenic sodium.

PMID- 23174596
TI  - [Optimization of a lipopolysaccharide-stimulated nitric oxide production model in
      mouse peritoneal macrophages].
AB  - OBJECTIVE: To optimize the experimental model of nitric oxide (NO) production in
      mouse peritoneal macrophages in response to lipopolysaccharides (LPS)
      stimulation. METHODS: Mouse resident peritoneal macrophages were collected by
      lavaging the peritoneal cavity of mice with Hank's solution and stimulated with
      Pseudomonas aeruginosa LPS for NO production. NO concentration in the culture
      supernatants was measured with Griess Reagent. The influences of cell density,
      LPS concentration, LPS stimulation duration and culture medium volume on NO
      production were investigated. Finally, the feasibility of the model was confirmed
      with specific anti-inflammatory drugs. RESULTS: The density of macrophages
      produced the most significant effect on NO production (P<0.001), and optimal
      results were obtained at the macrophage density of 6*10(6) cells/ml with a volume
      of 100 ul in each well in 96-well plate. At a LPS concentration below 1 ug/ml, NO
      production increased proportionally with the increment of LPS concentration
      (P<0.001), but the increment of NO production declined obviously at LPS
      concentrations beyond 1 ug/ml, and the peak NO production occurred at a LPS
      concentration of 10 ug/ml. NO production also increased significantly with the
      prolongation of LPS stimulation (P<0.05), and the increments were greater within
      24-48 h than those in 48-72 h. NO content in the culture supernatant was
      associated with the medium volume, and the highest level occurred in a system
      volume of 100 ul. Aspirin (1 mmol/L), dexamethasone (10 umol/L), and cyclosporin
      A (10 umol/L) all significantly inhibited LPS-stimulated production of NO in
      mouse resident peritoneal macrophages (P<0.001). CONCLUSIONS: Macrophage density,
      LPS concentration, and the duration of LPS stimulation are the main factors
      affecting LPS-stimulated NO production in mouse resident peritoneal macrophages.
      The optimal results can be obtained with a macrophage density of 5*10(6) cells/ml
      (100 ul per well), LPS concentration of 10 ug/ml, LPS stimulation duration of 24
      h or 48 h, and a culture medium volume of 100 to 200 ul.

PMID- 23174598
TI  - [Positioning errors of CT common rail technique in intensity-modulated
      radiotherapy for nasopharyngeal carcinoma].
AB  - OBJECTIVE: To evaluate the value of CT common rail technique for application in
      intensity-modulated radiotherapy for nasopharyngeal carcinoma (NPC). METHODS:
      Twenty-seven NPC patients underwent Somatom CT scans using the Siemens CTVision
      system prior to the commencement of the radiotherapy sessions. The acquired CT
      images were registered with the planning CT images using the matching function of
      the system to obtain the linear set-up errors of 3 directions, namely X (left to
      right), Y (superior to inferior), and Z (anterior to posterior). The errors were
      then corrected online on the moving couch. RESULTS: The 27 NPC patients underwent
      a total of 110 CT scans and the displacement deviations of the X, Y and Z
      directions were -0.16?1.68 mm, 0.25?1.66 mm, and 0.33?1.09 mm, respectively.
      CONCLUSION: CT common rail technique can accurately and rapidly measure the space
      error between the posture and the target area to improve the set-up precision of
      intensity-modulated radiotherapy for NPC.

PMID- 23174597
TI  - [Exogenous putrescine causes renal function impairment and cell apoptosis in
      rats].
AB  - OBJECTIVE: To explore the effect of exogenous putrescine on renal function and
      cell apoptosis in rats. METHODS: Ninety SD rats were randomized into control
      group (n=10), high-dose putrescine group (P1 group, n=40), and low-dose
      putrescine group (P2 group, n=40) with intraperitoneal injections of 2 ml of
      normal saline, 50 ug/g putrescine, and 25 ug/g putrescine, respectively. At 24,
      48, 72 and 96 h after the injections, 10 rats from each group were sacrificed to
      examine serum Cr and BUN levels, histological changes in the kidneys, and renal
      cell apoptosis (TUNEL assay). RESULTS: The rats in the two putrescine- treated
      groups showed mild edema in some renal tissues without obvious necrosis. In P1
      and P2 groups, serum Cr and BUN levels differed significantly at each time point
      of measurement (P<0.01 and P<0.05, respectively), and were significantly higher
      than the levels in the control group (P<0.01 and P<0.05, respectively). The two
      putrescine-treated groups showed gradually increased renal cell apoptosis with
      time, reaching the peak levels at 96 h and 48 h, respectively. The peak renal
      cell apoptosis rates in P1 [(24.78?2.19)%] and P2 [(26.27?2.13)%] group were
      significantly higher than the rate in the control group [(4.47?0.33)%, P<0.01].
      CONCLUSION: Exogenous putrescine can lead to renal function impairment and induce
      renal cell apoptosis in rats, and the severity of these changes appeared to be
      associated with the blood concentration of exogenous putrescine.

PMID- 23174599
TI  - [Role of Ang-2, Tie-2 and VEGFR-2 in angiogenesis in colorectal carcinoma and
      their prognostic value].
AB  - OBJECTIVE: To study the expression of angiotensin-2 (Ang-2), Tie-2 and vascular
      endothelial growth factor receptor-2 (VEGFR-2) in colorectal cancer and analyze
      their relationship with the occurrence, recurrence, metastasis, angiogenesis and
      prognosis of colorectal cancer. METHODS: Immunohistochemistry with SP method was
      used to detect the expressions of Ang-2, Tie-2 and VEGFR-2 in 118 colorectal
      cancer, 40 adjacent normal tissue and 40 benign colorectal lesion specimens.
      RESULTS: The positivity rates of Ang-2, Tie-2 and VEGFR-2 in colorectal cancer
      tissue were 74.58%, 69.49%, and 61.02%, respectively, significantly higher than
      those in the adjacent normal tissues (25.00%, 17.50%, and 17.50%, P<0.05) and
      benign colorectal lesion tissues (35.00%, 32.50%, and 32.50%, P<0.05). The rates
      of two or three coexpression were significantly higher than that of a single
      expression in the cancer tissues (61.02% vs 15.25%). The microvascular density
      (MVD) of colorectal cancer tissues was 31.43?10.50, significantly higher than
      that of the adjacent normal tissues (10.61?3.76) and benign colorectal lesions
      (16.89?3.83) (P<0.05). The expressions of Ang-2, Tie-2, and VEGFR-2 were
      positively correlated with carcinoembryonic antigen (CEA) and MVD (P<0.05). The
      expression of Ang-2, but not Tie-2 and VEGFR-2, was positively correlated with
      CA199. Ang-2, Tie-2, and VEGFR-2 expressions showed significant differences
      between cases with tumor recurrence/metastasis and those without 5 years after
      radical mastectomy, and were all positively correlated with the 5-year survival
      rates (P<0.05). CONCLUSION: Ang-2, Tie-2 and VEGFR-2 are involved in the
      development, invasion, metastasis, and prognosis of colorectal cancer, and play
      important roles in the angiogenesis of the tumors.

PMID- 23174600
TI  - [Metastatic lymph node ratio and outcome of surgical patients with stage III
      colorectal cancer].
AB  - OBJECTIVE: Evaluate the prognostic value of lymph node ratio (LNR) in patients
      undergoing resection of stage III colorectal cancer. METHODS: The
      clinicopathological and follow-up data were collected from 174 surgical patients
      with stage III colorectal cancer. The 5-year disease-free survival (DFS) and
      overall survival (OS) were evaluated using Kaplan-Meier method. The impact of LNR
      and clinicopathological factors on DFS and OS were evaluated using univariate and
      multivariate analysis. RESULTS: After a median follow-up of 62.5 months, the 5
      year DFS and OS of the patients were 51.8% and 56.3%, respectively. The median
      number of lymph nodes harvested and the median number of positive lymph nodes
      examined were 10 and 3, respectively. The patients were stratified into 4 groups
      according to LNR quartiles (LNR1, LNR<=0.125; LNR2, 0.125<LNR<=0.260; LNR3,
      0.260<LNR<=0.500; LNR4, LNR>0.500), whose 5-year DFS and OS were 64.2%, 53.5%,
      41.8%, and 25.7% (P<0.05) and 68.1%, 60.8%, 49.2%, and 32.7% (P<0.05),
      respectively. Multivariate analysis identified age, T stage and LNR as the
      independent predictors of both DFS and OS. Subgroup analysis showed that LNR had
      an independent prognostic value on DFS and OS irrespective of the number of lymph
      nodes harvested. CONCLUSION: LNR is an independent prognostic factor for survival
      in patients with stage III colorectal cancer and is superior to the pN category
      in TNM staging.

PMID- 23174601
TI  - [Screening and identification of dengue virus type 2-specific antigens].
AB  - OBJECTIVE: To screen and identify dengue virus type 2 specific antigens and
      establish an enzyme-linked immunosorbent assay (ELISA) for detecting dengue virus
      type 2 antibody. METHODS: Using the bioinformatic software DNAstar and ANTHEPROT,
      we analyzed the hydrophilicity, flexibility, surface probability and antigenicity
      of dengue virus type 1-4, Japanese encephalitis virus, and Yellow fever virus M
      and E protein amino acid sequences, and also evaluated the influence of secondary
      structure. The specific epitopes of dengue virus type 2 were predicted according
      to the epitope location and amino acid sequence similarity, and the epitope
      conservation was assessed using the sequence information of different dengue
      virus type 2 strains in GenBank. Based on the results of bioinformatic analysis,
      5 specific epitopes were amplified and inserted into the prokaryotic expression
      vector pET32a, which were transferred into E. coli Rosetta (DE3) for expression
      of the proteins. SDS-PAGE and Western blotting were used to identify the
      expressed proteins and test their antigenicities. The antigen selected by Western
      blotting was used to establish the ELISA system for dengue virus type 2 antibody
      detection. RESULTS: Bioinformatic analysis predicted 8 possible dengue virus type
      2 specific epitopes, and 6 of them were efficiently expressed in E. coli. Western
      blotting confirmed 1 dengue virus type 2 specific antigen, the ELISA system for
      dengue virus antibody detection was successfully established using this specific
      antigen. CONCLUSION: We have obtained a dengue virus type 2 specific antigen and
      established an ELISA system for detection of dengue virus type 2 antibody.

PMID- 23174602
TI  - [Value of digital reconstruction technology in clinical classification of
      proximal humeral fractures].
AB  - OBJECTIVE: To explore the value of three-dimensional digital reconstruction
      techniques in the diagnosis and treatment of proximal humeral fractures. METHODS:
      From January, 2008 to May, 2010, 25 patients with proximal humeral fractures
      underwent preoperative examinations with conventional X-ray, plain CT scan and 3D
      CT scan. Based on the two-dimensional gray-scale CT scan data in DICOM format,
      personalized virtual fracture models were reconstructed using Amira4.1 software
      and compared with the conventional imaging examination methods for fracture
      typing to identify the fracture classification. Personalized surgical treatment
      was implemented according to the typing of the fractures, and the patients were
      followed up postoperatively for 8 to 35 months (mean 21 months) for functional
      evaluation using the Constant-Murley score. RESULTS: In the 25 cases of proximal
      humeral fractures, plain X-ray examination obtained a clear diagnosis and
      classification of the fractures in 15 cases, and CT scan, three-dimensional CT,
      and personalized three-dimensional model reconstruction confirmed the diagnosis
      and classification in 20, 22, and 25 cases, respectively. The humeral fractures
      healed generally 6 months after the operation, and the patients showed a Constant
      Murley score ranging from 70 to 100 (mean 88). CONCLUSIONS: Preoperative
      personalized three-dimensional reconstruction of proximal humeral fracture can
      help obtain a more accurate diagnosis of the fracture type to facilitate the
      decision on the optimal surgical plan, surgical approach and internal fixation
      methods.

PMID- 23174603
TI  - [Role of endoplasmic reticulum stress-related molecule GRP78 in global cerebral
      ischemia-reperfusion injury aggravated by hypertension in rats].
AB  - OBJECTIVE: To observe the changes in the expression of glucose-regulated protein
      78 (GRP78) in the hippocampus of normal rats and spontaneously hypertensive rats
      with cerebral ischemia/reperfusion (IR) and explore the possible role of GRP78 in
      global cerebral IR injury aggravated by hypertension. METHODS: Sixty male Wistar
      Kyoto (WKY) rats were randomly divided into sham operation group and global
      cerebral ischemia-reperfusion group(I/R) and a Another 30 male rats with
      spontaneous hypertension served as hypertensive cerebral ischemia and reperfusion
      (SHR+I/R) group. Global cerebral ischemia model was established in rats using a
      modified four-vessel occlusion method. The morphological changes of the neurons
      in the hippocampal region were observed using HE staining, and GRP78 expression
      was detected using immunohistochemistry and Western blotting. The behavioral
      changes of the rats were examined using the Eight-arm Maze. RESULTS: Compared
      with the rats with sham operation, the rats in I/R group showed a decreased
      density of surviving neurons in the hippocampus and an increased expression of
      GRP78, which reached the peak level at 24 h. Compared with that in I/R group, the
      density of surviving neurons decreased obviously at each time point in SHR+IR
      group, and GRP78 expression significantly increased at 6 h, followed then by
      progressive reduction at 24 and 48 h. The rats in SHR+IR group and I/R group
      showed no significant difference in behavior changes. CONCLUSION: Hypertension
      can aggravate global cerebral IR injury by decreasing GRP78 expression and
      increasing the loss of nerve cells.

PMID- 23174604
TI  - [Arthroscopy-assisted treatment of severe comminuted distal radial fracture using
      external fixators].
AB  - OBJECTIVE: To evaluate the outcomes of arthroscopy-assisted treatment of severe
      comminuted distal radial fracture with external fixators and kirschner wire
      fixation. METHODS: Twenty-seven cases of severe comminuted distal radial fracture
      treated between March, 2010 and January, 2012 were reviewed. During the
      operation, the carpal joint space was expanded with the external fixator, and the
      fracture was fixed by Kirschner wire after open reduction. The carpal joint was
      observed intraoperatively with arthroscopy to ensure full reduction, and the
      distal posterior interosseous nerve was then severed. The results of
      postoperative X-ray and wrist functional status of the carpal joints were
      recorded. Another 27 cases of severe comminuted distal radial fracture treated by
      conventional surgical approach served as the control group. RESULTS: The patients
      were followed up for a mean of 13.2 (5-27) months. Compared with the conventional
      surgical approach, arthroscopy-assisted treatment resulted in a significantly
      shorter operative time with better appearance of the articular surface and also
      better wrist function assessed using the Krimmer system (P<0.05). CONCLUSION:
      Arthroscopy-assisted external fixator treatment is effective for management of
      severe comminuted distal radial fracture and avoids the stair-like appearance of
      the articular surface to achieve the maximal functional recovery of the carpal
      joints and reduce traumatic arthritis.

PMID- 23174605
TI  - Elevated C1rC1sC1inh levels independently predict atherosclerotic coronary heart
      disease.
AB  - Clinical studies as well as animal models emphasized the importance of the
      complement system in the pathogenesis of coronary atherosclerosis and
      cardiovascular diseases. Our aim was to examine the extent and clinical
      implication of complement system activation in patients with stable
      atherosclerotic coronary heart disease (ACHD). Seventy-six patients with stable
      angina pectoris (SAP) scheduled for elective coronary angiography were enrolled
      into the study. Percutaneous coronary intervention (PCI) was performed in 24
      patients, in 27 patients (NOPCI group) the coronary angiography showed
      significant stenosis and bypass surgery (CABG) or optimal medical therapy (OMT)
      were advised, whereas in 25 patients the coronary angiography was negative (NC
      group). 115 volunteers served as healthy controls (HC). In all individuals, the
      plasma level of several complement activation products - C1rC1sC1inh, C3bBbP and
      SC5b-9 - were determined on admission, strictly before the coronary angiography.
      In patients with angiographically proven ACHD (PCI and NOPCI groups), the
      baseline C1rC1sC1inh levels were significantly higher compared to NC group and HC
      (p<0.0001, for both comparisons). According to the multiple logistic regression
      analysis, high C1rC1sC1inh level proved to be an independent biomarker of
      coronary heart disease (p<0.026, OR: 65.3, CI: 1.628-2616.284). CONCLUSION:
      Activation of the classical complement pathway can be observed in
      angiographically proven coronary atherosclerosis. Elevated C1rC1sC1inh levels
      might represent an useful biomarker for coronary artery disease.

PMID- 23174606
TI  - Autoimmune hepatitis: what must be said.
AB  - Autoimmune hepatitis (AIH) was first studied under its earlier name of "chronic
      active hepatitis" (CAH) from the 1950s, coincident with a renaissance of interest
      in autoimmunity. The definition of autoimmune serum reactants in disease,
      including CAH, gave new insights into chronic hepatitis and liver cirrhosis, and
      led to refinements of Burnet's clonal selection theory of acquired immunity, 1957
      59. Various discoveries including serological reactants in CAH prompted its
      designation in 1965 as autoimmune hepatitis, and treatment with immunosuppressive
      drug regimens transformed outcomes and survival. Serological observations further
      indicated that AIH could exist as either of two types, clinically similar but
      genetically different: Type 1 aligned more with the non-organ-specific
      multisystem diseases, and the infrequent Type 2 more with the organ-specific
      diseases. However, events in either type that could explain the onset of
      autoimmunity in the normally tolerogenic milieu of the liver have not been
      discerned. In the genetically predisposed individual, initiation may depend on
      non-specific death of hepatocytes after which fragments derived from disordered
      apoptosis acquire the capacity for ongoing auto-immunogenic stimulation.
      Insufficiency in numbers and function of Treg populations appears important in
      the promotion of this autoimmune process.

PMID- 23174607
TI  - Early childhood caries: risk-based disease prevention and management.
AB  - Early childhood caries (ECC), common in preschoolers, can lead to pain and
      infection if left untreated. Yet, ECC is largely preventable, and if it is
      identified early and the responsible risk factors are addressed, its progression
      can be halted or slowed. This article reviews the rationale for a first dental
      visit by age 1 year, caries risk assessment, and risk-based prevention and
      management of ECC and discusses strategies for providers to implement these
      contemporary evidence-based concepts into clinical practice.

PMID- 23174608
TI  - Periodontal considerations for children.
AB  - This article reviews periodontal disease and gingival disease and also explores
      issues relating to mucogingival defects such as gingival hyperplasia, gingival
      recession, and exposure of impacted canines.

PMID- 23174609
TI  - Overview of trauma management for primary and young permanent teeth.
AB  - This overview covers diagnosis and management of the most common dental injuries
      in children and identifies those children at greatest risk. Crown fractures and
      luxation injuries in both the primary and permanent dentition are discussed and
      treatment options based on current international guidelines are detailed.

PMID- 23174610
TI  - Vital pulp therapy.
AB  - Vital pulp therapy is performed to preserve the health status of the tooth and
      its ultimate position in the arch. These procedures are performed routinely in
      primary and permanent teeth. This review is divided into 2 parts: the first aims
      to illustrate the basic biology of the pulp and the effects on the pulp due to
      various procedures; the second focuses on the clinical aspects of treatment and
      the use of various dental materials during different vital pulp therapy
      procedures performed in the primary and permanent teeth.

PMID- 23174611
TI  - Restorative dentistry for children.
AB  - This article discusses contemporary pediatric restorative dentistry. Indications
      and contraindications for the choice of different restorative materials in
      different clinical situations, including the risk assessment of the patient, are
      presented. The specific use of glass ionomer cement or resin-modified glass
      ionomer cement, resin-based composite, and stainless steel crowns is discussed so
      that preparation design and restoration placement is understood.

PMID- 23174612
TI  - Pediatric oral and maxillofacial surgery.
AB  - Pediatric oral and maxillofacial surgery is rarely seen as a separate entity from
      adult oral and maxillofacial surgery. Many procedures are similar on adults and
      children; however, children have unique behavioral, anatomic, and physiologic
      considerations. Children also have a propensity for certain injuries and
      pathologic lesions. Children born with congenital anomalies may also have a
      special subset of needs. This article is a brief review of oral and maxillofacial
      surgery on the pediatric population.

PMID- 23174613
TI  - Temporomandibular joint disorders in children.
AB  - A child's difficulty in verbalizing the precise location and nature of facial
      pain and jaw dysfunction often results in a nondefinitive history, increasing the
      importance of the dentist's awareness of the early signs and symptoms of
      temporomandibular joint disorders (TMD). A focused examination of the masticatory
      musculature, the temporomandibular joints, and associated capsular and
      ligamentous structures can reveal if a patient's symptoms are TMD in origin. An
      accurate differential diagnosis enables timely referral to appropriate health
      care providers and minimizes the use of diagnostic imaging.

PMID- 23174614
TI  - The continuum of behavior guidance.
AB  - Behavior guidance is a continuum of techniques, basic and advanced, fundamental
      to the provision of quality dental care for pediatric patients. This practice
      must be individualized, pairing the correct method of behavior guidance with each
      child. To select the appropriate technique, the clinician must have a thorough
      understanding of each aspect of the continuum and anticipate parental
      expectations, child temperament, and the technical procedures necessary to
      complete care. By effectively using techniques within the continuum of behavior
      guidance, a healing relationship with the family is maintained while addressing
      dental disease and empowering the child to receive dental treatment throughout
      their lifetime.

PMID- 23174615
TI  - The role of sedation in contemporary pediatric dentistry.
AB  - Procedural sedation offers an effective and humane way to deliver dental care to
      the young, anxious child and to those with extensive treatment needs. Delivery of
      sedation requires thorough understanding of its indications and
      contraindications, patient assessment, pharmacology, monitoring, and office
      protocol. Safe and successful outcomes depend on a systematic approach to care,
      and the ability to manage unintended cardiopulmonary events.

PMID- 23174616
TI  - Providing dental treatment for children in a hospital setting.
AB  - This article discusses aspects of providing dental treatment in hospitals to
      patients with complex medical and/or behavioral problems. Practical information
      for patient selection for care in a hospital operating room, obtaining hospital
      privileges, and other aspects of dental care in hospitals are introduced.

PMID- 23174617
TI  - Pediatric dentistry.

PMID- 23174618
TI  - Chronic, but not acute, ethanol exposure impairs central hypercapnic ventilatory
      drive in bullfrog tadpoles.
AB  - Chronic ethanol exposure early in development is deleterious to neural
      development and may impair responses to ventilatory stimuli (ventilatory drive)
      that maintain homeostasis. Central hypercapnic ventilatory drive (CHVD) increases
      ventilation to ensure pH homeostasis and accommodate the metabolic production of
      CO(2). We tested the hypothesis that chronic ethanol exposure impairs CHVD in
      bullfrog tadpoles. Early and late metamorphic tadpoles were exposed in vivo to
      0.12-0.06 g/dL ethanol for either 3- or 10-wk durations. Brainstems from these
      animals were isolated and the neural correlates of ventilation were recorded in
      vitro during superfusion with normocapnic (1.5% CO(2):98.5% O(2)) and hypercapnic
      (5.0% CO(2):95.0% O(2)) artificial cerebral spinal fluid. Normocapnic
      neuroventilation was unaffected by chronic ethanol exposure. The typical response
      to hypercapnia, an increase in lung burst frequency, was lost following 10 but
      not 3 wk of ethanol exposure in both early and late metamorphic tadpoles. The
      neuroventilatory effects of chronic ethanol exposure were distinguishable from
      those of acute central ethanol (0.08 g/dL) exposure, which attenuated early
      metamorphic tadpole normocapnic neuroventilation, but had no effect on tadpole
      CHVD. Thus, 10 wk of ethanol exposure both early and late in metamorphosis
      impairs CHVD in bullfrog tadpoles.

PMID- 23174619
TI  - Analysis of heart rate variability and skin blood flow oscillations under deep
      controlled breathing.
AB  - The effect of deep breathing controlled in both rate (0.25, 0.16, 0.1, 0.07, 0.05
      and 0.03 Hz) and amplitude on the heart rate variability (HRV) and respiration
      dependent oscillations of forearm/finger skin blood flow (SBF) has been studied
      in 29 young healthy volunteers. The influence of sympathovagal balance on the
      respiratory sinus arrhythmia (RSA) amplitude and respiratory SBF oscillations has
      been studied. The subjects with predominant parasympathetic tonus had
      statistically significant higher RSA amplitudes in the breathing rate region of
      0.03-0.07 Hz than the subjects with predominant sympathetic tonus. In the finger
      cushion zone, having a well-developed sympathetic vascular innervations, the
      amplitudes of respiratory SBF oscillations at breathing rates 0.05 and 0.07 Hz
      were higher in the group of subjects with predominant parasympathetic tonus. In
      the forearm skin, where the density of sympathetic innervations is low
      comparatively to that in the finger skin, no statistically significant
      differences in the amplitude of respiratory SBF oscillations were found
      concerning the two groups of subjects.

PMID- 23174620
TI  - Platelet factor 4 and its modulatory effect on systemic carcinogenesis.

PMID- 23174621
TI  - Activated thrombin-activatable fibrinolysis inhibitor (TAFIa) levels are
      decreased in patients with trauma-induced coagulopathy.
AB  - INTRODUCTION: The thrombin-activatable fibrinolysis inhibitor (TAFI) is a potent
      inhibitor of fibrinolysis. However, the time course of TAFI and its activated
      form (TAFIa) following trauma, in particular in patients suffering trauma-induced
      coagulopathy, has been poorly examined. METHODS: A total of 26 severely injured
      trauma patients were prospectively enrolled. TAFI and TAFIa levels were measured
      upon arrival and through hospital days one to 10. Trauma-induced coagulopathy was
      defined as elevated international normalized ratio (INR), and/or prolonged
      activated partial thromboplastin time (aPTT) and/or thrombocytopenia within one
      day of admission. RESULTS: TAFIa and TAFI levels showed the largest decrease on
      days one and two, respectively, with a progressive increase thereafter. Overall,
      11 patients developed coagulopathy. No statistically significant differences were
      found for TAFI levels between the two groups. For TAFIa, however, coagulopathic
      patients experienced significantly lower levels on admission and on days six to
      eight (all p<0.05). Statistically significant correlations were found between
      TAFIa level on admission and the amount of packed red blood cells (p=0.011;
      Spearman's correlation coefficient=-0.5) and fresh frozen plasma (p=0.044;
      Spearman's correlation coefficient=-0.405) transfused within the initial 24hours.
      CONCLUSION: Depletion of TAFIa may contribute to the development of trauma
      induced coagulopathy.

PMID- 23174622
TI  - Adult-onset arterial thrombosis in a pedigree of homozygous and heterozygous
      protein C deficiency.

PMID- 23174623
TI  - Aliskiren inhibits experimental venous thrombosis in two-kidney one- clip
      hypertensive rats.
AB  - A substantial amount of evidence links the renin-angiotensin system with
      thrombosis. For example, ACE inhibitors and angiotensin receptor blockers possess
      independent of the hemodynamic changes, antithrombotic activity. Aliskiren direct
      renin inhibitor belongs to a new very promising antihypertensive drug that
      effectively inhibits the renin-angiotensin system. The aim of study was to
      determine the influence of aliskiren on stasis-induced venous thrombosis in
      renovascular hypertensive and normotensive rats. The involvement of nitric oxide
      and prostacyclin in the potential antithrombotic action was also elucidated. Six
      weeks after clipping of the left renal artery rats developed hypertension which
      was confirmed by the "tail cuff" method. Hypertensive and normotensive rats were
      treated with aliskiren (10, 30 and 100mg/kg/day) per os for 10days. Venous
      thrombosis was induced by stasis of vena cava inferior. Aliskiren at the highest
      dose induced a significant decrease in systolic blood pressure in hypertensive,
      but did not change this parameter in normotensive rats. Oral administration of
      aliskiren resulted in dose-dependent decrease of venous thrombus weight in
      hypertensive and normotensive rats. The antithrombotic activity of aliskiren was
      abolished both by NO synthase inhibitor and prostacyclin synthesis inhibitor.
      Aliskiren decreased collagen-induced platelet aggregation, increased plasma level
      of tissue plasminogen activator activity whereas no changes in plasminogen
      activator inhibitor activity and coagulation parameters were found. We showed
      that aliskiren prevents the development of venous thrombosis by enhanced
      fibrinolysis and the blood platelet inhibition via nitric oxide and/or
      prostacyclin-dependent mechanism.

PMID- 23174624
TI  - Circulating and vein wall P-selectin promote venous thrombogenesis during aging
      in a rodent model.
AB  - INTRODUCTION: The objective of this study was to identify the direct relationship
      between aging and selectin activation during acute venous thrombosis in mice of
      varying ages. We hypothesized that older animals would have increased venous
      thrombus formation as a result of age associated-increases of pro-inflammatory
      molecules within the vein wall when compared to younger animals. MATERIALS AND
      METHODS: Deep venous thrombosis (DVT) was induced in 4 and 18month old C57BL/6
      mice using the electrolytic inferior vena cava model (EIM) of DVT. Blood and
      tissue samples were collected at baseline (TC), 6hours, and 2days post-thrombosis
      induction. RESULTS: Older mice had significantly larger thrombi versus younger
      mice at 6H (18.4+/-6.21 vs. 13.0+/-4.29*10(-3) grams, p=0.0033) and 2D (18.4+/
      4.27 vs. 13.0+/-5.01*10(-3) grams, p=0.0005), higher soluble P-selectin levels at
      6H (13+/-2.5 vs. 8.4+/-2.7ng/mg p=0.0010) and 2D (12.7+/-5.0 vs. 5.9+/-1.3ng/mg
      p=0.0020), and higher vein wall P-selectin levels at 6H (1.94*10(5)+/-3.56*10(4)
      vs. 4.81+/-2.29*10(4) pg/mg p=0.0001) and 2D (1.38*10(5)+/-5.65*10(4) vs. 3.73+/
      1.66*10(4) pg/mg p=0.0177). Older animals also had significantly higher platelet
      numbers at 6H (841+/-203.8 vs. 564+/-164.8K/MUL p=0.0001), and 2D (1002+/-342.9
      vs. 690+/-186.1K/MUL p=0.0003), with corresponding increases in mean platelet
      volume versus younger mice post thrombosis (p<=0.01). CONCLUSIONS: Older animals
      had significantly larger venous thrombi versus younger animals post-thombosis, as
      a result of high levels of P-selectin both in the circulation and locally at the
      level of the vein wall. Expression of local and soluble P-selectin increased with
      age, resulting in a pro-thrombotic environment not represented in younger mice.

PMID- 23174625
TI  - Collagen-induced thrombosis in large vessels using native prothrombotic
      substrates.

PMID- 23174626
TI  - The occurrence of venous thromboembolism in cancer patients following major
      surgery.
AB  - BACKGROUND: Venous thromboembolism (VTE), encompassing deep vein thrombosis (DVT)
      and pulmonary embolism (PE), is common in cancer patients and surgery is an
      important risk factor. OBJECTIVE: To describe the occurrence of VTE in cancer
      patients following major surgery and to determine the risk of VTE recurrence.
      METHODS: Using the administrative health claims (RAMQ) and hospital discharge
      (MED-ECHO) databases of the province of Quebec, Canada, we constructed a cohort
      of all individuals with incident VTE between January 1, 1994 and December 31,
      2004 diagnosed with cancer and who had major surgery in the 91days prior to the
      VTE. The timing of VTE after surgery was determined. Recurrent VTE was defined as
      re-hospitalization with a principal discharge diagnosis of VTE. RESULTS: Our
      cohort consisted of 2706 cancer patients with VTE following major surgery. The
      mean age was 65.9years (Standard Deviation 12.6) and 54% were female. The median
      duration of surgical hospitalization was 18days (range 1-735days). The median
      time to VTE following surgery was 15days (range 1-659days), and 34% of VTE events
      were diagnosed after hospital discharge. The 1-year cumulative rate of recurrence
      was 6.7% (95% CI 5.7, 7.9) and the 5-year cumulative rate was 12.6% (95% CI 10.7,
      14.7). Increasing comorbidity (adjusted hazard ratio (HR) 2.49, 95% CI 1.58-3.95)
      and VTE diagnosed after hospital discharge (adjusted HR 1.48, 95% CI 1.09-2.01)
      were associated with recurrence. CONCLUSIONS: A significant proportion of VTE
      episodes among surgical patients with cancer are diagnosed after discharge from
      hospital. This suggests that surgical patients with cancer are at risk for VTE
      beyond the immediate postoperative period.

PMID- 23174627
TI  - Artificial neural network modelling of the results of tympanoplasty in chronic
      suppurative otitis media patients.
AB  - The application of computer modelling for medical purposes, although challenging,
      is a promising pathway for further development in the medical sciences. We
      present predictive neural and k-nearest neighbour (k-NN) models for hearing
      improvements after middle ear surgery for chronic otitis media. The studied data
      set comprised 150 patients characterised by the set of input variables: age,
      gender, preoperative audiometric results, ear pathology and details of the
      surgical procedure. The predicted (output) variable was the postoperative hearing
      threshold. The best neural models developed in this study achieved 84% correct
      predictions for the test data set while the k-NN model produced only 75.8%
      correct predictions.

PMID- 23174628
TI  - Progress and directions in professional credentialing for health education in the
      United States.
AB  - This article provides an update on initiatives in individual certification and
      accreditation of academic programs in public/community health education and
      school health education in the United States. Although we provide some historical
      context, the focus primarily addresses credentialing efforts that have evolved
      since the Galway Consensus Conference was convened in 2008 and publication of the
      Galway Consensus and related manuscripts in 2009. Significant progress has been
      achieved in updating the health education competencies for entry and advanced
      levels of practice, as well as in establishing a Master Certified Health
      Education Specialist designation. Also discussed are contemporary initiatives to
      expand and improve the accreditation process of academic programs and the
      evolving higher education contexts in which such systems operate. We conclude by
      presenting lessons learned from the U.S. experience with credentialing efforts
      and by offering recommendations that may be applicable to future quality
      assurance efforts, both in the United States and abroad.

PMID- 23174629
TI  - Empowered diabetes management: life coaching and pharmacist counseling for
      employed adults with diabetes.
AB  - The Hawai'i Demonstration to Maintain Independence and Employment was a
      randomized controlled trial examining the effect of a participant-driven,
      multicomponent intervention on 190 employed adults with diabetes, 36% of whom
      were Asian and 35% of whom were Native Hawaiian or Pacific Islander. A no
      treatment concurrent control group was used, and the treatment group was provided
      an intervention that paired each participant with a life coach and a pharmacist
      counselor with whom they worked to achieve collaboratively chosen goals.
      Treatment fidelity data suggest that the intervention was largely implemented as
      planned. Life coaches and pharmacists performed key program functions with high
      to moderate adherence. The quality of their adherence to the intervention model
      ranged from basic to above basic and below basic to above basic for life coaches
      and pharmacists, respectively. Results of repeated-measures analysis of
      covariance analyses indicate that the intervention had a significant positive
      effect on participants' diabetes self-efficacy, quality of life, and body mass
      index but not on hemoglobin A1c levels. Further analyses examining just the
      treatment group indicate a dosage effect, with body mass index and quality of
      life outcomes optimized among participants who engaged in a greater number of
      sessions with life coaches and pharmacists. Implications of the study findings
      for practice are discussed. 

PMID- 23174630
TI  - Enterococcus faecalis internalization in human umbilical vein endothelial cells
      (HUVEC).
AB  - Initial Enterococcus faecalis-endothelial cell molecular interactions which lead
      to enterococci associating in the host endothelial tissue, colonizing it and
      proliferating there can be assessed using in vitro models. Cultured human
      umbilical vein endothelial cells (HUVEC) have been used to study other Gram
      positive bacteria-cell interactions; however, few studies have been aimed at
      establishing the relationship of E. faecalis with endothelial cells. The
      aggregation substance (AS) family of adhesins represents an E. faecalis virulence
      factor which has been implicated in endocarditis severity and bacterial
      persistence. The Asc10 protein (a member of this family) promotes bacterium
      bacterium aggregation and bacterium-host cell binding. Evaluating Asc10 role in
      bacterial internalization by cultured enterocytes has shown that this adhesin
      facilitates E. faecalis endocytosis by HT-29 cells. A few eukaryotic cell
      structural components, such as cytoskeletal proteins, have been involved in E.
      faecalis entry into cell-lines; it is thus relevant to determine whether Asc10,
      as well as microtubules and actin microfilaments, play a role in E. faecalis
      internalization by cultured endothelial cells. The role of Asc10 and cytoskeleton
      proteins in E. faecalis ability to enter HUVEC was assessed in the present study,
      as well as cell apoptosis induction by enterococcal internalization by HUVEC; the
      data indicated increased cell apoptosis and that cytoskeleton components were
      partially involved in E. faecalis entry to endothelial cells, thereby suggesting
      that E. faecalis Asc10 protein would not be a critical factor for bacterial entry
      to cultured HUVEC.

PMID- 23174631
TI  - Binding of Streptococcus gordonii to oral epithelial monolayers increases
      paracellular barrier function.
AB  - The junctional epithelium comprising the gingival attachment to the tooth acts as
      a barrier against pathogenic subgingival plaque microbes and their products.
      There is evidence that pathogenic Porphyromonas gingivalis has the potential to
      disrupt epithelial integrity, contributing to breakdown of the junctional
      epithelium characteristic of the immunopathological response of chronic
      periodontitis. The present study investigated the capacity of the oral commensal
      Streptococcus gordonii to increase epithelial barrier function to support
      epithelial integrity of healthy tissue. Oral epithelial barrier function was
      measured by permeability assay. Changes in expression of tight junction
      components were monitored by quantitative real-time RT-PCR and Western blot in an
      oral epithelial cell culture model following binding by S. gordonii strain FSS2.
      The data showed increased expression of genes encoding the tight junction
      components ZO-1, ZO-2, JAM-A, and occludin at a ratio of 100 bacterial colony
      forming units per epithelial cell. This was associated with increased expression
      at the protein level of ZO-1, ZO-2 and JAM-A. Reduction of permeability to
      fluorochrome-labelled dextran accompanied these changes. The data support the
      hypothesis that (some) commensal bacteria have a beneficial effect on oral
      epithelium.

PMID- 23174632
TI  - Development and validation of a stent thrombosis risk score in patients with
      acute coronary syndromes.
AB  - OBJECTIVES: This study sought to develop a practical risk score to predict the
      risk of stent thrombosis (ST) after percutaneous coronary intervention (PCI) for
      acute coronary syndromes (ACS). BACKGROUND: ST is a rare, yet feared complication
      after PCI with stent implantation. A risk score for ST after PCI in ACS can be a
      helpful tool to personalize risk assessment. METHODS: This study represents a
      patient-level pooled analysis of 6,139 patients undergoing PCI with stent
      implantation for ACS in the HORIZONS-AMI (Harmonizing Outcomes With
      Revascularization and Stents in Acute Myocardial Infarction) and ACUITY (Acute
      Catheterization and Urgent Intervention Triage Strategy) trials who were
      randomized to treatment with bivalirudin versus heparin plus a glycoprotein
      IIb/IIIa inhibitor. The cohort was randomly divided into a risk score development
      cohort (n = 4,093) and a validation cohort (n = 2,046). Cox regression methods
      were used to identify clinical, angiographic, and procedural characteristics
      associated with Academic Research Consortium-defined definite/probable ST at 1
      year. Each covariate in this model was assigned an integer score based on the
      regression coefficients. RESULTS: Variables included in the risk score were type
      of ACS (ST-segment elevation myocardial infarction, non-ST-segment elevation ACS
      with ST deviation, or non-ST-segment elevation ACS without ST changes), current
      smoking, insulin-dependent diabetes mellitus, prior PCI, baseline platelet count,
      absence of early (pre-PCI) anticoagulant therapy, aneurysmal/ulcerated lesion,
      baseline TIMI (Thrombolysis In Myocardial Infarction) flow grade 0/1, final TIMI
      flow grade <3, and number of treated vessels. Risk scores 1 to 6 were considered
      low risk, 7 to 9 intermediate risk, and 10 or greater high risk for ST. Rates of
      ST at 1 year in low-, intermediate-, and high-risk categories were 1.36%, 3.06%,
      and 9.18%, respectively, in the development cohort (p for trend <0.001), and
      1.65%, 2.77%, and 6.45% in the validation cohort (p for trend = 0.006). The C
      statistic for this risk score was over 0.65 in both cohorts. CONCLUSIONS: The
      individual risk of ST can be predicted using a simple risk score based on
      clinical, angiographic, and procedural variables. (Harmonizing Outcomes With
      Revascularization and Stents in Acute Myocardial Infarction [HORIZONS-AMI];
      NCT00433966) (Comparison of Angiomax Versus Heparin in Acute Coronary Syndromes
      [ACUITY]; NCT00093158).

PMID- 23174633
TI  - The appropriate use of risk scores.

PMID- 23174634
TI  - A new score for risk stratification of patients with acute coronary syndromes
      undergoing percutaneous coronary intervention: the ACUITY-PCI (Acute
      Catheterization and Urgent Intervention Triage Strategy-Percutaneous Coronary
      Intervention) risk score.
AB  - OBJECTIVES: This study sought to develop a new score specific for patients with
      non-ST-segment elevation acute coronary syndromes (NSTEACS) undergoing
      percutaneous coronary intervention (PCI) (the ACUITY-PCI [Acute Catheterization
      and Urgent Intervention Triage Strategy-Percutaneous Coronary Intervention] risk
      score). BACKGROUND: The TIMI (Thrombolysis In Myocardial Infarction) and GRACE
      (Global Registry for Acute Coronary Events) risk scores are recommended for risk
      stratification of patients with NSTEACS. However, these scores were not optimized
      for patients undergoing an early invasive strategy with PCI. METHODS: The ACUITY
      PCI risk score was created from data for 1,692 patients enrolled in the formal
      angiographic substudy of the ACUITY (Acute Catheterization and Urgent
      Intervention Triage Strategy) trial by integrating clinical, angiographic,
      laboratory, and electrocardiographic variables selected by multivariable
      analysis. The score was subsequently validated in a different population of 846
      patients and compared with the GRACE and TIMI risk scores, and the SYNTAX
      (Synergy Between PCI with Taxus and Cardiac Surgery) and Clinical SYNTAX scores.
      RESULTS: Six variables (2 clinical, 1 laboratory/electrocardiographic, and 3
      angiographic) were included in the ACUITY-PCI score: insulin-treated diabetes;
      renal insufficiency; baseline cardiac biomarker elevation or ST-segment
      deviation; bifurcation lesion; small vessel/diffuse coronary artery disease; and
      the extent of coronary artery disease. Event rates increased significantly across
      tertiles of ACUITY-PCI score. Compared with the other scores, the ACUITY-PCI
      score had the best discrimination (C-statistic), calibration (Hosmer-Lemeshow
      statistic), and index of separation. Moreover, the net reclassification
      improvement varied from 9% to 38% and the integrated discrimination index from
      1.9% to 2.7%. CONCLUSIONS: The ACUITY-PCI risk score is a new tool integrating
      clinical, angiographic, and laboratory/electrocardiographic variables
      specifically developed for patients with NSTEACS undergoing PCI. This score
      displayed better prognostic accuracy in terms of discrimination and calibration
      than other currently available scores for risk stratification of patients with
      NSTEACS. (Comparison of Angiomax Versus Heparin in Acute Coronary Syndromes
      [ACS]; NCT00093158).

PMID- 23174635
TI  - Walking beyond the GRACE (Global Registry of Acute Coronary Events) model in the
      death risk stratification during hospitalization in patients with acute coronary
      syndrome: what do the AR-G (ACTION [Acute Coronary Treatment and Intervention
      Outcomes Network] Registry and GWTG [Get With the Guidelines] Database), NCDR
      (National Cardiovascular Data Registry), and EuroHeart Risk Scores Provide?
AB  - OBJECTIVES: This study sought to compare the in-hospital prognostic values of the
      original and updated GRACE (Global Registry of Acute Coronary Events) risk score
      (RS) and the AR-G (ACTION [Acute Coronary Treatment and Intervention Outcomes
      Network] Registry and the GWTG [Get With the Guidelines] Database) RS in acute
      coronary syndromes (ACS). To evaluate the utility of recalculating risk after
      percutaneous coronary intervention (PCI) with newer RS models (NCDR [National
      Cardiovascular Data Registry] and EHS [EuroHeart Score] RS). BACKGROUND: Defined
      in 2003, GRACE is among the most popular systems of risk stratification in ACS.
      An updated version of GRACE has since appeared and new RS have been developed,
      aiming to improve risk prediction. METHODS: From 2004 to 2010, 4,497 consecutive
      patients admitted to a single center in Spain with an ACS were included (32.1% ST
      segment elevation myocardial infarction, 19.2% unstable angina). Discrimination
      (C-statistic) and calibration (Hosmer-Lemeshow [HL]) indexes were used to assess
      performance of each RS. A comparative analysis of RS designed to predict post-PCI
      mortality NCDR and EHS RS versus the GRACE and AR-G RS was performed in a
      subgroup of 1,113 consecutive patients included in the study. RESULTS: There were
      265 in-hospital deaths (5.9%). Original and updated GRACE RS and the AR-G RS all
      demonstrated good discrimination for in-hospital death (C-statistics: 0.91, 0.90
      and 0.90, respectively) with optimal calibration (HL p: 0.42, 0.50, and 0.47,
      respectively) in all spectra of ACS, according to different managements (PCI vs.
      conservative) and without significant differences between the 3 different RS. In
      patients undergoing PCI, EHS and NCDR RS (C-statistic = 0.80 and 0.84,
      respectively) were not superior to GRACE RS (C-statistic = 0.91), albeit in the
      subgroup of patients undergoing PCI who were categorized as high risk using the
      GRACE RS, both EHS and NCDR have contributed to decrease the false positive rate
      generated by using the GRACE RS. CONCLUSIONS: Despite having been developed over
      8 years ago, the GRACE RS still maintains its excellent performance for
      predicting in-hospital risk of death among ACS patients.

PMID- 23174636
TI  - Assessment of clinical, electrocardiographic, and physiological relevance of
      diagonal branch in left anterior descending coronary artery bifurcation lesions.
AB  - OBJECTIVES: This study sought to investigate the clinical, electrocardiographic,
      and physiological relevance of main and side branches in coronary bifurcation
      lesions. BACKGROUND: Discrepancy exists between stenosis severity and clinical
      outcomes in bifurcation lesions. However, its mechanism has not been fully
      evaluated yet. METHODS: Sixty-five patients with left anterior descending
      coronary artery (LAD) bifurcation lesions were prospectively enrolled. Chest pain
      and 12-lead electrocardiogram were assessed after 1-min occlusion of coronary
      flow and coronary wedge pressure (Pw) was measured using a pressure wire.
      RESULTS: ST-segment elevation was more frequent during LAD occlusion (92%) than
      during diagonal branch occlusion (37%) (p < 0.001). Pain score was also higher
      with the occlusion of LAD than with the diagonal branch (p < 0.001). However,
      both Pw and Pw/aortic pressure (Pa) were lower in the LAD than in diagonal
      branches (Pw: 21.0 +/- 6.5 vs. 26.7 +/- 9.4, p < 0.0001; Pw/Pa: 0.22 +/- 0.07 vs.
      0.27 +/- 0.08, p = 0.001). The corrected QT interval was prolonged with LAD
      occlusion (435.0 +/- 39.6 ms to 454.0 +/- 45.4 ms, p < 0.0001) but not with
      diagonal branch occlusion. There was no difference in vessel size between the
      diagonal branches with and without ST-segment elevation during occlusion.
      Positive and negative predictive values of vessel size (>=2.5 mm) to determine
      the presence of ST-segment elevation were 48% and 72%, respectively. CONCLUSIONS:
      Diagonal branch occlusion caused fewer anginas, less electrocardiogram change,
      less arrhythmogenic potential, and higher Pw than did a LAD occlusion. These
      differences seem to be the main mechanism explaining why aggressive treatment for
      side branches has not translated into clinical benefit in coronary bifurcation
      lesions. (Comparison Between Main Branch and Side Branch Vessels; NCT01046409).

PMID- 23174637
TI  - Randomized comparison of conservative versus aggressive strategy for provisional
      side branch intervention in coronary bifurcation lesions: results from the SMART
      STRATEGY (Smart Angioplasty Research Team-Optimal Strategy for Side Branch
      Intervention in Coronary Bifurcation Lesions) randomized trial.
AB  - OBJECTIVES: The authors sought to compare conservative and aggressive strategies
      for provisional side branch (SB) intervention in coronary bifurcation lesions.
      BACKGROUND: The optimal provisional approach for coronary bifurcation lesions has
      not been established. METHODS: In this prospective randomized trial, 258 patients
      with a coronary bifurcation lesion treated with drug-eluting stents were
      randomized to a conservative (n = 128) or aggressive (n = 130) SB intervention
      strategy. The criteria for SB intervention after main vessel stenting differed
      between the conservative and aggressive groups; Thrombolysis In Myocardial
      Infarction flow grade <3 versus diameter stenosis >75% for non-left main
      bifurcations and diameter stenosis >75% versus diameter stenosis >50% for left
      main bifurcations. The primary endpoint was target vessel failure (cardiac death,
      myocardial infarction, or target vessel revascularization) at 12 months. RESULTS:
      Left main bifurcation lesions were noted in 114 patients (44%) and true
      bifurcation lesions in 171 patients (66%). SB ballooning after main vessel
      stenting and SB stenting after SB ballooning were performed less frequently in
      the conservative group than in the aggressive group (25.8% vs. 68.5%, p < 0.001;
      and 7.0% vs. 30.0%, p < 0.001, respectively). The conservative strategy was
      associated with a lower incidence of procedure-related myocardial necrosis
      compared with the aggressive strategy (5.5% vs. 17.7%, p = 0.002). At 12 months,
      the incidence of target vessel failure was similar in both groups (9.4% in the
      conservative group vs. 9.2% in the aggressive group, p = 0.97). CONCLUSIONS:
      Compared with the aggressive strategy, the conservative strategy for provisional
      SB intervention was associated with similar long-term clinical outcomes and a
      lower incidence of procedure-related myocardial necrosis. (Optimal Strategy for
      Side Branch Stenting in Coronary Bifurcation Lesions [SMART-STRATEGY];
      NCT00794014).

PMID- 23174638
TI  - Clinical impact of second-generation everolimus-eluting stent compared with first
      generation drug-eluting stents in diabetes mellitus patients: insights from a
      nationwide coronary intervention register.
AB  - OBJECTIVES: This study sought to study the second-generation everolimus-eluting
      stent (EES) as compared with first-generation sirolimus-eluting (SES) and
      paclitaxel-eluting stents (PES) in diabetes mellitus (DM) patients. BACKGROUND:
      There are limited data available comparing clinical outcomes in this setting with
      EES and SES, whereas studies comparing EES with PES are not powered for low
      frequency endpoints. METHODS: All DM patients treated with EES, PES, or SES from
      January 18, 2007, to July 29, 2011, from the SCAAR (Swedish Coronary Angiography
      and Angioplasty Registery) were included. The EES was compared with SES or PES
      for the primary composite endpoint of clinically driven detected restenosis,
      definite stent thrombosis (ST), and all-cause mortality. RESULTS: In 4,751
      percutaneous coronary intervention-treated DM patients, 8,134 stents were
      implanted (EES = 3,928, PES = 2,836, SES = 1,370). The EES was associated with
      significantly lower event rates compared with SES (SES vs. EES hazard ratio [HR]:
      1.99; 95% confidence interval (CI): 1.19 to 3.08). The same was observed when
      compared with PES (PES vs. EES HR: 1.33; 95% CI: 0.93 to 1.91) but did not reach
      statistical significance. These results were mainly driven by lower incidence of
      ST (SES vs. EES HR: 2.87; 95% CI: 1.08 to 7.61; PES vs. EES HR: 1.74, 95% CI:
      0.82 to 3.71) and mortality (SES vs. EES HR: 2.02; 95% CI: 1.03 to 3.98; PES vs.
      EES HR: 1.69; 95% CI: 1.06 to 2.72). No significant differences in restenosis
      rates were observed between EES and SES or PES (SES vs. EES HR: 1.26; 95% CI:
      0.77 to 2.08; PES vs. EES HR: 1.05; 95% CI: 0.71 to 1.55). CONCLUSIONS: In all
      comer DM patients the use of EES was associated with improved outcomes compared
      with SES and PES mainly driven by lower rates of ST and mortality. These results
      suggest better safety rather than efficacy with EES when compared with SES or
      PES.

PMID- 23174639
TI  - Comparison of nonculprit coronary plaque characteristics between patients with
      and without diabetes: a 3-vessel optical coherence tomography study.
AB  - OBJECTIVES: The aim of the present study was to compare the characteristics of
      nonculprit coronary plaques between diabetes mellitus (DM) and non-DM patients
      using 3-vessel optical coherence tomography (OCT) imaging. BACKGROUND: DM
      patients have a higher recurrent cardiovascular event rate. METHODS: Patients who
      had undergone 3-vessel OCT imaging were identified from the Massachusetts General
      Hospital OCT Registry. Characteristics of nonculprit plaques were compared
      between DM and non-DM patients. RESULTS: A total of 230 nonculprit plaques were
      identified in 98 patients. Compared with non-DM patients, DM patients had a
      larger lipid index (LI) (averaged lipid arc * lipid length; 778.6 +/- 596.1 vs.
      1358.3 +/- 939.2, p < 0.001) and higher prevalence of calcification (48.4% vs.
      72.2%, p = 0.034) and thrombus (0% vs. 8.3%, p = 0.047). DM patients were divided
      into 2 groups based on glycated hemoglobin (A(1C)) levels of <=7.9% and >=8.0%.
      LI was significantly correlated with diabetic status (778.6 +/- 596.1 [non-DM]
      vs. 1,171.5 +/- 708.1 [A(1C) <=7.9%] vs. 1,638.5 +/- 1,173.8 [A(1C) >=8%], p
      value for linear trend = 0.005), and fibrous cap thickness was inversely
      correlated with the A(1C) level (99.4 +/- 46.7 MUm [non-DM] vs. 91.7 +/- 29.6 MUm
      [A(1C) <=7.9%] vs. 72.9 +/- 22.7 MUm [A(1C) >=8%], p value for linear trend =
      0.014). Patients with A(1C) >=8% also had the highest prevalence of thin-cap
      fibroatheroma (TCFA) and macrophage infiltration. CONCLUSIONS: Compared with non
      DM patients, DM patients have a larger LI and a higher prevalence of
      calcification and thrombus. The LI was larger and TCFA and macrophage
      infiltration were frequent in patients with A(1C) >=8%.

PMID- 23174641
TI  - Insulin resistance and ischemic myocardial injury post-percutaneous coronary
      interventions.

PMID- 23174640
TI  - Impact of insulin resistance on post-procedural myocardial injury and clinical
      outcomes in patients who underwent elective coronary interventions with drug
      eluting stents.
AB  - OBJECTIVES: This study sought to evaluate the associations between homeostatic
      indexes of insulin resistance (HOMA-IR) and post-procedural myocardial injury and
      clinical outcome after a percutaneous coronary intervention (PCI) with a drug
      eluting stent. BACKGROUND: Insulin resistance increases the risk of
      cardiovascular events. However, the association between insulin resistance and
      clinical outcome after coronary intervention is unclear. METHODS: We evaluated
      516 consecutive patients who underwent elective PCI with drug-eluting stents.
      Blood samples were collected from venous blood after overnight fasting, and
      fasting plasma glucose and insulin levels were measured. HOMA-IR was calculated
      according to the homeostasis model assessment. Post-procedural myocardial injury
      was evaluated by analysis of troponin T and creatine kinase-myocardial band
      isozyme levels hours after PCI. Cardiac event was defined as the composite
      endpoint of cardiovascular death, myocardial infarction, and any
      revascularization. RESULTS: With increasing tertiles of HOMA-IR, post-procedural
      troponin T and creatine kinase-myocardial band levels increased. In the multiple
      regression analysis, HOMA-IR was independently associated with troponin T
      elevation. During a median follow-up of 623 days, patients with the highest
      tertiles of HOMA-IR had the highest risk of cardiovascular events. The Cox
      proportional hazard models identified HOMA-IR as independently associated with
      worse clinical outcome after adjustment for clinical and procedural factors.
      CONCLUSIONS: These results indicated the impact of insulin resistance on post
      procedural myocardial injury and clinical outcome after elective PCI with drug
      eluting stent deployment. Evaluation of insulin resistance may provide useful
      information for predicting clinical outcomes after elective PCI.

PMID- 23174642
TI  - Time-dependent detrimental effects of distal embolization on myocardium and
      microvasculature during primary percutaneous coronary intervention.
AB  - OBJECTIVES: The authors sought to investigate the impact of distal embolization
      (DE) on myocardial damage and microvascular reperfusion, according to time-to
      treatment, using contrast-enhanced cardiac magnetic resonance (CE-CMR).
      BACKGROUND: DE, occurring during primary percutaneous coronary intervention (p
      PCI), appears to increase myocardial necrosis and to worsen microvascular
      perfusion, as shown by surrogate markers. However, data regarding the behavior of
      DE on jeopardized myocardium, and in particular on necrosis extent and
      distribution, are still lacking. METHODS: In 288 patients who underwent p-PCI
      within 6 h from symptom onset, the authors prospectively assessed the impact of
      DE on infarct size and microvascular damage, using CE-CMR. The impact of DE was
      assessed according to time-to-treatment: for group 1, <3 h; for group 2, >=3 and
      <=6 h. RESULTS: DE occurred in 41 (14.3%) patients. Baseline clinical
      characteristics were not different between the 2 groups. At CE-CMR, patients with
      DE showed larger infarct size (p = 0.038) and more often transmural necrosis
      compared with patients without DE (p = 0.008) when time-to-treatment was <3 h,
      but no impact was proven after this time (p = NS). Patients with DE showed more
      often microvascular obstruction, as evaluated at first-pass enhancement, than
      patients without DE (100% vs. 66.5%, p = 0.001) up to 6 h from symptom onset.
      CONCLUSIONS: These findings suggest that the detrimental impact of DE occurring
      during p-PCI on myocardial damage is largely influenced by ischemic time,
      increasing the extent of necrosis in patients presenting within the first hours
      after symptom onset, and having limited or no impact after this time window.

PMID- 23174643
TI  - Device closure of secundum atrial septal defects in children <15 kg: complication
      rates and indications for referral.
AB  - OBJECTIVES: This study sought to determine institutional complication rates in a
      previously underreported patient population and discuss referral indications.
      BACKGROUND: There has been a trend over the years for referral of younger and
      smaller patients for "elective" closure of atrial septal defects (ASD). In
      general, the risks associated with ASD device closure are believed and reported
      to be relatively low. Complication rates in this group of smaller patients are
      not well described in the literature for either percutaneous or surgical
      approaches. METHODS: Retrospective review of all patients who underwent elective
      transcatheter closure of secundum ASD between March 2000 and April 2010. We
      excluded all children >15 kg, as well as those with complex congenital heart
      defects. Major and minor complications were predefined and indications for
      referral were evaluated. RESULTS: We identified 128 patients meeting criteria
      with a median procedural age of 1.92 years (3 months to 4.92 years), and median
      weight of 10.8 kg (4.3 to 14.9 kb). There were 7 major (5.5%) and 12 minor (9.4%)
      complications. Nearly two-thirds of referrals were for right heart enlargement or
      poor growth. Rate of resolution of residual shunt was 99%. When compared with
      age, there was no difference in the rate of resolution of right heart
      enlargement. No clinically significant improvement in growth was observed.
      CONCLUSIONS: Transcatheter ASD closure in small children is highly successful,
      but with an increase in previously perceived complication rates. In small,
      asymptomatic patients, deferral of closure until the historically established
      timeline of around 4 to 5 years of age should be strongly considered.

PMID- 23174644
TI  - Concomitant anomalous right coronary artery and iatrogenic left circumflex artery
      entrapment, treated successfully with percutaneous coronary intervention.

PMID- 23174645
TI  - Optical coherence tomography assessment of coverage of side branch ostium after
      implantation of Xience SBA dedicated coronary bifurcation system.

PMID- 23174646
TI  - Percutaneous device closure of patent foramen ovale for cryptogenic
      strokes/transient ischemic attacks.

PMID- 23174648
TI  - Give me FREEDOM or...

PMID- 23174649
TI  - Image of a chronic recanalized thrombus by intracoronary imaging: intravascular
      ultrasound and optical coherence tomography analysis.

PMID- 23174650
TI  - Acute inferior myocardial infarction complicated by a very large ventricular
      septal rupture and cardiogenic shock.

PMID- 23174651
TI  - On the role of critique for science: a reply to Bao and Poppel.

PMID- 23174652
TI  - Effect of gloss and heat on the mechanical behaviour of a glass carbomer cement.
AB  - OBJECTIVES: The effect of gloss and heat on the mechanical behaviour of a
      recently launched glass carbomer cement (GCP, GCP dental) was evaluated and
      compared with resin-modified glass ionomer cements (Fuji II LC, GC and Photac Fil
      Quick Aplicap, 3M ESPE). METHODS: 120bar-shaped specimens (n=20) were produced,
      maintained in distilled water at 37 degrees C and tested after one week. The GCP
      specimens were cured with and without heat application and with and without
      gloss. The flexural strength and modulus of elasticity in flexural test as well
      as the micro-mechanical properties (Vickers Hardness, indentation modulus, creep)
      of the top and bottom surface were evaluated. The amount and size of the fillers,
      voids and cracks were compared using a light and a scanning electron microscope.
      RESULTS: In the flexural test, the resin-modified glass ionomer cements performed
      significantly better than GCP. Fuji II LC and Photac Fil (Weibull parameter: 17.7
      and 14.3) proved superior reliability in the flexural test compared to GCP (1.4
      2.6). The highest Vickers Hardness and lowest creep were achieved by GCP, whereas
      Fuji II LC reached the highest indentation modulus. The results of this study
      proved that relationships exist between the compositions, microstructures and
      mechanical properties of the cements. CONCLUSIONS: Heat treatment and gloss
      application did not influence the mechanical properties of GCP. The mechanical
      properties were basically influenced by the type of cement and its
      microstructure. CLINICAL SIGNIFICANCE: Considering the measured mechanical
      properties, there is no need of using gloss or heat when restoring teeth with
      GCP.

PMID- 23174653
TI  - pH-dependent kinetics of copper ions binding to amyloid-beta peptide.
AB  - Interactions of amyloid-beta peptide (Abeta) with Cu(2+) are known to be pH
      dependent and believed to play a crucial role in the neurotoxicity of Alzheimer's
      disease (AD). Some research has revealed that injured brains with lowered pH have
      higher risks of developing AD. However, reported experiments were performed under
      neutral or mildly acidic conditions, and no reports about the affinity of Abeta
      Cu(2+) below pH6.0. In this study, surface plasmon resonance (SPR) sensor with
      immobilized Abeta was used to investigate the formation of Abeta-Cu(2+) complexes
      under acidic pH conditions. Dissociation constants were calculated and shown to
      be pH-dependent, ranging from 3.5*10(-8)M to 8.7*10(-3)M in the pH range from 7.0
      to 4.0. The physiological significance of K(d) was preliminarily investigated by
      monitoring the generation of OH() in aerobic solutions containing Abeta-Cu(2+)
      and Cu(2+). The results imply that acidic conditions could aggravate the
      oxidative stress in the presence of Cu(2+), and the weak affinities of Abeta
      Cu(2+) under mildly acidic pH of 5.0-6.0 could further enhance the oxidative
      damage. However, the oxidative stress effect of Abeta is negligible due to the
      suppressed formation of Abeta-Cu(2+) below pH5.0. This work is useful for the in
      depth understanding of the role of Abeta-Cu(2+) in AD neuropathology.

PMID- 23174655
TI  - High throughput characterization of structural differences between closely
      related proteins in solution.
AB  - Partitioning of a protein in an aqueous two-phase system (ATPS) is governed by
      interactions of the protein with aqueous media in the two phases. Here we
      describe how partitioning of proteins in a set of ATPS of different compositions
      can be used to quantify differences between 3D structures of closely related
      proteins. We also provide perspective on practical applications of the technology
      when comparative analysis of the higher-order structure of proteins is desired.

PMID- 23174654
TI  - Development transitions of thin filament proteins in rat extraocular muscles.
AB  - Extraocular muscles are a unique subset of striated muscles. During postnatal
      development, the extraocular muscles undergo a number of myosin isoform
      transitions that occur between postnatal day P10 (P10) and P15. These include:
      (1) loss of embryonic myosin from the global layer resulting in the expression
      restricted to the orbital layer; (2) the onset of expression of extraocular
      myosin and the putative tonic myosin (myh 7b/14); and (3) the redistribution of
      nonmuscle myosin IIB from a subsarcolemmal position to a sarcomeric distribution
      in the slow fibers of the global layer. For this study, we examined the postnatal
      appearance and distribution of alpha-actinin, tropomyosin, and nebulin isoforms
      during postnatal development of the rat extraocular muscles. Although sarcomeric
      alpha-actinin is detectable from birth, alpha-actinin 3 appears around P15. Both
      tropomyosin-1 and -2 are present from birth in the same distribution as in the
      adult animal. The expression of nebulin was monitored by gel electrophoresis and
      western blots. At P5-10, nebulin exhibits a lower molecular mass than observed
      P15 and later during postnatal development. The changes in alpha-actinin 3 and
      nebulin expression between P10 and P15 coincide with transitions in myosin
      isoforms as detailed above. These data point to P10-P15 as the critical period
      for the maturation of the extraocular muscles, coinciding with eyelid opening.

PMID- 23174656
TI  - X-ray crystallography and QM/MM investigation on the oligosaccharide synthesis
      mechanism of rice BGlu1 glycosynthases.
AB  - Nucleophile mutants of retaining beta-glycosidase can act as glycosynthases to
      efficiently catalyze the synthesis of oligosaccharides. Previous studies proved
      that rice BGlu1 mutants E386G, E386S and E386A catalyze the oligosaccharide
      synthesis with different rates. The E386G mutant gave the fastest
      transglucosylation rate, which was approximately 3- and 19-fold faster than those
      of E386S and E386A. To account for the differences of their activities, in this
      paper, the X-ray crystal structures of BGlu1 mutants E386S and E386A were solved
      and compared with that of E386G mutant. However, they show quite similar active
      sites, which implies that their activities cannot be elucidated from the crystal
      structures alone. Therefore, a combined quantum mechanical/molecular mechanical
      (QM/MM) calculations were further performed. Our calculations reveal that the
      catalytic reaction follows a single-step mechanism, i.e., the extraction of
      proton by the acid/base, E176, and the formation of glycosidic bond are
      concerted. The energy barriers are calculated to be 19.9, 21.5 and 21.9kcal/mol
      for the mutants of E386G, E386S and E386A, respectively, which is consistent with
      the order of their experimental relative activities. But based on the calculated
      activation energies, 1.1kcal/mol energy difference may translate to nearly 100
      fold rate difference. Although the rate limiting step in these mutants has not
      been established, considering the size of the product and the nature of the
      active site, it is likely that the product release, rather than chemistry, is
      rate limiting in these oligosaccharides synthesis catalyzed by BGlu1 mutants.

PMID- 23174657
TI  - IL-22 suppresses IFN-gamma-mediated lung inflammation in asthmatic patients.
AB  - BACKGROUND: IL-22 controls tissue homeostasis by both proinflammatory and anti
      inflammatory effects. However, the anti-inflammatory mechanisms of IL-22 remain
      poorly investigated. OBJECTIVE: We sought to investigate the anti-inflammatory
      role for IL-22 in human asthma. METHODS: T-cell lines derived from lung biopsy
      specimens of asthmatic patients were characterized by means of flow cytometry.
      Human bronchial epithelial cells from healthy and asthmatic subjects were
      stimulated with IL-22, IFN-gamma, or the combination of both cytokines. Effects
      of cytokine stimulation were investigated by using whole-genome analysis, ELISA,
      and flow cytometry. The functional consequence of cytokine stimulation was
      evaluated in an in vitro wound repair model and T cell-mediated cytotoxicity
      experiments. In vivo cytokine expression was measured by using
      immunohistochemistry and Luminex assays in bronchoalveolar lavage fluid of
      healthy and asthmatic patients. RESULTS: The current study identifies a tissue
      restricted antagonistic interplay of IL-22 and the proinflammatory cytokine IFN
      gamma. On the one hand, IFN-gamma antagonized IL-22-mediated induction of the
      antimicrobial peptide S100A7 and epithelial cell migration in bronchial
      epithelial cells. On the other hand, IL-22 decreased epithelial susceptibility to
      T cell-mediated cytotoxicity by inhibiting the IFN-gamma-induced expression of
      MHC-I, MHC-II, and CD54/intercellular adhesion molecule 1 molecules. Likewise, IL
      22 inhibited IFN-gamma-induced secretion of the proinflammatory chemokines
      CCL5/RANTES and CXCL10/interferon-inducible protein 10 in vitro. Consistently,
      the IL-22 expression in bronchoalveolar lavage fluid of asthmatic patients
      inversely correlated with the expression of CCL5/RANTES and CXCL10/interferon
      inducible protein 10 in vivo. CONCLUSIONS: IL-22 might control the extent of IFN
      gamma-mediated lung inflammation and therefore play a tissue-restricted
      regulatory role.

PMID- 23174658
TI  - Identifying infants at high risk of peanut allergy: the Learning Early About
      Peanut Allergy (LEAP) screening study.
AB  - BACKGROUND: Peanut allergy (PA) is rare in countries in which peanuts are
      introduced early into infants' diets. Learning Early About Peanut Allergy (LEAP)
      is an interventional study aiming to assess whether PA can be prevented by oral
      tolerance induction. OBJECTIVE: We sought to characterize a population screened
      for the risk of PA. METHODS: Subjects screened for the LEAP interventional trial
      comprise the LEAP screening study cohort. Infants were aged 4 to 10 months and
      passed a prescreening questionnaire. RESULTS: This analysis includes 834 infants
      (mean age, 7.8 months). They were split into the following: group I, patients
      with mild eczema and no egg allergy (n = 118); group II, patients with severe
      eczema, egg allergy, or both but 0-mm peanut skin prick test (SPT) wheal
      responses (n = 542); group III, patients with severe eczema, egg allergy, or both
      and 1- to 4-mm peanut wheal responses (n = 98); and group IV, patients with
      greater than 4-mm peanut wheal responses (n = 76). Unexpectedly, many (17%) in
      group II had peanut-specific IgE sensitization (>= 0.35 kU/L); 56% of group III
      were similarly sensitized. In contrast, none of the patients in group I and 91%
      of those in group IV had peanut-specific IgE sensitization. Sensitization on skin
      testing to peanut (SPT response of 1-4 mm vs 0 mm) was associated with egg
      allergy and severe eczema (odds ratio [OR], 2.31 [95% CI, 1.39-3.86] and 2.47
      [95% CI, 1.14-5.34], respectively). Similar associations were observed with
      specific IgE sensitization. Black race was associated with a significantly higher
      risk of peanut-specific IgE sensitization (OR, 5.30 [95% CI, 2.85-9.86]).
      Paradoxically, for a given specific IgE level, black race was protective against
      cutaneous sensitization (OR, 0.15 [95% CI, 0.04-0.61]). CONCLUSION: Egg allergy,
      severe eczema, or both appear to be useful criteria for identifying high-risk
      infants with an intermediate level of peanut sensitization for entry into a PA
      prevention study. The relationship between specific IgE level and SPT
      sensitization needs to be considered within the context of race.

PMID- 23174659
TI  - Safety and efficacy of the prostaglandin D2 receptor antagonist AMG 853 in
      asthmatic patients.
AB  - BACKGROUND: The D-prostanoid receptor and the chemoattractant receptor homologous
      molecule expressed on T(H)2 cells (CRTH2) are implicated in asthma pathogenesis.
      AMG 853 is a potent, selective, orally bioavailable, small-molecule dual
      antagonist of human D-prostanoid and CRTH2. OBJECTIVE: We sought to determine the
      efficacy and safety of AMG 853 compared with placebo in patients with
      inadequately controlled asthma. METHODS: Adults with moderate-to-severe asthma
      were randomized to placebo; 5, 25, or 100 mg of oral AMG 853 twice daily; or 200
      mg of AMG 853 once daily for 12 weeks. All patients continued their inhaled
      corticosteroids. Long-acting beta-agonists were not allowed during the treatment
      period. Allowed concomitant medications included short-acting beta-agonists and a
      systemic corticosteroid burst for asthma exacerbation. The primary end point was
      change in total Asthma Control Questionnaire score from baseline to week 12.
      Secondary and exploratory end points included FEV(1), symptom scores, rescue
      short-acting beta-agonist use, and exacerbations. RESULTS: Among treated
      patients, no effect over placebo (n = 79) was observed in mean changes in Asthma
      Control Questionnaire scores at 12 weeks (placebo, -0.492; range for AMG 853
      groups [n = 317], -0.444 to -0.555). No significant differences between the
      active and placebo groups were observed for secondary end points. The most
      commonly reported adverse events were asthma, upper respiratory tract infection,
      and headache; 9 patients experienced serious adverse events, all of which were
      deemed unrelated to study treatment by the investigator. CONCLUSION: AMG 853 as
      an add-on to inhaled corticosteroid therapy demonstrated no associated risks but
      was not effective at improving asthma symptoms or lung function in patients with
      inadequately controlled moderate-to-severe asthma.

PMID- 23174660
TI  - Classification of primary immunodeficiencies: need for a revised approach?

PMID- 23174662
TI  - KRAS above and beyond - EGFR in pancreatic cancer.

PMID- 23174661
TI  - Programmed cell death ligand 2 regulates TH9 differentiation and induction of
      chronic airway hyperreactivity.
AB  - BACKGROUND: Asthma is defined as a chronic inflammatory disease of the airways;
      however, the underlying physiologic and immunologic processes are not fully
      understood. OBJECTIVE: The aim of this study was to determine whether TH9 cells
      develop in vivo in a model of chronic airway hyperreactivity (AHR) and what
      factors control this development. METHOD: We have developed a novel chronic
      allergen exposure model using the clinically relevant antigen Aspergillus
      fumigatus to determine the time kinetics of TH9 development in vivo. RESULTS: TH9
      cells were detectable in the lungs after chronic allergen exposure. The number of
      TH9 cells directly correlated with the severity of AHR, and anti-IL-9 treatment
      decreased airway inflammation. Moreover, we have identified programmed cell death
      ligand (PD-L) 2 as a negative regulator of TH9 cell differentiation. Lack of PD
      L2 was associated with significantly increased TGF-beta and IL-1alpha levels in
      the lungs, enhanced pulmonary TH9 differentiation, and higher morbidity in the
      sensitized mice. CONCLUSION: Our findings suggest that PD-L2 plays a pivotal role
      in the regulation of TH9 cell development in chronic AHR, providing novel
      strategies for modulating adaptive immunity during chronic allergic responses.

PMID- 23174663
TI  - Imprecision concerning the Global Trigger Tool.

PMID- 23174664
TI  - Health-related quality of life, disease severity, and anticipated trajectory of
      diabetes.
AB  - PURPOSE: Adults hospitalized with diabetes are likely to have multiple comorbid
      conditions contributing to suboptimal health-related quality of life. The purpose
      of this study was to survey urban, very low-income, hospitalized adults with
      diabetes about disease severity, anticipated disease trajectory, and self-rated
      health-related quality of life. METHODS: Data were collected using the Brief
      Illness Perception Questionnaire, the 36-item Short Form Health Survey (SF-36),
      the comparative risk perception questionnaire, and glycosylated hemoglobin.
      Severity was defined by glycosylated hemoglobin level and current microvascular
      complications from diabetes. FINDINGS: Those with more severe disease who also
      anticipated the development of additional diabetes-related complications were
      likely to have suboptimal physical and mental functioning. The perception of
      diabetes as a health threat concurrent with having non-diabetes-related comorbid
      chronic conditions contributed uniquely to explaining scores in health-related
      quality of life. CONCLUSION: Hospitalized adults with diabetes represent a
      population affected by chronic disease demands that contribute to suboptimal
      physical and mental functioning. Suboptimal quality of life may contribute to
      severity of diabetes and to a perception of having a threatening disease
      trajectory. Hospitalization provides an opportunity for clinicians to intervene
      in mental and physical functioning by assessing for threatening illness
      perceptions and employing interventions to promote acceptance of functional
      limitations.

PMID- 23174665
TI  - No filaggrin gene mutation in a patient with a combination of atopic dermatitis,
      alopecia areata and food allergy.

PMID- 23174666
TI  - Reply to letter from Dr. Kirby.

PMID- 23174667
TI  - Human pose recovery using wireless inertial measurement units.
AB  - Many applications in rehabilitation and sports training require the assessment of
      the patient's status based on observation of their movement. Small wireless
      sensors, such as accelerometers and gyroscopes, can be utilized to provide a
      quantitative measure of the human movement for assessment. In this paper, a
      kinematics-based approach is developed to estimate human leg posture and velocity
      from wearable sensors during the performance of typical physiotherapy and
      training exercises. The proposed approach uses an extended Kalman filter to
      estimate joint angles from accelerometer and gyroscopic data and is capable of
      recovering joint angles from arbitrary 3D motion. Additional joint limit
      constraints are implemented to reduce drift, and an automated approach is
      developed for estimating and adapting the process noise during online estimation.
      The approach is validated through a user study consisting of 20 subjects
      performing knee and hip rehabilitation exercises. When compared to motion
      capture, the approach achieves an average root-mean-square error of 4.27 cm for
      unconstrained motion, with an average joint error of 6.5 degrees . The average
      root-mean-square error is 3.31 cm for sagittal planar motion, with an average
      joint error of 4.3 degrees .

PMID- 23174668
TI  - Antidepressant-like effect of trans-resveratrol in chronic stress model:
      behavioral and neurochemical evidences.
AB  - Trans-resveratrol is a phenolic compound enriched in polygonum cuspidatum and has
      diverse biological activities. There is only limited information about the
      antidepressant-like effect of trans-resveratrol. The present study investigated
      whether trans-resveratrol has antidepressant-like activity in rats exposed to
      chronic stress by using two behavioral tasks, shuttle box and sucrose preference
      tests. The monoamines (5-HT, noradrenaline and dopamine) and their metabolites as
      well as monoamine oxidase (MAO) enzyme activities in different brain regions were
      also measured. Compared to unstressed rats, those exposed to chronic stress
      paradigm showed performance deficits in the shuttle box, reduced sucrose
      preference, less weight gain and the increase in the ratio of adrenal gland to
      body weight, which were reversed by chronic treatment with trans-resveratrol (40
      and 80 mg/kg, i.g.). The neurochemical assay showed that higher dose of trans
      resveratrol (80 mg/kg) produced a marked increase of 5-HT levels in three brain
      regions, the frontal cortex, hippocampus and hypothalamus. Noradrenaline and
      dopamine levels were also increased both in the frontal cortex and striatum.
      Furthermore, chronic treatment with trans-resveratrol was found to inhibit
      monoamine oxidase-A (MAO-A) activity in all the four brain regions, particularly
      in the frontal cortex and hippocampus; while MAO-B activity was not affected.
      These findings indicate that the antidepressant-like effect of trans-resveratrol
      involves the regulation of the central serotonin and noradrenaline levels and the
      related MAO-A activities.

PMID- 23174669
TI  - Impact of emollients on the spreading properties of cosmetic products: a combined
      sensory and instrumental characterization.
AB  - This study deals with the impact of emollients on the spreading properties of
      cosmetic products using a combined sensory-instrumental approach. To that
      purpose, three esters and one silicone were selected and incorporated separately
      into an oil phase. Different cosmetic o/w emulsions were then prepared with these
      different oil phases. Both of them were analyzed by instrumental techniques and
      in vivo sensory analyses. A significant effect of the emollient used was
      established in emulsions and in oil phases as well. Concerning emulsions, results
      reveal a clear correlation between in vivo spreading evaluation and friction
      coefficient parameters measured by texture analyzer, despite a fairly low
      correlation coefficient (Pearson coefficient=-0.78). Concerning oil phases,
      characterization of spreading was done by monitoring the contact angle relaxation
      of a drop of solution after deposition on a flat PMMA surface whereas sensory
      procedure was based on spontaneous spreading of oil phases onto the skin.
      Finally, good correlations between in vivo sensory analysis and instrumental
      measurements of both oils and emulsions were found, thus promising the possible
      development of predictive tools to evaluate spreadability.

PMID- 23174670
TI  - Enabling the utilization of wool as an enzyme support: enhancing the activity and
      stability of lipase immobilized onto woolen cloth.
AB  - An improved, simple, effective and superior protocol has been developed to
      immobilize amano lipase from Pseudomonas fluorescens on woolen cloth using
      polyethyleneimine (PEI) with glutaraldehyde (GA) cross-linking. The success of
      immobilization was confirmed by FTIR and confocal laser scanning microscope
      (CLSM), the latter proving that enzyme is well distributed across the wool fiber
      surfaces throughout the cloth. Woolen cloth therefore provides a large outer and
      inner fiber surface area for immobilization with minimal mass transfer
      resistances during immobilization. The optimal protocol (GA at 0.5% and pH 6,
      lipase solution pH 6) gave an enzyme load of 46.6 mg g(-1)dry cloth with
      expressed activity of 178.3 U, 46.8% immobilization yield and 30.2% retained
      activity. Zeta potential measurements showed that PEI significantly enhanced the
      positive charge on woolen cloth and shifted the isoelectric point to
      approximately 7. Therefore at a lipase solution pH of around 6, the wool-PEI and
      lipase are oppositely charged, leading to a maximal adsorption of lipase to the
      wool surface. The immobilized lipase also had a good stability and 81% of its
      original activity was maintained after 10 runs in tributyrin emulsion hydrolysis.
      This protocol provides a significant improvement in terms of retained activity
      and lipase stability compared to previous immobilizations on wool and opens up
      the possibility of using wool as a cheap and effective lipase support material
      for continuous lipase reactions/reactors and possibly enzyme enhanced woolen
      fabrics.

PMID- 23174671
TI  - HomoTarget: a new algorithm for prediction of microRNA targets in Homo sapiens.
AB  - MiRNAs play an essential role in the networks of gene regulation by inhibiting
      the translation of target mRNAs. Several computational approaches have been
      proposed for the prediction of miRNA target-genes. Reports reveal a large
      fraction of under-predicted or falsely predicted target genes. Thus, there is an
      imperative need to develop a computational method by which the target mRNAs of
      existing miRNAs can be correctly identified. In this study, combined pattern
      recognition neural network (PRNN) and principle component analysis (PCA)
      architecture has been proposed in order to model the complicated relationship
      between miRNAs and their target mRNAs in humans. The results of several types of
      intelligent classifiers and our proposed model were compared, showing that our
      algorithm outperformed them with higher sensitivity and specificity. Using the
      recent release of the mirBase database to find potential targets of miRNAs, this
      model incorporated twelve structural, thermodynamic and positional features of
      miRNA:mRNA binding sites to select target candidates. 

PMID- 23174672
TI  - Neuroprotective effects of Cyperus rotundus on SIN-1 induced nitric oxide
      generation and protein nitration: ameliorative effect against apoptosis mediated
      neuronal cell damage.
AB  - Nitrosylation of tyrosine (3-nitro tyrosine, 3-NT) has been implicated in the
      pathophysiology of various disorders particularly neurodegenerative conditions
      and aging. Cyperus rotundus rhizome is being used as a traditional folk medicine
      to alleviate a variety of disorders including neuronal stress. The herb has
      recently found applications in food and confectionary industries also. In current
      study, we have explored the protective effects of C. rotundus rhizome extract
      (CRE) through its oxido-nitrosative and anti apoptotic mechanism to attenuate
      peroxynitrite (ONOO(-)) induced neurotoxicity using human neuroblastoma SH-SY5Y
      cells. Our results elucidate that pre-treatment of neurons with CRE ameliorates
      the mitochondrial and plasma membrane damage induced by 500 MUM SIN-1 to 80% and
      24% as evidenced by MTT and LDH assays. CRE inhibited NO generation by
      downregulating i-NOS expression. SIN-1 induced depletion of antioxidant enzyme
      status was also replenished by CRE which was confirmed by immunoblot analysis of
      SOD and CAT. The CRE pre-treatment efficiently potentiated the SIN-1 induced
      apoptotic biomarkers such as bcl-2 and caspase-3 which orchestrate the
      proteolytic damage of the cell. The ONOO(-) induced damage to cellular, nuclear
      and mitochondrial integrity was also restored by CRE. Furthermore, CRE pre
      treatment also regulated the 3-NT formation which shows the potential of plant
      extract against tyrosine nitration. Taken together, our findings suggest that CRE
      might be developed as a preventive agent against ONOO(-) induced apoptosis.

PMID- 23174674
TI  - Aiming high, but investing little.

PMID- 23174673
TI  - A Salmonella Typhi homologue of bacteriophage muramidases controls typhoid toxin
      secretion.
AB  - Unlike other Salmonella, which can infect a broad range of hosts causing self
      limiting infection, Salmonella Typhi is an exclusively human pathogen that causes
      typhoid fever, a life-threatening systemic disease. Typhoid toxin is a unique
      virulence factor of Salmonella Typhi, which is expressed when the bacteria are
      within mammalian cells. Here, we report that an N-acetyl-beta-D-muramidase
      similar to phage endolysins encoded within the same pathogenicity islet as the
      toxin is required for typhoid toxin secretion. Genetic and functional analysis of
      TtsA revealed unique amino acids at its predicted peptidoglycan-binding domain
      that are essential for protein secretion and that distinguishes this protein from
      other homologues. We propose that TtsA defines a new protein secretion mechanism
      recently evolved from the machine that mediates phage release.

PMID- 23174675
TI  - Effects of intermedin1-53 on myocardial fibrosis.
AB  - Intermedin (IMD) is a member of the calcitonin/calcitonin gene-related peptide
      (CGRP) family and has similar or more potent cardiovascular actions than
      adrenomedullin (ADM) and any other CGRP. The aim of the present work is to study
      the effects of IMD1-53 on cardiac fibroblast fibrosis in vivo and in vitro.
      Myocardial infarction model was prepared by ligating rats' left anterior
      descending coronary artery. Mesenchymal collagen contents in the left ventricle
      were accessed by Sirius-red stain. Heart functions were explored by hemodynamic
      changes. Expression of I and III type collagens, IMD1-53, receptor activity
      modifying proteins (RAMP)1/2/3, and calcitonin receptor-like receptor (CRLR) in
      left ventricle were detected by western blot analysis. Cardiac fibroblasts (CFbs)
      fibrosis was induced by treating the cells with aldosterone (ALD). CFbs
      proliferation and the hydroxyproline contents in supernatants were determined by
      3-[4,5-dimehyl-2-thiazolyl]-2,5-diphenyl-2H-tetrazolium bromide assay and enzyme
      linked immunosorbent assay. Heart function was decreased in myocardial infarction
      model rats. Expression of type I and type III collagens in infarcted zone in
      myocardial rats was higher than those in the sham-operated group. IMD1-53, RAMP,
      and CRLR in left ventricle were also up-regulated. In vitro experiment showed
      that ALD was a powerful stimulator of CFbs activation. IMD1-53 decreased ALD
      induced CFbs proliferation in a dose-dependent manner. Moreover, CGRP8-37 and
      ADM22-52 remarkably blocked the effect of IMD1-53 on ALD-induced myocardial cell
      fibrosis. IMD could be involved in the onset of cardiac fibrosis. Like ADM, IMD1
      53 exerts an antifibrotic effect on CFbs, which might be mediated by CRLR/RAMP
      complex and ADM receptor.

PMID- 23174676
TI  - Antioxidant effect of apolipoprotein A-I on high-fat diet-induced non-alcoholic
      fatty liver disease in rabbits.
AB  - Non-alcoholic fatty liver disease (NAFLD) is an increasingly recognized condition
      that encompasses a spectrum of liver abnormalities. It has been suggested that
      oxidative stress and lipid peroxidation are key pathophysiological mechanisms in
      NAFLD. Although an antioxidant effect of apolipoprotein A-I (apoA-I) has been
      reported, its influence on NAFLD has not been reported. The aim of this study was
      to determine whether apoA-I could improve the biochemical and histological
      abnormalities associated with high-fat diet-induced NAFLD through its antioxidant
      actions in rabbits. Liver damage was evaluated by hepatic coefficient, hepatic
      lipid assay, liver apparent abnormalities as well as hematoxylin-eosin staining
      of liver sections. Lipid peroxidation was assessed by measuring malondialdehyde
      (MDA) level in liver. Oxidative stress was assessed by measuring superoxide
      dismutase (SOD), glutathione peroxidase (GPx), and inducible nitric oxide
      synthase (iNOS) activities in serum and liver. Also, the mRNA expressions levels
      of SOD, GPx, and catalase (CAT) were determined by real-time quantitative
      polymerase chain reaction method. The results showed that apoA-I (20 or 40
      mg/kg/w) was effective in reducing hepatic steatosis, inflammation, hepatic
      coefficient, and liver total cholesterol, triglyceride, low-density lipoprotein
      cholesterol, and MDA levels in high-fat diet rabbits. In addition, apoA-I
      increased SOD and GPx activities while reducing iNOS activity in serum and liver.
      Moreover, apoA-I significantly increased the mRNA expression levels of SOD, GPx,
      and CAT in liver. This study showed that apoA-I exerted protective effects
      against fatty liver disease in rabbits induced by a high-fat diet, possibly
      through its antioxidant actions.

PMID- 23174677
TI  - December reflections.

PMID- 23174678
TI  - Achieving our goals: strengthen relationships.

PMID- 23174679
TI  - Pin it to win it: using pinterest to promote your niche services.

PMID- 23174680
TI  - The Health Information Technology for Economic and Clinical Health (HITECH) Act
      and Nutrition Inclusion in Medicare/Medicaid Electronic Health Records:
      leveraging policy to support nutrition care.

PMID- 23174681
TI  - Nutrition for pregnant women who have cystic fibrosis.

PMID- 23174682
TI  - A longitudinal study of food insecurity on obesity in preschool children.
AB  - BACKGROUND: Obesity and its co-occurrence with household food insecurity among
      low-income families is a public health concern, particularly because both are
      associated with later adverse health consequences. OBJECTIVE: Our aim was to
      examine the relationship between household food insecurity with and without
      hunger in infancy and later childhood with weight status at 2 to 5 years. DESIGN:
      This longitudinal study uses household food-security status, weight, and height
      data collected at the first infancy and last child (2 to 5 years) Special
      Supplemental Nutrition Program for Women, Infants, and Children visits. Household
      food security was based on parent/caretaker responses to a four-question subscale
      of the 18-item Core Food Security Module. Obesity was defined as sex-specific
      body mass index for age >= 95th percentile. PARTICIPANTS/SETTING: A diverse
      (58.6% non-white) low-income sample of 28,353 children participating in the
      Massachusetts Special Supplemental Nutrition Program for Women, Infants, and
      Children (2001-2006); 24.9% of infants and 23.1% of children lived in food
      insecure households and 17.1% were obese at their last child visit. STATISTICAL
      ANALYSIS: Multivariate logistic regression analyses assessed the association
      between household food-security status during the infant and child visits, and
      risk of preschool obesity, while controlling for child race/Hispanic ethnicity,
      sex, child and household size, maternal age, education, and prepregnancy weight.
      Interactions between these covariates and household food-security status were
      also examined. In cases of multiple comparisons, a Bonferroni correction was
      applied. RESULTS: Persistent household food insecurity without hunger was
      associated with 22% greater odds of child obesity (odds ratio=1.22; 95% CI 1.06
      to 1.41) compared with those persistently food secure (P<0.05). Maternal
      prepregnancy weight status modified this association with children of underweight
      (adjusted odds ratio=3.22; 95% CI 1.70 to 6.11; P=0.003) or overweight/obese
      (adjusted odds ratio=1.34; 95% CI 1.11 to 1.62; P=0.03) mothers experiencing
      greater odds of child obesity with persistent household food insecurity without
      hunger compared with those with persistent household food security. CONCLUSIONS:
      These results suggest that persistent household food insecurity without hunger is
      prospectively related to child obesity, but that these associations depend on
      maternal weight status. Vulnerable groups should be targeted for early
      interventions to prevent overweight and obesity later in life.

PMID- 23174683
TI  - Predicting successful introduction of novel fruit to preschool children.
AB  - BACKGROUND: Few children eat sufficient fruits and vegetables despite their
      established health benefits. The feeding practices used by parents when
      introducing novel foods to their children, and their efficacy, require further
      investigation. OBJECTIVE: We aimed to establish which feeding strategies parents
      commonly use when introducing a novel fruit to their preschool-aged children and
      assess the effectiveness of these feeding strategies on children's willingness to
      try a novel fruit. DESIGN: Correlational design. PARTICIPANTS/SETTING: Twenty
      five parents and their children aged 2 to 4 years attended our laboratory and
      consumed a standardized lunch, including a novel fruit. Interactions between
      parent and child were recorded and coded. STATISTICAL ANALYSES PERFORMED:
      Pearson's correlations and multiple linear regression analyses. RESULTS: The
      frequency with which children swallowed and enjoyed the novel fruit, and the
      frequency of taste exposures to the novel fruit during the meal, were positively
      correlated with parental use of physical prompting and rewarding/bargaining.
      Earlier introduction of solids was related to higher frequency of child
      acceptance behaviors. The child's age at introduction of solids and the number of
      physical prompts displayed by parents significantly predicted the frequency of
      swallowing and enjoying the novel fruit. Age of introduction to solids and
      parental use of rewards/bargaining significantly predicted the frequency of taste
      exposures. CONCLUSIONS: Prompting a child to eat and using rewards or bargains
      during a positive mealtime interaction can help to overcome barriers to novel
      fruit consumption. Early introduction of solids is also associated with greater
      willingness to consume a novel fruit.

PMID- 23174684
TI  - A novel approach to selecting and weighting nutrients for nutrient profiling of
      foods and diets.
AB  - BACKGROUND: Nutrient profiling of foods is the science of ranking or classifying
      foods based on their nutrient composition. Most profiling systems use similar
      weighting factors across nutrients due to lack of scientific evidence to assign
      levels of importance to nutrients. OBJECTIVE: Our aim was to use a statistical
      approach to determine the nutrients that best explain variation in Healthy Eating
      Index (HEI) scores and to obtain beta-coefficients for the nutrients for use as
      weighting factors for a nutrient-profiling algorithm. DESIGN: We used a cross
      sectional analysis of nutrient intakes and HEI scores. PARTICIPANTS: Our subjects
      included 16,587 individuals from the National Health and Nutrition Examination
      Survey 2005-2008 who were 2 years of age or older and not pregnant. MAIN OUTCOME
      MEASURE: Our main outcome measure was variation (R(2)) in HEI scores. STATISTICAL
      ANALYSES: Linear regression analyses were conducted with HEI scores as the
      dependent variable and all possible combinations of 16 nutrients of interest as
      independent variables, with covariates age, sex, and ethnicity. The analyses
      identified the best 1-nutrient variable model (with the highest R(2)), the best 2
      nutrient variable model, and up to the best 16-nutrient variable model. RESULTS:
      The model with 8 nutrients explained 65% of the variance in HEI scores, similar
      to the models with 9 to 16 nutrients, but substantially higher than previous
      algorithms reported in the literature. The model contained five nutrients with
      positive beta-coefficients (ie, protein, fiber, calcium, unsaturated fat, and
      vitamin C) and three nutrients with negative coefficients (ie, saturated fat,
      sodium, and added sugar). beta-coefficients from the model were used as weighting
      factors to create an algorithm that generated a weighted nutrient density score
      representing the overall nutritional quality of a food. CONCLUSIONS: The weighted
      nutrient density score can be easily calculated and is useful for describing the
      overall nutrient quality of both foods and diets.

PMID- 23174685
TI  - Air displacement plethysmography, dual-energy X-ray absorptiometry, and total
      body water to evaluate body composition in preschool-age children.
AB  - Anthropometrics and body mass index are only proxies in the evaluation of
      adiposity in the pediatric population. Air displacement plethysmography
      technology was not available for children aged 6 months to 9 years until
      recently. Our study was designed to test the precision of air displacement
      plethysmography (ADP) in measuring body fat mass in children at ages 3 to 5 years
      compared with a criterion method, deuterium oxide dilution (D(2)O), which
      estimates total body water and a commonly used methodology, dual-energy x-ray
      absorptiometry (DXA). A prospective, cross-sectional cohort of 66 healthy
      children (35 girls) was recruited in the central Arkansas region between 2007 and
      2009. Weight and height were obtained using standardized procedures. Fat mass (%)
      was measured using ADP, DXA, and D(2)O. Concordance correlation coefficient and
      Bland-Altman plots were used to investigate the precision of the ADP techniques
      against D(2)O and DXA in children at ages 3 to 5 years. ADP concordance
      correlation coefficient for fat mass was weak (0.179) when compared with D(2)O.
      Bland-Altman plots revealed a low accuracy and large scatter of ADP fat mass (%)
      results (mean=-2.5, 95% CI -20.3 to 15.4) compared with D(2)O. DXA fat mass (%)
      results were more consistent although DXA systematically overestimated fat mass
      by 4% to 5% compared with D(2)O. Compared with D(2)O, ADP does not accurately
      assess percent fat mass in children aged 3 to 5 years. Thus, D(2)O, DXA, or
      quantitative nuclear magnetic resonance may be considered better options for
      assessing fat mass in young children.

PMID- 23174686
TI  - Fat-free mass depletion and inflammation in patients with bronchiectasis.
AB  - Fat-free mass depletion has been related to increased inflammatory activity and
      to increased morbidity and mortality in chronic respiratory diseases. The aims of
      our study were to determine the nutritional status and serum levels of
      adipocytokines and inflammatory cytokines in patients with bronchiectasis of any
      etiology and their relation with respiratory parameters. A cross-sectional study
      was designed that included patients aged >14 years with diagnostic criteria for
      bronchiectasis. Anthropometric parameters; a diet questionnaire; hand grip
      dynamometry; levels of leptin, adiponectin, interleukin-6 (IL-6), tumor necrosis
      factor-alpha, and ultrasensitive C-reactive protein; as well as respiratory
      parameters (ie, clinical, radiologic, and spirometric values) were assessed.
      Ninety-three clinically stable patients were recruited, 43 with cystic fibrosis,
      31 with noncystic fibrosis bronchiectasis, and 19 with cystic fibrosis
      transmembrane conductance regulator-related bronchiectasis. Fat-free mass
      depletion was present in 31% of patients, with no differences according to the
      etiology of the bronchiectasis. Correlations were found between inflammatory
      cytokines (ie, IL-6) and exacerbations, bronchorrea, forced expiratory volume in
      1 second, and Bhalla score. Patients with worse respiratory disease severity,
      malnutrition, and diabetes had significantly higher levels of IL-6. Adiponectin
      correlated significantly and positively with fat mass and fat mass index and
      negatively with fat-free mass, fat-free mass index, and hand dynamometry. Leptin
      correlated positively with body mass index, fat mass and fat mass index, and
      negatively with fat-free mass, fat-free mass index, and dynamometry. Patients
      with bronchiectasis present a high percentage of fat-free mass depletion,
      independent of the etiology of the disease. The levels of inflammatory cytokines
      (especially IL-6) may be useful markers of disease severity. Adiponectin levels
      were higher in patients with fat-free mass depletion.

PMID- 23174687
TI  - Maternal misconceptions of weight status among Nepean adolescents.
AB  - Adolescence is characterized by rapid physical growth and sexual maturation.
      These changes may alter parents' beliefs about their adolescent's weight status.
      This study aimed to examine the changes between early and mid-adolescence in: (a)
      the accuracy of maternal perception regarding her adolescent's weight status, (b)
      the degree of maternal concern about her adolescent's weight status, and (c) the
      predictors of maternal misclassification of adolescent overweight as average
      weight. A secondary analysis of the longitudinal Nepean Study data was conducted.
      Participants were Australian, free-living 13-year-olds in 2002-2003 (n=347)
      followed up at age 15 years (n=279) and their mothers. Participants' body mass
      index (BMI) status (overweight, normal, or underweight) was calculated from
      measured height and weight. Maternal perceptions and concerns about adolescent's
      weight status were determined by items adapted from the Child Feeding
      Questionnaire. Sex-adjusted binary logistic regression models assessed potential
      predictors of maternal misclassification of adolescent overweight. Data were
      available on 224 adolescent-mother dyads. Approximately one fourth of mothers
      misclassified their adolescent's weight status, but this varied across groups
      (age 13 years [%]; age 15 years [%], respectively) underweight (75%; 70%),
      overweight (54%; 59%), and normal weight (12%; 9%). The endpoint data show that
      between 13 and 15 years of age, maternal concern regarding their adolescent's
      weight decreased in all weight-status groups. Predictors of maternal
      misclassification of adolescent overweight were adolescent BMI z score, recent
      weight-management practices, weight history, sex, and maternal concern regarding
      her adolescent's weight. These results reinforce the need for strategies in
      primary care that are implemented throughout adolescence to improve maternal
      awareness of childhood overweight.

PMID- 23174688
TI  - Household income disparities in fruit and vegetable consumption by state and
      territory: results of the 2009 Behavioral Risk Factor Surveillance System.
AB  - Few studies take into account the influence of family size on household resources
      when assessing income disparities in fruit and vegetable (F/V) consumption.
      Poverty income ratio (PIR) is a measure that utilizes both reported income and
      household size. We sought to examine state-specific disparities in meeting
      Healthy People 2010 objectives for F/V consumption by percent PIR. This analysis
      included 353,005 adults in 54 states and territories reporting data to the 2009
      Behavioral Risk Factor Surveillance System in the United States. Percent PIR was
      calculated using the midpoint of self-reported income range and family size. The
      prevalences consuming at least two fruits and at least three vegetables per day
      were examined by percent PIR (<130% [greatest poverty], 130% to <200%, 200% to
      <400%, and >= 400% [least poverty]). The percent of adults consuming vegetables
      at least three times daily was significantly lower (21.3%) among those living at
      greatest poverty (<130% PIR) compared with 30.7% among those with least poverty
      (>= 400% PIR). Daily consumption of vegetables at least three times was
      significantly lower among those with greatest poverty in a majority of states and
      territories surveyed (43 of 54). The overall percent of adults consuming fruits
      at least 2 times daily was also lower among those living at greatest vs least
      poverty, but the difference was smaller (32.0% vs 34.2%), with 14 states
      reporting a difference that was significantly lower among those with greatest
      poverty. Our study revealed that in 2009 a significantly lower proportion of US
      adults living at greatest poverty consumed fruits at least two times daily or
      vegetables at least three times daily compared with those with the least poverty,
      with greater disparity in vegetable intake. Policy and environmental strategies
      for increased affordability, access, availability, and point-of-decision
      information are approaches that may help disparate households purchase and
      consume F/V.

PMID- 23174689
TI  - Fruit, vegetable, and antioxidant intakes are lower in older adults with
      depression.
AB  - Studies have shown an association between depression and both antioxidant levels
      and oxidant stress, but generally have not included intakes of antioxidants and
      antioxidant-rich fruits and vegetables. This study examined the cross-sectional
      associations between clinically diagnosed depression and intakes of antioxidants,
      fruits, and vegetables in a cohort of older adults. Antioxidant, fruit, and
      vegetable intakes were assessed in 278 elderly participants (144 with depression,
      134 without depression) using a Block 1998 food frequency questionnaire that was
      administered between 1999 and 2007. All participants were aged 60 years or older.
      Vitamin C, lutein, and beta cryptoxanthin intakes were significantly lower among
      individuals with depression than in comparison participants (P<0.05). In
      addition, fruit and vegetable consumption, a primary determinant of antioxidant
      intake, was lower in individuals with depression. In multivariable models
      controlling for age, sex, education, vascular comorbidity score, body mass index,
      total dietary fat, and alcohol; vitamin C, beta cryptoxanthin, fruits, and
      vegetables remained significant. Antioxidants from dietary supplements were not
      associated with depression. Antioxidant, fruit, and vegetable intakes were lower
      in individuals with late-life depression than in comparison participants. These
      associations may partially explain the elevated risk of cardiovascular disease
      among older individuals with depression. In addition, these findings point to the
      importance of antioxidant food sources rather than dietary supplements.

PMID- 23174690
TI  - Nutrition informatics competencies across all levels of practice: a national
      Delphi study.

PMID- 23174691
TI  - Is there a recommended target range for blood glucose for the type 1 diabetic
      endurance athlete?

PMID- 23174692
TI  - Why REM sleep? Clues beyond the laboratory in a more challenging world.
AB  - REM sleep (REM) seems more likely to prepare for ensuing wakefulness rather than
      provides recovery from prior wakefulness, as happens with 'deeper' nonREM. Many
      of REM's characteristics are 'wake-like' (unlike nonREM), including several
      common to feeding. These, with recent findings outside sleep, provide
      perspectives on REM beyond those from the laboratory. REM can interchange with a
      wakefulness involving motor output, indicating that REM's atonia is integral to
      its function. Wakefulness for 'wild' mammals largely comprises exploration; a
      complex opportunistic behaviour mostly for foraging, involving: curiosity,
      minimising risks, (emotional) coping, navigation, when (including circadian
      timing) to investigate new destinations; all linked to 'purposeful, goal directed
      movement'. REM reflects these adaptive behaviours (including epigenesis), masked
      in laboratories having constrained, safe, unchanging, unchallenging, featureless,
      exploration-free environments with ad lib food. Similarly masked may be REM's
      functions for today's humans living safe, routine lives, with easy food
      accessibility. In these respects animal and human REM studies are not
      sufficiently 'ecological'.

PMID- 23174693
TI  - Deficient safety learning characterizes high trait anxious individuals.
AB  - Trait anxiety is a well-established risk factor for developing anxiety disorders,
      but evidence for abnormal associative fear learning in high trait anxious (HTA)
      individuals is inconclusive. In part, this may due to limitations in the scope
      and measures used to assess fear learning. The current study therefore assessed
      fear learning across multiple response domains and multiple test phases in a two
      day discriminative fear-conditioning paradigm. We tested whether trait anxiety is
      associated with deficient safety learning, by comparing HTA individuals (N=20)
      and healthy Controls (N=22). HTA participants showed stronger fear on the startle
      response and distress ratings to the safety (CS(-)) but not to the threat
      stimulus (CS(+)) during acquisition, along with impaired extinction and re
      extinction. Trait anxiety did not affect skin conductance responses and effects
      on UCS-expectancy were limited. We conclude that high trait anxiety may be
      characterized by deficient safety learning which in turn may promote persistent
      and generalized fear responses.

PMID- 23174694
TI  - Translation: that's the question.

PMID- 23174695
TI  - Aversive learning increases sensory detection sensitivity.
AB  - Increased sensitivity to specific cues in the environment is common in anxiety
      disorders. This increase in sensory processing can emerge through attention
      processes that enhance discrimination of a cue from other cues as well as through
      augmented senses that reduce the absolute intensity of sensory stimulation needed
      for detection. Whereas it has been established that aversive conditioning can
      enhance odor quality discrimination, it is not known whether it also changes the
      absolute threshold at which an odor can be detected. In two separate experiments,
      we paired one odor of an indistinguishable odor pair with an aversive outcome
      using a classical conditioning paradigm. Ability to discriminate and to detect
      the paired odor was assessed before and after conditioning. The results
      demonstrate that aversive conditioning increases absolute sensory sensitivity to
      a predictive odor cue in an odor-specific manner, rendering the conditioned odor
      detectable at a significantly lower (20%) absolute concentration. As animal
      research has found long-lasting change in behavior and neural signaling resulting
      from conditioning, absolute threshold was also tested eight weeks later.
      Detection threshold had returned to baseline level at the eight week follow-up
      session suggesting that the change in detection threshold was mediated by a
      transient reorganization. Taken together, we can for the first time demonstrate
      that increasing the biological salience of a stimulus augments the individual's
      absolute sensitivity in a stimulus-specific manner outside conscious awareness.
      These findings provide a unique framework for understanding sensory mechanisms in
      anxiety disorders as well as further our understanding of mechanisms underlying
      classical conditioning.

PMID- 23174696
TI  - Malathion exposure induces the endocrine disruption and growth retardation in the
      catfish, Clarias batrachus (Linn.).
AB  - Many hormones are known for their role in the regulation of metabolic activities
      and somatic growth in fishes. The present study deals with the effects of
      malathion (an organophosphorous pesticide) on the levels of metabolic hormones
      that are responsible for promotion of somatic and ovarian growth of the
      freshwater catfish, Clarias batrachus. Malathion treatment for thirty days
      drastically reduced the food intake and body weight of fish. These fish also
      exhibited a great avoidance to food. Exposure of catfish to malathion reduced the
      levels of thyroxine (T(4)), triiodothyronine (T(3)), growth hormone (GH), insulin
      like growth factor-I (IGF-I), testosterone (T) and estradiol-17beta (E(2)) in a
      dose dependent manner during all the studied reproductive phases, in general,
      except that malathion increased the level of GH during the quiescence phase.
      Significant reduction in muscle and hepatic protein content also occurred in the
      malathion-treated fish. Malathion exposure induced lipolysis too in the liver and
      muscle. The results thus support that malathion treatment disrupts the endocrine
      functions and the olfactory sensation responsible for food intake and gustatory
      feeding behavior, which ultimately leads to retardation of fish growth.

PMID- 23174697
TI  - Seasonal variations in plasma vitellogenin and sex steroids in male and female
      Eastern Box Turtles, Terrapene carolina carolina.
AB  - The Eastern Box Turtle (Terrapene carolina carolina) is a widespread species that
      has recently experienced precipitous declines throughout its range. Although many
      studies have documented aspects of reproduction in box turtles, reproductive
      physiology of free-ranging animals is unknown and can be crucial in this species'
      recovery. Over a two-year period, we measured reproductive parameters,
      (vitellogenin [Vtg], estradiol-17beta [E2], and total testosterone [TT]), in
      plasma of 116 free-ranging Eastern Box Turtles across their active season. We
      found similar seasonal variations of Vtg and E2 within females. Mid-season,
      females showed a sharp peak in E2 that correlates with the putative beginning of
      the ovarian cycle. Individual females lacking these expected peaks of both Vtg
      and E2 suggest that some female T. c. carolina may not reproduce annually.
      Females typically expressed undetectable levels of TT, yet there was a small peak
      in TT early in the active season. Male Eastern Box Turtles exhibited a dual peak
      in TT. Elevated TT in males was significantly associated with observed sexual
      behaviors and smaller home ranges. Body condition had no effect on the
      concentration of TT or E2 in either sex. This is the first study to (1) document
      Vtg and sex steroid hormones in free-ranging animals of this genus, and (2)
      relate those metrics to individuals, the population, the purported annual cycle,
      and to other chelonian species.

PMID- 23174698
TI  - Participation of cAMP-dependent protein kinase and MAP kinase pathways during
      Anabas testudineus oocyte maturation.
AB  - Possible involvement of cyclic nucleotide dependent protein kinase (PKA) and MAP
      kinase (MAPK) pathways during oocyte maturation in Anabas testudineus was
      investigated. Pre-incubation with phosphodiesterase (PDE) inhibitor, 3-isobutyl-1
      methylxanthine (IBMX), inhibited 17alpha, 20beta-DHP-induced GVBD dose
      dependently. PKA inhibitor, H89 could induce resumption of meiosis independent of
      17alpha, 20beta-DHP, in dose and duration dependent manner. The maximum response
      was obtained with the dose of 10 MUM of H89 and 95% of cells underwent GVBD
      within 18 h. Moreover, stimulation with 17alpha, 20beta-DHP inhibited endogenous
      PKA activity significantly within first hour and this effect was attenuated by
      PDE inhibitor IBMX at all time points. The pattern of PKA inhibition corresponded
      well with kinetics of histone H1 kinase activation and p34cdc2 phosphorylation.
      These results suggest physiological relevance of cAMP/PKA signaling in perch
      oocytes undergoing G2/M transition. MAPK was demonstrated as two distinct
      isoforms (ERK1 and ERK2) which resolved in the range of 42-44 kDa in immunoblot.
      Though total protein content did not show significant variation, H89 stimulation
      was able to stimulate phosphorylation of ERK1/2 from 5h onwards and the strongest
      response was observed between 10 and 18 h. MEK inhibitor, U0126 completely
      blocked PKA inhibition induced MAPK activation and GVBD. In addition, inhibition
      of endogenous PKA by a more selective peptide inhibitor [PKI-(6-22)-amide] was
      sufficient to resume GVBD and MAPK activation in intact perch oocytes. Also,
      significant ERK1/2 phosphorylation could be stimulated in cell-free extracts of
      perch oocytes supplemented with PKI-(6-22)-amide. The results suggest an
      interaction between cAMP/PKA and MAPK pathways in mediating meiosis resumption in
      perch oocyte.

PMID- 23174699
TI  - Immunosurveillance against cancer-associated hyperploidy.

PMID- 23174700
TI  - Lubricin and smooth muscle alpha-actin-containing myofibroblasts in the
      pseudomembranes around loose hip and knee prostheses.
AB  - The objective was to evaluate the presence and distribution of the lubricating
      and anti-adhesion glycoprotein lubricin and cells containing the contractile
      isoform smooth muscle alpha-actin (SMA) in pseudomembranes around loose hip
      prostheses. Periprosthetic tissue was obtained at revision arthroplasty of eight
      aseptic, loose hip implants, and for comparison three loose knee prostheses.
      Immunohistochemical analysis was performed in 3 zones: zone 1, within 300MUm of
      the edge of the implant-tissue interface; zone 2, between zones 1 and 3; zone 3,
      within 300MUm of the resected/trimmed edge. The presence of lubricin was
      extensive in all samples: (1) as a discrete layer at the implant-tissue
      interface; (2) within the extracellular matrix (ECM); (3) intracellularly. There
      was significantly more high grade (>50%) lubricin surface staining at the implant
      tissue interface compared with the resected edge. While there was also a
      significant effect of location of high grade ECM lubricin staining, there was no
      significant effect of implant type (i.e. hip versus knee). All but two hip
      pseudomembrane samples showed the presence of many SMA-containing cells. There
      was a significant effect of location on the number of SMA-expressing cells, but
      not of implant type. These findings might explain why the management of loose
      prosthesis is so challenging.

PMID- 23174701
TI  - Creatine pretreatment prevents birth asphyxia-induced injury of the newborn spiny
      mouse kidney.
AB  - BACKGROUND: Acute kidney injury (AKI) is a major complication for infants
      following an asphyxic insult at birth. We aimed to determine if kidney structure
      and function were affected in an animal model of birth asphyxia and if maternal
      dietary creatine supplementation could provide an energy reserve to the fetal
      kidney, maintaining cellular respiration during asphyxia and preventing AKI.
      METHODS: Pregnant spiny mice were maintained on normal chow or chow supplemented
      with creatine from day 20 gestation. On day 38 (term ~39 d), pups were delivered
      by cesarean section (c-section) or subjected to intrauterine asphyxia. Twenty
      four hours after insult, kidneys were collected for histological or molecular
      analysis. Urine and plasma were also collected for biochemical analysis. RESULTS:
      AKI was evident at 24 h after birth asphyxia, with a higher incidence of shrunken
      glomeruli (P < 0.02), disturbance to tubular arrangement, tubular dilatation, a
      twofold increase (P < 0.02) in expression of Ngal (early marker of kidney
      injury), and decreased expression of the podocyte differentiation marker nephrin.
      Maternal creatine supplementation prevented the glomerular and tubular
      abnormalities observed in the kidney at 24 h and the increased expression of
      Ngal. CONCLUSION: Maternal creatine supplementation may prove useful in
      ameliorating kidney injury associated with birth asphyxia.

PMID- 23174702
TI  - Longitudinal diffusion tensor and manganese-enhanced MRI detect delayed cerebral
      gray and white matter injury after hypoxia-ischemia and hyperoxia.
AB  - BACKGROUND: Hypoxia-ischemia (HI) induces delayed inflammation and long-term gray
      and white matter brain injury that may be altered by hyperoxia. METHODS: HI and 2
      h of hyperoxia (100% O2) or room air (21% O2) in 7-d-old (P7) rats were studied
      by magnetic resonance imaging at 7 Tesla during 42 d: apparent diffusion
      coefficient (ADC) maps on day 1; T(1)-weighted manganese-enhanced images on day
      7; diffusion tensor images on days 21 and 42; and T2 maps at all time points.
      RESULTS: The long-term brain tissue destruction on T2 maps was more severe in
      HI+hyperoxia than HI+room air. ADC was lower in HI+hyperoxia vs. HI+room air and
      sham and was correlated with long-term outcome. Manganese enhancement indicating
      inflammation was seen in both the groups along with more microglial activation in
      HI+hyperoxia on day 7. Fractional anisotropy (FA) in corpus callosum was lower
      and radial diffusivity was higher in HI+hyperoxia than that in HI+room air and
      sham on day 21. From day 21 to day 42, FA and radial diffusivity in HI+hyperoxia
      were unchanged, whereas in HI+room air, FA increased and radial diffusivity
      decreased to values similar to sham. CONCLUSION: Hyperoxia caused a more severe
      tissue destruction, delayed irreversible white matter injury, and increased
      inflammatory response resulting in a worsening in the trajectory of injury after
      HI in developing gray and white matter.

PMID- 23174703
TI  - Development of an animal model of nephrocalcinosis via selective dietary sodium
      and chloride depletion.
AB  - BACKGROUND: Nephrocalcinosis (NC) is an important clinical problem seen in
      critically ill preterm neonates treated with loop diuretics. No reliable animal
      models are available to study the pathogenesis of NC in preterm infants. The
      purpose of this study was to develop a reproducible and clinically relevant
      animal model of NC for these patients and to explore the impact of extracellular
      fluid (ECF) volume contraction induced by sodium and chloride depletion in this
      process. METHODS: Three-week-old weanling Sprague-Dawley rats were fed diets
      deficient in either chloride or sodium or both. A subgroup of rats from each
      dietary group was injected daily with furosemide (40 mg/kg i.p.). RESULTS: Rats
      fed a control diet, with or without furosemide, or a chloride-depleted diet
      alone, did not develop NC. By contrast, 50% of the rats injected with furosemide
      and fed the chloride-depleted diet developed NC. Moreover, 94% of the rats fed
      the combined sodium- and chloride-depleted diet developed NC, independently of
      furosemide use. NC was associated with the development of severe ECF volume
      contraction; hypochloremic, hypokalemic, metabolic alkalosis; increased
      phosphaturia; and growth retardation. CONCLUSION: Severe ECF volume contraction
      induced by chronic sodium and chloride depletion appears to play an important
      role in the pathogenesis of NC.

PMID- 23174704
TI  - Plasma lipid levels and body weight altered by intrauterine growth restriction
      and postnatal fructose diet in adult rats.
AB  - BACKGROUND: Intrauterine growth restriction (IUGR) is known to affect the risk of
      adult diseases. Consumption of lipogenic fructose is increasing, and it is used
      as an enhancer of metabolic syndrome in rat experiments. The effects of IUGR,
      postnatal fructose diet, and their interaction on the lipid profile and adiposity
      were studied in adult rats. METHODS: IUGR was induced by providing pregnant rats
      with 50% of daily food intake. From 1 mo onward, half of the offspring received a
      fructose-rich diet and were then followed to the age of 1 and 6 mo, when plasma
      lipid, glucose, and insulin levels were measured. The adipose tissue was
      visualized by magnetic resonance imaging at the age of 6 mo. RESULTS: IUGR and
      fructose diet decreased body weight in adult rats. IUGR increased low-density
      lipoprotein cholesterol in 6-mo-old rats. The fructose diet evoked
      hypertriglyceridemia and hyperinsulinemia in both the sexes and decreased fasting
      glucose levels in female rats. Postnatal fructose diet increased lipid content
      percentage in the retroperitoneal and intra-abdominal adipose tissues in male
      rats. Interactions between IUGR and postnatal fructose diet were observed in
      adult weight in males. CONCLUSION: These results demonstrate the importance of
      IUGR and fructose diet in adverse changes in lipid and glucose metabolism.

PMID- 23174705
TI  - Systematic characterization of amplitude-integrated EEG signals for monitoring
      the preterm brain.
AB  - BACKGROUND: In preterm infants, the amplitude-integrated electroencephalogram
      (aEEG) is not established in clinical routine. The aim of this study was to
      derive normative data on aEEG parameters by means of longitudinal
      characterization and to evaluate the impact of gestational age (GA), postnatal
      age (PNA), postmenstrual age, sedation, and patent ductus arteriosus (PDA).
      METHODS: Recordings from 61 infants with GA 28-31 weeks were obtained during the
      first 72 h, then weekly until the age of 4 wk. Infants were divided into three
      groups: (i) no sedation, no PDA, (ii) sedation, no PDA, and (iii) sedation, PDA.
      Assessed parameters included background activity, cycling, amplitude, and log
      ratio of the maximum/minimum amplitude. RESULTS: GA and PNA had a significant
      impact within 72 h. Sedation modified aEEG, and presence of PDA was associated
      with reduced aEEG scores within 72 h. The log ratio of the amplitude correlated
      with GA but was unaffected by sedation and PDA. CONCLUSION: Evaluation of
      electrocortical background activity within the first postnatal hours and
      longitudinally over days and weeks is important to better understand the
      postnatal factors impacting cerebral function in preterm infants. There is a need
      to agree on definitions and a standardized reporting system in order to permit
      comparisons between studies and establish aEEG as a method for routine monitoring
      of preterm infants.

PMID- 23174706
TI  - [Follow-up of HIV-infected children receiving antiretroviral therapy in a rural
      area of Togo].
AB  - OBJECTIVE: To evaluate the monitoring of HIV-infected children receiving
      antiretroviral therapy in rural areas of Togo and the effectiveness of the
      treatment. METHODS: This retrospective descriptive study, conducted at the Luis
      Scrosospi Center in Kouve from 15 November, 2008, through 14 November, 2009,
      examined the records of children who had been receiving antiretroviral therapy
      for at least 6 months. RESULTS: We studied the records of 55 children. The sex
      ratio was 0.9, and the primary opportunistic infections were respiratory
      infections and malaria. At treatment initiation, their average age was 6 years
      and 3 months, the average CD4 T cell count 358/mm(3), and the mean weight 12.9
      kg. The hemoglobin level was less than 8 g/dL in 31%. All children received a
      nutritional kit monthly. The antiretroviral therapy for 52 children was a
      combination of stavudine, lamivudine, and nevirapine. The adherence rate during
      the first 12 months was 80% (44/55 children). The mean weight gain was 860 g
      (below -3SD) at 3 months, 1,550 g (between -3SD and -2SD) at 6 months, and 1 270
      g (between -2SD and -1SD) at 12 months of treatment. The severe acute
      malnutrition rate fell from 60% at treatment initiation to 56% at 3 months, 47%
      at 6 months, and 25% at 12 months. Also after 12 months, the CD4 T cell count had
      risen in 60% of the children. The main side effects were peripheral neuropathy
      (29%) and headaches (18%). Eight children died (14%) during the follow-up.
      CONCLUSION: Monitoring of HIV-infected children on antiretroviral therapy is
      possible in Togo's rural areas and should be encouraged for it will help to
      achieve the Millennium Development Goals.

PMID- 23174707
TI  - The effect of platelet-rich plasma on patterns of gene expression in a dog model
      of anterior cruciate ligament reconstruction.
AB  - BACKGROUND: Autologous platelet-rich plasma (PRP) has been investigated as a
      potential promoter of tendon healing and has an enhancing effect on the anterior
      cruciate ligament (ACL) graft maturation process. However, the influence of PRP
      on the synthesis and degradation of the extracellular matrix during the ACL graft
      remodeling process has never been investigated. MATERIALS AND METHODS: Healthy
      and mature beagle dogs were randomly assigned to one of four groups: in group I
      (PRP group), ACL grafts were treated with PRP; in group II (control group), ACL
      grafts were treated with saline; in group III (sham group), only the knee joints
      were exposed; in group IV (normal control group), no surgery was performed to the
      knees. Ligament tissue was dissected at 2, 6, and 12 wk after surgery, and real
      time PCR was performed using primers for growth factor-beta1 (TGF-beta1),
      collagen type1A1 (COL1Al), collagen type3A1 (COL3A1), decorin, biglycan, matrix
      metalloproteinase-1 (MMP-1), matrix metalloproteinase-13 (MMP-13), and tissue
      inhibitor of metalloproteinase-1 (TIMP-1). RESULT: In group I, the messenger RNA
      (mRNA) levels of collagen type 1A1, biglycan, and MMP-1 all increased 2, 6, and
      12 wk after surgery, compared with group II (P < 0.05). At 2 and 6 wk after
      surgery, increased levels of COL3A1, MMP-1, and MMP-13 mRNA were also detected in
      group I (P < 0.05). Increased levels of TGF-beta1 mRNA was observed at 6 and 12
      wk in group I after surgery (P < 0.05). CONCLUSIONS: During the graft remodeling
      process, we observed a time-dependent change of gene expression following ACL
      reconstruction surgery. Furthermore, our results demonstrate that PRP alters the
      expression of some target genes at certain time points, especially during the
      early stages of graft remodeling, which might explain the enhancing effect of PRP
      on the ACL graft maturation process.

PMID- 23174708
TI  - Risk factors and outcomes of Candida krusei bloodstream infection: a matched,
      case-control study.
AB  - OBJECTIVES: To investigate the risk factors and outcomes associated with Candida
      krusei bloodstream. METHODS: We performed a case control study of patients with
      C. krusei bloodstream infection at the University of Pennsylvania from 1982 to
      2010. Controls were without candidemia, and matched to cases on duration of
      hospitalization and underlying disease. RESULTS: We enrolled 34 cases and 114
      matched controls. Most subjects (62%) had hematologic malignancies. In the
      multivariate model, including a priori the duration of fluconazole use (OR 1.06;
      95% CI 1.00, 1.11) and days of neutropenia (OR 1.01; 95% CI 0.98, 1.13), risk
      factors associated with C. krusei bloodstream infection were splenectomy (OR
      11.66; 95% CI 1.04, 130.64), and exposure to antimicrobials with anaerobic
      activity (OR 5.74; 95% CI 1.76, 18.67). Outcomes of infected patients were poor.
      Only 32% of case patients survived to hospital discharge, compared to 89% of
      controls. For 48% death was attributed to C. krusei infection. CONCLUSIONS: C.
      krusei bloodstream infection occurs most commonly in neutropenic patients with
      hematologic malignancy. The association with prior fluconazole exposure is less
      marked than previously described. Splenectomy and the receipt of antimicrobials
      with anaerobic activity are significant risk factors. The outcome of infected
      patients remains poor, despite appropriate antifungal therapy.

PMID- 23174709
TI  - Langmuir-Blodgett monolayer stabilization using supramolecular clips.
AB  - We introduce the concept of stabilization of Langmuir-Blodgett (LB) films using
      dicarboxylate supramolecular clips, as demonstrated by Langmuir isotherms,
      spectroscopic ellipsometry, atomic force microscopy, X-ray photoelectron
      spectroscopy (XPS), and contact angle measurements.

PMID- 23174710
TI  - The value of retrospective patient data in oncology.

PMID- 23174711
TI  - Repression of death consciousness and the psychedelic trip.
AB  - Death is our most repressed consciousness, it inheres our condition as the
      primordial fear. Perhaps it was necessary that this angst be repressed in man or
      he would be hurled against the dark forces of nature. Modern ethos was built on
      this edifice, where the 'denial of death' while 'embracing one's symbolic
      immortality' would be worshipped, so this ideology simply overturned and
      repressed looking into the morass of the inevitable when it finally announced
      itself. Once this slowly pieced its way into all of life, 'death' would soon
      become a terminology in medicine too and assert its position, by giving a push to
      those directly dealing with the dying to shy away from its emotional and
      spiritual affliction. The need to put off death and prolong one's life would
      become ever more urgent. Research using psychedelics on the terminally ill which
      had begun in the 1950s and 1960s would coerce into another realm and alter the
      face of medicine; but the aggression with which it forced itself in the 1960s
      would soon be politically maimed, and what remained would be sporadic outpours
      that trickled its way from European labs and underground boot camps. Now, with
      the curtain rising, the question has etched itself again, about the use of
      psychedelic drugs in medicine, particularly psychedelic psychotherapy with the
      terminally ill. This study is an attempt to philosophically explore death anxiety
      from its existential context and how something that is innate in our condition
      cannot be therapeutically cured. Psychedelic use was immutably linked with
      ancient cultures and only recently has it seen its scientific revival, from which
      a scientific culture grew around psychedelic therapy. How much of what was
      threaded in the ritual and spiritual mores can be extricated and be interpreted
      in our own mechanized language of medicine is the question that nudges many.

PMID- 23174712
TI  - Personalized medicine of esophageal cancer.
AB  - The fatality rate of esophageal carcinomas is high in developing countries,
      making effective treatment desirable. Traditional treatment has now entered into
      the platform, and treatments based on the detection of biomarkers increasingly
      become a trend. This review presents several biomarkers of esophageal cancer,
      including chemotherapy-related biomarkers and targeted drug-related biomarkers,
      and the correlation of these biomarkers with drug response.

PMID- 23174713
TI  - Irradiation-mediated carbon nanotubes' use in cancer therapy.
AB  - Anticancer drugs such as biological therapeutic proteins and peptides are used
      for treatment of a variety of tumors. However, their wider use has been hindered
      by their poor bioavailability and the uncontrollable sites of action in vivo.
      Cancer nano-therapeutics is rapidly progressing, which is being applied for
      solving some limitations of conventional drug delivery systems. To improve the
      bio-distribution of anticancer drugs, carbon nanotubes have been used as one of
      the most effective drug carriers. This review discusses the carbon nanotubes
      mediated methods for the delivery of anticancer drugs, with emphasis on the
      radiation-induced drug-targeted releasing and selective photo-thermal cancer
      therapy.

PMID- 23174714
TI  - Methylenetetrahydrofolate reductase gene polymorphisms (677C > T and 1298A > C)
      in Egyptian patients with non-Hodgkin lymphoma.
AB  - BACKGROUND: Folate metabolism plays an essential role in Deoxyribonucleic acid
      (DNA) synthesis and methylation processes. Deviations in the flux of the folate
      may affect the susceptibility to various cancers including lymphoma. AIM: The aim
      of this study was to investigate the genetic polymorphisms in 5, 10
      methylenetetrahydrofolate reductase (MTHFR 677C/T and 1298A/C) and to evaluate
      its associations with the risk of Non Hodgkin lymphoma. MATERIALS AND METHODS:
      The study included 50 patients with diffuse large B cell lymphoma (DLBCL) as well
      as 50 age matched apparently healthy volunteers (as control). All the subjects
      included in the study were genotyped for the detection of the MTHFR gene
      polymorphisms (677C > T and 1298A > C) by using restriction fragment length
      polymorphism (PCR-RFLP). RESULTS: There were highly statistically significant
      differences between the 2 groups with respect to results of PCR-RFLP for MTHFR
      677C->T polymorphism for CC genotype (P value = 0.001), statistically significant
      differences for CT (P value = 0.048) and TT (P value = 0.038) genotypes; however,
      no statistically significant differences regarding CC/CT or TT/CT alleles (P
      value = 0.052). Also, there were highly statistically significant differences
      between the patient and control groups with regards to the results of MTHFR1298
      A/C polymorphism for the AA, AC genotypes as well as the AA/AC and CC/AC alleles
      (P value < 0.0001), and statistically significant difference regarding CC
      genotype (P value 0.0192). CONCLUSION: In conclusion, this study demonstrated a
      significant association between the MTHFR polymorphisms and the risk of DLBCL.
      Thus the study could support that folate intake together with the genetic basis
      may help in modifying the risk to lymphoma.

PMID- 23174715
TI  - Impact of adjuvant radiation therapy photon energy on quality of life after
      breast conservation therapy: linear accelerator versus the cobalt machine.
AB  - BACKGROUND: Breast conservative therapy (BCT) is a standard treatment option in
      early operable breast cancers (OBC) and a select group of large or locally
      advanced tumors. The present study deals with prospective evaluation of quality
      of life (QOL) score in consecutive patients treated with BCT employing adjuvant
      RT treated with either a cobalt machine or a linear accelerator (LA). MATERIAL
      AND METHODS: Patients of carcinoma breast who underwent BCT were taken into the
      study. Patients with larger breasts (inter-field separation >18-20 cm) were
      treated on LA and those with smaller breasts were treated on cobalt machine. All
      patients received a uniform RT dose (45-50 Gy/25#/5 weeks) to whole breast
      followed by tumor bed boost with suitable energy electrons. Prospective
      evaluation of QOL was done using EORTC QLQ C30 and breast cancer-specific EORTC
      QLQ BR23. QOL evaluation was done at pre-RT, at half completion of RT treatment
      (at 20-23 fractions) and at completion of RT. RESULTS: Pre-RT evaluation GQOL
      scores in patients treated with cobalt and LA were 71.6 and 71.7, respectively (P
      = 0.8). QLQ C30 functional and symptom domain scores were also similar in the
      groups. At RT completion, Global quality of life (GQOL) scores were 67.7 in
      patients treated with cobalt as compared to 77.7 in patients treated with LA (P =
      0.75). Physical function domain scores in cobalt and LA patients were 70.8 and
      80.3, respectively (P = 0.26). Fatigue score was higher in patients treated with
      cobalt (39.1 versus 29.7; P = 0.9). However, there was no difference in other
      functional and symptom domains. There was no significant change in any of the
      EORTC QLQ C30 domains at RT completion as compared to the pre-RT scores.
      CONCLUSION: There is no significant difference in QOL domains between
      appropriately selected patients treated with cobalt and LA. There are no
      significant changes in QOL domain scores at RT conclusion as compared to pre-RT
      baseline in patients treated with cobalt or LA source. A cobalt machine may be
      effectively used to deliver adjuvant RT in appropriately selected BCT patients
      especially in developing countries with limited resources.

PMID- 23174716
TI  - Influence of smoothing algorithms in Monte Carlo dose calculations of cyberknife
      treatment plans: a lung phantom study.
AB  - AIM: The Monte Carlo dose calculation algorithm yields accurate dose
      distributions in heterogeneous media and interfaces. The Monte Carlo calculation
      algorithm provided in the Multiplan Cyberknife treatment planning system
      (Accuray, Sunnyvale, CA, USA) has five different dose-smoothing algorithms in it.
      As the principle of smoothing of these algorithms is different, they can produce
      a disparity in the final dose distribution. The aim of the present study is to
      analyze the influence of these Monte Carlo smoothing algorithms in the final dose
      distribution of cyberknife treatment plans. MATERIALS AND METHODS: An
      anthropomorphic lung phantom with a tumor mimicking ball target was taken for
      this study. The basic optimization was performed with the Ray tracing algorithm.
      The Monte Carlo calculations were introduced with each smoothing algorithm on the
      basic plan and the plans were compared. RESULTS: The Monte Carlo doses were found
      to be lesser than the Ray tracing doses. The dose conformity index was above 4
      for all the smoothing algorithms, while it was only 1.19 for Ray tracing. The
      least coverage of 6.34 was obtained for a weighted average algorithm. The
      deviation between the V100% values of different smoothing algorithms was higher
      than the deviation in V80%. CONCLUSION: The deviations between the smoothing
      algorithms are higher in the high-dose regions, including the prescribing
      isodose, than the low-dose regions of the target, as well as in the organs at
      risk (OAR).

PMID- 23174717
TI  - Epidermal growth factor receptor mutations in female patients with postoperative
      recurrent non-small-cell lung cancer.
AB  - PURPOSE: We did this retrospective study to explore the association between
      epidermal growth factor receptor (EGFR) mutation and clinical features in
      postoperative recurrent female non-small-cell lung cancer (NSCLC). MATERIALS AND
      METHODS: We reviewed clinical data on 86 female patients who had postoperative
      recurrent disease between December 1992 and July 2007. The start of tyrosine
      kinase inhibitor therapy was treated as a censoring event. Corresponding surgical
      specimens of primary tumors were used to test for EGFR mutations. RESULTS: Thirty
      patients presented with local recurrence and distant recurrence was identified in
      56. Thirty-four of the 86 patients (40%) harbored EGFR mutations. Patients with
      distant recurrence were more likely to have EGFR mutations than patients with
      local recurrence (48% versus 23%; P = 0.024). On multivariate analysis, distant
      recurrence was associated with a high frequency of EGFR mutations (OR, 3.3; P =
      0.028). Survival analysis showed poor survival of patients with mutated EGFR (HR,
      2.3; P = 0.017) or with non-adenocarcinoma histology (HR, 3.3; P = 0.001).
      CONCLUSION: The association between recurrence pattern and EGFR mutation status
      was suggested in recurrent female NSCLC patients. In addition, our data indicate
      unfavorable disease process of EGFR mutated tumors. Further studies need to be
      conducted to validate these findings.

PMID- 23174718
TI  - Risk factors for malignancy in patients with solitary thyroid nodules and their
      impact on the management.
AB  - BACKGROUND: Presently it is difficult to differentiate malignancy for thyroid
      nodules by palpation, ultrasonography and fine-needle aspiration cytology (FNAC)
      at the outpatient department, especially for solitary thyroid nodule (STN). So a
      great emphasis should be placed on the STN. AIMS: The objective of this study was
      to investigate the predictive clinicopathological risk factors for malignancy in
      patients with STN and further to provide an appropriate clinical management.
      MATERIALS AND METHODS: The records were reviewed from 265 patients with STN who
      had undergone thyroidectomy in our hospital. All cases were classified as two
      independent groups in terms of the final pathological results to assess the
      independent risk factors using a multinomial logistic regression analysis.
      RESULTS: A multinomial logistic analysis revealed that the male gender,
      microcalcification and cervical lymphadenopathy were independent risk factors
      related to malignancy in patients with STN. The incidence of malignancy in
      patients with 0,1,2,3 risks was 10.71%, 26.6%, 61.43%, and 100%, respectively.
      CONCLUSIONS: Male gender, microcalcification and lymphadenopathy were independent
      risk factors for predicting the malignancy in patients with STN. Patients with
      more than two of those risk factors should be subjected to further examination or
      thyroidectomy. The findings may provide a simple and reasonable management for
      the STN.

PMID- 23174719
TI  - Serum lipid profile in oral cancer and leukoplakia: correlation with tobacco
      abuse and histological grading.
AB  - INTRODUCTION: Role of alterations in serum lipid profile in oral cancer remains
      controversial. The present study aimed to evaluate the implications of altered
      serum lipid profile in patients with oral cancer (OC), oral leukoplakia (OLP),
      and tobacco habits. MATERIALS AND METHODS: Thirty patients with OC, 30 with OLP,
      30 tobacco abusers (TAs), and 30 age and sex matched healthy controls were
      included in the study. Serum lipid profile including total cholesterol (TC), high
      density lipoprotein (HDL), low density lipoprotein (LDL), Very low density
      lipoprotein (VLDL), and triglycerides (Tg) were evaluated using a fully automatic
      Biochemistry analyzer. Difference in lipid profile in various types of TA, that
      is, smokeless tobacco (SLT), smoking tobacco (ST), and a combination (Comb) usage
      of both forms were also analyzed. RESULTS: TC, HDL, and LDL were much lower in
      the OC group compared with control. Although these parameters were low in the OPC
      group compared with controls, the difference was not significant. On histological
      analysis, TC and HDL were found to decrease marginally with loss of tumor
      differentiation in OC. No correlation was found between the mean serum lipid
      profiles and degree of dysplasia in OLP. TC and HDL were significantly lesser in
      all forms of TA when compared with control. CONCLUSIONS: There may be an inverse
      relationship between serum lipid profile and OC. No significant reduction in
      lipid profile was observed in the OLP group. This may indicate that hypolipidemia
      is a late change occurring during carcinogenesis or is an effect rather than the
      cause of cancer.

PMID- 23174720
TI  - Clinicoepidemiological analysis of female breast cancer patients in Kashmir.
AB  - AIM: The aim of this study was to analyze the demographic features, reproductive
      history and stage at disease presentation among the female breast cancer
      patients. DESIGN AND SETTING: The present prospective hospital-based study was
      conducted in Department of Radiation Oncology, University Teaching and Tertiary
      Referral Hospital. MATERIALS AND METHODS: After approval from the Institute's
      ethical committee, 132 female breast cancer patients surgically treated either by
      mastectomy or breast conserving surgery (BCS) and then referred to the department
      of radiation oncology for further management and/or follow-up as per the hospital
      protocol, were enrolled in the study (January 2010 to December 2011) after
      obtaining a written informed consent from the patients. The patients were
      diagnosed by histology [fine needle aspiration cytology (FNAC), true cut or
      excision biopsy], mammography and ultrasonography (USG). The patients were
      analyzed as per the demographic and reproductive history and the stage of disease
      at presentation. The data collected were expressed as percentage (%), mean,
      median and standard deviation (SD). RESULTS: The mean age at presentation was
      46.6 +/- 10.2 years. The majority of patients were from rural areas, married,
      multiparous and post-menopausal. The commonest stage at disease presentation was
      IIb. CONCLUSION: In comparison to the rest of Indian scenario, more awareness
      related to breast cancer among post-menopausal and the rural females is needed.
      The role of peri-menopausal status, which represent 10% (n = 14) patients needs
      to be established in relation to breast cancer.

PMID- 23174721
TI  - The effect of rib and lung heterogeneities on the computed dose to lung in Ir-192
      high-dose-rate breast brachytherapy: Monte Carlo versus a treatment planning
      system.
AB  - AIMS: This study investigates to what extent the dose received by lungs from a
      commercially available treatment planning system, Ir-192 high-dose-rate (HDR), in
      breast brachytherapy, is accurate, with the emphasis on tissue heterogeneities,
      and taking into account the presence of ribs, in dose delivery to the lung.
      MATERIALS AND METHODS: A computed tomography (CT) scan of a breast was acquired
      and transferred to the 3-D treatment planning system and was also used to
      construct a patient-equivalent phantom. An implant involving 13 plastic catheters
      and 383 programmed source dwell positions were simulated, using the Monte Carlo N
      Particle eXtended (MCNPX) code. The Monte Carlo calculations were compared with
      the corresponding commercial treatment planning system (TPS) in the form of
      percentage isodose and cumulative dose-volume histogram (DVH) in the breast,
      lungs, and ribs. RESULTS: The comparison of the Monte Carlo results and the TPS
      calculations showed that a percentage of isodose greater than 75% in the breast,
      which was located rather close to the implant or away from the breast curvature
      surface and lung boundary, were in good agreement. TPS calculations overestimated
      the dose to the lung for lower isodose contours that were lying near the breast
      surface and the boundary of breast and lung and were relatively away from the
      implant. CONCLUSIONS: Taking into account the ribs and entering the actual data
      for breasts, ribs, and lungs, revealed an average overestimation of the dose by a
      factor of 8% in the lung for TPS calculations. Therefore, the accuracy of the TPS
      results may be limited to regions near the implants where the treatment is
      planned, and is a more conservative approach for regions at boundaries with
      curvatures or tissues with a different material than that in the breast.

PMID- 23174722
TI  - Cell cycle analysis of the CD133(+) and CD133(-) cells isolated from human
      colorectal cancer.
AB  - AIM: The CD133 antigen has been identified as a putative stem cell marker in
      colorectal cancer tissues. The aim of this study was to investigate the cell
      cycle state of CD133(+) and CD133(-) cells, isolated from primary human
      colorectal tumors. MATERIALS AND METHODS: After mechanical and enzymatic
      dissociation of the tumor samples, CD133(+) and CD133(-) subsets were identified
      and separated by magnetic cell sorting. Flow cytometric analysis was performed to
      compare the cell cycle of both CD133(+) and CD133(-) cells isolated from primary
      and liver metastatic cancer cells. RESULTS: The results indicated that CD133(+)
      cells isolated from both primary and liver metastatic colorectal cancers were
      found in higher percentage in the G0/G1 phases. However, the CD133(-) cells
      isolated from primary colorectal cancers were predominantly found in the S and
      G2/M phases. Surprisingly, the CD133(-) cells isolated from liver metastatic
      colorectal cancers were mostly found in the G0/G1 phase. CONCLUSION: The present
      study provides evidence that CD133(+) cells are in a quiescent state in
      colorectal cancer, representing a mechanism that would at least partially explain
      chemotherapy resistance and tumor recurrence in post-therapy patients.

PMID- 23174723
TI  - Anti-tumor effect of Ardisia crispa hexane fraction on 7, 12
      dimethylbenz[alpha]anthracene-induced mouse skin papillomagenesis.
AB  - CONTEXT: Ardisia crispa Thunb. A. DC (Myrsinaceae) or locally known as hen's eyes
      has been used in local folk medicine as a remedy in various illnesses.
      Previously, it has been reported to inhibit various inflammatory diseases.
      However, research done on this plant is still limited. AIMS: In the present
      study, the hexane fraction of the A. crispa root (ACRH) was evaluated on the peri
      initiation and promotion phases of skin carcinogenesis. MATERIALS AND METHODS:
      This two-stage skin carcinogenesis was induced by a single topical application of
      7,12-dimethylbenz(alpha)anthracene (DMBA) and promoted by repeated treatment with
      croton oil for 10 weeks in Imprinting Control Region (ICR) mice. Morphological
      observation would be conducted to measure tumor incidence, tumor burden, and
      tumor volume. Histological evaluation on the skin tissue would also be done.
      RESULTS: The carcinogen control group exhibited 66.67% of tumor incidence.
      Although, in the ACRH-treated groups, at 30 mg/kg, the mice showed only 10% of
      tumor incidence with a significant reduction (P < 0.05) in the values of tumor
      burden and tumor volume of 2.00 and 0.52 mm(3), respectively. Furthermore, the
      result was significantly lower than that of the carcinogen and curcumin control.
      At 100 mg/kg, ACRH showed a comparable result to carcinogen control. On the
      contrary, at 300 mg/kg, ACRH exhibited 100% tumor incidence and showed a
      significant elevated (P < 0.05) value of tumor burden (3.80) and tumor volume
      (14.67 +/- 2.48 mm(3)). CONCLUSIONS: The present study thus demonstrates that the
      anti-tumor effect of the chemopreventive potential of ACRH is at a lower dosage
      (30 mg/kg bwt) in both the initiating and promotion period, yet it exhibits a
      promoting effect at a higher dosage (300 mg/kg bwt).

PMID- 23174724
TI  - Clinical outcomes of reirradiation of brain metastases from small cell lung
      cancer with Cyberknife stereotactic radiosurgery.
AB  - PURPOSE: To analyze outcomes of reirradiation with stereotactic radiosurgery
      (SRS) for patients with brain metastases from small cell lung cancer (SCLC).
      MATERIALS AND METHODS: We reviewed the clinical outcomes of 27 patients with
      brain metastases from SCLC treated with CyberKnife(r) robotic radiosurgery
      (Accuray Inc., Sunnyvale, CA). Kaplan-Meier analyses were used to estimate local
      control (LC), intracranial control (IC), and overall survival (OS). The Graded
      Prognostic Assessment (GPA) prognostic index was determined with a Cox Regression
      analysis to model predictors of outcome. RESULTS: The median follow-up from SRS
      was 12 months (2-24 months). Nine patients (32.1%) had Graded Prognostic
      Assessment (GPA) scores 0-1 and 19 patients (67.9%) had GPA scores 1.5-2.5. 19
      patients (70%) received whole brain radiation therapy (WBRT) and 8 patients (30%)
      received prophylactic cranial irradiation (PCI). The median SRS dose was 20.5 Gy
      (15-24 Gy) in 1 fraction. Actuarial LC at 6 months and 12 months was 76.5% and
      76.5%, respectively. New metastases outside the treated area developed in 60% of
      assessable patients at a median 3.5 months; 78% received previous WBRT. The
      median OS was 3 months from SRS with actuarial 6-month and 12-month rates of 25%
      and 3.6%, respectively. On multivariate analysis no factors were associated with
      LC, IC, or OS. CONCLUSIONS: SRS for reirradiation of brain metastases from SCLC
      is safe and achieves local tumor control in the majority of patients. Despite
      SRS, these patients are at high risk of distant brain failure.

PMID- 23174725
TI  - Combination of Ononis hirta and Bifidobacterium longum decreases syngeneic mouse
      mammary tumor burden and enhances immune response.
AB  - BACKGROUND: The resistance of solid tumors to conventional therapies has prompted
      the need for alternative therapies. AIM: To evaluate in vitro and in vivo effect
      of extracts from Ononis hirta against resistant mouse mammary gland cell line (66
      cl-4-GFP) and to use a combination of Ononis hirta extract with Bifidobacterium
      longum to target resistant solid tumors in mice. MATERIALS AND METHODS: Different
      solvent extracts of Ononis hirta were prepared and their in vitro
      antiproliferative activity was tested against 66 cl-4-GFP cell line using 3-(4, 5
      dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay. Thin layer
      chromatography (TLC) and high-performance liquid chromatography (HPLC) were used
      to identify the active extracts. Balb/C mice were transplanted with 66 cl-4-GFP
      cell line and in vivo antitumor activity was assessed for the plant extract,
      Bifidobacterium longum, and a combination of plant extract and Bifidobacterium
      longum. Histological examination of tumors was performed using standard
      hematoxylin/eosin staining protocol while gram stain was used to detect the
      presence of anaerobic bacteria in these sections. RESULTS: A combination of
      Ononis hirta methanol extract and Bifidobacterium longum showed high ability in
      targeting solid mammary gland tumors in mice. It also induced extensive necrosis
      in these tumors. Thirty percent of mice treated with such combination were cured
      of their cancers. The mechanism underlying this anticancer activity involves
      immune system activation exemplified by the observed rejection of reinoculated
      tumors by cured mice. Chemical TLC analysis of the active methanol extract showed
      the presence of flavonoids, terpenoids, and alkaloids. HPLC analysis confirmed
      the presence of flavonoids and alkaloids in Ononis hirta methanol extract.
      CONCLUSION: The complete regression of the tumor is encouraging and shows that
      plant extracts in combination with Bifidobacterium longum is an inviting option
      to treat solid tumors.

PMID- 23174726
TI  - Extra osseous osteosarcoma of the retroperitoneum: an unusual entity.
AB  - Extra-osseous osteosarcomas constitute about 1-1.2% of all osteosarcomas. The
      most common sites are the extremities, thorax, and the abdomen. Retroperitoneal
      osteosarcomas are rare and very few cases have been reported. They are similar in
      their biology to high grade soft tissue sarcomas. R0 resection appears to be the
      best possible treatment for these tumors. All three variants of conventional
      osteosarcoma--osteoblastic, chondroblastic, and fibroblastic have been described
      in these tumors. Chemotherapy has been attempted with adriamycin-based regimens
      with poor results. Unlike extremity osteosarcomas, these tumors have been found
      to be chemoresistant. The 5 year survival has ranged from a dismal 12% to about
      25%. We report a 46-year-old male who presented with a kidney tumor infiltrating
      the descending colon, but turned out to be an extra osseous osteosarcoma. An R0
      resection was done and adjuvant chemotherapy given.

PMID- 23174727
TI  - Adjuvant pelvic irradiation for cervical cancer in the setting of a transplanted
      pelvic kidney.
AB  - Postoperative radiation therapy is often needed following resection for
      gynecological cancers. A pelvic kidney, whether ectopic or transplanted, is
      considered an absolute contraindication for radiation if the organ is left in
      place. A 45-year-old, immunosuppressed patient with FIGO IB1 cervical
      adenocarcinoma was treated with intensity-modulated radiation therapy (IMRT) to
      45 Gy to the modified whole pelvis with a boost to 59.4 Gy to high-risk areas
      despite having a transplanted kidney in the right iliac fossa. The irradiation
      prevented further local failure in the pelvis at 36-month follow-up with no
      decrement in renal function. Radiation to the modified pelvis using IMRT while
      avoiding the renal allograft is technically feasible and should be offered to
      more high-risk patients.

PMID- 23174728
TI  - Acrometastasis to hand in vaginal carcinoma: a rare entity.
AB  - Although metastases to bones from solid tumors are very common, involvement of
      small bones of the hands is extremely rare. We report the first case of
      acrometastasis in vaginal carcinoma. We present a 65-year-old multiparous woman
      with FIGO Stage II vaginal carcinoma. The patient received treatment with
      external beam radiotherapy followed by brachytherapy. She had complete response
      to above treatment. Eleven months later, she presented with swelling on dorsum of
      hand. Investigations revealed metastasis to 4th metacarpal bone with lung
      metastasis. Hence, we present a patient with metastasis of carcinoma vagina to
      the 4 th metacarpal to draw the attention for the potential of such lesions to be
      developed in this region. It should be remembered that bone metastasis at unusual
      sites might be seen in vaginal carcinoma. We present this case because of its
      rarity and for documentation and discussion.

PMID- 23174729
TI  - Primary extra-gastrointestinal stromal tumor of the omentum.
AB  - Gastrointestinal stromal tumors (GISTs) are mesenchymal tumors originating from
      interstitial cells of Cajal or related stem cell-like precursors present in the
      wall of the gastrointestinal tract. However, identical tumors originating from
      areas other than the gastrointestinal tract have been reported which are
      histologically identical to the usual GISTs. We are reporting a case of primary
      omental GIST in a 57-year-old female.

PMID- 23174730
TI  - Metachronous solitary metastasis of papillary thyroid cancer in the cavernous
      sinus: case report and review of literature.
AB  - Papillary carcinoma is a well-differentiated type of thyroid carcinoma with very
      good overall prognosis. The commonest site of metastases is the lymph node,
      distant metastases being rare. We present a case of a 52-year-old male who
      presented with a solitary metastasis in the left para-sellar region and cavernous
      sinus more than three years after treatment of primary. Given the atypical
      radiological features and longstanding symptoms, a surgical excision was
      performed and focal radiotherapy was given after confirmation of the diagnosis.
      We discuss this case and review the relevant literature.

PMID- 23174731
TI  - Gemcitabine-induced radiation recall phenomenon in a post-operative and post
      radiotherapy case of peri-ampullary carcinoma during adjuvant chemotherapy.
AB  - Radiation recall phenomenon is an inflammatory process occurring at sites of
      previous radiation subsequent to administration of pharmacologic agents. The most
      common chemotherapeutic agents implicated with radiation recall phenomenon are
      anthracyclines and taxanes. Skin is the most common site for radiation recall.
      About 63% of the radiation recall events are reported to manifest as dermatitis.
      This finding differs from radiation recall due to Gemcitabine, in which
      approximately 70% cases manifested as inflammation of internal organs or tissues
      and 30% manifested as dermatitis. Here, we report a case of post-operative peri
      ampullary carcinoma who developed radiation recall dermatitis during adjuvant
      chemotherapy with inj. Gemcitabine and inj. Carboplatin after concurrent
      chemoradiation with capecitabine.

PMID- 23174732
TI  - Acute non-ST elevation myocardial infarction following paclitaxel administration
      for ovarian carcinoma: a case report and review of literature.
AB  - We report a case of an acute non-ST elevation myocardial infarction (AMI) induced
      by paclitaxel in a patient with ovarian cancer. A 45-year-old premenopausal lady
      without any co-morbidity was started on the first cycle of neoadjuvant
      chemotherapy with paclitaxel-based regimen for advanced stage ovarian cancer. The
      patient developed chest pain 3 h after paclitaxel infusion with characteristic
      electrocardiographic changes of antero-apical myocardial infarction. The patient
      recovered on conservative medical management with reversion of electrocardiogram
      (ECG) changes. Cardiac ischemia and myocardial infarction, possibly due to
      coronary vasospasm, are rare adverse effects of paclitaxel with reported
      incidence of 0.26%. We have reported a case of paclitaxel-induced myocardial
      infarction with reversible cardiac dysfunction. The possibility of myocardial
      infarction should be considered in patients who develop chest pain or other
      symptoms after paclitaxel infusion.

PMID- 23174733
TI  - Mixed squamous and large-cell carcinoma of the lung: a case study and literature
      review.
AB  - Lung tumors with combined histological pattern are seldom seen exhibiting a more
      aggressive clinicopathological picture than tumors with a single histology.
      Herein, we present a 58-year-old male with mixed squamous and large-cell lung
      carcinoma. The patient was initially diagnosed through fluoroscopy-guided
      transbronchial lung biopsy with large-cell lung carcinoma of the left upper lobe.
      He received neo-adjuvant chemotherapy and then underwent left upper lobectomy.
      Postoperative pathological diagnosis was combined squamous and large-cell
      neuroendocrine carcinoma. Two months after surgery, restaging revealed brain
      metastatic deposits. Local radiotherapy was promptly applied with relatively good
      response and the patient is under observation eight months after diagnosis. A
      brief review of the current literature is also included with special emphasis on
      the clinicopathologic aspects and prognosis of lung tumors with mixed histology.

PMID- 23174734
TI  - Adult primary pleomorphic leiomyosarcoma of forearm with axillary lymph node
      metastasis: a case report and literature review.
AB  - A rare case of advanced pleomorphic leiomyosarcoma of forearm with axillary lymph
      node metastasis in a young adult, diagnosed with the aid of immunohistochemistry
      and electron microscopic examinations together with a review of the literature
      are reported. The primary tumor involved the extensor and flexor aspect of
      forearm without bone involvement and metastasized to the axillary lymph nodes.
      Patient showed poor treatment outcome with adjuvant chemoradiotherapy following
      incomplete surgery.

PMID- 23174735
TI  - Malignant amelanotic melanoma--a diagnostic surprise: Flurodeoxyglocose Positron
      Emission Tomography-Computed Tomography and immunohistochemistry clinch the
      'final diagnosis'.
AB  - Amelanotic melanoma is a rare malignancy and the prognosis is usually poorer than
      that of pigmented melanomas, because of delay in establishing the correct
      diagnosis, and in treatment initiation. In our case report, we present a the
      Flurodeoxyglocose Positron Emission Tomography-Computed Tomography (FDG PET/CT)
      findings of a patient suffering from malignant amelanotic melanoma and its
      histopathological confirmation and immunohistochemistry (IHC) correlation In the
      described case, amelanotic melanoma masqueraded as adenocarcinoma of the rectum
      in the pathology as well the clinical course. Our case highlights the importance
      of obtaining a tissue diagnosis and IHC confirmation whenever unusual PET/CT
      findings are encountered.

PMID- 23174736
TI  - Pitfalls in diagnosing specific subtypes of carcinoma breast on fine needle
      aspiration cytology: a report of two cases with review of literature.
AB  - Fine needle aspiration cytology (FNAC) is a useful procedure that can be
      conveniently performed in the outpatient department (OPD) and can be used in the
      subtyping of breast carcinomas. However, some specific subtypes can cause a
      hindrance to that. We present two such cases, one of tubulolobular carcinoma
      breast and the other of squamous cell carcinoma breast that were missed on FNAC,
      and subsequently diagnosed on histopathology and by immunohistochemistry. A
      thorough knowledge of the cytological features of the subtypes and the use of
      immunocytochemistry can appropriately make FNAC a standard, accurate, and simple
      OPD procedure, thus helping us in arriving at specific diagnosis.

PMID- 23174737
TI  - Value of bone marrow examination in Hodgkin lymphoma: report of three cases with
      review of literature.
AB  - Bone marrow involvement by Hodgkin lymphoma is rare with an average incidence of
      10%. However, the incidence of bone marrow involvement has been shown to be less
      than 1% in patients with clinical stage IA or IIA disease. The involvement of the
      marrow in a patient with Hodgkin lymphoma represents stage IV disease. We report
      our experience wherein three cases of marrow involvement were picked up on bone
      marrow aspirates/ -imprints and confirmed on trephine biopsy. In this paper we
      wish to highlight the significance of bone marrow examination in the initial
      diagnosis and staging of even clinically early stage Hodgkin lymphoma. Staging
      investigations performed at the time of diagnosis for patients with Hodgkin
      lymphoma are vital for determining the appropriate treatment and prognosis.

PMID- 23174738
TI  - Somatostatin analog and mTOR inhibitor treatment of Merkel cell tumor.

PMID- 23174739
TI  - Merkel cell carcinoma of the auricle: a treacherous skin tumor.

PMID- 23174740
TI  - Pericardial effusion and the unsuspected culprit.

PMID- 23174741
TI  - A vanishing act: the incredible erlotinib.

PMID- 23174742
TI  - Three concerns with regards to the utilization of COX-2 inhibitor (celecoxib) in
      combination with standard chemoradiotherapy for nasopharyngeal carcinoma.

PMID- 23174743
TI  - Malignant ectomesenchymoma of paranasal sinuses with proptosis and nodal
      involvement.

PMID- 23174744
TI  - RNA-templated molecule release induced protein expression in bacterial cells.
AB  - We have developed a system to release a biologically active molecule in response
      to the sequence of a target gene. The releasing system, which was triggered by
      the reduction of an azidomethyl group, was successfully applied to protein
      expression induced by the release of IPTG triggered by endogenous RNA in
      bacterial cells.

PMID- 23174745
TI  - Diabetic cardiomyopathy: pathophysiological mechanisms and cardiac dysfuntion.
AB  - Several experimental, pathological, epidemiological, and clinical studies have
      clearly depicted that diabetes mellitus results in cardiac functional and
      structural changes. Diabetic cardiomyopathy results in both structural and
      functional alterations in the myocardium. Several mechanisms have been implicated
      in the pathophysiology of diabetic cardiomyopathy. Of these, metabolic
      disturbances, myocardial fibrosis, small vessel disease, and cardiac autonomic
      neuropathy are the major players in the pathophysiology of diabetic
      cardiomyopathy. This review is intended to discuss various such
      pathophysiological mechanisms of diabetic cardiomyopathy. We have also described
      the systolic and diastolic dysfunctioning and its corelation to structural
      changes in diabetes.

PMID- 23174746
TI  - Orofacial dyskinesia induced by nasal Ritalin(R) (methylphenidate) sniffing: a
      rare case report from Switzerland.
AB  - Ritalin(r) (methylphenidate) is an amphetamine-like prescription stimulant
      commonly used in the treatment of attention deficit hyperactivity disorder in
      children and adults. Recently, the recreational use of Ritalin has increased,
      particularly among young adults. Well-known symptoms of intoxication include
      signs of sympathetic nervous stimulation, such as agitation, anxiety,
      tachycardia, hypertension, headache, tremor, and dizziness. This case report
      describes oral dyskinesia as a rare presentation of Ritalin intoxication, with
      the review of pathophysiology and some epidemiological data.

PMID- 23174747
TI  - Combination of flotation and flame atomic absorption spectrometry for
      determination, preconcentration and separation of trace amounts of metal ions in
      biological samples.
AB  - An efficient enrichment procedure based on the combination of flame atomic
      absorption spectrometry (FAAS) and flotation for determination of Cd(2+), Ag(+)
      and Zn(2+) ions in various biological samples using new collector is studied. The
      influence of pH, amount of 2-(((1H-benzo[d]imidazol-2-yl)methoxy)methyl)-1H
      benzo[d]imidazole (HBIMMHBI) as collector, sample matrix, type and amount of
      eluting agent, type and amount of surfactant as floating agent, ionic strength
      and air flow rates on the extraction efficiency were evaluated and optimized. It
      is ascertained that under study metal ions is preconcentrated simultaneously from
      matrix in the presence of 0.005 M HBIMMHBI, 0.085% (w/v) of SDS form 750 mL at pH
      6.5. The floated complexes metal ions eluted quantitatively with 6 mL of 1.0 M
      HNO3 in methanol lead to achieve preconcentration factor of 125. The detection
      limits for analyte ions were in the range of 1.3-2.4 ng mL(-1), with recoveries
      more than 95% and relative SD lower than 4%.

PMID- 23174748
TI  - Anti-inflammatory properties of anthraquinones and their relationship with the
      regulation of P-glycoprotein function and expression.
AB  - There is a growing interest in natural products that potentially have anti
      inflammatory properties and inhibit P-glycoprotein (P-gp) function. In this
      report, we assessed the effects of anthraquinone derivatives from rhubarb on LPS
      induced RAW 264.7 macrophages to determine their anti-inflammatory potential. The
      derivatives were also tested in Caco-2 cell lines to evaluate the inhibition of
      the drug efflux function of P-gp. The transport abilities were examined and the
      cellular accumulation of rhodamine-123 (R-123) was also measured. Electorphoretic
      mobility shift assay (EMSA) was performed to check the activator protein-1 (AP-1)
      DNA binding affinity. Five anthraquinones were tested to determine their
      inhibitory activities on NO production and the protein and mRNA expression of
      inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). Furthermore,
      the level of prostaglandin E(2) (PGE(2)) was determined in LPS-induced RAW264.7
      macrophages. Emodin was found to be the most potent inhibitor, and it also
      reduced paw swelling in the mouse model of carrageenan-induced paw edema. In Caco
      2 cells, emodin elevated the accumulation of R-123 and decreased the efflux ratio
      of R-123, which indicates the inhibition of P-gp function. The inhibition of COX
      2 protein by emodin paralleled the decrease in P-gp expression. In addition,
      mitogen-activated protein kinase (MAPK) expression was decreased through the
      prevention of AP-1 DNA binding, which leads to downregulation in the expression
      of P-gp. Our data indicate that the decrease of P-gp expression is caused by the
      decreased expression of COX-2 through the MAPK/AP-1 pathway. Based on our
      results, we suggest that anti-inflammatory drugs with COX-2 inhibitory activity
      might be used to modulate P-gp function and expression.

PMID- 23174749
TI  - Systematic review of Purtscher's and Purtscher-like retinopathies.
AB  - PURPOSE: (1) To describe the clinical characteristics of Purtscher and Purtscher
      like retinopathies, including etiologies, fundoscopic signs, results of
      complementary investigation, treatments, and outcomes. (2) To compare visual
      acuity (VA) of patients receiving corticosteroids for PuR compared with
      observation. METHODS: Systematic review of several databases (1980-2010):
      Medline, EMBASE, ISI, EBSCO, Science Direct and Google Scholar. Study selection
      criteria included: (A) Studies of PuR with ophthalmology assessments; (B) >=3 of
      5 diagnostic criteria of PuR; (C) Quantified VA at presentation. For quantitative
      assessment (purpose 2), we selected only studies that reported whether
      corticosteroids were administered, and with vision assessments after at least 1
      month. RESULTS: (1) From 670 studies initially found, 40 were included (68 cases,
      110 eyes): 1 prospective, 5 case series, and 34 case reports. Mean VA at
      presentation was 1.3 logMAR (logarithm of the minimum angle of resolution)
      (<20/200; range: 20/20-light perception). Purtscher flecken were underreported.
      Trauma and acute pancreatitis were the most frequent etiologies. There were six
      deaths, all with systemic associations. (2) There was no statistically
      significant difference between VA improvement for patients treated with
      corticosteroids compared with observation. Visual prognostic factors identified
      included etiology (pancreatitis and trauma were associated with higher
      probability of visual improvement) and male gender. CONCLUSION: Due to
      limitations of case reports and series, the presented data are only useful as
      broad characterizations of the clinical course of PuR. Further studies, possibly
      including trials to assess the effectiveness of corticosteroids use, and larger
      prospective cohort studies, are necessary, but may not be feasible to conduct.

PMID- 23174750
TI  - Radiotherapy for ocular tumours.
AB  - Ocular tumours present a therapeutic challenge because of the sensitive tissues
      involved and the necessity to destroy the tumour while minimising visual loss.
      Radiotherapy (RT) is one of several modalites used apart from surgery, laser,
      cryotherapy, and chemotherapy. Both external beam RT (EBRT) and brachytherapy are
      used. Tumours of the bulbar conjunctiva, squamous carcinoma and malignant
      melanoma, can be treated with a radioactive plaque: strontium-90, ruthenium-106
      (Ru-106), or iodine-125 (I-125), after excision. If the tumour involves the
      fornix or tarsal conjunctiva, proton therapy can treat the conjunctiva and spare
      most of the eye. Alternatively, an I-125 interstitial implant can be used with
      shielding of the cornea and lens. Conjunctival mucosal-associated lymphoid tissue
      lymphoma can be treated with an anterior electron field with lens shielding and
      25-30 Gray (Gy) in 2 Gy fractions. Discrete retinoblastoma (RB), too large for
      cryotherapy or thermolaser, or recurrent after these modalities, can be treated
      with plaque therapy, I-125, or Ru-106. For large RB, multiple tumours, or
      vitreous seeds the whole eye can be treated with an I-125 applicator, sparing the
      bony orbit, or with EBRT, under anaesthetic, using X-rays or proton therapy with
      vacuum contact lenses to fix the eyes in the required position. Post-enucleated
      orbits at risk for recurrent RB can be treated with an I-125 implant with
      shielding to reduce the dose to the bony orbit. Uveal malignant melanomas can be
      treated with plaque or proton therapy with excellent local control. Preservation
      of vision will depend on the initial size and location of the tumour.

PMID- 23174751
TI  - Personalized treatment of uveal melanoma.
AB  - Personalized treatment of uveal melanoma involves the tailoring of all aspects of
      care to the condition, needs, wishes, and fears of the patient, taking account of
      the individual's circumstances. When selecting between radiotherapy, surgical
      resection, and phototherapy, or when deciding how best to combine these different
      therapeutic modalities, it is necessary to understand the patients utilities,
      with respect to tumour control, visual conservation, and preservation of the eye,
      so as to prioritize outcomes accordingly. For example, such considerations would
      influence the width of the safety margins when administering radiotherapy,
      according to whether the patient considers it more important to conserve vision
      or to guarantee tumour control. With 'suspicious naevi', the choice between
      observation, immediate treatment, and biopsy is complicated by the lack of
      adequate survival data on which to base rational decisions, making it necessary
      for both patient and doctor to accept uncertainty. Personalized care should
      involve close relatives, as appropriate. It must also adapt to changes in the
      patient's needs over time. Such personalized care demands the ability to respond
      to such needs and the sensitivity to identify these requirements in the first
      place. Personalized treatment enhances not only the patient's satisfaction but
      also the 'job satisfaction' of all members of the multidisciplinary team,
      improving quality of care.

PMID- 23174752
TI  - Which visual acuity measurements define high-quality care for patients with
      neovascular age-related macular degeneration treated with ranibizumab?
AB  - PURPOSE: The purpose of this study is to define which visual acuity (VA)
      measurements are the best indicators of high-quality care for patients receiving
      intravitreal ranibizumab for neovascular age-related macular degeneration (nAMD).
      METHODS: Analysis of prospectively collected data recorded within an electronic
      medical record system on treatment-naive, first-eligible eyes with nAMD, treated
      with ranibizumab using an as-needed treatment regimen with a minimum follow-up of
      1 year. Data collection included the following: age, gender, laterality, type of
      nAMD, VA, central 1 mm OCT retinal thickness, number of intravitreal injections,
      and number of follow-up assessments. RESULTS: Data were available on the first
      treated eye from 406 patients with at least 1 year follow-up; of these, 198 had
      data at 2 years. The mean baseline VA of 54.4 Early Treatment Diabetic
      Retinopathy Study letters improved to 58.5 letters at 12 months and to 56.8
      letters at 24 months. The mean VA changes from baseline to 1 year were +6.5,
      +7.5, +1.7, and -1.5 letters, respectively, for baseline VA categories of 23-35,
      36-55, 56-70, and >70 letters. Change in mean VA from the end of the loading
      phase to year 1 ranged from -2.9 to +1.4 letters for the different baseline VA
      categories. The mean number of injections were similar across baseline VA
      categories ranging from 5.7 to 6.0 injections in year 1 and from 3.3 to 3.8 in
      year 2. CONCLUSIONS: This large, real-world series demonstrates that mean change
      in VA is largely a function of selection criteria and baseline VA. The quality of
      a service is therefore better judged by actual VA outcomes and maintenance of
      vision after the loading phase.

PMID- 23174753
TI  - Oncocytic adenocarcinoma of the lacrimal gland: an unusual presentation.

PMID- 23174754
TI  - Deficits in male sexual behavior in adulthood after social instability stress in
      adolescence in rats.
AB  - There is increasing evidence that exposure to stressors in adolescence has long
      lasting effects on emotional and cognitive behavior, but little is known as to
      whether reproductive functions are affected. We investigated appetitive and
      consummatory aspects of sexual behavior in male rats that were exposed to chronic
      social instability stress (SS, n=24) for 16 days in mid-adolescence compared to
      control rats (CTL, n=24). Over five sexual behavior test sessions with a
      receptive female, SS rats made fewer ejaculations (p=0.02) and had longer
      latencies to ejaculation (p=0.03). When only data from rats that ejaculated in
      the fifth session were analyzed, SS rats (n=18) had reduced copulatory efficiency
      (more mounts and intromissions before ejaculation) compared to CTL rats (n=19)
      (p=0.004), and CTL rats were twice as likely as SS rats to make more than one
      ejaculation in the fifth session (p=0.05). Further, more CTL (14/24) than SS
      (5/25) rats ejaculated in four or more sessions (p=0.05). SS rats had lower
      plasma testosterone concentrations than CTL rats (p=0.05), but did not differ in
      androgen receptor, estrogen receptor alpha, or Fos immunoreactive cell counts in
      the medial preoptic area. The groups did not differ in a partner preference test
      administered between the fourth and fifth sexual behavior session. The results
      suggest that developmental history contributes to individual differences in
      reproductive behavior, and that stress exposures in adolescence may be a factor
      in sexual sluggishness.

PMID- 23174756
TI  - Fluorescent labeling and tracking of nanoclay.
AB  - We report a methodology developed to detect and track stable fluorescent-labeled
      nanoclay, in polymer-clay nanocomposite films, and in a contact solvent after
      migration testing. Fluorescein-5-maleimide (fluorescein) or tetramethylrhodamine
      5-maleimide (rhodamine) was covalently bonded to organically modified
      montmorillonite (o-MMT). Fluorescein- and rhodamine-labeled nanoclay showed good
      thermal stability up to 220  degrees C and the rhodamine-labeled nanoclay
      remained stable at 250  degrees C. Confocal laser scanning microscopy was used to
      confirm the tagging and to detect the fluorescent-labeled nanoclays in various
      systems.

PMID- 23174757
TI  - Interaction between TGF-beta and ACE2-Ang-(1-7)-Mas pathway in high glucose
      cultured NRK-52E cells.
AB  - Transforming growth factor-beta (TGF-beta) is pivotal in diabetic nephropathy
      (DN). Angiotensin converting enzyme-2 (ACE2) converts angiotensin II (Ang II) to
      angiotensin 1-7 (Ang-(1-7)), which binds to Mas. Proximal tubular ACE2 is
      decreased in DN. ACE2 deficiency exacerbates whereas ACE2 overexpression
      attenuates DN. Thus, we investigated the mechanism of high glucose-decreased ACE2
      in terms of the interaction between TGF-beta and ACE2-Ang-(1-7)-Mas in NRK-52E
      cells. We found that high glucose increased TGF-beta1. SB431542 attenuated high
      glucose-inhibited ACE2 and Mas and Ang-(1-7) conversion from Ang II while
      attenuating high glucose-induced fibronectin. TGF-beta1 also decreased ACE2 and
      Mas and Ang-(1-7) conversion from Ang II. A779 attenuated Ang-(1-7)-decreased TGF
      beta1 and Ang-(1-7)-activated JAK2-STAT3. Moreover, A779, LY294002 and AG490
      attenuated Ang-(1-7)-inhibited TGF-beta1. The combination of Ang-(1-7) and Mas
      attenuated TGF-beta1 (but not high glucose)-induced fibronectin. Thus, high
      glucose decreases ACE2 via TGF-betaR in NRK-52E cells. Additionally, there is a
      negative feedback function between TGF-beta and ACE2, and the combined inhibition
      of TGF-beta and activation of the ACE2-Ang-(1-7)-Mas may be useful for treating
      diabetic renal fibrosis.

PMID- 23174758
TI  - Angiotensin AT2 receptor activates the cyclic-AMP signaling pathway in eel.
AB  - A unique angiotensin type 2 receptor (AT2) that induces a cAMP signaling pathway
      was cloned and characterized for the first time in fish, Anguilla japonica.
      Phylogeny and synteny results showed that the AT2s among fishes and tetrapods
      share the same origin despite a sub-cluster formation among eel, salmon, and
      zebrafish. The eel AT2 was expressed abundantly in the spleen and localized at
      straight arterioles and ellipsoid regions prior to the sinusoid, suggesting a
      role in the regulation of microcirculation and/or immune response. Various
      angiotensin (Ang) peptides, including Ang II, Ang III, and Ang IV, were detected
      in the spleen by a radioimmunoassay coupled with HPLC separation, and these
      endogenous peptides stimulated a cAMP signaling, which has no crosstalk with cGMP
      pathway. The common and contrasting features of AT2 between fishes and mammals
      imply some ancestral characters of AT2, which are important information for
      receptor binding and evolutionary studies.

PMID- 23174755
TI  - NRF2 and p53: Januses in cancer?
AB  - The transcription factor nuclear factor (erythroid-derived 2)-like 2, also known
      as NFE2L2 or NRF2, is a master regulator of the anti-oxidative stress response
      and positively controls the expression of a battery of anti-oxidative stress
      response proteins and enzymes implicated in detoxification and glutathione
      generation. Although its detoxifying activity is important in cancer prevention,
      it has recently been shown that cancer cells also exploit its protective
      functions to thrive and resist chemotherapy. NRF2 was also shown to the pentose
      phosphate pathway and glutaminolysis, which promotes purine synthesis for
      supporting rapid proliferation and glutathione for providing anti-oxidative
      stress protection. Evidence obtained from cancer patients and cell lines suggest
      that NRF2 is highly active in a variety of human cancers and is associated with
      aggressiveness. p53 is a tumor suppressor that also promotes an anti-oxidative
      stress metabolic program and glutaminolysis. Here we will discuss the
      similarities between NRF2 and p53 and review evidence that p53 might be exploited
      by cancer cells to gain protection against oxidative stress, as is the case for
      NRF2. We discuss findings of co-regulation between these transcription factors
      and propose possible therapeutic strategies that can be used for treatment of
      cancers that harbor WT p53 and express high levels of NRF2.

PMID- 23174759
TI  - Microwave-assisted synthesis and up-down conversion luminescent properties of
      multicolor hydrophilic LaF3:Ln3+ nanocrystals.
AB  - Monodisperse water-soluble LaF(3):Ln(3+) nanocrystals (NCs) have been
      successfully fabricated via a fast, facile and environmentally-friendly microwave
      assisted modified polyol process with polyvinylpyrrolidone (PVP) as an
      amphiphilic surfactant. The obtained NCs can be well dispersed in hydrophilic
      solutions with small sizes in the range of 9-12 nm. The LaF(3):Ln(3+) NCs (Ln =
      Eu, Nd, Ce, Tb, Yb, Er, Yb, Ho and Yb, Tm) have the unique feature of up-down
      conversion from visible to NIR emission owing to the ladder-like arranged energy
      levels of Ln(3+) and in particular, the high efficiency upconversion of the two
      photon, obtained from excitation by a continuous 980 nm laser. This investigation
      focuses on both the up and down conversion fluorescence properties of water
      soluble monodisperse crystalline LaF(3):Ln(3+) NCs in such a small size.
      Furthermore, the three-dimensional PDMS rod-like fluorescence displays and a
      silica surface modification by a core/shell structure on the obtained NCs can
      improve the biocompatibility, indicating potential applications in optical 3D
      devices and as bio-probes.

PMID- 23174760
TI  - Vaccination with embryonic stem cells generates effective antitumor immunity
      against ovarian cancer.
AB  - To date, only a few studies have suggested that human embryonic stem cells
      (hESCs) might effectively immunize against colon and lung cancer. The purpose of
      this study was to investigate the therapeutic potential of hESCs as a vaccine to
      induce widespread antitumor effects in different animal models and various types
      of cancer. C57BL/6 mice with ID8 ovarian cancer cell and Fischer 344 rats with
      NuTu-19 ovarian cancer cell models were used. Fifty-four mice were divided into
      six groups with nine mice in each group. Each mouse was immunized with pre
      inactivated hESCs (H9) or mouse embryonic stem cells (mESCs; IVP-ES1) or ID8 or
      phosphate-buffered saline (PBS). Twenty-four rats were divided into four groups
      with six rats in each group, each rat immunized with pre-inactivated hESCs (H9)
      or NuTu-19 or PBS. After the vaccination, each mouse was challenged with live ID8
      cells subcutaneously, and each rat was challenged with live NuTu-19 cells
      intraperitoneally. We discovered that vaccination of mice with the hESC line H9
      and the mESC line IVP-ES1 generated consistent cellular and humoral immune
      responses against ID8 ovarian cancer. H9 and IVP-ES1 vaccinated mice obtained
      antitumor immune protection, and H9 vaccinated rats had the longest survival time
      and least distant metastases. No evidence of side-effects was observed. We also
      compared the immunogenicity against ovarian cancer between the hESC line, H9, and
      the mESC line, IVP-ES1, that derived from the inner cell mass in different
      species. We found that there were no significant differences between them.
      Furthermore, immunohistochemical staining revealed that several oncogenes and
      tumor suppressor genes, such as HER-2, C-myc, p53, and nm23, were expressed in
      H9, many of which were also shared by ovarian cancer. hESC vaccines can induce
      antitumor effects in two animal models and in ovarian cancer, indicating that the
      activity of the vaccine is universal, and, more importantly, it is safe.

PMID- 23174761
TI  - Comment on "Origin of trisomy: no evidence to support the ovarian mosaicism
      theory".

PMID- 23174762
TI  - Comment on "Relationship of first-trimester uterine artery Doppler to late
      stillbirth".

PMID- 23174764
TI  - The virtual water content of major grain crops and virtual water flows between
      regions in China.
AB  - BACKGROUND: The disproportionate distribution of arable land and water resources
      has become a bottleneck for guaranteeing food security in China. Virtual water
      and virtual water trade theory have provided a potential solution to improve
      water resources management in agriculture and alleviate water crises in water
      scarce regions. The present study evaluates the green and blue virtual water
      content of wheat, maize and rice at the regional scale in China. It then assesses
      the water-saving benefits of virtual water flows related to the transfer of the
      three crops between regions. RESULTS: The national average virtual water content
      of wheat, maize and rice were 1071 m(3) per ton (50.98% green water, 49.02% blue
      water ), 830 m(3) per ton (76.27% green water, 23.73% blue water) and 1294 m(3)
      per ton (61.90% green water, 38.10% blue water), respectively. With the regional
      transfer of wheat, maize and rice, virtual water flows reached 30.08 Gm(3)
      (59.91% green water, 40.09% blue water). Meanwhile, China saved 11.47 Gm(3) green
      water, while it consumed 7.84 Gm(3) more blue water than with a no-grain transfer
      scenario in 2009. CONCLUSION: In order to guarantee food security in China, the
      government should improve water productivity (reduce virtual water content of
      crops) during the grain production process. Meanwhile, under the preconditions of
      economic feasibility and land-water resources availability, China should
      guarantee the grain-sown area in southern regions for taking full advantage of
      green water resources and to alleviate the pressure on water resources.

PMID- 23174765
TI  - How to pattern a leaf.
AB  - Leaf development presents a tremendous resource for tackling the question of
      patterning in biology. Leaves can be simple or highly dissected. They may have
      elaborated parts such as the tendrils of a pea leaf or the rolled blade of a
      carnivorous pitcher plant. Despite the variation in size, shape, and function,
      all leaves initiate in the same manner: from the flanks of a meristem. The maize
      leaf is useful for analysis of patterning due to the wealth of mutants and the
      distinct tissues along the proximal distal axis. The blade is distal, the sheath
      is proximal, and the ligule forms at the blade/sheath boundary. Establishment of
      this boundary involves the transcription factors LIGULELESS1 and LIGULELESS2 and
      the kinase LIGULELESS NARROW. The meristem-specific protein KNOTTED1 (KN1) binds
      and modulates the lg2 gene. Given the localization of KN1 at the proximal end of
      the leaf from the time of inception, we hypothesize that KN1 has a role in
      establishing the very proximal end of the leaf, whereas an auxin maximum guides
      the growing distal tip. 

PMID- 23174766
TI  - Stem cell signaling in immunity and development.
AB  - Stem cells in the shoot apical meristem (SAM) of plants are the self-renewable
      reservoir for leaf, stem, and flower organogenesis. Stem-cell fate and population
      size are subject to regulation by complex intrinsic signals and environmental
      cues to ensure balanced plant development, survival, and longevity. Peptides
      secreted from the shoot stem cells have pivotal roles in controlling cell
      identity, proliferation, and differentiation through multiple receptor kinase
      complexes. The best-characterized in vivo and in vitro peptide ligands are the 12
      amino acid (aa) and the arabinosylated 13-aa CLAVATA3 peptides (CLV3p) that are
      perceived by multiple receptors with partially overlapping and distinct
      expression patterns and functions in the SAM. The primary molecular and cellular
      signaling mechanisms after the occurrence of ligand-receptor interaction remain
      elusive. Integrated analyses provide novel evidence for differential peptide
      receptor signaling in the dynamic regulation of stem-cell homeostasis and
      fitness. Surprisingly, the 12-aa CLV3p can trigger immune signaling and limit
      pathogen invasion via the flagellin receptor kinase FLS2, suggesting a previously
      unrecognized molecular mechanism underlying enhanced immunity in the SAM area.
      Because pattern recognition receptor signaling in immune responses also
      profoundly intercepts plant development, peptide-receptor kinase signaling in
      immunity and development may share a common evolutionary origin. 

PMID- 23174767
TI  - Effector recognition and activation of the Arabidopsis thaliana NLR innate immune
      receptors.
AB  - Plant immunity to coevolved pathogens relies on the perception of pathogenic
      effectors by nucleotide-binding domain and leucine-rich repeat-containing (NLR)
      proteins-sophisticated intracellular receptors that have both perception and
      signaling roles in activating defenses. Given the conserved domain architecture
      of NLRs, a structural biology perspective is particularly relevant to
      understanding mechanisms of their activation. Here, we summarize our recent
      findings on the Arabidopsis resistance protein RPP1, a member of the TIR-NBS-LRR
      family of plant NLRs that specifically recognizes the cognate effector protein
      ATR1. To study the basis of RPP1 activation, we have taken advantage of a series
      of RPP1 and ATR1 alleles that differentially condition resistance. In planta
      association between the LRR domain of RPP1 and ATR1 only occurs in a resistance
      activating combination of alleles, suggesting that a direct interaction between
      RPP1 and ATR1 protein leads to activation of the NLR (Krasileva et al. 2010).
      Given critical amino acid residues' locations on the solved ATR1 crystal
      structure, and variable amino acid residues on the predicted LRR structure of
      RPP1, we hypothesize that specific "hotspots" of the horseshoe-like LRR fold
      mediate binding to the ATR1 ligand and that polymorphisms mapping to these
      surfaces condition differences in allelic recognition specificity. We present
      docking models of a possible co-complex between RPP1 and ATR1, and we propose
      that ATR1 binding relieves autoinhibition of RPP1 resistance signaling. This is
      consistent with current models of activation for both TIR- and CC-type plant
      NLRs, where conformational changes could lead to NLR oligomerization, nucleotide
      binding, translocation, and other critical downstream events in triggering
      immunity. 

PMID- 23174768
TI  - Effects of vaccination against reproductive diseases on reproductive performance
      of beef cows submitted to fixed-timed AI in Brazilian cow-calf operations.
AB  - The objectives were to assess incidence of pregnancy losses, associate this
      outcome with immunization programs against reproductive diseases, and evaluate
      the effects of vaccination against bovine herpesvirus-1 (BoHV-1), bovine viral
      diarrhea virus (BVDV), and Leptospira spp., on reproductive efficiency of
      Brazilian cow-calf operations. In experiment 1, 7614 lactating Nelore cows from
      18 ranches were assigned to the same estrus synchronization and fixed-time AI
      protocol (ESFTAI; Days -11 to 0). Pregnancy status was determined with
      transrectal ultrasonography on Days 30 and 120 after AI. Pregnancy loss was
      deemed to have occurred when cows were pregnant on Day 30 but nonpregnant on Day
      120. Incidence of pregnancy loss across all ranches was 4.1%; pregnancy losses
      were detected (P < 0.10) in 14 ranches but not detected (P > 0.11) in four
      ranches. Pregnancy loss was lower (P <= 0.02) in ranches that vaccinated against
      BoHV-1, BVDV, and Leptospira spp. compared with ranches that did not vaccinate,
      or only vaccinated against Leptospira spp. In experiments 2 and 3, lactating
      Nelore cows (N = 1950 and 2793, respectively) from ranches that did not have a
      history of vaccinating against reproductive diseases (experiment 2), or only
      vaccinated against Leptospira spp. (experiment 3), were assigned to the same
      ESFTAI used in experiment 1. Within each ranch, cows received (VAC) or not (CON)
      vaccination against BoHV-1, BVDV, and Leptospira spp. at the beginning of the
      ESFTAI (Day -11) and 30 days after (Day 41) AI. In experiment 2, VAC cows had
      greater (P <= 0.05) pregnancy rates compared with CON on Days 30 and 120. In
      experiments 2 and 3, pregnancy loss was reduced (P <= 0.03) in primiparous VAC
      cows compared with CON cohorts. In experiment 4, 367 primiparous, lactating
      Nelore cows previously vaccinated against Leptospira spp. were assigned to the
      same ESFTAI used in experiment 1. Cows received VAC, or the same vaccine 30 days
      before (Day -41) and at the beginning (Day -11) of the ESFTAI (PREVAC). Pregnancy
      rates on Days 30 and 120 were greater (P <= 0.05) in PREVAC cows compared with
      VAC cows. In conclusion, pregnancy losses affected reproductive and overall
      efficiency of Brazilian cow-calf operations, and might be directly associated
      with BoHV-1, BVDV, and Leptospira spp. infections. Hence, vaccinating cows
      against these pathogens, particularly when both doses are administered before
      fixed-time AI, improved reproductive performance in Brazilian cow-calf systems.

PMID- 23174769
TI  - Bovine oocytes show a higher tolerance to heat shock in the warm compared with
      the cold season of the year.
AB  - Heat stress is especially harmful for bovine ovarian follicle development and
      oocyte competence. In this study, we assessed the effects of heat shock on oocyte
      maturation in oocytes collected during the cold (February-March; n = 114) or warm
      (May-June; n = 116) periods of the year. In both cases, cumulus-oocyte complexes
      were matured under control (38  degrees C) and heat shock conditions (41.5 
      degrees C, 18-21 h of maturation). For each oocyte, nuclear stage, cortical
      granule distribution and steroidogenic activity of cumulus cells were evaluated.
      Based on the odds ratio, heat-shocked oocytes were 26.83 times more likely to
      show an anomalous metaphase II morphology. When matured under heat shock
      conditions, oocytes obtained in both seasons were similarly affected in terms of
      nuclear maturation, whereas a seasonal effect was observed on cytoplasmic
      maturation. For oocytes collected during the cold season, the likelihood to show
      an anomalous maturation was 25.96 times higher when exposed to the heat treatment
      than when matured under control conditions. By contrast, oocytes collected during
      the warm season matured under control or heat shock did not show significant risk
      of showing an anomalous cytoplasmic maturation. Our findings indicate an
      increased rate of premature oocytes in response to heat shock as well as a higher
      tolerance to this stress of oocytes harvested in the warm season compared with
      those collected in the colder period.

PMID- 23174770
TI  - Leptin and nonessential amino acids enhance porcine preimplantation embryo
      development in vitro by intracytoplasmic sperm injection.
AB  - Intracytoplasmic sperm injection (ICSI) has been considered one of the strong
      assisted reproductive technologies for producing transgenic animals as well as
      treating infertility in animals and humans. However, in porcine ICSI, embryos
      produced by in vitro methods show low pregnancy rates with high abnormal
      offspring and blastocyst formation rate as well as quality are poor compared with
      those in other species. For these reasons, developing a protocol for porcine ICSI
      is essential to efficiently generate transgenic pigs. Since amino acids were
      introduced to embryo development because of their beneficial effects, many
      embryologists have been using nonessential amino acid (NEAA) in culture medium
      for embryonic development in pig and other species. Leptin also has been shown to
      be beneficial in embryonic development for increasing rate of cleavage and
      blastocyst development. However, the effects of NEAA and leptin were not fully
      understood in the development of porcine ICSI-derived embryos. Here we
      investigated the optimization of NEAA and leptin supplementation in culture
      medium to improve developmental competence and quality of preimplantation embryos
      after ICSI in pig. The proportion of embryos that developed to the blastocyst
      stage was significantly greater when 1% vol/vol NEAA (24.6%) or 100 ng/mL leptin
      (27.1%) was supplemented in the culture medium compared with other concentrations
      or no supplement. When NEAA and leptin (24.8%) were supplemented together,
      blastocyst formation was significantly higher than other single supplementation
      groups. We also evaluated the effects of different supplementation periods of
      NEAA or leptin on the preimplantation embryonic development after ICSI. Both NEAA
      and leptin showed that supplementation for the entire 7 days significantly
      increased the blastocyst formation rate compared with the other groups of
      supplementation for the first 4 days and for the subsequent 3 days. A second goal
      of our research was to evaluate the quality of developed blastocysts after ICSI.
      The supplementation of 100 ng/mL leptin in culture medium made blastocysts
      express less of the proapoptosis genes BAX and BAK and more of the antiapoptosis
      genes BCL-XL and BCL-2 after the ICSI procedure. Furthermore, terminal
      deoxynucleotidyl transferase dUTP nick end labeling index, fragmentation, and
      total apoptosis were significantly decreased and the total cell number was
      significantly increased when the ICSI-derived embryos were cultured to blastocyst
      stage in the presence of the combination of NEAA and leptin. These results
      suggest that NEAA and leptin could improve not only the quantity but also quality
      of ICSI-derived porcine embryos during in vitro culture with the optimal
      concentration of each reagent.

PMID- 23174772
TI  - Occurrence and characteristics of residual follicles formed after transvaginal
      ultrasound-guided follicle aspiration in cattle.
AB  - Ultrasound-guided transvaginal follicle aspiration is used to recover cumulus
      oocyte complexes (for IVF) and to synchronize follicular wave emergence (ablation
      of dominant follicle). Although aspirated follicles are generally supposed to
      undergo immediate atresia, there are indications that they may remain active. The
      objective was to evaluate the occurrence and characteristics of residual
      follicles (RF) after transvaginal follicle aspiration in cattle. Ovarian
      follicular wave emergence was synchronized in Holstein cows (N = 13) in the
      presence (groups 1 and 3) or absence (groups 2 and 4) of norgestomet implants.
      The largest follicle was aspirated at a diameter of 8 mm (groups 1 and 2) or 12
      mm (groups 3 and 4). Ovarian follicles were visualized (transrectal
      ultrasonography) every 12 h after wave emergence. Follicular fluid samples were
      collected from the largest follicle and from the ensuing RF and concentrations of
      estradiol and progesterone were determined. After aspiration, 73.2% (52/71) of
      the follicles refilled with fluid, and a new antrum was detected 12 to 24 h
      later. Norgestomet did not affect (P > 0.05) RF occurrence or diameter, but in RF
      from group 4, concentrations of estradiol decreased (-530.7 +/- 133.9 ng/mL; P <
      0.01) whereas progesterone increased (+429.6 +/- 171.7 ng/mL; P < 0.05) relative
      to preaspiration. In RF, there were three steroidogenesis patterns: (1) high
      estradiol concentration and high estradiol:progesterone ratio (estradiol-active
      RF); (2) low estradiol, but high progesterone concentrations (luteinized RF); and
      (3) low estradiol and low progesterone concentrations (inactive RF). Estradiol
      active RF were more likely (P < 0.05) from follicles with high estradiol
      concentrations (regardless of diameter). In conclusion, fluid-filled structures
      (RF) with variable steroid production patterns are frequently formed after
      ultrasound-guided follicle aspiration. The occurrence and features of these RF
      depended on the diameter and status of these follicles before aspiration.

PMID- 23174771
TI  - A comparative study of the sperm nuclear morphometry in cattle, goat, sheep, and
      pigs using a new computer-assisted method (CASMA-F).
AB  - This study was designed to compare the sperm nuclear morphometry of four species
      of domestic artiodactyls (cattle, sheep, goats, and pigs), using the newly
      developed automatic computer-assisted sperm morphometry analysis-F. The study was
      divided into two experiments. In the first experiment, samples from 20 males from
      each species were collected, diluted, and divided into four sample aliquots. The
      first was labeled directly with Hoechst 33342, and the others were processed as
      smears. Between smears, one group was directly labeled with Hoechst after air
      drying, and the other was fixed either with glutaraldehyde (GLUT), or with
      methanol, and afterward labeled with Hoechst. Digital images of the fluorescence
      labeled sperm were recorded with a digital camera, and at least 200 sperm cells
      per sample were processed using the Image J analysis open software. Air-drying
      significantly reduced nuclear sperm dimensions in ruminant species, whereas no
      effect was observed in pigs. For most of the primary morphometric parameters, the
      relationship between the four species for the sperm nuclear dimensions can be
      described as follows: bull > ram >= boar > goat. However, ram sperm nuclei had
      greater width than those of the other species studied. For the secondary
      morphometric parameters, ram sperm nuclei were clearly less elliptical and
      elongated and showed greater regularity than in the other studied species. In the
      second experiment, ejaculates from 10 males per species were used to compare the
      sperm head morphometric results obtained with the computer-assisted sperm
      morphometry analysis-F system (using the GLUT treatment as reference) to a more
      conventional CASMA method (semen smears stained with Harris's hematoxylin and
      processed with the Integrated Sperm Analysis System [ISAS] commercial software
      [Proiser R&D SL, Bunol, Spain]). Spermatozoa displayed a bigger size when
      processed with Harris's hematoxylin than with the GLUT method in all primary
      sperm head morphometric parameters for the four species studied. A significant
      correlation was observed between the two methods used in this experiment for all
      morphometric size parameters in the four species studied. It was concluded that
      drying and fixation has little effect on sperm nuclear morphometry, with
      differences between species, and that there are significant variations in size of
      the sperm nucleus and in the hydrodynamic properties between the four species
      studied.

PMID- 23174773
TI  - Analysis of Sertoli cell efficiency allows the differentiation between two
      fundamentally different forms of feline teratospermia.
AB  - Teratospermia is a common phenomenon within felid species and has been attributed
      to reduction in genetic diversity. Testes from teratospermic domestic cats show
      enhanced spermatogenesis accompanied by remarkably reduced germ cell apoptosis.
      In the present study we investigated whether free-range teratospermic tom cats
      exhibit a similar testicular phenotype as proven permanently teratospermic males.
      Randomly collected teratospermic cats were compared with normal (normospermic;
      >60% morphologically normal sperm per ejaculate) and a well-characterized
      population of permanently teratospermic domestic cats, with respect to their
      spermatogenic potential. Histomorphologic assessment of testes from randomly
      collected teratospermic cats revealed no differences compared with normospermic
      donors. These two groups, however, were both different from permanently
      teratospermic cats, which exhibit fewer Sertoli cells and increased numbers of
      round spermatids per tubule cross-section resulting in a remarkably increased
      Sertoli cell efficiency (ratio of round spermatids to Sertoli cells). In
      conclusion, we can distinguish at least two fundamentally different forms of
      feline teratospermia. One subtype, found in most of the randomly collected tom
      cats, but not associated with altered quantitative spermatogenic parameters.
      Another subtype, found in all permanently teratospermic felids, is manifested by
      an impairment of Sertoli cell efficiency. We suggest that spermatogenic output
      should be analyzed before using random source domestic cats to study the
      phenomenon of teratospermia.

PMID- 23174774
TI  - Characterization of the carbonic anhydrases 15b expressed in PGCs during early
      zebrafish development.
AB  - The main function of carbonic anhydrases is to regulate acid-base balance. In the
      present study, the zebrafish CA15b sequence was identified from the National
      Center for Biotechnology Information database (accession No. NM_213182). The 1716
      base pair full-length cDNA of CA15b was obtained by 3' and 5'-rapid amplification
      of cDNA ends analysis. It was expressed (reverse transcription polymerase chain
      reaction and Western blot analysis) in the ovary, heart, brain, and muscle, but
      not in testis or liver. Based on in situ hybridization, CA15b mRNA was
      transcribed in the ooplasm of stage I to stage II oocytes, in the cortex of stage
      III oocytes, and along the periphery of stage IV oocytes. Furthermore, this
      protein was localized (immunohistochemistry) in the plasma membrane of oocytes.
      Based on whole-mount in situ hybridization, CA15b mRNA was present in every
      blastomere of embryos from one-cell to blastula stages. Strong signals of the
      transcripts were present along cleavage furrows of two- and eight-cell stage
      embryos, which subsequently condensed into four clusters of cells during the
      blastula stage. During subsequent stages, the four groups of CA15b-expressing
      cells appeared to move toward the dorsal side of the embryos, clustered into two
      groups on either side of the midline, and remained visible as they migrated
      toward the region of the gonad in embryos at 24 hours postfertilization.
      Expression patterns of CA15b were similar to those of vasa, a marker of
      primordial germ cells. Thus, we hypothesized that CA15b might be necessary for
      development of primordial germ cells and female germ cells in zebrafish.

PMID- 23174775
TI  - An evaluation of B-mode and color Doppler ultrasonography for detecting
      periovulatory events in the bitch.
AB  - When determining optimal breeding time in the bitch, specific periovulatory
      events must be identified. The main objectives were to relate ultrasonographic
      changes in ovarian blood flow, follicle/corpora lutea count and echotexture to
      periovulatory events, and to assess the efficacy of each for identifying these
      events. Twelve Beagle (N = 3), Beagle-cross (N = 2) and hound-cross (N = 7)
      bitches (body weight range, 7.5-27.5 kg) were examined daily from the onset of
      proestrus to approximately 4 days post-LH peak. Follicle and corpora lutea count
      and echotexture analyses were performed using B-mode ultrasound and ovarian blood
      flow analysis was performed using color Doppler ultrasound. Serum LH
      concentrations were analyzed by validated RIA. There was an increase (P < 0.05)
      in ovarian blood flow from the day of the preovulatory LH peak (605 pixels;
      confidence interval, 397-856), to 1 day after this peak (1092 pixels; confidence
      interval, 724-1535), enabling detection of the preovulatory LH peak. There were
      no significant changes in follicle/corpora lutea echotexture relative to days
      from the preovulatory LH peak. There were significant decreases in
      follicle/corpora lutea number between Days -1 and 3; Days -1 and 4; and Days 0
      and 3, relative to the preovulatory LH peak. We concluded that color Doppler
      ultrasound performed once daily was more accurate in identifying the preovulatory
      LH peak than B-mode ultrasound and enabled prospective determination of
      ovulation.

PMID- 23174776
TI  - Biopsy of embryos produced by in vitro fertilization affects development in
      C57BL/6 mouse strain.
AB  - Preimplantation genetic diagnosis is considered highly successful with respect to
      its accuracy in detecting genetic anomalies, although the effects of embryo
      biopsy on embryonic and fetal growth and development are less known, particularly
      in conjunction with IVF. Here, we compared biopsied (B) and nonbiopsied (NB)
      mouse embryos for developmental competence. Embryos C57BL/6 (B6) and B6D2F2 (F2)
      generated by IVF were subjected to single blastomere biopsy at the four-cell
      stage, and were either cultured for 120 h and subjected to differential inner
      cell mass (ICM) and trophoblast staining, or were transferred into the uterine
      tubes of surrogate mothers after 72 h of culture, to examine their pre- and
      postimplantation development, respectively. NB embryos from the same IVF cohorts
      served as controls. Embryo biopsy negatively affected preimplantation development
      to blastocyst in C57BL/6 (69% vs. 79%; P < 0.01), but not in B6D2F1 mice (89% vs.
      91%; P = not significant [NS]). Although B6 embryos had lower total cell number
      than F2 (B6: 47 and 61 vs. F2: 53 and 70; B and NB, respectively; P < 0.05) there
      were no differences between B and NB blastocysts in percentage of ICM (B6: 19.8
      vs. 19.8; F2: 20.9 vs. 20.4; P = NS) and ICM:trophoblast ratio (B6: 4.7 vs. 4.7;
      F2: 4.4 vs. 4.7) in both mouse strains. Postimplantation development to live
      fetuses of B embryos as compared with NB counterparts was impaired in C57BL/6 (6%
      vs. 18%; P < 0.001) but not in B6D2F1 mice (26% vs. 35%; P = NS). We concluded
      that blastomere biopsy impaired embryonic and fetal development in mice known to
      be sensitive to in vitro culture and manipulations. Such mice are models for
      infertile couples with poor quality gametes seeking assisted reproduction
      technologies.

PMID- 23174778
TI  - Production of myostatin-targeted goat by nuclear transfer from cultured adult
      somatic cells.
AB  - Myostatin, a member of the transforming growth factor-beta family, acts as a
      negative regulator of skeletal muscle mass. In this study, myostatin-targeted
      caprine fibroblasts were obtained and subjected to SCNT to determine whether
      myostatin-knockout goats could be created. Fibroblasts from a 2-mo-old goat were
      transfected with a myostatin-targeted vector to prepare transgenic donor cells
      for nuclear transfer. After serum-starvation (for synchronization of the cell
      cycle), the percentage of transgenic fibroblasts in the G(0)/G(1) phase increased
      (66.2% vs. 82.9%; P < 0.05) compared with that in the control group, whereas the
      apoptosis rate and mitochondrial membrane potential were unaffected (P > 0.05).
      There were no significant differences between in vivo- and in vitro-matured
      oocytes as recipient cytoplasts for rates of fusion (86.5% vs. 78.4%), pregnancy
      (21.6% vs. 16.7%), or kidding (2.7% vs. 0%). One female kid from an in vivo
      matured oocyte was born, but died a few hours later. Microsatellite analysis and
      polymerase chain reaction identification confirmed that this kid was genetically
      identical to the donor cells. Based on Western blot analysis, myostatin of the
      cloned kid was not expressed compared with that of nontransgenic kids. In
      conclusion, SCNT using myostatin-targeted 2-mo-old goat fibroblasts as donors has
      potential as a method for producing myostatin-targeted goats.

PMID- 23174777
TI  - Duration of gestation in pregnant dogs carrying cloned fetuses.
AB  - The aim of this study was to investigate gestation duration and the physiologic
      characteristics of pregnant dogs bearing cloned fetuses, especially in the
      prepartum period. A retrospective study was performed to compare gestation
      duration in females pregnant with cloned (somatic cell nuclear transfer) fetuses
      (cloned group) with those bearing noncloned fetuses (control group), and effects
      of litter size, birth weight, and breed of somatic cell donors on gestation
      duration in the cloned group were evaluated. Clinical delivery onset signs
      associated with serum progesterone concentration and rectal temperature were also
      compared in both groups. The gestation duration calculated from day of ovulation
      was significantly longer in the cloned (62.8 +/- 0.3 days) versus the control
      group (60.9 +/- 0.5 days; P < 0.001). There was a negative correlation between
      litter size and gestation duration including both groups (r = -0.59; P < 0.01),
      but there were no differences between birth weights or breed of cell donors and
      gestation duration in the cloned group. Even though the basal rectal temperature
      in the prepartum period was not different between control and cloned groups (36.9
      +/- 0.1  degrees C and 37.2 +/- 0.1  degrees C, respectively), serum progesterone
      concentration on delivery day was significantly higher in the cloned group (2.2
      +/- 0.4 ng/ml) compared with the control group (0.5 +/- 0.1 ng/ml; P < 0.05). The
      longer gestation duration of pregnant dogs bearing cloned fetuses might be
      because of the smaller litter size in this group. Also, the weaker drop in serum
      progesterone levels in the prepartum period in cloned dog pregnancies indicates
      that the parturition signaling process might be altered resulting in longer
      gestation periods.

PMID- 23174779
TI  - Possible involvement of Wnt/beta-catenin signaling pathway in hatching and
      trophectoderm differentiation of pig blastocysts.
AB  - The Wnt/beta-catenin signaling pathway plays essential roles in the regulation of
      cell fate and polarity during embryonic development of many animal species. This
      study investigated the possible involvement of Wnt/beta-catenin signaling pathway
      during hatching and trophectoderm (TE) development in pig blastocysts. Results
      showed that beta-catenin and DVL3, the key mediators of Wnt/beta-catenin
      signaling, disappeared from the nucleus after blastocyst hatching. Specific
      inhibition of Wnt/beta-catenin signaling pathway, by Dickkopf-1, increased the
      rate of blastocyst hatching, total nuclear number per blastocyst, and reduced the
      ratio of inner cell mass (ICM):TE (P < 0.05). In contrast, specific activation of
      the Wnt/beta-catenin signaling pathway, by lithium chloride, reduced the rate of
      blastocyst hatching, total nuclear number per blastocyst, and increased the ratio
      of ICM:TE (P < 0.05). The change in the ICM:TE ratio was associated with the
      change in the number of TE cells but not the ICM cells. Activation or inhibition
      of Wnt/beta-catenin signaling and beta-catenin nuclear accumulation, by lithium
      chloride or Dickkopf-1, also altered the expression of CDX2. These data
      therefore, suggest the possible involvement of Wnt/beta-catenin signaling in
      regulating hatching and TE fate during the development of pig blastocyst.

PMID- 23174780
TI  - Three-dimensional quantitative analysis of chromosomes in the oocytes of aging
      mice during meiosis I in vitro.
AB  - The mechanism of senescence is very complicated and can involve formation of
      chromosome abnormalities and a decline in female fertility. In this study, 3-D
      visualization of fluorescently labeled chromosomes in oocytes from aging and
      pubertal mice during in vitro maturation was done with a two-photon laser
      scanning microscope. Differences between aging and pubertal groups at various
      maturation stages were analyzed quantitatively in terms of chromosomal
      morphology, shape, and spatial arrangement. Compared with the pubertal group, the
      chromosomal morphology of oocytes from aging mice changed: both the mean volume
      and the mean surface area of chromosomes increased by approximately 20% (P <
      0.05) at prometaphase and metaphase of meiosis I (considered to be the weakly
      condensed folded form of the chromosomes). Furthermore, at these stages, the
      shape of the chromosomal array became rounder (roundness factor increased by
      approximately 10%; P < 0.001) and the adhesion among chromosomes became more
      severe (P < 0.001) at approximately the same stages. Additionally, trends over
      time for both chromosomal morphology and shape were quite distinct between
      oocytes from aging and pubertal mice. Interestingly, trends for mean distance
      were similar; therefore, aging did not seem to influence chromosome movement
      toward the metaphase plate. These morphologic results should be useful to study
      age-related degradation of oocyte quality and to interpret results derived from
      molecular biology.

PMID- 23174781
TI  - Resistin reduces mitochondria and induces hepatic steatosis in mice by the
      protein kinase C/protein kinase G/p65/PPAR gamma coactivator 1 alpha pathway.
AB  - Obesity is associated with many severe chronic diseases and deciphering its
      development and molecular mechanisms is necessary for promoting treatment.
      Previous studies have revealed that mitochondrial content is down-regulated in
      obesity, diabetes, and nonalcoholic fatty liver disease (NAFLD) and proposed that
      NAFLD and diabetes are mitochondrial diseases. However, the exact mechanisms
      underlying these processes remain unclear. In this study, we discovered that
      resistin down-regulated the content and activities of mitochondria, enhanced
      hepatic steatosis, and induced insulin resistance (IR) in mice. The time course
      indicated that the change in mitochondrial content was before the change in fat
      accumulation and development of insulin resistance. When the mitochondrial
      content was maintained, resistin did not stimulate hepatic fat accumulation. The
      present mutation study found that the residue Thr464 of the p65 subunit of
      nuclear factor kappa B was essential for regulating mitochondria. A proximity
      ligation assay revealed that resistin inactivated peroxisome proliferator
      activated receptor gamma coactivator 1 alpha (PGC-1alpha) and diminished the
      mitochondrial content by promoting the interaction of p65 and PGC-1alpha.
      Signaling-transduction analysis demonstrated that resistin down-regulated
      mitochondria by a novel protein kinase C/protein kinase G/p65/PGC-1alpha
      signaling pathway. CONCLUSION: Resistin induces hepatic steatosis through
      diminishing mitochondrial content. This reveals a novel pathway for mitochondrial
      regulation, and suggests that the maintenance of normal mitochondrial content
      could be a new strategy for treatment of obesity-associated diseases.

PMID- 23174782
TI  - [What about the diaphragm?].

PMID- 23174783
TI  - [Bacteriological study of bronchoalveolar lavage in the antibiotic management of
      suspected ventilator-associated pneumonia of patients in surgical intensive care
      units].
AB  - OBJECTIVE: To determine the correlation of Gram staining with the culture of
      bronchoalveolar lavage in patients with clinical features of ventilator
      associated pneumonia from two adult trauma and surgical intensive care units.
      METHODS: We conducted a retrospective study of 252 samples of bronchoalveolar
      lavage from patients with clinical ventilator-associated pneumonia in trauma or
      surgical postoperative care. Gram staining samples were classified as Gram
      positive cocci and Gram-negative bacilli, all other results being excluded.
      Cultures from bronchoalveolar lavage were compared with Gram staining results.
      RESULTS: The correlation between Gram staining and culture from the
      bronchoalveolar lavage showed a kappa index of 0.27. The sensitivity of Gram
      staining was 53.9% and the specificity, 80.6%. Considering the identification of
      Gram-positive cocci against other results (negative and Gram-negative bacilli),
      the negative predictive value was 94.8%. The evaluation of Gram-negative bacilli
      against other results (negative and Gram-positive cocci) rendered a sensitivity
      of 27.1% and a specificity of 95.4%. CONCLUSION: It appears that the negative
      predictive value for Gram-positive cocci is acceptable, but the sensitivity of
      Gram staining in the etiology of ventilator-associated pneumonia was not able to
      identify the microorganism before culture.

PMID- 23174784
TI  - Anthropometry and lipid profile in women with breast cancer: a case-control
      study.
AB  - OBJECTIVE: To assess body composition and lipid profile of women with and without
      breast cancer. METHODS: We conducted a case-control study matched by age,
      including 62 women, 31 being newly diagnosed with breast cancer and 31 with
      benign breast changes. Data were collected through direct interview, with
      recording of sociodemographic characteristics, body composition assessment by
      anthropometry, including skinfolds (DC) and circumference, bioelectrical
      impedance (BIA) and ultrasonography (USG), as well as lipid profile evaluation.
      STATISTICAL ANALYSIS USED: Kolmogorov-Smirnov test (normally distributed
      variables), "t" test, chi-square test for trend (Mann-Whitney U), chi-square
      test, Fisher's exact test and Yates correction and "odds ratio". RESULTS: When
      compared with controls, women with breast cancer (cases) had lower height (1.56 m
      +/- 5.68 versus 1.59 m +/- 6.92), p <0.03; higher percentage of body fat,
      assessed by Bioelectric Impedance (39.87% +/- 8.26 versus 36.00% +/- 6.85), p
      <0.049; and higher triceps skinfold thickness (27.55 mm +/- 8.37 versus 22.81 +/-
      5.72 mm; p <0.01), respectively. CONCLUSION: Women with breast cancer had lower
      height, higher body fat percentage and higher triceps skinfold thickness. There
      was no difference in body mass index and waist circumference. There was no
      association between lipid profile and the occurrence of breast cancer.

PMID- 23174785
TI  - [Anatomic and surgical study of the recurrent laryngeal nerve and its involvement
      with the ligament of Berry].
AB  - OBJECTIVE: To study the anatomical relations of the recurrent laryngeal nerve
      (RLN) with the ligament of Berry (LB), and point out the different ways of
      presenting the relationship between these two structures. METHODS: We conducted a
      study with anterior cervical dissection of 22 corpses, in the years 2009 and
      2010, with attention towards the frequency of presentation of anatomical
      relations between the NLR and Berry ligament, with the following classification:
      Type I or intraligamentary: the nerve and / or its branches were visualized in
      the ligament substance conjunctiva; Type IIA or lateral: nerve and / or its
      branches lateral to the ligament; Type IIB or lateral paraligamentary: nerve and
      / or its side branches and in contact with the ligament without penetrating it;
      Type III or medial: nerve and / or its branches visualized after complete
      dissection of the ligament, in lateral-medial position. RESULTS: The study
      analyzed 41 RLNs, which comprised eight (19.5%) of type I, 20 (48.8%) Type II,
      five (12.2%) Type IIB and eight (19.5%) type III. Of the 19 (86.3%) RLNs
      dissected bilaterally in the same cadaver, 11 (57.8%) displayed a classification
      in one side of the neck different from the one of the other side. CONCLUSION: Due
      to its proximity to the RLN and the anatomical variability, the Berry ligament
      should not be considered a reliable parameter for repair and preservation of the
      recurrent laryngeal nerve. Hence, the indiscriminate latero-medial dissection of
      the ligament is not recommended without direct visualization of the nerve.

PMID- 23174786
TI  - Use of triple-convergence polypropylene thread for the aesthetic correction of
      partial facial paralysis caused by the facial nerve injury.
AB  - OBJECTIVE: To evaluate the use of self-sustaining triple-convergence
      polypropylene thread for correction of hemiface deviation presenting as late
      result of facial paralysis. METHODS: We conducted a retrospective, observational
      study with 34 subjects with late facial paralysis. We used a triple-convergence
      polypropylene thread to correct the deviation of the paralyzed hemiface. It is a
      monofilament, synthetic, transparent and unabsorbable thread that has hooks that
      exert traction in the ptotic tissues, keeping them in the correct position, in
      symmetry with the healthy side. The results were evaluated by subjective
      analysis, with assessment of patient satisfaction with a proper questionnaire.
      RESULTS: We analyzed 34 patients, 73.52% of them reported great improvement,
      20.58% moderate improvement and 5.88%, slight improvement; we found a high
      satisfaction rate of 94.1%. Two patients had partial extrusion of the wire. No
      patient developed infection. CONCLUSION: The use of triple-convergence
      polypropylene thread to correct the deviation of hemiface consequent to facial
      palsy markedly improved facial asymmetry and recovery of patients' self-esteem.

PMID- 23174787
TI  - Evaluation of prevalence in the treatment of mandible condyle fractures.
AB  - OBJECTIVE: To study the treatment of fractures of the mandibular condyle and
      discuss conservative versus surgical therapy. METHODS: We examined the medical
      records of 892 bucofacial traumas, from which we selected only those who had:
      reports of condylar fractures, isolated or associated with other facial bones,
      identification data, dental care history and treatment applied for the condylar
      fracture. Data were analyzed using descriptive statistics, and the conservative
      and surgical therapies were compared. RESULTS: Condyle fractures were present in
      124 cases. Males represented 72.0% of the sample, the age group most affected
      being the one between 21 and 30 years. Conservative treatment was used in 61.0%
      of patients. CONCLUSION: Surgical treatment was predominantly used in patients
      over ten years old, victims of traffic accidents and falls, followed by assaults,
      firearms and sporting accidents.

PMID- 23174788
TI  - Comparison of survival and prognostic factors in patients with gastric
      adenocarcinoma in T2 and T3.
AB  - OBJECTIVE: To compare the survival and prognosis after surgical treatment of
      patients with gastric adenocarcinoma which extends to the muscular layer (T2),
      and patients whose tumor invades the subserosa (T3). METHODS: This was a
      retrospective study of 122 patients with gastric cancer invading the muscularis
      propria and subserosa, undergoing surgical treatment from January 1997 to
      December 2008 and followed-up until December 2010. We analyzed demographic,
      surgical and pathological variables. RESULTS: Of the 122 patients, 22 (18%) were
      excluded from the final analysis because they showed: positive margin or less
      than 15 lymph nodes in the surgical specimen, early postoperative mortality and
      second primary tumors. Among the 100 patients included, 75 had tumors inveding
      the muscularis propria (T2) and 25 with extension to the subserosa (T3). Overall
      survival was 83.8%, and 90.6% for T2 and 52.1% or T3. Univariate analysis showed
      statistical significance in: lymph node metastasis (p = 0.02), tumor size (p =
      0.000), tumor pathological stage (p = 0.000), lymph node pathologic stage (p =
      0.000) and staging by classification of groups TNM-UICC/AJCC, 2010 (p = 0.000).
      In multivariate analysis, independent prognostic factors were tumor size and
      lymph node pathological staging (pN). CONCLUSION: The lymph node status and tumor
      size are independent prognostic factors in tumors with invasion of the muscularis
      propria and in tumors with invasion of subserosa. T2 lesions have smaller size,
      lower rate of lymph node metastasis and therefore better prognosis than T3.

PMID- 23174789
TI  - Severe acute pancreatitis: results of treatment.
AB  - OBJECTIVE: To evaluate the results of the Protocol for treatment of patients with
      severe acute pancreatitis. METHODS: We consecutively analyzed age, gender,
      etiology, length of hospital stay, type of treatment and mortality of 37 patients
      with severe acute pancreatitis from January 2002. RESULTS: The patients' ages
      ranged from 20 to 88 years (average 50 years), 27% were female and 73% male. Mean
      overall hospital stay was 47 days. Thirteen patients were treated surgically, the
      average operations per patient was two. There were six deaths among patients
      undergoing surgical treatment (46%) and two deaths in the group submitted to
      medical treatment alone (8.3%). The overall mortality was 21%. CONCLUSION: After
      modification in the form of management of patients with severe acute
      pancreatitis, there was a decrease in mortality and a trend for conservative
      management.

PMID- 23174790
TI  - [Morbidity and mortality associated to loop colostomy and ileostomy closure].
AB  - OBJECTIVE: To evaluate the morbidity and mortality of operations for closure of
      loop colostomies and ileostomies. METHODS: We analyzed epidemiological data,
      postoperative complications, morbidity and mortality of patients who underwent
      operations for closure of loop colostomies and ileostomies. We excluded patients
      whose data could not be obtained from the files and operations that required
      laparotomy for closure. RESULTS: 88 patients were operated on, five being
      excluded. We evaluated the data of 83 patients, 56 patients with colostomies
      (group C) and 27 with ileostomies (group I). Males predominated in both groups (C
      = 71.9% and I = 57.7%). In group C the most common indication for making the
      stoma was abdominal trauma (43.9%) and in group I it was protecting a colorectal
      anastomosis (57.6%). The rate of anastomotic dehiscence in group C was 3.5% and
      in group I 19.2%. Morbidity was higher in group I than in group C (30.7% vs.
      12.2%). There was one death in group I. CONCLUSION: The study suggests that
      morbidity associated with stoma closure is high, being higher in patients with
      loop ileostomy.

PMID- 23174791
TI  - Superficial papillary urothelial neoplasms of the bladder (PTA E PT1):
      correlation of expression of P53, KI-67 and CK20 with histologic grade,
      recurrence and tumor progression.
AB  - OBJECTIVE: To investigate the immunohistochemical expressions of p53, ki67, CK20
      in superficial papillary urothelial neoplasms of the bladder and correlate them
      with histological grade, tumor progression and recurrence. METHODS: We selected
      samples of 43 patients with superficial transitional cell carcinoma of the
      bladder. They were divided into two groups, one called Recurrent (R), with 18
      individuals, and other Non-Recurrent (NR), with 25. Multi-sampling blocks were
      prepared. The immunohistochemical technique employed was immunoperoxidase, and
      the antibodies were: p53: Novocastra (clone DO7) at a dilution of 1/100; Ki67:
      Spring (clone SP6) at a dilution of 1/100; and CK20: Dako (clone K20 .8) at a
      dilution of 1/50. RESULTS: The expression of p53 was observed in 11 cases, six in
      the Recurrent group and five in the Non-Recurrent, all high-grade tumors (p =
      0.0001). The histological progression occurred in six patients (p = 0.0076). Of
      the 18 Recurrent cases, six showed immunoreactivity for p53 and 12 were negative
      for this antibody (p = 0.1715). Ki67 was positive in 17 of the 18 cases from the
      Recurrent group (p = 0.0001) and, from 20 high-grade tumors, 18 showed reaction
      to this antibody (p = 0.0001). Of the 18 individuals who had recurrence, 13
      showed anomalous expression for CK20 (p = 0.0166). In high-grade carcinomas, of
      the 20 cases, 16 showed anomalous expression for this antibody, while 18 of the
      23 patients with low-grade tumors showed normal expression for CK20 (p = 0.0002).
      CONCLUSION: The p53 showed good correlation with histological progression and
      histologic grade. Ki67 was strongly associated with recurrence and histological
      grade, and CK20 was also associated with these variables.

PMID- 23174792
TI  - Vitamin D and skin repair: a prospective, double-blind and placebo controlled
      study in the healing of leg ulcers.
AB  - OBJECTIVE: To analyze the relation between vitamin D insufficiency and wound
      healing in patients with venous ulcers; to correlate vitamin D insufficiency with
      characteristics of the ulcer (size and pain) and to evaluate if reposition of
      vitamin D in these subjects expedites ulcer healing. METHODS: We selected 26
      patients with leg ulcers, and 26 control patients without ulcers, matched for
      gender, age, systemic arterial hypertension and tobacco use. The venous ulcer
      group was divided in two subgroups: one that received placebo (nine patients) and
      other receiving vitamin D, 50.000 IU per week over two months (13 patients).
      Blood was collected for 25 OH vitamin D dosage before and after the medication.
      In the ulcer group, we obtained data concerning demographics, leg ulcer size, as
      well as pain severity, measured by an analogical visual scale. Data was grouped
      in contingency and frequency tables, the tests of Fisher and chi-squared being
      used for nominal variables and Mann-Whitney for numerical variables. The adopted
      significance was of 5%. RESULTS: We found vitamin D insufficiency in the great
      majority of the patients. The median level in the ulcer group was 17.05 ng/dl and
      22.75 ng/dl in the group without ulcer (p=0,0182) No relation was found between
      the ulcer size without treatment and the level of vitamin D. After treatment, the
      average size of the ulcer changed from 25 cm2 to 18 cm2 in the patients that took
      vitamin D and from 27 cm2 to 24,5 cm2 in the placebo group (p=0,7051 and
      p=0,7877, respectively). Considering the variability of the size of the ulcer in
      the treatment group versus placebo group, the average size was equal to -0,75 cm2
      in the first group and +4cm2 in the second (p=0,0676) CONCLUSION: Patients with
      leg ulcers have more vitamin D deficiency. No difference in the ulcer
      characteristics was noted between those with and without vitamin D deficiency.
      There was a trend toward a better healing in those with vitamin D reposition.

PMID- 23174793
TI  - [Echoendoscopy in digestive subepithelial lesions: review of the literature].
AB  - Injury or bulging subepithelial mucosal lesions are covered with normal mucosa,
      usually asymptomatic. Most are diagnosed in radiology or endoscopy, which may
      correspond to any layer of the body wall (intramural) or non-belonging to the
      wall (extramural). This article describes studies for analysis of endoscopic
      ultrasonography (EUS) as a diagnostic method with high accuracy on the finding of
      subepithelial lesion. The authors review the literature on the endoscopic
      ultrasound features of subepithelial lesions and differentiation in intra-or
      extramural, source layer, echogenicity, vascularity, size and margins, fine
      needle aspiration (FNA) and needle biopsies of type "trucut" for histological
      analysis. The EUS has the best combination of accuracy in the diagnosis of
      gastrointestinal wall layer compromised by lesions or masses, besides studying
      the echogenicity of the lesion, which helps in differential diagnosis. EUS is
      safe and detailed, considered the best imaging for definitive diagnosis and
      therapeutic planning of subepithelial lesions.

PMID- 23174794
TI  - [Rational use of animal models for research and microsurgery training].
AB  - The objective of this study is to disclose an experimental model of low cost,
      which complies with the regulatory norms of animal experiments by using dead
      animals from other experiments, contributing to the improvement of microsurgery
      learning. Cadavers of Wistar rats, originated from disposal of other courses, are
      used. The corpses of thawed mice are used for basic microsurgical training of
      medical students at the Nove de Julho University, aiming to contribute to the
      students' training. Their use is justified by the low cost of the material used,
      many animals being spared during the intermediate phase of skill development for
      realization of micro-anastomoses. This experimental model is inexpensive and
      allows the rational use of animals, corroborating with the ethical standards of
      experimental research and contributing to the education and training of
      microsurgery.

PMID- 23174796
TI  - [Citing of national articles: the (de)valuation of Brazilian journals].
AB  - OBJECTIVE: To evaluate whether there is a preference for foreign periodicals over
      Brazilian one. METHODS: We evaluated all references of articles published in the
      years 2011 and 2007 in the journals Acta Cirurgica Brasileira, Arquivos
      Brasileiros de Cirurgia Digestiva and the Journal of the Brazilian College of
      Surgeons, verifying the quantity of papers from Brazilian and foreign
      publications. RESULTS: We analyzed a total of 7,343 references arranged in 348
      articles in those three journals; of these, 856 (11.65%) were from Brazilian
      journals. There was no difference between the three magazines, nor between the
      two periods. One hundred and eleven (31.9%) articles did not cite any Brazilian
      journal article and 36 (10.34%) cited Brazilian articles more than foreign ones.
      CONCLUSION: There is need for the Brazilian researcher to appreciate more the
      Brazilian journals, increasing citation from Brazil, without a scientific
      xenophobia.

PMID- 23174795
TI  - [Transhiatal esophagectomiy using partial sternotomy].
AB  - Transhiatal Esophagectomy offers the advantage of not requiring thoracotomy or
      thoracoscopy. Nevertheless, it has the disadvantage of having to be performed, at
      least in part, with blind, blunt dissection, with high frequency of pleural
      lesions, increased bleeding, among other complications. The association of median
      diaphragm transection with partial sternotomy allows the isolation of the
      esophagus completely under direct vision. The authors present the technique of
      transhiatal esophagectomy with partial sternotomy.

PMID- 23174797
TI  - [Videosurgery in infancy and childhood: state of the art. Experience with 1408
      procedures in the Instituto da Crianca "Pedro de Alcantara"].
AB  - The videosurgery in Pediatric Surgery has a large field of applications
      unfortunately still underexplored. There are few services that routinely use this
      techinic , and Brazilian articles published are scarce. The Institute of
      Children's Hospital of the Faculty of Medicine, University of Sao Paulo, has been
      using for fifteen years the videosurgery which is now the first choice of
      treatment, among other diseases as gastroesophageal reflux, the
      cholecystolithiasis, the nonpalpable undescended testicles and megaesophagus. In
      this article we report our experience in laparoscopic pediatric surgery, acquired
      with 1408 surgical procedures, to present this useful method, and beneficial to a
      large number of situations and still underused in Pediatric Surgery.

PMID- 23174798
TI  - Uncomplicated acute cholecystitis: early or delayed laparoscopic cholecystectomy?
AB  - Recent meta-analyses suggested that early laparoscopic cholecystectomy (within 1
      week of symptom onset) for uncomplicated acute gallbladder disease is safe and
      feasible. However, surveys on surgical practices indicated that early
      laparoscopic cholecystectomy is performed by only a minority of surgeons.
      Furthermore, the exact time-point for performing this procedure as well as its
      cost-effectiveness remain a matter of debate. The TBE - CiTE Journal Club
      performed a critical appraisal of the most relevant evidence recently published
      on timing of laparoscopic cholecystectomy and its cost-effectiveness for the
      management of uncomplicated acute cholecystitis and provides evidence-based
      recommendations on the topic. The literature encompasses small trials with high
      risk of biases. It suggests that early laparoscopic cholecystectomy is safe and
      shortens hospital stay. There is scarcity of well-designed and large cost-utility
      analyses. The following main recommendations were generated: (1) Early
      laparoscopic cholecystectomy should be attempted as the first-line treatment
      within one week of symptoms onset; and (2) The cost-effectiveness of early
      laparoscopic cholecystectomy should be evaluated at the individual hospital
      level, taking into consideration local resources such as the availability of
      trained personal, operating room and laparoscopic equipment.

PMID- 23174799
TI  - [Primary synovial sarcoma of the esophagus].
AB  - Synovial sarcomas are uncommon malignant mesenchymal tumors occurring mainly near
      the joints of the extremities of young adults. Synovial sarcomas are exceedingly
      rare neoplasms of the digestive tract. We report the first diagnosed case of
      esophageal synovial sarcoma, highlighting its diagnostic features surgical
      management and follow-up.

PMID- 23174800
TI  - [Human bone fragment acting as a secondary projectile set off by an explosion].
AB  - We report a case of a secondary projectile emanated from a fractured human bone
      from a victim of a bomb explosion. We also refer to the potential of transmition
      of blood-borne or body fluid pathogens by this mechanism of injury.

PMID- 23174801
TI  - "Trust is not something you can reclaim easily": patenting in the field of direct
      to-consumer genetic testing.
AB  - PURPOSE: Recently, 23andMe announced that it had obtained its first patent,
      related to "polymorphisms associated with Parkinson's disease" (US-B-8187811).
      This announcement immediately sparked controversy in the community of 23andMe
      users and research participants, especially with regard to issues of transparency
      and trust. The purpose of this article was to analyze the patent portfolio of
      this prominent direct-to-consumer genetic testing company and discuss the
      potential ethical implications of patenting in this field for public
      participation in Web-based genetic research. METHODS: We searched the publicly
      accessible patent database Espacenet as well as the commercially available
      database Micropatent for published patents and patent applications of 23andMe.
      RESULTS: Six patent families were identified for 23andMe. These included patent
      applications related to: genetic comparisons between grandparents and
      grandchildren, family inheritance, genome sharing, processing data from
      genotyping chips, gamete donor selection based on genetic calculations, finding
      relatives in a database, and polymorphisms associated with Parkinson disease.
      CONCLUSION: An important lesson to be drawn from this ongoing controversy seems
      to be that any (private or public) organization involved in research that relies
      on human participation, whether by providing information, body material, or both,
      needs to be transparent, not only about its research goals but also about its
      strategies and policies regarding commercialization.

PMID- 23174803
TI  - Directed organization of gold nanoparticles in polymer coatings through infrared
      assisted evaporative lithography.
AB  - Infrared-assisted evaporative lithography (IRAEL) is presented as an emerging
      technology to direct the assembly of gold nanospheres (AuNSs) into large-scale
      superstructures within colloidal polymeric coatings. The organization of gold
      nanoparticle arrays within the superstructures can be tuned over length scales,
      ranging from micrometers up to several millimetres, giving rise to intrinsic
      plasmonic properties.

PMID- 23174802
TI  - Wenxin Keli attenuates ischemia-induced ventricular arrhythmias in rats:
      Involvement of L-type calcium and transient outward potassium currents.
AB  - Wenxin Keli is the first state-sanctioned traditional Chinese medicine (TCM)
      based antiarrhythmic drug. The present study aimed to examine whether long-term
      treatment with Wenxin Keli reduces ischemia-induced ventricular arrhythmias in
      rats in vivo, and if so, which mechanisms are involved. Male rats were treated
      with either saline (control group) or Wenxin Keli for 3 weeks and were subjected
      to myocardial ischemia for 30 min with assessment of the resulting ventricular
      arrhythmias. The L-type calcium current (ICa,L) and transient outward potassium
      current (Ito) were measured by the patch clamp technique in normal rat cardiac
      ventricular myocytes. During the 30-min ischemia, Wenxin Keli significantly
      reduced the incidence of ventricular fibrillation (VF) (P<0.05). The number of
      ventricular tachycardia (VT)+VF episodes and the severity of arrhythmias were
      significantly reduced by Wenxin Keli administration compared to the control group
      (P<0.05). In addition, Wenxin Keli inhibited ICa,L and Ito in a concentration
      dependent manner. These results suggest that long-term treatment with Wenxin Keli
      may attenuate ischemia-induced ventricular arrhythmias in rats and that ICa,L and
      Ito may be involved in this attenuation.

PMID- 23174804
TI  - Chronic intermittent hypoxia aggravates intrahepatic endothelial dysfunction in
      cirrhotic rats.
AB  - Chronic intermittent hypoxia (CIH) occurs with obstructive sleep apnea syndrome
      (OSAS) and provokes systemic endothelial dysfunction, which is associated with
      oxidative stress and low nitric oxide (NO) bioavailability. Cirrhotic livers
      exhibit intrahepatic endothelial dysfunction, which is characterized by an
      impaired endothelium-dependent response to vasodilators and hyperresponse to
      vasoconstrictors. We hypothesized that CIH may also contribute to intrahepatic
      endothelial dysfunction in cirrhosis. Normal and cirrhotic rats were exposed for
      14 days to repetitive cycles of CIH mimicking OSAS in humans, or caged with room
      air (handled controls [HC]). Hepatic endothelial function was assessed in
      isolated and perfused rat livers by dose-response curves to acetylcholine (ACh)
      and methoxamine (Mtx). In a group of cirrhotic rats, in vivo systemic and hepatic
      hemodynamic parameters were evaluated at baseline and after volume expansion. In
      addition, liver samples were obtained to assess endothelial nitric oxide synthase
      (eNOS), phosphorylated eNOS (p-eNOS), NO bioavailability, and nitrotyrosinated
      proteins as a marker of oxidative stress. Cirrhotic rats exposed to CIH exhibited
      an attenuated vasodilatory response to ACh and hyperresponse to Mtx compared with
      HC rats. During volume expansion, similar portal pressure increases were observed
      in CIH and HC rats, although the mean arterial pressure increase was lower after
      CIH. These functional responses were associated with the presence of increased
      hepatic oxidative stress without changes in p-eNOS after CIH exposure. In normal
      rats, no hemodynamic changes were found. CONCLUSION: CIH exacerbates intrahepatic
      endothelial dysfunction in cirrhotic rats, which is associated with increased
      oxidative stress that may reduce NO bioavailability. Clinical studies are needed
      to assess whether OSAS contributes to endothelial impairment in human patients
      with cirrhosis.

PMID- 23174805
TI  - Step-wise kinetics of natural physical ageing in arsenic selenide glasses.
AB  - The long-term kinetics of physical ageing at ambient temperature is  studied in
      Se-rich As-Se glasses using the conventional differential scanning calorimetry
      technique. It is analysed through the changes in the structural relaxation
      parameters occurring during the glass-to-supercooled liquid transition in the
      heating mode. Along with the time dependences of the glass transition temperature
      (T(g)) and partial area (A) under the endothermic relaxation peak, the enthalpy
      losses (DeltaH) and calculated fictive temperature (T(F)) are analysed as key
      parameters, characterizing the kinetics of physical ageing. The latter is shown
      to have step-wise character, revealing some kinds of subsequent plateaus and
      steep regions. A phenomenological description of physical ageing in the
      investigated glasses is proposed on the basis of an alignment-shrinkage mechanism
      and first-order kinetic equations.

PMID- 23174806
TI  - Healing a community by innovating at a community health center.
AB  - Somava Stout led care transformation at a Boston-area clinic and now spearheads
      implementation of the patient-centered medical home model at the Cambridge Health
      Alliance.

PMID- 23174807
TI  - Using digital communications and social media to redraw the cardiac care map.
AB  - Emergency medicine physician Raina Merchant created a cell phone program to
      provide CPR instructions-and now leads an effort to map every automated external
      defibrillator in the United States.

PMID- 23174808
TI  - Promoting health and development in detroit through gardens and urban
      agriculture.
AB  - The city's community gardens today supply just 2 percent of the fruit and
      vegetables consumed locally. Ashley Atkinson aims for "food sovereignty"-the day
      when most of the fresh fruits and vegetables that city residents eat are also
      grown there.

PMID- 23174809
TI  - Applying data analytics and information exchange to improve care for patients.
AB  - Parkland Hospital's Ruben Amarasingham built a model to predict patients at high
      risk for readmission and now leads efforts to extend the benefits of health
      information to the nation's most vulnerable.

PMID- 23174810
TI  - Understanding the health impact of racism--and trying to reverse it.
AB  - Naa Oyo Kwate not only explores the health impact of racism and inequality, but
      she also seeks to improve health through innovative "countermarketing" efforts
      against racism.

PMID- 23174811
TI  - Creating a new model to help health care providers write prescriptions for
      health.
AB  - Rebecca Onie and a colleague founded Health Leads, an organization staffed by
      student advocates who help doctors and other health care providers "prescribe"
      basic resources such as food and heat.

PMID- 23174812
TI  - Drawing on community organizing to advance public health in Minnesota and beyond.
AB  - As leader of a faith-based organization in Minnesota, Doran Schrantz has worked
      for transit, housing, and other policies to benefit the health of low-income
      people.

PMID- 23174814
TI  - Bringing the concepts of peer coaches and local health workers from Africa to
      Harlem.
AB  - Prabhjot Singh, a PhD scientist and medical resident, saw the effectiveness of
      community health workers while working in Africa. Now he helps run a New York
      based organization that trains peer coaches to help struggling Americans manage
      their health.

PMID- 23174813
TI  - Bucking conventional wisdom and focusing on disparities to address kidney
      disease.
AB  - Physician and clinical researcher Carmen A. Peralta devised a breakthrough
      testing strategy for detecting those at risk of developing end-stage renal
      disease-a condition that afflicts disproportionate numbers of blacks and
      Hispanics.

PMID- 23174815
TI  - Employing behavioral economics and decision science in crucial choices at end of
      life.
AB  - A program created by physician Scott Halpern employs multidisciplinary teams to
      help patients and family members make end-of-life decisions that track with their
      goals.

PMID- 23174816
TI  - CO2 superabsorption in a paddlewheel-type Ru dimer chain compound: gate-open
      performance dependent on inter-chain interactions.
AB  - A porous one-dimensional coordination chain compound, [Ru(2)(p-F
      PhCO(2))(4)(phz)] (; p-F-PhCO(2)(-) = para-fluorobenzoate; phz = phenazine)
      derived by drying its nitrobenzene-solvated compound, specifically adsorbs CO(2)
      at 195 K in a stepwise sorption manner.

PMID- 23174817
TI  - A diastereoselective synthesis of pyrano fused coumarins via organocatalytic
      three-component reaction.
AB  - A new method for the synthesis of pyran fused coumarins by 3-bromo-4
      hydroxycoumarins as cyclic alpha-halo ketones based on an organocatalyst assisted
      three-component tandem reaction is investigated. To the best of our knowledge,
      cyclic alpha-halo ketones have not yet been used for the synthesis of pyran fused
      coumarins.

PMID- 23174818
TI  - Glycosylated copper(II) ionophores as prodrugs for beta-glucosidase activation in
      targeted cancer therapy.
AB  - 8-Hydroxyquinoline derivatives are metal-binding compounds that have recently
      attracted interest as therapeutic agents for cancer therapy. In this scenario, we
      designed and synthesized three new glucoconjugates, 5,7-dichloro-8-quinolinyl
      beta-D-glucopyranoside, 5-chloro-8-quinolinyl-beta-D-glucopyranoside and 2-methyl
      8-quinolinyl-beta-D-glucopyranoside and investigated their biological properties
      in comparison to the parent 8-hydroxyquinoline derivatives in the presence of
      Cu(2+). In vitro data show that 2 out of 3 glycosylated compounds possess a
      pharmacologically-relevant antiproliferative activity against tumor cells,
      similar to that of their parent compounds; this activity is associated with a
      relevant triggering of apoptosis. The pharmacological profile of the
      glucoconjugates depends on the cellular enzymatic beta-glucosidase activity, as
      demonstrated by the inhibition of antiproliferative activity in the presence of
      the 2,5-dideoxy-2,5-imino-D-mannitol.

PMID- 23174819
TI  - MiR-21 regulates biological behavior through the PTEN/PI-3 K/Akt signaling
      pathway in human colorectal cancer cells.
AB  - The aim of this study was to determine a role of microRNA-21 (miR-21) in
      colorectal cancer (CRC) and to elucidate the regulation of phosphatase and tensin
      homologue (PTEN) gene by miR-21. MiR-21 expression was investigated in 30 CRC
      samples and five CRC cell lines. In this study, we show that the expression of
      miR-21 was overexpressed in CRC compared with adenomas and normal tissues.
      Patients with poor differentiation, lymph node metastasis and advanced TNM stage
      showed significantly high expression of miR-21. Inhibition of miR-21 in the
      HCT116 cell line reduced cellular proliferation, migration and invasion, induced
      apoptosis and inhibited cell cycle progression. The PTEN protein levels in CRC
      tissues and cells had an inverse correlation with miR-21 expression. Anti-miR-21
      transfected cells increased PTEN protein expression without changing the PTEN
      mRNA level and increased a luciferase-reporter activity. MiR-21 targets PTEN at
      the post-transcriptional level and regulates cell proliferation and invasion in
      CRC. It may serve as a novel therapeutic target in CRC.

PMID- 23174820
TI  - Exploring clinical and personality characteristics of adult male internet-only
      child pornography offenders.
AB  - Despite the dramatic increase in the number of convicted child pornography
      offenders, little is known about their potential clinical needs. The few studies
      that do explore this subgroup of sex offenders suggest clinical heterogeneity
      compared with other sex offender subgroups. However, research designs used in
      many studies have limited generalizability, have examined primarily treated or
      treatment samples, and have not included comparisons with nontreatment, community
      samples of men. The current study addresses such limitations by using
      nontreatment samples and multiple comparison groups to examine mean scales score
      differences on a commonly used clinical and personality assessment, the
      Personality Assessment Inventory (PAI). The sample, drawn from an admissions
      cohort of federal offenders, those Internet-only Child Pornography Offenders
      (ICPOs; n = 35) and those with a history of child molesting exclusively (child
      molesters, n = 26). They were compared with each other and the male normative
      sample from the PAI. Results indicate that interpersonal deficits and depression
      featured most prominently in the profiles of the ICPOs. Consistent with prior
      research, they also obtained lower scores on aggression and dominance compared
      with the child molesters and the male normative sample. Implications for future
      research, training, and clinical practice with incarcerated ICPOs are offered. 

PMID- 23174821
TI  - Identifying risk factors for victimization among male prisoners in Taiwan.
AB  - This study identified risk factors for prison victimization in Taiwan with an
      application of Western literature and assessed the extent of its applicability in
      an Eastern context. The sample was drawn from four male prisons located in
      Northern, Central, Southern, and Eastern Taiwan; a total of 1,181 valid surveys
      were collected. The results generally support the major findings of the extant
      Western studies. Crowding, however, was not significantly associated with the
      risk of victimization in any of the statistical models, which might be related to
      the different experiences and living conditions in the free community between
      Taiwanese and American inmates. This study generated clear policy implications,
      which may reduce prison victimization and engender a greater sense of well-being
      in the prison environment. 

PMID- 23174822
TI  - SEM-EDX, water absorption, and wetting capability studies on evaluation of the
      influence of nano-zinc oxide as additive to paraloid B72 solutions used for
      wooden artifacts consolidation.
AB  - Consolidation of frail, degraded wood is a key issue of wooden cultural heritage
      conservation. Paraloid B72 is one of the most often used consolidant in
      conservation practice. The present research aimed at formulating stable
      consolidation solutions of Paraloid B72 with ZnO nano-additives and at
      determining the influence of these additives on the penetration pathways,
      retention of the consolidation material into wood and on the water behavior of
      the treated wood. The experiments were performed on sound samples of aspen
      (Populus tremula). The addition of nano-ZnO slightly increased the uptake and
      retention of the consolidant within the wooden structure and led to hydrophobic
      surfaces. However, the influence of nano-ZnO additives to the water absorption
      was not conclusive. Scanning Electron Microscope coupled with an EDX Detector
      investigation proved vessels, fibers, and interconnecting pits as main pathways
      of consolidant penetration into the wooden structure as well as the presence and
      distribution of nano-ZnO.

PMID- 23174823
TI  - Dexamethasone induces rapid promotion of norepinephrine-mediated vascular smooth
      muscle cell contraction.
AB  - The aim of the present study was to identify the rapid effect of dexamethasone
      (Dex) on norepinephrine (NE)-mediated contraction of vascular smooth muscle cells
      (VSMCs) and to establish the underlying mechanism(s). Rat VSMCs were preincubated
      with lipopolysaccharide to simulate acute septic shock. Myosin light chain
      (MLC20) phosphorylation of VSMCs was detected by western blot analysis to observe
      the effects of Dex on NE-mediated contraction. Activation of the RhoA/ RhoA
      kinase (ROCK), extracellular signal-regulated kinase (ERK) and p38 signaling
      pathways was detected by western blot analysis to explore the mechanism. It was
      identified that Dex rapidly promoted NE-induced phosphorylation of MLC20 in VSMCs
      and this effect may be non-genomic. The RhoA/ROCK, ERK and p38 pathways were
      demonstrated to be important for the rapid effect of Dex-induced promotion of NE
      mediated contraction in VSMCs. The present results indicate that Dex may rapidly
      reverse the hyporeactivity of vasoconstriction to NE in vitro and this effect may
      be mediated by specific non-genomic mechanisms through increased activation of
      the RhoA/ROCK, ERK and p38 signaling pathways.

PMID- 23174824
TI  - Identifying stress.

PMID- 23174825
TI  - Action and coping plans related to the behavior of adherence to drug therapy
      among coronary heart disease outpatients.
AB  - OBJECTIVE: to analyze the action and coping plans related to the behavior of
      adhering to drug therapy, developed by coronary heart disease (CHD) outpatients,
      and to identify the barriers perceived to adopting this behavior. METHODS: the
      participants (n=59) were invited to formulate action plans and coping plans for
      the behavior of adhering to the cardio-protective medications and the symptom
      relief medications. RESULTS: specific action plans for taking the medications
      associated with temporal markers and the sleep-wake cycle were shown. The most
      frequently reported obstacles were forgetfulness and absence of routine in daily
      living activities. The coping plans for overcoming forgetfulness were the most
      specific. CONCLUSION: this study's findings support the application of
      implementation intentions aimed at optimizing adherence to drug therapy among
      patients with CHD.

PMID- 23174826
TI  - Clinical evolution of patients hospitalized due to the first episode of acute
      coronary syndrome.
AB  - AIM: to assess the clinical evolution of patients hospitalized due to the first
      episode of Acute Coronary Syndrome (ACS) according to its clinical manifestation.
      METHODS: data were collected from 234 patients, hospitalized between May 2006 and
      July 2009 due to the first episode of an ACS, by consulting their medical
      records. RESULTS: 234 patients were hospitalized, 140 (59.8%) due to Acute
      Myocardial Infarction (AMI). In the group with AMI, 19.3% presented
      complications, against 12.8% in the group with Unstable Angina (UA) (p=0.19).
      Angioplasty levels were higher among patients with AMI than with UA (p=0.02) and
      coronary artery bypass graft surgery was more frequent among UA patients
      (p=0.03). The majority (227; 97%) survived after the coronary event. Among the
      seven patients who died during the hospitalization, four had AMI (2.9%) and three
      UA (3.2%). CONCLUSIONS: A larger number of complications were found among
      infarction victims and the accomplishment of coronary artery bypass graft surgery
      differed between the groups.

PMID- 23174827
TI  - Quality of life in people with chronic hemodialysis: association with
      sociodemographic, medical-clinical and laboratory variables.
AB  - AIM: determine the quality of life for people in chronic hemodialysis and its
      association with sociodemographic, medical-clinical and laboratory variables.
      METHOD: exploratory, descriptive, cross-sectional study with stratified
      probability sampling. Quality of life was assessed using the KDQOL-36TM. Data
      were analyzed using SPSS statistical software. RESULTS: 354 people in chronic
      hemodialysis had low scores on most dimensions of quality of life, mainly Burden
      of Disease, Physical and Mental Component. Age, sex, education, income, time on
      dialysis, etiology of the disease, smoking, hospitalizations, albumin, creatinine
      and transplants were related. The results reveal multiple factors related to
      quality of life. CONCLUSION: there is a need to research on other aspects that
      permit focusing and optimizing the nursing care for these people.

PMID- 23174828
TI  - Body changes: antiretroviral therapy and lipodystrophy syndrome in people living
      with HIV/AIDS.
AB  - OBJECTIVE: to identify the different types of morphological alterations from
      lipodystrophy syndrome (LS) in outpatients and relate them to the therapeutic
      regimen used. METHOD: a cross-sectional study which recruited 60 patients with
      HIV and LS and 79 without LS, who consented to interview and data collection from
      their medical notes. RESULTS: the region most affected by lipoatrophy was the
      face; by lipohypertrophy, the abdomen, and by the mixed form, the alterations to
      the abdomen, face, and upper and lower limbs. CONCLUSION: among the therapeutic
      regimens, that comprised of zidovudine, lamivudine and efavirenz seemed to
      protect against LS. Nursing can act in the early identification of the changes,
      as well as providing guidance and support for patients affected by the changes in
      their body image.

PMID- 23174829
TI  - Mapping nursing goals of an intensive care unit to the Nursing Outcomes
      Classification.
AB  - AIM: to analyze whether nursing goals formulated for nursing diagnoses can be
      mapped to nursing outcomes classification and to identify the scales most
      appropriate to the outcomes mapped. METHOD: a descriptive study was developed in
      an intensive care unit. Data collection involved extraction of goals in 44
      medical records, content standardization, cross-mapping to the outcomes,
      identification of appropriated scales and validation. Descriptive analysis and
      agreement with the cross-mapping process were performed. RESULTS: nursing goals
      (59) were mapped to (28) different outcomes, with agreement of 83% in the mapping
      process. All goals were mapped to outcomes, which allows to affirm that these
      outcomes contemplates the goals elaborated to patient care. CONCLUSION: these
      results favor the inclusion of outcomes and scales validated in the planning and
      evaluation phases of the nursing process of a software in construction.

PMID- 23174830
TI  - Nursing diagnoses related to skin: operational definitions.
AB  - OBJECTIVE: to validate the operational definitions of the defining
      characteristics and risk factors of the three NANDA International (NANDA-I)
      nursing diagnoses and to revise these diagnoses' definitions. METHOD: content
      validation of nursing diagnosis. 146 defining characteristics and risk factors
      were identified in the literature in Brazilian and international databases. This
      was followed by content validation of the definitions of these diagnoses
      (presented by NANDA-I) and of the operational definitions (developed by the
      researchers) of the defining characteristics and risk factors, carried out by six
      expert nurses, regarding relevance, clarity and comprehensiveness. RESULT: of the
      146 defining characteristics and risk factors, 22 were considered redundant and
      were excluded. The experts proposed changing the definitions of the diagnoses of
      Impaired Tissue Integrity and Risk for Impaired Skin Integrity. It was possible
      to identify various defining characteristics and risk factors which are not
      present in the NANDA-I taxonomy but which are indicated in the literature.
      CONCLUSION: the process attained its objective of producing valid operational
      definitions for defining characteristics and risk factors, which will permit the
      undertaking of validation studies for these diagnoses. The study's contribution
      to advancing scientific knowledge consists in its presenting clearer operational
      definitions for these diagnoses and a higher number of defining characteristics
      and risk factors, which will assist the nurses in the identification and use of
      the same with greater accuracy in clinical practice.

PMID- 23174831
TI  - The nursing care system from a Luhmannian perspective.
AB  - OBJECTIVE: to investigate the socially-relevant communication of the nursing
      system from the Luhmannian perspective. METHOD: the investigation process was
      based in grounded theory. The data was collected between February and September
      2011, through interviews carried out with nurses and student nurses at a
      university in the South of Brazil. RESULTS: The central phenomenon--recognizing
      nursing care as an all-embracing interactive and associative phenomenon--resulted
      from the inter-weaving of three categories: learning the context of care as a
      whole, organizing the environment for the other professionals, and visibilizing
      interactive and associative care. CONCLUSION: investing in a socially relevant
      communication for nursing entails developing a code for functional
      differentiation, which may strengthen health promotion and healthy living for
      individuals, families and communities.

PMID- 23174832
TI  - Costs of most frequent nursing activities in highly dependent hospitalized
      patients.
AB  - This quantitative study aimed to identify the costs of the most frequent nursing
      activities in highly dependent hospitalized patients at a medical clinic. The non
      probabilistic convenience sample corresponded to 607 observations regarding oral
      feeding activities (OF), blood pressure verification (BP) / heart rate (HR), body
      temperature checking (BTC), performance of intimate hygiene and management of
      feeding probe. The costs identified corresponded to R$2.40 (SD+/-2.64) for OF
      feeding; R$1.26 (SD+/-0.48) to verify the BP/HR; R$1.17 (SD+/-0.46) for BTC;
      R$15.59 (SD+/-8.62) to perform intimate hygiene and R$5.95 (SD+/-2.13) for
      management of feeding probe. This study will facilitate cost management, with a
      view to avoiding waste related to unnecessary resource consumption and establish
      a correlation between costs and care delivery results.

PMID- 23174833
TI  - Nurses and care delivery to elderly women: a social phenomenological approach.
AB  - OBJECTIVE: To understand how nurses see care delivery to elderly women. METHODS:
      In this phenomenological study, ten nurses working at Primary Health Care Units
      were interviewed between September 2010 and January 2011. RESULTS: In care
      delivery, nurses consider the elderly women's knowledge background and
      biographical situation, and also value the family's participation as a care
      mediator. These professionals have the acuity to capture these women's specific
      demands, but face difficulties to deliver care to these clients. Nurses expect to
      deliver qualified care to these women. CONCLUSION: The theoretical and
      methodological approach of social phenomenology permitted revealing that the
      nurse designs qualified care to elderly women, considering the possibilities in
      the context. This includes the participation of different social actors and
      health sectors, assuming collective efforts in action strategies and professional
      training, in line with the particularities and care needs of elderly women nurses
      identify.

PMID- 23174834
TI  - Effects of a psychoeducational program for chronic pain management.
AB  - AIMS: to evaluate the impact of an eight-week psychoeducational program focused
      on pain intensity, disability and depressive symptoms of patients with chronic
      pain. METHOD: 79 patients with chronic pain of different etiologies composed the
      sample. Patients were assessed before, at the end of the intervention and six
      months after the intervention. The program was developed by a nurse using
      cognitive-behavioral strategies and was conducted by a multidisciplinary team.
      The Wilcoxon test was used to compare repeated measures. RESULTS: the
      participants' mean age was 53 years old, most were female (91%), with an average
      of 9.5 years of schooling and an average pain duration of 9.9 years. Significant
      reduction in pain intensity (p<0.001), disability (p<0.001) and depressive
      symptoms (p<0.001) was found at the end of the program. CONCLUSIONS: the
      psychoeducational program was effective in reducing pain intensity, reducing
      disability and in controlling depressive symptoms in this sample.

PMID- 23174835
TI  - Use of the nursing process at public and private centers in a health area.
AB  - AIM: to analyze whether the nursing process method is used at public and private
      centers in the health area Gipuzkoa (Basque Country) and, if yes, to analyze in
      the framework of which model and how it is used. METHOD: cross-sectional study,
      based on the analysis of the nursing records used at the 158 centers studied.
      RESULTS: the nursing process is applied at 98% of the centers. It is applied at
      all public and 18 out of 21 private centers. Virginia Henderson's model is the
      most used to apply it, and most centers use nursing diagnoses, the NIC-NOC
      terminology and standardized care plans. CONCLUSION: the use of the nursing
      process is widespread in Gipuzkoa, with greater use at public than at private
      centers.

PMID- 23174836
TI  - Nursing care practices at an outpatient care center from an integrative
      perspective.
AB  - AIM: to analyze nursing care practices at a Specialized Outpatient Care Center
      from the perspective of an integrative health care activity. METHOD: Interviews
      with 24 nursing professionals were undertaken. For data analysis, Thematic
      Content Analysis as proposed by Bardin was applied, resulting in the following
      themes: the team size and its commitment to health care; professional practices
      and activity of the nursing team. RESULTS: The size of the nursing team was
      considered insufficient, which compromises the quality of care and results in
      work overload and dissatisfaction of the nursing professionals. On the other
      hand, they were satisfied with the tasks performed day-to-day and related
      integrality to individual care, considered it essential and usually practiced it
      daily. CONCLUSION: It is considered that the nursing team has the potential and
      commitment to develop their care practice combined with the integrative
      perspective, and therefore providing quality health care to the population.

PMID- 23174837
TI  - Sleep complaints among Brazilian senior citizens from municipalities with
      different human development indices.
AB  - PURPOSE: To compare the occurrence of sleep complaints among senior citizens
      resident in the local communities of two municipalities with differing Human
      Development Indices (HDIs): Campinas, State of Sao Paulo (IDH = 0.852) and
      Parnaiba, State of Piaui (IDH = 0.674). METHOD: Descriptive study as part of the
      multicentric project going by the name of Frailty among Brazilian Senior Citizens
      (Fragilidade em Idosos Brasileiros--FIBRA). A total of 988 senior citizens were
      analysed, making use of a social and demographic questionnaire about sleep
      problems (Nottingham Health Profile); questions about naps (Minnesota Leisure
      Activity Questionnaire). The Chi-Square and Mann-Whitney tests were used in the
      analysis of the data, at a significance level of 5% (p<0.05). RESULTS: The
      chronologically advantaged individuals in Parnaiba showed a higher incidence of
      sleep complaints when compared to the senior citizens of Campinas. There was a
      significant association between municipality and the following variables: number
      of sleep complaints, non-restoring sleep, precocious awakening, difficulty in
      falling and staying asleep. CONCLUSION: The nursing staff must intervene in
      favour of the promotion of health with actions that either reduce or prevent
      these sleep-related problems.

PMID- 23174838
TI  - Accidental falls in the elderly and their relation with functional capacity.
AB  - AIM: This study aimed to determinate the prevalence of falls in the elderly and
      its relationship with the functional capacity. METHOD: This is an epidemiological
      and cross-sectional study; a two-stage cluster sample of 240 male and female
      subjects aged over 60 years was used. Data were collected from November 2010 to
      February 2011. The following questionnaires were used: socio-demographic profile,
      assessment of falls, Functional Independence Measure, Lawton and Brody Scale.
      Significance was set at 0.05. To identify the occurrence of falls and their
      relation with functional capacity, the prevalence ratio and prevalence odds
      ratios were used, as well as multiple logistic regression. RESULTS: Average age
      was 73.5 years (+/-8.4); 25% 80 years or more, with preponderance of female
      gender; 48.8% attended school between 1-4 years. The average was 1.33 falls (+/
      0.472), with prevalence in women and elderly between 60 and 79 years old; the
      most frequently sites were the backyard and bathroom. Strong correlation between
      the level of functional independence and instrumental activities and age was
      found, but no relation between elderly victims of falls and the gender and age
      variables. CONCLUSION: Women who suffered falls related to functional
      independence were predominant, which can be prevented through elderly health
      promotion strategies, a policy that serves to offer living conditions to people
      in the aging process.

PMID- 23174839
TI  - Evaluation of the vulnerability of families assisted in primary care in Brazil.
AB  - OBJECTIVE: to characterize the profiles of families in the area covered by a
      Primary Health Center and to identify those in a vulnerable situation. METHOD:
      this is an epidemiological, observational, cross-sectional and quantitative
      study. 320 home visits were made, defined by a random sample of the areas covered
      by the Urban Center 1 in the city of Sao Sebastiao, in Brazil's Federal District.
      A structured questionnaire was used for data collection, elaborated based on the
      Family Development Index (FDI). RESULTS: there was a predominance of young
      families, women, and low levels of schooling. The FDI permitted the
      identification of families in situations of "high" and "very high" vulnerability.
      The most critical dimensions were: "access to knowledge" and "access to work".
      CONCLUSION: the study indicated the importance of greater investments in the
      areas of education, work and income, and highlighted the need for the use of a
      wider concept of vulnerability by the health services.

PMID- 23174840
TI  - Burden and modifications in life from the perspective of caregivers for patients
      after stroke.
AB  - OBJECTIVE: to analyze the impact that caring has on a member of the family caring
      for a patient after a cerebrovascular accident, correlating life modifications
      and mental suffering with the perceived burden. METHOD: a cross-sectional,
      quantitative study, undertaken in January-April 2010 in Fortaleza, Ceara, Brazil.
      RESULT: 61 individuals were investigated, monitored by three hospitals' Home Care
      Program. Data collection was through interviews for identifying life changes, and
      through the application of three scales for investigating perceived burden,
      mental state and mental suffering. Respectively these were the Caregiver Burden
      Scale (CBS), the Mini-Mental State Examination (MMSE) and the Self Reported
      Questionnaire (SRQ). The majority of the carers were female, married, and the
      children of the stroke patients. The average age was 48.2 years (+/-12.4). The
      most-cited life modifications referred to the daily routine, to leisure
      activities, and to exhaustion or tiredness. Regarding burden, the dimensions of
      General tension, Isolation and Disappointment stood out. It was ascertained that
      overload was more severe when the carer presented more symptoms of psychological
      distress, in the absence of a secondary carer, and when the principal carers
      reported perceiving changes in their bodies and health. CONCLUSION: an
      association between burden and the carer's mental state was not observed.
      Understanding the care, through analysis of the burden and of the knowledge of
      the biopsychosocial situation will provide support for the nurse's work in
      reducing the overload for family caregivers.

PMID- 23174841
TI  - The violence in everyday of prostitution of women: invisibility and ambiguities.
AB  - OBJECTIVE: To reveal the meaning of violence in everyday female prostitution.
      METHOD: we used a phenomenological approach of Martin Heidegger. The survey was
      conducted in Teresina / Piaui / Brazil, with 11 women members of the Association
      of Prostitutes of Piaui. The data were produced by means of open interviews
      conducted by a script with questions regarding their experience as a prostitute
      and its relationship to violence. RESULTS: The reports indicate that it is
      prostitution a risky activity in which gender violence is a phenomenon present.
      In the relational world, prostitution and violence are intertwined in the face of
      negotiations established between women and men with formal contracts in the dark,
      verbally, without witnesses, and whose object of contract is the woman herself
      for the purpose of providing sexual pleasure to the contractor. Through
      interpretative analysis was possible to understand the lived violence leads women
      to remain in daily life where is this fear, inauthenticity and ambiguity.
      CONCLUSIONS: violence unveils lived relations of domination and assertion of male
      power, manifested by violence physical, psychological, moral and sexual. The
      study advances in scientific knowledge by showing that violence against women, in
      prostitution, must be understood as a process factual as well as the suffering
      experienced by them.

PMID- 23174842
TI  - Burnout and labour aspects in the nursing teams at two medium-sized hospitals.
AB  - PURPOSE: The aim of this study is to identify the occurrence of Burnout Syndrome
      (BS) and assess its relationship with different labour-related aspects, among
      nursing professionals at two medium-sizes hospitals in the city of Caceres.
      METHOD: This is a transversal and descriptive study, with a sample totalling 141
      subjects. As an instrument of research, we used a questionnaire for the
      limitation of labour-related aspects, with the addition of the Maslach Burnout
      Inventory (MBI). RESULTS: Out of the 141 professional people considered, 13 had
      BS, according to the MBI. In relation to the different labour aspects, the
      professional people most affected were those with: work regime based on pay by
      the day, a working week of 30 hours, regularly hired, with double employment,
      lower graduation period, less time spent at the unit, and active in the
      administrative segment. CONCLUSIONS: Hence, there was the demonstration of the
      presence of BS within the sample, showing the need for the proposal of
      organisational changes within the working environment so as to reduce these
      factors and their interference on the health of the worker.

PMID- 23174844
TI  - Applicability of auriculotherapy in reducing stress and as a coping strategy in
      nursing professionals.
AB  - AIMS: randomized clinical trial aimed at evaluating the auriculotherapy in
      reducing stress levels in 75 nursing professionals and analyze the coping domains
      that have changed after treatment. METHODOLOGY: volunteers were divided into 3
      groups (Control, Needles and Seeds) and received eight sessions at Shenmen,
      Kidney and Brainstem points. The Control Group didn't receive any intervention.
      RESULTS: ANOVA test showed statistical differences in stress levels for
      Needle/Control Groups in the third and fourth assessments, according to Stress
      Symptoms List when compared the three groups in four assessments. For the
      Inventory of Folkman/Lazarus, a significant difference was obtained for Spacing
      domain between needle/control. In analysis within the same group, differences
      were found for Confrontation in fourth assessment between Needle/Control Groups
      and for Social Support in the third one between Seeds/Control Groups. CONCLUSION:
      The auriculotherapy decreased stress levels, changed Coping domains after
      treatment, suggesting that both Auriculotherapy with needles and seeds can
      produce positive impact to improve strategy Coping in the nursing team. However,
      more studies are needed to conceive the extent of the technique.

PMID- 23174843
TI  - Psychosocial stress and minor psychiatric disorders among agentes
      socioeducadores.
AB  - OBJECTIVE: to ascertain the association between psychosocial stress and the
      occurrence of Minor Psychiatric Disorders in agentes socioeducadores. METHOD: a
      cross-sectional study with 381 agentes socioeducadores from the Centros de
      Atendimento Socioeducativo in the Brazilian state of Rio Grande do Sul, in 2011.
      Brazilian versions of the social demand-control-support at work scale were used,
      and of the Self Reporting Questionnaire-20. RESULTS: the prevalence of minor
      psychiatric disorders was 50.1%. The chances of being classified with such a
      disorder were higher in the high strain work quadrant (OR=2.05; CI95%=1.03-4.09)
      and active work quadrant (OR=1.99; CI95%=1.09-3.63) when compared to that of low
      strain, after adjustment for potentially confusing factors. CONCLUSION: there is
      a positive association between psychosocial stress (high strain and active work)
      and minor psychiatric disorders among agentes socioeducadores. In order to
      prevent mental illness among these workers, the planning of health promotion
      actions is necessary.

PMID- 23174845
TI  - Cross-cultural adaptation and validation of the European Heart Failure Self-Care
      Behavior Scale for Brazilian Portuguese.
AB  - OBJECTIVE: To adapt and validate a Brazilian Portuguese version of the European
      Heart Failure Self-Care Behavior Scale. METHODS: The cross-cultural adaptation
      (translation, synthesis, back-translation, expert committee review, and
      pretesting) and validation (assessment of face validity, content validity, and
      internal consistency reliability) were carried out in accordance with the
      literature. The European Heart Failure Self-Care Behavior Scale assesses key
      components of self-care: recognition of the signs and symptoms of decompensated
      heart failure (HF) and decision-making when these signs and symptoms arise. It
      comprises 12 items (range 12-60, where lower scores indicate better self-care).
      RESULTS: The sample comprised 124 HF patients with a mean age of 62.3 +/- 12
      years. The Cronbach's Alpha internal consistency was 0.70 and the intraclass
      correlation coefficient for reproducibility was 0.87. CONCLUSION: Face and
      content validity, internal consistency and reproducibility have lended validity
      and reliability for the use of the instrument in Brazil.

PMID- 23174846
TI  - Endotracheal suction in intubated critically ill adult patients undergoing
      mechanical ventilation: a systematic review.
AB  - AIM: identify and analyze in the literature the evidence of randomized controlled
      trials on care related to the suctioning of endotracheal secretions in intubated,
      critically ill adult patients undergoing mechanical ventilation. METHOD: the
      search was conducted in the PubMed, EMBASE, CENTRAL, CINAHL and LILACS databases.
      From the 631 citations found, 17 studies were selected. RESULTS: Evidence was
      identified for six categories of intervention related to endotracheal suctioning,
      which were analyzed according to outcomes related to hemodynamic and blood gas
      alterations, microbial colonization, nosocomial infection, and others.
      CONCLUSIONS: although the evidence obtained is relevant to the practice of
      endotracheal aspiration, the risks of bias found in the studies selected
      compromise the evidence's reliability.

PMID- 23174847
TI  - Laugier-Hunziker syndrome: a report of three cases and literature review.
AB  - Laugier-Hunziker syndrome (LHS) is an acquired pigmentary condition affecting
      lips, oral mucosa and acral area, frequently associated with longitudinal
      melanonychia. There is neither malignant predisposition nor underlying systemic
      abnormality associated with LHS. Herein, we present three uncommon cases of LHS
      with possibly new feature of nail pigmentation, which were diagnosed during the
      past 2 years. We also review the clinical and histological findings, differential
      diagnosis, and treatment of the syndrome in published literature.

PMID- 23174849
TI  - Effects of surface modification on photocatalytic activity of CdS nanocrystals
      studied by photoluminescence spectroscopy.
AB  - The surface features of semiconductors play very important roles in
      photocatalytic processes but they are far from being well understood. In this
      work, we used CdS nanocrystals (NCs) as a model semiconductor photocatalyst to
      investigate the influence of surface features on photocatalytic activity. The
      effects of surface modification on the recombination behavior were studied by
      photoluminescence (PL) spectroscopy. The surface of CdS NCs was modified by
      tuning the surface S/Cd ratio or by co-loading with Pt and/or PdS co-catalysts.
      It was found that the surface modifications significantly affect the emission
      bands at ~540 nm due to shallow traps and ~650 nm assigned to S(2-) vacancies,
      and consequently the photocatalytic activities. Without co-catalysts loading, the
      excited carriers are readily transferred to the shallow traps, while they are
      readily transferred to the co-catalysts upon co-catalysts loading. These results
      demonstrate that the surface features are crucial to photocatalytic activity of
      the CdS NCs. The surface modification is helpful for the excited carriers to
      transfer to either the shallow trap states or co-catalysts, resulting in higher
      quantum efficiency of photocatalytic H(2) production.

PMID- 23174850
TI  - Two-step self-assembly of iron oxide into three-dimensional hollow magnetic
      porous microspheres and their toxic ion adsorption mechanism.
AB  - Hollow magnetic porous Fe(3)O(4)/alpha-FeOOH microspheres, with abundant surface
      hydroxyl groups and carbonate-like species, were prepared using a simple template
      free solution method. The obtained magnetic microspheres were characterized by
      field emission scanning electron microscopy, transmission electron microscopy,
      nitrogen adsorption-desorption isotherms, vibrating sample magnetometry and X-ray
      diffraction. A two-step self-assembly mechanism for the microspheres was proposed
      based on the morphology of the products produced with different reaction times
      and the X-ray diffraction of the raw product grown at the initial stage. The
      toxic ion adsorption properties of the microspheres were investigated for As(V),
      Cr(VI), Cd(II) and Hg(II) ion removal. The adsorption mechanism was studied by an
      X-ray photoelectron spectrometer and Fourier transform infrared absorption
      spectroscopy . The results suggest that both the surface hydroxyl groups and the
      carbonate-like species participated in the ion-exchange process.

PMID- 23174848
TI  - Experimental approaches for gene regulatory network construction: the chick as a
      model system.
AB  - Setting up the body plan during embryonic development requires the coordinated
      action of many signals and transcriptional regulators in a precise temporal
      sequence and spatial pattern. The last decades have seen an explosion of
      information describing the molecular control of many developmental processes. The
      next challenge is to integrate this information into logic "wiring diagrams" that
      visualize gene actions and outputs, have predictive power and point to key
      control nodes. Here, we provide an experimental workflow on how to construct gene
      regulatory networks using the chick as model system.

PMID- 23174851
TI  - Phonons and colossal thermal expansion behavior of Ag3Co(CN)6 and Ag3Fe(CN)6.
AB  - Recently colossal volume thermal expansion has been observed in the framework
      compounds Ag(3)Co(CN)(6) and Ag(3)Fe(CN)(6). We have measured phonon spectra
      using neutron time-of-flight spectroscopy as a function of temperature and
      pressure. Ab initio calculations were carried out for the sake of analysis and
      interpretation. Bonding is found to be very similar in the two compounds. At
      ambient pressure, modes in the intermediate frequency part of the vibrational
      spectra in the Co compound are shifted slightly to higher energies as compared to
      the Fe compound. The temperature dependence of the phonon spectra gives evidence
      for a large explicit anharmonic contribution to the total anharmonicity for low
      energy modes below 5 meV. We have found that modes are mainly affected by the
      change in size of the unit cell, which in turn changes the bond lengths and
      vibrational frequencies. Thermal expansion has been calculated via the volume
      dependence of phonon spectra. Our analysis indicates that Ag phonon modes within
      the energy range 2-5 meV are strongly anharmonic and major contributors to
      thermal expansion in both systems. The application of pressure hardens the low
      energy part of the phonon spectra involving Ag vibrations and confirms the highly
      anharmonic nature of these modes.

PMID- 23174852
TI  - Gold nanocluster-based electrochemically controlled fluorescence switch surface
      with prussian blue as the electrical signal receptor.
AB  - A highly robust electrochemically controlled fluorescence switch based on
      ultrasmall Au nanoclusters has been designed by the aid of the electrochemical
      redox reaction of prussian blue.

PMID- 23174853
TI  - Competition between surfactant micellization and complexation by cyclodextrin.
AB  - Supramolecular property systems composed of alkyltrimethylammonium surfactants
      and beta-cyclodextrin were studied by means of a chemical probe. Solvolysis of 4
      methoxybenzenesulfonyl chloride (MBSC) was used in the mixed systems with the aim
      of being able to determine the concentration of uncomplexed cyclodextrin in
      equilibrium with the micellar system. The surfactants used enabled us to vary the
      length of the hydrocarbon chain between 6 and 18 carbon atoms. In all cases the
      existence of a significant concentration of uncomplexed CD was observable in
      equilibrium with the micellar system. The percentage of uncomplexed cyclodextrin
      increases both on increasing and decreasing the surfactant alkyl chain length,
      being minimal for alkyl chains between 10-12 carbon atoms. This behavior is a
      consequence of two simultaneous processes: complexation of surfactant monomers by
      the cyclodextrin and surfactant self-assembly to form micellar aggregates. By
      using Gibbs free energies for micellization and surfactant complexation by beta
      CD, we can quantitatively explain the observed behavior.

PMID- 23174854
TI  - Low concentration of arsenic-induced aberrant mitosis in keratinocytes through
      E2F1 transcriptionally regulated Aurora-A.
AB  - Chronic exposure to low-concentration arsenic promotes cell proliferation and
      carcinogenesis both in vitro and in vivo. Centrosome amplification, the major
      cause of chromosome instability, occurs frequently in cancers. Aurora-A is a
      mitotic kinase and causes centrosome amplification and chromosome instability
      when overexpressed. Our previous study revealed that low-concentration arsenic
      induces Aurora-A overexpression in immortalized bladder cells. In this study, we
      hypothesized that low-concentration arsenic induces aberrant mitosis in
      keratinocytes due to Aurora-A overexpression. The specimen of Bowen's disease
      (BD) and squamous cell carcinoma obtained from arseniasis-endemic areas in Taiwan
      showed Aurora-A overexpression. The mRNA/protein levels and kinase activity of
      Aurora-A were increased in immortalized keratinocyte HaCaT cells after arsenic
      treatment at low concentration (< 1uM). Aberrant spindles, multiple centrosomes,
      and multinucleated cells were detected under fluorescent microscopy in HaCaT
      cells after arsenic treatment. These findings were associated with increased
      expression of Aurora-A. We further revealed that Aurora-A was regulated by
      arsenic-induced transcriptional factor E2F1 as demonstrated by chromosome
      immunoprecipitation, promoter activity, and small interfering RNA assays.
      Finally, in arsenic-treated HaCaT cells and in BD, a significant increase of
      dysfunctional p53 was found, and this event correlated with the increase in
      expression of Aurora-A. Altogether, our data suggest that low concentration of
      arsenic induces activation of E2F1-Aurora-A axis and results in aberrant mitosis
      of keratinocytes. Overexpression of Aurora-A and dysfunctional p53 may act
      synergistically to trigger skin tumor formation. Our findings suggest that Aurora
      A may be a potential target for the prevention and treatment of arsenic-related
      cancers.

PMID- 23174855
TI  - Impact of diabetes mellitus on bladder uroepithelial cells.
AB  - Diabetic bladder dysfunction (DBD), a prevalent complication of diabetes mellitus
      (DM), is characterized by a broad spectrum of symptoms including urinary urgency,
      frequency, and incontinence. As DBD is commonly diagnosed late, it is important
      to understand the chronic impact of DM on bladder tissues. While changes in
      bladder smooth muscle and innervation have been reported in diabetic patients,
      the impact of DM on the specialized epithelial lining of the urinary bladder, the
      urothelium (UT), is largely unknown. Quantitative polymerase chain reaction
      analysis and electron microscopy were used to evaluate UT gene expression and
      cell morphology 3, 9, and 20 wk following streptozotocin (STZ) induction of DM in
      female Sprague-Dawley rats compared with age-matched control tissue. Desquamation
      of superficial (umbrella) cells was noted at 9 wk DM, indicating a possible
      breach in barrier function. One causative factor may be metabolic burden due to
      chronic hyperglycemia, suggested by upregulation of the polyol pathway and
      glucose transport genes in DM UT. While superficial UT repopulation occurred by
      20 wk DM, the phenotype was different, with significant upregulation of receptors
      associated with UT mechanosensation (transient receptor potential vanilloid
      subfamily member 1; TRPV1) and UT autocrine/paracrine signaling (acetylcholine
      receptors AChR-M2 and -M3, purinergic receptors P2X(2) and P2X(3)). Compromised
      barrier function and alterations in UT mechanosensitivity and cell signaling
      could contribute to bladder instability, hyperactivity, and altered bladder
      sensation by modulating activity of afferent nerve endings, which appose the
      urothelium. Our results show that DM impacts urothelial homeostasis and may
      contribute to the underlying mechanisms of DBD.

PMID- 23174856
TI  - Effects of short-term dietary nitrate supplementation on blood pressure, O2
      uptake kinetics, and muscle and cognitive function in older adults.
AB  - Dietary nitrate (NO(3)(-)) supplementation has been shown to reduce resting blood
      pressure and alter the physiological response to exercise in young adults. We
      investigated whether these effects might also be evident in older adults. In a
      double-blind, randomized, crossover study, 12 healthy, older (60-70 yr) adults
      supplemented their diet for 3 days with either nitrate-rich concentrated beetroot
      juice (BR; 2 * 70 ml/day, ~9.6 mmol/day NO(3)(-)) or a nitrate-depleted beetroot
      juice placebo (PL; 2 * 70 ml/day, ~0.01 mmol/day NO(3)(-)). Before and after the
      intervention periods, resting blood pressure and plasma [nitrite] were measured,
      and subjects completed a battery of physiological and cognitive tests. Nitrate
      supplementation significantly increased plasma [nitrite] and reduced resting
      systolic (BR: 115 +/- 9 vs. PL: 120 +/- 6 mmHg; P < 0.05) and diastolic (BR: 70
      +/- 5 vs. PL: 73 +/- 5 mmHg; P < 0.05) blood pressure. Nitrate supplementation
      resulted in a speeding of the Vo(2) mean response time (BR: 25 +/- 7 vs. PL: 28
      +/- 7 s; P < 0.05) in the transition from standing rest to treadmill walking,
      although in contrast to our hypothesis, the O(2) cost of exercise remained
      unchanged. Functional capacity (6-min walk test), the muscle metabolic response
      to low-intensity exercise, brain metabolite concentrations, and cognitive
      function were also not altered. Dietary nitrate supplementation reduced resting
      blood pressure and improved Vo(2) kinetics during treadmill walking in healthy
      older adults but did not improve walking or cognitive performance. These results
      may have implications for the enhancement of cardiovascular health in older age.

PMID- 23174857
TI  - SK channel-selective opening by SKA-31 induces hyperpolarization and decreases
      contractility in human urinary bladder smooth muscle.
AB  - Overactive bladder (OAB) is often associated with increased involuntary detrusor
      smooth muscle (DSM) contractions during the bladder-filling phase. To develop
      novel therapies for OAB, it is critical to better understand the mechanisms that
      control DSM excitability and contractility. Recent studies showed that small
      conductance Ca(2+)-activated K(+) (SK) channels, SK3 channels, in particular,
      regulate human DSM function. However, the concept that SK channel-selective
      pharmacological activation can decrease the excitability and contractility
      directly in human DSM needs further exploration. Here, we studied the effect of
      the novel and potent SK channel activator, SKA-31 (or naphtho [1,2-d]thiazol-2
      ylamine), on human DSM excitability and contractility at the cellular and tissue
      level. We used isometric tension recordings on human DSM-isolated strips and the
      perforated patch-clamp technique on freshly isolated native human DSM cells. SKA
      31 significantly decreased spontaneous phasic contractions of DSM-isolated
      strips. In the presence of the SK channel blocker, apamin, the inhibitory effects
      of SKA-31 on the DSM spontaneous phasic contractions were significantly reduced.
      SKA-31 decreased the carbachol- and KCl-induced contractions in human DSM strips.
      Electrical field stimulation-induced contractions were significantly attenuated
      in the presence of SKA-31 at all stimulation frequencies (0.5-50 Hz). SKA-31
      hyperpolarized the resting membrane potential of human DSM cells. Apamin
      abolished the hyperpolarizing effect of SKA-31, indicating the involvement of SK
      channel activation. These results support the concept that pharmacological
      activation of SK channels with selective openers may represent an attractive new
      pharmacological approach for decreasing DSM excitability and contractility, thus
      controlling OAB.

PMID- 23174858
TI  - Decrease in the red cell cofactor 2,3-diphosphoglycerate increases hemoglobin
      oxygen affinity in the hibernating brown bear Ursus arctos.
AB  - During winter hibernation, brown bears (Ursus arctos) reduce basal O(2)
      consumption rate to ~25% compared with the active state, while body temperature
      decreases moderately (to ~30 degrees C), suggesting a temperature-independent
      component in their metabolic depression. To establish whether changes in O(2)
      consumption during hibernation correlate with changes in blood O(2) affinity, we
      took blood samples from the same six individuals of hibernating and
      nonhibernating free-ranging brown bears during winter and summer, respectively. A
      single hemoglobin (Hb) component was detected in all samples, indicating no
      switch in Hb synthesis. O(2) binding curves measured on red blood cell lysates at
      30 degrees C and 37 degrees C showed a less temperature-sensitive O(2) affinity
      than in other vertebrates. Furthermore, hemolysates from hibernating bears
      consistently showed lower cooperativity and higher O(2) affinity than their
      summer counterparts, regardless of the temperature. We found that this increase
      in O(2) affinity was associated with a significant decrease in the red cell Hb
      cofactor 2,3-diphosphoglycerate (DPG) during hibernation to approximately half of
      the summer value. Experiments performed on purified Hb, to which DPG had been
      added to match summer and winter levels, confirmed that the low DPG content was
      the cause of the left shift in the Hb-O(2) equilibrium curve during hibernation.
      Levels of plasma lactate indicated that glycolysis is not upregulated during
      hibernation and that metabolism is essentially aerobic. Calculations show that
      the increase in Hb-O(2) affinity and decrease in cooperativity resulting from
      decreased red cell DPG may be crucial in maintaining a fairly constant tissue
      oxygen tension during hibernation in vivo.

PMID- 23174860
TI  - Initial orthostatic hypotension and cerebral blood flow regulation: effect of
      alpha1-adrenoreceptor activity.
AB  - We examined the hypothesis that alpha(1)-adrenergic blockade would lead to an
      inability to correct initial orthostatic hypotension (IOH) and cerebral
      hypoperfusion, leading to symptoms of presyncope. Twelve normotensive humans
      (aged 25 +/- 1 yr; means +/- SE) attempted to complete a 3-min upright stand, 90
      min after the administration of either alpha(1)-blockade (prazosin, 1 mg/20 kg
      body wt) or placebo. Continuous beat-to-beat measurements of middle cerebral
      artery velocity (MCAv; Doppler), blood pressure (finometer), heart rate, and end
      tidal Pco(2) were obtained. Compared with placebo, the alpha(1)-blockade reduced
      resting mean arterial blood pressure (MAP) (-15%; P < 0.01); MCAv remained
      unaltered (P >= 0.28). Upon standing, although the absolute level of MAP was
      lower following alpha(1)-blockade (39 +/- 10 mmHg vs. 51 +/- 14 mmHg), the
      relative difference in IOH was negligible in both trials (mean difference in MAP:
      2 +/- 2 mmHg; P = 0.50). Compared with the placebo trial, the declines in MCAv
      and Pet(CO(2)) during IOH were greater in the alpha(1)-blockade trial by 12 +/- 4
      cm/s and 4.4 +/- 1.3 mmHg, respectively (P <= 0.01). Standing tolerance was
      markedly reduced in the alpha(1)-blockade trial (75 +/- 17 s vs. 180 +/- 0 s; P <
      0.001). In summary, while IOH was little affected by alpha(1)-blockade, the
      associated decline in MCAv was greater in the blockade condition. Unlike in the
      placebo trial, the extent of IOH and cerebral hypoperfusion failed to recover
      toward baseline in the alpha(1)-blockade trial leading to presyncope. Although
      the development of IOH is not influenced by the alpha(1)-adrenergic receptor
      pathway, this pathway is critical in the recovery from IOH to prevent cerebral
      hypoperfusion and ultimately syncope.

PMID- 23174861
TI  - Nighttime snacking reduces whole body fat oxidation and increases LDL cholesterol
      in healthy young women.
AB  - The increase in obesity and lipid disorders in industrialized countries may be
      due to irregular eating patterns. Few studies have investigated the effects of
      nighttime snacking on energy metabolism. We examined the effects of nighttime
      snacking for 13 days on energy metabolism. Eleven healthy women (means +/- SD;
      age: 23 +/- 1 yr; body mass index: 20.6 +/- 2.6 kg/m(2)) participated in this
      randomized crossover trial for a 13-day intervention period. Subjects consumed a
      specified snack (192.4 +/- 18.3 kcal) either during the daytime (10:00) or the
      night time (23:00) for 13 days. On day 14, energy metabolism was measured in a
      respiratory chamber without snack consumption. An oral glucose tolerance test was
      performed on day 15. Relative to daytime snacking, nighttime snacking
      significantly decreased fat oxidation (daytime snacking: 52.0 +/- 13.6 g/day;
      nighttime snacking: 45.8 +/- 14.0 g/day; P = 0.02) and tended to increase the
      respiratory quotient (daytime snacking: 0.878 +/- 0.022; nighttime snacking:
      0.888 +/- 0.021; P = 0.09). The frequency of snack intake and energy intake, body
      weight, and energy expenditure were not affected. Total and low-density
      lipoprotein (LDL) cholesterol significantly increased after nighttime snacking
      (152 +/- 26 mg/dl and 161 +/- 29 mg/dl; P = 0.03 and 76 +/- 20 mg/dl and 83 +/-
      24 mg/dl; P = 0.01, respectively), but glucose and insulin levels after the
      glucose load were not affected. Nighttime snacking increased total and LDL
      cholesterol and reduced fat oxidation, suggesting that eating at night changes
      fat metabolism and increases the risk of obesity.

PMID- 23174859
TI  - Early life stress induces renal dysfunction in adult male rats but not female
      rats.
AB  - Maternal separation (MatSep) is a model of behavioral stress during early life.
      We reported that MatSep exacerbates ANG II-induced hypertension in adult male
      rats. The aims of this study were to determine whether exposure to MatSep in
      female rats sensitizes blood pressure to ANG II infusion similar to male MatSep
      rats and to elucidate renal mechanisms involved in the response in MatSep rats.
      Wistar Kyoto (WKY) pups were exposed to MatSep 3 h/day from days 2 to 14, while
      control rats remained with their mothers. ANG II-induced mean arterial pressure
      (MAP; telemetry) was enhanced in female MatSep rats compared with control female
      rats but delayed compared with male MatSep rats. Creatinine clearance (Ccr) was
      reduced in male MatSep rats compared with control rats at baseline and after ANG
      II infusion. ANG II infusion significantly increased T cells in the renal cortex
      and greater histological damage in the interstitial arteries of male MatSep rats
      compared with control male rats. Plasma testosterone was greater and estradiol
      was lower in male MatSep rats compared with control rats with ANG II infusion.
      ANG II infusion failed to increase blood pressure in orchidectomized male MatSep
      and control rats. Female MatSep and control rats had similar Ccr, histological
      renal analysis, and sex hormones at baseline and after ANG II infusion. These
      data indicate that during ANG II-induced hypertension, MatSep sensitizes the
      renal phenotype in male but not female rats.

PMID- 23174862
TI  - A small-molecule RGD-integrin antagonist inhibits cell adhesion, cell migration
      and induces anoikis in glioblastoma cells.
AB  - In cancer cells integrins modulate important cellular events that regulate the
      metastasic cascade which involves detachment from the tumor mass, dissemination
      and attachment to the oncogenic niche. The alpha5beta1, alphavbeta3 and
      alphavbeta5 integrins are widely expressed in different cancer types and
      recognize the tripeptide Arg-Gly-Asp (RGD) motif present in several extracellular
      matrix proteins. In human glioblastoma, alphavbeta3 integrin expression
      correlates with tumor grade, suggesting that this integrin may play a crucial
      role in the highly infiltrative behavior of high grade gliomas. However, few
      selective RGD-like antagonists have been developed and few studies have
      investigated their effects in in vitro models of human glioblastoma. In this
      study, we investigated several cellular effects and the underlying molecular
      mechanisms exerted by a new small-molecule RGD antagonist, 1a-RGD, in the U251
      and U373 human glioblastoma cell lines. Treatment with 1a-RGD (20 uM)
      demonstrated a weak effect on cell viability and cell proliferation but strongly
      inhibited cell attachment and cell migration together with actin cytoskeleton
      disassembly. Prolonged 1a-RGD treatment (72 h) induced anoikis, assessed by
      Annexin staining and nucleosome assay, particularly in the detached cells. When
      integrin-linked transduction pathways were investigated, 1aRGD was found to exert
      a marked reduction in focal adhesion kinase (FAK) phosphorylation without
      affecting the AKT- and ERK-dependent pathways. Our data indicate that 1a-RGD,
      probably via modulation of the FAK-dependent pathway, inhibits cell migration and
      attachment and induces anoikis in glioblastoma cells. This novel finding suggests
      that the development of an RGD-like molecule may represent a promising tool for
      the pharmacological approach aimed at reducing the malignancy of glioblastoma
      cells.

PMID- 23174863
TI  - Treadmill exercise during pregnancy ameliorates post-traumatic stress disorder
      induced anxiety-like responses in maternal rats.
AB  - Post-traumatic stress disorder (PTSD) is an anxiety disorder triggered by life
      threatening events that cause intense fear. Exercise is known to have protective
      effects on neuropsychiatric diseases. The present study investigated whether
      treadmill exercise during pregnancy reduced or alleviated symptoms of PTSD in
      maternal rats. To induce predator stress in pregnant rats, rats were exposed to a
      hunting dog in an enclosed room. Exposure time was three 10-min daily sessions
      separated by 1 h, starting at week 1 of pregnancy until delivery. Pregnant rats
      in the exercise group were forced to run on a treadmill for 30 min once a day,
      starting one week following pregnancy until delivery. Rats receiving predator
      stress during pregnancy exhibited PTSD anxiety-like behaviors following delivery.
      Expression of 5-hydroxytryptamine (5-HT) and its synthesizing enzyme tryptophan
      hydroxylase (TPH) in the dorsal raphe was increased compared with unstressed
      rats. Expression of c-Fos and neuronal nitric oxide synthases (nNOS) in the
      hypothalamus and locus coeruleus were higher in the rats receiving stress during
      pregnancy compared with unstressed rats. By contrast, treadmill exercise during
      pregnancy ameliorated anxiety-like behaviors and reduced the expression of 5-HT,
      TPH, c-Fos and nNOS in the PTSD maternal rats. The results of the present study
      indicate that exercise during pregnancy is suitable for use as a therapeutic
      strategy to reduce anxiety-related disorders, including PTSD.

PMID- 23174864
TI  - Telemedicine: a technological revolution.

PMID- 23174865
TI  - Remarks about systematic reviews of diagnostic tests.

PMID- 23174866
TI  - Burnout syndrome and weekly workload of on-call physicians: cross-sectional
      study.
AB  - CONTEXT AND OBJECTIVES: Burnout syndrome (BS) is characterized by three
      dimensions: emotional exhaustion, depersonalization and reduced personal
      fulfillment. The objectives of this study were to evaluate a possible association
      between BS and weekly workload, and to describe the prevalence of BS and the
      sociodemographic and occupational profile of on-call physicians in Maceio. DESIGN
      AND SETTING: Cross-sectional study in intensive care units (ICU) at public and
      private hospitals in Maceio. METHODS: A self-administered form was used to
      evaluate sociodemographic characteristics and BS through the Maslach Burnout
      Inventory (MBI) among 67 on-call physicians at ICUs in Maceio. Pearson's R
      correlation test was used to compare workload and emotional exhaustion. For other
      dimensions, Spearman's S test was used (P < 0.05). Other variables were
      represented by simple frequencies. The 95% confidence interval was calculated for
      each variable. RESULTS: Among the physicians studied, 55.22% were female and the
      mean age was 43.9 +/- 8.95 years. The mean weekly workload on call was 43.85 +/-
      24.49 hours. The frequency of high scores in at least one of the three dimensions
      of MBI was 70.14%. CONCLUSIONS: Despite the high prevalence of BS, especially
      among physicians who did not practice regular physical activity, our data did not
      indicate any significant correlation between weekly workload and any of the three
      dimensions of BS in this sample. The high prevalence of BS draws attention to the
      importance of investigating other possible causes, in order to prevent and
      adequately treat it.

PMID- 23174867
TI  - Assessing glomerular filtration rate in patients with severe heart failure:
      comparison between creatinine-based formulas.
AB  - CONTEXT AND OBJECTIVE: Severe heart failure is highly associated with chronic
      kidney disease (CKD). Serum creatinine is a poor indicator of renal function and
      glomerular filtration rate (GFR) estimation is an accessible method for assessing
      renal function. The most popular formulas for GFR estimation are the Cockcroft
      Gault (CG), the four-variable Simplified Modification of Diet in Renal Disease
      (sMDRD) and the recently introduced CKD-Epidemiology Collaboration (CKD-EPI). The
      objective of the study was to analyze the correlation between these three
      equations for estimating GFR in patients with severe heart failure. DESIGN AND
      SETTING: Cross-sectional observational study at a university reference center.
      METHODS: GFR was estimated in patients with severe heart failure who were
      awaiting heart transplantation, using the CG, sMDRD and CKD-EPI formulas. These
      estimates were analyzed using Pearson's correlation and Bland-Altman analysis.
      RESULTS: This study included 157 patients, of whom 32 (20.3%) were female. Normal
      serum creatinine concentration was observed in 21.6%. The mean GFR according to
      CG, sMDRD and CKD-EPI was 70.1 +/- 29.5, 70.7 +/- 37.5 and 73.7 +/- 30.1
      ml/min/1.73 m2; P > 0.05. Pearson's coefficient demonstrated good correlations
      between all the formulas, as did Bland-Altman. However, the patients presented
      GFR < 60 ml/min more frequently with the sMDRD formula (54.1% versus 40.2% for CG
      and 43.2% for CKD-EPI; P = 0.02). CONCLUSION: Despite the good correlation and
      agreement between the three methods, the sMDRD formula classified more patients
      as presenting GFR less than 60 ml/min.

PMID- 23174868
TI  - Autoimmune thyroid disease as a risk factor for angioedema in patients with
      chronic idiopathic urticaria: a case-control study.
AB  - CONTEXT AND OBJECTIVE: An association between chronic idiopathic urticaria (CIU)
      and autoimmune thyroid disease (ATD) has been reported. However, there have not
      been any reports on whether ATD raises the risk of angioedema, which is a more
      severe clinical presentation of CIU. Thus, the aim of the present study was to
      evaluate whether the risk of angioedema is increased in patients with CIU and
      ATD. DESIGN AND SETTING: Case-control study including 115 patients with CIU at a
      tertiary public institution. METHODS: The patients were evaluated with regard to
      occurrence of angioedema and presence of ATD, hypothyroidism or hyperthyroidism.
      RESULTS: Angioedema was detected in 70 patients (60.9%). There were 22 cases
      (19.1%) of ATD, 19 (16.5%) of hypothyroidism and nine (7.8%) of hyperthyroidism.
      The risk among patients with ATD was 16.2 times greater than among those without
      this thyroid abnormality (confidence interval, CI = 2.07-126.86). The odds ratio
      for hypothyroidism was 4.6 (CI = 1.00-21.54) and, for hyperthyroidism, 3.3 (CI =
      0.38-28.36). CONCLUSIONS: Patients with CIU and ATD presented greater risk of
      angioedema, which reinforces the idea that a relationship exists between this
      allergic condition and thyroid autoimmunity. This finding could imply that such
      patients require specifically directed therapy.

PMID- 23174869
TI  - Psychomotor development of preterm infants aged 6 to 12 months.
AB  - CONTEXT AND OBJECTIVE: The immaturity of preterm infants' organ systems may lead
      to difficulties in adapting to different environmental stimuli. The aim was to
      compare the psychomotor development of preterm infants (with corrected age) and
      term infants aged 6 to 12 months and to investigate associated factors. DESIGN
      AND SETTING: Cross-sectional analytical study conducted at Hospital das Clinicas,
      Universidade Federal de Pernambuco. METHODS: The sample consisted of 135 infants
      (45 preterm and 90 full-term) aged 6 to 12 months. Neuropsychomotor development
      was assessed using the Bayley III cognitive, language and motor subscales.
      Biological, socioeconomic and demographic data were gathered from medical records
      and through interviews with mothers. RESULTS: The mean cognitive, language and
      motor indices were within the range of normality for the sample as a whole. No
      significant difference in the development of infants born preterm and full-term
      was observed, except for expressive communication, in which preterm infants
      presented a lower index. Motor development was influenced by biological factors,
      and the poorest performances were observed in male infants; birth weight birth
      weight < 1500 g; Apgar score at five minutes < 7; weight-, length- and head
      circumference-for-age < -1 Z-score; and exclusively breastfeeding for < two
      months. CONCLUSIONS: Prematurity did not influence the psychomotor development of
      infants in this study population. Motor development was the most affected domain
      in the sample as a whole, especially due to biological factors. Investigations on
      child neuropsychomotor development should try to identify many determinant
      factors because of its multifactorial nature.

PMID- 23174870
TI  - Clinical and epidemiological characteristics of patients in the head and neck
      surgery department of a university hospital.
AB  - CONTEXT AND OBJECTIVES: Head and neck cancer is the fifth most common type of
      cancer worldwide. The objective of this study was to evaluate the clinical and
      epidemiological parameters in a head and neck surgery service. DESIGN AND
      SETTING: Cross-sectional study using patients' records, developed in
      otolaryngology and head and neck department of a university hospital in the
      northwest of the state of Sao Paulo. METHODS: A total of 995 patients in the head
      and neck surgery service between January 2000 and May 2010 were evaluated. The
      variables analyzed included: age, gender, skin color, tobacco and alcohol
      consumption, primary site, staging and histological tumor type, treatment and
      number of deaths. RESULTS: The disease was more frequent among men (79.70%),
      smokers (75.15%) and alcohol abusers (58.25%). The most representative sites were
      oral cavity (29.65%) and larynx (24.12%) for the primary site; squamous cell
      carcinoma (84.92%) was the most frequent histological type, and surgery (29.04%)
      and radiotherapy (14.19%) were the most common treatments. CONCLUSION: The cancer
      that affects patients assisted by the head and neck surgery service occurs mainly
      men, smokers and alcohol abusers, and the oral cavity and larynx are the sites
      with the highest incidence. The high rate of patients with stages III and IV
      indicates late diagnosis by the treatment centers, which reflects the need for
      prevention education campaigns for early diagnosis of the disease.

PMID- 23174871
TI  - Citation distribution profile in Brazilian journals of general medicine.
AB  - CONTEXT AND OBJECTIVE: Impact factors are currently the bibliometric index most
      used for evaluating scientific journals. However, the way in which they are used,
      for instance concerning the study or journal types analyzed, can markedly
      interfere with estimate reliability. This study aimed to analyze the citation
      distribution pattern in three Brazilian journals of general medicine. DESIGN AND
      SETTING: This was a descriptive study based on numbers of citations of scientific
      studies published by three Brazilian journals of general medicine. METHODS: The
      journals analyzed were Sao Paulo Medical Journal, Clinics and Revista da
      Associacao Medica Brasileira. This survey used data available from the Institute
      for Scientific Information (ISI) platform, from which the total number of papers
      published in each journal in 2007-2008 and the number of citations of these
      papers in 2009 were obtained. From these data, the citation distribution was
      derived and journal impact factors (average number of citations) were estimated.
      These factors were then compared with those directly available from the ISI
      Journal of Citation Reports (JCR). RESULTS: Respectively, 134, 203 and 192 papers
      were published by these journals during the period analyzed. The observed
      citation distributions were highly skewed, such that many papers had few
      citations and a small percentage had many citations. It was not possible to
      identify any specific pattern for the most cited papers or to exactly reproduce
      the JCR impact factors. CONCLUSION: Use of measures like "impact factors", which
      characterize citations through averages, does not adequately represent the
      citation distribution in the journals analyzed.

PMID- 23174872
TI  - A review of recent pediatric research published in Brazilian indexed journals.
AB  - This review surveys articles appertaining to the general field of pediatrics that
      have been published in Brazilian scientific periodicals over recent years. its
      main purpose was to bring to the attention of the readership of the Sao Paulo
      Medical Journal original contributions from specialty and non-specialty journals.
      we hope that this can be seen as a general scientific update for the readers. We
      have covered articles appearing in Brazilian ISI-indexed journals, following a
      PubMed search.

PMID- 23174873
TI  - Acrodermatitis due to zinc deficiency after combined vertical gastroplasty with
      jejunoileal bypass: case report.
AB  - CONTEXT: Nutritional complications may occur after bariatric surgery, due to
      restriction of food intake and impaired digestion or absorption of nutrients.
      CASE REPORT: After undergoing vertical gastroplasty and jejunoileal bypass, a
      female patient presented marked weight loss and protein deficiency. Seven months
      after the bariatric surgery, she presented dermatological features compatible
      with acrodermatitis enteropathica, as seen from the plasma zinc levels, which
      were below the reference values (34.4 mg%). The skin lesions improved
      significantly after 1,000 mg/day of zinc sulfate supplementation for one week.
      CONCLUSIONS: The patient's evolution shows that the multidisciplinary team
      involved in surgical treatment of obesity should take nutritional deficiencies
      into consideration in the differential diagnosis of skin diseases, in order to
      institute early treatment.

PMID- 23174874
TI  - Aphasia and herpes virus encephalitis: a case study.
AB  - CONTEXT: Meningoencephalitis early in life, of any etiology, is a risk factor for
      development of subsequent sequelae, which may be of physical, psychiatric,
      behavioral or cognitive origin. Anomia is a language abnormality frequently found
      in such cases, and other language deficits are rarely described. The aim of this
      study was to describe the cognitive and linguistic manifestations following a
      case of herpetic meningoencephalitis in a 13-year-old patient with eight years of
      schooling. CASE REPORT: The patient underwent a speech-language audiology
      assessment nine months after the neurological diagnosis. The battery of tests
      included the Montreal-Toulouse Language Assessment test protocol (MT Beta-86,
      modified), the description from the Cookie Theft task of the Boston Diagnostic
      Aphasia Examination (BDAE), an informal assessment of the patient's logical and
      mathematical reasoning, and the neuropsychological subtests from the WAIS-III
      scale, which assess working memory. The patient presented mixed aphasia,
      impairment of short-term memory and working memory, and dyscalculia. This case
      also presented severe cognitive and linguistic deficits. Prompt diagnosis is
      crucial, in order to enable timely treatment and rehabilitation of this
      neurological infection and minimize the cognitive deficits caused by the disease.

PMID- 23174875
TI  - Lack of association between Lewis phenotypes and ischemic heart disease.

PMID- 23174876
TI  - Sacrum osteosarcoma after pelvic radiation for uterine cervical cancer:
      highlighted issues.

PMID- 23174880
TI  - Lessons learned in shaping vaccine markets in low-income countries: a review of
      the vaccine market segment supported by the GAVI Alliance.
AB  - OBJECTIVES: The Global Alliance for Vaccines and Immunization (GAVI) anticipated
      that growing demand for new vaccines could sufficiently impact the vaccines
      market to allow low-income countries (LICs) to self-finance new vaccines. But the
      time required to lower vaccine prices was underestimated and the amount that
      prices would decline overestimated. To better understand how prices in the LIC
      vaccine market can be impacted, the vaccine market was retrospectively examined.
      DESIGN: GAVI archives and the published literature on the vaccine markets in LICs
      were reviewed for the purpose of identifying GAVI's early assumptions for the
      evolution of vaccine prices, and contrasting these retrospectively with actual
      outcomes. RESULTS: The prices in Phases I and II of GAVI-supported vaccines
      failed to decline to a desirable level within a projected 5-year timeframe. GAVI
      eligible countries were unable to sustain newly introduced vaccines without
      prolonged donor support. Two key lessons can be applied to future vaccine market
      shaping strategies: (1) accurate demand forecasting together with committed donor
      funding can increase supply to the LIC vaccines market, but even greater strides
      can be made to increase the certainty of purchase; and (2) the expected time to
      lower prices took much longer than 5 years; market competition is inherently
      linked to the development time for new vaccines--a minimum of 5-10 or more years.
      Other factors that can lower vaccine prices include: large-scale production or
      alternate financing mechanisms that can hasten vaccine price maturation.
      CONCLUSIONS: The impacts of competition on vaccine prices in the LIC new-vaccines
      market occurred after almost 10 years. The time for research and development,
      acquisition of technological know-how and to scale production must be accounted
      for to more accurately predict significant declines on vaccine prices. Alternate
      financing mechanisms and the use of purchase agreements should also be considered
      for lowering prices when planning new vaccine introductions.

PMID- 23174879
TI  - Access to medicines from a health system perspective.
AB  - Most health system strengthening interventions ignore interconnections between
      systems components. In particular, complex relationships between medicines and
      health financing, human resources, health information and service delivery are
      not given sufficient consideration. As a consequence, populations' access to
      medicines (ATM) is addressed mainly through fragmented, often vertical approaches
      usually focusing on supply, unrelated to the wider issue of access to health
      services and interventions. The objective of this article is to embed ATM in a
      health system perspective. For this purpose, we perform a structured literature
      review: we examine existing ATM frameworks, review determinants of ATM and define
      at which level of the health system they are likely to occur; we analyse to which
      extent existing ATM frameworks take into account access constraints at different
      levels of the health system. Our findings suggest that ATM barriers are complex
      and interconnected as they occur at multiple levels of the health system.
      Existing ATM frameworks only partially address the full range of ATM barriers. We
      propose three essential paradigm shifts that take into account complex and
      dynamic relationships between medicines and other components of the health
      system. A holistic view of demand-side constraints in tandem with consideration
      of multiple and dynamic relationships between medicines and other health system
      resources should be applied; it should be recognized that determinants of ATM are
      rooted in national, regional and international contexts. These are schematized in
      a new framework proposing a health system perspective on ATM. 

PMID- 23174881
TI  - Prediction of outcomes in patients with Ph+ chronic myeloid leukemia in chronic
      phase treated with nilotinib after imatinib resistance/intolerance.
AB  - The purpose was to assess predictive factors for outcome in patients with chronic
      myeloid leukemia (CML) in chronic phase (CML-CP) treated with nilotinib after
      imatinib failure. Imatinib-resistant and -intolerant patients with CML-CP (n=321)
      were treated with nilotinib 400 mg twice daily. Of 19 baseline patient and
      disease characteristics and two response end points analyzed, 10 independent
      prognostic factors were associated with progression-free survival (PFS). In the
      multivariate analysis, major cytogenetic response (MCyR) within 12 months,
      baseline hemoglobin >= 120 g/l, baseline basophils <4%, and absence of baseline
      mutations with low sensitivity to nilotinib were associated with PFS. A
      prognostic score was created to stratify patients into five groups (best group: 0
      of 3 unfavorable risk factors and MCyR by 12 months; worst group: 3 of 3
      unfavorable risk factors and no MCyR by 12 months). Estimated 24-month PFS rates
      were 90%, 79%, 67% and 37% for patients with prognostic scores of 0, 1, 2 and 3,
      respectively, (no patients with score of 4). Even in the presence of poor disease
      characteristics, nilotinib provided significant clinical benefit in patients with
      imatinib-resistant or -intolerant CML. This system may yield insight on the
      prognosis of patients.

PMID- 23174882
TI  - Role of early B-cell factor 1 (EBF1) in Hodgkin lymphoma.
AB  - A hallmark of classical Hodgkin lymphoma (cHL) is that the B-cell-derived Hodgkin
      and Reed-Sternberg (HRS) tumor cells have largely lost the B-cell-typical gene
      expression program. The factors causing this 'reprogramming' of HRS cells are
      only partly understood. As early B-cell factor 1 (EBF1), a major B-cell
      transcription factor, is downregulated in HRS cells, we analyzed whether this
      downregulation contributes to the lost B-cell phenotype and tested the
      consequences of EBF1 re-expression in cHL cell lines. EBF1 re-expression caused
      an upregulation of B-cell genes, such as CD19, CD79A and CD79B, although the B
      cell genes FOXO1 and PAX5 remained lowly expressed. The re-expression of CD19,
      CD79A and CD79B occurred largely without demethylation of promoter CpG motifs of
      these genes. In the cHL cell line L-1236 fitness decreased after EBF1 re
      expression. These data show that EBF1 has the ability to reintroduce part of the
      B-cell signature in cHL cell lines. Loss of EBF1 expression in HRS cells
      therefore contributes to their lost B-cell phenotype. Notably, in the cHL cell
      line KM-H2 destructive mutations were found in one allele of EBF1, indicating
      that genetic lesions may sometimes have a role in impairing EBF1 expression.

PMID- 23174883
TI  - Downregulation of specific miRNAs in hyperdiploid multiple myeloma mimics the
      oncogenic effect of IgH translocations occurring in the non-hyperdiploid subtype.
AB  - Currently, multiple myeloma (MM) patients are broadly grouped into a non
      hyperdiploid (nh-MM) group, highly enriched for IgH translocations, or into a
      hyperdiploid (h-MM) group, which is typically characterized by trisomies of some
      odd-numbered chromosomes. We compared the micro RNA (miRNA) expression profiles
      of these two groups and we identified 16 miRNAs that were downregulated in the h
      MM group, relative to the nh-MM group. We found that target genes of the most
      differentially expressed miRNAs are directly involved in the pathogenesis of MM;
      specifically, the inhibition of hsa-miR-425, hsa-miR-152 and hsa-miR-24, which
      are all downregulated in h-MM, leads to the overexpression of CCND1, TACC3, MAFB,
      FGFR3 and MYC, which are the also the oncogenes upregulated by the most frequent
      IgH chromosomal translocations occurring in nh-MM. Importantly, we showed that
      the downregulation of these specific miRNAs and the upregulation of their targets
      also occur simultaneously in primary cases of h-MM. These data provide further
      evidence on the unifying role of cyclin D pathways deregulation as the key
      mechanism involved in the development of both groups of MM. Finally, they
      establish the importance of miRNA deregulation in the context of MM, thereby
      opening up the potential for future therapeutic approaches based on this
      molecular mechanism.

PMID- 23174884
TI  - Gas-phase reactions of the atomic oxygen radical cation with halogenated
      compounds.
AB  - Rate constants and product distributions have been measured for the reactions of
      O(+)((4)S) with the methyl halides (CH(3)F, CH(3)Cl, CH(3)Br, CH(3)I) and three
      perfluorinated compounds (CF(4), SF(6), SF(5)CF(3)) at 300 K in a flowing
      afterglow-selected ion flow tube (FA-SIFT). The reactions occur with high
      efficiency, despite the necessity for spin conversion in some processes. The
      mechanisms include charge transfer, atom abstraction, and fragmentation
      reactions. Computational modeling was carried out to provide insight into these
      processes.

PMID- 23174885
TI  - Cu doped ZnO pellets: study of structure and Cu specific magnetic properties.
AB  - Cu doped ZnO polycrystalline pellets were synthesized with Cu concentrations
      varying from 2 to 10 wt% by a solid state reaction route (mixing of ZnO and CuO
      powders). Global magnetization measurements showed that all the samples were
      paramagnetic. Fitting the temperature-dependence of the magnetization to the
      Curie-Weiss law revealed the presence of an antiferromagnetic interaction between
      magnetic moments. Structural characterizations were carried out by x-ray
      diffraction and x-ray absorption spectroscopy (XAS) at the Cu K-edge. By
      analyzing the XAS data, we found that at low Cu content most of the Cu atoms
      substitute for Zn inside the ZnO wurtzite lattice, while for higher Cu
      concentrations some unreacted CuO remains segregated from the Zn(1-x)Cu(x)O solid
      solution. Element-specific magnetic measurements were carried out by x-ray
      magnetic circular dichroism (XMCD) and compared to the results of ab initio
      calculations. The XMCD signal at the Cu K-edge originates from magnetic moments
      localized at Cu sites and, by monitoring the magnetic field dependence, we concur
      that these moments are associated with a paramagnetic state.

PMID- 23174886
TI  - Complex anion inclusion compounds: flexible anion-exchange materials.
AB  - Copper chloropyrophosphate frameworks have been synthesised with a wide variety
      of complex inorganic anions trapped in a large, flexible, one-dimensional pore,
      with anions including chloride, bromide, phosphate and the complex metal halo
      anions PtCl(4)(2-), PdBr(4)(2-), CuCl(4)(2-) and AuCl(4)(-).

PMID- 23174887
TI  - The use of an Er:YAG laser to remove demineralized dentin and its influence on
      dentin permeability.
AB  - The purpose of this study was to analyze, correlate, and compare the
      demineralization and permeability of dentin remaining after caries removal with
      either an Er:YAG laser, a bur, or a curette. Thirty human dentin fragments were
      immersed in a demineralizing solution for 20 days and were randomly divided into
      three groups (n = 10) for the removal of the demineralized lesion. The groups
      were G1-Er:YAG laser (200 mJ/6 Hz; noncontact at 12 mm; spot: 0.63 mm), G2-Bur,
      and G3-Curette. The specimens were then immersed in a 10% copper sulfate
      solution, then in a 1% dithiooxamide alcoholic solution for 30 min and kept in
      ammonia vapor for 7 days. Next, the specimens were examined with optical
      microscopy. The amount of demineralized dentin and the level of copper ion
      infiltration in the dentin were quantified in MUm using Axion Vision software.
      Data were analyzed with the Kruskal-Wallis test (p < 0.05) and Pearson's
      Correlation test. The analysis revealed no significant differences between the
      three caries removal methods in terms of their capacity to remove demineralized
      tissue (G1: 10.6 MUm; G2: 8.4 MUm; G3: 11 MUm), although the laser removal
      generated more tissue permeability than the others methods (G1: 17.6 MUm; G2: 6.6
      MUm; G3: 5.5 MUm). The correlation between the remaining demineralized dentin and
      the dentin permeability was moderate for the conventional methods and higher for
      the Er:YAG laser. It can therefore be concluded that the laser produced an
      increase in permeability that was directly proportional to the amount of
      demineralized tissue removal.

PMID- 23174888
TI  - Suppression of metastasis of intravenously-inoculated B16/F10 melanoma cells by
      the novel ginseng-derived ingredient, gintonin: involvement of autotaxin
      inhibition.
AB  - Ginseng has been used for cancer prevention. However, little is known about its
      active components and the molecular mechanisms underlying its effects. Recently,
      we isolated a unique lysophosphatidic acid (LPA) receptor ligand, gintonin.
      Gintonin contains approximately 9.5% LPA, mainly LPA C18:2. Autotaxin (ATX) is
      responsible for metastasis by overproducing LPA in cancers. However, LPA,
      particularly LPA C18:2, is a strong negative feedback ATX inhibitor. It is
      unknown whether gintonin inhibits ATX activity and whether gintonin-induced ATX
      inhibition is coupled with antimetastatic activity. In this study, we examined
      whether gintonin and LPA C18:2 inhibit ATX activity and metastasis-related
      cellular activities in melanoma cells. We found that gintonin and LPA C18:2
      inhibited the purified and secreted ATX activity from melanoma cells in a
      concentration-dependent manner. Gintonin also inhibited cell migration with a
      minimal inhibition of cell growth. The oral administration of gintonin or LPA
      C18:2 inhibited lung metastasis induced by tail-vein inoculations of melanoma
      cells. Moreover, the oral administration of gintonin significantly suppressed the
      tumor growth induced by subcutaneous grafts of melanoma cells. A histological
      analysis showed that the oral administration of gintonin reduced tumor necrosis,
      the pleomorphism of tumor cells, tumor cell mitosis and angiogenesis. The present
      study demonstrates that the gintonin-induced inhibition of ATX activity may be
      the molecular basis of ginseng-induced antimetastatic and antitumor activities.

PMID- 23174889
TI  - The first ratiometric fluorescent probes for aminopeptidase N cell imaging.
AB  - In the current paper, three activity-based colorimetric and ratiometric
      fluorescent probes based on a naphthalimide fluorophore were well designed and
      synthesized, which can be recognized and hydrolyzed by aminopeptidase N (APN) at
      both the enzymatic and cellular level by following the fluorescent emission
      wavelength change from blue to green light. As a result, these molecules were
      successfully identified as the first ratiometric fluorescent probes for APN cell
      imaging.

PMID- 23174890
TI  - An electrostatically crosslinked chitosan hydrogel as a  drug carrier.
AB  - Considerable efforts have been devoted to control and maintain the sustained
      release of proteins. In this experiment, we used bovine serum albumin-fluorescein
      isothiocyanate (BSA-FITC) as a model protein to explore the potential utility of
      a chitosan and glycerol phosphate disodium salt (GP) hydrogel as a protein drug
      depot. The mixing of chitosan and GP solutions (0, 10, 20 and 30 wt%) formed a
      liquid at room temperature. At 37 &#176;C, however, the chitosan/GP solutions
      formed hydrogels through an electrostatic crosslinking process. This
      electrostatic interaction between the chitosan, cationic amine group, and GP,
      anionic phosphate group, was confirmed by the changes of zeta potentials and
      particle sizes of this solution. The electrostatic interaction depended both on
      the  GP ratios in chitosan and the incubation time of chitosan/GP solutions.
      Furthermore,  BSA-FITC-loaded chitosan/GP hydrogels were examined for their
      ability as potential depots for the BSA drugs. Hence, when observed, the BSA-FITC
      loaded chitosan/GP hydrogels showed an in vitro sustained release profile of BSA
      up to 14 days. Collectively, our results show that the chitosan/GP hydrogels
      described here, can serve as depots for BSA drugs.

PMID- 23174891
TI  - 5'-Chloro-5'-deoxy-(+/-)-ENBA, a potent and selective adenosine A(1) receptor
      agonist, alleviates neuropathic pain in mice through functional glial and
      microglial changes without affecting motor or cardiovascular functions.
AB  - This study was undertaken in order to investigate the effect of chronic treatment
      with 5&#8242;-chloro-5&#8242;-deoxy-(&#177;)-ENBA, a potent and highly selective
      agonist of human adenosine A(1) receptor, on thermal hyperalgesia and mechanical
      allodynia in a mouse model of neuropathic pain, the Spared Nerve Injury (SNI) of
      the sciatic nerve. Chronic systemic administration of 5&#8242;-chloro-5&#8242;
      deoxy-(&#177;)-ENBA (0.5 mg/kg, i.p.) reduced both mechanical allodynia and
      thermal hyperalgesia 3 and 7 days post-SNI, in a way prevented by DPCPX (3 mg/kg,
      i.p.), a selective A(1) adenosine receptor antagonist, without exerting any
      significant change on the motor coordination or arterial blood pressure. In
      addition, a single intraperitoneal injection of 5&#8242;-chloro-5&#8242;-deoxy
      (&#177;)-ENBA (0.5 mg/kg, i.p.) 7 days post-SNI also reduced both symptoms for at
      least two hours. SNI was associated with spinal changes in microglial activation
      ipsilaterally to the nerve injury. Activated, hypertrophic microglia were
      significantly reduced by 5&#8242;-chloro-5&#8242;-deoxy-(&#177;)-ENBA chronic
      treatment. Our results demonstrated an involvement of adenosine A(1) receptor in
      the amplified nociceptive thresholds and in spinal glial and microglial changes
      occurred in neuropathic pain, without affecting motor coordination or blood
      pressure. Our data suggest a possible use of adenosine A(1) receptor agonist in
      neuropathic pain symptoms.

PMID- 23174892
TI  - Synthesis and antiproliferative activity of ammonium and imidazolium ionic
      liquids against T98G brain cancer cells.
AB  - Four ammonium and imidazolium ionic liquids (ILs) have been synthesized and
      screened against the T98G cell line (brain cancer) and HEK normal cells.
      Treatment induced metabolic cell death (MTT), growth inhibition, clonogenic
      inhibition were studied as cellular response parameters. Treatment with ILs
      enhanced growth inhibition and cell death in a concentration dependent manner in
      both the T98G and HEK cell lines. At higher concentrations (>0.09 mg/mL) the
      cytotoxic effects of the ILs were highly significant. An inhibitory effect on
      clonogenic capacity was also observed after cell treatment. Amongst all ILs; IL 4
      (BMIMCl) exhibited potent activity against T98G brain cancer cells. Despite
      potent in-vitro activity, all ILs exhibited less cytotoxicity against the normal
      human HEK cells at all effective concentrations.

PMID- 23174893
TI  - Generation of the first structure-based pharmacophore model containing a
      selective "zinc binding group" feature to identify potential glyoxalase-1
      inhibitors.
AB  - Within this study, a unique 3D structure-based pharmacophore model of the enzyme
      glyoxalase-1 (Glo-1) has been revealed. Glo-1 is considered a zinc metalloenzyme
      in which the inhibitor binding with zinc atom at the active site is crucial. To
      our knowledge, this is the first pharmacophore model that has a selective feature
      for a "zinc binding group" which has been customized within the structure-based
      pharmacophore model of Glo-1 to extract ligands that possess functional groups
      able to bind zinc atom solely from database screening. In addition, an extensive
      2D similarity search using three diverse similarity techniques (Tanimoto, Dice,
      Cosine) has been performed over the commercially available "Zinc Clean Drug-Like
      Database" that contains around 10 million compounds to help find suitable
      inhibitors for this enzyme based on known inhibitors from the literature. The
      resultant hits were mapped over the structure based pharmacophore and the
      successful hits were further docked using three docking programs with different
      pose fitting and scoring techniques (GOLD, LibDock, CDOCKER). Nine candidates
      were suggested to be novel Glo-1 inhibitors containing the "zinc binding group"
      with the highest consensus scoring from docking.

PMID- 23174894
TI  - Palladium-catalyzed multicomponent synthesis of 2-imidazolines from imines and
      acid chlorides.
AB  - We describe the palladium-catalyzed multicomponent synthesis of 2-imidazolines.
      This reaction proceeds via the coupling of imines, acid chlorides and carbon
      monoxide to form imidazolinium carboxylates, followed by a decarboxylation.
      Decarboxylation in CHCl(3) is found to result in a mixture of imidazolinium and
      imidazolium salts. However, the addition of benzoic acid suppresses
      aromatization, and generates the trans-disubstituted imidazolines in good yield.
      Combining this reaction with subsequent nitrogen deprotection provides an overall
      synthesis of imidazolines from multiple available building blocks.

PMID- 23174895
TI  - Red ginseng marc oil inhibits iNOS and COX-2 via NFkappaB and p38 pathways in LPS
      stimulated RAW 264.7 macrophages.
AB  - In this study, we investigated the anti-inflammatory effects of red ginseng marc
      oil (RMO) in the RAW 264.7 macrophage cell line. RMO was prepared by a
      supercritical CO(2) extraction of waste product generated after hot water
      extraction of red ginseng. RMO significantly inhibited the production of
      oxidative stress molecules such as nitric oxide and reactive oxygen species in
      lipopolysaccharide (LPS)-activated RAW 264.7 cells. Levels of inflammatory
      targets including prostaglandin E2, tumor necrosis factor-&#945;, interleukin 
      (IL)-1&#946; and IL-6 were also reduced after the treatment with RMO. In
      addition, RMO diminished the expressions of inducible nitric oxide synthase and
      cyclooxygenase 2 at both mRNA and protein levels. Blockade of nuclear
      translocation of the p65 subunit of nuclear factor &#954;B (NF&#954;B) was also
      observed after the treatment of RMO. Furthermore, RMO decreased the
      phosphorylations of p38 mitogen-activated protein kinase (MAPK) and its upstream
      kinases including MAPK kinases 3/6 (MKK3/6) and TAK 1 (TGF-&#946; activated
      kinase 1). Gas chromatographic analysis on RMO revealed that RMO contained about
      10% phytosterols including sitosterol, stigmasterol and campesterol which may
      contribute to the anti-inflammatory properties of RMO. Taken together, these
      results suggest that the  anti-inflammatory effect of RMO in LPS-induced RAW
      264.7 macrophages could be associated with the inhibition of NF&#954;B
      transcriptional activity, possibly via blocking the p38 MAPK pathway.

PMID- 23174896
TI  - Spiroheterocyclization of methyl 1-aryl-3-cinnamoyl-4,5-dioxo-4,5-dihydro-1H
      pyrrole-2-carboxylates by the action of 3-(arylamino)-1H-inden-1-ones.
AB  - Methyl 1-aryl-3-cinnamoyl-4,5-dioxo-4,5-dihydro-1H-pyrrole-2-carboxylates
      interact with 3-(arylamino)-1H-inden-1-ones to give the corresponding 1,1'-diaryl
      3'-cinnamoyl-4'-hydroxy-1H-spiro[indeno[1,2-b]pyrrole-3,2'-pyrrole]-2,4,5'(1'H)
      triones in good yields.

PMID- 23174897
TI  - Headspace solid-phase microextraction gas  chromatography-mass spectrometry and
      gas  chromatography-olfactometry analysis of  volatile compounds in pineapple
      breads.
AB  - Sensorial analysis of pineapple breads (conventionally baked, Cpb; fully baked
      frozen, Fpb and partially baked, Ppb) showed no significant differences in terms
      of aroma and taste. On the contrary, the scores for the overall quality between
      the partially baked and conventionally baked breads showed significant (p < 0.05)
      differences. At the same time, headspace analysis using a solid-phase
      microextraction (SPME) method identified 59 volatile compounds. The results of
      the aroma extracts dilution analysis (AEDA) revealed 19 most odour-active
      compounds with FD factors in the range of 32-128 as the key odourants of the
      pineapple breads. Further analysis of the similarities and differences between
      the pineapple breads in terms of the key odourants were carried out by the
      application of PLS-DA and PLS-regression coefficients. Results showed that Ppb
      exhibited strong positive correlations with most of the volatile- and non
      volatile compounds, while the Cpb showed significant positive correlations with
      hexanal and 4-hydroxy-2,5-dimethyl-3(2H)-furanone, and the Fpb had strong
      positive correlations with lactic acid, benzoic acid, benzaldehyde and ethyl
      propanoate.

PMID- 23174898
TI  - Lipases as tools in the synthesis of prodrugs from racemic 9-(2,3
      dihydroxypropyl)adenine.
AB  - Lipases from Geotrichum candidum 4013 (extracellular lipase and cell-bound
      lipase) were immobilized by adsorption on chitosan beads. The enzyme preparations
      were tested in the synthesis of ester prodrugs from racemic 9-(2,3
      dihydroxypropyl)adenine in dimethylformamide with different vinyl esters
      (acetate, butyrate, decanoate, laurate, palmitate). The transesterification
      activities of these immobilized enzymes were compared with commercially available
      lipases (lipase from hog pancreas, Aspergillus niger, Candida antarctica,
      Pseudomonas fluorescens). Lipase from Candida antarctica was found to be the most
      efficient enzyme regarding chemical yield of the desired products, while
      transesterification by lipase from Aspergillus niger resulted in lower yields.

PMID- 23174899
TI  - Oligonucleotide-peptide conjugates: solid-phase synthesis under acidic conditions
      and use in ELISA assays.
AB  - Here we used solid-phase methods to prepare oligonucleotides carrying fibrin/
      filaggrin citrullinated peptides. Post-synthetic conjugation protocols were
      successfully applied for the synthesis of oligonucleotides carrying small
      peptides. A stepwise protocol using acid treatment for the final deprotection
      allowed the preparation of polypyrimidine oligonucleotides carrying longer and
      arginine-rich peptides. An ELISA-based test using  the oligonucleotide
      citrullinated peptide conjugates was developed for the detection of  anti
      citrullinated protein/peptide antibodies in human serum from rheumatoid 
      arthritis patients.

PMID- 23174900
TI  - Influence of nonpolar substances on the extraction efficiency of six alkaloids in
      Zoagumhwan investigated by ultra performance liquid chromatography and photodiode
      array detection.
AB  - A reverse phase ultra performance liquid chromatography and photodiode array
      (UPLC-PDA) detection method was established for the determination of six
      alkaloids in Zoagumhwan (ZGW), and further for investigating the influence of
      nonpolar substances on the extraction efficiency of these alkaloids. The method
      was based on a BEH C(18) (50 mm * 2.1 mm, 1.7 MUm) column and mobile phase of
      aqueous phosphoric acid and acetonitrile including 0.05% buffer solution under
      gradient elution. ZGW samples of ZGW I, II, III and IV were obtained and prepared
      by pre-processing the crude materials of Coptidis rhizoma and Evodiae fructus
      using four technologies, namely direct water decoction, removal of nonpolar
      substances in Evodiae fructus by supercritical fluid extraction (SFE), removal of
      nonpolar substances in ZGW by SFE and removal of nonpolar substances in ZGW by
      steam distillation. The developed and validated UPLC-PDA method was precise,
      accurate and sensitive enough based on the facts that the six alkaloids showed
      good regression (r > 0.9998), the limit of detections and quantifications for six
      alkaloids were less than 28.8 and 94.5 ng/mL, respectively, and the recovery was
      in the range of 98.56%-103.24%. The sequence of the total contents of six
      alkaloids in these samples was ZGW II > ZGW IV > ZGW III > ZGW I. ZGW II, in
      which nonpolar substances, including essential oils, were firstly removed from
      Evodiae fructus by SFE, had the highest content of the total alkaloids,
      indicating that extraction efficiency of the total alkaloids could be remarkably
      increased after Evodiae fructus being extracted by SFE.

PMID- 23174901
TI  - An efficient one-pot synthesis of pyrano[3,2-c]quinolin-2,5-dione derivatives
      catalyzed by L-proline.
AB  - A series of 4-aryl-6-methyl-3,4-dihydro-2H-pyrano[3,2-c]quinolin-2,5(6H)-diones
      were synthesized via the three-component reactions of aromatic aldehydes, 4
      hydroxy-1-methylquinolin-2(1H)-one, and Meldrum's acid catalyzed by L-proline.
      The structures of the products were identified by spectroscopic analysis. A
      mechanism for this three-component reaction catalyzed by L-proline was proposed.

PMID- 23174902
TI  - Efficient preparation of &#945;-ketoacetals.
AB  - The Weinreb amides 2a,b were prepared from the alpha,alpha-dimethoxyacetic acids
      1c,d. A number of representative nucleophilic additions (RMgX and RLi) on 2
      afforded alpha-ketoacetals 3a-j in 70-99% yield. These compounds represent a
      versatile arrangement of functional groups of significant synthetic value, as
      demonstrated in the synthesis of (+/-)-salbutamol.

PMID- 23174903
TI  - Novel rearrangements in the reactions directed toward preparation of spiro-N,N
      ketals: reactions of naphthalene-1,8-diamine with ninhydrin and isatin.
AB  - Spiro-N,N-ketal 5, consisting of a phthaloperine heterocyclic ring and a
      naphtha[1,8-ef][1,4]diazepine ring, was obtained along with spiro-N,N-ketal 2 via
      2,2-condensation in the reaction of ninhydrin with naphthalene-1,8-diamine.
      Their molecular structures were elucidated by X-ray crystal structural analysis.
      Aside from these spiro compounds, the diazapleiadiene compound 3 formed by 1,2
      condensation and the  1,4-isoquinolinedione compound 4 arising from ring
      expansion were isolated. When isatin was reacted with naphthalene-1,8-diamine,
      spiro-N,N-ketal 6 and the two 1H-perimidine-based compounds 7 and 8 were
      isolated. Compound 8 was revealed to undergo a fast dynamic prototropic
      tautomerization in solution. Plausible mechanisms of the formation of the
      products are proposed.

PMID- 23174904
TI  - BCR-ABL mediated repression of miR-223 results in the activation of MEF2C and
      PTBP2 in chronic myeloid leukemia.

PMID- 23174905
TI  - Enhancement of tumor-associated antigen-specific T cell responses by
      radiofrequency ablation of hepatocellular carcinoma.
AB  - Radiofrequency ablation (RFA) is one of the treatments for hepatocellular
      carcinoma (HCC) and is known to enhance host immune response. However, the
      epitopes to which enhanced immune responses occur, the impact on patient
      prognosis, and the functions and phenotype of T cells induced are still unclear.
      To address these issues, we analyzed immune responses before and after RFA in 69
      HCC patients using 11 tumor-associated antigen (TAA)-derived peptides that we
      identified to be appropriate to analyze HCC-specific immune responses. The immune
      responses were analyzed using enzyme-linked immunospot (ELISPOT) assay and
      tetramer assays using peripheral blood mononuclear cells. An increase in the
      number of TAA-specific T cells detected by interferon-gamma ELISPOT assays
      occurred in 62.3% of patients after RFA. The antigens and their epitope to which
      enhanced T cell responses occur were diverse, and some of them were newly
      induced. The number of TAA-specific T cells after RFA was associated with the
      prevention of HCC recurrence, and it was clarified to be predictive of HCC
      recurrence after RFA by univariate and multivariate analyses. The number of TAA
      specific T cells after RFA was inversely correlated with the frequency of CD14+
      HLA-DR(-/low) myeloid-derived suppressor cells (MDSCs). The modification of T
      cell phenotype was observed after RFA. The number of TAA-specific T cells at 24
      weeks after RFA was decreased. CONCLUSION: Although RFA can enhance various TAA
      specific T cell responses and the T cells induced contribute to the HCC
      recurrence-free survival of patients, besides immunosuppression by MDSCs, the
      memory phenotype and lifetime of TAA-specific T cells are not sufficient to
      prevent HCC recurrence completely. Additional treatments by vaccine or
      immunomodulatory drugs might be useful to improve the immunological effect of
      RFA.

PMID- 23174906
TI  - Analysis of serum alpha-fetoprotein-L3% and des-gamma carboxyprothrombin markers
      in cases with misleading hepatocellular carcinoma total alpha-fetoprotein levels.
AB  - Serum fraction of alpha-fetoprotein L3 (AFP-L3%) and des-gamma carboxyprothrombin
      (DCP) are proposed serum markers for the diagnosis of hepatocellular carcinoma
      (HCC). We evaluated their performance in two patient populations with total AFP
      levels non-diagnostic for HCC. From a cohort of 150 consecutive patients with
      HCC, 60 patients with total AFP <200 ng/ml were identified. Additionally, 50
      patients with elevated AFP and no radiological evidence of HCC, for at least one
      year of follow-up, were included. AFP-L3% and DCP were measured by the Liquid
      Phase Binding Assay System (LiBASys). In cases where AFP-L3% was undetectable, a
      more sensitive method based on-chip electrokinetic reaction was applied. AFP-L3%
      was found to be positive in 22 (36.7%) of patients with HCC and 6 (12%) of non
      HCC patients. DCP was found to be positive in 26 patients with HCC (43%) and in
      none of the non-HCC patients. Thirty-six out of sixty (60%) patients with HCC
      were positive for either AFP-L3% or DCP. With the on-chip technology, AFP-L3% was
      found to be positive in 10 patients with HCC and in 5 patients without HCC, who
      tested negative by LiBASys. The final sensitivity of combined AFP, AFP-L3% and
      DCP testing, in the entire cohort of patients with HCC, was 84%. The specificity
      of AFP-L3% and DCP in the studied population was 78.5 and 100%, respectively. The
      addition of AFP-L3% and DCP increased the sensitivity and specificity of total
      serum AFP for the diagnosis of HCC. The on chip AFP-L3% assay was more sensitive
      but less specific compared to LiBASys.

PMID- 23174907
TI  - Discrete nature of EpCAM+ and CD90+ cancer stem cells in human hepatocellular
      carcinoma.
AB  - Recent evidence suggests that hepatocellular carcinoma (HCC) is organized by a
      subset of cells with stem cell features (cancer stem cells; CSCs). CSCs are
      considered a pivotal target for the eradication of cancer, and liver CSCs have
      been identified by the use of various stem cell markers. However, little
      information is known about the expression patterns and characteristics of marker
      positive CSCs, hampering the development of personalized CSC-targeted therapy.
      Here, we show that CSC markers EpCAM and CD90 are independently expressed in
      liver cancer. In primary HCC, EpCAM+ and CD90+ cells resided distinctively, and
      gene-expression analysis of sorted cells suggested that EpCAM+ cells had features
      of epithelial cells, whereas CD90+ cells had those of vascular endothelial cells.
      Clinicopathological analysis indicated that the presence of EpCAM+ cells was
      associated with poorly differentiated morphology and high serum alpha-fetoprotein
      (AFP), whereas the presence of CD90+ cells was associated with a high incidence
      of distant organ metastasis. Serial xenotransplantation of EpCAM+ /CD90+ cells
      from primary HCCs in immune-deficient mice revealed rapid growth of EpCAM+ cells
      in the subcutaneous lesion and a highly metastatic capacity of CD90+ cells in the
      lung. In cell lines, CD90+ cells showed abundant expression of c-Kit and in vitro
      chemosensitivity to imatinib mesylate. Furthermore, CD90+ cells enhanced the
      motility of EpCAM+ cells when cocultured in vitro through the activation of
      transforming growth factor beta (TGF-beta) signaling, whereas imatinib mesylate
      suppressed TGFB1 expression in CD90+ cells as well as CD90+ cell-induced motility
      of EpCAM+ cells. CONCLUSION: Our data suggest the discrete nature and potential
      interaction of EpCAM+ and CD90+ CSCs with specific gene-expression patterns and
      chemosensitivity to molecular targeted therapy. The presence of distinct CSCs may
      determine the clinical outcome of HCC.

PMID- 23174908
TI  - Lipid composition of Castanea sativa Mill. and Aesculus hippocastanum fruit oils.
AB  - BACKGROUND: Sweet and horse chestnut fruit contain carbohydrates, fibers,
      proteins, lipids, vitamins, glycosides and coumarin. The lipids are rich in
      biologically active substances as fatty acids, phospholipids, sterols and
      tocopherols. The fruit has been used as food, and for medicinal purposes to treat
      inflammatory and vascular problems. RESULTS: The fruits of sweet and horse
      chestnut contain 20 and 81 g kg(-1) glyceride oil respectively. The content of
      phospholipids in the oils was 49 and 3 g kg(-1). Sterols were found to be 8 and
      12 g kg(-1). In the tocopherol fraction (1920 and 627 mg kg(-1)) gamma-tocopherol
      predominated in the sweet chestnut oil (927 g kg(-1)); gamma-tocopherol (591 g
      kg(-1)) and alpha-tocopherol (402 g kg(-1)) in horse chestnut oil. Palmitic,
      oleic and linoleic acids predominated in the triacylglycerols. Higher quantities
      of palmitic and oleic acids were established in the phospholipids and sterol
      esters. CONCLUSION: The fruits of horse and sweet chestnut have a close lipid
      composition. The oils are rich in essential fatty acids, such as linoleic and
      linolenic, as well as biologically active substances: phospholipids, sterols and
      tocopherols. This fact determines the good food value of sweet chestnut fruit and
      the possibilities for use of horse chestnuts in pharmacy and for technical
      purposes.

PMID- 23174909
TI  - Magnetocaloric effect in M-pyrazole-[Nb(CN)(8)] (M = Ni, Mn) molecular compounds.
AB  - We report a study of magnetocaloric effect (MCE) in cyanido-bridged
      {[M(II)(pyrazole)(4)](2)[Nb(IV)(CN)(8)].4H(2)O}(n) molecular compounds where M =
      Ni, Mn, pyrazole = C(3)H(4)N(2). The substances show a sharp phase transition to
      a long range magnetically ordered state, with ferromagnetic coupling between M
      and Nb sublattices in the case of the Ni-based sample 1 (T(c) = 13.4 K) and
      ferrimagnetic coupling for the Mn-based sample 2 (T(c) = 23.8 K). The magnetic
      entropy change DeltaS due to applied field change DeltaH as a function of
      temperature was determined by the magnetization and heat capacity measurements.
      The maximum value of DeltaS at MU(0)DeltaH = 5 T is 6.1 J mol(-1) K(-1) (5.9 J
      kg(-1) K(-1)) for 1 at T = 14 K and 6.7 J mol(-1) K(-1) (6.5 J kg(-1) K(-1)) for
      2 at T = 25 K. MCE data at different applied fields have been presented as one
      universal curve, which confirms magnetic transitions in 1 and 2 to be of second
      order. The temperature dependences of the n exponent characterizing the
      dependence of DeltaS on DeltaH have been obtained. The n(T(c)) values, consistent
      with the shape of the magnetization curves, pointed to the 3D Heisenberg
      behaviour for 2 and some anisotropy, probably of the XY type, for 1. The
      (H/T(c))(2/3) dependence of the maximum entropy change has been tested in the
      ferrimagnetic Mn(2)-L-[Nb(CN)(8)] (L = C(3)H(4)N(2), C(4)H(4)N(2)) series.

PMID- 23174911
TI  - In vivo assessment of human burn scars through automated quantification of
      vascularity using optical coherence tomography.
AB  - In scars arising from burns, objective assessment of vascularity is important in
      the early identification of pathological scarring, and in the assessment of
      progression and treatment response. We demonstrate the first clinical assessment
      and automated quantification of vascularity in cutaneous burn scars of human
      patients in vivo that uses optical coherence tomography (OCT). Scar
      microvasculature was delineated in three-dimensional OCT images using speckle
      decorrelation. The diameter and area density of blood vessels were automatically
      quantified. A substantial increase was observed in the measured density of
      vasculature in hypertrophic scar tissues (38%) when compared against normal,
      unscarred skin (22%). A proliferation of larger vessels (diameter>=100  MUm) was
      revealed in hypertrophic scarring, which was absent from normal scars and normal
      skin over the investigated physical depth range of 600 MUm. This study
      establishes the feasibility of this methodology as a means of clinical monitoring
      of scar progression.

PMID- 23174910
TI  - Cigarette smoke condensate induces differential expression and promoter
      methylation profiles of critical genes involved in lung cancer in NL-20 lung
      cells in vitro: short-term and chronic exposure.
AB  - Establishing early diagnostic markers of harm is critical for effective
      prevention programs and regulation of tobacco products. This study examined
      effects of cigarette smoke condensate (CSC) on expression and promoter
      methylation profile of critical genes (DAPK, ECAD, MGMT, and RASSF1A) involved in
      lung cancer development in different human lung cell lines. NL-20 cells were
      treated with 0.1-100 MUg/ml of CSC for 24 to 72 hrs for short-term exposures.
      DAPK expression or methylation status was not significantly affected. However,
      CSC treatment resulted in changes in expression and promoter methylation profile
      of ECAD, MGMT, and RASSF1A. For chronic studies, cells were exposed to 1 or 10
      MUg/ml CSC up to 28 days. Cells showed morphological changes associated with
      transformation and changes in invasion capacities and global methylation status.
      This study provides critical data suggesting that epigenetic changes could serve
      as an early biomarker of harm due to exposure to cigarette smoke.

PMID- 23174913
TI  - Hyaluronated fullerenes with photoluminescent and antitumoral activity.
AB  - Hyaluronated fullerene has strong near-infrared (NIR) fluorescence intensity
      without labelling with any fluorophores or isotopes. This fullerene allowed high
      resolution fluorescent imaging of tumor sites in vivo and resulted in a
      significant regression of HCT-116 tumors.

PMID- 23174914
TI  - Anatomy, ultrastructure, and secretory activity of the floral nectaries in
      Swietenia macrophylla (Meliaceae).
AB  - PREMISE OF THE STUDY: While mahogany (Swietenia macrophylla) is one of the most
      important forest species in the Amazon region, little is known about its
      reproductive biology. Knowledge about the nectary structure and dynamics of
      nectar production of this species represent a key step toward understanding its
      relationship with pollinators. * METHODS: Mahogany tree floral buds and flowers
      in anthesis were collected, fixed, and processed for study by light and
      transmission and scanning electron microscopy. The chemical composition of nectar
      and the nectary pigments was also studied. * KEY RESULTS: Both staminate and
      pistillate flowers have nectaries, which contain a papillose epidermis and
      stomata. The nectariferous tissue is parenchymatous, with the cell cytoplasm
      primarily containing mitochondria and plastids. Secretory activity initiates at
      the beginning of anthesis, which occurs at nightfall. Flowers undergoing anthesis
      become structurally modified, with starch grains in the plastids disappearing.
      The number of plastoglobuli in the plastids also increases when nectaries change
      color from pale yellow to intense red. Pistillate and staminate flowers produce
      meager nectar rewards. * CONCLUSIONS: Changes in plastoglobuli number seem to be
      related to an increase in carotenes and color changes during anthesis. Carotenes
      can be linked to the protection of the plant against oxidative stress, which
      results from secretory activities. Nectary color has a limited role as a
      pollinator attractant. Floral rewards comprise small nectar droplets in both
      flower types, in addition to a few pollen grains in staminate flowers. These
      meager rewards are probably adapted to attract small generalist insects.

PMID- 23174912
TI  - Role of Kras status in patients with metastatic colorectal cancer receiving first
      line chemotherapy plus bevacizumab: a TTD group cooperative study.
AB  - BACKGROUND: In the MACRO study, patients with metastatic colorectal cancer (mCRC)
      were randomised to first-line treatment with 6 cycles of capecitabine and
      oxaliplatin (XELOX) plus bevacizumab followed by either single-agent bevacizumab
      or XELOX plus bevacizumab until disease progression. An additional retrospective
      analysis was performed to define the prognostic value of tumour KRAS status on
      progression-free survival (PFS), overall survival (OS) and response rates.
      METHODOLOGY/PRINCIPAL FINDINGS: KRAS data (tumour KRAS status and type of
      mutation) were collected by questionnaire from participating centres that
      performed KRAS analyses. These data were then cross-referenced with efficacy data
      for relevant patients in the MACRO study database. KRAS status was analysed in
      394 of the 480 patients (82.1%) in the MACRO study. Wild-type (WT) KRAS tumours
      were found in 219 patients (56%) and mutant (MT) KRAS in 175 patients (44%).
      Median PFS was 10.9 months for patients with WT KRAS and 9.4 months for patients
      with MT KRAS tumours (p=0.0038; HR: 1.40; 95% CI:1.12-1.77). The difference in OS
      was also significant: 26.7 months versus 18.0 months for WT versus MT KRAS,
      respectively (p=0.0002; HR: 1.55; 95% CI: 1.23-1.96). Univariate and multivariate
      analyses showed that KRAS was an independent variable for both PFS and OS.
      Responses were observed in 126 patients (57.5%) with WT KRAS tumours and 76
      patients (43.4%) with MT KRAS tumours (p=0.0054; OR: 1.77; 95% CI: 1.18-2.64).
      CONCLUSIONS/SIGNIFICANCE: This analysis of the MACRO study suggests a prognostic
      role for tumour KRAS status in patients with mCRC treated with XELOX plus
      bevacizumab. For both PFS and OS, KRAS status was an independent factor in
      univariate and multivariate analyses.

PMID- 23174915
TI  - Analysis of magnetic gradients to study gravitropism.
AB  - PREMISE OF THE STUDY: Gravitropism typically is generated by dense particles that
      respond to gravity. Experimental stimulation by high-gradient magnetic fields
      provides a new approach to selectively manipulate the gravisensing system.
      METHODS: The movement of corn, wheat, and potato starch grains in suspension was
      examined with videomicroscopy during parabolic flights that generated 20 to 25 s
      of weightlessness. During weightlessness, a magnetic gradient was generated by
      inserting a wedge into a uniform, external magnetic field that caused repulsion
      of starch grains. The resultant velocity of movement was compared with the
      velocity of sedimentation under 1 g conditions. RESULTS: The high-gradient
      magnetic fields repelled the starch grains and generated a force of at least 0.6
      g. Different wedge shapes significantly affected starch velocity and
      directionality of movement. CONCLUSIONS: Magnetic gradients are able to move
      diamagnetic compounds under weightless or microgravity conditions and serve as
      directional stimulus during seed germination in low-gravity environments. Further
      work can determine whether gravity sensing is based on force or contact between
      amyloplasts and statocyte membrane system.

PMID- 23174917
TI  - End-organ protection in cardiac surgery.
AB  - Mortality and morbidity postcardiac surgery with cardiopulmonary bypass (CPB)
      remain relative stable over the last decades, while the number of patients with
      increased comorbidity and more complex cardiac disease increases. Nevertheless,
      end-organ dysfunction and/or failure remain an issue. Multiple perioperative
      variables, such as non-optimal oxygen delivery, manipulation of the aorta,
      hyperlactatemia, type of anesthesia, surgical procedure and myocardial protection
      can be hold responsible for end-organ failure postcardiac surgery. However, it
      becomes more and more evident that also pre-existing factors, such as metabolic
      syndrome, renal insufficiency, hypertension, stroke and infection exacerbate
      mortality and morbidity. Unfortunately, these predisposing risk factors cannot be
      influenced perioperatively. Therefore, therapy should focus on controlling
      perioperative variables that, in combination with the predisposing factors, will
      further exacerbate organ dysfunction. In order to achieve this, more emphasis
      should be given to a patient-specific, goal-directed perfusion approach. This
      review will mainly focus on the impact of perioperative variables.

PMID- 23174918
TI  - Mallampati class does not affect the success rate of intubation through an
      intubating laryngeal mask airway with reverse tracheal tube direction.
AB  - BACKGROUND: The aim of this paper was to assess whether the Mallampati class can
      affect the success rate of intubation through an intubating laryngeal mask airway
      (ILMA) with a reverse conventional tracheal tube direction. METHODS: Two-hundred
      ASA I-II adults, 100 patients with Mallampati class 1 or 2 (MP12) and 100 with
      Mallampati class 3 or 4 (MP34) undergoing elective surgery under general
      anesthesia were enrolled. All the patients were intubated through the ILMA with a
      reverse conventional tracheal tube direction. Tracheal intubation was considered
      successful if proper tracheal positioning was attained within three attempts. Chi
      Square analysis was used to compare categorical variables between the two groups.
      RESULTS: Tracheal intubation was successful in 186 of 200 patients (93.0%): 169
      (84.5%) at the first attempt. Fourteen (7.0%) had to be intubated using direct
      laryngoscope. Both the first attempt success rate and overall success rate were
      similar between the MP12 and MP34 groups (84.0 vs. 85.0%, P=0.845 and 93.0 vs.
      93.0%, respectively). CONCLUSION: Tracheal intubation was successful in 93.0% of
      patients through an ILMA with a reverse conventional tracheal tube. Mallampati
      class did not affect the success rate of intubation.

PMID- 23174920
TI  - Use of positive end-expiratory pressure (PEEP) after elective coronary artery
      bypass grafting (CABG): will duration of PEEP make a difference?

PMID- 23174919
TI  - Gaze-controlled, computer-assisted communication in Intensive Care Unit:
      "speaking through the eyes".
AB  - BACKGROUND: The aim of this study was to test the hypothesis that a gaze
      controlled communication system (eye tracker, ET) can improve communication
      processes between completely dysarthric ICU patients and the hospital staff, in
      three main domains: 1) basic communication processes (i.e., fundamental needs,
      desire, and wishes); 2) the ability of the medical staff to understand the
      clinical condition of the patient; and 3) the level of frustration experienced by
      patient, nurses and physicians. METHODS: Fifteen fully conscious medical and
      surgical patients, 8 physicians, and 15 nurses were included in the study. The
      experimental procedure was composed by three phases: in phase 1 all groups
      completed the preintervention questionnaire; in phase 2 the ET was introduced and
      tested as a communication device; in phase 3 all groups completed the
      postintervention questionnaire. RESULTS: Patients preintervention questionnaires
      showed remarkable communication deficits, without any group effect. Answers of
      physicians and nurses were pretty much similar to the one of patients.
      Postintervention questionnaires showed in all groups a remarkable and
      statistically significant improvement in different communication domains, as well
      as a remarkable decrease of anxiety and disphoric thought. Improvement was also
      reported by physicians and nurses in their ability to understand patient's
      clinical conditions. CONCLUSION: Our results show an improvement in the quality
      of the examined parameters. Better communication processes seem also to lead to
      improvements in several psychological parameters, namely anxiety and drop-out
      depression perceived by both patients and medical staff. Further controlled
      studies are needed to define the ET role in ICU.

PMID- 23174921
TI  - Causes of cardiac troponin elevation in critically ill children.

PMID- 23174922
TI  - An updated meta-analysis to understand the variable efficacy of drotrecogin alfa
      (activated) in severe sepsis and septic shock.
AB  - BACKGROUND: Significant debate continues over the efficacy of drotrecogin alpha
      activated (DAA) in sepsis. This updated meta-analysis provides an updated summary
      effect estimate and explores the reasons for outcome heterogeneity in placebo
      controlled randomized clinical trials of DAA on 28-day all-cause mortality in
      patients with severe sepsis or septic shock. METHODS: Computer searches of
      MEDLINE, EMBASE, the Cochrane Library, ClinicalTrials.gov, published abstracts
      from major intensive care meetings and examination of reference lists were used
      to identify five placebo-controlled randomized clinical trials with 7260
      patients. The primary endpoint was 28-day all-cause mortality. Secondary outcomes
      were 28-day incidence of severe bleeding and intracranial hemorrhage. RESULTS:
      DAA was not associated with improved 28-day all-cause mortality in patients with
      severe sepsis or septic shock (pooled relative risk (RR) of 0.97 [95% CI 0.83
      1.14]), and is associated with an increase in serious bleeding. The significant
      heterogeneity in the pooled RR for 28-day mortality (I2 value of 59.4%, chi2 P
      value 0.043) is no longer present with exclusion of the post-study amendment
      portion of PROWESS (I2 value of 0%, chi2 P-value 0.44 without PROWESS post
      amendment). Using meta-regression, the best ranked predictor of outcome
      heterogeneity was baseline mortality in the placebo arm, which was among the
      highest in PROWESS. CONCLUSION: DAA is not associated with improved survival in
      patients with severe sepsis or septic shock. Further studies should be done to
      determine whether changes in supportive therapy for sepsis explain the variable
      efficacy of DAA in randomized controlled clinical trials observed over time.

PMID- 23174923
TI  - Tracheostomy in Intensive Care Unit: a national survey in Italy.
AB  - BACKGROUND: The aim of the present study was to evaluate the frequency of
      different techniques, indications, timing, as well as procedural features,
      sedation and ventilation protocols, early and late complications of tracheostomy
      in Intensive Care Unit (ICU). METHODS: This was a retrospective survey on data
      collected in 2011. A questionnaire was mailed to all members of the Italian
      Society of Anesthesia, Analgesia and Intensive Care (SIAARTI). RESULTS: We
      included in the analysis 131 questionnaires. We found that: 1) Ciaglia Blue
      Rhino(r) (CBR) was the most commonly used tracheostomy (32.8%; N.=1953) and the
      main indication was prolonged mechanical ventilation (58.8%; N.=77); 2)
      tracheostomy was performed between 7-15 days (71.8%; N.=94) from ICU admission by
      a dedicated team (62.6%; N.=82) involving more than one intensive care physician
      and a nurse; 3) tracheostomy was frequently guided by fiberoptic bronchoscope
      (93.1%, N.=122) while neck ultrasounds were used as a screening procedure to
      assess at-risk structure often in presence of pathological anatomical structures
      (68.7%; N.=90); 4) ventilation protocol and sedation-analgesia-neuromuscular
      blocking protocol were available in 83.2% and 58.8% of ICUs, respectively; 5)
      minor bleeding controlled by compression was the most common early and late
      complication. CONCLUSION: Percutaneous tracheostomy is well established in
      Italian ICUs and CBR is the most popular technique performed in patients
      requiring prolonged mechanical ventilation. Tracheostomy is usually performed by
      a dedicated team using a specific sedation-analgesia-neuromuscular blocking and
      ventilation protocol, guided by fiberoptic bronchoscope and/or neck ultrasounds.
      Bleeding controlled by compression was the most common early and late
      complication.

PMID- 23174924
TI  - ICU admission of patients with hematological malignancies: the debate continues.

PMID- 23174925
TI  - Author reply on comment on "neuromonitoring in traumatic brain injury".

PMID- 23174926
TI  - Performance of indirect and direct laryngoscopy for endotracheal intubation in
      suspected difficult airways.

PMID- 23174927
TI  - PRES: clinical evidence or incidental finding?

PMID- 23174928
TI  - Airway management in pediatric patients using the Glidescope Cobalt(r): a
      feasibility study. Response to the letter to the editor.

PMID- 23174929
TI  - Kidney biopsies in the ICU: is it worth the risk?

PMID- 23174930
TI  - String mitochondria in mouse soleus muscle.
AB  - Red myofibers in mouse soleus muscle have two spatially distinct populations of
      mitochondria: one where these organelles are disposed in large clusters just
      inside the sarcolemma and the other situated between the myofibrils. In most
      cases, the interfibrillar mitochondria (IFM), which are much smaller than the
      subsarcolemmal ones (SSM), are arranged as pairs, with each member on opposite
      sides of the Z-line. In some myofibers, the IFM have fused end-to-end to form
      greatly elongated organelles, which we call "string mitochondria." Although
      narrow, these can be many sarcomeres in length. The SSM do not form string
      mitochondria. Most of the string mitochondria exhibit many instances of
      "pinching," a process involved in mitochondrial division. Elements of
      sarcoplasmic reticulum are intimately involved with each mitochondrial membrane
      invagination. It appears as if the fusion:fission balance of IFM in the soleus
      muscle is slightly out of kilter, with end-to-end fusion predominating over
      fission.

PMID- 23174931
TI  - Electrochemistry of dithienylethenes and their application in electropolymer
      modified photo- and redox switchable surfaces.
AB  - Diarylethenes have proven to be versatile responsive components in many
      applications due to their photochromic properties. In recent years their
      potential use as redox switchable components has become increasingly apparent.
      Applying dithienylethenes as redox switchable components requires their
      immobilisation on conducting substrates and hence electropolymerisation is a
      promising, albeit, challenging approach to developing such systems. In this
      review the electrochemical properties of dithienylethenes will be discussed
      together with a consideration of mechanistic aspects of the switching processes
      observed followed by a review of recent efforts to develop dithienylethene based
      redox and photoswitchable redox polymers through electropolymerisation.

PMID- 23174932
TI  - SMARCB1 protein and mRNA loss is not caused by promoter and histone
      hypermethylation in epithelioid sarcoma.
AB  - About 10% of epithelioid sarcomas have biallelic mutation of the SMARCB1 (SWI/SNF
      related, matrix-associated, actin-dependent regulator of chromatin, subfamily b,
      member 1) gene resulting in a lack of this nuclear protein. It has been suggested
      that SMARCB1 may be silenced by epigenetic changes in the remaining 90% of
      tumors. Thus, we hypothesized that the promoter of SMARCB1 is hypermethylated. We
      also examined SMARCB1 mRNA level to determine if a post-translational change was
      possible. Thirty-six cases of epithelioid sarcomas were studied.
      Immunohistochemistry and mutation analysis of the SMARCB1 gene were performed to
      select appropriate cases. Methylation status was assessed by methylation-specific
      PCR. Laser capture microdissection of tumor cells followed by real-time PCR was
      applied to examine the expression of SMARCB1 mRNA. Of 36 epithelioid sarcomas, 31
      (86%) displayed a lack of SMARCB1 nuclear protein. In all, 4 (13%) of 31 SMARCB1
      negative cases harbored biallelic deletion while 9 (33%) cases showed single
      allelic deletion. One (4%) frameshift deletion of exon 3 and one point mutation
      of exon 7 were also found. In 16 (59%) cases, both alleles were intact.
      Altogether, 25/31 (81%) SMARCB1-negative cases had at least one intact allele.
      None of these cases demonstrated promoter hypermethylation. Low levels of SMARCB1
      mRNA were found in all cases with tumor tissue extracted RNA (because of the
      minimal normal cell contamination) but no mRNA could be detected in laser
      dissected cases (containing only tumor cells). Enhancer of zeste homolog 2 (EZH2)
      overexpression was not characteristic of epithelioid sarcoma. Thus, loss of
      SMARCB1 expression in epithelioid sarcoma is caused neither by DNA
      hypermethylation nor by post-translational modifications. Most likely it is the
      microRNA destruction of SMARCB1 mRNA but further investigations are needed to
      elucidate this issue.

PMID- 23174933
TI  - Non-mammary metastases to the breast and axilla: a study of 85 cases.
AB  - Non-mammary metastases to the breast and axilla are rare occurrences. However,
      they are important diagnostic considerations as their treatment and prognosis
      differ significantly from primary breast cancer. Between 1990 and 2010, we
      identified a total of 85 patients, 72 women and 13 men, with non-mammary
      malignancies involving the breast, axilla, or both. The tumor types consisted of
      carcinoma (58%), melanoma (22%) and sarcoma (20%). Ovary was the most common site
      of origin for carcinoma, and metastatic high-grade ovarian serous carcinoma was
      most frequently misdiagnosed as a primary breast carcinoma. Melanoma was the
      single most common non-carcinomatous tumor type to involve the breast and/or
      axilla, and uterine leiomyosarcoma was the most common type of sarcoma. Most
      patients (77%) had other metastases at the time of diagnosis of the tumor, but in
      11% the breast or axillary lesion was the first presentation. Without a clinical
      history, non-mammary metastases were difficult to diagnose because the majority
      of cases presented with a solitary nodule and lacked pathognomonic pathologic
      features. There were, however, certain recurrent histological findings
      identified, such as the often relatively well-circumscribed growth pattern of the
      metastatic lesion surrounded by a fibrous pseudocapsule, and the absence of an in
      situ carcinoma. Overall, these patients had poor survival; 96% of patients with
      follow-up available are dead of disease, with a median survival of 15 months
      after the diagnosis of the breast or axillary lesion. This finding emphasizes the
      need to accurately identify these tumors as metastases in order to avoid
      unnecessary procedures and treatments in these patients.

PMID- 23174934
TI  - Transgelin is a novel marker of smooth muscle differentiation that improves
      diagnostic accuracy of leiomyosarcomas: a comparative immunohistochemical
      reappraisal of myogenic markers in 900 soft tissue tumors.
AB  - Immunohistochemical use of myogenic markers serves to define smooth or skeletal
      muscle differentiation in soft tissue tumors. Establishing smooth muscle
      differentiation in malignant lesions can be challenging in some cases. We
      immunohistochemically examined 900 soft tissue tumors selected from the French
      Sarcoma Group's archived tissue collection, which contains a large number of
      leiomyosarcomas. The four most widely used smooth muscle diagnostic markers were
      evaluated (smooth muscle actin, desmin, h-caldesmon and calponin), and compared
      with a novel marker, transgelin. The diagnostic performance of each marker was
      statistically assessed in terms of sensitivity (Se), specificity (Sp), positive
      predictive value (PPV), negative predictive value (NPV) and accuracy (A), in
      leiomyosarcomas versus all other sarcomas including gastrointestinal stromal
      tumors (GIST), and second in leiomyosarcomas versus specific tumor types. In
      leiomyosarcomas versus all other sarcomas including GIST, transgelin emerged as
      the best diagnostic marker (Se: 83%, Sp: 82%, PPV: 67%, NPV: 92%, A: 83%),
      compared with smooth muscle actin (Se: 75%, Sp: 83, PPV: 66%, NPV: 89%, A: 81%),
      desmin (Se: 45%, Sp: 88%, PPV: 62%, NPV: 79%, A: 75%), h-caldesmon (Se: 50%, Sp:
      90%, PPV: 67%, NPV: 81%, A: 78%) and calponin (Se: 76%, Sp: 70, PPV: 52%, NPV:
      87%, A: 71%). In leiomyosarcomas compared with other specific tumor types such as
      undifferentiated pleomorphic sarcoma and myxofibrosarcoma, the accuracy for
      transgelin varied from 80 to 87% whereas it was lower for all other markers
      (between 51 and 80%). These results indicate that transgelin could be used in
      practice as an additional marker useful for decision making, especially in those
      tumors with incomplete immunophenotypes.

PMID- 23174935
TI  - Clinicopathologic analysis of IgG4-related skin disease.
AB  - IgG4-related disease is a recently recognized systemic syndrome characterized by
      mass-forming lesions with lymphoplasmacytic infiltration, increase in the number
      of IgG4(+) cells in affected tissues and elevation of serum IgG4 levels. In 2009,
      we were the first to report skin lesions in patients with IgG4-related disease,
      but no large case series has been reported and clinicopathological findings
      remain unclear. To clarify these features, we herein report 10 patients (9 men
      and 1 woman; median age, 64 years; age range, 46-81 years) with IgG4-related skin
      disease. All patients had erythematous and itchy plaques or subcutaneous nodules
      on the skin of the head and neck, particularly in the periauricular, cheek, and
      mandible regions, except for one patient, whose forearm and waist skin were
      affected. In addition, eight patients had extracutaneous lesions: these were
      found on the lymph nodes in six patients, the lacrimal glands in three patients,
      the parotid glands in three patients, and the kidney in one patient.
      Histologically examined extracutaneous lesions were consistent with IgG4-related
      disease; five of six lymph node lesions showed progressively transformed germinal
      centers-type IgG4-related lymphadenopathy. Cases of IgG4-related skin disease
      were classified into two histological patterns: those exhibiting a nodular
      dermatitis pattern and those with a subcutaneous nodule pattern. The infiltrate
      was rich in plasma cells, small lymphocytes, and eosinophils; the majority of the
      plasma cells were IgG4(+). The IgG4(+) cell count was 49-396 per high-power field
      (mean+/-s.d., 172+/-129), with an IgG4(+)/IgG(+) cell ratio ranging from 62 to
      92%. Serum IgG4 levels were elevated in all examined patients. In conclusion,
      patients with IgG4-related skin disease had uniform clinicopathology. Lesions
      were frequently present on the skin of the periauricular, cheek, and mandible
      regions, and were frequently accompanied by IgG4-related lymphadenopathy.

PMID- 23174936
TI  - Proliferation indices of phosphohistone H3 and Ki67: strong prognostic markers in
      a consecutive cohort with stage I/II melanoma.
AB  - Cellular proliferation is correlated with the progression of melanoma.
      Accordingly, the proliferation index of H&E-stained thin melanomas was recently
      included in the staging system of the American Joint Committee on Cancer. Yet,
      the immunohistochemical markers of proliferation phosphohistone H3 and Ki67 may
      improve such indices. To accurately quantify these markers, they should be
      combined with a melanocytic marker, for example, MART1 in an immunohistochemical
      double stain; also enabling automated quantification by image analysis. The aim
      of the study was to compare the prognostic impact of phosphohistone H3/MART1,
      Ki67/MART1, and H&E stains in primary cutaneous melanoma, and to determine the
      difference between indices established in hot spots and the global tumor areas.
      The study included 153 consecutive stage I/II melanoma-patients. The follow-up
      time was 8-14 years for event-free melanoma. Recurrent disease occurred in 43
      patients; 37 died of melanoma. Both events occurred in only three thin melanomas.
      Their paraffin-embedded tissue was stained for phosphohistone H3/MART1,
      Ki67/MART1, and with H&E. And proliferation indices were established in 1-mm(2)
      hot spots and in the global tumor areas. In multivariate Cox analyses, only hot
      spot indices of phosphohistone H3/MART1 and Ki67/MART1 were independent
      prognostic markers. Phosphohistone H3/MART1 tended to be better than Ki67/MART1
      with adjusted hazard ratios of 3.66 (95% CI, 1.40-9.55; P=0.008) for progression
      free survival and 3.42 (95% CI, 1.29-9.04; P=0.013) for melanoma-specific death.
      In all stains, prognostic performance was substantially improved by using hot
      spots instead of the global tumor areas. In conclusion, phosphohistone H3/MART1
      and Ki67/MART1 were superior to H&E stains, and hot spots superior to the global
      tumor areas. Given the potential for automated analysis, these double stains seem
      to be robust alternatives to conventional mitotic detection by H&E in stage I/II
      melanomas in general. This was particularly true for thick melanomas whereas no
      specific analyses for thin melanomas only could be performed.

PMID- 23174938
TI  - Pathological study of archival lung tissues from five fatal cases of avian H5N1
      influenza in Vietnam.
AB  - Highly pathogenic avian H5N1 influenza virus (H5N1) infection in humans causes
      acute respiratory distress syndrome, leading to multiple organ failure. Five
      fatal cases of H5N1 infection in Vietnam were analyzed pathologically to reveal
      virus distribution, and local proinflammatory cytokine and chemokine expression
      profiles in formalin-fixed, paraffin-embedded lung tissues. Our main
      histopathological findings showed diffuse alveolar damage in the lungs. The
      infiltration of myeloperoxidase-positive and/or CD68 (clone KP-1)-positive
      neutrophils and monocytes/macrophages was remarkable in the alveolar septa and
      alveolar spaces. Immunohistochemistry revealed that H5N1 mainly infected alveolar
      epithelial cells and monocytes/macrophages in lungs. H5N1 replication was
      confirmed by detecting H5N1 mRNA in epithelial cells using in situ hybridization.
      Quantitation of H5N1 RNA using quantitative reverse transcription PCR assays
      revealed that the level of H5N1 RNA was increased in cases during early phases of
      the disease. We quantified the expression of tumor necrosis factor-alpha (TNF
      alpha), interleukin (IL)-6, IL-8, regulated on activation normal T-cell expressed
      and secreted (commonly known as RANTES), and interferon-gamma-inducible protein
      of 10 kDa (IP-10) in formalin-fixed, paraffin-embedded lung sections. Their
      expression levels correlated with H5N1 RNA copy numbers detected in the same lung
      region. Double immunofluorescence staining revealed that TNF-alpha, IL-6, IL-8
      and IP-10 were expressed in epithelial cells and/or monocytes/macrophages. In
      particular, IL-6 was also expressed in endothelial cells. The dissemination of
      H5N1 beyond respiratory organs was not confirmed in two cases examined in this
      study.

PMID- 23174937
TI  - Frequency of mutations and polymorphisms in borderline ovarian tumors of known
      cancer genes.
AB  - Borderline ovarian tumors represent an understudied subset of ovarian tumors.
      Most studies investigating aberrations in borderline tumors have focused on
      KRAS/BRAF mutations. In this study, we conducted an extensive analysis of
      mutations and single-nucleotide polymorphisms (SNPs) in borderline ovarian
      tumors. Using the Sequenom MassArray platform, we investigated 160
      mutations/polymorphisms in 33 genes involved in cell signaling, apoptosis,
      angiogenesis, cell cycle regulation and cellular senescence. Of 52 tumors
      analyzed, 33 were serous, 18 mucinous and 1 endometrioid. KRAS c.35G>A p.Gly12Asp
      mutations were detected in eight tumors (six serous and two mucinous), BRAF V600E
      mutations in two serous tumors, and PIK3CA H1047Y and PIK3CA E542K mutations in a
      serous and an endometrioid BOT, respectively. CTNNB1 mutation was detected in a
      serous tumor. Potentially functional polymorphisms were found in vascular
      endothelial growth factor (VEGF), ABCB1, FGFR2 and PHLPP2. VEGF polymorphisms
      were the most common and detected at four loci. PHLPP2 polymorphisms were more
      frequent in mucinous as compared with serous tumors (P=0.04), with allelic
      imbalance in one case. This study represents the largest and most comprehensive
      analysis of mutations and functional SNPs in borderline ovarian tumors to date.
      At least 25% of borderline ovarian tumors harbor somatic mutations associated
      with potential response to targeted therapeutics.

PMID- 23174939
TI  - SDHA mutations in adult and pediatric wild-type gastrointestinal stromal tumors.
AB  - Most gastrointestinal stromal tumors (GISTs) harbor oncogenic mutations in KIT or
      platelet-derived growth factor receptor-alpha. However, a small subset of GISTs
      lacks such mutations and is termed 'wild-type GISTs'. Germline mutation in any of
      the subunits of succinate dehydrogenase (SDH) predisposes individuals to
      hereditary paragangliomas and pheochromocytomas. However, germline mutations of
      the genes encoding SDH subunits A, B, C or D (SDHA, SDHB, SDHC or SDHD;
      collectively SDHx) are also identified in GISTs. SDHA and SDHB
      immunohistochemistry are reliable techniques to identify pheochromocytomas and
      paragangliomas with mutations in SDHA, SDHB, SDHC and SDHD. In this study, we
      investigated if SDHA immunohistochemistry could also identify SDHA-mutated GISTs.
      Twenty-four adult wild-type GISTs and nine pediatric/adolescent wild-type GISTs
      were analyzed with SDHB, and where this was negative, then with SDHA
      immunohistochemistry. If SDHA immunohistochemistry was negative, sequencing
      analysis of the entire SDHA coding sequence was performed. All nine
      pediatric/adolescent GISTs and seven adult wild-type GISTs were negative for SDHB
      immunohistochemistry. One pediatric GIST and three SDHB-immunonegative adult wild
      type GISTs were negative for SDHA immunohistochemistry. In all four SDHA-negative
      GISTs, a germline SDHA c.91C>T transition was found leading to a nonsense
      p.Arg31X mutation. Our results demonstrate that SDHA immunohistochemistry on
      GISTs can identify the presence of an SDHA germline mutation. Identifying GISTs
      with deficient SDH activity warrants additional genetic testing, evaluation and
      follow-up for inherited disorders and paragangliomas.

PMID- 23174940
TI  - Improving SAR estimations in MRI using subject-specific models.
AB  - To monitor and strategically control energy deposition in magnetic resonance
      imaging (MRI), measured as a specific absorption rate (SAR), numerical methods
      using generic human models have been employed to estimate worst-case values.
      Radiofrequency (RF) sequences are therefore often designed conservatively with
      large safety margins, potentially hindering the full potential of high-field
      systems. To more accurately predict the patient SAR values, we propose the use of
      image registration techniques, in conjunction with high-resolution image and
      tissue libraries, to create patient-specific voxel models. To test this, a
      matching model from the archives was first selected. Its tissue information was
      then warped to the patient's coordinates by registering the high-resolution
      library image to the pilot scan of the patient. Results from studying the models'
      1 g SAR distribution suggest that the developed patient model can predict regions
      of elevated SAR within the patient with remarkable accuracy. Additionally, this
      work also proposes a voxel analytical metric that can assist in the construction
      of a patient library and the selection of the matching model from the library for
      a patient. It is hoped that, by developing voxel models with high accuracy in
      patient-specific anatomy and positioning, the proposed method can accurately
      predict the safety margins for high-field human applications and, therefore
      maximize the safe use of RF sequence power in high-field MRI systems.

PMID- 23174941
TI  - Yttrium 90 radioembolization: the horizon is changing for patients with
      intermediate and advanced hepatocellular carcinoma.

PMID- 23174944
TI  - Genetic modifier to chromatin may contribute to 22q11 deletion/VCF/DiGeorge
      syndrome variability: MOZ gene may also exacerbate effects of retinoic acid in
      genetic disorder.

PMID- 23174945
TI  - Newborn screening for Duchenne muscular dystrophy gains support: researchers to
      push for federal recommendation to have states add DMD test to newborn panel.

PMID- 23174947
TI  - Broken rice kernels and the kinetics of rice hydration and texture during
      cooking.
AB  - BACKGROUND: During rice milling and processing, broken kernels are inevitably
      present, although to date it has been unclear as to how the presence of broken
      kernels affects rice hydration and cooked rice texture. Therefore, this work
      intended to study the effect of broken kernels in a rice sample on rice hydration
      and texture during cooking. Two medium-grain and two long-grain rice cultivars
      were harvested, dried and milled, and the broken kernels were separated from
      unbroken kernels. Broken rice kernels were subsequently combined with unbroken
      rice kernels forming treatments of 0, 40, 150, 350 or 1000 g kg(-1) broken
      kernels ratio. Rice samples were then cooked and the moisture content of the
      cooked rice, the moisture uptake rate, and rice hardness and stickiness were
      measured. RESULTS: As the amount of broken rice kernels increased, rice sample
      texture became increasingly softer (P < 0.05) but the unbroken kernels became
      significantly harder. Moisture content and moisture uptake rate were positively
      correlated, and cooked rice hardness was negatively correlated to the percentage
      of broken kernels in rice samples. CONCLUSION: Differences in the proportions of
      broken rice in a milled rice sample play a major role in determining the texture
      properties of cooked rice. Variations in the moisture migration kinetics between
      broken and unbroken kernels caused faster hydration of the cores of broken rice
      kernels, with greater starch leach-out during cooking affecting the texture of
      the cooked rice. The texture of cooked rice can be controlled, to some extent, by
      varying the proportion of broken kernels in milled rice.

PMID- 23174948
TI  - Microtubule inhibition causes epidermal growth factor receptor inactivation in
      oesophageal cancer cells.
AB  - Drugs that interfere with microtubule function can prevent cells from mitosis and
      may cause cell cycle arrest or apoptosis. Various microtubule targeting agents,
      both stabilizers and inhibitors, are used in a clinical setting to treat cancer.
      In the current study, we investigated the sensitivity of oesophageal cancer cells
      to different microtubule targeting agents. The current study demonstrated that
      different microtubule targeting agents disrupted the microtubule network and
      inhibited survival of oesophageal cancer cells in a dose-dependent manner.
      Interestingly, an additional cellular effect with inhibition of tyrosine
      phosphorylation of the EGFR and subsequent downregulation of EGFR-induced
      signalling was also observed, suggesting an additional mechanism of action for
      microtubule destabilising agents. A tyrosine phosphatase inhibitor, sodium
      orthovanadate, could reverse the EGFR dephosphorylation effects induced by
      microtubule targeting agents. The EGFR dephosphorylation could be reversed by a
      tyrosine phosphatase inhibitor, indicating that disruption of the microtubule
      network may lead to activation of a protein tyrosine phosphatase (PTP) that can
      regulate EGFR phosphorylation and activation, an effect of potential clinical
      relevance for combination therapies in patients.

PMID- 23174949
TI  - Imaging of biological tissues with pixel-level analysis of second-order
      susceptibility.
AB  - We discuss the recent advances in the development and applications of second
      order susceptibility as a contrast mechanism in optical microscopy for biological
      tissues. We review nonlinear optical methods and approaches for differentiation
      of tissue structures and discrimination of normal and pathological skin tissues,
      which have been demonstrated for the potential use in clinical diagnosis. In
      addition, the potential of second-order susceptibility imaging, encompassing
      applications in differentiating various types of collagen molecules for clinical
      diagnosis, is demonstrated. Finally, we discuss future development and
      application of this technique.

PMID- 23174950
TI  - Study of molecule variations in renal tumor based on confocal micro-Raman
      spectroscopy.
AB  - Confocal micro-Raman spectroscopy--a valuable analytical tool in biological and
      medical field of research-allows probing molecular vibrations of samples without
      external labels or extensive preparation. We employ confocal micro-Raman
      spectroscopy to characterize renal tumors and normal tissue. Results show that
      Raman peaks of the renal tumor at 788 and 1087  cm-1, which belong to
      (nu)(s)PO(2)- and (nu)(as)PO(2)- stretching, respectively, have an obvious
      increase. At the same time, the ratio of I855/I831 in renal tumor tissue is 1.39
      +/- 0.08, while that in normal renal tissue is 2.44 +/- 0.05 (p < 0.01). This
      means that more tyrosine conformation transform from "buried" to "exposed" in the
      presence of cancer. Principal component analysis is used to classify the Raman
      spectra of renal tumor tissue and normal tissue.

PMID- 23174951
TI  - Analysis of collagen fiber domain organization by Fourier second harmonic
      generation microscopy.
AB  - We present an automated and systematic two-dimensional discrete Fourier transform
      (2D-FFT) approach to analyze collagen fiber organization through the use of
      second harmonic generation (SHG) microscopy. Average orientations of individual
      domains and Ising-like order parameters introduced to characterize the
      correlation between orientations of adjacent domains may be used to
      quantitatively characterize fibrous tissues. Our approach was applied to analyze
      tissues including rat tail tendon, mouse skin, bovine corneas, and human corneas.
      We also show that collagen fiber organization in normal and keratokonus human
      corneas may be distinguished. The current approach may be used for the
      quantitative differentiation of SHG collagen fiber morphology in different
      tissues and may be applied for diagnostic purposes.

PMID- 23174954
TI  - Pyridone fused boron-dipyrromethenes: synthesis and properties.
AB  - In this paper a general procedure for the introduction of pyridone moiety was
      developed, using a Friedlander reaction, for post-modification of ready-made
      BODIPY core, from which three pyridone-fused BODIPYs 1, 2 and 3 were generated.
      This method is complementary to the classical method for obtaining aromatic ring
      fused BODIPYs, which begins with the condensation of the corresponding aromatic
      ring-fused pyrroles. These pyridone-fused BODIPYs are distinctive, possessing
      favorable photophysical characteristics with strong absorption, high bright
      orange fluorescence and easy reduction due to the electron-withdrawing effect of
      the fused pyridone moiety. More important, these BODIPYs bear reactive functions
      which are applicable in proteins labeling by bioorthogonal chemical reactions.

PMID- 23174953
TI  - Expression of urokinase plasminogen activator and plasminogen activator inhibitor
      type-1 in ovarian cancer and its clinical significance.
AB  - The urokinase plasminogen activator system, which consists of urokinase
      plasminogen activator (uPA), plasminogen activator inhibitor type-1 (PAI-1) and
      urokinase plasminogen activator receptor (uPAR), plays an important role in tumor
      invasion and metastasis, and it may be a potential diagnostic biomarker and
      therapeutic target in cancer. It has been found that the expression of uPA and
      PAI-1 in ovarian cancer is related to clinical pathologies, while their effects
      on the biological behavior of tumor cells and their clinical significance are
      still unknown. In this study, 100 tissue samples (60 samples from malignant
      tumors, 20 from benign tumors and 20 from controls) and 147 blood samples (49
      samples each from patients with malignant tumors, benign tumors and control
      group, respectively) were analyzed. The positive expression levels of uPA and PAI
      1 in the malignant tumor samples and their serum concentrations in the malignant
      group were all significantly higher than these levels in the benign tumors and
      controls. In addition, the levels in patients with poorly differentiated and
      stage III-IV cancers, cancers with metastases as well as residual tumors >2 cm
      after surgery, were all obviously increased, consistent with their concentrations
      in serum. The Cox model analysis showed that expression of uPA at the
      transcription level had significant associations with prognosis. In addition, uPA
      greatly enhanced the abilities of cell invasion, migration and adhesion through
      its overexpression in SKOV3 cells. Collectively, our results showed that uPA and
      PAI-1 play important roles in ovarian cancer development; therefore, their
      expression in tissues and their concentrations in serum would greatly assist the
      diagnosis and prediction of the prognosis in ovarian cancer.

PMID- 23174952
TI  - Macrophage migration inhibitory factor contributes to ethanol-induced liver
      injury by mediating cell injury, steatohepatitis, and steatosis.
AB  - Macrophage migration inhibitory factor (MIF), a multipotent protein that exhibits
      both cytokine and chemotactic properties, is expressed by many cell types,
      including hepatocytes and nonparenchymal cells. We hypothesized that MIF is a key
      contributor to liver injury after ethanol exposure. Female C57BL/6 or MIF-/- mice
      were fed an ethanol-containing liquid diet or pair-fed control diet for 4 (11%
      total kcal;early response) or 25 (32% kcal; chronic response) days. Expression of
      MIF messenger RNA (mRNA) was induced at both 4 days and 25 days of ethanol
      feeding. After chronic ethanol, hepatic triglycerides and plasma alanine
      aminotransferase (ALT) and aspartate aminotransferase (AST) were increased in
      wildtype, but not MIF-/-, mice. In order to understand the role of MIF in chronic
      ethanol-induced liver injury, we investigated the early response of wildtype and
      MIF-/- to ethanol. Ethanol feeding for 4 days increased apoptosis of hepatic
      macrophages and activated complement in both wildtype and MIF-/- mice. However,
      tumor necrosis factor alpha (TNF-alpha) expression was increased only in wildtype
      mice. This attenuation of TNF-alpha expression was associated with fewer F4/80+
      macrophages in liver of MIF-/- mice. After 25 days of ethanol feeding, chemokine
      expression was increased in wildtype mice, but not MIF-/- mice. Again, this
      protection was associated with decreased F4/80+ cells in MIF-/- mice after
      ethanol feeding. Chronic ethanol feeding also sensitized wildtype, but not MIF-/
      , mice to lipopolysaccharide, increasing chemokine expression and monocyte
      recruitment into the liver. CONCLUSION: Taken together, these data indicate that
      MIF is an important mediator in the regulation of chemokine production and immune
      cell infiltration in the liver during ethanol feeding and promotes ethanol
      induced steatosis and hepatocyte damage.

PMID- 23174955
TI  - In vitro evaluation of the L-peptide modified magnetic lipid nanoparticles as
      targeted magnetic resonance imaging contrast agent for the nasopharyngeal cancer.
AB  - The purpose of this study was to analyze the encapsulation of superparamagnetic
      iron oxide nanoparticles (SPION) by the lipid nanoparticle conjugated with the 12
      mer peptides (RLLDTNRPLLPY, L-peptide), and the delivery of this complex into
      living cells. The lipid nanoparticles employed in this work were highly
      hydrophilic, stable, and contained poly(ethylene-glycol) for conjugation to the
      bioactive L-peptide. The particle sizes of two different magnetic lipid
      nanoparticles, L-peptide modified (LML) and non-L-peptide modified (ML), were
      both around 170 nm with a narrow range of size disparity. The transversal
      relaxivity, r2, for both LML and ML nanoparticles were found to be significantly
      higher than the longitudinal relaxivity r1 (r2/r1 > 20). The in vitro tumor cell
      targeting efficacy of the LML nanoparticles were evaluated and compared to the ML
      nanoparticles, upon observing cellular uptake of magnetic lipid nanoparticles by
      the nasopharyngeal carcinoma cells, which express cell surface specific protein
      for the L-peptide binding revealed. In the Prussian blue staining experiment,
      cells incubated with LML nanoparticles indicated much higher intracellular iron
      density than cells incubated with only the ML and SPION nanoparticles. In
      addition, the MTT assay showed the negligible cell cytotoxicity for LML, ML and
      SPION nanoparticles. The MR imaging studies demonstrate the better T2-weighted
      images for the LML-nanoparticle-loaded nasopharyngeal carcinoma cells than the ML
      and SPION-loaded cells.

PMID- 23174958
TI  - Reply to letter to the editor: concerns about standards of reporting clinical
      trials: an RCT comparing the Bobath concept and motor relearning interventions
      for rehabilitation of stroke patients as an exemplar.

PMID- 23174956
TI  - Curcumin alleviates oxidative stress, inflammation, and renal fibrosis in remnant
      kidney through the Nrf2-keap1 pathway.
AB  - SCOPE: We hypothesized that curcumin, by increasing the expression of nuclear
      factor-erythroid-2-related factor 2 (Nrf2), could reduce oxidative stress,
      inflammation, and renal fibrosis in remnant kidney. METHODS AND RESULTS: Sprague
      Dawley rats were subjected to 5/6 nephrectomy and randomly assigned to untreated
      (Nx), curcumin-treated (75 mg/kg/day, orally), and telmisartan-treated groups (10
      mg/kg/day, orally; as positive control). Sham-operated rats also served as
      controls. Five/sixth nephrectomy caused renal dysfunction, as evidenced by
      elevated proteinuria, blood urea nitrogen, and plasma creatinine, and decreased
      creatinine clearance that were ameliorated by curcumin or telmisartan treatment.
      The Nx rats demonstrated reduced Nrf2 protein expression, whereas the Kelch-like
      ECH-associated protein 1 was upregulated and heme oxygenase-1 level was
      significantly diminished. Consequently, Nx animals had significantly higher
      kidney malondialdehyde concentration and lower glutathione peroxidase activity,
      which was associated with the upregulation of nicotinamide adenine dinucleotide
      phosphatase oxidase subunit (p67(phox) and p22(phox) ), NF-kappaB p65, TNF-alpha,
      TGF-beta1, cyclooxygenase-2, and fibronectin accumulation in remnant kidney.
      Interestingly, all of these changes were ameliorated by curcumin or telmisartan.
      CONCLUSION: These findings demonstrate that, by modulating Nrf2-Keap1 pathway,
      the curcumin effectively attenuates oxidative stress, inflammation, and renal
      fibrosis, which suggest that curcumin hold promising potential for safe treatment
      of chronic kidney disease.

PMID- 23174959
TI  - An aggregation-induced emission luminophore with multi-stimuli single- and two
      photon fluorescence switching and large two-photon absorption cross section.
AB  - A novel aggregation- and crystallization-induced emission luminophore (ENPOMe)
      containing tetraphenylethene and acrylonitrile moieties with high fluorescence
      efficiency (Phi(F) of up to 0.85) has been easily synthesized. ENPOMe has an
      exceptionally large two-photon absorption cross section (sigma) of 5548 GM, and
      exhibits striking multi-stimuli-responsive single- and two-photon fluorescence
      switching with excellent reversibility in the solid state.

PMID- 23174960
TI  - Take aim.

PMID- 23174961
TI  - Naming names.

PMID- 23174962
TI  - Free at last!

PMID- 23174970
TI  - Lithium-air batteries: Something from nothing.

PMID- 23174971
TI  - Site-selective reactions: Remodelling by diversity and design.

PMID- 23174972
TI  - Water splitting: Catalyst or spectator?

PMID- 23174973
TI  - Single-molecule magnets: Uranyl steps in the ring.

PMID- 23174974
TI  - Organic photochemistry: Exciting excited-state aromaticity.

PMID- 23174975
TI  - Anticancer agents: Unleash the forces within.

PMID- 23174977
TI  - Inelastic scattering of hydroxyl radicals with helium and argon by velocity-map
      imaging.
AB  - The hydroxyl radical (OH) is one of the most interesting molecules in molecular
      dynamics. In particular, inelastic collisions of free radicals such as OH are
      profoundly important in environments ranging from combustion to astrochemistry.
      However, measuring the velocities of OH molecules in specific internal quantum
      states has proven to be very difficult. A method that can provide this important
      information is velocity-map imaging. Although this technique is very widely
      applicable in principle, it does require a sensitive and selective laser
      ionization scheme. Here we show that, under the right conditions, velocity-map
      imaging can be applied to the study of the inelastic scattering of OH using
      crossed-molecular-beam methods. We measure fully quantum-state-specified product
      angular distributions for OH collisions with helium and argon. The agreement
      between exact close-coupling quantum scattering calculations on ab initio
      potential energy surfaces and experimental data is generally very satisfactory,
      except for scattering in the most forward directions.

PMID- 23174976
TI  - Reaction-based small-molecule fluorescent probes for chemoselective bioimaging.
AB  - The dynamic chemical diversity of elements, ions and molecules that form the
      basis of life offers both a challenge and an opportunity for study. Small
      molecule fluorescent probes can make use of selective, bioorthogonal chemistries
      to report on specific analytes in cells and in more complex biological specimens.
      These probes offer powerful reagents to interrogate the physiology and pathology
      of reactive chemical species in their native environments with minimal
      perturbation to living systems. This Review presents a survey of tools and
      tactics for using such probes to detect biologically important chemical analytes.
      We highlight design criteria for effective chemical tools for use in biological
      applications as well as gaps for future exploration.

PMID- 23174978
TI  - Combinatorial evolution of site- and enantioselective catalysts for polyene
      epoxidation.
AB  - Selectivity in the catalytic functionalization of complex molecules is a major
      challenge in chemical synthesis. The problem is magnified when there are several
      possible stereochemical outcomes and when similar functional groups occur
      repeatedly within the same molecule. Selective polyene oxidation provides an
      archetypical example of this challenge. Historically, enzymatic catalysis has
      provided the only precedents. Although non-enzymatic catalysts that meet some of
      these challenges became known, a comprehensive solution has remained elusive.
      Here, we describe low molecular weight peptide-based catalysts, discovered
      through a combinatorial synthesis and screening protocol, that exhibit site- and
      enantioselective oxidation of certain positions of various isoprenols. This
      diversity-based approach, which exhibits features reminiscent of the directed
      evolution of enzymes, delivers catalysts that compare favourably to the state-of
      the-art for the asymmetric oxidation of these compounds. Moreover, the approach
      culminated in catalysts that exhibit alternative-site selectivity in comparison
      to oxidation catalysts previously described.

PMID- 23174979
TI  - Electronic tuning of site-selectivity.
AB  - Site-selective functionalizations of complex small molecules can generate
      targeted derivatives with exceptional step efficiency, but general strategies for
      maximizing selectivity in this context are rare. Here, we report that site
      selectivity can be tuned by simply modifying the electronic nature of the
      reagents. A Hammett analysis is consistent with linking this phenomenon to the
      Hammond postulate: electronic tuning to a more product-like transition state
      amplifies site-discriminating interactions between a reagent and its substrate.
      This strategy transformed a minimally site-selective acylation reaction into a
      highly selective and thus preparatively useful one. Electronic tuning of both an
      acylpyridinium donor and its carboxylate counterion further promoted site
      divergent functionalizations. With these advances, we achieve a range of
      modifications to just one of the many hydroxyl groups appended to the ion channel
      forming natural product amphotericin B. Thus, electronic tuning of reagents
      represents an effective strategy for discovering and optimizing site-selective
      functionalization reactions.

PMID- 23174980
TI  - Synthesis of a metallic mesoporous pyrochlore as a catalyst for lithium-O2
      batteries.
AB  - The lithium-O2 'semi-fuel' cell based on the reversible reaction of Li and O2 to
      form Li2O2 can theoretically provide energy densities that exceed those of Li-ion
      cells by up to a factor of five. A key limitation that differentiates it from
      other lithium batteries is that it requires effective catalysts (or 'promoters')
      to enable oxygen reduction and evolution. Here, we report the synthesis of a
      novel metallic mesoporous oxide using surfactant templating that shows promising
      catalytic activity and results in a cathode with a high reversible capacity of
      10,000 mAh g(-1) (~1,000 mAh g(-1) with respect to the total electrode weight
      including the peroxide product). This oxide also has a lower charge potential for
      oxygen evolution from Li2O2 than pure carbon. The properties are explained by the
      high fraction of surface defect active sites in the metallic oxide, and its
      unique morphology and variable oxygen stoichiometry. This strategy for creating
      porous metallic oxides may pave the way to new cathode architectures for the Li
      O2 cell.

PMID- 23174981
TI  - Uranium and manganese assembled in a wheel-shaped nanoscale single-molecule
      magnet with high spin-reversal barrier.
AB  - Discrete molecular compounds that exhibit both magnetization hysteresis and slow
      magnetic relaxation below a characteristic 'blocking' temperature are known as
      single-molecule magnets. These are promising for applications including memory
      devices and quantum computing, but require higher spin-inversion barriers and
      hysteresis temperatures than currently achieved. After twenty years of research
      confined to the d-block transition metals, scientists are moving to the f-block
      to generate these properties. We have now prepared, by cation-promoted self
      assembly, a large 5f-3d U(12)Mn(6) cluster that adopts a wheel topology and
      exhibits single-molecule magnet behaviour. This uranium-based molecular wheel
      shows an open magnetic hysteresis loop at low temperature, with a non-zero
      coercive field (below 4 K) and quantum tunnelling steps (below 2.5 K), which
      suggests that uranium might indeed provide a route to magnetic storage devices.
      This molecule also represents an interesting model for actinide nanoparticles
      occurring in the environment and in spent fuel separation cycles.

PMID- 23174982
TI  - Extreme oxatriquinanes and a record C-O bond length.
AB  - Oxatriquinanes are fused, tricyclic oxonium ions that are known to have
      exceptional stability compared to simple alkyl oxonium salts. C-O bonds in ethers
      are generally ~1.43 A in length, but oxatriquinane has been found to have C-O
      bond lengths of 1.54 A. A search of the Cambridge Structural Database turned up
      no bona fide C-O bond length exceeding this value. Computational modelling of
      oxatriquinane alongside other alkyl oxonium ions indicated that the electronic
      consequences of molecular strain were primarily responsible for the observed bond
      elongation. We also show that substitution of the oxatriquinane ring system with
      alkyl groups of increasing steric demand pushes the C-O bond to unheard of
      distances, culminating in a tert-butyl derivative at a predicted 1.60 A. Chemical
      synthesis and an X-ray crystallographic study of these compounds validated the
      results of the modelling work and, finally, an extraordinary 1.622 A C-O bond was
      observed in 1,4,7-tri-tert-butyloxatriquinane.

PMID- 23174983
TI  - An N-bridged high-valent diiron-oxo species on a porphyrin platform that can
      oxidize methane.
AB  - High-valent oxo-metal complexes are involved in key biochemical processes of
      selective oxidation and removal of xenobiotics. The catalytic properties of
      cytochrome P-450 and soluble methane monooxygenase enzymes are associated with
      oxo species on mononuclear iron haem and diiron non-haem platforms, respectively.
      Bio-inspired chemical systems that can reproduce the fascinating ability of these
      enzymes to oxidize the strongest C-H bonds are the focus of intense scrutiny. In
      this context, the development of highly oxidizing diiron macrocyclic catalysts
      requires a structural determination of the elusive active species and elucidation
      of the reaction mechanism. Here we report the preparation of an Fe(IV)(u
      nitrido)Fe(IV) = O tetraphenylporphyrin cation radical species at -90  degrees C,
      characterized by ultraviolet-visible, electron paramagnetic resonance and
      Mossbauer spectroscopies and by electrospray ionization mass spectrometry. This
      species exhibits a very high activity for oxygen-atom transfer towards alkanes,
      including methane. These findings provide a foundation on which to develop
      efficient and clean oxidation processes, in particular transformations of the
      strongest C-H bonds.

PMID- 23174984
TI  - Shape-selective sieving layers on an oxide catalyst surface.
AB  - New porous materials such as zeolites, metal-organic frameworks and
      mesostructured oxides are of immense practical utility for gas storage,
      separations and heterogeneous catalysis. Their extended pore structures enable
      selective uptake of molecules or can modify the product selectivity
      (regioselectivity or enantioselectivity) of catalyst sites contained within.
      However, diffusion within pores can be problematic for biomass and fine
      chemicals, and not all catalyst classes can be readily synthesized with pores of
      the correct dimensions. Here, we present a novel approach that adds reactant
      selectivity to existing, non-porous oxide catalysts by first grafting the
      catalyst particles with single-molecule sacrificial templates, then partially
      overcoating the catalyst with a second oxide through atomic layer deposition.
      This technique is used to create sieving layers of Al(2)O(3) (thickness, 0.4-0.7
      nm) with 'nanocavities' (<2 nm in diameter) on a TiO(2) photocatalyst. The
      additional layers result in selectivity (up to 9:1) towards less hindered
      reactants in otherwise unselective, competitive photocatalytic oxidations and
      transfer hydrogenations.

PMID- 23174985
TI  - A flow-system array for the discovery and scale up of inorganic clusters.
AB  - The batch synthesis of inorganic clusters can be both time consuming and limited
      by a lack of reproducibility. Flow-system approaches, now common in organic
      synthesis, have not been utilized widely for the synthesis of clusters. Herein we
      combine an automated flow process with multiple batch crystallizations for the
      screening and scale up of syntheses of polyoxometalates and manganese-based
      single-molecule magnets. Scale up of the synthesis of these architectures was
      achieved by programming a multiple-pump reactor system to vary reaction
      conditions sequentially, and thus explore a larger parameter space in a shorter
      time than conventionally possible. Also, the potential for using the array as a
      discovery tool is demonstrated. Successful conditions for product isolation were
      identified easily from the array of reactions, and a direct route to 'scale up'
      was then immediately available simply by continuous application of these flow
      conditions. In all cases, large quantities of phase-pure material were obtained
      and the time taken for the discovery, repetition and scale up decreased.

PMID- 23174988
TI  - Plutonium's new horizons.

PMID- 23174986
TI  - Twin disulfides for orthogonal disulfide pairing and the directed folding of
      multicyclic peptides.
AB  - Multicyclic peptides are emerging as an exciting platform for drug and targeted
      ligand discovery owing to their expected greater target
      affinity/selectivity/stability versus linear or monocyclic peptides. However,
      although the precise pairing of cysteine residues in proteins is routinely
      achieved in nature, the rational pairing of cysteine residues within polypeptides
      is a long-standing challenge for the preparation of multicyclic species
      containing several disulfide bridges. Here, we present an efficient and
      straightforward approach for directing the intermolecular and intramolecular
      pairing of cysteine residues within peptides using a minimal CXC motif.
      Orthogonal disulfide pairing can be exploited in complex redox media to
      rationally produce dimeric peptides and bi/tricyclic peptides from fully reduced
      peptides containing 1-6 cysteine residues. This strategy, which does not rely on
      extensive manipulation of the primary sequence, post-translational modification
      or protecting groups, should greatly benefit the development of multicyclic
      peptide therapeutics and targeting ligands.

PMID- 23174989
TI  - Fasting predisposes to hypoglycemia in Surinamese children with severe pneumonia,
      and young children are more at risk.
AB  - The objective of this study was to investigate glucose kinetics during controlled
      fasting in children with severe pneumonia. Plasma glucose concentration,
      endogenous glucose production and gluconeogenesis were measured in 12 Surinamese
      children (six young: 1-3 years, six older: 3-5 years) with severe pneumonia
      during a controlled 16 h fast using stable isotopes [6,6-(2)H2]glucose and (2)H2O
      at a hospital-based research facility. On admission, the glucose concentrations
      were comparable in both groups: young children: 5.1 +/- 1.3 mmol/l, older
      children: 4.8 +/- 0.6 mmol/l, p = 0.685, with a decrease during the first 8 h of
      fasting in the young children only to 3.6 +/- 0.5, p = 0.04. Glucose production
      was comparable in both groups: young: 24.5 +/- 8.3, older: 24.9 +/- 5.9
      umol/kg(*)min, p = 0.926. Between 8 and 16 h of fasting, the glucose
      concentration decreased comparably in both groups (young: - 0.9 +/- 0.7, p =
      0.004; older: -1.0 +/- 0.4 mmol/l, p = 0.001), as did glucose production (young: 
      6.8 +/- 6.3, p = 0.003; older: -5.3 +/- 3.4 umol/kg(*)min, p = 0.001).
      Gluconeogenesis decreased in young children only: -5.0 +/- 7.4, p = 0.029. We
      conclude that fasting predisposes to hypoglycemia in children with severe
      pneumonia. Young children are more at risk than older children. Glucose
      production is an important determinant of the plasma glucose concentration in
      young children with pneumonia, indicating an inability to reduce glucose usage.
      Our results are largely in agreement with the literature on the adaptation of
      glucose metabolism in children with malaria, although there seem to be disease
      specific differences in the regulation of gluconeogenesis.

PMID- 23174990
TI  - Using three delays model to understand the social factors responsible for
      neonatal deaths in rural Haryana, India.
AB  - OBJECTIVE: To investigate causes of and contributors to newborn deaths in rural
      Haryana using a three delays audit approach. METHODS: The study was conducted in
      28 villages under the rural field practice area of the Comprehensive Rural Health
      Services Project, All India Institute of Medical Sciences situated in Ballabgarh,
      Haryana. Data were collected through house visits and analysed using the three
      delays model. RESULTS: Of the 50 newborn deaths investigated, 44% occurred within
      the first 24 h after birth. The leading causes of death were pre-term/low
      birthweight (32%), birth asphyxia (28%) and neonatal sepsis (14%). Major
      contributing delays to neonatal death were caretaker's delay in deciding to seek
      care (44%, 22/50) and delay in reaching a health care facility, i.e. the
      transport delay (34%, 17/50). CONCLUSIONS: Household and transport-related delays
      were the major contributors to newborn deaths, and efforts to improve newborn
      survival need to address both concurrently.

PMID- 23174991
TI  - Para-aminosalicylic acid plasma concentrations in children in comparison with
      adults after receiving a granular slow-release preparation.
AB  - There are no paediatric data regarding slow-release para-aminosalicylic acid
      (PAS). We studied PAS plasma concentrations in 10 children receiving a single 150
      mg/kg dose daily or 75 mg/kg twice daily and 12 adults receiving 4 g twice daily.
      Blood specimens pre-dose and 2, 4, 6, 8 and 12 h post-dose from the children and
      2, 3, 4, 5, 6, 8 and 12 h post-dose from the adults were analysed by high
      performance liquid chromatography MS/MS. The mean Cmax in children receiving PAS
      75 mg/kg and 150 mg/kg and adults receiving 4 g was 45.40, 56.49 and 51.3 ug/ml,
      respectively (p = 0.614); the AUC0-12 was 233.3, 277.9 and 368.0 ug/h/ml (p =
      0.587). No parameters differed significantly between children and adults nor
      between the two doses in the same children. A 150 mg/kg PAS dosage given as one
      or two daily doses leads to plasma concentrations in children similar to those of
      adults receiving 4 g PAS twice daily.

PMID- 23174992
TI  - Visualization of small lesions in rat cartilage by means of laboratory-based x
      ray phase contrast imaging.
AB  - Being able to quantitatively assess articular cartilage in three-dimensions (3D)
      in small rodent animal models, with a simple laboratory set-up, would prove
      extremely important for the development of pre-clinical research focusing on
      cartilage pathologies such as osteoarthritis (OA). These models are becoming
      essential tools for the development of new drugs for OA, a disease affecting up
      to 1/3 of the population older than 50 years for which there is no cure except
      prosthetic surgery. However, due to limitations in imaging technology, high
      throughput 3D structural imaging has not been achievable in small rodent models,
      thereby limiting their translational potential and their efficiency as research
      tools. We show that a simple laboratory system based on coded-aperture x-ray
      phase contrast imaging (CAXPCi) can correctly visualize the cartilage layer in
      slices of an excised rat tibia imaged both in air and in saline solution.
      Moreover, we show that small, surgically induced lesions are also correctly
      detected by the CAXPCi system, and we support this finding with histopathology
      examination. Following these successful proof-of-concept results in rat
      cartilage, we expect that an upgrade of the system to higher resolutions
      (currently underway) will enable extending the method to the imaging of mouse
      cartilage as well. From a technological standpoint, by showing the capability of
      the system to detect cartilage also in water, we demonstrate phase sensitivity
      comparable to other lab-based phase methods (e.g. grating interferometry). In
      conclusion, CAXPCi holds a strong potential for being adopted as a routine
      laboratory tool for non-destructive, high throughput assessment of 3D structural
      changes in murine articular cartilage, with a possible impact in the field
      similar to the revolution that conventional microCT brought into bone research.

PMID- 23174993
TI  - Fibrates as adjuvant therapy for chronic cholestatic liver disease: its time has
      come.

PMID- 23174994
TI  - Early pancreas transplant improves motor nerve conduction in alloxan-induced
      diabetic rats.
AB  - The purpose of this study was to assess the temporal relationship between
      pancreas transplant and the development of electrophysiological changes in the
      sciatic and caudal nerves of alloxan-induced diabetic rats. Nerve conduction
      studies were performed in diabetic rats subjected to pancreas transplantation at
      4, 12, and 24 weeks after diabetes onset, using non-diabetic and untreated
      diabetic rats as controls. Nerve conduction data were significantly altered in
      untreated diabetic control rats up to 48 weeks of follow-up in all time points.
      Rats subjected to pancreas transplantation up to 4 and 12 weeks after diabetes
      onset had significantly increased motor nerve conduction velocity with
      improvement of wave amplitude, distal latency, and temporal dispersion of
      compound muscle action potential in all follow-up periods (P<0.05); these
      parameters remained abnormal when pancreas transplantation were performed late at
      24 weeks. Our results suggest that early pancreas transplant (at 4-12 weeks) may
      be effective in controlling diabetic neuropathy in this in vivo model.

PMID- 23174995
TI  - Ectopic parathyroid glands and their anatomical, clinical and surgical
      implications.
AB  - Ectopic parathyroid glands result from aberrant migration during early stages of
      development and lack of successful identification may lead to lack of success in
      parathyroid surgery. They constitute a common etiology of persistent or recurrent
      hyperparathyroidism, when they are missed at initial diagnosis. Their prevalence
      is about 2-43% in anatomical series and up to 16% and 14% in patients with
      primary and secondary hyperparathyroidism, respectively. Ectopic inferior
      parathyroids are most frequently found in the anterior mediastinum, in
      association with the thymus or the thyroid gland, while the most common position
      for ectopic superior parathyroids is the tracheoesophageal groove and
      retroesophageal region. Neck ultrasound and 99mTc Sestamibi scan are first-line
      imaging modalities, although with low sensitivity and specificity. However, their
      combination with modern techniques, such as single photon emission computed
      tomography (SPECT) alone or in combination with CT (SPECT/CT) increases their
      diagnostic accuracy. Fine needle-aspiration cytology of a lesion suspicious for
      parathyroid tissue and measurement of parathyroid hormone (PTH) in the aspired
      material further assist to the successful preoperative localization of ectopic
      glands. Common sites for surgical investigation are the upper thyroid pole and
      the upper vascular thyroid stalk behind the hypopharynx and cervical esophagus
      for the superior parathyroids, and the carotid artery bifurcation and the thymic
      tongue, for the inferior parathyroids. Radioguided minimally invasive
      parathyroidectomy after successful localization, assisted by rapid PTH
      measurement postoperatively, significantly improves surgical outcomes in patients
      with ectopic parathyroid adenomas.

PMID- 23174996
TI  - The novel adipokine C1q/TNF-related protein-3 is expressed in human adipocytes
      and regulated by metabolic and infection-related parameters.
AB  - BACKGROUND: The growing family of C1Q/TNF-related proteins is characterized by
      structural homologies to the anti-inflammatory adipokine adiponectin. CTRP-3 was
      recently reported to function as an anti-inflammatory LPS-antagonist in vitro.
      MATERIAL AND METHODS: Human subcutaneous and visceral adipocytes and murine 3T3
      L1 adipocytes were used for analysis of CTRP-3 expression and function. Western
      blot analysis of CTRP-3, siRNA mediated knockdown of CTRP-3, Oil red O staining,
      assessment of basal and epinephrine-induced lipolysis, ELISA-based measurements
      of supernatant chemokines, recombinant CTRP-3 protein expression, and
      Staphylococcus aureus (S. aureus) infection assays were used. RESULTS: CTRP-3 is
      expressed in subcutaneous and visceral adipocytes. CTRP-3 is positively regulated
      by insulin, whereas chronic LPS-exposure inhibits terminal adipocyte
      differentiation and CTRP-3 expression. Intracellular infection of adipocytes by
      S. aureus also decreases CTRP-3 expression. As demonstrated by siRNA-mediated
      cellular knockdown of CTRP-3 in adipocytes, CTRP-3 regulates resistin secretion
      and lipolysis. CONCLUSION: CTRP-3 is expressed in human adipocytes and plays an
      important role in adipocyte physiology such as lipolysis and adipokine secretion.
      Both, metabolic factors and infection/inflammation-related factors regulate CTRP
      3 expression.

PMID- 23174998
TI  - Effect of transcatheter arterial chemoembolization prior to surgical resection
      for hepatocellular carcinoma.
AB  - The aim of the present study was to evaluate the influence of preoperative
      transcatheter arterial chemoembolization (TACE) on survival after surgical
      resection (SR) for hepatocellular carcinoma (HCC). Two hundred and thirty-five
      HCC patients who underwent SR with curative intent were analyzed. Overall
      survival (OS), recurrence-free survival (RFS) and complication rates were
      compared between the TACE (n=110) and control groups (n=125). Moreover, TACE
      subjects were classified into TACE responders (n=85) and TACE non-responders
      (n=25), according to the therapeutic efficacy of pretreatment TACE, and the
      factors contributing to OS and RFS after SR were analyzed using univariate and
      multivariate analyses. The 1-, 3- and 5-year OS rates were 87.4, 76.0 and 62.5%,
      respectively, in the TACE group and 94.9, 79.0 and 57.8%, respectively, in the
      control group (P=0.674). The corresponding RFS rates at 1, 3 and 5 years were
      73.3, 48.9 and 33.2%, respectively, in the TACE group and 73.3, 29.4 and 16.3%,
      respectively, in the control group (P=0.062). No TACE-related serious adverse
      events (SAEs) were observed. There were no significant differences between the
      groups in terms of surgery-related SAEs (P=0.714), operation time (P=0.881),
      blood loss during surgery (P=0.334) and hospitalization period (P=0.447).
      Multivariate analyses identified TACE responder, TACE non-responder, total
      bilirubin >=1 mg/dl, serum albumin >=4 g/dl, pretreatment alpha-fetoprotein (AFP)
      level >=100 ng/ml and microscopic vascular invasion as significant prognostic
      factors linked to OS. TACE non-responder, tumor number (multiple) and
      pretreatment AFP level >=100 ng/ml were significant adverse prognostic factors
      linked to RFS. In conclusion, TACE is a safe procedure in patients with HCC, and
      the efficacy of TACE prior to surgery may be associated with clinical outcomes
      after SR.

PMID- 23174997
TI  - Attenuation of exogenous angiotensin II stress-induced damage and apoptosis in
      human vascular endothelial cells via microRNA-155 expression.
AB  - Numerous studies have indicated that cells and tissues have means of blocking
      their response to continuous stress signals to protect themselves from damage.
      Overexpression of angiotensin II (Ang II) in the renin-angiotensin system can
      cause vascular endothelial damage, but the mechanism of adjustment of the dynamic
      equilibrium remains unclear. In this study, we investigated whether microRNA-155
      (miR-155) can suppress continuous Ang II stress signals that would otherwise
      cause vascular endothelial damage. We isolated and cultured human umbilical vein
      endothelial cells (HUVECs) and transfected one group of these with a mature miR
      155 expression plasmid. Quantitative real-time PCR (qRT-PCR) and western blotting
      showed Ang II type 1 receptor expression to be decreased in miR-155-transfected
      HUVECs compared with untransfected cells. The MTT proliferation assay revealed
      that exogenous Ang II suppressed proliferation of HUVECs in a concentration
      dependent manner. When HUVECs were cultured in medium containing Ang II at the
      half maximal inhibitory concentration (68.94 ng/ul) for 24 h, qRT-PCR and western
      blotting showed that expression of the apoptosis inhibitor Bcl-2 in the HUVEC-Ang
      II group was markedly lower than that in controls, but apoptosis-promoting
      factors (Bax, cytochrome c, caspases-9 and -3) were not. Co-immunoprecipitation
      western blotting and immunofluorescence staining showed that exogenous Ang II
      increased the phosphorylation and activation of extracellular signal related
      kinase (ERK)1/2. Exogenous Ang II also influenced HUVEC migration and capillary
      tubule formation in vitro. However, after transfection of HUVECs with miR-155
      under the same conditions, expression of apoptosis-promoting factors and ERK1/2
      phosphorylation were reduced significantly and HUVEC migration and capillary
      tubule formation were restored to some extent. Thus, miR-155 attenuated the
      effect of exogenous Ang II-induced ERK1/2 activation to reduce HUVEC damage and
      apoptosis. Moreover, miR-155 maintained HUVEC migration and capillary tubule
      formation in vitro.

PMID- 23174999
TI  - Leptomeningeal metastasis from squamous cell carcinoma of oesophagus with unusual
      presentation.
AB  - Oesophageal cancer rarely metastasis to the brain but advances in brain imaging
      and increasing survival of these patients has led to more detection of this
      condition. Although oesophageal cancer is common in the north of Iran it is less
      frequent in the central parts such as Yazd. Leptomeningeal metastasis is very
      uncommon in oesophageal cancer. This paper presents a 73-year-old man with
      leptomeningeal carcinomatosis from squamous cell carcinoma of oesophagus
      presented by hoarseness due to true vocal cord plegia.

PMID- 23175000
TI  - Metastatic haematological malignancy presenting as a sellar mass.
AB  - A man in his 60s with a history of multiple myeloma diagnosed 6&emsp14;months
      previously was referred with a diagnosis of a sellar mass. He reported a 3-month
      history of headaches associated with double vision which appeared to improve with
      corticosteroid treatment. An MRI scan revealed a 3.7 cm * 3 cm * 2.6 cm sellar
      mass with erosion into the sphenoid sinus and extending to the right cavernous
      sinus. Pituitary function tests were normal apart from hypogonadotrophic
      hypogonadism. A diagnosis of plasmacytoma was considered and so transphenoidal
      biopsy of the sellar lesion was organised, which revealed sheets of mature
      appearing plasma cells, staining exclusively for kappa-light chain
      immunoglobulins. He was to be started on chemotherapy for the myeloma and
      radiotherapy for the plasmacytoma. The patient's clinical course was complicated
      by community-acquired pneumonia and renal failure resulting in his death a month
      after the diagnosis of plasmacytoma.

PMID- 23175001
TI  - Eccentric superior mesenteric artery calcification in a haemodialysis patient.

PMID- 23175003
TI  - Traumatic right ventricular rupture following a horse kick.
AB  - Cardiac tamponade is a life-threatening and time-critical emergency that requires
      early recognition and prompt management often alongside other resuscitation
      considerations. The use of ultrasound in the primary survey greatly assists in
      the early diagnosis allowing preparations for early definitive management to be
      made. An unusual case of right ventricular rupture following blunt trauma to the
      chest from a horse kick is discussed.

PMID- 23175002
TI  - High-dose insulin therapy for neurogenic-stunned myocardium after stroke.
AB  - A 44-year-old woman with a history of complicated type 2 diabetes mellitus
      presented with a diagnosis of right-hemispheric ischaemic stroke. She developed
      acute respiratory distress with radiological evidence of pulmonary oedema. The
      ECG showed poorly significant ST-segment changes, with a minimal increase of
      cardiac biomarkers. Echocardiography showed a severely depressed left ventricular
      function, with also low values of cardiac output at invasive monitoring. The
      possibility of neurogenic-stunned myocardium was discussed and a metabolic
      resuscitation with high-dose insulin was proposed. An intravenous bolus of 80
      units of insulin (0.72 IU/kg) was followed by a continuous infusion at the rate
      of 160 IU/h (1.45 IU/kg/h). The treatment led to a rapid and sustained
      improvement of the haemodynamic condition and was well tolerated. In comparison
      with dobutamine, insulin had significant inotropic effects without tachycardia.
      The patient unfortunately died on day 35, from respiratory complications after
      poor neurological recovery.

PMID- 23175004
TI  - Anomalous venous circuit: a detour to the heart.
AB  - We report a case of a complicated vascular access secondary to systemic venous
      defects, which have not been previously reported. Evaluation revealed an atypical
      coursing of a subclavian vein-persistent superior vena caval system into the
      hemizygos-azygos system and ultimately into the right (proper) superior vena
      cava. The clinical and surgical considerations of such an anomaly are discussed
      therein. We look at embryological origins of such a merger and share our
      experience in troubleshooting through the anomaly.

PMID- 23175005
TI  - An unusual case of Parinaud's syndrome.
AB  - A 25-year-old man presented with blurred vision, headache and dizziness. On
      questioning, there was also a history of a preceding diarrhoeal illness. Initial
      investigations were normal. However, after a week, he represented with a
      Parinaud's syndrome. In view of the preceding diarrhoea, the transient
      unsteadiness and the areflexia on examination, anti-GQ1b antibodies were
      requested. The resulting titre was positive confirming the suspected diagnosis of
      Miller Fisher syndrome. He responded to intravenous immunoglobulins with full
      resolution of his symptoms and signs. Although various unusual neuro
      ophthalmological signs have been reported localising to the brainstem, to our
      knowledge, this is the first case report of Parinaud's syndrome being the
      presenting symptom of Miller Fisher syndrome.

PMID- 23175006
TI  - Clinical improvement precedes lesion size regression in a severe case of acute
      disseminated encephalomyelitis.
AB  - Here, we present a case of a severe acute disseminated encephalomyelitis (ADEM)
      of a 42-year-old male patient. The diagnosis was established after brain biopsy
      and due to acutely evolving encephalopathy occurring in the context of atypical
      Mycoplasma pneumoniae (MP). We analysed the prominent MRI white matter lesions
      using a three-dimensional algorithm as cutting-edge technique to study
      morphological abnormalities and correlated them to the clinical condition of the
      patient. We found a discrepancy between the lesion size and the clinical deficits
      of the patient, actually the clinical improvement antedated the regression of the
      white matter lesions.

PMID- 23175007
TI  - A child with bone fractures and dysmorphic features: remember of pycnodysostosis
      and craniosynostosis.
AB  - Accidental bony injuries are common in children. Children may also present with
      bony injuries following non-accidental injuries. Pathological fractures, though
      extremely rare, are an important entity and constitute fractures that occur in
      abnormal bones, usually after minor trauma. Pycnodysostosis is a rare skeletal
      dysplasia characterised by a clinical phenotype that includes short stature,
      skull deformities, osteosclerosis, acroosteolysis and bone fragility. Often the
      disease is diagnosed at an early age as a result of the investigation of short
      stature. However, the diagnosis is sometimes delayed and must be considered in
      any child with a history of recurrent or multiple bone fractures and dysmorphic
      features. The purpose of this report is to describe the clinical, radiological
      and genetic issues of a 9-year-old girl with a long history of multiple bone
      fractures. She had been subjected to safeguarding investigations previously and
      was identified to have dysmorphic features diagnosed as pycnodysostosis
      associated with craniosynostosis.

PMID- 23175008
TI  - Accessory mitral valve without subaortic obstruction of left ventricular outflow
      tract in a middle-aged male.
AB  - Accessory mitral valve (AMV) is a rare congenital abnormality with a usually
      early-age clinical onset, being potentially a cause of subvalvular obstruction of
      the left ventricular outflow tract. This report describes the case of a 60-year
      old patient presented with palpitations and chest pain. Primary evaluation
      revealed a ventricular tachycardia episode while transthoracic echocardiography
      showed an intracardiac additional structure at the level of the left ventricular
      outflow tract. After transoesophageal echocardiography and paraclinical
      investigations this structure was proven to be an AMV tissue which did not
      provoke left ventricular outflow obstruction. This case presents an unusual late
      age clinical onset of AMV without a clinically significant LVOT (left ventricular
      outflow tract) obstruction and highlights the importance of transthoracic and
      transoesophageal echocardiography in the diagnosis of this rare cardiological
      entity.

PMID- 23175009
TI  - Jejunal intussusception: a cause of upper gastrointestinal bleeding?
AB  - Intussusception is an important cause of abdominal pain in the paediatric
      population and is the most common abdominal emergency in early childhood.
      Intussusception in adults is, however, rare and can lead to diagnostic challenges
      for admitting physicians/surgeons. We present a case of a 76-year-old lady with
      history of a recent myocardial infarction and vasculitis presenting with melaena
      and bleeding per rectum, with suspicion of haematochezia. She complained of
      abdominal pain but was not clinically obstructed. Gastroscopy performed was
      negative. Colonoscopy was attempted; however, it was inconclusive because of
      active bleeding. A CT angiogram of the abdomen was performed, which showed a
      jejunal intussusception. There was no evidence of vasculitis or small bowel
      obstruction. She was not considered fit for surgery and was managed
      conservatively.

PMID- 23175010
TI  - Anticoagulant-induced priapism progressing to penile gangrene: a devastating
      complication!
AB  - A 35-year-old man developed priapism with the use of low-molecular-weight heparin
      and warfarin following repair of left brachial artery sustained after gunshot
      injury. Priapism progressed to penile gangrene despite decompression and distal
      shunt procedure leading to total penectomy and perineal urethrostomy. We describe
      the mechanism of anticoagulant (heparin and warfarin)-induced penile gangrene and
      the possible methods to avert such a devastating complication.

PMID- 23175011
TI  - Primary ovarian pregnancy: case report and review of literature.
AB  - A young woman in her 20s presented with sudden onset right-sided abdominal pain.
      On examination she was tender in the right adnexae. Her urine pregnancy test was
      positive and betaHCG value was 1862. Abdominal and pelvic ultrasound revealed
      evidence of a significant right-sided adnexal mass, a small amount of peritoneal
      free fluid and an empty uterus. The decision was made to proceed with laparoscopy
      in view of mass size and the presence of fluid in the pelvis. Conservative
      resection of the gestational sac was performed and the patient made an uneventful
      recovery. Histology was consistent with ovarian ectopic pregnancy.

PMID- 23175012
TI  - Pop goes the O2: a case of popper-induced methaemoglobinamia.
AB  - A 39-year-old man presented to the emergency department after falling downstairs
      after he consumed a large quantity of alcohol. On examination, he had altered
      mental state (GCS 14), central cyanosis and low oxygen saturation of 86%, despite
      100% oxygen being administered. His arterial blood gas confirmed diagnosis of
      methaemoglobinaemia with a methaemoglobin percentage of 14.08. He was treated
      successfully with methylthioninium chloride. The patient later admitted to use of
      recreational poppers (amyl nitrates) the previous evening. The emergency
      physician is challenged by the presentation of a patient with altered mental
      state and unexplained low oxygen saturation with concurrent alcohol intoxication
      but must have a high index of suspicion for methaemoglobinaemia particularly with
      a history of recreational drug ingestion.

PMID- 23175013
TI  - Central venous catheter embolisation.
AB  - Tunnelled central venous catheters are commonly used for a variety of
      indications, including home parenteral nutrition, but are rarely associated with
      fracture and embolisation; the risk of embolisation is reported to be greater
      with catheters placed via the subclavian vein rather than the internal jugular
      route. We report the case of a 64-year-old woman with type 3 (chronic and
      irreversible) intestinal failure who presented with pain and swelling on infusion
      of parenteral nutrition through her internal jugular catheter. A chest x-ray
      showed fracture and embolisation of her catheter into the right ventricle. The
      embolised portion was retrieved and removed via the femoral route, without
      complication and the catheter replaced. We discuss causes of line embolisation,
      and highlight the possibility of embolisation occurring with an internal jugular
      catheter.

PMID- 23175014
TI  - Left ventricular clot in a patient with stroke.

PMID- 23175015
TI  - Dysplasia epiphysealis hemimelica: a huge articular mass with unpredictable
      surgical results.
AB  - Dysplasia epiphysealis hemimelica or Trevor's disease is a rare disorder of
      localised osteochondral overgrowth affecting the epiphysis of extremities. This
      paper reports a 12-year-old boy presenting with a large bony mass at the left
      ankle diagnosed as dysplasia epiphysealis hemimelica. The articular surface of
      the ankle joint of the patient was evaluated with preoperative and postoperative
      MRIs. The 2-year postoperative MRI showed early osteoarthritis of the ankle,
      therefore demonstrating the importance of early excision avoiding more complex
      resections of intra-articular lesions.

PMID- 23175016
TI  - Dermatofibrosarcoma: a rare neoplasm of skin.
AB  - A 25-year-old lady presented with a small pea-sized lesion on left side of her
      neck, anteriorly. There was no history of any other lesion on her body. She was
      medically fit otherwise. An excision was planned, after taking consent from her,
      which was performed under local anaesthesia as a day procedure. Her postoperative
      recovery was uneventful. Histopathology showed dermatofibrosarcoma protuberance
      which is an extremely rare skin tumour. She was further investigated for
      metastasis. Her CT scan of chest, abdomen and pelvis was performed which showed
      prominent thymus. Other than this finding, no other abnormality was found in CT
      scan.

PMID- 23175017
TI  - Levamisole-induced vasculitis with ecchymosis and necrosis syndrome from
      contaminated cocaine.

PMID- 23175018
TI  - Splenic rupture visualised with focused assessment with sonography for trauma
      (FAST): heterogeneous echogenicity of acute haemorrhage following blunt trauma.

PMID- 23175019
TI  - Ruptured aortic dissection presenting with new onset atrial fibrillation.
AB  - We report this type A aortic dissection in both ascending and descending thoracic
      aorta presenting with new onset atrial fibrillation. CT images confirmed the
      final diagnosis. The mechanism may be due to compression of the left atrium by a
      large haematoma.

PMID- 23175020
TI  - Pathological fracture of femur secondary to infected synovial sarcoma.
AB  - Pathological fracture is not uncommon in musculoskeletal oncological surgical
      practice. When complicated by infection, it is both limb- threatening and life
      threatening problem. Pathological fractures require urgent investigation, not
      urgent treatment. We present the case of a 75-year-old man who presented with an
      infected sarcoma causing a pathological fracture of his right femur.

PMID- 23175021
TI  - The occult nature of intramedullary spinal cord metastases from renal cell
      carcinoma.
AB  - Renal cell carcinomas (RCC) are characterised by a tendency to metastasise
      widely, often while remaining occult. Intramedullary spinal cord metastases
      (ISCM) from RCC may be the presenting feature of the disease or present at any
      time in the disease course. This case report discusses an ISCM from RCC which
      became manifested at the time of resection of the primary tumour. We review the
      literature published on ISCM from RCC from 1990 to date comparing disease
      characteristics and presentations.

PMID- 23175023
TI  - Assessment of the safety of maslinic acid, a bioactive compound from Olea
      europaea L.
AB  - SCOPE: Maslinic acid, the main pentacyclic triterpene of the cuticle of Olea
      europaea L. fruit, has multiple beneficial effects on health, most notably
      antitumor and hypoglycemic properties. Notwithstanding the biological activities,
      there is a lack of knowledge about its safety. Therefore, the purpose of this
      study was to evaluate whether high doses of maslinic acid have harmful effects on
      Swiss CD-1 male mice. METHODS AND RESULTS: The single oral administration of the
      pentacyclic triterpene at 1000 mg/kg to mice did not produce any signs of
      morbidity or mortality. The repeated daily oral administration of 50 mg/kg of
      maslinic acid for 28 days did not induce any sign of toxicity during the
      experimental period. Body weight did not differ between mice that received the
      triterpene and the control group. Similarly, hematological and biochemical
      variables were not affected by the treatment. Histopathologic examination of the
      organs revealed that there were no differences between the control and the
      treated mice. CONCLUSION: Taken together the results obtained from the acute and
      the repeated intake of maslinic acid indicate that the compound does not exert
      any adverse effects on the variables tested in mice, thus suggesting a sufficient
      margin of safety for its putative use as a nutraceutical.

PMID- 23175024
TI  - Special issue: Recognizing Otto Rank, an innovator. Are innovators trouble?

PMID- 23175025
TI  - Rankian will.
AB  - Otto Rank (1884-1939) served as Freud's closest partner in the psychoanalytic
      movement from 1906 to 1926. From 1923 on, Rank, initially with Ferenczi, focused
      on making analysis more therapeutic, emphasizing current experience in the
      session over historical exploration and interpretation. Rank settled on will as a
      missing factor, and wrote extensively about it after the break with Freud in
      1926, when he moved to Paris. He emphasized the here-and-now, redefined
      "resistance" as a positive aspect of counter-will, and suggested a time limit for
      analysis. Ousted from analytic circles in 1930, he eventually moved to New York,
      continuing to treat patients and teach until his unexpected death at 55 in 1939.
      After decades of obscurity, Rank has gained readers and therapists whose
      orientation is interpersonal, client-centered, relational, humanistic, or
      existential. His influence on post-Freudian ego-psychology is finally being
      acknowledged as are his ideas about creativity, will, life-fear and death-fear,
      guilt, and ethics.

PMID- 23175026
TI  - Rank on emotional intelligence, unlearning and self-leadership.
AB  - Propelled from the inner circle after publishing The Trauma of Birth (1924), Otto
      Rank jettisoned Freud's science of knowing because it denied the intelligence of
      the emotions. Transforming therapy from knowing to being-in-relationship, Rank
      invented modern object-relations theory, which advocates continual learning,
      unlearning and relearning: that is, cutting the chains that bind us to the past.
      Separating, no matter how anxiety-provoking, from outworn phases of life,
      including previously taken-for-granted ideologies and internalized others, is
      essential for self-leadership. In 1926, Rank coined the terms "here-and-now" and
      "pre-Oedipal." By 1926, Rank had formulated a model of "creative willing"-self
      leadership infused with the intelligence of the emotions-as the optimal way of
      being-in-relationship with others.

PMID- 23175027
TI  - The Rank-Ferenczi relationship, as seen from France.
AB  - Seen from France, where Rank's "American" work is not well known, the Rank
      Ferenczi relationship does not allow to state that the two learned colleagues
      were the best friends. Rank met Ferenczi in 1908, but their most valuable and
      fruitful working relationship is limited to the 1922-1924 time period. Their
      working relationship must be read in light of the unique transference links of
      each to Freud, and in light of the tormented history of the analytic movement,
      especially after the First World War. The sensible reader will not forget that
      after the fast extinction of their short collaboration they continued their own
      works in their own ways, Otto Rank in Paris and in America and Sandor Ferenczi in
      Budapest. No more friends, nor enemies, but both, in a different style, brave and
      creative analysts.

PMID- 23175028
TI  - The art of living in Otto Rank's Will Therapy.
AB  - Otto Rank's approach to psychotherapy, developed after his separation from Freud,
      encourages living life fully in spite of death and limitation. In his emphasis on
      the here and now, new experience in the therapeutic relationship, and
      collaboration and creativity in the therapy process, Rank was ahead of his time.
      As a theorist of personality and of creativity, his work is well known, but his
      influence on the practices of humanistic, existential, and post-psychoanalytic
      relational therapists is largely unacknowledged. Rank's creative legacy is an
      approach to psychotherapy that calls forth artistry and collaboration between
      therapist and client.

PMID- 23175029
TI  - An exploration in the will psychology of Otto Rank: human intentionality and
      individuality.
AB  - The author explores the meaning and the importance of the will in Rank's relation
      based self-creative, self-constructive psychology and argues for the
      consideration of the concept of the will in psychoanalysis. The paper shows that
      Rank's concept of the will explains what gives a human being the impetus to
      choose an action, positive or negative. When validated by the other, this will,
      the power of intention, enables a person to create his/her unique individuality.
      The paper reviews Rank's definition of will and traces the evolution of his ideas
      of intentionality in his writings. Further, the author discusses how Rank
      attempts to capture the subtle movements of the human mind as suffused with
      struggles and dynamic interplay between external and internal forces.

PMID- 23175030
TI  - Confusion of wills: Otto Rank's contribution to an understanding of childism.
AB  - Drawing from Elisabeth Young-Bruehl's psychological and psychodynamic study of
      prejudice as a starting point, this paper explores the phenomenon of childism
      namely, the prejudice again children-from a Rankian psychodynamic perspective.
      Young-Bruehl argues that childism is comparable to prejudices such as anti
      Semitism, sexism, and racism, and serves such purposes as the elimination of an
      individual's personhood, sexual exploitation, and the erasure of identity. Adding
      to Young-Bruehl's analysis of the social and psychological causes and effects of
      prejudice against children, this paper will examine the nature and dangers of
      childism explicit and implicit in the writings of Otto Rank. We will examine the
      development of creative will in child maturation-a development that childist
      forms of prejudice may obstruct, inhibit, and compromise. We will see that Young
      Bruehl's foundational writing on childism echoes many of the observations and
      writings of Otto Rank in regard to the prejudice against children, and how such
      prejudice deeply diminishes, undermines, and fractures our unfolding lives and
      creative will in a shared world.

PMID- 23175034
TI  - Early lights.

PMID- 23175033
TI  - MR chemical exchange imaging with spin-lock technique (CESL): a theoretical
      analysis of the Z-spectrum using a two-pool R(1rho) relaxation model beyond the
      fast-exchange limit.
AB  - The chemical exchange (CE) process has been exploited as a novel and powerful
      contrast mechanism for MRI, which is primarily performed in the form of chemical
      exchange saturation transfer (CEST) imaging. A spin-lock (SL) technique can also
      be used for CE studies, although traditionally performed and interpreted quite
      differently from CEST. Chemical exchange imaging with spin-lock technique (CESL),
      theoretically based on the Bloch-McConnell equations common to CEST, has the
      potential to be used as an alternative to CEST and to better characterize CE
      processes from slow and intermediate to fast proton exchange rates through the
      tuning of spin-lock pulse parameters. In this study, the Z-spectrum and
      asymmetric magnetization transfer ratio (MTR(asym)) obtained by CESL are
      theoretically analyzed and numerically simulated using a general two-pool R(1rho)
      relaxation model beyond the fast-exchange limit. The influences of spin-lock
      parameters, static magnetic field strength B(0) and physiological properties on
      the Z-spectrum and MTR(asym) are quantitatively revealed. Optimization of spin
      lock frequency and spin-lock duration for the maximum CESL contrast enhancement
      is also investigated. Numerical simulation results in this study are compatible
      with the findings in the existing literature on CE imaging studies.

PMID- 23175035
TI  - Brilliant explosions.

PMID- 23175036
TI  - Why trap light?

PMID- 23175037
TI  - In the limelight. Interview by Kosmas Tsakmakidis.

PMID- 23175043
TI  - Topological insulators: Crystalline protection.

PMID- 23175044
TI  - Applied physics and interfaces: Positively 'negative' friction.

PMID- 23175045
TI  - Lipid multilayers: Domains stack up.

PMID- 23175046
TI  - Cancer therapy: Death by magnetism.

PMID- 23175047
TI  - Artificial motors: Peptide-powered boats.

PMID- 23175048
TI  - Colloidal self-assembly: Superparticles get complex.

PMID- 23175049
TI  - Material witness: Peeling without pain.

PMID- 23175050
TI  - Role of patatin-like phospholipase domain-containing 3 on lipid-induced hepatic
      steatosis and insulin resistance in rats.
AB  - Genome-wide array studies have associated the patatin-like phospholipase domain
      containing 3 (PNPLA3) gene polymorphisms with hepatic steatosis. However, it is
      unclear whether PNPLA3 functions as a lipase or a lipogenic enzyme and whether
      PNPLA3 is involved in the pathogenesis of hepatic insulin resistance. To address
      these questions we treated high-fat-fed rats with specific antisense
      oligonucleotides to decrease hepatic and adipose pnpla3 expression. Reducing
      pnpla3 expression prevented hepatic steatosis, which could be attributed to
      decreased fatty acid esterification measured by the incorporation of [U-(13) C]
      palmitate into hepatic triglyceride. While the precursors for phosphatidic acid
      (PA) (long-chain fatty acyl-CoAs and lysophosphatidic acid [LPA]) were not
      decreased, we did observe an ~20% reduction in the hepatic PA content, ~35%
      reduction in the PA/LPA ratio, and ~60%-70% reduction in transacylation activity
      at the level of acyl-CoA:1-acylglycerol-sn-3-phosphate acyltransferase. These
      changes were associated with an ~50% reduction in hepatic diacylglycerol (DAG)
      content, an ~80% reduction in hepatic protein kinase Cepsilon activation, and
      increased hepatic insulin sensitivity, as reflected by a 2-fold greater
      suppression of endogenous glucose production during the hyperinsulinemic
      euglycemic clamp. Finally, in humans, hepatic PNPLA3 messenger RNA (mRNA)
      expression was strongly correlated with hepatic triglyceride and DAG content,
      supporting a potential lipogenic role of PNPLA3 in humans. CONCLUSION: PNPLA3 may
      function primarily in a lipogenic capacity and inhibition of PNPLA3 may be a
      novel therapeutic approach for treatment of nonalcoholic fatty liver disease
      associated hepatic insulin resistance.

PMID- 23175052
TI  - Probing the tolerance of cucurbit[7]uril inclusion complexes to small structural
      changes in the guest.
AB  - The binding properties of the cucurbit[7]uril host with three structurally
      related ferrocene-containing guests, ferrocenyltrimethylammonium,
      ferrocenylmethyltrimethylammonium and ferrocenylethyltrimethylammonium, have been
      investigated using (1)H NMR spectroscopy, mass spectrometry, voltammetry and
      computational methods. The experimental and computational data indicate that the
      stability of the cucurbit[7]uril inclusion complexes is relatively insensitive to
      the number of methylenes connecting the trimethylammonium and the ferrocenyl
      groups, although some of their properties are affected in significant ways.

PMID- 23175051
TI  - Somatic mutations in the GATA6 gene underlie sporadic tetralogy of Fallot.
AB  - Tetralogy of Fallot (TOF) is the most common cyanotic congenital heart disease
      associated with significant morbidity and mortality in humans. However, the
      molecular etiology underlying TOF in most patients remains largely unknown. In
      the present study, sequence analysis of the GATA6 gene was performed from fresh
      frozen cardiac tissues and matched blood samples of 52 unrelated patients who
      underwent surgical repair of TOF. The cardiac tissues and matched blood specimens
      from 46 patients who underwent cardiac valve replacement due to rheumatic heart
      disease and blood samples from 200 healthy individuals as controls were
      genotyped. The functional characteristics of the mutations were assessed using a
      luciferase reporter assay system. Based on the results, two novel heterozygous
      GATA6 mutations, p.G367X and p.G394C, were identified in the cardiac tissues of 2
      TOF patients, respectively. No mutations were found in the cardiac tissues from
      46 patients with rheumatic heart disease and in the blood samples from the 298
      participants. Functional analysis demonstrated that the GATA6 mutants were
      consistently associated with significantly reduced transcriptional activation
      compared with their wild-type counterpart. This is the first report on the link
      of somatic GATA6 mutation to TOF, providing novel insight into the molecular
      mechanism involved in TOF.

PMID- 23175053
TI  - One on one.

PMID- 23175054
TI  - The golden ratio.

PMID- 23175055
TI  - Left in the dark.

PMID- 23175056
TI  - Autoinjector or vial?

PMID- 23175057
TI  - Real world evidence.

PMID- 23175058
TI  - Secondary care burden.

PMID- 23175059
TI  - Catastrophic injuries.

PMID- 23175071
TI  - Oral physicians.
AB  - In response to Stephen Hancocks' editorial Sawbones no longer, this paper
      examines the future role of oral physicians and patients' need for dental
      professionals to play a larger part in overall healthcare. Whilst the financial
      structures behind the US and UK dental systems differ, it can be questioned
      whether the outcomes of impending change will be as diverse.

PMID- 23175072
TI  - Minimal intervention dentistry: part 3. Paediatric dental care--prevention and
      management protocols using caries risk assessment for infants and young children.
AB  - Recent increases in caries prevalence in young children throughout the world
      highlight the need for a simple but effective infant oral care programme. This
      programme needs to include a medical disease prevention management model with an
      early establishment of a dental home and a treatment approach based on individual
      patient risk. This article presents an updated approach with practical forms and
      tools based on the principles of caries management by risk assessment, CAMBRA.
      This method will aid the general practitioner to develop and maintain a
      comprehensive protocol adequate for infant and young children oral care visits.
      Perinatal oral health is vitally important in preventing early childhood caries
      (ECC) in young children. Providing dental treatment to expectant mothers and
      their young children in a 'dual parallel track' is an effective innovative
      strategy and an efficient practice builder. It promotes prevention rather than
      intervention, and this may be the best way to achieve long-lasting oral health
      for young patients. General dental practice can adopt easy protocols that will
      promote early preventive visits and anticipatory guidance/counselling rather than
      waiting for the need for restorative treatment.

PMID- 23175078
TI  - Summary of: A school-based epidemiological study of dental neglect among
      adolescents in a deprived area of the UK.

PMID- 23175079
TI  - Summary of: A survey of dental hygienists in the United Kingdom in 2011. Part 1-
      demographics and working patterns as dental hygienists.

PMID- 23175080
TI  - Developing the continuum of dental education: including dental foundation
      trainers in the delivery of a community-based clinical teaching programme.
AB  - INTRODUCTION: Despite advances in evidence-based dental school educational
      programmes, the charge is sometimes made that dental students are 'no longer as
      good as they used to be'. Recent modifications have meant that dental education
      is now a 'life-long experience', of which dental school is the initial, albeit
      very important, component. Contemporary dental students will normally enter
      dental foundation (DF) training on completion of dental school. As such there may
      be value in including DF trainers in dental school teaching programmes. The aim
      of this paper is to report the experiences, feedback and opinions of these DF
      trainers following their first-hand experience of the community-based clinical
      teaching programme at Cardiff, and assess if their perspectives of contemporary
      dental student education changed following this. MATERIALS AND METHODS: DF
      trainers were invited to attend the community-based clinical teaching programme
      at Cardiff on an observer basis. Twenty-four DF trainers attended, following
      which evaluation questionnaires were completed. Information sought included
      opinions and attitudes to the teaching programme, the physical environment in
      which the teaching programme took place, knowledge and attitudes towards
      community-based clinical teaching and modifications that DF trainers would make
      to the teaching programme to further improve the knowledge, skills and attributes
      of dental school graduates for DF training. RESULTS: Responses were received from
      20 DF trainers (response rate = 83%). All 20 respondents felt that the teaching
      provided within the community-based clinical teaching programme was appropriate,
      with one respondent noting that it was like 'a day in the life of a dental
      practice', 'where anything could present'. Sixteen respondents were satisfied
      with the scope and content of the community-based clinical teaching programme,
      with a small number recommending inclusion of teaching in relation to
      inlays/onlays (n = 2), simple orthodontics (n = 1) and splinting (n = 1).
      Eighteen respondents reported that they felt students were adequately prepared
      for entry into DF training. All 20 respondents reported that their visit to the
      community-based clinical teaching programme had improved their perception of
      contemporary dental school education with one respondent noting: 'I am certainly
      more confident about students graduating' and another noting: 'It has reassured
      me that there are final year dental students that appear very professional and
      competent'. CONCLUSIONS: This investigation has demonstrated there is much to be
      gained by inclusion of DF trainers in undergraduate dental student community
      based clinical teaching programmes. In an era where tensions exist between dental
      school teaching and subsequent DF training and independent practice, inclusion of
      DF trainers can exert positive pressures on dental school programmes and on DF
      training to ensure that young and newly graduating dentists are best prepared to
      meet the needs of their patients.

PMID- 23175081
TI  - Adult Dental Health Survey 2009: transformations in British oral health 1968
      2009.
AB  - This series of four papers reports and interprets the findings of the Adult
      Dental Health Survey (ADHS), 2009, published in early 2011. This is the fifth in
      a series of surveys repeated every decade since 1968. The evolution of the
      surveys and the way the supporting methodology has changed to meet the changing
      needs and circumstances over the last 40 years is described. In 1968, 37% of
      adults in England and Wales were edentate. By 2009, only 6% of the combined
      population of England, Wales and Northern Ireland were edentate. Among the
      dentate in 1968, there were a mean of 21.9 teeth. By 2009, not only had the
      dentate increased by 30 percentage points as a fraction of the population, but
      the number of teeth in this group had also increased by nearly four teeth on
      average to 25.7. There were significant variations in oral health according to
      geography and social variables and smaller differences according to sex. The
      retention of 21 or more teeth is widely used as a way of defining a minimum
      functional dentition. The proportion of adults with 21+ teeth increased from 73%
      in 1978 to 86% in 2009. Further huge improvements are projected as younger
      generations age, assuming future tooth loss continues at current low rates. We
      might expect that over 90% of those aged 35-44 in 2009 have a realistic prospect
      of retaining a functional natural dentition of 21 or more teeth by age 80.

PMID- 23175099
TI  - A school-based epidemiological study of dental neglect among adolescents in a
      deprived area of the UK.
AB  - OBJECTIVE: To assess the prevalence of two types of dental neglect (DN) for
      adolescents attending secondary schools in a deprived inner city area: neglect of
      the prevention of oral disease (DPN) and neglect of dental treatment (DTN).
      DESIGN: This study used cross-sectional data from Phase III of the research with
      East London adolescents community health survey (RELACHS); a longitudinal school
      based epidemiological study that followed up a representative random sample of
      pupils in 29 secondary schools across three boroughs of inner North East London.
      Participants were clinically examined and answered a supervised questionnaire. DN
      was assessed in relation to DPN (measured by reference to experience of dental
      conditions and/or dental pain) and DTN (measured by reference to experience of at
      least one untreated dental condition and/or dental pain). Dental conditions
      included dental caries and traumatic dental injuries. RESULTS: Four in ten
      adolescents in the study experienced DPN and five in ten experienced DTN.
      Adolescents with special educational needs without a statement, refugee and those
      'looked after' by a local authority experienced a higher proportion of both types
      of DN. CONCLUSIONS: In an inner city deprived area, the proportion of adolescents
      with DN (either DPN or DTN) was of significance. Refugee adolescents and looked
      after children may be more at risk of DN.

PMID- 23175100
TI  - A survey of dental hygienists in the United Kingdom in 2011. Part 1--demographics
      and working patterns as dental hygienists.
AB  - AIMS: The aims of this survey were to establish the demographic profile of dental
      hygienists (DHs) and dental hygienist/therapists (DH/Ts) in the United Kingdom in
      2011 and their patterns of practice as DHs. METHODS: A 10% sample of all those
      registered with the General Dental Council as DHs or DH/Ts in April 2011 were
      sent a pre-piloted questionnaire, explanatory letter and stamped addressed
      envelope. The questionnaire contained a total of 100 questions, 24 of which
      related to demographics and working patterns. All 100 questions were solely on
      tasks/work performed by DH, none related to other types of work performed by
      DH/Ts. Three mailings were distributed between May and July 2011. The resulting
      data were entered into an Excel spreadsheet. Where appropriate, differences
      between the responses from DHs and DH/Ts were statistically tested with the chi
      squared test. RESULTS: Five hundred and sixty-one DHs and DH/Ts were sent the
      questionnaire, by the third mailing 371 (66.1%) had responded and returned
      completed questionnaires. The respondents were 288 DHs, 79 DH/Ts and 4 who did
      not specify which category they were. The mean year of qualification of the DHs
      was 1990 and for the DH/Ts 2005. One hundred and twenty-four (33%) reported that
      they worked full-time, 235 (63%) part-time and the remainder that they were not
      working as DHs or DH/Ts or had retired. The average number of clinical hours
      worked per week was reported as 24.6 hours for DHs and 25 hours for DH/Ts, but
      there were regional variations. For DHs the mean percentage of patients treated
      under NHS contract was 15.5% and for DH/Ts it was 40.2%. Again there were
      regional variations and in Scotland these figures were 45.5% for DHs and 70% for
      DH/Ts. Two hundred and forty-eight (69%) of all respondents were either fully or
      partly self-employed and 221 (62.7%) worked in two or more locations.
      CONCLUSIONS: The results of this study provide a snapshot of the demographics and
      practice patterns of DHs and DH/Ts in the UK in the summer of 2011. They confirm
      the results of a survey that was conducted in England in early 2011 and of a
      survey that took place in Scotland in 2009.

PMID- 23175101
TI  - Induction of apoptosis in A431 skin cancer cells by Cissus quadrangularis Linn
      stem extract by altering Bax-Bcl-2 ratio, release of cytochrome c from
      mitochondria and PARP cleavage.
AB  - Skin is generally damaged through genetic and environmental factors such as
      smoking, exposure to xenobiotics, heat, hormonal changes, and ultraviolet light.
      These factors can cause skin diseases. Cissus quadrangularis Linn. (CQ) has been
      used in folk medicine for the treatment of skin diseases since ancient times.
      Taking in to consideration the medicinal properties exhibited by this genus, it
      was decided to investigate the anti-cancer activity of CQ. Extracts obtained from
      CQ and their phenolic contents were subjected to in vitro evaluation of
      anticancer activity by using A431 (skin epidermoid carcinoma, human) cell line.
      The A431 cells were treated with different extracts of CQ in a dose dependent
      manner. Out of five extracts, the acetone extract demonstrated significant anti
      cancer activity in the A431 cell line. Hexane, chloroform, ethyl acetate and
      methanol extracts also exhibited cytotoxicity but to a comparatively lesser
      extent than the acetone extract. The GI(50) value of the acetone extract was
      found to be 8 MUg mL(-1), whereas GI(50) value of purified fraction of acetone
      extract, termed as AFCQ (active acetone fraction of CQ) with respect to A431
      cells, was found to be 4.8 MUg mL(-1). Furthermore, the mechanism of anticancer
      activity exhibited by AFCQ was investigated by comparing its effect with the
      standard anticancer drug Doxorubicin (DOX) by evaluating the status of apoptotic
      markers after treatment of A431 cells with AFCQ and DOX. Bax-Bcl-2 ratio along
      with the release of cytochrome c from mitochondria to cytoplasm, which is a
      hallmark of apoptosis, was also evaluated. Cleavage of PARP revealed that AFCQ
      induces apoptosis in A431 cells with reference to DOX.

PMID- 23175102
TI  - Mechanisms underlying the dualistic mode of action of major soy isoflavones in
      relation to cell proliferation and cancer risks.
AB  - Isoflavones are phytoestrogens that have been linked to both beneficial as well
      as adverse effects in relation to cell proliferation and cancer risks. The
      present article presents an overview of these seemingly contradicting health
      effects and of mechanisms that could be involved in this dualistic mode of
      action. One mechanism relates to the different ultimate cellular effects of
      activation of estrogen receptor (ER) alpha, promoting cell proliferation, and of
      ERbeta, promoting apoptosis, with the major soy isoflavones genistein and
      daidzein activating especially ERbeta. A second mode of action includes the role
      of epigenetics, including effects of isoflavones on DNA methylation, histone
      modification and miRNA expression patterns. The overview presented reveals that
      we are only at the start of unraveling the complex underlying mode of action for
      effects of isoflavones, both beneficial or adverse, on cell proliferation and
      cancer risks. It is evident that whatever model system will be applied, its
      relevance to human tissues with respect to ERalpha and ERbeta levels, co
      repressor and co-activator characteristics as well as its relevance to human
      exposure regimens, needs to be considered and defined.

PMID- 23175103
TI  - Structure sensitivity of CO oxidation on Co3O4: a DFT study.
AB  - The reaction mechanism of CO oxidation on the Co(3)O(4) (110) and Co(3)O(4) (111)
      surfaces is investigated by means of spin-polarized density functional theory
      (DFT) within the GGA+U framework. Adsorption situation and complete reaction
      cycles for CO oxidation are clarified. The results indicate that 1) the U value
      can affect the calculated energetic result significantly, not only the absolute
      adsorption energy but also the trend in adsorption energy; 2) CO can directly
      react with surface lattice oxygen atoms (O(2f)/O(3f)) to form CO(2) via the Mars
      van Krevelen reaction mechanism on both (110)-B and (111)-B; 3) pre-adsorbed
      molecular O(2) can enhance CO oxidation through the channel in which it directly
      reacts with molecular CO to form CO(2) [O(2)(a)+CO(g)->CO(2)(g)+O(a)] on (110)
      A/(111)-A; 4) CO oxidation is a structure-sensitive reaction, and the activation
      energy of CO oxidation follows the order of Co(3)O(4) (111)-A(0.78 eV)>Co(3)O(4)
      (111)-B (0.68 eV)>Co(3)O(4) (110)-A (0.51 eV)>Co(3)O(4) (110)-B (0.41 eV), that
      is, the (110) surface shows higher reactivity for CO oxidation than the (111)
      surface; 5) in addition to the O(2f), it was also found that Co(3+) is more
      active than Co(2+), so both O(2f) and Co(3+) control the catalytic activity of CO
      oxidation on Co(3)O(4), as opposed to a previous DFT study which concluded that
      either Co(3+) or O(2f) is the active site.

PMID- 23175104
TI  - A new linear model-based approach for inferences about the mean area under the
      curve.
AB  - Outcome versus time data are commonly encountered in biomedical and clinical
      research. A common strategy adopted in analyzing such longitudinal data is to
      condense the repeated measurements on each individual into a single summary
      statistic such as the area under the response versus time curve. Standard
      parametric or non-parametric methods are then applied to perform inferences on
      the conditional area under the curve distribution. Disadvantages of this approach
      include the disregard of the within-subject variation in the longitudinal
      profile. We propose a general linear model approach, accounting for the within
      subject variance, for estimation and hypothesis tests about the mean areas.
      Inferential properties of our approach are compared with those from standard
      methods of analysis using Monte Carlo simulation studies. The impact of missing
      data, within-subject heterogeneity and homogeneity of variance, are also
      evaluated. A real working example is used to illustrate the methodology. It is
      seen that the proposed approach is associated with a significant power advantage
      over traditional methods, especially when missing data are encountered.

PMID- 23175106
TI  - Ascorbate supplementation inhibits growth and metastasis of B16FO melanoma and
      4T1 breast cancer cells in vitamin C-deficient mice.
AB  - Degradation of the extracellular matrix (ECM) plays a critical role in the
      formation of tumors and metastasis and has been found to correlate with the
      aggressiveness of tumor growth and invasiveness of cancer. Ascorbic acid, which
      is known to be essential for the structural integrity of the intercellular
      matrix, is not produced by humans and must be obtained from the diet. Cancer
      patients have been shown to have very low reserves of ascorbic acid. Our main
      objective was to determine the effect of ascorbate supplementation on metastasis,
      tumor growth and tumor immunohistochemistry in mice unable to synthesize ascorbic
      acid [gulonolactone oxidase (gulo) knockout (KO)] when challenged with B16FO
      melanoma or 4T1 breast cancer cells. Gulo KO female mice 36-38 weeks of age were
      deprived of or maintained on ascorbate in food and water for 4 weeks prior to and
      2 weeks post intraperitoneal (IP) injection of 5x105 B16FO murine melanoma cells
      or to injection of 5x105 4T1 breast cancer cells into the mammary pad of mice.
      Ascorbate-supplemented gulo KO mice injected with B16FO melanoma cells
      demonstrated significant reduction (by 71%, p=0.005) in tumor metastasis compared
      to gulo KO mice on the control diet. The mean tumor weight in ascorbate
      supplemented mice injected with 4T1 cells was reduced by 28% compared to tumor
      weight in scorbutic mice. Scorbutic tumors demonstrated large dark cores,
      associated with increased necrotic areas and breaches to the tumor surface,
      apoptosis and matrix metalloproteinase-9 (MMP-9), and weak, disorganized or
      missing collagen I tumor capsule. In contrast, the ascorbate-supplemented group
      tumors had smaller fainter colored cores and confined areas of necrosis/apoptosis
      with no breaches from the core to the outside of the tumor and a robust collagen
      I tumor capsule. In both studies, ascorbate supplementation of gulo KO mice
      resulted in profoundly decreased serum inflammatory cytokine interleukin (IL)-6
      (99% decrease, p=0.01 in the B16F0 study and 85% decrease, p=0.08 in the 4T1
      study) compared to the levels in gulo KO mice deprived of ascorbate. In the B16FO
      study, ascorbate supplementation of gulo KO mice resulted in profoundly decreased
      serum VEGF (98% decrease, p=0.019 than in the scorbutic gulo KO mice). As
      expected, mean serum ascorbate level in ascorbate-restricted mice was 2%
      (p<0.001) of the mean ascorbate levels in supplemented mice. In conclusion,
      ascorbate supplementation hinders metastasis, tumor growth and inflammatory
      cytokine secretion as well as enhanced encapsulation of tumors elicited by
      melanoma and breast cancer cell challenge in gulo KO mice.

PMID- 23175107
TI  - Optimal surface marker locations for tumor motion estimation in lung cancer
      radiotherapy.
AB  - Using fiducial markers on the patient's body surface to predict the tumor
      location is a widely used approach in lung cancer radiotherapy. The purpose of
      this work is to propose an algorithm that automatically identifies a sparse set
      of locations on the patient's surface with the optimal prediction power for the
      tumor motion. In our algorithm, it is assumed that there is a linear relationship
      between the surface marker motion and the tumor motion. The sparse selection of
      markers on the external surface and the linear relationship between the marker
      motion and the internal tumor motion are represented by a prediction matrix. Such
      a matrix is determined by solving an optimization problem, where the objective
      function contains a sparsity term that penalizes the number of markers chosen on
      the patient's surface. Bregman iteration is used to solve the proposed
      optimization problem. The performance of our algorithm has been tested on
      realistic clinical data of four lung cancer patients. Thoracic 4DCT scans with
      ten phases are used for the study. On a reference phase, a grid of points are
      casted on the patient's surfaces (except for the patient's back) and propagated
      to other phases via deformable image registration of the corresponding CT images.
      Tumor locations at each phase are also manually delineated. We use nine out of
      ten phases of the 4DCT images to identify a small group of surface markers that
      are mostly correlated with the motion of the tumor and find the prediction matrix
      at the same time. The tenth phase is then used to test the accuracy of the
      prediction. It is found that on average six to seven surface markers are
      necessary to predict tumor locations with a 3D error of about 1 mm. It is also
      found that the selected marker locations lie closely in those areas where surface
      point motion has a large amplitude and a high correlation with the tumor motion.
      Our method can automatically select sparse locations on the patient's external
      surface and estimate a correlation matrix based on 4DCT, so that the selected
      surface locations can be used to place fiducial markers to optimally predict
      internal tumor motions.

PMID- 23175112
TI  - Glioma: Tumour cells in reverse.

PMID- 23175108
TI  - Metastasis: Converging targets.

PMID- 23175114
TI  - Metastasis: Elf represses snail.

PMID- 23175116
TI  - Signalling: New roles for TLR2.

PMID- 23175117
TI  - Tumour immunology: Context is key for TSLP.

PMID- 23175118
TI  - MicroRNAs: Editing changes the meaning.

PMID- 23175119
TI  - DNA repair dysregulation from cancer driver to therapeutic target.
AB  - Dysregulation of DNA damage repair and signalling to cell cycle checkpoints,
      known as the DNA damage response (DDR), is associated with a predisposition to
      cancer and affects responses to DNA-damaging anticancer therapy. Dysfunction of
      one DNA repair pathway may be compensated for by the function of another
      compensatory DDR pathway, which may be increased and contribute to resistance to
      DNA-damaging chemotherapy and radiotherapy. Therefore, DDR pathways make an ideal
      target for therapeutic intervention; first, to prevent or reverse therapy
      resistance; and second, using a synthetic lethal approach to specifically kill
      cancer cells that are dependent on a compensatory DNA repair pathway for survival
      in the context of cancer-associated oxidative and replicative stress. These
      hypotheses are currently being tested in the laboratory and are being translated
      into clinical studies.

PMID- 23175123
TI  - [Proverbial wisdom].

PMID- 23175121
TI  - The genetic basis of phenotypic heterogeneity in myelodysplastic syndromes.
AB  - Myelodysplastic syndromes (MDS) are malignant clonal disorders of haematopoietic
      stem cells and their microenvironment, affecting older individuals (median age
      ~70 years). Unique features that are associated with MDS - but which are not
      necessarily present in every patient with MDS - include excessive apoptosis in
      maturing clonal cells, a pro-inflammatory bone marrow microenvironment, specific
      chromosomal abnormalities, abnormal ribosomal protein biogenesis, the presence of
      uniparental disomy, and mutations affecting genes involved in proliferation,
      methylation and epigenetic modifications. Although emerging insights establish an
      association between molecular abnormalities and the phenotypic heterogeneity of
      MDS, their origin and progression remain enigmatic.

PMID- 23175120
TI  - Medulloblastomics: the end of the beginning.
AB  - The division of medulloblastoma into different subgroups by microarray expression
      profiling has dramatically changed our perspective of this malignant childhood
      brain tumour. Now, the availability of next-generation sequencing and
      complementary high-density genomic technologies has unmasked novel driver
      mutations in each medulloblastoma subgroup. The implications of these findings
      for the management of patients are readily apparent, pinpointing previously
      unappreciated diagnostic and therapeutic targets. In this Review, we summarize
      the 'explosion' of data emerging from the application of modern genomics to
      medulloblastoma, and in particular the recurrent targets of mutation in
      medulloblastoma subgroups. These data are currently making their way into
      clinical trials as we seek to integrate conventional and molecularly targeted
      therapies.

PMID- 23175124
TI  - [Parents with cancer and their minor children--a nationwide survey of outpatient
      psychosocial cancer counselling service regarding needs and its utilisation].
AB  - OBJECTIVES: Children of cancer patients have an increased risk for developing
      emotional problems. While psychosocial cancer counselling services are available
      all over the country, it is unclear if parents seek for help and if specific
      approaches for families are offered. METHODS: A survey was made of outpatient
      cancer counselling services in Germany (n=228). The response rate was 56%.
      Descriptive and content analyses of the data have been used. RESULTS: Providers
      estimate that 55% of their patients are between 18 and 55 years with 18% of them
      having minor children. However, only 53% do regularly ask their patients if they
      have minor children. Family- or child-settings are not provided regularly. Over
      60% of providers would welcome special courses on this subject. CONCLUSION:
      Although psychosocial care of minor children is mentioned in outpatient
      psychosocial cancer counselling guidelines, children are not included regularly.
      A stronger emphasis on this topic in further education has to be made.

PMID- 23175122
TI  - Human tumour viruses and the deregulation of cell polarity in cancer.
AB  - The role of cell polarity regulators in the development of cancer has long been
      an enigma. Despite displaying characteristics of tumour suppressors, the core
      regulators of polarity are rarely mutated in tumours and there are few data from
      animal models to suggest that they directly contribute to cancer susceptibility,
      thus questioning their relevance to human carcinogenesis. However, a body of data
      from human tumour viruses is now providing compelling evidence of a central role
      for the perturbation of cell polarity in the development of cancer.

PMID- 23175125
TI  - [Situation and perspectives of public health in Germany--research and teaching.
      Position paper of the German Public Health Association].
AB  - This position paper of the German Public Health Association describes current
      situation and perspectives of public health in Germany with emphasis on research
      and teaching. It outlines those measures necessary for strengthening of public
      health research in Germany.

PMID- 23175127
TI  - A novel GATA5 loss-of-function mutation underlies lone atrial fibrillation.
AB  - Atrial fibrillation (AF), the most common sustained cardiac arrhythmia, is
      associated with significantly increased morbidity and mortality. Cumulative
      evidence highlights the importance of genetic defects in the pathogenesis of AF.
      However, AF is of remarkable heterogeneity and the genetic determinants of AF in
      a vast majority of patients remain illusive. In this study, the coding exons and
      splice junctions of the GATA5 gene, which encodes a zinc-finger transcription
      factor essential for normal cardiogenesis, were sequenced in 118 unrelated
      patients with lone AF. The available relatives of the index patient carrying an
      identified mutation and 200 unrelated ethnically-matched healthy individuals used
      as controls were genotyped. The functional effect of the mutant GATA5 was
      characterized in contrast to its wild-type counterpart using a luciferase
      reporter assay system. As a result, a novel heterozygous GATA5 mutation, p.W200G,
      was identified in a family with AF inherited as an autosomal dominant trait. The
      mutation was absent in 200 control individuals and the altered amino acid was
      completely conserved evolutionarily across species. Functional analysis showed
      that the mutation of GATA5 was associated with a significantly decreased
      transcriptional activity. These findings provide novel insight into the molecular
      mechanism involved in AF, suggesting potential implications for the early
      prophylaxis and gene-specific therapy of AF.

PMID- 23175128
TI  - Radial artery damage due to sheath fracture: unpredicted complication.

PMID- 23175129
TI  - FDG-PET/CT in the diagnosis of aortitis in fever of unknown origin with severe
      aortic incompetence.

PMID- 23175130
TI  - Statement on matching language to the type of evidence used in describing
      outcomes data.

PMID- 23175131
TI  - Thalassaemia major and the heart: a toxic cardiomyopathy tamed?

PMID- 23175132
TI  - Screening of competitive athletes to prevent sudden death: Think twice.

PMID- 23175133
TI  - Ajuvent interventional techniques for the treatment of intra-coronary thrombus.

PMID- 23175134
TI  - Nanotoxicity assessment of quantum dots: from cellular to primate studies.
AB  - Tremendous research efforts have been devoted to fabricating high quality quantum
      dots (QDs) for applications in biology and medicine. Much of this research was
      pursued with an ultimate goal of using QDs in clinical applications. However, a
      great deal of concern has been voiced about the potential hazards of QDs due to
      their heavy-metal content. Many studies have demonstrated toxicity of various QDs
      in cell culture studies. However, in a smaller number of studies using small
      animal models (mice and rats), no abnormal behaviour or tissue damage was noticed
      over periods of months after the systemic administration of QDs. Nevertheless,
      the correlation of these results with the potential for negative effects of QD on
      humans remains unclear. Many urgent questions must be answered before the QDs
      community moves into the clinical research phase. This review provides an
      overview of the toxicity assessment of QDs, ranging from cell culture studies to
      animal models and discusses their findings. Guidelines for using various nonhuman
      primate models for QD toxicity studies are highlighted. This review article is
      intended to promote the awareness of current developments of QD applications in
      biology, the potential toxicity of QDs, and approaches to minimizing toxicity.

PMID- 23175135
TI  - Direct amide formation using radiofrequency heating.
AB  - We present a simple method for direct and solvent-free formation of amides from
      carboxylic acids and amines using radiofrequency heating. The direct energy
      coupling of the AC magnetic field via nickel ferrite magnetic nanoparticles
      enables fast and controllable heating, as well as enabling facile work-up via
      magnetic separation.

PMID- 23175136
TI  - Association between noninvasive fibrosis markers and mortality among adults with
      nonalcoholic fatty liver disease in the United States.
AB  - The clinical and public health significance of nonalcoholic fatty liver disease
      (NAFLD) is not well established. We investigated the long-term effect of NAFLD on
      mortality. This analysis utilized the National Health and Nutrition Examination
      Survey conducted in 1988-1994 and subsequent follow-up data for mortality through
      December 31, 2006. NAFLD was defined by ultrasonographic detection of hepatic
      steatosis in the absence of other known liver diseases. The presence and severity
      of hepatic fibrosis in subjects with NAFLD was determined by the NAFLD fibrosis
      score (NFS), the aspartate aminotransferase to platelet ratio index (APRI), and
      FIB-4 score. Of 11,154 participants, 34.0% had NAFLD--the majority (71.7%) had
      NFS consistent with lack of significant fibrosis (NFS <-1.455), whereas 3.2% had
      a score indicative of advanced fibrosis (NFS >0.676). After a median follow-up of
      14.5 years, NAFLD was not associated with higher mortality (age- and sex-adjusted
      hazard ratio [HR]: 1.05; 95% confidence interval [CI]: 0.93-1.19). In contrast,
      there was a progressive increase in mortality with advancing fibrosis scores.
      Compared to subjects without fibrosis, those with a high probability of advanced
      fibrosis had a 69% increase in mortality (for NFS: HR, 1.69, 95% CI: 1.09-2.63;
      for APRI: HR, 1.85, 95% CI: 1.02-3.37; for FIB-4: HR, 1.66, 95% CI: 0.98-2.82)
      after adjustment for other known predictors of mortality. These increases in
      mortality were almost entirely from cardiovascular causes (for NFS: HR, 3.46, 95%
      CI: 1.91-6.25; for APRI: HR, 2.53, 95% CI: 1.33-4.83; for FIB-4: HR, 2.68, 95%
      CI: 1.44-4.99). CONCLUSIONS: Ultrasonography-diagnosed NAFLD is not associated
      with increased mortality. However, advanced fibrosis, as determined by
      noninvasive fibrosis marker panels, is a significant predictor of mortality,
      mainly from cardiovascular causes, independent of other known factors.

PMID- 23175137
TI  - Lamellar ichthyosis with genu valgum: unfolding the link.
AB  - We describe a case of lamellar ichthyosis with bilateral genu valgum. The
      association of genu valgum with congenital ichthyosis is rare. Our patient, a 22
      year-old girl, had lamellar ichthyosis and was born with a collodion membrane.
      She developed progressive valgus deformity of the knees of 5 years duration
      associated with difficulty in walking. On evaluation, she had generalised scaly
      skin lesions along with bilateral genu valgum and biochemical evidence of vitamin
      D deficiency. Skin serves as an important site for vitamin D synthesis and thus
      skeletal deformities secondary to vitamin D deficiency may occur in cases of
      congenital ichthyosis, causing a diagnostic dilemma due to the unusual
      association. This case serves as a reminder that clinicians need to be aware of
      such an association in order to prevent, appropriately diagnose and adequately
      treat the rare case of congenital ichthyosis with rickets and osteomalacia.

PMID- 23175138
TI  - Photostability of a dyad of magnesium porphyrin and fullerene and its application
      to photocurrent conversion.
AB  - A new type of acceptor-donor(2) dyad system containing two magnesium porphyrin
      molecules and a fullerene molecule is much more stable than the magnesium
      porphyrin itself. When it is fabricated into a binary system using imidazole
      carboxylic acid as a linker to indium tin oxide, the molecule effects efficient
      photocurrent generation that surpasses the device using the corresponding zinc
      porphyrin.

PMID- 23175139
TI  - Age at menarche and risk of ovarian cancer: a meta-analysis of epidemiological
      studies.
AB  - Epidemiological studies have reported inconsistent associations between
      menarcheal age and ovarian cancer risk. To our knowledge, a meta-analysis for the
      association between menarcheal age and ovarian cancer has not been reported.
      Relevant published studies of menarcheal age and ovarian cancer were identified
      using MEDLINE, EMBASE and Web of Science through the end of April 2012. Two
      authors (T-T.G. and Q-J.W.) independently assessed eligibility and extracted
      data. We pooled the relative risks (RRs) from individual studies using a random
      effects model and performed heterogeneity and publication bias analyses. A total
      of 27 observational studies consisting of 22 case-control and five cohort studies
      were included in our analysis. In a pooled analysis of all studies, a
      statistically significant inverse association was observed between menarcheal age
      (for the oldest compared to the youngest category) and ovarian cancer risk (RR =
      0.85; 95% confidence interval [CI] = 0.75-0.97). The pooled RRs of ovarian cancer
      for the oldest versus the youngest categories of menarcheal age in prospective
      and case-control studies were 0.89 (95% CI = 0.76-1.03) and 0.84 (95% CI = 0.70
      0.99), respectively. Inverse associations between menarcheal age and ovarian
      cancer risk were observed in most subgroups; however, the significant association
      was restricted to invasive and borderline serous ovarian cancer. In conclusion,
      findings from this meta-analysis support that menarcheal age was inversely
      associated with the risk of ovarian cancer. More large studies are warranted to
      stratify these results by different cancer grading and histotype of ovarian
      cancer.

PMID- 23175140
TI  - Comparison of lipid sinks in sequestering common intoxicating drugs.
AB  - Intravenous lipid emulsion is a recommended treatment for local anesthetic
      intoxication. The lipid sink theory hypothesizes that the mechanism behind the
      lipid treatment is the entrapment of toxic drugs in plasma, preventing them from
      reaching target receptors. Lipid sink treatment has also been used as a last
      refuge treatment for severe tricyclic antidepressant intoxication with seemingly
      beneficial results. We selected three drugs, i.e. amiodarone, ketamine, and
      amitriptyline, that can cause severe intoxication and compared their interactions
      with two commercial fat emulsions (Intralipid(r) and ClinOleic(r)) and one
      synthetic liposome (80:20 mol% phosphatidylcholine/phosphatidylglycerol)
      dispersion. The interaction studies were carried out by capillary electrokinetic
      chromatography and the retention factors and distributions constants of the drugs
      were calculated. The results demonstrate that there is stronger interaction
      between the drugs and the synthetic liposome dispersion than with the commercial
      emulsions.

PMID- 23175141
TI  - Validation and scale-up of plasmid DNA purification by phenyl-boronic acid
      chromatography.
AB  - This study addresses the feasibility of scaling-up the removal of host cell
      impurities from plasmid DNA (pDNA)-containing Escherichia coli lysates by phenyl
      boronic (PB) acid chromatography using columns packed with 7.6 and 15.2 cm(3) of
      controlled porous glass beads (CPG) derivatized with PB ligands. Equilibration
      was performed with water at 10 cm(3) /min and no conditioning of the lysate feed
      was required. At a ratio of lysate feed to adsorbent volume of 1.3, 93-96% of
      pDNA was recovered in the flow through while 66-71% of impurities remained bound
      (~2.5-fold purification). The entire sequence of loading, washing, elution, and
      re-equilibration was completed in 20 min. Run-to-run consistency was observed in
      terms of chromatogram features and performance (yield, purification factor,
      agarose electrophoresis) across the different amounts of adsorbent (0.75-15.2
      cm(3) ) by performing successive injections of lysates prepared independently and
      containing 3.7 or 6.1 kbp plasmids. The column productivity at large scale was 4
      dm(3) of alkaline lysate per hour per dm(3) of PB-CPG resin. The method is rapid,
      reproducible, simple, and straightforward to scale-up. Furthermore, it is capable
      of handling heavily contaminated samples, constituting a good alternative to
      purification techniques such as isopropanol precipitation, aqueous two-phase
      systems, and tangential flow filtration.

PMID- 23175142
TI  - Toward reading the sequence of short oligonucleotides from their retention
      factors obtained by means of hydrophilic interaction chromatography and ion
      interaction reversed-phase liquid chromatography.
AB  - Retention characteristics of selected synthetic 5'-terminal phosphate absent
      penta-nucleotides containing adenine, guanine, and thymine were studied in
      relation to their sequence by hydrophilic interaction chromatography and ion
      interaction reversed-phase liquid chromatography. The organic solvent content,
      pH, and buffer concentration in mobile phases were evaluated as influential
      separation conditions. Data demonstrate that both compared chromatographic modes
      can be used to separate synthetic penta-nucleotides according to their nucleotide
      composition. Moreover, reversed-phase liquid chromatography allows separation
      according to their sequence. We have found a simple linear additive model to
      describe the retention order in both separation modes in regard to their
      sequence. In hydrophilic interaction chromatography, the retention behavior is
      controlled primarily by the hydrophilicity of involved nucleotides and minimally
      by their sequence position. For reversed-phase liquid chromatography, the
      nucleotide hydrophobicity plays an important role in their retention properties
      and the influence of their location in sequence on the retention increases toward
      the center and decreases toward the termini. Our results show that the penta
      nucleotide sequence, and thus its spatial arrangement induced by the surrounding
      environment, is highly related to the retention properties, so it may be
      hypothetically used to read the sequence from the retention properties acquired
      under particular separation conditions.

PMID- 23175143
TI  - Separation science: enabling technology in biotech.

PMID- 23175146
TI  - Application of short-end injection procedure in CE.
AB  - CE is well known for its many advantages, including the speed of the analyses;
      most of which can be accomplished in less than 10 min. However many potential
      fields of application such as pharmaceutical research and industry and clinical
      diagnostics require analyses of large numbers of samples and so need an even
      shorter analysis time to be practical. There are generally three main options for
      enhancing the throughput of electromigration methods - using microchip or multi
      capillary systems or modifying the method preformed on single capillary
      instruments. The latter option will probably be the method of choice for most
      laboratories, since they are only equipped with classical commercial CE
      instrumentation. Although several approaches can be used - higher electric field,
      EOF modification, external pressure application during analysis, this article
      reviews one of the simplest and at the same time most used, the so-called short
      end injection procedure.

PMID- 23175147
TI  - Evaluation of survival benefits by platinums and taxanes for an unfavourable
      subset of carcinoma of unknown primary: a systematic review and meta-analysis.
AB  - BACKGROUND: Although chemotherapeutic regimens containing a taxane or platinum
      agent have been widely recommended for unfavourable carcinoma of unknown primary
      (CUP), no evidence exists for the superiority of any administered regimens. To
      date, the efficacy has been mostly assessed in the limited setting of phase II
      trials, and few attempts have been made to synthesise all available data for
      survival outcomes. METHODS: Electronic databases were searched from 1980 to 2011.
      Survival results were combined for each pre-specified category of regimens using
      a random-effects model, and meta-regression models were used to adjust for
      heterogeneity in some known prognostic factors. RESULTS: A total of 32 studies
      were included for meta-analysis. Tendency towards better survival outcome by
      platinums or taxanes was indicated. After adjustment for important prognostic
      factors, however, the difference between the platinum-based and non-platinum
      regimens became no longer significant. Survival benefits by the taxane-based
      regimens remained significant, with a prolonged median survival time of 1.52
      months (P=0.03) and a higher 1-year survival rate of 6.25% (P=0.05), but the
      benefit did not sustain for 2 years. CONCLUSION: Although no effective therapies
      have been established, this meta-analysis helps to fill an important gap of
      evidence. However, caution should still be taken because of the potential
      unmeasured confounding.

PMID- 23175148
TI  - Communication about colorectal cancer screening in Britain: public preferences
      for an expert recommendation.
AB  - BACKGROUND: Informed decision-making approaches to cancer screening emphasise the
      importance of decisions being determined by individuals' own values and
      preferences. However, advice from a trusted source may also contribute to
      autonomous decision-making. This study examined preferences regarding a
      recommendation from the NHS and information provision in the context of
      colorectal cancer (CRC) screening. METHODS: In face-to-face interviews, a
      population-based sample of adults across Britain (n=1964; age 50-80 years)
      indicated their preference between: (1) a strong recommendation to participate in
      CRC screening, (2) a recommendation alongside advice to make an individual
      decision, and (3) no recommendation but advice to make an individual decision.
      Other measures included trust in the NHS and preferences for information on
      benefits and risks. RESULTS: Most respondents (84%) preferred a recommendation
      (47% strong recommendation, 37% recommendation plus individual decision-making
      advice), but the majority also wanted full information on risks (77%) and
      benefits (78%). Men were more in favour of a recommendation than women (86% vs
      81%). Trust in the NHS was high overall, but the minority who expressed low trust
      were less likely to want a recommendation. CONCLUSION: Most British adults want
      full information on risks and benefits of screening but they also want a
      recommendation from an authoritative source. An 'expert' view may be an important
      part of autonomous health decision-making.

PMID- 23175150
TI  - KRAS mutational status affects oxaliplatin-based chemotherapy independently from
      basal mRNA ERCC-1 expression in metastatic colorectal cancer patients.
AB  - BACKGROUND: In this study, we evaluated the possibility that KRAS mutational
      status might be predictive of oxaliplatin (OXA) efficacy. We also explored the
      role of excision repair cross complementing group-1 (ERCC-1). METHODS: Ninety
      anti-epidermal growth factor receptor-naive advanced colorectal cancer patients
      were retrospectively analysed. In all patients KRAS mutational status was
      assessed. In 60 patients mRNA ERCC-1 expression was also investigated. Response
      rate (RR) and progression-free survival (PFS) after FOLFOX-6+/-bevacizumab were
      evaluated according to KRAS status and mRNA ERCC-1 expression. RESULTS: Among 90
      patients 47% wild-type (wt) and 53% mutated (mt) KRAS tumours were found.
      Response rate was 26% in the wt KRAS group, whereas it was 56% in the mt KRAS
      group; the difference is statistically significant in the total sample (P=0.008)
      and when only patients receiving FOLFOX-6+/-bevacizumab as first-line are
      considered (P=0.01). Progression-free survival was longer in mt than in wt KRAS
      patients over all patients (10 vs 8 months, respectively, P=0.001) and in those
      treated as first-line (10 vs 8 months, respectively, P=0.0069). Mt KRAS patients
      experienced a longer survival (24 vs 18 months; P=0.01). ERCC-1 mRNA expression
      was not found to correlate with FOLFOX activity in our analysis. CONCLUSION: Our
      results suggest that activating mutation of KRAS oncogene may predict response to
      OXA. Basal expression of ERCC-1 mRNA does not explain the high efficacy of FOLFOX
      6 in mt KRAS patients.

PMID- 23175149
TI  - Brain-derived neurotrophic factor/tropomyosin-related kinase B pathway in gastric
      cancer.
AB  - BACKGROUND: Brain-derived neutrophic factor (BDNF) is a member of the neutrophin
      family that is known to activate the high-affinity tropomyosin-related receptor
      kinase B (TrkB). This study aimed to clarify the clinical and biological
      significance of the BDNF/TrkB pathway in gastric cancer. METHODS: We analysed
      BDNF and TrkB expression in gastric cancer samples by real-time reverse
      transcription PCR and immunohistochemistry. To investigate the biological role of
      BDNF/TrkB axis, recombinant human BDNF (rhBDNF) and the Trk antagonist K252a were
      used for in vitro and in vivo analysis. RESULTS: The BDNF expression at the
      invasive front of primary tumours was significantly elevated compared with that
      in the tumour core and adjacent normal mucosa. Increased BDNF expression at the
      invasive front was significantly correlated with factors reflecting disease
      progression, and poor prognosis. Increased co-expression of the BDNF/TrkB axis
      was significantly correlated with poor prognosis. Gastric cancer cells expressed
      BDNF, and administration of rhBDNF promoted proliferation, migration, invasion,
      and inhibition of anoikis. These effects were generally inhibited by K252a. In an
      in vivo assay, BDNF(+)/TrkB(+) gastric cancer cells injected into nude mice
      established peritoneal dissemination, whereas K252a inhibited tumour growth.
      CONCLUSION: The BDNF/TrkB pathway might be deeply involved in gastric cancer
      disease progression.

PMID- 23175151
TI  - MicroRNA profiling of peripheral nerve sheath tumours identifies miR-29c as a
      tumour suppressor gene involved in tumour progression.
AB  - BACKGROUND: Neurofibromatosis type 1 is one of the most common familial diseases,
      the hallmark of which is the development of multiple neurofibromas. These are
      benign nerve sheath tumours, which can transform into malignant peripheral nerve
      sheath tumours (MPNST). METHODS: The aim of this study was to identify
      differentially expressed microRNA (miRNA) in neurofibromas and MPNST obtained
      from patients with neurofibromatosis type 1 using microarray analysis.
      Differential expression was validated by reverse transcription quantitative-PCR,
      and functional studies were performed after transfection of miRNA oligonucleotide
      mimics into MPNST cells. RESULTS: Sixteen miRNA were significantly differentially
      expressed in MPNST compared with NF, and of these fourteen were downregulated in
      MPNST: these included miR-30e*, miR-29c*, miR-29c, miR-340*, miR-30c, miR-139-5p,
      miR-195, miR-151-5p, miR-342-5p, miR-146a, miR-150, miR-223, let-7 a and let-7 g
      with a false discovery rate of q=8.48E-03 for the least significant miRNA. In
      contrast, miR-210 and miR-339-5p were upregulated in MPNST compared with
      neurofibromas. Prediction softwares/algorithms identified a list of genes
      targeted by miR-29c including extracellular matrix genes and matrix
      metalloproteinase (MMP)-2, all of which are reported to be involved in cell
      migration and invasion. Functional studies in a MPNST cell line, sNF96.2, using a
      mimic of the mature miR-29c showed reduced invasion, whereas there was no change
      in proliferation. Zymography of the manipulated cells showed that MMP2 activity
      was also reduced when miR-29c expression was forced in sNF96.2. CONCLUSION: We
      provide evidence that reduction of miR-29c has a pivotal role in the progression
      of nerve sheath tumours and results by increasing the invasive/migratory
      properties of nerve sheath tumours.

PMID- 23175152
TI  - The mechanism of long-term low-dose asymmetric dimethylarginine inducing
      transforming growth factor-beta expression in endothelial cells.
AB  - Asymmetric dimethylarginine (ADMA), an endogenous nitric oxide synthase (NOS)
      inhibitor, accumulates in plasma during chronic kidney disease (CKD). High plasma
      levels of ADMA can increase transforming growth factor-beta (TGF-beta)
      expression, related to renal fibrosis, but the precise molecular mechanism is not
      explicit. The present study was designed to determine the mechanism through which
      long-term low-dose ADMA induces TGF-beta expression in endothelial cells and to
      investigate the molecular mechanism of its action. Human umbilical vein
      endothelial cells (HUVECs) were exposed to low-dose ADMA (5 and 10 umol/l) for 7
      passages and TGF-beta expression was determined. Human renal glomerular
      endothelial cells (HRGECs) were exposed to high-dose ADMA (100 umol/l) which were
      used to clarify the molecular mechanism. The results showed that long-term low
      dose ADMA (5 and 10 umol/l) increases TGF-beta production in both mRNA and
      protein levels in HUVECs in a time-dependent manner. We confirmed that exogenous
      ADMA (100 umol/l) significantly enhanced stress fiber formation in HRGECs and
      upregulated TGF-beta expression. Such effects of ADMA in HRGECs were inhibited by
      pre-treatment with actin depolymerizing agent, actin stabilizing agent, p38 MAPK
      inhibitor and NADPH oxidase inhibitor. In addition, we demonstrated that ADMA
      (100 umol/l) significantly activated nuclear factor-kappaB (NF-kappaB) in HRGECs,
      which was markedly attenuated by actin depolymerizing agent, actin stabilizing
      agent, p38 MAPK inhibitor and NADPH oxidase inhibitor. In brief, the present
      study demonstrated that long-term low-dose ADMA induces TGF-beta expression in
      endothelial cells at both the gene and protein levels. The actin cytoskeleton may
      be involved in modulation of ADMA-induced NF-kappaB activation and the ensuing
      TGF-beta expression in HRGECs.

PMID- 23175153
TI  - SSEA-3 as a novel amplifying cancer cell surface marker in colorectal cancers.
AB  - Findings from studies on stem cells have been applied to cancer stem cell (CSC)
      research, but little is known about the relationship between ES cell-related cell
      surface markers and CSCs. In this study, we focused on stage-specific embryonic
      antigen 3 (SSEA-3), a marker of mesenchymal stem cells and Muse cells in
      colorectal cancer (CRC). Expression of SSEA-3 in human CRC cell lines and
      clinical specimens, specifically the relationship of SSEA-3 expression and the
      representative CSC markers (CD44, CD166, ALDH, CD24 and CD26) as well as with
      mesenchymal stem cell/Muse cell marker (CD105) were assessed. To characterize
      SSEA-3-expressing cells, tumorigenicity, sphere formation ability, expression of
      iPS genes (Oct4, NANOG, SOX2 and c-Myc), cell proliferation and cell cycle status
      were assessed. SSEA-3 expression was identified in Caco-2, DLD-1, HT-29, SW480
      and HCT116, but not in CaR-1 cells. No significant relationship between SSEA-3
      and other stem cell markers was detected. SSEA-3+ cells showed increased
      tumorigenicity in vivo, but lower sphere formation ability in vitro than SSEA-3-.
      iPS gene expression was not correlated with SSEA-3 expression status. SSEA-3+
      cells showed higher proliferative ability than SSEA-3- through enhanced cell
      cycles by decreased expression of p21Cip1/Waf1 and p27Kip1. Immunofluorescence
      analysis in clinical specimens indicated that expression of SSEA-3 is limited to
      stromal cells in normal mucosa but broad in poorly differentiated adenocarcinoma.
      These observations indicated that SSEA-3+ cells in CRC have immature phenotype
      but decreased self-renewal ability and may function as tumor transient amplifying
      cells or delayed contributing tumor-initiating cells.

PMID- 23175154
TI  - Large remanent polarization and small leakage in sol-gel derived
      Bi(Zn(1/2)Zr(1/2))O3-PbTiO3 ferroelectric thin films.
AB  - The applications of ferroelectric thin films such as the sensitivity of
      nonvolatile ferroelectric random access memories are closely linked with large
      remnant polarization. The high-T(C) (1-x)Bi(Zn(1/2)Zr(1/2))O(3)-xPbTiO(3) (x =
      0.7-0.9) thin films with high (100) orientation were fabricated on
      Pt(111)/Ti/SiO(2)/Si substrates via a sol-gel method. The thin films could be
      crystallized well in a phase-pure perovskite structure. The electrical properties
      of the sol-gel-derived BZZ-PT thin films were investigated. A large remanent
      polarization with 2P(r) up to 110 MUC cm(-2) and a small leakage current of 3.8 *
      10(-7) A cm(-2) under an electric field of 150 kV cm(-1) are observed on the
      0.2BZZ-0.8PT thin films. Furthermore, a relatively stable polarization fatigue
      property was achieved, indicating a potential application in high-temperature
      ferroelectric devices.

PMID- 23175155
TI  - Arsenic-induced biochemical and genotoxic effects and distribution in tissues of
      Sprague-Dawley rats.
AB  - Arsenic (As) is a well documented human carcinogen. However, its mechanisms of
      toxic action and carcinogenic potential in animals have not been conclusive. In
      this research, we investigated the biochemical and genotoxic effects of As and
      studied its distribution in selected tissues of Sprague-Dawley rats. Four groups
      of six male rats, each weighing approximately 60 +/- 2 g, were injected
      intraperitoneally, once a day for 5 days with doses of 5, 10, 15, 20 mg/kg bw of
      arsenic trioxide. A control group was also made of 6 animals injected with
      distilled water. Following anaesthetization, blood was collected and enzyme
      analysis was performed by spectrophotometry following standard protocols. At the
      end of experimentation, the animals were sacrificed, and the lung, liver, brain
      and kidney were collected 24 h after the fifth day treatment. Chromosome and
      micronuclei preparation was obtained from bone marrow cells. Arsenic exposure
      significantly increased (p<0.05) the activities of plasma alanine
      aminotransferase-glutamate pyruvate transaminase (ALT/GPT), and aspartate
      aminotransferase-glutamate oxaloacetate transaminase (AST/GOT), as well as the
      number of structural chromosomal aberrations (SCA) and frequency of micronuclei
      (MN) in the bone marrow cells. In contrast, the mitotic index in these cells was
      significantly reduced (p<0.05). These findings indicate that aminotransferases
      are candidate biomarkers for arsenic-induced hepatotoxicity. Our results also
      demonstrate that As has a strong genotoxic potential, as measured by the bone
      marrow SCA and MN tests in Sprague-Dawley rats. Total arsenic concentrations in
      tissues were measured by inductively coupled plasma mass spectrometry (ICP-MS). A
      dynamic reaction cell (DRC) with hydrogen gas was used to eliminate the ArCl
      interference at mass 75, in the measurement of total As. Total As doses in
      tissues tended to correlate with specific exposure levels.

PMID- 23175156
TI  - Blueberry juice causes potent relaxation of rat aortic rings via the activation
      of potassium channels and the H2S pathway.
AB  - The objective of this study was to investigate the in vitro effects of blueberry
      juice on healthy rat aortic rings, and to explore the roles of potassium channels
      and of the hydrogen sulphide (H(2)S) pathway in mediating the effects of
      blueberry juice. Firstly, the antioxidant capacity of blueberry juice was
      compared to other popular juice drinks using the Folin-Ciocalteu and the DPPH
      assays. Blueberry juice had significantly higher total polyphenol content than
      any of the other drinks studied (p < 0.01). The effect of blueberry juice on
      noradrenaline-contracted aortic rings was then observed, and the juice caused
      significant inhibition of noradrenaline-induced contractions (p < 0.01). Voltage
      gated potassium channel (Kv) blockers 4-aminopyridine (1 mM) and 3,4
      diaminopyridine (1 mM), as well as the cystathionine gamma-lysase (CSE) inhibitor
      d,l-propargylglycine (2 mM) were then utilised to elucidate the role of Kv
      channels and the CSE/H(2)S pathway. Kv channel blocker 3,4-diaminopyridine caused
      significant blockade at 1/100 and 1/50 dilutions of juice (p < 0.01), whilst 4
      aminopyridine caused significant blockade of the 1/100 dilution of blueberry
      juice (p < 0.05). In addition, d,l-propargylglycine potently inhibited the effect
      of 1/100 and 1/50 dilutions of blueberry juice (p < 0.01). This study indicates
      that blueberry juice has potent vasorelaxing properties, and thus may be a useful
      dietary agent for the prevention and treatment of hypertension. This study also
      provides strong evidence that Kv channels and the CSE/H(2)S pathway may be
      responsible, at least in part, for mediating the effects of blueberry juice.

PMID- 23175157
TI  - Stable and recyclable Au25 clusters for the reduction of 4-nitrophenol.
AB  - Thiol-stabilized Au(25)L(18) monolayer protected clusters (MPCs) were found to be
      active for the reduction of 4-nitrophenol. Results suggest that these MPCs are
      stable catalysts and do not lose their structural integrity during the catalytic
      process. High stability under the reaction conditions enables the recyclability
      of these MPCs.

PMID- 23175158
TI  - Unequal allocation and allocation concealment.

PMID- 23175161
TI  - Two-stage randomized trials: outstanding issues.

PMID- 23175163
TI  - Metabolic viability of Escherichia coli trapped by dielectrophoresis in
      microfluidics.
AB  - The spatial and temporal control of biological species is essential in complex
      microfluidic biosystems. In addition, if the biological species is a cell,
      microfluidic handling must ensure that the cell's metabolic viability is
      maintained. The use of DEP for cell manipulation in microfluidics has many
      advantages because it is remote and fast, and the voltages required for cell
      trapping scale well with miniaturization. In this paper, the conditions for
      bacterial cell (Escherichia coli) trapping using a quadrupole electrode
      configuration in a PDMS microfluidic channel were developed both for stagnant and
      for in-flow fluidic situations. The effect of the electrical conductivity of the
      fluid, the applied electric field and frequency, and the fluid-flow velocity were
      studied. A dynamic exchange between captured and free-flowing cells during DEP
      trapping was demonstrated. The metabolic activity of trapped cells was confirmed
      by using E. coli cells genetically engineered to express green fluorescent
      protein under the control of an inducible promoter. Noninduced cells trapped by
      negative DEP and positive DEP were able to express green fluorescent protein
      minutes after the inducer was inserted in the microchannel system immediately
      after DEP trapping. Longer times of trapping prior to exposure to the inducer
      indicated first a degradation of the cell metabolic activity and finally cell
      death.

PMID- 23175164
TI  - [Evaluation of intra-organisational effects after use of certification programmes
      in hospital].
AB  - AIM: The introduction of quality management systems might be promoted by use of
      recognised certification programmes. Over the years, in health care organisations
      the certification model named KTQ has gained more and more importance. The aim of
      this study is to evaluate intra-organisational effects in a clinic after
      introduction of quality management on the basis of KTQ. METHODS: The evaluation
      was performed using a 2-step approach: first, before starting the implementation
      process of KTQ in the year 2008, and second, after the implementation process had
      become successful. Data were obtained by a systematic questionnaire survey.
      Hospital staff (physicians, nurses, and others like administration staff,
      technical and medical assistants) were asked to appraise the quality management,
      to give own preferences, and rate their overall satisfaction with the process.
      RESULTS: Response rates were 56% in the year 2008 and 50% in the year 2010.
      Subjects regarding the working atmosphere, leading of superiors, organisational
      issues, and pervasion of quality management predominantly were found to be
      improved, almost with high statistical significance. At the same time, higher
      satisfaction values could be determined. CONCLUSIONS: There might be high
      acceptance to the undergone changes from the staff members' point of view. It
      appears that the implementation process has led to higher satisfaction values.
      Moreover it can be concluded that certification programmes might be able to
      promote the needed pervasion of quality management throughout the institution.

PMID- 23175165
TI  - Manifold-based feature point matching for multi-modal image registration.
AB  - BACKGROUND: Images captured using different modalities usually have significant
      variations in their intensities, which makes it difficult to reveal their
      internal structural similarities and achieve accurate registration. Most
      conventional feature-based image registration techniques are fast and efficient,
      but they cannot be used directly for the registration of multi-modal images
      because of these intensity variations. METHODS: This paper introduces the theory
      of manifold learning to transform the original images into mono-modal modalities,
      which is a feature-based method that is applicable to multi-modal image
      registration. Subsequently, scale-invariant feature transform is used to detect
      highly distinctive local descriptors and matches between corresponding images,
      and a point-based registration is executed. RESULTS: The algorithm was tested
      with T1- and T2-weighted magnetic resonance (MR) images obtained from BrainWeb.
      Both qualitative and quantitative evaluations of the method were performed and
      the results compared with those produced previously. The experiments showed that
      feature point matching after manifold learning achieved more accurate results
      than did the similarity measure for multi-modal image registration. CONCLUSIONS:
      This study provides a new manifold-based feature point matching method for multi
      modal medical image registration, especially for MR images. The proposed method
      performs better than do conventional intensity-based techniques in terms of its
      registration accuracy and is suitable for clinical procedures.

PMID- 23175166
TI  - Use of systematic surface roughing to enhance the spatial resolution of the dual
      ended readout of axially-oriented 100 mm long LYSO crystals.
AB  - In this work we explored the effects of using systematic band patterns of surface
      roughing to modulate the light transport in a dual-ended readout detector for PET
      imaging that uses 100 mm long LYSO crystals oriented in the axial direction. The
      long surfaces of 3 * 2 * 100 mm3 LYSO crystals, initially polished on all sides,
      were systematically roughed in a band pattern with 0.8 mm bands of roughed
      surface spaced at 5 mm increments over the central 8 cm of the crystal length.
      Cases of one to four surfaces of the crystal roughed with this pattern were
      explored. Two configurations of bands were examined for the opposite surfaces of
      the crystals: (i) bands created in the same axial location (coinciding bands) and
      (ii) band locations interleaved (interleaving bands). Each crystal was then
      wrapped in Teflon and read out at both ends using position sensitive
      photomultiplier tubes (PSPMTs). An electronically collimated 511 keV photon beam
      was oriented perpendicular to the long direction of the crystal and data acquired
      at discrete locations along the crystal length. The ratio of the two PMT signals
      was used to find the axial position of interaction and axial-positioning
      resolution in the light sharing direction of the dual-ended readout detector
      while their sum was used to determine the light output and energy resolution. The
      axial-positioning resolution corrected for the beam width improved from an
      average of 8.7 mm FWHM with no surface treatment to 5.9, 3.9 or 3.4 mm FWHM for
      coinciding band patterns on one, two or four surfaces, respectively. The banding
      patterns resulted in degraded energy resolution, with a decrease from 11.1% FWHM
      for the untreated crystal to 12.0%, 13.5% and 13.6% for the patterns on one, two
      and four surfaces, respectively. When the axial-positioning resolution is
      corrected for the beam width, we estimated the best resolution for the case of
      four banded surfaces to be 3.4 mm FWHM in this study. The same axial-positioning
      resolution was obtained when interleaving bands were created on only two opposite
      surfaces with a better energy resolution of 12.2%.

PMID- 23175167
TI  - Hepatitis E masquerading as drug-induced liver injury.
AB  - The patient presented below gives us the opportunity to discuss challenges in the
      diagnosis of drug-induced liver injury in an era of increasing awareness of
      hepatitis E.

PMID- 23175168
TI  - Acute care nurses' spiritual care practices.
AB  - The purpose of this study was to identify barriers in providing spiritual care to
      hospitalized patients. A convenience sample (N = 271) was recruited at an
      academic medical center in New York City for an exploratory, descriptive
      questionnaire. The Spiritual Care Practice (SCP) questionnaire assesses spiritual
      care practices and perceived barriers to spiritual care. The SCP determines the
      percentage that provides spiritual support and perceived barriers inhibiting
      spiritual care. The participation rate was 44.3% (N = 120). Most (61%) scored
      less than the ideal mean on the SCP. Although 96% (N = 114) believe addressing
      patients spiritual needs are within their role, nearly half (48%) report rarely
      participating in spiritual practices. The greatest perceived barriers were belief
      that patient's spirituality is private, insufficient time, difficulty
      distinguishing proselytizing from spiritual care, and difficulty meeting needs
      when spiritual beliefs were different from their own. Although nurses identify
      themselves as spiritual, results indicate spirituality assessments are
      inadequate. Addressing barriers will provide nurses opportunities to address
      spirituality. Education is warranted to improve nurses' awareness of the
      diversity of our society to better meet the spiritual needs of patients.
      Understanding these needs provide the nurse with opportunities to address
      spirituality and connect desires with actions to strengthen communication and the
      nurse-patient relationship.

PMID- 23175169
TI  - Postpartum weight loss: weight struggles, eating, exercise, and breast-feeding.
AB  - Twenty-four women with children 5 years old or younger were interviewed regarding
      their experiences in losing weight during the postpartum period. Phenomenological
      interviews were conducted according to Husserl's perspective. Women who
      participated in the study revealed the issues related to postpartum weight loss:
      weight struggles, exercise, breast-feeding, eating, and pregnancy contributions
      to weight gain. The overall theme that resulted from these in-depth interviews
      was that women struggle to balance their successes and setbacks in losing weight
      during the postpartum period.

PMID- 23175170
TI  - Knowing, caring, and telehealth technology: "going the distance" in nursing
      practice.
AB  - The use of technology in delivery of health care services is rapidly increasing,
      and more nurses are using telehealth to provide care by distance to persons with
      complex health challenges. The rapid uptake of telehealth modalities and dynamic
      evolution of technologies has outpaced the generation of empirical knowledge to
      support nursing practice in this emerging field, specifically in relation to how
      nurses come to know the person and engage in holistic care in a virtual
      environment. Knowing the person and nursing care have historically been
      associated with physical presence and close proximity in the nurse-client
      relationship, and the use of telehealth can limit the ways in which a nurse can
      observe the person, potentiate perceptions of distance, and lead to a
      reductionist perspective in care. The purpose of this article is to illuminate
      the dynamic and evolving nature of nursing practice in relation to the use of
      telehealth and to highlight gaps in nursing knowledge specific to knowing the
      person in a virtual environment. Such an understanding is necessary to inform
      future research and generate empirical evidence to support nurses in providing
      ethical, safe, effective, and holistic care by distance to persons through
      telehealth technology.

PMID- 23175171
TI  - Photodynamic therapy for bile duct invasion of hepatocellular carcinoma.
AB  - The prognosis of patients with obstructive jaundice caused by hepatocellular
      carcinoma (HCC) is dismal, because effective biliary drainage is difficult due to
      frequent malfunction of the drainage tube caused by hemobilia and/or tumor
      emboli. Photodynamic therapy (PDT) improves biliary patency and prolongs survival
      in hilar cholangiocarcinoma. The aim of this study was to assess the safety and
      efficacy of PDT in unresectable HCC with bile duct invasion. Between January 2009
      and September 2010, eleven patients with bile duct invasion of unresectable HCC
      were enrolled at Samsung Medical Center. PDT was performed with 180 J cm(-1)
      light activation 48 hours after administration of the photosensitizer at a dose
      of 2 mg kg(-1) body weight. Biliary drainages were performed in all patients. The
      safety and efficacy of PDT were prospectively evaluated. Eleven patients had
      successful PDT and biliary drainage. Jaundice improved in seven out of ten
      patients who had jaundice before PDT. Hemobilia, which had developed in six
      cases, was controlled by PDT. There were no complications from the
      photosensitizer. There was no 30-day mortality, and the mean survival was 140.5
      days. PDT controlled hemobilia associated with bile duct invasion of HCC and
      could be an effective treatment option in these patients.

PMID- 23175172
TI  - Differential secretome analysis of cancer-associated fibroblasts and bone marrow
      derived precursors to identify microenvironmental regulators of colon cancer
      progression.
AB  - The identification of cancer-associated fibroblast (CAF)-derived proteins that
      mediate interactions between the tumor stroma and cancer cells is a crucial step
      toward the discovery of new molecular targets for therapy or molecular signatures
      that improve tumor classification and predict clinical outcome. CAF are alpha
      smooth muscle actin positive, representing a myofibroblast phenotype that may
      differentiate from multiple precursor cells, including bone marrow-derived
      mesenchymal stem cells (MSC). Transforming growth factor-beta1 (TGF-beta1) is a
      crucial inducer of alpha-smooth muscle actin positive CAFs. In this study, we
      aimed to identify CAF-derived regulators of colon cancer progression by
      performing a high-throughput differential secretome profiling between CAF
      compared to noncancer-activated bone marrow-derived MSC. In addition, we explored
      the effect of TGF-beta1 on the secretion of proteins by bone marrow-derived MSC
      in comparison with the protein secretion profile of CAF. TGF-beta1 induced de
      novo secretion of 84 proteins in MSC, of which 16 proteins, including stromal
      derived factor-1alpha and Rantes, were also present in CAF secretome.
      Immunohistochemistry further validated the expression of selected candidates such
      as tenascin C, fibronectin ED-A domain and stromal-derived factor-1 in clinical
      colon cancer specimens. In conclusion, this differential secretome approach
      enabled us to identify a series of candidate biomarkers for colon cancer that are
      associated with a CAF-specific phenotype.

PMID- 23175173
TI  - Distinct expression of C4.4A in colorectal cancer detected by different
      antibodies.
AB  - The metastasis-associated gene C4.4A encodes a glycolipid-anchored membrane
      protein expressed in several human malignancies. The present study aimed to
      perform a detailed assessment of C4.4A expression in colorectal cancer tissues,
      in terms of intra-cellular localization, intra-tumoral location and difference in
      molecular weight. To advance this goal, we developed three new antibodies against
      the C4.4A protein (two polyclonal Abs: C4.4A-119 and C4.4A-277 and one monoclonal
      Ab: C4.4A GPI-M) to use in addition to the two previously produced polyclonal Abs
      (C4.4A-81, C4.4A GPI-P). Antibody specificities were confirmed by absorption
      tests. Western blot analysis and immunohistochemistry showed that the C4.4A-119
      and C4.4-277 Abs detected 70-kDa C4.4A, mainly in the cytoplasm, irrespective of
      intra-tumoral location. The C4.4A GPI-P and C4.4A GPI-M Abs reacted with the
      membranous ~40-kDa C4.4A, exclusively at the tumor invasive front, and each
      detected an identical tumor cell population. The tested antibodies showed varied
      C4.4A detection rates in 33 CRC tissues. The C4.4A-277 Ab yielded the highest
      positive rate in 29 of 33 CRC tissues (87.9%), while the C4.4A GPI-P and C4.4A
      GPI-M Abs each only showed 33.3% positivity. The present findings suggest that
      the GPI anchor signaling sequence may be essential for detecting membranous C4.4A
      at the invasive front of CRC tissues.

PMID- 23175174
TI  - Augmentation of ADAMTS9 gene expression by IL-1beta is reversed by NFkappaB and
      MAPK inhibitors, but not PI3 kinase inhibitors.
AB  - The pathways involved in the regulation of a disintegrin and metalloproteinase
      with thrombospondin motifs 9 (ADAMTS9) expression have not yet been elucidated.
      Therefore, the aim of this study was to investigate the involvement of nuclear
      factor-kappaB (NF-kappaB), mitogen activated protein kinases (MAPK) and
      Phosphatidylinositol 3-kinase (PI3 kinase) in ADAMTS9 gene regulation, with
      special focus on the involvement of NF-kappaB in IL-1beta-induced ADAMTS9
      expression. The OUMS-27 chondrosarcoma cells were exposed to IL-1beta. They were
      pretreated with 20 MUM PD98059 (specific inhibitor of p44/42 kinase), 10 MUM
      SB203580 (specific inhibitor of p38 kinase), 20 MUM SB600125 (MAPK inhibitor),
      and 1 MUM Wortmannin and 10 MUM LY294002 (specific inhibitors of PI3 kinase) for
      30 min and subsequently incubated with IL-1beta. For the effects of NF-kappaB and
      IkappaB inhibitors, cells were pretreated with curcumin or BAY117085 for 30 min
      and subsequently incubated with IL-1beta. BAY117085 and different concentrations
      of curcumin were applied to the cells just after the first experiment to
      determine their concentration effect on ADAMTS9 gene expression. After total RNA
      was extracted, they were reversely transcribed with random primers and then real
      time polymerase chain reaction (PCR) was performed on cDNA samples. There was a
      significant difference between control and stimulated cells in terms of
      ADAMTS9/beta-actin ratio. Wortmannin and LY294002 did not have any repressive
      effect on the OUMS-27 whereas SB203580 and SP600125 were found to decrease the
      expression of ADAMTS9 gene. BAY 117085 and curcumin, which are two NF-kappaB
      inhibitors, led to a decrease in the ratio of ADAMTS9/beta-actin. As a
      conclusion, the pathways MAPK and NF-kappaB were thought to be responsible
      pathways for the induction of ADAMTS9 gene.

PMID- 23175175
TI  - Induction of differentiation-specific miRNAs in TPA-induced myeloid leukemia
      cells through MEK/ERK activation.
AB  - Cellular microRNAs (miRNAs) are pivotal regulators involved in various biological
      processes through the post-transcriptional regulation of gene expression.
      Signaling pathways are extensively activated during 12-O-Tetradecanoylphorbol-13
      acetate (TPA)-induced differentiation of human leukemia cells, but the modulation
      of miRNA expression and processing in this context has yet to be fully explored.
      In this study, we comprehensively analyzed 10 miRNAs that are consistently
      upregulated during TPA-induced differentiation of various leukemia cell lines by
      employing microarray technology. The upregulation of these miRNAs was further
      verified by quantitative RT-PCR, and, markedly, a subset of the miRNAs was found
      to be induced via the MEK/ERK signaling pathway using TPA and specific
      pharmacological inhibitors. Moreover, immunoblotting and quantitative RT-PCR
      analysis demonstrated that the expression levels of key miRNA processing
      machineries (i.e., Drosha, Dicer, Ago1 and Ago2) were not induced in this
      context, but the transcription of the miRNA products was triggered by MEK/ERK
      activation. Therefore, we identified the unique miRNAs that respond to TPA
      treatment in leukemia cells and demonstrated the essential role of the MEK/ERK
      signaling pathway in the induction of these miRNA transcripts.

PMID- 23175176
TI  - Variation in PAH-related DNA adduct levels among non-smokers: the role of
      multiple genetic polymorphisms and nucleotide excision repair phenotype.
AB  - Polycyclic aromatic hydrocarbons (PAHs) likely play a role in many cancers even
      in never-smokers. We tried to find a model to explain the relationship between
      variation in PAH-related DNA adduct levels among people with similar exposures,
      multiple genetic polymorphisms in genes related to metabolic and repair pathways,
      and nucleotide excision repair (NER) capacity. In 111 randomly selected female
      never-smokers from the Golestan Cohort Study in Iran, we evaluated 21 SNPs in 14
      genes related to xenobiotic metabolism and 12 SNPs in eight DNA repair genes. NER
      capacity was evaluated by a modified comet assay, and aromatic DNA adduct levels
      were measured in blood by32P-postlabeling. Multivariable regression models were
      compared by Akaike's information criterion (AIC). Aromatic DNA adduct levels
      ranged between 1.7 and 18.6 per 10(8) nucleotides (mean: 5.8 +/- 3.1). DNA adduct
      level was significantly lower in homozygotes for NAT2 slow alleles and ERCC5 non
      risk-allele genotype, and was higher in the MPO homozygote risk-allele genotype.
      The sum of risk alleles in these genes significantly correlated with the log
      adduct level (r = 0.4, p < 0.001). Compared with the environmental model, adding
      Phase I SNPs and NER capacity provided the best fit, and could explain 17% more
      of the variation in adduct levels. NER capacity was affected by polymorphisms in
      the MTHFR and ERCC1 genes. Female non-smokers in this population had PAH-related
      DNA adduct levels three to four times higher than smokers and occupationally
      exposed groups in previous studies, with large inter-individual variation which
      could best be explained by a combination of Phase I genes and NER capacity.

PMID- 23175177
TI  - Role of block copolymer-micelle nanocomposites in dye-bovine serum albumin
      binding: a combined experimental and molecular docking study.
AB  - The role of a nanocomposite (NC), composed of intercalation of the diblock
      copolymer polyethylene-b-polyethylene glycol (PE-b-PEG) with the anionic
      surfactant sodium dodecyl sulphate (SDS), on the binding characteristics of
      bovine serum albumin (BSA) with a dye (1,8-naphthalimide, NAPMD) compared to the
      interaction between the same players in aqueous solution has been examined
      comprehensively in this paper. Static quenching due to complex formation in both
      NC medium and in buffer solution has been inferred on the basis of considerable
      changes in the absorption spectra of BSA on addition of NAPMD, of which the
      interaction is found to be stronger in NC medium. Temperature dependent
      fluorescence data also confirm an effective static quenching and stronger binding
      of NAPMD with BSA in NC medium. Peptide chain unfolding and denaturing of BSA in
      NC medium have been confirmed from steady state and time-resolved emission and
      circular dichroism data. This exposes both the tyrosine and tryptophan moieties
      as a unique case. Increased energy transfer between NAPMD and the tryptophan
      residue in the unfolded form of BSA helps in the appearance of tyrosine
      fluorescence in NC medium by quenching the tryptophan band. Ionization of the
      hydroxyl group in the aromatic ring of the tyrosine residue by the PEG group
      present in the NC medium produces a downshift of the tyrosine fluorescence band.
      The use of site selective markers confirms that NAPMD is near tryptophan in
      Sudlow's site I in NC medium and in buffer solution it is away from tryptophan in
      Sudlow's site II. The theoretical docking studies also vindicate the results of
      binding of NAPMD with BSA in site I or site II in NC and buffer media, as
      observed from different emission experiments including the site selective markers
      study.

PMID- 23175178
TI  - Acute changes in postural control after soccer heading.
AB  - This study intended to determine if an acute bout of soccer heading alters
      postural control and pronounced self-reported symptoms of cerebral concussion.
      Collegiate soccer players were randomly assigned to one of 2 groups. Each
      participant completed a baseline postural control assessment prior to heading.
      Participants either simulated (control group; CG) or performed (experimental
      group; EG) 10 headers at 11.2 m/s in 10 min. The postural assessment was repeated
      post heading at hrs 1, 24, and 48. The postural control parameter assessed was
      the root mean square (RMS) of the center of mass (COM). COM RMS were calculated
      for the anterior-posterior (AP) and medial-lateral (ML) time series. Compared to
      the CG, for the AP and ML time series COM RMS values were significantly higher in
      the EG at hr 24 (p <0.05). An acute bout of heading results in quantifiable
      alterations in postural control that are detectable 24 h post heading and
      dissipate within an additional 24 h. The significant findings may be due to the
      dynamic postural control assessment that incorporated robust discordant
      environmental conditions.

PMID- 23175179
TI  - Cardiac work remains high after strength exercise in elderly.
AB  - Moderate- to high-intensity strength training is recommended for healthy adults.
      In young subjects, a single session of strength training decreases blood
      pressure, while heart rate and cardiac work remain elevated afterwards. However,
      these effects have not been clearly demonstrated in elderly subjects. To
      investigate this issue, 16 elderly subjects each underwent a Control and an
      Exercise (3 sets, 8 RM, 9 exercises) session conducted in random order.
      Haemodynamic variables and heart rate variability were measured before and after
      the interventions. Systolic blood pressure did not change after the exercise
      session but did increase after the control session (+8.1+/-1.6 mm Hg, P<=0.05).
      Diastolic blood pressure, as well as systemic vascular resistance increased
      similarly after both sessions. Cardiac output and stroke volume decreased, while
      heart rate, rate-pressure product and the low- to high-frequency ratio of heart
      rate variability increased only after the exercise session ( - 0.5+/-0.1 L/min, -
      9.3+/-2.0 ml,+3.8+/-1.6 bpm, +579.3+/-164.1 mmHg.bpm and +0.71+/-0.34, P<=0.05).
      Ambulatory blood pressure was similar after both sessions, while heart rate and
      rate pressure product remained higher after the exercise session for up to 4.5 h.
      After a single session of strength training, cardiac sympathetic modulation and
      heart rate remain elevated in elderly subjects, keeping cardiac work elevated for
      a long period of time.

PMID- 23175180
TI  - Cardiac vagal index does not explain age-independent maximal heart rate.
AB  - Cardiac vagal tone (CVT), a key determinant of resting heart rate (HR), is
      progressively withdrawn with incremental exercise and nearly abolished at maximal
      effort. While maximal HR decreases with age, there remains a large
      interindividual variability of results for any given age. In the present study,
      we hypothesized that CVT does not contribute to age-independent maximal HR. Data
      were obtained from 1 000 (39+/-14 years old) healthy subjects (719 men) who were
      not taking medications affecting CVT or maximal HR performed a clinically normal
      and truly maximal cardiopulmonary exercise testing. CVT was estimated using the
      cardiac vagal index (CVI), a dimensionless ratio obtained by dividing 2 cardiac
      cycle durations--end of exercise and pre-exercise--, reflecting HR increases
      during a 4-s unloaded cycling test (a vagally-mediated response). Maximal HR was
      expressed as % of that predicted by age (208-0.7 * age (years)). Linear
      regression analyses identified that CVI can explain only 1% of the % age
      predicted maximal HR variability with a high standard error of estimate (~6.3%),
      indicating the absence of a true physiological cause-effect relationship. In
      conclusion, the influence of CVI on % of age-predicted maximal HR is null in
      healthy subjects, suggesting distinct physiological mechanisms and potential
      clinical complementary role for these exercise-related variables.

PMID- 23175181
TI  - Measurement accuracy of heart rate and respiratory rate during graded exercise
      and sustained exercise in the heat using the Zephyr BioHarness.
AB  - The Zephyr BioHarness was tested to determine the accuracy of heart rate (HR) and
      respiratory rate (RR) measurements during 2 exercise protocols in conjunction
      with either a laboratory metabolic cart (Vmax) or a previously validated portable
      metabolic system (K4b2). In one protocol, HR and RR were measured using the
      BioHarness and Vmax during a graded exercise up to VO2max (n=12). In another
      protocol, HR and RR were measured using the BH and K4b2 during sustained exercise
      (30% and 50% VO2max for 20 min each) in a hot environment (30  degrees C, 50%
      relative humidity) (n=6). During the graded exercise, HR but not RR, obtained
      from the BioHarness was higher compared to the Vmax at baseline and 30% VO2max
      (p<0.05), but showed no significant difference at other stages with high
      correlation coefficients for both HR (r=0.87-0.96) and RR (r=0.90-0.99 above 30%
      VO2max). During the exercise in the heat, there were no significant differences
      between the BioHarness and K4b2 system. Correlation coefficients between the
      methods were low for HR but moderately to highly correlated (0.49-0.99) for RR.
      In conclusion, the BioHarness is comparable to Vmax and K4b2 over a wide range of
      VO2 during graded exercise and sustained exercise in the heat.

PMID- 23175182
TI  - Type-3 metabotropic glutamate receptors regulate chemoresistance in glioma stem
      cells, and their levels are inversely related to survival in patients with
      malignant gliomas.
AB  - Drug treatment of malignant gliomas is limited by the intrinsic resistance of
      glioma stem cells (GSCs) to chemotherapy. GSCs isolated from human glioblastoma
      multiforme (GBM) expressed metabotropic glutamate receptors (mGlu3 receptors).
      The DNA-alkylating agent, temozolomide, killed GSCs only if mGlu3 receptors were
      knocked down or pharmacologically inhibited. In contrast, mGlu3 receptor blockade
      did not affect the action of paclitaxel, etoposide, cis-platinum, and irinotecan.
      mGlu3 receptor blockade enabled temozolomide toxicity by inhibiting a
      phosphatidylinositol-3-kinase/nuclear factor-kappaB pathway that supports the
      expression of O(6)-methylguanine-DNA methyltransferase (MGMT), an enzyme that
      confers resistance against DNA-alkylating agents. In mice implanted with GSCs
      into the brain, temozolomide combined with mGlu3 receptor blockade substantially
      reduced tumor growth. Finally, 87 patients with GBM undergoing surgery followed
      by adjuvant chemotherapy with temozolomide survived for longer time if tumor
      cells expressed low levels of mGlu3 receptors. In addition, the methylation state
      of the MGMT gene promoter in tumor extracts influenced survival only in those
      patients with low expression of mGlu3 receptors in the tumor. These data
      encourage the use of mGlu3 receptor antagonists as add-on drugs in the treatment
      of GBM, and suggest that the transcript of mGlu3 receptors should be measured in
      tumor specimens for a correct prediction of patients' survival in response to
      temozolomide treatment.

PMID- 23175183
TI  - A role for c-FLIP(L) in the regulation of apoptosis, autophagy, and necroptosis
      in T lymphocytes.
AB  - Caspase 8 plays a dual role in the survival of T lymphocytes. Although active
      caspase 8 mediates apoptosis upon death receptor signaling, the loss of caspase 8
      activity leads to receptor-interacting protein (RIP)-1/RIP-3-dependent necrotic
      cell death (necroptosis) upon TCR activation. The anti-apoptotic protein c-FLIP
      (cellular caspase 8 (FLICE)-like inhibitory protein) suppresses death receptor
      induced caspase 8 activation. Moreover, recent findings suggest that c-FLIP is
      also involved in inhibiting necroptosis and autophagy. It remains unclear whether
      c-FLIP protects primary T lymphocytes from necroptosis or regulates the threshold
      at which autophagy occurs. Here, we used a c-FLIP isoform-specific conditional
      deletion model to show that c-FLIP(L)-deficient T cells underwent RIP-1-dependent
      necroptosis upon TCR stimulation. Interestingly, although previous studies have
      only described necroptosis in the absence of caspase 8 activity, we found that
      pro-apoptotic caspase 8 activity and apoptosis were also enhanced in c-FLIP(L)
      deficient T lymphocytes. Furthermore, c-FLIP(L)-deficient T cells exhibited
      enhanced autophagy, which served a cytoprotective function. Together, these
      findings indicate that c-FLIP(L) plays an important antinecroptotic role and is a
      key regulator of apoptosis, autophagy, and necroptosis in T lymphocytes.

PMID- 23175184
TI  - Blebbishields, the emergency program for cancer stem cells: sphere formation and
      tumorigenesis after apoptosis.
AB  - Caspases mediate apoptosis and have also been implicated in stem-cell biology.
      How caspases are linked to stem-cell biology is not known. Here, we show that the
      apoptotic blebs of cancer cells fuse together to form novel structures called
      'blebbishields'. Blebbishields form spheres by fusion. Both blebbishield
      formation and sphere formation involve active caspases and N-linked
      glycosylation. Sphere formation is enhanced by acidic pH and is counteracted by
      inhibitors of proton pump, caspases, and cholesterol. The blebbishields from
      VEGFR2(High) cells are capable of enhanced sphere formation. Blebbishields
      express transiently downregulated stem-cell markers and the sphere-forming
      blebbishield-derived cells are tumorigenic. Our study demonstrates that the
      cancer stem cells can survive after apoptosis by blebbishield formation and
      subsequent sphere formation.

PMID- 23175185
TI  - CCN2 inhibits lung cancer metastasis through promoting DAPK-dependent anoikis and
      inducing EGFR degradation.
AB  - CCN family protein 2 (CCN2), also known as connective tissue growth factor, is a
      secreting protein that modulates multiple cellular events. We previously
      demonstrated the metastasis-suppressive effect of CCN2 in lung cancer cells. In
      this study, we investigate the role of CCN2 in anoikis, a form of programmed cell
      death that is critical in suppressing cancer metastasis. CCN2 binds to the
      epidermal growth factor receptor (EGFR) and triggers ubiquitination by inhibiting
      the formation of the beta-pix/Cbl complex, resulting in the degradation of EGFR.
      Binding of CCN2 to EGFR suppresses the phosphorylation of c-Src and extracellular
      signal-regulated kinase but increases the expression of death-associated protein
      kinase, which leads to anoikis. Overall, our findings provide evidence validating
      the use of CCN2 as an anti-metastatic therapy in lung cancer patients, and
      prospect a potential therapeutic synergy between CCN2 and the anti-EGFR antibody
      for the treatment of lung cancer.

PMID- 23175186
TI  - T-cell death following immune activation is mediated by mitochondria-localized
      SARM.
AB  - Following acute-phase infection, activated T cells are terminated to achieve
      immune homeostasis, failure of which results in lymphoproliferative and
      autoimmune diseases. We report that sterile alpha- and heat armadillo-motif
      containing protein (SARM), the most conserved Toll-like receptors adaptor, is
      proapoptotic during T-cell immune response. SARM expression is significantly
      reduced in natural killer (NK)/T lymphoma patients compared with healthy
      individuals, suggesting that decreased SARM supports NK/T-cell proliferation. T
      cells knocked down of SARM survived and proliferated more significantly compared
      with wild-type T cells following influenza infection in vivo. During activation
      of cytotoxic T cells, the SARM level fell before rising, correlating inversely
      with cell proliferation and subsequent T-cell clearance. SARM knockdown rescued T
      cells from both activation- and neglect-induced cell deaths. The mitochondria
      localized SARM triggers intrinsic apoptosis by generating reactive oxygen species
      and depolarizing the mitochondrial potential. The proapoptotic function is
      attributable to the C-terminal sterile alpha motif and Toll/interleukin-1
      receptor domains. Mechanistically, SARM mediates intrinsic apoptosis via B cell
      lymphoma-2 (Bcl-2) family members. SARM suppresses B cell lymphoma-extra large
      (Bcl-xL) and downregulates extracellular signal-regulated kinase phosphorylation,
      which are cell survival effectors. Overexpression of Bcl-xL and double knockout
      of Bcl-2 associated X protein and Bcl-2 homologous antagonist killer
      substantially reduced SARM-induced apoptosis. Collectively, we have shown how T
      cell death following infection is mediated by SARM-induced intrinsic apoptosis,
      which is crucial for T-cell homeostasis.

PMID- 23175187
TI  - TLR2-dependent selective autophagy regulates NF-kappaB lysosomal degradation in
      hepatoma-derived M2 macrophage differentiation.
AB  - Autophagy is a lysosomal pathway for cellular homeostasis control. Both non
      selective bulk autophagy and selective autophagy of specific proteins or
      organelles have been found. Selective autophagy prevents cells from pathogen
      invasion and stress damage, but its role in regulating transcriptional factors is
      not clear. Using a macrophage cell differentiation model, the role of autophagy
      in nuclear factor-kappaB (NF-kappaB) regulation is investigated. The bone marrow
      derived macrophages (BMDMs) will differentiate into a M2-like phenotype in the
      presence of hepatoma tumor cell condition medium (CM). The TLR2 signaling drives
      this M2 polarization and causes NF-kappaB p65 degradation via lysosome-dependent
      pathway. The CM-induced ubiquitinated- NF-kappaB p65 forms aggresome-like
      structures (ALS) in the cytoplasm of cultured and hepatoma-associated M2
      macrophages. This NF-kappaB p65-contained ALS is recognized by p62/SQSTM1 and
      degraded by selective autophagy. Treatment with the lysosomal inhibitor
      bafilomycin A1 or the knockdown of Atg5 can prevent CM-induced NK-kappaB p65
      degradation and induce M2 macrophages to produce a high level of pro-inflammatory
      cytokines. Furthermore, TLR2 signal induces sustained phosphorylation of
      extracellular signal-regulated kinase 1/2 to facilitate this autophagy-dependent
      NF-kappaB regulation. Our finding provides a novel pathway of NF-kappaB
      regulation by p62/SQSTM1-mediated selective autophagy.

PMID- 23175189
TI  - MIRUMIR: an online tool to test microRNAs as biomarkers to predict survival in
      cancer using multiple clinical data sets.

PMID- 23175190
TI  - Redox active aluminium(III) complexes convert CO2 into MgCO3 or CaCO3 in a
      synthetic cycle using Mg or Ca metal.
AB  - Redox-active Group 13 molecules possess the unusual combination of concomitant
      redox and acid-base reactivity. These combined properties enable regeneration of
      a metal hydroxide complex in a cycle for conversion of CO2 into carbonate salts.
      Reaction of (IP(-))2Al(OH) (M = Al, Ga) with 1 atm of CO2 affords [(IP(
      ))2Al]2(MU(2)kappa(1):kappa(2)-OCO2). Subsequent reduction affords MgCO3 or CaCO3
      and two equivalents of [(IP(2-))2Al](-), which can be reoxidized to (IP(
      ))2Al(OH) to close a cycle.

PMID- 23175191
TI  - The metabolic deterioration that antedates diabetes: personal trajectories of
      HbA(1c)  and fasting glucose as early indicators and possible triggers for
      intervention.
AB  - HbA(1c) testing has become an accepted means of diagnosing diabetes as an
      alternative to blood glucose levels. However, population-based norms of glucose
      and of HbA(1c) levels do not enable the detection of diabetes at an early enough
      stage to thwart complications. Personal trajectories of glucose levels show steep
      increases a number of years prior to diabetes diagnosis. Here, we hypothesize
      that a comparable time-dependent deviation in an individual's HbA(1c) level may
      be an early manifestation of disease that should prompt lifestyle modifications.
      We predict that analysis of personal trajectories of glucose and of HbA(1c) will
      promote earlier intervention and a greater reduction in disease complications
      than current standards, which are based on population-based norms.

PMID- 23175188
TI  - The histone deacetylase SIRT2 stabilizes Myc oncoproteins.
AB  - Myc oncoproteins are commonly upregulated in human cancers of different organ
      origins, stabilized by Aurora A, degraded through ubiquitin-proteasome pathway
      mediated proteolysis, and exert oncogenic effects by modulating gene and protein
      expression. Histone deacetylases are emerging as targets for cancer therapy. Here
      we demonstrated that the class III histone deacetylase SIRT2 was upregulated by N
      Myc in neuroblastoma cells and by c-Myc in pancreatic cancer cells, and that
      SIRT2 enhanced N-Myc and c-Myc protein stability and promoted cancer cell
      proliferation. Affymetrix gene array studies revealed that the gene most
      significantly repressed by SIRT2 was the ubiquitin-protein ligase NEDD4.
      Consistent with this finding, SIRT2 repressed NEDD4 gene expression by directly
      binding to the NEDD4 gene core promoter and deacetylating histone H4 lysine 16.
      Importantly, NEDD4 directly bound to Myc oncoproteins and targeted Myc
      oncoproteins for ubiquitination and degradation, and small-molecule SIRT2
      inhibitors reactivated NEDD4 gene expression, reduced N-Myc and c-Myc protein
      expression, and suppressed neuroblastoma and pancreatic cancer cell
      proliferation. Additionally, SIRT2 upregulated and small-molecule SIRT2
      inhibitors decreased Aurora A expression. Our data reveal a novel pathway
      critical for Myc oncoprotein stability, and provide important evidences for
      potential application of SIRT2 inhibitors for the prevention and therapy of Myc
      induced malignancies.

PMID- 23175192
TI  - Predicting dementia or diagnosing early stages of Alzheimer's disease? How the
      hippocampal volume and the Clinical Dementia Rating-SB can help early diagnosis.

PMID- 23175193
TI  - Parkinson's disease and body mass index: too much or too little?

PMID- 23175194
TI  - Hippocampal volume and CDR-SB can predict conversion to dementia in MCI patients.
AB  - OBJECTIVE: To evaluate the combination of two factors: clinical dementia rating
      sum of boxes scores (CDR-SB) and hippocampal volume (HV) as predictors of
      conversion from mild cognitive impairment (MCI) to dementia. METHODS: Twenty
      eight individuals (9 normal and 19 with MCI) were classified according to their
      CDR sum of boxes scores into 3 groups. RESULTS: The hippocampal volume was
      significantly lower in the high-risk group and in those who developed dementia
      after two years. The rate of conversion was crescent among the three groups.
      CONCLUSION: We were proposed an additional measurement of the hippocampal volume
      which may be helpful in the prognosis. However, we noted that the CDR-SB is a
      method as efficient as neuroimaging to predict dementia with the advantage of
      being a procedure for low cost and easy implementation, more consistent with
      public policy.

PMID- 23175195
TI  - Overweight is more prevalent in patients with Parkinson's disease.
AB  - Underweight and malnutrition are well documented in Parkinson's disease (PD),
      while overweight has been less reported. We carried out a cross-sectional study
      including 177 healthy controls and 177 PD patients attending a tertiary care
      center. We recorded weight and height for all participants. A statistically
      significant difference was found in body mass index (BMI) between controls and PD
      patients (29.1+/-5.4 versus 27.2+/-4.7, p<0.001). In the PD Group, two patients
      were underweight, 32.7% were within normal range, 46.9% had overweight, and 19.2%
      were obese. Overweight and normal weight were more prevalent in the PD Group
      (p=<0.01 and <0.001, respectively) when compared to controls. In conclusion,
      overweight/obesity are common among patients with PD, while underweight is almost
      negligible.

PMID- 23175196
TI  - Respiratory changes in Parkinson's disease may be unrelated to dopaminergic
      dysfunction.
AB  - OBJECTIVE: To investigate the maximal inspiratory pressure (MIP) and maximal
      expiratory pressure (MEP) in patients with Parkinson's disease (PD) during the on
      and off periods of levodopa and to compare with healthy controls. METHODS: Twenty
      six patients were analyzed with Hoehn and Yahr scores (2-3) and 26 age and gender
      matched-controls. Statistical analysis was performed with Student's t-test for
      paired and independent samples. RESULTS: MIP and MEP values in patients were
      significantly lower than the values obtained in controls both for off and on
      stages -excepted for MIP in women (p=0.28). For patients with PD, the studied
      parameters did not differ between stages on and off, with the exception of MEP in
      women (p=0.00). CONCLUSIONS: Patients with PD have respiratory pressure lower
      than controls, even in early stages of the disease, and dopamine replacement has
      little impact over these respiratory pressures. These findings suggest that
      respiratory changes in PD may be unrelated to dopaminergic dysfunction.

PMID- 23175197
TI  - 12 item allodynia symptom checklist/Brasil: cross-cultural adaptation, internal
      consistency and reproducibility.
AB  - Since there was no Portuguese questionnaire to evaluate cutaneous allodynia,
      which has been pointed out as a risk factor of migraine, we aimed to perform the
      cross-cultural adaptation of the 12 item Allodynia Symptom Checklist for the
      Brazilian population and to test its measurement properties. It consisted in six
      stages: translation, synthesis, back translation, revision by a specialist
      committee, pretest and submission the documents to the committee. In the pretest
      stage, the questionnaire was applied to 30 migraineurs of both sexes, who had
      some difficulty in understanding it. Thus, a second version was applied to 30
      additional subjects, with no difficulties being reported. The mean filling out
      time was 3'36", and the internal consistency was 0.76. To test reproducibility,
      15 other subjects filled out the questionnaire at two different times, it was
      classified as moderate (weighted kappa=0.58). We made available to Brazilian
      population an easy, quick and reliable questionnaire.

PMID- 23175198
TI  - Axis instrumentation: surgical results.
AB  - OBJECTIVE: Evaluate the surgical results of axis screw instrumentation. METHODS:
      Retrospective evaluation of the clinical and radiological data of patients
      submitted to axis fixation using screws. RESULTS: Seventeen patients were
      surgically treated. The mean age was 41.8 years (range: 12-73). Spinal cord
      trauma was the most common cause of instability (8 patients - 47%). Bilateral
      axis fixation was performed in all cases, except one, with laminar screw (total
      of 33 axis screws). Seven patients (41.1%) underwent bilateral pars screws;
      laminar screws were used in six cases and pedicular screws were used in two. In
      two cases, we performed a hybrid construction (laminar + pars and pedicle +
      pars). There was no neurological worsening or death, nor complications directly
      related to use axis screws. CONCLUSION: Axis instrumentation was effective and
      safe, regardless of the technique used for stabilization. Based on our learnt
      experience, we proposed an algorithm to choose the best technique for axis screw
      fixation.

PMID- 23175199
TI  - The cognitive behavioral therapy causes an improvement in quality of life in
      patients with chronic musculoskeletal pain.
AB  - Chronic pain causes functional incapacity and compromises an individual's
      affective, social, and economic life. OBJECTIVE: To study the cognitive
      behavioral therapy (CBT) effectiveness in a group of patients with chronic pain.
      METHODS: A randomized clinical trial with two parallel groups comprising 93
      patients with chronic pain was carried out. Forty-eight patients were submitted
      to CBT and 45 continued the standard treatment. The visual analogue, hospital
      anxiety and depression, and quality of life SF-36 scales were applied. Patients
      were evaluated before and after ten weeks of treatment. RESULTS: When the Control
      Group and CBT were compared, the latter presented reduction of depressive
      symptoms (p=0.031) and improvement in the domains 'physical limitations'
      (p=0.012), 'general state of health' (p=0.045), and 'limitations by emotional
      aspects' (p=0.025). CONCLUSIONS: The CBT was effective and it has caused an
      improvement in more domains of quality of life when compared to the Control
      Group, after ten weeks of treatment.

PMID- 23175200
TI  - Early stroke case-fatality rates in three hospital registries in the Northeast
      and Southeast of Brazil.
AB  - Few studies have addressed early cerebrovascular lethality in Brazil. OBJECTIVE:
      To evaluate 10 and 28-day stroke case-fatality rates in three hospitals in three
      Brazilian cities. METHODS: We described the stroke registries in Sao Paulo, Joao
      Pessoa, and Natal. RESULTS: Out of a total of 962 first-ever events (mean age,
      68.1 years-old; 53% men), 83.6% (804 cases) were classified as ischemic and 16.4%
      (158) as hemorrhagic stroke. Overall, the case-fatality rates and 95% confidence
      intervals (95%CI) for hemorrhagic stroke events were higher than for ischemic
      events, both at 10 (12.3%; 95%CI 7.2-17.4 versus 7.0%; 95%CI 5.3-8.8) and at 28
      days (19.8%; 95%CI 13.6-26.0 versus 11.1%; 95%CI 8.9-13.3). CONCLUSIONS: We did
      not find any substantial differences in early case-fatality rates according to
      stroke subtypes, when comparing the three centers.

PMID- 23175201
TI  - Decreased nitric oxide levels in the hippocampus may play a role in learning and
      memory deficits in ovariectomized rats treated by a high dose of estradiol.
AB  - The effects of a high estradiol dose on memory and on nitric oxide metabolites in
      hippocampal tissues were investigated. Sham-Est and OVX-Est Groups were treated
      with 4 mg/kg of estradiol valerate for 12 weeks. Time latency and path length
      were significantly higher in the Sham-Est and OVX-Est Groups than in the Sham and
      OVX Groups, respectively (p<0.001). The animals in the Sham-Est and OVX-Est
      Groups spent lower time in the target quadrant (Q1) than those of the Sham and
      OVX Groups during the probe trial test (p<0.05 and <0.001, respectively).
      Significantly lower nitric oxide metabolite levels in the hippocampi of the Sham
      Est and OVX-Est Groups were observed than in the Sham and OVX ones (p<0.001).
      These results suggest that decreased nitric oxide levels in the hippocampus may
      play a role in the learning and memory deficits observed after treatment with a
      high dose of estradiol, although the precise underlying mechanisms remain to be
      elucidated.

PMID- 23175202
TI  - Spinal cord injury as a trigger to develop periodic leg movements during sleep:
      an evolutionary perspective.
AB  - The primary trigger to periodic limb movement (PLM) during sleep is still
      unknown. Its association with the restless legs syndrome (RLS) is established in
      humans and was reported in spinal cord injury (SCI) patients classified by the
      American Spinal Injury Association (ASIA) as A. Its pathogenesis has not been
      completely unraveled, though recent advances might enhance our knowledge about
      those malfunctions. PLM association with central pattern generator (CPG) is one
      of the possible pathologic mechanisms involved. This article reviewed the
      advances in PLM and RLS genetics, the evolution of CPG functioning, and the
      neurotransmitters involved in CPG, PLM and RLS. We have proposed that SCI might
      be a trigger to develop PLM.

PMID- 23175204
TI  - Meynert and the biological German psychiatry.
AB  - Theodor Hermann Meynert (1833-1892), a German-Austrian neuropathologist and
      anatomist, is known as one of the founders of the Brain Psychiatry. He was the
      most arduous defender of the bridge between psychological and neurophysiological
      events, both dependent on specific neuroanatomical structures. Juliano Moreira
      (1873-1933), the founder of the Brazilian scientific psychiatry, is also
      mentioned, as well as the influence he received from the German psychiatry,
      mainly Emil Kraepelin's (1856-1926). Finally, the rapprochement of Psychiatry and
      Neurology is considered mostly in common areas as Neuropsychiatry.

PMID- 23175203
TI  - Guidelines for acute ischemic stroke treatment: part II: stroke treatment.
AB  - The second part of these Guidelines covers the topics of antiplatelet,
      anticoagulant, and statin therapy in acute ischemic stroke, reperfusion therapy,
      and classification of Stroke Centers. Information on the classes and levels of
      evidence used in this guideline is provided in Part I. A translated version of
      the Guidelines is available from the Brazilian Stroke Society website
      (www.sbdcv.com.br).

PMID- 23175205
TI  - Charcot's skepticism.
AB  - This paper brings a short review about a peculiar characteristic of Professor
      Charcot, the father of neurology: the skepticism, emphasizing his personal view
      regarding the prognosis of several neurological conditions.

PMID- 23175206
TI  - Hereditary sensory and autonomic neuropathy type 3 in non-Jewish child.

PMID- 23175207
TI  - Subcostal schwannoma in pregnancy.

PMID- 23175208
TI  - Intracerebral microbleeds in sepsis: susceptibility-weighted MR imaging findings.

PMID- 23175209
TI  - Critical basilar expansion of the sphenoidal sinus associated with a spontaneous
      cerebrospinal fluid fistula: the relevance of multidetector computed tomographic
      cisternography.

PMID- 23175210
TI  - Cervical gunshot wound: bullet trajectory on three-dimensional computed
      tomography scan.

PMID- 23175211
TI  - Bath-related headache induced by varenicline.

PMID- 23175213
TI  - Gambogic acid inhibits invasion of osteosarcoma via upregulation of TIMP-1.
AB  - Gambogic acid (GA), the natural product, has been demonstrated to be a promising
      chemotherapeutic drug for osteosarcoma (OS) due to its ability to induce
      apoptosis and cell cycle arrest. To date, no studies have examined the role of GA
      in metastatic bone disease. Matrix metalloproteinases (MMPs) play critical roles
      in invasion and metastasis, and the tissue inhibitors of metalloproteinase (TIMP)
      family regulates the activity of multifunctional metalloproteinases. In this
      study, we investigated the gene expression of matrix metalloproteinase-9 (MMP-9)
      and tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) in OS cell lines
      treated by the GA. The expression of MMP-9 and TIMP-1 were studied by reverse
      transcription-polymerase chain reaction (RT-PCR) and western blotting. In vitro
      invasion of OS cell lines (Saos-2, MG-63) were investigated by the Matrigel
      invasion assay. Mean MMP-9 protein and mRNA expression was significantly
      suppressed; in addition, mean TIMP-1 protein mRNA expression were upregulated by
      increasing GA concentrations. GA reduced the invasiveness of OS cell lines dose
      dependently. Furthermore, specific inhibition of TIMP-1 secretion with siRNA
      against TIMP-1 significantly reduced the effect of GA on OS cell lines. Overall,
      our findings suggest that GA reduces the invasive potential of OS cells via
      attenuation of MMP-9 and upregulation of TIMP-1. Moreover, TIMP-1 played an
      important role in the reduction of invasive potential of the OS cells which were
      treated by GA.

PMID- 23175214
TI  - microRNA and inflammatory gene expression as prognostic marker for overall
      survival in esophageal squamous cell carcinoma.
AB  - MicroRNAs (miRNAs) and inflammatory genes have a role in the initiation and
      development of esophageal squamous cell carcinoma (ESCC). In our study, we
      examined the potential of using miRNA and inflammatory gene expression patterns
      as prognostic classifiers for ESCC. Five miRNAs and 25 inflammatory-related genes
      were measured by quantitative reverse transcriptase PCR in tumor tissues and
      adjacent noncancerous tissues from 178 Chinese patients with ESCC. The expression
      levels of miR-21 (p = 0.027), miR-181b (p = 0.002) and miR-146b (p = 0.021) in
      tumor tissue and miR-21 (p = 0.003) in noncancerous tissue were associated with
      overall survival of patients. These data were combined to generate a miRNA risk
      score that was significantly associated with worse prognosis (p = 0.0001),
      suggesting that these miRNAs may be useful prognostic classifiers for ESCC. To
      construct an inflammatory gene prognostic classifier, we divided the population
      into training (n = 124) and test cohorts (n = 54). The expression levels of
      CRY61, CTGF and IL-18 in tumor tissue and VEGF in adjacent noncancerous tissue
      were modestly associated with prognosis in the training cohort |Z-score| > 1.5
      and were subsequently used to construct a Cox regression-based inflammatory risk
      score (IRS). IRS was significantly associated with survival in both the training
      cohort (p = 0.002) and the test cohort (p = 0.005). Furthermore, Cox regression
      models combining both miRNA risk score and IRS performed significantly better
      than models with either alone (p < 0.001 likelihood ratio test). Therefore, miRNA
      and inflammatory gene expression patterns, alone or in combination, have
      potential as prognostic classifiers for ESCC and may help to guide therapeutic
      decisions.

PMID- 23175215
TI  - Stem cells of the respiratory system: from identification to differentiation into
      functional epithelium.
AB  - We review recent progress in the stem cell biology of the respiratory system, and
      discuss its scientific and translational ramifications. Several studies have
      defined novel stem cells in postnatal lung and airways and implicated their roles
      in tissue homeostasis and repair. In addition, significant advances in the
      generation of respiratory epithelium from pluripotent stem cells (PSCs) now
      provide a novel and powerful platform for understanding lung development,
      modeling pulmonary diseases, and implementing drug screening. Finally,
      breakthroughs have been made in the generation of decellularized lung matrices
      that can serve as a scaffold for repopulation with respiratory cells derived from
      either postnatal or PSCs. These studies are a critical step forward towards the
      still distant goal of stem cell-based regenerative medicine for diseases of lung
      and airways.

PMID- 23175216
TI  - Beam coordinate transformations from DICOM to DOSXYZnrc.
AB  - Digital imaging and communications in medicine (DICOM) format is the de facto
      standard for communications between therapeutic and diagnostic modalities. A plan
      generated by a treatment planning system (TPS) is often exported in DICOM format.
      BEAMnrc/DOSXYZnrc is a widely used Monte Carlo (MC) package for modelling the
      Linac head and simulating dose delivery in radiotherapy. It has its own
      definition of beam orientation, which is not in compliance with the one defined
      in the DICOM standard. MC dose calculations using information from TPS generated
      plans require transformation of beam orientations to the DOSXYZnrc coordinate
      system (c.s.) and the transformation is non-trivial. There have been two studies
      on the coordinate transformations. The transformation equation sets derived have
      been helpful to BEAMnrc/DOSXYZnrc users. However, the transformation equation
      sets are complex mathematically and not easy to program. In this study, we derive
      a new set of transformation equations, which are more compact, easily
      understandable, and easier for computational implementation. The derivation of
      the polar angle theta and the azimuthal angle phi used by DOSXYZnrc is similar to
      the existing studies by applying a series of rotations to a vector in DICOM
      patient c.s. The derivation of the beam rotation phi(col) for DOSXYZnrc, however,
      is different. It is obtained by a direct combination of the actual collimator
      rotation with the projection of the couch rotation to the collimator rotating
      plane. Verification of the transformation has been performed using clinical
      plans. The comparisons between TPS and MC results show very good geometrical
      agreement for field placements, together with good agreement in dose
      distributions.

PMID- 23175217
TI  - Antiviral immunity: Immune control of endogenous retroviruses.

PMID- 23175218
TI  - Regulatory T cells: T(Reg) cells separate the weak from the strong.

PMID- 23175219
TI  - Regulatory T cells: Working on a commitment.

PMID- 23175220
TI  - T cell responses: Jagged gives an edge to T(H)1 cells.

PMID- 23175224
TI  - Signalling: New roles for TLR2.

PMID- 23175229
TI  - NLRC5: a key regulator of MHC class I-dependent immune responses.
AB  - The expression of MHC class I molecules is crucial for the initiation and
      regulation of adaptive immune responses against pathogens. NOD-, LRR- and CARD
      containing 5 (NLRC5) was recently identified as a specific transactivator of MHC
      class I genes (CITA). NLRC5 and the master regulator for MHC class II genes,
      class II transactivator (CIITA), interact with similar MHC promoter-bound
      factors. Here, we provide a broad overview of the molecular mechanisms behind MHC
      class I transcription and the role of the class I transactivator NLRC5 in MHC
      class I-dependent immune responses.

PMID- 23175230
TI  - Functional immunoimaging: the revolution continues.
AB  - Ten years ago, in 2002, the introduction of dynamic in vivo imaging to
      immunologists set a new standard for studying immune responses. In particular,
      two-photon imaging has provided tremendous insights into immune cell dynamics in
      various contexts, including infection, cancer, transplantation and autoimmunity.
      Whereas initial studies were restricted to the migration of and interactions
      between immune cells, recent advances are bringing intravital imaging to a new
      level in which cell dynamics and function can be investigated simultaneously.
      These exciting developments further broaden the applications of immunoimaging and
      provide unprecedented opportunities to probe and decode immune cell communication
      in situ.

PMID- 23175231
TI  - Factors affecting T cell responses induced by fully synthetic glyco-gold
      nanoparticles.
AB  - We have synthesized and characterized nearly monodisperse and highly pure gold
      nanoparticles (2 and 5 nm) coated with non-immunoactive mono- and disaccharides,
      modelled after the capsular polysaccharide of serogroup A of the Neisseria
      meningitidis bacterium. We have used them to test their ability to induce immune
      cell responses as a consequence of their multivalency. The results indicate that
      they are indeed immunoactive and that immunoactivity is strongly dependent on
      size, and larger, 5 nm nanoparticles perform far better than smaller, 2 nm ones.
      Immune response (activation of macrophages) initiates with the whole nanoparticle
      recognition by the surface of antigen-presenting cells, independent of the
      saccharide oligomerization (or charge) on the nanoparticle surface. The induction
      of T cell proliferation and the increase of IL-2 levels, a consequence of the
      expression of MHC II involved in antigen presentation, require the presence of a
      disaccharide on the nanoparticle, not just a monosaccharide. A possible
      explanation is that, at this stage, the saccharides are detached from the gold
      surface. These results may provide leads for designing new saccharide-based,
      nanoparticle-conjugate vaccines.

PMID- 23175232
TI  - Sal-like protein 4 (SALL4), a stem cell biomarker in liver cancers.
AB  - Liver cancers, including hepatocellular carcinomas (HCCs), cholangiocarcinomas
      (CCs), and fibrolamellar HCCs (FL-HCCs) are among the most common cancers
      worldwide and are associated with a poor prognosis. Investigations of genes
      important in liver cancers have focused on Sal-like protein 4 (SALL4), a member
      of a family of zinc finger transcription factors. It is a regulator of
      embryogenesis, organogenesis, pluripotency, can elicit reprogramming of somatic
      cells, and is a marker of stem cells. We found it expressed in normal murine
      hepatoblasts, normal human hepatic stem cells, hepatoblasts and biliary tree stem
      cells, but not in mature parenchymal cells of liver or biliary tree. It was
      strongly expressed in surgical specimens of human HCCs, CCs, a combined
      hepatocellular and cholangiocarcinoma, a FL-HCC, and in derivative,
      transplantable tumor lines in immune-compromised hosts. Bioinformatics analyses
      indicated that elevated expression of SALL4 in tumors is associated with poor
      survival of HCC patients. Experimental manipulation of SALL4's expression results
      in changes in proliferation versus differentiation in human HCC cell lines in
      vitro and in vivo in immune-compromised hosts. Virus-mediated gene transfer of
      SALL4 was used for gain- and loss-of-function analyses in the cell lines.
      Significant growth inhibition in vitro and in vivo, accompanied by an increase in
      differentiation occurred with down-regulation of SALL4. Overexpression of SALL4
      resulted in increased cell proliferation in vitro, correlating with an increase
      in expression of cytokeratin19 (CK19), epithelial cell adhesion molecules
      (EpCAM), and adenosine triphosphate (ATP)-binding cassette-G2 (ABCG2).
      CONCLUSION: SALL4's expression is an indicator of stem cells, a prognostic marker
      in liver cancers, correlates with cell and tumor growth, with resistance to 5-FU,
      and its suppression results in differentiation and slowed tumor growth. SALL4 is
      a novel therapeutic target for liver cancers.

PMID- 23175233
TI  - Glycobioinformatics: current strategies and tools for data mining in MS-based
      glycoproteomics.
AB  - Glycobioinformatics is a rapidly developing field providing a vital support for
      MS-based glycoproteomics research. Recent advances in MS greatly increased
      technological capabilities for high throughput glycopeptide analysis. However,
      interpreting MS output, in terms of identifying glycan structures, attachment
      sites and glycosylation linkages still presents multiple challenges. Here, we
      discuss current strategies used in MS-based glycoproteomics and bioinformatics
      tools available for MS-based glycopeptide and glycan analysis. We also provide a
      brief overview of recent efforts in glycobioinformatics such as the new
      initiative UniCarbKB directed toward developing more comprehensive and unified
      glycobioinformatics platforms. With regards to glycobioinformatics tools and
      applications, we do not express our personal preferences or biases, but rather
      focus on providing a concise description of main features and functionalities of
      each application with the goal of assisting readers in making their own choices
      and identifying and locating glycobioinformatics tools most suitable for
      achieving their experimental objectives.

PMID- 23175234
TI  - Risk factors for major morbidity after liver resection for hepatocellular
      carcinoma.
AB  - BACKGROUND: Bile leakage, and organ and/or space surgical-site infection (SSI)
      are common causes of major morbidity after partial hepatectomy for hepatocellular
      carcinoma (HCC). The purpose of this study was to analyse risk factors for major
      morbidity and to explore strategies for its reduction after partial hepatectomy
      for HCC. METHODS: Risk factors for bile leakage and organ/space SSI were analysed
      in patients who underwent partial hepatectomy for HCC between 2001 and 2010. The
      causes, management and outcomes of intractable bile leakage requiring endoscopic
      therapy or percutaneous transhepatic biliary drainage were analysed. In addition,
      causative bacteria, outcomes and characteristics of organ/space SSI were
      investigated. Risk factors were identified using multivariable analysis. RESULTS:
      Some 359 patients were included in the analysis. The prevalence of bile leakage
      and organ/space SSI was 12.8 and 8.6 per cent respectively. Repeat hepatectomy
      and an operating time of at least 300 min were identified as independent risk
      factors for bile leakage. The main causes of intractable bile leakage were latent
      strictures of the biliary system caused by previous treatments for HCC and
      intraoperative injury of the hepatic duct during repeat hepatectomy. Independent
      risk factors for organ/space SSI were repeat hepatectomy and bile leakage.
      Methicillin-resistant Staphylococcus aureus was detected more frequently in
      organ/space SSI after repeat hepatectomy than after initial partial hepatectomy.
      CONCLUSION: Repeat hepatectomy and prolonged surgery were identified as risk
      factors for bile leakage after liver resection for HCC. Bile leakage and repeat
      hepatectomy increased the risk of organ/space SSI.

PMID- 23175235
TI  - PICVib: an accurate, fast, and simple procedure to investigate selected
      vibrational modes at high theoretical levels.
AB  - A new approach Procedure for Investigating Categories of Vibrations (PICVib) for
      estimating vibrational frequencies of selected modes using only the structure and
      energy calculations at a more demanding computational level is presented and
      explored. The PICVib has an excellent performance at only a small fraction of the
      computational demand required for a complete analytical calculation. The errors
      are smaller than ca. 0.5% when DFT functionals are combined with high level ab
      initio methods. The approach is general because it can use any quantum chemical
      program and electronic structure method. It is very robust because it was
      validated for a wide range of frequency values (ca. 20-4800 cm(-1)) and systems:
      XH(3) (D(3h) ) with X = B, Al, Ga, N, P, As, O, S, and Se, YH(4) (D(4h) ) with Y
      = C, Si, and Ge, conformers of RDX, S(N) 2 and E2 reactions,
      [W(dppe)(2)(NNC(5)H(10))] complex, carbon nanotubes, and hydrogen-bonded
      complexes including guanine-cytosine pair.

PMID- 23175236
TI  - [Assessment inventories for hearing aid outcome].
AB  - BACKGROUND: At the beginning of 2012 new fee schedule positions have been
      introduced to the ambulatory physician fee schedule ("Einheitlicher
      Bewertungsmabetastab", EBM) regarding the hearing aid fittings of youngsters and
      adults. With regards to quality assurance the use of a hearing aid outcome self
      assessment inventory is made compulsive. This article aims to review available
      hearing aid (self-) assessment inventories as well as the evaluations regarding
      criteria for test quality implemented. METHOD: For this systematic review a
      selective literature research in PubMed has been carried out. RESULTS: There are
      various self assessment inventories measuring hearing aid benefit. Many of the
      studies evaluating these inventories were implemented during the 1980ies and
      early 90ies when analogue hearing aids were commonly used. These results cannot
      automatically be transferred to the nowadays common digital devices. Only a small
      amount of studies investigated German translations of the mostly originally
      English inventories. DISCUSSION: In order to be able to identify the actual
      meaning of resulting values from these inventories, it is important for ENT
      doctors and audiologists to be well informed of the tests' quality criteria.

PMID- 23175237
TI  - MicroRNA-27a inhibitors alone or in combination with perifosine suppress the
      growth of gastric cancer cells.
AB  - MicroRNA-27a (miR-27a) is an oncogene that contributes to drug resistance in
      various types of cancer. However, the involvement of miR-27a in gastric cancer
      has yet to be elucidated. Perifosine is an alkylphospholipid exhibiting antitumor
      activity as shown in both preclinical studies and clinical trials. The effects of
      perifosine on gastric cancer have yet to be determined. Therefore, this study was
      conducted to detect the role of miR-27a and perifosine in human gastric cancer.
      miR-27a was found to be expressed in human gastric cancer tissues and cell lines
      by quantitative reverse-transcription polymerase chain reaction (qRT-PCR). The
      correlation between miR-27a expression and clinicopathological characteristics of
      gastric cancer. We also explored the growth inhibitory effect of perifosine on
      human gastric cancer cells with or without co-targeting miR-27a by sulforhodamine
      B (SRB) assay. The results showed that miR-27a expression was significantly
      upregulated in gastric cancer tissues, compared with their non-tumor adjacent
      tissues. High expression levels of miR-27a were associated with poor tumor
      histological grade (P=0.037). MiR-27a inhibitors suppressed the growth of MGC-803
      cells. Assay results showed that perifosine exerted its activity selectively on
      the AGS cell line and the growth inhibitory effect of perifosine was enhanced
      significantly in combination with miR-27a inhibitors in MGC-803 cells. In
      conclusion, our results demonstrated that miR-27a may be a therapeutic target and
      potential prognostic biological marker in gastric cancer. MiR-27a inhibitors
      alone or in combination with perifosine may be a novel therapeutic approach
      against gastric cancer.

PMID- 23175238
TI  - Considering the needs of English language learner populations: an examination of
      the population validity of reading intervention research.
AB  - This article synthesizes reading intervention research studies intended for use
      with struggling or at-risk students to determine which studies adequately address
      population validity, particularly in regard to the diverse reading needs of
      English language learners. An extensive search of the professional literature
      between 2001 and 2010 yielded a total of 67 reading intervention studies
      targeting at-risk elementary students. Findings revealed that many current
      research studies fail to adequately describe the sample, including the accessible
      and target populations, and to disaggregate their findings based on demographic
      characteristics. When population validity issues are not addressed, researchers
      cannot generalize findings to other populations of students, and it becomes
      unclear what intervention strategies work, especially with English language
      learner student populations. However, 25 studies did specifically recognize and
      address the needs of English language learners, indicating more researchers are
      taking into consideration the diverse needs of other struggling student
      populations. 

PMID- 23175239
TI  - Presence of entomobirnaviruses in Chinese mosquitoes in the absence of Dengue
      virus co-infection.
AB  - Birnaviruses, including the genus Entomobirnavirus, are socio-economically
      important viruses. Currently, only Drosophila X virus has been formally assigned
      to the genus Entomobirnavirus, but two more viruses were recently isolated,
      Espirito Santo virus (ESV) and Culex Y virus. The host mosquito has been reported
      to carry many viruses, but seldom entomobirnaviruses. To discover potential
      pathogens in mosquitoes, we exploited small-RNAs high-throughput sequencing of
      three mosquito species caught in South China. A virus that genetically likes
      entomobirnavirus, Mosquito X virus (MXV), was identified from Anopheles sinensis
      and was 97% identical to ESV, which co-infects with Dengue virus (DENV). However,
      the absence of DENV in the A. sinensis suggested the independence of MXV
      infection from dengue co-infection. Our discovery complements prior research on
      entomobirnaviruses and proved that MXV may be widespread in mosquitoes on
      different continents. This work also highlights the applying of high-throughput
      sequencing of small RNAs to survey viruses carried by insect vectors.

PMID- 23175241
TI  - Characterization of naturally Epstein-Barr virus-infected gastric carcinoma cell
      line YCCEL1.
AB  - Epstein-Barr virus (EBV) is a herpesvirus associated with lymphomas and
      carcinomas. While EBV-associated epithelial cell lines are good model systems to
      investigate the role of EBV in carcinoma, only a few cell lines are available as
      they are hard to acquire. A greater variety of naturally EBV-infected cell lines
      which are derived from tumour patients are needed to represent various features
      of EBVaGC. We characterized cell line YCCEL1, established from a Korean EBVaGC
      patient, to ascertain whether it can be used to study the roles of EBV in EBVaGC.
      The expression of EBV genes and cell surface markers was examined by in situ
      hybridization, RT-PCR, Western blot analysis, immunofluorescence assay and
      Northern blot analysis. EBV episomal status was analysed by Southern blotting and
      real-time PCR. This cell line expressed EBV nuclear antigen 1 (EBNA1) and latent
      membrane protein 2A (LMP2A), but not EBNA2, LMP2B nor LMP1. The majority of the
      lytic proteins were not detected in YCCEL1 cells either before or after treatment
      with 12-O-tetradecanoylphorbol-13-acetate. YCCEL1 cells expressed BART microRNAs
      (miRNAs) at high level but did not express BHRF1 miRNAs. YCCEL1 cells expressed
      cytokeratin, but not CD21 and CD19, suggesting CD21-independent EBV infection.
      The latent EBV gene and EBV miRNA expression pattern of YCCEL1 cells closely
      resembled that of general EBVaGC cases. Our results support the value of YCCEL1
      cells as a good model system to study the role of EBV in gastric carcinogenesis.

PMID- 23175240
TI  - Genetic characterization by composite sequence analysis of a new pathogenic field
      strain of equine infectious anemia virus from the 2006 outbreak in Ireland.
AB  - Equine infectious anemia virus (EIAV), the causative agent of equine infectious
      anaemia (EIA), possesses the least-complex genomic organization of any known
      extant lentivirus. Despite this relative genetic simplicity, all of the complete
      genomic sequences published to date are derived from just two viruses, namely the
      North American EIAV(WYOMING) (EIAV(WY)) and Chinese EIAV(LIAONING) (EIAV(LIA))
      strains. In 2006, an outbreak of EIA occurred in Ireland, apparently as a result
      of the importation of contaminated horse plasma from Italy and subsequent
      iatrogenic transmission to foals. This EIA outbreak was characterized by cases of
      severe, sometimes fatal, disease. To begin to understand the molecular mechanisms
      underlying this pathogenic phenotype, complete proviral genomic sequences in the
      form of 12 overlapping PCR-generated fragments were obtained from four of the
      EIAV-infected animals, including two of the index cases. Sequence analysis of
      multiple molecular clones produced from each fragment demonstrated the extent of
      diversity within individual viral genes and permitted construction of consensus
      whole-genome sequences for each of the four viral isolates. In addition, complete
      env gene sequences were obtained from 11 animals with differing clinical
      profiles, despite exposure to a common EIAV source. Although the overall genomic
      organization of the Irish EIAV isolates was typical of that seen in all other
      strains, the European viruses possessed <=80 % nucleotide sequence identity with
      either EIAV(WY) or EIAV(LIA). Furthermore, phylogenetic analysis suggested that
      the Irish EIAV isolates developed independently of the North American and Chinese
      viruses and that they constitute a separate monophyletic group.

PMID- 23175242
TI  - New models of hepatitis E virus replication in human and porcine hepatocyte cell
      lines.
AB  - Hepatitis E virus (HEV) causes acute, enterically transmitted hepatitis in human.
      It is associated with large epidemics in tropical and subtropical regions where
      it is endemic or with sporadic cases in non-endemic regions. Unlike other
      hepatitis viruses, HEV has several animal reservoirs. Phylogenetic studies on HEV
      human and animal sequences, and the identification of cases of direct
      transmission from animal to human strongly suggest that HEV is a zoonotic agent.
      The lack of efficient cell culture models limits studies on molecular and
      cellular aspects of HEV infection and species barrier crossing. The present study
      reports on the development of two new in vitro models of HEV replication using a
      human hepatoma-derived cell line, HepaRG, and a porcine embryonic stem cell
      derived cell line, PICM-19. These two cell lines have morphological and
      functional properties similar to primary hepatocytes. These in vitro culture
      systems support HEV replication and release of encapsidated RNA. These new models
      represent a powerful tool for studying the viral replication cycle, species
      barrier crossing and virulence factors.

PMID- 23175243
TI  - Tumor vessel-injuring ability improves antitumor effect of cytotoxic T
      lymphocytes in adoptive immunotherapy.
AB  - Angiogenesis is required for normal physiologic processes, but it is also
      involved in tumor growth, progression and metastasis. Here, we report the
      development of an immune-based antiangiogenic strategy based on the generation of
      T lymphocytes that possess killing specificity for cells expressing vascular
      endothelial growth factor receptor 2 (VEGFR2). To target VEGFR2-expressing cells,
      we engineered cytotoxic T lymphocyte (CTL) expressing chimeric T-cell receptors
      (cTCR-CTL) comprised of a single-chain variable fragment (scFv) against VEGFR2
      linked to an intracellular signaling sequence derived from the CD3zeta chain of
      the TCR and CD28 by retroviral gene transduction methods. The cTCR-CTL exhibited
      efficient killing specificity against VEGFR2 and a tumor-targeting function in
      vitro and in vivo. Reflecting such abilities, we confirmed that the cTCR-CTL
      strongly inhibited the growth of a variety of syngeneic tumors after adoptive
      transfer into tumor-bearing mice without consequent damage to normal tissue. In
      addition, CTL expressing both cTCR and tumor-specific TCR induced complete tumor
      regression due to enhanced tumor infiltration by the CTL and long-term antigen
      specific function. These findings provide evidence that the tumor vessel-injuring
      ability improved the antitumor effect of CTLs in adoptive immunotherapy for a
      broad range of cancers by inducing immune-mediated destruction of the tumor
      neovasculature.

PMID- 23175244
TI  - Radiosensitivity by ING4-IL-24 bicistronic adenovirus-mediated gene cotransfer on
      human breast cancer cells.
AB  - Breast cancer is a common malignancy among women and is associated with poor 5
      year survival rates. Gene radiotherapy, that is, gene therapy combined with
      radiotherapy, has been extensively studied as a new mode of therapy, but most
      studies have assessed only one gene. Here, we inserted two anti-oncogenes, ING4
      (inhibitor of growth family member 4) and interleukin-24 (IL-24), in the same
      bicistronic adenovirus vector and explored the effect of dual-gene therapy
      combined with radiotherapy on breast cancer cells. Flow cytometry assays showed
      that adenovirus-mediated ING4 and IL-24 expression could suppress growth, promote
      apoptosis and induce G2/M cell-cycle arrest in MDA-MB-231 cells. Moreover, animal
      model studies demonstrated that the combination of ING4/IL-24 gene therapy and
      radiotherapy significantly suppressed cell proliferation and inhibited tumor
      growth (P<0.05). Mechanistically, the pro-apoptotic response likely involved the
      upregulation of Bax and Caspase-3 and the downregulation of Bcl-2. Thus, this
      study indicates that the co-expression of the two anti-oncogenes, ING4 and IL-24,
      could significantly promote radiotherapy sensitivity in MDA-MB-231 breast cancer
      cells.

PMID- 23175245
TI  - A review of the role of Puma, Noxa and Bim in the tumorigenesis, therapy and drug
      resistance of chronic lymphocytic leukemia.
AB  - Chronic lymphocytic leukemia (CLL) is the most common leukemia in adults in the
      Western countries. The entire pathogenesis of CLL is not clear now, but defective
      regulation of apoptosis seems to be more important than uncontrolled cell
      proliferation in CLL. There are two main pathways of apoptosis: the extrinsic
      pathway and the intrinsic pathway. It is worth noting that the intrinsic pathway,
      rather than the extrinsic pathway, appears to be the key mediator of impaired
      apoptosis in CLL as a result of B-cell lymphoma 2 (Bcl-2) upregulation. One
      subclass of pro-apoptotic members within the Bcl-2 family are Bcl-2 homology 3
      (BH3)-only proteins. They can regulate directly and/or indirectly the remaining
      Bcl-2 proteins to endanger mitochondria and induce apoptosis. We chose three
      molecules from the BH3-only family, Puma, Noxa and Bim, respectively, which had
      shown an exciting antitumor potential in previous reports, to explore their
      characters and functions in tumorigenesis, therapy and drug resistance of CLL.

PMID- 23175246
TI  - Rhodium-catalyzed cysteine modification with diazo reagents.
AB  - A simple rhodium(II) complex catalyzes cysteine modification with diazo reagents.
      The reaction is marked by clean cysteine selectivity and mild reaction
      conditions. The resulting linkage is significantly more stable in human plasma
      serum, when compared to common maleimide reagents.

PMID- 23175247
TI  - Microbiology of explanted suture segments from infected and noninfected surgical
      patients.
AB  - Sutures under selective host/environmental factors can potentiate postoperative
      surgical site infection (SSI). The present investigation characterized microbial
      recovery and biofilm formation from explanted absorbable (AB) and nonabsorbable
      (NAB) sutures from infected and noninfected sites. AB and NAB sutures were
      harvested from noninfected (70.9%) and infected (29.1%) sites in 158 patients. At
      explantation, devices were sonicated and processed for qualitative/quantitative
      bacteriology; selective sutures were processed for scanning electron microscopy
      (SEM). Bacteria were recovered from 85 (53.8%) explanted sites; 39 sites were
      noninfected, and 46 were infected. Suture recovery ranged from 11.1 to 574.6 days
      postinsertion. A significant difference in mean microbial recovery between
      noninfected (1.2 isolates) and infected (2.7 isolates) devices (P < 0.05) was
      noted. Staphylococcus epidermidis, Staphylococcus aureus, coagulase-negative
      staphylococci (CNS), Peptostreptococcus spp., Bacteroides fragilis, Escherichia
      coli, Enterococcus spp., Pseudomonas aeruginosa, and Serratia spp. were recovered
      from infected devices, while commensal skin flora was recovered from noninfected
      devices. No significant difference in quantitative microbial recovery between
      infected monofilament and multifilament sutures was noted. Biofilm was present in
      100% and 66.6% of infected and noninfected devices, respectively (P < 0.042). We
      conclude that both monofilament and braided sutures provide a hospitable surface
      for microbial adherence: (i) a significant difference in microbial recovery from
      infected and noninfected sutures was noted, (ii) infected sutures harbored a
      mixed flora, including multidrug-resistant health care-associated pathogens, and
      (iii) a significant difference in the presence or absence of a biofilm in
      infected versus noninfected explanted devices was noted. Further studies to
      document the benefit of focused risk reduction strategies to minimize suture
      contamination and biofilm formation postimplantation are warranted.

PMID- 23175248
TI  - First clinical cases of OXA-48-producing carbapenem-resistant Klebsiella
      pneumoniae in the United States: the "menace" arrives in the new world.
AB  - OXA-48 has emerged as a major carbapenemase associated with the
      Enterobacteriaceae in Europe, North Africa, and Asia. We report the first two
      clinical cases of OXA-48-type carbapenemase-producing Enterobacteriaceae in the
      United States from patients recently hospitalized in Saudi Arabia and India. Each
      is more carbapenem resistant than nearly all previously reported OXA-48-type
      producing Enterobacteriaceae.

PMID- 23175249
TI  - Mycobacterial interspersed repetitive-unit-variable-number tandem-repeat (MIRU
      VNTR) genotyping of mycobacterium intracellulare for strain comparison with
      establishment of a PCR-based database.
AB  - Strain comparison is important to population genetics and to evaluate relapses in
      patients with Mycobacterium avium complex (MAC) lung disease, but the "gold
      standard" of pulsed-field gel electrophoresis (PFGE) is time-consuming and
      complex. We used variable-number tandem repeats (VNTR) for fingerprinting of
      respiratory isolates of M. intracellulare from patients with underlying
      bronchiectasis, to establish a nonsequence-based database for population
      analysis. Different genotypes identified by PFGE underwent species identification
      using a 16S rRNA gene multiplex PCR. Genotypes of M. intracellulare were
      confirmed by internal transcribed spacer 1 (ITS1) sequencing and characterized
      using seven VNTR primers. The pattern of VNTR amplicon sizes and repeat number
      defined each specific VNTR type. Forty-two VNTR types were identified among 84
      genotypes. PFGE revealed most isolates with the same VNTR type to be clonal or
      exhibit similar grouping of bands. Repetitive sequence-based PCR (rep-PCR) showed
      minimal pattern diversity between VNTR types compared to PFGE. Fingerprinting of
      relapse isolates from 31 treated patients using VNTR combined with 16S multiplex
      PCR unambiguously and reliably distinguished different genotypes from the same
      patient, with results comparable to those of PFGE. VNTR for strain comparison is
      easier and faster than PFGE, is as accurate as PFGE, and does not require
      sequencing. Starting with a collection of 167 M. intracellulare isolates, VNTR
      distinguished M. intracellulare into 42 clonal groups. Comparison of isolates
      from different geographic areas, habitats, and clinical settings is now possible.

PMID- 23175250
TI  - Seroepidemiological evidence of avian influenza A virus transmission to pigs in
      southern China.
AB  - Recently, three novel avian-origin swine influenza viruses (SIVs) were first
      isolated from pigs in Guangdong Province, southern China, yet little is known
      about the seroprevalence of avian influenza viruses among pigs in southern China.
      Here, we report for the first time the seroprevalence of avian H3, H4, and H6
      influenza viruses in swine populations and the lack of seroepidemiological
      evidence of avian H5 influenza virus transmission to pigs in China.

PMID- 23175251
TI  - Occurrence of norovirus infections in asymptomatic food handlers in South Korea.
AB  - Prevalence of asymptomatic norovirus infection was investigated in food handlers
      in South Korea. Among 6,441 subjects, 66 (1.02%) had norovirus infections
      confirmed by reverse transcription (RT)-PCR (real time and nested). GII-12 and
      GII-4 were the prevalent genotypes. Our data suggest that infection of
      asymptomatic food handlers is an important transmission source in norovirus
      outbreaks.

PMID- 23175252
TI  - Interlaboratory and interstudy reproducibility of a novel lateral-flow device and
      influence of antifungal therapy on detection of invasive pulmonary aspergillosis.
AB  - Interest in lateral-flow devices (LFDs) as potential point-of-care assays for the
      diagnosis of infectious diseases has increased. Our objective was to evaluate the
      interlaboratory and interstudy reproducibility and the effects of antifungal
      therapy on an LFD developed for invasive pulmonary aspergillosis (IPA) detection.
      An established neutropenic guinea pig model of IPA caused by Aspergillus
      fumigatus was used. At predetermined time points (1 h and 3, 5, and 7 days
      postinoculation), blood and bronchoalveolar lavage (BAL) fluid were collected
      from infected and uninfected animals. In a separate experiment, guinea pigs were
      treated with posaconazole (10 mg/kg of body weight orally [p.o.] twice a day
      [BID]), voriconazole (10 mg/kg p.o. BID), liposomal amphotericin B (10 mg/kg
      intraperitoneally [i.p.] once a day [QD]), or caspofungin (2 mg/kg i.p. QD), and
      samples were collected on days 7 and 11. Each laboratory independently evaluated
      the IgG monoclonal antibody-based LFD. Galactomannan and (1 -> 3)-beta-D-glucan
      were also measured using commercially available kits. Good interlaboratory
      agreement was observed with the LFD, as the results for 97% (32/33) of the serum
      and 78.8% (26/33) of the BAL fluid samples from infected animals were in
      agreement. Good interstudy agreement was also observed. The serum sensitivity of
      each surrogate-marker assay was reduced in animals treated with antifungals. In
      contrast, these markers remained elevated within the BAL fluids of treated
      animals, which was consistent with the fungal burden and histopathology results.
      These results demonstrate that the LFD assay is reproducible between different
      laboratories and studies. However, the sensitivity of this assay and other
      markers of IPA may be reduced with serum in the presence of antifungal therapy.

PMID- 23175253
TI  - Pulsed-field gel electrophoresis analysis of Bordetella pertussis isolates
      circulating in Europe from 1998 to 2009.
AB  - Between 1998 and 2009, Bordetella pertussis clinical isolates were collected
      during three periods, i.e., 1998 to 2001 (n = 102), 2004 to 2005 (n = 154), and
      2007 to 2009 (n = 140), from nine countries with distinct vaccination programs,
      i.e., Denmark, Finland, France, Germany, The Netherlands, Norway, Poland, Sweden,
      and the United Kingdom. Pulsed-field gel electrophoresis (PFGE) analysis was
      performed according to standardized recommendations for epidemiological typing of
      B. pertussis. There were 81 different PFGE profiles, five of which (BpSR3, BpSR5,
      BpSR10, BpSR11, and BpSR12) were observed in 61% of the 396 isolates and shown to
      be predominant in almost all countries. The major profile, BpSR11, showed a
      decreasing trend from 25% to 30% in 1998 to 2005 to 13% in 2007 to 2009, and
      there were increases in BpSR3 and BpSR10 from 0% and 8% to 21% and 22%,
      respectively. One difference between these profiles is that BpSR11 contains
      isolates harboring the fim3-2 allele and BpSR3 and BpSR10 contain isolates
      harboring the fim3-1 allele. The total proportion of the five predominant
      profiles increased from 44% in 1998 to 2001 to 63% in 2004 to 2005 to 70% in 2007
      to 2009. In conclusion, common PFGE profiles were identified in B. pertussis
      populations circulating in European countries with different vaccination programs
      and different vaccine coverages. These prevalent isolates contain the novel
      pertussis toxin promoter ptxP3 allele. However, there is evidence for
      diversifying selection between ptxP3 strains characterized by distinct PFGE
      profiles. This work shows that, even within a relatively short time span of 10
      years, successful isolates which spread through Europe and cause large shifts in
      B. pertussis populations may emerge.

PMID- 23175254
TI  - Influence of different media, incubation times, and temperatures for determining
      the MICs of seven antifungal agents against Paracoccidioides brasiliensis by
      microdilution.
AB  - MIC assays with Paracoccidioides brasiliensis, the etiological agent of
      paracoccidioidomycosis, had been conducted with variable protocols, employing
      both macrodilution and microdilution tests and including differences in inoculum
      preparation, media used, incubation periods, and temperatures. Twenty-one
      clinical and environmental isolates of Paracoccidioides were tested using
      amphotericin B, itraconazole, ketoconazole, fluconazole, sulfamethoxazole,
      sulfamethoxazole-trimethoprim, and terbinafine, according to the National
      Committee for Clinical Laboratory Standards (National Committee for Clinical
      Laboratory Standards, document M27-A2, 2002), with modifications such as three
      medium formulations (RPMI 1640 medium, McVeigh and Morton [MVM] medium, and
      modified Mueller-Hinton [MMH] medium), two incubation temperatures (room
      temperature [25 to 28  degrees C] and 37  degrees C), and three incubation
      periods (7, 10, and 15 days). The antifungal activities were also classified as
      fungicidal or fungistatic. The best results were obtained after 15 days of
      incubation, which was chosen as the standard incubation time. The MICs for most
      individual isolates grown for the same length of time at the same temperature
      varied with the different media used (P < 0.05). Of the isolates, 81% showed
      transition from the yeast to the mycelial form in RPMI 1640 medium at 37  degrees
      C, independent of the presence of antifungals. MMH medium appears to be a
      suitable medium for susceptibility testing of antifungal drugs with P.
      brasiliensis, except for sulfamethoxazole and the combination of sulfamethoxazole
      trimethoprim, for which the MVM medium yielded better results. The incubation
      temperature influenced the MICs, with, in general, higher MICs at 25  degrees C
      (mycelial form) than at 37  degrees C (P < 0.05). Based on our results, we
      tentatively propose a microdilution assay protocol for susceptibility testing of
      antifungal drugs against Paracoccidioides.

PMID- 23175255
TI  - Simultaneous detection, genotyping, and quantification of human papillomaviruses
      by multicolor real-time PCR and melting curve analysis.
AB  - Long-term infection with high-risk human papillomavirus (HPV) is the leading
      cause of cervical cancer, while infection with low-risk HPV is the major reason
      for condylomata acuminata. An accurate, rapid, and convenient assay that is able
      to simultaneously detect, genotype, and quantify HPV would be of great clinical
      value yet remains to be achieved. We developed a three-color real-time PCR assay
      that is able to analyze 30 predominant HPV types in three reactions. The
      amplification curves indicated the presence of HPV, melting curve analysis
      identified the HPV genotype, and the quantification cycle value determined the
      quantity. We applied this assay to 647 cervical swab samples, and the results
      were compared with those obtained with a commercial genotyping system. The
      proposed assay had a limit of detection of 5 to 50 copies per reaction and a
      dynamic range of 5 * 10(1) to 5 * 10(6) copies per reaction. A comparison study
      showed that the overall sample concordance with the comparison method was 91.6%
      and the type agreement was greater than 98.7%. The quantification study
      demonstrated that the loads of HPV type 16 in 30 samples with cervical
      intraepithelial neoplasia grade III (CIN III) lesions were significantly higher
      than those in samples with CIN I lesions or CIN II lesions, and the results were
      concordant with those of the comparison method. The increased information
      content, high throughput, and low cost would facilitate the use of this real-time
      PCR-based assay in a variety of clinical settings.

PMID- 23175256
TI  - Optimization of a combined human parechovirus-enterovirus real-time reverse
      transcription-PCR assay and evaluation of a new parechovirus 3-specific assay for
      cerebrospinal fluid specimen testing.
AB  - Human parechoviruses (HPeVs), particularly type 3 (HPeV3), are known central
      nervous system (CNS) pathogens, causing serious infections in infants similar to
      those caused by enteroviruses (EVs). The primary aim of this study was to combine
      and validate HPeV and EV real-time reverse transcription-PCR (RT-PCR) detection
      assays with the best available RT-PCR reagents and conditions for parallel
      detection of HPeV and EV on a single platform. The secondary aim was to develop
      and validate a newly developed HPeV3-specific real-time RT-PCR assay. Five
      commercially available RT-PCR kits were evaluated with the pan-HPeV and EV assays
      in one-step and two-step RT-PCRs. Two-step RT-PCR with the AgPath ID RT-PCR (AGP)
      kit performed best for both pan-HPeV and EV assays. The pan-HPeV-specific assay
      performed best with the AGP kit in a one-step RT-PCR. Frozen aliquots of 145 (for
      HPeV, n = 70; for EV, n = 75) previously characterized cerebrospinal fluid (CSF)
      specimens were tested by EV-, pan-HPeV-, and HPeV3-specific (HPeV specimens only)
      assays. The pan-HPeV and EV assays demonstrated 100% analytical sensitivity and
      specificity compared to historic results, while the HPeV3-specific assay
      demonstrated 97% sensitivity and 100% specificity. We propose a real-time pan
      HPeV, EV two-step RT-PCR algorithm for simultaneous detection of HPeV and EV from
      CSF specimens on a single platform. The HPeV3-specific one-step RT-PCR assay can
      be used as a rapid and cost-effective assay to detect and identify HPeV3 in pan
      HPeV RT-PCR assay-positive CSF specimens.

PMID- 23175257
TI  - Typing of nosocomial outbreaks of Acinetobacter baumannii by use of matrix
      assisted laser desorption ionization-time of flight mass spectrometry.
AB  - Matrix-assisted laser desorption ionization-time of flight mass spectrometry
      (MALDI-TOF MS) has been evaluated for the identification of multidrug-resistant
      Acinetobacter baumannii nosocomial outbreaks in comparison with the repetitive
      sequence-based PCR DiversiLab system. The results suggest that MALDI-TOF MS can
      be used for real-time detection of Acinetobacter outbreaks before results from
      DNA-based systems are available.

PMID- 23175258
TI  - Factors influencing the sensitivity and specificity of conventional sequencing in
      human immunodeficiency virus type 1 tropism testing.
AB  - Human immunodeficiency virus type 1 (HIV-1) V3 loop sequence can be used to infer
      viral coreceptor use. The effect of input copy number on population-based
      sequencing of the V3 loop of HIV-1 was examined through replicate deep and
      population-based sequencing of samples with known tropism, a heterogeneous
      clinical sample (624 population-based sequences and 47 deep-sequencing
      replicates), and a large cohort of clinical samples from phase III clinical
      trials of maraviroc including the MOTIVATE/A4001029 studies (n = 1,521). Proviral
      DNA from two independent samples from each of 101 patients from the
      MOTIVATE/A4001029 studies was also analyzed. Cumulative technical error occurred
      at a rate of 3 * 10(-4) mismatches/bp, without observed effect on inferred
      tropism. Increasing PCR replication increased minority species detection with an
      ~10% minority population detected in 18% of cases using a single replicate at a
      viral load of 1,072 copies/ml and in 44% of cases using three replicates. The
      nucleotide prevalence detected by population-based and deep sequencing were
      highly correlated (Spearman's rho, 0.73), and the accuracy increased with
      increasing input copy number (P < 0.001). Triplicate sequencing was able to
      predict tropism changes in the MOTIVATE/A4001029 studies for both low (P = 0.05)
      and high (P = 0.02) viral loads. Sequences derived from independently extracted
      and processed samples of proviral DNA for the same patient were equivalent to
      replicates from the same extraction (P = 0.45) and had correlated position
      specific scoring matrix scores (Spearman's rho, 0.75; P << 0.001); however,
      concordance in tropism inference was only 83%. Input copy number and PCR
      replication are important factors in minority species detection in samples with
      significant heterogeneity.

PMID- 23175259
TI  - Rapid whole-genome sequencing for investigation of a suspected tuberculosis
      outbreak.
AB  - Two Southeast Asian students attending the same school in the United Kingdom
      presented with pulmonary tuberculosis. An epidemiological investigation failed to
      link the two cases, and drug resistance profiles of the Mycobacterium
      tuberculosis isolates were discrepant. Whole-genome sequencing of the isolates
      found them to be genetically identical, suggesting a missed transmission event.

PMID- 23175260
TI  - Rapid detection of Panton-Valentine leukocidin in Staphylococcus aureus cultures
      by use of a lateral flow assay based on monoclonal antibodies.
AB  - Panton-Valentine leukocidin (PVL) is a virulence factor of Staphylococcus aureus,
      which is associated with skin and soft-tissue infections and necrotizing
      pneumonia. To develop a rapid phenotypic assay, recombinant PVL F component was
      used to generate monoclonal antibodies by phage display. These antibodies were
      spotted on protein microarrays and screened using different lukF-PV preparations
      and detection antibodies. This led to the identification of the optimal antibody
      combination that was then used to establish a lateral flow assay. This test was
      used to detect PVL in S. aureus cultures. The detection limit of the assay with
      purified native and recombinant antigens was determined to be around 1 ng/ml.
      Overnight cultures from various solid and liquid media proved suitable for PVL
      detection. Six hundred strains and clinical isolates from patients from America,
      Europe, Australia, Africa, and the Middle East were tested. Isolates were
      genotyped in parallel by DNA microarray hybridization for confirmation of PVL
      status and assignment to clonal complexes. The sensitivity, specificity, and
      positive and negative predictive values of the assay in this trial were 99.7,
      98.3, 98.4, and 99.7%, respectively. A total of 302 clinical isolates and
      reference strains were PVL positive and were assigned to 21 different clonal
      complexes. In summary, the lateral flow test allows rapid and economical
      detection of PVL in a routine bacteriology laboratory. As the test utilizes
      cultures from standard media and does not require sophisticated equipment, it can
      be easily integrated into a laboratory's workflow and might contribute to timely
      therapy of PVL-associated infections.

PMID- 23175261
TI  - Development and evaluation of a novel, semiautomated Clostridium difficile typing
      platform.
AB  - We describe a novel, semiautomated Clostridium difficile typing platform that is
      based on PCR-ribotyping in conjunction with a semiautomated molecular typing
      system. The platform is reproducible with minimal intra- or interassay
      variability. This method exhibited a discriminatory index of 0.954 and is
      therefore comparable to more arduous typing systems, such as pulsed-field gel
      electrophoresis.

PMID- 23175262
TI  - Rapid detection of Campylobacter antigen by enzyme immunoassay leads to increased
      positivity rates.
AB  - Campylobacter antigen detection by enzyme immunoassay (EIA) provides rapid
      results compared to traditional culture. However, concern exists regarding
      specificity. Verification studies of an EIA compared to culture revealed a
      positive predictive value (PPV) of 91%, whereas PPV fell to 42% during routine
      diagnostic testing. We suggest all positive EIA results be confirmed via culture.

PMID- 23175263
TI  - Evaluation of a new chromogenic agar medium for detection of Shiga toxin
      producing Escherichia coli (STEC) and relative prevalences of O157 and non-O157
      STEC in Manitoba, Canada.
AB  - This study assesses the detection performance of CHROMagar STEC medium relative
      to a reference cytotoxin assay and describes the current relative prevalence of
      O157 and non-O157 Shiga toxin-producing Escherichia coli (STEC) serotypes within
      the province of Manitoba, Canada. Over a 10-month period, 205 nonfrozen routine
      stool submissions to Cadham Provincial Laboratory (CPL) were used to assess the
      performance of CHROMagar STEC. Of the 205 stools, 14 were identified as true
      positives by a cytotoxin assay, with resultant CHROMagar STEC sensitivity,
      specificity, and positive predictive and negative predictive values of 85.7%,
      95.8%, 60.0%, and 98.9%, respectively. Using a separate panel of 111 STEC
      strains, CHROMagar STEC was shown to support the growth of 96 (86.5%) isolates.
      To assess relative prevalence, attempts were made to isolate by any means all
      STEC strains identified at CPL over a 17-month period. Of 49 isolates
      (representing 86.0% of all STEC infections detected), only 28.6% were O157 STEC
      strains. Of the 35 non-O157 STEC strains, 29 were subjected to further molecular
      analysis. In contrast to earlier results from our area, carriage of stx(2)
      appears to have increased. Overall, although CHROMagar STEC is not recommended as
      a primary screen, our results indicate that it is an effective supplemental
      medium for the isolation of probable STEC strains. Increased isolation of these
      serotypes is warranted to better understand their prevalence, clinical
      characteristics, and epidemiology and aid in the development or enhancement of
      food safety control programs targeting all STEC serotypes.

PMID- 23175264
TI  - Comparison of three different methods for detection of Shiga toxin-producing
      Escherichia coli in a tertiary pediatric care center.
AB  - Shiga toxin-producing Escherichia coli (STEC) is a well-known cause of sporadic
      and epidemic food-borne gastroenteritis. A low infectious dose, approximately 10
      microorganisms, is sufficient to cause disease that may lead to hemolytic-uremic
      syndrome. The objective of this study was to compare the performances of an in
      house real-time PCR, a commercial enzyme immunoassay (EIA) (Premier EHEC;
      Meridian Bioscience), and culture on sorbitol MacConkey agar for the detection of
      STEC in a tertiary care pediatric hospital. Of 632 stool samples tested, 21 were
      positive for STEC. All were detected by PCR, 6 were detected by EIA, and only 5
      O157 STEC isolates were identified by culture. Among the 15 specimens falsely
      negative by EIA, there were 9 Stx1, 2 Stx2, and 4 Stx1 and Stx2 STEC isolates.
      The latter group included 2 O157 STEC isolates that would have been missed if
      only EIA had been performed. To our knowledge, this is the first prospective
      study performed in a pediatric hospital which demonstrates the superiority of PCR
      over EIA for the detection of STEC. We conclude that PCR is specific and more
      sensitive than EIA. PCR should be considered for routine use in clinical settings
      where molecular detection facilities are available. Its lower limit of detection,
      equivalent to the infectious dose, is an obvious advantage for patient care and
      public health surveillance.

PMID- 23175265
TI  - Fatal alveolar echinococcosis of the lumbar spine.
AB  - For the last 10 years, the southern part of Belgium has been recognized as a low
      risk area of endemicity for alveolar echinococcosis. This infection, caused by
      Echinococcus multilocularis, usually induces a severe liver condition and can
      sometimes spread to other organs. However, alveolar echinococcosis involving
      bones has been described only very rarely. Here, a fatal case of spondylodiscitis
      due to E. multilocularis contracted in southern Belgium is reported.

PMID- 23175266
TI  - Detection of heterogeneity of Borrelia burgdorferi in ixodes ticks by culture
      dependent and culture-independent methods.
AB  - Abilities to detect heterogeneity of ospC genotypes of the Lyme disease
      spirochete Borrelia burgdorferi in the tick vector by in vitro culture (IVC) and
      direct PCR (dPCR) were compared. IVC failed to detect one-third of the ospC
      genotypes detected by dPCR. Among IVC results, common ospC genotypes were
      overrepresented while occurrence of rare genotypes was underestimated.

PMID- 23175267
TI  - Severe hepatitis associated with an echovirus 18 infection in an immune
      compromised adult.
AB  - Enteroviruses are recognized as important pathogens in pediatric patients;
      however, they are often overlooked as etiologic agents of disease in adults.
      Here, we report a case of echovirus 18-associated severe systemic infection and
      acute liver failure in an adult hematopoietic stem cell transplant recipient.
      Additionally, we illustrate the utility of molecular methods for the detection
      and typing of enteroviral infections.

PMID- 23175268
TI  - Gamma interferon release assay for monitoring of treatment response for active
      tuberculosis: an explosion in the spaghetti factory.
AB  - Few studies have correlated the results of interferon (gamma interferon) release
      assays (IGRAs) with known markers of tuberculosis (TB) treatment response. We
      report the results of serial QuantiFERON-TB gold in-tube assay (QFT) testing on
      149 patients with active tuberculosis and correlate the results with smear and
      culture conversion. We show that QFT results do not offer much value for
      treatment monitoring of TB disease.

PMID- 23175270
TI  - A randomized trial comparing conventional cytology to liquid-based cytology and
      computer assistance.
AB  - Liquid-based cytology (LBC) has replaced conventional cytology (CC) for cervical
      cancer screening in some countries. However, it remains unclear whether LBC is
      superior to CC. A randomized controlled trial was conducted between August 2007
      and March 2009 in Germany to compare LBC, alone and in combination with computer
      assisted imaging technology (CAS), to CC in the detection of histologically
      confirmed cervical intraepithelial neoplasia (CIN). The main outcome measures
      were detection rates, relative sensitivities, positive predictive values (PPVs)
      and relative PPVs comparing LBC without and with CAS to CC. Primary histological
      outcome was CIN2 or higher. Included were 20,627 women participating in
      opportunistic cervical cancer screening at 20 gynecologic practices. The
      practices were randomized weekly to use LBC (n = 11,331) or CC (n = 9,296).
      Patients with positive findings were invited to expert colposcopy. The relative
      sensitivity of LBC versus CC using the CIN2+ cut-off was 2.74 (95% confidence
      interval [CI] 1.66-4.53). The relative sensitivity of LBC/CAS versus CC for CIN2+
      was 3.17 (95% CI 1.94-5.19). The PPV of LBC and CC for CIN2+ was 48% and 38%,
      respectively. The PPV ratio did not differ significantly from unity. Differences
      between LBC and CC were smaller in some sensitivity and subgroup analyses;
      however, relative sensitivity of LBC remained increased. LBC without and with CAS
      compared with CC under the field conditions of an opportunistic screening system
      had a significantly higher sensitivity for the detection of CIN without
      deterioration of PPVs. Additional use of CAS did not further improve sensitivity
      of LBC. (c) 2012 Wiley Periodicals, Inc.

PMID- 23175269
TI  - A laboratory-developed TaqMan Array Card for simultaneous detection of 19
      enteropathogens.
AB  - The TaqMan Array Card (TAC) system is a 384-well singleplex real-time PCR format
      that has been used to detect multiple infection targets. Here we developed an
      enteric TaqMan Array Card to detect 19 enteropathogens, including viruses
      (adenovirus, astrovirus, norovirus GII, rotavirus, and sapovirus), bacteria
      (Campylobacter jejuni/C. coli, Clostridium difficile, Salmonella, Vibrio
      cholerae, diarrheagenic Escherichia coli strains including enteroaggregative E.
      coli [EAEC], enterotoxigenic E. coli [ETEC], enteropathogenic E. coli [EPEC], and
      Shiga-toxigenic E. coli [STEC]), Shigella/enteroinvasive E. coli (EIEC), protozoa
      (Cryptosporidium, Giardia lamblia, and Entamoeba histolytica), and helminths
      (Ascaris lumbricoides and Trichuris trichiura), as well as two extrinsic controls
      to monitor extraction and amplification efficiency (the bacteriophage MS2 and
      phocine herpesvirus). Primers and probes were newly designed or adapted from
      published sources and spotted onto microfluidic cards. Fecal samples were spiked
      with extrinsic controls, and DNA and RNA were extracted using the QiaAmp Stool
      DNA minikit and the QuickGene RNA Tissue kit, respectively, and then mixed with
      Ag-Path-ID One Step real-time reverse transcription-PCR (RT-PCR) reagents and
      loaded into cards. PCR efficiencies were between 90% and 105%, with linearities
      of 0.988 to 1. The limit of detection of the assays in the TAC was within a 10
      fold difference from the cognate assays performed on plates. Precision testing
      demonstrated a coefficient of variation of below 5% within a run and 14% between
      runs. Accuracy was evaluated for 109 selected clinical specimens and revealed an
      average sensitivity and specificity of 85% and 77%, respectively, compared with
      conventional methods (including microscopy, culture, and immunoassay) and 98% and
      96%, respectively, compared with our laboratory-developed PCR-Luminex assays.
      This TAC allows fast, accurate, and quantitative detection of a broad spectrum of
      enteropathogens and is well suited for surveillance or clinical purposes.

PMID- 23175271
TI  - Flow-injection chemiluminescence determination of diazepam by oxidation with N
      bromosuccinimide.
AB  - A rapid and sensitive flow-injection chemiluminescence (FI-CL) method is
      described for the determination of diazepam based on its reaction with N
      bromosuccinimide (NBS) in alkaline medium in the presence of dichlorofluorescein
      (DCF) as an effective energy-transfer agent. Under optimum conditions, the
      proposed method allowed the measurement of diazepam over the range of 2.0 * 10(
      6) to 2.0 * 10(-4) mol/L with a detection limit of 5.0 * 10(-7) mol/L. The
      relative standard deviation for 11 parallel measurements of 2.0 * 10(-5) mol/L
      diazepam was 2.1%. The method was applied satisfactorily for the determination of
      diazepam in pharmaceutical preparations, and the results agree well with those
      obtained by spectrophotometry. The use of the proposed system for the
      determination of diazepam in urine and plasma samples was also tested. The
      possible mechanism of the chemiluminescence reaction is discussed briefly.

PMID- 23175272
TI  - Molecular cloning, characterization and differential expression of DRK1 in
      Sporothrix schenckii.
AB  - The dimorphism of Sporothrix schenckii (S. schenckii) reflects a developmental
      switch in morphology and lifestyle that is necessary for virulence. DRK1, a
      hybrid histidine kinase, functions as a global regulator of dimorphism and
      virulence in Blastomyces dermatitidis (B. dermatitidis) and Histoplasma
      capsulatum (H. capsulatum). The partial cDNA sequence of DRK1 of S. schenckii,
      designated SsDRK1, was obtained using degenerate primers based on the conserved
      domain of the DRK1 of other fungi. The complete cDNA sequence of SsDRK1 was
      obtained by 5' and 3' RACE. The full-length cDNA is 4743 bp in size and has an
      open reading frame (ORF) of 4071 bp, encoding 1356 amino acid residues. The
      predicted molecular mass of SsDRK1 is 147.3 kDa with an estimated theoretical
      isoelectric point of 5.46. The deduced amino acid sequence of SsDRK1 shows 65%
      identity to that of B. dermatitidis. The SsDRK1 was predicted to be a soluble
      histidine kinase and to contain three parts: sensor domain, linker domain and
      functional domain. Quantitative real-time RT-PCR revealed that SsDRK1 was more
      highly expressed in the yeast stage compared with that in the mycelial stage,
      which indicated that the SsDRK1 may be involved in the dimorphic switch in S.
      schenckii.

PMID- 23175273
TI  - Oxidative stress plays a major role in chlorpromazine-induced cholestasis in
      human HepaRG cells.
AB  - Drugs induce cholestasis by diverse and still poorly understood mechanisms in
      humans. Early hepatic effects of chlorpromazine (CPZ), a neuroleptic drug known
      for years to induce intrahepatic cholestasis, were investigated using the
      differentiated human hepatoma HepaRG cells. Generation of reactive oxygen species
      (ROS) was detected as early as 15 minutes after CPZ treatment and was associated
      with an altered mitochondrial membrane potential and disruption of the
      pericanalicular distribution of F-actin. Inhibition of [3H]-taurocholic acid
      efflux was observed after 30 minutes and was mostly prevented by N-acetyl
      cysteine (NAC) cotreatment, indicating a major role of oxidative stress in CPZ
      induced bile acid (BA) accumulation. Moreover, 24-hour treatment with CPZ
      decreased messenger RNA (mRNA) expression of the two main canalicular bile
      transporters, bile salt export pump (BSEP) and multidrug resistance protein 3
      (MDR3). Additional CPZ effects included inhibition of Na+ -dependent taurocholic
      cotransporting polypeptide (NTCP) expression and activity, multidrug resistance
      associated protein 4 (MRP4) overexpression and CYP8B1 inhibition that are
      involved in BA uptake, basolateral transport, and BA synthesis, respectively.
      These latter events likely represent hepatoprotective responses which aim to
      reduce intrahepatic accumulation of toxic BA. Compared to CPZ effects,
      overloading of HepaRG cells with high concentrations of cholic and
      chenodeoxycholic acids induced a delayed oxidative stress and, similarly, after
      24 hours it down-regulated BSEP and MDR3 in parallel to a decrease of NTCP and
      CYP8B1 and an increase of MRP4. By contrast, low BA concentrations up-regulated
      BSEP and MDR3 in the absence of oxidative stress. CONCLUSION: These data provide
      evidence that, among other mechanisms, oxidative stress plays a major role as
      both a primary causal and an aggravating factor in the early CPZ-induced
      intrahepatic cholestasis in human hepatocytes.

PMID- 23175274
TI  - [Ultrasound versus MRI in preventive examinations - a retrospective analysis of
      833 patients].
AB  - PURPOSE: The benefit of ultrasound in comparison with full-body MRI during a
      medical checkup in preventive health care was examined with regard to the
      detection of cardiovascular risk factors, metabolic syndrome, malignant tumors
      and further relevant findings. MATERIALS AND METHODS: 833 consecutive patients
      (266 f/567 m, age: 19 - 93 y, mean age: 56.6 y) underwent both ultrasound
      (extracranial carotid arteries, thyroid, abdominal ultrasound and
      echocardiography) and whole-body MRI (whole-body MR angiography, head, thorax,
      abdomen and virtual colonoscopy). For ultrasound examinations, DEGUM level III
      devices were used (Siemens Acuson Antares, Siemens G60, Siemens, Erlangen). MRI
      examinations were performed using a 1.5 Tesla MRI device (Siemens Avanto,
      Siemens, Erlangen). All patients were reviewed retrospectively based on the
      written reports. RESULTS: Ultrasound was much more sensitive in detecting early
      atherosclerotic changes than MRI angiography. In 33 % of the patients,
      manifestations of atherosclerosis were found. Thoracic (3) and abdominal aortic
      and mesenteric artery aneurysms (3) were diagnosed by both methods. Hepatic
      steatosis as an important risk factor of metabolic syndrome was only found by
      ultrasound in 20.4 % of our patients. Malignant tumors were rare in this
      population (1.4 %): all abdominal tumors except one renal oncocytoma were found
      using both methods. MRI and ultrasound were equally sensitive with respect to the
      detection of small liver foci. As expected, MRI was less sensitive than
      ultrasound in the diagnosis of thyroid nodes. For intracranial diagnoses,
      malignant intrathoracic findings and colonic polyps, ultrasound is not the method
      of choice. CONCLUSION: For the detection of lifestyle-dependent diseases such as
      atherosclerosis and metabolic syndrome, ultrasound examination was more sensitive
      than MRI, and the same was true for the early detection of thyroid diseases. For
      the detection of malignant abdominal tumors, both methods were equally sensitive.
      Whole-body MRI can additionally detect pathological changes in the head, lungs
      and colon.

PMID- 23175275
TI  - Chromatin: a matter of inheritance.

PMID- 23175278
TI  - Organelle dynamics: a histone anchor on lipid droplets.

PMID- 23175279
TI  - Cell migration: the mechanics of group travel.

PMID- 23175280
TI  - Function and regulation of SUMO proteases.
AB  - Covalent attachment of small ubiquitin-like modifier (SUMO) to proteins is highly
      dynamic, and both SUMO-protein conjugation and cleavage can be regulated. Protein
      desumoylation is carried out by SUMO proteases, which control cellular mechanisms
      ranging from transcription and cell division to ribosome biogenesis. Recent
      advances include the discovery of two novel classes of SUMO proteases, insights
      regarding SUMO protease specificity, and revelations of previously unappreciated
      SUMO protease functions in several key cellular pathways. These developments,
      together with new connections between SUMO proteases and the recently discovered
      SUMO-targeted ubiquitin ligases (STUbLs), make this an exciting period to study
      these enzymes.

PMID- 23175281
TI  - Mitochondria: master regulators of danger signalling.
AB  - Throughout more than 1.5 billion years of obligate endosymbiotic co-evolution,
      mitochondria have developed not only the capacity to control distinct molecular
      cascades leading to cell death but also the ability to sense (and react to)
      multiple situations of cellular stress, including viral infection. In addition,
      mitochondria can emit danger signals that alert the cell or the whole organism of
      perturbations in homeostasis, hence promoting the induction of cell-intrinsic or
      systemic adaptive responses, respectively. As such, mitochondria can be
      considered as master regulators of danger signalling.

PMID- 23175283
TI  - Neuroanatomy of the female abdominopelvic region: A review with application to
      pelvic pain syndromes.
AB  - Pelvic pain can be a life altering disease. Multiple pathologies can affect this
      region resulting in neurologic issues. Therefore, a thorough understanding of the
      nerve supply to this region is important for the clinician who treats such
      patients. The current review outlines the anatomy of the nervous system of the
      abdominopelvic region with special attention to this anatomy in the female.

PMID- 23175284
TI  - Active conversion to the prion state as a molecular switch for cellular
      adaptation to environmental stress.

PMID- 23175285
TI  - The gallbladder of the electric ray Torpedo marmorata Risso displays excrescent
      cholecystocytes with merocrine and apocrine-like secretions.
AB  - The gallbladder of Torpedo marmorata exhibits a mucosal surface layer of simple
      columnar epithelium with very tall cholecystocytes. The apical domain of each
      cell has few microvilli, but many mucous vesicles that are secreted by exocytosis
      at the cell apices. The apical regions may also elongate and undergo self
      excision while shedding mucus and cell debris into the gallbladder lumen in a
      manner similar to that described in mammals as a result of sex steroid treatment
      to induce gallstones and to that found in the cholecystitis associated with
      cholelithiasis. Numerous small mitochondria, spherical to elongated, are
      distributed throughout the cells, while the nuclei are often located in the lower
      third of each cell. In the lower part of the cholecystocytes, large and very
      densely contrasted lysosomes can be found. All cells are tightly joined by
      junctional complexes, including long, highly contrasted desmosomes. The
      fibromuscular layer is made of a loose stroma with a limited muscular component
      and a poor blood supply. Large diameter blood vessels can only be found in the
      subserosal layer. It is hypothesized that the obligatorily carnivorous diet of
      this ureotelic fish has resulted in the evolution of a gallbladder ultrastructure
      resembling that found in cholecystitis but without the associated cholelithiasis.

PMID- 23175286
TI  - Integration of patient-reported outcome measures with key clinical outcomes after
      immediate latissimus dorsi breast reconstruction and adjuvant treatment.
AB  - BACKGROUND: Clinical evidence on patient-reported outcome measures (PROMS) in
      breast reconstruction is lacking. The aim of this study was to evaluate PROMs in
      implant-assisted latissimus dorsi (LDI) or tissue-only autologous latissimus
      dorsi (ALD) flap reconstruction in relation to complications and adjuvant
      treatments. METHODS: This was a prospective cohort study involving six UK
      centres. Eligible patients had primary early-stage breast cancer. The European
      Organization for Research and Treatment of Cancer quality-of-life questionnaire
      (QLQ)-C30 and QLQ-BR23, Functional Assessment of Cancer Therapy-Breast Cancer
      scale (FACT-B), Body Image Scale, and Hospital Anxiety and Depression Scale were
      completed before operation and at 3, 6 and 12 months after surgery. RESULTS: A
      total of 182 patients (82 LDI and 100 ALD) were recruited between 2007 and 2010
      with symptomatic (59.9 per cent) or screen-detected (39.6 per cent) cancers. Some
      64.3 per cent had lymph node-negative disease; 30 per cent of the LDI group had
      radiotherapy, compared with 53.0 per cent in the ALD group (P = 0.004). Early
      complications up to 3 months after surgery were reported in 66 and 51.0 per cent
      of patients in the LDI and ALD groups respectively (P = 0.062) and long-term
      complications (4-12 months) in 48 and 45.0 per cent (P = 0.845). Role functioning
      and pain (P = 0.002 for both) were adversely affected in the ALD group compared
      with results in the LDI group, with no significant effects of radiotherapy on any
      health-related quality of life (HRQL). Chemotherapy and early complications
      adversely affected HRQL, which improved between 3 and 12 months after surgery (P
      < 0.010 for all). CONCLUSION: There is evidence of similar HRQL between types of
      latissimus dorsi breast reconstruction for up to a year after surgery. There
      appear to be no overarching effects for radiotherapy after mastectomy on the
      specific HRQL domains studied in the short term. The identification of variables
      that affect HRQL is important, including their integration into the analysis of
      PROMs.

PMID- 23175282
TI  - The chromosomal passenger complex (CPC): from easy rider to the godfather of
      mitosis.
AB  - Successful cell division requires the precise and timely coordination of
      chromosomal, cytoskeletal and membrane trafficking events. These processes are
      regulated by the competing actions of protein kinases and phosphatases. Aurora B
      is one of the most intensively studied kinases. In conjunction with inner
      centromere protein (INCENP), borealin (also known as Dasra) and survivin it forms
      the chromosomal passenger complex (CPC). This complex targets to different
      locations at differing times during mitosis, where it regulates key mitotic
      events: correction of chromosome-microtubule attachment errors; activation of the
      spindle assembly checkpoint; and construction and regulation of the contractile
      apparatus that drives cytokinesis. Our growing understanding of the CPC has seen
      it develop from a mere passenger riding on the chromosomes to one of the main
      controllers of mitosis.

PMID- 23175287
TI  - Performance characteristics of current-generation Immulite 2000 TORCH Assays.
AB  - The performances of seven Immulite 2000 (Siemens Healthcare Diagnostics) TORCH
      (Toxoplasma gondii, other microorganisms, rubella virus, cytomegalovirus, and
      herpes simplex virus) assays were evaluated in comparison with the performances
      of the ETI-MAX 3000 (DiaSorin) TORCH assays. The two systems demonstrated good
      agreement, and given their sensitivity, specificity, and positive predictive
      value, they can be used with confidence for TORCH prenatal screening.

PMID- 23175288
TI  - Absolute lymphocyte count predicts the response to new influenza virus H1N1
      vaccination in pediatric cancer patients.
AB  - We measured the vaccination response to the new H1N1 virus in relation to the
      lymphocyte count prior to vaccination in pediatric cancer patients. The absolute
      lymphocyte count above the lower normal limits (LNL) for age prior to vaccination
      predicts the response to influenza vaccination in pediatric cancer patients
      treated with chemotherapy.

PMID- 23175291
TI  - Quantum transport through an array of quantum dots.
AB  - The transient current through an array of as many as 1000 quantum dots is
      simulated with two newly developed quantum mechanical methods. To our surprise,
      upon switching on the bias voltage, the current increases linearly with time
      before reaching its steady state value. And the time required for the current to
      reach its steady state value is proportional to the length of the array, and more
      interestingly, is exactly the time for a conducting electron to travel through
      the array at the Fermi velocity. These quantum phenomena can be understood by a
      simple analysis on the energetics of an equivalent classical circuit. An
      experimental design is proposed to confirm the numerical findings.

PMID- 23175289
TI  - On the efficacy and safety of vaccination with live tachyzoites of Neospora
      caninum for prevention of neospora-associated fetal loss in cattle.
AB  - Infection of cattle with Neospora caninum may result in abortion or the birth of
      a congenitally infected calf. Vaccination with live N. caninum protects against
      experimental infection of cattle and mice, and the naturally attenuated Nc-Nowra
      strain of N. caninum is of particular interest as a potential vaccine candidate.
      Vaccination of heifers prior to breeding with live Nc-Nowra tachyzoites by either
      the subcutaneous or the intravenous route reduced the rate of abortion and the
      presence of the parasite in calves as determined by PCR and serology after
      infection of cows with a virulent isolate. Protected fractions were 55.6% to
      85.2% depending on the route of vaccination and growth conditions of the vaccine
      strain, with cryopreserved Nc-Nowra tachyzoites being less effective, with a
      25.9% protected fraction. Vaccination appeared to reduce the rate of pregnancy
      after artificial insemination in some groups compared to nonvaccinated,
      nonchallenged controls. One animal that was vaccinated but not challenged
      experienced an abortion, but Nc-Nowra could not be detected in any of the cows in
      this group or their progeny. This study confirms that live vaccination can be an
      effective method of preventing neosporosis in cattle and yet highlights the
      technical hurdle of preservation of live parasites that must be overcome for a
      vaccine to be commercially successful.

PMID- 23175290
TI  - Incidence rates of clinical mastitis among Canadian Holsteins classified as high,
      average, or low immune responders.
AB  - The objective of this study was to compare the incidence rate of clinical
      mastitis (IRCM) between cows classified as high, average, or low for antibody
      mediated immune responses (AMIR) and cell-mediated immune responses (CMIR). In
      collaboration with the Canadian Bovine Mastitis Research Network, 458 lactating
      Holsteins from 41 herds were immunized with a type 1 and a type 2 test antigen to
      stimulate adaptive immune responses. A delayed-type hypersensitivity test to the
      type 1 test antigen was used as an indicator of CMIR, and serum antibody of the
      IgG1 isotype to the type 2 test antigen was used for AMIR determination. By using
      estimated breeding values for these traits, cows were classified as high,
      average, or low responders. The IRCM was calculated as the number of cases of
      mastitis experienced over the total time at risk throughout the 2-year study
      period. High-AMIR cows had an IRCM of 17.1 cases per 100 cow-years, which was
      significantly lower than average and low responders, with 27.9 and 30.7 cases per
      100 cow-years, respectively. Low-AMIR cows tended to have the most severe
      mastitis. No differences in the IRCM were noted when cows were classified based
      on CMIR, likely due to the extracellular nature of mastitis-causing pathogens.
      The results of this study demonstrate the desirability of breeding dairy cattle
      for enhanced immune responses to decrease the incidence and severity of mastitis
      in the Canadian dairy industry.

PMID- 23175292
TI  - [Access to health services: approaches, concepts, policies and analysis model].
AB  - Access to health services is a multifaceted and multidimensional issue involving
      political, economic, social, organizational, technical and symbolic aspects in
      establishing access to universal healthcare. This theoretical review paper
      intends to discuss the different approaches, analyze the context and policies for
      special groups on access, marking an analysis model delineated by the above
      aspects, from readings on the topic in question. This analysis reveals a
      diversity of approaches to access the formulation and implementation of public
      policies and their potential for changing the organization of the health system.
      We identified progress in reducing inequalities in health and increased access to
      the network of the Unified Health System (SUS), especially in primary care. There
      were also limitations related to accessibility, fragmentation, decentralization
      and regionalization of the service network, with inadequacies in the process of
      care and attention to specific groups, and regional disparities. Finally, the
      analysis model proposed seeks to develop a critical stance to reflect and
      intervene in health practices and services, with the objective goal being
      responsible, comprehensive, effective, equitable and quality healthcare.

PMID- 23175293
TI  - [Access to health actions and services: a polysemic approach].

PMID- 23175294
TI  - [Inputs and banners and the Unified Health System (SUS) in the twenty-first
      century].

PMID- 23175295
TI  - [Regionalization and access to healthcare in Brazilian states: historical and
      political-institutional conditioning factors].
AB  - This article examines the healthcare regionalization process in the Brazilian
      states in the period from 2007 to 2010, seeking to identify the conditions that
      favor or impede this process. Referential analysis of public policies and
      especially of historical institutionalism was used. Three dimensions sum up the
      conditioning factors of regionalization: context (historical-structural,
      political-institutional and conjunctural), directionality (ideology, object,
      actors, strategies and instruments) and regionalization features
      (institutionality and governance). The empirical research relied mainly on the
      analysis of official documents and interviews with key actors in 24 states.
      Distinct patterns of influence in the states were observed, with regionalization
      being marked by important gains in institutionality and governance in the period.
      Nevertheless, inherent difficulties of the contexts prejudice greater advances.
      There is a pressing need to broaden the territorial focus in government planning
      and to integrate sectorial policies for medium and long-term regional development
      in order to empower regionalization and to overcome obstacles to the access to
      healthcare services in Brazil.

PMID- 23175296
TI  - [Primary healthcare and the construction of thematic health networks: what role
      can they play?].
AB  - The enhancement of primary healthcare has been a core strategy for the
      empowerment of the Brazilian Unified Health System (SUS). Recent guidelines
      issued by OPAS and the Ministry of Health highlight the role it has played as a
      thematic communication network center, a regulating agent for the access and use
      of services required for comprehensive healthcare. Sponsored by PPSUS/Fapesp,
      this study examines the possibilities of the primary healthcare network
      exercising such a strategic function. Life narratives involving 15 regular users
      were produced in two cities of ABC Paulista, which have adopted the Family Health
      Strategy for the organization of their primary healthcare networks. The study
      presents three main findings: the primary healthcare network serves as an outpost
      of SUS by producing user values even for high complexity service users; the
      primary network is perceived is a place for simple care needs; there is shared
      impotence between users and teams when it comes to the network functioning as the
      coordinator of care, indicating that it does not possess the technological,
      operational and organizational material conditions or symbolic conditions
      (values, meanings, and representations) to be in a central position in the
      coordination of thematic healthcare networks.

PMID- 23175297
TI  - [Access to primary healthcare services: still a way to go].
AB  - This study seeks to evaluate accessibility to the Basic Units of the Family
      Health Strategy (ESF-UB) and Traditional Basic Units (BU-T) in the city of Recife
      in 2009. Data were collected through three instruments: a roadmap for systematic
      observation of the units and questionnaires for users and professional units.
      This is a descriptive cross-sectional study using a quantitative approach, and
      1180 users, 61 doctors and 56 nurses were interviewed. The results showed good
      ties and recognition of users whereby primary healthcare is seen as the access
      portal to the health system. In the comparison between ESF-UB and UB-T,
      evaluations are always more favorable to the family healthcare strategy, though
      with relatively insignificant differences. The overall result revealed widespread
      dissatisfaction with the difficulty of obtaining drugs and taking tests, and also
      with the waiting times and access to specialized care. This showed the existence
      of organizational problems that may constitute barriers limiting accessibility to
      basic healthcare services for users.

PMID- 23175299
TI  - [Access, educational practice and empowerment of patients with chronic diseases].
AB  - Empowerment is a process whereby people achieve mastery over their lives,
      acquiring knowledge to make decisions about their health. Chronic diseases are
      increasingly common in the health service, requiring the attention of health
      professionals and empowering those affected by them. The scope of this study was
      to analyze the perceptions of users with chronic diseases and monitored by the
      Family Health Program with respect to empowerment. This was a qualitative study
      in which open interviews and systematic observations were conducted and NVIVO
      software was used for data analysis. Users indicate the existence of some
      geographical barriers in access to health, which caused fatigue, discouragement
      and low continuity of care. It was noted that adherence and practices of care
      were linked to differentiated service, based on trust and respect for the wishes
      of users. This includes healthcare guidance and education as key elements to
      encourage the practice of self-care. It is necessary to restructure the conduct
      of health professionals involved in the Family Health Strategy because its
      function is to promote health in a logical intersectoral and interdisciplinary
      manner.

PMID- 23175298
TI  - [Access to the Family Healthcare Program in an area with "extensive" coverage of
      the private healthcare system].
AB  - The access profile to the various services offered by the Family Health Program
      (PSF) in an area with extensive private health system coverage is studied in the
      city of Santo Andre, state of Sao Paulo. The sample was studied in two phases
      based on the assumption that the use of the activities offered by the Family
      Health Program is not uniform. Residual, full and partial population groups were
      therefore considered. Interviews were conducted with 175 individuals and the
      registered population is composed of full (0.5%), partial (31.0%) and residual
      (68.5%) users. In the bivariate analysis, significant differences were observed
      between partial and residual groups in relation to age, income, employment,
      affiliation to the private subsystem and years of schooling. However, the ratios
      of prevalence when estimated by the Poisson multiple model indicate that the
      factors that influence the access profile of the PSF activities are private
      subsystem membership and income. This highlights the fact that some services
      offered do not reach more than 20% of the population. Despite the immense
      potential of innovative proposals incorporated by the PSF, this study shows that
      there is selective use of its activities by the population, strongly influenced
      by private subsystem affiliation and income.

PMID- 23175300
TI  - [Community health workers: promoters of interaction between territories].
AB  - This article presents reflections originating from a series of meetings with
      community health workers over a period of ten years. It identifies the
      consolidation of two existential territories, which are sometimes closer and at
      other times more distant from each other, namely the territory of technical
      knowledge about health and the territory of popular knowledge about health.
      Starting with the analysis of some quotes from health workers and reflections
      which tally with the theoretical reference in the area, this paper discusses some
      of the dilemmas and deadlocks of access and affiliation from the perspective of
      some of these health workers, as well as the strategies devised on a day-to-day
      basis from the crossovers that take place between these two territories. It
      identifies the function of community health workers as frontier agents, at times
      acting as inventors or motivators of contact zones between the territories, and
      at other times acting as a representative by one territory inside the other.

PMID- 23175301
TI  - [The viewpoint of health professionals on the role of basic units in the
      healthcare network of the Brazilian Unified Health System].
AB  - In the process of creation of the Unified Health System (SUS) as a universal
      policy seeking to ensure comprehensive care, unscheduled assistance in primary
      healthcare units (UBS) is an unresolved challenge. The scope of this paper is to
      analyze the viewpoint of health professionals on the role of primary healthcare
      units in meeting this demand. It is a transversal study of qualitative data
      obtained through questionnaires and interviews with 106 medical practitioners
      from 6 emergency medical services and 190 professionals from 30 units. They
      explained why people seek emergency care for occurrences pertaining to primary
      care. The content analysis technique with thematic categories was used for data
      analysis. Lack of resources and problems with primary health unit work processes
      (50.8%) were the reasons most frequently cited by emergency care physicians to
      explain this inadequate demand. Only 33.3% of the health unit professionals
      agreed that these occurrences should be attended in the primary healthcare
      services. The limited viewpoint of the role of health services on the unscheduled
      care, particularly among primary care professionals, possibly leads to
      restrictive practices for access by the population.

PMID- 23175302
TI  - [Inequalities in mortality from cardiovascular diseases in small municipalities].
AB  - The scope of this ecological study was to identify mortality from cardiovascular
      disease in the municipalities of the 16th Health Region of Rio Grande do Sul
      between 2003 and 2007. It looked at differences among them, sex and age
      distribution and related the mean coefficient of mortality during the period to
      socioeconomic variables of investment, healthcare coverage and access, seeking to
      identify a few factors that might be significant to explain these differences.
      Correlation and multiple regression were analyzed. The results indicated that in
      counties with up to 5000 inhabitants the Family Health Strategy coverage may be a
      better protective factor than in larger municipalities, and per capita income has
      less influence on mortality. A direct relationship was found between hospital
      admissions for cardiovascular disease and mortality, especially in the larger
      municipalities. Multiple regression showed health costs per inhabitant/year as
      the factor most closely related to increased mortality. It was concluded that the
      variables selected explain partially the differences in mortality caused by
      cardiovascular disease in a similar group of municipalities of a regional health
      area in southern Brazil.

PMID- 23175303
TI  - [Regional differences in access to coronary bypass surgery in Brazil, 2002-2010].
AB  - The hospitalization rates for angioplasty and coronary bypass surgery have been
      used as proxies for access to highly specialized services. The scope of this
      study is to analyze the evolution of these rates and discuss what are the
      possible causes associated with regional inequalities. Standardized rates of
      angioplasty and coronary bypass surgery by age and sex per 100,000 inhabitants
      aged 20 and over, in the period from 2002 to 2010 were calculated. Comparison
      with international data shows that Brazil has lower rates than those observed in
      OECD countries. In Brazil, the standardized rates of hospitalization for
      angioplasty in the population aged 20 and over showed an upward trend, rising
      from 27.5 per 100,000 in 2002 to 39 in 2010. When mortality rates by age and sex
      from different geographical regions were compared, besides the marked differences
      in the north - south axis, what is notable is the maintenance of a stable pattern
      of these rates and regional differences over the period analyzed. The definition
      of regional health care networks for cardiac surgery is an important strategy to
      ensure the quality of care, optimization of operating costs and reduction of
      inequalities in access to healthcare between Brazilian regions.

PMID- 23175304
TI  - [Study on blindness: mortality of patients with chronic kidney disease during non
      elective hemodialysis].
AB  - Chronic kidney disease (CKD) leads to renal failure and the need for renal
      replacement therapy (RRT). Secondary prevention may postpone CKD for many years.
      This retrospective study sought to analyze prognostic factors and estimate the
      mortality of patients with CKD secondary to diabetes mellitus and to hypertension
      that initiate RRT through non-elective hemodialysis at an emergency hospital unit
      in Rio de Janeiro, from hospital admission until transfer to referral units. The
      mortality rate was 35.1%. The study detected a significant difference between the
      survival curves according to disease etiology (log-rank and Peto, p=0.02) and the
      presence of functional arteriovenous fistulae (log-rank, p=0.0099; Peto,
      p=0.0090). Multivariate analysis (Cox model) revealed a 7% increase in the risk
      of death (p=0.002) by one-year increment in age; the presence of a functional
      fistule was associated to an 81% reduction in the risk of death (p=0.03). About
      one third of patients with CKD followed by hypertension or diabetes that initiate
      renal replacement therapy through non-elective hemodialysis die before being
      transferred to a referral unit, indicating low access to secondary prevention in
      CKD, including surgery for arteriovenous fistula creation.

PMID- 23175305
TI  - [Market and public policy network failures: challenges and possibilities for the
      Brazilian Unified Health System].
AB  - The principles and guidelines of the Brazilian Unified Health System (SUS) impose
      a healthcare service structure based on public policy networks which, combined
      with the financing model adopted, leads to market failings. This imposes barriers
      to the management of the public health system and the enactment of SUS
      objectives. The institutional characteristics and the heterogeneity of players,
      allied to the existence of different healthcare approaches, generate analytical
      complexity in the study of the global dynamics of the SUS network. There are
      limitations in the use of quantitative methods based on static analysis of
      retrospective SUS data. Thus, an approach taking SUS as a complex system using
      innovative quantitative methodology based on computational simulation is
      proposed. This paper sought to analyze challenges and possibilities of the
      combined application of cellular automata modeling and agent-based modeling for
      simulation of the evolution of the SUS healthcare service network. This approach
      should permit better understanding of the organization, heterogeneity and
      structural dynamics of the SUS service network and a minimization of the effects
      of market failings on the Brazilian health system.

PMID- 23175306
TI  - [Factors associated with difficulty of access of the elderly with disabilities to
      the health services].
AB  - This study seeks to analyze which are the variables associated with the
      difficulty of elderly people with disabilities gaining access to the health
      services. This is an observational study of an analytical cross-sectional nature,
      with a sample of 244 elderly people with disabilities. Data relating to socio
      economic profile, the nature of the disability, and the conditions of access to
      health services were gathered. Version 11.0 of the Statistical Package for the
      Social Sciences software was used for descriptive, statistical and analytical
      assessment of the data. The protection variables for difficulties in being
      treated in the health services were: the lack of drains, culverts, trash, bags of
      refuse, or irregular floor surfaces; the absence of ramps on sidewalks and
      pavements; the availability of transport; ease in scheduling appointments; and
      the length of the waiting period to be attended. The number of factors listed
      shows that the architectonic barriers and the current situation of healthcare
      need to be adequate in order to ensure full access and use by the elderly with
      disabilities to the health services.

PMID- 23175307
TI  - [Therapeutic itineraries of users of medication in a unit of the Family Heatlh
      Strategy].
AB  - Therapeutic itineraries represent the trajectories taken by individuals in an
      attempt to resolve their health problems. The objective of this study was to
      analyze the trajectory when user prescription medication needs were not met in a
      Family Health Strategy Unit of the city of Porto Alegre. A database of users
      whose prescription needs were not fully met and the application of a
      questionnaire during home visits was performed. Users interviewed were between 53
      and 85 years of age. The main problems reported were lack of money, physical
      difficulty in locomotion, side effects, illegible prescriptions, unavailability
      of medication in the local pharmacies of the city, fear of effects attributed to
      the medication, and "bureaucracy." When the medication is not available at the
      health unit, most users (60%) reported buying it. With respect to the
      communication of the family health team in the orientation of ways that the user
      can gain access to the medication, 25% of the respondents reported that the team
      did not provide necessary information about the alternate location for the
      acquisition of the medication that was lacking.

PMID- 23175308
TI  - [A method for the implementation and promotion of access to comprehensive and
      complementary primary healthcare practices].
AB  - The rendering of integrated and complementary practices in the Brazilian Unified
      Health System is fostered to increase the comprehensiveness of care and access to
      same, though it is a challenge to incorporate them into the services. Our
      objective is to provide a simple method of implementation of such practices in
      Primary Healthcare, derived from analysis of experiences in municipalities, using
      partial results of a master's thesis that employed research-action methodology.
      The method involves four stages: 1 - defininition of a nucleus responsible for
      implementation and consolidation thereof; 2 - situational analysis, with
      definition of the existing competent professionals; 3 - regulation, organization
      of access and legitimation; and 4 - implementation cycle: local plans, mentoring
      and ongoing education in health. The phases are described, justified and briefly
      discussed. The method encourages the development of rational and sustainable
      actions, sponsors participatory management, the creation of comprehensivenessand
      the broadening of care provided in Primary Healthcare by offering progressive and
      sustainable comprehensive and complementary practices.

PMID- 23175309
TI  - [Analysis of demand for family medical care in Brazil using the International
      Classification of Primary Care].
AB  - In various countries, motives for contact of patients with Primary Health Care
      (PHC) is classified by the International Classification of Primary Care (ICPC-2).
      This instrument enables the assessment of why people seek care, thereby assisting
      in planning strategies to attend the population's health needs. The scope of this
      study was to identify the main reasons for same-day appointments in PHC units of
      a medium-sized Brazilian city. The methodology used was to examine all records of
      a typical month of three family practice residents. Data were extracted from a
      secondary database of same-day appointments during the spring of 2010, classified
      with ICPC and then statistically analyzed. 1222 records were considered; 32
      motives accounted for 50% of contacts. Most common motives were related to the
      General and Unspecific chapter of the ICPC. About 20% of visits occurred for
      administrative reasons. Female sex and greater age were determinants of greater
      motives for consultation. Knowing the motives for appointments by gender and age
      may help PHC teams in tackling health problems at the critical point of access to
      PHC.

PMID- 23175310
TI  - [Rationale and knowledge for the universal implementation of sanitation in areas
      of social vulnerability].
AB  - The adoption of principles of equality and universality stipulated in legislation
      for the sanitation sector requires discussions on innovation. The existing model
      was able to meet sanitary demands, but was unable to attend all areas causing
      disparities in vulnerable areas. The universal implementation of sanitation
      requires identification of the know-how that promotes it and analysis of the
      model adopted today to establish a new method. Analysis of how different
      viewpoints on the restructuring process is necessary for the definition of public
      policy, especially in health, and understanding its complexities and importance
      in confirming social practices and organizational designs. These are discussed to
      contribute to universal implementation of sanitation in urban areas by means of a
      review of the literature and practices in the industry. By way of conclusion, it
      is considered that accepting a particular concept or idea in sanitation means
      choosing some effective interventions in the network and on the lives of
      individual users, and implies a redefinition of the space in which it exercises
      control and management of sewerage networks, such that connected users are
      perceived as groups with different interests.

PMID- 23175311
TI  - [Access to primary health care in a sanitary district of Salvador].
AB  - The demand for and use of health services results from a set of determinants that
      include socioeconomic, demographic and health characteristics and organization of
      the supply of services. The scope of this paper is to define access to and use of
      the health services in two Family Health Units (FHUs) of the sanitary district of
      Liberdade, establishing the pattern of use and identifying factors related to
      socio-organizational and geographical access. A cross-sectional population-based
      survey was conducted on individuals aged between 20 and 75 resident in the area
      covered by the two FHUs. Access to health services was analyzed based on the
      socio-organizational and geographic characteristics and according to the demand
      for medical appointments. Over 50% of respondents sought the service of FHUs and
      of these 78.7% reported attending the appointment. With respect to organizational
      access, problems were encountered, such as long waiting times for consultation.
      Geographical barriers were ascertained in the use of FHUs, but these did not
      prevent the realization of medical consultation. The use of FHUs was higher among
      people with lower socioeconomic status.

PMID- 23175312
TI  - [Access to dental care during prenatal assistance].
AB  - This study sought to evaluate the self-perceived response to dental care during
      prenatal assistance in the Unified Health System (SUS) in the Metropolitan Region
      of Vitoria, Espirito Santo, Brazil. 1032 postpartum women were interviewed and
      1006 prenatal records copied. Postpartum women's self-perceived response was
      measured by the Oral Health Index Profile-14. When an impact was identified,
      dental care rendered in educational, preventive and curative terms was considered
      adequate. When there was no impact, assistance was considered adequate in
      educational and preventive terms. The Chi-square test revealed an association
      between prenatal care and dental care. Oral health impact on quality of life was
      14.7%. Dental care received by mothers in educational terms was rated at 41.3%,
      while in preventive terms it was 21% and in curative terms it was 16.6%. Six or
      more prenatal appointments coupled with educational activities was closely
      associated with adequate dental care (p < 0.05). Access to dental care is
      facilitated when pregnant women attend health services and become involved in
      educational activities during the prenatal period. Consequently, educational
      measures appear to indicate an improvement in prenatal care in the SUS.

PMID- 23175313
TI  - [Access and comprehensiveness: the viewpoint of users of a mental health
      network].
AB  - This article analyzes user viewpoints regarding mental health care, with a focus
      on comprehensiveness and access at Psychosocial Care Centers (PCCs). It is a
      qualitative study with theoretical and methodological references of the Fourth
      Generation Evaluation and application of the Hermeneutic Dialectic Circle
      technique. Twelve users of ten mental health services in Fortaleza were
      interviewed from March to May 2011. Themes of the study were grouped from the
      narratives, with the hermeneutics of Paul Ricoeur as the benchmark for analysis.
      The thematic categories were: viewpoints on mental healthcare; conflicts between
      supply and the subjective need to receive; similarities and differences: from
      tutelage to autonomy; absence and belonging: open PCCs and non-community centers;
      between stigma and humanization. The main findings are: the PCCs are seen as
      spaces for conviviality able to establish affective and social networks; stigma,
      prejudice and tutelage are present in the services, in their families and in the
      community; asylum practices persist in alternative services; the humanization of
      care extends access and bonding in the services; the trajectory of users of the
      Unified Health System occurs due to their social and health needs.

PMID- 23175314
TI  - [Delay in the search for health services for the diagnosis of tuberculosis in
      Ribeirao Preto, Sao Paulo].
AB  - The scope of this paper is to analyze delays in locating health services for the
      diagnosis of tuberculosis in Ribeirao Preto in 2009. An epidemiological and cross
      sectional study was conducted with 94 TB patients undergoing treatment. A
      structured questionnaire, based on the Primary Care Assessment Tool adapted for
      TB care was used. A median (15 days or more) was established to characterize
      delay in health attendance. Using the Prevalence Ratio, the variables associated
      with longer delay were identified. The first healthcare services sought were the
      Emergency Services (ES) (57.5%). The longest period between seeking assistance
      occurred among males, aged between 50 and 59, who earned less than five minimum
      wages, had pulmonary TB, were new cases, were not co-infected with TB/HIV, did
      not consume alcohol, had satisfactory knowledge about TB before diagnosis (with a
      statistically significant association with delay) and who did not seek healthcare
      close to home before developing TB. There is a perceived need for training
      healthcare professionals about the signs and symptoms of the disease, reducing
      barriers of access to timely diagnosis of TB and widely disseminating it to the
      community in general.

PMID- 23175315
TI  - [Routes to care--the itineraries of people living with HIV].
AB  - Living with HIV infection is currently chronic but manageable. Therefore, it is
      important to consider the implications of individual trajectories of seeking care
      for the disease in the daily life of its carriers. These trajectories are in the
      routes followed by users seeking answers to their illness. This qualitative study
      sought to analyze the therapeutic itinerary of people living with HIV/AIDS. The
      subjects studied were men and women with HIV attended in a Specialized Healthcare
      unit and the University Hospital, both public services located in a municipality
      of Minas Gerais state, Brazil. The participants were approached through
      interviews and data were analyzed using the thematic analysis technique. From the
      individual routes that permeated these narratives, the itineraries of individuals
      living with HIV emerged. These covered topics such as being sent from place to
      place and finally discovering how to enter the care system, the implications of
      cost and access, management of treatment and the importance of affiliation bonds.
      These questions that oriented the work made it possible to infer the strengths
      and weaknesses in the healthcare service to the HIV carrier, by considering the
      personal experience of these individuals.

PMID- 23175316
TI  - [Evaluation of the pre-test counseling process in the HIV Testing and Counseling
      Centers in Rio de Janeiro State: the perception of users and health
      professionals].
AB  - This study sought to evaluate the pre-test counseling process in the HIV Testing
      and Counseling Centers (CTA) in Rio de Janeiro State, based on the perceptions of
      users and health professionals. A population survey was performed, based on a
      structured questionnaire given to a sample of users and counselors of nine CTAs.
      Quantitative analyses were employed to evaluate the degree of satisfaction in
      relation to infrastructure indicators of the way patients are received and
      treated, the user-counselor relationship, and territoriality, accessibility and
      availability. Among the CTA users interviewed, 58.1% were very satisfied and
      38.7% were satisfied with the care received, according to analysis of set of
      indicators. The majority of health professionals (80.9%) interviewed also
      declared their satisfaction. Despite the high level of satisfaction, some
      complaints regarding structural and procedural aspects were identified, which
      call for the attention of the health managers and professionals for the
      enhancement of the quality of the service rendered.

PMID- 23175317
TI  - [Characteristics of the access and utilization of public dental services in
      medium-sized cities].
AB  - This cross-sectional study sought to describe the main characteristics of access
      and utilization of primary and specialized public dental services in two medium
      sized cities in Bahia with 100% coverage of the Family Health Program. A survey
      of 952 households and 2.539 individuals aged over 15 years was conducted. The
      main variables analyzed were: perceived oral health needs, demand for the
      service, barriers of organizational access and the type of service and procedure
      utilized. The use of specialized public dental services was of 11.7% and primary
      care was 26%. In the city where there was greater use of public dental services,
      there was less use of private services. The main barrier to access remained in
      primary care (from 5.0% to 15.2%). There was little interface between secondary
      care a primary care, as only 16.6% of users returned to this level of care. In
      conclusion, the main barrier to access in cities with specific organizational and
      geographic realities appears to be in primary dental care. Individual preventive
      actions were little reported. It is recommended that barriers to access in
      primary care be eliminated, and also that a protocol (clinical guides) be
      established to foster the continuity and longitudinality of primary dental care.

PMID- 23175319
TI  - [Care for patients with Chronic Kidney Disease at the primary healthcare level:
      considerations about comprehensiveness and establishing a matrix].
AB  - Chronic kidney disease is a public health problem throughout the world. Early
      detection and treatment can reduce morbidity, mortality and associated
      expenditures. The objective of this research is to examine primary healthcare
      from a physician's perspective, evaluating the patient's access to other levels
      of healthcare. Questionnaires were given to 62 family physicians working in
      primary healthcare units in the city of Fortaleza. Glomerular filtration rate was
      measured by only 8.1% of the physicians when evaluating patients with diabetes
      and 4.8% when evaluating hypertensive patients. The majority of physicians
      (51.2%) refer patients with slight/moderate Glomerular filtration rate reduction
      to a nephrologist. On the other hand, 25.8% do not refer patients with advanced
      chronic kidney disease reduction to a specialist. The gap between these levels of
      healthcare creates a barrier to user access, prejudicing comprehensive
      healthcare. The creation of new work processes is urgently required and the
      matrix process is a viable option to connect these healthcare levels for the care
      of patients with chronic kidney disease or its main risk factors (diabetes and
      arterial hypertension).

PMID- 23175318
TI  - [Characteristics of consultation and mothers' satisfaction in primary care for
      children under 5 years of age, Fortaleza, Brazil].
AB  - The scope of this study is to describe aspects related to the dimensions of
      access, the service characteristics and factors associated with satisfaction of
      mothers in the city of Fortaleza, Ceara. It is an observational, cross-sectional
      population-based study conducted in 2008 in Fortaleza, Ceara. Families with at
      least one child under 5 years of age living at home and who were users of the
      Unified Health System (SUS) were included, The Pearson chi-square test, and when
      appropriate the Fisher exact test, were used for the statistical associations.
      The study included 350 families. Most reasons given for the consultation was
      sickness and on a larger scale, performed by physicians; 2/3 of mothers reported
      having been satisfied with the last service received by the child. The main
      factors associated with satisfaction were: the doctors who treated the
      mother/child called them by name, the service was given on the day that the
      mother needed and the waiting room of the unit had entertainment. Access to
      primary care was well evaluated. The satisfaction of users is related to the
      relationship established with health professionals, however the organization of
      the service and infrastructure of the units are still considered weak points.

PMID- 23175321
TI  - GSTM1 polymorphism modifies the effect of smoking on calcaneal quantitative
      ultrasound in young men.
AB  - Evidence suggests that smoking adversely affects bones. Glutathione S
      transferases (GSTs) are important in the detoxification of tobacco smoke
      compounds. This study investigated the influence of GSTM1 and GSTT1 genetic
      polymorphisms on the effects on bone induced by tobacco smoking in young men. In
      total, 231 Chinese men aged 20-39 years were assessed by a cross-sectional study.
      Calcaneal quantitative ultrasound (QUS) was measured. Smoking information was
      obtained using a questionnaire. Genotypes were determined for null alleles of
      GSTM1 and GSTT1. Smoking was inversely associated with speed of sound (SOS) and
      bone quality index (BQI) among subjects with GSTM1 null genotype (beta = -0.28,
      95% CI, -34.01 to -8.65 and beta = -0.30, 95% CI, -16.41 to -4.49, respectively),
      but not among those with the allele present (beta = -0.02, 95% CI, -15.01 to
      12.59 and beta = -0.09, 95% CI, -8.75 to 3.02, respectively). P for interaction =
      0.04 for SOS and 0.08 for BQI. No interaction was found between the GSTT1
      polymorphism and smoking. The results showed that GSTM1 deficiency may increase
      the adverse effect of smoking on calcaneal QUS in young men, suggesting an
      interaction between metabolic genes and tobacco smoke in bone detoxification.

PMID- 23175322
TI  - Cationic closo-carboranes 2. Do computed 11B and 13C NMR chemical shifts support
      their experimental availability?
AB  - (11)B and (13)C NMR spectra of so-far experimentally unknown carbon-rich cationic
      closo-carboranes C(3)B(n-3)H(n)(+) (n = 5, 6, 7, 10, 12) have been calculated at
      the GIAO-MP2 level and subsequently analyzed to reveal the nature of bonding in
      these potentially weakly coordinating cations. All previous rules derived for
      understanding (11)B NMR spectra of borane derivatives can be applied to
      realistically account for the corresponding shieldings. The correlated
      wavefunction for n = 5 and, to a lesser extent, for n = 10 seems to be decisive
      when trying to compute realistic shielding tensors, which is in agreement with
      the corresponding known dicarbaboranes. For other cluster dimensions
      noncorrelated wavefunctions also work well, in particular in relation to the
      corresponding dicarbaboranes. All these observations strongly support the fact
      that experimental availability of these unique clusters is possible.

PMID- 23175324
TI  - [Gap junction involvement in hippocampal theta rhythm generation].
AB  - Hippocampal theta rhythm is probably the best example of oscillations and
      synchrony phenomena occurring in neuronal networks of the central nervous system.
      It is well known that intraneuronal communication via chemical and electrical
      synapses underlies these oscillatory processes. Despite well-documented knowledge
      concerning the participation of chemical transmission in production of theta
      activity, the role of much faster gap junction communication is still not fully
      understood. This paper provides an overview of current research data concerning
      the involvement of electrical transmission in generation of the best synchronized
      EEG pattern recorded from the mammalian brain--theta rhythm.

PMID- 23175323
TI  - Is there an effect of folic acid supplementation on the coagulation factors and C
      reactive protein concentrations in subjects with atherosclerosis risk factors?
AB  - INTRODUCTION: Folic acid (FA) may delay the formation of atherosclerotic lesions.
      Increased plasma levels of von Willebrand factor (VWF) are observed in
      cardiovascular disease, which leads to higher risk of thrombosis. Fibrinogen (Fb)
      is a well-documented risk factor of cardiovascular disease. The aim of this study
      was to analyze the effect of FA supplementation on the Fb, VWF and C-reactive
      protein (CRP) plasma concentrations in subjects with atherosclerosis risk
      factors. MATERIAL/METHODS: The study enrolled 124 Caucasian individuals (60 M, 64
      F) with atherosclerosis risk factors--family history of premature ischaemic
      stroke, arterial hypertension, dyslipidaemia, overweight and obesity, cigarette
      smoking and low physical activity. The participants were asked to take FA in the
      low dose of 0.4 mg/24 h for three months. RESULTS: After FA supplementation a
      significant reduction of the VWF concentrations in females (76.6 vs 72.3%;
      p=0.028) and in males (75.5 vs 66.9%; p=0.001) was observed. Among women and men
      with dyslipidaemia concentrations of VWF decreased after FA supplementation
      (76.8% vs 69.6%; p=0.003 and 76.7% vs 67.8%; p=0.001 respectively). Among females
      and males with BMI >=25 kg/m2 concentrations of VWF decreased only in men (77.6%
      vs 66.5%; p=0.001). In female and male smokers supplementation of FA decreased
      VWF concentrations (82.5% vs 74.4%; p=0.012 and 76.6% vs 69.5%; p=0.036
      respectively). DISCUSSION: The results of our study suggest that there is an
      effect of FA supplementation on VWF concentrations in subjects with
      atherosclerosis risk factors.

PMID- 23175325
TI  - Patient's perception of the meaning of life in cystic fibrosis--its evaluation
      with respect to the stage of the disease and treatment.
AB  - INTRODUCTION: Cystic fibrosis (CF) is related to physical and mental barriers.
      The objective of this work was to evaluate and compare patients' perception of
      sense of life in cystic fibrosis in different stages of their disease and
      therapeutic methods. MATERIAL/METHODS: The study group included 45 patients
      divided into 3 subgroups: after lung transplantation, waiting for lung
      transplantation and with cystic fibrosis in stable condition. The evaluation and
      comparison of patient's perception of sense of life and purpose of life was
      performed with the Purpose in Life Test. RESULTS: All patients with CF felt their
      lives were meaningful and purposeful. However, their pursuits for designated aims
      depended on the progression of their disease. CONCLUSIONS: CF with its poor
      prognosis has a significant impact on patient's hierarchy of respected values and
      life priorities. High level of acceptance for suicidal behaviours observed in all
      diagnostic subgroups of patients with CF indicates a need for organized
      intensified psychological care.

PMID- 23175326
TI  - [Cinacalcet therapy and cardiovascular risk in hemodialysis patients].
AB  - Patients with end-stage kidney disease are at high cardiovascular risk due to
      accelerated atherosclerosis development. Important factors that accelerate the
      development of atherosclerosis in this group are calcium-phosphorus disturbances
      causing vascular calcification. Therefore, slowing the development and
      progression of vascular calcification is a novel therapeutic target in the
      treatment of calcium and phosphorus disturbances associated with chronic kidney
      disease. It seems that cinacalcet, a calcimimetic of the second generation, used
      in patients with refractory secondary hyperparathyroidism can slow the
      progression of vascular calcification and potentially reduce the cardiovascular
      risk. This paper reviews the current literature on the pathogenesis of vascular
      calcification and the potential impact of cinacalcet to reduce cardiovascular
      risk in patients with end-stage kidney disease.

PMID- 23175327
TI  - Type of serum influences the rituximab dependent cytotoxicity and apoptosis of
      chronic lymphocytic leukemia cells in vitro.
AB  - PURPOSE: The aim of the study was to compare the influence of types of serum on
      the in vitro viability and on either spontaneous or rituximab (RIT)-induced
      apoptosis of chronic lymphocytic leukemia (CLL) cells. METHODS: The influence of
      fetal calf serum (FCS), patients' autologous serum (AS) and human AB-serum (ABS),
      used alone and in combinations consisting of two of them (v/v-1:1), on RIT
      dependent cytotoxicity, apoptosis, detection of active forms of caspases-3,-9,-8
      and disruption of mitochondrial membrane potential (DeltaPsim) were assessed by
      flow cytometry. RIT was used at the concentration of 10 ug/ml. The spontaneous
      apoptosis was assessed in culture without RIT. RESULTS: AS revealed the
      protective action on CLL cells, however this serum added in vitro to the culture
      either alone or in combination with FCS was the only one to allow RIT to exert
      its cytotoxic action against CLL cells. RIT-induced apoptosis involved changes in
      DeltaPsim and activation of caspases-3,-8,-9 when AS+FCS was applicated. Drug
      induced apoptosis (DIA) was 6.02 and 0.34, when FCS+AS and FCS alone were used,
      respectively (p<0.01). The RIT-dependent cytotoxic effect decreased when FCS+AS
      or FCS+ABS were used, as compared to effect of AS used separately. The cytotoxic
      effect of RIT did not depend on drug concentration, but on the type of serum
      added to the culture. CONCLUSIONS: The strongest cytotoxic effect of RIT in the
      presence of AS suggests that this drug activity towards CLL cells is enhanced by
      known cytotoxic mechanisms, caspase-dependent apoptotic pathway and possible
      influence of other extracellular factors present in the patients' sera.

PMID- 23175328
TI  - [Mast cell inhibitory receptors].
AB  - Mast cells play an important role in diverse physiological mechanisms as well as
      taking part in antimicrobial defense. What is more, these cells are important
      regulators of a number of pathophysiological processes, involving allergic
      reactions. Therefore, it seems to be very important to know and understand the
      factors and receptors influencing mast cell activity. Nowadays it is well
      established that activating signals are counterbalanced by negative or inhibition
      signals transmitted by inhibitory receptors containing immunoreceptor tyrosine
      based inhibitory motifs (ITIMs). Inhibitory receptor engagement leads to ITIM
      tyrosine phosphorylation, the recruitment and activation of protein tyrosine
      phosphatases such as SHP-1, SHP-2 and/or SHIP, and the dephosphorylation of
      activating receptor associated proteins. There is growing evidence that a number
      of inhibitory receptors have been identified on mast cells. The scope of this
      paper is to present the current knowledge on mast cell-associated inhibitory
      receptors, such as FcgammaRIIB, paired immunoglobulin-like receptor B (PIR-B),
      CD300, CD172a, gp49B1, CD200R, sialic acid-binding immunoglobulin-like lectin
      (Siglec) molecules, CD305, allergin-1, mast cell function-associated antigen
      (MAFA), and CD72. The role of these inhibitory receptors in regulation mast cell
      activity is also discussed.

PMID- 23175329
TI  - Accuracy of rapid influenza diagnostic test and immunofluorescence assay compared
      to real time RT-PCR in children with influenza A(H1N1)pdm09 infection.
AB  - INTRODUCTION: The influenza burden among children is underestimated. The aim of
      our study was to estimate the accuracy of the rapid influenza detection test
      (RIDT) BD DirectigenTM EZ Flu A+B(r) and direct immunofluorescence assay (DFA)
      used among children with influenza-like illness (ILI) consulted in the ambulatory
      care clinic. MATERIAL/METHODS: A total of 150 patients were enrolled in the
      study. Inclusion criteria were: age less than 59 months, presentation of ILI
      according to the CDC (Centers for Disease Control and Prevention) definition
      (fever >37.8 degrees C, cough and/or sore throat in the absence of another known
      cause of illness), duration of symptoms shorter than 96 hours. Two nasal swabs
      and one pharyngeal swab were obtained from patients and tested by RIDT, DFA and
      real time RT-PCR as the reference method. RESULTS: For influenza A (H1N1)pdm09
      virus sensitivity of RIDT was 62.2% (95% CI 46.5-76.2%), specificity 97.1% (95%
      CI 91.8-99.4%), PPV 90.3% (95% CI 74.3-98%), NPV 85.7% (95% CI 78.1-91.5%), for
      DFA sensitivity was 60% (95% CI 51.9-63.2%), specificity 96% (95% CI 88.7-98.8%),
      PPV 93.1% (95% CI 80.5-98%), NPV 72.7% (95% CI 67.2-74.9%). Analysis of logistic
      regression revealed that the chance of receiving a true positive result of RIDT
      was twice as high when the test was conducted during the first 48 hours of
      symptoms (OR 0.40 vs OR 0.22). CONCLUSIONS: The accuracy of RIDT is comparable
      with DFA and both methods are very specific but moderately sensitive in diagnosis
      of influenza in young children. Both methods may be recommended for screening for
      influenza among children.

PMID- 23175330
TI  - [Potential pathogens in multiple sclerosis (MS)].
AB  - Multiple sclerosis is a neuroimmunological disease in which etiologic agents
      have not been identified yet. The etiology of MS is complex in its nature and may
      involve many different agents acting simultaneously or in a cascade manner
      leading to the development of the disease. The causes of MS development were
      sought among the factors associated with HLA and TCR genes and human endogenous
      retroviruses (HERV). Environmental factors such as bacterial, fungal and viral
      infections as well as potential participation of vitamin D in the pathogenesis of
      the disease have also been examined. The current state of knowledge concerning
      potential factors participating in the etiopathogenesis of multiple sclerosis has
      been reviewed in this paper.

PMID- 23175331
TI  - [Narcolepsy: etiology, clinical features, diagnosis and treatment].
AB  - Narcolepsy is a chronic hypersomnia characterized by excessive daytime
      sleepiness (EDS) and manifestations of disrupted rapid eye movement sleep stage
      (cataplexy, sleep paralysis, and hypnagogic/hypnopompic hallucinations).
      Mechanisms underlying narcolepsy are not fully understood. Experimental data
      indicate that the disease is caused by a loss of hypocretin neurons in the
      hypothalamus, likely due to an autoimmune process triggered by environmental
      factors in susceptible individuals. Most patients with narcolepsy and cataplexy
      have very low hypocretin-1 levels in the cerebrospinal fluid. An appropriate
      clinical history, polysomnogram, and multiple sleep latency test are necessary
      for diagnosis of the disease. Additionally, two biological markers, i.e.,
      cerebrospinal fluid hypocretin-1 levels and expression of the DQB1*0602 gene, are
      used. The treatment of narcolepsy is aimed at the different symptoms that the
      patient manifests. Excessive daytime sleepiness is treated with psychostimulants
      (amphetamine-like, modafinil and armodafinil). Cataplexy is treated with sodium
      oxybate (GHB), tricyclic antidepressants, or selective serotonin and
      noradrenaline reuptake inhibitors. Sleep paralysis, hallucinations, and
      fragmented sleep may be treated with sodium oxybate. Patients with narcolepsy
      should follow proper sleep hygiene and avoid strong emotions.

PMID- 23175332
TI  - Antibacterial activity of selected standard strains of lactic acid bacteria
      producing bacteriocins--pilot study.
AB  - INTRODUCTION: In this paper, an attempt was made to evaluate the antibacterial
      potential of standard strains of lactic acid bacteria (LAB) producing
      bacteriocins of various classes, thus demonstrating various mechanisms of cell
      membrane damages against the Streptococcus agalactiae strains (Group B
      Streptococcus, GBS), depending on surface polysaccharides and surface alpha-like
      protein genes. MATERIALS/METHODS: Antimicrobial property of the strains of L.
      plantarum C 11, L. sakei DSMZ 6333, and L. lactis ATCC 11454 producing
      bacteriocins: JK and EF plantaricins, sakacin and nisin, respectively, against
      the GBS strains was evaluated. The chosen to the study GBS strains were
      represented by serotypes Ia, Ib, II, III, V and they had bca, epsilon, rib, alp2
      or alp3 alpha-like protein genes. The experiment was conducted by means of
      suspension culture and the bacteria count was determined using the serial
      dilution method. RESULTS: A great ability of L. plantarum C 11 strain was proven
      to inhibit the GBS growth. The strain of L. sakei DSMZ 6333 did not demonstrate
      any ability to inhibit the growth of GBS, whereas L. lactis ATCC 11454 inhibited
      the growth of S. agalactiae indicator strains to a minor extent. Statistically
      significant differences were demonstrated between the GBS strains representing
      various serotypes against the antimicrobial activity of model LAB strains. The
      least sensitive to the activity of bacteriocins were the strains representing
      serotypes Ib and III, whereas the strains representing serotype II were the most
      sensitive. The sensitivity of the GBS strains to the antimicrobial activity of
      LAB was not dependent on alpha-like protein genes. DISCUSSION: Among the LAB
      standard strains producing bacteriocins, the strongest antimicrobial property was
      observed in the strain of L. plantarum C 11. Because of the generally known and
      verified strong antagonistic property of the strains of L. plantarum species
      against indicator bacteria, it is necessary to further pursue the research
      presented in this paper.

PMID- 23175333
TI  - Role of ghrelin and leptin in the regulation of carbohydrate metabolism. Part I.
      Ghrelin.
AB  - Ghrelin is a polypeptide that is excreted by the secretory cells of the gastric
      and intestinal mucosa, the arcuate nucleus of the hypothalamus as well as by the
      epsilon cells (epsilon) located in the pancreatic islets. It plays an important
      role in maintaining the energy balance of the organism and influences the
      endocrine function of the pancreas and glucose metabolism. It takes part in the
      regulation of glucose homeostasis through the modulation of insulin secretion and
      insulin sensitivity.    Due to the broad spectrum of ghrelin's biological
      effects, ways to modify them are presently being investigated. Much attention is
      focused on the enzyme called ghrelin O-acyl transferase (GOAT), which mediates
      the physiological functions of ghrelin. Acyl-ghrelin and des-acyl-ghrelin appear
      to have opposite glucoregulatory effects. The regulation of acylation by GOAT
      seems therefore to play a role in mediating glucose metabolism. The modulation of
      GOAT or ghrelin signaling may be a clinically relevant strategy to treat obesity
      and metabolic diseases such as type 2 diabetes.   

PMID- 23175334
TI  - Role of ghrelin and leptin in the regulation of carbohydrate metabolism. Part II.
      Leptin.
AB  - Leptin is produced by mature adipocytes. Its amount correlates positively with
      the mass of the adipose tissue. Leptin plays a crucial role in maintaining body
      weight and glucose homeostasis. It is transported through the blood-brain barrier
      to the central nervous system, where it activates the autonomic nervous system,
      causing the feeling of satiety and inhibiting appetite. It also acts through
      central and peripheral pathways, including the regulation of insulin secretion by
      pancreatic beta cells. Leptin may also directly affect the metabolism and
      function of peripheral tissues. It has been found to play a role in peripheral
      insulin resistance by attenuating insulin action, and perhaps also insulin
      signaling, in various insulin-responsive cell types. Recent data provide
      convincing evidence that leptin has a beneficial influence on glucose
      homeostasis. Studies suggest that leptin could be used as an adjunct of insulin
      therapy in insulin-deficient diabetes, thereby providing an insight into the
      therapeutic implications of leptin as an anti-diabetic agent. Extensive research
      will be needed to determine long-term safety and efficacy of such a therapy.

PMID- 23175335
TI  - [Glycation of extracellular matrix proteins and its role in atherosclerosis].
AB  - Glycation consists in formation of advanced glycation end-products (AGE) during
      non-enzymatic reaction between reducing sugars and proteins, lipids or nucleic
      acids. This review is focused mainly on glycation of collagen and its role in
      acceleration of vascular disease. Collagen is an extracellular matrix protein
      characterized by unique structure forming fibrils with great anti-tensile and
      anti-breaking strength. The protein builds the connective tissue and is
      responsible for biomechanical properties of blood vessels. It is reported that
      higher content of glycated collagen correlates with lower elasticity and greater
      toughness of the vessel walls and, as a consequence, a faster rate of
      atherosclerosis development. Numerous mechanisms connected with AGE formation are
      involved in atherogenesis, among others: receptor-mediated production of free
      radicals, triggering an inflammatory process, activation of leukocytes and
      thrombocytes, facilitation of LDL binding, change in level of growth factors,
      adhesion molecules, MMP and some other proteins' expression. The coverages allow
      the development of therapeutic strategies to prevent or slow down the
      pathological processes connected with glycation of collagen and other proteins in
      the artery wall. The main strategies are based on limitation of exogenous AGE,
      consumption of products which contain rutin, treatment with drugs which inhibit
      AGE formation, such as  pyridoxamine, and chemicals which are able to cleave
      already formed AGE protein-protein crosslinks, such as ALT-711.

PMID- 23175336
TI  - Role of cytoskeletal motor proteins in viral infection.
AB  - Cytoskeleton, composed of actin filaments, microtubules and intermediate
      filaments, regulates many processes in the cell, e.g. intracellular transport.
      Actin and microtubules are polarized structures, along which bidirectional
      transport of motor proteins occurs: myosins along actin and the dynein/dynactin
      complex and kinesins along microtubules. Viruses interact with the cytoskeleton
      and motor proteins at different stages during their replication cycle. When
      entering and egressing the cell, viruses must penetrate the cortical layer of
      microfilaments, which usually takes place with the contribution of myosin. In the
      cytoplasm, retrograde transport involving dynein is used to move viruses to the
      microtubule organizing center. After replication, kinesins participate in
      anterograde transport of newly produced virions to the peripheral region, close
      to the plasma membrane. Some families of viruses have developed alternate routes
      of intracellular transport.    The aim of this study is to describe the
      interactions between virus and cytoskeletal motor proteins and to determine their
      role in viral infection according to the current literature data.   

PMID- 23175337
TI  - [Risk factors for skin cancer development in patients after organ
      transplantation].
AB  - Cancer has become the second most common cause of death in patients after organ
      transplantation. Among all cancers arising de novo after transplantation skin
      cancers are the most common, accounting for 95% of all skin neoplasms.    Due to
      the significantly higher morbidity, aggressive, rapid progression of cancer and
      unfavorable prognosis, the population requires a specific oncological approach.
      Therefore, special attention should be paid to factors predisposing to the
      development of cancer, including skin cancer, in patients after organ
      transplantation. Some of these factors are well understood, while the role of
      others is still ambiguous. Among the etiological factors mentioned are those that
      are associated with the recipient. These include genetic factors such as male
      sex, fair skin and inability to be tanned, and compatibility of the HLA system,
      and non genetic factors such as patient age, chronic skin ulcers and scars, the
      type of transplanted organ, immunosuppression, and particularly the type and
      cumulative doses of drugs. In addition, the pathogenesis of cancer is influenced
      by environmental factors such as exposure to sunlight and therefore latitude,
      ionizing radiation, chemical carcinogens and viral infections.    Knowledge of
      etiological factors and mechanisms of etiopathogenesis allow for indication and
      observation of patients with increased risk of cancer as well as faster healing
      in these patients.   

PMID- 23175338
TI  - Bystander effect induced by UV radiation; why should we be interested?
AB  - The bystander effect, whose essence is an interaction of cells directly subjected
      to radiation with adjacent non-subjected cells, via molecular signals, is an
      important component of ionizing radiation action. However, knowledge of the
      bystander effect in the case of ultraviolet (UV) radiation is quite limited.
      Reactive oxygen and nitrogen species generated by UV in exposed cells induce
      bystander effects in non-exposed cells, such as reduction in clonogenic cell
      survival and delayed cell death, oxidative DNA damage and gene mutations,
      induction of micronuclei, lipid peroxidation and apoptosis. Although the
      bystander effect after UV radiation has been recognized in cell culture systems,
      its occurrence in vivo has not been studied. However, solar UV radiation, which
      is the main source of UV in the environment, may induce in human dermal tissue an
      inflammatory response and immune suppression, events which can be considered as
      bystander effects of UV radiation. The oxidative damage to DNA, genomic
      instability and the inflammatory response may lead to carcinogenesis. UV
      radiation is considered one of the important etiologic factors for skin cancers,
      basal- and squamous-cell carcinomas and malignant melanoma. Based on the
      mechanisms of actions it seems that the UV-induced bystander effect can have some
      impact on skin damage (carcinogenesis?), and probably on cells of other tissues.
      The paper reviews the existing data about the UV-induced bystander effect and
      discusses a possible implication of this phenomenon for health risk. 

PMID- 23175339
TI  - Utility of transperineal and anal ultrasonography in the diagnostics of
      hidradenitis suppurativa and its differentiation from a rectal fistula.
AB  - INTRODUCTION: The pathogenesis of hidradenitis suppurativa (HS) is not fully
      understood. There exist several theories, in which mechanical factors, genetic
      factors, as well as immunological dysfunction of lymphocytes are suspected.
      Clinically, this entity is frequently mistaken for anal fistula with consequently
      wrong treatment. We aim to determine the utility of transperineal ultrasound
      (TPUS) and anal ultrasound (AUS) in the diagnosis of HS and its differentiation
      from an anal fistula. MATERIAL/METHODS: Retrospective analysis was performed on
      51 patients (5 females, 46 males) aged 20-71 years (mean age 47.5), who were
      operated on in the years 2006-2011 for HS in the area of the anus and perineum,
      and pre-operatively had been imaged with TPUS and AUS. Sixty-seven operations
      were analyzed, as 11 patients were operated on more than once due to HS
      recurrence. RESULTS: In 66 out of 67 cases (98.5%), the pre-operative TPUS and
      AUS were in accordance with the intraoperative findings. Only in 1 patient was a
      pilonidal cyst diagnosed intraoperatively. In all 67 patients, the TPUS showed
      typical fluid-solid changes localized in the subcutaneous adipose tissue. In 6
      out of 67 cases of HS (8.9%) AUS showed an anal fistula coexisting with the HS.
      In 2 cases (2.9%) a skin malignancy coexisting with HS was found. DISCUSSION:
      TPUS is an accessible imaging method, which confirms the typical localization of
      changes of HS, and together with AUS it allows for the proper differentiation of
      HS from an anal fistula or an abscess.

PMID- 23175340
TI  - Investigations of seborrheic dermatitis. Part I. The role of selected cytokines
      in the pathogenesis of seborrheic dermatitis.
AB  - INTRODUCTION: The etiology of seborrheic dermatitis is not fully understood. It
      has been observed that a number of anascogenic yeasts of Malassezia spp. is
      related to the intensity of the symptoms. The aim of the study is to measure the
      concentration of selected inflammatory factors IL-2, IL-4, IFN-gamma and TNF
      alpha in the serum by an immunoenzymatic method, as well as to confirm the
      relationship between the studied factors and the clinical condition of the
      patients (sex, the intensity of skin lesions according to the Scaparro scale)
      and, finally, to compare the results with the control group. MATERIAL/METHODS:
      The total number of subjects who participated in the study was 66. The control
      group (C) consisted of 30 volunteers (23 females and 7 males), with no clinical
      disorders, aged 24-65 (37.41+/-6.08 years). Thirty-six patients with seborrheic
      dermatitis (16 females and 20 males), aged 19-76 (38.61+/-13.77), made up the
      study group. The determination of IL-2, IL-4, IFN-gamma and TNF-alpha was
      performed by ELISA using a Human High Sensitivity kit (Diaclone, France).
      Clinically, the intensity of the disease process was evaluated on the Scaparro et
      al. scale, as modified by Kaszuba. RESULTS: We observed statistically
      significantly higher levels of IL-2 and IFN-gamma in patients with seborrheic
      dermatitis compared to the control group. CONCLUSIONS: We conclude that
      seborrheic dermatitis is a dermatosis characterized by a cell type immune
      response with an important role of IFN-gamma and IL-2.

PMID- 23175341
TI  - Investigations of seborrheic dermatitis. Part II. Influence of itraconazole on
      the clinical condition and the level of selected cytokines in seborrheic
      dermatitis.
AB  - INTRODUCTION: The pathogenesis of seborrheic dermatitis has not been fully
      elucidated. A number of anascogenic yeasts of Malassezia spp. appear to be
      involved in the intensity of the symptoms. The purpose of the study is to
      evaluate the levels of selected inflammatory cytokines, IL-2, IL-4, IFN-gamma and
      TNF-alpha, in the serum after treatment with itraconazole. MATERIAL/METHODS:
      Sixty-six subjects were enrolled in the study. The control group consisted of 30
      participants (23 females and 7 males) without any clinical disorders, aged 24-65
      (37.41+/-6.08 years). Thirty-six patients with seborrheic dermatitis (16 females
      and 20 males), aged 19-76 (38.61+/-13.77), constituted the study group. The
      measurement of IL-2, IL-4, IFN-gamma and TNF-alpha levels was performed by ELISA
      using a Human High Sensitivity kit (Diaclone, France). RESULTS: After six-week
      treatment with itraconazole administered daily at a dose of 200 mg using pulse
      therapy, there was remission of the disease or at least substantial clinical
      improvement in the patients with seborrheic dermatitis. The levels of IL-2 and
      IFN-gamma cytokines in the study group were higher than in the control group.
      After the treatment the level of IFN-gamma secretion in the male patients with
      seborrheic dermatitis significantly increased. The levels of the other studied
      cytokines did not significantly differ. CONCLUSIONS: The treatment with
      itraconazole had a beneficial effect on the clinical condition of the skin of the
      patients. IFN-gamma is a cytokine whose secretion might affect the condition of
      the skin in seborrheic dermatitis.

PMID- 23175342
TI  - [Individualization of anticancer therapy; molecular targets of novel drugs in
      oncology].
AB  - Deregulation of cellular signal transduction, caused by gene mutations, has been
      recognized as a basic factor of cancer initiation, promotion and progression.
      Thus, the ability to control the activity of overstimulated signal molecules by
      the use of appropriate inhibitors became the idea of targeted cancer therapy,
      which has provided an effective tool to normalize the molecular disorders in
      malignant cells and to treat certain types of cancer. The molecularly targeted
      drugs are divided into two major pharmaceutical classes: monoclonal antibodies
      and small-molecule kinase inhibitors. This review presents a summary of their
      characteristics, analyzing their chemical structures, specified molecular
      targets, mechanisms of action and indications for use. Also the molecules
      subjected to preclinical trials or phase I, II and III clinical trials evaluating
      their efficiency and safety are presented. Moreover, the article discusses
      further perspectives for development of targeted therapies focusing on three
      major directions: systematic searching and discovery of new targets that are
      oncogenic drivers, improving the pharmacological properties of currently known
      drugs, and developing strategies to overcome drug resistance. Finally, the role
      of proper pharmacodiagnostics as a key to rational anticancer therapy has been
      emphasized since the verification of reliable predictive biomarkers is a basis of
      individualized medicine in oncology. 

PMID- 23175343
TI  - [Role of sphingolipids in digestive system].
AB  - Present in the digestive system, sphingolipids are responsible for multiple
      important physiological and pathological processes. On the membrane of intestinal
      epithelial cells sphingolipids contribute to structural integrity, regulate
      absorption of nutrients and may act as receptors for some microorganisms and
      their toxins. Moreover, bioactive lipid messengers such as ceramide and
      sphingosine-1-phosphate influence cellular growth, differentiation and programmed
      cell death, apoptosis. Further studies are needed to fully explore the clinical
      implications of sphingolipids in neoplastic and inflammatory diseases in the
      gastrointestinal tract. Pharmacological compounds which regulate metabolism of
      sphingolipids can be potentially useful in treatment of colon cancer,
      inflammatory bowel diseases or nonalcoholic fatty liver disease. The aim of this
      work is to present a critical review of the physiological and pathological role
      of sphingolipids in the digestive system.

PMID- 23175344
TI  - [Iron metabolism and maternal-fetal iron circulation].
AB  - Iron is an essential micronutrient for the proper functioning of most organisms.
      This element is used in oxygen transport, myelin and neurotransmitters synthesis,
      cell cycle and synthesis of nucleic acids. The importance of iron in the
      maturation of lymphocytes and proper functioning of the eye is also stressed.
      Newborns are particularly sensitive to imbalances in iron metabolism. Iron
      deficiency during pregnancy carries serious clinical consequences. It seems that
      a key role in the transport of iron between mother and fetus is plays by hepcidin
      and, described in 2010 zyklopen. The physiological role of proteins involved in
      iron metabolism and transport of this metal by the placenta are described in this
      paper. 

PMID- 23175345
TI  - ["Vicious circles" of glioblastoma tumors: vascularization and invasiveness].
AB  - Glioblastoma multiforme is the most common and a particularly aggressive form of
      glial primary brain tumors. This malignancy accounts for ca. 70% of all diagnosed
      cases. Unfortunately, average survival of glioma patients does not exceed one
      year from diagnosis. Specific vascularization pattern (presence of numerous
      microvessels and glomerular vessels) and exceptional invasiveness are
      characteristic features of glioblastoma tumors. Both of these features reflect
      complex underlying processes forming two vicious circles. Common to both of these
      circles is the state of tumor underoxygenation. Hypoxia that occurs in the
      vicinity of abnormal tumor blood vessels stimulates formation of novel
      microvessels and invasiveness of tumor cells. In their essence, both of the
      vicious circles are processes allowing tumor cells to adapt to an underoxygenated
      tumor milieu. These processes play an important role in tumor progression, which
      reflects a specific type of evolution of cancer cells. Late effects of this
      evolution include appearance of highly aggressive, chemo- and radiotherapy
      resistant neoplastic cells. Increased adaptation capabilities of such cancer
      cells have a negative influence on the therapeutic process. Effective therapeutic
      strategies should not be directed against single cancer cell markers; instead,
      they should be targeted so as to break both vicious cycles. Herein we discuss
      several such strategies. In our opinion, effective therapeutic approaches must
      include a combination of several agents that recognize and simultaneously break
      both vicious cycles, i.e. vascularization and invasiveness. Also, agents that
      decrease hypoxia in cancer cells, for example drugs inhibiting activity of HIF
      1alpha, might also prove therapeutically effective in such approaches. 

PMID- 23175346
TI  - [Morphogenesis, structure and properties of lymphatic vessels].
AB  - In this paper, we present literature results related to structure and various
      manners of lymphatic vessel formation during embryonic development and in
      pathological events, such as tumorigenesis, wound healing, and other diseases.
      The functions of the lymphatic system include the collection of fluids that enter
      tissues from the circulation, absorption of lipids and lipid-soluble vitamins
      from the intestine and their subsequent transport, participation in antigen,
      dendritic cell, and lymphocyte migration. The lymphatic system is also a route
      for tumor cell and inflammatory cell transport. Native lymphatic capillaries
      differ from blood capillaries by having an irregular lumen, a discontinuous
      basement membrane, absence of pericytes, and a strong anchorage of their
      endothelial cells to the extracellular matrix via microfibrils built of emilin
      and fibrillin. Lymphatic endothelial cells express surface antigens such as Lyve
      1, podoplanin, VEGFR3 (Flk4) and transcription factor Prox-1, as well as
      molecules which are common for blood endothelial cells and lymphatic endothelial
      cells (CD31, CD34, Flk-1, Tie-1, Tie-2, neuropilin 2). Lymphatic vessel formation
      during embryonic development starts with the occurrence of lymphatic sacs
      sprouting from systemic jugular veins and/or by co-option of lymphangioblasts or
      hematopoietic-derived cells. It can also proceed by dedifferentiation of venous
      endothelial cells after their detachment from the venous system, migration to the
      target places within the body and assembly in the lymphatic lumen. Mechanisms of
      lymphatic vessel formation during embryonic development and in pathological
      conditions, such as tumorigenesis, wound healing, and metastasis, is regulated by
      a plethora of growth factors and molecules, among which the most important are
      VEGF-C, VEGF-D, HGF, FGF, retinoic acid, IL-3, and IL-7. Macrophages and cells
      bearing CD45 phenotype seem to take part in the formation of lymphatics.
      Macrophages might act as a source of growth factors and/or as modulators playing
      a role in vessel caliber regulation during lymphangiogenesis. We discuss the most
      important diseases of the lymphatic system, their molecular basis and tumors
      derived from lymphatic vessels. 

PMID- 23175347
TI  - [HMGB1--its role in tumor progression and anticancer therapy].
AB  - HMGB1 is an evolutionarily conserved protein with a wide spectrum of action. Its
      main receptors are RAGE and TLR found on the surface of immune system cells as
      well as endothelial cells. Although signaling pathways for both receptor groups
      are different, ultimately they both activate NFkappaB transcription factor which,
      in turn, activates genes encoding adhesion proteins, proinflammatory cytokines
      and proangiogenic factors. Inside cells, HMGB1 is found mainly in the cell
      nucleus, where it participates in replication, recombination, transcription and
      DNA repair processes. Following release into the extracellular space, HMGB1
      becomes a proinflammatory cytokine which stimulates formation of new blood
      microvessels, enhances cell migration, activates the inflammatory condition and
      affects cell proliferation. HMGB1 protein also takes part in regeneration of
      damaged tissues and stimulates autophagy.    HMGB1 plays a potential role in
      anticancer therapy. Increased amounts of HMGB1 in cancer cells and elevated
      levels in the bloodstream are noted among patients afflicted with various
      cancers. HMGB1 protects cells from apoptosis, as it affects telomere stability.
      HMGB1 also stimulates a number of proteins involved in proliferation of cancer
      cells and inhibits signals that control cell growth. Ability to arrest HMGB1
      release from cells or to inhibit its activity appears to be a promising
      therapeutic approach. At present, several inhibitors of HMGB1 are known and can
      be used in anticancer therapy.   

PMID- 23175348
TI  - [Autophagy--molecular mechanism, apoptosis and cancer].
AB  - Autophagy is a catabolic process involving the degradation of long-lived proteins
      and organelles through the lysosomal machinery. In eukaryotic cells, among the
      three types of autophagy the most extensively studied is macroautophagy.
      Macroautophagy (hereafter referred to as autophagy) is characterized by
      sequestration of bulk cytoplasm in double-membrane vesicles, called
      autophagosomes, which ultimately fuse with lysosomes, resulting in degradation of
      their contents. Autophagy is responsible for the maintenance of intracellular
      homeostasis and enables cell survival under stress conditions. However, this
      process is also involved in the pathogenesis of diverse diseases, including
      cancers. In the cancer cell, autophagy plays a dual role, as a mechanism
      responsible for protecting or killing the cell. In most cases chemotherapy
      induced autophagy in tumor cells is a prosurvival response which potentially
      leads to development of drug resistance. However, autophagy can also lead to cell
      death, thus enhancing treatment efficacy. It is important for the anticancer
      therapy to find the type of cancer cells which are susceptible to autophagy and
      to determine whether the autophagy induced by the applied therapy leads to cells'
      death or their survival and subsequently to therapy resistance. In this review,
      the molecular mechanism of macroautophagy and the most important signaling
      transduction pathways involved in regulation of this process in cancer cells are
      presented. The dual function of autophagy in tumorigenesis and the implications
      of autophagy modulation for cancer therapy are also discussed.

PMID- 23175349
TI  - [A remedy against obesity? The role of lactoferrin in the metabolism of glucose
      and lipids].
AB  - Obesity, dyslipidemia, hyperglycemia/type II diabetes and hypertension together
      constitute the so-called metabolic syndrome. Frequency of occurrence of these
      serious metabolic disturbances is associated with life style and is on the rise
      in prosperous industrialized countries. These diseases represent not only a
      serious health problem but also social and economic ones, and involve in
      prophylaxis and treatment various specialists (physicians, dieticians and
      psychologists). For about two decades research has been conducted on the
      possibility to apply milk-derived proteins in prevention and treatment of the
      above mentioned metabolic diseases. Lactoferrin (LF), a protein present in milk
      and excretory fluids of mammals, is one of the most intensively studied milk
      proteins for therapeutic application. Initial trials revealing an advantageous
      effect of LF on lipid metabolism and obesity enrolled only a few volunteers and
      were performed in Japan in 2003. Subsequent trials were conducted on animals as
      well as in clinics, and the positive results were supported by in vitro tests.
      After oral administration of LF, decreases of body weight, waist measurement,
      visceral fat tissue, plasma and liver fatty acid concentrations, triglycerides
      and cholesterol were registered. The mechanism of LF action may involve several
      processes, such as inhibition of adipogenesis, decrease of dietary triglyceride
      absorption, elevation of HDL cholesterol possessing anti-atherogenic properties,
      inhibition of accumulation of oxidized LDL cholesterol forms in macrophages and
      protection against formation of foam cells. LF also increases the susceptibility
      of cells to insulin action, including in conditions when the response to insulin
      is lowered (during inflammation). In addition, LF regulates activity of insulin
      like growth factor (IGF). The data collected to date indicate that LF is a
      promising, completely nontoxic, natural remedy which (as for example a food
      supplement) may be applied in long-term prophylaxis and therapy of metabolic
      disturbances, such as dyslipidemia, obesity and insulin resistance/type II
      diabetes. 

PMID- 23175350
TI  - Polymorphism of CD36 gene, carbohydrate metabolism and plasma CD36 concentration
      in obese children. A preliminary study.
AB  - INTRODUCTION: CD36 may play an important role in removal of oxidized LDLs from
      plasma, protein glycation, the pathogenesis of insulin resistance, type 2
      diabetes, and diabetic micro- and macroangiopathy. Some reports have pointed to
      decreased expression of macrophages in association with mutations of the CD36
      gene in hyperglycemic and obese subjects. The aim of the study was to search for
      an association between CD36 gene polymorphism and carbohydrate metabolism
      disturbances or variability of plasma soluble CD36 concentrations in obese
      children. MATERIAL/METHODS: The study included 60 children aged 10 to 15 years:
      30 with (study group) and 30 without (control group) obesity. Each patient's
      glycated hemoglobin, weight, height, waist and hip circumference, and systolic
      and diastolic blood pressure were measured, BMI, WHR and MAP were calculated, and
      oral glucose tolerance test was performed with glucose and insulin concentration
      measurements. Amplicons of exons 4-6 of CD36 were studied using DHPLC technique.
      The PCR products with alterations were bidirectionally sequenced. Plasma
      concentrations of human antigen CD36 was measured using a commercially available
      enzyme-linked immunosorbent assay (ELISA). RESULTS: We found two intronic
      alterations: IVS3-6 T/C (rs3173798) and IVS4-10 G/A (rs3211892), one
      nonsynonymous substitution: G367A (Glu123Lys, rs183461468) in exon 5 and two
      synonymous transitions in exon 6: G573A (Pro191Pro, rs5956) and A591T (Thr197Thr,
      rs141680676). There were no significant differences in any biochemical or
      morphometric parameters between genotype groups. DISCUSSION: The polymorphisms of
      the studied fragment of CD36 are not associated with carbohydrate metabolism
      disturbances or the variability of plasma soluble CD36 concentrations in obese
      children, but further research is necessary to assess their functional
      implications.

PMID- 23175351
TI  - Probing self-assembled 1,3,5-benzenetrisamides in isotactic polypropylene by 13C
      DQ solid-state NMR spectroscopy.
AB  - Using (13)C double quantum solid-state NMR spectroscopy, we were able to observe
      nuclei of a supramolecular BTA based additive on the nanoscale in a matrix of i
      PP at a concentration of only 0.09 wt%. These nuclei exhibit the analogous
      structural features as the crystalline phase of the neat additive.

PMID- 23175352
TI  - Lime sulfur toxicity to broad mite, to its host plants and to natural enemies.
AB  - BACKGROUND: An acaricidal effect of lime sulfur has not been demonstrated for
      Polyphagotarsonemus latus. However, lime sulfur can cause toxicity to natural
      enemies and to host plants. In this study, the toxicity of different
      concentrations of lime sulfur to P. latus, to the predatory mite Amblyseius
      herbicolus and to the predatory insect Chrysoperla externa was evaluated.
      Additionally, the phytotoxicity of lime sulfur to two P. latus hosts, chili
      pepper and physic nut plants, was determined. RESULTS: Lime sulfur at a
      concentration of 9.5 mL L(-1) restrained P. latus population growth. However,
      this concentration was deleterious to natural enemies. The predatory mite A.
      herbicolus showed a negative value of instantaneous growth rate, and only 50% of
      the tested larvae of C. externa reached adulthood when exposed to 10 mL L(-1) .
      Physic nut had severe injury symptoms when sprayed with all tested lime sulfur
      concentrations. For chili pepper plants, no phytoxicity was observed at any
      tested concentration. CONCLUSION: Lime sulfur might be used for P. latus control
      on chili pepper but not on physic nut owing to phytotoxicity. Care should be
      taken when using lime sulfur in view of negative effects on natural enemies.
      Selective lime sulfur concentration integrated with other management tactics may
      provide an effective and sustainable P. latus control on chili pepper.

PMID- 23175353
TI  - Adult sea lamprey tolerates biliary atresia by altering bile salt composition and
      renal excretion.
AB  - The sea lamprey (Petromyzon marinus) is a genetically programmed animal model for
      biliary atresia, as it loses its bile ducts and gallbladder during metamorphosis.
      However, in contrast to patients with biliary atresia or other forms of
      cholestasis who develop progressive disease, the postmetamorphosis lampreys grow
      normally to adult size. To understand how the adult lamprey thrives without the
      ability to secrete bile, we examined bile salt homeostasis in larval and adult
      lampreys. Adult livers were severely cholestatic, with levels of bile salts >1
      mM, but no evidence of necrosis, fibrosis, or inflammation. Interestingly, both
      larvae and adults had normal plasma levels (~10 MUM) of bile salts. In larvae,
      petromyzonol sulfate (PZS) was the predominant bile salt, whereas the major bile
      salts in adult liver were sulfated C27 bile alcohols. Cytotoxicity assays
      revealed that PZS was highly toxic. Pharmacokinetic studies in free-swimming
      adults revealed that ~35% of intravenously injected bromosulfophthalein (BSP) was
      eliminated over a 72-hour period. Collection of urine and feces demonstrated that
      both endogenous and exogenous organic anions, including biliverdin, bile salts,
      and BSP, were predominantly excreted by way of the kidney, with minor amounts
      also detected in feces. Gene expression analysis detected marked up-regulation of
      orthologs of known organic anion and bile salt transporters in the kidney, with
      lesser effects in the intestine and gills in adults compared to larvae. These
      findings indicate that adult lampreys tolerate cholestasis by altering hepatic
      bile salt composition, while maintaining normal plasma bile salt levels
      predominantly through renal excretion of bile products. Therefore, we conclude
      that strategies to accelerate renal excretion of bile salt and other toxins
      should be beneficial for patients with cholestasis. (HEPATOLOGY 2013;57:2418
      2426).

PMID- 23175354
TI  - Comparison of the pathologic and pathogenic features in six different regions of
      postmortem brains of three patients with fatal familial insomnia.
AB  - Fatal familial insomnia (FFI) is an autosomal dominant prion disease clinically
      characterized by rapidly progressive insomnia, prominent autonomic alterations
      and behavioral disturbance. The D178N mutation of the prion protein gene (PRNP)
      on chromosome 20 in conjunction with methionine at codon 129 is a molecular
      feature. Although the neuropathological characteristics of FFI are well
      documented, the neuropathologic and pathogenic features of FFI patients remain
      poorly understood. Six brain regions of postmortem brains from 3 FFI patients
      were examined using immunohistochemistry, western blot analyses and quantitative
      real-time PCR. In all 3 brain specimens, reactive astrogliosis was found to be
      more severe in the thalamus than in the cortex regions. Western blot analyses
      showed that all three brains expressed PrP, but only 2 were associated with
      significantly weak proteinase K (PK) resistance. However, the conformational
      stabilities of PrPSc in the 3 FFI brains were significantly weaker than those
      presented in a G114V genetic Creutzfeldt-Jakob disease (gCJD) case.
      Immunohistochemistry and western blot analyses showed comparable amounts of
      neuron-specific enolase (NSE)-positive stained cells and NSE protein among the
      different regions in the three brains. In addition, the transcriptional levels of
      glial fibrillary acidic protein (GFAP) and NSE-specific mRNAs were coincident
      with the expression of these proteins. In conclusion, in the present study, we
      described the detailed regional neuropathology of FFI cases.

PMID- 23175355
TI  - Comparative analysis of simian immunodeficiency virus gag-specific effector and
      memory CD8+ T cells induced by different adenovirus vectors.
AB  - Adenovirus (Ad) vectors are widely used as experimental vaccines against several
      infectious diseases, but the magnitude, phenotype, and functionality of CD8(+) T
      cell responses induced by different adenovirus serotypes have not been compared.
      To address this question, we have analyzed simian immunodeficiency virus Gag
      specific CD8(+) T cell responses in mice following vaccination with Ad5, Ad26,
      and Ad35. Our results show that although Ad5 is more immunogenic than Ad26 and
      Ad35, the phenotype, function, and recall potential of memory CD8(+) T cells
      elicited by these vectors are substantially different. Ad26 and Ad35 vectors
      generated CD8(+) T cells that display the phenotype and function of long-lived
      memory T cells, whereas Ad5 vector-elicited CD8(+) T cells are of a more
      terminally differentiated phenotype. In addition, hepatic memory CD8(+) T cells
      elicited by Ad26 and Ad35 mounted more robust recall proliferation following
      secondary challenge than those induced by Ad5. Furthermore, the boosting
      potential was higher following priming with alternative-serotype Ad vectors than
      with Ad5 vectors in heterologous prime-boost regimens. Anamnestic CD8(+) T cell
      responses were further enhanced when the duration between priming and boosting
      was extended from 30 to 60 days. Our results demonstrate that heterologous prime
      boost vaccine regimens with alternative-serotype Ad vectors elicited more
      functional memory CD8(+) T cells than any of the regimens containing Ad5. In
      summary, these results suggest that alternative-serotype Ad vectors will prove
      useful as candidates for vaccine development against human immunodeficiency virus
      type 1 and other pathogens and also emphasize the importance of a longer rest
      period between prime and boost for generating optimal CD8(+) T cell immunity.

PMID- 23175356
TI  - Disulfide bonds in hepatitis C virus glycoprotein E1 control the assembly and
      entry functions of E2 glycoprotein.
AB  - Class II membrane fusion proteins have been described in viruses in which the
      envelope proteins are derived from a precursor polyprotein containing two
      transmembrane glycoproteins arranged in tandem. Although the second protein,
      which carries the membrane fusion function, is in general well characterized, the
      companion protein, which is a protein chaperone for the folding of the fusion
      protein, is less well characterized for some viruses, like hepatitis C virus
      (HCV). To investigate the role of the class II companion glycoprotein E1 of HCV,
      we chose to target conserved cysteine residues in the protein, and we
      systematically mutated them in a full-length infectious HCV clone by reverse
      genetics. All the mutants were infectious, albeit with lower titers than the wild
      type virus. The reduced infectivity was in part due to a decrease in viral
      assembly, as revealed by measurement of intracellular infectivity and by
      quantification of core protein released from cells transfected with mutant
      genomes. Analyses of mutated proteins did not show any major defect in folding.
      However, the mutations reduced virus stability, and they could also affect the
      density of infectious viral particles. Mutant viruses also showed a defect in
      cell-to-cell transmission. Finally, our data indicate that HCV glycoprotein E1
      can also affect the fusion protein E2 by modulating its recognition by the
      cellular coreceptor CD81. Therefore, in the context of HCV, our data identify an
      additional function of a class II companion protein as a molecule that can
      control the binding capacity of the fusion protein.

PMID- 23175357
TI  - Antigenicity and immunogenicity of RV144 vaccine AIDSVAX clade E envelope
      immunogen is enhanced by a gp120 N-terminal deletion.
AB  - An immune correlates analysis of the RV144 HIV-1 vaccine trial revealed that
      antibody responses to the gp120 V1/V2 region correlated inversely with infection
      risk. The RV144 protein immunogens (A244-rp120 and MN-rgp120) were modified by an
      N-terminal 11-amino-acid deletion (Delta11) and addition of a herpes simplex
      virus (HSV) gD protein-derived tag (gD). We investigated the effects of these
      modifications on gp120 expression, antigenicity, and immunogenicity by comparing
      unmodified A244 gp120 with both Delta11 deletion and gD tag and with Delta11
      only. Analysis of A244 gp120, with or without Delta11 or gD, demonstrated that
      the Delta11 deletion, without the addition of gD, was sufficient for enhanced
      antigenicity to gp120 C1 region, conformational V2, and V1/V2 gp120
      conformational epitopes. RV144 vaccinee serum IgGs bound more avidly to A244
      gp120 Delta11 than to the unmodified gp120, and their binding was blocked by C1,
      V2, and V1/V2 antibodies. Rhesus macaques immunized with the three different
      forms of A244 gp120 proteins gave similar levels of gp120 antibody titers,
      although higher antibody titers developed earlier in A244 Delta11 gp120-immunized
      animals. Conformational V1/V2 monoclonal antibodies (MAbs) gave significantly
      higher levels of blocking of plasma IgG from A244 Delta11 gp120-immunized animals
      than IgG from animals immunized with unmodified A244 gp120, thus indicating a
      qualitative difference in the V1/V2 antibodies induced by A244 Delta11 gp120.
      These results demonstrate that deletion of N-terminal residues in the RV144 A244
      gp120 immunogen improves both envelope antigenicity and immunogenicity.

PMID- 23175358
TI  - Nuclear export signal-interacting protein forms complexes with lamin A/C-Nups to
      mediate the CRM1-independent nuclear export of large hepatitis delta antigen.
AB  - Nuclear export is an important process that not only regulates the functions of
      cellular factors but also facilitates the assembly of viral nucleoprotein
      complexes. Chromosome region maintenance 1 (CRM1) that mediates the transport of
      proteins bearing the classical leucine-rich nuclear export signal (NES) is the
      best-characterized nuclear export receptor. Recently, several CRM1-independent
      nuclear export pathways were also identified. The nuclear export of the large
      form of hepatitis delta antigen (HDAg-L), a nucleocapsid protein of hepatitis
      delta virus (HDV), which contains a CRM1-independent proline-rich NES, is
      mediated by the host NES-interacting protein (NESI). The mechanism of the NESI
      protein in mediating nuclear export is still unknown. In this study, NESI was
      characterized as a highly glycosylated membrane protein. It interacted and
      colocalized well in the nuclear envelope with lamin A/C and nucleoporins.
      Importantly, HDAg-L could be coimmunoprecipitated with lamin A/C and
      nucleoporins. In addition, binding of the cargo HDAg-L to the C terminus of NESI
      was detected for the wild-type protein but not for the nuclear export-defective
      HDAg-L carrying a P205A mutation [HDAg-L(P205A)]. Knockdown of lamin A/C
      effectively reduced the nuclear export of HDAg-L and the assembly of HDV. These
      data indicate that by forming complexes with lamin A/C and nucleoporins, NESI
      facilitates the CRM1-independent nuclear export of HDAg-L.

PMID- 23175359
TI  - Screening and rational design of hepatitis C virus entry inhibitory peptides
      derived from GB virus A NS5A.
AB  - Chronic infection by hepatitis C virus (HCV) is a cause of the global burden of
      liver diseases. HCV entry into hepatocytes is a complicated and multistep process
      that represents a promising target for antiviral intervention. The recently
      reported amphipathic alpha-helical virucidal peptide (C5A) from the HCV NS5A
      protein suggests a new category of antiviral drug candidates. In this study, to
      identify C5A-like HCV inhibitors, synthetic peptides derived from the C5A
      corresponding NS5 protein region of selected Flaviviridae viruses were evaluated
      for their anti-HCV activities. A peptide from GB virus A (GBV-A), but not other
      flaviviruses, demonstrated an inhibitory effect on HCV infection. Through a
      series of sequence optimizations and modifications of the peptide helicity and
      hydrophobicity, we obtained a peptide designated GBVA10-9 with highly potent anti
      HCV activity. GBVA10-9 suppressed infection with both cell culture-derived and
      pseudotyped HCV in vitro, and the 50% cell culture inhibitory concentration
      ranged from 20 nM to 160 nM, depending on the genotypic origin of the envelope
      proteins. GBVA10-9 had no detectable effects on either HCV attachment to Huh7.5.1
      cells or viral RNA replication. No virucidal activity was found with GBVA10-9,
      suggesting an action mechanism distinct from that of C5A. The inhibitory effect
      of GBVA10-9 appeared to occur at the postbinding step during viral entry. Taken
      together, the results with GBVA10-9 demonstrated a potent activity for blocking
      HCV entry that might be used in combination with other antivirals directly
      targeting virus-encoded enzymes. Furthermore, GBVA10-9 also provides a novel tool
      to dissect the detailed mechanisms of HCV entry.

PMID- 23175360
TI  - High-risk human papillomavirus E6 oncoproteins interact with 14-3-3zeta in a PDZ
      binding motif-dependent manner.
AB  - Cervical cancer develops through the combined activities of the human
      papillomavirus (HPV) E6 and E7 oncoproteins. A defining characteristic of E6
      oncoproteins derived from cancer-causing HPV types is the presence of a PDZ
      binding motif (PBM) at the extreme carboxy terminus of the protein which is
      absent from E6 proteins derived from the so-called low-risk HPV types. Within
      this PBM is also a protein kinase A (PKA) phospho-acceptor site, which is thought
      to negatively regulate the association of E6 with its PDZ domain-containing
      substrates. We can now show that phosphorylation of E6 by PKA and/or AKT confers
      the ability to interact with 14-3-3zeta. The interaction is direct and specific
      for the high-risk HPV E6 oncoproteins, although there are significant differences
      in the efficiencies with which HPV-16, HPV-18, and HPV-31 E6 oncoproteins can
      associate with 14-3-3zeta; this correlates directly with their respective
      susceptibilities to phosphorylation by PKA and/or AKT. We demonstrate here that
      the interaction between E6 and 14-3-3zeta also requires integrity of the E6 PBM,
      and downregulation of 14-3-3zeta results in a marked reduction in the levels of
      HPV-18 E6 expression in HeLa cells. Using phospho-specific anti-E6 antibodies, we
      also demonstrate significant levels of E6 phosphorylation in vivo. These studies
      redefine the potential relevance of the E6 PBM in the development of cervical
      cancer, suggesting that interaction with 14-3-3zeta, as well as the more well
      established interactions with PDZ domain-containing substrates, is likely to be
      responsible for the biological activities attributed to this region of the high
      risk HPV E6 oncoproteins.

PMID- 23175361
TI  - Amino acid exchanges in the putative nuclear export signal of adenovirus type 5
      L4-100K severely reduce viral progeny due to effects on hexon biogenesis.
AB  - The adenovirus type 5 nonstructural L4-100K protein is indispensable for
      efficient lytic infection. During the late phase, L4-100K promotes selective
      translation of viral late transcripts and mediates the trimerization of the major
      capsid protein hexon. In the present study, the role of a potential nuclear
      export signal in L4-100K was investigated. Intriguingly, amino acid substitutions
      in this sequence resulted in severely diminished progeny virus production,
      seemingly by precluding proper hexon biogenesis.

PMID- 23175362
TI  - A Sendai virus-derived RNA agonist of RIG-I as a virus vaccine adjuvant.
AB  - The innate immune system is responsible for recognizing invading pathogens and
      initiating a protective response. In particular, the retinoic acid-inducible gene
      1 protein (RIG-I) participates in the recognition of single- and double-stranded
      RNA viruses. RIG-I activation leads to the production of an appropriate cytokine
      and chemokine cocktail that stimulates an antiviral state and drives the adaptive
      immune system toward an efficient and specific response against the ongoing
      infection. One of the best-characterized natural RIG-I agonists is the defective
      interfering (DI) RNA produced by Sendai virus strain Cantell. This 546-nucleotide
      RNA is a well-known activator of the innate immune system and an extremely potent
      inducer of type I interferon. We designed an in vitro-transcribed RNA that
      retains the type I interferon stimulatory properties, and the RIG-I affinity of
      the Sendai virus produced DI RNA both in vitro and in vivo. This in vitro
      synthesized RNA is capable of enhancing the production of anti-influenza virus
      hemagglutinin (HA)-specific IgG after intramuscular or intranasal
      coadministration with inactivated H1N1 2009 pandemic vaccine. Furthermore, our
      adjuvant is equally effective at increasing the efficiency of an influenza
      A/Puerto Rico/8/34 virus inactivated vaccine as a poly(I.C)- or a squalene-based
      adjuvant. Our in vitro-transcribed DI RNA represents an excellent tool for the
      study of RIG-I agonists as vaccine adjuvants and a starting point in the
      development of such a vaccine.

PMID- 23175363
TI  - Inhibition of cellular autophagy deranges dengue virion maturation.
AB  - Autophagy is an important component of the innate immune response, directly
      destroying many intracellular pathogens. However, some pathogens, including
      several RNA viruses, subvert the autophagy pathway, or components of the pathway,
      to facilitate their replication. In the present study, the effect of inhibiting
      autophagy on the growth of dengue virus was tested using a novel inhibitor,
      spautin-1 (specific and potent autophagy inhibitor 1). Inhibition of autophagy by
      spautin-1 generated heat-sensitive, noninfectious dengue virus particles,
      revealing a large effect of components of the autophagy pathway on viral
      maturation. A smaller effect on viral RNA accumulation was also observed.
      Conversely, stimulation of autophagy resulted in increased viral titers and
      pathogenicity in the mouse. We conclude that the presence of functional autophagy
      components facilitates viral RNA replication and, more importantly, is required
      for infectious dengue virus production. Pharmacological inhibition of host
      processes is an attractive antiviral strategy to avoid selection of treatment
      resistant variants, and inhibitors of autophagy may prove to be valuable
      therapeutics against dengue virus infection and pathogenesis.

PMID- 23175364
TI  - Subcellular localization and function of an epitope-tagged p7 viroporin in
      hepatitis C virus-producing cells.
AB  - The hepatitis C virus (HCV) viroporin p7 is crucial for production of infectious
      viral progeny. However, its role in the viral replication cycle remains
      incompletely understood, in part due to the poor availability of p7-specific
      antibodies. To circumvent this obstacle, we inserted two consecutive
      hemagglutinin (HA) epitope tags at its N terminus. HA-tagged p7 reduced peak
      virus titers ca. 10-fold and decreased kinetics of virus production compared to
      the wild-type virus. However, HA-tagged p7 rescued virus production of a mutant
      virus lacking p7, thus providing formal proof that the tag does not disrupt p7
      function. In HCV-producing cells, p7 displayed a reticular staining pattern which
      colocalized with the HCV envelope glycoprotein 2 (E2) but also partially with
      viral nonstructural proteins 2, 3, and 5A. Using coimmunoprecipitation, we
      confirmed a specific interaction between p7 and NS2, whereas we did not detect a
      stable interaction with core, E2, or NS5A. Moreover, we did not observe p7
      incorporation into affinity-purified virus particles. Consistently, there was no
      evidence supporting a role of p7 in viral entry, as an anti-HA antibody was not
      able to neutralize Jc1 virus produced from an HA-p7-tagged genome. Collectively,
      these findings highlight a stable interaction between p7 and NS2 which is likely
      crucial for production of infectious HCV particles. Use of this functional
      epitope-tagged p7 variant should facilitate the analysis of the final steps of
      the HCV replication cycle.

PMID- 23175365
TI  - A new rabies vaccine based on a recombinant ORF virus (parapoxvirus) expressing
      the rabies virus glycoprotein.
AB  - The present study describes the generation of a new Orf virus (ORFV) recombinant,
      D1701-V-RabG, expressing the rabies virus (RABV) glycoprotein that is correctly
      presented on the surface of infected cells without the need of replication or
      production of infectious recombinant virus. One single immunization with
      recombinant ORFV can stimulate high RABV-specific virus-neutralizing antibody
      (VNA) titers in mice, cats, and dogs, representing all nonpermissive hosts for
      the ORFV vector. The protective immune response against severe lethal challenge
      infection was analyzed in detail in mice using different dosages, numbers, and
      routes for immunization with the ORFV recombinant. Long-term levels of VNA could
      be elicited that remained greater than 0.5 IU per ml serum, indicative for the
      protective status. Single applications of higher doses (10(7) PFU) can be
      sufficient to confer complete protection against intracranial (i.c.) challenge,
      whereas booster immunization was needed for protection by the application of
      lower dosages. Anamnestic immune responses were achieved by each of the seven
      tested routes of inoculation, including oral application. Finally, in vivo
      antibody-mediated depletion of CD4-positive and/or CD8-posititve T cell
      subpopulations during immunization and/or challenge infection attested the
      importance of CD4 T cells for the induction of protective immunity by D1701-V
      RabG. This report demonstrates another example of the potential of the ORFV
      vector and also indicates the capability of the new recombinant for vaccination
      of animals.

PMID- 23175366
TI  - Cleavage of interferon regulatory factor 7 by enterovirus 71 3C suppresses
      cellular responses.
AB  - Enterovirus 71 (EV71) is a positive-stranded RNA virus which is capable of
      inhibiting innate immunity. Among virus-encoded proteins, the 3C protein
      compromises the type I interferon (IFN-I) response mediated by retinoid acid
      inducible gene-I (RIG-I) or Toll-like receptor 3 that activates interferon
      regulatory 3 (IRF3) and IRF7. In the present study, we report that enterovirus 71
      downregulates IRF7 through the 3C protein, which inhibits the function of IRF7.
      When expressed in mammalian cells, the 3C protein mediates cleavage of IRF7
      rather than that of IRF3. This process is insensitive to inhibitors of caspase,
      proteasome, lysosome, and autophagy. H40D substitution in the 3C active site
      abolishes its activity, whereas R84Q or V154S substitution in the RNA binding
      motif has no effect. Furthermore, 3C-mediated cleavage occurs at the Q189-S190
      junction within the constitutive activation domain of IRF7, resulting in two
      cleaved IRF7 fragments that are incapable of activating IFN expression. Ectopic
      expression of wild-type IRF7 limits EV71 replication. On the other hand,
      expression of the amino-terminal domain of IRF7 enhances EV71 infection, which
      correlates with its ability to interact with and inhibit IRF3. These results
      suggest that control of IRF7 by the 3C protein may represent a viral mechanism to
      escape cellular responses.

PMID- 23175367
TI  - The spike protein VP4 defines the endocytic pathway used by rotavirus to enter
      MA104 cells.
AB  - Rotaviruses are internalized into MA104 cells by endocytosis, with different
      endocytic pathways used depending on the virus strain. The bovine rotavirus UK
      strain enters cells through a clathrin-mediated endocytic process, while the
      simian rhesus rotavirus (RRV) strain uses a poorly defined endocytic pathway that
      is clathrin and caveolin independent. The viral surface protein VP7 and the spike
      protein VP4 interact with cellular receptors during cell binding and penetration.
      To determine the viral protein that defines the mechanism of internalization, we
      used a panel of UK * RRV reassortant viruses having different combinations of the
      viral structural proteins. Characterization of the infectivities of these
      reassortants in MA104 cells either transfected with a small interfering RNA
      (siRNA) against the heavy chain of clathrin or incubated with hypertonic medium
      that destabilizes the clathrin coat clearly showed that VP4 determines the
      pathway of virus entry. Of interest, the characterization of Nar3, a sialic acid
      independent variant of RRV, showed that a single amino acid change in VP4 shifts
      the route of entry from being clathrin dependent to clathrin independent.
      Furthermore, characterizations of several additional rotavirus strains that
      differ in their use of cellular receptors showed that all entered cells by
      clathrin-mediated endocytosis, suggesting that diverse VP4-cell surface
      interactions can lead to rotavirus cell entry through this endocytic pathway.

PMID- 23175368
TI  - Dicer-2- and Piwi-mediated RNA interference in Rift Valley fever virus-infected
      mosquito cells.
AB  - Rift Valley fever virus (RVFV) is a Phlebovirus (Bunyaviridae family) transmitted
      by mosquitoes. It infects humans and ruminants, causing dramatic epidemics and
      epizootics in Africa, Yemen, and Saudi Arabia. While recent studies demonstrated
      the importance of the nonstructural protein NSs as a major component of virulence
      in vertebrates, little is known about infection of mosquito vectors. Here we
      studied RVFV infection in three different mosquito cell lines, Aag2 cells from
      Aedes aegypti and U4.4 and C6/36 cells from Aedes albopictus. In contrast with
      mammalian cells, where NSs forms nuclear filaments, U4.4 and Aag2 cells
      downregulated NSs expression such that NSs filaments were never formed in nuclei
      of U4.4 cells and disappeared at an early time postinfection in the case of Aag2
      cells. On the contrary, in C6/36 cells, NSs nuclear filaments were visible during
      the entire time course of infection. Analysis of virus-derived small interfering
      RNAs (viRNAs) by deep sequencing indicated that production of viRNAs was very low
      in C6/36 cells, which are known to be Dicer-2 deficient but expressed some viRNAs
      presenting a Piwi signature. In contrast, Aag2 and U4.4 cells produced large
      amounts of viRNAs predominantly matching the S segment and displaying Dicer-2 and
      Piwi signatures. Whereas 21-nucleotide (nt) Dicer-2 viRNAs were prominent during
      early infection, the population of 24- to 27-nt Piwi RNAs (piRNAs) increased
      progressively and became predominant later during the acute infection and during
      persistence. In Aag2 and U4.4 cells, the combined actions of the Dicer-2 and Piwi
      pathways triggered an efficient antiviral response permitting, among other
      actions, suppression of NSs filament formation and allowing establishment of
      persistence. In C6/36 cells, Piwi-mediated RNA interference (RNAi) appeared to be
      sufficient to mount an antiviral response against a secondary infection with a
      superinfecting virus. This study provides new insights into the role of Dicer and
      Piwi in mosquito antiviral defense and the development of the antiviral response
      in mosquitoes.

PMID- 23175369
TI  - Proteolytic processing of the human immunodeficiency virus envelope glycoprotein
      precursor decreases conformational flexibility.
AB  - The mature envelope glycoprotein (Env) spike on the surface of human
      immunodeficiency virus type 1 (HIV-1) virions is derived by proteolytic cleavage
      of a trimeric gp160 glycoprotein precursor. Remarkably, proteolytic processing of
      the HIV-1 Env precursor results in changes in Env antigenicity that resemble
      those associated with glutaraldehyde fixation. Apparently, proteolytic processing
      of the HIV-1 Env precursor decreases conformational flexibility of the Env
      trimeric complex, differentially affecting the integrity/accessibility of
      epitopes for neutralizing and nonneutralizing antibodies.

PMID- 23175370
TI  - Aerosol transmission of chronic wasting disease in white-tailed deer.
AB  - While the facile transmission of chronic wasting disease (CWD) remains
      incompletely elucidated, studies in rodents suggest that exposure of the
      respiratory mucosa may be an efficient pathway. The present study was designed to
      address this question in the native cervid host. Here, we demonstrate aerosol
      transmission of CWD to deer with a prion dose >20-fold lower than that used in
      previous oral inoculations. Inhalation of prions may facilitate transmission of
      CWD and, perhaps, other prion infections.

PMID- 23175371
TI  - The cellular autophagy pathway modulates human T-cell leukemia virus type 1
      replication.
AB  - Autophagy, a general homeostatic process for degradation of cytosolic proteins or
      organelles, has been reported to modulate the replication of many viruses. The
      role of autophagy in human T-cell leukemia virus type 1 (HTLV-1) replication has,
      however, been uncharacterized. Here, we report that HTLV-1 infection increases
      the accumulation of autophagosomes and that this accumulation increases HTLV-1
      production. We found that the HTLV-1 Tax protein increases cellular autophagosome
      accumulation by acting to block the fusion of autophagosomes to lysosomes,
      preventing the degradation of the former by the latter. Interestingly, the
      inhibition of cellular autophagosome-lysosome fusion using bafilomycin A
      increased the stability of the Tax protein, suggesting that cellular degradation
      of Tax occurs in part through autophagy. Our current findings indicate that by
      interrupting the cell's autophagic process, Tax exerts a positive feedback on its
      own stability.

PMID- 23175372
TI  - Differential requirements for HIV-1 Vif-mediated APOBEC3G degradation and RUNX1
      mediated transcription by core binding factor beta.
AB  - Core binding factor beta (CBFbeta), a transcription regulator through RUNX
      binding, was recently reported critical for Vif function. Here, we mapped the
      primary functional domain important for Vif function to amino acids 15 to 126 of
      CBFbeta. We also revealed that different lengths and regions are required for
      CBFbeta to assist Vif or RUNX. The important interaction domains that are
      uniquely required for Vif but not RUNX function represent novel targets for the
      development of HIV inhibitors.

PMID- 23175373
TI  - Low-resolution structure of vaccinia virus DNA replication machinery.
AB  - Smallpox caused by the poxvirus variola virus is a highly lethal disease that
      marked human history and was eradicated in 1979 thanks to a worldwide mass
      vaccination campaign. This virus remains a significant threat for public health
      due to its potential use as a bioterrorism agent and requires further development
      of antiviral drugs. The viral genome replication machinery appears to be an ideal
      target, although very little is known about its structure. Vaccinia virus is the
      prototypic virus of the Orthopoxvirus genus and shares more than 97% amino acid
      sequence identity with variola virus. Here we studied four essential viral
      proteins of the replication machinery: the DNA polymerase E9, the processivity
      factor A20, the uracil-DNA glycosylase D4, and the helicase-primase D5. We
      present the recombinant expression and biochemical and biophysical
      characterizations of these proteins and the complexes they form. We show that the
      A20D4 polymerase cofactor binds to E9 with high affinity, leading to the
      formation of the A20D4E9 holoenzyme. Small-angle X-ray scattering yielded
      envelopes for E9, A20D4, and A20D4E9. They showed the elongated shape of the
      A20D4 cofactor, leading to a 150-A separation between the polymerase active site
      of E9 and the DNA-binding site of D4. Electron microscopy showed a 6-fold
      rotational symmetry of the helicase-primase D5, as observed for other SF3
      helicases. These results favor a rolling-circle mechanism of vaccinia virus
      genome replication similar to the one suggested for tailed bacteriophages.

PMID- 23175374
TI  - Antibodies with high avidity to the gp120 envelope protein in protection from
      simian immunodeficiency virus SIV(mac251) acquisition in an immunization regimen
      that mimics the RV-144 Thai trial.
AB  - The recombinant canarypox vector, ALVAC-HIV, together with human immunodeficiency
      virus (HIV) gp120 envelope glycoprotein, has protected 31.2% of Thai individuals
      from HIV acquisition in the RV144 HIV vaccine trial. This outcome was unexpected,
      given the limited ability of the vaccine components to induce CD8(+) T-cell
      responses or broadly neutralizing antibodies. We vaccinated macaques with an
      immunization regimen intended to mimic the RV144 trial and exposed them
      intrarectally to a dose of the simian immunodeficiency virus SIV(mac251) that
      transmits few virus variants, similar to HIV transmission to humans. Vaccination
      induced anti-envelope antibodies in all vaccinees and CD4(+) and CD8(+) T-cell
      responses. Three of the 11 macaques vaccinated with ALVAC-SIV/gp120 were
      protected from SIV(mac251) acquisition, but the result was not significant. The
      remaining vaccinees were infected and progressed to disease. The magnitudes of
      vaccine-induced SIV(mac251)-specific T-cell responses and binding antibodies were
      not significantly different between protected and infected animals. However, sera
      from protected animals had higher avidity antibodies to gp120, recognized the
      variable envelope regions V1/V2, and reduced SIV(mac251) infectivity in cells
      that express high levels of alpha(4)beta(7) integrins, suggesting a functional
      role of antibodies to V2. The current results emphasize the utility of
      determining the titer of repeated mucosal challenge in the preclinical evaluation
      of HIV vaccines.

PMID- 23175375
TI  - Reactive oxygen species are induced by Kaposi's sarcoma-associated herpesvirus
      early during primary infection of endothelial cells to promote virus entry.
AB  - The entry of Kaposi's sarcoma-associated herpesvirus (KSHV) into human dermal
      microvascular endothelial cells (HMVEC-d), natural in vivo target cells, via
      macropinocytosis is initiated through a multistep process involving the binding
      of KSHV envelope glycoproteins with cell surface alpha3beta1, alphaVbeta3, and
      alphaVbeta5 integrin molecules and tyrosine kinase ephrin-A2 receptor, followed
      by the activation of preexisting integrin-associated signaling molecules such as
      focal adhesion kinase (FAK), Src, c-Cbl, phosphoinositide 3-kinase (PI-3K), and
      Rho-GTPases. Many viruses, including KSHV, utilize cellular reactive oxygen
      species (ROS) for viral genomic replication and survival within host cells;
      however, the role of ROS in early events of viral entry and the induction of
      signaling has not been elucidated. Here we show that KSHV induced ROS production
      very early during the infection of HMVEC-d cells and that ROS production was
      sustained over the observation period (24 h postinfection). ROS induction was
      dependent on the binding of KSHV to the target cells, since pretreatment of the
      virus with heparin abolished ROS induction. Pretreatment of HMVEC-d cells with
      the antioxidant N-acetylcysteine (NAC) significantly inhibited KSHV entry, and
      consequently gene expression, without affecting virus binding. In contrast,
      H(2)O(2) treatment increased the levels of KSHV entry and infection. In addition,
      NAC inhibited KSHV infection-induced translocation of alphaVbeta3 integrin into
      lipid rafts, actin-dependent membrane perturbations, such as blebs, observed
      during macropinocytosis, and activation of the signal molecules ephrin-A2
      receptor, FAK, Src, and Rac1. In contrast, H(2)O(2) treatment increased the
      activation of ephrin-A2, FAK, Src, and Rac1. These studies demonstrate that KSHV
      infection induces ROS very early during infection to amplify the signaling
      pathways necessary for its efficient entry into HMVEC-d cells via
      macropinocytosis.

PMID- 23175376
TI  - Ribavirin-resistant mutants of human enterovirus 71 express a high replication
      fidelity phenotype during growth in cell culture.
AB  - It has been shown in animal models that ribavirin-resistant poliovirus with a
      G64S mutation in its 3D polymerase has high replication fidelity coupled with
      attenuated virulence. Here, we describe the effects of mutagenesis in the human
      enterovirus 71 (HEV71) 3D polymerase on ribavirin resistance and replication
      fidelity. Seven substitutions were introduced at amino acid position 3D-G64 of a
      HEV71 full-length infectious cDNA clone (26M). Viable clone-derived virus
      populations were rescued from the G64N, G64R, and G64T mutant cDNA clones. The
      clone-derived G64R and G64T mutant virus populations were resistant to growth
      inhibition in the presence of 1,600 MUM ribavirin, whereas the growth of parental
      26M and the G64N mutant viruses were inhibited in the presence of 800 MUM
      ribavirin. Nucleotide sequencing of the 2C and 3D coding regions revealed that
      the rate of random mutagenesis after 13 passages in the presence of 400 MUM
      ribavirin was nearly 10 times higher in the 26M genome than in the mutant G64R
      virus genome. Furthermore, random mutations acquired in the 2C coding regions of
      26M and G64N conferred resistance to growth inhibition in the presence of 0.5 mM
      guanidine, whereas the G64R and G64T mutant virus populations remained
      susceptible to growth inhibition by 0.5 mM guanidine. Interestingly, a S264L
      mutation identified in the 3D coding region of 26M after ribavirin selection was
      also associated with both ribavirin-resistant and high replication fidelity
      phenotypes. These findings are consistent with the hypothesis that the 3D-G64R,
      3D-G64T, and 3D-S264L mutations confer resistance upon HEV71 to the antiviral
      mutagen ribavirin, coupled with a high replication fidelity phenotype during
      growth in cell culture.

PMID- 23175377
TI  - The human cytomegalovirus UL51 protein is essential for viral genome cleavage
      packaging and interacts with the terminase subunits pUL56 and pUL89.
AB  - Cleavage of human cytomegalovirus (HCMV) genomes as well as their packaging into
      capsids is an enzymatic process mediated by viral proteins and therefore a
      promising target for antiviral therapy. The HCMV proteins pUL56 and pUL89 form
      the terminase and play a central role in cleavage-packaging, but several
      additional viral proteins, including pUL51, had been suggested to contribute to
      this process, although they remain largely uncharacterized. To study the function
      of pUL51 in infected cells, we constructed HCMV mutants encoding epitope-tagged
      versions of pUL51 and used a conditionally replicating virus (HCMV-UL51-ddFKBP),
      in which pUL51 levels could be regulated by a synthetic ligand. In cells infected
      with HCMV-UL51-ddFKBP, viral DNA replication was not affected when pUL51 was
      knocked down. However, no unit-length genomes and no DNA-filled C capsids were
      found, indicating that cleavage of concatemeric HCMV DNA and genome packaging
      into capsids did not occur in the absence of pUL51. pUL51 was expressed mainly
      with late kinetics and was targeted to nuclear replication compartments, where it
      colocalized with pUL56 and pUL89. Upon pUL51 knockdown, pUL56 and pUL89 were no
      longer detectable in replication compartments, suggesting that pUL51 is needed
      for their correct subnuclear localization. Moreover, pUL51 was found in a complex
      with the terminase subunits pUL56 and pUL89. Our data provide evidence that pUL51
      is crucial for HCMV genome cleavage-packaging and may represent a third component
      of the viral terminase complex. Interference with the interactions between the
      terminase subunits by antiviral drugs could be a strategy to disrupt the HCMV
      replication cycle.

PMID- 23175378
TI  - Holoendemic malaria exposure is associated with altered Epstein-Barr virus
      specific CD8(+) T-cell differentiation.
AB  - Coinfection with Plasmodium falciparum malaria and Epstein-Barr virus (EBV) is a
      major risk factor for endemic Burkitt lymphoma (eBL), still one of the most
      prevalent pediatric cancers in equatorial Africa. Although malaria infection has
      been associated with immunosuppression, the precise mechanisms that contribute to
      EBV-associated lymphomagenesis remain unclear. In this study, we used
      polychromatic flow cytometry to characterize CD8(+) T-cell subsets specific for
      EBV-derived lytic (BMFL1 and BRLF1) and latent (LMP1, LMP2, and EBNA3C) antigens
      in individuals with divergent malaria exposure. No malaria-associated differences
      in EBV-specific CD8(+) T-cell frequencies were observed. However, based on a
      multidimensional analysis of CD45RO, CD27, CCR7, CD127, CD57, and PD-1
      expression, we found that individuals living in regions with intense and
      perennial (holoendemic) malaria transmission harbored more differentiated EBV
      specific CD8(+) T-cell populations that contained fewer central memory cells than
      individuals living in regions with little or no (hypoendemic) malaria. This
      profile shift was most marked for EBV-specific CD8(+) T-cell populations that
      targeted latent antigens. Importantly, malaria exposure did not skew the
      phenotypic properties of either cytomegalovirus (CMV)-specific CD8(+) T cells or
      the global CD8(+) memory T-cell pool. These observations define a malaria
      associated aberration localized to the EBV-specific CD8(+) T-cell compartment
      that illuminates the etiology of eBL.

PMID- 23175379
TI  - Impact of mucosal inflammation on oral simian immunodeficiency virus
      transmission.
AB  - Mucosal tissues are the primary route of transmission for most respiratory and
      sexually transmitted diseases, including human immunodeficiency virus (HIV).
      There is epidemiological evidence that genital mucosal inflammation leads to
      enhanced HIV type 1 (HIV-1) transmission. The objective of this study was to
      assess the influence of periodontal inflammation on oral HIV transmission using a
      nonhuman primate model of teeth ligature-induced periodontitis. Simian
      immunodeficiency virus (SIV) was nontraumatically applied to the gingiva after
      moderate gingivitis was identified through clinical and immunologic analyses
      (presence of inflammatory cytokines). Overall oral SIV infection rates were
      similar in the gingivitis-induced and control groups (5 infections following 12
      SIV administrations for each), although more macaques were infected with multiple
      viral variants in the gingivitis group. SIV infection also affected the levels of
      antiviral and inflammatory cytokines in the gingival crevicular fluid, and a
      synergistic effect was observed, with alpha interferon and interferon-inducible
      protein 10 undergoing significant elevations following SIV infection in macaques
      with gingivitis compared to controls. These increases in antiviral and
      inflammatory immune modulators in the SIV-infected gingivitis macaques could also
      be observed in blood plasma, although the effects at both compartments were
      generally restricted to the acute phase of the infection. In conclusion, while
      moderate gingivitis was not associated with increased susceptibility to oral SIV
      infection, it resulted in elevated levels of cytokines in the oral mucosa and
      plasma of the SIV-infected macaques. These findings suggest a synergy between
      mucosal inflammation and SIV infection, creating an immune milieu that impacts
      the early stages of the SIV infection with potential implications for long-term
      pathogenesis.

PMID- 23175381
TI  - Forelimb to hindlimb shape covariance in extant hominoids and fossil hominins.
AB  - Researchers often attempt to use limb proportions to ascertain the locomotor
      repertoires of fossil hominins. This can be problematic as there are few
      skeletons in the fossil record that preserve both a full forelimb and hindlimb;
      therefore, estimates of full limb lengths are typically associated with
      substantial error. In this study, two-block partial least squares analyses were
      used to examine covariation between forelimb and hindlimb elements in extant
      hominoids and fossil hominins. This has the benefit of including both forelimb
      and hindlimb in a type of functional analysis without necessitating an accurate
      length estimate. There is a high degree of covariation between forelimb and
      hindlimb segments in the mixed species sample, particularly in the proximal ulna,
      distal humerus, and proximal/distal femur and that shape covariation is
      significantly correlated with intermembral indices in the extant taxa. Overall,
      the fossil hominins most closely resembled modern humans with the exception of
      analyses utilizing the distal femur where some occupied a unique morphological
      position; thus, some fossil hominins likely possessed locomotor capabilities
      similar to modern humans, whereas others likely represent a unique morphological
      compromise between terrestrial bipedality and other positional behaviors not
      present among extant hominoids.

PMID- 23175382
TI  - Multiple sclerosis risk genotypes correlate with an elevated cerebrospinal fluid
      level of the suggested prognostic marker CXCL13.
AB  - BACKGROUND: The mechanisms of multiple sclerosis (MS) pathogenesis are still
      largely unknown. The heterogeneity of disease manifestations make the prediction
      of prognosis and choice of appropriate treatment protocols challenging. Recently,
      increased cerebrospinal fluid (CSF) levels of the B-cell chemokine CXCL13 was
      proposed as a possible marker for a more severe disease course and conversion
      from clinically isolated syndrome (CIS) to relapsing-remitting MS (RRMS).
      OBJECTIVE: To investigate whether there are genetic susceptibility variants in MS
      that correlate with the levels of CXCL13 present in the CSF of MS patients.
      METHODS: We genotyped the human leukocyte antigens HLA-DRB1 and HLA-A, plus a
      panel of single nucleotide polymorphisms (SNPs) that have been associated with
      susceptibility to MS and then correlated the genotypes with the levels of CXCL13,
      as measured with ELISA in the CSF of a total of 663 patients with MS, CIS, other
      neurological diseases (OND) or OND with an inflammatory component (iOND).
      RESULTS: Presence of the HLA-DRB1*15 and the MS risk genotypes for SNPs in the
      RGS1, IRF5 and OLIG3/TNFAIP3 gene regions correlated significantly with increased
      levels of CXCL13. CONCLUSION: Our results pointed towards a genetic
      predisposition for increased CXCL13 levels, which in MS patients correlates with
      the severity of the disease course. These findings encourage further
      investigation and replication, in an independent patient cohort.

PMID- 23175383
TI  - Impact of obesity on the cost of major colorectal surgery.
AB  - BACKGROUND: The incidence of obesity is increasing in New Zealand. The aim of the
      study was to determine whether obesity impacts on the cost of treating patients
      undergoing major colorectal surgery. METHODS: Between 1 February 2008 and 31 July
      2009, consecutive patients undergoing major colorectal surgery at Christchurch
      Hospital, New Zealand, were enrolled in the study. Body mass index (BMI) and
      waist-to-hip ratios were assessed using standardized techniques. Patients with a
      high surgical risk were identified using established criteria and all patients
      were assessed using the Portsmouth modification of the Physiological and
      Operative Severity Score for the enUmeration of Mortality and morbidity (P
      POSSUM). Cost analysis was performed using a structured query language database.
      Patients were analysed using accepted groupings for BMI, waist circumference and
      waist-to-hip ratio. RESULTS: A total of 372 patients were enrolled in the study,
      of whom 345 were included in the analysis. The incidence of diabetes was
      significantly higher with increased BMI (P = 0.002), whereas all other co
      morbidities, and P-POSSUM values, did not differ between BMI groups. The groups
      were similar in terms of case mix. Treatment of obese patients (BMI at least 30
      kg/m(2)) was significantly more expensive than that of normal weight patients
      (BMI 20-24.9 kg/m(2)): ?10,036 versus ?7390 (P = 0.005). Treatment costs for
      patients with a BMI of 25-29.9 kg/m(2) were next highest (?9048) followed by
      those for patients whose BMI was less than 20 kg/m(2) (?8884). Patients with a
      waist circumference above recognized standards for men and women also cost
      significantly more to treat (?10,063 versus ?7836; P = 0.014). CONCLUSION: Excess
      body fat was associated with higher costs of major colorectal surgery.

PMID- 23175384
TI  - An overview of chromatin modifications.
AB  - The last 15 years have witnessed tremendous progress in elucidating the roles of
      chromatin modifications in transcription regulation, DNA repair, replication,
      recombination, and other genomic processes. In this issue of Biopolymers, a
      series of reviews will summarize recent advances in our understanding of
      chromatin modifying enzymes and explore unresolved questions with respect to
      their regulation and functions in gene expression and other nuclear processes.

PMID- 23175385
TI  - Histone acetyltransferases: Rising ancient counterparts to protein kinases.
AB  - Protein kinases catalyze phosphorylation, a posttranslational modification widely
      utilized in cell signaling. Histone acetyltransferases (HATs) catalyze a
      counterpart posttranslational modification of acetylation which marks histones
      for epigenetic signaling but in some cases modifies non-histone proteins to
      mediate other cellular activities. In addition, recent proteomic studies have
      revealed that thousands of proteins are acetylated throughout the cell to
      regulate diverse biological processes, thus placing acetyltransferases on the
      same playing field as kinases. Emerging biochemical and structural data further
      supports mechanistic and biological links between the two enzyme families. In
      this article, we will review what is known to date about the structure, catalysis
      and mode of regulation of HAT enzymes and draw analogies, where relevant, to
      protein kinases. This comparison reveals that HATs may be rising ancient
      counterparts to protein kinases.

PMID- 23175380
TI  - An increasing proportion of monotypic HIV-1 DNA sequences during antiretroviral
      treatment suggests proliferation of HIV-infected cells.
AB  - Understanding how HIV-1 persists during effective antiretroviral therapy (ART)
      should inform strategies to cure HIV-1 infection. We hypothesize that
      proliferation of HIV-1-infected cells contributes to persistence of HIV-1
      infection during suppressive ART. This predicts that identical or monotypic HIV-1
      DNA sequences will increase over time during ART. We analyzed 1,656 env and pol
      sequences generated following single-genome amplification from the blood and
      sputum of six individuals during long-term suppressive ART. The median proportion
      of monotypic sequences increased from 25.0% prior to ART to 43.2% after a median
      of 9.8 years of suppressive ART. The proportion of monotypic sequences was
      estimated to increase 3.3% per year (95% confidence interval, 2.3 to 4.4%; P <
      0.001). Drug resistance mutations were not more common in the monotypic
      sequences, arguing against viral replication during times with lower
      antiretroviral concentrations. Bioinformatic analysis found equivalent genetic
      distances of monotypic and nonmonotypic sequences from the predicted founder
      virus sequence, suggesting that the relative increase in monotypic variants over
      time is not due to selective survival of cells with viruses from the time of
      acute infection or from just prior to ART initiation. Furthermore, while the
      total HIV-1 DNA load decreased during ART, the calculated concentration of
      monotypic sequences was stable in children, despite growth over nearly a decade
      of observation, consistent with proliferation of infected CD4(+) T cells and
      slower decay of monotypic sequences. Our findings suggest that proliferation of
      cells with proviruses is a likely mechanism of HIV-1 DNA persistence, which
      should be considered when designing strategies to eradicate HIV-1 infection.

PMID- 23175387
TI  - Tipping the lysine methylation balance in disease.
AB  - Genomic instability is a major contributing factor to the development and onset
      of diseases such as cancer. Emerging evidence has demonstrated that maintaining
      the proper balance of histone lysine methylation is critical to preserve genomic
      integrity. Genome-wide association studies, gene sequencing, and genome-wide
      mapping approaches have helped identify mutations, copy number changes, and
      aberrant gene regulation of lysine methyltransferases (KMTs) and demethylases
      (KDMs) associated with cancer and cognitive disorders. Structural analysis of
      KMTs and KDMs has demonstrated the drugability of these enzymes and has led to
      the discovery of small molecule inhibitors. Use of these inhibitors has allowed
      better understanding of the biochemical properties of KMTs and KDMs and
      demonstrated potential for therapeutic use. This review will highlight the methyl
      modifications, KMTs and KDMs associated with cancer and neurological disorders
      and how KMT and KDM and the potential for treatment of these conditions with
      small molecule inhibitors.

PMID- 23175388
TI  - The many facets of MLL1 regulation.
AB  - In the last 20 years, we have witnessed an exponential number of evidences
      linking the human mixed lineage leukemia-1 (MLL1) gene to several acute and
      myelogenous leukemias. MLL1 is one of the founding members of the SET1 family of
      lysine methyltransferases and is key for the proper control of developmentally
      regulated gene expression. MLL1 is a structurally complex protein composed of
      several functional domains. These domains play pivotal roles for the recruitment
      of regulatory proteins. These MLL1 regulatory proteins (MRPs) dynamically
      interact with MLL1 and consequently control gene expression. In this review, we
      summarize recent structural and functional studies of MRPs and discuss emergent
      structural paradigms for the control of MLL1 activity.

PMID- 23175386
TI  - HDAC8 substrates: Histones and beyond.
AB  - The lysine deacetylase family of enzymes (HDACs) was first demonstrated to
      catalyze deacetylation of acetyllysine residues on histones. In subsequent years,
      HDACs have been shown to recognize a large pool of acetylated nonhistone proteins
      as substrates. Recently, thousands of acetylated proteins have been discovered,
      yet in most cases, the HDAC that catalyzes deacetylation in vivo has not been
      identified. This gap has created the need for better in vivo, in vitro, and in
      silico approaches for determining HDAC substrates. While HDAC8 is the best
      kinetically and structurally characterized HDAC, few efficient substrates have
      yet been substantiated in vivo. In this review, we delineate factors that may be
      important for determining HDAC8 substrate recognition and catalytic activity,
      including structure, complex formation, and post-translational modifications.
      This summary provides insight into the challenges of identifying in vivo
      substrates for HDAC8, and provides a good vantage point for understanding the
      variables important for predicting HDAC substrate recognition.

PMID- 23175389
TI  - STUbLs in chromatin and genome stability.
AB  - Chromatin structure and function is based on the dynamic interactions between
      nucleosomes and chromatin-associated proteins. In addition to the other post
      translational modifications considered in this review issue of Biopolymers,
      ubiquitin and SUMO proteins also have prominent roles in chromatin function. A
      specialized form of modification that involves both, referred to as SUMO-targeted
      ubiquitin ligation, or STUbL [Perry, Tainer, and Boddy, Trends Biochem Sci, 2008,
      33, 201-208], has significant effects on nuclear functions, ranging from gene
      regulation to genomic stability. Intersections between SUMO and ubiquitin in
      protein modification have been the subject of a recent comprehensive review
      [Praefcke, Hofmann, and Dohmen, Trends Biochem Sci, 2012, 37, 23-31]. Our goal
      here is to focus on features of enzymes with STUbL activity that have been best
      studied, particularly in relation to their nuclear functions in humans, flies,
      and yeasts. Because there are clear associations of disease and development upon
      loss of STUbL activities in metazoans, learning more about their function,
      regulation, and substrates will remain an important goal for the future.

PMID- 23175390
TI  - The protein arginine deiminases: Structure, function, inhibition, and disease.
AB  - The post-translational modification of histones has significant effects on
      overall chromatin function. One such modification is citrullination, which is
      catalyzed by the protein arginine deiminases (PADs), a unique family of enzymes
      that catalyzes the hydrolysis of peptidyl-arginine to form peptidyl-citrulline on
      histones, fibrinogen, and other biologically relevant proteins. Overexpression
      and/or increased PAD activity is observed in several diseases, including
      rheumatoid arthritis, Alzheimer's disease, multiple sclerosis, lupus, Parkinson's
      disease, and cancer. This review discusses the important structural and
      mechanistic characteristics of the PADs, as well as recent investigations into
      the role of the PADs in increasing disease severity in RA and colitis and the
      importance of PAD activity in mediating neutrophil extracellular trap formation
      through chromatin decondensation. Lastly, efforts to develop PAD inhibitors with
      excellent potency, selectivity and in vivo efficacy are discussed, highlighting
      the most promising inhibitors.

PMID- 23175392
TI  - Ag nanorod based surface-enhanced Raman spectroscopy applied to bioanalytical
      sensing.
AB  - Recent progress in substrate nanofabrication has led to the development of Ag
      nanorod arrays as uniform, reproducible, large area SERS-active substrates with
      high signal enhancement. These novel nanostructures fabricated by oblique angle
      vapor deposition (OAD) offer a robust platform for the rapid detection of
      biological agents and open new perspectives for the development and integration
      of biomedical diagnostic for clinical and therapeutic applications. Ag nanorod
      arrays have been investigated as SERS-active substrates for the detection and
      identification of pathogens, including bacteria and viruses, as well as to
      evaluate the potential of this biosensing platform for bio-recognition of high
      affinity events using oligonucleotide-modified substrates. This review summarizes
      the various nanostructured substrates designed for SERS-based applications,
      highlights the nanofabrication methodology used to produce Ag nanorod arrays,
      outlines their morphological and physical properties, and provides a summary of
      the most recent uses of these substrates for clinical diagnostic and biomedical
      applications.

PMID- 23175393
TI  - [Understanding homicides in Latin America: poverty or institutionalization?].
AB  - Homicides occur the world over, but they are not homogeneously distributed by
      geographical areas (continents, countries, regions), either over long or short
      periods of time, or in social groups, namely age, gender, social class or
      ethnicity. Why are there more homicides in some countries than in others? Why do
      killings increase in some countries, while they decrease in others? There are two
      fundamental schools of thought for social explanations of crime and violence:
      those attributing its origins to poverty and inequality and those blaming
      institutionalization or social norms. To discuss these theories, this paper
      analyzes and compares the changes in Colombia, Venezuela and Brazil in the first
      decade of the twenty-first century, where the homicide rate has decreased,
      increased and remained the same, respectively. Using the measurement of six
      variables (poverty, inequality, unemployment, national wealth, human development
      and the rule of law) and the technique of trajectory analysis, the results
      revealed that institutionalization is more to blame for the change than poverty
      and inequality. The text concludes that poverty and inequality affect crime and
      homicides, although not directly, but mediated by the institutions instead.

PMID- 23175394
TI  - [Homicides in the Americas region: magnitude, distribution and trends, 1999
      2009].
AB  - The scope of this study was to describe the magnitude and distribution of deaths
      by homicide in the Americas and to analyze the prevailing trends. Deaths by
      homicide (X85 to Y09 and Y35) were analyzed in 32 countries of the Americas
      Region from 1999 to 2009, recorded in the Mortality Information System/Pan
      American Health Organization. A negative binomial model was used to study the
      trends. There were around 121,297 homicides (89% men and 11% women) in the
      Americas, annually, predominantly in the 15 to 24 and 25 to 39 year age brackets.
      In 2009 the homicide age-adjusted mortality rate was 15.5/100,000 in the region.
      Countries with lower rates/100,000 were Canada (1.8), Argentina (4.4), Cuba
      (4.8), Chile (5.2), and the United States (5.8), whereas the highest
      rates/100,000 were in El Salvador (62.9), Guatemala (51.2), Colombia (42.5),
      Venezuela (33.2), and Puerto Rico (25.8). From 1999-2009, the homicide trend in
      the region was stable. They increased in nine countries: Venezuela (p<0.001),
      Panama (p<0.001), El Salvador (p<0.001), Puerto Rico (p<0.001); decreased in four
      countries, particularly in Colombia (p<0.001); and were stable in Brazil, the
      United States, Ecuador and Chile. The increase in Mexico occurred in recent
      years. Despite all efforts, various countries have high homicide rates and they
      are on the increase.

PMID- 23175395
TI  - [Multicentric study of deaths by homicide in Latin American countries].
AB  - This article is a descriptive epidemiological study of deaths by homicide in
      Latin American countries (Argentina, Brazil, Colombia and Mexico) from 1990 to
      2007. Deaths due to external causes and homicides, as codified in the 9th and
      10th revisions of the International Classification of Diseases/ICD, were analyzed
      considering sex, age and manner of assault. The numbers, ratios and adjusted
      rates for deaths by homicide are presented. A linear regression model was used to
      ascertain the trend of homicide rates by age group. During the period, 4,086,216
      deaths from external causes and 1,432,971 homicides were registered in these
      countries. Deaths from external causes rose 54.5% in Argentina but fell in the
      other countries (37% in Mexico, 31.8% in Colombia, and 8.1% in Brazil). The ratio
      for deaths by homicide for both sexes was 9.1 in Colombia, 4.4 in Brazil and 1.6
      in Mexico, using the Argentinian rates as a benchmark. There were differences in
      the evolution of homicide rates by age and sex in the countries: the rate rose in
      Brazil and fell in Colombia for all age groups. The need to prioritize young
      males in public policies related to health care and prevention is stressed, as
      well as the need for the region to adopt inclusive policies and broaden and
      consolidate democracy and the rights of inhabitants.

PMID- 23175396
TI  - [Deaths by homicide in Mexico: trends, socio-geographical variations and
      associated factors].
AB  - This study seeks to analyze the trend of homicide rates (total and by firearm) in
      Mexico between 1990 and 2009 and identify the variables that best explain the
      geographical variations of these rates in the 2008-2009 two-year period. Homicide
      rates, adjusted for age, were calculated for both sexes between 1990 and 2009 and
      for each state in 2008-2009. Factors associated with the interstate variations in
      the homicide rates were identified using multiple linear regression analysis.
      Results show that the homicide rate in Mexico decreased between 1990 and 2007,
      but doubled over the last two years (from 7.6 to 16.6 per 100,000). In 2009, the
      male homicide rate was almost 9 times higher than the female rate and about two
      thirds of homicides involved firearms. Multivariate analysis reveals that
      impunity, drug trafficking, alcohol and drug consumption and school dropout in
      basic education - in that order - are key factors for understanding the
      geographical variations in homicide rates in Mexico in 2008-2009. Findings
      suggest that to reduce the number of homicide victims and spatial variations in
      the rate, it is necessary not only to fight the drug cartels, but above all to
      implement structural reforms in the criminal justice system and reduce the
      socioeconomic disparities among states.

PMID- 23175397
TI  - [Deaths by homicide in Medellin, 1980-2007].
AB  - The Colombian city of Medellin has faced a severe problem of violence and
      homicide. The goal of this retrospective, descriptive-analytical study was to
      assess the magnitude, distribution, most salient characteristics and possible
      explanations for the problem between 1980 and 2007. Data were obtained from
      official databases, hospital records and the available literature, and a focus
      group was set up. There was a dramatic rise in homicides in the city in the time
      interval studied, with a total of 84,863 documented murders. Ninety-three percent
      of the victims were male. The 20 to 29 year-old age group was the most affected.
      Males in this age group, during the worst year of the period (1991), registered
      an astounding murder rate of 1,709 per 100,000. Even males in the 15 to 19 year
      age group and the older brackets saw high murder rates. The most common victims
      were from the lower and lower-middle socioeconomic strata, as has been observed
      elsewhere in the region. Serious problems were identified in information and in
      the provision of services. The impact of homicide on the delivery of healthcare
      services is discussed and a series of tasks for the healthcare sector in the
      control of this type of violence is proposed.

PMID- 23175398
TI  - [Homicides involving firearms in Argentina between 1991 and 2006: a multilevel
      analysis].
AB  - The influence of variables at different levels of organization and the effect of
      time on the occurrence of firearm-related homicides (FRH) in Argentina between
      1991 and 2006 was analyzed using multilevel analysis. A three-level Poisson
      regression model was used. The first level corresponded to the distribution of
      the number of FRH by sex and age group for each administrative region and (four
      year) period; the second corresponded to the variation over time in the interior
      of each administrative region; the third modeled the variation between
      administrative regions in accordance with the Level of Urbanization, Percentage
      of Homes with Unsatisfied Basic Needs and the Percentage of Working Adults. There
      were 15,067 FRH in persons aged 14 and over between 1991 and 2006 in the 493
      administrative regions. The risk of death was higher in males and persons of 15
      to 29 years of age; ages above that were associated with a lower risk. The
      influence of age was greater in central-urban zones and between 1999 and 2002
      than during other periods. The level of urbanization was the socioeconomic
      variable most strongly associated with FRH risk. The risk of death from FRH was
      1.6 times higher in central-urban zones compared with non-central zones. In both
      zones, the risk was highest between 1999 and 2002.

PMID- 23175399
TI  - [Three phases of homicidal violence in Venezuela].
AB  - Venezuela was considered one of the least violent countries in Latin America,
      however by 2010 it was among the countries with the highest homicide rate. This
      article analyzes the evolution of homicides in Venezuela between 1985 and 2010
      and proposes the existence of three stages which correspond to trends in social
      and political institutions of the country. The first from 1985 to 1993,
      characterized by the looting of 1989 and the coups d'etat of 1992, when for the
      first time the homicide rate rose from 8 to 20. The second phase from 1994 to
      1998 was a recovery period of the institutional and political stability when the
      homicide rate remained constant at around 20. The third phase began in 1999 with
      the H Chavez government and the institutional destruction that comes with the
      Bolivarian revolution and caused an increase in the rate of 20 to 57 homicides
      per 100 thousand inhabitants. This article argues that the explanation for the
      changes in the phases is to be found in the transformation of social and
      political institutions.

PMID- 23175400
TI  - [Morbidity and mortality of young Brazilian men due to aggression: expression of
      gender differentials].
AB  - Mortality, hospitalization and emergency attendance visits for assault in Brazil,
      from 1996 to 2007 were analyzed. The data sources are the Mortality Information
      System/SIM, the Hospital Information System/SIH and the Surveillance System of
      Violence and Injuries/VIVA of the Ministry of Health. It was focused on males in
      the 15 to 29 year-old age group, and other variables related to the victim, the
      aggressor and the event. The male/ woman distribution was 11.6 times higher for
      mortality, 4.5 times for hospitalization and 2.8 times for hospital emergency
      treatment. In 2007 the rate of 15 to 29 year-old men was 92.8/100,000
      inhabitants. The Southeast and Northeast have the highest incidence and
      prevalence. The conclusion was that the male/female differential rates occurs
      during adolescence, intensifies in early adulthood, and despite decreasing in
      intensity, continues until death. Cultural gender models and socio-structural
      aspects were examined to explain such marked differences.

PMID- 23175401
TI  - [Homicide and public security indicator trends in the city of Sao Paulo between
      1996 and 2008: a time-series ecological study].
AB  - The scope of this paper was to analyze the association between homicides and
      public security indicators in Sao Paulo between 1996 and 2008, after monitoring
      the unemployment rate and the proportion of youths in the population. A time
      series ecological study for 1996 and 2008 was conducted with Sao Paulo as the
      unit of analysis. Dependent variable: number of deaths by homicide per year. Main
      independent variables: arrest-incarceration rate, access to firearms, police
      activity. Data analysis was conducted using Stata.IC 10.0 software. Simple and
      multivariate negative binomial regression models were created. Deaths by homicide
      and arrest-incarceration, as well as police activity were significantly
      associated in simple regression analysis. Access to firearms was not
      significantly associated to the reduction in the number of deaths by homicide
      (p>0,05). After adjustment, the associations with both the public security
      indicators were not significant. In Sao Paulo the role of public security
      indicators are less important as explanatory factors for a reduction in homicide
      rates, after adjustment for unemployment rate and a reduction in the proportion
      of youths. The results reinforce the importance of socioeconomic and demographic
      factors for a change in the public security scenario in Sao Paulo .

PMID- 23175403
TI  - An ecosysthemic vision of homicide.
AB  - Four cities were analyzed in term of homicide rates, namely two Brazilian and two
      Argentinian cities. In each country, a city with high homicide rates and another
      with low rates were studied over the same three-year period. The theoretical
      approach of complex systems was used as it examines the link between the local
      system in its internal interconnections, the influence of the external
      environment and psychic engagement, namely the interpenetration between the
      social system and subjectivities. The emphasis of the study and the comparisons
      were conducted using qualitative research with observation, the use of interviews
      and focal groups. The results show that in locations with high or low homicide
      rates, there is synergy between the external environment (macrosocial and
      macroeconomic politics), the social system (social organization, local
      government, community participation) and subjectivity, whether it is in the
      construction of solidarity or social disintegration. Studies about changes in the
      violent social systems show that persistent and coordinated actions that
      articulate economic, social and educational investments as measures to prevent
      and restrain homicides have a positive impact in historical terms.

PMID- 23175402
TI  - [Violence-related deaths in Argentina: two case studies in the cities of Venado
      Tuerto and San Rafael].
AB  - This article presents the results of a comparative study of two Argentinian
      cities, namely Venado Tuerto and San Rafael, which revealed different trends in
      the rates of firearm-related homicides. The methodology combined two strategies
      of analysis: semi-structured interviews with key informants (municipal and
      provincial government agents in different areas of management, as well as members
      of non-governmental organizations) and focus groups with actors involved in
      medical care, education, and religious institutions. The results suggest little
      difference between cities in which rates have increased and those in which rates
      have decreased. The most significant difference was that in Venado Tuerto a
      greater fragility of public institutions was observed due to the lack of
      articulation between such institutions. In San Rafael, the actors interviewed
      attribute the low level of conflict to a violence prevention network in which
      provincial and municipal agencies interact. Although neither city is violent at
      the most critical Latin American levels, the different results shown in Venado
      Tuerco and San Rafael indicate the possibility of bringing institutions together
      in a joint framework of conversations, agreements and policies.

PMID- 23175404
TI  - [The quality of information systems on violence-related deaths in Argentina and
      Brazil between 1990 and 2010].
AB  - Violence-related deaths are a public health issue by virtue of the magnitude of
      their impact on society and on the health services. A study of the descriptive
      temporal trend was conducted using the official national information systems of
      violence-related mortality in Argentina and Brazil for the period from 1990 to
      2010. Indicators were created to evaluate information quality by sex, age, and
      cause of death. The results demonstrate a temporal trend of improvement in the
      quality of the information systems. This trend is repeated especially when
      violence-related deaths are analyzed, with a decrease in the number of records
      for violence-related death of undetermined intent; as well as a high percentage
      of firearm-related deaths of undetermined intent in Argentina. The analysis of
      the quality of information systems regarding violence-related deaths makes it
      possible to detect problems and orient actions in order to obtain better quality
      information and therefore permit improvement in the creation of preventive public
      policies.

PMID- 23175405
TI  - [The participation of the nutritionist in primary health care in a large urban
      center].
AB  - Nutritionists are important professionals for ensuring the implementation of
      health promotion, treatment and rehabilitation. However, their participation in
      primary healthcare from a quantitative standpoint is limited. The city of Sao
      Paulo has experienced an uneven urbanization process triggering new problems of
      insecurity in terms of food and nutrition. This article analyzes the performance
      of the primary healthcare nutritionist in a large urban center. It is a
      quantitative study that used data from the Municipal Health Department,
      population data of Sao Paulo and a semi-structured questionnaire applied in
      individual interviews. All regions of the city are found to have fewer
      nutritionists than the recommendation of the Federal Council of Nutritionists.
      There are 123 nutritionists in the basic healthcare network and 51 in the Family
      Health Support Nuclei (FHSN) (57.3%). Each nutritionist from the FHSN accompanies
      7.1 family health strategy teams on average. The age groups corresponding to
      children are less frequently seen by nutritionists. Comparing the activities, the
      transition from a model of primary health care focused on individual care to a
      model that prioritizes group care was observed.

PMID- 23175406
TI  - [Discourses of primary mental healthcare teams on addressing gender violence
      within the context of relationships].
AB  - Violence against women within relationships is a problem which is in the public
      eye and is mainly associated with the gender factor. It is therefore crucial to
      incorporate a gender perspective in order to understand and intervene in this
      phenomenon. A qualitative study was conducted using semi-structured interviews
      and applying content analysis, to analyze if the declared discourse of the
      Primary Mental Healthcare teams in Valparaiso (physicians, psychologists, social
      workers), regarding tackling violence against women within the context of a
      relationship includes perceptions, knowledge and ideas based on the gender
      perspective. There is a general consensus on how to deal with battered women, as
      for all of them it is very important to create an empathic, therapeutic space of
      containment. Multidisciplinary and intersectoral work is considered important in
      the work discussions and the risk of repeat victimization was mentioned. In
      general, there was no intention to empower women from a gender perspective, with
      the exception of some psychologists (males and females). This work could lead to
      a critical evaluation of the various discourses of Primary Mental Healthcare
      Teams in addressing gender-based violence.

PMID- 23175407
TI  - [AIDS prevention in the period of sexual initiation: aspects of the symbolic
      dimension of the conduct of young men].
AB  - To acquire an in-depth grasp of the non-consistent use of condoms, an attempt was
      made to characterize aspects of the symbolic meanings of sexual conduct in a
      group of young males. Interviews with forty-two subjects whose sexual initiation
      occurred in the late 1990s were qualitatively assessed by an analysis of
      statements interpreted under the theoretical perspectives of sexual scripts and
      male lifestyle and values. Participants emphasized the importance of blood
      testing and a biographical analysis of their partners (to generate 'trust') and
      tended to use personal criteria to assess the state of their partners' health.
      They established a dyadic typology of these relationships divided into
      "infrequent" and "steady" partners respectively, exercising two kinds of
      approaches to condom use, namely prevention of AIDS-STD and pregnancy on the one
      hand and only for pregnancy prevention on the other. The narratives seem to
      result, among other factors, from a biomedical approach to aspects of their sex
      lives and a desire for a stable and monogamous sexual-affective relationship. The
      important and recent changes in the intrapsychic and interpersonal sexual scripts
      do not seem to be currently accompanied by equally profound changes in cultural
      scripts or male lifestyle and values.

PMID- 23175408
TI  - [Self-medication among university students: the influence of the field of study].
AB  - The scope of this paper was to investigate the influence of a university
      student's field of study upon self-medication. A cross-sectional study was
      conducted through the administration of questionnaires on the profile of the
      respondents, self-medication and other healthcare-related issues. In all, 342
      students from different fields of study were interviewed, 81 of which were from
      the health area. Of the respondents, 37% reported self-medicating in the last
      fortnight. The most common health problems for self-medication in this period
      were general pain (90.4%) and analgesics and antipyretics were the most common
      form of medication. It was observed that being female (p=0.049), as well as the
      fact of having health insurance (p=0.036), were significantly associated with
      self-medication and that studying in the health area was not associated with self
      medication (0.139). However, it was found that the influence of advertising
      (p<0.001), old prescriptions (p=0.041), pharmacists or pharmacy employees
      (p=0.005), as well as friends, neighbors and relatives (p=0.003) were more
      significant among university students who were not within the health area, though
      the influence of acquired knowledge (p<0.001) is more significant among students
      in the health area.

PMID- 23175409
TI  - [Prescriptions for anorectic psychotropic drugs in the municipality of Juiz de
      Fora, Minas Gerais, Brazil].
AB  - Obesity is a serious public health issue of epidemic proportions. Although drug
      therapy is one of the therapeutic approaches, it should be preceded by a change
      in eating habits along with regular exercise. This study assessed prescription of
      such drugs in 2009, in Juiz de Fora, Minas Gerais, Brazil. Data were collected
      from consumption bulletins sent monthly to the municipal sanitary surveillance
      agency (VISA), and from the Brazilian National Management System of Controlled
      Products. Of the 7,759 notifications assessed, 93.3% were dispensed by
      prescription pharmacies and 6.7% by drugstores. Of that total, 55.4% were for
      amphepramone, 33.1% for femproporex, and 11.5% for mazindol. The three drugs had
      a larger consumption rate in the municipality (daily defined dose/1,000
      inhabitants/day) than in the country as a whole, during the period under study.
      The professional with the highest prescription rate was responsible for 3,535
      prescriptions. All of these were dispensed by prescription pharmacies, a single
      outlet being responsible for 99.5% of these prescriptions. This scenario shows
      that anorectic psychotropic drug prescription is a relevant public health issue
      and the criteria for monitoring the prescription and consumption of these drugs
      should be re-evaluated.

PMID- 23175410
TI  - [User satisfaction and responsiveness in the healthcare services at Fundacao
      Oswaldo Cruz].
AB  - The paper discusses the results of research into user satisfaction in three
      healthcare facilities at Oswaldo Cruz Foundation in Rio de Janeiro. The analysis
      is based on the concepts of user satisfaction and responsiveness. Perceptions and
      opinions of outpatients from Instituto de Pesquisa Evandro Chagas, Instituto
      Fernandes Figueira and Centro de Saude Escola Germano Sinval Faria were
      investigated. Intention samples were drawn for each institution and a total of
      1.339 valid questionnaires were obtained. The study found that patients are
      satisfied with healthcare at Fiocruz, especially with health professionals.
      Nevertheless, restroom hygiene and privacy during consultations were less well
      evaluated. The improvement of these aspects depends not only on financial and
      technological investments but on changes in organizational culture. The first
      part of the paper discusses the literature on user satisfaction and
      responsiveness, with the definition of the categories that guided the study. The
      methodology is then presented as well as the four health services dimensions
      assessed - dignity, agility, facilities and communication - and the results are
      analyzed.

PMID- 23175411
TI  - [Self-reported health status in adolescents, adults and the elderly].
AB  - The scope of this study was to verify the prevalence and associated factors of
      self-reported health status as regular/bad. A cross-sectional, population-based
      study was conducted in Pelotas. The sample size comprised 820 adolescents, 2715
      adults and 385 elderly. Self-reported health status was investigated via the
      question: "How do you rate your health?" Data on demographics, socioeconomic,
      behavioral, and health-related characteristics of individuals were gathered.
      Adjusted prevalence ratios were estimated through the Poisson regression.
      Prevalence of reporting health status as regular or bad was 12.1%, 22.3% and
      49.4% in adolescents, adults and the elderly, respectively. Adolescents with
      lower economic status and schooling had higher prevalence of regular/bad self
      reported health. Among adults and the elderly, women and older men with lower
      economic status and some morbidity presented a higher proportion of regular/bad
      self-reported health. In conclusion, individuals perceive health not only as the
      absence of a disease, but also as a construct related to social, demographic and,
      to a lesser extent, behavioral aspects. Health approaches must recognize this
      fact and transcend the simplistic model where health is dichotomized into the
      sick and the non-sick.

PMID- 23175412
TI  - [Trends in frequency of consumption of beans assessed by means of a telephone
      survey in Brazilian state capitals between 2006 and 2009].
AB  - The scope of this paper was to analyze the trends of frequency of consumption of
      beans between the years 2006 and 2009 in the Brazilian capitals. This is a
      historical series using the Vigitel database for all Brazilian state capitals.
      Consumption of beans was described in terms of relative frequency and the trend
      was assessed using Poisson regression. Between 65.79% (2009) and 71.85% (2006) of
      participants reported consuming beans five or more days per week. The capitals
      Goiania, Belo Horizonte, Palmas, Brasilia and Cuiaba were in the highest
      frequency range of consumption throughout the study period. Individuals with a
      BMI in the appropriate and low weight category had the highest frequencies of
      consumption in comparison with the overweight and the obese. A significant
      reduction trend in the consumption of beans per year of the research, except for
      the 45 to 54-year-old range, was detected. The conclusion drawn was that there
      has been a significant reduction in the consumption of beans in the Brazilian
      population and the adoption of monitoring and incentive policies is necessary due
      to the benefits of the legume.

PMID- 23175413
TI  - [Beliefs and behavior patterns of individuals with coronary artery disease].
AB  - The study described beliefs and behavior patterns related to causes and control
      measures of coronary artery disease (CAD). A hundred adults in an outpatient
      clinic in Salvador in the state of Bahia were interviewed. The results were
      analyzed via the qualitative analysis technique. It predominantly involved
      married and unemployed black men, aged <60 years, with low schooling and income.
      The average beliefs on the cause of CAD was 1.53 per participant and blamed
      behavioral, biological, relational and religious factors, and represented
      excesses related to day-to-day tensions and eating habits. Most of the
      participants did not consider the disease to be chronic and believed that
      treatment would be temporary and they would be cured. The average beliefs for
      control measures were of 1.45, with dietary measures and medication. A sedentary
      lifestyle was the norm and reducing smoking and alcohol, using less salt and
      saturated fat in the preparation of meals, consuming white meat, cooked and
      industrialized food was seen as the answer. Only 66% complied with medical
      prescriptions. Lack of understanding of the causes and control measures of CAD
      makes the implementation of medical care, better living and health conditions and
      self-care essential.

PMID- 23175414
TI  - [Normative measures of the Health in the School Program: content analysis
      associated with ATLAS TI software].
AB  - The scope of this study was to analyze the normative measures issued about the
      Health in the School Program in order to ascertain the contribution and
      participation of the health and education sectors in the creation and
      implementation of the Program, since its success was based upon intersectoral
      action between them. The technique of content analysis proposed by Bardin,
      associated with ATLAS TI 5.2 software was used to conduct the research. The study
      revealed that the participation of the health and education sectors in the Health
      in the School Program is not well-balanced, pointing to the predominant role of
      health in areas such as financing and the centralization of the adhesion and
      coordination process of the Intersectoral Commission on Education and Health in
      the School.

PMID- 23175415
TI  - [Influence of the nutritional status in the risk of eating disorders among female
      university students of nutrition: eating patterns and nutritional status].
AB  - The scope of this paper was to evaluate the relationship between changes in
      eating behavior associated with dissatisfaction with body image, and the
      nutritional status of female university students of nutrition. A cross-sectional
      study was conducted among 175 female students of nutrition (ENUT/UFOP). The
      Eating Attitudes Test-26 (EAT-26) and Body Shape Questionnaire (BSQ) were applied
      and anthropometric measurements were taken. 21.7% of the students were found to
      be high risk in terms of eating disorders, and 13.7% declared dissatisfaction
      with their body image. The majority of students with positive results in the BSQ
      and EAT-26 tests were eutrophic. The students who were overweight, with elevated
      body fat percentage (% BF) and waist circumference (WC) had a 5-9 times greater
      risk of change in eating habits. There was a positive association between the
      anthropometric parameters with high scores in the EAT-26 and BSQ questionnaires.
      The future dietitians who are overweight, with increased body fat and waist
      circumference were more likely to be dissatisfied with their body image and
      develop eating disorders. The use of other anthropometric parameters, in addition
      to BMI, may prove useful in screening individuals susceptible to the emergence of
      excessive concerns with weight and diet.

PMID- 23175416
TI  - [Policy, management and participation in health: a reflection based on Habermas'
      theory of communicative action].
AB  - The article discusses the appropriation of the theory developed by Habermas to
      analyze health policies and management. The fundamental concepts of the
      discursive theory of democracy as a deliberative policy, procedural democracy,
      the public sphere and civil society are analyzed. An attempt is made to
      demonstrate that the concepts of deliberative policies are grounded on basic
      theoretical categories of Habermas's conception of language, namely the theory of
      communicative action (TCA): lifeworld and system; communicative action and
      discourse; the ideal speech situation. The possibility of translating the
      categories presented in analytical categories, such as the experiences of social
      participation in deliberative forums and the results for the formulation and
      implementation of policies and health management is discussed. The conclusion
      drawn is that the theoretical categories reveal great explanatory potential and
      analytical categories are important provided that they are mediated and
      contextualized.

PMID- 23175418
TI  - [Nutritional status of children attended in day-care-centers and food
      (in)security of their families].
AB  - The scope of this study was to examine associated factors with overweight,
      stunting and underweight in children attending state day care centers of Joao
      Pessoa, as well as to describe the situation of food (in)security of their
      families. A cross-sectional study was conducted with a sample of 250 children.
      Socioeconomic, maternal and child variables were studied. The nutritional status
      of children was evaluated considering the height-for-age and weight-for-height
      indices. Household food security was assessed using the Brazilian Scale of Food
      Insecurity. The proportions of stunting, underweight and overweight were 7.6%,
      1.6% and 6.4% respectively. The associated factors with short stature were low
      maternal stature and incomplete vaccination. In relation to low weight, the
      associated factor was maternal age under 20 years. The overweight child was
      associated with excessive maternal weight and maternal short stature. In 59.6% of
      families, there was food and nutrition insecurity, the mild form being more
      frequent (32.4%). Overweight and stunting were found to be the most common
      nutritional disorders in this study, constituting priorities that should be
      considered in current public policies.

PMID- 23175417
TI  - [The impact of dental trauma on quality of life of children and adolescents: a
      critical review and measurement instruments].
AB  - Dental trauma constitutes a public health problem with a marked prevalence among
      Brazilian children and adolescents. Furthermore, it can lead to irreparable
      dental loss, which makes it important to evaluate this condition using
      instruments of oral health related to quality of life (OHRQoL). Based on this, a
      review of the literature sought to expose indices that may assess the evaluation
      of quality of life among Brazilians with dental trauma, as well as discuss the
      state of the art of publications about this condition on their OHRQoL followed by
      a discussion of the output encountered on the subject. With this in mind the
      articles published from 1980 to June/2011 located on databases (Pubmed, VHL,
      Google Scholar) or manually in the references of selected publications were
      prioritized. It was revealed that there is no specific instrument for dental
      trauma. It is therefore necessary to assess the OHRQoL in children and
      adolescents with indices found in the literature. Once this has been done, as yet
      unresolved questions about the impact of dental trauma on OHRQoL can be answered.

PMID- 23175419
TI  - [Resource allocation systems for health service providers - the international
      experience].
AB  - This article presents the traditional ways of allocating resources to health
      service providers and focuses on the presentation and discussion of alternative
      experiences found in the international context. It also shows the current trends
      in the OECD countries, involving the adoption of mixed systems or performance
      related bonuses, the latter being predominantly referred to the effects on the
      health of the population, i.e. the effectiveness of the health services. It
      further stresses the tendency to adopt resource allocation systems that are
      differentiated according to the level of care provider: to primary care centers,
      responsible for the health of the population of a given territory, a per capita
      adjusted for risk factor is granted (or, in some cases, resource allocation
      defined for lines of care), while in other cases hospitals are either paid
      according to a performance-adjusted global budget or through prospective payment
      per procedure.

PMID- 23175421
TI  - Climate change and leptospirosis.

PMID- 23175422
TI  - Few layer graphene to graphitic films: infrared photoconductive versus bolometric
      response.
AB  - We report a comparative study of the performance of infrared (IR) photoconductive
      and bolometric detectors fabricated from few layer graphene (FLG) to graphitic
      films obtained by different methods. FLG films grown directly on insulating
      substrates with the aid of residual hydrocarbons and polymethylmethacrylate
      (PMMA) carbon sources show an IR photoresponse of 73% which is far higher
      compared to the FLG films (6-14%) obtained by CVD and Scotch tape methods. The
      photoconductive nature of FLG films is due to generation of photoexcited charge
      carriers. On the other hand, the photoresponse of the bulk graphitic films is
      bolometric in nature where the resistance changes are due to thermal effects. The
      IR photoresponse from these graphitic films is correlated with the Raman peak
      intensities which are very sensitive to the nature of the FLG.

PMID- 23175423
TI  - Novel electrochemical method for the characterization of the degree of chirality
      in chiral polyaniline.
AB  - A novel method to indicate the degree of chirality in polyaniline (PANI) was
      developed. The (D-camphorsulfonic acid)- and (HCl)-PANI-based electrodes
      exhibited significantly different electrochemical performances in D- and L
      Alanine (Ala) aqueous solution, respectively, which can be used for the
      characterization the optical activity of chiral PANI. Cyclic voltammogram, tafel,
      and open circuit potential of PANI-based electrodes were measured within D- and L
      Ala electrolyte solution, respectively. The open circuit potentials under
      different reacting conditions were analyzed by Doblhofer model formula, in which
      [C(+)](poly1)/[C(+)](poly2) was used as a parameter to characterize the degree of
      chirality in chiral PANI. The results showed that [C(+)](poly1)/[C(+)](poly2) can
      be increased with increasing concentrations of (1S)-(+)- and (1R)-(-)-10
      camphorsulfonic acid. In addition, we detected that appropriate response time and
      lower temperature are necessary to improve the degree of chirality.

PMID- 23175424
TI  - Simultaneous determination of acetylsalicylic acid and salicylic acid in human
      plasma by isocratic high-pressure liquid chromatography with post-column
      hydrolysis and fluorescence detection.
AB  - A selective, sensitive and rapid high-performance liquid chromatography method
      with post-column hydrolysis and fluorescence detection was developed for the
      simultaneous quantification of acetylsalicylic acid and its metabolite salicylic
      acid in human plasma. Following the addition of 2-hydroxy-3-methoxybenzoic acid
      as internal standard and simple protein precipitation with acetonitrile, the
      analytes were separated on a ProntoSIL 120 C18 ace-EPS column (150 * 2 mm, 3 um)
      protected by a C8 guard column (5 um). The mobile phase, 10 mm formic acid in
      water (pH 2.9) and acetonitrile (70:30, v/v), was used at a flow rate of 0.35
      mL/min. After on-line post-column hydrolysis of acetylsalicylic acid (ASA) to
      salicylic acid (SA) by addition of alkaline solution, the analytes were measured
      at 290 nm (lambdaex ) and 400 nm (lambdaem ). The method was linear in the
      concentration ranges between 0.05 and 20 ng/MUL for both ASA and SA with a lower
      limit of quantification of 25 pg/MUL for SA and 50 pg/MUL for ASA. The limit of
      detection was 15 pg/MUL for SA and 32.5 pg/MUL for ASA. The analysis of ASA and
      SA can be carried out within 8 min; therefore this method is suitable for
      measuring plasma concentrations of salicylates in clinical routine.

PMID- 23175425
TI  - Inhibitory effects of Akebia quinata ethanol extract on TNF-alpha-mediated
      vascular inflammation in human aortic smooth muscle cells.
AB  - Atherosclerosis is a chronic inflammatory disease of the arterial wall. The
      expression of adhesion molecules in aortic smooth muscle cells facilitates the
      accumulation of transmigrated leukocytes within the atherosclerotic vascular
      wall. The stem of Akebia quinata (A. quinata) has previously been used as a crude
      drug for treating urinary disorders and inflammatory disease in Korea, China and
      Japan. In the present study, we investigated the effect of an A. quinata ethanol
      extract (AQEE) on the expression of adhesion molecules and cyclooxygenase-2 (COX
      2) in tumor necrosis factor alpha (TNF-alpha)-induced human aortic smooth muscle
      cells (HASMCs). The results of the present study demonstrated that AQEE
      attenuated intercellular adhesion molecule 1, E-selectin and COX-2 expression in
      TNF-alpha-stimulated HASMCs and inhibited THP-1 cell adhesion to activated
      HASMCs. Furthermore, AQEE suppressed the TNF-alpha induced phosphorylation of p38
      mitogen-activated protein kinase (MAPK) and reduced nuclear factor kappaB (NF
      kappaB; p65) nuclear translocation. The present study demonstrated that AQEE
      possesses anti-inflammatory properties and regulates TNF-alpha-induced expression
      of adhesion molecules by inhibition of the p38 MAPK/NF-kappaB signaling pathway.

PMID- 23175426
TI  - Hardness potential derivatives and their relation to Fukui indices.
AB  - A simple as well as easy to compute formalism of hardness potential (originally
      defined by Parr and Gazquez, J. Phys. Chem., 1993, 97, 3939) is presented. Use of
      hardness potential formally resolves the N-dependence problem of local hardness.
      However, the hardness potential cannot describe the intra as well as
      intermolecular reactivity sequence satisfactorily of some chemical systems. The
      corresponding electrophilic [Delta(+)h(k)] and nucleophilic [Delta(-)h(k)]
      variants of the hardness potential are also developed, which measure the
      reactivity toward a nucleophilic (i.e., Nu(-)) and an electrophilic (i.e., El(+))
      reagent, respectively. Interestingly, these two variants of the hardness
      potential lead to the right and left derivatives of Fukui potential. The proposed
      reactivity descriptors correctly predict the expected reactivity trends in the
      chosen systems. It has also been illustrated that the values of the variants of
      hardness potential (or Fukui potential) at the atomic nucleus have the ability to
      explain the intramolecular reactivity of biologically active indole derivatives.
      The future scope of applications as well as limitations of the proposed
      descriptors is also highlighted.

PMID- 23175427
TI  - Intermediate- and low-methylation epigenotypes do not correspond to CpG island
      methylator phenotype (low and -zero) in colorectal cancer.
AB  - BACKGROUND: Most recent genome-wide studies on the CpG island methylation in
      colorectal cancer (CRC) have led to the discovery of at least 3 distinct
      methylation clusters. However, there remains an uncertainty whether the CRC
      clusters identified in these studies represent compatible phenotypes. METHODS: We
      carried out comprehensive genome-scale DNA methylation profiling by Illumina
      Infinium HumanMethylation27 of 21 DNA pools that represent 84 CRC samples divided
      according to their high-, intermediate-, and low-methylation epigenotypes (HME,
      IME, and LME, respectively) and 70 normal-adjacent colonic tissues. We have also
      examined the relationship among 3 epigenotypes and chromosomal gains and
      deletions (assessed by Comparative Genomic Hybridization) in a group of 100 CRC
      samples. RESULTS: The HME subgroup showed features associated with CpG island
      methylator phenotype - high (CIMP-high) including methylation of specific CpG
      sites (CpGs) as well as significantly lower mean number of chromosomal imbalances
      when compared with other epigenotypes. The IME subgroup displayed the lowest
      number of methylated CpGs (717 vs. 2,399 and 2,679 in HME and LME, respectively)
      and highest mean number of chromosomal imbalances when compared with HME (P,
      0.001) and LME (P, 0.004). A comparison between the methylation profiles of 3
      epigenotypes revealed more similarities between the HME and LME (1,669 methylated
      CpGs overlapped) than HME and IME (673 methylated CpGs overlapped). CONCLUSION:
      Our results provide evidence that IME and LME CRCs show opposite features to
      those that have been previously attributed to CIMP-low and CIMP-0 CRCs. IMPACT:
      These discrepancies should be considered when interpreting the data from a
      particular epigenotyping method.

PMID- 23175428
TI  - Small neutral molecular carriers for selective carboxylate transport.
AB  - A series of neutral thiourea receptors were found to mediate the antiport of
      chloride with a range of biologically relevant carboxylate anions across
      phospholipid bilayers. Simple structural modification of the carriers resulted in
      a change in the lactate/pyruvate transport selectivity.

PMID- 23175429
TI  - MiR-16-1 plays a role in reducing migration and invasion of glioma cells.
AB  - MicroRNAs (miRNAs) are novel small noncoding RNA molecules that regulate gene
      expression at the post transcriptional level. Compelling evidence shows that
      there are causative links between miRNAs deregulation and cancer development and
      progression. This study aims to explore the functions of miR-16-1 on
      proliferation, apoptosis, motility, and invasion of glioma cells. Quantitative
      real-time PCR (qRT-PCR) was performed to detect the expression of miR-16-1 in
      normal brain tissues and two glioma cell lines, including U251 and U87. CCK-8,
      Annexin V/FITC (fluorescein isothiocyanate), wound healing, and transwell assays
      were used to evaluate the functions of miR-16-1 that involves cell proliferation,
      apoptosis, motility, and invasion. In addition, we conducted qRT-PCR to examine
      mRNA expression levels of Zyxin, one of putative target genes of miR-16-1, in
      U251 glioma cells after transfecting with miR-16-1 mimics. As a result, miR-16-1
      expression level was lower in U251 and U87 cells than normal brain tissues. After
      miR-16-1 was upregulated in U251 cells, cellular proliferation was notably
      attenuated but cell apoptosis was not significantly increased. Moreover,
      overexpression of miR-16-1 attenuated migration and invasion of glioma cells, and
      U251 cells transfected with miR-16-1 showed significantly lower endogenous mRNA
      levels of Zyxin than those transfected with nonspecific control miRNA or mock (P
      < 0.05). In summary, we demonstrated that miR-16-1 expression was markedly
      decreased in human glioma cell lines, and for the first time, described the roles
      of miR-16-1 in cellular proliferation, migration, and invasion abilities of high
      invasive glioma cells, and suggested that Zyxin may be one of putative target
      genes of miR-16-1.

PMID- 23175430
TI  - Evaluation of dodine, fluopyram and penthiopyrad for the management of leaf spot
      and powdery mildew of tart cherry, and fungicide sensitivity screening of
      Michigan populations of Blumeriella jaapii.
AB  - BACKGROUND: Field trials were conducted on the tart cherry cultivar Montmorency
      to evaluate the efficacy of dodine and the succinate dehydrogenase inhibitor
      (SDHI) fungicides fluopyram and penthiopyrad for control of cherry leaf spot
      (CLS) and powdery mildew (PM). The in vitro sensitivity of Blumeriella jaapii
      (CLS) to the same fungicides was also tested. RESULTS: Treatments with dodine or
      fluopyram were among the most effective for controlling CLS, while fluopyram or
      penthiopyrad treatments were among the most effective for controlling PM. In
      vitro studies detected a wide range of minimum inhibitory concentrations (MICs)
      among the isolates (0.05-400 ug AI mL(-1) ) in response to dodine. Orchard
      isolates showed reduced sensitivity to dodine as compared with baseline isolates.
      B. jaapii was more sensitive to fluopyram (0.01-10.0 ug AI mL(-1) ) than to
      penthiopyrad (0.01-25 ug AI mL(-1) ), and orchard isolates also showed a shift
      towards reduced sensitivity. CONCLUSION: The results indicate that dodine remains
      effective in CLS control. In addition, as penthiopyrad and fluopyram become
      available to growers, this research establishes baseline information that will be
      important for future monitoring and analysis of B. jaapii population responses to
      exposure to dodine and these SDHI fungicides.

PMID- 23175431
TI  - Expression of cell adhesion molecules and prognosis in breast cancer.
AB  - BACKGROUND: Cell adhesion molecules (CAMs) play an important role in the process
      of metastasis. The prognostic value of tumour expression of N-cadherin, E
      cadherin, carcinoembryonic antigen (CEA) and epithelial CAM (Ep-CAM) was
      evaluated in patients with breast cancer. METHODS: A tissue microarray of the
      patient cohort was stained immunohistochemically for all markers and analysed by
      microscopy. Expression was classified into two categories, with the median score
      as cut-off level. For CEA, the above-median category was further subdivided in
      two subgroups based on staining intensity (low or high intensity). RESULTS: The
      cohort consisted of 574 patients with breast cancer with a median follow-up of 19
      years. Below-median expression of E-cadherin (P = 0.015), and above-median
      expression of N-cadherin (P = 0.004), Ep-CAM (P = 0.046) and CEA (P = 0.001) all
      resulted in a shorter relapse-free period. Multivariable analysis revealed E
      cadherin and CEA to be independent prognostic variables. Combined analysis of CEA
      and E-cadherin expression showed a 3.6 times higher risk of relapse for patients
      with high-intensity expression of CEA, regardless of E-cadherin expression,
      compared with patients with below-median CEA and above-median E-cadherin tumour
      expression (hazard ratio 3.60, 95 per cent confidence interval 2.12 to 6.11; P <
      0.001). An interaction was found between expression of these two CAMs (P <
      0.001), suggesting a biological association. CONCLUSION: Combining E-cadherin and
      CEA tumour expression provides a prognostic parameter with high discriminative
      power that is a candidate tool for prediction of prognosis in breast cancer.

PMID- 23175432
TI  - MicroRNA-657 promotes tumorigenesis in hepatocellular carcinoma by targeting
      transducin-like enhancer protein 1 through nuclear factor kappa B pathways.
AB  - Growing evidence indicates that deregulation of microRNAs (miRNAs) contributes to
      tumorigenesis. Dysregulation of miR-657 has been observed in several types of
      cancers, but its biological function is still largely unknown. Our results showed
      that miR-657 expression can be induced by hepatitis viral proteins and is
      significantly increased in hepatocellular carcinoma (HCC) tissues. Moreover,
      introduction of miR-657 dramatically increases proliferation and colony formation
      of HCC cells in vitro and induces tumor development in immunodeficient mice.
      Further studies showed that miR-657 directly targets the transducin-like enhancer
      protein 1 (TLE1) 3' untranslated region (UTR) and activates nuclear factor kappa
      B (NF-kappaB) pathways that contribute to hepatocarcinogenesis. CONCLUSION: This
      study identified a mechanism whereby miRNA-657 contributed to HCC through novel
      cancer pathways and provides new insights into the potential molecular mechanisms
      of hepatic carcinogenesis.

PMID- 23175433
TI  - Templated assembly of Co-Pt nanoparticles via thermal and laser-induced dewetting
      of bilayer metal films.
AB  - Templated dewetting of a Co/Pt metal bilayer film on a topographic substrate was
      used to assemble arrays of Co-Pt alloy nanoparticles, with highly uniform
      particle size, shape and notably composition compared to nanoparticles formed on
      an untemplated substrate. Solid-state and liquid-state dewetting processes, using
      furnace annealing and laser irradiation respectively, were compared. Liquid state
      dewetting produced more uniform, conformal nanoparticles but they had a
      polycrystalline disordered fcc structure and relatively low magnetic coercivity.
      In contrast, solid state dewetting enabled formation of magnetically hard,
      ordered L1(0) Co-Pt single-crystal particles with coercivity >12 kOe. Furnace
      annealing converted the nanoparticles formed by liquid state dewetting into the
      L1(0) phase.

PMID- 23175434
TI  - Recent advances in laser tweezers Raman spectroscopy (LTRS) for label-free
      analysis of single cells.
AB  - Laser tweezers Raman spectroscopy (LTRS), a technique that integrates optical
      tweezers with confocal Raman spectroscopy, is a variation of micro-Raman
      spectroscopy that enables the manipulation and biochemical analysis of single
      biological particles in suspension. This article provides an overview of the LTRS
      method, with an emphasis on highlighting recent advances over the past several
      years in the development of the technology and several new biological and
      biomedical applications that have been demonstrated. A perspective on the future
      developments of this powerful cytometric technology will also be presented.

PMID- 23175436
TI  - Transdermal iontophoretic delivery of propofol: a general anaesthetic in the form
      of its phosphate salt.
AB  - The main objective of this study was to investigate the feasibility of delivery
      of propofol phosphate (PP), a prodrug of propofol, via transdermal route using
      iontophoresis in combination with chemical permeation enhancers (CPEs). PP, a
      prodrug, was synthesized and its structure was characterized. In vitro passive
      and iontophoretic drug transport studies were carried out using Franz diffusion
      cell across freshly excised hairless rat skin at different concentrations of PP
      in combination with CPE. Among all the CPEs screened, 0.1% sodium dodecyl sulfate
      (SDS) increased the passive transdermal flux to 13.43 +/- 0.73 MUg/(cm(2) h) from
      8.52 +/- 0.82 MUg/(cm(2) h) (control). Cathodal iontophoresis in combination with
      0.1% SDS synergistically enhanced the flux [249.24 +/- 6.12 MUg/(cm(2) h)] of PP.
      The Pharmacokinetic studies were performed in rat model to assess the feasibility
      of transdermal delivery of PP. The amount of propofol present in plasma samples
      in control group (passive) was below the detectable levels at all the time points
      during the study. The plasma concentration-time profile of iontophoresis group of
      rats was fit to a noncompartmental model and the pharmacokinetic parameters were
      calculated. These studies suggest the plausibility of achieving therapeutically
      relevant levels of propofol when delivered via transdermal route by combining
      iontophoresis with CPE.

PMID- 23175437
TI  - Brucine induces the apoptosis of U266 multiple myeloma cells by phosphorylation
      of c-Jun.
AB  - The aim of this study was to investigate the mechanism of the apoptotic effect of
      brucine on human multiple myeloma (MM) cells. U266 cells (5x104) were plated in
      the presence or absence of brucine (0, 0.05, 0.1, 0.2 and 0.4 mg/ml) in 96-well
      culture plates for 24-72 h. The anti-proliferative response to brucine was
      assessed by MTT assay. Analysis of the cell cycle of U266 cells treated with or
      without brucine was performed using flow cytometry. The expression change of c
      Jun following treatment with brucine or brucine plus the c-Jun N-terminal kinase
      (JNK)-specific inhibitor SP600125 was detected using RT-PCR. Brucine appeared to
      have an effect on apoptosis in a dose- and time-dependent manner. Cell cycle
      analysis using flow cytometry revealed the accumulation of cells at the sub-G0/G1
      phase. The apoptotic rates were 4.137, 10.55, 12.31, 27.67 and 29.67% (0, 0.05,
      0.1, 0.2, 0.4 mg/ml brucine, respectively; P<0.01). The gray scale values were
      0.7961 +/- 0.007 and 0.4683 +/- 0.003 (mRNA expression of c-Jun of U266 cells
      with or without SP600125, respectively). Concentrations of <= 0.4 mg/ml brucine
      induced apoptosis in U266 cells. Thus, brucine-induced apoptosis in U266 cells
      occurs via the JNK signaling pathway and phosphorylation of c-Jun.

PMID- 23175438
TI  - Handgrip strength in elderly with dementia: study of reliability.
AB  - BACKGROUND: Measuring instruments should have their scientific and clinical value
      evaluated in different populations. The handgrip strength test is widely used,
      however little has been investigated about its reliability when used in elderly
      with dementia and the right stage wich its use should be avoided. OBJECTIVES: To
      evaluate the test-retest reliability of the handgrip strength test in elderly
      with different ratings of dementia. METHOD: The cognitive function of 76 elderly
      subjects with dementia was measured, and the caregivers were interviewed to allow
      classification by the Clinical dementia rating (CDR). For these assessments the
      Mini-Metal State Examination and the Pfeffer, Lawton, and Katz scales were used.
      Twenty subjects were classified as borderline (83.4+/-5.8 years), 19 as mild
      (82.4+/-6.8 years), 19 as moderate (85.8+/-5.6 years) and 18 as severe dementia
      (84.0+/-5.1 years). Handgrip strength was assessed with a JAMAR hydraulic
      dynamometer and after one week it was reevaluated. Reliability was analyzed by
      Intraclass Correlation Coefficient (ICC). The significance level was set at
      alpha=0.05. RESULTS: Test-retest reliability was excellent for groups with
      borderline (ICC=0.975; p=0.001), mild (ICC=0.968; p=0.002), and moderate
      (ICC=0.964; p=0.001) dementia. The analysis of the group with a severe CDR showed
      no statistical significance and a low ICC (ICC=0.415; p=0.376). CONCLUSION: The
      handgrip strength test has excellent reliability when used in elderly with
      borderline, mild, and moderate dementia, which enables its use in research.
      However, its use is not recommended in elderly classified with severe dementia
      due to the measure's low reliability and subsequent irrelevance in clinical
      practice.

PMID- 23175439
TI  - Profile of the elderly in physical therapy and its relation to functional
      disability.
AB  - BACKGROUND: As the population ages, changes occur in the epidemiological profile
      towards the current predominance of chronic degenerative diseases which, when
      untreated, lead to loss of functional capacity and require long-term assistance.
      OBJECTIVES: To describe the profile of the elderly attending the geriatric
      physical therapy service and to identify factors associated with functional
      disability. METHOD: A cross-sectional descriptive analytical study was conducted.
      The medical records of elderly individuals were analyzed using the first physical
      therapy assessment, which included sociodemographic, clinical and mobility data.
      To determine the degree of disability (mild/moderate), the Brazilian
      Multidimensional Functional Assessment Questionnaire (BOMFAQ) was used.
      Descriptive analysis and univariate logistic regression were performed, followed
      by multivariate logistic regression. RESULTS: The sample comprised 130 elderly
      patients with a mean age of 73.3 [standar deviation (SD)=7.2] years-old,
      predominantly female (63.9%), sedentary (71.5%) and presenting three to four
      diseases (47.7%). The mean of activities with difficulty in the BOMFAQ was 6.7
      (SD=4.8), 35 (26.9%) individuals presented mild disability and 95 (73.1%)
      moderate. The participant characteristic that presented a greatest risk of
      disability was self-reporting of poor health (OR=12.4). The factors identified,
      which together can determine functional decline, were sedentary lifestyle,
      presence of dizziness, polypharmacy and high pain intensity. CONCLUSIONS: Elderly
      individuals attended by the geriatric physical therapy service showed a profile
      associated with disability, characterized by potentially modifiable factors. This
      profile also reinforces the demand for long-term care for this population.

PMID- 23175440
TI  - COPI transport complexes bind to specific RNAs in neuronal cells.
AB  - Our fundamental understanding of how several thousand diverse RNAs are recognized
      in the soma, sorted, packaged, transported and localized within the cell is
      fragmentary. The COPa and COPb proteins of the coatomer protein I (COPI) vesicle
      complex were reported to interact with specific RNAs and represent a candidate
      RNA sorting and transport system. To determine the RNA-binding profile of Golgi
      derived COPI in neuronal cells, we performed formaldehyde-linked RNA
      immunoprecipitation, followed by high-throughput sequencing, a process we term
      FLRIP-Seq (FLRIP, formaldehyde-cross-linked immunoprecipitation). We demonstrate
      that COPa co-immunoprecipitates a specific set of RNAs that are enriched in G
      quadruplex motifs and fragile X mental retardation protein-associated RNAs and
      that encode factors that predominantly localize to the plasma membrane and
      cytoskeleton and function within signaling pathways. These data support the novel
      function of COPI in inter-compartmental trafficking of RNA.

PMID- 23175441
TI  - Epigenome-wide association study in the European Prospective Investigation into
      Cancer and Nutrition (EPIC-Turin) identifies novel genetic loci associated with
      smoking.
AB  - A single cytosine-guanine dinucleotide (CpG) site within coagulation factor II
      (thrombin) receptor-like 3 (F2RL3) was recently found to be hypomethylated in
      peripheral blood genomic DNA from smokers compared with former and non-smokers.
      We performed two epigenome-wide association studies (EWAS) nested in a
      prospective healthy cohort using the Illumina 450K Methylation Beadchip. The two
      populations consisted of matched pairs of healthy individuals (n = 374), of which
      half went on to develop breast or colon cancer. The association was analysed
      between methylation and smoking status, as well as cancer risk. In addition to
      the same locus in F2RL3, we report several loci that are hypomethylated in
      smokers compared with former and non-smokers, including an intragenic region of
      the aryl hydrocarbon receptor repressor gene (AHRR; cg05575921, P = 2.31 * 10(
      15); effect size = 14-17%), an intergenic CpG island on 2q37.1 (cg21566642, P =
      3.73 * 10(-13); effect size = 12%) and a further intergenic region at 6p21.33
      (cg06126421, P = 4.96 * 10(-11), effect size = 7-8%). Bisulphite pyrosequencing
      validated six loci in a further independent population of healthy individuals (n
      = 180). Methylation levels in AHRR were also significantly decreased (P < 0.001)
      and expression increased (P = 0.0047) in the lung tissue of current smokers
      compared with non-smokers. This was further validated in a mouse model of smoke
      exposure. We observed an association with breast cancer risk for the 2q37.1 locus
      (P = 0.003, adjusted for the smoking status), but not for the other loci
      associated with smoking. These data show that smoking has a direct effect on the
      epigenome in lung tissue, which is also detectable in peripheral blood DNA and
      may contribute to cancer risk.

PMID- 23175442
TI  - Hippocampal dysfunction in the Euchromatin histone methyltransferase 1
      heterozygous knockout mouse model for Kleefstra syndrome.
AB  - Euchromatin histone methyltransferase 1 (EHMT1) is a highly conserved protein
      that catalyzes mono- and dimethylation of histone H3 lysine 9, thereby
      epigenetically regulating transcription. Kleefstra syndrome (KS), is caused by
      haploinsufficiency of the EHMT1 gene, and is an example of an emerging group of
      intellectual disability (ID) disorders caused by genes encoding epigenetic
      regulators of neuronal gene activity. Little is known about the mechanisms
      underlying this disorder, prompting us to study the Euchromatin histone
      methyltransferase 1 heterozygous knockout (Ehmt1(+/-)) mice as a model for KS. In
      agreement with the cognitive disturbances observed in patients with KS, we
      detected deficits in fear extinction learning and both novel and spatial object
      recognition in Ehmt1(+/-) mice. These learning and memory deficits were
      associated with a significant reduction in dendritic arborization and the number
      of mature spines in hippocampal CA1 pyramidal neurons of Ehmt1(+/-) mice. In
      depth analysis of the electrophysiological properties of CA3-CA1 synapses
      revealed no differences in basal synaptic transmission or theta-burst induced
      long-term potentiation (LTP). However, paired-pulse facilitation (PPF) was
      significantly increased in Ehmt1(+/-) neurons, pointing to a potential deficiency
      in presynaptic neurotransmitter release. Accordingly, a reduction in the
      frequency of miniature excitatory post-synaptic currents (mEPSCs) was observed in
      Ehmt1(+/-) neurons. These data demonstrate that Ehmt1 haploinsufficiency in mice
      leads to learning deficits and synaptic dysfunction, providing a possible
      mechanism for the ID phenotype in patients with KS.

PMID- 23175443
TI  - Oncogenic FGFR3 gene fusions in bladder cancer.
AB  - FGF receptor 3 (FGFR3) is activated by mutation or over-expression in many
      bladder cancers. Here, we identify an additional mechanism of activation via
      chromosomal re-arrangement to generate constitutively activated fusion genes.
      FGFR3-transforming acid coiled coil 3 (TACC3) fusions resulting from 4p16.3 re
      arrangements and a t(4;7) that generates a FGFR3-BAI1-associated protein 2-like 1
      (BAIAP2L1) fusion were identified in 4 of 43 bladder tumour cell lines and 2 of
      32 selected tissue samples including the tumour from which one of the cell lines
      was derived. These are highly activated and transform NIH-3T3 cells. The FGFR3
      component is identical in all cases and lacks the final exon that includes the
      phospholipase C gamma 1 (PLCgamma1) binding site. Expression of the fusions in
      immortalized normal human urothelial cells (NHUC) induced activation of the
      mitogen-activated protein kinase pathway but not PLCgamma1. A protein with loss
      of the terminal region alone was not as highly activated as the fusion proteins,
      indicating that the fusion partners are essential. The TACC3 fusions retain the
      TACC domain that mediates microtubule binding and the BAIAP2L1 fusion retains the
      IRSp53/MIM domain (IMD) that mediates actin binding and Rac interaction. As
      urothelial cell lines with FGFR3 fusions are extremely sensitive to FGFR
      selective agents, the presence of a fusion gene may aid in selection of patients
      for FGFR-targeted therapy.

PMID- 23175444
TI  - Yeast model for evaluating the pathogenic significance of SDHB, SDHC and SDHD
      mutations in PHEO-PGL syndrome.
AB  - SDH genes, encoding succinate dehydrogenase, act as tumour suppressor genes,
      linking mitochondrial dysfunction with tumourigenesis. Heterozygous germline
      mutations in SDHA, SDHB, SDHC, SDHD and in the assembly factor encoding gene
      SDHAF2 have all been shown to predispose to heritable endocrine neoplasias such
      as pheochromocytomas (PHEO) and paragangliomas (PGLs) called 'PHEO-PGL syndrome'.
      SDH genes mutations, in addition to deletions or truncations which are most
      likely pathogenic, often include missense substitutions which can be of uncertain
      significance. Unclassified missense substitutions may be difficult to interpret
      unless the cause-effect link between mutation and the disease is established by
      functional and in silico studies or by the familial segregation with the
      phenotype. Using the yeast model, here, we report functional investigations on
      several missense SDH mutations found in patients affected by pheochromocytomas or
      paragangliomas. The aim of this study was to evaluate whether and to which extent
      the yeast model may be useful for establishing the pathological significance of
      missense SDH mutations in humans. The results of our study demonstrate that the
      yeast is a good functional model to validate the pathogenic significance of SDHB
      missense mutations while, for missense mutations in SDHC and SDHD genes, the
      model can be informative only when the variation involves a conserved residue in
      a conserved domain.

PMID- 23175446
TI  - Ab initio calculations of the Ar-ethane intermolecular potential energy surface
      using bond function basis sets.
AB  - The intermolecular potential energy surface (PES) of argon with ethane has been
      studied by ab initio calculations at the levels of second-order Moller-Plesset
      perturbation (MP2) theory and coupled-cluster theory with single, double, and
      noniterative triple configurations (CCSD(T)) using a series of augmented
      correlation-consistent basis sets. Two sets of bond functions, bf1 (3s3p2d) and
      bf2 (6s6p4d2f), have been added to the basis sets to show a dramatic and
      systematic improvement in the convergence of the entire PES. The PES of Ar-ethane
      is characterized by a global minimum at a near T-shaped configuration with a well
      depth of 0.611 kcal mol(-1), a second minimum at a collinear configuration with a
      well depth of 0.456 kcal mol(-1), and a saddle point connecting the two minima.
      It is shown that an augmented correlation-consistent basis set with a set of bond
      functions, either bf1 or bf2, can effectively produce results equivalent to the
      next larger augmented correlation-consistent basis set, that is, aug-cc-pVDZ-bf1
      ~ aug-cc-pVTZ, aug-cc-pVTZ-bf1 ~ aug-cc-pVQZ. Very importantly, the use of bond
      functions improves the PES globally, resulting accurate potential anisotropy.
      Finally, MP2 method is inadequate for accurate calculations, because it gives a
      potentially overestimated well depth and, more seriously, a poor potential
      anisotropy.

PMID- 23175445
TI  - Noncanonical microRNAs and endogenous siRNAs in normal and psoriatic human skin.
AB  - Noncanonical microRNAs (miRNAs) and endogenous small interfering RNAs (endo
      siRNAs) are key gene regulators in eukaryotes. Noncanonical miRNAs, which bypass
      part of the canonical miRNA biogenesis pathway, can originate from a variety of
      genomic loci, which include small nucleolar RNAs (snoRNAs), transfer RNAs (tRNAs)
      and introns, whereas endo-siRNAs can arise from repetitive elements, some of
      which are transposable. The roles of noncanonical miRNAs and endo-siRNAs in
      complex diseases have yet to be characterized. To investigate their potential
      expression and function in psoriasis, we carried out a comprehensive, genome-wide
      search for noncanonical miRNAs and endo-siRNAs in small RNA deep-sequencing data
      sets from normal and psoriatic human skin. By analyzing more than 670 million
      qualified reads from 67 small RNA libraries, we identified 21 novel, noncanonical
      miRNAs (3 snoRNA-derived and 2 tRNA-derived miRNAs and 16 miRtrons) and 39 novel
      endo-siRNAs that were expressed in skin. The expression of four novel small RNAs
      was validated by qRT-PCR in human skin, and their Argonaute association was
      confirmed by co-immunoprecipitation of ectopic small RNAs in HEK293 cells.
      Fifteen noncanonical miRNAs or endo-siRNAs were significantly differentially
      expressed in psoriatic-involved versus normal skin, including an Alu-short
      interspersed element-derived siRNA which was 17-fold up-regulated in psoriatic
      involved skin. These and other differentially expressed small noncoding RNAs may
      function as regulators of gene expression in skin and potentially play a role in
      psoriasis pathogenesis.

PMID- 23175447
TI  - Identification and quantification of atractylenolide I and atractylenolide III in
      Rhizoma Atractylodes Macrocephala by liquid chromatography-ion trap mass
      spectrometry.
AB  - Rhizoma Atractylodes Macrocephala (RAM) is an important traditional Chinese
      medicinal herb that is used for treatment of dyspepsia and anorexia. The active
      ingredients, atractylenolide I (AO-I) and atractylenolide III (AO-III), were
      identified by direct-injection ion trap-mass spectrometry (IT-MS) for collecting
      MS(n) spectra. The major fragment ions of AO-I and AO-III were confirmed by MS(n)
      both in negative ion mode and in positive ion mode. The possible main cleavage
      pathway of fragment ions was studied. The determinations of AO-I and AO-III were
      accomplished by liquid chromatography (LC) with UV and MS. The analytes provided
      good signals corresponding to the protonated molecular ions [M + H](+) and
      product ions. The precursor ions and product ions for quantification of AO-III
      and AO-I were m/z 249 -> 231 and m/z 233 -> 215, respectively, using selected ion
      monitoring by LC-IT-MS. Two methods were evaluated for a number of validation
      characteristics (repeatability, limit of detection, calibration range, and
      recovery). MS provides a high selectivity and sensitivity for determination of AO
      III and AO-I in positive mode. After optimization of the methods, separation,
      identification and quantification of the two components in RAM were
      comprehensively tested by HPLC with UV and MS.

PMID- 23175448
TI  - BRCA1 germ-line mutations and tumor characteristics in eastern Chinese women with
      familial breast cancer.
AB  - Although several studies detected the BRCA1 germ-line mutations in Chinese women
      with familial breast cancer, most of them did not employ conventional full gene
      sequencing, especially in eastern China. In addition, the clinicopathological
      features of BRCA1-associated breast cancer in Chinese women were not well
      investigated. In this study, we screened the complete coding regions and exon
      intron boundaries of BRCA1 by polymerase chain reaction (PCR)-sequencing assay.
      Immunohistochemistry analyses were performed on tumor samples to detect the
      expression of estrogen receptor (ER), progesterone receptor (PR), P53, and human
      epidermal growth factor receptor-2 (HER-2). Breast cancer patients having one or
      more affected relatives referred from the Zhejiang Cancer Hospital, eastern China
      during 2008-2011 were selected for the study. A total of 62 familial breast
      cancer patients received the BRCA1 germ-line mutation screening. Five deleterious
      mutations were detected in this cohort. The mutation rate was 11.3% (7/62). We
      found two novel mutations (3414delC and 5,280 C > T) and two recurrent mutations
      (5,273 G > A and 5589del8). BRCA1 mutation tumors tended to be negative for ER,
      PR, and HER-2, and exhibited high histological grade compared with tumors without
      BRCA1 mutations. Our study suggests that recurrent mutations may exist in eastern
      Chinese women with familial breast cancer and PCR-sequencing assay is a useful
      tool to screen these mutations. It also suggests that BRCA1-associated breast
      cancers in Chinese women exhibit an aggressive phenotype.

PMID- 23175449
TI  - Neurophilin-1 in tumor growth.

PMID- 23175450
TI  - Efficacy vs. effectiveness: erlotinib in previously treated non-small-cell lung
      cancer.
AB  - BACKGROUND: A randomized trial carried out by Shepherd et al. in patients with
      advanced or metastatic non-small-cell lung cancer showed statistically
      significant benefit of erlotinib over placebo in prolonging overall survival and
      progression-free survival. OBJECTIVES: The primary outcome was to compare overall
      survival of patients treated with erlotinib for non-small-cell lung cancer at
      Alberta Health Services - Cancer Care to the overall survival seen in the pivotal
      trial. Secondary outcomes included comparing progression-free survival, overall
      response rate, and duration of response between the two patient populations.
      METHODS: A retrospective review of charts was conducted for patients with locally
      advanced or metastatic non-small-cell lung cancer who received erlotinib therapy
      after failure of at least one prior chemotherapy regimen between 1 August 2006
      and 31 July 2009. Survival data was analyzed using the Kaplan-Meier method.
      RESULTS: Median overall survival and progression-free survival were 5.19 months
      and 2.46 months, respectively, in Alberta Health Services - Cancer Care patients.
      The rate of response was 11% (median duration of response, 6.7 months). The
      likelihood of a response to erlotinib was higher among nonsmokers (p < 0.0001)
      and those with response to prior chemotherapy (p = 0.0896). In multivariate
      analysis, good performance status (p = 0.0109) and response to prior therapy (p <
      0.0001) were favorable factors for survival. CONCLUSIONS: In a clinical setting,
      erlotinib does not perform as well in terms of median overall survival as
      reported in the pivotal trial (5.19 vs. 6.70 months).

PMID- 23175451
TI  - Comparing clinicians' use of an anticoagulation management service and usual care
      in ambulatory oncology.
AB  - PURPOSE: There is no consensus in the oncology community about the optimal model
      for anticoagulation management of ambulatory cancer patients. To understand
      oncologists' preferences regarding anticoagulation management, we compared the
      characteristics of patients referred to an oncology-oriented anticoagulation
      management service with "usual care" patients managed by the patient's primary
      oncologist. METHODS: We performed a retrospective medical record review of
      ambulatory oncology patients' anticoagulation care at a comprehensive cancer
      center. We examined the characteristics of 33 patients anticoagulated before
      implementation of a dedicated oncology anticoagulation management service. We
      compared this group with 33 patients managed by the anticoagulation management
      service and with 39 usual care patients managed by the primary oncologist after
      the anticoagulation management service was created. We also examined differences
      in laboratory test utilization, time in the therapeutic range (for patients
      anticoagulated with warfarin), and anticoagulation-related adverse events during
      a 3-month assessment period. RESULTS: Anticoagulation management service patients
      were more likely to be treated for hematologic malignancies, use erythropoietin
      stimulating agents, and require warfarin management for previous venous
      thromboembolic disease compared to usual care patients. In contrast, oncologists
      were more likely to manage anticoagulation care of patients with advanced solid
      tumors undergoing active chemotherapy. Anticoagulation management service and
      usual care patients on warfarin therapy had comparable time in the therapeutic
      range and complication rates. CONCLUSION: Oncologists selectively referred
      patients to the anticoagulation management service. Anticoagulation management
      service patients' warfarin control and complication rates were comparable to care
      provided by the primary oncologist, suggesting that an oncology-specific
      anticoagulation management service may be a feasible and effective option for
      anticoagulation management of ambulatory oncology patients.

PMID- 23175452
TI  - A versatile approach for decorating 2D nanomaterials with Pd or Pt nanoparticles.
AB  - Bubbling H(2) into colloidal suspensions of 2D sheets of graphene or h-BN
      stabilised in water with p-phosphonic acid calix[8]arene, and pre-treated to bind
      Pd(II) or Pt(IV) species to their surfaces, is effective in decorating the
      material with nanoparticles of the noble metals approximately 5 nm in diameter.

PMID- 23175453
TI  - The structure of plutonium(IV) oxide as hydrolysed clusters in aqueous
      suspensions.
AB  - The behavior of plutonium still puzzles scientists 70 years after its discovery.
      There are several factors making the chemistry of plutonium interesting including
      its ability to keep several oxidation states. Another unique property is that the
      oxidation states +III, +IV, +V and +VI may exist simultaneously in solution.
      Another property plutonium shares with some other tetravalent metal ions is the
      ability to form stable polynuclear complexes or colloids. The structures of
      freshly prepared and five-year old plutonium(IV) colloids are compared with
      crystalline plutonium(IV) oxide using Pu L(3)-edge EXAFS. It was shown that as
      the plutonium colloids age they do in fact shrink in size, contrary to previous
      expectations. The aged colloidal particles are indeed very small with only 3-4
      plutonium atoms, and with a structure very similar to solid plutonium(IV) oxide,
      but with somewhat shorter mean Pu-O bond and Pu...Pu distances indicating a
      partial oxidation. The very small size of the colloidal particles is further
      supported by the fact that they do not sediment on heavy ultra-centrifugation.

PMID- 23175454
TI  - Causal contributions of the left frontal eye field to conscious perception.
AB  - The quest for the neural correlates of consciousness has led to controversial
      results. When contrasting consciously seen versus unseen stimuli, some authors
      have proposed that consciousness is related to activity in visual areas along the
      ventral cortical visual stream, while others propose the implication of parietal
      and frontal regions ( Dehaene and Changeux 2011). When invisibility is caused by
      neglect or inattention, high levels of activity recorded in early visual areas (
      Vuilleumier et al. 2001) suggest that further activity in fronto-parietal regions
      might be necessary for conscious perception. Recent functional magnetic resonance
      imaging evidence ( Chica, Paz-Alonso, et al. 2012) suggested a key role for the
      left frontal eye field (FEF) in the attentional modulation of visual
      consciousness. Here, we used the high temporal resolution and causal power of
      event-related transcranial magnetic stimulation to explore the causal
      contributions of the left FEF on conscious perception and to assess whether or
      not these effects are mediated by the orienting of spatial attention. Our results
      provide the first causal evidence on the contribution of the left FEF to
      conscious visual perception and indicate that such effects are likely to be
      mediated by its known role on attentional orienting. 

PMID- 23175455
TI  - Pesticide hazard trends in orchard fruit production in Great Britain from 1992 to
      2008: a time-series analysis.
AB  - BACKGROUND: Attempts to mitigate pesticide hazard in horticulture present policy
      makers and industry with complex challenges at both the national and European
      scale. The impact of policy initiatives and industry practice on reducing hazard
      is contingent upon effective monitoring of a broad spectrum of non-target
      endpoints. This study used the environmental impact quotient to evaluate changes
      in orchard fruit pesticide hazard in Great Britain. The study period corresponded
      to the introduction of European Directive 91/414 in 1991 and extended to 2008,
      the last pesticide survey year prior to the implementation of the new European
      Directive 2009/128/EC and regulation (EC) No. 1107/2009. RESULTS: Overall,
      pesticide hazard declined for each of the measures reported, with the
      environmental impact per hectare per tonne of produce declining by -21%.
      CONCLUSION: The UK orchard fruit industry appears to have improved efficiencies
      in pesticide use and is now harvesting more produce per hectare while
      simultaneously reducing the associated environmental impact of pesticides. The
      removal of toxic substances and their replacement with more benign products as a
      consequence of legislation appears to have played an important role in
      facilitating the reduction.

PMID- 23175456
TI  - Reduction of depressive symptoms in an elderly Mexican-American female with type
      2 diabetes mellitus: a single-subject study.
AB  - The purpose of this study was to determine if occupation-based activities improve
      diabetes self-management and reduce depressive symptoms in an elderly Mexican
      American woman with type 2 diabetes mellitus (T2DM). There have been no known
      studies showing occupational therapy's role in self-care management of T2DM in
      people with depressive symptoms. The individual in this single-subject research
      was evaluated using glycosylated haemoglobin blood tests, four self-reported
      standardized questionnaires, participant reflective logs and clinical
      observations following an 8-week intervention. The participant improved on all
      measures, which were sustained 1 month after treatment ended. Clinical
      implications highlight a new role for occupational therapists providing early
      intervention in people with diabetes and depression for secondary prevention of
      complications of uncontrolled diabetes. Research suggestions include multiple
      single-subject studies showing occupational therapy contributions.

PMID- 23175458
TI  - An efficient method for computing the QTAIM topology of a scalar field: the
      electron density case.
AB  - An efficient method for computing the quantum theory of atoms in molecules
      (QTAIM) topology of the electron density (or other scalar field) is presented. A
      modified Newton-Raphson algorithm was implemented for finding the critical points
      (CP) of the electron density. Bond paths were constructed with the second-order
      Runge-Kutta method. Vectorization of the present algorithm makes it to scale
      linearly with the system size. The parallel efficiency decreases with the number
      of processors (from 70% to 50%) with an average of 54%. The accuracy and
      performance of the method are demonstrated by computing the QTAIM topology of the
      electron density of a series of representative molecules. Our results show that
      our algorithm might allow to apply QTAIM analysis to large systems (carbon
      nanotubes, polymers, fullerenes) considered unreachable until now.

PMID- 23175457
TI  - Sexual transmission of hepatitis C virus among monogamous heterosexual couples:
      the HCV partners study.
AB  - The efficiency of hepatitis C virus (HCV) transmission by sexual activity remains
      controversial. We conducted a cross-sectional study of HCV-positive subjects and
      their partners to estimate the risk for HCV infection among monogamous
      heterosexual couples. A total of 500 anti-HCV-positive, human immunodeficiency
      virus-negative index subjects and their long-term heterosexual partners were
      studied. Couples were interviewed separately for lifetime risk factors for HCV
      infection, within-couple sexual practices, and sharing of personal grooming
      items. Blood samples were tested for anti-HCV, HCV RNA, and HCV genotype and
      serotype. Sequencing and phylogenetic analysis determined the relatedness of
      virus isolates among genotype-concordant couples. The majority of HCV-positive
      index subjects were non-Hispanic white, with a median age of 49 years (range, 26
      79 years) and median of 15 years (range, 2-52 years) of sexual activity with
      their partners. Overall, HCV prevalence among partners was 4% (n=20), and nine
      couples had concordant genotype/serotype. Viral isolates in three couples (0.6%)
      were highly related, consistent with transmission of virus within the couple.
      Based on 8,377 person-years of follow-up, the maximum incidence rate of HCV
      transmission by sex was 0.07% per year (95% confidence interval, 0.01-0.13) or
      approximately one per 190,000 sexual contacts. No specific sexual practices were
      related to HCV positivity among couples. CONCLUSION: The results of this study
      provide quantifiable risk information for counseling long-term monogamous
      heterosexual couples in which one partner has chronic HCV infection. In addition
      to the extremely low estimated risk for HCV infection in sexual partners, the
      lack of association with specific sexual practices provides unambiguous and
      reassuring counseling messages.

PMID- 23175459
TI  - Ethics of medical care and clinical research: a qualitative study of principal
      investigators in biomedical HIV prevention research.
AB  - In clinical research there is a tension between the role of a doctor, who must
      serve the best interests of the patient, and the role of the researcher, who must
      produce knowledge that may not have any immediate benefits for the research
      participant. This tension is exacerbated in HIV research in low and middle income
      countries, which frequently uncovers comorbidities other than the condition under
      study. Some bioethicists argue that as the goals of medicine and those of
      research are distinct, it is a mistake for researchers to assume therapeutic
      responsibilities while engaging in research. Others propose that there is a duty
      of care, but disagree as to how this is limited and specified. In this
      qualitative study, principal investigators from HIV prevention trials discuss
      their experience of providing medical benefits to participants within the context
      of conducting research into HIV biomedical prevention technologies. They describe
      the limitations imposed at times by funders and at times by infrastructure
      constraints, and canvass the importance of ancillary care provision and capacity
      building in trial communities. The views of the principal investigators are
      compatible with the perspective that there is a duty of care, limited by the
      nature of the research, the depth of the relationship between research and
      participant, and the capacity of the research site. The therapeutic orientation
      in HIV prevention trial appears to be indivisible from competent research
      practise by making concrete and appropriate benefits available to trial
      participants and their communities that support rather than compete with local
      infrastructure.

PMID- 23175460
TI  - Can phase I cancer research studies in children be justified on ethical grounds?

PMID- 23175461
TI  - Raman spectroscopy coupled with advanced statistics for differentiating menstrual
      and peripheral blood.
AB  - Body fluids are a common and important type of forensic evidence. In particular,
      the identification of menstrual blood stains is often a key step during the
      investigation of rape cases. Here, we report on the application of near-infrared
      Raman microspectroscopy for differentiating menstrual blood from peripheral
      blood. We observed that the menstrual and peripheral blood samples have similar
      but distinct Raman spectra. Advanced statistical analysis of the multiple Raman
      spectra that were automatically (Raman mapping) acquired from the 40 dried blood
      stains (20 donors for each group) allowed us to build classification model with
      maximum (100%) sensitivity and specificity. We also demonstrated that despite
      certain common constituents, menstrual blood can be readily distinguished from
      vaginal fluid. All of the classification models were verified using cross
      validation methods. The proposed method overcomes the problems associated with
      currently used biochemical methods, which are destructive, time consuming and
      expensive.

PMID- 23175462
TI  - Nanomedicines and nanodiagnostics come of age.
AB  - Although the employment of biomedical colloids is not new, modern biomedical
      colloids, termed nanomedicines and nanodiagnostics, have enhanced functionality,
      in that the drug compound/diagnostic probe entrapped within the nanoparticle
      takes on the properties of the encapsulating nanoparticle. The nanoparticle's
      properties are specifically dictated by its size, shape, and surface chemistry;
      the net result in the case of medicines is an alteration of the drug's intrinsic
      pharmacokinetics and eventual drug targeting to the areas of pathology. The first
      nanomedicines, which really altered the pharmacokinetics of a drug molecule, were
      licensed in the early-to-mid 1990s. Since this time, these pioneering
      nanomedicines: liposomal doxorubicin (Doxil) and liposomal amphotericin B
      (Ambisome), have been followed by medicines such as albumin-stabilised paclitaxel
      (Abraxane) and biomedical sentinel lymph node nanodiagnostics such as Sienna+.
      The clinical trials database is heavily populated with nanosystem trials--an
      indication that these agents are growing in stature and will be utilised in an
      expanding list of clinical situations. Although the intravenous route is the
      route of choice for the current nanoparticles, new administration routes such as
      the pulmonary route are already in clinical testing, and researchers are working
      on the preclinical development of oral nanomedicines.

PMID- 23175464
TI  - Toll-like receptor 2: therapeutic target for gastric carcinogenesis.

PMID- 23175463
TI  - Placental stem cell correction of murine intermediate maple syrup urine disease.
AB  - There is improved survival and partial metabolic correction of a mouse
      intermediate maple syrup urine disease (iMSUD) model after allogenic hepatocyte
      transplantation, confirming that a small number of enzyme-proficient liver
      engrafted cells can improve phenotype. However, clinical shortages of suitable
      livers for hepatocyte isolation indicate a need for alternative cell sources.
      Human amnion epithelial cells (hAECs) share stem cell characteristics without the
      latter's safety and ethical concerns and differentiate to hepatocyte-like cells.
      Eight direct hepatic hAEC transplantations were performed in iMSUD mice over the
      first 35 days beginning at birth; animals were provided a normal protein diet and
      sacrificed at 35 and 100 days. Treatment at the neonatal stage is clinically
      relevant for MSUD and may offer a donor cell engraftment advantage. Survival was
      significantly extended and body weight was normalized in iMSUD mice receiving
      hAEC transplantations compared with untreated iMSUD mice, which were severely
      cachectic and died <=28 days after birth. Branched chain alpha-keto acid
      dehydrogenase enzyme activity was significantly increased in transplanted livers.
      The branched chain amino acids leucine, isoleucine, valine, and alloisoleucine
      were significantly improved in serum and brain, as were other large neutral amino
      acids. CONCLUSION: Placental-derived stem cell transplantation lengthened
      survival and corrected many amino acid imbalances in a mouse model of iMSUD. This
      highlights the potential for their use as a viable alternative clinical therapy
      for MSUD and other liver-based metabolic diseases.

PMID- 23175465
TI  - Life course effects on age at menopause among Bangladeshi sedentees and migrants
      to the UK.
AB  - OBJECTIVES: To assess how different variables experienced across the life course,
      but particularly during early life, might affect age at menopause among 174
      Bangladeshi migrants to London by comparing them to 157 nonmigrant sedentees and
      154 women of European descent in London. METHODS: Participants were aged 35-59
      years, with no exogenous hormone use in the past three months, not pregnant or
      lactating, with no history of hysterectomy or oophorectomy. Face-to-face
      interviews and anthropometric measures were carried out. In addition to mean
      recalled age at natural menopause, median age was computed by probit analysis.
      Ages at menopause were examined by bivariate and Cox regression analyses in
      relation to demographic, reproductive, and lifestyle variables, and in relation
      to potential exposure to cyclones in early childhood. RESULTS: Ages at menopause
      were significantly earlier among Bangladeshi sedentees and immigrants compared to
      Londoners of European origin. Ages at menopause were earlier among sedentees
      compared to immigrants. Urban birthplace, more infectious diseases during
      childhood, and lower levels of education increased the risk of an earlier
      menopause. CONCLUSIONS: Changes in environmental conditions during adulthood
      appeared to modify age at menopause among Bangladeshi immigrants in London
      compared to women living in Bangladesh; however, Bangladeshi immigrants still
      experienced an earlier age at menopause compared with their London neighbors of
      European descent.

PMID- 23175466
TI  - Constitutive Notch2 signaling induces hepatic tumors in mice.
AB  - Hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCC) are the most common
      liver tumors and a leading cause for cancer-related death in men. Notch2
      regulates cellular differentiation in the developing and adult liver. Although
      aberrant Notch signaling is implicated in various cancers, it is still unclear
      whether Notch2 regulates proliferation and differentiation in liver
      carcinogenesis and thereby contributes to HCC and CCC formation. Here, we
      investigated the oncogenic potential of constitutive Notch2 signaling in the
      liver. We show that liver-specific expression of the intracellular domain of
      Notch2 (N2ICD) in mice is sufficient to induce HCC formation and biliary
      hyperplasia. Specifically, constitutive N2ICD signaling in the liver leads to up
      regulation of pro-proliferative genes and proliferation of hepatocytes and
      biliary epithelial cells (BECs). Using the diethylnitrosamine (DEN) HCC
      carcinogenesis model, we further show that constitutive Notch2 signaling
      accelerates DEN-induced HCC formation. DEN-induced HCCs with constitutive Notch2
      signaling (DEN(N2ICD) HCCs) exhibit a marked increase in size, proliferation, and
      expression of pro-proliferative genes when compared with HCCs from DEN-induced
      control mice (DEN(ctrl) HCCs). Moreover, DEN(N2ICD) HCCs exhibit increased Sox9
      messenger RNA (mRNA) levels and reduced Albumin and Alpha-fetoprotein mRNA
      levels, indicating that they are less differentiated than DEN(ctrl) HCCs.
      Additionally, DEN(N2ICD) mice develop large hepatic cysts, dysplasia of the
      biliary epithelium, and eventually CCC. CCC formation in patients and DEN(N2ICD)
      mice is accompanied by re-expression of hepatocyte nuclear factor
      4alpha(HNF4alpha), possibly indicating dedifferentiation of BECs. CONCLUSION: Our
      data establish an oncogenic role for constitutive Notch2 signaling in liver
      cancer development.

PMID- 23175468
TI  - Complexes of 4-substituted phenolates with HF and HCN: energy decomposition and
      electronic structure analyses of hydrogen bonding.
AB  - We have computationally studied para-X-substituted phenols and phenolates (X =
      NO, NO(2), CHO, COMe, COOH, CONH(2), Cl, F, H, Me, OMe, and OH) and their
      hydrogen-bonded complexes with B(-) and HB (B = F and CN), respectively, at
      B3LYP/6-311++G** and BLYP-D/QZ4P levels of theory. Our purpose is to explore the
      structures and stabilities of these complexes. Moreover, to understand the
      emerging trends, we have analyzed the bonding mechanisms using the natural bond
      orbital scheme as well as Kohn-Sham molecular orbital (MO) theory in combination
      with quantitative energy decomposition analyses [energy decomposition analysis
      (EDA), extended transition state-natural orbitals for chemical valence (ETS
      NOCV)]. These quantitative analyses allow for the construction of a simple
      physical model that explains all computational observations.

PMID- 23175467
TI  - Pyramiding and evaluation of three dominant brown planthopper resistance genes in
      the elite indica rice 9311 and its hybrids.
AB  - BACKGROUND: Brown planthopper (BPH), Nilaparvata lugens Stal, is the most
      devastating insect pest in rice-producing areas. Three dominant BPH resistance
      genes (Bph14, Bph15, Bph18) were pyramided into elite indica rice 9311 and its
      hybrids using marker-assisted selection. Gene effectiveness was evaluated on the
      basis of seedling and adult rice resistance, honeydew weight and survival rate of
      BPH. RESULTS: All three genes affected BPH growth and development and antibiotic
      factors, resulting in both seedling and adult resistance. Bph15 had the greatest
      effect on conferring resistance to BPH. The results showed an additive effect of
      pyramiding genes, the order of the gene effect being 14/15/18 >= 14/15 > 15/18 >=
      15 > 14/18 >= 14 >= 18 > none. The pyramided or single-gene introgression hybrids
      showed greater resistance than conventional hybrids, although the heterozygous
      genotypes had weaker effects than the corresponding homozygous genotypes.
      Furthermore, field trial data demonstrated that yields of improved 9311 lines
      were higher than or similar to that of the control under natural field
      conditions. These improved versions can be immediately used in hybrid improvement
      and production. CONCLUSION: Compared with controls, pyramided lines and hybrids
      with three genes showed the strongest resistance to BPH, without a yield
      decrease.

PMID- 23175469
TI  - Myeloid leukemia cells with a B7-2(+) subpopulation provoke Th-cell responses and
      become immuno-suppressive through the modulation of B7 ligands.
AB  - Expression of the B7 family molecules in acute myeloid leukemia (AML) has been
      demonstrated by independent clinical studies. Intriguingly, the expression of the
      most potent costimulatory molecules B7-2 (CD86) and B7-H2 (ICOS Ligand) on AML
      cells has been associated with poor prognosis and disease severity. Here, this
      phenomenon was modeled in vitro with the myeloid leukemia cell line HL-60, which
      is capable of differentiating through the FAB M2/M3 and M4/M5 immunophenotypes.
      These derivatives of HL-60 harbored a B7-2(+) subpopulation and recapitulated the
      distribution of B7 ligands previously reported in primary AML cases. B7-2(+) AML
      cells significantly contributed to T-cell responses. This costimulatory activity
      enabled helper (Th)-cell activation, proliferation, and production of Th1
      associated cytokines. Conversely, even a short-term incubation with stimulated T
      cells resulted in upregulation of inhibitory B7-H1 (PD-L1) and B7-DC (PD-L2), and
      downregulation of stimulatory B7-H2 molecules on leukemia cells. Purified from
      iHL-60-T-cell co-cultures, these myeloid leukemia cells severely suppressed Th
      cell responses specifically through the PD-1 pathway. In conclusion, Th-cell
      responses can be directly supported by B7-2(+) leukemia subpopulations. However,
      this interaction can facilitate the acquisition of a suppressive character that
      may contribute to immune evasion in myeloid leukemia.

PMID- 23175470
TI  - Biowaiver monographs for immediate release solid oral dosage forms: efavirenz.
AB  - Literature data pertaining to the decision to allow a waiver of in vivo
      bioequivalence testing for the approval of immediate-release (IR) solid oral
      dosage forms containing efavirenz as the only active pharmaceutical ingredient
      (API) are reviewed. Because of lack of conclusive data about efavirenz's
      permeability and its failure to comply with the "high solubility" criteria
      according to the Biopharmaceutics Classification System (BCS), the API can be
      classified as BCS Class II/IV. In line with the solubility characteristics, the
      innovator product does not meet the dissolution criteria for a "rapidly
      dissolving product." Furthermore, product variations containing commonly used
      excipients or in the manufacturing process have been reported to impact the rate
      and extent of efavirenz absorption. Despite its wide therapeutic index,
      subtherapeutic levels of efavirenz can lead to treatment failure and also
      facilitate the emergence of efavirenz-resistant mutants. For all these reasons, a
      biowaiver for IR solid oral dosage forms containing efavirenz as the sole API is
      not scientifically justified for reformulated or multisource drug products.

PMID- 23175471
TI  - Circulating stem cell-like epithelial cell adhesion molecule-positive tumor cells
      indicate poor prognosis of hepatocellular carcinoma after curative resection.
AB  - Epithelial cell adhesion molecule-positive (EpCAM+) hepatocellular carcinoma
      (HCC) cells may constitute a tumor-initiating subpopulation in tumorigenic cell
      lines and HCC specimens. In the present study, EpCAM+ circulating tumor cells
      (CTCs) were identified prospectively in HCC patients undergoing curative
      resection, and the prognostic significance and their stem cell-like
      characteristics were investigated further. Blood samples from 123 HCC patients
      were tested prior to resection and 1 month thereafter. CTCs were present in
      66.67% of patients, and the cell count measured in 7.5 mL of blood (CTC(7.5) )
      ranged between 1 and 34. Fifty-one patients had CTC(7.5) of >=2 preoperatively,
      and these patients developed tumor recurrence earlier than those with CTC(7.5) of
      <2 CTCs (P < 0.001). A preoperative CTC(7.5) of >=2 was an independent prognostic
      factor for tumor recurrence (P < 0.001). Its prognostic significance also applied
      to patients with alpha-fetoprotein (AFP) levels of <=400 ng/mL or subgroups with
      low recurrence risk (all P < 0.05). A significant decrease of CTC-positive rates
      (66.67% to 28.15%, P < 0.05) and CTC(7.5) values (2.60 +/- 0.43 to 1.00 +/- 0.36,
      P < 0.05) was observed 1 month after resection. Patients with consistent CTC(7.5)
      <2 had lower recurrence rates than those with values consistently >=2 (15.5%
      versus 87.50%, P < 0.001). EpCAM+ CTCs displayed cancer stem cell biomarkers
      (CD133 and ABCG2), epithelial-mesenchymal transition, Wnt pathway activation,
      high tumorigenic potential, and low apoptotic propensity. CONCLUSION: Stem cell
      like phenotypes are observed in EpCAM+ CTCs, and a preoperative CTC(7.5) of >=2
      is a novel predictor for tumor recurrence in HCC patients after surgery,
      especially in patient subgroups with AFP levels of <=400 ng/mL or low tumor
      recurrence risk. EpCAM+ CTCs may serve as a real-time parameter for monitoring
      treatment response and a therapeutic target in HCC recurrence.

PMID- 23175472
TI  - miR-150:targeting MLL leukemia.

PMID- 23175473
TI  - Improvement in sprint performance: doping or nature?

PMID- 23175474
TI  - Occupational stress and its association with early retirement and subjective need
      for occupational rehabilitation in cancer patients.
AB  - OBJECTIVE: Returning to work often plays an important role for cancer survivors.
      Occupational stress may hamper a successful return to work, so cancer survivors
      should be given the opportunity to address occupational stress issues before
      returning to work. We investigated the amount of occupational stress among cancer
      patients and whether it is associated with their well-being, their subjective
      need for occupational rehabilitation and elevations in their risk of early
      retirement. METHODS: At the beginning of rehabilitation, we asked cancer patients
      to respond to occupation-related and health-related questionnaires. We used t
      tests, chi-square tests, and logistic regression analyses to address our research
      questions. RESULTS: A total of 477 patients participated in the study. Of these,
      19% were occupationally stressed, and 26% reported subjective need for
      occupational rehabilitation. Patients who reported work-related stress had a
      diminished quality of life, were more likely to report subjective need for
      occupational rehabilitation (OR = 2.16), and had a higher risk of early
      retirement (OR = 5.44). Furthermore, cancer patients reported deficits in both
      active coping abilities and mental stability at work. CONCLUSIONS: Because
      occupational stress is associated with a higher risk of early retirement, both
      patients and physicians should take work-related problems seriously. Screening
      patients for occupational stress may help physicians identify patients who are at
      risk of experiencing problematic work re-entries. Furthermore, the results of the
      study suggest that cancer patients might have problems maintaining confidence in
      their abilities to solve work-related problems. Therefore, facilitating the
      development of a perception of self-efficacy might be an important treatment
      goal.

PMID- 23175475
TI  - High susceptibility to liver injury in IL-27 p28 conditional knockout mice
      involves intrinsic interferon-gamma dysregulation of CD4+ T cells.
AB  - Interleukin (IL)-27, a newly discovered IL-12 family cytokine, is composed of p28
      and EBI3. In this study, CD11c-p28(f/f) conditional knockout mice were generated
      to delete p28 specifically in dendritic cells (DCs). We demonstrated that in the
      absence of DC-derived p28, these mice were highly susceptible to both low and
      higher concentrations of concanavalin A (ConA) (5 mg/kg or 10 mg/kg), with
      extremely early and steady high levels of interferon-gamma (IFN-gamma) in sera.
      Neutralizing IFN-gamma prevented ConA-induced liver damage in these mice,
      indicating a critical role of IFN-gamma in this pathological process.
      Interestingly, the main source of the increased IFN-gamma in CD11c-p28(f/f) mice
      was CD4+ T cells, but not natural killer T (NKT) cells. Depletion of CD4+ , but
      not NK1.1+ , cells completely abolished liver damage, whereas transferring CD4+ T
      cells from CD11c-p28(f/f) mice, but not from wild-type mice or CD11c-p28(f/f) 
      IFN-gamma(-/-) double knockout mice to CD4(-/-) mice, restored the increased
      liver damage. Further studies defined higher levels of IFN-gamma and T-bet
      messenger RNA in naive CD4+ T cells from CD11c-p28(f/f) mice, and these CD4+ T
      cells were highly responsive to both low and higher concentrations of anti-CD3,
      indicating a programmed functional alternation of CD4+ T cells. CONCLUSION: We
      provide a unique model for studying the pathology of CD4+ T cell-mediated liver
      injury and reveal a novel function of DC-derived p28 on ConA-induced fulminant
      hepatitis through regulation of the intrinsic ability for IFN-gamma production by
      CD4+ T cells.

PMID- 23175476
TI  - Gene expression profiling revealed specific spermatogonial stem cell genes in
      mouse.
AB  - Mammalian spermatogenesis originates from spermatogonial stem cells (SSCs), which
      undergo mitosis, meiosis and spermiogenesis in order to generate mature
      spermatozoa. SSCs are adult stem cells that can both self-renew and
      differentiate. To maintain pluripotency, SSCs are regulated by both extrinsic
      factors secreted from surrounding somatic cells and intrinsic factors including
      specific gene expression programs. Using fluorescent labeled germ line stem
      cells, mouse gonocytes and SSCs were purified up to 97% by improved FACS method.
      Through microarray analyses, global gene expression profiles of gonocytes, SSCs,
      and differentiated cells were compared. A large number of distinctive genes were
      found to be enriched in respective cell populations, indicating different
      functional requirements of each cell type. Functional clustering analyses
      revealed that while gonocytes and SSCs preferentially express genes implicated in
      gene expression regulation and epigenetic modifications, differentiated cells
      including somatic cells are enriched with genes encoding proteins involved in
      various cellular activities. Further in situ hybridization and RT-PCR experiments
      confirmed SSC specific expression of several genes of which functions have not
      been characterized in SSCs. The comparative gene expression profiling provides a
      useful resource for gene discovery in relation to SSC regulation and opens new
      avenues for the study of molecular mechanisms underlying SSC self-renewal and
      differentiation.

PMID- 23175477
TI  - Inhibiting the molecular evolution of cancer through HSP90.

PMID- 23175478
TI  - Trans-splicing and operons in C. elegans.
AB  - About 70% of C. elegans mRNAs are trans-spliced to one of two 22 nucleotide
      spliced leaders. SL1 is used to trim off the 5' ends of pre-mRNAs and replace
      them with the SL1 sequence. This processing event is very closely related to cis
      splicing, or intron removal. The SL1 sequence is donated by a 100 nt small
      nuclear ribonucleoprotein particle (snRNP), the SL1 snRNP. This snRNP is
      structurally and functionally similar to the U snRNAs (U1, U2, U4, U5 and U6)
      that play key roles in intron removal and trans-splicing, except that the SL1
      snRNP is consumed in the process. More than half of C. elegans pre-mRNAs are
      subject to SL1 trans-splicing, whereas ~30% are not trans-spliced. The remaining
      genes are trans-spliced by SL2, which is donated by a similar snRNP, the SL2
      snRNP. SL2 recipients are all downstream genes in closely spaced gene clusters
      similar to bacterial operons. They are transcribed from a promoter at the 5' end
      of the cluster of between 2 and 8 genes. This transcription makes a polycistronic
      pre-mRNA that is co-transcriptionally processed by cleavage and polyadenylation
      at the 3' end of each gene, and this event is closely coupled to the SL2 trans
      splicing event that occurs only ~100 nt further downstream. SL2 trans-splicing
      requires a sequence between the genes, the Ur element, that likely base pairs
      with the 5' splice site on the SL2 snRNP, in a manner analogous to the
      interaction between the 5' splice site in cis-splicing with the U1 snRNP. The key
      difference is that in trans-splicing, the snRNP contains the 5' splice site,
      whereas in cis-splicing the pre-mRNA does. Some operons, termed "hybrid operons",
      contain an additional promoter between two genes that can express the downstream
      gene or genes with a developmental profile that is different from that of the
      entire operon. The operons contain primarily genes required for rapid growth,
      including genes whose products are needed for mitochondrial function and the
      basic machinery of gene expression. Recent evidence suggests that RNA polymerase
      is poised at the promoters of growth genes, and operons allow more efficient
      recovery from growth-arrested states, resulting in reduction in the need for this
      cache of inactive RNA polymerase.

PMID- 23175479
TI  - The many faces of posterior reversible encephalopathy syndrome.
AB  - The classic imaging findings of posterior reversible encephalopathy syndrome
      (PRES) are of bilateral parietal and occipital subcortical vasogenic oedema, and
      are well established in the literature. As experience with PRES grows, varied and
      atypical presentations are being increasingly described. This pictorial review
      illustrates the variable presentations of PRES, including cases with atypical
      imaging findings. We illustrate cases of PRES with varying distributions of
      vasogenic oedema as well as cases with atypical imaging findings, such as
      variations of haemorrhage and restricted diffusion. Atypical imaging findings
      should not dissuade the diagnosis of PRES in the appropriate clinical situation,
      and knowledge of the varied appearance and atypical findings of PRES allows the
      radiologist to make this diagnosis.

PMID- 23175480
TI  - Technical note: 9-month repositioning accuracy for functional response assessment
      in head and neck chemoradiotherapy.
AB  - The use of thermoplastic immobilisation masks in head and neck radiotherapy is
      now common practice. The accuracy of these systems has been widely studied, but
      always within the context and time frame of the radiation delivery-some 6-8
      weeks. There is growing current interest in the use of functional imaging to
      assess the response to treatment, particularly in the head and neck. It is
      therefore of interest to determine the accuracy with which functional images can
      be registered to baseline CT over the extended periods of time used for
      functional response assessment: 3-6 months after radiotherapy. In this study,
      repeated contrast-enhanced diagnostic quality CT and mid-quality localisation CT
      from a positron emission tomography/CT scanner were available for five time
      points over a period of 9 months (before, during and up to 6 months after
      chemoradiotherapy) for a series of eight patients enrolled in a clinical pilot
      study. All images were acquired using thermoplastic immobilisation masks. The
      overall set-up accuracy obtained from this 9-month study of 5.5 +/- 3.2 mm (1
      standard deviation) and 1.9 +/- 1.3 degrees  (1 standard deviation) is in
      agreement with published data acquired over 6-8 weeks. No statistically
      significant change in set-up error was seen with time. This work indicates that
      thermoplastic immobilisation masks can be used to accurately align multimodality
      functional image data for assessment of the response to treatment in head and
      neck patients over extended follow-up periods.

PMID- 23175481
TI  - A right atrial mass--but where is it coming from?

PMID- 23175483
TI  - Radiation-induced cancer: a modern view.
AB  - Diagnostic medical radiation has been the most rapidly increasing component of
      population background radiation exposure in Western countries over the past
      decade. This trend is set to increase as CT scanning is readily available with
      burgeoning use in everyday clinical practice. Consequently, the issue of cancer
      induction from the doses received during diagnostic medical exposures is highly
      relevant. In this review we explain current understanding of potential cancer
      induction at low doses of sparsely ionising radiation. For cancers that may be
      induced at low doses, a mechanistic description of radiation-induced cancer is
      discussed, which, in combination with extrapolation of data based on population
      cohort studies, provides the basis of the currently accepted linear no-threshold
      model. We explore the assumptions made in deriving risk estimates, the
      controversies surrounding the linear no-threshold model and the potential future
      challenges facing clinicians and policy-makers with regards to diagnostic medical
      radiation and cancer risk, most notably the uncertainties regarding deriving risk
      estimates from epidemiological data at low doses.

PMID- 23175484
TI  - Application of breast tomosynthesis in screening: incremental effect on
      mammography acquisition and reading time.
AB  - OBJECTIVE: The aim of this study was to supplement the paucity of information
      available on logistical aspects of the application of three-dimensional (3D)
      mammography in breast screening. METHODS: We prospectively examined the effect on
      radiographers' and radiologists' workload of implementing 3D mammography in
      screening by comparing image acquisition time and screen-reading time for two
      dimensional (2D) mammography with that of combined 2D+3D mammography.
      Radiologists' accuracy was also calculated. RESULTS: Average acquisition time
      (measured from start of first-view breast positioning to compression release at
      completion of last view) for seven radiographers, based on 20 screening
      examinations, was longer for 2D+3D (4 min 3 s; range 3 min 53 s-4 min 18 s) than
      2D mammography (3 min 13 s; range 3 min 0 s-3 min 26 s; p<0.01). Average
      radiologists' reading time per screening examination (three radiologists reading
      case-mix of 100 screens: 10 cancers, 90 controls) was longer for 2D+3D (77 s;
      range 60-90 s) than for 2D mammography (33 s; range 25-46 s; p<0.01). 2D+3D
      screen-reading was associated with detection of more cancers and with
      substantially fewer recalls than 2D mammography alone. CONCLUSION: Relative to
      standard 2D mammography, combined 2D+3D mammography prolongs image acquisition
      time and screen-reading time (at initial implementation), and appears to be
      associated with improved screening accuracy. ADVANCES IN KNOWLEDGE: These
      findings provide relevant information to guide larger trials of integrated 3D
      mammography (2D+3D) and its potential implementation into screening practice.

PMID- 23175485
TI  - Assessing response of myeloma bone disease with diffusion-weighted MRI.
AB  - OBJECTIVES: To measure apparent diffusion coefficient (ADC) values in patients
      with active myeloma and remission and to determine whether changes differ in
      those responding/progressing on treatment. The relationship between changes in
      marrow fat and ADC was also explored. METHODS: 20 patients were recruited. T(1
      )weighted, T(2) weighted, short tau inversion-recovery, diffusion-weighted and
      two-point Dixon MRI of the lumbar spine and pelvis were performed at baseline, 4
      6 weeks and 20 weeks. RESULTS: ADC values of active disease (mean 761.2 +/-
      255*10(-6) mm(2) s(-1)) were significantly higher (p=0.047) than marrow in
      remission (mean 601.8 +/- 459*10(-6) mm(2) s(-1)). Changes in ADC in responders
      showed a significant increase at 4-6 weeks (p=0.005) but no significant change
      between baseline and 20 weeks (p=0.733). ADCs in progressing and stable patients
      did not change significantly between either time point. Pearson's correlation
      coefficient between change in fat fraction and change in the number of pixels
      with an ADC of <=655*10(-6) mm(2) s(-1) was 0.924, indicating a significant
      correlation (p<0.001). CONCLUSION: ADC values in active myeloma are significantly
      higher than marrow in remission, indicating the potential for diffusion-weighted
      MRI to quantify the transition from active disease to remission and vice versa.
      This study confirms significant changes in ADC in patients responding to
      treatment and indirect evidence from two-point Dixon MRI suggests that these
      changes are influenced by changes in marrow fat. ADVANCES IN KNOWLEDGE: ADC of
      active myeloma is significantly higher than marrow in remission; the direction of
      ADC changes on treatment is dependent on the timing of measurements and is
      influenced by changes in marrow fat.

PMID- 23175486
TI  - Semi-automated and automated glioma grading using dynamic susceptibility-weighted
      contrast-enhanced perfusion MRI relative cerebral blood volume measurements.
AB  - OBJECTIVE: Despite the established role of MRI in the diagnosis of brain tumours,
      histopathological assessment remains the clinically used technique, especially
      for the glioma group. Relative cerebral blood volume (rCBV) is a dynamic
      susceptibility-weighted contrast-enhanced perfusion MRI parameter that has been
      shown to correlate to tumour grade, but assessment requires a specialist and is
      time consuming. We developed analysis software to determine glioma gradings from
      perfusion rCBV scans in a manner that is quick, easy and does not require a
      specialist operator. METHODS: MRI perfusion data from 47 patients with different
      histopathological grades of glioma were analysed with custom-designed software.
      Semi-automated analysis was performed with a specialist and non-specialist
      operator separately determining the maximum rCBV value corresponding to the
      tumour. Automated histogram analysis was performed by calculating the mean,
      standard deviation, median, mode, skewness and kurtosis of rCBV values. All
      values were compared with the histopathologically assessed tumour grade. RESULTS:
      A strong correlation between specialist and non-specialist observer measurements
      was found. Significantly different values were obtained between tumour grades
      using both semi-automated and automated techniques, consistent with previous
      results. The raw (unnormalised) data single-pixel maximum rCBV semi-automated
      analysis value had the strongest correlation with glioma grade. Standard
      deviation of the raw data had the strongest correlation of the automated
      analysis. CONCLUSION: Semi-automated calculation of raw maximum rCBV value was
      the best indicator of tumour grade and does not require a specialist operator.
      ADVANCES IN KNOWLEDGE: Both semi-automated and automated MRI perfusion techniques
      provide viable non-invasive alternatives to biopsy for glioma tumour grading.

PMID- 23175487
TI  - Kinetics of intravenous radiographic contrast medium injections as used on CT:
      simulation with time delay differential equations in a basic human cardiovascular
      multicompartment model.
AB  - OBJECTIVES: To develop a multicompartment model of only essential human body
      components that predicts the contrast medium concentration vs time curve in a
      chosen compartment after an intravenous injection. Also to show that the model
      can be used to time adequately contrast-enhanced CT series. METHODS: A system of
      linked time delay instead of ordinary differential equations described the model
      and was solved with a Matlab program (Matlab v. 6.5; The Mathworks, Inc., Natick,
      MA). All the injection and physiological parameters were modified to cope with
      normal or pathological situations. In vivo time-concentration curves from the
      literature were recalculated to validate the model. RESULTS: The recalculated
      contrast medium time-concentration curves and parameters are given. The results
      of the statistical analysis of the study findings are expressed as the median
      prediction error and the median absolute prediction error values for both the
      time delay and ordinary differential equation systems; these are situated well
      below the generally accepted maximum 20% limit. CONCLUSION: The presented program
      correctly predicts the time-concentration curve of an intravenous contrast medium
      injection and, consequently, allows an individually tailored approach of CT
      examinations with optimised use of the injected contrast medium volume, as long
      as time delay instead of ordinary differential equations are used. ADVANCES IN
      KNOWLEDGE: The presented program offers good preliminary knowledge of the time
      contrast medium concentration curve after any intravenous injection, allowing
      adequate timing of a CT examination, required by the short scan time of present
      day scanners. The injected volume of contrast medium can be tailored to the
      individual patient with no more contrast medium than is strictly needed.

PMID- 23175488
TI  - Comparison of the clinical characteristics and imaging findings of acute
      cholangitis with and without biliary dilatation.
AB  - OBJECTIVE: To evaluate the causes of acute cholangitis without biliary dilatation
      and to compare the clinical characteristics and the imaging findings between
      patients with acute cholangitis with and without biliary dilatation. METHODS: 93
      patients diagnosed with acute cholangitis underwent contrast-enhanced CT. Among
      them, 17 patients were classified as not having biliary dilatation (Group 1) and
      76 patients were classified as having biliary dilatation (Group 2). The causes of
      acute cholangitis were evaluated in both groups. Clinical characteristics and
      imaging findings were compared between the two groups. RESULTS: The causes of
      acute cholangitis without biliary dilatation included common bile duct (CBD)
      stones (n=11), CBD sludge (n=3), a passed stone (n=1) and unknown causes (n=2).
      The total bilirubin levels of Group 1 were significantly lower than those of
      Group 2 (p=0.001). By contrast, Group 1 had higher median alanine
      aminotransferase (ALT) levels than Group 2 (p=0.04). The length of hospital stay
      was significantly longer in Group 2 than in Group 1 patients (p<0.001). In the
      imaging findings, the extent of transient hepatic attenuation differences (THADs)
      (p=0.003) were significantly smaller in Group 1 than in Group 2. CONCLUSION: CBD
      stones and sludge were the most common causes of acute cholangitis in patients
      without biliary dilatation. These patients showed lower levels of bilirubin and
      higher levels of ALT than those with acute cholangitis with biliary dilatation,
      and had a shorter duration of hospital stay. The extent of THADs was the only
      discriminative CT finding between the two groups. ADVANCES IN KNOWLEDGE: Acute
      cholangitis can present without biliary dilatation on imaging, and the most
      common causes are CBD stones and sludge. The patients with acute cholangitis
      without biliary dilatation have different clinical characteristics and imaging
      findings compared with those with acute cholangitis presenting with biliary
      dilatation.

PMID- 23175489
TI  - Mechanistic modelling of radiotherapy-induced lung toxicity.
AB  - OBJECTIVE: This work explores the biological basis of a mechanistic model of
      radiation-induced lung damage; uniquely, the model makes a connection between the
      cellular radiobiology involved in lung irradiation and the full three-dimensional
      distribution of radiation dose. METHODS: Local tissue damage and loss of global
      organ function, in terms of radiation pneumonitis (RP), were modelled as
      different levels of radiation injury. Parameters relating to the former could be
      derived from the local dose-response function, and the latter from the volume
      effect of the organ. The literature was consulted to derive information on a
      threshold dose and volume-effect mechanisms. RESULTS: Simulations of local tissue
      damage supported the alveolus as a functional subunit (FSU) which can be
      regenerated from a single surviving stem cell. A moderate interpatient variation
      in stem cell radiosensitivity (15%) resulted in a great variation in tissue
      response between 8 and 20 Gy. The threshold of FSU inactivation within a critical
      functioning volume leading to RP was found to be approximately 47% and the degree
      of health status variation (influencing the volume effect) in a population was
      estimated at 25%. CONCLUSION: This work has shown that it is possible to make
      sense of the way the lung responds to radiation by modelling RP mechanistically,
      from cell death to tissue damage to loss of organ function. ADVANCES IN
      KNOWLEDGE: Simulations were able to provide parameter values, currently not
      available in the literature, related to the response of the lung to irradiation.

PMID- 23175490
TI  - Dose escalation in brachytherapy for cervical cancer: impact on (or increased
      need for) MRI-guided plan optimisation.
AB  - OBJECTIVE: The aim of this study was to assess the impact of dose escalation on
      the proportion of patients requiring MR image-guided optimisation rather than
      standard Manchester-based CT-guided planning, and the level of escalation
      achievable. METHODS: 30 patients with cervical cancer treated with external beam
      radiotherapy and image-guided brachytherapy (IGBT) had MR images acquired at the
      first fraction of IGBT. Gross tumour volume and high-risk clinical target volume
      (HR CTV) were contoured and treatment plans retrospectively produced for a range
      of total 2-Gy equivalent (EQD2) prescription doses from 66 Gy(alpha/beta=10) to
      90 Gy(alpha/beta=10) (HR CTV D90). Standard Manchester system-style plans were
      produced, prescribed to point A and then optimised where necessary with the aim
      of delivering at least the prescription dose to the HR CTV D90 while respecting
      organ-at-risk (OAR) tolerances. RESULTS: Increasing the total EQD2 from 66
      Gy(alpha/beta=10) to 90 Gy(alpha/beta=10) increased the number of plans requiring
      optimisation from 13.3% to 90%. After optimisation, the number of plans achieving
      the prescription dose ranged from 93.3% (66 Gy(alpha/beta=10)) to 63.3% (90
      Gy(alpha/beta=10)) with the mean +/- standard deviation for HR CTV D90 EQD2 from
      78.4 +/- 12.4 Gy(alpha/beta=10) (66 Gy(alpha/beta=10)) to 94.1 +/- 19.9
      Gy(alpha/beta=10) (90 Gy(alpha/beta=10)). CONCLUSION: As doses are escalated, the
      need for non-standard optimised planning increases, while benefits in terms of
      increased target doses actually achieved diminish. The maximum achievable target
      dose is ultimately limited by proximity of OARs. ADVANCES IN KNOWLEDGE: This work
      represents a guide for other centres in determining the highest practicable
      prescription doses while considering patient throughput and maintaining
      acceptable OAR doses.

PMID- 23175491
TI  - The influence of MRI scan position on image registration accuracy, target
      delineation and calculated dose in prostatic radiotherapy.
AB  - OBJECTIVE: To investigate the necessity of performing MRI in the radiotherapy
      position when using MRI for prostatic radiotherapy. METHODS: 20 prostate patients
      received a CT, diagnostic MRI and an MRI scan in the radiotherapy position. The
      quality of registration between CT and MRI was compared between the two MRI set
      ups. The prostate and seminal vesicles were contoured using all scans and
      intensity modulated radiotherapy (IMRT) plans were generated. Changes in the
      target volume and IMRT plans were investigated. Two-tailed paired Student's t
      tests determined the statistical significance. RESULTS: There was a decrease in
      the mean distance from the centre of the bony anatomy between CT and MRI (from
      3.9 to 1.9 mm, p-value<0.0001) when the MRI scan was acquired in the radiotherapy
      position. Assuming that registering CT with an MRI scan in the radiotherapy
      position is the gold standard for delineating the prostate and seminal vesicles,
      using a planning target volume delineated on the CT with a diagnostic MRI scan
      viewed separately, resulted in a mean conformation number of 0.80 instead of the
      expected 0.98 (p<0.0001). CONCLUSION: By registering CT with an MRI scan in the
      radiotherapy position, there is a statistically significant improvement in the
      registration and IMRT quality. ADVANCES IN KNOWLEDGE: To achieve an acceptable
      registration and IMRT quality in prostatic radiotherapy, neither CT with a
      separate diagnostic MRI nor CT registered to a diagnostic MRI will suffice.
      Instead, a CT registered with an MRI in the radiotherapy position should be used.

PMID- 23175492
TI  - Modelling the throughput capacity of a single-accelerator multitreatment room
      proton therapy centre.
AB  - OBJECTIVE: We describe a model for evaluating the throughput capacity of a single
      accelerator multitreatment room proton therapy centre with the aims of (1)
      providing quantitative estimates of the throughput and waiting times and (2)
      providing insight into the sensitivity of the system to various physical
      parameters. METHODS: A Monte Carlo approach was used to compute various
      statistics about the modelled centre, including the throughput capacity, fraction
      times for different groups of patients and beam waiting times. A method of
      quantifying the saturation level is also demonstrated. RESULTS: Benchmarking
      against the MD Anderson Cancer Center showed good agreement between the modelled
      (140 +/- 4 fractions per day) and reported (133 +/- 35 fractions per day)
      throughputs. A sensitivity analysis of that system studied the impact of beam
      switch time, the number of treatment rooms, patient set-up times and the
      potential benefit of having a second accelerator. Finally, scenarios relevant to
      a potential UK facility were studied, finding that a centre with the same four
      room, single-accelerator configuration as the MD Anderson Cancer Center but
      handling a more complex UK-type caseload would have a throughput reduced by
      approximately 19%, but still be capable of treating in excess of 100 fractions
      per 16-h treatment day. CONCLUSIONS: The model provides a useful tool to aid in
      understanding the operating dynamics of a proton therapy facility, and for
      investigating potential scenarios for prospective centres. ADVANCES IN KNOWLEDGE:
      The model helps to identify which technical specifications should be targeted for
      future improvements.

PMID- 23175493
TI  - Clinical commissioning of online seed matching protocol for prostate
      radiotherapy.
AB  - OBJECTIVES: Our aim was to clinically commission an online seed matching image
      guided radiotherapy (IGRT) protocol using modern hardware/software for patients
      undergoing prostate radiotherapy. An essential constraint was to achieve this
      within a busy centre without reducing patient throughput, which had been reported
      with other techniques. METHODS: 45 patients had 3 fiducial markers inserted into
      the prostate and were imaged daily using kilovoltage orthogonal images with
      online correction applied before treatment. A total of 1612 image pairs were
      acquired and analysed to identify interfractional motion, seed migration and
      interobserver variability, and assess ease of use. RESULTS: This method of IGRT
      was implemented successfully in our centre with no impact on treatment times and
      patient throughput. Systematic (Sigma) interfractional set-up errors were 2.2,
      2.7 and 3.9 mm in right-left (RL), superoinferior (SI) and anteroposterior (AP)
      directions, respectively. Random (sigma) interfractional set-up errors were 3.2
      (RL), 3.7 (SI) and 5.7 mm (AP). There were significant differences between
      patients. Seed migration and interobserver variability were not significant
      issues. CONCLUSIONS: The described technique is facilitated by the advanced
      imaging system, allowing a fast and effective method of correcting set-up errors
      before treatment. Extended implementation of this technique has improved
      treatment delivery to the majority of our prostate radiotherapy patients. The
      measurement of interfractional motion in this study is potentially valuable for
      margin reduction in intensity-modulated radiotherapy/volumetric arc therapy.
      ADVANCES IN KNOWLEDGE: This technique can be used within treatment time
      constraints, benefiting large numbers of patients by helping to avoid
      geographical miss and potentially reducing toxicity to organs at risk.

PMID- 23175495
TI  - Pre-operative CT angiography and three-dimensional image post processing for deep
      inferior epigastric perforator flap breast reconstructive surgery.
AB  - Autologous breast reconstructive surgery with deep inferior epigastric artery
      (DIEA) perforator flaps has become the mainstay for breast reconstructive
      surgery. CT angiography and three-dimensional image post processing can depict
      the number, size, course and location of the DIEA perforating arteries for the
      pre-operative selection of the best artery to use for the tissue flap. Knowledge
      of the location and selection of the optimal perforating artery shortens
      operative times and decreases patient morbidity.

PMID- 23175494
TI  - Takayasu arteritis: imaging spectrum at multidetector CT angiography.
AB  - Takayasu arteritis is a chronic, idiopathic, inflammatory disease that primarily
      affects large vessels, such as the aorta and its major branches and the pulmonary
      and coronary arteries. The non-specific inflammation of involved vessels usually
      leads to concentric wall thickening, fibrosis and thrombus formation. Diseased
      arteries become stenotic or occluded, undergo vascular remodelling or develop
      aneurysms. According to the involvement of arteries, six types of Takayasu
      arteritis are documented. The purpose of this pictorial review is to illustrate
      the various multidetector CT angiography appearances of Takayasu arteritis and to
      discuss the differential diagnosis.

PMID- 23175496
TI  - Cancer risks from diagnostic radiology: the impact of new epidemiological data.

PMID- 23175497
TI  - Sonographically guided triamcinolone injection for the treatment of chronic post
      operative mammillary fistula.
AB  - We describe ultrasound-guided intralesional triamcinolone (ILT) injection for the
      management of chronic post-operative mammillary fistula (MF). Seven patients with
      chronic post-operative intraglandular MF were enrolled in this study. The initial
      response to treatment was assessed as complete in three cases; of the remaining
      four, three were resolved successfully with an additional ILT injection and the
      other had no resolution with an additional ILT injection. In five cases there was
      no recurrence after more than 1 year of follow-up. One patient had recurrence at
      7 months, which was treated with a further ILT injection; this patient is without
      recurrence after a further 9 months' follow-up. This simple, safe procedure is
      suggested as an option for the treatment of chronic post-operative intraglandular
      MF and may be an alternative to surgery.

PMID- 23175498
TI  - The irrational attraction of elective single-embryo transfer (eSET).
AB  - In this issue of the journal, Niinimaki et al., colleagues from a pioneering
      Finnish center in the development of elective single-embryo transfer (eSET),
      propose the expansion of eSET to suitable women at ages of 40-44 years. This
      paper offers not only a critique of their proposal but also of eSET in general.

PMID- 23175499
TI  - Elective single-embryo transfer in women aged 40-44 years.
AB  - STUDY QUESTION: Is an elective single-embryo transfer (eSET) policy feasible for
      women aged 40 or older? SUMMARY ANSWER: For older women (aged 40-44 years) with a
      good prognosis, an eSET policy can be applied with acceptable cumulative clinical
      pregnancy rates and live birth rates. WHAT IS KNOWN ALREADY: Various studies have
      shown the effectiveness of eSET in women aged <35 years with high cumulative
      pregnancy rates and low rates of multiple births. STUDY DESIGN, SIZE, DURATION:
      This retrospective cohort study included 628 women treated between 2000 and 2009.
      PARTICIPANTS, SETTING, METHODS: Women aged 40-44 years underwent a fresh cycle of
      IVF or ICSI treatment with eSET (n = 264) or double-embryo transfer (DET) (n =
      364). In the subsequent frozen-thawed embryo transfer cycles, SET/DET was
      performed in both groups according to the number of embryos available and the
      opinion of the couple. The study was performed at the Family Federation of
      Finland Helsinki Fertility Clinic. MAIN RESULTS AND THE ROLE OF CHANCE: In the
      fresh cycles, the clinical pregnancy rates were 23.5 and 19.5% in the eSET and
      DET groups, respectively, and live birth rates were 13.6 and 11.0%, respectively.
      In the fresh cycles with eSET, there were no twin pregnancies, but in the DET
      group, there were three sets of twins (7.5%). The cumulative clinical pregnancy
      rates per oocyte retrieval were 37.1 and 24.2% in the eSET and DET groups,
      respectively (P < 0.001), and the cumulative live birth rates were 22.7 and
      13.2%, respectively (P = 0.002). Cumulative twin rates were 6.7% (n = 4) in the
      eSET group and 8.3% (n = 4) in the DET group (P = 0.726). All of the twin
      pregnancies in the eSET group resulted from frozen and thawed DET embryo transfer
      cycles. LIMITATIONS: The characteristics of the two patients groups are not
      comparable because the suitability of eSET was individually assessed by a
      clinician based on both clinical prognostic factors and the outcome of IVF or
      ICSI, i.e. the number and quality of embryos. WIDER IMPLICATIONS OF THE FINDINGS:
      This study may be generalized to IVF units having experience in eSET and
      cryopreservation.

PMID- 23175501
TI  - Five years (2004-2009) of a restrictive law-regulating ART in Italy significantly
      reduced delivery rate: analysis of 10,706 cycles.
AB  - STUDY QUESTION: Was the delivery rate of ART cycles negatively affected by the
      enactment of the Law 40/2004 by the Italian Parliament which imposed a long list
      of restrictions for ART procedures? SUMMARY ANSWER: This large and extensive
      comparative analysis of ART outcomes prior to and after the introduction of the
      Law 40 revealed a significant reduction in pregnancy and delivery rates per
      cycle, independent of age or other clinical variables, once the law went into
      effect. WHAT IS KNOWN ALREADY: Several studies have been published on the effect
      of Law 40/2004 on ART outcomes, some authors demonstrating a negative impact of
      the Law in relation to specific etiologies of infertility, other authors showing
      opposite conclusions. STUDY DESIGN, SIZE, DURATION: Retrospective clinical study
      of 3808 patients treated prior to the enactment of the Law, September 1996-March
      2004 (Group I) and 6898 treated during the Law, March 2004-May 2009 (Group II).
      PARTICIPANTS/MATERIALS, SETTING, METHODS: A total of 10 706 ART cycles were
      analysed, 3808 performed before and 6898 after the application of the Law. An
      intention-to-treat statistical analysis was performed to detect pregnancy and
      delivery rates (pregnancies >= 24 weeks) per started cycle. A P value of <0.05
      was considered statistically significant. We analysed different outcomes:
      differences in fertilization, pregnancy and delivery rate, multiple pregnancies
      and miscarriage rates between the two time periods. MAIN RESULTS AND THE ROLE OF
      CHANCE: The delivery rate for started cycle was 20% before and 16.0% after the
      introduction of the Law representing a 25% reduction (P < 0.001). The
      multivariate analysis, corrected by female age of >38 years, duration of
      infertility, basal FSH level and number of retrieved oocytes, showed a 16% lower
      delivery rate (odds ratio: 0.84; confidence interval: 0.75-0.94). This
      statistical approach removed the risk that the observed effects were due to
      chance and confirmed unequivocally that the Law was an independent factor
      responsible for the reduced likelihood of a successful outcome. LIMITATIONS,
      REASONS FOR CAUTION: This is a retrospective study. A prospective randomized
      study, with patients treated in the same time period and randomized to
      restrictions or not, would have minimized potential limitations due to
      differences in years of treatments. WIDER IMPLICATIONS OF THE FINDINGS: Our
      findings based on the analysis of such a large number of cycles proved clearly
      and unequivocally that imposing restrictions on the practice of ART penalized
      patients. These data represent a relevant clinical contribution for countries
      still debating the enactment of restrictive limitations of ART.

PMID- 23175500
TI  - Validity of self-reported data on pregnancies for childhood cancer survivors: a
      comparison with data from a nationwide population-based registry.
AB  - STUDY QUESTION: To what degree do records registered in the Netherlands Perinatal
      Registry (PRN) agree with self-report in a study questionnaire on pregnancy
      outcomes in childhood cancer survivors (CCSs)? SUMMARY ANSWER: This study
      suggests that self-reported pregnancy outcomes of CCSs agree well with registry
      data and that outcomes reported by CCSs agree better with registry data than do
      those of controls. WHAT IS KNOWN ALREADY: Many studies have shown that childhood
      cancer treatment may affect fertility outcomes in female CCSs; however, these
      conclusions were often based on questionnaire data, and it remains unclear
      whether self-report agrees well with more objective sources of information. STUDY
      DESIGN, SIZE, DURATION: In an nationwide cohort study on fertility (inclusion
      period January 2008 and April 2011, trial number: NTR2922), 1420 CCSs and 354
      sibling controls were invited to complete a questionnaire regarding socio
      demographic characteristics and reproductive history. In total, 879 CCSs (62%)
      and 287 controls (81%) returned the questionnaire. PARTICIPANTS/MATERIALS,
      SETTING, METHODS: The current validation study compared the agreement between
      pregnancy outcomes as registered in the PRN and self-reported outcomes in the
      study questionnaire. A total of 589 pregnancies were reported in CCSs, and 300
      pregnancies in sibling controls, of which 524 could be linked to the PRN. MAIN
      RESULTS AND THE ROLE OF CHANCE: A high intra-class correlation coefficient (ICC)
      was found for birthweight (BW) (0.94 and 0.87 for CCSs and controls,
      respectively). The self-reported BWs tended to be higher than reported in the
      PRN. For gestational age (GA), the ICC was high for CCSs (0.88), but moderate for
      controls (0.49). CCSs overestimated GA more often than controls. The Kappa values
      for method of conception and for method of delivery were moderate to good.
      Multilevel analyses on the mean difference with regard to BW and GA showed no
      differences associated with time since pregnancy or educational level.
      LIMITATIONS, REASONS FOR CAUTION: Not all pregnancies reported could be linked to
      the registry data. In addition, the completeness of the PRN could not be assessed
      precisely, because there is no information on the number of missing records.
      Finally, for some outcomes there were high proportions of missing values in the
      PRN registry. WIDER IMPLICATIONS OF THE FINDINGS: Our study suggests that
      questionnaires are a reliable method of data collection, and that for most
      variables, self-report agrees well with registry data. STUDY FUNDING/COMPETING
      INTEREST: This work was supported by the Dutch Cancer Society (grant no. VU 2006
      3622) and by Foundation Children Cancer Free. None of the authors report a
      conflict of interest. TRIAL REGISTRATION NUMBER: NTR2922
      http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=2922.

PMID- 23175502
TI  - Genetic induction of the Warburg effect inhibits tumor growth.

PMID- 23175503
TI  - The nucleoid-associated protein HUbeta affects global gene expression in
      Porphyromonas gingivalis.
AB  - HU is a non-sequence-specific DNA-binding protein and one of the most abundant
      nucleoid-associated proteins in the bacterial cell. Like Escherichia coli, the
      genome of Porphyromonas gingivalis is predicted to encode both the HUalpha
      (PG1258) and the HUbeta (PG0121) subunit. We have previously reported that PG0121
      encodes a non-specific DNA-binding protein and that PG0121 is co-transcribed with
      the K-antigen capsule synthesis operon. We also reported that deletion of PG0121
      resulted in downregulation of capsule operon expression and produced a P.
      gingivalis strain that is phenotypically deficient in surface polysaccharide
      production. Here, we show through complementation experiments in an E. coli
      MG1655 hupAB double mutant strain that PG0121 encodes a functional HU homologue.
      Microarray and quantitative RT-PCR analysis were used to further investigate
      global transcriptional regulation by HUbeta using comparative expression
      profiling of the PG0121 (HUbeta) mutant strain to the parent strain, W83. Our
      analysis determined that expression of genes encoding proteins involved in a
      variety of biological functions, including iron acquisition, cell division and
      translation, as well as a number of predicted nucleoid associated proteins were
      altered in the PG0121 mutant. Phenotypic and quantitative real-time-PCR (qRT-PCR)
      analyses determined that under iron-limiting growth conditions, cell division and
      viability were defective in the PG0121 mutant. Collectively, our studies show
      that PG0121 does indeed encode a functional HU homologue, and HUbeta has global
      regulatory functions in P. gingivalis; it affects not only production of capsular
      polysaccharides but also expression of genes involved in basic functions, such as
      cell wall synthesis, cell division and iron uptake.

PMID- 23175505
TI  - A CsrA/RsmA translational regulator gene encoded in the replication region of a
      Sinorhizobium meliloti cryptic plasmid complements Pseudomonas fluorescens rsmA/E
      mutants.
AB  - Members of the CsrA/RsmA family are global regulatory proteins that bind to
      mRNAs, usually at the ribosome-binding site, to control mRNA translation and
      stability. Their activity is counteracted by small non-coding RNAs (sRNAs), which
      offer several binding sites to compete with mRNA binding. The csrA/rsmA genes are
      widespread in prokaryotic chromosomes, although certain phylogenetic groups such
      as Alphaproteobacteria lack this type of global regulator. Interestingly, a
      csrA/rsmA-like sequence was identified in the replication region of plasmid
      pMBA19a from the alphaproteobacterium Sinorhizobium meliloti. This rsmA-like
      allele (rsmA(Sm)) is 58 % identical to Xanthomonas axonopodis pv. citri
      chromosomal rsmA and bears an unusual C-terminal extension that may fold into an
      extra alpha-helix. Homology-based modelling of RsmA(Sm) suggests that all key
      mRNA-binding residues are conserved and correctly positioned in the RNA-binding
      pocket. In fact, a 1.6 kb fragment from pMBA19a encompassing the rsmA(Sm) locus
      restored rsmA/E-dependent phenotypes of rsmA/E gacS Pseudomonas fluorescens
      mutants. The functionality of RsmA(Sm) was confirmed by the gain of control over
      target aprA'-'lacZ and hcnA'-'lacZ translational fusions in the same mutant
      background. The RsmA(Sm) activity correlated with Western blot detection of the
      polypeptide. Phenotype and translational fusion data from rsmA/E P. fluorescens
      mutants expressing RsmX/Y/Z RNAs indicated that RsmA(Sm) is able to bind these
      antagonistic sRNAs. In agreement with the latter observation, it was also found
      that the sRNA RsmY was stabilized by RsmA(Sm). Deletion of the C-terminal extra
      alpha-helix of RsmA(Sm) affected its cellular concentration, but increased its
      relative RNA-binding activity. This is believed to be the first report of the
      presence and characterization of a functional csrA/rsmA homologue in a mobile
      genetic element.

PMID- 23175504
TI  - OmpR regulation of the uropathogenic Escherichia coli fimB gene in an acidic/high
      osmolality environment.
AB  - Uropathogenic Escherichia coli (UPEC) causes more than 90 % of all human urinary
      tract infections through type 1 piliated UPEC cells binding to bladder epithelial
      cells. The FimB and FimE site-specific recombinases orient the fimS element
      containing the fimA structural gene promoter. Regulation of fimB and fimE depends
      on environmental pH and osmolality. The EnvZ/OmpR two-component system affects
      osmoregulation in E. coli. To ascertain if OmpR directly regulated the fimB gene
      promoters, gel mobility shift and DNase I footprinting experiments were performed
      using OmpR or phosphorylated OmpR (OmpR-P) mixed with the fimB promoter regions
      of UPEC strain NU149. Both OmpR-P and OmpR bound weakly to one fimB promoter.
      Because there was weak binding to one fimB promoter, strain NU149 was grown in
      different pH and osmolality environments, and total RNAs were extracted from each
      population and converted to cDNAs. Quantitative reverse-transcriptase PCR showed
      no differences in ompR transcription among the different growth conditions.
      Conversely, Western blots showed a significant increase in OmpR protein in UPEC
      cells grown in a combined low pH/high osmolality environment versus a neutral
      pH/high osmolality environment. In a high osmolality environment, the ompR mutant
      expressed more fimB transcripts and Phase-ON positioning of the fimS element as
      well as higher type 1 pili levels than wild-type cells. Together these results
      suggest that OmpR may be post-transcriptionally regulated in UPEC cells growing
      in a low pH/high osmolality environment, which regulates fimB in UPEC.

PMID- 23175506
TI  - DNA unmasked in the red rain cells of Kerala.
AB  - Extraordinary claims have been made for the biological properties of the red rain
      cells of Kerala, including a suggestion that they lack DNA. We have investigated
      the fluorescence properties of red rain cells, and the solubility of the red
      pigment in a variety of solvents. Extraction of the pigment with DMSO allowed
      successful demonstration of DNA using DAPI staining. Cellular impermeability to
      staining reagents due to the red pigment is the likely explanation for the
      failure of previous efforts to demonstrate DNA in red rain cells.

PMID- 23175508
TI  - A qualitative study: professionals' experiences of advance care planning in
      dementia and palliative care, 'a good idea in theory but ...'.
AB  - BACKGROUND: Advance care planning comprises discussions about an individual's
      wishes for future care while they have capacity. AIM: To explore professionals'
      experiences on the implementation of advance care planning in two areas of
      clinical care, dementia and palliative care. DESIGN: Qualitative study, focus
      groups and individual interviews. SETTING: North East of England. SAMPLE: Ninety
      five participants from one Primary Care Trust, two acute National Health Service
      Hospital Trusts, one Ambulance Trust, one Local Authority and voluntary
      organisations and the legal sector. RESULTS: Fourteen focus groups and 18
      interviews were held with 95 participants. While professionals agreed that
      advance care planning was a good idea in theory, implementation in practice
      presented them with significant challenges. The majority expressed uncertainty
      over the general value of advance care planning, whether current service
      provision could meet patient wishes, their individual roles and responsibilities
      and which aspects of advance care planning were legally binding; the array of
      different advance care planning forms and documentation available added to the
      confusion. In dementia care, the timing of when to initiate advance care planning
      discussions was an added challenge. CONCLUSIONS: This study has identified the
      professional, organisational and legal factors that influence advance care
      planning implementation; professional training should target these specific
      areas. There is an urgent need for standardisation of advance care planning
      documentation. Greater clarity is also required on the roles and responsibilities
      of different professional groups. More complex aspects of advance care planning
      may be better carried out by those with specialist skills and experience than by
      generalists caring for a wide range of patient groups with different disease
      trajectories.

PMID- 23175507
TI  - Pre-existing immunity against vaccine vectors--friend or foe?
AB  - Over the last century, the successful attenuation of multiple bacterial and viral
      pathogens has led to an effective, robust and safe form of vaccination. Recently,
      these vaccines have been evaluated as delivery vectors for heterologous antigens,
      as a means of simultaneous vaccination against two pathogens. The general
      consensus from published studies is that these vaccine vectors have the potential
      to be both safe and efficacious. However, some of the commonly employed vectors,
      for example Salmonella and adenovirus, often have pre-existing immune responses
      in the host and this has the potential to modify the subsequent immune response
      to a vectored antigen. This review examines the literature on this topic, and
      concludes that for bacterial vectors there can in fact, in some cases, be an
      enhancement in immunogenicity, typically humoral, while for viral vectors pre
      existing immunity is a hindrance for subsequent induction of cell-mediated
      responses.

PMID- 23175509
TI  - Hospice experiences and approaches to support and assess family caregivers in
      managing medications for home hospice patients: a providers survey.
AB  - BACKGROUND: Hospice providers need to ensure that informal, unpaid caregivers can
      safely manage medications to alleviate pain and distressing symptoms in patients
      near the end of life. AIM: This study characterizes hospice providers' self
      reported experiences and approaches to helping caregivers' medication management
      for home hospice patients. DESIGN: Survey with mixed-method analysis.
      SETTING/PARTICIPANTS: Surveys were administered to a convenience sample of 98
      hospice providers (74 nurses, 6 physicians, 11 social workers, 7 chaplains) from
      5 Chicago-based agencies in the United States. RESULTS: Among respondents, 67%
      rated ensuring proper medication management as "most important" in hospice care
      delivery, and 33% reported frequently encountering caregivers with problems
      managing medications. To assess if caregivers had problems managing medications,
      two categories of approaches emerged from the data: prospective approaches and
      retrospective warning signs when a problem occurred (e.g. identifying medication
      nonadherence after observing a sudden patient health decline). Overall, 42%
      reported using at least one prospective approach, while 38% reported only
      retrospective signs. To help caregivers manage medications, three categories of
      approaches emerged: teaching to increase knowledge, supporting existing or
      simplifying medication management process, and counseling to overcome attitudinal
      barriers. Overall, 6% reported approaches from all three categories. About 28%
      frequently experienced difficulty teaching/supporting caregivers with medication
      management. As much as 47% believed that they would benefit "to a great extent"
      from additional resources to help caregivers. CONCLUSIONS: Supporting caregivers
      in medication management is considered important, yet challenging, to hospice
      providers. Additional resources may be needed to help providers consistently and
      effectively teach, support, and assess caregivers' medication management.

PMID- 23175510
TI  - Influences on the decision to prescribe or administer anticholinergic drugs to
      treat death rattle: a focus group study.
AB  - BACKGROUND: The evidence supporting pharmacological treatment of death rattle is
      poor; yet, anticholinergic drugs feature in end-of-life care pathways and
      guidelines worldwide as a treatment option. AIM: This qualitative arm of a wider
      study aimed to explore important issues which health-care professionals
      associated with decision-making to prescribe or administer anticholinergics at
      the end of life. DESIGN: After purposive sampling, five focus groups were
      conducted. Discussions were audiotaped and transcribed verbatim. SETTING: Thirty
      medical and nursing personnel working in inpatient and community settings from
      two specialist palliative care units in the United Kingdom took part in the
      study. RESULTS: Thematic analysis of transcripts from audiotapes revealed
      perceived pressures to prescribe and/or administer anticholinergics from
      colleagues and carers, and drugs were often prescribed or administered in order
      to be seen to 'do something', although the benefit in terms of therapeutic
      response was considered minimal. Familiarity with drug regimens and dosing was
      often based on personal experience. The monitoring of side effects of
      anticholinergics at the end of life was recognised as problematic and had little
      influence on prescribing and administration. There was also an indication that
      patients and carers in the community were more likely to receive timely verbal
      preparation and explanation around death rattle than those cared for in an
      inpatient setting. CONCLUSION: The study raises questions about the routine
      inclusion of anticholinergic treatment in UK end of life care pathways for the
      treatment of death rattle.

PMID- 23175511
TI  - Off-label prescribing in palliative care: a survey of independent prescribers.
AB  - BACKGROUND: The 'off-label' use of a drug beyond the specifications of its
      Marketing Authorization is widespread in palliative care.It is legal, but there
      are implications for prescribers, outlined by regulatory bodies such as the
      General Medical Council. A previous survey suggested that few doctors in
      palliative medicine always follow these recommendations. AIM: To obtain a
      contemporary view of how medical and non-medical independent prescribers adhere
      to current regulatory guidance. DESIGN: Selected doctor, nurse and all pharmacist
      members of www.palliativedrugs.com from the United Kingdom were invited to
      complete an online questionnaire. There were 332 respondents, a response rate of
      9% based on number of e-mails delivered. Most worked within an inpatient hospice,
      although for nurses it was the community; there was a wide range of experience.
      RESULTS: Few respondents (15%) reported that their services operated a policy on
      providing information about off-label use. Most (65%) would always make a clear
      record of the drug prescribed, and this was highest for doctors, with 39%-73%
      always operating in line with the 'must do' aspects of General Medical Council
      guidance. This proportion was lower for nurse (42%-55%) and pharmacist (0%-30%)
      responders in part because their guidance is based on the previous, less
      pragmatic General Medical Council guidance. Examples given for off-label use,
      together with general comments, provided additional insight into respondents'
      practice. CONCLUSIONS: Compared to before and to nurse and pharmacist
      prescribers, doctors appear better able to adhere to their regulatory body
      guidance. Given that all the independent prescribers in palliative care can
      prescribe the same drugs, consistent regulatory guidance is required.

PMID- 23175512
TI  - An educational package that supports laycarers to safely manage breakthrough
      subcutaneous injections for home-based palliative care patients: development and
      evaluation of a service quality improvement.
AB  - BACKGROUND: Palliative care services strive to support people to live and die
      well in their chosen environment, with optimal symptom control and a pattern of
      care supportive of laycarers. The likelihood of patients remaining at home often
      depends upon laycarers, who may be required to manage subcutaneous medications.
      AIM AND DESIGN: This study reports the development, trial and evaluation of a
      package that teaches laycarers to manage subcutaneous medications used for
      symptom control in home-based patients. The package was developed by palliative
      care stakeholders and comprises an educational session, delivered by nurses, and
      a range of demonstrative, audiovisual and written resources.
      SETTINGS/PARTICIPANTS: The package was trialled across 24 sites and was evaluated
      by 76 laycarers (pre- and post-use) and 53 nurses (at study completion). RESULTS:
      Outcomes of primary interest were perceived global usefulness of the package and
      rated relevance of components. Laycarers and nurses rated the usefulness and
      relevance of the package highly - all means were above 5 on a 7-point scale.
      Also, laycarers were invited to comment on the package, and three focus groups
      for 26 nurses explored post hoc issues following package implementation.
      CONCLUSIONS: In terms of the palliative patient's illness trajectory, consensus
      was that the time for package introduction depended upon each particular clinical
      situation and laycarer. Nursing opinion was divided concerning whether it is safe
      and appropriate for laycarers to manage subcutaneous injections. Nevertheless,
      this study demonstrates that the package supports laycarers to manage
      subcutaneous medications. This has important implications for families, services
      and health-care systems.

PMID- 23175513
TI  - Neuropathic cancer pain: prevalence, severity, analgesics and impact from the
      European Palliative Care Research Collaborative-Computerised Symptom Assessment
      study.
AB  - BACKGROUND: Neuropathic pain causes greater pain intensity and worse quality of
      life than nociceptive pain. There are no published data that confirm this in the
      cancer population. AIM: We hypothesised that patients with neuropathic cancer
      pain had more intense pain, experienced greater suffering and were treated with
      more analgesics than those with nociceptive cancer pain, and a neuropathic pain
      screening tool, painDETECT, would perform as well in those with cancer pain as is
      reported in those with non-cancer pain. DESIGN: The data were obtained from an
      international cross-sectional observational study. SETTING/PARTICIPANTS: A total
      of 1051 patients from inpatients and outpatients, with incurable cancer completed
      a computerised assessment on symptoms, function and quality of life. In all, 17
      centres within eight countries participated. Medical data were recorded by
      physicians. Pain type was a clinical diagnosis recorded on the Edmonton
      Classification System for Cancer Pain. RESULTS: Of the patients, 670 had pain:
      534 with nociceptive pain, 113 with neuropathic pain and 23 were unclassified.
      Patients with neuropathic cancer pain were significantly more likely to be
      receiving oncological treatment, strong opioids and adjuvant analgesia and have a
      reduced performance status. They reported worse physical, cognitive and social
      function. Sensitivity and specificity of painDETECT for identifying neuropathic
      cancer pain was less accurate than when used in non-cancer populations.
      CONCLUSIONS: Neuropathic cancer pain is associated with a negative impact on
      daily living and greater analgesic requirements than nociceptive cancer pain.
      Validated assessment methods are needed to enable early identification of
      neuropathic cancer pain, leading to more appropriate treatment and reduced burden
      on patients.

PMID- 23175514
TI  - Prognostic indicators of 6-month mortality in elderly people with advanced
      dementia: a systematic review.
AB  - BACKGROUND: For end-of-life dementia patients, palliative care offers a better
      quality of life than continued aggressive or burdensome medical interventions. To
      provide the best care options to dementia sufferers, validated, reliable,
      sensitive, and accurate prognostic tools to identify end-of-life dementia stages
      are necessary. AIM: To identify accurate prognosticators of mortality in elderly
      advanced dementia patients consistently reported in the literature. DESIGN:
      Systematic literature review. DATA SOURCES: PubMed, Embase, and PsycINFO
      databases were searched up to September 2012. Reference lists of included studies
      were also searched. Inclusion criteria were studies measuring factors
      specifically related to 6-month outcome in patients diagnosed with dementia in
      any residential or health-care setting. RESULTS: Seven studies met the inclusion
      criteria, five of which were set in the United States and two in Israel.
      Methodology and prognostic outcomes varied greatly between the studies. All but
      one study found that Functional Assessment Staging phase 7c, currently widely
      used to assess hospice admission eligibility in the United States, was not a
      reliable predictor of 6-month mortality. The most common prognostic variables
      identified related to nutrition/nourishment, or eating habits, followed by
      increased risk on dementia severity scales and comorbidities. CONCLUSIONS:
      Although the majority of studies agreed that the Functional Assessment Staging 7c
      criterion was not a reliable predictor of 6-month mortality, we found a lack of
      prognosticator concordance across the literature. Further studies are essential
      to identify reliable, sensitive, and specific prognosticators, which can be
      applied to the clinical setting and allow increased availability of palliative
      care to dementia patients.

PMID- 23175515
TI  - Epigenetics, c-Myc and aggressive B-cell lymphomas.

PMID- 23175516
TI  - Commentary: self-rated health and mortality in low income settings.

PMID- 23175517
TI  - Does self-rated health predict death in adults aged 50 years and above in India?
      Evidence from a rural population under health and demographic surveillance.
AB  - BACKGROUND: The Study on Global Ageing and Adult Health (SAGE) aims to improve
      empirical understanding of health and well-being of adults in developing
      countries. We examine the role of self-rated health (SRH) in predicting mortality
      and assess how socio-demographic and other disability measures influence this
      association. METHODS: In 2007, a shortened SAGE questionnaire was administered to
      5087 adults aged >=50 years under the Health Demographic Surveillance System in
      rural Pune district, India. Respondents rated their own health with a single
      global question on SRH. Disability and well-being were assessed using the WHO
      Disability Assessment Schedule Index, Health State Score and quality-of-life
      score. Respondents were followed up every 6 months till June 2011. Any change in
      spousal support, migration or death during follow-up was updated in the SAGE
      dataset. RESULTS: In all, 410 respondents (8%) died in the 3-year follow-up
      period. Mortality risk was higher with bad/very bad SRH [hazard ratio (HR) in
      men: 3.06, 95% confidence interval (CI): 1.93-4.87; HR in women: 1.64, 95% CI:
      0.94-2.86], independent of age, disability and other covariates. Disability
      measure (WHO Disability Assessment Schedule Index) and absence of spousal support
      were also associated with increased mortality risk. CONCLUSION: Our findings
      confirm an association between bad/very bad SRH and mortality for men,
      independent of age, socio-demographic factors and other disability measures, in a
      rural Indian population. This association loses significance in women when
      adjusted for disability. Our study highlights the strength of nesting cross
      sectional surveys within the context of the Health Demographic Surveillance
      System in studying the role of SRH and mortality.

PMID- 23175518
TI  - Breastfeeding and brain structure in adolescence.
AB  - BACKGROUND: The purpose of this investigation was to evaluate an association
      between duration of exclusive breastfeeding and structure of cortical regions
      implicated in general intelligence. METHODS: We studied adolescents (n = 571;
      aged 12-18 years) participating in the Saguenay Youth Study; half of the
      participants were exposed to maternal cigarette smoking during pregnancy.
      Hierarchical linear modelling was used to assess whether breastfeeding is an
      important predictor of cortical thickness when other predictors, such as age,
      sex, parental education and exposure to maternal smoking during pregnancy, are
      also considered. Target cortical regions were identified using a meta-analysis of
      functional neuroimaging studies of cognitive abilities relevant for general
      intelligence. RESULTS: We found that duration of exclusive breastfeeding was
      associated with cortical thickness in the superior and inferior parietal lobules
      (t = 2.31, P = 0.02). We also replicated the association between breastfeeding
      and general intelligence (t = 2.69, P = 0.008). CONCLUSION: In this study, we
      showed that breastfeeding is associated with variations in the thickness of the
      parietal cortex in a community-based sample of adolescents. We also found
      association of breastfeeding duration with full scale and performance IQ, as
      observed previously.

PMID- 23175519
TI  - The multiple systems model of angry rumination.
AB  - Angry rumination is perseverative thinking about a personally meaningful anger
      inducing event and is a risk factor for aggression. This article presents a new
      model for understanding angry rumination across five levels of analysis:
      cognitive, neurobiological, affective, executive control, and behavioral. The
      type of rumination that occurs at the cognitive level moderates affective
      responding and neurobiological activation, which influences executive control and
      aggression. Angry rumination recruits brain regions implicated in cognitive
      control, emotion regulation, negative affect, physiological arousal, social
      cognition, and self-reflection on emotional states. Moreover, angry rumination
      temporarily reduces self-control, which can increase aggression. The article
      suggests a functional account of angry rumination, identifies gaps in our
      knowledge, and proposes future research directions based on hypotheses derived
      from the model.

PMID- 23175520
TI  - A critical examination of popular assumptions about the benefits and outcomes of
      monogamous relationships.
AB  - In this article, we critically examine the social institution of monogamy. First,
      we discuss the lack of an adequate and consistent definition of the construct of
      monogamy and consider how common monogamy is. Next, we address perceived benefits
      of monogamy and whether those ostensible benefits are supported by empirical
      evidence. We conclude that evidence for the benefits of monogamy relative to
      other relationship styles is currently lacking, suggesting that, for those who
      choose it, consensual non-monogamy may be a viable alternative to monogamy.
      Implications for theories of close relationships are discussed.

PMID- 23175521
TI  - Targeted inactivation of HDAC2 restores p16INK4a activity and exerts antitumor
      effects on human gastric cancer.
AB  - Aberrant regulation of histone deacetylase 2 (HDAC2) was reported for gastric
      cancers. However, responsive cancer genes in disease onset and progression are
      less understood. HDAC2 expression was studied by quantitative RT-PCR and Western
      blotting. The functional consequences of HDAC2 knockdown on cell-cycle
      regulation, programmed cell death, and gene target identification was
      investigated by flow cytometry, Western blotting, electron microscopy, anchorage
      independent colony formation, and cell migration assay and by whole-genome
      microarray. Therapeutic efficacy of HDAC2 knockdown was determined in nude mice
      with small hairpin expressing human gastric cancer cells. Epigenetic regulation
      of p16(INK4a) was studied by methylation-specific PCR and chromatin-IP to
      evidence HDAC2 or acetylated-histone-H4 binding at gene specific promoter
      sequences. HDAC2 gene and protein expression was significantly upregulated in
      different histopathologic grades of human gastric cancers and cancer cell lines.
      HDAC2 inactivation significantly reduced cell motility, cell invasion, clonal
      expansion, and tumor growth. HDAC2 knockdown-induced G(1)-S cell cycle arrest and
      restored activity of p16(INK4a) and the proapoptotic factors. This treatment
      caused PARP cleavage and hypophosphorylation of the Rb-protein, repressed
      cyclinD1, CDK4, and Bcl-2 expression and induced autophagic phenotype, that is,
      LC3B-II conversion. Some gastric tumors and cancer cells displayed p16(INK4a)
      promoter hypermethylation but treatment with 5-aza-deoxycitidine restored
      activity. With others the methylation status was unchanged. Here, chromatin-IP
      evidenced HDAC2 binding. Nonetheless, expression of p16(INK4a) was restored by
      HDAC2 knockdown with notable histone-H4-acetylation, as determined by chromatin
      IP. Thus, p16(INK4a) is regulated by HDAC2. HDAC2 is a bona fide target for novel
      molecular therapies in gastric cancers.

PMID- 23175522
TI  - Contribution of HIF-1alpha in 4E-BP1 gene expression.
AB  - The eukaryotic translation initiation factor 4E (eIF4E) is necessary for the
      translation of capped mRNAs into proteins. Cap-dependent mRNA translation can be
      however inhibited by the eIF4E-binding protein 1 (4E-BP1). The hypophosphorylated
      forms of 4E-BP1 indeed sequester eIF4E and thus block translation initiation and
      consequent protein synthesis. Different reports indicate that, in addition to
      hypophosphorylation, 4E-BP1 function can be also regulated at the level of
      protein expression. This is the case in contact-inhibited cells or in cells
      exposed to hypoxia. The molecular mechanisms responsible for 4E-BP1 protein
      accumulation in these conditions remain however unknown. In the present study, we
      found that 4E-BP1 gene promoter contains a hypoxia-responsive element (HRE) that
      mediates 4E-BP1 gene upregulation via the hypoxia-inducible factor-1 alpha (HIF
      1alpha) transcription factor. Gene reporter assays then revealed that the
      presence of such HRE in the promoter of 4E-BP1 gene is involved in 4E-BP1
      accumulation in contact-inhibited cells and in cells exposed to hypoxia. We also
      reveal that the TGF-beta-dependent transcription factor SMAD4 cooperates with HIF
      1alpha to fully activate 4E-BP1 gene transcription under hypoxia. These data
      therefore suggest that HIF-1alpha contributes to 4E-BP1 gene expression under
      different conditions.

PMID- 23175523
TI  - Radiation survivors: understanding and exploiting the phenotype following
      fractionated radiation therapy.
AB  - Radiation oncology modalities such as intensity-modulated and image-guided
      radiation therapy can reduce the high dose to normal tissue and deliver a
      heterogeneous dose to tumors, focusing on areas deemed at highest risk for tumor
      persistence. Clinical radiation oncology produces daily doses ranging from 1 to
      20 Gy, with tissues being exposed to 30 or more daily fractions. Hypothesizing
      the cells that survive fractionated radiation therapy have a substantially
      different phenotype than the untreated cells, which might be exploitable for
      targeting with molecular therapeutics or immunotherapy, three prostate cancer
      cell lines (PC3, DU145, and LNCaP) and normal endothelial cells were studied to
      understand the biology of differential effects of multifraction (MF) radiation of
      0.5, 1, and/or 2 Gy fraction to 10 Gy total dose, and a single dose of 5 and 10
      Gy. The resulting changes in mRNA, miRNA, and phosphoproteome were analyzed.
      Significant differences were observed in the MF radiation exposures including
      those from the 0.5 Gy MF that produces little cell killing. As expected, p53
      function played a major role in response. Pathways modified by MF include immune
      response, DNA damage, cell-cycle arrest, TGF-beta, survival, and apoptotic signal
      transduction. The radiation-induced stress response will set forth a unique
      platform for exploiting the effects of radiation therapy as "focused biology" for
      cancer treatment in conjunction with molecular targeted or immunologically
      directed therapy. Given that more normal tissue is treated, albeit to lower doses
      with these newer techniques, the response of the normal tissue may also influence
      long-term treatment outcome.

PMID- 23175525
TI  - Nicole George wins 2012 JEB Outstanding Paper Prize.

PMID- 23175524
TI  - How to pass the false-belief task before your fourth birthday.
AB  - The experimental record of the last three decades shows that children under 4
      years old fail all sorts of variations on the standard false-belief task, whereas
      more recent studies have revealed that infants are able to pass nonverbal
      versions of the task. We argue that these paradoxical results are an artifact of
      the type of false-belief tasks that have been used to test infants and children:
      Nonverbal designs allow infants to keep track of a protagonist's perspective over
      a course of events, whereas verbal designs tend to disrupt the perspective
      tracking process in various ways, which makes it too hard for younger children to
      demonstrate their capacity for perspective tracking. We report three experiments
      that confirm this hypothesis by showing that 3-year-olds can pass a suitably
      streamlined version of the verbal false-belief task. We conclude that young
      children can pass the verbal false-belief task provided that they are allowed to
      keep track of the protagonist's perspective without too much disruption.

PMID- 23175526
TI  - Sonar jamming in the field: effectiveness and behavior of a unique prey defense.
AB  - Bats and insects provide a model system for integrating our understanding of
      predator-prey ecology, animal behavior and neurophysiology. Previous field
      studies of bat-insect interactions have been limited by the technological
      challenges involved with studying nocturnal, volant animals that use ultrasound
      and engage in battles that frequently last a fraction of a second. We overcame
      these challenges using a robust field methodology that included multiple infrared
      cameras calibrated for three-dimensional reconstruction of bat and moth flight
      trajectories and four ultrasonic microphones that provided a spatial component to
      audio recordings. Our objectives were to document bat-moth interactions in a
      natural setting and to test the effectiveness of a unique prey defense - sonar
      jamming. We tested the effect of sonar jamming by comparing the results of
      interactions between bats and Grote's tiger moth, Bertholdia trigona, with their
      sound-producing organs either intact or ablated. Jamming was highly effective,
      with bats capturing more than 10 times as many silenced moths as clicking moths.
      Moths frequently combined their acoustic defense with two separate evasive
      maneuvers: flying away from the bat and diving. Diving decreased bat capture
      success for both clicking and silenced moths, while flying away did not. The
      diving showed a strong directional component, a first for insect defensive
      maneuvers. We discuss the timing of B. trigona defensive maneuvers - which
      differs from that of other moths - in the context of moth auditory neuroethology.
      Studying bat-insect interactions in their natural environment provides valuable
      information that complements work conducted in more controlled settings.

PMID- 23175527
TI  - Acoustic gaze adjustments during active target selection in echolocating
      porpoises.
AB  - Visually dominant animals use gaze adjustments to organize perceptual inputs for
      cognitive processing. Thereby they manage the massive sensory load from complex
      and noisy scenes. Echolocation, as an active sensory system, may provide more
      opportunities to control such information flow by adjusting the properties of the
      sound source. However, most studies of toothed whale echolocation have involved
      stationed animals in static auditory scenes for which dynamic information control
      is unnecessary. To mimic conditions in the wild, we designed an experiment with
      captive, free-swimming harbor porpoises tasked with discriminating between two
      hydrophone-equipped targets and closing in on the selected target; this allowed
      us to gain insight into how porpoises adjust their acoustic gaze in a multi
      target dynamic scene. By means of synchronized cameras, an acoustic tag and on
      target hydrophone recordings we demonstrate that porpoises employ both beam
      direction control and range-dependent changes in output levels and pulse
      intervals to accommodate their changing spatial relationship with objects of
      immediate interest. We further show that, when switching attention to another
      target, porpoises can set their depth of gaze accurately for the new target
      location. In combination, these observations imply that porpoises exert precise
      vocal-motor control that is tied to spatial perception akin to visual
      accommodation. Finally, we demonstrate that at short target ranges porpoises
      narrow their depth of gaze dramatically by adjusting their output so as to focus
      on a single target. This suggests that echolocating porpoises switch from a
      deliberative mode of sensorimotor operation to a reactive mode when they are
      close to a target.

PMID- 23175528
TI  - Strike mechanics of an ambush predator: the spearing mantis shrimp.
AB  - Ambush predation is characterized by an animal scanning the environment from a
      concealed position and then rapidly executing a surprise attack. Mantis shrimp
      (Stomatopoda) consist of both ambush predators ('spearers') and foragers
      ('smashers'). Spearers hide in sandy burrows and capture evasive prey, whereas
      smashers search for prey away from their burrows and typically hammer hard
      shelled, sedentary prey. Here, we examined the kinematics, morphology and field
      behavior of spearing mantis shrimp and compared them with previously studied
      smashers. Using two species with dramatically different adult sizes, we found
      that strikes produced by the diminutive species, Alachosquilla vicina, were
      faster (mean peak speed 5.72+/-0.91 m s(-1); mean duration 3.26+/-0.41 ms) than
      the strikes produced by the large species, Lysiosquillina maculata (mean peak
      speed 2.30+/-0.85 m s(-1); mean duration 24.98+/-9.68 ms). Micro-computed
      tomography and dissections showed that both species have the spring and latch
      structures that are used in other species for producing a spring-loaded strike;
      however, kinematic analyses indicated that only A. vicina consistently engages
      the elastic mechanism. In the field, L. maculata ambushed evasive prey primarily
      at night while hidden in burrows, striking with both long and short durations
      compared with laboratory videos. We expected ambush predators to strike with very
      high speeds, yet instead we found that these spearing mantis shrimp struck more
      slowly and with longer durations than smashers. Nonetheless, the strikes of
      spearers occurred at similar speeds and durations to those of other aquatic
      predators of evasive prey. Although counterintuitive, these findings suggest that
      ambush predators do not actually need to produce extremely high speeds, and that
      the very fastest predators are using speed to achieve other mechanical feats,
      such as producing large impact forces.

PMID- 23175529
TI  - Molecular dissection of lubeluzole use-dependent block of voltage-gated sodium
      channels discloses new therapeutic potentials.
AB  - Lubeluzole, which acts on various targets in vitro, including voltage-gated
      sodium channels, was initially proposed as a neuroprotectant. The lubeluzole
      structure contains a benzothiazole moiety [N-methyl-1,3-benzothiazole-2-amine (R
      like)] related to riluzole and a phenoxy-propranol-amine moiety [(RS)-1-(3,4
      difluorophenoxy)-3-(piperidin-1-yl)propan-2-ol (A-core)] recalling propranolol.
      Both riluzole and propranolol are efficient sodium channel blockers. We studied
      in detail the effects of lubeluzole (racemic mixture and single isomers), the
      aforementioned lubeluzole moieties, and riluzole on sodium channels to increase
      our knowledge of drug-channel molecular interactions. Compounds were tested on
      hNav1.4 sodium channels, and on F1586C or Y1593C mutants functionally expressed
      in human embryonic kidney 293 cells, using the patch-clamp technique. Lubeluzole
      blocked sodium channels with a remarkable effectiveness. No stereoselectivity was
      found. Compared with mexiletine, the dissociation constant for inactivated
      channels was ~600 times lower (~11 nM), conferring to lubeluzole a huge use
      dependence of great therapeutic value. The F1586C mutation only partially
      impaired the use-dependent block, suggesting that additional amino acids are
      critically involved in high-affinity binding. Lubeluzole moieties were modest
      sodium channel blockers. Riluzole blocked sodium channels efficiently but lacked
      use dependence, similar to R-like. F1586C fully abolished A-core use dependence,
      suggesting that A-core binds to the local anesthetic receptor. Thus, lubeluzole
      likely binds to the local anesthetic receptor through its phenoxy-propranol-amine
      moiety, with consequent use-dependent behavior. Nevertheless, compared with other
      known sodium channel blockers, lubeluzole adds a third pharmacophoric point
      through its benzothiazole moiety, which greatly enhances high-affinity binding
      and use-dependent block. If sufficient isoform specificity can be attained, the
      huge use-dependent block may help in the development of new sodium channel
      inhibitors to provide pharmacotherapy for membrane excitability disorders, such
      as myotonia, epilepsy, or chronic pain.

PMID- 23175531
TI  - Application of the analytic hierarchy process in the performance measurement of
      colorectal cancer care for the design of a pay-for-performance program in Taiwan.
AB  - OBJECTIVE: To prioritize performance measures for colorectal cancer care to
      facilitate the implementation of a pay-for-performance (PFP) system. DESIGN:
      Questionnaires survey. SETTING: Medical hospitals in Taiwan. PARTICIPANTS: Sixty
      six medical doctors from 5 November 2009 to 10 December 2009. INTERVENTION:
      Analytic hierarchy process (AHP) technique. Main outcome measure(s) Performance
      measures (two pre-treatment, six treatment related and three monitoring related)
      were used. RESULTS: Forty-eight doctors responded and returned questionnaires
      (response rate 72.7%) with surgeons and physicians contributing equally. The most
      important measure was the proportion of colorectal patients who had pre-operative
      examinations that included chest X-ray and abdominal ultrasound, computed
      tomography or MRI (global priority: 0.144), followed by the proportion of stages
      I-III colorectal cancer patients who had undergone a wide surgical resection
      documented as 'negative margin' (global priority: 0.133) and the proportion of
      colorectal cancer patients who had undergone surgery with a pathology report that
      included information on tumor size and node differentiation (global priority:
      0.116). Most participants considered that the best interval for the renewal
      indicators was 3-5 years (43.75%) followed by 5-10 years (27.08%). CONCLUSIONS:
      To design a PFP program, the AHP method is a useful technique to prioritize
      performance measures, especially in a highly specialized domain such as
      colorectal cancer care.

PMID- 23175530
TI  - Conformational dynamics of Kir3.1/Kir3.2 channel activation via delta-opioid
      receptors.
AB  - This study assessed how conformational information encoded by ligand binding to
      delta-opioid receptors (DORs) is transmitted to Kir3.1/Kir3.2 channels. Human
      embryonic kidney 293 cells were transfected with bioluminescence resonance energy
      transfer (BRET) donor/acceptor pairs that allowed us to evaluate independently
      reciprocal interactions among signaling partners. These and coimmunoprecipitation
      studies indicated that DORs, Gbetagamma, and Kir3 subunits constitutively
      interacted with one another. GalphaoA associated with DORs and Gbetagamma, but
      despite being part of the complex, no evidence of its direct association with the
      channel was obtained. DOR activation by different ligands left DOR-Kir3
      interactions unmodified but modulated BRET between DOR-GalphaoA, DOR-Gbetagamma,
      GalphaoA-Gbetagamma, and Gbetagamma-Kir3 interfaces. Ligand-induced BRET changes
      assessing Gbetagamma-Kir3.1 subunit interaction 1) followed similar kinetics to
      those monitoring the GalphaoA-Gbetagamma interface, 2) displayed the same order
      of efficacy as those observed at the DOR-Gbetagamma interface, 3) were sensitive
      to pertussis toxin, and 4) were predictive of whether a ligand could evoke
      channel currents. Conformational changes at the Gbetagamma/Kir3 interface were
      lost when Kir3.1 subunits were replaced by a mutant lacking essential sites for
      Gbetagamma-mediated activation. Thus, conformational information encoded by
      agonist binding to the receptor is relayed to the channel via structural
      rearrangements that involve repositioning of Gbetagamma with respect to DORs,
      GalphaoA, and channel subunits. Further, the fact that BRET changes at the
      Gbetagamma-Kir3 interface are predictive of a ligand's ability to induce channel
      currents points to these conformational biosensors as screening tools for
      identifying GPCR ligands that induce Kir3 channel activation.

PMID- 23175532
TI  - From coordinated care trials to medicare locals: what difference does changing
      the policy driver from efficiency to quality make for coordinating care?
AB  - The terms coordination and integration refer to a wide range of interventions,
      from strategies aimed at coordinating clinical care for individuals to
      organizational and system interventions such as managed care, which contract
      medical and support services. Ongoing debate about whether financial and
      organizational integration are needed to achieve clinical integration is evident
      in policy debates over several decades, from a focus through the 1990s on
      improving coordination through structural reform and the use of market mechanisms
      to achieve allocative efficiencies (better overall service mix) to more recent
      attention on system performance to improve coordination and quality. We examine
      this shift in Australia and ask how has changing the policy driver affected
      efforts to achieve coordination? Care planning, fund pooling and purchasing are
      still important planks in coordination. Evidence suggests that financial
      strategies can be used to drive improvements for particular patient groups, but
      these are unlikely to improve outcomes without being linked to clinical
      strategies that support coordination through multidisciplinary teamwork, IT,
      disease management guidelines and audit and feedback. Meso level organizational
      strategies might align the various elements to improve coordination. Changing the
      policy driver has refocused research and policy over the last two decades from a
      focus on achieving allocative efficiencies to achieving quality and value for
      money. Research is yet to develop theoretical approaches that can deal with the
      implications for assessing effectiveness. Efforts need to identify intervention
      mechanisms, plausible relationships between these and their measurable outcomes
      and the components of contexts that support the emergence of intervention
      attributes.

PMID- 23175533
TI  - A qualitative exploration of patients' attitudes towards the 'Participate Inform
      Notice Know' (PINK) patient safety video.
AB  - OBJECTIVE: To explore patients' attitudes towards the PINK video, a patient
      education video aimed at encouraging hospital patients' involvement in safety
      relevant behaviours. DESIGN: Qualitative semi-structured interviews. Detailed
      field notes were taken during the interviews which were analysed using content
      analysis. SETTING: One National Health System (NHS) teaching hospital based in
      London, UK. PARTICIPANTS: Thirty-six in-patients aged between 20 and 79 years, 18
      of them males. INTERVENTION: The PINK video is a short animated educational video
      aimed at encouraging patients to be involved in the safety of their care during
      hospitalization. MAIN OUTCOME MEASURES: Patients' perceptions of how informative,
      relevant and acceptable the video is; attitudes towards participating in the
      recommended safety-related behaviours and; potential negative side effects of
      watching the video. RESULTS: Overall the video was received favourably among the
      interviewees. Commonly cited benefits included raising awareness and facilitating
      patients to be involved in their care during their hospital stay. More
      variability was found in participants' views with regard to the video's role as a
      patient safety enhancement tool. A number of suggestions for improvement of the
      video were provided relating to tailoring its content and design to meet the
      needs of individual patients and their circumstances. CONCLUSIONS: Educational
      videos such as PINK have significant potential to empower patients in the safety
      and quality of their care. However, efforts to implement patient safety
      educational videos in practice need to consider different patient groups' needs
      and characteristics instead of trying to adopt 'a one size fits all' approach.

PMID- 23175534
TI  - Developing mental health-care quality indicators: toward a common framework.
AB  - OBJECTIVE: Inconsistent performance measurement schemes hinder attempts to make
      international comparisons about mental health-care quality. This report describes
      a project undertaken by an international collaborative group that aims to develop
      a common framework of measures that will allow for international comparisons of
      mental health system performance. DESIGN: Representatives from each country
      submitted reports of quality measurement initiatives in mental health. Indicators
      were reviewed, and all measurable indicators were compiled and organized. Sample
      Twenty-nine programs from 11 countries and two cross-national programs submitted
      reports. METHODS: Indicators were evaluated according to measurable inclusion
      criteria. RESULTS: These methods yielded 656 total measures that were organized
      into 17 domains and 80 subdomains. CONCLUSIONS: No single program contained
      indicators in all domains, highlighting the need for a comprehensive, shared
      scheme for international measurement. By collecting and organizing measures
      through an inductive compilation of existing programs, the present study has
      generated a maximally inclusive basis for the creation of a common framework of
      international mental health quality indicators.

PMID- 23175535
TI  - Development of the Chinese primary care assessment tool: data quality and
      measurement properties.
AB  - OBJECTIVE: The aim of this study was to translate and adapt the Primary Care
      Assessment Tool to assess the perceptions of the quality of primary care among
      patients in China and to examine the psychometric properties of the adapted
      Primary Care Assessment Tool Chinese version (PCAT-C). DESIGN: A cross-sectional
      survey to assess the validity and reliability of PCAT-C using standard
      psychometric techniques. SETTING: Outpatient departments of five state-level and
      provincial-level hospitals and four municipal-level hospitals as well as nine
      community health centers in Changsha, China. PARTICIPANTS: A total of 2532
      patients visiting primary care providers. RESULTS: The PCAT-C was acceptable to
      patients, as evidenced by low proportions of missing data and a full range of
      possible scores for all items. Two items were eliminated following principal
      component analysis and reliability testing. The principal component analysis
      extracted eight multiple-item scales and one single-item scale. Multiple-item
      scales had reasonable internal consistency and high item-scale correlations.
      CONCLUSIONS: This study represents the first attempt to construct an instrument
      for assessing patient reports on the quality of primary care, which is applicable
      to the Chinese context. Psychometric assessments indicated that the PCAT-C is a
      useful instrument for assessing the core attributes of primary care in China.

PMID- 23175536
TI  - Is N-feedback involved in the inhibition of nitrogen fixation in drought-stressed
      Medicago truncatula?
AB  - Drought stress is a major factor limiting nitrogen fixation (NF) in crop
      production. However, the regulatory mechanism involved and the origin of the
      inhibition, whether local or systemic, is still controversial and so far scarcely
      studied in temperate forage legumes. Medicago truncatula plants were
      symbiotically grown with a split-root system and exposed to gradual water
      deprivation. Physiological parameters, NF activity, and amino acid content were
      measured. The partial drought treatment inhibited NF in the nodules directly
      exposed to drought stress. Concomitantly, in the droughted below-ground organs,
      amino acids accumulated prior to any drop in evapotranspiration (ET). It is
      concluded that drought exerts a local inhibition of NF and drives an overall
      accumulation of amino acids in diverse plant organs which is independent of the
      decrease in ET. The general increase in the majority of single amino acids in the
      whole plant questions the commonly accepted concept of a single amino acid acting
      as an N-feedback signal.

PMID- 23175537
TI  - Living in the in-between: families caring for a child with a progressive
      neurodegenerative illness.
AB  - Medical advances in recent years have led to an increased life span for children
      with progressive, neurodegenerative illnesses. The purpose of this hermeneutic
      inquiry was to explore the experience of families caring for their child at home.
      In-depth, audiorecorded interviews with six families (13 interviews) living in
      western Canada were transcribed and analyzed. The illness journey was revealed to
      be complex and unpredictable. We discovered many metaphors that spoke to the
      child's/family's life and explored the paradox of duality, such as holding both
      joy and sorrow, and containing both suffering and love. We outline implications
      for policy development within the area of respite care and coordination of
      services for families. The voices of families must be a vital component to
      influence and guide education and service development within the emerging
      specialty of pediatric palliative care.

PMID- 23175540
TI  - Size-specific dose estimation for CT: how should it be used and what does it
      mean?

PMID- 23175539
TI  - Science to practice: a new insight into nephrotoxicity after contrast medium
      administration.
AB  - Liu et al (1) have shown that iodinated contrast medium preferentially
      vasoconstricts the glomerular afferent arterioles by depleting endothelial nitric
      oxide bioavailability. This potentiates an exaggerated afferent arteriolar
      vasoconstricting response to angiotensin II and opens possibilities for new
      methods to prevent or treat nephrotoxicity after contrast medium administration.

PMID- 23175541
TI  - Updated relevance of mammographic screening modalities in women previously
      treated with chest irradiation for Hodgkin disease.

PMID- 23175542
TI  - Multidetector CT of blunt abdominal trauma.
AB  - The morbidity, mortality, and economic costs resulting from trauma in general,
      and blunt abdominal trauma in particular, are substantial. The "panscan"
      (computed tomographic [CT] examination of the head, neck, chest, abdomen, and
      pelvis) has become an essential element in the early evaluation and decision
      making algorithm for hemodynamically stable patients who sustained abdominal
      trauma. CT has virtually replaced diagnostic peritoneal lavage for the detection
      of important injuries. Over the past decade, substantial hardware and software
      developments in CT technology, especially the introduction and refinement of
      multidetector scanners, have expanded the versatility of CT for examination of
      the polytrauma patient in multiple facets: higher spatial resolution, faster
      image acquisition and reconstruction, and improved patient safety (optimization
      of radiation delivery methods). In this article, the authors review the elements
      of multidetector CT technique that are currently relevant for evaluating blunt
      abdominal trauma and describe the most important CT signs of trauma in the
      various organs. Because conservative nonsurgical therapy is preferred for all but
      the most severe injuries affecting the solid viscera, the authors emphasize the
      CT findings that are indications for direct therapeutic intervention.

PMID- 23175544
TI  - Histogram analysis of whole-lesion enhancement in differentiating clear cell from
      papillary subtype of renal cell cancer.
AB  - PURPOSE: To compare histogram analysis of voxel-based whole-lesion (WL)
      enhancement to qualitative assessment and region-of-interest (ROI)-based
      enhancement analysis in discriminating the renal cell cancer (RCC) subtype clear
      cell RCC (ccRCC) from papillary RCC (pRCC). MATERIALS AND METHODS: In this
      institutional review board-approved, HIPAA-compliant retrospective study, 73
      patients underwent magnetic resonance (MR) imaging prior to surgery for RCC
      between January 2007 and January 2010. Three-dimensional fat-suppressed T1
      weighted gradient-echo corticomedullary phase acquisitions, obtained before and
      after contrast agent administration, were transferred to a workstation at which
      automated registration followed by semiautomated segmentation of the RCC was
      performed. Percent enhancement was computed on a per-voxel basis: (SI(post) -
      SI(pre))/SI(pre) .100, where SI(pre) and SI(post) indicate signal intensity
      before and after contrast enhancement, respectively. The WL quantitative
      parameters of mean, median, and third quartile enhancement and histogram
      distribution parameters kurtosis and skewness were computed for each lesion. WL
      enhancement parameters were compared with ROI-based analysis and qualitative
      assessment with regards to diagnostic accuracy and interreader agreement in
      differentiating ccRCC from pRCC. RESULTS: There were 19 pRCCs and 55 ccRCCs at
      pathologic examination. ccRCC had significantly higher WL mean, median, and third
      quartile enhancement compared with pRCC and hade significantly lower kurtosis and
      skewness (all P < .001). Third quartile enhancement had the highest accuracy
      (94.6%; area under the curve, 0.980) in discriminating ccRCC from pRCC, which was
      significantly higher than the accuracy of qualitative assessment (86.0%; P = .04)
      but not significantly higher than that of ROI enhancement (89.2%; P = .52). WL
      enhancement parameters had higher interreader agreement (kappa = 0.91-1.0)
      compared with ROI enhancement or qualitative assessment (kappa = 0.83 and 0.7,
      respectively) in discriminating ccRCC from pRCC. CONCLUSION: WL enhancement
      histogram analysis is feasible and can potentially be used to differentiate ccRCC
      from pRCC with high accuracy. SUPPLEMENTAL MATERIAL:
      http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.12111281/-/DC1.

PMID- 23175543
TI  - Hypervascular hepatocellular carcinoma: correlation between biologic features and
      signal intensity on gadoxetic acid-enhanced MR images.
AB  - PURPOSE: To analyze the correlation among biologic features, tumor marker
      production, and signal intensity at gadoxetic acid-enhanced MR imaging in
      hepatocellular carcinomas (HCCs). MATERIALS AND METHODS: Institutional ethics
      committee approval and informed consent were obtained for this retrospective
      study. From April 2008 to September 2011, 180 surgically resected HCCs in 180
      patients (age, 65.0 years +/- 10.3 [range, 34-83 years]; 138 men, 42 women) were
      classified as either hypointense (n = 158) or hyperintense (n = 22) compared with
      the signal intensity of the background liver on hepatobiliary phase gadoxetic
      acid-enhanced MR images. Pathologic features were analyzed and a fetoprotein
      (AFP) and protein induced by vitamin K absence or antagonist-II (PIVKA-II)
      production were compared by means of serum analysis and immunohistochemical
      staining. Recurrence and survival rates were also evaluated. The Mann-Whitney and
      Pearson correlation tests were used for statistical analysis. RESULTS: The grade
      of differentiation was higher (P = .028) and portal vein invasion was less
      frequent in hyperintense HCCs (13.6%) than in hypointense HCCs (36.7%) (P =
      .039). The serum levels of AFP, Lens culinaris agglutinin reactive fraction of
      AFP, and PIVKA-II were lower in hyperintense than in hypointense HCCs (P = .003,
      .004, and .026, respectively). Immunohistochemical AFP and PIVKA-II expression
      were lower in hyperintense than in hypointense HCCs (both P < .001). The
      recurrence rate was lower in hyperintense than in hypointense HCCs (P = .039).
      CONCLUSION: The results suggest that hyperintense HCCs on gadoxetic acid-enhanced
      MR images are less aggressive than hypointense HCCs. SUPPLEMENTAL MATERIAL:
      http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.12120226/-/DC1.

PMID- 23175545
TI  - Findings of the UK national audit evaluating image-guided or image-assisted liver
      biopsy. Part I. Procedural aspects, diagnostic adequacy, and accuracy.
AB  - PURPOSE: To assess procedural aspects, diagnostic adequacy, and accuracy of liver
      biopsy across the United Kingdom. MATERIALS AND METHODS: Institutional review
      board approval for this type of study is not required in the United Kingdom. All
      radiology departments with an approved leader for departmental audit registered
      with the Royal College of Radiologists were invited to participate in this
      retrospective audit. The first 50 consecutive patients who underwent image-guided
      or image-assisted liver biopsy in 2008 were included. Audit standards relating to
      procedural aspects of biopsy, sample adequacy, and accuracy were prepared with
      reference to published data. Sensitivity, specificity, positive and negative
      likelihood ratios, and accuracy were calculated. Organizational and clinical
      variables were investigated for their association with diagnostic specimen
      quality. RESULTS: Eighty-seven (41%) of 210 departments supplied data for this
      study, with a total of 3496 cases (1225 focal disease, 2262 nonfocal disease,
      nine unspecified). Ultrasonographic (US) guidance was the technique most commonly
      used for focal lesions and for cases of nonfocal disease (2808 [96.38%] of 3490
      cases). The audit standard for sample adequacy (98%) was narrowly missed in
      practice (3401 [97.96%] of 3472 cases); however, the standard for diagnostic
      accuracy (90%) was met (3187 [98.55%] of 3234 cases). Poor compliance with
      postbiopsy documentation was observed. CONCLUSION: The majority of liver biopsies
      in this audit were performed by radiologists using image guidance or assistance,
      usually in the form of US. Biopsies were performed with a high degree of
      accuracy. Some postprocedural aspects of biopsy failed to meet required standards
      and would merit reaudit after practice changes. SUPPLEMENTAL MATERIAL:
      http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.12111562/-/DC1.

PMID- 23175546
TI  - Default-mode network disruption in mild traumatic brain injury.
AB  - PURPOSE: To investigate the integrity of the default-mode network (DMN) by using
      independent component analysis (ICA) methods in patients shortly after mild
      traumatic brain injury (MTBI) and healthy control subjects, and to correlate DMN
      connectivity changes with neurocognitive tests and clinical symptoms. MATERIALS
      AND METHODS: This study was approved by the institutional review board and
      complied with HIPAA regulations. Twenty-three patients with MTBI who had
      posttraumatic symptoms shortly after injury (<2 months) and 18 age-matched
      healthy control subjects were included in this study. Resting-state functional
      magnetic resonance imaging was performed at 3 T to characterize the DMN by using
      ICA methods, including a single-participant ICA on the basis of a comprehensive
      template from core seeds in the posterior cingulate cortex (PCC) and medial
      prefrontal cortex (MPFC) nodes. ICA z images of DMN components were compared
      between the two groups and correlated with neurocognitive tests and clinical
      performance in patients by using Pearson and Spearman rank correlation. RESULTS:
      When compared with the control subjects, there was significantly reduced
      connectivity in the PCC and parietal regions and increased frontal connectivity
      around the MPFC in patients with MTBI (P < .01). These frontoposterior opposing
      changes within the DMN were significantly correlated (r = -0.44, P = .03). The
      reduced posterior connectivity correlated positively with neurocognitive
      dysfunction (eg, cognitive flexibility), while the increased frontal connectivity
      correlated negatively with posttraumatic symptoms (ie, depression, anxiety,
      fatigue, and postconcussion syndrome). CONCLUSION: These results showed abnormal
      DMN connectivity patterns in patients with MTBI, which may provide insight into
      how neuronal communication and information integration are disrupted among DMN
      key structures after mild head injury.

PMID- 23175547
TI  - Iliac vein compression as risk factor for left- versus right-sided deep venous
      thrombosis: case-control study.
AB  - PURPOSE: To determine if compression of the left common iliac vein (LCIV) by the
      right common iliac artery is associated with left-sided deep venous thrombosis
      (DVT). MATERIALS AND METHODS: This institutional review board-approved case
      control study was performed in a cohort of 230 consecutive patients (94 men, 136
      women; mean age, 57.5 years; range, 10-94 years) at one institution who had
      undergone contrast material-enhanced computed tomography of the pelvis prior to a
      diagnosis of unilateral DVT. Demographic data and information on risk factors
      were collected. Two board-certified radiologists determined iliac vein
      compression by using quantitative measures of percentage compression {[1 minus
      (LCIV diameter at point of maximal compression/distal right common iliac vein
      diameter)] times 100%}, as well as qualitative measures (none, mild, moderate,
      severe), with estimates of measurement variability. Logistic regression analysis
      was performed (independent variable, left vs right DVT; dependent variable, iliac
      vein compression). Cutpoints of relevant compression were evaluated by using
      splines. Means (with 95% confidence intervals [CIs]) and odds ratios (ORs) (and
      95% CIs) of left DVT per 1% increase in percentage compression were calculated.
      RESULTS: Patients with right DVT were more likely than those with left DVT to
      have a history of pulmonary embolism. Overall, in all study patients, mean
      percentage compression was 36.6%, 66 (29.7%) of 222 had greater than 50%
      compression, and 16 (7.2%) had greater than 70% compression. At most levels of
      compression, increasing compression was not associated with left DVT (adjusted
      ORs, 1.00, 0.99, 1.02) but above 70%, LCIV compression may be associated with
      left DVT (adjusted ORs, 3.03, 0.91, 10.15). CONCLUSION: Increasing levels of
      percentage compression were not associated with left-sided DVT up to 70%;
      however, greater than 70% compression may be associated with left DVT.
      SUPPLEMENTAL MATERIAL:
      http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.12111580/-/DC1.

PMID- 23175549
TI  - Case 188: Intravenous leiomyomatosis with intracaval and intracardiac
      involvement.

PMID- 23175550
TI  - The Lazarus syndrome and the ethics of evidence-based versus experience-based
      medicine.

PMID- 23175551
TI  - Efficacy of hydration in the prevention of contrast material-induced nephropathy.

PMID- 23175552
TI  - Contrast material-induced nephropathy in the era of hydration.

PMID- 23175553
TI  - Fat-poor angiomyolipoma and renal cell carcinoma: differentiation with MR imaging
      and accuracy of histopathologic evaluation.

PMID- 23175554
TI  - Direct observation therapy-plus can prevent acquired resistance to
      fluoroquinolones among patients with multidrug-resistant tuberculosis in Taiwan.

PMID- 23175556
TI  - Effect of high-dose or split-dose artesunate on parasite clearance in artemisinin
      resistant falciparum malaria.
AB  - BACKGROUND: The emergence of Plasmodium falciparum resistance to artemisinins on
      the Cambodian and Myanmar-Thai borders poses severe threats to malaria control.
      We investigated whether increasing or splitting the dose of the short-half-life
      drug artesunate improves parasite clearance in falciparum malaria in the 2
      regions. METHODS: In Pailin, western Cambodia (from 2008 to 2010), and Wang Pha,
      northwestern Thailand (2009-2010), patients with uncomplicated falciparum malaria
      were randomized to oral artesunate 6 mg/kg/d as a once-daily or twice-daily dose
      for 7 days, or artesunate 8 mg/kg/d as a once-daily or twice-daily dose for 3
      days, followed by mefloquine. Parasite clearance and recrudescence for up to 63
      days of follow-up were assessed. RESULTS: A total of 159 patients were enrolled.
      Overall median (interquartile range [IQR]) parasitemia half-life (half-life) was
      6.03 (4.89-7.28) hours in Pailin versus 3.42 (2.20-4.85) hours in Wang Pha (P =
      .0001). Splitting or increasing the artesunate dose did not shorten half-life in
      either site. Pharmacokinetic profiles of artesunate and dihydroartemisinin were
      similar between sites and did not correlate with half-life. Recrudescent
      infections occurred in 4 of 79 patients in Pailin and 5 of 80 in Wang Pha and was
      not different between treatment arms (P = .68). CONCLUSIONS: Increasing the
      artesunate treatment dose up to 8 mg/kg/d or splitting the dose does not improve
      parasite clearance in either artemisinin resistant or more sensitive infections
      with P. falciparum. Clinical Trials Registration. ISRCTN15351875.

PMID- 23175557
TI  - Editorial commentary: single-dose primaquine as gametocytocidal treatment in
      patients with uncomplicated falciparum malaria.

PMID- 23175555
TI  - Assessment, diagnosis, and treatment of HIV-associated neurocognitive disorder: a
      consensus report of the mind exchange program.
AB  - Many practical clinical questions regarding the management of human
      immunodeficiency virus (HIV)-associated neurocognitive disorder (HAND) remain
      unanswered. We sought to identify and develop practical answers to key clinical
      questions in HAND management. Sixty-six specialists from 30 countries provided
      input into the program, which was overseen by a steering committee. Fourteen
      questions were rated as being of greatest clinical importance. Answers were
      drafted by an expert group based on a comprehensive literature review. Sixty
      three experts convened to determine consensus and level of evidence for the
      answers. Consensus was reached on all answers. For instance, good practice
      suggests that all HIV patients should be screened for HAND early in disease using
      standardized tools. Follow-up frequency depends on whether HAND is already
      present or whether clinical data suggest risk for developing HAND. Worsening
      neurocognitive impairment may trigger consideration of antiretroviral
      modification when other causes have been excluded. The Mind Exchange program
      provides practical guidance in the diagnosis, monitoring, and treatment of HAND.

PMID- 23175559
TI  - Editorial commentary: children with HIV in low-prevalence settings: finding the
      needle in a Haystack.

PMID- 23175558
TI  - Mortality and treatment outcomes of China's National Pediatric antiretroviral
      therapy program.
AB  - BACKGROUND: The aim of this study was to describe 3-year mortality rates,
      associated risk factors, and long-term clinical outcomes of children enrolled in
      China's national free pediatric antiretroviral therapy (ART) program. METHODS:
      Records were abstracted from the national human immunodeficiency virus (HIV)/AIDS
      case reporting and national pediatric ART databases for all HIV-positive children
      <=15 years old who initiated ART prior to December 2010. Mortality risk factors
      over 3 years of follow-up were examined using Cox proportional hazards regression
      models. Life tables were used to determine survival rate over time. Longitudinal
      plots of CD4(+) T-cell percentage (CD4%), hemoglobin level, weight-for-age z
      (WAZ) score, and height-for-age z (HAZ) score were created using generalized
      estimating equation models. RESULTS: Among the 1818 children included in our
      cohort, 93 deaths were recorded in 4022 child-years (CY) of observed time for an
      overall mortality rate of 2.31 per 100 CY (95% confidence interval [CI], 1.75
      2.78). The strongest factor associated with mortality was baseline WAZ score <-2
      (adjusted hazard ratio [HR] = 9.1; 95% CI, 2.5-33.2), followed by World Health
      Organization stage III or IV disease (adjusted HR = 2.4; 95% CI, 1.1-5.2), and
      hemoglobin <90 g/L (adjusted HR = 2.2; 95% CI, 1.2-3.9). CD4%, hemoglobin level,
      WAZ score, and HAZ score increased over time. CONCLUSIONS: Our finding that 94%
      of children engaged in this program are still alive and of improved health after
      3 years of treatment demonstrates that China's national pediatric ART program is
      effective. This program needs to be expanded to better meet treatment demands,
      and efforts to identify HIV-positive children earlier must be prioritized.

PMID- 23175560
TI  - Impact of the 7-valent pneumococcal conjugate vaccine on invasive pneumococcal
      disease in infants younger than 90 days in England and wales.
AB  - BACKGROUND: Streptococcus pneumoniae is an uncommon but well-recognized cause of
      invasive bacterial disease in young infants. This study aimed to determine the
      impact of the 7-valent pneumococcal conjugate vaccine (PCV7) on invasive
      pneumococcal disease (IPD) in infants aged <90 days in England and Wales and
      describe their clinical characteristics following PCV7 introduction. METHODS:
      Trends in IPD among infants aged <90 days during 1998-1999 through 2009-2010 were
      analyzed using enhanced national surveillance data. Following PCV7 introduction,
      clinical information was also obtained for IPD cases in the birth cohorts
      eligible for vaccination. RESULTS: Prior to PCV7 introduction, IPD incidence in
      infants aged <90 days was 13.0 (95% confidence interval [CI], 12.0-14.0) per 100
      000 live births and PCV7 serotypes accounted for 44% (154/349) of serotyped
      isolates. PCV7 introduction resulted in 83% (95% CI, 66%-91%, P < .001) reduction
      in PCV7 IPD and a declining trend in overall IPD by 2009-2010. Of the 256 cases
      diagnosed after PCV7 introduction, 23% (n = 60) had been born before 37 weeks'
      gestation. A third of cases (84/256, 33%) developed IPD in the first 48 hours of
      life, where 42% (35/84) were premature. Meningitis was diagnosed in 94 infants
      (37%) and its prevalence increased with age. Case fatality was 7% (18/256) and
      was higher for meningitis than nonmeningitis cases (adjusted odds ratio, 3.8 [95%
      CI, 1.2-12.0], P = .024). CONCLUSIONS: Young infants have benefited from PCV7
      through indirect (herd) protection. Given that a third of cases occurred within
      48 hours of birth, further studies should focus on risk factors for IPD in
      pregnancy and strategies to prevent mother-to-child transmission.

PMID- 23175562
TI  - Fungal infections in immunocompromised travelers.
AB  - Immunocompromised patients represent an increasing group of travelers, for
      business, tourism, and visiting friends and relatives. Those with severe cellular
      immunodeficiency (advanced human immunodeficiency virus infection and transplant
      recipients) display the highest risk of fungal infections. International travel
      is less risky in most other types of immunodeficiency (except those with
      neutropenia). A systematic visit in a travel clinic for immunocompromised
      patients traveling to the tropics ensures that the specific risks of acquiring
      fungal infections (and others) are understood. When immunocompromised hosts
      return to their area of residence, a nonbacteriologically documented, potentially
      severe, febrile pneumonia, with or without dissemination signs (skin lesions,
      cytopenia) should alert for travel-acquired fungal infection, even years after
      return. Localized subcutaneous nodule may be also ascribed to fungal infection.
      Finally, infectious diseases physicians should be aware of major clinical
      patterns of travel-acquired fungal infection, as well as the fungi involved, and
      risk factors according to the geographical area visited.

PMID- 23175561
TI  - Efficacy of mefloquine intermittent preventive treatment in pregnancy against
      Schistosoma haematobium infection in Gabon: a nested randomized controlled
      assessor-blinded clinical trial.
AB  - BACKGROUND: Urogenital schistosomiasis is a major public health problem in sub
      Saharan Africa, and routine programs for screening and treatment of pregnant
      women are not established. Mefloquine-currently evaluated as a potential
      alternative to sulfadoxine-pyrimethamine as intermittent preventive treatment
      against malaria in pregnancy (IPTp)-is known to exhibit activity against
      Schistosoma haematobium. In this study we evaluated the efficacy of mefloquine
      IPTp against S. haematobium infection in pregnant women. METHODS: Pregnant women
      with S. haematobium infection presenting at 2 antenatal health care centers in
      rural Gabon were invited to participate in this nested randomized controlled,
      assessor-blinded clinical trial comparing sulfadoxine-pyrimethamine with
      mefloquine IPTp. Study drugs were administered twice during pregnancy with a 1-
      month interval after completion of the first trimester. RESULTS: Sixty-five
      pregnant women were included in this study. Schistosoma haematobium egg excretion
      rates showed a median reduction of 98% (interquartile range [IQR], 70%-100%) in
      the mefloquine group compared to an increase of 20% (IQR, -186% to 75%) in the
      comparator group. More than 80% of patients showed at least 50% reduction of egg
      excretion and overall cure rate was 47% (IQR, 36%-70%) 6 weeks after the second
      administration of mefloquine IPTp. CONCLUSION: When used as IPTp for the
      prevention of malaria, mefloquine shows promising activity against concomitant S.
      haematobium infection leading to an important reduction of egg excretion in
      pregnant women. Provided that further studies confirm these findings, the use of
      mefloquine may transform future IPTp programs into a 2-pronged intervention
      addressing 2 of the most virulent parasitic infections in pregnant women in sub
      Saharan Africa. CLINICAL TRIALS REGISTRATION: NCT01132248; ATMR2010020001429343.

PMID- 23175563
TI  - The effect of primaquine on gametocyte development and clearance in the treatment
      of uncomplicated falciparum malaria with dihydroartemisinin-piperaquine in South
      sumatra, Western indonesia: an open-label, randomized, controlled trial.
AB  - BACKGROUND: Artemisinin-based combination therapy is very effective in clearing
      asexual stages of malaria and reduces gametocytemia, but may not affect mature
      gametocytes. Primaquine is the only commercially available drug that eliminates
      mature gametocytes. METHODS: We conducted a 2-arm, open-label, randomized,
      controlled trial to evaluate the efficacy of single-dose primaquine (0.75 mg/kg)
      following treatment with dihydroartemisinin-piperaquine (DHP) on Plasmodium
      falciparum gametocytemia, in Indonesia. Patients aged >=5 years with
      uncomplicated falciparum malaria, normal glucose-6-phosphate dehydrogenase enzyme
      levels, and hemoglobin levels >=8 g/dL were assigned by computerized-generating
      sequence to a standard 3-day course of DHP alone (n = 178) or DHP combined with a
      single dose of primaquine on day 3 (n = 171). Patients were seen on days 1, 2, 3,
      and 7 and then weekly for 42 days to assess the presence of gametocytes and
      asexual parasites by microscopy. Survival analysis was stratified by the presence
      of gametocytes on day 3. RESULTS: DHP prevented development of gametocytes in 277
      patients without gametocytes on day 3. In the gametocytemic patients (n = 72),
      primaquine was associated with faster gametocyte clearance (hazard ratio = 2.42
      [95% confidence interval, 1.39-4.19], P = .002) and reduced gametocyte densities
      (P = .018). The day 42 cure rate of asexual stages in the DHP + primaquine and
      DHP-only arms were: polymerase chain reaction (PCR) unadjusted, 98.7% vs 99.4%,
      respectively; PCR adjusted, 100% for both. Primaquine was well tolerated.
      CONCLUSIONS: Addition of single-dose 0.75 mg/kg primaquine shortens the
      infectivity period of DHP-treated patients and should be considered in low
      transmission regions that aim to control and ultimately eliminate falciparum
      malaria. Clinical Trials Registration. NCT01392014.

PMID- 23175566
TI  - Human brucellosis, a heterogeneously distributed, delayed, and misdiagnosed
      disease in china.

PMID- 23175565
TI  - Listeriosis at a tertiary care hospital in beijing, china: high prevalence of
      nonclustered healthcare-associated cases among adult patients.
AB  - BACKGROUND: Listeriosis is an emerging infectious disease associated with high
      mortality. There are few published reports from East Asia and developing
      countries. Our goal was to describe the clinical characteristics and outcomes of
      patients diagnosed with Listeria monocytogenes at a tertiary care hospital in
      Beijing, China. METHODS: Peking Union Medical College Hospital (PUMCH), an 1800
      bed hospital, consists of 2 campuses that house different medical departments. We
      retrospectively reviewed all culture-proven cases of listeriosis occurring at
      PUMCH between 1999 and 2011. Point estimates and 95% confidence intervals are
      presented. RESULTS: There were 38 patients with listeriosis: 5 neonatal, 8
      maternal, and 25 nonmaternal. The median age of the adult nonmaternal patients
      was 47 (range, 18-79) years with a female predominance (72%). Forty percent (n =
      10) had an underlying rheumatic disease. Forty-four percent of cases (n = 11)
      were healthcare-associated infections occurring a median of 20 (range, 3-44) days
      after hospital admission. Only 2 of the 11 healthcare-associated cases clustered
      in space and time. One healthcare-associated case occurred in a patient receiving
      KHI-272 therapy, an oral, irreversible dual EGFR/HER2 inhibitor. The neonatal and
      maternal listeriosis cases were similar to those reported in the literature.
      CONCLUSIONS: Nonclustered healthcare-associated cases of L. monocytogenes
      occurred at a large tertiary care hospital in Beijing, China. The source of these
      infections is unclear. Although rare, in the setting of immunosuppression,
      Listeria should be considered in the differential diagnosis of healthcare
      associated infections, even in the absence of a point-source outbreak.

PMID- 23175567
TI  - Optimal Nonbipartite Matching and Its Statistical Applications.
AB  - Matching is a powerful statistical tool in design and analysis. Conventional two
      group, or bipartite, matching has been widely used in practice. However, its
      utility is limited to simpler designs. In contrast, nonbipartite matching is not
      limited to the two-group case, handling multiparty matching situations. It can be
      used to find the set of matches that minimize the sum of distances based on a
      given distance matrix. It brings greater flexibility to the matching design, such
      as multigroup comparisons. Thanks to improvements in computing power and freely
      available algorithms to solve nonbipartite problems, the cost in terms of
      computation time and complexity is low. This article reviews the optimal
      nonbipartite matching algorithm and its statistical applications, including
      observational studies with complex designs and an exact distribution-free test
      comparing two multivariate distributions. We also introduce an R package that
      performs optimal nonbipartite matching. We present an easily accessible web
      application to make nonbipartite matching freely available to general
      researchers.

PMID- 23175568
TI  - Systemic sclerosis (scleroderma) and cancer risk: systematic review and meta
      analysis of observational studies.
AB  - OBJECTIVES: A higher incidence of cancer in scleroderma patients compared with
      the general population has been suggested by several observational studies,
      reporting, however, different estimates. Therefore, we aimed to perform a
      systematic review and meta-analysis to definitely assess this association.
      METHODS: We searched MEDLINE and Embase for all original articles of
      observational studies on cancer incidence in scleroderma patients without
      language restriction published up to December 2011. Two independent authors
      reviewed all titles/abstracts and retrieved detailed full-text of potentially
      relevant articles to identify studies according to predefined selection criteria.
      Summary estimates were derived using random-effects model and reported as
      relative risk (RR). Publication bias was evaluated by trim and fill analysis.
      RESULTS: From articles initially identified, 16 original studies, involving more
      than 7000 patients, were included in the present review. Compared with the
      general population, the summary RR to develop all invasive cancers in scleroderma
      patients was 1.75 (95% CI 1.41, 2.18). The results for selected cancer sites
      indicated a strong association with lung cancer (RR 4.35; 95% CI 2.08, 9.09), and
      a significant increased risk also for haematological neoplasms (RR 2.24; 95% CI
      1.53, 3.29). The relation with breast cancer, suggested in some previous
      epidemiological studies, was not confirmed (RR 1.05; 95% CI 0.86, 1.29).
      CONCLUSION: The present meta-analysis, the first on scleroderma and cancer risk,
      provides definite estimates on the association between scleroderma and cancer.

PMID- 23175569
TI  - Validation in Spanish of a screening questionnaire for the detection of psoriatic
      arthritis in patients with psoriasis.
AB  - OBJECTIVE: A patient self-administered questionnaire [PsA Screening and
      Evaluation (PASE)] has been developed and validated in English, but has not been
      tried in Spanish speaking populations. This study aimed to adapt and validate
      PASE in Spanish to screen Spanish speaking psoriasis patients for signs and
      symptoms of inflammatory arthritis. METHODS: Initial translation from English to
      Spanish (forward translation) was performed by two independent translators and
      the resulting versions were synthesized during a consensus meeting. The
      questionnaire was tried in a pilot study and resulted in a change in the
      agreement scale for a frequency scale with wording adaptation [Spanish PASE (PASE
      S)]. RESULTS: One hundred and eleven patients were screened with PASE-S; 25 with
      PsA (without previous treatments), 23 with psoriasis, 22 with psoriasis and OA
      and 41 with OA without psoriasis. The diagnosis of psoriasis was performed by a
      dermatologist, and a rheumatologist determined the diagnosis of PsA or OA.
      Patients with PsA had statistically significant higher symptoms, function and
      total PASE-S scores compared with those without PsA. Receiver operator curves
      showed an area under the curve of 0.79 (95% CI 0.69, 0.89) for the total score. A
      cut-off value >=34 showed sensitivity of 76%, and specificity of 74.4% for the
      diagnosis of PsA. CONCLUSION: The validated PASE questionnaire is a self
      administered tool that can be used to screen for PsA among patients with
      psoriasis in a Spanish speaking population. PASE was able to distinguish between
      symptoms of PsA and OA.

PMID- 23175571
TI  - Efficient Moment Matrix Generation for Arbitrary Chemical Networks.
AB  - As stochastic simulations become increasingly common in biological research,
      tools for analysis of such systems are in demand. The deterministic analogue to
      stochastic models, a set of probability moment equations equivalent to the
      Chemical Master Equation (CME), offers the possibility of a priori analysis of
      systems without the need for computationally costly Monte Carlo simulations.
      Despite the drawbacks of the method, in particular non-linearity in even the
      simplest of cases, the use of moment equations combined with moment-closure
      techniques has been used effectively in many fields. The techniques currently
      available to generate moment equations rely upon analytical expressions that are
      not efficient upon scaling. Additionally, the resulting moment-dependent matrix
      is lower diagonal and demands massive memory allocation in extreme cases. Here it
      is demonstrated that by utilizing factorial moments and the probability
      generating function (the Z-transform of the probability distribution) a recursive
      algorithm is produced. The resulting method is scalable and particularly
      efficient when high-order moments are required. The matrix produced is banded and
      often demands substantially less memory resources.

PMID- 23175570
TI  - Sack and sugar, and the aetiology of gout in England between 1650 and 1900.
AB  - A marked increase in gout was observed in England during the 17th to 20th
      centuries. Many have ascribed this rapid increase in gout to the introduction of
      wines that were laced with lead. In this article, we suggest another likely
      contributor, which is the marked increase in sugar intake that occurred in
      England during this period. Sugar contains fructose, which raises uric acid and
      increases the risk for gout. Sugar intake increased markedly during this period
      due to its introduction in liquors, tea, coffee and desserts. We suggest that the
      introduction of sugar explains why gout was originally a disease of the wealthy
      and educated, but gradually became common throughout society.

PMID- 23175572
TI  - Use of Microfocused X-ray Techniques to Investigate the Mobilization of As by
      Oxalic Acid.
AB  - Improved linkages between aqueous phase transport and solid-phase reactions are
      needed to better predict and model transport of contaminants through the
      subsurface. Here we develop and apply a new method for measuring As mobilization
      in situ within soil columns that utilizes synchrotron-based X-ray fluorescence.
      By performing these measurements in situ during column transport experiments, we
      simultaneously monitor grain-scale solid phase reactions and column-scale
      transport. Arsenic may be effectively mobilized by oxalic acid but the
      geochemical and mineralogical factors that influence the rate and extent of
      mobilization are not well understood. Column experiments (~4 cm long * 0.635 cm
      ID) using As contaminated sediments from the Vineland Chemical Company Superfund
      site were performed on the laboratory bench as well as in the synchrotron
      beamline. Microfocused synchrotron X-ray fluorescence (MUSXRF) maps for As and Fe
      were collected at the same location in the columns (<1 mm(2)) before and during
      treatment with 10 mM oxalic acid. The fraction of As and Fe removed by oxalic
      acid treatment was calculated from the change in flux-normalized counts for each
      pixel in the map images, and these data were used to calculate kinetic parameters
      over the studied area. Between 79% and 83% of the As was removed from the
      sediments by the oxalic acid treatment based on MUSXRF data; these removal
      percentages agreed well with laboratory data based on column effluent (88-95%).
      Considerably less Fe was removed by oxalic acid treatment, 14-25% based on MUSXRF
      counts, which is somewhat higher than the 7-9% calculated from laboratory column
      effluent concentrations. Microfocused X-ray absorption near edge spectroscopy
      (MUXANES) on a subset of points indicates most of the Fe was oxidized and present
      as a mixture of goethite, hematite, and ferrihydrite on sand grain coatings.
      Treatment with oxalic acid led to subtle shifts in Fe (III) species following
      oxalic acid treatment, either removing ferrihydrite or transforming it to more
      stable oxides; however, Fe redox states were not impacted. Kinetics information
      extracted from MUSXRF data compared favorably with rates of As removal from
      observed As breakthrough curves. The average pseudo-first order As removal rate
      constant was calculated to be 0.015 min(-1) +/- 0.002 (+/- average standard
      error, N=400) based on changes in MUSXRF counts over time. The spatial variation
      observed in the rate constant is likely a result of differences in the mineral
      substrate or As retention mechanism. Geochemical models created using the
      calculated As removal rate constants showed agreement with As breakthrough curves
      for both a small column (4.25 cm * 0.635 cm ID) and a larger column (23.5 cm *
      4.2 cm ID), indicating that the processes studied using the microprobe are
      representative and often can be predictive of larger systems. While this work was
      used to understand the processes that regulate As release and transport, the
      methods developed here could be used to study a wide variety of reaction
      processes, including contaminant removal due to chemical treatment, mineral
      precipitation due to changing redox characteristics, and solid phase
      transformations.

PMID- 23175573
TI  - Pediatric regional anesthesia: drawing inferences on safety from prospective
      registries and case reports.

PMID- 23175574
TI  - We can't go home again: advances in the resuscitation of patients with
      polytrauma.

PMID- 23175575
TI  - Anesthesia & analgesia by the numbers: then & now.

PMID- 23175576
TI  - Seeing is believing: ultrasound-guided internal jugular vein cannulation.

PMID- 23175577
TI  - Bohr dead space calculation.

PMID- 23175578
TI  - Cuff perforation by dislocated electrodes of an clectromyogram tube.

PMID- 23175582
TI  - Statistical measures for workload capacity analysis.
AB  - A critical component of how we understand a mental process is given by measuring
      the effect of varying the workload. The capacity coefficient (Townsend & Nozawa,
      1995; Townsend & Wenger, 2004) is a measure on response times for quantifying
      changes in performance due to workload. Despite its precise mathematical
      foundation, until now rigorous statistical tests have been lacking. In this
      paper, we demonstrate statistical properties of the components of the capacity
      measure and propose a significance test for comparing the capacity coefficient to
      a baseline measure or two capacity coefficients to each other.

PMID- 23175583
TI  - 5'-Terminal chemical capping of spliced leader RNAs.
AB  - Spliced leader (SL) RNA trans-splicing adds a 2,2,7-trimethylguanosine cap (TMG)
      and a 22-nucleotide sequence, the SL, to the 5' end of mRNAs. Both non-trans
      spliced with a monomethylguanosine cap (MMG) and trans-spliced mRNAs co-exist in
      trans-splicing metazoan cells. Efficient translation of TMG-capped mRNAs in
      nematodes requires a defined core of nucleotides within the SL sequence. Here we
      present a chemical procedure for the preparation and purification of 5'-terminal
      capped MMG and TMG wild-type, and mutant 22 nt spliced leader RNAs
      (GGU/ACUUAAUUACCCAAGUUUGAG) with or without a 3' biotin tag.

PMID- 23175584
TI  - Microwave-assisted Hantzsch thiazole synthesis of N-phenyl-4-(6-phenylimidazo[2,1
      b]thiazol-5-yl)thiazol-2-amines from the reaction of 2-chloro-1-(6
      phenylimidazo[2,1-b]thiazol-5-yl)ethanones and thioureas.
AB  - N-Phenyl-4-(6-phenylimidazo[2,1-b]thiazol-5-yl)thiazol-2-amines (6a-q) have been
      synthesized by the Hantzsch thiazole reaction of 2-chloro-1-(6-phenylimidazo[2,1
      b]thiazol-5-yl)ethanones (4a-e) with suitably substituted thioureas using
      microwave heating. The ethanones (4a-e) were prepared by the reaction of 6
      phenylimidazo[2,1-b]thiazoles (3a-e) with chloroacetylchloride in refluxing 1,4
      dioxane whereas the thiazoles (3a-e) were synthesized by the reaction of 2-bromo
      1-phenylethanones (2a-e) with thiazol-2-amine in refluxing acetone.

PMID- 23175585
TI  - N-Myristoylglutamic Acid Derivative of 3'-Fluoro-3'-Deoxythymidine as an
      Organogel.
AB  - Designing microbicidal gels of anti-HIV drugs for local application to prevent
      HIV infection is a subject of major interest. 3'-Fluoro-3'-deoxythymidine (FLT),
      a nucleoside reverse transcriptase inhibitor (NRTI), was conjugated with a N
      myristoyl glutamate scaffold. The conjugate showed gelation at 1% (w/w) in
      different organic solvents, such as toluene, dichloromethane, and chloroform. The
      gels were opaque and stable at room temperature. The results indicate that
      myristoyl glutamate derivative of FLT can form an organogel. The gel could have
      potential application as a topical anti-HIV microbicidal agent.

PMID- 23175586
TI  - Enzymatic synthesis of N-Acylethanolamines: Direct method for the aminolysis of
      esters.
AB  - Immobilized Candida antarctica (Novozyme 435) catalyzed synthesis of N
      acylethanolamines is described. Treatment of methyl esters with lipase and amines
      yielded the desired amides within 2-24 hrs with yields ranging from 41-98%.

PMID- 23175587
TI  - Sources of variation in flow cytometric analysis of aquatic species sperm: The
      effect of cryoprotectants on flow cytometry scatter plots and subsequent
      population gating.
AB  - The use of fluorescent staining and flow cytometry to assess sperm quality in
      aquatic species has increased over the past decade, but comparisons among studies
      are difficult or impossible due to variation in application, analysis, and
      reporting of protocols and data.The goal of the present study was to determine
      the effect of exposure to two cryoprotectants commonly used for cryopreservation
      of sperm from aquatic species on the accuracy of flow cytometric assessment of
      sperm quality.Membrane integrity of zebrafish (Danio rerio) sperm exposed to 10%
      and 20%methanol and dimethyl sulfoxide (DMSO)in 300 mOsm kg(-1) Hanks' balanced
      salt solution (HBSS) or calcium-free HBSSwas determined using SYBR 14/propidium
      iodide staining. Both cryoprotectants significantly affected forward-scatter and
      side-scatter characteristics of sperm samples, resulting in significant changes
      in the number of total and gated events, and in the number and percentage of
      intact cells. These results indicate that it cannot be assumed that the approach
      to flow cytometric analysis of fresh sperm will be applicable to cryoprotectant
      treated or cryopreserved sperm. In total, we document examples of five
      potentially interacting factors that produce errors of 5 to 50% each, resulting
      in underestimates and overestimates of total and intact sperm (actual numbers and
      percentages) in the presence of the two most commonly used cryoprotectants at the
      concentrations used most often for cryopreservation of sperm from aquatic
      species. This study provides methods to reduce or eliminate these errors and
      recommendations necessary for standardization and reporting.

PMID- 23175588
TI  - A fully implicit finite element method for bidomain models of cardiac
      electromechanics.
AB  - We propose a novel, monolithic, and unconditionally stable finite element
      algorithm for the bidomain-based approach to cardiac electromechanics. We
      introduce the transmembrane potential, the extracellular potential, and the
      displacement field as independent variables, and extend the common two-field
      bidomain formulation of electrophysiology to a three-field formulation of
      electromechanics. The intrinsic coupling arises from both excitation-induced
      contraction of cardiac cells and the deformation-induced generation of intra
      cellular currents. The coupled reaction-diffusion equations of the electrical
      problem and the momentum balance of the mechanical problem are recast into their
      weak forms through a conventional isoparametric Galerkin approach. As a novel
      aspect, we propose a monolithic approach to solve the governing equations of
      excitation-contraction coupling in a fully coupled, implicit sense. We
      demonstrate the consistent linearization of the resulting set of non-linear
      residual equations. To assess the algorithmic performance, we illustrate
      characteristic features by means of representative three-dimensional initial
      boundary value problems. The proposed algorithm may open new avenues to patient
      specific therapy design by circumventing stability and convergence issues
      inherent to conventional staggered solution schemes.

PMID- 23175590
TI  - Wireless sensors and sensor networks for homeland security applications.
AB  - New sensor technologies for homeland security applications must meet the key
      requirements of sensitivity to detect agents below risk levels, selectivity to
      provide minimal false-alarm rates, and response speed to operate in high
      throughput environments, such as airports, sea ports, and other public places.
      Chemical detection using existing sensor systems is facing a major challenge of
      selectivity. In this review, we provide a brief summary of chemical threats of
      homeland security importance; focus in detail on modern concepts in chemical
      sensing; examine the origins of the most significant unmet needs in existing
      chemical sensors; and, analyze opportunities, specific requirements, and
      challenges for wireless chemical sensors and wireless sensor networks (WSNs). We
      further review a new approach for selective chemical sensing that involves the
      combination of a sensing material that has different response mechanisms to
      different species of interest, with a transducer that has a multi-variable signal
      transduction ability. This new selective chemical-sensing approach was realized
      using an attractive ubiquitous platform of battery-free passive radio-frequency
      identification (RFID) tags adapted for chemical sensing. We illustrate the
      performance of RFID sensors developed in measurements of toxic industrial
      materials, humidity-independent detection of toxic vapors, and detection of
      chemical-agent simulants, explosives, and strong oxidizers.

PMID- 23175589
TI  - Position-dependent splicing activation and repression by SR and hnRNP proteins
      rely on common mechanisms.
AB  - Alternative splicing is regulated by splicing factors that modulate splice site
      selection. In some cases, however, splicing factors show antagonistic activities
      by either activating or repressing splicing. Here, we show that these opposing
      outcomes are based on their binding location relative to regulated 5' splice
      sites. SR proteins enhance splicing only when they are recruited to the exon.
      However, they interfere with splicing by simply relocating them to the opposite
      intronic side of the splice site. hnRNP splicing factors display analogous
      opposing activities, but in a reversed position dependence. Activation by SR or
      hnRNP proteins increases splice site recognition at the earliest steps of exon
      definition, whereas splicing repression promotes the assembly of nonproductive
      complexes that arrest spliceosome assembly prior to splice site pairing. Thus, SR
      and hnRNP splicing factors exploit similar mechanisms to positively or negatively
      influence splice site selection.

PMID- 23175591
TI  - Evolution of genome size in Carex (Cyperaceae) in relation to chromosome number
      and genomic base composition.
AB  - BACKGROUND AND AIMS: The genus Carex exhibits karyological peculiarities related
      to holocentrism, specifically extremely broad and almost continual variation in
      chromosome number. However, the effect of these peculiarities on the evolution of
      the genome (genome size, base composition) remains unknown. While in
      monocentrics, determining the arithmetic relationship between the chromosome
      numbers of related species is usually sufficient for the detection of particular
      modes of karyotype evolution (i.e. polyploidy and dysploidy), in holocentrics
      where chromosomal fission and fusion occur such detection requires knowledge of
      the DNA content. METHODS: The genome size and GC content were estimated in 157
      taxa using flow cytometry. The exact chromosome numbers were known for 96
      measured samples and were taken from the available literature for other taxa. All
      relationships were tested in a phylogenetic framework using the ITS tree of 105
      species. KEY RESULTS: The 1C genome size varied between 0.24 and 1.64 pg in Carex
      secalina and C. cuspidata, respectively. The genomic GC content varied from 34.8
      % to 40.6 % from C. secalina to C. firma. Both genomic parameters were positively
      correlated. Seven polyploid and two potentially polyploid taxa were detected in
      the core Carex clade. A strong negative correlation between genome size and
      chromosome number was documented in non-polyploid taxa. Non-polyploid taxa of the
      core Carex clade exhibited a higher rate of genome-size evolution compared with
      the Vignea clade. Three dioecious taxa exhibited larger genomes, larger
      chromosomes, and a higher GC content than their hermaphrodite relatives.
      CONCLUSIONS: Genomes of Carex are relatively small and very GC-poor compared with
      other angiosperms. We conclude that the evolution of genome and karyotype in
      Carex is promoted by frequent chromosomal fissions/fusions, rare polyploidy and
      common repetitive DNA proliferation/removal.

PMID- 23175592
TI  - Generating Functions for Multi-labeled Trees.
AB  - Multi-labeled trees are a generalization of phylogenetic trees that are used, for
      example, in the study of gene versus species evolution and as the basis for
      phylogenetic network construction. Unlike phylogenetic trees, in a leaf-multi
      labeled tree it is possible to label more than one leaf by the same element of
      the underlying label set. In this paper we derive formulae for generating
      functions of leaf-multi-labeled trees and use these to derive recursions for
      counting such trees. In particular, we prove results which generalize previous
      theorems by Harding on so-called tree-shapes, and by Otter on relating the number
      of rooted and unrooted phylogenetic trees.

PMID- 23175593
TI  - Integration of Metallic Nanostructures in Fluidic Channels for Fluorescence and
      Raman Enhancement by Nanoimprint Lithography and Lift-off on Compositional Resist
      Stack.
AB  - We present and demonstrate a novel fabrication method to integrate metallic
      nanostructures into fluidic systems, using nanoimprint lithography and lift-off
      on a compositional resist stack, which consists of multi-layers of SiO(2) and
      polymer patterned from different fabrication steps. The lift-off of the stack
      allows the final nano-features precisely aligned in the proper locations inside
      fluidic channels. The method provides high-throughput low-cost patterning and
      compatibility with various fluidic channel designs, and will be useful for
      fluorescence and Raman scattering enhancement in nano-fluidic systems.

PMID- 23175594
TI  - Concentration-resistance relationships with Pseudomonas aeruginosa exposed to
      doripenem and ciprofloxacin in an in vitro model.
AB  - OBJECTIVES: To compare the abilities of doripenem and ciprofloxacin to restrict
      the enrichment of resistant Pseudomonas aeruginosa, multiple antibiotic dosing
      regimens were simulated in an in vitro model at comparable ratios of the 24 h AUC
      (AUC24) to the MIC. METHODS: Three clinical isolates of ciprofloxacin-resistant
      P. aeruginosa (MIC of doripenem 1 mg/L, MIC of ciprofloxacin 4 mg/L) were exposed
      to thrice-daily doripenem or twice-daily ciprofloxacin for 3 days at AUC24/MIC
      ratios from 50 to 170 h (doripenem) and from 55 to 180 h (ciprofloxacin).
      RESULTS: Doripenem- and ciprofloxacin-resistant mutants were enriched at
      antibiotic concentrations that fell into the mutant selection window for >= 45%
      and >= 60% of the dosing interval, respectively. The anti-mutant effects of
      doripenem and ciprofloxacin expressed by the area under the bacterial mutant
      concentration-time curve (AUBCM) depended on the AUC24/MIC ratio, and the AUBCM
      log AUC24/MIC relationships were antibiotic specific. CONCLUSION: Based on
      AUC24/MIC relationships with AUBCM, a greater anti-mutant potential was predicted
      for doripenem compared with ciprofloxacin.

PMID- 23175595
TI  - Influence of caregiver network support and caregiver psychopathology on child
      mental health need and service use in the LONGSCAN study.
AB  - Using structural equation modeling, this study examined the relationship of
      caregiver network support on caregiver and child mental health need, as well as
      child mental health service use among 1075 8-year-old children participating in
      the LONGSCAN study. The final model showed acceptable fit (chi(2) = 301.476, df =
      136, p<0.001; RMSEA = 0.052; CFI = 0.95). Caregiver and child mental health needs
      were positively related. As predicted, caregiver network support exerted a
      protective effect, with greater levels of caregiver network support predictive of
      lower caregiver and child need. Contrary to prediction, however, caregiver
      network support was not directly related to child service use. Higher child need
      was directly related to child service use, especially among children whose
      caregivers had mental health problems. The findings appear to indicate that lower
      levels of caregiver network support may exert its impact on child service use
      indirectly by increasing caregiver and child need, rather than by directly
      increasing the likelihood of receiving services, especially for African American
      children.

PMID- 23175596
TI  - Adult Recollections of Peer Victimization during Middle School: Forms and
      Consequences.
AB  - This study examined memories of peer victimization by eliciting narratives from
      university students (N = 210) about one previous experience of peer maltreatment
      during middle school, and investigating how these recollections related to
      current levels of adjustment. The majority of participants described an
      experience of social victimization (70.0%) or physical victimization (16.7%), and
      analyses examining form of victimization were limited to these participants (n =
      182). Previous experiences of peer maltreatment during middle school were
      associated with negative indices of adjustment in early adulthood. The
      implications of our findings for school intervention programs are discussed.

PMID- 23175597
TI  - Development of high-productivity, strong cation-exchange adsorbers for protein
      capture by graft polymerization from membranes with different pore sizes.
AB  - This paper describes the surface modification of macroporous membranes using ATRP
      (atom transfer radical polymerization) to create cation-exchange adsorbers with
      high protein binding capacity at high product throughput. The work is motivated
      by the need for a more economical and rapid capture step in downstream processing
      of protein therapeutics. Membranes with three reported nominal pore sizes (0.2,
      0.45, 1.0 MUm) were modified with poly(3-sulfopropyl methacrylate, potassium
      salt) tentacles, to create a high density of protein binding sites. A special
      formulation was used in which the monomer was protected by a crown ether to
      enable surface-initiated ATRP of this cationic polyelectrolyte. Success with
      modification was supported by chemical analysis using Fourier-transform infrared
      spectroscopy and indirectly by measurement of pure water flux as a function of
      polymerization time. Uniformity of modification within the membranes was
      visualized with confocal laser scanning microscopy. Static and dynamic binding
      capacities were measured using lysozyme protein to allow comparisons with
      reported performance data for commercial cation-exchange materials. Dynamic
      binding capacities were measured for flow rates ranging from 13 to 109 column
      volumes (CV)/min. Results show that this unique ATRP formulation can be used to
      fabricate cation-exchange membrane adsorbers with dynamic binding capacities as
      high as 70 mg/mL at a throughput of 100 CV/min and unprecedented productivity of
      300 mg/mL/min.

PMID- 23175598
TI  - The Individualized Classroom Assessment Scoring System (inCLASS): Preliminary
      Reliability and Validity of a System for Observing Preschoolers' Competence in
      Classroom Interactions.
AB  - This paper introduces the Individualized Classroom Assessment Scoring System
      (inCLASS), an observation tool that targets children's interactions in preschool
      classrooms with teachers, peers, and tasks. In particular, initial evidence is
      reported of the extent to which the inCLASS meets the following psychometric
      criteria: inter-rater reliability, normal distributions and adequate range,
      construct validity, and criterion-related validity. These initial findings
      suggest that the inCLASS has the potential to provide an authentic,
      contextualized assessment of young children's classroom behaviors. Future
      directions for research with the inCLASS are discussed.

PMID- 23175599
TI  - Micro-patterning and characterization of PHEMA-co-PAM-based optical chemical
      sensors for lab-on-a-chip applications.
AB  - We report a novel method for wafer level, high throughput optical chemical sensor
      patterning, with precise control of the sensor volume and capability of producing
      arbitrary microscale patterns. Monomeric oxygen (O(2)) and pH optical probes were
      polymerized with 2-hydroxyethyl methacrylate (HEMA) and acrylamide (AM) to form
      spin-coatable and further crosslinkable polymers. A micro-patterning method based
      on micro-fabrication techniques (photolithography, wet chemical process and
      reactive ion etch) was developed to miniaturize the sensor film onto glass
      substrates in arbitrary sizes and shapes. The sensitivity of fabricated micro
      patterns was characterized under various oxygen concentrations and pH values. The
      process for spatially integration of two sensors (Oxygen and pH) on the same
      substrate surface was also developed, and preliminary fabrication and
      characterization results were presented. To the best of our knowledge, it is the
      first time that poly (2-hydroxylethyl methacrylate)-co-poly (acrylamide) (PHEMA
      co-PAM)-based sensors had been patterned and integrated at the wafer level with
      micron scale precision control using microfabrication techniques. The developed
      methods can provide a feasible way to miniaturize and integrate the optical
      chemical sensor system and can be applied to any lab-on-a-chip system, especially
      the biological micro-systems requiring optical sensing of single or multiple
      analytes.

PMID- 23175600
TI  - Real-time Recognition of Mycobacterium tuberculosis and Lipoarabinomannan using
      the Quartz Crystal Microbalance.
AB  - A quartz crystal microbalance (QCM) immunosensor has been successfully employed
      to screen for both whole Mycobacteria tuberculosis (Mtb) bacilli and a Mtb
      surface antigen, lipoarabinomannan (LAM). One of the most abundant components of
      the Mtb cell surface, LAM, may be detected without the presence of the entire
      bacterium. Using available antibodies with proven utility in enzyme-linked
      immunoassays (ELISAs), a sensor was designed to measure Mtb bacilli and LAM.
      Equilibrium association constants (K(a)) were determined for the interaction of
      Mtb with immobilized alpha-LAM and anti-H37Rv antibodies, where avidity was seen
      to strengthen this interaction and provide for greater binding than might have
      otherwise been achieved. The binding of LAM to immobilized alpha-LAM had a high
      associate rate constant (k(a)) allowing for rapid detection. Evaluating these
      binding constants helped the compare the sensitivity of these immunosensors to
      conventional ELISAs. The use of these assays with the better antibodies may allow
      for immunosensor use in determining LAM as a point-of-care (POC) diagnostic for
      Mtb.

PMID- 23175601
TI  - Direct comparison of the generalized Visual Analog Scale (gVAS) and general
      Labeled Magnitude Scale (gLMS).
AB  - Hundreds of studies have used the generalized Labeled Magnitude Scale (gLMS) to
      collect intensity data. Recent work on generalized affective scales like the
      Labeled Affective Magnitude (LAM) scale and Labeled Hedonic Scale (LHS) suggest a
      substantial proportion of participants fail to use the entire range of
      generalized scales, marking only at the adjective labels. This categorical
      behavior (i.e., clustering) is not limited to affective ratings, as it is well
      known anecdotally among users of the gLMS. One way to stop this behavior would be
      to retain a generalized top anchor and cross modal orientation procedure while
      stripping away the internal adjectives. Several published studies have already
      used this variant, the generalized Visual Analog Scale (gVAS). Because there are
      no reports directly comparing the gVAS and gLMS head to head, we did so in two
      experiments. In Experiment 1, participants (n=87) were randomized to 1 of 3
      conditions to test effects of scaling instructions and scale structure. In
      Experiment 2, participants (n=58) assessed perceived ease of use and resolving
      power for each scale in a two-session crossover design. gLMS data showed evidence
      of categorical behavior, while gVAS data did not. Explicitly instructing
      participants to rate between adjectives did not reduce this behavior. The gLMS
      was easier to use according to participants, but resulted in non-normal data due
      to clustering near the adjective labels. gVAS data did not show categorical
      behavior, as there are no adjectives to cluster around, but the gVAS sacrifices
      semantic information about the magnitude of response. Regardless of scale type,
      participants felt the cross-modal orientation procedure helped them understand
      how to use the scale. Both scales were able to discriminate between sucrose
      samples in a concentration series. Relative tradeoffs between the two methods
      suggest the choice of one scale over the other depends on the specific goals and
      context of the project.

PMID- 23175602
TI  - A complex network framework for unbiased statistical analyses of DNA-DNA contact
      maps.
AB  - Experimental techniques for the investigation of three-dimensional (3D) genome
      organization are being developed at a fast pace. Currently, the associated
      computational methods are mostly specific to the individual experimental
      approach. Here we present a general statistical framework that is widely
      applicable to the analysis of genomic contact maps, irrespective of the data
      acquisition and normalization processes. Within this framework DNA-DNA contact
      data are represented as a complex network, for which a broad number of directly
      applicable methods already exist. In such a network representation, DNA segments
      and contacts between them are denoted as nodes and edges, respectively.
      Furthermore, we present a robust method for generating randomized contact
      networks that explicitly take into account the inherent 3D nature of the genome
      and serve as realistic null-models for unbiased statistical analyses. By
      integrating a variety of large-scale genome-wide datasets we demonstrate that
      meiotic crossover sites display enriched genomic contacts and that cohesin-bound
      genes are significantly colocalized in the yeast nucleus. We anticipate that the
      complex network framework in conjunction with the randomization of DNA-DNA
      contact networks will become a widely used tool in the study of nuclear
      architecture.

PMID- 23175603
TI  - HOCOMOCO: a comprehensive collection of human transcription factor binding sites
      models.
AB  - Transcription factor (TF) binding site (TFBS) models are crucial for
      computational reconstruction of transcription regulatory networks. In existing
      repositories, a TF often has several models (also called binding profiles or
      motifs), obtained from different experimental data. Having a single TFBS model
      for a TF is more pragmatic for practical applications. We show that integration
      of TFBS data from various types of experiments into a single model typically
      results in the improved model quality probably due to partial correction of
      source specific technique bias. We present the Homo sapiens comprehensive model
      collection (HOCOMOCO, http://autosome.ru/HOCOMOCO/,
      http://cbrc.kaust.edu.sa/hocomoco/) containing carefully hand-curated TFBS models
      constructed by integration of binding sequences obtained by both low- and high
      throughput methods. To construct position weight matrices to represent these TFBS
      models, we used ChIPMunk software in four computational modes, including newly
      developed periodic positional prior mode associated with DNA helix pitch. We
      selected only one TFBS model per TF, unless there was a clear experimental
      evidence for two rather distinct TFBS models. We assigned a quality rating to
      each model. HOCOMOCO contains 426 systematically curated TFBS models for 401
      human TFs, where 172 models are based on more than one data source.

PMID- 23175604
TI  - Las1 interacts with Grc3 polynucleotide kinase and is required for ribosome
      synthesis in Saccharomyces cerevisiae.
AB  - Ribosome biogenesis is a multi-step process that couples cell growth with cell
      proliferation. Although several large-scale analysis of pre-ribosomal particles
      have identified numerous trans-acting factors involved in this process, many
      proteins involved in pre-rRNA processing and ribosomal subunit maturation have
      yet to be identified. Las1 was originally identified in Saccharomyces cerevisiae
      as a protein involved in cell morphogenesis. We previously demonstrated that the
      human homolog, Las1L, is required for efficient ITS2 rRNA processing and
      synthesis of the 60S ribosomal subunit. Here, we report that the functions of
      Las1 in ribosome biogenesis are also conserved in S. cerevisiae. Depletion of
      Las1 led to the accumulation of both the 27S and 7S rRNA intermediates and
      impaired the synthesis of the 60S subunit. We show that Las1 co-precipitates
      mainly with the 27S rRNA and associates with an Nsa1 and Rix1-containing pre-60S
      particle. We further identify Grc3 as a major Las1-interacting protein. We
      demonstrate that the kinase activity of Grc3 is required for efficient pre-rRNA
      processing and that depletion of Grc3 leads to rRNA processing defects similar to
      the ones observed in Las1-depleted cells. We propose that Las1 and Grc3 function
      together in a conserved mechanism to modulate rRNA processing and eukaryotic
      ribosome biogenesis.

PMID- 23175605
TI  - The EBI enzyme portal.
AB  - The availability of comprehensive information about enzymes plays an important
      role in answering questions relevant to interdisciplinary fields such as
      biochemistry, enzymology, biofuels, bioengineering and drug discovery. At the
      EMBL European Bioinformatics Institute, we have developed an enzyme portal
      (http://www.ebi.ac.uk/enzymeportal) to provide this wealth of information on
      enzymes from multiple in-house resources addressing particular data classes:
      protein sequence and structure, reactions, pathways and small molecules. The fact
      that these data reside in separate databases makes information discovery
      cumbersome. The main goal of the portal is to simplify this process for end
      users.

PMID- 23175606
TI  - WholeCellKB: model organism databases for comprehensive whole-cell models.
AB  - Whole-cell models promise to greatly facilitate the analysis of complex
      biological behaviors. Whole-cell model development requires comprehensive model
      organism databases. WholeCellKB (http://wholecellkb.stanford.edu) is an open
      source web-based software program for constructing model organism databases.
      WholeCellKB provides an extensive and fully customizable data model that fully
      describes individual species including the structure and function of each gene,
      protein, reaction and pathway. We used WholeCellKB to create WholeCellKB-MG, a
      comprehensive database of the Gram-positive bacterium Mycoplasma genitalium using
      over 900 sources. WholeCellKB-MG is extensively cross-referenced to existing
      resources including BioCyc, KEGG and UniProt. WholeCellKB-MG is freely accessible
      through a web-based user interface as well as through a RESTful web service.

PMID- 23175607
TI  - CyanoLyase: a database of phycobilin lyase sequences, motifs and functions.
AB  - CyanoLyase (http://cyanolyase.genouest.org/) is a manually curated sequence and
      motif database of phycobilin lyases and related proteins. These enzymes catalyze
      the covalent ligation of chromophores (phycobilins) to specific binding sites of
      phycobiliproteins (PBPs). The latter constitute the building bricks of
      phycobilisomes, the major light-harvesting systems of cyanobacteria and red
      algae. Phycobilin lyases sequences are poorly annotated in public databases.
      Sequences included in CyanoLyase were retrieved from all available genomes of
      these organisms and a few others by similarity searches using biochemically
      characterized enzyme sequences and then classified into 3 clans and 32 families.
      Amino acid motifs were computed for each family using Protomata learner.
      CyanoLyase also includes BLAST and a novel pattern matching tool (Protomatch)
      that allow users to rapidly retrieve and annotate lyases from any new genome. In
      addition, it provides phylogenetic analyses of all phycobilin lyases families,
      describes their function, their presence/absence in all genomes of the database
      (phyletic profiles) and predicts the chromophorylation of PBPs in each strain.
      The site also includes a thorough bibliography about phycobilin lyases and
      genomes included in the database. This resource should be useful to scientists
      and companies interested in natural or artificial PBPs, which have a number of
      biotechnological applications, notably as fluorescent markers.

PMID- 23175608
TI  - Phosphoinositide 3-kinase beta controls replication factor C assembly and
      function.
AB  - Genomic integrity is preserved by the action of protein complexes that control
      DNA homeostasis. These include the sliding clamps, trimeric protein rings that
      are arranged around DNA by clamp loaders. Replication factor C (RFC) is the clamp
      loader for proliferating cell nuclear antigen, which acts on DNA replication.
      Other processes that require mobile contact of proteins with DNA use alternative
      RFC complexes that exchange RFC1 for CTF18 or RAD17. Phosphoinositide 3-kinases
      (PI3K) are lipid kinases that generate 3-poly-phosphorylated-phosphoinositides at
      the plasma membrane following receptor stimulation. The two ubiquitous isoforms,
      PI3Kalpha and PI3Kbeta, have been extensively studied due to their involvement in
      cancer and nuclear PI3Kbeta has been found to regulate DNA replication and
      repair, processes controlled by molecular clamps. We studied here whether
      PI3Kbeta directly controls the process of molecular clamps loading. We show that
      PI3Kbeta associated with RFC1 and RFC1-like subunits. Only when in complex with
      PI3Kbeta, RFC1 bound to Ran GTPase and localized to the nucleus, suggesting that
      PI3Kbeta regulates RFC1 nuclear import. PI3Kbeta controlled not only RFC1- and
      RFC-RAD17 complexes, but also RFC-CTF18, in turn affecting CTF18-mediated
      chromatid cohesion. PI3Kbeta thus has a general function in genomic stability by
      controlling the localization and function of RFC complexes.

PMID- 23175609
TI  - Ion-dependent conformational switching by a DNA aptamer that induces
      remyelination in a mouse model of multiple sclerosis.
AB  - We recently reported that a guanosine-rich 40-mer DNA aptamer (LJM-3064) mediates
      remyelination in the Theiler's murine encephalomyelitis virus mouse model of
      multiple sclerosis. Here, we characterize the G-quadruplex forms of this aptamer
      in vitro, and demonstrate using circular dichroism spectroscopy that LJM-3064
      undergoes a monovalent ion-dependent conformational switch. In the presence of
      sodium ions and no potassium ions, LJM-3064 adopts an antiparallel-stranded G
      quadruplex structure. When presented with low concentrations of potassium ions in
      a buffer that mimics the composition of interstitial fluid and blood plasma, LJM
      3064 rapidly switches to a parallel-stranded G-quadruplex conformation, which is
      presumably the physiologically active folded form. We characterize these
      conformational states using dimethyl sulfate reactivity studies and Bal 31
      nuclease probing. Our analysis indicates that only the 5'-terminal 26 nucleotides
      are involved in G-quadruplex formation. Thermodynamic characterization of LJM
      3064 at physiologically relevant ion concentrations reveals the G-quadruplex to
      be metastable at human body temperature. These data provide important structural
      and thermodynamic insights that may be valuable in optimizing LJM-3064 as a
      therapeutic remyelinating agent.

PMID- 23175610
TI  - The mouse genome database: genotypes, phenotypes, and models of human disease.
AB  - The laboratory mouse is the premier animal model for studying human biology
      because all life stages can be accessed experimentally, a completely sequenced
      reference genome is publicly available and there exists a myriad of genomic tools
      for comparative and experimental research. In the current era of genome scale,
      data-driven biomedical research, the integration of genetic, genomic and
      biological data are essential for realizing the full potential of the mouse as an
      experimental model. The Mouse Genome Database (MGD;
      http://www.informatics.jax.org), the community model organism database for the
      laboratory mouse, is designed to facilitate the use of the laboratory mouse as a
      model system for understanding human biology and disease. To achieve this goal,
      MGD integrates genetic and genomic data related to the functional and phenotypic
      characterization of mouse genes and alleles and serves as a comprehensive catalog
      for mouse models of human disease. Recent enhancements to MGD include the
      addition of human ortholog details to mouse Gene Detail pages, the inclusion of
      microRNA knockouts to MGD's catalog of alleles and phenotypes, the addition of
      video clips to phenotype images, providing access to genotype and phenotype data
      associated with quantitative trait loci (QTL) and improvements to the layout and
      display of Gene Ontology annotations.

PMID- 23175611
TI  - Structure, phosphorylation and U2AF65 binding of the N-terminal domain of
      splicing factor 1 during 3'-splice site recognition.
AB  - Recognition of the 3'-splice site is a key step in pre-mRNA splicing and
      accomplished by a dynamic complex comprising splicing factor 1 (SF1) and the U2
      snRNP auxiliary factor 65-kDa subunit (U2AF65). Both proteins mediate protein
      protein and protein-RNA interactions for cooperative RNA-binding during
      spliceosome assembly. Here, we report the solution structure of a novel helix
      hairpin domain in the N-terminal region of SF1 (SF1(NTD)). The nuclear magnetic
      resonance- and small-angle X-ray scattering-derived structure of a complex of the
      SF1(NTD) with the C-terminal U2AF homology motif domain of U2AF65 (U2AF65(UHM))
      reveals that, in addition to the known U2AF65(UHM)-SF1 interaction, the helix
      hairpin domain forms a secondary, hydrophobic interface with U2AF65(UHM), which
      locks the orientation of the two subunits. Mutational analysis shows that the
      helix hairpin is essential for cooperative formation of the ternary SF1-U2AF65
      RNA complex. We further show that tandem serine phosphorylation of a conserved
      Ser80-Pro81-Ser82-Pro83 motif rigidifies a long unstructured linker in the SF1
      helix hairpin. Phosphorylation does not significantly alter the overall
      conformations of SF1, SF1-U2AF65 or the SF1-U2AF65-RNA complexes, but slightly
      enhances RNA binding. Our results indicate that the helix-hairpin domain of SF1
      is required for cooperative 3'-splice site recognition presumably by stabilizing
      a unique quaternary arrangement of the SF1-U2AF65-RNA complex.

PMID- 23175612
TI  - Physical and functional interaction between yeast Pif1 helicase and Rim1 single
      stranded DNA binding protein.
AB  - Pif1 helicase plays various roles in the maintenance of nuclear and mitochondrial
      genome integrity in most eukaryotes. Here, we used a proteomics approach called
      isotopic differentiation of interactions as random or targeted to identify
      specific protein complexes of Saccharomyces cerevisiae Pif1. We identified a
      stable association between Pif1 and a mitochondrial SSB, Rim1. In vitro co
      precipitation experiments using recombinant proteins indicated a direct
      interaction between Pif1 and Rim1. Fluorescently labeled Rim1 was titrated with
      Pif1 resulting in an increase in anisotropy and a K(d) value of 0.69 uM. Deletion
      mutagenesis revealed that the OB-fold domain and the C-terminal tail of Rim1 are
      both involved in interaction with Pif1. However, a Rim1 C-terminal truncation
      (Rim1DeltaC18) exhibited a nearly 4-fold higher K(d) value. Rim1 stimulated Pif1
      DNA helicase activity by 4- to 5-fold, whereas Rim1DeltaC18 stimulated Pif1 by 2
      fold. Hence, two regions of Rim1, the OB-fold domain and the C-terminal domain,
      interact with Pif1. One of these interactions occurs through the N-terminal
      domain of Pif1 because a deletion mutant of Pif1 (Pif1DeltaN) retained
      interaction with Rim1 but did not exhibit stimulation of helicase activity. In
      light of our in vivo and in vitro data, and previous work, it is likely that the
      Rim1-Pif1 interaction plays a role in coordination of their functions in mtDNA
      metabolism.

PMID- 23175613
TI  - BioGPS and MyGene.info: organizing online, gene-centric information.
AB  - Fast-evolving technologies have enabled researchers to easily generate data at
      genome scale, and using these technologies to compare biological states typically
      results in a list of candidate genes. Researchers are then faced with the
      daunting task of prioritizing these candidate genes for follow-up studies. There
      are hundreds, possibly even thousands, of web-based gene annotation resources
      available, but it quickly becomes impractical to manually access and review all
      of these sites for each gene in a candidate gene list. BioGPS (http://biogps.org)
      was created as a centralized gene portal for aggregating distributed gene
      annotation resources, emphasizing community extensibility and user
      customizability. BioGPS serves as a convenient tool for users to access known
      gene-centric resources, as well as a mechanism to discover new resources that
      were previously unknown to the user. This article describes updates to BioGPS
      made after its initial release in 2008. We summarize recent additions of features
      and data, as well as the robust user activity that underlies this community
      intelligence application. Finally, we describe MyGene.info (http://mygene.info)
      and related web services that provide programmatic access to BioGPS.

PMID- 23175614
TI  - LncRNADisease: a database for long-non-coding RNA-associated diseases.
AB  - In this article, we describe a long-non-coding RNA (lncRNA) and disease
      association database (LncRNADisease), which is publicly accessible at
      http://cmbi.bjmu.edu.cn/lncrnadisease. In recent years, a large number of lncRNAs
      have been identified and increasing evidence shows that lncRNAs play critical
      roles in various biological processes. Therefore, the dysfunctions of lncRNAs are
      associated with a wide range of diseases. It thus becomes important to understand
      lncRNAs' roles in diseases and to identify candidate lncRNAs for disease
      diagnosis, treatment and prognosis. For this purpose, a high-quality lncRNA
      disease association database would be extremely beneficial. Here, we describe the
      LncRNADisease database that collected and curated approximately 480 entries of
      experimentally supported lncRNA-disease associations, including 166 diseases.
      LncRNADisease also curated 478 entries of lncRNA interacting partners at various
      molecular levels, including protein, RNA, miRNA and DNA. Moreover, we annotated
      lncRNA-disease associations with genomic information, sequences, references and
      species. We normalized the disease name and the type of lncRNA dysfunction and
      provided a detailed description for each entry. Finally, we developed a
      bioinformatic method to predict novel lncRNA-disease associations and integrated
      the method and the predicted associated diseases of 1564 human lncRNAs into the
      database.

PMID- 23175616
TI  - High bandwidth piezoresistive force probes with integrated thermal actuation.
AB  - We present high-speed force probes with on-chip actuation and sensing for the
      measurement of pN-scale forces at the microsecond time scale. We achieve a high
      resonant frequency in water (1-100 kHz) with requisite low spring constants (0.3
      40 pN/nm) and low integrated force noise (1-100 pN) by targeting probe dimensions
      on the order of 300 nm thick, 1-2 MUm wide and 30-200 MUm long. Forces are
      measured using silicon piezoresistors while the probes are actuated thermally
      with an aluminum unimorph and silicon heater. The piezoresistive sensors are
      designed using open source numerical optimization code that incorporates
      constraints on operating temperature. Parylene passivation enables operation in
      ionic media and we demonstrate simultaneous actuation and sensing. The improved
      design and fabrication techniques that we describe enable a 10-20 fold
      improvement in force resolution or measurement bandwidth over prior
      piezoresistive cantilevers of comparable thickness.

PMID- 23175615
TI  - EuPathDB: the eukaryotic pathogen database.
AB  - EuPathDB (http://eupathdb.org) resources include 11 databases supporting
      eukaryotic pathogen genomic and functional genomic data, isolate data and
      phylogenomics. EuPathDB resources are built using the same infrastructure and
      provide a sophisticated search strategy system enabling complex interrogations of
      underlying data. Recent advances in EuPathDB resources include the design and
      implementation of a new data loading workflow, a new database supporting
      Piroplasmida (i.e. Babesia and Theileria), the addition of large amounts of new
      data and data types and the incorporation of new analysis tools. New data include
      genome sequences and annotation, strand-specific RNA-seq data, splice junction
      predictions (based on RNA-seq), phosphoproteomic data, high-throughput
      phenotyping data, single nucleotide polymorphism data based on high-throughput
      sequencing (HTS) and expression quantitative trait loci data. New analysis tools
      enable users to search for DNA motifs and define genes based on their genomic
      colocation, view results from searches graphically (i.e. genes mapped to
      chromosomes or isolates displayed on a map) and analyze data from columns in
      result tables (word cloud and histogram summaries of column content). The
      manuscript herein describes updates to EuPathDB since the previous report
      published in NAR in 2010.

PMID- 23175617
TI  - Positive Affect in the Midst of Distress: Implications for Role Functioning.
AB  - Stress has been shown to deplete the self-regulation resources hypothesized to
      facilitate effective role functioning. However, recent research suggests that
      positive affect may help to replenish these vital self-regulation resources.
      Based on revised Stress and Coping theory and the Broaden-and-Build theory of
      positive emotion, three studies provide evidence of the potential adaptive
      function of positive affect in the performance of roles for participants
      experiencing stress. Participants were students (Study 1), caregivers of ill
      children (Study 2), and individuals recently diagnosed with HIV (Study 3). In
      cross sectional analyses, using role functioning as an indicator of self
      regulation performance, we found that positive affect was significantly
      correlated with better self regulation performance, independent of the effects of
      negative affect. The effects were not as strong longitudinally, however, and
      there was little evidence of a reciprocal association between increases in
      positive affect and improvements in role functioning over time. The results
      provide some modest support for hypotheses stemming from the Broaden and Build
      model of positive emotion and revised Stress and Coping theory, both of which
      argue for unique adaptive functions of positive affect under stressful
      conditions.

PMID- 23175618
TI  - Impression Management in Survey Responding: Easier for Collectivists or
      Individualists?
AB  - Three experiments indicate that when individualists and collectivists engage in
      impression management on self-reports, they do so through different psychological
      mechanism s. Collectivists do so through a relatively automatic process. Thus,
      they can impression manage even when cognitively busy. Individualists impression
      manage through a more effortful process. Therefore, they can do so only when the
      situation permits effortful processing. These findings highlight distinct
      conditions under which social norms may influence consumer self-reports across
      cultures.

PMID- 23175619
TI  - An update on mindfulness meditation as a self-help treatment for anxiety and
      depression.
AB  - In recent years, complementary and alternative medicine (CAM) treatments have
      increased in popularity. This is especially true for treatments that are related
      to exercise and mindfulness-based interventions (MBIs) in the treatment of both
      mental and physical illness. MBIs, such as Mindfulness-based Cognitive Therapy
      (MBCT) and Mindfulness-Based Stress Reduction (MBSR), which are derived from
      ancient Buddhist and Yoga philosophies, have become popular treatments in
      contemporary psychotherapy. While there is growing evidence that supports the
      role of these interventions in relapse prevention, little is known about the role
      that MBIs play in the treatment of acute symptoms of depression and anxiety. Even
      less is known about the importance of specific components of MBIs (eg,
      mindfulness meditation [MM]) and the overall impact that these interventions have
      on the experience or expression of psychological distress. Moreover, few studies
      have rigorously evaluated the dose-response relationship that is required to
      effect positive symptom change and the mechanisms of change that are responsible
      for observed improvements. This review will define meditation and mindfulness,
      discuss the relationship between stress and health and how MM relates to
      therapeutically engaging the relaxation response, and review the empirical
      findings that are related to the efficacy of MM in the treatment of depression
      and anxiety symptoms. Given the paucity of research that examines the
      applications of these treatments in clinical populations, the limitations of
      applying these findings to clinical samples will be mentioned. A brief review of
      the issues related to the possible mechanisms of change and the dose-response
      relationship regarding MBIs, particularly MM, will be provided. Finally,
      limitations of the extant literature and future directions for further
      exploration of this topic will be offered.

PMID- 23175621
TI  - New primary renal diagnosis codes for the ERA-EDTA.
AB  - The European Renal Association-European Dialysis and Transplant Association (ERA
      EDTA) Registry has produced a new set of primary renal diagnosis (PRD) codes that
      are intended for use by affiliated registries. It is designed specifically for
      use in renal centres and registries but is aligned with international coding
      standards supported by the WHO (International Classification of Diseases) and the
      International Health Terminology Standards Development Organization (SNOMED
      Clinical Terms). It is available as supplementary material to this paper and free
      on the internet for non-commercial, clinical, quality improvement and research
      use, and by agreement with the ERA-EDTA Registry for use by commercial
      organizations. Conversion between the old and the new PRD codes is possible. The
      new codes are very flexible and will be actively managed to keep them up-to-date
      and to ensure that renal medicine can remain at the forefront of the electronic
      revolution in medicine, epidemiology research and the use of decision support
      systems to improve the care of patients.

PMID- 23175620
TI  - Challenges and Recent Progress in the Development of a Closed-loop Artificial
      Pancreas.
AB  - Pursuit of a closed-loop artificial pancreas that automatically controls the
      blood glucose of individuals with type 1 diabetes has intensified during the past
      six years. Here we discuss the recent progress and challenges in the major steps
      towards a closed-loop system. Continuous insulin infusion pumps have been widely
      available for over two decades, but "smart pump" technology has made the devices
      easier to use and more powerful. Continuous glucose monitoring (CGM) technology
      has improved and the devices are more widely available. A number of approaches
      are currently under study for fully closed-loop systems; most manipulate only
      insulin, while others manipulate insulin and glucagon. Algorithms include on-off
      (for prevention of overnight hypoglycemia), proportional-integral-derivative
      (PID), model predictive control (MPC) and fuzzy logic based learning control.
      Meals cause a major "disturbance" to blood glucose, and we discuss techniques
      that our group has developed to predict when a meal is likely to be consumed and
      its effect. We further examine both physiology and device-related challenges,
      including insulin infusion set failure and sensor signal attenuation. Finally, we
      discuss the next steps required to make a closed-loop artificial pancreas a
      commercial reality.

PMID- 23175622
TI  - Influence of imatinib interruption and rechallenge on the residual disease in
      patients with advanced GIST: results of the BFR14 prospective French Sarcoma
      Group randomised, phase III trial.
AB  - BACKGROUND: We previously demonstrated that interruption of imatinib mesylate
      (IM) in responding patients (pts) with advanced gastrointestinal stromal tumours
      (GISTs) results in rapid reprogression. The impact of interruption on residual
      tumour, quality of response and secondary resistance has not been fully
      investigated. PATIENTS AND METHODS: Within the BRF14 study, 71 non-progressing
      patients were randomly assigned in the interruption arms after 1, 3 or 5 years.
      IM was resumed in the case of progressive disease (PD). Tumour status at
      randomisation, relapse and after IM rechallenge, progression-free survival (PFS)
      and time to secondary resistance were analysed. RESULTS: At data cut-off, 51 of
      71 patients had restarted IM following documented PD. Eighteen patients (35%)
      progressed on known lesions only, while 33 patients (65%) had new lesions, with
      concomitant progression of known lesions in 17 patients. Only 8 (42%) of complete
      remission (CR) patients and 12 (52%) of partial response (PR) patients at
      randomisation achieved a new CR and PR. Patients progressing rapidly after
      interruption had a poorer prognosis. Tumour status at randomisation influenced
      time to progression after rechallenge. CONCLUSION: In advanced GIST patients
      interrupting IM, quality of response upon reintroduction did not reach the tumour
      status observed at randomisation. Rapid progression after imatinib interruption
      is associated with poor PFS after reintroduction.

PMID- 23175623
TI  - Shorter bevacizumab infusions do not increase the incidence of proteinuria and
      hypertension.
AB  - BACKGROUND: A previous study has shown that shorter bevacizumab infusions (0.5
      mg/kg/min) can be safely administered without increasing the risk of infusion
      related hypersensitivity reactions (HSRs). However, the risk of proteinuria and
      hypertension in patients receiving shorter infusions of bevacizumab is
      undetermined. PATIENTS AND METHODS: This was a multicenter, prospective,
      observational study in patients receiving <10 mg/kg of bevacizumab infused over
      0.5 mg/kg/min. Patients were observed until discontinuation of bevacizumab for
      progression of cancer or toxicity. The incidence of hypertension and proteinuria
      was compared with a prior cohort of patients who had received standard duration
      infusions of bevacizumab. RESULTS: Sixty-three patients received a total of 392
      doses of shorter bevacizumab infusions. Nineteen (30.2%) patients experienced
      proteinuria while receiving bevacizumab. Out of 19 patients, 13 had grade 1 and 6
      had grade 2 proteinuria. None of the patients experienced grade 3 or 4
      proteinuria. Hypertension was reported in 32 (50.8%) patients receiving
      bevacizumab. Twelve (19%) patients developed grade 3 or greater hypertension on
      bevacizumab. The incidence of proteinuria and hypertension was 38.3% and 56.6%,
      respectively, in patients (N = 120, 1347 infusions) receiving standard duration
      infusions of bevacizumab. CONCLUSIONS: Shorter bevacizumab infusions (0.5
      mg/kg/min) do not increase the risk of proteinuria and hypertension.

PMID- 23175625
TI  - Prevalence of depression in adults with cancer: a systematic review.
AB  - BACKGROUND: Depression has substantial effects on cancer patients' quality of
      life. Estimates of its prevalence vary widely. We aimed to systematically review
      published studies to obtain the best estimate of the prevalence of depression in
      clinically meaningful subgroups of cancer patients. DESIGN: Systematic review
      that addressed the limitations of previous reviews by (i) including only studies
      that used diagnostic interviews; (ii) including only studies that met basic
      quality criteria (random or consecutive sampling, >=70% response rate, clear
      definition of depression caseness, sample size >=100); (iii) grouping studies
      into clinically meaningful subgroups; (iv) describing the effect on prevalence
      estimates of different methods of diagnosing depression. RESULTS: Of 66 relevant
      studies, only 15 (23%) met quality criteria. The estimated prevalence of
      depression in the defined subgroups was as follows: 5% to 16% in outpatients, 4%
      to 14% in inpatients, 4% to 11% in mixed outpatient and inpatient samples and 7%
      to 49% in palliative care. Studies which used expert interviewers (psychiatrists
      or clinical psychologists) reported lower prevalence estimates. CONCLUSIONS: Of
      the large number of relevant studies, few met our inclusion criteria, and
      prevalence estimates are consequently imprecise. We propose that future studies
      should be designed to meet basic quality criteria and employ expert interviewers.

PMID- 23175626
TI  - ECD-like peptide fragmentation at atmospheric pressure.
AB  - Fragmentation of multiply-charged peptide ions via interaction with products of
      gas discharge at atmospheric pressure conditions was studied using ion mobility
      separation - fragmentation cell - linear ion trap mass spectrometer. The observed
      fragmentation spectra mainly consisted of c- type ions that are specific to
      electron capture dissociation. Experiments with different gases flowing through
      the discharge and different discharge polarities suggested that fragmentation
      proceeds via capture of free electrons. Fragmentation of a model phosphorylated
      peptide using this technique produced c- type fragments with an intact
      phosphorylation group. High field asymmetric waveform ion mobility separation of
      a peptide mixture prior to the fragmentation cell demonstrated the feasibility of
      conducting MS/MS-like experiments at atmospheric pressure conditions.

PMID- 23175624
TI  - ESMO Guidelines consensus conference on malignant lymphoma 2011 part 1: diffuse
      large B-cell lymphoma (DLBCL), follicular lymphoma (FL) and chronic lymphocytic
      leukemia (CLL).
AB  - To complete the existing treatment guidelines for all tumor types, ESMO organizes
      consensus conferences to better clarify open issues in each disease. In this
      setting, a consensus conference on the management of lymphoma was held on 18 June
      2011 in Lugano, immediately after the end of the 11th International Conference on
      Malignant Lymphoma. The consensus conference convened ~45 experts from all around
      Europe and selected six lymphoma entities to be addressed; for each of them three
      to five open questions were to be discussed by the experts. For each question, a
      recommendation should be given by the panel, supported by the strength of the
      recommendation based on the level of evidence. This consensus report focuses on
      the three most common lymphoproliferative malignancies: diffuse large B-cell
      lymphoma, follicular lymphoma and chronic lymphocytic leukemia. A second report
      will concentrate on mantle cell lymphoma, marginal zone lymphoma and T-cell
      lymphomas.

PMID- 23175627
TI  - Nanomaterial inhalation exposure from nanotechnology-based cosmetic powders: a
      quantitative assessment.
AB  - In this study we quantified exposures to airborne particles ranging from 14 nm to
      20 um due to the use of nanotechnology-based cosmetic powders. Three
      nanotechnology-based and three regular cosmetic powders were realistically
      applied to a mannequin's face while measuring the concentration and size
      distribution of inhaled aerosol particles. Using these data we calculated that
      the highest inhaled particle mass was in the coarse aerosol fraction (2.5-10 um),
      while particles <100 nm made minimal contribution to the inhaled particle mass.
      For all powders, 85-93 % of aerosol deposition occurred in the head airways,
      while <10 % deposited in the alveolar and <5 % in the tracheobronchial regions.
      Electron microscopy data suggest that nanomaterials were likely distributed as
      agglomerates across the entire investigated aerosol size range (14 nm-20 um).
      Thus, investigation of nanoparticle health effects should consider not only the
      alveolar region, but also other respiratory system regions where substantial
      nanomaterial deposition during the actual nanotechnology-based product use would
      occur.

PMID- 23175628
TI  - Rho signalling restriction by the RhoGAP Stard13 integrates growth and
      morphogenesis in the pancreas.
AB  - The development of functional organ architecture relies on coordinated
      morphogenesis and growth. In the developing pancreas, the branching epithelium is
      organised in discrete domains, delineating one specific domain of progenitor
      cells at the tip of the branches. The molecular mechanisms underlying the
      coordinated action of branching and proliferation in organ formation are largely
      unknown. Here, we identify the RhoGAP protein Stard13 as an essential regulator
      of pancreas tissue architecture in the mammalian embryo. Conditional ablation of
      Stard13 expression in the pancreas disrupts epithelial morphogenesis and tip
      domain organisation, resulting in hampered proliferation of tip progenitors and
      subsequent organ hypoplasia. Stard13 acts by regulating Rho signalling spatially
      and temporally during pancreas development. Our findings provide new insights
      into the mechanisms that shape pancreatic epithelium to create a mature organ and
      establish a functional link between Rho-mediated control of epithelial
      remodelling and organ size determination, involving reciprocal interaction of
      actin-MAL/SRF and MAPK signalling pathways.

PMID- 23175629
TI  - The Abelson tyrosine kinase regulates Notch endocytosis and signaling to maintain
      neuronal cell fate in Drosophila photoreceptors.
AB  - The development of a functional organ requires coordinated programs of cell fate
      specification, terminal differentiation and morphogenesis. Whereas signaling
      mechanisms that specify individual cell fates are well documented, little is
      known about the pathways and molecules that maintain these fates stably as normal
      development proceeds or how their dysregulation may contribute to altered cell
      states in diseases such as cancer. In Drosophila, the tyrosine kinase Abelson
      (Abl) interfaces with multiple signaling pathways to direct epithelial and
      neuronal morphogenesis during embryonic and retinal development. Here we show
      that Abl is required for photoreceptor cell fate maintenance, as Abl mutant
      photoreceptors lose neuronal markers during late pupal stages but do not re-enter
      a proliferative state or undergo apoptosis. Failure to maintain the
      differentiated state correlates with impaired trafficking of the Notch receptor
      and ectopic Notch signaling, and can be suppressed by reducing the genetic dose
      of Notch or of its downstream transcriptional effector Suppressor of Hairless.
      Together, these data reveal a novel mechanism for maintaining the terminally
      differentiated state of Drosophila photoreceptors and suggest that neuronal fates
      in the fly retina retain plasticity late into development. Given the general
      evolutionary conservation of developmental signaling mechanisms, Abl-mediated
      regulation of Notch could be broadly relevant to cell fate maintenance and
      reprogramming during normal development, regeneration and oncogenic
      transformation.

PMID- 23175631
TI  - Auxin controls petal initiation in Arabidopsis.
AB  - Floral organs are usually arranged in concentric whorls of sepals, petals,
      stamens and carpels. How founder cells of these organs are specified is unknown.
      In Arabidopsis, the PETAL LOSS (PTL) transcription factor functions in the sepal
      whorl, where it restricts the size of the inter-sepal zone. Genetic evidence
      suggests that PTL acts to support a petal initiation signal active in the
      adjacent whorl. Here we aimed to characterise the signal by identifying enhancers
      that disrupt initiation of the remaining petals in ptl mutants. One such enhancer
      encodes the auxin influx protein AUX1. We have established that auxin is a direct
      and mobile petal initiation signal by promoting its biosynthesis in the inter
      sepal zone in ptl mutant plants and restoring nearby petal initiation. Consistent
      with this, loss of PTL function disrupts DR5 expression, an auxin-inducible
      indicator of petal-initiation sites. The signalling network was extended by
      demonstrating that: (1) loss of RABBIT EARS (RBE) function apparently disrupts
      the same auxin influx process as PTL; (2) the action of AUX1 is supported by
      AXR4, its upstream partner in auxin influx; (3) polar auxin transport, which is
      controlled by PINOID (PID) and PIN-FORMED1 (PIN1), functions downstream of PTL;
      and (4) the action of pmd-1d, a dominant modifier of the ptl mutant phenotype, is
      dependent on auxin transport. Thus, loss of PTL function disrupts auxin dynamics,
      allowing the role of auxin in promoting petal initiation to be revealed.

PMID- 23175630
TI  - A transiently expressed connexin is essential for anterior neural plate
      development in Ciona intestinalis.
AB  - A forward genetic screen in the ascidian Ciona intestinalis identified a mutant
      line (frimousse) with a profound disruption in neural plate development. In
      embryos with the frimousse mutation, the anteriormost neural plate cells, which
      are products of an FGF induction at the blastula and gastrula stages, initially
      express neural plate-specific genes but fail to maintain the induced state and
      ultimately default to epidermis. The genetic lesion in the frimousse mutant lies
      within a connexin gene (cx-11) that is transiently expressed in the developing
      neural plate in a temporal window corresponding to the period of a-lineage neural
      induction. Using a genetically encoded calcium indicator we observed multiple
      calcium transients throughout the developing neural plate in wild-type embryos,
      but not in mutant embryos. A series of treatments at the gastrula and neurula
      stages that block the calcium transients, including gap junction inhibition and
      calcium depletion, were also found to disrupt the development of the anterior
      neural plate in a similar way to the frimousse mutation. The requirement for cx
      11 for anterior neural fate points to a crucial role for intercellular
      communication via gap junctions, probably through mediation of Ca(2+) transients,
      in Ciona intestinalis neural induction.

PMID- 23175632
TI  - In toto live imaging of mouse morphogenesis and new insights into neural tube
      closure.
AB  - In the field of developmental biology, live imaging is a powerful tool for
      studying, in real time, the dynamic behaviors of tissues and cells during organ
      formation. Mammals, which develop in utero, have presented a challenge for live
      imaging. Here, we offer a novel, prolonged and robust live imaging system for
      visualizing the development of a variety of embryonic tissues in the midgestation
      mouse embryo. We demonstrate the advantages of this imaging system by following
      the dynamics of neural tube closure during mouse embryogenesis and reveal
      extensive movements of the cranial neural tissue that are independent of neural
      fold zipping.

PMID- 23175634
TI  - Visualization of cell cycle in mouse embryos with Fucci2 reporter directed by
      Rosa26 promoter.
AB  - Fucci technology makes possible the distinction between live cells in the G(1)
      and S/G(2)/M phases by dual-color imaging. This technology relies upon
      ubiquitylation-mediated proteolysis, and transgenic mice expressing Fucci provide
      a powerful model system with which to study the coordination of the cell cycle
      and development. The mice were initially generated using the CAG promoter; lines
      expressing the G(1) and S/G(2)/M phase probes that emitted orange (mKO2) and
      green (mAG) fluorescence, respectively, were separately constructed. Owing to
      cell type-biased strength of the CAG promoter as well as the positional effects
      of random transgenesis, however, we noticed some variability in Fucci expression
      levels. To control more reliably the expression of cell cycle probes, we used
      different genetic approaches to create two types of reporter mouse lines with
      Fucci2 and Rosa26 transcriptional machinery. Fucci2 is a recently developed Fucci
      derivative, which emits red (mCherry) and green (mVenus) fluorescence and
      provides better color contrast than Fucci. A new transgenic line, R26p-Fucci2,
      utilizes the Rosa26 promoter and harbors the G(1) and S/G(2)/M phase probes in a
      single transgene to preserve their co-inheritance. In the other R26R-Fucci2
      approach, the two probes are incorporated into Rosa26 locus conditionally. The
      Cre-mediated loxP recombination technique thus allows researchers to design cell
      type-specific Fucci2 expression. By performing time-lapse imaging experiments
      using R26p-Fucci2 and R26-Fucci2 in which R26R-Fucci2 had undergone germline loxP
      recombination, we demonstrated the great promise of these mouse reporters for
      studying cell cycle behavior in vivo.

PMID- 23175633
TI  - Hedgehog is required for CySC self-renewal but does not contribute to the GSC
      niche in the Drosophila testis.
AB  - The Drosophila testis harbors two types of stem cells: germ line stem cells
      (GSCs) and cyst stem cells (CySCs). Both stem cell types share a physical niche
      called the hub, located at the apical tip of the testis. The niche produces the
      JAK/STAT ligand Unpaired (Upd) and BMPs to maintain CySCs and GSCs, respectively.
      However, GSCs also require BMPs produced by CySCs, and as such CySCs are part of
      the niche for GSCs. Here we describe a role for another secreted ligand, Hedgehog
      (Hh), produced by niche cells, in the self-renewal of CySCs. Hh signaling cell
      autonomously regulates CySC number and maintenance. The Hh and JAK/STAT pathways
      act independently and non-redundantly in CySC self-renewal. Finally, Hh signaling
      does not contribute to the niche function of CySCs, as Hh-sustained CySCs are
      unable to maintain GSCs in the absence of Stat92E. Therefore, the extended niche
      function of CySCs is solely attributable to JAK/STAT pathway function.

PMID- 23175635
TI  - A continuum of transcriptional identities visualized by combinatorial fluorescent
      in situ hybridization.
AB  - Oligonucleotide-based fluorescent in situ hybridization (FISH) coupled with high
      resolution high-sensitivity microscopy allows the visualization of single RNA
      molecules within fixed cells and tissues as distinct foci. We show here that
      combinatorial labeling of RNA molecules with several fluorescent dyes extends the
      number of genes that can be targeted simultaneously beyond the number of
      fluorophores used. This approach also inherently validates the identification of
      transcripts reducing false positive counts. We have used combinatorial FISH and
      image analysis to measure the transcript densities of six genes using three
      fluorophores. This has allowed us to visualize the endothelial maturation of
      lateral mesoderm in an in vitro ES differentiation assay from a single snapshot
      of molecular identities. Our observations show that, under these specific
      conditions, endothelial maturation follows a homogeneous course with a gradual
      increase in expression of Cdh5 and a concomitant loss of early transcription
      factors, arguing that maturation is governed in a generally deterministic manner.
      This methodology is limited by the number of fluorophores that can be used and by
      the available microscopic resolution, but currently available equipment should
      allow the visualization of transcripts from 10 or more genes simultaneously.

PMID- 23175637
TI  - A Carbonyl Capture Approach for Profiling Oxidized Metabolites in Cell Extracts.
AB  - Fourier-transform ion-cyclotron resonance mass spectrometry (FT-ICR-MS) detection
      of oxidized cellular metabolites is described using isotopologic, carbonyl
      selective derivatizing agents that integrate aminooxy functionality for carbonyl
      capture, quaternary nitrogen for electrospray enhancement, and a hydrophobic
      domain for sample cleanup. These modular structural features enable rapid,
      sensitive analysis of complex mixtures of metabolite-derivatives by FT-ICR-MS via
      continuous nanoelectrospray infusion. Specifically, this approach can be used to
      globally assess levels of low abundance and labile aldehyde and ketone
      metabolites quantitatively and in high throughput manner. These metabolites are
      often key and unique indicators of various biochemical pathways and their
      perturbations. Analysis of lung adenocarcinoma A549 cells established a profile
      of carbonyl metabolites spanning multiple structural classes. We also demonstrate
      a procedure for metabolite quantification using pyruvate as a model analyte.

PMID- 23175636
TI  - Why do cancer patients smoke and what can providers do about it?
AB  - Despite the widespread dissemination of information about the health risks
      associated with smoking, many cancer patients continue to smoke, which results in
      a decreased quality of life, an increased probability of cancer recurrence, and a
      decreased survival time. Efficacious interventions are available to assist cancer
      patients to quit smoking, yet smoking cessation interventions are often not
      implemented. This review describes how clinicians, administrators, insurers, and
      purchasers can encourage a culture of health care in which tobacco cessation
      interventions are implemented consistent with evidenced-based standards of care.
      Implementing efficacious tobacco cessation interventions can reduce morbidity and
      mortality among cancer patients.

PMID- 23175638
TI  - Tension Measurement in Isolated Rat and Mouse Pulmonary Artery.
AB  - Arterial vasoconstriction is an important physiological process in regulating
      blood pressure, and is involved in pathologies. The isolation of arteries from
      rats and mice, as well as the measurement of vascular tension in an ex vivo
      preparation, are important methods in studying the physiology of arteries and the
      pathophysiology associated with arterials. Three major methods to measure
      vascular tension are organ bath, wire myograph, and pressurized arterial
      myograph. The major method to measure vascular remodeling is by observing the
      zero-stress state of an artery.

PMID- 23175639
TI  - ICRP perspective on criteria of acceptability for medical radiological equipment.
AB  - The International Commission on Radiological Protection (ICRP) does not have a
      specific publication or recent detailed advice on acceptability criteria and
      suspension levels for medical radiological equipment. However, a number of the
      Commission's publications clearly stress the need to carry out acceptance testing
      of radiological equipment. Such general recommendations are frequent in earlier
      and recent reports related to external radiation therapy. Over 30 y ago, the ICRP
      even included some examples of parameter accuracies concerning acceptance levels
      in connection with radiotherapy units. Later more general advices related to
      acceptability tests as important parts of various quality assurance programs were
      formulated for radiation therapy as well as for radiodiagnostics without going
      into details to give values for specific parameters. In the radiodiagnostic
      field, there are such general recommendations in reports related to equipment for
      X-ray interventional procedures, digital radiology and computed tomography. The
      ICRP highly supports the elaboration of detailed and clear acceptability and
      suspension criteria for equipment used in medical radiology carried out by
      organisations like International Atomic Energy Agency, International
      Electrotechnical Commission, European Commission, National Electrical
      Manufacturers Association (NEMA, USA) and others and consider such criteria as
      important parts of the quality programmes to guarantee good radiation safety
      conditions for patients in radiation therapy as well as in radiodiagnostics.

PMID- 23175640
TI  - Dental CBCT equipment and performance issues.
AB  - Dental cone beam computed tomography (CBCT), also known as digital volumetric
      tomography was developed in the late 1990s and is now increasingly available in
      clinical practice. It can provide high resolution cross-sectional images of teeth
      and the maxillofacial region with applications in all branches of dentistry. As a
      new imaging modality, there were no established suspension levels at a European
      level. A literature review, encompassing scientific, professional publications
      and existing national guidelines was performed in an attempt to develop a set of
      suspension levels for dental CBCT, using additional expert opinion from the
      members of the European Academy of dento-maxillo-facial radiology. A limited set
      of suspension levels has been devised for aspects of the X-ray tube and
      generator, dosimetry, field-of-view, alignment and image quality. These should be
      kept under review in the light of growing experience of testing equipment in
      practice.

PMID- 23175641
TI  - Introduction to suspension levels: radiotherapy.
AB  - In 2007, the European Commission (EC) commissioned a group of experts to
      undertake the revision of Report Radiation Protection (RP 91) 'Criteria for
      acceptability of radiological (including radiotherapy) and nuclear medicine
      installations' written in 1997. The revised draft report was submitted to the EC
      in 2010, who issued it for public consultation. The EC has commissioned the same
      group of experts to consider the comments of the public consultation for further
      improvement of the revised report. The EC intends to publish the final report
      under its Radiation Report Series as RP 162. This paper describes the background
      to the selection of the key performance parameters for radiotherapy equipment and
      sets out the sources of their criteria of acceptability including suspension
      levels for a wide range of radiotherapy equipment.

PMID- 23175642
TI  - Implementation of acceptability criteria for dental radiology in Belgium.
AB  - The implementation of routine quality control (QC) tests in dental radiology in
      Belgium has been neglected for many years. In 2008, the (Belgian) Federal Agency
      for Nuclear Control determined acceptability criteria for X-ray equipment used
      for dentomaxillofacial imaging. An overview of the development of the criteria,
      together with implementation and the first results of dental QC in Belgium, is
      discussed.

PMID- 23175643
TI  - Automated dispensing and calibration of diagnostic radiopharmaceuticals.
AB  - A real-time automatic dose dispenser (RADD) has been designed and fabricated for
      automatic withdrawal and calibration of diagnostic radiopharmaceuticals such as
      those labelled with (99m)Tc. This system enhances the accuracy and precision of
      activity measurements and reduces personal radiation exposure. The structure,
      function, user-friendliness and performance of this device are described and
      examined for diagnostic activities of (99m)Tc ranging from 50 to 650 MBq. The
      results show that the RADD minimises the likelihood of miscalibration of
      radiopharmaceuticals due to human error and results in significantly reduced
      variability (i.e. higher precision) in dispensed activities of
      radiopharmaceuticals.

PMID- 23175644
TI  - Introduction to suspension levels: nuclear medicine.
AB  - In 2007, the European Commission (EC) commissioned a group of experts to
      undertake the revision of Report Radiation Protection (RP) 91, written in 1997,
      on 'Criteria for acceptability of radiological (including radiotherapy) and
      nuclear medicine installations'. The revised draft report was submitted to the
      EC. Before publication, the EC issued this document for public consultation and
      has commissioned the same group of experts to consider the comments of the public
      consultation in further improving the revised report. The EC intends to publish
      the final report under its Radiation Report Series with the number RP 162. This
      paper introduces the project and presents the methodology adopted to devise the
      criteria of acceptability/suspension levels for nuclear medicine equipment.

PMID- 23175645
TI  - Doses measured using AEC on direct digital radiographic (DDR) X-rays systems:
      updated results with an RP 162 perspective.
AB  - As digital technology in diagnostic radiology systems becomes more prevalent,
      there is a need to provide comparative dose information for these new systems.
      This is needed in particular for testing the automatic exposure control (AEC)
      devices on direct digital radiography (DDR) systems as there is no consensus on
      the receptor dose level in the current guidelines. The new European Commission RP
      162 document sets the suspension level for the 'verification of kerma at receptor
      entrance in computed radiography and DDR systems under AEC' as >=10 uGy. This
      document also notes that alternate methodologies are acceptable, and may require
      adjustment in the suspension level if used. This study provides a range of
      typical doses under AEC for DDR systems, for a variety measurement methodologies,
      including that described in RP 162.

PMID- 23175647
TI  - Protracted bacterial bronchitis: reinventing an old disease.
AB  - Chronic cough is common in the paediatric population, yet the true prevalence of
      this condition remains difficult to define. Protracted bacterial bronchitis (PBB)
      is a disease caused by the chronic infection of the conducting airways. In many
      children the condition appears to be secondary to impaired mucociliary clearance
      that creates a niche for bacteria to become established, probably in the form of
      biofilms. In others, immunodeficiencies, which may be subtle, appear to be a
      factor. PBB causes persistent coughing and disturbed sleep, and affects exercise
      tolerance, causing significant levels of morbidity. PBB has remained largely
      unrecognised and is often misdiagnosed as asthma.

PMID- 23175646
TI  - A novel hypothesis: regulatory B lymphocytes shape outcome from experimental
      stroke.
AB  - Although inflammatory immune cells clearly contribute to the development of
      middle cerebral artery occlusion (MCAO) in mice, the failure to block neutrophil
      associated injury in clinical stroke trials has discouraged further development
      of immunotherapeutic approaches. However, there is renewed interest in a possible
      protective role for regulatory T- and B-cells that can suppress inflammation and
      limit central nervous system damage induced by infiltrating pro-inflammatory
      cells. Our failure to implicate CD4(+)FoxP3(+) T-cells in limiting brain lesion
      volume after MCAO turned our focus towards regulatory B-cells known to mediate
      protection against other inflammatory CNS conditions. Our results clearly
      demonstrated that B-cell deficient mice developed larger infarct volumes, higher
      mortality and more severe functional deficits compared to wild-type mice, and had
      increased numbers of activated T-cells, macrophages, microglial cells, and
      neutrophils in the affected brain hemisphere. These MCAO-induced changes were
      completely prevented in B-cell-restored mice after transfer of highly purified WT
      B-cells but not IL-10-deficient B-cells. Our novel observations are the first to
      implicate IL-10-secreting B-cells as a major regulatory cell type in stroke and
      suggest that enhancement of regulatory B-cells might have application as a novel
      therapy for this devastating neurologic condition. 

PMID- 23175648
TI  - A Bilingual Advantage for Episodic Memory in Older Adults.
AB  - The ability to remember events - referred to as episodic memory - is typically
      subject to decline in older adulthood. Episodic memory decline has been
      attributed in part to less successful executive functioning, which may hinder an
      older adult's ability to implement controlled encoding and retrieval processes.
      Since bilingual older adults often show more successful executive functioning
      than monolinguals, they may be better able to maintain episodic memory. To
      examine this hypothesis, we compared bilingual and monolingual older adults on a
      picture scene recall task (assessing episodic memory) and a Simon task (assessing
      executive functioning). Bilinguals exhibited better episodic memory than their
      monolingual peers, recalling significantly more items overall. Within the
      bilingual group, earlier second language acquisition and more years speaking two
      languages were associated with better recall. Bilinguals also demonstrated higher
      executive functioning, and there was evidence that level of executive functioning
      was related to memory performance. Results indicate that extensive practice
      controlling two languages may benefit episodic memory in older adults.

PMID- 23175649
TI  - Mutagenesis and modeling to predict structural and functional characteristics of
      the Staphylococcus aureus MepA multidrug efflux pump.
AB  - MepA is a multidrug and toxin extrusion (MATE) family protein and the only MATE
      protein encoded within the Staphylococcus aureus genome. Structural data for MATE
      proteins are limited to a single high-resolution example, NorM of Vibrio
      cholerae. Substitution mutations were created in MepA using gradient plates
      containing both a substrate and reserpine as an efflux pump inhibitor. Site
      directed mutagenesis of plasmid-based mepA was used to reproduce these mutations,
      as well as unique or low-frequency mutations identified in mepA-overexpressing
      clinical strains, and to mutagenize conserved acidic residues. The effect of
      these changes on protein function was quantitated in a norA-disrupted host strain
      by susceptibility testing with and without inhibitors and by determining the
      proficiency of ethidium efflux. Up-function substitutions clustered in the
      carboxy half of MepA, near the cytoplasmic face of the protein. Repeated
      application of the same gradient plate conditions frequently reproduced identical
      substitution mutations, suggesting that individual residues are required for
      interaction with specific substrates. Acidic residues critical to protein
      function were identified in helices 4 and 5. In silico modeling revealed an
      outward-facing molecule, with helices 1, 2, 4, 7, 8, and 10 having contact with a
      central cavity that may represent a substrate translocation pathway. Functionally
      important residues within this cavity included S81, A161, M291, and A302. These
      data provide a critical starting point for understanding how MATE multidrug
      efflux proteins function and will be useful in refining crystallographic data
      when they are available.

PMID- 23175650
TI  - Osmotic control of opuA expression in Bacillus subtilis and its modulation in
      response to intracellular glycine betaine and proline pools.
AB  - Glycine betaine is an effective osmoprotectant for Bacillus subtilis. Its import
      into osmotically stressed cells led to the buildup of large pools, whose size was
      sensitively determined by the degree of the osmotic stress imposed. The amassing
      of glycine betaine caused repression of the formation of an osmostress-adaptive
      pool of proline, the only osmoprotectant that B. subtilis can synthesize de novo.
      The ABC transporter OpuA is the main glycine betaine uptake system of B.
      subtilis. Expression of opuA was upregulated in response to both sudden and
      sustained increases in the external osmolarity. Nonionic osmolytes exerted a
      stronger inducing effect on transcription than ionic osmolytes, and this was
      reflected in the development of corresponding OpuA-mediated glycine betaine
      pools. Primer extension analysis and site-directed mutagenesis pinpointed the
      osmotically controlled opuA promoter. Deviations from the consensus sequence of
      SigA-type promoters serve to keep the transcriptional activity of the opuA
      promoter low in the absence of osmotic stress. opuA expression was downregulated
      in a finely tuned manner in response to increases in the intracellular glycine
      betaine pool, regardless of whether this osmoprotectant was imported or was newly
      synthesized from choline. Such an effect was also exerted by carnitine, an
      effective osmoprotectant for B. subtilis that is not a substrate for the OpuA
      transporter. opuA expression was upregulated in a B. subtilis mutant that was
      unable to synthesize proline in response to osmotic stress. Collectively, our
      data suggest that the intracellular solute pool is a key determinant for the
      osmotic control of opuA expression.

PMID- 23175651
TI  - DEAD-Box RNA helicases in Bacillus subtilis have multiple functions and act
      independently from each other.
AB  - DEAD-box RNA helicases play important roles in remodeling RNA molecules and in
      facilitating a variety of RNA-protein interactions that are key to many essential
      cellular processes. In spite of the importance of RNA, our knowledge about RNA
      helicases is limited. In this study, we investigated the role of the four DEAD
      box RNA helicases in the Gram-positive model organism Bacillus subtilis. A strain
      deleted of all RNA helicases is able to grow at 37 degrees C but not at lower
      temperatures. The deletion of cshA, cshB, or yfmL in particular leads to cold
      sensitive phenotypes. Moreover, these mutant strains exhibit unique defects in
      ribosome biogenesis, suggesting distinct functions for the individual enzymes in
      this process. Based on protein accumulation, severity of the cold-sensitive
      phenotype, and the interaction with components of the RNA degradosome, CshA is
      the major RNA helicase of B. subtilis. To unravel the functions of CshA in
      addition to ribosome biogenesis, we conducted microarray analysis and identified
      the ysbAB and frlBONMD mRNAs as targets that are strongly affected by the
      deletion of the cshA gene. Our findings suggest that the different helicases make
      distinct contributions to the physiology of B. subtilis. Ribosome biogenesis and
      RNA degradation are two of their major tasks in B. subtilis.

PMID- 23175652
TI  - Impact of Lactobacillus plantarum sortase on target protein sorting,
      gastrointestinal persistence, and host immune response modulation.
AB  - Sortases are transpeptidases that couple surface proteins to the peptidoglycan of
      Gram-positive bacteria, and several sortase-dependent proteins (SDPs) have been
      demonstrated to be crucial for the interactions of pathogenic and nonpathogenic
      bacteria with their hosts. Here, we studied the role of sortase A (SrtA) in
      Lactobacillus plantarum WCFS1, a model Lactobacillus for probiotic organisms. An
      isogenic srtA deletion derivative was constructed which did not show residual
      SrtA activity. DNA microarray-based transcriptome analysis revealed that the srtA
      deletion had only minor impact on the full-genome transcriptome of L. plantarum,
      while the expression of SDP-encoding genes remained completely unaffected. Mass
      spectrometry analysis of the bacterial cell surface proteome, which was assessed
      by trypsinization of intact bacterial cells and by LiCl protein extraction,
      revealed that SrtA is required for the appropriate subcellular location of
      specific SDPs and for their covalent coupling to the cell envelope, respectively.
      We further found that SrtA deficiency did not affect the persistence and/or
      survival of L. plantarum in the gastrointestinal tract of mice. In addition, an
      in vitro immature dendritic cell (iDC) assay revealed that the removal of surface
      proteins by LiCl strongly affected the proinflammatory signaling properties of
      the SrtA-deficient strain but not of the wild type, which suggests a role of SDPs
      in host immune response modulation.

PMID- 23175655
TI  - Lessons from the recent twin earthquakes in Iran.

PMID- 23175654
TI  - The structure of the CS1 pilus of enterotoxigenic Escherichia coli reveals
      structural polymorphism.
AB  - Enterotoxigenic Escherichia coli (ETEC) is a bacterial pathogen that causes
      diarrhea in children and travelers in developing countries. ETEC adheres to host
      epithelial cells in the small intestine via a variety of different pili. The CS1
      pilus is a prototype for a family of related pili, including the CFA/I pili,
      present on ETEC and other Gram-negative bacterial pathogens. These pili are
      assembled by an outer membrane usher protein that catalyzes subunit
      polymerization via donor strand complementation, in which the N terminus of each
      incoming pilin subunit fits into a hydrophobic groove in the terminal subunit,
      completing a beta-sheet in the Ig fold. Here we determined a crystal structure of
      the CS1 major pilin subunit, CooA, to a 1.6-A resolution. CooA is a globular
      protein with an Ig fold and is similar in structure to the CFA/I major pilin
      CfaB. We determined three distinct negative-stain electron microscopic
      reconstructions of the CS1 pilus and generated pseudoatomic-resolution pilus
      structures using the CooA crystal structure. CS1 pili adopt multiple structural
      states with differences in subunit orientations and packing. We propose that the
      structural perturbations are accommodated by flexibility in the N-terminal donor
      strand of CooA and by plasticity in interactions between exposed flexible loops
      on adjacent subunits. Our results suggest that CS1 and other pili of this class
      are extensible filaments that can be stretched in response to mechanical stress
      encountered during colonization.

PMID- 23175653
TI  - Multiple factors modulate biofilm formation by the anaerobic pathogen Clostridium
      difficile.
AB  - Bacteria within biofilms are protected from multiple stresses, including immune
      responses and antimicrobial agents. The biofilm-forming ability of bacterial
      pathogens has been associated with increased antibiotic resistance and chronic
      recurrent infections. Although biofilms have been well studied for several gut
      pathogens, little is known about biofilm formation by anaerobic gut species. The
      obligate anaerobe Clostridium difficile causes C. difficile infection (CDI), a
      major health care-associated problem primarily due to the high incidence of
      recurring infections. C. difficile colonizes the gut when the normal intestinal
      microflora is disrupted by antimicrobial agents; however, the factors or
      processes involved in gut colonization during infection remain unclear. We
      demonstrate that clinical C. difficile strains, i.e., strain 630 and the
      hypervirulent strain R20291, form structured biofilms in vitro, with R20291
      accumulating substantially more biofilm. Microscopic and biochemical analyses
      show multiple layers of bacteria encased in a biofilm matrix containing proteins,
      DNA, and polysaccharide. Employing isogenic mutants, we show that virulence
      associated proteins, Cwp84, flagella, and a putative quorum-sensing regulator,
      LuxS, are all required for maximal biofilm formation by C. difficile.
      Interestingly, a mutant in Spo0A, a transcription factor that controls spore
      formation, was defective for biofilm formation, indicating a possible link
      between sporulation and biofilm formation. Furthermore, we demonstrate that
      bacteria in clostridial biofilms are more resistant to high concentrations of
      vancomycin, a drug commonly used for treatment of CDI. Our data suggest that
      biofilm formation by C. difficile is a complex multifactorial process and may be
      a crucial mechanism for clostridial persistence in the host.

PMID- 23175657
TI  - Safety of ovarian autotransplantation.

PMID- 23175656
TI  - Mechanistic insights into the regulation of circular dorsal ruffle formation.
AB  - Growth factor stimulations induce dynamic changes in the cytoskeleton beneath the
      plasma membrane. Among them is the formation of membrane ruffles organized in a
      circular array, called 'circular dorsal ruffles' (CDRs). Physiological functions
      of CDRs include downregulation of cell growth by desensitizing the signalling
      from growth factor receptors as well as rearrangement of adhesion sites at the
      onset of cell migration. For the formation of CDRs, not only the activators of
      actin polymerization, such as N-WASP and the Arp2/3-complex, but also membrane
      deforming proteins with BAR/F-BAR domains are necessary. Small GTPases are also
      involved in the formation of CDRs by controlling intracellular trafficking
      through endosomes. Moreover, recent analyses of another circular cytoskeletal
      structure, podosome rosettes, have revealed common molecular features shared with
      CDRs. Among them, the roles of PI3-kinase and phosphoinositide 5-phosphatase may
      hold the key to the induction of these circular structures.

PMID- 23175658
TI  - Haplo-BMT: cure or back to sickle cell?

PMID- 23175659
TI  - Addressing the envelope for gene delivery.

PMID- 23175660
TI  - Stem cells need their T.

PMID- 23175661
TI  - Clone wars: IgH subclones in preB-ALL.

PMID- 23175662
TI  - Episomal amplification of NUP214-ABL1 fusion gene in B-cell acute lymphoblastic
      leukemia.

PMID- 23175663
TI  - Role of fecal calprotectin as biomarker of gastrointestinal GVHD after allogeneic
      stem cell transplantation.

PMID- 23175664
TI  - High-dose melphalan and stem cell transplantation for patients with AL
      amyloidosis: trends in treatment-related mortality over the past 17 years at a
      single referral center.

PMID- 23175666
TI  - Intraindividual and interindividual variabilities in endogenous cortisol 6beta
      hydroxylation clearance as an index for in vivo CYP3A phenotyping in humans.
AB  - This study was designed to evaluate the in vivo activity of cytochrome P450 3A
      (CYP3A) in 49 healthy Japanese subjects aged 22-58 years using endogenous
      cortisol 6beta-hydroxylation clearance [CLm(6beta)], a novel biomarker for CYP3A
      phenotyping. CLm(6beta) in the 49 healthy subjects was 2.40 +/- 0.79 ml/min with
      an approximately 4-fold interindividual variability of CYP3A activity. The mean
      clearance in the 24 women was 2.50 +/- 0.89 ml/min; the value in the women was
      higher than in the 25 men (2.30 +/- 0.69 ml/min) by approximately 9%. We also
      measured the change of CLm(6beta) in 14 healthy subjects in the morning at 10:00
      12:00 every 2 or 3 days over a period of 36-53 days and observed a 1.5-fold to
      3.4-fold day-to-day intraindividual variability in the CYP3A activity. The mean
      value for CLm(6beta) in each subject for 36-53 days was 2.54 +/- 0.76 ml/min (n =
      14). We also evaluated the CLm(6beta) every 2 hours from 8:00-20:00 in 26 healthy
      subjects. The within-day intraindividual clearance variability was 1.1-fold to
      2.5-fold (2.45 +/- 0.91 ml/min, n = 26). No characteristic diurnal rhythms were
      observed in the in vivo activity of CYP3A.

PMID- 23175667
TI  - Increased hospital stay and allograft dysfunction in renal transplant recipients
      with Cyp2c19 AA variant in SNP rs4244285.
AB  - Pharmacogenetics correlates certain genetic variants, such as single nucleotide
      polymorphisms (SNPs), with blood drug levels, efficacy, and adverse effects of
      the treatment. Tacrolimus is mainly metabolized via CYP3A4/5, whereas CYP2C19 and
      CYP3A4/5 are responsible for omeprazole metabolism. Omeprazole inhibits
      tacrolimus metabolism via CYP3A5 in patients carrying variant alleles of CYP2C19,
      increasing tacrolimus blood concentrations. Seventy-five renal transplant
      recipients treated with tacrolimus and concomitant omeprazole were genotyped in a
      panel of 37 SNPs with use of Sequenom MassArray. The patients with CYP2C19*2/*2
      genotype (n = 4) showed a median posttransplantation hospital stay of 27.5 days
      (95% confidence interval [CI], 23-39 days), compared with 12 days (95% CI, 10-15
      days) in patients with CYP2C19*1/*1 or CYP2C19*1/*2 (n = 71; P = 0.016, Kruskal
      Wallis test).The difference in hospital stay was directly correlated with an
      increase in tacrolimus levels (C(min)/[dose/weight]) during the first week after
      trasplantation (in 59 patients with data on levels; P = 0.021, Kruskal-Wallis),
      excluding the patients with atypical metabolisms due to CYP3A5*1/*3 or
      CYP3A5*1/*1 genotype. Recipients with CYP2C19*2/*2 genotype also showed allograft
      delayed function (acute tubular necrosis in 3 patients). Genotyping of CYP3A5 and
      CYP2C19 in renal transplantation should be considered to be of interest when
      treating with tacrolimus and omeprazole, because CYP2C19*2/*2 variant indirectly
      elicits an increase of tacrolimus blood levels and, in our study population, the
      adverse effects described.

PMID- 23175668
TI  - Gestational age-dependent changes in gene expression of metabolic enzymes and
      transporters in pregnant mice.
AB  - Pregnancy-induced changes in drug pharmacokinetics can be explained by changes in
      expression of drug-metabolizing enzymes and transporters and/or normal
      physiology. In this study, we determined gestational age-dependent expression
      profiles for all metabolic enzyme and transporter genes in the maternal liver,
      kidney, small intestine, and placenta of pregnant mice by microarray analysis. We
      specifically examined the expression of genes important for xenobiotic, bile
      acid, and steroid hormone metabolism and disposition, namely, cytochrome P450s
      (Cyp), UDP-glucuronosyltranserases (Ugt), sulfotransferases (Sult), and ATP
      binding cassette (Abc), solute carrier (Slc), and solute carrier organic anion
      (Slco) transporters. Few Ugt and Sult genes were affected by pregnancy. Cyp17a1
      expression in the maternal liver increased 3- to 10-fold during pregnancy, which
      was the largest observed change in the maternal tissues. Cyp1a2, most Cyp2
      isoforms, Cyp3a11, and Cyp3a13 expression in the liver decreased on gestation
      days (gd) 15 and 19 compared with nonpregnant controls (gd 0). In contrast,
      Cyp2d40, Cyp3a16, Cyp3a41a, Cyp3a41b, and Cyp3a44 in the liver were induced
      throughout pregnancy. In the placenta, Cyp expression on gd 10 and 15 was
      upregulated compared with gd 19. Notable changes were also observed in Abc and
      Slc transporters. Abcc3 expression in the liver and Abcb1a, Abcc4, and Slco4c1
      expression in the kidney were downregulated on gd 15 and 19. In the placenta,
      Slc22a3 (Oct3) expression on gd 10 was 90% lower than that on gd 15 and 19. This
      study demonstrates important gestational age-dependent expression of metabolic
      enzyme and transporter genes, which may have mechanistic relevance to drug
      disposition in human pregnancy.

PMID- 23175670
TI  - Volatile fingerprints of seeds of four species indicate the involvement of
      alcoholic fermentation, lipid peroxidation, and Maillard reactions in seed
      deterioration during ageing and desiccation stress.
AB  - The volatile compounds released by orthodox (desiccation-tolerant) seeds during
      ageing can be analysed using gas chromatography-mass spectrometry (GC-MS).
      Comparison of three legume species (Pisum sativum, Lathyrus pratensis, and
      Cytisus scoparius) during artificial ageing at 60% relative humidity and 50 
      degrees C revealed variation in the seed volatile fingerprint between species,
      although in all species the overall volatile concentration increased with storage
      period, and changes could be detected prior to the onset of viability loss. The
      volatile compounds are proposed to derive from three main sources: alcoholic
      fermentation, lipid peroxidation, and Maillard reactions. Lipid peroxidation was
      confirmed in P. sativum seeds through analysis of malondialdehyde and 4
      hydroxynonenal. Volatile production by ageing orthodox seeds was compared with
      that of recalcitrant (desiccation-sensitive) seeds of Quercus robur during
      desiccation. Many of the volatiles were common to both ageing orthodox seeds and
      desiccating recalcitrant seeds, with alcoholic fermentation forming the major
      source of volatiles. Finally, comparison was made between two methods of
      analysis; the first used a Tenax adsorbent to trap volatiles, whilst the second
      used solid phase microextraction to extract volatiles from the headspace of vials
      containing powdered seeds. Solid phase microextraction was found to be more
      sensitive, detecting a far greater number of compounds. Seed volatile analysis
      provides a non-invasive means of characterizing the processes involved in seed
      deterioration, and potentially identifying volatile marker compounds for the
      diagnosis of seed viability loss.

PMID- 23175669
TI  - DNA methylation dynamics and MET1a-like gene expression changes during stress
      induced pollen reprogramming to embryogenesis.
AB  - Stress-induced plant cell reprogramming involves changes in global genome
      organization, being the epigenetic modifications key factors in the regulation of
      genome flexibility. DNA methylation, accomplished by DNA methyltransferases,
      constitutes a prominent epigenetic modification of the chromatin fibre which is
      locked in a transcriptionally inactive conformation. Changes in DNA methylation
      accompany the reorganization of the nuclear architecture during plant cell
      differentiation and proliferation. After a stress treatment, in vitro-cultured
      microspores are reprogrammed and change their gametophytic developmental pathway
      towards embryogenesis, the process constituting a useful system of reprogramming
      in isolated cells for applied and basic research. Gene expression driven by
      developmental and stress cues often depends on DNA methylation; however, global
      DNA methylation and genome-wide expression patterns relationship is still poorly
      understood. In this work, the dynamics of DNA methylation patterns in relation to
      nuclear architecture and the expression of BnMET1a-like DNA methyltransferase
      genes have been analysed during pollen development and pollen reprogramming to
      embryogenesis in Brassica napus L. by a multidisciplinary approach. Results
      showed an epigenetic reprogramming after microspore embryogenesis induction which
      involved a decrease of global DNA methylation and its nuclear redistribution with
      the change of developmental programme and the activation of cell proliferation,
      while DNA methylation increases with pollen and embryo differentiation in a cell
      type-specific manner. Changes in the presence, abundance, and distribution of
      BnMET1a-like transcripts highly correlated with variations in DNA methylation.
      Mature zygotic and pollen embryos presented analogous patterns of DNA methylation
      and MET1a-like expression, providing new evidence of the similarities between
      both developmental embryogenic programmes.

PMID- 23175672
TI  - Association between interleukin-6 levels and first-ever cerebrovascular events in
      patients with vascular risk factors.
AB  - OBJECTIVE: The objective of this study was to examine the association of
      inflammatory markers with risk of first-ever cerebrovascular events (CVEs), while
      simultaneously evaluating subclinical vascular disease. METHODS AND RESULTS: We
      enrolled 464 outpatients who had vascular risk factors without any preexisting
      cardiovascular disease. We examined the presence of silent lacunar infarction
      (SLI) by magnetic resonance imaging; carotid intima-media thickness by
      ultrasound; and measured high-sensitivity C-reactive protein, interleukin (IL)-6,
      and IL-18 at baseline, and assessed their associations with CVEs using Cox
      proportional hazards models of 4.8+/-2.6 years follow-up. We further calculated
      measures of reclassification and discrimination. In age- and sex-adjusted
      analysis, IL-6, but neither high-sensitivity C-reactive protein nor IL-18, was
      associated with CVEs. The association remained significant after adjustment for
      conventional risk factors, intima-media thickness, and SLI (hazard ratios: 1.80,
      per 1-SD increase in log IL-6, P=0.03). Compared with the patients with below
      median IL-6 without SLI, those with above median IL-6 and SLI had a higher risk
      of CVEs (hazard ratios: 4.14, P=0.0014). The combination of IL-6 and SLI resulted
      in the net reclassification improvement of 14.3% (P=0.04), and the integrated
      discrimination improvement gain of 2.1% (P=0.05). CONCLUSIONS: IL-6 levels were
      independently associated with CVEs and could improve reclassification in those
      with SLI.

PMID- 23175671
TI  - Gibberellins regulate the transcription of the continuous flowering regulator,
      RoKSN, a rose TFL1 homologue.
AB  - The role of gibberellins (GAs) during floral induction has been widely studied in
      the annual plant Arabidopsis thaliana. Less is known about this control in
      perennials. It is thought that GA is a major regulator of flowering in rose. In
      spring, low GA content may be necessary for floral initiation. GA inhibited
      flowering in once-flowering roses, whereas GA did not block blooming in
      continuous-flowering roses. Recently, RoKSN, a homologue of TFL1, was shown to
      control continuous flowering. The loss of RoKSN function led to continuous
      flowering behaviour. The objective of this study was to understand the molecular
      control of flowering by GA and the involvement of RoKSN in this inhibition. In
      once-flowering rose, the exogenous application of GA(3) in spring inhibited
      floral initiation. Application of GA(3) during a short period of 1 month,
      corresponding to the floral transition, was sufficient to inhibit flowering. At
      the molecular level, RoKSN transcripts were accumulated after GA(3) treatment. In
      spring, this accumulation is correlated with floral inhibition. Other floral
      genes such as RoFT, RoSOC1, and RoAP1 were repressed in a RoKSN-dependent
      pathway, whereas RoLFY and RoFD repression was RoKSN independent. The RoKSN
      promoter contained GA-responsive cis-elements, whose deletion suppressed the
      response to GA in a heterologous system. In summer, once-flowering roses did not
      flower even after exogenous application of a GA synthesis inhibitor that failed
      to repress RoKSN. A model is presented for the GA inhibition of flowering in
      spring mediated by the induction of RoKSN. In summer, factors other than GA may
      control RoKSN.

PMID- 23175673
TI  - Estrogen receptor-mediated regulation of microRNA inhibits proliferation of
      vascular smooth muscle cells.
AB  - OBJECTIVE: Estradiol (E2) regulates gene transcription by activating estrogen
      receptor-alpha and estrogen receptor-beta. Many of the genes regulated by E2 via
      estrogen receptors are repressed, yet the molecular mechanisms that mediate E2
      induced gene repression are currently unknown. We hypothesized that E2, acting
      through estrogen receptors, regulates expression of microRNAs (miRs) leading to
      repression of expression of specific target genes. METHODS AND RESULTS: Here, we
      report that E2 significantly upregulates the expression of 26 miRs and
      downregulates the expression of 6 miRs in mouse aorta. E2-mediated upregulation
      of one of these miRs, miR-203, was chosen for further study. In cultured vascular
      smooth muscle cells (VSMC), E2-mediated upregulation of miR-203 is mediated by
      estrogen receptor-alpha (but not estrogen receptor-beta) via transcriptional
      upregulation of the primary miR. We demonstrate that the transcription factors
      Zeb-1 and AP-1 play critical roles in mediating E2-induced upregulation of miR
      203 transcription. We show further that miR-203 mediates E2-induced repression of
      Abl1, and p63 protein abundance in VSMC. Finally, knocking-down miR-203 abolishes
      E2-mediated inhibition of VSMC proliferation, and overexpression of miR-203
      inhibits cultured VSMC proliferation, but not vascular endothelial cell
      proliferation. CONCLUSIONS: Our findings demonstrate that E2 regulates expression
      of miRs in the vasculature and support the estrogen receptors-dependent induction
      of miRs as a mechanism for E2-mediated gene repression. Furthermore, our findings
      demonstrate that miR-203 contributes to E2-induced inhibition of VSMC
      proliferation and highlight the potential of miR-203 as a therapeutic agent in
      the treatment of proliferative cardiovascular diseases.

PMID- 23175674
TI  - Pioglitazone slows progression of atherosclerosis in prediabetes independent of
      changes in cardiovascular risk factors.
AB  - OBJECTIVE: To determine whether changes in standard and novel risk factors during
      the Actos Now for Prevention of Diabetes trial explained the slower rate of
      carotid intima media thickness (CIMT) progression with pioglitazone treatment in
      persons with prediabetes. METHODS AND RESULTS: CIMT was measured in 382
      participants at the beginning and up to 3 additional times during follow-up of
      the Actos Now for Prevention of Diabetes trial. During an average follow-up of
      2.3 years, the mean unadjusted annual rate of CIMT progression was significantly
      (P=0.01) lower with pioglitazone treatment (4.76*10(-3) mm/year; 95% CI: 2.39*10(
      3)-7.14*10(-3) mm/year) compared with placebo (9.69*10(-3) mm/year; 95% CI:
      7.24*10(-3)-12.15*10(-3) mm/year). High-density lipoprotein cholesterol, fasting
      and 2-hour glucose, HbA(1c), fasting insulin, Matsuda insulin sensitivity index,
      adiponectin, and plasminogen activator inhibitor-1 levels improved significantly
      with pioglitazone treatment compared with placebo (P<0.001). However, the effect
      of pioglitazone on CIMT progression was not attenuated by multiple methods of
      adjustment for traditional, metabolic, and inflammatory risk factors and
      concomitant medications, and was independent of changes in risk factors during
      pioglitazone treatment. CONCLUSIONS: Pioglitazone slowed progression of CIMT,
      independent of improvement in hyperglycemia, insulin resistance, dyslipidemia,
      and systemic inflammation in prediabetes. These results suggest a possible direct
      vascular benefit of pioglitazone.

PMID- 23175675
TI  - Mitogen-activated protein kinase 14 is a novel negative regulatory switch for the
      vascular smooth muscle cell contractile gene program.
AB  - OBJECTIVE: Several studies have shown through chemical inhibitors that p38
      mitogen-activated protein kinase (MAPK) promotes vascular smooth muscle cell
      (VSMC) differentiation. Here, we evaluate the effects of knocking down a dominant
      p38MAPK isoform on VSMC differentiation. METHODS AND RESULTS: Knockdown of
      p38MAPKalpha (MAPK14) in human coronary artery SMCs unexpectedly increases VSMC
      differentiation genes, such as miR145, ACTA2, CNN1, LMOD1, and TAGLN, with little
      change in the expression of serum response factor (SRF) and 2 SRF cofactors,
      myocardin (MYOCD) and myocardin-related transcription factor A (MKL1). A variety
      of chemical and biological inhibitors demonstrate a critical role for a RhoA-MKL1
      SRF-dependent pathway in mediating these effects. MAPK14 knockdown promotes MKL1
      nuclear localization and VSMC marker expression, an effect partially reversed
      with Y27632; in contrast, MAP2K6 (MKK6) blocks MKL1 nuclear import and VSMC
      marker expression. Immunostaining and Western blotting of injured mouse carotid
      arteries reveal elevated MAPK14 (both total and phosphorylated) and reduced VSMC
      marker expression. CONCLUSIONS: Reduced MAPK14 expression evokes unanticipated
      increases in VSMC contractile genes, suggesting an unrecognized negative
      regulatory role for MAPK14 signaling in VSMC differentiation.

PMID- 23175676
TI  - Influence of trait behavioral inhibition and behavioral approach motivation
      systems on the LPP and frontal asymmetry to anger pictures.
AB  - Behavioral approach and avoidance are fundamental to the experience of emotion
      and motivation, but the motivational system associated with anger is not well
      established. Some theories posit that approach motivational processes underlie
      anger, whereas others posit that avoidance motivational processes underlie anger.
      The current experiment sought to address whether traits related to behavioral
      approach or avoidance influence responses to anger stimuli using multiple
      measures: ERP, electroencephalographic (EEG) alpha-asymmetry and self-report.
      After completing the behavioral inhibition system/behavioral approach system
      (BIS/BAS) scales, participants viewed anger pictures and neutral pictures. BAS
      predicted larger late positive potentials (LPPs) to anger pictures, but not to
      neutral pictures. In addition, BAS predicted greater left-frontal asymmetry to
      anger pictures. Moreover, larger LPPs to anger pictures related to greater left
      frontal EEG asymmetry during anger pictures. These results suggest that trait
      approach motivation relates to neurophysiological responses of anger. 

PMID- 23175678
TI  - The role of the medial prefrontal cortex in social categorization.
AB  - Group membership is an important aspect of our everyday behavior. Recently, we
      showed that existing relevant in-group labels increased activation in the medial
      prefrontal cortex (MPFC) compared with out-group labels, suggesting a role of the
      MPFC in social categorization. However, the question still remains whether this
      increase in MPFC activation for in-group representation is solely related with
      previous experience with the in-group. To test this, we randomly assigned
      participants to a red or blue team and in a subsequent functional magnetic
      resonance imaging experiment they categorized red and blue team words as
      belonging to either the in-group or the out-group. Results showed that even under
      these minimal conditions increased activation was found in the MPFC when
      participants indicated that they belonged to a group, as compared with when they
      did not. This effect was found to be associated with the level of group
      identification. These results confirm the role of MPFC in social categorization. 

PMID- 23175679
TI  - Moral concerns increase attention and response monitoring during IAT performance:
      ERP evidence.
AB  - Previous research has revealed that people value morality as a more important
      person characteristic than competence. In this study, we tested whether people
      adjust their less explicit behavior more to moral than competence values.
      Participants performed an Implicit Association Test (IAT) that was either framed
      as a test of their morality or as a test of their competence. The behavioral
      results revealed a smaller IAT effect (i.e. a weaker negative implicit bias
      toward Muslims) in the morality condition than in the competence condition.
      Moreover, event-related potentials indicated increased social categorization of
      faces (as indexed by the N1 and P150) and enhanced conflict- and error monitoring
      (N450 and error-related negativity) in the morality condition compared to the
      competence condition. These findings indicate that an emphasis on morality can
      increase attentional and motivational processes that help to improve people's
      task performance. 

PMID- 23175677
TI  - Hormonal contraceptives, menstrual cycle and brain response to faces.
AB  - Both behavioral and neuroimaging evidence support a female advantage in the
      perception of human faces. Here we explored the possibility that this
      relationship may be partially mediated by female sex hormones by investigating
      the relationship between the brain's response to faces and the use of oral
      contraceptives, as well as the phase of the menstrual cycle. First, functional
      magnetic resonance images were acquired in 20 young women [10 freely cycling and
      10 taking oral contraception (OC)] during two phases of their cycle: mid-cycle
      and menstruation. We found stronger neural responses to faces in the right
      fusiform face area (FFA) in women taking oral contraceptives (vs freely cycling
      women) and during mid-cycle (vs menstruation) in both groups. Mean blood
      oxygenation level-dependent response in both left and right FFA increased as
      function of the duration of OC use. Next, this relationship between the use of OC
      and FFA response was replicated in an independent sample of 110 adolescent girls.
      Finally in a parallel behavioral study carried out in another sample of women, we
      found no evidence of differences in the pattern of eye movements while viewing
      faces between freely cycling women vs those taking oral contraceptives. The
      imaging findings might indicate enhanced processing of social cues in women
      taking OC and women during mid-cycle. 

PMID- 23175681
TI  - Controlling bizarre delusions.

PMID- 23175682
TI  - Working the fundamentals.

PMID- 23175680
TI  - Identifying miRNAs, targets and functions.
AB  - microRNAs (miRNAs) are small endogenous non-coding RNAs that function as the
      universal specificity factors in post-transcriptional gene silencing. Discovering
      miRNAs, identifying their targets and further inferring miRNA functions have been
      a critical strategy for understanding normal biological processes of miRNAs and
      their roles in the development of disease. In this review, we focus on
      computational methods of inferring miRNA functions, including miRNA functional
      annotation and inferring miRNA regulatory modules, by integrating heterogeneous
      data sources. We also briefly introduce the research in miRNA discovery and miRNA
      target identification with an emphasis on the challenges to computational
      biology. 

PMID- 23175683
TI  - Long-term results of treatments for functional single ventricle associated with
      extracardiac type total anomalous pulmonary venous connection.
AB  - OBJECTIVES: Surgical outcomes of patients with functional single ventricle have
      improved, though those for patients whose condition is complicated by
      extracardiac type total anomalous pulmonary venous connection (TAPVC) remain
      poor. We retrospectively reviewed our 21 years of surgical experiences with this
      challenging group. METHODS: From 1990 to 2010, 48 consecutive patients with
      functional single ventricle complicated by extracardiac TAPVC (26 males, 46 with
      right atrial isomerism) underwent initial surgical palliation at our centre. The
      median age and body weight at surgery were 69 days and 3.5 kg, respectively. The
      type of TAPVC was supracardiac in 31 patients, infracardiac in 14 and mixed type
      in 3. TAPVC was repaired in 25 patients before bidirectional Glenn (BDG) and 18
      at BDG, while it remained in 3 patients. Since 2007, stent implantation for
      obstructive drainage veins for patients with preoperative pulmonary venous
      obstruction and sutureless marsupialization for relief of postoperative pulmonary
      venous stenosis (PVS) have been initiated. The mean follow-up period was 4.2 +/-
      5.1 years. RESULTS: The overall survival rates at 1, 3 and 5 years after the
      initial surgical intervention were 58.3, 41.1 and 31.3%, respectively. Sixteen
      patients achieved the Fontan operation (33.3%). The freedom from postoperative
      PVS rates at 1 and 3 years after repair was 68.7 and 63.4%, respectively.
      Univariate analysis detected that infracardiac TAPVC (P = 0.036), coexisting
      major aortopulmonary collaterals (P = 0.017), and TAPVC repair before BDG (P =
      0.036) all reduced survival, and multivariable analysis indicated the repair of
      TAPVC before BDG as the only risk factor (P = 0.032). Whereas the occurrence of
      postoperative PVS did not reduce survival, which had a significant negative
      impact on achieving the Fontan operation (P = 0.008). The cumulative survival
      rate did not improve by surgical era. CONCLUSIONS: Surgical outcomes of patients
      with functional single ventricle undergoing the repair of extracardiac TAPVC in
      the neonatal period due to obstruction of the venous drainage pathway remain
      poor. Stent implantation for obstructive drainage veins to delay the timing of
      surgical correction and sutureless marsupialization as relief of postoperative
      PVS are expected to improve the late outcomes; however, the effect is still
      limited.

PMID- 23175684
TI  - An alternative approach to explantation and exchange of the HeartWare left
      ventricular assist device.
AB  - OBJECTIVES: Left ventricular assist device (LVAD) explantation and exchange is a
      relatively infrequent but potentially complex procedure. Patients requiring such
      procedures have multisystem suboptimal physiological reserve due to end-stage
      heart failure and are prone to complications. Less-invasive procedures are
      believed to facilitate postoperative recovery and early mobilization. We describe
      an alternative approach to explantation and exchange of the HeartWare LVAD
      through left thoracotomy. METHODS: Six patients (M = 4, F = 2, mean age = 49.16
      years) underwent device explant/exchange or initial implant (explant = 2,
      exchange = 3, initial implant = 1) through left thoracotomy utilizing
      cardiopulmonary bypass and induced ventricular fibrillation (VF). The mean bypass
      time and mean VF arrest time were 82 and 3 min, respectively. A new outflow graft
      was anastomosed to the previous outflow graft in 3 cases of device exchange and
      to the descending aorta in 1 case of initial implant. RESULTS: One patient died
      in the intensive care unit due to unrelated causes (gram-negative sepsis) after
      device exchange. All others were discharged alive and currently remain on follow
      up. The mean length of hospital stay was 40.66 days. CONCLUSIONS: On-pump
      approach through single thoracotomy incision is safe and equally suitable for
      device explant, exchange and initial implant. However, structural heart defects
      requiring surgical correction and the requirement of simultaneous right
      ventricular assist device are the limitations of this approach.

PMID- 23175685
TI  - Reply to Baisi et al.

PMID- 23175686
TI  - Model-based decision rules reduce the risk of molecular relapse after cessation
      of tyrosine kinase inhibitor therapy in chronic myeloid leukemia.
AB  - Molecular response to imatinib (IM) in chronic myeloid leukemia (CML) is
      associated with a biphasic but heterogeneous decline of BCR-ABL transcript
      levels. We analyzed this interindividual heterogeneity and provide a predictive
      mathematical model to prognosticate the long-term response and the individual
      risk of molecular relapse on treatment cessation. The parameters of the model
      were determined using 7-year follow-up data from a randomized clinical trial and
      validated by an independent dataset. Our model predicts that a subset of patients
      (14%) achieve complete leukemia eradication within less than 15 years and could
      therefore benefit from discontinuation of treatment. Furthermore, the model
      prognosticates that 31% of the patients will remain in deep molecular remission
      (MR(5.0)) after treatment cessation after a fixed period of 2 years in MR(5.0),
      whereas 69% are expected to relapse. As a major result, we propose a predictor
      that allows to assess the patient-specific risk of molecular relapse on treatment
      discontinuation and to identify patients for whom cessation of therapy would be
      an appropriate option. Application of the suggested rule for deciding about the
      time point of treatment cessation is predicted to result in a significant
      reduction in rate of molecular relapse.

PMID- 23175688
TI  - Clonal evolution and devolution after chemotherapy in adult acute myelogenous
      leukemia.
AB  - The frequent occurrence of persistent or relapsed disease after induction
      chemotherapy in AML necessitates a better understanding of the clonal
      relationship of AML in various disease phases. In this study, we used SNP 6.0
      array-based genomic profiling of acquired copy number aberrations (aCNA) and copy
      neutral LOH (cnLOH) together with sequence analysis of recurrently mutated genes
      to characterize paired AML genomes. We analyzed 28 AML sample pairs from patients
      who achieved complete remission with chemotherapy and subsequently relapsed and
      11 sample pairs from patients with persistent disease after induction
      chemotherapy. Through review of aCNA/cnLOH and gene mutation profiles in
      informative cases, we demonstrate that relapsed AML invariably represents re
      emergence or evolution of a founder clone. Furthermore, all individual aCNA or
      cnLOH detected at presentation persisted at relapse indicating that this lesion
      type is proximally involved in AML evolution. Analysis of informative paired
      persistent AML disease samples uncovered cases with 2 coexisting dominant clones
      of which at least one was chemotherapy sensitive and one resistant, respectively.
      These data support the conclusion that incomplete eradication of AML founder
      clones rather than stochastic emergence of fully unrelated novel clones underlies
      AML relapse and persistence with direct implications for clinical AML research.

PMID- 23175687
TI  - Inositol tetrakisphosphate limits NK cell effector functions by controlling PI3K
      signaling.
AB  - Natural killer (NK) cells have important functions in cancer immunosurveillance,
      BM allograft rejection, fighting infections, tissue homeostasis, and
      reproduction. NK cell-based therapies are promising treatments for blood cancers.
      Overcoming their currently limited efficacy requires a better understanding of
      the molecular mechanisms controlling NK cell development and dampening their
      effector functions. NK cells recognize the loss of self-antigens or up-regulation
      of stress-induced ligands on pathogen-infected or tumor cells through invariant
      NK cell receptors (NKRs), and then kill such stressed cells. Two second-messenger
      pathways downstream of NKRs are required for NK cell maturation and effector
      responses: PIP(3) generation by PI3K and generation of diacylglycerol and IP(3)
      by phospholipase-Cgamma (PLCgamma). In the present study, we identify a novel
      role for the phosphorylated IP(3) metabolite inositol (1,3,4,5)tetrakisphosphate
      (IP(4)) in NK cells. IP(4) promotes NK cell terminal differentiation and
      acquisition of a mature NKR repertoire. However, in mature NK cells, IP(4) limits
      NKR-induced IFNgamma secretion, granule exocytosis, and target-cell killing, in
      part by inhibiting the PIP(3) effector-kinase Akt. This identifies IP(4) as an
      important novel regulator of NK cell development and function and expands our
      understanding of the therapeutically important mechanisms dampening NK cell
      responses. Our results further suggest that PI3K regulation by soluble IP(4) is a
      broadly important signaling paradigm.

PMID- 23175689
TI  - Impaired thrombin-induced platelet activation and thrombus formation in mice
      lacking the Ca(2+)-dependent tyrosine kinase Pyk2.
AB  - In the present study, we used a knockout murine model to analyze the contribution
      of the Ca(2+)-dependent focal adhesion kinase Pyk2 in platelet activation and
      thrombus formation in vivo. We found that Pyk2-knockout mice had a tail bleeding
      time that was slightly increased compared with their wild-type littermates.
      Moreover, in an in vivo model of femoral artery thrombosis, the time to arterial
      occlusion was significantly prolonged in mice lacking Pyk2. Pyk2-deficient mice
      were also significantly protected from collagen plus epinephrine-induced
      pulmonary thromboembolism. Ex vivo aggregation of Pyk2-deficient platelets was
      normal on stimulation of glycoprotein VI, but was significantly reduced in
      response to PAR4-activating peptide, low doses of thrombin, or U46619. Defective
      platelet aggregation was accompanied by impaired inside-out activation of
      integrin alpha(IIb)beta(3) and fibrinogen binding. Granule secretion was only
      slightly reduced in the absence of Pyk2, whereas a marked inhibition of thrombin
      induced thromboxane A(2) production was observed, which was found to be
      responsible for the defective aggregation. Moreover, we have demonstrated that
      Pyk2 is implicated in the signaling pathway for cPLA(2) phosphorylation through
      p38 MAPK. The results of the present study show the importance of the focal
      adhesion kinase Pyk2 downstream of G-protein-coupled receptors in supporting
      platelet aggregation and thrombus formation.

PMID- 23175690
TI  - Cushing's syndrome after hemodialysis for 21 years.
AB  - CONTEXT: Hyperkalemia and weight loss are critical clinical problems for
      hemodialysis patients. There have been no documented reports of adrenal Cushing's
      syndrome with central obesity and hypokalemia in a hemodialysis patient.
      OBJECTIVE: The aim of the study was to report a patient with Cushing's syndrome
      after chronic hemodialysis, review the published literature, and discuss the
      significance of hypokalemia and obesity in anuric hemodialysis patients from the
      perspective of cortisol metabolism. PATIENT: A 61-yr-old woman who had been on
      hemodialysis for 21 yr presented with persistent hypokalemia and central obesity.
      In 2002, her dry weight was 48.1 kg, but thereafter she gained weight to 60 kg.
      RESULTS: Adrenal Cushing's syndrome was diagnosed from endocrinological findings
      such as increased cortisol secretion without a circadian rhythm and suppression
      of plasma ACTH. Spironolactone was administered (25 to 50 mg/d), and her serum
      potassium became normal. Then, left adrenalectomy was performed by laparoscopic
      surgery. The resected specimen contained a well-circumscribed adrenal adenoma
      expressing P450c17. After surgery, hypokalemia improved gradually without
      medication, and her weight gain stopped. CONCLUSIONS: This is the first
      documented case of adrenal Cushing's syndrome in a patient on long-term
      hemodialysis, although several authors have reported a relation between
      hypokalemia and primary hyperaldosteronism in hemodialysis patients.

PMID- 23175691
TI  - Metformin in obese children and adolescents: the MOCA trial.
AB  - CONTEXT: Childhood obesity is increasingly associated with type 2 diabetes (T2D).
      Metformin reduces the risk for T2D in adult obese nondiabetic patients, but the
      evidence in obese children and young people is inconclusive. OBJECTIVE: The
      objective of the study was to assess the effect of metformin on body mass index
      sd score (BMI-SDS), metabolic risk factors, and adipokines. DESIGN: This was a
      prospective, randomized, double-blind, placebo-controlled trial. SETTING: The
      study was conducted at six pediatric endocrine centers in the United Kingdom.
      PARTICIPANTS: One hundred fifty-one obese children and young people with
      hyperinsulinemia and/or impaired fasting glucose or impaired glucose tolerance
      (metformin: 74, placebo: 77). The study was comprised of 67.5% females, 65.6%
      postpubertal individuals, and 23.8% British Asian or Afro-Caribbean participants.
      The age range was 8-18 yr, the mean age was 13.7 (SD 2.3) yr, and the mean BMI
      SDS was +3.4 (SD 0.5). INTERVENTIONS: The intervention included metformin 1 g in
      the morning and 500 mg in the evening vs. placebo for 6 months. MAIN OUTCOME
      MEASURE: The main outcome measure was a reduction in BMI-SDS at 6 months.
      Secondary outcomes included insulin and glucose levels from oral glucose
      tolerance tests, alanine aminotransferase (ALT), and adiponectin to leptin ratio
      (ALR) at 3 and 6 months. RESULTS: Metformin was associated with a significant
      reduction in BMI-SDS compared with placebo at 6 months [mean difference -0.1 SD
      (95% confidence interval -0.18 to -0.02), P = 0.02]. Significant improvements at
      3 months were found in the metformin group: fasting glucose, -0.16 mmol/liter (
      0.31 to -0.00), P = 0.047; ALT, 19% (5-36%), P = 0.008; and ALR, 32% (4-67%), P =
      0.02. CONCLUSIONS: Metformin therapy has a beneficial treatment effect over
      placebo for BMI-SDS, fasting glucose, ALT, and ALR ratio at 3 months, with
      changes in BMI-SDS sustained at 6 months.

PMID- 23175692
TI  - Unique dominant negative mutation in the N-terminal mitochondrial targeting
      sequence of StAR, causing a variant form of congenital lipoid adrenal
      hyperplasia.
AB  - CONTEXT: Steroid acute regulatory (StAR) protein is a mitochondria-targeted
      protein that is part of the transduceosome complex crucial for transport of
      cholesterol to mitochondria. Recessive mutations cause classic and nonclassic
      congenital lipoid adrenal hyperplasia. OBJECTIVE: The aim of this study was to
      report the clinical, hormonal, genetic, and functional data of a novel
      heterozygous mutation in the StAR gene found in a 46,XY patient with ambiguous
      genitalia and neonatal severe steroidogenic deficiency. PATIENT: Undetectable
      serum steroids with high ACTH and plasma renin activity but normal acute GnRH
      response were found in infancy. After gonadectomy (at 3 yr of age), serum LH and
      testosterone were undetectable, whereas FSH was normal but increased slowly
      afterward. Estrogen replacement therapy, started at 10.2 yr of age, suppressed
      gonadotropins (for 2 yr). However, after 1 month off estrogens, the patient
      showed castrated levels. At 11.9 yr old, after fludrocortisone withdrawal because
      of hypertension, plasma renin activity and aldosterone remained normal,
      suggesting mineralocorticoid recovery by a StAR-independent mechanism. RESULTS:
      We found a de novo heterozygous IVS-2A>G StAR mutation and the reported
      heterozygous p.G146A SF1 polymorphism with normal CYP11A1, FDXR, FDX1, VDAC1, and
      TSPO genes. The mutant StAR transcript lacked exon 2, resulting in the in-frame
      loss of amino acids 22 to 59 in the N-terminal mitochondrial targeting signal. In
      vitro, the mutant protein exhibited reduced StAR activity in a dominant-negative
      manner and almost no mitochondria localization. CONCLUSIONS: A misfolded
      p.G22_L59del StAR might interfere with wild-type StAR activity by blocking the
      transduceosome complex, causing an autosomal dominant form of StAR deficiency,
      explaining the clinical phenotype. We speculated that estrogen might have
      modulated mineralocorticoid function and pubertal maturation in a human natural
      model lacking endogenous steroid production.

PMID- 23175693
TI  - Prevalence of germline TP53 mutations in a prospective series of unselected
      patients with adrenocortical carcinoma.
AB  - PURPOSE: Adrenocortical carcinoma (ACC) is a hallmark cancer in families with Li
      Fraumeni syndrome (LFS) caused by mutations in the TP53 gene. The prevalence of
      germline TP53 mutations in children diagnosed with ACC ranges from 50-97%.
      Although existing criteria advocate for TP53 testing in all patients with ACC
      regardless of age at diagnosis, the overall prevalence of germline mutations in
      patients diagnosed with ACC has not been well studied. PATIENTS AND METHODS: A
      total of 114 patients with confirmed ACC evaluated in the University of Michigan
      Endocrine Oncology Clinic were prospectively offered genetic counseling and TP53
      genetic testing, regardless of age at diagnosis or family history. Ninety-four of
      the 114 patients met with a genetic counselor (82.5%), with 53 of 94 (56.4%)
      completing TP53 testing; 9.6% (nine of 94) declined testing. The remainder (32 of
      94; 34%) expressed interest in testing but did not pursue it for various reasons.
      RESULTS: Four of 53 patients in this prospective, unselected series were found to
      have a TP53 mutation (7.5%). The prevalence of mutations in those diagnosed over
      age 18 was 5.8% (three of 52). There were insufficient data to estimate the
      prevalence in those diagnosed under age 18. None of these patients met clinical
      diagnostic criteria for classic LFS. Three of the families met criteria for Li
      Fraumeni-like syndrome; one patient met no existing clinical criteria for LFS or
      Li Fraumeni-like syndrome. Three of the four patients with mutations were
      diagnosed with ACC after age 45. CONCLUSIONS: Genetic counseling and germline
      testing for TP53 should be offered to all patients with ACC. Restriction on age
      at diagnosis or strength of the family history would fail to identify mutation
      carriers.

PMID- 23175694
TI  - Copy number variation on chromosome 10q26.3 for obesity identified by a genome
      wide study.
AB  - BACKGROUND: Obesity is a highly heritable disease defined by high body mass index
      (BMI). However, a large proportion of the heritability of obesity remains
      unexplained. Copy number variations (CNVs) might contribute to the missing
      heritability of obesity. METHODS: We conducted genome-wide CNV analyses on
      obesity phenotypes, including BMI and body fat mass in a discovery sample of 2215
      unrelated white subjects. After quality control, 314 CNVs were used for
      association tests. For significant CNVs identified, follow-up replication
      analyses were performed in three independent samples, including an unrelated
      sample of 1000 white subjects (OM sample), a family-based sample of 8385 white
      subjects (FHS sample), and an African-American sample of 1479 obesity cases and
      1575 lean controls (AA sample). RESULTS: Genome-wide CNV analyses detected that a
      CNV located at 10q26.3, which, even after multiple testing corrections, showed a
      strong association with both BMI (P = 2.30 * 10(-4), beta = 2.164) and body fat
      mass (P = 6.76 * 10(-5), beta = 4.126). This CNV was successfully replicated in
      the three replication samples (OM sample: P = 0.0465 for BMI, 0.0435 for fat
      mass; FHS sample: P = 0.0038 for BMI; AA sample: P = 0.0023 for obesity).
      Quantitative PCR validated this CNV, which covers a gene, CYP2E1. The protein
      encoded by CYP2E1 involves the synthesis of cholesterol, steroids and other
      lipids, which may have a potential impact on obesity. CONCLUSION: Our findings
      suggest the significant contribution of CNV10q26.3 to the pathogenesis of
      obesity.

PMID- 23175695
TI  - Cardiac magnetic resonance-derived anatomy, scar, and dyssynchrony fused with
      fluoroscopy to guide LV lead placement in cardiac resynchronization therapy: a
      comparison with acute haemodynamic measures and echocardiographic reverse
      remodelling.
AB  - AIMS: Left ventricular (LV) lead positioning for cardiac resynchronization
      therapy (CRT) is largely empirical and operator-dependent. Our aim was to
      determine whether cardiac magnetic resonance (CMR)-guided CRT may improve the
      acute and the chronic response. METHODS AND RESULTS: CMR-derived anatomical
      models and dyssynchrony maps were created for 20 patients. The CMR targets (three
      latest activated segments with <50% scar) were overlaid on to live fluoroscopy.
      Acute haemodynamic response (AHR) to LV pacing was assessed using an intra
      ventricular pressure wire. Chronic CRT response (end-systolic volume reduction
      >=15%) was assessed 6 months post-implantation. All patients underwent successful
      CMR-guided LV lead placement. A CMR target segment was paced in 75% of patients.
      The mean change in LVdP/dtmax for the CMR target was +14.2 +/- 12.5 vs. +18.7 +/-
      11.9% for the best AHR in any segment and +12.0 +/- 13.8% for the segment based
      on coronary sinus (CS) venography. Using CMR guidance, the acute responder rate
      was 60 vs. 50% on the basis of venography. At 6 months 60% of patients were
      echocardiographic responders. Of the echocardiographic responders, 92% were
      successfully paced in a CMR target segment compared with only 50% of non
      responders (P = 0.04). CONCLUSION: CMR guidance compared well when validated
      against the AHR. Lead placement was possible in the CMR target region in most
      patients with an AHR comparable with the best achieved in any CS branch. The
      chronic response was significantly better in patients paced in a CMR target
      segment. These results suggest that CMR guidance may represent a clinically
      useful tool for CRT.

PMID- 23175696
TI  - A simple yet effective chromogenic reagent for the rapid estimation of bromate
      and hypochlorite in drinking water.
AB  - We present a method for the rapid visible assay of bromate and hypochlorite in
      drinking water within 5 min. The assay utilizes a commercially common reagent and
      allows the determination of bromate and hypochlorite at several ppb levels with
      remarkably high selectivity over other ions.

PMID- 23175697
TI  - Modification of a tumor antigen determinant to improve peptide/MHC stability is
      associated with increased immunogenicity and cross-priming a larger fraction of
      CD8+ T cells.
AB  - Altered peptide ligands (APLs) with enhanced binding to MHC class I can increase
      the CD8(+) T cell response to native Ags, including tumor Ags. In this study, we
      investigate the influence of peptide-MHC (pMHC) stability on recruitment of tumor
      Ag-specific CD8(+) T cells through cross-priming. Among the four known H-2(b)
      restricted CD8(+) T cell determinants within SV40 large tumor Ag (TAg), the site
      V determinant ((489)QGINNLDNL(497)) forms relatively low-stability pMHC and is
      characteristically immunorecessive. Absence of detectable site V-specific CD8(+)
      T cells following immunization with wild-type TAg is due in part to inefficient
      cross-priming. We mutated nonanchor residues within the TAg site V determinant
      that increased pMHC stability but preserved recognition by both TCR-transgenic
      and polyclonal endogenous T cells. Using a novel approach to quantify the
      fraction of naive T cells triggered through cross-priming in vivo, we show that
      immunization with TAg variants expressing higher-stability determinants increased
      the fraction of site V-specific T cells cross-primed and effectively overcame the
      immunorecessive phenotype. In addition, using MHC class I tetramer-based
      enrichment, we demonstrate for the first time, to our knowledge, that endogenous
      site V-specific T cells are primed following wild-type TAg immunization despite
      their low initial frequency, but that the magnitude of T cell accumulation is
      enhanced following immunization with a site V variant TAg. Our results
      demonstrate that site V APLs cross-prime a higher fraction of available T cells,
      providing a potential mechanism for high-stability APLs to enhance immunogenicity
      and accumulation of T cells specific for the native determinant.

PMID- 23175698
TI  - Role of galectin-3 in classical and alternative macrophage activation in the
      liver following acetaminophen intoxication.
AB  - Inflammatory macrophages have been implicated in hepatotoxicity induced by the
      analgesic acetaminophen (APAP). In these studies, we characterized the phenotype
      of macrophages accumulating in the liver following APAP intoxication and
      evaluated the role of galectin-3 (Gal-3) in macrophage activation. Administration
      of APAP (300 mg/kg, i.p.) to wild-type mice resulted in the appearance of two
      distinct subpopulations of CD11b(+) cells in the liver, which expressed high or
      low levels of the monocyte/macrophage activation marker Ly6C. Whereas
      CD11b(+)/Ly6C(hi) macrophages exhibited a classically activated proinflammatory
      phenotype characterized by increased expression of TNF-alpha, inducible NO
      synthase, and CCR2, CD11b(+)/Ly6C(lo) macrophages were alternatively activated,
      expressing high levels of the anti-inflammatory cytokine IL-10. APAP intoxication
      was also associated with an accumulation of Gal-3(+) macrophages in the liver;
      the majority of these cells were Ly6C(hi). APAP-induced increases in
      CD11b(+)/Ly6C(hi) macrophages were significantly reduced in Gal-3(-/-) mice. This
      reduction was evident 72 h post APAP and was correlated with decreased expression
      of the classical macrophage activation markers, inducible NO synthase, IL-12, and
      TNF-alpha, as well as the proinflammatory chemokines CCL2 and CCL3, and chemokine
      receptors CCR1 and CCR2. Conversely, numbers of CD11b(+)/Ly6C(lo) macrophages
      increased in livers of APAP-treated Gal-3(-/-) mice; this was associated with
      increased expression of the alternative macrophage activation markers Ym1 and
      Fizz1, increased liver repair, and reduced hepatotoxicity. These data demonstrate
      that both classically and alternatively activated macrophages accumulate in the
      liver following APAP intoxication; moreover, Gal-3 plays a role in promoting a
      persistent proinflammatory macrophage phenotype.

PMID- 23175701
TI  - New strategies for the restoration of hearing loss: challenges and opportunities.
AB  - INTRODUCTION: For most types of hearing impairments, a definitive therapy would
      rest on the ability to restore hair cells and the spiral ganglion neurons. The
      only established technique to treat deafness is based on the functional
      replacement of hair cells with a cochlear implant, but this still has important
      limitations. SOURCES OF DATA: A systematic revision of the relevant literature is
      presented. AREAS OF AGREEMENT: New curative strategies, ranging from stem cells
      to gene and molecular therapy, are under development. AREAS OF CONTROVERSY:
      Although still experimental, they have delivered some initial promissory results
      that allow us to look at them with cautious optimism. GROWING POINTS: The
      isolation of human auditory cells, the generation of protocols to control their
      differentiation into sensory lineages, their promising application in vivo and
      the identification of key genes to target molecularly offer an exciting
      landscape. AREAS TIMELY FOR DEVELOPING RESEARCH: In this chapter, I discuss the
      latest advances in the field and how they are being translated into a clinical
      application.

PMID- 23175700
TI  - Anti-IFN-alpha/beta receptor antibody treatment ameliorates disease in lupus
      predisposed mice.
AB  - The demonstration in humans and mice that nucleic acid-sensing TLRs and type I
      IFNs are essential disease mediators is a milestone in delineating the mechanisms
      of lupus pathogenesis. In this study, we show that Ifnb gene deletion does not
      modify disease progression in NZB mice, thereby strongly implicating IFN-alpha
      subtypes as the principal pathogenic effectors. We further document that long
      term treatment of male BXSB mice with an anti-IFN-alpha/beta receptor Ab of mouse
      origin reduced serologic, cellular, and histologic disease manifestations and
      extended survival, suggesting that disease acceleration by the Tlr7 gene
      duplication in this model is mediated by type I IFN signaling. The efficacy of
      this treatment in BXSB mice was clearly evident when applied early in the disease
      process, but only partial reductions in some disease characteristics were
      observed when treatment was initiated at later stages. A transient therapeutic
      effect was also noted in the MRL-Fas(lpr) model, although overall mortality was
      unaffected. The combined findings suggest that IFN-alpha/beta receptor blockade,
      particularly when started at early disease stages, may be a useful treatment
      approach for human systemic lupus erythematosus and other autoimmune syndromes.

PMID- 23175702
TI  - Polydopamine-based molecular imprinting on silica-modified magnetic nanoparticles
      for recognition and separation of bovine hemoglobin.
AB  - Surface molecular imprinting, especially on the surface of silica-modified
      magnetic nanoparticles, has been proposed as a promising strategy for protein
      recognition and separation. Inspired by the self-polymerization of dopamine, we
      synthesized a polydopamine-based molecular imprinted film coating on silica
      Fe(3)O(4) nanoparticles for recognition and separation of bovine hemoglobin
      (BHb). Magnetic molecularly imprinted nanoparticles (about 860 nm) possess a core
      shell structure. Magnetic molecularly imprinted nanoparticles (MMIP) show a
      relatively high adsorption capacity (4.65 +/- 0.38 mg g(-1)) and excellent
      selectivity towards BHb with a separation factor of 2.19. MMIP with high
      saturation magnetization (10.33 emu g(-1)) makes it easy to separate the target
      protein from solution by an external magnetic field. After three continuous
      adsorption and elution processes, the adsorption capacity of MMIP remained at
      4.30 mg g(-1). Our results suggest that MMIPs are suitable for the removal of
      high abundance of protein and the enrichment of low abundance of protein in
      proteomics.

PMID- 23175704
TI  - A case of acute breathlessness in a swimmer.

PMID- 23175703
TI  - Acute abdomen in a young patient: the distant culprit.

PMID- 23175699
TI  - Molecular characterization of the early B cell response to pulmonary Cryptococcus
      neoformans infection.
AB  - The role of B cells in host defense against fungi has been difficult to
      establish. We quantified and determined the molecular derivation of B-1a, B-1b,
      and B-2 B cell populations in C57BL/6 mice after pulmonary infection with
      Cryptococcus neoformans. Total B-1 and B-2 cell numbers increased in lungs and
      peritoneal cavity as early as day 1 postinfection, but lacked signs of clonal
      expansion. Labeled capsular (24067) and acapsular (Cap67) C. neoformans strains
      were used to identify C. neoformans-binding B cell subsets by flow cytometry.
      Peritoneal cavity B-1a B cells exhibited the most acapsular and capsular C.
      neoformans binding in C. neoformans-infected mice, and C. neoformans-selected B-1
      B cells secreted laminarin- and C. neoformans-binding IgM. Single-cell PCR-based
      sequence analysis of B-1a, B-1b, and B-2 cell IgH V region H chain (V(H)) genes
      revealed increased usage of V(H)11 and V(H)12, respectively, in acapsular and
      capsular C. neoformans-selected B-1a cells. Germline V(H) segments were used,
      with capsular C. neoformans-selected cells having less junctional diversity than
      acapsular C. neoformans-selected cells. Further studies in B-1 B cell-depleted
      mice showed that these mice had higher brain and lung fungal burdens and less
      alveolar macrophage phagocytosis of C. neoformans than did control and B-1a B
      cell-reconstituted mice. Taken together, these results establish a mechanistic
      role for B-1 B cells in the innate B cell response to pulmonary infection with C.
      neoformans and reveal that IgM-producing B-1a cells, which express germline V(H)
      genes, bind C. neoformans and contribute to early fungal clearance. Thus, B-1a B
      cells provide a first line of defense during pulmonary C. neoformans infection in
      mice.

PMID- 23175705
TI  - The impact of adding clinical assistants on patient waiting time in a crowded
      emergency department.
AB  - BACKGROUND: Emergency department (ED) crowding causes prolonged waiting times.
      OBJECTIVE: To evaluate the potential benefit of introducing clinical assistants
      to a busy and crowded ED. METHODS: This was a retrospective cohort study at an
      urban, academic tertiary medical centre. We introduced one clinical assistant to
      each ED shift. The main task of clinical assistants was managing the flow of
      incoming ED patients. The case group consisted of all adult non-trauma emergency
      patients during the case period from 1 September to 30 November 2008. The first
      control group consisted of all adult non-trauma emergency patients between 1 June
      and 31 August 2008 and the second control group consisted of all patients treated
      between 1 September and 30 November 2007. The primary outcome was the 'waiting
      time', defined as the time from triage to the time of the first medical order
      entered into the computer system. The secondary outcome was the number of adult
      non-trauma emergency patients who left the ED without being seen. RESULTS: There
      were 12 257 cases and 25 950 controls. The mean and median waiting times were
      significantly shorter in the case group. The mean waiting time of the case group
      was 20.86 min, which was 4.51 min (17.8%) shorter than that of the first control
      group and 7.41 min (26.2%) shorter than that of the second control group. The
      median waiting time of the case group was also significantly shorter than those
      of the control groups. The number of the patients who left without being seen was
      significantly smaller in the case period. CONCLUSIONS: In a busy and crowded ED,
      the introduction of clinical assistants to an existing emergency health service
      effectively reduces patient waiting times and decreases the number of patients
      leaving without being seen.

PMID- 23175707
TI  - Treating epilepsy with a light potassium diet.
AB  - Gene therapy in a rat model of focal neocortical epilepsy decreases neuron
      excitability, preventing epileptogenesis and abrogating epileptic activity (Wykes
      et al.).

PMID- 23175709
TI  - Modulation of vigilance in the primary hypersomnias by endogenous enhancement of
      GABAA receptors.
AB  - The biology underlying excessive daytime sleepiness (hypersomnolence) is
      incompletely understood. After excluding known causes of sleepiness in 32
      hypersomnolent patients, we showed that, in the presence of 10 MUM gamma
      aminobutyric acid (GABA), cerebrospinal fluid (CSF) from these subjects
      stimulated GABA(A) receptor function in vitro by 84.0 +/- 40.7% (SD) relative to
      the 35.8 +/- 7.5% (SD) stimulation obtained with CSF from control subjects
      (Student's t test, t = 6.47, P < 0.0001); CSF alone had no effect on GABA(A)
      signaling. The bioactive CSF component had a mass of 500 to 3000 daltons and was
      neutralized by trypsin. Enhancement was greater for alpha2 subunit- versus alpha1
      subunit-containing GABA(A) receptors and negligible for alpha4 subunit-containing
      ones. CSF samples from hypersomnolent patients also modestly enhanced
      benzodiazepine (BZD)-insensitive GABA(A) receptors and did not competitively
      displace BZDs from human brain tissue. Flumazenil--a drug that is generally
      believed to antagonize the sedative-hypnotic actions of BZDs only at the
      classical BZD-binding domain in GABA(A) receptors and to lack intrinsic activity-
      nevertheless reversed enhancement of GABA(A) signaling by hypersomnolent CSF in
      vitro. Furthermore, flumazenil normalized vigilance in seven hypersomnolent
      patients. We conclude that a naturally occurring substance in CSF augments
      inhibitory GABA signaling, thus revealing a new pathophysiology associated with
      excessive daytime sleepiness.

PMID- 23175708
TI  - Mesenchymal stem cells regulate blood-brain barrier integrity through TIMP3
      release after traumatic brain injury.
AB  - Mesenchymal stem cells (MSCs) may be useful for treating a variety of disease
      states associated with vascular instability including traumatic brain injury
      (TBI). A soluble factor, tissue inhibitor of matrix metalloproteinase-3 (TIMP3),
      produced by MSCs is shown to recapitulate the beneficial effects of MSCs on
      endothelial function and to ameliorate the effects of a compromised blood-brain
      barrier (BBB) due to TBI. Intravenous administration of recombinant TIMP3
      inhibited BBB permeability caused by TBI, whereas attenuation of TIMP3 expression
      in intravenously administered MSCs blocked the beneficial effects of the MSCs on
      BBB permeability and stability. MSCs increased circulating concentrations of
      soluble TIMP3, which blocked vascular endothelial growth factor-A-induced
      breakdown of endothelial cell adherens junctions in vitro and in vivo. These
      findings elucidate a potential molecular mechanism for the beneficial effects of
      MSCs on the BBB after TBI and demonstrate a role for TIMP3 in the regulation of
      BBB integrity.

PMID- 23175711
TI  - Dealing with mental disorder in prisoners.

PMID- 23175712
TI  - Women "jurors" are asked how to present risk-benefit ratio of breast cancer
      screening.

PMID- 23175713
TI  - NHS spending should focus on mental rather than physical health to promote
      wellbeing.

PMID- 23175710
TI  - Activity of the calcium channel pore Cch1 is dependent on a modulatory region of
      the subunit Mid1 in Cryptococcus neoformans.
AB  - Calcium (Ca(2+))-mediated signaling events in fungal pathogens such as
      Cryptococcus neoformans are central to physiological processes, including those
      that mediate stress responses and promote virulence. The Cch1-Mid1 channel (CMC)
      represents the only high-affinity Ca(2+) channel in the plasma membrane of fungal
      cells; consequently, cryptococci cannot survive in low-Ca(2+) environments in the
      absence of CMC. Previous electrophysiological characterization revealed that
      Cch1, the predicted channel pore, and Mid1, a binding partner of Cch1, function
      as a store-operated Ca(2+)-selective channel gated by depletion of endoplasmic
      reticulum (ER) Ca(2+) stores. Cryptococci lacking CMC did not survive ER stress,
      indicating its critical role in restoring Ca(2+) homeostasis. Despite the
      requirement for Mid1 in promoting Ca(2+) influx via Cch1, identification of the
      role of Mid1 remains elusive. Here we show that the C-terminal tail of Mid1 is a
      modulatory region that impinges on Cch1 channel activity directly and mediates
      the trafficking of Mid1 to the plasma membrane. This region consists of the last
      24 residues of Mid1, and the functional expression of Mid1 in a human embryonic
      cell line (HEK293) and in C. neoformans is dependent on this domain.
      Substitutions of arginine (R619A) or cysteine (C621A) in the modulatory region
      failed to target Mid1 to the plasma membrane and prevented CMC activity.
      Interestingly, loss of a predicted protein kinase C (PKC)-phosphorylated serine
      residue (S605A) had no effect on Mid1 trafficking but did alter the kinetics of
      Cch1 channel activity. Thus, establishment of Ca(2+) homeostasis in C. neoformans
      is dependent on a modulatory domain of Mid1.

PMID- 23175714
TI  - Commissioners must "dismantle existing NHS services as they see fit," doctors'
      leader says.

PMID- 23175715
TI  - Slow DNA loss in the gigantic genomes of salamanders.
AB  - Evolutionary changes in genome size result from the combined effects of mutation,
      natural selection, and genetic drift. Insertion and deletion mutations (indels)
      directly impact genome size by adding or removing sequences. Most species lose
      more DNA through small indels (i.e., ~1-30 bp) than they gain, which can result
      in genome reduction over time. Because this rate of DNA loss varies across
      species, small indel dynamics have been suggested to contribute to genome size
      evolution. Species with extremely large genomes provide interesting test cases
      for exploring the link between small indels and genome size; however, most large
      genomes remain relatively unexplored. Here, we examine rates of DNA loss in the
      tetrapods with the largest genomes-the salamanders. We used low-coverage genomic
      shotgun sequence data from four salamander species to examine patterns of
      insertion, deletion, and substitution in neutrally evolving non-long terminal
      repeat (LTR) retrotransposon sequences. For comparison, we estimated genome-wide
      DNA loss rates in non-LTR retrotransposon sequences from five other vertebrate
      genomes: Anolis carolinensis, Danio rerio, Gallus gallus, Homo sapiens, and
      Xenopus tropicalis. Our results show that salamanders have significantly lower
      rates of DNA loss than do other vertebrates. More specifically, salamanders
      experience lower numbers of deletions relative to insertions, and both deletions
      and insertions are skewed toward smaller sizes. On the basis of these patterns,
      we conclude that slow DNA loss contributes to genomic gigantism in salamanders.
      We also identify candidate molecular mechanisms underlying these differences and
      suggest that natural variation in indel dynamics provides a unique opportunity to
      study the basis of genome stability.

PMID- 23175717
TI  - NHS chief is forbidden from lobbying health department for two years after moving
      to private sector.

PMID- 23175716
TI  - Insect phylogenomics: exploring the source of incongruence using new
      transcriptomic data.
AB  - The evolution of the diverse insect lineages is one of the most fascinating
      issues in evolutionary biology. Despite extensive research in this area, the
      resolution of insect phylogeny especially of interordinal relationships has
      turned out to be still a great challenge. One of the challenges for insect
      systematics is the radiation of the polyneopteran lineages with several
      contradictory and/or unresolved relationships. Here, we provide the first
      transcriptomic data for three enigmatic polyneopteran orders (Dermaptera,
      Plecoptera, and Zoraptera) to clarify one of the most debated issues among higher
      insect systematics. We applied different approaches to generate 3 data sets
      comprising 78 species and 1,579 clusters of orthologous genes. Using these three
      matrices, we explored several key mechanistic problems of phylogenetic
      reconstruction including missing data, matrix selection, gene and taxa
      number/choice, and the biological function of the genes. Based on the first
      phylogenomic approach including these three ambiguous polyneopteran orders, we
      provide here conclusive support for monophyletic Polyneoptera, contesting the
      hypothesis of Zoraptera + Paraneoptera and Plecoptera + remaining Neoptera. In
      addition, we employ various approaches to evaluate data quality and highlight
      problematic nodes within the Insect Tree that still exist despite our
      phylogenomic approach. We further show how the support for these nodes or
      alternative hypotheses might depend on the taxon- and/or gene-sampling.

PMID- 23175718
TI  - GPs' pleas for their conflict of interests to be treated with leniency are
      rejected by commissioning board.

PMID- 23175719
TI  - MPs are to investigate need for drug companies to share clinical trial data.

PMID- 23175720
TI  - High job vacancy rates in hospitals and nursing homes underpin poor care, says
      watchdog.

PMID- 23175721
TI  - Risk factors for intracerebral hemorrhage differ according to hemorrhage
      location.
AB  - OBJECTIVES: Risk factors have been described for spontaneous intracerebral
      hemorrhage (ICH); their relative contribution to lobar vs nonlobar hemorrhage
      location is less clear. Our purpose here was to investigate risk factors by
      hemorrhage location. METHODS: This case-control study prospectively enrolled
      subjects with first-ever spontaneous ICH and matched each with up to 3 controls
      by age, race, and gender. Conditional stepwise logistic regression modeling was
      used to determine significant independent risk factors for lobar and nonlobar
      ICH. RESULTS: From December 1997 through December 2006, 597 cases and 1,548
      controls qualified for the analysis. Hypertension, warfarin use, first-degree
      relative with ICH, personal history of ischemic stroke, less than a high school
      education, and APOE epsilon2 or epsilon4 genotype were more common in ICH cases.
      Hypercholesterolemia and moderate alcohol consumption (<= 2 drinks per day) were
      less common in ICH cases. The associations of hypertension and
      hypercholesterolemia were specific for nonlobar ICH. Conversely, the association
      of APOE epsilon2 or epsilon4 genotype was specific for lobar ICH. CONCLUSIONS:
      APOE epsilon2 or epsilon4 genotype was associated specifically with lobar ICH.
      Hypertension was associated specifically with nonlobar ICH. A protective
      association was seen between hypercholesterolemia and nonlobar ICH; no such
      association was identified for lobar ICH.

PMID- 23175722
TI  - Impairment of JCV-specific T-cell response by corticotherapy: effect on PML-IRIS
      management?
AB  - OBJECTIVE: To investigate the impact of corticosteroids (CS) on the viral
      specific T-cell response, in particular the JC virus (JCV)-specific one, in an
      attempt to determine the optimal timing of CS in the management of progressive
      multifocal leukoencephalopathy-immune reconstitution inflammatory syndrome (PML
      IRIS). METHODS: A blood draw was performed before and 7 days after the
      administration of IV CS to 24 patients with relapsing multiple sclerosis (MS).
      The phenotypic pattern of T cells was determined by CCR7 and CD45RA. To assess
      the impact of CS treatment on proliferative response of JCV-, influenza-, and
      Epstein-Barr virus (EBV)-specific T cells, a thymidine incorporation
      proliferation assay was performed. An intracellular cytokine staining assay was
      performed to determine the effect of CS treatment on the production of cytokine
      by virus-specific T cells. JCV T-cell assays were performed only in JCV-infected
      patients with MS as detected by serologies (Stratify) or detection of JCV DNA in
      the urine by PCR. RESULTS: CS led T cells, CD4+ and CD8+, toward a less
      differentiated phenotype. There was a significant decrease of EBV-, influenza-,
      and JCV-specific T-cell proliferative response upon CS treatment. There was a
      significant decrease in the frequency of interferon (IFN) gamma- and tumor
      necrosis factor (TNF) alpha-producing JCV-specific CD8+ T cells, but not EBV- or
      influenza-specific CD4+ or CD8+ T cells. CONCLUSIONS: CS have a profound impact
      on the virus-specific T-cell response, especially on JCV, suggesting that when CS
      are considered, they should not be given before the onset of clinical or
      radiologic signs of IRIS. Studies addressing directly patients with MS with
      natalizumab-caused PML are warranted. CLASSIFICATION OF EVIDENCE: This study
      provides Class III evidence that methylprednisolone treatment decreases the
      frequency of JCV-specific CD8+ T cells producing IFN-gamma and TNFalpha,
      impairing control of JCV, suggesting this should be used to treat but not to
      prevent PML-IRIS. No clinical outcomes were measured.

PMID- 23175724
TI  - Serial proton magnetic resonance spectroscopy of normal-appearing gray and white
      matter in MS.

PMID- 23175723
TI  - Stroke Prognostication using Age and NIH Stroke Scale: SPAN-100.
AB  - OBJECTIVES: Age and stroke severity are major determinants of stroke outcomes,
      but systematically incorporating these prognosticators in the routine practice of
      acute ischemic stroke can be challenging. We evaluated the effect of an index
      combining age and stroke severity on response to IV tissue plasminogen activator
      (tPA) among patients in the National Institute of Neurological Disorders and
      Stroke (NINDS) tPA stroke trials. METHODS: We created the Stroke Prognostication
      using Age and NIH Stroke Scale (SPAN) index by combining age in years plus NIH
      Stroke Scale (NIHSS) >=100. We applied the SPAN-100 index to patients in the
      NINDS tPA stroke trials (parts I and II) to evaluate its ability to predict
      clinical response and risk of intracerebral hemorrhage (ICH) after thrombolysis.
      The main outcome measures included ICH (any type) and a composite favorable
      outcome (defined as a modified Rankin Scale score of 0 or 1, NIHSS <=1, Barthel
      index >=95, and Glasgow Outcome Scale score of 1) at 3 months. Bivariate and
      multivariable logistic regression analyses were used to determine the association
      between SPAN-100 and outcomes of interest. RESULTS: Among 624 patients in the
      NINDS trials, 62 (9.9%) participants were SPAN-100 positive. Among those
      receiving tPA, ICH rates were higher for SPAN-100-positive patients (42% vs 12%
      in SPAN-100-negative patients; p < 0.001); similarly, ICH rates were higher in
      SPAN-100-positive patients (19% vs 5%; p = 0.005) among those not receiving tPA.
      SPAN-100 was associated with worse outcomes. The benefit of tPA, defined as
      favorable composite outcome at 3 months, was present in SPAN-100-negative
      patients (55.4% vs 40.2%; p < 0.001), but not in SPAN-100-positive patients (5.6%
      tPA vs 3.9%; p = 0.76). Similar trends were found for secondary outcomes (e.g.,
      symptomatic ICH, catastrophic outcome, discharge home). CONCLUSION: The SPAN-100
      index could be a simple method for estimating the clinical response and risk of
      hemorrhagic complications after tPA for acute ischemic stroke. These results need
      further confirmation in larger contemporary datasets.

PMID- 23175725
TI  - Comment: avoiding detrimental effects of corticosteroids on JC virus T-cell
      responses--primum non nocere.

PMID- 23175726
TI  - Temporal association tracts and the breakdown of episodic memory in mild
      cognitive impairment.
AB  - OBJECTIVE: To examine the pattern of association between microstructure of
      temporal lobe connections and the breakdown of episodic memory that is a core
      feature of mild cognitive impairment (MCI). METHODS: Twenty-five individuals with
      MCI and 20 matched controls underwent diffusion MRI and cognitive assessment.
      Three temporal pathways were reconstructed by tractography: fornix,
      parahippocampal cingulum (PHC), and uncinate fasciculus. Tissue volume fraction-a
      tract-specific measure of atrophy-and microstructural measures were derived for
      each tract. To test specificity of associations, a comparison tract
      (corticospinal tract) and control cognitive domains were also examined. RESULTS:
      In MCI, tissue volume fraction was reduced in the fornix. Axial and radial
      diffusivity were increased in uncinate and PHC implying more subtle
      microstructural change. In controls, tissue volume fraction in the fornix was the
      predominant correlate of free recall. In contrast, in MCI, the strongest
      relationship was with left PHC. Microstructure of uncinate and PHC also
      correlated with recognition memory, and recognition confidence, in MCI.
      CONCLUSIONS: Episodic memory in MCI is related to the structure of multiple
      temporal association pathways. These associations are not confined to the fornix,
      as they are in healthy young and older adults. In MCI, because of a compromised
      fornix, alternative pathways may contribute disproportionally to episodic memory
      performance.

PMID- 23175728
TI  - Prediction of outcome after ischemic stroke: the value of clinical scores.

PMID- 23175727
TI  - Depression in epilepsy: a systematic review and meta-analysis.
AB  - OBJECTIVE: To estimate the prevalence of depression in persons with epilepsy
      (PWE) and the strength of association between these 2 conditions. METHODS: The
      MEDLINE (1948-2012), EMBASE (1980-2012), and PsycINFO (1806-2012) databases,
      reference lists of retrieved articles, and conference abstracts were searched.
      Content experts were also consulted. Two independent reviewers screened abstracts
      and extracted data. For inclusion, studies were population-based, original
      research, and reported on epilepsy and depression. Estimates of depression
      prevalence among PWE and of the association between epilepsy and depression
      (estimated with reported odds ratios [ORs]) are provided. RESULTS: Of 7,106
      abstracts screened, 23 articles reported on 14 unique data sources. Nine studies
      reported on 29,891 PWE who had an overall prevalence of active (current or past
      year) depression of 23.1% (95% confidence interval [CI] 20.6%-28.31%). Five of
      the 14 studies reported on 1,217,024 participants with an overall OR of active
      depression of 2.77 (95% CI 2.09-3.67) in PWE. For lifetime depression, 4 studies
      reported on 5,454 PWE, with an overall prevalence of 13.0% (95% CI 5.1-33.1), and
      3 studies reported on 4,195 participants with an overall OR of 2.20 (95% CI 1.07
      4.51) for PWE. CONCLUSIONS: Epilepsy was significantly associated with depression
      and depression was observed to be highly prevalent in PWE. These findings
      highlight the importance of proper identification and management of depression in
      PWE.

PMID- 23175729
TI  - The border-land of epilepsy--revisited.

PMID- 23175730
TI  - Intrinsic epileptogenicity of cortical tubers revealed by intracranial EEG
      monitoring.
AB  - OBJECTIVE: We sought to identify intracranial EEG patterns characteristic of
      epileptogenic tubers and to understand the contribution of perituberal cortex.
      METHODS: Twenty-three intracranial EEG monitoring studies were reviewed from 17
      children aged 1.3-7.7 years with tuberous sclerosis complex and intractable
      multifocal epilepsy, 14 with a history of epileptic spasms. Interictal
      epileptiform discharges and ictal rhythms for 60 electroclinically distinct
      seizures (EDS) were analyzed in relation to 162 sampled tubers. RESULTS:
      Localized, tuber-related, ictal rhythms were seen in 49/60 EDS, most commonly as
      low-voltage fast activity recruiting to rhythmic spiking, then diffuse slowing or
      bursts of ripple range activity. Ictal onset in localized EDS involved only
      tubers in 57% and tubers with perituberal cortex in 31%. Ictal fast ripples (FR)
      noted at seizure onset in 15/38 localized EDS were confined to tubers in 73% and
      involved tuber with perituberal cortex in 27%. Intraictal activation occurred
      during seizure propagation in 19 localized EDS, being to tubers in 63% and to
      tubers with perituberal cortex in 37%; 63% of activated tubers generated
      independent EDS. Trains of periodic sharp waves on an attenuated background were
      seen interictally at 36/162 tubers, with 67% of those tubers generating EDS (p =
      0.0001). Interictal FR, when present, involved tubers more commonly than
      perituberal cortex but were not associated with EDS. CONCLUSION: The study
      demonstrates interictal and ictal intracranial EEG findings characteristic of
      epileptogenic tubers, suggests that tubers play a greater role in seizure genesis
      than perituberal cortex, and suggests tuberectomy may be a sufficient surgical
      approach in a number of patients.

PMID- 23175731
TI  - A novel hereditary extensive vascular leukoencephalopathy mapping to chromosome
      20q13.
AB  - OBJECTIVE: The detection of a leukoencephalopathy is a frequent situation in
      neurologic practice. In a number of cases, the etiology remains obscure despite
      extensive investigations. We characterized the clinical, pathologic, and genetic
      features of a novel hereditary vascular leukoencephalopathy. METHODS: After the
      observation of a similar leukoencephalopathy in 2 sisters, clinical,
      neuroimaging, and molecular genetics investigations were conducted in 21 of their
      consenting relatives. Pathologic data were obtained in one patient. RESULTS:
      Fourteen members presented with significant white matter lesions at MRI
      examination, among whom only 5 individuals were symptomatic. The main clinical
      manifestations included gait disturbances, transient movement disorders, stroke,
      and cognitive dysfunction. The 9 remaining members aged from 26 to 60 years were
      asymptomatic. The MRI pattern was highly stereotyped with symmetric white matter
      hyperintensities worsening with patient's age. We mapped the gene involved in
      this condition on chromosome 20q13. Neuropathologic examination suggested that
      this leukoencephalopathy is underlaid by a cerebral arteriolopathy affecting
      small preterminal arterioles, clearly distinct from amyloid angiopathy and
      hypertension-related small-vessel disease. CONCLUSIONS: These data establish that
      this family is affected by a novel autosomal dominant vascular
      leukoencephalopathy mapping to chromosome 20q13. This disease is characterized by
      a progressive and age-related hemispheric and brainstem leukoencephalopathy
      contrasting with the paucity and late onset of clinical symptoms in most of the
      cases.

PMID- 23175733
TI  - Myopathy with lobulated fibers, cores, and rods caused by a mutation in collagen
      VI.

PMID- 23175732
TI  - Serial proton MR spectroscopy of gray and white matter in relapsing-remitting MS.
AB  - OBJECTIVE: To characterize and follow the diffuse gray and white matter (GM/WM)
      metabolic abnormalities in early relapsing-remitting multiple sclerosis using
      proton magnetic resonance spectroscopic imaging ((1)H-MRSI). METHODS: Eighteen
      recently diagnosed, mildly disabled patients (mean baseline time from diagnosis
      32 months, mean Expanded Disability Status Scale [EDSS] score 1.3), all on
      immunomodulatory medication, were scanned semiannually for 3 years with T1
      weighted and T2-weighted MRI and 3D (1)H-MRSI at 3 T. Ten sex- and age-matched
      controls were followed annually. Global absolute concentrations of N
      acetylaspartate (NAA), choline (Cho), creatine (Cr), and myo-inositol (mI) were
      obtained for all GM and WM in the 360 cm(3) (1)H-MRSI volume of interest.
      RESULTS: Patients' average WM Cr, Cho, and mI concentrations (over all time
      points), 5.3 +/- 0.4, 1.6 +/- 0.1, and 5.1 +/- 0.7 mM, were 8%, 12%, and 11%
      higher than controls' (p <= 0.01), while their WM NAA, 7.4 +/- 0.7 mM, was 6%
      lower (p = 0.07). There were increases with time of patients' WM Cr: 0.1 mM/year,
      Cho: 0.02 mM/year, and NAA: 0.1 mM/year (all p < 0.05). None of the patients'
      metabolic concentrations correlated with their EDSS score, relapse rate,
      GM/WM/CSF fractions, or lesion volume. CONCLUSIONS: Diffuse WM glial
      abnormalities were larger in magnitude than the axonal abnormalities and
      increased over time independently of conventional clinical or imaging metrics and
      despite immunomodulatory treatment. In contrast, the axonal abnormalities showed
      partial recovery, suggesting that patients' lower WM NAA levels represented a
      dysfunction, which may abate with treatment. Absence of detectable diffuse
      changes in GM suggests that injury there is minimal, focal, or heterogeneous
      between cortex and deep GM nuclei.

PMID- 23175734
TI  - Electric shocks at work in Europe: development of a job exposure matrix.
AB  - OBJECTIVES: Electric shocks have been suggested as a potential risk factor for
      neurological disease, in particular for amyotrophic lateral sclerosis. While
      actual exposure to shocks is difficult to measure, occurrence and variation of
      electric injuries could serve as an exposure proxy. We assessed risk of electric
      injury, using occupational accident registries across Europe to develop an
      electric shock job-exposure-matrix (JEM). MATERIALS AND METHODS: Injury data were
      obtained from five European countries, and the number of workers per occupation
      and country from EUROSTAT was compiled at a 3-digit International Standard
      Classification of Occupations 1988 level. We pooled accident rates across
      countries with a random effects model and categorised jobs into low, medium and
      high risk based on the 75th and 90th percentile. We next compared our JEM to a
      JEM that classified extremely low frequency magnetic field exposure of jobs into
      low, medium and high. RESULTS: Of 116 job codes, occupations with high potential
      for electric injury exposure were electrical and electronic equipment mechanics
      and fitters, building frame workers and finishers, machinery mechanics and
      fitters, metal moulders and welders, assemblers, mining and construction
      labourers, metal-products machine operators, ships' decks crews and power
      production and related plant operators. Agreement between the electrical injury
      and magnetic field JEM was 67.2%. CONCLUSIONS: Our JEM classifies occupational
      titles according to risk of electric injury as a proxy for occurrence of electric
      shocks. In addition to assessing risk potentially arising from electric shocks,
      this JEM might contribute to disentangling risks from electric injury from those
      of extremely low frequency magnetic field exposure.

PMID- 23175735
TI  - A randomised controlled trial of hospital-based case management to improve
      colorectal cancer patients' health-related quality of life and evaluations of
      care.
AB  - OBJECTIVE: To analyse the effectiveness of hospital-based case management (CM) in
      terms of patient-reported outcomes. DESIGN: Randomised controlled trial
      allocating participants 1 : 1 to either a CM intervention or a control group.
      Allocation status was evident to participants and case managers, but blinded to
      researchers. SETTING: Patients were recruited at a Danish surgical department
      where the case managers were situated. PARTICIPANTS: Colorectal cancer patients
      who were to undergo further investigation or treatment. Exclusion criteria were
      participation in another study, poor Danish language skills or apparent cognitive
      impairment. 140 participants were randomised to each group. Recruitment period
      was 11 March 2009 to 29 December 2010. INTERVENTIONS: Control group patients had
      usual care. Intervention group patients had usual care supplemented by hospital
      based CM started at first visit to the out-patient clinic (before treatment
      start) and ended 4 weeks after completed cancer treatment. CM was conducted by
      nurse case managers who undertook care pathway supervision, information
      dissemination to health professionals and outreaching patient support. OUTCOME
      MEASURES: Patient-reported global quality of life measured with the EORTC QLQ-C30
      and eight ad hoc, piloted patient evaluation items assessed at eight, 30 and 52
      weeks after randomisation. RESULTS: The two groups were comparable as to
      questionnaire response rates and completed scales/items. There were no
      statistically significant group differences on any of the health-related quality
      of life subscales at eight, 30 or 52 weeks. In patient evaluations, all point
      estimates favoured CM at week 8 and 30; at week 52, 6 of 7 estimates favoured CM.
      CONCLUSIONS: We found no evidence that CM influenced colorectal cancer patients'
      health-related quality of life. Patients allocated to CM evaluated their care
      more positively than patients receiving usual care. TRIAL REGISTRATION:
      Clinicaltrials.gov identifier: NCT00845247.

PMID- 23175736
TI  - Descriptive analysis of the respiratory health status of persons exposed to Libby
      amphibole asbestos.
AB  - OBJECTIVE: Describe respiratory health and quality of life in persons exposed to
      Libby amphibole asbestos (LAA) contaminated vermiculite. DESIGN: Cross-sectional
      descriptive. SETTING: Asbestos-related disease clinic in Libby, Montana USA.
      PARTICIPANTS: 329 individuals exposed to LAA; mostly men, married, between 50 and
      69 years; two-thirds lived in the surrounding county; one-third lived elsewhere
      in the state and USA. PRIMARY OUTCOME MEASURES: Chest radiograph (CXR), pulmonary
      function data and the St George Respiratory Questionnaire (SGRQ). RESULTS:
      Exposure categories included vermiculite workers=7.6%; family/household contact
      of vermiculite worker=32%; and environmental exposure only=60%. Of the
      participants, 55% had only pleural abnormalities; 5.4% had only interstitial
      abnormalities; nearly 21% had both abnormalities and 18% had no lung abnormality
      on chest x-ray. Mean forced vital capacity (FVC) 95.3% (SD=18.7); forced
      expiratory volume (FEV(1)) mean 87% (SD=20.2); ratio of FEV1(1)/FVC 95.5%
      (SD=12.0); and diffusing capacity (DLCO) of 83% (SD=21.7) of the percent
      predicted. The mean total SGRQ (38.5; SD=22.1) indicated a lower quality of life
      than healthy persons and persons with other chronic conditions. SGRQ subscale
      means were Symptoms 52.1 (SD=24.9), activity 49.4 (SD=26.9) and impacts 27.5
      (SD=21.9). Participants with normal CXR differed significantly from those with
      both interstitial and pleural abnormalities on total, activity and impacts
      scores. For activity alone, subjects with normal CXR differed significantly from
      those with pleural disease; no differences were found for those with interstitial
      disease. Significant findings were found for smoking history across all pulmonary
      measures, and for exposure status, radiographic findings, age and gender for
      select pulmonary parameters. Subjects with any smoking history had significantly
      worse average total and subscale scores on the SGRQ. CONCLUSIONS: Of 329 persons
      exposed to LAA, the majority (182) had pleural abnormalities identified on CXR.
      SGRQ scores for persons with abnormalities (pleural, interstitial or both) (269)
      differed significantly from those with a normal CXR.

PMID- 23175737
TI  - Missed opportunities: childhood learning disabilities as early indicators of risk
      among homeless adults with mental illness in Vancouver, British Columbia.
AB  - OBJECTIVES: It is well documented that early-learning problems and poor academic
      achievement adversely impact child development and a wide range of adult
      outcomes; however, these indicators have received scant attention among homeless
      adults. This study examines self-reported learning disabilities (LD) in childhood
      as predictors of duration of homelessness, mental and substance use disorders,
      physical health, and service utilisation in a sample of homeless adults with
      current mental illness. DESIGN: This study was conducted using the baseline
      sample from a randomised controlled trial (RCT). SETTING: Participants were
      sampled from the community in Vancouver, British Columbia. PARTICIPANTS: The
      total sample included 497 adult participants who met criteria for absolute
      homelessness or precarious housing and a current mental disorder based on a
      structured diagnostic interview. Learning disabilities in childhood were assessed
      by asking adult participants whether they thought they had an LD in childhood and
      if anyone had told them they had an LD. Only participants who responded
      positively to both questions (n=133) were included in the analyses. OUTCOME
      MEASURES: Primary outcomes include current mental disorders, substance use
      disorders, physical health, service utilisation and duration of homelessness.
      RESULTS: In multivariable regression models, self-reported LD during childhood
      independently predicted self-reported educational attainment and lifetime
      duration of homelessness as well as a range of mental health, physical health and
      substance use problems, but did not predict reported health or justice service
      utilisation. CONCLUSIONS: Childhood learning problems are overrepresented among
      homeless adults with complex comorbidities and long histories of homelessness.
      Our findings are consistent with a growing body of literature indicating that
      adverse childhood events are potent risk factors for a number of adult health and
      psychiatric problems, including substance abuse.   TRIALS REGISTRATION NUMBER: 
      This trial has been registered with the International Standard Randomised Control
      Trial Number Register and assigned ISRCTN42520374.

PMID- 23175738
TI  - A randomised clinical trial of comprehensive cardiac rehabilitation versus usual
      care for patients treated for infective endocarditis--the CopenHeartIE trial
      protocol.
AB  - INTRODUCTION: Infective endocarditis (IE) is among the most serious infectious
      diseases in the western world. Treatment requires lengthy hospitalisation, high
      dosage antibiotic therapy and possible valve replacement surgery. Despite
      advances in treatment, the 1-year mortality remains at 20-40%. Studies indicate
      that patients experience persisting physical symptoms, diminished quality of life
      and difficulties returning to work up to a year postdischarge. No studies
      investigating the effects of rehabilitation have been published. We present the
      rationale and design of the CopenHeart(IE) trial, which investigates the effect
      of comprehensive cardiac rehabilitation versus usual care for patients treated
      for IE. METHODS AND ANALYSIS: We will conduct a randomised clinical trial to
      investigate the effects of comprehensive cardiac rehabilitation versus usual care
      on the physical and psychosocial functioning of patients treated for IE. The
      trial is a multicentre, parallel design trial with 1 : 1 individual randomisation
      to either the intervention or control group. The intervention consists of five
      psychoeducational consultations provided by specialised nurses and a 12-week
      exercise training programme. The primary outcome is mental health (MH) measured
      by the standardised Short Form 36 (SF-36). The secondary outcome is peak oxygen
      uptake measured by the bicycle ergospirometry test. Furthermore, a number of
      exploratory analyses will be performed. Based on sample size calculation, 150
      patients treated for left-sided (native or prosthetic valve) or cardiac device
      endocarditis will be included in the trial. A qualitative and a survey-based
      complementary study will be undertaken, to investigate postdischarge experiences
      of the patients. A qualitative postintervention study will explore rehabilitation
      participation experiences. ETHICS AND DISSEMINATION: The study complies with the
      Declaration of Helsinki and was approved by the regional research ethics
      committee (no H-1-2011-129) and the Danish Data Protection Agency (no 2007-58
      0015). Study findings will be disseminated widely through peer-reviewed
      publications and conference presentations. REGISTRATION: Clinicaltrials.gov
      identifier: NCT01512615.

PMID- 23175739
TI  - Effects of enzyme replacement therapy in adult patients with Fabry disease on
      cardiac structure and function: a retrospective cohort study of the Fabry Munster
      Study (FaMuS) data.
AB  - OBJECTIVE: Fabry disease (FD) is an X-linked inborn error of glycosphingolipid
      catabolism caused by deficient lysosomal alpha-galactosidase A activity.
      Progressive accumulation of globotriaosylceramide and related glycosphingolipids
      in vascular endothelial lysosomes of the heart, kidneys and brain is responsible
      for the main disease manifestations. The aim of our study was to assess short
      term and long-term effects of enzyme replacement therapy (ERT) on cardiac mass
      and function. DESIGN: Retrospective cohort study. SETTING: Hospital outpatient
      clinic. PARTICIPANTS: 40 FD patients (21 men, 19 women) receiving agalsidase beta
      ERT. OUTCOME MEASURES: The focus at baseline and follow-up examinations was on
      structural, functional (Doppler-echocardiography) as well as electrical changes
      (ECG) and blood pressure. RESULTS: In the Early Group, systolic and diastolic
      blood pressures significantly decreased. Left-ventricular (LV) also decreased;
      however, wall thickness and LV mass index showed no further increase. VE as an
      indicator for diastolic function significantly improved (64+/-21 vs 75+/-27 cm/s,
      p=0.038). There were no significant changes of ECG parameters. There were few
      relevant changes in the Late Group, albeit systolic blood pressure significantly
      decreased and QRS duration significantly increased. In conclusion,
      echocardiographic left-ventricular mass index, interventricular septum thickness,
      left-ventricular posterior wall, left-ventricular end-diastolic dimension) and
      diastolic function parameters are valuable for follow-up and guidance of therapy.
      CONCLUSIONS: The primary positive impact of ERT appears to be an early effect
      after the start of therapy, and early initiation of ERT should be recommended.

PMID- 23175740
TI  - Timing of gastrostomy insertion in children with a neurodisability: a cross
      sectional study of early versus late intervention.
AB  - OBJECTIVES: The aim of the study was to assess whether gastrostomy placement
      before 18 months of age results in a greater increase in z-score for weight and
      to assess whether admission rates were reduced postgastrostomy in this age group.
      DESIGN: Retrospective cross-sectional study. SETTING: Single-centre secondary
      care District General Hospital. PARTICIPANTS: All children with a neurodisability
      with a gastrostomy in situ in September 2011 were included. Those with primary
      neoplasia and undergoing chemo or radiotherapy or being palliated for an
      aggressive neurodegenerative disorder were excluded. Those with cystic fibrosis,
      primary congenital heart disease or Inflammatory bowel disease were also
      excluded. Forty-one children underwent final analysis. Twenty-four children
      underwent gastrostomy insertion less than 18 months and 17 children were older
      than 18 months. PRIMARY AND SECONDARY OUTCOME MEASURES: Primary outcome was z
      scores for weight immediately pregastrostomy and 12 months postgastrostomy.
      Secondary outcomes were hospital admission rates pregastrostomy and
      postgastrostomy. Values were compared for those with gastrostomy insertion less
      than or equal to 18 months against those older than 18 months at insertion.
      RESULTS: Z-score for weight increased significantly in both age groups. There was
      significantly increased mean difference in the z-score for weight of +1.33
      pregastrostomy and postgastrostomy in the less than 18 months age group as
      compared with an increased mean difference in the z-score for weight of +0.45 in
      the older age group (p=0.021). There was no significant difference in the
      admission rates postgastrostomy insertion in either age group. CONCLUSIONS:
      Gastrostomy insertion before 18 months of age results in greater z-score for
      weight gain in children with a neurodisability. This conclusion is limited by the
      lack of height and skin-fold thickness measurements. Further long-term matched
      control studies are required to determine the neurodevelopmental and clinical
      benefit of early gastrostomy placement in such children.

PMID- 23175742
TI  - Identification of PAN2 by quantitative proteomics as a leucine-rich repeat
      receptor-like kinase acting upstream of PAN1 to polarize cell division in maize.
AB  - Mechanisms governing the polarization of plant cell division are poorly
      understood. Previously, we identified pangloss1 (PAN1) as a leucine-rich repeat
      receptor-like kinase (LRR-RLK) that promotes the polarization of subsidiary
      mother cell (SMC) divisions toward the adjacent guard mother cell (GMC) during
      stomatal development in maize (Zea mays). Here, we identify pangloss2 (PAN2) as a
      second LRR-RLK promoting SMC polarization. Quantitative proteomic analysis
      identified a PAN2 candidate by its depletion from membranes of pan2 single and
      pan1;pan2 double mutants. Genetic mapping and sequencing of mutant alleles
      confirmed the identity of this protein as PAN2. Like PAN1, PAN2 has a
      catalytically inactive kinase domain and accumulates in SMCs at sites of GMC
      contact before nuclear polarization. The timing of polarized PAN1 and PAN2
      localization is very similar, but PAN2 acts upstream because it is required for
      polarized accumulation of PAN1 but is independent of PAN1 for its own
      localization. We find no evidence that PAN2 recruits PAN1 to the GMC contact site
      via a direct or indirect physical interaction, but PAN2 interacts with itself.
      Together, these results place PAN2 at the top of a cascade of events promoting
      the polarization of SMC divisions, potentially functioning to perceive or amplify
      GMC-derived polarizing cues.

PMID- 23175743
TI  - A galacturonic acid-containing xyloglucan is involved in Arabidopsis root hair
      tip growth.
AB  - Root hairs provide a model system to study plant cell growth, yet little is known
      about the polysaccharide compositions of their walls or the role of these
      polysaccharides in wall expansion. We report that Arabidopsis thaliana root hair
      walls contain a previously unidentified xyloglucan that is composed of both
      neutral and galacturonic acid-containing subunits, the latter containing the beta
      D-galactosyluronic acid-(1->2)-alpha-D-xylosyl-(1-> and/or alpha-L-fucosyl-(1->2)
      beta-D-galactosyluronic acid-(1->2)-alpha-D-xylosyl-(1->) side chains.
      Arabidopsis mutants lacking root hairs have no acidic xyloglucan. A loss-of
      function mutation in At1g63450, a root hair-specific gene encoding a family GT47
      glycosyltransferase, results in the synthesis of xyloglucan that lacks
      galacturonic acid. The root hairs of this mutant are shorter than those of the
      wild type. This mutant phenotype and the absence of galacturonic acid in the root
      xyloglucan are complemented by At1g63450. The leaf and stem cell walls of wild
      type Arabidopsis contain no acidic xyloglucan. However, overexpression of
      At1g63450 led to the synthesis of galacturonic acid-containing xyloglucan in
      these tissues. We propose that At1g63450 encodes XYLOGLUCAN-SPECIFIC
      GALACTURONOSYLTRANSFERASE1, which catalyzes the formation of the galactosyluronic
      acid-(1->2)-alpha-D-xylopyranosyl linkage and that the acidic xyloglucan is
      present only in root hair cell walls. The role of the acidic xyloglucan in root
      hair tip growth is discussed.

PMID- 23175744
TI  - Protein-protein and protein-membrane associations in the lignin pathway.
AB  - Supramolecular organization of enzymes is proposed to orchestrate metabolic
      complexity and help channel intermediates in different pathways. Phenylpropanoid
      metabolism has to direct up to 30% of the carbon fixed by plants to the
      biosynthesis of lignin precursors. Effective coupling of the enzymes in the
      pathway thus seems to be required. Subcellular localization, mobility, protein
      protein, and protein-membrane interactions of four consecutive enzymes around the
      main branch point leading to lignin precursors was investigated in leaf tissues
      of Nicotiana benthamiana and cells of Arabidopsis thaliana. CYP73A5 and CYP98A3,
      the two Arabidopsis cytochrome P450s (P450s) catalyzing para- and meta
      hydroxylations of the phenolic ring of monolignols were found to colocalize in
      the endoplasmic reticulum (ER) and to form homo- and heteromers. They moved along
      with the fast remodeling plant ER, but their lateral diffusion on the ER surface
      was restricted, likely due to association with other ER proteins. The connecting
      soluble enzyme hydroxycinnamoyltransferase (HCT), was found partially associated
      with the ER. Both HCT and the 4-coumaroyl-CoA ligase relocalized closer to the
      membrane upon P450 expression. Fluorescence lifetime imaging microscopy supports
      P450 colocalization and interaction with the soluble proteins, enhanced by the
      expression of the partner proteins. Protein relocalization was further enhanced
      in tissues undergoing wound repair. CYP98A3 was the most effective in driving
      protein association.

PMID- 23175747
TI  - Bioinformatics approaches and tools for metagenomic analysis. Editorial.

PMID- 23175745
TI  - Degradation of the endoplasmic reticulum by autophagy during endoplasmic
      reticulum stress in Arabidopsis.
AB  - In this article, we show that the endoplasmic reticulum (ER) in Arabidopsis
      thaliana undergoes morphological changes in structure during ER stress that can
      be attributed to autophagy. ER stress agents trigger autophagy as demonstrated by
      increased production of autophagosomes. In response to ER stress, a soluble ER
      marker localizes to autophagosomes and accumulates in the vacuole upon inhibition
      of vacuolar proteases. Membrane lamellae decorated with ribosomes were observed
      inside autophagic bodies, demonstrating that portions of the ER are delivered to
      the vacuole by autophagy during ER stress. In addition, an ER stress sensor,
      INOSITOL-REQUIRING ENZYME-1b (IRE1b), was found to be required for ER stress
      induced autophagy. However, the IRE1b splicing target, bZIP60, did not seem to be
      involved, suggesting the existence of an undiscovered signaling pathway to
      regulate ER stress-induced autophagy in plants. Together, these results suggest
      that autophagy serves as a pathway for the turnover of ER membrane and its
      contents in response to ER stress in plants.

PMID- 23175746
TI  - Genome-wide characterization of nonreference transposons reveals evolutionary
      propensities of transposons in soybean.
AB  - Preferential accumulation of transposable elements (TEs), particularly long
      terminal repeat retrotransposons (LTR-RTs), in recombination-suppressed
      pericentromeric regions seems to be a general pattern of TE distribution in
      flowering plants. However, whether such a pattern was formed primarily by
      preferential TE insertions into pericentromeric regions or by selection against
      TE insertions into euchromatin remains obscure. We recently investigated TE
      insertions in 31 resequenced wild and cultivated soybean (Glycine max) genomes
      and detected 34,154 unique nonreference TE insertions mappable to the reference
      genome. Our data revealed consistent distribution patterns of the nonreference
      LTR-RT insertions and those present in the reference genome, whereas the
      distribution patterns of the nonreference DNA TE insertions and the accumulated
      ones were significantly different. The densities of the nonreference LTR-RT
      insertions were found to negatively correlate with the rates of local genetic
      recombination, but no significant correlation between the densities of
      nonreference DNA TE insertions and the rates of local genetic recombination was
      detected. These observations suggest that distinct insertional preferences were
      primary factors that resulted in different levels of effectiveness of purifying
      selection, perhaps as an effect of local genomic features, such as recombination
      rates and gene densities that reshaped the distribution patterns of LTR-RTs and
      DNA TEs in soybean.

PMID- 23175748
TI  - Bioinformatic approaches for functional annotation and pathway inference in
      metagenomics data.
AB  - Metagenomic approaches are increasingly recognized as a baseline for
      understanding the ecology and evolution of microbial ecosystems. The development
      of methods for pathway inference from metagenomics data is of paramount
      importance to link a phenotype to a cascade of events stemming from a series of
      connected sets of genes or proteins. Biochemical and regulatory pathways have
      until recently been thought and modelled within one cell type, one organism, one
      species. This vision is being dramatically changed by the advent of whole
      microbiome sequencing studies, revealing the role of symbiotic microbial
      populations in fundamental biochemical functions. The new landscape we face
      requires a clear picture of the potentialities of existing tools and development
      of new tools to characterize, reconstruct and model biochemical and regulatory
      pathways as the result of integration of function in complex symbiotic
      interactions of ontologically and evolutionary distinct cell types.

PMID- 23175749
TI  - Object exploration at 6 and 9 months in infants with and without risk for autism.
AB  - During the first year of life, infants spend substantial amounts of time
      exploring objects they encounter in their daily environments. Perceptuo-motor
      information gained through these experiences provides a foundation for later
      developmental advances in cognition and language. This study aims to examine
      developmental trajectories of visual, oral, and manual object exploration in
      infants with and without risk for autism spectrum disorder before the age of 1
      year. A total of 31 infants, 15 of whom had an older sibling with autism and who
      were therefore at heightened risk for autism spectrum disorder, played with
      sounding and nonsounding rattles at 6 and 9 months of age. The results suggest
      that heightened-risk infants lag behind their low-risk peers in the exploration
      of objects. The findings are discussed in terms of how delays in object
      exploration in infancy may have cascading effects in other domains. 

PMID- 23175750
TI  - Examining restricted and repetitive behaviors in young children with autism
      spectrum disorder during two observational contexts.
AB  - This prospective study of the FIRST WORDS(r) Project examined restricted and
      repetitive behaviors in a sample of 55 toddlers at a mean age of 20 months who
      were later diagnosed with autism spectrum disorder. Restricted and repetitive
      behaviors were coded using the Repetitive Movement and Restricted Interest Scales
      in two video-recorded observation methods-structured sampling procedures in a
      clinic and naturalistic everyday activities at home. Measures of restricted and
      repetitive behaviors were higher in the clinic setting than in the home
      observation, especially for behaviors involving object use. Repetitive movements
      with objects in the clinic predicted nonverbal developmental scores and Autism
      Diagnostic Observation Schedule social affect scores at later follow-up. In
      contrast, repetitive movements with objects at home significantly predicted later
      Autism Diagnostic Observation Schedule restricted and repetitive behaviors
      scores. These results support the utility of the Repetitive Movement and
      Restricted Interest Scales to detect restricted and repetitive behaviors in
      toddlers and suggest that observations of restricted and repetitive behaviors in
      clinic and home settings may provide unique and important diagnostic information
      for improving early detection of autism spectrum disorder.

PMID- 23175751
TI  - The relationship between emotion recognition ability and social skills in young
      children with autism.
AB  - This study assessed the relationship between emotion recognition ability and
      social skills in 42 young children with autistic disorder aged 4-7 years. The
      analyses revealed that accuracy in recognition of sadness, but not happiness,
      anger or fear, was associated with higher ratings on the Vineland-II
      Socialization domain, above and beyond the influence of chronological age,
      cognitive ability and autism symptom severity. These findings extend previous
      research with adolescents and adults with autism spectrum disorders, suggesting
      that sadness recognition is also associated with social skills in children with
      autism. 

PMID- 23175752
TI  - Using the modified checklist for autism in toddlers in a well-child clinic in
      Turkey: adapting the screening method based on culture and setting.
AB  - We aimed to adapt the Modified Checklist for Autism in Toddlers to Turkish
      culture. The Modified Checklist for Autism in Toddlers was filled out
      independently by 191 parents while they were waiting for the well-child
      examination of their child. A high screen-positive rate was found. Because of
      this high false-positive rate, a second study was done in which the Modified
      Checklist for Autism in Toddlers was administered by health-care staff in a short
      interview with two groups of parents. The first group (the high-risk group)
      comprised 80 children aged 18-36 months, who were initially diagnosed with
      pervasive developmental disorders. The second group (the low-risk group)
      comprised 538 children of the same age, who were followed regularly by the well
      child clinic. Two screen positives were found in the low-risk group. These two
      children, a random sample of 120 children from the low-risk group, and all the
      high-risk group were invited to a clinical evaluation. The diagnostic power of
      the Modified Checklist for Autism in Toddlers was assessed against clinical
      diagnosis and the Childhood Autism Rating Scale. The positive predictive value of
      the Modified Checklist for Autism in Toddlers was found to be 75%. Our findings
      led us to conclude that the Modified Checklist for Autism in Toddlers is a useful
      tool in Turkey for screening of pervasive developmental disorders in primary
      care, but in our culture, it is completed more accurately when health-care
      personnel ask the parents the questions. This study shows that Modified Checklist
      for Autism in Toddlers screening should be adapted based on culture and setting. 

PMID- 23175753
TI  - Functional identification of sorting receptors involved in trafficking of soluble
      lytic vacuolar proteins in vegetative cells of Arabidopsis.
AB  - In eukaryotic cells, protein trafficking plays an essential role in biogenesis of
      proteins that belong to the endomembrane compartments. In this process, an
      important step is the sorting of organellar proteins depending on their final
      destinations. For vacuolar proteins, vacuolar sorting receptors (VSRs) and
      receptor homology-transmembrane-RING H2 domain proteins (RMRs) are thought to be
      responsible. Arabidopsis (Arabidopsis thaliana) contains seven VSRs. Among them,
      VSR1, VSR3, and VSR4 are involved in sorting storage proteins targeted to the
      protein storage vacuole (PSV) in seeds. However, the identity of VSRs for soluble
      proteins of the lytic vacuole in vegetative cells remains controversial. Here, we
      provide evidence that VSR1, VSR3, and VSR4 are involved in sorting soluble lytic
      vacuolar and PSV proteins in vegetative cells. In protoplasts from leaf tissues
      of vsr1vsr3 and vsr1vsr4 but not vsr5vsr6, and rmr1rmr2 and rmr3rmr4 double
      mutants, soluble lytic vacuolar (Arabidopsis aleurain-like protein:green
      fluorescent protein [GFP] and carboxypeptidase Y:GFP and PSV (phaseolin)
      proteins, but not the vacuolar membrane protein Arabidopsis
      betaFructosidase4:GFP, exhibited defects in their trafficking; they accumulated
      to the endoplasmic reticulum with an increased secretion into medium. The
      trafficking defects in vsr1vsr4 protoplasts were rescued by VSR1 or VSR4 but not
      VSR5 or AtRMR1. Furthermore, of the luminal domain swapping mutants between VSR1
      and VSR5, the mutant with the luminal domain of VSR1, but not that of VSR5,
      rescued the trafficking defects of Arabidopsis aleurain-like protein:GFP and
      phaseolin in vsr1vsr4 protoplasts. Based on these results, we propose that VSR1,
      VSR3, and VSR4, but not other VSRs, are involved in sorting soluble lytic
      vacuolar and PSV proteins for their trafficking to the vacuoles in vegetative
      cells.

PMID- 23175754
TI  - Structure of cellulose microfibrils in primary cell walls from collenchyma.
AB  - In the primary walls of growing plant cells, the glucose polymer cellulose is
      assembled into long microfibrils a few nanometers in diameter. The rigidity and
      orientation of these microfibrils control cell expansion; therefore, cellulose
      synthesis is a key factor in the growth and morphogenesis of plants. Celery
      (Apium graveolens) collenchyma is a useful model system for the study of primary
      wall microfibril structure because its microfibrils are oriented with unusual
      uniformity, facilitating spectroscopic and diffraction experiments. Using a
      combination of x-ray and neutron scattering methods with vibrational and nuclear
      magnetic resonance spectroscopy, we show that celery collenchyma microfibrils
      were 2.9 to 3.0 nm in mean diameter, with a most probable structure containing 24
      chains in cross section, arranged in eight hydrogen-bonded sheets of three
      chains, with extensive disorder in lateral packing, conformation, and hydrogen
      bonding. A similar 18-chain structure, and 24-chain structures of different
      shape, fitted the data less well. Conformational disorder was largely restricted
      to the surface chains, but disorder in chain packing was not. That is, in
      position and orientation, the surface chains conformed to the disordered lattice
      constituting the core of each microfibril. There was evidence that adjacent
      microfibrils were noncovalently aggregated together over part of their length,
      suggesting that the need to disrupt these aggregates might be a constraining
      factor in growth and in the hydrolysis of cellulose for biofuel production.

PMID- 23175756
TI  - A beta-mixture quantile normalization method for correcting probe design bias in
      Illumina Infinium 450 k DNA methylation data.
AB  - MOTIVATION: The Illumina Infinium 450 k DNA Methylation Beadchip is a prime
      candidate technology for Epigenome-Wide Association Studies (EWAS). However, a
      difficulty associated with these beadarrays is that probes come in two different
      designs, characterized by widely different DNA methylation distributions and
      dynamic range, which may bias downstream analyses. A key statistical issue is
      therefore how best to adjust for the two different probe designs. RESULTS: Here
      we propose a novel model-based intra-array normalization strategy for 450 k data,
      called BMIQ (Beta MIxture Quantile dilation), to adjust the beta-values of type2
      design probes into a statistical distribution characteristic of type1 probes. The
      strategy involves application of a three-state beta-mixture model to assign
      probes to methylation states, subsequent transformation of probabilities into
      quantiles and finally a methylation-dependent dilation transformation to preserve
      the monotonicity and continuity of the data. We validate our method on cell-line
      data, fresh frozen and paraffin-embedded tumour tissue samples and demonstrate
      that BMIQ compares favourably with two competing methods. Specifically, we show
      that BMIQ improves the robustness of the normalization procedure, reduces the
      technical variation and bias of type2 probe values and successfully eliminates
      the type1 enrichment bias caused by the lower dynamic range of type2 probes. BMIQ
      will be useful as a preprocessing step for any study using the Illumina Infinium
      450 k platform. AVAILABILITY: BMIQ is freely available from
      http://code.google.com/p/bmiq/. CONTACT: a.teschendorff@ucl.ac.uk SUPPLEMENTARY
      INFORMATION: Supplementary data are available at Bioinformatics online.

PMID- 23175755
TI  - Involvement of Arabidopsis ACYL-COENZYME A DESATURASE-LIKE2 (At2g31360) in the
      biosynthesis of the very-long-chain monounsaturated fatty acid components of
      membrane lipids.
AB  - The Arabidopsis (Arabidopsis thaliana) acyl-coenzyme A (CoA) desaturase-like
      (ADS) gene family contains nine genes encoding fatty acid desaturase-like
      proteins. The biological function of only one member of the family, fatty acid
      desaturase5 (AtADS3/FAD5, At3g15850), is known, and this gene encodes the
      plastidic palmitoyl-monogalactosyldiacylglycerol Delta7 desaturase. We cloned
      seven members of the gene family that are predicted not to have a chloroplast
      transit peptide and expressed them in the yeast Saccharomyces cerevisiae. All
      seven have previously undescribed desaturase activity on very-long-chain fatty
      acid (VLCFA) substrates and exhibit diverse regiospecificity, catalyzing
      introduction of double bonds relative to the methyl end of the molecule (n-x) at
      n-6 (AtADS4, At1g06350), n-7 (AtADS1.3, At1g06100 and AtADS4.2, At1g06360), n-9
      (AtADS1, At1g06080 and AtADS2, At2g31360) or Delta9 (relative to the carboxyl end
      of the molecule) positions (AtADS1.2, At1g06090 and AtADS1.4, At1g06120). Through
      forward and reverse genetics it was shown that AtADS2 is involved in the
      synthesis of the 24:1(n-9) and 26:1(n-9) components (X:Y, where X is chain length
      and Y is number of double bonds) of seed lipids, sphingolipids, and the membrane
      phospholipids phosphatidylserine, and phosphatidylethanolamine. Plants deficient
      in AtADS2 expression showed no obvious phenotype when grown under normal growing
      conditions, but showed an almost complete loss of phosphatidylethanolamine(42:4),
      phosphatidylserine(42:4), dihydroxy-monohexosylceramide(42:2)-2, trihydroxy
      monohexosylceramide(42:2)-3, and trihydroxy-glycosylinositolphosphoceramide(42:2)
      3, lipid species that contain the VLCFA 24:1(n-9), and trihydroxy
      glycosylinositolphosphoceramide(44:2)-3, a lipid containing 26:1(n-9). Acyl-CoA
      profiling of these plants revealed a major reduction in 24:1-CoA and a small
      reduction in 26:1-CoA. Overexpression of AtADS2 resulted in a substantial
      increase in the percentage of glycerolipid and sphingolipids species containing
      24:1 and a dramatic increase in the percentage of very-long-chain monounsaturated
      fatty acids in the acyl-CoA pool. Plants deficient in AtADS1 expression had
      reduced levels of 26:1(n-9) in seed lipids, but no significant changes in leaf
      phospholipids or sphingolipids were observed. These findings indicate that the 24
      carbon and 26-carbon monounsaturated VLCFAs of Arabidopsis result primarily from
      VLCFA desaturation, rather than by elongation of long chain monounsaturated fatty
      acids.

PMID- 23175757
TI  - An effective framework for reconstructing gene regulatory networks from genetical
      genomics data.
AB  - MOTIVATION: Systems Genetics approaches, in particular those relying on genetical
      genomics data, put forward a new paradigm of large-scale genome and network
      analysis. These methods use naturally occurring multi-factorial perturbations
      (e.g. polymorphisms) in properly controlled and screened genetic crosses to
      elucidate causal relationships in biological networks. However, although
      genetical genomics data contain rich information, a clear dissection of causes
      and effects as required for reconstructing gene regulatory networks is not easily
      possible. RESULTS: We present a framework for reconstructing gene regulatory
      networks from genetical genomics data where genotype and phenotype correlation
      measures are used to derive an initial graph which is subsequently reduced by
      pruning strategies to minimize false positive predictions. Applied to realistic
      simulated genetic data from a recent DREAM challenge, we demonstrate that our
      approach is simple yet effective and outperforms more complex methods (including
      the best performer) with respect to (i) reconstruction quality (especially for
      small sample sizes) and (ii) applicability to large data sets due to relatively
      low computational costs. We also present reconstruction results from real
      genetical genomics data of yeast. AVAILABILITY: A MATLAB implementation (script)
      of the reconstruction framework is available at www.mpi
      magdeburg.mpg.de/projects/cna/etcdownloads.html CONTACT: klamt@mpi
      magdeburg.mpg.de.

PMID- 23175758
TI  - A Lasso multi-marker mixed model for association mapping with population
      structure correction.
AB  - MOTIVATION: Exploring the genetic basis of heritable traits remains one of the
      central challenges in biomedical research. In traits with simple Mendelian
      architectures, single polymorphic loci explain a significant fraction of the
      phenotypic variability. However, many traits of interest seem to be subject to
      multifactorial control by groups of genetic loci. Accurate detection of such
      multivariate associations is non-trivial and often compromised by limited
      statistical power. At the same time, confounding influences, such as population
      structure, cause spurious association signals that result in false-positive
      findings. RESULTS: We propose linear mixed models LMM-Lasso, a mixed model that
      allows for both multi-locus mapping and correction for confounding effects. Our
      approach is simple and free of tuning parameters; it effectively controls for
      population structure and scales to genome-wide datasets. LMM-Lasso simultaneously
      discovers likely causal variants and allows for multi-marker-based phenotype
      prediction from genotype. We demonstrate the practical use of LMM-Lasso in genome
      wide association studies in Arabidopsis thaliana and linkage mapping in mouse,
      where our method achieves significantly more accurate phenotype prediction for
      91% of the considered phenotypes. At the same time, our model dissects the
      phenotypic variability into components that result from individual single
      nucleotide polymorphism effects and population structure. Enrichment of known
      candidate genes suggests that the individual associations retrieved by LMM-Lasso
      are likely to be genuine. AVAILABILITY: Code available under
      http://webdav.tuebingen. mpg.de/u/karsten/Forschung/research.html. CONTACT:
      rakitsch@tuebingen.mpg.de, ippert@microsoft.com or stegle@ebi.ac.uk SUPPLEMENTARY
      INFORMATION: Supplementary data are available at Bioinformatics online.

PMID- 23175759
TI  - Physical inactivity is associated with low self efficacy and social support among
      patients with hypertension in Nigeria.
AB  - BACKGROUND Physical inactivity is a major factor in the development of many
      chronic illnesses, including hypertension. Evidence highlighting links among
      physical activity participation and psychosocial constructs such as self
      efficacy, social support and perceived barriers among hypertensive patients in
      the Nigerian population is scarce. This study explored the associations between
      physical activity and each of self efficacy, social support and perceived
      barriers. METHODS Two hundred and twelve patients receiving treatment in two
      tertiary health institutions located in Ekiti State, Nigeria were surveyed cross
      sectionally. Physical activity level, self efficacy, social support and perceived
      barriers were measured with the International Physical Activity Questionnaire,
      Exercise Self-Efficacy Scale, Medical Outcomes Social Support Scale and Exercise
      Benefits and Barrier Scale respectively. RESULTS Level of physical activity was
      significantly associated with self efficacy (r(s) = 0.67, p < 0.01, = 0.45) and
      social support (r(s) = 0.80, p < 0.01, = 0.64), with most participants (56.1%)
      being physically inactive. However, no association was found between physical
      activity level and perceived barriers (r(s) = 0.07, p > 0.01, = 0.005).
      CONCLUSION Most of the hypertensive patients presented with low levels of
      physical activity. Physical activity was associated with psychosocial constructs
      including self efficacy and social support but not with perceived barriers.

PMID- 23175760
TI  - Reducing uncertainty about the public health implications of Escherichia coli
      serogroup O104:H4.

PMID- 23175761
TI  - Group- and genotype-specific neutralizing antibody responses against respiratory
      syncytial virus in infants and young children with severe pneumonia.
AB  - The effect of genetic variation on the neutralizing antibody response to
      respiratory syncytial virus (RSV) is poorly understood. In this study, acute- and
      convalescent-phase sera were evaluated against different RSV strains. The
      proportion of individuals with homologous seroconversion was greater than that
      among individuals with heterologous seroconversion among those infected with RSV
      group A (50% vs 12.5%; P = .0005) or RSV group B (40% vs 8%; P = .008).
      Seroconversion to BA genotype or non-BA genotype test viruses was similar among
      individuals infected with non-BA virus (35% vs 50%; P = .4) or BA virus (50% vs
      65%; P = .4). The RSV neutralizing response is group specific. The BA-associated
      genetic change did not confer an ability to escape neutralizing responses to
      previous non-BA viruses.

PMID- 23175762
TI  - Protection against henipavirus infection by use of recombinant adeno-associated
      virus-vector vaccines.
AB  - Nipah virus (NiV) and Hendra virus (HeV) are closely related, recently emerged
      paramyxoviruses that are capable of causing considerable morbidity and mortality
      in several mammalian species, including humans. Henipavirus-specific vaccines are
      still commercially unavailable, and development of novel antiviral strategies to
      prevent lethal infections due to henipaviruses is highly desirable. Here we
      describe the development of adeno-associated virus (AAV) vaccines expressing the
      NiV G protein. Characterization of these vaccines in mice demonstrated that a
      single intramuscular AAV injection was sufficient to induce a potent and long
      lasting antibody response. Translational studies in hamsters further demonstrated
      that all vaccinated animals were protected against lethal challenge with NiV. In
      addition, this vaccine induced a cross-protective immune response that was able
      to protect 50% of the animals against a challenge by HeV. This study presents a
      new efficient vaccination strategy against henipaviruses and opens novel
      perspectives on the use of AAV vectors as vaccines against emergent diseases.

PMID- 23175763
TI  - Carrier prevalence, secondary household transmission, and long-term shedding in 2
      districts during the Escherichia coli O104:H4 outbreak in Germany, 2011.
AB  - BACKGROUND: From May through July 2011, Germany experienced a large outbreak of
      Shiga toxin-producing Escherichia coli (STEC) O104:H4 infection. Our objective
      was to identify the prevalence of STEC O104:H4 carriers in households in highly
      affected areas, the rate of secondary household transmissions, and the duration
      of long-term shedding. METHODS: In a cross-sectional study, we recruited case and
      control households to determine STEC household prevalence. We then conducted a
      prospective cohort study (households with >= 2 members and >= 1 case) to
      determine rates of household transmission and shedding duration. RESULTS: For
      part 1, we recruited 57 case households (62 case patients and 93 household
      contacts) and 36 control households (89 household members). We only detected
      cases in previously known case households and identified 1 possible adult-to
      adult household transmission. For part 2, we followed 14 households and 20
      carriers. No secondary household transmission was detected in the prospective
      follow-up period. In 1 adult carrier, shedding lasted >7 months. However, the
      median estimated shedding time was 10-14 days (95% confidence interval, 0-33
      days). Three carriers showed intermittent shedding. CONCLUSIONS: The prevalence
      of STEC O104:H4 carriers even in highly affected areas appears to be low. Despite
      prolonged shedding in some patients, secondary adult-to-adult household
      transmissions seem to be rare events in the postdiarrheal disease phase.

PMID- 23175764
TI  - Human papillomavirus infection and laryngeal cancer risk: a systematic review and
      meta-analysis.
AB  - BACKGROUND: A number of molecular epidemiological studies have been conducted to
      explore the association of human papillomavirus (HPV) infection with laryngeal
      cancer. However, the findings are heterogeneous. METHODS: We systematically
      reviewed studies on HPV infection and laryngeal cancer published up to 15 May
      2012 and quantitatively summarized the prevalence of HPV infection and its
      association with the risk of laryngeal cancer by means of meta-analysis. RESULTS:
      In total, 55 eligible studies were included. The overall HPV prevalence in
      laryngeal cancer tissues was 28.0% (95% confidence interval [CI], 23.5%-32.9%). A
      total of 26.6% laryngeal cancer patients were infected with high-risk HPV types
      only, and HPV-16 was most frequently observed type, with a prevalence of 19.8%
      (95% CI, 15.7%-24.6%). The meta-analysis based on 12 eligible case-control
      studies suggests a strong association between HPV infection and laryngeal
      squamous cell carcinoma, with a summary odds ratio (OR) of 5.39 (95% CI, 3.25
      8.94). Different magnitudes of association were observed for HPV-16 (OR, 6.07;
      95% CI, 3.44-10.70) and HPV-18 (OR = 4.16; 95% CI, .87-20.04; P < .01).
      Stratified analyses were performed with respect to HPV genotypes and
      characteristics of the study population. CONCLUSIONS: HPV infection, especially
      infection due to the high-risk type HPV-16, was found to be significantly
      associated with the risk of laryngeal squamous cell carcinoma.

PMID- 23175765
TI  - Pneumococcal capsular switching: a historical perspective.
AB  - BACKGROUND: Changes in serotype prevalence among pneumococcal populations result
      from both serotype replacement and serotype (capsular) switching. Temporal
      changes in serotype distributions are well documented, but the contribution of
      capsular switching to such changes is unknown. Furthermore, it is unclear to what
      extent vaccine-induced selective pressures drive capsular switching. METHODS:
      Serotype and multilocus sequence typing data for 426 pneumococci dated from 1937
      through 2007 were analyzed. Whole-genome sequence data for a subset of isolates
      were used to investigate capsular switching events. RESULTS: We identified 36
      independent capsular switch events, 18 of which were explored in detail with
      whole-genome sequence data. Recombination fragment lengths were estimated for 11
      events and ranged from approximately 19.0 kb to >= 58.2 kb. Two events took place
      no later than 1960, and the imported DNA included the capsular locus and the
      nearby penicillin-binding protein genes pbp2x and pbp1a. CONCLUSIONS: Capsular
      switching has been a regular occurrence among pneumococcal populations throughout
      the past 7 decades. Recombination of large DNA fragments (>30 kb), sometimes
      including the capsular locus and penicillin-binding protein genes, predated both
      vaccine introduction and widespread antibiotic use. This type of recombination
      has likely been an intrinsic feature throughout the history of pneumococcal
      evolution.

PMID- 23175767
TI  - Innovative trial designs to improving tuberculosis drug development.

PMID- 23175766
TI  - Natural killer cell functional defects in pediatric patients with severe and
      recurrent herpesvirus infections.
AB  - Natural killer (NK) cells play a critical role in the host defense against
      herpesviruses. Although herpesviruses are ubiquitous in human populations, only a
      minority of people experience severe recurrent infections. We hypothesize that
      uncharacterized NK cell functional deficits predispose individuals to more
      significant or frequent herpesvirus infections and reactivations. To investigate
      this hypothesis, we broadly analyzed NK cell phenotype and functional responses
      in a cohort of predominantly pediatric patients with recurrent and/or severe
      herpesvirus infections and compared them to a healthy control population. Our
      results identified no global differences in cytolysis, degranulation, interferon
      gamma production, or surface receptor upregulation following cytokine
      stimulation. However, abnormal NK cell functional responses were observed in
      nearly one-third of patients (including 3 with hyporesponsiveness to activating
      signals and 1 with markedly decreased CD11b expression associated with reduced
      cytotoxicity and degranulation), which might contribute to those individuals'
      susceptibility to herpesvirus infections.

PMID- 23175768
TI  - Reply to Dodd and Proschan.

PMID- 23175769
TI  - Immune response to hepatitis B virus vaccination among HIV-1 infected and
      uninfected adults in Kenya.
AB  - BACKGROUND: In studies from high-income countries, human immunodeficiency virus
      type 1 (HIV-1)-infected persons have diminished responses to hepatitis B virus
      (HBV) vaccination, compared with HIV-1-uninfected persons, but data from other
      settings are limited. METHODS: We compared the immune response to HBV vaccination
      among HIV-1-infected and HIV-1-uninfected Kenyan adults and assessed the response
      of HIV-1-infected initial nonresponders to revaccination with a standard HBV
      vaccine series. RESULTS: Of 603 participants, 310 (51.4%) were HIV-1-infected,
      for whom the median CD4(+) T-cell count was 557 cells/MUL (interquartile range,
      428-725 cells/MUL); none were receiving antiretroviral therapy. Nonresponse to
      HBV vaccine was higher among HIV-1-infected participants, compared with HIV-1
      uninfected participants (35.8% vs 14.3%; odds ratio, 3.33; P < .001). Of 102 HIV
      1-infected initial nonresponders, 88 (86.3%) responded to revaccination, for an
      overall response, including to revaccination, of 94.9%. Among HIV-1-infected
      individuals, lower CD4(+) T-cell counts and male sex were independent predictors
      of nonresponse to initial vaccination, and lower body mass index, higher plasma
      HIV-1 RNA levels, and longer time to revaccination predicted nonresponse to
      revaccination. CONCLUSIONS: Kenyan adults had similar HBV vaccination responses
      as persons from high-income countries. Timely revaccination of HIV-1-infected
      nonresponders increased response to the vaccine to 95%.

PMID- 23175770
TI  - Zebrafish dmrta2 regulates the expression of cdkn2c in spermatogenesis in the
      adult testis.
AB  - The exact function of the doublesex and mab-3 related transcription factor-like
      family a2 gene (dmrta2) has remained largely unknown possibly because of its
      functional redundancy with dmrta1 in most vertebrates. In this study, dmrta1 was
      demonstrated to likely be absent in the zebrafish genome, which facilitated our
      functional analysis of dmrta2 in this model organism. To analyze its gene
      function in embryos and adults, we generated a mutant form of Dmrta2 (R106Q,
      Dmrta2(RQ)) with its in vitro DNA-binding capacity abolished and a transgenic
      line for the inducible expression of this mutant Dmrta2(RQ) upon doxycycline
      (Dox) treatment. Preferential dmrta2 expression was detected in the developing
      brain during embryogenesis and in the adult testis. During embryogenesis,
      Dmrta2(RQ) expression caused severe embryonic development defects and dramatic
      expression changes of two telencephalic marker genes, fibroblast growth factor 8a
      (fgf8a), and empty spiracles homolog 1 (emx1). In adults, the inducible
      Dmrta2(RQ) expression occurred specifically in the adult testis and recapitulated
      the endogenous dmrta2 expression in this organ. Intriguingly, adult males
      expressing dmrta2(RQ) showed normal spermatogenesis and were fertile, but the
      expression of cyclin-dependent kinase inhibitor 2C (cdkn2c), which is
      evolutionarily clustered with dmrta2, was significantly suppressed during
      spermatogenesis. Further protein-binding and promoter mutation analysis indicated
      that a putative Dmrta2-binding site on the cdkn2c promoter was required for
      sustaining the normal expression of cdkn2c during zebrafish spermatogenesis,
      suggesting that Dmrta2 might regulate the expression of cdkn2c.

PMID- 23175771
TI  - Wnt6 is essential for stromal cell proliferation during decidualization in mice.
AB  - Postimplantation uterine development involves extensive stromal cell
      proliferation and decidual transformation with polyploidization, which is
      essential for normal pregnancy establishment. However, it remains largely unknown
      how stromal proliferation versus decidual polyploidization is differentially
      regulated during decidualization. Utilizing Wnt6-mutant mice, we show here that
      Wnt6 deficiency impairs stromal cell proliferation without much adverse effects
      on decidual polyploidization. Applying a primary stromal cell culture model, we
      further reveal that loss of Wnt6 prolongs the cell cycle length via
      downregulating cyclin B1 expression, thus attenuating stromal cell proliferation.
      Our study provides the first genetic evidence that Wnt6 is critical for normal
      stromal cell proliferation in mice, highlighting the concept that there are
      differential machineries governing the process of stromal cell proliferation
      versus decidual transformation during early pregnancy. This finding has high
      clinical relevance because Wnt signaling is known to be important for human
      implantation and endometrial function.

PMID- 23175772
TI  - Vasoactive intestinal peptide can promote the development of neonatal rat
      primordial follicles during in vitro culture.
AB  - Recruitment of primordial follicles is essential for female fertility. Some of
      the intraovarian growth factors involved in the initiation of primordial follicle
      growth have been identified, but the exact mechanisms regulating follicle
      activation are poorly understood. Strong evidence indicates that vasoactive
      intestinal peptide (VIP), a neuropeptide found in ovarian nerves, plays a role in
      the physiology of follicle development and function. The aim of the present study
      was to determine whether VIP might regulate the activation and growth of neonatal
      rat primordial follicles in an in vitro culture system. Ovaries from 4-day-old
      rats were cultured for 14 days in medium containing 10(-7) M VIP. At the end of
      the culture, the developmental stages and viability of the follicles were
      evaluated using histological sections. Immunohistochemistry studies for
      proliferating cell nuclear antigen (PCNA) were performed to assess the mitotic
      activity of granulosa cells. In addition, the expression level of kit ligand (KL)
      mRNA was examined after culture. Histology showed that primordial follicles could
      survive and start to grow in vitro. The proportion of primordial follicles was
      decreased and the proportion of early primary follicles increased after in vitro
      culture with VIP. Immunolocalization of PCNA showed that follicle growth was
      initiated after VIP treatment. The expression level of KL mRNA was increased in
      the VIP treatment group. Thus, VIP can promote primordial follicle development,
      possibly mediated in part through upregulating the expression of KL.

PMID- 23175773
TI  - Estrogen receptors alpha and beta in male and female gerbil prostates.
AB  - The Mongolian gerbil (Meriones unguiculatus, Gerbilinae: Muridae) is useful for
      prostate studies, because both males and females spontaneously develop prostatic
      disorders with age. Estrogens regulate prostate homeostasis via two estrogen
      receptors, ER alpha (ESR1) and ER beta (ESR2), but the cellular distribution and
      regulation of these receptors in the gerbil prostate has not been described. Both
      receptors were localized by immunohistochemistry in the ventral prostate of
      intact male and female gerbils, in males 7 and 21 days after castration, and in
      females treated with testosterone for 7 and 21 days. In male and female adult
      gerbils, ER alpha was detected mainly in prostatic stromal cells, whereas ER beta
      was present mostly in secretory and basal cells. More ER alpha-positive stromal
      cells were found in females than in males, as was a reduction toward the male
      value in females treated with testosterone. Castration did not alter ER alpha
      expression. Testosterone was necessary for maintenance of ER beta in the male
      prostate epithelium: ER beta expression declined markedly in prostates of males
      older than 1 yr, and castration of 4-mo-old males caused a reduction in ER beta
      to levels seen in 1-yr-old males. Because ER beta is an antiproliferative
      receptor, its loss with age may predispose the aging gerbil to proliferative
      diseases of the prostate.

PMID- 23175774
TI  - Glucose-regulated protein, 78-kilodalton is a modulator of luteinizing hormone
      receptor expression in luteinizing granulosa cells in rats.
AB  - Glucose-regulated protein, 78-kilodalton (GRP78) is a molecular chaperone that
      exists in the endoplasmic reticulum and is involved in the assembly,
      transportation, and folding of proteins. Previously, GRP78 was reported to
      associate with gonadotropin receptors. However, little is known about how GRP78
      is involved in the regulation of luteinizing hormone receptor (LHR). Thus, in
      this study, we investigated the significance of GRP78 for the induction of LHR in
      rat luteinizing granulosa cells. Western blot analysis of rat LHR expressed in
      HEK293 cells revealed that the protein levels of LHR were increased, depending on
      the increment of GRP78 protein. In both in vivo and in vitro experiments, the
      GRP78 mRNA level peaked while LHR mRNA was down-regulated by human chorionic
      gonadotropin (hCG). To examine the time-dependent localization of GRP78 in vivo,
      immunohistochemistry was performed. GRP78 was expressed mainly in granulosa
      cells, and the GRP78 protein peaked 18 h after the ovulatory dose of hCG
      injection in equine chorionic gonadotropin-primed immature rats. To ascertain the
      role of GRP78 in LHR after down-regulation, small interfering GRP78 was
      transfected to cultured rat granulosa cells, demonstrating that knockdown of the
      GRP78 protein level impaired the recovery of cell surface LHR from down
      regulation that negatively affected progesterone synthesis. Moreover, luciferase
      assays showed that CRE mediated the hCG-induced promoter activity of GRP78 in rat
      luteinizing granulosa cells. These results reveal a novel mechanism of LHR by
      GRP78 in the early stage of corpus lustrum formation, which may be an important
      factor in the recovery of LHR after the down-regulation.

PMID- 23175775
TI  - Wiring the developing heart: a serious matter for adulthood.

PMID- 23175776
TI  - PPARgamma coactivator-1alpha contributes to exercise-induced regulation of
      intramuscular lipid droplet programming in mice and humans.
AB  - Intramuscular accumulation of triacylglycerol, in the form of lipid droplets
      (LD), has gained widespread attention as a hallmark of metabolic disease and
      insulin resistance. Paradoxically, LDs also amass in muscles of highly trained
      endurance athletes who are exquisitely insulin sensitive. Understanding the
      molecular mechanisms that mediate the expansion and appropriate metabolic control
      of LDs in the context of habitual physical activity could lead to new therapeutic
      opportunities. Herein, we show that acute exercise elicits robust upregulation of
      a broad program of genes involved in regulating LD assembly, morphology,
      localization, and mobilization. Prominent among these was perilipin-5, a
      scaffolding protein that affects the spatial and metabolic interactions between
      LD and their surrounding mitochondrial reticulum. Studies in transgenic mice and
      primary human skeletal myocytes established a key role for the exercise
      responsive transcriptional coactivator PGC-1alpha in coordinating intramuscular
      LD programming with mitochondrial remodeling. Moreover, translational studies
      comparing physically active versus inactive humans identified a remarkably strong
      association between expression of intramuscular LD genes and enhanced insulin
      action in exercise-trained subjects. These results reveal an intimate molecular
      connection between intramuscular LD biology and mitochondrial metabolism that
      could prove relevant to the etiology and treatment of insulin resistance and
      other disorders of lipid imbalance.

PMID- 23175777
TI  - Differential effects of estrogen/androgen on the prevention of nonalcoholic fatty
      liver disease in the male rat.
AB  - It is important to clarify the distinct contributions of estrogen/estrogen
      receptor (ER) and androgen/androgen receptor (AR) signaling and their reciprocal
      effects on the regulation of hepatic lipid homeostasis. We studied the molecular
      mechanisms underlying the preventive effects of estradiol (E2),
      dihydrotestosterone (DHT), or E2+DHT on high-fat diet-induced nonalcoholic fatty
      liver disease (NAFLD) in an orchidectomized Sprague-Dawley (SD) rat model. E2 is
      shown to be associated with decreased fatty acid synthesis in hepatic zone 3
      specific manner by increasing the phosphorylation of acetyl coenzyme-A
      carboxylase via an ERalpha-mediated pathway. DHT is shown to be associated with
      decreased lipid accumulation and cholesterol synthesis in a hepatic zone 1
      specific manner by increasing expression of carnitine palmitotyltransferase1 and
      phosphorylation of 3-hydroxy-3-methyl-glutaryl-CoA reductase via an AR-mediated
      pathway. E2+DHT showed an additive positive effect and normalized all three
      impaired zones of the liver. Gene expression changes in human severe liver
      steatosis were similar to those of experimental rat NAFLD. Steroids reversed the
      histopathological NAFLD changes, likely by decreasing fatty acid and cholesterol
      synthesis and increasing beta-oxidation. The diverse steroid effects (ER/AR) on
      NAFLD prevention in male rats indicate the potential applicability of ER/AR
      modulators for NAFLD treatment.

PMID- 23175779
TI  - An overview of health-promoting compounds of broccoli (Brassica oleracea var.
      italica) and the effect of processing.
AB  - Broccoli offers many heath-promoting properties owing to its content of
      antioxidant and anticarcinogenic compounds. The concentration and bioavailability
      of polyphenols, glucosinolates, sulforaphane and selenium depend on plant
      biochemistry, cultivation strategy and type of processing. In this article, the
      main biochemical properties of broccoli are reviewed regarding their health
      promoting effects. Additionally, the way these properties are affected by
      processing is discussed. Steaming and drying result in an apparent increment of
      sulforaphane content as well as antioxidant activity, most likely due to an
      increase of the extractability of antioxidants and sulforaphane. Freezing and
      boiling diminish polyphenols concentration, mainly due to volatilization and
      leaching into the cooking water. In view of these results, the optimization of
      broccoli processing in order to maximize the content of bioactive compounds
      should be possible. The effect of processing on selenium compounds has been
      poorly studied so far, and therefore this topic should be investigated in the
      future. Finally, the effect of operating conditions in different drying processes
      on the content of bioactive compounds in broccoli should be investigated in a
      greater depth.

PMID- 23175778
TI  - Atypical antipsychotics alter cholesterol and fatty acid metabolism in vitro.
AB  - Haloperidol, a typical antipsychotic, has been shown to inhibit cholesterol
      biosynthesis by affecting Delta(7)-reductase, Delta(8,7)-isomerase, and Delta(14)
      reductase activities, which results in the accumulation of different sterol
      intermediates. In the present work, we investigated the effects of atypical or
      second-generation antipsychotics (SGA), such as clozapine, risperidone, and
      ziprasidone, on intracellular lipid metabolism in different cell lines. All the
      SGAs tested inhibited cholesterol biosynthesis. Ziprasidone and risperidone had
      the same targets as haloperidol at inhibiting cholesterol biosynthesis, although
      with different relative activities (ziprasidone > haloperidol > risperidone). In
      contrast, clozapine mainly affected Delta(24)-reductase and Delta(8,7)-isomerase
      activities. These amphiphilic drugs also interfered with the LDL-derived
      cholesterol egress from the endosome/lysosome compartment, thus further reducing
      the cholesterol content in the endoplasmic reticulum. This triggered a
      homeostatic response with the stimulation of sterol regulatory element-binding
      protein (SREBP)-regulated gene expression. Treatment with SGAs also increased the
      synthesis of complex lipids (phospholipids and triacylglycerides). Once the
      antipsychotics were removed from the medium, a rebound in the cholesterol
      biosynthesis rate was detected, and the complex-lipid synthesis further
      increased. In this condition, apolipoprotein B secretion was also stimulated as
      demonstrated in HepG2 cells. These effects of SGAs on lipid homeostasis may be
      relevant in the metabolic side effects of antipsychotics, especially
      hypertriglyceridemia.

PMID- 23175780
TI  - Fatty acid composition in hybrid pigs as based on local fatty Lithuanian breed
      and wild boar.
AB  - The study was designed to investigate the fatty acid composition in longissimus
      dorsi (LD) and semimembranosus muscles (SM) and subcutaneous tissue of hybrid
      (1/4 Lithuanian indigenous wattle, 1/4 wild boar and 1/2 Yorkshire or 1/2
      Landrace) pigs. The SM showed a tendency to have lower contents of
      monounsaturated fatty acids (MUFA) and higher contents of polyunsaturated fatty
      acids (PUFA) than the LD muscle. No statistically significant differences were
      observed between the muscles in lipid quality indices, i.e., atherogenic (AI) and
      thrombogenix (TI) indices and the ratio of hypocholesterolemic and
      hypercholesterolemic fatty acids (h/H). In the SM, the content of PUFA from
      Yorkshire-sired hybrids was relatively 47.8% higher, including C18:2n-6, C20:4n-6
      and DPA (C22:5n-3) that were higher, respectively, by 44.3%, 86.6% and 51.6% in
      comparison with those from Landrace-sired hybrids. The gilts had a lower content
      of MUFA, including C18:1 and C20:1n-9 fatty acids in the LD muscle and tended to
      have a higher content of PUFA in the SM compared to the barrows. Neither the
      terminal breed in crossing, nor the gender had any significant effects on the
      proportions of total saturated, MUFA and PUFA in the subcutaneous tissue.

PMID- 23175781
TI  - Application of edible coating and acidic washing for extending the storage life
      of mushrooms (Agaricus bisporus).
AB  - Hydrocolloid-based materials have been extensively used to coat fruit and
      vegetables to prolong shelf-life. The effects of different concentrations of
      acidic washing (acetic, ascorbic, citric and malic acids) followed by coating
      with gum arabic (GA), carboxymethyl cellulose and emulsified gum arabic (EGA)
      were evaluated on the weight loss (WL), firmness and color of mushroom. The WL of
      the uncoated mushrooms was significantly (p < 0.05) greater than that of the
      coated ones, and the minimum WL was obtained with EGA coating. The mushrooms
      washed with malic and ascorbic acids showed minimum and maximum of WL,
      respectively. Loss in firmness of the EGA-coated mushrooms was by 21% (the
      minimum of loss), while loss value of the uncoated ones was by 39% (the maximum
      of loss). Firmness of mushrooms was not influenced by the acid type.
      Concentration of the acid significantly (p < 0.05) influenced the firmness of
      mushrooms, and at the lowest concentration of acid (1%), the mushrooms tissue was
      firmest. The L* value of the mushrooms coated with GA was higher than that of
      others. A significant (p < 0.05) decrease in L* value and a significant (p <
      0.05) increase in a* and b* values occurred in the mushrooms washed with acetic
      acid. Overall, washing with 1% citric or malic acid followed by coating with EGA
      resulted in minimum decrease in WL and firmness of the mushrooms.

PMID- 23175782
TI  - Viscozyme L action on soy slurry affects carbohydrates and antioxidant properties
      of silken tofu.
AB  - This study investigated the enzymatic treatment of soy slurry using Viscozyme L
      to hydrolyze the carbohydrates. The optimum temperature of Viscozyme L action was
      55  degrees C. The increase of glucose and galactose content in tofu (1.36 and
      0.19 g/100 g, respectively) confirmed the Viscozyme activity on soy slurry when
      compared to the control. The treated tofu had more total phenolics than the
      control (173 and 161 mg gallic acid equivalents/100 g freeze-dried tofu,
      respectively) and higher antioxidant activity by the 2,2'-azinobis(3
      ethylbenzothiazoline-6-sulfonic acid) diammonium salt and 1,1-diphenyl-2
      picryhydrazyl,2,2-diphenyl-1-picryhydrazyl radical tests. Total reducing sugar
      (glucose equivalents) content in treated tofu was approximately four times higher
      than that in the control under the optimum conditions (30 Fungal Beta-Glucanase
      units/10 g solids, 55  degrees C, 30 min). The tofus differed in the sensory
      analysis for soy odor and surface uniformity, but there was no preference for one
      over the other.

PMID- 23175783
TI  - Changes in quality and biochemical parameters in 'Idared' apples during prolonged
      shelf life and 1-MCP treatment.
AB  - In this study, changes in quality and various biochemical parameters of 'Idared'
      apples during prolonged shelf life period after ultra-low oxygen (ULO) storage
      were investigated. Additionally, the impact of the postharvest application of 1
      methylcyclopropene (1-MCP) on different parameters was evaluated. After the
      harvest, apples were stored in the ULO storage for 6 months and then exposed to
      room temperature. Fruit firmness, peel color, and changes in sugars, organic
      acids and phenolics were monitored during the 3 weeks of shelf life. Malic acid,
      sugars and firmness decreased at room temperature. However, the color of the
      apples remained unchanged. The level of citric and ascorbic acid remained
      constant. Levels of phenolics in the peel increased significantly, whereas
      remained constant in the pulp of apples. 1-MCP treatment resulted in higher
      amounts of fructose and glucose, malic acid and greater firmness of apples.
      However, 1-MCP did not influence the phenolic content, ascorbic acid or color.
      The results obtained indicate that the content of different health-promoting
      compounds of apples does not change dramatically at room temperature. At the same
      time these results suggest that 1-MCP could be useful for maintaining certain
      quality and biochemical parameters and might extend the shelf life of apples.

PMID- 23175784
TI  - Self-produced exopolysaccharide is a signal that stimulates biofilm formation in
      Pseudomonas aeruginosa.
AB  - Bacteria have a tendency to attach to surfaces and grow as structured communities
      called biofilms. Chronic biofilm infections are a problem because they tend to
      resist antibiotic treatment and are difficult to eradicate. Bacterial biofilms
      have an extracellular matrix that is usually composed of a mixture of
      polysaccharides, proteins, and nucleic acids. This matrix has long been assumed
      to play a passive structural and protective role for resident biofilm cells. Here
      we show that this view is an oversimplification and that the biofilm matrix can
      play an active role in stimulating its own synthesis. Working with the model
      biofilm bacterium Pseudomonas aeruginosa, we found that Psl, a major biofilm
      matrix polysaccharide for this species, acts as a signal to stimulate two
      diguanylate cyclases, SiaD and SadC, to produce the intracellular secondary
      messenger molecule c-di-GMP. Elevated intracellular concentrations of c-di-GMP
      then lead to the increased production of Psl and other components of the biofilm.
      This mechanism represents a unique positive feedback regulatory circuit, where
      the expression of an extracellular polysaccharide promotes biofilm growth in a
      manner analogous to autocrine signaling in eukaryotes.

PMID- 23175785
TI  - A switch between DNA polymerases delta and lambda promotes error-free bypass of 8
      oxo-G lesions.
AB  - 7,8-Dihydro-8-oxoguanine (8-oxo-G) is a highly abundant and mutagenic lesion.
      Replicative DNA polymerases (pols) are slowed down at 8-oxo-G and insert both
      correct cytosine (C) and incorrect adenine (A) opposite 8-oxo-G, but they
      preferentially extend A:8-oxo-G mispairs. Nevertheless, 8-oxo-G bypass is fairly
      accurate in vivo. Thus, the question how correct bypass of 8-oxo-G lesions is
      accomplished despite the poor extension of C:8-oxo-G base pairs by replicative
      pols remains unanswered. Here we show that replicative pol delta pauses in front
      of 8-oxo-G and displays difficulties extending from correct C:8-oxo-G in contrast
      to extension from incorrect A:8-oxo-G. This leads to stalling of pol delta at 8
      oxo-G after incorporation of correct C. This stalling at C:8-oxo-G can be
      overcome by a switch from pol delta to pols lambda, beta, or eta, all of which
      are able to assist pol delta in 8-oxo-G bypass by translesion synthesis (TLS).
      Importantly, however, only pol lambda selectively catalyzes the correct TLS past
      8-oxo-G, whereas pols beta and eta show no selectivity and even preferentially
      enhance incorrect TLS. The selectivity of pol lambda to promote the correct
      bypass depends on its N-terminal domain. Furthermore, pol lambda(-/-) mouse
      embryonic fibroblast extracts display reduced 8-oxo-G TLS. Finally, the correct
      bypass of 8-oxo-G in gapped plasmids in mouse embryonic fibroblasts and HeLa
      cells is promoted in the presence of pol lambda. Our findings suggest that even
      though 8-oxo-G is not a blocking lesion per se, correct replication over 8-oxo-G
      is promoted by a pol switch between pols delta and lambda.

PMID- 23175786
TI  - Conservation of NLR-triggered immunity across plant lineages.
AB  - The nucleotide-binding domain and leucine-rich repeat (NLR) family of plant
      receptors detects pathogen-derived molecules, designated effectors, inside host
      cells and mediates innate immune responses to pathogenic invaders. Genetic
      evidence revealed species-specific coevolution of many NLRs with effectors from
      host-adapted pathogens, suggesting that the specificity of these NLRs is
      restricted to the host or closely related plant species. However, we report that
      an NLR immune receptor (MLA1) from monocotyledonous barley is fully functional in
      partially immunocompromised dicotyledonous Arabidopsis thaliana against the
      barley powdery mildew fungus, Blumeria graminis f. sp. hordei. This implies ~200
      million years of evolutionary conservation of the underlying immune mechanism. A
      time-course RNA-seq analysis in transgenic Arabidopsis lines detected sustained
      expression of a large MLA1-dependent gene cluster. This cluster is greatly
      enriched in genes known to respond to the fungal cell wall-derived microbe
      associated molecular pattern chitin. The MLA1-dependent sustained transcript
      accumulation could define a conserved function of the nuclear pool of MLA1
      detected in barley and Arabidopsis. We also found that MLA1-triggered immunity
      was fully retained in mutant plants that are simultaneously depleted of ethylene,
      jasmonic acid, and salicylic acid signaling. This points to the existence of an
      evolutionarily conserved and phytohormone-independent MLA1-mediated resistance
      mechanism. This also suggests a conserved mechanism for internalization of B.
      graminis f. sp. hordei effectors into host cells of flowering plants.
      Furthermore, the deduced connectivity of the NLR to multiple branches of immune
      signaling pathways likely confers increased robustness against pathogen effector
      mediated interception of host immune signaling and could have contributed to the
      evolutionary preservation of the immune mechanism.

PMID- 23175787
TI  - Tuning ion correlations at an electrified soft interface.
AB  - Ion distributions play a central role in various settings-from biology, where
      they mediate the electrostatic interactions between charged biomolecules in
      solution, to energy storage devices, where they influence the charging properties
      of supercapacitors. These distributions are determined by interactions dictated
      by the chemical properties of the ions and their environment as well as the long
      range nature of the electrostatic force. Recent theoretical and computational
      studies have explored the role of correlations between ions, which have been
      suggested to underlie a number of counterintuitive results, such as like-charge
      attraction. However, the interdependency between ion correlations and other
      interactions that ions experience in solution complicates the connection between
      physical models of ion correlations and the experimental investigation of ion
      distributions. We exploit the properties of the liquid/liquid interface to vary
      the coupling strength   of ion-ion correlations from weak to strong while
      monitoring their influence on ion distributions at the nanometer scale with X-ray
      reflectivity and the macroscopic scale with interfacial tension measurements.
      These data are in agreement with the predictions of a parameter-free density
      functional theory that includes ion-ion correlations and ion-solvent interactions
      over the entire range of experimentally tunable correlation coupling strengths
      (from 0.8 to 3.7). This study provides evidence for a sharply defined electrical
      double layer for large coupling strengths in contrast to the diffuse
      distributions predicted by mean field theory, thereby confirming a common
      prediction of many ion correlation models. The reported findings represent a
      significant advance in elucidating the nature and role of ion correlations in
      charged soft matter.

PMID- 23175788
TI  - Structural mechanism of ubiquitin and NEDD8 deamidation catalyzed by bacterial
      effectors that induce macrophage-specific apoptosis.
AB  - Targeting eukaryotic proteins for deamidation modification is increasingly
      appreciated as a general bacterial virulence mechanism. Here, we present an
      atomic view of how a bacterial deamidase effector, cycle-inhibiting factor
      homolog in Burkholderia pseudomallei (CHBP), recognizes its host targets,
      ubiquitin (Ub) and Ub-like neural precursor cell expressed, developmentally down
      regulated 8 (NEDD8), and catalyzes site-specific deamidation. Crystal structures
      of CHBP-Ub/NEDD8 complexes show that Ub and NEDD8 are similarly cradled by a
      large cleft in CHBP with four contacting surfaces. The pattern of Ub/NEDD8
      recognition by CHBP resembles that by the E1 activation enzyme, which critically
      involves the Lys-11 surface in Ub/NEDD8. Close examination of the papain-like
      catalytic center reveals structural determinants of CHBP being an obligate
      glutamine deamidase. Molecular-dynamics simulation identifies Gln-31/Glu-31 of
      Ub/NEDD8 as one key determinant of CHBP substrate preference for NEDD8. Inspired
      by the idea of using the unique bacterial activity as a tool, we further discover
      that CHBP-catalyzed NEDD8 deamidation triggers macrophage-specific apoptosis,
      which predicts a previously unknown macrophage-specific proapoptotic signal that
      is negatively regulated by neddylation-mediated protein
      ubiquitination/degradation.

PMID- 23175789
TI  - Preconfiguration of the antigen-binding site during affinity maturation of a
      broadly neutralizing influenza virus antibody.
AB  - Affinity maturation refines a naive B-cell response by selecting mutations in
      antibody variable domains that enhance antigen binding. We describe a B-cell
      lineage expressing broadly neutralizing influenza virus antibodies derived from a
      subject immunized with the 2007 trivalent vaccine. The lineage comprises three
      mature antibodies, the unmutated common ancestor, and a common intermediate.
      Their heavy-chain complementarity determining region inserts into the conserved
      receptor-binding pocket of influenza HA. We show by analysis of structures,
      binding kinetics and long time-scale molecular dynamics simulations that antibody
      evolution in this lineage has rigidified the initially flexible heavy-chain
      complementarity determining region by two nearly independent pathways and that
      this preconfiguration accounts for most of the affinity gain. The results advance
      our understanding of strategies for developing more broadly effective influenza
      vaccines.

PMID- 23175790
TI  - Multidrug binding properties of the AcrB efflux pump characterized by molecular
      dynamics simulations.
AB  - Multidrug resistance in Gram-negative bacteria, to which multidrug efflux pumps
      such as the AcrB transporter makes a major contribution, is becoming a major
      public health problem. Unfortunately only a few compounds have been
      cocrystallized with AcrB, and thus computational approaches are essential in
      elucidating the interaction between diverse ligands and the pump protein. We used
      molecular dynamics simulation to examine the binding of nine substrates, two
      inhibitors, and two nonsubstrates to the distal binding pocket of AcrB,
      identified earlier by X-ray crystallography. This approach gave us more realistic
      views of the binding than the previously used docking approach, as the explicit
      water molecules contributed to the process and the flexible binding site was
      often seen to undergo large structural changes. We analyzed the interaction in
      detail in terms of the binding energy, hydrophobic surface-matching, and the
      residues involved in the process. We found that all substrates tested bound to
      the pocket, whereas the binding to this site was not preferred for the
      nonsubstrates. Interestingly, both inhibitors [Phe-Arg-beta-naphthylamide and 1
      (1-naphtylmethyl)-piperazine] tended to move out of the pocket at least
      partially, getting into contact with a glycine-rich loop that separates the
      distal pocket from the more proximal region of the protein and is thought to
      control the access of substrates to the distal pocket.

PMID- 23175792
TI  - The agencies method for coalition formation in experimental games.
AB  - In society, power is often transferred to another person or group. A previous
      work studied the evolution of cooperation among robot players through a coalition
      formation game with a non-cooperative procedure of acceptance of an agency of
      another player. Motivated by this previous work, we conduct a laboratory
      experiment on finitely repeated three-person coalition formation games. Human
      players with different strength according to the coalition payoffs can accept a
      transfer of power to another player, the agent, who then distributes the
      coalition payoffs. We find that the agencies method for coalition formation is
      quite successful in promoting efficiency. However, the agent faces a tension
      between short-term incentives of not equally distributing the coalition payoff
      and the long-term concern to keep cooperation going. In a given round, the strong
      player in our experiment often resolves this tension approximately in line with
      the Shapley value and the nucleolus. Yet aggregated over all rounds, the payoff
      differences between players are rather small, and the equal division of payoffs
      predicts about 80% of all groups best. One reason is that the voting procedure
      appears to induce a balance of power, independent of the individual player's
      strength: Selfish subjects tend to be voted out of their agency and are further
      disciplined by reciprocal behaviors.

PMID- 23175791
TI  - Specific and reversible DNA-directed self-assembly of oil-in-water emulsion
      droplets.
AB  - Higher-order structures that originate from the specific and reversible DNA
      directed self-assembly of microscopic building blocks hold great promise for
      future technologies. Here, we functionalized biotinylated soft colloid oil-in
      water emulsion droplets with biotinylated single-stranded DNA oligonucleotides
      using streptavidin as an intermediary linker. We show the components of this
      modular linking system to be stable and to induce sequence-specific aggregation
      of binary mixtures of emulsion droplets. Three length scales were thereby
      involved: nanoscale DNA base pairing linking microscopic building blocks resulted
      in macroscopic aggregates visible to the naked eye. The aggregation process was
      reversible by changing the temperature and electrolyte concentration and by the
      addition of competing oligonucleotides. The system was reset and reused by
      subsequent refunctionalization of the emulsion droplets. DNA-directed self
      assembly of oil-in-water emulsion droplets, therefore, offers a solid basis for
      programmable and recyclable soft materials that undergo structural rearrangements
      on demand and that range in application from information technology to medicine.

PMID- 23175793
TI  - Using distance correlation and SS-ANOVA to assess associations of familial
      relationships, lifestyle factors, diseases, and mortality.
AB  - We present a method for examining mortality as it is seen to run in families, and
      lifestyle factors that are also seen to run in families, in a subpopulation of
      the Beaver Dam Eye Study. We observe that pairwise distance between death age in
      related persons is on average less than pairwise distance in death age between
      random pairs of unrelated persons. Our goal is to examine the hypothesis that
      pairwise differences in lifestyle factors correlate with the observed pairwise
      differences in death age that run in families. Szekely and Rizzo [Szekely GJ,
      Rizzo ML (2009) Ann Appl Stat 3(4): 1236-1265] have recently developed a method
      called distance correlation, which is suitable for this task with some
      enhancements. We build a Smoothing Spline ANOVA (SS-ANOVA) model for predicting
      death age based on four major lifestyle factors generally known to be related to
      mortality and four major diseases contributing to mortality, to develop a
      lifestyle mortality risk vector and a disease mortality risk vector. We then
      examine to what extent pairwise differences in these scores correlate with
      pairwise differences in mortality as they occur between family members and
      between unrelated persons. We find significant distance correlations between
      death ages, lifestyle factors, and family relationships. Considering only sib
      pairs compared with unrelated persons, distance correlation between siblings and
      mortality is, not surprisingly, stronger than that between more distantly related
      family members and mortality. The methodological approach here adapts to
      exploring relationships between multiple clusters of variables with observable
      (real-valued) attributes, and other factors for which only possibly nonmetric
      pairwise dissimilarities are observed.

PMID- 23175794
TI  - Individuals are inadequate: recognizing the family-centeredness of Chinese
      bioethics and Chinese health system.
AB  - This paper is aimed at a critical assessment of the moral framework of the
      current Chinese health system from a Confucian perspective, by focusing on the
      debate between the individual directed approach and the family-oriented approach
      to a health care system. Concerned with the nature and status of the family in
      communal life, the paper deals with the following questions: to cope with the
      frailties of material life (including susceptibility to disease), what good is
      presupposed by human existence and flourishing; why it is the family that serves
      as the primary locus of bearing and realizing this unique good; and what kind of
      society might possess the structures necessary to achieve the good thus
      conceived. All these questions lead to a revision of the theory of justice
      required in health care, in favor of family health saving accounts as an
      important institutional guarantee.

PMID- 23175795
TI  - Values and health care: the Confucian dimension in health care reform.
AB  - Are values and social priorities universal, or do they vary across geography,
      culture, and time? This question is very relevant to Asia's emerging economies
      that are increasingly looking at Western models for answers to their own outmoded
      health care systems that are in dire need of reform. But is it safe for them to
      do so without sufficient regard to their own social, political, and philosophical
      moorings? This article argues that historical and cultural legacies influence
      prevailing social values with regard to health care financing and resource
      allocation, and that the Confucian dimension provides a helpful entry point for a
      deeper understanding of ongoing health care reforms in East Asia--as exemplified
      by the unique case of Singapore.

PMID- 23175796
TI  - Modular exchange of substrate-binding loops alters both substrate and cofactor
      specificity in a member of the aldo-keto reductase superfamily.
AB  - Substrate specificity in the aldo-keto reductase (AKR) superfamily is determined
      by three mobile loops positioned at the top of the canonical (alpha/beta)(8)
      barrel structure. These loops have previously been demonstrated to be modular in
      a well-studied class of AKRs, in that exchanging loops between two similar
      hydroxysteroid dehydrogenases resulted in a complete alteration of substrate
      specificity (Ma,H. and Penning,T.M. (1999) Proc. Natl Acad. Sci. USA, 96, 11161
      11166). Here, we further examine the modularity of these loops by grafting those
      from human aldose reductase (hAR) into the hyperthermostable AKR, alcohol
      dehydrogenase D (AdhD), from Pyrococcus furiosus. Replacement of Loops A and B
      was sufficient to impart hAR activity into AdhD, and the resulting chimera
      retained the thermostability of the parent enzyme. However, no active chimeras
      were observed when the hAR loops were grafted into a previously engineered
      cofactor specificity mutant of AdhD, which displayed similar kinetics to hAR with
      the model substrate dl-glyceraldehyde. The non-additivity of these mutations
      suggests that efficient turnover is more dependent on the relative positioning of
      the cofactor and substrate in the active site than on binding of the individual
      species. The ability to impart the substrate specificities of mesostable AKRs
      into a thermostable scaffold will be useful in a variety of applications
      including immobilized enzyme systems for bioelectrocatalysis and fine chemical
      synthesis.

PMID- 23175797
TI  - A series of anti-CEA/anti-DOTA bispecific antibody formats evaluated for pre
      targeting: comparison of tumor uptake and blood clearance.
AB  - A series of anti-tumor/anti-chelate bispecific antibody formats were developed
      for pre-targeted radioimmunotherapy. Based on the anti-carcinoembryonic antigen
      humanized hT84.66-M5A monoclonal antibody and the anti-DOTA C8.2.5 scFv antibody
      fragment, this cognate series of bispecific antibodies were radioiodinated to
      determine their tumor targeting, biodistribution and pharmacokinetic properties
      in a mouse xenograft tumor model. The in vivo biodistribution studies showed that
      all the bispecific antibodies exhibited specific high tumor uptake but the tumor
      targeting was approximately one-half of the parental anti-CEA mAb due to faster
      blood clearance. Serum stability and FcRn studies showed no apparent reason for
      the faster blood clearance. A dual radiolabel biodistribution study revealed that
      the (111)In-DOTA bispecific antibody had increased liver and spleen uptake, not
      seen for the (125)I-version due to metabolism and release of the radioiodine from
      the cells. These data suggest increased clearance of the antibody fusion formats
      by the mononuclear phagocyte system. Importantly, a pre-targeted study showed
      specific tumor uptake of (177)Lu-DOTA and a tumor : blood ratio of 199 : 1. This
      pre-targeted radiotherapeutic and substantial reduction in the radioactive
      exposure to the bone marrow should enhance the therapeutic potential of RIT.

PMID- 23175799
TI  - Random walk of motor planning in task-irrelevant dimensions.
AB  - The movements that we make are variable. It is well established that at least a
      part of this variability is caused by noise in central motor planning. Here, we
      studied how the random effects of planning noise translate into changes in motor
      planning. Are the random effects independently added to a constant mean end
      point, or do they accumulate over movements? To distinguish between these
      possibilities, we examined repeated, discrete movements in various tasks in which
      the motor output could be decomposed into a task-relevant and a task-irrelevant
      component. We found in all tasks that the task-irrelevant component had a
      positive lag 1 autocorrelation, suggesting that the random effects of planning
      noise accumulate over movements. In contrast, the task-relevant component always
      had a lag 1 autocorrelation close to zero, which can be explained by effective
      trial-by-trial correction of motor planning on the basis of observed motor
      errors. Accumulation of the effects of planning noise is consistent with current
      insights into the stochastic nature of synaptic plasticity. It leads to motor
      exploration, which may subserve motor learning and performance optimization.

PMID- 23175798
TI  - Cortical effects of repetitive finger flexion- vs. extension-resisted tracking
      movements: a TMS study.
AB  - While the cortical effects of repetitive motor activity are generally believed to
      be task specific, the task parameters that modulate these effects are
      incompletely understood. Since there are differences in the neural control of
      flexor vs. extensor muscles, the type of muscles involved in the motor task of
      interest may be one important parameter. In addition, the role each muscle plays
      in the task, such as whether or not it is the prime mover, is another potentially
      important task parameter. In the present study, use-dependent cortical plasticity
      was examined in healthy volunteers performing a robotic waveform tracking task
      with either the extensor digitorum communis (EDC) or flexor digitorum
      superficialis (FDS) acting as the prime mover. Transcranial magnetic stimulation
      was used to measure corticospinal excitability (CE) and short-interval
      intracortical inhibition of lower and higher threshold corticospinal neurons
      (SICI(L) and SICI(H), respectively) before and after a flexion- or extension
      resisted finger tracking task. After repetitive performance of the tracking task,
      there was a significant decrease in SICI(L) targeting the EDC, while no change in
      CE targeting EDC was observed. In contrast, the reverse pattern was observed in
      the FDS: a significant increase in CE with no change in SICI(L). There was also a
      tendency toward increased SICI(H) targeting whichever muscle was acting as the
      prime mover, although this effect did not reach statistical significance. We
      conclude that there is a difference in patterns of use-dependent plasticity
      between extrinsic finger flexor and extensor muscles performing the same task.

PMID- 23175800
TI  - Responses to loud auditory stimuli indicate that movement-related activation
      builds up in anticipation of action.
AB  - Previous research using a loud acoustic stimulus (LAS) to investigate motor
      preparation in reaction time (RT) tasks indicates that responses can be triggered
      well in advance of the presentation of an imperative stimulus (IS). This is
      intriguing given that high levels of response preparation cannot be maintained
      for long periods (~ 200 ms). In the experiments reported here we sought to assess
      whether response-related activation increases gradually over time in simple RT
      tasks. In experiment 1, a LAS was presented at different times just prior to the
      presentation of the IS to probe the level of activation for the motor response.
      In experiment 2, the same LAS was presented at different times after the
      presentation of the IS. The results provide evidence that response-related
      activation does increase gradually in anticipation of the IS, but it remains
      stable for a short time after this event. The data display a pattern consistent
      with the response being triggering by the LAS, rather than a reaction to the IS.

PMID- 23175801
TI  - The role of envelope shape in the localization of multiple sound sources and
      echoes in the barn owl.
AB  - Echoes and sounds of independent origin often obscure sounds of interest, but
      echoes can go undetected under natural listening conditions, a perception called
      the precedence effect. How does the auditory system distinguish between echoes
      and independent sources? To investigate, we presented two broadband noises to
      barn owls (Tyto alba) while varying the similarity of the sounds' envelopes. The
      carriers of the noises were identical except for a 2- or 3-ms delay. Their onsets
      and offsets were also synchronized. In owls, sound localization is guided by
      neural activity on a topographic map of auditory space. When there are two
      sources concomitantly emitting sounds with overlapping amplitude spectra, space
      map neurons discharge when the stimulus in their receptive field is louder than
      the one outside it and when the averaged amplitudes of both sounds are rising. A
      model incorporating these features calculated the strengths of the two sources'
      representations on the map (B. S. Nelson and T. T. Takahashi; Neuron 67: 643-655,
      2010). The target localized by the owls could be predicted from the model's
      output. The model also explained why the echo is not localized at short delays:
      when envelopes are similar, peaks in the leading sound mask corresponding peaks
      in the echo, weakening the echo's space map representation. When the envelopes
      are dissimilar, there are few or no corresponding peaks, and the owl localizes
      whichever source is predicted by the model to be less masked. Thus the precedence
      effect in the owl is a by-product of a mechanism for representing multiple sound
      sources on its map.

PMID- 23175802
TI  - Characterization of respiratory neurons in the rostral ventrolateral medulla, an
      area critical for vocal production in songbirds.
AB  - Much is known about the neuronal cell types and circuitry of the mammalian
      respiratory brainstem and its role in normal, quiet breathing. Our understanding
      of the role of respiration in the context of vocal production, however, is very
      limited. Songbirds contain a well-defined neural circuit, known as the song
      system, which is necessary for song production and is strongly coupled to the
      respiratory system. A major target of this system is nucleus parambigualis (PAm)
      in the ventrolateral medulla, a structure that controls inspiration by way of its
      bulbospinal projections but is also an integral part of the song-pattern
      generation circuit by way of its "thalamocortical" projections to song-control
      nuclei in the telencephalon. We have mapped out PAm to characterize the cell
      types and its functional organization. Extracellular single units were obtained
      in anesthetized adult male zebra finches while measuring air sac pressure to
      monitor respiration. Single units were characterized by their discharge patterns
      and the phase of the activity in the respiratory cycle. Several classes of
      neurons were identified and were analogous to those reported for mammalian
      medullary respiratory neurons. The majority of the neurons in PAm was classified
      as inspiratory augmenting or preinspiratory, although other basic discharge
      patterns were observed as well. The well-characterized connectivity of PAm within
      the vocal motor circuit and the similarity of its neural firing patterns to the
      rostral ventral respiratory group and pre-Botzinger complex of mammals make it an
      ideal system for investigating the integration of breathing and vocalization.

PMID- 23175803
TI  - Variation in sodium current amplitude between vasopressin and oxytocin
      hypothalamic supraoptic neurons.
AB  - Biophysical characteristics of tetrodotoxin-sensitive sodium (Na(+)) currents
      were studied in vasopressin (VP) and oxytocin (OT) supraoptic neurons acutely
      isolated from rat hypothalamus. Na(+) current density (pA/pF) was significantly
      greater in VP neurons than in OT neurons. No significant difference between VP
      and OT neurons was detected regarding the voltage dependence of activation and
      steady-state inactivation, or rate of recovery from inactivation of Na(+)
      currents. In both VP and OT neurons, the macroscopic inactivation of the Na(+)
      currents was best fitted with a double-exponential expression suggesting two
      rates of inactivation. Also in both types, the time course of recovery from
      inactivation proceeded with fast and slow time constants averaging around 8 and
      350 ms, respectively, suggesting the presence of multiple pathways of recovery
      from inactivation. The slower time constant of recovery of inactivation may be
      involved in the decrease in action potential (AP) amplitude that occurs after the
      first spike during burst firing in both neuronal types. The larger amplitude of
      Na(+) currents in VP vs. OT neurons may explain the previous observations that VP
      neurons exhibit a lower AP threshold and greater AP amplitude than OT neurons,
      and may serve to differently tune the firing properties and responses to
      neuromodulators of the respective neuronal types.

PMID- 23175804
TI  - Directed functional connectivity matures with motor learning in a cortical
      pattern generator.
AB  - Sequential motor skills may be encoded by feedforward networks that consist of
      groups of neurons that fire in sequence (Abeles 1991; Long et al. 2010). However,
      there has been no evidence of an anatomic map of activation sequence in motor
      control circuits, which would be potentially detectable as directed functional
      connectivity of coactive neuron groups. The proposed pattern generator for
      birdsong, the HVC (Long and Fee 2008; Vu et al. 1994), contains axons that are
      preferentially oriented in the rostrocaudal axis (Nottebohm et al. 1982; Stauffer
      et al. 2012). We used four-tetrode recordings to assess the activity of ensembles
      of single neurons along the rostrocaudal HVC axis in anesthetized zebra finches.
      We found an axial, polarized neural network in which sequential activity is
      directionally organized along the rostrocaudal axis in adult males, who produce a
      stereotyped song. Principal neurons fired in rostrocaudal order and with
      interneurons that were rostral to them, suggesting that groups of excitatory
      neurons fire at the leading edge of travelling waves of inhibition. Consistent
      with the synchronization of neurons by caudally travelling waves of inhibition,
      the activity of interneurons was more coherent in the orthogonal mediolateral
      axis than in the rostrocaudal axis. If directed functional connectivity within
      the HVC is important for stereotyped, learned song, then it may be lacking in
      juveniles, which sing a highly variable song. Indeed, we found little evidence
      for network directionality in juveniles. These data indicate that a functionally
      directed network within the HVC matures during sensorimotor learning and may
      underlie vocal patterning.

PMID- 23175806
TI  - Coding of the long-term value of multiple future rewards in the primate striatum.
AB  - Decisions maximizing benefits involve a tradeoff between the quantity of a reward
      and the cost of elapsed time until an animal receives it. The estimation of long
      term reward values is critical to attain the most desirable outcomes over a
      certain period of time. Reinforcement learning theories have established
      algorithms to estimate the long-term reward values of multiple future rewards in
      which the values of future rewards are discounted as a function of how many steps
      of choices are necessary to achieve them. Here, we report that presumed striatal
      projection neurons represent the long-term values of multiple future rewards
      estimated by a standard reinforcement learning model while monkeys are engaged in
      a series of trial-and-error choices and adaptive decisions for multiple rewards.
      We found that the magnitude of activity of a subset of neurons was positively
      correlated with the long-term reward values, and that of another subset of
      neurons was negatively correlated throughout the entire decision-making process
      in individual trials: from the start of the task trial, estimation of the values
      and their comparison among alternatives, choice execution, and evaluation of the
      received rewards. An idiosyncratic finding was that neurons showing negative
      correlations represented reward values in the near future (high discounting),
      while neurons showing positive correlations represented reward values not only in
      the near future, but also in the far future (low discounting). These findings
      provide a new insight that long-term value signals are embedded in two subsets of
      striatal neurons as high and low discounting of multiple future rewards.

PMID- 23175805
TI  - Development of temporal structure in zebra finch song.
AB  - Zebra finch song has provided an excellent case study in the neural basis of
      sequence learning, with a high degree of temporal precision and tight links with
      precisely timed bursting in forebrain neurons. To examine the development of song
      timing, we measured the following four aspects of song temporal structure at four
      age ranges between 65 and 375 days posthatch: the mean durations of song
      syllables and the silent gaps between them, timing variability linked to song
      tempo, timing variability expressed independently across syllables and gaps, and
      transition probabilities between consecutive syllable pairs. We found substantial
      increases in song tempo between 65 and 85 days posthatch, due almost entirely to
      a shortening of gaps. We also found a decrease in tempo variability, also
      specific to gaps. Both the magnitude of the increase in tempo and the decrease in
      tempo variability were correlated on gap-by-gap basis with increases in the
      reliability of corresponding syllable transitions. Syllables had no systematic
      increase in tempo or decrease in tempo variability. In contrast to tempo
      parameters, both syllables and gaps showed an early sharp reduction in
      independent variability followed by continued reductions over the first year. The
      data suggest that links between syllable-based representations are strengthened
      during the later parts of the traditional period of song learning and that song
      rhythm continues to become more regular throughout the first year of life.
      Similar learning patterns have been identified in human sequence learning,
      suggesting a potentially rich area of comparative research.

PMID- 23175807
TI  - Does a basic deficit in force control underlie cerebellar ataxia?
AB  - Because damage to the cerebellum results in characteristic movement
      incoordination known as "ataxia," it has been hypothesized that it is involved in
      estimation of limb dynamics that occur during movement. However, cerebellar
      function may extend beyond movement to force control in general, with or without
      movement. Here we tested whether the cerebellum is involved in controlling force
      separate from estimating limb dynamics and whether ataxia could result from a
      deficit in force control. We studied patients with cerebellar ataxia controlling
      their arm force isometrically; in this condition arm dynamics are absent and
      there is no need for (or effect from an impairment in) estimations of limb
      dynamics. Subjects were required to control their force magnitude, direction, or
      both. Cerebellar patients were able to match force magnitude or direction
      similarly to control subjects. Furthermore, when controlling force magnitude,
      they intuitively chose directions (not specified) that required minimal effort at
      the joint level--this ability was also similar to control subjects. In contrast,
      cerebellar patients performed significantly worse than control subjects when
      asked to match both force magnitude and direction. This was surprising, since
      they did not exhibit significant impairment in doing either in isolation. These
      results show that cerebellum-dependent computations are not limited to
      estimations of body dynamics needed for active movement. Deficits occur even in
      isometric conditions, but apparently only when multiple degrees of freedom must
      be controlled simultaneously. Thus a fundamental cerebellar operation may be
      combining/coordinating degrees of freedom across many kinds of movements and
      behaviors.

PMID- 23175809
TI  - Target enhancement and distractor suppression in naturalistic visual search.

PMID- 23175808
TI  - Prospective study of family history and colorectal cancer risk by tumor LINE-1
      methylation level.
AB  - BACKGROUND: Beyond known familial colorectal cancer (CRC) syndromes, the
      mechanisms underlying the elevated CRC risk associated with CRC family history
      remain largely unknown. A recent retrospective study suggests familial clustering
      of CRC with hypomethylation in long interspersed nucleotide element 1 (LINE-1).
      We tested the hypothesis that CRC family history might confer a higher risk of
      LINE-1 methylation-low CRC. METHODS: Using the Nurses' Health Study and the
      Health Professionals Follow-up Study, we prospectively examined the association
      between CRC family history and the risk of rectal and colon cancer (N = 1224)
      according to tumor LINE-1 methylation level by duplication method Cox
      proportional hazards regression. We examined microsatellite instability (MSI)
      status to exclude the influence of Lynch syndrome. All statistical tests were two
      sided. RESULTS: The association between CRC family history and non-MSI CRC risk
      differed statistically significantly by LINE-1 methylation level (P
      (heterogeneity) = .02). CRC family history was associated with a statistically
      significantly higher risk of LINE-1 methylation-low non-MSI cancer (multivariable
      hazard ratio [HR] = 1.68, 95% confidence interval [CI] = 1.19 to 2.38 for 1 vs 0
      first-degree relatives with CRC; multivariable HR = 3.48, 95% CI = 1.59 to 7.6
      for >=2 vs 0 first-degree relatives with CRC; P (trend) < .001). In contrast, CRC
      family history was not statistically significantly associated with LINE-1
      methylation-high non-MSI cancer (P (trend) = .35). CONCLUSIONS: This molecular
      pathological epidemiology study shows that CRC family history is associated with
      a higher risk of LINE-1 methylation-low CRC, suggesting previously unrecognized
      heritable predisposition to epigenetic alterations. Additional studies are needed
      to evaluate tumor LINE-1 methylation as a molecular biomarker for familial cancer
      risk assessment.

PMID- 23175810
TI  - Levodopa-induced dyskinesia is strongly associated with resonant cortical
      oscillations.
AB  - The standard pharmacological treatment for Parkinson's disease using the dopamine
      precursor levodopa is unfortunately limited by gradual development of disabling
      involuntary movements for which the underlying causes are poorly understood. Here
      we show that levodopa-induced dyskinesia in hemiparkinsonian rats is strongly
      associated with pronounced 80 Hz local field potential oscillations in the
      primary motor cortex following levodopa treatment. When this oscillation is
      interrupted by application of a dopamine antagonist onto the cortical surface the
      dyskinetic symptoms disappear. The finding that abnormal cortical oscillations
      are a key pathophysiological mechanism calls for a revision of the prevailing
      hypothesis that links levodopa-induced dyskinesia to an altered sensitivity to
      dopamine only in the striatum. Apart from having important implications for the
      treatment of Parkinson's disease, the discovered pathophysiological mechanism may
      also play a role in several other psychiatric and neurological conditions
      involving cortical dysfunction.

PMID- 23175811
TI  - Enhanced GABAergic activity in the mouse primary somatosensory cortex is
      insufficient to alleviate chronic pain behavior with reduced expression of
      neuronal potassium-chloride cotransporter.
AB  - The correct balance between excitation and inhibition is crucial for brain
      function and disrupted in several pathological conditions. Excitatory neuronal
      circuits in the primary somatosensory cortex (S1) are modulated by local
      inhibitory neurons with the balance of this excitatory and inhibitory activity
      important for function. The activity of excitatory layer 2/3 neurons (L2/3) in
      the S1 cortex is increased in chronic pain, but it is not known how the local
      interneurons, nor the balance between excitation and inhibition, may change in
      chronic pain. Using in vivo two-photon calcium imaging and electrophysiology, we
      report here that the response of L2/3 local inhibitory neurons to both sensory
      stimulation and to layer 4 electrical stimulation increases in inflammatory
      chronic pain. Local application into L2/3 of a GABA(A) receptor blocker further
      enhanced the activity of S1 excitatory neurons and reduced pain thresholds,
      whereas local application of the GABA(A) receptor modulators (muscimol and
      diazepam) transiently alleviated the allodynia. This illustrates the importance
      of the local inhibitory pathways in chronic pain sensation. A reduction in the
      expression and function of the potassium-chloride cotransporter 2 occurred during
      chronic pain, which reduces the efficacy of the inhibitory inputs to L2/3
      excitatory neurons. In summary, both excitatory and inhibitory neuronal
      activities in the S1 are enhanced in the chronic pain model, but the increased
      inhibition is insufficient to completely counterbalance the increased excitation
      and alleviate the symptoms of chronic pain.

PMID- 23175812
TI  - An early onset progressive motor neuron disorder in Scyl1-deficient mice is
      associated with mislocalization of TDP-43.
AB  - The molecular and cellular bases of motor neuron diseases (MNDs) are still poorly
      understood. The diseases are mostly sporadic, with ~10% of cases being familial.
      In most cases of familial motor neuronopathy, the disease is caused by either
      gain-of-adverse-effect mutations or partial loss-of-function mutations in
      ubiquitously expressed genes that serve essential cellular functions. Here we
      show that deletion of Scyl1, an evolutionarily conserved and ubiquitously
      expressed gene encoding the COPI-associated protein pseudokinase SCYL1, causes an
      early onset progressive MND with characteristic features of amyotrophic lateral
      sclerosis (ALS). Skeletal muscles of Scyl1(-/-) mice displayed neurogenic
      atrophy, fiber type switching, and disuse atrophy. Peripheral nerves showed
      axonal degeneration. Loss of lower motor neurons (LMNs) and large-caliber axons
      was conspicuous in Scyl1(-/-) animals. Signs of neuroinflammation were seen
      throughout the CNS, most notably in the ventral horn of the spinal cord. Neural
      specific, but not skeletal muscle-specific, deletion of Scyl1 was sufficient to
      cause motor dysfunction, indicating that SCYL1 acts in a neural cell-autonomous
      manner to prevent LMN degeneration and motor functions. Remarkably, deletion of
      Scyl1 resulted in the mislocalization and accumulation of TDP-43 (TAR DNA-binding
      protein of 43 kDa) and ubiquilin 2 into cytoplasmic inclusions within LMNs,
      features characteristic of most familial and sporadic forms of ALS. Together, our
      results identify SCYL1 as a key regulator of motor neuron survival, and Scyl1(-/
      ) mice share pathological features with many human neurodegenerative conditions.

PMID- 23175813
TI  - RIM controls homeostatic plasticity through modulation of the readily-releasable
      vesicle pool.
AB  - Rab3 interacting molecules (RIMs) are evolutionarily conserved scaffolding
      proteins that are located at presynaptic active zones. In the mammalian nervous
      system, RIMs have two major activities that contribute to the fidelity of
      baseline synaptic transmission: they concentrate calcium channels at the active
      zone and facilitate synaptic vesicle docking/priming. Here we confirm that RIM
      has an evolutionarily conserved function at the Drosophila neuromuscular junction
      and then define a novel role for RIM during homeostatic synaptic plasticity. We
      show that loss of RIM disrupts baseline vesicle release, diminishes presynaptic
      calcium influx, and diminishes the size of the readily-releasable pool (RRP) of
      synaptic vesicles, consistent with known activities of RIM. However, loss of RIM
      also completely blocks the homeostatic enhancement of presynaptic
      neurotransmitter release that normally occurs after inhibition of postsynaptic
      glutamate receptors, a process termed synaptic homeostasis. It is established
      that synaptic homeostasis requires enhanced presynaptic calcium influx as a
      mechanism to potentiate vesicle release. However, despite a defect in baseline
      calcium influx in rim mutants, the homeostatic modulation of calcium influx
      proceeds normally. Synaptic homeostasis is also correlated with an increase in
      the size of the RRP of synaptic vesicles, although the mechanism remains unknown.
      Here we demonstrate that the homeostatic modulation of the RRP is blocked in the
      rim mutant background. Therefore, RIM-dependent modulation of the RRP is a
      required step during homeostatic plasticity. By extension, homeostatic plasticity
      appears to require two genetically separable processes, the enhancement of
      presynaptic calcium influx and a RIM-dependent modulation of the RRP.

PMID- 23175814
TI  - RIM promotes calcium channel accumulation at active zones of the Drosophila
      neuromuscular junction.
AB  - Synaptic communication requires the controlled release of synaptic vesicles from
      presynaptic axon terminals. Release efficacy is regulated by the many proteins
      that comprise the presynaptic release apparatus, including Ca(2+) channels and
      proteins that influence Ca(2+) channel accumulation at release sites. Here we
      identify Drosophila RIM (Rab3 interacting molecule) and demonstrate that it
      localizes to active zones at the larval neuromuscular junction. In Drosophila RIM
      mutants, there is a large decrease in evoked synaptic transmission because of a
      significant reduction in both the clustering of Ca(2+) channels and the size of
      the readily releasable pool of synaptic vesicles at active zones. Hence, RIM
      plays an evolutionarily conserved role in regulating synaptic calcium channel
      localization and readily releasable pool size. Because RIM has traditionally been
      studied as an effector of Rab3 function, we investigate whether RIM is involved
      in the newly identified function of Rab3 in the distribution of presynaptic
      release machinery components across release sites. Bruchpilot (Brp), an essential
      component of the active zone cytomatrix T bar, is unaffected by RIM disruption,
      indicating that Brp localization and distribution across active zones does not
      require wild-type RIM. In addition, larvae containing mutations in both RIM and
      rab3 have reduced Ca(2+) channel levels and a Brp distribution that is very
      similar to that of the rab3 single mutant, indicating that RIM functions to
      regulate Ca(2+) channel accumulation but is not a Rab3 effector for release
      machinery distribution across release sites.

PMID- 23175815
TI  - An effect of bilingualism on the auditory cortex.
AB  - Two studies (Golestani et al., 2007; Wong et al., 2008) have reported a positive
      correlation between the ability to perceive foreign speech sounds and the volume
      of Heschl's gyrus (HG), the structure that houses the auditory cortex. More
      precisely, participants with larger left Heschl's gyri learned consonantal or
      tonal contrasts faster than those with smaller HG. These studies leave open the
      question of the impact of experience on HG volumes. In the current research, we
      investigated the effect of early language exposure on Heschl's gyrus by comparing
      Spanish-Catalan bilinguals who have been exposed to two languages since
      childhood, to a group of Spanish monolinguals matched in education, socio
      economic status, and musical experience. Manual volumetric measurements of HG
      revealed that bilinguals have, on average, larger Heschl's gyri than
      monolinguals. This was corroborated, for the left Heschl's gyrus, by a voxel
      based morphometry analysis showing larger gray matter volumes in bilinguals than
      in monolinguals. Since the bilinguals in this study were not a self-selected
      group, this observation provides a clear demonstration that learning a second
      language is a causal factor in the increased size of the auditory cortex.

PMID- 23175816
TI  - Contribution of cholinergic and GABAergic mechanisms to direction tuning,
      discriminability, response reliability, and neuronal rate correlations in macaque
      middle temporal area.
AB  - Previous studies have investigated the effects of acetylcholine (ACh) on neuronal
      tuning, coding, and attention in primary visual cortex, but its contribution to
      coding in extrastriate cortex is unexplored. Here we investigate the effects of
      ACh on tuning properties of macaque middle temporal area MT neurons and contrast
      them with effects of gabazine, a GABA(A) receptor blocker. ACh increased neuronal
      activity, it had no effect on tuning width, but it significantly increased the
      direction discriminability of a neuron. Gabazine equally increased neuronal
      activity, but it widened tuning curves and decreased the direction
      discriminability of a neuron. Although gabazine significantly reduced response
      reliability, ACh application had little effect on response reliability. Finally,
      gabazine increased noise correlation of simultaneously recorded neurons, whereas
      ACh reduced it. Thus, both drugs increased firing rates, but only ACh application
      improved neuronal tuning and coding in line with effects seen in studies in which
      attention was selectively manipulated.

PMID- 23175817
TI  - Direct alteration of a specific inhibitory circuit of the hippocampus by
      antidepressants.
AB  - Correct brain functioning relies on the precise activity of a myriad of synapses
      assembling neurons in complex networks. In the hippocampus, highly diverse
      inhibitory circuits differently govern several physiologically relevant network
      activities. Particularly, perisomatic inhibition provided by specific
      interneurons was proposed to control emotional states, and could therefore be
      affected by mood disorders and their therapy. We found that both chronic and
      acute administration of two major antidepressants, imipramine and fluoxetine,
      strongly and directly altered GABA-mediated (GABAergic) hippocampal
      neurotransmission in mice and rats, independently of their effects on amine
      reuptake systems. These drugs affected GABA release from synapses formed by fast
      spiking cells, but not interneurons expressing cannabinoid receptor type 1,
      resulting in the disruption of gamma oscillations. This differential effect,
      shared by two types of antidepressants, suggests a new mechanism of action of
      these medications, and a possible role of perisomatic inhibition in depressive
      disorders.

PMID- 23175818
TI  - Sight and sound converge to form modality-invariant representations in
      temporoparietal cortex.
AB  - People can identify objects in the environment with remarkable accuracy,
      regardless of the sensory modality they use to perceive them. This suggests that
      information from different sensory channels converges somewhere in the brain to
      form modality-invariant representations, i.e., representations that reflect an
      object independently of the modality through which it has been apprehended. In
      this functional magnetic resonance imaging study of human subjects, we first
      identified brain areas that responded to both visual and auditory stimuli and
      then used crossmodal multivariate pattern analysis to evaluate the neural
      representations in these regions for content specificity (i.e., do different
      objects evoke different representations?) and modality invariance (i.e., do the
      sight and the sound of the same object evoke a similar representation?). While
      several areas became activated in response to both auditory and visual
      stimulation, only the neural patterns recorded in a region around the posterior
      part of the superior temporal sulcus displayed both content specificity and
      modality invariance. This region thus appears to play an important role in our
      ability to recognize objects in our surroundings through multiple sensory
      channels and to process them at a supramodal (i.e., conceptual) level.

PMID- 23175819
TI  - DSCAM contributes to dendrite arborization and spine formation in the developing
      cerebral cortex.
AB  - Down syndrome cell adhesion molecule, or DSCAM, has been implicated in many
      neurodevelopmental processes including axon guidance, dendrite arborization, and
      synapse formation. Here we show that DSCAM plays an important role in regulating
      the morphogenesis of cortical pyramidal neurons in the mouse. We report that
      DSCAM expression is developmentally regulated and localizes to synaptic plasma
      membranes during a time of robust cortical dendrite arborization and spine
      formation. Analysis of mice that carry a spontaneous mutation in DSCAM
      (DSCAM(del17)) revealed gross morphological changes in brain size and shape in
      addition to subtle changes in cortical organization, volume, and lamination.
      Early postnatal mutant mice displayed a transient decrease in cortical thickness,
      but these reductions could not be attributed to changes in neuron production or
      cell death. DSCAM(del17) mutants showed temporary impairments in the branching of
      layer V pyramidal neuron dendrites at P10 and P17 that recovered to normal by
      adulthood. Defects in DSCAM(del17) dendrite branching correlated with a temporal
      increase in apical branch spine density and lasting changes in spine morphology.
      At P15 and P42, mutant mice displayed a decrease in the percentage of large,
      stable spines and an increase in the percentage of small, immature spines.
      Together, our findings suggest that DSCAM contributes to pyramidal neuron
      morphogenesis by regulating dendrite arborization and spine formation during
      cortical circuit development.

PMID- 23175820
TI  - The CB(1) cannabinoid receptor drives corticospinal motor neuron differentiation
      through the Ctip2/Satb2 transcriptional regulation axis.
AB  - The generation and specification of pyramidal neuron subpopulations during
      development relies on a complex network of transcription factors. The CB(1)
      cannabinoid receptor is the major molecular target of endocannabinoids and
      marijuana active compounds. This receptor has been shown to influence neural
      progenitor proliferation and axonal growth, but its involvement in neuronal
      differentiation and the functional impact in the adulthood caused by altering its
      signaling during brain development are not known. Here we show that the CB(1)
      receptor, by preventing Satb2 (special AT-rich binding protein 2)-mediated
      repression, increased Ctip2 (COUP-TF interacting protein 2) promoter activity,
      and Ctip2-positive neuron generation. Unbalanced neurogenic fate determination
      found in complete CB(1)(-/-) mice and in glutamatergic neuron-specific Nex-CB(1)(
      /-) mice induced overt alterations in corticospinal motor neuron generation and
      subcerebral connectivity, thereby resulting in an impairment of skilled motor
      function in adult mice. Likewise, genetic deletion of CB(1) receptors in Thy1-YFP
      H mice elicited alterations in corticospinal tract development. Altogether, these
      data demonstrate that the CB(1) receptor contributes to the generation of deep
      layer cortical neurons by coupling endocannabinoid signals from the neurogenic
      niche to the intrinsic proneurogenic Ctip2/Satb2 axis, thus influencing
      appropriate subcerebral projection neuron specification and corticospinal motor
      function in the adulthood.

PMID- 23175822
TI  - Neural correlates of anticipation risk reflect risk preferences.
AB  - Individual risk preferences have a large influence on decisions, such as
      financial investments, career and health choices, or gambling. Decision making
      under risk has been studied both behaviorally and on a neural level. It remains
      unclear, however, how risk attitudes are encoded and integrated with choice.
      Here, we investigate how risk preferences are reflected in neural regions known
      to process risk. We collected functional magnetic resonance images of 56 human
      subjects during a gambling task (Preuschoff et al., 2006). Subjects were grouped
      into risk averters and risk seekers according to the risk preferences they
      revealed in a separate lottery task. We found that during the anticipation of
      high-risk gambles, risk averters show stronger responses in ventral striatum and
      anterior insula compared to risk seekers. In addition, risk prediction error
      signals in anterior insula, inferior frontal gyrus, and anterior cingulate
      indicate that risk averters do not dissociate properly between gambles that are
      more or less risky than expected. We suggest this may result in a general
      overestimation of prospective risk and lead to risk avoidance behavior. This is
      the first study to show that behavioral risk preferences are reflected in the
      passive evaluation of risky situations. The results have implications on public
      policies in the financial and health domain.

PMID- 23175823
TI  - Hippocampal phase precession from dual input components.
AB  - Phase precession is a well known phenomenon in which a hippocampal place cell
      will fire action potentials at successively earlier phases (relative to the theta
      band oscillations recorded in the local field potential) as an animal moves
      through the cell's receptive field (also known as a place field). We present a
      model in which CA1 pyramidal cell spiking is driven by dual input components
      arising from CA3 and EC3. The receptive fields of these two input components
      overlap but are offset in space from each other such that as the animal moves
      through the model place field, action potentials are driven first by the CA3
      input component and then the EC3 input component. As CA3 synaptic input is known
      to arrive in CA1 at a later theta phase than EC3 input (Mizuseki et al., 2009;
      Montgomery et al., 2009), CA1 spiking advances in phase as the model transitions
      from CA3-driven spiking to EC3-driven spiking. Here spike phase is a function of
      animal location, placing our results in agreement with many experimental
      observations characterizing CA1 phase precession (O'Keefe and Recce, 1993; Huxter
      et al., 2003; Geisler et al., 2007). We predict that experimental manipulations
      that dramatically enhance or disrupt activity in either of these areas should
      have a significant effect on phase precession observed in CA1.

PMID- 23175821
TI  - Precedence of the eye region in neural processing of faces.
AB  - Functional magnetic resonance imaging (fMRI) has revealed multiple subregions in
      monkey inferior temporal cortex (IT) that are selective for images of faces over
      other objects. The earliest of these subregions, the posterior lateral face patch
      (PL), has not been studied previously at the neurophysiological level. Perhaps
      not surprisingly, we found that PL contains a high concentration of "face
      selective" cells when tested with standard image sets comparable to those used
      previously to define the region at the level of fMRI. However, we here report
      that several different image sets and analytical approaches converge to show that
      nearly all face-selective PL cells are driven by the presence of a single eye in
      the context of a face outline. Most strikingly, images containing only an eye,
      even when incorrectly positioned in an outline, drove neurons nearly as well as
      full-face images, and face images lacking only this feature led to longer latency
      responses. Thus, bottom-up face processing is relatively local and linearly
      integrates features-consistent with parts-based models-grounding investigation of
      how the presence of a face is first inferred in the IT face processing hierarchy.

PMID- 23175824
TI  - Dopamine precursor depletion impairs timing in healthy volunteers by attenuating
      activity in putamen and supplementary motor area.
AB  - Neuropsychological investigations of patients with Parkinson's disease,
      schizophrenia, or attention deficit disorder converge with psychopharmacological
      studies in animals and healthy volunteers to implicate dopamine (DA) pathways in
      timing. In parallel, single-cell recording and functional neuroimaging studies
      have highlighted the importance of basal ganglia, prefrontal cortex, and
      supplementary motor area (SMA) for timing. In a placebo-controlled, within
      subject design, we combined event-related functional magnetic resonance imaging
      with a DA manipulation (acute phenylalanine/tyrosine depletion; APTD) in healthy
      volunteers to pinpoint the neuroanatomical and functional substrates of the DA
      modulation of timing. Behaviorally, APTD selectively impaired accuracy of
      perceptual timing, with no effect on performance of a color-control task matched
      for difficulty, working memory (WM), and attentional demands. Neurally, APTD
      attenuated timing-specific activity in the putamen and SMA. Notably, APTD-induced
      decreases in brain activity were directly correlated to APTD-induced impairments
      in timing performance. Moreover, APTD modulated timing-specific activity
      selectively during initial storage of the sample duration, but had no effect
      during its subsequent retrieval or comparison to a probe. Our results do not
      simply reflect DA modulation of WM since the color task controlled for the WM
      updating process necessary for timing of durations in the seconds range.
      Moreover, preliminary evidence indicated APTD effects on putamen and SMA were
      greater for subsecond (540 ms) than suprasecond (1080 ms) durations, when WM
      demands would actually be lower. Instead, we show for the first time in healthy
      humans that DA manipulation perturbs timing by attenuating the activity in
      putamen and SMA that mediates initial storage of temporal information into WM.

PMID- 23175825
TI  - Perceptual criteria in the human brain.
AB  - A critical component of decision making is the ability to adjust criteria for
      classifying stimuli. fMRI and drift diffusion models were used to explore the
      neural representations of perceptual criteria in decision making. The specific
      focus was on the relative engagement of perceptual- and decision-related neural
      systems in response to adjustments in perceptual criteria. Human participants
      classified visual stimuli as big or small based on criteria of different sizes,
      which effectively biased their choices toward one response over the other. A
      drift diffusion model was fit to the behavioral data to extract estimates of
      stimulus size, criterion size, and difficulty for each participant and condition.
      These parameter values were used as modulated regressors to create a highly
      constrained model for the fMRI analysis that accounted for several components of
      the decision process. The results show that perceptual criteria values were
      reflected by activity in left inferior temporal cortex, a region known to
      represent objects and their physical properties, whereas stimulus size was
      reflected by activation in occipital cortex. A frontoparietal network of regions,
      including dorsolateral prefrontal cortex and superior parietal lobule,
      corresponded to the decision variables resulting from the downstream stimulus
      criterion comparison, independent of stimulus type. The results provide novel
      evidence that perceptual criteria are represented in stimulus space and serve as
      inputs to be compared with the presented stimulus, recruiting a common network of
      decision regions shown to be active in other simple decisions. This work advances
      our understanding of the neural correlates of decision flexibility and
      adjustments of behavioral bias.

PMID- 23175827
TI  - Chronic intermittent hypoxia depresses afferent neurotransmission in NTS neurons
      by a reduction in the number of active synapses.
AB  - Long-term synaptic plasticity has been recently described in brainstem areas
      associated to visceral afferent sensory integration. Chronic intermittent hypoxia
      (CIH), an animal model for studying obstructive sleep apnea in humans, depresses
      the afferent neurotransmission in nucleus tractus solitarii (NTS) neurons, which
      affect respiratory and autonomic regulation. Here we identified the synaptic
      mechanisms of CIH-induced depression of the afferent neurotransmission in NTS
      neurons in juvenile rats. We verified that CIH reduced the amplitude of both NMDA
      and non-NMDA glutamatergic excitatory currents (eEPSCs) evoked by tractus
      solitarii stimulation (TS-eEPSC) of second-order neurons in the NTS. No changes
      were observed in release probability, evidenced by absence of any CIH-elicited
      effects on short-term depression and failures in EPSCs evoked in low calcium. CIH
      also produced no changes in TS-eEPSC quantal size, since the amplitudes of both
      low calcium-evoked EPSCs and asynchronous TS-eEPSCs (evoked in the presence of
      Sr(2+)) were unchanged. Using single TS afferent fiber stimulation in slices from
      control and CIH rats we clearly show that CIH reduced the quantal content of the
      TS-eEPSCs without affecting the quantal size or release probability, suggesting a
      reduction in the number of active synapses as the mechanism of CIH induced TS
      eEPSC depression. In accordance with this concept, the input-output relationship
      of stimulus intensity and TS-eEPSC amplitude shows an early saturation in CIH
      animals. These findings open new perspectives for a better understanding of the
      mechanisms underlying the synaptic plasticity in the brainstem sensory neurons
      under challenges such as those produced by CIH in experimental and pathological
      conditions.

PMID- 23175826
TI  - Cognitive enhancement with rosiglitazone links the hippocampal PPARgamma and ERK
      MAPK signaling pathways.
AB  - We previously reported that the peroxisome proliferator-activated receptor gamma
      (PPARgamma) agonist rosiglitazone (RSG) improved hippocampus-dependent cognition
      in the Alzheimer's disease (AD) mouse model, Tg2576. RSG had no effect on wild
      type littermate cognitive performance. Since extracellular signal-regulated
      protein kinase mitogen-activated protein kinase (ERK MAPK) is required for many
      forms of learning and memory that are affected in AD, and since both PPARgamma
      and ERK MAPK are key mediators of insulin signaling, the current study tested the
      hypothesis that RSG-mediated cognitive improvement induces a hippocampal
      PPARgamma pattern of gene and protein expression that converges with the ERK MAPK
      signaling axis in Tg2576 AD mice. In the hippocampal PPARgamma transcriptome, we
      found significant overlap between peroxisome proliferator response element
      containing PPARgamma target genes and ERK-regulated, cAMP response element
      containing target genes. Within the Tg2576 dentate gyrus proteome, RSG induced
      proteins with structural, energy, biosynthesis and plasticity functions. Several
      of these proteins are known to be important for cognitive function and are also
      regulated by ERK MAPK. In addition, we found the RSG-mediated augmentation of
      PPARgamma and ERK2 activity during Tg2576 cognitive enhancement was reversed when
      hippocampal PPARgamma was pharmacologically antagonized, revealing a coordinate
      relationship between PPARgamma transcriptional competency and phosphorylated ERK
      that is reciprocally affected in response to chronic activation, compared with
      acute inhibition, of PPARgamma. We conclude that the hippocampal transcriptome
      and proteome induced by cognitive enhancement with RSG harnesses a dysregulated
      ERK MAPK signal transduction pathway to overcome AD-like cognitive deficits in
      Tg2576 mice. Thus, PPARgamma represents a signaling system that is not crucial
      for normal cognition yet can intercede to restore neural networks compromised by
      AD.

PMID- 23175828
TI  - Perceptual learning selectively refines orientation representations in early
      visual cortex.
AB  - Although practice has long been known to improve perceptual performance, the
      neural basis of this improvement in humans remains unclear. Using fMRI in
      conjunction with a novel signal detection-based analysis, we show that extensive
      practice selectively enhances the neural representation of trained orientations
      in the human visual cortex. Twelve observers practiced discriminating small
      changes in the orientation of a laterally presented grating over 20 or more daily
      1 h training sessions. Training on average led to a twofold improvement in
      discrimination sensitivity, specific to the trained orientation and the trained
      location, with minimal improvement found for untrained orthogonal orientations or
      for orientations presented in the untrained hemifield. We measured the strength
      of orientation-selective responses in individual voxels in early visual areas (V1
      V4) using signal detection measures, both before and after training. Although the
      overall amplitude of the BOLD response was no greater after training, practice
      nonetheless specifically enhanced the neural representation of the trained
      orientation at the trained location. This training-specific enhancement of
      orientation-selective responses was observed in the primary visual cortex (V1) as
      well as higher extrastriate visual areas V2-V4, and moreover, reliably predicted
      individual differences in the behavioral effects of perceptual learning. These
      results demonstrate that extensive training can lead to targeted functional
      reorganization of the human visual cortex, refining the cortical representation
      of behaviorally relevant information.

PMID- 23175830
TI  - The lateral hypothalamic area controls paradoxical (REM) sleep by means of
      descending projections to brainstem GABAergic neurons.
AB  - It has recently been shown that the ventrolateral part of the periaqueductal gray
      (VLPAG) and the adjacent dorsal deep mesencephalic nucleus (dDpMe) contain
      GABAergic neurons gating paradoxical sleep (PS) onset by means of their
      projection to the glutamatergic PS-on neurons of the sublaterodorsal tegmental
      nucleus (SLD). To determine the mechanisms responsible for the cessation of
      activity of these GABAergic PS-off neurons at the onset and during PS, we
      combined the immunostaining of c-FOS, a marker of neuronal activation, with
      cholera toxin b subunit (CTb) retrograde tracing from the VLPAG/dDpMe in three
      groups of rats (control, PS deprived, and PS hypersomniac). We found that the
      lateral hypothalamic area (LH) is the only brain structure containing a very
      large number of neurons activated during PS hypersomnia and projecting to the
      VLPAG/dDpMe. We further demonstrated that 44% of these neurons express the
      neuropeptide melanin concentrating hormone (MCH). We then showed that bilateral
      injections in the LH of two inhibitory compounds, clonidine (an alpha-2
      adrenergic agonist) and muscimol (a GABAa agonist) induce an inhibition of PS.
      Furthermore, after muscimol injections in the LH, the VLPAG/dDpMe contained a
      large number of activated neurons, mostly GABAergic, and projecting to the SLD.
      Altogether, our results indicate for the first time that the activation of a
      population of LH neurons, in part MCH containing, is necessary for PS to occur.
      Furthermore, our results strongly suggest that these neurons trigger PS by means
      of their inhibitory projection to the PS-off GABAergic neurons located in the
      VLPAG/dDpMe.

PMID- 23175829
TI  - NMDA receptor-dependent afterdepolarizations are curtailed by carbonic anhydrase
      14: regulation of a short-term postsynaptic potentiation.
AB  - In the hippocampus, extracellular carbonic anhydrase (Car) speeds the buffering
      of an activity-generated rise in extracellular pH that impacts H(+)-sensitive
      NMDA receptors (NMDARs). We studied the role of Car14 in this brain structure, in
      which it is expressed solely on neurons. Current-clamp responses were recorded
      from CA1 pyramidal neurons in wild-type (WT) versus Car14 knock-out (KO) mice 2 s
      before (control) and after (test) a 10 pulse, 100 Hz afferent train. In both WT
      and KO, the half-width (HW) of the test response, and its number of spikes, were
      augmented relative to the control. An increase in presynaptic release was not
      involved, because AMPAR-mediated EPSCs were depressed after a train. The
      increases in HW and spike number were both greater in the Car14 KO. In 0 Mg(2+)
      saline with picrotoxin (using a 20 Hz train), the HW measures were still greater
      in the KO. The Car inhibitor benzolamide (BZ) enhanced the test response HW in
      the WT but had no effect on the already-prolonged HW in the KO. With
      intracellular MK-801 [(+)-5-methyl-10,11-dihydro-5H-dibenzo [a,d]-cyclohepten
      5,10-imine maleate], the curtailed WT and KO responses were indistinguishable,
      and BZ caused no change. In contrast, the extracellular alkaline changes evoked
      by the train were not different between WT and KO, and BZ amplified these
      alkalinizations similarly. These data suggest that Car14 regulates pH transients
      in the perisynaptic microenvironment and govern their impact on NMDARs but plays
      little role in buffering pH shifts in the broader, macroscopic, extracellular
      space.

PMID- 23175831
TI  - No consistent bioenergetic defects in presynaptic nerve terminals isolated from
      mouse models of Alzheimer's disease.
AB  - Depressed cortical energy supply and impaired synaptic function are predominant
      associations of Alzheimer's disease (AD). To test the hypothesis that presynaptic
      bioenergetic deficits are associated with the progression of AD pathogenesis, we
      compared bioenergetic variables of cortical and hippocampal presynaptic nerve
      terminals (synaptosomes) from commonly used mouse models with AD-like phenotypes
      (J20 age 6 months, Tg2576 age 16 months, and APP/PS age 9 and 14 months) to age
      matched controls. No consistent bioenergetic deficiencies were detected in
      synaptosomes from the three models; only APP/PS cortical synaptosomes from 14
      month-old mice showed an increase in respiration associated with proton leak. J20
      mice were chosen for a highly stringent investigation of mitochondrial function
      and content. There were no significant differences in the quality of the
      synaptosomal preparations or the mitochondrial volume fraction. Furthermore,
      respiratory variables, calcium handling, and membrane potentials of synaptosomes
      from symptomatic J20 mice under calcium-imposed stress were not consistently
      impaired. The recovery of marker proteins during synaptosome preparation was the
      same, ruling out the possibility that the lack of functional bioenergetic defects
      in synaptosomes from J20 mice was due to the selective loss of damaged
      synaptosomes during sample preparation. Our results support the conclusion that
      the intrinsic bioenergetic capacities of presynaptic nerve terminals are
      maintained in these symptomatic AD mouse models.

PMID- 23175833
TI  - Not all errors are alike: theta and alpha EEG dynamics relate to differences in
      error-processing dynamics.
AB  - Performance errors in conflict tasks often result from inappropriate action
      impulses, and are thought to signal the need for increased control over the motor
      system. However, errors may also result from lapses in sustained attention, which
      may require different monitoring and adaptation mechanisms. Distinguishing
      between the mechanisms of adaptation is important as both error types may occur
      intermixed. To this end, we measured EEG of healthy human subjects while they
      performed three variants of the Simon task in which errors were more likely to
      occur due to attentional lapses, failures of motor control, or both. Behavioral
      results showed that subjects exhibited less conflict effects and less impulsive
      errors in sustained attention compared with the other Simon conditions. Time
      frequency analyses of EEG data showed that the sustained attention Simon
      condition, compared with the motor control Simon condition, was characterized by:
      (1) less error-related MFC theta (4-8 Hz) power and an absence of error-related
      MFC-DLPFC theta phase synchronization; (2) stronger error-related suppression of
      parieto-occipital alpha (8-12 Hz) power and stronger parieto-occipital-frontal
      alpha synchronization. A control experiment, using SART (the Sustained Attention
      to Response Test), confirmed that adaptation after attentional lapses involved
      posterior alpha power suppression, in addition to inter-regional frontal theta
      activity. Together, these results suggest that at least two cortical mechanisms
      exist for performance monitoring, and that different tasks and task-settings can
      recruit these mechanisms in a different way. Post-error brain dynamics thus
      consist of heterogeneous activity from multiple neurocognitive processes.

PMID- 23175832
TI  - Purging of memories from conscious awareness tracked in the human brain.
AB  - Understanding the neural basis of conscious experience and its regulation are
      fundamental goals of science. While recent research has made substantial progress
      in identifying the neural correlates of conscious experiences, it remains unclear
      how individuals exert control over the contents of awareness. In particular, can
      a memory that has entered the aware state be purged from consciousness if it is
      not currently desired? Here we tracked the correlates of consciousness in humans
      using functional magnetic resonance imaging and demonstrated the involvement of a
      downregulation mechanism that purges contents from conscious awareness. When
      individuals tried to prevent the retrieval of a memory in response to reminders,
      hippocampal activity was reduced, as previously established. Crucially, using
      trial-by-trial reports of phenomenal awareness, we found that this reduction of
      hippocampal activation was specifically associated with moments when a memory
      involuntarily intruded into conscious awareness and needed to be purged. This
      downregulation of activity during memory intrusions appears to disrupt momentary
      awareness of unwanted contents and, importantly, predicts impaired recall of the
      memory on later tests. These results tie the voluntary control of phenomenal
      awareness to observable changes in neural activity linked to awareness, and so
      provide a neurobiological model for guiding inquiry into the physical foundations
      of control over consciousness.

PMID- 23175834
TI  - A polymorphic microsatellite repeat within the ECE-1c promoter is involved in
      transcriptional start site determination, human evolution, and Alzheimer's
      disease.
AB  - Genetic factors strongly contribute to the pathogenesis of sporadic Alzheimer's
      disease (AD). Nevertheless, genome-wide association studies only yielded single
      nucleotide polymorphism loci of moderate importance. In contrast, microsatellite
      repeats are functionally less characterized structures within our genomes.
      Previous work has shown that endothelin-converting enzyme-1 (ECE-1) is able to
      reduce amyloid beta content. Here we demonstrate that a CpG-CA repeat within the
      human ECE-1c promoter is highly polymorphic, harbors transcriptional start sites,
      is able to recruit the transcription factors poly(ADP-ribose) polymerase-1 and
      splicing factor proline and glutamine-rich, and is functional regarding haplotype
      specific promoter activity. Furthermore, genotyping of 403 AD patients and 444
      controls for CpG-CA repeat length indicated shifted allelic frequency
      distributions. Sequencing of 245 haplotype clones demonstrated that the overall
      CpG-CA repeat composition of AD patients and controls is distinct. Finally, we
      show that human and chimpanzee [CpG](m)-[CA](n) ECE-1c promoter repeats are
      genetically and functionally distinct. Our data indicate that a short genomic
      repeat structure constitutes a novel core promoter element, coincides with human
      evolution, and contributes to the pathogenesis of AD.

PMID- 23175835
TI  - Postembryonic developmental changes in photoreceptors of the stick insect
      Carausius morosus enhance the shift to an adult nocturnal life-style.
AB  - Optimization of sensory processing during development can be studied by using
      photoreceptors of hemimetabolous insects (with incomplete metamorphosis) as a
      research model. We have addressed this topic in the stick insect Carausius
      morosus, where retinal growth after hatching is accompanied by a diurnal-to
      nocturnal shift in behavior, by recording from photoreceptors of first instar
      nymphs and adult animals using the patch-clamp method. In the nymphs, ommatidia
      were smaller and photoreceptors were on average 15-fold less sensitive to light
      than in adults. The magnitude of A-type K(+) current did not increase but the
      delayed rectifier doubled in adults compared with nymphs, the K(+) current
      densities being greater in the nymphs. By contrast, the density of light-induced
      current did not increase, although its magnitude increased 8.6-fold, probably due
      to the growth of microvilli. Nymph photoreceptors performed poorly, demonstrating
      a peak information rate (IR) of 2.9 +/- 0.7 bits/s versus 34.1 +/- 5.0 bits/s in
      adults in response to white-noise stimulation. Strong correlations were found
      between photoreceptor capacitance (a proxy for cell size) and IR, and between
      light sensitivity and IR, with larger and more sensitive photoreceptors
      performing better. In adults, IR peaked at light intensities matching irradiation
      from the evening sky. Our results indicate that biophysical properties of
      photoreceptors at each age stage and visual behavior are interdependent and that
      developmental improvement in photoreceptor performance may facilitate the switch
      from the diurnal to the safer nocturnal lifestyle. This also has implications for
      how photoreceptors achieve optimal performance.

PMID- 23175836
TI  - Positively biased processing of self-relevant social feedback.
AB  - Receiving social feedback such as praise or blame for one's character traits is a
      key component of everyday human interactions. It has been proposed that humans
      are positively biased when integrating social feedback into their self-concept.
      However, a mechanistic description of how humans process self-relevant feedback
      is lacking. Here, participants received feedback from peers after a real-life
      interaction. Participants processed feedback in a positively biased way, i.e.,
      they changed their self-evaluations more toward desirable than toward undesirable
      feedback. Using functional magnetic resonance imaging we investigated two
      feedback components. First, the reward-related component correlated with activity
      in ventral striatum and in anterior cingulate cortex/medial prefrontal cortex
      (ACC/MPFC). Second, the comparison-related component correlated with activity in
      the mentalizing network, including the MPFC, the temporoparietal junction, the
      superior temporal sulcus, the temporal pole, and the inferior frontal gyrus. This
      comparison-related activity within the mentalizing system has a parsimonious
      interpretation, i.e., activity correlated with the differences between
      participants' own evaluation and feedback. Importantly, activity within the MPFC
      that integrated reward-related and comparison-related components predicted the
      self-related positive updating bias across participants offering a mechanistic
      account of positively biased feedback processing. Thus, theories on both reward
      and mentalizing are important for a better understanding of how social
      information is integrated into the human self-concept.

PMID- 23175837
TI  - Long-term neural correlates of reversible fear learning in the lateral amygdala.
AB  - Fear conditioning and extinction are behavioral models that reflect the
      association and dissociation of environmental cues to aversive outcomes, both
      known to involve the lateral amygdala (LA). Accordingly, responses of LA neurons
      to conditioned stimuli (CS) increase after fear conditioning and decrease
      partially during extinction. However, the long-term effects of repeated fear
      conditioning and extinction on LA neuronal firing have not been explored. Here we
      show, using stable, high signal-to-noise ratio single-unit recordings, that the
      ensemble activity of all recorded LA neurons correlates tightly with conditioned
      fear responses of rats in a conditioning/extinction/reconditioning paradigm
      spanning 3 d. This CS-evoked ensemble activity increased after conditioning,
      decreased after extinction, and was repotentiated after reconditioning. Cell-by
      cell analysis revealed that among the LA neurons that displayed potentiated
      responses after initial fear conditioning, some exhibited weakened CS responses
      after extinction (extinction-susceptible), whereas others remained potentiated
      (extinction-resistant). The majority of extinction-susceptible neurons exhibited
      strong potentiation after reconditioning, suggesting that this distinct
      subpopulation (reversible fear neurons) encodes updated CS-unconditioned stimulus
      (US) association strength. Interestingly, these reversible fear neurons displayed
      larger, more rapid potentiation during reconditioning compared with the initial
      conditioning, providing a neural correlate of savings after extinction. In
      contrast, the extinction-resistant fear neurons did not show further increases
      after reconditioning, suggesting that this subpopulation encodes persistent fear
      memory representing the original CS-US association. This longitudinal report on
      LA neuronal activity during reversible fear learning suggests the existence of
      distinct populations encoding various facets of fear memory and provides insight
      into the neuronal mechanisms of fear memory modulation.

PMID- 23175838
TI  - The complex PrP(c)-Fyn couples human oligomeric Abeta with pathological tau
      changes in Alzheimer's disease.
AB  - Amid controversy, the cellular form of the prion protein PrP(c) has been proposed
      to mediate oligomeric amyloid-beta (Abeta)-induced deficits. In contrast, there
      is consistent evidence that the Src kinase Fyn is activated by Abeta oligomers
      and leads to synaptic and cognitive impairment in transgenic animals. However,
      the molecular mechanism by which soluble Abeta activates Fyn remains unknown.
      Combining the use of human and transgenic mouse brain tissue as well as primary
      cortical neurons, we demonstrate that soluble Abeta binds to PrP(c) at neuronal
      dendritic spines in vivo and in vitro where it forms a complex with Fyn,
      resulting in the activation of the kinase. Using the antibody 6D11 to prevent
      oligomeric Abeta from binding to PrP(c), we abolished Fyn activation and Fyn
      dependent tau hyperphosphorylation induced by endogenous oligomeric Abeta in
      vitro. Finally, we showed that gene dosage of Prnp regulates Abeta-induced
      Fyn/tau alterations. Together, our findings identify a complete signaling cascade
      linking one specific endogenous Abeta oligomer, Fyn alteration, and tau
      hyperphosphorylation in cellular and animal models modeling aspects of the
      molecular pathogenesis of Alzheimer's disease.

PMID- 23175840
TI  - Dynamic fluctuations in dopamine efflux in the prefrontal cortex and nucleus
      accumbens during risk-based decision making.
AB  - Mesocorticolimbic dopamine (DA) has been implicated in cost/benefit decision
      making about risks and rewards. The prefrontal cortex (PFC) and nucleus accumbens
      (NAc) are two DA terminal regions that contribute to decision making in distinct
      manners. However, how fluctuations of tonic DA levels may relate to different
      aspects of decision making remains to be determined. The present study measured
      DA efflux in the PFC and NAc with microdialysis in well trained rats performing a
      probabilistic discounting task. Selection of a small/certain option always
      delivered one pellet, whereas another, large/risky option yielded four pellets,
      with probabilities that decreased (100-12.5%) or increased (12.5-100%) across
      four blocks of trials. Yoked-reward groups were also included to control for
      reward delivery. PFC DA efflux during decision making decreased or increased over
      a session, corresponding to changes in large/risky reward probabilities. Similar
      profiles were observed from yoked-rewarded rats, suggesting that fluctuations in
      PFC DA reflect changes in the relative rate of reward received. NAc DA efflux
      also showed decreasing/increasing trends over the session during both tasks.
      However, DA efflux was higher during decision making on free- versus forced
      choice trials and during periods of greater reward uncertainty. Moreover, changes
      in NAc DA closely tracked shifts in choice biases. These data reveal dynamic and
      dissociable fluctuations in PFC and NAc DA transmission associated with different
      aspects of risk-based decision making. PFC DA may signal changes in reward
      availability that facilitates modification of choice biases, whereas NAc DA
      encodes integrated signals about reward rates, uncertainty, and choice,
      reflecting implementation of decision policies.

PMID- 23175839
TI  - A competition-based mechanism mediates developmental refinement of tectal neuron
      receptive fields.
AB  - Neural activity plays an important role in development and maturation of visual
      circuits in the brain. Activity can be instructive in refining visual projections
      by directly mediating formation and elimination of specific synaptic contacts
      through competition-based mechanisms. Alternatively, activity could be permissive
      regulating production of factors that create a favorable environment for circuit
      refinement. Here we used the Xenopus laevis tadpole visual system to test whether
      activity is instructive or permissive for shaping development of the retinotectal
      circuit. In vivo spike output was dampened in a small subgroup of tectal neurons,
      starting from developmental stages 44-46, by overexpressing Shaker-like Xenopus
      Kv1.1 potassium channels using electroporation. Tadpoles were then reared until
      stage 49, a time period when significant refinement of the retinotectal map
      occurs. Kv1.1-expressing neurons had significantly decreased spike output in
      response to both current injection and visual stimuli compared to untransfected
      controls, with spiking occurring during a more limited time interval. We found
      that Kv1.1-expressing neurons had larger visual receptive fields, decreased
      receptive field sharpness, and more persistent recurrent excitation than control
      neurons, all of which are characteristics of immature neurons. Transfected cells,
      however, had normal spontaneous excitatory synaptic currents and dendritic
      arbors. These results suggest that spike output of a tectal neuron plays an
      important instructive role in development of its receptive field properties and
      refinement of local circuits. However, other activity-dependent processes, such
      as synaptogenesis and dendritic growth, remain unaffected due to the permissive
      environment created by otherwise normal network activity.

PMID- 23175841
TI  - Plexin-B2 regulates the proliferation and migration of neuroblasts in the
      postnatal and adult subventricular zone.
AB  - In the postnatal forebrain, the subventricular zone (SVZ) contains a pool of
      undifferentiated cells, which proliferate and migrate along the rostral migratory
      stream (RMS) to the olfactory bulb and differentiate into granule cells and
      periglomerular cells. Plexin-B2 is a semaphorin receptor previously known to act
      on neuronal proliferation in the embryonic brain and neuronal migration in the
      cerebellum. We show here that, in the postnatal and adult CNS, Plexin-B2 is
      expressed in the subventricular zone lining the telencephalic ventricles and in
      the rostral migratory stream. We analyzed Plxnb2(-/-) mice and found that there
      is a marked reduction in the proliferation of SVZ cells in the mutant. Plexin-B2
      expression is downregulated in the olfactory bulb as interneurons initiate radial
      migration. BrdU labeling and GFP electroporation into postnatal SVZ, in addition
      to time-lapse videomicroscopy, revealed that neuroblasts deficient for Plexin-B2
      migrate faster than control ones and leave the RMS more rapidly. Overall, these
      results show that Plexin-B2 plays a role in postnatal neurogenesis and in the
      migration of SVZ-derived neuroblasts.

PMID- 23175842
TI  - Role of alpha-synuclein in adult neurogenesis and neuronal maturation in the
      dentate gyrus.
AB  - alpha-Synuclein has been reported to be important in modulating brain plasticity
      and to be a key protein in neurodegenerative diseases, including Lewy body
      dementia (LBD). We investigated how alpha-synuclein levels modulate adult
      neurogenesis and the development of dendritic arborization and spines in the
      dentate gyrus, in which new neurons are constantly added. In the human
      hippocampus, levels of endogenous alpha-synuclein were increased in LBD, and the
      numbers of SOX2-positive cells were decreased. We investigated whether newly
      generated neurons were modulated by endogenous alpha-synuclein, and we found
      increased adult neurogenesis in alpha/beta-synuclein knock-out mice. In contrast,
      overexpression of human wild-type alpha-synuclein (WTS) decreased the survival
      and dendritic development of newborn neurons. Endogenous alpha-synuclein
      expression levels increased the negative impact of WTS on dendrite development,
      suggesting a toxic effect of increasing amounts of alpha-synuclein. To attempt a
      rescue of the dendritic phenotype, we administered rolipram to activate the cAMP
      response element-binding protein pathway, which led to a partial rescue of
      neurite development. The current work provides novel insights into the role of
      alpha-synuclein in adult hippocampal neurogenesis.

PMID- 23175843
TI  - Robust representation of stable object values in the oculomotor Basal Ganglia.
AB  - Our gaze tends to be directed to objects previously associated with rewards. Such
      object values change flexibly or remain stable. Here we present evidence that the
      monkey substantia nigra pars reticulata (SNr) in the basal ganglia represents
      stable, rather than flexible, object values. After across-day learning of object
      reward association, SNr neurons gradually showed a response bias to surprisingly
      many visual objects: inhibition to high-valued objects and excitation to low
      valued objects. Many of these neurons were shown to project to the ipsilateral
      superior colliculus. This neuronal bias remained intact even after >100 d without
      further learning. In parallel with the neuronal bias, the monkeys tended to look
      at high-valued objects. The neuronal and behavioral biases were present even if
      no value was associated during testing. These results suggest that SNr neurons
      bias the gaze toward objects that were consistently associated with high values
      in one's history.

PMID- 23175844
TI  - Rab8 modulates metabotropic glutamate receptor subtype 1 intracellular
      trafficking and signaling in a protein kinase C-dependent manner.
AB  - Metabotropic glutamate receptors (mGluRs) are G protein-coupled receptors (GPCRs)
      that are activated by glutamate, the primary excitatory neurotransmitter in the
      CNS. Alterations in glutamate receptor signaling are implicated in
      neuropathologies such as Alzheimer's disease, ischemia, and Huntington's disease
      among others. Group 1 mGluRs (mGluR1 and mGluR5) are primarily coupled to
      Galpha(q/11) leading to the activation of phospholipase C and the formation of
      diacylglycerol and inositol 1,4,5-trisphosphate, which results in the release of
      intracellular calcium stores and protein kinase C (PKC) activation.
      Desensitization, endocytosis, and recycling are major mechanisms of GPCR
      regulation, and the intracellular trafficking of GPCRs is linked to the Rab
      family of small G proteins. Rab8 is a small GTPase that is specifically involved
      in the regulation of secretory/recycling vesicles, modulation of the actin
      cytoskeleton, and cell polarity. Rab8 has been shown to regulate the synaptic
      delivery of AMPA receptors during long-term potentiation and during constitutive
      receptor recycling. We show here that Rab8 interacts with the C-terminal tail of
      mGluR1a in an agonist-dependent manner and plays a role in regulating of mGluR1a
      signaling and intracellular trafficking in human embryonic kidney 293 cells.
      Specifically, Rab8 expression attenuates mGluR1a-mediated inositol phosphate
      formation and calcium release from mouse neurons in a PKC-dependent manner, while
      increasing cell surface mGluR1a expression via decreased receptor endocytosis.
      These experiments provide us with an understanding of the role Rabs play in
      coordinated regulation of mGluR1a and how this impacts mGluR1a signaling.

PMID- 23175846
TI  - Bottom-up biases in feature-selective attention.
AB  - Previous studies of feature-selective attention have focused on situations in
      which attention is directed to one of two spatially superimposed stimuli of equal
      salience. While such overlapping stimuli should maximize stimulus interactions,
      it is still unknown how bottom-up biases favoring one or the other stimulus
      influence the efficiency of feature-selective attention. We examined the
      integration of bottom-up contrast and top-down feature-selection biases on
      stimulus processing. Two fully overlapping random dot kinematograms (RDKs) of
      light and dark dots were presented on a gray background of intermediate
      luminance. On each trial, human participants attended one RDK to detect brief
      coherent motion targets, while ignoring any events in the unattended RDK.
      Concurrently, through changes in background luminance, stimulus contrast could be
      set to five different levels: the stimuli could either be equal, or one of the
      two stimuli could have twice or four times the contrast of the other stimulus.
      This manipulation introduced a bottom-up bias toward the stimulus with the higher
      contrast while keeping the difference between the stimuli constant. Stimulus
      processing was measured by means of steady-state visual evoked potentials
      (SSVEPs). SSVEP amplitudes generally increased with higher contrast of the
      driving stimulus. At earlier levels of processing, attention increased the slope
      of this linear relation, i.e., attention multiplicatively enhanced SSVEP
      amplitudes. However, at later levels of processing, attention had an additive
      effect. These effects of attention can be attributed to the differential
      integration of gain enhancement and inhibitory stimulus competition at different
      levels of the visual processing hierarchy.

PMID- 23175845
TI  - KCNQ channels determine serotonergic modulation of ventral surface chemoreceptors
      and respiratory drive.
AB  - Chemosensitive neurons in the retrotrapezoid nucleus (RTN) regulate breathing in
      response to CO(2)/H(+) changes. Their activity is also sensitive to
      neuromodulatory inputs from multiple respiratory centers, and thus they serve as
      a key nexus of respiratory control. However, molecular mechanisms that control
      their activity and susceptibility to neuromodulation are unknown. Here, we show
      in vitro and in vivo that KCNQ channels are critical determinants of RTN neural
      activity. In particular, we find that pharmacological block of KCNQ channels
      (XE991, 10 MUm) increased basal activity and CO(2) responsiveness of RTN neurons
      in rat brain slices, whereas KCNQ channel activation (retigabine, 2-40 MUm)
      silenced these neurons. Interestingly, we also find that KCNQ and apamin
      sensitive SK channels act synergistically to regulate firing rate of RTN
      chemoreceptors; simultaneous blockade of both channels led to a increase in CO(2)
      responsiveness. Furthermore, we also show that KCNQ channels but not SK channels
      are downstream effectors of serotonin modulation of RTN activity in vitro. In
      contrast, inhibition of KCNQ channel did not prevent modulation of RTN activity
      by Substance P or thyrotropin-releasing hormone, previously identified
      neuromodulators of RTN chemoreception. Importantly, we also show that KCNQ
      channels are critical for RTN activity in vivo. Inhibition of KCNQ channels
      lowered the CO(2) threshold for phrenic nerve discharge in anesthetized rats and
      decreased the ventilatory response to serotonin in awake and anesthetized
      animals. Given that serotonergic dysfunction may contribute to respiratory
      failure, our findings suggest KCNQ channels as a new therapeutic avenue for
      respiratory complications associated with multiple neurological disorders.

PMID- 23175848
TI  - Neurofibromin mediates FAK signaling in confining synapse growth at Drosophila
      neuromuscular junctions.
AB  - Neurofibromatosis type I (NF1), caused by the mutation in the NF1 gene, is
      characterized by multiple pathological symptoms. Importantly, ~50% of NF1
      patients also suffer learning difficulty. Although downstream pathways are well
      studied, regulation of the NF1-encoded neurofibromin protein is less clear. Here,
      we focused on the pathophysiology of Drosophila NF1 mutants in synaptic growth at
      neuromuscular junctions. Our analysis suggests that the Drosophila neurofibromin
      protein NF1 is required to constrain synaptic growth and transmission. NF1
      functions downstream of the Drosophila focal adhesion kinase (FAK) Fak56 and
      physically interacts with Fak56. The N-terminal region of NF1 mediates the
      interaction with Fak56 and is required for the signaling activity and presynaptic
      localization of NF1. In presynapses, NF1 acts via the cAMP pathway, but
      independent of its GAP activity, to restrain synaptic growth. Thus, presynaptic
      FAK signaling may be disrupted, causing abnormal synaptic growth and transmission
      in the NF1 genetic disorder.

PMID- 23175847
TI  - KAYAK-alpha modulates circadian transcriptional feedback loops in Drosophila
      pacemaker neurons.
AB  - Circadian rhythms are generated by well-conserved interlocked transcriptional
      feedback loops in animals. In Drosophila, the dimeric transcription factor
      CLOCK/CYCLE (CLK/CYC) promotes period (per), timeless (tim), vrille (vri), and
      PAR-domain protein 1 (Pdp1) transcription. PER and TIM negatively feed back on
      CLK/CYC transcriptional activity, whereas VRI and PDP1 negatively and positively
      regulate Clk transcription, respectively. Here, we show that the alpha isoform of
      the Drosophila FOS homolog KAYAK (KAY) is required for normal circadian behavior.
      KAY-alpha downregulation in circadian pacemaker neurons increases period length
      by 1.5 h. This behavioral phenotype is correlated with decreased expression of
      several circadian proteins. The strongest effects are on CLK and the neuropeptide
      PIGMENT DISPERSING FACTOR, which are both under VRI and PDP1 control.
      Consistently, KAY-alpha can bind to VRI and inhibit its interaction with the Clk
      promoter. Interestingly, KAY-alpha can also repress CLK activity. Hence, in flies
      with low KAY-alpha levels, CLK derepression would partially compensate for
      increased VRI repression, thus attenuating the consequences of KAY-alpha
      downregulation on CLK targets. We propose that the double role of KAY-alpha in
      the two transcriptional loops controlling Drosophila circadian behavior brings
      precision and stability to their oscillations.

PMID- 23175849
TI  - Detecting representations of recent and remote autobiographical memories in vmPFC
      and hippocampus.
AB  - How autobiographical memories are represented in the human brain and whether this
      changes with time are questions central to memory neuroscience. Two regions in
      particular have been consistently implicated, the ventromedial prefrontal cortex
      (vmPFC) and the hippocampus, although their precise contributions are still
      contested. The key question in this debate, when reduced to its simplest form,
      concerns where information about specific autobiographical memories is located.
      Here, we availed ourselves of the opportunity afforded by multivoxel pattern
      analysis to provide an alternative to conventional neuropsychological and fMRI
      approaches, by detecting representations of individual autobiographical memories
      in patterns of fMRI activity. We examined whether information about specific
      recent (two weeks old) and remote (10 years old) autobiographical memories was
      represented in vmPFC and hippocampus, and other medial temporal and neocortical
      regions. vmPFC contained information about recent and remote autobiographical
      memories, although remote memories were more readily detected there, indicating
      that consolidation or a change of some kind had occurred. Information about both
      types of memory was also present in the hippocampus, suggesting it plays a role
      in the retrieval of vivid autobiographical memories regardless of remoteness.
      Interestingly, we also found that while recent and remote memories were both
      represented within anterior and posterior hippocampus, the latter nevertheless
      contained more information about remote memories. Thus, like vmPFC, the
      hippocampus too respected the distinction between recent and remote memories.
      Overall, these findings clarify and extend our view of vmPFC and hippocampus
      while also informing systems-level consolidation and providing clear targets for
      future studies.

PMID- 23175851
TI  - Task-relevant and accessory items in working memory have opposite effects on
      activity in extrastriate cortex.
AB  - During visual search, the working memory (WM) representation of the search target
      guides attention to matching items in the visual scene. However, we can hold
      multiple items in WM. Do all these items guide attention at the same time? Using
      a new functional magnetic resonance imaging visual search paradigm, we found that
      items in WM can attain two different states that influence activity in
      extrastriate visual cortex in opposite directions: whereas the target item in WM
      enhanced processing of matching visual input, other "accessory" items in memory
      suppressed activity. These results imply that the representation of task-relevant
      and (currently) task-irrelevant representations in WM differs, revealing new
      insights into the organization of human visual WM. The suppressive influence of
      irrelevant WM items may complement the attention-guiding influence of task
      relevant WM items, helping us to focus on task-relevant information without
      getting distracted by irrelevant memory content.

PMID- 23175850
TI  - Suppression of beta1-integrin in gonadotropin-releasing hormone cells disrupts
      migration and axonal extension resulting in severe reproductive alterations.
AB  - Reproduction in mammals is dependent on the function of hypothalamic neurons
      whose axons project to the hypothalamic median eminence (ME) where they release
      gonadotropin-releasing hormone (GnRH) into a specialized capillary network for
      delivery to the anterior pituitary. These neurons originate prenatally in the
      nasal placode and migrate into the forebrain along the olfactory-vomeronasal
      nerves. The complex developmental events leading to the correct establishment of
      the GnRH system are tightly regulated by the specific spatiotemporal expression
      patterns of guidance cues and extracellular matrix molecules, the functions of
      which, in part, are mediated by their binding to beta1-subunit-containing
      integrins. To determine the biological role of these cell-surface proteins in
      reproduction, Cre/LoxP technology was used to generate GnRH neuron-specific beta1
      integrin conditional KO (GnRH-Itgb1(-/-)) mice. Loss of beta1-integrin signaling
      impaired migration of GnRH neurons, their axonal extension to the ME, timing of
      pubertal onset, and fertility in these mice. These results identify beta1
      integrin as a gene involved in normal development of the GnRH system and
      demonstrate a fundamental role for this protein in acquisition of normal
      reproductive competence in female mice.

PMID- 23175852
TI  - Differential distribution of glycine receptor subtypes at the rat calyx of Held
      synapse.
AB  - The properties of glycine receptors (GlyRs) depend upon their subunit
      composition. While the prevalent adult forms of GlyRs are heteromers, previous
      reports suggested functional alpha homomeric receptors in mature nervous tissues.
      Here we show two functionally different GlyRs populations in the rat medial
      nucleus of trapezoid body (MNTB). Postsynaptic receptors formed alpha1/beta
      containing clusters on somatodendritic domains of MNTB principal neurons,
      colocalizing with glycinergic nerve endings to mediate fast, phasic IPSCs. In
      contrast, presynaptic receptors on glutamatergic calyx of Held terminals were
      composed of dispersed, homomeric alpha1 receptors. Interestingly, the parent cell
      bodies of the calyces of Held, the globular bushy cells of the cochlear nucleus,
      expressed somatodendritic receptors (alpha1/beta heteromers) and showed similar
      clustering and pharmacological profile as GlyRs on MNTB principal cells. These
      results suggest that specific targeting of GlyR beta-subunit produces segregation
      of GlyR subtypes involved in two different mechanisms of modulation of synaptic
      strength.

PMID- 23175853
TI  - Transmitter release from cochlear hair cells is phase locked to cyclic stimuli of
      different intensities and frequencies.
AB  - The auditory system processes time and intensity through separate brainstem
      pathways to derive spatial location as well as other salient features of sound.
      The independent coding of time and intensity begins in the cochlea, where
      afferent neurons can fire action potentials at constant phase throughout a wide
      range of stimulus intensities. We have investigated time and intensity coding by
      simultaneous presynaptic and postsynaptic recording at the hair cell-afferent
      synapse from rats. Trains of depolarizing steps to the hair cell were used to
      elicit postsynaptic currents that occurred at constant phase for a range of
      membrane potentials over which release probability varied significantly. To probe
      the underlying mechanisms, release was examined using single steps to various
      command voltages. As expected for vesicular release, first synaptic events
      occurred earlier as presynaptic calcium influx grew larger. However, synaptic
      depression produced smaller responses with longer first latencies. Thus, during
      repetitive hair cell stimulation, as the hair cell is more strongly depolarized,
      increased calcium channel gating hurries transmitter release, but the resulting
      vesicular depletion produces a compensatory slowing. Quantitative simulation of
      ribbon function shows that these two factors varied reciprocally with hair cell
      depolarization (stimulus intensity) to produce constant synaptic phase. Finally,
      we propose that the observed rapid vesicle replenishment would help maintain the
      vesicle pool, which in turn would equilibrate with the stimulus intensity (and
      therefore the number of open Ca(2+) channels), so that for trains of different
      levels the average phase will be conserved.

PMID- 23175855
TI  - Neurophysiological correlates of dissociative symptoms.
AB  - OBJECTIVE: Dissociation is a mental process with psychological and somatoform
      manifestations, which is closely related to hypnotic suggestibility and
      essentially shows the ability to obtain distance from reality. An increased
      tendency to dissociate is a frequently reported characteristic of patients with
      functional neurological symptoms and syndromes (FNSS), which account for a
      substantial part of all neurological admissions. This review aims to investigate
      what heart rate variability (HRV), EEG and neuroimaging data (MRI) reveal about
      the nature of dissociation and related conditions. METHODS: Studies reporting
      HRV, EEG and neuroimaging data related to hypnosis, dissociation and FNSS were
      identified by searching the electronic databases Pubmed and ScienceDirect.
      RESULTS: The majority of the identified studies concerned the physiological
      characteristics of hypnosis; relatively few investigations on dissociation
      related FNSS were identified. General findings were increased parasympathetic
      functioning during hypnosis (as measured by HRV), and lower HRV in patients with
      FNSS. The large variety of EEG and functional MRI investigations with diverse
      results challenges definite conclusions, but evidence suggests that subcortical
      as well as (pre)frontal regions serve emotion regulation in dissociative
      conditions. Functional connectivity analyses suggest the presence of altered
      brain networks in patients with FNSS, in which limbic areas have an increased
      influence on motor preparatory regions. CONCLUSIONS: HRV, EEG and (functional)
      MRI are sensitive methods to detect physiological changes related to dissociation
      and dissociative disorders such as FNSS, and can possibly provide more
      information about their aetiology. The use of such measures could eventually
      provide biomarkers for earlier identification of patients at risk and appropriate
      treatment of dissociative conditions.

PMID- 23175854
TI  - Paediatric autoimmune encephalopathies: clinical features, laboratory
      investigations and outcomes in patients with or without antibodies to known
      central nervous system autoantigens.
AB  - OBJECTIVE: To report the clinical and investigative features of children with a
      clinical diagnosis of probable autoimmune encephalopathy, both with and without
      antibodies to central nervous system antigens. METHOD: Patients with
      encephalopathy plus one or more of neuropsychiatric symptoms, seizures, movement
      disorder or cognitive dysfunction, were identified from 111 paediatric serum
      samples referred from five tertiary paediatric neurology centres to Oxford for
      antibody testing in 2007-2010. A blinded clinical review panel identified 48
      patients with a diagnosis of probable autoimmune encephalitis whose features are
      described. All samples were tested/retested for antibodies to N-methyl-D
      aspartate receptor (NMDAR), VGKC-complex, LGI1, CASPR2 and contactin-2, GlyR,
      D1R, D2R, AMPAR, GABA(B)R and glutamic acid decarboxylase. RESULTS: Seizures
      (83%), behavioural change (63%), confusion (50%), movement disorder (38%) and
      hallucinations (25%) were common. 52% required intensive care support for seizure
      control or profound encephalopathy. An acute infective organism (15%) or abnormal
      cerebrospinal fluid (32%), EEG (70%) or MRI (37%) abnormalities were found. One
      14-year-old girl had an ovarian teratoma. Serum antibodies were detected in 21/48
      (44%) patients: NMDAR 13/48 (27%), VGKC-complex 7/48(15%) and GlyR 1/48(2%).
      Antibody negative patients shared similar clinical features to those who had
      specific antibodies detected. 18/34 patients (52%) who received immunotherapy
      made a complete recovery compared to 4/14 (28%) who were not treated; reductions
      in modified Rankin Scale for children scores were more common following
      immunotherapies. Antibody status did not appear to influence the treatment
      effect. CONCLUSIONS: Our study outlines the common clinical and paraclinical
      features of children and adolescents with probable autoimmune encephalopathies.
      These patients, irrespective of positivity for the known antibody targets,
      appeared to benefit from immunotherapies and further antibody targets may be
      defined in the future.

PMID- 23175857
TI  - What are we? What should we be?

PMID- 23175856
TI  - Overlooked non-motor symptoms in myasthenia gravis.
AB  - Patients with myasthenia gravis (MG) may have various non-motor symptoms in
      addition to fatigability and weakness of skeletal muscles. Thymomas contain
      abundant immature thymocytes and developing CD4 and CD8 T cells. Thymomas are
      found in 15-25% of patients with MG and are associated with severe symptoms. We
      suggest that non-motor symptoms are based on the autoimmune disorders probably
      owing to an abnormal T cell repertoire from thymomas. Using previously reported
      cases and cases from our multicentre cooperative study, we review the clinical
      characteristics of patients with thymoma-associated MG who have non-motor
      symptoms. CD8 T cell cytotoxicity against haematopoietic precursor cells in bone
      marrow and unidentified autoantigens in hair follicles lead to the development of
      pure red cell aplasia, immunodeficiency and alopecia areata. In contrast,
      neuromyotonia, limbic encephalitis, myocarditis and taste disorders are
      autoantibody-mediated disorders, as is MG. Autoantibodies to several types of
      voltage-gated potassium channels and the related molecules can evoke various
      neurological and cardiac disorders. About 25% of patients with thymoma-associated
      MG have at least one non-motor symptom. Non-motor symptoms affect many target
      organs and result in a broad spectrum of disease, ranging from the impairment of
      quality of life to lethal conditions. Since relatively little attention is paid
      to non-motor symptoms in patients with thymoma-associated MG, the symptoms may be
      overlooked by many physicians. Early diagnosis is important, since non-motor
      symptoms can be treatable. A complete understanding of non-motor symptoms is
      necessary for the management of patients with thymoma-associated MG. 

PMID- 23175858
TI  - Assessing evidence in public health: the added value of GRADE.

PMID- 23175859
TI  - NICE public health update.

PMID- 23175860
TI  - Should you skip your PSA test? The science is uncertain for now, so arm yourself
      with deep knowledge of the pros and cons of prostate cancer screening.

PMID- 23175861
TI  - On call.  I am 72 years old and in good health, but I am lactose intolerant and
      can't drink milk to obtain calcium.  Should I take calcium supplements?

PMID- 23175862
TI  - On call. My skin is always very dry and itchy. What is the best treatment? Could
      it be something other then just dry skin?

PMID- 23175863
TI  - Is low-dose aspirin safe for you?  If you take daily aspirin, make sure you know
      why and understand the small but real bleeding risk.

PMID- 23175864
TI  - Testing your testosterone: it's tricky. Diagnosing and confirming low
      testosterone requires thorough lab testing and careful interpretation of the
      results.

PMID- 23175865
TI  - Stomach-soothing steps for heartburn. First, change the behaviors that contribute
      to heartburn. If the pain persists, medications called PPIs are highly effective.

PMID- 23175866
TI  - Not requiring a co-pay boosts colorectal screening.

PMID- 23175867
TI  - Large waistline linked to urinary and erectile difficulties.

PMID- 23175868
TI  - "Keyhole" vein removal for bypass is safe.

PMID- 23175869
TI  - Popular cardiac drug may prevent pneumonia.

PMID- 23175870
TI  - High sensitive C-reactive protein for prediction of adverse outcome in acute
      exacerbation of chronic obstructive pulmonary disease.
AB  - Hospitalization for acute exacerbation of chronic obstructive pulmonary disease
      (AECOPD) is associated with a high risk of mortality and complications. The goal
      of the study is to assess the clinical utility of serum high sensitive C-reactive
      protein (hs-CRP) at admission in predicting outcome in hospitalized patients with
      AECOPD. METHODS: Consecutive patients with AECOPD admitted to a public teaching
      hospital were studied prospectively. The adverse outcome defined occurrence of
      one or more of: (1) death in hospital or within 30 days after discharge, (2)
      transfer to the intensive care unit, or (3) intubation and mechanical
      ventilation. The correlation of hs-CRP with duration of hospitalization and FEV1%
      of predicted is also calculated. RESULTS: Of 60 patients, 22 had adverse outcome
      and 38 good outcomes. There were no significant differences between two group for
      mean age, gender, smoking status, and previous hospitalizations (p > 0.05). The
      adverse outcome rate was 56.5% in those with serum hs-CRP equal or more than 100
      mg/ml versus 24.3% in patients with hs-CRP less 100 mg/ml (p = 0.01).
      CONCLUSIONS: Serum hs-CRP at admission is a predictor of outcome in AECOPD.
      Admission hs-CRP higher than 100 mg/ml was associated with near fourfold
      increased probability of adverse outcome.

PMID- 23175871
TI  - Distribution and characteristics of non carious cervical lesions in an adult
      Nigerian population.
AB  - BACKGROUND: Controversies rages in the literature as to the characteristics of
      non carious cervical lesions (NCCLs) in terms of the location and its severity.
      OBJECTIVE: The study is to investigate the characteristics of NCCLs in adult
      patients who had a high incidence in them and to see if there are any association
      with the findings. Methods : The author examined 356 teeth with NCCLs in 34
      subjects (male and female aged 22-75 years). The characteristics were based on
      the location of the lesion and the size (shape, extensiveness and depth).
      RESULTS: In terms of the location, 61.2% were located on the posterior teeth, and
      55.9% on the maxillary teeth. The first premolars (25.8%) and canines (19.4%)
      were affected most often, followed by the first molars (16.9%) and second
      premolars (13.8%). There was slight right side preponderance (50.3%) and more
      lesions in the male subjects (67.4%). Patients tended to be older, with 76.4% in
      the 40 years and older age group. In terms of the size of the lesion, 75.0% of
      the lesion had angular shape of < 135 (wedge), 70.2% had axial depth of 1-2 mm,
      and 51.7% had occlusogingival width (extensiveness) of 2-3.9mm (small). There was
      association between gender and the severity (extensiveness) of the lesion. The
      severity (shape and extensiveness) of NCCL was associated with age. There was
      strong association between the severity of NCCL and site of the lesion (jaws).
      CONCLUSION: The authors found that NCCLs were significantly related to age. The
      posterior maxillary teeth especially the first premolars followed by the canines
      were the teeth commonly involved. No great difference in incidence was found
      between the right and left sides as a result of right or left hand dexterity.
      Awareness of a multifactorial etiology in noncarious cervical lesions may help
      the clinician to formulate an appropriate treatment plan for the patient. In
      addition, these characteristics help identify which teeth and patients that are
      more susceptible.

PMID- 23175872
TI  - Pattern of periodontal treatments performed at the periodontology clinic of the
      Lagos University Teaching Hospital: 22 months review.
AB  - BACKGROUND: A critical evaluation of the pattern of periodontal procedures
      performed is important in providing useful data to the administrator for proper
      planning and budgeting for dental health service. OBJECTIVE: To assess the
      pattern of periodontal treatments performed over a given period of time at the
      Periodontology clinic of the Lagos University Teaching Hospital, Lagos, Nigeria.
      METHODS: This was a twenty two months retrospective study of all periodontal
      procedures performed on patients seen at the periodontology clinic of the Lagos
      University Teaching Hospital between January 2006 and October 2007. The
      periodontology treatment record was used to retrieve information which included
      the patient's age, gender, diagnosis and periodontal procedures given. The
      procedures were further categorized into surgical and nonsurgical groups. The
      information obtained was then analyzed using Epi Info 2007 statistical software.
      RESULTS: A total of 1,938 patients were seen during this period. Females were
      1009 (52.1%) and males were 929 (47.9%). (F/M, 1.1:1). A total of 2,110
      periodontal treatments were performed. Majority of the patients received non
      surgical periodontal therapy which constituted the bulk (96.3%) of the therapies.
      Scaling and polishing was the most frequently performed non-surgical procedure
      accounting for 1261 (62.1%) with slightly more males receiving the treatment. Of
      the surgical treatment modalities, operculectomy accounted for 65.4% and was
      carried out on more females than males. Regenerative procedures were the least
      performed surgical treatments. CONCLUSION: This study highlighted that non
      surgical periodontal therapy, particularly scaling and polishing was the most
      frequently utilized periodontal procedure. Operculectomy was the predominant
      surgical procedure performed. The low percentage of regenerative surgical
      procedures was however below the desired expectation.

PMID- 23175873
TI  - Clinical and proctosigmoidoscopic findings in patients with anorectal sepsis in a
      private health facility in Lagos, Nigeria.
AB  - BACKGROUND: Anorectal sepsis is a distressing condition which is sometimes
      inadequatelytreated. OBJECTIVES: To determine the clinical and
      prostosigmoidoscopic findings in patients with anorectal sepsis seen by the
      authors over a 5 year period as well as identifying the commonly performed
      procedures. METHOD: A review of all the records of patients seen by the authors
      over a 5 year period was carried out. The demographic pattern was determined
      including the age, sex, mode of presentation, and associated co-morbidities. The
      detailed perianal and protosigmoidoscopic findings were also noted RESULTS: 45
      males and 10 females were seen during the study period. The mean age incidence
      was 43.4 years. The commonest mode of presentation was perianal discharge and
      pain in over 85% of the patients seen. The low anal fistula was the commonest
      pathology on proctosigmoidoscopy while abscesses and external haemorrhoids were
      the other commonly occurring lesions found . Fistulotomy was the most commonly
      perfomed procedure while diabetes was the most common comorbidity. CONCLUSION:
      Anorectal sepsis most commonly affects males in the fifth decade of life.
      Thorough evaluation and adequate operative treatment appear to result in
      satisfactory early outcome.

PMID- 23175874
TI  - Knowledge of health insurance among primary health-care managers in Shongom LGA,
      Gombe State, Nigeria.
AB  - BACKGROUND: The National Health Insurance Scheme (NHIS) was formally launched in
      Nigeria in 2005 as an option to help bridge the evident gaps in health care
      financing, with the expectation of it leading to significant improvement in the
      country's dismal health status indices. Primary Health Care (PHC) is the nation's
      adopted strategy for health service delivery and its managers are central to the
      success of any health-related programme. There is paucity of specific data about
      what this critical group of people know about health insurance. OBJECTIVE: The
      objective of the study was to assess the level of knowledge of managers of the
      Shongom PHC system about health insurance. METHODS: The study was of a
      descriptive cross-sectional design carried out among twenty-eight PHC managers of
      government-provided and community-owned health facilities/units in Shongom LGA,
      Gombe State, northeastern Nigeria. RESULTS: Among the respondents, 17.9% had good
      knowledge about health insurance while 35.7% and 46.4% had fair and poor scores
      respectively. Respondents in government-provided facilities/units had 6.3%, 37.5%
      and 56.3% for good, fair and poor scores respectively, while their counterparts
      in community-owned facilities had 33.3% for each of the score grades. CONCLUSION:
      The research showed that knowledge about health insurance among managers in this
      rural PHC system was below average.

PMID- 23175875
TI  - Spinal neural tube defects in Lagos University Teaching Hospital, Nigeria.
AB  - BACKGROUND: The incidence of neural tube defects is known to vary among regions.
      Very little has been reported about the incidence in Sub-Saharan Africa except
      for the general impression that the prevalent rates are low. OBJECTIVE: To
      determine the profile of patients presenting with neural tube defects in Lagos,
      Nigeria METHODS: We studied all patients with congenital midline back swellings
      presenting to one of two neurosurgical services in the state over a 5-year period
      to establish the incidence of spina bifida and develop demographic data. Data
      collected included the age at presentation, maternal age, education and parity,
      presence of co-existing anomalies and the social status of the parents. RESULTS:
      One hundred and eight patients with congenital midline swellings of the back were
      studied. Meningomyelocele accounted for 96% of the cases seen. Half the patients
      presented within the first two weeks of life and although fifty percent of
      mothers had ultrasound scans done during pregnancy none of the patients were
      diagnosed prenatally. Seventy-three percent of mothers of affected children were
      from a low socio-economic class. The commonest co-existing congenital anomaly was
      lower limb deformity (Talipes equino-varus). CONCLUSION: Spina bifida is the
      commonest indication for neurosurgical clinic referral with the exception of
      trauma in our environment. The prevalence is higher among women in the lower
      socio-economic groups. Improved perinatal care is required to ensure that
      children with such birth defects get prompt medical attention and thereby prevent
      worsening of an already complex problem.

PMID- 23175876
TI  - Circulating adipokine levels in type 2 diabetes mellitus in Lagos, Nigeria.
AB  - BACKGROUND: Type 2 diabetes remains a global concern with its numerical increase
      occurring in developing countries which include Nigeria. Adipose tissue-secreted
      factors called "adipokines" are involved in energy homeostasis and regulation of
      glucose and lipid metabolism. OBJECTIVE: This study was undertaken with the aim
      of investigating adipokine levels in the Type 2 Diabetes Mellitus. METHODS: This
      is a cross sectional study conducted in Lagos University Teaching Hospital
      (LUTH), a-700 bed tertiary hospital centre in Lagos, Nigeria. 53 diabetic
      subjects and 27 non-diabetic controls with mean age (56.72 +/- 10.44) and (38.67
      +/- 9.63) years respectively, were recruited into the study. Fasting blood
      glucose, HbA1 C, leptin and resistin levels and body mass index (BMI) were
      assayed. RESULTS: Mean BMI was higher but not statistically significant in
      diabetics than in non diabetics (diabetics 28.77 +/- 5.35; non diabetics 27.38 +/
      6.04; p > 0.05). Resistin level was significantly higher in diabetics (31.26 +/-
      2.5) as compared with non diabetics (16.61 +/- 2.16) compared to non-diabetics.
      Leptin correlated very strongly with BMI (r = 0.620, p < 0.0001) and was
      significantly higher in females than males (female 9.72 +/- 1.70; male 1.79 +/-
      0.54; p < 0.0001). CONCLUSION: The circulating adipokines have variable effect on
      the glucose and fat metabolism. BMI and resistin level were higher in diabetics.
      Leptin was found in this study to correlate very strongly with BMI (adiposity).
      There was also a strong gender dependence observed as leptin level was
      signficantly higher in females than males.

PMID- 23175877
TI  - The antidiarrhoeal activity of the aqueous root extract of Aristolochia ringens
      (Vahl.) Aristolochiaceae.
AB  - BACKGROUND: Aristolochia ringens, an ornamental plant native to tropical America
      that now grows in a number of African countries has been reported to be used in
      African traditional medicine for the management of snake bite venom,
      gastrointestinal disturbances, rheumatoicd arthritis and insomnia among others.
      OBJECTIVE: Based on its use in traditional African medicine, the antidiarrhoeal
      activity of the aqueous root extract of Aristolochia ringens (AR) was evaluated
      to determine the pharmacological basis of its use in the management of diarrhoea.
      METHODS: Normal and castor oil (CO) induced intestinal transit, castor oil
      induced diarrhoea, gastric emptying and enteropooling models were carried out in
      mice and rats. Preliminary phytochemical screening and acute toxicity tests were
      also carried out. RESULTS: AR (100-400 mg/kg, p.o.) produced a dose-dependent and
      significant decrease in normal and castor oil-induced intestinal transit compared
      to the vehicle group. This effect was significantly (p < 0.001) inhibited by
      pilocarpine (10 mg/kg, s.c.), phentolamine and propranolol (1 mg/kg, i.p.)
      respectively but neither significantly inhibited by yohimbine (1 mg/kg, s.c.) nor
      significantly enhanced by isosorbide dinitrate (150 mg/kg, p.o.). AR produced a
      dose-dependent and significant increase in the latency of diarrhoeal onset. AR
      also reduced the diarrhoeal score, number and weight of wet stools. The in vivo
      antidarrhoeal index (ADI(in vivo)) of 81.79 produced by AR (400 mg/kg) is
      comparable to the 86.85 ADI(in vivo). produced by morphine (10 mg/kg, s.c.). AR
      also reduced the gastric enteropooling and emptying effects of castor oil.
      Preliminary screening showed the presence of tannins, saponins and alkaloids. In
      the acute toxicity study, no mortality was observed with AR administered orally
      up to 10,000 mg/kg, but an LD50 of 407.38 mg/kg was obtained with the
      intraperitoneal route of administration in mice. CONCLUSION: Results show that
      the aqueous root extract of Aristolochia ringens possesses antidiarrhoeal
      activity possibly mediated by its non selective action on adrenoceptors in the
      GIT and physiological antagonism of the parasympathetic nervous system.

PMID- 23175878
TI  - The relationship between microalbuminuria, cardiovascular risk factors and
      disease management in type 2 diabetes.
AB  - BACKGROUND: In patients with type 2 diabetes, microalbuminuria is an early
      clinical sign suggestive of vascular damage to the glomerulus. Microalbuminuria
      has also been currently reported as an important risk factor for cardiovascular
      disease and becomes relevant in the management of type 2 diabetes. OBJECTIVES:
      This study is to determine the prevalence of microalbuminuria, identify the risk
      factors associated with microalbuminuria in type 2 diabetes, and to asses the
      achievement of treatment goals for cardiovascular risk reduction in type 2
      diabetics. SUBJECTS AND METHODS: Seventy- two subjects with microalbuminuria were
      recruited from three hundred consecutively screened type 2 diabetics attending
      the Diabetic Clinic at the Lagos University Teaching Hospital. Clinical data were
      obtained by interviewing the participants. Anthropometric measurements were made
      and blood specimens were collected for analysis. RESULTS: The prevalence of
      microalbuminuria was twenty-four percent (24%) in type 2 diabetes. Multiple
      logistic regression identified duration of diabetes (odds ratio 1.3 (95% CI; 0.03
      1.58), hypertension(odds ratio 5.2 (95% Cl; 1.24-18.62), Body mass index (BMI)
      (odds ratio 1.27 (95% CI; 1.0-1.6), waist/hip ratio (WHR) (odds ratio 1.9 (95%
      Cl; 1.3-3.5), andHbA,c (odds ratio 6.6 (95% Cl; 1.02-27) as independent risk
      factors associated with microalbuminuria in type 2 diabetics. Optimum blood
      pressure, glycemic and weight control were achieved in eighty five percent (85%),
      fifty eight percent (58%) and nineteen percent (19%) of the type 2 diabetes
      respectively. CONCLUSION: This study showed that microalbuminuria is common among
      patients with type 2 diabetes. It also showed improvement in glycemic control and
      modifiable cardiovascular risk factor control when compared with previous
      studies.

PMID- 23175879
TI  - Pattern of conjunctival masses seen at Guinness Eye Centre Luth Idi-Araba.
AB  - BACKGROUND: Conjunctival masses are growth on the surface of the outer eye; which
      may represent benign or malignant transformations. OBJECTIVE: To determine the
      pattern of presentation of conjunctival masses at the Guinness Eye Centre (GEC),
      Lagos University Teaching Hospital (LUTH) Idi-Araba over a 13 year period (Jan
      1995-Dec 2007). METHOD: A retrospective review of the clinical notes of all
      patients that presented to GEC with conjunctival masses during the study period
      was carried out. The bio-data, clinical features, stage, laterality and
      associated features of the masses were noted. The diagnosis, treatment and
      complications of treatment were also recorded. RESULTS: Case notes of 612 eyes of
      393 patients were included in the study. There were 219 (55.7%) males, 174
      (44.3%) females with ages ranging from 4-85 years with a male to female ratio of
      1.26: 1. Three hundred and eighty-eight patients (98.7%) presented as elective
      cases to the outpatient department while 5 (1.3%) presented as emergencies on
      account of associated ocular inflammation. There were 220 (56%) bilateral masses
      while 44% were uniocular. Pterygium was the leading conjunctival mass affecting
      548 eyes (89.5%) of 329 patients. Pingueculae occurred in 53 eyes (8.7%),
      conjunctival cysts in 5 (0.8%) eyes, neoplastic growths in 3 (0.5%) eyes,
      conjunctival granulomas in 2 (0.3%) eyes and limbal teratoma in 1 (0.2%) eye.
      Most of these patients defaulted from surgery as only 141 eyes (23%) of 121
      patients had surgery. Post-operative complications occurred in 33 eyes (5.4%) of
      30 patients. The commonest postoperative complication was pterygium recurrence
      which occurred in 18 eyes of 15 patients. CONCLUSION: Pterygium was the commonest
      conjunctival mass and preventive strategies need to be advocated. Prevention of
      recurrence remains a challenge in the management of pterygium as recurrence after
      surgical excision occurred in 13.2% of eyes. Our study however did not confirm
      outdoor occupations as a risk factor for pterygium.

PMID- 23175880
TI  - A classification system for recurrent ameloblastoma of the jaws--review of 30
      cases in Nigerians.
AB  - This paper reviewed the clinicopathologic presentation of recurrent ameloblastoma
      in 30 Nigerian patients at three tertiary referral centers with the sole
      objective of developing a classification system. Most recurrences occurred in
      patients in their 3rd decade of life (20-29years) and males were more frequently
      affected than females (1.5 to 1). Though enucleation resulted in the highest rate
      of recurrences (30%), hemi-mandibulectomy also resulted in a 20% recurrence rate.
      Majority of the recurrences occurred within 5 to 9 years after primary surgery.
      Most primary jaw sites of the lesion corresponded with the primary jaw sites of
      the recurrent tumor which in itself may be a reflection of inadequate primary
      treatment. The most frequent anatomic site of primary tumors that recurred was c4
      (highest level of ramus involvement). The most frequent anatomic classification
      of the recurrent tumors was recurrence at one bone margin (Bla) and recurrence at
      intervening /adjacent soft tissues between the resected bone edges (Blc).
      Mandible to maxilla recurrence increases the likelihood of extension to the skull
      and brain.

PMID- 23175881
TI  - Ocular findings in acquired immunodeficiency syndrome patients in Lagos, Nigeria.
AB  - BACKGROUND: There is paucity of studies on the prevalence and pattern of ocular
      complication in HIV patients in developing countries where 90% of all HIV
      sufferers live. Most studies were carried out in industrialized countries and are
      not representative of the spectrum of ocular complication of HIV and it's
      prevalence in developing countries. OBJECTIVE: To determine the prevalence of
      ocular disorders in adult (> 15 years ) AIDS patients at PEPFAR clinic in Lagos,
      Nigeria. MATERIAL AND METHODS: All consecutive adult Seropositive HIV/AIDS
      patients of PEPFAR Clinic at the Lagos University Teaching Hospital between
      February 1st-March 15th 2008 were enrolled into the study Cross sectional and non
      randomized, convenient study was used. Biodata and medical history were recorded
      on interviewer administered questionnaire. Participants were examined according
      to standard protocol comprising visual acuity, intraocular pressure, anterior
      segment examination with slit lamp biomicroscopy, dilated fundoscopy and fundus
      photograph where necessary. PCV, CD4+ count, viral load at diagnosis, stage of
      HIV disease were extracted from patients' records. Details of drug were regimen
      also recorded. Data analysis was performed with EPI-lnfo 6.04 version; Chi square
      and student t test used to describe statistical association. RESULTS: A total of
      400 patients were studied. Male:female ratio was 1.7 and mean age was 40 years
      (S.D. + 9.12). Ocular disorders seen in 78.5% of patients; HIV related ocular
      disorders occurred in 45 (11.3) patients. Conjunctival microvasculopathy 166
      patients (41.5%), pingueculum in 114 (28.5%), pterygium in 76 (19.0%), refractive
      error in 93 (23.3%), cataract in 12 (3.0%), and 22 (5.5%) Glaucoma suspects. HIV
      retinopathy and allergic eye disease in one patient each (0.3%). Presumed
      Cytomegalovirus retinitis 7 (1.8%), 14 (3.5%) Toxoplasmosis, 8 (2.0%) HZO, and 15
      (3.8%) Presumed Squamous cell carcinoma. Eighty six (21.5%) of the patients had
      no abnormality. 91.4% of eyes examined had visual acuity with best correction of
      > 6/18. CD4+ in 79.3% of the patients was > 200 cells/ul and < 5% had counts < 50
      cells with an overall mean of 406 cell/ul. 375 (93.8%) patients were on Highly
      Active Antiretroviral therapy (HAART), and 25 (6.2%) were not. CONCLUSION: Study
      revealed low prevalence of HIV related ocular disorders. This could be due to few
      patients at low level of immunosuppresion where the infections occur.

PMID- 23175882
TI  - Spectrum of endoscopic findings in Nigerians with dyspepsia.
AB  - BACKGROUND: Dyspepsia is a common gastrointestinal disorder originating from the
      gastroduodenal region, and is the most common indication for upper
      gastrointestinal tract endoscopy. There are differing information on the
      commonest endoscopic findings in patients with dyspepsia from Nigeria. OBJECTIVE:
      The aim of this study was to determine the spectrum of endoscopic findings in
      patients with dyspepsia. PATIENTS AND METHODS: This is a hospital-based
      prospective study carried out at the Endoscopy Unit of Federal Medical Centre,
      Yola from November, 2006 to May, 2010. Patients with clinical features of
      dyspepsia who underwent upper gastrointestinal tract endoscopy as part of their
      workup were recruited. Their biodata, history and duration of dyspepsia were
      noted on a proforma. The spectrum of endoscopic findings was also noted. RESULTS:
      A total of 259 patients with dyspepsia had upper gastrointestinal tract
      endoscopy. Ninety-nine (38.2%) were males while 160 (61.8%) were females, giving
      a male to female ratio of 1:1.6. Clinically significant endoscopic findings were
      seen in 241 (93.1%) patients while gastroduodenitis was the commonest finding.
      One hundred and two (39.4%) patients had two endoscopic findings, and 7 (2.7%)
      had three findings. CONCLUSION: Majority of patients with dyspepsia had
      clinically significant endoscopic findings. Gastroduodenitis was the commonest
      endoscopic finding.

PMID- 23175883
TI  - Diverticulosis of the colon: a report of two cases.
AB  - BACKGROUND: Diverticula are bulging pouch-like herniations in the wall of the
      hollow organ anywhere in the gastrointestinal tract from the oesophagus to the
      colon. Diverticula are thought to occur more commonly in the colon than in any
      other segment of the gastrointestinal tract. It may be asymptomatic or
      complicated by diverticulitis (diverticular inflammation), bleeding, or
      perforation with peritonitis. It could be potentially life threatening. It was
      thought to be rare in this part of the world, but is increasingly diagnosed with
      the advent of modern imaging techniques and colonoscopy. Two cases of colonic
      diverticula discovered during colonoscopy were highlighted. CASE REPORTS: Case 1-
      This patient was a 79-year old traditional ruler who presented with 2 months
      history of progressive left- sided abdominal pain, dull in nature and sometimes
      colicky but non-radiating. There was no known aggravating or relieving factors.
      There was associated history of chronic constipation dating back to over 15 years
      relieved with use of laxatives. There was no diarrhoea, vomiting or
      haematochezia. He had no history of previous surgeries. Physical examination
      showed mild tenderness at the left iliac fossa. Digital rectal examination was
      normal. Plain abdominal x-ray and abdomino-pelvic ultrasound scan showed no
      abnormalities. Colonoscopy revealed multiple diverticula with diverticulitis at
      the descending and sigmoid colon 40 cm-60 cm from the anal verge. Case 2--This
      patient is a 64-year old retired military officer who presented with constipation
      of 5 years and rectal bleeding of 10 months. Pre-morbid bowel habit was 1-2 bowel
      motions per day but now once in 2 days. Constipation was characterized by
      recurrent passage of hard pellet-like stools. This became associated with passage
      of fresh blood in the stool 10 months ago, and anal pain. Volume of blood was
      about 5 mls per episode, and this occurred only when stool was hard. The anal
      pain was sometimes severe enough to prevent the patient from sitting comfortably
      on both buttocks. There was no weight loss or constipation alternating with
      diarrhoea. He had no history of any chronic medical illness. Colonoscopy revealed
      anal fissure, internal haemorrhoids, and multiple diverticula in the sigmoid and
      descending colon. Both patients are being managed conservatively with dietary
      advice and antibiotics, and still being followed up in the clinic. CONCLUSION:
      Reports of colonic diverticula with diverticulitis in this part of the world are
      few. This is the first report of colonic diverticulosis from Ilorin.

PMID- 23175884
TI  - Principles of chest tube insertion.
AB  - Chest tube insertion is often times a life saving procedure which is well within
      the scope of a trained physician. It is a simple therapeutic manoevre but prone
      to complications if the principles of thoracic drainage are not complied with
      strictly. This article aims to highlight the indications and contraindications
      associated with chest tube insertion and also the technique of thoracostomy tube
      drainage and its associated complications.

PMID- 23175885
TI  - Implementing the new WHO guidelines for the early detection of sensorineural
      hearing loss in newborns and infants in Nigeria.
AB  - This brief educational update examines the key recommendations in the new report
      of the World Health Organisation on newborn and infant hearing screening within
      the Nigerian context. While acknowledging the goal of universal newborn hearing
      screening as desirable, the authors highlight the need for all tertiary hospitals
      in the country to be appropriately equipped to provide at the minimum early
      hearing detection services for all high-risk newborns including those delivered
      by consanguineous parents, those with maternal hypertensive disorders,
      nonelective caesarean section and unskilled birth attendants. In addition to
      conventional risk factors for infant hearing loss, microcephalic and
      undernourished infants should be tested based on evidence from local pilot
      studies. Primary and secondary-level hospitals should maintain an active referral
      system to the tertiary centres within a multidisciplinary framework to assure the
      best of care for the affected infants.

PMID- 23175886
TI  - Hydrocephalus and the eyes: a teaching hospital experience.
AB  - BACKGROUND: The eye developes from prosencephalon, the primitive forebrain and
      hence share similar embryonic origin with brain. This gives insight into primary
      or secondary involvement of eyes in intra-cranial pathology. OBJECTIVE: The study
      was done to describe ocular findings in hydrocephalus patients and effect of
      intervention on the complications. METHODS: Forty one consecutive hydrocephalus
      patients were examined pre and post ventriculo-peritoneal shunts. Comprehensive
      ocular examinations included dilated fundoscopy in all cases. RESULTS: A total of
      41 patients were examined with the age range of between 4 hours to 108 months and
      a mean age of 21 months. Onset of the hydrocephalus varies from 4hours to 108
      months, with a mean of 4.1 weeks. Twenty two patients (51.2%) presented after 2
      months of onset of hydrocephalus. Most common presenting complaint was enlarged
      head seeing in 29 patients (70.7%). CONCLUSION: A total of 12 (30%) out of 41
      patients with hydrocephalus had optic atrophy. Another 10 patients had sun
      setting phenomenon, 3 of these sun-setting phenomena resolved a week after
      ventriculo-peritoneal shunts. The ocular morbidity is high among hydrocephalus
      patients.

PMID- 23175887
TI  - Perinatal mortality in Lagos University Teaching Hospital: a five year review.
AB  - BACKGROUND: An overwhelming proportion of the annual global perinatal deaths
      occur in developing countries. However few data on perinatal mortality are
      available from these countries. Reducing perinatal deaths requires adequate data
      that can be used to develop appropriate strategies. OBJECTIVES: To determine the
      perinatal mortality rate at the Lagos University Teaching Hospital (LUTH), the
      associated risk factors and the causes of perinatal deaths; and make
      recommendations to help reduce perinatal mortality. METHODS: A retrospective
      study of all deliveries in LUTH in the period between January 2002 and December
      2006 was done. Data were collected on all stillbirths and early neonatal deaths.
      Analysis included such variables as booking status, maternal age, parity,
      gestational age, fetal weight and cause of perinatal death. RESULTS: The
      perinatal mortality rate was 70.6/1000 total births. The rate was higher among
      unbooked patients and those with multiple pregnancies. It increased with parity
      after the 2nd delivery and was highest at the extremes of reproductive age
      groups. The commonest causes of death were antepartum haemorrhage, pre
      eclampsia/eclampsia, mechanical causes, intrapartum asphyxia and prematurity.
      CONCLUSIONS: The perinatal mortality rate in our institution is high. The causes
      of perinatal death are largely preventable. Urgent clinical and political actions
      are required to make any progress towards attaining the fourth millennium
      development goal (MDG4).

PMID- 23175888
TI  - Protective role of the methanolic extract of Icacina trichantha on sodium
      arsenite induced genotoxicity and hepatotoxicity.
AB  - BACKGROUND: Arsenic is a toxic metalloid, whose toxicity has raised a lot of
      concern. Humans are exposed to this metalloid through contaminated water, air and
      even foods. As a sulfhydryl reactive metal, arsenic has been found to cause
      extensive damage to organs such as the liver. It has also been found to be a
      potent clastogen, causing DNA damage leading to both benign and malignant tumors.
      OBJECTIVES: The anti-hepatotoxic and anti-genotoxic effects of methanolic leaf
      extract of Icacina trichantha on sodium arsenite induced toxicity in rats were
      determined. METHODS: Oral gavage of sodium arsenite was used to induced
      genotoxicity in rats and micronucleus assay was used to measure the number of
      micronucleated polychromatophilic erythrocytes. The determination of activities
      of serum alanine amino transferase (ALT), aspartate amino transferase (AST) and
      gamma glutamyl transferase (GGT) activities were used for the hepatotoxicity
      assay.. RESULTS: The mean number of micronucleated polychromatophilic
      erythrocytes (MPCE) per 1000 cells +/- SEM from the bone marrow smear was 57.50
      +/- 9.71 in rats treated with both arsenite and extract compared to 129.00 +/-
      16.34 in rats treated with arsenite alone. The serum ALT, AST and GGT activities
      +/- SEM were 67.04 + 3.71, 39.12 +/- 3.45 and 11.54 +/- 0.42 lu respectively for
      the rats treated with arsenite alone. Combined treatment of arsenite and the
      extract significantly decrease (p<0.05) in the activity of the enzymes, 29.75 +/-
      3.43, 15.8 +/- 4.42, 6.87 +/- 0.433 lu for serum ALT, AST and GGT respectively.
      CONCLUSION: The methanolic leaf extract of I. trichantha modulated both the
      hepatotoxic and genotoxic effect induced by sodium arsenite in rats, which
      suggest that Icacina trichantha may serve as a hepatoprotective and anti-tumor
      agent.

PMID- 23175889
TI  - Evaluation of linear dimensional stability of various combinations of dental
      stone and plaster.
AB  - BACKGROUND: It has been observed that due to the cheaper cost of dental plaster
      compared to dental stone, casts on which most of the dental prostheses and
      appliances were being fabricated in various laboratories were often mixtures of
      dental stone and dental plaster in order to reduce production cost. OBJECTIVE: To
      evaluate the dimensional stability of various combinations of Dental Stone and
      Dental Plaster mixtures used to make dental casts. METHODS: Alginate impressions
      of a master model of truncated metal cones were made and casts were produced by
      pouring with various combinations of dental stone and dental plaster mixtures.
      The linear dimensional differences between the inter-abutment distances on the
      casts were measured with an electronic caliper. One sample t-test and percentage
      differences were calculated. RESULTS: Dimensional variations for the distances
      measured using either 50% dental stone or 25% dental stone with plaster were
      statistically significant (p d" 0.05). Mixture of 75% dental stone and 25% dental
      plaster produced casts with no statistically significant dimensional variation
      from the master model (p e" 0.05). CONCLUSION: A mixture of 75% dental stone and
      25% dental plaster could be used for procedures not requiring very accurate
      replica like mounting of teeth for dental training and for study models.

PMID- 23175890
TI  - The antifertility effect of amodiaquine hydrochloride.
AB  - BACKGROUND: A number of antimalarial compounds and herbs have been reported to
      possess antifertility actions. Amodiaquine (AQ) belongs to the same class of
      drugs as chloroquine. Chloroquine has been reported to disrupt the oestrus cycle,
      block ovulation and consequently reduce fertility. OBJECTIVE: This study was
      carried out to investigate the effect of the administration of amodiaquine
      hydrochloride (AQ.HCl) on fertility in the adult cyclic Sprague-Dawley rats.
      METHODS: Thirty cycling female albino rats of Sprague-Dawley strain weighing 120
      g were used in this experiment. They were divided into six experimental groups.
      Groups 1A, 1B and 1C- received peroral (p.o.) 6 mg/kg bw of AQ.HCl, 12 mg/kg bw
      of AQ.HCl and distilled water for 28 days respectively to determine the effect of
      AQ.HCl on the oestrous cycle. Groups 2A, 2B and 2C- received a single dose p.o.
      of 6 mg/kg bw of AQ.HCl, 12 mg/kg bw of AQ.HCl and distilled water at 9 a.m. on
      proestrus respectively to determine the effect of AQ.HCl on ovulation and the
      serum concentrations of follicle stimulating hormone (FSH), luteinizing hormone
      (LH) and prolatin (PRL). RESULTS: AQ.HCl disrupted the oestrous cycle by
      producing a significant (p < 0.05) increase in the diestrus phase and a reduction
      in the other phases when compared with the control. A significant reduction (p <
      0.05) in the number of ova shed on estrus was observed however, there was no
      significant difference in the serum concentrations of FSH, LH and PRL when
      compared with the control. CONCLUSION: Oral administration of AQ.HCl distrupts
      the oestrous cycle and ovulation by increasing the frequency of the diestrus
      phase and reducing the number of ova released at ovulation respectively. These
      events may negatively affect fertility in females of reproductive age.

PMID- 23175891
TI  - The spectrum of malignant neoplasms in Ekiti State, south-west Nigeria.
AB  - BACKGROUND: Geographic pathology is an accepted basis for unravelling trends of
      disease patterns. Proper documentation at the initial stage assists in
      establishing a foundation data. The authors are not aware of a documented pattern
      of malignant neoplasm in Ekiti State. OBJECTIVE: The aim of this study is to
      update the available literature on malignant neoplasms and compare our findings
      with previous work done by other investigators. METHODS: The estimates are based
      on a systematic retrospective survey of cancer cases identified in the Pathology
      Laboratories of Federal Medical Centre, Ido-Ekiti and University Teaching
      Hospital, Ado-Ekiti for the period; January 2002 to December 2009. The data
      recorded on each case were: source of information (histology or cytology), name,
      age, and sex, date of diagnosis and site of tumour. Tumour site and histology
      were coded according to the International Classification of Diseases, ICD-10 for
      presentation in tabular form. RESULTS: A total of 498 cancers were recorded.
      There were 177 (35.5%) males with average age of 54.5 years and 321 (64.5%)
      females with average age of 48.6 years. The estimated Crude Incidence (CI) rates
      for all cancer sites are 14.7 for males and 27.4 for females, per 100,000
      population. In males, the most frequent cancer is prostate cancer (37.9%)
      followed by cancer of the liver (10.7%) and NonHodgkin's Lymphoma, NHL (7.9%). In
      females, the most common cancer is that of the breast (49.3%) followed by the
      cervix (8.5%) and the ovary (5.32%). A total of 28 childhood cancers were
      registered (17 males, 11 females). The most frequent tumours were Burkitt's
      lymphoma (8 cases) and soft tissue sarcomas (3 cases). CONCLUSION: This study
      shows that malignant neoplasms are not uncommon in Ekiti State. There is
      underreporting of cases as the crude incidence rates are low. This study will
      serve as baseline to more population-based studies in future.

PMID- 23175892
TI  - Haemoglobin and ferritin concentrations in cord blood in a tertiary health centre
      in Nigeria.
AB  - BACKGROUND: Haemoglobin(Hb) and serum ferritin (SF) concentrations of cord blood
      of babies born at term at the Lagos State University Teaching Hospital, Maternity
      Centre (Ayinke House), Ikeja in the South-Western part of Nigeria were determined
      to establish mean values for these substances in our locality. OBJECTIVES: To
      establish the mean values for haemoglobin and serum ferritin concentrations of
      cord blood of babies born at term in our environment and to determine the
      prevalence of foetal anaemia and low iron store in cord blood in our locality.
      METHODS: Haemoglobin and ferritin levels in cord blood of 142 newborns were
      determined. Two millilitres of blood was collected from the cord of each newborn
      into EDTA bottle for complete blood count analysis and another 2mls into a plain
      bottle for serum ferritin assay. Cut-off values for cord blood Hb and serum
      ferritin concentrations were 12.5g/dL and 60 microg/L respectively. RESULTS: The
      mean Hb and ferritin values were 13.024 +/- 2.41 g/dL and 70.85 +/- 97.07
      microg/dL respectively. The prevalence of foetal anaemia is 32.4 %. About 59.2%
      of full term newborns had low iron store. Birth weight was significantly
      associated with Hb concentration (p=0.039) and apga sscore (p=0.002). CONCLUSION:
      The prevalence of foetal anaemia was 32.4%. More than half (59.2%) of the
      newborns had low cord blood serum ferritin.

PMID- 23175893
TI  - The Nigeria high glycemic index starchy foods, obesity, and the environment.
AB  - BACKGROUND: Glycemic index has generated a lot of debate for nearly 30 years,
      especially as it relates to the control for the treatment of diabetes.
      OBJECTIVES: This study determined the glycemic index (GI) of ten processed
      Nigerian foods and revealed their similarity in the release of glucose on
      consumption. METHODS: The food items tested were made from yam tubers, cassava
      tubers and local cereals. These foods were served to human volunteers in several
      processed forms which resulted in viscous pastes. RESULTS: The GI results are
      related to the increased incidence of overweight and obesity in the middle class
      Nigerians. CONCLUSION: It is suggested that these processed foods should be
      discouraged in the regular dietary plan if Nigerians desire to stay slim and save
      the planet by reducing carbon emission and climate change.

PMID- 23175894
TI  - The assessment of plasma ascorbic acid, alpha tocopherol and albumin creatinine
      ratio in patients with chronic renal failure.
AB  - BACKGROUND: Albumin: creatinine ratio is used to assess chronic renal damage
      while the status of Antioxidant vitamins could be compromised in chronic renal
      failure patients. OBJECTIVE: To assess the levels of Antioxidant vitamins and
      Albumin creatinine ratio, in patients with chronic renal failure. (CRF) METHODS.
      Thirty patients (15 males, 15 females), aged 17-80 years old diagnosed as having
      chronic renal failure but clinically stable were recruited from the University of
      Benin Teaching Hospital. The control subjects were apparently healthy
      individuals. Blood and urine samples were collected for antioxidant Vitamin C and
      E, albumin and creatinine assays respectively. RESULTS: Plasma vitamin E level
      significantly decreased ( p < 0.05) while Plasma vitamin C showed no significant
      difference (p > 0.05), in chronic renal failure patients when compared to the
      control subjects. Albumin creatinine ratio was significantly increased ( p <
      0.05) compared to the control groups CONCLUSION: There are reduced levels of
      plasma antioxidant vitamins C and E in patients with chronic renal failure. These
      findings suggest that supplementation with antioxidant vitamins C and E could be
      beneficial to slow down the process of progressive renal damage in CRF. However
      we advice that more interventional studies be carried out on a larger scale to
      truly establish the beneficial effects of antioxidant supplementation in CRF
      patients.

PMID- 23175896
TI  - Basic arthroscopy: a review paper.
AB  - Arthroscopy is a key hole surgical procedure that is used to visualized,
      diagnosed and treat pathologies inside a joint. Though it offers numerous
      advantages, it is technically demanding and requires a learning curve. Moreso,
      its uses in making diagnosis and therapeutic interventions are rewarding.
      However, the procedure is not yet widely practiced in our sub-region. This review
      to bring to fore the advantages of arthroscopic procedures, the indications and
      contraindications and to stimulate interest of these procedures in our sub region
      The literature materials on arthroscopic procedures were reviewed The era of
      extensive opening of joint for surgical procedure is coming to an end. The use of
      arthroscopic procedures in management of patients will improve the quality of
      care received by the patients. This review is to stimulate interest of
      arthroscopy in our sub-region.

PMID- 23175895
TI  - Effects of ethanolic extract of Tetrapleura tetraptera fruit on serum lipid
      profile and kidney function in male Dutch-white rabbits.
AB  - BACKGROUND: Tetrapleura tetraptera fruit is widely used in Nigeria as a spice and
      for treatment of various medical ailments. Reports indicate that feeding of
      extracts to animals produced some toxic effects and pathological lesions in some
      organs. OBJECTIVE: This study was designed to investigate the effects of 10 days
      oral administration of the ethanolic extract of Tetrapleura tetraptera (TTE) on
      the lipid profile and kidney function in male rabbits. METHODS: Twenty healthy,
      acclimatized male rabbits weighing 1.4 - 1.6 kg were randomly divided into four
      groups. Group 1 served as control and received only water while groups 2, 3 and 4
      were administered 50, 100 and 150 mg/kg bodyweight of TTE respectively. Fasting
      serum from all groups were analyzed for lipid profile and kidney function
      parameters using standard protocols. Data were analyzed using student's t-test
      and ANOVA. RESULTS: Tetrapleura tetraptera extract elicited reduction in serum
      triacylglycerols, elevation of LDL-cholesterol and alteration of kidney function
      parameters in male rabbits. CONCLUSION: Ethanolic extract of Tetrapleura
      tetraptera may predispose to hypertension and cardiovascular diseases.

PMID- 23175897
TI  - Chest X- ray findings in HIV patients in relation to the CD4 count.
AB  - BACKGROUND: CD4 count measures the degree of immunosupression in HIV-infected
      patients. Immunosupression results in lack of ability of the body to fight
      infections thus predisposing the individual to infection; lung is one of the most
      susceptible organs. An important diagnostic tool in assessing the respiratory
      complications as well as the manifestations of HIV infection is the chest
      radiograph. OBJECTIVE: This study is aimed at determining the radiological
      features seen on chest radiographs of HIV/AIDS patients in relation to their
      corresponding CD4 count which is a measure of immunosupression. METHODS: This
      study was conducted at Lagos State University Teaching Hospital (LASUTH) HIV
      clinic between September 2009 and August 2010 amongst all consenting registered
      HIV/AIDS patients. A total of one hundred and six consenting participants were
      recruited consecutively into the study, their blood samples were collected for
      CD4 count assay, and all the participants were sent for chest xray in the
      radiology department. They were asked to fill the structured questionnaire to
      obtain demographic data. RESULTS: More than three-quarters, 87(82.1%) had a
      normal chest radiographs. The abnormal findings included 13 cases of (12.3%)
      pulmonary tuberculosis, 3(2.8%) having bronchopneumonia, and 3(2.8%) lobar
      pneumonia. Majority, 32 of 87 of those with normal chest-x ray had CD4 count <100
      cells/il while about half of the patients with pulmonary tuberculosis (5 of 13)
      had CD4 count >350 cells/il. All the three patients who had lobar pneumonia had
      CD4 count between 200-350 cells/il, while 2 of 3 patients with bronchopneumonia
      had CD4 counts between 200-350 cells/il, only 1 of them had CD4 of 100-200
      cells/il CONCLUSION: About three-quarters of HIV-infected patients had normal
      chest radiographs, majority of those with normal chest x-ray were severely
      immunocompromised. While almost half of those with pulmonary tuberculosis had CD4
      count >350 cells/il. The CD4 count level may not be an indicator of pulmonary
      infection.

PMID- 23175898
TI  - A 5-year retrospective audit of orthodontic services in a tertiary hospital.
AB  - BACKGROUND: Orthodontics became a recognized specialty of dentistry in Nigeria
      about four decades ago with the provision of services at the Orthodontic Unit of
      Lagos University Teaching Hospital, Lagos. OBJECTIVE: The study reviewed and
      appraised the orthodontic services provided at the Orthodontic Unit of the Lagos
      University Teaching Hospital, Lagos over a five-year period. METHOD: A
      retrospective study of first visit patients with various malocclusions seen at
      the Orthodontic Unit of Lagos University Teaching Hospital, Lagos, Nigeria
      between September 2000 and August 2005 was conducted. The demographic data, date
      of presentation, presenting malocclusion, referrers for each patient, and types
      of orthodontic treatment received and where referred for further treatment were
      recorded. RESULTS: A total of 512 first visit patients were seen during the study
      period under review.There were 292 (57.0%) females and 220 (43.0%) males, with an
      age range of 3 months to 41 years and a mean age of 14.65 +6.43 years (S.D).
      Majority of the patients were in the 11-20 years age group (n=266, 52.0%).
      Angle's Class I malocclusion was the most common problems seen (n=360, 72.0%). Of
      all the patients seen, the primary concern was on their teeth arrangement which
      was found to be unsatisfactory in 273, 53.3% patients. There was increased
      awareness of their problems and this led about 44% of the study group to seek
      orthodontic treatment on their own. Fixed upper and lower appliances were the
      most common types of appliances used at the centre (n=265, 51.8%). Out of 246
      patients who benefitted from one form of interdisciplinary treatment or the
      other, Oral and Maxillofacial Surgery and Paediatric Dentistry departments
      treated 39.8% and 31.7% respectively. CONCLUSION: Angle's Class I malocclusion
      appeared to be the most common malocclusion among the patients seen. Patients
      seen during the study period were more aware of their need for treatment and
      fixed upper and lower appliances were mostly used. The low referral by doctors
      was observed. There is a need to better integrate more basic dental skills in the
      training of the medical students. The information obtained in the study will help
      with future manpower development, teaching, further research and improvement in
      services provided at the hospital.

PMID- 23175899
TI  - Antidiarrhoeal activity of DAS-77 (a herbal preparation).
AB  - BACKGROUND: DAS-77 is a traditional herbal preparation composed of the young
      callous bark of mango (Mangifera indica Linn., Anacardiaceae) and the dried root
      of pawpaw (Carica papaya Linn., Caricaceae). This phytomedicine is claimed to
      have beneficial effects in the treatment of gastrointestinal disorders, including
      diarrhoea. OBJECTIVE: To investigate the antidiarrhoeal effect of DAS-77 using
      standard pharmacological models. METHODS: Normal and castor oil-induced
      intestinal transit, and castor oil-induced diarrhoea tests wore carried out in
      mice while intestinal fluid accumulation and gastric emptying tests were carried
      out in rats. Acute toxicity test and preliminary phytochemical analysis were also
      conducted. RESULTS: The results obtained in this study revealed that DAS-77 had
      no significant inhibitory effect on normal intestinal transit, castor oil-induced
      diarrhoea, intestinal fluid accumulation and gastric emptying. However, the
      inhibitory effect of DAS-77 was significant (p<0.001) relative to control in the
      castor oil-induced intestinal transit test. Peak effect was produced at the dose
      of 100 mg/kg (p.o.). The effect of DAS-77 in this respect was reversed by
      pilocarpine and propranolol, but not by phenoxybenzamine. DAS-77 did not produce
      any mortality given p.o. up to 10 g/kg, indicating the relative safety of the
      preparation. The i.p. LD50 was estimated to be 1122 mg/kg. The remedy was found
      to contain saponins, tannins, phenols and alkaloids. CONCLUSION: Findings in this
      study suggest that DAS-77 possesses antidiarrhoeal activity due to the inhibition
      of intestinal motility possibly mediated by muscarinic and alpha adrenergic
      receptors.

PMID- 23175900
TI  - Implementing the new WHO guidelines for the early detection of sensorineural
      hearing loss in newborns and infants in Nigeria.
AB  - This brief educational update examines the key recommendations in the new report
      of the World Health Organisation on newborn and infant hearing screening within
      the Nigerian context. While acknowledging the goal of universal newborn hearing
      screening as desirable, the authors highlight the need for all tertiary hospitals
      in the country to be appropriately equipped to provide at the minimum early
      hearing detection services for all high-risk newborns including those delivered
      by consanguineous parents, those with maternal hypertensive disorders,
      nonelective caesarean section and unskilled birth attendants. In addition to
      conventional risk factors for infant hearing loss, microcephalic and
      undernourished infants should be tested based on evidence from local pilot
      studies. Primary and secondary-level hospitals should maintain an active referral
      system to the tertiary centres within a multidisciplinary framework to assure the
      best of care for the affected infants.

PMID- 23175901
TI  - Trends in maternal mortality at the Lagos University Teaching Hospital, Lagos,
      Nigeria.
AB  - BACKGROUND: Recent reports suggest that the burden of maternal mortality remains
      heavy in Sub-Saharan Africa; and that the fifth millennium development goal might
      not be achieved. As the target date 2015 draws near, we carried out a review of
      maternal mortality in a Teaching Hospital unitto assess the current situation.
      OBJECTIVES: To determine the Maternal Mortality Ratio (MMR), the clinical causes
      of maternal deaths and the numerical and etiological trends in maternal mortality
      at the Lagos University Teaching Hospital (LUTH). METHOD: The records of births
      and maternal deaths at LUTH over a five year period were reviewed. The data
      collected was analyzed to determine the maternal mortality ratio, the socio
      biological factors associated with maternal death and the clinical causes.
      Comparisons are made with findings from previous studies done in LUTH and
      elsewhere. RESULTS: The maternal mortality ratio was 2096 per 100000 live births.
      The mortality ratio has more than doubled over a period of 3 decades. Unbooked
      patients accounted for 7.1% of deliveries but contributed 88.1% of the maternal
      deaths.Majority (59.0%) of the deaths occurred within 24 hours of admission. The
      main clinical causes of death included sepsis (17.9%), hypertensive diseases
      (17.9%), abortion (11.2%), HIV/AIDS infection (11.2%)), haemorrhage (9.0%) and
      medical disorders (18.7%). CONCLUSION: The maternal mortality ratio remains high
      in our unit in line with some other reports from Nigeria but in contrast to the
      trends in other developed and developing countries. Unless urgent action is
      taken, the 5th millennium development goal may not be achieved.

PMID- 23175902
TI  - Multiple gestations/pregnancies from IVF process in a fertility center in
      Nigeria, 2009-2011: implementing policy towards fewer (double and single) embryo
      transfer.
AB  - BACKGROUND: Infertility is a major problem in Nigeria, which has caused many
      couples to be burdened with physical, psychological and social issues. IVF (In
      vitro fertilization) has played a major role in reducing the burden among
      infertile couples. However, despite the role of IVF in solving infertility in
      Nigeria, it is important to address the issue of rising rates of multiple births
      from IVF. Also to create a balance between the number of embryo transferred and
      easing the burden couples face from infertility. OBJECTIVE: To determine the
      trend/rate in multiple gestations from IVF, identify possible factors responsible
      and proffer ways to reduce multiple gestation rates. METHODS: We did a case
      series review from 2009-2011 of IVF cycles performed at a private clinic with an
      academic setting in Nigeria. Our primary outcome of interest was multiple
      gestations/pregnancies All patients identified with outcome of interest, were
      included in the study sample. We reviewed the IVF process of each patient using
      medical records from pre-evaluation to clinical pregnancy confirmed by
      ultrasound. We reported the multiple gestation trend/rate. RESULTS: 25 women with
      the mean age of 39.9 +/- 7.3 years had multiple pregnancies from 2009 to 2011. Of
      the 25 women, 24% of the pregnancies, occurred in 2009, 40% occurred in 2010 and
      36% in 2011. In 2009, 83% of the pregnancies were twin gestations and 17%
      triplets. In 2010, 40% were twin gestations, while triplet, quadruplet and
      quintuplet gestations were 20% each. In 2011, 66% were twin gestations and 34%
      quadruplet gestation. The factors we identified that could have lead to an
      increase in multiple gestations from 2009-2010 included improvement in pre
      evaluation work up, stimulation protocol, efficacy of the IVF lab and mean of 5
      embryos transferred. In 2011, embryo transferred was reduced to 3-4. From 2009 to
      2011, mean number of embryos transferred was 4.2 (95% CI: 3.87-4.47). CONCLUSION:
      Multiple gestations and associated risk from IVF in Nigeria can be reduced by
      reduction in number of embryos transferred and possibly by improvement in
      practice process. As the IVF process becomes more efficacious, fertility centres
      in Nigeria will not need to transfer up to 4 embryos in order to have a positive
      pregnancy; and as a result they can move towards two to single embryo transfer.

PMID- 23175903
TI  - Oral administration of vitamin C and vitamin E ameliorates lead-induced
      hepatotoxicity and oxidative stress in the rat brain.
AB  - BACKGROUND: Lead toxicity is a public health concern. Lead is one of the
      dispensable and non-biodegradable heavy metals and is toxic even at low
      concentrations. OBJECTIVE: This study was to investigate the effect of oral
      administration of Vitamin C and Vitamin E on lead-induced hepatotoxicity and
      oxidative stress in the brain of rats. METHODS: Thirty Sprague-Dawley albino male
      albino rats (115.58 +/- 4.96g) were divided equally into five groups. The rats
      were fed rat chow and water ad libitum. Group 1 rats served as control and were
      orally administered 2ml saline every day for 7 weeks. Group 2 rats received
      orally 2ml lead acetate solution (60mg/kg body weight) every day for 7 weeks.
      Group3 rats received orally 2ml lead acetate solution (60mg/kg body weight) and
      vitamin C (40mg/kg body weight) every other day for 7 weeks. Group 4 rats
      received orally 2ml lead acetate solution (60mg/kg body weight) and vitamin E
      (150mg/kg body weight)every day for 7weeks. Group 5 received orally lead acetate
      solution at 60mg/kg body weight and vitamin C (40mg/kg body weight)and vitamin E
      (150mg/kg body weight) every other day for 7weeks. Three rats from each group
      were sacrificed after the fourth week. The remaining rats were sacrificed after
      the seventh week. Changes in body weight, liver weight, brain weight, activities
      of liver function enzymes (aspartate amino transferase (AST), alanine amino
      transferase (ALT) and alkaline phosphatase(ALP) in the serum at week 4 and week 7
      were assayed.The oxidative stress markers (reduced glutathione (GSH), nitric
      oxide(NO), malondialdehyde(MDA), levels, catalase(CAT) and superoxide dismutase
      (SOD) activities) were determined in the brain of rats. Serum lead level of rats
      was also determined. RESULTS: The lead Pb exposed rats caused a significant
      (p<0.01) increase in bioavailable lead in the blood (p<0.05) as compared to the
      control. AST, ALT and ALPactivities were significantly increased (p<0.05) in the
      serum of rats exposed to lead as compared to the control. NO and MDA levels were
      significantly increased (p<0.05) in the brain of rats exposed to lead, while GSH
      level, SOD and CAT activities were significantly reduced (p<0.05) in the brain of
      rats exposed to lead when compared with the control. CONCLUSION: Data of the
      study indicate that oral administration of vitamin C and vitamin E significantly
      reduced the blood lead concentration, ameliorates the hepatic damage and
      significantly reduced the oxidative stress in the brain of rats.

PMID- 23175904
TI  - Intravesical migration of a failed and forgotten intrauterine contraceptive
      device after 20 years of insertion--a case report.
AB  - Intrauterine contraceptive device (IUCD) is a commonly utilized reversible
      contraceptive technique especially in the developing world. Though effective, it
      is not immune to complications. Migration of the device is a rare but serious
      complication which may be symptomatic or asymptomatic. We report a case of a 45yr
      old woman who had IUCD inserted 20 years earlier and had forgotten about it since
      she subsequently had three full term pregnancies leading to successful vaginal
      deliveries. The forgotten IUCD was discovered incidentally during evaluation of
      the woman for haematuria as it had migrated to the wall of the bladder. The case
      is reported to increase index of suspicion as detailed clinical history is
      important in evaluating cases of haematuria.

PMID- 23175905
TI  - The perception of caregivers attending a Nigerian teaching hospital on teething.
AB  - BACKGROUND: in November 2008. There was a national tragedy which recorded about
      eighty four Nigerian infant deaths due to the consumption of adulterated teething
      syrup- 'my pikin' administered to children by mothers to prevent 'teething
      problems". This could have been prevented if they had been well informed about
      the teething process. OBJECTIVE: to determine the knowledge, understanding and
      beliefs of caregivers attending LASUTH immunization clinic about teething.
      METHODS: An interviewer administered questionnaire was used to collect data from
      260 caregivers of children aged 4-36 months attending the immunization clinic in
      LASUTH over a six weeks period. The questionnaire assessed their knowledge,
      understanding, beliefs about teething and the teething experience in their wards.
      RESULTS: The mean age of the respondents was 30.4 5.3years. Fifty seven percent
      had tertiary education. However, none of the caregivers obtained information
      about teething from the dentist. There was an association between educational
      level and attitude to teething (p=0.002) as well as their understanding of the
      teething process (p=0.0009). Gum irritation was the most reported symptom
      observed in this study. Many of the caregivers had erroneous beliefs regarding
      the systemic symptoms such as fever, diarrhoea and vomiting which they attributed
      to teething. CONCLUSION: Many of the caregivers studied still had erroneous
      beliefs regarding teething. Thus there is a need to disseminate the right
      information about teething to care givers in this environment in order to
      discourage the use of the term "teething" for a serious childhood illness that
      might require prompt medical attention.

PMID- 23175906
TI  - Relationship between spasticity and health related quality of life in individuals
      with cerebral palsy.
AB  - BACKGROUND: There is growing awareness of health related quality of life in
      cerebral palsy patients, though there is paucity of data in determining its
      relationship with spasticity in cerebral palsy patients. OBJECTIVE: The purpose
      of this study was to determine the relationship between spasticity and health
      related quality of life in cerebral palsy patients. METHOD: A cross-sectional
      survey design was employed in this study. A total of fifty individuals with
      cerebral palsy, males (54%) and females (46%) within the age range of 5 years and
      18 years (9.06 +/- 3.38 years) participated in the study. Measurement of
      spasticity was done by the researcher using the Modified Ashworth Scale (MAS) and
      the parents or primary caregivers of the participants were required to complete
      the Caregiver Priorities and Child Health Index of Life with Disabilities
      (CPCHILD) questionnaire, which is a 37-item questionnaire that collects
      information on the health related quality of life. Data was analysed separately
      for each of the six domains of the questionnaire using the Pearson Product-Moment
      Correlation coefficient on SPSS version 17 and the level of significance was set
      at p=0.05. RESULTS: According to the results, the domains of comfort and emotions
      with communication and social interaction do not have an influence on spasticity.
      The results also revealed that there was a significant relationship between
      spasticity and health related quality of life in cerebral palsy patients
      (p=0.01). CONCLUSION: Personal care and mobility which are aspects of the health
      related quality of life should be paid more attention to, as they are negatively
      affected by spasticity in patients with cerebral palsy.

PMID- 23175907
TI  - The incidence of electrolyte and acid-base abnormalities in critically ill
      patients using point of care testing (i-STAT portable analyser).
AB  - BACKGROUND: Electrolytes and acid-base disorders are common challenges seen in
      the intensive care unit (ICU) resulting in difficulty in weaning patients off the
      ventilator, prolonged admission periods, preventable cardiac arrhythmias and
      cardiac arrest. These require prompt lab results most of which are done serially,
      ideally a point of care test (POCT), as most central hospital lab result's
      turnaround time (TAT) sometimes might not meet up with the urgency of clinical
      decision making in the ICU. OBJECTIVE: To determine the incidence of electrolytes
      and acid-base abnormalities using i-Stat portable analysers in the ICU of the
      Lagos University Teaching Hospital (LUTH). METHOD: The i-STAT Portable Clinical
      Analyzer, a POCT system consisting of a hand-held analyzer and single-use
      cartridges that measure different panels of analytes in 65-100 microl of blood
      using an EC8+ cartridge type analyzer for sodium, potassium, chloride, urea,
      glucose, pH, blood gases [TCO2, pO2, pCO2]) and heamatocrit was used. RESULTS:
      Over 66.78% of the patients had multiple electrolytes and acid-base
      abnormalities. Azotemia in 20%, hypoglycaemia in 13.33%, and hyperglycaemia in
      53.33% of patients. CONCLUSION: it is concluded from this study that electrolyte
      and acid base abnormalities is not uncommon in the intensive care unit of LUTH
      and the i-STAT Portable Clinical Analyzer was helpful in facilitating early
      diagnosis and treatment.

PMID- 23175908
TI  - Clinicohistopathological analysis of 5 Nigerian cases of malignant fibrous
      histiocytoma of the jaws.
AB  - BACKGROUND: Malignant fibrous histiocytoma (MFH), is a soft tissue sarcoma that
      occurs predominantly in the soft tissue of the extremities. It rarely occurs in
      facial bones. Few cases in the jaws have been reported. OBJECTIVE: To report and
      review the relevant clinicopathologic features of 5 cases of jaw MFHin Nigerians.
      METHODS: All cases in the records of the Department of Oral Pathology of the
      Lagos University Teaching Hospital which were histologically diagnosed as MFH
      were retrieved. Hematoxylin and eosin slides of cases were re-examined to confirm
      diagnosis. Information retrieved included age, sex, location, x-ray, estimated
      duration, recurrence, and histological presentation. Data was analyzed using SPSS
      statistical package. RESULTS: Age ranged between 12-42 years with a male sex
      predilection (3 cases/60.0%) and sole maxillary site predilection (5
      cases/100.0%). Estimated duration of lesion ranged from 2 -12 months. Two cases
      recurred post surgical treatment. All cases presented as the storiform
      pleomorphic type with one case presenting with a delicate/scanty connective
      tissue stroma. Chronic inflammation was scanty in the two cases that recurred.
      CONCLUSION: MFH of the jaws is rare among Nigerians. Its clinico radiological
      presentation maymimick other more aggressive or less benign lesions of the jaws
      thereby resulting in misdiagnosis and in appropriate patient management.

PMID- 23175909
TI  - X-ray pelvimetry and labour outcome in term pregnancy in a rural Nigerian
      population.
AB  - BACKGROUND: X-ray pelvimetry is a radiological investigation that involves the
      measurement of different anthropometric dimensions of the pelvis. The pelvic
      inlet and outlet play important role in labour outcome. The query as to whether x
      ray pelvimetry has a useful predictive value regarding labour outcome prompted
      this study. OBJECTIVES: To determine whether the use of X-ray pelvimetry is still
      relevant in term pregnancy, and its reliability in predicting labour outcome.
      METHOD: This was a retrospective study of pregnant patients who had X-ray
      pelvimetry at term and successfully delivered at a rural community based mission
      maternity hospital between 2005-2008. Each x- ray pelvimetry report was matched
      with the mode of delivery of the patient. 150 patients who were found suitable
      had data such as age, mode of delivery, etc, extracted. RESULTS: In a review of
      150 X -ray pelvimetry films, 119 (79.33%) were categorised as adequate pelvis,
      10(6.67%) borderline pelvis and 21 (14%) inadequate pelvis respectively based on
      the conclusions of the radiologist. Out of the 21 patients with inadequate
      pelvis, 14 (67%) had normal delivery and 7 (33%) had caesarean section. For the
      10 patients with borderline pelvis, 7 (67%) had normal delivery and 3 (33%) had
      caesarean section. CONCLUSION: This study has demonstrated that X-ray pelvimetry
      may not be accurate but has fair predictive value on mode of delivery in term
      pregnancy.

PMID- 23175910
TI  - Hearing loss due to wax impaction.
AB  - BACKGROUND: Deafness and hearing impairment are major causes of disability in
      developing countries. The World Health Organization (WHO) has pointed out that
      much deafness and hearing impairment is avoidable or remediable. A good
      proportion of patients presenting in the Ear, Nose, Throat, Head and Neck
      (E,N,T,H &N) Surgery Clinic of the University of Benin Teaching Hospital
      (UBTH),Benin City, have ear wax impaction causing hearing loss. OBJECTIVE: This
      study was therefore carried out to determine the prevalence of wax impaction
      among the aetiological factors for hearing loss, the type and severity of hearing
      loss due to wax impaction in our hospital. METHODS: Patients who met the
      inclusion criteria for the study were enrolled and Pure Tone Audiometry (PTA)
      threshold for each ear with wax impaction was determined at 250Hz, 500Hz, 1KHz,
      2KHz, 4KHz and 8KHz by air conduction, Also bone conduction measurements were
      obtained at 500Hz, 1KHz, 2KHz and 4KHz. RESULTS: Forty-two out of 471 ears with
      hearing loss had wax impaction in this study; giving a prevalence of 8.9% for wax
      impaction among the aetiological factors for hearing loss. The result showed that
      mild hearing loss was the average and predominant type of hearing loss in terms
      of severity. Pure tone audiograms showed conductive hearing loss in all the
      patients, while 8 out of the 42 ears had a super-imposed sensorineural component,
      which gave a mixed hearing loss forthe ears. CONCLUSION: Wax impaction is a
      relatively common cause of hearing loss, usually of the mild conductive type.
      Appropriate strategies should be put in place for its management.

PMID- 23175911
TI  - Peri-operative deaths associated with ear, nose, throat, head and neck surgeries:
      a ten-year prospective survey.
AB  - BACKGROUND: Apart from severe psychological effect on members of the health team
      involved, peri-operative deathcan also have far reaching effects on the surgeon,
      hospital and the community. Peri-operative death has also been categorized as
      being avoidable and non-avoidable. OBJECTIVE: This study was therefore carried
      out to identify the factors that led to peri-operative deaths in our practice,
      with the aim of proferring preventive strategies. METHODS: All cases of peri
      operative deaths associated with ear, nose, throat, head and neck(ENTH&N)
      surgeries in the University of Benin Teaching Hospital (UBTH),Benin city, between
      January, 2001 and January, 2011 were prospectively surveyed. RESULTS: There were
      6 peri-operative deaths out of a total of 1,138 recorded ear, nose, throat, head
      and neck surgeries in the UBTH during the study period. This gives a peri
      operative mortality rate of 0.53% for ENTH & N surgeries. Most of the peri
      operative deaths were associated with advanced head and neck cancers,
      tracheostomies and emergency procedures. Inexperience on the part of resident
      anaesthetists and surgeons, non-availability of critically needed blood and poor
      training of health personnel on post-tracheostomy patient management, were the
      main factors identified in the causation of the peri-operative deaths.
      CONCLUSION: Close supervision of residents by consultants, proper hospital
      funding and the requisite training of all health personnel are the recommendation
      to prevent these tragedies.

PMID- 23175912
TI  - Effects of dance movement therapy on selected cardiovascular parameters and
      estimated maximum oxygen consumption in hypertensive patients.
AB  - BACKGROUND: Objective:Arterial hypertension is a medical condition associated
      with increased risks of of death, cardiovascular mortality and cardiovascular
      morbidity including stroke, coronary heart disease, atrial fibrillation and renal
      insufficiency. Regular physical exercise is considered to be an important part of
      the non-pharmacologictreatment of hypertension. OBJECTIVE: The purpose of this
      study was to investigate the effects of dance movement therapy (DMT) on selected
      cardiovascular parameters and estimated maximum oxygen consumption in
      hypertensive patients. METHODS: Fifty (50) subjects with hypertension
      participated in the study. They were randomly assigned to 2 equal groups; A (DMT
      group) and B (Control group). Group A carried out dance movement therapy 2 times
      a week for 4 weeks while group B underwent some educational sessions 2 times a
      week for the same duration. All the subjects were on anti-hypertensive drugs. 38
      subjects completed the study with the DMTgroup having a total of 23 subjects (10
      males and 13 females) and the control group 15 subjects (6 males and 9 females).
      Descriptive statistics of mean, standard deviation and inferential statistics of
      paired and independentt-testwere used for data analysis. RESULTS: Following four
      weeks of dance movement therapy, paired t-test analysis showed that there was a
      statistically significant difference in the Resting systolic blood pressure
      (RSBP) (p < 0.001*), Resting diastolic blood pressure (RDBP) (p < 0.001*),
      Resting heart rate (RHR) (p = 0.024*), Maximum heart rate (MHR) (p=0.002*) and
      Estimated oxygen consumption (VO2max) (p = 0.023*) in subjects in group A (p <
      0.05) while there was no significant difference observed in outcome variables of
      subjects in group B (p > 0.05). Independent t-test analysis between the
      differences in the pre and post intervention scores of groups A and B also showed
      statistically significant differences in all the outcome variables (p <0.05).
      CONCLUSION: DMT was effective in improving cardiovascular parameters and
      estimated maximum oxygen consumption in hypertensive patients.

PMID- 23175913
TI  - Tuberculate supernumerary teeth: report of a case showing typical and atypical
      features and the management.
AB  - Tuberculate supernumerary teeth are found in the maxillary anterior region. They
      usually result in oral problems such as malocclusion, food impaction, poor
      aesthetics and cyst formation. There is paucity of literature on this anomaly in
      our environment. This paper describes a case of tuberculate supernumerary teeth
      with typical and atypical features of supernumerary teeth in this region.
      Treatment is carried out with a combination of surgical and orthodontic methods.
      Early diagnosis and treatment of this anomaly is suggested to avoid more serious
      consequences and to prevent severe orthodontic complications.

PMID- 23175914
TI  - Sharp injuries among hospital waste handlers.
AB  - BACKGROUND: Health care workers are generally predisposed to injuries from sharps
      as a health hazard. This is more pronounced among waste handlers. OBJECTIVE: It
      is therefore important to assess these injuries among this group of people with a
      view to identifying the risk factors and suggesting preventive methods. METHODS:
      Questionnaires were administered to People handling wastes in our hospital to
      assess their level of education on injury prevention, immunization status and
      preventive methods used by them to prevent these injuries and subsequent
      infections. RESULTS: Forty three waste handlers were interviewed. Twenty eight
      (65.8%) of them received training before commencing on the job while 14 (32.5%)
      never received any training. Only thirty nine (90.7%) of them always use hand
      gloves before carrying wastes. Only three (7.0%) of the respondents have been
      screened for Hepatitis B, 19 (44.2%) for HIV, while 10 (23.3%) were screened for
      Hepatitis B, C, and HIV. Eleven (25.6%) of them have been injured with sharps.
      The finger was the most injured in 7 (93%) of them. CONCLUSION: Training and re
      training of health workers is important and should be encouraged. All health
      workers should have pre-employment immunization against Hepatitis B, C as well as
      other before commencing on their jobs. Workers should be screened for infective
      diseases that can be of legal problem while at the job and the workers should be
      effectively immunized.

PMID- 23175916
TI  - PLIVA v. Mensing: generic consumers' unfortunate hand.

PMID- 23175915
TI  - Minimising corneal scarring from the use of harmful traditional eye remedies in
      developing countries.
AB  - Corneal scarring is the fourth largest cause of blindness globally, and a much
      more prominent factor in developing countries. Blindness from corneal scarring is
      largely a preventable phenomenon, and is capable of causing significant morbidity
      that can last for a lifetime. A significant proportion of these cases are caused
      by the use of harmful traditional eye medicines/remedies, and are used and
      prescribed by friends, relatives and traditional healers, with widespread use
      especially in developing countries. Use of traditional remedies can also cause
      harm indirectly by causing delays before seeking medical treatment. Reducing
      corneal scarring from the use of harmful traditional medicine is through a
      combination of approaches with the key strategies being community diagnosis,
      education, participation, and intervention, with provision of basic eye care
      integrated into the primary health care of the community. Collaboration with
      traditional healers in the community is also another approach that has been found
      to be useful.

PMID- 23175917
TI  - The right to be fat.

PMID- 23175918
TI  - Tipping the scale: a place for childhood obesity in the evolving legal framework
      of child abuse and neglect.

PMID- 23175919
TI  - The devil (and drugs) in the details: Portugal's focus on public health as a
      model for decriminalization of drugs in Mexico.

PMID- 23175920
TI  - How to prepare a scientific surgical paper. A practical approach.

PMID- 23175921
TI  - The Todani classification for bile duct cysts: an overview.
AB  - Bile duct cysts are a rare medical condition and are more frequent in children.
      However, the disease is becoming increasingly common in adults. The modified
      Todani classification, which is based on anatomical characteristics, is the
      current standard classification method. However, this classification does not
      take the following factors into consideration: different epidemiology,
      pathogenesis, risk of malignant transformation, clinical and imaging aspects, and
      different therapeutical approaches for all the bile duct cysts. Thus, some
      clinicians denied its clinical significance and viability. Moreover, some rare
      variants (i.e., cystic duct cysts) of bile duct cysts were initially not included
      and were subsequently categorized as type VI. Although it clusters different
      diseases, the Todani classification of bile duct cysts should also be used in
      clinical practice because it is simple, reproducible and widely agreed upon,
      thereby allowing an appropriate comparative analysis between different series of
      patients who are classified based on this scheme. Exceptional, cystic duct cysts
      should be included in the Todani classification (as a subtype of type II BDC
      rather than as a "new" type VI) so that the gastroenterologists, radiologists and
      surgeons are aware of this variation.

PMID- 23175922
TI  - Clinico-epidemiological study of caustic substance ingestion accidents in
      children in Anatolia: the DROOL score as a new prognostic tool.
AB  - BACKGROUND: To examine the clinico-epidemiological details of paediatric caustic
      substance ingestion (CSI) accidents in Turkey. To present the new DROOL Score
      (DS), which the authors developed based on the severity and duration of initial
      signs and symptoms (ISSs) to predict oesophageal stricture (OS) without
      endoscopy, and to present our management protocol based on immediate feeding,
      early detection, and oesophageal balloon dilatation (OBD) of OS with no barium
      study. METHODS: We prospectively reviewed the records of 202 children admitted
      with a history of CSI within 48 hours. Patient, parent, caustic substance, and
      accident characteristics were noted in detail. Patients were fed as soon as they
      could swallow saliva. Diagnoses of OS were made earlier via timely endoscopy
      (mean, 10-14 days after CSI) for patients with persistent dysphagia and OBD was
      started earlier. ISSs and DSs were analyzed. OS treatment results were compared
      between early (10-14 days) and late (> or = 21 days) dilatation patients who were
      referred for OBD by other hospitals. RESULTS: In total, 144 (71%) incidents
      occurred within the parents' home and 44 (22%) occurred at another individual's
      home. The caustic substances were frequently sold in non-original containers
      (68.8%). Most patients' parents had low incomes and were poorly educated. Ninety
      six children had no ISSs, whereas 106 patients had ISSs. Seventeen symptomatic
      patients had persistent dysphagia after 10-14 days. Timely endoscopy was
      performed within 10-14 days for these patients only, and OS was diagnosed and
      successfully treated. DSs were significantly lower in patients with OS than those
      without (p < 0.001). A DS < or = 4 was a significant predictor of OS (100%
      sensitivity, 96% specificity, 85% positive and 100% negative predictive values).
      Results were significantly more satisfactory in early (n = 17) than in late (n =
      6) dilatation patients. CONCLUSIONS: Paediatric CSI accidents might decrease if
      caustic substances were sold in the original child-proof containers. OS can be
      highly predicted by a simple DS instead of endoscopic grading, and can be
      diagnosed earlier (10-14 days) via endoscopy only in patients with persistent
      dysphagia, instead of a late barium study (> or = 21 days). OBD can then also be
      started earlier in these patients.

PMID- 23175923
TI  - Enhanced recovery after surgery (ERAS) protocol: prospective study of outcome in
      colorectal surgery.
AB  - BACKGROUND: Fast-track programs (ERAS) have been shown to improve postoperative
      recovery in colorectal surgery, combining newer anesthetic and minimally invasive
      surgery with evidence-based adjustments to facilitate revalidation. This
      prospective study evaluated the outcome of an ERAS protocol implementation in a
      university colorectal unit. METHODS: Between 2009 and 2010, 94 patients (49 males
      and 45 females) underwent an elective colorectal resection and were included in
      this protocol. All data were prospectively gathered in an electronic database. A
      cohort comparison was performed with 120 patients operated on in 2008 before ERAS
      implementation. RESULTS: The median age was 58 years [range: 29-76 years] and the
      median ASA score was 2. All colorectal procedures (85 sigmoid resections, 7 right
      hemicolectomies and 2 low anterior resections) were performed laparoscopically,
      with a conversion rate of 9,5%. Complications were noted in 14 patients (14,9%);
      two patients (2,1%) required a laparoscopic drainage of an infected hematoma
      during initial hospital stay. A significant (p < 0,001) reduced median
      postoperative hospital stay of 4 days [range : 2-11 days] in the ERAS group,
      compared with 6 days [range : 3-37] in the non fast-track group was noted. Early
      readmission occurred in five patients (5,3%) because of anastomotic leakage (n =
      2), ileus (n = 2) and a wound infection (n = 1). CONCLUSION: These results of
      length of stay, morbidity and readmission-rates have important implications for
      the organization of health care, waiting lists and costs. Therefore the ERAS
      principles should be more wide-spread implemented.

PMID- 23175924
TI  - "Diagnostic value of MRCP in biliary pancreatitis: result of long-term follow
      up".
AB  - AIM: Magnetic resonance cholangiopancreatography (MRCP) has increasingly been
      used to evaluate the common bile duct. This study was to determine the role of
      MRCP instead of endoscopic retrograde cholangiopancreatography (ERCP) in the
      management of patients with acute biliary pancreatitis. METHODS: A total of 81
      patients with mild or moderate biliary pancreatitis who underwent MRCP and were
      treated in our department with selective ERCP between May 2001 and July 2007 were
      entered into a prospective database. RESULTS: MRCP was considered abnormal in 13
      patients. Ten patients underwent ERCP. Three patients did not undergo ERCP due to
      protocol violations. In nine patients, stone extraction was performed. The
      remaining patient who had dilatation of the CBD underwent ES. The false positive
      rate of MRCP was 10%. The median follow-up of overall patients was 36 months
      (range 23-99 months). The patients with normal MRCP had a median follow-up of
      39.5 months (range 23-99 months). During the follow-up period in the normal MRCP
      group, five patients were diagnosed with recurrent biliary pancreatitis, of which
      three underwent ERCP (7.4%). There was no disease-related mortality during this
      period. CONCLUSION: In conclusion, the use of MRCP in acute biliary pancreatitis
      is safe and may be recommended as a tool to aid in the selective use of ERCP.

PMID- 23175925
TI  - Neutrophil-lymphocyte ratio predicts graft patency following lower limb
      revascularisation.
AB  - BACKGROUND: Graft failure is a significant problem following lower limb
      revascularisation. We hypothesised that the neutrophil-lymphocyte ratio (NLR), a
      simple and inexpensive index of systemic inflammation, predicts graft failure.
      METHODS: Consecutive patients undergoing infra-inguinal bypass grafting were
      identified from a prospective database. All patients underwent routine graft
      surveillance using Duplex ultrasound. Potential predictors of graft failure
      (occlusion or ipsilateral amputation) were assessed in univariate and
      multivariate regression models. RESULTS: Of 126 patients, 79 had patent grafts at
      1 year. The only independent predictor of graft failure was the postoperative
      NLR. CONCLUSION: Post-operative NLR may be a simple, inexpensive means of
      focussing surveillance resources on patients at high-risk of graft failure. Its
      value needs to be confirmed in larger cohorts.

PMID- 23175926
TI  - Intraoperative ketorolac and bleeding after laparoscopic Roux-en-Y gastric by
      pass surgery.
AB  - BACKGROUND: The unspecific non-steroidal anti-inflammatory drug (NSAID) ketorolac
      is used during surgery as a single dose regimen to reduce immediate postoperative
      pain. Many studies have shown an increased risk of bleeding in patients treated
      with NSAIDs. We wanted to investigate whether intraoperative ketorolac
      administered at the end of surgery resulted in increased bleeding assessed by
      reduction in haemoglobin and need for blood transfusion. METHODS: This was a
      retrospective review including all patients undergoing laparoscopic Roux-en-Y
      gastric bypass in the period between January 1st and March 1st, 2010. Haemoglobin
      levels, time of surgery, fluid treatment and the need for blood transfusion or
      reoperation were registered. RESULTS: A total of 162 patients were operated in
      the given period. Of these, the first 47 received intraoperative ketorolac. For
      the remaining 115 patients, ketorolac was withdrawn. The reduction in haemoglobin
      in patients receiving intraoperative ketorolac was higher compared with the
      patients who did not receive ketorolac (-11.3(7.6) % vs. -8.4(6.4) %; p = 0.018).
      No significant difference was found between the two groups with respect of
      transfusion requirements (2 out of 47 patients in the ketorolac group versus 0
      patients out of 115 in the control group (p = 0.08)). CONCLUSIONS: Ketorolac
      given during surgery may increase the risk of postoperative haemorrhage after
      laparoscopic Roux-en-Y gastric by-pass.

PMID- 23175927
TI  - Single-incision versus conventional laparoscopic cholecystectomy: a case control
      study.
AB  - BACKGROUND: Single-incision laparoscopic surgery (SILS) is a minimally invasive
      technique which can be used for treatment of gallbladder disease. To evaluate our
      initial experience, patients treated with SILS cholecystectomy were compared with
      a comparable group of patients treated with a conventional four trocart technique
      (LC). METHODS: Between May 2009 and April 2010, 60 SILS cholecystectomies were
      performed. These patients were matched by Body Mass Index (BMI) with 60 cases of
      conventional LC. RESULTS: The operative time was significantly longer in the SILS
      group 55 min (range, 25-126 min) compared to 49 min (range, 28-75 min) for the LC
      group. Excluding the first 15 SILS cases the operative time became comparable to
      the conventional technique, with a mean operative time of 51 min (range, 25-90
      min). No patients were converted to open cholecystectomy. In the SILS group 3
      patients developed a wound infection, in the conventional LC group 2. CONCLUSION:
      SILS cholecystectomy seems to be a safe and feasible procedure when performed by
      an experienced laparoscopic surgeon. Complication rates are comparable to
      conventional LC. With a learning curve of around 10 to 15 procedures, operative
      times approach those of conventional LC.

PMID- 23175928
TI  - Spontaneous pneumothorax in children with osteosarcoma: report of three cases and
      review of the literature.
AB  - Spontaneous pneumothorax is a rare manifestation of primary lung cancer or
      metastasis. It is estimated that < 1% of all cases of spontaneous pneumothorax
      are tumor-associated and metastatic osteogenic or soft-tissue sarcomas are
      associated most commonly with pneumothorax especially in the setting of cytotoxic
      chemotherapy or radiotherapy. In this article, we report three pediatric cases
      with osteosarcoma that developed spontaneous pneumothorax during chemotherapy
      with a review of the literature. Two of them had lung metastasis at the time of
      the detection of pneumothorax and the remaining patient was found to have a
      bronchopleural fistula. SPx is an emergency situation and early diagnosis and
      management can improve prognosis and quality of life of the patient however the
      optimal management has yet to be determined.

PMID- 23175929
TI  - Endovascular treatment of a chronic contained ruptured abdominal aortic aneurysm.
AB  - CASE REPORT: We report a 69-year-old Caucasian male who presented with
      irreversible ischemia to the left foot. CT-scan showed, besides occlusion of both
      superficial femoral arteries, a chronic contained rupture of an abdominal aortic
      aneurysm. The aneurysm was excluded with a stent graft placed through a femoral
      approach in a semi-urgent procedure. CT-scans at 1, 3 and 6 months demonstrated
      continued exclusion of the aneurysm. Chronic ruptures are a rare but important
      subset of ruptured abdominal aortic aneurysms. CT-scan with contrast enhancement
      is the gold standard diagnosing technique. Treatment consists of prompt surgical
      intervention with endovascular repair being increasingly used as an alternative
      to an open surgical approach.

PMID- 23175930
TI  - Surgical treatment of a giant mesenteric fibromatosis mimicking a
      gastrointestinal stromal tumor: a case report and current treatment aspects.
AB  - Intra-abdominal fibromatosis (IAF), usually located at the mesenteric level, is a
      locally invasive tumor of fibrous origin. Although lacking the ability to
      metastasize, it has the tendency to recur. The case described here is a case of
      mesenteric fibromatosis with involvement of the bowel wall, which had the
      appearance of a gastrointestinal stromal tumor (GIST), a tumor with malignant
      behavior. This report outlines the fact that certain non-typical cases of IAF
      with involvement of the bowel wall can be misdiagnosed as GIST. It is of outmost
      importance to make an early and correct diagnosis in such equivocal cases, so
      that the appropriate treatment can be closed.

PMID- 23175931
TI  - Gallstone ileus in a patient with Crohn's disease: a case report.
AB  - Gallstone ileus is a rare complication of cholelithiasis. Only 0,3-0,5% of all
      patients with gallstones will eventually suffer from this condition. It is well
      known that there is an increased prevalence of gallstones among patients with
      Crohn's disease, but gallstone ileus remains even in these patients an unfrequent
      condition. Because of the rarity of this disease and its presentation as an
      intestinal (sub)obstruction, mostly without biliary symptoms, diagnosis and
      surgical treatment are often delayed. We report the case of a 75-year-old woman
      with a long history of Crohn's disease presenting with intermittent symptoms of
      intestinal obstruction since several weeks. Symptoms were thought to be due to
      recurrence of Crohn's disease, but the patient did not respond to steroid
      therapy. Resection of the diseased ileocolic segment was performed and a large
      impacted stone was detected proximal of the stenotic segment. With this case
      report we want to emphasize how easily diagnosis of gallstone ileus can be
      missed, especially in Crohn's patients and we would like to discuss the different
      treatment options.

PMID- 23175932
TI  - Case report: a gastric lipoma in a morbid obese man.
AB  - We report a case of a 54-year-old, morbid obese man who presented with melena,
      hematemesis and fatigue over the last two days. The cause of this upper
      gastrointestinal bleeding was found on endoscopy which revealed an ulcerated
      submucosal mass in the gastric antrum. The haemorrhagia could not be stopped with
      injection of Aethoxysclerol. The mass was resected by an antrectomy with Roux-en
      Y reconstruction. Histologic examination showed a lipoma. No further treatment
      was necessary. In this case report, we would like to stress the need for
      histologic diagnosis to differentiate a benign gastric lesion from a malign.

PMID- 23175933
TI  - From ants to staples: history and ideas concerning suturing techniques.

PMID- 23175934
TI  - Prebiotics and low dose synbiotics for severe acute pancreatitis: time for a
      reappraisal?

PMID- 23175935
TI  - Study: hospitals struggle to implement proven strategies for eliminating ED
      boarding, crowding.
AB  - A new study suggests that proven strategies for eliminating boarding and crowding
      in the ED are being left on the table in many hospitals because leadership has
      not stepped forward to eliminate pockets of resistance. Further, there is new
      evidence that changes in practice intensity in the ED are contributing to
      crowding even though some of these changes were designed to do the opposite.
      Strategies that can ease crowding include smoothing out the schedule for elective
      procedures, moving boarded patients up to the hallways on inpatient floors, and
      appointing a bed czar to oversee bed utilization hospital-wide. Experts say such
      strategies are difficult to implement because they are hospital-level rather than
      ED-level problems. A new emphasis on physician satisfaction surveys is driving ED
      practice intensity along with changes in billing practices and technological
      innovations.

PMID- 23175936
TI  - Slash diversion, improve care of boarded patients with an ED-based hospital
      medicine (HMED) team.
AB  - To cut down on diversion time, Denver Health Medical Center in Denver, CO,
      decided to locate a hospital medicine team in its ED (HMED). The HMED team
      focuses on streamlining patient flow as well as caring for patients boarded in
      the ED. The approach has proven successful, slashing diversion by 27% while also
      increasing discharges from the ED by 61%, according to a pre and post study of
      the intervention. The HMED team includes a hospitalist and an allied health
      professional who are both housed in the ED during the daytime shift, from 7 a.m.
      to 5 p.m. The HMED team spends 75% of its time taking care of admitted patients
      who are boarded in the ED, and 25% of its time working on patient flow. Emergency
      department physicians say having immediate access to an admitting team
      streamlines the admitting process and helps to ensure that patients are sent to
      the most appropriate floors for care. A successful HMED intervention requires
      commitment to the approach from hospitalists, and a willingness among ED staff to
      have a hospitalist team located in the department, according to hospital sources.
      A productive relationship between ED physicians and hospitalists is key.

PMID- 23175937
TI  - The Joint Commission reports high interest in new certification program for
      Comprehensive Stroke Centers.
AB  - Hospitals with the advanced resources and personnel capable of providing state-of
      the-art care for the most complex types of stroke can now seek certification from
      The Joint Commission (TJC) as a Comprehensive Stroke Center. The move follows
      recommendations by the Brain Attack Coalition, an expert panel that established
      criteria for Comprehensive Stroke Centers. The concept is designed to strengthen
      a network of stroke care in the country similar to the system in place for trauma
      care. The certification process includes a two-day, on-site evaluation by TJC
      reviewers. Experts anticipate that about 200 medical centers will become
      certified as Comprehensive Stroke Centers. Comprehensive Stroke Centers should
      serve as referral centers for the more than 900 Primary Stroke Centers as well as
      other hospitals that are not equipped to care for complex stroke patients.

PMID- 23175938
TI  - "Yes board" facilitates rapid sharing of key data, trims LOS in the ED by 40
      minutes.
AB  - A practicing emergency medicine physician who is also a computer engineer has
      helped Mayo Clinic sites in Rochester, MN, and Phoenix, AZ, develop a web-based
      ED monitoring system that is responsive to the needs of clinicians. Data suggest
      that the innovation, called a Yes Board, has sliced LOS by as much as 40 minutes,
      and it is constantly being tweaked with changes and new functionality. Data flows
      automatically into the Yes Board from as many as 15 different data systems the
      hospital is already using. The Yes Board conveys the status of tests and
      procedures, clinical results, vital sign information, and where patients are in
      the admissions or discharge process.

PMID- 23175939
TI  - Smile.

PMID- 23175940
TI  - Growing up with type 2.

PMID- 23175941
TI  - Common cold remedies.

PMID- 23175942
TI  - Pumped up.

PMID- 23175943
TI  - Diabetes by the numbers.

PMID- 23175944
TI  - Sex and diabetes.

PMID- 23175945
TI  - A season of celebrations.

PMID- 23175946
TI  - Season's eatings.

PMID- 23175947
TI  - Guests in the gut.

PMID- 23175948
TI  - Poverty, marriage timing, and transitions to adulthood in Nepal.
AB  - This study examines the influence of household poverty during early childhood on
      schooling, workforce participation, and early marriage among adolescent girls in
      Nepal. Longitudinal data from the two-wave panel of the Nepal Living Standards
      Survey (NLSS) were used to examine these relationships. For 5-9-year-old girls
      contacted in NLSS I and again when aged 13-17 in NLSS II (N = 400), multinomial
      logit regression estimates indicate that household poverty during early childhood
      is associated with greater likelihood of marrying early or joining the workforce
      rather than remaining in school. Analyzing the data by household wealth quintiles
      reveals that these associations are largest for the second-poorest quintile, not
      the poorest. This study highlights the role of household rather than individual
      characteristics in adolescent girls' decisionmaking.

PMID- 23175949
TI  - Effects of birth spacing on maternal, perinatal, infant, and child health: a
      systematic review of causal mechanisms.
AB  - This systematic review of 58 observational studies identified hypothetical causal
      mechanisms explaining the effects of short and long intervals between pregnancies
      on maternal, perinatal, infant, and child health, and critically examined the
      scientific evidence for each causal mechanism hypothesized. The following
      hypothetical causal mechanisms for explaining the association between short
      intervals and adverse outcomes were identified: maternal nutritional depletion,
      folate depletion, cervical insufficiency, vertical transmission of infections,
      suboptimal lactation related to breastfeeding-pregnancy overlap, sibling
      competition, transmission of infectious diseases among siblings, incomplete
      healing of uterine scar from previous cesarean delivery, and abnormal remodeling
      of endometrial blood vessels. Women's physiological regression is the only
      hypothetical causal mechanism that has been proposed to explain the association
      between long intervals and adverse outcomes. We found growing evidence supporting
      most of these hypotheses.

PMID- 23175951
TI  - Family planning outcomes and primary school attendance in sub-Saharan Africa.
AB  - This study examines the relationship between women's family planning outcomes and
      primary school enrollment among their 8-11-year-old children. We analyze
      household- and wider-context-level data for 103,000 children in 30 sub-Saharan
      African countries. Negative associations with school enrollment are found for
      those who have short preceding or succeeding birth intervals, a young sibling, or
      a mother who is pregnant. These findings remain unchanged after controlling for
      socioeconomic and demographic characteristics. Analysis of interaction effects
      shows that many associations with family planning outcomes depend on the context
      in which the household is living, revealing the importance of a situation
      specific approach. Findings indicate that helping families improve their
      pregnancy planning will increase children's schooling opportunities and lead to
      more effective use of household and community resources.

PMID- 23175950
TI  - Migration experience and premarital sexual initiation in urban Kenya: an event
      history analysis.
AB  - Migration during the formative adolescent years can affect important life-course
      transitions, including the initiation of sexual activity. In this study, we use
      life history calendar data to investigate the relationship between changes in
      residence and timing of premarital sexual debut among young people in urban
      Kenya. By age 18, 64 percent of respondents had initiated premarital sex, and 45
      percent had moved at least once between the ages of 12 and 18. Results of the
      event history analysis show that girls and boys who move during early adolescence
      experience the earliest onset of sexual activity. For adolescent girls, however,
      other dimensions of migration provide protective effects, with greater numbers of
      residential changes and residential changes in the last one to three months
      associated with later sexual initiation. To support young people's ability to
      navigate the social, economic, and sexual environments that accompany residential
      change, researchers and policymakers should consider how various dimensions of
      migration affect sexual activity.

PMID- 23175952
TI  - Effectiveness of interventions designed to prevent female genital
      mutilation/cutting: a systematic review.
AB  - Female genital mutilation/cutting (FGM/C) is widely considered a human rights
      infringement, although communities that practice the tradition view it as an
      integral part of their culture. Given these vastly different views, the
      effectiveness of efforts to abandon FGM/C is uncertain. We conducted a systematic
      review of the best available evidence regarding evaluations of interventions to
      prevent FGM/C, including eight controlled before-and-after studies with 7,042
      participants from Africa. Findings indicate that 19 of 49 outcomes (with baseline
      similarity) were significantly different at study level, mostly favoring the
      intervention, but results from four meta-analyses showed considerable
      heterogeneity. The limited effectiveness and weak overall quality of the evidence
      from the studies appear related to methodological limitations of the studies and
      shortcomings in the implementation of the interventions. Nevertheless, the
      findings point to possible advantageous developments from the interventions.

PMID- 23175953
TI  - Malawi 2010: results from the demographic and health survey.

PMID- 23175954
TI  - Rwanda 2010: results from the demographic and health survey.

PMID- 23175955
TI  - Determination and confirmation of parent and total ractopamine in bovine, swine,
      and turkey tissues by liquid chromatography with tandem mass spectrometry: First
      Action 2011.23.
AB  - A candidate method selected by the AOAC Expert Review Panel (ERP) for Ractopamine
      for determination and confirmation of parent and total ractopamine by LC/MS/MS
      was validated in a single laboratory for bovine, swine, and turkey tissues. The
      candidate method utilizes methanol extraction of the tissues, followed by an
      optional enzymatic hydrolysis for determination of total (parent plus conjugate)
      ractopamine. A mixed-mode cation exchange SPE cartridge is used to purify the
      initial extract before LC/MS/MS. Matrix-matched standards and a ractopamine-d6
      internal standard are used for quantification of parent and total ractopamine in
      unknown samples. Validation data demonstrated that mean intertrial recoveries for
      ractopamine across all concentrations tested ranged from 79.7 to 102.2% for
      parent ractopamine and from 79.0 to 100.0% when a hydrolysis step was included.
      Intertrial repeatability precision ranged from 2.44 to 11.1% for parent
      ractopamine and 4.97 to 15.0% with hydrolysis. Estimated LOD values were below
      0.1 ng/g and LOQ values were validated at 0.25x the maximum residue limits. The
      data satisfy the requirements of the AOAC Stakeholder Panel for Veterinary Drug
      Residue Methods for single laboratory validation studies. The method was awarded
      Official Methods of Analysis First Action 2011.23 by the AOAC ERP on Veterinary
      Drug Residues.

PMID- 23175956
TI  - Methods of pesticide residue analysis.

PMID- 23175957
TI  - Review of sample preparation techniques for the analysis of pesticide residues in
      soil.
AB  - This paper reviews the sample preparation techniques used for the analysis of
      pesticides in soil. The present status and recent advances made during the last 5
      years in these methods are discussed. The analysis of pesticide residues in soil
      requires the extraction of analytes from this matrix, followed by a cleanup
      procedure, when necessary, prior to their instrumental determination. The
      optimization of sample preparation is a very important part of the method
      development that can reduce the analysis time, the amount of solvent, and the
      size of samples. This review considers all aspects of sample preparation,
      including extraction and cleanup. Classical extraction techniques, such as
      shaking, Soxhlet, and ultrasonic-assisted extraction, and modern techniques like
      pressurized liquid extraction, microwave-assisted extraction, solid-phase
      microextraction and QuEChERS (Quick, Easy, Cheap, Effective, Rugged, and Safe)
      are reviewed. The different cleanup strategies applied for the purification of
      soil extracts are also discussed. In addition, the application of these
      techniques to environmental studies is considered.

PMID- 23175958
TI  - Applications of solid-phase microextraction for the analysis of pesticide
      residues in fruits and vegetables: a review.
AB  - This paper reviews the application of various modes of solid-phase
      microextraction (SPME) for the analysis of pesticide residues in fruits and
      vegetables. SPME is a simple extraction technique that eliminates the use of
      solvent, and it is applied for the analysis of both volatile and nonvolatile
      pesticides. SPME has been successfully coupled to both GC and LC. The coupling
      with GC has been straightforward and requires little modification of existing
      equipment, but interfacing with LC has proved challenging. The external standard
      calibration technique is widely used for quantification, while standard addition
      and internal or surrogate standards are mainly used to account for matrix
      effects. All parameters that affect the extraction of pesticide residues from
      fruits and vegetables, and therefore need to be optimized, are also reviewed.
      Details of the characteristics of analytical procedures and new trends in fiber
      production using sol-gel technology and molecularly imprinted polymers are
      discussed.

PMID- 23175959
TI  - Analytical methodology for the determination of organochlorine pesticides in
      vegetation.
AB  - Due to the extensive use of organochlorine pesticides (OCPs) for agricultural
      purposes and their high persistence and low biodegradability, they have become an
      important group of contaminants. Detection and quantification of pesticide
      residues in food, particularly fruits and vegetables, is of growing concern for
      producers, consumers, and governments. The most widely used pretreatment for the
      extraction of pesticides in plants is based on solvent extraction liquid-solid
      extraction (LSE). LSE can be carried out using Soxhlet, shake-flask,
      homogenization, sonication, and, more recently, microwave-assisted extraction,
      pressurized liquid extraction, and supercritical fluid extraction. Furthermore,
      new analytical procedures using the extraction with sorbents, such as solid-phase
      microextraction, stir bar sorptive extraction, and matrix solid-phase dispersion,
      have also been used. On the other hand, a wide range of cleanup methods (liquid
      liquid extraction, solid-phase extraction, gel permeation chromatography, and
      dispersive solid-phase extraction; and chromatographic techniques with electron
      capture detector and mass spectrometry detector; and HPLC with a ultraviolet
      detector are reported in the literature. This article reviews the applicability,
      advantages, and disadvantages of various sample preparation techniques
      (traditional and new techniques) for the analysis of OCPs in different plants and
      plant materials. It covers more than 15 years of published methods in which
      pesticide residues have been determined in a wide range of vegetation samples
      (fruits, horticultural samples, medicinal plants, tree leaves, etc.) by the use
      of chromatographic techniques after various sample preparation steps. A great
      number of applications in different plant material are provided. To the best of
      the authors' knowledge, previously published reviews have not covered as wide and
      exhaustive range of vegetation matrixes as presented here. A summary of pesticide
      levels cited in the literature is included.

PMID- 23175960
TI  - Effects of temperature and purity of magnesium sulfate during extraction of
      pesticide residues using the QuEChERS method.
AB  - Despite its many documented advantages, the QuEChERS (Quick, Easy, Cheap,
      Effective, Rugged, and Safe) sample preparation approach has problems with a few
      unstable pesticides, partly due to the exothermic reaction generated by the use
      of anhydrous magnesium sulfate (anh. MgSO4) during extraction. These pesticides
      also tend to be difficult to analyze by GC/MS. The aim of this study was to
      evaluate the effect of temperature during the extraction process in a revised
      version of AOAC Official Method 2007.01 using anh. MgSO4 > or = 99% (fine powder)
      or > or = 97% (granular) purity, and the use of an ice bath for particular
      unstable pesticides of interest (chlorothalonil, captan, captafol, folpet, and
      the degradation products cis-1,2,3,6-tetrahydrophthalimide and phthalimide).
      Recoveries of 38 representative pesticides were measured in limes and broccoli at
      different extraction conditions by LC/MS/MS and low-pressure GC/MS/MS. Results
      showed that the difference in temperature when using > or = 99% versus > or = 97%
      purity anh. MgSO4 was 6-9 degrees C, which did not lead to significant
      differences in recoveries. The use of an ice bath aided recovery for some of the
      analytes in broccoli, but no significant differences were observed for limes,
      which already provided greater stability of the base-sensitive analytes due to
      acidity of the matrix.

PMID- 23175961
TI  - Multiresidue pesticide analysis of tuber and root commodities by QuEchERS
      extraction and ultra-performance liquid chromatography coupled to tandem mass
      spectrometry.
AB  - A simple, rapid, and reliable multiresidue method to determine 84 pesticides in
      potato and carrot samples by ultra-performance liquid chromatography coupled to
      MS/MS has been developed and fully validated for routine analysis according to
      ISO/IEC 17025:2005. The method makes use of a buffered Quick, Easy, Cheap,
      Effective, Rugged, and Safe (QuEChERS) sample preparation procedure based on a
      single extraction with acidified acetonitrile, followed by partitioning with
      salts. Chromatographic conditions were optimized in order to achieve a rapid
      separation in the multiple reaction monitoring mode. Performance characteristics
      of the method, including an estimation of measurement uncertainty using
      validation data, are reported for both matrixes. Calibration curves were linear
      from 0.010 to 0.150 mg/kg for most compounds. The LOD and LOQ were 0.006 and
      0.010 mg/kg, respectively, except for fluorocloridone, fluquinconazol, and
      hexitiazox, which were 0.030 and 0.050 mg/kg, respectively. Recoveries obtained
      were in the range 70-116%, with intraday precision values < or = 20% RSD and
      interday precision values < or = 25% RSD at two different concentration levels.
      The overall uncertainty of the method was estimated at two concentrations as
      being lower than 34% in all cases. The method has been applied to the analysis of
      70 vegetable samples, and imidacloprid and linuron were the pesticides most
      frequently found in potato and carrot commodities, respectively.

PMID- 23175962
TI  - Liquid-solid sample preparation followed by headspace solid-phase microextraction
      determination of multiclass pesticides in soil.
AB  - This paper describes development and validation of a multiresidue method for the
      determination of five pesticides (terbufos, prochloraz, chloridazon,
      pendimethalin, and fluorochloridone) belonging to different pesticide groups in
      soil samples by GC/MS, followed by its application in the analysis of some
      agricultural soil samples. The method is based on a headspace solid-phase
      microextraction method. Microextraction conditions, namely temperature,
      extraction time, and NaCI content, were tested and optimized using a 100 microm
      polydimethylsiloxane fiber. Three extraction solvents [methanol, methanol-acetone
      (1 + 1, v/v), and methanol-acetone-hexane (2 + 2 + 1, v/v/v)] and the optimum
      number of extraction steps within the sample preparation stage were optimized for
      the extraction procedure. LOD values for all the studied compounds were less than
      12 microg/kg. Recovery values for multiple analyses of soil samples fortified at
      30 microg/kg of each pesticide were higher than 64%. The method was proven to be
      repeatable, with RSD lower than 15%.

PMID- 23175963
TI  - Investigating the potential of metal-organic framework material as an adsorbent
      for matrix solid-phase dispersion extraction of pesticides during analysis of
      dehydrated Hyptis pectinata medicinal plant by GC/MS.
AB  - Metal-organic frameworks aluminum terephthalate MIL-53 and Cu-benzene-1,3,5
      tricarboxylate (BTC) were tested for extraction of pyrimethanil, ametryn,
      dichlofluanid, tetraconazole, flumetralin, kresoximmethyl, and tebuconazole from
      the medicinal plant Hyptis pectinata, with analysis using GC/MS in the selected
      ion monitoring mode. Experiments carried out at different fortification levels
      (0.1, 0.5, and 1.0 microg/g) resulted in recoveries in the range 61 to 107% with
      RSD values between 3 and 12% for the metal-organic framework materials. Detection
      and quantification limits ranged from 0.02 to 0.07 and 0.05 to 0.1 microg/g,
      respectively, for the different pesticides studied. The method developed was
      linear over the range tested (0.04-20.0 microg/g), with correlation coefficients
      ranging from 0.9987 to 0.9998. Comparison of MIL-53 and Cu-BTC with C18-bonded
      silica showed good performance of the MIL-53 metal-organic framework as a sorbent
      for the pesticides tested.

PMID- 23175964
TI  - Application of magnetic nanoparticles to residue analysis of organochlorine
      pesticides in water samples by GC/MS.
AB  - This paper describes a novel magnetic-SPE method for the determination of
      organochlorine pesticides (OCPs) in environmental water samples by use of Fe3O4
      magnetic nanoparticles (MNPs) coated with oleic acid followed by GC/MS. The
      chemisorption of oleic acid onto Fe3O4-MNPs provides reusability of the developed
      sorbent materials several times. The effects of different parameters such as pH,
      desorption solvent, contact time, temperature, ionic strength, and sorbent dosage
      on the efficiency of magnetic-SPE were investigated. The optimized SPE method
      involved shaking 50 mL of water sample (pH 4) with 50 mg oleic acid coated Fe3O4(
      ) MNPs for 1 h, isolating the sorbent with an Nd-Fe-B magnet, and eluting the
      OCPs with methanol. An ionic strength of 0.1 M and temperature of 15 degrees C
      provided the maximum extraction efficiency. The LOQs were in the range of 0.006
      to 0.048 microg/L. For three fortification levels, recoveries were in the range
      of 44-108%, with RSD <5%. The developed SPE method was successfully applied to
      real water samples, and it is viable, rapid, and easy to use for analysis of OCPs
      in water samples.

PMID- 23175965
TI  - Determination of azole fungicides in atmospheric samples collected in the
      Canadian prairies by LC/MS/MS.
AB  - An LC/MS/MS method has been developed for the determination of azole fungicides
      in the atmosphere at low pg/m3 concentrations. Detection limits in the range of
      0.16 to 1.2 pg/m3 for a weekly air sample were obtained for the 31 fungicides
      analyzed. This work represents the first detection of propiconazole,
      prothioconazole-desthio, and trace levels of hexaconazole in gas phase
      atmospheric samples collected in a Canadian agricultural region. Samples were
      collected during April-October 2010 at Bratt's Lake, Saskatchewan, in the
      Canadian prairies where there was known historical use of selected azole
      fungicides. Atmospheric concentrations were above detection limits only during
      June-August 2010, with maximum concentrations occurring in July at 77.9 and 37.5
      pg/m3 for propiconazole and prothioconazole-desthio, respectively. Gas phase
      atmospheric concentrations of propiconazole and prothioconazole-desthio increased
      following a spring and early summer with higher than normal daily precipitation.
      These azole fungicides showed the largest gas phase concentrations during periods
      of lower temperature and during sampling events with at least 1 day with no
      precipitation. The higher atmospheric gas phase concentrations of each azole
      fungicide were observed on different days, indicating different formulations may
      be in use in the prairie agricultural region.

PMID- 23175966
TI  - Application of RP-HPLC-diode array detector after SPE to the determination of
      pesticides in pepper samples.
AB  - The application of HPLC-diode array detector (DAD) after SPE for identification
      and quantitative analysis of pesticides in red and green pepper samples is
      demonstrated. An HPLC procedure on an RP column (C18) was developed for analysis
      of selected pesticides from different chemical groups: metamitron, metalaxyl,
      linuron, and prometryn. Average recoveries for C18 Polar Plus cartridges and
      solvents by the proposed RP-HPLC-DAD method after SPE are presented. Average
      recoveries from the spiked samples and the SDs were 22.5 +/- 2.2, 138.0 +/- 4.1,
      78.6 +/- 2.8, and 109.2 +/- 2.3% for metamitron, metalaxyl, linuron, and
      prometryn, respectively, at concentrations of 7 microg/g in the plant material.
      The efficiency of the SPE procedure was evaluated using real food samples. The
      quantities of prometryn, linuron, metalaxyl, and metamitron determined were in
      the ranges of 0.02-2.24 microg/g (n = 24), 0.08-1.01 microg/g (n = 9), 1.61-2.28
      microg/g (n=4), and 0.05-1.07 microg/g (n = 3), respectively, in plant material
      sampled in 2011. The method was validated for precision, repeatability, and
      accuracy.

PMID- 23175967
TI  - Hydrophilic interaction liquid chromatography and per aqueous liquid
      chromatography in fungicides analysis.
AB  - The goal of the study was to investigate the retention mechanism of selected
      fungicides in hydrophilic interaction liquid chromatography (HILIC) and per
      aqueous liquid chromatography (PALC). Chromatographic measurements were made on
      four physicochemically diversified HILIC columns, which were evaluated for the
      analysis of nine biologically active compounds, such as strobilurins and
      triazoles. The effects of the operating conditions on separations were
      investigated, including the concentration of the organic solvent in the aqueous
      organic (acetonitrile) mobile phase. The results were compared, and it was shown
      that two different retention mechanisms dominate in PALC at low acetonitrile
      concentrations and in HILIC at high acetonitrile concentrations.

PMID- 23175968
TI  - Determination of organophosphorus and carbamate insecticides in fresh fruits and
      vegetables by high-performance thin-layer chromatography-multienzyme inhibition
      assay.
AB  - HPTLC-enzyme inhibition assay was applied to different fruit and vegetable
      samples after individual spiking with organophosphate and carbamate pesticides at
      their maximum residue limits documented by the European Commission. Samples were
      extracted according to the QuEChERS (Quick, Easy, Cheap, Effective, Rugged, and
      Safe) method, including cleanup by primary secondary amine sorbent. Additional
      cleanup was performed on the HPTLC plate by a prechromatographic step to separate
      most coextracted matrix compounds from 20 different pesticides under study. With
      both rabbit liver esterase and cutinase from Fusarium solani pisi as enzyme
      sources, mean recoveries from apples, cucumbers, grapes, nectarines, plums,
      tomatoes, and lemons were in the ranges 86-109, 95-129, 96-114, and 90-111% for
      chlorpyrifos, paraoxon, parathion, and pirimicarb, respectively, with a mean RSD
      of 8.5% for all samples.

PMID- 23175969
TI  - Analytical and toxicological studies of decomposition of insecticide parathion
      after gamma-irradiation and ozonation.
AB  - The decomposition of the widely used organophosphorus pesticide parathion was
      carried out in aqueous solutions by the use of gamma-irradiation from a 60Co
      source or ozonation by means of an ozone generator, and by combined processes of
      ozonation and radiolysis. Factors affecting the parathion decomposition as well
      formation and decomposition of the main by-products, including irradiation dose,
      length of ozonation time, and presence of common scavengers, were investigated.
      The most efficient was found to be the gamma-irradiation process combined with a
      short ozonation period; about 1 kGy irradiation dose was sufficient to decompose
      the pesticide in 15 mg/L solutions. Chemical studies of the decomposition of
      parathion were accompanied by monitoring of toxicity changes of irradiated
      solutions with the Microtox test.

PMID- 23175970
TI  - Determination of direct available phosphate in fertilizers by a discrete
      analyzer: single-laboratory validation.
AB  - To improve throughput during peak seasonal demand, a screening method for the
      determination of fertilizer-available phosphate using a discrete analyzer for
      semi-automation was validated in a single laboratory. The fertilizer materials
      were extracted using a neutral EDTA-ammonium citrate solution as detailed in AOAC
      Official Method 993.31. Phosphate was subsequently freed from the matrix and
      converted to orthophosphate using an alkaline persulfate digestion modified from
      a U.S. Geological Survey water method. Phosphorus was determined colorimetrically
      on a discrete analyzer. Twelve check samples from the Magruder Fertilizer Check
      Sample Program and Association of Fertilizer and Phosphate Chemists Fertilizer
      Check Program were used for method validation experiments. The proposed method is
      linear from 0.01 to 20 mg/L (ppm) phosphorus. Recovery for all materials averaged
      101%, with a range of 99.2 to 103%. Bias for all materials averaged 0.59% with a
      range of -0.11 to 1.68%, with bias increasing at concentrations of available
      phosphate exceeding 40%. The LOD was calculated to be 0.001% available phosphate
      and the LOQ 0.002% available phosphate. The method was found fit for purpose as a
      screening method for available phosphate analysis in fertilizers.

PMID- 23175971
TI  - Determination of ash in animal feed: AOAC official method 942.05 revisited.
AB  - AOAC Official Method 942.05, Ash in Animal Feed, has been applied in feed
      laboratories since its publication in the Official Methods of Analysis in 1942.
      It is a routine test with renewed interest due to the incorporation of "ash
      values" into modern equations for the estimation of energy content of dairy feed,
      beef feed, and pet food. As with other empirical methods, results obtained are a
      function of the test conditions. For this method, the critical conditions are the
      ignition time, ignition temperature, and any other furnace or weighing
      conditions. Complete ignition can be observed by the absence of black color (due
      to residual carbonaceous material) in the ash residue. To investigate performance
      of AOAC 942.05, 15 samples were chosen to be representative of a wide range of
      feed materials. These materials were tested at the conditions of AOAC 942.05
      (ignition at 600 degrees C for 2 h) and similar or more rigorous conditions. The
      additional conditions investigated included: 600 degrees C for 4 h; 600 degrees C
      for 2 h, cool, and ignite 2 additional h; 600 degrees C for 2 h, cool, wet, dry,
      and ignite 2 additional h; 550 degrees C for 6 h; 550 degrees C for 3 h, cool,
      and ignite 3 additional h; and 550 degrees C for 3 h, cool, wet, dry, ignite 3
      additional h. Results for all other conditions investigated were found to be
      significantly different from the current AOAC Method 942.05. All ignition
      conditions were significantly different from each other except two: 550 degrees C
      for 3 h, cool, ignite 3 additional h; and 550 degrees C for 3 h, cool, wet, dry,
      and ignite 3 additional h. Recommendations for modification to AOAC Official
      Method 942.05 are suggested based on statistical analysis of the data and a
      review of the literature.

PMID- 23175972
TI  - Quantitative determination of alkaloids from roots of Hydrastis canadensis L. and
      dietary supplements using ultra-performance liquid chromatography with UV
      detection.
AB  - Ultra-performance liquid chromatography (UPLC) with UV detection was used for the
      quantification of alkaloids from roots of Hydrastis canadensis L. (goldenseal)
      and dietary supplements claiming to contain goldenseal. The analysis was
      performed on a Waters Acquity UPLC system with an Acquity UPLC BEH Shield RP18
      column using gradient elution with ammonium formate and acetonitrile containing
      formic acid. The chromatographic run time was less than 6 min. The detection
      wavelength used for beta-hydrastine and canadine was 290 nm; for hydrastinine,
      coptisine, jatrorrhizine, palmatine, and berberine, it was 344 nm. A total of
      five different extraction solvents, including 100% methanol, 90% methanol, 90%
      methanol + 1% acetic acid, 90% acetonitrile + 0.1% phosphoric acid, and 100%
      acetonitrile, were tested for recovery of the major compounds. The samples
      extracted with the 90% methanol + 1% acetic acid displayed the best recovery
      (>97%). The analytical method was validated for linearity, repeatability, LOD,
      and LOQ. The RSDs for intraday and interday experiments were less than 3.5%, and
      the recovery was 98-103%. UPLC/MS with a quadrupole mass analyzer and
      electrospray ionization source was used to confirm the identity of seven
      alkaloids. The analytical method was successfully applied to confirm the
      identification of seven alkaloids from the roots of H. canadensis, dietary
      supplements that claimed to contain goldenseal, and possible adulterant species.

PMID- 23175973
TI  - Quantification of chlorogenic acid and hyperoside directly from crude blueberry
      (Vaccinium angustifolium) leaf extract by NMR spectroscopy analysis: single
      laboratory validation.
AB  - A single-laboratory-validated NMR spectroscopy method was established for
      determining the quantity of chlorogenic acid and hyperoside from crude extract
      material of blueberry leaves of the species Vaccinium angustifolium var.
      laevifolium House. The calibration curve of chlorogenic acid showed a highly
      linear regression, R = 0.99998. NMR spectroscopy identification and
      quantification of the constituents directly from the mixture, within the error of
      HPLC-diode array detector analysis, were determined as 7.53 mM chlorogenic acid
      (64.0 mg chlorogenic acid/g powdered leaf) and 0.77 mM hyperoside (8.58 mg
      hyperoside/g powdered leaf). The LOD was calculated to be 0.01 mM and the LOQ
      0.01 mM by the 9 min and 13 s NMR spectroscopy experiment utilized. The assay
      showed no significant interference from different field strengths, extraction
      mesh size, gravimetric scale precision, NMR spectroscopy tube type, pulse
      program, amount of starting dry material, or day-to-day operation. The robustness
      of NMR spectroscopy as a means of definitively monitoring chlorogenic acid and
      hyperoside content directly from crude extracts was demonstrated by Youden
      statistical analysis.

PMID- 23175974
TI  - Spectrophotometric and stability-indicating high-performance liquid
      chromatographic determinations of terbutaline sulfate.
AB  - Spectrophotometric and stability-indicating HPLC procedures are described for
      determination of terbutaline sulfate in bulk powder and dosage form. The first
      procedure is based on diazo coupling of the phenolic groups of terbutaline
      sulfate with fast red B salt in the presence of sodium hydroxide. The colored
      compound developed in alkaline medium was measured at 475 nm. Different variables
      affecting the reaction were studied. Beer's Law is obeyed in the concentration
      range of 1-6 microg/mL. In the HPLC procedure, the separation was carried out on
      a Caltrex AIII column, a relatively new packing material consisting of silica
      bonded calix[8]arene, using an isocratic binary mobile phase, acetonitrile
      ammonium acetate (50 + 50, v/v), at pH 6.2. A diode array detector was used at
      280 nm. The method was validated for system suitability, linearity, precision,
      LOD, LOQ, specificity, stability, and robustness. The LOD and LOQ were 0.196 and
      0.781 microg/mL, respectively. The recovery values of this method were between 98
      and 102%, and the reproducibility was within 0.92%. Statistical comparison of the
      results obtained from the analysis of the studied drug to those of the official
      British Pharmacopoeia (2007) method using t- and F-tests showed no significant
      difference between them.

PMID- 23175975
TI  - Stress degradation studies on azithromycin and development of a validated
      stability-indicating TLC-densitometric method with HPLC/electrospray ionization
      MS analysis of degradation products.
AB  - The purpose of this work was to develop a sensitive stability-indicating TLC
      densitometric method for determination of azithromycin (AZ) in the presence of
      its impurities E, I, and L, and to study the stability of AZ under different
      stress conditions. The method was developed on TLC aluminum plates precoated with
      silica gel F254 using the mobile phase methanol-acetone-ammonia 25% (2+13+0.1,
      v/v/v), which gives compact zones for AZ (Rf= 0.39) and impurities E, I, and L
      (Rf = 0.54, 0.20, and 0.05, respectively). Densitometric analysis of AZ and its
      impurities was carried out at 483 nm after spraying with sulfuric acid-ethanol (1
      + 4, v/v) and heating at 100 degrees C for 5 min. The linear regression analysis
      data for the calibration plots showed good linear relationships with r = 0.9941
      for AZ, 0.9987 for impurity E, 0.9989 for impurity I, and 0.9984 for impurity L.
      AZ was subjected to acidic and alkaline hydrolysis, oxidation, and reduction
      stress. The drug underwent degradation under these conditions. The degradation
      products were well-resolved from the pure drug, with significantly different Rf
      values. A plausible degradation pathway of AZ was established by
      HPLC/electrospray ionization-MS analysis of the products.

PMID- 23175976
TI  - Evaluation of the VITEK 2 gram positive (GP) microbial identification test card:
      collaborative study.
AB  - A collaborative study was conducted to evaluate the performance of the VITEK 2
      Gram Positive (GP) identification card for use with the VITEK 2 automated
      microbial identification system. The GP test card is used in the identification
      of selected Gram positive organisms, including Listeria and Staphylococcus
      species. The VITEK 2 GP card is based on 43 biochemical tests measuring carbon
      source utilization, inhibition and resistance, and enzymatic activities. A total
      of 20 laboratories representing government, industry, and private testing
      laboratories throughout the United States participated. In this study, 720 Gram
      positive inclusivity isolates were analyzed by the GP Identification method. Of
      the 720 well-characterized isolates, 714 were identified correctly, zero were
      misidentified, zero were unidentified, and six were not characterized as a Gram
      positive organism by the VITEK 2 GP method. Additionally, 120 strains exclusive
      of Gram-positive organisms were screened by Gram stain. A total of 106 isolates
      were correctly excluded. Fourteen organisms were incorrectly characterized by
      Gram stain procedures, thus resulting in improper analysis and misidentification
      by VITEK GP. The VITEK 2 GP identification method is an acceptable automated
      method for the rapid identification of selected Gram-positive bacteria.

PMID- 23175977
TI  - The interlaboratory performance of microbiological methods for food analysis.
AB  - Repeatability and reproducibility data for microbiological methods in food
      analysis were collated and assessed with a view to identifying useful or
      important trends. Generalized additive modeling for location, shape, and scale
      was used to model the distribution of variances. It was found that mean
      reproducibility for log10(CFU) data is largely independent of concentration,
      while repeatability SD of log10(CFU) data shows a strongly significant decrease
      in repeatability SD with increasing enumeration. The model for reproducibility SD
      gave a mean of 0.44, with an upper 95th percentile of approximately 0.76.
      Repeatability variance could be described reasonably well by a simple dichotomous
      model; at enumerations below 10(5)/g, the model for repeatability SD gave a mean
      of approximately 0.35 and upper 95th percentile of 0.63. Above 10(5)/g, the model
      gave a mean of 0.2 and upper 95th percentile of 0.36. A Horwitz-like function
      showed no appreciable advantage in describing the data set and gave apparently
      worse fit. The relationship between repeatability and reproducibility of
      log10(CFU) is not constant across the concentration range studied. Both
      repeatability and reproducibility were found to depend on matrix class and
      organism.

PMID- 23175978
TI  - Validation of the Legipid bioalarm Legionella assay.
AB  - Legipid Bioalarm Legionella is a test based on combined magnetic immunocapture
      and enzyme-immunoassay (CEIA) for the detection of Legionella pneumophila in
      water. Anti-L. pneumophila antibodies are immobilized on magnetic microspheres.
      Immunomagnetic analysis is applied to preconcentrated water samples in a final
      test volume of 9 mL. The method was compared with the standard culture method on
      both spiked and naturally contaminated water samples. The test was evaluated in
      potable, industrial, and natural water matrixes, according to the scope of the
      ISO 11731 reference method. These waters were tested with the target at levels
      ranging from low (10-99 CFU/mL) to high (100-999 CFU/mL); a Chi-square value of
      1.8 indicated that there was no significant difference between the test and the
      reference method. The false-positive rate was 7%, and the false-negative rate 2%.
      For the inclusivity study, all 17 strains of L. pneumophila of different
      serogroups reacted with the test. For the exclusivity study, 17 strains of other
      Legionella species and 16 non-Legionella strains were tested. There were no cross
      reactions with non-Legionella strains. L. beliardensis, L. adelaidensis, and one
      environmentally isolated Legionella sp. produced a positive result at high
      concentrations of 1800, 230, and 3900 CFU/mL, respectively. Agreement between the
      two methods was 95.9%.

PMID- 23175979
TI  - Recovery of Salmonella from internally and externally contaminated whole tomatoes
      using several different sample preparation procedures.
AB  - Studies were conducted to determine the relative effectiveness of whole soak
      [current Bacteriological Analytical Manual-(BAM) Salmonella method], quarter,
      stomach, and blend methods for the recovery of Salmonella organisms from
      internally and externally contaminated tomatoes. Tomatoes were subjected to three
      inoculation methods: surface inoculation, internal inoculation by injection, and
      immersion with single Salmonella serovars. The inoculation levels ranged from 1
      to 100 CFU/tomato for surface and injection inoculation or 1 to 100 CFU/mL for
      immersion inoculation. Tomatoes were held for 3 days after inoculation at 2-6
      degrees C prior to initiation of analysis. Contaminated tomatoes were soaked,
      quartered, stomached, and blended in appropriate portions of Universal Pre
      enrichment broth, and incubated for 24 h at 35 +/- 2 degrees C. The BAM
      Salmonella culture method was followed thereafter, and tomatoes were treated as a
      low-microbial-load food. The stomaching procedure was significantly (P < 0.05)
      more effective than the whole soak procedure for recovery of internalized
      Salmonella from tomatoes (by injection). The blending procedure was
      arithmetically superior to the stomaching procedure for detection of internalized
      Salmonella from tomatoes (by immersion). The blending procedure showed the same
      effectiveness as the whole soak procedure for the detection of Salmonella on
      tomato surfaces. Comparisons between test portion-to-broth ratios (weight to
      volume) showed that a 1:3 test portion-to-broth ratio had a better buffering
      capacity for blended tomatoes than a 1:1 test portion-to-broth ratio. It is
      recommended that the current whole soak BAM tomato sample preparation procedure
      be replaced with a blending procedure and a 1:3 test portion-to-broth ratio.

PMID- 23175980
TI  - Evaluating the use of fatty acid profiles to differentiate human pathogenic and
      nonpathogenic Listeria species.
AB  - Listeria monocytogenes is a Gram-positive human pathogen that is responsible for
      serious infections in immunocompromised individuals and pregnant women. Because
      of recent epidemics caused by food contaminated with L. monocytogenes, rapid
      methods for the detection of this pathogen in food are of interest. Capillary gas
      chromatography with flame ionization detection (GC-FID) was used to determine the
      cellular fatty acid profiles of six species of Listeria. The six different
      species are L. monocytogenes, L. ivanovii, L. innocua, L. welshimeri, L.
      seeligeri, and L. grayi. For GC-FID analysis, whole cell fatty acid methyl esters
      (FAMEs) from cells cultured on brain heart infusion (BHI) agar at 35 degrees C
      for 24 h were obtained by saponification, methylation, and extraction into
      hexane/methyl tert-butyl ether. A preliminary data set for 15 strains of Listeria
      species was prepared using fatty acid profiles from two or three replicates
      prepared on different days. Major fatty acids of the Listeria strains evaluated
      in this study were C15:0 iso, C15:0 ante iso, C16:0 iso, C16:0, C17:0 iso, and
      C17:0 ante iso. All of the major fatty acids differ significantly among these six
      species. The two fatty acids C17:0 ante iso and C15:0 ante iso showed the highest
      percentages, and the ratio of the two clearly showed significant differences
      between the human pathogen L. monocytogenes and the five nonpathogenic species.
      Analysis of FAMEs from Listeria strains grown on BHI agar by a GC-FID method is a
      sensitive procedure for identification of these organisms and differentiation
      between pathogenic and nonpathogenic species.

PMID- 23175981
TI  - QuickTox kit for QuickScan aflatoxin.
AB  - The QuickTox Kit for QuickScan Aflatoxin uses lateral flow technology and a
      reader-based system for quantitative determination of total aflatoxins. The
      performance of this assay was examined using corn samples naturally contaminated
      with aflatoxins in internal and independent laboratory evaluations and was judged
      against previously established acceptance criteria. Performance was evaluated for
      linearity, selectivity, matrix, robustness, and stability experiments. All data
      points in these studies fell within the ranges defined in the acceptance
      criteria. The assay exhibits linear dose response over the range tested, 0-100
      ppb, with R2 values exceeding 0.98. RSDr values for results ranged from 4.7 to
      17.7% across all tested levels. The four major aflatoxin types in corn are
      detected in the assay, with highest sensitivity for the most prevalent type, B1.
      Assay results are unaffected by the presence of other common mycotoxins.
      Robustness studies co-varied assay timing (-20%, 60% compared to the standard
      assay), temperature (18-30 degrees C), and sample volume (+/- 20% compared to the
      standard assay). Judged against the acceptance criteria, results were unaffected
      by these changes. The QuickTox Kit for QuickScan Aflatoxin assay is a user
      friendly and reliable method for determination of total aflatoxins.

PMID- 23175982
TI  - Analysis of free and total myo-inositol in foods, feeds, and infant formula by
      high-performance anion exchange chromatography with pulsed amperometric
      detection, including a novel total extraction using microwave-assisted acid
      hydrolysis and enzymatic treatment.
AB  - A method for the analysis of free and total myo-inositol in foods, feeds, and
      infant formulas has been developed and validated using high-performance anion
      exchange chromatography with pulsed amperometric detection. The option of a free
      myo-inositol determination or a complete total myo-inositol determination from
      main bound sources can be achieved. These sources include phytates,
      lower'phosphorylated forms, and phosphatidylinositol. This approach gives the
      option for subtraction of myo-inositol from nonbioavailable sources when it is
      quantified using other methods if a total bioavailable myo-inositol result is
      desired for nutritional labeling of a product. The free analysis was validated in
      a milk-based infant formula, giving RSD(R) of 2.29% and RSD, of 2.06%. A mean
      recovery of 97.9% was achieved from various spike levels of myo-inositol.
      Certified National Institute of Standards and Technology reference material
      verified the method's compatibility and specificity. Two different total analyses
      were validated in a soy-based infant formula and compared. One technique involved
      using a conventional acid hydrolysis with autoclave incubation for 6 h, while the
      other used a novel technique of microwave-assisted acid hydrolysis with enzymatic
      treatment that can minimize extraction to 1 day. The autoclave analysis had
      RSD(R) of 2.08% and RSDr of 1.55%, along with a mean spike recovery of 102.1% at
      various myo-inositol spike levels. The microwave/enzyme total analysis had RSD(R)
      of 4.34% and RSD, of 4.70%, along with a mean spike recovery of 104.2% at various
      spike levels of myo-inositol. Main sources of myo-inositol including phytic acid
      and phosphatidylinositol were tested with both total analyses. Mean recoveries of
      phytic acid and phosphatidylinositol through the autoclave total analysis were
      90.4 and 98.3%, respectively. Mean spike recoveries for these same sources in soy
      based infant formula through the microwave/enzyme total analysis were 97.2 and
      96.3%, respectively. Comparison of soy-based infant formula and corn grain
      samples with high levels of these main sources showed in similar results,
      indicating both total analyses are acceptable for use. An additional glycerol
      kinase step was also developed to remove glycerol from the chromatographic
      elution window of myoinositol in samples with high levels of glycerol.

PMID- 23175983
TI  - Microwave-assisted extraction and quantitative LC/ID-MS measurement of total
      choline and free carnitine in food standard reference materials.
AB  - The Stakeholder Panel on Infant Formula and Adult Nutritionals of AOAC
      INTERNATIONAL has declared both choline and carnitine to be priority nutrients in
      infant formulas, and ongoing efforts exist to develop or improve Official Methods
      of Analysis for these nutrients. As a result, matrix-based certified reference
      materials are needed with assigned values for these compounds. In this work,
      traditional acid and enzymatic hydrolysis procedures were compared to microwave
      assisted acid hydrolysis, and conditions optimized to provide complete sample
      hydrolysis and recovery of total choline from four food standard reference
      materials (SRMs): whole milk powder, whole egg powder, infant formula, and soy
      flour. The extracts were analyzed using LC on a mixed-mode column (simultaneous
      RP and ion exchange) with isotope dilution-MS detection to achieve simultaneous
      quantification of total choline and free carnitine. Total choline has been
      determined in these four food matrixes with excellent precision (0.65 to 2.60%)
      and accuracy, as confirmed by use of SRM 1849 Infant/Adult Nutritional Formula as
      a control material. Free carnitine has been determined in two of these food
      matrixes with excellent precision (0.69 to 2.19%) and accuracy, as confirmed by
      use of SRM 1849 Infant/Adult Nutritional Formula as a control material.
      Limitations in simultaneous determination of total choline and free carnitine
      resulted from extreme differences in concentration of the two components in egg
      powder and soy flour (at least three orders of magnitude). Samples required
      dilution to prevent poor LC peak shape, which caused decreased precision in the
      determination of low concentrations of free carnitine. Despite this limitation,
      the described method yields results comparable to current AOAC Official Method
      999.14 Choline in Infant Formula, with a decrease of more than 2 h in sample
      preparation time.